PMID- 22035590 TI - Cortical peroxynitration of nerve growth factor in aged and cognitively impaired rats. AB - Basal forebrain cholinergic neurons (BFCN), a system involved in learning and memory processes, are highly dependent on a continuous supply of biologically active nerve growth factor (NGF). Age-related cholinergic atrophy and cell loss in normal brains is apparently not complemented by reductions in the levels of NGF as could be expected. In the present work, cortical proNGF/NGF were immunoprecipitated from cortical brain homogenates from young and aged and behaviorally characterized rats and resolved with antinitrotyrosine antibodies to reveal nitration of tyrosine residues in proteins. Cortical proNGF in aged and cognitively impaired rats was found to be a target for peroxynitrite-mediated oxidative damage with correlative impact on decrease in choline acetyltransferase activity. These studies provide evidence for oxidative stress damage of NGF molecules in the cerebral cortex of cognitively impaired aged rats as previously shown in AD human brains. PMID- 22035591 TI - Glycosaminoglycans from aged human hippocampus have altered capacities to regulate trophic factors activities but not Abeta42 peptide toxicity. AB - Glycosaminoglycans (GAGs) are major extracellular matrix components known to tightly regulate cell behavior by interacting with tissue effectors as trophic factors and other heparin binding proteins. Alterations of GAGs structures might thus modify the nature and extent of these interactions and alter tissue integrity. Here, we studied levels and composition of GAGs isolated from adult and aged human hippocampus and investigated if their changes can influence the function of important trophic factors and the Abeta42 peptide toxicity. Biochemical analyses showed that heparan sulfates are increased in the aged hippocampus. Moreover, GAGs from aged hippocampus showed altered capacities to regulate trophic factor activities without changing their capacities to protect cells from Abeta42 toxicity, compared to adult hippocampus GAGs. Structural alterations in GAGs from elderly were suggested by differential transcripts levels of key biosynthetic enzymes. C5-epimerase and 2-OST expressions were decreased while NDST-2 and 3-OST-4 were increased; in contrast, heparanase expression was unchanged. Results suggest that alteration of GAGs in hippocampus of aged subjects could participate to tissue impairment during aging. PMID- 22035592 TI - Rescue of cognitive aging by long-lasting environmental enrichment exposure initiated before median lifespan. AB - The rescue of cognitive function through environmental enrichment (EE) during aging has been extensively documented. However, the age at onset, the duration of EE, and the cerebral mechanisms required to obtain the greatest benefits still remain to be determined. We have recently shown that EE applied for 3 mo after the median lifespan, i.e., the age at which 50% of the population is still alive (from 17 to 20 mo in NMRI mice), failed to prevent cognitive deficits in senescent animals. In the present study, mice were exposed to EE prior to the median lifespan, and for a longer total duration (from 14 to 20 mo), before the assessment of memory performance and the electrophysiological properties of hippocampal neuronal networks. The EE prevented memory deficits and reduced anxiety as the animal aged. Moreover, EE attenuated the age-related impairment of basal glutamatergic neurotransmission in CA1 hippocampal slices, and reversed the decrease in isolated N-methyl-D-Aspartate receptor (NMDA-R)-dependent synaptic potentials. Surprisingly, EE did not prevent the age-related alteration of theta burst-induced long-term potentiation (LTP). This study therefore suggests that EE needs to be initiated before the age corresponding to the median lifespan and/or required long duration (> 3 mo) to have an effect on cognitive aging. In addition, we show that EE probably acts through theta-burst-independent mechanisms of synaptic plasticity. PMID- 22035594 TI - Characterization of iron-phosphate-silicate chemical garden structures. AB - Chemical gardens form when ferrous chloride hydrate seed crystals are added or concentrated solutions are injected into solutions of sodium silicate and potassium phosphate. Various precipitation morphologies are observed depending on silicate and phosphate concentrations, including hollow plumes, bulbs, and tubes. The growth of precipitates is controlled by the internal osmotic pressure, fluid buoyancy, and membrane strength. Additionally, rapid bubble-led growth is observed when silicate concentrations are high. ESEM/EDX analysis confirms compositional gradients within the membranes, and voltage measurements across the membranes during growth show a final potential of around 150-200 mV, indicating that electrochemical gradients are maintained across the membranes as growth proceeds. The characterization of chemical gardens formed with iron, silicate, and phosphate, three important components of an early earth prebiotic hydrothermal system, can help us understand the properties of analogous structures that likely formed at submarine alkaline hydrothermal vents in the Hadean-structures offering themselves as the hatchery of life. PMID- 22035595 TI - Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. AB - The goal of the study was to determine the association between diabetes and inflammation in clinically diagnosed diabetes patients. We hypothesized that low grade inflammation in diabetes is associated with the level of glucose control. Using a cross-sectional design we compared pro- and anti-inflammatory cytokines in a community-recruited cohort of 367 Mexican Americans with type 2-diabetes having a wide range of blood glucose levels. Cytokines (IL-6, TNF-alpha, IL 1beta, IL-8) and adipokines (adiponectin, resistin and leptin) were measured using multiplex ELISA. Our data indicated that diabetes as whole was strongly associated with elevated levels of IL-6, leptin, CRP and TNF-alpha, whereas worsening of glucose control was positively and linearly associated with high levels of IL-6, and leptin. The associations remained statistically significant even after controlling for BMI and age (p=0.01). The association between TNF alpha, however, was attenuated when comparisons were performed based on glucose control. Strong interaction effects between age and diabetes and BMI and diabetes were observed for IL-8, resistin and CRP. The cytokine/adipokine profiles of Mexican Americans with diabetes suggest an association between low-grade inflammation and quality of glucose control. Unique to in our population is that the chronic inflammation is accompanied by lower levels of leptin. PMID- 22035596 TI - Continuous controlled-infusion of hypertonic saline solution in traumatic brain injured patients: a 9-year retrospective study. AB - INTRODUCTION: Description of a continuous hypertonic saline solution (HSS) infusion using a dose-adaptation of natremia in traumatic brain injured (TBI) patients with refractory intracranial hypertension (ICH). METHODS: We performed a single-center retrospective study in a surgical intensive care unit of a tertiary hospital. Fifty consecutive TBI patients with refractory ICH treated with continuous HSS infusion adapted to a target of natremia. In brief, a physician set a target of natremia adapted to the evolution of intracranial pressure (ICP). Flow of NaCl 20% was a priori calculated according to natriuresis, and the current and target natremia that were assessed every 4 hours. RESULTS: The HSS infusion was initiated for a duration of 7 (5 to 10) (8 +/- 4) days. ICP decreased from 29 (26 to 34) (31 +/- 9) mm Hg at H0 to 20 (15 to 26) (21 +/- 8) mm Hg at H1 (P < 0.05). Cerebral perfusion pressure increased from 61 (50 to 70) (61 +/- 13) mm Hg at H0 up to 67 (60 to 79) (69 +/- 12) mm Hg at H1 (P < 0.05). No rebound of ICH was reported after stopping continuous HSS infusion. Natremia increased from 140 (138 to 143) (140 +/- 4) at H0 up to 144 (141 to 148) (144 +/- 4) mmol/L at H4 (P < 0.05). Plasma osmolarity increased from 275 (268 to 281) (279 +/- 17) mmol/L at H0 up to 290 (284 to 307) (297 +/- 17) mmol/L at H24 (P < 0.05). The main side effect observed was an increase in chloremia from 111 (107 to 119) (113 +/- 8) mmol/L at H0 up to 121 (117 to 124) (121 +/- 6) mmol/L at H24 (P < 0.05). Neither acute kidney injury nor pontine myelinolysis was recorded. CONCLUSIONS: Continuous HSS infusion adapted to close biologic monitoring enables long-lasting control of natremia in TBI patients along with a decreased ICP without any rebound on infusion discontinuation. PMID- 22035597 TI - Explaining the variability in recommended intakes of folate, vitamin B12, iron and zinc for adults and elderly people. AB - OBJECTIVE: To signal key issues for harmonising approaches for establishing micronutrient recommendations by explaining observed variation in recommended intakes of folate, vitamin B12, Fe and Zn for adults and elderly people. DESIGN: We explored differences in recommended intakes of folate, vitamin B12, Fe and Zn for adults between nine reports on micronutrient recommendations. Approaches used for setting recommendations were compared as well as eminence-based decisions regarding the selection of health indicators indicating adequacy of intakes and the consulted evidence base. RESULTS: In nearly all reports, recommendations were based on the average nutrient requirement. Variation in recommended folate intakes (200-400 MUg/d) was related to differences in the consulted evidence base, whereas variation in vitamin B12 recommendations (1.4-3.0 MUg/d) was due to the selection of different CV (10-20 %) and health indicators (maintenance of haematological status or basal losses). Variation in recommended Fe intakes (men 8-10 mg/d, premenopausal women 14.8-19.6 mg/d, postmenopausal women 7.5-10.0 mg/d) was explained by different assumed reference weights and bioavailability factors (10-18 %). Variation in Zn recommendations (men 7-14 mg/d, women 4.9-9.0 mg/d) was also explained by different bioavailability factors (24-48 %) as well as differences in the consulted evidence base. CONCLUSIONS: For the harmonisation of approaches for setting recommended intakes of folate, vitamin B12, Fe and Zn across European countries, standardised methods are needed to (i) select health indicators and define adequate biomarker concentrations, (ii) make assumptions about inter-individual variation in requirements, (iii) derive bioavailability factors and (iv) collate, select, interpret and integrate evidence on requirements. PMID- 22035598 TI - Effectiveness and use of linezolid in hospitalisation wards. AB - OBJECTIVE: To describe the use and effectiveness of linezolid as an alternative treatment for methicillin-resistant Staphylococcus aureus. METHOD: Demographic, clinical and safety data were collected from hospitalised patients. The information sources were the clinical records and the pharmacy programme. RESULTS: Thirty patients were treated with linezolid (median age 69.3, 63% male). The median duration of treatment was 8 days. The most prevalent indication was soft tissues and skin infections (46.7%). The indications were off-label in 40% of cases. Linezolid was used as a targeted therapy in 53%, especially for coagulase-negative Staphylococcus. Clinical healing occurred in 83.3%, and microbiological healing in 40%. Three patients (10%) experienced side effects from using linezolid. CONCLUSION: The effectiveness and safety of linezolid is similar to that described in the trials. Its off-label use and the high number of empirical treatments mean that new strategies must be developed. PMID- 22035599 TI - Evaluation of negative outcomes associated with medication (NOM) by pharmacists at a home assistance programme in a Brazilian teaching hospital. AB - BACKGROUND: The concept of pharmaceutical care (PC) specifically refers to the pharmacist being able to identify, prevent and resolve negative outcomes associated with medication (NOM). According to the Third Consensus of Granada, these are patient health-related outcomes not consistent with pharmacotherapy objectives, and are associated with the proper or erroneous use of medicines. In this way, pharmacists might provide the pharmacist to provide the correct use of medicines to patients who are attended at home. OBJECTIVE: This study aimed to detect, classify and quantify NOM, according to the Third Consensus of Granada, in patients treated at home, who were assisted by the Home Assistance Programme of the University Hospital of University of Paulo, Brazil. METHOD: A descriptive, observational and cross-sectional study was conducted. The pharmacotherapy plan was filled during the interview with the patient or caregiver. RESULTS: The study included 87 patients with a mean age of 66 years old, adults (89%), children (11%), female (58%) and retired (62%). A total of 62% patients presented NOM, with an average of 1.13 NOM per patient. The NOM included untreated health problems (20.6%), effects from unnecessary medicines (9.1%), non-quantitative ineffectiveness (34.5%), quantitative ineffectiveness (3.4%), non-quantitative safety problems (11.4%) and quantitative safety problems (3.4%). Patients with the following characteristics were more prevalent than expected in the NOM effectiveness group: those aged between 65 and 74 years (p=0.0199), those with a low education level (p=0.0266), those with increased comorbidity (p=0.0461), those using medicine for the digestive tract and metabolism (p=0.0475) and those using medicine for blood and blood-forming organs (p=0.0466). For the NOM necessity group, patients with endocrine, nutritional and metabolic diseases (p=0.0587) were in greater numbers than expected; and for the NOM safety group, only patients aged over 74 years (p=0.01809) were in greater numbers. CONCLUSION: For this population, it was concluded that there were several factors related to the occurrence of NOM: age, education, number of comorbidities, use of medicines for the digestive tract and the metabolism and medicines for blood and blood forming organs. The use of the Third Consensus of Granada classification was very important for the recognition and measurement of NOM. PMID- 22035600 TI - Application of the Technology Web 2.0 in a drug information centre. AB - OBJECTIVE: To develop a Web 2.0 resource map and select those that may be useful in a Drug Information Centre at a Hospital Pharmacy Department (CIMSF). METHOD: A multidisciplinary working group under the Biomedical Information Commission selected some of the Web 2.0 resources included in the Guia d'usos i estil a les xarxes Socials guide of the Catalonian Government. RESULTS: Six resources were selected: Netvibes, Delicious, Google groups, Google Docs, Slideshare and Twitter. These tools were used for 5 months to manage biomedical information for the medical staff, and to provide external visibility by providing information to other health professionals. More than a thousand hits were recorded on the portal Netvibes and more than 100 professionals followed CIMSF on Twitter. CONCLUSIONS: The Web 2.0 offers useful, user-friendly and cost-efficient tools which could be implemented in a CIMSF, while also enabling participation in external networks of pharmacotherapeutic interest, increasing its visibility to other professionals. PMID- 22035601 TI - [Patent expiry for profitable drugs]. PMID- 22035604 TI - 1, 2, 3: counting the fingers on a chicken wing. AB - RNA-seq transcriptomics of digit primordia in the developing chick wing and leg has clarified a long-standing dispute between paleontologists and embryologists about evolutionary homology. PMID- 22035603 TI - Plasma biomarkers of oxidative stress and genetic variants in age-related macular degeneration. AB - PURPOSE: To compare plasma levels of oxidative stress biomarkers in patients with age-related macular degeneration (AMD) and controls and to evaluate a potential relationship between biochemical markers of oxidative stress and AMD susceptibility genotypes. DESIGN: Prospective case-control study. METHODS: Plasma levels of oxidative stress biomarkers were determined in 77 AMD patients and 75 controls recruited from a clinical practice. Cysteine, cystine (CySS), glutathione, isoprostane, and isofuran were measured, and participants were genotyped for polymorphisms in the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genes. RESULTS: CySS was elevated in cases compared with controls (P = .013). After adjustment for age, sex, and smoking, this association was not significant. In all participants, CySS levels were associated with the CFH polymorphism rs3753394 (P = .028) as well as an 8-allele CFH haplotype (P = .029) after correction for age, gender, and smoking. None of the other plasma markers was related to AMD status in our cohort. CONCLUSIONS: Our investigation of the gene-environment interaction involved in AMD revealed a relationship between a plasma biomarker of oxidative stress, CySS, and CFH genotype. These data suggest a potential association between inflammatory regulators and redox status in AMD pathogenesis. PMID- 22035605 TI - The effect of pre-pregnancy BMI on intention, initiation and duration of breast feeding. AB - OBJECTIVE: To determine whether pre-pregnancy BMI influences breast-feeding practice. DESIGN: Retrospective epidemiological study. SETTING: University Hospital Leuven, Catholic University Leuven, Belgium. SUBJECTS: Two hundred women (median age 29 years, interquartile range (IQR) 4; 52 % nulliparae) were grouped into four categories according to pre-pregnancy BMI using WHO cut-offs. RESULTS: The incidence of intention and initiation of breast-feeding was significantly lower in underweight (64 %) and obese women (68 %) compared with normal weight (92 %) and overweight women (80 %). Initiation was also related to parity (OR = 0.582; 95 % CI 0.400, 0.846), but not to gestational weight gain, method of delivery or hypertensive disorders. Fifty-two per cent of underweight, 70 % of normal weight and 56 % of overweight women were exclusively breast-feeding their infant during the first month of life. This incidence was significantly lower in the obese group (34 %; P = 0.030). Only 40 % of all infants were exclusively breast-fed at 3 months of age, with the lowest prevalence among women with obesity (P = 0.0 0 1). The median duration of any breast-feeding in the obese group (1.8 months, IQR 3.4) was significantly shorter than in the underweight (3.0 months, IQR 3.1), normal weight (3.0 months, IQR 2.4) and overweight group (3.0 months, IQR 3.5; P = 0.024). Reasons given for ceasing breast-feeding in the obese group were maternal complications (29 %), insufficient milk supply (23 %), sucking problems (21 %) and work resumption (21 %). CONCLUSIONS: Breast-feeding practice in the total population, but especially among women with obesity, fell short of global WHO recommended standards. Policy initiatives and local interventions should continue to support breast-feeding, but also prevent maternal obesity. PMID- 22035606 TI - Characterization of the novel HLA-C*16:07:02 allele in a family of Benin origin. AB - The novel allele HLA-C*16:07:02 differs from HLA-C* 16:07:01 by a silent nucleotide substitution at codon 220 (TAC -> TAT). PMID- 22035607 TI - Foreword. PMID- 22035608 TI - Pulmonary arterial hypertension. AB - Pulmonary hypertension is a complex and multidisciplinary disorder. The classification of pulmonary hypertension includes 5 groups. Pulmonary arterial hypertension is a rare disorder that can be idiopathic or heritable in nature, or associated with other conditions, such as scleroderma or congenital heart disease. The recent decades have realized advances in the treatment of this once devastating disease. More commonly, pulmonary hypertension is associated with other disorders, such as those that elevate left heart filling pressures and hypoxemic lung disease. Chronic thromboembolic disease can result in pulmonary hypertension. To determine the etiology, a thorough and methodical evaluation must be completed. Often, an echocardiogram is the first test to suggest the diagnosis of pulmonary hypertension. Studies to identify potential associated causes are important. The diagnostic evaluation culminates in right heart catheterization. Over recent years, advances in therapies, including the prostacyclins, the endothelin receptor antagonists, and the phosphodiesterase type 5 inhibitors, have resulted in an improved quality of life and outlook for patients with what is often a progressive disease. PMID- 22035609 TI - 7 billion of us. PMID- 22035610 TI - Multidrug-resistant Salmonella enterica. PMID- 22035611 TI - One health: moving from concept to reality. PMID- 22035612 TI - Urgent need for formal medical training in infectious diseases in India. PMID- 22035613 TI - HIV drug and supply stock-outs in Latin America. PMID- 22035614 TI - Integrated delivery of HIV and tuberculosis services in sub-Saharan Africa: a systematic review. AB - Tuberculosis is a major cause of morbidity and mortality in people with HIV and about a quarter of HIV-related deaths are attributed to tuberculosis. In this Review we identify and synthesise published evidence for the effectiveness and cost-effectiveness of eight integrated strategies recommended by WHO that represent coordinated delivery of HIV and tuberculosis services. Evidence supports concurrent screening for tuberculosis and HIV, and provision of either co-trimoxazole during routine tuberculosis care or isoniazid during routine HIV care and at voluntary counselling and testing centres. Although integration of antiretroviral therapy into tuberculosis care has shown promise for improving health outcomes for patients, evidence is insufficient to make conclusive claims. Evidence is also insufficient on the accessibility of condoms at tuberculosis facilities, the benefits of risk reduction counselling in patients with tuberculosis, and the effectiveness of tuberculosis infection control in HIV health-care settings. The vertical response to the tuberculosis and HIV epidemics is ineffective and inefficient. Implications for policy makers and funders include further investments in implementing integrated tuberculosis and HIV programmes with known effectiveness, preferably in a way that strengthens health systems; evaluative research that identifies barriers to integration; and research on integrated strategies for which effectiveness, efficiency, and affordability are not well established. PMID- 22035615 TI - Prevalence and implications of multiple-strain infections. AB - Infections frequently contain multiple strains (genotypes) of the same pathogen, yet they are still usually treated as uniform entities. In this Review, we discuss problems with inconsistent definition of the term "strain" and review the prevalence and implications of multiple-strain infections. Up to now, multiple strain infections have been shown unambiguously in 51 human pathogens (and 21 non human ones) and are likely to arise in most pathogen species. In human pathogens, multiple-strain infections usually reach considerable frequencies (median 11.3%, mean 21.7% of infections), which are certainly underestimated in many cases because of technical limitations of detection. For many diseases, the importance of multiple-strain infections is still unclear, but theoretical work and experimental results from animal models suggest a broad range of clinically relevant effects. Multiple-strain infections can affect host immune responses and our ability to prevent and treat infection efficiently. Competition and mutualism between strains change pathogen and disease dynamics and promote pathogen evolution. Co-infection enables gene transfer among strains. Taking multiple strain infections into account will improve our understanding of host-pathogen interactions and disease dynamics, and will provide a basis for novel control approaches. PMID- 22035617 TI - Pulsed-activated therapy. PMID- 22035618 TI - Lapidus arthrodesis. PMID- 22035620 TI - Editor's comments. PMID- 22035621 TI - Sinus tarsi artery. PMID- 22035623 TI - Methicillin-resistant Staphylococcus aureus arthritis in adults: case report and review of the literature. AB - OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) septic arthritis has emerged over the past 25 years as an increasingly prevalent and serious infection. We sought to characterize the clinical features of MRSA septic arthritis in adult patients. METHODS: We report a case of community-acquired fatal MRSA septic arthritis of the hip and analyze the clinical features of 56 additional adult patients with native-joint MRSA septic arthritis identified through a systematic literature review. RESULTS: Among 56 previously reported cases of MRSA native-joint septic arthritis, 42 were men, 14 had polyarticular infections, 5 were previously healthy individuals with community-acquired infections, and 8 had a fatal outcome. The most frequent predisposing factor was a preexisting rheumatologic condition. The knees and shoulders were most commonly affected. CONCLUSIONS: MRSA native-joint septic arthritis is a predominantly male disease that is usually nosocomial in origin but can occur rarely in health care naive patients. A preexisting rheumatic disease is the most common predisposition. Community-acquired MRSA septic arthritis can be fatal. Cultures should be performed promptly, to identify potential antibiotic resistance. Patients presenting with both community-acquired and nosocomial septic arthritis should receive initial antibiotic treatment that includes coverage for MRSA. PMID- 22035624 TI - Psychological factors affecting the outcome of total hip and knee arthroplasty: a systematic review. AB - OBJECTIVES: Recently, numerous studies have reported that psychological factors can influence the outcome of total knee arthroplasty (TKA) and total hip arthroplasty (THA). However, a systematic overview is missing. The objective of this study was to examine which psychological factors influence the outcome of TKA and THA and to what extent. METHODS: Data were obtained from the MEDLINE and EMBASE databases from inception to January 2011. Search terms included TKA and THA, outcome measures, and psychological aspects. Two reviewers independently selected the studies. Studies with a prospective before-after design with a minimum follow-up time of 6 weeks were included. One reviewer extracted the results and 2 reviewers independently conducted quality assessment. We distinguished between follow-up shorter and equal or longer than 1 year. RESULTS: Thirty-five of 1837 studies met the inclusion criteria and were included in this systematic review. In follow-ups shorter than 1 year, and for knee patients only, strong evidence was found that patients with pain catastrophizing reported more pain postoperatively. Furthermore, strong evidence was found that preoperative depression had no influence on postoperative functioning. In long-term follow-up, 1 year after TKA, strong evidence was found that lower preoperative mental health (measures with the SF-12 or SF-36) was associated with lower scores on function and pain. For THA, only limited, conflicting, or no evidence was found. CONCLUSIONS: Low preoperative mental health and pain catastrophizing have an influence on outcome after TKA. With regard to the influence of other psychological factors and for hip patients, only limited, conflicting, or no evidence was found. PMID- 22035625 TI - Central sensitization in patients with rheumatoid arthritis: a systematic literature review. AB - OBJECTIVE: The goal of the present study is to systematically review the scientific literature addressing central sensitization and central nociceptive processing in patients with rheumatoid arthritis (RA). METHODS: To identify relevant articles, we searched PubMed and Web of Science. The search strategy was a combination of terms of the following groups: "Rheumatoid arthritis," inflammatory joint pain, or arthritis; AND (central) sensitization, (central) hypersensitivity, central hyperexcitability, pain modulation, pain processing, neural inhibition, or pain physiopathology; AND pain, nociception, hyperalgesia, pain threshold, or algometry. Articles fulfilling the inclusion criteria were screened for methodologic quality with specific checklists to evaluate different study designs (2 independent raters). RESULTS: Twenty-four full-text articles were included, of which the majority were case-control studies, followed by nonsystematic reviews, cross-sectional studies, and case reports. Methodologic quality was very heterogeneous. Preliminary evidence for generalized hyperalgesia in RA is available. In addition, the mechanism behind impaired central nociceptive processing remains rather obscure. The role of cytokines and neuropeptides especially remains to be elucidated. Windup appears to develop more easily in RA, but evidence in support of impaired nociceptive inhibition and cognitive emotional sensitization (sensitization due to cognitive bias) is scarce. CONCLUSIONS: The symmetrical manifestation of the disease, the poor relation between disease activity and symptoms, and the generalized hyperalgesia at both articular and nonarticular sites for different kinds of stimuli are indicative of the presence of central sensitization in RA patients. Further research is required to provide firm evidence in support of various aspects of central sensitization in humans with RA. PMID- 22035626 TI - Subclinical atherosclerosis and endothelial dysfunction in patients with early rheumatoid arthritis as evidenced by measurement of carotid intima-media thickness and flow-mediated vasodilatation: an observational study. AB - OBJECTIVE: In this study, we aimed to investigate the frequency of endothelial dysfunction and subclinical atherosclerosis in early rheumatoid arthritis (RA) patients by carotid intima-media thickness (cIMT) and endothelial-dependent flow mediated vasodilatation (ED-FMD) as compared with healthy controls. METHODS: The study included 35 early RA patients (disease duration <12 months) and 35 healthy controls. Intima-media thickness of common carotid artery and ED-FMD of brachial artery were measured by high-resolution ultrasonography. Disease activity of RA was assessed by Disease Activity Score and activities of daily living were determined by Health Assessment Questionnaire-Disability Index Score. RESULTS: RA patients (age 38.3 +/- 10.6 years) had average disease duration of 0.46 +/- 0.28 years and 22 patients (62.9%) were rheumatoid factor (RF) positive (RF titer >9.56 IU/mL). There were no significant differences between age, sex, and lipid profiles of patient and control group. cIMT was significantly higher in RA patients (0.50 +/- 0.16 mm) than in controls (0.44 +/- 0.09 mm) (P = 0.007). Similarly, FMD% was significantly lower in RA patients [5.26 (2.9-10.6)] as compared with controls [10.34 (7.4-14.3)] (P = 0.004). Age, systolic blood pressure, tender joint count, and swollen joint count had significant correlations with patient cIMT. RF titer came out to be the major risk factor for increased cIMT of the patients. CONCLUSIONS: Compared with controls, early RA patients have higher cIMT and lower FMD%, denoting premature atherosclerosis. Our data suggest that early determination of FMD% and cIMT may be useful tools to assess cardiovascular risk even in early RA patients. PMID- 22035627 TI - High survivin levels predict poor clinical response to infliximab treatment in patients with rheumatoid arthritis. AB - OBJECTIVE: To evaluate if the measurement of survivin in the blood of patients with rheumatoid arthritis (RA) undergoing infliximab treatment has predictive value for treatment response. METHODS: The study included 87 consecutive RA patients (age 24-89 years, disease duration 18-526 months) treated with regular infusions of influximab. Survivin levels were measured by enzyme-linked immunosorbent assay and evaluated in relation to the total dose of infliximab, disease activity (DAS28), response to infliximab treatment (change in DAS28 >1.2), and radiographic damage (vdH-Sharp score). RESULTS: Thirty-seven percent of patients were survivin-positive (survivin >0.9 ng/mL) and showed severe radiographic damage at the start of infliximab treatment compared with survivin negative (P = 0.027). Patients with high survivin levels were unlikely to respond to infliximab treatment (OR 4.02 [1.22-14.61], P = 0.022) and achieve remission (OR 4.32[1.01-30.11], P = 0.048) compared with patients with low survivin levels. CONCLUSIONS: High survivin levels are associated with severe radiographic damage at the start of treatment and a poor response to infliximab. Survivin measurement should be considered an additional tool for aiding the selection and follow-up of antirheumatic treatment. PMID- 22035628 TI - Imaging approaches for evaluating peripheral joint abnormalities in juvenile idiopathic arthritis. AB - OBJECTIVES: To assess the usefulness of imaging studies for peripheral joint assessment in children with juvenile idiopathic arthritis (JIA), based on a systematic literature review. METHODS: We used PubMed to identify relevant articles published between 2000 and 2011. RESULTS: Plain radiography is still the reference imaging study for monitoring joint destruction in patients with JIA, and the results correlate well with the clinical findings. Radiographs should be obtained routinely during follow-up and in therapeutic trials. Available scoring methods have been validated in children, but no recommendations are available on the intervals between radiographic assessments. Ultrasonography and magnetic resonance imaging (MRI) can detect inflammatory changes that precede bone destruction. Ultrasonography features in JIA are still being studied. Ultrasonography can detect clinically silent synovitis, which has major implications for determining the JIA subtype. MRI is the only imaging study capable of showing bone marrow edema, which predicts joint destruction. CONCLUSIONS: Although radiography remains the reference standard imaging study for assessing peripheral joint destruction in JIA, ultrasonography and MRI allow the early detection of predestructive changes, the presence of which affects treatment decisions. Much more work is needed to determine the optimal imaging protocols, the best interval between imaging evaluations during follow-up, and the therapeutic implications of imaging study findings. PMID- 22035629 TI - A novel HLA-A*30 allele, HLA-A*30:36. AB - A novel HLA allele, HLA-A*30:36, is found in a donor from the Central German Bone Marrow Donor Registry. PMID- 22035630 TI - Platelet dysfunction in vascular pathologies and how can it be treated. AB - Cardiovascular diseases are one of the leading causes of morbidity and mortality in industrialized countries, and although many processes play a role in the development of vascular disease, thrombosis is the primary event that precipitates stroke and acute coronary syndromes. The blood platelets are of significant importance in medicine. These cells are involved in many physiological processes, particularly haemostasis through their ability to aggregate and form clots in response to activation. In addition, these dynamic cells display activities that extend beyond thrombosis, including an important role in initiating and sustaining vascular inflammation. The expansion of knowledge from basic and clinical research has highlighted the critical position of platelets in several inflammatory diseases such as arthritis and atherosclerosis. Platelets are emerging as important mediators of inflammation and provide important signals to mediate phenotype of other blood and vascular cells. The important role of platelets in arterial thrombosis and the onset of acute myocardial infarction after atherosclerotic plaque rupture make inhibition of platelet aggregation a critical step in preventing thrombotic events associated with stroke, heart attack, and peripheral arterial thrombosis. However, the use of platelet inhibitors for thrombosis prevention must seek a delicate balance between inhibiting platelet activation and an associated increased bleeding risk. The aim of this review is to up-date the knowledge on platelets physiology and dysfunction in pathologies, such as diabetes mellitus, hypercholesterolemia, and hypertension, emphasizing the link between platelets and the inflammation-related atherosclerosis. The review evaluates the opportunities offered by the novel platelet inhibitors to efficiently alleviate the thrombotic events. PMID- 22035631 TI - Heparin attenuates lipopolysaccharide-induced acute lung injury by inhibiting nitric oxide synthase and TGF-beta/Smad signaling pathway. AB - INTRODUCTION: Heparin, a potent blood anticoagulant, has been shown to exert a variety of pharmacological activities. The purpose of this study was to investigate whether heparin has a beneficial effect on lipopolysaccharide (LPS) induced acute lung injury (ALI) in rats and to further explore the possible underlying mechanisms. MATERIALS AND METHODS: Adult Sprague-Dawley rats were randomly assigned into the control, heparin, LPS, and LPS plus heparin groups. ALI was induced by intratracheal instillation of LPS at a dose of 1 mg/kg. Rats in the LPS plus heparin group were intravenously received 50 U/ kg heparin every 1 h after the induction of ALI. RESULTS: We found that heparin significantly improved LPS-induced lung pathological changes, inhibited myeloperoxidase (MPO) activity, and reduced malondialdehyde (MDA) level and lung wet/dry weight ratio. Heparin also inhibited the release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, and markedly decreased the expression of inducible nitric oxide synthase (iNOS) in lung tissues and thus prevented nitric oxide (NO) release in response to LPS challenge. Additionally, heparin decreased the expression of transforming growth factor-beta1 (TGF-beta1), p-Smad 2, and p-Smad 3, which are all important molecules of the TGF-beta1/Smad signaling pathway. CONCLUSIONS: Heparin significantly ameliorated the lung injury induced by LPS in rats via the inhibition of nitric oxide synthase expression and the TGF-beta/Smad pathway. Heparin may be a potential therapeutic reagent for treating ALI in the future. PMID- 22035632 TI - Circulating levels of thrombospondin-1 are decreased in HELLP syndrome. AB - BACKGROUND: Preeclampsia is characterised by an imbalance of circulating pro- and anti-angiogenic factors. The syndrome of haemolysis, elevated liver enzymes and low platelet count (HELLP) develops mostly on the ground of preeclampsia, and one of its important features is the severe disturbance of the coagulation system, intravascular coagulopathy. Thrombospondin-1 (TSP-1) is derived from the endothelium and platelets, and exerts potent pro-thrombotic and anti-angiogenic effects. Our aim was to determine, whether its circulating levels are altered in preeclampsia and in HELLP syndrome. METHODS: We enrolled 45 pregnant women with early-, 43 with late-onset preeclampsia, 21 with HELLP-syndrome, 45 with uncomplicated pregnancy and 20 non-pregnant controls in our case-control study. TSP-1 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Circulating TSP-1 levels were lower in HELLP syndrome compared to all other study groups, while they were unaltered in preeclampsia compared to the control groups. There was a significant positive linear correlation between TSP-1 levels and platelet count in HELLP syndrome. In patients with more severe HELLP syndrome, TSP-1 levels were significantly lower compared to women suffering from a milder form of HELLP syndrome. CONCLUSIONS: Circulating thrombospondin-1 levels are decreased in HELLP syndrome and they seem to reflect disease severity, lower levels representing a more severe state. Nevertheless, despite its potent anti angiogenic effect, our results suggest that circulating TSP-1 does not play a significant role in the pathogenesis of preeclampsia. PMID- 22035633 TI - Urinary excretion of iPF(2alpha)-III predicts the risk of future thrombotic events. A 10-year follow-up. PMID- 22035634 TI - Imaging for target volume delineation in rectal cancer radiotherapy--a systematic review. AB - The global move towards more conformal radiotherapy for rectal cancer requires better imaging modalities that both visualise the disease accurately and are reproducible; to reduce interobserver variation. This review explores the advances in imaging modalities used in target volume delineation, with a view to make recommendations for current clinical practice and to propose future directions for research. A systematic review was conducted using MEDLINE and EMBASE. Articles considered relevant by the authors were included. Planning with orthogonal films is being replaced by computed tomography (CT) simulation. This is now considered the 'gold standard' and allows conformal three-dimensional planning. Magnetic resonance imaging (MRI) has been shown to overcome some of the limitations of CT and can be used either as a diagnostic image to visually aid planning, or as a 'planning' MRI carried out in the treatment position and co registered with the planning CT. The latter approach has been shown to change the treated volumes compared with CT and in prostate cancer patients has been shown to reduce interobserver variation. There are remaining issues with four dimensional motion that are yet to be fully appreciated or overcome. 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography/CT co-registered with planning CT results in smaller volumes than CT alone and also reduces interobserver variation, but requires further validation before routine implementation. Experimental work utilising novel positron emission tomography tracers and diffusion-weighted MRI shows promise and requires further evaluation. Rigorous quality assurance is important with processing of newer imaging modalities. Further work needs to be conducted into both interobserver variation and the formal evaluation of the clinical benefits of newer imaging modalities. Developments in image-guided radiotherapy are also required to ensure that improvements in target definition at the planning stage are reproducible throughout treatment. PMID- 22035635 TI - Bailing out. PMID- 22035636 TI - Effect of dietary beta-agonist treatment, vitamin D3 supplementation and electrical stimulation of carcasses on colour and drip loss of steaks from feedlot steers. AB - In this study, 20 young steers received no beta-agonist (C) and 100 animals all received zilpaterol hydrochloride (Z), with 1 group receiving Z while the other 4 groups receiving Z and vitamin D(3) at the following levels (IU/animal/day) and durations before slaughter: 7million for 3days (3D7M) or 6days (6D7M), 7million for 6days with 7days no supplementation (6D7M7N) and 1million for 9days (9D1M). Left carcass sides were electrically stimulated (ES) and right sides not (NES). Samples were analysed fresh or vacuum-aged for 14days post mortem. Parameters included drip loss and instrumental colour measurements. In general, zilpaterol showed increased drip loss, lighter meat, and reduced redness. Vitamin D(3) supplementation could not consistently overcome these negative effects. All vitamin D(3) treatments reduced drip loss of stimulated aged steaks. PMID- 22035637 TI - [Systematic literature review on patient safety in medical departments]. AB - Patient safety is an issue of interest. All scenarios of health care have a risk of adverse events (AE) and determination of its incidence has been reported in virtually all medical specialties. OBJECTIVE: To determine the incidence reported in the medical literature of adverse events in medical departments. DESIGN AND METHODS: An exhaustive search of biomedical databases using different strategies, search in high impact journals and a manual search of related articles. RESULTS: We reviewed 17,437 entries. After reading the abstracts and articles, and applying previously defined inclusion and exclusion criteria, we selected 10 articles that reported the incidence of adverse events in medical departments. Most studies corresponded to a historical cohort, had used an AE screening to identify high risk patients, and had used a structured review to check clinical records. None of them had as their ultimate objective to report on the impact of adverse events or characterize them. The incidence reported in medical departments ranged from 3.6% to 21.7%. The definitions of adverse events and forms of detection were similar; however the few differences put the comparability at risk. CONCLUSION: No studies were aimed at quantifying or characterising the adverse events in health care. None of them defined what constitutes a medical department, although the results reported are within the published values for health systems. Further research is needed in this area. PMID- 22035638 TI - Limitations to maximum sprinting speed imposed by muscle mechanical properties. AB - It has been suggested that the force-velocity relationship of skeletal muscle plays a critical limiting role in the maximum speed at which humans can sprint. However, this theory has not been tested directly, and it is possible that other muscle mechanical properties play limiting roles as well. In this study, forward dynamics simulations of human sprinting were generated using a 2D musculoskeletal model actuated by Hill muscle models. The initial simulation results compared favorably to kinetic, kinematic, and electromyographic data recorded from sprinting humans. Muscle mechanical properties were then removed in isolation to quantify their effect on maximum sprinting speed. Removal of the force-velocity, excitation-activation, and force-length relationships increased the maximum speed by 15, 8, and 4%, respectively. Removal of the series elastic force-extension relationship decreased the maximum speed by 26%. Each relationship affected both stride length and stride frequency except for the force-length relationship, which mainly affected stride length. Removal of all muscular properties entirely (optimized joint torques) increased speed (+22%) to a greater extent than the removal of any single contractile property. The results indicate that the force velocity relationship is indeed the most important contractile property of muscle regarding limits to maximum sprinting speed, but that other muscular properties also play important roles. Interactions between the various muscular properties should be considered when explaining limits to maximal human performance. PMID- 22035639 TI - Pulsatile extracorporeal circulation during on-pump cardiac surgery enhances aortic wall shear stress. AB - Controversy on superiority of pulsatile versus non-pulsatile extracorporeal circulation in cardiac surgery still continues. Stroke as one of the major adverse events during cardiopulmonary bypass is, in the majority of cases, caused by mobilization of aortic arteriosclerotic plaques that is inducible by pathologically elevated wall shear stress values. The present study employs computational fluid dynamics to evaluate the aortic blood flow and wall shear stress profiles under the influence of antegrade or retrograde perfusion with pulsatile versus non-pulsatile extracorporeal circulation. While, compared to physiological flow, a non-pulsatile perfusion resulted in generally decreased blood velocities and only moderately increased shear forces (48 Pa versus 20 Pa antegradely and 127 Pa versus 30 Pa retrogradely), a pulsatile perfusion extensively enhanced the occurrence of turbulences, maximum blood flow speed and maximum wall shear stress (1020 Pa versus 20 Pa antegradely and 1178 Pa versus 30 Pa retrogradely). Under these circumstances arteriosclerotic embolism has to be considered. Further simulations and experimental work are necessary to elucidate the impact of our findings on the scientific discourse of pulsatile versus non pulsatile extracorporeal circulation. PMID- 22035640 TI - Design of next generation total disk replacements. AB - To improve the treatments for low back pain, new designs of total disk replacement have been proposed. The question is how well these designs can act as a functional replacement of the intervertebral disk. Four finite element models were made, for four different design concepts, to determine how well they can mimic the physiological intervertebral disk mechanical function. The four designs were a homogenous elastomer, a multi-stiffness elastomer, an elastomer with fiber jacket, and a hydrogel with fiber jacket. The best material properties of the four models were determined by optimizing the model behavior to match the behavior of the intervertebral disk in flexion-extension, axial rotation, and lateral bending. It was shown that neither a homogeneous elastomer nor a multi stiffness elastomer could mimic the non-linear behavior within the physiological range of motion. Including a fiber jacket around an elastomer allowed for physiological motion in all degrees of freedom. Replacing the elastomer by a hydrogel yielded similar good behavior. Mimicking the non-linear behavior of the intervertebral disk, in the physiological range of motion is essential in maintaining and restoring spinal motion and in protecting surrounding tissues like the facet joints or adjacent segments. This was accomplished with designs mimicking the function of the annulus fibrosus. PMID- 22035641 TI - The oscillatory behavior of the CoM facilitates mechanical energy balance between push-off and heel strike. AB - Humans use equal push-off and heel strike work during the double support phase to minimize the mechanical work done on the center of mass (CoM) during the gait. Recently, a step-to-step transition was reported to occur over a period of time greater than that of the double support phase, which brings into question whether the energetic optimality is sensitive to the definition of the step-to-step transition. To answer this question, the ground reaction forces (GRFs) of seven normal human subjects walking at four different speeds (1.1-2.4 m/s) were measured, and the push-off and heel strike work for three differently defined step-to-step transitions were computed based on the force, work, and velocity. To examine the optimality of the work and the impulse data, a hybrid theoretical empirical analysis is presented using a dynamic walking model that allows finite time for step-to-step transitions and incorporates the effects of gravity within this period. The changes in the work and impulse were examined parametrically across a range of speeds. The results showed that the push-off work on the CoM was well balanced by the heel strike work for all three definitions of the step to-step transition. The impulse data were well matched by the optimal impulse predictions (R(2)>0.7) that minimized the mechanical work done on the CoM during the gait. The results suggest that the balance of push-off and heel strike energy is a consistent property arising from the overall gait dynamics, which implies an inherited oscillatory behavior of the CoM, possibly by spring-like leg mechanics. PMID- 22035642 TI - A novel strategy to develop therapeutic approaches to prevent proliferative vitreoretinopathy. AB - Proliferative vitreoretinopathy (PVR) thwarts the repair of rhegmatogenous retinal detachments. Currently, there is no effective prevention for PVR. Platelet-derived growth factor receptor alpha (PDGFRalpha) is associated with PVR in humans and strongly promotes experimental PVR driven by multiple vitreal growth factors outside the PDGF family. We sought to identify vitreal factors required for experimental PVR and to establish a potential approach to prevent PVR. Vitreous was obtained from normal rabbits or those in which PVR was either developing or stabilized. Normal vitreous contained substantial levels of growth factors and cytokines, which changed quantitatively and/or qualitatively as PVR progressed and stabilized. Neutralizing a subset of these agents in rabbit vitreous eliminated their ability to induce PVR-relevant signaling and cellular responses. A single intravitreal injection of neutralizing reagents for this subset prevented experimental PVR. To identify growth factors and cytokines likely driving PVR in humans, we subjected vitreous from patients with or without PVR to a similar series of analyses. This analysis accurately identified those agents required for vitreous-induced contraction of cells from a patient PVR membrane. We conclude that combination therapy encompassing a subset of vitreal growth factors and cytokines is a potential approach to prevent PVR. PMID- 22035644 TI - [New knowledge in genetics and inflammatory bowel disease. Are there any practical applications?]. PMID- 22035643 TI - Trajectory classes of depression in a randomized depression trial of heart failure patients: a reanalysis of the SADHART-CHF trial. AB - OBJECTIVE: The objective of this article was to determine whether, in drug intervention trials, growth mixture modeling (GMM) is able to identify drug responsive trajectory classes that are not evident in traditional growth modeling approaches. METHODS: We reanalyzed acute phase (biweekly data up to 7 occasions) and longitudinal (12 months) data on the 469 patients in the SADHART-CHF study of the safety and efficacy of sertraline for depression in patients with heart failure. GMM was used to identify the trajectory classes present in the treatment and placebo groups, based on Hamilton Depression Rating Scale scores. RESULTS: Two distinct trajectory classes were identified in the treatment group: (1) chronic depressives (12%), who remained depressed through the treatment phase; and (2) responders (88%), who had scores indicating nondepression at the conclusion of the acute phase. At baseline, chronic depressives were distinguished by higher Hamilton Depression Rating Scale scores, the presence of implantable cardioverter defibrillators, and a history of anxiety. During follow up, they were more likely to have unstable angina. Only responders remitted (70%). Three distinct trajectories were identified in the placebo group: (1) moderating depressives (19%), (2) temporary improvers (13%), and (3) responders (68%). At baseline, the classes differed in mean Hamilton Depression Rating Scale scores, responders' scores falling between the other 2 classes, and the proportion with renal disease. Only remission differed at follow-up: responders (76%), moderating depressives (21%), and temporary improvers (3%). Where the traditional analytic approach found improvement from moderate to mild depression but no significant treatment effect, GMM found response in 20% more people in the treatment group than in the placebo group. CONCLUSIONS: Unlike conventionally used, standard analytic approaches, which focus on intervention impact at study end or change from baseline to study end, GMM enables maximum use of repeated data to identify unique trajectories of latent classes that are responsive to the intervention. PMID- 22035645 TI - Peripheral primitive neuroectodermal tumour of the liver: a case report and review of the literature. AB - Peripheral primitive neuroectodermal tumour (PNET) is a malignant mesenchymal tumour. Although PNETs can occur in numerous solid organs, it is an extremely rare tumour entity, specially involving the liver. We report a 19-year-old boy with Hepatitis B Virus (HBV) infection who was diagnosed with a primary PNET of the liver. PMID- 22035646 TI - Estimating postoperative skull defect volume from CT images using the ABC method. AB - OBJECTIVES: Surgeons often perform decompressive craniectomy to alleviate a medically-refractory increase of intracranial pressure. The frequency of this type of surgery is on the rise. The goal of this study is to develop a simple formula for clinicians to estimate the volume of the skull defect, based on postoperative computed tomography (CT) studies. METHODS: We collected thirty sets of postoperative CT images from patients undergoing craniectomy. We measured the skull defect volume by computer-assisted volumetric analysis (V(m)) and our own ABC technique (V(abc)). We then compared the volumes measured by these two methods. RESULTS: The V(m) ranged from 3.2 to 76.4 mL, with a mean of 38.9 mL. The V(abc) ranged from 3.8 to 71.5 mL, with a mean of 38.5 mL. The absolute differences between V(abc) and V(m) ranged from 0.05 to 17.5 mL (mean: 3.8+/ 4.2). There was no statistically significant difference between V(abc) and V(m) (p=0.961). The correlation coefficient between V(abc) and V(m) was 0.969. In linear regression analysis, the slope was 1.00086 and the intercept was -0.0035 mL (r(2)=0.939). The residual was 5.7 mL. CONCLUSION: We confirmed that the ABC technique is a simple and accurate method for estimating skull defect volume, and we recommend routine application of this formula for all decompressive craniectomies. PMID- 22035647 TI - The impact of preoperative counseling on postoperative treatment adherence in bariatric surgery patients: a randomized controlled trial. AB - OBJECTIVE: To assess if attendance to a preoperative counseling program improved weight loss or adherence to treatment guidelines in patients who underwent bariatric surgery. METHODS: One-hundred-forty-one patients were included in the study. Sixty-nine percent chose to participate in the counseling groups. They were randomized to a Treatment group and a Control group. Thirty-one percent chose not to participate in the counseling. However, they gave their consent to assessment before and after surgery (Reference group). RESULTS: One year after bariatric surgery, 88% had a weight loss of >= 50% EWL, 37% reported more than 30 min of physical activity daily, 74% had 5-7 meals daily, and 87% took recommended vitamins. There were no differences in weight loss, eating habits, or physical exercise between the Treatment group, the Control group and the Reference group one year after surgery. CONCLUSION: Preoperative group counseling did not increase treatment adherence to recommended life-style changes. PRACTICE IMPLICATIONS: In accordance with findings in the present study, it is not reasonable to offer a preoperative counseling program for all patients undergoing bariatric surgery. Further research should focus on developing and evaluating programs for postsurgical follow-up, and identifying patients that are in need for more comprehensive treatment programs. PMID- 22035648 TI - A prospective open-label trial of quetiapine monotherapy in preschool and school age children with bipolar spectrum disorder. AB - BACKGROUND: Although bipolar disorder frequently onsets in the preschool years, treatment studies to guide management of these highly dysfunctional children are limited. This study evaluates the response to quetiapine monotherapy in preschool and school age children with bipolar spectrum disorder (BSD). METHOD: Two eight week, prospective, open-label trials utilizing identical methodology to assess the effectiveness and tolerability of quetiapine monotherapy in the treatment of BSD in preschool (age 4-6 years) and school age children (age 6-15 years). RESULTS: Forty-nine children (30 preschool and 19 school age) with BSD (Young Mania Rating Scale [YMRS] at entry: 34.5+/-5.5 and 30+/-6.5 respectively) were enrolled and 34 (20 preschool and 14 school age) completed the trial. Quetiapine was titrated to a mean endpoint dose of 175.8+/-63.8 mg/day in preschool and 248.7+/-153.1 mg/day in school age children. At endpoint, treatment with quetiapine was associated with similar and statistically significant improvement in mean YMRS scores in preschool (-14.5+/-11.5, p<0.001) and school age (-13+/ 9.8, p<0.001) children. Quetiapine was generally well tolerated with treatment limiting adverse-events observed in 3/30 preschool and 1/19 school age children. Quetiapine monotherapy in preschool and school age children was associated with significant weight gain (+3.1+/-1.8 and +7.4+/-7.7 lb respectively, p<0.001) and with clinically insignificant changes in vital signs. LIMITATIONS: As an uncontrolled study, the assessments were not blind to treatment and the effects of treatment cannot be separated from time. CONCLUSIONS: Open-label quetiapine treatment was beneficial for the treatment of BSD in preschool and school age children. Further controlled trials are warranted. PMID- 22035649 TI - The coin toss of B cells in rejection and tolerance: danger versus defense. AB - Transplantation is the preferred therapy for the end stage organ disease. Since the introduction of organ transplantation into medical practice in 1953 [1], significant progress has been achieved in patient and graft survival rates due to improvements in surgical techniques and more targeted immunosuppressive medications [2]. Nevertheless, current gaps in the management of the transplant patient stem from an incomplete understanding about the heterogeneity of the injury response in organ transplantation, at different rates and different time points after transplantation, as well as our inability to monitor the immunologic threshold of risk versus safety in each individual patient. Recent advances in immunology/transplantation biology with the advent of high throughput "omic" assays such as gene microarrays, proteomics, metabolomics, antibiomics, chemical genomics and functional imaging with nanoparticles, offers us unique methods to interrogate and decipher the variability and unpredictability of the immune response in organ transplantation (Fig. 1) [3]. Recent studies using these applications [3-8] have uncovered a critical and pivotal role for specific B cell lineages in organ injury [9] and organ acceptance [10,11] (Fig. 2). The availability of specific therapies against some of these defined B cell populations provides for an exciting new field of B cell targeted manipulation that can both abrogate the allospecific injury response, as well as promote allospecific graft accommodation and health. PMID- 22035650 TI - When the game demons take real lives: a call for global awareness raising for venous thromboembolism. PMID- 22035651 TI - Release of endothelial microparticles in vivo during atorvastatin treatment; a randomized double-blind placebo-controlled study. PMID- 22035652 TI - Prevalence and impact of complications on outcomes in patients hospitalized for oral and oropharyngeal cancer treatment. AB - OBJECTIVE: We studied the association between presence of complications and hospitalization outcomes, including hospital charges, length of stay in hospital, and in-hospital mortality. METHODS: The Nationwide Inpatient Sample for 2008 was used. All hospital discharges with a primary diagnosis of oral and oropharyngeal cancers were selected. Presence of complications was determined by using ICD-9-CM codes. The association between the presence of complications and outcomes (hospital charges, length of stay, and in-hospital mortality) was examined by multivariable linear and multivariable logistic regression analyses. The effects of several patient- and hospital-related confounders were adjusted in the regression analyses. RESULTS: A total of 17,632 hospitalizations were attributed to oral and oropharyngeal cancers. A total of 519 (2.9%) patients died in the hospitals. The total hospitalization charges were close to $1.08 billion. Oral and oropharyngeal cancers accounted for 117,472 hospitalization days (mean length of stay 6.6 days). The overall complication rate was 14.95%. The most frequently present complication was hemorrhagic complications. Among the different complications, septicemia was associated with the worst outcomes. Patients with septicemia were associated with the highest odds for in-hospital mortality (OR = 13.06, 95% CI = 3.81-48.50, P = .0001). CONCLUSIONS: Presence of complications was associated with poor outcomes, such as high in-hospital mortality rates, excess hospitalization charges, and longer length of stay in hospital. Among the different complications, septicemia was associated with the worst outcomes. PMID- 22035654 TI - Rapidly enlarging nodular lesion of the anterior maxilla. PMID- 22035653 TI - Human beta-defensin-3 (hBD-3) upregulated by LPS via epidermal growth factor receptor (EGFR) signaling pathways to enhance lymphatic invasion of oral squamous cell carcinoma. AB - OBJECTIVE: In this study, the hypothesis that hBD-3 is upregulated by LPS via epidermal growth factor receptor (EGFR) signaling pathways to enhance metastasis in oral squamous cell carcinoma (OSCC) was tested. STUDY DESIGN: hBD-3 expression in human tissue specimens was evaluated by RT-qPCR and immunohistochemical staining. The presence of hBD-3 peptide in the culture supernatants of each type of treated cells was evaluated by enzyme-linked immunosorbent assay. The chemotaxis response to LPS or hBD-3 protein of SCC-25 cells or siRNA-hBD-3 transfected cells were also measured by chemotaxis assay. Paired, 2-tailed Student t test and analysis of variance was used to assess the statistical significance between 2 groups or many groups. RESULTS: hBD-3 is highly expressed and associated with lymphatic invasion of OSCC. hBD-3 expression and EGFR phosphorylation were markedly upregulated when SCC-25 cells were treated with LPS. When SCC-25 cells were preincubated with EGFR inhibitor or TLR4-neutralizing Ab before LPS stimulation, a decrease in the expression of hBD-3 was observed. hBD-3 markedly enhanced cancer metastasis, and the chemotaxis response to LPS of SCC-25 cells was partly blocked by siRNA target hBD-3. CONCLUSION: These findings indicate that hBD-3 is upregulated by LPS via EGFR signaling pathways to enhance lymphatic invasion of OSCC. PMID- 22035655 TI - Does air pollution increase the effect of aeroallergens on hospitalization for asthma? AB - BACKGROUND: Clinical experiments demonstrate that the asthmatic response to an aeroallergen can be enhanced by prior exposure to an air pollutant. OBJECTIVE: We sought to compare the effects of ambient aeroallergens on hospitalization for asthma between high and low air pollution days in 11 large Canadian cities. METHODS: Daily time-series analysis was used, and results were adjusted for day of the week, temperature, barometric pressure, and relative humidity. RESULTS: The relative risk of admission for an interquartile increase in tree pollen levels was 1.124 (95% CI, 1.101-1.147) on days of lower values of fine particulate matter with a median aerodynamic diameter less than or equal to 2.5 MUm (PM(2.5)) compared with 1.179 (95% CI, 1.149-1.21) on days of higher PM(2.5) values. Significant (P <= .05) differences in the relative risks of admission between lower versus higher values of particulate matter with a median aerodynamic diameter less than or equal to 10 MUm in diameter were 1.149 (95% CI, 1.118-1.181) versus 1.210 (95% CI, 1.161-1.261) for ascomycetes, 1.112 (95% CI, 1.085-1.14) versus 1.302 (95% CI, 1.242-1.364) for basidiomycetes, 1.159 (95% CI, 1.125-1.195) versus 1.149 (95% CI, 1.129-1.169) for deuteromycetes, and 1.061 (95% CI, 1.016-1.107) versus 1.117 (95% CI, 1.092-1.143) for weeds. CONCLUSION: We identified an association between aeroallergens and hospitalizations for asthma, which was enhanced on days of higher air pollution. Minimizing exposure to air pollution might reduce allergic exacerbations of asthma. PMID- 22035656 TI - Oral food challenge practices among allergists in the United States. PMID- 22035657 TI - Medical and economic impact of misdiagnosis of drug hypersensitivity in hospitalized patients. PMID- 22035658 TI - Population diversity of Staphylococcus aureus isolated from bovine mastitis in Brazilian dairy herds. AB - Population diversity was evaluated in strains of Staphylococcus aureus isolated from bovine mastitis in Brazilian dairy herds by PCR-RFLP and sequencing of the 3'-terminal portion of the coagulase gene, and the susceptibility of strains to antimicrobials. The results showed great diversity in S. aureus population studied and the existence of predominant clones that account for most infections. No associations between the predominant types observed in the PCR-RFLP and the forms of presentation of the mastitis or to any of the different patterns of antimicrobial resistance were observed. PMID- 22035659 TI - Identification of NO induced and capacitation associated tyrosine phosphoproteins in buffalo (Bubalus bubalis) spermatozoa. AB - To acquire the fertilizing competence, spermatozoa must undergo a cascade of physiological and biochemical changes collectively defined as capacitation. Compelling evidence signifies that the global increase in protein tyrosine phosphorylation is the driving factor for capacitation. In our laboratory, we previously demonstrated that nitric oxide (NO) induces capacitation in buffalo sperm and is associated with an increase in protein tyrosine phosphorylation. The aim of the present study is to identify the proteins undergo tyrosine phosphorylation during NO induced buffalo sperm capacitation using 2-D immunoblotting and mass spectrometry. The percentage of progressively motile and capacitated sperm was more in presence of l-arginine. Along with known tyrosine phosphoproteins like ATP synthase subunit beta, pyruvate dehydrogenase E1 component subunit beta, GST mu 3, F-actin capping protein subunit beta 2, GPD2 and VDAC2, interestingly novel tyrosine phosphoprotein substrates such as actin, serine/threonine-protein phosphatase PP1-gamma catalytic subunit, and glutamine synthetase were also identified which might be specific to the NO induced signaling and also emphasizes the species specificity with respect to tyrosine phosphorylation of proteins during capacitation. In conclusion, this study forms an essential step in delineating the proteins undergo tyrosine phosphorylation in response to NO induced signaling pathways during capacitation of buffalo sperm. PMID- 22035661 TI - Feasibility and acute toxicity of hypofractionated radiation in large-breasted patients. AB - PURPOSE: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. METHODS AND MATERIALS: A review was conducted of all patients consecutively treated with HypoRT at the University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a "field-in-field" technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetric parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. RESULTS: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m(2). Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). CONCLUSIONS: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women with a PTV volume >2,500 mL. PMID- 22035660 TI - The rhomboid protease family: a decade of progress on function and mechanism. AB - Rhomboid proteases are the largest family of enzymes that hydrolyze peptide bonds within the cell membrane. Although discovered to be serine proteases only a decade ago, rhomboid proteases are already considered to be the best understood intramembrane proteases. The presence of rhomboid proteins in all domains of life emphasizes their importance but makes their evolutionary history difficult to chart with confidence. Phylogenetics nevertheless offers three guiding principles for interpreting rhomboid function. The near ubiquity of rhomboid proteases across evolution suggests broad, organizational roles that are not directly essential for cell survival. Functions have been deciphered in only about a dozen organisms and fall into four general categories: initiating cell signaling in animals, facilitating bacterial quorum sensing, regulating mitochondrial homeostasis, and dismantling adhesion complexes of parasitic protozoa. Although in no organism has the full complement of rhomboid function yet been elucidated, links to devastating human disease are emerging rapidly, including to Parkinson's disease, type II diabetes, cancer, and bacterial and malaria infection. Rhomboid proteases are unlike most proteolytic enzymes, because they are membrane immersed; understanding how the membrane immersion affects their function remains a key challenge. PMID- 22035662 TI - Adjuvant radiotherapy for palpable melanoma metastases to the groin: when to irradiate? AB - PURPOSE: To determine the efficacy of and criteria for postoperative radiotherapy (PORT) in patients with palpable melanoma metastases to the groin. METHODS AND MATERIALS: Patients with palpable metastases to the groin who were treated with therapeutic nodal dissection during 2000 to 2006 were identified in a prospective institutional database. RESULTS: In 101 patients, 103 therapeutic nodal dissections were performed; 37 of these were treated with PORT to a median equivalent dose (eqTD(2)) of 50.6 Gy (range, 50-72 Gy). In the surgery-only and PORT groups, 2-year regional control rates were 86% (95% confidence interval [CI] 76-95%) and 91% (95% CI, 81-100%), respectively (p = 0.395). Of five recurrences in radiation-treated patients, four were of dermal type, and in three of these cases, no bolus over the operative scar was used. PORT improved 2-year regional control (46% [95% CI, 11-82%] vs. 82% [95% CI, 63-100%], p = 0.022) among patients in which the sum of risk factors present (i.e., risk factor score) was >=2. In multivariate analysis, risk-factor score (<2 vs. >=2: HR, 2.93; 95% CI, 1.00-8.56; p < 0.0001) and PORT (yes vs. no: HR, 7.81; 95% CI, 2.83-21.74; p = 0.050) was predictive for regional control and on logistic-regression testing, number of involved lymph nodes was predictive for systemic dissemination (p = 0.011). CONCLUSIONS: PORT should follow therapeutic nodal dissection in cases with two or more adverse factors. More conventional fractionation (<=2.5 Gy), cumulative eqTD(2) <60 Gy and use of bolus over the operative scar are recommended. PMID- 22035663 TI - Target volume delineation in oropharyngeal cancer: impact of PET, MRI, and physical examination. AB - INTRODUCTION: Sole utilization of computed tomography (CT) scans in gross tumor volume (GTV) delineation for head-and-neck cancers is subject to inaccuracies. This study aims to evaluate contributions of magnetic resonance imaging (MRI), positron emission tomography (PET), and physical examination (PE) to GTV delineation in oropharyngeal cancer (OPC). METHODS: Forty-one patients with OPC were studied. All underwent contrast-enhanced CT simulation scans (CECTs) that were registered with pretreatment PETs and MRIs. For each patient, three sets of primary and nodal GTV were contoured. First, reference GTVs (GTVref) were contoured by the treating radiation oncologist (RO) using CT, MRI, PET, and PE findings. Additional GTVs were created using fused CT/PET scans (GTVctpet) and CT/MRI scans (GTVctmr) by two other ROs blinded to GTVref. To compare GTVs, concordance indices (CI) were calculated by dividing the respective overlap volumes by overall volumes. To evaluate the contribution of PE, composite GTVs derived from CT, MRI, and PET (GTVctpetmr) were compared with GTVref. RESULTS: For primary tumors, GTVref was significantly larger than GTVctpet and GTVctmr (p < 0.001). Although no significant difference in size was noted between GTVctpet and GTVctmr (p = 0.39), there was poor concordance between them (CI = 0.62). In addition, although CI (ctpetmr vs. ref) was low, it was significantly higher than CI (ctpet vs. ref) and CI (ctmr vs. ref) (p < 0.001), suggesting that neither modality should be used alone. Qualitative analyses to explain the low CI (ctpetmr vs. ref) revealed underestimation of mucosal disease when GTV was contoured without knowledge of PE findings. Similar trends were observed for nodal GTVs. However, CI (ctpet vs. ref), CI (ctmr vs. ref), and CI (ctpetmr vs. ref) were high (>0.75), indicating that although the modalities were complementary, the added benefit was small in the context of CECTs. In addition, PE did not aid greatly in nodal GTV delineation. CONCLUSION: PET and MRI are complementary and combined use is ideal. However, the low CI (ctpetmr vs. ref) particularly for primary tumors underscores the limitations of defining GTVs using imaging alone. PE is invaluable and must be incorporated. PMID- 22035664 TI - Breast ultrasound: an indispensable tool. PMID- 22035665 TI - Case of the season: Large B-cell lymphoma involving both breasts. PMID- 22035666 TI - The breast ultrasound lexicon: breast imaging reporting and data system (BI RADS). PMID- 22035667 TI - Mammographic-sonographic correlation. PMID- 22035668 TI - Utility of second-look ultrasound in the evaluation of MRI-detected breast lesions. PMID- 22035669 TI - Sonographic features of inflammatory breast cancer. PMID- 22035670 TI - Intraoperative breast ultrasound. PMID- 22035671 TI - Screening for breast cancer with sonography. PMID- 22035672 TI - New sonographic breast technologies. PMID- 22035673 TI - Automated 3-D breast ultrasound as a promising adjunctive screening tool for examining dense breast tissue. PMID- 22035674 TI - Measurement of intraarticular wrist joint biomechanics with a force controlled system. AB - Pathologies of the wrist, such as fractures or instabilities, can lead to alterations in joint biomechanics. Accurate treatment of these pathologies is a frequent challenge for the surgeon. For biomechanical investigations, a test setup that applies physiological loading of the wrist joint is necessary. A force controlled test-bench with agonistic and antagonistic muscle forces was built to move six fresh frozen human upper extremities through flexion and extension of the wrist joint. Tendon forces, range of motion, intraarticular contact area and contact pressure of the lunate and scaphoid facet as well as tendon excursion were investigated and compared with the current literature. During wrist motion the extensors exerted double the force of the flexors. Capsulotomy and sensor insertion decreased the range of motion from 63.4 degrees (SD 14.1) to 45.9 degrees (SD 23.7). The ratio of force transmitted through the radius and ulna was 77:23 and pressure distribution between the scaphoid and lunate facet showed a 70:30 relationship. The obtained data indicate a good agreement with the available literature. Therefore, the force controlled test-bench in combination with intraarticular radiocarpal measurements can be used to investigate the influence of wrist pathologies on joint biomechanics. PMID- 22035676 TI - Concussion and mild traumatic brain injury: current and future concepts. Introduction. PMID- 22035675 TI - Relationship between resting blood pressure and laboratory-induced pain among healthy children. AB - BACKGROUND: Adult studies have demonstrated that increased resting blood pressure (BP) levels correlate with decreased pain sensitivity. However, few studies have examined the relationship between BP and experimental pain sensitivity among children. OBJECTIVES: This study investigated the association between resting BP levels and experimental pain tolerance, intensity, and unpleasantness in healthy children. We also explored whether these BP-pain relationships were age and gender dependent. METHODS: Participants underwent separate 4-trial blocks of cutaneous pressure and thermal pain stimuli, and 1 trial of a cold pain stimulus in counterbalanced order. RESULTS: A total of 235 healthy children (49.6% female; mean age 12.7 [2.9] years; age range 8-18 years) participated. The study revealed specific gender-based BP-pain relationships. Girls with higher resting systolic BP levels were found to have lower thermal intensity ratings than girls with lower resting systolic BP levels; this relationship was stronger among adolescent girls than among younger girls. Among young girls (8-11 years), those with higher resting diastolic BP (DBP) levels were found to have lower cold intensity and unpleasantness as well as lower thermal intensity ratings than did young girls with lower resting DBP levels; these DBP-pain response relationships were not seen among adolescent girls. CONCLUSIONS: Age, rather than resting BP, was predictive of laboratory pain ratings in boys. The findings suggest that the relationship between BP and experimental pain is age and gender dependent. These aspects of cardiovascular relationships to pain in males and females need further attention to understand their clinical importance. PMID- 22035677 TI - Epidemiology of concussion and mild traumatic brain injury. AB - Mild traumatic brain injury (mTBI) is a common public health concern that affects millions of people each year. The available epidemiology of mTBI may contain insights that can guide future identification, prevention, and treatment efforts. This article discusses epidemiology of both non-sports-related mTBI and sports related concussion. Specific occupational factors, emergency department data, and meta-analysis regarding mTBI are reviewed and discussed. With regard to sports concussion, the article will discuss data related to the sport played, the individual's position, level of play, and gender differences. Although males make up a larger percentage of cases than do females throughout the majority of reviewed non-sports-related mTBI data, the sports literature indicates that rates are higher in women when similar sports are compared. Identifiable risk factors within sports include female gender, sport, and position played. Emerging trends across mTBI include increased incidence and decreased rate of hospitalization for mTBI. PMID- 22035678 TI - The pathophysiology of concussion. AB - Concussion is defined as a biomechanically induced brain injury characterized by the absence of gross anatomic lesions. Early and late clinical symptoms, including impairments of memory and attention, headache, and alteration of mental status, are the result of neuronal dysfunction mostly caused by functional rather than structural abnormalities. The mechanical insult initiates a complex cascade of metabolic events leading to perturbation of delicate neuronal homeostatic balances. Starting from neurotoxicity, energetic metabolism disturbance caused by the initial mitochondrial dysfunction seems to be the main biochemical explanation for most postconcussive signs and symptoms. Furthermore, concussed cells enter a peculiar state of vulnerability, and if a second concussion is sustained while they are in this state, they may be irreversibly damaged by the occurrence of swelling. This condition of concussion-induced brain vulnerability is the basic pathophysiology of the second impact syndrome. N-acetylaspartate, a brain-specific compound representative of neuronal metabolic wellness, is proving a valid surrogate marker of the post-traumatic biochemical damage, and its utility in monitoring the recovery of the aforementioned "functional" disturbance as a concussion marker is emerging, because it is easily detectable through proton magnetic resonance spectroscopy. PMID- 22035679 TI - Concussion in the pediatric and adolescent population: "different population, different concerns". AB - Sports-related concussions are common among pediatric and adolescent athletes, yet a scarcity of age-specific research often has meant that practitioners use guidelines developed for collegiate or adult populations. This situation is changing, as more studies are being published about this population that bears special attention because of the immaturity of the developing brain. This article describes existing knowledge about the epidemiology and etiology of concussions in youth athletes; discusses issues related to assessment, clinical management, and return to activity; examines special concerns related to the effects of concussion on the developing brain; and discusses prevention and education initiatives related to concussion in youth athletes. PMID- 22035680 TI - Concussions and the military: issues specific to service members. AB - Since October 2001, more than 1.6 million American military service members have deployed to Iraq and Afghanistan in the Global War on Terrorism. It is estimated that between 5% and 35% of them have sustained a concussion, also called mild traumatic brain injury (mTBI), during their deployment. Up to 80% of the concussions experienced in theater are secondary to blast exposures. The unique circumstances and consequences of sustaining a concussion in combat demands a unique understanding and treatment plan. The current literature was reviewed and revealed a paucity of pathophysiological explanations on the nature of the injury and informed treatment plans. However, through observation and experience, a theoretical but scientifically plausible model for why and how blast injuries experienced in combat give rise to the symptoms that affect day-to-day function of service members who have been concussed has been developed. We also are able to offer treatment strategies based on our evaluation of the current literature and experience to help palliate postconcussive symptoms. The purpose of this review is to elucidate common physical, cognitive, emotional, and situational challenges, and possible solutions for this special population of patients who will be transitioning into the civilian sector and interfacing with health professionals. There is a need for further investigation and testing of these strategies. PMID- 22035681 TI - Mild traumatic brain injury in the occupational setting. AB - The evaluation and management of mild traumatic brain injury (mTBI) in the occupational setting may pose significant challenges for even the most-seasoned practitioner. Providers must simultaneously address the clinical management of mTBI and be familiar with the systematic and administrative requirements related to the management of injured workers with mTBI who are covered by workers' compensation insurance, including causation, return to work, and the potential of permanent impairment. Given the primarily subjective nature of many mTBI symptoms, an injured worker with a delayed recovery may raise the question, if not suspicion, of symptom magnification and secondary gain. This review discusses the evaluation and treatment of the injured worker with mTBI, and focuses on the medicolegal issues that are present in the workers' compensation system, especially the role of neuropsychological evaluations. Although significant differences exist regarding classification schema, for the purposes of this discussion, mTBI is used to encompass the terms concussion, postconcussive syndrome, and persistent postconcussive syndrome. PMID- 22035682 TI - Postconcussion syndrome: a physiatrist's approach. PMID- 22035683 TI - Headache management in concussion and mild traumatic brain injury. AB - Headache is one of the most common symptoms after traumatic brain injury (TBI), and posttraumatic headache (PTH) may be part of a constellation of symptoms that is seen in the postconcussive syndrome. PTH has no defining clinical features; currently it is classified as a secondary headache based on its close temporal relationship to the injury. A growing number of studies are characterizing PTH by using primary headache classifications. Moderate to severe PTH that is often disabling may be classified as migraine or probable migraine and is found in substantial numbers of individuals. Recent data from civilian adult, pediatric, and military populations all find that PTH may be more of a chronic problem than previously thought, with a prevalence of close to half of the injured population. In addition, if PTH definitions are strictly adhered to, then many cases of PTH may be missed, thus underestimating the scope of the problem. New headaches may be reported well after the 7 days required for diagnosis of PTH by the guidelines of the International Classification of Headache Disorders, 2nd edition. A history of headache before a head injury occurs and female gender are possible risk factors for headache after TBI. Treatment of PTH may be acute or preventive, and recommendations are made for the use of migraine-specific acute therapy when indicated. Preventive therapy may be considered when PTH is frequent, disabling, or refractory to acute therapies. Comorbid conditions should be considered when choosing an appropriate preventive therapy. The symptom of headache as a "return to play" or "return to duty" barrier must be viewed in the context of other symptoms of mild TBI. PMID- 22035684 TI - Imaging modalities in mild traumatic brain injury and sports concussion. AB - Mild traumatic brain injury is a significant public health issue that has been gaining considerable attention over the past few years. After injury, a large percentage of patients experience postconcussive symptoms that affect work and school performance and that carry significant medicolegal implications. Conventional imaging modalities (computed tomography and magnetic resonance imaging) are insensitive to microstructural changes and underestimate the degree of diffuse axonal injury and metabolic changes. Newer imaging techniques have attempted to better diagnose and characterize diffuse axonal injury and the metabolic and functional aspects of traumatic brain injury. The following review article summarizes the currently available imaging studies and describes the novel and more investigational techniques available for mild traumatic brain injury. A suggested algorithm is offered. PMID- 22035685 TI - Neuropsychological testing as it relates to recovery from sports-related concussion. AB - Concussion is a challenging injury for the sports medicine team, and neuropsychological testing has been used as an adjunct to other clinical measures for assessment and management, and to guide return-to-play decisions. Understanding the limitations as well as the role of neuropsychological testing in the evaluation and management of sports-related concussion is important for the sports medicine team. This article will review the evidence regarding the utility of neuropsychological testing as it relates to concussion in sports. PMID- 22035686 TI - Neuropsychological testing point/counterpoint. PMID- 22035687 TI - Considerations for return-to-play and retirement decisions after concussion. AB - Return-to-play and retirement decisions after concussion are often difficult and complex. The complexity of these decisions may be influenced by many factors, including the number, proximity, and severity of previous concussions; gender; age; sport played; exposure to head impacts; and predisposing or pre-existing conditions. These circumstances and conditions can confound the decisions concerning return to play and retirement. Clinicians should carefully weigh how these circumstances and conditions influence quality of life and how they interact with the effects of concussion. Furthermore, clinicians should consider past and potential exposures to both subconcussive and concussive impacts during the athlete's lifetime when deliberating a return to play or retirement. The purpose of this overview is to highlight and discuss these issues as they factor into the return-to-play and retirement decisions after a concussive injury in an effort to provide clinicians with evidence-based information that can be used in the decision-making process. PMID- 22035688 TI - Postconcussive impairment differences across a multifaceted concussion assessment protocol. AB - OBJECTIVE: To examine the proportion of athletes with concussion and with impairment disagreements across various clinical concussion assessment measures. DESIGN: Quasi-experimental repeated measures design. SETTING: Clinical research laboratory. PARTICIPANTS: A sample of 100 collegiate-aged athletes participated in the study (mean [SD] age, 18.5 +/- 1.1 years; mean [SD] height, 180.6 +/- 9.9 cm; mean [SD] weight, 84.1 +/- 20.6 kg). METHODS OR INTERVENTIONS: Participants completed preseason baseline and postconcussive injury assessments on a clinical assessment battery, including a 17-item graded symptom checklist, a computerized neurocognitive assessment, and a balance performance assessment. MAIN OUTCOME MEASUREMENTS: Symptom severity total score, 8 cognitive domain scores from the Automated Neuropsychological Assessment Metrics, and the composite balance score obtained from the Sensory Organization Test served as outcome measures for the study. McNemar tests of paired proportions were then used to analyze impairment disagreements (where one measure identified impairments not identified by the other) between the study outcome measures. The alpha level was set to .05 a priori. RESULTS: We observed significant disagreements between symptom severity total scores, and all other measures used in the study in which symptom severity total scores identified more impairments than all other measures. In addition, we observed significant disagreements for half of the clinical measures used in the study, with disagreement proportions that ranged from 22%-52%. CONCLUSIONS: Our study underscores the importance of using a multifaceted approach for management of concussion that includes assessment of symptom severity, cognitive function, and balance. Use of this multifaceted approach also can aid clinicians in understanding other comorbidities that may complicate the management of concussion. PMID- 22035689 TI - Biomarkers, genetics, and risk factors for concussion. AB - It is estimated that between 1.6 and 3.8 million concussions occur annually in the United States. Although frequently regarded as benign, concussions can lead to multiple different adverse outcomes, including prolonged postconcussive symptoms, chronic traumatic encephalopathy, cognitive impairment, early onset dementia, movement disorders, psychiatric disorders, motor neuron disease, and even death. Therefore it is important to identify individuals with concussion to provide appropriate medical care and minimize adverse outcomes. Furthermore, it is important to identify individuals who are predisposed to sustaining a concussion or to having an adverse outcome after concussion. This article will discuss the current research on serum biomarkers for concussion, genetic influence on concussion, risk factors associated with concussion predisposition and poor outcome, and practical suggestions for the application of this information in clinical practice. PMID- 22035690 TI - Long-term consequences of repetitive brain trauma: chronic traumatic encephalopathy. AB - Chronic traumatic encephalopathy (CTE) has been linked to participation in contact sports such as boxing and American football. CTE results in a progressive decline of memory and cognition, as well as depression, suicidal behavior, poor impulse control, aggressiveness, parkinsonism, and, eventually, dementia. In some individuals, it is associated with motor neuron disease, referred to as chronic traumatic encephalomyelopathy, which appears clinically similar to amyotrophic lateral sclerosis. Results of neuropathologic research has shown that CTE may be more common in former contact sports athletes than previously believed. It is believed that repetitive brain trauma, with or possibly without symptomatic concussion, is responsible for neurodegenerative changes highlighted by accumulations of hyperphosphorylated tau and TDP-43 proteins. Given the millions of youth, high school, collegiate, and professional athletes participating in contact sports that involve repetitive brain trauma, as well as military personnel exposed to repeated brain trauma from blast and other injuries in the military, CTE represents an important public health issue. Focused and intensive study of the risk factors and in vivo diagnosis of CTE will potentially allow for methods to prevent and treat these diseases. Research also will provide policy makers with the scientific knowledge to make appropriate guidelines regarding the prevention and treatment of brain trauma in all levels of athletic involvement as well as the military theater. PMID- 22035691 TI - Changing the culture of concussion: education meets legislation. PMID- 22035692 TI - Hazardous dichloromethane recovery in combined temperature and vacuum pressure swing adsorption process. AB - Organic vapors emitted from solvents used in chemical and pharmaceutical processes, or from hydrocarbon fuel storage stations at oil terminals, can be efficiently captured by adsorption onto activated carbon beds. To recover vapors after the adsorption step, two modes of regeneration were selected and could be possibly combined: thermal desorption by hot nitrogen flow and vacuum depressurization (VTSA). Because of ignition risks, the conditions in which the beds operate during the adsorption and regeneration steps need to be strictly controlled, as well as optimized to maintain good performances. In this work, the optimal conditions to be applied during the desorption step were determined from factorial experimental design (FED), and validated from the process simulation results. The regeneration performances were compared in terms of bed regeneration rate, concentration of recovered volatile organic compounds (VOC) and operating costs. As an example, this methodology was applied in case of dichloromethane. It has been shown that the combination of thermal and vacuum regeneration allows reaching 82% recovery of dichloromethane. Moreover, the vacuum desorption ended up in cooling the activated carbon bed from 93 degrees C to 63 degrees C and so that it significantly reduces the cooling time before starting a new cycle. PMID- 22035693 TI - Photocatalytic degradation of metoprolol tartrate in suspensions of two TiO2 based photocatalysts with different surface area. Identification of intermediates and proposal of degradation pathways. AB - This study investigates the efficiency of the photocatalytic degradation of metoprolol tartrate (MET), a widely used beta(1)-blocker, in TiO(2) suspensions of Wackherr's "Oxyde de titane standard" and Degussa P25. The study encompasses transformation kinetics and efficiency, identification of intermediates and reaction pathways. In the investigated range of initial concentrations (0.01-0.1 mM), the photocatalytic degradation of MET in the first stage of the reaction followed approximately a pseudo-first order kinetics. The TiO(2) Wackherr induced a significantly faster MET degradation compared to TiO(2) Degussa P25 when relatively high substrate concentrations were used. By examining the effect of ethanol as a scavenger of hydroxyl radicals (OH), it was shown that the reaction with OH played the main role in the photocatalytic degradation of MET. After 240 min of irradiation the reaction intermediates were almost completely mineralized to CO(2) and H(2)O, while the nitrogen was predominantly present as NH(4)(+). Reaction intermediates were studied in detail and a number of them were identified using LC-MS/MS (ESI+), which allowed the proposal of a tentative pathway for the photocatalytic transformation of MET as a function of the TiO(2) specimen. PMID- 22035694 TI - Analysis of hazardous organic residues from sodium hydrosulfite industry and utilization as raw materials in a novel solid lubricant production. AB - The hazardous organic residual wastes produced by the sodium hydrosulfite industry are demonstrated to be convertible into a novel solid lubricant. Identification and isolation of the organic residues are achieved by Fourier transform infrared (FTIR) spectroscopy, gas chromatography-mass spectrometry (GC MS), and nuclear magnetic resonance (NMR). FTIR and GC-MS provide important information about the residues and the two main components obtained by column chromatography are further analyzed by NMR. The main organic residues are found to be thiodiglycol and 2,2'-dithiodiethanol which have potential applications in petroleum drilling because of their S-S and/or C-S functional groups. The lubricity of the organic residues is subsequently studied and the influence of different adsorbents on the lubricity is investigated and discussed. This homemade lubricant is observed to have good lubricity and by increasing the concentration of the commercial solid lubricant M, the lubricity diminishes. The process is expected to not only have commercial impact but also help to reduce environmental pollution. PMID- 22035695 TI - Development of a fritless packed column for capillary electrochromatography-mass spectrometry. AB - A novel procedure was developed for the fabrication of a fritless packed column for the coupling of capillary electrochromatography (CEC) to mass spectrometry (MS). The process involved the formation of internal tapers on two separate columns. Once the internal tapers are formed and the columns are packed, the untapered ends of each column were joined together by a commercially available connector. Several advantages of the fritless columns are described. First, the design used here eventually eliminates the need for any frits thus reducing the possibility of bubble formation seen with fritted packed columns. In addition, this is the first report in which the internal tapers are formed at both the inlet and outlet column ends making the fritless CEC-MS column more robust compared to only one report with externally tapered counterparts. Second, a comparison of internally tapered single frit packed CEC-MS (previously developed in our laboratory) column versus fritless CEC-MS column reported here shows that the latter provides better efficiency, suggesting no dead volume with equally good sensitivity and chiral resolution of (+/-)-aminoglutethimide. The fritless column procedure is universal and was used to prepare a series of columns with a variety of commercially available packing material (mixed mode strong cation exchange, SCX; mixed mode strong anion exchange, SAX; C-18) for the separation and MS detection of short chain non-chromophoric polar amines, long chain nonchromophic anionic surfactant as well as oligomers of non-chromophoric non ionic surfactants, respectively. The fritless columns showed good intra-day repeatability and inter-day reproducibility of retention times, chiral and achiral resolutions and peak areas. Very satisfactory column-to-column and operator-to-operator reproducibility was demonstrated. PMID- 22035696 TI - Direct quantification of mono- and di-D-alpha-tocopherol polyethylene glycol 1000 succinate by high performance liquid chromatography. AB - A simple and direct reversed-phase high performance liquid chromatography (RP HPLC) method with UV detection was developed and validated for the determination of mono- and di-D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS 1000) in TPGS mixture. Before the HPLC analysis, mono- and di-TPGS 1000 were separated by simulated moving bed (SMB) chromatography system and characterized by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The mass spectrometric results confirmed that the molar mass distribution of TPGS prepared in our laboratory was very close to that of the product of Eastman Chemical Company with similar n- (average polymerization degree), M(n)- (number average molecular weight) and M(w)- (weight-average molecular weight). The HPLC analysis was carried out on a C30 analytical column with mobile phases comprised of acetonitrile (A) and isopropanol (B) in gradient conditions. Validation of the analytical method was done on the following parameters: system suitability, linearity, limits of detection and quantification, accuracy and precision, method robustness and solution stability. The linearity of the calibration curves for mono- and di-TPGS 1000 from both sources was found to be good (r(2)>0.9996). The recovery values were from 94.6% to 103.3% for mono-TPGS, and 93.5% to 103.3% for di-TPGS. This method could be successfully used in the direct quantification of mono- and di-TPGS in TPGS 1000 mixture using TPGS standards with similar molecular mass distributions although derived from different sources. PMID- 22035697 TI - Plate height formula widely accepted in GC is not correct. PMID- 22035698 TI - Hydrodynamic chromatography of macromolecules using polymer monolithic columns. AB - The selectivity window of size-based separations of macromolecules was tailored by tuning the macropore size of polymer monolithic columns. Monolithic materials with pore sizes ranging between 75 nm and 1.2 MUm were prepared in situ in large I.D. columns. The dominant separation mechanism was hydrodynamic chromatography in the flow-through pores. The calibration curves for synthetic polymers matched with the elution behavior by HDC separations in packed columns with 'analyte-to pore' aspect ratios (lambda) up to 0.2. For large-macropore monoliths, a deviation in retention behavior was observed for small polystyrene polymers (M(r)<20 kDa), which may be explained by a combined HDC-SEC mechanism for lambda<0.02. The availability of monoliths with very narrow pore sizes allowed investigation of separations at high lambda values. For high-molecular weight polymers (M(r)>300,000 Da) confined in narrow channels, the separation strongly depended on flow rate. Flow-rate dependent elution behavior was evaluated by calculation of Deborah numbers and confirmed to be outside the scope of classic shear deformation or slalom chromatography. Shear-induced forces acting on the periphery of coiled polymers in solution may be responsible for flow-rate dependent elution. PMID- 22035699 TI - Fibroblast growth factor receptor 1- 5-hydroxytryptamine 1A heteroreceptor complexes and their enhancement of hippocampal plasticity. AB - BACKGROUND: The hippocampus and its 5-hydroxytryptamine transmission plays an important role in depression related to its involvement in limbic circuit plasticity. METHODS: The analysis was made with bioluminescence resonance energy transfer, co-immunoprecipitation, in situ proximity ligation assay, binding assay, in cell western and the forced swim test. RESULTS: Using bioluminescence resonance energy transfer analysis, fibroblast growth factor receptor 1 (FGFR1)-5 hydroxytryptamine 1A (5-HT1A) receptor complexes have been demonstrated and their specificity and agonist modulation characterized. Their presence based on co immunoprecipitation and proximity ligation assay has also been indicated in hippocampal cultures and rat dorsal hippocampal formation showing a neuronal location. In vitro assays on extracellular signal-regulated kinases 1 and 2 phosphorylation have shown synergistic increases in signaling on coactivation with fibroblast growth factor 2 (FGF2) and a 5-HT1A agonist, and dependent on the heteroreceptor interface. In vitro and in vivo studies also revealed a 5-HT1A agonist induced phosphorylation of FGFR1 and extracellular signal-regulated kinase 1/2 in rat hippocampus without changing FGF2 levels. Co-activation of the heteroreceptor also resulted in synergistic increases in extensions of PC12 cells and neurite densities and protrusions in primary hippocampal cultures dependent on the receptor interface. The combined acute and repeated intracerebroventricular treatment with FGF2 and 8-OH-DPAT was found to produce evidence of highly significant antidepressant actions in the forced swim test. CONCLUSIONS: The findings indicate that neurotrophic and antidepressant effects of 5-HT in brain may, in part, be mediated by activation of the 5-HT1A receptor protomer in the hippocampal FGFR1-5-HT1A receptor complex enhancing the FGFR1 signaling. PMID- 22035700 TI - Integrated treatment programs for individuals with concurrent substance use disorders and trauma experiences: a systematic review and meta-analysis. AB - The purpose of this study was to examine the evidence of psychotherapeutic integrated treatment (IT) programs for individuals with concurrent substance use disorders and trauma histories. Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, Web of knowledge, PubMed, PsycINFO, CINAHL, PILOTS, and EMBASE identified 17 IT trials (9 controlled trials). Both narrative review and meta-analysis indicate that IT effectively reduces trauma symptoms and substance abuse from pretreatment to longest follow-up. However, IT and nonintegrated programs appear to produce similar declines in symptoms. Methodological issues limiting the current body of work and recommendations for future research are discussed. Well-designed randomized controlled trials are clearly needed, particularly large sample studies evaluating understudied IT programs and exposure-based approaches. PMID- 22035701 TI - Predictive validity of the EuropASI: clinical diagnosis or composite scoring? AB - This study assessed the correlation between the areas of the interviewer severity rating (ISR) and the areas of the composite scores (CSs) of the European version of the Addiction Severity Index (EuropASI). It evaluated the predictive validity of both types of scoring with regard to completion of treatment. For this purpose, 252 patients were interviewed using the EuropASI; 38.9% of patients discontinued treatment. Results indicated a high correlation between various areas of the ISR and the CS, except the legal and family-others scales. Regarding predictive results, patients with a score greater than 3 in the ISR family area were more likely to quit the program compared with patients with a score lower than 3. Patients with a CS score that was greater than 0.34 in the alcohol use area were more likely to drop out of treatment. When both ISR and CS scores were included in the prediction model, the ISR family area was a better predictor. PMID- 22035703 TI - Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. AB - Intrauterine administration of autologous peripheral blood mononuclear cells (PBMC) activated by HCG in vitro are reported to improve implantation rates in patients with repeated failure of IVF-ET. In this study, we examined the effects of intrauterine administration of freshly isolated PBMC on clinical pregnancy and the implantation rates of patients who received frozen/thawed embryo transfer by prospective cohort study. Patients who had not achieved a successful pregnancy despite at least one or more IVF-ET sessions were enrolled in this study (n = 253, 253 cycles). Based on the patient's treatment preferences, PBMC were freshly isolated from each patient and then administered to the intrauterine cavity of that patient. Frozen/thawed embryo transfer was performed and the success of implantation in the PBMC-treated group (n = 83, 83 cycles) was compared with that in the non-treated control groups (n = 170, 170 cycles). There were no significant differences in the clinical pregnancy rate (34.9% vs. 32.9%), implantation rate (21.6% vs. 21.1%) and live birth delivery rate (21.7% vs. 21.8%) between PBMC-treated and non-treated groups. However, when the analyses were restricted to patients who had three or more implantation failures, the clinical pregnancy rate and the implantation rate in the PBMC-treated group (42.1% and 25.0%, p<0.05; n = 19 and 32, respectively) were significantly higher than those in the non-treated group (16.7% and 9.4%, p<0.05; n = 36 and 64, respectively). These findings indicate that intrauterine administration of autologous PBMC freshly isolated from patients, effectively improves embryo implantation in patients with three or more IVF failures. PMID- 22035702 TI - Hepatitis B virus and hepatitis C virus services offered by substance abuse treatment programs in the United States. AB - Although substance abuse treatment programs are important contact points for providing health services for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, availability of services in these programs has not been well characterized. This study evaluated the spectrum of HBV and HCV services offered by substance abuse treatment programs within the National Drug Abuse Treatment Clinical Trials Network. Our survey of substance abuse treatment program administrators covered availability of testing for HBV and HCV; hepatitis A virus (HAV) and HBV immunization; and HCV medical and nonmedical services. There were also questions covering clarity of guidelines for HBV and HCV testing and HAV and HBV immunization. Differences between methadone and nonmethadone programs were examined. Despite the importance of substance abuse in sustaining the hepatitis epidemics, few programs offer comprehensive HBV and HCV testing or HCV health care services. Interventions to improve access to hepatitis services for substance-abusing patients are needed. PMID- 22035704 TI - [Acute confusional syndrome in the elderly admitted to internal medicine]. PMID- 22035705 TI - [Useful and practical tests for the early detection of sarcopenia in older adults]. PMID- 22035706 TI - The two main theories on dental bruxism. AB - Bruxism is characterized by non-functional contact of mandibular and maxillary teeth resulting in clenching or grating of teeth. Theories on factors causing bruxism are a matter of controversy in current literature. The dental profession has predominantly viewed peripheral local morphological disorders, such as malocclusion, as the cause of clenching and gnashing. This etiological model is based on the theory that occlusal maladjustment results in reduced masticatory muscle tone. In the absence of occlusal equilibration, motor neuron activity of masticatory muscles is triggered by periodontal receptors. The second theory assumes that central disturbances in the area of the basal ganglia are the main cause of bruxism. An imbalance in the circuit processing of the basal ganglia is supposed to be responsible for muscle hyperactivity during nocturnal dyskinesia such as bruxism. Some authors assume that bruxism constitutes sleep-related parafunctional activity (parasomnia). A recent model, which may explain the potential imbalance of the basal ganglia, is neuroplasticity. Neural plasticity is based on the ability of synapses to change the way they work. Activation of neural plasticity can change the relationship between inhibitory and excitatory neurons. It seems obvious that bruxism is not a symptom specific to just one disease. Many forms (and causes) of bruxism may exist simultaneously, as, for example, peripheral or central forms. PMID- 22035707 TI - Ambulatory venovenous extracorporeal respiratory support as a bridge for cystic fibrosis patients to emergent lung transplantation. AB - Venovenous extracorporeal membrane oxygenation (VV ECMO) is a therapeutic option to bridge patients with advanced lung disease to lung transplantation. The use of VV ECMO avoids the use of mechanical ventilation while allowing patients to participate in physical therapy and to eat normally while receiving respiratory support. We describe the successful use of ambulatory single-venous VV ECMO as a bridge to bilateral lung transplantation in 4 patients with end-stage lung disease due to cystic fibrosis who developed acute hypercapnic respiratory failure. The use of ambulatory single-venous VV ECMO was safe and effective in this small cohort of CF patients. Based on our experiences, our belief is that a key step in the treatment course was early application of VV ECMO soon after development of acute respiratory failure requiring mechanical ventilation. PMID- 22035708 TI - Cultures of seeing embryos and cells in 3-dimensions and flatness. PMID- 22035709 TI - Life lines: An art history of biological research around 1800. AB - Around 1800, the scientific "illustrator" emerged as a new artistic profession in Europe. Artists were increasingly sought after in order to picture anatomical dissections and microscopic observations and to translate drawings into artworks for books and journals. By training and technical expertise, they introduced a particular kind of knowledge into scientific perception that also shaped the common image of nature. Illustrations of scientific publications, often undervalued as a biased interpretation of facts and subordinate to logic and description, thus convey an 'art history' of science in its own right, relevant both for the understanding of biological thought around 1800 as well as for the development of the arts and their historiography. The article is based on an analysis of botanical treatises produced for the Gottingen Society of Sciences in 1803, during an early phase of microscopic cell research, in order to determine the constitutive role of artistic knowledge and the media employed for the visualization and conceptualization of biological issues. PMID- 22035710 TI - Axes, planes and tubes, or the geometry of embryogenesis. AB - The paper presents selected figures of chick embryogenesis as depicted in the classic studies of Caspar Friedrich Wolff (1734-1794), Christian Heinrich Pander (1794-1865) and Karl Ernst von Baer (1792-1786). My main objective here is (1) to demonstrate how the imagery of Wolff, Pander and Baer attempted to project an image of a 3-dimensional rotating body into static figures on paper by means of linear contours, and (2) to ponder on the efficacy and pervasiveness of dots, lines and arrows for depicting embryogenesis. PMID- 22035711 TI - Inducing visibilities: an attempt at Santiago Ramon y Cajal's aesthetic epistemology. AB - In this paper, I consider Santiago Ramon y Cajal's strategy of histological observation and imaging in terms of what I call "induction of visibility" (Fiorentini, 2011). Cajal's strategy of visibility induction drew upon both rational and aesthetic visual sensibility, and considered this interplay to be a constitutive element of knowledge production. I propose to describe Cajal's fundamental attitude towards visually inferred knowledge in terms of an "aesthetic epistemology". PMID- 22035712 TI - Cellular dimensions and cell dynamics, or the difficulty over capturing time and space in the era of electron microscopy. AB - The introduction of electron microscopy profoundly altered biomedical research, providing a tool for a more detailed but at the same time a spatially and temporally more restricted visual analysis. Examining the case study of Golgi apparatus research in the 1950s and 1960s, it will be shown how microscopists handled these challenges, and how these confrontations modified the general concept of cellular organization. This will also shed light on the artifact debate and on the question of scientific realism in the field of microscopy. PMID- 22035713 TI - Cells from icons to symbols: molecularizing cell biology in the 1980s. AB - Over centuries cells have been the target of optical and electronic microscopes as well as others technologies, with distinctive types of visual output. Whilst optical technologies produce images 'evident to the eye', the electronic and especially the molecular create images that are more elusive to conceptualization and assessment. My study applies the semiotic approach to the production of images in cell biology to capture the shift from microscopic images to non traditional visual technologies around 1980. Here I argue that the visual shift that coincides with the growing dominance of molecular biology involves a change from iconic to symbolic forms. PMID- 22035714 TI - Standardizing psychotropic drugs and drug practices in the twentieth century: paradox of order and disorder. AB - According to ongoing historical research, standardizing the production and consumption of psychotropic drugs is a process fraught with contradictions and inconsistencies. Both the construction and change of drug standards can be highly unsettling events and do not necessarily lead to more order. The balance between order and disorder appears to be rather fragile and paradoxically at all stages in the evolution of standards we see order-disorder transitions. PMID- 22035715 TI - Blockbusters and controlled substances: Miltown, Quaalude, and consumer demand for drugs in postwar America. AB - In 1955 Carter Products launched its new tranquilizer Miltown with a huge marketing blitz; Miltown soon became one of America's earliest "blockbuster" celebrity drugs. In 1981, federal agents shut down a network of "stress clinics" and arrested the owners, medical staff, and other personnel for illegally trafficking in the sedative Quaalude; Quaalude soon became a "Schedule I Controlled Substance." Both of these stories are familiar, indeed archetypal, moments from America's postwar medical system. As the Miltown example reminds us, this fundamentally commercial system was built on the creation and courting of consumer demand for medical products and services, particularly drugs. As the Quaalude example shows, however, this system also incorporated tools for reining in excessive consumer demand. Together the two episodes affirm an enduring irony of the American medical system: the need for regulatory campaigns to tame lively markets for drugs that had become popular, in part, because of advertising campaigns. This article uses the Miltown and Quaalude sagas to explore the issue of consumer demand for prescription medicines, arguing that efforts to stoke or quash that demand have shaped (and linked) America's medical system and its drug control regimes. PMID- 22035716 TI - Naming the problem that has no name: creating targets for standardized drugs. AB - Many of the most common types of mental health problems that are found in outpatient psychiatric and general medical practices are diffuse, undifferentiated, and amorphous. Before the 1970s this lack of specificity did not conflict with the dominant theories and treatments of the American psychiatric profession or the demands of third party insurers and regulators. However, since that time the legitimacy and solvency of the psychiatric profession has come to depend on the perception that it treats specific disease entities. The establishment of the DSM-III in 1980 provided American psychiatry with many standardized disease entities that could be precisely measured, quantified, and abstracted from their particular contexts. In the late 1980s, these entities became the targets of the new class of psychoactive drugs, the Selective Serotonin Reuptake Inhibitors. Professional, political, economic, and cultural forces that arose in a particular historical era account for the standardization of mental illnesses. PMID- 22035717 TI - Reshaping chronicity: neuroleptics and changing meanings of therapy in French psychiatry, 1950-1975. AB - This article explores the transformations in the regime of practice and discourse concerning chronic mental illness in French psychiatry in the post-war period and the role played by chemotherapy in these transformations. From the 1950s and 60s on, chronicity was reconstructed as a new experience, involving a new set of expectations, of dilemmas and negotiations, and involving new types of actors giving a new meaning to what they were doing with patients. While some psychiatrists thought that neuroleptics could open the way to active treatment of these pathologies, in effect this project faced a series of obstacles: some came from psychiatric ideologies, others from the conditions of psychiatric work. As a result chronicity acquired a new uncertain and elusive shape. Based on an examination of the interplay of meaning and action in psychiatrists' recourse to neuroleptics in the treatment of their chronic patients, this article seeks to highlight the difficult construction of the idea of chemotherapy in post-war French psychiatry and, more generally, the transformations in its notion of therapy. PMID- 22035718 TI - The introduction of chlorpromazine in Belgium and the Netherlands (1951-1968); tango between old and new treatment features. AB - The introduction of chlorpromazine in Belgium and the Netherlands demonstrates an intriguing tango between old and new treatments. Chlorpromazine, marketed by the French company Rhone Poulenc entered psychiatry as an adjunct to existing therapies. Instead of promoting chlorpromazine as a revolutionary therapy, we see early efforts to market Largactil as a supplement to the armoury of psychiatric treatments. These marketing efforts matched the idiosyncrasies of national and local styles and cultures. Despite continuities with earlier therapeutic developments, we support the notion of a therapeutic revolution. In the early sixties supply and demand provoked a turn towards more standardized therapeutic regimes. PMID- 22035719 TI - East-Side story: the standardisation of psychotropic drugs at the Charite Psychiatric Clinic, 1955-1970. AB - The present article illustrates the history of psychotropic drugs introduced in the German Democratic Republic (GDR) from 1945 onwards. We begin by examining the introduction of an anti-depressant and a tranquilizer at the university psychiatric clinic, Charite, in East Berlin. On the basis of patient files, we consider the monitoring routines, altered by the use of psychotropic drugs, and the difficulties that arose when these routines were translated into existing research programs. In the 1960s, attempts to evaluate the psychiatric practice were based on psychopathology whereas at the end of the 1960s there was a shift to "target symptoms". PMID- 22035720 TI - Anatomy dissections and student experience at Irish universities, c.1900s-1960s. AB - Utilising the unique source of articles, poems, stories and cartoons from student magazines from all of the Irish universities, in addition to the memoirs of Irish doctors, and the accounts of correspondents, this paper will discuss the Irish student's experience of anatomy in the early twentieth century. For many medical students, anatomy dissections were seen as a rite of passage, while one student at Queen's College Belfast claimed that 'the dissecting-room is to the student a club, a smoke room, common room research room-one in all.' However, the dissecting rooms of Irish medical schools were often rife with bawdy conversation, sexual undertones and black humour. Recognising this, following the admission of women to Irish medical schools from the 1880s, university authorities constructed separate dissecting rooms for the women students, and part of this paper will investigate why this separation occurred. I will examine the Irish dissecting room as a centre of learning and integral part of student experience in the period. The paper will suggest that the black humour and pranks that were commonplace within the context of the dissecting room acted as a means for students to reconcile their fears and anxiety about dissecting. PMID- 22035721 TI - "Describing our whole experience": the statistical philosophies of W. F. R. Weldon and Karl Pearson. AB - There are two motivations commonly ascribed to historical actors for taking up statistics: to reduce complicated data to a mean value (e.g., Quetelet), and to take account of diversity (e.g., Galton). Different motivations will, it is assumed, lead to different methodological decisions in the practice of the statistical sciences. Karl Pearson and W. F. R. Weldon are generally seen as following directly in Galton's footsteps. I argue for two related theses in light of this standard interpretation, based on a reading of several sources in which Weldon, independently of Pearson, reflects on his own motivations. First, while Pearson does approach statistics from this "Galtonian" perspective, he is, consistent with his positivist philosophy of science, utilizing statistics to simplify the highly variable data of biology. Weldon, on the other hand, is brought to statistics by a rich empiricism and a desire to preserve the diversity of biological data. Secondly, we have here a counterexample to the claim that divergence in motivation will lead to a corresponding separation in methodology. Pearson and Weldon, despite embracing biometry for different reasons, settled on precisely the same set of statistical tools for the investigation of evolution. PMID- 22035722 TI - Ethnology in the metropole: Robert Knox, Robert Gordon Latham and local sites of observational training. AB - Anthropologists have traditionally separated the history of their discipline into two main diverging methodological paradigms: nineteenth-century armchair theorizing, and twentieth-century field-based research. But this tradition obscures both the complexity of the observational practices of early nineteenth century researchers and the high degree of continuity between these practices and the techniques that came later. While historians have long since abandoned the notion that nineteenth-century ethnologists and anthropologists were merely 'armchair' theorists, this paper shows that there is still much to learn once one asks more insistently what the observational practices of early researchers were actually like. By way of bringing out this complexity and continuity, this essay re-examines the work of two well-known British ethnologists, Robert Knox, and Robert Gordon Latham; looking in particular at their methods of observing, analysing and representing different racial groups. In the work of each figure, early training in natural history, anatomy and physiology can be seen to have influenced their observational practices when it came to identifying and classifying human varieties. Moreover, in both cases, Knox and Latham developed locally-based observational training sites. PMID- 22035723 TI - Is meta-analysis the platinum standard of evidence? AB - An astonishing volume and diversity of evidence is available for many hypotheses in the biomedical and social sciences. Some of this evidence-usually from randomized controlled trials (RCTs)-is amalgamated by meta-analysis. Despite the ongoing debate regarding whether or not RCTs are the 'gold-standard' of evidence, it is usually meta-analysis which is considered the best source of evidence: meta analysis is thought by many to be the platinum standard of evidence. However, I argue that meta-analysis falls far short of that standard. Different meta analyses of the same evidence can reach contradictory conclusions. Meta-analysis fails to provide objective grounds for intersubjective assessments of hypotheses because numerous decisions must be made when performing a meta-analysis which allow wide latitude for subjective idiosyncrasies to influence its outcome. I end by suggesting that an older tradition of evidence in medicine-the plurality of reasoning strategies appealed to by the epidemiologist Sir Bradford Hill-is a superior strategy for assessing a large volume and diversity of evidence. PMID- 22035724 TI - Morphogenesis, Dictyostelium, and the search for shared developmental processes. AB - In the 1930s John Tyler Bonner began studying the slime mold, Dictyostelium discoideum, as a way to investigate how organisms develop. With a life cycle that includes periods of unicellularity and multicellularity, Dictyostelium raises questions fundamental to development and evolution. In Morphogenesis: An Essay on Development (1952), Bonner built on his work with Dictyostelium to inform developmental theory and practice. By exploring how Bonner's early work with Dictyostelium motivated his synthetic approach in Morphogenesis, this paper presents an example of how those who studied development sought ways to gain traction in the rapidly changing life sciences. While a biochemical viewpoint of development became dominant, morphogenesis provided a way to reintroduce and emphasize biological organization at the organismal level. Bonner's early work offers a window to mid-twentieth century studies of development, an understudied area in the history of science, and shows that it was a time when growing experimental evidence enabled new ways of thinking about the relationship between ontogeny and evolution, and more broadly, about how the parts of nature might fit together. PMID- 22035725 TI - Cognitive individualism and the child as scientist program. AB - In this paper, I examine the charge that Gopnik and Meltzoff's 'Child as Scientist' program, outlined and defended in their 1997 book Words, Thoughts and Theories is vitiated by a form of 'cognitive individualism' about science. Although this charge has often been leveled at Gopnik and Meltzoff's work, it has rarely been developed in any detail. I suggest that we should distinguish between two forms of cognitive individualism which I refer to as 'ontic' and 'epistemic' cognitive individualism (OCI and ECI respectively). I then argue - contra Ronald Giere - that Gopnik and Meltzoff's commitment to OCI is relatively unproblematic, since it is an easily detachable part of their view. By contrast, and despite their explicit discussion of the issue, their commitment to ECI is much more problematic. PMID- 22035726 TI - Infectious milk: issues of pathogenic certainty within ideational regimes and their biopolitical implications. AB - Throughout the 19(th) century and early decades of the 20(th) century, milk was a dangerous food that required state intervention to make it safe. Throughout this period, the germ theory of contagious disease came to prominence, but could not explicitly determine the causal relationships linking germs, milk, and human illness. Using the notion of an ideational regime, I examine how (1) knowledge claims move from uncertainty to certainty and become privileged claims within ideational regimes that (2) result in an unintended, but necessary deployment of a biopolitical strategy for governance. The argument here is that theoretical uncertainty meant managing populations as a uniform undifferentiated reality using pasteurization technologies. I use two historical moments as evidence of these processes. The first is the 1901 British Congress on Tuberculosis when I argue germ theory came to a theoretical standstill and the second is Ontario's 1938 amendment to the province's Public Health Act that permanently institutionalised province-wide compulsory pasteurisation laws organised around the notion of nutritional equivalency. This genealogical exploration should provide some insight into how bacteria became the singular cause of illness and into the conditions that led to targeting milk as the main site of intervention instead of treating individual bodies. PMID- 22035727 TI - Complex systems, evolution, and animal models. AB - In this paper, we respond to arguments made concerning our position regarding animal models (Shelley, 2010) by briefly examining the fact that animals (human and nonhuman) are complex systems that have different evolutionary trajectories. This historical fact has implications for using animals as predictive models for human response to drugs and disease. PMID- 22035728 TI - [Carpal tunnel syndrome surgery in France in 2008: patients' characteristics and management]. AB - INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common upper limb neuropathy. There has been a dramatic increase in CTS surgery since the 1990s. This study focuses on changing incidence of CTS surgery in France and associated factors. PATIENTS AND METHOD: Cases of CTS surgery were identified using the national hospital discharge database for persons living in metropolitan France. Patient characteristics, comorbidities and care management were studied using the reimbursement database of the beneficiaries covered by the general health insurance scheme (76% of the 64-million French population) comparing those with or without CTS surgery in 2008. RESULTS: In 2008, hospital admissions for CTS surgery were identified in 127,269 patients aged 20 years and older, giving an overall incidence of 2.7/1000 (females 3.6/1000, males 1.7/1000) in metropolitan France. Between 1999 and 2008, the number of patients with CTS surgery increased 25%. Half of this increase was directly related to increasing demographics. For people in the 20 to 59-year age range, incidences were respectively 2.5/1000, 3.6/1000 and 1.3/1000 with high regional variations (1.1/1000-5.5/1000). Individuals aged 60 years and older accounted for 36% of the patients. Using a negative binomial regression, regional incidence variation was significantly and positively associated with the regional density of surgeons practising CTS surgery, proportion of manual workers in the population and proportion of employment in the industrial sector and negatively associated with densities of primary care physicians, rheumatologists and physiotherapists. Certain comorbidities were found to be significantly associated with CTS surgery: diabetes mellitus (Relative Risk [RR]=1.6), hypothyroidism (RR=1.3), end-stage renal disease treated with dialysis (RR=3.3), depression (RR=1.5), hereditary metabolic disease (RR=1.3), ankylosing spondylosis (RR=1.5). Interestingly, a significant negative association was found for full healthcare coverage linked with very low income (RR=0.7) and certain chronic diseases: Alzheimer's disease (RR=0.3), Parkinson's disease (RR=0.7), neuroleptic medications (RR=0.4), multiple sclerosis (RR=0.7). This could be associated with lower frequency of occupational risk factors and a lack of complaint or investigation. After surgery, 55.0% of the patients in the 18 to 59 years age range had a period of sick leave and 36.8% returned to work later than the upper limit of the recommended recovery period of 56 days. The annual cost of sick leaves was estimated at 81 million euros for the general health insurance scheme. CONCLUSION: The number of CTS surgical procedures is increasing in France. Prevention of CTS in the workplace must be sustained and encouraged. Recommendations for sick leave periods should be followed. PMID- 22035729 TI - Are varicoceles associated with increased deoxyribonucleic acid fragmentation? AB - OBJECTIVE: To perform a literature search on the association between varicocele and sperm DNA fragmentation. DESIGN: Systematic review. PATIENT(S): Men with a varicocele and infertility. INTERVENTION(S): Varicocele repair. MAIN OUTCOME MEASURE(S): Does the presence of a varicocele increase seminal oxidative stress and sperm DNA fragmentation? RESULT(S): In men with a varicocele increased levels of reactive oxygen species and sperm DNA damage can be found. This is probably related to defective spermatogenesis in these patients. Seminal oxidative stress is believed to be the source of sperm DNA damage. Patients with a varicocele and oligospermia may also have a diminished seminal antioxidant capacity. After varicocele repair sperm DNA fragmentation decreases. CONCLUSION(S): Varicocele is associated with sperm DNA damage, and this sperm pathology may be secondary to varicocele-mediated oxidative stress. The beneficial effect of varicocelectomy on sperm DNA damage further supports the premise that varicocele may impair sperm DNA integrity. PMID- 22035730 TI - Expression of BET genes in testis of men with different spermatogenic impairments. AB - OBJECTIVE: To characterize the BET gene expression in human testis with spermatogenetic impairments; to examine BRDT protein expression in testis and semen. DESIGN: Prospective study. SETTING: Fertility clinic. PATIENT(S): Azoospermic men (n = 120) who underwent testicular sperm extraction and who were classified as either normal spermatogenesis, mixed atrophy, spermatocyte maturation arrest, or Sertoli cells only according to their combined histologic and cytologic testicular findings and three normozoospermic men who donated sperm. INTERVENTION(S): Evaluation of testicular biopsies by qualitative and quantitative reverse transcriptase-polymerase chain reaction, immunohistochemical staining, and analysis of spermatozoa by immunofluorescence. MAIN OUTCOME MEASURE(S): Expression of the four BET genes in testis and localization of BRDT protein in testicular tissue and ejaculated spermatozoa. RESULT(S): The BRDT gene was not expressed in testicular tissue from patients with Sertoli cells only, whereas the other three genes of the BET family retained expression in all the pathologies. The BRDT protein was localized in the nuclei of spermatocytes, spermatids, and ejaculated spermatozoa. Expression of BRDT protein was almost nil in testicular tissue specimens with spermatocyte maturation arrest despite normal transcript levels. CONCLUSION(S): Human BRDT expression pattern differs from mouse BRDT expression. In human, BRDT is the only BET gene expressed exclusively in testicular germ cells. Its expression in elongated spermatids and ejaculated spermatozoa raises the possibility that it is involved in unidentified additional functions. PMID- 22035732 TI - [Which patent foramen ovale needs to be closed, and how?]. AB - Patent Foramen Ovale (PFO) is a normal fetal communication between right and left atria that persists after birth by about 30% in adults. It is discussed to be associated to potential clinical events, asking rational of such closure. Its correction throughout venous access can be attempted on four different indications: (1) secondary prevention of stroke or transient ischemic attack, (2) decompression illness, (3) migraine with aura, and (4) platypnea-orthodeoxia. The PFO closure procedure implies the double control of X-rays and ultrasound, and is relatively simple to perform, using various prostheses. In France, the place of percutaneous closure procedure is nowadays unclear since the Haute Autorite de sante currently suspended recommendations about the management after stroke. PMID- 22035731 TI - The prevalence of digenic mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome. AB - OBJECTIVE: To determine the prevalence of digenic mutations in patients with idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS). DESIGN: Molecular analysis of DNA in IHH/KS patients. SETTING: Academic medical center. PATIENT(S): Twenty-four IHH/KS patients with a known mutation (group 1) and 24 IHH/KS patients with no known mutation (group 2). INTERVENTION(S): DNA from IHH/KS patients was subjected to polymerase chain reaction-based DNA sequencing of the 13 most common genes (KAL1, GNRHR, FGFR1, KISS1R, TAC3, TACR3, FGF8, PROKR2, PROK2, CHD7, NELF, GNRH1, and WDR11). MAIN OUTCOME MEASURE(S): The identification of mutations absent in >=188 ethnically matched controls. Both SIFT (sorting intolerant from tolerant) and conservation among orthologs provided supportive evidence for pathologic roles. RESULT(S): In group 1, 6 (25%) of 24 IHH/KS patients had a heterozygous mutation in a second gene, and in group 2, 13 (54.2%) of 24 had a mutation in at least one gene, but none had digenic mutations. In group 2, 7 (29.2%) of 24 had a mutation considered sufficient to cause the phenotype. CONCLUSION(S): When the 13 most common IHH/KS genes are studied, the overall prevalence of digenic gene mutations in IHH/KS was 12.5%. In addition, approximately 30% of patients without a known mutation had a mutation in a single gene. With the current state of knowledge, these findings suggest that most IHH/KS patients have a monogenic etiology. PMID- 22035734 TI - Membrane trafficking and cytoskeletal dynamics in neuronal function. PMID- 22035733 TI - Genome-wide association studies in plants: the missing heritability is in the field. AB - Genome-wide association studies (GWAS) have been even more successful in plants than in humans. Mapping approaches can be extended to dissect adaptive genetic variation from structured background variation in an ecological context. PMID- 22035735 TI - Apathy and impulse control disorders in Parkinson's disease: a direct comparison. AB - BACKGROUND: Apathy and impulse control disorders (ICDs) in Parkinson's disease (PD) are clinically important complications and may exist on a common behavioral spectrum of disorders of reward and motivation. OBJECTIVE: To directly compare PD participants with apathy those with ICDs on range of demographic, neurologic and psychiatric measures. METHODS: Ninety-nine non-demented PD participants (ICD, n = 35; apathy, n = 26; and controls, n = 38) were assessed in the study. Univariate statistics were used to compare the behavioral groups. A linear regression model was created with either apathy or impulsivity as the dependent variable. RESULTS: The two behavioral groups differed significantly from the PD control group on similar factors but in opposite directions. The apathy group was older at the time of both assessment and disease onset, had higher levels of depression and lower dopamine agonist use, compared to the other two groups. The ICD group was younger than the apathy group at disease onset and had higher levels of anxiety, a higher overall dopamine load and greater motor disease complexity. Overlap in behavioral pathology across the two groups was also noted. CONCLUSION: Apathy and ICDs may be on a common behavioral spectrum in PD. Both are associated with significant psychiatric morbidity supporting shared underlying pathology. PMID- 22035736 TI - Retrospect of hematologic malignancies 2010. PMID- 22035737 TI - Unusual autoimmune nonhematologic complications in chronic lymphocytic leukemia. AB - Autoimmune phenomena are well known to complicate chronic lymphocytic leukemia (CLL) and occur in 10% to 25% of patients. Hematologic autoimmune complications, particularly autoimmune hemolytic anemia and immune thrombocytopenia, are much more common than nonhematologic complications. We present 6 cases of patients who exhibited uncommon complications of CLL: myasthenia gravis, acquired von Willebrand disease, bullous pemphigoid, and acquired angioedema. In our patients, the activity and recrudescences of these complications were highly associated with CLL remission or progression. More awareness of the association of CLL with these complications could facilitate earlier diagnosis and effective treatment. PMID- 22035739 TI - Dasatinib combined with interferon-alfa induces a complete cytogenetic response and major molecular response in a patient with chronic myelogenous leukemia harboring the T315I BCR-ABL1 mutation. AB - Mutations of BCR-ABL1 are observed in 50% of patients with imatinib-resistant chronic myeloid leukemia (CML). The T315I mutation is resistant to imatinib and second-generation tyrosine kinase inhibitors (TKIs). We report the case of a 57 year-old man diagnosed with CML in 2003 in whom imatinib therapy failed after which he acquired the T315I mutation. He was treated sequentially with an anti T315I-specific agent, KW-2449, that led to eradication of the mutation without any further improvement. Subsequent introduction of combination therapy that included dasatinib and pegylated interferon led to the achievement of a sustained complete cytogenetic and major molecular response (MMR). This case illustrates the benefit of combination therapy that includes a TKI and a second agent with a different mechanism of action, either sequentially (TKI followed by KW-2449) or concomitantly (TKI + interferon), in eradicating resistant disease with the T315I clone. PMID- 22035740 TI - A comparison of races and leukemia subtypes among patients in different cancer survivorship phases. AB - BACKGROUND: The three phases of cancer survivorship include the acute survival phase (ASP), the extended survival phase (ESP), and the permanent survival phase (PSP). This Institutional Review Board-approved retrospective pilot project compared races and leukemia subtypes among patients in the ASP, ESP, and PSP. METHODS: Fifty-five adult patients from our National Cancer Institute-designated cancer center were individually interviewed. Subjects were asked about multiple areas of survivorship including their social support system, distress level, and quality of life. RESULTS: Demographics of the 55 patients are acute lymphocytic leukemia (ALL), 10; acute myelocytic leukemia (AML), 9; chronic lymphocytic leukemia (CLL), 23; and chronic myelocytic leukemia (CML), 13. There were 23 females and 32 males, 30 Hispanics, 20 Caucasians, and 5 African-Americans. Twenty-two patients were in the ASP, 21 in the ESP, and 12 in the PSP. AML patients experienced the most physical, family, emotional, and spiritual problems (78%, 33%, 56%, and 22%, respectively). AML patients also had the highest distress level with a mean score of 5.8 (SD 1.7), compared to ALL (1.8), CLL (3.2), and CML (5.1) (P value < .001). Among all the phases of survivorship, the ASP had the highest distress level (mean, 4.8) and the worst quality of life (mean, 2.3). The ASP patients had the most treatment for depression (38%). When comparing races, African Americans and Hispanics (40% and 37%, respectively) were unable to cope with finances, compared to Caucasians (5%), (P value .016). Fear of recurrence was higher in Hispanics (67%), compared to African Americans (40%) and Caucasians (30%) (P value .031). Hispanics (40%) experienced more problems with housing, insurance, and work, as compared to African Americans (20%) and Caucasians (10%) (P value .047). CONCLUSION: This study addresses the perceptions and beliefs of leukemia survivors and found that AML and minority patients need further investigation on various aspects of quality of life. PMID- 22035738 TI - Outcome of treatment of chronic myeloid leukemia with second-generation tyrosine kinase inhibitors after imatinib failure. AB - Although imatinib revolutionized the management of chronic myeloid leukemia (CML), recent data indicate a transformation in the treatment approach likely in the near future. For patients whose CML does not respond to standard-dose imatinib therapy, increasing the imatinib dose is a second-line option. However, high-dose imatinib is not an appropriate approach for patients experiencing drug toxicity, and there remain questions concerning the durability of responses achieved with this strategy. Alternative second-line options include the newer tyrosine kinase inhibitors (TKIs) such as dasatinib and nilotinib. A substantial amount of long-term data for these agents is available. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. The superiority of second generation TKIs over imatinib in newly diagnosed disease has been recognized as well. They induce high and rapid rates of cytogenetic and molecular response, with less progression to advanced forms of disease in comparison with imatinib. Several investigational agents specific for those patients with the T315I mutation remain under evaluation. The future of CML therapy may include early use of these potent agents to help more patients achieve molecular remission and potentially be a path to a CML cure. PMID- 22035741 TI - Fatal paraneoplastic systemic leukocytoclastic vasculitis as a presenting feature of chronic lymphocytic leukemia. AB - BACKGROUND: The most common paraneoplastic vasculitis is leukocytoclastic vasculitis (LCV),(1) 75% of which are caused by hematological malignancies. Chronic lymphocytic leukemia (CLL) is associated with a multitude of auto-immune paraneoplastic syndromes. Data on LCV in association with CLL is restricted to isolated case reports,(3,4) none of which had systemic LCV. We present a unique case of fatal paraneoplastic, systemic LCV as an initial presentation of CLL in an elderly male with multiple co-morbidities. CASE: A 71-year-old man presented with a palpable, symmetric, purpuric rash on the lower extremities and an absolute lymphocytosis (white blood cell count 26.9; 23% lymphocytes). His co morbidities included coronary artery disease, congestive heart failure, and new critical aortic stenosis. Flow cytometry of peripheral blood demonstrated an abnormal population of B-cells, positive for CD5, CD19, and CD23, consistent with CLL. The skin biopsy specimen revealed neutrophilic inflammation in vessel walls indicative of LCV. Acute renal failure (creatinine 2 mg/dL), urinary red cell casts, and hypocomplementemia were concerning for a systemic vasculitis. The antinuclear antibody, cryoglobulin titer, antineutrophil cytoplasmic antibody, serum protein electrophoresis, viral serologies were negative. On hospital day 6, he developed acute hepatocellular injury and acute respiratory failure. Continuous veno-venous hemodialysis was begun for worsening acidemia and hyperkalemia. Two days later he became obtunded on hospital day 8 and had an elevated lactic acid level with generalized abdominal tenderness worrisome for bowel ischemia. The same day he needed intubation with cardiopulmonary resuscitation for a brief episode of asystole. Despite aggressive treatment with high-dose steroids and plasmapheresis, he suffered worsening renal failure and shock. His family sought withdrawal of care on hospital day 11. Autopsy revealed diffuse LCV of the stomach, distal ileum, integument and alveoli with petechial hemorrhages, fibrin thrombi, and gangrenous patchy necrosis. CONCLUSION: Paraneoplastic LCV is a rare syndrome and seldom occurs in association with CLL. This is the first reported case of fatal systemic paraneoplastic LCV from B-cell CLL. Dermatologic involvement is universal with LCV, and may portend systemic disease. More data on its pathogenesis in CLL is warranted. PMID- 22035742 TI - Array comparative genomic hybridization analysis identifies recurrent gain of chromosome 2p25.3 involving the ACP1 and MYCN genes in chronic lymphocytic leukemia. AB - Chromosomal aberrations are independent prognostic markers in chronic lymphocytic leukemia (CLL). Recent studies using genomic arrays have shown recurrent gains of the short arm of chromosome 2 (2p) in a subset of CLL. We evaluated 178 CLL cases for 2p gains using custom-designed oligonucleotide array-based comparative genomic hybridization (aCGH). A high frequency of 2p gains was observed in 53 of 178 (30%) cases, which ranged from a small 29-kb region to large segments involving the entire short arm. Besides several common chromosomal aberrations associated with 2p gain, we demonstrated a novel observation that gain of the telomeric region 2p25.3 harboring the ACP1 gene is common in CLL (25%, 44 of 178 cases). The ACP1 gene has been previously shown to regulate T-cell receptor signaling through ZAP-70, and both genes are unfavorable clinical markers for CLL. Quantitative polymerase chain reaction (qPCR) confirmed the presence of 3-6 copies of ACP1 in 35 of 40 (88%) of these cases. Interestingly, none of the aCGH diploid CLL cases showed gain of ACP1. Assessment of 73 healthy individuals by qPCR revealed ACP1 copy number gain in only two cases (2.7%). Gain of 2p25.3 was associated with ZAP-70 expression (P < .002) and unmutated immunoglobulin heavy chain variable (IGHV) gene mutation (P < .0001). A high frequency of MYCN co amplication with ACP1 was observed (14 of 40 cases, 35%). The frequent 2p25.3 gain involving the ACP1 and MYCN genes may help define the critical region of 2p that contributes to pathogenesis of CLL together with other chromosomal abnormalities. PMID- 22035743 TI - Chlorambucil--still not bad: a reappraisal. AB - Although chlorambucil has been used in the management of chronic lymphocytic leukemia (CLL) for 55 years, the optimal dose and treatment duration have not been established. We summarized data from 4 UK randomized CLL trials over the past 30 years in which chlorambucil, as a single agent, was one of the study arms. Overall response rates (ORR) ranged from 57% to 75% when using doses of 60 70 mg/m(2) per 28-day cycle. This compares favorably with an ORR of 31% to 55% in other studies that used lower doses. Response rates improved when patients received 6 or more courses. Studies that used chlorambucil as a comparator, at lower doses or with fewer courses, resulted in consistently lower ORR. Comparisons with single-agent fludarabine in 2 randomized trials (LRF CLL4 and German CLL5) showed similar progression-free survival. Chlorambucil compares favorably with fludarabine and bendamustine with respect to myelotoxicity, neutropenia, and fever, even at 70 mg/m(2) per cycle and in the elderly. Resistance to chlorambucil does not preclude a good response to newer treatments used as second-line treatment, which explains the good survival after progression observed in patients randomized to chlorambucil in LRF CLL4. Chlorambucil is currently being combined with anti-CD20 monoclonal antibodies in several phase II and III trials. It remains a useful drug for patients unfit to receive more intensive combinations. However, both the dose and duration of treatment are important. PMID- 22035744 TI - Prognostic factors and models in polycythemia vera, essential thrombocythemia, and primary myelofibrosis. AB - Myeloproliferative neoplasms include essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). These 3 diseases have common clinical features, such as a high risk of vascular complications, progression to secondary myelofibrosis, and clonal evolution into the blast phase. Current risk factors of ET and PV, used to predict events, are patient based: age >60 years and a history of thrombosis. Very recently, other parameters, such as leukocyte count and the presence of JAK2 (V617F) mutation, have been reported as potential risk factors. Prognosis in PMF is predicted at diagnosis by a combination of different risk factors, such as advanced age (age >60 years), anemia, leukocytosis (white blood cell count > 25 * 10(9)/L), the presence of blast cells (>= 1%), and the presence of constitutional symptoms. This model may also predict survival when applied during follow-up. PMID- 22035746 TI - BCR-ABL1--negative myeloproliferative neoplasms: a review of molecular biology, diagnosis, and treatment. AB - In 2008, the World Health Organization expanded the classification of myeloproliferative disorders based on increasing amounts of molecular and cytogenetic data. Myeloproliferative neoplasms (MPN) that do not contain the BCR ABL1 mutation include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). JAK2V617F is the best characterized mutation in BCR ABL1-negative neoplasms, with an estimated prevalence of more than 95% in PV, 50% in ET, and 50% in PMF. Current diagnostic strategies are increasingly reliant on molecular markers, and their prognostic value continues to be investigated. The use of aspirin, hydroxyurea, and phlebotomy for PV and ET, and the use of androgens, steroids, chemotherapy, and radiation therapy for PMF continues to be the mainstay of therapy. The only potentially curative therapy is allogeneic hematopoietic stem cell transplantation, but treatment-related mortality remains high. There have been promising results from clinical trials that involve the JAK tyrosine kinase inhibitors TG101384 and INCB018424, but their role in future therapy is yet to be established. Despite the optimism, it is increasingly apparent that pathogenicity in BCR-ABL1-negative MPN is more complex than for chronic myeloid leukemia, and a pathognomonic mutation may not be forthcoming. PMID- 22035745 TI - JAK2 inhibitors: are they the solution? AB - The discovery of the JAK2V617F mutation in patients with Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) started the era of targeted therapy for these diseases. Until now, patients had few treatment options available, which usually were restricted to hydroxyurea, interferon preparations, and chemotherapy in more aggressive cases. JAK2 inhibitors have been developed over the past 5 years, and the results of the first clinical trials with JAK2 inhibitors for patients with myelofibrosis were recently published. Current research results suggest that JAK2 inhibitors have a potential to decrease disease burden and its activity, as manifested by a decrease in splenomegaly and improvement in systemic disease-related symptoms, but they do not seem to be able to eradicate the malignant clone. However, JAK2 inhibitors help patients regardless of their mutation status, because patients without JAK2V617F mutation benefit to the same extent as patients with JAK2V617F mutation. A greater understanding of the pathophysiology of MPNs is needed before we can cure myelofibrosis with drug therapy. Currently, several new JAK2 inhibitors are in clinical trials for patients with myelofibrosis, and clinical trials for patients with polycythemia vera and essential thrombocythemia have also started. We review recent data on JAK2 inhibitors for the management of patients with Ph-negative MPNs. PMID- 22035747 TI - Allogeneic stem cell transplantation for myelodysplastic syndromes: critical for cure? AB - Allogeneic stem cell transplantation (SCT) is the treatment of choice for young patients (age <= 55 years) with myelodysplastic syndromes (MDS) characterized by poor-risk or intermediate-risk cytogenetics, who have a histocompatible related or unrelated donor. For patients who lack an human leukocyte antigen-compatible donor, autologous SCT, or chemotherapy may be good alternatives for those with MDS and with good-risk cytogenetic characteristics. Iron toxicity is an underestimated cause of hematopoietic stem cell transplantation (HSCT) treatment related mortality. The pathogenesis, diagnosis, and monitoring of iron-induced organ damage are currently topics of investigation. Prospective studies on the prevention or treatment of iron toxicity before HSCT and/or after HSCT are necessary. PMID- 22035748 TI - Monitoring of minimal residual disease in acute myeloid leukemia: methods and best applications. AB - Posttherapy minimal residual disease assessment in acute myeloid leukemia is an important prognostic indicator as well as a potential early surrogate measure of therapeutic effectiveness. The goal of this brief review is to discuss the broad classes of targets for molecular diagnostic assays, with specific examples of each, and to describe the analytic approach to flow cytometry testing for minimal residual disease in acute myeloid leukemia. Several of the most significant recent contributions to this field are highlighted. PMID- 22035749 TI - Older patients with acute myeloid leukemia benefit from intensive chemotherapy: an update from the Swedish Acute Leukemia Registry. AB - Most patients with acute myeloid leukemia (AML) are older, the median age is 71 years, and survival decreases rapidly with age. The achievement of complete remission and long-term survival mostly require intensive combination chemotherapy, but standard regimens are often believed to be too toxic for older patients. The Swedish Acute Leukemia Registry is unique and contains data on 98% of all patients diagnosed since 1997, irrespective of management. Comorbidity increases with age, but the distribution of AML-related risk factors is mostly similar in different age groups of patients older than 60 years old. In Sweden, most patients up to 75 years old are given intensive induction treatment with acceptable complete remission rates. Early death rates were always lower with intensive treatment compared with palliative treatment, thus, most patients up to 75 years and with AML both tolerate and benefit from intensive induction treatment. PMID- 22035750 TI - New treatments and strategies in acute myeloid leukemia. AB - Despite considerable progress in the treatment of acute myeloid leukemia in the past several decades, the prognosis of the majority of patients with this disease remains guarded. Advances in supportive care and better characterization of disease subsets through cytogenetics and molecular analysis have led to significant success in treating specific subsets of patients, such as those with acute promyelocytic leukemia and core binding factor leukemias, particularly among the younger patients who are able to better tolerate the effects of cytotoxic chemotherapy. However, overall, only about 40% of younger patients and <10% of older patients with this disease are alive at 5 years. Current research is focusing on the identification of new cellular targets amenable to specific inhibitors, designing the best strategies for combining these novel agents with traditional chemotherapy regimens, and determining prognostic indicators that may allow us to better stratify therapy. PMID- 22035751 TI - Targeting the bone marrow in Waldenstrom macroglobulinemia. AB - Waldenstrom macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by widespread involvement of the bone marrow with lymphoplasmacytic cells. In approximately 20% of patients, the malignant clone also involves the lymph nodes and induces hepatosplenomegaly. The mechanisms by which the tumor cells home to the bone marrow and preferentially reside in the marrow niches are not fully elucidated. In this review, we examine the role of the bone marrow microenvironment in the regulation of cell growth, survival and cell dissemination in WM. We also summarize specific regulators of niche-dependent tumor proliferation in WM. These include chemokines, adhesion molecules, Src/PI3K/Akt/mTOR signaling, NF-kB activation, and micro-RNA regulation in WM. Targeting these pathways in clinical trials could lead to significant responses in this rare disease. PMID- 22035752 TI - Fludarabine versus chlorambucil: is the debate over? AB - Historically, chlorambucil had been considered to be the treatment of choice for previously untreated patients with chronic lymphocytic leukemia (CLL) from the 1950's until 1990's. Ever since the 1990's, when the nucleoside analogue, fludarabine, became available as a therapeutic agent, this drug has replaced chlorambucil in the treatment of CLL. In the initial treatment of CLL. Although, prospectively conducted, randomized clinical trials comparing these two drugs in the front-line therapy of CLL, initially, showed a significant increase in the complete remission rates, overall remission rates, and progression-free-survival in patients treated with fludarabine, as compared to the patients treated with chlorambucil, the overall survival duration did not show a significant improvement improvement. A recent report, of a long-term follow-up of that study now reveals that a significant increase in the overall survival time of the patients who, originally, were randomized to fludarabine arm started to become manifest only after about 6 years had passed from the time of first treatment on this study. Thus, fludarabine has now been proven to be superior to chlorambucil for the initial treatment of CLL. PMID- 22035753 TI - High-risk multiple myeloma: does it still exist? AB - Major improvement milestones in the treatment of patients with multiple myeloma (MM) include the introduction of the melphalan/prednisone combination in the 1960s, high-dose chemotherapy supported by autologous stem cell transplant in the 1980s, and the more recent introduction of the novel agents thalidomide, lenalidomide, and bortezomib. Historically, age and eligibility for autologous stem cell transplantation were the primary basis for treatment selection, but, from a biologic standpoint, MM therapy was "one size fits all," in that therapy was not tailored based on molecular or other features that define subtypes of MM. Recently, novel therapies have extended overall survival for the broad spectrum of patients with myeloma. Moreover, newer data demonstrate that novel therapies may ameliorate the prognostic impact of predictors of high risk and poor outcome in MM, which suggests that patients with MM and with high-risk disease should receive novel agents. Such approaches may constitute nascent steps toward individualized therapy, ie, the selection of highly effective therapies based on specific features exhibited by an individual patient's MM. However, prospective data that demonstrate the validity of these approaches are lacking. Definitive, multi-institutional clinical trials are required before redefining standards of myeloma care based on this approach. PMID- 22035754 TI - HSP90 inhibitors as therapy for multiple myeloma. AB - The heat shock protein 90 (HSP90) family of proteins are ubiquitous molecular chaperones that are intricately involved in folding, activation, maturation, and assembly of many proteins that include essential mediators of signal transduction and cell cycle progression. They are abundant in eukaryotic cells and localized to the cytoplasm and mitochondria as well as the endoplasmic reticulum under normal conditions, making up 1% to 2% of all cellular proteins. HSP90 proteins have increased expression in a number of malignancies, including multiple myeloma. HSP90 inhibition can influence multiple oncogenic pathways and proteins involved in myeloma, therefore making it an attractive target for drug development in this disease. This article serves as an overview of the pre clinical data and clinical trial data on HSP90 inhibitors in multiple myeloma. PMID- 22035755 TI - Management of myeloma: an Italian perspective. AB - Multiple myeloma remains a fatal plasma cell malignancy. However, new insights into the disease biology and immunology have identified molecular mechanisms, underling functional interactions between plasma cells and the bone marrow microenvironment that have become molecular targets of so-called "new drugs" such as thalidomide, lenalidomide, and bortezomib. Recently, the combinations of new drugs with melphalan and prednisone in elderly patients, and with autologous stem cell transplantation in induction and/or maintenance schedules in younger patients have significantly prolonged overall survival. Optimal combinations and timing are a matter of debate. Moreover, management of side effects is a key clinical target to improve long-term quality of life. Many randomized phase III studies are currently in progress to address these issues. Whether these new advancements in myeloma treatment will eventually translate into a long chronic phase or a monoclonal gammopathy of undetermined significance-like status for the majority of patients remains, however, still unanswered. PMID- 22035756 TI - Non-Hodgkin's lymphoma: the old and the new. AB - During the past decade we have witnessed a number of changes in the field of non Hodgkin lymphoma (NHL), including new entities added to the classification as well as a better understanding of the biology of diffuse large B-cell lymphoma (DLBCL). An understanding of the epigenetics of NHL is also contributing new agents for the management of this disorder. It has become increasingly clear that DLBCL is a biologically and clinically heterogeneous cell type. Two major categories are now recognized: germinal center B cell and activated B-cell (ABC) types. The former is associated with a good prognosis while the latter is known to have a more adverse outcome. With the use of routine immunohistochemical stains, these two types can be identified. The ABC type is known to be NFK-B dependent. NFK-B is a therapeutic target for bortezomib which is being investigated as treatment for this subtype of DLBCL. Several major changes in the classification will be discussed among which the most important are the recognition of so-called borderline entities. One of the two most common of these is the borderline DLBCL/Burkitt tumor (DLBCL/BL) which has features of both DLBCL and Burkitt's lymphoma. Many of the cases in this DLBCL/BL category contain a translocation of MYC as well as BCL2, so-called "double-hit lymphomas" which have a very aggressive clinical behavior. The second common borderline entity is the mediastinal grey zone NHL (MGZL) which has pathological features intermediate between primary mediastinal B-cell lymphoma and nodular sclerosing Hodgkin lymphoma (NSHL). Overlapping clinical features include young age, male predominance, and localized mediastinal presentation. Anecdotal reports suggest MGZL is relatively resistant to Hodgkin-based chemotherapy. Epigenetic therapy represents a new concept. Histone deacetylase inhibitors (HDACi)and DNA methyltransferase inhibitors constitute a promising new class of antineoplastic agents. They modify the expression of genes related to cancer development. In this review, we discuss the role of HDACi in lymphomagenesis as well as in treatment. To understand the benefits of HDACi in lymphoma treatment, we must appreciate the crucial interplay between BCL6, p53, and STAT3. The STAT3 oncogene is involved in the ABC type of DLBCL, an unfavorable and frequently therapy refractory lymphoma. STAT3 can be effectively suppressed by several HDACi. We will summarize the results of recent trials with HDACi such as romidepsin, panobinostat and valproic acid that have shown significant preliminary activity in recurrent and refractory lymphomas. Their future role in front-line management remains to be determined. PMID- 22035757 TI - Management options for follicular lymphoma: observe; R-CHOP; B-R; others? AB - Treatment results are improving for patients who have advanced-stage follicular lymphoma; this progress is in large part related to the inclusion of anti-CD20 monoclonal antibody therapy in front-line therapy programs. Rituximab has been combined successfully in chemo-immunotherapy regimens with several standard chemotherapy combinations, and with bendamustine. Post-remission treatment strategies, including radioimmuotherapy consolidation and rituximab maintenance, have had a favorable impact on duration of remission. Thus, although traditional palliative strategies can still have a role in many situations, such approaches must now be placed in perspective with options that have the potential to achieve durable disease control. Recent therapeutic advances have renewed the hope that potentially curative treatment options may be forthcoming for these patients. PMID- 22035759 TI - Neural coding in graphs of bidirectional associative memories. AB - In the last years we have developed large neural network models for the realization of complex cognitive tasks in a neural network architecture that resembles the network of the cerebral cortex. We have used networks of several cortical modules that contain two populations of neurons (one excitatory, one inhibitory). The excitatory populations in these so-called "cortical networks" are organized as a graph of Bidirectional Associative Memories (BAMs), where edges of the graph correspond to BAMs connecting two neural modules and nodes of the graph correspond to excitatory populations with associative feedback connections (and inhibitory interneurons). The neural code in each of these modules consists essentially of the firing pattern of the excitatory population, where mainly it is the subset of active neurons that codes the contents to be represented. The overall activity can be used to distinguish different properties of the patterns that are represented which we need to distinguish and control when performing complex tasks like language understanding with these cortical networks. The most important pattern properties or situations are: exactly fitting or matching input, incomplete information or partially matching pattern, superposition of several patterns, conflicting information, and new information that is to be learned. We show simple simulations of these situations in one area or module and discuss how to distinguish these situations based on the overall internal activation of the module. This article is part of a Special Issue entitled "Neural Coding". PMID- 22035758 TI - Allogeneic stem cell transplantation for chronic myeloid leukemia resistant to tyrosine kinase inhibitors. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is well-established as a potentially curative treatment for patients who have chronic myeloid leukemia. The success of imatinib and other tyrosine kinase inhibitors (TKI) as initial therapy has changed the treatment paradigm for this disease. Allogeneic hematopoietic transplants are now reserved for patients whose disease does not respond optimally to TKI treatment. Patients whose disease does not have an optimal response to imatinib may respond to a second-generation TKI, dasatinib or nilotinib, and many achieve major or complete molecular and cytogenetic responses. The indication for allogeneic HSCT versus continued second-line therapy is not well-defined and is the subject of ongoing study. There has been continued progress in reducing the toxicity and risks of HSCT with development of reduced-intensity regimens; transplants can be routinely performed in patients up to the age of 75 years who are in fair general medical condition. Transplantation results from unrelated donors have improved, with survival rates similar that achieved with matched siblings. Results with haploidentical and cord blood transplants have markedly improved, and should be considered for patients lacking a matched donor. Allogeneic hematopoietic transplants have the best chance to be curative in patients with chronic phase that is under hematologic control with 80% disease-free survival; patients progressing to the accelerated phase or blast crisis have a much poorer prognosis. Thus, HSCT should be considered for patients with imatinib failure. Patients receiving second-line TKI therapy must be closely monitored and referred for transplantation if a complete cytogenetic response and major molecular response is not achieved. HSCT should be performed if feasible in patients without a continued response to TKI treatment. PMID- 22035760 TI - An investigation of the mode of sorption of inositol hexaphosphate to goethite. AB - Adsorption of inositol hexaphosphate (IP(6)) on goethite has been studied as a function of pH and concentration, and by use of Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR). While adsorption was highest at low pH, a significant amount remained adsorbed above pH 10 where, in the absence of IP(6), the surface is expected to have a net negative charge. The adsorption isotherm at pH 5.5 indicated strong binding to the surface with each adsorbed species occupying about 2.5 nm(2). ATR-FTIR spectra of IP(6) solutions in the pH range from 2 to 12 were fitted with a single set of IR bands which were assigned primarily by analogy with phosphate spectra. From its variation in intensity with pH the band at 1040 cm(-1) was assigned to the effect of hydrogen bonding on the PO vibration. No additional bands were required to fit the spectra of IP(6) adsorbed to goethite, indicating that adsorption occurs by outer-sphere complexation in this system. At all pH values studied the band associated with hydrogen bonding was more intense for the adsorbed species than in solution at the corresponding pH indicating that hydrogen bonding plays an important role in binding IP(6) to goethite. PMID- 22035761 TI - Benefit of immediate revascularization in women with critical limb ischemia in an intention-to-treat analysis. AB - BACKGROUND: Evidence for the best treatment strategy in women with critical limb ischemia (CLI) is limited and controversial with studies contradicting each other. Therefore, we determined the benefit of immediate revascularization compared to medical therapy (MT) with optional delayed revascularization in men and women with CLI. METHODS: This cohort study with follow-up at 2, 6, and 12 months was conducted in a consecutive series of 356 patients (41% women) presenting with 394 critically ischemic limbs. In this intention-to-treat study, 292 limbs were assigned to immediate revascularization by either surgical (81 limbs) or endovascular techniques (211 limbs) at the time of first presentation with CLI, whereas MT as first-line therapy was administered in 102 limbs with CLI. Primary outcome measures were overall and amputation-free survival. Cox regression models adjusted for 10 baseline characteristics following Kaplan-Meier Survival estimates were performed. RESULTS: Women with CLI were significantly older than men (P < .001), had higher systolic blood pressure (P = .03) and cholesterol levels (P = .04), but less women presented with renal failure (P = .03) and less were smokers (P < .001). In women, but not in men, immediate revascularization was associated with a prolonged overall survival (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.29-4.34; P = .01) and amputation-free survival compared to MT (HR, 2.11; 95% CI, 1.30-3.43; P = .01), irrespective of whether surgery or percutaneous transluminal angioplasty (PTA) was performed (not significant). Except for overall survival (HR, 2.14; 95% CI, 0.95-4.82; P = .07), outcomes were not significantly changed after Cox regression analysis. CONCLUSION: Women presenting with CLI profit from immediate revascularization therapy, irrespective of revascularization technique used and despite advanced age and differences in other cardiovascular risk factors. Thus, our data suggest aggressive and early limb salvage efforts in women with CLI. PMID- 22035762 TI - The Nationwide Inpatient Sample may contain inaccurate data for carotid endarterectomy and carotid stenting. AB - The Nationwide Inpatient Sample (NIS) contains information from discharge abstracts submitted by hundreds of community hospitals across the United States, and it frequently has been used as a resource for population-based research comparing the safety of carotid artery stenting (CAS) to that of carotid endarterectomy (CEA). However, at least two findings from the NIS dataset seem open to question. First, several NIS studies have indicated that more than 90% of CEAs and CAS procedures now are being done in asymptomatic patients, a figure that substantially exceeds the prevalence of asymptomatic patients that has been reported elsewhere. Second, these studies also have suggested that the periprocedural stroke rate for CEA and CAS is lower at community hospitals contributing to the NIS than it was in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), even though the surgeons and interventionalists participating in CREST were stringently selected according to their previous experience and results. Neither of these two findings seems to pass the test of face validity. Furthermore, some unexpectedly low stroke-to death (STD) ratios are present in the NIS data, especially for CAS. These issues may be related to poor documentation of preprocedural symptoms and periprocedural strokes in the medical records and to subsequent coding errors in the hospital discharge abstracts on which the NIS is based. PMID- 22035763 TI - Prevalence and metabolic abnormalities of vitamin D-inadequate patients presenting with urolithiasis to a tertiary stone clinic. AB - OBJECTIVE: To assess the prevalence and metabolic abnormalities of patients with inadequate vitamin D (VD) presenting with urolithiasis to a tertiary stone clinic in North America. MATERIAL AND METHODS: A retrospective review of consecutive patients presenting from August 2009 to January 2010 was performed. Demographic and clinical data were collected together with metabolic stone workup, including 2 24-hour urine collections and serum 25-hydroxy VD [25(OH)D]. VD inadequacy (VDI) included VD deficiency and VD insufficiency defined as 25-(OH) VD levels <20 ng/mL and 21-29 ng/mL, respectively. RESULTS: Of 101 patients, 81 (80.2%) were found to have VDI: 34 (33.7%) were deficient and 47 (46.5%) had insufficient VD. Mean age was 50.4 +/- 15.8 years and the mean body mass index was 28.7 +/- 5.8 kg/m(2). Forty-two percent were smokers, 51% were recurrent stone formers, and 54% had positive family history of urolithiasis. Hyperparathyroidism was detected in 25.9% of patients, of which 91% of them were secondary to VDI. Hypocalcemia and hyperuricemia were found in 36% and 11% of patients, respectively. Of 81 VDI patients, 69 (85.2%) had complete 24-hour urine collections, of which 92.7% had at least one abnormality. However, only 40% of patients with normal VD had metabolic abnormalities (P <.0001). The most prevalent pattern of urinary abnormalities in VDI patients were suboptimal volume (45%), hypocitaturia (24%), hypocalciuria (33%), hypercalciuria (20%), hyperuricosuria (16%), cystinuria (5%), and hyperoxaluria (7.2%). CONCLUSION: In this preliminary study, patients presenting with urolithiasis were found to have a high prevalence of inadequate VD associated with abnormalities on metabolic stone work-up. PMID- 22035764 TI - Gleason pattern 5 is frequently underdiagnosed on prostate needle-core biopsy. AB - OBJECTIVE: To assess underdiagnosing Gleason pattern 5 on needle biopsy and discuss the potential consequences for patient management. MATERIAL AND METHODS: We retrieved 300 consecutive prostate biopsy cases from the consultation files at The Johns Hopkins Hospital (JHH) from 2009-2010 in which we identified Gleason pattern 5. All of these cases were diagnosed by one of the authors and all were sent in as a final diagnosis for which the outside pathologist was not requesting consultation because of difficulty with the diagnosis. The Gleason grades assigned to these cases at our institution were compared with the grade rendered by the submitting pathologists from the outside institution. RESULTS: In 146 (48.7%) of the cases, Gleason pattern 5 was not identified by the outside pathologists. Of the 146 cases, the outside Gleason score was <=7 in 61 (20.3%) and 4+4=8 in 85 (28.4%). Even when the tumor was diagnosed at JHH as Gleason score 5+5=10, only 26 (41.3%) were diagnosed as the same by the outside pathologists; Gleason score 9 was graded in 27 (42.8%). CONCLUSION: Considering the important prognostic and therapeutic implication of misdiagnosing Gleason pattern 5, efforts should be made by the pathology community to acknowledge this as a problem and improve on individual pathologists' accuracy by diverse medical education programs. In addition, urologists should not hesitate in sending biopsies with high-grade prostate cancer for expert genitourinary pathology second opinions. PMID- 22035765 TI - Bipolar plasmakinetic transurethral resection of prostate in 132 consecutive patients with large gland: three-year follow-up results. AB - OBJECTIVE: To assess the safety, efficacy, and medium-term durability of bipolar plasmakinetic transurethral resection of the prostate (PK-TURP) for the treatment of bladder outlet obstruction due to benign prostatic hyperplasia in a prospective study. METHODS: From March 2007 to May 2008, 132 consecutive patients underwent PK-TURP at our institution. All patients were assessed perioperatively and followed up at 1, 3, 6, 12, 18, 24, and 36 months postoperatively. The parameters included the International Prostate Symptom Score, quality of life scores, maximal urinary flow rates, transrectal ultrasonography, postvoid residual urine volume, and serum prostate-specific antigen level. RESULTS: The mean patient age was 64.55+/-4.03 years. The prostate volume was 79.66+/-12.36 g. The operative time was 78.83+/-17.41 minutes, and the resected weight was 58.12+/ 7.29 g. The catheterization time was 69.00+/-17.99 hours, and the hospital stay was 117.00+/-17.99 hours. The decrease in hemoglobin and sodium was 1.55+/-0.48 g/dL and 1.57+/-0.38 mmol/L, respectively. A significant improvement occurred in the maximal urinary flow rate (22.34+/-3.1 mL/s), International Prostate Symptom Score (2.90+/-1.60), and quality of life (1.12+/-0.60) at the 3-year follow-up compared with baseline (P<.001). Of the 132 patients, 6 (4.5%) required reoperation. CONCLUSION: PK-TURP represents an effective surgical intervention for the treatment of bladder outlet obstruction for large prostates. Furthermore, the functional results at 3 years demonstrated durability. Therefore, the PK-TURP technique could play an important role in the surgical treatment of patients with symptomatic benign prostatic hyperplasia with a large prostate gland. PMID- 22035766 TI - The developmental quality of participation experiences: beyond the rhetoric that "participation is always good!". AB - A powerful rhetoric regarding the importance of adolescents' civic engagement and political participation is common in contemporary societies, whilst citizens, both adolescent and adults, seem to express a growing scepticism and alienation regarding politics. Even if this disengagement is debatable, as there are simultaneous signs of an increasing involvement in a variety of emerging and broadly-defined civic and political activities, we argue that the benefits of these experiences should be scrutinized using psychological evidence-based criteria. We rest on classical contributions from developmental psychology, educational theory and political science to define criteria that could inform the quality of participation experiences, and then present two studies that explore its adequacy. Study 1 is a cross-sectional study that observes that higher quality civic and political experiences are connected with more complex modes of thinking about politics. In Study 2, a two-wave longitudinal design, the quality of participation experiences is a significant predictor of change patterns of political attitudes; moreover, results support the argument that participation is not good in itself and that some experiences, with lesser developmental quality, might have a detrimental effect on adolescents' political development. PMID- 22035767 TI - [Agreement between two observers in the measurement of smoking and use of safety belt and cell phones in vehicles]. AB - The aim of this study was to assess the feasibility of direct observations of smoking and use of seat belts and cell phones in drivers in the city of Barcelona, and to analyze the agreement between two observers. We performed 315 pairs of observations. The simple percentage inter-observer agreement between driver and passenger smoking was 100% with a Kappa coefficient=1.0. There was high inter-observer agreement in measurement of cell phone use and the number of passengers aged less than 14 years old. The variable with the lowest agreement was the driver's age. In conclusion, direct observation studies are a good resource for monitoring smoking and use of seat belts and cell phones in the drivers of motor vehicles. PMID- 22035768 TI - Effects of ethanolic extract from Radix Scrophulariae on ventricular remodeling in rats. AB - PURPOSE: To explore the effects of ethanolic extract of Radix Scrophulariae (EERS) on ventricular remodeling in rats. METHODS: Rats with coronary artery ligation (CAL) were randomly assigned to 5 groups: CAL model; CAL plus 40 mg/kg captopril; CAL plus 60 mg/kg, 120 mg/kg, 240 mg/kg EERS. Sham operation rats were randomly assigned to 2 groups, sham-operated control and sham-operated plus 120 mg/kg EERS. The rats were orally administered with the corresponding drugs or drinking water for 14 weeks. The left ventricular weight index (LVWI) and heart weight index (HWI) were determined. Myocardium tissue was stained with hematoxylin and eosin or picric acid/Sirius red for cardiomyocyte cross-section area or collagen content measurements respectively. The concentrations of hydroxyproline (Hyp), matrix metalloproteinase 2 (MMP-2), angiotensin II (Ang II), aldosterone (ALD), endothelin 1 (ET-1), atrial natriuretic peptide (ANP), tumor necrosis factor alpha (TNF-alpha) and renin activity (RA) in myocardium or serum were determined. Real-time RT-PCR was used to detect the mRNA expressions of angiotensin converting enzyme (ACE), ET-1 and ANP. RESULTS: EERS could significantly reduce the LVWI and HWI, decrease heart tissue concentrations of Hyp and collagen deposition, diminish cardiomyocyte cross-section area, reduce the tissue level of Ang II, ET-1, ANP and TNF-alpha. EERS could also down regulate the mRNA expression of ACE, ET-1 and ANP in myocardium. CONCLUSION: EERS attenuates ventricular remodeling. The mechanisms may be related to restraining the excessive activation of RAAS, TNF-alpha and modulating some gene expressions associated with cardiac hypertrophy. PMID- 22035769 TI - Tanshinone IIA and tanshinone I production by Trichoderma atroviride D16, an endophytic fungus in Salvia miltiorrhiza. AB - In this study the isolation of an endophytic fungus from the root of the medicinal herb Salvia miltiorrhiza Bunge is reported for the first time. The fungus produced tanshinone I and tanshinone IIA in rich mycological medium (potato dextrose broth) under shake flask and bench scale fermentation conditions. The fungus was identified as Trichoderma atroviride by its morphology and authenticated by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S rDNA region). Tanshinone I and tanshinone IIA were identified by HPLC and LC HRMS/MS and confirmed through comparison with authentic standards. This endophytic fungus has significant scientific and industrial potential to meet the pharmaceutical demands for tanshinone I and tanshinone IIA in a cost-effective, easily accessible and reproducible way. PMID- 22035770 TI - The real mystery about language. Comment on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22035771 TI - Where could biolinguists and evolutionary linguists meet? Comment on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22035772 TI - Emotional voices in context: a neurobiological model of multimodal affective information processing. AB - Just as eyes are often considered a gateway to the soul, the human voice offers a window through which we gain access to our fellow human beings' minds - their attitudes, intentions and feelings. Whether in talking or singing, crying or laughing, sighing or screaming, the sheer sound of a voice communicates a wealth of information that, in turn, may serve the observant listener as valuable guidepost in social interaction. But how do human beings extract information from the tone of a voice? In an attempt to answer this question, the present article reviews empirical evidence detailing the cerebral processes that underlie our ability to decode emotional information from vocal signals. The review will focus primarily on two prominent classes of vocal emotion cues: laughter and speech prosody (i.e. the tone of voice while speaking). Following a brief introduction, behavioral as well as neuroimaging data will be summarized that allows to outline cerebral mechanisms associated with the decoding of emotional voice cues, as well as the influence of various context variables (e.g. co-occurring facial and verbal emotional signals, attention focus, person-specific parameters such as gender and personality) on the respective processes. Building on the presented evidence, a cerebral network model will be introduced that proposes a differential contribution of various cortical and subcortical brain structures to the processing of emotional voice signals both in isolation and in context of accompanying (facial and verbal) emotional cues. PMID- 22035773 TI - The cultural approach to language is ripe, let us expand our options to test it empirically. Commentary on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22035774 TI - Control chart pattern recognition using K-MICA clustering and neural networks. AB - Automatic recognition of abnormal patterns in control charts has seen increasing demands nowadays in manufacturing processes. This paper presents a novel hybrid intelligent method (HIM) for recognition of the common types of control chart pattern (CCP). The proposed method includes two main modules: a clustering module and a classifier module. In the clustering module, the input data is first clustered by a new technique. This technique is a suitable combination of the modified imperialist competitive algorithm (MICA) and the K-means algorithm. Then the Euclidean distance of each pattern is computed from the determined clusters. The classifier module determines the membership of the patterns using the computed distance. In this module, several neural networks, such as the multilayer perceptron, probabilistic neural networks, and the radial basis function neural networks, are investigated. Using the experimental study, we choose the best classifier in order to recognize the CCPs. Simulation results show that a high recognition accuracy, about 99.65%, is achieved. PMID- 22035775 TI - A novel KFCM based fault diagnosis method for unknown faults in satellite reaction wheels. AB - Reaction wheels are one of the most critical components of the satellite attitude control system, therefore correct diagnosis of their faults is quintessential for efficient operation of these spacecraft. The known faults in any of the subsystems are often diagnosed by supervised learning algorithms, however, this method fails to work correctly when a new or unknown fault occurs. In such cases an unsupervised learning algorithm becomes essential for obtaining the correct diagnosis. Kernel Fuzzy C-Means (KFCM) is one of the unsupervised algorithms, although it has its own limitations; however in this paper a novel method has been proposed for conditioning of KFCM method (C-KFCM) so that it can be effectively used for fault diagnosis of both known and unknown faults as in satellite reaction wheels. The C-KFCM approach involves determination of exact class centers from the data of known faults, in this way discrete number of fault classes are determined at the start. Similarity parameters are derived and determined for each of the fault data point. Thereafter depending on the similarity threshold each data point is issued with a class label. The high similarity points fall into one of the 'known-fault' classes while the low similarity points are labeled as 'unknown-faults'. Simulation results show that as compared to the supervised algorithm such as neural network, the C-KFCM method can effectively cluster historical fault data (as in reaction wheels) and diagnose the faults to an accuracy of more than 91%. PMID- 22035776 TI - Mixture of fibroblast, epithelial and endothelial cells conditioned media induce monocyte-derived dendritic cell maturation. AB - Fully matured DCs with large amount cytoplasm and copious dendritic projections were visible at the end of culturing period in the presence of MCM, TNF-alpha and poly (I:C), with or without FEECM. Thus, DCs generated with these maturation factors are nonadherent and have typical satellite morphology. Flow cytometric analysis using anti-CD14, -CD80, -CD86, -HLA-DR and -CD83 revealed that expression of CD14 is decreased in particular in FEECM treated DCs, on day 5 and expression of CD80, CD86 and HLA-DR was the higher when FEECM are added to maturation factor. Functionally, when DCs matured in the presence of FEECM elicited stronger MLR, reduced phagocytic activity. These results support the use of the FEECM with MCM, TNF-alpha and poly (I-C) as maturation factor in DC generation that could result in functionally mature monocyte-derived DCs in comparison to either alone. PMID- 22035777 TI - Excellent outcomes with use of synthetic vascular grafts for treatment of mycotic aortic pseudoaneurysms after heart transplantation. AB - BACKGROUND: Mycotic pseudoaneurysm is a rare but potentially lethal complication after heart transplantation. Allograft has been advocated as the choice of material for aortic replacement. We report a series of 7 patients with pseudoaneurysm that was treated with primary repair or synthetic graft replacement. METHODS: Between October 2005 and February 2011, 8 patients (mean age, 55.3 years; range, 39 to 67 years), were diagnosed with mycotic pseudoaneurysms of the ascending aorta 2 to 29 months after transplantation. One patient declined operative repair, and the remainder had urgent or emergency surgical intervention. One patient had primary repair at the cardioplegia site, and one had primary end-to-end anastomosis after the infected recipient aortic segment was resected. Five patients had replacement of the infected aorta with a Dacron graft (DuPont, Wilmington, DE) for pseudoaneurysm development at the suture line or donor aorta. Clinical and radiologic follow-up assessments were performed in all patients. RESULTS: There were no operative or in-hospital deaths. None of the patients had major postoperative complications, and there was no cardiac allograft dysfunction. Median follow-up was 25 months (range, 1 to 48 months). One patient died of a pulmonary embolism 10 months after the operation. The remaining 6 patients remain free of infection. The most recent radiologic follow-up showed no residual or recurrence of pseudoaneurysms among the surviving patients. CONCLUSIONS: A synthetic vascular graft to replace the infected aorta is a viable aortic substitute among transplant recipients, and in the presence of a vascularized flap, can offer excellent midterm outcomes. PMID- 22035778 TI - Mechanisms of pulmonary hypertension related to ventricular septal defect in congenital heart disease. AB - BACKGROUND: The aim of this study was to investigate differences in molecular mechanisms of pulmonary hypertension between patients with complete transposition of the great arteries (TGA) combined with ventricular septal defect (VSD) and those with VSD alone. METHODS: Twenty-four consecutive patients with pulmonary hypertension (mean pulmonary artery pressure > 30 mm Hg) underwent surgical correction of TGA + VSD (n = 10) or VSD alone (n = 14). Lung specimens were taken from the right middle lobe before cardiopulmonary bypass (CPB). Extent of pulmonary hypertension was graded according to the Heath-Edwards pathologic classification. Enzyme-linked immunosorbent assay (ELISA) was used to determine expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), endothelin-1 (ET-1), endothelin A and B receptors (ET-AR, ET BR), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), and tissue inhibitor of metalloproteinase (TIMP). RESULTS: There were no statistically significant differences in age, height, weight, VSD diameter, or preoperative pulmonary artery pressure between groups. Hemoglobin level, pulmonary artery oxygen saturation, and reduction in postoperative pulmonary artery pressure were significantly higher in patients undergoing correction of TGA + VSD (p < 0.05). All patients had grade 0 to II Heath-Edwards morphologic changes in lung biopsy samples. Expression of eNOS and MMP-2 was significantly lower in the TGA + VSD group than in the VSD-alone group (eNOS, 280.13 +/- 101.92 ng/mg versus 488.41 +/ 249.60 ng/mg; p < 0.05; MMP-2, 31.68 +/- 15.36 ng/mg versus 69.28 +/- 49.12 ng/mg; p < 0.05). There were no statistically significant differences between groups in expression of iNOS, ET-1, ET-AR, ET-BR, MMP-9, or TIMP. CONCLUSIONS: In patients with TGA + VSD, high oxygenation in the pulmonary circulation decreases expression of MMP-2 and eNOS, which may affect the progress and reversibility of pulmonary hypertension. PMID- 22035779 TI - Soluble ST2 is a marker for acute cardiac allograft rejection. AB - BACKGROUND: Soluble ST2 (sST2), an interleukin (IL)-1 receptor family member, has a role in immunologic tolerance and has also emerged as a biomarker of cardiac stretch and remodeling. The sST2 role in heart transplantation is still unknown. METHODS: From the heart transplantation population at our institution (n = 74), we selected a subset of 26 patients who had an acute rejection episode in the first year after transplantation (35%; 52 +/- 14 years; 76% men). Endomyocardial biopsy (EMB) results obtained at the time of the first rejection episode represented the rejection cohort (n = 26). Each patient served as a control to himself or herself, with EMB without rejection obtained before and after the rejection episode (n = 52). All laboratory measurements and blood samples were obtained at the time of EMB. RESULTS: sST2 concentrations rose significantly in the context of acute rejection (130 [60 to 238] versus 51 ng/mL [28 to 80]; p = 0.002). Tertile analyses of sST2 concentrations revealed a graded association with rejection (p = 0.002) and repeated measurement analyses showed that sST2 concentrations were significantly modulated by the presence of rejection (p = 0.001). In receiver operator characteristic (ROC) analysis, sST2 had an area under the curve (AUC) of 0.72; the optimal cutoff point was 68 ng/mL (positive predictive value of 53%, negative predictive value of 83%), which predicted acute cellular rejection (odds ratio [OR] 4.9; 95% confidence interval [CI], 1.7 to 14.5; p = 0.004). The addition of sST2 values to those for the N-terminal pro B type natriuretic peptide (NT-proBNP) resulted in a significant improvement on the integrated discrimination index (IDI) for rejection (relative improvement of 24%; p = 0.021). CONCLUSIONS: sST2 concentrations are modulated by the presence of acute rejection and provide complementary predictive ability to NT-proBNP for the biochemical identification of rejection. PMID- 22035780 TI - Diagnostic knee arthroscopy: a pilot study to evaluate surgical skills. AB - PURPOSE: To develop a scoring system to evaluate individual proficiency at diagnostic knee arthroscopy. METHODS: This was a prospective blinded study. Subjects included residents in postgraduate year (PGY) 1 through PGY 5 (n = 20) and staff surgeons (n = 10). All subjects performed a diagnostic arthroscopy on a cadaveric knee. Subjects were evaluated on both completeness and time required to complete the arthroscopy. The examiner viewed the arthroscopy from a remote location and was blinded to the level of training of the subjects. During the arthroscopy, 15 areas required assessment to achieve a score of 75 points. An additional 25 points were awarded depending on the time it took to complete the arthroscopy. A maximum of 100 points were available (Total score = Arthroscopy score + Time score). RESULTS: Thirty subjects were divided into 3 groups: group 1 (PGY 1 or 2) (n = 12), group 2 (PGY 3, 4, or 5) (n = 8), and group 3 (staff) (n = 10). In group 1 the mean total score was 28.25 points, the mean time to complete arthroscopy was 11.9 minutes, and the mean number of structures not examined was 8.67. In group 2 the mean total score was 76 points, the mean time to complete arthroscopy was 8.2 minutes, and the mean number of structures not examined was 1.75. In group 3 the mean total score was 100 points, the mean time to complete arthroscopy was 4.6 minutes, and the mean number of structures not examined was 0. Statistically significant differences by use of an analysis of variance test were noted for the total score, total time, and number of missed structures (P < .001). CONCLUSIONS: Using our skills assessment tool, we were able to evaluate subjects and determine their relative technical skill level in performing a diagnostic arthroscopy. This tool was able to distinguish among the novice, experienced, and expert levels in performing diagnostic arthroscopy. LEVEL OF EVIDENCE: Level III, development of diagnostic criteria on the basis of consecutive subjects. PMID- 22035781 TI - Optimizing pressurized contact area in rotator cuff repair: the diamondback repair. AB - PURPOSE: The purpose of this study was to compare tendon-bone footprint contact area over time under physiologic loads for 4 different rotator cuff repair techniques: single row (SR), triangle double row (DR), chain-link double row (CL), and diamondback double row (DBK). METHODS: A supraspinatus tear was created in 28 human cadavers. Tears were fixed with 1 of 4 constructs: SR, DR, CL, or DBK. Immediate post-repair measurements of pressurized contact area were taken in neutral rotation and 0 degrees of abduction. After a static tensile load, pressurized contact area was observed over a 160-minute period after repair. Cyclic loading was then performed. RESULTS: The DBK repair had the highest pressurized contact area initially, as well as the highest pressurized contact area and lowest percentage decrease in pressurized contact area after 160 minutes of testing. The DBK repair had significantly larger initial pressurized contact than CL (P = .003) and SR (P = .004) but not DR (P = .06). The DBK technique was the only technique that produced a pressurized contact area that exceeded the native footprint both at initial repair (P = .01) and after 160 minutes of testing (P = .01). DBK had a significantly larger mean pressurized contact area than all the repairs after 160 minutes of testing (P = .01). DBK had a significantly larger post-cyclic loading pressurized contact area than CL (P = .01) and SR (P = .004) but not DR (P = .07). CONCLUSIONS: This study showed that a diamondback repair (a modification of the transosseous repair) can significantly increase the rotator cuff pressurized contact area in comparison with other standard rotator cuff repair constructs when there is sufficient tendon mobility to perform a double-row repair without excessive tension on the repair site. CLINICAL RELEVANCE: The persistent pressurized contact area of a DBK repair may be desirable to enhance healing potential when there is sufficient tendon mobility to perform a double-row repair, particularly for large or massive rotator cuff tears where it is important to optimize footprint area and contact to encourage biologic healing. PMID- 22035783 TI - Future fuel: could biomass be the new petroleum? PMID- 22035782 TI - Transcriptomic analysis of pluripotent stem cells: insights into health and disease. AB - Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold tremendous clinical potential because of their ability to self-renew, and to differentiate into all cell types of the body. This unique capacity of ESCs and iPSCs to form all cell lineages is termed pluripotency. While ESCs and iPSCs are pluripotent and remarkably similar in appearance, whether iPSCs truly resemble ESCs at the molecular level is still being debated. Further research is therefore needed to resolve this issue before iPSCs may be safely applied in humans for cell therapy or regenerative medicine. Nevertheless, the use of iPSCs as an in vitro human genetic disease model has been useful in studying the molecular pathology of complex genetic diseases, as well as facilitating genetic or drug screens. Here, we review recent progress in transcriptomic approaches in the study of ESCs and iPSCs, and discuss how deregulation of these pathways may be involved in the development of disease. Finally, we address the importance of these advances for developing new therapeutics, and the future challenges facing the clinical application of ESCs and iPSCs. PMID- 22035784 TI - L-DOPA ropes in tRNA(Phe). AB - L-DOPA is the most commonly prescribed drug for the treatment of Parkinson's disease. Here, Moor et al. (2011) report that phenylalanyl-tRNA synthetase catalyzes the misacylation of tRNA(Phe) by L-DOPA, suggesting that it may contribute to the elevated levels of L-DOPA-containing proteins found in patients treated with this drug. PMID- 22035785 TI - Green-red flashers to accelerate biology. AB - Photoactivatable fluorescent proteins are now widely used for cell and protein tracking and super-resolution optical imaging. In this issue, Adam et al. (2011) report a general approach to introduce photochromism into green-to-red photoconvertible proteins and describe new photoactivatable protein with a complex four-state flasher-like behavior and advanced characteristics. PMID- 22035786 TI - Biology-driven library design for probe discovery. AB - Libraries of diverse small molecules are important to probe and drug discovery. The current trend toward building massive screening collections to support drug development, a special application of chemical biology, can limit their broader potential. Biology-driven construction methods (Wallace et al., 2011) are rapidly emerging to bring chemical libraries back on a viable path. PMID- 22035787 TI - Tailor-made peptide synthetases. AB - Harnessing the modular architecture of non-ribosomal peptide synthetases for combinatorial biosynthesis is a longstanding goal in chemical biology. Several recent reports illustrate how computational design and directed evolution can be used to tailor the specificity of these assembly-line enzymes. PMID- 22035788 TI - Aspirin-triggered metabolites of EFAs. AB - Aspirin triggers the biosynthesis of oxygenated metabolites from arachidonic, eicosapentaenoic, and docosahexaenoic (DHA) acids. In a preceding issue, Serhan et al. (2011) describe a novel aspirin-triggered DHA pathway for the biosynthesis of a potent anti-inflammatory and proresolving molecule. PMID- 22035789 TI - PNA to DNA to microarray decoding facilitates ligand discovery. AB - The development of a method for the amplification of PNA tags (Svensen et al., in this issue of Chemistry & Biology) should expand the range of biological targets amenable to screening using PNA-encoded combinatorial libraries and thus facilitate the discovery of new biologically useful agents. PMID- 22035790 TI - Generation, translocation, and action of nitric oxide in living systems. AB - Nitric oxide (NO) is a gaseous diatomic radical that is involved in a wide range of physiological and pathological functions in biology. Conceptually, the biochemistry of NO can be separated into three stages: generation (stage 1), translocation (stage 2), and action (stage 3). In stage 1 the oxygenase domain of NO synthase converts L-arginine to L-citrulline and NO (g). Owing to its short lived nature, this molecule is converted into a different nitrogen oxide such as NO(2), an organonitrosyl such as a nitrosothiol, or a metal nitrosyl such as a heme-nitrosyl, for transportation in stage 2. Each of these derivatives features unique physical characteristics, chemical reactivity, and biological activity. Upon delivery in stage 3, NO exerts its physiological or pathological function by reaction with biomolecules containing redox-active metals or other residues. PMID- 22035791 TI - Bacterial and eukaryotic phenylalanyl-tRNA synthetases catalyze misaminoacylation of tRNA(Phe) with 3,4-dihydroxy-L-phenylalanine. AB - Aminoacyl-tRNA synthetases exert control over the accuracy of translation by selective pairing the correct amino acids with their cognate tRNAs, and proofreading the misacylated products. Here we show that three existing, structurally different phenylalanyl-tRNA synthetases-human mitochondrial (HsmtPheRS), human cytoplasmic (HsctPheRS), and eubacterial from Thermus thermophilus (TtPheRS), catalyze mischarging of tRNA(Phe) with an oxidized analog of tyrosine-L-dopa. The lowest level of L-dopa discrimination over the cognate amino acid, exhibited by HsmtPheRS, is comparable to that of tyrosyl-tRNA synthetase. HsmtPheRS and TtPheRS complexes with L-dopa revealed in the active sites an electron density shaping this ligand. HsctPheRS and TtPheRS possessing editing activity are capable of hydrolyzing the exogenous L-dopa-tRNA(Phe) as efficiently as Tyr-tRNA(Phe). However, editing activity of PheRS does not guarantee reduction of the aminoacylation error rate to escape misincorporation of L-dopa into polypeptide chains. PMID- 22035793 TI - Rational design of photoconvertible and biphotochromic fluorescent proteins for advanced microscopy applications. AB - Advanced fluorescence imaging, including subdiffraction microscopy, relies on fluorophores with controllable emission properties. Chief among these fluorophores are the photoactivatable fluorescent proteins capable of reversible on/off photoswitching or irreversible green-to-red photoconversion. IrisFP was recently reported as the first fluorescent protein combining these two types of phototransformations. The introduction of this protein resulted in new applications such as super-resolution pulse-chase imaging. However, the spectroscopic properties of IrisFP are far from being optimal and its tetrameric organization complicates its use as a fusion tag. Here, we demonstrate how four state optical highlighting can be rationally introduced into photoconvertible fluorescent proteins and develop and characterize a new set of such enhanced optical highlighters derived from mEosFP and Dendra2. We present in particular NijiFP, a promising new fluorescent protein with photoconvertible and biphotochromic properties that make it ideal for advanced fluorescence-based imaging applications. PMID- 22035792 TI - Structural and mechanistic insights into C-P bond hydrolysis by phosphonoacetate hydrolase. AB - Bacteria have evolved pathways to metabolize phosphonates as a nutrient source for phosphorus. In Sinorhizobium meliloti 1021, 2-aminoethylphosphonate is catabolized to phosphonoacetate, which is converted to acetate and inorganic phosphate by phosphonoacetate hydrolase (PhnA). Here we present detailed biochemical and structural characterization of PhnA that provides insights into the mechanism of C-P bond cleavage. The 1.35 A resolution crystal structure reveals a catalytic core similar to those of alkaline phosphatases and nucleotide pyrophosphatases but with notable differences, such as a longer metal-metal distance. Detailed structure-guided analysis of active site residues and four additional cocrystal structures with phosphonoacetate substrate, acetate, phosphonoformate inhibitor, and a covalently bound transition state mimic provide insight into active site features that may facilitate cleavage of the C-P bond. These studies expand upon the array of reactions that can be catalyzed by enzymes of the alkaline phosphatase superfamily. PMID- 22035794 TI - Identification of a eukaryotic reductive dechlorinase and characterization of its mechanism of action on its natural substrate. AB - Chlorinated compounds are important environmental pollutants whose biodegradation may be limited by inefficient dechlorinating enzymes. Dictyostelium amoebae produce a chlorinated alkyl phenone called DIF which induces stalk cell differentiation during their multicellular development. Here we describe the identification of DIF dechlorinase. DIF dechlorinase is active when expressed in bacteria, and activity is lost from Dictyostelium cells when its gene, drcA, is knocked out. It has a K(m) for DIF of 88 nM and K(cat) of 6.7 s(-1). DrcA is related to glutathione S-transferases, but with a key asparagine-to-cysteine substitution in the catalytic pocket. When this change is reversed, the enzyme reverts to a glutathione S-transferase, thus suggesting a catalytic mechanism. DrcA offers new possibilities for the rational design of bioremediation strategies. PMID- 22035795 TI - Rational development of caged-biotin protein-labeling agents and some applications in live cells. AB - Biotin-(strept)avidin complex is widely used in biotechnology because of its extremely high binding constant, but there is no report describing spatiotemporally controlled formation of the complex in live cells. Here, based on X-ray crystal structure analysis and calorimetric data, we designed and synthesized photoreleasable biotins, which show greatly reduced affinity for (strept)avidin, but recover native affinity after UV irradiation. For application at the cell surface, we introduced an amine-reactive moiety into these "caged" biotin molecules. Specific fluorescence imaging of live cells that had been labeled with these agents and then UV-irradiated, was accomplished by addition of streptavidin conjugated with a fluorophore. We also demonstrated the applicability of these compounds for UV-irradiated-cell-specific drug delivery by using caged-biotin-labeled cells, a prodrug, and streptavidin conjugated with a prodrug-activating enzyme. PMID- 22035797 TI - Decoding a PNA encoded peptide library by PCR: the discovery of new cell surface receptor ligands. AB - The ability to screen and identify new ligands for cell surface receptors has been a long-standing goal as it might allow targeting of pharmaceutically relevant receptors, such as integrins or G protein coupled receptors. Here, we present a method to amplify hits from a library of PNA-tagged peptides. To this end, human cells, overexpressing either integrins or the CCR6 receptor, were treated with a 10,000 member PNA-encoded peptide library. Extraction of the PNA tags from the surface of the cells was followed by a PNA-tag to DNA translation and amplification enabling decoding of the tags via microarray hybridization. This approach to ligand discovery facilitates screening for differences in surface-receptor ligands and/or receptor expression between different cell types, and opens up a practical approach to PNA-tag amplification. PMID- 22035796 TI - Compound prioritization methods increase rates of chemical probe discovery in model organisms. AB - Preselection of compounds that are more likely to induce a phenotype can increase the efficiency and reduce the costs for model organism screening. To identify such molecules, we screened ~81,000 compounds in Saccharomyces cerevisiae and identified ~7500 that inhibit cell growth. Screening these growth-inhibitory molecules across a diverse panel of model organisms resulted in an increased phenotypic hit-rate. These data were used to build a model to predict compounds that inhibit yeast growth. Empirical and in silico application of the model enriched the discovery of bioactive compounds in diverse model organisms. To demonstrate the potential of these molecules as lead chemical probes, we used chemogenomic profiling in yeast and identified specific inhibitors of lanosterol synthase and of stearoyl-CoA 9-desaturase. As community resources, the ~7500 growth-inhibitory molecules have been made commercially available and the computational model and filter used are provided. PMID- 22035798 TI - Directed evolution of a gatekeeper domain in nonribosomal peptide synthesis. AB - Modular natural products are biosynthesized by series of enzymes that activate, assemble, and process a nascent chain of building blocks. Adenylation domains are gatekeepers in nonribosomal peptide biosynthesis, providing the entry point for assembly of typical peptide-based natural products. We report the directed evolution of an adenylation domain based on a strategy of using a weak, promiscuous activity as a springboard for reprogramming the biosynthetic assembly line. Randomization of residues invoked in a "specificity-conferring code" and selection for a non-native substrate lead to mutant G2.1, favoring smaller amino acids with a specificity change of 10(5): a 170-fold improvement for L-alanine corresponds to a 10(3)-fold decrease for its original substrate (L phenylalanine). These results establish directed evolution as a method to change gatekeeper domain specificity and suggest that adaptation of modules in combinatorial biosynthesis is achievable with few mutations during evolution. PMID- 22035799 TI - Disruption of Wnt planar cell polarity signaling by aberrant accumulation of the MetAP-2 substrate Rab37. AB - Identification of methionine aminopeptidase-2 (MetAP-2) as the molecular target of the antiangiogenic compound TNP-470 has sparked interest in N-terminal Met excision's (NME) role in endothelial cell biology. In this regard, we recently demonstrated that MetAP-2 inhibition suppresses Wnt planar cell polarity (PCP) signaling and that endothelial cells depend on this pathway for normal function. Despite this advance, the substrate(s) whose activity is altered upon MetAP-2 inhibition, resulting in loss of Wnt PCP signaling, is not known. Here we identify the small G protein Rab37 as a MetAP-2-specific substrate that accumulates in the presence of TNP-470. A functional role for aberrant Rab37 accumulation in TNP-470's mode of action is demonstrated using a Rab37 point mutant that is resistant to NME, because expression of this mutant phenocopies the effects of MetAP-2 inhibition on Wnt PCP signaling-dependent processes. PMID- 22035802 TI - Employing modular polyketide synthase ketoreductases as biocatalysts in the preparative chemoenzymatic syntheses of diketide chiral building blocks. AB - Chiral building blocks are valuable intermediates in the syntheses of natural products and pharmaceuticals. A scalable chemoenzymatic route to chiral diketides has been developed that includes the general synthesis of alpha-substituted, beta ketoacyl N-acetylcysteamine thioesters followed by a biocatalytic cycle in which a glucose-fueled NADPH-regeneration system drives reductions catalyzed by isolated modular polyketide synthase (PKS) ketoreductases (KRs). To identify KRs that operate as active, stereospecific biocatalysts, 11 isolated KRs were incubated with 5 diketides and their products were analyzed by chiral chromatography. KRs that naturally reduce small polyketide intermediates were the most active and stereospecific toward the panel of diketides. Several biocatalytic reactions were scaled up to yield more than 100 mg of product. These syntheses demonstrate the ability of PKS enzymes to economically and greenly generate diverse chiral building blocks on a preparative scale. PMID- 22035800 TI - Metabolically stabilized derivatives of phosphatidylinositol 4-phosphate: synthesis and applications. AB - Phosphatidylinositol 4-phosphate (PtdIns(4)P) lipid is an essential component of eukaryotic membranes and a marker of the Golgi complex. Here, we developed metabolically stabilized (ms) analogs of PtdIns(4)P and the inositol 1,4 bisphosphate (IP(2)) head group derivative and demonstrated that these compounds can substitute the natural lipid fully retaining its physiological activities. The methylenephosphonate (MP) and phosphorothioate (PT) analogs of PtdIns(4)P and the aminohexyl (AH)-IP(2) probe are recognized by the PtdIns(4)P-specific PH domain of four phosphate adaptor protein 1 (FAPP1). Binding of FAPP1 to the PtdIns(4)P derivatives stimulates insertion of the PH domain into the lipid layers and induces tubulation of membranes. Both ms analogs and IP(2) probes could be invaluable for identifying protein effectors and characterizing PtdIns(4)P-dependent signaling cascades within the trans-Golgi network (TGN). PMID- 22035801 TI - Promysalin, a salicylate-containing Pseudomonas putida antibiotic, promotes surface colonization and selectively targets other Pseudomonas. AB - Under control of the Gac regulatory system, Pseudomonas putida RW10S1 produces promysalin to promote its own swarming and biofilm formation, and to selectively inhibit many other pseudomonads, including the opportunistic pathogen Pseudomonas aeruginosa. This amphipathic antibiotic is composed of salicylic acid and 2,8 dihydroxymyristamide bridged by a unique 2-pyrroline-5-carboxyl moiety. In addition to enzymes for salicylic acid synthesis and activation, the biosynthetic gene cluster encodes divergent type II fatty acid biosynthesis components, unusual fatty acid-tailoring enzymes (two Rieske-type oxygenases and an amidotransferase), an enzyme resembling a proline-loading module of nonribosomal peptide synthetases, and the first prokaryotic member of the BAHD family of plant acyltransferases. Identification of biosynthetic intermediates enabled to propose a pathway for synthesis of this bacterial colonization factor. PMID- 22035803 TI - [Travel-related dermatosis, returning from tropical regions]. PMID- 22035804 TI - [Travel-related fever]. PMID- 22035805 TI - Treatment of Na(v)1.7-mediated pain in inherited erythromelalgia using a novel sodium channel blocker. AB - Mutations in the SCN9A gene leading to deficiency of its protein product, Na(v)1.7, cause congenital indifference to pain (CIP). CIP is characterized by the absence of the ability to sense pain associated with noxious stimuli. In contrast, the opposite phenotype to CIP, inherited erythromelalgia (IEM), is a disorder of spontaneous pain caused by missense mutations resulting in gain-of function in Na(v)1.7 that promote neuronal hyperexcitability. The primary aim of this study was to demonstrate that Na(v)1.7 antagonism could alleviate the pain of IEM, thereby demonstrating the utility of this opposite phenotype model as a tool for rapid proof-of-concept for novel analgesics. An exploratory, randomized, double-blind, 2-period crossover study was conducted in 4 SCN9A mutation-proven IEM patients. In each treatment period (2days), separated by a 2-day washout period, patients were orally administered XEN402 (400mg twice daily) or matching placebo. In 3 patients, pain was induced by heat or exercise during each treatment arm. A fourth patient, in constant severe pain, required no induction. Patient-reported outcomes of pain intensity and/or relief were recorded, and the time taken to induce pain was measured. The ability to induce pain in IEM patients was significantly attenuated by XEN402 compared with placebo. XEN402 increased the time to maximal pain induction and significantly reduced the amount of pain (42% less) after induction (P=.014). This pilot study showed that XEN402 blocks Na(v)1.7-mediated pain associated with IEM, thereby demonstrating target engagement in humans and underscoring the use of rare genetic disorders with mutant target channels as a novel approach to rapid proof-of-concept. PMID- 22035808 TI - Fertility sparing surgery for treatment of early-stage cervical cancer: open vs. robotic radical trachelectomy. AB - OBJECTIVE: To compare the open versus robotic surgical approaches and provide surgical outcome data on patients who have undergone radical trachelectomy (RT). METHODS: We identified patients who underwent open (ORT) or robotic radical trachelectomy (RRT) between September 2005 and June 2011. Tumor characteristics, perioperative, operative and obstetrical outcomes were analyzed. RESULTS: Thirty seven patients with early stage cervical cancer that desired future fertility underwent attempted radical trachelectomy, and 32 patients (20 with 1B1, 11 with 1A2, and 5 with 1A1 with LVSI/poorly differentiated histology) had successful completion of RT. Five (1 open/4 robotic) underwent conversion to radical hysterectomy secondary to close (<5mm) endocervical margin (p=0.08). The median age at diagnosis was 28.9 years (range; 21.4-37.2), 70% were nulliparous, and 9 had a visible lesion. Twenty-five patients (68%) underwent ORT and 12 (32%) underwent RRT. RRT was associated with less blood loss (62.5 mL vs. 300 mL, p=0.0001) and decreased length of postoperative stay (1 vs. 4 days, p<0.001), with no difference in operative time or histopathologic outcomes. Twenty-three patients (62%) had no residual cervical disease on final pathology. Common long term morbidities were irregular menstrual bleeding or amenorrhea (25%), cerclage erosion (13%), or cervical stenosis (9%). Although there was a higher rate of conversion to hysterectomy in the robotic surgery cohort, rates of serious morbidities among the cohorts were comparable (robotic: 33% vs. open: 24%, p=0.70). Eleven (36%) patients are actively attempting pregnancy and three have achieved pregnancy. The median time of follow up is 17.0 months (range 0.30-64.9 months). There are no documented recurrences. CONCLUSIONS: RRT results in less blood loss and decreased length of hospital stay with no compromise in histopathologic outcomes. PMID- 22035806 TI - Phase II trial of adjuvant pelvic radiation "sandwiched" between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma. AB - OBJECTIVE: To evaluate the safety and survival in women treated with adjuvant pelvic radiation "sandwiched" between six cycles of paclitaxel and carboplatin chemotherapy with completely resected UPSC. METHODS: Surgically staged women with UPSC (FIGO stage 1-4) and no visible residual disease were enrolled. Treatment involved paclitaxel (175 mg/m(2)) and carboplatin (AUC=6.0-7.5) every 21 days for 3 doses, followed by radiation therapy (RT), followed by an additional 3 cycles of paclitaxel and carboplatin (AUC=5-6). Survival analysis, using Kaplan-Meier methods, was performed on patients who completed at least 3 cycles of chemotherapy and RT. RESULTS: A total of 81 patients were enrolled, of which 72 patients completed the first 3 cycles of chemotherapy followed by prescribed RT. Median age was 67 years (range: 43-82 years). 59/72 (82%) had disease confined to the uterus and 13/72 (18%) had completely resected extra-uterine disease (stage 3 and 4). 65 (83%) completed the protocol. Overall PFS and OS for combined stage 1 and 2 patients was 65.5 +/- 3.6 months and 76.5 +/- 4.3 months, respectively. PFS and OS for combined stage 3 and 4 patients was 25.8 +/- 3.0 and 35.9 +/- 5.3 months, respectively. Three-year % survival probability for stage 1 and 2 patients was 84% and for stage 3 and 4 patients was 50%. Of the 435 chemotherapy cycles administered, there were 11(2.5%) G3/G4 non-hematologic toxicities. 26(6.0%) cycles had dose reductions and 37(8.5%) had dose delays. CONCLUSIONS: Compared to prior studies of single modality adjuvant therapy, RT "sandwiched" between paclitaxel and carboplatin chemotherapy is well-tolerated and highly efficacious in women with completely resected UPSC. PMID- 22035809 TI - Quality of life and emotional distress in early stage and locally advanced cervical cancer patients: a prospective, longitudinal study. AB - OBJECTIVES: This prospective, longitudinal study investigates QoL issues and emotional distress in early stage cervical cancer (ECC) patients undergoing radical surgery (RS) and in locally advanced cervical cancer (LACC) patients triaged to chemoradiation (CT/RT) followed by RS. METHODS: The Global Health Status scale of EORTC QLQ-C30 (GHS), the EORTC QLQ-CX24 (CX24) and the Hospital Anxiety and Depression Scale (HADS) questionnaire were administered at baseline, and after 3, 6, and 12 months from surgery. For LACC patients QoL assessment was also performed after CT/RT. Statistical analysis was performed by the ANOVA for repeated measures and the Between Subject test. RESULTS: In ECC and LACC patients, the GHS scores improved over time (5.5% difference in mean scores compared to baseline in ECC, and 7.0% difference in mean score compared to baseline in LACC patients). An early worsening of lymphedema scores was documented in ECC cases (14.6% difference in mean values compared to baseline, p value=0.001), and in LACC patients (difference up to 28.3% of mean values, value=0.0001). Menopausal symptoms persistently worsened over time reaching >15% difference of mean values compared to baseline in both groups. Sexual activity scores markedly improved both in ECC and LACC patients (difference of mean score values compared to baseline was 16.5% in ECC, and 6.7% in LACC patients). Both ECC and LACC patients experienced an improvement of anxiety scores. CONCLUSIONS: Lymphedema and menopausal symptoms were the most disabling treatment-related sequelae; the amount of QoL issues and their multifaceted aspects require the cooperation of multidisciplinary teams. PMID- 22035810 TI - Basophils in allergic immune responses. AB - Basophils are rare effector cells of the innate immune system. They are generally associated with type 2 immune responses that develop during helminth infections and allergic reactions. The role of basophils for initiation and execution of allergic immune responses is not well understood. Over the past few years new tools have been generated to study the function of basophils in mouse models. Depending on the experimental systems used conflicting results were obtained with regard to the role of basophils for initiation and execution of immune responses against allergens and helminths. This review highlights the current knowledge about basophil in vivo functions with a focus on the role of basophils for allergic responses like asthma, allergic skin diseases and anaphylaxis. PMID- 22035811 TI - Influencing safe perioperative practice through demonstrating relevance. PMID- 22035812 TI - You spoke, we listened: implementing AORN recommended practices. PMID- 22035813 TI - Recommended practices: coming to your neighborhood. PMID- 22035814 TI - Implementing AORN recommended practices for prevention of deep vein thrombosis. AB - One to two people per 1,000 are affected by deep vein thrombosis (DVT) or pulmonary embolism in the United States each year. AORN published its new "Recommended practices for prevention of deep vein thrombosis" to guide perioperative RNs in establishing organization-wide protocols for DVT prevention. Strategies for successful implementation of the recommended practices include taking a multidisciplinary approach to protocol development, providing education and guidance for performing preoperative patient assessments and administering DVT prophylaxis, and having appropriate resources and the facility's policy and procedure for DVT prevention readily available in the practice setting. Hospital and ambulatory patient scenarios have been included as examples of appropriate execution of the recommended practices. PMID- 22035815 TI - Health care worker safety in surgery. AB - Nursing is ranked as one of the occupations with the most incidences of workplace related injury and illness. The six types of injury risk specific to the perioperative environment are biological, ergonomic, chemical, physical, psychosocial, and cultural in nature. Strategies to improve safety include the use of engineering controls to change the work environment, the equipment used, and how the work is done; administrative controls, such as implementing policies and procedures to develop a culture of safety; and behavioral controls that individuals can exercise to reduce the risk of injury. In addition, every perioperative RN is responsible for following safety policies and has the responsibility to identify safety hazards, take appropriate actions, and report the hazards through appropriate channels. PMID- 22035816 TI - Using concept maps in perioperative education. AB - Critical thinking and clinical decision making are essential components of the knowledge and skills acquired in the perioperative education process. Although traditional didactic teaching methods remain predominant teaching strategies in perioperative nursing education, programs should include a variety of methods and tools to enhance learning of a considerable amount of complex material. Concept mapping is an active teaching strategy that can be used in nursing education to facilitate the development of critical thinking and decision-making skills. A concept map is a tool consisting of a main idea, subconcepts, and cross-links that organizes knowledge by showing relationships between concepts. Different types of maps can be used to present different types of learning material, depending on the focus of the lesson. Complex knowledge (eg, perioperative technology) can be better learned and retained when the brain works to organize information in a hierarchical framework and the information is built up with interacting concepts. PMID- 22035817 TI - Bloodborne pathogen violations: compliance is key to prevention. PMID- 22035818 TI - Changing perioperative practice in an Indonesian hospital: part II of II. PMID- 22035822 TI - Reaction to dye. PMID- 22035823 TI - Achieving hemostasis with topical hemostats: making clinically and economically appropriate decisions in the surgical and trauma settings. AB - Achieving hemostasis is a crucial focus of clinicians working in surgical and trauma settings. Topical hemostatic agents-including mechanical hemostats, active hemostats, flowable hemostats, and fibrin sealants-are frequently used in efforts to control bleeding, and new options such as hemostatic dressings, initially used in combat situations, are increasingly being used in civilian settings. To achieve successful hemostasis, a number of vital factors must be considered by surgeons and perioperative nurses, such as the size of the wound; bleeding severity; and the efficacy, possible adverse effects, and method of application of potential hemostatic agents. Understanding how and when to use each of the available hemostatic agents can greatly affect clinical outcomes and help to limit the overall cost of treatment. PMID- 22035824 TI - Lanthanide-DTPA grafted silica nanoparticles as bimodal-imaging contrast agents. AB - The design and synthesis of a combined MRI-optical probe for bio-imaging are reported. The materials studied join the properties of lanthanide (Ln(3+)) complexes and nanoparticles (NPs), offering an excellent solution for bimodal imaging. The hybrid SiO(2)@APS/DTPA:Gd:Ln (Ln = Eu(3+) or Tb(3+)) (APS: 3 aminopropyltriethoxysilane, DTPA: diethylenetriamine pentaacetic acid) system increases the payload of the active magnetic centre (Gd(3+)) and introduces a Ln(3+) long-life excited state (Eu(3+): 0.35 +/- 0.02 ms, Tb(3+): 1.87 +/- 0.02 ms), with resistance to photobleaching and sharp emission bands. The Eu(3+) ions reside in a single low-symmetry site. Although the photoluminescence emission is not influenced by the simultaneous presence of Gd(3+) and Eu(3+), a moderate r(1) increase and a larger enhancement of r(2) are observed, particularly at high fields, due to susceptibility effects on r(2). The presence of Tb(3+) instead of Eu(3+) further raises r(1) but decreases r(2). These values are constant over a wide (5-13) pH range, indicating the paramagnetic NPs stability and absence of leaching. The uptake of NPs by living cells is fast and results in an intensity increase in the T(1)-weighted MRI images. The optical properties of the NPs in cellular pellets are also studied, confirming their potential as bimodal imaging agents. PMID- 22035825 TI - Catapult effect in pole vaulting: is muscle coordination determinant? AB - This study focused on the phase between the time of straightened pole and the maximum height (HP) of vaulter and aimed at determining the catapult effect in pole vaulting on HP. Seven experienced vaulters performed 5-10 vaults recorded by two video cameras, while the surface electromyography (sEMG) activity of 10 upper limbs muscles was recorded. HP was compared with an estimated maximum height (HP(est)) allowing the computation of a push-off index. Muscle synergies were extracted from the sEMG activity profiles using a non-negative matrix factorization algorithm. No significant difference (p>0.47) was found between HP(est) (4.64+/-0.21m) and HP (4.69+/-0.23m). Despite a high inter-individual variability in sEMG profiles, two muscle synergies were extracted for all the subjects which accounted for 96.1+/-2.9% of the total variance. While, the synergy activation coefficients were very similar across subjects, a higher variability was found in the muscle synergy vectors. Consequently, whatever the push-off index among the pole vaulters, the athletes used different muscle groupings (i.e., muscle synergy vectors) which were activated in a similar fashion (i.e., synergy activation coefficients). Overall, these results suggested that muscle coordination adopted between the time of straightened pole and the maximum height does not have a major influence on HP. PMID- 22035826 TI - Effects of 2 exercise training programs on physical activity in daily life in patients with COPD. AB - BACKGROUND: The effects of different exercise training programs on the level of physical activity in daily life in patients with COPD remain to be investigated. OBJECTIVE: In patients with COPD we compared the effects of 2 exercise/training regimens (a high-intensity whole-body endurance-and-strength program, and a low intensity calisthenics-and-breathing-exercises program) on physical activity in daily life, exercise capacity, muscle force, health-related quality of life, and functional status. METHODS: We randomized 40 patients with COPD to perform either endurance-and-strength training (no. = 20, mean +/- SD FEV(1) 40 +/- 13% of predicted) at 60-75% of maximum capacity, or calisthenics-and-breathing-exercises training (no. = 20, mean +/- SD FEV(1) 39 +/- 14% of predicted). Both groups underwent 3 sessions per week for 12 weeks. Before and after the training programs the patients underwent activity monitoring with motion sensors, incremental cycle-ergometry, 6-min walk test, and peripheral-muscle-force test, and responded to questionnaires on health-related quality of life and functional status (activities of daily living, pulmonary functional status, and dyspnea). RESULTS: Time spent active and energy expenditure in daily life were not significantly altered in either group. Exercise capacity and muscle force significantly improved only in the endurance-and-strength group. Health-related quality of life and functional status improved significantly in both groups. CONCLUSIONS: Neither training program significantly improved time spent active or energy expenditure in daily life. The training regimens similarly improved quality of life and functional status. Exercise capacity and muscle force significantly improved only in the high-intensity endurance-and-strength group. PMID- 22035827 TI - Noninvasive ventilation failure: the answer is blowing in the leaks. PMID- 22035828 TI - Prolonged mechanical ventilation: are you a lumper or a splitter? PMID- 22035829 TI - Diagnosing COPD: high time for a paradigm shift. PMID- 22035830 TI - Staffing the respiratory care department: new considerations. PMID- 22035831 TI - Ventilator software version markedly affects time to trigger and time delay. PMID- 22035832 TI - Is noninvasive ventilation possible only in New Jersey? PMID- 22035833 TI - Prognostic significance of neuroendocrine differentiation in prostate adenocarcinoma. AB - Much progress has been made toward an understanding of the development and progression of prostate cancer (PC) and the factors that drive the development of androgen independence. Neuroendocrine (NE) cells may provide an intriguing link between NE cell differentiation (NED) and tumor progression in PC. NED in PC generally confers a more aggressive clinical behavior and less favorable prognosis than conventional PC. In this article, we review the known functions of NE cells in PC and discuss the current knowledge on stimulation of cancer proliferation, invasion, apoptosis resistance, serum and immunohistochemical markers, and the prognostic significance of NED in human PC. PMID- 22035834 TI - [Causes of early mortality after liver transplantation: a twenty-years single centre experience]. AB - OBJECTIVE: To define the causes of mortality of patients who died within the first three months after a liver transplantation. TYPE OF STUDY: Retrospective, observational, and single centre study. PATIENTS AND METHODS: Between March 1989 and July 2010, all patients who died within three months after a liver transplantation were included. Demographic characteristics, preoperative and peroperative data, donor characteristics, postoperative complications and causes of mortality were collected. RESULTS: Among the 788 performed liver transplantations, 76 patients died in intensive care unit (11%). The main indications of liver transplantation were alcoholic cirrhosis (30%), hepatitis C (28%), hepatocarcinoma (15%), primitive or secondary biliary cirrhosis (10%). Fifty percent of the patients were categorized as Child C. The main causes of death were non-function or dysfunction with retransplantation contra-indication graft (18%), sepsis (18%), neurological complications (12%), hemorrhagic shock (13%), (9%), multiorgan failures (5%), cardiac complications (6%). CONCLUSION: In this study, the main causes of mortality were infectious, neurological and hemorrhagic. These results emphasize the necessity for better control of sepsis, haemorrhage and immunosupressors. PMID- 22035835 TI - [State of the art. Publications of French emergency's teams since 5 years]. AB - INTRODUCTION: The development of emergency medicine in France and its valuation can take place only through acknowledged scientific publications. The aim of our study was to analyze the publications of French teams in emergency medicine since 2006. MATERIAL AND METHODS: Observational, descriptive study, from January 1st, 2006 to December 31st, 2010 including, thanks to Medline, studies related to emergency medicine with, as keywords, "medicine d'urgences; urgences; emergency; emergency medicine; French; France" the names of heads of the emergency departments, of the urgent medical aid services (samu) and of anaesthetics services in mainland France. Data collection focused on the type of study, subject, place of conducting the study and grade of international quality. RESULTS: Three hundred and twenty-five publications were listed: 39% (n=126) of the studies were carried out in prehospital. We identified 28% of observational studies (n=92), 20% of randomized prospective (n=66), 19% of cohorts (n=62), 18% of case reports (n=59), 10% of clarifications (n=32) and 4% of general reviews (n=11). The most frequent theme was the cardiology (38% of cases). The most favourite journal was the Annales francaises d'anesthesie et de reanimation (Afar) (18%, n=57). CONCLUSION: The release of French studies in emergency medicine is increasing, with an improvement in the quality of the published studies. All these results demonstrate the progress made since five years in emergency medicine in France but also the work that remains to be done in our rising medical specialization. PMID- 22035836 TI - The end and after: how dying cells impact the living organism. AB - All cells die, but the manner of death dictates interactions with living cells and consequences for the organism, especially with respect to the immune response. Here we discuss the different modes of cell death as they relate to this rapidly evolving field. PMID- 22035837 TI - Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. AB - Prompt and efficient clearance of apoptotic cells is necessary to prevent secondary necrosis of dying cells and to avoid immune responses to autoantigens. Recent studies have shed light on how apoptotic cells through soluble "find-me" signals advertise their presence to phagocytes at the earliest stages of cell death. Phagocytes sense the find-me signal gradient, and in turn the presence of dying cells, and migrate to their vicinity. The apoptotic cells also expose specific "eat-me" signals on their surface that are recognized by phagocytes through specific engulfment receptors. This review covers the recent progress in the areas of find-me and eat-me signals and how these relate to prompt and immunologically silent clearance of apoptotic cells. PMID- 22035838 TI - Cell death in the maintenance and abrogation of tolerance: the five Ws of dying cells. AB - The mammalian immune system continually faces death in the form of its own dead and dying cells that arise during normal tissue turnover, infections, cellular damage, and cancer. Complex decisions must then be made that will permit a protective response to pathogens, while at the same time destroying tumors but not attacking vital systems of the host that could lead to autoimmunity. By using an investigative technique termed the five Ws (who, what, when, where, and why), we will examine how the immune system responds to antigens generated via cell death. This analysis will give us a better understanding of the molecular differences fundamental to tolerogenic or immunogenic cell death, the cells that sense and react to the dead cells, and the consequences of these fundamental elements on the maintenance or abrogation of tolerance. PMID- 22035840 TI - Dying to replicate: the orchestration of the viral life cycle, cell death pathways, and immunity. AB - Manipulation of cell death pathways has been identified as a common feature of host-microbe interactions. We examine two examples: influenza A as a representative acute infection and cytomegalovirus as an example of chronic infection. From the perspective of viral entry, replication, and transmission, we identify points of interconnection with the host response to infection, namely the induction of host cell death, inflammation, and immunity. Following from this analysis, we argue that the evolution and fine-tuned regulation of death associated genes may result from constant microbial pressure--past and present- that helped to support and coordinate cell death programs within the host. Interestingly, the delay in host cell death allows time for the virus to replicate while perturbations in cell death allow the host cell to initiate an immune response. This may represent a genetically encoded trade-off ensuring survival of both host and virus, or it may be a part of the complex agenda of infectious microbes. PMID- 22035839 TI - Tumor promotion via injury- and death-induced inflammation. AB - Inhibition of programmed cell death is considered to be a major aspect of tumorigenesis. Indeed, several key oncogenic transcription factors, such as NF kappaB and STAT3, exert their tumor-promoting activity at least in part through upregulation of survival genes. However, many cancers develop in response to chronic tissue injury, in which the resulting cell death increases the tumorigenic potential of the neighboring cells. In this review, we discuss a resolution to this paradox based on cell death-mediated induction of tumor promoting inflammatory cytokines, which enhance cell survival and trigger compensatory proliferation in response to tissue injury. PMID- 22035841 TI - Dynamiting viruses with MxA. AB - The crystal structure of the interferon-induced member of the dynamin family MxA presented by Gao et al. (2011) in this issue of Immunity reveals the molecule's higher-order structure, thereby providing insight into the protein's antiviral action as a molecular machine. PMID- 22035842 TI - Dual face apoptotic machinery: from initiator of apoptosis to guardian of necroptosis. AB - In this issue of Immunity, Bonnet et al. (2011) show that skin-specific ablation of the adaptor protein FADD sensitizes keratinocytes to RIPK3-dependent necrotic cell death, which leads to severe skin inflammation. PMID- 22035843 TI - Memory: the incomplete unhappening of differentiation. AB - The signals that regulate the differentiation of central and effector memory T cells remain unclear. In this issue of Immunity, Pepper et al. (2011) and Marshall et al. (2011) implicate the differential expression of transcription factors in driving memory subtypes. PMID- 22035844 TI - Orphan cytokine reveals IL-17 family secret. AB - The biology of interleukin-17C (IL-17C) has remained largely a mystery for more than a decade. Chang et al. (2011), in this issue of Immunity, and two other reports (Song et al., 2011; Ramirez-Carrozzi et al., 2011) demonstrate that IL 17C has broad functions in a variety of tissues. PMID- 22035845 TI - The DNA-binding protein CTCF limits proximal Vkappa recombination and restricts kappa enhancer interactions to the immunoglobulin kappa light chain locus. AB - Regulation of immunoglobulin (Ig) V(D)J gene rearrangement is dependent on higher order chromatin organization. Here, we studied the in vivo function of the DNA binding zinc-finger protein CTCF, which regulates interactions between enhancers and promoters. By conditional deletion of the Ctcf gene in the B cell lineage, we demonstrate that loss of CTCF allowed Ig heavy chain recombination, but pre-B cell proliferation and differentiation was severely impaired. In the absence of CTCF, the Igkappa light chain locus showed increased proximal and reduced distal Vkappa usage. This was associated with enhanced proximal Vkappa and reduced Jkappa germline transcription. Chromosome conformation capture experiments demonstrated that CTCF limits interactions of the Igkappa enhancers with the proximal V(kappa) gene region and prevents inappropriate interactions between these strong enhancers and elements outside the Igkappa locus. Thus, although Ig gene recombination can occur in the absence of CTCF, it is a critical factor determining Vkappa segment choice for recombination. PMID- 22035846 TI - Mast cells condition dendritic cells to mediate allograft tolerance. AB - Peripheral tolerance orchestrated by regulatory T cells, dendritic cells (DCs), and mast cells (MCs) has been studied in several models including skin allograft tolerance. We now define a role for MCs in controlling DC behavior ("conditioning") to facilitate tolerance. Under tolerant conditions, we show that MCs mediated a marked increase in tumor necrosis factor (TNFalpha)-dependent accumulation of graft-derived DCs in the dLN compared to nontolerant conditions. This increase of DCs in the dLN is due to the local production of granulocyte macrophage colony-stimulating factor (GM-CSF) by MCs that induces a survival advantage of graft-derived DCs. DCs that migrated to the dLN from the tolerant allograft were tolerogenic; i.e., they dominantly suppress T cell responses and control regional immunity. This study underscores the importance of MCs in conditioning DCs to mediate peripheral tolerance and shows a functional impact of peripherally produced TNFalpha and GM-CSF on the migration and function of tolerogenic DCs. PMID- 22035847 TI - [Systematic reviews of the literature: what should be known about them]. AB - A systematic review (SR) is an article on the "synthesis of the available evidence", in which a review is performed on the quantitative and qualitative aspects of primary studies, with the aim of summarising the existing information on a particular topic. After collecting the articles of interest the researchers then analyse them and compare the evidence they provide with that from similar ones. The reasons for justifying performing an SR are: when there is uncertainty as regards the effect of an intervention due to there being existing evidence against its real usefulness; when it is desired to know the magnitude of the effect of an intervention; and, when it is desired to analyse the behaviour of an intervention in subject sub-groups. The aim of this article is to perform an update on the basic concepts, indications, strengths and weaknesses of SRs, as well as the development of an SR, the most important potential biases to be taken into account in this type of design, and the basic concepts as regards the meta analysis. Two examples of SR are also included, of use for surgeons, who often come across this type of design when searching for scientific evidence in biomedical journal bases. PMID- 22035848 TI - Effect of triple growth factor controlled delivery by a brushite-PLGA system on a bone defect. AB - Bone regeneration is a complex process that involves multiple cell types, growth factors (GFs) and cytokines. A synergistic contribution of various GFs and a crosstalk between their signalling pathways was suggested as determinative for the overall osteogenic outcome. The purpose of this work was to develop a brushite-PLGA system, which controls the release rate of the integrated growth factors (GFs) to enhance bone formation. The brushite cement implants were prepared by mixing a phosphate solid phase with an acid liquid phase. PDGF (250 ng) and TGF-beta1 (100 ng) were incorporated into the liquid phase. PLGA microsphere-encapsulated VEGF (350 ng) was pre-blended with the solid phase. VEGF, PDGF and TGF-beta1 release kinetics and tissue distributions were determined using iodinated ((125)I) GFs. In vivo results showed that PDGF and TGF beta1 were delivered more rapidly from these systems implanted in an intramedullary defect in rabbit femurs than VEGF. The three GFs released from the brushite-PLGA system remained located around the implantation site (5 cm) with negligible systemic exposure. Bone peak concentrations of approximately 4 ng/g and 1.5 ng/g of PDGF and TGF-beta1, respectively were achieved on day 3. Thereafter, PDGF and TGF-beta1 concentrations stayed above 1 ng/g during the first week. The scaffolds also provided a VEGF peak concentration of nearly 6 ng/g on day 7 and a local concentration of approximately 1.5 ng/g during at least 4 weeks. Four weeks post implantation bone formation was considerably enhanced with the brushite-PLGA system loaded with each of the three GFs separately as well as with the combination of PDGF and VEGF. The addition of TGF-beta1 did not further improve the outcome. In conclusion, the herein presented brushite-PLGA system effectively controlled the release kinetics and localisation of the three GFs within the defect site resulting in markedly enhanced bone regeneration. PMID- 22035849 TI - Microsporidia in household dogs and cats in Iran; a zoonotic concern. AB - Microsporidia in dogs and cats is primarily caused by the obligate, intracellular parasite Encephalitozoon cuniculi, which is a member of the phylum Microsporidia. The aim of the current study is the detection of this parasite in stool samples of small animals of Iran, by polymerase chain reaction. Microsporidia spp. was found in 31% (31/100) of dogs (E. cuniculi (18/100), Encephalitozoon bieneusi (8/100) and Encephalitozoon intestinalis (5/100)), and 7.5% (3/40) of the specimens obtained from cats were infected with E. bieneusi. Sequencing of PCR products confirmed these results. In conclusion, Microsporidia infection seems to be fairly common in pet animals of Iran, especially in dogs. This finding could indicate the importance of pet animals as zoonotic reservoirs of microsporidial human infections. PMID- 22035850 TI - Doramectin resistance in Haemonchus contortus on an alpaca farm in Belgium. AB - Parasitism by gastrointestinal nematodes is a health concern in New World Camelids (NWC) worldwide, and anthelmintic treatment is often needed for parasite control. Although anthelmintic resistance has been reported in ruminants worldwide, data in NWC are only scarce. In the present study, a case of suspected doramectin resistance in alpacas was examined. A field efficacy study was conducted for the evaluation of two different dosages of doramectin using a faecal egg count reduction test. A group of 8 alpacas was treated with a subcutaneous injection of doramectin at 0.2mg/kg bodyweight. Individual faecal samples were collected before treatment and 7 days after treatment. The faecal egg counts indicated a treatment efficacy of only 68%. To determine whether the treatment failure was caused by true anthelmintic resistance or suboptimal dosage in this animal species, a group of 4 alpacas was subsequently treated at 0.3mg/kg bodyweight. Faecal egg counts 7 days post treatment were reduced by only 41%, indicating that the treatment failure was more likely to be caused by the presence of resistant parasites on this farm. Coprocultures of faecal samples collected after treatment indicated the presence of 98.5% Haemonchus contortus and a small percentage of Cooperia oncophora (<1.5%). A controlled efficacy trial in sheep, for which the optimal dosage of doramectin is known, was conducted to ensure that this truly was a case of resistant parasites. Infective larvae collected from the faeces of these alpacas were used to infect eight nematode free lambs. These lambs were assigned to one of two groups based on faecal egg counts post infection. One group was treated with doramectin injectable at 0.2mg/kg bodyweight, the other group served as a non treated control group. Pharmacokinetics indicated that the doramectin treatment was adequate, yet an efficacy of only 16% was determined on day 7 after treatment. Identification of the larvae after treatment revealed 100% H. contortus. On day 7 after treatment, H. contortus worm counts were only reduced by 8% in the treated lambs. The results of the present study report for the first time a case of doramectin resistance in alpacas, mainly in H. contortus. PMID- 22035851 TI - Acute effects of indacaterol on lung hyperinflation in moderate COPD: a comparison with tiotropium. AB - BACKGROUND: Evidence has been provided that high-dose indacaterol (300 MUg) can reduce lung hyperinflation in moderate-to-severe chronic obstructive pulmonary disease (COPD). AIM: To study whether low-dose indacaterol (150 MUg) also reduces lung hyperinflation in comparison with the recommended dose of tiotropium (18 MUg) in moderate COPD. METHODS: This was a multicenter, randomized, blinded, 3 period cross-over, placebo-controlled study. Spirometry and lung volumes were measured before and 30, 60, 120, 180 and 240 min after the administration of single-doses of indacaterol, tiotropium, or placebo. The primary end-point was the change in peak inspiratory capacity (IC). The area under the 4-h curve (AUC(0 4)) for IC, 1-s forced expiratory volume (FEV(1)) and forced vital capacity (FVC) were secondary variables. RESULTS: 49 patients completed the study. On average, peak IC and AUC(0-4) for IC were significantly greater after indacaterol than placebo by 177 mL (p = 0.007) and 142 mL (p = 0.001), respectively. Differences in peak IC and AUC(0-4) for IC between tiotropium and placebo were 120 mL (p = 0.07) and 85 mL (p = 0.052), respectively. Differences between indacaterol and tiotropium were statistically insignificant. Peak IC increased by >20% in 12 patients with indacaterol and 9 with tiotropium (p = 0.001), and by >30% in 8 patients with indacaterol and 3 with tiotropium (p = 0.001). The effects of indacaterol and tiotropium on FEV(1) and FVC were statistically significant vs placebo. CONCLUSIONS: Low-dose indacaterol has a bronchodilator effect that is similar to the recommended dose of tiotropium, but it is slightly superior in reducing lung hyperinflation. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00999908. PMID- 22035852 TI - Extended diagnostic criteria used for indirect challenge testing in elite asthmatic swimmers. AB - The aim of the study was to investigate the prevalence of asthma with or without exercise induced symptoms among elite and elite aspiring swimmers and to compare sport specific exercise provocation with mannitol provocation. METHODS: 101 adolescent swimmers were investigated with mannitol provocation and sport specific exercise challenge test. Mannitol positivity was defined as either direct FEV(1) PD15 (ordinary criteria) or as beta(2)-reversibility >=15% after challenge (extended criteria). A direct positive exercise test was defined as a drop in FEV(1) of 10% (ordinary criteria) or a difference in FEV of >=15% either spontaneous, variability, or with beta2-agonist, reversibility (extended criteria). RESULTS: We found a high prevalence of mannitol and/or exercise positivity. Twenty-six swimmers were mannitol direct positive and 14 were direct exercise positive using ordinary criteria. Using extended criteria 43 were mannitol positive and 24 were exercise positive. When including reversibility and variability to define a positive test the sensitivity for current asthma with or without exercise induced symptoms increased while the specificity remained roughly unchanged. Direct positivity for mannitol and exercise poorly overlapped using ordinary criteria but improved using extended criteria. CONCLUSION: We found a high prevalence of asthma among elite swimmers. The use of variability and reversibility (liability) as additional criteria to define a positive test provided to our mind relevant information and should be considered. PMID- 22035853 TI - Real-life prospective study on asthma control in Italy: cross-sectional phase results. AB - OBJECTIVES: To estimate the prevalence of partly controlled and uncontrolled asthmatic patients, to evaluate quality of life and healthcare resource consumption. METHODS: Cross-sectional phase followed by a 12-month prospective phase. Asthma Control Test and the EQ-5D were used. RESULTS: 2853 adult patients recruited in 56 Hospital Respiratory Units in Italy were evaluated: 64.4% had controlled asthma, 15.8% partly controlled asthma and 19.8% were uncontrolled. The mean (SD) EQ-5D score was 0.86 (0.17) in controlled, 0.75 (0.20) in partly controlled and 0.69 (0.23) in uncontrolled patients (p<0.001 between groups). The number of patients requiring hospitalization or emergency room visits was lower in controlled (1.8% and 1.6%, respectively) than in partly controlled (5.1% and 11.5%) and uncontrolled (6.4% and 18.6%). A combination of an inhaled corticosteroid and a long-acting beta-2 agonist was the reported therapy by 56.0% of patients, with the rate of controlled asthma and improved quality of life being higher in patients on extrafine beclomethasone/formoterol compared to budesonide/formoterol (p<0.05) and fluticasone/salmeterol (p<0.05 for quality of life). CONCLUSIONS: Asthma control is achieved in a good proportion of Italian patients. Differences may be detected in a real-life setting in favor of extrafine beclomethasone/formoterol combination. PMID- 22035854 TI - Principles of microRNA involvement in human cancers. AB - Naturally occurring microRNAs (miRNAs), small non-coding RNAs of 19 to 24 nucleotides (nt), are encoded in the genomes of invertebrates, vertebrates, and plants. miRNAs act as regulators of gene expression during development and differentiation at the transcriptional, posttranscriptional, and/or translational levels, although most target genes are still elusive. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential processes. In this review, we present principles related to the basic and translational research that has emerged in the last decade, a period that can be truly considered the "miRNA revolution" in molecular oncology. These principles include the regulation mechanism of miRNA expression, functions of miRNAs in cancers, diagnostic values and therapeutic potentials of miRNAs. Furthermore, we present a compendium of information about the main miRNAs that have been identified in the last several years as playing important roles in cancers. Also, we orient the reader to several additional reviews that may provide a deeper understanding of this new and exciting field of research. PMID- 22035855 TI - Cancer epigenetics: a perspective on the role of DNA methylation in acquired endocrine resistance. AB - Epigenetic mechanisms, including DNA methylation, are responsible for determining and maintaining cell fate, stably differentiating the various tissues in our bodies. Increasing evidence shows that DNA methylation plays a significant role in cancer, from the silencing of tumor suppressors to the activation of oncogenes and the promotion of metastasis. Recent studies also suggest a role for DNA methylation in drug resistance. This perspective article discusses how DNA methylation may contribute to the development of acquired endocrine resistance, with a focus on breast cancer. In addition, we discuss DNA methylome profiling and how recent developments in this field are shedding new light on the role of epigenetics in endocrine resistance. Hormone ablation is the therapy of choice for hormone-sensitive breast tumors, yet as many as 40% of patients inevitably relapse, and these hormone refractory tumors often have a poor prognosis. Epigenetic studies could provide DNA methylation biomarkers to predict and diagnose acquired resistance in response to treatment. Elucidation of epigenetic mechanisms may also lead to the development of new treatments that specifically target epigenetic abnormalities or vulnerabilities in cancer cells. Expectations must be tempered by the fact that epigenetic mechanisms of endocrine resistance remain poorly understood, and further study is required to better understand how altering epigenetic pathways with therapeutics can promote or inhibit endocrine resistance in different contexts. Going forward, DNA methylome profiling will become increasingly central to epigenetic research, heralding a network-based approach to epigenetics that promises to advance our understanding of the etiology of cancer in ways not previously possible. PMID- 22035856 TI - Spatial autocorrelation calculations of the nine malignant neoplasms in Taiwan in 2005-2009: a gender comparison study. AB - Spatial analytical techniques and models are often used in epidemiology to identify spatial anomalies (hotspots) in disease regions. These analytical approaches can be used to identify not only the location of such hotspots, but also their spatial patterns. We used spatial autocorrelation methodologies, including Global Moran's I and Local Getis-Ord statistics, to describe and map spatial clusters and areas in which nine malignant neoplasms are situated in Taiwan. In addition, we used a logistic regression model to test the characteristics of similarity and dissimilarity between males and females and to formulate the common spatial risk. The mean found by local spatial autocorrelation analysis was used to identify spatial cluster patterns. We found a significant relationship between the leading malignant neoplasms and well documented spatial risk factors. For instance, in Taiwan, the geographic distribution of clusters where oral cavity cancer in males is prevalent was closely correspond to the locations in central Taiwan with serious metal pollution. In females, clusters of oral cavity cancer were closely related with aboriginal townships in eastern Taiwan, where cigarette smoking, alcohol drinking, and betel nut chewing are commonplace. The difference between males and females in the spatial distributions was stark. Furthermore, areas with a high morbidity of gastric cancer were clustered in aboriginal townships where the occurrence of Helicobacter pylori is frequent. Our results revealed a similarity between both males and females in spatial pattern. Cluster mapping clarified the spatial aspects of both internal and external correlations for the nine malignant neoplasms. In addition, using a method of logistic regression also enabled us to find differentiation between gender-specific spatial patterns. PMID- 22035857 TI - ABO blood type is associated with endometrial cancer risk in Chinese women. AB - ABO blood type has been associated with risk of several malignancies. However, results are not consistent. In this population-based case-control study including 1204 incident endometrial cancer cases and 1212 population controls, we examined the association of self-reported serologic blood type with endometrial cancer risk using a logistic regression model. Women with endometrial cancer were more likely to have blood type A. Compared to women with blood type O, the adjusted odds ratios for endometrial cancer were 1.00 [95% confidence interval (CI), 0.79 1.28] for type B, 1.24 (95% CI, 0.90-1.69) for type AB, and 1.50 (95% CI, 1.19 1.90) for type A. A significant dose-response relationship was observed for cancer risk and level of antigen A (P for trend = 0.0003). The positive association of blood type A with cancer risk was observed regardless of menopausal status, body mass index, oral contraceptive use, or family cancer history. Our results suggest that ABO blood type may be involved in the development of endometrial cancer. PMID- 22035858 TI - Stage T1N0M0 renal cell carcinoma: the prognosis in Asian patients. AB - The prognostic features of T1N0M0 renal cell carcinoma (RCC) in Asian patients have not been well explored in large sample studies. In this study, we retrospectively analyzed the records of 713 patients undergoing nephrectomy for T1N0M0 RCC between 1991 and 2009 in three Asian hospitals. Univariate and multivariate analysis were performed to identify the independent predictive factors for T1N0M0 RCC prognosis among a series of clinicopathological parameters, including age, gender, tumor size, Fuhrman grade, and histological classification. Our results showed that 388 of 713 patients had tumors 4.0 cm or smaller (stage T1a) and 325 of 713 patients had tumors 4.0-7.0 cm in size (stage T1b). Five-year cancer-specific survival (CSS) and recurrence-free survival (RFS) rates for this group of patients were 96.0% and 93.5%, respectively. The patients with T1b RCC had a significantly lower 5-year CSS and RFS rates than did those with T1a RCC (CSS, 93.1% vs. 98.6%, P = 0.026; RFS, 90.0% vs. 96.5%, P < 0.001). Patients with low grade (grades I-II) tumors had a higher 5-year CSS (97.8% vs. 91.2%, P = 0.001) and RFS (95.5% vs. 85.5%, P < 0.001) rate than did those with high grade (grades I-II) tumors. More interestingly, when stratifying patients to T1a and T1b groups, the role of grade in distinguishing prognosis could be only observed in patients with T1b disease. Cox regression showed tumor size and Fuhrman grade were significant in predicting CSS and RFS. Our study suggests that the prognosis of patients with T1N0M0 RCC is excellent, and these results are comparable to previously reported studies in Western patients. Furthermore, our data indicates that patients with T1b disease and high Fuhrman grade have high risk of tumor recurrence and death, thus requiring more frequent follow-up. PMID- 22035859 TI - The effect of childbirth on carcinogenesis of DMBA-induced breast cancer in female SD rats. AB - Many epidemiologic and clinical studies have indicated that the frequency of breast cancer was lower in parous women than in nulliparous women. Moreover, the incidence of breast cancer has been reported to be lower in women with early childbirth than in women with late childbirth. To verify the effect of childbirth and the age at first childbirth on carcinogenesis and progression of breast cancer, we induced breast cancer by 7,12-dimethylbenanthracene (DMBA) in 120 female Sprague-Dawley (SD) rats, and divided them into control or experimental (DMBA-treated) nulliparous, early childbirth, and late childbirth groups to observe the incidence, latency, and size of breast cancer. Argyrophilic nucleolar organizer regions (AgNOR) count and the expression of C-erbB-2, proliferating cell nuclear antigen (PCNA), Ki-67, and minichromosome maintenance protein 2 (MCM2) in breast cancer tissues were detected by immunohistochemistry. The breast cancer incidences were 95.0%, 16.7%, and 58.8% in the experimental nulliparous, early childbirth, and late childbirth groups, respectively (all P < 0.05). Between any two of these groups, the latency was significantly different, but tumor size was similar. AgNOR count and the expression of C-erbB-2, PCNA, Ki-67, and MCM2 were significantly higher in the experimental nulliparous group than in the experimental early or late childbirth groups (P < 0.05), but no significant differences were observed between the latter two groups. Taken together, the results suggest that childbirth, especially early childbirth, can reduce the incidence and postpone the onset of DMBA-induced breast cancer. PMID- 22035860 TI - Water-filled balloon in the postoperative resection cavity improves dose distribution to target volumes in radiotherapy of maxillary sinus carcinoma. AB - Postoperative radiotherapy is a major treatment for patients with maxillary sinus carcinoma. However, the irregular resection cavity poses a technical difficulty for this treatment, causing uneven dose distribution to target volumes. In this study, we evaluated the dose distribution to target volumes and normal tissues in postoperative intensity-modulated radiotherapy (IMRT) after placing a water filled balloon into the resection cavity. Three postoperative patients with advanced maxillary sinus carcinoma were selected in this trial. Water-filled balloons and supporting dental stents were fabricated according to the size of the maxillary resection cavity. Simulation CT scans were performed with or without water-filled balloons, IMRT treatment plans were established, and dose distribution to target volumes and organs at risk were evaluated. Compared to those in the treatment plan without balloons, the dose (D98) delivered to 98% of the gross tumor volume (GTV) increased by 2.1 Gy (P = 0.009), homogeneity index (HI) improved by 2.3% (P = 0.001), and target volume conformity index (TCI) of 68 Gy increased by 18.5% (P = 0.011) in the plan with balloons. Dosimetry endpoints of normal tissues around target regions in both plans were not significantly different (P > 0.05) except for the optic chiasm. In the plan without balloons, 68 Gy high-dose regions did not entirely cover target volumes in the ethmoid sinus, posteromedial wall of the maxillary sinus, or surgical margin of the hard palate. In contrast, 68 Gy high-dose regions entirely covered the GTV in the plan with balloons. These results suggest that placing a water-filled balloon in the resection cavity for postoperative IMRT of maxillary sinus carcinoma can reduce low-dose regions and markedly and simultaneously increase dose homogeneity and conformity of target volumes. PMID- 22035862 TI - [Calcitonin: indications and interpretation]. AB - Calcitonin is the sensitive and specific marker of the medullary thyroid cancers. It is a diagnostic, pronostic and follow-up marker. Medullary thyroid cancer is a rare disease representing 4% of the thyroid cancers and occurring in 0.4% of nodular thyroid pathology. The use of sex specific adults normal ranges allows a better interpretation of the moderately elevated calcitonin levels. Hypercalcitoninaemia non due to medullary thyroid cancer are attributed mainly to male sex, tobacco use, overweight, renal failure and other endocrine tumors. CT is associated to carcinoembryonic antigen and possible procalcitonin assays. Calcitonin can be assayed in the wash-out fluid of the fine needle aspiration too. Stimulation tests give poor additional diagnostic information and are about to be abandoned. PMID- 22035861 TI - Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature. AB - Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively. PMID- 22035863 TI - Molecular genetics of cancer and tumorigenesis: Drosophila models. PMID- 22035864 TI - Tumor invasion and metastasis in Drosophila: a bold past, a bright future. AB - Invasion and metastasis are the most deadly hallmarks of cancer. Once a cancer has acquired the ability to colonize new sites in the body it becomes dramatically more difficult to treat. This has made it a focus of much of cancer research. The humble fruit fly, Drosophila melanogaster, has despite its relative simplicity, made significant contributions to the understanding of tumor progression. In this review we outline and highlight those with an emphasis on modeling the genetic and epigenetic changes required for invasion and metastasis. We will revisit the early years of cancer modeling in Drosophila where the first parallels were drawn between Drosophila and vertebrate neoplasms and highlight recent advances using genetic screens and interactions with the epithelial microenvironment and innate immune system. We focus on the power and limitations of current fly models of metastasis. PMID- 22035865 TI - Dysregulation of CDK8 and Cyclin C in tumorigenesis. AB - Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms. In eukaryotes, the transcription of protein coding mRNAs is dependent on RNA polymerase II (Pol II). The multi-subunit transcription cofactor Mediator complex is proposed to regulate most, if not all, of the Pol II-dependent transcription. Here we focus our discussion on two subunits of the Mediator complex, cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC), because they are either mutated or amplified in a variety of human cancers. CDK8 functions as an oncoprotein in melanoma and colorectal cancers, thus there are considerable interests in developing drugs specifically targeting the CDK8 kinase activity. However, to evaluate the feasibility of targeting CDK8 for cancer therapy and to understand how their dysregulation contributes to tumorigenesis, it is essential to elucidate the in vivo function and regulation of CDK8-CycC, which are still poorly understood in multi-cellular organisms. We summarize the evidence linking their dysregulation to various cancers and present our bioinformatics and computational analyses on the structure and evolution of CDK8. We also discuss the implications of these observations in tumorigenesis. Because most of the Mediator subunits, including CDK8 and CycC, are highly conserved during eukaryotic evolution, we expect that investigations using model organisms such as Drosophila will provide important insights into the function and regulation of CDK8 and CycC in different cellular and developmental contexts. PMID- 22035867 TI - Deciphering tumor-suppressor signaling in flies: genetic link between Scribble/Dlg/Lgl and the Hippo pathways. AB - Loss of apico-basal polarity is one of the crucial factors that drives epithelial tumor progression. scribble/discs large/lethal giant larvae (scrib/dlg/lgl), a group of apico-basal polarity genes, were initially identified as members of "neoplastic" tumor-suppressors in flies. The components of the Hippo signaling pathway, which is crucial for organ size control and cancer development, were also identified through Drosophila genetic screens as members of "hyperplastic" tumor-suppressors. Accumulating evidence in recent studies implies that these two tumor-suppressor signaling pathways are not mutually exclusive but rather cooperatively act to give rise to highly malignant tumors. The interaction of these tumor-suppressor pathways could include deregulations of actin cytoskeleton, cell-cell contact, and apical-domain size of the epithelial cell. PMID- 22035866 TI - Extra sex combs, chromatin, and cancer: exploring epigenetic regulation and tumorigenesis in Drosophila. AB - Developmental genetic studies in Drosophila unraveled the importance of Polycomb group (PcG) and Trithorax group (TrxG) genes in controlling cellular identity. PcG and TrxG proteins form histone modifying complexes that catalyze repressive or activating histone modifications, respectively, and thus maintaining the expression status of homeotic genes. Human orthologs of PcG and TrxG genes are implicated in tumorigenesis as well as in determining the prognosis of individual cancers. Recent whole genome analyses of cancers also highlighted the importance of histone modifying proteins in controlling tumorigenesis. Comprehensive understanding of the mechanistic relationship between histone regulation and tumorigenesis holds the promise of significantly advancing our understanding and management of cancer. It is anticipated that Drosophila melanogaster, the model organism that contributed significantly to our understanding of the functional role of histone regulation in development, could also provide unique insight for our understanding of how histone dysregulation can lead to cancer. In this review, we will discuss several recent advances in this regard. PMID- 22035868 TI - Hippo signaling: a hub of growth control, tumor suppression and pluripotency maintenance. AB - The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology. Almost a decade ago, the discovery of the Hippo signaling pathway in Drosophila shed some light on this puzzling issue. The Hippo signaling pathway is highly conserved in both invertebrates and vertebrates, and plays critical roles in animal development. It controls organ size and growth by inhibiting cell proliferation and by promoting apoptosis. Malfunction of the Hippo signaling pathway leads to cancer development and tumorigenesis. Although the core of the signaling pathway is well understood, the upstream inputs and downstream transcriptional regulation are still obscure to us. In this review, we summarize the current understanding of the mechanism and the function of the Hippo signaling pathway and compare its differences between flies and mammals. We underline the crosstalk between the Hippo signaling pathway and other signaling pathways, and the possible roles of the Hippo pathway in stem cell proliferation and self-renewal. PMID- 22035870 TI - Chemical genetics and drug screening in Drosophila cancer models. AB - Drug candidates often fail in preclinical and clinical testing because of reasons of efficacy and/or safety. It would be time- and cost-efficient to have screening models that reduce the rate of such false positive candidates that appear promising at first but fail later. In this regard, it would be particularly useful to have a rapid and inexpensive whole animal model that can pre-select hits from high-throughput screens but before testing in costly rodent assays. Drosophila melanogaster has emerged as a potential whole animal model for drug screening. Of particular interest have been drugs that must act in the context of multi-cellularity such as those for neurological disorders and cancer. A recent review provides a comprehensive summary of drug screening in Drosophila, but with an emphasis on neurodegenerative disorders. Here, we review Drosophila screens in the literature aimed at cancer therapeutics. PMID- 22035871 TI - Personalized participatory medicine: sharing knowledge and uncertainty. AB - Informing patients about risks and benefits of alternative treatment options and choosing between them is becoming a bigger challenge as knowledge about the relationship between the individual's genetic profile and the efficacy and safety of available medications accumulates. Putting personalized medicine into practice requires new modes of information sharing and decision making by patient and physician. This is illustrated by a case study on treatment choices of breast cancer patients following genotyping for CYP2D6, recently published in Genome Medicine.See research article: http://genomemedicine.com/content/3/10/64. PMID- 22035869 TI - Cell competition and its implications for development and cancer. AB - Cell competition is a struggle for existence between cells in heterogeneous tissues of multicellular organisms. Loser cells, which die during cell competition, are normally viable when grown only with other loser cells, but when mixed with winner cells, they are at a growth disadvantage and undergo apoptosis. Intriguingly, several recent studies have revealed that cells bearing mutant tumor-suppressor genes, which show overgrowth and tumorigenesis in a homotypic situation, are frequently eliminated, through cell competition, from tissues in which they are surrounded by wild-type cells. Here, we focus on the regulation of cellular competitiveness and the mechanism of cell competition as inferred from two different categories of mutant cells: (1) slower-growing cells and (2) structurally defective cells. We also discuss the possible role of cell competition as an intrinsic homeostasis system through which normal cells sense and remove aberrant cells, such as precancerous cells, to maintain the integrity and normal development of tissues and organs. PMID- 22035872 TI - Effect of current depression on the association of work-related asthma with adverse asthma outcomes: a cross-sectional study using the Behavioral Risk Factor Surveillance System. AB - BACKGROUND: Depression has been associated with a decreased level of asthma control. The aim of our study was to examine associations between health professional diagnosed work-related asthma (WRA) and current depression and the effect of current depression on the associations of WRA with adverse asthma outcomes. METHOD: We analyzed data from the 2006 and 2008 Behavioral Risk Factor Surveillance System Asthma Call-Back Survey and the Anxiety and Depression Module conducted in 25 states and District of Columbia for ever-employed adults with current asthma. We computed weighted proportions and prevalence ratios adjusted for age, sex, race/ethnicity, education, current employment status, and smoking status. Survey participants who were ever told by a doctor or other health professional that their asthma was related to any job they ever had were determined to have WRA. Participants with current depression were identified using self-report of depressive symptoms. RESULTS: Of ever-employed adults with current asthma, an estimated 9.1% had WRA and 17.0% had current depression. Persons with WRA were significantly more likely than those with non-WRA to have current depression. Persons with either WRA, current depression, or both WRA and current depression were significantly more likely to have adverse asthma outcomes than persons with asthma and neither condition. The associations with adverse asthma outcomes were stronger when both current depression and WRA were present. LIMITATIONS: This is a cross-sectional and hypothesis-generating study. CONCLUSIONS: Depression may play an important role in asthma management and should be considered when assessing patients with asthma and, in particular, those with WRA. PMID- 22035873 TI - Epigenetic reprogramming during plant reproduction and seed development. AB - Epigenetic processes such as DNA methylation are crucial for the development of flowering plants, and for protection of genome integrity via silencing of transposable elements (TEs). Recent advances in genome-wide profiling suggest that during reproduction DNA methylation patterns are at least partially transmitted or even enhanced in the next generation to ensure stable silencing of TEs. At the same time, parent-of-origin specific removal of DNA methylation in the accompanying tissue allows imprinted expression of genes. Here we summarize the dynamics of DNA methylation as a major epigenetic regulatory pathway during reproduction and seed development. PMID- 22035874 TI - Low surface contamination by cis/oxaliplatin during hyperthermic intraperitoneal chemotherapy (HIPEC). AB - AIM: The aim of this study was to evaluate contamination by platinum drugs in the operating room during hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Environmental sampling of 151 wipe samples from surfaces on the HIPEC devices and operating room floors was performed for platinum in six German hospitals during 19 HIPEC procedures. Additionally, 45 wipe samples from surgeons' and perfusionists' protective gloves were analyzed. RESULTS: Platinum concentrations from the HIPEC devices and operating room floors ranged from 0.07 to 110,000 pg/cm(2) (Median: 1.5 pg/cm(2)) with high contamination on the regulation knob and reservoir after HIPEC procedure, particularly when injecting the cytostatic drug into the reservoir via syringe. Samples from perfusionists' and surgeons' protective gloves ranged between 0.01 and 729 ng/pair. CONCLUSIONS: Although sporadically high platinum concentrations on surfaces on the HIPEC device and operating room floor were detected, our study revealed that low surface loads are definitely possible and can be documented by wipe samples. Important factors for achieving low surface contamination are the use of infusion bags instead of syringes for injection of the cytostatic solution, careful cleaning of the device after HIPEC and wearing of two pairs of gloves. PMID- 22035875 TI - Long-term follow-up after fractional flow reserve-guided treatment strategy in patients with an isolated proximal left anterior descending coronary artery stenosis. AB - OBJECTIVES: This study sought to evaluate the long-term clinical outcome of patients with an angiographically intermediate left anterior descending coronary artery (LAD) stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR). BACKGROUND: When revascularization is based mainly on angiographic guidance, a number of hemodynamically nonsignificant stenoses will be revascularized. METHODS: In 730 patients with a 30% to 70% isolated stenosis in the proximal LAD and no significant valvular disease, FFR measurements were obtained to guide treatment strategy. When FFR was >= 0.80, the patients (n = 564) were treated medically (medical group); when FFR was <0.80, the patients (n = 166) underwent a revascularization procedure (revascularization group; 13% coronary artery bypass graft surgery and 87% percutaneous coronary intervention). A 100% long-term clinical follow-up (median follow-up: 40 months) was obtained. The 5-year survival of the medical group was compared with that of a reference population. For each patient, 4 controls were selected from an age- and sex-matched control population. RESULTS: The 5-year survival estimate was 92.9% in the medical group versus 89.6% in the controls (p = 0.74). The mean diameter stenosis was significantly smaller in the medical than in the revascularization group (39 +/- 14% vs. 54 +/- 13%, p < 0.0001), but there was a large overlap between both groups. The 5-year event-free survival estimates (death, myocardial infarction, and target vessel revascularization) were 89.7% and 68.5%, respectively (p < 0.0001). CONCLUSIONS: Medical treatment of patients with a hemodynamically nonsignificant stenosis (FFR >= 0.80) in the proximal LAD is associated with an excellent long-term clinical outcome with survival at 5 years similar to an age- and sex-matched control population. PMID- 22035876 TI - No reason to change the current guidelines on allergy prevention. PMID- 22035877 TI - The effect of single and multiple infections on atopy and wheezing in children. AB - BACKGROUND: The current epidemic of asthma and atopy has been explained by alterations in immune responses related to reduction in childhood infections. However, the findings of epidemiologic studies investigating the association between infection with atopy and asthma have been inconsistent. OBJECTIVE: We sought to investigate the effect of single or multiple infections (pathogen burden) on atopy and wheeze in urban children from Latin America. METHODS: Specific IgE against aeroallergens (sIgE) and skin prick test (SPT) reactivity for the most common local allergens were measured in 1128 children aged 4 to 11 years. Data on wheezing and potential confounders were collected by questionnaire. Infections by 8 pathogens were assessed by using serology and stool examination. Associations of wheeze and atopic outcomes with single and multiple infections were analyzed by means of logistic regression. RESULTS: Negative results for Toxoplasma gondii were associated with a higher prevalence of sIgE (>=0.70 kU/L), whereas negative results for Ascaris lumbricoides, T gondii, herpes simplex virus, and EBV were associated with a higher prevalence of SPT reactivity. Children with 3 or fewer infection markers had a higher prevalence of sIgE and SPT reactivity compared with those with 4 or more infection markers. However, isolated infections or pathogen burden were not associated with the prevalence of atopic or nonatopic wheeze. CONCLUSION: The findings provide support for the idea that the hygiene hypothesis is operating in an urban Latin American context, but its expression is thus far restricted to the atopic status of patients and not the perceived asthma symptoms. PMID- 22035879 TI - Histamine and H1-antihistamines: celebrating a century of progress. AB - In this review we celebrate a century of progress since the initial description of the physiologic and pathologic roles of histamine and 70 years of progress since the introduction of H(1)-antihistamines for clinical use. We discuss histamine and clinically relevant information about the molecular mechanisms of action of H(1)-antihistamines as inverse agonists (not antagonists or blockers) with immunoregulatory effects. Unlike first (old)-generation H(1)-antihistamines introduced from 1942 to the mid-1980s, most of the second (new)-generation H(1) antihistamines introduced subsequently have been investigated extensively with regard to clinical pharmacology, efficacy, and safety; moreover, they are relatively free from adverse effects and not causally linked with fatalities after overdose. Important advances include improved nasal and ophthalmic H(1) antihistamines with rapid onset of action (in minutes) for allergic rhinitis and allergic conjunctivitis treatment, respectively, and effective and safe use of high (up to 4-fold) doses of oral second-generation H(1)-antihistamines for chronic urticaria treatment. New H(1)-antihistamines introduced for clinical use include oral formulations (bilastine and rupatadine), and ophthalmic formulations (alcaftadine and bepotastine). Clinical studies of H(3)-antihistamines with enhanced decongestant effects have been conducted in patients with allergic rhinitis. Additional novel compounds being studied include H(4)-antihistamines with anti-inflammatory effects in allergic rhinitis, atopic dermatitis, and other diseases. Antihistamines have a storied past and a promising future. PMID- 22035880 TI - Genetic CD21 deficiency is associated with hypogammaglobulinemia. AB - BACKGROUND: Complement receptor 2 (CR2/CD21) is part of the B-cell coreceptor and expressed by mature B cells and follicular dendritic cells. CD21 is a receptor for C3d-opsonized immune complexes and enhances antigen-specific B-cell responses. OBJECTIVE: Genetic inactivation of the murine CR2 locus results in impaired humoral immune responses. Here we report the first case of a genetic CD21 deficiency in human subjects. METHODS: CD21 protein expression was analyzed by means of flow cytometry and Western blotting. CD21 transcripts were quantified by using real-time PCR. The CD21 gene was sequenced. Wild-type and mutant CD21 cDNA expression was studied after transfection of 293T cells. Binding of EBV gp350 or C3d-containing immune complexes and induction of calcium flux in CD21 deficient B cells were analyzed by means of flow cytometry. Antibody responses to protein and polysaccharide vaccines were measured. RESULTS: A 28-year-old man presented with recurrent infections, reduced class-switched memory B cells, and hypogammaglobulinemia. CD21 receptor expression was undetectable. Binding of C3d containing immune complexes and EBV-gp350 to B cells was severely reduced. Sequence analysis revealed a compound heterozygous deleterious mutation in the CD21 gene. Functional studies with anti-immunoglobulin- and C3d-containing immune complexes showed a complete loss of costimulatory activity of C3d in enhancing suboptimal B-cell receptor stimulation. Vaccination responses to protein antigens were normal, but the response to pneumococcal polysaccharide vaccination was moderately impaired. CONCLUSIONS: Genetic CD21 deficiency adds to the molecular defects observed in human subjects with hypogammaglobulinemia. PMID- 22035881 TI - Involving service users in the classroom with social work students. AB - The purpose of this paper is to explore and discuss issues related to the requirement by the Scottish Social Services Council (SSSC) and the Scottish Government that service users and carers are partners and stakeholders in social work education. This requirement is one of several that are used by the SSSC in the approval of Scottish Universities to deliver social work courses. This paper explains the developmental process of involving service users and carers as partners in the planning of social work courses at the Robert Gordon University (RGU), Aberdeen. This is illustrated with reference to a group made up of young people ('The Voice of Reason') and also in relation to a group made up of adult service users (the Service User Panel). This short paper suggests there are benefits for student learning if we invite service users and carers to become partners in the teaching/learning process. There are also benefits for teaching staff and indeed for the University itself as a public institution on the basis that an ongoing relationship allows for good partnership working. This enables the University and its staff to be viewed positively and from that vantage point further developments are more likely. At the same time this paper has discussed the need to avoid tokenistic moves through ensuring a sound organisational commitment is made to providing effective support and putting in place enabling structures and processes. Lastly it discusses the broader implications for partnership working in relation to the education and training of students for professional practice. The suggestion is made that such a teaching and learning approach equips the students with good partnership skills and attitudes that will help to inform their practice post-qualification. Interest is expressed in the experiences of other professions who have adopted similar approaches to incorporating service users into students' learning experiences. PMID- 22035883 TI - Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy. AB - OBJECTIVE: To compare efficacy between double-dose methotrexate and single-dose methotrexate for treatment of tubal ectopic pregnancy (EP). METHODS: Between March 2008 and February 2011,157 patients who had tubal EP diagnosed by a non laparoscopic approach and were hemodynamically stable were enrolled in a prospective study in Qassim, Saudi Arabia. The participants were randomized to receive either double-dose (50mg/m(2) intramuscularly on days 0 and 4; group 1) or single-dose (50mg/m(2) intramuscularly on day 0; group 2) methotrexate. Serum human chorionic gonadotropin (beta-hCG) levels were followed until negative. RESULTS: The overall success rate was comparable between groups 1 and 2 (88.6% versus 82.0%, P=0.1). The duration of follow up until negative beta-hCG was shorter in group 1 (P=0.001). Receiver operative characteristics showed that higher cut-off levels of beta-hCG and gestational mass diameter were associated with successful outcome in group 1. Among participants with initial beta-hCG of 3600-5500 mIU/mL, the success rate was higher in group 1 (P=0.03). There was no significant difference between groups in adverse effects. CONCLUSION: For treatment of EP, double-dose methotrexate had efficacy and safety comparable to that of single-dose methotrexate; it had better success among patients with moderately high beta-hCG and led to a shorter follow up. PMID- 22035882 TI - The use of transarterial chemoembolization in the treatment of unresectable hepatocellular carcinoma: a response to the Cochrane Collaboration review of 2011. AB - This commentary is written in response to a recent Cochrane Collaboration review published in March 2011 (1). The authors of this commentary would like to express their concerns over the conclusions of the Cochrane review, which state, "There is no firm evidence to support or refute transarterial chemoembolization (TACE) or transarterial embolization (TAE) for patients with unresectable hepatocellular carcinoma (HCC)." PMID- 22035884 TI - Staphylococcal scalded skin syndrome in the Czech Republic: an epidemiological study. AB - OBJECTIVE: To identify the basic epidemiological characteristics of children hospitalized with diagnosis of Staphylococcal scalded skin syndrome in the Czech Republic in the years 1994-2009. INTRODUCTION: Staphylococcal scalded skin syndrome (SSSS) is a relatively rare disease in childhood. This syndrome was first defined in 1878 by Baron Gottfried Ritter von Rittershainem and belongs to the group of diseases called Burn-like syndromes. It is a bullous skin disease caused by exfoliative toxins which are produced by certain types of Staphyloccocus aureus. Typical structures affected by these toxins are desmosome proteins called Desmoglein-1 located in the stratum granulosum of epidermis. Unlike in Lyell's syndrome or Stevens-Johnson's syndrome, the exfoliation is caused by loss of adhesivity particularly in the stratum granulosum and not by induction of apoptosis in the dermo-epidermal junction. MATERIAL AND METHODS: This retrospective study was conducted on patients hospitalized in the Czech Republic in the period from 1.1.1994 to 31.12.2009. The basic condition for the inclusion in the retrospective study was age under 1 year and hospitalization due to SSSS. A total of 399 children (177 girls) fulfilled the criteria for inclusion into the study. Information was obtained from a central data depository, the Department of Health Information and Statistics, Czech Republic. RESULTS: A total of 399 children under 1 year were hospitalized for the diagnosis of SSSS in the study period. The group included 177 girls and 222 boys. M:F ratio was 1.25:1. The average incidence of SSSS in the Czech Republic was 25.11 cases per 100,000 children under 1 year of age. The highest recorded incidence in the followed period was in 1994, when a total of 57 cases of SSSS was reported, namely 53.47 per 100,000 children. By contrast, in 2003, there were reported only 12 cases and the incidence of 12.81 per 100,000 children. The average length of hospitalization was 6.39 days. In 1995, the highest average length of hospitalization was reported, which was 8.1 days, and then in 2007, the lowest average length of hospitalization, 4.4 days. There was no significant difference in the length of hospitalization in boys and girls. None of the 399 children in the population died. CONCLUSION: In our retrospective study, we established basic epidemiological characteristics of a group of children aged under 1 year with diagnosis of SSSS. As epidemiological data show, the occurrence of this syndrome is not sporadic, but steady. PMID- 22035885 TI - Changing pattern of fungal infection in burn patients. AB - Invasive fungal burn wound infection is an important emerging cause of late onset morbidity and high mortality in patients with major burns. Following a pilot study done in our unit in 1 year, i.e. January 2008-March 2009 in 71 patients where 28% (20 patients) of the burn wound biopsies from suspected cases showed fungal wound invasion (FWI), a detailed study was planned in order to study the epidemiology of fungal infection in burns in our unit wherein routine wound biopsies in 100 patients were sent on 7th, 14th and 21st postburn day over a one year period (July 2009-June 2010). 12 patients (12%) were diagnosed with FWI on culture. This was then followed by another study in a 9 month period (July 2010 March 2011) when wound samples for only 36 patients in whom there was clinical suspicion of fungal infection were sent. 16 of these patients were diagnosed with fungal wound invasion (FWI) thus establishing an incidence of 44% from suspected cases. These studies showing the increase in fungal infection in our unit have therefore made us wiser, increased our awareness and our accuracy in diagnosing this uncommon infection in extensive burns where patient is not only severely immunocompromised but also has many other risk factors making them more vulnerable to fungal invasion. Another glaring fact which emerged from these studies was the rising incidence of nonalbicans Candida infection compared to Candida albicans, especially C. tropicalis and C. krusei which are more severe in nature and associated with a higher mortality. This signifies that there is a shift of FWI in burns from commensal organism, i.e. C. albicans to pathogenic nosocomial organisms, i.e. C. nonalbicans. PMID- 22035886 TI - The severity of kettle burns and the dangers of the dangling cord. AB - Kettle scalds are a major cause of paediatric burn injury. Whilst preventative measures have been advocated for years, the incidence of this type of injury is increasing. Information is lacking regarding severity and mechanism of injury. We prospectively analysed all paediatric scald injuries that warranted referral to a tertiary burn centre to quantify severity, outcome, look into how these burns occurred with a view to providing information for preventative strategies and audited the safety features of 19 top selling kettles. A total of 119 kettle burns were included in the study. Mean age at time of injury was 2 years 1 month (5 months to 12 years). Mean TBSA was 11.8% (2-30) and 62% sustained TBSA >10%. Mean length of stay was 10.4 (1-120) days and a surgical procedure was required in 62% of all kettle scalds. Grafting was undertaken in 52% of patients. Mean number of surgical procedures was 1.7 (median 1, range 1-9). Pulling the kettle cord was the main mechanism of injury (74% vs. 37%). "Cord-pullers" were also significantly younger (mean 20 months vs. 51 months, p<0.05) and underwent significantly more grafting in "cosmetically sensitive" areas (69% vs. 23%, p<0.05). 4 cases of inhalational injury occurred as a result of pulling the kettle cord. Mean kettle cord length was 66 cm (range 45-80) with only 30% employing a coil tidy feature. In view of these findings we discuss current legislative policy on kettle cord length and report on the current safety of today's kettles. Areas for future prevention are discussed. PMID- 22035888 TI - Almanac 2011: stable coronary artery disease. The national society journals present selected research that has driven recent advances in clinical cardiology. PMID- 22035887 TI - Feet burning: a traditional medical practice associated with significant burns in patients with seizures: 4 case reports. PMID- 22035889 TI - Dietary polyphenols as antioxidants and anticancer agents: more questions than answers. AB - High intake of fruit and vegetables is believed to be beneficial to human health. Fruit, vegetables and some beverages, such as tea and coffee, are particularly rich in dietary polyphenols. Various studies have suggested (but not proven) that dietary polyphenols may protect against cardiovasucalar diseases, neurodegenerative diseases and some forms of cancer. Dietary polyphenols may exert their anticancer effects through several possible mechanisms, such as removal of carcinogenic agents, modulation of cancer cell signaling and antioxidant enzymatic activities, and induction of apoptosis as well as cell cycle arrest. Some of these effects may be related, at least partly, to their antioxidant activities. In recent years, a new concept of the antioxidant effects of dietary polyphenols has emerged, i.e., direct scavenging activity toward reactive species and indirect antioxidant activity; the latter activity is thought to arise primarily via the activation of nuclear factor-erythroid-2 related factor 2 which stimulates the activities of antioxidant enzymes such as glutathione peroxidase (GPx), glutathione S-transferase, catalase, NAD(P)H: quinone oxidoreductase-1 (NQO1), and/or phase II enzymes. The direct antioxidant activity of dietary polyphenols in vivo is probably limited because of their low concentrations in vivo, except in the gastrointestinal tract where they are present in high concentrations. Paradoxically, the pro-oxidant effect of dietary polyphenols may contribute to the activation of antioxidant enzymes and protective proteins in cultured cells and animal models because of the adaptation of cells and tissues to mild/moderate oxidative stress. Despite a plethora of in vitro studies on dietary polyphenols, many questions remain to be answered, such as: (1) How relevant are the direct and indirect antioxidant activities of dietary polyphenols in vivo? (2) How important are these activities in the anticancer effects of dietary polyphenols? (3) Do the pro-oxidant effects of dietary polyphenols observed in vitro have any relevance in vivo, especially in the potential anticancer effect of dietary polyphenols? Apparently, more carefully-designed in vivo studies are needed to answer these questions. PMID- 22035890 TI - Fluoroquinolone-associated tendinopathy. AB - The fluoroquinolones (FQs) are used to treat a wide range of infections because of their excellent gastrointestinal absorption, superior tissue penetration and broad-spectrum activity. Recently, FQ-associated tendinopathy and tendon rupture have been reported, especially in the elderly and patients with diabetes and renal failure. However, these adverse effects do not appear to be widely known among physicians. Because of the frequent use of FQs in clinical practice, physicians should be aware of their potential for severe disability from tendon rupture. Achilles tendinopathy or rupture is among the most serious side effects associated with FQ use, with reports markedly increasing, especially with the use of ciprofloxacin. The histopathologic findings include degenerative lesions, fissures, interstitial edema without cellular infiltration, necrosis and neovascularization. There are possible molecular mechanisms accounting for FQ associated tendinopathy. First, ciprofloxacin mediates inhibition of cell proliferation and G2/M cell cycle arrest in tendon cells by down-regulation of cyclin B and cyclin-dependent kinase 1. Second, ciprofloxacin inhibits the spead and migration of tenocytes by down-regulation of focal adhesion kinase phosphorylation. Third, ciprofloxacin enhances the enzymatic activity of matrix metalloproteinase-2 with degradation of type I collagen. Management of FQ associated tendinopathy includes immediate discontinuation of FQs, rest, non steroidal anti-inflammatory drugs, physical modalities and eccentric strengthening exercise. Tendon rupture may require surgical intervention. PMID- 22035891 TI - EMR2 receptor ligation modulates cytokine secretion profiles and cell survival of lipopolysaccharide-treated neutrophils. AB - BACKGROUND: Epidermal growth factor (EGF)-like module-containing mucin-like hormone receptor-like 2 (EMR2) is an adhesion G protein-coupled receptor previously shown to potentiate neutrophil responses to a number of inflammatory stimuli. EMR2 activation promotes neutrophil adhesion and migration, and augments production of reactive oxygen species and degranulation. In this study, we examined the effect of EMR2 ligation by its specific antibody on the cytokine expression profile and cell survival of lipopolysaccharide (LPS)-treated neutrophils. METHODS: Neutrophils were treated with LPS in the absence or presence of the anti-EMR2 mAb, 2A1. Cell apoptosis was determined by flow cytometry analysis using annexin-V and propidium iodide staining. Cell supernatants were collected for the detection of cytokine secretion by enzyme linked immunosorbent assay. RESULTS: We confirmed the specific priming effect of EMR2 on the response of neutrophils to formyl-Met-Leu-Phe by measuring the production of reactive oxygen species. Furthermore, we showed that EMR2 ligation suppresses LPS-induced neutrophil survival. In addition, we demonstrated that ligation of EMR2 changes the secretion profiles of multiple cytokines, including interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1. Finally, higher levels of EMR2 were detected on neutrophils of liver cirrhosis patients and were correlated to a pro-apoptotic phenotype. CONCLUSION: Collectively, the present data indicate a functional role for EMR2 in the modulation of neutrophil activation during inflammation. PMID- 22035892 TI - Biochemotherapy with carmustine, cisplatin, dacarbazine, tamoxifen and low-dose interleukin-2 for patients with metastatic malignant melanoma. AB - BACKGROUND: The toxicity and efficacy of biochemotherapy with low-dose interleukin-2 for patients with metastatic malignant melanoma (MM) were studied. METHOD: Metastatic chemo-naive MM patients were given biochemotherapy (BCDT regimen) with carmustine (BCNU), cisplatin (CDDP), dacarbazine (DTIC), and tamoxifen and interleukin-2 (IL-2) 18 Million International Units in divided doses by subcutaneous injection three times a week for four weeks. BCDT consisted of BCNU (150 mg/m2, day l every 8 weeks), CDDP (25 mg/m2, days l-3 every 4 weeks), DTIC (220 mg/m2, days 1-3 every 4 weeks) and tamoxifen 10 mg twice a day. Treatment was repeated for a total of 6 cycles, or until disease progression or unbearable toxicity. RESULTS: From Nov 2001 to July 2005, 40 patients (20 men; 20 women) were enrolled. Their median age was 54 years (range 22-79 years). Subtypes of melanoma included 23 (57.5%) acral lentiginous, 11 (27.5%) nodular, 1 (2.5%) mucosal, and 5 (12.5%) others. Grade 3-4 toxicities included neutropenia (27.5%), anemia (45%), and thrombocytopenia (40%). Constitutional IL-2 toxicities included indurate injection site (57.5%), fever (60%), chills (55%), itchy skin (42.5%), bone pain (32.5%) and myalgia (45%). Grade 1-2 hypotension was noted in 12.5% of patients. Eosinophilia (range 5% to 71%) was evident in 72.5% of patients. The response rate was 32.5% including 5% with a complete response, 27.5% with a partial response, and 17.5% with stable disease. The median progression-free survival was 6.2 months (95% CI: 2.9~9.6 months). The median overall survival was 11.3 months (95% CI: 7.0~15.6 months). Five patients (12.5%) who presented with oligo-metastasis achieved five-year survivals. CONCLUSIONS: Our data demonstrated that low-dose IL-2 plus BCDT is tolerable. A durable response and long-term survival can be achieved in a small subgroup of patients. PMID- 22035893 TI - Serum HCV RNA level is not associated with insulin resistance and metabolic syndrome in chronic hepatitis C patients with genotype 1 or 2 infection. AB - BACKGROUND: Previous reports have indicated that insulin resistance (IR) is associated with chronic hepatits C virus (HCV) infection. However, the correlations between IR, metabolic syndrome (MS), and serum HCV RNA levels are still controversial. The aim of this study was to determine the relationships between IR, MS, and HCV RNA in patients with chronic genotype 1 or 2 HCV infection. METHODS: One hundred and twenty subjects with chronic genotype 1 or 2 HCV infection with complete clinical data were prospectively enrolled. Baseline and laboratory data were collected and analyzed. IR was defined as a homeostatic model assessment- IR (HOMA-IR) score > 2.5. RESULTS: Of the 120 patients, 47 (39.2%) had a HOMA-IR > 2.5, and 42 (35%) met the criteria for MS. IR was significantly associated with a high body mass index (p < 0.0001), high waist circumference (p < 0.0001) and high triglyceride level (p = 0.025). IR was an independent predictor of MS. However, in multivariate linear regression analysis, the serum HCV RNA level was not significantly different in chronic hepatitis C patients with or without IR (p = 0.761), and with or without MS (p = 0.292). CONCLUSIONS: IR and MS are not uncommon in patients with chronic hepatitis C. The serum HCV RNA level is not associated with the presence of IR or MS in chronic hepatitis C patients with genotype 1 or 2 infection. The impact of hepatitis C virus on IR is not dose responsive. PMID- 22035894 TI - Does adequate bladder cuff excision impact outcomes in patients undergoing nephroureterectomy for upper tract urothelial carcinoma. AB - BACKGROUND: Nephroureterectomy with bladder cuff excision has been the gold standard surgical treatment for upper tract urothelial carcinoma. In this study, we determined the independent prognostic factors for upper tract urothelial carcinoma. METHODS: The records of 285 consecutive patients undergoing nephroureterectomy with bladder cuff excision at our institution between 2003 and 2007 were reviewed. Kaplan-Meier survival curves were used to determine the 5 year cancer-specific survival rates for all patient groups. Cox proportional hazard regression was performed to determine the factors that had an independent impact on the survival of patients with upper tract urothelial carcinoma. RESULTS: A total of 192 patients matching the inclusion criteria were enrolled in our study. The mean follow-up time was 43.81 months. We found that the female gender, a lower ureter free of invasion, and an adequate bladder cuff excision were independent factors for a better tumor recurrence-free survival rate. The pathology stage and recurrence (none, intravesical or extravesical) were independent factors for the overall survival rate. A non-adequate ureterectomy including the bladder cuff was associated with a high body mass index (BMI) and the infiltrating tumor pattern of urothelial carcinoma. CONCLUSION: Nnephroureterectomy together with adequate bladder cuff excision plays an extremely important role in the surgical treatment of upper urinary tract urothelial carcinoma. Patients with incomplete resections of the bladder cuff are at increased risk of tumor recurrence. PMID- 22035895 TI - Is a biopsy necessary for colon polyps suitable for polypectomy when performing a colonoscopy? AB - BACKGROUND: The incidence of colorectal cancer is increasing in Taiwan. Adenomatous polyps are known to be precancerous lesions and need to be removed. New techniques like chromendoscopy, magnifying endoscopy, narrow band imaging and magnifying endoscopy with flexible spectral imaging color enhancement may improve the accuracy of identifying precancerous polyps but are not widely available in the real world. This study analyzed the conventional biopsy method in diagnosing early colon cancer and the necessity for subsequent surgery after polypectomy. METHODS: From January 2002 to December 2007, 1027 adenomatous polypoid specimens taken from 720 patients who received polypectomy by conventional white light colonoscopy were studied. The pathologic reports of 26 specimens of early cancer or high grade dysplasia from 25 patients were analyzed. Protruding polyps were classified as pedunculated (o-Ip), subpedunculated (o-Isp) and sessile (o-Is). RESULTS: Fourteen of the 26 specimens were type o-Ip, 10 were type o-Isp, and 2 were type o-Is. The pathologic reports were high grade dysplasia (n = 5), mucosal adenocarcinoma (n = 18) and submucosal adenocarcinoma (n = 3). Among these, 7 lesions from 7 patients received a randomized biopsy instead of immediate polypectomy. Adenoma was reported in 6 of them with only one malignancy detected (false negative rate: 86%). Eight patients received surgery. The mean follow-up period for these patients was 17 months, and none of them had recurrences. CONCLUSIONS: The randomized biopsy method for adenomatous polyps has a high false negative rate for early colon cancer and high grade dysplasia and is therefore not necessary in cases of protruding type polyps which can be removed by polypectomy. An adequate direct polypectomy may completely remove the protruding type of early colon cancer. PMID- 22035896 TI - Complications of hip fractures in children. AB - BACKGROUND: Hip fractures account for < 1% of all pediatric fractures. Most are caused by a high-energy mechanism. Complications occur at a high rate because the vascular and osseous anatomy of the child's proximal femur is vulnerable to injury. The purposes of this study were to evaluate whether osteonecrosis influences the functional results and to analyze the risk factors for the development of osteonecrosis. METHODS: We conducted a retrospective review of the complications of hip fractures (3 transepiphyseal fractures, 13 transcervical fractures, 6 cervico-trochanteric fractures, and 1 intertrochanteric fracture) in 23 patients (15 boys and 8 girls) between January 1988 and December 1997. Most injuries were caused by falling from a height or a motorcycle accident. The medical records and serial radiographs of all patients were reviewed. The function of the injured site was evaluated using Ratliff's criteria. RESULTS: The ages of these children at the time of injury ranged from 1.5 to 16 years (average 11.1 years). The mean follow-up was 4.91 years (range, 1 year to 12 years and 7 months). Overall, complications included osteonecrosis in 11 (48%) patients, premature physeal closure in 11 (48%), coxa vara in 3 (13%) and coxa valga in 2 (9%). There was no nonunion. Poor outcomes were related to the development of osteonecrosis. The time to surgery (<= 12 hours) and the quality of reduction significantly influenced the occurrence of osteonecrosis. The occurrence and severity of femoral head osteonecrosis significantly influenced the functional results (p < 0.001, and p < 0.048, respectively). CONCLUSION: Osteonecrosis is the most severe complication after hip fractures in children and is associated with poor functional results. The time to surgery and the quality of reduction were the significant predictors in our study. PMID- 22035897 TI - Predictors of outcome after open repair of ruptured abdominal aortic aneurysms. AB - BACKGROUND: To determine predictors associated with early hospital death, 30-day mortality, and long-term survival after open surgical treatment of ruptured abdominal aortic aneurysms (RAAAs). METHODS: A retrospective chart review of 127 consecutive patients who received open surgical treatment of a RAAA at Chang Gung Memorial Hospital, Taiwan, from February 1994 to May 2007. Data recorded included patient characteristics, medical history, perioperative variables, and outcomes. RESULTS: There were 104 men and 23 women with a mean age of 70 ? 12 years in the analysis. Patients with RAAAs were classified into two groups; 100 (78.7%) patients were classified as group I (hemodynamically stable), and 27 (21.3%) patients were classified as group II (hemodynamically unstable at arrival). The 30-day mortality was 22% for group I and 74.1% for group II. Multivariate analysis identified age > 75 years old (odds ratio [OR], 0.083; 95% confidence interval [CI] 0.02-0.36), hemodynamically unstable state (OR, 0.081; 95% CI 0.016 0.4), blood transfusion > 5 L (OR, 0.14; 95% CI 0.038-0.54), intraperitoneal rupture (OR, 7.2; 95% CI 1.4-36), urine output < 0.5 mL/kg/min (OR, 22; 95% CI 4.6-110), and suprarenal cross-clamping (OR, 0.083; 95% CI 0.019-0.36) as incremental risk factors for 30-day mortality. CONCLUSION: Significant predictors of mortality in patients with RAAAs include hemodynamically unstable state, age > 75 years old, intraperitoneal rupture, low intraoperative urine output, and suprarenal cross-clamping. PMID- 22035898 TI - the impact of personality on depression among university students in Taiwan. AB - BACKGROUND: Depression in Taiwanese university students is a significant problem in terms of life and financial costs. The purpose of this study was to examine the impact of four selected personality traits, namely interpersonal problems, ideas of being persecuted, social students in introversion, and self depreciation, on the inclination to be depressed among students in Taiwanese university. METHODS: A self-report survey was administered to students at a Taiwanese university and consisted of three parts: demographics, the Chinese version of the Basic Personality Inventory (BPI), and the Taiwanese Depression Questionnaire. The level of depression among students was assessed, and the relationships among the various variables were explored using analysis of variance (ANOVA) and regression. RESULTS: Altogether, 255 students successfully completed the survey. Overall, 37.62% of students were suffering from depression, including 4.7% who indicated that they were severely depressed, 18.30% who were moderately depressed, and 14% who were mildly depressed. In a multiple-regression model, ideas of being persecuted and self depreciation were both significant when predicting an inclination to be depressed. CONCLUSION: Depression is a problem for many university students in Taiwan. Understanding which personality traits are related to depression in Taiwanese students is important for student affair administrators and medical professionals and will help them to prevent and treat this debilitating illness. PMID- 22035899 TI - Amisulpride and neuroleptic malignant syndrome. AB - Neuroleptic malignant syndrome (NMS) is a rare but lethal complication of neuroleptics. Its incidence ranges between 0.02% and 3%. Amisulpride, a second generation neuroleptic, was associated with rhabdomyolysis in one report and NMS in 2 reports. Although the precise pathogenesis is still unclear, dopamine receptor blockade is theorized to play a central role. Conventional presentations include hyperthermia, muscle rigidity, and elevated creatine kinase concentrations. However, similar to other second generation neuroleptics, amisulpride induces an atypical form of NMS, which presents with lower degrees of hyperthermia and elevation of creatine kinase than the typical form. This phenomenon makes it difficult to identify early signs of NMS. This study describes the first case of amisulprideinduced NMS in Taiwan, together with a review of the current knowledge on NMS. In this case, the correlation between NMS and amisulpride was categorized as "probable" on the Naranjo adverse drug reaction probability scale. PMID- 22035900 TI - Ruptured aneurysm of the accessory middle cerebral artery associated with moyamoya disease: a case report. AB - The accessory middle cerebral artery can provide collateral blood supply in moyamoya disease. We report a case of unilateral moyamoya disease which demonstrates the anatomy of the right accessory middle cerebral artery and a ruptured peripheral aneurysm on the artery. Our patient was a 56-year-old woman who initially suffered from headache and lethargy. Right caudate nucleus hemorrhage with intraventricular extension and spontaneous subarachnoid hemorrhage were found on brain computed tomography. A ruptured peripheral accessory middle cerebral artery aneurysm associated with unilateral moyamoya disease was diagnosed on cerebral angiography. Surgical intervention to excise the peripheral accessory middle cerebral artery aneurysm assisted by frameless navigation guidance to reduce the risk of damage to collateral vessels was done successfully. Histopathology of excised tissue showed this anomaly was a pseudoaneurysm. The management of an aneurysm in moyamoya disease should be modified based on its location and collateral vessels. Prevention of aneurysm bleeding and preservation of collateral vessels during craniotomy are the critical when managing hemorrhagic moyamoya disease. This case suggests that surgical intervention for ruptured intracranial aneurysms is safe with the use of frameless navigation guidance to minimize collateral vessel injuries. PMID- 22035901 TI - Innervation of the inferior oblique muscle: anatomical facts. PMID- 22035902 TI - Antimony leaching from MSWI bottom ash: modelling of the effect of pH and carbonation. AB - Development of treatment methods to reduce Sb leaching from municipal solid waste incinerator (MSWI) bottom ash, such as accelerated carbonation, is being complicated by insufficient understanding of Sb geochemistry. The leaching of antimonate (Sb(V)) and antimonite (Sb(III)) in MSWI bottom was studied as a function of pH and degree of carbonation. While total (Sb(V)+Sb(III)) leaching was lowest (1.2 mg kg(-1)) at the natural pH (i.e. 10.6) of uncarbonated bottom ash, HPLC-ICP-MS analysis showed that acidification and carbonation increased Sb(V) leaching, but decreased Sb(III) leaching, probably because Sb(III)(OH)(4)( ) became less stable. PHREEQC geochemical modelling suggested that Sb(V) concentrations approached equilibrium with the romeites, i.e. calcium antimonates, Ca(1.13)Sb(2)(OH)(0.26).0.74H(2)O at pH=10.6 and Ca[Sb(OH)(6)](2) at pH=8. It is hypothesised that not interaction with ettringite but dissolution of romeite controls antimonate leaching in the pH range 8-11 in MSWI bottom ash, because while Ca is preferentially leached from romeite, the mineral structures containing more Ca at higher pH are less soluble. A model was proposed where acidification and carbonation both lead to lower Ca(2+) and/or hydroxyl concentration, which removes Ca(2+) and hydroxyls from the romeite structure and leads to comparably higher Sb(V) concentration in equilibrium with romeite. Sb solubility depends on pH and Ca(2+) availability in this model, which has implications for bottom ash valorisation and risk assessment. PMID- 22035903 TI - Process and technological aspects of municipal solid waste gasification. A review. AB - The paper proposes a critical assessment of municipal solid waste gasification today, starting from basic aspects of the process (process types and steps, operating and performance parameters) and arriving to a comparative analysis of the reactors (fixed bed, fluidized bed, entrained bed, vertical shaft, moving grate furnace, rotary kiln, plasma reactor) as well as of the possible plant configurations (heat gasifier and power gasifier) and the environmental performances of the main commercially available gasifiers for municipal solid wastes. The analysis indicates that gasification is a technically viable option for the solid waste conversion, including residual waste from separate collection of municipal solid waste. It is able to meet existing emission limits and can have a remarkable effect on reduction of landfill disposal option. PMID- 22035904 TI - Genomics of common diseases: approaching the tipping point. AB - A report on the Wellcome Trust Scientific Conference 'The Genomics of Common Diseases 2011', held at the Wellcome Trust Conference Centre, Hinxton, Cambridge, UK, 30 August to 2 September 2011. PMID- 22035905 TI - A novel neutrophil derived inflammatory biomarker of pulmonary exacerbation in cystic fibrosis. AB - BACKGROUND: The focus of this study was to characterize a novel biomarker for cystic fibrosis (CF) that could reflect exacerbations of the disease and could be useful for therapeutic stratification of patients, or for testing of potential drug treatments. This study focused exclusively on a protein complex containing alpha-1 antitrypsin and CD16b (AAT:CD16b) which is released into the bloodstream from membranes of pro-inflammatory primed neutrophils. METHODS: Neutrophil membrane expression and extracellular levels of AAT and CD16b were quantified by flow cytometry, Western blot analysis and by 2D-PAGE. Interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and AAT:CD16b complex were quantified in CF plasma (n=38), samples post antibiotic treatment for 14 days (n=10), chronic obstructive pulmonary disease (n=10), AAT deficient (n=10) and healthy control (n=14) plasma samples by ELISA. RESULTS: Cell priming with IL-8 and TNF-alpha caused release of the AAT:CD16b complex from the neutrophil cell membrane. Circulating plasma levels of IL-8, TNF-alpha and AAT:CD16b complex were significantly higher in patients with CF than in the other patient groups or healthy controls (P<0.05). Antibiotic treatment of pulmonary exacerbation in patients with CF led to decreased plasma protein concentrations of AAT:CD16b complex with a significant correlation with improved FEV1 (r=0.81, P=0.003). CONCLUSION: The results of this study have shown that levels of AAT:CD16b complex present in plasma correlate to the inflammatory status of patients. The AAT:CD16b biomarker may become a useful addition to the clinical diagnosis of exacerbations in CF. PMID- 22035906 TI - [The role and method of fluorescence-guided cystoscopy in 2011 for management of bladder cancer: Review of the Oncology Committee of the French Urology Association]. AB - AIM: Fluorescence-guided cystoscopy is a useful tool for bladder tumour detection in association with white-light cystoscopy and decreases the residual tumour rate. The aim of the study was to provide an overview of the pertinent literature on this subject. MATERIALS AND METHODS: The data were provide from a Medline((r)) research by using the follow keywords: urinary bladder neoplasms; cystoscopy; fluorescence; prognosis; intraepithelial neoplasm. RESULTS: No evidence 1 level data was available. The fluorescence-guided cystoscopy improves the bladder cancer detection rate, especially the flat lesions, and improve the recurrence free survival by decreasing the residual tumour rate. The specific indications for fluorescence-guided cystoscopy in the diagnosis and management of non-muscle invasive bladder cancer (NMIBC) should benefit the patients. CONCLUSION: The fluorescence-guided cystoscopy is a benefical tool in association with white light cystoscopy in NMIBC diagnosis. It has been shown to have a positive impact on recurrence-free survival but not on progression-free survival. More investigations with significant follow-up should be lead in the future to accurately assess its therapeutic impact on patients. PMID- 22035908 TI - [Cell therapy and urinary incontinence: if far, so close]. PMID- 22035907 TI - [Prevention of complications of general anesthesia linked with laparoscopic access and with robot-assisted radical prostatectomy]. AB - INTRODUCTION: The aim of our work was to present a review of technical features and complications of general anesthesia during robot-assisted laparoscopic radical prostatectomy (RALRP). MATERIALS AND METHODS: Data on RALRP and general anesthesia were explored on Medline using the following MeSH terms: radical prostatectomy; morbidity; anesthesia complications; laparoscopy; robotics; Trendeleburg. Publications were considered on the following criteria: methodology, relevance and date of publication. RESULTS: There was no data of level of evidence 1 available. The first RALRP was reported in 2000. Technological innovation brought by the robot with its 3-D vision, the acquisition of degrees of mobility and a more ergonomic position for the surgeon, have led to a growing interest from new teams in the western world. However, the RALRP generates constraints for the anesthesia team who need to incorporate the rules of laparoscopy and the patient's specific installation to guarantee maximum safety. There are inherent complications with the installation of the patient himself in the Trendelenburg position (ocular, neurological, hemodynamic, respiratory) and respiratory complications related to the specific procedure in gaseous atmosphere due to pneumoperitoneum. One of the criteria of the quality of publications in the field of surgery is related to the objective evaluation of complications by appropriate scale systems and the complications of general anesthesia must also be absolutely recorded. CONCLUSION: RALRP had deeply modified the anatomical landmarks of the surgical removal of prostate cancer. However, the perioperative environment has also been completely altered and the installation of RALRP in the daily routine of a service requires from the anesthesia team to adapt their behavior to this sophisticated surgical access. PMID- 22035909 TI - [Renal angiomyolipomas without fat component: tomodensitometric and histologic characteristics, clinical course]. AB - INTRODUCTION: Angiomyolipoma is the most frequent benign renal solid tumor. Because of the lack of fat component on the CT scan, diagnosis of this tumor is hard and can require percutaneous biopsy of unknown renal tumor. The follow-up of the poor fat CT scan component AML (PFCT AML) is uncertain. METHODS: Five hundred percutaneous renal biopsy under tomodenstitometry have been realised between 1998 and 2008. There was 41 PFCT AML on the 500 biopsy. By definition, a PFCT AML is an AML where the diagnosis is done on a percutaneous biopsy but where there was no fat component on the first CT scan. We studied and compared clinical, tomodensitometric and histologic parameters of these 41 patients (mean age: 56, 9+/-11.04; sexe rate M/F: 6/35) where renal AML was diagnosed on percutaneous renal biopsy but without fat component on CT scan. Average size was 26.44+/ 14.68mm. We phone-called 16 patients for the long-term follow-up. Average follow up was 41+/-28.3 months. For four patients on 16, initial diagnosis was done in front of local symptoms, for one of the 16 diagnosis was done in front of general symptoms, for one of the diagnosis was done during Bourneville tuberous sclerosis evolution and 10 of the 16 was done fortuitously. RESULTS: After review of the initial CT scan, fat density was found on 24% of them. Ten percent was epithelioid angiomyolipoma. Four renal biopsy on 41 (10%) was epithelioid AML. No epithelioid AML had fat component after the second look of the CT scan. Among the 16 patients who were phone-called, three (19%) underwent a complication. Two had abdominal pain and was treated medically. Initial sizes were 26 and 30mm. Only one patient must be operated by radical nephrectomy for acute hemorrhage. Initial size was 45mm. No neoplasic degeneration was identified for those 16 patients. CONCLUSION: In our study, the PFCT AML rate was 8.2%. In 25% cases, CT scan read through shown a fat component and could help for the diagnosis. PFCT AML evolution seems to be the same as a classic AML. Conservative treatment had a good covering because there was no death and no malignant evolution. However, we found 10% of epithelioid angiomyolipoma in which malignant risk is high. PFCT AML diagnosed on renal percutaneous biopsy of unknown renal tumor requires the same management than the classic AML. PMID- 22035910 TI - [Nephron-sparing surgery is superior to radical nephrectomy in preserving renal function outcome in tumors larger than 4 cm]. AB - OBJECTIVE: The objective of the present study was to analyse whether nephron sparing surgery (NSS) was superior to radical nephrectomy (RN) in preserving renal function outcome in tumors larger than 4cm. METHODS: The data from 888 patients who had been operated upon at eight french university hospitals were retrospectively analyzed. Glomerular filtration rate (GFR) pre- and post-surgery was calculated with the abbreviated Modification of Diet in Renal Disease (MDRD) equation. For a fair comparison between the two techniques, all imperative indications for NSS and all GFR<30 mL/min/1.73 m(2) were excluded from analysis. A shift to a less favorable DFG group following surgery was considered clinically significant. RESULTS: Seven hundred and thirty patients were suitable for comparison. Median age at diagnosis was 60 years (19-88). Tumors measuring more than 4cm represented 359 (49.2%) cases. NSS and RN were performed in 384 (52.6%) and 346 (47.4%) patients, respectively. In univariate analysis, patients undergoing NSS had a smaller risk than RN of developing significant GFR change following surgery. This was true for tumors<=4cm (P=0.0001) and for tumors>4cm (P=0.018). In multivariate analysis, the following criteria were independent predictive factors for developing significant postoperative GFR loss: the use of RN (P=0.001), decreased preoperative DFG (P=0.006), increased age at diagnosis (P=0.001) and increased ASA score (P=0.004). CONCLUSION: The renal function benefit offered by elective NSS over RN persists even when expanding NSS indications beyond the traditional 4 cm cut-off. PMID- 22035911 TI - [The neutrophil gelatinase-associated lipocalin, or LCN 2, marker of aggressiveness in clear cell renal cell carcinoma]. AB - OBJECTIVE: To determine the prognostic significance of the neutrophil gelatinase associated lipocalin (NGAL) and the matrix metalloproteinase 9 (MMP-9) in clear cell renal cell carcinoma (CCRCC). PATIENTS AND METHODS: NGAL and MMP-9 expression were quantified by immunohistochemistry in clear renal cell carcinoma tissues and in sera by Enzyme Linked Immunosorbent Assay (Elisa). Results were associated with clinicopathologic data. RESULTS: Seventy-four patients operated for CCRCC in Rennes between 2003 and 2009 were included. High concentrations of NGAL-MMP-9 complex in serum were associated with short progression free survival (PFS) (33.3 months versus 47.3 months, P=0.016) and poor overall survival (42.5 months versus 51.9 months, P<0.047). High NGAL concentrations in serum were also associated with shorter PFS (13.6 months versus 41.6 months, P=0.04). However, no NGAL expression was observed in renal tumor cells. Interestingly, NGAL was expressed by neutrophils infiltrating CCRCC and we showed that the density of NGAL expressing neutrophils was associated with pejorative PFS and survival (36.9months versus 56.1 months, P<0.006). CONCLUSION: In this study, we showed the pejorative significance of NGAL-MMP-9 complex and NGAL rates in serum of CCRCC. We also confirmed that density of NGAL expressing neutrophils in CCRCC was associated with poor outcome. PMID- 22035912 TI - [Prospective evaluation of intrasphincteric injections of autologous muscular cells in patients with stress urinary incontinence following radical prostatectomy]. AB - PURPOSE: Cell therapy for urinary incontinence management has been experienced in animals with encouraging results, but studies in human beings are lacking. Our primary objective was to assess the safety of intrasphincteric injections of autologous muscular cells in patients with postprostatectomy incontinence (PPI). Secondary objectives focused on complications efficacy. METHODS: We conducted an open, prospective study in a single center on 12 patients presenting PPI. Patients underwent intrasphincteric injections of autologous muscular cells isolated from a biopsy of deltoid muscle. The primary endpoint was the Q(max) variation at the three month visit in order to assess potential bladder outlet obstruction. Secondary endpoints assessed side effects and efficacy parameters based on symptoms, quality of life score, voiding diary, pad-test, and urethral pressure profile at one, two, three, six and 12 months after injection. RESULTS: No immediate complication occurred and no significant variation was noted on Q(max). The only side effects possibly product-related were three cases of urinary tract infection treated by antibiotics. An acceptable safety and tolerability of the procedure whatever the injected dose of muscular cells was demonstrated. Results on efficacy after one year were heterogeneous, with 4/12 patients describing reduced urine leakage episodes, 1/12 patient presenting increased maximal closure pressure, and 8/12 patients showing improvement on pad test. CONCLUSIONS: Cell therapy consisting of intrasphincteric injections of autologous muscular cells in patients with PPI was a feasible and safe procedure. The results point out that some subjects may positively respond to this procedure, but clinical efficacy remains to be confirmed. PMID- 22035913 TI - [The role of a 6-month depot form of hormone therapy in the treatment of advanced hormone-dependent prostate cancer: Results from the 'ELIRE' observational study]. AB - OBJECTIVES: Androgen-deprivation therapy modalities are on continuing evolution. Leuprolide Acetate (LA) Eligard((r))45mg was the first 6-monthly LHRH agonist (agoniste luteinizing hormone-releasing hormone [LHRHa]) treatment available for use in prostate cancer. The objective of this study was to assess the use of the 3-monthly and the 6-monthly LHRHa in patients with prostate cancer. PATIENTS AND METHODS: A two-step survey (registration and follow-up) was held between July 2008 and January 2009. One hundred and sixty doctors included patients treated with LHRHa for prostate cancer. Then, a follow-up registry was implemented for patients who had been prescribed a 3- or 6-monthly LHRHa. RESULTS: Data analysis showed that the 1853 registered patients had a mean age of 75 years old. Time to diagnosis was 7 months. Among them, 26.4% had an N+ and/or M+ cancer. The most tumor node metastasis (TNM) stage represented was T3N0M0 with Gleason score 7. High prostate specific antigen (PSA) level and metastatic stage were the main motives for LHRHa prescription. Choice criteria for a 3 or a 6-monthly LHRHa were patient autonomy (3.2 vs 18.4%), age (27.2 vs 44%) and anxiety (28 vs 16.8%). Patients for 6-monthly LHRHa were likely to be with low urinary symptoms, older, less autonomous and less anxious. The reported advantage of the 3-monthly LHRHa was the high satisfying quality of medical follow-up. For the 6-monthly form, the advantages were the flexibility and the freedom to stop worrying about their cancer for up to 6 months. CONCLUSION: The 6-monthly LHRHa provides more flexibility in the management and follow-up of patients with locally advanced or metastatic prostate cancer. PMID- 22035914 TI - [Urological complications of gynecologic surgery]. AB - OBJECTIVE: To analyze the epidemiological, anatomoclinical, surgical and evolutionary aspects of the urological complications of gynecological surgery. MATERIAL AND METHODS: It was about a retrospective survey, concerning 81 patients hospitalized in the department of urology of the university hospital, Brazzaville from 2000 to 2008 for urological complications of the gynecological surgery. The epidemiological, diagnostic, surgical and evolutionary parameters have been analyzed. RESULTS: The urological complication of the gynecological surgery has been recovered in 3% of patients hospitalized in urology. The middle age was 37+/ 14.52 years (17 and 74 years). The median was about 36 years. The middle delay of diagnosis was 15 days (0 and 350 days). The revealing clinical signs were: the oligoanuria (n=12), the urinary incontinence (n=57), the lumbar pain (n=9) and the cyclic hematuria (n=2). The surgical interventions in reason were: the Caesarean (n=50), the hysterectomy for fibroma (n=26), the myomectomy (n=3) and the hysterectomy for cancer (n=2). Anatomical lesion were 55 (67.9%) vesicovaginal fistulas, 12 (14.8%) ureteral ligatures, eight (10%) uretero vaginal fistulas, three (3.7%) vesico-uterine fistulas, two (2.4%) wounds ureteral and one (1.2%) vaginal vesico-fistulas and uretero-vaginal fistulas. The treatment consisted in one termino-terminal ureterorraphia, 20 uretero-vesical reimplantation, 57 cures of vesico-vaginal fistulas and one nephrectomy. The recovery was obtained at 96% of the ureteral lesions and 90% of the vesico vaginal fistulas. CONCLUSION: The lesions of the ureteral and the bladder were often met during the gynecological surgery. The treatment requires knowledge of the anatomy of pelvis. PMID- 22035915 TI - [Completeness and quality of multidisciplinary team meetings: the example of prostate cancer in the Mid-Pyrenees region]. AB - OBJECTIVES: To determine the completeness of the examination of cancer patient cases in a multidisciplinary team meeting (MDTM), to study the factors that can affect this examination and to assess the quality of the MDTM concerning prostate cancer in Tarn. METHODS: Completeness was estimated by comparing the database of the Tarn cancer registry containing all the inhabitants of this department for whom prostate cancer was diagnosed in 2007 with the list of patients living in Tarn whose cases were discussed during a Midi-Pyrenees MDTM. Determinants of the case discussion in MDTM were studied from data collected in medical records (age, stage at diagnosis, PSA level, Gleason score, treatment). The MDTM quality study (delay in management, whether the case was seen before or after treatment, required elements for MDTM, clinical data, conformity between suggested treatment and guidelines, adequacy between suggested and performed treatments) was based on the MDTM forms retrieved from the DCO and from medical records. RESULTS: Four hundred and fifty-nine patients were re-examined. The pretherapeutic passage rate within three months after diagnosis was 56.2%. The probability of a discussion in MDTM decreased for people over 85 years of age (OR=0.10) compared with the 70-74 year-old people and it increased for the N+M+ (OR=4.23) compared with the T1-T2. Patients for whom radiotherapy was considered were presented more frequently than the others. The MDTM quality was studied based on 220 DCO forms. The patient's physician attended the MDTM in 65% of the cases, 97% of the suggested treatments were consistent with the guidelines and 90% of the performed treatments complied with the suggested treatment. CONCLUSION: The discussion rate in MDTM has not reached the 100% planned by the first "plan cancer" yet, but when a MDTM was carried out, its compliance and adequacy were high. While seniors' cases require interdisciplinarity because of a complicated management, they were less discussed in MDTM. PMID- 22035916 TI - [Right obstructive pyelonephritis due to supra-piriform herniation of the pelvic ureter: a clinical case]. AB - Ureteric herniations are extremely rare. We are reporting the case of a 57-year old female presenting with an upper urinary tract sepsis due to a pelvic ureteral herniation into the supra-piriform sciatic foramen. The diagnosis was made by the CT scan and the treatment was performed in two steps: first the upper urinary tract was drained, and then the hernia was surgically treated. Although ureteral hernias are exceptional causes for nephritic colic, urologists must be aware of the specificity of the diagnosis and of the treatment in order to avoid complications. PMID- 22035917 TI - [Plasmacytoid urothelial carcinoma of the bladder with prostate cancer: report of two cases]. AB - Plasmacytoid urothelial carcinoma (PUC) is a rare variant of urothelial carcinoma with aggressive clinicopathological behaviours. We experienced two cases of PUC of urinary bladder. Both cases were advanced cancer with extravesical invasion and lymph node metastases. They also had coexisting prostatic carcinoma, one was preoperatively diagnosed and the other was incidentally discovered after surgery. As these cases were the first report of PUC simultaneously associated with prostatic carcinoma, clinicopathological features and the treatment options were discussed. PMID- 22035918 TI - The adaptive response of lichens to mercury exposure involves changes in the photosynthetic machinery. AB - Lichens are an excellent model to study the bioaccumulation of heavy metals but limited information is available on the molecular mechanisms occurring during bioaccumulation. We investigated the changes of the lichen proteome during exposure to constant concentrations of mercury. We found that most of changes involves proteins of the photosynthetic pathway, such as the chloroplastic photosystem I reaction center subunit II, the oxygen-evolving protein and the chloroplastic ATP synthase beta-subunit. This suggests that photosynthesis is a target of the toxic effects of mercury. These findings are also supported by changes in the content of photosynthetic pigments (chlorophyll a and b, and beta carotene). Alterations to the photosynthetic machinery also reflect on the structure of thylakoid membranes of algal cells. Response of lichens to mercury also involves stress-related proteins (such as Hsp70) but not cytoskeletal proteins. Results suggest that lichens adapt to mercury exposure by changing the metabolic production of energy. PMID- 22035919 TI - Detecting diclofenac in livestock carcasses in India with an ELISA: a tool to prevent widespread vulture poisoning. AB - Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), has caused catastrophic vulture declines across the Indian sub-continent. Here, an indirect ELISA is used to detect and quantify diclofenac in 1251 liver samples from livestock carcasses collected across India between August 2007 and June 2008, one to two years after a ban on diclofenac manufacture and distribution for veterinary use was implemented. The ELISAs applicability was authenticated with independent data obtained using LC-ESI/MS. Of 1251 samples, 1150 (91.9%) were negative for diclofenac using both methods, and 60 (4.8%) were positive at 10 4348 and 10-4441 MUg kg(-1) when analysed by ELISA and LC-ESI/MS, respectively. The residue level relationship in the 60 positive samples was highly significant (p < 0.001, r(2) = 0.644). Data suggest that this immunological assay could be used not only for cost effective sample screening, but also for residue level semi-quantification. PMID- 22035920 TI - Microsporidia parasites disrupt the responses to cadmium exposure in a gammarid. AB - Microsporidia parasites are commonly found in amphipods, where they are often asymptomatic, vertically-transmitted and have several effects on host sexuality and behaviour. As amphipods are often used as models in ecotoxicological studies, we investigated the effect of microsporidian infections on energy reserves and defence capacities of Gammarus roeseli under cadmium stress. Only females were infected by two microsporidia parasites: Dictyocoela roeselum or Dictyocoela muelleri. In physiological conditions, microsporidia had no major effect on energy reserves and defence capacities of G. roeseli, while under cadmium exposure, energy reserves and antioxidant defence were weaker in infected females. Moreover, higher malondialdehyde levels detected in infected females revealed that they suffered more cellular damages. Our results suggest that microsporidia may affect gammarid fitness in stressful conditions, when parasitic stress cannot be compensated by the host. Consequently, microsporidia parasites should be a factor necessary to take into account in ecotoxicology studies involving amphipods. PMID- 22035921 TI - Synthetic fertilizer management for China's cereal crops has reduced N2O emissions since the early 2000s. AB - China has implemented a soil testing and fertilizer recommendation (STFR) program to reduce the over-usage of synthetic nitrogen (N) fertilizer on cereal crops since the late 1990 s. Using province scale datasets, we estimated an annual reduction rate of 2.5-5.1 kg N ha(-1) from 1998 to 2008 and improving grain yields, which were attributed to the balanced application of phosphate and potassium fertilization. Relative to the means for 1998-2000, the synthetic N fertilizer input and the corresponding N-induced N(2)O production in cereal crops were reduced by 22 +/- 0.7 Tg N and 241 +/- 4 Gg N(2)O-N in 2001-2008. Further investigation suggested that the N(2)O emission related to wheat and maize cultivation could be reduced by 32-43 Gg N(2)O-N per year in China (26%-41% of the emissions in 2008) if the STFR practice is implemented universally in the future. PMID- 22035922 TI - Gene expression of heat shock protein 70, interleukin-1beta and tumor necrosis factor alpha as tools to identify immunotoxic effects on Xenopus laevis: a dose response study with benzo[a]pyrene and its degradation products. AB - The exposure to benzo[a]pyrene (B[a]P) results in an alteration of immune function in mammals and fish, and the analysis of cytokine mRNA levels has been suggested for predicting the immunomodulatory potential of chemicals. To obtain evidence of the innate immune responses to B[a]P in Xenopus laevis, the present study monitored the mRNA expression of interleukin 1-beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha) and heat shock protein 70 (HSP70) in a laboratorial exposure. Tadpoles exposed to 8.36, 14.64, 89.06 and 309.47 MUg/L of B[a]P,were used for detecting hsp70, IL-1beta and TNF-alpha mRNA induction. A dose-response increase in the expression of hsp70 and IL-1beta mRNA was found. The results of this study confirmed the use of hsp70 and IL-1beta, but not TNF alpha, as sensitive indicators of immunotoxic effect of B[a]P in X. laevis. Further research would be required for the validation of these endpoints. PMID- 22035923 TI - An integrated method for removal of harmful cyanobacterial blooms in eutrophic lakes. AB - As the eutrophication of lakes becomes an increasingly widespread phenomenon, cyanobacterial blooms are occurring in many countries. Although some research has been reported, there is currently no good method for bloom removal. We propose here a new two-step integrated approach to resolve this problem. The first step is the inactivation of the cyanobacteria via the addition of H(2)O(2). We found 60 mg/L was the lowest effective dose for a cyanobacterial concentration corresponding to 100 MUg/L chlorophyll-a. The second step is the flocculation and sedimentation of the inactivated cyanobacteria. We found the addition of lake sediment clay (2 g/L) plus polymeric ferric sulfate (20 mg/L) effectively deposited them on the lake bottom. Since algaecides and flocculants had been used separately in previous reports, we innovatively combined these two types of reagents to remove blooms from the lake surface and to improve the dissolved oxygen content of lake sediments. PMID- 22035924 TI - Adsorption of trace metals to plastic resin pellets in the marine environment. AB - Plastic production pellets collected from beaches of south west England contain variable concentrations of trace metals (Cr, Co, Ni, Cu, Zn, Cd and Pb) that, in some cases, exceed concentrations reported for local estuarine sediments. The rates and mechanisms by which metals associate with virgin and beached polyethylene pellets were studied by adding a cocktail of 5 MUg L(-1) of trace metals to 10 g L(-1) pellet suspensions in filtered seawater. Kinetic profiles were modelled using a pseudo-first-order equation and yielded response times of less than about 100 h and equilibrium partition coefficients of up to about 225 ml g(-1) that were consistently higher for beached pellets than virgin pellets. Adsorption isotherms conformed to both the Langmuir and Freundlich equations and adsorption capacities were greater for beached pellets than for virgin pellets. Results suggest that plastics may represent an important vehicle for the transport of metals in the marine environment. PMID- 22035925 TI - A comparison of POPs bioaccumulation in Eisenia fetida in natural and artificial soils and the effects of aging. AB - The close relationship between soil organic matter and the bioavailability of POPs in soils suggests the possibility of using it for the extrapolation between different soils. The aim of this study was to prove that TOC content is not a single factor affecting the bioavailability of POPs and that TOC based extrapolation might be incorrect, especially when comparing natural and artificial soils. Three natural soils with increasing TOC and three artificial soils with TOC comparable to these natural soils were spiked with phenanthrene, pyrene, lindane, p,p'-DDT, and PCB 153 and studied after 0, 14, 28, and 56 days. At each sampling point, total soil concentration and bioaccumulation in earthworms Eisenia fetida were measured. The results showed different behavior and bioavailability of POPs in natural and artificial soils and apparent effects of aging on these differences. Hence, direct TOC based extrapolation between various soils seems to be limited. PMID- 22035926 TI - Forests under climate change and air pollution: gaps in understanding and future directions for research. AB - Forests in Europe face significant changes in climate, which in interaction with air quality changes, may significantly affect forest productivity, stand composition and carbon sequestration in both vegetation and soils. Identified knowledge gaps and research needs include: (i) interaction between changes in air quality (trace gas concentrations), climate and other site factors on forest ecosystem response, (ii) significance of biotic processes in system response, (iii) tools for mechanistic and diagnostic understanding and upscaling, and (iv) the need for unifying modelling and empirical research for synthesis. This position paper highlights the above focuses, including the global dimension of air pollution as part of climate change and the need for knowledge transfer to enable reliable risk assessment. A new type of research site in forest ecosystems ("supersites") will be conducive to addressing these gaps by enabling integration of experimentation and modelling within the soil-plant-atmosphere interface, as well as further model development. PMID- 22035927 TI - Comparison of arsenate and cadmium toxicity in a freshwater amphipod (Gammarus pulex). AB - Cadmium is largely documented on freshwater organisms while arsenic, especially arsenate, is rarely studied. The kinetic of the LC50s values for both metals was realized on Gammarus pulex. Physiological [i.e. metal concentration in body tissues, bioconcentration factor (BCF)] effects and behavioural responses (via pleopods beats) were investigated after 240-h exposure. Arsenate LC50 value was 100 fold higher than Cd-LC50 value after 240-h exposure, while concentrations in gammarids were similar for both metals at their respective LC50s. BCF decreased with increasing cadmium concentration while BCF remained stable with increasing arsenate concentration. Moreover, BCF was between 148 and 344 times lower for arsenate than cadmium. A significant hypoventilation was observed for cadmium concentrations exceeding or close to the 240h-LC50(Cd), while gammarids hyperventilated for the lowest arsenate concentrations and hypoventilated for the highest arsenate concentrations. We discussed the relationships between potential action mechanisms of these two metals and observed results. PMID- 22035928 TI - Ambient ozone effects on gas exchange and total non-structural carbohydrate levels in cutleaf coneflower (Rudbeckia laciniata L.) growing in Great Smoky Mountains National Park. AB - Ozone-sensitive and -tolerant individuals of cutleaf coneflower (Rudbeckia laciniata L.) were compared for their gas exchange characteristics and total non structural carbohydrates at Purchase Knob, a high elevation site in Great Smoky Mountains National Park, USA. Photosynthesis and stomatal conductance decreased with increased foliar stipple. Sensitive plants had lower photosynthetic rates for all leaves, except the very youngest and oldest when compared to tolerant plants. Stomatal conductance decreased with increasing leaf age, but no ozone sensitivity differences were found. Lower leaves had less starch than upper ones, while leaves on sensitive plants had less than those on tolerant plants. These results show that ambient levels of ozone in Great Smoky Mountains National Park can adversely affect gas exchange, water use efficiency and leaf starch content in sensitive coneflower plants. Persistence of sensitive genotypes in the Park may be due to physiological recovery in low ozone years. PMID- 22035929 TI - Potential sources of methylmercury in tree foliage. AB - Litterfall is a major source of mercury (Hg) and toxic methylmercury (MeHg) to forest soils and influences exposures of wildlife in terrestrial and aquatic ecosystems. However, the origin of MeHg associated with tree foliage is largely unknown. We tested the hypothesis that leaf MeHg is influenced by root uptake and thereby related to MeHg levels in soils. Concentrations of MeHg and total Hg in deciduous and coniferous foliage were unrelated to those in soil at 30 urban and rural forested locations in southwest Ohio. In contrast, tree genera and trunk diameter were significant variables influencing Hg in leaves. The fraction of total Hg as MeHg averaged 0.4% and did not differ among tree genera. Given that uptake of atmospheric Hg(0) appears to be the dominant source of total Hg in foliage, we infer that MeHg is formed by in vivo transformation of Hg in proportion to the amount accumulated. PMID- 22035930 TI - Levels and distribution patterns of short chain chlorinated paraffins in sewage sludge of wastewater treatment plants in China. AB - Short chain chlorinated paraffins (SCCPs) are listed as persistent organic pollutant candidates in the Stockholm Convention and are receiving more and more attentions worldwide. In general, concentrations of contaminants in sewage sludge can give an important indication on their pollution levels at a local/regional basis. In this study, SCCPs were investigated in sewage sludge samples collected from 52 wastewater treatment plants in China. Concentrations of total SCCPs (SigmaSCCPs) in sludge were in the range of 0.80-52.7 MUg/g dry weight (dw), with a mean value of 10.7 MUg/g dw. Most of SCCPs in the sludge samples showed a similar congener distribution patterns, and C(11) and Cl(7,8) were identified as the dominant carbon and chlorine congener groups. Significant linear relationships were found among different SCCP congener groups (r(2) >= 0.9). High concentrations of SCCPs in sewage sludge imply that SCCPs are widely present in China. PMID- 22035931 TI - A mesocosm approach for detecting stream invertebrate community responses to treated wastewater effluent. AB - The discharge of wastewater from sewage treatment plants is one of the most common forms of pollution to river ecosystems, yet the effects on aquatic invertebrate assemblages have not been investigated in a controlled experimental setting. Here, we use a mesocosm approach to evaluate community responses to exposure to different concentrations of treated wastewater effluents over a two week period. Multivariate analysis using Principal Response Curves indicated a clear, dose-effect response to the treatments, with significant changes in macroinvertebrate assemblages after one week when exposed to 30% effluent, and after two weeks in the 15% and 30% effluent treatments. Treatments were associated with an increase in nutrient concentrations (ammonium, sulfate, and phosphate) and reduction of dissolved oxygen. These findings indicate that exposure to wastewater effluent cause significant changes in abundance and composition of macroinvertebrate taxa and that effluent concentration as low as 5% can have detectable ecological effects. PMID- 22035932 TI - Fate of Triclosan and Methyltriclosan in soil from biosolids application. AB - This study investigates the persistence of Triclosan (TCS), and its degradation product, Methyltriclosan (MeTCS), after land application of biosolids to an experimental agricultural plot under both till and no till. Surface soil samples (n = 40) were collected several times over a three years period and sieved to remove biosolids. Concentration of TCS in the soil gradually increased with maximum levels of 63.7 +/- 14.1 ng g(-1) dry wt., far below the predicted maximum concentration of 307.5 ng g(-1) dry wt. TCS disappearance corresponded with MeTCS appearance, suggesting in situ formation. Our results suggest that soil incorporation and degradation processes are taking place simultaneously and that TCS background levels are achieved within two years. TCS half-life (t(0.5)) was determined as 104 d and MeTCS t(0.5), which was more persistent than TCS, was estimated at 443 d. PMID- 22035933 TI - Insights into low fish mercury bioaccumulation in a mercury-contaminated reservoir, Guizhou, China. AB - We examined Hg biogeochemistry in Baihua Reservoir, a system affected by industrial wastewater containing mercury (Hg). As expected, we found high levels of total Hg (THg, 664-7421 ng g(-1)) and monomethylmercury (MMHg, 3-21 ng g(-1)) in the surface sediments (0-10 cm). In the water column, both THg and MMHg showed strong vertical variations with higher concentrations in the anoxic layer (>4m) than in the oxic layer (0-4 m), which was most pronounced for the dissolved MMHg (p < 0.001). However, mercury levels in biota samples (mostly cyprinid fish) were one order of magnitude lower than common regulatory values (i.e. 0.3-0.5 mg kg( 1)) for human consumption. We identified three main reasons to explain the low fish Hg bioaccumulation: disconnection of the aquatic food web from the high MMHg zone, simple food web structures, and biodilution effect at the base of the food chain in this eutrophic reservoir. PMID- 22035934 TI - Blood Pb and delta-ALAD inhibition in cattle and sheep from a Pb-polluted mining area. AB - The effects of Pb pollution on cattle and sheep raised in an ancient mining area were studied through the use of blood Pb (PbB) levels and delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Lead levels in livestock blood from the mining area (n=110) were significantly elevated when compared to the controls (n=79). In 91.4% of cattle (n=58) and 13.5% of sheep (n=52) sampled in the mining area, PbB levels corresponded to subclinical exposure (6-35 MUg/dl). Two young cattle (<2 years) from the mining area (n=5) had PbB levels indicative of clinical poisoning (>35 MUg/dl). Elevated PbB was also accompanied by delta-ALAD activity inhibition in blood, which confirms that measurable effects of Pb poisoning were taking place. Observed PbB levels suggest that a potential risk to human consumers of beef from the Pb polluted areas may also exist, as has been shown previously for game meat from the same mining area. PMID- 22035935 TI - On the use of a freeze-dried versus an air-dried soil humic acid as a surrogate of soil organic matter for contaminant sorption. AB - The sorption of phenanthrene (PHN) to relatively pure soil humic acids (HAs) was investigated to assess the suitability of the soil HA as a surrogate sorbent for the soil organic matter (SOM). The HAs were prepared in both freeze-dried and air dried forms. The two forms of HAs from the same source are similar in composition but the freeze-dried HAs exhibit a significantly higher initial surface area (SA) (3.86-4.59 m(2)/g); the SAs of air-dried HAs are below 0.1 m(2)/g. However, the SAs of freeze-dried HAs are not stable upon contact with water; the samples lose practically all the SA after 4 days of immersion in water. The PHN sorption to both forms of HAs is practically linear, whether a co-solute is present or not. The sorption linearity observed with the present freeze-dried HAs is in sharp contrast with the allegedly nonlinear PHN sorption on similar freeze-dried HAs as presented by others. PMID- 22035936 TI - Bioaccessibility of trace elements as affected by soil parameters in smelter contaminated agricultural soils: a statistical modeling approach. AB - An investigation was undertaken to identify the most significant soil parameters that can be used to predict Cd, Pb, and Zn bioaccessibility in smelter contaminated agricultural soils. A robust model was established from an extended database of soils by using: (i) a training set of 280 samples to select the main soil parameters, to define the best population to be taken into account for the model elaboration, and to construct multivariate regression models, and (ii) a test set of 110 samples to validate the ability of the regression models. Total carbonate, organic matter, sand, P(2)O(5), free Fe-Mn oxide, and pseudototal Al and trace element (TE) contents appeared as the main variables governing TE bioaccessibility. The statistical modeling approach was reasonably successful, indicating that the main soil factors influencing the bioaccessibility of TEs were taken into account and the predictions could be applicable for further risk evaluation in the studied area. PMID- 22035937 TI - Metal stress and decreased tree growth in response to biosolids application in greenhouse seedlings and in situ Douglas-fir stands. AB - To assess physiological impacts of biosolids on trees, metal contaminants and phytochelatins were measured in Douglas-fir stands amended with biosolids in 1982. A subsequent greenhouse study compared these same soils to soils amended with fresh wastewater treatment plant biosolids. Biosolids-amended field soils had significantly higher organic matter, lower pH, and elevated metals even after 25 years. In the field study, no beneficial growth effects were detected in biosolids-amended stands and in the greenhouse study both fresh and historic biosolids amendments resulted in lower seedling growth rates. Phytochelatins - bioindicators of intracellular metal stress - were elevated in foliage of biosolids-amended stands, and significantly higher in roots of seedlings grown with fresh biosolids. These results demonstrate that biosolids amendments have short- and long-term negative effects that may counteract the expected tree growth benefits. PMID- 22035938 TI - Assessing single and joint effects of chemicals on the survival and reproduction of Folsomia candida (Collembola) in soil. AB - Chemicals are often found in the environment as complex mixtures. There has been a large effort in the last decade to assess the combined effect of chemicals, using the conceptual models of Concentration Addition and Independent Action, but also including synergistic, antagonistic, dose-level and dose-ratio dependent deviations from these models. In the present study, single and mixture toxicity of atrazine, dimethoate, lindane, zinc and cadmium were studied in Folsomia candida, assessing survival and reproduction. Different response patterns were observed for the different endpoints and synergistic patterns were observed when pesticides were present. Compared with the previously tested Enchytraeus albidus and Porcellionides pruinosus, the mixture toxicity pattern for F. candida was species specific. The present study highlights the importance of studying toxicity of chemicals mixtures due to the observed potentiation of effects and confirms that for an adequate ecologically relevant risk assessment different organisms and endpoints should be included. PMID- 22035939 TI - Concentrations of methylmercury in invertebrates from wetlands of the Prairie Pothole Region of North America. AB - Prairie wetlands may be important sites of mercury (Hg) methylation resulting in elevated methylmercury (MeHg) concentrations in water, sediments and biota. Invertebrates are an important food resource and may act as an indicator of MeHg exposure to higher organisms. In 2007-2008, invertebrates were collected from wetland ponds in central Saskatchewan, categorized into functional feeding groups (FFGs) and analyzed for total Hg (THg) and MeHg. Methylmercury and THg concentrations in four FFGs ranged from 0.2-393.5 ng . g(-1) and 9.7-507.1 ng . g(-1), respectively. Methylmercury concentrations generally increased from gastropods with significantly lower average MeHg concentrations compared to other invertebrate taxa. Surrounding land use (agricultural, grassland and organic agricultural) may influence MeHg concentrations in invertebrates, with invertebrate MeHg concentrations being higher from organic ponds (457.5 +/- 156.7 ng . g(-1)) compared to those from grassland ponds (74.8 +/- 14.6 ng . g(-1)) and ponds on agricultural lands (32.8 +/- 6.2 ng . g(-1)). PMID- 22035940 TI - Effect of recent climate change on Arctic Pb pollution: a comparative study of historical records in lake and peat sediments. AB - Historical changes of anthropogenic Pb pollution were reconstructed based on Pb concentrations and isotope ratios in lake and peat sediment profiles from Ny Alesund of Arctic. The calculated excess Pb isotope ratios showed that Pb pollution largely came from west Europe and Russia. The peat profile clearly reflected the historical changes of atmospheric deposition of anthropogenic Pb into Ny-Alesund, and the result showed that anthropogenic Pb peaked at 1960s 1970s, and thereafter a significant recovery was observed by a rapid increase of (206)Pb/(207)Pb ratios and a remarkable decrease in anthropogenic Pb contents. In contrast to the peat record, the longer lake record showed relatively high anthropogenic Pb contents and a persistent decrease of (206)Pb/(207)Pb ratios within the uppermost samples, suggesting that climate-sensitive processes such as catchment erosion and meltwater runoff might have influenced the recent change of Pb pollution record in the High Arctic lake sediments. PMID- 22035941 TI - Trend and concentrations of legacy lead (Pb) in highway runoff. AB - This study presents the results of lead (Pb) concentrations from both highway runoff and contaminated soil along 32 and 23 highway sites, respectively. In general, the Pb concentration on topsoil (0-15 cm) along highways was much higher than the Pb concentration in subsurface soil (15-60 cm). The Pb deposited on soil appears to be anthropogenic and a strong correlation was found between the Pb concentration in surface soil and highway runoff in urban areas. The concentration of Pb measured during 1980s from highways runoff throughout the world was up to 11 times higher than the measured values in mid 1990 s and 2000s. The current Pb deposited on soil near highways appears to be a mixture of paint, tire weight balance and old leaded gasoline combustion. Overall, the Pb phase-out regulation reduced the Pb deposits in the environment and consequently lowered Pb loading into receiving waters. PMID- 22035942 TI - Cosorption of organic chemicals with different properties: their shared and different sorption sites. AB - Complementary sorption of different chemicals was expected and investigating the relationship between the sorption inhibition of primary sorbate (DeltaQ(pri)) and sorption of secondary sorbate (Q(sec)) could provide a new angle to understand coadsorption of different chemicals. This study used bisphenol A (BPA) as the primary adsorbate, sulfamethoxazole (SMX) as the competitor, and carbon nanotubes as model adsorbents to study their complementary and competitive adsorption. At low BPA concentrations, the sorption of SMX (Q(sec)) exceeded BPA sorption inhibition (DeltaQ(pri)), indicating that these two chemicals complementarily adsorbed on their respectively preferred sorption sites. At high BPA concentrations, higher DeltaQ(pri) was observed in comparison to Q(sec), which may be resulted from different packing efficiencies of the adsorbed SMX and BPA. This study emphasized that both competitive and complementary sorption should be discussed in binary sorption system. PMID- 22035943 TI - Aqueous uptake and sublethal toxicity of p,p'-DDE in non-feeding larval stages of Antarctic krill (Euphausia superba). AB - This study evaluated the toxicological sensitivity of non-feeding larval stages of a key Antarctic species (Antarctic krill, Euphausia superba) to p,p' dichlorodiphenyl dichloroethylene (p,p'-DDE) exposure. The aqueous uptake clearance rate of 84 mL g(-1) preserved weight (p.w.) h(-1) determined for p,p' DDE in Antarctic krill larvae is comparable to previous findings for small cold water crustaceans and five times slower than the rates reported for an amphipod inhabiting warmer waters. Natural variations in larval physiology appear to influence contaminant uptake and larval krill behavioural responses, strongly highlighting the importance of time of measurement for ecotoxicological testing. Sublethal narcosis (immobility) was observed in larval Antarctic krill from p,p' DDE body residues of 0.2 mmol/kg p.w., which is in agreement with findings for adult krill and temperate aquatic species. The finding of comparable body residue based toxicity of p,p'-DDE between polar and temperate species supports the tissue residue approach for environmental risk assessment of polar ecosystems. PMID- 22035944 TI - Emissions of nitric oxide from 79 plant species in response to simulated nitrogen deposition. AB - To assess the potential contribution of nitric oxide (NO) emission from the plants grown under the increasing nitrogen (N) deposition to atmospheric NO budget, the effects of simulated N deposition on NO emission and various leaf traits (e.g., specific leaf area, leaf N concentration, net photosynthetic rate, etc.) were investigated in 79 plant species classified by 13 plant functional groups. Simulated N deposition induced the significant increase of NO emission from most functional groups, especially from conifer, gymnosperm and C(3) herb. Moreover, the change rate of NO emission was significantly correlated with the change rate of various leaf traits. We conclude that the plants grown under atmospheric N deposition, especially in conifer, gymnosperm and C(3) herb, should be taken into account as an important biological source of NO and potentially contribute to atmospheric NO budget. PMID- 22035945 TI - The impact of verbal instructions on goal-directed behaviour. AB - It is common to use verbal instructions when performing complex tasks. To evaluate how such instructions contribute to cognitive control, mixing costs (as a measure of sustained concentration on task) were evaluated in two task switching experiments combining the list and alternating runs paradigms. Participants responded to bivalent stimuli according to a characteristic explicitly defined by a visually presented instructional cue. The processing of the cue was conducted under four conditions across the two experiments: Silent Reading, Reading Aloud, Articulatory Suppression, and dual mode (visual and audio) presentation. The type of cue processing produced a substantial impact on the mixing costs, where its magnitude was greatest with articulatory suppression and minimal with reading aloud and dual mode presentations. Interestingly, silently reading the cue only provided medium levels of mixing cost. The experiments demonstrate that relevant verbal instructions boost sustained concentration on task goals when maintaining multiple tasks. PMID- 22035947 TI - Late preterm birth: more and better data needed. PMID- 22035946 TI - Evolution of sex and mating loci: an expanded view from Volvocine algae. AB - Sexual reproduction in Volvocine algae coevolved with the acquisition of multicellularity. Unicellular genera such as Chlamydomonas and small colonial genera from this group have classical mating types with equal-sized gametes, while larger multicellular genera such as Volvox have differentiated males and females that produce sperm and eggs respectively. Newly available sequence from the Volvox and Chlamydomonas genomes and mating loci open up the potential to investigate how sex-determining regions co-evolve with major changes in development and sexual reproduction. The expanded size and sequence divergence between the male and female haplotypes of the Volvox mating locus (MT) not only provide insights into how the colonial Volvocine algae might have evolved sexual dimorphism, but also raise questions about why the putative ancestral-like MT locus in Chlamydomonas shows less divergence between haplotypes than expected. PMID- 22035948 TI - Editors' note on notice of retraction. PMID- 22035950 TI - Nonspontaneous late preterm birth: etiology and outcomes. AB - OBJECTIVE: We sought to determine the proportion of evidence-based (EB), vs non EB (NEB) iatrogenic late preterm birth, and to compare corresponding rates of neonatal intensive care unit (NICU) admission. STUDY DESIGN: We performed a retrospective cohort study. Cases were categorized as EB or NEB. NICU admission was compared between groups in both univariate and multivariate analysis. RESULTS: Of 2693 late preterm deliveries, 32.3% (872/2693) were iatrogenic; 56.7% were delivered for NEB indications. Women with NEB deliveries were older (30.0 vs 28.6 years, P = .001), and more likely to be pregnant with twins (18.8% vs 7.9%, P < .001), have private insurance (80.3% vs 59.0%, P < .001), or have a second complicating factor (27.5% vs 10.1%, P < .001). A total of 56% of EB deliveries resulted in NICU admissions. After controlling for confounders, early gestational age (34 vs 36 weeks: odds ratio, 19.34; 95% confidence interval, 4.28-87.5) and mode of delivery (cesarean: odds ratio, 1.88; 95% confidence interval, 1.15-3.05) were most strongly associated with NICU admission. CONCLUSION: Over half of nonspontaneous late preterm births were NEB. EB guidelines are needed. PMID- 22035951 TI - Leiomyoma-related hospitalization and surgery: prevalence and predicted growth based on population trends. AB - OBJECTIVE: To estimate leiomyoma-related inpatient care in the United States for 2007 with predictions for the ensuing 40 years. STUDY DESIGN: We used the 2007 Nationwide Inpatient Sample to estimate hospitalizations and inpatient surgeries for uterine leiomyoma in US women 15 to 54 years. We used the US Census Bureau population projections to predict leiomyoma-related inpatient care through 2050. RESULTS: In 2007, 355,135 women were hospitalized for leiomyoma (rate = 42 per 10,000 women-years). Black women had increased rates of hospitalization, hysterectomy, and myomectomy (relative risk, 3.5, 2.4, 6.8, respectively) compared with white women. Leiomyoma-related hospitalizations are predicted to increase 23% (to 437,874) between 2007 and 2050, with 20% and 31% increases in leiomyoma-related hysterectomies and myomectomies. CONCLUSION: Leiomyoma-related inpatient care and major surgery remains substantial despite advances in less invasive treatment options. Given population growth, the projected burden of leiomyoma-related inpatient care will increase significantly by 2050, differentially impacting black vs white women. PMID- 22035952 TI - A peculiar site: melanoma of the cervix. PMID- 22035953 TI - Discussion: 'placental dysfunction disorders across generations' by Wikstrom et al. AB - In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Wikstrom A-K, Svensson T, Kieler H, et al. Recurrence of placental dysfunction disorders across generations. Am J Obstet Gynecol 2011;205:454.e1-8. PMID- 22035954 TI - Spontaneous prelabor uterine rupture in a primigravida: a case report and review of the literature. AB - A rare case of prelabor uterine rupture in a primigravida was reported. A woman with a history of uterine perforation during hysteroscopy became pregnant after donor oocyte in vitro fertilization. To provide more insight into the possible risk factors for prelabor uterine rupture in primigravidae, a literature review was performed. PMID- 22035955 TI - Effect of omega-3 polyunsaturated fatty acids to reverse biopsy-proven parenteral nutrition-associated liver disease in adults. AB - BACKGROUND & AIMS: Parenteral nutrition-associated liver disease (PNALD) complicates the treatment of patients with short bowel syndrome (SBS). Some studies have shown omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have favorable effects in treating PNALD in children. We, therefore, investigate the effects of omega-3 PUFAs supplemented intravenous lipid emulsion (ILE) on PNALD in adults. METHODS: We performed an open-labeled study of a omega-3 PUFAs based ILE in 15 adults with SBS who developed cholestasis while receiving soybean oil based ILE. Liver biopsies were performed before and after the initiation of omega 3 PUFAs to confirm the presence and improvement of cholestasis. Blood samples were collected every week for analysis of fatty acid composition and liver function. RESULTS: 12 of the 15 patients had their direct bilirubin normalized within 4 weeks and our data demonstrated a significant decrease in both DB (P <= 0.001) and TB (P <= 0.001) after 4 weeks compared to baseline. There were ameliorations of liver function and fatty acid patterns in all patients and serial liver biopsy specimens showed progressive histologic improvement. CONCLUSIONS: Parenteral omega-3 PUFAs supplemented fat emulsions are safe and effective in the treatment of PNALD in adults. PMID- 22035956 TI - Integrated nutritional intervention in the elderly after hip fracture. A process evaluation. AB - BACKGROUND & AIMS: Within a multicentre randomized controlled trial aimed at improving the nutritional status and increase the speed of recovery of elderly hip fracture patients, we performed a process evaluation to investigate the feasibility of the intervention within the present Dutch health care system. METHODS: Patients in the intervention group received nutritional counseling during 10 contacts. Oral nutritional supplements were advised as needed until three months after hip fracture surgery. The intervention was evaluated with respect to dieticians' adherence to the study protocol, content of nutritional counseling, and patients' adherence to recommendations given. RESULTS: We included 66 patients (mean age of 76, range 55-92 years); 74% women. Eighty-three percent of patients received all 10 contacts as planned, but in 62% of the patients one or more telephone calls had to be replaced by face to face contacts. Nutritional counseling was complete in 91% of contacts. Oral nutritional supplementation was needed for a median period of 76 days; 75% of the patients took the oral nutritional supplements as recommended. CONCLUSIONS: Nutritional counseling in elderly hip fracture patients through face to face contacts and telephone calls is feasible. However, individual tailoring of the intervention is recommended. The majority of hip fracture patients needed >2 months oral nutritional supplements to meet their nutritional requirements. The trial was registered at clincialtrails.gov as NCT00523575. PMID- 22035957 TI - Clinical review of 28 patients with basilar artery occlusion. AB - BACKGROUND: We retrospectively analyzed factors related to the outcomes of patients with basilar artery occlusion. METHODS: Twenty-eight patients with basilar artery occlusion admitted to our hospital within 24 hours after onset between April 2007 and December 2010 were included. We investigated parameters related to outcome, such as coexisting disease, clinical type, clinical severity at admission, the site of occlusion and the infarction lesion, the collateral flow from posterior communicating artery, therapy, and time to therapy after onset. RESULTS: Of 28 patients with basilar artery occlusion, good outcomes occurred in 6 patients (21%) and poor outcomes occurred in 22 patients (79%). Clinical severity on admission was significantly different between the 2 groups. Three of 5 patients with percutaneous transluminal angioplasty achieved recanalization. Two of 3 cases with recanalization resulted in poor outcomes. CONCLUSIONS: Clinical severity on admission was the determinant factor of functional prognosis in patients with basilar artery occlusion. PMID- 22035958 TI - A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans. AB - Sterol regulatory element-binding proteins (SREBPs) activate genes involved in the synthesis and trafficking of cholesterol and other lipids and are critical for maintaining lipid homeostasis. Aberrant SREBP activity, however, can contribute to obesity, fatty liver disease, and insulin resistance, hallmarks of metabolic syndrome. Our studies identify a conserved regulatory circuit in which SREBP-1 controls genes in the one-carbon cycle, which produces the methyl donor S adenosylmethionine (SAMe). Methylation is critical for the synthesis of phosphatidylcholine (PC), a major membrane component, and we find that blocking SAMe or PC synthesis in C. elegans, mouse liver, and human cells causes elevated SREBP-1-dependent transcription and lipid droplet accumulation. Distinct from negative regulation of SREBP-2 by cholesterol, our data suggest a feedback mechanism whereby maturation of nuclear, transcriptionally active SREBP-1 is controlled by levels of PC. Thus, nutritional or genetic conditions limiting SAMe or PC production may activate SREBP-1, contributing to human metabolic disorders. PMID- 22035959 TI - The processing of extraposed structures in English. AB - In most languages, most of the syntactic dependency relations found in any given sentence are projective: the word-word dependencies in the sentence do not cross each other. Some syntactic dependency relations, however, are non-projective: some of their word-word dependencies cross each other. Non-projective dependencies are both rarer and more computationally complex than projective dependencies; hence, it is of natural interest to investigate whether there are any processing costs specific to non-projective dependencies, and whether factors known to influence processing of projective dependencies also affect non projective dependency processing. We report three self-paced reading studies, together with corpus and sentence completion studies, investigating the comprehension difficulty associated with the non-projective dependencies created by the extraposition of relative clauses in English. We find that extraposition over either verbs or prepositional phrases creates comprehension difficulty, and that this difficulty is consistent with probabilistic syntactic expectations estimated from corpora. Furthermore, we find that manipulating the expectation that a given noun will have a postmodifying relative clause can modulate and even neutralize the difficulty associated with extraposition. Our experiments rule out accounts based purely on derivational complexity and/or dependency locality in terms of linear positioning. Our results demonstrate that comprehenders maintain probabilistic syntactic expectations that persist beyond projective-dependency structures, and suggest that it may be possible to explain observed patterns of comprehension difficulty associated with extraposition entirely through probabilistic expectations. PMID- 22035960 TI - Th17 expansion in MS patients is counterbalanced by an expanded CD39+ regulatory T cell population during remission but not during relapse. AB - In this study, percentages of CD39(+) Treg and Th17 cells were compared between relapsing-remitting MS patients and controls and were related to the vitamin D status. The Th17 cell population was expanded in about 40% of the MS patients. In MS patients in remission, but not during relapse, a positive association was found between Th17 cell and CD39(+) Treg percentages (r=0.468, p=0.007). Since CD39(+) Tregs have been shown to have Th17 suppressive capacities, we propose that a dysregulated Th17/CD39(+) Treg balance might contribute to disease exacerbation. A clear role for vitamin D in this regulation could not be established. PMID- 22035961 TI - Cladribine inhibits cytokine secretion by T cells independently of deoxycytidine kinase activity. AB - Cladribine (2-chloro-2'-deoxyadenosine) is a purine nucleoside analogue (PNA) which causes targeted and sustained reduction of peripheral lymphocyte counts. Cladribine tablets produced significant treatment benefit for patients with relapsing-remitting multiple sclerosis in the phase 3 CLARITY study. In addition to the well-characterised cell-specific phosphorylation of PNAs responsible for lymphocyte reduction, the mode of action of cladribine may encompass distinct activities contributing to its overall effects on the immune system. Here we demonstrate that clinically relevant concentrations of cladribine also inhibit cytokine secretion by human peripheral blood T cells in vitro through mechanisms independent of the induction of lymphocyte death. PMID- 22035962 TI - Replacement of continuous-flow left ventricular assist device via left subcostal incision. PMID- 22035963 TI - Ideal site for ventricular anchoring of artificial chordae in mitral regurgitation. AB - OBJECTIVE: Surgical treatment of mitral leaflet prolapse using artificial neochordae shows excellent outcomes. Upcoming devices attempt the same treatment in a minimally invasive way but target the left ventricular apex as an anchoring point, rather than the tip of the corresponding papillary muscle. In this study, cine cardiac magnetic resonance imaging was used to compare these 2 different anchoring positions and their dynamic relationship with the mitral leaflets. METHODS: Eleven healthy volunteers (mean age, 31 years; 6 female; mean ejection fraction, 62%) were examined by cardiac magnetic resonance imaging (3 Tesla, cine steady free precession technique with retrospective gating), whereby dedicated software enabled assessment of the physiologic distances among 3 anchoring sites (anterior papillary muscle, posterior papillary muscle, and apex) and the plane of the mitral annulus at the level of leaflet coaptation. These distances were measured in systole and diastole, and the performance of virtual neochordae was analyzed for the 3 potential anchoring sites. RESULTS: Length difference between systole and diastole for the 3 measured distances were 0.19 +/- 0.11 cm (5.9% +/- 3.4%) for the anterior papillary muscle, 0.19 +/- 0.09 cm (6.7% +/- 3.6%) for the posterior papillary muscle, and 1.52 +/- 0.18 cm (17.8% +/- 2.8%) for the left ventricular apex (P = .001). Virtual neochordae between the leaflet and the left ventricular apex were first adjusted in systole to achieve leaflet coaptation. Leaflet tear in diastole can only be avoided if the width of the attached leaflet is larger than the systole-diastole length difference. On the other hand, if virtual neochordae are adjusted in diastole to avoid leaflet tear, residual leaflet prolapse during systole can result. Because the systole-diastole length difference for papillary muscle anchored chordae is smaller than for apical chordae by a factor 10, there is a strongly reduced risk of prolapse or tearing and the leaflet width is unimportant. Furthermore, if the neochordae attached to the anterior mitral leaflet uses the apex as a distal anchoring site, the angle alpha between the aortic valve plane and this mitral leaflet is significantly reduced in diastole and therefore increases the risk of systolic anterior motion. CONCLUSIONS: Anchoring of neochordae at the papillary muscles, thereby mimicking the real anatomy, should be preferred over the left ventricular apex. Further analysis of dilated hearts and papillary muscle displacement is necessary to include the whole spectrum of pathologies. PMID- 22035964 TI - Transplantation of alveolar type II cells stimulates lung regeneration during compensatory lung growth in adult rats. AB - OBJECTIVE: It is controversial whether lung regeneration contributes to compensatory lung growth after pulmonary resection in mature individuals. The objectives of this study were to clarify the molecular mechanisms that regulate the process of compensatory lung growth and investigate the influence of transplantation of lung cells enriched in alveolar type II cells on compensatory lung growth. METHODS: Serial changes of morphology and gene expression were examined in the remnant right lung after pneumonectomy in adult male Wistar rats. One day after surgery, animals received endotracheal transplants of rat lung cells enriched in alveolar type II cells at a dose of 2.5 * 10(6) cells. Serial morphologic changes were examined in comparison with pneumonectomy alone. Engraftment of lung cells was validated with a sex-mismatch model. RESULTS: The alveolar density with mean linear intercept was always lower in pneumonectomized rats than in sham surgical controls for 6 months after surgery. Microarray analysis revealed that multiple genes related to proliferation (but not specific alveolar development) were initially up-regulated and then returned to normal after 1 month. In the pneumonectomized rats with transplantation, the alveolar density was equivalent to that in the sham controls. Engraftment of the transplanted cells from male donors in the alveoli of female recipients was proven by detection of Y-chromosome positive cells and quantified by real-time polymerase chain reaction for the Sry gene. This occurred in pneumonectomized rats but not in sham controls. CONCLUSIONS: We postulate that lung cell transplantation stimulates lung regeneration in the remnant lung after pneumonectomy in mature rats. PMID- 22035965 TI - Prophylactic amiodarone reduces junctional ectopic tachycardia after tetralogy of Fallot repair. AB - OBJECTIVE: Junctional ectopic tachycardia is common after pediatric heart surgery. After tetralogy of Fallot repair, the incidence of junctional ectopic tachycardia may be as high as 15% to 20%. We introduced prophylactic amiodarone for tetralogy repair. This study was conducted to evaluate the effectiveness of the prophylactic amiodarone. METHODS: A continuous infusion of amiodarone was started in the operating room at the time of rewarming during cardiopulmonary bypass at a rate of 2 mg/kg/d and continued for 48 hours. Between November 2005 and November 2009, 63 consecutive patients underwent primary repair of tetralogy, of whom 20 had prophylactic amiodarone (amiodarone group) and 43 did not (control group). Variables studied included demographic and bypass data, surgical procedure details (transannular or nontransannular patch), preoperative and postoperative echocardiography findings, and postoperative inotropic support. Univariate and stepwise multivariate analyses were conducted to determine factors associated with the occurrence of junctional ectopic tachycardia. RESULTS: The incidence of junctional ectopic tachycardia was 37% in the control group and 10% in the amiodarone group. The groups were similar in age, weight, bypass time, rate of transannular patch usage, and preoperative and postoperative gradient through the right ventricular outflow tract. Prophylactic amiodarone was significantly negatively associated with junctional ectopic tachycardia by both univariate (P = .039) and multivariate (P = .027) analyses. There were no adverse events attributable to prophylactic amiodarone use. CONCLUSIONS: Prophylactic amiodarone is well tolerated and significantly associated with a decreased incidence of junctional ectopic tachycardia after tetralogy repair. PMID- 22035966 TI - Content validity and internal consistency of the Dutch translation of the Safety Attitudes Questionnaire: an observational study. AB - BACKGROUND: Patient safety is fundamental to healthcare quality. Attention has recently focused on the patient safety culture of an organisation and its impact on patient outcomes. A strong safety climate appears to be an essential condition for safe patient care in the hospital. A number of instruments are used to measure this patient safety climate or culture. The Safety Attitudes Questionnaire is a validated, widely used instrument to investigate multiple dimensions of safety climate at the clinical level in a variety of inpatient and outpatient settings. OBJECTIVES: The purpose of this study is to explore the face and content validity and the internal consistency of the Safety Attitudes Questionnaire in a large Belgian academic medical center. METHOD: The translation into Dutch was done by three researchers. A panel of fifteen Dutch speaking experts evaluated the translation and its content validity. Content validity was quantified by the content validity index (CVI) and a modified kappa index. Face validity was evaluated by two nurses and two physicians who assessed the Dutch version of the SAQ. A cross-sectional design was used to test internal consistency of the SAQ items by calculating Cronbach's alpha and corrected item total correlations. RESULTS: Twenty-three of the 33 SAQ items showed excellent and seven items showed good content validity. One item had a fair kappa value (item 20) and two items had a low content validity index (items 15 and 16). The average CVI of the total scale was 0.83 and ranged from 0.55 to 0.97 for the six subscales. The face-validity was good with no fundamental remarks given. The SAQ's overall Cronbach's alpha was 0.9 and changed minimally when removing items. The item-total correlations ranged from 0.10 to 0.63, no single items were strongly correlated with the sum of the other items. CONCLUSION: We conclude that in this study the Dutch version of the Safety Attitudes Questionnaire showed acceptable to good psychometric properties. In line with previous evidence, this instrument seems to be an acceptable to adequate tool to evaluate the safety climate. PMID- 22035967 TI - Repeated assessment by high-throughput assay demonstrates that sperm DNA methylation levels are highly reproducible. AB - OBJECTIVE: To assess reliability of a high-throughput assay of sperm DNA methylation. DESIGN: Observational study comparing DNA methylation of sperm isolated from 3 divided and 12 longitudinally collected semen samples. SETTING: Academic medical center. PATIENT(S): One man undergoing screening semen analysis during evaluation of an infertile couple and 2 healthy fertile male volunteers. INTERVENTION(S): Spermatozoa were separated from seminal plasma and somatic cells using gradient separation. DNA was extracted from spermatozoa, and DNA methylation was assessed at 1,505 DNA sequence-specific sites. MAIN OUTCOME MEASURE(S): Repeatability of sperm DNA methylation measures, estimated by correlation coefficients. RESULT(S): DNA methylation levels were highly correlated within matched sets of divided samples (all r >= 0.97) and longitudinal samples (average r = 0.97). CONCLUSION(S): The described methodology reliably assessed methylation of sperm DNA at large numbers of sites. Methylation profiles were consistent over time. High-throughput assessment of sperm DNA methylation is a promising tool for studying the role of epigenetic state in male fertility. PMID- 22035968 TI - Viral screening of spent culture media and liquid nitrogen samples of oocytes and embryos from hepatitis B, hepatitis C, and human immunodeficiency virus chronically infected women undergoing in vitro fertilization cycles. AB - OBJECTIVE: To assess the presence of viral RNA or DNA sequences in spent culture media used after ovum pickup (OPU) or embryo culture and in liquid nitrogen (LN) used for oocyte or embryo vitrification in patients seropositive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) undergoing IVF cycles. DESIGN: Descriptive study. SETTING: Private university-affiliated IVF center. PATIENT(S): Twenty-four women who underwent controlled ovarian stimulation for oocyte vitrification or IVF/ET. A total of 6, 11, and 6 patients were seropositive for HIV, HCV, and HBV, respectively, whereas 1 patient showed a coinfection with HCV and HBV. Seven patients presented positive blood viral load (HIV, n = 1; HBV, n = 1; HCV, n = 5). Sixty-three samples were analyzed: follicular fluid, n = 3; spent culture media, n = 33 (20 after OPU and 13 after embryo culture); and LN, n = 27 (14 and 10 after oocyte and embryo vitrification; and 3 LN storage tank samples). INTERVENTION(S): Ovum pickup, oocyte and/or embryo culture, and/or vitrification by the Cryotop open device. Reverse transcription-polymerase chain reaction analysis was performed for viral screening. MAIN OUTCOME MEASURE(S): Detection of viral sequences of HIV, HCV, and HVB. RESULT(S): All the samples analyzed tested negative for the detection of viral RNA or DNA sequences. CONCLUSION(S): We have not detected viral sequences after culture and vitrification of oocytes/embryos from HIV-, HBV , and HCV-seropositive patients. These findings represent good evidence of the lack of risk of cross-contamination among seropositive patients, even using an open device for vitrification. PMID- 22035969 TI - Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies? AB - OBJECTIVE: To review recent data regarding subtle, but widespread, epigenetic alterations in phenotypically normal offspring conceived by assisted reproductive technologies (ART) compared with offspring conceived in vivo. DESIGN: A PubMed computer search was performed to identify relevant articles. SETTING: Research institution. PATIENT(S): Not applicable. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Not applicable. RESULT(S): Studies in animals indicate that in vitro culture may be associated with widespread alterations in imprinted genes compared with in vivo-conceived offspring. Recently, studies in humans have likewise demonstrated widespread changes in DNA methylation, including genes linked to adipocyte development, insulin signaling, and obesity in offspring conceived by ART compared with in vivo-conceived children. Changes in multiple imprinted genes after ART also were noted in additional studies, which suggested that the diagnosis of infertility may explain the differences between in vivo-conceived and ART offspring. CONCLUSION(S): These data suggest that ART is associated with widespread epigenetic modifications in phenotypically normal children, and that these modifications may increase the risk of adverse cardiometabolic outcomes. Further research is needed to elucidate the possible relationship between ART, genome-wide alterations in imprinted genes, and their potential relevance to subtle cardiometabolic consequences reported in ART offspring. PMID- 22035970 TI - Structure and characterization of the 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Aeropyrum pernix. AB - The first enzyme in the shikimic acid biosynthetic pathway, 3-deoxy-D-arabino heptulosonate 7-phosphate synthase (DAH7PS), varies significantly in size and complexity in the bacteria and plants that express it. The DAH7PS from the archaebacterium Aeropyrum pernix (DAH7PS(Ap)) is among the smallest and least complex of the DAH7PS enzymes, leading to the hypothesis that DAH7PS(Ap) would not be subject to feedback regulation by shikimic acid pathway products. We overexpressed DAH7PS(Ap) in Escherichia coli, purified it, and characterized its enzymatic activity. We then solved its X-ray crystal structure with a divalent manganese ion and phosphoenolpyruvate bound (PDB ID: 1VS1). DAH7PS(Ap) is a homodimeric metalloenzyme in solution. Its enzymatic activity increases dramatically above 60 degrees C, with optimum activity at 95 degrees C. Its pH optimum at 60 degrees C is 5.7. DAH7PS(Ap) follows Michaelis-Menten kinetics at 60 degrees C, with a K(M) for erythrose 4-phosphate of 280 MUM, a K(M) for phosphoenolpyruvate of 891 MUM, and a k(cat) of 1.0 s(-1). None of the downstream products of the shikimate biosynthetic pathway we tested inhibited the activity of DAH7PS(Ap). The structure of DAH7PS(Ap) is similar to the structures of DAH7PS from Thermatoga maritima (PDB ID: 3PG8) and Pyrococcus furiosus (PDB ID: 1ZCO), and is consistent with its designation as an unregulated DAH7PS. PMID- 22035971 TI - Managing progressive disease in patients with GIST: factors to consider besides acquired secondary tyrosine kinase inhibitor resistance. AB - The use of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumors (GIST). Currently, imatinib mesylate is the standard first-line treatment for unresectable and/or metastatic GIST, extending recurrence-free and overall survival for many patients. Nonetheless, eventual progression during imatinib therapy is prevalent, and the development of treatment paradigms for managing GIST progression is of importance. Sunitinib malate has been approved as a second line treatment for unresectable and/or metastatic GIST and is an option for patients who are intolerant to imatinib or experience disease progression due to acquired resistance, otherwise referred to as secondary resistance. In many cases, however, there may be other causes for GIST progression besides secondary resistance, and consideration of these factors is necessary before switching to second-line treatment. This review presents a treatment strategy for GIST patients who have progressed after initial imatinib responsiveness and addresses necessary considerations that include instances of false progression, insufficient TKI plasma levels, and patient non-adherence. In situations where true progression has occurred, patients may benefit from imatinib dose escalation. Surgery also provides a viable option for patients with stable disease or limited progression, and may prevent and/or delay the development of resistant clones by reducing tumor burden. Switching to second-line therapy with sunitinib should be considered for imatinib-intolerant or -resistant GIST patients. PMID- 22035972 TI - Enzymatic glucose biosensor based on CeO2 nanorods synthesized by non-isothermal precipitation. AB - Cerium oxide nanorods (CeO(2) NRs) were synthesized without templates through a low cost and simple non-isothermal precipitation method. The structure and morphology of CeO(2) NRs were characterized by X-ray diffraction and transmission electron microscopy. The CeO(2) NRs films, deposited on indium tin oxide (ITO) coated glass substrates through electrophoretic deposition, were used for the immobilization of glucose oxidase (GOx). Field emission scanning electron microscopy, Fourier transform infrared spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy were used to characterize the CeO(2) NRs/ITO and GOx/CeO(2) NRs/ITO electrodes. The GOx/CeO(2) NRs/ITO electrode exhibits a linear range for the detection of glucose from 2 to 26 mM (correlation coefficient: 0.99) at 1-2s response time. Biosensor sensitivity is 0.165 MUA mM( 1) cm(-2) with 100 MUM detection limit. The anti-interference ability of the biosensor was also examined. The mediator-less application of CeO(2) NRs for glucose sensing was demonstrated. PMID- 22035973 TI - An electrochemical sulfite biosensor based on gold coated magnetic nanoparticles modified gold electrode. AB - A sulfite oxidase (SO(X)) (EC 1.8.3.1) purified from Syzygium cumini leaves was immobilized onto carboxylated gold coated magnetic nanoparticles (Fe(3)O(4)@GNPs) electrodeposited onto the surface of a gold (Au) electrode through N-ethyl-N'-(3 dimethylaminopropyl) carbodiimide (EDC)-N-hydroxy succinimide (NHS) chemistry. An amperometric sulfite biosensor was fabricated using SO(X)/Fe(3)O(4)@GNPs/Au electrode as working electrode, Ag/AgCl as standard and Pt wire as auxiliary electrode. The working electrode was characterized by Fourier Transform Infrared (FTIR) Spectroscopy, Cyclic Voltammetry (CV), Scanning Electron Microscopy (SEM) and Electrochemical Impedance Spectroscopy (EIS) before and after immobilization of SO(X). The biosensor showed optimum response within 2s when operated at 0.2V (vs. Ag/AgCl) in 0.1 M Tris-HCl buffer, pH 8.5 and at 35 degrees C. Linear range and detection limit were 0.50-1000 MUM and 0.15 MUM (S/N=3) respectively. Biosensor was evaluated with 96.46% recovery of added sulfite in red wine and 1.7% and 3.3% within and between batch coefficients of variation respectively. Biosensor measured sulfite level in red and white wines. There was good correlation (r=0.99) between red wines sulfite value by standard DTNB (5,5' dithio-bis-(2-nitrobenzoic acid)) method and the present method. Enzyme electrode was used 300 times over a period of 4 months, when stored at 4 degrees C. Biosensor has advantages over earlier biosensors that it has excellent electrocatalysis towards sulfite, lower detection limit, higher storage stability and no interference by ascorbate, cysteine, fructose and ethanol. PMID- 22035974 TI - Binding kinetics of grouper nervous necrosis viruses with functionalized antimicrobial peptides by nanomechanical detection. AB - We report the binding kinetics of fish-infected grouper nervous necrosis viruses (NNV) and selected antimicrobial peptides (AMPs) by nanomechanical detection. AMPs, the vital member in an innate immunity, are promising candidates in the fight against pathogens due to their broad range of antimicrobial activity and low toxicity. Grouper NNV primarily cause mass mortality of many marine cultured fish species, and two selected AMPs in this study were found to inhibit viruses by agglutinating its virions to form aggregates. The binding activity of NNVs with functionalized AMPs onto a sensing microcantilever yielded induced surface stresses, indicating high binding strength of molecular interaction. The binding affinity and kinetic rate constants of molecular recognition events calculated for NNV-AMP(TH1-5) compared to NNV-AMP(cSALF) were found to be 2.1-fold and 4.43 fold, respectively, indicating TH1-5 effectively bind with NNV more than cSALF. Moreover, a microscopic X-ray photoelectron spectroscopy technique was employed for further validation of pre- and post-NNV binding onto peptides-functionalized sensing surface. An increase in the spectrum and intensity of the P 2p and N 1s elements for the post-NNV binding was clearly shown to ensure the existence of phosphate groups and nitrogen-containing ring structures of specific NNV-TH1-5 interaction. Therefore, the microcantilever biosensing technique provides a potential and useful screening of AMPs for affinity to NNVs. PMID- 22035975 TI - Intra-operative fitting study of the PediPump ventricular assist device. PMID- 22035976 TI - Prospective randomized evaluation of a collagen/thrombin and autologous platelet hemostatic agent during total knee arthroplasty. AB - The purpose of this study was to evaluate the effectiveness of a collagen/thrombin and autologous platelet hemostatic agent in preventing blood loss during primary total knee arthroplasty. This prospective, double-blinded, randomized study was designed to enroll a total of 100 patients. Patients were randomized 1:1 to either the treatment arm (standard hemostasis plus study product) or the control arm (standard hemostasis alone). Transfusion requirements, as determined by a blinded investigator using standardized criteria, were significantly lower in the treatment group (no blood transfusions) compared with the control group (5 transfusions; P = .007). These data support the addition of the study product to prevent blood transfusions after primary total knee arthroplasty. PMID- 22035977 TI - Prevention of venous thromboembolism after hip or knee arthroplasty: findings from a 2008 survey of US orthopedic surgeons. AB - A survey was mailed to a representative sample of US orthopedic surgeons to assess protocols for the prevention of venous thromboembolism after lower extremity total joint arthroplasty. Practices were examined by type of operation, annual surgical volume, and opinions of consensus guidelines issued by the American Academy of Orthopaedic Surgeons and the American College of Chest Physicians. Although there was near-unanimous agreement that routine thromboprophylaxis should be the standard practice for patients who undergo hip or knee arthroplasty, surgeons were divided as to the exact management approach. PMID- 22035978 TI - A sensitive and specific HPLC-MS/MS analysis and preliminary pharmacokinetic characterization of isoforskolin in beagle dogs. AB - A sensitive and specific high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method has been developed and validated for the determination of isoforskolin in canine plasma. Liquid liquid extraction was used to extract isoforskolin and the internal standard (I.S.) eplerenone from canine plasma. The chromatographic separation was performed on an Agela Venusil XBP Phenyl column with an isocratic mobile phase consisting of methanol-2mM ammonium acetate-formic acid (62:38:0.1, v/v/v), pumped at 0.35 mL/min. Isoforskolin and I.S. were detected at m/z 433.4->373.3 and m/z 415.3->163.5 in positive ion and multiple reaction monitoring (MRM) mode, respectively. The standard curves were linear over the concentration range of 0.1 200 ng/mL (r>0.99). The intra- and inter-batch accuracy values for isoforskolin at four concentrations were 90.2-108.3% and 97.8-106.6%, respectively. The RSDs were less than 6.0%. The mean extraction recoveries of isoforskolin and I.S. were 97.0 and 88.4%, respectively. The method was successfully applied to the pharmacokinetic study after an intravenous administration of isoforskolin in beagle dogs. PMID- 22035979 TI - Measurement of free and total sialic acid by isotopic dilution liquid chromatography tandem mass spectrometry method. AB - The measurement of urine sialic acid (N Acetylneuraminic Acid: Neu5Ac) is useful for screening sialic acid storage disorders. We developed a new LC MS/MS method for the determination of a sialic acid. Urine samples were analyzed, after an HCl n-Butanol derivatization step, by a reverse phase based high-performance liquid chromatography method using 1,2,3-(13)C(3) N-Acetyl-D-neuraminic Acid ((13)C Neu5Ac) as an internal standard. Selective detection was performed by tandem mass spectrometry using an electrospray source operating in positive ionization mode employing multiple reactions monitoring to monitor N-Acetylneuraminic Acid and the internal standard. The transitions m/z 366->330 and 369->333 for Neu5Ac and (13)C-Neu5Ac were respectively monitored. The limit of the method quantification was 1.40 MUM of N-Acetylneuraminic Acid and the calibration curve showed a good linearity up to 1000 MUM. The within assay precision and accuracy of the method ranged from 3.22 to 5.95% and 98.69 to 109.18%, respectively and the between assay precision and accuracy ranged, respectively, from 5.15 to 7.65% and 96.14 to 102.30%. The method can be applied for the determination of N-Acetylneuraminic Acid concentrations in urine and other biological fluids (e.g., amniotic and peritoneal fluids). PMID- 22035980 TI - Pharmacokinetics and tissue distribution of docetaxel by liquid chromatography mass spectrometry: evaluation of folate receptor-targeting amphiphilic copolymer modified nanostructured lipid carrier. AB - A novel amphiphilic copolymer, folate-poly(PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL) was synthesized to modify docetaxel-loaded nanostructured lipid carrier to lead to a long blood circulating effect and targeting ability for the delivery of antitumor drug in cancer. To investigate the characteristics of modified docetaxel-loaded nanostructured lipid carrier in vivo, a liquid chromatography-mass spectrometry method was developed and validated for the determination of docetaxel in rat plasma and tumor-bearing mouse tissue samples. The biosamples were extracted by liquid-liquid extraction method with ether and separated on a C(18) column (150 mm*4.6 mm, 5 MUm) using a mobile phase consisting of methanol-0.01% formic acid water (82:18, v/v). The standard curves were linear over the ranges of 0.01-4.0 MUg/mL for plasma and 0.02-8.0 MUg/g for tissue samples, respectively. The validated method was successfully applied to the pharmacokinetic study in rat plasma and tissue distribution study in mouse tissues of docetaxel after an intravenous administration of docetaxel injection (DTX injection), docetaxel-loaded nanostructured lipid carrier (DTX-NLC) and FA-PEG-PCHL-modified docetaxel-loaded nanostructured lipid carrier (FA-DTX-NLC), respectively. The results indicated that the FA-DTX-NLC led to significant differences in pharmacokinetic profile and tissue distribution. Nanostructured lipid carrier modified by FA-PEG-PCHL could be one of the promising suspensions for the delivery of docetaxel in cancer. PMID- 22035981 TI - Improvement and validation the method using dispersive liquid-liquid microextraction with in situ derivatization followed by gas chromatography-mass spectrometry for determination of tricyclic antidepressants in human urine samples. AB - A simple, rapid and sensitive method termed dispersive liquid-liquid microextraction (DLLME) combined with gas chromatography-mass spectrometry (GC/MS) was developed for the determination of tricyclic antidepressants (TCAs) in human urine sample. An appropriate mixture of methanol (disperser solvent), carbon tetrachloride (extraction solvent), and acetic anhydride (derivatization reagent) was injected rapidly into human urine sample. After extraction, the sedimented phase was analyzed by GC/MS. The calibration curves obtained with human urine were linear with a correlation coefficient of over 0.99 in the range of 2.0/5.0-100 ng mL(-1). Under the optimum conditions (carbon tetrachloride: 10 MUL, methanol: 150 MUL), the detection limits and the quantification limits of the tricyclic antidepressants were 0.5-2.0 ng mL(-1) and 2.0-5.0 ng mL(-1), respectively. The average recoveries of TCAs were 88.2-104.3%. Moreover, the inter- and intra-day precision and accuracy was acceptable at all concentrations. The results showed that DLLME is applicable to the determination of trace amounts of TCAs in human urine sample. PMID- 22035982 TI - Extreme exercise enhances chromogranin A levels correlating with stress levels but not with cardiac burden. AB - OBJECTIVE: Stress and heart failure are associated with increased systemic levels of chromogranin A (CGA). Here we analyzed the effects of marathon running on systemic CGA levels and the association with cardiac burden and stress. METHODS: We recruited 47 lean and obese runners for a 10week training program aiming at running a marathon. Heart rates, individual fitness and marathon finishing times were monitored. CGA, proBNP and troponin T levels were analyzed by ELISA. RESULTS: We found a significant increase of CGA (+51%; p<0.01) in lean runners after marathon. The obese group showed the highest troponin T (0.22ng/ml; p<0.01) and proBNP (176.6ng/ml; p<0.01) levels. There were no correlations between proBNP, troponin T and CGA. An inverse correlation (r=-0.45; p<0.01) was found between CGA and finishing times. CONCLUSION: Marathon running is associated with increased CGA levels. However, this does not seem to reflect cardiac burden but rather marathon induced stress. PMID- 22035984 TI - Surface characterization of feldspathic ceramic using ATR FT-IR and ellipsometry after various silanization protocols. AB - OBJECTIVES: This study characterized the feldspathic ceramic surfaces after various silanization protocols. METHODS: Ceramic bars (2 mm * 4 mm * 10 mm) (N = 18) of feldpathic ceramic (VM7, VITA Zahnfabrik) were manufactured and finished. Before silane application, the specimens were ultrasonically cleaned in distilled water for 10 min. The ceramic specimens were randomly divided into nine groups (N = 2 per group) and were treated with different silane protocols. MPS silane (ESPE Sil, 3M ESPE) was applied to all specimens and left to react at 20 degrees C for 2 min (G20). After drying, the specimens were subjected to heat treatment in an oven at 38 degrees C (G38), 79 degrees C (G79) or 100 degrees C (G100) for 1 min. Half of the specimens of each group were rinsed with water at 80 degrees C for 15s (G20B, G38B, G79B, G100B). The control group (GC) received no silane. Attenuated total reflection infrared Fourier transform analysis (ATR FT-IR) was performed using a spectrometer. Thickness of silane layer was measured using a spectroscopic ellipsometer working in the lambda = 632.8 nm (He-Ne laser) at 70 degrees incidence angle. Surface roughness was evaluated using an optical profilometer. Specimens were further analyzed under the Scanning Electron Microscopy (SEM) to observe the topographic patterns. RESULTS: ATR FT-IR analysis showed changes in Si-O peaks with enlarged bands around 940 cm(-1). Ellipsometry measurements showed that all post-heat treatment actions reduced the silane film thickness (30.8-33.5 nm) compared to G20 (40 nm). The groups submitted to rinsing in hot water (B groups) showed thinner silane films (9.8-14.4 nm) than those of their corresponding groups (without washing) (30.8-40 nm). Profilometer analysis showed that heat treatments (Ra ~ 0.10-0.19 MUm; Rq ~ 0.15-0.26 MUm) provided a smoother surface than the control group (Ra ~ 0.48 MUm; Rq ~ 0.65 MUm). Similar patterns were also observed in SEM images. SIGNIFICANCE: Heat treatment after MPS silane application improved the silane layer network. Rinsing with boiling water eliminated the outmost unreacted regions of the silane yielding to thinner film thicknesses. PMID- 22035983 TI - Synthesis and characterization of dimethacrylates containing quaternary ammonium functionalities for dental applications. AB - OBJECTIVES: The widespread incidence of recurrent caries highlights the need for improved dental restorative materials. The objective of this study was to synthesize low viscosity ionic dimethacrylate monomers (IDMAs) that contain quaternary ammoniums groups (antimicrobial functionalities) and are compatible with existing dental dimethacrylate-based monomers. Such monomers have the potential to copolymerize with other methacrylate monomers and produce antibacterial polymers. METHODS: Two monomers (IDMA-1 and IDMA-2) were synthesized using the Menschutkin reaction and incorporated at 0-30% (by mass) into a 1:1 (by mass) bisphenol A glycerolate dimethacrylate (BisGMA):triethylene glycol dimethacrylate (TEGDMA) resin. Resin viscosity was quantified using rheology, and polymer degree of conversion (DC) and surface charge density were measured using Fourier transform infrared spectroscopy (FTIR) and fluorescein binding, respectively. Effects of IDMA-1 on initial attachment of Streptococcus mutans and on viability and metabolic activity (via reductase enzymes) of RAW 264.7 macrophage-like cells were quantified. RESULTS: IDMA-1 and IDMA-2 were prepared and characterized. IDMA-1 was miscible with BisGMA:TEGDMA and slightly increased the resin viscosity and DC. As expected, polymeric surface charge density increased with increasing IDMA-1. Incorporation of 10% IDMA-1 into BisGMA:TEGDMA reduced bacterial colonization without affecting viability or metabolic activity of mammalian cells. Increasing IDMA-1 up to 30% had no additional effect on bacterial coverage, but >=20% IDMA-1 significantly reduced macrophage density, viability, and metabolic activity. Leachables from polymers containing IDMA-1 were not cytotoxic. SIGNIFICANCE: The Menschutkin reaction provides a facile, convenient means to synthesize new monomers with quaternary ammonium groups for dental and medical applications. PMID- 22035985 TI - Descriptive analysis of the verbal behavior of a therapist: a known-group validity analysis of the putative behavioral functions involved in clinical interaction. AB - This study analyzes the interobserver agreement and hypothesis-based known-group validity of the Therapist's Verbal Behavior Category System (SISC-INTER). The SISC-INTER is a behavioral observation protocol comprised of a set of verbal categories representing putative behavioral functions of the in-session verbal behavior of a therapist (e.g., discriminative, reinforcing, punishing, and motivational operations). The complete therapeutic process of a clinical case of an individual with marital problems was recorded (10 sessions, 8 hours), and data were arranged in a temporal sequence using 10-min periods. Hypotheses based on the expected performance of the putative behavioral functions portrayed by the SISC-INTER codes across prevalent clinical activities (i.e., assessing, explaining, Socratic method, providing clinical guidance) were tested using autoregressive integrated moving average (ARIMA) models. Known-group validity analyses provided support to all hypotheses. The SISC-INTER may be a useful tool to describe therapist-client interaction in operant terms. The utility of reliable and valid protocols for the descriptive analysis of clinical practice in terms of verbal behavior is discussed. PMID- 22035986 TI - A randomized clinical trial comparing affect regulation and social problem solving psychotherapies for mothers with victimization-related PTSD. AB - Addressing affect dysregulation may provide a complementary alternative or adjunctive approach to the empirically supported trauma memory processing models of cognitive behavior therapy (CBT) for posttraumatic stress disorder (PTSD). A CBT designed to enhance affect regulation without trauma memory processing- trauma affect regulation: guide for education and therapy (TARGET)--was compared to present centered therapy (PCT) and wait-list (WL) conditions in a randomized clinical trial with 146 primarily low-income and ethnoracial minority mothers with PTSD. TARGET achieved statistically and clinically significant improvement on PTSD and affect regulation measures compared to WL, with more consistent and sustained (over a 6-month follow-up period) evidence of improvement than PCT. Drop-out rates (~25%) were comparable in TARGET and PCT, similar to those previously reported for trauma memory processing CBTs. Symptom worsening was rare (2-8%) and transient. Affect regulation-based CBT without trauma memory processing warrants further research as a potentially efficacious therapy for victimization-related PTSD. PMID- 22035987 TI - Changes in ecological momentary assessment reported affect associated with episodes of nonsuicidal self-injury. AB - Although emotion regulation deficits have been frequently implicated in the incidence of nonsuicidal self-injurious behavior (NSSI), no research to date has examined in vivo change of affect associated with real-world NSSI behavior. The present study employed Ecological Momentary Assessment (EMA) to assess change in affect associated with episodes of experienced NSSI in a sample of 36 college students with a self-reported history of NSSI. Results indicated that individuals who reported NSSI behavior over the course of the study experienced increases in negative affect prior to an episode of NSSI that peaked during the episode and faded gradually in the hours following the episode, with affect change roughly approximating a quadratic curve. These changes in affect were detected only at times in which individuals engaged in NSSI and were absent for individuals who did not report NSSI over the course of the study. Moreover, changes in negative affect associated with NSSI were, on average, detectable hours prior to the NSSI event. These findings suggest that episodes of NSSI may be predicted through a careful examination of affect change long before actual NSSI behavior occurs. PMID- 22035988 TI - A pilot study of the DBT coach: an interactive mobile phone application for individuals with borderline personality disorder and substance use disorder. AB - Dialectical behavior therapy (DBT) has received strong empirical support and is practiced widely as a treatment for borderline personality disorder (BPD) and BPD with comorbid substance use disorders (BPD-SUD). Therapeutic success in DBT requires that individuals generalize newly acquired skills to their natural environment. However, there have been only a limited number of options available to achieve this end. The primary goal of this research was to develop and test the feasibility of the DBT Coach, a software application for a smartphone, designed specifically to enhance generalization of a specific DBT skill (opposite action) among individuals with BPD-SUD. We conducted a quasiexperimental study in which 22 individuals who were enrolled in DBT treatment programs received a smartphone with the DBT Coach for 10 to 14 days and were instructed to use it as needed. Participants used the DBT Coach an average of nearly 15 times and gave high ratings of helpfulness and usability. Results indicate that both emotion intensity and urges to use substances significantly decreased within each coaching session. Furthermore, over the trial period, participants reported a decrease in depression and general distress. Mobile technology offering in vivo skills coaching may be a useful tool for reducing urges to use substances and engage in other maladaptive behavior by directly teaching and coaching in alternative, adaptive coping behavior. PMID- 22035989 TI - Global and local evaluations of public speaking performance in social anxiety. AB - Differences in the relative use of global and local information (seeing the forest vs. the trees) may explain why people with social anxiety often do not benefit from corrective feedback, even though they pay close attention to details in social situations. In the current study, participants high (n=43) or low (n=47) in social anxiety symptoms gave a series of brief speeches, and then self rated their speaking performance on items reflecting global and local performance indicators (self-assessment) and also received standardized performance feedback from an experimenter. Participants then completed a questionnaire asking how they thought the experimenter would rate their performance based on the feedback provided (experimenter assessment). Participants completed the self- and experimenter assessments again after 3 days, in addition to a measure of postevent processing (repetitive negative thinking) about their speech performance. Results showed that, as hypothesized, the High SA group rated their performance more negatively than the Low SA group. Moreover, the High SA group's ratings of global aspects of their performance became relatively more negative over time, compared to their ratings of local aspects and the Low SA group's ratings. As expected, postevent processing mediated the relationship between social anxiety group status and worsening global performance evaluations. These findings point to a pattern of progressively more negative global evaluations over time for persons high in social anxiety. PMID- 22035990 TI - Cognitive behavioral therapy in practice: treatment delivered by trainees at an outpatient clinic is clinically effective. AB - Cognitive-behavioral therapy (CBT) is known to be effective for a number of disorders, and can be delivered effectively by trainees in controlled settings. However, the effectiveness of trainee therapists in general practice compared to that of more experienced therapists is unknown. In this study, the authors used a benchmarking strategy to compare the outcomes of naturalistic CBT delivered by trainee therapists to those of efficacy and effectiveness studies using primarily professional therapists. Patients (N=249) with mood and anxiety disorders were treated by trainees (primarily by interns and postdocs) using nonstandardized nonmanualized CBT at an outpatient clinic in an urban academic medical center. Changes in anxiety and depression were assessed using effect sizes, reliable and clinically significant change, and benchmarked to efficacy and effectiveness studies. Symptoms of anxiety and depression significantly improved from start to end of treatment. Rates of improvement and recovery compared favorably to those achieved in other studies, with the exception of recovery rates in severe depression. Effect sizes were in the medium to large range, but generally lower than those achieved in other studies. Results suggest that CBT can be delivered effectively by trainees in an outpatient setting. PMID- 22035991 TI - Modular cognitive-behavioral therapy for body dysmorphic disorder. AB - This study pilot tested a newly developed modular cognitive-behavioral therapy (CBT) treatment manual for body dysmorphic disorder (BDD). We tested feasibility, acceptability, and treatment outcome in a sample of 12 adults with primary BDD. Treatment was delivered in weekly individual sessions over 18 or 22 weeks. Standardized clinician ratings and self-report measures were used to assess BDD and related symptoms pre- and posttreatment and at 3- and 6-month follow-ups. At posttreatment, BDD and related symptoms (e.g., mood) were significantly improved. Treatment gains were maintained at follow-up. A relatively low drop-out rate, high patient satisfaction ratings, and patient feedback indicated that the treatment was highly acceptable to patients. To our knowledge, this represents the first test of a broadly applicable, individual psychosocial treatment for BDD. PMID- 22035992 TI - Popular or unpopular? Therapists' use of structured interviews and their estimation of patient acceptance. AB - An accurate diagnosis is an important precondition for effective psychotherapeutic treatment. The use of structured interviews provides the gold standard for reliable diagnosis. Suppiger et al. (2009) showed that structured interviews have a high acceptance among patients. On a scale from 0 (not at all satisfied) to 100 (totally satisfied) patients rated overall satisfaction with a structured interview at M=86.55. Nevertheless, therapists rarely seem to use structured interviews in clinical practice. The aim of this study was to assess how frequently therapists use structured interviews in daily practice. Secondly, we hypothesized that therapists underestimate patient acceptance of structured interviews. As a third goal, we explored further reasons why therapists choose not to use structured interviews. We conducted an online survey of 1,927 psychiatrists and psychotherapists in Switzerland and asked them how frequently they used structured interviews and how they estimated patient satisfaction with these interviews. Furthermore, we asked therapists why they chose to use or not use structured interviews. Therapists reported using structured interviews on average with about 15% of their patients. Furthermore, therapists estimated significantly lower patient acceptance than patients themselves indicated (M(therapist)=49.41, M(patient)=86.55). Our data suggest lack of familiarity with these instruments as well as an overestimation of the utility of open clinical interviews as further reasons for not using structured interviews. PMID- 22035993 TI - Rethinking safety behaviors in insomnia: examining the perceived utility of sleep related safety behaviors. AB - Harvey's cognitive model of insomnia (2002a) proposes that sleep-related safety behaviors play a central role in the maintenance of insomnia because such maladaptive coping strategies are thought to reinforce threat-based appraisals of the likelihood and consequences of poor sleep. Research to date has assessed the frequency of safety behavior use in those with insomnia only; however, in addition to the frequency of occurrence, the function of safety behaviors (i.e., a belief that they will prevent a feared outcome from occurring), may be an important consideration. The purpose of this study was to examine sleep-related safety behaviors based on an expanded theoretical understanding of such behaviors across psychological disorders; that is, by examining both their frequency and perceived utility. Undergraduate students (N=376) completed an online survey about their sleep, mood, and use of sleep-related safety behaviors. Insomnia severity was associated with a greater perceived need to use safety behaviors (i.e., utility) but not with frequency of safety behavior use. Higher perceived utility of safety behaviors was also associated with unhelpful beliefs about sleep, fear and avoidance of fatigue, and both general and sleep-specific helplessness. These results suggest that these behaviors and the associated underlying maladaptive beliefs may be important targets in cognitive behavioral therapy for insomnia. The current study extends the existing literature and refines the concept of safety behaviors in insomnia to include both the function and frequency of these behaviors. PMID- 22035994 TI - Attributions for spousal behavior in relation to criticism and perceived criticism. AB - This study examined relations between spousal attributions and criticism in a sample of 118 married couples. Spouses rated general perceived criticism (PC) and their own expressed criticism as well as interaction-specific PC from a videotaped discussion. Independent judges also coded criticism from the discussion. Spouses' self-reported causal and responsibility attributions for hypothetical spousal negative behavior were related to all types of criticism. Attributions were also associated with unique variance in spouses' reports of general PC and criticism, even after controlling either for judges' or partners' ratings of criticism and marital adjustment. General PC and expressed criticism appear to reflect more than either the amount of criticism present or feelings about the marriage; rather, general PC and expressed criticism are uniquely associated with the cause and responsibility ascribed to partners' behavior. PMID- 22035995 TI - Motion as motivation: using repetitive flexion movements to stimulate the approach system. AB - Research suggests that having a healthy approach system is critical for adaptive emotional functioning. The goal of the current study (n=186 undergraduates) was to determine the efficacy of an easy-to-disseminate and cost-efficient strategy for stimulating this system. The experiment tested the effects of repeated flexion movements (rFM) on approach system activation as measured by both self report (BAS scales) and behavior. The results showed that rFM increased approach system motivation in men but not women. Men who completed the rFM task reported significantly greater levels of fun-seeking motivation than men in the control task. Moreover, the rFM task led to changes in actual behavior. Men who completed the rFM task exhibited significantly greater persistence on a difficult laboratory task than men in the control task. In contrast, women who completed the rFM task reported significantly lower levels of fun seeking and tended to exhibit less persistence on a difficult laboratory task than women in the control task. These results provide support for embodied theories of emotion as well as additional evidence for a gender difference in approach-avoidance tendencies. PMID- 22035996 TI - Preliminary psychometric properties of the Acceptance and Action Questionnaire II: a revised measure of psychological inflexibility and experiential avoidance. AB - The present research describes the development and psychometric evaluation of a second version of the Acceptance and Action Questionnaire (AAQ-II), which assesses the construct referred to as, variously, acceptance, experiential avoidance, and psychological inflexibility. Results from 2,816 participants across six samples indicate the satisfactory structure, reliability, and validity of this measure. For example, the mean alpha coefficient is .84 (.78-.88), and the 3- and 12-month test-retest reliability is .81 and .79, respectively. Results indicate that AAQ-II scores concurrently, longitudinally, and incrementally predict a range of outcomes, from mental health to work absence rates, that are consistent with its underlying theory. The AAQ-II also demonstrates appropriate discriminant validity. The AAQ-II appears to measure the same concept as the AAQ I (r=.97) but with better psychometric consistency. PMID- 22035997 TI - Psychometric properties of the mobility inventory for agoraphobia: convergent, discriminant, and criterion-related validity. AB - Aims of this study were (a) to summarize the psychometric literature on the Mobility Inventory for Agoraphobia (MIA), (b) to examine the convergent and discriminant validity of the MIA's Avoidance Alone and Avoidance Accompanied rating scales relative to clinical severity ratings of anxiety disorders from the Anxiety Disorders Interview Schedule (ADIS), and (c) to establish a cutoff score indicative of interviewers' diagnosis of agoraphobia for the Avoidance Alone scale. A meta-analytic synthesis of 10 published studies yielded positive evidence for internal consistency and convergent and discriminant validity of the scales. Participants in the present study were 129 people with a diagnosis of panic disorder. Internal consistency was excellent for this sample, alpha=.95 for AAC and .96 for AAL. When the MIA scales were correlated with interviewer ratings, evidence for convergent and discriminant validity for AAL was strong (convergent r with agoraphobia severity ratings=.63 vs. discriminant rs of .10 .29 for other anxiety disorders) and more modest but still positive for AAC (.54 vs. .01-.37). Receiver operating curve analysis indicated that the optimal operating point for AAL as an indicator of ADIS agoraphobia diagnosis was 1.61, which yielded sensitivity of .87 and specificity of .73. PMID- 22035998 TI - Does acceptance and relationship focused behavior therapy contribute to bupropion outcomes? A randomized controlled trial of functional analytic psychotherapy and acceptance and commitment therapy for smoking cessation. AB - This study evaluated a treatment combining bupropion with a novel acceptance and relationship focused behavioral intervention based on the acceptance and relationship context (ARC) model. Three hundred and three smokers from a community sample were randomly assigned to bupropion, a widely used smoking cessation medication, or bupropion plus functional analytic psychotherapy (FAP) and acceptance and commitment therapy (ACT). Objective measures of smoking outcomes and self-report measures of acceptance and relationship processes were taken at pretreatment, posttreatment, 6-month, and 1-year follow-up. The combined treatment was significantly better than bupropion alone at 1-year follow-up with 7-day point prevalence quit rates of 31.6% in the combined condition versus 17.5% in the medication-alone condition. Acceptance and the therapeutic relationship at posttreatment statistically mediated 12-month outcomes. Bupropion outcomes were enhanced with an acceptance and relationship focused behavioral treatment. PMID- 22035999 TI - Predicting premature termination within a randomized controlled trial for binge eating patients. AB - Understanding the dropout rates of efficacious forms of psychotherapy for patients with binge eating disorder (BED) is an unsolved problem within this increasing population. Up until now the role of psychotherapy process characteristics as predictors of premature termination has not been investigated in the BED literature. Within a randomized controlled trial (N=78) we investigated the degree to which early psychological process characteristics, such as components of the therapeutic relationship and the experiences of mastery and motivational clarification, predicted premature termination of treatment. We statistically controlled for the influences of covariates such as rapid response of treatment, treatment group, body mass index, Axis II disorder, and patients' preexisting generalized self-efficacy at baseline. Patients' postsession reports from Sessions 1 to 5 indicated that low self-esteem in-session experiences was a stable predictor of premature termination. Its predictive value persisted after controlling for the above-mentioned covariates. Exploratory analyses further revealed low self-esteem experiences, low global alliance, and low mastery and clarification experiences as predictors in those patients who explicitly specified discontentment with therapy as reason for premature termination. These results indicate that patients' self-esteem experiences may not be an epiphenomenon of their specific psychopathology but may represent general mechanisms on which remaining or withdrawing from psychotherapeutic treatment depends. Early psychotherapy process characteristics should therefore be considered in training and evaluation of psychotherapists carrying through BED treatments. PMID- 22036000 TI - The behavioral activation for depression scale-short form: development and validation. AB - Following a landmark component analysis of cognitive therapy by Jacobson and colleagues (1996), there has been renewed interest in behavioral activation (BA) treatments for depression. The Behavioral Activation for Depression Scale (BADS) was developed to measure when and how clients become activated over the course of BA treatment. Multiple studies have provided initial support for the BADS but have also identified several potential problems. Four studies were conducted in order to develop and provide initial evaluation of a short form of the BADS that addresses these concerns. In Study 1, an exploratory factor analysis was conducted on existing data using the original BADS in order to identify items to retain for the short form. In Study 2, these items were administered to a new sample of college students with elevated depressive symptoms and were analyzed with exploratory and confirmatory factor analyses. Study 3 examined the predictive validity of the BADS-SF by examining the BADS-SF and depression scores in relation to activity tracking and reward-value ratings over the course of 1 week. Study 4 examined BADS-SF data over the course of BA treatment for two clients using cross-lagged panel correlations. With one client, changes in BADS SF scores led changes in depression scores by 1 week, whereas with the other client changes in BADS-SF and depression scores occurred concurrently. These studies resulted in a nine-item scale that demonstrated good item characteristics as well as acceptable internal consistency reliability, construct validity, and predictive validity. PMID- 22036001 TI - Exploring negative emotion in women experiencing intimate partner violence: shame, guilt, and PTSD. AB - This study explored the association of shame and guilt with PTSD among women who had experienced intimate partner violence (IPV). Sixty-three women were assessed by a research clinic serving the mental health needs of women IPV survivors. Results indicated that shame, guilt-related distress, and guilt-related cognitions showed significant associations with PTSD but global guilt did not. When shame and guilt were examined in the context of specific forms of psychological abuse, moderation analyses indicated that high levels of both emotional/verbal abuse and dominance/isolation interacted with high levels of shame in their association with PTSD. Neither guilt-related distress nor guilt related cognitions were moderated by specific forms of psychological abuse in their association with PTSD. These data support the conceptualization of shame, guilt distress, and guilt cognitions as relevant features of PTSD. Results are discussed in light of proposed changes to diagnostic criteria for PTSD. PMID- 22036002 TI - Prospective prediction of nonsuicidal self-injury: a 1-year longitudinal study in young adults. AB - Nonsuicidal self-injury (NSSI) has become a significant public health problem. Although numerous studies have examined cross-sectional psychological correlates of NSSI, there has been little research examining predictors of NSSI over time. The present study examined cross-sectional and longitudinal correlates of NSSI in 81 young adult self-injurers (M age=19, 74.1% female, 51.9% Caucasian), 51 of whom were followed up 1 year later. At baseline, participants completed self report measures of NSSI, Axis-I disorders, borderline personality disorder (BPD), and impulsivity, as well as an implicit measure of NSSI attitudes and identity. One year later, participants completed a Timeline Followback Method whereby they indicated their engagement in NSSI over the previous 12 months. Analyses replicated many known cross-sectional correlates of NSSI, including symptoms of several Axis-I disorders and BPD. However, many of these same variables failed to predict the course of NSSI over the 1-year follow-up. The only variables to prospectively predict NSSI were past NSSI (i.e., frequency, methods, and recency of NSSI), participants' behavioral forecast of their engagement in future NSSI, and BPD features. Findings suggest that many cross-sectional correlates of NSSI may not be useful for predicting subsequent NSSI. Instead, NSSI severity and BPD features appear to best predict continued engagement in NSSI. PMID- 22036003 TI - Comparison of DFT methods for molecular structure and vibration spectra of ofloxacin calculations. AB - Comparison of the performance of different density functional theory (DFT) methods at various basis sets in predicting molecular and vibration spectra of ofloxacin was reported. The methods employed in this study comprise six functionals, namely, mPW1PW91, HCTH, LSDA, PBEPBE, B3PW91 and B3LYP. Different basis sets including LANL2DZ, SDD, LANL2MB, 6-31g, 6-311g and 3-21g were also examined. Comparison between the calculated and experimental data indicates that the mPW1PW91/6-311g level afford the best quality to predict the structure of ofloxacin. The results also indicate that B3LYP/LANL2DZ level show better performance in the vibration spectra prediction of ofloxacin than other DFT methods. PMID- 22036004 TI - Determination of phenol by flow-injection with chemiluminescence detection based on the hemin-catalysed luminol-hydrogen peroxide reaction. AB - This study established a novel flow injection (FI) methodology for the determination of phenol in aqueous samples based on luminol chemiluminescence (CL) detection. The method was based on the inhibition that phenol caused on the hemin-catalysed chemiluminescence reaction between luminol and hydrogen peroxide in alkaline solution. Optimum conditions and possible mechanisms have been investigated. The linear range was 2.0*10(-9) to 4.0*10(-7)gmL(-1) for phenol. The proposed method is sensitive with a detection limit of 4.0*10(-10)gmL(-1). The relative standard deviation for 11 measurements was 2.3% for 1.0*10(-7)gmL( 1) phenol. The method was applied for the determination of phenol in waste water samples. The results obtained compared well with those by an official method. PMID- 22036005 TI - A structural and spectroscopic study on para-aminohippuric acid with experimental and theoretical approaches. AB - In this work, the molecular conformation, vibrational and electronic analysis of para-aminohippuric acid (pAHA, C(9)H(10)N(2)O(3)) were presented for the ground state using experimental techniques (FT-IR, FT-Raman and UV) and density functional theory (DFT) employing B3LYP exchange correlation with the 6 311++G(d,p) basis set. FT-IR and FT-Raman spectra were recorded in the regions of 400-4000cm(-1) and 50-4000cm(-1), respectively. The UV absorption spectra of the compound that dissolved in ethanol and water solution were recorded in the range of 190-400nm. Potential energy curve was computed by means of scanning NCCO torsion angle. The geometry optimization and the energies associated possible four conformers (C1-C4) were computed. The computational results diagnose the most stable conformer of pAHA as the C1 form. Optimized structure of compound was interpreted and compared with the earlier reported experimental values. The complete assignments of fundamental vibrations were performed on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method. A study on the electronic properties, such as frontier molecular energies, absorption wavelengths and oscillator strengths, were predicted by time-dependent DFT (TD-DFT) approach, while taking solvent effects into account. To investigate non-linear optical properties: polarizability, anisotropy of polarizability and molecular first hyperpolarizability of molecule were computed. Thermodynamic properties (heat capacity, entropy and enthalpy) of the title compound at different temperatures were calculated. PMID- 22036006 TI - Obsessive-compulsive symptoms in schizophrenia: implications for future psychiatric classifications. AB - Although obsessive-compulsive symptoms are not considered primary features, they are prevalent, independent of psychosis, and substantially modify clinical characteristics, course, treatment and prognosis of schizophrenia. The authors highlight the clinical significance of obsessive-compulsive symptoms in schizophrenia, provide diagnostic criteria for "schizo-obsessive" patients and address future directions for research. PMID- 22036007 TI - Validation and normalization of the General Health Questionnaire 30 in parents with primary school children in China. AB - OBJECTIVES: Parenting can be a stressful experience. Higher levels of parenting stress are predictive of parents' negative appraisal of children's behavior, the use of physical discipline, and poor child outcomes across a variety of domains. Assessment of parenting depression is needed in China. This study aims to standardize the Chinese version of the General Health Questionnaire (GHQ-30) for parents of primary school children. METHOD: Stratified randomly selected parents of primary school children were selected from the cities of Nanjing and Shenyang in China. The Chinese version of the General Health Questionnaire 30 was administered to 7615 parents of primary school students aged between 8 and 12 years. A high response rate was achieved, with 6672 parents (88%) responding to the survey. RESULTS: Exploratory factor analysis with a 5-factor solution showed that 5 factors were extracted from the scale, namely, depression, anxiety, inadequate coping, social dysfunctioning, and sleep disturbance. The 5-factor structures were confirmed by using confirmatory factor analysis (CFA). Overall, the 5-factor structure had a high level of reliability for each individual dimension. Confirmatory factor analysis showed that the 5-factor structure abstracted from this study had a good model fit. CONCLUSIONS: The 5-factor structure derived from the present sample of parents, with good model fit in the CFA analysis, suggests that a 5-factor solution can be used to assess parent psychopathological symptoms in mainland Chinese parents of primary school children. PMID- 22036008 TI - WITHDRAWN: Anatomic differences in first episode schizophrenia: a deformation based morphometry MRI Study. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 22036009 TI - Validation of a short French version of the UPPS-P Impulsive Behavior Scale. AB - BACKGROUND: Impulsivity is a multifaceted construct that has a prominent role in psychiatry. Lynam et al (2006) have developed the UPPS-P, a 59-item scale measuring 5 impulsivity components: negative urgency, positive urgency, lack of premeditation, lack of perseverance, and sensation seeking. The aim of the present study was to validate a short, 20-item French version of the UPPS-P. METHODS: Six hundred fifty participants filled out the short French UPPS-P. A subgroup of participants (n = 145) took part in a follow-up study and completed the scale twice to determine test-retest stability; another subgroup (n = 105) was screened with other questionnaires also to establish external validity. RESULTS: Confirmatory factor analyses supported a hierarchical model comprising 2 higher order factors of urgency (resulting from negative urgency and positive urgency) and lack of conscientiousness (resulting from lack of premeditation and lack of perseverance) as well as a separate factor of sensation seeking. The results indicated good internal consistency and test-retest stability. External validity was supported by relationships with psychopathological symptoms. CONCLUSION: The short French version of the UPPS-P therefore presents good psychometric properties and may be considered a promising instrument for both research and clinical practice. PMID- 22036010 TI - Insight, symptomatic dimensions, and cognition in patients with acute-phase psychosis. AB - AIMS: This study was designed to evaluate the relationship between insight and the severity of psychotic symptomatology in a sample of patients in an acute phase of psychosis, as well as to analyze the relationship between insight and the symptomatic profile of the patient. In addition, the role of general cognitive abilities in this relationship was explored. METHOD: Cross-sectional observational study of 96 acute psychotic adults. To evaluate psychopathology we used the Positive and Negative Syndrome Scale; for insight, the Scale of Unawareness of Mental Disorder; and for general cognitive abilities, the Screen for Cognitive Impairment in Psychiatry. RESULTS: Insight showed significant and moderate positive correlations with positive and general symptoms but not with negative symptoms. In the subgroup with positive symptomatic profile, awareness of the disorder and of the effects of medication were positively associated with severity of positive and general psychotic symptoms. Awareness of social consequences of the disease was positively associated with positive symptoms. In the subgroup with a negative symptomatic profile, awareness of the disorder and of the effects of medication were positively associated with severity of positive and general psychotic symptoms. In this subgroup, these relationships were significantly affected by general cognitive abilities. CONCLUSIONS: Insight was not related with the severity of negative psychotic symptoms. The symptomatic profile of subjects played an important role in determining the relationship between insight and its dimensions and the severity of psychotic symptoms. Cognitive function moderated these relationships only in the negative symptomatic profile. PMID- 22036011 TI - Stigma: a core factor on predicting functionality in bipolar disorder. AB - OBJECTIVE: Extant literature indicates that bipolar disorder (BD) is associated with significant poor psychosocial functioning. However, the relationship between functioning and demographic and clinical variables is unclear. The aim of this study is to investigate the predictors of functioning such as demographic and clinical variables, social support, self-perceived stigma, and insight in remitted patients with BD. METHODS: Eighty patients with a diagnosis of BD, complete remission according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were included in the final assessment. Bipolar Disorder Functioning Questionnaire, Beck Depression Inventory, Young Mania Rating Scale, Internalized Stigma of Mental Illness Scale, Multidimensional Scale of Perceived Social Support, and Schedule for Assessing the Three Components of Insight were used. Student t test, Pearson correlation analyses, and linear regression analyses were used to assess the pathways effecting on functioning. RESULTS: The 3 predictors of functioning were severity of depression, perceived social support, and internalized stigmatization. Severity of depression is considered the strongest predictor, whereas internalized stigmatization has a core role in predicting functioning. Clinical variables such as years of education and number of hospitalization probably have indirect effects on functioning. CONCLUSION: Interventions that oppose stigmatization and consideration of mild depressive symptoms will positively affect functioning in remitted patients with BD. PMID- 22036012 TI - Genotoxic and enzymatic effects of fluoranthene in microsomes and freshly isolated hepatocytes from sole (Solea solea). AB - The fluoranthene (Fluo) is one of the most abundant polycyclic aromatic hydrocarbons (PAHs) in human food and in marine compartments. However, the existing data on its genotoxicity is poor and controversial. The aim of this study was to assess in vitro the potential genotoxicity of Fluo in sole and its possible effect on CYP450 modulation. Freshly isolated hepatocytes were exposed for 24 h to a range of Fluo concentrations from 0.5 to 50 MUM in both culture flasks and microplate wells. The ethoxyresorufin-O-deethylase (EROD) activity was measured as an indicator of the activity of the cytochrome P450 1A1 (CYP1A1). The genotoxic effects were evaluated by measuring both DNA strand breaks and DNA adducts by the alkaline comet assay and the postlabeling technique respectively. Calf thymus DNA was also exposed to Fluo in the presence of sole liver microsomes in order to check for Fluo DNA adduct formation. In sole hepatocytes, Fluo was shown to induce a decrease in the EROD activity in a concentration-dependent manner. A significant genotoxic effect was observed in terms of DNA strand breakage from an exposure concentration of 5 MUM: despite a concentration dependent effect was observed, it did not follow a linear dose-response. The response was similar whatever the way of exposure in flasks or in wells. One reproducible adduct was detected in the hepatocytes exposed to the highest concentrations of Fluo. The formation of Fluo adducts was confirmed by the detection of one reproducible adduct following in vitro exposure of calf thymus DNA to 100 and 200 MUM of Fluo in the presence of sole microsomes. These results demonstrate the potential of sole hepatocytes to metabolize Fluo in 24 h into reactive species, able to induce genotoxicity by DNA strand breakage and DNA adduct formation. Moreover, a miniaturized cell exposure system was validated for further experiments using fewer amounts of hepatocytes and contaminants, and allowing exposure to PAH metabolites. PMID- 22036014 TI - Type-2 fuzzy model based controller design for neutralization processes. AB - In this study, an inverse controller based on a type-2 fuzzy model control design strategy is introduced and this main controller is embedded within an internal model control structure. Then, the overall proposed control structure is implemented in a pH neutralization experimental setup. The inverse fuzzy control signal generation is handled as an optimization problem and solved at each sampling time in an online manner. Although, inverse fuzzy model controllers may produce perfect control in perfect model match case and/or non-existence of disturbances, this open loop control would not be sufficient in the case of modeling mismatches or disturbances. Therefore, an internal model control structure is proposed to compensate these errors in order to overcome this deficiency where the basic controller is an inverse type-2 fuzzy model. This feature improves the closed-loop performance to disturbance rejection as shown through the real-time control of the pH neutralization process. Experimental results demonstrate the superiority of the inverse type-2 fuzzy model controller structure compared to the inverse type-1 fuzzy model controller and conventional control structures. PMID- 22036013 TI - Antioxidant deficit in gills of Pacific oyster (Crassostrea gigas) exposed to chlorodinitrobenzene increases menadione toxicity. AB - Disturbances in antioxidant defenses decrease cellular protection against oxidative stress and jeopardize cellular homeostasis. To knock down the antioxidant defenses of Pacific oyster Crassostrea gigas, animals were pre treated with 1-chloro-2,4-dinitrobenzene (CDNB) and further challenged with pro oxidant menadione (MEN). CDNB pre-treatment (10 MUM for 18 h) was able to consume cellular thiols in gills, decreasing GSH (53%) and decrease protein thiols (25%). CDNB pre-treatment also disrupted glutathione reductase and thioredoxin reductase activity in the gills, but likewise strongly induced glutathione S-transferase activity (270% increase). Surprisingly, hemocyte viability was greatly affected 24 h after CDNB removal, indicating a possible vulnerability of the oyster immune system to electrophilic attack. New in vivo approaches were established, allowing the identification of higher rates of GSH-CDNB conjugate export to the seawater and enabling the measurement of the organic peroxide consumption rate. CDNB induced impairment in antioxidant defenses decreased the peroxide removal rate from seawater. After showing that CDNB decreased gill antioxidant defenses and increased DNA damage in hemocytes, oysters were further challenged with 1 mM MEN over 24 h. MEN treatment did not affect thiol homeostasis in gills, while CDNB pre-treated animals recovered GSH and PSH to the control level after 24 h of depuration. Interestingly, MEN intensified GSH and PSH loss and mortality in CDNB pre-treated animals, showing a clear synergistic effect. The superoxide generating one-electron reduction of MEN was predominant in gills and may have contributed to MEN toxicity. These results support the idea that antioxidant depleted animals are more susceptible to oxidative attack, which can compromise survival. Data also corroborate the idea that gills are an important detoxifying organ, able to dispose of organic peroxides, induce phase II enzymes, and efficiently export GSH-CDNB conjugates. PMID- 22036015 TI - Photocatalytic degradation of bentazone in soil washing wastes containing alkylpolyoxyethylene surfactants. AB - Three alkylpolyoxyethylene surfactants bearing the same hydrophobic chain and a different number of oxyethylene groups were investigated as suitable candidates for the soil washing treatment of contaminated soil samples containing bentazone. Comparable good recoveries of the pesticide were obtained working with these surfactants. The photocatalytic treatment of the collected washing wastes, performed in the presence of suspended TiO(2) particles under irradiation with simulated sunlight, leads to the effective degradation of bentazone residues after a time depending on the nature and concentration of the chosen amphiphile. Brij 35 was found to be the best surfactant candidate, giving the faster abatement of the pesticide in the collected wastes. The overall treatment time depends on the bentazone mineralization kinetics, markedly slow in the presence of surfactants. Useful information about the photocatalytic degradation route was obtained from the HPLC-MS analysis of transient intermediates formed in water. PMID- 22036017 TI - Height and death in the Antebellum United States: A view through the lens of geographically weighted regression. AB - Factors related to geography such as climate, natural resources or waterways often affect human activities. However, traditional approaches such as ordinary least squares (OLS) have limitations in investigating such patterns. Unlike OLS regression, geographically weighted regression (GWR) allows the coefficients of explanatory variables to differ by locality by giving relatively more weight to geographically close observations. GWR depicts spatial patterns. This paper examines the pattern of height and crude death rate in the United States prior to the Civil War by this method. The GWR results show that access to water transportation increased mortality and decreased stature in the food exporting areas of the Midwest, and the opposite pattern appeared in the food importing areas of the Northeast. PMID- 22036016 TI - The role of glial cells in synapse elimination. AB - Excessive synapses generated during early development are eliminated extensively to form functionally mature neural circuits. Synapses in juvenile and mature brains are highly dynamic, and undergo remodeling processes through constant formation and elimination of dendritic spines. Although neural activity has been implicated in initiating the synapse elimination process cell-autonomously, the cellular and molecular mechanisms that transduce changes in correlated neural activity into structural changes in synapses are largely unknown. Recently, however, new findings provide evidence that in different species, glial cells, non-neuronal cell types in the nervous system are crucial in eliminating neural debris and unwanted synapses through phagocytosis. Glial cells not only clear fragmented axons and synaptic debris produced during synapse elimination, but also engulf unwanted synapses thereby actively promoting synapse elimination non cell autonomously. These new findings support the important role of glial cells in the formation and maintenance of functional neural circuits in development as well as in adult stages and neurodegenerative diseases. PMID- 22036018 TI - Aspirin and colorectal cancer prevention in Lynch syndrome. PMID- 22036020 TI - The Measure of Insight into Cognition: reliability and validity of clinician rated and self-report scales of neurocognitive insight for schizophrenia. AB - Poor insight into the neurocognitive deficits in schizophrenia-spectrum disorders may have significant clinical implications for treatment. The purpose of this study was to replicate and extend the psychometric findings initially reported on the Measure of Insight into Cognition Clinician-Rated (MIC-CR) and Self-Report (MIC-SR) which assess awareness, attribution, and frequency of neurocognitive deficits. Assessments conducted one week apart allowed for internal consistency, test-retest reliability, concurrent validity, and administration order effects to be determined. In this study sample (N=80), 73 demonstrated significant neurocognitive impairment, yet on the MIC-CR, the average awareness and attribution scores indicated only partial awareness and attribution of neurocognitive deficits. The average MIC-SR score indicated rare frequency of cognitive difficulty in everyday life. Cronbach's alphas for the MIC-CR (0.83) and MIC-SR (0.93) were consistent with the initial validation study; test-retest reliability for both MIC assessments was significant (p<0.001). In new analyses, concurrent validity was demonstrated by significant correlations between the MIC CR and MIC-SR in the first validation sample: r=-0.75 (p<0.001) and the current replication sample: r=-0.70 (p<0.001). Effect sizes were large when frequencies of neurocognitive complaints (MIC-SR) were compared between subjects with good versus poor awareness on the MIC-CR. Reliability and concurrent validity results were similar and significant regardless of order of MIC-CR and MIC-SR administration. The MIC-CR and MIC-SR are thus reliable and valid complementary instruments to assess neurocognitive insight in people with schizophrenia spectrum disorders. PMID- 22036019 TI - Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. AB - BACKGROUND: Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. METHODS: In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. RESULTS: 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55.7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0.63 (95% CI 0.35-1.13, p=0.12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0.56 (95% CI 0.32-0.99, p=0.05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0.41 (0.19-0.86, p=0.02) and an IRR of 0.37 (0.18-0.78, p=0.008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. INTERPRETATION: 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55.7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. FUNDING: European Union; Cancer Research UK; Bayer Corporation; National Starch and Chemical Co; UK Medical Research Council; Newcastle Hospitals trustees; Cancer Council of Victoria Australia; THRIPP South Africa; The Finnish Cancer Foundation; SIAK Switzerland; Bayer Pharma. PMID- 22036021 TI - [Analysis of the cost effectiveness of home-based phototherapy with narrow-band UV-B radiation compared with biological drugs for the treatment of moderate to severe psoriasis]. AB - BACKGROUND: Psoriasis is associated with high treatment costs due to the increasing use of biologic drugs. Phototherapy has been demonstrated to be safe and cost effective for the treatment of psoriasis, although it is limited by the requirement for patients to visit a hospital various times a week. OBJECTIVES: To evaluate the efficiency of home-based phototherapy with narrow-band UV-B radiation compared with biologic drugs for the treatment of moderate to severe psoriasis under normal practice conditions in our setting. METHODS: A retrospective cost-effectiveness study was undertaken in 12 patients with moderate to severe psoriasis. Half of the patients were treated with biologic drugs (2 with etanercept, 2 with adalimumab, and 2 with infliximab) and the other half with home-based phototherapy using a Waldmann UV100L-TL01 lamp. Clinical effectiveness was determined on the basis of achieving a 75% improvement in Psoriasis Area and Severity Index (PASI 75) within 16 weeks of treatment. RESULTS: Treatment was considered to be effective in 5 out of 6 patients (83%) treated with biologics and 4 out of 6 patients (66%) treated with home-based phototherapy. The direct costs required to achieve PASI 75 were 8256? per patient for biologics and 903? per patient for home-based phototherapy. The costs associated with effective treatment using biologic drugs in a single patient would provide effective home-based phototherapy for 9.1 patients. LIMITATIONS: The study included a limited number of patients analyzed over a short time period (16 weeks) and the comparison group included multiple treatments with different predicted responses. CONCLUSIONS: Although biologic drugs exhibited greater efficacy, home-based phototherapy was more efficient for the treatment of moderate to severe psoriasis. Home-based phototherapy represents a cost-effective treatment option for patients with psoriasis and may be appropriate for use in the Spanish health care system. PMID- 22036023 TI - Postscript on advantame--a novel high-potency low-calorie sweetener. PMID- 22036024 TI - Advantame--an overview of the toxicity data. AB - Advantame is an N-substituted (aspartic acid portion) derivative of aspartame that is similar in structure to neotame, another N-substituted aspartame. An extensive series of studies, were conducted on advantame to define the pharmacokinetics and metabolism in various species, subchronic and chronic toxicity in the rat and dog, carcinogenicity in the rat and mouse, genotoxicity, reproductive, and developmental toxicity, and human tolerability studies. The results of these studies, presented in overview in the present publication, and in greater detail in the accompanying publications, show that advantame is well tolerated by both animals and humans and does not possess systemic toxicity. The metabolic data demonstrate that the animal species used in the toxicity testing are relevant to the evaluation of human safety. The no-observed-adverse-effect levels (NOAELs) identified in the animal studies in which advantame was administered in the diet were generally the highest doses tested. Under the anticipated conditions of use, the predicted intakes of advantame are about 20,000- to 70,000-fold lower than the identified animal study NOAEL values. The results of the animal toxicology and human trial data support the safety of use of advantame in food. PMID- 22036025 TI - In vitro and in vivo assessment of the mutagenic activity of N-[N-[3-(3-hydroxy-4 methoxyphenyl) propyl]-alpha-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame). AB - Advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-alpha-aspartyl]-L phenylalanine 1-methyl ester, monohydrate), an N-substituted analogue of aspartame, has been developed as a high-intensity sweetener. It is approximately 100 and 20,000 times sweeter than aspartame and sucrose, respectively. In this study the safety of advantame has been evaluated using a series of in vitro and in vivo genotoxicity assays including, bacterial mutation, mammalian cell mutation, and mouse micronucleus tests. Advantame did not induce reverse mutations in Salmonella typhimurium and Escherichia coli at concentrations of up to 5000 MUg/plate. In the mammalian cell mutation assay, advantame did not induce mutation at the Hprt locus of L5178Y mouse lymphoma cells in two independent experiments, either in the absence or presence of S9. In vivo, there was no effect on the incidence of micronucleated immature or mature erythrocytes in bone marrow after oral administration of the test substance at any dose level (up to 2000 mg/kg body weight) or sampling time (24 and 48 h). The results of these studies demonstrate that advantame is without genotoxic potential. PMID- 22036026 TI - Chronic toxicity and carcinogenicity of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-alpha-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame) in the rat. AB - Groups of 55 male and 55 female Han Wistar rats were administered advantame (98.9 99.8% purity) in the diet at concentrations of 0, 2000, 10,000, or 50,000 ppm for 104 weeks, following parental exposure to the same levels from prior to mating and throughout gestation. Additional groups of 20 rats/sex and 10 rats/sex were dosed for a period of 52 weeks and constituted the toxicity and reversibility phases of the study. Achieved doses of advantame over the carcinogenicity study were 0, 97, 488, and 2621 mg/kg body weight/day in males and 0, 125, 630, and 3454 mg/kg body weight/day in females, respectively. A high incidence of a pale and swollen anus and changes in fecal composition were observed in the high-dose groups. There was no effect of treatment on mortality. Body weight gain in the high-dose males (50,000 ppm) was slightly reduced compared to controls after 52 and 104 weeks of treatment; the decrease was not considered to be of toxicological significance, but due to the non-nutritive nature of the high dietary concentration of advantame. During the toxicity phase, food conversion efficiency was slightly decreased in both sexes, at the 50,000 ppm dose level. Given the non-nutritive content of the diet, this finding was not considered biologically significant. There were no relationships between treatment and the results of hematological or urinalysis investigations. Clinical chemistry evaluations showed consistently lower plasma urea concentrations in both sexes treated at 50,000 ppm, which was reversed during the 6-week recovery phase following 52 weeks of treatment, indicating a lack of permanent effects. Terminal investigations at both the 52 and 104-week revealed a number of intergroup differences in absolute and/or relative organ weights; however, the differences did not show dose-response relationships, were minor in nature, and/or occurred only in one sex, and were not associated with any pathological findings, and they were considered not to be treatment-related. Evaluation of the histopathology of the carcinogenicity phase animals revealed an increased incidence of pancreatic islet cell carcinomas in males (incidence rates of 0/55, 1/55, 2/55, and 3/55 in the 0, 2000, 10,000, or 50,000 ppm groups, respectively) and of mammary gland adenomas in the high-dose females (incidence rates of 0 in the control through 10,000 ppm dose groups and 4/41 in the 50,000 ppm dose group). The incidence rates of these tumors did not attain statistical significance and/or remained within background historical control values, and they were considered to be unrelated to advantame treatment. The no-observed-adverse-effect level was considered to be 50,000 ppm in the diet, the highest concentration tested, equivalent to 2621 and 3454 mg/kg body weight/day in males and females, respectively. Advantame was concluded to be without carcinogenic activity. PMID- 22036027 TI - Chronic oral toxicity of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-alpha aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame) in the dog. AB - Advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-alpha-aspartyl]-L phenylalanine 1-methyl ester, monohydrate), an N-substituted analog of aspartame, has been developed as a high-intensity sweetener. Groups of 4 dogs of each sex were treated at 0, 2000, 10,000, or 50,000 ppm of advantame in the diet for 52 weeks. Additional groups of 2 dogs/sex at the control, and mid- and high-dose groups were treated for 52 weeks followed by a 6-week recovery period. There was no effect of treatment on mortality, body weight, organ weights, food consumption, or the results of ophthalmological, electrocardiographic, haematological, clinical chemistry or urinalysis examinations. No histopathological changes were associated with advantame treatment. The NOAEL was considered to be 50,000 ppm, the highest concentration tested, which was equivalent to 2057 and 2139 mg/kg body weight/day in males, and females, respectively. The results of the study support the safety of advantame for use as a high-intensity sweetener. PMID- 22036028 TI - Evaluation of the teratogenic potential of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-alpha-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame) in the rat and rabbit. AB - To assess its teratogenic potential, advantame (N-[N-[3-(3-hydroxy-4 methoxyphenyl) propyl]-alpha-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate) was administered to mated rats (22/group) in the diet at 0, 5000, 15,000, and 50,000 ppm (providing approximately 465, 1418, and 4828 mg/kg body weight/day), and to mated rabbits (24/group) via oral gavage at 0, 500, 1000, and 2000 mg/kg body weight/day throughout gestation. Shortly before delivery (rats: day 20; rabbits: day 29), animals were killed and subjected to a detailed necropsy. Fetuses were examined for external, visceral, and skeletal alterations. Atypical coloration of the feces and cage liners seen with test diets in both rats and rabbits was attributed to excretion of test material/metabolites in the feces and urine. Advantame had no adverse effect on rat offspring survival or development. The no-observed-adverse-effect level (NOAEL) for both maternal and developmental toxicity in rats was 50,000 ppm, the highest dietary concentration tested. Due to adverse effects associated with reduced food intake and fecal output, approximately 20% of mated rabbits receiving 200 0mg/kg body weight/day and 1 animal at 1000 mg/kg body weight/day had to be terminated before scheduled necropsy. A NOAEL of 500 mg/kg body weight/day was established for maternal toxicity in rabbits. No teratogenic effects were observed in any animals, and based on a slightly increased incidence of fetal deaths at 2000 mg/kg body weight/day, a finding that was considered to be indirectly related to advantame treatment, 1000 mg/kg body weight/day was considered the NOAEL for developmental toxicity. PMID- 22036029 TI - Acute and multiple-dose studies to determine the safety, tolerability, and pharmacokinetic profile of advantame in healthy volunteers. AB - Advantame, a new, high-intensity sweetener that is thought not to be absorbed from the human gastrointestinal tract in appreciable quantities, was evaluated for safety and tolerability in a total of 48 healthy adult volunteers in 2 studies. In the first study 24 subjects were randomized to receive escalating single doses of 0.1, 0.25, or 0.5mg/kg of body weight, and pharmacokinetic and safety parameters were assessed subsequently for 8 days. In the second study, 24 subjects were randomized to receive over 4 weeks either 30 mg advantame/day (split into 3 doses per day), or placebo. All subjects completed both studies and no significant treatment-related adverse effects were observed in any subjects in either study. There were no clinically relevant changes in laboratory parameters, vital signs, electrocardiogram, or physical examination findings. Plasma concentrations of advantame were mostly below the limit of quantification in all samples taken after a single dose or prior to the dose in the repeat-dose study. The concentrations of the hydrolysis product, advantame-acid, were also below the limit of quantification at 12, 36, and 48 h after a single dose of 0.1, 0.25, and 0.5mg/kg body weight, respectively. These studies demonstrate the safety and tolerability of advantame in healthy subjects at doses far exceeding those likely to be encountered in food and beverage use. PMID- 22036030 TI - Pharmacokinetics and metabolism of N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl] alpha-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate (advantame) in the rat, dog, and man. AB - The pharmacokinetics and metabolism of advantame were evaluated in rats, dogs, and humans. The oral pharmacokinetic studies using (14)C-advantame showed that advantame undergoes rapid but incomplete absorption, with an oral bioavailability of total radioactivity in the range of 4-23%. Data indicated that absorption was mainly as ANS9801-acid (de-esterified advantame), which was formed in the gastrointestinal tract as a result of the hydrolysis of the methyl ester group of the parent compound. In the dog, plasma ANS9801-acid was present largely in the form of an unidentified conjugate. Advantame (chiefly in the form of metabolites) was mainly excreted in the feces in rats, dogs, and humans (>80% in each species), with urinary excretion representing a minor route. The predominant metabolite of (14)C-advantame detected in the feces and the urine of rats, dogs, and humans was ANS9801-acid, with lower amounts of 3-[3-hydroxy-4-methoxyphenyl] 1-propylamine (termed HU-1) or N-(3-(3-hydroxy-4-methoxy phenyl))propyl-L aspartic acid (termed HF-1) present, as well as other minor metabolites and areas of indistinct radioactivity. ANS9801-acid, HU-1, and HF-1 were detected and identified in the urine of rats, humans, and dogs, while ANS9801-acid and HF-1 were identified in the feces of humans and dogs. In the feces of rats, in addition to ANS9801-acid, other additional metabolites were detected, including demethylated ANS9801-acid (designated as RF-1) and another unidentified metabolite (designated as RF-2). Overall, the data show generally similar pharmacokinetics of advantame and ANS9801-acid in animals and in humans and close similarity with neotame. Metabolites of advantame that occur in humans are also found in the 2 species utilized in the toxicology studies, and the metabolism studies support the interpretation of safety data from studies conducted in rats and dogs. PMID- 22036031 TI - Re: Andrade NN, Raikwar K. Congenital benign teratoma of the tongue with bifid tip, ankyloglossia and polydactyly: report of case. PMID- 22036032 TI - Multiscale modeling of lymphatic drainage from tissues using homogenization theory. AB - Lymphatic capillary drainage of interstitial fluid under both steady-state and inflammatory conditions is important for tissue fluid balance, cancer metastasis, and immunity. Lymphatic drainage function is critically coupled to the fluid mechanical properties of the interstitium, yet this coupling is poorly understood. Here we sought to effectively model the lymphatic-interstitial fluid coupling and ask why the lymphatic capillary network often appears with roughly a hexagonal architecture. We use homogenization method, which allows tissue-scale lymph flow to be integrated with the microstructural details of the lymphatic capillaries, thus gaining insight into the functionality of lymphatic anatomy. We first describe flow in lymphatic capillaries using the Navier-Stokes equations and flow through the interstitium using Darcy's law. We then use multiscale homogenization to derive macroscale equations describing lymphatic drainage, with the mouse tail skin as a basis. We find that the limiting resistance for fluid drainage is that from the interstitium into the capillaries rather than within the capillaries. We also find that between hexagonal, square, and parallel tube configurations of lymphatic capillary networks, the hexagonal structure is the most efficient architecture for coupled interstitial and capillary fluid transport; that is, it clears the most interstitial fluid for a given network density and baseline interstitial fluid pressure. Thus, using homogenization theory, one can assess how vessel microstructure influences the macroscale fluid drainage by the lymphatics and demonstrate why the hexagonal network of dermal lymphatic capillaries is optimal for interstitial tissue fluid clearance. PMID- 22036033 TI - Design and experimental evaluation of adjustable bone plates for mandibular fracture fixation. AB - Conventional bone plates are commonly used for surgical mandibular fracture fixation. Improper alignment between bone segments, however, can result in malocclusion. Current methods of fixation require a surgeon to visually align segments of bone and affix a metal plate using bone screws, after which little can be done to adjust alignment. A method of adjusting fracture alignment after plate placement, without screw removal, presents an improvement over costly and risky revision surgery. A modified bone plate has been designed with a deformable section to give surgeons the ability to reduce misalignments at the fracture site. The mechanics of deformation for various adjustment mechanisms was explored analytically, numerically, and experimentally to ensure that the adjustable plate is comparable to conventional bone plates. A static force of 358.8 N is required to deform the adjustable bone plate, compared with predicted values of 351 N using numerical simulation and 362 N using a simple beam theory. Dynamic testing was performed to simulate in vivo loading conditions and evaluate load-capacity in both deformed and un-deformed bone plates. Results indicate that bending stiffness of a rectangular bone plate is 709 N/mm, compared with 174 N/mm for an octagonal plate and 176 N/mm for standard plates. Once deformed, the rectangular and octagonal plates had a stiffness of 323 N/mm and 228 N/mm, respectively. Un deformed and deformed adjustable bone plates have efficacy in bone segment fixation and healing. PMID- 22036034 TI - Evidence for impaired neocortical synaptic plasticity in bipolar II disorder. AB - BACKGROUND: Synaptic plasticity might play an important role in the pathophysiology and treatment of bipolar disorders. There is, however, a paucity of human evidence supporting this hypothesis, mainly due to a lack of methods for noninvasive assessment of synaptic plasticity. It has recently been demonstrated that plasticity of the visual evoked potential (VEP) induced by repeated visual stimulation might reflect synaptic plasticity. In this study, we examined VEP plasticity in healthy control subjects and patients with bipolar II disorder (BD II). METHODS: Forty healthy control subjects and 26 individuals with a DSM-IV diagnosis of BD-II matched for age and gender participated. The VEPs were evoked by checkerboard reversal stimulation before and after a modulation block of prolonged (10 min) visual stimulation. RESULTS: The modulation block resulted in significant VEP plasticity in healthy control subjects. The VEP plasticity was significantly impaired in patients with BD-II. Explorative analyses indicated a trend toward a less severe impairment in medicated than in unmedicated patients. CONCLUSIONS: Visual evoked potential plasticity might represent a reliable and robust assay for studies of synaptic plasticity in vivo in humans. In addition, our findings support the hypothesis of impaired synaptic plasticity in BD-II. Longitudinal studies are needed to fully clarify the effects of medication and mood state on VEP plasticity. PMID- 22036035 TI - Attention and masking in schizophrenia. AB - BACKGROUND: Patients with schizophrenia are known to be impaired in masking tasks, but the mechanisms underlying their deficits are still elusive. Our study was intended to examine attentional effects, which have a known impact on masking in healthy volunteers but have only rarely been explored in relation to masking in patients. METHODS: We compared focused versus divided attention in 18 control subjects and 18 patients using forward and backward masking tasks. In the conventional masking task, subjects had to locate one target among four possible locations. Presentation of one target allows attention to be focused, in contrast with the divided attention task in which two targets were presented either in the same hemifield or different hemifields. RESULTS: Our results reproduce patients' deficits in forward and backward masking tasks but only when one target is presented. We show that control subjects benefit from focused attention, much more so than patients. Furthermore, patients' performance is identical to that of control subjects in backward masking when targets are presented across hemifields. This performance equalization was checked to ensure it was not due solely to the redundancy of signals (two vs. one). We achieved this by comparing performance when two targets were presented in the same vs. across hemifields, the latter yielding a greater redundancy gain. CONCLUSIONS: From the results, it is unlikely that redundancy can account for the whole pattern of results, which suggest instead that attention deficits play a role in backward masking impairments in patients. PMID- 22036037 TI - Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: implications for schizophrenia. AB - BACKGROUND: Levels of cannabinoid 1 receptor (CB1R) messenger RNA (mRNA) and protein, which are expressed most heavily in the cholecystokinin class of gamma aminobutyric acid (GABA) neurons, are lower in the dorsolateral prefrontal cortex in schizophrenia, and the magnitude of these differences is strongly correlated with that for glutamic acid decarboxylase 67 (GAD(67)) mRNA, a synthesizing enzyme for GABA. However, whether this correlation reflects a cause-effect relationship is unknown. METHODS: Using quantitative in situ hybridization, we measured CB1R, GAD(67), and diacylglycerol lipase alpha (the synthesizing enzyme for the endocannabinoid 2-arachidonoylglycerol) mRNA levels in the medial prefrontal cortex of genetically engineered GAD(67) heterozygous (GAD(67)(+/-)), CB1R heterozygous (CB1R(+/-)), CB1R knockout (CB1R(-/-)), and matched wild-type mice. RESULTS: In GAD(67)(+/-) mice, GAD(67) and CB1R mRNA levels were significantly reduced by 37% and 16%, respectively, relative to wild-type mice and were significantly correlated across animals (r = .61; p = .01). In contrast, GAD(67) mRNA levels were unaltered in CB1R(+/-) andCB1R(-/-) mice. Expression of diacylglycerol lipase alpha mRNA, which is not altered in schizophrenia, was also not altered in any of the genetically engineered mice. CONCLUSIONS: The findings that reduced GAD(67) mRNA expression can induce lower CB1R mRNA expression support the hypothesis that lower cortical levels of CB1Rs in schizophrenia may partially compensate for deficient GAD(67)-mediated GABA synthesis by reducing endogenous cannabinoid suppression of GABA release. PMID- 22036036 TI - Glutamatergic modulation of auditory information processing in the human brain. AB - BACKGROUND: Auditory mismatch negativity (MMN) and P300 event-related potentials (ERPs) are reduced in schizophrenia patients and healthy volunteers administered the N-methyl-D-aspartate glutamate receptor antagonist, ketamine. In rodents, N acetylcysteine (NAC), a stimulator of the cystine-glutamate exchanger, attenuates the cognitive and behavioral effects of N-methyl-D-aspartate receptor antagonists. On the basis of these findings, we tested whether NAC would reduce ketamine effects on behavior, MMN, and P300 in healthy humans. METHODS: This randomized, double-blind, placebo-controlled study consisted of 2 test days during which subjects (n = 16) were administered oral NAC (3000 mg in divided doses) or matching placebo 165 min before the infusion of saline and then ketamine (as a bolus of .23 mg/kg over 1 min followed by .58 mg/kg for 30 min, and then .29 mg/kg for 40 min) in a fixed order. Behavioral and ERP data including auditory MMN and P300 were collected during each test day. RESULTS: Ketamine produced psychotic-like positive symptoms, reductions in working memory and sustained attention performance, and amplitude reductions for the frequency- and intensity-deviant MMNs and P300. NAC pretreatment did not reduce the behavioral or ERP effects of ketamine. In addition, NAC reduced frequency-deviant MMN amplitude and increased target and novelty P3 amplitudes. The decrements in frequency-deviant MMN amplitude produced by ketamine and NAC were not additive. CONCLUSIONS: NAC did not attenuate the effects of ketamine in humans, in contrast to previous studies in animals. NAC merits further investigation as a cognitive enhancing agent due to its ability to increase the P300 amplitude. PMID- 22036039 TI - Molecular and antigenic evolution of human influenza A/H3N2 viruses in Quebec, Canada, 2009-2011. AB - BACKGROUND: A/H3N2 variability leads to poor vaccine effectiveness when the vaccine strain is not well matched to the circulating virus. OBJECTIVES: We aim to describe the molecular and antigenic evolution of A/H3N2 viruses recovered during the last 3 influenza seasons in Quebec, Canada. STUDY DESIGN: Clinical samples from 33 patients with culture-confirmed A/H3N2 infections were collected over 3 consecutive seasons (March 2009-2011). The isolates' HA gene was amplified and sequenced; phylogenetic analyses of the HA1 region were conducted. To characterize A/H3N2 antigenic properties, standard hemagglutination inhibition (HI) and microneutralization (MN) assays were performed. RESULTS: In 2009, we observed an antigenic drift from A/Brisbane/10/2007 (vaccine strain used in 2008 2009 and 2009-2010) to A/Perth/16/2009 (vaccine strain used in 2010-2011). Antigenic analysis of clinical influenza strains recovered in Quebec during 2009 2010 also illustrated antigenic drift from the previously prevalent A/Brisbane/10/2007-like (March 2009) to A/Perth/16/2009-like (December 2009) strains. In 2010-2011, the emergence of >4 substitutions in 4 different H3 antigenic sites suggested a genetic drift. However, HI and MN results confirmed the emergence of a drift in only 1 strain (8-fold difference in titers), while 19 others remained antigenically similar to A/Perth/16/2009 but exhibited titer differences (2-4-fold) just inferior to the standard definition of a drift. CONCLUSION: Antigenic and molecular characterization of H3N2 viruses over three seasons revealed that not only is the number of HA mutations important, but the nature and location of key mutations may play a significant role in antigenic drift. PMID- 22036038 TI - Brain-derived neurotrophic factor Val66Met allele impairs basal and ketamine stimulated synaptogenesis in prefrontal cortex. AB - BACKGROUND: Knock-in mice with the common human brain-derived neurotrophic factor (BDNF) Val66Met polymorphism have impaired trafficking of BDNF messenger RNA to dendrites. It was hypothesized, given evidence that local synapse formation is dependent on dendritic translation of BDNF messenger RNA, that loss-of-function Met allele mice would show synaptic deficits both at baseline and in response to ketamine, an N-methyl-D-aspartate antagonist that stimulates synaptogenesis in prefrontal cortex (PFC). METHODS: Whole-cell recordings from layer V medial PFC pyramidal cells in brain slices were combined with two-photon laser scanning for analysis of wildtype, Val/Met, and Met/Met mice both at baseline and in response to a low dose of ketamine. RESULTS: Val/Met and Met/Met mice were found to have constitutive atrophy of distal apical dendrites and decrements in apically targeted excitatory postsynaptic currents in layer V pyramidal cells of PFC. In addition, spine density and diameter were decreased, indicative of impaired synaptic formation/maturation (synaptogenesis). In Met/Met mice the synaptogenic effect of ketamine was markedly impaired, consistent with the idea that synaptogenesis is dependent on dendritic translation/release of BDNF. In parallel behavioral studies, we found that the antidepressant response to ketamine in the forced swim test was blocked in Met/Met mice. CONCLUSIONS: The results demonstrate that expression of the BDNF Met allele in mice results in basal synaptic deficits and blocks synaptogenic and antidepressant actions of ketamine in PFC, suggesting that the therapeutic response to this drug might be attenuated or blocked in depressed patients who carry the loss of function Met allele. PMID- 22036040 TI - Emergent 2009 influenza A(H1N1) viruses containing HA D222N mutation associated with severe clinical outcomes in the Americas. AB - BACKGROUND: During the 2010-2011 influenza season, a small sub-group of 2009 influenza A(H1N1) viruses (hereafter referred to as 2009 A(H1N1)) emerged that was associated with more severe clinical outcomes in Ecuador and North America. Genetically, the haemagglutinin (HA) of this sub-clade was distinct from HAs found in viruses associated with severe outbreaks in 2010 from the United Kingdom and from other global specimens isolated earlier in the season. OBJECTIVE: We report the emergence of a novel 2009 A(H1N1) variant possessing a re-emergent HA D222N mutation obtained from patients with severe respiratory illnesses and phylogenetically characterise these D222N mutants with other severe disease causing variants clustering within a common emerging sub-clade. CASE REPORTS: In early 2011, three cases of 2009 A(H1N1) infection, two from Quito, Ecuador, and one from Washington, DC, USA, were complicated by severe pneumonia requiring mechanical ventilation, resulting in one fatality. These cases were selected due to the reported nature of the acute respiratory distress (ARD) that were captured in Department of Defence (DoD)-sponsored global influenza surveillance nets. RESULTS: Genetically, the 2009 A(H1N1) strains isolated from two of the three severe cases carried a prominent amino acid change at position 222 (D222N) within the primary HA receptor binding site. Furthermore, these cases represent an emerging sub-clade of viruses defined by amino acid changes within HA: N31D, S162N, A186T and V272I. Phylogenetically, these viruses share a high degree of homology with strains associated with recent fatal cases in Chihuahua, Mexico. DISCUSSION: Previously, enhanced virulence associated with the change, D222G, has been clinically linked to severe morbidity and mortality. Initial observations of the prevalence of a novel sub-clade of strains in the Americas suggest that viruses with a re-emergent D222N mutation may too correlate with severe clinical manifestations. These findings warrant heightened vigilance for emerging sub clades of 2009 A(H1N1) and presumptive clinical implications. PMID- 22036041 TI - Evolution in the sensitivity of quantitative HIV-1 viral load tests. AB - Significant advancements in molecular diagnostics have been made since the inception and application of PCR-based technologies in clinical diagnostic laboratories and the management of HIV-1 infected patients. More recently, real time PCR has improved the overall performance of assays used for detecting and quantifying HIV-1 RNA viral load in patients undergoing antiretroviral treatment. The effects of these changes and the interpretations of the HIV-1 viral load results are discussed in this review in the context of the different assays used, the viral dynamics of the HIV-1 virus, and the recent changes to HIV-1 treatment guidelines. PMID- 22036042 TI - A need to expand our thinking about "repeat" abortions. AB - BACKGROUND: Women who have more than one abortion are often the "targets" for social and clinical interventions geared at preventing "repeat abortions." Such an approach ignores the unique circumstances that may surround each abortion. STUDY DESIGN: We qualitatively analyzed the history of 10 women who have had more than one abortion who were participating in a larger study of women's emotional experiences following abortion. Women were recruited following their initial contact with a postabortion support talk line and from a previously completed study. RESULTS: Overall, women in the sample reported that each abortion was different and some abortions were more emotionally difficult than others, suggesting that the phrase "repeat" can be a misnomer and discounts the unique circumstances surrounding each abortion. CONCLUSION: Rather than use the term "repeat abortions," we advocate for the use of the less loaded term "multiple abortions," in which each abortion is understood as a unique experience. PMID- 22036043 TI - Management of the malpositioned levonorgestrel-releasing intrauterine system. AB - BACKGROUND: The management of a malpositioned levonorgestrel (LNG)-releasing intrauterine system (IUS) can present a clinical challenge, complicated by the high cost of replacing it with a new device. We tried to challenge the guidelines and common practice that usually suggest prompt removal of any malpositioned IUS and replacement with a new one. STUDY DESIGN: We present our experience with 18 patients in whom the LNG-releasing IUS was found during a routine sonographic evaluation to be displaced towards the cervical canal 2 to 36 months postinsertion. Using an alligator forceps, the device was repositioned in the uterine cavity. RESULTS: The procedure was deemed successful in 17 (94.4%) of 18 cases. In 3 (17.6%) of the 17 successful procedures, the LNG-releasing IUS was found again to be malpositioned within 2 months. No complications were noted, and no postprocedural infection occurred. CONCLUSION: Repositioning of a malpositioned LNG-releasing IUS should be considered, as it is an easy and simple manipulation that can be done in the office with a high success rate and minimal risk of complications. PMID- 22036045 TI - Clinical outcomes from a prospective study evaluating the role of ambulation during medical termination of pregnancy. AB - BACKGROUND: Although induced abortion is one of the most commonly performed gynecological procedures in Great Britain and medical termination of pregnancy is being used more frequently, very little is known about the role of ambulation during the procedure. We sought to compare ambulatory and non-ambulatory groups of patients undergoing medical termination in the hospital setting and determine whether ambulation impacted clinical outcomes. STUDY DESIGN: This was a prospective patient-preference study carried out among 130 women with pregnancies up to 63 days of gestation fulfilling the requirements of the 1967 Abortion Act and undergoing medical termination of pregnancy. The objective was to evaluate the effect of ambulation during medical termination of pregnancy. The women were given the choice to be ambulatory or non-ambulatory throughout the process of medical termination of pregnancy. They received 200 mg oral mifepristone and 800 mcg vaginal misoprostol for the termination procedure. Outcomes measured included time taken to pass the products of conception, first feeling of abdominal cramps, estimated blood loss, time to discharge from the hospital, pain scores and need for analgesia. RESULTS: In both ambulatory and non-ambulatory groups, the mean time taken to pass the products of conception was similar: 230.7 min (118-343.4) and 233.0 min (134.5-331.5) for ambulatory and non-ambulatory patients, respectively. Time to onset of cramps was 75.6 min (29.4-121.8) for ambulatory and 91.7 min (22.2-161.2) for non-ambulatory patients, from administration of misoprostol. Mean estimated blood loss (assessed by weighing the pads as well as blood in bed pan) was less than 100 mL in both groups, and overall, approximately 85% of patients ranked their pain score as 3 or less (on a scale of 0-5). There were no statistically significant differences in the ambulatory versus non ambulatory groups with regard to clinical outcomes. CONCLUSION: Ambulation during medical termination of pregnancy neither appears to influence the amount of bleeding or pain nor hasten the process of medical termination of pregnancy. PMID- 22036044 TI - Tubal risk markers for failure to place transcervical sterilization coils. AB - BACKGROUND: There is a growing body of literature on placement rates of the Essure(r) procedure, yet prior studies have not attempted to identify tubal associated risk factors for placement failures. The current study examines risk markers associated with the inability to deploy the Essure(r) coils into the tubal lumen using the new ESS305 design. STUDY DESIGN: We used electronic medical record data to assess risk markers associated with the inability to place the Essure coils in the tubal lumen using the new ESS305 design. A total of 310 attempted procedures between June 14, 2007, and April 29, 2011, were analyzed. RESULTS: There were 18 tubal failures (5.8%) out of the 310 attempted procedures. A history of a prior sexually transmitted infection (STI) was associated with tubal failure (odds ratio 2.64, 95% confidence interval 1.01-6.90, p=.048). CONCLUSIONS: We speculate that the observed association between a prior STI and an inability to place the coil was due to a past history of pelvic inflammatory disease. PMID- 22036046 TI - Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. AB - Contraception for HIV-positive women is a complex issue. Although the use of condoms is recommended, complementary methods of contraception are often prescribed. Antiretroviral therapy can lead to drug interactions and modify the efficacy of hormonal contraception. Two unintended pregnancies suggest that etonogestrel implants should be used with caution in patients on efavirenz. PMID- 22036047 TI - Poor responders: still a problem. PMID- 22036048 TI - A systematic review of randomized trials for the treatment of poor ovarian responders: is there any light at the end of the tunnel? AB - OBJECTIVE: To assess the definitions for "poor ovarian responders" used among randomized trials for the treatment of women with impaired response to stimulation. DESIGN: Systematic review. SETTING: None. PATIENT(S): Poor ovarian responders. INTERVENTION(S): Treatment modalities for the management of poor ovarian responders. MAIN OUTCOME MEASURE(S): Number and nature of the criteria used to define poor ovarian response to stimulation and threshold values used. RESULT(S): Among 47 randomized trials, 41 different definitions for the patients with poor ovarian response have been used. No more than 3 trials used the same definition, whereas even trials from the same research groups used different definitions across different trials. None of the criteria used was adopted in more than 50% of the trials. Age and antral follicle count were adopted only in 9% of the definitions, whereas the criteria of number of follicles on the final stimulation day and number of oocytes retrieved were used in more than 40% of the trials; nonetheless, even for these criteria, the threshold values were consistently different. CONCLUSION(S): The variability regarding the definition of poor ovarian responders appears to be striking. Although the Bologna criteria developed by European Society for Human Reproduction and Embryology consensus in 2011 aim to define a consistent group of patients, their applicability needs to be tested through clinical trials. Meanwhile, meta-analyses of the currently available trials should be strongly discouraged because they may lead to the adoption of interventions of ambiguous value. PMID- 22036049 TI - Androgens and poor responders: are we ready to take the plunge into clinical therapy? AB - OBJECTIVE: To review and summarize data from the scientific literature on the use of androgens to improve ovarian function. DESIGN: Review of pertinent literature. SETTING: University hospital. PATIENT(S): Women exposed to androgens. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Critical review of the literature. RESULT(S): The artificial increase of intra-ovarian androgen concentrations constitutes an attractive concept for improving the deficient ovarian function of poor responders. Data from studies conducted in animals treated with high-dose androgens, together with observations made in hyperandrogenic women or female-to-male transsexuals receiving virilizing androgen doses, indicate that androgens may increase follicle responsiveness to FSH and/or the number of growing follicles in the ovary. Yet, definite clinical demonstration of such a concept still is not available. CONCLUSION(S): Current clinical approaches aiming at increasing androgen availability in the ovary showed conflicting results. Therefore, additional studies using proper strategies to achieving higher intra-ovarian androgen concentrations for longer intervals are required to define the clinical efficiency of androgens in poor responders. PMID- 22036050 TI - Modified natural-cycle in vitro fertilization should be considered as the first approach in young poor responders. AB - The use of modified natural-cycle in vitro fertilization (IVF) is a valuable alternative to controlled ovarian hyperstimulation in young poor responders and should be considered in patients who require IVF and demonstrate endocrinologic evidence of ovarian aging and in those who have had one or two canceled controlled ovarian hyperstimulation cycles. PMID- 22036051 TI - The value of growth hormone supplements in ART for poor ovarian responders. AB - Recently, three meta-analyses have concluded that cotreatment with GH improves assisted reproduction outcome in poor controlled ovarian stimulation responders. Although generally GH supplements did not increase controlled ovarian stimulation response or number of oocytes, the supplements improved pregnancy and live-birth rates-thus speaking for an effect on oocyte quality. PMID- 22036052 TI - mTOR kinase inhibition results in oocyte loss characterized by empty follicles in human ovarian cortical strips cultured in vitro. AB - OBJECTIVE: To determine whether oocyte loss is induced by mTOR kinase inhibition in human cortical strips as seen in model organisms in vivo and in vitro. DESIGN: Ovarian cortex was collected at two centers and cut into small strips. Strips were cultured for 6 days with or without the mTOR inhibitor rapamycin (RAP; 100 nM). Strips were then embedded in paraffin, and serial sections were prepared. SETTING: Samples were collected in general obstetric (Edinburgh), gynecologic surgery (New Haven), and fertility preservation assisted reproductive technology (ART) (New Haven) practices. PATIENT(S): Ovarian cortex collected from patients (15-34 years of age) during cesarean section (donated tissue) was removed for the purposes of fertility preservation or was prepared after oophorectomy. INTERVENTION(S): Tissue was used for research purposes only, with no subsequent patient intervention. MAIN OUTCOME MEASURE(S): Follicles were counted and assessed in each serial section. Caspase activity was monitored to determine whether mTOR inhibition activated apoptosis. RESULT(S): The RAP inclusion in cultures results in significantly fewer follicles compared with ethanol vehicle treated controls. Furthermore, RAP treatment resulted in the induction of follicles that lacked an oocyte in any serial section (30/161 follicles vs. 1/347 ethanol vehicle-treated follicles). Caspase activity was not elevated by RAP treatment. CONCLUSION(S): mTOR inhibition results in a conserved destruction of the oocyte by adjacent granulosa cells (GC) in the absence of increased caspase activity. This model of oocyte loss is not consistent with classic apoptosis/atresia. PMID- 22036055 TI - Using the Drinking Expectancy Questionnaire (revised scoring method) in clinical practice. AB - The Drinking Expectancy Questionnaire (Young & Knight, 1989; Young & Oei, 1996) has been widely used in clinical and research settings over the past 20 years. A revised scoring method with a five-factor structure has been proposed but no norms for this method are available (Lee, Oei, Greeley, & Baglioni, 2003). The aim of this study is to establish sample means for the five expectancy subscales (Social Confidence; Sexual Interest; Cognitive Enhancement; Tension Reduction; and Negative Consequences) in a sample of adults entering hospital treatment for alcohol dependence (N=163) and a sample of university undergraduate students (N=110). Clinical sample means on the expectancy subscales tended to be substantially higher than the means for the student sample, with the exception of Sexual Interest (which was higher in the students). Interestingly, the Negative Consequences subscale mean was more than two standard deviations higher in the clinical sample, and was strongly correlated with measures of depression, anxiety and stress. The Negative Consequences scores were strongly associated with drinking risk in the student sample but were not related to drinking measures in the clinical sample. A ROC analysis established a cut-off on the DEQ total of 107 that distinguished dependent drinkers from student drinkers with high sensitivity and specificity. The clinical utility of the DEQ in general will be discussed. PMID- 22036054 TI - Therapy-related acute leukemia with mixed phenotype and t(9;22)(q32;q11.2): a case report and review of the literature. AB - Therapy-related acute leukemia showing mixed phenotype is extremely rare. We report a 49-year-old woman who presented with palpable masses in her neck and back. She had received systemic chemotherapy (adriamycin and cisplatin) and radiotherapy for endometrial adenocarcinoma 7 years before. Her peripheral blood and bone marrow showed increased blasts, which coexpressed myeloid (CD13, CD33, and myeloperoxidase) and B-lymphoid antigens (CD19 and CD79a). Cytogenetic analysis showed a karyotype of 46,XX,dup(1)(q21q32),add(5)(q33),t(9;22)(q34;q11.2)[12]/47,idem,+der(22)t(9;22)[8 , and BCR/ABL1 rearrangement was detected. Leukemic infiltration was also confirmed in her back mass. After induction chemotherapy with idarubicin, cytarabine, and imatinib, she achieved complete remission. Only 2 cases of therapy-related acute leukemia with mixed phenotype have been reported so far: one with hyperploidy and the other with t(1;21)(p36;q22). To the best of our knowledge, this is the first case of therapy-related acute leukemia with mixed phenotype and t(9;22) as well as extramedullary leukemic infiltrations. PMID- 22036056 TI - Peering through the smoke: the effect of parental smoking behavior and addiction on daily smokers' attentional bias to smoking cues. AB - Although previous research has demonstrated that individuals with parents who smoke are more likely to become smokers and are less successful in smoking cessation efforts compared with those without a smoking parent, the reasons for this link have not been established. In the current study, implicit attentional bias to smoking-related cues was investigated in college-age smokers, based on models of addiction that suggest that attention to drug-related cues plays an important role in drug addiction. Sixty-one participants completed a dot-probe task to measure attentional bias to smoking-related and matched non-smoking related control pictures. Results indicated that while those who reported smoking occasionally did not demonstrate an attentional bias, daily smokers who had a smoking parent showed more of an attentional bias to the smoking cues than those without a smoking parent, but only to cues that did not contain human content. In addition to parental influence, nicotine dependence explained a significant portion of the variance in the attentional bias for daily smokers. Implications for models of nicotine addiction and the development of smoking cessation programs are discussed. PMID- 22036053 TI - Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease is a global health dilemma. The gold standard for diagnosis is liver biopsy. Ballooned hepatocytes are histologic manifestations of hepatocellular injury and are characteristic of steatohepatitis, the more severe form of nonalcoholic fatty liver disease. Definitive histologic identification of ballooned hepatocytes on routine stains, however, can be difficult. Immunohistochemical evidence for loss of the normal hepatocytic keratin 8/18 can serve as an objective marker of ballooned hepatocytes. We sought to explore the utility of a keratin 8/18 plus ubiquitin double immunohistochemical stain for the histologic evaluation of adult nonalcoholic fatty liver disease. Double immunohistochemical staining for keratin 8/18 and ubiquitin was analyzed using 40 adult human nonalcoholic fatty liver disease core liver biopsies. Ballooned hepatocytes lack keratin 8/18 staining as previously shown by others, but normal-size hepatocytes with keratin loss are approximately 5 times greater in number than keratin-negative ballooned hepatocytes. Keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin deposits show a zonal distribution, are positively associated with each other, and are frequently found adjacent to or intermixed with fibrous matrix. All 3 lesions correlate with fibrosis stage and the hematoxylin and eosin diagnosis of steatohepatitis (all P < .05). Compared with hematoxylin and eosin staining, immunohistochemical staining improves the receiver operating characteristics curve for advanced fibrosis (0.77 versus 0.83, 0.89, and 0.89 for keratin-negative ballooned hepatocytes, normal-size hepatocytes with keratin loss, and ubiquitin, respectively) because immunohistochemistry is more sensitive and specific for fibrogenic hepatocellular injury than hematoxylin and eosin staining. Keratin 8/18 plus ubiquitin double immunohistochemical stain improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Thus, it may help differentiate nonalcoholic steatohepatitis from nonalcoholic fatty liver. PMID- 22036057 TI - Expected to deliver: alignment of regulation, training, and actual performance of emergency obstetric care providers in Malawi and Tanzania. AB - OBJECTIVE: Policy, regulation, training, and support for cadres adopting tasks and roles outside their historical domain have lagged behind the practical shift in service-delivery on the ground. The Health Systems Strengthening for Equity (HSSE) project sought to assess the alignment between national policy and regulation, preservice training, district level expectations, and clinical practice of cadres providing some or all components of emergency obstetric care (EmOC) in Malawi and Tanzania. METHODS: A mixed methods approach was used, including key informant interviews, a survey of District Health Management Teams, and a survey of health providers employed at a representative sample of health facilities. RESULTS: A lack of alignment between national policy and regulation, training, and clinical practice was observed in both countries, particularly for cadres with less preservice training; a closer alignment was found between district level expectations and reported clinical practice. There is ineffective use of cadres that are trained and authorized to provide EmOC, but who are not delivering care, especially assisted vaginal delivery. CONCLUSION: Better alignment between policy and practice, and support and training, and more efficient utilization of clinical staff are needed to achieve the quality health care for which the Malawian and Tanzanian health ministries and governments are accountable. PMID- 22036058 TI - Regional variation in histopathology-specific incidence of invasive cervical cancer among Peruvian women. AB - OBJECTIVE: To evaluate patterns of cervical cancer incidence in Peru by examining variation in 2 common histopathologic types, squamous cell carcinoma (SCC) and adenocarcinoma (ADC), and analyzing trends over time. METHODS: Data on the incidence of invasive cervical cancer between 1984 and 2006 were obtained from 3 population-based cancer registries in Peru: Lima, Trujillo, and Arequipa. For each registry, data quality assessment was performed, crude and age-specific incidence was calculated, and time trends were analyzed. RESULTS: Overall and SCC incidence varied across registries but incidence of ADC did not. Overall and SCC incidence showed significant declines in Trujillo (P<0.05) and modest declines in Lima (P>0.05) over time. ADC incidence showed marginally significant increases among women aged 15-29 years in Trujillo (P=0.10) and modest increases among young women in Lima (P>0.05). CONCLUSION: Population-based cancer registries were an efficient source of data for evaluating the incidence of cervical cancer once data quality had been established. Geographic and temporal variations in cervical cancer burden were documented in Peru. The trends suggest that cervical ADC is increasing among young women in urban Peru, particularly in Trujillo. We recommend supplementing current Papanicolaou test screening with complementary methods of cervical cancer control, including human papillomavirus (HPV) vaccination and HPV DNA testing. PMID- 22036059 TI - Effect of coadministration of dexamethasone with intrathecal morphine on postoperative outcomes after cesarean delivery. AB - OBJECTIVE: To investigate the effect of intrathecal dexamethasone administered with intrathecal morphine at cesarean delivery on postoperative adverse effects and patient satisfaction. METHODS: A triple-blind, randomized, placebo-controlled trial conducted between February 2008 and December 2009 of 120 pregnant women scheduled to undergo cesarean delivery. The patients were randomized into 2 groups: group 1 received 0.2mg of intrathecal morphine plus 8 mg of intrathecal dexamethasone, while group 2 received 0.2mg of intrathecal morphine plus 0.9% saline solution (placebo). The occurrence of postoperative nausea and vomiting (PONV), postoperative itching, number of vomiting attacks, and need for antiemetics were recorded in both groups. Overall patient satisfaction was also recorded. RESULTS: PONV was 3 times less likely to occur in the dexamethasone group than in the placebo group. When vomiting did occur, the number of attacks was lower in the dexamethasone group (23 vs 87 attacks; OR 0.26, 95% CI, 0.18 0.39). Administration of antiemetics was markedly lower in the dexamethasone group (18 vs 49 shots; OR 0.10, 95% CI, 0.04-0.23) and less postoperative itching was experienced (OR 0.39; 95% CI, 0.19-0.81). The dexamethasone group reported significantly higher mean overall satisfaction scores (77 +/- 17 vs 51 +/- 22; mean difference 26.00; 95% CI, 18.97-33.03). CONCLUSION: Intrathecal administration of dexamethasone with morphine significantly decreased PONV and improved overall patient satisfaction after cesarean delivery. PMID- 22036060 TI - Schistosoma mansoni infection among prenatal attendees at a secondary-care hospital in central Sudan. AB - OBJECTIVE: To investigate the epidemiology of Schistosoma mansoni infection among pregnant women in a secondary-care hospital in Geizera state, Sudan. METHOD: Between August and September 2010, a cross-sectional study was conducted and questionnaires were administered to obtain basic sociodemographic and obstetric characteristics of pregnant women attending prenatal care at Araba Waeshreen Hospital. Stool samples were investigated for helminth infection via formol-ether concentration and Kato-Katz techniques. RESULTS: Of 292 pregnant women, 38 (13.0%) had S. mansoni infections. Hymenolepis nana and hookworm infections were present in 5 (1.7%) and 1 (0.3%) women, respectively. The intensity of the S. mansoni infection was light, moderate, and high in 13 (34.2%), 21 (55.3%), and 4 (10.5%) women, respectively. In multivariate analyses, parity, gestational age, and occupation were not associated with S. mansoni infection, unlike maternal age less than 20 years (odds ratio [OR] 9.8; 95% confidence interval [CI], 1.5-16.3; P=0.01) and no education (OR 6.2; 95% CI, 2.8-12.9; P<0.001). CONCLUSION: There was a high level of S. mansoni infection among pregnant women in the present setting, especially among younger women and those with no education. Control and preventive measures should be used in the area. PMID- 22036061 TI - Assessment of knowledge and stigmatizing attitudes related to human papillomavirus among Hong Kong Chinese healthcare providers. AB - OBJECTIVE: To assess knowledge and stigmatizing attitudes related to human papillomavirus (HPV) and HPV testing among Chinese healthcare providers in Hong Kong. METHODS: Between May and September 2010, an anonymous self-administered questionnaire was sent to 247 doctors, nurses, and smear-taking trainees providing cervical screening in Hong Kong. RESULTS: In total, 137 questionnaires were returned. Most participants had basic knowledge about HPV infection and HPV vaccination. Only about 33% knew that high-risk HPV does not cause genital warts, infection is most common among young women, or infected individuals might not have any identifiable sexual risk factors. Regarding HPV testing, 6 of 7 knowledge items were answered incorrectly by many participants (>= 50%), highlighting a lack of understanding of the indications for HPV testing and the implications of a positive result. About 30% of participants agreed that individuals with HPV infection were sexually easy, responsible for their infection, or had more than 1 sexual partner. More knowledge about HPV infection predicted less stigmatizing attitudes. CONCLUSION: Continued education on HPV and HPV testing is needed for frontline healthcare providers of screening in Hong Kong. The stigmatizing attitudes toward HPV-infected individuals warrant further exploration of the impact of HPV infection on patient care and interventions. PMID- 22036062 TI - Coping strategies adopted by pregnant women in Pakistan to resist spousal violence. PMID- 22036063 TI - Low maternal vitamin D status during pregnancy requires appropriate therapeutic intervention. PMID- 22036064 TI - The structure of posttraumatic psychopathology in veterans attending primary care. AB - This study attempted to extend research indicating that posttraumatic stress disorder (PTSD) factors of Re-experiencing, Avoidance and Hyperarousal are more related to Fear/phobic disorders, while PTSD Dysphoria is more related to Anxious Misery disorders. Trauma exposure, PTSD and comorbidity data for 668 veteran patients were analysed using confirmatory factor analyses and relative strengths of the relationships between PTSD factors and the Fear and Anxious-Misery factors were assessed. Combining Simms, Watson, and Doebbeling's (2002) model of PTSD symptoms and Krueger's (1999) Fear/Anxious Misery model of mood and anxiety disorders fit the data well. Contrary to previous research, PTSD Re-experiencing, Avoidance and Hyperarousal did not correlate more with the Fear factor; nor did PTSD Dysphoria correlate more with Anxious-Misery. Hyperarousal was more closely related to Fear than was Re-experiencing; however, Avoidance was not. Dysphoria was more closely related to the Anxious-Misery factor than all other PTSD factors. PMID- 22036065 TI - Reading the ubiquitin postal code. AB - Polyubiquitin chains are assembled through the formation of an isopeptide bond between a lysine side-chain or terminal amino group of a proximal ubiquitin moiety and the carboxy-terminal of a distal ubiquitin moiety. Protein substrates tagged by polyubiquitin chains of different linkages undergo different fates. Many polyubiquitin chain types have been characterized so far, notably Lys11, Lys48, Lys63 and linear chains. These different types of chains are synthesized, disassembled and recognized by selective enzymes and receptors. Here I survey the structural basis for the selective binding of polyubiquitin chains of specific linkages, with an emphasis on recent advances in our understanding of polyubiquitin chain structure and functions. Recent work suggests linkage-type discrimination by members of the NF-kappab signalling and DNA repair pathways and a specific role for Lys48-linked polyubiquitin chain recognition by proteasome associated proteins. PMID- 22036066 TI - Social factors in the cultural evolution of language. Comment on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22036068 TI - Abstract concepts in language and cognition. Commentary on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22036069 TI - Elevated circulating levels of the serum acute-phase protein YKL-40 (chitinase 3 like protein 1) are a marker of obesity and insulin resistance in prepubertal children. AB - YKL-40 (chitinase 3-like protein 1) is a newly recognized protein that is secreted by activated macrophages and neutrophils and expressed in a broad spectrum of inflammatory conditions and cancers. It has also been associated with endothelial dysfunction and diabetes in adults. Its role in childhood obesity has not been evaluated yet. Our aim was to evaluate the associations of serum YKL-40 levels with markers of obesity, inflammation, and insulin resistance in children. Forty-one obese prepubertal children and 41 age- and sex-matched lean controls were included, and serum YKL-40 levels were determined. Body mass index (BMI), blood pressure (BP), body fat percentage, fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR) index, whole-body insulin sensitivity index, lipids, white blood cell (WBC) count, C-reactive protein, and fibrinogen levels were also assessed. Obese children had higher YKL-40 levels compared with controls (P = .003). Insulin-resistant individuals showed higher YKL-40 compared with non-insulin-resistant individuals after adjusting for age and BMI (adjusted P = .039). Serum YKL-40 levels were positively correlated with age, BMI, body fat percentage, fasting glucose and insulin, HOMA-IR index, whole body insulin sensitivity index, systolic BP, mean BP, and WBC count (P < .05). After adjustment for age, sex, BMI, WBC count, and systolic BP, HOMA-IR index remained significantly associated with YKL-40 levels (P < .001). The study suggests that YKL-40 levels are elevated in obese youth and represent a marker of insulin resistance even in childhood. Prospective studies are needed to determine whether children with elevated YKL-40 levels are at higher risk for future cardiovascular disease. PMID- 22036070 TI - Segmental arterial mediolysis--an iatrogenic vascular disorder induced by ractopamine. AB - BACKGROUND: Segmental arterial mediolysis, an uncommon arterial disorder most often occurring in the splanchnic muscular arteries of the abdomen, is a cause of catastrophic hemorrhages. Its histology and initial clinical presentations suggested that it represented a localized norepinephrine-induced vasospastic response to perturbations in vascular tone and blood volume distribution caused by coexisting vasoconstrictor conditions. However, later presentations were at odds with some aspects of this hypothesis. METHODS: Nine greyhound dogs were administered a single dose of ractopamine. Two dogs developing persistent conduction abnormalities with biochemical evidence of heart injury were euthanized and necropsied--one 4 days and the other 17 days after dosage This report is based on findings and comparisons of the canine abdominal and coronary arteries to segmental arterial mediolysis. RESULTS: Lesions having features of early-injurious-stage segmental arterial mediolysis were identified in the canine arteries 4 days postractopamine, and arteries examined after 17 days showed alterations typically occurring in reparative-stage segmental arterial mediolysis. It is suspected that ractopamine, a Beta-2 adrenergic agonist, created segmental arterial mediolysis by neuromodulating the peripheral sympathetic nervous system to release norepinephrine from varicosities of efferent nerves serving splanchnic arteries that stimulate alpha-1 receptors to induce injury at the adventitial medial junction and medial muscle apoptosis. CONCLUSION: This finding and other cited examples suggest that segmental arterial mediolysis may be a disorder principally caused by iatrogenic or accidental exposure to alpha-1 adrenergic receptor agonists or Beta-2 agonists able to release norepinephrine from the peripheral nervous system. PMID- 22036071 TI - Molecular changes in the heart of a severe case of arrhythmogenic right ventricular cardiomyopathy caused by a desmoglein-2 null allele. AB - INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder caused by mutations in desmosomal genes. It is often associated with life-threatening arrhythmias. Some affected individuals develop progressive heart failure and may require cardiac transplantation. METHODS: The explanted heart of a young adult with end-stage heart failure due to a null allele in desmoglein-2 was studied at macroscopic, microscopic, and molecular level. Myocardial samples were probed for junctional localization of desmosomal components and the gap junction protein connexin43 by immunohistochemical staining. In addition, the protein content of desmosomal and adherens junction markers as well as connexin43 was assessed by Western blotting. RESULTS: Histological analysis confirmed ARVC. Despite the loss of specific immunoreactive signal for desmosomal components at the cardiac intercalated disks (shown for plakoglobin, desmoplakin, and plakophilin-2), these proteins could be detected by Western blotting. Only for desmoglein-2, desmocollin-2, and plakoglobin were reduced protein levels observed. Adherens junction proteins were not affected. Lower phosphorylation levels were observed for connexin43; however, localization of the gap junction protein displayed regional differences. At the molecular level, disease progression was more severe in the right ventricle compared to the left ventricle. CONCLUSION: Our data suggest that, in the ARVC heart, plakoglobin is mainly redistributed from the junctions to other cellular pools and that protein degradation only plays a secondary role. Homogenous changes in the phosphorylation status of connexin43 were observed in multiple ARVC samples, suggesting that this might be a general feature of the disease. PMID- 22036072 TI - Single gene disorders of the aortic wall. AB - Genetic diseases that affect the vasculature primarily affect the aortic root and ascending aorta. These conditions lead to aortic root dilatation, which, if not treated, will result in dissection and death. Often, aortic disease is just one manifestation of a syndrome with diverse findings. Some of these diseases were described over 100 years ago based on physical manifestations, and their causative genes are among the first described Mendelian causes of cardiovascular disease. Within the pediatric and young adult population, there are over 15 causes of ascending aortic disease. Previously, these diverse diseases, along with their histopathology, have been extensively characterized. Most genetic causes of root aneurysm are extremely rare. Amongst these, five diseases are relatively common with known genetic mutations for which pathologists should be familiar. These are Marfan syndrome, vascular Ehlers-Danlos syndrome, Loeys-Dietz syndrome, Turner syndrome, and familial thoracic aneurysm and dissection. This review will focus on these important causes of genetic aortic disease. The aim is to briefly describe the historical record and physical manifestations and then focus on cardiovascular complications, the causative genes, and current research into these entities. PMID- 22036073 TI - Ionic liquid/water interfacial localization of a green fluorescent protein fused to a tryptophan-rich peptide. AB - We report that several tryptophan-rich peptides exhibit an affinity for a hydrophobic ionic liquid (IL) (1-ethyl-3-methylimidazolium bis trifluoromethanesulfonyl imide), and that green fluorescent protein (GFP) fused to a peptides, "SSSWWSWWWW" (SW1) or "SWWWWSWWWW" (SW2), containing serine (S) and tryptophan (W) at the C terminus localized at the IL/water interface. While GFPs without W-rich peptide distributed only in water phase, SW1- and SW2-GFPs were accumulated at the interface. The localization of SW1-GFP showed biphasic behavior, and most distinctive localization was observed at 7.1 MUM. The localization of SW2-GFP presumably occurred at largely lower concentration (<=0.5 MUM) than that of SW1-GFP, which difference was due to the higher hydrophobicity of SW2 peptide. PMID- 22036074 TI - Biosurfactant-producing bacterium, Pseudomonas aeruginosa MA01 isolated from spoiled apples: physicochemical and structural characteristics of isolated biosurfactant. AB - An extensive investigation was conducted to isolate indigenous bacterial strains with outstanding performance for biosurfactant production from different types of spoiled fruits, food-related products and food processing industries. An isolate was selected from 800 by the highest biosurfactant yield in soybean oil medium and it was identified by 16S rRNA and the two most relevant hypervariable regions of this gene; V3 and V6 as Pseudomonas aeruginosa MA01. The isolate was able to produce 12 g/l of a glycolipid-type biosurfactant and generally less efficient to emulsify vegetable oils compared to hydrocarbons and could emulsify corn and coconut oils more than 50%. However, emulsification index (E(24)) of different hydrocarbons including hexane, toluene, xylene, brake oil, kerosene and hexadecane was between 55.8% and 100%. The surface tension of pure water decreased gradually with increasing biosurfactant concentration to 32.5 mNm(-1) with critical micelle concentration (CMC) value of 10.1mg/l. Among all carbon substrates examined, vegetable oils were the most effective on biosurfactant production. Two glycolipid fractions were purified from the biosurfactant crude extracts, and FTIR and ES-MS were used to determine the structure of these compounds. The analysis indicated the presence of three major monorhamnolipid species: R(1)C(10)C(10), R(1)C(10)C(12:1), and R(1)C(10)C(12); as well as another three major dirhamnolipid species: R(2)C(10)C(10), R(2)C(10)C(12:1), and R(2)C(10)C(12). The strain sweep experiment for measuring the linear viscoelastic of biosurfactant showed that typical behavior characteristics of a weak viscoelastic gel, with storage modulus greater than loss modulus at all frequencies examined, both showing some frequency dependence. PMID- 22036075 TI - Ralstonia sp. U2 naphthalene dioxygenase and Comamonas sp. JS765 nitrobenzene dioxygenase show differences in activity towards methylated naphthalenes. AB - Methylsubstituted naphthalenes constitute a significant part of light gas oil fractions (LGO). These are toxic compounds with low fuel value, and can potentially be enzymatically modified to increase the fuel value and at the same time reduce toxicity. The first step in the biodegradation of naphthalene involves dioxygenation of the aromatic ring catalysed by naphthalene dioxygenase (NDO). Here we show that recombinantly produced NDO from Ralstonia sp. U2 and the related nitrobenzene dioxygenase (NBDO) from Comamonas sp. JS765 can use several mono-, di-, tri-, and tetramethylated naphthalenes as substrates. For the majority of the substrates both enzymes catalyse the formation of a mixture of mono- and dioxygenated products, and it is only dioxygenated products that are likely to be processed further, leading to ring cleavage. In some cases, like for 1-methylnaphthalene, NDO mainly generates the monooxygenated form, while with NBDO, the dioxygenated form dominates. In other cases, as for 1,4 dimethylnaphthalene, the monooxygenated product dominates with NDO, whereas NBDO generates similar amounts of both forms. Presumably, the best future strategy for bioconversion of methylated naphthalenes in LGO is to develop engineered enzyme that are optimised with respect to the specific composition of naphthalene derivatives found in a given product. PMID- 22036076 TI - Modelling of growth, growth/no-growth interface and nonthermal inactivation areas of Listeria in foods. AB - Growth, growth boundary and inactivation models have been extensively developed in predictive microbiology and are commonly applied in food research nowadays. Few studies though report the development of models which encompass all three areas together. A tiered modelling approach, based on the Gamma hypothesis, is proposed here to predict the behaviour of Listeria. Datasets of Listeria spp. behaviour in laboratory media, meat, dairy, seafood products and vegetables were collected from literature, unpublished sources and from the databases ComBase and Sym'Previus. The explanatory factors were temperature, pH, water activity, lactic and sorbic acids. For the growth part, 697 growth kinetic datasets were fitted. The estimated growth rates and 2021 additional growth primary datasets were used to fit the secondary growth models. In a second step, the fitted model was used to predict the growth/no-growth boundary. For the inactivation modelling phase, 535 inactivation curves were used. Gamma models with and without interactions between the explanatory factors were used for the growth and boundary models. The correct prediction percentage (predicted growth when growth is observed+predicted inactivation when inactivation is observed) varied from 62% to 81% for the models without interactions, and from 85% to 87% for the models with interactions. The median error for the predicted population size was less than 0.34 log(10)(CFU/mL) for all models. The kinetics of inactivation were fitted with modified Weibull primary models and the estimated bacterial resistance was then modelled as a function of the explanatory factors. The error for the predicted microbial population size was less than 0.71 log(10)(CFU/mL) with a median value of less than 0.21 for all foods. The model enables the quantification of the increase or decrease in the bacterial population for a given formulation or storage condition. It might also be used to optimise a food formulation or storage condition in the case of a targeted increase or decrease of the bacterial population. PMID- 22036077 TI - A single method for recovery and concentration of enteric viruses and bacteria from fresh-cut vegetables. AB - Fresh-cut vegetables are prone to be contaminated with foodborne pathogens during growth, harvest, transport and further processing and handling. As most of these products are generally eaten raw or mildly treated, there is an increase in the number of outbreaks caused by viruses and bacteria associated with fresh vegetables. Foodborne pathogens are usually present at very low levels and have to be concentrated (i.e. viruses) or enriched (i.e. bacteria) to enhance their detection. With this aim, a rapid concentration method has been developed for the simultaneous recovery of hepatitis A virus (HAV), norovirus (NV), murine norovirus (MNV) as a surrogate for NV, Escherichia coli O157:H7, Listeria monocytogenes and Salmonella enterica. Initial experiments focused on evaluating the elution conditions suitable for virus release from vegetables. Finally, elution with buffered peptone water (BPW), using a Pulsifier, and concentration by polyethylene glycol (PEG) precipitation were the methods selected for the elution and concentration of both, enteric viruses and bacteria, from three different types of fresh-cut vegetables by quantitative PCR (qPCR) using specific primers. The average recoveries from inoculated parsley, spinach and salad, were ca. 9.2%, 43.5%, and 20.7% for NV, MNV, and HAV, respectively. Detection limits were 132 RT-PCR units (PCRU), 1.5 50% tissue culture infectious dose (TCID50), and 6.6 TCID50 for NV, MNV, and HAV, respectively. This protocol resulted in average recoveries of 57.4%, 64.5% and 64.6% in three vegetables for E. coli O157:H7, L. monocytogenes and Salmonella with corresponding detection limits of 103, 102 and 103 CFU/g, respectively. Based on these results, it can be concluded that the procedure herein is suitable to recover, detect and quantify enteric viruses and foodborne pathogenic bacteria within 5 h and can be applied for the simultaneous detection of both types of foodborne pathogens in fresh-cut vegetables. PMID- 22036079 TI - Modafinil treatment prevents REM sleep deprivation-induced brain function impairment by increasing MMP-9 expression. AB - Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats. PMID- 22036080 TI - Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3beta decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model. AB - Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3beta (p-GSK3beta) and total GSK3beta levels were determined, and importantly GSK3beta regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3beta levels, while total GSK3beta did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3beta levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3beta levels in neither the hippocampus nor PFC. Total GSK3beta levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3beta levels, a kinase key of signaling cascade of insulin receptor. PMID- 22036081 TI - Influence of time to achieve substrate distribution equilibrium between brain tissue and blood on quantitation of the blood-brain barrier P-glycoprotein effect. AB - Active efflux transport processes at the blood-brain barrier (BBB), such as P glycoprotein (P-gp)-mediated efflux, can limit brain uptake of therapeutics. Accurate determination of the consequent impact on brain uptake is assumed to require sampling post-attainment of brain-to-blood distribution equilibrium. Because this approach is not always feasible, understanding the relationship between apparent degree of efflux (e.g., calculated BBB P-gp effect) and the fraction of time remaining until distribution equilibrium is achieved (FTDE) would be advantageous. This study employed simulation strategies to explore this relationship in the simplest relevant system (absence of protein binding, saturable uptake, or metabolism at the BBB). Concentration-time profiles were simulated with a 4-compartment system (blood, peripheral tissues, BBB endothelium and brain parenchyma). A unidirectional endothelium-to-blood rate constant, PS(e), represented P-gp-mediated efflux. A parameter space was selected to simulate an 18-fold P-gp effect, (K(p,brain) at distribution equilibrium in the absence [K(p,brain)=82] vs. presence [K(p,brain)=4.5] of P-gp-mediated flux), as observed for paclitaxel in P-gp-deficient vs. P-gp-competent mice. Hypothetical compounds with different P-gp effects, peripheral compartment distribution kinetics, or times to achieve distribution equilibrium were simulated by perturbing the values of relevant model parameters. P-gp effects calculated prior to attainment of distribution equilibrium may be substantially erroneous. However, reasonably accurate estimates can be obtained relatively early in the net distributional phase (under 20% error at FTDE>0.36 or 0.11 for bolus or infusion administration, respectively). Potential errors associated with non equilibrium calculations are dependent on both P-gp-mediated and P-gp-independent components of flux across the BBB. PMID- 22036082 TI - Emetine treatment masks initial LTP without affecting long-term stability. AB - Applying emetine, a protein synthesis inhibitor, at 20-40MUM for 90-120 min prior to LTP induction in hippocampal slices from young rats (2-3 weeks) and washing it out afterwards revealed a slowly developing potentiation that reached maximum after 20-30 min, distinct from the LTP observed under normal conditions. Nevertheless, the later phase of this potentiation was similar to standard LTP as judged by experiments lasting up to 8h after induction. Emetine preapplication for 3h without subsequent washout resulted in a substantial decay of evoked responses. By comparison between test and control pathways, LTP could still be assessed in these experiments for up to 4-6h after induction and was found not to differ from normal, except for the slow onset. The NMDA-R blocker AP5 fully blocked LTP; however, with emetine pretreatment there was an initial depression of responses with a gradual recovery during 20-30 min. This depression involved not only the field EPSP but also the presynaptic fiber volley. However, when using the protein synthesis inhibitors cycloheximide and anisomycin there was essentially no such depression. In conclusion, the present results support the idea that preexisting proteins are sufficient for inducing stable LTP. Moreover, emetine but not anisomycin or cycloheximide impairs presynaptic action potentials, leading to an apparent slow onset of LTP. The emetine-dependent effect could be due to a characteristic blocking spectrum of the drug, preferred targeting of presynaptic compartments or effects unrelated to protein synthesis. PMID- 22036083 TI - Craniofacial morphology of Homo floresiensis: description, taxonomic affinities, and evolutionary implication. AB - This paper describes in detail the external morphology of LB1/1, the nearly complete and only known cranium of Homo floresiensis. Comparisons were made with a large sample of early groups of the genus Homo to assess primitive, derived, and unique craniofacial traits of LB1 and discuss its evolution. Principal cranial shape differences between H. floresiensis and Homo sapiens are also explored metrically. The LB1 specimen exhibits a marked reductive trend in its facial skeleton, which is comparable to the H. sapiens condition and is probably associated with reduced masticatory stresses. However, LB1 is craniometrically different from H. sapiens showing an extremely small overall cranial size, and the combination of a primitive low and anteriorly narrow vault shape, a relatively prognathic face, a rounded oval foramen that is greatly separated anteriorly from the carotid canal/jugular foramen, and a unique, tall orbital shape. Whereas the neurocranium of LB1 is as small as that of some Homo habilis specimens, it exhibits laterally expanded parietals, a weak suprameatal crest, a moderately flexed occipital, a marked facial reduction, and many other derived features that characterize post-habilis Homo. Other craniofacial characteristics of LB1 include, for example, a relatively narrow frontal squama with flattened right and left sides, a marked frontal keel, posteriorly divergent temporal lines, a posteriorly flexed anteromedial corner of the mandibular fossa, a bulbous lateral end of the supraorbital torus, and a forward protruding maxillary body with a distinct infraorbital sulcus. LB1 is most similar to early Javanese Homo erectus from Sangiran and Trinil in these and other aspects. We conclude that the craniofacial morphology of LB1 is consistent with the hypothesis that H. floresiensis evolved from early Javanese H. erectus with dramatic island dwarfism. However, further field discoveries of early hominin skeletal remains from Flores and detailed analyses of the finds are needed to understand the evolutionary history of this endemic hominin species. PMID- 22036084 TI - Chromatographic sample collection from two-phase (gas+liquid) flows. AB - A particularly challenging sample presentation in analytical chemistry is a flowing stream that consists of both a gas and liquid phase, combined with the common situation in which a reliable analysis is needed for both phases, separately. In these cases, the vapor and liquid must be physically separated (without change to either), before the individual phases can be collected and analyzed. It is not possible to analyze two-phase flows otherwise. Although the two phases are at equilibrium, it is imperative that no liquid contaminate the vapor, and no vapor be entrained in the liquid at a given temperature and pressure. In this paper, we describe a simple on-line device that can individually separate and collect the vapor and liquid phases of a two-phase flow. The apparatus, which we call P(2)SC, uses an adaptation of the branch point separator, with vapor collection done downstream in a metal bellows. The liquid collection is done in a length of Teflon tube. The separated vapor and liquid phases are then easily transferred into any desired analytical instrument with a syringe, although any sample introduction method, such as a valve, could be used as well. We discuss the application of this device with a stream of thermally stressed rocket kerosene. PMID- 22036085 TI - Effect of reaction solvent on the preparation of thermo-responsive stationary phase through a surface initiated atom transfer radical polymerization. AB - Poly(N-isopropylacrylamide) (PIPAAm) brush grafted silica beads, a thermo responsive chromatographic stationary phase, were prepared through a surface initiated atom transfer radical polymerization (ATRP) using 2-propanol, N,N dimethylformamide (DMF), and water as reaction solvents. The rate of grafting PIPAAm on silica bead surfaces was different and found to be dependent on the reactivity of reaction solvent. Temperature-dependent elution profiles of hydrophobic steroids from the prepared-beads-packed columns were found to be different, although the graft amounts of PIPAAm were similar on silica bead surfaces. Especially, prepared beads using 2-propanol exhibited a higher resolution than those using DMF. Calibration curves using glucose and pullulan suggested that beads prepared using DMF prohibited analytes to diffuse into the pores. On the contrary, beads prepared using 2-propanol allowed analytes to diffuse into the pores. The pore diameter of the prepared beads, measured by N(2) adsorption-desorption measurement, suggested that beads using 2-propanol has relatively larger pore diameter than those using DMF. Thus, the reaction solvent in surfaces-initiated ATRP affected the grafting configuration of PIPAAm on porous silica-bead surfaces, leading to the different separation efficiency of stationary phase for bioactive compounds. PMID- 22036086 TI - Correlations between conformational isomerism and chromatographic diastereoselectivity of bis amino amide s-triazine derivatives. AB - NMR spectroscopy was used to probe the conformational behavior of diastereomeric s-triazine derivatives containing two chiral amino amide substituents, in order to shed light onto the mechanism of chromatographic diastereoselectivity. Utilizing the amino hydrogen signals in the proton NMR spectrum, the population of the conformations caused by rotation about the bond between the amino nitrogen and aromatic carbon atoms could be observed. The population distribution between the three possible conformations was similar but not identical between the two diastereomers, with similar trends being observed for both bis alanine amide and bis valine amide derivatives. Based on a simple model in which it is assumed that adsorption to the hydrophobic RP-LC stationary phase occurs only for the conformations having both amino amide R-groups on the same side of the triazine ring plane, the different conformation populations between the two diastereomers obtained by NMR was consistent with the observed RP-LC elution order (L-L diastereomer followed by L-D). The predicted diastereoselectivity values from NMR data were compared to RP-LC diastereoselectivity values obtained using both C18 and polymeric columns, with both acetonitrile/water and DMSO/water mobile phases. Values obtained with the polymeric column were in better agreement with calculated values than those obtained with the C18 column, suggesting that the simple adsorption model used to calculate the diastereoselectivity is more relevant towards a simple hydrophobic polymeric surface rather than a more complex C18 stationary phase. This study indicates that proton NMR is a useful tool for studying the diastereoselective mechanism of these derivatives, due to the relatively slow C-N bond rotation caused by the significant sp(2) character of the amino nitrogen atoms. PMID- 22036087 TI - Analysis of metallothionein by capillary electrophoresis. AB - Metallothioneins (MTs) belong to proteins playing a key role in metal ion homeostasis, maintenance of the redox pool and free radical scavenging in both prokaryotic and eukaryotic cells. Strong interactions of the MTs with essential and non-essential metal ions as well as unique MT structure and behavior under various conditions are subjects of numerous studies. Among other analytical techniques, capillary electrophoresis (CE) has been proven to be an effective tool not only for determination of MT in biological samples, but also for the identification of its isoforms and sub-isoforms in various types of samples. Moreover, CE has a great potential to investigate MT-metal and MT-protein interactions, which has not been fully utilized yet. Thus, it is not surprising that numerous studies devoted to the optimization of CE conditions such as background electrolyte composition, electrolyte modifiers and/or capillary surface modifications have been carried out since MT's discovery in 1957. From the MTs' detection point of view, optical detectors including absorbance, laser induced fluorescence have been employed. Also mass spectrometric detection coupled to the various ionization techniques including inductively coupled plasma (ICP) and electrospray ionization (ESI) has been utilized for detail MT characterization and sensitive determination. In this paper, articles published from eighties to 2011 are reviewed, presenting both optimization of key parameters of CE method for MT determination as well as utilization of CE as a routine analytical technique for further investigation of complex biological and biochemical processes where MT is a key component. PMID- 22036088 TI - Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: a report from the European Osteosarcoma Intergroup. AB - AIM: Chemotherapy-induced toxicity is an independent prognostic indicator in several cancers. We aimed to determine whether toxicity was related to survival and histological response in high-grade localised extremity osteosarcoma. We undertook a retrospective analysis of patients treated within three consecutive randomised controlled trials (RCTs) of the European Osteosarcoma Intergroup. METHODS: Between 1982 and 2002, 533 patients were randomised to six cycles of doxorubicin 75 mg/m(2) and cisplatin 100 mg/m(2). Toxicity data were collected prospectively and graded according to the World Health Organisation (WHO) criteria. Standard univariate and multivariate models were constructed to examine the relationship between reported toxicity, survival, and histological response. RESULTS: Five- and 10-year overall survival was 57% (95% confidence interval (CI) 52-61%) and 53% (49-58%), respectively. Grades 3-4 oral mucositis (hazard ratio (HR) 0.51, 95% CI 0.29-0.91), grades 1-2 nausea/vomiting (HR 0.37, 95% CI 0.16 0.85), grades 1-2 thrombocytopenia (HR 0.49, 95% CI 0.27-0.87), good histological response (HR 0.42, 95% CI 0.27-0.65), and distal tumour site (HR 0.45, 95% CI 0.28-0.71) were associated with improved survival in multivariate analysis. The only factors that were independently associated with histological response were older age (odds ratio (OR) 0.18, 95% CI 0.04-0.72) and chondroblastic tumour (OR 0.28, 95% CI 0.10-0.77), both being associated with a significantly lower chance of achieving a good response. CONCLUSION: Chemotherapy-induced toxicity predicts survival in patients with localised extremity osteosarcoma. Investigation of the pharmacogenomic mechanisms of constitutional chemosensitivity underlying these observations will present opportunities for personalising treatment and could lead to improved outcomes. PMID- 22036089 TI - Establishing an EGFR mutation screening service for non-small cell lung cancer - sample quality criteria and candidate histological predictors. AB - INTRODUCTION: EGFR screening requires good quality tissue, sensitivity and turn around time (TAT). We report our experience of routine screening, describing sample type, TAT, specimen quality (cellularity and DNA yield), histopathological description, mutation result and clinical outcome. METHODS: Non-small cell lung cancer (NSCLC) sections were screened for EGFR mutations (M+) in exons 18-21. Clinical, pathological and screening outcome data were collected for year 1 of testing. Screening outcome alone was collected for year 2. RESULTS: In year 1, 152 samples were tested, most (72%) were diagnostic. TAT was 4.9 days (95%confidence interval (CI)=4.5-5.5). EGFR-M+ prevalence was 11% and higher (20%) among never-smoking women with adenocarcinomas (ADCs), but 30% of mutations occurred in current/ex-smoking men. EGFR-M+ tumours were non-mucinous ADCs and 100% thyroid transcription factor (TTF1+). No mutations were detected in poorly differentiated NSCLC-not otherwise specified (NOS). There was a trend for improved overall survival (OS) among EGFR-M+ versus EGFR-M- patients (median OS=78 versus 17 months). In year 1, test failure rate was 19%, and associated with scant cellularity and low DNA concentrations. However 75% of samples with poor cellularity but representative of tumour were informative and mutation prevalence was 9%. In year 2, 755 samples were tested; mutation prevalence was 13% and test failure only 5.4%. Although samples with low DNA concentration (<2 ng/MUL) had more test failures (30% versus 3.9% for [DNA]>2.2 ng/MUL), the mutation rate was 9.2%. CONCLUSION: Routine epidermal growth factor receptor (EGFR) screening using diagnostic samples is fast and feasible even on samples with poor cellularity and DNA content. Mutations tend to occur in better differentiated non-mucinous TTF1+ ADCs. Whether these histological criteria may be useful to select patients for EGFR testing merits further investigation. PMID- 22036090 TI - Evolutionary origin of bipolar disorder-revised: EOBD-R. AB - The hypothesis of the evolutionary origin of bipolar disorder (EOBD) synthesized ideas about the biological clock and seasonal shifts in mood (Rosenthal, Wehr) with theorizing that bipolar disorder descends from a pyknic (compact, cold adapted) group (Kretchmer). The hypothesis suggested that bipolar behaviors evolved in the northern temperate zone as highly derived adaptations to the selective pressures of severe climatic conditions during the Pleistocene. Given evidence of Neandertal contributions to the human genome, the hypothesis is extended (EOBD-R) to suggest Neandertal as the ancestral source for bipolar vulnerability genes (susceptibility alleles). The EOBD-R hypothesis explains and integrates existing observations: bipolar disorder has the epidemiology of an adaptation; it is correlated with a cold-adapted build, and its moods vary according to light and season. Since the hypothesis was first published, data consistent with it have continued to appear. Individuals with seasonal affective disorder, which is related to bipolar disorder, have been shown to manifest a biological signal of season change similar to that found in hibernating animals. The involvement of the circadian gene network in the pathophysiology of bipolar disorder has been confirmed. Because selective pressures during the Pleistocene would have been greatest for women of reproductive age, they are expected to manifest winter depression more than males or younger females, which is the case. (This sex difference is also found in hibernating mammals.) Because it is hypothesized that the evolution of bipolar disorder took place in the northern temperate zone during the Pleistocene, it is not expected that individuals of African descent, lacking Neandertal genes, will manifest circular bipolar I disorder, and in fact, the incidence of bipolar disorder among black individuals is less than among whites. A definitive test of the hypothesis is proposed: It is predicted that the bipolar and Neandertal genomes will be more similar than the modern human and Neandertal genomes, and the modern human and San and Yoruba genomes will be more similar than the bipolar and San and Yoruba genomes. Failure to confirm these predictions will falsify the EOBD-R hypothesis. The EOBD-R hypothesis has important implications in the search for bipolar vulnerability genes and our understanding of ourselves and our Neandertal ancestor. At a practical level, confirmation of the EOBD-R hypothesis will boost interest and research in the prevention and management of bipolar symptoms by manipulation of ambient light. PMID- 22036091 TI - Might the inability to feel pleasure (anhedonia) explain the symptoms of major depression and schizophrenia, including unmotivated anxiety, delusions and hallucinations? AB - Inability to enjoy normally pleasurable experiences (anhedonia) is a symptom common both to major depression and schizophrenia. It also regularly accompanies and follows stress, and its presence in the two mental illnesses could depend on the fact that both are facilitated and often preceded by stressful events. Anhedonia might possibly accompany stress because the loss of the pleasure of aiming for a goal and achieving it (including defending oneself and escaping from a danger) could lead to immobility, and immobility (playing dead) offers the extreme chance of safety when an animal is facing the worst possible stressful situation--being seized by a predator--as in this case any movement can further stimulate the predator's aggressiveness. Perceiving and connecting sensory information also gives pleasure, and this appears to enhance the clarity of sensations and is an important factor in learning. We propose that anhedonia, by reducing or eliminating the pleasure, might jeopardize the usual appearance of the environment, which must not only be clearly perceived but also continuously interpreted (for instance a foreshortening, or something far off seen as small, must not be seen as a real deformation; the same holds for words, where the meaning has to be grasped from the single letters, and so on). Consequently, anhedonia could in some cases make the environment's image strange, distorted and frightening, and this could cause anxiety, confusion, and give problems in contacts with people and things. As correct information about images and sounds can inhibit visual and auditory hallucinations (considering them, like delusions, as attempts to reconstruct and make sense again of a world that is becoming confused and alien), we propose that anhedonia, interfering with the correct perceiving and processing of sensations, may facilitate them. PMID- 22036092 TI - Dopamine sudden depletion as a model for mixed depression. AB - Up to date research on Bipolar Disorders' phenomenology is in keeping with early descriptions made by E. Kraepelin regarding the overlap in clinical presentation of both manic and depressive symptoms, namely, mixed states. The latter constitute a highly prevalent and characteristic clinical presentation of Bipolar Disorders' and entail therapeutic difficulties, prognostic implications and increased suicidal risk. Notwithstanding, mixed states', more specifically mixed depression, have been underestimated and bypassed to the point where currently neither diagnostic criteria nor specific therapeutic recommendations are provided. In addition to the lack of agreement on nosography and diagnostic criteria, mixed depression is usually excluded from Bipolar Disorders' neurobiological models. Furthermore, renewed interest in the role of dopamine in Bipolar Disorders' physiopathology has left aside hypothesis that may account for the aforementioned clinical presentation. Interestingly enough, other syndromes arising from sudden dopamine depletion such as neuroleptic dysphoria or withdrawal syndromes from dopaminergic drugs, bear remarkable clinical similarities with mixed depression. These syndromes have been subject of further research and may thus provide a model for mixed states' physiopathology. Indeed, this article accounts for clinical similarities between mixed depression, neuroleptic induced dysphoria, and other behavioural syndromes arising from sudden dopamine depletion. After reviewing neurochemical basis of such syndromes we present, to the best of our knowledge, the first neurobiological hypothesis for mixed depression. Specifically, such hypothesis regards over activation symptoms as auto regulatory attempts to compensate for sudden dopaminergic depletion. This hypothesis provides with a beginning step for the neglected problem of mixed depression, a non-antithetic link between the dopaminergic hypothesis for both manic and depressive symptoms, a plausible explanation regarding inter individual variability to mixed depression susceptibility, and suggests new approaches for the development of novel treatments in which dopamine dysregulation should be targeted. PMID- 22036093 TI - Special features of right bundle branch block in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. AB - We searched for special features in patients with complete and incomplete right bundle branch block diagnosed as having arrhythmogenic right ventricular cardiomyopathy/dysplasia. Whether right bundle branch block is a frequent finding in arrhythmogenic right ventricular cardiomyopathy should be studied. The question is whether special features exist such as T-wave inversions, localized right precordial QRS prolongation and r'/s ratio<1. RESULTS: ARVC could be diagnosed according to ISFC/ESC criteria in 374 patients. CRBBB was found in 22 cases (6%) and iCRBBB was present in 47 cases (12.5%). In CRBBB T wave inversions >= V4 was found in 10 cases (n.s.) and r'/s ratio<1 was present in 12 cases (p<0.001). In iCRBBB T wave inversions >= V4 was found in 10 cases (n.s.) and ST segment elevation in right precordial leads was present in 19 cases (p<0.005). In all patients with ARVC localized right precordial QRS prolongation was found. Patients with CRBBB have a bad prognosis: 17 of 22 patients developed biventricular heart failure requiring heart transplantation and diuretic therapy. CONCLUSIONS: CRBBB and iCRBBB are infrequent findings in arrhythmogenic right ventricular cardiomyopathy. Complete right bundle branch block is characterized by r'/s ratio<1. There are no significant T wave inversions >= V4. Incomplete right bundle branch block is characterized by ST segment elevation in right precordial leads but not by T wave inversions >= V4. PMID- 22036094 TI - New insights into the natural history of asthma: primary prevention on the horizon. AB - Recent studies of the natural history of asthma have shifted attention toward viral respiratory tract illness in early life as a major risk factor associated with the development of the most persistent forms of the disease. Although early aeroallergen sensitization is strongly associated with chronic asthma, several trials in which single-aeroallergen exposure in pregnancy and early childhood was successfully accomplished and compared with sham avoidance have failed to show any decrease in asthma incidence. New evidence suggests that complex interactions occur between viral infection and aeroallergen sensitization in genetically susceptible subjects that trigger the immune responses and airway changes that are characteristic of persistent asthma. The finding that exposure to bacterial products among children raised on farms is associated with diminished asthma prevalence during the school years has now been replicated, and experimental studies have suggested that these effects are mediated by the activation of regulatory T cells in the airway. It is thus plausible to hypothesize that primary prevention of asthma could be attained through surrogate therapeutic interventions that activate similar mechanisms in young children at high risk for asthma. PMID- 22036096 TI - A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. AB - BACKGROUND: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. OBJECTIVE: We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. METHOD: Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). RESULTS: Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P(grass) = 1.6 * 10(-9); P(AR) = 8.0 * 10(-3)). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P(grass) = 9.4 * 10(-9); P(AR) = 3.8 * 10(-8)). The third genome-wide significant variant was rs17513503 (P(grass) = 1.2 * 10(-8); PAR = 7.4 * 10(-7)) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype. CONCLUSIONS: This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. PMID- 22036097 TI - Tissue remodeling in patients with eosinophilic esophagitis: what lies beneath the surface? PMID- 22036098 TI - Exertional dyspnea and inspiratory stridor of 2 years' duration: a tale of 2 wheezes. PMID- 22036099 TI - [The discovery of insulin: continued controversies after ninety years]. PMID- 22036100 TI - Differential effects of low-carbohydrate and low-fat diets on inflammation and endothelial function in diabetes. AB - OBJECTIVE: To characterize acute (postprandial) and chronic (after a 6-month period of weight loss) effects of a low-carbohydrate vs. a low-fat diet on subclinical markers of cardiovascular disease (CVD) in adults with type 2 diabetes. DESIGN: At baseline and 6 months, measures of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule (sICAM) and soluble E-selectin were obtained from archived samples (n = 51) of participants randomized in a clinical trial comparing a low-carbohydrate and a low-fat diet. In a subset of participants (n = 27), postprandial measures of these markers were obtained 3 h after a low-carbohydrate or low-fat liquid meal. Endothelial function was also measured by reactive hyperemic peripheral arterial tonometry during the meal test. Paired t tests and unpaired t tests compared within- and between-group changes. RESULTS: There were no significant differences observed in postprandial measures of inflammation or endothelial function. After 6 months, CRP (mean +/- S.E.) decreased in the low-fat arm from 4.0 +/- 0.77 to 3.0 +/- 0.77 (P = .01). In the low-carbohydrate arm, sICAM decreased from 234 +/- 22 to 199 +/- 23 (P = .001), and soluble E-selectin decreased from 93 +/- 10 to 82 +/- 10 (P = .05.) A significant correlation between change in high-density lipoprotein and change in soluble E-selectin (r = -0.33, P = .04) and with the change in ICAM (r = -0.43, P = .01) was observed. CONCLUSIONS: Low-carbohydrate and low-fat diets both have beneficial effects on CVD markers. There may be different mechanisms through which weight loss with these diets potentially reduces CVD risk. PMID- 22036101 TI - Gold nanoparticles surface-functionalized with paclitaxel drug and biotin receptor as theranostic agents for cancer therapy. AB - We describe in this study whether the gold nanoparticle (AuNP) surface functionalized with PEG, biotin, paclitaxel (PTX) and rhodamine B linked beta cyclodextrin (beta-CD) (AuNP-5') can be useful as a theranostic agent for cancer therapy without the cytotoxic effect on normal cells. Prior to surface functionalizing AuNPs, the cytotoxicity of the nanoparticles was evaluated, followed by their cytocompatibility. PTX, an anti-cancer agent, formed inclusion complexations with beta-CD conjugated AuNPs, and effectively released from the AuNP-2' surface-functionalized with PEG, beta-cyclodextrin (beta-CD) and paclitaxel (PTX) using the intracellular glutathione (GSH) level (10 mm). Two types of AuNP-4 surface-functionalized with PEG and rhodamine B linked beta-CD and AuNP-5 surface-functionalized PEG, biotin and rhodamine B linked beta-CD were used for evaluating their specific interaction on cancer cells such as HeLa, A549 and MG63. These were also tested against normal NIH3T3 cell, determining that the AuNP-5 was more effectively involved with the cancer cells. Confocal laser scanning microscopy (CLSM), fluorescence-activated cell-sorting (FACS) and cell viability analyses showed that the AuNP-5' plays a significant role in the diagnosis and therapy of the cancer cells, and may be used in theranostic agents. PMID- 22036102 TI - Regulation of cell proliferation by multi-layered phospholipid polymer hydrogel coatings through controlled release of paclitaxel. AB - We fabricated multi-layered hydrogels on titanium alloy (Ti) surfaces by applying alternating layers of a water-soluble phospholipid polymer (PMBV) and polyvinyl alcohol (PVA). This was accomplished by a layer-by-layer (LbL) process that is based on the formation of reversible covalent bonds between the boronic acid subunits in the PMBV and the hydroxyl groups in the PVA. When placed in an aqueous medium, PMBV acquires a polymeric aggregate structure with hydrophobic domains that can effectively solubilize hydrophobic molecules such as the anticancer drug paclitaxel (PTX) used in this study. The PTX-containing PMBV layer acted as a reservoir in the multi-layered hydrogels. To obtain diverse release profiles, the PTX was loaded in either the top layer (top-type) or the bottom layer (bottom-type) of the hydrogels; additional layers of PMBV and PVA, without PTX, functioned as a diffusion-barrier. In cell culture experiments, top type hydrogels demonstrated excessive suppression of human epidermal carcinoma A431 cell proliferation over 5 days due to the initial high concentration of released PTX. However, bottom-type hydrogels were able to maintain a constant cell number profile. The release of PTX from multi-layered hydrogels was governed by both diffusion through the diffusion-barrier and dissociation of the hydrogel through an exchange reaction of phenylboronic acid subunits with the low molecular weight D-glucose in the cell culture medium. In the cell culture experiments, the cell cycle was arrested in S and G2/M phases, as expected following PTX-mediated growth inhibition; control hydrogels did not demonstrate any appreciable cell cycle arrest. We concluded that cell proliferation could be controlled by the concentration of PTX released from the multi-layered hydrogels prepared through the LbL process. This system when used to solubilize bioactive agents at an appropriate layer within the hydrogel has potential for localized and surface-mediated delivery of bioactive molecules from biomedical devices. PMID- 22036103 TI - The impact of causal attributions on diagnosis and successful referral of depressed patients in primary care. AB - Despite growing concerns of over-treatment, the under-diagnosis and undertreatment of major depressive disorders is still prevalent. Causal attributions are thought to be involved in help seeking behavior, time to diagnosis and the chance for successful referral. Yet, little is known about the extent to which these processes are influenced by causal attributions. 120 patients, involved in the nationwide second Dutch National Survey of General Practice (Schellevis, Westert, & Bakker, 2005), with a current DSM-IV diagnosis of depression, severe depression or with a depression lasting over six months, completed a causal attributions inventory. Demographic and clinical data from the survey, and causal attribution scores were used as independent variables in association with getting a diagnosis of depression from the general practitioner, or being in treatment by a mental health care provider for more than 3 sessions. Causal attributions related to intrapsychic fears were significantly associated with getting a diagnosis of depression and successful referral. Causal attributions related to childhood were also positively associated with successful referral. In association models derived from all the demographic and clinical data available in the survey, causal attributions substantially contributed to the explained variance, 55% and 39% respectively. The findings suggest causal attributions have a statistically significant impact on time to diagnosis and the chance of successful referral. Using the Causal Attribution Inventory with high risk patients in primary care might enhance the chance of detection and successful referral of depressed patients. Schellevis, F. G., Westert, G. P., & De Bakker, D. H. (2005). The actual role of general practice in the dutch health care system. Results of the second dutch national survey of general practice. Medizinische Klinik (Munich), 100(10), 656-661. PMID- 22036104 TI - Normative values of polysomnographic parameters in childhood and adolescence: cardiorespiratory parameters. AB - OBJECTIVE: To provide normative values for pediatric sleep cardiorespiratory parameters following AASM rules, assessing effects of gender, age, and Tanner stage. METHODS: One-night polysomnograhy was performed at subjects' habitual bedtimes in 16 laboratories on 209 healthy German children, 1-18 years old. RESULTS: Normative values of cardiorespiratory parameters in pediatric sleep are presented. No obstructive and mixed apneas occurred. Hypopneas were seldom. Respiratory frequency and apnea-hypopnea-index decreased with age (p<0.001). In all groups central apneas >= 20 s were present but uncommon. Oxygen desaturations or respiratory arousals following central apnea were rare. Heart rate showed an inverse correlation to age (p<0.001). Heart rate was lower in sleep, lowest in stage N. The mean heart rate of females was higher than males (p<0.05). Neither Tanner stage nor corresponding age (p<0.05) influenced: mean apnea duration, central apnea index >= 20 s, hypopnea index, index of periodic breathing, or oxygen saturation nadir. All other parameters except maximal apnea duration and central apnea index after movements with oxygen desaturation show dependency on both Tanner stage and corresponding age (p<0.05). CONCLUSIONS: Using AASM rules, the development of cardiorespiratory parameters in healthy children, ages 1-18 is shown. Age-related norms may improve sleep pathology identification. PMID- 22036105 TI - Prevalence and clinical characteristics of restless legs syndrome in chronic kidney disease patients. AB - OBJECTIVE: To clarify the prevalence of restless legs syndrome (RLS) in the chronic kidney disease (CKD) population and determine the relationship between severity of renal dysfunction and risk of RLS as well as the impact of the disorder on mood and sleep disturbance, we conducted a questionnaire survey followed by face-to-face interviews with Japanese CKD patients. METHODS: We sent a questionnaire battery including demographics items, the National Institutes of Health/International RLS Study Group (IRLSSG) consensus questionnaire, the Center for Epidemiological Studies Depression Scale, and the Pittsburgh Sleep Quality Index to eligible CKD patients (n=514) and age- and sex-matched controls (n=535). Structured interviews were performed for the diagnosis of RLS. RESULTS: The prevalence of positive RLS in the CKD subjects was significantly higher than that in the controls (3.5% vs. 1.5%, p=0.029). The proportion of renal failure (RF) in CKD subjects with RLS was significantly higher than in those without RLS, and multiple logistic regression analysis revealed that the presence of RLS symptoms was associated only with the existence of RF. In addition, the presence of both RLS and CKD was significantly associated with the presence of depression and sleep disturbance. CONCLUSIONS: The risk of RLS in the CKD population was higher than that in the general population and increased with the progression of renal dysfunction. Additionally, the existence of RLS might play a role in an increased risk for developing depression and sleep disturbance in the CKD population. PMID- 22036106 TI - Predictors of adverse outcome in adolescents and adults with isolated left ventricular noncompaction. AB - Isolated left ventricular noncompaction is a rare form of primary cardiomyopathy. Although increasingly diagnosed, data on the outcomes are limited. To define the predictors of adverse outcomes, we performed a retrospective analysis of a prospectively defined cohort of consecutive patients (age >14 years) diagnosed with left ventricular noncompaction at a single center. The baseline characteristics included presentation with a cardiovascular complication (i.e., decompensated heart failure, systemic embolic event, or sustained ventricular arrhythmia). The primary end point was survival free from cardiovascular death or transplantation. The predictors of survival were evaluated using the Kaplan-Meier method and Cox proportional hazards analysis. A total of 115 patients were included, 77% of whom were symptomatic at diagnosis. Compared to the asymptomatic patients, the symptomatic patients were significantly older and had larger left ventricular cavities and worse left ventricular ejection fraction. Of the 115 patients, 49 (43%) presented with a cardiovascular complication. During a median follow-up of 2.7 years (range 0.1 to 19.4), none of the asymptomatic patients died or underwent transplantation compared to 31% (27 of 88) of the symptomatic patients (p = 0.001). The major determinants of cardiovascular death or transplantation were presentation with a cardiovascular complication (hazard ratio 20.6, 95% confidence interval 4.9 to 87.5, p <0.0001) or New York Heart Association class III or greater (hazard ratio 8.8, 95% confidence interval 3.2 to 24.0, p <0.0001). Left ventricular dilation and systolic dysfunction were less strong predictors. In conclusion, in patients with left ventricular noncompaction, New York Heart Association class III or greater and cardiovascular complications at presentation are strong predictors for adverse outcome. PMID- 22036107 TI - Usefulness of immunostaining for plakoglobin as a diagnostic marker of arrhythmogenic right ventricular cardiomyopathy. AB - The clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is often challenging due to phenotypic variation, reduced/age-related penetrance, and lack of a diagnostic test. A single report has suggested quantitative myocardial immunoanalysis for the desmosomal protein plakoglobin as a diagnostic test with high sensitivity and specificity. We performed immunohistochemistry for plakoglobin and a control protein on myocardial biopsies with fibrofatty replacements from 50 consecutive, unrelated patients. The clinical, genetic, and immunohistochemical data were evaluated by independent observers in a blinded manner. The immunohistochemical and clinical diagnoses were compared and the sensitivity, specificity, and predictive values calculated. Our analysis showed 37 samples (74%) with a reduced immunosignal for plakoglobin. Of the 34 patients with a clinical diagnosis of ARVC, 29 displayed a reduced plakoglobin signal. Of the 14 patients with a clinical diagnosis other than ARVC, 6 displayed a reduced signal. Two patients were excluded from further analysis. A sensitivity of 85%, a specificity of 57%, a positive predictive value of 83%, and a negative predictive value of 62% were found. In conclusion, immunohistochemical analysis for plakoglobin, applied as a diagnostic test for ARVC, seems associated with a relatively high sensitivity, but limited specificity, and although additional validation is required, we advocate caution in basing clinical decision-making on the proposed diagnostic test. PMID- 22036108 TI - Effect of statins on creatine kinase levels before and after a marathon run. AB - We measured the serum levels of myoglobin, total creatine kinase (CK), and the CK myocardial (CK-MB), muscle (CK-MM), and brain (CK-BB) isoenzymes in 37 subjects treated with statins and 43 nonstatin-treated controls running the 2011 Boston Marathon. Venous blood samples were obtained the day before (PRE) and within 1 hour (FINISH) and 24 hours after (POST) the race. The hematocrit and hemoglobin values were used to adjust for changes in the plasma volume. The CK distribution was normalized using log transformation before analysis. The exercise-related increase in CK 24 hours after exercise, adjusted for changes in plasma volume, was greater in the statin users (PRE to POST 133 +/- 15 to 1,104 +/- 150 U/L) than in the controls (PRE to POST 125 +/- 12 to 813 +/- 137 U/L; p = 0.03 for comparison). The increase in CK-MB 24 hours after exercise was also greater in the statin users (PRE to POST 1.1 +/- 3.9 to 8.9 +/- 7.0 U/L) than in the controls (PRE to POST 0.0 +/- 0.0 to 4.2 +/- 5.0 U/L; p <0.05 for comparison). However, the increases in muscle myoglobin did not differ at any point between the 2 groups. Increases in CK at both FINISH and POST race measurements were directly related to age in the statin users (r(2) = 0.13 and r(2) = 0.14, respectively; p <0.05) but not in the controls (r(2) = 0.02 and r(2) = 0.00, respectively; p >0.42), suggesting that susceptibility to exercise-induced muscle injury with statins increases with age. In conclusion, our results show that statins increase exercise-related muscle injury. PMID- 22036109 TI - The rich history of neurosurgery at Evanston Hospital. PMID- 22036110 TI - History of Neurosurgery at Evanston Hospital and NorthShore University HealthSystems. PMID- 22036111 TI - Cranial and spinal trauma: current concepts. PMID- 22036112 TI - Malignant gliomas: diagnosis and treatment. PMID- 22036113 TI - Neurosurgical treatment of trigeminal neuralgia. PMID- 22036114 TI - Cervical spondylosis: an update on pathophysiology, clinical manifestation, and management strategies. PMID- 22036115 TI - Surgery for degenerative lumbar spine disease. PMID- 22036116 TI - Pituitary tumors and transsphenoidal surgery. PMID- 22036117 TI - Normal pressure hydrocephalus. PMID- 22036118 TI - Cerebral arteriovenous malformations. PMID- 22036119 TI - Deep brain stimulation for Parkinson's disease, essential tremor, and dystonia. PMID- 22036120 TI - Brain aneurysms: epidemiology, treatment options, and milestones of endovascular treatment evolution. PMID- 22036121 TI - Study of the inhibition of two human maltase-glucoamylases catalytic domains by different alpha-glucosidase inhibitors. AB - In humans, both the N-terminal catalytic domain (NtMGAM) and the C-terminal catalytic domain (CtMGAM) of small intestinal maltase glucoamylase (MGAM) are alpha-glycosidases that catalyze the hydrolysis of alpha-(1->4) glycosidic linkages in the process of starch digestion, and are considered to be the main therapeutic targets for type 2 diabetes. In this work, recombinant human CtMGAM has been cloned for the first time, and this, combined with the expression of NtMGAM in Pichia pastoris, made it possible for us to study the catalytic mechanism of MGAM in a well-defined system. The enzymatic kinetic assays of the two catalytic domains suggest that CtMGAM has the higher affinity for longer maltose oligosaccharides. Kinetic studies of commercially-available drugs such as 1-deoxynojirimycin (DNJ), miglitol, voglibose, and acarbose along with a series of acarviosine-containing oligosaccharides we isolated from Streptomyces coelicoflavus against NtMGAM, CtMGAM, and human pancreatic alpha-amylase (HPA) provide us an overall profile of the inhibitory ability of these inhibitors. Of all the inhibitors used in this paper, DNJ was the most effective inhibitor against MGAM; the K(i) values for the two catalytic domains were 1.41 and 2.04 MUM for NtMGAM and CtMGAM, respectively. Acarviostatins 2-03 and 3-03 were the best inhibitors against HPA with relatively high inhibitory activity against CtMGAM. The acarviostatins 2-03 and 3-03 inhibition constants, K(i), for HPA were 15 and 14.3 nM, and those for CtMGAM were 6.02 and 6.08 MUM, respectively. These results suggest that NtMGAM and CtMGAM differ in their substrate specificities and inhibitor tolerance despite their structural relationship. PMID- 22036122 TI - Interactions of D-cellobiose with p-toluenesulfonic acid in aqueous solution: a (13)C NMR study. AB - The effects of adding D(2)SO(4), and p-toluenesulfonic acid-d to D-cellobiose dissolved in D(2)O were investigated at 23 degrees C by plotting (13)C NMR chemical shift changes (Deltadelta) against the acid to D-cellobiose molar ratio. (13)C Chemical shifts of all 18 carbon signals from alpha and beta anomers of D cellobiose showed gradual decreases due to increasing acidity in aqueous D(2)SO(4) medium. The C-1 of the alpha anomer showed a slightly higher response to increasing D(+) concentration in the surrounding. In the aqueous p toluenesulfonic acid-d medium, C-6' and C-4' carbons of both alpha, and beta anomeric forms of D-cellobiose are significantly affected by increasing the sulfonic acid concentrations, and this may be due to a 1:1 interaction of p toluenesulfonic acid-d with the C-6', C-4' region of the cellobiose molecule. PMID- 22036123 TI - Structural characterization of the O-chain polysaccharide from an environmentally beneficial bacterium Pseudomonas chlororaphis subsp. aureofaciens strain M71. AB - Pseudomonas chlororaphis subsp. aureofaciens strain M71 was isolated from the root of a tomato plant and it was able to control in vivo Fusarium oxysporum f. sp. radicis-lycopersici responsible for the tomato crown and root rot. Recently, strain M71 was evaluated even for its efficacy in controlling Seiridium cardinale, the causal agent of bark canker of common cypress (Cupressus sempervirens L.). Strain M71 ability to persist on the tomato rhizosphere and on the aerial part of cypress plants could be related to the nature of the lipopolysaccharides (LPS) present on the outer membrane and in particular to the O-specific polysaccharide. A neutral O-specific polysaccharide was obtained by mild acid hydrolysis of the lipopolysaccharide from P. chlororaphis subsp. aureofaciens strain M71. By means of compositional analyses and NMR spectroscopy, the chemical repeating unit of the polymer was identified as the following linear trisaccharide. PMID- 22036124 TI - Chronic oral anticoagulant therapy in carotid artery stenting: the un-necessity of perioperative bridging heparin therapy. AB - INTRODUCTION: Chronic oral anticoagulant therapy (OAT) is of widespread use, and usually its management in patients undergoing carotid artery stenting (CAS) is through perioperative bridging heparin therapy. Aim of the present study is to analyze a single center experience of CAS in patients maintaining OAT without perioperative bridging heparin therapy. MATERIALS AND METHODS: A retrospective evaluation of consecutive patients submitted to CAS was performed. Clinical anatomical characteristics and chronic OAT were evaluated to find a correlation with stroke, death, myocardial infarction and bleeding from the access site by Chi-square, Fisher's tests and regression analysis. RESULTS: 502 CAS were performed in a 5-year period. Twelve (2.4%) strokes, 1 (0.2%) death, no myocardial infarctions and 4 (0.8%) access site bleeding occurred in the perioperative period. In the overall population the presence of type 3 or bovine aortic arch was associated with stroke (5.5% vs. 1.5% p=0.02), and preoperative neurological ischemic symptoms were correlated with higher incidence of the composite event of stroke/death (4.8% vs. 1.4%, p=0.05). Twenty patients (4.0%) under chronic OAT were submitted to CAS without perioperative bridging heparin therapy with no complications. Overall, patients under OAT had no significantly different outcome compared with patients without OAT. CONCLUSIONS: OAT without perioperative bridging heparin therapy is safe and effective. This data could be useful in the management of patients with chronic OAT submitted to CAS. PMID- 22036125 TI - The impact of platelet membrane glycoprotein Ib alpha and Ia/IIa polymorphisms on the risk of thrombosis in the antiphospholipid syndrome. AB - BACKGROUND: Pathogenesis of thrombus formation in antiphospholipid syndrome (APS) is not clear. Platelet membrane glycoprotein (GP) receptors play important roles in development of thrombosis. OBJECTIVES: We investigated the association between development of thrombosis in APS and polymorphisms of GPIb alpha variable number of tandem repeats (VNTR), Kozak, and GPIa C807T. Patients/Methods Sixty patients with APS (30 with proven thrombosis and 30 without thrombosis) and 63 controls were included. Presence of GPIa C807T polymorphism was determined with real-time PCR and GPIb alpha Kozak and VNTR polymorphisms by conventional PCR. RESULTS: Frequency of C807T TT genotype was significantly higher in APS with thrombosis than APS without thrombosis (p=0.023) and also in APS with multiple thrombi compared to APS without thrombi (p=0.023). Frequency of Kozak TC genotype was higher in APS with arterial thrombosis compared to APS with venous thrombosis, controls, and APS without thrombosis (p=0.03, p=0.0007, and p=0.0024 respectively). D allele frequency and D allele carrier state for VNTR were significantly less in APS than controls (p=0.0018 and p=0.0046 respectively). CONCLUSIONS: C807T TT genotype may confer a risk for thrombosis and Kozak TC genotype for arterial thrombosis. D allele of VNTR may protect from APS. No patients with C807T TT or Kozak TC genotypes carried the protective DD genotype of VNTR. These polymorphisms may increase risk for both arterial and venous thrombosis. The utility of prophylaxis with anti-platelet drugs in at least a subgroup of APS patients should be investigated with clinical trials. PMID- 22036126 TI - Reproducibility of echocardiographic diagnosis of left ventricular noncompaction. AB - BACKGROUND: Left ventricular noncompaction (LVNC) cardiomyopathy is variably defined by numerous trabeculations, deep intertrabecular recesses, and noncompacted-to-compacted (NC/C) ratio >2. Limited studies exist on the reproducibility of diagnosing LVNC. METHODS: Clinical records of patients diagnosed with LVNC by echocardiography were reviewed. Blinded review of the index echocardiogram for all patients and a 1:1 match without LVNC was performed independently by two observers, measuring the number of trabeculations and the NC/C ratio. RESULTS: A total of 104 patients with LVNC were included in the study, 52 with no congenital heart disease (NCongHD) and 52 with congenital heart disease (CongHD). The duration of follow-up was 7.2 years (range, 0.5-23.1 years) for NCongHD and 8.2 years (range, 0-33.3 years) for CongHD. Agreement between observers in determining zero to three versus more than three trabeculations was 59% (NCongHD) and 73% (CongHD). Agreement in measuring an NC/C ratio <= 2 versus > 2 was 79% (NCongHD) and 74% (CongHD). Agreement with the original reader in diagnosing LVNC was 67%. There was no association between the number of trabeculations or the NC/C ratio and the likelihood of a major event. Patients with moderate or severe left ventricular dysfunction at the time of diagnosis were more likely to undergo cardiac transplantation or die compared with those with normal or mild dysfunction (NCongHD, 22% vs 0%, P = .01; CongHD, 39% vs 3%, P = .001). CONCLUSIONS: The reproducibility of making measurements to diagnose LVNC by accepted criteria is poor. Heart transplantation and death are associated with significant ventricular dysfunction and not with increased trabeculations or NC/C ratios. PMID- 22036127 TI - Impact of preoperative anterior leaflet tethering on the recurrence of ischemic mitral regurgitation and the lack of left ventricular reverse remodeling after restrictive annuloplasty. AB - BACKGROUND: The aim of this multicenter study was to investigate the impact of the preoperative anterior mitral leaflet tethering angle, alpha', on the recurrence of mitral regurgitation (MR) and left ventricular (LV) reverse remodeling (LVRR) after undersized mitral ring annuloplasty. METHODS: The study population consisted of 362 patients, who were divided into two groups by baseline alpha': group 1, alpha' < 39.5 degrees (n = 196), and group 2, alpha' >= 39.5 degrees (n = 166). End points were recurrent MR >= 2+; LVRR, defined as a reduction in end-systolic volume index > 15%; and LV geometric reverse remodeling, defined as a reduction in systolic sphericity index to a normal value of <0.72 in patients with altered baseline geometry. RESULTS: MR occurred in 9.6% (n = 19) and 43.3% (n = 72) of the patients in groups 1 and 2, respectively (P < .001). LVRR (85.7% vs 22.2%) at follow-up was higher in group 1 (P < .001). On multivariate regression analysis, alpha' >= 39.5 degrees was a strong predictor of MR recurrence, lack of LV reverse remodeling and lack of LV geometric reverse remodeling (all P values < .001). In contrast, the posterior mitral leaflet tethering angle, beta', was not significant (all P values > .05). When we allowed for interactions between alpha' and other risk factors, this effect occurred also in low-risk subgroups, and it was equivalent or generally attenuated in higher risk patients. There were no significant interactions between alpha' and any of the covariates (all P values > .05). CONCLUSIONS: Anterior mitral leaflet tethering is a powerful predictor of MR recurrence and lack of LVRR after undersized mitral ring annuloplasty. Evaluation of leaflet tethering should be incorporated into clinical risk assessment and prediction models. PMID- 22036128 TI - Enhancing the clinical pathway for patients undergoing axillary lymph node dissection. AB - BACKGROUND: Day-case axillary lymph node dissection (ALND) is not standard practice. Here we assess the feasibility of converting this traditional inpatient procedure to an outpatient procedure without compromising the quality or continuity of patient care, identify barriers to introducing an enhanced clinical pathway based on this conversion, and report strategies employed to overcome these barriers. METHODS: Consecutive patients (n=282) undergoing ALND alone or with a concurrent breast procedure (excluding mastectomy/reconstruction) over a 12-month period were recorded in a prospective database. Assessed outcomes were successful discharge the day of surgery, early postoperative complication rates, and readmission rates. RESULTS: From July 2009 to June 2010, 282 ALNDs were performed at Memorial Sloan-Kettering Cancer Center. 240 (85.1%) were performed as an outpatient procedure and 42 (14.9%) had inpatient ALND. The readmission rate was 0.8% (2/240), and the reoperation rate was 0.7% (2/282). Outpatient ALND procedure implementation created 240 additional beds over the 12-month study period. Identified barriers to implementing this new clinical pathway included patient expectations, reducing narcotic administration while optimizing postoperative pain control, and facilitating preoperative patient education. CONCLUSION: ALND may be safely performed as a day-case procedure. The key to successfully implementing ALND as a day-case procedure is a multidisciplinary team approach combined with enhanced pre and postoperative patient education. In addition, changes in the mindsets of patients and health care providers are essential. PMID- 22036129 TI - Anticancer drug use in geriatric patients: concerns and challenges. PMID- 22036130 TI - National versus international generalizations from cost-effectiveness analyses. PMID- 22036131 TI - Predictors of distal radioulnar joint instability in distal radius fractures. AB - PURPOSE: A tear of the triangular fibrocartilage complex (TFCC) is the most frequent soft tissue injury associated with fractures of the distal radius, and repair of the deep ligamentous portion of the TFCC is considered when the tear contributes to instability of the distal radioulnar joint (DRUJ). The purpose of this prospective cohort study was to identify predictors of DRUJ instability accompanying unstable distal radius fractures. METHODS: Between 2002 and 2007, we prospectively treated 163 consecutive patients with unstable distal radius fractures with the volar locking plating system. Complete radioulnar ligament tears representing DRUJ instability were present in 11 of 163 distal radius fractures. We tested univariate associations between DRUJ instability and potential predictors and conducted multivariate analysis to establish independent predictors of instability. We applied receiver operating characteristics curves within the significant risk factors to determine threshold values. RESULTS: In univariate analyses, only the radial and sagittal translation ratios of the fracture site were significant predictors of DRUJ instability. Multivariate logistic regression analysis confirmed that the radial translation ratio, which corresponds to a normalized DRUJ gap, was a significant risk factor. According to the receiver operating characteristics curve for the radial translation ratio, the area under the curve was 0.89. A cutoff value of 15% for the radial translation ratio showed the highest diagnostic accuracy rate. CONCLUSIONS: A radiographic finding of a normalized DRUJ gap on posteroanterior views was the most important predictor to identify DRUJ instability accompanying unstable distal radius fractures. The relative risk of instability increases by 50% when the ratio of DRUJ widening increases by 1%. PMID- 22036132 TI - Towards a higher impact factor for the Journal of the Chinese Medical Association. PMID- 22036134 TI - Chromobacterium violaceum infection: a clinical review of an important but neglected infection. AB - BACKGROUND: Increasing reported cases with Chrombacterium violaceum infection has been noticed in recent decades. It is noteworthy for its difficult-to-treat entity characterized by a high frequency of sepsis, easily distantant metastasis, multidrug-resistance, and frequent relapse, and high mortality rate. METHODS: The English-language literature was reviewed from 1952 through December 2009 by an electronic view via the PubMed and Medline databases and manual searches. RESULTS: One hundred and six patients with Chrombacterium violaceum infection from the literature were studied. The four leading clinical manifestations reviewed in the published literature, in the order of frequency, were fever (100%), sepsis (82%), skin lesions (67.9%), and abdominal pain (31.1%). Localized abscess was found in 52 patients (49%) and liver was the mostly common involved organ. Fifty-six patients (53%) were dead. Almost all of the penicillin, ampicillin, and first and second-generation cephalosporins exhibited totally resistant to Chrombacterium violaceum. The most important risk factors in mortality in 61 patients with Chrombacterium violaceum bacteremia were at a young age (p = 0.0789), presence of localized abscess (p = 0.030), shorter clinical course (p < 0.001), and inappropriate antimicrobial treatment (p < 0.001). Seven patients (6.6%) experienced of relapse or reinfection, with a median interval of 135 days (range, 4 to 1095 days). CONCLUSIONS: A high index of suspicion for Chromobacterium violaceum infection is required along with prompt diagnosis, optimal antimicrobial therapy, and adequate therapeutic duration for a successful therapy. PMID- 22036133 TI - Are we satisfied with the tools for the diagnosis of gonococcal infection in females? AB - Gonorrhea (Neisseria gonorrhoeae) is a common sexually transmitted infection in women, with a heavy burden on female and neonatal health, because sequelae occur, such as female infertility, ectopic pregnancy, neonatal ophthalmitis and infection, and chronic pelvic pain. Prompt and appropriate antibiotic treatment can cure infection and avoid complications. However, adequate treatment is not easy, because early and rapid identification of gonorrhea is interfered with by many factors, including the complicated mixed microflora of the vagina and cervix, non-user-friendly culture systems, and lack of immediate availability of results, even with a combination of subjective complaint and high clinical suspicion. A PubMed search was conducted using the major headings of "gonorrhoea and diagnostic tool" and "Neisseria gonorrhoeae and diagnostic tool", before the end of 2010. Recently available methods for the diagnosis of gonorrhea infection in women were included, including traditional tools and advanced technology. Traditional tools such as microscopic examination and microbial culture have been used broadly; unfortunately, they have relatively lower specificity or sensitivity, and most importantly, "see-and-treat" is impossible for these infected women. Advances in technology, such as antigen detection by immunoassay and nucleic acid amplification tests (NAATs), have achieved major progress in the diagnosis of gonorrhea, because of their accuracy, convenience and time-saving aspects. However, NAATs are expensive, making their acceptance impossible in developing countries. Detection of pathogens including N. gonorrheae using microarray chips is viewed as a possible solution, because it is a relatively rapid, easy, inexpensive and sensitive tool, which makes an "identify-and-treat" or point-of-care policy possible. A rapid and affordable tool with high sensitivity and specificity for detection of gonorrhea in developing countries is still not available at the time of writing. To make a point-of-care policy possible, advanced technology for aiding diagnosis of gonorrhea is encouraged and appreciated. PMID- 22036136 TI - Effects of fluid resuscitation on cerebral tissue oxygenation changes in a piglet model of hemorrhagic shock. AB - BACKGROUND: Acute blood loss linked to severe hypovolemia and hemorrhagic shock is a critical condition in pediatric intensive care. This study was to investigate the role of various fluid resuscitation approaches to cerebral tissue oxygenation using a piglet model of hemorrhagic shock. METHODS: Thirty piglets received blood removal to induce hemorrhagic shock, and then were randomly assigned to a control group (no treatment), a control-normal saline (NS) group (treated with bolus normal saline 10 mL/kg only), or one of three treatment groups treated with 15 mL/kg/dose fluid every 30 min with either whole blood (WB), lactated Ringer's solution (LR), or NS in addition to an initial bolus of saline. The piglets' physiological profiles, arterial blood gases, and regional cerebral oxygen saturation (rScO(2)) levels were recorded, fractional tissue oxygen extraction was calculated, and blood hemoglobin levels were measured. RESULTS: The results showed that no matter whether treated with only one dose of bolus NS (control-NS group) or with extra WB, LR, or NS, all the treated animals had a significantly higher survival rate, mean arterial blood pressure (MAP), arterial oxygen tension, arterial oxygen saturation, and rScO(2) than the control group (p<0.05). Animals treated with WB all survived the full experimental period, and their hemoglobin levels, MAP, and rScO(2) were the highest comparing to all other groups (p<0.05). CONCLUSION: Effective resuscitation using a high concentration of inspired oxygen and adequate fluid infusion, either as a single dose bolus of NS or combining this with a subsequent transfusion of WB, LR, or NS, helped to stabilize the cardiovascular condition of the tested young subjects and improved cerebral tissue oxygenation over the emergent first four hours. Furthermore, WB was the best fluid choice when used in addition to the bolus NS challenge for maintaining better brain tissue oxygenation when treating hemorrhagic shock. PMID- 22036135 TI - Clinical and biochemical indicators of homeostasis model assessment-estimated insulin resistance in postmenopausal women. AB - BACKGROUND: Homeostasis model assessment of insulin resistance (HOMA-IR) is a surrogate estimate of directly measured insulin resistance that been robustly proven to be associated with diabetes and cardiovascular disease. The purpose of this study was to evaluate the use of several simple indicators to identify postmenopausal women with insulin resistance estimated by HOMA-IR. METHODS: We recruited 262 naturally postmenopausal women without overt diabetes for the study. HOMA-IR values were calculated from fasting glucose and insulin levels. Multiple linear regression analyses were carried out to detect determinants of HOMA-IR. Insulin resistance was conventionally defined as the upper quartile of the HOMA-IR values. The diagnostic power of clinical and biochemical markers for insulin resistance was assessed using receiver operating characteristic curves. RESULTS: Some 90% of the women with HOMA-IR >= 2.8 (75th percentile as cutoff) showed abnormal glucose metabolism and 45% of them had silent diabetes (odds ratio 6.09, 95% CI 3.17 - 11.73 vs. those with HOMA-IR < 2.8). Results revealed that uric acid, body mass index, waist circumference, alanine aminotransferase, triglycerides, and high-density lipoprotein cholesterol were important determinants of HOMA-IR in these women. Using uric acid >= 5.0 mg/dL as a cutoff point, we could diagnose insulin resistance with 75.4% sensitivity and 73.1% specificity. CONCLUSION: Postmenopausal women with HOMA-IR-estimated insulin resistance were at high risk of glucose abnormalities in this study. High HOMA-IR values were significantly associated with six clinical and biochemical indicators. Among these, high serum uric acid levels seemed to be a useful marker identifying postmenopausal women with insulin resistance. This study was registered at clinicaltrials.gov as NCT00945271. PMID- 22036137 TI - Are patients with the symptoms of overactive bladder and urodynamic detrusor overactivity different from those with overactive bladder but not detrusor overactivity? AB - BACKGROUND: The aim of this study is to identify the differences between patients with overactive bladder (OAB) and detrusor overactivity (DO) and those with OAB but without DO. METHODS: We prospectively recruited patients with OAB symptoms between December 2008 and September 2009. All patients were required to complete a 3-day frequency-volume chart. Symptom severity was evaluated using the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) questionnaires. All patients also underwent urodynamic studies. Demographics, symptom severity, urinary frequency and volume, and urodynamic variables of patients with and without DO were compared. RESULTS: Of the 133 enrolled patients (76 women and 57 men), DO was diagnosed in 80 patients (60.2%). All demographic variables were similar among the OAB patients, regardless of DO status. Total IPSS and OABSS scores did not differ between the OAB and DO groups. However, the nighttime urinary frequency subscore on the OABSS differed significantly between OAB patients with DO and without DO (p = 0.048). There were no significant differences in terms of urodynamic variables, urinary frequency, or urine volume between OAB patients with and without DO. CONCLUSION: Patients with OAB symptoms and urodynamic DO show different clinical symptoms than OAB patients without DO. Patients with DO experience more frequent nocturnal urinary episodes. PMID- 22036138 TI - Metallic stent in the treatment of ureteral obstruction: experience of single institute. AB - BACKGROUND: The Resonance((r)) metallic stent has been reported to be sufficient for the management of malignant extrinsic ureteral obstructions within a 12-month time period. To determine the effectiveness in each specific patient group, we report our experience using the Resonance((r)) stent in the treatment of ureteral obstructions. METHODS: We retrospectively reviewed 20 patients (23 stents) who successfully received the Resonance((r)) metallic stents and divided them into a patent group (n = 19) and an obstructive group (n = 4) according to the treatment results. Twenty-one stents were inserted via cystoscopy or ureteroscopy in a retrograde fashion. The remaining two were inserted via percutaneous nephrostomy in an antegrade manner. Follow-up serum creatinine measurements and sonography were performed. The overall ureteral patency rate and the risk of stent failure were evaluated. RESULTS: The overall ureteral patency rate was 82.6% (19/23). Patients with previous radiotherapy had a 50% (4/8) patency rate which was significantly lower than non-radiotherapy patients (100%, 15/15, p = 0.028). Malignant obstructions in those other than radiotherapy patients had a 100% patency rate (5/5). Benign obstructions in those other than radiotherapy patients had a 100% patency rate (10/10). In the radiotherapy patients, the mode of therapy did not dominate the stent outcome. CONCLUSION: Patients with ureteral obstructions can be treated sufficiently with the Resonance((r)) metallic stent. Patients who had gynecological malignancies and received radiotherapy had a higher failure rate after Resonance((r)) metallic stent insertion. PMID- 22036139 TI - Diagnostic pitfalls of nonsecretory myeloma manifesting as multiple foci of periosseous plasmacytomas. AB - Nonsecretory myeloma, which comprises 1-5% of all myelomas, is a variant of plasma cell myeloma. It is defined as symptomatic myeloma without detectable monoclonal immunoglobulin levels on serum or urine immunofixation electrophoresis. Here, we report two cases of nonsecretory plasma cell myeloma that manifested as multi-foci periosseous plasmacytomas. Due to the inability to detect monoclonal immunoglobulin on serum or urine immunofixation electrophoresis and the lack of evidence of clonal plasma cells in the bone marrow, it was difficult to establish an early, accurate diagnosis. Misdiagnosing or mislabeling symptomatic myeloma patients with plasmacytoma results in the delay of their systemic treatment. Therefore, comprehensive imaging studies, the detection of free light chains, and histopathological confirmation from different sites and time points are necessary. PMID- 22036140 TI - Melorheostosis of the ulna. AB - Melorheostosis is a rare osteosclerotic bone dysplasia. It is usually characterized by dull and aching pain, reduced joint motion and contractures. Classic radiograph findings are of undulating cortical hyperostosis along the length of the bone, simulating a "dripping candlewax appearance". We report two cases of melorheostosis of the ulna bone, diagnosed 6 years apart in two different females in their early 20s. Both the patients presented with the characteristic features of dull and aching pain in the forearm and were treated conservatively. However, we misdiagnosed the first case as bone malignancy and subjected the patient to a biopsy. For the second case, with hindsight we made the correct diagnosis based only on the classic clinical history and radiographs. We believe that the discussion of a misdiagnosed case of melorheostosis with salient findings may be important for clinicians and orthopedicians in day-to-day clinical practice. PMID- 22036141 TI - Combination photodynamic therapy and intravitreal bevacizumab used to treat circumscribed choroidal hemangioma. AB - Circumscribed choroidal hemagioma (CCH) is an ocular tumor that can result in decreased vision or blindness. Numerous treatment methods have been reported without satisfying results. In recent years, photodynamic therapy (PDT) with verteporfin has been used to treat choroidal hemagioma and resolve the associated exudative retinal detachment, and the results have been inspiring. Here, we report the case of a 36-year-old man with longstanding CCH who suffered from blurred vision for 3 years. He underwent PDT with intravenous infusions of verteporfin, which was a treatment method based on a modified version of the standard macular degeneration PDT protocol, in addition to subsequent intravitreal administrations of bevacizumab as adjuvant therapy for macular edema. Twelve months after treatment, the CCH tumor remained noticeably shrunken, with the complete absorption of the subretinal fluid and the absence of macular edema. In terms of treating subretinal fluid retention, this combination treatment is a safe, effective, and long-lasting therapy for treating established CCH tumors. However, even though the patient's visual field defects improved, the patient's visual acuity remained stable at 6/60 without further improvement. Long term CCH with prolonged macular edema might have affected the visual prognosis. Patients with CCH still require long-term follow-up examinations after receiving PDT treatments. PMID- 22036142 TI - Transitional cell carcinoma of the ovary. PMID- 22036144 TI - [Incontinentia pigmenti. Four patients with different clinical manifestations]. AB - Incontinentia pigmenti (IP) is a rare neurocutaneous disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in IKBKG gene (NEMO) in Xq28, inherited as an X-linked dominant trait. Clinical manifestations detected since the newborn period are highly variable, with 3 well established sequential or overlapped states and each with a characteristic differential diagnosis. With PCR+RFLPs, we analyzed the IKBKG gene in 4 patients with different clinical manifestations and characteristic skin biopsy. In all 4 patients the same deletion of exons 4 to 10 was identified. In female patients in whom the dermatological lesions lead to the suspicion of an IP diagnosis, it is important to have the complete, multidisciplinary and molecular analysis of their first level female relatives. This should give us a clear diagnosis, which is the first step to complete genetic counselling. PMID- 22036145 TI - [Abdominal rhabdomyosarcoma presenting as a unilateral pleural effusion]. PMID- 22036146 TI - Allograft cellular bone matrix as an alternative to autograft in hindfoot and ankle fusion procedures. AB - This report summarizes the radiographic results of Osteocel Plus in 20 hindfoot and ankle fusions at a single center. The patient population was 40% female with an average age of 57.9 +/- 16.1 years. Average body mass index was 33.8 +/- 9.1. Risk factors included 3 smokers and 6 patients with diabetes. Primary surgical indications included trauma (50%), Charcot arthropathy (15%), foot drop with osteoarthritis (20%), primary osteoarthritis (10%), and total talar extrusion (5%). Nine patients had a history of prior hindfoot surgery in the same foot; however, only 2 of the cases reported in this series were revisions due to a failed prior surgery; the remaining 7 were treated for correction of a traumatic deformity (n = 5) or diagnosis at a new site in the same foot (n = 2). Treatment included subtalar joint arthrodesis (50%), ankle arthrodesis (40%), triple fusion (5%), and tibial-calcaneal-calcaneal-cuboid arthrodesis (5%). Solid fusion was observed in 100% of patients by the 6-month evaluation. Average time to fusion was 13.5 weeks. Although patients with a prior surgery trended toward a longer time to fusion than patients who underwent their first hindfoot and ankle procedure (14.4 +/- 5.3 vs. 12.6 +/- 5.7 weeks), the difference was not statistically significant (p = .47). There was no evidence of graft rejection or failure. This series demonstrates that mesenchymal stem cell-based bone allograft is a safe and effective bone-healing material with a high radiographic success rate in foot and ankle arthrodeses with successful and timely fusion rates. PMID- 22036147 TI - Incorporation of bovine-based structural bone grafts used in reconstructive foot surgery. AB - Timely incorporation of bone grafts is essential to the structural rigidity in most foot and ankle surgeries. Although bovine-based xenografts possess some of the key features necessary for foot and ankle surgery, the studies evaluating the efficacy of these grafts are limited. The aim of the present study was to determine the incorporation rate of bovine-based bone grafts in foot surgery. A total of 22 patients who had undergone reconstructive foot surgery using 31 bovine-based xenografts were identified, and the rate of radiographic incorporation of the grafts was evaluated. A survival analysis was used to show the trend of the incorporation of the xenografts over time. Of the 21 grafts observed for at least 12 weeks, none showed radiographic graft incorporation by 12 weeks. The analogous numbers for 24, 36, and 48 weeks were 3 (20%) of 15, 4 (31%) of 13, and 3 (27%) of 11 grafts. A total of 19 (61.29%) of the 31 grafts studied were never observed to have incorporated radiographically, for the entire observation period. A Kaplan-Meier estimate revealed the median interval to graft incorporation was 56 weeks. Compared with previous studies, which investigated the incorporation of other types of grafts, such as autograft and allografts, we believe that xenografts incorporate more slowly. For this reason, such grafts might not be ideal for use in reconstructive foot surgery. PMID- 22036148 TI - A study of the dynamics of digital dermatitis in 742 lactating dairy cows. AB - Digital dermatitis (DD) is a contagious disease of cattle affecting the skin of the claw. The disease presents with a range of severities and can be associated with lameness. Information about the disease dynamics of DD is scarce. Parity and lactation stage have been identified as risk factors for DD and studies have also indicated that not all cows are equal regarding their risk of recurrent disease and prospects for cure from DD. The aim of this study was to investigate host heterogeneity to DD and to identify disease patterns of DD and factors associated with the development and resolution of lesions. In three commercial dairy herds, 742 lactating cows were observed for DD lesions weekly for 11 or 12 weeks. The effects of parity, lactation stage and duration of preceding episode on the hazard of transitions between healthy and lesion states were analysed using a multilevel multistate discrete-time model. One or more DD lesions were observed in 460 cows and lesions were observed in 2426 out of 10,585 observations. In total, 1755 uncensored episodes with DD lesions were observed. Early lactation was associated with a reduced risk of developing lesions compared with mid and late lactation. Lesions that developed in late lactation had a greater likelihood of resolution compared with lesions that developed during early lactation. There was a reduced risk of lesions developing in parity 3 compared with parity 1 cows, but an increased risk of lesions developing in parity 2 compared with parity 1 cows. In the present study, the mean duration of uncensored DD episodes was 1.7 weeks indicating that the duration of the majority of DD lesions might be shorter than the 42 days reported previously. The transitions between disease states suggest that DD is a dynamic disease, and that the early stage lesions are more transient than expected from previous studies. We conclude that studies with shorter observation intervals than one week are needed to fully understand and describe the individual and group dynamics of DD. PMID- 22036149 TI - [Surgical anatomy of the lateral ventricles]. AB - The lateral ventricle is a deep-seated cavity, overlayed by a cortical mantle which contains eloquent areas, especially on the dominant hemisphere, and surrounded by the optic radiations. The surgical approach requires a thorough preoperative reflexion based on magnetic resonance imaging, in order to understand the site of origin and the vascular pedicles of the tumor. Surgical approaches to the frontal horn, temporal horn and atrium are successively described. PMID- 22036150 TI - Photofunctional multilayer films by assembling naked silver nanoparticles and a tailored nitric oxide photodispenser at water/air interface. AB - This contribution reports the design, preparation, and characterization of nanostructured hybrid films of silver nanoparticles (AgNPs) and a tailored nitric oxide (NO) photodonor. They were achieved by exploiting effective interfacial interactions between an amino-terminated NO photodonor spread onto water surface and naked AgNPs dissolved in the water subphase. The morphology, the spectroscopic features, and the interaction between the two components in the floating films at the air/water interface were inspected by Brewster Angle Microscopy, UV-Vis reflection, and polarization-modulation infrared reflection absorption spectroscopy. AgNPs and the NO photodonor were successfully transferred onto hydrophobized quartz substrates by horizontal lifting deposition and the resulting multilayer films were characterized by UV-Vis absorption spectroscopy and transmission electron microscopy, respectively. The results obtained showed the presence of both isolated AgNPs and assemblies of AgNPs having nanodimensional character in the films. The photochemical properties of the NO photodonor were well preserved in the hybrid multilayers. In fact, they were able to release NO under visible light excitation, as unambiguously demonstrated by the direct and in real-time monitoring of this transient species using an ultrasensitive electrode, and the transfer of the released NO to a protein such as myoglobin. PMID- 22036151 TI - Intake of 238U and 232Th through the consumption of foodstuffs by tribal populations practicing slash and burn agriculture in an extremely high rainfall area. AB - The concentration of naturally occurring radionuclides 232Th, 238U was determined using Instrumental Neutron Activation Analysis (INAA) in different food groups namely cereals, vegetables, leafy vegetables, roots and tubers cultivated and consumed by tribal population residing around the proposed uranium mine. The study area is a part of rural area K. P. Mawthabah (Domiasiat) in the west Khasi Hills District of Meghalaya, India located in the tropical region of high rainfall that remains steeped in tribal tradition without much outside influence. Agriculture by Jhum (slash and burn) cultivation and animal husbandry are the main occupation of the tribal populations. A total of 89 samples from locally grown food products were analyzed. The concentration of 238U and 232Th in the soil of the study area was found to vary 1.6-15.5 and 2.0-5.0 times respectively to the average mean value observed in India. The estimated daily dietary intake of 238U and 232Th were 2.0 MUg d-1 (25 mBq d-1) and 3.4 MUg d-1 (14 mBq d-1) is comparable with reported range 0.5-5.0 MUg d-1 and 0.15-3.5 MUg d-1 respectively for the Asian population. PMID- 22036152 TI - The simulation of long-range transport of 137Cs from East Asia to Japan in 2002 and 2006. AB - To evaluate the quantities of 137Cs from past nuclear tests being transported to and deposited in Japan by naturally-occurring phenomena, the authors developed long-range transport models for 137Cs considering Asian dust. The simulation using these models backed the observed recent increase of 137Cs deposition along the coast of the Sea of Japan in early spring. For the sake of public safety, it is vital to ascertain whether an increase of radioactive deposition is caused by natural phenomena or a nuclear accident. The observations in recent years have suggested that dust and soil containing 137Cs is transported from the regions around Inner Mongolia to Japan by the wind. In this paper, using observation data from the early spring of 2002 and 2006, the authors have found good agreement between the simulations and the measurements. The simulations reproduced the entrainment of 137Cs and subsequent transport to Japan caused by strong winds associated with low pressure areas around the Inner Mongolian grasslands. The most likely cause of high-level 137Cs deposition over northern Japan during March 2002 was 137Cs associated with particles transported at low-altitude (1 km) and subjected to precipitation on the 22nd to 24th. PMID- 22036153 TI - Derivation of hazardous doses for amphibians acutely exposed to ionising radiation. AB - Derivation of effect benchmark values for each taxonomic group, which has been difficult due to lack of experimental effects data, is required for more adequate protection of the environment from ionising radiation. Estimation of effects doses from nuclear DNA mass and subsequent species sensitivity distribution (SSD) analysis were proposed as a method for such a derivation in acute irradiation situations for assumed nuclear accident scenarios. As a case study, 5% hazardous doses (HD5s), at which only 5% of species are acutely affected at 50% or higher lethality, were estimated on a global scale. After nuclear DNA mass data were obtained from a database, 50% lethal doses (LD50s) for 4.8 and 36% of the global Anura and Caudata species, respectively, were estimated by correlative equations between nuclear DNA mass and LD50s. Differences between estimated and experimental LD50s were within a factor of three. The HD5s obtained by the SSD analysis of these estimated LD50s data were 5.0 and 3.1 Gy for Anura and Caudata, respectively. This approach was also applied to the derivation of regional HD5s. The respective HD5s were 6.5 and 3.2 Gy for Anura and Caudata inhabiting Japan. This HD5 value for the Japanese Anura was significantly higher than the global value, while Caudata had no significant difference in global and Japanese HD5s. These results suggest that this approach is also useful for derivation of regional benchmark values, some of which are likely different from the global values. PMID- 22036154 TI - Impact of water quality parameters on the sorption of U(VI) onto hematite. AB - In this study, the sorption of U(VI) from aqueous solution on hematite was studied as a function of various water quality parameters such as contact time, pH, ionic strength, soil humic acid (HA) or fulvic acid (FA), solid content and temperature by using a batch technique. The results demonstrated that the sorption of U(VI) was strongly dependent on ionic strength at pH<6.0, and outer sphere surface complexation may be the main sorption mechanism. The sorption was independent of ionic strength at pH>6.0 and the sorption was mainly dominated by inner-sphere surface complexation. The presence of HA/FA increases U(VI) sorption at low pH, whereas decreases U(VI) sorption at high pH. The thermodynamic parameters (DeltaH0, DeltaS0, and DeltaG0) were calculated from the temperature dependent sorption isotherms, and the results suggested that U(VI) sorption was a spontaneous and endothermic process. The results might be important for the application of hematite in U(VI) pollution management. PMID- 22036155 TI - Mapping of cosmic radiation dose in Croatia. AB - The Earth is continually bombarded by high-energy particles coming from the outer space and the sun. These particles, termed cosmic radiation, interact with nuclei of atmospheric constituents and decrease in intensity with depth in the atmosphere. Measurements of photon and gamma radiation, performed with a Radiameter at 1 m above the ground, indicated dose rates of 50-100 nSv/h. The neutron dose rate was measured with the CR-39 track etch detector calibrated by the CERN-EU high-energy Reference Field (CERF) facility. Correlation between neutron dose rates and altitudes at 36 sites was examined in order to obtain a significant positive correlation coefficient; the resulting linear regression enabled estimation of a neutron dose at particular altitude. The measured neutron dose rate in Osijek (altitude of 89 m, latitude of 45.31 degrees N) was 110 nSv/h. PMID- 22036156 TI - HTO and OBT activity concentrations in soil at the historical atmospheric HT release site (Chalk River Laboratories). AB - Tritium is routinely released by the Chalk River Laboratories (CRL) nuclear facilities. Three International HT release experiments have been conducted at the CRL site in the past. The site has not been disturbed since the last historical atmospheric testing in 1994 and presents an opportunity to assess the retention of tritium in soil. This study is devoted to the measurement of HTO and OBT activity concentration profiles in the subsurface 25 cm of soil. In terms of soil HTO, there is no evidence from the past HT release experiments that HTO was retained. The HTO activity concentration in the soil pore water appears similar to concentrations found in background areas in Ontario. In contrast, OBT activity concentrations in soil at the same site were significantly higher than HTO activity concentrations in soil. Elevated OBT appears to reside in the top layer of the soil (0-5 cm). In addition, OBT activity concentrations in the top soil layer did not fluctuate much with season, again, quite in contrast with soil HTO. This result suggests that OBT activity concentrations retained the signature of the historical tritium releases. PMID- 22036157 TI - Short- and long-term patterns of 137Cs in fish and other aquatic organisms of small forest lakes in southern Finland since the Chernobyl accident. AB - We summarize the patterns of 137Cs activity concentrations and transfer into fish and other biota in four small forest lakes in southern Finland during a twenty year period following the Chernobyl accident in April 1986. The results from summer 1986 showed fastest accumulation of 137Cs into planktivorous fishes, i.e. along the shortest food chains. Since 1987, the highest annual mean values of 137Cs have been recorded in fish occupying the highest trophic levels, for perch (Perca fluviatilis) 13,600 Bq/kg (ww) and for pike (Esox lucius) 20,700 Bq/kg (ww). At the same time, activity concentrations of 137Cs in crustacean zooplankton and Asellus aquaticus have ranged between 1000 and 19,500 Bq/kg (dw). In 2006, 5-28% of the 1987 137Cs activity concentration levels were still present in perch and pike. Since 1989 their 137Cs activity concentrations in oligohumic seepage lakes have remained significantly higher than in polyhumic drainage lakes due to the increased transfer of 137Cs into fish in the seepage lakes with lower electrolyte concentrations, longer water retention times and lower sedimentation rate. PMID- 22036158 TI - Natural radioactivity levels in topsoil from the Pearl River Delta Zone, Guangdong, China. AB - Concentrations of the natural radionuclides 238U, 226Ra, 232Th and 40K have been measured by gamma-ray spectrometry in 796 topsoil samples from the Pearl River Delta Zone (PRDZ) of Guangdong, China. The mean concentrations for 238U, 226Ra, 232Th and 40K were found to be 140 +/- 37 Bq kg-1, 134 +/- 41 Bq kg-1, 187 +/- 80 Bq kg-1 and 680 +/- 203 Bq kg-1 dry mass, respectively. These values were all higher than the mean values in soil for China and the world. Outdoor air-absorbed dose rates, calculated from activity concentrations of 226Ra, 232Th and 40K, ranged from 86 to 237 nGy h-1, with a mean value of 165 +/- 46 nGy h-1. The corresponding annual outdoor effective dose rate per person was estimated to be between 0.11 and 0.29 mSv y-1, with a mean value of 0.20 +/- 0.06 mSv y-1, which was also higher than the world mean value of 0.07 mSv y-1. The radium equivalent activity (Ra(eq)) and the external hazard index (I(r)) resulted from the natural radionuclides in soil, were also calculated and found to vary from 230 to 676 Bq kg-1 and from 0.6 to 1.8, respectively. The Ra(eq) and the I(r) in all the investigated regions were up to 75% higher than the set limits of 370 Bq kg-1 and 1.0, respectively. PMID- 22036159 TI - Long-distance transport of pertechnetate in the moonflower (Ipomoea alba). AB - The first research on the transport of metastable-technetium-99 ((99m)Tc) in the form of pertechnetate ((99m)TcO4-) within plants suggested that (99m)TcO4- may be mobile in the phloem. In contrast, more recent evidence indicates the anion is transported in the xylem. Here we demonstrate that observations of (99m)Tc transport in the test subject of these initial investigations, the moonflower (Ipomoea alba L.), are incompatible with phloem flow. Rather, the presence of only minute amounts of (99m)Tc in typical sinks for phloem solutes and (99m)Tc transport out of labeled leaves when shaded but not when illuminated strongly suggest that the radionuclide is transported in the xylem. The study increases confidence in the identification of (99m)TcO4- as a xylem mobile compound whose distribution in plants can be visualized using nuclear medicine scintigraphic imaging techniques. PMID- 22036160 TI - Using 210Pb measurements to estimate sedimentation rates on river floodplains. AB - Growing interest in the dynamics of floodplain evolution and the important role of overbank sedimentation on river floodplains as a sediment sink has focused attention on the need to document contemporary and recent rates of overbank sedimentation. The potential for using the fallout radionuclides 137Cs and excess 210Pb to estimate medium-term (10-102 years) sedimentation rates on river floodplains has attracted increasing attention. Most studies that have successfully used fallout radionuclides for this purpose have focused on the use of 137Cs. However, the use of excess 210Pb potentially offers a number of advantages over 137Cs measurements. Most existing investigations that have used excess 210Pb measurements to document sedimentation rates have, however, focused on lakes rather than floodplains and the transfer of the approach, and particularly the models used to estimate the sedimentation rate, to river floodplains involves a number of uncertainties, which require further attention. This contribution reports the results of an investigation of overbank sedimentation rates on the floodplains of several UK rivers. Sediment cores were collected from seven floodplain sites representative of different environmental conditions and located in different areas of England and Wales. Measurements of excess 210Pb and 137Cs were made on these cores. The 210Pb measurements have been used to estimate sedimentation rates and the results obtained by using different models have been compared. The 137Cs measurements have also been used to provide an essentially independent time marker for validation purposes. In using the 210Pb measurements, particular attention was directed to the problem of obtaining reliable estimates of the supported and excess or unsupported components of the total 210Pb activity of sediment samples. Although there was a reasonable degree of consistency between the estimates of sedimentation rate provided by the 137Cs and excess 210Pb measurements, some differences existed and the various models used to interpret excess 210Pb measurements could produce different results. By using the 137Cs measurements to provide independent validation of the estimates of sedimentation rate provided by the different models used with the excess 210Pb measurement it was shown that the CICCS and Composite CRS models appeared to generally provide the best results. PMID- 22036161 TI - The concentration of free Ca(2+) in the sarcoplasmic reticulum of frog cut twitch skeletal muscle fibers estimated with tetramethylmurexide. AB - One aim of this article was to determine the resting concentration of free Ca(2+) in the sarcoplasmic reticulum (SR) of frog cut skeletal muscle fibers ([Ca(2+)](SR,R)) using the calcium absorbance indicator dye tetramethylmurexide (TMX). Another was to determine the ratio of [Ca(2+)](SR,R) to TMX's apparent dissociation constant for Ca(2+) (K(app)) in order to establish the capability of monitoring [Ca(2+)](SR)(t) during SR Ca(2+) release - a signal needed to determine the Ca(2+) permeability of the SR. To reveal the properties of TMX in the SR, the surface membrane was rapidly permeabilized with saponin to rapidly dissipate myoplasmic TMX. Results indicated that the concentration of Ca-free TMX in the SR was 2.8-fold greater than that in the myoplasm apparently due to binding of TMX to sites in the SR. Taking into account that such binding might influence K(app) as well as a dependence of K(app) on TMX concentration, the results indicate an average [Ca(2+)](SR,R) ranging from 0.43 to 1.70mM. The ratio [Ca(2+)](SR,R)/K(app) averaged 0.256, a relatively low value which should not depend on factors influencing K(app). As a result, the time course of [Ca(2+)](SR)(t) in response to electrical stimulation is well determined by, and approximately linearly related to, the active TMX absorbance signal. PMID- 22036162 TI - Response to "Stereotactic ablative radiotherapy in the framework of classical radiobiology: response to Drs. Brown, Diehn, and Loo." (Int J Radiat Oncol Biol Phys 2011;79:1599-1600) and "Influence of tumor hypoxia on stereotactic ablative radiotherapy (SABR): response to Drs. Mayer and Timmerman." (Int J Radiation Oncol Biol Phys 2011;78:1600). PMID- 22036166 TI - Response to "Risk of all-cause and prostate cancer-specific mortality after brachytherapy in men with small prostate size" (Int J Radiat Oncol Biol Phys 2011;79:1318-1322). PMID- 22036168 TI - Translational gastrointestinal pharmacology in the 21st century: 'the lesogaberan story'. AB - The development of the novel gamma-aminobutyric acid type-B receptor (GABAB) agonist lesogaberan is presented as an example of a partly successful translational strategy in the field of gastroenterology. Data on transient lower esophageal sphincter relaxations (TLESRs) and gastroesophageal reflux inhibition from preclinical models translated well to clinical studies in healthy volunteers and patients with gastroesophageal reflux disease (GERD). Animal models have also been used successfully to predict the effect of other target mechanisms on TLESRs in humans. However, while translation of physiology to symptomatology in patients with GERD was achieved, the effect size was too small to be of clinical significance. A deeper understanding of the cause of symptoms in different patient categories is therefore required. PMID- 22036169 TI - Subcellular signaling in the endothelium: cyclic nucleotides take their place. AB - When lecturing on the topic of cellular signaling I have had occasion to ask the class for examples of cellular processes NOT impacted by cyclic AMP (cAMP) and am struck by how few examples exist. Indeed, studies spanning the past 60 years have detailed how this ubiquitous second messenger impacts virtually all cellular processes, including intermediary metabolism, contractility, motility, proliferation, and gene expression in most mammalian cells. Since the hydrophobic cAMP could in principle diffuse rapidly throughout the cell once formed, the remarkable spatial and temporal specificity of its numerous actions in cells is truly impressive. Herein I introduce the main players involved in coordinating actions of cAMP in vascular endothelial cells (VECs), and focus on the increasing awareness of the dominant role that cyclic nucleotide phosphodiesterases (PDEs), the sole cellular enzymes capable of hydrolytically inactivating cAMP, play in fostering this specificity. PMID- 22036170 TI - Purinergic system, microglia and neuropathic pain. AB - Extracellular nucleotides play pivotal roles in the regulation of neuronal and glial functions in the nervous system through P2X receptors (P2XRs) and P2Y receptors (P2YRs). A growing body of evidence shows that microglia express several subtypes of P2XRs and P2YRs, and that these receptors play a key role in pain signaling in the spinal cord under pathological conditions, such as following peripheral nerve injury (neuropathic pain). Following peripheral nerve injury, dorsal horn microglia become activated and show upregulated expression of purinergic receptors, and interference with the function or expression of these receptors strongly suppresses neuropathic pain. This article highlights recent advances that further increase our understanding of the mechanisms by which microglial purinergic receptors contribute to the pathogenesis of neuropathic pain. PMID- 22036171 TI - Mutations in POLR3A and POLR3B encoding RNA Polymerase III subunits cause an autosomal-recessive hypomyelinating leukoencephalopathy. AB - Congenital hypomyelinating disorders are a heterogeneous group of inherited leukoencephalopathies characterized by abnormal myelin formation. We have recently reported a hypomyelinating syndrome characterized by diffuse cerebral hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). We performed whole-exome sequencing of three unrelated individuals with HCAHC and identified compound heterozygous mutations in POLR3B in two individuals. The mutations include a nonsense mutation, a splice-site mutation, and two missense mutations at evolutionally conserved amino acids. Using reverse transcription-PCR and sequencing, we demonstrated that the splice-site mutation caused deletion of exon 18 from POLR3B mRNA and that the transcript harboring the nonsense mutation underwent nonsense-mediated mRNA decay. We also identified compound heterozygous missense mutations in POLR3A in the remaining individual. POLR3A and POLR3B encode the largest and second largest subunits of RNA Polymerase III (Pol III), RPC1 and RPC2, respectively. RPC1 and RPC2 together form the active center of the polymerase and contribute to the catalytic activity of the polymerase. Pol III is involved in the transcription of small noncoding RNAs, such as 5S ribosomal RNA and all transfer RNAs (tRNA). We hypothesize that perturbation of Pol III target transcription, especially of tRNAs, could be a common pathological mechanism underlying POLR3A and POLR3B mutations. PMID- 22036172 TI - Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy. AB - Mutations in POLR3A encoding the largest subunit of RNA polymerase III (Pol III) were found to be responsible for the majority of cases presenting with three clinically overlapping hypomyelinating leukodystrophy phenotypes. We uncovered in three cases without POLR3A mutation recessive mutations in POLR3B, which codes for the second largest subunit of Pol III. Mutations in genes coding for Pol III subunits are a major cause of childhood-onset hypomyelinating leukodystrophies with prominent cerebellar dysfunction, oligodontia, and hypogonadotropic hypogonadism. PMID- 22036173 TI - [Imported malaria in adults. Clinical, epidemiological and analytical features]. AB - INTRODUCTION: Up to now, the epidemiological and clinical features of imported malaria in Spain have been described in small series from general hospitals. Almost all diagnosis had been made based on symptomatic patients. The aim of this study has been to determine the epidemiological, clinical and laboratorial characteristics of imported malaria in a Reference Unit for Tropical Diseases. PATIENTS AND METHODS: We performed a cross-sectional, observational and retrospective study. The series consisted of patients diagnosed of malaria who had been attended at the Hospital Carlos III from January 1, 2002 to December 31, 2007. RESULTS: We identified 484 episodes of malaria, of which 398 cases were included in the analysis. Almost 50% of the patients were natives of endemic areas, while the rest were native-travelers or travelers. Most cases (88-98% according to the group) had not taken malaria chemoprophylaxis correctly when indicated. At the time of diagnosis, 30.4% of patients were asymptomatic and 28.1% of asymptomatic patients had anemia, 19.8% thrombocytopenia, 14% leukopenia, 5% hypocholesterolemia, 5% renal failure and 4.1% hypoglycemia. Low parasitemia was present in 97.5% of asymptomatic individuals compared to 80.5% of the symptomatic patients (P<0.001). DISCUSSION: Absence of chemoprophylaxis (or poor compliance) is the main reason for malaria in individuals traveling to endemic areas. Malaria must be ruled out in individuals coming from tropical countries with compatible symptoms, and it also should be suspected in certain groups of asymptomatic individuals with abnormal laboratorial parameters. PMID- 22036174 TI - Glucagon-like peptide 1 (GLP-1) in the gastrointestinal tract of the pheasant (Phasianus colchicus). AB - The distribution of Glucagon-like peptide 1 (GLP-1) was investigated in the gastrointestinal tract of the pheasant using immunohistochemistry. GLP-1 immunoreactive cells were common in the small intestine, in the proventriculus and in the pancreas. Immunostained cells were not seen in the crop, in the gizzard and in the large intestine. Double labelling demonstrated that GLP-1 and pituitary adenylate cyclase-activating polypeptide (PACAP) were occasionally co localized only in the duodenal villi. In contrast to what was previously described in the chicken and ostrich, we noted GLP-1 positive cells in the duodenum. These data were consistent with the presence of proglucagon mRNA in the chicken duodenum. Our findings indicate that GLP-1 might have an inhibitory effect on gastric and crop emptying and on acid secretion also in the pheasant. Moreover, the results of the present research regarding the initial region of the small intestine suggest a further direct mechanism of the GLP-1 release during the early digestion phase and an enhancement of its incretin role. PMID- 22036175 TI - [Massive intestinal ischaemia]. PMID- 22036176 TI - [Complications after pancreaticoduodenectomy]. AB - The most frequent complications after pancreaticoduodenectomy are analysed in this review. These include, delayed gastric emptying, pancreatic fistula, post operative bleeding, and the complications after vascular reconstruction in the cases of locally extended pancreatic cancer. For this, randomised prospective studies, systematic meta-analyses and clinical guidelines on the definition, clinical severity grade and treatment of these complications have been evaluated. PMID- 22036177 TI - Dreamed movement elicits activation in the sensorimotor cortex. AB - Since the discovery of the close association between rapid eye movement (REM) sleep and dreaming, much effort has been devoted to link physiological signatures of REM sleep to the contents of associated dreams [1-4]. Due to the impossibility of experimentally controlling spontaneous dream activity, however, a direct demonstration of dream contents by neuroimaging methods is lacking. By combining brain imaging with polysomnography and exploiting the state of "lucid dreaming," we show here that a predefined motor task performed during dreaming elicits neuronal activation in the sensorimotor cortex. In lucid dreams, the subject is aware of the dreaming state and capable of performing predefined actions while all standard polysomnographic criteria of REM sleep are fulfilled [5, 6]. Using eye signals as temporal markers, neural activity measured by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) was related to dreamed hand movements during lucid REM sleep. Though preliminary, we provide first evidence that specific contents of REM-associated dreaming can be visualized by neuroimaging. PMID- 22036178 TI - Seaweed communities in retreat from ocean warming. AB - In recent decades, global climate change [1] has caused profound biological changes across the planet [2-6]. However, there is a great disparity in the strength of evidence among different ecosystems and between hemispheres: changes on land have been well documented through long-term studies, but similar direct evidence for impacts of warming is virtually absent from the oceans [3, 7], where only a few studies on individual species of intertidal invertebrates, plankton, and commercially important fish in the North Atlantic and North Pacific exist. This disparity of evidence is precarious for biological conservation because of the critical role of the marine realm in regulating the Earth's environmental and ecological functions, and the associated socioeconomic well-being of humans [8]. We interrogated a database of >20,000 herbarium records of macroalgae collected in Australia since the 1940s and documented changes in communities and geographical distribution limits in both the Indian and Pacific Oceans, consistent with rapid warming over the past five decades [9, 10]. We show that continued warming might drive potentially hundreds of species toward and beyond the edge of the Australian continent where sustained retreat is impossible. The potential for global extinctions is profound considering the many endemic seaweeds and seaweed-dependent marine organisms in temperate Australia. PMID- 22036179 TI - Temporal dynamics of bacterial aging and rejuvenation. AB - Single-celled organisms dividing by binary fission were thought not to age [1-4]. A 2005 study by Stewart et al. [5] reversed the dogma by demonstrating that Escherichia coli were susceptible to aging. A follow-up study by Wang et al. [6] countered those results by demonstrating that E. coli cells trapped in microfluidic devices are able to sustain robust growth without aging. The present study reanalyzed these conflicting data by applying a population genetic model for aging in bacteria [7]. Our reanalysis showed that in E. coli, as predicted by the model, (1) aging and rejuvenation occurred simultaneously in a population; (2) lineages receiving sequentially the maternal old pole converged to a stable attractor state; (3) lineages receiving sequentially the maternal new pole converged to an equivalent but separate attractor state; (4) cells at the old pole attractor had a longer doubling time than ones at the new pole attractor; and (5) the robust growth state identified by Wang et al. corresponds to our predicted attractor for lineages harboring the maternal old pole. Thus, the previous data, rather than opposing each other, together provide strong evidence for bacterial aging. PMID- 22036180 TI - A head view-invariant representation of gaze direction in anterior superior temporal sulcus. AB - Humans show a remarkable ability to discriminate others' gaze direction, even though a given direction can be conveyed by many physically dissimilar configurations of different eye positions and head views. For example, eye contact can be signaled by a rightward glance in a left-turned head or by direct gaze in a front-facing head. Such acute gaze discrimination implies considerable perceptual invariance. Previous human research found that superior temporal sulcus (STS) responds preferentially to gaze shifts [1], but the underlying representation that supports such general responsiveness remains poorly understood. Using multivariate pattern analysis (MVPA) of human functional magnetic resonance imaging (fMRI) data, we tested whether STS contains a higher order, head view-invariant code for gaze direction. The results revealed a finely graded gaze direction code in right anterior STS that was invariant to head view and physical image features. Further analyses revealed similar gaze effects in left anterior STS and precuneus. Our results suggest that anterior STS codes the direction of another's attention regardless of how this information is conveyed and demonstrate how high-level face areas carry out fine-grained, perceptually relevant discrimination through invariance to other face features. PMID- 22036181 TI - A pathway for synapsis initiation during zygotene in Drosophila oocytes. AB - Formation of the synaptonemal complex (SC), or synapsis, between homologs in meiosis is essential for crossing over and chromosome segregation [1-4]. How SC assembly initiates is poorly understood but may have a critical role in ensuring synapsis between homologs and regulating double-strand break (DSB) and crossover formation. We investigated the genetic requirements for synapsis in Drosophila and found that there are three temporally and genetically distinct stages of synapsis initiation. In "early zygotene" oocytes, synapsis is only observed at the centromeres. We also found that nonhomologous centromeres are clustered during this process. In "mid-zygotene" oocytes, SC initiates at several euchromatic sites. The centromeric and first euchromatic SC initiation sites depend on the cohesion protein ORD. In "late zygotene" oocytes, SC initiates at many more sites that depend on the Kleisin-like protein C(2)M. Surprisingly, late zygotene synapsis initiation events are independent of the earlier mid-zygotene events, whereas both mid and late synapsis initiation events depend on the cohesin subunits SMC1 and SMC3. We propose that the enrichment of cohesion proteins at specific sites promotes homolog interactions and the initiation of euchromatic SC assembly independent of DSBs. Furthermore, the early euchromatic SC initiation events at mid-zygotene may be required for DSBs to be repaired as crossovers. PMID- 22036182 TI - Synaptonemal complex-dependent centromeric clustering and the initiation of synapsis in Drosophila oocytes. AB - The pairing of homologous chromosomes and the intimate synapsis of the paired homologs by the synaptonemal complex (SC) are essential for subsequent meiotic processes including recombination and chromosome segregation. Here we show that the centromere clustering plays an important role in initiating homolog synapsis during meiosis in Drosophila females. Although centromeres are not clustered prior to the onset of meiosis, all four pairs of centromeres are actively clustered into one or two masses during early meiotic prophase. Within the 16 cell cyst, centromeric clustering appears to define the first step in the initiation of synapsis. Clustering is restricted to the nuclei that form the SC and is dependent on all known SC proteins. Surprisingly, both centromeric clusters and the SC components associated with them persist long after the disassembly of the euchromatic SC at the end of pachytene. The initiation of homologous recombination through the formation of programmed double-strand breaks (DSBs) is not required for either the formation or the maintenance of the centromeric clusters. Our data support a view in which the SC-mediated clustering at the centromeres is the initiating event for meiotic synapsis. PMID- 22036183 TI - Stimulation of category-selective brain areas modulates ERP to their preferred categories. AB - Neural selectivity to specific object categories has been demonstrated in extrastriate cortex with both functional MRI [1-3] and event-related potential (ERP) [4, 5]. Here we tested for a causal relationship between the activation of category-selective areas and ERP to their preferred categories. Electroencephalogram (EEG) was recorded while participants observed faces and headless bodies. Concurrently with EEG recording, we delivered two pulses of transcranial magnetic stimulation (TMS) over the right occipital face area (OFA) or extrastriate body area (EBA) at 60 and 100 ms after stimulus onset. Results showed a clear dissociation between the stimulated site and the stimulus category on ERP modulation: stimulation of the OFA significantly increased the N1 amplitude to faces but not to bodies, whereas stimulation of the EBA significantly increased the N1 amplitude to bodies but not to faces. These findings provide the first evidence for a specific and causal link between activity in category-selective networks and scalp-recorded ERP to their preferred categories. This result also demonstrates that the face and body N1 reflects several nonoverlapping neural sources, rather than changes in face-selective mechanisms alone. Lastly, because early stimulation (60-100 ms) affected selectivity of a later ERP component (150-200 ms), the results could imply a feed forward connection between occipital and temporal category-selective areas. PMID- 22036184 TI - Optic flow cues guide flight in birds. AB - Although considerable effort has been devoted to investigating how birds migrate over large distances, surprisingly little is known about how they tackle so successfully the moment-to-moment challenges of rapid flight through cluttered environments [1]. It has been suggested that birds detect and avoid obstacles [2] and control landing maneuvers [3-5] by using cues derived from the image motion that is generated in the eyes during flight. Here we investigate the ability of budgerigars to fly through narrow passages in a collision-free manner, by filming their trajectories during flight in a corridor where the walls are decorated with various visual patterns. The results demonstrate, unequivocally and for the first time, that birds negotiate narrow gaps safely by balancing the speeds of image motion that are experienced by the two eyes and that the speed of flight is regulated by monitoring the speed of image motion that is experienced by the two eyes. These findings have close parallels with those previously reported for flying insects [6-13], suggesting that some principles of visual guidance may be shared by all diurnal, flying animals. PMID- 22036186 TI - The impact of maxillary advancement on breathing parameters in class III patients. PMID- 22036185 TI - Phytochrome regulation of cellulose synthesis in Arabidopsis. AB - Plant development is highly plastic and dependent on light quantity and quality monitored by specific photoreceptors. Although we have a detailed knowledge of light signaling pathways, little is known about downstream targets involved in growth control. Cell size and shape are in part controlled by cellulose microfibrils extruded from large cellulose synthase complexes (CSCs) that migrate in the plasma membrane along cortical microtubules. Here we show a role for the red/far-red light photoreceptor PHYTOCHROME B (PHYB) in the regulation of cellulose synthesis in the growing Arabidopsis hypocotyl. In this organ, CSCs contains three distinct cellulose synthase (CESA) isoform classes: nonredundant CESA1 and CESA3 and a third class represented by partially redundant CESA2, CESA5, and CESA6. Interestingly, in the dark, depending on which CESA subunits occupy the third position, CSC velocity is more or less inhibited through an interaction with microtubules. Activation of PHYB overrules this inhibition. The analysis of cesa5 mutants shows a role for phosphorylation in the control of CSC velocity. These results, combined with the cesa5 mutant phenotype, suggest that cellulose synthesis is fine tuned through the regulated interaction of CSCs with microtubules and that PHYB signaling impinges on this process to maintain cell wall strength and growth in changing environments. PMID- 22036188 TI - Follicle features in adolescent and young adult women with Hodgkin's disease prior to chemotherapy: a preliminary report. AB - Treatment of Hodgkin's disease (HD) has improved over the last two decades, but infertility is a common side effect of chemotherapy. Men with HD have an increased risk of inadequate semen quality and severe damage of fertility before treatment. The aim of this study was to investigate the possible association between the disease itself and germ-cell damage in female patients before treatment for HD. The ovarian cortex from 13 untreated women with HD was processed by light and transmission electron microscopy and compared with the ovarian cortex from the control group of 13 untreated women without HD. Histological examination of fresh ovarian cortex showed that in HD patients, follicles presented an unusual presence of clear vacuoles when compared with control group (73.7% versus 5.7%). Ultrastructural examination demonstrated that the small vacuoles fused into large autophagic vacuoles. The percentage of vacuolated follicles was higher in patients with advanced stage and bulky disease. In conclusion, this study demonstrates for the first time that significant damage to gametes occurs in women with HD. Further investigations are required to establish whether the present features should be considered a common side effect of HD. PMID- 22036187 TI - Dysbalance of cortical inhibition and excitation in abstinent cocaine-dependent patients. AB - The effects of chronic cocaine dependence on cortical inhibitory/excitatory processes are not well characterized. Employing transcranial magnetic stimulation measures of motor cortical excitability, we have previously reported an elevation of motor threshold (MT) suggesting reduced excitability and an increased long interval intracortical facilitation (LICF) suggesting increased excitability. In the current study, we used an expanded battery of TMS cortical excitability measures to further examine motor cortex excitability in a larger sample of well characterized and closely monitored for drug use, abstinent cocaine-dependent subjects (N = 52) and healthy controls (N = 42). Furthermore, coil-to-cortex distance was assessed in a subsample of both groups. We verified that long interval intracortical facilitation (LICF), possibly representing glutamatergic cortical neurotransmission, was significantly increased in cocaine-dependent patients. Significantly longer cortical silent periods (CSP) and elevated MT were also observed while there was no significant abnormality in long-interval intracortical inhibition (LICI). Increased LICF and CSP duration suggest increased cortical excitability and increased inhibition, respectively, of different neurotransmitter systems in cocaine-dependent patients. Increased MT might reflect an adaptation to those effects of cocaine abuse that enhance cortical excitability. Overall, the data point to the complex nature of chronic cocaine dependence on the balance of cortical inhibitory/excitatory mechanisms. PMID- 22036189 TI - Quinn's advantage fertilization medium enhances zona pellucida-induced acrosome reaction compared with human tubal fluid medium. AB - The aim of this study was to compare sperm velocity, hyperactivation, zona pellucida (ZP) binding and ZP-induced acrosome reaction (AR) between Quinn's advantage fertilization (QAF), human tubal fluid (HTF) and Ham's F10 media. Semen samples were obtained from normozoospermic men and motile spermatozoa were prepared by gradient centrifugation (PureSperm). Unfertilized oocytes from clinical IVF were used for spermatozoa-oocyte interaction tests. Sperm velocity and hyperactivation were assessed using a Hamilton-Thorn motility analyser. When media were supplemented with human albumin, sperm motility and velocity and sperm binding were not significantly different between QAF and HTF. However, ZP-induced AR was significantly higher with QAF than HTF (42+/-22 versus 21+/-18, P<0.th001). Sperm velocity, hyperactivation and sperm binding were also significantly higher in QAF than Ham's F10 media. Supplementation of media with either human serum or human albumin showed no difference in effect on all sperm test results. In conclusion, QAF medium significantly enhances ZP-induced AR which is essential for sperm penetration. Thus QAF appears to be a better medium than HTF for sperm fertilizing ability in conventional IVF. PMID- 22036190 TI - Glucose/lactate metabolism of cryopreserved intact bovine ovaries as a novel quantitative marker to assess tissue cryodamage. AB - For some patients, the autotransplantation of a cryopreserved-thawed intact ovary might be the best option to preserve their reproductive potential after fertility threatening treatment. The best procedure to successfully cryopreserve a human ovary without inflicting a devastating level of cryodamage is to date unknown. To optimize this procedure, this study developed an assay to monitor the extent of cryodamage inflicted on bovine ovarian tissue by different cryopreservation protocols. The assay measures glucose and lactate metabolism of ovarian tissue fragments in vitro and determines the extent of cryodamage in cryopreserved ovaries. This study tested the cryoprotective effect of two different routes of administration of the cryoprotectant dimethylsulphoxide (DMSO). The cryoprotective effect was assessed in different tissue layers of the ovary, namely the cortex, the subcortex and the medulla. Submersion of intact ovaries in DMSO prior to freezing-thawing resulted in the complete protection of the glucose/lactate metabolism of the cortex, but not of the inner ovarian mass. Perfusion without simultaneous submersion, resulted in partial protection of cortex, subcortex and medulla, while the combination of submersion and perfusion conveyed the highest level of protection for all three ovarian tissue layers. PMID- 22036191 TI - [Comparison of hot versus cold biopsy forceps in the diagnosis of endobronchial lesions]. AB - INTRODUCTION: Traditionally cold biopsy forceps were used for endobronchial biopsy, and recently electrocautery (hot) bronchoscopy biopsy forceps are introduced. It is hypothesized that hot biopsy forceps may decrease procedure related bleeding and also may decrease the quality of obtained samples. PATIENTS AND METHODS: Patients with different indications for endobronchial biopsy during fiberoptic bronchoscopy underwent three hot and three cold biopsies with a random fashion. All biopsies were obtained with a single biopsy forceps with and without the application of an electrocoagulation current, set on soft coagulation mode (40W). A four point scale was used for quantification of bleeding. A single pathologist blinded to the patients' history was requested to review all samples. A three point scale was used to assess electrocoagulation damage. RESULTS: A total of 240 biopsies were obtained from 40 patients. Frequency of positive concordance between the two methods was 85%. The degree of electrocoagulation damage of the samples was as follows: grade 1=52.5%, grade 2=32.5%, and grade 3=15%. The average bleeding score following hot biopsy was significantly lower compared to the cold biopsy (P=.006). The concordance between diagnostic yield of hot and cold biopsies was 85%. There was no significant difference between the diagnostic yields of two biopsy methods (P=.687). CONCLUSIONS: Hot biopsy forceps significantly decreased the procedure related bleeding. The quality of samples was not impaired significantly. Regarding low prevalence of bleeding following endobronchial biopsy, routine use of hot bronchoscopy forceps is not reasonable. However, familiarity of bronchoscopists with this method may improve bronchoscopy safety. PMID- 22036192 TI - Support for an expanded tripartite influence model with gay men. AB - This study investigated whether an expanded tripartite influence model would represent gay men's experiences. This model was extended by adding partners and gay community involvement as sources of social influence and considering dual body image pathways (muscularity and body fat dissatisfaction) to muscularity enhancement and disordered eating behaviors. Latent variable structural equation modeling analyses upheld this model for 346 gay men. Dual body image pathways to body change behaviors were supported, although three unanticipated interrelationships emerged, suggesting that muscularity and body fat concerns and behaviors may be more integrated for gay men. Internalization of the mesomorphic ideal, appearance comparison, muscularity dissatisfaction, and body fat dissatisfaction were key mediators in the model. Of the sources of social influence, friend and media pressure to be lean, gay community involvement, and partner, friend, media, and family pressures to be muscular made incremental contributions. Unexpectedly, certain sources were directly connected to body change behaviors. PMID- 22036193 TI - Evaluation of sentinel surveillance system for monitoring hand, foot and mouth disease in Hong Kong. AB - OBJECTIVES: A sentinel surveillance system (SSS) was set up in Hong Kong to monitor hand, foot and mouth disease (HFMD) trends. This evaluation assessed the performance of the SSS from 2001 to 2009, and aimed to identify areas for improvement. STUDY DESIGN: A retrospective review using structured guidelines for evaluating public health surveillance systems published by the US Centers for Disease Control and Prevention. METHODS: The effectiveness of the SSS was evaluated using routine service statistics, laboratory surveillance data, and results of an acceptability survey conducted among the sentinel doctors. This information was used to assess various attributes of the SSS including simplicity, flexibility, data quality, usefulness, sensitivity, specificity, positive predictive value (PPV), representativeness, timeliness and acceptability. RESULTS: The SSS was simple and flexible with high-quality data. It correlated well with the laboratory surveillance data (P < 0.001) and facilitated early detection of community epidemics. It helped to identify seasonal trends and high-risk groups. Specificity was high (83.4-88.5%), while sensitivity and PPV were borderline satisfactory (38.4-56.8%). The sentinel clinics were representative of the population distribution. The SSS was acceptable to the sentinel doctors, but 17.9-28.2% of them had delays in reporting. CONCLUSIONS: The SSS is effective for monitoring HFMD trends in Hong Kong, and is useful for initiating preventive measures. PMID- 22036194 TI - Legal interventions to reduce alcohol-related cancers. AB - Research and public policy literature on alcohol-related harm predominantly focuses on the impact of alcohol policies over the short term. However, evidence on the effect of interventions on long-term, alcohol-related chronic disease, including cancers, is growing. The experience from tobacco control supports the use of interventions that increase the price of a commodity and restrict its availability in order to reduce consumption and realize long-term health gains. Meanwhile, the negative involvement of the alcohol industry in alcohol policy development is hampering efforts to intervene early and potentially save many lives. As the burden of alcohol-related cancers becomes more apparent, effective alcohol policies should be introduced sooner rather than later. This paper looks at some of the key legal interventions to reduce alcohol consumption, the potential for these interventions to reduce the risk of alcohol-related cancers, and some of the barriers to implementing these interventions. Examples of law reform efforts in Australia, New Zealand and the UK are given, as well as a short discussion of global alcohol policy initiatives. PMID- 22036195 TI - Evidence for functional trace amine associated receptor-1 in normal and malignant B cells. AB - Following the observation that dopaminergic components are present in normal and malignant B cells, we now provide evidence that they additionally express the functionally related trace amine-associated receptor-1 (TAAR1). Immunodetectable TAAR1 was found in lines derived from a broad range of B-cell malignancy; and in tonsillar B cells, particularly when activated. L3055 Burkitt's lymphoma cells were shown to respond to prototypical TAAR1 agonists in cytotoxicity assays with features of apoptotic death evident; normal B cells were somewhat less sensitive to the agonists. These data raise the possibility that TAAR1 may have therapeutic relevance to leukemia, lymphoma, and wider B-cell pathologies. PMID- 22036196 TI - A regional flux-based risk assessment approach for multiple contaminated sites on groundwater bodies. AB - In the context of the Water Framework Directive (EP and CEU, 2000), management plans have to be set up to monitor and to maintain water quality in groundwater bodies in the EU. In heavily industrialized and urbanized areas, the cumulative effect of multiple contaminant sources is likely and has to be evaluated. In order to propose adequate measures, the calculated risk should be based on criteria reflecting the risk of groundwater quality deterioration, in a cumulative manner and at the scale of the entire groundwater body. An integrated GIS- and flux-based risk assessment approach for groundwater bodies is described, with a regional scale indicator for evaluating the quality status of the groundwater body. It is based on the SEQ-ESO currently used in the Walloon Region of Belgium which defines, for different water uses and for a detailed list of groundwater contaminants, a set of threshold values reflecting the levels of water quality and degradation with respect to each contaminant. The methodology is illustrated with first results at a regional scale on a groundwater body-scale application to a contaminated alluvial aquifer which has been classified to be at risk of not reaching a good quality status by 2015. These first results show that contaminants resulting from old industrial activities in that area are likely to contribute significantly to the degradation of groundwater quality. However, further investigations are required on the evaluation of the actual polluting pressures before any definitive conclusion be established. PMID- 22036197 TI - Modeling cellular processes in 3D. AB - Recent advances in photonic imaging and fluorescent protein technology offer unprecedented views of molecular space-time dynamics in living cells. At the same time, advances in computing hardware and software enable modeling of ever more complex systems, from global climate to cell division. As modeling and experiment become more closely integrated we must address the issue of modeling cellular processes in 3D. Here, we highlight recent advances related to 3D modeling in cell biology. While some processes require full 3D analysis, we suggest that others are more naturally described in 2D or 1D. Keeping the dimensionality as low as possible reduces computational time and makes models more intuitively comprehensible; however, the ability to test full 3D models will build greater confidence in models generally and remains an important emerging area of cell biological modeling. PMID- 22036198 TI - Extracellular matrix determinants of proteolytic and non-proteolytic cell migration. AB - Cell invasion into the 3D extracellular matrix (ECM) is a multistep biophysical process involved in inflammation, tissue repair, and metastatic cancer invasion. Migrating cells navigate through tissue structures of complex and often varying physicochemical properties, including molecular composition, porosity, alignment and stiffness, by adopting strategies that involve deformation of the cell and engagement of matrix-degrading proteases. We review how the ECM determines whether or not pericellular proteolysis is required for cell migration, ranging from protease-driven invasion and secondary tissue destruction, to non proteolytic, non-destructive movement that solely depends on cell deformability and available tissue space. These concepts call for therapeutic targeting of proteases to prevent invasion-associated tissue destruction rather than the migration process per se. PMID- 22036199 TI - Convergent and discriminant validity of attenuated psychosis screening tools. AB - Brief self-report questionnaires that assess attenuated psychotic symptoms have the potential to screen many people who may benefit from clinical monitoring, further evaluation, or early intervention. The extent to which recently developed screening instruments demonstrate sound psychometric properties is an important issue toward the implementation of these measures in clinical practice. This study examines the convergent validity, discriminant validity, and test-retest reliability of four recently developed screening instruments. Screening instruments were included in an assessment battery and administered to a sample of 355 college students. Screening scores support the convergent and discriminant validity and the test-retest reliability of these measures. PMID- 22036201 TI - Perioperative surgical care bundle reduces pancreaticoduodenectomy wound infections. AB - BACKGROUND: Pancreaticoduodenectomy (PD) is a complex surgical procedure with a historically high morbidity rate. The goal of this study was to determine if the implementation of a 12-measure perioperative surgical care bundle (SCB) was successful in reducing infectious and other complications in patients undergoing PD compared with a routine preoperative preparation group (RPP). METHODS: In this retrospective cohort study utilizing the HPB surgery database at the Thomas Jefferson University, we analyzed clinical data from 233 consecutive PDs from October 2005 to May 2008 on patients who underwent RPP, and compared them with 233 consecutive PDs from May 2008 to May 2010 following the implementation of the SCB. The SCB was the product of multidisciplinary discussion and extensive literature review. RESULTS: The RPP group and the SCB group had similar demographic characteristics. The overall rate of postoperative morbidity was similar between groups (42.1% versus 37.8%). However, wound infections were significantly lower in the SCB group (15.0% versus 7.7%, P = 0.01).The rates of other common complications, as well as postoperative hospital length of stay, readmissions, and 30-d postoperative mortality were similar between groups. CONCLUSIONS: The implementation of a SCB was followed by a significant decline in wound infection in patients undergoing PD. PMID- 22036200 TI - Selection for tetracycline-resistant Chlamydia suis in treated pigs. AB - The aim of this study was to investigate Chlamydia suis in a pig farm with an outbreak of conjunctivitis and diarrhea. Eye swabs and pooled fecal samples were investigated for the presence of C. suis by real-time PCR and ArrayTube microarray. Samples positive for C. suis by ArrayTube microarray assay were further tested for the presence of the tet(C) resistance gene by PCR. In the first examination, C. suis was identified in 12 six-week-old pigs showing conjunctivitis. Of these, the tet(C) gene-coding region was amplified in one pooled fecal sample and one eye swab, respectively. After oral treatment with tetracycline, clinical symptoms disappeared. Subsequently, all eye swabs investigated from 10 healthy pigs were positive for C. suis and the tet(C) gene coding region. The present study reports rapid selection for tetracycline resistant C. suis after antibiotic treatment. PMID- 22036202 TI - Extracorporeal photopheresis in the treatment of chronic graft-versus-host disease. The Hellenic experience: a study by the Hellenic association of hematology. AB - The Hellenic experience regarding the efficacy of extracorporeal photopheresis (ECP) in the treatment of 58 patients with chronic graft-versus-host disease (cGVHD) is presented in this article. All 58, except one patient, had failed at least one line of immunosuppressive treatment including steroids. Thirty-three out of 58 patients showed an objective overall response to ECP in a median time of 10 weeks after the onset of treatment. The cumulative incidence of overall response was 65.1%. In multivariate analysis, the presence of severe chronic GVHD was the only parameter associated with a significantly lower probability of response to treatment (RR=0.4, CI 95% 0.2-0.9, p=0.03). Responders to treatment with ECP were more likely to discontinue immunosuppression, had a lower probability of non-relapse mortality (RR=0.2, CI 95% 0.1-0.5, p=0.002), and a higher probability of overall survival (RR=7.8, CI 95% 3-20, p<0.001) in comparison with non-responders. Eight out of 58 patients experienced relapse of the original disease. The cumulative incidence of relapse in the group of responders to ECP was 6%, while it was 25% in the group of non-responders to ECP. In multivariate analysis, response to treatment with ECP was the only parameter statistically associated with a significantly decreased hazard of relapse (RR=0.1, CI 95% 0.1-0.7, p=0.02). ECP should be tested as first-line treatment in patients with cGVHD with the aim to minimize the duration of immunosuppression and the rate of relapse of the malignant disease. PMID- 22036203 TI - Comparison between 155 cases of robotic vs. 150 cases of open surgical staging for endometrial cancer. AB - OBJECTIVE: To compare the outcomes of 155 cases of endometrial cancer who had robot-assisted surgical staging to 150 open cases. METHODS: Retrospective chart review of cases of endometrial cancer that underwent staging two different ways by two surgeons at an academic institution. RESULTS: Mean age was 62.4 years in the robotic arm and 65 (P=0.04) in the open arm. Mean body mass index was 34.5 Kg/m(2) in the robotic arm and 33 Kg/m(2) in the open arm (P=0.2). Pelvic and para-aortic lymph node dissection were performed in 94.8% and 67.7% of the robotic cases versus 95.3% and 74% of the open cases, respectively. Mean operative time was 127 min in the robotic arm, and 141 min in the open arm (P=0.0001). Mean lymph node count was 20.3 in the robotic arm, and 20 in the open arm (P=0.567). Mean estimated blood loss was 119 ml in the robotic arm and 185 in the open arm (P=0.015). Mean hospital stay was 1.5 days in the robotic arm, and 4 days in the open arm (P=0.0001). The incidence of postoperative ileus (0.6% vs. 10.7%, P=0.0001), infections (5.2% vs. 24%, P=0.0001), anemia/transfusion (1.3% vs. 7.7%, P=0.005), and cardiopulmonary complications (3.2% vs.14.7%, P=0.003) was significantly lower in the robotic arm vs. the open arm. There was one death in the robotic arm attributed to pre-existing cardiac condition. CONCLUSION: Robotic-assisted staging reaps the benefits of minimally invasive surgery without compromising the adequacy of the procedure. Dedication to the technique shortens the operative time. PMID- 22036204 TI - The effect of junior residents on surgical quality: a study of surgical outcomes in breast surgery. AB - BACKGROUND: Patients are often concerned about the participation of junior trainees in their operative treatment. Breast-conserving therapy (BCT) for nonpalpable breast lesions requires the use of localization devices and carries a significant risk for positive margins of excision. It was therefore hypothesized that the participation of junior residents in BCT operations for nonpalpable breast lesions could result in an increased rate of positive margins of excision. METHODS: Retrospective analysis of a prospective database of all patients with nonpalpable tumors who underwent BCT from August 1999 to August 2009 was performed. Patient and tumor characteristics and factors involved in resection were analyzed. A >=2-mm margin of normal breast tissue beyond tumor was considered an adequate margin. Chi-square analysis and Student's t test were performed to determine relationships between independent variables and margin status. RESULTS: Of 308 BCT procedures for nonpalpable tumors, 241 (78%) were performed by attending surgeons and junior residents (group 1) and 67 (22%) by attending surgeons without resident assistance (group 2). The operations for group 1 took significantly longer than the operations for group 2 (mean, 130 vs 116 min, P = .006). Intraoperative reexcision of margins was performed for 37% of group 1 patients and 31% of group 2 patients (P = .249), and reoperation for inadequate margins was performed in 11% of group 1 patients and 13% of group 2 patients (P = .361). CONCLUSIONS: Junior resident participation in BCT procedures was not associated with higher rates of inadequate margins of excision. Patients can be reassured that junior resident involvement in their BCT operations is safe and effective. PMID- 22036205 TI - Current surgical approach to Paget's disease. AB - BACKGROUND: Paget's disease constitutes between 1% and 3% of all breast malignancies, which makes defining standard surgical therapy difficult. We sought to identify preoperative factors that would select patients for successful breast conservation. METHODS: Fifty-one patients with Paget's disease underwent surgical therapy between October 1998 and January 2010. Clinical presentation of Paget's disease, preoperative imaging, pathologic tumor characteristics, as well as surgical, radiation, and adjuvant therapies were reviewed. RESULTS: Thirty-seven percent underwent breast conservation whereas 63% underwent mastectomy. Twelve patients presented with a palpable mass, and all were treated with mastectomy. Twenty-two patients underwent a mammogram, identifying extensive abnormality requiring mastectomy. Magnetic resonance imaging added to surgical planning in 52% of patients who participated in the study. None of our patients had a local/regional recurrence at 29 months of follow-up evaluation. CONCLUSIONS: Paget's disease of the breast can be treated with breast conservation in a properly selected subset of patients. Successful breast conservation was achieved in patients without a palpable finding, a benign mammogram, and a normal magnetic resonance imaging scan. PMID- 22036206 TI - Use of computed tomography in the initial evaluation of anterior abdominal stab wounds. AB - BACKGROUND: The purpose of this study was to assess the ability of computed tomography (CT) to facilitate initial management decisions in patients with anterior abdominal stab wounds. METHODS: A retrospective review was conducted of patients with anterior abdominal stab wounds who underwent CT over 4.5 years. Any abnormality suspicious for intra-abdominal injury was considered a positive finding on CT. RESULTS: Ninety-eight patients met the study's inclusion criteria. Positive findings on CT were noted in 30 patients (31%), leading to operative intervention in 67%. Injuries were confirmed in 95% of cases, but only 70% were therapeutic. Ten patients had nonoperative management despite positive findings on CT, including 5 patients with solid organ injuries. One patient underwent operative intervention for clinical deterioration, with negative findings. No computed tomographic evidence of injury was noted in the remaining 68 patients (69%), but 1 patient was noted to have a splenic injury while undergoing operative evaluation of the diaphragm. All remaining patients were treated nonoperatively with success. CONCLUSIONS: In patients with anterior abdominal stab wounds, CT should be considered to facilitate initial management decisions, as it has the ability to delineate abnormalities suspicious for injury. PMID- 22036207 TI - Trauma center designation and the decreasing incidence of post-traumatic acute respiratory distress syndrome: a potential guidepost for quality improvement. AB - BACKGROUND: The incidence of post-traumatic acute respiratory distress syndrome (ARDS) is decreasing. We hypothesized that disparities exist in the overall incidence and incidence of ARDS over time across different types of trauma centers. METHODS: The National Trauma Databank version 7.0 was queried for patients admitted to designated trauma centers (I-III) and ventilated at least 48 hours. Level I university admissions (group 1) were compared with level I community and level II/III center admissions (group 2). RESULTS: There were 43,664 patients with an incidence of ARDS of 5.2% (2,260) overall, 4.1% (1,062/25,937) in group 1, and 6.8% (1,198/17,727) in group 2 (P < .001). The incidence decreased significantly in group 1 in contrast to group 2 yearly. The incidence in level I community centers was marked (608/5,180 [11.7%]) and increased significantly over time. On logistic regression, admission to a level I university center (.646 [.590-.707],<.001) was independently associated with ARDS. CONCLUSIONS: Admission to a level I center may not necessarily confer similar results reflecting potential variation in management between centers that presumably provide similar service. These investigations may have significance to quality improvement. PMID- 22036208 TI - Effects of long-term exposure to simazine in real concentrations on common carp (Cyprinus carpio L.). AB - The effects of a 90 day simazine exposure at concentrations of 0.06 (reported concentration in Czech rivers), 1, 2, and 4 MUg L-1 were assessed in one-year-old common carp (Cyprinus carpio L.). Its influence on biometric parameters, hematology, blood biochemistry, liver biomarkers, and histology was investigated. Biometric parameters of common carp exposed to simazine at 0.06 MUg L-1 showed no differences from untreated fish. Simazine concentrations of 1, 2, and 4 MUg L-1 caused significant (p<0.01) increase of hepatosomatic indices relative to controls. Hematological profiles showed significant (p<0.01) decrease in leukocyte count relative to controls at all concentrations. Biochemical profiles of common carp exposed to simazine at all concentrations showed significant (p<0.01) increase in activity of alkaline phosphatase. In addition, at concentrations of 1 and 2 MUg L-1, there was a significant increase in alanine aminotransferase (p<0.05), and, at 4 MUg L-1, a significant increase in total protein (p<0.05), albumins (p<0.05), and alanine aminotransferase (p<0.05) compared with controls. Renal histology revealed severe hyaline degeneration of the epithelial cells of caudal kidney tubules in fish at all exposure levels compared to controls. Chronic exposure of common carp to simazine caused significant shifts in hematological, biochemical, and biometric profiles, and histopathological changes. The results of this study indicate that chronic exposure of simazine has altered multiple physiological indices in fish hematology and biochemistry, which potentially may be a biomarker of simazine toxicity; however, before these parameters are used as special biomarkers for monitoring residual simazine in aquatic environment, more detailed experiments in laboratory need to be performed in the future. PMID- 22036209 TI - Evaluation of tropical water sources and mollusks in southern Brazil using microbiological, biochemical, and chemical parameters. AB - Florianopolis, a city located in the Santa Catarina State in southern Brazil, is the national leading producer of bivalve mollusks. The quality of bivalve mollusks is closely related to the sanitary conditions of surrounding waters where they are cultivated. Presently, cultivation areas receive large amounts of effluents derived mainly from treated and non-treated domestic, rural, and urban sewage. This contributes to the contamination of mollusks with trace metals, pesticides, other organic compounds, and human pathogens such as viruses, bacteria, and protozoan. The aim of this study was to perform a thorough diagnosis of the shellfish growing areas in Florianopolis, on the coast of Santa Catarina. The contamination levels of seawater, sediments, and oysters were evaluated for their microbiological, biochemical, and chemical parameters at five sea sites in Florianopolis, namely three regular oyster cultivation areas (Sites 1, 2, and oyster supplier), a polluted site (Site 3), and a heavily polluted site (Site 4). Samples were evaluated at day zero and after 14 days. Seawater and sediment samples were collected just once, at the end of the experiment. Antioxidant defenses, which may occur in contaminated environments in response to the increased production of reactive oxygen species (ROS) by organisms, were analyzed in oysters, as well as organic compounds (in oysters and sediment samples) and microbiological contamination (in oysters and seawater samples). The results showed the presence of the following contaminants: fecal coliforms in seawater samples (four sites), human adenovirus (all sites), human noroviruses GI and GII (two sites), Hepatitis A viruses (one site), JC Polyomavirus in an oyster sample from the oyster supplier, Giardia duodenalis cysts, and Cryptosporidium sp oocysts (one site). Among organochlorine pesticides, only DDT (dichlorodiphenyltrichloroethane) and HCH (hexachlorocyclohexane) were detected in some sediment and oysters samples in very low levels; site 4 had the highest concentrations of total aliphatic hydrocarbons, PAHs, and linear alkylbenzenes (LABs) found either in oysters or in sediment samples. The major concentration of fecal sterol coprostanol was found at site 4, followed by site 3. After 14 days of allocation in the four selected sites, there was a significant difference in the enzymes analyzed at the monitored spots. The detection of different contaminants in oysters, seawater, and sediment samples in the present study shows the impact untreated or inadequately treated effluents have on coastal areas. These results highlight the need for public investment in adequate wastewater treatment and adequate treatment of oysters, ensuring safe areas for shellfish production as well as healthier bivalve mollusks for consumption. PMID- 22036210 TI - Metabolic and electrochemical mechanisms of dimeric naphthoquinones cytotoxicity in breast cancer cells. AB - Cancer cells reprogram their metabolism due to genetic alteration to compensate for increased energy demand and enhanced anabolism, cell proliferation, and protection from oxidative damage. Here, we assessed the cytotoxicity of three dimeric naphthoquinones against the glycolytic MCF-7 versus the oxidative MDA-453 breast carcinoma cell lines. Dimeric naphthoquinones 1 and 2 impaired MDA-453, but not MCF-7, cell growth at IC(50)=15 MUM. Significant increase in reactive oxygen species, decrease in oxygen consumption and ATP production were observed in MDA-453 cells but not in MCF-7 cell. These findings suggest that oxidative stress and mitochondrial dysfunction are mechanisms by which these agents exert their cytotoxic effects. Cyclic voltammetry and semi-empirical molecular orbital calculations further characterized the electrochemical behavior of these compounds. These results also suggest that dimeric naphthoquinones may be used to selectively target cancer cells that depend on oxidative phosphorylation for energy production and macromolecular synthesis. PMID- 22036211 TI - 1,2-Benzothiazine 1,1-dioxide carboxylate derivatives as novel potent inhibitors of aldose reductase. AB - Due to the importance of aldose reductase (ALR2) as a potential drug target in the treatment of diabetic complications, there are increasing interests in design and synthesis of ALR2 inhibitors. Here, we prepared 1,2-benzothiazine 1,1-dioxide acetic acid derivatives and investigated their inhibition activity. Most of these derivatives were found to be active with IC(50) values ranging from 0.11 MUM to 10.42 MUM, and compound 8d, 2-[2-(4-bromo-2-fluorobenzyl)-1,1-dioxido-2H-1,2 benzothiazin-4(3H)-ylidene]acetic acid, showed the most potent inhibition activity. Further, SAR and docking studies suggest that in comparison with the alpha,beta-unsaturated derivatives, the saturated carboxylic acid derivatives had a greater binding affinity with the enzyme and thus an enhanced inhibition activity. Therefore, development of more powerful ARIs based on benzothiazine 1,1 dioxide by stereo-controlled synthesis could be expected. PMID- 22036212 TI - Synthesis of 6-(het) ary Xylocydine analogues and evaluating their inhibitory activities of CDK1 and CDK2 in vitro. AB - A series of purine nucleoside analogues bearing an aryl and hetaryl group in position 6 were prepared and their biological activities were assessed by in vitro CDK1/Cyclin B1 and CDK2/Cyclin A2 kinase assay. From the synthesized chemicals, three Xylocydine derivatives 3h, 3i, and 3j exhibited specific inhibitory activities on CDK2/Cyclin A2 with IC(50) values of 4.6, 4.8, and 55 MUM, respectively. Those three compounds all induced G1/S phase arrest in Human epithelial carcinoma cell line (HeLa), and the results suggested they may inhibit CDK2 activity in vitro. Furthermore, molecular modeling study, their docking into Cyclin Dependant Kinase 2 (CDK2) active site showed high docking scores. Taken together, these data suggest that, those three compounds are good inhibitors of CDK2 for studying this kinase signal transduction pathway in cell system. PMID- 22036213 TI - Tyrphostin-like compounds with ubiquitin modulatory activity as possible therapeutic agents for multiple myeloma. AB - With the goal of developing small molecules as novel regulators of signal transduction and apoptosis, a series of tyrphostin-like compounds were synthesized and screened for their activity against MM-1 (multiple myeloma) cells and other cell lines representing this malignancy. Synthesis was completed in solution-phase initially and then adopted to solid-phase for generating a more diverse set of compounds. A positive correlation was noted between compounds capable of inducing apoptosis and their modulation of protein ubiquitination. Further analysis suggested that ubiquitin modulation occurs through inhibition of cellular deubiquitinase activity. Bulky groups on the sidechain near the alpha,beta-unsaturated ketone caused a complete loss of activity, whereas cyclization on the opposite side was tolerated. Theoretical calculations at the B3LYP/LACV3P(**) level were completed on each molecule, and the resulting molecular orbitals and Fukui reactivity values for C(beta) carbon were utilized in developing a model to explain the compound activity. PMID- 22036214 TI - A recurrent mutation in the TGM5 gene in European patients with acral peeling skin syndrome. PMID- 22036217 TI - Transcatheter closure of ventricular septal defect and atrial septal defect. PMID- 22036215 TI - Type I interferon signature is high in lupus and neuromyelitis optica but low in multiple sclerosis. AB - OBJECTIVE: Neuromyelitis optica (NMO) is characterized by selective inflammation of the spinal cord and optic nerves but is distinct from multiple sclerosis (MS). Interferon (IFN)-beta mitigates disease activity in MS, but is controversial in NMO, with a few reports of disease worsening after IFN-beta therapy in this highly active disease. In systemic lupus erythematosus (SLE), IFNs adversely affect disease activity. This study examines for the first time whether serum IFN alpha/beta activity and IFN-beta-induced responses in peripheral blood mononuclear cells (MNC) are abnormally elevated in NMO, as they are in SLE, but contrast to low levels in MS. METHODS: Serum type I IFN-alpha/beta activity was measured by a previously validated bioassay of 3 IFN-stimulated genes (RT-PCR sensitivity, 0.1 U/ml) rather than ELISA, which has lower sensitivity and specificity for measuring serum IFNs. IFN responses in PBMNC were assessed by in vitro IFN-beta-induced activation of phospho-tyrosine-STAT1 and phospho-serine STAT1 transcription factors, and MxA proteins using Western blots. RESULTS: Serum IFN-alpha/beta activity was highest in SLE patients, followed by healthy subjects and NMO, but was surprisingly low in therapy-naive MS. In functional assays in vitro, IFN-beta-induced high levels of P-S-STAT1 in NMO and SLE, but not in MS and controls. IFN-beta-induced MxA protein levels were elevated in NMO and SLE compared to MS. CONCLUSIONS: Serum IFN activity and IFN-beta-induced responses in PBMNC are elevated in SLE and NMO patients versus MS. This argues for similarities in pathophysiology between NMO and SLE and provides an explanation for IFN-induced disease worsening in NMO. PMID- 22036218 TI - Neonatal mortality in an urban population in Ibadan, Nigeria. AB - BACKGROUND: Neonatal mortality remains a major contributor to death among children younger than 5 years in developing countries. This study was undertaken to determine the neonatal mortality rate (NMR), causes of death, and associated risk factors among hospital live births in a suburban population in Nigeria. PATIENTS AND METHODS: A total of 1058 consecutive live newborns at Adeoyo Maternity Hospital, Ibadan, were enrolled at birth and followed up in their homes for 28 days. The causes of death were extracted from hospital records, and verbal autopsy was used to determine the causes of death outside the hospital. RESULTS: The NMR was 32.1 per 1000 live births. The leading causes of death were severe perinatal asphyxia (79.4%), low birth weight (LBW: 55.9%), and infections (41.2%). The associated risk factors were lack of antenatal care [relative risk (RR)=45.18; 95% confidence interval (CI)=7.80, 261.60]; prolonged rupture of membranes (RR=4.47; 95% CI=1.95, 10.25); maternal peripartal fever (RR=5.42; 95% CI=2.35, 12.52); prematurity (RR=7.53; 95% CI=4.91, 11.55); and LBW (RR=5.50; 95% CI=3.88, 7.80). CONCLUSION: NMR is high among hospital live births in Ibadan. There is a need for programs encouraging the use of antenatal care, improving skills on neonatal resuscitation and care of LBW infants; as well as implementation of community-based newborn survival strategies. PMID- 22036219 TI - Common etiologies of neonatal pleural effusion. AB - BACKGROUND: Pleural effusion is rare and includes several disease entities in the neonatal period. The aim of this study was to investigate the etiology, management, and outcome of neonatal pleural effusions. METHODS: We retrospectively collected all neonates who were admitted to the neonatal intensive care unit of Chung Shan Medical University Hospital, Taichung, Taiwan, with discharge diagnosis of pleural effusion, chylothorax, hydrothorax, hemothorax, and empyema, from January 1999 to December 2009. The characteristics, etiology, management, and outcome were analyzed. RESULTS: There were 21 patients identified, 16 males (76%) and 5 females (24%). Eight patients (38%) had primary and 13 patients (62%) had secondary etiologies. The etiologies included four parapneumonic effusions or empyema (19%); nine chylothorax (42.8%) with four congenital and five iatrogenic after thoracic surgery; three percutaneously inserted central venous catheter extravasation (14%); one umbilical venous catheter extravasation (4.7%); three hydrops fetalis (14%); and one congestive heart failure (4.7%). Fifteen patients (71%) needed chest tube placement. Conservative management with complete cessation of enteral feedings and use of total parenteral nutrition followed with infant formula containing medium-chain triglyceride was successful in six of the patients (67%) with chylothorax. There were two patients (22%) with chylothorax who received somatostatin administration; one was successful and the other one failed. Thoracic duct ligation was performed uneventfully in two patients with acquired chylothorax. There were three mortalities (14.3%) in this study, which were related to causes other than pleural effusion. CONCLUSIONS: Pleural effusions in the neonatal stage may result from chylothorax, hydrops fetalis, extravasation of percutaneously inserted central venous catheter, parapneumonic effusion, congestive heart failure, or other less frequently occurring conditions. Diagnostic chest tap is required for subsequent management. Good outcome is the rule except in hydrops fetalis, which carries high mortality rate. PMID- 22036220 TI - Color Doppler echocardiographic study on the incidence and natural history of early-infancy muscular ventricular septal defect. AB - BACKGROUND: Most small muscular ventricular septal defect (M-VSD) types have been diagnosed using color Doppler echocardiography. The purpose of this study was to understand the incidence of small M-VSD in the neonatal period and analyze the natural history of these M-VSDs. MATERIALS AND METHODS: All individuals in our study were neonates delivered at term who had a normal healthy appearance. Each accepted neonate had an examination with complete color Doppler echocardiography once before discharge. If the examination was confirmed for M-VSD, the study participants were then classified according to defect type. Further examination was arranged with color Doppler echocardiography at 1 month, 2 months, 4 months, 6 months, 9 months, and 12 months of age or until there was complete spontaneous closure. RESULTS: Among 2891 neonates, we found that 72 (24.9/1000) were diagnosed with M-VSD. Among this group, 38 were male and 34 were female. Only six infants were lost to follow-up. Fifty-four of the 66 infants (81.8%) had M-VSD closed spontaneously at 12 months' follow-up. Significantly, 33 of 37 infants (89.2%) with mid-muscular type, the most common type of M-VSD, closed within the 1(st) year of life compared with apical type (17/24:70.8%). Four of the five infants (80%) had anterior type M-VSD closed. Infants with posterior type M-VSD were not seen during this study period. CONCLUSION: Although the incidence of M VSD was common in the neonatal period, there was also a high rate of spontaneous closure. Therefore, comparison of M-VSD appearance with the incidence of congenital heart disease in neonates had a decisive influence on analysis. PMID- 22036221 TI - Associations of reactive thrombocytosis with clinical characteristics in pediatric diseases. AB - BACKGROUND: Reactive thrombocytosis (RT) in pediatric patients is common, but usually without symptoms. The incidence of RT is different depending on age. Mostly, we reason that RT is a phenomenon, nevertheless the diagnostic value of RT is little known. Therefore, the aim of this study was to determine the association of RT and clinical or laboratory characteristics in pediatric diseases. METHODS: We retrospectively analyzed the medical records of pediatric patients hospitalized at Wan Fang hospital from January 2002 to July 2009. Thrombocytosis was defined as a platelet count more than 500 * 10(9)/L. There were 822 patients enrolled to this study. The clinical parameters, including age, gender, disease type, and hospitalization days, were investigated. The association between RT and clinical manifestations and the relationship of leukocytes, hemoglobin, C-reactive protein, and platelet counts were analyzed. RESULTS: The overall incidence of RT in hospitalized pediatric patients was 6.3%. Infants had a significantly higher incidence (11.3%, p<0.001). Mild RT was found in most patients (83.6%). Infections (75.4%) were the most common cause, followed by perinatal diseases (11.1%). The relationship of RT and age revealed a positive correlation (p=0.045, r=0.70 after adjustment). The degree of RT was an independent factor for hospitalization days (p<0.001, r=0.126 after adjustment). There was a positive correlation between white blood cell count and platelets (p=0.002, r=0.017); on the contrary, the relationship between hemoglobin level and platelets was an inverse correlation (p<0.001, r=-0.193). CONCLUSIONS: In children, the degree of RT was associated with age, and patients had significantly longer hospitalization days in proportion to the increase in platelet count. Laboratory association revealed that the degree of RT was positively correlated to white cell count and negatively correlated to hemoglobin level. Therefore, the degree of RT might be a predictive factor with regard to hospitalization days in pediatric diseases. PMID- 22036222 TI - Cardiac troponin I release after transcatheter atrial septal defect closure correlated with the ratio of the occluder size to body surface area. AB - BACKGROUND: Cardiac troponin I (cTnI) is a very specific and sensitive marker of myocardial injury. The degree of myocardial injury associated with transcatheter atrial septal defect (ASD) closure in children is unknown. METHODS: In a longitudinal study on children with ASD, cTnI serum concentrations were measured after transcatheter ASD closure. Implantation success, complications, and latest patient follow-up were described. RESULTS: We inserted 73 Amplatzer septal occluders in 73 patients. Of these, we excluded two patients in whom the device embolized to the right ventricle the day after deployment. The median age was 4.5 years (range, 1.1-18.0) with 20 boys and 51 girls (male:female ratio, 1:2.6). The mean ASD size was 17 +/- 7 mm, and device size ranged from 7 mm to 38 mm. The Amplatzer size/body surface area ratio was validated by demonstrating positive correlation with cTnI elevation. In children who had a successful attempt, 30 samples had a cTnI value higher than 1.0 MUg/L l at 6 hours after procedure. Six patients had a significant release of cTnI greater than normal limits (mean level of 1.51 +/- 0.26 MUg/L). CONCLUSION: In our study, transcatheter ASD closure induced minor myocardial lesion, the extent of which depended on the ratio of the occluder size to body surface area (p<0.05) but not on the patient's weight or preprocedural left ventricular ejection fraction. PMID- 22036223 TI - Clinical features and treatment responses of children with eosinophilic gastroenteritis. AB - BACKGROUND: Clinical features and treatment responses in pediatric patients with eosinophilic gastroenteritis are rarely reported. This study aimed to evaluate the clinical manifestations and outcome of eosinophilic gastroenteritis in children of Asian background. METHODS: Between 1997 and 2009, 14 Taiwanese patients (nine boys and five girls), with median age of 8.3 years (range, 1.4 14.3 years), were diagnosed with eosinophilic gastroenteritis. The diagnosis was confirmed by the presence of gastrointestinal symptoms, peripheral eosinophilia, and a histology-proved biopsy. The clinical data and responses to medical treatment were analyzed. RESULTS: Initial symptoms included abdominal pain (43%), anemia (36%), hypoalbuminemia (14%), recurrent vomiting (7%), bloody stool (7%), and growth failure (7%). Peripheral eosinophilia was present in 10 patients (71.4%) and positive stool occult blood in seven patients (50%). Endoscopic examination revealed ulcer disease in four patients (28.6%). The treatment included steroid alone, montelukast alone, steroid+montelukast, and steroid+montelukast+ketotifen. Among the patients treated with steroid, two (two of nine, 22%) had successfully tapered off steroid without recurring symptoms. Three patients (three of nine, 33%) had relapses after discontinuing steroid, three (three of nine, 33%) still required low-dose steroid, and one lost to follow-up. There was no relapse in the four patients treated with montelukast alone. CONCLUSIONS: A high percentage of patients presented with gross or occult gastrointestinal bleeding with or without abdominal pain. Endoscopic biopsy is necessary for diagnosis. Steroid was the mainstay treatment for active diseases; montelukast was also effective for the disease or as a maintenance therapy in this study. PMID- 22036224 TI - Left ventricular false tendons: echocardiographic, morphologic, and histopathologic studies and review of the literature. AB - BACKGROUND: Left ventricular false tendons (LVFTs) are fibrous or fibromuscular bands stretching across the left ventricle (LV) from the ventricular septum to the papillary muscle or LV free wall but not connecting, like the chordae tendinae, to the mitral leaflet. LVFTs have become the focus of studies and discussions since the advent of echocardiography. MATERIALS AND METHODS: We prospectively studied the prevalence of LVFTs by two-dimensional echocardiography in 476 infants and children referred to our institute for cardiac evaluation and cardiology workup. We also studied the morphology and histopathology of LVFTs in 68 congenital heart disease specimens and in 20 piglet hearts. The literature was reviewed and the clinical significance of LVFTs was discussed. RESULTS: LVFTs of varying size and different location were detected in 371 (77.9%) of 476 infants and children studied, in 42 (61.8%) of 68 congenital heart disease specimens, and in 19 (95.0%) of 20 piglet hearts. Of the 75 LVFTs from the congenital heart disease specimens, 33 (44.4%) were fibrous type, measuring less than 1.4mm; 38 (50.7%) were fibromuscular type, 1.5-2.4mm; and 4 (5.3%) were muscular type, 2.5mm or more in diameter. Of the 33 LVFTs from the piglet hearts, 23 (69.7%) and 10 (30.3%) were fibrous and fibromuscular, respectively, and none (0.0%) was muscular. CONCLUSIONS: LVFTs were detected partially or completely by modified two-dimensional echocardiography in both normal and abnormal hearts. LVFTs is a useful anatomical landmark of LV for the differentiation of morphological LV and right ventricle in segmental analysis of congenital heart disease. LVFTs are a cause of functional murmur. No pressure gradient was noted in the mid-LV or outflow tract. LVFTs could be a contributory factor in the generation of dysrhythmias during LV catheterization studies. LVFTs were more easily identifiable in neonates and young age patients because of a better delineation of images in echocardiography. PMID- 22036225 TI - Siblings with deletion 22q13.3 and trisomy 15q26 inherited from a maternally balanced translocation. AB - We describe two siblings with generalized hypotonia, expressive language delay, developmental delay, mild facial dysmorphism, and accelerated growth. In addition, the male sibling had testis dysgenesis. Cytogenetic evaluation revealed an unbalanced maternally inherited translocation t(15;22)(q26;q13.3) resulting in partial monosomy 22q and trisomy 15q. The combination of deletion 22q and duplication 15q has not been described previously. PMID- 22036226 TI - Medulloblastoma presenting with pure word deafness: report of one case and review of literature. AB - Pure word deafness (PWD) is a rare disorder characterized by impaired verbal comprehension sparing discrimination and recognition of nonverbal sounds with relatively normal spontaneous speech, writing, and reading comprehension. Etiologies of this syndrome are varied, and there are rare reports about brain tumor with PWD in children. We report a case of medulloblastoma presented with PWD in a 7-year-old girl. She visited our outpatient clinic because of English dictation performance deterioration. PWD was diagnosed by the otolaryngologist after examinations. Posterior fossa tumor and obstructive hydrocephalus were shown in the magnetic resonance imaging of the brain. The diagnosis of medulloblastoma was then made by pathology. PMID- 22036227 TI - Recurrent bacterial meningitis associated with Mondini dysplasia. AB - We reported two cases of recurrent meningitis and both of them had Mondini dysplasia, which provides a link between the brain and inner ear and is associated with cerebrospinal fluid, otorrhea/rhinorrhea, hearing impairment, and recurrent meningitis. Patients who have hearing impairment and recurrent meningitis should be evaluated for the possibility of this congenital dysplasia, and early diagnosis and prompt surgical intervention may prevent further episodes. PMID- 22036228 TI - Congenital chylothorax in a late preterm infant and successful treatment with octreotide. AB - Chylothorax is defined as abnormal accumulation of lymphatic fluid in the pleural space and is a rare condition in neonates. Chylothorax causes respiratory and nutritional problems and a significant mortality rate. Octreotide is a long acting somatostatin analog that can reduce lymphatic fluid production and has been used as a new strategy in the treatment of chylothorax. Here, we report a premature baby with severe bilateral pleural effusion diagnosed by prenatal ultrasound and subsequently confirmed to be congenital chylothorax after birth. This newborn baby was initially treated with bilateral chest tube insertion to relieve severe respiratory distress. However, the chylothorax recurred after a medium-chain-triglyceride-enriched formula was initiated. The accumulation of chylothorax diminished after the administration of octreotide. Therefore, octreotide may allow the patient to avoid invasive procedures, such as reinsertion of chest tubes or surgery. PMID- 22036229 TI - Synthesis of lipophilic dimeric C-7/C-7-linked ciprofloxacin and C-6/C-6-linked levofloxacin derivatives. Versatile in vitro biological evaluations of monomeric and dimeric fluoroquinolone derivatives as potential antitumor, antibacterial or antimycobacterial agents. AB - The synthesis of C-7/C-7-linked ciprofloxacin (CP) and C-6/C-6-linked levofloxacin (LV) derivatives with modulated lipophilicity is described herein. The synthesized compounds, along with the monomeric analogs described previously, were evaluated in vitro for (i) their growth inhibitory effect against five human cancer cell lines, (ii) their antibacterial activity against Gram-positive Staphylococcus aureus and Enterococcus hirae and Gram-negative Escherichia coli and Pseudomonas aeruginosa strains and (iii) their antimycobacterial activity. The most efficient derivatives as antiproliferative agents (C-7/C-7-linked CP 7e and C-6/C-6-linked LV 11f) displayed IC(50) values in the 0.1-8.7 and 0.2-0.7 MUM ranges respectively while IC(50) values for parent CP and LV ranged from 89 to 476 MUM and from 67 to 622 MUM respectively depending on the cell line. A specific antibacterial activity against S. aureus was found for the monomeric and dimeric derivatives of CP. The most efficient derivative against S. aureus (monomeric oxoethyloctanoate CP derivative 3d) displayed MIC <1 nM. Monomeric alkanoyloxymethyl LV esters (9a,c,e,f) and C-6/C-6-linked LV derivatives (11f-h) were the most efficient derivatives as antimycobacterial agents with MIC and IC(50) values in the 2.5-5 MUM and 1.3-<= 2.5 MUM ranges respectively while MIC and IC(50) values for parent LV were 2.5 and 0.8 MUM, respectively. PMID- 22036230 TI - Optimization of cryopreservation procedures for porcine endothelial progenitor cells. AB - Endothelial progenitor cells (EPCs) provide a powerful option for therapeutic use in ischemic diseases. The cell therapy-induced vasculogenesis requires sufficient homogeneous cells, and cryopreservation is a prerequisite for long-term storage and quality assurance of EPCs. The aim of this study was to optimize cryopreservation protocols of EPCs derived from porcine bone marrow. Bone marrow derived mononuclear cells (MNCs) were isolated by density centrifugation and differentiated into EPCs. The first passage EPCs were frozen by using different methodologies, and after cryopreservation the thawed cells were cultured to the fourth passage. The recovery efficiency and functions of these cells were evaluated by determination of cell viability, proliferation and migration. We found the optimal conditions for cryopreservation of EPCs as follows: (i) a cryopreservation medium consisting of 10% dimethylsulphoxide (DMSO) in combination with 50% fetal bovine serum (FBS); (ii) using a controlled freezing rate at 5 degrees C/min; (iii) at an optimal density of 5*106/ml for cryopreserved EPCs; (iv) a storage temperature of -156 degrees C. Under these conditions we demonstrated that EPCs could be stored in mechanical freezer for up to 18 months after cryopreservation without losing their phenotypic characteristics and biological functions. PMID- 22036231 TI - Enhanced production of trehalose in Escherichia coli by homologous expression of otsBA in the presence of the trehalase inhibitor, validamycin A, at high osmolarity. AB - Trehalose production in Escherichia coli DH5alpha was explored by overexpressing otsBA operon encoding trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase. Production and subsequent degradation of trehalose resulted in low production of trehalose in engineered cells overexpressing otsBA, which was primarily due to the concomitant expression of endogenous trehalase. Through an in vitro enzyme assay and flask cultures of engineered cells, trehalase expression was shown to be directly related to the expression of otsBA rather than osmotic stress. Validamycin A effectively inhibited E. coli trehalase and the intracellular accumulation of trehalose was markedly enhanced in the presence of validamycin A at an optimal concentration in the medium. The trehalose production was further increased upon growth in a hypertonic medium in the presence of validamycin A, with most trehalose accumulating as an intracellular product. The highest titer was obtained when otsBA expression was induced by a medium-copy vector, ptrc99A, with 0.5mM of isopropyl beta-d-1 thiogalactopyranoside. Trehalose titer was 1.7 g/L in controlled bioreactor cultures using synthetic M9 medium supplemented with 40 g/L glycerol, 0.1mM validamycin A, and 300 mM NaCl. PMID- 22036232 TI - Pre-ART HIV resistance testing in Africa: are we there yet? PMID- 22036233 TI - Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study. AB - BACKGROUND: The effect of pretreatment HIV-1 drug resistance on the response to first-line combination antiretroviral therapy (ART) in sub-Saharan Africa has not been assessed. We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large prospective cohort. METHODS: HIV-1 infected patients in the PharmAccess African Studies to Evaluate Resistance Monitoring (PASER-M) cohort started non-nucleoside reverse transcriptase inhibitor-based ART at 13 clinical sites in six countries, from 2007 to 2009. We used the International Antiviral Society-USA drug resistance mutation list and the Stanford algorithm to classify participants into three pretreatment drug resistance categories: no pretreatment drug resistance, pretreatment drug resistance with fully active ART prescribed, or pretreatment drug resistance with reduced susceptibility to at least one prescribed drug. We assessed risk factors of virological failure (>=400 copies per mL) and acquired drug resistance after 12 months of ART by use of multilevel logistic regression with multiple imputations for missing data. CD4 cell count increase was estimated with linear mixed models. FINDINGS: Pretreatment drug resistance results were available for 2579 (94%) of 2733 participants; 2404 (93%) had no pretreatment drug resistance, 123 (5%) had pretreatment drug resistance to at least one prescribed drug, and 52 (2%) had pretreatment drug resistance and received fully active ART. Compared with participants without pretreatment drug resistance, the odds ratio (OR) for virological failure (OR 2.13, 95% CI 1.44-3.14; p<0.0001) and acquired drug-resistance (2.30, 1.55-3.40; p<0.0001) was increased in participants with pretreatment drug resistance to at least one prescribed drug, but not in those with pretreatment drug resistance and fully active ART. CD4 count increased less in participants with pretreatment drug resistance than in those without (35 cells per MUL difference after 12 months; 95% CI 13-58; p=0.002). INTERPRETATION: At least three fully active antiretroviral drugs are needed to ensure an optimum response to first-line regimens and to prevent acquisition of drug resistance. Improved access to alternative combinations of antiretroviral drugs in sub-Saharan Africa is warranted. FUNDING: The Netherlands Ministry of Foreign Affairs. PMID- 22036234 TI - [Spanish registry on heart transplantation. 22nd official report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2010)]. AB - INTRODUCTION AND OBJECTIVES: The purpose of this report is to present the results obtained with heart transplantation since this therapeutic modality first began to be used in Spain in May 1984. METHODS: A descriptive analysis was performed of all heart transplantation performed until December 31, 2010. RESULTS: The total number of transplants is 6291. The average clinical profile of the Spanish heart transplant patient in 2010 was that of a 53-year-old male diagnosed with nonrevascularizable ischemic heart disease accompanied by severely depressed ventricular function and poor functional status. The implanted heart was typically from a 39-year-old donor who had died from brain hemorrhage. The average time on the waiting list was 99 days. Mean survival time has progressively increased over the years. Whereas for the overall series, the probability of survival at 1, 5, 10, and 15 years was 78%, 67%, 54%, and 40%, respectively, over the past 5 years the probability of survival at 1 and 5 years was 85% and 73%, respectively. The most frequent cause of death was acute graft failure (16.5%), followed by infection (15.9%), the combination of graft vascular disease and sudden death (13.7%), tumors (11.9%), and acute rejection (7.8%). CONCLUSIONS: The transplantation survival rates obtained in Spain, especially in recent years, position heart transplant as the treatment of choice in irreversible heart failure patients without other established medical or surgical options. PMID- 22036235 TI - [Spanish catheter ablation registry. 10th official report of the Spanish Society of Cardiology Working Group on Electrophysiology and Arrhythmias (2010)]. AB - INTRODUCTION AND OBJECTIVES: The findings of the 2010 Spanish Catheter Ablation Registry are presented. METHODS: Data were collected in two ways: retrospectively using a standardized questionnaire, and prospectively from a central database. Each participating center selected its own preferred method of data collection. RESULTS: Fifty-seven Spanish centers voluntarily contributed data to the survey. A total of 8762 ablation procedures was analyzed, averaging 154 (97) per center. The 3 main conditions treated were atrioventricular nodal reentrant tachycardia (n=2321; 27%), typical atrial flutter (n=1839; 22%), and accessory pathways (n=1738; 20%). Atrial fibrillation was the fourth most common condition treated (n=1309; 15%), and reflects mild growth. The overall success rate was 94%, major complications occurred in 1.7%, and the overall mortality rate was 0.06%. CONCLUSIONS: Data from the 2010 registry show that the number of ablations carried out continued to increase and exceeded 8700 ablations for the second time. In addition, they show, in general, a higher success rate and a lower number of complications. Again, cavotricuspid isthmus ablation for typical atrial flutter was the second most common condition treated. The number of catheter ablations carried out for ventricular arrhythmias in Spain is growing compared to the previous year. PMID- 22036236 TI - [Are new myocardial tracking systems of three-dimensional strain a reality in daily clinical practice?]. PMID- 22036237 TI - [Mitral regurgitation in patients with systolic heart failure: more than a bystander]. PMID- 22036238 TI - Validity for use in research on vascular diseases of the SIDIAP (Information System for the Development of Research in Primary Care): the EMMA study. AB - INTRODUCTION AND OBJECTIVES: Information in primary care databases can be useful in research, but the validity of these data needs to be evaluated. We sought to analyze the validity of the data used in the EMMA study based on data from the Information System for the Development of Research in Primary Care. METHODS: We compared the prevalence of cardiovascular risk factors observed in EMMA hypertension, diabetes, hypercholesterolemia (and its treatments), obesity, and smoking-with equivalent data from the Registre Gironi del Cor (REGICOR), a population-based study that uses standardized methodology, in 2000. We also compared the incidence rates of vascular diseases and its association with these risk factors in a 5-year follow-up. RESULTS: We analyzed data from 34 823 participants included in EMMA and 2540 REGICOR2000 study participants aged 35 to 74. The prevalence of risk factors did not differ significantly between the 2 studies, except for the prevalence of former smokers in men, which was higher in REGICOR2000 (24.7% [95% confidence interval, 23.9%-25.5%] vs 30.1% [95% confidence interval, 27.1%-33.1%]), and the proportion of patients with lipid lowering and antihypertensive therapy, which was higher in EMMA (46.9% vs 32.7% and 8.7% vs 6.3%, respectively). There were no differences between the 2 studies when comparing the incidence of vascular diseases (2.1% in both studies in men and 1.18% [95% confidence interval, 0.7%-1.7%] in REGICOR2000 vs 0.75% [95% confidence interval, 0.64%-0.87%] in EMMA in women) and its association with risk factors. CONCLUSIONS: The prevalence of cardiovascular risk factors and their association with the incidence of vascular disease observed in the EMMA study are consistent with those observed in an epidemiological population-based study with a standardized methodology. PMID- 22036239 TI - [2011 annual summary. Another meeting with our readers]. PMID- 22036240 TI - Left ventricular morphology and diastolic function in severe obesity: current views. PMID- 22036241 TI - Taste disturbance after mastoid surgery: immediate and long-term effects of chorda tympani nerve sacrifice. AB - OBJECTIVE: To determine the immediate and long-term taste effects of chorda tympani nerve sacrifice in patients undergoing open cavity mastoidectomy. DESIGN, SETTING AND PARTICIPANTS: A retrospective, questionnaire survey of patients receiving follow up and aural toilet following open cavity mastoidectomy, over a four-month period. The questionnaire assessed taste disturbance, both immediately post-operative and current. Available surgical records were reviewed for chorda tympani references. RESULTS: Of 57 patients, six had undergone surgery to both ears. Of those who could recall (37/57), 24.3 per cent were aware of taste disturbance immediately after surgery, while 8.7 per cent reported current disturbance (median post-operative interval, 28.5 years; range, one month to 67 years). No bilateral surgery patients were aware of taste disturbance. CONCLUSION: Mastoidectomy consent procedure emphasises the risk of hearing loss and facial nerve injury, yet in open cavity surgery chorda tympani division is almost inevitable. Reassuringly, most post-operative taste disturbance resolves, and most patients are not aware of long-term disturbance. However, a small percentage suffer ongoing taste disturbance; this could be significant for professional chefs and wine-tasters. The risk of taste disturbance should be addressed in the consent procedure. PMID- 22036242 TI - Comparison and critical evaluation of rehabilitation and home-based exercises for treating shoulder stiffness: prospective, multicenter study with 148 cases. AB - INTRODUCTION: The goal of this study was to evaluate the effectiveness of individual exercises performed as classic rehabilitation or a home program on the clinical progression of patients with shoulder stiffness. Based on this information, the secondary goal was to develop a new rehabilitation protocol. PATIENTS AND METHODS: This prospective, comparative series included 148 cases of shoulder stiffness. There were three treatment groups: T1: classic rehabilitation performed below the pain threshold (58 cases); T2: home program with provocation above the pain threshold (59 cases); T3: home program supervised by a physical therapist (31 cases). The execution, pain level and time spent doing each exercise were compiled for each work session - every day for the first 6 weeks, then every week up to 3 months. Clinical (Constant score) and range of motion evaluations were performed at enrollment, week 6 and month 3.Changes were compared between groups; correlation tests were used to analyse the effectiveness of each exercise during each session. RESULTS: Other than physical therapy and balneotherapy, classic rehabilitation exercises had a negative effect on clinical progression during the first 3 to 5 weeks (P<0.05), but this did not hinder the occurrence of a slow, continuous clinical improvement (P<0.05). Home programs led to rapid functional progression with improvement directly related to the number of exercises actually performed (P<0.05), however, pain during the day increased and pain at night decreased. Supervision by a physical therapist helped to optimize the home program, with the same result at week 6, but a better result at month 3 (P<0.05). CONCLUSIONS: Based on the results of this study, a new treatment protocol for shoulder stiffness was proposed that combines an intensive patient home program with a well-informed physical therapist, who progressively adds classic rehabilitation techniques when they provide the best treatment value for each exercise. Patient education is the key to treatment success. PMID- 22036243 TI - Mosaic osteochondral transplantations in the knee joint, midterm results of the SFA multicenter study. AB - INTRODUCTION: There are several possible options to treat focal articular cartilage defects of the knee. The aim of this study was to evaluate the results and prognostic factors cartilage defects of the knee treated by autologous osteochondral mosaicplasty after more than five years of follow-up. PATIENTS AND METHODS: One hundred forty-two cases were included in this retrospective multicenter study. Etiologies included osteochondral fractures (n=79), and osteochondritis dissecans (n=61). Mean age of patients was 31. There was a majority of men (76%). Mean BMI was 25 (range: 21-41). Fifty-three percent of the knees had a history of surgery. Mean delay between the accident and surgery was 2.5 years. Mean area of the defect was 2.29 cm(2) (range: 0.3-12.25 cm(2)). The depth of the defect was 3 or 4 on the ICRS score in 97% of cases. An additional surgical procedure was associated with mosaicplasty in 14% of the cases. The follow-up evaluation was based on the Hughston score, the ICRS score, the IKDC subjective score, and the IKDC radiological score. Evaluation of control MRI was based on a modified MOCART score. RESULTS: The mean follow-up was 96 +/- 28 months. There were complications in 19 patients. Patients were able to begin athletic activities again after a mean 35 weeks. Most patients (81.8%) were satisfied or very satisfied. There was a significant improvement (p<0.001) in the ICRS, IKDC function and Hughston scores at follow-up. The factors for a good prognosis were: male gender, medial femoral condyle defects, osteochondritis dissecans, deep, small defects, and the shortest possible delay to surgery. Obesity, smoking, work-related accidents, the level of sports practiced, the percentage of coverage of the defect, the number of plugs, and associated lesions did not have a statistically significant effect on the functional results in the final follow-up. DISCUSSION: Autologous osteochondral mosaicplasty seems to be a reliable technique in the short and intermediate term. It has the advantage of being less expensive than reconstructive techniques, is a one-step surgical procedure and results in immediate restoration of cartilage surface. Nevertheless, this is a difficult technique, which may result in complications and requires articular harvesting. This technique is limited by the size of the defect to be treated. The primary indication is deep, small defects on the medial femoral condyle. PMID- 22036244 TI - Treatment of knee cartilage defect in 2010. AB - Treatment of knee cartilage defect, a true challenge, should not only reconstruct hyaline cartilage on a long-term basis, but also be able to prevent osteoarthritis. Osteochondral knee lesions occur in either traumatic lesions or in osteochondritis dissecans (OCD). These lesions can involve all the articular surfaces of the knee in its three compartments. In principle, this review article covers symptomatic ICRS grade C or D lesions, depth III and IV, excluding management of superficial lesions, asymptomatic lesions that are often discovered unexpectedly, and kissing lesions, which arise prior to or during osteoarthritis. For clarity sake, the international classifications used are reviewed, for both functional assessment (ICRS and functional IKDC for osteochondral fractures, Hughston for osteochondritis) and morphological lesion evaluations (the ICRS macroscopic evaluation for fractures, the Bedouelle or SOFCOT for osteochondritis, and MOCART for MRI). The therapeutic armamentarium to treat these lesions is vast, but accessibility varies greatly depending on the country and the legislation in effect. Many comparative studies have been conducted, but they are rarely of high scientific quality; the center effect is nearly constant because patients are often referred to certain centers for an expert opinion. The indications defined herein use algorithms that take into account the size of the cartilage defect and the patient's functional needs for cases of fracture and the vitality, stability, and size of the fragment for cases of osteochondritis dissecans. Fractures measuring less than 2 cm(2) are treated with either microfracturing or mosaic osteochondral grafting, between 2 and 4 cm(2) with microfractures covered with a membrane or a culture of second- or third generation chondrocytes, and beyond this size, giant lesions are subject to an exceptional allografting procedure, harvesting from the posterior condyle, or chondrocyte culture on a 3D matrix to restore volume. Cases of stable osteochondritis dissecans with closed articular cartilage can be simply monitored or treated with perforation in cases of questionable vitality. Cases of open joint cartilage are treated with a PLUS fixation if their vitality is preserved; if not, they are treated comparably to osteochondral fractures, with the type of filling depending on the defect size. PMID- 22036245 TI - Pharmacokinetic comparison of a new sustained-release formulation of glimepiride/metformin 1/500 mg combination tablet and a sustained-release formulation of glimepiride/metformin 2/500 mg combination tablet in healthy Korean male volunteers: a randomized, 2-sequence, 2-period, 2-treatment crossover study. AB - BACKGROUND: The combination of glimepiride and metformin is used for glycemic control in patients with diabetes mellitus. A fixed-dose combination of glimepiride/metformin 2/500 mg slow-release (SR) formulation was developed to improve compliance in polymedicated patients. To accommodate the various dosing regimens of glimepiride, a glimepiride/metformin 1/500 mg SR tablet was also developed. OBJECTIVE: The goal of this study was to compare the pharmacokinetic properties of SR fixed-dose combinations of glimepiride/metformin 2/500 mg and the newly developed glimepiride/metformin 1/500 mg formulation to meet the regulatory requirements for marketing in Korea. METHODS: An open-label, randomized, 2-treatment, 2-period, 2-sequence crossover study was conducted with healthy male volunteers. Eligible subjects were randomly assigned to receive a single dose of glimepiride/metformin 1/500 mg SR (test) or glimepiride/metformin 2/500 mg SR (reference) followed by a 1-week washout period and then administration of the alternate treatment. Serial blood samples were collected immediately before and after dosing for 30 hours, and plasma concentrations were determined by using LC-MS/MS with validated methods. Adverse events were assessed by subjects' self-report and interviews addressing general health-related issues. Safety profiles were evaluated throughout the study. RESULTS: Thirty-three subjects were enrolled (mean [SD] age: 27.9 [4.95] years [range, 21-40 years]). Safety profiles were assessed for all 32 subjects who were administered the study drugs, and pharmacokinetic characteristics were evaluated in the 30 subjects who completed the study. The geometric mean ratios (90% CIs) of test to reference for the dose-normalized C(max) and AUC(0-last) of glimepiride were 0.98 (0.90-1.07) and 1.06 (0.98-1.14), respectively. In the case of metformin, the geometric mean ratios (90% CIs) of test to reference for C(max) and AUC(0-last) were 1.06 (0.98 1.15) and 1.04 (0.97-1.12), respectively. Nine adverse events were reported. Among them, loose stool, abdominal pain, and headache were considered to be likely related to the study drug. All reported adverse events were mild in intensity. CONCLUSIONS: Dose-proportional characteristics of glimepiride and comparable pharmacokinetic properties of metformin were observed between the SR fixed-dose combinations of glimepiride/metformin 1/500 mg and 2/500 mg. A single dose of either treatment was well tolerated, and the safety profiles of the 2 treatments were comparable in this small, selected all-male group of healthy Korean volunteers. PMID- 22036246 TI - Efficacy and safety of prandial premixed therapy using insulin lispro mix 50/50 3 times daily compared with progressive titration of insulin lispro mix 75/25 or biphasic insulin aspart 70/30 twice daily in patients with type 2 diabetes mellitus: a randomized, 16-week, open-label study. AB - BACKGROUND: Prandial premixed therapy 3 times daily has been proposed recently for type 2 diabetes mellitus (T2DM) patients who fail to achieve glycemic control with commonly used premixed insulin analogs, insulin lispro mix 75/25 (LM75/25) and biphasic insulin aspart 70/30 (BIAsp70/30) BID. OBJECTIVE: The aim of this work was to compare the efficacy and safety of 3-times daily insulin lispro mix 50/50 (TID group) with progressive titration of twice-daily LM75/25 or BIAsp70/30 (BID group) administered along with metformin in T2DM patients. METHODS: This was an open-label, 16-week, multicenter, randomized, parallel trial. End point glycosylated hemoglobin (HbA(1c)) was the primary efficacy measure; HbA(1c) reduction from baseline to end point, percentage of patients reaching target HbA(1c) (<7.0% and <=6.5%), postprandial blood glucose (BG), and BG excursions after lunch were secondary measures. Safety was evaluated by collecting adverse events. RESULTS: A total of 302 patients with mean (SD) age 57.7 (9.27) years, diabetes duration 11.2 (6.47) years, HbA(1c) 8.5% (1.23), fasting BG 184.0 (53.04) mg/dL, body weight 86.8 (14.79) kg, body mass index 31.7 (4.23) kg/m(2), and daily insulin dose ~48 IU were randomized. No significant difference was observed in end point HbA(1c) between the 2 groups. Seven-point BG profiles showed lower fasting and postbreakfast BG in the BID group but lower postlunch BG in the TID group. Daily insulin dose change was similar in both groups, with more weight gain in the TID group (P = 0.0009). Overall hypoglycemic rates were similar in both groups, but nocturnal hypoglycemia was more frequent in the BID group (P = 0.0063). CONCLUSIONS: In patients with T2DM who have not achieved adequate glycemic control with LM75/25 and BiAsp70/30 BID plus metformin and who are not candidates for basal bolus therapy, switching either to treatment with LM50/50 TID or to progressive titration of premix insulin analogs BID did not produce sufficient evidence of a difference of overall glycemic control between the 2 treatment groups. Short study duration and less intensive dose adjustments might have contributed to these results. PMID- 22036247 TI - Ultrasonic transmission through multiple-sublattice subwavelength holes arrays. AB - The ultrasonic transmission through plates perforated with 2 * 2 or 3 * 3 square array of subwavelength holes per unit cell are studied by numerical simulations. Calculations are obtained by means of a theoretical model under the rigid-solid assumption. It is demonstrated that when the inter-hole distance within the unit cell is reduced, new transmission dips appear resulting from Wood anomalies that have influence on the second and the third order Fabry-Perot peak. When the inter hole distance within the unit cell is reduced, the transmission spectrum of the multiple-sublattice holes arrays tends to the transmission spectrum of a plate perforated with only one hole in the unit cell. PMID- 22036248 TI - Current practices among allergists on writing self-injectable epinephrine prescriptions for immunotherapy patients. PMID- 22036249 TI - Predictors of neonatal production of IFN-gamma and relation to later wheeze. PMID- 22036250 TI - Antimicrobial therapy of urinary tract infections in children. AB - The main objectives in childhood urinary tract infections are rapid recovery from complaints, prevention of urosepsis and infection-related complications as well as the prevention of renal parenchymal damage. Calculated antibiotic therapy should take the local resistance rates of uropathogens into consideration. The current situation of bacterial resistances differs from region to region. In Escherichia coli, resistance rates against cephalosporins, aminoglycosides, nitrofurantoin und chinolones have been relatively low. In contrast, resistance rates against ampicillin have increased over the last 20 years. A similar trend has been observed for TMP/SMX. The choice of appropriate antibiotics, the duration of therapy and the form of application depend on age, severity of clinical symptoms and the presence of complicating factors. In early infancy, a combination of aminoglycoside/ampicillin or ceftazidime/ampicillin is commonly recommended as first-line treatment in pyelonephritis. Pyelonephritis in young infants should always be treated in a paediatric clinic. In later infancy and childhood, an oral third-generation cephalosporin can be used. PMID- 22036251 TI - X-ray microtomography in biology. AB - Progress in high-resolution X-ray microtomography has provided us with a practical approach to determining three-dimensional (3D) structures of opaque samples at micrometer to submicrometer resolution. In this review, we give an introduction to hard X-ray microtomography and its application to the visualization of 3D structures of biological soft tissues. Practical aspects of sample preparation, handling, data collection, 3D reconstruction, and structure analysis are described. Furthermore, different sample contrasting methods are approached in detail. Examples of microtomographic studies are overviewed to present an outline of biological applications of X-ray microtomography. We also provide perspectives of biological microtomography as the convergence of sciences in X-ray optics, biology, and structural analysis. PMID- 22036252 TI - The most accurate approach for intra-articular needle placement in the knee joint: a systematic review. AB - INTRODUCTION: Intra-articular needle placement in the knee joint, such as injection or aspirations, are commonly used for therapeutic, diagnostic, and research purposes. Although several approaches can be used to establish an intra articular injection or aspiration of the knee joint, the accuracy differs per approach. OBJECTIVE: To summarize the evidence concerning the accuracy of different approaches for intra-articular needle placements in the knee. Additionally, to assess whether the accuracy of different approaches is related to factors such as underlying disease, severity of underlying disease, approach related factors, and/or the rate of local reactions. METHODS: The literature was systemically reviewed until July 2010. Risk of bias of the included studies was assessed by the QUADAS tool. Study characteristics were extracted; accuracy results were pooled per approach. RESULTS: Nine studies were included. The superolateral approach with the leg in extension was studied most (230 injections) and resulted in the highest pooled accuracy of 91% (95% CI 84-99%). The lateral midpatellar approach, the anterolateral approach, and the anteromedial approach resulted in the lowest pooled accuracy rates, 85% (95% CI 68-100%), 67% (95% CI 43-91%) and 72% (95% CI 65-78%), respectively. CONCLUSIONS: The superolateral approach was investigated most and resulted in the highest pooled accuracy rate of 91% (95% CI 84-99%). Nevertheless, this approach still results in a substantial amount of extra-articular needle placements. Guidance of intra-articular needle placements by imaging techniques may enhance the accuracy. The costs and extra time associated with these techniques should be taken into consideration. PMID- 22036254 TI - Interview with Professor George D. Kitas, Chair of Excellence in Rheumatology. PMID- 22036258 TI - Influence of size disparity of transplanted hearts on cardiac growth in infants and children. AB - OBJECTIVE: We aimed to evaluate the influence of size disparity of the transplanted heart on cardiac growth in infant and child recipients by comparing donor body surface area (BSA) and cardiac dimensions during transplantation to the corresponding parameters of the recipient over a period of time. METHODS: A retrospective review of medical and echocardiographic records of 147 children (5.3 +/- 4.0; median, 4.1; range, 1 month-15 years) who underwent orthotopic heart transplantation was done. The patients were divided into age groups as follows: less than 1 year (n = 23), 1 to 2 years (n = 26), more than 2 to 5 years (n = 18), more than 5 to 10 years (n = 27), and more than 10 to 15 years (n = 53). Donor/recipient BSA ratio was determined during transplantation. Cardiac dimensions were measured 30 days after transplantation and compared at 1 year, 2 to 5 years, and 5 to 10 years after transplantation. RESULTS: There were no significant differences in the ventricular end-diastolic diameter, volumes, and mass among those with a donor/recipient BSA ratio of less than 0.80, 0.8 to 1.2, and more than 1.2 (P = .80, .44, and .48, respectively). In all the cardiac dimensions and volumes measured, donor-recipient mismatch did not influence the continuous growth of the heart, as indicated by the measured parameters, in accordance with the recipients' increase in BSA over time. All calculated Z scores at 1 year, 2 to 5 years, and 6 to 10 years after transplantation were normal when indexed to BSA. CONCLUSIONS: This study demonstrates that despite size disparity of a transplanted heart, it undergoes normal growth in diastolic dimensions, volumes, and myocardial mass over time as appropriate for body growth after cardiac transplantation in infants and children. PMID- 22036259 TI - Off-pump coronary artery bypass grafting does not preserve renal function better than on-pump coronary artery bypass grafting: results of a case-matched study. AB - OBJECTIVE: Controversy exists regarding the perioperative renal effects of off pump versus on-pump coronary artery bypass grafting. Large case-matched and randomized comparisons have shown conflicting results. This study focuses on this clinical controversy. METHODS: We studied 5589 consecutive patients from a single center who underwent off-pump or on-pump coronary artery bypass grafting between 2002 and 2010. All preoperative, intraoperative, and postoperative data were prospectively collected. Patients were matched by using a nearest neighbor matching estimation method for average treatment effects, with bias correction (Stata 11.2, StataCorp, College Station, Tex). The matching characteristics were age, gender, body mass index, hypertension, diabetes, peripheral vascular disease, cerebrovascular disease, left ventricular grade, preoperative serum creatinine, operative priority, and Cardiac Anesthesia Risk Evaluation score. RESULTS: The mean patient age was 64.9 +/- 10.0 years, and 4387 (78.5%) were male. Mean calculated preoperative creatinine clearance was 82.0 +/- 32.6 mL/min. Perioperative mortality was 1.5% with off-pump coronary artery bypass grafting and 1.7% with on-pump coronary artery bypass grafting (P = .6). The mean change in creatinine clearance, from the preoperative value to the lowest postoperative value, was -6.3 +/- 14.1 mL/min with off-pump coronary artery bypass grafting versus -5.0 +/- 15.5 mL/min with on-pump coronary artery bypass grafting (P = .06). After matching, patients undergoing off-pump coronary artery bypass grafting had a greater creatinine increase and greater loss of creatinine clearance postoperatively compared with patients undergoing on-pump coronary artery bypass grafting (both P < .05). Requirements for de novo postoperative dialysis were equivalent at 2.6% in off-pump coronary artery bypass grafting versus 2.1% in on-pump coronary artery bypass grafting (P = .4). Median postoperative hospital stay was 8 days in both groups (P = .8). CONCLUSIONS: Off pump coronary artery bypass grafting does not preserve renal function to a greater extent than on-pump coronary artery bypass grafting. In fact, a trend to the reverse exists with no clinically harmful effects. PMID- 22036260 TI - Predictive value of near-infrared spectroscopy on neurodevelopmental outcome after surgery for congenital heart disease in infancy. AB - OBJECTIVE: To explore the relationship between intraoperative regional cerebral oxygen saturation (rSO(2)) measured by near-infrared spectroscopy (NIRS) and neurodevelopmental outcome in children after cardiac surgery. METHODS: Cross sectional neurodevelopmental evaluation at 2 years of age was performed in a cohort of young infants who had surgery for congenital heart disease in 2007. The third edition of Bayley Scales of Infant and Toddler Development (Bayley-III) was used to assess cognitive, language, and motor functioning. Clinical and perioperative data were collected, including intraoperative rSO(2) nadir, rSO(2) percent decrease from baseline, and cumulative minutes of at least 20%, 30%, and 40% decrease from baseline. RESULTS: Twenty-seven patients without chromosomal abnormality were included in analyses. Mean Bayley-III scores fell within 1 standard deviation of the normative mean. Stepwise regression analyses of patient and procedure-related variables, including rSO(2), demonstrated that cognitive ability was predicted by length of hospital stay and premature birth (58.1% of variance), receptive communication was predicted by length of hospital stay and rSO(2) nadir (40.2% of variance), expressive communication was predicted by birth weight (26.2% of variance), fine motor functioning was predicted by duration of cardiac intensive care unit stay (41.4% of variance), and gross motor functioning was predicted by the presence of a significant comorbidity (43.5% of variance). CONCLUSIONS: In a contemporary cohort of infants undergoing surgery for congenital heart disease, neurodevelopmental outcomes at 2 years of age are largely influenced by patient-related characteristics. Although receptive communication appears to be influenced by rSO(2) nadir, the predictive value of NIRS remains unclear. PMID- 22036261 TI - A heart team's perspective on interventional mitral valve repair: percutaneous clip implantation as an important adjunct to a surgical mitral valve program for treatment of high-risk patients. AB - OBJECTIVE: Surgical mitral valve repair carries an elevated perioperative risk in the presence of severely reduced ventricular function and relevant comorbidities. We sought to assess the feasibility of catheter-based mitral valve repair using a clip-based percutaneous edge-to-edge repair system in selected patients at high surgical risk with mitral regurgitation grade 3 or worse. METHODS: Between 2002 and January 2011, 202 consecutive patients without prior mitral valve surgery (age 75 +/- 9 years; 63% were male) with symptomatic functional (65%), degenerative (27%), or mixed (8%) mitral regurgitation were treated with a percutaneous clip system for approximation of the anterior and posterior mitral leaflets. Risk for mitral valve surgery was considered high in terms of a mean logistic European System for Cardiac Operative Risk Evaluation of 44% (range, 21% 54%). Preprocedural left ventricular ejection fraction was 35% or less in 36% of patients. An interdisciplinary heart team of cardiologists and cardiac surgeons discussed all patients. RESULTS: Percutaneous clip implantation was successful in 186 patients (92%). Patients were treated with 1 clip (n = 125; 62%), 2 clips (n = 64; 32%), or 3 or more clips (n = 7; 3%). Reduction in mitral regurgitation from pre- to postprocedure was significant (P < .0001) and remained stable within the first 12 months in the majority of patients. Thirty-day mortality was 3.5% (7/202 patients). Hospital stay was 12 +/- 10 days, and median intensive care unit stay was 1 day (range, 0-45 days). Eleven patients required surgical valve repair/replacement at a median of 38 days (0-468 days) after percutaneous clip implantation. CONCLUSIONS: Clip-based percutaneous mitral valve repair is a safe, low-risk, and effective therapeutic option in symptomatic patients with a high risk for surgery and does not exclude later surgical repair. PMID- 22036264 TI - Accumulation and phytotoxicity of microcystin-LR in rice (Oryza sativa). AB - Irrigation with eutrophic water containing microcystins-LR (MC-LR) poses a potential risk to crops. However, the accumulation of MC-LR in rice grains and the mechanism of MC-LR-induced inhibition in rice roots are not understood. In this study, we detected the accumulation of MC-LR in rice grains collected from Taihu Lake region. MC-LR could accumulate in rice grains, but the risk evaluation suggested that MC-LR levels in rice grains from Taihu Lake region may not pose a threat to human health currently. In addition, MC-LR with low concentrations did not affect the growth of rice roots. However, MC-LR with high concentrations impeded the rice root morphogenesis by inhibiting root elongation, crown root formation, and lateral root development from primordia. Treatment with high concentrations of MC-LR stimulated the production of reactive oxygen species (ROS) and inhibited the production of nitric oxide (NO) in rice roots. Exogenous NO treatment reversed the inhibition of rice root growth under MC-LR stress. These results indicated that ROS and NO played important roles in the development of rice roots in responding to MC-LR stress. PMID- 22036265 TI - Molecular profiling of marine fauna: integration of omics with environmental assessment of the world's oceans. AB - Many species that contribute to the commercial and ecological richness of our marine ecosystems are harbingers of environmental change. The ability of organisms to rapidly detect and respond to changes in the surrounding environment represents the foundation for application of molecular profiling technologies towards marine sentinel species in an attempt to identify signature profiles that may reside within the transcriptome, proteome, or metabolome and that are indicative of a particular environmental exposure event. The current review highlights recent examples of the biological information obtained for marine sentinel teleosts, mammals, and invertebrates. While in its infancy, such basal information can provide a systems biology framework in the detection and evaluation of environmental chemical contaminant effects on marine fauna. Repeated evaluation across different seasons and local marine environs will lead to discrimination between signature profiles representing normal variation within the complex milieu of environmental factors that trigger biological response in a given sentinel species and permit a greater understanding of normal versus anthropogenic-associated modulation of biological pathways, which prove detrimental to marine fauna. It is anticipated that incorporation of contaminant specific molecular signatures into current risk assessment paradigms will lead to enhanced wildlife management strategies that minimize the impacts of our industrialized society on marine ecosystems. PMID- 22036266 TI - Adverse effects of bisphenol A on reproductive physiology in male goldfish at environmentally relevant concentrations. AB - Alternations of reproductive physiology were studied in the male goldfish (Carassius auratus L.) exposed to environmentally relevant concentrations (0.6, 4.5 and 11.0 MUg/L) of bisphenol A (BPA) at days 10, 20 and 30 after exposure. Significant effects of BPA concentration, exposure time and their interactions were observed on testosterone (T), 11-ketotestosterone (11-KT) and sperm motility and velocity, but gonadosomatic index (GSI), hepatosomatic index (HSI) and 17beta estradiol (E(2)) were not affected. Vitellogenin (VTG) was only affected by BPA concentration. The T and 11-KT levels were significantly decreased in the BPA treated groups after 20 or 30 days. Sperm motility was significantly decreased at 15, 30, 60 and 90 s post-activation in the BPA-treated groups after 20 or 30 days. But, significant decrease in sperm velocity was observed at 30, 60 and 90 s post-activation in the BPA-treated groups at all exposure times. The VTG was significantly increased in the males exposed to 11.0 MUg/L at day 30 after exposure. The GSI, HSI and E(2) did not differ between the BPA-treated groups and control. The present study shows that the decrease of sperm quality is concurrent with the decrease of androgens and increase of VTG. The results suggest adverse effects of BPA on sperm motility and velocity via modifications of testicular steroidogenesis that might correspond to alternation in sperm maturation. PMID- 22036267 TI - Altered transfer of heavy metals from soil to Chinese cabbage with film mulching. AB - The influence of film mulching on the migration of metals from soil to cabbage was investigated. Following a 50-day growth in field plots mulched or unmulched, root-zone soils and Chinese cabbage (Brassica chinensis L.) were sampled for metal analysis. Mulching slightly decreased the soil mobile (acid-extractable) Cd, but increased its transfer from root to the cabbage parts. As an essential element, Cu was readily transferred to the cabbage parts. While mulching decreased the soil mobile Zn, reduced soil pH resulted in its enhanced soil-to root migration. This, however, did not increase the transfer of Zn within cabbage. Although mulching increased the soil mobile Pb by 200%, an increase in Pb in cabbage leaves but a decrease in stem result presumably from the enhanced foliar uptake of atmospheric Pb. This study suggests that mulching may promote the accumulation of toxic metals such as Cd and Pb in cabbage and therefore increase crop risks to human health. PMID- 22036268 TI - The anti-microbial peptide LL-37 modulates immune responses in the palatine tonsils where it is exclusively expressed by neutrophils and a subset of dendritic cells. AB - Antimicrobial peptides are essential elements of epithelial defense against invading micro-organisms. The palatine tonsils are positioned at the entry of the airway and the gut and as such are ideally situated to act as immune sentinels in the pharynx protecting against microbial invasion. Tonsils express a number of antimicrobial peptides including hCAP18/LL-37. Here we clearly define the expression of hCAP18/LL-37 in the tonsils showing unequivocally that hCAP18/LL-37 is mainly expressed by infiltrating neutrophils and follicular CD11c+CD13+HLA-DR+ dendritic cells, rarely by macrophages, and never by the epithelium itself. To explore possible functions for follicle-derived LL-37, we stimulated tonsil mononuclear cells with LL-37 in vitro and observed the secretion of the proinflammatory cytokines CCL5 and CXCL9, expression of IFN-gamma and MX-1 and down-regulation of chemokine receptors CCR4 and CCR6 which are involved in tissue selective T cell trafficking. Taken together, these data illustrate new potential immunoregulatory functions for hCAP18/LL-37 in the tonsils. PMID- 22036269 TI - Immunomodulatory effects of extracorporeal photochemotherapy in systemic sclerosis. AB - The aim of this study was to evaluate the clinical and immunomodulatory effects of extracorporeal photochemotherapy (ECP) in systemic sclerosis (SSc). We enrolled 16 patients with diffuse cutaneous SSc, who received 12 ECP treatments in total. After ECP treatments, the dermal thickness reduced and the mobility of joints improved. Internal organ involvement did not deteriorate. The percentages and numbers of peripheral Th17 cells decreased, the values of Tr1 and Treg cells increased, and the suppressor capacity of Treg cells improved. Interestingly, we found a positive correlation between the reduction of IL-17 levels and skin thickness measured by ultrasound. Moreover, levels of CCL2 and TGF-beta decreased, while the concentration of IL-1Ra, IL-10 and HGF elevated during the therapy. ECP treatments contribute to the restoration of disproportional autoimmune responses and attenuate fibrotic processes, thus decelerate the disease progression. Accordingly, ECP can be a useful element of novel treatment modalities proposed for SSc. PMID- 22036270 TI - Involving people with learning disabilities in nurse education: towards an inclusive approach. AB - There is limited evidence that explores how to effectively include people with learning disabilities in nurse education in the U.K. The majority of reported work relates to mental health nursing and social work training (Morgan and Jones, 2009). This paper specifically reports on the processes and activities undertaken by the authors with people with learning disabilities in the development of a new BSc learning disability nursing programme, a specific branch of nursing in the U.K. In doing so, findings and discussion from two separate projects involving students and people with learning disabilities will be integrated into the paper. EPICURE (Engagement, Processing, Interpretation, Critique, Usefulness, Relevance and Ethics (Stige et al. 2009) is adopted as a qualitative framework throughout the paper to evaluate the reported work that took place between September 2006 and October 2010. Suggestions are therefore made regarding the benefits and challenges of striving towards an inclusive approach to user involvement in nurse education, with particular reference to learning disability. The work presented in the paper demonstrates how through careful involvement of this population, deeper learning opportunities for all nursing students can be created. PMID- 22036271 TI - Developing a service user facilitated, interactive case study--a reflective and evaluative account of a teaching method. AB - This article describes the development and ongoing evaluation of a method of service user facilitated case study in health and social care education in a U.K. University. An action research approach (Norton 2009) has been used in which the aim of the work is to improve personal practice with the aim of enhancing the student experience. The paper is written from the perspective of the service user with support from an academic colleague. The paper describes how a narrative monologue, over time is developed into an interactive case study. In draws upon literature from service user involvement, case study and pedagogic action research. The research group are health and social care students both under and post-graduates. Analysis is via a session evaluation form. Thematic analysis draws out key themes. Firstly that first person accounts have a reasonance and interest with students. Secondly that the built in thinking time helps students to develop their reflection and critical thinking skills. Furthermore a theme emerges on how the technique supports students with their future careers. Finally the author reflects on how the approach enables the development of teaching practice and enhanced student learning. PMID- 22036272 TI - Promoting information literacy through collaborative service learning in an undergraduate research course. AB - Information literacy is an important foundation for evidence-based nursing practice. Librarians, the experts in information literacy, are important collaborators in the process of teaching nursing students information literacy skills. In this article we describe a service learning project, offered in a third year nursing research course, designed to teach information literacy and to enhance students' appreciation of the role of evidence in nursing practice. Students worked in groups, and under the guidance of a nursing instructor and librarian, to answer a question posed by practice-based partners. Through the project students learned essential skills of refining a question, identifying systematic search strategies, gleaning essential information from a study and using a bibliographic management tool. Evaluation of the project indicated that although the project was challenging and labour intensive students felt they learned important skills for their future practice. Several recommendations for further enhancing the collaboration are made. PMID- 22036273 TI - Effect of a video on developing skills in undergraduate nursing students for the management of totally implantable central venous access ports. AB - BACKGROUND: Handling Totally Implantable Access Ports (TIAP) is a nursing procedure that requires skill and knowledge to avoid adverse events. No studies addressing this procedure with undergraduate students were identified prior to this study. Communication technologies, such as videos, have been increasingly adopted in the teaching of nursing and have contributed to the acquisition of competencies for clinical performance. OBJECTIVE: To evaluate the effect of a video on the puncture and heparinization of TIAP in the development of cognitive and technical competencies of undergraduate nursing students. METHOD: Quasi experimental study with a pretest-posttest design. RESULTS: 24 individuals participated in the study. Anxiety scores were kept at levels 1 and 2 in the pretest and posttest. In relation to cognitive knowledge concerning the procedure, the proportion of correct answers in the pretest was 0.14 (SD=0.12) and 0.90 in the posttest (SD=0.05). After watching the video, the average score obtained by the participants in the mock session was 27.20. CONCLUSION: The use of an educational video with a simulation of puncture and heparinization of TIAP proved to be a strategy that increased both cognitive and technical knowledge. This strategy is viable in the teaching-learning process and is useful as a support tool for professors and for the development of undergraduate nursing students. PMID- 22036274 TI - Ligament reconstruction of the Trapezial-metacarpal joint for early arthritis: a preliminary report. AB - PURPOSE: To evaluate the results and determine the efficacy of an alternative ligament reconstruction technique in patients with a symptomatic trapezial metacarpal joint associated with subluxation and early or limited chondral damage. METHODS: This retrospective, nonrandomized study was composed of 6 patients, all women with ages between 31-46 years, treated by arthroscopic evaluation and reconstruction of the intermetacarpal and reverse anterior oblique ligament of the trapezial-metacarpal joint, using a strip of flexor carpi radialis tendon. Evaluation at an average follow-up of 18 months (range,12-28 mo) consisted of interview, examination, and computed tomography. RESULTS: The visual analog pain score, preoperative rest pain, and activity pain improved significantly after surgery. Tip and lateral pinch strength measured 92% compared to the contralateral thumb, and computed tomography showed improved alignment of all joints. CONCLUSIONS: Our results indicate that ligament reconstruction using the technique described reduced pain, increased strength, and improved the trapezial-metacarpal joint alignment in patients with early symptomatic trapezial metacarpal joint osteoarthritis associated with joint subluxation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 22036275 TI - Incidence of scaphotrapezial arthritis following volar percutaneous fixation of nondisplaced scaphoid waist fractures using a transtrapezial approach. AB - PURPOSE: To investigate whether volar percutaneous screw fixation of scaphoid waist fractures via a transtrapezial approach causes degenerative changes at the scaphotrapezial (ST) joint at short- to medium-term follow-up. METHODS: A total of 34 patients were available for follow-up at a mean of 6.1 years (minimum follow-up, 3.7 y) after volar percutaneous fixation of acute scaphoid waist fractures via a transtrapezial approach. The clinical follow-up examination included assessment of pain using a visual analog scale, range of motion, grip strength, and key pinch strength. We obtained radiographs of both hands in 3 views. We staged degenerative changes at the ST joint according to the modified Eaton and Glickel classification. RESULTS: The modified Mayo wrist score showed excellent clinical results using the described technique. One patient showed asymptomatic unilateral stage 2 osteoarthritic changes at the ST joint. We noted 6 screw protrusions, which required screw removal in 2 patients, in the early stages of use of the transtrapezial technique. One patient was treated surgically for a bone cyst. CONCLUSIONS: Volar percutaneous screw fixation of nondisplaced scaphoid waist fractures using a transtrapezial approach does not lead to symptomatic scaphotrapezial osteoarthritis at short- to medium-term follow-up. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 22036276 TI - Surgical versus nonsurgical treatment of acute minimally displaced and undisplaced scaphoid waist fractures: pairwise and network meta-analyses of randomized controlled trials. AB - PURPOSE: To investigate the effectiveness of surgical treatment for minimally displaced and undisplaced scaphoid waist fractures compared with nonsurgical intervention through pairwise and network meta-analyses of randomized controlled trials. METHODS: We searched several databases from 1990 to 2009 for randomized controlled trials that evaluated surgical and nonsurgical treatments of undisplaced or minimally displaced scaphoid waist fractures. We based the main pairwise meta-analysis comparison on the odds ratio of fracture union between patients undergoing surgical versus nonsurgical treatment. We also investigated other outcome measures including complications, range of motion, grip strength, and osteoarthritis of the scaphotrapeziotrapezoid and radiocarpal joints. We used a network meta-analysis to simultaneously synthesize trials making different intervention comparisons while modeling different surgical and nonsurgical treatments distinctly. RESULTS: Of the 67 articles identified, 6 studies were eligible for the primary pairwise meta-analysis, with a total of 363 patients. The pooled odds ratio of fracture union between the surgical and nonsurgical groups was in favor of surgery but not statistically significant. Surgical treatment was associated with a statistically significant elevated risk of complication. Range of motion, grip strength, and osteoarthritis of the scaphotrapeziotrapezoid and radiocarpal joints did not reach statistical significance in the pairwise meta-analyses. The mixed-treatment network meta analysis showed that open (Herbert) screw fixation had a probability of 0.73 as being the best treatment method compared with percutaneous screw fixation, short arm cast, and short thumb spica cast. CONCLUSIONS: Although surgical treatment is favored in terms of fracture union in our pairwise meta-analysis, this did not reach statistical significance, but was associated with a significantly increased risk of complications. The cumulative evidence at present does not support routine surgical treatment, and aggressive conservative management should remain the mainstay for scaphoid waist fractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I. PMID- 22036277 TI - Foreign-body reaction and osteolysis induced by an intraosseous poly-L-lactic Acid suture anchor in the wrist: case report. AB - Polyglycolic acid and poly-L-lactic acid have become popular choices for bioabsorbable anchor fixation in the hand and wrist. We report a case of osteolysis, synovitis, and chondral erosion secondary to a poly-L-lactic acid suture anchor in the wrist. PMID- 22036278 TI - Subluxation of the distal radioulnar joint as a predictor of foveal triangular fibrocartilage complex tears. AB - PURPOSE: The triangular fibrocartilage complex (TFCC) with its ulnar foveal attachment is the primary stabilizer of the distal radioulnar joint (DRUJ). The purpose of this study was to describe a technique for measuring the degree of subluxation of the DRUJ in wrist magnetic resonance imaging (MRI) examinations to predict tears involving the foveal attachment of the TFCC. METHODS: We measured DRUJ geometry in wrist MRI examinations of 34 patients who were found to have foveal TFCC tears at surgery. We compared the results with DRUJ geometry in 11 asymptomatic controls. Subluxation of the ulnar head was assessed using transaxial MRI images obtained at the level of the DRUJ with the wrist in pronation. We quantified subluxation with a line spanning the sigmoid notch of the radius and a perpendicular line through the center of curvature of the articulating surface of the ulna. We calculated the ratio of the lengths of the dorsal and volar segments and normalized it to the center of the sigmoid notch. RESULTS: A total of 34 patients with intraoperatively confirmed tears of the foveal attachment of the TFCC had a mean dorsal ulnar subluxation measurement of 16% +/- 4%, whereas the 11 controls had a mean subluxation measurement of 5% +/- 4%. CONCLUSIONS: The results confirm the hypothesis that subluxation of the ulnar head relative to the sigmoid notch of the radius, as assessed by MRI with the wrist in pronation, is a predictor of tears of the foveal attachment of the TFCC. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II. PMID- 22036279 TI - Effect of distal radius volar plate position on contact pressure between the flexor pollicis longus tendon and the distal plate edge. AB - PURPOSE: Some clinical studies have suggested that distal radius plates placed distal to the watershed line have the potential to impinge on the traversing flexor tendons. However, the validity of this theory remains unclear. The purpose of this study was to evaluate the quantitative effect of volar plate position on flexor pollicis longus (FPL) tendon friction by measuring the contact pressure between the FPL tendon and the distal edge of the locking plate. METHODS: We used 7 fresh cadaveric upper extremities without wrist osteoarthritis or any deformity. External loads of 1.5 and 3.0 kgf were applied to the FPL tendon to simulate the pinch function of the thumb. A distal radius volar plate was applied to these cadaveric specimens in various positions relative to the watershed line. We measured contact pressure between the distal plate edge and the FPL tendon using a thin flexible pressure sensor and compared it among various positions of the volar plate for wrist extension angles of 0 degrees , 30 degrees , and 60 degrees and ulnar deviation angles of 0 degrees and 20 degrees . RESULTS: Under the 30 degrees or 60 degrees wrist extension condition, contact pressure significantly increased when the distal plate edge was placed distal to the watershed line, compared with when it was placed proximal to or at the watershed line. CONCLUSIONS: Our quantitative results support the theory that plates placed distal to the watershed line have the potential to impinge on the traversing FPL tendon, even when a radius fracture heals anatomically. CLINICAL RELEVANCE: This study clarifies a mechanism of FPL tendon irritation after volar plate fixation for distal radius fractures. PMID- 22036280 TI - The role of bone allografts in the treatment of angular malunions of the distal radius. AB - PURPOSE: Two cohorts of patients who had corrective osteotomies and volar platings for malunited fractures of the distal radius were compared retrospectively to determine whether the time to union and the outcome were affected by bone allograft. METHODS: Patients in the first group (n = 14) did not receive any bone graft; patients in the second group (n = 14) had allograft bone chips following volar plating. Indications for surgery, surgical technique, and postoperative rehabilitation were the same in both groups. Volar cortical contact was maintained using a volar locking plate in all patients. Radiographic parameters of deformity correction, time to union, wrist and forearm range of motion, grip strength, patient-rated wrist evaluation and Disabilities of the Arm, Shoulder, and Hand questionnaire were used to evaluate the outcome before and after the surgery. Average follow-up time was 36 weeks. Patients who had diabetes, who smoked, who had a body mass index of more than 35, and who required lengthening for deformity correction were excluded from the study. RESULTS: Osteotomies in both groups healed without loss of surgical correction. Final outcome and time to union revealed no significant differences, clinically or statistically, between the 2 groups. The Disabilities of the Arm, Shoulder, and Hand score was improved in both groups. CONCLUSIONS: When volar cortical contact was maintained using a volar locked plate, bone allograft at the osteotomy site did not improve the final outcome. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 22036281 TI - Trends in wrist fractures in children and adolescents, 1997-2009. AB - PURPOSE: Distal radius and carpal fractures in children and adolescents represent approximately 25% of all pediatric fractures. Incidence rates and causes of these fractures change over time owing to changes in activities and risk factors. The purpose of this study was to examine recent population-based trends in incidence and causes of wrist fractures in children and adolescents. METHODS: We obtained data from the Dutch Injury Surveillance System of emergency department visits of 15 geographically distributed hospitals, and from the National Hospital Discharge Registry. This included a representative sample of outpatients and inpatients, respectively. We calculated incidence rates of wrist fractures per 100,000 person years for each year between 1997 and 2009. Using Poisson's regression, we analyzed trends for children and adolescents 5 to 9, 10 to 14, and 15 to 19 years of age separately for boys and girls. RESULTS: During the study period, incidence rates increased significantly in boys and girls 5 to 9 and 10 to 14 years of age, with the strongest increase in the age group 10 to 14 years. The observed increases were mainly due to increased incidence rates during soccer and gymnastics at school. CONCLUSIONS: This population-based study revealed a substantial sports-related increase in the incidence rate of wrist fractures in boys and girls aged 5 to 9 and 10 to 14 years in the period 1997 to 2009. CLINICAL RELEVANCE: With knowledge of the epidemiology of wrist fractures, prevention programs can be improved. From this study, we know that the incidence rate of wrist fractures in childhood is increasing, mainly as a result of soccer and gymnastics at school. Future sport injury research and surveillance data are necessary to develop new prevention programs based on identifying and addressing specific risk factors, especially in young athletes. PMID- 22036282 TI - Oculodentodigital dysplasia: ulnar-sided syndactyly and its associated disorders. AB - PURPOSE: Hand surgeons are often the first specialists to see patients with oculodentodigital dysplasia (ODDD), when infants with ulnar-sided syndactyly are referred. Major associated problems include neurologic, ophthalmologic, dental, and other skeletal abnormalities. The purposes of this study were to investigate the incidence of the reported associated conditions in the families of our patients with ODDD, correlate them with the severity of syndactyly, and provide better counseling with more accurate information for these patients and families. METHODS: We reviewed medical records from Texas Scottish Rite Hospital for Children from 1980 to 2009 to identify patients with ODDD. These patients and families were invited to return for a detailed medical and family history and physical examination documenting hand, foot, eye, dental, and facial findings. RESULTS: A total of 73 pediatric patients from 47 families were diagnosed with ODDD, and 38 individuals in 31 families agreed to participate in the study. We observed bilateral syndactyly in 32 patients, with symmetric involvement in 31 of these. Abnormalities of the shape and size of the middle phalanx of the small finger were common. Ophthalmological findings were present in 31 and dental abnormalities identified in 33 patients. Neurologic findings likely related to ODDD were found in 11 patients. There appeared to be an association between the severity of syndactyly and the severity of dental and urologic findings, but not ophthalmologic or neurologic findings such as paraparesis or cognitive deficits. CONCLUSIONS: We found a 29% incidence of neurologic manifestations in patients with ODDD. In addition, associated ophthalmologic, dental, and developmental conditions are frequent and a heightened awareness will allow appropriate referrals for patients with ulnar-sided syndactyly in ODDD. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV. PMID- 22036283 TI - Functional splinting of upper limb injuries with gauze-based topical negative pressure wound therapy. AB - Complex hand injuries can be difficult to dress effectively and achieve adequate splintage of the hand in a functional position. During the past 7 years, we have had a great deal of success with topical negative-pressure dressings in the management of complex blast-related extremity war injuries. We have more recently changed to using a gauze-based system and have found this particularly useful in dressing complex hand injuries. We have been able to use this vacuum dressing system to splint the hand in a position of function. This provides an easily applied dressing that, through topical negative pressure, promotes wound healing and ensures a resting functional position, thus minimizing postoperative stiffness. We have not been able to achieve this as efficiently with standard dressings and plaster-of-Paris casts. This article details the technique of functional splinting of complex hand injuries using a gauze-based, topical negative-pressure dressing system. PMID- 22036284 TI - Hand injuries in rock climbing. PMID- 22036285 TI - The current state of hand transplantation. AB - Hand transplantation is the most common form of modern composite tissue allotransplantation. Successful application of this technology requires a multidisciplinary approach incorporating not only skilled hand surgeons, transplant surgeons, and transplant immunologists, but also hand therapists, psychiatrists, medical specialists, anesthesiologists, and others. Functional outcomes can be life changing for properly selected candidates. Hand transplantation is becoming more common, with more centers offering this relatively new reconstructive modality. Its success depends on proper patient selection, a technically successful operation, postoperative rehabilitation, and an immunotherapy protocol that prevents rejection but has minimal or acceptable morbidity. PMID- 22036286 TI - Ectopic banking of amputated parts: a clinical review. AB - Since its first clinical description by Marco Godina in 1986, the technique of temporary ectopic banking of amputated parts has been employed in a growing body of reported cases. This installment provides a review of the reported cases in the international literature to date, focusing on our evolving understanding of clinical indications, operative timing, and surgical technical consideration. Two illustrative cases are provided to highlight these concepts. PMID- 22036288 TI - Purification of a new fungal mannose-specific lectin from Penicillium chrysogenum and its aphicidal properties. AB - Several Ascomycetes fungi are commonly used in bio-industries and provide available industrial residues for lectin extraction to be valuable. A lectin from Penicillium chrysogenum, named PeCL, was purified from a fungal culture using gel filtration chromatography column. PeCL was found to be a mannose-specific lectin by haemagglutination activity towards rabbit erythrocyte cells and was visualised on SDS-PAGE gel. Purified PeCL fraction was delivered via artificial diet to Myzus persicae aphid and was demonstrated to be aphicidal at 0.1 % with higher toxic efficiency than a known mannose-binding lectin Concanavalin A (ConA). A fast and efficient way to purify PeCL and a potential use in pest control is described. PMID- 22036287 TI - Proceedings of the Second International Workshop on Advances in Electrocorticography. AB - The Second International Workshop on Advances in Electrocorticography (ECoG) was convened in San Diego, CA, USA, on November 11-12, 2010. Between this meeting and the inaugural 2009 event, a much clearer picture has been emerging of cortical ECoG physiology and its relationship to local field potentials and single-cell recordings. Innovations in material engineering are advancing the goal of a stable long-term recording interface. Continued evolution of ECoG-driven brain computer interface technology is determining innovation in neuroprosthetics. Improvements in instrumentation and statistical methodologies continue to elucidate ECoG correlates of normal human function as well as the ictal state. This proceedings document summarizes the current status of this rapidly evolving field. PMID- 22036289 TI - Phylogeny and intraspecific variation of the extreme xerophile, Xeromyces bisporus. AB - The filamentous ascomycete Xeromyces bisporus is an extreme xerophile able to grow down to a water activity of 0.62. We have inferred the phylogenetic position of Xeromyces in relation to other xerophilic and xerotolerant fungi in the order Eurotiales. Using nrDNA and betatubulin sequences, we show that it is more closely related to the xerophilic foodborne species of the genus Chrysosporium, than to the genus Monascus. The taxonomy of X. bisporus and Monascus is discussed. Based on physiological, morphological, and phylogenetic distinctiveness, we suggest that Xeromyces should be retained as a separate genus. PMID- 22036290 TI - Purification and partial characterisation of pectin methylesterase produced by Fusarium asiaticum. AB - Fusarium asiaticum is the predominant causal agent of Fusarium head blight (FHB) in China. When grown in liquid cultures containing potato tuber extract as the sole carbon source, F. asiaticum (strain 7071) from wheat (China) produced pectin methylesterase (PME), polygalacturonase (PG), and pectin lyase (PNL). The activity of these pectolytic enzymes was detected by a gel diffusion assay. Three forms of PME were identified in a culture filtrate of F. asiaticum. Two forms of PME with molecular weights of 31 kDa and 42.5 kDa, as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), were purified using a combination of chromatographic techniques. These PMEs did not bind to Concanavalin A (Con A), which was confirmed by rechromatography using a Con A agarose column. The 31 kDa purified PME was thermostable in a temperature range of 25-55 degrees C. The optimal pH for the PME of F. asiaticum was 6.5. This research provides the basis for future investigations of pectolytic enzymes from F. asiaticum. PMID- 22036291 TI - The highly variable mitochondrial small-subunit ribosomal RNA gene of Ophiostoma minus. AB - Mitochondrial genomes in the true fungi are highly variable both in size and organization. Most of this size variation is due to the presence of introns and intron-encoded open reading frames (ORFs). The objectives for this work were to examine the mitochondrial small-subunit ribosomal RNA (rns) gene of strains of Ophiostoma minus for the presence of introns and to characterize such introns and their encoded ORFs. DNA sequence analysis showed that among different strains of O. minus various rns gene exon/intron configurations can be observed. Based on comparative sequence analysis and RNA secondary structure modeling group I introns with LAGLIDADG ORFs were uncovered at positions mS569 and mS1224 and group II introns were present at positions mS379 and mS952. The mS379 group II intron encoded a fragmented reverse transcriptase (RT)-like ORF and the mS952 group II intron encoded a LAGLIDADG-type ORF. Examples of intron ORF degeneration due to frameshift mutations were observed. The mS379 group II intron is the first mitochondrial group II intron to have an ORF inserted within domain II, typically RT-like ORFs are inserted in domain IV. The evolutionary dynamics of the intron encoded ORFs have also been examined. PMID- 22036292 TI - Aspergillus niger contains the cryptic phylogenetic species A. awamori. AB - Aspergillus section Nigri is an important group of species for food and medical mycology, and biotechnology. The Aspergillus niger 'aggregate' represents its most complicated taxonomic subgroup containing eight morphologically indistinguishable taxa: A. niger, Aspergillus tubingensis, Aspergillus acidus, Aspergillus brasiliensis, Aspergillus costaricaensis, Aspergillus lacticoffeatus, Aspergillus piperis, and Aspergillus vadensis. Aspergillus awamori, first described by Nakazawa, has been compared taxonomically with other black aspergilli and recently it has been treated as a synonym of A. niger. Phylogenetic analyses of sequences generated from portions of three genes coding for the proteins beta-tubulin (benA), calmodulin (CaM), and the translation elongation factor-1 alpha (TEF-1alpha) of a population of A. niger strains isolated from grapes in Europe revealed the presence of a cryptic phylogenetic species within this population, A. awamori. Morphological, physiological, ecological and chemical data overlap occurred between A. niger and the cryptic A. awamori, however the splitting of these two species was also supported by AFLP analysis of the full genome. Isolates in both phylospecies can produce the mycotoxins ochratoxin A and fumonisin B2, and they also share the production of pyranonigrin A, tensidol B, funalenone, malformins, and naphtho-gamma-pyrones. In addition, sequence analysis of four putative A. awamori strains from Japan, used in the koji industrial fermentation, revealed that none of these strains belong to the A. awamori phylospecies. PMID- 22036293 TI - Molecular identification of two strains of Cercospora rodmanii isolated from water hyacinth present in Yuriria lagoon, Guanajuato, Mexico and identification of new hosts for several other strains. AB - Water hyacinth is a beautiful monocotyledon plant that has been dispersed all over the world by humans. The plant has been present in Mexico since 1907, and many water bodies have become infested with it since then. In 2001, we initiated a survey in Yuriria lagoon in southern Guanajuato state to isolate fungi able to biocontrol the plant. We isolated 25 morphologically distinct fungal cultures, of which two were identified as members of the genus Cercospora. Cercospora species are among the most prevalent and destructive of plant pathogens and can be found on leaves, pedicels, stems, fruits, and bracts. Only two species of Cercospora, Cercospora piaropi, and Cercospora rodmanii, have been described on water hyacinth; however, the classification of these species has been controversial. Several molecular approaches have been used for Cercospora identification, and some candidate genes have been identified for use in Cercospora species determination. Although the nrRNA genes alone do not show sufficient resolution for species determination, histone H3, translation elongation factor1-alpha, beta tubulin, actin, and calmodulin have been shown in previous studies to have an adequate number of nucleotide changes to allow species identification. In the present study, we used partial sequences of the histone H3, actin, and calmodulin genes to identify our two isolates as C. rodmanii. Our two strains are not specific to water hyacinth, as they are also pathogenic to beet and sugar beet. Similar host ranges were found for C. rodmanii strains isolated from Tabasco in Mexico, Zambia, and Brazil, however, the specificity for water hyacinth persists in Cercospora piaropi Tharp and C. rodmanii Conway, the latter being the most pathogenic. PMID- 22036294 TI - Modelling and visualizing morphology in the fungus Alternaria. AB - Alternaria is one of the most cosmopolitan fungal genera encountered and impacts humans and human activities in areas of material degradation, phytopathology, food toxicology, and respiratory disease. Contemporary methods of taxon identification rely on assessments of morphology related to sporulation, which are critical for accurate diagnostics. However, the morphology of Alternaria is quite complex, and precise characterization can be laborious, time-consuming, and often restricted to experts in this field. To make morphology characterization easier and more broadly accessible, a generalized statistical model was developed for the three-dimensional geometric structure of the sporulation apparatus. The model is inspired by the widely used grammar-based models for plants, Lindenmayer systems, which build structure by repeated application of rules for growth. Adjusting the parameters of the underlying probability distributions yields variations in the morphology, and thus the approach provides an excellent tool for exploring the morphology of Alternaria under different assumptions, as well as understanding how it is largely the consequence of local rules for growth. Further, different choices of parameters lead to different model groups, which can then be visually compared to published descriptions or microscopy images to validate parameters for species-specific models. The approach supports automated analysis, as the models can be fit to image data using statistical inference, and the explicit representation of the geometry allows the accurate computation of any morphological quantity. Furthermore, because the model can encode the statistical variation of geometric parameters for different species, it will allow automated species identification from microscopy images using statistical inference. In summary, the approach supports visualization of morphology, automated quantification of phenotype structure, and identification based on form. PMID- 22036295 TI - Differential expression of insect and plant specific adhesin genes, Mad1 and Mad2, in Metarhizium robertsii. AB - Metarhizium robertsii is an entomopathogenic fungus that is also plant rhizosphere competent. Two adhesin-encoding genes, Metarhizium adhesin-like protein 1 (Mad1) and Mad2, are involved in insect pathogenesis or plant root colonization, respectively. Here we examined the differential expression of the Mad genes when grown on a variety of soluble (carbohydrates and plant root exudate) and insoluble substrates (locust, tobacco hornworm, and cockroach cuticle, chitin, tomato stems, cellulose, and starch) and during insect, Plutella xylostella, infection. On insect cuticles Mad1 was up regulated, whereas bean root exudate and tomato stems resulted in the up regulation of Mad2. During the early stages of insect infection Mad1 was expressed while Mad2 was not expressed until fungal hyphae emerged and conidiated on the insect cadaver. The regulation of Mad2 was compared to that of other stress-related genes (heat shock protein (Hsp)30, Hsp70, and starvation stress gene A (ssgA)). Mad2 was generally up regulated by nutrient starvation (similar to ssgA) but not by pH, temperature, oxidative or osmotic stresses. Whereas Hsp30 and Hsp70 were generally up regulated at 37 degrees C or by oxidative stress even under nutrient enriched conditions. We fused the promoter of the Mad2 gene to a marker gene (green fluorescent protein (GFP)) and confirmed that Mad2 was up regulated when M. robertsii was grown in the presence of nutrient starvation. Examination of the promoter region of Mad2 revealed that it possessed two copies of a stress response element (STRE) known to be regulated under the general stress-response pathway. PMID- 22036296 TI - Diversity in the ability of Agaricus bisporus wild isolates to fruit at high temperature (25 degrees C). AB - The button mushroom Agaricus bisporus commercially cultivated requires 16-19 degrees C during the fruiting period. Wild strains are also present in natural habitat, and in light of their wide range of geographic distribution reported, from boreal region to tropical region, questions on the development adaptation to temperature arose. Isolates from various geographic areas were screened for their ability to fruit at higher temperature (FHT ability) than commercial cultivars. The FHT trait discriminated at the varietal rank. Agaricus bisporus var. eurotetrasporus was unable to develop any sporophores whilst A. bisporus var. burnettii adapted perfectly to 25 degrees C for fruiting, suggesting that the FHT ability is a fixed trait in these varieties. In contrast, FHT ability of A. bisporus var. bisporus appeared variable and correlated neither with climate/microclimate nor with habitat. However, FHT ability taken as a whole appeared higher in North American populations than in European ones. Some A. bisporus var. bisporus isolates revealed a good potential for cultivation at 25 degrees C. PMID- 22036297 TI - Health care professionals' understanding and day-to-day practice of patient empowerment in diabetes; time to pause for thought? AB - This exploratory study examines what Health Care Professionals (HCPs) working with diabetes patients, understand by the term 'empowerment', their attitudes towards it and whether they believe they practise in ways consistent with empowerment principles. A small sample of diabetes HCPs (N=13), from National Health Service (NHS) hospital, walk-in and General Practitioner (GP) clinics in South-East England, was interviewed. In-depth semi-structured interviews established attitudes towards and use of empowerment in day-to-day practice. Interviews were recorded, transcribed verbatim and analysed thematically. There was no clear specific understanding of what empowerment is and what it involves, although there was broad reporting of factors around education and informed choices. Disagreement was evident about the level of freedom patients should have in making choices - from leading them to the 'right' choice to an acceptance that they may have the right to choose not to be empowered. No consensus emerged on what is successful empowerment and how it is measured. The resistance of some patients to the process of empowerment in its original definition of active partnership in care, was seen as problematic by HCPs. Although empowerment is a popular concept in theory, its practical, clinical implementation day to day, can be problematic. PMID- 22036298 TI - Circus monkeys or change agents? Civil society advocacy for HIV/AIDS in adverse policy environments. AB - This paper explores the factors enabling and undermining civil society efforts to advocate for policy reforms relating to HIV/AIDS and illicit drugs in three countries in Eastern Europe and Central Asia: Georgia, Kyrgyzstan and Ukraine. It examines how political contexts and civil society actors' strengths and weaknesses inhibit or enable advocacy for policy change - issues that are not well understood in relation to specific policy areas such as HIV/AIDS, or particular regions of the world where national policies are believed to be major drivers of the HIV/AIDS epidemic. The study is based on in-depth interviews with representatives of civil society organizations (CSOs) (n = 49) and national level informants including government and development partners (n = 22). Our policy analysis identified a culture of fear derived from concerns for personal safety but also risk of losing donor largesse. Relations between CSOs and government were often acrimonious rather than synergistic, and while we found some evidence of CSO collective action, competition for external funding - in particular for HIV/AIDS grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria was often divisive. Development partners and government tend to construct CSOs as service providers rather than advocates. While some advocacy was tolerated by governments, CSO participation in the policy process was, ultimately, perceived to be tokenistic. This was because there are financial interests in maintaining prohibitionist legislation: efforts to change punitive laws directed at the behaviors of minority groups such as injecting drug users have had limited impact. PMID- 22036299 TI - [Optical coherence tomography applied to vessels: a bright future]. AB - Optical Coherence Tomography (OCT) is a new imaging technique recently applied to coronary and is based on the diffusion and reflection of an infrared spectrum. With a resolution 10 times higher than that of IVUS, it allows an analysis of the atherosclerotic plaque and its components, indicating its possible vulnerable character, and can identify the culprit lesion and the presence of thrombus in the course of acute events. It allows quality control of good apposition of stents to the wall and essentially tracks the downstream dissection. In the longer term, it evaluates the endothelisation and in-stent restenosis. Its scope thus extends to basic research and the pharmaceutical industry where it plays a new reference tool in the monitoring of atherosclerotic plaques and stents with drug treatment. This invasive imaging technique is limited by its cost and artifacts but new generation OCT can better overcome them. The OCT appears as a promising intravascular imaging technique whose feasibility and clinical applications, however, require confirmation by randomized clinical trials to better define its place in the cardiac catheterization lab. PMID- 22036300 TI - CaMKII antisense oligodeoxynucleotides protect against ischemia-induced neuronal death in the rat hippocampus. AB - The present study was performed to investigate the effects of Ca(2+)/calmodulin dependent protein kinase II (CaMKII) antisense oligodeoxynucleotides (ODNs) on the assembly of the CaMKII.GluR6.PSD-95 signaling module, GluR6 serine phosphorylation and c-Jun N-terminal kinase 3 (JNK3) activation. A further aim was to determine the neuroprotective mechanism of CaMKII antisense ODNs against ischemia-reperfusion (I/R)-induced neuronal death in the rat hippocampus. CaMKII antisense ODNs were intracerebroventricularly infused to inhibit CaMKII expression once daily for 3 days prior to the induction of ischemia. Transient cerebral ischemia (15 min) and reperfusion were induced by four-vessel occlusion in Sprague-Dawley rats as an animal model for transient cerebral I/R. The expression of related proteins was examined by immunoprecipitation and immunoblotting. Neuronal death in the rat hippocampus was detected by histology and histochemistry. The results indicate that CaMKII antisense ODNs inhibit several of the processes that are normally induced by cerebral I/R, including CaMKII expression, increased CaMKII.GluR6.PSD-95 signaling module assembly, GluR6 serine phosphorylation and JNK3 activation. Alternatively, CaMKII antisense ODNs also exhibit a significant neuroprotective role against cerebral I/R-induced cell death. These results provide the first evidence that CaMKII antisense ODNs can exert neuroprotective effects on cerebral I/R-induced cell death. The possible molecular mechanisms underlying this effect include 1) an inhibition of CaMKII expression and subsequent suppression of the assembly of the CaMKII.GluR6.PSD-95 signaling module, 2) GluR6 serine phosphorylation, and 3) reduced JNK3 activation. PMID- 22036301 TI - Improved model reduction and tuning of fractional-order PI(lambda)D(MU) controllers for analytical rule extraction with genetic programming. AB - Genetic algorithm (GA) has been used in this study for a new approach of suboptimal model reduction in the Nyquist plane and optimal time domain tuning of proportional-integral-derivative (PID) and fractional-order (FO) PI(lambda)D(MU) controllers. Simulation studies show that the new Nyquist-based model reduction technique outperforms the conventional H(2)-norm-based reduced parameter modeling technique. With the tuned controller parameters and reduced-order model parameter dataset, optimum tuning rules have been developed with a test-bench of higher order processes via genetic programming (GP). The GP performs a symbolic regression on the reduced process parameters to evolve a tuning rule which provides the best analytical expression to map the data. The tuning rules are developed for a minimum time domain integral performance index described by a weighted sum of error index and controller effort. From the reported Pareto optimal front of the GP-based optimal rule extraction technique, a trade-off can be made between the complexity of the tuning formulae and the control performance. The efficacy of the single-gene and multi-gene GP-based tuning rules has been compared with the original GA-based control performance for the PID and PI(lambda)D(MU) controllers, handling four different classes of representative higher-order processes. These rules are very useful for process control engineers, as they inherit the power of the GA-based tuning methodology, but can be easily calculated without the requirement for running the computationally intensive GA every time. Three-dimensional plots of the required variation in PID/fractional-order PID (FOPID) controller parameters with reduced process parameters have been shown as a guideline for the operator. Parametric robustness of the reported GP-based tuning rules has also been shown with credible simulation examples. PMID- 22036302 TI - How profitable is methamphetamine dealing in Australia? AB - INTRODUCTION: The illicit drug trade is the largest in value among global illicit commodities, at some $320 billion US dollars, according to the UN World Drug Report. Endeavours to control such a large illicit market would be enhanced by improved understanding of the economics of the trade. However, due to its illicit nature many aspects of the illicit drug market are largely unknown. This study explored one economic aspect of illicit drug dealing, profitability, with the aim of developing a better picture of the financial gains from illicit drug dealing. METHODS: Data were obtained from judges sentencing remarks, key informants from law enforcement, and other published reports which detail the prices paid for methamphetamine in Australia. The financial margins attained from non-crystal methamphetamine dealing in Australia were calculated by examining the best fit for the relationship between prices and quantities: in this case a power law. RESULTS: If it is assumed that a single deal is divided ("cut") between 4 times and 20 times before selling to the next customer, the mark-ups can range from 24% to 59%. The mark-ups appear low compared with those found in US research, but similar to those found in UK research. CONCLUSIONS: To our knowledge, this is the first attempt to analyse profitability of methamphetamine dealing in Australia. The findings of this study will help in understanding the motivations and decisions of drug dealers, and potentially assist drug law enforcement agencies to design better strategies to dismantle supply chain linkages which generate excessive profits. PMID- 22036303 TI - Illicit use of buprenorphine in a community sample of young adult non-medical users of pharmaceutical opioids. AB - BACKGROUND: There is growing evidence about illicit use of buprenorphine in the U.S. The study aims to: (1) identify prevalence and predictors of illicit buprenorphine use in a community sample of 396 young adult (18-23 years old) non medical users of pharmaceutical opioids and (2) describe knowledge, attitudes and behaviors linked to illicit buprenorphine use as reported by a qualitative sub sample (n=51). METHODS: Participants were recruited using respondent-driven sampling. Qualitative interview participants were selected from the larger sample. The sample (n=396) was 54% male and 50% white; 7.8% reported lifetime illicit use of buprenorphine. RESULTS: Logistic regression analysis results indicate that white ethnicity, intranasal inhalation of pharmaceutical opioids, symptoms of opioid dependence, and a greater number of pharmaceutical opioids used in lifetime were statistically significant predictors of illicit buprenorphine use. Qualitative interviews revealed that buprenorphine was more commonly used by more experienced users who were introduced to it by their "junkie friends." Those who used buprenorphine to self-medicate withdrawal referred to it as a "miracle pill." When used to get high, reported experiences ranged from "the best high ever" to "puking for days." Participants reported using buprenorphine/naloxone orally or by intranasal inhalation. Injection of buprenorphine without naloxone was also reported. CONCLUSION: Our findings suggest that illicit buprenorphine use is gaining ground primarily among whites and those who are more advanced in their drug use careers. Continued monitoring is needed to better understand evolving patterns and trends of illicit buprenorphine use. PMID- 22036304 TI - Functional recovery of untreated human immunodeficiency virus-associated Guillain Barre syndrome: a case report. AB - HIV-associated Guillain-Barre syndrome is a well-documented phenomenon, typically occurring at seroconversion. GBS may result in functional impairment treated with a combination of medications, plasmapheresis, and rehabilitation. The quantified functional recovery of HIV-associated GBS with or without HIV treatment is not well described. Utilizing serial FIM scoring, we describe a patient's recovery from HIV-associated GBS after treatment with IVIg and acute inpatient rehabilitation without HIV treatment. PMID- 22036305 TI - An electrochemical procedure to concentrate 99mTc availed from a zirconium [99Mo] molybdate gel generator. AB - Successful use of electrochemical method to concentrate (99m)Tc obtained from a zirconium molybdate (Zr(99)Mo) gel generator is reported. The process consists of electrodeposition of the (99m)Tc in an oxalate bath on a small platinum electrode followed by recovery of (99m)Tc in a small volume of normal saline. The overall recovery of (99m)Tc was >90% with >99.99% radionuclidic purity and >99% radiochemical purity. The compatibility of the product in the preparation of (99m)Tc labeled formulations such as (99m)Tc-DMSA and (99m)Tc-EC was found to be satisfactory in terms of high labeling yields (>98%). PMID- 22036306 TI - Maternal hair testing for the assessment of fetal exposure to drug of abuse during early pregnancy: Comparison with testing in placental and fetal remains. AB - Drug use by pregnant women in the first trimester of pregnancy and subsequent fetal exposure during early gestation can be assessed only by repetitive/systematic maternal blood/urine analysis or segmental hair analysis. No evidence of any relationship between maternal/fetal exposure during this specific period of gestation has been demonstrated to date in a human model. METHODS: To clarify drugs toxicokinetics and transplacental passage during early pregnancy, the presence of the most widely used recreational drugs of abuse and metabolites was investigated in the proximal 4cm hair segments of women undergoing voluntary termination of pregnancy (n=280) during the 12th week of gestation and the results were compared to those from placenta and fetal tissue samples in order to verify whether maternal hair testing can reflect fetal exposure and, if so, to what extent. Hair, placenta and fetal remains were analyzed by validated gas chromatography mass spectrometry assays. RESULTS: Eighty one positive hair samples were identified: 60 were positive for cannabis (74.1%), 28 for cocaine (34.6%), 7 for opiates (8.6%), 3 for MDMA (3.7%) and 18.5% were positive for more than one drug. The positive hair test results were confirmed in placenta/fetal tissues in 10 cases out of 60 for cannabis (16. 7%); in 7 out of 28 for cocaine (25%); and none for the 6 opiates positive cases and 3 MDMA cases, respectively. CONCLUSION: Drugs/metabolites in hair of pregnant women can be used as biomarkers of past drug use (repetitive or sporadic), although the use is not always reflected in fetal/placental tissues. There are several possible hypotheses to explain the results: (1) the use occurred before the start of pregnancy, (2) past sporadic consumption which could be measured in hair but not in fetal and placental remains because of the narrow window of drug detection in placental/fetal tissues; (3) the sensitivity of the analytical methods was not high enough for the detection of the minute amount of drugs of abuse and metabolites which reached these tissues (4) there is a large variability in the transplacental passage of drugs of abuse and in the placenta's metabolizing capacity. PMID- 22036307 TI - Automated fast procedure for the simultaneous extraction of hair sample performed with an automated workstation. AB - INTRODUCTION: Hair testing has a leading role in toxicology practice and even more in those aspects tightly linked to the assessment of psychoactive drug use and abuse in social life. AIM: The objective of the present study was to develop and validate an automated SPE sample-preparation step, suited for GC/MS confirmation analysis of basic drugs in hair drug control. The method was studied and optimized for quantitative determination and in a second time it was extended to real hair samples. The purpose of method validation was to ensure good reliability, reproducibility and quickness. METHODS: Janus Automated Workstation (PerkinElmer) was employed to perform SPE hair extraction, using 96-well plate SPEC MP1 acquired from Varian (Agilent Technologies). After derivatization of dried extracts, screening confirmations were performed using gas chromatography (GC) followed by mass spectrometry (MS). GC/MS data were validated following standard guidelines, but our attention was focused on three headings: samples cross-contamination, "memory effect" and extraction recovery. RESULTS: Validation requests were fully accomplished and we always obtained best results with the automated procedure. For instance, analytes mean recovery was between 70 and 90% and data analysis proved that no contamination between samples occurred. CONCLUSIONS: The automated workstation has shown good reliability (cross contamination and "memory effect" were tested and excluded), effectiveness (no false negative was detected), solvent saving (500MUL/sample vs traditionally LLE 4mL/sample) and quickness (50min for 96 tests cycle). PMID- 22036308 TI - Detection and quantification of 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid in hair by GC/MS/MS in Negative Chemical Ionization mode (NCI) with a simple and rapid liquid/liquid extraction. AB - INTRODUCTION: The fine detection of 11-nor-Delta9-tetrahydrocannabinol-9 carboxylic acid (THCCOOH) in hair matrix remains one of the most important topics in hair analysis. This relevance lies in the necessity to obtain evidence of effective drug consumption and dispel any doubt of environmental contamination. THCCOOH is the highest and mainly represented Delta9-THC metabolite, but its concentration in hair is very low. A sensitive method for quantitative determination of THCCOOH in hair was developed. As first step, the method was tested with different SPE/LLE conditions, but the best results were obtained with a simple ad hoc LLE extraction. The final method was fully validated, evaluating parameters like extraction recovery, linearity, specificity and sensitivity. More than one hundred hair samples were then analyzed with the validated method. Data analysis was performed so as to determine respective concentrations of the metabolite and active molecule. METHODS: Hair was washed and cut into small pieces (2-4mm). Samples (20-50mg) were spiked with deuterated internal standard (THC-d(3) and THCCOOH-d(3)) and then hydrolyzed at 90 degrees C in 1mL of 1M NaOH for 15min. THC was isolated by a LLE basic extraction with n-hexane:ethyl acetate (9:1). Next the aqueous solution was acidified (pH 4) adding concentrated acetic acid. THCCOOH was extracted with the same mixture. Dried extracts were derivatized with pentafluoropropionic anhydride and hexafluoroisopropanol and analyzed by GC/MS/MS (Agilent 7000B triple quadrupole) in NCI mode. RESULTS: The linear range of THCCOOH is 0.1-5pg/mg, with good correlation coefficients (r(2)>0.9993). This method has great sensitivity (LOD 0.01pg/mg to LOQ 0.04pg/mg), high recovery, reproducibility and robustness. CONCLUSIONS: Based on these results, the method proved to be effective for the rapid determination of THC and THCCOOH in hair specimens. PMID- 22036309 TI - Practical experiences in application of hair fatty acid ethyl esters and ethyl glucuronide for detection of chronic alcohol abuse in forensic cases. AB - This article presents results from 1872 hair samples, which were analyzed for fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG). The results were evaluated in the context of self-reported drinking behavior, the use of hair cosmetics, the gender of the sample donors and hair sample length. For comparison, CDT and GGT in serum were available in 477 and 454 cases, respectively. A number of alcohol abstainers or low moderate drinkers and excessive drinkers were selected for assessment of cut-offs for FAEEs in the proximal 6cm hair segments and for EtG in the proximal 3cm hair segments. Cut-off values were assessed by ROC analysis. It was found that the cut-offs of 1.0ng/mg FAEE and 30pg/mg EtG presently used for excessive drinking lead to a low portion of false positives (4% and 3% respectively) but to a higher portion of false negatives (23% and 25% respectively). Comparison of the mean and medium concentrations in samples without any reported hair cosmetics (N=1079) and in samples with reported use of hair spray (N=79) showed an increase by the factor of about two for FAEE but no significant difference for EtG. Mean values of EtG were decreased by 80% in bleached samples (N=164) and by 63% in dyed samples (N=96). There was no significant effect of bleaching and dyeing on FAEE. Hair gel and hair wax, oil or grease showed no significant effect on both FAEE and EtG. With respect to gender and investigated hair length ambiguous results were obtained because of major differences in the compared subpopulations of male with higher alcohol consumption and mainly shorter hair, and less drinking female with longer hair. For excessive drinkers FAEEs in the 0-6cm hair segment and EtG in the 0-3cm segment decreased with increasing time of reported abstinence before sample collection. These drinkers attain the level of teetotalers only after more than 10 months of abstinence. In comparison to scalp hair, FAEEs recovered from armpit hair and leg hair were lower and from chest hair were higher. EtG in armpit hair was lower and in leg hair higher than in scalp hair. It is concluded that the combined use of FAEE and EtG essentially increases the accuracy of interpretation since both markers complement each other by a different sensitivity to sources of error. PMID- 22036310 TI - General unknown screening in hair by liquid chromatography-hybrid quadrupole time of-flight mass spectrometry (LC-QTOF-MS). AB - The retrospective investigation of the exposure to toxic substances by general unknown screening of hair is still a difficult task because of the large number of possible poisons, the low sample amount and the difficult sample matrix. In this study the use of liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was tested as a promising technique for this purpose. In the optimized procedure, 20mg hair were decontaminated with water and acetone and two times extracted by 18h incubation with 0.5ml of a mixture of methanol/acetonitrile/H(2)O/ammonium formate at 37 degrees C. A mixture of deuterated standards from different drug groups was added for quantification and method control. The united extracts were evaporated to a residue of 0.5ml and 5MUl were injected without clean-up for LC-QTOF-MS measurement (instrument Agilent 6530) with positive electrospray ionization and in data dependent acquisition mode. For peak identification the accurate mass data base and spectral library of the authors was used which contains accurate mass CID spectra of more than 2500 and theoretically calculated accurate mass data of more than 7500 toxicologically relevant substances. Validation at the example of 24 illegal drugs, their metabolites and benzodiazepines resulted in limits of detection of 0.003-0.015ng/mg, and limits of quantification of 0.006-0.021ng/mg with good accuracy and intra- and interday reproducibility. The matrix effect by ion suppression/enhancement was 72-107% for basic drugs and 42-75% for benzodiazepines. Yields of the hair extraction above 90% were determined for 59 drugs or metabolites. The method was applied to hair samples from 30 drug fatalities and from 60 death cases with known therapeutic drug intake at life time. Altogether 212 substances were identified with a frequency per drug of 1-40 (mean 4.2) and per case of 2-33 (mean 10.2), between them 35 illegal drug related substances and 154 therapeutic drugs. Comparison with the data known from case histories and from the analysis of blood, urine and gastric content showed only a low agreement, with many unexpected drugs detected and many reported drugs not detected in hair. Basic drugs and metabolites such as opioides, cocaine, amphetamines, several groups of antidepressants, neuroleptics, beta-blockers or the metamizole metabolite noramidopyrine were found with high frequency whereas acidic and several neutral drugs such as cannabinoids, salicylic acid, furosemide, barbiturates, phenprocoumone or cardiac glycosides could not be detected with sufficient sensitivity, mainly because of the low ion yield of positive ESI for these compounds. The advantage of a comprehensive acquisition of all substances is paid by a lower sensitivity in comparison to targeted screening LC-MS/MS procedures. In conclusion, the procedure of sample preparation and LC QTOF-MS analysis proved to be a robust and sensitive routine method in which the qualitative screening for a wide variety of toxic substances in hair is combined with the quantitative determination of selected illegal drugs. PMID- 22036311 TI - Behavioural problems in school age children with cerebral palsy. AB - BACKGROUND: Although behavioural problems are frequent in children with Cerebral Palsy (CP), the exact nature of these difficulties and their relationship with intrinsic or extrinsic factors are just beginning to be explored. AIM: To describe and characterize behavioural problems in children with CP and to determine the nature of any relationships with child and family characteristics. METHODS: In this cross-sectional study, children with CP between 6 and 12 years of age were recruited. Children were assessed using the Leiter Intelligence Test, the Gross Motor Function Measure, the Strengths and Difficulties Questionnaire (SDQ), the Vineland Adaptive Behavior Scales and questionnaires on demographic factors. Parents' level of stress was measured with the Parenting Stress Index. RESULTS: Seventy-six parents completed the SDQ. Using the Total Difficulties Scores, 39.4% of the sample scored in the borderline to clinically abnormal range. Peer problems were the most common (55.3%). High parental stress was consistently associated with behavioural difficulties across all domains of the SDQ. Not surprisingly, better socialization skills and a lower parental stress were correlated with more positive behaviours. CONCLUSION: Behavioural difficulties are common in children with CP and appear not to be associated with socio-demographic variables and physical and cognitive characteristics. These difficulties are an important correlate of parental distress. This study emphasizes the need to recognize and address behavioural difficulties that may arise so as to optimize the health and well-being of children with CP and their families. PMID- 22036312 TI - Inefficient splicing of segment 7 and 8 mRNAs is an inherent property of influenza virus A/Brevig Mission/1918/1 (H1N1) that causes elevated expression of NS1 protein. AB - Influenza A virus encodes two segments (7 and 8) that produce mRNAs that can be spliced. We have investigated if naturally occurring sequence polymorphisms in the influenza A virus family affects splicing of these viral mRNAs, as that could potentially alter the NS1/NS2- and/or M1/M2-protein ratios. We compared splicing efficiency of segment 7 and 8 mRNAs of A/Brevig Mission/1918/1 (H1N1) and A/Netherlands/178/95 (H3N2), as well as various H5N1 avian strains. Results revealed that both segment 7 and 8 mRNAs of A/Brevig Mission/1918/1 (H1N1) were inefficiently spliced compared to other influenza virus segment 7 and 8 mRNAs. This resulted in production of higher levels of functional NS1 protein, which could potentially contribute to the pathogenic properties of the A/Brevig Mission/1918/1 (H1N1). We also show that A/Brevig Mission/1918/1 (H1N1) segment 8 mRNAs responded differently to overexpression of SR proteins than A/Netherlands/178/95 (H3N2). PMID- 22036313 TI - Role of arginine-56 within the structural protein VP3 of foot-and-mouth disease virus (FMDV) O1 Campos in virus virulence. AB - FMDV O1 subtype undergoes antigenic variation under diverse growth conditions. Of particular interest is the amino acid variation observed at position 56 within the structural protein VP3. Selective pressures influence whether histidine (H) or arginine (R) is present at this position, ultimately influencing in vitro plaque morphology and in vivo pathogenesis in cattle. Using reverse genetics techniques, we have constructed FMDV type O1 Campos variants differing only at VP3 position 56, possessing either an H or R (O1Ca-VP3-56H and O1Ca-VP3-56R, respectively), and characterized their in vitro phenotype and virulence in the natural host. Both viruses showed similar growth kinetics in vitro. Conversely, they had distinct temperature-sensitivity (ts) and displayed significantly different pathogenic profiles in cattle and swine. O1Ca-VP3-56H was thermo stable and induced typical clinical signs of FMD, whereas O1Ca-VP3-56R presented a ts phenotype and was nonpathogenic unless VP3 position 56 reverted in vivo to either H or cysteine (C). PMID- 22036314 TI - Parameters of donor-recipient size mismatch and survival after bilateral lung transplantation. AB - BACKGROUND: The purpose of this study was to investigate the relationship between donor-recipient height, gender and predicted estimates of total lung capacity (pTLC) mismatches and post-transplant survival. METHODS: The lung transplant databases at three programs were reviewed. The pTLC ratios (donor pTLC/recipient pTLC) and height ratios (donor height/recipient height) were calculated retrospectively. Patients were grouped according to pTLC ratio <=1.0 or >1.0 and height ratio <=1.0 or >1.0, and according to gender (mis-)matching. A time-to event analysis was performed for risk of death after transplantation conditional on 30-day survival using Kaplan-Meier survival and Cox proportional hazard models. RESULTS: There were 211 adult bilateral lung transplant recipients who qualified for the analysis. Mean follow-up was comparable for all cohorts (range 2.21 to 3.85 years). In the univariate Cox proportional hazard models, a pTLC ratio >1.0 (HR 0.43, p = 0.002) and a height ratio >1.0 (HR 0.61, p = 0.03) were associated with better survival, and a female-donor-to-male-recipient gender mismatch (F-to-M) was associated with worse survival (HR 2.35, p = 0.01). In the multivariate Cox proportional hazard model accounting for F-to-M gender mismatch and height ratio >1.0, a pTLC ratio >1.0 remained associated with survival (HR 0.38, p = 0.015). However, accounting for a pTLC ratio >1.0, a height ratio of >1.0 and F-to-M mismatch were not associated with survival. CONCLUSIONS: A pTLC ratio >1.0 is associated with improved survival after bilateral lung transplantation. The pTLC ratio might better reflect allograft-thorax mismatch than the height ratio, as it also accounts for effects of gender on lung and thoracic volumes. PMID- 22036315 TI - Theoretical investigations of alpha,alpha,alpha-trifluoro-3, -p and o nitrotoluene by means of density functional theory. AB - This study reports the optimized molecular structures, vibrational frequencies including Infrared intensities and Raman activities, corresponding vibrational assignments, (1)H and (13)C NMR chemical shifts, the magnitudes of the JCH and JCC coupling constants, Ultraviolet-visible (UV-vis) spectra, thermodynamic properties and atomic charges of the title compounds, alpha,alpha,alpha-trifluoro 3, -p and o-nitrotoluene, in the ground state by means of the density functional theory (DFT) with the standard B3LYP/6-311++G(d,p) method and basis set combination for the first time. Theoretical vibrational spectra were interpreted by normal coordinate analysis based on scaled density functional force field. The results show that the vibrational frequencies and chemical shifts calculated were obtained to be in good agreement with the experimental data. Based on the comparison between experimental results and theoretical data, the calculation level chosen is powerful approach for understanding the identification of all the molecules studied. In addition, not only were frontier molecular orbitals (HOMO and LUMO), molecular electrostatic potential (MEP) and electrostatic potential (ESP) simulated but also the dipole moment, softness, electronegativity, chemical hardness, electrophilicity index, transition state and energy band gap values were predicted. According to the investigations, all compounds were found to be useful to bond metallically and interact intermolecularly; however, the thermodynamic properties confirm that the alpha,alpha,alpha-trifluoro-p nitrotoluene was more reactive and more polar than the others. PMID- 22036316 TI - Metal-enhanced fluorescence exciplex emission. AB - In this letter, we report the first observation of metal-enhanced exciplex fluorescence, observed from anthracene in the presence of diethylaniline. Anthracene in the presence of diethylaniline in close proximity to Silver Island Films (SIFs) shows enhanced monomer and exciplex emission as compared to a non silvered control sample containing no silver nanoparticles. Our findings suggest two complementary methods for the enhancement: (i) surface plasmons can radiate coupled monomer and exciplex fluorescence efficiently, and (ii) enhanced absorption (enhanced electric near-field) further facilitates enhanced emission. Our exciplex studies help us to further understand the complex photophysics of the metal-enhanced fluorescence technology. PMID- 22036317 TI - Cognitive function in morbidly obese individuals with and without binge eating disorder. AB - OBJECTIVE: Obesity is associated with poorer cognitive function and impulsivity, which may contribute to binge eating disorder (BED). The objective of this study was to compare cognitive function in morbidly obese individuals with and without BED. METHOD: A total of 131 morbidly obese individuals (41 with past or present BED, 90 with no BED history) completed a computerized battery of cognitive tests including executive, memory, language, and attention. RESULTS: Both groups of participants evidenced high rates of cognitive impairment; however, no significant differences emerged between persons with and without BED on cognitive testing. Comparison of persons without BED, current BED, and past BED also yielded no differences. DISCUSSION: In the present sample, morbidly obese individuals with and without BED were clinically indistinguishable on tests of cognitive function. Our findings suggest that obesity, rather than binge eating, may be more directly related to cognition. Future studies should further examine this relationship because it might provide greater insight into the neural mechanisms for this BED. PMID- 22036318 TI - Starvation and emotion regulation in anorexia nervosa. AB - Self-starvation, with concomitant weight loss, may serve as a dysfunctional behavior to attenuate negative affective states in anorexia nervosa (AN). A total of 91 participants composed of patients with acute AN, women recovered from AN, clinical controls with either depression or anxiety disorder, and healthy controls were tested on a measure of emotion regulation. Patients with acute AN as well as recovered patients with AN and clinical controls showed increased emotion regulation difficulties as compared with healthy controls. In patients with acute AN, a specific association between body weight and emotion regulation was found: the lower the body mass index in patients with acute AN, the lesser were their difficulties in emotion regulation. This association could only be found in the subsample of patients with acute AN but not in the control groups. Moreover, there were no confounding effects of depression or duration of illness. The findings are consistent with the hypothesis that self-starvation with accompanying low body weight serves as a dysfunctional behavior to regulate aversive emotions in AN. PMID- 22036320 TI - Assessing health in children: national surveys and the role of the laboratory. PMID- 22036322 TI - Metabolomics in neonatology and pediatrics. PMID- 22036323 TI - Unified prenatal screening for Down's syndrome and pre-eclampsia. PMID- 22036324 TI - Fetal scalp blood measurements during labour-lactate or pH? PMID- 22036325 TI - Contemporary issues in fetal lung maturity testing. PMID- 22036326 TI - Fetal health assessment in utero by laboratory technologies: clinical benefits, risks and controversies. PMID- 22036327 TI - Neonatal sepsis: a difficult diagnostic challenge. PMID- 22036328 TI - Investigations for neonatal hypoglycaemia. PMID- 22036329 TI - Future directions in metabolic disease testing. PMID- 22036330 TI - Newborn screening from an international perspective--different countries, different approaches. PMID- 22036331 TI - Role of mutation analysis for the diagnosis of inborn errors of metabolism. PMID- 22036332 TI - Selective screening for inborn errors of metabolism--assessment of metabolites in body fluids. PMID- 22036333 TI - Dried blood spots in the diagnosis of lysosomal storage disorders--possibilities for newborn screening and high-risk population screening. PMID- 22036334 TI - Reference intervals: the GB data. PMID- 22036335 TI - KiGGS-the German survey on children's health as data base for reference intervals. PMID- 22036336 TI - Closing the gaps in pediatric reference intervals: the CALIPER initiative. PMID- 22036337 TI - Critical values for the maternal-fetal unit, fetus, infant, child and adolescent: bilirubin reporting practice in North American Children's Hospitals as a paradigm for critical value reporting assessment. PMID- 22036338 TI - Prenatal and newborn screening for CFTR mutations: the difficulties of prediction. PMID- 22036339 TI - A continuing role for sweat testing in an era of newborn screening for cystic fibrosis. PMID- 22036340 TI - Nutrition-related derangements and managements in patients with cystic fibrosis: robust challenges for preventing the development of co-morbidities. PMID- 22036341 TI - If I'd known I was going to live this long, I'd have taken better care of myself: antioxidants and micronutrients in CF. PMID- 22036342 TI - Primary immunodeficiencies--the role of the laboratory. PMID- 22036343 TI - Development and regulation of immune responses in pre- and postnatal life. PMID- 22036344 TI - Multiplex PCR for detection of respiratory viruses: can the laboratory performing a respiratory viral panel (RVP) assay trigger better patient care and clinical outcomes? PMID- 22036345 TI - Diagnosis of congenital renal anomalies in children. PMID- 22036346 TI - NGAL--from discovery to a new era of "acute renal disease" diagnosis? PMID- 22036347 TI - Cystatin C- and creatinine-based GFR-prediction equations for children and adults. PMID- 22036348 TI - Renal tubular disorders: from proteins to patients. PMID- 22036349 TI - Congenital adrenal hyperplasia. PMID- 22036350 TI - Dyslipidemias in children and adolescents. PMID- 22036351 TI - Diagnostic pathways in disorders of sex development. PMID- 22036352 TI - Molecular diagnosis of genetic deafness. PMID- 22036353 TI - Inherited coagulation disorders in children with arterial ischemic stroke and transient ischemic attack. PMID- 22036354 TI - Next generation sequencing: the technology we need in pediatric laboratories? PMID- 22036355 TI - Point-of-care testing: is it a must in pediatrics? PMID- 22036356 TI - Metabolomic studies at the start and end of the life cycle. PMID- 22036449 TI - Subjective stress factors in centrifuge training for military aircrews. AB - This study investigates stress-influence factors perceived by military aircrews undergoing centrifuge training, which lowers the incidence of G-induced loss of consciousness (G-LOC) for the crews of high-performance combat aircrafts. We used questionnaires to assess the subjective stress-influence factors of crews undergoing centrifuge training. Professionals in aviation physiology identified attributes measuring the perceived stress induced by centrifuge training, which were segmented into three constructs by factor analysis, theory lecture, centrifuge equipment, and physical fitness. Considerable interpenetration was discernible between these factors and military rank, age, length of service, flight hours accrued, and type of aircraft piloted. Identifying and quantifying the perceived stressors experienced in human-use centrifuge training enables aviators, astronauts, and air forces of the world to determine which constructs perceptibly increase or alleviate the perceived stress undergone by trainees when partaking in centrifuge training. PMID- 22036450 TI - Musculoskeletal disorder risk during automotive assembly: current vs. seated. AB - Musculoskeletal disorder risk was assessed during automotive assembly processes. The risk associated with current assembly processes was compared to using a cantilever chair intervention. Spine loads and normalized shoulder muscle activity were evaluated during assembly in eight regions of the vehicle. Eight interior cabin regions of the vehicle were classified by reach distance, height from vehicle floor and front to back. The cantilever chair intervention tool was most effective in the far reach regions regardless of the height. In the front far reach regions both spine loads and normalized shoulder muscle activity levels were reduced. In the middle and close reach regions spine loads were reduced, however, shoulder muscle activity was not, thus an additional intervention would be necessary to reduce shoulder risk. In the back far reach region, spine loads were not significantly different between the current and cantilever chair conditions. Thus, the effectiveness of the cantilever chair was dependent on the region of the vehicle. PMID- 22036451 TI - Tightrope fixation of ankle syndesmosis injuries: clinical outcome, complications and technique modification. AB - BACKGROUND: Ankle syndesmotic injuries are complex and require anatomic reduction and fixation. Tightrope fixation is a relatively new technique and we present the largest series of syndesmosis fixation using Arthrex TightropeTM (Naples, FL, USA). MATERIALS AND METHODS: Forty-nine patients with ankle diastasis, treated with Arthrex tightropeTM, were reviewed retrospectively, using American Orthopaedic Foot and Ankle Society (AOFAS) and Foot and Ankle Disability Index (FADI) scores and radiographic parameters for syndesmosis integrity. The operative technique was slightly modified by the senior author in 31 cases to avoid soft-tissue complications requiring removal of the implant. The aim of this study was to assess the rate of hardware removal after tightrope fixation and the effect of the author's modification to avoid soft-tissue complications. RESULTS: The mean age of patients was 37.7 years. Eighteen were performed with standard technique whilst 31 with the modified technique. The mean radiological follow-up was 6 months. Final data were collected using a confidential questionnaire and FADI score at an average of 24 (12-38) months postoperatively. The average time to full weight bearing was 7.7 weeks and to return to normal activities was 11.2 weeks. Postoperative radiographic measurements demonstrated satisfactory reduction of syndesmosis. The Mean AOFAS score was 85.57 (95% confidence interval (CI) 77.96-93.18) and the mean FADI score was 81.20 (95% CI 73.86-88.53). There were three cases of hardware removal in the standard technique group as compared to none in the group with the modified technique. CONCLUSION: Arthrex TightropeTM provides an effective method of syndesmosis stabilisation, which obviates the need for routine removal of implant and facilitates dynamic stabilisation. The results of this study are satisfactory and comparable to previously reported studies. We emphasise that surgeons must be aware of the potential risk of soft tissue complications and recommend our modified technique. Further long-term prospective studies should be carried out to resolve this issue. PMID- 22036452 TI - Radiographic follow-up of 84 operatively treated scapula neck and body fractures. AB - BACKGROUND: Certain scapula fractures may warrant surgical management to restore shoulder anatomy and promote optimal function. The purpose of this study is to determine the early radiographic follow-up of open reduction internal fixation (ORIF) for displaced, scapular fractures involving the glenoid neck and body. METHODS: Eighty-four patients with a scapula body or neck fracture (with or without articular involvement) underwent ORIF between 2002 and 2010 at a single level I trauma centre. This study represents a retrospective review of data prospectively collected into a dedicated scapula fracture database. All patients met at least one of the following operative criteria: >=20 mm medial/lateral (M/L) displacement (lateral border offset), >=45 degrees of angular deformity on a scapular-Y X-ray, the combination of angulation >=30 degrees plus M/L displacement >=15 mm, double disruptions of the superior shoulder suspensory complex both displaced >=10 mm, glenopolar angle (GPA) <=22 degrees and open fractures. Eighty-eight percent (74/84) had sufficient follow-up defined as at least 6 months. Measured outcomes included rates of scapula union and malunion, as well as surgical complications and re-operations. RESULTS: All fractures were caused by high-energy trauma with 24 (29%) resulting from motor-vehicle collisions. Associated injuries occurred in 94% of patients, most commonly involving the chest (70%) and ipsilateral shoulder girdle (43%). Forty-eight patients had M/L displacement as an operative indication with a mean displacement of 25.7 mm (range=20-40). Thirty-eight (45%) had >=2 operative indications. A single surgeon performed ORIF in all patients using a posterior approach. Five patients also required an anterior (deltopectoral) approach. The fixation strategy included lateral and vertebral border stabilisation with dynamic compression and reconstruction plates, respectively. Union was achieved in all cases. There were three cases of malunion based on a GPA difference >10 degrees from the uninjured shoulder. Re-operations included removal of hardware (seven patients) and manipulation under anaesthesia (three patients). There were no infections or wound dehiscence. CONCLUSIONS: ORIF for displaced scapula fractures is a relatively safe and effective procedure for restoration of anatomy and promotion of union. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 22036453 TI - Estimating foot inertial parameters: a new regression approach. AB - BACKGROUND: Estimating the inertial parameters for the foot (mass, center of mass position and inertia tensor) is important for applications involving the ankle joint such as inverse dynamics or stiffness measurement techniques (e.g. Quick release). Scaling equations relying on foot length and body mass are widely used. However, because of the complex foot geometry, such equations may represent an oversimplified solution. Our aim was to evaluate these approaches and propose a new method. METHODS: Thirty-four right feet (17 Males, mean age and weight 30 years, 75 kg; 17 Females, 32 years, 61.5 kg) were reconstructed using a 3D surface scanner and used as geometrical references. Associated inertial parameters were calculated directly on each reference assuming a uniform density distribution and were compared to corresponding scaling and multiple regression estimates. Finally, an alternative method, based on multiple non-linear regressions, was proposed considering both foot length (L) and ankle width (W). FINDINGS: Comparisons showed that reference mass and moments of inertia were greater than scaling predictions with mean difference up to 33 and 16% for mass and moments of inertia respectively. The maximum standard errors of estimate for scaled moments of inertia reached 26%. The alternative solution involving ankle width in the equations lowered the gap with reference data (8.7% max standard errors of estimate) for both genders. INTERPRETATION: This strategy, requiring two simple and accessible measurements, may offer a better practicality/relevance compromise for clinical routine use, in regards to existing scaling and regression equations. PMID- 22036454 TI - [Paget-Schroetter syndrome]. PMID- 22036455 TI - [Relationship between myocardial modelling and diastolic function in patients with essential hypertension]. AB - BACKGROUND AND OBJECTIVES: To analyze the relationship between sFas and soluble TNF receptor 1 (sTNF-R1) with type iii (PIIINP) and i (PINP) amino-terminal propeptide procollagens, and diastole in hypertension (HT). PATIENTS AND METHODS: A group of 253 Caucasian asymptomatic hypertensive patients (age 60+/-13 years, 139 males) were studied, in whom a physical examination, laboratory analyses (determination of serum PIIINP, PINP, sFas and by radioimmunoassay and ELISA, respectively), and echo-Doppler study were performed. RESULTS: Serum PINP and PIIINP were increased in left ventricular hypertrophy compared to non-hypertrophy [41 (31-52) vs. 35 (28-47) MUg/l, P=.010; and 4.33 (3.71-5.29) vs. 3.98 (3.49 4.58) MUg/l, P=.005, respectively]. Furthermore, sFas and sTNF-R1 were also elevated [1.47 (1.2-1.77) vs. 1.37 (1.1-1.59), P=.012; and 466 (331-657) vs. 317 (260-427) MUg/l, P<.0001, respectively]. Moreover, serum PIIINP was associated with sFas (r=.386, P<.0001) and sTNF-R1 (r=.298, P<.001); PINP was also associated with these cytokines (r=0.158, P=.011 and r=.241, P<.0001, respectively). Multivariable analyses included sFas (P<.0001) and sTNF-R1 (P<.0001) as independent factors related with serum PIIINP. Finally, marker concentrations were significantly related with left ventricular diastolic function parameters. CONCLUSION: Procollagen and anti-apoptotic cytokine levels were increased in our hypertrophic patients. Furthermore, sFas and sTNF-R1 are independent related factors of serum PIIINP. Diastolic parameters were associated with myocardial fibrosis and anti-apoptotic cytokines. PMID- 22036456 TI - [Numerical understanding deficit. Mathematics as a problem]. PMID- 22036460 TI - [Role of ecocardiogram in fever of unknown origin. Towards saturation of echocardiogram laboratories? Reply]. PMID- 22036458 TI - [Inertia and treatment compliance in patients with type 2 diabetes in primary care]. AB - BACKGROUND AND OBJECTIVES: Therapeutic inertia (TI) and therapeutic compliance (TC) are 2 important barriers in achieving the therapeutic objectives recommended for patients with diabetes mellitus type 2 (DM2). This study analyzes the TI in patients with DM2 who do not achieve the glycemic, blood pressure (BP) and LDL cholesterol (c-LDL) control goals, the patients' TC and the relationship between TI and TC. PATIENTS AND METHODS: This is a descriptive study conducted in a Primary Health Care center. We included 320 diabetic patients. Objectives of control were HbA1c <= 7%, blood pressure (BP) <= 130/80 mm Hg, c-LDL <= 100 mg/dl, TI (when the objectives of control were not reached and the professional did not change the treatment) and TC (by counting withdrawals of pharmacy prescriptions). RESULTS: The objectives of control for HbA1c, BP and c-LDL were reached by 66.4, 43.2 and 40.5% of patients, respectively. There was TI in the 86.4% of patients for c-LDL, in 76.7% for BP and in 40.6% for HbA1c. The percentage of therapeutic non-compliance was of 36.1, 37.5 and 32.0% for antidiabetic, antihypertensive and lipid lowering drugs, respectively. Elderly patients were better compliants. TI and TC were not associated. We did not find differences in the level of control, TI, use of drugs and TC by sex. CONCLUSIONS: TI and TC play an important role in the non-consecution of the control objectives in diabetic patients, especially regarding BP and lipids. TC is not related to TI. PMID- 22036461 TI - [Adie's pupil]. PMID- 22036462 TI - [Pseudopapillary solid tumor of the pancreas: report of 6 cases]. AB - BACKGROUND AND OBJECTIVES: Solid pseudopapillary neoplasms (SPNs) are rare tumours of the exocrine pancreas. Although they can develop metastasis, the prognosis is good. The aim of this study was to describe the characteristics of these tumours attended in our hospital. PATIENTS AND METHOD: All cases of SPN in the database of the Pathology Department between 1991 and 2010 were included. Age, sex, symptoms, type of surgery, pathologic and immunohistochemical characteristics, and clinical evolution were analyzed. RESULTS: Six cases were identified; all of them were women with a median age of 27.5 years. One patient presented haemoperitoneum, 2 abdominal pain and 3 were diagnosed incidentally. The most frequent localization was the pancreatic tail (n=4) and the median size was 7.7 cm. Four tumours were benign and 2 carcinomas. One of them had liver and lymph node metastases. Ki-67 proliferation index was low (1-3%). After a median follow-up of 33.5 months, all patients were alive and without evidence of relapse. CONCLUSION: SPNs occur in young women. In most cases surgical resection is curative. A low mitotic index confers a good prognosis and a long survival. PMID- 22036463 TI - [PFAPA syndrome: study of 10 cases]. AB - BACKGROUND AND OBJECTIVES: "PFAPA syndrome" is an autoinflammatory entity consisting of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis. Its etiology is unknown although a dysregulation in the control of the autoinflammatory response seems to play a role. Although a genetic origin is suspected, no specific mutation has been determined yet. Corticosteroids are the mainstay of the treatment during the acute attacks. However, in long-term follow up the role of tonsillectomy is controversial. PATIENTS AND METHODS: A retrospective study of the pediatric cases diagnosed with the PFAPA syndrome was performed in our center during the last 4 years. RESULTS: Ten patients were diagnosed with the syndrome who received corticosteroids as the only treatment with improvement and favourable prognosis. CONCLUSION: PFAPA syndrome is the most common periodic fever disorder described in childhood whose genetic background has not been yet clarified. Our contribution with 10 patients further supports the common existence of this entity and the need to keep it in mind when having recurrent fevers. PMID- 22036464 TI - [Treatment of psoriasis with anti-TNF drugs in human immunodeficiency virus infected patients]. PMID- 22036465 TI - Coenzyme Q10 enhances the anticonvulsant effect of phenytoin in pilocarpine induced seizures in rats and ameliorates phenytoin-induced cognitive impairment and oxidative stress. AB - Conventional antiepileptic drugs fail to adequately control seizures and predispose to cognitive impairment and oxidative stress with chronic usage in a significant proportion of patients with epilepsy. Coenzyme Q10 (CoQ10), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. To evaluate the neuroprotective effects of CoQ10 in rats against the observed oxidative stress during seizures induced by pilocarpine, and to study its interactions with the conventional antiepileptic drug phenytoin, two experiments were performed. Experiment 1 was conducted to test the effect of phenytoin, CoQ10, or both on seizure severity and oxidative markers in the pilocarpine model of epilepsy. Experiment 2 was conducted to test the effect of 2 weeks of chronic treatment with phenytoin, CoQ10, or both on oxidative markers and behavioral tests in rats. Overall, CoQ10 reduced the severity of pilocarpine-induced seizures and the severity of oxidative stress. Moreover, it potentiated the antiepileptic effects afforded by phenytoin treatment, with the potential safety and efficacy in ameliorating oxidative stress and cognitive impairment caused by chronic phenytoin therapy. Our findings strongly suggest that CoQ10 can be considered a safe and effective adjuvant to phenytoin therapy in epilepsy both to ameliorate seizure severity and to protect against seizure-induced oxidative damage by reducing the cognitive impairment and oxidative stress associated with chronic use of phenytoin. PMID- 22036466 TI - Internalizing disorders and psychosocial functioning in the context of successful epilepsy surgery in children: implications for a comprehensive approach and a global perspective of treatment. PMID- 22036467 TI - [The determinants of under-reporting occupational diseases. The case of mesothelioma]. AB - BACKGROUND: Despite widespread press coverage of the harm caused by the asbestos, 40% of mesothelioma patients still do not file claims for compensation as an occupational disease. We aimed at studying elements that influence the administrative procedure of compensation, in particular social classes and instruction level. METHODS: This was a statistical analysis of data from the French national survey program of mesothelioma designed to understand social determinants of reporting occupational illness. Data from a give administrative district were then submitted to a qualitative study using in-depth interviews of patients with suspected mesothelioma. Discourse analysis was then applied to the corpus of information collected. Content analysis grouped the data into themes. RESULTS: The statistical analyses tended to show that the higher the educational level, the less often patients filed claims for their occupational disease. Manual workers asked for compensation for their disease more often than executives. The interviews conducted with suspected mesothelioma patients suggest several factors explaining these findings. The process of reporting an occupational disease is often initiated by the primary care physician who informs the patient about the possible link with a previous occupation, explains the procedure and motivate the patient whose main preoccupation is to fight against the illness, and less so to become recognized as a victim. In this context, the physician plays a fundamental role, independently of the patient's social status. CONCLUSION: Those results throw new light on the complexity of the administrative procedure for reporting occupational diseases in France and highlights possible causes of underdeclaration reporting. Physician awarness of these causes might improve identification of links between occupation and disease and the transmission of adapted information to all concerned patients in order to fight more effectively against the disparities resulting from underreporting. PMID- 22036468 TI - Whole grain intake in relation to body weight: from epidemiological evidence to clinical trials. AB - This viewpoint aims to 1) review the available scientific literature on the relationship between whole grain consumption and body weight regulation; 2) evaluate the potential mechanisms whereby whole grain intake may help reduce overweight and 3) try to understand why epidemiological studies and clinical trials provide diverging results on this topic. All the prospective epidemiological studies demonstrate that a higher intake of whole grains is associated with lower BMI and body weight gain. However, these results do not clarify whether whole grain consumption is simply a marker of a healthier lifestyle or a factor favoring "per se" lower body weight. Habitual whole grain consumption seems to cause lower body weight by multiple mechanisms such as lower energy density of whole grain based products, lower glycemic index, fermentation of non digestible carbohydrates (satiety signals) and finally by modulating intestinal microflora. In contrast with epidemiological evidence, the results of few clinical trials do not confirm that a whole grain low-calorie diet is more effective in reducing body weight than a refined cereal diet, but their results may have been affected by small sample size or short duration of the intervention. Therefore, further intervention studies with adequate methodology are needed to clarify this question. For the time being, whole grain consumption can be recommended as one of the features of the diet that may help control body weight but also because is associated with a lower risk to develop type 2 diabetes, cardiovascular diseases and cancer. PMID- 22036470 TI - Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. AB - Newborns are colonized with an intestinal microbiota shortly after birth, but the factors governing the retention and abundance of specific microbial lineages are unknown. Nursing infants consume human milk oligosaccharides (HMOs) that pass undigested to the distal gut, where they may be digested by microbes. We determined that the prominent neonate gut residents, Bacteroides thetaiotaomicron and Bacteroides fragilis, induce the same genes during HMO consumption that are used to harvest host mucus glycans, which are structurally similar to HMOs. Lacto N-neotetraose, a specific HMO component, selects for HMO-adapted species such as Bifidobacterium infantis, which cannot use mucus, and provides a selective advantage to B. infantis in vivo when biassociated with B. thetaiotaomicron in the gnotobiotic mouse gut. This indicates that the complex oligosaccharide mixture within HMOs attracts both mutualistic mucus-adapted species and HMO adapted bifidobacteria to the infant intestine that likely facilitate both milk and future solid food digestion. PMID- 22036469 TI - Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. AB - Porphyromonas gingivalis is a low-abundance oral anaerobic bacterium implicated in periodontitis, a polymicrobial inflammatory disease, and the associated systemic conditions. However, the mechanism by which P. gingivalis contributes to inflammation and disease has remained elusive. Here we show that P. gingivalis, at very low colonization levels, triggers changes to the amount and composition of the oral commensal microbiota leading to inflammatory periodontal bone loss. The commensal microbiota and complement were both required for P. gingivalis induced bone loss, as germ-free mice or conventionally raised C3a and C5a receptor-deficient mice did not develop bone loss after inoculation with P. gingivalis. These findings demonstrate that a single, low-abundance species can disrupt host-microbial homeostasis to cause inflammatory disease. The identification and targeting of similar low-abundance pathogens with community wide impact may be important for treating inflammatory diseases of polymicrobial etiology. PMID- 22036472 TI - To improve maternity care in the United States, think midwives. PMID- 22036471 TI - Adsorption of methylene blue from aqueous solution by graphene. AB - Graphene was prepared using a modified Hummers' method. The physico-chemical properties of graphene were characterized by TEM, BET specific surface area, FTIR, Raman and XRD measurements. The effect factors including pH, contact time, temperature and dosage on the adsorption properties of methylene blue onto graphene were investigated. The experimental data of isotherm followed the Langmuir isotherm model better than the Freundlich model. The maximum adsorption capacity obtained from Langmuir isotherm equation at 293 K was 153.85 mg/g, indicating graphene is a good adsorbent for the adsorption of MB. The kinetic study illustrated that the adsorption of methylene blue onto graphene fit the pseudo second-order model. The thermodynamic parameters indicated that the adsorption of methylene blue onto graphene was an endothermic and spontaneous process. PMID- 22036474 TI - Induced abortion in Canada 1974-2005: trends over the first generation with legal access. AB - BACKGROUND: Canadian women currently entering menopause are the first generation with access to legal induced abortion throughout their reproductive years. STUDY DESIGN: Statistics Canada data from 1974 to 2005 on age-specific abortion and first-abortion rates were analyzed to determine the proportion of the cohort hypothetically and actually undergoing at least one induced abortion, as well as the age-specific trends. RESULTS: Among Canadian women who turned 45 years old in 2005, 31% had at least one abortion, with a median age at first abortion of 24 years. Since 1997, age-specific induced abortion rates overall and among teenagers have declined significantly, while rates among older women show less decline as age increases. Annually from 1974 to 2005, women aged 20-29 years account for 52% (SD 1.8%) of all abortions in Canada. CONCLUSIONS: Induced abortion is a common procedure experienced by nearly a third of Canadian women during their reproductive years. Consistently, half of all women accessing abortion are in their twenties. These findings suggest that Canadian women, particularly those in their twenties, experience a significant unmet need for effective contraception. PMID- 22036473 TI - Progestin-only contraception prevents bone loss in postpartum breastfeeding women. AB - BACKGROUND: There are an increase in bone loss during the first 6 months postpartum and a complete recovery postweaning. A few studies of steroid contraceptive use during this period provide some evidence towards protection of bone loss with progestin-only contraceptive methods. OBJECTIVE: The study was conducted to evaluate forearm bone mineral density (BMD) of breastfeeding postpartum women using nonhormonal and progestin-only contraceptive methods. STUDY DESIGN: A prospective cohort study of postpartum women had an analysis performed at 6 months postpartum correlating BMD with contraceptive use. Forearm BMD was measured 7-10 days, 3 months and 6 months postpartum. Eighty-two women were analyzed, comparing nonhormonal (54) and progestin-only (28) contraceptive methods. Information about breastfeeding duration, amenorrhea and body mass index was collected. RESULTS: Baseline characteristics of the study population showed no statistical differences between the groups. The median duration of breastfeeding for both groups was 183 days. A significant BMD decrease was observed for the nonhormonal group (p<.001); however, no statistical difference was detected for the progestin-only group. Body mass index, BMD at 7-10 days postpartum and total duration of breastfeeding were positively correlated with BMD at 6 months. CONCLUSIONS: Our findings suggest a preventive effect towards postpartum bone loss with progestin-only contraception in breastfeeding women. PMID- 22036475 TI - Trigeminal neuralgia related to arteriovenous malformation of the posterior fossa: three case reports and a review of the literature. AB - OBJECTIVE: To describe the rare association of trigeminal neuralgia (TGN) with a brain arteriovenous malformation (bAVM) of the posterior fossa. PATIENTS AND METHODS: This is a report of three patients presenting with TGN due to vascular compression by a bAVM of the posterior fossa, with emphasis on clinical presentation, diagnostic imaging, management and follow-up. Magnetic resonance imaging (MRI) was performed with sequences in thin slices in the same section plane using a 3D time of flight (TOF) and axial T2-weighted driven equilibrium (DRIVE) of the posterior fossa. RESULTS: No bleeding episodes were documented in the three patients. MRI and digital subtraction angiography (DSA) showed a posterior fossa bAVM with a nidus surrounding the trigeminal nerve, fed by arteries from the carotid and vertebrobasilar systems. Within a few days, medical treatment effectively alleviated the symptoms, with no more pain during follow ups at 6, 10 and 18months. No invasive treatment was performed because the bAVMs were considered to have a low risk of bleeding. CONCLUSION: TGN related to a bAVM can mimic classical TGN. MRI and DSA are the imaging methods of choice. Medical treatment remains the first line of therapy, but if that fails, multimodal invasive treatment may be an alternative for pain relief. PMID- 22036476 TI - Simulation of the human TMJ behavior based on interdependent joints topology. AB - The temporomandibular joint (TMJ) is one of the most important and complex joints of the body and its pathologies affect a great percentage of the human population. The simulation of the TMJ behavior during opening, closing and chewing movements can be very useful to the understanding of this articulation by physicians, helping them to prevent or fix problems due to accidents or diseases. This work proposes a model to simulate the human TMJ behavior based on the concept of two interdependent joints. The model was conceived using multimodal information acquired from CT and MRI images of a live person, as well as motion data acquired from this same person with a magnetic motion capture device. Simulation of movement of other TMJs, based on different morphology of bones and teeth, is obtained by adapting the regular captured motion data through collision detection and treatment methods. The proposed model was evaluated through image registration techniques by comparing our simulated results with real, captured motion data. We also validate the model showing how it can be used to predict TMJ behavior in the presence of different--normal or abnormal--bones and teeth morphologies. PMID- 22036478 TI - Training of child neurologists in the 21st century: overview. PMID- 22036479 TI - What the child neurologist should know at the conclusion of training: history taking, examination, and formulation (and a few other generalizations). AB - Taking of neurological history, performance of neurological examination, and the employment of these sets of information to properly formulate a neurological question constitute the most fundamantal skills of the neurologist. Intelligent facility with these skills must be required of every child neurologist at the completion of training. They will subsequently be refined upon the basis of experience and wider knowledge of neurology and neuroscience which will improve upon the initial level of facility. There are other habits of mind and approach that must also be expected to have been awakened and refined by the time that formal training has been completed. PMID- 22036480 TI - Neurology training for the child neurologist. AB - The training of the child neurologist in the fundamentals of neurology is discussed. Although the fundamentals of neurology are clearly necessary for the practice of child neurology, the breadth of the background necessary for the practice of child neurology depend on the interest, enthusiasm, and goals of the resident in question. Some of the issues involved in the design and implementation of the training curriculum will be considered. PMID- 22036477 TI - Maintenance of imaginal disc plasticity and regenerative potential in Drosophila by p53. AB - Following irradiation (IR), the DNA damage response (DDR) activates p53, which triggers death of cells in which repair cannot be completed. Lost tissue is then replaced and re-patterned through regeneration. We have examined the role of p53 in co-regulation of the DDR and tissue regeneration following IR damage in Drosophila. We find that after IR, p53 is required for imaginal disc cells to repair DNA, and in its absence the damage marker, gamma-H2AX is persistently expressed. p53 is also required for the compensatory proliferation and re patterning of the damaged discs, and our results indicate that cell death is not required to trigger these processes. We identify an IR-induced delay in developmental patterning in wing discs that accompanies an animal-wide delay of the juvenile-adult transition, and demonstrate that both of these delays require p53. In p53 mutants, the lack of developmental delays and of damage resolution leads to anueploidy and tissue defects, and ultimately to morphological abnormalities and adult inviability. We propose that p53 maintains plasticity of imaginal discs by co-regulating the maintenance of genome integrity and disc regeneration, and coordinating these processes with the physiology of the animal. These findings place p53 in a role as master coordinator of DNA and tissue repair following IR. PMID- 22036481 TI - Ataxia and the cerebellum. AB - Ataxia, an abnormality in the fine control of movement and posture, is a common neurologic sign in the pediatric population. While ataxia may be due to lesions in a variety of locations throughout the peripheral and central nervous systems, it is most commonly due to dysfunction of the cerebellum. It is critically important for child neurologists to recognize ataxia and to master its differential diagnosis because many of the diseases that induce ataxia in children are treatable and may require urgent attention. PMID- 22036482 TI - Pediatric patients with cerebral palsy or other developmental disabilities. PMID- 22036483 TI - Education of a child neurologist: epilepsy and electroencephalography. AB - Epilepsy is one of the most common disorders encountered in pediatric neurology. A well-trained child neurologist should have an understanding of the neurobiological causes of seizures, classification of seizures and epilepsy, etiologic evaluation, and treatment of both seizures and associated comorbid conditions. Electroencephalography (EEG) is an important diagnostic test in epilepsy, and child neurologists should be knowledgeable in the physiological basis of EEG and how to identify normal and abnormal patterns in neonates and children. PMID- 22036484 TI - A brief synopsis of the "why, what, and how" of teaching ethics to pediatric neurology trainees. PMID- 22036485 TI - Genetics and child neurology: what every trainee/resident should know. AB - The training of residents in child neurology varies from one center to another, being influenced to a large extent by the nature and volume of the clinical practice at a specific center and the expertise of the faculty. There is no doubt that there is an undercurrent of genetics in everything we do as child neurologists, sometimes explicit and sometimes implicit. In this article, we highlight a fundamental set of concepts, principles, methodologies, and learning tools/resources of which every child neurology trainee should have some knowledge. We may eventually arrive at a child neurology curriculum that might be continuously revised and maintained (perhaps through the Child Neurology Society) and serve as a template for individual training programs. PMID- 22036486 TI - Headache competencies in child neurology. AB - This is a proposal for suggested physician competencies in the diagnosis and treatment of children and adolescent patients with headaches. Headaches are common in childhood and occur in up to 10% of school-aged children and over 20% of female adolescents. Therefore, the appropriate recognition, evaluation, and treatment should be a high priority of training and maintenance of certification programs. PMID- 22036487 TI - Infectious diseases of the nervous system. AB - The curriculum for child neurology trainees should include information regarding the many infectious and post-infectious disorders that affect the developing nervous system. This article provides recommendations regarding the nature of the educational content and suggestions how this content can be provided to trainees. PMID- 22036488 TI - Noninfectious central nervous system inflammatory disorders. AB - Acute central nervous system (CNS) inflammation may occur as a monophasic illness or may represent the first attack of a chronic inflammatory disorder, such as multiple sclerosis, neuromyelitis optica, or CNS vasculitis. We review essential components of the initial assessment, diagnostic workup, acute and chronic management strategies, and research issues pertaining to children with CNS inflammatory diseases and suggest methods for these competencies to be attained during the course of child neurology residency training. PMID- 22036489 TI - Inborn errors of metabolism for child neurology residents. AB - Inborn errors of metabolism (IEMs) are individually rare, but collectively common, and impose a burden on affected individuals, their families and society that is disproportionate to their individual incidence and prevalence. Child neurologists should be able to recognize the possibility of an IEM as the cause of their patients' symptoms and signs, and utilize online and print resources to initiate an appropriate work up and referrals. The foundation of this knowledge is an understanding of the mechanisms of IEMs, coupled with a practical classification of the relevant diseases, and knowledge of the resources available to make diagnoses and devise treatment plans. They should also be prepared to manage affected children as part of a multidisciplinary team that draws on the skills of other professionals and community organizations. Because of rapid advances in diagnostic technology and the improving survival of children with IEMs, all child neurologists should anticipate caring for children and families with IEMs, and must acquire the ability to diagnose and manage these disorders as part of their residency training, recognizing that maintenance of this competence requires a commitment to life-long learning. PMID- 22036490 TI - Educating child neurologists about movement disorders. AB - The discipline of childhood movement disorders is an exciting new area of specialization within the field of pediatric neurology. Establishing a formal educational system is an ongoing challenge that should include the standardization of movement definitions, the development of a formal classification system for existing disorders, the adequate exposure of trainees to both common and rare disorders, and the ongoing formulation of topic guidelines and consensus papers. Specific suggestions and recommendations are provided for further discussion. PMID- 22036491 TI - Child neurologists as evaluators of developmental disorders. AB - Child neurologists are required to evaluate and care for an increasing number of children with developmental disorders; therefore they need to be familiar with the more prevalent ones, in particular the autism spectrum disorders which may masquerade as others. Their assessment needs to include a screening mental status evaluation and reviewing a recent definitive test of hearing in all children with defective speech. Neurologists' responsibility is to make sure that there is no likely underlying problem like epilepsy, neurologic, or genetic condition that requires specific medical intervention or genetic counseling. They need to discuss with the parents how deeply to test for neurologic, neuropsychologic, or genetic underlying causes in children with "idiopathic" developmental problem. There is no routine work-up, thus neurologists need to be aware of and to protect children from many almost certainly uninformative, expensive tests like EEGs, brain imaging, metabolic tests, and genetic micro-array unless there is a specific indication, or testing is being performed with parents' consent for research and paid for by research, not clinical, funds. Child neurologists-in training need to have observed psychologic/neuropsychologic testing so that they have at least a superficial understanding of the content, indications, and limitations of major tests. I do not recommend that child neurologists administer standardized tests or questionnaires, but they need to know enough about them to be able to judge their appropriateness and review recommendations with parents. Neurologists need to protect children from unnecessary testing, ineffective and in some cases potentially dangerous exploitative treatments. They must be aware of what legitimate therapies are likely to be offered, that early appropriate education is most effective long-term because it influences brain development and is superior to symptomatic pharmacotherapy. If pills are needed, child psychiatrists are likely to be better informed than neurologists and need to be consulted whenever medications familiar to neurologists are not adequately effective. PMID- 22036492 TI - Education of a child neurologist in neonatal neurology. AB - The newborn infant and the neonatal intensive care unit are areas in which there is great variability in the involvement of child neurology. As preterm birth rates continues to rise, with the associated long-term neurologic morbidities, and neuroprotective interventions become available for the newborn infant, a critical knowledge of neurology in the newborn is required for a well-trained child neurologist. PMID- 22036493 TI - What the child neurologist should know about neurocutaneous conditions. AB - At the completion of the general phase of neurological training, the child neurologist cannot be expected to have at the fingertips a comprehensive knowledge of the broad field and complex field of neurocutaneous disorders. The curiosity to seek out neurocutaneous features, especially where they may be relevant to a problem upon which a patient or family is consulting, is to be expected. So is acquaintance with clinical findings and neurological manifestations of certain conditions that assume particular importance because of they are particularly prevlaent or particularly serious. PMID- 22036494 TI - Educating the child neurologist about neuroimaging. AB - Training in child neurology is becoming increasingly technically oriented. Neuroimaging, in particular, has undergone massive expansion over the past few decades. By the end of training, it is important for trainees to be reasonably adept with magnetic resonance imaging, computed tomography scanning, positron emission tomography, single-photon emission computed tomography scanning, and cranial ultrasound. Trainees should understand the means by which images are acquired, the types of image contrast available, the risks inherent to each modality, the clinical setting in which a particular imaging method is useful, and the fundamentals of image interpretation. Training should include formal sessions in imaging basics as well as continuous exposure to imaging throughout clinical rotations. Trainees should be encouraged to evaluate all images from their patients, forming their own interpretation before reviewing them with attending neurologists and/or radiologists. PMID- 22036495 TI - Child neurology residency training in neuromuscular disorders. AB - The field of pediatric neuromuscular disorders provides rich training experiences in child neurology residency programs. Specific learning objectives include skills in examination and assessment, familiarity with muscle and nerve studies, and indications for biopsies. This review also specifies which neuromuscular disorders are most important to cover within the resident's scope of knowledge, as well as the relationship of this field to the core competencies of residency training. Appropriate settings for inclusion of these skills in child neurology residency programs are suggested. PMID- 22036496 TI - Neuro-oncology training for the child neurology resident. PMID- 22036497 TI - What the child neurologist should know about the visual system. AB - The visual system provides an important and highly sensitive opportunity to localize and diagnose neurological diseases. Within the context of the enormous sybject of neuro-ophthalmology there are fundamentals that should be known at the completion of training by the child neurologist. Upon the basis of this information the child neurologist may increase and refine sophistication through the course of an ensuing career. PMID- 22036498 TI - The developing human brain: what the emerging pediatric neurologist needs to know. AB - The developing human brain is a remarkable tissue. Embryonic and fetal brain growth is largely genetically controlled. Environmental factors become increasingly important with advancing development. The young pediatric neurologist who masters a little fundamental neuroanatomy, developmental neuroanatomy, and developmental neuropathology will be able to interpret neuroimages and abnormal development because he or she understands the structural changes in growth failures, hemorrhages, acquired lesions, white matter abnormalities, vascular disease and malformations, ventriculomegaly, tumors, infectious disease, common malformations, degenerative and demyelinative diseases, toxic, and metabolic diseases. PMID- 22036499 TI - Education of the child neurologist: pediatric neurocritical care. AB - Neurocritical care (NCC) is now an essential field in child neurology that requires dedicated training. NCC applies the basic principles of neuroresuscitation to all situations, integrates this with modern technology. and emphasizes that brain protection is not limited to the intensive care unit. We outline the essential competencies needed and how to obtain these. PMID- 22036500 TI - Pediatric residency preceding child neurology training. AB - Training in child neurology requires formal training in other aspects of pediatrics. This pediatrics training affords the ability to obtain a developmentally appropriate history and physical examination at all stages of childhood and adolescence and to provide anticipatory guidance to children and families of all developmental ages; the ability to identify and respond appropriately to emergent, urgent, and/or life-critical need for medical and/or psychosocial intervention on behalf of children and/or their families; the ability to identify and provide for appropriate medical and psychosocial services and supports for children and families affected by chronic and/or fatal diseases; and the ability to identify and respond appropriately to nonneurologic manifestations of risk factors for or harbingers of neurologic diseases or conditions. In this context, it also allows the trainee to hone skills in communication, counseling, teaching, and critical thinking, all of which are important for the effective practice of child neurology. PMID- 22036501 TI - Education of a child neurologist: developmental neuroscience relevant to child neurology. AB - Developmental neuroscience is increasingly relevant to clinical child neurology, and study of advances in neurobiology, neurochemistry and neurogenetics should be part of the curriculum of residency training. The profile of synaptic development is especially relevant to neurodevelopmental disorders such as autism, Fragile X syndrome, and early epileptic encephalopathies. This knowledge is increasingly being translated into therapies for previously untreatable disorders. PMID- 22036502 TI - Training issues pertaining to sleep medicine and child neurology. AB - Co-morbid sleep disorders are quite common in Child Neurology. Formal training in the field of sleep medicine and routine attention to sleep-wake function in clinical practice enhances the ability of the child neurologist to deliver comprehensive care. PMID- 22036503 TI - Education of the child neurologist: traumatic brain injury. AB - As traumatic brain injury is among the most common causes of pediatric mortality and neurologic morbidity, the well-trained child neurologist should have a solid foundation of the pathogenesis of traumatic brain injury and be competent in the acute and chronic management of children and adolescents who experience a traumatic brain injury. This article outlines the training goals and core knowledge of traumatic brain injury that should be attained by those training in child neurology by the completion of their formal training. PMID- 22036504 TI - Thymoquinone accelerates new bone formation in the rapid maxillary expansion procedure. AB - OBJECTIVE: The aim of this study was to evaluate the effect of systemic thymoquinone (TQ) in a rat rapid maxillary expansion (RME) study. DESIGN: Thirty two Wistar albino rats were divided into 4 equal groups: only-expansion (OE), expansion plus TQ (TQ1 group, TQ given to the rats during their nursery phase and during the expansion and retention period), expansion plus TQ (TQ2 group, TQ given to the rats only during the retention period), and control group (no procedure done). Expansion appliances were placed on the maxillary incisors of all animals for 5days. The appliance was deactivated during the 12day retention period. The rats were sacrificed at the end of the retention period. Histomorphometric evaluation was carried out in order to compare the number of osteoclasts, osteoblasts, and capillaries, as well as the intensities of inflammatory cells, and new bone formation amongst the groups. RESULTS: New bone formation, number of capillaries and the ratio of intensities of inflammatory cells in maxillary sutures was higher in the TQ groups than in the other groups. Statistical analysis also demonstrated that osteoblast and osteoclast numbers were also highest in the TQ1 group. CONCLUSION: Histomorphometric analysis demonstrated that systemic use of thymoquinone may be effective in accelerating new bone formation in the RME procedure and that TQ may be beneficial in preventing relapse following the RME procedure. PMID- 22036505 TI - Cone Beam CT using motion-compensated algebraic reconstruction methods with limited data. AB - Cone Beam Computed Tomography (CBCT) is widely used in radiation therapy for verifying treatment areas, since it provides three-dimensional image reconstruction of those tumour regions under inspection. However, organ motion is problematic during the scanning process, it causes motion artefacts on the CBCT image and can lead to mispositioning for the subsequent treatment. Moreover, patient dose is also considerable and there is a need for methods which yield acceptable image quality with as few X-ray images as possible. Although methods have been developed to handle limited projection data, such as the Algebraic Reconstruction Technique (ART); Simultaneous ART (SART); and Ordered-Subset SART (OS-SART), this study applied motion compensation to these reconstruction techniques. Root Mean Square Error (RMSE) of image is calculated to study the convergence of reconstructed images compared with the truth image. When motion was applied to a phantom and the motion compensation was used to account for the motion, the results showed that motion compensation improved the quality of CBCT image, when compared to uncompensated images. Furthermore, the experiments suggested that minimising phase error, for breathing models, was more important than minimising amplitude error. PMID- 22036506 TI - The E3 ubiquitin-ligase HACE1 catalyzes the ubiquitylation of active Rac1. AB - Rac1 small GTPase controls essential aspects of cell biology and is a direct target of numerous bacterial virulence factors. The CNF1 toxin of pathogenic Escherichia coli addresses Rac1 to ubiquitin-proteasome system (UPS). We report the essential role of the tumor suppressor HACE1, a HECT-domain containing E3 ubiquitin-ligase, in the targeting of Rac1 to UPS. HACE1 binds preferentially GTP bound Rac1 and catalyzes its polyubiquitylation. HACE1 expression increases the ubiquitylation of Rac1, when the GTPase is activated by point mutations or by the GEF-domain of Dbl. RNAi-mediated depletion of HACE1 blocks the ubiquitylation of active Rac1 and increases GTP-bound Rac1 cellular levels. HACE1 antagonizes cell isotropic spreading, a hallmark of Rac1 activation, and is required for endothelial cell monolayer invasion by bacteria. Together, these data establish the role of the HACE1 E3 ubiquitin-ligase in controlling Rac1 ubiquitylation and activity. PMID- 22036507 TI - Outcome and efficacy of a transobturator polypropylene mesh kit in the treatment of anterior pelvic organ prolapse. AB - OBJECTIVE: To report the efficacy and complications of anterior pelvic organ prolapse (POP) repair with mesh placed through the transobturator route (Perigee system; AMS, Minnetonka, MN, USA). METHODS: In total, 198 women with anterior POP grade II or higher according to the POP Quantification (POP-Q) system were treated with the Perigee procedure. The primary outcome was defined as anterior POP grade I or lower at 12 months' follow-up. The secondary outcomes included the incidences of perioperative, mesh-related, short-term, and long-term postoperative complications. RESULTS: The cure rate was 92.9% overall and 90.6% among women who had previously undergone a hysterectomy or a traditional anterior colporrhaphy. The mean POP-Q Aa and Ba values were significantly improved after the procedure (Aa 2.2 cm [0.0 to 3.0 cm] versus -2.1cm [-3.0 to -1.2 cm]; Ba -2.5 cm [-1.0 to 4.2 cm] versus -2.2 cm [-5.5 to -1.0 cm]; P<0.001). Vaginal or bladder erosions were observed in 3 patients. Other short- and long-term complications were infrequent and not statistically significant. CONCLUSION: The Perigee procedure is effective in the treatment of anterior POP and does not have serious complications even among women with previous hysterectomy or traditional anterior colporrhaphy. PMID- 22036508 TI - Fatal mitral valve endocarditis following a Papanicolaou test. PMID- 22036509 TI - Characterization of colorectal symptoms in women with vesicovaginal fistulas. AB - OBJECTIVE: To characterize colorectal symptoms in women with a history of an obstetric vesicovaginal fistula (VVF). METHODS: Patients under evaluation with a VVF during two 2-week surgical service trips to Evangel Hospital VVF Center in Jos, Nigeria, in 2010 were assessed for symptoms of fecal incontinence (FI) using the Vaizey and Colorectal-Anal Impact (CRAIQ) questionnaires. Women with rectovaginal fistulas were excluded. Each participant's impression of overall health was assessed using a visual analog scale (VAS) from 0 (poor) to 15 (excellent). A study nurse translated questionnaires into native languages. RESULTS: The mean age of the 83 women included was 29 years. Three women (3.6%) reported FI and 42 (50.6%) reported constipation. All of the women with FI reported that it affected their quality of life on the CRAIQ. Average VAS score was 10.8 overall and 6.8 for women with FI. CONCLUSION: In this population of women with VVF but no rectovaginal fistulas, we found a low prevalence of fecal incontinence and a high prevalence of constipation. Despite significant pelvic floor trauma resulting in VVF, the majority of patients appeared to have an intact bowel continence mechanism. PMID- 22036510 TI - Pregnancy outcome in early-onset severe pre-eclampsia in Trinidad. PMID- 22036511 TI - Attitudes of married women left behind in rural areas of China toward people living with HIV/AIDS. PMID- 22036512 TI - Puerperal and menstrual bleeding patterns with different types of contraceptive device fitted during elective cesarean delivery. AB - OBJECTIVE: To evaluate the impact of a copper-containing intrauterine contraceptive device (IUCD) and the levonorgestrel-releasing intrauterine system (IUS) on puerperal and menstrual bleeding when fitted intraoperatively during scheduled elective cesarean. METHODS: Participants were allocated to 3 groups: cesarean with no device inserted; IUCD inserted during cesarean; and IUS inserted during cesarean. RESULTS: There was significantly shorter and lighter puerperium in the IUS group (20.2 +/- 7.7 days and 3.1 +/- 1.6 pads/day) than in the IUCD (33.4 +/- 9.5 days and 4.9 +/- 2.4 pads/day) and the control (27.0 +/- 11.4 days and 4.9 +/- 2.3 pads/day) groups (P<0.012 and P<0.0001, respectively). At the end of puerperium, mean duration of amenorrhea was significantly longer in the IUS group than in the IUCD and control groups (P<0.0001). Menstrual periods were longer and heavier in the IUCD group than in the control group but the difference was not significant (P>0.07). In the IUS group, menstrual periods were significantly shorter and lighter than in the other groups (P<0.0001). CONCLUSION: Intrauterine system fitting at the time of elective cesarean is associated with significant reductions in the duration and amount of puerperal blood loss, as well as a high incidence of amenorrhea and lighter periods thereafter. PMID- 22036513 TI - Clinical outcomes associated with surgical treatment of endometrioma coupled with resection of the posterior broad ligament. AB - OBJECTIVE: To evaluate clinical outcomes associated with the resection of both endometrioma and posterior broad ligament (PBL) among women with PBL adhesion associated with endometrioma. METHODS: Between January 2007 and December 2009 at the Villanova Hospital, Florence, Italy, a prospective trial was conducted on 99 consecutive patients with unilateral or bilateral endometrioma who underwent laparoscopic ovarian cystectomy by a stripping technique and homolateral PBL resection where PBL adhesion was associated with endometrioma. The prevalence of PBL adhesion and endometriosis, the association between PBL endometriosis and pain, and the recurrence of endometrioma and pain were evaluated. All data were analyzed with Prism software. RESULTS: Among 124 endometriomas treated by concomitant PBL resection, the PBL was not affected by adhesions in only 2% of patients. PBL endometriosis was superficial in 36 (29.5%) and deep in 86 (70.5%) of the histologic preparations; deep endometriosis correlated with preoperative pain. At 1-year follow-up, endometrioma had recurred in 7 patients; the main symptom reported was mid-cycle pain (24 patients, 24%; P=0.0007). CONCLUSION: Ovarian endometriosis was often (98%) associated with PBL endometriosis; deep endometriosis of PBL correlated with pain symptoms. Although PBL resection increased the incidence of mid-cycle pain, it was associated with low recurrence of endometrioma. PMID- 22036514 TI - Focus on phosphodiesterase inhibitors for the treatment of erectile dysfunction in older men. AB - BACKGROUND: Phosphodiesterase type 5 inhibitors (PDEIs) are the drugs of choice for the medical management of erectile dysfunction independent of the etiology of the disorder. OBJECTIVE: This review focuses on specific aspects of clinical use of PDEIs in older men with erectile dysfunction. METHODS: An electronic search of MEDLINE was conducted for articles published between January 1990 and January 2011 using the terms erectile dysfunction and PDEIs and limited to articles in English, humans, and males aged >=45 years. The search was also conducted in EMBASE using the same search criteria for literature indexed between 1990 and 2010. RESULTS: A total of 1341 articles were identified. Of these, ~91 were selected for this review. Sildenafil, vardenafil, and tadalafil are considered equally effective for erectile dysfunction, but they differ in some ways. Tadalafil's 36-hour duration of action allows for repeated sexual intercourse without the need to take additional medication in some patients, which is distinctly different from the shorter-acting sildenafil and vardenafil. Unlike tadalafil, the rate and extent of oral absorption of sildenafil and vardenafil are reduced by consumption of high-fat meals. Although headache, flushing, and rhinitis occur with all 3 PDEIs, cyanopsia is more common with sildenafil and vardenafil, and back pain is more common with tadalafil. Approximately 40% to 50% of patients who initially fail to respond to PDEIs can be salvaged with education and up-titration of dosing. PDEIs can be used in addition to antihypertensive medications in patients with well-controlled essential hypertension without producing clinically significant hypotension. Use of PDEIs in patients with cardiovascular disease is guided by the recommendations of the Second Princeton Consensus Conference. For the management of lower urinary tract symptoms due to benign prostatic hyperplasia, PDEIs may reduce obstructive voiding symptoms, but they do not increase urinary flow rate. CONCLUSION: PDEIs are effective for erectile dysfunction and well tolerated in older men. PMID- 22036515 TI - Requirements for immune recognition and processing of factor VIII by antigen presenting cells. AB - Generation of inhibitory antibodies upon repeated FVIII infusion represents a major complication in hemophilia care. Professional antigen presenting cells (APCs) are crucial for orchestration of humoral immune responses. APCs are capable of internalizing soluble as well as particulate antigens through various mechanisms resulting in loading of antigen-derived peptides on MHC class I or II for presentation to T cells. This review highlights how FVIII is recognized and processed by APCs. The significance and contribution of candidate receptors involved in FVIII uptake by APC are discussed. Recent findings defining the repertoire of FVIII peptides presented on MHC class II are addressed. Studies in murine models of hemophilia A suggest that modulation of APC function can reduce inhibitor formation. Based on this we anticipate that modulation of FVIII uptake by APCs may yield novel therapeutic approaches for treatment or prevention of inhibitor formation in patients with hemophilia A. PMID- 22036517 TI - Postoperative pain trajectories in chronic pain patients undergoing surgery: the effects of chronic opioid pharmacotherapy on acute pain. AB - For 2 weeks following surgery, 55 patients with preexisting chronic pain (CP) reported daily postoperative pain with movement and at rest. Of these, 30 CP patients used opioid pharmacotherapy for CP management and 25 did not. We modeled pain resolution in each patient using a linear fit so that each patient yielded 2 scores for each pain rating: 1) an intercept, or initial level of pain, immediately after surgery; and 2) a slope, or rate of pain resolution. The patients not using opioid pharmacotherapy had a mean pain with movement intercept of 5.4 and a slope of -.20, while the patients using opioid pharmacotherapy had a significantly higher mean intercept of 7.68 (P = .001) and a slope of -.21, sustaining higher pain levels over days. The opioid pharmacotherapy patients had the same rate of pain resolution as the other CP patients, and both groups resolved their pain more slowly than normal surgery patients. Preexisting CP may predispose a patient undergoing surgery to a slower rate of postoperative pain resolution. Chronic pain patients who use opioids share this predisposition but in addition, they are at risk for markedly higher postoperative pain across the entire pain resolution trajectory. PERSPECTIVE: This is an observational rather than a randomized controlled study, and as such is less definitive. Nonetheless, these findings are consistent with those of animal studies showing that prolonged exposure to opioids can produce opioid-induced hyperalgesia. Patients with opioid pharmacotherapy for chronic pain who undergo surgery merit special attention for acute pain management. PMID- 22036516 TI - Excess risk of temporomandibular disorder associated with cigarette smoking in young adults. AB - Evidence suggests that the effect of cigarette smoking on chronic pain is stronger in younger than older adults. This case-control study investigated whether age modified an effect of smoking on temporomandibular disorder (TMD) in 299 females aged 18 to 60 years. It also investigated the extent to which this relationship was explained by psychological profile, inflammatory response, and allergy. Cases were defined using the Research Diagnostic Criteria for Temporomandibular Disorders based on clinical examination. Psychological profile was evaluated using standardized instruments. Inflammatory response was evaluated with 11 cytokines isolated in plasma. History of allergy conditions was self reported. Odds ratios (ORs) for the effect of smoking were calculated using binary logistic regression. Stratified analyses and the likelihood ratio test examined effect modification by smoking. Compared with nonsmokers, ever smokers aged <30 years had higher odds of TMD (OR = 4.14, 95% CI: 1.57, 11.35) than older adults (OR = 1.23, 95% CI: .55, 2.78) (P (effect modification) = .038). Adjustment for psychological profile, cytokines, and history of allergy-like conditions attenuated the effect by 45% to statistical nonsignificance. The main finding was reproduced with secondary analyses of 2 nationally representative surveys of adults conducted in the US and Australia. PERSPECTIVE: This study showed that smoking was associated with TMD risk in females, but only in young adulthood. It replicated this finding in 2 nationally representative surveys of females in the US and Australia. Findings may alert clinicians to recognize that smoking is a concern for TMD in younger female patients. PMID- 22036518 TI - Twenty-nine cases of invasive aspergillosis in neutropenic patients. AB - INTRODUCTION: Invasive aspergillosis is a life-threatening infectious complication in hematological patients undergoing immunosuppressive chemotherapy. PATIENTS AND METHODS: We report 29 cases of invasive aspergillosis diagnosed in the Sousse Farhat Hached hospital Hematology unit, Tunisia, between 2002 and 2010. RESULTS: The most frequent disease (65.5%) was acute myeloid leukemia. All patients were severely neutropenic (<500/mm(3), mean duration=27 days). Pulmonary invasive aspergillosis was suggested in 28 (96.5%) cases. The most frequent respiratory signs were cough (64.3%), chest pain (53.6%), and hemoptysis (50%). The chest X-ray showed suggestive lesions in 60.7% of cases. CT scans revealed nodules with cavitation in 65% of cases, a halo sign in 20% of cases, and nodules in 15% of cases. Galactomannan antigenemia was positive in 88%, mycological examination positive in 51.6%, and seroconversion was noted in 35.7% of the cases. Invasive pulmonary aspergillosis was classified, according to EORTC/MSG criteria, as probable in 26 cases, possible in one case, and proven in one case. Aspergillus flavus was the dominant species in pulmonary invasive aspergillosis accounting for 73.7% of isolates. Extrapulmonary involvement was suggested in 39.3% of cases, the most frequent were sinusitis and brain abscess. Primary cutaneous aspergillosis was observed in one case. The overall mortality rate was 64.2%; the 12-week survival rate was 71.4%. CONCLUSION: Our results are correlated to published data. A. flavus was the most frequent species in our region. PMID- 22036520 TI - Legionella wadsworthii pneumonia: gram stain usefulness. PMID- 22036521 TI - Health economic evaluation in complementary medicine: development within the last decades concerning local origin and quality. AB - OBJECTIVES: This evaluation investigates characteristics of health economics evaluations in CAM. Particular emphasis is paid to differences regarding continental origin and time of publication of investigations. METHODS: Database searches to identify potential studies were carried out in Medline (via Pubmed), the Cochrane Central Register of Controlled Trials 1st Quarter 2010, the Cochrane Database of Systematic Reviews 2005 to January 2010, the Cochrane Methodology Register 1st Quarter 2010, the Database of Abstracts of Reviews of Effects 1st Quarter 2010, Health Technology Assessment (via OVID) and CAMbase. Data were screened, extracted and the methodological quality of the underlying publications was assessed. Univariate statistical analyses were carried out and Classification and Regression Tree (CART) analysis was performed. RESULTS: One hundred and forty three studies were included in this review, 43 of which were randomised trials. Of all included studies 56% were carried out in primary care settings and 54% chose the perspective of health care provider/health insurance. When the study characteristics were stratified for the "year of publication" (before versus in/after 2002), locally significant differences were found for study setting (Chi square p=0.014) and methodological quality (Mann/Whitney p=0.014). Furthermore, studies from America differed from those conducted in Europe with respect to the field of CAM (p<0.001, Chi-square). There were also differences in trial settings as the majority of European studies was carried out in primary care settings (n=54; 70%), whereas American studies had a broader scope with only 24 studies (42%) in the field of primary care. The CART analyses confirmed the findings of the univariate analysis. CONCLUSION: Differences in healthcare systems were mirrored by the observed differences in CAM related health economic evaluations. Basic requirements for reporting and conducting clinical trials ought to be met in more studies evaluating health economics. Such evaluations need to include validated quality of life estimates and preferably report the use of incremental cost effectiveness or net health benefit estimates. PMID- 22036519 TI - Listeria monocytogenes encephalitis in France. AB - PURPOSE: The authors had for aim to describe the characteristics of listeriosis encephalitis patients enrolled in a national study. METHODS: Listeria monocytogenes was identified as the forth etiology of encephalitis, in a prospective study in France, in 2007. We analyzed 12 cases with confirmed listeriosis (seven with rhombencephalitis, five with encephalitis) and compared them with encephalitis of other etiologies and with listeriosis encephalitis, mandatorily notified during the same year. RESULTS: L. monocytogenes strains were genoserotyped as IVb (n=6), IIa (n=3), and IIb (n=3). Cerebrospinal fluid (CSF) median protein level was 2.5g/L and the median WBC counts was 367cells/mm(3). Among twelve patients, seven patients had ongoing comorbidities. The case fatality rate during hospitalization was 50%. Patients presenting with listeriosis enrolled in the study did not differ from those reported to the mandatory surveillance system according to their demographical characteristics and comorbidities. They were older, presented more frequently with cancer, or were more often under corticosteroid treatment than patients presenting with encephalitis due to other etiologies. CONCLUSIONS: Neurolisteriosis has a poor prognosis, thus it should be considered early in patients presenting with encephalitis to improve its management. PMID- 22036522 TI - The use of Complementary and Alternative Medicine in pregnancy: data from the Avon Longitudinal Study of Parents and Children (ALSPAC). AB - OBJECTIVES: To report the frequency of Complementary and Alternative Medicine (CAM) use by a population of pregnant women in the UK. DESIGN: Four postal self completion questionnaires completed at 8, 12, 18 and 32 weeks' gestation provided the source of CAMs used. Questions asked for written descriptions about the use of any treatments, pills, medicines, ointments, homeopathic medicines, herbal medicines, supplements, drinks and herbal teas. SETTING: An observational, population-based, cohort study of parents and children of 14,541 pregnant women residing within the former county of Avon in south-west England. Data was available for 14,115 women. RESULTS: Over a quarter (26.7%; n=3774) of women had used a CAM at least once in pregnancy, the use rising from 6% in the 1st trimester to 12.4% in the 2nd to 26.3% in the 3rd. Herbal teas were the most commonly reported CAM at any time in pregnancy (17.7%; n=2499) followed by homeopathic medicine (14.4%; n=2038) and then herbal medicine (5.8%; n=813). The most commonly used herbal product was chamomile used by 14.6% of women, the most commonly used homeopathic product was Arnica used by 3.1% of women. Other CAMs (osteopathy, aromatherapy, acupuncture/acupressure, Chinese herbal medicine, chiropractic, cranial sacral therapy, hypnosis, non-specific massage and reflexology) accounted for less than 1% of users. CONCLUSIONS: CAM use in pregnancy, where a wide range of CAMs has been assessed, has not been widely reported. Studies that have been conducted report varying results to this study (26.7%) by between 13.3% and 87% of pregnant women. Survey results will be affected by a number of factors namely the inclusion/exclusion of vitamins and minerals, the timing of data collection, the country of source, the number of women surveyed, and the different selection criteria of either recruiting women to the study or of categorising and identifying a CAM treatment or product. PMID- 22036523 TI - The effects of Lyprinol((r)) on delayed onset muscle soreness and muscle damage in well trained athletes: a double-blind randomised controlled trial. AB - OBJECTIVES: The aim of the study was to determine if Lyprinol((r)) is effective in reducing pain, indicators of inflammation and muscle damage, and in turn improving performance in well trained athletes suffering from delayed onset muscle soreness (DOMS). DESIGN: A double blind randomised placebo controlled trial. SETTING: Twenty well trained male volunteers, matched by VO(2max) were randomly assigned to consume 200mg of Lyprinol((r)) or an indistinguishable placebo daily for 8 weeks prior to a downhill treadmill running episode designed to induce DOMS. MAIN OUTCOME MEASURES: Performance measures (Kin-Com, counter movement and squat jump), pain assessments (visual analogue scale, algometer) and blood analyses (Interleukin-1, Interleukin-6, Interleukin-10, tumour necrosis factor-alpha, C-reactive protein, myoglobin, creatine kinase) were assessed at 7 time points over 5 days (pre, post, 4, 24, 48, 72 and 96h after the downhill run). RESULTS: No statistically significant differences were identified in any parameters between the active and placebo groups at any time point. CONCLUSION: After 2 months ingestion of Lyprinol((r)) at the currently recommended dosage (200mg/day) and a demanding eccentric exercise intervention, Lyprinol((r)) did not convincingly affect DOMS and indicators of muscle damage. PMID- 22036524 TI - Efficacy of Traditional Chinese Herbal Medicine in the management of female infertility: a systematic review. AB - OBJECTIVES: To assess the effect of Traditional Chinese Herbal Medicine (CHM) in the management of female infertility and on pregnancy rates compared with Western Medical (WM) treatment. METHODS: We searched the Medline and Cochrane databases and Google Scholar until February 2010 for abstracts in English of studies investigating infertility, menstrual health and Traditional Chinese Medicine (TCM). We undertook meta-analyses of (non-)randomised controlled trials (RCTs) or cohort studies, and compared clinical pregnancy rates achieved with CHM versus WM drug treatment or in vitro fertilisation (IVF). In addition, we collated common TCM pattern diagnosis in infertility in relation to the quality of the menstrual cycle and associated symptoms. RESULTS: Eight RCTs, 13 cohort studies, 3 case series and 6 case studies involving 1851 women with infertility were included in the systematic review. Meta-analysis of RCTs suggested a 3.5 greater likelihood of achieving a pregnancy with CHM therapy over a 4-month period compared with WM drug therapy alone (odds ratio=3.5, 95% CI: 2.3, 5.2, p<0.0001, n=1005). Mean (SD) pregnancy rates were 60+/-12.5% for CHM compared with 32+/-10% using WM drug therapy. Meta-analysis of selected cohort studies (n=616 women) suggested a mean clinical pregnancy rate of 50% using CHM compared with IVF (30%) (p<0.0001). CONCLUSIONS: Our review suggests that management of female infertility with Chinese Herbal Medicine can improve pregnancy rates 2-fold within a 4 month period compared with Western Medical fertility drug therapy or IVF. Assessment of the quality of the menstrual cycle, integral to TCM diagnosis, appears to be fundamental to successful treatment of female infertility. PMID- 22036525 TI - The effectiveness of music listening in reducing depressive symptoms in adults: a systematic review. AB - OBJECTIVES: We aim to review trials of the effectiveness of music listening in reducing depressive symptoms in adults, and identify areas requiring further study. BACKGROUND: Little is known about the efficacy of music listening in the mediation of depressive symptoms. METHODS: We systematically search 9 databases and reviewed 17 studies included randomized controlled and quasi-experimental trails of music listening in reducing depressive symptoms in adults. The Joanna Briggs Institute-Meta Analysis of Statistics Assessment and Review Instrument was used for quality assessment of included studies. RESULTS: Music listening over a period of time helps to reduce depressive symptoms in the adult population. Daily intervention does not seem to be superior over weekly intervention and it is recommended that music listening session be conducted repeatedly over a time span of more than 3weeks to allow an accumulative effect to occur. CONCLUSIONS: All types of music can be used as listening material, depending on the preferences of the listener. So, it is recommended that the listeners are given choices over the kind of music which they listen to. There is a need to conduct more studies, which replicate the designs used in the existing studies that met the inclusion criteria, on the level of efficacy of music listening on the reduction of depressive symptoms for a more accurate meta-analysis of the findings and reflect with greater accuracy the significant effects that music has on the level of depressive symptoms. PMID- 22036526 TI - Comment on the "Assessment of a traditional acupuncture therapy for chronic neck pain: a pilot randomized controlled study". PMID- 22036527 TI - Phenotypic and genetic diversity among intestinal spirochaetes (genus Brachyspira) in free-living wild mallards (Anas platyrhynchos) sampled in southern Sweden. AB - Brachyspira spp. are anaerobic intestinal spirochaetes that colonize vertebrates. Some species cause enteric diseases in pigs, chickens and possibly in humans, whereas others display a commensual relationship with their hosts. The aims were to investigate the prevalence among colonized free-living wild mallards (Anas platyrhynchos) of three enteropathogenic Brachyspira spp., and to describe the biodiversity of Brachyspira spp. isolates. Isolates from 150 birds were screened by PCR for 3 pathogenic Brachyspira spp., and 35 isolates from 20 mallards, 4 pigs and 1 chicken were subjected to phenotypic tests, 9 diagnostic PCRs, sequencing of the 16S rRNA and NADH oxidase (nox) genes, phylogenetic analysis and nox gene restriction enzyme analysis in silico. Of the 150 birds, 47%, 33% and 11% were positive by PCR for Brachyspira pilosicoli, Brachyspira intermedia and Brachyspira hyodysenteriae, respectively. Thirty-one characterized isolates were provisionally identified as B. intermedia, Brachyspira alvinipulli, "Brachyspira pulli", or B. pilosicoli, whereas 4 were of indeterminate species affiliation. Many isolates were phylogenetically related to isolates from livestock. Isolates identified by PCR as B. pilosicoli displayed particularly high biodiversity. Up to five different Brachyspira genotypes were found from the same bird. Sequencing of amplicons from isolates that displayed ambiguous results as judged from PCR and phenotyping showed that several diagnostic PCRs were non specific. Nox gene restriction enzyme analysis in silico correctly identified 2 of 34 characterized isolates. A culture technique based on filtration that produced uncontaminated spirochaete isolates was described. The results show that mallard intestines support a high degree of biodiversity among Brachyspira spp. PMID- 22036529 TI - Long-term age of acquisition effects in famous name processing. AB - The age of acquisition (AoA) effect refers to the processing advantage that words, objects, and people learnt earlier in life hold over those acquired later. We explored the long-term effects of AoA on performance, using naturally occurring famous names, acquired by participants cumulatively over three decades. We manipulated AoA by selecting celebrities who had first become known to our participants in the 1960s, 1970s, or 1980s and explored the effects of age by testing participants aged in their 40s, 50s, or 60s. Seventy-two participants made push-button 'Yes-No' familiarity decision judgements to the printed names of celebrities. We found a significant AoA effect. A linear increase in reaction time was uncovered, with the participants being fastest to respond to the 1960s celebrities, followed by those from the 1970s, and being slowest to respond to celebrities from the 1980s. There was no age * AoA interaction, although the AoA effect was most pronounced in the oldest participant group. Our data demonstrate the long-term persistent influence of AoA on processing speed. Moreover, they indicate that the effects of AoA are much more subtle than simply reflecting a difference between the earliest acquired stimuli in a processing domain and all later acquired items. PMID- 22036528 TI - Galectins: guardians of eutherian pregnancy at the maternal-fetal interface. AB - Galectins are multifunctional regulators of fundamental cellular processes. They are also involved in innate and adaptive immune responses, and play a functional role in immune-endocrine crosstalk. Some galectins have attracted attention in the reproductive sciences because they are highly expressed at the maternal-fetal interface, their functional significance in eutherian pregnancies has been documented, and their dysregulated expression is observed in the 'great obstetrical syndromes'. The evolution of these galectins has been linked to the emergence of eutherian mammals. Based on published evidence, galectins expressed at the maternal-fetal interface may serve as important proteins involved in maternal-fetal interactions, and the study of these galectins may facilitate the prediction, prevention, diagnosis, and treatment of pregnancy complications. PMID- 22036530 TI - Immediate effect of nimmo receptor tonus technique on muscle elasticity, pain perception, and disability in subjects with chronic low back pain. AB - OBJECTIVE: Objectives of this study were to (1) quantify the immediate effect of Nimmo technique on muscle elasticity, pain perception, and disability and (2) evaluate comparative effectiveness of treating all primary and secondary trigger points (TrPs) vs primary TrP only. METHODS: Fourteen chronic low back pain subjects recruited from a chiropractic college were tested in this within-day repeated-measures design study. Gluteus medius containing a prominent TrP was indented for 4 sessions using a mechanoacoustic indentor system. A finite element optimization method extracted hyperelastic material constants of the gluteus medius. Load-deformation response on a standardized block was simulated. Area under the load-deformation curve from 0% to 25% deformation (A(FE)) and force at 25% deformation (F(FE)) were determined. No treatment was applied between the first and second sessions. Only the primary TrP in gluteus medius was treated between the second and third sessions. Full Nimmo treatment was used between the third and fourth sessions requiring treatment of all primary and secondary TrPs. The A(FE), F(FE), tissue thickness, subjective pain, and Oswestry Disability Index were compared between sessions. RESULTS: After full Nimmo treatment, A(FE) and F(FE) were significantly smaller than baseline (P = .021 and .027, respectively) and focal TrP treatment only (P = .003 and .001, respectively). The changes accompanied concomitant improvement in subjective pain and disability. It appears that focal TrP treatment resolves TrP, but full Nimmo treatment further reduces electrogenic spasm. CONCLUSIONS: Immediate effect of a single full Nimmo treatment appears to reduce muscle tone, subjective pain, and disability and be more beneficial than focal TrP treatment. PMID- 22036531 TI - Relationship between interpretation and accuracy of the upper limb neurodynamic test 1 in carpal tunnel syndrome. AB - OBJECTIVE: This prospective diagnostic test study evaluated the relationship between interpretation criteria and accuracy of the Upper Limb Neurodynamic Test 1 (ULNT1) in the diagnosis of carpal tunnel syndrome. METHODS: A blind comparison with a reference criterion of typical clinical presentation and abnormal median nerve conduction was used. All subjects were first tested with nerve conduction studies and then with ULNT1. Each examiner was blinded to the results collected by the other examiners. RESULTS: We analyzed 47 subjects and 84 limbs. Considering ULNT1 as positive in the presence of reproduction of symptoms only in the thumb or lateral 2 fingers, we estimated sensitivity to be equal to 40% (95% confidence interval [CI], 0.256-0.564), specificity 79.59% (95% CI, 0.664-0.885), positive predictive value 58.33% (95% CI, 0.388-0.755), negative predictive value 65% (95% CI, 0.524-0.758), positive likelihood ratio 1.96 (95% CI, 1.275-3.012), and negative likelihood ratio 0.7538 (95% CI, 0.490-1.159). Considering the increase of symptoms with contralateral or decrease of symptoms with ipsilateral cervical side bending as mandatory positivity criterion, specificity improved, but sensitivity decreased. CONCLUSION: Our investigation suggests that the reproduction of symptoms in the thumb or lateral 2 fingers of the affected arm during ULNT1 has weak diagnostic accuracy for carpal tunnel syndrome. PMID- 22036532 TI - Effects of manual therapy on craniofacial pain in patients with chronic rhinosinusitis: a case series. AB - OBJECTIVE: Chronic rhinosinusitis (CRS) is thought to develop through an inadequate drainage of nasal and sinus secretions and perpetuated by local mechanical and autonomic nervous system factors. Manual therapy may have an effect on these factors providing symptomatic relief of CRS symptoms. The purpose of this prospective case series was to report the results of manual therapy on a set of patients with craniofacial pain and a diagnosis of CRS. METHODS: Fourteen consecutive patients presenting with a primary report of craniofacial pain and a diagnosis CRS completed self-report questionnaires including the Sinonasal Assessment Questionnaire, Rhinosinusitis Task Force, visual analog scale for craniofacial pain, and pressure pain threshold over 4 sinus points on the face. Patients were seen once a week for 7 consecutive weeks and completed all outcome measures at baseline and subsequent weekly sessions. They received manual therapy interventions only on the second, third, and fifth weekly sessions. RESULTS: No significant changes in outcome measures were observed from baseline to 1 week, where no intervention was applied. Significant improvements were observed on all outcome measures (Ps <= .015) for pre- and post-first treatment session, as well as from baseline to 7 weeks (Ps < .001). All patients exhibited a significant decrease in craniofacial pain and increased pressure pain thresholds and reported less severity of their symptoms. CONCLUSION: Patients with craniofacial pain and CRS who were treated with manual therapy demonstrated improvements in all outcome measures only after each treatment session. Our results suggest that manual therapy treatment could be considered as an appropriate alternative treatment of CRS. PMID- 22036533 TI - Acidic beta-mannanase from Penicillium pinophilum C1: Cloning, characterization and assessment of its potential for animal feed application. AB - The beta-mannanase gene, man5C1, was cloned from Penicillium pinophilum C1, a strain isolated from the acidic wastewater of a tin mine in Yunnan, China, and expressed in Pichia pastoris. The sequence analysis displayed the gene consists of a 1221-bp open reading frame encoding a protein of 406 amino acids (Man5C1). The deduced amino acid sequence of Man5C1 showed the highest homology of 57.8% (identity) with a characterized beta-mannanase from Aspergillus aculeatus belonging to glycoside hydrolase family 5. The purified rMan5C1 had a high specific activity of 1035U mg(-1) towards locust bean gum (LBG) and showed highest activity at pH 4.0 and 70 degrees C. rMan5C1 was adaptable to a wide range of acidity, retaining >60% of its maximum activity at pH 3.0-7.0. The enzyme was stable over a broad pH range (3.0 to 10.0) and exhibited good thermostability at 50 degrees C. The K(m) and V(max) values were 5.6 and 4.8mgmL( 1), and 2785 and 1608MUmolmin(-1)mg(-1), respectively, when LBG and konjac flour were used as substrates. The enzyme had strong resistance to most metal ions and proteases (pepsin and trypsin), and released 8.96mgg(-1) reducing sugars from LBG in the simulated gastric fluid. All these favorable properties make rMan5C1 a promising candidate for use in animal feed. PMID- 22036534 TI - The impact of rotator cuff tendinopathy on proprioception, measuring force sensation. AB - BACKGROUND: The impact of rotator cuff tendinopathy and related impingement on proprioception is not well understood. Numerous quantitative and qualitative changes in shoulder muscles have been shown in patients with rotator cuff tendinopathy. These findings suggest that control of force might be affected. This investigation wants to evaluate force sensation, a submodality of proprioception, in patients with rotator cuff tendinopathy. METHODS: Thirty-six patients with rotator cuff tendinopathy and 30 matched healthy subjects performed force reproduction tests to isometric external and internal rotation to investigate how accurately they could reproduce a fixed target (50% MVC). Relative error, constant error, and force steadiness were calculated to evaluate respectively magnitude of error made during the test, direction of this error (overshoot or undershoot), and fluctuations of produced forces. RESULTS: Patients significantly overshoot the target (mean, 6.04% of target) while healthy subjects underestimate the target (mean, -5.76% of target). Relative error and force steadiness are similar in patients with rotator cuff tendinopathy and healthy subjects. Force reproduction tests, as executed in this study, were found to be highly reliable (ICC 0.849 and 0.909). Errors were significantly larger during external rotation tests, compared to internal rotation. CONCLUSION: Patients overestimate the target during force reproduction tests. This should be taken into account in the rehabilitation of patients with rotator cuff tendinopathy; however, precision of force sensation and steadiness of force exertion remains unaltered. This might indicate that control of muscle force is preserved. PMID- 22036535 TI - Use of an O-arm intraoperative computed tomography scanner for closed reduction of posterior sternoclavicular dislocations. PMID- 22036536 TI - Reconstruction of massive uncontained glenoid defects using a combined autograft allograft construct with reverse shoulder arthroplasty: preliminary results. AB - BACKGROUND: This report documents our experiences with a new technique for reconstructing massive uncontained defects of the glenoid with reverse total shoulder arthroplasty. MATERIALS AND METHODS: We use a modified deltopectoral approach to perform the combined allograft-autograft construct glenoid reconstruction. We make use of a peripherally seated cortical allograft acting as a sleeve bushing to provide a stable ring under compression in which to house impacted cancellous autograft centrally for early incorporation and in-growth with the long-peg Aequalis (Tornier, Saint-Ismier Cedex, France) reverse total shoulder arthroplasty baseplate. RESULTS: Our case series now comprises 10 patients with postoperative follow-up of up to 36 months. We report the first 5 patients here, all of whom have more than 12 months of follow-up. Computed tomography scanning demonstrates incorporation of the graft as early as 6 months. None of these patients have had loosening, implant failures, dislocations, periprosthetic fractures, or infections. One patient sustained an acromial stress fracture that was successfully treated nonoperatively, and 1 patient has nonprogressive grade I notching. CONCLUSION: The hybrid graft glenoid reconstruction is a useful and versatile technique in the setting of massive uncontained defects of the glenoid and permits the implantation of a reverse total shoulder arthroplasty. We believe this technique is reproducible and uses materials that are both readily available and familiar. PMID- 22036537 TI - In vivo and 3-dimensional functional anatomy of the anterior bundle of the medial collateral ligament of the elbow. AB - BACKGROUND: Although the anterior bundle of the medial collateral ligament (AMCL) is a critical stabilizer of the elbow joint, little information exists on in vivo and 3-dimensional functional anatomy of the AMCL. The purposes of this study were to investigate in vivo changes in the length of the AMCL during elbow flexion and to clarify the 3-dimensional functional anatomy of the AMCL. METHODS: We created 3-dimensional models of the AMCL and bones from computed tomography data of 4 healthy elbows in 5 different elbow positions. The AMCL was subdivided into 9 ligaments. We calculated changes in lengths of ligaments during flexion and related ligament origins to the axis of rotation of the elbow joint. RESULTS: There were 4 uniquely configured isometric ligaments, where their origins aligned broadly along the course of the axis of rotation in the coronal plane. The medially originating ligaments inserted on the posterior portion of the tubercle of the coronoid process, whereas the laterally originating ligaments inserted on its anterior portion. There were 5 non-isometric ligaments, 3 of which had origins proximal to the axis and became taut only in extension and the other 2 having origins distal to the axis and becoming taut only in flexion. CONCLUSIONS: Isometric ligaments within the AMCL do not originate from a narrow area; rather, they originate from a broader area that extends more medially in the coronal plane than previously thought, which explains how the AMCL reconciles isometricity and robustness. The proximal and distal ligaments act as checkreins that work only at the limits of elbow motion. PMID- 22036538 TI - Diagnostic accuracy of five orthopedic clinical tests for diagnosis of superior labrum anterior posterior (SLAP) lesions. AB - BACKGROUND: The clinical diagnosis of a superior labral anterior posterior (SLAP) tear is extremely challenging. Most studies that advocate selected tests have errors in study design or significant bias, or both. The purpose of this study was to identify the diagnostic utility of the Active Compression/O'Brien's test, Biceps Load II test, Dynamic Labral Shear test (O'Driscoll's test), Speed's test, and the Labral Tension test when diagnosing isolated SLAP lesions (SLAP-only) and a SLAP lesion with concomitant disorders (eg, rotator cuff tear), as stand-alone and clustered tests, with diagnostic confirmation by arthroscopic surgery. MATERIALS AND METHODS: This diagnostic accuracy study was a case-based, case control design that included 87 individuals with variable shoulder pathology. RESULTS: Of the 5 tests, only the Biceps Load II test demonstrated utility in identifying patients with a SLAP-only lesion, with a positive predictive value of 26 (95% confidence limits [CL], 18, 31), negative predictive value of 93 (95% CL, 84, 97), positive likelihood ratio of 1.7 (95% CL, 1.1, 2.6), and negative likelihood ratio of 0.39 (95% CL, 0.14, 0.91). No tests demonstrated diagnostic utility when diagnosing any SLAP lesion, including those with concomitant diagnoses. No clusters demonstrated better diagnostic accuracy than stand-alone findings. CONCLUSION: There are a number of potential reasons for the poor utility in the 5 test findings. The heterogeneous sample included patients with a variety of shoulder disorders. The study was organized using very strict methodologic controls that should reduce the risk of bias, which normally overinflates the accuracy of a specific tool. The findings may truly reflect the stand-alone, diagnostic utility of the 5 tests, suggesting when used alone provides little usefulness toward decision making of the diagnostic clinician. PMID- 22036539 TI - Arthroscopic treatment of septic arthritis of the elbow. AB - HYPOTHESIS: Septic arthritis of the elbow is a serious orthopedic concern associated with high morbidity and mortality rates, traditionally treated with open exposure of the elbow joint. This study was performed to describe the outcome of arthroscopic treatment of septic elbow arthritis. METHODS: From May 2000 through January 2008, 12 patients with septic elbow arthritis were treated arthroscopically at the Mayo Clinic, Rochester, Minnesota, a large medical center. We reviewed the patients' medical records concerning variables such as history and clinical findings, previous elbow history, surgical procedure, cultured organism, and follow-up. Using the Oxford Elbow Score and the Mayo Elbow Score, we examined current level of pain, function, and social-psychological aspects. Six patients died before initiation of this study and were therefore only studied retrospectively. RESULTS: Septic elbow arthritis without pre existing elbow problems shows excellent outcomes after arthroscopic treatment, with scores for absence of pain, function, social-psychological well-being, and range of motion of 97.9%, 100%, 95.8%, and 100%, respectively. When elbows were treated arthroscopically within 2 days after the onset of clinical symptoms suggesting bacterial elbow arthritis, maximum scores of 100% were noted for all aspects. Positive elbow history before infection and reoperation were associated with poor outcome scores, with 62.5%, 85.4%, and 50% for absence of pain, function, and social-psychological well-being, respectively. CONCLUSION: Septic elbow arthritis occurs often in the debilitated, immunocompromised patient. Arthroscopic intervention is a reasonable alternative to open treatment. In this small series, the acutely septic elbow was successfully treated in the majority of patients, although the overall patient mortality rate remains high. PMID- 22036540 TI - Assessment of glenoid inclination on routine clinical radiographs and computed tomography examinations of the shoulder. AB - BACKGROUND: Accurate assessment of glenoid inclination is of interest for a variety of conditions and procedures. The purpose of this study was to develop an accurate and reproducible measurement for glenoid inclination on standardized anterior-posterior (AP) radiographs and on computed tomography (CT) images. MATERIALS AND METHODS: Three consistently identifiable angles were defined: Angle alpha by line AB connecting the superior and inferior glenoid tubercle (glenoid fossa) and the line identifying the scapular spine; angle beta by line AB and the floor of the supraspinatus fossa; angle gamma by line AB and the lateral margin of the scapula. Experimental study: these 3 angles were measured in function of the scapular position to test their resistance to rotation. Conventional AP radiographs and CT scans were acquired in extension/flexion and internal/external rotation in a range up to +/-40 degrees . Clinical study: the inter-rater reliability of all angles was assessed on AP radiographs and CT scans of 60 patients (30 with proximal humeral fractures, 30 with osteoarthritis) by 2 independent observers. RESULTS: The experimental study showed that angle alpha and beta have a resistance to rotation of up to +/-20 degrees . The deviation from neutral position was not more than +/-10 degrees . The results for the inter rater reliability analyzed by Bland-Altman plots for the angle beta fracture group were (mean +/- standard deviation) -0.1 +/- 4.2 for radiographs and -0.3 +/ 3.3 for CT scans; and for the osteoarthritis group were -1.2 +/- 3.8 for radiographs and -3.0 +/- 3.6 for CT scans. CONCLUSION: Angle beta is the most reproducible measurement for glenoid inclination on conventional AP radiographs, providing a resistance to positional variability of the scapula and a good inter rater reliability. PMID- 22036541 TI - Clinical features of partial anterior bursal-sided supraspinatus tendon (PABST) lesions. AB - BACKGROUND: We characterized partial anterior and bursal supraspinatus tendon (PABST) lesions and compared their clinical features, postoperative functional scores, and healing rate with full-thickness rotator cuff tears (FTRCTs) and small FTRCTs. MATERIALS AND METHODS: There were 31 PABST lesions (6.2%), 392 FTRCTs, and 32 small FTRCTs among 495 shoulders with rotator cuff disorders. The mean patient age was 52.7 years in the PABST group, 60.1 years in the FTRCT group, and 56.9 years in the small FTRCT group. Functional and clinical variables were compared between the groups, and cuff healing was evaluated with computed tomography arthrography or ultrasonography. RESULTS: The mean patient age was statistically lower, the mean symptom duration was shorter, and trauma was more frequent in the PABST group compared with the FTRCT and small FTRCT groups. Coronal acromial spurs were found more frequently in the PABST group than in the FTRCT group. In all groups, range of motion, visual analog scale for pain, and functional scores improved continuously throughout the follow-up. There were 2 unhealed cuffs (10.5%) in the PABST group, 72 (35.6%) in the FTRCT group (P = .146), and 5 (25%) in the small FTRCT group (P = .238). CONCLUSIONS: We characterized PABST lesions that may be overlooked because of their peculiar location in the far anterolateral insertional section of the supraspinatus tendon at the bursal side. PABST lesions usually occur in younger patients, and trauma is frequently associated with acute symptom onset. Surgical treatment was effective for pain reduction and functional improvement. PMID- 22036542 TI - K-wire position in tension-band wiring technique affects stability of wires and long-term outcome in surgical treatment of olecranon fractures. AB - BACKGROUND: Tension-band wiring (TBW) has been accepted as the treatment of choice for displaced olecranon fractures. The aim of this study was to examine the effect of K-wire position on instability of the K-wires in relation to local complications and radiological and clinical long-term outcome. METHODS: We reviewed the early follow-up of 59 patients (mean age, 60 years) who underwent TBW osteosynthesis for displaced olecranon fractures. Follow-up information was available from medical records and radiographs. The main outcome measurements were proximal migration of the wires, gap, step, range of motion, and complications. Long-term follow-up included 21 patients (mean age, 58 years). Follow-up was available from a clinical visit and a radiograph. Visual Analogue Scale (VAS), Mayo Elbow Performance Score (MEPS), Disabilities of the Arm Shoulder and Hand (DASH), EuroQol-5D (EQ-5D), and Broberg and Morrey osteoarthritis scores were obtained. RESULTS: Seventy-eight percent of the patients treated with intramedullary K-wires were found to have instability of K wires, compared to 36% in the patients treated with transcortical K-wires. Patients with instability of the K-wires tend to develop osteoarthritis more often. There is a better functional outcome in patients where the osteosynthetic material is removed. CONCLUSION: Instability of K-wires after TBW is more common after intramedullary placement of the wires resulting in proximal migration of the K-wires and gap appearance. There was a tendency of more osteoarthritis in the group of patients where instability of K-wires was identified. We would recommend the use of transcortical placed wires, as well as to have a low threshold in removing the implants. PMID- 22036543 TI - Humeral component retroversion in reverse total shoulder arthroplasty: a biomechanical study. AB - BACKGROUND: Reverse total shoulder arthroplasty offers pain relief and functional improvement for patients with rotator cuff-deficient shoulders. The purpose of this study was to determine the optimal amount of humeral retroversion for this prosthesis. MATERIALS AND METHODS: Six cadaveric shoulders underwent computed tomography (CT) imaging and were then dissected of soft tissues, except for their tendinous attachments. A reverse total shoulder arthroplasty was implanted in 0 degrees , 20 degrees , 30 degrees , and 40 degrees of retroversion, and the shoulders were mounted on a simulator to determine the muscle forces required to achieve 30 degrees and 60 degrees of scaption. CT images were converted into 3 dimensional models, and the amount of internal and external rotation was determined with computer modeling at various scaption angles. RESULTS: No differences were found in the forces required for 30 degrees or 60 degrees of scaption for any muscle, at any retroversion. With increasing retroversion, more impingement-free external rotation was obtained, with a concomitant decrease in the amount of internal rotation. Above 60 degrees , the humerus was allowed to rotate around the glenosphere unencumbered. CONCLUSIONS: Increasing retroversion did not affect the muscle force requirements for scaption across the shoulder. Placing the humeral component in 0 degrees to 20 degrees of retroversion allows maximum internal rotation with the arm at the side, a movement that is required for daily activities. This limits external rotation with the arm at the side, but has no effect on external rotation with the arm elevated. PMID- 22036544 TI - Infraspinatus fatigue during resisted arm elevation with isometric contraction: an electromyographic study. AB - BACKGROUND: Various forms of resistance are used in rotator cuff training programs. However, the muscular activity of the infraspinatus during arm elevation has not been clarified in detail. We aimed to evaluate infraspinatus fatigue during resisted arm elevation in various positions. METHODS: The dominant (right) shoulders of 39 healthy subjects were examined. Average mean power frequency shifts of the infraspinatus and deltoid were evaluated electromyographically when the subjects performed isometric contractions equivalent to 30% of the maximal voluntary isometric contraction force for 60 s during 90 degrees arm elevation in the sagittal and scapular planes, prone and side-lying external rotations, and repeated side-lying external rotation exercise. Further, the arm-elevation force was measured before and after the repeated external rotation exercise. Analysis of variance and paired t tests were used for statistical analyses; differences at P < .05 were considered significant. RESULTS: The infraspinatus was fatigued easily during resisted arm elevation in the sagittal plane compared with the scapular plane (P < .01). Comparisons of sagittal-plane elevation with side-lying and prone external rotations revealed no significant differences in the fatigue levels. The arm elevation force after the repeated external rotations was significantly decreased in the sagittal plane compared with the scapular plane (P < .01). CONCLUSION: In clinical settings, this data may be helpful in knowing how to helpful to protect the infraspinatus after surgical repair. Therefore, therapeutic exercise regimes with resisted arm elevation should avoid infraspinatus overfatigue in the sagittal plane in the early postoperative period. PMID- 22036545 TI - Moderate to large engaging Hill-Sachs defects: an in vitro biomechanical comparison of the remplissage procedure, allograft humeral head reconstruction, and partial resurfacing arthroplasty. AB - BACKGROUND: The management of engaging Hill-Sachs defects (HSD) is controversial. The purpose of this study was to biomechanically compare 3 treatment strategies. MATERIALS AND METHODS: Eight specimens were tested on a shoulder simulator. The protocol involved testing 2 unrepaired HSD (30% and 45%), which were then treated with remplissage, humeral head allograft (HHA), and partial resurfacing arthroplasty (PRA). Stability (defect engagement and glenohumeral stiffness) and range of motion (ROM) were measured. RESULTS: All 30% and 45% HSDs engaged and dislocated. Remplissage and HHA effectively prevented engagement in all specimens; however, 62% of PRA engaged. No repair exhibited stiffness significantly greater than intact, but 30% and 45% remplissage produced a 74% and 207% increase, respectively, and were significantly greater than the unrepaired states (P <= .047). Stiffness results for HHA and PRA closely matched those of intact. In adduction, remplissage reduced internal-external ROM compared with both defects (P <= .01), but only 30% remplissage caused a significant decrease compared with intact (P = .049). In abduction, all repairs reduced ROM compared with HSD (P <= .04), but none compared with intact (P >= 0.05). In extension, remplissage had significantly less ROM than either HHA or PRA (P <= .02). CONCLUSION: All procedures improved stability; however, unlike remplissage, results from HHA and PRA closely resembled intact. Remplissage (30% and 45%) improved stability and eliminated engagement but caused reductions in ROM. HHA and PRA re-established intact ROM, but PRA could not fully prevent engagement. The effects of each technique are not equivalent and further studies are required. PMID- 22036546 TI - Effect of lateral offset center of rotation in reverse total shoulder arthroplasty: a biomechanical study. AB - BACKGROUND: Lateral offset center of rotation (COR) reduces the incidence of scapular notching and potentially increases external rotation range of motion (ROM) after reverse total shoulder arthroplasty (rTSA). The purpose of this study was to determine the biomechanical effects of changing COR on abduction and external rotation ROM, deltoid abduction force, and joint stability. MATERIALS AND METHODS: A biomechanical shoulder simulator tested cadaveric shoulders before and after rTSA. Spacers shifted the COR laterally from baseline rTSA by 5, 10, and 15 mm. Outcome measures of resting abduction and external rotation ROM, and abduction and dislocation (lateral and anterior) forces were recorded. RESULTS: Resting abduction increased 20 degrees vs native shoulders and was unaffected by COR lateralization. External rotation decreased after rTSA and was unaffected by COR lateralization. The deltoid force required for abduction significantly decreased 25% from native to baseline rTSA. COR lateralization progressively eliminated this mechanical advantage. Lateral dislocation required significantly less force than anterior dislocation after rTSA, and both dislocation forces increased with lateralization of the COR. CONCLUSION: COR lateralization had no influence on ROM (adduction or external rotation) but significantly increased abduction and dislocation forces. This suggests the lower incidence of scapular notching may not be related to the amount of adduction deficit after lateral offset rTSA but may arise from limited impingement of the humeral component on the lateral scapula due to a change in joint geometry. Lateralization provides the benefit of increased joint stability, but at the cost of increasing deltoid abduction forces. PMID- 22036547 TI - Functional and radiographic medium-term outcome evaluation of the Humerus Block, a minimally invasive operative technique for proximal humeral fractures. AB - BACKGROUND: Conservative treatment of severe displacement of proximal humeral fracture fragments yields bad functional results, but open operative techniques have a high risk of avascular necrosis of the humeral head. We performed a medium term outcome evaluation of the Humerus Block (Synthes, Oberdorf, Switzerland), a minimally invasive technique used in selected patients with proximal humeral fractures, to investigate the functional and radiographic outcome. MATERIALS AND METHODS: Of 47 patients operated on with the Humerus Block, 34 with a minimum follow-up of 30 months and a mean follow-up of 4 years and 4 months, were invited for interview, radiographic evaluation, and functional analysis by the Constant, Disabilities of Arm, Shoulder and Hand (DASH) and the University of California, Los Angeles (UCLA) scorings. Paired t test was used to investigate equivalence of the geometric mean scores of the trauma and control arm, for the scores of the functional analyses, and for the scores for mobility of the shoulder. RESULTS: Scorings and clinical examination showed that 85% of shoulder function and motion were preserved compared with the control arm. Radiographic evaluation showed very good healing and positioning of the fracture fragments, and only 10% developed avascular necrosis of the humeral head. CONCLUSIONS: With very satisfied patients; good clinical, functional, and radiographic outcomes; a short hospital stay; few complications; a reduced cost of implant; and a low incidence of avascular necrosis, this technique is a valuable alternative for operative treatment of proximal humeral fractures. PMID- 22036548 TI - Massive acromioclavicular ganglionic cyst treated with excision and allograft patch of acromioclavicular region. PMID- 22036549 TI - Kinematic analysis of dynamic shoulder motion in patients with reverse total shoulder arthroplasty. AB - BACKGROUND: Reverse total shoulder arthroplasty (rTSA) has been used to treat patients with irreparable rotator cuff dysfunction. Despite the proven clinical efficacy, there is minimal information regarding the underlying changes to the shoulder kinematics associated with this construct. Therefore, we sought to examine the kinematics of dynamic shoulder motion in patients with well functioning rTSA. METHODS: We tested 12 healthy subjects and 17 patients with rTSA. All rTSA patients were able to elevate their arms to at least 90 degrees and received the implant as the primary arthroplasty at least 6 months before testing. On average, the rTSA patients elevated their arms to 112 degrees +/- 12 degrees (mean +/- SD) and reported an American Shoulder and Elbow Surgeons outcome score of 90.6 +/- 6.3. A 3-dimensional electromagnetic motion capture device was used to detect the dynamic motion of the trunk, scapula, and humerus during bilateral active shoulder elevation along the sagittal, scapular, and coronal planes. RESULTS: In both healthy and rTSA shoulders, the majority of the humeral-thoracic motion was provided by the glenohumeral motion. Therefore, the ratio of glenohumeral to scapulothoracic (ST) motion was always greater than 1.62 during elevation along the scapular plane. In comparison to healthy subjects, however, the contribution of ST motion to overall shoulder motion was significantly increased in the rTSA shoulders. This increased contribution was noted in all planes of shoulder elevation and was maintained when weights were attached to the arm. CONCLUSION: Kinematics of the rTSA shoulders are significantly altered, and more ST motion is used to achieve shoulder elevation. PMID- 22036550 TI - The effects of pH, bromide and nitrite on halonitromethane and trihalomethane formation from amino acids and amino sugars. AB - In this study, the effects of pH, bromide and nitrite on the formation of halonitromethanes (HNMs) and trihalomethanes (THMs) from eight amino acids (glycine, alanine, serine, cysteine, aspartic acid, glutamic acid, lysine and histidine) and four amino sugars (glucosamine, galactosamine, N-acetylglucosamine and N-acetylneuraminic acid) were examined for chlorination and ozonation followed by chlorination. During ozonation-chlorination, two amino acids, glycine and lysine, exhibited distinctly higher HNM formation than the other compounds. The formation of HNMs was higher at pH 8 than 6. Glycine and lysine also produced higher levels of THMs than the other compounds at pH 8. The presence of nitrite resulted in an increase in HNM formation. The presence of bromide increased the HNM formation, especially brominated HNM species. Bromine incorporation factors of trihalogenated HNMs were higher than those of THMs. For chlorination alone, HNM levels were about the detection limit (4 nM or 0.7 MUg L(-1)) at pH 6 and 8, and in the presence of bromide or nitrite. Amino acids and amino sugars tested, except glycine and lysine, showed relatively low levels of THM (~15 MUg L(-1)) formation. PMID- 22036551 TI - Peroxymonosulfate-Co(II) oxidation system for the removal of the non-ionic surfactant Brij 35 from aqueous solution. AB - The non-ionic surfactant Brij 35 was effectively removed from concentrated aqueous solution by the peroxymonosulfate/Co(II) system, using oxone (2KHSO(5).KHSO(4).K(2)SO(4)) as a source of peroxymonosulfate. At pH=2.3 and initial Brij 35 concentration in the range 680-2410 mg L(-1), 86-94% removal was achieved after 24 h, using Co(II)=15 MUM and oxone=5.9 mM. The effectiveness of removal did not change when initial pH was in the range 2.3-8.2. After five subsequent additions of Co(II) and oxone to the solution, COD and TOC removals increased up to 64% and 33%, respectively. Radical quenching tests confirmed that sulfate radical was the dominant radical species in the system. The main identified by-products from surfactant degradation were: (a) low molecular weight organic acids; (b) aldehydes and formates with shorter ethoxy chain than Brij 35; (c) alcohol ethoxylates carrying hydroxyl groups bonded to ethoxy chain. By products identification allowed to hypothesize the pathways of Brij 35 degradation. PMID- 22036552 TI - Bioaccumulation, depuration and biotransformation of 4,4'-dibromodiphenyl ether in crucian carp (Carassius auratus). AB - Polybrominated diphenyl ethers (PBDEs) are extensively used as a class of flame retardants and have become ubiquitous environmental pollutants. Significant biotransformation of some PBDEs via reductive debromination has been observed. However, little is known about the fate of lower brominated BDEs in fish. In this study, the tissue distribution, excretion, depuration and biotransformation of 4,4'-dibromodiphenyl ether (BDE 15) were investigated in crucian carp (Carassius auratus) which were exposed to spiked water solution at different concentrations for 50d, followed by a 14-d depuration period. Bioaccumulation parameters were calculated and the results showed that BDE 15 was mainly concentrated in the gill and liver. In particular, five biotransformation products of BDE 15 in carp were identified using GC-MS/MS. Besides two debrominated metabolites, three of the metabolites were mono-OH-BDE 15, diOH-BDE 15 and bromophenol. Our results unequivocally suggested that BDE 15 oxidation did occur via the formation of hydroxylated (OH-) metabolites in crucian carp exposed in vivo. These findings will be useful for determination of the metabolic pathways of PBDEs in freshwater fish, especially about their oxidation metabolism. PMID- 22036553 TI - [Management of eyelid tumors: general considerations]. AB - Despite the fact that the majority of eyelid tumors are benign, proper management in daily practice requires detection of the malignant ones. Several clinical criteria are usually proposed to support or reject a hypothesis of malignancy; however, most are of limited reliability. In any case of doubt, outpatient biopsy is recommended, so as to establish the correct diagnosis and formulate the most appropriate treatment plan. In all facial malignancies, the first (and absolutely mandatory) consideration is control of the cancer. Then, restoration of eyelid function can be addressed, in the following order: protection of the globe by complete dynamic eyelid closure and opening, visual function (and prevention of possible deprivation amblyopia) by insuring a clear visual axis, correction of the tear film, efficient lachrymal drainage, and only then the role of the eyelids in facial expression and esthetics. For most malignant eyelid tumors, the best assurance of complete excision is obtained by extemporaneous examination of the resection margins by frozen section (by Mohs' micrographic surgery techniques, or a variation thereof). Currently, advancement and transposition flaps, possibly in combination with tarso-conjunctival or skin grafts, are the most utilised techniques. Despite the lack of histological verification, new treatment modalities, including topical chemotherapy, photodynamic therapy and cryotherapy, may provide interesting treatment options, particularly in collaboration with the dermatologist. PMID- 22036554 TI - A breath of fresh air in lung regeneration. AB - Enhancing the ability of the lungs to regenerate following injury could revolutionize the treatment of a wide range of different diseases. In this issue, Kumar et al. (2011) and Ding et al. (2011) dissect the cellular and molecular mechanisms of murine lung regeneration following injury and provide insights into the basic biology of the organ with implications for development of future therapeutic approaches. PMID- 22036555 TI - A gutsy way to grow: intestinal stem cells as nutrient sensors. AB - Adult tissues can rapidly and reversibly change size to adapt to environmental and behavioral influences. In this issue, O'Brien et al. (2011) demonstrate that fly intestinal stem cells alter their division patterns in response to food availability to drive organ growth. PMID- 22036556 TI - You AhR what you eat: linking diet and immunity. AB - The aryl hydrocarbon receptor (AhR) is responsible for the toxic effects of environmental pollutants such as dioxin, but little is known about its normal physiological functions. Li et al. (2011) now show that specific dietary compounds present in cruciferous vegetables act through the AhR to promote intestinal immune function, revealing AhR as a critical link between diet and immunity. PMID- 22036557 TI - Dueling Ca2+ sensors in neurotransmitter release. AB - Ca(2+)-triggered neurotransmitter release is characterized by two kinetically distinct components: a fast synchronous phase and a slow asynchronous phase. Yao et al. (2011) now report that double C2 domain (Doc2) proteins function as high affinity Ca(2+) sensors to specifically regulate the asynchronous component of neurotransmitter release. PMID- 22036558 TI - Two routes for remembering the past. AB - Which brain circuits underlie retrieval of distant memories? Goshen et al. (2011) use a powerful optogenetic-based approach to reveal the critical contribution of the hippocampus to remote memory retrieval. In so doing, they provide new evidence toward resolving a long-standing debate in cognitive neuroscience. PMID- 22036559 TI - Drop that pipette: science by design. AB - An unexpected collaboration between a synthetic biology lab at UCSF and a Palo Alto-based design firm is stirring up the way that research is conceived and conducted, by integrating innovation and "design thinking" into the scientific method. PMID- 22036560 TI - The seeds of neurodegeneration: prion-like spreading in ALS. AB - Misfolded proteins accumulating in several neurodegenerative diseases (including Alzheimer, Parkinson, and Huntington diseases) can cause aggregation of their native counterparts through a mechanism similar to the infectious prion protein's induction of a pathogenic conformation onto its cellular isoform. Evidence for such a prion-like mechanism has now spread to the main misfolded proteins, SOD1 and TDP-43, implicated in amyotrophic lateral sclerosis (ALS). The major neurodegenerative diseases may therefore have mechanistic parallels for non-cell autonomous spread of disease within the nervous system. PMID- 22036561 TI - Molecular mechanisms of fear learning and memory. AB - Pavlovian fear conditioning is a particularly useful behavioral paradigm for exploring the molecular mechanisms of learning and memory because a well-defined response to a specific environmental stimulus is produced through associative learning processes. Synaptic plasticity in the lateral nucleus of the amygdala (LA) underlies this form of associative learning. Here, we summarize the molecular mechanisms that contribute to this synaptic plasticity in the context of auditory fear conditioning, the form of fear conditioning best understood at the molecular level. We discuss the neurotransmitter systems and signaling cascades that contribute to three phases of auditory fear conditioning: acquisition, consolidation, and reconsolidation. These studies suggest that multiple intracellular signaling pathways, including those triggered by activation of Hebbian processes and neuromodulatory receptors, interact to produce neural plasticity in the LA and behavioral fear conditioning. Collectively, this body of research illustrates the power of fear conditioning as a model system for characterizing the mechanisms of learning and memory in mammals and potentially for understanding fear-related disorders, such as PTSD and phobias. PMID- 22036562 TI - Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection. AB - The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar capillary network eradicated by viral infection. The dynamics of this p63 expressing stem cell in lung regeneration mirrors our parallel finding that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease. PMID- 22036563 TI - Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization. AB - To identify pathways involved in adult lung regeneration, we employ a unilateral pneumonectomy (PNX) model that promotes regenerative alveolarization in the remaining intact lung. We show that PNX stimulates pulmonary capillary endothelial cells (PCECs) to produce angiocrine growth factors that induce proliferation of epithelial progenitor cells supporting alveologenesis. Endothelial cells trigger expansion of cocultured epithelial cells, forming three dimensional angiospheres reminiscent of alveolar-capillary sacs. After PNX, endothelial-specific inducible genetic ablation of Vegfr2 and Fgfr1 in mice inhibits production of MMP14, impairing alveolarization. MMP14 promotes expansion of epithelial progenitor cells by unmasking cryptic EGF-like ectodomains that activate the EGF receptor (EGFR). Consistent with this, neutralization of MMP14 impairs EGFR-mediated alveolar regeneration, whereas administration of EGF or intravascular transplantation of MMP14(+) PCECs into pneumonectomized Vegfr2/Fgfr1-deficient mice restores alveologenesis and lung inspiratory volume and compliance function. VEGFR2 and FGFR1 activation in PCECs therefore increases MMP14-dependent bioavailability of EGFR ligands to initiate and sustain alveologenesis. PMID- 22036564 TI - The Eph-receptor A7 is a soluble tumor suppressor for follicular lymphoma. AB - Insights into cancer genetics can lead to therapeutic opportunities. By cross referencing chromosomal changes with an unbiased genetic screen we identify the ephrin receptor A7 (EPHA7) as a tumor suppressor in follicular lymphoma (FL). EPHA7 is a target of 6q deletions and inactivated in 72% of FLs. Knockdown of EPHA7 drives lymphoma development in a murine FL model. In analogy to its physiological function in brain development, a soluble splice variant of EPHA7 (EPHA7(TR)) interferes with another Eph-receptor and blocks oncogenic signals in lymphoma cells. Consistent with this drug-like activity, administration of the purified EPHA7(TR) protein produces antitumor effects against xenografted human lymphomas. Further, by fusing EPHA7(TR) to the anti-CD20 antibody (rituximab) we can directly target this tumor suppressor to lymphomas in vivo. Our study attests to the power of combining descriptive tumor genomics with functional screens and reveals EPHA7(TR) as tumor suppressor with immediate therapeutic potential. PMID- 22036565 TI - Master transcription factors determine cell-type-specific responses to TGF-beta signaling. AB - Transforming growth factor beta (TGF-beta) signaling, mediated through the transcription factors Smad2 and Smad3 (Smad2/3), directs different responses in different cell types. Here we report that Smad3 co-occupies the genome with cell type-specific master transcription factors. Thus, Smad3 occupies the genome with Oct4 in embryonic stem cells (ESCs), Myod1 in myotubes, and PU.1 in pro-B cells. We find that these master transcription factors are required for Smad3 occupancy and that TGF-beta signaling largely affects the genes bound by the master transcription factors. Furthermore, we show that induction of Myod1 in nonmuscle cells is sufficient to redirect Smad3 to Myod1 sites. We conclude that cell-type specific master transcription factors determine the genes bound by Smad2/3 and are thus responsible for orchestrating the cell-type-specific effects of TGF-beta signaling. PMID- 22036566 TI - Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration. AB - BMP and Wnt signaling pathways control essential cellular responses through activation of the transcription factors SMAD (BMP) and TCF (Wnt). Here, we show that regeneration of hematopoietic lineages following acute injury depends on the activation of each of these signaling pathways to induce expression of key blood genes. Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent to hematopoietic genes. In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage regulator during differentiation from multipotent hematopoietic progenitor cells to erythroid cells. Furthermore, induction of the myeloid lineage regulator C/EBPalpha in erythroid cells shifts binding of SMAD1 to sites newly occupied by C/EBPalpha, whereas expression of the erythroid regulator GATA1 directs SMAD1 loss on nonerythroid targets. We conclude that the regenerative response mediated by BMP and Wnt signaling pathways is coupled with the lineage master regulators to control the gene programs defining cellular identity. PMID- 22036567 TI - Molecular architecture of the transport channel of the nuclear pore complex. AB - The nuclear pore complex encloses a central channel for nucleocytoplasmic transport, which is thought to consist of three nucleoporins, Nup54, Nup58, and Nup62. However, the structure and composition of the channel are elusive. We determined the crystal structures of the interacting domains between these nucleoporins and pieced together the molecular architecture of the mammalian transport channel. Located in the channel midplane is a flexible Nup54?Nup58 ring that can undergo large rearrangements yielding diameter changes from ~20 to ~40 nm. Nup62?Nup54 triple helices project alternately up and down from either side of the midplane ring and form nucleoplasmic and cytoplasmic entries. The channel consists of as many as 224 copies of the three nucleoporins, amounting to a molar mass of 12.3 MDa and contributing 256 phenylalanine-glycine repeat regions. We propose that the occupancy of these repeat regions with transport receptors modulates ring diameter and transport activity. PMID- 22036568 TI - Altered modes of stem cell division drive adaptive intestinal growth. AB - Throughout life, adult organs continually adapt to variable environmental factors. Adaptive mechanisms must fundamentally differ from homeostatic maintenance, but little is known about how physiological factors elicit tissue remodeling. Here, we show that specialized stem cell responses underlie the adaptive resizing of a mature organ. In the adult Drosophila midgut, intestinal stem cells interpret a nutrient cue to "break homeostasis" and drive growth when food is abundant. Activated in part by niche production of insulin, stem cells direct a growth program through two altered modes of behavior: accelerated division rates and predominance of symmetric division fates. Together, these altered modes produce a net increase in total intestinal cells, which is reversed upon withdrawal of food. Thus, tissue renewal programs are not committed to maintain cellular equilibrium; stem cells can remodel organs in response to physiological triggers. PMID- 22036569 TI - Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent beta amyloid generation. AB - Assemblies of beta-amyloid (Abeta) peptides are pathological mediators of Alzheimer's Disease (AD) and are produced by the sequential cleavages of amyloid precursor protein (APP) by beta-secretase (BACE1) and gamma-secretase. The generation of Abeta is coupled to neuronal activity, but the molecular basis is unknown. Here, we report that the immediate early gene Arc is required for activity-dependent generation of Abeta. Arc is a postsynaptic protein that recruits endophilin2/3 and dynamin to early/recycling endosomes that traffic AMPA receptors to reduce synaptic strength in both hebbian and non-hebbian forms of plasticity. The Arc-endosome also traffics APP and BACE1, and Arc physically associates with presenilin1 (PS1) to regulate gamma-secretase trafficking and confer activity dependence. Genetic deletion of Arc reduces Abeta load in a transgenic mouse model of AD. In concert with the finding that patients with AD can express anomalously high levels of Arc, we hypothesize that Arc participates in the pathogenesis of AD. PMID- 22036570 TI - Motor neuron position and topographic order imposed by beta- and gamma-catenin activities. AB - Neurons typically settle at positions that match the location of their synaptic targets, creating topographic maps. In the spinal cord, the organization of motor neurons into discrete clusters is linked to the location of their muscle targets, establishing a topographic map of punctate design. To define the significance of motor pool organization for neuromuscular map formation, we assessed the role of cadherin-catenin signaling in motor neuron positioning and limb muscle innervation. We find that joint inactivation of beta- and gamma-catenin scrambles motor neuron settling position in the spinal cord but fails to erode the predictive link between motor neuron transcriptional identity and muscle target. Inactivation of N-cadherin perturbs pool positioning in similar ways, albeit with reduced penetrance. These findings reveal that cadherin-catenin signaling directs motor pool patterning and imposes topographic order on an underlying identity based neural map. PMID- 22036571 TI - Patterns of spinal sensory-motor connectivity prescribed by a dorsoventral positional template. AB - Sensory-motor circuits in the spinal cord are constructed with a fine specificity that coordinates motor behavior, but the mechanisms that direct sensory connections with their motor neuron partners remain unclear. The dorsoventral settling position of motor pools in the spinal cord is known to match the distal to-proximal position of their muscle targets in the limb, but the significance of invariant motor neuron positioning is unknown. An analysis of sensory-motor connectivity patterns in FoxP1 mutant mice, where motor neuron position has been scrambled, shows that the final pattern of sensory-motor connections is initiated by the projection of sensory axons to discrete dorsoventral domains of the spinal cord without regard for motor neuron subtype or, indeed, the presence of motor neurons. By implication, the clustering and dorsoventral settling position of motor neuron pools serve as a determinant of the pattern of sensory input specificity and thus motor coordination. PMID- 22036574 TI - SnapShot: Autism and the synapse. PMID- 22036572 TI - Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release. AB - Synaptic transmission involves a fast synchronous phase and a slower asynchronous phase of neurotransmitter release that are regulated by distinct Ca(2+) sensors. Though the Ca(2+) sensor for rapid exocytosis, synaptotagmin I, has been studied in depth, the sensor for asynchronous release remains unknown. In a screen for neuronal Ca(2+) sensors that respond to changes in [Ca(2+)] with markedly slower kinetics than synaptotagmin I, we observed that Doc2--another Ca(2+), SNARE, and lipid-binding protein--operates on timescales consistent with asynchronous release. Moreover, up- and downregulation of Doc2 expression levels in hippocampal neurons increased or decreased, respectively, the slow phase of synaptic transmission. Synchronous release, when triggered by single action potentials, was unaffected by manipulation of Doc2 but was enhanced during repetitive stimulation in Doc2 knockdown neurons, potentially due to greater vesicle availability. In summary, we propose that Doc2 is a Ca(2+) sensor that is kinetically tuned to regulate asynchronous neurotransmitter release. PMID- 22036573 TI - A protein complex network of Drosophila melanogaster. AB - Determining the composition of protein complexes is an essential step toward understanding the cell as an integrated system. Using coaffinity purification coupled to mass spectrometry analysis, we examined protein associations involving nearly 5,000 individual, FLAG-HA epitope-tagged Drosophila proteins. Stringent analysis of these data, based on a statistical framework designed to define individual protein-protein interactions, led to the generation of a Drosophila protein interaction map (DPiM) encompassing 556 protein complexes. The high quality of the DPiM and its usefulness as a paradigm for metazoan proteomes are apparent from the recovery of many known complexes, significant enrichment for shared functional attributes, and validation in human cells. The DPiM defines potential novel members for several important protein complexes and assigns functional links to 586 protein-coding genes lacking previous experimental annotation. The DPiM represents, to our knowledge, the largest metazoan protein complex map and provides a valuable resource for analysis of protein complex evolution. PMID- 22036575 TI - Prefrontal activation patterns of automatic and regulated approach-avoidance reactions - a functional near-infrared spectroscopy (fNIRS) study. AB - INTRODUCTION: The present pilot study investigated cortical processes during automatic and regulated approach-avoidance reactions for the first time. METHODS 1: In 15 healthy volunteers, prefrontal activity was measured with functional near-infrared spectroscopy (fNIRS) during performance of a joystick version of the Approach-Avoidance Task (AAT). In experiment 1, participants approached (pulled towards their body) and avoided (pushed away from their body) positive and negative pictures. RESULTS 1: Incompatible, regulated reactions (avoid positive, approach negative) compared to compatible, automatic reactions (approach positive, avoid negative) caused stronger activation in terms of a decrease of deoxygenated haemoglobin (HHb) in right dorsolateral prefrontal cortex (DLPFC) (i.e., in one of the main instances for behavioural control in humans). METHODS 2: In the context of pathologically enhanced approach tendencies in addiction disorders and of planned future studies, we presented alcohol and non-alcohol pictures in experiment 2. RESULTS 2: Here, left anterior lateral orbitofrontal cortex as part of the general reward system processing secondary rewards showed stronger activation in terms of increased oxygenated haemoglobin (O(2)Hb) during approaching compared to avoiding alcohol pictures. This difference was positively correlated with participants' expectation about beneficial effects of alcohol in terms of emotional regulation. DISCUSSION: Despite some limitations due to the pilot character of the study, our results suggest that further combinations of the AAT and functional imaging methods will reveal detailed insight into neuronal mechanisms constituting approach-avoidance as basic behavioural principles and into specifically altered sub-processes in alcohol dependence. PMID- 22036576 TI - Dermatologist response rates to a mailed questionnaire: a randomized trial of monetary incentives. PMID- 22036577 TI - Where is the international variation in the protection of the public? Commentary on Cutcliffe and Forster (2010). PMID- 22036578 TI - Family caregivers' decision process to institutionalize persons with Parkinson's disease: a grounded theory study. AB - BACKGROUND: Parkinson's disease is a degenerative neurological disorder affecting millions. Treatment priorities focus on delaying its progression and resulting disability, and helping individuals continue to live at home as long as possible. This often requires long-term assistance by family caregivers. AIMS: The purpose of the study was to understand (1) family caregivers' experiences in caring for a relative with Parkinson's disease, and (2) factors that influenced the decision to place the relative in a long-term care facility. PARTICIPANTS: Twenty semi structured interviews were conducted with adult family members (17 female, 3 male) acting as full-time primary caregivers for a relative with Parkinson's disease. METHOD: Grounded theory was used to explore the process of healthcare decision-making and to illustrate the experiences of caring for persons with Parkinson's disease. The interview questions centered on family caregiving experiences and on how these caregivers made long-term care decisions on behalf of their loved ones. Data were coded and analyzed using dimensional analysis. FINDINGS: The caregiving model developed from the data illustrated that heightened caregiver strain-a risk factor for institutionalization-results from increased caregiving load and increased illness severity over time. Safety concerns, falls with severe injury, managing changes in health, and depleted support also influenced the decision to institutionalize the relative with Parkinson's disease. CONCLUSIONS: Implications from this research suggest the need for enhanced communication between providers and caregivers, formalized caregiver assessments, improved care coordination and family-centered interventions to avoid premature institutionalization. PMID- 22036579 TI - Synaptotagmin 1 causes phosphatidyl inositol lipid-dependent actin remodeling in cultured non-neuronal and neuronal cells. AB - Here we demonstrate that a dramatic actin polymerizing activity caused by ectopic expression of the synaptic vesicle protein synaptotagmin 1 that results in extensive filopodia formation is due to the presence of a lysine rich sequence motif immediately at the cytoplasmic side of the transmembrane domain of the protein. This polybasic sequence interacts with anionic phospholipids in vitro, and, consequently, the actin remodeling caused by this sequence is interfered with by expression of a phosphatidyl inositol (4,5)-bisphosphate (PIP2)-targeted phosphatase, suggesting that it intervenes with the function of PIP2-binding actin control proteins. The activity drastically alters the behavior of a range of cultured cells including the neuroblastoma cell line SH-SY5Y and primary cortical mouse neurons, and, since the sequence is conserved also in synaptotagmin 2, it may reflect an important fine-tuning role for these two proteins during synaptic vesicle fusion and neurotransmitter release. PMID- 22036580 TI - The effect of lumbosacral manipulation on corticospinal and spinal reflex excitability on asymptomatic participants. AB - OBJECTIVE: The aim of the study was to examine the effects of a high-velocity, low-amplitude (HVLA) manipulation to the lumbosacral joint on corticospinal excitability, as measured by motor evoked potentials (MEPs) using transcranial magnetic stimulation, and spinal reflex excitability, as measured by the Hoffman reflex (H-reflex). METHODS: In a randomized, controlled, crossover design, 14 asymptomatic volunteers (mean age, 23 +/- 5.4 years; 10 men; 4 women) were measured for MEPs and H-reflexes immediately before and after a randomly allocated intervention. The interventions consisted of HVLA applied bilaterally to the lumbosacral joint and a control intervention. Participants returned a week later, and the same procedures were performed using the other intervention. Data for H-reflex and MEP amplitudes were normalized to the M-wave maximum amplitude and analyzed using 2-way analysis of variance with repeated measures. RESULTS: A significant interaction of treatment by time was found for MEP (F(1,13) = 4.87, P = .04), and post hoc analyses showed that the MEP/M-wave maximum ratio decreased significantly in the HVLA treatment (P = .02; effect size, 0.68). For H-reflex, there was a significant effect of time (F(1,13) = 8.186, P = .01) and treatment and time interaction (F(1,13) = 9.05, P = .01), with post hoc analyses showing that H-reflexes were significantly reduced after the HVLA manipulation (P = .004; effect size, 0.94). There were no significant changes in MEP latency or silent period duration. CONCLUSION: An HVLA manipulation applied to the lumbosacral joint produced a significant decrease in corticospinal and spinal reflex excitability, and no significant change occurred after the control intervention. The changes in H-reflexes were larger than those in MEPs, suggesting a greater degree of inhibition at the level of the spinal cord. PMID- 22036581 TI - Evaluation of biologic meshes in a porcine model of ventral incisional hernia repair. PMID- 22036583 TI - Antivenom use for copperhead envenomations. PMID- 22036587 TI - Alphabetic letter identification: effects of perceivability, similarity, and bias. AB - The legibility of the letters in the Latin alphabet has been measured numerous times since the beginning of experimental psychology. To identify the theoretical mechanisms attributed to letter identification, we report a comprehensive review of literature, spanning more than a century. This review revealed that identification accuracy has frequently been attributed to a subset of three common sources: perceivability, bias, and similarity. However, simultaneous estimates of these values have rarely (if ever) been performed. We present the results of two new experiments which allow for the simultaneous estimation of these factors, and examine how the shape of a visual mask impacts each of them, as inferred through a new statistical model. Results showed that the shape and identity of the mask impacted the inferred perceivability, bias, and similarity space of a letter set, but that there were aspects of similarity that were robust to the choice of mask. The results illustrate how the psychological concepts of perceivability, bias, and similarity can be estimated simultaneously, and how each make powerful contributions to visual letter identification. PMID- 22036586 TI - A unified model of mammalian BCL-2 protein family interactions at the mitochondria. AB - During apoptosis, the BCL-2 protein family controls mitochondrial outer membrane permeabilization (MOMP), but the dynamics of this regulation remain controversial. We employed chimeric proteins composed of exogenous BH3 domains inserted into a tBID backbone that can activate the proapoptotic effectors BAX and BAK to permeabilize membranes without being universally sequestered by all antiapoptotic BCL-2 proteins. We thus identified two "modes" whereby prosurvival BCL-2 proteins can block MOMP, by sequestering direct-activator BH3-only proteins ("MODE 1") or by binding active BAX and BAK ("MODE 2"). Notably, we found that MODE 1 sequestration is less efficient and more easily derepressed to promote MOMP than MODE 2. Further, MODE 2 sequestration prevents mitochondrial fusion. We provide a unified model of BCL-2 family function that helps to explain otherwise paradoxical observations relating to MOMP, apoptosis, and mitochondrial dynamics. PMID- 22036588 TI - Fearful expressions enhance recognition memory: electrophysiological evidence. AB - Facial expressions play a key role in affective and social behavior. However, the temporal dynamics of the brain responses to emotional faces remain still unclear, in particular an open question is at what stage of face processing expressions might influence encoding and recognition memory. To try and answer this question we recorded the event-related potentials (ERPs) elicited in an old/new recognition task. A novel aspect of the present design was that whereas faces were presented during the study phase with either a happy, fearful or neutral expression, they were always neutral during the memory retrieval task. The ERP results showed three main findings: An enhanced early fronto-central positivity for faces encoded as fearful, both during the study and the retrieval phase. During encoding subsequent memory (Dm effect) was influenced by emotion. At retrieval the early components P100 and N170 were modulated by the emotional expression of the face at the encoding phase. Finally, the later ERP components related to recognition memory were modulated by the previously encoded facial expressions. Overall, these results suggest that face recognition is modulated by top-down influences from brain areas associated with emotional memory, enhancing encoding and retrieval in particular for fearful emotional expressions. PMID- 22036589 TI - Finite element analysis of bonded model Class I 'restorations' after shrinkage. AB - OBJECTIVES: The C-Factor has been used widely to rationalize the changes in shrinkage stress occurring at the tooth/resin-composite interfaces. Experimentally, such stresses have been measured in a uniaxial direction between opposed parallel walls. The situation of adjoining cavity walls has been neglected. The aim was to investigate the hypothesis that: within stylized model rectangular cavities of constant volume and wall thickness, the interfacial shrinkage-stress at the adjoining cavity walls increases steadily as the C-Factor increases. METHODS: Eight 3D-FEM restored Class I 'rectangular cavity' models were created by MSC.PATRAN/MSC.Marc, r2-2005 and subjected to 1% of shrinkage, while maintaining constant both the volume (20 mm(3)) and the wall thickness (2 mm), but varying the C-Factor (1.9-13.5). An adhesive contact between the composite and the teeth was incorporated. Polymerization shrinkage was simulated by analogy with thermal contraction. Principal stresses and strains were calculated. Peak values of maximum principal (MP) and maximum shear (MS) stresses from the different walls were displayed graphically as a function of C-Factor. The stress-peak association with C-Factor was evaluated by the Pearson correlation between the stress peak and the C-Factor. RESULTS: The hypothesis was rejected: there was no clear increase of stress-peaks with C-Factor. The stress peaks particularly expressed as MP and MS varied only slightly with increasing C Factor. Lower stress-peaks were present at the pulpal floor in comparison to the stress at the axial walls. In general, MP and MS were similar when the axial wall dimensions were similar. The Pearson coefficient only expressed associations for the maximum principal stress at the ZX wall and the Z axis. SIGNIFICANCE: Increase of the C-Factor did not lead to increase of the calculated stress-peaks in model rectangular Class I cavity walls. PMID- 22036590 TI - Repair of silorane composite--using the same substrate or a methacrylate-based composite? AB - OBJECTIVE: The study aimed to analyze the shear bond strength of aged silorane composite repaired with the same substrate or a conventional methacrylate-based composite after different mechanical and adhesive surface treatments. METHODS: Silorane composite specimens were aged by thermal cycling (5000 cycles, 5-55 degrees C) and randomly assigned to different surface treatments (each group n=16): diamond bur abrasion, aluminum oxide sandblasting, silica coating, or hydrofluoric acid etching. Then, an adhesive system corresponding to the repair composite or a combination of silane agent and the respective adhesive was applied. Silorane composite or a nanofiller composite were adhered onto the conditioned surfaces. In the control group (n=16), silorane composite was adhered to fresh substrate (incremental build up). After further thermal cycling, shear bond strength was tested and failure modes were assessed. Data were analyzed by ANOVA/post hoc tests, Weibull statistics and Chi(2)-test (p<=0.05). RESULTS: Incremental shear bond strength (control group: 21.0+/-10.5 MPa) was achieved by all groups except those etched with hydrofluoric acid or samples abraded with diamond bur and repaired with the nanofiller composite without silane application. Generally, the application of the silane agent improved repair bond strength of the nanofiller but not of the silorane composite. Cohesive failure was observed more frequently than adhesive failure when the silane agent was applied or when silorane composite was used for repair. SIGNIFICANCE: Silorane composite can be repaired with either the same substrate or a methacrylate-based nanofiller composite but requires mechanical surface treatment and--in case of the methacrylate-based composite--silanization prior to adhesive application. PMID- 22036591 TI - Maternal risk factors for preterm birth: a country-based population analysis. AB - OBJECTIVE: The aim of this study was to identify maternal risk factors for spontaneous preterm birth (PTB) compared to delivery at term, in order to recognize high risk women and to provide a global overview of the Italian situation. STUDY DESIGN: A multicenter, observational and retrospective, cross sectional study was designed. The study population comprised 7634 women recruited in 9 different University Maternity Hospitals in Italy. The main criteria for inclusion were: women having had vaginal preterm or term spontaneous delivery in each participating centre during the study period. The records related to deliveries occurring between April and December 2008. A multivariable logistic regression was employed to identify independent predictors of spontaneous preterm birth. Odds ratios (ORs) and 95% confidence intervals (95% CI) were reported with two-tailed probability (p) values. Statistical calculations were carried out using SAS version 9.1. A two-tailed p-value of 0.05 was used to define statistical significant results. RESULTS: A significant increased risk of PTB was found in women with BMI>25 (OR=1.662; 95% CI=1.033-2.676; p-value=0.0365) and in women employed in heavy work (OR=1.947; 95% CI=1.182-3.207; p-value=0.0089). Moreover there was a significant association between PTB and previous reproductive history. In fact a history of previous abortion (OR=1.954; 95% CI=1.162-3.285; p-value=0.0116) or previous cesarean section (OR=2.904; 95% CI=1.066-7.910; p-value=0.0371) was positively correlated to the increased risk of PTB and an important statistically significant association was calculated between PTB and previous pre-term delivery (OR=3.412; 95% CI=1.342-8.676; p value=0.0099). All the other covariates examined as potential risk factors for PTB were not found to be statistically significantly related (p-value>0.05). CONCLUSIONS: The present study, applied to a substantial sample of Italian population, demonstrates that there are peculiar risk factors for spontaneous PTB in the Italian population examined. It shows an association between preterm delivery and certain maternal factors as: BMI, employment, previous abortions, previous PTBs and previous cesarean section. PMID- 22036592 TI - Utility of chemical shift and diffusion-weighted imaging in characterization of hyperattenuating adrenal lesions at 3.0T. AB - OBJECTIVE: The purpose of our study was to evaluate the value of chemical shift imaging (CSI) and diffusion weighted imaging (DWI) at 3.0 T MRI in adrenal hyperattenuating lesions. METHODS: Fifty-one hyperattenuating adrenal lesions in 40 patients were evaluated. Signal intensity index (SII), adrenal to spleen ratio (ASR) and apparent diffusion coefficient (ADC) were used as quantitative analysis parameters. RESULTS: The mean SII, ASR and ADC values were: benign pheochromocytomas (n=22), 7.04%; 0.96, 1.15*10(-3) mm(2)/s; lipid-poor adenomas (n=18), 33.77%, 0.71, 1.07*10(-3) mm(2)/s; malignant tumors (n=7), 11.24%; 1.00; 0.92*10(-3) mm(2)/s. There were significant differences between the lipid-poor adenomas and nonadenomas for SII and ASR, and there were significant differences between the benign and the malignant tumor ADC values. The optimal diagnostic threshold point of SII and ASR for lipid-poor adenomas was 11.96%, 0.83, the sensitivity and specificity were 88.9%, 97.5% and 97%, 83.3%. The optimal diagnostic threshold point of ADC value for benign lesions and malignant tumors was 1.04*10(-3) mm(2)/s, the sensitivity and specificity were 61.4% and 85.7%. CONCLUSION: Quantitative analysis of chemical shift MRI and DWI can help to characterize the hyperattenuating adrenal lesions, especially in differentiatiation between the lipid-poor adenomas, the benign pheochromocytomas, and the malignant tumors. PMID- 22036593 TI - [Treating COPD in chronic patients in a primary-care setting]. AB - The aging of the populations in Western countries entails an increase in chronic diseases, which becomes evident with the triad of age, comorbidities and polymedication. chronic obstructive pulmonary disease represents one of the most important causes of morbidity and mortality, with a prevalence in Spain of 10.2% in the population aged 40 to 80. In recent years, it has come to be defined not only as an obstructive pulmonary disease, but also as a systemic disease. Some aspects stand out in its management: smoking, the main risk factor, even though avoidable, is an important health problem; very important levels of underdiagnosis and little diagnostic accuracy, with inadequate use of spirometry; chronic patient profile; exacerbations that affect survival and cause repeated hospitalizations; mobilization of numerous health-care resources; need to propose integral care (health-care education, rehabilitation, promotion of self-care and patient involvement in decision-making). PMID- 22036594 TI - HPLC-MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib and nilotinib in human peripheral blood mononuclear cell (PBMC). AB - A new method using high performance liquid chromatography coupled with electrospray mass spectrometry is described for the quantification of PBMC concentration of tyrosine kinase inhibitors imatinib, dasatinib and nilotinib. A simple PBMC isolation and extraction procedure were applied on 10-14 mL of blood aliquots. Chromatographic separation of drugs and Internal Standard (quinoxaline) was achieved with a gradient (acetonitrile and water+formic acid 0.05%) on a C18 reverse phase analytical column with 25 min of analytical run, at flow rate of 0.25 mL/min. Mean intra- and inter-day precision for all compounds were 8.76 and 12.20%; mean accuracy was -3.86%; extraction recovery ranged within 79 and 91%. Calibration curves ranged from 50.0 to 0.25 ng. The limit of quantification was set at 0.25 ng for all the analyzed drugs. This novel developed methodology allows a specific, sensitive and reliable simultaneous intracellular determination of the three tyrosine kinase inhibitors imatinib, dasatinib and nilotinib in a single chromatographic run, useful for drugs estimation in PBMC of patients affected by chronic myeloid leukemia. PMID- 22036595 TI - Analysis of clinical samples for early detection of classical swine fever during infection with low, moderate, and highly virulent strains in relation to the onset of clinical signs. AB - Classical swine fever (CSF) is a transboundary viral disease affecting swine. The clinical course of disease and the best diagnostic samples for early detection were examined using low, moderate, and highly virulent strains of CSFV inoculated into 8-12 week old domestic pigs. Clinical signs were monitored and recorded. Nasal swabs, tonsil scrapings, blood and tonsils were tested using virus isolation, immunohistochemistry, and real-time reverse transcriptase PCR (rRT PCR).Severe clinical signs appear 3 days post infection (dpi) with the highly virulent strain, correlating with positive tonsil scrapings, tonsil and blood by virus isolation and rRT-PCR (83-100%), whereas nasal swabs become comparable by 5dpi (89-100%). The moderate strain caused less severe clinical signs between 5 and 7dpi, with tonsil scrapings, tonsil and blood positive by 7dpi (83-100%), and nasal swabs were comparable at 10dpi (67-90%). The low virulent strain showed mild clinical signs at 7dpi, with blood, tonsil and tonsil scrapings positive by virus isolation and rRT-PCR. Except for one sample at 10dpi, nasal swabs remained negative throughout the course of infection. This study indicates that irrespective of virulence, whole blood and tonsil scrapings are the sample of choice for early detection of CSFV in live pigs. PMID- 22036596 TI - Efficient generation and rapid isolation via stoplight recombination of Herpes simplex viruses expressing model antigenic and immunological epitopes. AB - Generation and isolation of recombinant herpesviruses by traditional homologous recombination methods can be a tedious, time-consuming process. Therefore, a novel stoplight recombination selection method was developed that facilitated rapid identification and purification of recombinant viruses expressing fusions of immunological epitopes with EGFP. This "traffic-light" approach provided a visual indication of the presence and purity of recombinant HSV-1 isolates by producing three identifying signals: (1) red fluorescence indicates non recombinant viruses that should be avoided; (2) yellow fluorescence indicates cells co-infected with non-recombinant and recombinant viruses that are chosen with caution; (3) green fluorescence indicates pure recombinant isolates and to proceed with preparation of viral stocks. Adaptability of this system was demonstrated by creating three recombinant viruses that expressed model immunological epitopes. Diagnostic PCR established that the fluorescent stoplight indicators were effective at differentiating between the presence of background virus contamination and pure recombinant viruses specifying immunological epitopes. This enabled isolation of pure recombinant viral stocks that exhibited wildtype-like viral replication and cell-to-cell spread following three rounds of plaque purification. Expression of specific immunological epitopes was confirmed by western analysis, and the utility of these viruses for examining host immune responses to HSV-1 was determined by a functional T cell assay. PMID- 22036597 TI - Mutations in familial nocturnal frontal lobe epilepsy might be associated with distinct neurological phenotypes. AB - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare familial seizure disorder caused by mutations in at least two different subunit genes of the neuronal nicotinic acetylcholine receptor (nAChR), CHRNA4 and CHRNB2. ADNFLE was initially described as a "pure" seizure disorder with a mostly benign course. We have analysed the clinical features of 19 ADNFLE families from 12 countries with a total of 150 patients and grouped them with respect to their nAChR mutations. These data suggest that certain nAChR mutations might be associated with an increased risk for major neurological symptoms such as mental retardation, schizophrenia-like symptoms or marked cognitive deficits, but the risk for these disorders seems to be low for most other ADNFLE mutations. The functional data confirm that the mutations differ from each other with respect to the size of their gain-of function effects and other biopharmacological characteristics although these functional changes are not predictive for the severity of the clinical phenotype. PMID- 22036598 TI - Age and gender differences in linkages of sleep with subsequent mortality and health among very old Chinese. AB - BACKGROUND: Studies suggest that sleep quality and duration are significantly associated with mortality risk and health conditions, yet such studies are seldom conducted among very old adults. The objective of this study was to examine associations between self-reported sleep quality/duration and subsequent mortality/health among very old adults in China. A second objective determines whether these associations vary by age and gender. METHODS: This study used data of the 2005 and 2008 waves from a large, representative survey with a total of 12,671 individuals in 22 provinces in mainland China, in which 3158 respondents were aged 90-99 and 2293 were centenarians. Two self-reported questions about sleep quality and duration were examined while adjusting for numerous socio demographic, family/social support, health practices, and baseline health factors. RESULTS: Hazard regressions showed that, when demographic factors are controlled for, Chinese elders who report poor and fair quality of sleep have 26% and 10% higher risk of death over the next three years compared to those with good sleep quality; those who sleep either 6h or less or 10h or more per day have an 18-22% higher mortality risk as compared to those who sleep 8h per day. The increased mortality risks of poorer sleep and too short or too long sleep duration are larger in men than in women and more robust in the oldest-old than in young elders. Logistic regressions show that poor sleep and daily sleep durations of 5h or less or 10h or more are also associated with worse health three years later. CONCLUSIONS: Poorer sleep quality and too short or too long sleep duration are associated with higher subsequent mortality risk and lower odds of being in a healthy state among very old Chinese. PMID- 22036599 TI - Lacrimal surgery in patients with obstructive sleep apnea. PMID- 22036600 TI - Familial aggregation of narcolepsy. AB - OBJECTIVES: To determine the familial aggregation of narcolepsy from perspectives of clinical symptomatology, polysomnographic data, and human leukocyte antigen (HLA) typing. METHODS: This was a Family study at the University-affiliated hospital. The participants were narcolepsy probands and their first degree relatives, and, also, age and sex matched unrelated healthy controls. Interventions were not applicable. MEASUREMENTS AND RESULTS: All study subjects underwent structured interviews, overnight polysomnography followed by a multiple sleep latency test (MSLT), and HLA typing. Altogether, 33 probands and 81 first degree relatives (response rate 65%) were recruited. Among the relatives, 12.3% were diagnosed with narcolepsy and 39.5% had narcolepsy spectrum as defined by unexplained abnormal MSLT (shortened MSL and SOREMP) results. The relative risk of narcolepsy in first degree relatives was 361.8. Familial aggregation of narcolepsy symptoms, excessive daytime sleepiness, HLA status, abnormal MSLT, and nocturnal polysomnographic findings were observed. CONCLUSIONS: The familial risk of narcolepsy among first degree relatives is much higher than previously reported. There exists a spectrum of narcolepsy features among relatives, ranging from full clinical tetrads to asymptomatic abnormal MSLT findings. PMID- 22036601 TI - Sleep duration and emerging cardiometabolic risk markers in adolescents. The AFINOS study. AB - OBJECTIVE: To examine the associations between sleep duration and emerging inflammatory and endothelial function risk factors in adolescents. METHODS: This study included a total of 183 (88 girls) adolescents, aged 13-17 years, without diagnosed sleep-related disorders. White blood cell counts, C-reactive protein (CRP), complement factors 3 and 4, interleukin-6, adiponectin, leptin, inter cellular adhesion molecule 1, vascular cell adhesion molecule-1, E-selectin, l selectin, and plasminogen activator inhibitor-1 were measured. Sleep duration and sleep-related disorders were obtained by self-report and moderate-to-vigorous physical activity (MVPA) was objectively measured by accelerometer. Body mass index (BMI) was calculated from measured height and weight. RESULTS: A significant inverse association between sleep duration and CRP (beta=-0.17, P=0.024) existed only after controlling for sex, age, and pubertal status. The results did not change when MVPA was included into the model. However, the association of sleep duration with CRP was slightly attenuated when BMI was included in the model, though it remained significant (beta=-0.15, P=0.044). CONCLUSION: Short sleep duration during adolescence might play an important and independent role in cardiovascular and metabolic diseases through CRP. PMID- 22036602 TI - Hierarchy of insomnia criteria based on daytime consequences. AB - OBJECTIVES: To explore how insomnia symptoms are hierarchically organized in individuals reporting daytime consequences of their sleep disturbances. METHODS: This is a cross-sectional study conducted in the general population of the states of California, New York, and Texas. The sample included 8937 individuals aged 18 years or older representative of the general population. Telephone interviews on sleep habits and disorders were managed with the Sleep-EVAL expert system and using DSM-IV and ICSD classifications. Insomnia symptoms and global sleep dissatisfaction (GSD) had to occur at least three times per week for at least three months. RESULTS: A total of 26.2% of the sample had a GSD. Individuals with GSD reported at least one insomnia symptom in 73.1% of the cases. The presence of GSD in addition to insomnia symptoms considerably increased the proportion of individuals with daytime consequences related to insomnia. In the classification trees performed, GSD arrived as the first predictor for daytime consequences related to insomnia. The second predictor was nonrestorative sleep followed by difficulty resuming sleep and difficulty initiating sleep. CONCLUSIONS: Classification trees are a useful way to hierarchically organize symptoms and to help diagnostic classifications. In this study, GSD was found to be the foremost symptom in identifying individuals with daytime consequences related to insomnia. PMID- 22036603 TI - A new means of assessing the quality of life of patients with obstructive sleep apnea: the MOSAS questionnaire. AB - BACKGROUND: The nightly use of continuous positive airway pressure (CPAP) increases the quality of life of patients affected by obstructive sleep apnea syndrome (OSAS). The aim of this study was to develop and validate a questionnaire to assess the psychological and physical impact of OSAS and adherence to the CPAP device. METHODS: Ninety-six patients underwent a polygraphic examination to establish a diagnosis of OSAS. They attended educational sessions concerning CPAP and completed the Maugeri Obstructive Sleep Apnea Syndrome (MOSAS) questionnaire before the adaptation phase to the device and after six months, when the number of hours of CPAP use was documented. RESULTS: Exploratory and confirmatory factor analysis of MOSAS section A revealed two factors with good internal consistency: "Sleep Apnea Psychological Impact" (alpha=0.77) and "Sleep Apnea Physical Impact" (alpha=0.75). Structural equation modeling confirmed the goodness of fit of the structure to the observed (RMSEA=0.034; GFI=0.95; AGFI=0.92; and CFI=0.96). MOSAS section B, which assesses the "discomfort and nuisance of CPAP," is mono-factorial with good internal consistency (alpha=0.663). The Psychological Impact factor positively correlated with the anxiety (r=0.44) and depression scores (r=0.49) and the physical impact factor positively correlated with daytime sleepiness (r=0.65). The discomfort and nuisance of CPAP negatively correlated with recorded CPAP use after six months (r=-0.52). CONCLUSIONS: The statistical quality of MOSAS is good, and it can be used to assess the psychological and physical impact of OSAS and subjective adherence to a CPAP device. PMID- 22036604 TI - Patterns in pharyngeal airflow associated with sleep-disordered breathing. AB - OBJECTIVE: To establish the feasibility of a noninvasive method to identify pharyngeal airflow characteristics in sleep-disordered breathing. METHODS: Four patients with sleep-disordered breathing who underwent surgery or used positive airway pressure devices and four normal healthy controls were studied. Three dimensional CT imaging and computational fluid dynamics modeling with standard steady-state numerical formulation were used to characterize pharyngeal airflow behavior in normals and pre-and post-treatment in patients. Dynamic flow simulations using an unsteady approach were performed in one patient. RESULTS: The pre-treatment pharyngeal airway below the minimum cross-sectional area obstruction site showed airflow separation. This generated recirculation airflow regions and enhanced turbulence zones where vortices developed. This interaction induced large fluctuations in airflow variables and increased aerodynamic forces acting on the pharyngeal wall. At post-treatment, for the same volumetric flow rate, airflow field instabilities vanished and airflow characteristics improved. Mean maximum airflow velocity during inspiration reduced from 18.3+/-5.7 m/s pre treatment to 6.3+/-4.5 m/s post-treatment (P=0.002), leading to a reduction in maximum wall shear stress from 4.8+/-1.7 Pa pre-treatment to 0.9+/-1.0 Pa post treatment (P=0.01). The airway resistance improved from 4.3+/-1.4 Pa/L/min at pre treatment to 0.7+/-0.7 Pa/L/min at post-treatment (P=0.004). Post-treatment airflow characteristics were not different from normal controls (all P >= 0.39). CONCLUSION: This study demonstrates that pharyngeal airflow variables may be derived from CT imaging and computational fluid dynamics modeling, resulting in high quality visualizations of airflow characteristics of axial velocity, static pressure, and wall shear stress in sleep-disordered breathing. PMID- 22036605 TI - Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy. AB - BACKGROUND: The neuropeptides hypocretin-1 and -2 (hcrt-1 and -2, also known as orexin A and B) are crucially involved in the regulation of sleep/wake states. On the one hand, the sleep-wake disorder narcolepsy can be caused by an hcrt-1 deficiency. On the other, intracerebral administration of hcrt-1 produces an increase in wakefulness at the expense of REM sleep in normal and narcoleptic animals. In humans intranasal administration has been shown to effectively deliver neuropeptides directly to the central nervous system. We hypothesised that the intranasal application of hcrt-1 increases wakefulness and reduces REM sleep in the natural human hcrt-1 deficiency narcolepsy with cataplexy. METHODS: In this double-blind, random-order crossover, placebo-controlled, within-subject design study we administered human recombinant hcrt-1 (435 nmol) intranasally to eight subjects with narcolepsy with cataplexy before night sleep, followed by standard polysomnography. RESULTS: Although intranasal administration of hcrt-1 had no statistically significant effect on nocturnal wakefulness, we found that it reduced REM sleep quantity, particularly during the second half of the recording. Furthermore, intranasal hcrt-1 had a clear REM sleep stabilising effect and led to significantly reduced direct wake to REM transitions. CONCLUSION: In this pilot study we found, first, evidence that the intranasal administration of hcrt-1 has functional effects on sleep in narcolepsy with cataplexy. Our results may encourage the use of the intranasal approach in further studies on hypocretinergic sleep regulation and might also contribute to the future development of a causal treatment for narcolepsy with cataplexy. PMID- 22036606 TI - Evidence for complete epistasis of null mutations in murine Fanconi anemia genes Fanca and Fancg. AB - Fanconi anemia (FA) is a heritable disease characterized by bone marrow failure, congenital abnormalities, and cancer predisposition. The 15 identified FA genes operate in a molecular pathway to preserve genomic integrity. Within this pathway the FA core complex operates as an ubiquitin ligase that activates the complex of FANCD2 and FANCI to coordinate DNA repair. The FA core complex is formed by at least 12 proteins. However, only the FANCL subunit displays ubiquitin ligase activity. FANCA and FANCG are members of the FA core complex for which no other functions have been described than to participate in protein interactions. In this study we generated mice with combined null alleles for Fanca and Fancg to identify extended functions for these genes by characterizing the double mutant mice and cells. Double mutant a(-/-)/g(-/-) mice were born at near Mendelian frequencies without apparent developmental abnormalities. Histological analysis of a(-/-)/g(-/-) mice revealed a Leydig cell hyperplasia and frequent vacuolization of Sertoli cells in testes, while ovaries were depleted from developing follicles and displayed an interstitial cell hyperplasia. These gonadal aberrations were associated with a compromised fertility of a(-/-)/g(-/-) males and females. During the first year of life a(-/-)/g(-/-) did not develop malignancies or bone marrow failure. At the cellular level a(-/-)/g(-/-), Fanca( /-), and Fancg(-/-) cells proved equally compromised in DNA crosslink and homology-directed repair. Overall the phenotype of a(-/-)/g(-/-) double knockout mice and cells appeared highly similar to the phenotype of Fanca or Fancg single knockouts. The lack of an augmented phenotype suggest that null mutations in Fanca or Fancg are fully epistatic, making additional important functions outside of the FA core complex highly unlikely. PMID- 22036608 TI - Harnessing the biosynthetic capacity of marine-derived organisms. PMID- 22036607 TI - RAD18-BRCTx interaction is required for efficient repair of UV-induced DNA damage. AB - BRCA1 carboxyl-terminal (BRCT) motifs are present in a number of proteins involved in DNA repair and/or DNA damage signaling pathways. The BRCT domain containing protein BRCTx has been shown to interact physically with RAD18, an E3 ligase involved in postreplication repair and homologous recombination repair. However, the physiological relevance of the interaction between RAD18 and BRCTx is largely unknown. In this study, we showed that RAD18 interacts with BRCTx in a phosphorylation-dependent manner and that this interaction, mediated via highly conserved serine residues on the RAD18 C terminus, is required for BRCTx accumulation at DNA damage sites. Furthermore, we uncovered critical roles of the RAD18-BRCTx module in UV-induced DNA damage repair but not PCNA mono ubiquitination or homologous recombination. Thus, our results suggest that RAD18 has an additional function in the surveillance of the UV-induced DNA damage response signal. PMID- 22036609 TI - Acne severity grading: determining essential clinical components and features using a Delphi consensus. AB - BACKGROUND: There are multiple global scales for acne severity grading but no singular standard. OBJECTIVE: Our objective was to determine the essential clinical components (content items) and features (property-related items) for an acne global grading scale for use in research and clinical practice using an iterative method, the Delphi process. METHODS: Ten acne experts were invited to participate in a Web-based Delphi survey comprising 3 iterative rounds of questions. RESULTS: In round 1, the experts identified the following clinical components (primary acne lesions, number of lesions, extent, regional involvement, secondary lesions, and patient experiences) and features (clinimetric properties, ease of use, categorization of severity based on photographs or text, and acceptance by all stakeholders). In round 2, consensus for inclusion in the scale was established for primary lesions, number, sites, and extent; as well as clinimetric properties and ease of use. In round 3, consensus for inclusion was further established for categorization and acceptance. Patient experiences were excluded and no consensus was achieved for secondary lesions. LIMITATIONS: The Delphi panel consisted solely of the United States (U.S.)-based acne experts. CONCLUSION: Using an established method for achieving consensus, experts in acne vulgaris concluded that an ideal acne global grading scale would comprise the essential clinical components of primary acne lesions, their quantity, extent, and facial and extrafacial sites of involvement; with features of clinimetric properties, categorization, efficiency, and acceptance. PMID- 22036610 TI - Optimal tattoo removal in a single laser session based on the method of repeated exposures. AB - BACKGROUND: Unwanted tattoos are treated with Q-switched lasers. Despite a series of treatments, efficacy is limited. OBJECTIVE: We compared a single Q-switched laser treatment pass with 4 treatment passes separated by 20 minutes. METHODS: Eighteen tattoos on 12 adults were divided in half and randomized. One half received a single treatment pass (the "conventional" method) with a Q-switched alexandrite laser (5.5 J/cm(2), 755 nm, 100-nanosecond pulse duration, 3-mm spot size), and the other half received 4 treatment passes with an interval of 20 minutes between passes (the "R20" method). Tattoo lightening was compared 3 months later, by blinded evaluation of photographs. Biopsy specimens obtained before and immediately after treatment on both halves were also compared in blinded fashion. RESULTS: Immediate whitening reaction occurred on the first treatment pass, with little or no whitening on subsequent passes. Three months later, treatment with the R20 method was much more effective than conventional single-pass laser treatment (P <.01; all tattoos favored the R20 method). Despite greater epidermal injury with the R20 method, neither method caused adverse events or scarring. Light microscopy showed greater dispersion of tattoo ink with the R20 method. LIMITATIONS: This prospective study involved a small number of subjects. CONCLUSIONS: The R20 method is much more effective than conventional laser tattoo treatment, removing most tattoos in a single treatment session. New laser device technology is not required to practice this method. PMID- 22036611 TI - Quantitative analysis predicts the relative therapeutic efficacy of different forms of CTLA4Ig. AB - Modulating the activities of costimulatory molecules controlling immune responses holds considerable promise for immunotherapy. CTLA4Ig (abatacept), a soluble version of the T cell-expressed membrane receptor CTLA-4, is approved for the treatment of rheumatoid arthritis. Like natural CTLA-4 molecules, CTLA4Ig ligates B7-1 and B7-2 on antigen presenting cells, preventing CD28-mediated costimulation of T cells. However, CTLA4Ig can also prevent ligation of CTLA-4, potentially blocking vital inhibitory signals, thereby augmenting immunity. There have been no quantitative analyses of the likely effects of CTLA4Ig on costimulatory interactions at the immunological synapse. We present a mathematical model, based on rigorous biophysical and expression data, for simulating the effects of abatacept and a mutated derivative, LEA29Y, on the synaptic interactions of CD28 and CTLA-4. The simulations reveal an unexpectedly large window within which CD28, but not CTLA-4, ligation is blocked by CTLA4Ig, perhaps explaining the efficacy of abatacept at the recommended therapeutic dose (10mg/kg) and its relative safety. However, the simulations suggest that the present dosing regimen is close to the maximum theoretically safe dose. The simulations also show that, within the therapeutic window, LEA29Y enhances the interaction of CTLA-4 with the more potent of its two native ligands, B7-1. They also suggest that CTLA-4 ligation by B7-1 could, in principle, be enhanced by further decreasing the off rate of CTLA4Ig for binding to B7-2. Our findings therefore offer molecular explanations for why LEA29Y might prove to be more effective than abatacept in a clinical setting, and suggest ways in which its therapeutic efficacy could be further optimised. PMID- 22036612 TI - DNA methylation signatures of the AIRE promoter in thymic epithelial cells, thymomas and normal tissues. AB - Mutations in the AIRE gene cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), which is associated with autoimmunity towards several peripheral organs. The AIRE protein is almost exclusively expressed in medullary thymic epithelial cells (mTEC) and CpG methylation in the promoter of the AIRE gene has been suggested to control its tissue-specific expression pattern. We found that in human AIRE-positive medullary and AIRE-negative cortical epithelium, the AIRE promoter is hypomethylated, whereas in thymocytes, the promoter had high level of CpG methylation. Likewise, in mouse mTECs the AIRE promoter was uniformly hypomethylated. In the same vein, the AIRE promoter was hypomethylated in AIRE-negative thymic epithelial tumors (thymomas) and in several peripheral tissues. Our data are compatible with the notion that promoter hypomethylation is necessary but not sufficient for tissue-specific regulation of the AIRE gene. In contrast, a positive correlation between AIRE expression and histone H3 lysine 4 trimethylation, an active chromatin mark, was found in the AIRE promoter in human and mouse TECs. PMID- 22036613 TI - Expression profiles of three types of GnRH during sex-change in the protandrous cinnamon clownfish, Amphiprion melanopus: Effects of exogenous GnRHs. AB - Gonadotropin-releasing hormones (GnRHs) play pivotal roles in the control of reproduction and gonadal maturation in teleost fish. Fish have multiple GnRH genes that encode structurally distinct peptides. We identified salmon GnRH (sGnRH), seabream GnRH (sbGnRH), and chicken GnRH-II (cGnRH-II) by cDNA cloning in cinnamon clownfish (Amphiprion melanopus) using reverse transcription-PCR (RT PCR) and rapid amplification of cDNA ends-PCR (RACE-PCR). Gene identity was confirmed by sequence alignment and subsequent phylogenetic analyses. We also investigated GnRH mRNA expression in the gonads by quantitative real time-PCR (Q PCR), and measured plasma estradiol-17beta (E(2)) levels in immature fish following treatment with the three molecular forms of GnRHs. The expression levels of sGnRH, sbGnRH, and cGnRH-II mRNA were higher in mature testes and ovaries, as compared to the levels in gonads at earlier stages of maturity. The levels of the three prepro-GnRH mRNA species and the plasma E(2) levels increased after injection of the three GnRH variants. These findings support the hypothesis that GnRH peptides play important roles in the regulation of the hypothalamic pituitary-gonadal axis and are probably involved in paracrine control of gonadal development and sex change in cinnamon clownfish. PMID- 22036614 TI - Pteridine, not carotenoid, pigments underlie the female-specific orange ornament of striped plateau lizards (Sceloporus virgatus). AB - Indicator models of sexual selection suggest that signal honesty is maintained via costs of ornament expression. Carotenoid-based visual signals are a well studied example, as carotenoids may be environmentally limited and impact signaler health. However, not all bright yellow, orange and red ornaments found in vertebrates are carotenoid-based; pteridine pigments may also produce these colors. We examine the contribution of carotenoid and pteridine pigments to the orange reproductive color of female striped plateau lizards (Sceloporus virgatus). This color ornament reliably indicates female mate quality, yet costs maintaining signal honesty are currently unknown. Dietary carotenoid manipulations did not affect orange color, and orange skin differed from surrounding white skin in drosopterin, not carotenoid, content. Further, orange color positively correlated with drosopterin, not carotenoid, concentration. Drosopterin-based female ornaments avoid the direct trade-offs of using carotenoids for ornament production vs egg production, thus may relax counter selection against color ornament exaggeration in females. Direct experimentation is needed to determine the actual costs of pteridine-based ornaments. Like carotenoids, pteridines influence important biological processes, including immune and antioxidant function; predation and social costs may also be relevant. PMID- 22036615 TI - Impacts of calcium signal transduction on the fermentation production of antitumor ganoderic acids by medicinal mushroom Ganoderma lucidum. AB - Recently signal transduction engineering of secondary metabolism is receiving great interest as a powerful tool towards efficient production of valuable secondary metabolites. This work found that the calcineurin-signal transduction was significant to triterpene biosynthesis by higher fungus (mushroom). Addition of calcium ion (at 10mM) to static liquid cultures of Ganoderma lucidum, a famous traditional medicinal mushroom, was proved as a useful strategy to enhance the production of antitumor ganoderic acids (GAs), which resulted in 3.7-, 2.6-, 4.5 , 3.2- and 3.8-fold improvement of total GAs, individual GA-Mk, -T, -S, and -Me, respectively. Experiments using Ca2+ sensor inhibitors indicated the involvement of calcineurin signal in regulating GAs biosynthesis. Quantitative gene transcription analysis revealed that the expression levels of genes of GAs biosynthesis and Ca2+ sensor were up-regulated with calcium addition while down regulated under the inhibitors addition, suggesting that higher GAs production may be resulted from higher expressions of those genes. Based on the results obtained, a possible model on the effect of external calcium ion on the GAs biosynthesis via calcineurin signal transduction pathway was proposed. PMID- 22036616 TI - Effect of sildenafil citrate (Viagra(r)) on trace element concentration in serum and brain of rats. AB - As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180-200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24h after the last injection. Blood samples were collected and serum was separated and stored at -20 degrees C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P<0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats. PMID- 22036617 TI - Pharmacological relationship between nicotinic and opioid systems in analgesia and corticosterone elevation. AB - AIMS: Although a pharmacological relationship is known to exist between nicotine and morphine, the exact mechanisms are unclear. Here, we investigated crosstalk between the endogenous opioid system and nicotinic acetylcholine receptors (nAChRs), specifically in nicotine-induced analgesia and activation of the hypothalamic-pituitary-adrenal (HPA) axis. MAIN METHODS: Nicotine and morphine were administered subcutaneously to mice and the effects of these drugs on analgesia and serum corticosterone (SCS) levels were evaluated by the tail-pinch method and fluorometric assay, respectively. KEY FINDINGS: Both nicotine and morphine produced analgesia and SCS increase after a single injection. Nicotine induced analgesia was prevented by both mecamylamine (MEC; 1mg/kg) and naloxone (NLX; 1mg/kg), and also by repeated administration of morphine or nicotine. Morphine-induced analgesia was prevented by NLX, but not MEC, and by repeated administration of morphine, but not nicotine. Conversely, the nicotine-induced increase in SCS level was prevented by MEC, but not NLX. Morphine-induced SCS increase was prevented by NLX, but not MEC. Moreover, nicotine-induced analgesia was suppressed by dihydro-beta-erythroidine (DHbetaE; an antagonist for the alpha4beta2 nAChR) or methyllycaconitine (MLA; an antagonist for the alpha7 nAChR). The nicotine-induced increase in SCS level was suppressed by DHbetaE, but not MLA. SIGNIFICANCE: Nicotine-induced analgesia may involve the endogenous opioid system through crosstalk with nicotinic pathways. However, the relationship between these systems does not extend to cooperative actions in nicotine-induced HPA-axis activation. PMID- 22036618 TI - Differential effects of systemic interleukin-1beta on gene expression in brainstem noradrenergic nuclei. AB - AIMS: The cytokine, interleukin-1beta (IL-1beta), is known to produce specific effects on the neuroendocrine system such as suppression of the reproductive axis and stimulation of the stress axis. The mechanism by which IL-1beta produces these differential effects is not clear. Since norepinephrine (NE) is involved in these effects, we hypothesized that IL-1beta acts on brainstem noradrenergic nuclei to affect gene transcription of NE synthesizing enzymes, cytokines and associated transcription factors. MAIN METHODS: Adult female Sprague Dawley rats in proestrus were divided into two groups. Control animals received PBS-BSA and the treatment group received 5 MUg of rat recombinant IL-1beta i.p. at noon. They were sacrificed in groups at 1, 3 and 5 pm (n=6/group) for measurement of tyrosine hydroxylase (TH) mRNA by qPCR or at 3 pm for mRNA analysis by qPCR array. KEY FINDINGS: TH mRNA levels decreased gradually with time in both control and IL-1beta-treated rats in the ventrolateral medulla. In the nucleus of solitary tract, TH mRNA levels were significantly reduced by IL-1beta treatment at 5 pm. In the locus coeruleus, TH mRNA levels increased significantly at 5 pm with IL-1beta treatment compared to controls. In the second set of animals analyzed by qPCR array, there were several fold increases in the expression of certain cytokines, chemokines, and transcription factors in specific noradrenergic nuclei. SIGNIFICANCE: Systemic administration of IL-1beta causes significant changes in the expression of tyrosine hydroxylase and several chemokines in brain stem noradrenergic nuclei, thereby mediating its neuroendocrine effects. PMID- 22036619 TI - Comparison of the antinociceptive effects of ibuprofen arginate and ibuprofen in rat models of inflammatory and neuropathic pain. AB - AIMS: Ibuprofen arginate is a highly soluble salt formed by combining racemic ibuprofen with the amino acid l-arginine. This formulation is absorbed faster, and it is safe and effective in treating many forms of mild to moderate pain. We compared the analgesic effect of ibuprofen arginate and conventional ibuprofen in rat models of pain. MAIN METHODS: Mechanical and cold allodynia were assessed in the chronic constriction injury (CCI) model of neuropathic pain, and mechanical allodynia was also examined in capsaicin-injected rats (a model of central sensitization). Inflammatory hypersensitivity was assessed with the formalin test. Ibuprofen-l-arginine, ibuprofen, l-arginine or saline was administered orally on a daily basis after CCI or capsaicin injection, and the von Frey and cold plate tests were performed on days 1, 3 and 7 after CCI or capsaicin administration. In the formalin-induced inflammatory pain test, the drugs were administered 30 min before formalin injection. KEY FINDINGS: Ibuprofen only exerts an antinociceptive effect in the formalin model whereas ibuprofen-l arginine exerts antinociceptive effects on both mechanical and cold allodynia induced by CCI, mechanical allodynia induced by capsaicin injection, and in phase 2 of the formalin test, exhibiting superior antinociceptive activity to ibuprofen in all these tests. l-Arginine only exerted antinociceptive effects on cold allodynia in CCI. SIGNIFICANCE: These results demonstrate that ibuprofen arginate has stronger antinociceptive effects than ibuprofen in all the models used, suggesting it might improve the therapeutic management of neuropathic and inflammatory pain. PMID- 22036620 TI - Metformin and phenformin block the peripheral antinociception induced by diclofenac and indomethacin on the formalin test. AB - AIMS: Recent evidence has shown that systemic administration of sulfonylureas and biguanides block the diclofenac-induced antinociception, but not the effect produced by indomethacin. However, there are no reports about the peripheral interaction between analgesics and the biguanides metformin and phenformin. Therefore, this work was undertaken to determine whether glibenclamide and glipizide and the biguanides metformin and phenformin have any effect on the peripheral antinociception induced by diclofenac and indomethacin. MAIN METHODS: Diclofenac and indomethacin were administered locally in the formalin-injured rat paw, and the antinociceptive effect was evaluated using the 1% formalin test. To determine whether peripheral antinociception induced by diclofenac or indomethacin was mediated by either the ATP-sensitive K(+) channels or biguanides induced mechanisms, the effect of pretreatment with the appropriates vehicles or glibenclamide, glipizide, metformin and phenformin on the antinociceptive effect induced by local peripheral diclofenac and indomethacin was assessed. KEY FINDINGS: Local peripheral injections of diclofenac (50-200 MUg/paw) and indomethacin (200-800 MUg/paw) produced a dose-dependent antinociception during the second phase of the test. Local pretreatment with glibenclamide, glipizide, metformin and phenformin blocked the diclofenac-induced antinociception. On the other hand, the pretreatment with glibenclamide and glipizide did not prevent the local antinociception produced by indomethacin. Nonetheless, metformin and phenformin reversed the local antinociception induced by indomethacin. SIGNIFICANCE: Data suggest that diclofenac could activate the K(+) channels and biguanides-dependent mechanisms to produce its peripheral antinociceptive effects in the formalin test. Likewise, a biguanides-dependent mechanism could be activated by indomethacin consecutively to generate its peripheral antinociceptive effect. PMID- 22036621 TI - The potential of patients' peripheral blood mononuclear cells to differentiate into dendritic cells after hematopoietic stem cell transplantation. AB - AIMS: Although hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological disorders, there is persistent immunosuppression in both allogeneic and autologous HSCT. Dendritic cells (DCs) play key roles in the immune system. This study investigated whether the DC progenitor cells within patients' peripheral blood after HSCT have the potential to differentiate into DCs. MAIN METHODS: Twenty-eight patients were included in this study, and peripheral blood samples were basically taken before starting the conditioning regimen, on the day of transplantation (day 0), and on days +14, +28, +42, +70 and +170 after transplantation. Immature DCs (iDCs) were induced from adherent mononuclear cells by using recombinant human granulocyte-macrophage colony stimulating factor plus interleukin-4. KEY FINDINGS: The iDCs expressed cell surface antigens such as CD40 and HLA-DR, and they had phagocytotic activity, thus showing the characteristics of iDCs. The induction of iDCs was possible from day +14 after HSCT. However, there were differences between allogeneic and autologous HSCT in the expression of CCR5 in iDCs at day +14 after transplantation. Furthermore, the up-regulation of maturation-related antigens by maturation stimuli was higher after HSCT compared with before HSCT. SIGNIFICANCE: We demonstrated that patients' peripheral blood mononuclear cells have the potential to differentiate into DCs beginning on day +14 after HSCT, although some differences exist between allogeneic and autologous HSCT and between before and after HSCT. PMID- 22036622 TI - Protective effect of heme oxygenase-1 induction against hepatic injury in alcoholic steatotic liver exposed to cold ischemia/reperfusion. AB - AIMS: The purpose of this study was to investigate the cytoprotective role of heme oxygenase-1 (HO-1) induction in hepatic injury in alcoholic steatotic liver exposed to cold ischemia/reperfusion (I/R). MAIN METHODS: Animals were fed an ethanol liquid diet or isocaloric control diet for 5 weeks. Isolated perfused rat livers were preserved in Histidine-Tryptophan-Ketoglutarate at 4 degrees C. After 24 h of storage, livers were subjected to 120 min of reperfusion with Krebs Henseleit bicarbonate buffer at 37 degrees C. Animals were pretreated with cobalt protoporphyrin (CoPP, 5 mg/kg, i.p.) or zinc protoporphyrin (ZnPP, 25 mg/kg, i.p.), HO-1 inducer and antagonist, respectively. KEY FINDINGS: In the model of ischemia/isolated perfusion, endogenous HO-1 was downregulated in the livers fed with ethanol diet (ED I/R). In ED I/R group, portal pressure and lactate dehydrogenase release were significantly increased, while bile output and hyaluronic acid clearance decreased compared to rats fed on control diet (CD I/R). Furthermore, hepatic glutathione content decreased and lipid peroxidation increased in the ED I/R group compared to the CD I/R group. These alterations were attenuated by upregulation of HO-1 with CoPP pretreatment. SIGNIFICANCE: Our results suggest that chronic ethanol consumption aggravates hepatic injury during cold I/R and it is likely due to downregulation of endogenous HO-1. Prior induction of HO-1 expression may provide a new strategy to protect livers against hepatic I/R injury or to increase the donor transplant pool through modulation of marginal alcoholic steatotic livers. PMID- 22036623 TI - Casted-immobilization downregulates glucocorticoid receptor expression in rat slow-twitch soleus muscle. AB - AIMS: Glucocorticoids bind to the glucocorticoid receptor (GR) and increase catabolism of muscle proteins via the ubiquitin-proteasome pathway. Activation of beta(2)-adrenergic receptor (beta(2)-AR) in skeletal muscle has been shown to induce muscle hypertrophy by promoting muscle protein synthesis and/or attenuating protein degradation. The aim of this study was to investigate the correlation between disuse-induced muscle atrophy, and expression of GR and beta(2)-AR. METHODS: Rats were subjected to casted-immobilization (knee and foot arthrodesis), a model for muscle disuse, for 10 days. Fast-twitch (extensor digitorum longus: EDL) and slow-twitch (soleus: SOL) muscles were isolated and subsequently used for analysis. The expression of GR and beta(2)-AR was analyzed by real-time RT-PCR and western blotting. In addition, we analyzed plasma catecholamine and corticosterone concentrations by ELISA. KEY FINDINGS: Casted immobilization-induced muscle atrophy was much greater in the SOL muscle than in the EDL muscle. Casted-immobilization decreased the expression of GR mRNA and protein in the SOL muscle but not in the EDL muscle. Although the expression of beta(2)-AR protein in the cytosol and membrane-rich fractions was not changed by casted-immobilization in either muscle, casted-immobilization decreased the expression of beta(2)-AR mRNA in the SOL muscle. Plasma catecholamine and corticosterone concentrations, however, were largely unaffected by casted immobilization during the experimental period. SIGNIFICANCE: This study provides evidence that casted-immobilization-induced muscle disuse downregulates GR expression in slow-twitch muscle. These results suggest that muscle disuse suppresses glucocorticoid signals, such as muscle protein breakdown and transcription of the beta(2)-AR gene, via downregulation of GR expression in slow twitch muscle. PMID- 22036624 TI - Inhibitory effects of salvianolic acid B on apoptosis of Schwann cells and its mechanism induced by intermittent high glucose. AB - AIMS: To investigate protective effects of Salvianolic acid B (Sal B) on the intermittent high glucose (IHG)-induced oxidative stress, mitochondrial pathway activation and Schwann cell (SC) apoptosis in vitro. MAIN METHODS: SCs were primarily cultured and exposed to the different conditions. Apoptosis was confirmed by the Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and concentration of 8-hydroxy-2-deoxy Guanosine (8-OHdG) was detected by Elisa. Intracellular ROS generation and mitochondrial transmembrane potential (DeltaPsim) were detected by flow cytometry analysis. Quantitative real-time reverse transcriptase PCR was performed to analyze the expression levels of Bax and BcL-2. Western blot was performed to analyze the expression levels of some important transcription factors and proteins. KEY FINDINGS: Treatment with Sal B inhibited the IHG-induced oxidative stress by reducing ROS production and 8-OHdG levels, mitochondrial depolarization and apoptosis in SCs in a dose-dependent manner. Furthermore, treatment with Sal B down-regulated the IHG-induced release of cytochrome c, AIF nuclear translocation and Bax expression, but mitigated the IHG-mediated down-regulation of BcL-2 expression in SCs. In addition, treatment with Sal B attenuated the IHG-induced activation of caspase-9 and caspase-3 and minimized the cleavage of PARP in SCs. SIGNIFICANCE: Our results indicated that IHG induced SC apoptosis in both caspase dependent and caspase-independent pathways by activating the mitochondrial pathway. Sal B inhibited the IHG-induced oxidative stress, activation of the mitochondrial pathway and apoptosis in SCs. PMID- 22036625 TI - NCX1 and NCX3: two new effectors of delayed preconditioning in brain ischemia. AB - Substantial evidence has established that a short sub-lethal brain ischemia applied before a prolonged harmful ischemic episode confers ischemic neuroprotection, a phenomenon named ischemic preconditioning. Na(+)/Ca(2+) exchanger (NCX) isoforms, NCX1, NCX2, and NCX3, are plasmamembrane ionic transporters widely distributed in the brain, where they are involved in the control of Na(+) and Ca(2+) homeostasis and in the progression of stroke damage. The objective of this study was to evaluate the role of these three proteins in the preconditioning-induced neuroprotection. NCX protein expression was evaluated at different time points in the ischemic temporoparietal cortex of rats subjected to ischemia alone, to ischemic preconditioning alone, or to ischemic preconditioning plus ischemia. NCX1 and NCX3 were up-regulated in those brain regions protected by preconditioning treatment. These changes were mediated by p AKT, since the p-AKT inhibition prevented the up-regulation of both isoforms. The relevant role of NCX1 and NCX3 during preconditioning was further confirmed when NCX1 and NCX3 silencing, induced by icv infusion of siRNA, partially reverted the preconditioning-induced neuroprotection. The enhancement of NCX1 and NCX3 expression and activity might represent a reasonable strategy to reduce the infarct extension after stroke. PMID- 22036626 TI - HIV-1 Tat neurotoxicity: a model of acute and chronic exposure, and neuroprotection by gene delivery of antioxidant enzymes. AB - HIV-associated neurocognitive disorder (HAND) is an increasingly common, progressive disease characterized by neuronal loss and progressively deteriorating CNS function. HIV-1 gene products, particularly gp120 and Tat elicit reactive oxygen species (ROS) that lead to oxidant injury and cause neuron apoptosis. Understanding of, and developing therapies for, HAND requires accessible models of the disease. We have devised experimental approaches to studying the acute and chronic effects of Tat on the CNS. We studied acute exposure by injecting recombinant Tat protein into the caudate-putamen (CP). Ongoing Tat expression, which more closely mimics HIV-1 infection of the brain, was studied by delivering Tat-expression over time using an SV40-derived gene delivery vector, SV(Tat). Both acute and chronic Tat exposure induced lipid peroxidation and neuronal apoptosis. Finally, prior administration of recombinant SV40 vectors carrying antioxidant enzymes, copper/zinc superoxide dismutase (SOD1) or glutathione peroxidase (GPx1), protected from Tat-induced apoptosis and oxidative injury. Thus, injection of recombinant HIV-1 Tat and the expression vector, SV(Tat), into the rat CP cause respectively acute or ongoing apoptosis and oxidative stress in neurons and may represent useful animal models for studying the pathogenesis and, potentially, treatment of HIV-1 Tat-related damage. PMID- 22036627 TI - Post-discharge follow-up of hospital-associated infections in paediatric patients with conventional questionnaires and electronic surveillance. AB - BACKGROUND: Viral infections are common causes of hospital-associated infections (HAIs) in paediatric patients, with most of these infections only becoming evident after discharge. AIM: To analyse the benefits and costs of conventional and electronic surveillance methods for conducting HAI follow-ups. METHODS: A comparison was made between response rate, time required per patient and costs to the healthcare system of conventional and electronic surveillance methods (sms, e mail, telephone call). FINDINGS: Altogether 1927 patients participated in the conventional followed up in 2001-2003, of whom 1175 (61%) returned the questionnaire; during the electronic surveillance period in 2005-2007, 2309 patients were followed-up in hospital, and 1940 of them (84%) returned the post discharge information to us. The time needed by HCWs was 33 min per patient in the conventional follow-up and 13 min in the electronic follow-up, the total costs per patient being ?15.07 and ?13.61 respectively. A decrease of 17.1% in annual expenses was achieved with the electronic follow-up. The incidence of HAI was 8.4% in the conventional period and 12.2% in the electronic surveillance period, most cases becoming symptomatic after hospitalization. CONCLUSION: Electronic data collection was a convenient way of implementing a continuous HAI follow-up, achieving both a higher participation rate and lower costs. PMID- 22036628 TI - Pilot study examining the association between ambulatory activity and falls among hospitalized older adults. AB - OBJECTIVE: To examine the ambulatory activity of older patients who had a documented fall during hospitalization for acute illness. DESIGN: A retrospective case-control design was used in a pilot study of patients (n=10; >=65y) who had a documented fall during their hospital stay and matched controls (n=25) who did not fall. SETTING: Acute care medical/surgical unit. PARTICIPANTS: Men and women 65 years and older who wore a step activity monitor while hospitalized. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fall incidents during the hospital stay were documented by the nurse in a standardized patient safety event report in accordance with hospital policy. The number of steps per 24-hour interval, time spent walking, and total number of activity episodes were determined for patients and controls. RESULTS: On average +/- SD, patients who fell took 480.3 +/- 432.2 steps per hospital day, spent 53.8 +/- 36.9 minutes walking, and engaged in 25.8 +/- 16.9 episodes of activity. Mean daily steps, time spent walking, and number of activity episodes for patients who did not fall were 680.1 +/- 876.0, 50.1 +/- 58.6, and 21.6 +/- 23.8, respectively. Logistic regression results indicated no association between the fall outcome and mean daily steps (odds ratio=.95; 95% confidence interval, 0.84-1.06). CONCLUSIONS: Ambulatory activity among patients who fell varied widely. Mean daily steps, time spent walking, and number of episodes of activity were comparable with matched controls who did not fall. Patient falls were more likely to be associated with cognitive and hospital environmental factors than actual amount of walking. PMID- 22036629 TI - Manuscript fabrication, image manipulation and plagiarism. PMID- 22036630 TI - Spatial analysis of human lens aquaporin-0 post-translational modifications by MALDI mass spectrometry tissue profiling. AB - Aquaporin-0 (AQP0), the major integral membrane protein in lens fiber cells, becomes highly modified with increasing age. The functional consequences of these modifications are being revealed, and the next step is to determine how these modifications affect the ocular lens, which is directly related to their abundances and spatial distributions. The aim of this study was to utilize matrix assisted laser desorption ionization (MALDI) direct tissue profiling methods, which produce spatially-resolved protein profiles, to map and quantify AQP0 post translational modifications (PTMs). Direct tissue profiling was performed using frozen, equatorial human lens sections of various ages prepared by conditions optimized for MALDI mass spectrometry profiling of membrane proteins. Modified forms of AQP0 were identified and further investigated using liquid chromatography tandem mass spectrometry (LC-MS/MS). The distributions of unmodified, truncated, and oleoylated forms of AQP0 were examined with a maximum spatial resolution of 500 MUm. Direct tissue profiling of intact human lens sections provided high quality, spatially-resolved, relative quantitative information of AQP0 and its modified forms indicating that 50% of AQP0 is truncated at a fiber cell age of 24 +/- 1 year in all lenses examined. Furthermore, direct tissue profiling also revealed previously unidentified AQP0 modifications including N-terminal acetylation and carbamylation. N-terminal acetylation appears to provide a protective effect against N-terminal truncation. PMID- 22036631 TI - Open-angle glaucoma and the risk of erectile dysfunction: a population-based case control study. AB - PURPOSE: Open-angle glaucoma (OAG) is associated with systemic metabolic and cardiovascular disorders, and both share common risk factors with erectile dysfunction (ED). However, few studies have investigated the association of ED with OAG. This study aimed to estimate the association of ED with prior OAG by using a nationwide, population-based data with a retrospective case-control cohort design in Taiwan. DESIGN: Age-matched case-control study. PARTICIPANTS AND CONTROLS: We identified 4605 patients with ED as the cases and randomly selected 23 025 subjects as the controls (5 controls to 1 case). METHODS: We used conditional logistic regression analysis to estimate the odds ratio and 95% confidence interval of having previously been diagnosed with OAG according to the presence/absence of ED after adjusting for patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and alcohol abuse. MAIN OUTCOME MEASURES: We identified OAG cases not only based on an International Classification of Diseases, Ninth Revision, Clinical Modification code, but also by the prescription of topical antiglaucoma medication. RESULTS: In total, prior OAG was found among 137 subjects (0.5 %); 53 individuals (1.1% of the ED patients) from the cases and 84 individuals (0.4% of patients without ED) from the controls. Conditional logistic regression analysis demonstrated that, after adjusting for potential confounders, patients with ED were more likely to have prior OAG than controls (odds ratio, 2.85; 95% confidence interval, 2.10-4.07). CONCLUSIONS: This study identifies a novel association between ED and prior OAG. PMID- 22036632 TI - Immediate changes in intraocular pressure after laser peripheral iridotomy in primary angle-closure suspects. AB - PURPOSE: To determine the immediate changes in intraocular pressure (IOP) after laser peripheral iridotomy in primary angle-closure suspects. DESIGN: Prospective, randomized controlled trial (split-body design). PARTICIPANTS: Seven hundred thirty-four Chinese people 50 to 70 years of age. METHODS: Primary angle closure suspects underwent iridotomy using a neodymium:yttrium-aluminum-garnet laser in 1 randomly selected eye, with the fellow eye serving as a control. Intraocular pressure was measured using Goldmann applanation tonometry before treatment and 1 hour and 2 weeks after treatment. Total energy used and complications were recorded. Risk factors for IOP rise after laser peripheral iridotomy were investigated. MAIN OUTCOME MEASURES: Intraocular pressure. RESULTS: The proportion of treated eyes with an IOP spike (an elevation of >=8 mmHg more than baseline) at 1 hour and 2 weeks after treatment was 9.8% (95% confidence interval [CI], 7.7-12.0) and 0.82% (95% CI, 0.2-1.5), respectively. Only 4 (0.54%) of 734 eyes (95% CI, 0.01-1.08) had an immediate posttreatment IOP of 30 mmHg or more and needed medical intervention. The average IOP 1 hour after treatment was 17.5+/-4.7 mmHg in the treated eyes, as compared with 15.2+/-2.6 mmHg in controls. At 2 weeks after treatment, these values were 15.6+/-3.4 mmHg in treated eyes and 15.1+/-2.7 mmHg in controls (P<0.001). No significant difference was detected in the baseline IOP of the treated and untreated eyes. Logistic regression showed that the incidence of IOP spike was associated with greater laser energy used and shallower central anterior chamber. CONCLUSIONS: Laser peripheral iridotomy in primary angle-closure suspects resulted in significant IOP rise in 9.8% and 0.82% of cases at 1 hour and 2 weeks, respectively. Eyes in which more laser energy and a higher number of laser pulses were used and those with shallower central anterior chambers were at increased risk for IOP spikes at 1 hour after laser peripheral iridotomy. PMID- 22036633 TI - Improved ocular alignment with adjustable sutures in adults undergoing strabismus surgery. AB - OBJECTIVE: To assess whether outcomes of strabismus surgery are improved by using the adjustable suture technique and to determine which subgroups of strabismus patients benefit most from the adjustable suture technique. DESIGN: A retrospective chart review. PARTICIPANTS: A total of 535 adults who underwent strabismus surgery between 1989 and 2010. METHODS: Success was defined as <=10 prism diopters (PD) for horizontal deviations and <=2 PD for vertical deviations. Differences in the proportion of successful strabismus surgery were analyzed using a chi-square test with an alpha of 0.05. MAIN OUTCOME MEASURES: Ocular alignment in primary position at a 7-day to 12-week follow-up examination. RESULTS: A total of 491 patients met the inclusion criteria (nonadjustable suture, n = 186; adjustable suture, n = 305). The success rates for the nonadjustable and adjustable groups were 61.3% and 74.8%, respectively (chi(2)=9.91, P=0.0016). Adjustable suture use was particularly beneficial for patients undergoing a reoperation for childhood strabismus (success rate: nonadjustable, 42.4%; adjustable, 65.7%; P=0.0268; n = 100). The differences in outcomes were not statistically significant for patients with childhood strabismus undergoing a primary surgery (nonadjustable, 65.0%; adjustable, 81.4%; P=0.1354; n = 90) or with thyroid orbitopathy (nonadjustable, 76.7%; adjustable, 74.1%; P=0.8204; n = 57). CONCLUSIONS: Strabismus surgery using adjustable sutures was associated with improved short-term ocular alignment compared with strabismus surgery without the use of adjustable sutures. Adjustable sutures were most beneficial for patients undergoing reoperations for childhood strabismus. PMID- 22036634 TI - Health-related quality of life of bosutinib (SKI-606) in imatinib-resistant or imatinib-intolerant chronic phase chronic myeloid leukemia. AB - Understanding the impact of second-line tyrosine kinase inhibitor therapy on the health-related quality of life (HRQOL) of imatinib (IM)-resistant and IM intolerant chronic phase chronic myeloid leukemia (CP CML) patients is important given the increased survival that comes with therapy. As part of a bosutinib single-arm phase 2 trial, 200 IM-resistant and 88 IM-intolerant CP CML patients' HRQOL was assessed prior to and throughout treatment with the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu). Little HRQOL impairment was demonstrated at baseline. Over the course of 96 weeks on bosutinib therapy, patients noted statistically significant and/or clinically meaningful improvements on several FACT-Leu scales. PMID- 22036635 TI - BCR-ABL1 kinase facilitates localization of acetylated histones 3 and 4 on DNA double-strand breaks. AB - BCR-ABL1 kinase-positive leukemia cells accumulate high numbers of DNA double strand breaks (DSBs) induced by the reactive oxygen species (ROS) or cytotoxic agents. To repair these lesions and prevent apoptosis BCR-ABL1 kinase stimulates the efficiency of DSB repair in leukemia cells. Histone acetylation-dependent chromatin re-modeling plays a crucial role in this process. Here we report that leukemia cells expressing BCR-ABL1 kinase displayed an enhanced histone acetylase activity (HAT) and reduced histone deacetylase activity (HDAC), which was associated with abundant expression of acetylated histones 3 and 4 (Ac-H3 and Ac H4, respectively). Moreover, Ac-H3 and Ac-H4 readily co-localized with the spontaneous and mitomycin C-induced DSBs in BCR-ABL1-positive leukemia cells suggesting that histone acetylation and chromatin re-modeling is important for efficient repair of numerous DSBs. PMID- 22036636 TI - Effect of ultrasonic excitation on the microtensile bond strength of glass ionomer cements to dentin after different water storage times. AB - The application of ultrasound waves on glass ionomer cement (GIC) surface can accelerate the early setting reaction and improve the mechanical properties of the material, resulting in higher resistance to masticatory forces within a short period of time and thus increasing the clinical longevity of the GIC restoration. In this study, the microtensile bond strength (MUTBS) of two high-viscosity GICs (Fuji IX GP and Ketac Molar Easymix) and one resin-modified GIC (RMGIC-Vitremer) to dentin was tested after ultrasonic excitation and water storage. GIC blocks were built up on coronal dentin either receiving or not receiving a 30-s ultrasound application during the material initial setting. After storage in water for either 24 h or 30 d, beam-shaped specimens with a cross-sectional area of approximately 1.0 mm(2) were cut perpendicular to GIC/dentin interface and tested to failure. At 24 h, the ultrasonically set Ketac Molar had significantly higher (p < 0.05) MUTBS than the cement set conventionally. Chemically set Ketac Molar presented significantly higher MUTBS after the longer water storage (p < 0.05). The RMGIC presented the highest MUTBS regardless of ultrasonic excitation and storage period. In conclusion, ultrasound application to Ketac Molar improved its adhesion to dentin, particularly within the first 24 h after setting. Clinically, it seems that ultrasonic excitation can contribute to prevent retention loss of restoration at early stages of GIC setting reaction. PMID- 22036637 TI - Performance assessment of HIFU lesion detection by harmonic motion imaging for focused ultrasound (HMIFU): a 3-D finite-element-based framework with experimental validation. AB - Harmonic motion imaging for focused ultrasound (HMIFU) is a novel high-intensity focused ultrasound (HIFU) therapy monitoring method with feasibilities demonstrated in vitro, ex vivo and in vivo. Its principle is based on amplitude modulated (AM) - harmonic motion imaging (HMI), an oscillatory radiation force used for imaging the tissue mechanical response during thermal ablation. In this study, a theoretical framework of HMIFU is presented, comprising a customized nonlinear wave propagation model, a finite-element (FE) analysis module and an image-formation model. The objective of this study is to develop such a framework to (1) assess the fundamental performance of HMIFU in detecting HIFU lesions based on the change in tissue apparent elasticity, i.e., the increasing Young's modulus, and the HIFU lesion size with respect to the HIFU exposure time and (2) validate the simulation findings ex vivo. The same HMI and HMIFU parameters as in the experimental studies were used, i.e., 4.5-MHz HIFU frequency and 25 Hz AM frequency. For a lesion-to-background Young's modulus ratio of 3, 6 and 9, the FE and estimated HMI displacement ratios were equal to 1.83, 3.69 and 5.39 and 1.65, 3.19 and 4.59, respectively. In experiments, the HMI displacement followed a similar increasing trend of 1.19, 1.28 and 1.78 at 10-s, 20-s and 30-s HIFU exposure, respectively. In addition, moderate agreement in lesion size growth was found in both simulations (16.2, 73.1 and 334.7 mm(2)) and experiments (26.2, 94.2 and 206.2 mm(2)). Therefore, the feasibility of HMIFU for HIFU lesion detection based on the underlying tissue elasticity changes was verified through the developed theoretical framework, i.e., validation of the fundamental performance of the HMIFU system for lesion detection, localization and quantification, was demonstrated both theoretically and ex vivo. PMID- 22036638 TI - Follow-up of high-intensity focused ultrasound treatment for patients with hepatocellular carcinoma. AB - Nonsurgical therapies have become treatment options for hepatocellular carcinoma (HCC). This study was to evaluate the efficacy and complications of high intensity focused ultrasound (HIFU) treatment for patients with HCC. Between May 2001 and May 2005, 145 patients with HCC were enrolled for treatments using a HIFU tumor therapeutic system. Clinical symptoms, hepatic functions and values of serum alpha-fetoprotein (AFP) were tested before and after HIFU treatment. The changes in computerized tomography (CT) and magnetic resonance imaging (MRI), complications and survival time after HIFU were also obtained for further analysis. Symptoms improved or pain was relieved in 84.8% of the 145 patients and the rate of serum AFP decrease was 71.7%. The size of the target tumor shrank by various degrees. The 2-year survival rate was 80% in patients with stage Ib HCC, 51.4% in stage IIa and 46.5% in stage IIIa. During HIFU treatment, complications included body temperature increase and abnormal cardiac rhythm. After HIFU procedures, there were skin burns of different grades. In conclusion, HIFU is safe and effective for patients with hepatocellular carcinoma; HIFU can improve the survival quality of patients with HCC. PMID- 22036639 TI - Observations of translation and jetting of ultrasound-activated microbubbles in mesenteric microvessels. AB - High-speed photomicrography was used to study the translational dynamics of single microbubbles in microvessels of ex vivo rat mesenteries. The microbubbles were insonated by a single 2 MUs ultrasound pulse with a center frequency of 1 MHz and peak negative pressures spanning the range of 0.8-4 MPa. The microvessel diameters ranged from 10-80 MUm. The high-speed image sequences show evidence of ultrasound-activated microbubble translation away from the nearest vessel wall; no microbubble showed a net translation toward the nearest vessel wall. Microbubble maximum translation displacements exceeded 20 MUm. Microjets with the direction of the jets identifiable were also observed; all microjets appear to have been directed away from the nearest vessel wall. These observations appear to be characteristic of a strong coupling between ultrasound-driven microbubbles and compliant microvessels. Although limited to mesenteric tissues, these observations provide an important step in understanding the physical interactions between microbubbles and microvessels. PMID- 22036640 TI - Validity of preoperative ultrasound-guided aspiration in the revision of hip prosthesis. AB - Preoperative diagnosis of septic loosening hip prosthesis is often challenging. Culture test on joint samples obtained during revision surgery is the diagnostic gold standard while the role of preoperative hip aspiration is still controversial. The aims of this prospective randomized study were to compare the sensitivity, specificity and accuracy of preoperative ultrasound-guided and fluoroscopic-guided aspiration, and to identify associated laboratory parameters or scintigraphy that could help in predicting septic loosing hip prosthesis. Sixty patients affected by persistent pain after hip prosthesis randomly received fluoroscopic-guided or ultrasound-guided hip aspiration before revision surgery. The results of culture tests of joint fluid presurgically and at surgery were compared. In addition, associated blood inflammatory markers and scintigraphy were evaluated. Ultrasound-guided aspiration showed a better sensitivity (69% vs. 27%), specificity (94% vs. 75%) and accuracy (83% vs. 40%) than fluoroscopic guided aspiration. The combination of ultrasound-guided aspiration and C-reactive protein represents the best model to predict septic loosening hip prosthesis preoperatively. PMID- 22036641 TI - Impact of age, anthropometric data and body composition on calcaneal bone characteristics, as measured by quantitative ultrasound (QUS) in an older German population. AB - The impact of fat-free mass (FFM), fat mass (FM), body mass index (BMI), body mass and body height on calcaneal bone characteristics as measured with quantitative ultrasound (QUS) was investigated in 137 women and 85 men aged 62-92 years, considering age, smoking, waist-to-hip ratio (WHR) and physical activity level (PAL). In regression analyses using various models, in women, age was a negative predictor of speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) and smoking was a negative predictor of SOS; positive predictors of SOS, BUA, and SI were BMI, body mass and FFM. In men, smoking was a negative predictor and BMI, body mass and FFM were positive predictors of BUA and SI. In both sexes, PAL, body height, WHR and FM had no effect on QUS parameters. The influence of BMI on calcaneal bone characteristics in elderly people depends on FFM rather than on FM. PMID- 22036642 TI - Robotic and laparoscopic high extended pelvic lymph node dissection during radical cystectomy: technique and outcomes. AB - BACKGROUND: With the increasing use of laparoscopic and robotic radical cystectomy (RC), there are perceived concerns about the adequacy of lymph node dissection (LND). OBJECTIVE: Describe the robotic and laparoscopic technique and the short-term outcomes of high extended pelvic LND (PLND) up to the inferior mesenteric artery (IMA) during RC. DESIGN, SETTING, AND PARTICIPANTS: From January 2007 through September 2009, we performed high extended PLND with proximal extent up to the IMA (n=10) or aortic bifurcation (n=5) in 15 patients undergoing robotic RC (n=4) or laparoscopic RC (n=11) at two institutions. SURGICAL PROCEDURE: We performed robotic extended PLND with the proximal extent up to the IMA or aortic bifurcation. The LND was performed starting from the right external iliac, obturator, internal iliac, common iliac, preaortic and para aortic, precaval, and presacral and then proceeding to the left side. The accompanying video highlights our detailed technique. MEASUREMENTS: Median age was 69 yr, body mass index was 26, and American Society of Anesthesiologists class >= 3 was present in 40% of patients. All urinary diversions, including orthotopic neobladder (n=5) and ileal conduit (n=10), were performed extracorporeally. RESULTS AND LIMITATIONS: All 15 procedures were technically successful without need for conversion to open surgery. Median operative time was 6.7h, estimated blood loss was 500 ml, and three patients (21%) required blood transfusion. Median nodal yield in the entire cohort was 31 (range: 15-78). The IMA group had more nodes retrieved (median: 42.5) compared with the aortic bifurcation group (median: 20.5). Histopathology confirmed nodal metastases in four patients (27%), including three patients in the IMA group and one patient in the aortic bifurcation group. Perioperative complications were recorded in six cases (40%). During a median follow-up of 13 mo, no patient developed local or systemic recurrence. Limitations of the study include its retrospective design and small cohort of patients. CONCLUSIONS: High extended PLND during laparoscopic or robotic RC is technically feasible. Longer survival data in a larger cohort of patients are necessary to determine the proper place for robotic and laparoscopic surgery in patients undergoing RC for high-risk bladder cancer. PMID- 22036643 TI - The role of sipuleucel-T in therapy for castration-resistant prostate cancer: a critical analysis of the literature. AB - CONTEXT: Sipuleucel-T, an autologous antigen-presenting cell vaccine loaded with prostate acid phosphatase conjugated with granulocyte-macrophage colony stimulating factor (GM-CSF), yielded a survival advantage in men with metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: Critically analyze the role of sipuleucel-T in therapy for mCRPC. EVIDENCE ACQUISITION: A systematic review of the literature was performed in June 2011 using Medline and an abstract search of major cancer conferences. The search strategy included the terms sipuleucel-T, APC-8015, castration-resistant, prostate cancer, and immunotherapy. EVIDENCE SYNTHESIS: The era of targeted immunotherapy was initiated with the regulatory approval in 2010 of sipuleucel-T for asymptomatic and minimally symptomatic mCRPC. The median survival was prolonged by 4.1 mo (25.8 vs 21.7 mo; hazard ratio: 0.78; 95% confidence interval, 0.61-0.98; p=0.03), coupled with an improvement in 3-yr survival (31.7% vs 23.0%). Outcomes were characterized by the lack of tumor regression or delay in progression. Further development is proceeding in earlier stages of prostate cancer and in the context of a host of emerging agents. CONCLUSIONS: The addition of sipuleucel-T, an immunotherapeutic agent, to the armamentarium represents a paradigm shift in therapy for mCRPC. The rational combination and proper sequencing of sipuleucel-T with other newly approved agents (abiraterone acetate, cabazitaxel) and emerging agents (MDV3100, TAK-700, ipilimumab) will be important to evaluate. PMID- 22036644 TI - Academic ranking score: a publication-based reproducible metric of thought leadership in urology. AB - BACKGROUND: Hospital rankings have become integral to the marketing strategies of many health care systems. Methodology used in compiling these lists appears highly flawed. OBJECTIVE: To improve on current hospital ranking systems and to develop a more meaningful measure of a urology department's contribution to the field, we developed an academic ranking score (ARS) based on publicly available data. DESIGN, SETTING, AND PARTICIPANTS: An active faculty list was assembled for each department. A list of all publications from each department from 2005 to 2010 was then compiled. Only publications with faculty members as first or last author were considered. The ARS was then derived by identifying the number of publications within an institution, normalized by the impact factor of the peer reviewed journal in which the publication appeared. MEASUREMENTS: The 2010 U.S. News & World Report (USNWR) urology list was reranked based on ARS and compared with the USNWR rank list. ARS was also calculated for several leading European urologic centers. RESULTS AND LIMITATIONS: A total of 6437 urologic publications were indexed to calculate the ARS. Two of the top three programs in the USNWR rankings dropped out of the top 10. The top 10 academically ranked programs increased or decreased an average of >5 positions (range: 0-17). No correlation was seen between programs ranked in the top 10 by USNWR and our objective ARS method (Spearman rho: -0.1; p=0.75). Because ARS only includes first- or last author publications for faculty with clinical duties, ARS likely excludes basic science contributions and contributions from nonclinical faculty. CONCLUSIONS: Ranking of urology departments through quantification of each program's recent academic contribution, as captured by the ARS, differs substantially from rankings developed by USNWR. Integration of such objective measures into an overall urology program ranking system would replace current subjective opinions marred by historical biases with up-to-date merit-based assessments. PMID- 22036645 TI - Perioperative comparison of robotic assisted laparoendoscopic single-site (LESS) pyeloplasty versus conventional LESS pyeloplasty. AB - BACKGROUND: Conventional laparoendoscopic single-site (C-LESS) pyeloplasty is technically challenging due to instrument clashing, loss of triangulation, and difficulty sewing. Application of the da Vinci S or Si robotic platforms could potentially overcome these challenges. OBJECTIVE: Compare our initial experience with robotic assisted laparoendoscopic single-site (R-LESS) pyeloplasty to our latter experience with C-LESS pyeloplasty (ie, after the initial 15 patients). DESIGN, SETTING, AND PARTICIPANTS: This single-institution retrospective observational cohort study involved consecutive patients who presented with symptomatic ureteropelvic junction obstruction and who were deemed suitable for single-incision pyeloplasty by the treating surgeon. MEASUREMENTS: Demographic, clinical, perioperative, and early postoperative comparative outcomes. RESULTS AND LIMITATIONS: Ten patients each underwent R-LESS or C-LESS pyeloplasty by a single surgeon between March 2009 and July 2011. For R-LESS and C-LESS groups, age, gender distribution, body mass index, proportion of patients with prior abdominal surgery, estimated blood loss, and hospital length of stay were statistically similar. Mean operative time was significantly longer for R-LESS (226 vs 188 min; p=0.007). C-LESS pyeloplasty alone required an accessory port for the anastomosis in 10 of 10 cases. Two conversions to standard laparoscopy and two postoperative complications occurred in 3 of 10 patients in the C-LESS group, compared with no conversions and one postoperative complication in the R LESS group (p=0.26). Study limitations are a retrospective design, a modest number of patients, and a lack of quantification of subjective outcomes such as instrument clashing and maneuverability. CONCLUSIONS: Adaptation of the da Vinci Si robotic surgical platform to laparoendoscopic single-site pyeloplasty appears to reduce the physical learning curve for this complex procedure. Future prospective, comprehensive evaluation of additional outcomes including subjective parameters, cosmesis, and longer term functional outcomes will help better define its role in minimally invasive dismembered pyeloplasty and better estimate its associated learning curve. PMID- 22036647 TI - Cell aging-induced methionine oxidation causes an autocrine to paracrine shift of the pheromone activity in the protozoan ciliate, Euplotes raikovi. AB - Ciliates of the genus Euplotes rely on the autocrine (self) and paracrine (non self) activities of their water-borne protein pheromones to control the two fundamental phenomena of their life cycle, i.e. vegetative (mitotic) growth and sex manifested as cell union in mating pairs. We observed that cell aging determines the synthesis of increasing concentrations of pheromones that are oxidized at the level of methionine residues which are more exposed on the molecular surface. The oxidized form of the E. raikovi pheromone Er-1 was purified and its interactions with its source cells were shown no longer to be of autocrine type directed to promote cell growth, but changed to interactions of the paracrine type directed to induce cell unions in mating pairs of the selfing type (i.e. involving genetically identical cells). These pairs generate viable offspring, like pairs formed between genetically different cells. It was therefore concluded that aging cells may paradoxically gain beneficial effects from the synthesis of oxidized forms of their pheromones. By undergoing mating in response to the interactions with these forms, they can re-initiate a new life cycle and, in fact, rejuvenate. PMID- 22036648 TI - Coordinated regulation of caveolin-1 and Rab11a in apical recycling compartments of polarized epithelial cells. AB - Recent studies have identified caveolin-1, a protein best known for its functions in caveolae, in apical endocytic recycling compartments in polarized epithelial cells. However, very little is known about the regulation of caveolin-1 in the endocytic recycling pathway. To address this question, in the current study we compared the relationship between compartments enriched in sub-apical caveolin-1 and Rab11a, a well-defined marker of apical recycling endosomes, using polarized MDCK cells as a model. We show that caveolin-1-containing vesicles define a compartment that partially overlaps with Rab11a, and that the distribution of subapical caveolin-1 and Rab11a shows a similar dependence on microtubule disruption. Mutants of the Rab11a effector, Rab11-FIP2 also altered the localization of caveolin-1. These findings indicate that caveolin-1 is coordinately regulated with Rab11a within the apical recycling system of polarized epithelial cells, suggesting that the two proteins are components of the same pathway. PMID- 22036649 TI - Chemokines in tumor development and progression. AB - Chemokines were originally identified as mediators of the inflammatory process and regulators of leukocyte trafficking. Subsequent studies revealed their essential roles in leukocyte physiology and pathology. Moreover, chemokines have profound effects on other types of cells associated with the inflammatory response, such as endothelial cells and fibroblasts. Thus, chemokines are crucial for cancer-related inflammation, which can promote tumor development and progression. Increasing evidence points to the vital effects of several chemokines on the proliferative and invasive properties of tumor cells. The wide range of activities of chemokines in tumorigenesis highlights their roles in tumor development and progression. PMID- 22036650 TI - Increased glyoxalase I levels inhibit accumulation of oxidative stress and an advanced glycation end product in mouse mesangial cells cultured in high glucose. AB - Chronic high glucose levels lead to the formation of advanced glycation end products (AGEs) as well as AGE precursors, such as methylglyoxal (MG) and glyoxal, via non-enzymatic glycation reactions in patients with diabetic mellitus. Glyoxalase 1 (GLO-1) detoxifies reactive dicarbonyls that form AGEs. To investigate the interaction between AGEs and GLO-1 in mesangial cells (MCs) under diabetic conditions, AGE levels and markers of oxidative stress were measured in GLO-1-overexpressing MCs (GLO-1-MCs) cultured in high glucose. Furthermore, we also examined levels of high glucose-induced apoptosis in GLO-1-MCs. In glomerular MCs, high glucose levels increased the formation of both MG and argpyrimidine (an MG-derived adduct) as well as GLO-1 expression. GLO-1-MCs had lower intracellular levels of MG accumulation, 8-hydroxy-deoxyguanosine (an oxidative DNA damage marker), 4-hydroxyl-2-nonenal (a lipid peroxidation product), and nitrosylated protein (a marker of oxidative-nitrosative stress) compared to control cells. Expression of mitochondrial oxidative phosphorylation complexes I, II, and III was also decreased in GLO-1-MCs. Furthermore, fewer GLO 1-MCs showed evidence of apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick labeling assay, and activation of both poly (ADP ribose) polymerase 1 cleavage and caspase-3 was lower in GLO-1-MCs than in control cells cultured in high glucose. These results suggest that GLO-1 plays a role in high glucose-mediated signaling by reducing MG accumulation and oxidative stress in diabetes mellitus. PMID- 22036651 TI - Antiviral interactions of combinations of highly potent 2,4(1H,3H) pyrimidinedione congeners and other anti-HIV agents. AB - Structure-activity relationship evaluation of seventy-four 2,4(1H,3H) pyrimidinedione derivatives identified seven lead compounds based on anti-HIV-1 potency, extended range of action to include HIV-2, virus entry inhibition, reverse transcriptase inhibition, and lack of cytotoxicity to human cells. The selected pyrimidinedione congeners are highly active inhibitors of HIV-1 with EC(50) values ranging from 0.6 to 2 nM in CEM-SS cells infected with laboratory derived viruses, 11-20 nM in fresh human PBMCs infected with subtype B (HT/92/599) virus, and 2-7 nM in PBMCs infected with the clinical subtype C (ZA/97/003) virus. Combination antiviral assays were performed using the laboratory adapted RF strain of HIV-1 in CEM-SS cells and with a clade B and C low passage clinical isolate in fresh human peripheral mononuclear cells and the compound interactions were analyzed using MacSynergy II. The seven pyrimidinedione compounds resulted in additive to synergistic interactions in combination with entry and fusion inhibitors, nonnucleoside and nucleoside reverse transcriptase inhibitors, and the protease inhibitors. No evidence of antagonistic antiviral activity or synergistic cytotoxicity was detected with the combinations of compounds tested. The dual mechanism of action of the pyrimidinediones resulting in inhibition of both virus entry and reverse transcription suggests excellent potential of these lead pyrimidinediones as candidates for combination therapy with other approved HIV inhibitors of varying mechanism of action. PMID- 22036652 TI - Determination of moisture content in relation to thermal behaviour and plasticization of Eudragit RLPO. AB - Coalescence of polymer particles on thermal treatment plays an important role in effective control of drug release from these matrix systems. The water content of the polymer may influence coalescence since it is well established that sorbed water may act as a plasticizer, or cause other changes in mechanical properties. However, these effects depend on the amount and type (plasticizing/nonplasticizing) of water present. The purpose of this study was to determine the accuracy of different methods used to determine moisture content of a polymer (Eudragit RLPO) and to determine the types water present. The polymer powder was stored at various relative humidities (33, 56, 75, 94%). Four water determination methods, [weight loss on drying, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Karl Fischer titration (KFT)] were utilized to determine moisture content. DSC was used to study the thermal behaviour of moist and dry samples. The Gordon-Taylor equation was used to calculate the amount of plasticizing water. Scanning electron microscopy was employed to examine the morphology of the polymer particles after thermal analyses. It is concluded that KFT accurately determines the total water content but that the thermal methods underestimate total water content. However KFT does not indicate the type of water present. The Gordon-Taylor model suggests that only about 25% of the water in the polymer containing 10% water was acting as a plasticizer. Complementary methods should be used to measure the water content of pharmaceutical polymers. PMID- 22036653 TI - Influence of the lactose grade within dry powder formulations of fluticasone propionate and terbutaline sulphate. AB - Dry powder formulations are often composed of fine drug particles and coarser carrier particles, typically alpha-lactose monohydrate. However, the performance of a powder formulation may be highly dependent on the lactose quality and source. This study investigated the characteristics of lactose that influence the drug-to-carrier interaction and the performance of lactose-based dry powder inhaler formulations. The selected lactoses differed in the preparation processes and the content of fine lactose particles. Efficiency testing was done using fluticasone propionate and terbutaline sulphate as model drugs. Inverse gas chromatography was used to determine the surface heterogeneity distribution of different energy sites of the lactose and to understand the mechanism by which the fine carrier particles can improve the performance of dry powder inhalers. To assess the adhesion of respirable-sized drug to carrier particles, a simple method was developed based on aspiration and considering the whole blend as it is used in dry powder inhalers. When the percentage of fine lactose is high, a lower quantity of drug adheres to the lactose and/or the adhesion force is also lower. This was confirmed by the aerosolization assays done in the TSI (twin stage impinger). A correlation was observed between adhesion characteristics and inertial impaction. For both drugs, the fine particle fractions were highest in blends that present a greater proportion of lactose fine particles. A fairly good correlation between the fine particle fractions of both drugs and the peak max value and the AUC (area under curve) were found by inverse gas chromatography. With higher fine particle fraction values, which correspond to higher content of fines, the peak maxima determined by inverse gas chromatography were shifted to higher adsorption potentials, which supports the agglomeration hypothesis. PMID- 22036655 TI - A woman with headache and ptosis. PMID- 22036654 TI - The use of chemical restraints reduces agitation in patients transported by emergency medical services. AB - BACKGROUND: Agitated patients are the primary source of injury to patients and providers during ambulance transport. OBJECTIVE: Our primary hypothesis was that the addition of a chemical restraint agent (midazolam) to a restraint protocol would reduce agitation to a greater extent than a restraint protocol with physical restraint alone. METHODS: The local emergency medical services restraint protocol (RP) was implemented on October 1, 2006. It included a form for data collection about each restrained patient. On April 1, 2007, chemical restraint (CR) using midazolam in addition to physical restraints was made available through the RP, and paramedics were educated in its use. Transported patients were divided into pre-CR and post-CR. The post-CR group was split into those who received and those who did not receive midazolam. Agitation was measured on a validated agitation behavior scale with a parametric (Rasch) adjustment. RESULTS: There were 96 patients in the pre-CR group and 522 patients in the post-CR group. Forty-three percent of the pre-CR group and 49% of the post-CR group had a decrease in agitation during transport (NS). Of the 522 in the post-CR group, 110 were physically restrained and given midazolam (21%) and 412 were physically restrained without midazolam (79%). There was a significantly greater decrease in agitation scores (-17 +/- 21 vs. -7 +/- 17) in the subjects receiving midazolam compared to those who did not. CONCLUSION: If available, CR is used in about 20% of restrained patients. When CR is used, there is a decrease in the subject's agitation. PMID- 22036656 TI - A case of an unusual hernia associated with gastrointestinal bleeding. AB - BACKGROUND: Acute upper gastrointestinal (GI) bleed is a well-known presentation to the emergency department (ED) frequently accompanied by hematemesis. We describe the case of a patient with abdominal content herniation into the chest wall with a recent history of coronary artery bypass graft presenting with acute onset of hematemesis. OBJECTIVES: To present an exceedingly rare herniation of abdominal contents into the chest wall that was accompanied by hematemesis and to present the rare visual findings inherent in this pathology. CASE REPORT: A 65 year-old man presented to the ED vomiting large amounts of blood upon presentation, compromising hemodynamic stability and prompting emergent resuscitation. The patient's presentation was complicated by a large 30 * 40-cm anterior chest wall mass extending 2 cm inferior to the sternal notch expanding with each episode of hematemesis. Computed tomography after stabilization revealed a large ventral hernia extending into the chest wall, containing small and large bowel. We suspected this large, unusual hernia to be the underlying cause of the patient's GI bleeding. CONCLUSION: The emergency physician must be able to assess hemodynamic stability of an upper GI bleed and resuscitate the unstable patient if warranted. Diagnosis is to be subsequently determined after stabilization. PMID- 22036657 TI - Development of proteomic tools to study protein adsorption on a biomaterial, titanium grafted with poly(sodium styrene sulfonate). AB - It is known that protein adsorption is the initial interaction between implanted biomaterials and biological environment. Generally, a complex protein layer will be formed on material surfaces within a few minutes and the composition of this layer at the interface determines the biological response to the implanted material, and therefore the long-term compatibility of the biomaterial. Despite different techniques exist to observe protein adsorption on biomaterials, none of them led to the identification of adsorbed proteins. In this paper, we report a chromatographic technique coupled to proteomics to analyse and identify proteins from complex biological samples adsorbed on biomaterial surfaces. This approach is based on (1) elaboration of the chromatographic support containing the biomaterial (2) a chromatography step involving adsorption of proteins on the biomaterial (3) the high-resolution separation of eluted proteins by 2-DE gel and (4) the identification of proteins by mass spectrometry. Experiments were performed with proteins from platelets rich plasma (PRP) adsorbed on a biomaterial which consist in titanium bioactivated with PolyNaSS. Our results show that chromatographic approach combined to 2-DE gels and mass spectrometry provides a powerful tool for the analysis and identification of proteins adsorbed on various surfaces. PMID- 22036658 TI - Urinary metanephrines by liquid chromatography tandem mass spectrometry: using multiple quantification methods to minimize interferences in a high throughput method. AB - Determination of urinary metanephrines is requested frequently for the differential diagnosis and monitoring of pheochromocytoma. Although numerous methods have been developed, interferences are common and hinder most available assays. This study describes the development, validation and implementation of a reliable high-throughput LC-MS/MS method for the measurement of metanephrine and normetanephrine in urine. Metanephrine and normetanephrine were isolated from urine samples subjected to acid hydrolysis using solid phase extraction on a mixed mode cation exchange sorbent in 96-well format. The extracts were injected directly onto a Restek perfluorophenyl column and separated isocratically in 0.2% formic acid in 5% methanol with a gradient cleanout step to 50% methanol. Detection was accomplished using an API 3200 triple quadrupole mass spectrometer with electrospray ionization in positive mode. Data were acquired in multiple reaction monitoring mode. Three transitions were monitored for metanephrine and its deuterated internal standard; two transitions were monitored for normetanephrine and its deuterated internal standard. Two quantification methods were used to address metanephrine interferences without reducing throughput. The method was linear to 15,000 nmol/L. The limits of detection and quantification were 2.5 and 10 nmol/L, respectively. Within run, between-day and total imprecision values were at or below 1.9%, 2.5% and 2.7% for both analytes. The method correlated well with our previously used GC-MS method. Injection-to injection time was 6 min. The validated LC-MS/MS method for measurement of metanephrine and normetanephrine in urine specimens was placed into service in August 2010 and has performed exceptionally well. PMID- 22036659 TI - Thermal treatment of the bacteriophage lysate of Klebsiella pneumoniae B5055 as a step for the purification of capsular depolymerase enzyme. AB - The lytic bacteriophage which produces the hydrolase enzyme capable of depolymerizing exopolysaccharide of Klebsiella pneumoniae and of other bacteria was isolated earlier. In this study, a simple method of depolymerase purification from the phage lysate by dissociating the enzyme from the phage particle was developed. The bacteriophage showed a relatively smaller plaque size surrounded by a wide halo indicating a depolymerase action on the capsular polysaccharide of K. pneumoniae B5055. The depolymerase activity was associated predominantly with the phage particles. Different methods have been used by various researchers to dissociate the enzyme associated with phage particles either by exposure to chemicals or by altering the environmental conditions. In this study, the potential application of thermal treatment of the bacteriophage lysate was evaluated as a step for the purification of depolymerase in comparison to the mild acid treatment method of Rieger et al. (1975). The results showed that the relative thermal stability of phage depolymerase at 60 degrees C for 30min was the basis for harvesting the enzyme leading to disintegration of all phage particles in the lysate. Both thermal and mild acid treatment resulted in comparable enzyme levels, however; mild acid treatment appeared to be cumbersome and cause chemical contamination. PMID- 22036660 TI - Viral elution and concentration method for detection of influenza A viruses in mud by real-time RT-PCR. AB - The role of environmental reservoirs in avian influenza virus (AIV) transmission has been investigated during AIV-associated outbreaks. To date, no method has been defined for detection of AIV from mud samples. A procedure using elution and polyethylene glycol (PEG) concentration steps was designed to detect AIV by RT PCR from 42g of raw mud, corresponding to 30g of the solid fraction of mud. RNA was recovered with MagMAX AI/ND Viral RNA Isolation kit (Ambion, Austin, TX). Three elution buffers were studied and viral recoveries higher than 29% were yielded by elution with a 10% beef extract solution (pH 7). The overall method showed that, under some conditions, virus was not detectable in PEG samples, whereas viruses were detected in the elution fractions. PCR curves were improved significantly by running the amplification reaction with a mixture containing a PCR additive for inhibitor removal, such as T4 gene 32 protein (Gp32), although PCR inhibitors from mud were removed partially from PEG samples. A theoretical detection threshold of 5*10(5) RNA copies of H5N1 virus per 30g of solid mud could be obtained by elution. The overall method has proved successful for detecting H5N1 virus contamination of mud specimens collected during outbreak investigations of avian influenza in Cambodia. PMID- 22036661 TI - Is the new seventh AJCC/UICC staging system appropriate for patients with gastric cancer? AB - BACKGROUND: The purpose of this study was to compare the clinical usefulness of the seventh Union Internationale Contre le Cancer/American Joint Committee on Cancer (AJCC/UICC) staging system vs the sixth AJCC/UICC staging system in patients with gastric cancer. STUDY DESIGN: Included were 1,799 patients who underwent surgery for gastric cancer between January 2001 and June 2005 at the National Cancer Center (South Korea). For the sixth and seventh AJCC/UICC staging systems, survival outcomes stratified by stage, by T classification, and by N classification were summarized using Kaplan-Meier curves and compared statistically using a log rank test; survival differences were quantified using hazard ratios estimated from a Cox regression model. The 2 systems were compared in terms of prognostic performances using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion (AIC) in the Cox regression analysis. RESULTS: Significant survival differences between each stage were not found using the seventh staging system, especially for stages IB, IIA, and IIB (p = 0.14 and p = 0.11). The sixth staging system had higher linear trend chi-square score and likelihood ratio chi-square score, which means better discriminatory ability, monotonicity, and homogeneity, and had smaller AIC, which indicates better optimistic prognostic stratification, especially in the N classification. The modified staging system combining the T classification of the seventh AJCC/UICC system and the N classification of the sixth system showed better prognostic performance compared with each separate version (sixth or seventh) of the staging system. CONCLUSIONS: The seventh AJCC/UICC staging system is not more clinically useful than the sixth system in surgically treated patients with gastric cancer because of an inappropriate N classification. A new TNM system is required with a different N classification. PMID- 22036662 TI - Laparoscopic distal gastrectomy with an intracorporeal gastroduodenostomy using a circular stapler. PMID- 22036663 TI - Neuroplastin: cell adhesion molecule and signaling receptor. AB - Neuroplastin (Np) is a glycoprotein that belongs to the immunoglobulin superfamily of cell adhesion molecules. It exists in two isoforms, Np55 and Np65, named according to their apparent molecular weights. Neuroplastins were first identified as synapse-specific proteins, but subsequent findings have shown that Np65 is indeed expressed only in the brain, whereas Np55 is found in wide range of tissues. Since their discovery, the knowledge of Nps expanded, implicating them in various processes, including neuronal differentiation and synaptic plasticity. Here, we will review the Np structure and mechanisms involved in Np signaling and discuss the functions of Nps in the nervous system. PMID- 22036664 TI - Landing technique affects knee loading and position during athletic tasks. AB - Anterior cruciate ligament (ACL) injuries have been reported to occur with the ankle in a dorsiflexed position at initial contact. Few studies have attempted to quantify the biomechanical parameters related with such landing patterns during athletic tasks. OBJECTIVES: The purpose of this study was to evaluate the effects that two landing techniques have in lower extremity biomechanics while performing two tasks. DESIGN: Single-group repeated measures design. METHODS: Twenty female soccer athletes from a Division I institution performed two landing techniques (forefoot and rearfoot) during two unanticipated tasks (sidestep cutting and pivot). Repeated measures analyses of variance were conducted to assess differences in the kinematic and kinetic parameters between landing techniques for each task. RESULTS: The forefoot landing technique had significantly higher internal knee adductor moment than the rearfoot for both the pivot and sidestep cutting task (p<0.001 and p=0.003, respectively). For the sidestep cutting task, participants had increased knee valgus angle with the rearfoot, whereas for the pivot they had increased knee valgus with the forefoot landing technique (p<0.05). CONCLUSIONS: The results of this study highlighted that there are inherent differences in biomechanical outcomes between foot-landing techniques. The forefoot landing technique increasingly affects knee adduction moment loading, which can potentially place a higher strain on the ACL. Essentially, the demands of the landing technique on lower extremity biomechanics (e.g., hip and knee) are task dependent. PMID- 22036665 TI - Recurrence and long-term maternal health risks of hypertensive disorders of pregnancy: a population-based study. AB - OBJECTIVE: The purpose of this study was to investigate the recurrence risk of hypertensive disorders in subsequent pregnancies and to explore the associations among hypertensive disorders of pregnancy and maternal cardiovascular risk factor profile and the development of cardiovascular diseases later in life. STUDY DESIGN: We used population-based, cross-sectional data from the fourth survey of the Tromso Study. RESULTS: Preeclampsia in the first pregnancy increased the risk of recurrence in later pregnancies (relative risk, 6.6; 95% confidence interval, 5.5-7.9) compared with a normotensive first pregnancy. Women with a history of preeclampsia or nonproteinuric hypertension had an unfavorable cardiovascular risk profile. Hypertension was prevalent in 25% and 28% of the women, respectively. The carotid artery intima-media thickness and total carotid plaque area were significantly larger in women with previous preeclampsia. CONCLUSION: A strong association between hypertensive disorders of pregnancy and an increased risk of atherosclerosis and cardiovascular diseases was demonstrated by the assessment of risk factors that can be potentially modified. PMID- 22036666 TI - Cervical necrotizing fasciitis of odontogenic origin involving the temporal region--a case report. AB - Necrotizing fasciitis (NF) is a soft-tissue infection, usually polymicrobial, that causes necrosis of fascia and subcutaneous tissue while sparing skin and muscle. We report a case of cervical NF complicating dental infection in a 50 year-old woman, who presented with infection involving mucosa of the right mandible and temporal muscle, and masticator spaces, requiring extensive surgery and antibiotic therapy. Prompt diagnosis and immediate aggressive surgical debridement of all compromised tissues are critical to reducing morbidity and mortality in these rapidly progressive infections. PMID- 22036667 TI - Informed consent and patient registry for the rare disease community: Editorial. PMID- 22036668 TI - Multifunctional magnetic-plasmonic nanoparticles for fast concentration and sensitive detection of bacteria using SERS. AB - Multifunctional magnetic-plasmonic Fe(3)O(4)-Au core-shell nanoparticles (Au MNPs) were prepared for simultaneous fast concentration of bacterial cells by applying an external point magnetic field, and sensitive detection and identification of bacteria using surface-enhanced Raman spectroscopy (SERS). We demonstrated that a spread of a 10 MUL drop of a mixture of 10(5) cfu/mL bacteria and 3 MUg/mL Au-MNPs on a silicon surface can be effectively condensed into a highly compact dot within 5 min by applying an external point magnetic field, resulting in 60 times more concentrated bacteria in the dot area than on the spread area without concentration. Surrounded by dense uniformly packed Au-MNPs, bacteria can be sensitively and reproducibly detected directly using SERS. The principle component analysis (PCA) showed that three different Gram-negative bacterial strains can be clearly differentiated. We also demonstrated that the condensed multifunctional Au-MNPs dot can be used as a highly sensitive SERS active substrate and a limit of detection better than 0.1 ppb was obtained in detection of small molecules such as 4-mercaptopyrine. This novel platform significantly simplifies the concentration and detection process, which holds great promise for applications in food safety, environmental monitoring, medical diagnoses, and chemical and biological threat detections. PMID- 22036669 TI - Monitoring extracellular K+ flux with a valinomycin-coated silicon nanowire field effect transistor. AB - A silicon nanowire field-effect transistor (SiNW-FET) coated with a polyvinyl chloride (PVC) membrane containing valinomycin (VAL) was employed as a biosensor (referred to as VAL-PVC/SiNW-FET) to detect the K(+)-efflux from live chromaffin cells. The detection sensitivity of K(+) with the VAL-PVC/SiNW-FET covers a broad range of concentrations from 10(-6) to 10(-2) M. The apparent association constants between VAL and Li(+), Na(+), K(+), and Cs(+) in Tris buffer solution were determined to be 67+/-42, 120+/-23, 5974+/-115, and 4121+/-140 M(-1), respectively. By culturing chromaffin cells on the VAL-PVC/SiNW-FET, the conductance was significantly increased by nicotine stimulation in a bath buffer without Na(+). The K(+) concentration at the cell surface was determined to be ~20 MUM under the stimulation of 5 mM nicotine. These results demonstrate that the VAL-PVC/SiNW-FET is sensitive and selective to detect the released K(+) from cells and is suitable for applications in cellular recording investigations. PMID- 22036670 TI - A comparative transmission electron microscopy study of titanium dioxide and carbon black nanoparticles uptake in human lung epithelial and fibroblast cell lines. AB - Several studies suggest that the biological responses induced by manufactured nanoparticles (MNPs) may be linked to their accumulation within cells. However, MNP internalisation has not yet been sufficiently characterised. Therefore, the aim of this study was to compare the intracellular uptake of three different MNPs: two made of carbon black (CB) and one made of titanium dioxide (TiO(2)), in 16HBE bronchial epithelial cells and MRC5 fibroblasts. Transmission electron microscopy was used to evaluate the intracellular accumulation. Different parameters were analysed following a time and dose-relationship: localisation of MNPs in cells, percentage of cells having accumulated MNPs, number of aggregated MNPs in cells, and the size of MNP aggregates in cells. The results showed that MNPs were widely and rapidly accumulated in 16HBE cells and MRC5 fibroblasts. Moreover, MNPs accumulated chiefly as aggregates in cytosolic vesicles and were absent from the mitochondria or nuclei. CB and TiO(2) MNPs had similar accumulation patterns. However, TiO(2) aggregates had a higher size than CB aggregates. Intracellular MNP accumulation was dissociated from cytotoxicity. These results suggest that cellular uptake of MNPs is a common phenomenon occurring in various cell types. PMID- 22036672 TI - Focal adhesion kinase regulation of endothelial barrier function, apoptosis, and neovascularization. PMID- 22036671 TI - The interdomain linker region of HIV-1 capsid protein is a critical determinant of proper core assembly and stability. AB - The HIV-1 capsid protein consists of two independently folded domains connected by a flexible peptide linker (residues 146-150), the function of which remains to be defined. To investigate the role of this region in virus replication, we made alanine or leucine substitutions in each linker residue and two flanking residues. Three classes of mutants were identified: (i) S146A and T148A behave like wild type (WT); (ii) Y145A, I150A, and L151A are noninfectious, assemble unstable cores with aberrant morphology, and synthesize almost no viral DNA; and (iii) P147L and S149A display a poorly infectious, attenuated phenotype. Infectivity of P147L and S149A is rescued specifically by pseudotyping with vesicular stomatitis virus envelope glycoprotein. Moreover, despite having unstable cores, these mutants assemble WT-like structures and synthesize viral DNA, although less efficiently than WT. Collectively, these findings demonstrate that the linker region is essential for proper assembly and stability of cores and efficient replication. PMID- 22036673 TI - Influence of blood flow on arteriolar wall-to-lumen ratio in the human retinal circulation in vivo. AB - OBJECTIVE: We hypothesized that blood flow impacts on arteriolar wall-to-lumen ratio and that vasodilatory capacity is negatively related to arteriolar wall-to lumen ratio in the human retinal vascular bed. METHODS: The study cohort comprised 141 non-diabetic untreated male patients with (n=52) or without (n=89) arterial hypertension but without evidence for cardiovascular disease. Retinal capillary blood flow (RCF) before and after exposure to flicker light and to infusion of nitric oxide (NO) synthase inhibitor N-monomethyl-L-arginine (L NMMA), and parameters of retinal arteriolar morphology, e.g. wall-to-lumen ratio, were assessed non-invasively and in vivo by scanning laser Doppler flowmetry. RESULTS: The study cohort was grouped according to the median RCF into two groups. Patients with RCF above the median revealed lower wall-to-lumen ratio (0.30 +/- 0.1 vs 0.34 +/- 0.1 (-), P adjusted=0.023) compared to patients with RCF equal or below the median. In addition, RCF was negatively related to wall-to lumen ratio independently of cardiovascular risk factors (beta=-0.224, P=0.026). In parallel, the decrease of RCF to L-NMMA infusion was greater in patients with RCF above the median compared to the counter group (-8.95 +/- 11 vs. 0.35 +/- 15 (%), P adjusted <0.001). The increase in RCF to flicker light exposure was negatively related to wall-to-lumen ratio in hypertensive but not in normotensive or all patients (r=-0.292, P=0.047, r=-0.035, P=0.746 and r=-0.126, P=0.144, respectively). CONCLUSIONS: In the retinal circulation blood flow impacts on arteriolar wall-to-lumen ratio. Basal NO activity might modulate blood flow and arteriolar morphological changes. In hypertensive, but not in normotensive patients, the vasodilatory capacity is negatively related to arteriolar wall-to lumen ratio in the human retinal vascular bed. PMID- 22036674 TI - Maxadilan, the Lutzomyia longipalpis vasodilator, drives plasma leakage via PAC1 CXCR1/2-pathway. AB - Experiments were designed to determine if the vasodilatory peptides maxadilan and pituitary adenylate cyclase-activating peptide (PACAP-38) may cause plasma leakage through activation of leukocytes and to what extent these effects could be due to PAC1 and CXCR1/2 receptor stimulation. Intravital microscopy of hamster cheek pouches utilizing FITC-dextran and rhodamine, respectively, as plasma and leukocyte markers was used to measure arteriolar diameter, plasma leakage and leukocyte accumulation in a selected area (5mm(2)) representative of the hamster cheek pouch microcirculation. Our studies showed that the sand fly vasodilator maxadilan and PACAP-38 induced arteriolar dilation, leukocyte accumulation and plasma leakage in postcapillary venules. The recombinant mutant of maxadilan M65 and an antagonist of CXCR1/2 receptors, reparixin, and an inhibitor of CD11b/CD18 up-regulation, ropivacaine, inhibited all these effects as induced by maxadilan. Dextran sulfate, a complement inhibitor with heparin-like anti-inflammatory effects, inhibited plasma leakage and leukocyte accumulation but not arteriolar dilation as induced by maxadilan and PACAP-38. In vitro studies with isolated human neutrophils showed that maxadilan is a potent stimulator of neutrophil migration comparable with fMLP and leukotriene B(4) and that M65 and reparixin inhibited such migration. The data suggest that leukocyte accumulation and plasma leakage induced by maxadilan involves a mechanism related to PAC1- and CXCR1/2 receptors on leukocytes and endothelial cells. PMID- 22036675 TI - Statistical feature extraction for artifact removal from concurrent fMRI-EEG recordings. AB - We propose a set of algorithms for sequentially removing artifacts related to MRI gradient switching and cardiac pulsations from electroencephalography (EEG) data recorded during functional magnetic resonance imaging (fMRI). Special emphasis is directed upon the use of statistical metrics and methods for the extraction and selection of features that characterize gradient and pulse artifacts. To remove gradient artifacts, we use channel-wise filtering based on singular value decomposition (SVD). To remove pulse artifacts, we first decompose data into temporally independent components and then select a compact cluster of components that possess sustained high mutual information with the electrocardiogram (ECG). After the removal of these components, the time courses of remaining components are filtered by SVD to remove the temporal patterns phase-locked to the cardiac timing markers derived from the ECG. The filtered component time courses are then inversely transformed into multi-channel EEG time series free of pulse artifacts. Evaluation based on a large set of simultaneous EEG-fMRI data obtained during a variety of behavioral tasks, sensory stimulations and resting conditions showed excellent data quality and robust performance attainable with the proposed methods. These algorithms have been implemented as a Matlab-based toolbox made freely available for public access and research use. PMID- 22036676 TI - MRI patterns of atrophy and hypoperfusion associations across brain regions in frontotemporal dementia. AB - Magnetic Resonance Imaging (MRI) provides various imaging modes to study the brain. We tested the benefits of a joint analysis of multimodality MRI data in combination with a large-scale analysis that involved simultaneously all image voxels using joint independent components analysis (jICA) and compared the outcome to results using conventional voxel-by-voxel unimodality tests. Specifically, we designed a jICA to decompose multimodality MRI data into independent components that explain joint variations between the image modalities as well as variations across brain regions. We tested the jICA design on structural and perfusion-weighted MRI data from 12 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and 12 cognitively normal elderly individuals. While unimodality analyses showed widespread brain atrophy and hypoperfusion in the patients, jICA further revealed two significant joint components of variations between atrophy and hypoperfusion across brain regions. The 1st joint component revealed associated brain atrophy and hypoperfusion predominantly in the right brain hemisphere in behavioral variant frontotemporal dementia, and the 2nd joint component revealed greater atrophy relative to hypoperfusion affecting predominantly the left hemisphere in behavioral variant frontotemporal dementia. The patterns are consistent with the clinical symptoms of behavioral variant frontotemporal dementia that relate to asymmetric compromises of the left and right brain hemispheres. The joint components also revealed that that structural alterations can be associated with physiological alterations in spatially separated but potentially connected brain regions. Finally, jICA outperformed voxel-by-voxel unimodal tests significantly in terms of an effect size, separating the behavioral variant frontotemporal dementia patients from the controls. Taken together, the results demonstrate the benefit of multimodality MRI in conjunction with jICA for mapping neurodegeneration, which may lead ultimately to an improved diagnosis of behavioral variant frontotemporal dementia and other forms of neurodegenerative diseases. PMID- 22036677 TI - Multivariate pattern classification reveals differential brain activation during emotional processing in individuals with psychosis proneness. AB - Among the general population, individuals with subthreshold psychotic-like experiences, or psychosis proneness (PP), can be psychometrically identified and are thought to have a 10-fold increased risk of psychosis. They also show impairments in measures of emotional functioning parallel to schizophrenia. Whilst previous studies have revealed altered brain activation in patients with schizophrenia during emotional processing, it is unclear whether these alterations are also expressed in individuals with high PP. Here we used Support Vector Machine (SVM) to perform multivariate pattern classification based on brain activation during emotional processing in 20 individuals with high PP and 20 comparison subjects (low PP). In addition, we performed a standard univariate analysis based on the General Linear Model (GLM) on the same data for comparison. The experimental task involved passively viewing negative and neutral pictures from the International Affective Picture System (IAPS). SVM allowed classification of the two groups with statistically significant accuracy (p=0.017) and identified group differences within an emotional circuitry including the amygdala, insula, anterior cingulate and medial prefrontal cortex. In contrast, the standard univariate analysis did not detect any significant between-group differences. Our results reveal a distributed and subtle set of alterations in brain function within the emotional circuitry of individuals with high PP, providing neurobiological support for the notion of dysfunctional emotional circuitry in this group. In addition, these alterations are best detected using a multivariate approach rather than standard univariate methods. Further application of this approach may aid in characterising people at clinical and genetic risk of developing psychosis. PMID- 22036679 TI - An alternative approach towards assessing and accounting for individual motion in fMRI timeseries. AB - Motion is a significant problem for the analysis of functional MRI data. This manuscript addresses the question of whether an individualized assessment of motion may be informative, and whether it may be beneficial with regard to explaining motion-related variance. Two independent datasets are used to explore and test this hypothesis, from a total of 21 healthy children, performing either no externally-cued task (resting state) or an active listening paradigm (beep story). Translations and rotations are combined into one single, individual measure of total displacement, which is demonstrated to be substantially different between brain regions as a function of their distance from the individual origin. An increasing number of covariates leads to a loss of detection power, but more so on the first than on the second level, and more so in less-powerful designs. Synthetic timeseries are calculated from which the direct effects of motion as well as motion*B0 effects can be isolated, allowing to extract individual timecourses which reflect both direct and indirect motion effects. Including three timecourses from such an individually-derived "motion fingerprint" into first-level statistical analyses explains variance to a similar degree as the commonly-used approach of including the realignment parameters, and performance is statistically equivalent to including the realignment parameters on the second level. A more individualized approach to explaining motion-related variance may therefore be beneficial, depending on the scenario. PMID- 22036678 TI - Spatial homogeneity and task-synchrony of the trial-related hemodynamic signal. AB - There is growing evidence that functional brain images in alert task-engaged subjects contain task-related but stimulus-independent signals in addition to stimulus-evoked responses. It is important to separate these different components when analyzing the neuroimaging signal. Using intrinsic-signal optical imaging combined with electrophysiology we had earlier reported a particular 'trial related signal' in the primary visual cortex (V1) of alert monkeys performing periodic fixation tasks. This signal periodically modulated V1 tissue blood volume, in time with anticipated trial onsets. Unlike visually evoked blood volume changes, however, this signal was present even in total darkness. Further, it could not be predicted by concurrently recorded spiking or local field potentials. Here we use our earlier recording techniques to analyze the spatial distribution of this trial-related signal over our imaged area (10mm square, subdivided into a 16*16 grid, i.e. at 625 MUm resolution). We show that the signal is spatially coherent and essentially homogeneous over the imaged region and fails to be predicted by concurrent electrode recordings even at the resolution of a single grid square at the electrode tip. As a corollary we show that the signal is critically linked to the animals' engagement in a task. Not only does the trial-related signal entrain accurately and precisely to any task timing at which the animal was willing to perform; the signal also loses the entrained trial-locked pattern dramatically, within a single trial, when the animal stops performing correctly. Thus the signal is very unlikely to be an ongoing task-independent vascular oscillation. These findings will help categorize the likely distinct varieties of non-stimulus-related signals evoked during behavioral tasks, and lead to a further understanding of the elements comprising the net neuroimaging response. PMID- 22036680 TI - Paired pulse depression in the somatosensory cortex: associations between MEG and BOLD fMRI. AB - Interpretation of the blood oxygen level dependent (BOLD) response measured using functional magnetic resonance imaging (fMRI) requires an understanding of the underlying neuronal activity. Here we report on a study using both magnetoencephalography (MEG) and BOLD fMRI, to measure the brain's functional response to electrical stimulation of the median nerve in a paired pulse paradigm. Interstimulus Intervals (ISIs) of 0.25, 0.5, 0.75, 1.0, 1.5 and 2.0 s are used to investigate how the MEG detected neural response to a second pulse is affected by that from a preceding pulse and if these MEG modulations are reflected in the BOLD response. We focus on neural oscillatory activity in the beta-band (13-30 Hz) and the P35m component of the signal averaged evoked response in the sensorimotor cortex. A spatial separation of beta ERD and ERS following each pulse is demonstrated suggesting that these two effects arise from separate neural generators, with ERS exhibiting a closer spatial relationship with the BOLD response. The spatial distribution and extent of BOLD activity were unaffected by ISI, but modulations in peak amplitude and latency were observed. Non-linearities in both induced oscillatory activity ERS and in the signal averaged evoked response are found for ISIs of up to 2s when the signal averaged evoked response has returned to baseline, with the P35m component displaying paired pulse depression effects. The beta-band ERS magnitude was modulated by ISI, however the ERD magnitude was not. These results support the assumption that BOLD non-linearity arises not only from a non-linear vascular response to neural activity but also a non-linear neural response to the stimulus with ISI up to 2 s. PMID- 22036681 TI - Magnetic susceptibility anisotropy of human brain in vivo and its molecular underpinnings. AB - Frequency shift of gradient-echo MRI provides valuable information for assessing brain tissues. Recent studies suggest that the frequency and susceptibility contrast depend on white matter fiber orientation. However, the molecular underpinning of the orientation dependence is unclear. In this study, we investigated the orientation dependence of susceptibility of human brain in vivo and mouse brains ex vivo. The source of susceptibility anisotropy in white matter is likely to be myelin as evidenced by the loss of anisotropy in the dysmyelinating shiverer mouse brain. A biophysical model is developed to investigate the effect of the molecular susceptibility anisotropy of myelin components, especially myelin lipids, on the bulk anisotropy observed by MRI. This model provides a consistent interpretation of the orientation dependence of macroscopic magnetic susceptibility in normal mouse brain ex vivo and human brain in vivo and the microscopic origin of anisotropic susceptibility. It is predicted by the theoretical model and illustrated by the experimental data that the magnetic susceptibility of the white matter is least diamagnetic along the fiber direction. This relationship allows an efficient extraction of fiber orientation using susceptibility tensor imaging. These results suggest that anisotropy on the molecular level can be observed on the macroscopic level when the molecules are aligned in a highly ordered manner. Similar to the utilization of magnetic susceptibility anisotropy in elucidating molecular structures, imaging magnetic susceptibility anisotropy may also provide a useful tool for elucidating the microstructure of ordered biological tissues. PMID- 22036682 TI - Apparent Fibre Density: a novel measure for the analysis of diffusion-weighted magnetic resonance images. AB - This article proposes a new measure called Apparent Fibre Density (AFD) for the analysis of high angular resolution diffusion-weighted images using higher-order information provided by fibre orientation distributions (FODs) computed using spherical deconvolution. AFD has the potential to provide specific information regarding differences between populations by identifying not only the location, but also the orientations along which differences exist. In this work, analytical and numerical Monte-Carlo simulations are used to support the use of the FOD amplitude as a quantitative measure (i.e. AFD) for population and longitudinal analysis. To perform robust voxel-based analysis of AFD, we present and evaluate a novel method to modulate the FOD to account for changes in fibre bundle cross sectional area that occur during spatial normalisation. We then describe a novel approach for statistical analysis of AFD that uses cluster-based inference of differences extended throughout space and orientation. Finally, we demonstrate the capability of the proposed method by performing voxel-based AFD comparisons between a group of Motor Neurone Disease patients and healthy control subjects. A significant decrease in AFD was detected along voxels and orientations corresponding to both the corticospinal tract and corpus callosal fibres that connect the primary motor cortices. In addition to corroborating previous findings in MND, this study demonstrates the clear advantage of using this type of analysis by identifying differences along single fibre bundles in regions containing multiple fibre populations. PMID- 22036683 TI - Validation of connectivity-based thalamic segmentation with direct electrophysiologic recordings from human sensory thalamus. AB - Connectivity-based segmentation has been used to identify functional gray matter subregions that are not discernable on conventional magnetic resonance imaging. However, the accuracy and reliability of this technique has only been validated using indirect means. In order to provide direct electrophysiologic validation of connectivity-based thalamic segmentations within human subjects, we assess the correlation of atlas-based thalamic anatomy, connectivity-based thalamic maps, and somatosensory evoked thalamic potentials in two adults with medication refractory epilepsy who were undergoing intracranial EEG monitoring with intrathalamic depth and subdural cortical strip electrodes. MRI with atlas derived localization was used to delineate the anatomic boundaries of the ventral posterolateral (VPL) nucleus of the thalamus. Somatosensory evoked potentials with intrathalamic electrodes physiologically identified a discrete region of phase reversal in the ventrolateral thalamus. Finally, DTI was obtained so that probabilistic tractography and connectivity-based segmentation could be performed to correlate the region of thalamus linked to sensory areas of the cortex, namely the postcentral gyrus. We independently utilized these three different methods in a blinded fashion to localize the "sensory" thalamus, demonstrating a high-degree of reproducible correlation between electrophysiologic and connectivity-based maps of the thalamus. This study provides direct electrophysiologic validation of probabilistic tractography-based thalamic segmentation. Importantly, this study provides an electrophysiological basis for using connectivity-based segmentation to further study subcortical anatomy and physiology while also providing the clinical basis for targeting deep brain nuclei with therapeutic stimulation. Finally, these direct recordings from human thalamus confirm early inferences of a sensory thalamic component of the N18 waveform in somatosensory evoked potentials. PMID- 22036684 TI - Cortical current source estimation from electroencephalography in combination with near-infrared spectroscopy as a hierarchical prior. AB - Previous simulation and experimental studies have demonstrated that the application of Variational Bayesian Multimodal EncephaloGraphy (VBMEG) to magnetoencephalography (MEG) data can be used to estimate cortical currents with high spatio-temporal resolution, by incorporating functional magnetic resonance imaging (fMRI) activity as a hierarchical prior. However, the use of combined MEG and fMRI is restricted by the high costs involved, a lack of portability and high sensitivity to body-motion artifacts. One possible solution for overcoming these limitations is to use a combination of electroencephalography (EEG) and near infrared spectroscopy (NIRS). This study therefore aimed to extend the possible applications of VBMEG to include EEG data with NIRS activity as a hierarchical prior. Using computer simulations and real experimental data, we evaluated the performance of VBMEG applied to EEG data under different conditions, including different numbers of EEG sensors and different prior information. The results suggest that VBMEG with NIRS prior performs well, even with as few as 19 EEG sensors. These findings indicate the potential value of clinically applying VBMEG using a combination of EEG and NIRS. PMID- 22036685 TI - Socio-economic and geographic differences in acceptability of community-based health insurance. PMID- 22036686 TI - Seasonality of medical contacts in school-aged children with asthma: association with school holidays. AB - OBJECTIVES: To assess the seasonality of medical contacts in children with asthma, to compare England with Scotland, and to assess the impact of medication compliance on the frequency of medical contacts. STUDY DESIGN: A retrospective study taken from the General Practice Research Database of daily medical contacts from 1999 to 2005 in a population of school-aged (5-16 years) children with a diagnosis of asthma, and age- and gender-matched controls. PRIMARY OUTCOME MEASURE: All unscheduled medical contacts. Prescription frequency for inhaled corticosteroids over the same period was also assessed. RESULTS: Data from 76,924 children were analyzed. There was an increase in unscheduled medical contacts for all children on return to school in September. Unscheduled medical contacts occurred almost twice as frequently in children with asthma compared with non asthmatic children. The frequency of medical contacts in children with asthma could be predicted from the frequency of medical contacts in non-asthmatic children. In the 3 months from September to December, unscheduled medical contacts were disproportionately greater than would be predicted for children with asthma relative to non-asthmatic children in both England and Scotland. The rise in medical contacts in Scotland preceded that in England by approximately 14 days, reflecting the earlier date for returning to school. The number of prescriptions for inhaled corticosteroids decreased in August. A higher incidence of unscheduled medical contacts was noted during September in those not receiving a prescription in August. CONCLUSIONS: Returning to school after the summer break is associated with a sharp increase in unscheduled medical contacts in school aged children, particularly in those with asthma. This follows a decrease in the number of prescriptions for inhaled corticosteroids. It is suggested that at least part of the excess numbers of unscheduled contacts in children with asthma is because they do not maintain their inhaled corticosteroids over the summer holidays. PMID- 22036687 TI - Deep brain stimulation of the pedunculopontine tegmental nucleus modulates neuronal hyperactivity and enhanced beta oscillatory activity of the subthalamic nucleus in the rat 6-hydroxydopamine model. AB - Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) area has been introduced as a novel surgical therapy for dopamine refractory gait problems, freezing and postural instability in the late stage of Parkinson's disease (PD). Lesions of the pedunculopontine tegmental (PPTg) nucleus, the equivalent of the PPN in rodents, were shown to reduce the elevated discharge rate of the subthalamic nucleus (STN) in the 6-hydroxydopamine (6-OHDA) rat model of PD. In order to further elucidate the modulatory effect of the PPTg on the STN we examined the effect of 25 Hz low frequency PPTg stimulation on neuronal single unit activity and oscillatory local field potentials (LFPs) of the STN, and on the electrocorticogram (ECoG) of the primary motor cortex region in rats with unilateral 6-OHDA induced nigrostriatal lesions. Stimulation of the PPTg reduced the enhanced firing rate in the STN, without affecting the firing pattern or approximate entropy (ApEn). It also reduced the activity in the beta band (15-30 Hz) of the STN, which is elevated in 6-OHDA lesioned rats, without affecting beta activity in the motor cortex. We showed a modulatory effect of PPTg stimulation on altered neuronal STN activity in the PD 6-OHDA rat model, indicating that PPTg DBS may alter activity of the basal ganglia circuitry at least partially. It remains unclear, however, how these changes are exactly mediated and whether they are relevant with regard to the descending PPTg projections in the lower brainstem. PMID- 22036688 TI - Do we still need to develop new imaging biomarkers of dopamine denervation for Parkinson's disease? PMID- 22036690 TI - Culturing explanted colon crypts highly improves viability of primary non transformed human colon epithelial cells. AB - Chemoprotective effects of nutritional compounds are usually studied in cell lines. Studies using primary human colon cells have been limited due to the lack of established methods regarding their culture. We therefore optimized isolation and culture of non-transformed human epithelial cells from individual donors to enrich viable cells and sufficient amounts of intact RNA. Isolated epithelial cells were seeded in different coated cell culture dishes combined with several media (2-24h). To avoid cells from anoikis, also intact colon crypts were isolated to maintain cell interactions. These crypts were incubated with gut fermentation products (24h) derived from indigestible carbohydrates. In none of the coated (fibronectin, laminin) cell culture dishes isolated epithelial cells did attach. The number of these cells remaining in suspension, decreased already after 2h to 20%. Intact colon crypts cultured as pellets showed a stable viability up to 24h (91+/-4%) and were suitable to gain a sufficient quantity of RNA. The use of colon crypts with an appropriate cell culture medium could double the lifespan of intestinal epithelial cells from 12 up to 24h and represents a promising approach to study early events in carcinogenesis and chemoprevention as well as other diseases of the colon. PMID- 22036692 TI - Intracerebral recordings of the Bereitschaftspotential demonstrate the heterogeneity of its components. AB - Though consisting of early and late components, the evoked potential preceding a voluntary movement (Bereitschaftspotential - BP) is often considered as a unitary phenomenon. By analyzing intracerebrally recorded BP we attempted to demonstrate that the components are electrophysiological correlates of separate operations. The BPs recorded in 42 epilepsy surgery candidates (28 men, 14 women; aged from 18 to 49 years) during self-paced clenching movements of the hand opposite to the explored hemisphere were investigated in the study. Microdeep intracerebral 5 to 15-contact electrodes were used. The averaged curves were calculated from approximately 30 trials in each case. All the records were taken with a binaural reference. The total number of explored brain regions was 235; the event-related premovement potentials were observed in 121 of them. Three types of premovement responses were observed: (i) the BP with both components; (ii) the BP with the early component only; and (iii) the BP with the late component only. The generators of the early one-component BP were demonstrated in two frontal cortical areas (precentral and middle frontal gyri) and in the parietal area known to be involved in action planning and decision making (precuneus). Some structures generating the early one-component BP were activated during movement; the others were without motor responsiveness. The results suggest a separate elaboration of functional task items in some and their integration in other brain structures, and the existence of volitional mechanisms of different hierarchical character. PMID- 22036689 TI - Corneal endothelial autocrine trophic factor VIP in a mechanism-based strategy to enhance human donor cornea preservation for transplantation. AB - Vasoactive intestinal peptide (VIP) and ciliary neurotrophic factor (CNTF) are identified as autocrines of human corneal endothelial (CE) cells working in concert to maintain the differentiated state and promote the survival of the corneal endothelium. From VIP gene knockdown study, endogenous VIP is shown to maintain the level of the differentiation marker, the adhesion molecule N cadherin, CE cell size, shape, and retention, in situ in the human donor corneoscleral explants. Exogenous VIP protects the corneal endothelium against the killing effect of oxidative stress, in part by upholding ATP levels in CE cells dying of oxidative stress-induced injury, allowing them to die of an apoptotic death instead of an acute necrotic one. The switch from the acute necrosis to the programmed cell death (apoptosis) may have allowed the injured CE cell to be rescued by the VIP-upregulated pathways, including those of Bcl-2 and N-cadherin, and resulted in long-term CE cell survival. The endogenous VIP in CE cells is upregulated by CNTF, which is released by CE cells surviving the oxidative stress. The CNTF receptor (CNTFRalpha) is expressed in CE cells in human donor corneoscleral explant and gradually becomes lost during corneal storage. VIP treatment (10(-8) M, 37 degrees C, 30 min) prior to storage of freshly dissected human donor corneoscleral explants increases their CE cell CNTFRalpha level and responsiveness to CNTF in upregulating the gap junctional protein connexin-43 expression. VIP treatment of both fresh and preserved corneoscleral explants reduces CE damage in the corneoscleral explants and in the corneal buttons trephined from them. CE cell loss is a critical risk factor in corneal graft failure at any time in the life of the graft, which can be as late as 5-10 years after an initially successful transplant. A new procedure, Descemet's stripping automated endothelial keratoplasty (DSAEK), which is superior to the traditional full thickness transplantation in many aspects, nevertheless subjects the corneal endothelium to extensive mechanical forces, resulting in even more pronounced CE cell loss than the traditional technique. Whereas it is known that cells transduce mechanical stress through N-cadherin, stimulation of the N-cadherin pathway increases the anti-apoptotic protein Bcl-2 expression. Since N-cadherin and Bcl-2 in the corneal endothelium are both upregulated by VIP, we aim to strengthen the CE sheet by VIP treatments of the corneoscleral explants for full thickness traditional corneal transplantation and pre-cut corneas for DSAEK. PMID- 22036693 TI - Eye movement evidence for defocused attention in dysphoria--a perceptual span analysis. AB - The defocused attention hypothesis (von Hecker and Meiser, 2005) assumes that negative mood broadens attention, whereas the analytical rumination hypothesis (Andrews and Thompson, 2009) suggests a narrowing of the attentional focus with depression. We tested these conflicting hypotheses by directly measuring the perceptual span in groups of dysphoric and control subjects, using eye tracking. In the moving window paradigm, information outside of a variable-width gaze contingent window was masked during reading of sentences. In measures of sentence reading time and mean fixation duration, dysphoric subjects were more pronouncedly affected than controls by a reduced window size. This difference supports the defocused attention hypothesis and seems hard to reconcile with a narrowing of attentional focus. PMID- 22036694 TI - Aneurysm diameter measurement: a challenging and frustrating task. PMID- 22036695 TI - Data surveillance in child protection systems development: an Indonesian case study. AB - OBJECTIVES: Successful implementation of child protection program interventions and child and family welfare services is contingent upon the availability and use of good quality information, as emphasized by the recent Convention on the Rights of the Child's General Comment 13. Yet, the role of information within child protection is not well understood, and ongoing efforts to strengthen child protection systems have not systematically examined this critical function. Recognizing these shortcomings, the Government of Indonesia and UNICEF commissioned a study to identify a "road map" for a national child protection information system. METHODS: The used desk review, semi-structured interviews, focus groups and site visits to identify existing data collection practices, and analyze the appropriateness and efficiency of information management mechanisms from the national down to the community level. RESULTS: The results show that the prevailing situation in Indonesia is characterized by a lack of accurate information on all necessary aspects of child care and protection including magnitude of problems, causality analysis and impact of programmatic responses. There is no lead actor for child protection at the national level, and there are no agreed upon data collection priorities, procedures or methods for a shared data collection system. CONCLUSION: The study suggests a need to reframe the dominant language from a "child protection information management system" to a "child protection surveillance system" to promote clearer data collection objectives and activities. Identifying a government ministry to lead child protection efforts and to forge closer partnerships among relevant actors will be required to support a national surveillance system. Additionally, addressing obstacles that limit child protection incident detection at the community level is critical. In addition to strengthening Indonesia's system, this study's approach and findings have the potential to help to inform ongoing child protection system development initiatives in other countries as well. PMID- 22036696 TI - Using LOINC to link 10 terminology standards to one unified standard in a specialized domain. AB - Despite the existence of multiple standards for the coding of biomedical data and the known benefits of doing so, there remain a myriad of biomedical information domain spaces that are essentially un-coded and unstandardized. Perhaps a worse situation is when the same or similar information in a given domain is coded to a variety of different standards. Such is the case with cephalometrics - standardized measurements of angles and distances between specified landmarks on X-ray film used for orthodontic treatment planning and a variety of research applications. We describe how we unified the existing cephalometric definitions from 10 existing cephalometric standards to one unifying terminology set using an existing standard (LOINC). Using our example of an open and web-based orthodontic case file system, we describe how this work benefited our project and discuss how adopting or expanding established standards can benefit other similar projects in specialized domains. PMID- 22036697 TI - A preliminary study of the effects of individual patient-level feedback in outpatient substance abuse treatment programs. AB - The purpose of this study was to examine the effects of feedback provided to counselors on the outcomes of patients treated at community-based substance abuse treatment programs. A version of the Outcome Questionnaire (OQ-45), adapted to include drug and alcohol use, was administered to patients (N = 304) in 3 substance abuse treatment clinics. Phase I of the study consisted only of administration of the assessment instruments. Phase II consisted of providing feedback reports to counselors based on the adapted OQ-45 at every treatment session up to Session 12. Patients who were found to not be progressing at an expectable rate (i.e., "offtrack") were administered a questionnaire that was used as a second feedback report for counselors. For offtrack patients, feedback compared with no feedback led to significant linear reductions in alcohol use throughout treatment and also in OQ-45 total scores and drug use from the point of the second feedback instrument to Session 12. The effect for improving mental health functioning was evident at only 1 of the 3 clinics. These results suggest that a feedback system adapted to the treatment of substance use problems is a promising approach that should be tested in a larger randomized trial. PMID- 22036698 TI - Longitudinal changes in hippocampal volumes and cognition in remitted geriatric depressive disorder. AB - Growing evidences suggest that the abnormality of hippocampal volume may occur in the process of depression. In this longitudinal study, we calculated the hippocampal volume of 14 remitted geriatric depressed (RGD) patients and 19 healthy participants at baseline and follow-up. We found significant improvement of performance in Trail Making Test-A (P=0.038) and Test-B (P=0.032), and the right hippocampal volume increased mildly in RGD. However, in RGD patients, positive correlations were seen between the changes in right hippocampal volumes and Symbol Digit Modality Test scores (r=0.675, P=0.008), and changes in left hippocampal volumes and Mini-Mental State Examination scores (r=0.743, P=0.002). Our findings suggest that hippocampus related cognitive impairment and previously addressed decreased hippocampal volume might represent a state rather than a permanent trait of the depressive disorder. The results suggest that hippocampal volume may be a useful risk marker for conversion to Alzheimer's disease in RGD patients. Additionally, our study indicates that effective antidepressants treatment might postpone and even revise the deterioration of hippocampus to some degree. PMID- 22036699 TI - The effects of gonadectomy on sex- and age-typical responses to novelty and ethanol-induced social inhibition in adult male and female Sprague-Dawley rats. AB - Sex- and age-typical responses to ethanol and novel stimuli tend to emerge postpubertally, suggesting a potential organizational or activational role for pubertal hormones in these behaviors. To test this possibility, male and female rats were gonadectomized (GX) or received sham gonadectomy (SH) either prepubertally on postnatal day (P) 23 (early) or in adulthood on P70 (late). Animals were tested as adults for response to novelty and, on the following day, challenged with either saline or ethanol (1g/kg) prior to social interaction testing with an unfamiliar partner in a familiar setting under low light conditions. Gonadectomy did not influence ethanol-induced social inhibition in either sex, but instead altered the microstructure of social behavior, with GX animals exhibiting proportionally less time in social investigation and proportionally more time in contact behavior than SH animals, regardless of age of gonadectomy. The early sham surgical manipulation process itself influenced social motivation, with early SH surgery eliminating ethanol-induced decreases in social preference in both sexes. Response to novelty was unaffected by gonadectomy, but was suppressed in early compared to late SH manipulated animals. These results suggest that adult-typical responses to ethanol and novelty directed behaviors are little influenced by gonadal hormones during puberty or in adulthood. However, the experience of surgical manipulation itself during development exerts behavioral and pharmacological consequences that last into adulthood. PMID- 22036700 TI - Social and cognitive processes influencing grammar evolution. Comment on 'Modelling the cultural evolution of language' by Luc Steels. PMID- 22036701 TI - An ecological account of language evolution! Way to go! Commentary on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22036702 TI - Language origin from simulation of language evolution. Comment on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22036703 TI - In Silico Linguistics. Comment on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22036704 TI - Are phylogenetic position, virulence, drug susceptibility and in vivo response to treatment in mycobacteria interrelated? AB - Phylogenetic analyses on the basis of multiple house-keeping genes and whole genome sequences have offered new insights in the phylogeny of the genus Mycobacterium. This genus yields obligate pathogens, the M. tuberculosis complex and M. leprae, as well as opportunistic pathogens (e.g. M. avium, M. intracellulare, M. kansasii, M. marinum, M. malmoense) and saprophytes (e.g. M. phlei, M. sphagni, M. gordonae). The most virulent mycobacteria, the M. tuberculosis complex, M. leprae and the M. kansasii-M. szulgai-M. marinum-M. ulcerans group are phylogenetically related and infections by these organisms are better treatable than those caused by less virulent and phylogenetically more distantly related Mycobacterium species. The most virulent Mycobacterium species are also characterized by high levels of natural drug susceptibility. In this paper, we review studies of phylogeny, drug susceptibility, and clinical significance to support our hypothesis that drug susceptibility in mycobacteria is acquired and reflects the low level of competition in -and adaptation to- a closer-to-human (environmental) niche. In turn, mycobacteria that inhabit the most competitive environmental niches are the least adapted to humans, thus of low clinical significance, but most tolerant to antibiotics derived from microbes with which they share their habitat, lowering the chances of cure in case of infection. PMID- 22036705 TI - Contrasting patterns of population genetic structure of Fasciola hepatica from cattle and sheep: implications for the evolution of anthelmintic resistance. AB - Twelve polymorphic genetic markers, eight allozymic loci and four microsatellites, were used to characterize 20 infrapopulations of Fasciola hepatica (all flukes from 10 individual cattle and 10 sheep) from 11 farms in Northwest Spain. Results suggest different patterns of population genetic structure depending on the host species. Individuals identified as clones were much more frequent in sheep. The common presence of clones and its nonrandom occurrence among individual hosts suggests clumped transmission of liver flukes in sheep. After reducing significant repeated multilocus genotypes to one unique copy within infrapopulations, results show relatively high levels of gene diversity within infrapopulations from cattle and sheep (0.411 and 0.360 on average, respectively). However, parasites of sheep appear to show significantly more structured variation at the infrapopulation level (Standardized F(ST)=0.087 and 0.170 for parasites of cattle and sheep, respectively). Compared to the parasites from cattle, results suggest that populations from sheep show lower levels of gene flow, higher degree of aggregate transmission, higher probability of mating within clones, and lower parasitic load. These differences have implications for the evolution of anthelmintic resistance because they affect the effective population size and the degree of inbreeding. The development and rapid spread of resistance seems likely in the parasites of cattle because populations from the study area are characterized by high gene flow. However, results also suggest that the efficient selection of a new recessive advantageous mutation would be favored in parasites of sheep due to a greater potential for inbreeding. PMID- 22036706 TI - The quiet and controversial: Ural family of Mycobacterium tuberculosis. AB - The absence of lateral gene exchange is a characteristic feature defining the genome evolution and clonal population structure of Mycobacterium tuberculosis. Certain of its lineages have justly attracted more attention due to their global dissemination and/or remarkable pathogenic properties. In this critical review, I discuss the population structure and genetic geography of the less 'popular' but in some aspects no less noteworthy M. tuberculosis lineage, Ural family. Its specific signature was initially defined by single copy in MIRU26, and large (>6) copy number in MIRU10 loci, and by 43-spoligotyping as absence of signals 29-31 and 33-36. Here, I suggest to subdivide Ural strains with present and absent spoligosignal 2 into primary Ural-1 and secondary Ural-2 sublineages, respectively, while 1 copy in MIRU26 is specific of Ural-1. Furthermore, three copies were recently described in MIRU10 in Ural-1 strains which highlights a high diversity of this locus in Ural genotype. The data on the two Ural sublineages were extracted from SpolDB4 database and original publications in order to trace their distribution at global and within-country levels. Importantly, the rigorous reanalysis suggested the true rate of the Ural genotype in the Ural area in Russia to be only 7%. In contrast, the frequencies of the Ural sublineages peak elsewhere: in South Ukraine and Georgia/Abkhazia (Ural-1, up to 14-19%), and in southwestern Iran (Ural-2, up to 26%). However, as this name is used since 2005, it seems most parsimonious to continue its use even if misleading. The forest graph was built on the available spoligoprofiles of Ural family strains from Eurasia. It helped to suggest routes of their primary dispersal that are discussed in the context of the known human migrations also influenced by natural barriers. The north/east Pontic area may have been an area of origin and primary dispersal of the Ural (Ural-1) genotype in Eurasia, whereas political and natural borders may have influenced its subsequent dissemination throughout Central Asia. Studies of phenotypic properties in different models, comparison with host genetics give evidence that the Ural family strains are not associated with increased capacity to acquire drug resistance, pathogenicity or transmissibility. Instead since Ural family is rather moderately widespread in Eurasia beyond the hypothesized areas of origin, this situation may be a result of its low contagiosity as a consequence of long-term co-adaptation with human host. Future research should be focused on whole-genome sequencing in order to identify Ural-specific SNP and/or deletion, to resolve its phylogenetic and phylogeographic uncertainty and to elucidate biological features underlying its circulation and co-evolution with the human species. PMID- 22036707 TI - Dengue virus surveillance in Singapore reveals high viral diversity through multiple introductions and in situ evolution. AB - Dengue fever, a vector-borne disease, has caused tremendous burden to countries in the tropics and sub tropics. Over the past 20 years, dengue epidemics have become more widespread, severe and frequent. This study aims to understand the dynamics of dengue viruses in cosmopolitan Singapore. Envelope protein gene sequences of all four dengue serotypes (DENV-1-DENV-4) obtained from human sera in Singapore (2008-2010) revealed that constant viral introductions and in situ evolution contribute to viral diversity in Singapore and play important roles in shaping the epidemiology of dengue in the island state. The diversity of dengue viruses reported here could be a reflection of the on-going dengue situation in the region given Singapore's location in a dengue hyperendemic region and its role as the regional hub for travels and trade. Though cosmopolitan genotype of DENV-2 has remained as the predominant strain circulating in Singapore, we uncovered evidence of in situ evolution which could possibly result in viruses with improved fitness. While we have previously shown that a switch in the predominant dengue serotype could serve as a warning for an impending outbreak, our current data shows that a replacement of a predominant viral clade, even in the absence of a switch in predominant serotype, could signal a possible increase in dengue transmission. The circulating dengue viruses in Singapore are highly diverse, a situation which could offer ample opportunities for selection of strains of higher fitness, thus increasing the risk of outbreaks despite a low Aedes population. PMID- 22036708 TI - Government uses new method to judge performance of hospitals to try to prevent "gaming" of system. PMID- 22036709 TI - Liberal Democrats end their opposition to health reforms. PMID- 22036710 TI - Challenges ahead in signal transduction: MAPK as an example. AB - Signal transduction is the process of converting one kind of signal or stimulus into another, with the goal of processing external or internal signals into diverse functions. In recent years, progress has been made in identifying signaling pathways, investigating cross-talk and feedbacks in signaling modules, analyzing cell-type specific signaling, and unraveling spatial-temporal aspects, such as receptor clustering into micro-domains, dynamic localization, and mathematical modeling. Here, we used the receptor/MAPK signaling system as an example, and we discuss the current and remaining challenges: the role of scaffolds and signaling machines, the importance of concentration and competition, the use of structural information, the integration of large-scale proteomic datasets, and the future challenge of integrating alternative splicing into signaling pathways. PMID- 22036711 TI - Maximizing reductant flow into microbial H2 production. AB - Developing microbes into a sustainable source of hydrogen gas (H2) will require maximizing intracellular reductant flow toward the H2-producing enzymes. Recent attempts to increase H2 production in dark fermentative bacteria include increasing oxidation of organic substrates through metabolic engineering and expression of exogenous hydrogenases. In photofermentative bacteria, H2 production can be increased by minimizing reductant flow into competing pathways such as biomass formation and the Calvin cycle. One method of directing reductant toward H2 production being investigated in oxygenic phototrophs, which could potentially be applied to other H2-producing organisms, is the tethering of electron donors and acceptors, such as hydrogenase and photosystem I, to create new intermolecular electron transfer pathways. PMID- 22036712 TI - Identification and characterization of novel splice variants of the human EPM2A gene mutated in Lafora progressive myoclonus epilepsy. AB - The EPM2A gene, defective in the fatal neurodegenerative disorder Lafora disease (LD), is known to encode two distinct proteins by differential splicing; a phosphatase active cytoplasmic isoform and a phosphatase inactive nuclear isoform. We report here the identification of three novel EPM2A splice variants with potential to code for five distinct proteins in alternate reading frames. These novel isoforms, when ectopically expressed in cell lines, show distinct subcellular localization, interact with and serve as substrates of malin ubiquitin ligase-the second protein defective in LD. Two phosphatase active isoforms interact to form a heterodimeric complex that is inactive as a phosphatase in vitro, suggesting an antagonistic function for laforin isoforms if expressed endogenously in significant amounts in human tissues. Thus alternative splicing could possibly be one of the mechanisms by which EPM2A may regulate the cellular functions of the proteins it codes for. PMID- 22036713 TI - Options for procedural pain in newborn infants. PMID- 22036714 TI - Management of sexually transmitted infections in pubertal children. AB - Sexually transmitted infections (STI) comprise a variety of infections transmissible through sexual contact. Mutually consenting sexual relationships have become commonplace in adolescence and sexual abuse or exploitation awareness has risen, resulting in increased presentations of children with sexual health concerns. Difficulties persist in diagnosing and managing STIs in children. With increased emphasis on paediatrician's involvement in transitional care, competence in sexual history taking and clinical presentation recognition remains essential. Additionally, an awareness of strengths and limitations of diagnostic modalities needs to be present. Furthermore, specific additional issues in this age group such as independent consent for diagnosis and treatment, fear of pregnancy and privacy and confidentiality concerns should be addressed carefully. Failure to address these issues may lead to disengagement with health services resulting in potentially adverse short- and long-term health and social consequences in young persons. This review aims to provide an overview of an approach to diagnosing and managing a pubertal child with an STI and the consideration of the unique issues surrounding children's care. PMID- 22036715 TI - Successful use of factor VIIa to control life-threatening post-operative haemorrhage in a patient on extra-corporeal membrane oxygenation. AB - Recombinant Factor VII (Novoseven) is gaining recognition as an established treatment option for post-cardiac surgery bleeding. However, little information is available on its use in patients being maintained on Extra-Corporeal Membrane Oxygenation (ECMO) support, particularly in the adult population. We present the first case of the successful use of Factor VIIa to control bleeding in an adult patient on ECMO post cardiac surgery. PMID- 22036716 TI - Patient acceptance and attitude toward an alternative method of subconjunctival injection for the medical treatment of glaucoma. AB - PURPOSE: Nonadherence to glaucoma medications may be a major cause of treatment failure. We examined the acceptance of glaucoma patients toward a possible new route of administering glaucoma medication by subconjunctival injection. PATIENTS AND METHODS: Patients were recruited from specialist glaucoma clinics on a voluntary basis. Trained interviewers administered a 30-item questionnaire and an information sheet with details of an alternative subconjunctival injection route involving injections at 3-month intervals. Outcome measures regarding acceptance of the new procedure, social situational factors, disease factors, and treatment factors were assessed. RESULTS: A total of 151 patients participated in this study. Of the 151 patients 112 (74.2%) were willing to have their glaucoma medication given by the new method of subconjunctival injection, 101 of 112 (90.2%) were willing to accept it at the same cost as their present medication, and 87 of 101 (86.1%) were willing to accept it even at a higher cost. These patients tended to be on a greater number of medications (P=0.006), and medicating more frequently in a day (P=0.003). Nine of 10 (90%) patients who were admitted to nonadherence were willing to accept subconjunctival injections at 3 month intervals in place of their topical medication. CONCLUSIONS: Our study found that 74% of glaucoma patients were willing to accept an alternative form of glaucoma treatment through 3-monthly subconjunctival injections. A large proportion of patients who were admitted to nonadherence to topical medication were willing to consider this alternative method of medication. Our findings are helpful when developing patient-acceptable drug-delivery regimes, which may alleviate the need for daily medication. PMID- 22036717 TI - Crystal structure of the EphA4 protein tyrosine kinase domain in the apo- and dasatinib-bound state. AB - The Eph family of receptor tyrosine kinases regulates diverse cellular processes while the over-expression of a member of this family, EphA4, has been reported in a variety of malignant carcinomas. To gain insight into molecular mechanisms and to facilitate structure-based inhibitor design, we solved the crystal structure of the native EphA4 kinase domain in both the apo and dasatinib bound forms. Analysis of the two structures provides insight into structural features of inhibitor binding and revealed a hydrophobic back-pocket in the ATP- binding site of EphA4 which was previously unidentified. The structures suggest a route towards development of novel and specific inhibitors. PMID- 22036718 TI - MicroRNA 506 regulates expression of PPAR alpha in hydroxycamptothecin-resistant human colon cancer cells. AB - Chemotherapeutic drug resistance remains a major obstacle to the successful treatment of colon cancer. Here, we show that 77 differentially expressed miRNAs were identified in SW1116/HCPT versus SW1116, and over-expressed miR-506 in SW1116/HCPT cells was validated. Then it was indicated that PPARalpha is a common target of miR-506 by using a luciferase reporter assay. Our results also demonstrated that cytotoxic ability of HCPT requires the concomitant presence of PPARalpha, and that loss of PPARalpha expression imparts resistance to HCPTs anti tumor effects. All together, our studies indicate that miR-506 over-expression in established HCPT-resistant colon cancer cell line confers resistance to HCPT by inhibiting PPARalpha expression, then providing a rationale for the development of miRNA-based strategies for reversing resistance in HCPT-resistant colon cancer cells. PMID- 22036719 TI - Differences in regional myocardial perfusion, metabolism, MVO2, and edema after coronary sinus machine perfusion preservation of canine hearts. AB - Machine perfusion improves solid organ preservation for transplantation. We have demonstrated that antegrade perfusion preservation of hearts is superior to cold storage but may be limited by aortic valve incompetence. We hypothesized that retrograde perfusion (RP) through the coronary sinus may provide more reliable perfusate delivery to the heart. This study was designed to determine the optimal perfusion parameters and evaluate regional flow after RP of canine hearts. After donor cardiectomy, canine hearts (n = 6) were established in a perfusion device (LifeCradle, Organ Transport Systems, Inc., Frisco, TX) through a coronary sinus catheter. Hearts were perfused at 5 degrees C over flow rates from 10 to 35 ml/100 g myocardium/min for 20 minutes at each flow rate. Colored microspheres were used to quantify tissue perfusion. Oxygen consumption (MVO(2)) and perfusion parameters were measured. At end-perfusion, tissue was collected for proton magnetic resonance spectroscopy ((1)H MRS), microsphere analysis, and determination of myocardial edema. MVO(2) increased up to flow rates of 20 ml/100 g/min. Right ventricular (RV) perfusion was reduced at all flow rates. Increased lactate/alanine ratios by (1)H MRS and reduced myocardial water content were noted in RV samples. RP results in excellent left ventricular (LV) perfusion. RV perfusion is reduced and oxidative metabolism in the right ventricle may not be maintained by RP. Further studies to evaluate effects of reduced RV perfusion by RP on functional recovery after transplantation are warranted. PMID- 22036720 TI - Coronary artery bypass grafting in patients with type 2 diabetes mellitus: a comparison between minimized and conventional extracorporeal circulation. AB - Diabetes mellitus (DM) is an established independent risk factor for significant morbidity and mortality after coronary artery bypass grafting (CABG). The minimized extracorporeal circulation (MECC) allows a reduction of the negative effects associated with conventional extracorporeal circulation (CECC). In this study, the impact of the MECC on outcome of diabetic patients after CABG was assessed. Between January 2002 and December 2009, 1,184 patients with DM underwent elective isolated CABG using CECC (54.6%) or MECC (45.4%). All analysis was performed retrospectively. The extracorporeal circulation time was significantly reduced during MECC procedure. The postoperative increase of creatine kinase and lactate levels was significantly weaker in the MECC group (p < 0.001). Also, the transfusion requirements were significantly lower (p < 0.001). Furthermore, MECC patients had lower incidences of postoperative acute renal failure and sternal wound infections and shorter ICU and hospital lengths of stay (p < 0.05). Moreover, 30-day mortality was significantly reduced in the MECC group (p < 0.05). In conclusion, CABG surgery using MECC system is a safe alternative in patients with DM. A reduced postoperative mortality and lengths of stay, lower transfusion requirements, less renal and myocardial damage, and lower incidence of sternal wound infections encourage the usage of MECC system, especially in high-risk patients. PMID- 22036721 TI - Use of a miniaturized cardiopulmonary bypass circuit in neonates and infants is associated with fewer blood product transfusions. AB - Miniaturized bypass circuits, including the Kids D100 oxygenator and the D130 arterial filter, were specially designed to reduce blood transfusions in small infants undergoing cardiac surgery. This study compared the number of blood product transfusions and short-term outcome between patients younger than 1 year undergoing cardiac surgery with a conventional and a miniaturized bypass circuit, after controlling for baseline characteristics and surgical complexity by 1:1 matching. Adjusted odds ratios (ORs) and 95% confidence intervals for exposure to transfusions and to any additional transfusion were estimated from binary and polytomous regression models. Of the 804 patients enrolled retrospectively, 246 were analyzed after matching. The use of the miniaturized circuit required a lower priming volume, 265.5 vs. 432.4 mL, p < 0.001, fewer packed red blood cell (PRBC) transfusions, 1.4 vs. 2.0 U, p < 0.001, and fewer platelet transfusions on the day of surgery, 57.7% vs. 76.4%, p < 0.001. After adjustment for the use of antifibrinolytics, the ultrafiltration rate, and the year of surgery, the use of the miniaturized circuit was independently related to a reduced risk of additional PRBC transfusions, OR 0.04 (0.01, 0.13), and exposure to platelet transfusions, OR 0.78 (0.63, 0.96). Short-term outcome was similar. PMID- 22036722 TI - Influence of vascular network design on gas transfer in lung assist device technology. AB - Blood oxygenators are vital for the critically ill, but their use is limited to the hospital setting. A portable blood oxygenator or a lung assist device for ambulatory or long-term use would greatly benefit patients with chronic lung disease. In this work, a biomimetic blood oxygenator system was developed which consisted of a microfluidic vascular network covered by a gas permeable silicone membrane. This system was used to determine the influence of key microfluidic parameters-channel size, oxygen exposure length, and blood shear rate-on blood oxygenation and carbon dioxide removal. Total gas transfer increased linearly with flow rate, independent of channel size and oxygen exposure length. On average, CO(2) transfer was 4.3 times higher than oxygen transfer. Blood oxygen saturation was also found to depend on the flow rate per channel but in an inverse manner; oxygenation decreased and approached an asymptote as the flow rate per channel increased. These relationships can be used to optimize future biomimetic vascular networks for specific lung applications: gas transfer for carbon dioxide removal in patients with chronic obstructive pulmonary disease or oxygenation for premature infants requiring complete lung replacement therapy. PMID- 22036723 TI - Nitric oxide-generating silicone as a blood-contacting biomaterial. AB - Coagulation upon blood-contacting biomaterials remains a problem for short- and long-term clinical applications. This study examined the ability of copper(II) doped silicone surfaces to generate nitric oxide (NO) and locally inhibit coagulation. Silicone was doped with 3-MUm copper [Cu(0)] particles yielding 3 to 10 weight percent (wt%) Cu in 70-MUm thick Cu/silicone polymeric matrix composites (Cu/Si PMCs). At 3, 5, 8, and 10 wt% Cu doping, the surface expression of Cu was 12.1% +/- 2.8%, 19.7% +/- 5.4%, 29.0% +/- 3.8%, and 33.8% +/- 6.5%, respectively. After oxidizing Cu(0) to Cu(II) by spontaneous corrosion, NO flux, J(NO) (mol . cm(-2) . min(-1)), as measured by chemiluminescence, increased with surface Cu expression according to the relationship J(NO) = (1.63%SA(Cu) - 0.81) * 10(-11), R(2) = 0.98, where %SA(Cu) is the percentage of surface occupied by Cu. NO flux at 10 wt% Cu was 5.35 +/- 0.74 * 10(-10) mol . cm(-2) . min(-1). The clotting time of sheep blood exposed to these surfaces was 80 +/- 13 seconds with pure silicone and 339 +/- 44 seconds when 10 wt% Cu(II) was added. Scanning electron microscopies (SEMs) of coatings showed clots occurred away from exposed Cu dendrites. In conclusion, Cu/Si PMCs inhibit coagulation in a dose-dependent fashion related to the extent of copper exposure on the coated surface. PMID- 22036724 TI - Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation. AB - Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE(2) production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE(2) in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-kappaB signaling showed that LAME inhibits the phosphorylation of IkappaBalpha and IkappaBbeta, preventing their degradation and the nuclear translocation of the NF-kappaB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor beta (TGF-beta)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-alpha and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-alpha). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. PMID- 22036725 TI - Sulfur mustard primes human neutrophils for increased degranulation and stimulates cytokine release via TRPM2/p38 MAPK signaling. AB - Sulfur mustard (2,2'-bis-chloroethyl-sulfide; SM) has been a military threat since the World War I. The emerging threat of bioterrorism makes SM a major threat not only to military but also to civilian world. SM injury elicits an inflammatory response characterized by infiltration of neutrophils. Although SM was reported to prime neutrophils, the mechanism has not been identified yet. In the present study, we investigated the mechanism of SM-induced priming in human neutrophils. SM increased [Ca(2+)](i) in human neutrophils in a concentration dependent fashion. Transient receptor potential melastatin (TRPM) 2 inhibitors (clotrimazole, econazole and flufenamic acid) and silencing of TRPM2 by shRNA attenuated SM-induced [Ca(2+)](i) increase. SM primed degranulation of azurophil and specific granules in response to activation by fMLP as previously reported. SB203580, an inhibitor of p38 MAPK, inhibited SM-induced priming. Neither PD98057, an ERK inhibitor, nor SP600215, a JNK inhibitor, inhibited SM-induced priming. In addition, SM enhanced phosphorylation of NF-kB p65 and release of TNF alpha, interleukin (IL)-6 and IL-8. SB203580 inhibited SM-induced NF-kB phosphorylation and cytokine release. These results suggest the involvement of TRPM2/p38 MAPK pathway in SM-induced priming and cytokines release in neutrophils. PMID- 22036726 TI - Antibacterial agent triclosan suppresses RBL-2H3 mast cell function. AB - Triclosan is a broad-spectrum antibacterial agent, which has been shown previously to alleviate human allergic skin disease. The purpose of this study was to investigate the hypothesis that the mechanism of this action of triclosan is, in part, due to effects on mast cell function. Mast cells play important roles in allergy, asthma, parasite defense, and carcinogenesis. In response to various stimuli, mast cells degranulate, releasing allergic mediators such as histamine. In order to investigate the potential anti-inflammatory effect of triclosan on mast cells, we monitored the level of degranulation in a mast cell model, rat basophilic leukemia cells, clone 2H3. Having functional homology to human mast cells, as well as a very well defined signaling pathway leading to degranulation, this cell line has been widely used to gain insight into mast-cell driven allergic disorders in humans. Using a fluorescent microplate assay, we determined that triclosan strongly dampened the release of granules from activated rat mast cells starting at 2 MUM treatment, with dose-responsive suppression through 30 MUM. These concentrations were found to be non-cytotoxic. The inhibition was found to persist when early signaling events (such as IgE receptor aggregation and tyrosine phosphorylation) were bypassed by using calcium ionophore stimulation, indicating that the target for triclosan in this pathway is likely downstream of the calcium signaling event. Triclosan also strongly suppressed F-actin remodeling and cell membrane ruffling, a physiological process that accompanies degranulation. Our finding that triclosan inhibits mast cell function may explain the clinical data mentioned above and supports the use of triclosan or a mechanistically similar compound as a topical treatment for allergic skin disease, such as eczema. PMID- 22036727 TI - Role of the Nrf2-heme oxygenase-1 pathway in silver nanoparticle-mediated cytotoxicity. AB - Silver nanoparticles (nano-Ag) have been widely used in various commercial products including textiles, electronic appliances and biomedical products. However, there remains insufficient information on the potential risk of nano-Ag to human health and environment. In the current study, we have investigated the role of NF-E2-related factor 2 (Nrf2) transcription factor in nano-Ag-induced cytotoxicity. When Nrf2 expression was blocked using interring RNA expression in ovarian carcinoma cell line, nano-Ag treatment showed a substantial decrease in cell viability with concomitant increases in apoptosis and DNA damage compared to the control cells. Target gene analysis revealed that the expression of heme oxygenase-1 (HO-1) was highly elevated by nano-Ag in nonspecific shRNA expressing cells, while Nrf2 knockdown cells (NRF2i) did not increase HO-1 expression. The role of HO-1 in cytoprotection against nano-Ag was reinforced by results using pharmacological inducer of HO-1: cobalt protoporphyrin-mediated HO-1 activation in the NRF2i cells prevented nano-Ag-mediated cell death. Similarly, pharmacological or genetic inhibition of HO-1 in nonspecific control cells exacerbated nano-Ag toxicity. As the upstream signaling mechanism, nano-Ag required the phosphoinositide 3-kinase (PI3K) and p38MAPK signaling cascades for HO-1 induction. The treatment with either PI3K inhibitor or p38MAPK inhibitor suppressed HO-1 induction and intensified nano-Ag-induced cell death. Taken together, these results suggest that Nrf2-dependent HO-1 up-regulation plays a protective role in nano-Ag-induced DNA damage and consequent cell death. In addition, nano-Ag-mediated HO-1 induction is associated with the PI3K and p38MAPK signaling pathways. PMID- 22036728 TI - Robust edge-directed interpolation of magnetic resonance images. AB - Image interpolation is intrinsically a severely under-determined inverse problem. Traditional non-adaptive interpolation methods do not account for local image statistics around the edges of image structures. In practice, this results in artifacts such as jagged edges, blurring and/or edge halos. To overcome this shortcoming, edge-directed interpolation has been introduced in different forms. One variant, new edge-directed interpolation (NEDI), has successfully exploited the 'geometric duality' that links the low-resolution image to its corresponding high-resolution image. It has been demonstrated that for scalar images, NEDI is able to produce better results than non-adaptive traditional methods, both visually and quantitatively. In this work, we return to the root of NEDI as a least-squares estimation method of neighborhood patterns and propose a robust scheme to improve it. The improvement is twofold: firstly, a robust least-squares technique is used to improve NEDI's performance to outliers and noise; secondly, the NEDI algorithm is extended with the recently proposed non-local mean estimation scheme. Moreover, the edge-directed concept is applied to the interpolation of multi-valued diffusion-weighted images. The framework is tested on phantom scalar images and real diffusion images, and is shown to achieve better results than the non-adaptive methods as well as NEDI, in terms of visual quality as well as quantitative measures. PMID- 22036729 TI - A new grapevine virus discovered by deep sequencing of virus- and viroid-derived small RNAs in Cv Pinot gris. AB - Field symptoms of chlorotic mottling and leaf deformations were observed on the cv Pinot gris (PG) in the Trentino region (Italy). Extensive assays excluded the presence of widely distributed nepo-, ampelo- and vitiviruses. An analysis of small RNA populations from two PG grapevines showing or not symptoms was carried out by Illumina high throughput sequencing. The study disclosed the virus and viroids contents of the two vines that was composed by Grapevine rupestris stem pitting-associated virus (GRSPaV), two viroids Hop stunt viroid (HSVd) and Grapevine yellow speckle viroid 1 (GYSVd1), the marafiviruses Grapevine rupestris vein feathering virus (GRVFV) and Grapevine Syrah virus 1 (GSyV-1), and a hitherto unrecorded virus. This virus had a genome organization identical to that of Grapevine berry inner necrosis virus (GINV), a trichovirus reported only from Japan, with which it grouped in phylogenetic trees constructed with sequences of the RdRp domain and the coat protein gene. However, molecular differences with GINV are wide enough to warrant classification of the virus in question as a new species, for which the provisional name of Grapevine Pinot gris virus (GPGV) is proposed. A limited field survey for the presence of GPGV in diseased and symptomless plants from three different cultivars did not allow to clearly associating the virus to the observed symptoms. PMID- 22036730 TI - The rotavirus enterotoxin (NSP4) promotes re-modeling of the intracellular microtubule network. AB - Expression of the rotavirus enterotoxin (NSP4) in transfected monkey kidney cells was found to result in a dramatic re-modeling of the microtubule (MT) network. This important centrosome organized cytoskeletal element was dissolved by expression of NSP4 and re-formed in a ring array at the periphery of the cell, similar to that seen following normal virus infection. Site directed mutagenesis of the N-linked glycosylation sites in NSP4 was employed to show that glycosylation of NSP4 was not required for it to promote changes in the MT network. This result together with experiments using conventional inhibitors indicated that NSP4's ability to cause elevation of intracellular calcium levels was also not necessary to effect the changes in the MT network. Use of the centrosome function inhibitor nocodazole demonstrated that NSP4 based remodeling of the MT network was dominant over the normal organizational role of the centrosome. Finally the remodeling of the MT network was shown not to be linked to cellular apoptosis or necrosis. The potential importance of this newly recognised role for NSP4 in the overall process of intracellular pathogenesis by rotaviruses is discussed. PMID- 22036731 TI - Evidence of two co-circulating genetic lineages of canine distemper virus in South America. AB - Canine distemper virus (CDV) is the etiological agent of a multisystemic infection that affects different species of carnivores and is responsible for one of the main diseases suffered by dogs. Recent data have shown a worldwide increase in the incidence of the disease, including in vaccinated dog populations, which necessitates the analysis of circulating strains. The hemagglutinin (H) gene, which encodes the major antigenic viral protein, has been widely used to determine the degree of genetic variability and to associate CDVs in different worldwide circulating lineages. Here, we obtained the sequence of the first full-length H gene of field South American CDV strains and compared it with sequences of worldwide circulating field strains and vaccine viruses. In South America, we detect two co-circulating lineages with different prevalences: the Europe 1 lineage and a new South America 2 lineage. The Europe 1 lineage was the most prevalent in South America, and we suggest renaming it the Europe 1/South America 1 lineage. The South America 2 lineage was found only in Argentina and appears related to wild CDV strains. All South American CDV strains showed high amino-acid divergence from vaccine strains. This genetic variability may be a possible factor leading to the resurgence of distemper cases in vaccinated dog populations. PMID- 22036732 TI - Successful control of vancomycin-resistant Enterococcus faecium nosocomial outbreak in a teaching hospital in China. AB - In 2008, a vancomycin-resistant enterococci outbreak occurred across 2 intensive care units in our hospital. This outbreak prompted us to implement intensified control measures. We describe the molecular epidemiology of the outbreak, as well as the intervention strategies that resulted in successful control of the outbreak. PMID- 22036733 TI - Mesenchymal stem cells from adipose tissue which have been differentiated into chondrocytes in three-dimensional culture express lubricin. AB - The present study focused on the isolation, cultivation and characterization of human mesenchymal stem cells (MSCs) from adipose tissue and on their differentiation into chondrocytes through the NH ChondroDiff medium. The main aim was to investigate some markers of biomechanical quality of cartilage, such as lubricin, and collagen type I and II. Little is known, in fact, about the ability of chondrocytes from human MSCs of adipose tissue to generate lubricin in three dimensional (3D) culture. Lubricin, a 227.5-kDa mucinous glycoprotein, is known to play an important role in articular joint physiology, and the loss of accumulation of lubricin is thought to play a role in the pathology of osteoarthritis. Adipose tissue is an alternative source for the isolation of multipotent MSCs, which allows them to be obtained by a less invasive method and in larger quantities than from other sources. These cells can be isolated from cosmetic liposuctions in large numbers and easily grown under standard tissue culture conditions. 3D chondrocytes were assessed by histology (hematoxylin and eosin) and histochemistry (Alcian blue and Safranin-O/fast green staining). Collagen type I, II and lubricin expression was determined through immunohistochemistry and Western blot. The results showed that, compared with control cartilage and monolayer chondrocytes showing just collagen type I, chondrocytes from MSCs (CD44-, CD90- and CD105- positive; CD45-, CD14- and CD34 negative) of adipose tissue grown in nodules were able to express lubricin, and collagen type I and II, indicative of hyaline cartilage formation. Based on the function of lubricin in the joint cavity and disease and as a potential therapeutic agent, our results suggest that MSCs from adipose tissue are a promising cell source for tissue engineering of cartilage. Our results suggest that chondrocyte nodules producing lubricin could be a novel biotherapeutic approach for the treatment of cartilage abnormalities. PMID- 22036734 TI - Carbon dots of different composition and surface functionalization: cytotoxicity issues relevant to fluorescence cell imaging. AB - Nanoscale carbon particles have emerged as versatile precursors for a new class of highly fluorescent nanomaterials that resemble semiconductor quantum dots. The surface-passivated fluorescent carbon nanoparticles, dubbed 'carbon dots', were already demonstrated for their potential optical bioimaging applications in vitro and in vivo. In this study, we conducted a systematic cytotoxicity evaluation on the carbon dots prepared by various combinations of precursor carbon nanoparticles and molecules for the particle surface functionalization. The results suggested that the cytotoxicity of carbon dots was dependent on the selection of surface passivation molecules. Those dots showing more significant cytotoxicity at higher concentrations were also evaluated for their effects on the fluorescence imaging of live cells. The implications of the results on the eventual use of carbon dots as cell imaging agents are discussed. PMID- 22036735 TI - Internet addiction: hours spent online, behaviors and psychological symptoms. AB - OBJECTIVE: The aim of this study was to investigate psychopathological symptoms, behaviors and hours spent online in patients with internet addiction disorder (IAD) at a new psychiatric service for IAD inside a policlinic. METHOD: Eighty six subjects participated in the study. Thirty-three patients asking for psychiatric consultation regarding their excessive use of the internet were assessed with IAD interview, internet addiction test (IAT), Symptom Checklist-90 Revised (SCL-90-R) and a brief sociodemographic survey. Moreover, patients had to respond to the following question: Over the last month, how much time have you spent online per week? At the end of psychiatric assessment, 21 of the 33 patients satisfied inclusion (IAD interview) and exclusion (psychotic disorders, neurocognitive deficits, dementia, serious mental delay, current alcohol or drug abuse) criteria. Twenty-one patients of the clinical group were compared with 65 subjects of a control group who were recruited online using IAT. RESULTS: IAD patients showed significantly higher scores on the IAT compared to subjects of the control group. Only item 7 (How often do you check your e-mail before something else that you need to do?) showed a significant inverse trend. SCL-90-R anxiety and depression subscale scores and item 19 (How often do you choose to spend more time online over going out with others?) of the IAT were positively correlated with number of weekly hours spent online in IAD patients. CONCLUSION: Findings suggest that a misuse of internet, characterized by many hours spent online avoiding interpersonal relationships with real and known people, could be an important criterion in the clinical interview in order to diagnose the IAD. The association between the lost interest in communicating with real people and psychological symptoms such as anxiety and depression could be relevant to detect IAD patients. PMID- 22036736 TI - Medication adherence and quality of life among Nigerian outpatients with schizophrenia. AB - OBJECTIVE: The aim of this study was to examine medication adherence among outpatients with schizophrenia in relation to their subjective quality of life and other sociodemographic, clinical and service related factors. METHODS: Three hundred and thirteen consecutive outpatient clinic attendees with a Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) diagnosis of schizophrenia confirmed with the Structured Clinical Interview for Diagnosis were recruited for the study. Respondents were interviewed using a questionnaire evaluating sociodemographic, medication, illness and clinic attendance related variables. Medication adherence was assessed using the Morisky medication adherence questionnaire. Participants also completed the World Health Organization Quality of Life Scale-BREF questionnaire as a measure of their subjective quality of life, while severity of illness was measured using the Brief Psychiatric Rating Scale (BPRS). RESULTS: Overall, 40.3% of the respondents were medication nonadherent. Medication adherent respondents significantly reported their perceived social support as "good" (P=.006), took significantly fewer number of medications (P<=.001), had higher medication use recall scores (P<=.001), had lower total BPRS scores (P=.001) and were "very satisfied" with their outpatient care (P=.002). Independent predictors of medication nonadherence were BPRS score [odds ratio (OR)=1.08, 95% confidence interval (95% CI)=1.03 1.13], outpatient clinic default (OR= 4.97, 95% CI=2.59-9.53) and moderate satisfaction with outpatient care (OR=2.78, 95% CI=1.47-5.24). Medication nonadherence was significantly associated with lower scores on all domains and facets of quality of life. CONCLUSIONS: Medication nonadherence is common among outpatients with schizophrenia and is associated with poor quality of life. Clinicians' awareness of the risk factors for medication nonadherence early in patients' management may significantly improve treatment outcomes, including patients' quality of life. PMID- 22036737 TI - Detoxification of high-dose zolpidem using cross-titration with an adequate equivalent dose of diazepam. AB - BACKGROUND: There have been numerous case reports of zolpidem abuse and dependence in the recent decade, giving rise to a focus on adverse withdrawal events such as seizure. No standard detoxification regimen has been proposed to date, despite the similarity of effects of zolpidem and benzodiazepines at high doses. CASE DESCRIPTIONS: We describe the results, in a 53-year-old female patient, of undergoing three different zolpidem detoxification programs. CONCLUSIONS: Because of her experiences, we recommend using the cross-titration strategy with an adequate equivalent dose of diazepam. PMID- 22036738 TI - Anxiety and depression in patients with myocardial infarction: findings from a centre in India. AB - OBJECTIVES: The study was conducted to assess the occurrence of anxiety and depression in patients with recent myocardial infarction (MI) and also to assess the relationship of these symptoms with other relevant factors and clinical outcome. METHODS: A total of 103 patients with recent MI attending the cardiology outpatient department (OPD) of a tertiary care centre in India were included. The patients were evaluated using Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D) and Mini International Neuropsychiatric Interview (MINI), and pertinent demographic and clinical parameters were recorded. The patients were followed up at 12 weeks telephonically to ascertain outcome. RESULTS: Significant anxiety and depressive symptoms were present in 48.5% and 25.2% of the sample. Anxiety or depressive disorder diagnosis was present in 25.2% of the sample. Aspirin use predicted lower anxiety and depressive symptom scores. A multivariate linear regression showed that female sex, history of angina and use of aspirin independently predicted scores on HAM-A. Diagnosis of psychiatric disorder, use of aspirin and increased body mass index also independently predicted scores on HAM-D. CONCLUSIONS: There is a need to screen for anxiety and depressive symptoms in patients with MI, so that appropriate intervention can be incorporated in the management plan. PMID- 22036739 TI - The management of pre-eclampsia: what we think we know. AB - The focus of this article is to review and challenge some current concepts surrounding the diagnosis and management of pre-eclampsia as well as considering where our management might head in the future. Pre-eclampsia is a syndrome defined by the new onset of hypertension in the 2nd half of pregnancy that is generally, but not always, accompanied by proteinuria. Whilst in recent times our understanding and management of this condition have improved there are some areas where evidence and opinions differ. In this review we will discuss the diagnosis of pre-eclampsia and the concept of the 'atypical' presentation. We will outline how to identify those women with pre-eclampsia who will have a poorer pregnancy outcome. We will address the question of when to deliver and how to treat if we decide to prolong the pregnancy. Finally we acknowledge that pre-eclampsia is more than a disorder of pregnancy and has lifelong implications for the mother and infant. PMID- 22036741 TI - More on color blindness. PMID- 22036742 TI - Increasing the dynamic range of in situ PLA. PMID- 22036744 TI - Taming the isobaric tagging elephant in the room in quantitative proteomics. PMID- 22036745 TI - High-throughput stem-cell niches. PMID- 22036746 TI - Characterizing RNA dynamics at atomic resolution using solution-state NMR spectroscopy. AB - Many recently discovered noncoding RNAs do not fold into a single native conformation but sample many different conformations along their free-energy landscape to carry out their biological function. Here we review solution-state NMR techniques that measure the structural, kinetic and thermodynamic characteristics of RNA motions spanning picosecond to second timescales at atomic resolution, allowing unprecedented insights into the RNA dynamic structure landscape. From these studies a basic description of the RNA dynamic structure landscape is emerging, bringing new insights into how RNA structures change to carry out their function as well as applications in RNA-targeted drug discovery and RNA bioengineering. PMID- 22036748 TI - GABA-B receptor: possible target for Parkinson's disease therapy. PMID- 22036749 TI - The use of NMR spectroscopy for identifying unknown foreign materials after aesthetic procedures. PMID- 22036747 TI - Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats. AB - In the spinal cord, neuron and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. However, in trauma or disease states, spinal glia become activated, dorsal horn neurons become hyperexcitable contributing to sensitized neuronal-glial circuits. The maladaptive spinal circuits directly affect synaptic excitability, including activation of intracellular downstream cascades that result in enhanced evoked and spontaneous activity in dorsal horn neurons with the result that abnormal pain syndromes develop. Recent literature reported that spinal cord injury produces glial activation in the dorsal horn; however, the majority of glial activation studies after SCI have focused on transient and/or acute time points, from a few hours to 1 month, and peri-lesion sites, a few millimeters rostral and caudal to the lesion site. In addition, thoracic spinal cord injury produces activation of astrocytes and microglia that contributes to dorsal horn neuronal hyperexcitability and central neuropathic pain in above-level, at-level and below level segments remote from the lesion in the spinal cord. The cellular and molecular events of glial activation are not simple events, rather they are the consequence of a combination of several neurochemical and neurophysiological changes following SCI. The ionic imbalances, neuroinflammation and alterations of cell cycle proteins after SCI are predominant components for neuroanatomical and neurochemical changes that result in glial activation. More importantly, SCI induced release of glutamate, proinflammatory cytokines, ATP, reactive oxygen species (ROS) and neurotrophic factors trigger activation of postsynaptic neuron and glial cells via their own receptors and channels that, in turn, contribute to neuronal-neuronal and neuronal-glial interaction as well as microglia-astrocytic interactions. However, a systematic review of temporal and spatial glial activation following SCI has not been done. In this review, we describe time and regional dependence of glial activation and describe activation mechanisms in various SCI models in rats. These data are placed in the broader context of glial activation mechanisms and chronic pain states. Our work in the context of work by others in SCI models demonstrates that dysfunctional glia, a condition called "gliopathy", is a key contributor in the underlying cellular mechanisms contributing to neuropathic pain. PMID- 22036750 TI - The relationship between adrenocortical function and Hsp70 expression in socially isolated Japanese quail. AB - Physiological responses to social isolation stress were compared in 56-day-old male Japanese quail. Birds were fed pretreated diets for 3 days as follows: (i) Basal diet (control); (ii) Basal diet+1500 mg/kg metyrapone (BM); (iii) Basal diet+30 mg/kg corticosterone (BCO); (iv) Basal diet+250 mg/kg ascorbic acid (BC); (v) Basal diet+250 mg/kg alpha-tocopherol (BE); (vi) Basal diet+250 mg/kg ascorbic acid and 250 mg/kg alpha-tocopherol (BCE). The birds were subsequently socially isolated in individual opaque brown paper box for 2 hours. Plasma corticosterone (CORT) concentration and heart and brain heat shock protein 70 (Hsp 70) expressions were determined before stress and immediately after stress. Two hours of isolation stress elevated CORT concentration significantly in the control and BE birds but not in the BC, BCE and BM birds. There was a significant reduction in CORT concentration after isolation stress in the BCO group. Isolation stress increased Hsp 70 expression in the brain and heart of control and BM birds. However, brain and heart Hsp 70 expressions were not significantly altered in the isolated BC, BCE and BE birds. Although, the CORT concentration of BM birds was not affected by isolation stress, Hsp70 expression in both brain and heart were significantly increased. Moreover, exogenous corticosterone supplementation did not result in elevation of Hsp 70 expression. It can be concluded that, although Hsp 70 induction had not been directly affected by CORT concentration, it may be modulated by the HPA axis function via activation of ACTH. PMID- 22036751 TI - [Identification of preterm labor: the role of the fibronectin and ultrasound cervicometry and their association]. AB - OBJECTIVE: The aim of this study was to evaluate the effectiveness of the fetal fibronetcin (fFN) test and ultrasonographic cervical length measurement used alone or in combination with each other in order to further improve the identification of patients in preterm labor. METHODS: Prospective multicenter observational study on patients between 24 and 32 weeks of gestation with symptoms of preterm labor (total patients = 132). The endpoint was the delivery at 34 weeks or more. The screening methods used were: the fFN test (group 1), the cervical length measurement by transvaginal ultrasound (group 2) or a combination of both tests (group 3) according to an established protocol. The statistical analysis was performed using the chi2 test using the SPSS software. RESULTS: Group 1: positive fFN test in 25.7% of cases, incidence of preterm birth (<34 weeks) of 18%. Group 2: cervical length <25 mm in 56.2% of cases, incidence of preterm birth (<34 weeks) of 18.5%. The negative predictive value is equivalent to 99.0% for the fFN test and 95.2% for cervicometry; combined use reaches 100%, compared to 54% positive predictive value. CONCLUSION: The identification of women at high risk of preterm delivery carried out with the fFN test or with transvaginal ultrasound cervicometry is clinically valid. The study also showed that the contextual use of biochemical and biophysical tests reaches a high negative predictive value (100%), making it a very useful method to identify patients truly at risk and to further reduce the incidence of non adequate treatment. PMID- 22036752 TI - Prenatal diagnosis of congenital rubella infection and ultrasonography: a preliminary study. AB - AIM: The aim of this study was to analyze the role of ultrasonography in the prenatal diagnosis of women with confirmed rubella infection in pregnancy. METHODS: We performed a retrospective, population-based study on 175 women referred to our Centre of Infectious Disease in Pregnancy of AOU Federico II for rubella infection, in the period between January 1999 and December 2009. In confirmed cases of infection we performed periodic ultrasonographic assessment of fetal anatomy looking for prenatal findings of rubeovirus infection. Neonatal outcomes were collected. RESULTS: Among 175 women, 48 (27.4%) were confirmed cases, in 83 (47.4%) cases rubella infection remain suspected. The remaining 44 (25.1%) women were excluded to having rubella infection in pregnancy. No defined probable cases were found. Among children born to mother with confirmed rubella infection, 9 (18.7%) resulted infected by rubella virus. In particular 6 newborns (66% of the affected) were asymptomatic, two babies showed incomplete congenital rubella syndrome (CRS), due to the presence of deafness in the absence of other congenital abnormalities without showing any USG findings. Only one baby showed a complete CRS: USG prenatal rubella infection findings were IUGR, polydramnios, cardiomegaly, defects of atrial septum, hepatosplenomegaly, ascites, echogenic bowel, placentomegaly. USG specificity and sensitivity was 100% and 11% respectively. CONCLUSION: USG has an important role in the detection rubella intrauterine infection in case of severe abnormalities. The obstetricians should understand the limitations of ultrasound in detection of deafness and minor abnormalities. PMID- 22036753 TI - Prenatal diagnosis of beta-thalassemia: nuchal translucency in affected fetuses. AB - AIM: Thalassemia syndromes are a group of blood disorders inherited in autosomal recessive manner. Prenatal diagnosis of disease is based on invasive procedures. Fetuses affected by homozygous thalassemia are not reported to be anemic. We studied their nuchal translucency (NT) measurements to identify as an ultrasonographic marker of disease and highlight any correlations. METHODS: Between April 2006 and July 2010 NT test was offered to women referred to our center for prenatal diagnosis of thalassemia. All the NT tests were performed in the time of chorionic villus sampling (CVS), according to the standards of the Fetal Medicine Foundation. Measurements of fetuses affected by homozygous thalassemia were compared with normal fetuses. RESULTS: A total of 55 fetuses were recruited. Of these, 15 were confirmed to be affected by homozygous thalassemia and 40 resulted to be carriers of thalassemia trait. Neither abnormal karyotype or structural abnormalities were detected and all the NT measurement were normal. NT was not different between the affected and normal fetuses. CONCLUSION: NT is not a marker of homozygous thalassemia in fetuses at risk. Invasive procedures remain the only available methods for diagnosis. PMID- 22036754 TI - [Clinical function of estrogen receptors in endometrial cancer]. AB - Approximately 70-80% of endometrial carcinomas, type I carcinomas, are associated with endometrial hyperplasia, hyperestrogenism, and expression of estrogen receptor (ER). The aim of this review was to clarify the role of ER in endometrial diseases carcinoma. The estrogens exert their effect via two estrogen receptor: alpha and beta. The ERs modulate transcriptional process by binding directly to the estrogen response elements (ERE) located in the target gene, or in non classical mode through protein-protein tethering with other transcription factors. There are also orphan receptors (their natural ligands have not been identified). Among this group, estrogen receptor-related receptors (ERRs) were identified by their sequences similar to those of ERs. Since the ERRs have shown a high similarity in DNA binding domain with ERs can interfere with estrogen signalling strengthening the hypothesis of an estrogen-ER-ERR crosstalk. Recently, the ERs and estrogen enzymes emerge as pharmacological targets in different disorders, as well as ERRs, and they may represent the reliable biomarkers in endometrial disease. PMID- 22036755 TI - [Materno-fetal conflicts and the perinatal Medea syndrome: a cognitive analysis]. AB - The definition of "maternal-fetal conflict" requires the attribution of a well defined subjectivity at the product of conception, and thus, from the medical point of view, we need to consider the fetus as a patient. A tangible example of conflict in our society is the "Medea syndrome", a framework in which the female parent kills her fetus or child to take revenge on the partner. We have produced a questionnaire that was administered to 150 women admitted to the Department of "Obstetrics and Gynecology" of the "Santa Maria della Misericordia" Hospital, in Perugia. The results show the importance of the maternal-fetal conflict in our reality through the opinion that women have given in assessing particular situations that we have proposed in the questionnaire. PMID- 22036756 TI - Fertility preservation for cancer patients. Current options. AB - Prevalence of cancer has been increasing in the last years. Fortunately, during the last three decades, there has been a tremendous improvement in the success rates of cancer treatments and a continual rise in the survival rates. Given the improvement in survival rates with cancer treatment and developments in the field of reproductive medicine, fertility preservation for female cancer patients has become a very sensible issue. Today, several methods are available for preserving the reproductive potential of these patients. This review will focus on the options for fertility preservation offered to young cancer patients. PMID- 22036757 TI - Eating disorders in the twenty-first century. AB - The first description of anorexia nervosa appeared in the literature over three hundred years ago. Since then, much has been learned about eating disorders, including the different presentations, medical complications, prognosis, and treatment strategies. In spite of this knowledge, the prevalence of eating disorders continues to grow. As well, eating disorders are seen in increasing frequency among males, children, and adults, and from all cultures and ethnicities. Of particular concern, is that patients with eating disorders often first present because of a complication such as amenorrhea, syncope, or abdominal pain, without disclosing the eating disorder. Therefore, all physicians should be aware of the various presentations of eating disorders, including the medical complications and risks, and be able to screen for a possible eating disorder. The major medical complications are due to the decreased caloric intake which leads to a hypometabolic state. While most complications are reversible with recovery, some, such as bone loss, may not be. Of particular concern during recovery is the possible development of a refeeding syndrome which occurs as the body goes from a catabolic to an anabolic state, causing hypophosphatemia, hypocalcemia and hypomagnesemia, which can lead to delirium, coma and death. Of further concern is that eating disorders have the highest mortality rate of all psychiatric disorders at 5.6% per decade. This article will review the changing demographics, medical complications, treatment options, and prognosis of eating disorders. PMID- 22036758 TI - Heavy menstrual bleeding in adolescents: hormonal or hematologic? AB - Adolescence in girls is marked by a host of physical and psychological changes including those associated with menstruation. Heavy menstrual bleeding is one of the most commonly encountered medical problems during transition from childhood to adulthood. Although common, it is likely underreported given that the definition is dependent upon personal experience and influenced by their perception of "normal". Anovulatory cycles related to an immaturity of the hypothalamic pituitary ovarian axis seems to be common, however bleeding disorders such as coagulation factor deficiencies including von Willebrand disease, and quantitative and qualitative abnormalities of platelets must be ruled out. Other medical conditions such as endocrinopathies including diabetes mellitus, Cushing syndrome, polycystic ovarian syndrome, hypothyroidism, chronic hepatic and renal disease, anatomical uterine anomalies, pregnancy, obesity, medications causing hyperprolactinemia must also be considered. Management is based on the presence of hemodynamic instability and acuity of presentation. Treatment options include the use of combined oral contraceptive pills and antifibrinolytic agents; levonorgesterel impregnated intrauterine devices and or treatment of the specific underling bleeding disorder or endocrinopathy. Ongoing management needs to be accomplished through a multi disciplinary team approach in a comprehensive care setting with an adolescent gynecologist, hematologist, pediatrician, and nutritionist involved in the program for a better outcome of this problem. PMID- 22036759 TI - Endometrial seedlings. A survival instinct? Immunomodulation and its role in the pathophysiology of endometriosis. AB - Endometriosis occurs when ectopic cells from the endometrium implant within the peritoneum. It is considered as a disease of multifactorial aetiology and affects 7-10% of women of reproductive age worldwide. In endometriosis, the immune system is thought to be dysfunctional and various studies have shown cytokine imbalance. Commonly upregulated cytokines include Tumour necrosis factor-alpha, interferon gamma and interleukin-10. Through analysis of the molecular makeup of the peritoneal fluid, a change is shown to occur, conferring resistance from macrophages and lymphocytes to endometrial cells. This is possibly due to a reduced Inter-cellular adhesion molecule-1 synthesis. Survival of ectopic endometrial cells also arises through the expression of human leukocyte antigens. Apart from the survival of ectopic/eutopic cells in endometriosis, there is marked cellular proliferation, which has also been attributed to a change in the expression of proteins such as Bcl-2-Associated X protein, B-cell lymphoma-2 protein, transforming growth factor-beta and the enzyme aromatase. Danazol and aromatase inhibitors modulate the immune system, thus allowing partial restoration of cytokine levels. Pharmacogenomics may be the way forward in developing novel treatment modalities for endometriosis. PMID- 22036760 TI - Update in endometriosis and IVF. AB - The impact of endometriosis on in vitro fertilization (IVF) has been the subject of numerous publications, although a number of critical issues related to the management of affected patients remain unsolved. Accurate assessment of the effect of this disease on IVF outcome requires an appraisal of the diagnostic limitations, the consequences of surgical and hormonal management of endometriosis and the potential impact of both disease and IVF on feto-maternal well-being. We have addressed all these aspects by attempting an overview of the literature of the last decade and we present an update which may be useful regarding the treatment options of subfertile women seeking pregnancy. PMID- 22036761 TI - The cytotoxic effects of bendamustine in combination with cytarabine in mantle cell lymphoma cell lines. AB - Bendamustine is clinically useful in mantle-cell lymphoma (MCL). Its favorable toxicity profile in-vivo favors its combination with other cytotoxic drugs. Cytarabine is a key drug in the treatment of younger patients with MCL. The current study investigated the in-vitro cytotoxic effect of bendamustine and cytarabine, alone or combined, on two MCL cell lines representing the classic and blastoid variant of the lymphoma subtype (JEKO-1 and GRANTA-519). Cell lines were exposed to each drug alone, or simultaneously and consecutively to both drugs, for different time schedules. Apoptosis was measured by flow cytometry. Mitochondrial damage, cell proliferation/metabolic activity, and cell cycle analysis were also assessed. The synergistic, additive, or antagonistic effects of the drugs were calculated with the combination index (CI) method. Bendamustine and cytarabine alone exhibited relevant cytotoxic activity on both cell lines. Both drugs induced cell cycle arrest in S phase. Drug combinations were associated with significantly higher cytotoxic effects than each drug alone. Among the combination schedules, the consecutive incubation of bendamustine followed by cytarabine was associated with the lower CI, being 10-100-fold lower than with simultaneous incubations. The cytotoxic effect of the consecutive combination was prominent on both cell lines, indicating a very strong and highly significant synergy in inducing apoptosis. Similar results were obtained measuring mitochondrial damage or the decline of the metabolic activity in all cell lines. The strong synergistic effect of bendamustine and cytarabine on MCL cells provides a rationale for developing schedules combining these agents in the treatment of MCL. PMID- 22036762 TI - The modifying effect of Xmn1-HBG2 on thalassemic phenotype is associated with its linked elements in the beta globin locus control region, including the palindromic site at 5'HS4. AB - The core sequence of 5'HS4-beta globin locus control region and Xmn1-HBG2 site were analyzed and compared among 86 thalassemia patients with homozygous or compound heterozygous beta globin gene mutations and 101 normal individuals. Frequency of the G allele in the polymorphic palindromic sequence of 5'HS4 (TGGGG A/G CCCCA) and positive Xmn1-HBG2 profile was significantly higher in thalassemia patients compared to the normal population. Linkage disequilibrium was observed between the G allele and positive Xmn1-HBG2 profile in patient population. Furthermore, dominance of IVSII-1 in the mutation spectrum of the patients enabled us to identify linkage disequilibrium relationships between IVSII-1, positive Xmn1-HBG2 and the G allele at 5'HS4. The frequency of milder clinical phenotype was significantly higher in patients with GG/++ than cases with AA/-- genotypic pattern in 5'HS4/Xmn1-HBG2 loci. These data together with biochemical evidence suggesting a role for the A/G polymorphism at 5'HS4 palindromic site on modifying chromatin structure and in the absence of any evidence from functional studies relating the Xmn1-HBG2 site to the increased gamma chain expression, suggest that the phenotype modifying role long time assigned to Xmn1-HBG2 is possibly played by more functionally potent elements linked to it in LCR. PMID- 22036763 TI - Hydrogen peroxide induces Sp1 methylation and thereby suppresses cyclin B1 via recruitment of Suv39H1 and HDAC1 in cancer cells. AB - Sp1 is an important transcription factor for a number of genes that regulate cell growth and survival. Sp1 is an anchor protein that recruits other factors to regulate its target genes positively or negatively, but the mechanism of its functional switch by which positive or negative coregulators are recruited is not clear. In this study, we found that Sp1 could be methylated and that methylation was maintained by treatment with pargyline, a lysine-specific demethylase 1 (LSD1) inhibitor or knock LSD1 down directly. Hydrogen peroxide treatment increased the methylation of Sp1 and repressed Sp1 transcriptional activity. Investigation of the mechanism by which methylation decreased Sp1 activity found that methylation of Sp1 increased the recruitment of Su(var) 3-9 homologue 1(Suv39H1) and histone deacetylase 1 (HDAC1) to the cyclin B1 promoter, resulting in deacetylation and methylation of histone H3 and subsequent downregulation of cyclin B1. Finally, downregulation of cyclin B1 led to cell cycle arrest at the G2 phase. These results show that methylation of Sp1 causes it to act as a negative regulator by recruiting Suv39H1 and HDAC1 to induce chromatin remodeling. This finding that methylation acts as a functional switch provides new insight into the modulation of Sp1 transcriptional activity. PMID- 22036764 TI - LC-MS method for screening unknown microbial carotenoids and isoprenoid quinones. AB - The structure of secondary metabolites from microorganisms provides a useful tool for microbial characterization and chemotaxonomic classification. Microbial isoprenoid quinones, for example, are well described and used to distinguish among photosynthetic microorganism groups. In addition, isoprenoid quinones can also be found, together with carotenoids, in non-photosynthetic microorganisms. The aim of the present study was to develop a LC-MS/MS method which can analyze and identify these microbial isoprenoids. Positive atmospheric pressure chemical ionization (APCI) together with collisionally induced dissociation was applied for generation of informative fragment spectra by mass spectrometry. Enhanced product ion (EPI) scan in a linear ion trap with information dependent data acquisition (IDA) enabled generation of MS fragment data even from minor isoprenoids. The developed liquid chromatography method enabled separation of isoprenoid patterns from their ester derivatives. Discovery and structural characterization of isoprenoid quinones and carotenoids were carried out by comparing characteristics of fragment spectra from unknown compounds with fragment spectra of a range of isoprenoid standard compounds and using published data. Throughout the study 17 microorganisms (e.g., Acremonium butyri, Arthrobacter spp., Brevibacterium linens, Bullera variabilis, Exophiala dermatitidis, Lecythophora hoffmannii, Panthoea agglomerans, Rhodotorula spp., Xanthophyllomyces dendrorhous) were screened and probable structures of isoprenoid quinones and carotenoids were suggested. The method lays some foundations on the analysis of yet unknown isoprenoids in microorganisms by using LCMS/MS techniques. PMID- 22036765 TI - Midterm outcome of arthroscopic revision repair of massive and nonmassive rotator cuff tears. AB - PURPOSE: The purpose of this study was to evaluate the midterm functional outcome of arthroscopic revision rotator cuff repair and compare the outcomes of nonmassive and massive rotator cuff tears. METHODS: We performed a retrospective review of patients over a 10-year period who underwent arthroscopic revision rotator cuff repair. The cohort was divided into 2 groups based on tear size (nonmassive and massive tears). RESULTS: The cohort consisted of 21 nonmassive tears and 53 massive tears with a mean follow-up of 63 months. The 2 groups had similar baseline characteristics. In the overall cohort, after arthroscopic revision repair, there was a significant reduction in pain (P < .001) and increase in active forward elevation (P = .003) and functional outcome by American Shoulder and Elbow Surgeons score (P < .001) and University of California, Los Angeles score (P < .001). The rate of patient satisfaction was 78%. There was no significant difference between the 2 groups (nonmassive v massive) in postoperative forward elevation, pain, or functional outcome. A poor functional outcome according to the University of California, Los Angeles score was associated with female sex (P = .005), preoperative active forward flexion below 136 degrees (P = .004), and preoperative pain score greater than 5 points (P = .002). CONCLUSIONS: The results of this study suggest that arthroscopic revision rotator cuff repair is a reasonable treatment option, even in cases of massive retears. Tear size does not appear to affect final outcome. This technique can yield reliable improvements in active forward elevation and functional outcome and a decrease in pain at an acceptably high rate in this difficult patient population. Female sex, preoperative forward elevation less than 136 degrees , and preoperative pain score greater than 5 points are poor prognostic risk factors for obtaining a satisfactory functional outcome with arthroscopic revision repair. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 22036766 TI - Aminoguanidine and curcumin attenuated tumor necrosis factor (TNF)-alpha-induced oxidative stress, colitis and hepatotoxicity in mice. AB - The up regulation of gut mucosal cytokines such as tumor necrosis factor (TNF) alpha and oxidative stress have been related to inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). This study investigated an immune-mediated model of colitis. TNF-alpha injected intraperitonally to mice induced a dose-dependent recruitment of neutrophils into abdominal mesentery. The leukocytes influx induced by TNF-alpha (10 MUg kg(-1) body weight) increased by 3 fold liver and colon damage scores. TNF-alpha-colitis was characterized by hemorrhagic edemas and crypt abscesses massively infiltrated by inflammatory cells, namely neutrophils. Moreover, TNF-alpha-toxicity resulted in liver steatosis and foci of necrosis infiltrated by Kupffer cells and neutrophils in parenchyma and around the centrilobular veins. The involvement of oxidative stress was evaluated using aminoguanidine (AG) as selective inhibitor of inducible NO synthase (iNOS) and curcumin (Cur), the polyphenolic antioxidant of turmeric (Curcuma longa L.). TNF-alpha-toxicity led to significant increase in myeloperoxidase (MPO, an index of neutrophils infiltration), nitrites (stable nitric oxide metabolites) and malondialdehyde (MDA, a marker of lipid peroxides) levels and cell apoptosis in liver and colon. AG and Cur treatments significantly attenuated the hallmarks of oxidative stress, neutrophils influx and ROS-related cellular and histological damages, in TNF-alpha-treated mice. Taken together, our results provide insights into the role of phagocytes-derived oxidants in TNF alpha-colitis in mice. Cur and AG, by inhibiting neutrophils priming and iNOsynthase could be effective against oxidative bowel damages induced in IBD by imbalanced gut immune response. PMID- 22036767 TI - Re: personalized medicine and cancer supportive care: appropriate use of colony stimulating factor support of chemotherapy. PMID- 22036768 TI - Expanding views of presynaptic terminals: new findings from Caenorhabditis elegans. AB - The unique ability of chemical synapses to transmit information relies on the structural organization of presynaptic terminals. Empowered by forward genetics, research using Caenorhabditis elegans has continued to make pivotal contributions to discover conserved regulators and pathways for presynaptic development. Recent advances in microscopy have begun to pave the path for linking molecular dynamics with subsynaptic structures. Studies using diverse reporters for synapses further broaden the landscape of regulatory mechanisms underlying presynaptic differentiation. The identification of novel regulators at transcriptional and post-transcriptional levels raises new questions for understanding synapse formation at the genomic scale. PMID- 22036769 TI - Functional regulation of GABAA receptors in nervous system pathologies. AB - Inhibitory neurotransmission is primarily governed by gamma-aminobutyric acid (GABA) type A receptors (GABAARs). GABAARs are heteropentameric ligand-gated channels formed by the combination of 19 possible subunits. GABAAR subunits are subject to multiple types of regulation, impacting the localization, properties, and function of assembled receptors. GABAARs mediate both phasic (synaptic) and tonic (extrasynaptic) inhibition. While the regulatory mechanisms governing synaptic receptors have begun to be defined, little is known about the regulation of extrasynaptic receptors. We examine the contributions of GABAARs to the pathogenesis of neurodevelopmental disorders, schizophrenia, depression, epilepsy, and stroke, with particular focus on extrasynaptic GABAARs. We suggest that extrasynaptic GABAARs are attractive targets for the treatment of these disorders, and that research should be focused on delineating the mechanisms that regulate extrasynaptic GABAARs, promoting new therapeutic approaches. PMID- 22036770 TI - Xenoestrogenic chemicals effectively alter sperm functional behavior in mice. AB - Xenoestrogenic compounds (XCs) can disrupt endogenous hormone function and affect sperm function by binding to receptors on sperm membrane. Albeit spermatozoa are potentially a useful model for screening estrogenic activities of endocrine disruptors, high-quality in vitro test system that examination of the XCs effects on sperm function is required. The objective of this study was to compare the effects of XCs (genistein and 4-tert-octylphenol) to those of steroids (estrogen and progesterone) and heparin on in vitro capacitation and acrosome reaction (AR) in mouse spermatozoa. Mouse spermatozoa were incubated with various concentrations (0.001-100 MUM) of each chemical for 15 or 30 min, and then capacitation and AR were assessed using chlortetracycline. All chemicals studied effectively alter capacitation and/or AR in mouse spermatozoa with different manner. Therefore, we believed that our system will provide a good in vitro model system to characterize the physiological effect of XCs especially when compared with steroids. PMID- 22036771 TI - Psychological distress among women with newly diagnosed breast cancer. AB - PURPOSE: Psychological distress is common in the cancer continuum. Our objectives were to determine the prevalence of distress and to investigate the related problems and the characteristics of women with breast cancer who experienced psychological distress at the time of diagnosis. METHODS: We used cross-sectional data from a questionnaire study. Women with newly diagnosed breast cancer were consecutively invited to respond before breast surgery. Between October 2008 and October 2009, a total of 357 responded out of 426 (84%) invited. Among these, 343 patients completed the 'distress thermometer' to measure psychological distress and the accompanying 'problem list' to identify related problems. Logistic regression models with 95% confidence intervals were used to estimate the associations between psychological distress, age, social support and domains on the problem list. RESULTS: With a cut-off of 3 on the distress thermometer, 77% of women with breast cancer reported distress, whereas when the cut-off was 7, 43% were distressed. The mean distress score was 5.4 (SD, 3.1). The most frequently reported problems were worry (77%) and nervousness (71%). Distress was significantly associated with the total score and three domains on the problem list. Younger women (<50 years) reported higher levels of distress than older (>= 50 years). We found no significant association between distress and having a partner or someone outside the family to rely on. CONCLUSIONS: Distress was reported by 77% of patients. Age and problem list were significantly associated with distress. No significant association between psychological distress and social support was observed. PMID- 22036772 TI - Colorectal cancer screening behaviour and associated factors among Chinese aged 50 and above in Hong Kong - a population-based survey. AB - PURPOSE: This study reports the uptake rate of colorectal cancer screening among Chinese people aged 50 or above and the identified factors associated with the likelihood of undergoing such screening. METHODS: A cross-sectional population based telephone survey was conducted in Hong Kong during the period 2 to 28 May 2007. The survey covered demographics, perceived health status and susceptibility to cancer, utilisation of complementary medicine, family history of cancer and cancer screening behaviour. RESULTS: The survey was completed by 2004 Hong Kong Chinese residents aged 50 or older (response rate = 66.6%). The uptake rate of a fecal occult blood test and a colonoscopy was 12% and 19% respectively. Factors associated with colorectal cancer screening behaviour included: male participants, ex-smokers, with cancer or other serious disease, a family history of cancer, perceived health status fair or poor, regular visits to a doctor to look after health, and utilisation of complementary medicine. CONCLUSIONS: The uptake rate of this study population was low though an increasing trend did appear. Heath education and promotion programmes may focus on these identified factors to facilitate colorectal cancer screening in a Chinese population. PMID- 22036773 TI - Patient's sexuality - a neglected area of cancer nursing? AB - PURPOSE: The purpose of this study was to describe nurses' conceptions of dialogues about sexuality with cancer patients. METHODS: The study was carried out using phenomenographic method. Ten nurses from different care contexts where nurses meet cancer patients in various phases of trajectory of care were interviewed. RESULTS: The analysis revealed one main category 'We should talk about sexuality - but we usually don't' and three descriptive categories consisting of nurses' qualitatively different conceptions of talks about sexuality: (1) nurses' attitudes, knowledge and skills are impacting, (2) patients' sexual problems are the basis for dialogues and (3) the ward environment is impacting. The main category was hierarchically ranged and could be further understood by the descriptive categories. CONCLUSION: The study showed that cancer patients' need of talks about and support regarding sexuality were conceived as being low during the whole trajectory of care. Despite this the nurses conceived that they should talk about sexuality with the patients, but due to own attitudes, knowledge and skills, as well as conditions in the ward environment they usually did not. Further studies are needed to clarify how cancer patients especially with non-sex specific diagnosis describe their sexual problems and needs of support in regard to sexuality. About what, when, how and by whom, cancer patients and their partners want information and supportive care related to sexuality need to be clarified. PMID- 22036774 TI - Pharmacological blockade of corticotropin-releasing hormone receptor 1 (CRH1R) reduces voluntary consumption of high alcohol concentrations in non-dependent Wistar rats. AB - BACKGROUND: A dysregulation of the corticotropin-releasing hormone (CRH) system has been implicated in the development of excessive alcohol consumption and dependence. The aim of the present study was to evaluate whether the CRH system is also recruited when non-dependent Wistar rats escalate to high alcohol intake in the intermittent (alternate days) model of drinking. METHODS: We compared intermittent and continuous access to 20% (v/v) alcohol in a two-bottle free choice drinking paradigm. Following a total of twenty 24-hour exposures for every experimental group, we assessed signs of alcohol withdrawal, including anxiety like behavior and sensitivity to stress. The selective CRH1 receptor (CRH1R) antagonist antalarmin (0, 10, 20 mg/kg, i.p.) was tested on alcohol consumption. RESULTS: Intermittent access to 20% alcohol led non-selected Wistar rats to escalate their voluntary intake to a high and stable level, whereas continuously exposed animals maintained a lower consumption. These groups did not differ in physical withdrawal signs. In addition, no differences were found when anxiogenic like behavior was studied, neither under basal conditions or following restraint stress. Nevertheless, sensitivity to the treatment with the CRH1R antalarmin was observed since a reduction of 20% alcohol intake was found in both groups of animals regardless of the regimen of alcohol exposure. In addition, antalarmin was effective when injected to animals exposed to intermittent 10% (v/v) alcohol whereas it failed to suppress 10% continuous alcohol intake. CONCLUSIONS: Pharmacological blockade of CRH1R reduced alcohol drinking when sustained high levels of intake were achieved suggesting that the CRH system plays a key role when high doses of ethanol are consumed by non-dependent subjects. This supports the notion that CRH system not only maintains the dependent state but also engages the transition to dependence. PMID- 22036775 TI - A new and highly prognostic system to discern T1 bladder cancer substage. AB - BACKGROUND: Management of T1 bladder cancer (BCa) is controversial. OBJECTIVE: Evaluate the impact of substage on the clinical outcome of T1 BCa. DESIGN, SETTING, AND PARTICIPANTS: The T1 diagnosis of 134 first-diagnosis BCa patients from two university hospitals was confirmed. For the T1 substage, we used a new system that discerns T1-microinvasive (T1m) and T1-extensive-invasive (T1e) tumors. We then determined the invasion of the muscularis mucosae-vascular plexus (MM-VP): T1a (invasion above the MM-VP), T1b (invasion in the MM-VP), or T1c (invasion beyond the MM-VP). If the MM-VP was not present at the invasion front, the case was assigned to T1a or T1c. All patients were initially managed conservatively (with bacillus Calmette-Guerin). MEASUREMENTS: Multivariable analyses for progression and disease-specific survival (DSS). RESULTS AND LIMITATIONS: Median follow-up was 6.4 yr (interquartile range: 3.3-9.2 yr). Progression to >= T2 was observed in 40 patients (30%), and 19 patients (14%) died of BCa. The MM-VP was not present at the invasion front in 50 patients (37%). T1 substage was as follows: 40 T1m and 94 T1e; 81 T1a, 18 T1b, and 35 T1c. In multivariable analyses, substage (T1m/T1e) was significant for progression (p=0.001) and DSS (p=0.032), whereas substage according to T1a/T1b/T1c was not significant. Female gender (p=0.006) and carcinoma in situ (p=0.034) were also significant predictors of progression. The main limitation to the study is absence of a repeat transurethral resection. CONCLUSIONS: Substage according to the new system (T1m and T1e) was user-friendly, possible in 100% of cases, and very predictive of T1 BCa behavior. Future studies may ultimately lead to the incorporation of this new substaging system in the TNM classification system for urinary BCa. PMID- 22036776 TI - Efficacy and safety of low doses of onabotulinumtoxinA for the treatment of refractory idiopathic overactive bladder: a multicentre, double-blind, randomised, placebo-controlled dose-ranging study. AB - BACKGROUND: In the treatment of patients with idiopathic overactive bladder (iOAB), high doses of botulinum toxin type A (BoNTA) were often associated with complications resulting from high postvoid residuals (PVR), leading to clean intermittent catheterisation (CIC) and urinary tract infections (UTI). OBJECTIVE: Evaluate the efficacy and tolerability of low doses of onabotulinumtoxinA compared to placebo in patients with iOAB. DESIGN, SETTING, AND PARTICIPANTS: Between 2005 and 2009, adults with persistent iOAB were included in a prospective, randomised, double-blind, placebo-controlled comparative trial. INTERVENTION: Patients were randomised to undergo a single intradetrusor injection procedure of either placebo or onabotulinumtoxinA (50 U, 100 U or 150 U). MEASUREMENTS: The initial evaluations (ie, clinical and urodynamic variables as well as quality of life [QoL]) were repeated at day 8 and months 1, 3, 5, and 6. RESULTS AND LIMITATIONS: Ninety-nine patients were included in the efficacy analysis. Three months after the procedure, we observed>50% improvement versus baseline in urgency and urge urinary incontinence (UUI) in 65% and 56% of patients who respectively received 100 U (p=0.086) and 150 U (p=0.261) BoNTA injections and >75% improvement in 40% of patients of both groups (100 U [p=0.058] and 150 U [p=0.022]). Complete continence was observed in 55% and 50% patients after 100 U and 150 U BoNTA treatment, respectively, at month 3. Frequency symptoms and QoL improved up to the 6-mo visit. We observed only three patients with a PVR>200 ml in the 150 U group and a few UTIs. CONCLUSIONS: 100 U and 150 U BoNTA injections were well tolerated and have both shown to improve symptoms and QoL in patients with iOAB. Nevertheless, 100 U injections showed a reasonable efficacy, with a lower risk of high PVR. TRIAL REGISTRATION: ClinicalTrials.gov NCT00231491. PMID- 22036777 TI - Postoperative radiation therapy for pathologically advanced prostate cancer after radical prostatectomy. AB - CONTEXT: Approximately 15-25% of men who undergo radical prostatectomy for localized prostate cancer (PCa) will experience recurrence of their cancer; men with poorly differentiated cancer, non-organ-confined disease, and positive surgical margins are at the highest risk. OBJECTIVE: Review accumulating evidence indicating that postoperative radiotherapy (RT) to the prostate bed favorably influences the course of disease in men with adverse pathologic features. EVIDENCE ACQUISITION: Three phase 3 randomized trials of adjuvant RT versus observation have reported improved freedom from biochemical recurrence (BCR) and local control: Southwest Oncology Group (SWOG) 8794, European Organization for Research and Treatment of Cancer (EORTC) 22911, and the German Cancer Society (ARO 96-02). EVIDENCE SYNTHESIS: Conflicting evidence from these trials suggests that adjuvant RT can have a favorable impact on systemic progression, PCa specific mortality, or overall survival. Observational studies have reported durable responses to salvage RT in a substantial proportion of high-risk patients (provided that it is administered at the earliest evidence of BCR) and reduced PCa-specific mortality. There is consensus that the outcome of patients receiving postoperative RT is best when the prostate-specific antigen (PSA) level is the lowest. However, it is unclear if better outcomes will be achieved administering adjuvant RT to all patients at increased risk for recurrent PCa who have an undetectable postoperative PSA level compared to close observation and timely salvage RT at the earliest indications of BCR. CONCLUSIONS: Given the absence of data from randomized trials demonstrating superiority of one approach over the other in terms of quantity and quality of life, we advocate multidisciplinary input and shared and informed decision making among patients, urologists, and radiation oncologists based on the relative advantages and disadvantages of each approach. PMID- 22036778 TI - Re: Seong Cheol Kim, Cheryn Song, Wansuk Kim, et al. Factors determining functional outcomes after radical prostatectomy: robot-assisted versus retropubic. Eur Urol 2011;60:413-9. PMID- 22036779 TI - Persistent abdominal pain and pyrexia after combined radiofrequency ablation and TACE. PMID- 22036780 TI - Bleeding duodenal mass. PMID- 22036781 TI - Submucosal tumor of cecum? PMID- 22036782 TI - An unusual cause of pancreatitis. PMID- 22036783 TI - Endoscopic ultrasonography in upper gastrointestinal bleeding: diagnostic challenge with therapeutic value. PMID- 22036784 TI - Purification and functional inactivation of the fission yeast MCM(MCM-BP) complex. AB - The MCM (mini-chromosome maintenance) complex is the core of the eukaryotic replicative helicase and comprises six proteins, Mcm2-Mcm7. In humans, a variant form of the complex has Mcm2 replaced by the MCM-BP protein. Recent results suggest that a similar complex exists in fission yeast with an essential role in DNA replication and cell cycle progression. Here, we describe the purification and subunit composition of the fission yeast MCM(Mcb1) complex. Using newly generated temperature-sensitive alleles, we show that loss of MCM(Mcb1) function leads to accumulation of DNA damage, checkpoint activation and cell cycle arrest, and provide evidence for a role for MCM(Mcb1) in meiosis. PMID- 22036785 TI - Wiskott-Aldrich Syndrome at the nexus of autoimmune and primary immunodeficiency diseases. AB - Wiskott-Aldrich Syndrome (WAS) is a X-linked primary immunodeficiency disorder also marked by a very high (up to 70%) incidence of autoimmunity. Wiskott-Aldrich Syndrome arises from mutations in the Wiskott-Aldrich Syndrome protein (WASp), a cytoplasmic protein that links signaling by cell surface receptors such as the T cell receptor and integrins to actin polymerization. WASp promotes the functions of multiple cell types that support immune responses, but also is important for the function of regulatory T cells and in TCR-induced apoptosis, two negative mechanisms of immune regulation that maintain peripheral immune tolerance. Here we review the nature of immune defects and autoimmunity in WAS and WASp deficient mice and discuss how this single gene defect can simultaneously impair immune responses to pathogens and promote autoimmunity. The myriad cellular immune defects found in WAS make this Mendelian syndrome an interesting model for the study of more complex immune diseases that arise from the interplay of environmental and multiple genetic risk factors. PMID- 22036786 TI - PKA-dependent regulation of Cdc25 RasGEF localization in budding yeast. AB - In Saccharomyces cerevisiae the Cdc25/Ras/cAMP pathway is involved in cell growth and proliferation regulation. Ras proteins are regulated by Ira1/2 GTPase activating proteins (GAPs) and Cdc25/Sdc25 guanine nucleotide exchange factors (GEFs). Most of cytosolic Cdc25 protein was found on internal membranes in exponentially growing cells, while upon incubation in a buffer with no nutrients it is re-localized to plasma membrane. The overexpression of Tpk1 PKA catalytic subunit also induces Cdc25 export from the nucleus, involving two serine residues near the Nuclear Localization Site (NLS): mutation of Ser(825) and Ser(826) to glutamate is sufficient to exclude physiologically expressed Cdc25 from the nucleus, mimicking Tpk1 overproduction effect. Mutation of these Ser residues to Ala abolishes the effect of nuclear export induced by Tpk1 overexpression on a Cdc25eGFP fusion. Moreover, mutation of these residues affects PKA-related phenotypes such as heat shock resistance, glycogen content and cell volume. PMID- 22036787 TI - Plant hemoglobins: important players at the crossroads between oxygen and nitric oxide. AB - Plant hemoglobins constitute a diverse group of hemeproteins and evolutionarily belong to three different classes. Class 1 hemoglobins possess an extremely high affinity to oxygen and their main function consists in scavenging of nitric oxide (NO) at very low oxygen levels. Class 2 hemoglobins have a lower oxygen affinity and they facilitate oxygen supply to developing tissues. Symbiotic hemoglobins in nodules have mostly evolved from class 2 hemoglobins. Class 3 hemoglobins are truncated and represent a clade with a very low similarity to class 1 and 2 hemoglobins. They may regulate oxygen delivery at high O(2) concentrations. Depending on their physical properties, hemoglobins belong either to hexacoordinate non-symbiotic or pentacoordinate symbiotic groups. Plant hemoglobins are plausible targets for improving resistance to multiple stresses. PMID- 22036788 TI - Association of Mycobacterium tuberculosis genotypes and clinical and epidemiological features - a multi-center study in Taiwan. AB - Genotypes of Mycobacterium tuberculosis (MTB) are related to the geographic origin of the patients and population migration. The relationship between genotypes of MTB and clinical presentations has mainly focused on transmission of multi-drug resistant MTB strain in population. This study aimed to investigate the molecular epidemiology and dynamic change of MTB genotypes in Taiwan, and their association with clinical presentation among patients with pulmonary tuberculosis. A multi-center, two-year study which enrolled 516 patients with 516 MTB isolates was conducted, including: (1) 254 isolates from northern Taiwan; (2) 38 isolates from mid-western Taiwan; (3) 211 isolates from southern Taiwan; and (4) 13 isolates from the east coast of Taiwan. The isolates were genotyped with spoligotyping and standardized 12-loci-MIRU-VNTR method. The results showed Beijing/Beijing-like family was the major genotype of MTB in the northern (58%), eastern (53%), and southern (33%) regions. The second most widely spread lineage were the EAI-Manila (20% in the west and south) and Haarlem family (13-27% in the south, west, and east). According to the cluster analysis of 12-MIRU-VNTR genotypes, there were differences in distribution of MTB genotype between the northern and southern regions, and a temporal relationship between isolation year and 12-MIRU-VNTR genotype especially in loci 26 and 39 might exist. Furthermore, some patients with cavity lesions on chest films were associated with a cluster of Beijing family MTB strains, which can be defined by cluster analysis of 12 MIRU-VNTR genotype. However, the results of 12-loci-MIRU-VNTR genotyping in a longitudinal study should be interpreted with caution due to its short term instability. Further investigations of different molecular methodologies are necessary. PMID- 22036789 TI - Molecular epidemiology and evolutionary dynamics of betanodavirus in southern Europe. AB - Viral encephalopathy and retinopathy (VER) is one of the most devastating diseases for marine aquaculture, and similarly represents a threat to wild fish populations because of its high infectivity and broad host range. Betanodavirus, the causative agent of VER, is a small non-enveloped virus with a bipartite RNA genome comprising the RNA1 and RNA2 segments. We partially sequenced both RNA1 and RNA2 from 120 viral strains isolated from 2000 to 2009 in six different countries in Southern Europe. Phylogenetic analysis revealed the presence of the red-spotted grouper nervous necrosis virus (RGNNV) (n=96) and striped jack nervous necrosis virus (SJNNV) (n=1) genotypes in Southern Europe, with 23/120 samples classified as RGNNV/SJNNV reassortants. Viruses sampled from individual countries tended to cluster together suggesting a major geographic subdivision among betanodaviruses, although some phylogenetic evidence for viral gene flow was also obtained. Rates of nucleotide substitution were similar to those observed in a broad array of RNA viruses, and revealed a significantly higher evolutionary rate in the polymerase compared to the coat protein gene. This may reflect temperature adaptation of betanodaviruses, although a site-specific analysis of selection pressures identified relatively few selected sites in either gene. Overall, our analyses yielded novel data on the evolutionary dynamics and phylogeography of betanodaviruses and therein provides a more complete understanding of the distribution and evolution of different genotypes in Southern Europe. PMID- 22036790 TI - Airway obstruction by an aortic false aneurysm. AB - Aortic false aneurysms are rare complications of aortic valve replacement and cardiac surgical procedures in general. Aortic false aneurysms can also presents as a mediastinal mass. A false aneurysm etiology should always be considered in mediastinal mass exploration of patients with a cardiac surgery history. Although, a computed tomography (CT) scan can detect a mediastinal mass, it can equally misdiagnose an aneurysm in the absence of tumour contrast enhancement. We present the case of a 60-year-old woman who was hospitalized for a laryngeal dyspnea. She had undergone aortic valve replacement 3 years earlier and had no other relevant medical history. In the last 3 months, she presented a progressively worsening dyspnea and cough. A chest radiograph showed a large mass in the superior mediastinum. A contrast-enhanced CT-scan showed an anterior mediastinal mass (9 cm * 8 cm * 9 cm) not enhanced by contrast product, suggestive of a tissue density tumour. The mass was in fact an aortic false aneurysm where the communication with the aorta was too narrow to be filled by the contrast product in arterial phase imaging. The aneurysm was excised and successfully replaced with a prosthetic graft during deep hypothermic and circulatory arrest. In this case report, we discuss the unusual clinical presentation of this pseudoaneurysm and the absence of contrast enhancement during CT-scan, which could have lead to a catastrophic error. PMID- 22036791 TI - [Family satisfaction in intensive care unit: a prospective survey]. AB - BACKGROUND: To assess family satisfaction in the intensive care unit (ICU) and to identify parameters for improvement. STUDY DESIGN: Prospective observational monocentric study. PATIENTS AND METHODS: One hundred and twenty families were given a questionnaire of twenty-four items covering: satisfaction with reception and waiting areas, satisfaction with care and satisfaction with information/decision-making. Each item was evaluated by families according to three levels: high, intermediate, and poor satisfaction. Opinions concerning accessibility time, information notice and visitor limitations were also gathered. RESULTS: Several factors, such as waiting time, respect of family's wishes, visiting hours, lack of social support, and examination's results communication were associated with poor level of satisfaction. Twenty-three percent of families felt restricted by visitation policy for children and 17 % by visitor's number limitation. DISCUSSION: Quality of family reception in the ICU needs to be improved concerning waiting time, visiting hours, social and emotional support. PMID- 22036792 TI - Quantification of iron in the presence of calcium with dual-energy computed tomography (DECT) in an ex vivo porcine plaque model. AB - Iron deposits secondary to microbleeds often co-exist with calcium in coronary plaques. The purpose of this study was to quantify iron in the presence of calcium in an ex vivo porcine arterial plaque model using a clinical dual-energy CT (DECT) scanner. A material decomposition method to quantify the mass fractions of iron and calcium within a mixture using DECT was developed. Mixture solutions of known iron and calcium concentrations were prepared to calibrate and validate the DECT-based algorithm. Simulated plaques with co-existing iron and calcium were created by injecting the mixture solutions into the vessel wall of porcine carotid arteries and aortas. These vessel regions were harvested and scanned using a clinical DECT system and iron mass fraction was calculated for each sample. Iron- and calcium-specific staining was conducted on 5 um thick histological sections of vessel samples to confirm the co-existence of iron and calcium in the simulated plaques. The proposed algorithm accurately quantified iron and calcium amounts in mixture solutions. Maps of iron mass fraction of 60 artery segments were obtained from CT images at two energies. The sensitivity for detecting the presence of iron was 83% and the specificity was 92% using a threshold at an iron mass fraction of 0.25%. Histological analysis confirmed the co-localization of iron and calcium within the simulated plaques. Iron quantification in the presence of calcium was feasible in excised arteries at an iron mass fraction of around 1.5% or higher using current clinical DECT scanners. PMID- 22036793 TI - A longitudinal study of maternal prenatal, postnatal and concurrent depressive symptoms and adolescent well-being. AB - BACKGROUND: Maternal depression is known to be a risk for abnormal child development. Girls and boys have been found to respond differently to maternal depression. Although prenatal and postnatal depression has been widely studied, longitudinal studies of adolescent outcome are still rare. METHODS: The original sample of 349 mothers in this longitudinal study was collected in 1989-1990 in Tampere, Finland. At the latest stage, of the 327 contacted in 2006, 191 mothers and 192 adolescents aged 16 to 17 years participated in the study. Maternal depressive symptoms were screened using the Edinburgh Postnatal Depression Scale (EPDS) prenatally, postnatally and at the latest stage. Adolescent outcome was examined using the Child Behavior Checklist (CBCL) and the Youth Self Report (YSR). RESULTS: Maternal concurrent depressive symptoms were associated with adolescent behavioral and emotional problems in both genders. Maternal prenatal depressive symptoms were associated with Externalizing Problems in the YSR and boys' lower Social Competence in both the CBCL and YSR. Maternal postnatal depressive symptoms were associated with boys' lower Social Competence both in the CBCL and YSR and Externalizing Problems in the YSR. LIMITATIONS: Being a longitudinal normal population sample, the number of symptomatic mothers and adolescents is relatively small and the number of drop-outs is relatively high. Clinical evaluation of mothers and adolescents is also lacking. CONCLUSIONS: Maternal prenatal and postnatal depressive symptoms are a risk to adolescent boys' wellbeing and concurrent depressive symptoms a risk for both girls' and boys' well-being. This long-term influence should be noted when treating women with depressive symptoms throughout motherhood. PMID- 22036794 TI - Physical function as predictor for the persistence of depressive and anxiety disorders. AB - INTRODUCTION: Depressive and anxiety disorders often involve a chronic course. This study examined whether objective physical function is a predictor for the persistence of depressive and anxiety disorders. METHOD: The study sample consisted of 1206 persons with depressive and anxiety disorders at baseline. Hand grip strength and lung function were used as objective physical function measurements and were determined at baseline. Outcome variable was a 6-month depressive and/or anxiety diagnosis after 2 years of follow-up. RESULTS: Lower hand grip strength predicted the persistence of depressive and/or anxiety disorders at 2-year follow-up (per SD increase: OR=0.82, CI: 0.69-0.99, p=0.04). Associations were consistent for depressive and anxiety disorder persistence. Poorer lung function was associated with the persistence of depressive disorders (per SD increase: OR=0.83, CI: 0.70-0.98, p=0.03) but not with anxiety disorders. LIMITATIONS: Follow-up was limited to 2 years. CONCLUSIONS: Objectively measured poorer physical function predicted the persistence of depressive and/or anxiety disorders. PMID- 22036795 TI - AMPA receptor expression is increased post-mortem samples of the anterior cingulate from subjects with major depressive disorder. AB - BACKGROUND: Glutamate is thought to be involved in the pathophysiology of major depressive disorder and bipolar disorder; however, the molecular changes underlying abnormal glutamatergic signalling remain poorly understood. Whilst previous studies have suggested that the NMDA receptor may be involved in the pathophysiology of mood disorders, it is unclear whether the non-NMDA receptors are also involved. Therefore, we sought to examine whether the expression of the non-NMDA, ionotropic glutamate receptors, AMPA receptor and kainate receptor, is altered in mood disorders. METHODS: We used [3H]AMPA and [3H]kainate to measure the levels of AMPA and kainate receptor, respectively, in the anterior cingulate (BA 24) and dorsolateral prefrontal cortex (BA 46) from post-mortem CNS in 10 subjects with major depressive disorder, 10 subjects with bipolar disorder and 10 control subjects. RESULTS: A 20.7% to 27.7% increase in [3H]AMPA binding density was seen in BA 24 (p<0.05) but not BA 46 (p>0.05) in major depressive disorder compared to control levels. [3H]AMPA binding density was not changed in bipolar disorder in either BA 24 or BA 46 (p>0.05) compared to controls. [3H]Kainate binding was not changed in either BA 24 or BA 46 in either disorder compared to controls (p>0.05). LIMITATIONS: Small sample sizes (n=10) were used in this study. The subjects were not drug naive. CONCLUSIONS: Our data suggests increased in AMPA receptor levels in the anterior cingulate are involved in the pathophysiology of major depressive disorder. This data has relevance for the development of new anti-depressant drugs targeted towards the AMPA receptors. PMID- 22036796 TI - The I/D polymorphism of angiotensin-converting enzyme gene in major depressive disorder and therapeutic outcome: a case-control study and meta-analysis. AB - BACKGROUND: The insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene has been implicated in susceptibility to major depressive disorder (MDD) and its treatment response; however, a large number of studies have reported inconsistent results. The aim of this study is to examine the role of I/D polymorphism of ACE gene in MDD risk and its treatment response by a case control study and meta-analysis. METHODS: Three hundred and sixty eight depressed patients who met DSM-IV criteria for major depressive disorder and 371 normal controls were recruited for the study. We searched Pubmed, Embase, CNKI, Wanfang, and Weipu database, covering all papers until March 31, 2011. Statistical analysis was performed using the software STATA 10.0. RESULTS: Genotype and allele distributions of ACE I/D were not significantly different between case and control groups. No significant association with treatment response was discovered. A total of 2479 cases and 7744 controls in 15 case-control studies were included in this meta-analysis. The results indicated that the D/D homozygote carriers had an 18% increased risk of MDD, when compared with the homozygotes I/I and heterozygote I/D [odds ratio (OR)=1.18, 95% confidence interval (CI):1.04-1.33]. In the subgroup analysis, significant elevated risks were associated with D/D homozygote carriers in Caucasians (OR=1.20 and 95% CI: 1.04-1.38 for D/D vs I/D+I/I) but not in Asians. Moderate trends of an increased risk in the D allele carriers from total sample (OR, 1.15; 95% CI: 1.02-1.30) was also observed. The D/D homozygote carriers were associated with a 28% increased risk of MDD relative to the homozygotes I/I (OR 1.28; 95% CI: 1.11-1.49). In subgroup analysis, Caucasians showed significant association (OR 1.30; 95% CI: 1.09-1.56). No association was found in the Asian groups. No publication bias was observed in this meta-analysis by using the Egger method. CONCLUSIONS: The ACE I/D polymorphism is not associated with MDD and its treatment response in a Chinese case-control study. Meta-analysis evidence suggests that the I/D polymorphism of ACE gene may be a risk factor of major depressive disorder in Caucasians. PMID- 22036797 TI - Protein levels of beta-catenin and activation state of glycogen synthase kinase 3beta in major depression. A study with postmortem prefrontal cortex. AB - BACKGROUND: The Wnt/GSK3beta signaling pathway was implicated in mood disorders. Beta-catenin is a protein targeted by this signaling axis. We aimed to examine whether there is an abnormality in this signaling axis in major depression. METHODS: Postmortem brains from 20 depressed and 20 non-depressed subjects were used. In both groups, suicide and non-suicide were included in equal number. Protein levels of beta-catenin, tGSK3beta and ser(9)-pGSK3beta were determined in prefrontal cortex. RESULTS: ANOVA yielded significant variations between groups in beta-catenin (F(3,36)=19.5; p<0.001) and pGSK3beta protein (F(3,36)=14.3; p<0.001) and in tGSK3beta-to-pGSK3beta ratio (F(3,36)=10.9; p<0.001). Fisher tests showed decrease in both groups of MDD and MDD with suicide (MDD+S) for beta catenin (p<0.001) and pGSK3beta levels (p<0.001) respectively. The tGSK3beta-to pGSK3beta ratio was increased in MDD and MDD+S subjects (p<0.001). A negative correlation was observed between beta-catenin levels and the activation state of the GSK3beta (r2=0.358; p<0.005). LIMITATIONS: The sample was small and only a fraction of s(9)-pGSK3beta, albeit significant, was used and; the mood state at the time of death was unknown. CONCLUSIONS: The study observed a dysregulation of Wnt/GSK3beta signaling associated with a lifetime of major depression. The study may have relevance in further development of drugs based on GSK3beta inhibition. PMID- 22036798 TI - The railway suicide death of a famous German football player: impact on the subsequent frequency of railway suicide acts in Germany. AB - BACKGROUND: The railway suicide of Robert Enke, an internationally respected German football goal keeper, sent shockwaves throughout the world of football. We analyzed its impact on the frequency of subsequent railway suicide acts (RS). METHODS: Two analytic approaches were performed applying German Railway Event database Safety (EDS) data: first, an inter-year approach comparing the incidence of RS during a predefined "index period" with identical time windows in 2006 to 2008; second, an intra-year approach comparing the number of RS 28 days before and after the incidence. To analyze a possible "compensatory deficit", the number of RS in the subsequent first quarter of 2010 was compared with the identical time windows in the preceding three years. Incidence ratios with 95% confidence intervals were estimated by Poisson regression. Findings were controlled for temperature. FINDINGS: Compared to the preceding three years, the incidence ratio (IR) of the number of RS in the index period increased by 1.81 (1.48-2.21; p<0.001), leading to an overall percentage change of 81% (48-121%; p<0.001). Comparing the number of suicides 28 days before and after the incidence revealed an even more pronounced increase of IR (2.2; 1.6-3.0). No modifications of these associations were observed by daytime, by location of the suicide and fatality. No compensatory deficit occurred in the post-acute period. INTERPRETATION: The substantial increase of RS in the aftermath of the footballer's suicide death brought about copycat behavior in an unforeseen amount, even though the media reporting was largely sensitive and preventive measures were taken. PMID- 22036799 TI - Depression: point-prevalence and sociodemographic correlates in a Buenos Aires community sample. AB - BACKGROUND: Since the current epidemiology of depression is not well documented in Latin America, we conducted a community-based survey study in Argentina. METHODS: The Beck Depression Inventory (BDI) and a general health questionnaire were completed by 1335 adult participants, representing most of the neighborhoods of Buenos Aires. RESULTS: Prevalence of high total BDI scores (>=13) indicating probable current clinically significant depression was 20.0% (women: 20.6%; men: 19.6%). Probable depression was associated with being unmarried and older, less educated, reporting recent stressors and significant medical illness. LIMITATIONS: Sampling was cross-sectional and by convenience; probable depression was not verified by clinical assessment. CONCLUSIONS: Within methodological limits, probable current clinically significant depression was highly prevalent in an urban community sample in Argentina, at rates and with risk factors similar to those found in other world regions. PMID- 22036800 TI - The psychological costs and benefits of being highly persistent: personality profiles distinguish mood disorders from anxiety disorders. AB - BACKGROUND: The personality trait of Persistence is highly valued by conscientious overachievers, but it has both psychological costs and benefits. The interactions among multiple personality factors influencing the development of mood and anxiety disorders have been confounded in prior clinical samples, but can be disentangled in terms of their underlying brain circuitry and influence on perception of emotional stimuli. METHODS: 285 individuals who represented the full range of personality variation in a large sample of adult volunteers from the general community of Israel were selected for follow-up by psychiatric interviews, cognitive testing, and medical examinations. The Temperament and Character Inventory (TCI) measured profiles of traits that distinguished individuals with diagnoses of mood and/or anxiety disorders using linear discriminant analysis and non-linear profile analysis. RESULTS: High Harm Avoidance and low Self-directedness strongly distinguished people with mood and/or anxiety disorders from those with neither. High Persistence distinguished people with only anxiety disorders from those with mood disorders. High Persistence was associated with greater health and happiness overall, but also led to more negative emotions than in people with low Persistence unless they were both unusually tolerant of frustration (i.e., low in Harm Avoidance) and self-accepting of personal limitations (i.e. high in Self-directedness). LIMITATIONS: Subjects were volunteers over 40 years of age at assessment. CONCLUSIONS: People who are highly persistent (i.e., persevering, ambitious, perfectionistic) are more likely to have anxiety disorders than mood disorders, even when they have other traits increasing risk for both (i.e., high Harm Avoidance and low Self-directedness). High Persistence increases both positive and negative emotions in most people. However, high Persistence reduces negative emotions and increases positive emotions if a person is easy-going (i.e., "happy go-lucky" when low in both Harm Avoidance and Self-directedness). PMID- 22036802 TI - Predictors of relapse or recurrence in bipolar I disorder. AB - OBJECTIVES: Bipolar disorder represents a major public health concern and, despite treatment, is characterized by recurring episodes of mania, depression, or mixed states. Prevention of relapse or recurrence is a primary treatment objective in the management of the disorder. The objective of the current study was to identify predictors of relapse/recurrence in patients with bipolar I disorder treated with olanzapine, lithium, divalproex, or olanzapine plus divalproex/lithium. METHODS: Data from four clinical trials studying the efficacy of olanzapine compared to placebo and active comparators (lithium, divalproex, olanzapine plus divalproex/lithium) for bipolar I disorder were pooled for this analysis. Patients achieving remission after pharmacological treatment and entering randomized double-blind maintenance phase for 44 to 72 weeks were included. Cox Proportional Hazard models and Kaplan-Meier analyses were used to determine predictors of relapse/recurrence for the pooled data and within each treatment group. RESULTS: A total of 929 patients meeting the criteria for remission and followed by maintenance treatment were included in this analysis, and 427 patients (46.0%) experienced symptomatic relapse/recurrence during the follow-up period. A 21-item Hamilton Depression Rating Scale (HAMD-21) total score<4, gender, rapid cycling and treatment emerged as significant predictors of relapse/recurrence and may be generalized to treatment with olanzapine and to some extent to treatment with lithium and divalproex. The results on treatment specific predictors of relapse/recurrence are considered to be exploratory and no adjustments were made for multiple comparisons. CONCLUSION: The major findings from this study suggest that a HAMD-21 total score<4 may be a better predictor of maintenance of remission in bipolar I patients than HAMD-21 total score<8. The prophylactic effect of olanzapine, lithium, divalproex, olanzapine plus divalproex or lithium, and placebo was assessed and baseline predictors of relapse/recurrence were identified. PMID- 22036801 TI - Remitted major depression is characterized by reward network hyperactivation during reward anticipation and hypoactivation during reward outcomes. AB - BACKGROUND: Although functional brain imaging has established that individuals with unipolar major depressive disorder (MDD) are characterized by frontostriatal dysfunction during reward processing, no research to date has examined the chronometry of neural responses to rewards in euthymic individuals with a history of MDD. METHOD: A monetary incentive delay task was used during fMRI scanning to assess neural responses in frontostriatal reward regions during reward anticipation and outcomes in 19 participants with remitted major depressive disorder (rMDD) and in 19 matched control participants. RESULTS: During the anticipation phase of the task, the rMDD group was characterized by relatively greater activation in bilateral anterior cingulate gyrus, in right midfrontal gyrus, and in the right cerebellum. During the outcome phase of the task, the rMDD group was characterized by relatively decreased activation in bilateral orbital frontal cortex, right frontal pole, left insular cortex, and left thalamus. Exploratory analyses indicated that activation within a right frontal pole cluster that differentiated groups during reward anticipation predicted the number of lifetime depressive episodes within the rMDD group. LIMITATIONS: Replication with larger samples is needed. CONCLUSIONS: Results suggest a double dissociation between reward network reactivity and temporal phase of the reward response in rMDD, such that rMDD is generally characterized by reward network hyperactivation during reward anticipation and reward network hypoactivation during reward outcomes. More broadly, these data suggest that aberrant frontostriatal response to rewards may potentially represent a trait marker for MDD, though future research is needed to evaluate the prospective utility of this functional neural endophenotype as a marker of MDD risk. PMID- 22036803 TI - Proximal isovelocity surface area variability during systole in dogs with mitral valve prolapse. AB - The proximal isovelocity surface area (PISA) principles and methodology have been described in human and veterinary medicine with special emphasis given to the ease and speed for the quantification of mitral regurgitation. Although limitations have been described in both human and veterinary medicine, in the case of veterinary medicine, clinical examples have not been well defined and in some cases have not been individually presented. The objective of this paper is to illustrate in a qualitative manner the echocardiographic existence of the dynamic behavior and variability of mitral regurgitation in dogs with mitral valve prolapse, a factor to be taken into consideration as a limitation inherent to the PISA technique. PMID- 22036804 TI - External-beam radiation therapy should be given with androgen deprivation treatment for intermediate-risk prostate cancer: new confirmatory evidence. PMID- 22036806 TI - Cytoplasmic p27Kip1 counteracts the pro-apoptotic function of the open conformation of PTEN by retention and destabilization of PTEN outside of the nucleus. AB - The tumor suppressor activity of p27Kip1 takes place in the cell nucleus by inhibitory binding to cyclin/CDK complexes. p27Kip1 can also be localized in the cytoplasm, where it has been proposed to have oncogenic properties. Here, we describe a novel role for cytoplasmic p27Kip1 which could account for its activity as an oncoprotein by negative regulation of the PTEN tumor suppressor. p27Kip1 physically interacted with the open conformation of PTEN, which is competent to enter the nucleus. In mammalian cells, cytoplasmic p27Kip1 retained to nuclear-targeted PTEN in the cytoplasm. This retention was exerted by the C terminal p27Kip1 region, and was independent of cyclin/CDK-binding. The nuclear accumulation of PTEN triggered by pro-apoptotic TNFalpha treatment was abolished by cytoplasmic p27Kip1. Furthermore, conformationally-open PTEN displayed diminished protein stability and pro-apoptotic activity in the presence of cytoplasmic p27Kip1. Our results support a conformationally-dependent model of cytoplasmic retention and negative regulation of the activity of nuclear PTEN by oncogenic cytoplasmic p27Kip1, and suggest the existence of reciprocal mechanisms to regulate the levels of both p27Kip1 and PTEN. PMID- 22036805 TI - The putative tumor suppressor Zc3h12d modulates toll-like receptor signaling in macrophages. AB - Toll-like receptors (TLR) are pivotal in macrophage activation. The molecular mechanisms controlling TLR signaling and macrophage activation are not completely understood. Zc3h12d is originally identified as a possible tumor suppressor gene. However, its function remains unknown. We here report that Zc3h12d negatively regulates TLR signaling and macrophage activation. Zc3h12d was enriched in spleen, lung and lymph node. In macrophages, the expression of Zc3h12d was remarkably induced by TLR ligands through JNK and NF-kappaB signal pathways. On the other hand, overexpression of Zc3h12d significantly inhibited TLR2 and TLR4 activation-induced JNK, ERK and NF-kappaB signaling as well as macrophage inflammation. Similar to Zc3h12a/MCPIP1, Zc3h12d also decreased the global cellular protein ubiquitination. These findings suggest that Zc3h12d is a novel negative feedback regulator of TLR signaling and macrophage activation and thus may play a role in host immunity and inflammatory diseases. PMID- 22036807 TI - Endothelial protein C receptor 1651C/G polymorphism and soluble endothelial protein C receptor levels in women with idiopathic recurrent miscarriage. AB - High levels of soluble endothelial protein C receptor (EPCR) induce coagulation dysfunction by inhibiting protein C activation, and activated protein C (APC) activity. We tested whether EPCR 1651C/G promoter variant and changes in plasma soluble EPCR levels are risk factors for idiopathic recurrent spontaneous miscarriage (RSM). A case-control study involving 283 RSM cases and 380 age and BMI-matched control women. EPCR 1651C/G genotyping was performed by PCR-RFLP method. Plasma-soluble EPCR levels were measured with ELISA. The 1651G allele frequency and C/G genotype were significantly higher in RSM cases than controls; none of the cases or control participants was a 1651G/G homozygote. Lower soluble EPCR levels were seen in RSM cases compared to controls, and higher soluble EPCR levels were seen in 1651C/G compared to 1651C/C carriers in cases and controls. Lower soluble EPCR levels were seen in cases, both in 1651C/C (P = 0.0046) and 1651C/G (P = 0.0032) genotype carriers. Multivariate analysis demonstrated strong association of EPCR 1651C/G [P = 0.011; adjusted odds ratio (aOR) (95% confidence interval [CI] = 3.13 (1.31-7.60)], but not soluble EPCR plasma levels [P = 0.067; aOR (95% CI) = 1.01 (1.00-1.10)], with increased RSM risk. In addition, smoking was independently associated with increased RSM risk [P = 0.002; aOR (95% CI) = 2.86 (1.48-5.52)]. EPCR 1651C/G polymorphism and elevated soluble EPCR levels but low soluble EPCR levels increase the risk of idiopathic RSM. Replication studies on other racial groups, and other EPCR gene variants, are warranted. PMID- 22036808 TI - Thrombomodulin as a regulator of the anticoagulant pathway: implication in the development of thrombosis. AB - Thrombomodulin is a cell surface-expressed glycoprotein that serves as a cofactor for thrombin-mediated activation of protein C (PC), an event further amplified by the endothelial cell PC receptor. The PC pathway is a major anticoagulant mechanism that downregulates thrombin formation and hedges thrombus formation. The objectives of this review were to review recent findings regarding thrombomodulin structure, its involvement in the regulation of hemostasis and further discuss the implication, if any, of the genetic polymorphisms in the thrombomodulin gene in the risk of development of thrombosis. We performed a literature search by using electronic bibliographic databases. Although the direct evaluation of risk situations associated with thrombomodulin mutations/polymorphisms could be of clinical significance, it appears that mutations that affect the function of thrombomodulin are rarely associated with venous thromboembolism. However, several polymorphisms are reported to be associated with increased risk for arterial thrombosis. Additionally studies on knock out mice as well studies on humans bearing rare mutations suggest that thrombomodulin dysfunction may be implicated in the pathogenesis of myocardial infraction. PMID- 22036809 TI - Positive and negative Coulomb drag in vertically integrated one-dimensional quantum wires. AB - Electron interactions in and between wires become increasingly complex and important as circuits are scaled to nanometre sizes, or use reduced-dimensional conductors such as carbon nanotubes, nanowires and gated high-mobility two dimensional electron systems. This is because the screening of the long-range Coulomb potential of individual carriers is weakened in these systems, which can lead to phenomena such as Coulomb drag, where a current in one wire induces a voltage in a second wire through Coulomb interactions alone. Previous experiments have demonstrated Coulomb electron drag in wires separated by a soft electrostatic barrier of width ?80 nm (ref. 12), which was interpreted as resulting entirely from momentum transfer. Here, we measure both positive and negative drag between adjacent vertical quantum wires that are separated by ~15 nm and have independent contacts, which allows their electron densities to be tuned independently. We map out the drag signal versus the number of electron sub bands occupied in each wire, and interpret the results both in terms of momentum transfer and charge-fluctuation induced transport models. For wires of significantly different sub-band occupancies, the positive drag effect can be as large as 25%. PMID- 22036810 TI - Nanoelectronics: a closer look at charge drag. PMID- 22036811 TI - Electric-field-induced wetting and dewetting in single hydrophobic nanopores. AB - The behaviour of water in nanopores is very different from that of bulk water. Close to hydrophobic surfaces, the water density has been found to be lower than in the bulk, and if confined in a sufficiently narrow hydrophobic nanopore, water can spontaneously evaporate. Molecular dynamics simulations have suggested that a nanopore can be switched between dry and wet states by applying an electric potential across the nanopore membrane. Nanopores with hydrophobic walls could therefore create a gate system for water, and also for ionic and neutral species. Here, we show that single hydrophobic nanopores can undergo reversible wetting and dewetting due to condensation and evaporation of water inside the pores. The reversible process is observed as fluctuations between conducting and non conducting ionic states and can be regulated by a transmembrane electric potential. PMID- 22036812 TI - The communication challenges presented by nanofoods. PMID- 22036813 TI - Mixing subattolitre volumes in a quantitative and highly parallel manner with soft matter nanofluidics. AB - Handling and mixing ultrasmall volumes of reactants in parallel can increase the throughput and complexity of screening assays while simultaneously reducing reagent consumption. Microfabricated silicon and plastic can provide reliable fluidic devices, but cannot typically handle total volumes smaller than ~1 * 10( 12) l. Self-assembled soft matter nanocontainers can in principle significantly improve miniaturization and biocompatibility, but exploiting their full potential is a challenge due to their small dimensions. Here, we show that small unilamellar lipid vesicles can be used to mix volumes as small as 1 * 10(-19) l in a reproducible and highly parallelized fashion. The self-enclosed nanoreactors are functionalized with lipids of opposite charge to achieve reliable fusion. Single vesicles encapsulating one set of reactants are immobilized on a glass surface and then fused with diffusing vesicles of opposite charge that carry a complementary set of reactants. We find that ~85% of the ~1 * 10(6) cm(-2) surface-tethered nanoreactors undergo non-deterministic fusion, which is leakage free in all cases, and the system allows up to three to four consecutive mixing events per nanoreactor. PMID- 22036814 TI - [Stereotactic and functional neurosurgery: frame-based and frameless]. PMID- 22036815 TI - [Prolactinoma treatment status in the cabergoline era]. AB - The aim of our study is to report the most adequate therapy for prolactinoma in the cabergoline era. From 2003 to 2009, 27 patients with prolactinoma were treated at our hospital. Patients are categorized into 2 groups. The Cabergoline Group: Cabergoline was administered for 5 years and discontinued. Using this protocol, the case with normal prolactin level in addition to having no visible tumor more than 24 months after the discontinuation of cabergoline was judged as cured. The Operation Group: Transsphenoidal surgery (TSS) was performed first. In the Cabergoline group, 12 cases were cured with 5 years cabergoline treatment (Cure) and 6 cases were not cured (Not cure). We compared the pretreatment prolactin level, the normalization of the serum level of prolactin, the degree of invasiveness on MRI, regression of the tumor during treatment on MRI, max dose of cabergoline, degree of pituitary hormone replacement, frequency of pregnancy, and follow up periods between the Cabergoline-cure group, the Cabergoline-not-cure group, and the Operation group. Normalization rate in serum level of prolactin and cure rate were 91% and 63% in the Cabergoline group. Pretreatment prolactine level and the frequency of tumor invasiveness on initial MRI were significantly higher in the Cabergoline-not-cure group compared to the Cabergoline-cure group. All of the five woman accompanied with pregnancy after the treatment belonged to the Cabergoline-cure group. In the Operation group, all 4 cases achieved normalization of serum prolactin level without visible tumor and with normal pituitary function. Cabergoline for prolactinoma is effective, but the cure rate by continuous usage of cabergoline for 5 years was 67%. The factors that cabergoline and / or TSS can cure prolactinoma are non-invasive tumor and prolactin level under 200 ng/mL at pretreatment. PMID- 22036816 TI - [Relationship between living arrangements and stroke in Sano-Kosei General Hospital]. AB - We retrospectively reviewed the relationship between living arrangements and stroke in Sano-Kosei General Hospital, for the 3-year period from December, 2007 to November, 2010. The proportion of live-alone among stroke patients was 14.9% (131/877). The indirect standardized live-alone ratio (95% confidence interval), compared with Sano city's live-alone ratio as a standard group, was 1.34 (1.13 1.60). Among live-alone patients with stroke, sex ratio showed no significant difference (p=0.46). Comparing live-alones with non-live-alones in stroke patients, the mean age of live-alones was younger for men, but older for women (p<0.001). There was no significant difference between living arrangements and diseases risk factors. However, on the point of the mean number of risk factors, live-alones tended to have more risk factors than non-live-alones (p=0.032). Therefore, living arrangements are considered as an important factor for prevention of stroke. PMID- 22036817 TI - [Peritoneal catheter placement into the suprahepatic space: a report of 2 cases with abdominal complications of ventriculoperitoneal shunts]. AB - Complications arising from the placement of ventriculoperitoneal shunts are common. These complications may be related to a number of causes and present with various symptoms. Of these, abdominal complications such as formation of intraperitoneal pseudocysts and abdominal abscesses possibly recur, but, alternative sites for placing the peritoneal catheter of ventriculoperitoneal shunts are limited. We present two cases of ventriculoperitoneal shunt malfunctioning due to repeated abdominal complications. The location of the peritoneal end of the shunt was successfully revised to the suprahepatic space in the peritoneal cavity. We describe the clinical course of these two cases in this report, along with a precise technique of placing the peritoneal end of the shunt into the suprahepatic space. In addition, we will discuss the validity of this space as an alternative site for the placement of the peritoneal end of the ventriculoperitoneal shunt. PMID- 22036818 TI - [Deep sylvian meningioma without dural attachment: a case report]. AB - A 34-year-old female presented with an 8-year history of temporal lobe epilepsy. Magnetic resonance imaging showed a multilobular, well-demarcated and homogeneous tumorous lesion of 5 cm in diameter deep in the left sylvian fissure. Intraoperative findings revealed that the tumor was mainly in the left insular region without dural attachment and strongly adhered to the left middle cerebral artery and its perforators. The histopathological diagnosis was transitional meningioma without malignancy. There are few reported cases of deep sylvian meningioma without dural attachment. We review the literature and summarize the clinicopathological characteristics of this condition. PMID- 22036819 TI - [A case of medullomyoblastoma]. AB - Medullomyoblastoma is a rare histologic variant of medulloblastoma. We report a case of medullomyoblastoma occurring in the cerebellar vermis. A 12-year-old girl presented with a 3-month history of headache, nausea, vomiting and unsteadiness of gait. Magnetic resonance imaging (MRI) revealed a mass lesion in the cerebellar vermis. A suboccipital craniectomy was perfomed to remove a tumor. Immunohistochemical studies confirmed the presence of both a primitive neuroectodermal component and rhabdomyoblastic differentiation, consistent with the diagnosis of medullomyoblastoma. PMID- 22036820 TI - [A successful treatment for a case of idiopathic syringomyelia with syrinx located in the anterior horn]. AB - Idiopathic syringomyelia not associated with Chiari malformation, tumor, nor tetherd cord syndrome has not been frequently reported. So the clinical significance and optimum treatment strategy for this disease remains unclear. We report a 37-year-old man who was diagnosed as having idiopathic syringomyelia and was treated successfully using implantation of a syringo-subarachnoid shunt. The patient suffered gradual worsening of sensory disturbance in the upper extremities, and Magnetic resonance imaging demonstrated a large syrinx located in the cervical spinal cord (C2-3), located mainly at the left anterior horn. We performed syringo-subarachnoid shunt for syringomyelia under partial hemilaminectomy. During the surgery, the spinal cord was markedly rotated and dorsal root entry had shifted to the midline because of the large syrinx. In order to perform myelotomy at the dorsal root entry zone, we needed additional drilling to the medial portion of the lamina. After this procedure, we were able to perform implantation of the syringo-subarachnoid shunt safely. After the operation, the syrinx collapsed immediately and no neurological deficit was observed. The patient was discharged 2 weeks after the operation. Idiopathic syringomyelia in which the syrinx has deviated to the anterior horn is rare. In those cases, we consider that sufficient hemilaminectomy for the midline should be performed. PMID- 22036821 TI - [Successful microvascular decompression of the medulla oblongata for a case with respiratory failure: case report]. AB - We report a case of the medulla oblongata syndrome successfully treated by microvascular decompression surgery. The patient was a 75-year-old woman and had been suffering from gradual progressive dyspnea since July, 2009. Two month later, intubation and medial ventilator treatments were began because of severe respiratory problems. The central respiratory problems were considered in extensive testing by the physician. The head MR imaging showed that the left vertebral artery had markedly compressed the medulla oblongata. We thought that her respiratory problems were associated with this vertebral artery compression of the medulla oblongata. We performed the microvascular decompression surgery by left trans-condylar fossa approach. Her hypoventilation graduately improved after the surgery and she needed neither ventilator nor oxygen in several months. She is able to perform daily activities by herself. We report the case, and discuss the cause of respiratory problems especially by compression of the medulla oblongata. PMID- 22036822 TI - [Intracerebral xanthogranuloma with specific MRI features: a case report]. AB - We report a case of a 47-year-old male who had a left frontal lobe mass with specific magnetic resonance imaging (MRI). Four years previous to his admission to our hospital, he developed acute myelocytic leukemia and he was implanted with peripheral blood stem cell transplantation. One month before his admission, he was unable to walk due to right leg motor weakness. MRI revealed a round mass lesion at the left frontal lobe. Initial diagnosis was a brain abscess, so he was administered some antibacterial drug. However, his neurological symptoms kept getting worse with increase of mass size on MRI. T1-weighted MR images showed the mass as a low intensity lesion with incomplete ring-like Gd-enhancement. T2 weighted images showed the mass as a high intensity lesion with many linear shadows inside the mass. Diffusion weighted images showed the mass as a low intensity lesion. MR spectroscopy revealed an elevation of choline and lactate peak. Differential diagnosis was glioma or demyelinating disease. At the operation, the mass was light yellow and seen to be rich with vessels. The pathological diagnosis was xanthogranuloma in the brain. Postoperative course was uneventful. The frontal residual mass lesion decreased in size and Gd enhancement. PMID- 22036823 TI - [A case of hemifacial spasm in a juglar foramen tumor patient treated by microvascular decompression]. AB - Hemifacial spasm is a movement disorder characterized by involuntary paroxysmal chronic contractions of the facial musculature. The usual cause is simple vascular compression of the facial nerve, at its root exit zone of the brain stem. Previously only a case of hemifacial spasm associated with a juglar foramen tumor has been reported in the literature. In this article, we report a case in which hemifacial spasm accompanied an ipsilateral juglar foramen tumor in a 62 year-old woman. The sole use of arterial decompression of the facial nerve at the root exit zone resulted in complete resolution of the patient's symptoms. PMID- 22036824 TI - [Congenital anomalies in the central nervous system(12) arachnoid cyst]. PMID- 22036825 TI - Thromboprophylaxis in carriers of antiphospholipid antibodies (APL) without previous thrombosis: "Pros" and "Cons". AB - The presence of anti-phospholipid (aPL) is necessary but not sufficient to induce a thrombotic event. The "second hit" hypothesis suggested that an additional trigger may be needed to develop a vascular event in aPL carriers. In this article, pro and con of primary thromboprophylaxis in aPL carriers is deeply discussed, concluding that univocal data are not available, due to conflicting results of available clinical trials. However, in clinical practice the primary thromboprophylaxis is not indicated in all unselected asymptomatic aPL carriers, and the best strategy begin with the assessment of the peculiar risk profile of the subject. Thus, it is mandatory to eliminate modifiable prothrombotic risk factors (i.e. smoking, oral contraceptive), to treat the irreversible risk factors (i.e. hypertension, diabetes) and to introduce an aggressive prophylaxis with subcutaneous LMWH in high-risk situations (i.e. surgical procedures with prolonged immobilization). A different evaluation should be addressed to aPL carriers with a concomitant autoimmune disease that are considered as an additional pro-thrombotic risk factor. Similarly, concomitant positivity for more than one anti-phospholipid test confer a stronger risk of developing the thrombotic manifestations. Specific trials with larger cohorts of patients are needed to better clarify this issue. PMID- 22036826 TI - Is fibromyalgia a discrete entity? AB - Fibromyalgia (FM) is defined as chronic widespread pain (CWP) with allodynia or hyperalgesia to pressure pain, and is classified as one of the largest group of soft tissue pain syndromes. Its pathogenesis is not entirely understood, although it is currently believed to be the result of a central nervous system (CNS) malfunction that increases pain transmission and perception. There are no instrumental tests to confirm the diagnosis, but many of the differential diagnoses can be excluded by means of an extensive clinical examination and patient history. Although fibromyalgia is a recognisable clinical entity, it would seem appropriate to consider the entire range of tenderness and distress in clinic patients in order to tailor treatment on an individual basis. PMID- 22036827 TI - High intensity anticoagulation in the prevention of the recurrence of arterial thrombosis in antiphospholipid syndrome: 'PROS' and 'CONS'. AB - The use of high intensity anticoagulation in the prevention of recurrence of arterial thrombosis related to the Antiphospholipid Syndrome (APS) is still controversial. This paper reports a debate that took place at the CORA meeting (Controversies in Rheumatology and Autoimmunity), held in Florence in March 2011. Major points of discussion were: 1) the paucity of prospective randomized clinical trials; retrospective studies were the main source supporting the use of high intensity anticoagulation; 2) heterogeneity in antiphospholipid antibodies (aPL) definition, due to the lack of standardization of aPL assays and to the failure to distinguish patients with a high risk profile ("triple positive") from those a low risk profile; 3) bleeding is a major concern about high intensity anticoagulation; however, studies are not concordant in reporting an increased risk compared to the standard regimen; 4) practical issues consist of difficulties in keeping a stable PT-INR over 3 and the possibility for interference by aPL on the thromboplastins used for PT-INR measurement. In conclusion, there is currently a lack of consensus on the use of high intensity anticoagulation for the secondary prophylaxis of arterial thrombosis. However, such a treatment may be particularly recommended in those APS patients who have a high risk aPL profile and other concomitant cardiovascular risk factors, provided that the potential benefit outweighs the risk of bleeding. PMID- 22036828 TI - Macrophages and neutrophils in SLE-An online molecular catalog. AB - Systemic Lupus Erythematosus (SLE) is a heterogeneous group of autoimmune disorders defined by a consensus of clinical and laboratory criteria. Much of the pathophysiology and therapy of SLE has focused on autoimmune B and T cells of the adaptive immune system. Recently, focus has shifted to the role of myeloid cells like neutrophils and macrophages - part of the innate immune system - in SLE pathogenesis. These cells have altered molecular profiles affecting multiple pathways, but no salient overview has been undertaken to broadly define and categorize this dysregualtion. Here we endeavor to provide this overview and build a new freely accessible online resource for this purpose (http://www.mohanlab.org/SLE_BASE/myeloid_cells/). PMID- 22036829 TI - Rituximab - shadow, illusion or light? AB - Rituximab (Rituxan, Mabthera) is a monoclonal therapeutic anti-CD20 antibody approved for use in lymphoma and rheumatoid arthritis but not for use in systemic lupus erythematosus (SLE). Nonetheless, over the past decade many reports based on case series and observational studies have suggested benefits in selected groups of SLE patients with this monoclonal. It is also clear that off-label use of rituximab in SLE is not uncommon in many countries in the world. However, two randomized controlled clinical trials of rituximab failed to demonstrate a benefit for this agent, raising important questions on how to assess the potential role of rituximab in SLE. In this article I will review the available data and provide some comments that may be of use for the practicing clinician. PMID- 22036830 TI - Does seronegative antiphospholipid syndrome really exist? AB - The diagnosis of seronegative (SN-) antiphospholipid syndrome (APS) has been suggested for patients with clinical manifestations indicative of APS but with persistently negative results in the commonly used assays to detect anti cardiolipin (aCL) antibodies, anti-beta2 Glycoprotein I antibodies (abeta2GPI), and lupus anticoagulant (LA). To date the best management of these patients is still unclear. New emerging anti-phospholipid (aPL) assays could improve our ability in diagnosing APS. However, the availability of aPL assays in routine laboratory practice is limited. In fact, even abeta2GPI is routinely tested in only a small number of laboratories, and other aPL, such as anti-prothrombin or anti-annexin antibodies, in only a few research laboratories. On the other hand transient or false negative aPL assay and other genetic or acquired pro thrombotic conditions can further complicate this issue. This paper is focused on the arguments for and against the diagnosis of SN-APS and is aimed to help the clinician when approaching a patient with clinical manifestations consistent with APS diagnosis but with negative aPL using the commonly available tests. PMID- 22036831 TI - Separating predictable and unpredictable work to manage interruptions and promote safe and effective work flow. AB - Predictable and unpredictable patient care tasks compete for caregiver time and attention, making it difficult for patient care staff to reliably and consistently meet patient needs. We have piloted a redesigned care model that separates the work of patient care technicians based on task predictability and creates role specificity. This care model shows promise in improving the ability of staff to reliably complete tasks in a more consistent and timely manner. PMID- 22036832 TI - Effectiveness of 2 methods of chlorhexidine bathing. AB - The purposes of this study were to examine the impact of chlorhexidine on the transmission of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus (VRE) on an inpatient oncology unit, compare the cost of 2 chlorhexidine bath delivery methods, and evaluate nursing time and satisfaction to administer the baths. MRSA and VRE transmission rates decreased from those during the previous years. Costs associated with bathing increased, but time to administer the bath decreased with the chlorhexidine cloths, and nursing staff reported satisfaction with their use. PMID- 22036833 TI - Uncovering the intimate relationship between lipids, cholesterol and GPCR activation. AB - The membrane bilayer has a significant influence over the proteins embedded within it. G protein-coupled receptors (GPCRs) form a large group of membrane proteins with a vast array of critical functions, and direct and indirect interactions with the bilayer are thought to control various essential aspects of receptor function. The presence of cholesterol, in particular, has been the focus of a number of recent studies, with varying receptor-dependent effects reported. However, the possibility of specific cholesterol binding sites on GPCRs remains debatable at present. A deeper structural and mechanistic understanding of the complex and delicately balanced nature of GPCR-bilayer interactions has only been revealed so far in studies with the non-ligand binding, class A GPCR, rhodopsin. Further investigations are essential if we are to appreciate fully the role of the bilayer composition in GPCR activation and signalling; indeed, recent improvements in GPCR expression and purification, along with development of novel reconstitution methods should make these types of biophysical investigations much more accessible. In this review we highlight the latest research on GPCR-membrane interactions and some of the tools available for more detailed studies. PMID- 22036834 TI - Porcine circovirus: transcription and DNA replication. AB - This review summarizes the molecular studies pertaining to porcine circovirus (PCV) transcription and DNA replication. The genome of PCV is circular, single stranded DNA and contains 1759-1768 nucleotides. Both the genome-strand (packaged in the virus particle) and the complementary-strand (synthesized in the new host) encode viral proteins. Among a multitude of RNAs synthesized by alternate splicing, only rep and rep' are essential for virus DNA replication via the rolling-circle replication (RCR) mechanism. In contrast to other RCR biological systems which utilize only one multi-functional protein, Rep, to replicate their respective genomes, PCV requires two proteins, Rep and Rep'. During DNA synthesis, the PCV origin of DNA replication (Ori), which contains a pair of inverted repeats (palindrome), exists in a destabilized four-stranded configuration (the melting-pot model) and permits both the palindromic-strand and the complementary-strand to serve as templates simultaneously for initiation and termination. Inherent in the "melting-pot" model is the template-strand-switching mechanism. This mechanism is the basis for the "correction or conversion" of any mutated nucleotide sequences engineered into either arm of the palindrome and the incorporation of "illegitimate recombination" (addition or deletion of nucleotides) events that are commonly observed at the Ori of other RCR biological systems during DNA replication. PMID- 22036835 TI - Dendritic antioxidants with pyrazole as the core: ability to scavenge radicals and to protect DNA. AB - Chalcones with or without a para-hydroxyl group were condensed with phenylhydrazine-related compounds to form 1,3,5-triphenyl-1H-pyrazole (TPP), 4 (1,5-diphenyl-1H-pyrazol-3-yl)phenol (APP), 4-(1,3-diphenyl-1H-pyrazol-5 yl)phenol (BPP), and 4-(3,5-diphenyl-1H-pyrazol-1-yl)phenol (CPP), in which the phenyl group formed a dendritic structure with pyrazole as the core. Thus, the aim of this work was to explore the antioxidant capacities of TPP, APP, BPP, and CPP in trapping 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(+*)) and 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) and in inhibiting Cu(2+)/glutathione (GSH)-, (*)OH-, and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)-induced oxidation of DNA. TPP can react with ABTS(+*) and DPPH, indicating that the N atom in pyrazole possesses radical-scavenging ability. Moreover, APP, BPP, and CPP can trap 1.71, 1.81, and 1.58 radicals, respectively, in protecting DNA against AAPH-induced oxidation. Thus, the combination of pyrazole with a phenyl group exerted antioxidant ability although only one phenolic hydroxyl group was involved. However, these compounds showed weak protective effect against Cu(2+)/GSH-induced oxidation of DNA and even a pro oxidant effect on (*)OH-induced oxidation of DNA. PMID- 22036836 TI - Retailer branding of consumer sales promotions. A major development in food marketing? AB - This article examines retailer branding of consumer price promotions. It discusses the mechanics of price promotions, consumers' reactions to them and the benefits that accrue to those that use them. It describes how large food retailers can now deploy branded price promotion systems that are fundamentally different to 'traditional' price promotions in both their mechanics and their effects on consumer decision processes. The article describes a field experiment that compared the performance of a food retailer's branded price promotion system with that of a generic (manufacturer) price promotion. The research involved three experiments that covered two food categories (sliced bread and margarine) and two levels of discount (10% and 20%). The results indicate that food retailers are able to attach powerful brands to their price promotion systems, and these brand heuristics can significantly increase consumer purchase intent relative to an equivalent generic/manufacturer promotion. This incremental heuristic effect was stable in both categories and for both levels of price discount studied. These results are consistent with the predictions of alternative, non-cognitive and heuristic based models of food consumer choice that have been published recently in 'Appetite'. PMID- 22036837 TI - Does a population-based multi-factorial lifestyle intervention increase social inequality in dietary habits? The Inter99 study. AB - OBJECTIVE: To investigate whether the effect of an individualised multi-factorial lifestyle intervention on dietary habits differs across socioeconomic groups. METHODS: The study was an individualised multi-factorial lifestyle intervention study with a control group, Inter99 (1999-2006), Copenhagen, Denmark. Participants in the intervention group (n=6 091) received lifestyle intervention during a five-year period. The control group (n=3 324) was followed by questionnaires. Multilevel regression analyses were used, including interaction term between intervention effect and socioeconomic position (SEP) and analysed separately for men and women. SEP was measured as length of education and employment status and dietary habits were measured by a validated food frequency questionnaire. RESULTS: Men with a short education improved their dietary habits more (net-change [95% confidence interval]) (0.25 points [-0.01;0.52]) than men with longer education (0.02 points [-0.09;0.14]), (interaction: p=0.02). Furthermore, unemployed women improved their dietary intake more (0.33 points [0.05;0.61]) than employed women (0.01 points [-0.10;0.11]), (interaction: p=0.03). Similar results were found for fruit intake, whereas no significant interactions were found for fish, fat and vegetable intake. CONCLUSIONS: Individualised dietary interventions do not increase and may even decrease or hinder further widening of the social inequalities in health due to unhealthy dietary habits among socially disadvantaged individuals. PMID- 22036838 TI - The allometry of CNS size and consequences of miniaturization in orb-weaving and cleptoparasitic spiders. AB - Allometric studies of the gross neuroanatomy of adults from nine species of spiders from six web-weaving families (Orbicularia), and nymphs from six of these species, show that very small spiders resemble other small animals in having disproportionately larger central nervous systems (CNSs) relative to body mass when compared with large-bodied forms. Small spiderlings and minute adult spiders have similar relative CNS volumes. The relatively large CNS of a very small spider occupies up to 78% of the cephalothorax volume. The CNSs of very small spiders extend into their coxae, occupying as much as 26% of the profile area of the coxae of an Anapisona simoni spiderling (body mass < 0.005 mg). Such modifications occur both in species with minute adults, and in tiny spiderlings of species with large-bodied adults. In at least one such species, Leucauge mariana, the CNS of the spiderling extends into a prominent ventral bulge of the sternum. Tiny spiders also have reduced neuronal cell body diameters. The adults of nearly all orbicularian spiders weave prey capture webs, as do the spiderlings, beginning with second instar nymphs. Comparable allometric relations occur in adults of both orb-weaving and cleptoparasitic species, indicating that this behavioral difference is not reflected in differences in gross CNS allometry. PMID- 22036839 TI - Modified Lund concept versus cerebral perfusion pressure-targeted therapy: a randomised controlled study in patients with secondary brain ischaemia. AB - PURPOSE: Secondary brain ischaemia (SBI) usually develops after aneurysmal subarachnoid haemorrhage (SAH) and severe traumatic brain injury (TBI). Current approaches to managing these conditions are based either on intracranial pressure targeted therapy (ICP-targeted) with cerebral microdialysis (CM) monitoring according to the modified Lund concept or cerebral perfusion pressure-targeted therapy (CPP-targeted). We present a prospective, randomised controlled study comparing relative effectiveness of the two management strategies. METHODS: Sixty comatose operated patients with SBI following aneurysmal SAH and severe TBI were randomised into ICP-targeted therapy with CM monitoring and CPP-targeted therapy groups. Mortality rates in both groups were calculated and tissue biochemical signs of cerebral ischaemia were analysed using CM. Measured CM data were related to outcome (Glasgow Outcome Scale [GOS] score 1, 2 and 3 for poor outcome or GOS score 4 and 5 for good outcome). RESULTS: Patients treated with ICP-targeted therapy with CM monitoring had significantly lower mortality rate as compared with those treated with CPP-targeted therapy (P=0.03). Patients monitored with CM who had poor outcome had lower mean values of glucose and higher mean values of glycerol and lactate/pyruvate ratio as compared with those who had good outcome (glucose: P=0.003; glycerol: P=0.02; lactate/pyruvate ratio: P=0.01). There was no difference in the mortality outcome between aneurysmal SAH and severe TBI in the two groups (P=0.28 for ICP-targeted therapy with CM monitoring, P=0.36 for CPP-targeted therapy). Also, there were no differences in the CM values between patients with aneurysmal SAH and severe TBI who underwent ICP-targeted therapy (glucose: P=0.23; glycerol: P=0.41; lactate/pyruvate ratio: P=0.40). CONCLUSION: The modified Lund concept, directed at bedside real-time monitoring of brain biochemistry by CM showed better results compared to CPP-targeted therapy in the treatment of comatose patients sustaining SBI after aneurysmal SAH and severe TBI. PMID- 22036840 TI - Steroidogenic gene expression following D-aspartate treatment in frog testis. AB - Previous studies have provided evidence that D-Asp plays a role in steroid mediated reproductive biology in amphibians, reptiles, birds and mammals. To examine the molecular involvement of D-Asp on steroidogenic pathway regulation, we analysed the expression of StAR, P450 aromatase and 5alphaRed2 mRNAs in Pelophylax esculentus testis, either in relation to the reproductive cycle or D Asp treatment. Basal StAR mRNA levels, as well as D-Asp and testosterone concentrations, were higher in reproductive than in post-reproductive frogs. D Asp treatment increased StAR mRNA expression and immunolocalisation in both the reproductive and post-reproductive periods. In control testis, aromatase mRNA levels were higher in the post-reproductive period, but following D-Asp administration, they increased only in the reproductive period. The level of 5alphaRed2 mRNA was higher in reproductive frogs than in post-reproductive frogs, and it increased after D-Asp treatment only in the post-reproductive phase. Our results suggest that, in P. esculentus testis, D-Asp increases StAR mRNA in both periods, and P450 aromatase and 5alphaRed2 mRNAs at different points during the reproductive cycle. PMID- 22036841 TI - Is secretoneurin a new hormone? AB - Numerous small potentially bioactive peptides are derived from the selective processing of the ~600 amino acid secretogranin II (SgII) precursor, but only the 31-42 amino acid segment termed secretoneurin (SN) is well-conserved from sharks to mammals. Both SNa and SNb paralogs have been identified in some teleosts, likely arising as a result of the specific genome duplication event in this lineage. Only one copy of the putative lamprey SgII (188 amino acids) could be identified which gives rise to a divergent agnathan SN that contains the signature YTPQ-X-LA-X(7)-EL sequence typical of the central core of all known SN peptides. In rodent models, SN has regulatory effects on neuroinflammation and neurotransmitter release, and possesses therapeutic potential for the induction of angiogenesis. The wide distribution of SN in neuroendocrine neurons and pituitary cells suggests important endocrine roles. The clearest example of the endocrine action of SN is the stimulatory effects on pituitary luteinizing hormone release from goldfish pituitary and mouse LbetaT2 gonadotroph cells, indicative of an important role in reproduction. Several lines of evidence suggest that the SN receptor is most likely a G-protein coupled protein. Microarray analysis of SN effects on dispersed goldfish pituitary cells in vitro reveals novel SN actions that include effects on genes involved in notch signaling and the guanylate cyclase pathway. Intracerebroventricular injection of SN increases feeding and locomotory behaviors in goldfish. Given that SgII appeared early in vertebrate evolution, SN is an old peptide with emerging implications as a new multifunctional hormone. PMID- 22036842 TI - Osmoreception: perspectives on signal transduction and environmental modulation. AB - Osmoregulation is essential to life in vertebrates and osmoreception is a fundamental element in osmoregulation. Progress in characterizing the mechanisms that mediate osmoreception has been made possible by using a uniquely accessible cell model, the prolactin (PRL) cell of the euryhaline tilapia, Oreochromis mossambicus. In addition to a brief historical overview, we offer a summary of our recent progress on signal transduction and osmosensitivity in the tilapia PRL cell model. Prolactin is a central regulator of hydromineral balance in teleosts in freshwater (FW). Consistent with its essential role in FW osmoregulation, PRL release in tilapia is inversely related to extracellular osmolality, both in vivo and in vitro. Osmotically-driven changes in PRL cell volume control PRL release. A decrease in extracellular osmolality increases cell volume, leading to a rapid influx of Ca(2+) through stretch-activated channels followed by a sharp rise in PRL release. Our recent studies also suggest that cAMP is involved in the osmotic signal transduction, and that acclimation salinity can modulate PRL cell osmosensitivity. Prolactin cells from FW tilapia show a larger rise in PRL release after a reduction in medium osmolality than those from SW fish. Paradoxically, hyposmotically-induced increase in PRL mRNA was observed only in cells from SW fish. Our studies have revealed differences in the abundance of the water channel, aquaporin 3 (AQP3), and the stretch activated Ca(2+) channel, transient receptor potential vanilloid 4 (TRPV4) in PRL cells of FW and SW fish that may explain their differing osmosensitivity and osmoreceptive output in differing acclimation salinities. PMID- 22036843 TI - A catalytic defect in mitochondrial respiratory chain complex I due to a mutation in NDUFS2 in a patient with Leigh syndrome. AB - In this study, we investigated the pathogenicity of a homozygous Asp446Asn mutation in the NDUFS2 gene of a patient with a mitochondrial respiratory chain complex I deficiency. The clinical, biochemical, and genetic features of the NDUFS2 patient were compared with those of 4 patients with previously identified NDUFS2 mutations. All 5 patients presented with Leigh syndrome. In addition, 3 out of 5 showed hypertrophic cardiomyopathy. Complex I amounts in the patient carrying the Asp446Asn mutation were normal, while the complex I activity was strongly reduced, showing that the NDUFS2 mutation affects complex I enzymatic function. By contrast, the 4 other NDUFS2 patients showed both a reduced amount and activity of complex I. The enzymatic defect in fibroblasts of the patient carrying the Asp446Asn mutation was rescued by transduction of wild type NDUFS2. A 3-D model of the catalytic core of complex I showed that the mutated amino acid residue resides near the coenzyme Q binding pocket. However, the K(M) of complex I for coenzyme Q analogs of the Asp446Asn mutated complex I was similar to the K(M) observed in other complex I defects and in controls. We propose that the mutation interferes with the reduction of coenzyme Q or with the coupling of coenzyme Q reduction with the conformational changes involved in proton pumping of complex I. PMID- 22036844 TI - Hypoxia-inducible factor-1 alpha regulates prion protein expression to protect against neuron cell damage. AB - The human prion protein fragment, PrP (106-126), may contain a majority of the pathological features associated with the infectious scrapie isoform of PrP, known as PrP(Sc). Based on our previous findings that hypoxia protects neuronal cells from PrP (106-126)-induced apoptosis and increases cellular prion protein (PrP(C)) expression, we hypothesized that hypoxia-related genes, including hypoxia-inducible factor-1 alpha (HIF-1alpha), may regulate PrP(C) expression and that these genes may be involved in prion-related neurodegenerative diseases. Hypoxic conditions are known to elicit cellular responses designed to improve cell survival through adaptive processes. Under normoxic conditions, a deferoxamine-mediated elevation of HIF-1alpha produced the same effect as hypoxia inhibited neuron cell death. However, under hypoxic conditions, doxorubicin suppressed HIF-1alpha attenuated the inhibitory effect on neuron cell death mediated by PrP (106-126). Knock-down of HIF-1alpha using lentiviral short hairpin (sh) RNA-induced downregulation of PrP(C) mRNA and protein expression under hypoxic conditions, and sensitized neuron cells to prion peptide-mediated cell death even in hypoxic conditions. In PrP(C) knockout hippocampal neuron cells, hypoxia increased the HIF-1alpha protein but the cells did not display the inhibitory effect of prion peptide-induced neuron cell death. Adenoviruses expressing the full length Prnp gene (Ad-Prnp) were utilized for overexpression of the Prnp gene in PrP(C) knockout hippocampal neuron cells. Adenoviral transfection of PrP(C) knockout cells with Prnp resulted in the inhibition of prion peptide-mediated cell death in these cells. This is the first report demonstrating that expression of normal PrP(C) is regulated by HIF-1alpha, and PrP(C) overexpression induced by hypoxia plays a pivotal role in hypoxic inhibition of prion peptide-induced neuron cell death. These results suggest that hypoxia-related genes, including HIF-1alpha, may be involved in the pathogenesis of prion-related diseases and as such may be a therapeutic target for prion related neurodegenerative diseases. PMID- 22036845 TI - Anti-asthmatic effect of ASP3258, a novel phosphodiesterase 4 inhibitor. AB - ASP3258 is a potent and selective PDE4 inhibitor and exerts a wide-range of anti inflammatory effects with low emetic potential, a major adverse effect of PDE4 inhibitors. Here, we investigated the anti-asthmatic potency of ASP3258 as compared with those of two representative PDE4 inhibitors: roflumilast and cilomilast. Orally administered ASP3258, roflumilast, and cilomilast all inhibited ovalbumin (OVA)-induced eosinophil infiltration into the airway of sensitized Brown Norway rats with ED(50) values of 0.81, 0.46, and 4.4 mg/kg, respectively. Histological examination also revealed a decreasing trend in inflammatory cell infiltration into the lung following ASP3258 administration. In vitro investigation of bronchodilatory activities showed that these compounds (10(-8)-10(-6) M) concentration-dependently inhibited OVA-induced contraction of trachea isolated from sensitized guinea pigs but had no effect on spasmogen precontracted tracheal tension prepared from non-sensitized guinea pigs up to 10( 6) M. In vivo experiments using sensitized guinea pigs showed that these orally administered compounds inhibited OVA-induced increases in airway resistance with ED(50) values of 2.2, 0.35, and 12 mg/kg, respectively. Further, orally administered ASP3258 (0.1 and 1 mg/kg), roflumilast (0.1 and 1 mg/kg), and cilomilast (10 mg/kg) significantly suppressed airway hyperresponsiveness caused by OVA exposure. ASP3258's potent inhibition of antigen-induced bronchoconstriction and airway hyperresponsiveness, two characteristic symptoms of bronchial asthma, suggests that this compound will be useful in treating asthma. PMID- 22036846 TI - Image resampling effects in mammographic image simulation. AB - This work describes the theory of resampling effects within the context of image simulation for mammographic images. The process of digitization associated with using digital imaging technology needs to be correctly addressed in any image simulation process. Failure to do so can lead to overblurring in the final synthetic image. A method for weighted neighbourhood averaging is described for non-integer scaling factors in resampling images. The use of the method is demonstrated by comparing simulated and real images of an edge test object acquired on two clinical mammography systems. Images were simulated using two setups: from idealized images and from images obtained with clinical systems. A Gaussian interpolation method is proposed as a single-step solution to modelling blurring filters for the simulation process. PMID- 22036847 TI - National Society Cardiovascular Journals of Europe: Almanac 2011. PMID- 22036848 TI - Pro- or anti-inflammatory properties of the adipokine dipeptidyl peptidase-4? PMID- 22036849 TI - Acute pancreatitis: an uncommon but easily treatable cause. PMID- 22036850 TI - Adult-onset cerebellar ataxia due to mutations in CABC1/ADCK3. AB - OBJECTIVE: Inherited ataxias are heterogeneous disorders affecting both children and adults. The primary cause can be identified in about half of the patients and only very few can receive causative therapy. METHODS: The authors performed sequencing of known Coenzyme Q10 (CoQ10) deficiency genes in 22 patients with unexplained recessive or sporadic ataxia. RESULTS: CABC1/ADCK3 mutations were detected in four patients and two siblings presenting with cerebellar ataxia, epilepsy and muscle symptoms. Spasticity, dystonia, tremor and migraine were variably present; cognitive impairment was severe in early childhood cases, but was absent in adults. In contrast to previous reports, two of the patients had a later-onset, very mild phenotype and remained ambulatory in their late forties. Muscle biopsy revealed lipid accumulation, mitochondrial proliferation and cytochrome c oxidase-deficient fibres, but no typical ragged red fibres. Respiratory-chain enzyme activities and CoQ10 were decreased in severely affected patients but remained normal in a mildly affected patient at 46 years of age. CONCLUSIONS: These observations highlight the importance of screening for a potentially treatable cause, CABC1/ADCK3 mutations, not only in severe childhood onset ataxia, but also in patients with mild cerebellar ataxia in adult life. PMID- 22036853 TI - Osteopontin is involved in urotensin II-induced migration of rat aortic adventitial fibroblasts. AB - Recent studies suggest that both osteopontin and urotensin II (UII) play critical roles in vascular remodeling. We previously showed that UII could stimulate the migration of aortic adventitial fibroblasts. In this study, we examined whether osteopontin is involved in UII-induced migration of rat aortic adventitial fibroblasts and examined the effects and mechanisms of UII on osteopontin expression in adventitial fibroblasts. Migration of adventitial fibroblasts induced by UII could be inhibited significantly by osteopontin antisense oligonucleotide (P<0.01) but not sense or mismatch oligonucleotides (P>0.05). Moreover, UII dose- and time-dependently promoted osteopontin mRNA expression and protein secretion in the cells, with maximal effect at 10(-8)mol/l at 3h for mRNA expression or at 12h for protein secretion (both P<0.01). Furthermore, the UII effects were significantly inhibited by its receptor antagonist SB710411 (10( 6)mol/l), and Ca(2+) channel blocker nicardipine (10(-5)mol/l), protein kinase C (PKC) inhibitor H7 (10(-5)mol/l), calcineurin inhibitor cyclosporine A (10( 5)mol/l), mitogen-activated protein kinase (MAPK) inhibitor PD98059 (10(-5)mol/l) and Rho kinase inhibitor Y-27632 (10(-5)mol/l). Thus, osteopontin is involved in the UII-induced migration of adventitial fibroblasts, and UII could upregulate osteopontin gene expression and protein synthesis in rat aortic adventitial fibroblasts by activating its receptor and the Ca(2+) channel, PKC, calcineurin, MAPK and Rho kinase signal transduction pathways. PMID- 22036854 TI - Long-term outcome of patients hospitalized in intensive care units with central or extrapontine myelinolysis*. AB - OBJECTIVE: Very few data are available for critically ill patients with central or extrapontine myelinolysis and according to available evidence, the prognosis seems to be poor. We aimed to describe the baseline characteristics, the management, the long-term prognosis, and the prognostic factors in central or extrapontine myelinolysis. DESIGN: Retrospective observational study considering modified Rankin Scale score >3 or death as an unfavorable outcome. SETTING: Forty six French intensive care units. PATIENTS: Thirty-six patients with central or extrapontine myelinolysis treated in 2000-2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At baseline, 31 (86%) patients were alcoholics and 33 (92%) presented with hyponatremia. Mechanical ventilation was required in 32 (89%) patients. At 1-yr follow-up, 11 (31%) patients have died, whereas 14 (56%) survivors have returned to a Rankin score <= 1. Life-supporting therapies were withheld in 11 (31%) patients. Severe cerebral motor disability was the most frequently cited reason. However, five of them were still alive at 1 yr with Rankin score <= 1 for four of them. We found no statistical difference between the 18 (50%) patients with a favorable outcome and the 18 (50%) patients with an unfavorable outcome with regard to severity of illness, suggesting that recovery is possible and unpredictable on the basis of clinical presentation. Chronic alcoholism was less frequent in patients with a favorable outcome as compared with patient with an unfavorable outcome (13 [72%] vs. 18 [100%], p = .04). CONCLUSIONS: The prognosis of critically ill patients with central or extrapontine myelinolysis is better than thus far thought despite initial severe clinical manifestations. Regarding the high rate of decisions to withhold life supporting therapies, the probability of a favorable outcome might be underestimated by intensivists. PMID- 22036855 TI - Protective effects of melanocortins on short-term changes in a rat model of traumatic brain injury*. AB - OBJECTIVE: Treatment for traumatic brain injury remains elusive despite compelling evidence from animal models for a variety of therapeutic targets. Melanocortins have established neuroprotective effects against experimental ischemic stroke. We investigated whether melanocortin treatment of traumatic brain injury induces neuroprotection and promotes functional recovery. DESIGN: Randomized experiment. SETTING: Research laboratory at a university hospital. SUBJECTS: Male Sprague-Dawley rats (n = 215). INTERVENTIONS: Experimental rat model of diffuse traumatic brain injury, the impact-acceleration model. MEASUREMENT AND MAIN RESULTS: Brain tissue nitrites, phosphorylation level of extracellular signal-regulated kinases, and c-jun N-terminal kinases; and expression of active caspase-3, tumor necrosis factor-alpha, BAX, and Bcl-2 as well as serum levels of interleukin-6, high mobility group box-1, interleukin-10, and brain histologic damage were evaluated 24 or 48 hrs after the insult. Sensorimotor orientation and limb use were evaluated at day 7 and learning and memory at days 23-30 after injury. Posttraumatic treatment every 12 hrs with the melanocortin analog [Nle, D-Phe]-alpha-melanocyte-stimulating hormone (starting 3 or 6 hrs after injury) inhibited traumatic brain injury-induced upregulation of nitric oxide synthesis, phosphorylation level of extracellular signal-regulated kinases, phosphorylation level of c-jun N-terminal kinases, and active caspase-3; reduced expressions/levels of tumor necrosis factor-alpha, BAX, interleukin-6, and high mobility group box-1; and increased those of Bcl-2 and interleukin-10. These molecular changes were associated with a reduction in brain tissue damage, as highlighted by histopathological findings and improved functional recovery. Pretreatment with the melanocortin MC4 receptor antagonist HS024 abated the positive effects of [Nle, D-Phe]-alpha-melanocyte-stimulating hormone. CONCLUSIONS: Our data indicate that melanocortins protect against traumatic brain injury, in a broad time window and through activation of MC4 receptors, by counteracting the main traumatic brain injury-related mechanisms of damage. These findings could have major clinical implications. PMID- 22036856 TI - Induced hypothermia is protective in a rat model of pneumococcal pneumonia associated with increased adenosine triphosphate availability and turnover*. AB - OBJECTIVE: To determine the effect of induced hypothermia on bacterial growth, lung injury, and mitochondrial function in a rat model of pneumococcal pneumosepsis. DESIGN: Animal study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Subjects were inoculated intratracheally with Streptococcus pneumoniae and controls received saline. After the development of pneumonia, mechanical ventilation was started with or without induced mild hypothermia (32 degrees C). Bacterial growth and inflammatory markers were determined in bronchoalveolar lavage fluid, blood, and organs. Oxidative phosphorylation and adenosine triphosphate contents were measured in mitochondria isolated from the liver and soleus muscle. MEASUREMENTS AND MAIN RESULTS: Inoculation with S. pneumoniae resulted in severe pneumonia with bacterial dissemination, distal organ injury, and blunted peripheral oxygen consumption on mechanical ventilation. Hypothermia did not affect bacterial growth in bronchoalveolar lavage fluid and in homogenized lungs compared with normothermic controls but was associated with reduced bacterial dissemination to the spleen with a trend toward reduced bacterial load in blood and liver. Hypothermia reduced lung injury, exemplified by reductions in pulmonary cell influx and bronchoalveolar lavage fluid protein levels compared with controls. Hypothermia reduced bronchoalveolar lavage fluid levels of interleukin-1beta, tended to reduce bronchoalveolar lavage fluid CINC-3 levels, but no effect was observed on bronchoalveolar lavage fluid tumor necrosis factor-alpha and interleukin-6 levels. Induced hypothermia restored the fall in oxygen consumption and adenosine triphosphate levels in the liver, whereas adenosine triphosphate/adenosine diphosphate ratios remained low. In muscle, induced hypothermia also reversed low oxygen consumption as a result of pneumonia, but with an increase in adenosine triphosphate levels, whereas adenosine triphosphate/adenosine diphosphate ratios were low. CONCLUSION: Hypothermia did not adversely affect bacterial growth, but rather reduced bacterial dissemination in a rat model of pneumococcal pneumosepsis. Furthermore, hypothermia reduced lung injury associated with restored adenosine triphosphate availability and turnover. These findings suggest that hypothermia may reduce organ injury by preventing sepsis-related mitochondrial dysfunction. PMID- 22036857 TI - Extravascular lung water predicts progression to acute lung injury in patients with increased risk*. AB - OBJECTIVES: To compare the extravascular lung water index and other markers of disease severity in patients with acute lung injury vs. patients at risk for development of acute lung injury and to determine their ability to predict progression to acute lung injury in patients at risk. DESIGN: Extravascular lung water index, dead space fraction, PaO2/FIO2, and other markers of disease severity were measured prospectively in 29 patients daily for 5 days after admission to the intensive care unit. Patients had acute lung injury as defined by the American European Consensus Committee criteria or had risk factors for development of it. SETTING: The intensive care units of an academic tertiary referral hospital. MEASUREMENTS AND MAIN RESULTS: The mean extravascular lung water index on day 1 for patients who progressed to acute lung injury was higher than for those who did not (15.5 +/- 7.4 mL/kg vs. 8.7 +/- 2.3 mL/kg; p = .04). None of the other physiologic parameters tested discriminated progression to acute lung injury to include the mean physiologic dead space (0.61 +/- 0.06] vs. 0.59 +/- 0.10; p = .67), PaO2/FIO2 ratio (322 +/- 35 vs. 267 +/- 98; p = .15), and static lung compliance (30.9 +/- 13.5 vs. 38.5 +/- 11.7; p = .24). An extravascular lung water index cutoff value on day 1 of 10 mL/kg had a 63% sensitivity, 88% specificity, positive predictive value of 83%, and negative predictive value of 70% to predict progression to acute lung injury. There was no difference in extravascular lung water index between those who progressed to acute lung injury vs. those who had acute lung injury (14.3 +/- 4.7 vs. 15.5 +/- 7.4; p = .97). CONCLUSIONS: Elevated extravascular lung water index is a feature of early acute lung injury and discriminates between those with acute lung injury and those without. Furthermore, extravascular lung water index predicts progression to acute lung injury in patients with risk factors for development of acute lung injury 2.6 +/- 0.3 days before the patients meet American European Consensus Committee criteria for it. These 2.6 +/- 0.3 days may then represent missed opportunity for therapeutic intervention and improved outcome. PMID- 22036858 TI - Deviations from evidence-based clinical management guidelines increase mortality in critically injured trauma patients*. AB - OBJECTIVES: The effect of treatment guidelines on clinical outcomes in general and specifically for trauma patients has not been well-studied. We hypothesized that better compliance with guidelines would be associated with improved clinical outcomes. DESIGN: Prospective, randomized, double-blinded, multicentered, placebo controlled study of recombinant factor VII in severe trauma that utilized guidelines for damage control, transfusions, and mechanical ventilation. Vanderbilt Coordinating Center reviewed compliance in near real-time and reported deviations classified as minor, moderate, or major to investigators. Multivariate regression analysis measured the association between outcomes (30-day and 90-day mortality, development of multiple organ failure, ventilator-free days, renal failure-free days, and blood products transfused) and compliance with each guideline, as well as a composite assessment of overall compliance. SETTING: One hundred hospitals in 26 countries. PATIENTS: Blunt and/or penetrating trauma patients aged 18-70 yrs who had received 4-8 units of red blood cells for active torso and/or proximal lower extremity bleeding despite standard interventions. MEASUREMENTS AND MAIN RESULTS: When assessed as composite end point, major deviations from guidelines were associated with significantly higher mortality at 30 and 90 days after injury and fewer renal failure-free days. Moderate deviations were associated with a significantly higher risk of multiple organ failure and fewer ventilator-free days. Moderate and major deviations from damage control and ventilation guidelines were also significantly associated with higher risk of death at days 30 and 90. Within the ventilation protocol, noncompliance with tidal volume and plateau pressure targets was associated with significantly higher mortality at days 30 and 90 and fewer ventilator-free days, whereas noncompliance with weaning guideline was only associated with significantly fewer ventilator-free days. CONCLUSIONS: : In a clinical trial of trauma patients, higher compliance with guidelines for damage control, transfusion, and ventilation management is associated with lower mortality and improved outcomes. PMID- 22036859 TI - Analysis of risk factors for adverse drug events in critically ill patients*. AB - OBJECTIVES: An evaluation of risk factors for adverse drug events in critically ill patients has not been previously studied. The purpose of this original study was to determine risk factors for adverse drug events in critically ill adult patients. DESIGN: This retrospective case-control study includes patients who were admitted to the intensive care unit during a 7.5-yr period. SETTING: Academic medical center with 647 beds that contains approximately 120 intensive care unit beds. PATIENTS: Patients in the case group experienced an adverse drug event as documented in the hospital's database. The control group comprised the next two patients admitted to the same intensive care unit by the same admitting service. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-nine suspected risk factors identified from the literature were evaluated, including patient characteristics, drug characteristics, and laboratory values using a multiple logistic regression. A sample of 1101 cases and controls (54% male), with a mean age of 59.4 +/- 17.5 yrs, were identified. In 367 cases, there was a total of 499 documented adverse drug events. Patients with kidney injury, thrombocytopenia, and those admitted emergently were 16-times, 3-times, and 2 times more likely to have an adverse drug event, respectively. Patients who were administered intravenous medications had a 3% higher risk of having an adverse drug event for each drug dispensed. Overall, the case group received more drugs per intensive care unit day and more drugs per intensive care unit stay. CONCLUSIONS: Several patient and drug-related characteristics contribute to the risk of adverse drug events in critically ill patients. Diligent monitoring of factors that can influence the pharmacokinetic properties for existing drug therapies is necessary. Drug regimens should be evaluated daily for minimization. Based on previous studies, pharmacists as part of the interdisciplinary team could help to manage these risks. PMID- 22036860 TI - Dopamine versus norepinephrine in the treatment of septic shock: a meta analysis*. AB - OBJECTIVES: There has long-been controversy about the possible superiority of norepinephrine compared to dopamine in the treatment of shock. The objective was to evaluate the effects of norepinephrine and dopamine on outcome and adverse events in patients with septic shock. DATA SOURCES: A systematic search of the MEDLINE, Embase, Scopus, and CENTRAL databases, and of Google Scholar, up to June 30, 2011. STUDY SELECTION AND DATA EXTRACTION: All studies providing information on the outcome of patients with septic shock treated with dopamine compared to norepinephrine were included. Observational and randomized trials were analyzed separately. Because time of outcome assessment varied among trials, we evaluated 28-day mortality or closest estimate. Heterogeneity among trials was assessed using the Cochrane Q homogeneity test. A Forest plot was constructed and the aggregate relative risk of death was computed. Potential publication bias was evaluated using funnel plots. METHODS AND MAIN RESULTS: We retrieved five observational (1,360 patients) and six randomized (1,408 patients) trials, totaling 2,768 patients (1,474 who received norepinephrine and 1,294 who received dopamine). In observational studies, among which there was significant heterogeneity (p < .001), there was no difference in mortality (relative risk, 1.09; confidence interval, 0.84-1.41; p = .72). A sensitivity analysis identified one trial as being responsible for the heterogeneity; after exclusion of that trial, no heterogeneity was observed and dopamine administration was associated with an increased risk of death (relative risk, 1.23; confidence interval, 1.05 1.43; p < .01). In randomized trials, for which no heterogeneity or publication bias was detected (p = .77), dopamine was associated with an increased risk of death (relative risk, 1.12; confidence interval, 1.01-1.20; p = .035). In the two trials that reported arrhythmias, these were more frequent with dopamine than with norepinephrine (relative risk, 2.34; confidence interval, 1.46-3.77; p = .001). CONCLUSIONS: In patients with septic shock, dopamine administration is associated with greater mortality and a higher incidence of arrhythmic events compared to norepinephrine administration. PMID- 22036861 TI - High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats. AB - AIM: To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats. METHODS: Female Sprague Dawley rats were randomly separated into 3 groups: (1) the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food, 3% cholesterol and 20% lard for 3 months; (2) ovariectomised (OVX) rats were bilaterally ovariectomised and fed a standard diet; and (3) the control rats were fed the standard diet. Bone mineral density (BMD) of the rats was measured using dual-energy X-ray absorptiometry. Serum levels of oestradiol (E2), osteocalcin (BGP) and carboxy-terminal collagen crosslinks (CTX) were measured using ELISA. Gene expression profile was determined with microarray. Mouse osteoblast cells (MC3T3-E1) were used for in vitro study. Proliferation, differentiation and oxidative stress of the osteoblasts were investigated using MTT, qRT-PCR and biochemical methods. RESULTS: In high cholesterol fed rats, the femur BMD and serum BGP level were significantly reduced, while the CTX level was significantly increased. DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats. Of these genes, 1626 were also down-regulated and 1466 were up-regulated in OVX rats. In total, 370 genes were up-regulated in both groups, and 976 genes were down-regulated. Some of the down regulated genes were found to code for proteins involved in the transforming growth factor beta (TGF-beta)/bone morphogenic protein (BMP) and Wnt signaling pathways. The up-regulated genes were found to code for IL-6 and Ager with bone resorption functions. Treatment of MC3T3-E1 cells with cholesterol (12.5-50 MUg/mL) inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner. The treatment also concentration-dependently reduced the expression of BMP2 and Cbfa1, and increased the oxidative injury in MC3T3-E1 cells. CONCLUSION: The results suggest a close correlation between hypercholesterolaemia and osteoporosis. High cholesterol diet increases the risk of osteoporosis, possible via inhibiting the differentiation and proliferation of osteoblasts. PMID- 22036862 TI - Tolerance and pharmacokinetics of single-dose intravenous hemoporfin in healthy volunteers. AB - AIM: To investigate the safety, tolerability and pharmacokinetics of intravenous hemoporfin, a novel photosensitive drug for the treatment of port-wine stain (PWS), in healthy Chinese volunteers following single-dose administration. METHODS: Thirty-six healthy Chinese subjects were enrolled. The subjects were administered hemoporfin (2.5, 5, 7.5 or 10 mg/kg) via single-dose intravenous infusion. Pharmacokinetics of the drug were studied in the groups with doses of 2.5, 5 and 7.5 mg/kg, and tolerability was studied in all the 4 groups. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters, and pharmacokinetics were assessed by determining hemoporfin content with a validated high-performance liquid chromatography with fluorescence detection (HPLC/FLD) method. RESULTS: Mild and transient adverse events occurred in the trial (n=10), but none were serious, and no subjects were withdrawn from the trial. The gastrointestinal tract adverse events, such as nausea, stomach upset, abdominal pain and vomiting, were observed in the groups with doses of 7.5 and 10 mg/kg. Increased alanine aminotransferase (ALT) concentration was found in 3 subjects, and increased alkaline phosphatase (ALP) concentration in one subject. The half-life of hemoporfin for doses of 2.5, 5, and 7.5 mg/kg was 1.26 h, 1.31 h, and 1.70 h, respectively. C(max) and AUC increased with dose for intravenous single-dose administration of hemoporfin in the 2.5, 5, and 7.5 mg/kg groups. Urinary excretion of hemoporfin within 12 h was less than 0.2%. CONCLUSION: Hemoporfin is safe and well-tolerated in healthy Chinese volunteers at a single intravenous dose of up to 10 mg/kg. It was rapidly cleared from the blood and had a short half-life, which insures a short light-avoidance period. PMID- 22036863 TI - Integrin activation as an alternative treatment approach for inflammatory diseases. PMID- 22036864 TI - Cell adhesion, inflammation and therapy: old ideas and a significant step forward. PMID- 22036865 TI - Oxidized low-density lipoprotein and beta-glycerophosphate synergistically induce endothelial progenitor cell ossification. AB - AIM: To investigate the ability of ox-LDL to induce ossification of endothelial progenitor cells (EPCs) in vitro and explored whether oxidative stress, especially hypoxia inducible factor-1alpha (HIF-1alpha) and reactive oxygen species (ROS), participate in the ossific process. METHODS: Rat bone marrow derived endothelial progenitor cells (BMEPCs) were cultured in endothelial growth medium supplemented with VEGF (40 ng/mL) and bFGF (10 ng/mL). The cells were treated with oxidized low-density lipoprotein (ox-LDL, 5 MUg/mL) and/or beta glycerophosphate (beta-GP, 10 mmol/L). Calcium content and Von Kossa staining were used as the measures of calcium deposition. Ossific gene expression was determined using RT-PCR. The expression of osteocalcin (OCN) was detected with immunofluorescence. Alkaline phosphatase (ALP) activity was analyzed using colorimetric assay. Intercellular reactive oxygen species (ROS) were measured with flow cytometry. RESULTS: BMEPCs exhibited a spindle-like shape. The percentage of cells that expressed the cell markers of EPCs CD34, CD133 and kinase insert domain-containing receptor (KDR) were 46.2%+/-5.8%, 23.5%+/-4.0% and 74.3%+/-8.8%, respectively. Among the total cells, 78.3%+/-4.2% were stained with endothelial-specific fluorescence. Treatment of BMEPCs with ox-LDL significantly promoted calcium deposition, which was further significantly enhanced by co-treatment with beta-GP. The same treatments significantly increased the gene expression of core-binding factor a-1 (cbfa-1) and OCN, while decreased the gene expression of osteoprotegerin (OPG). The treatments also significantly enhanced the activity of ALP, but did not affect the number of OCN(+) cells. Furthermore, the treatments significantly increased ROS and activated the hypoxia inducible factor-1alpha (HIF-1alpha). In all these effects, ox-LDL acted synergistically with beta-GP. CONCLUSION: Ox-LDL and beta-GP synergistically induce ossification of BMEPCs, in which an oxidizing mechanism is involved. PMID- 22036866 TI - Why do anti-inflammatory therapies fail to improve insulin sensitivity? AB - Chronic inflammation occurs in obese conditions in both humans and animals. It also contributes to the pathogenesis of type 2 diabetes (T2D) through insulin resistance, a status in which the body loses its ability to respond to insulin. Inflammation impairs insulin signaling through the functional inhibition of IRS-1 and PPARgamma. Insulin sensitizers (such as rosiglitazone and pioglitazone) inhibit inflammation while improving insulin sensitivity. Therefore, anti inflammatory agents have been suggested as a treatment strategy for insulin resistance. This strategy has been tested in laboratory studies and clinical trials for more than 10 years; however, no significant progress has been made in any of the model systems. This status has led us to re-evaluate the biological significance of chronic inflammation in obesity. Recent studies have consistently asserted that obesity-associated inflammation helps to maintain insulin sensitivity. Inflammation stimulates local adipose tissue remodeling and promotes systemic energy expenditure. We propose that these beneficial activities of inflammation provide an underlying mechanism for the failure of anti-inflammatory therapy in the treatment of insulin resistance. Current literature will be reviewed in this article to present evidence that supports this viewpoint. PMID- 22036867 TI - Host immune-related gene responses against highly pathogenic avian influenza virus infection in vitro differ among chicken cell lines established from different organs. AB - Highly pathogenic avian influenza virus (HPAIV) induces acute disease in chickens causing high mortality and morbidity and is a major threat to poultry industries in Southeast Asian countries. The mechanisms of disease manifestation and host innate immune responses against HAPIV in chickens are not well understood. In this study, we examined virus replication and host gene expressions in four chicken cell lines in vitro to elucidate the impact of host innate immune responses against viral replication. It was demonstrated that viral replication efficiencies were different depending on the cell line. The viral replication appeared to be affected by the basal expression of IFN related genes. The expression of immune-related genes against the viral infection also varied in a cell line dependent manner. In non-immune derived cell lines, but not in immune derived cell lines, the expression of the CCL5 and CCL20 genes were induced by HPAIV infection. Reverse genetics HPAIV, with internal genes from avirulent avian influenza, reduced virus replication and affected immune-related gene expression in a cell line dependent manner. These results suggest the possibility that differential immune responses in different cell types in local tissues could modulate the consequences of HPAIV infection in chickens. PMID- 22036868 TI - Laminitis after 2000 years: adding bricks to our wall of knowledge. PMID- 22036869 TI - Serotypes and virulence genes of extraintestinal pathogenic Escherichia coli isolates from diseased pigs in China. AB - Extraintestinal pathogenic Escherichia coli (ExPEC) isolates were detected in 315/3127 (10.1%) diseased pigs from 19 provinces of China; the frequency of isolation increased from 3.1% in 2004 to 14.6% in 2007. All isolates were characterised for O serogroups, haemolysis, phenotypic and genotypic antimicrobial resistance, virulence genes and pathogenicity. The most prevalent serogroups were O161, O8, O11, O138, O101 and O26; 83/315 (26.3%) isolates were haemolytic. Forty percent of isolates in phylogenetic groups B2 and D were highly virulent porcine ExPEC strains. Thirty-three putative extraintestinal virulence factor genes that are normally associated with human and/or avian ExPEC strains were widely present in porcine isolates. These results indicate that ExPEC are prevalent in pigs in China and represent a potential public health threat. PMID- 22036870 TI - Rhodococcus equi pneumonia in the foal--part 2: diagnostics, treatment and disease management. AB - Various challenges face clinicians and farm managers in diagnosing, treating and preventing Rhodococcus equi pneumonia. The use of ultrasound imaging has aided in the early diagnosis of the disease, reducing treatment duration and improving therapeutic outcomes. Antimicrobial resistance in R. equi is an emerging issue that necessitates prudent antimicrobial therapy of diseased foals. Alternative methods of disease transmission, such as contagious foal-to-foal aerosol transmission, may need to be addressed to complement dust reduction environmental strategies and to minimise the overall risk of exposure of foals to highly concentrated inhaled doses of the organism. Effective management of foals and land aimed at reducing aerosol exposure to virulent R. equi is likely to yield significant reductions in the prevalence and severity of R. equi pneumonia. PMID- 22036871 TI - Exercise training improves exercise capacity in adult patients with a systemic right ventricle: a randomized clinical trial. AB - OBJECTIVE: To assess whether exercise training in adult patients with a systemic right ventricle (RV) improves exercise capacity and quality of life and lowers serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels. DESIGN: Multi-centre parallel randomized controlled trial. PARTICIPANTS: Patients with a systemic RV due to congenitally or surgically corrected transposition of the great arteries. METHODS: Fifty-four adult patients with a systemic RV, were randomized using unmarked opaque envelopes to an intervention group (n = 28) with three training sessions per week for 10 consecutive weeks, and a control group (n = 26). Randomization was stratified by participating centre. At baseline, and follow-up, we determined maximal exercise capacity (V'O(2peak)), serum NT-proBNP levels, and quality of life by means of the SF-36, and the TAAQOL Congenital Heart Disease questionnaires. The final analysis was performed by linear regression, taking into account the stratified randomization. RESULTS: Forty-six patients were analysed (male 50%, age 32 +/- 11 years, intervention group n = 24, control group n = 22). Analysis at 10 weeks showed a significant difference in V'O(2peak) (3.4 mL/kg/min, 95% CI: 0.2 to 6.7; P = 0.04) and resting systolic blood pressure (-7.6 mmHg, 95% CI: -14.0 to -1.3; P = 0.03) in favour of the exercise group. No significant changes were found in serum NT-proBNP levels or quality of life in the intervention group or in the control group nor between groups. None of the patients in the intervention group had to discontinue the training programme due to adverse events. CONCLUSION: In adult patients with a systemic RV exercise training improve exercise capacity. We recommend to revise restrictive guidelines, and to encourage patients to become physically active. ( TRIAL REGISTRATION: The study was registered at http://trialregister.nl. Identifier: NTR1909.). PMID- 22036872 TI - Predictors of in-hospital mortality in elderly patients with acute venous thrombo embolism: the SWIss Venous ThromboEmbolism Registry (SWIVTER). AB - AIMS: Although acute venous thrombo-embolism (VTE) often afflicts patients with advanced age, the predictors of in-hospital mortality for elderly VTE patients are unknown. METHODS AND RESULTS: Among 1247 consecutive patients with acute VTE from the prospective SWIss Venous ThromboEmbolism Registry (SWIVTER), 644 (52%) were elderly (>=65 years of age). In comparison to younger patients, the elderly more often had pulmonary embolism (PE) (60 vs. 42%; P< 0.001), cancer (30 vs. 20%; P< 0.001), chronic lung disease (14 vs. 8%; P= 0.001), and congestive heart failure (12 vs. 2%; P< 0.001). Elderly VTE patients were more often hospitalized (75 vs. 52%; P< 0.001), and there was no difference in the use of thrombolysis, catheter intervention, or surgical embolectomy between the elderly and younger PE patients (5 vs. 6%; P= 0.54), despite a trend towards a higher rate of massive PE in the elderly (8 vs. 4%; P= 0.07). The overall in-hospital mortality rate was 6.6% in the elderly vs. 3.2% in the younger VTE patients (P= 0.033). Cancer was associated with in-hospital death both in the elderly [hazard ratio (HR) 4.91, 95% confidence interval (CI) 2.32-10.38; P< 0.001] and in the younger patients (HR 4.90, 95% CI 1.37-17.59; P= 0.015); massive PE was a predictor of in-hospital death in the elderly only (HR 3.77, 95% CI 1.63-8.74; P= 0.002). CONCLUSION: Elderly patients had more serious VTE than younger patients, and massive PE was particularly life-threatening in the elderly. PMID- 22036873 TI - Evolution of requests to hasten death among patients managed by palliative care teams in France: a multicentre cross-sectional survey (DemandE). AB - BACKGROUND: Strongly marked ideological positions on the impact of palliative care and limited hard data plague the debate on physician-assisted death. METHODS: A national cross-sectional study on the requests to hasten death (RHD) was conducted among 789 French palliative care organisations. Data were collected for all patients with RHD encountered during year 2010. Data on patients' characteristics, medical, psychological and social context, symptoms, nature of palliative management, patient's evolution and palliative care team's interpretation of the request were obtained. FINDINGS: A majority of centres responded and 342 teams provided descriptions of 783 RHD, 476 by a patient, 258 by relatives or close friends and 49 by the nursing staff. Cancer was the most frequent pathology (72%) and 68% of the patients had entered terminal stage. Patients rarely appeared with uncontrolled pain (3.7%), but had difficulties with feeding (65%), moving (54%), excretion (49%), or were cachectic (39%); 31% were considered to be anxio-depressive; 79% did not give physical reasons for their request; 37% of RHD were maintained and 24% fluctuated despite provision of regular follow-up by a palliative care team to 83% of all cases; 68% of patients died within a month; the interpretation of RHD by the staff was a wish for relief (69%), patient's inextricable situation (44%), actual desire not to continue living (36%) or to be helped to die (30%). INTERPRETATION: The large number of described cases provides, for the first time, comprehensive hard data on the evolution of RHDs in a country that has not legalised euthanasia. Whatever the way RHD are expressed, they are frequently maintained despite adequate palliative care with suitable control of pain and psychological support by specialists. PMID- 22036875 TI - High-frequency stimulation restored motor-evoked potentials to the baseline level in the upper extremities but not in the lower extremities under sevoflurane anesthesia in spine surgery. AB - BACKGROUND: Volatile anesthetics attenuate medium-frequency (250 to 500 Hz) pulse train transcranial electrical stimulation (TES) motor-evoked potentials (MEPs) better than propofol. High-frequency (1000 Hz) TES may restore hand MEP amplitude under volatile anesthesia, but its effect on leg MEPs critical for spine surgery monitoring is unknown. METHODS: The effects of sevoflurane and propofol and modulation of the stimulation frequencies on MEPs elicited by TES in the anterior tibial, abductor hallucis, and abductor pollicic brevis muscles were investigated in 31 patients undergoing spine surgery. MEPs elicited by transcranial magnetic stimulation were also obtained before the surgeries and compared with the TES MEPs. RESULTS: Sevoflurane attenuated the MEP amplitudes significantly. The MEP amplitudes increased with the TES frequency in the case of the arms, but not the legs, under sevoflurane anesthesia. The MEPs recorded under propofol anesthesia did not differ from those elicited by transcranial magnetic stimulation before the surgery (control). CONCLUSIONS: Sevoflurane is inadvisable for MEP monitoring in the legs during spine surgery as modulation of the TES frequency did not eliminate the suppressive effect of sevoflurane on the MEPs in the legs. Clinicians should be forewarned of the greater risk of unmonitorable MEPs, especially in the legs, under sevoflurane anesthesia. PMID- 22036874 TI - Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status. AB - BACKGROUND: There are currently no reliable biomarkers for malignant pheochromocytomas and paragangliomas (PPGLs). This study examined whether measurements of catecholamines and their metabolites might offer utility for this purpose. METHODS: Subjects included 365 patients with PPGLs, including 105 with metastases, and a reference population of 846 without the tumour. Eighteen catecholamine-related analytes were examined in relation to tumour location, size and mutations of succinate dehydrogenase subunit B (SDHB). RESULTS: Receiver operating characteristic curves indicated that plasma methoxytyramine, the O methylated metabolite of dopamine, provided the most accurate biomarker for discriminating patients with and without metastases. Plasma methoxytyramine was 4.7-fold higher in patients with than without metastases, a difference independent of tumour burden and the associated 1.6- to 1.8-fold higher concentrations of norepinephrine and normetanephrine. Increased plasma methoxytyramine was associated with SDHB mutations and extra-adrenal disease, but was also present in patients with metastases without SDHB mutations or those with metastases secondary to adrenal tumours. High risk of malignancy associated with SDHB mutations reflected large size and extra-adrenal locations of tumours, both independent predictors of metastatic disease. A plasma methoxytyramine above 0.2nmol/L or a tumour diameter above 5cm indicated increased likelihood of metastatic spread, particularly when associated with an extra-adrenal location. CONCLUSION: Plasma methoxytyramine is a novel biomarker for metastatic PPGLs that together with SDHB mutation status, tumour size and location provide useful information to assess the likelihood of malignancy and manage affected patients. PMID- 22036876 TI - Bilateral Tapia syndrome secondary to oropharyngeal intubation. PMID- 22036877 TI - Copper binding traps the folded state of the SCO protein from Bacillus subtilis. AB - The SCO protein from the aerobic bacterium Bacillus subtilis (BsSCO) is involved in the assembly of the cytochrome c oxidase complex, and specifically with the Cu(A) center. BsSCO has been proposed to play various roles in Cu(A) assembly including, the direct delivery of copper ions to the Cu(A) site, and/or maintaining the appropriate redox state of the cysteine ligands during formation of Cu(A). BsSCO binds copper in both Cu(II) and Cu(I) redox states, but has a million-fold higher affinity for Cu(II). As a prerequisite to kinetic studies, we measured equilibrium stability of oxidized, reduced and Cu(II)-bound BsSCO by chemical and thermal induced denaturation. Oxidized and reduced apo-BsSCO exhibit two-state behavior in both chemical- and thermal-induced unfolding. However, the Cu(II) complex of BsSCO is stable in up to nine molar urea. Thermal or guanidinium-induced unfolding of BsSCO-Cu(II) ensues only as the Cu(II) species is lost. The effect of copper (II) on the folding of BsSCO is complicated by a rapid redox reaction between copper and reduced, denatured BsSCO. When denatured apo-BsSCO is refolded in the presence of copper (II) some of the population is recovered as the BsSCO-Cu(II) complex and some is oxidized indicating that refolding and oxidation are competing processes. The proposed functional roles for BsSCO in vivo require that its cysteine residues are reduced and the presence of copper during folding may be detrimental to BsSCO attaining its functional state. PMID- 22036878 TI - Stable assemblies of cationic bilayer fragments and CpG oligonucleotide with enhanced immunoadjuvant activity in vivo. AB - The cationic lipid dioctadecyldimethylammonium bromide (DODAB) and the CpG oligonucleotide (CpG) have been separately used as potent immunoadjuvants driving Th1 responses. Here DODAB bilayer fragments (BF) and CpG (5'-TTGACGTTCG-3') assemblies have their physical properties and immunoadjuvant activity determined using ovalbumin (OVA) as a model antigen. At 0.1 mg/mL OVA, the dependence of DODAB BF/OVA size and zeta-potential on time and [DODAB] establishes 0.1 mM DODAB as suitable for obtaining stable and cationic DODAB BF/OVA assemblies. At 0.1 mM DODAB, 0.1 mg/mL OVA and 0.006 mM CpG, the zeta-potential is zero. At [CpG]>0.006 mM, good colloidal stability for the anionic assemblies is due to charge overcompensation. At 0.020 mM CpG, these DODAB BF/OVA/CpG assemblies are highly effective in vivo generating responses similar to those elicited by the stable and cationic DODAB BF/OVA. The anti-OVA DTH reaction and the secretion of IFN gamma and IL-12 are 6, 42 and 9 times larger for the DODAB BF/OVA/CpG-immunized mice than the same responses by OVA-immunized mice, respectively. This work shows for the first time that charge of small assemblies is not important to determine the immune response. PMID- 22036879 TI - Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release. AB - Degradable cationic polymers are desirable for in vivo nucleic acid delivery because they offer significantly decreased toxicity over non-degradable counterparts. Peptide linkers provide chemical stability and high specificity for particular endopeptidases but have not been extensively studied for nucleic acid delivery applications. In this work, enzymatically degradable peptide-HPMA copolymers were synthesized by RAFT polymerization of HPMA with methacrylamido terminated peptide macromonomers, resulting in polymers with low polydispersity and near quantitative incorporation of peptides. Three peptide-HPMA copolymers were evaluated: (i) pHCathK(10), containing peptides composed of the linker phe lys-phe-leu (FKFL), a substrate of the endosomal/lysosomal endopeptidase cathepsin B, connected to oligo-(L)-lysine for nucleic acid binding, (ii) pHCath(D)K(10), containing the FKFL linker with oligo-(D)-lysine, and (iii) pH(D)Cath(D)K(10), containing all (D) amino acids. Cathepsin B degraded copolymers pHCathK(10) and pHCath(D)K(10) within 1 h while no degradation of pH(D)Cath(D)K(10) was observed. Polyplexes formed with pHCathK(10) copolymers show DNA release by 4 h of treatment with cathepsin B; comparatively, polyplexes formed with pHCath(D)K(10) and pH(D)Cath(D)K(10) show no DNA release within 8 h. Transfection efficiency in HeLa and NIH/3T3 cells were comparable between the copolymers but pHCathK(10) was less toxic. This work demonstrates the successful application of peptide linkers for degradable cationic polymers and DNA release. PMID- 22036880 TI - Bioreducible polyethylenimine-delivered siRNA targeting human telomerase reverse transcriptase inhibits HepG2 cell growth in vitro and in vivo. AB - One new siRNA sequence was found efficient for human telomerase reverse transcriptase (hTERT) gene silencing in vitro in five types of human cancer cells. Then, a biodegradable polyethylenimine containing multiple disulfide bonds (SS-PEI) was successfully applied as a potent non-viral carrier for intracellular delivery of the hTERT siRNA in vitro and in vivo. The SS-PEI could strongly bind siRNA to form nano-sized and positively-charged complexes, but which were readily destabilized to sufficiently release siRNA in a reducing environment. Transfection experiments showed that the complexes of SS-PEI/hTERT siRNA were able to transfect HepG2 cells in vitro, inducing reduced levels of hTERT mRNA and hTERT protein, decreased telomerase activity, cell growth inhibition and significant cell apoptosis. Besides, treatment with the complexes of SS-PEI/hTERT siRNA could inhibit HepG2 tumor growth in a xenograft mouse model. Importantly, the SS-PEI revealed relatively low cytotoxicity in vitro and at an appropriate dose had no adverse effect on liver and kidney functions in vivo. The results of this study indicate that SS-PEI/siRNA-induced hTERT gene silencing provides a promising method for human cancer gene therapy. PMID- 22036881 TI - Measurement of protein farnesylation and geranylgeranylation in vitro, in cultured cells and in biopsies, and the effects of prenyl transferase inhibitors. AB - The importance of the post-translational lipid modifications farnesylation and geranylgeranylation in protein localization and function coupled with the critical role of prenylated proteins in malignant transformation has prompted interest in their biology and the development of farnesyl transferase and geranylgeranyl transferase inhibitors (FTIs and GGTIs) as chemical probes and anticancer agents. The ability to measure protein prenylation before and after FTI and GGTI treatment is important to understanding and interpreting the effects of these agents on signal transduction pathways and cellular phenotypes, as well as to the use of prenylation as a biomarker. Here we describe protocols to measure the degree of protein prenylation by farnesyl transferase or geranylgeranyl transferase in vitro, in cultured cells and in tumors from animals and humans. The assays use [(3)H]farnesyl diphosphate and [(3)H]geranylgeranyl diphosphate, electrophoretic mobility shift, membrane association using subcellular fractionation or immunofluorescence of intact cells, [(3)H]mevalonic acid labeling, followed by immunoprecipitation and SDS-PAGE, and in vitro transcription, translation and prenylation in reticulocyte lysates. These protocols require from 1 d (enzyme assays) to up to 3 months (autoradiography of [(3)H]-labeled proteins). PMID- 22036882 TI - Ex vivo time-lapse confocal imaging of the mouse embryo aorta. AB - Time-lapse confocal microscopy of mouse embryo slices was developed to access and image the living aorta. In this paper, we explain how to label all hematopoietic and endothelial cells inside the intact mouse aorta with fluorescent directly labeled antibodies. Then we describe the technique to cut nonfixed labeled embryos into thick slices that are further imaged by time-lapse confocal imaging. This approach allows direct observation of the dynamic cell behavior in the living aorta, which was previously inaccessible because of its location deep inside the opaque mouse embryo. In particular, this approach is sensitive enough to allow the experimenter to witness the transition from endothelial cells into hematopoietic stem/progenitor cells in the aorta, the first site of hematopoietic stem cell generation during development. The protocol can be applied to observe other embryonic sites throughout mouse development. A complete experiment requires ~2 d of practical work. PMID- 22036883 TI - Optical sensors for measuring dynamic changes of cytosolic metabolite levels in yeast. AB - Optical sensors allow dynamic quantification of metabolite levels with subcellular resolution. Here we describe protocols for analyzing cytosolic glucose levels in yeast using genetically encoded Forster resonance energy transfer (FRET) sensors. FRET glucose sensors with different glucose affinities (K(d)) covering the low nano- to mid- millimolar range can be targeted genetically to the cytosol or to subcellular compartments. The sensors detect the glucose-induced conformational change in the bacterial periplasmic glucose/galactose binding protein MglB using FRET between two fluorescent protein variants. Measurements can be performed with a single sensor or multiple sensors in parallel. In one approach, cytosolic glucose accumulation is measured in yeast cultures in a 96-well plate using a fluorimeter. Upon excitation of the cyan fluorescent protein (CFP), emission intensities of CFP and YFP (yellow fluorescent protein) are captured before and after glucose addition. FRET sensors provide temporally resolved quantitative data of glucose for the compartment of interest. In a second approach, reversible changes of cytosolic free glucose are measured in individual yeast cells trapped in a microfluidic platform, allowing perfusion of different solutions while FRET changes are monitored in a microscope setup. By using the microplate fluorimeter protocol, 96 cultures can be measured in less than 1 h; analysis of single cells of a single genotype can be completed in <2 h. FRET-based analysis has been performed with glucose, maltose, ATP and zinc sensors, and it can easily be adapted for high-throughput screening using a wide spectrum of sensors. PMID- 22036884 TI - Optical sensors for monitoring dynamic changes of intracellular metabolite levels in mammalian cells. AB - Knowledge of the in vivo levels, distribution and flux of ions and metabolites is crucial to our understanding of physiology in both healthy and diseased states. The quantitative analysis of the dynamics of ions and metabolites with subcellular resolution in vivo poses a major challenge for the analysis of metabolic processes. Genetically encoded Forster resonance energy transfer (FRET) sensors can be used for real-time in vivo detection of metabolites. FRET sensor proteins, for example, for glucose, can be targeted genetically to any cellular compartment, or even to subdomains (e.g., a membrane surface), by adding signal sequences or fusing the sensors to specific proteins. The sensors can be used for analyses in individual mammalian cells in culture, in tissue slices and in intact organisms. Applications include gene discovery, high-throughput drug screens or systematic analysis of regulatory networks affecting uptake, efflux and metabolism. Quantitative analyses obtained with the help of FRET sensors for glucose or other ions and metabolites provide valuable data for modeling of flux. Here we provide a detailed protocol for monitoring glucose levels in the cytosol of mammalian cell cultures through the use of FRET glucose sensors; moreover, the protocol can be used for other ions and metabolites and for analyses in other organisms, as has been successfully demonstrated in bacteria, yeast and even intact plants. The whole procedure typically takes ~4 d including seeding and transfection of mammalian cells; the FRET-based analysis of transfected cells takes ~5 h. PMID- 22036885 TI - Targeting the visceral purinergic system for pain control. AB - Experimental evidence is presented to support the hypothesis that purinergic mechanosensory transduction can initiate visceral pain in urinary bladder, ureter, gut and uterus. In general, physiological reflexes are mediated via P2X3 and P2X2/3 receptors on low threshold sensory fibres, while these receptors on high threshold sensory fibres mediate pain. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by purinergic agents, including P2X3 and P2X2/3 receptor antagonists that are orally bioavailable and stable in vivo and agents that modulate ATP release and breakdown. PMID- 22036886 TI - Financing and systems barriers to seasonal influenza vaccine delivery in community settings. AB - BACKGROUND: Recommendations for annual seasonal influenza vaccination have expanded to now include >300 million children and adults each year. Community settings have become increasingly important venues for influenza vaccination. We sought to identify barriers to and solutions for expanding influenza vaccination in community settings. METHODS: Semi-structured telephone interviews were conducted from 01/09 to 06/10 with a range of stakeholders involved in influenza vaccination, including health plans, medical services firms, retail based clinics, pharmacies, schools, and state and local public health immunization programs. Participants (n=65) were asked about barriers and feasible solutions to influenza vaccine delivery to children and adults in community settings. Key themes were identified through iterative coding using a grounded theory approach. RESULTS: Stakeholders identified specific financial barriers to influenza vaccine delivery in 3 major areas: purchase and distribution, delivery, and reimbursement. Limited purchasing power, the uncertain nature of public demand, and unpredictable timing of influenza vaccine supply were important barriers to enhance delivery in community settings. Barriers to delivery included complexities in running off-site clinics, especially in school settings, the need to manage publicly vs. privately purchased vaccines separately, and state-to state variability in requirements for credentialing, physician oversight, and reporting. Reimbursement barriers included a protracted credentialing process, the need to determine insurance eligibility at point-of-service, and lack of a billing infrastructure in off-site clinics. Opportunities to mitigate financial barriers to influenza vaccine delivery in community settings focused on coordination across providers and the role of public health as a "trusted broker" to overcome existing challenges. CONCLUSIONS: Financial and systems barriers hamper the optimal use of community settings to effectively deliver influenza vaccines. Public health partners at the federal, state, and local levels are well positioned to facilitate the engagement of all stakeholders in this important and complex vaccine delivery system. PMID- 22036887 TI - Non-adjuvanted 2009 influenza A (H1N1)v vaccine in pregnant women: the results of a French prospective descriptive study. AB - In 2009, during the influenza A (H1N1)v pandemic, the French Health authorities recommended influenza immunisation for pregnant women because of the higher risk of serious influenza outcomes in that population. Thus, the non-adjuvanted inactivated influenza vaccine Panenza((r)) was administered to French women from the second trimester of pregnancy. Several studies suggest that inactivated seasonal influenza vaccines are safe during pregnancy but there are few data about the effects of new A (H1N1)vaccines (new antigen) on pregnant women. OBJECTIVE: The aim of the present prospective study was to describe pregnancy outcomes among women vaccinated with non-adjuvanted influenza vaccines in South Western France. METHODS: the study ran from November 2009 to February 2010 and included, on a voluntary basis, pregnant women who were vaccinated against A (H1N1) influenza in vaccination clinics or maternity wards. RESULTS: 569 pregnant women were monitored until delivery. Compared with the general population, the risks of maternal conditions, malformations and neonatal conditions were not statistically different. CONCLUSION: This study does not reveal any sign of safety concerns regarding the effects of the vaccine on pregnancy outcomes. PMID- 22036888 TI - Differential acetylcholinesterase inhibition of chlorpyrifos, diazinon and parathion in larval zebrafish. AB - Zebrafish are increasingly used for developmental neurotoxicity testing because early embryonic events are easy to visualize, exposures are done without affecting the mother and the rapid development of zebrafish allows for high throughput testing. We used zebrafish to examine how exposures to three different organophosphorus pesticides (chlorpyrifos, diazinon and parathion) over the first five days of embryonic and larval development of zebrafish affected their survival, acetylcholinesterase (AChE) activity and behavior. We show that at non lethal, equimolar concentrations, chlorpyrifos (CPF) is more effective at equimolar concentrations than diazinon (DZN) and parathion (PA) in producing AChE inhibition. As concentrations of DZN and PA are raised, lethality occurs before they can produce the degree of AChE inhibition observed with CPF at 300 nM. Because of its availability outside the mother at the time of fertilization, zebrafish provides a complementary model for studying the neurotoxicity of very early developmental exposures. PMID- 22036889 TI - Long-term mortality in patients diagnosed with Listeria monocytogenes meningitis: a Danish nationwide cohort study. AB - OBJECTIVES: To determine the long-term mortality, the causes of death and the incidence of cancer in listeria meningitis patients. METHODS: Nationwide, population-based cohort study including all adult patients diagnosed with listeria meningitis from 1977 to 2006 and alive 1 year after diagnosis, and an age-and gender-matched, population control cohort. Kaplan-Meier tables, Cox regression analysis and cumulative incidence function were used as outcome analyses. RESULTS: We identified 114 listeria meningitis patients and 1026 population controls. The adjusted mortality rate ratio (MRR) for listeria meningitis patients the first 5 years of follow-up was 2.35(95% confidence interval (CI) 1.60-3.45) thereafter the MRR was 0.93(95% CI: 0.56-1.55). Listeria meningitis patients had an increased risk of death due to cancer the first 5 years of follow-up, and in the same period patients above 50 years of age had a 2 fold increased risk of being diagnosed with cancer, thereafter the risks declined to that of the background population. CONCLUSIONS: The long-term mortality in adult patients diagnosed with listeria meningitis was increased the first 5 years of follow-up, mainly due to death from cancer, thereafter the mortality did not differ from the background population. To improve survival this patient population should be meticulously screened for predisposing conditions, mainly underlying malignant diseases. PMID- 22036890 TI - Ghrelin is involved in voluntary anorexia in Atlantic salmon raised at elevated sea temperatures. AB - Due to global and local climate changes, farmed salmon may experience periods of elevated sea temperatures. An experiment was conducted to examine endocrine and dietary effects of high sea temperatures in adult (2.0 kg) and sexually immature Atlantic salmon, Salmo salar L. Groups of salmon were exposed to 19 degrees C while others were kept as controls at 14 degrees C. The experiment lasted for 56 days, and fish were given iso-nitrogenous diets with either a normal (335 g kg( 1); L34) or a lower lipid level (298 g kg(-1); L30). Fish held at 19 degrees C had a reduction in the daily feed intake, growth and feed utilization of more than 50% compared to the controls. Fish at 19 degrees C retained little ingested fat, and high maintenance cost lead to depleted endogenous energy body reserves. Circulating ghrelin concentration and stomach ghrelin-1 and hypothalamus growth hormone secretagogue receptor 1a-like receptor (GHSR1a-LR) mRNA levels were significantly reduced in salmon at 19 degrees C. An increasing number of fish kept at 19 degrees C had empty gastrointestinal tract after 21 days (11-67%) and 56 days (56-100%), with the highest numbers in fish fed the L34 diet. We suggest that lower circulating ghrelin during negative energy homeostasis induce down regulation of GHSR1a-LR, neuropeptide Y, and anorexigenic factors at transcriptional levels in the hypothalamus, which over time lead to a voluntary anorexia development in adult salmon held at 19 degrees C. Reduction of feed intake and growth may be an important coping strategy for salmon during elevated temperatures. PMID- 22036891 TI - Host-defense peptides in skin secretions of African clawed frogs (Xenopodinae, Pipidae). AB - African clawed frogs of the Xenopodinae (Xenopus+Silurana) constitute a well defined system in which to study the evolutionary trajectory of duplicated genes and are a source of antimicrobial peptides with therapeutic potential. Allopolyploidization events within the Xenopodinae have given rise to tetraploid, octoploid, and dodecaploid species. The primary structures and distributions of host-defense peptides from the tetraploid frogs Xenopus borealis, Xenopus clivii, Xenopus laevis, Xenopus muelleri, "X. muelleri West", and Xenopus petersii may be compared with those from the octoploid frogs Xenopus amieti and X. andrei. Similarly, components in skin secretions from the diploid frog Silurana tropicalis may be compared with those from the tetraploid frog Silurana paratropicalis. All Xenopus antimicrobial peptides may be classified in the magainin, peptide glycine-leucine-amide (PGLa), caerulein-precursor fragment (CPF), and xenopsin-precursor fragment (XPF) families. However, the numbers of paralogs from the octoploid frogs were not significantly greater than the corresponding numbers from the tetraploid frogs. Magainins were not identified in skin secretions of Silurana frogs and the multiplicity of the PGLa, CPF, and XPF peptides from S. paratropicalis was not greater than that of S. tropicalis. The data indicate, therefore, that nonfunctionalization (gene silencing) has been the most common fate of antimicrobial peptide genes following polyploidization. While some duplicated gene products retain high antimicrobial potency (subfunctionalization), the very low activity of others suggests that they may be evolving towards a new biological role (neofunctionalization). CPF-AM1 and PGLa AM1 from X. amieti show potential for development into anti-infective agents for use against antibiotic-resistant gram-negative bacteria. PMID- 22036892 TI - Modeling extracellular electrical neural stimulation: from basic understanding to MEA-based applications. AB - Extracellular electrical stimulation of neural networks has been widely used empirically for decades with individual electrodes. Since recently, microtechnology provides advanced systems with high-density microelectrode arrays (MEAs). Taking the most of these devices for fundamental goals or developing neural prosthesis requires a good knowledge of the mechanisms underlying electrical stimulation. Here, we review modeling approaches used to determine (1) the electric potential field created by a stimulation and (2) the response of an excitable cell to an applied field. Computation of the potential field requires solving the Poisson equation. While this can be performed analytically in simple electrode-neuron configurations, numerical models are required for realistic geometries. In these models, special care must be taken to model the potential drop at the electrode/tissue interface using appropriate boundary conditions. The neural response to the field can then be calculated using compartmentalized cell models, by solving a cable equation, the source term of which (called activating function) is proportional to the second derivative of the extracellular field along the neural arborization. Analytical and numerical solutions to this equation are first presented. Then, we discuss the use of approximated solutions to intuitively predict the neuronal response: Either the "activating function" or the "mirror estimate", depending on the pulse duration and the cell space constant. Finally, we address the design of optimal electrode configurations allowing the selective activation of neurons near each stimulation site. This can be achieved using either multipolar configurations, or the "ground surface" configuration, which can be easily integrated in high-density MEAs. Overall, models highlighting the mechanisms of electrical microstimulation and improving stimulating devices should help understanding the influence of extracellular fields on neural elements and developing optimized neural prostheses for rehabilitation. PMID- 22036893 TI - CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. AB - Overwhelming evidence shows the quality of reporting of randomised controlled trials (RCTs) is not optimal. Without transparent reporting, readers cannot judge the reliability and validity of trial findings nor extract information for systematic reviews. Recent methodological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which are considered the gold standard for evaluating interventions because of their ability to minimise or avoid bias. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. It was first published in 1996 and updated in 2001. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have endorsed the CONSORT statement. The statement facilitates critical appraisal and interpretation of RCTs. During the 2001 CONSORT revision, it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports. A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement. After an expert meeting in January 2007, the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement. This update improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition, such as selective outcome reporting bias. This explanatory and elaboration document-intended to enhance the use, understanding, and dissemination of the CONSORT statement-has also been extensively revised. It presents the meaning and rationale for each new and updated checklist item providing examples of good reporting and, where possible, references to relevant empirical studies. Several examples of flow diagrams are included. The CONSORT 2010 Statement, this revised explanatory and elaboration document, and the associated website (www.consort-statement.org) should be helpful resources to improve reporting of randomised trials. PMID- 22036894 TI - Clinical implementation of a GPU-based simplified Monte Carlo method for a treatment planning system of proton beam therapy. AB - We implemented the simplified Monte Carlo (SMC) method on graphics processing unit (GPU) architecture under the computer-unified device architecture platform developed by NVIDIA. The GPU-based SMC was clinically applied for four patients with head and neck, lung, or prostate cancer. The results were compared to those obtained by a traditional CPU-based SMC with respect to the computation time and discrepancy. In the CPU- and GPU-based SMC calculations, the estimated mean statistical errors of the calculated doses in the planning target volume region were within 0.5% rms. The dose distributions calculated by the GPU- and CPU-based SMCs were similar, within statistical errors. The GPU-based SMC showed 12.30 16.00 times faster performance than the CPU-based SMC. The computation time per beam arrangement using the GPU-based SMC for the clinical cases ranged 9-67 s. The results demonstrate the successful application of the GPU-based SMC to a clinical proton treatment planning. PMID- 22036895 TI - HMGA-targeted phosphorothioate DNA aptamers increase sensitivity to gemcitabine chemotherapy in human pancreatic cancer cell lines. AB - Elevated high mobility group A (HMGA) protein expression in pancreatic cancer cells is correlated with resistance to the chemotherapy agent gemcitabine. Here, we demonstrate use of HMGA-targeted AT-rich phosphorothioate DNA (AT-sDNA) aptamers to suppress HMGA carcinogenic activity. Cell growth of human pancreatic cancer cells (AsPC-1 and Miapaca-2) transfected with AT-sDNA were monitored after treatment with gemcitabine. Significant increases in cell death in AT-sDNA transfected cells compared to non-AT-rich sDNA treated cells were observed in both cell lines. The data indicate the potential use of HMGA targeted DNA aptamers to enhance chemotherapy efficacy in pancreatic cancer treatment. PMID- 22036896 TI - Systemic use of tumor necrosis factor alpha as an anticancer agent. AB - Tumor necrosis factor-alpha (TNF-alpha) has been discussed as a potential anticancer agent for many years, however initial enthusiasm about its clinical use as a systemic agent was curbed due to significant toxicities and lack of efficacy. Combination of TNF-alpha with chemotherapy in the setting of hyperthermic isolated limb perfusion (ILP), has provided new insights into a potential therapeutic role of this agent. The therapeutic benefit from TNF-alpha in ILP is thought to be not only due to its direct anti-proliferative effect, but also due to its ability to increase penetration of the chemotherapeutic agents into the tumor tissue. New concepts for the use of TNF-alpha as a facilitator rather than as a direct actor are currently being explored with the goal to exploit the ability of this agent to increase drug delivery and to simultaneously reduce systemic toxicity. This review article provides a comprehensive overview on the published previous experience with systemic TNF-alpha. Data from 18 phase I and 10 phase II single agent as well as 18 combination therapy studies illustrate previously used treatment and dose schedules, response data as well as the most prominently observed adverse effects. Also discussed, based on recent preclinical data, is a potential future role of systemic TNF-alpha in combination with liposomal chemotherapy to facilitate increased drug uptake into tumors. PMID- 22036897 TI - ABC transporter efflux pumps: a defense mechanism against ivermectin in Rhipicephalus (Boophilus) microplus. AB - ATP-binding cassette (ABC) transporters are efflux transporters found in all organisms. These proteins are responsible for pumping xenobiotic and endogenous metabolites through extra- and intracellular membranes, thereby reducing cellular concentrations of toxic compounds. ABC transporters have been associated with drug resistance in several nematodes and parasitic arthropods. Here, the ability of ABC transporter inhibitors to enhance ivermectin (IVM) sensitivity was tested in larvae and adult females of Rhipicephalus (Boophilus) microplus. Larvae of susceptible and IVM-resistant tick populations were pre-exposed to sub-lethal doses of the ABC transporter inhibitors Cyclosporin A (CsA) and MK571, and subsequently treated with IVM in a Larval Packet Test (LPT). ABC transporter inhibition by both drugs significantly reduced the concentration for 50% lethality (LC(50)) values of four IVM-resistant populations but IVM sensitivity of a susceptible population remained unchanged. IVM sensitivity in adults was assessed through an artificial feeding assay. The addition of CsA to a blood meal substantially affected IVM toxicity in adult female ticks from a resistant population by reducing oviposition and egg viability, although it did not alter IVM toxicity in susceptible females. Three partial nucleotide sequences with similarity to ABC transporters were retrieved from the DFCI Boophilus microplus Gene Index (http://compbio.dfci.harvard.edu/index.html). Their transcriptional levels in the midgut of resistant and susceptible females were determined by quantitative PCR, showing that one of these sequences was significantly up regulated in IVM-resistant females and suggesting its participation in IVM detoxification. We believe this work reports the first known evidence for the participation of ABC transporters in IVM resistance in R. microplus. PMID- 22036900 TI - Project red and asthmapolis. PMID- 22036899 TI - Source of truth: where is it in your documentation? AB - In summary, a variety of documentation sources may affect reporting accuracy as well as bedside efficiency. the successful process to streamline documentation at HealthEast requires clinicians from the bedside, informatics staff, and the quality office to ensure an efficient and thoughtful implementation. As hospitals begin to address the HITECH guidelines for electronic reporting, current documentation infrastructure may provide opportunity for process improvement. Where is your source of truth? PMID- 22036898 TI - The Mannose Receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNgamma production. AB - In this study, infective larvae of the parasitic helminth Schistosoma mansoni were shown to contain a large number of glycosylated components specific for the Mannose Receptor (MR; CD206), which is an important pattern recognition receptor (PRR) of the innate immune system. MR ligands were particularly rich in excretory/secretory (E/S) material released during transformation of cercariae into schistosomula, a process critical for infection of the host. E/S material from carboxyfluorescein diacetate succinimidyl ester (CFDA-SE)-labelled cercariae showed enhanced binding by cells lines that over-express the MR. Conversely, uptake was significantly lower by bone marrow-derived macrophages (MPhi) from MR( /-) mice, although they were more active as judged by enhanced pro-inflammatory cytokine production and CD40 expression. After natural percutaneous infection of MR(-/-) mice with CFDA-SE-labelled parasites, there were fewer cells in the skin and draining lymph nodes that were CFDA-SE(+) compared with wild-type mice, implying reduced uptake and presentation of larval parasite antigen. However, antigen-specific proliferation of skin draining lymph node cells was significantly enhanced and they secreted markedly elevated levels of IFNgamma but decreased levels of IL-4. In conclusion, we show that the MR on mononuclear phagocytic cells, which are plentiful in the skin, plays a significant role in internalising E/S material released by the invasive stages of the parasite which in turn modulates their production of pro-inflammatory cytokines. In the absence of the MR, antigen-specific CD4(+) cells are Th1 biased, suggesting that ligation of the MR by glycosylated E/S material released by schistosome larvae modulates the production of CD4(+) cell specific IFNgamma. PMID- 22036901 TI - Improving informatics skills for clinicians, new foundation incorporates. PMID- 22036903 TI - 2011 Summer Institute in Nursing Informatics. PMID- 22036904 TI - AssignFit: a program for simultaneous assignment and structure refinement from solid-state NMR spectra. AB - AssignFit is a computer program developed within the XPLOR-NIH package for the assignment of dipolar coupling (DC) and chemical shift anisotropy (CSA) restraints derived from the solid-state NMR spectra of protein samples with uniaxial order. The method is based on minimizing the difference between experimentally observed solid-state NMR spectra and the frequencies back calculated from a structural model. Starting with a structural model and a set of DC and CSA restraints grouped only by amino acid type, as would be obtained by selective isotopic labeling, AssignFit generates all of the possible assignment permutations and calculates the corresponding atomic coordinates oriented in the alignment frame, together with the associated set of NMR frequencies, which are then compared with the experimental data for best fit. Incorporation of AssignFit in a simulated annealing refinement cycle provides an approach for simultaneous assignment and structure refinement (SASR) of proteins from solid-state NMR orientation restraints. The methods are demonstrated with data from two integral membrane proteins, one alpha-helical and one beta-barrel, embedded in phospholipid bilayer membranes. PMID- 22036905 TI - Promotion of cell proliferation and inhibition of ADCC by cancerous immunoglobulin expressed in cancer cell lines. AB - To explore the significance of cancerous immunoglobulin (Ig) in cancer cell growth, HeLa cervical cancer cells were stably transfected with small interfering RNA (siRNA) that specifically, efficiently and consistently silences the expression of heavy chain genes of all immunoglobulin isotypes. This stable cell line was used to examine cell viability, colony formation and tumor growth in athymic nude mice. The results of these experiments indicated that siRNA-mediated knockdown of cancerous Ig inhibited cell growth in vitro and suppressed tumor cell growth in immune-deficient nude mice in vivo. Similarly, this siRNA also inhibited the growth of MGC gastric cancer cells and MCF-7 breast cancer cells. Furthermore, the presence of cancerous Ig specifically reduced antibody-dependent cell-mediated cytotoxicity (ADCC) induced by an anti-human epithelial growth factor receptor (EGFR) antibody in a dose-dependent manner, suggesting that the cancerous Ig-Fc receptor interaction inhibits natural killer cell (or NK cell) effector function. The prevalent expression of Ig in human carcinomas and its capacity to promote growth and inhibit immunity might have important implications in growth regulation and targeted therapy for human cancers. PMID- 22036907 TI - Identification of novel missense mutations of the TGFBR3 gene in Chinese women with premature ovarian failure. AB - The aim of this study was to assess the association between human transforming growth factor beta receptor, type III (TGFBR3) and idiopathic premature ovarian failure (POF) in a Chinese population. A total of 112 Chinese women with idiopathic POF and 110 normal controls were examined. DNA samples prepared from blood leukocytes were used as templates for polymerase-chain reaction amplification of DNA fragments from TGFBR3. The gene fragments were sequenced. Web-based programs, including PolyPhen, Sorting Intolerant from Tolerant (SIFT), Prediction of Pathological Mutations (PMUT), ScanProsite and ClustalW2, were used to predict the potential functional and structural impacts of the missense variants of TGFBR3. A total of 11 novel variants were identified. Among them, six were found only in the POF patients. Two missense variants, p.E459G and p.P825L, which are conserved in primates, were predicted to have functional and structural impacts on the TGFBR3 protein. The other four variants (c.381+12A>C, c.2431-7A>G, p.S172S and p.C220C) were considered benign. However, further functional studies are necessary to confirm these findings. PMID- 22036906 TI - Guided delivery of adeno-associated viral vectors into the primate brain. AB - In this review, we discuss recent developments in the delivery of adeno associated virus-based vectors (AAV), particularly with respect to the role of axonal transport in vector distribution in the brain. The use of MRI-guidance and new stereotactic aiming devices have now established a strong foundation for neurological gene therapy to become an accepted procedure in interventional neurology. PMID- 22036908 TI - Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes. AB - The exchange of histones with protamines in sperm DNA results in sperm chromatin compaction and protection. Variations in sperm protamine expression are associated with male infertility. The aim of this study was to investigate relationships between DNA fragmentation, sperm protamines and assisted reproduction treatment. Semen and spermatozoa prepared by density-gradient centrifugation (DGC) from 73 men undergoing IVF and 24 men undergoing intracytoplasmic sperm injection (ICSI) were included in the study. Nuclear DNA fragmentation was assessed using the alkaline Comet assay and protamines were separated by acid-urea polyacrylamide gels. Sperm DNA fragmentation and protamine content (P1-DNA, P2-DNA, P1+P2-DNA) decreased in spermatozoa after DGC. Abnormally high and low P1/P2 ratios were associated with increased sperm DNA fragmentation. Couples with idiopathic infertility had abnormally high P1/P2 ratios. Fertilization rates and embryo quality decreased as sperm DNA fragmentation or protamines increased. Sperm DNA fragmentation was lower in couples achieving pregnancies after IVF, but not after ICSI. There was no correlation between protamine content (P1-DNA, P2-DNA, P1+P2-DNA) or P1/P2 ratios and IVF or ICSI pregnancies. Increased sperm DNA fragmentation was associated with abnormal protamination and resulted in lower fertilization rates, poorer embryo quality and reduced pregnancy rates. PMID- 22036909 TI - Development of quantitative computed-tomography-based strength indicators for the identification of low bone-strength individuals in a clinical environment. AB - The aim of this study was to develop quantitative computed-tomography (QCT)-based bone-strength indicators that highly correlate with finite-element (FE)-based strength. Transaxial QCT scans were obtained from 36 major, cadaveric, long bones (humerus, radius, femur and tibia) from 4 females and 2 males, 53 to 86 years old. These images were used to construct the FE models and to develop the QCT based bone strength indicators under every-day, simplified loading conditions. We have evaluated the performance of area-weighted (AW), density-weighted (DW) and modulus-weighted (MW) rigidity measures as well as popular strength indicators like section modulus (Z) and stress-strain index (SSI). We have also developed a novel strength metric, the centroid deviation, which analyzes the spatial distribution of the centroids along the length of the bone. The correlation results show that the MW polar moment of inertia and the MW moment of inertia are the two top-performers for all bones and loading conditions (average r>0.89). The MW centroid deviations correlated highly with the estimated load to fracture for all bones under compression (r>0.83), except for the humerus (r=0.67). Consistently DW or MW rigidity measures produced a statistically significant improvement in capturing bone strength compared to AW rigidity measures. As expected, MW rigidity measures showed a higher correlation with the FE-based fracture load than the DW rigidity measures; however, the improvement was not statistically significant. Through this study we present a short-list of useful QCT-based strength parameters that correlate well with FE-based fracture load. Although a few parameters perform reasonably well across most bones and loading conditions, a judicious assessment of bone strength should include multiple parameters evaluated at multiple critical locations in the long bones, with attention to the type of loading and bone type. PMID- 22036910 TI - Teriparatide and the risk of nonvertebral fractures in women with postmenopausal osteoporosis. AB - PURPOSE: In the Fracture Prevention Trial, the risks of any nonvertebral fracture (relative risk [RR] 0.65, P=0.04) and any fragility nonvertebral fracture (RR 0.47, P=0.02) were significantly reduced in the teriparatide 20 MUg/day (teriparatide) versus placebo group. The purpose of this analysis was to examine the efficacy of teriparatide versus placebo on a variety of other nonvertebral fracture outcomes. MATERIALS AND METHODS: The Fracture Prevention Trial was a double-blind trial of postmenopausal women with osteoporosis and vertebral fractures randomly assigned to teriparatide (N=541) or placebo (N=544) administered by daily self-injection for a median of 19 months and a median follow-up of 21 months. All patients received calcium and vitamin D supplementation. Reports of nonvertebral fractures were collected from patients at each visit and confirmed by review of a radiograph or written radiology report. Nonvertebral fractures were recorded for the following sites: distal radius/wrist, humerus, rib/clavicle, hip, ankle, distal foot, pelvis, or other. Pathological fractures and fractures of the face, skull, metacarpals, fingers and toes were excluded. Fractures were classified by investigators as fragility or traumatic fractures. The three endpoints considered were six nonvertebral sites (nonvert-6), a set of common nonvertebral fractures described in a Food and Drug Administration Guidance document for the treatment and prevention of postmenopausal osteoporosis (FDA), and a European Union major set (major) of nonvertebral fractures. RESULTS: For teriparatide versus placebo, the point estimates for the RR of nonvert-6 (RR 0.54, P=0.06; fragility RR 0.32, P=0.014), FDA (RR 0.60, P=0.15; fragility RR 0.38, P=0.05), and major (RR 0.52, P=0.02; fragility RR 0.38, P=0.02) nonvertebral fracture endpoints were smaller than for the all nonvertebral fracture endpoint. Lower RRs were observed when the outcomes were limited to fragility fractures, and significant reductions in traumatic nonvertebral fractures were not observed. CONCLUSION: In the Fracture Prevention Trial, the risk reduction for nonvertebral fracture in patients treated with teriparatide versus placebo depended on the set of nonvertebral fractures included in the analysis; lower RRs were observed for nonvertebral fractures most likely to be of osteoporotic origin. No significant reductions in traumatic nonvertebral fractures were observed. PMID- 22036912 TI - Topically administered Risedronate shows powerful anti-osteoporosis effect in ovariectomized mouse model. AB - We investigated the therapeutic effect of topical Risedronate (RIS) on a mouse model of estrogen-deficient osteoporosis. Fourteen-week-old female mice were ovariectomized and assigned to 4 groups: SHAM-operated (SHAM), OVX mice treated with vehicle (OVX-V), OVX mice treated with 0.2% RIS (OVX-0.2% RIS), and OVX-mice treated with 0.02% RIS (OVX-0.02% RIS). Topical samples containing RIS were prepared in 10% (w/w) polyethylene glycol (PEG, MW 400) and 80 MUg of sample was spread on the mice's mid-backs every 3 days for 5 weeks. Micro-CT analysis of femora demonstrated that OVX-0.2% RIS exhibited a 29% greater bone mineral density and 24% greater bone volume fraction than that of OVX-V group. Investigation of the trabecular bone in OVX-0.2% RIS revealed a 24% higher bone volume (BV/TV), 51% higher trabecular number (Tb.N), and 40% lower trabecular separation (Tb.Sp) compared to OVX-V mice. Additionally, bone phenotypes of tibiae were further confirmed by histological analysis. OVX-0.2% RIS group exhibited a 494% greater BV/TV, 464% less Tb.Sp, 81% greater active osteoclast surface (Oc.S/BS) and 26% less osteoclast number (N.Oc/BS) than that of OVX-V group. Collectively, these results indicated that topical delivery of RIS has powerful pharmaceutical effects on the prevention of osteoporosis and bone turnover. PMID- 22036911 TI - Altered plasma membrane dynamics of bone morphogenetic protein receptor type Ia in a low bone mass mouse model. AB - Bone morphogenetic proteins (BMPs) are growth factors that initiate differentiation of bone marrow stromal cells to osteoblasts and adipocytes, yet the mechanism that decides which lineage the cell will follow is unknown. BMP2 is linked to the development of osteoporosis and variants of BMP2 gene have been reported to increase the development of osteoporosis. Intracellular signaling is transduced by BMP receptors (BMPRs) of type I and type II that are serine/threonine kinase receptors. The BMP type I a receptor (BMPRIa) is linked to osteogenesis and bone mineral density (BMD). BMPRs are localized to caveolae enriched with Caveolin1 alpha/beta and Caveolin beta isoforms to facilitate signaling. BMP2 binding to caveolae was recently found to be crucial for the initiation of the Smad signaling pathway. Here we determined the role of BMP receptor localization within caveolae isoforms and aggregation of caveolae as well as BMPRIa in bone marrow stromal cells (BMSCs) on bone mineral density using the B6.C3H-6T as a model system. The B6.C3H-6T is a congenic mouse with decreased bone mineral density (BMD) with increased marrow adipocytes and decreased osteoprogenitor proliferation. C57BL/6J mice served as controls since only a segment of Chr6 from the C3H/HeJ mouse was backcrossed to a C57BL/6J background. Family of image correlation spectroscopy was used to analyze receptor cluster density and co-localization of BMPRIa and caveolae. It was previously shown that BMP2 stimulation results in an aggregation of caveolae and BMPRIa. Additionally, BMSCs isolated from the B6.C3H-6T mice showed a dispersion of caveolae domains compared to C57BL/6J. The aggregation of BMPRIa that is necessary for signaling to occur was inhibited in BMSCs isolated from B6.C3H-6T. Additionally, we analyzed the co-localization of BMPRIa with caveolin-1 isoforms. There was increased percentage of BMPRIa co-localization with caveolae compared to C57BL/6J. BMP2 stimulation had no effect on the colocalization of BMPRIa with caveolin-1. Disrupting caveolae initiated Smad signaling in the isolated BMSCs from B6.C3H-6T. These data suggest that in congenic 6T mice BMP receptors aggregation is inhibited causing an inhibition of signaling and reduced bone mass. PMID- 22036913 TI - Semi-continuous photo-fermentative H2 production by Rhodobacter sphaeroides: effect of decanting volume ratio. AB - In this study, a semi-continuous operation of photo-fermentative H2-producing reactor was attempted at various decanting volume ratios (DVR, decanting volume per day/total working volume, %), ranging 30-70%, using Rhodobacter sphaeroides KD131. H2 production was not efficient with showing low H2 yields of 0.2 and 0.5 mol H2/mol succinate(added) at 30% and 40% DVR, respectively. The low performance ascribed to the fact that over 70% of substrate electrons were diverted towards cell growth under these conditions. Meanwhile, cell growth was limited at DVR>=50%; therefore, higher H2 yields (>2.0 mol H2/mol succinateadded) were observed. Both the highest H2 yield of 3.7 mol H2/mol succinateadded and production rate of 1494 mL H2/L-reactor/d were achieved at 60% DVR. The content of soluble microbial products (SMPs) was measured, which accounted for 3-15% of substrate electrons. It was found that the largest (65-75%) portion of SMPs comprised low molecular-weight (<3 kDa). PMID- 22036914 TI - Optimization of a free-fall reactor for the production of fast pyrolysis bio-oil. AB - A central composite design of experiments was performed to optimize a free-fall reactor for the production of bio-oil from red oak biomass. The effects of four experimental variables including heater set-point temperature, biomass particle size, sweep gas flow rate and biomass feed rate were studied. Heater set-point temperature ranged from 450 to 650 degrees C, average biomass particle size from 200 to 600 MUm, sweep gas flow rate from 1 to 5 sL/min and biomass feed rate from 1 to 2 kg/h. Optimal operating conditions yielding over 70 wt.% bio-oil were identified at a heater set-point temperature of 575 degrees C, while feeding red oak biomass sized less than 300 MUm at 2 kg/h into the 0.021 m diameter, 1.8m tall reactor. Sweep gas flow rate did not have significant effect on bio-oil yield over the range tested. PMID- 22036915 TI - President's perspective: the neurology section's strategic plan-first step. PMID- 22036916 TI - Serotonin-2A receptor and catechol-O-methyltransferase polymorphisms in panic disorder. AB - Catechol-O-methyltransferase (COMT) and serotonin receptor 2A (5HTR2A) polymorphisms have been investigated for their possible role in panic disorder (PD). The aim of this study was to investigate the genotype distribution of the COMT val158met and 5HTR2A 102T/C polymorphisms in PD. COMT val158met is a polymorphism at codon 158 that results in variations in COMT enzymatic activity with high- (H) and low-activity (L) alleles. The 5HTR2A 102T/C polymorphism comprises a T-to-C mutation at position 102. The effects of symptom severity, gender, and age of onset were also investigated. The participants were 105 outpatients with PD and 130 controls. The severity of the symptoms of PD was assessed by the Panic and Agoraphobia Scale (PAS). Polymorphisms of the 5HTR2A and COMT genes were identified using polymerase chain reaction and restriction fragment length polymorphism analysis. A significant relationship was found between the COMT Val158Met polymorphism and PD. No significant differences were found in genotype distributions or allele frequencies of the 5HTR2A polymorphisms between the PD and control groups. There were no significant relationships between the COMT and 5HTR2A polymorphisms and age of onset, gender, presence of agoraphobia, or PAS scores in the PD group (p>0.05). PMID- 22036917 TI - Long-term efficacy and safety of gabapentin enacarbil in Japanese restless legs syndrome patients. AB - Several short- and long-term studies conducted in Europe/North America have demonstrated good efficacy and tolerability of 600-1800 mg gabapentin enacarbil (GEn). However, no studies have evaluated the efficacy of long-term treatment with GEn in Asian patients. Therefore, the objective of this study was to evaluate the efficacy and safety of long-term treatment with GEn in Japanese patients with restless legs syndrome (RLS) in a multicenter open-label study. RLS patients aged 20-80 years were allocated to receive oral GEn 1200 mg/day for a treatment period of 52 weeks. International Restless Legs Syndrome Scale (IRLS) score, investigator- and patient-rated Clinical Global Impression (CGI) scores, Pittsburgh Sleep Quality Index (PSQI) total scores and subscores, and short form (SF)-36 subscores were assessed, and adverse events (AEs) were monitored. In 181 patients (mean age, 54.9+/-12.2 years; BMI, 23.0+/-2.6 kg/m2) IRLS score decreased from 24.4+/-0.4 at baseline to 6.3+/-0.6 at week 52, with a reduction of -18.0+/-0.6. The IRLS responder rate was 80.3% at week 52. ICGI and PCGI responder rates were 87.1% and 87.1%, respectively. PSQI and SF-36 also showed significant improvements. AEs were reported in 96.2% of patients but remained mild-to-moderate in nearly all the cases. Serious AEs occurred in 1.6%. Dizziness and somnolence were noted in 46.2% and 41.2% of patients, respectively, and mostly occurred during the first 4 weeks. No episodes of augmentation were reported. In conclusion, long-term treatment with GEn improved RLS symptoms as well as investigator- and patient-reported outcomes in Japanese patients with moderate-to-severe RLS, with an acceptable safety profile. Randomized, double blind, placebo/active-controlled trials are desirable to confirm these preliminary results. PMID- 22036918 TI - Aga1, the first alpha-Galactosidase from the human bacteria Ruminococcus gnavus E1, efficiently transcribed in gut conditions. AB - Differential gene expression analysis was performed in monoxenic mice colonized with Ruminococcus gnavus strain E1, a major endogenous member of the gut microbiota. RNA arbitrarily primed-PCR fingerprinting assays allowed to specifically detect the in vivo expression of the aga1 gene, which was further confirmed by RT-PCR. The aga1 gene encoded a protein of 744 residues with calculated molecular mass of 85,207 Da. Aga1 exhibited significant similarity with previously characterized alpha-Galactosidases of the GH 36 family. Purified recombinant protein demonstrated high catalytic activity (104 +/- 7 U mg(-1)) and efficient p-nitrophenyl-alpha-d-galactopyranoside hydrolysis [k(cat)/K(m) = 35.115 +/- 8.82 s(-1) mM(-1) at 55 degrees C and k(cat)/K(m) = 17.48 +/- 4.25 s( 1) mM(-1) at 37 degrees C]. PMID- 22036919 TI - Heading but not path or the tau-equalization strategy is used in the visual control of steering toward a goal. AB - The visual strategies for the control of steering toward a goal include aligning one's instantaneous direction of travel (i.e., heading; J. J. Gibson, 1950) or the future path (J. P. Wann & D. K. Swapp, 2000) specified by optic flow with the target, equating the time to closure of the target-heading angle with the time to passage of the target (tau equalization, B. Fajen, 2001), or using the target egocentric direction and steering to center the target in the straight ahead or cancel the target optical drift (S. K. Rushton, J. M. Harris, M. Lloyd, & J. P. Wann, 1998). Supporting evidences for the use of these strategies in guiding steering or walking toward a goal were reported, but no consensus has been reached. In this study, by presenting participants with displays in which target egocentric direction was fixed and thus unavailable for steering to force participants to rely on information from optic flow for the control of self motion, we systematically examined the use of the optic flow-based strategies in the visual control of steering toward a goal. We found that participants steered to align their heading with the target, supporting the use of the heading strategy. We found no evidence to support the use of the path or the tau equalization strategy in the visual control of steering toward a goal. PMID- 22036920 TI - The newly identified anorexigenic adipokine nesfatin-1 in hemodialysis patients: Are there associations with food intake, body composition and inflammation? AB - Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-alpha and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16+/-0.07ng/mL) and healthy subjects (0.17+/-0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia. PMID- 22036924 TI - Human platelet antigen 1a epitopes are dependent on the cation-regulated conformation of integrin alpha(IIb)beta(3) (GPIIb/IIIa). AB - BACKGROUND: The HPA-1a (Leu(33)) polymorphism of platelet integrin alphaIIbbeta3 is the target of alloantibodies in 70-80% cases of neonatal alloimmune thrombocytopenia (NAIT) in Caucasians and reliable detection of these antibodies is essential for appropriate clinical management. However, the ability to detect such antibodies is highly variable between laboratories and, in a number of clinical cases where there is a HPA-1 genotype mismatch between mother and neonate, HPA-1a antibodies are undetectable. Furthermore, some studies have not shown a consistent relationship between maternal anti-HPA-1a level and neonatal platelet count. Since the integrity and conformation of the alphaIIbbeta3 complex are dependent on divalent cations, we investigated whether HPA-1a epitope integrity and/or conformation might be affected by the presence of the cation chelator EDTA in patient samples or in assay buffers, thus providing a possible explanation for the variable sensitivity of current assays. PRINCIPLE FINDINGS: Exposure of the alphaIIbbeta3 complex to EDTA resulted in reduced reactivity of three anti-HPA-1a mAbs (B2, 19-7 and 23-15). More significantly, cation chelation adversely affected detection of polyclonal anti-HPA-1a, not only in the platelet immunofluorescence assay, where alloantibody binding was reduced compared to control platelets (mean MFI reduction 44.5%, range 17.3-69.7%, n=4), but also in the commonly used monoclonal antibody specific immobilisation of platelet antigens assay (MAIPA) where both alloantibody and monoclonal capture antibody binding were reduced (mean OD reduction 82.8%, range 68.3-96.6%, n=9). CONCLUSIONS: These data show that HPA-1a antibodies recognise epitopes on alphaIIbbeta3 that are sensitive to EDTA treatment and that cation chelation grossly reduces the sensitivity of the MAIPA assay by diminishing not only HPA-1a alloantibody binding but also 'capture' monoclonal antibody binding. These findings may, in part, explain the current variability in antibody measurement and will guide the development of more sensitive tests for anti-integrin antibodies in NAIT and other conditions. PMID- 22036925 TI - An immunochemical method for detection and analysis of changes in methylome. AB - DNA methylation is an important epigenetic modification involved in the ability of an organism to respond to stress and adaptation. It has been implicated in development, differentiation, oncogenesis, chromatin remodelling, nutrigenomics, and appears to play a pivotal role in many regulatory and adaptive functions. It is therefore important to analyze the status of DNA methylation and its changes under various developmental, carcinogenic, pharmacological, and environmental conditions. In this report we describe an immunochemical method for the detection of genome wide DNA methylation and its alterations under various conditions along with the analysis of DNA methyltransferase activity. The ability of this approach to detect and provide a map of methylomic changes in a genome facilitates assessment of various agents and conditions which can alter this important epigenetic signal. This experimental system permits rapid evaluation of potential target genes which would be modulated by DNA methylation changes and thus the gene networks that govern the processes. PMID- 22036926 TI - Factors affecting the use of a realtime telemetry system in emergency medical services. AB - We investigated the factors that affected the use of a realtime telemetry system (RTS) in emergency ambulances. During the study, a total of 7144 patients were transported to a hospital in the city of Wonju via ambulance. In 466 of these cases (7%), the Emergency Medical Technician (EMT) used the RTS. Based on the Elaboration Likelihood Model, we extracted variables from the run records, such as the qualifications of the EMT, level of the patient's consciousness and the transport time. The results indicated that EMTs with higher levels of expertise were more likely to use the RTS when the level of patient consciousness was low, regardless of transport time. Conversely, EMTs with low levels of expertise were more likely to use the RTS when the transport time from scene to hospital was long and were less likely to use the RTS when the transport time was short. There appear to be several ways of improving RTS usage in the pre-hospital situation. PMID- 22036927 TI - The added value of video for consultations in telemedicine for minor injuries work. AB - We examined the decisions made about transfer of patients with minor injuries, when telemedicine support was provided to the remote nurses in two different ways: the telemedicine doctor either used a video link, or a telephone call with viewing of digital X-ray images (a low resolution version of Picture Archiving and Communications Systems [PACS]). A quasi-randomized study design was used, with a panel of 20 emergency medicine doctors who independently reviewed previously-stored consultations using the two modalities. In total, 60 case reviews were conducted during five sessions, representing 33 different cases from the routine workload of Minor Treatment Centres in Scotland. More experienced doctors transferred fewer patients than less experienced doctors. The proportion of patients transferred was higher when PACS was used than when video was used in most of the cases. A mixed effects logistic regression model was fitted to the data. The estimated odds for patient transfer were 56% lower when video was used instead of PACS (odds ratio 0.44, 95% confidence interval 0.20, 0.93). Although the cost implications are not yet known, video support for local decision-making should remain the preferred method of telemedicine for minor injuries work. PMID- 22036928 TI - Teleconsultation: changes in technology and costs over a 12-year period. AB - In our previous study, in 1997, we evaluated the cost of teleconsultations in a primary care centre compared with the cost of the conventional alternative, travelling to the hospital. The results showed that teleconsultations were cheaper than patient travel when the annual workload was more than 110 patients in ophthalmology and 115 patients in dermatology. Using the same method of analysis for 2009 data showed that cost savings would occur if the annual workload was 20 patients in ophthalmology and 17 patients in dermatology. The main differences between the two studies are the reduced cost of the technology (which was based on PCs in 2009) and the increased cost of staff. Both studies show that teleconsultations can be cost-effective in a relatively small health centre. The cost of technology continues to decrease, although the other costs in our break-even analysis continue to increase. However, the usability of technology continues to improve, and this will make telemedicine a more attractive alternative in the future. PMID- 22036929 TI - Combined humic acid adsorption and enhanced Fenton processes for the treatment of naphthalene dye intermediate wastewater. AB - In this work, an humic acid adsorption with an enhanced Fenton oxidation was employed to treat the real effluent originating from the 1-diazo-2-naphthol-4 sulfonic acid (1,2,4-Acid) production plant. In a first step, humic acid with MgSO(4) was selected as adsorbent and precipitant for physicochemical pretreatment, the synergetic effect had led to 39% of COD removal and 89% of colour removal. A multi-staged Fenton oxidation process with inner circulation was introduced subsequently. The TOC, COD, 1,2,4-Acid, NH(4)(+)-N, SS and colour were reduced from 3024 mg/L, 12,780 mg/L, 9103 mg/L, 110 mg/L, 240 mg/L and 25,600 (multiple) to 46 mg/L, 210 mg/L, 21 mg/L, 16 mg/L, 3 mg/L and 25 through the combined process, respectively. Hydrogen peroxide consumed per kg COD had saved up to 36% when two-staged Fenton process with inner circulation (flow-back to influent ratio: 3) was applied. Influence of H(2)O(2) concentration, flow-back to influent ratio and staged Fenton mode were investigated in detail in order to find out the optimal operating parameters. The kinetics of 1,2,4-Acid degradation by two-staged Fenton process was investigated. The evolution of the main intermediates during the degradation process was conducted using the LC-(ESI)-TOF MS technique, and the results showed a staged degradation pathway from the ring opening of naphthalene compounds to the formation of benzene compounds and carboxyl acids. The combined process had been proved effective in both technical and economic aspects. PMID- 22036930 TI - Biodegradation of ciprofloxacin in water and soil and its effects on the microbial communities. AB - While antibiotics are frequently found in the environment, their biodegradability and ecotoxicological effects are not well understood. Ciprofloxacin inhibits active and growing microorganisms and therefore can represent an important risk for the environment, especially for soil microbial ecology and microbial ecosystem services. We investigated the biodegradation of (14)C-ciprofloxacin in water and soil following OECD tests (301B, 307) to compare its fate in both systems. Ciprofloxacin is recalcitrant to biodegradation and transformation in the aqueous system. However, some mineralisation was observed in soil. The lower bioavailability of ciprofloxacin seems to reduce the compound's toxicity against microorganisms and allows its biodegradation. Moreover, ciprofloxacin strongly inhibits the microbial activities in both systems. Higher inhibition was observed in water than in soil and although its antimicrobial potency is reduced by sorption and aging in soil, ciprofloxacin remains biologically active over time. Therefore sorption does not completely eliminate the effects of this compound. PMID- 22036931 TI - Identification of in vivo protein phosphorylation sites in human pathogen Schistosoma japonicum by a phosphoproteomic approach. AB - Schistosome is the causative agent of human schistosomiasis and related animal disease. Reversible protein phosphorylation plays a key role in signaling processing that are vital for a cell and organism. However, it remains to be undercharacterized in schistosomes. In the present study, we characterized in vivo protein phosphorylation events in different developmental stages (schistosomula and adult worms) of Schistosoma japonicum by using microvolume immobilized metal-ion affinity chromatography (IMAC) pipette tips coupled to nanoLC-ESI-MS/MS. In total, 127 distinct phosphorylation sites were identified in 92 proteins in S. japonicum. A comparison of the phosphopeptides identified between the schistosomula and the adult worms revealed 30 phosphoproteins co detected in both of the two worms. These proteins included several signal molecules and enzymes such as 14-3-3 protein, cysteine string protein, heat shock protein 90, epidermal growth factor receptor pathway substrate 8, proliferation associated protein 2G4, peptidyl-prolyl isomerase G, phosphofructokinase and thymidylate kinase. Additionally, the phosphorylation sites were examined for phosphorylation specific motif and evolutionarily conservation. The study represents the first attempt to determine in vivo protein phosphorylation in S. japonicum by using a phosphoproteomic approach. The results by providing an inventory of phosphorylated proteins may facilitate to further understand the mechanisms involved in schistosome development and growth, and then may result in the development of novel vaccine candidates and drug targets for schistosomiasis control. PMID- 22036932 TI - Anterior pelvic soft tissue thickness influences acetabular cup positioning with imageless navigation. AB - The purpose of this study was to investigate acetabular component position after total hip arthroplasty correlating both version and inclination to anterior pelvic soft tissue thickness. Thirty patients with a mean age of 66.5 +/- 14 (28 87) years and an average body mass index of 30.04 +/- 4.6 were included. The same surgeon operated on all 30 patients, using an anterolateral approach in a supine position and an imageless navigation system. Postoperative assessment of cup inclination, cup anteversion, and soft tissue thickness was measured by an independent research associate using computed tomographic scans. Pearson's moment correlations did not reveal any significant relationships between body mass index, soft tissue thickness, final intraoperative, or postoperative cup position. Anterior soft tissue thickness had no significant effect on the accuracy of acetabular cup positioning. PMID- 22036933 TI - Classification and management of the unstable total hip arthroplasty. AB - Seventy-five total hip arthroplasty revisions for instability were classified into 6 primary etiologies: I, acetabular component malposition; II, femoral component malposition; III, abductor deficiency; IV, impingement; V, late wear; or VI, unresolved etiology. The most common etiologies were cup malposition (type I; 33%) and abductor deficiency (type III; 36%). At a mean of 35.3 months, 11 redislocations occurred (14.6%). Acetabular revisions were protective against redislocation (P < .015). The number of previous operations (P = .0379) and previously failed constrained liners (P < .02) were risk factors for failure. Tripolar constrained liners demonstrated improved survivorship vs locking ring types (P < .02); cemented constrained liners failed more often than modular constrained liners (P < .0018). The highest risk of failure was in patients with abductor insufficiency with revisions for other etiologies having a success rate of 90%. PMID- 22036934 TI - Xanthurenic acid is an endogenous substrate for the silkworm cytosolic sulfotransferase, bmST1. AB - Sulfotransferase enzymes are known to regulate physiologically active substances such as steroids and catecholamines in mammals. Although invertebrates also express sulfotransferases, their biological function is mostly unclear. In a previous study, we reported that 4-nitrocatechol and the gallete ester are substrates for the silkworm sulfotransferase bmST1. The K(m) of bmST1 for these substrates is high. However, endogenous substrates of bmST1 have not yet been determined. We therefore investigated endogenous bmST1 substrates and carried out a detailed expression profile analysis of bmST1. We found that xanthurenic acid, a tryptophan metabolite, is a possible endogenous substrate of bmST1. The K(m) of bmST1 for xanthurenic acid is low, in the MUM range, which is lower than that for previously reported substrates. Additionally, xanthurenic acid is a tryptophan metabolite that characteristically shows toxicity in vivo. High dose administration of xanthurenic acid resulted in inhibition of cuticular biosynthesis. The expression of the bmST1 gene reached a maximal level in the Malpighian tubule at the 4th molting stage, when amino acid metabolism might be activated. Our results suggest that bmST1 plays a role in detoxification of xanthurenic acid in the silkworm. PMID- 22036935 TI - Events temporarily associated with anti-influenza A (H1N1) vaccination in Mexico. AB - BACKGROUND AND AIMS: In Mexico from December 2009 to June 2010, 45,490,501 doses of the vaccine against the influenza virus were administered; 27,048,330 of those corresponded to influenza A (H1N1) and 18,442,171 to seasonal influenza. Therefore, the assessment of events temporarily associated with vaccination (ETAV) is mandatory. METHODS: The database corresponding to the ETAV associated with influenza (A [H1N1] and seasonal) immunization reported between December 2009 and June 2010 was analyzed. Patients who displayed at least one ETAV with one of the following schedules were included: A) influenza A (H1N1) vaccine, B) seasonal influenza vaccine, C) influenza A (H1N1) vaccine and seasonal influenza vaccine. RESULTS: A total of 597 ETAVs were reported. The 20- to 49-year-old age group was the most affected one (52.9%). The ETAV notification rate for influenza A (H1N1) vaccination was 1.41/100,000 applied doses vs. 0.74/100,000 applied doses corresponding to the seasonal influenza vaccination. Fifty seven events were considered serious (14 corresponded to Guillain-Barre syndrome) and these were considered coincidental unrelated events. CONCLUSIONS: There is no evidence of an increased rate of Guillain-Barre Syndrome with respect to the cases expected in the general population. PMID- 22036936 TI - High level of PTEN expression is associated with low-grade liver metastasis and satisfactory patient survival in pancreatic cancer. AB - BACKGROUND AND AIMS: We investigated PTEN expression in primary pancreatic cancer and pancreatic cancer liver metastasis in order to evaluate the interrelationship between PTEN expression and clinicopathological characteristics of pancreatic cancer patients with and without liver metastasis. METHODS: Eighty five primary pancreatic cancer specimens without liver metastasis were analyzed as controls. Eighty seven pancreatic cancer specimens and homologous liver metastasis specimens were investigated immunohistochemically, and the correlation between immunohistochemical findings and clinicopathological factors was investigated. RESULTS: A strong PTEN expression was observed in 52 (61.2%) specimens from patients without liver metastasis. In contrast, only 26 (29.9%) specimens were observed in patients with liver metastasis. A strong PTEN expression was apparently associated with low-grade lymph node metastasis (p <0.05) and TNM stage (p <0.05). PTEN expression in patients without liver metastasis was apparently stronger than that with liver metastasis. In addition, among patients with liver metastasis, the 5-year survival rate was markedly higher in patients with strong PTEN expression compared to those with weak PTEN expression. CONCLUSIONS: Our results suggest that a high level of PTEN expression is associated with low-grade liver metastasis and satisfactory patient survival in pancreatic cancer. The diagnostic evaluation of PTEN expression may provide valuable prognostic information to aid treatment strategies for pancreatic cancer patients. PMID- 22036937 TI - Emergency departments in The Netherlands. AB - Emergency medicine in The Netherlands is faced with an increasing interest by politicians and stakeholders in health care. This is due to crowding, increasing costs, criticism of the quality of emergency care, restructuring of out-of-hours services in primary care and the introduction of a training programme for emergency physicians in 2000. A comprehensive search was conducted of published research, policy reports and updated Dutch websites on acute care. Publications were included in this review if these referred to emergency care, including emergency departments (ED), general practitioner (GP) cooperatives and emergency medical services in The Netherlands and were written in English or Dutch. The literature search identified 14 eligible papers. The manual search identified 11 additional papers. Seven reports and two PhD theses were also included. Given the lack of relevant empirical research the review was liberal in its inclusion, but the analysis focused on research when available. ED in The Netherlands are in different stages of development. However, it is obvious that the presence of emergency physicians is increasing and more ED will be staffed by emergency physicians. Although this seems an important step, it does not necessarily imply a good position of the emergency physician in the ED. What the characteristics of the future patient of the Dutch ED will be is dependent on the development of different ED levels of care and GP cooperatives. The lack of empirical research also points out the need for research on quality of care in Dutch ED. PMID- 22036938 TI - Airway management in unconscious non-trauma patients. AB - BACKGROUND: Tracheal intubation is recommended in unconscious trauma patients to protect the airway from pulmonary aspiration of gastric contents and also to ensure ventilation and oxygenation. Unconsciousness is often defined as a Glasgow Coma Scale (GCS) score below 9. In non-trauma patients, however, there are no such firm recommendations regarding airway management and the GCS score may be less useful. The aim of this study was to describe the authors' experience with airway management in unconscious non-trauma patients in the prehospital setting with a physician-manned Mobile Emergency Care Unit (MECU). The main focus of the study was on the need for subsequent tracheal intubation during hospitalisation after initial treatment. METHODS: The study was based on an analysis of data prospectively collected from the MECU database in Copenhagen, Denmark. All unconscious (GCS scores below 9) non-trauma patients registered in the database during 2006 were included. The ambulance patient charts and medical records were scrutinised to assess outcome and the need for tracheal intubation during the first 24 h after admittance into hospital. RESULTS: A total of 557 unconscious non-trauma patients were examined and 129 patients (23%) were tracheally intubated by the MECU physician before or during transport to the hospital. Intubation was done in most patients with cardiac arrest, severe stroke or respiratory failure. Of the remaining 428 patients, 364 (85%) regained consciousness before being transported to the hospital, whereas 64 patients remained unconscious during transport and 12 (19%) of these were intubated in the emergency department. CONCLUSIONS: The majority of unconscious non-trauma patients were not intubated in the prehospital setting. Unconscious non-trauma patients may not all need tracheal intubation before being transferred to hospital. PMID- 22036939 TI - Stem cells from foreign body granulation tissue accelerate recovery from acute kidney injury. AB - BACKGROUND: In previous studies, we obtained mesenchymal stem cells called granulation tissue stem cells (GTSC) from a regenerating granulation tissue created by placing a foreign body in the subcutaneous tissue of rats. Here, we used GTSC to ameliorate ischemia/reperfusion-induced acute kidney injury (AKI) in rats. METHODS: In two groups of Fischer rats, we induced ischemia/reperfusion injury. Group 1 (treated rats) received one intravenous injection of GTSC 3 h after injury; Group 2 (control rats) received vehicle. Both groups were subsequently studied by renal function tests, kidney histology and immunohistochemistry. RESULTS: At 24 and 48 h after injury, plasma creatinine and blood urea nitrogen were significantly lower in the treated rats as compared to control rats. The levels remained low and declined to near baseline levels by Day 4 in the treated group. At the cortico-medullary region, the treated rats showed significantly higher renal tubular cell proliferation and less tubular cell apoptosis. Histological analysis of the kidney for tubular dilatation, necrosis, congestion and casts was not significantly different in the two groups. To understand the mechanism of the GTSC effect, messenger RNA levels of several growth and immune modulatory factors were quantified in cultured GTSC and compared with those in cultured glomerular epithelial cell (GEC; a non-stem cell line). GTSC had 2- to 8-fold higher expression of FGF2, HGF, IGF-1, vascular endothelial growth factor (growth factors) and IL-4, IL-6 (anti-inflammatory factors) than GEC. CONCLUSIONS: Administration of GTSC accelerates recovery in rats with ischemia/reperfusion-induced AKI. This effect may be mediated by the paracrine action of growth and immune-suppressive factors secreted by these cells. PMID- 22036940 TI - Early treatment with everolimus exerts nephroprotective effect in rats with adriamycin-induced nephrotic syndrome. AB - BACKGROUND: Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and excessive fluid retention. The effects of early versus late treatment with low or high doses of oral everolimus, a mammalian target of rapamycin inhibitor, on proteinuria in NS have not been previously described. METHODS: The effects of early treatment (2 days prior to NS induction) versus late treatment (beginning 2 weeks following the establishment of NS) with a low (20 mg/L) or high (100 mg/L) dose of everolimus for 5-7 weeks on proteinuria and nephrin/podocin abundance were assessed in male adult SD rats with adriamycin induced NS. RESULTS: Adriamycin caused a significant increase in daily and cumulative proteinuria throughout the experimental period. Early, and to a lesser extent late treatment, with a low dose of everolimus, significantly decreased both daily and cumulative proteinuria and improved renal function. The anti proteinuric effects of low-dose everolimus were associated with restoration of the disruptive glomerular nephrin/podocin abundance. In contrast, administration of a high dose of everolimus resulted in a decrease in proteinuria in NS rats, subsequently to deterioration of renal function. CONCLUSIONS: Early, and to a lesser extent late treatment, with a low but not a high dose of everolimus is effective in reducing proteinuria in nephrotic rats. The mechanism may be via nephrin/podocin protection. PMID- 22036941 TI - Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD. AB - BACKGROUND: Secondary hyperparathyroidism (sHPT) represents an adaptive response to progressively impaired control of calcium, phosphorus and vitamin D in chronic kidney disease (CKD). It is characterized by parathyroid hyperplasia and excessive synthesis and secretion of parathyroid hormone (PTH). Parathyroid hyperplasia in uremic rats can be prevented by calcium-sensing receptor (CaSR) activation with the calcimimetic cinacalcet (Sensipar(r)/Mimpara(r)); however, it is unknown, how long the effects of cinacalcet persist after withdrawal of treatment or if cinacalcet is efficacious in uremic rats with established sHPT. METHODS: We sought to determine the effect of cinacalcet discontinuation in uremic rats and whether cinacalcet was capable of influencing parathyroid hyperplasia in animals with established sHPT. RESULTS: Discontinuation of cinacalcet resulted in reversal of the beneficial effects on serum PTH and parathyroid hyperplasia. In rats with established sHPT, cinacalcet decreased serum PTH and mediated regression of parathyroid hyperplasia. The cinacalcet mediated decrease in parathyroid gland size was accompanied by increased expression of the cyclin-dependent kinase inhibitor p21. Prevention of cellular proliferation with cinacalcet occurred despite increased serum phosphorus and decreased serum calcium. CONCLUSIONS: The animal data provided suggest established parathyroid hyperplasia can be reversed by modulating CaSR activity with cinacalcet and that continued treatment may be necessary to maintain reductions in PTH. PMID- 22036942 TI - Social adaptability index predicts kidney transplant outcome: a single-center retrospective analysis. AB - BACKGROUND: Social adaptability index (SAI) is the composite index of socioeconomic status based upon employment status, education level, marital status, substance abuse and income. It has been used in the past to define populations at higher risk for inferior clinical outcomes. The objective of this retrospective study was to evaluate the association of the SAI with renal transplant outcome. METHODS: We used data from the clinical database at the Beth Israel Deaconess Medical Center Transplant Institute, supplemented with data from United Network for Organ Sharing for the years 2001-09. The association between SAI and graft loss and recipient mortality in renal transplant recipients was studied using Cox model in the entire study population as well as in the subgroups based on age, race, sex and diabetes status. RESULTS: We analyzed 533 end-stage renal disease patients (mean age at transplant 50.8 +/- 11.8 years, 52.2% diabetics, 58.9% males, 71.1% White). Higher SAI on a continuous scale was associated with decreased risk of graft loss [hazard ratio (HR) 0.89, P < 0.05, per 1 point increment in the SAI] and decreased risk of recipient mortality (HR 0.84, P < 0.01, per 1 point increment in the SAI). Higher SAI was also significantly associated with decreased risk for graft loss/recipient mortality in some study subgroups (age 41-65 years, males, non-diabetics). CONCLUSIONS: SAI has an association with graft and recipient survival in renal transplant recipients. It can be helpful in identifying patients at higher risk for inferior transplant outcome as a target population for potential intervention. PMID- 22036943 TI - Downregulation of the renal and hepatic hydrogen sulfide (H2S)-producing enzymes and capacity in chronic kidney disease. AB - BACKGROUND: Oxidative stress and inflammation are constant features and major mediators of progression and cardiovascular complications of chronic kidney disease (CKD). Hydrogen sulfide (H(2)S) is an endogenous signaling gas, which possesses potent anti-oxidant, anti-inflammatory, anti-hypertensive and other regulatory functions. H(2)S is produced by cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (MST). Plasma H(2)S is reduced in humans with hypertension, atherosclerosis and end stage renal disease (ESRD). Atherosclerosis, hypertension and ischemia/reperfusion-induced acute kidney injury are associated with and, in part, mediated by diminished tissue H(2)S in experimental animals. Expression of the H(2)S-producing enzymes is reduced in the circulating leukocytes of patients with ESRD. However, the effect of CKD on expression of H(2)S-producing enzymes in the diseased kidney and other tissues is unknown and was studied here. METHODS: Subgroups of rats were subjected to 5/6 nephrectomy or sham operation and observed for 6-12 weeks. Expression of H(2)S-producing enzymes and H(2)S producing capacity was measured in kidney, liver and brain tissues. RESULTS: The CKD group exhibited oxidative stress and significant reduction of plasma H(2)S concentration. This was associated with marked reduction of H(2)S-producing capacity of the kidney and liver, marked downregulation of CBS, CSE and MST in the kidney and of CBS and CSE expression in the liver. However, expression of H(2)S-producing enzymes in the brain was not significantly altered in CKD rats. CONCLUSIONS: CKD is associated with significant reduction in plasma H(2)S concentration, diminished remnant kidney and liver tissue H(2)S-producing capacity and downregulation of the H(2)S-producing enzymes. Given the potent anti oxidant, anti-inflammatory and cytoprotective properties of H(2)S, its deficiency may contribute to progression of CKD and the associated complications. PMID- 22036944 TI - Predictive value of circulating endothelial microparticles for cardiovascular mortality in end-stage renal failure: a pilot study. AB - BACKGROUND: Endothelial dysfunction in cardiovascular (CV) diseases is closely associated with increases in plasma level of shed membrane microparticles (MPs) of endothelial origin. As arterial damage is a major contributor to CV mortality, we examined whether or not increases in endothelial microparticles (EMPs) circulating levels could predict outcome in patients with end-stage renal disease (ESRD). METHODS: This prospective pilot study conducted in a community hospital (median follow-up: 50.5 months), included 81 stable haemodialysed ESRD patients (59 +/- 14 years; 63% male). Platelet-free plasma obtained 72 h after last dialysis was analysed by flow cytometry, and MPs cellular origin identified as endothelial (CD31+CD41-MPs; EMPs), platelets (CD31+CD41+MPs) or erythrocyte (CD235a+MPs). The main outcome measures were global and CV mortality (fatal myocardial infarction, stroke, acute pulmonary oedema and sudden cardiac death). RESULTS: Non-survivors (n = 24) were older (P < 0.001) and characterized by higher levels of EMPs (P < 0.01) and high-sensitivity C-reactive protein (P < 0.05) and lower diastolic blood pressure (P < 0.001). Kaplan-Meier analysis demonstrated significantly higher probability of all-cause (P < 0.001) and CV mortality (P < 0.0001) between the lower and upper EMPs tertiles. Multivariate Cox regression analysis demonstrated that baseline EMP levels independently predicted all-cause [hazard ratio (HR) = 21.7, 95% confidence interval (CI): 4.23 111.18 per log EMPs/MUL; P = 0.0002] and CV mortality (HR = 20.0, 95% CI: 3.86 103.5) per log EMPs/MUL; P < 0.0004) after adjustment for confounding factors. EMPs baseline level was a stronger predictor of poor outcome than classical risk factors. CONCLUSION: This study demonstrates that increased plasma levels of EMPs is a robust independent predictor of severe CV outcome in end-stage renal failure patients. PMID- 22036945 TI - High-salt diet increases glomerular ACE/ACE2 ratio leading to oxidative stress and kidney damage. AB - BACKGROUND: Angiotensin II (AngII) contributes to salt-driven kidney damage. In this study, we aimed at investigating whether and how the renal damage associated with a high-salt diet could result from changes in the ratio between angiotensin converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2). METHODS: Forty-eight rats randomly allocated to three different dietary contents of salt were studied for 4 weeks after undergoing a left uninephrectomy. We focussed on kidney functional, structural and molecular changes. At the same time, we studied kidney molecular changes in 20 weeks old Ace2-knockout mice (Ace2KO), with and without ACE inhibition. RESULTS: A high salt content diet significantly increased the glomerular ACE/ACE2 ratio. This was associated with increased oxidative stress. To assess whether these events were related, we measured renal oxidative stress in Ace2KO, and found that the absence of ACE2 promoted oxidative stress, which could be prevented by ACE inhibition. CONCLUSION: One of the mechanisms by which a high-salt diet leads to renal damage seems to be the modulation of the ACE/ACE2 ratio which in turn is critical for the cause of oxidative stress, through AngII. PMID- 22036946 TI - Workplace weight loss program: impact on quality of life. AB - OBJECTIVE: To determine the effectiveness of a 12-week workplace intervention program (WIP) focused on weight loss and reduction of cardiovascular risk factors on health-related quality of life (HRQOL) and the effect of delivery method on outcomes. METHODS: A retrospective analysis of data collected in a 12-week trial comparing in-person (IP) and Internet-based (IB) intervention to identify the impact on HRQOL by utilizing the Centers for Disease Control and Prevention HRQOL 14 questionnaire. RESULTS: Repeated-measure analysis of variance indicated no significant intervention effect for HRQOL by group assignment. Within subjects, significant main effect was noted for improvement in Summative Index of unhealthy days, sleeplessness, and vitality days at weeks 12 and 26. At week 26, significant main effect was found for improved mentally unhealthy and depression days. CONCLUSIONS: Improvement in HRQOL following a 12-week university-based WIP can occur independent of method of delivery (IP vs IB). PMID- 22036947 TI - Expression of type I interferon by splenic macrophages suppresses adaptive immunity during sepsis. AB - Early during Gram-negative sepsis, excessive release of pro-inflammatory cytokines can cause septic shock that is often followed by a state of immune paralysis characterized by the failure to mount adaptive immunity towards secondary microbial infections. Especially, the early mechanisms responsible for such immune hypo-responsiveness are unclear. Here, we show that TLR4 is the key immune sensing receptor to initiate paralysis of T-cell immunity after bacterial sepsis. Downstream of TLR4, signalling through TRIF but not MyD88 impaired the development of specific T-cell immunity against secondary infections. We identified type I interferon (IFN) released from splenic macrophages as the critical factor causing T-cell immune paralysis. Early during sepsis, type I IFN acted selectively on dendritic cells (DCs) by impairing antigen presentation and secretion of pro-inflammatory cytokines. Our results reveal a novel immune regulatory role for type I IFN in the initiation of septic immune paralysis, which is distinct from its well-known immune stimulatory effects. Moreover, we identify potential molecular targets for therapeutic intervention to overcome impairment of T-cell immunity after sepsis. PMID- 22036950 TI - Arterial waveform analysis in anesthesia and critical care. AB - PURPOSE OF REVIEW: In this review, we describe the basic principles of arterial waveform analysis (AWA) to assess cardiac output (CO) and cardiac preload. The validity of commercially based hemodynamic monitoring systems is discussed, together with their clinical applications and limitations. RECENT FINDINGS: Currently, three devices (the FloTrac system, PiCCO monitor, and LiDCO system) are available for measurement of AWA-based CO. In addition, dynamic preload parameters such as stroke volume variation (SVV) and pulse pressure variation (PPV) are determined, which may be useful to predict fluid responsiveness in mechanically ventilated patients. SUMMARY: AWA provides a less invasive and easy to-use alternative for CO measurement. The validity of AWA devices has been verified in a variety of patients and circumstances, but their performance is compromised in the presence of hemodynamic instability, cardiac arrhythmias, or other factors disturbing the arterial pressure waveform. The definitive role of dynamic preload parameters like SVV and PPV is a matter of research. Large trials in which the value of early goal-directed therapy using this technology is studied in relation to outcome are urgently needed. PMID- 22036949 TI - Coreceptor gene imprinting governs thymocyte lineage fate. AB - Immature thymocytes are bipotential cells that are signalled during positive selection to become either helper- or cytotoxic-lineage T cells. By tracking expression of lineage determining transcription factors during positive selection, we now report that the Cd8 coreceptor gene locus co-opts any coreceptor protein encoded within it to induce thymocytes to express the cytotoxic-lineage factor Runx3 and to adopt the cytotoxic-lineage fate, findings we refer to as 'coreceptor gene imprinting'. Specifically, encoding CD4 proteins in the endogenous Cd8 gene locus caused major histocompatibility complex class II specific thymocytes to express Runx3 during positive selection and to differentiate into CD4(+) cytotoxic-lineage T cells. Our findings further indicate that coreceptor gene imprinting derives from the dynamic regulation of specific cis Cd8 gene enhancer elements by positive selection signals in the thymus. Thus, for coreceptor-dependent thymocytes, lineage fate is determined by Cd4 and Cd8 coreceptor gene loci and not by the specificity of T-cell antigen receptor/coreceptor signalling. This study identifies coreceptor gene imprinting as a critical determinant of lineage fate determination in the thymus. PMID- 22036948 TI - Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function. AB - Mobilization of intracellular Ca(2+) stores regulates a multitude of cellular functions, but the role of intracellular Ca(2+) release via the ryanodine receptor (RyR) in the brain remains incompletely understood. We found that nitric oxide (NO) directly activates RyRs, which induce Ca(2+) release from intracellular stores of central neurons, and thereby promote prolonged Ca(2+) signalling in the brain. Reversible S-nitrosylation of type 1 RyR (RyR1) triggers this Ca(2+) release. NO-induced Ca(2+) release (NICR) is evoked by type 1 NO synthase-dependent NO production during neural firing, and is essential for cerebellar synaptic plasticity. NO production has also been implicated in pathological conditions including ischaemic brain injury, and our results suggest that NICR is involved in NO-induced neuronal cell death. These findings suggest that NICR via RyR1 plays a regulatory role in the physiological and pathophysiological functions of the brain. PMID- 22036951 TI - Technology, education, training and information systems. PMID- 22036952 TI - The gap-junction inhibitor carbenoxolone suppresses the differentiation of Th17 cells through inhibition of IL-23 expression in antigen presenting cells. AB - Carbenoxolone (CBX) is a widely used gap-junction inhibitor. We have previously shown that treatment with CBX significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE). However, the mechanism by which CBX delays the onset of EAE remains to be elucidated. Here, we show that CBX specifically inhibits the production of IL-23 by dendritic cells (DCs) and microglia in vitro. CBX treatment significantly reduced the population of Th17 cells in EAE mice. Furthermore, CBX downregulated the expression of IL-23 p19 via increased production of protein phosphatase 2A (PP2A). Thus, CBX may be an effective therapeutic strategy against Th17-mediated autoimmune diseases, such as multiple sclerosis. PMID- 22036953 TI - Cerebrospinal fluid levels of CXCL13 are elevated in neuromyelitis optica. AB - BACKGROUND: B cells are believed to play an important role in the pathogenesis of NMO. Chemokine (C-X-C motif) ligand 13 (CXCL13), the most potent B-cell chemoattractant, is a chemokine which is critical for secondary lymphoid tissue development and for B-cell migration. Concentration of CXCL13 in cerebral spinal fluid (CSF) is elevated in patients with multiple sclerosis (MS). However, whether levels of CSF CXCL13 are elevated in NMO patients still remain unknown. OBJECTIVE: To measure the CSF concentration of CXCL13 in NMO patients, and to determine its relationship with NMO disease activity. METHODS: CSF CXCL13 was measured by an enzyme-linked immunosorbent assay (ELISA) in NMO (n=22), MS (n=18) patients and controls (CTLs) (n=12). RESULTS: CSF CXCL13 levels in NMO were notable higher than MS (p=0.015) and CTLs (p<0.001), and were related to the NMO disease activity indicated by relapse rate and Expanded Disability Status Scale (EDSS) scores. NMO Patients with the higher relapse rates exhibited the higher CXCL13 concentrations in their CSF; and a trend of increased disease disability with increased CSF CXCL13 level was revealed. The CSF CXCL13 concentrations seemed to associate with CSF white blood cell counting, total protein concentration in NMO subgroup, thought did not quite reach statistical significance (WBC, p=0.473; TP, p=0.276). CONCLUSIONS: The concentration of CSF CXCL13 was elevated in NMO patients, and correlated with NMO activity. PMID- 22036954 TI - Immune cell NT-3 expression is associated with brain atrophy in multiple sclerosis patients. AB - While neurotrophins mediate cell survival and proliferation in the nervous system, they are also expressed within peripheral blood mononuclear cells (PBMCs) of the immunological system. In multiple sclerosis (MS) neurotrophins released from PBMCs might play a neuroprotective role, delaying neurodegeneration within central nervous system. We aimed for identifying the link between neurotrophins' PBMCs expression and brain atrophy markers in relapsing-remitting MS (RRMS) patients. We have found that neurotrophin-3 PBMCs concentration is strongly correlated with brain-parenchymal fraction and corpus callosum cross-sectional area, which are well-established brain atrophy measures. Thus, PBMC-derived neurotrophin-3 might exert a direct or indirect neuroprotective effect in MS. PMID- 22036955 TI - Informed consent process for patient participation in rare disease registries linked to biorepositories. PMID- 22036956 TI - [European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. European Association of Urology Guideline Group for urothelial cell carcinoma of the upper urinary tract]. AB - CONTEXT: The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice. OBJECTIVE: This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references. EVIDENCE SYNTHESIS: There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options. CONCLUSIONS: These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient's specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status. PMID- 22036957 TI - Impairments of auditory scene analysis in Alzheimer's disease. AB - Parsing of sound sources in the auditory environment or 'auditory scene analysis' is a computationally demanding cognitive operation that is likely to be vulnerable to the neurodegenerative process in Alzheimer's disease. However, little information is available concerning auditory scene analysis in Alzheimer's disease. Here we undertook a detailed neuropsychological and neuroanatomical characterization of auditory scene analysis in a cohort of 21 patients with clinically typical Alzheimer's disease versus age-matched healthy control subjects. We designed a novel auditory dual stream paradigm based on synthetic sound sequences to assess two key generic operations in auditory scene analysis (object segregation and grouping) in relation to simpler auditory perceptual, task and general neuropsychological factors. In order to assess neuroanatomical associations of performance on auditory scene analysis tasks, structural brain magnetic resonance imaging data from the patient cohort were analysed using voxel based morphometry. Compared with healthy controls, patients with Alzheimer's disease had impairments of auditory scene analysis, and segregation and grouping operations were comparably affected. Auditory scene analysis impairments in Alzheimer's disease were not wholly attributable to simple auditory perceptual or task factors; however, the between-group difference relative to healthy controls was attenuated after accounting for non-verbal (visuospatial) working memory capacity. These findings demonstrate that clinically typical Alzheimer's disease is associated with a generic deficit of auditory scene analysis. Neuroanatomical associations of auditory scene analysis performance were identified in posterior cortical areas including the posterior superior temporal lobes and posterior cingulate. This work suggests a basis for understanding a class of clinical symptoms in Alzheimer's disease and for delineating cognitive mechanisms that mediate auditory scene analysis both in health and in neurodegenerative disease. PMID- 22036958 TI - Patterns of spontaneous and head-shaking nystagmus in cerebellar infarction: imaging correlations. AB - Horizontal head-shaking may induce nystagmus in peripheral as well as central vestibular lesions. While the patterns and mechanism of head-shaking nystagmus are well established in peripheral vestibulopathy, they require further exploration in central vestibular disorders. To define the characteristics and mechanism of head-shaking nystagmus in central vestibulopathies, we investigated spontaneous nystagmus and head-shaking nystagmus in 72 patients with isolated cerebellar infarction. Spontaneous nystagmus was observed in 28 (39%) patients, and was mostly ipsilesional when observed in unilateral infarction (15/18, 83%). Head-shaking nystagmus developed in 37 (51%) patients, and the horizontal component of head-shaking nystagmus was uniformly ipsilesional when induced in patients with unilateral infarction. Perverted head-shaking nystagmus occurred in 23 (23/37, 62%) patients and was mostly downbeat (22/23, 96%). Lesion subtraction analyses revealed that damage to the uvula, nodulus and inferior tonsil was mostly responsible for generation of head-shaking nystagmus in patients with unilateral posterior inferior cerebellar artery infarction. Ipsilesional head shaking nystagmus in patients with unilateral cerebellar infarction may be explained by unilateral disruption of uvulonodular inhibition over the velocity storage. Perverted (downbeat) head-shaking nystagmus may be ascribed to impaired control over the spatial orientation of the angular vestibulo-ocular reflex due to uvulonodular lesions or a build-up of vertical vestibular asymmetry favouring upward bias due to lesions involving the inferior tonsil. PMID- 22036959 TI - The 'headache tree' via umbellulone and TRPA1 activates the trigeminovascular system. AB - The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt., is known as the 'headache tree' because the inhalation of its vapours can cause severe headache crises. However, the underlying mechanism of the headache precipitating properties of Umbellularia californica is unknown. The monoterpene ketone umbellulone, the major volatile constituent of the leaves of Umbellularia californica, has irritating properties, and is a reactive molecule that rapidly binds thiols. Thus, we hypothesized that umbellulone stimulates the transient receptor potential ankyrin 1 channel in a subset of peptidergic, nocioceptive neurons, activating the trigeminovascular system via this mechanism. Umbellulone, from uM to sub-mM concentrations, selectively stimulated transient receptor potential ankyrin 1-expressing HEK293 cells and rat trigeminal ganglion neurons, but not untransfected cells or neurons in the presence of the selective transient receptor potential ankyrin 1 antagonist, HC-030031. Umbellulone evoked a calcium dependent release of calcitonin gene-related peptide from rodent trigeminal nerve terminals in the dura mater. In wild-type mice, umbellulone elicited excitation of trigeminal neurons and released calcitonin gene-related peptide from sensory nerve terminals. These two responses were absent in transient receptor potential ankyrin 1 deficient mice. Umbellulone caused nocioceptive behaviour after stimulation of trigeminal nerve terminals in wild-type, but not transient receptor potential ankyrin 1 deficient mice. Intranasal application or intravenous injection of umbellulone increased rat meningeal blood flow in a dose dependent manner; a response selectively inhibited by systemic administration of transient receptor potential ankyrin 1 or calcitonin gene-related peptide receptor antagonists. These data indicate that umbellulone activates, through a transient receptor potential ankyrin 1-dependent mechanism, the trigeminovascular system, thereby causing nocioceptive responses and calcitonin gene-related peptide release. Pharmacokinetics of umbellulone, given by either intravenous or intranasal administration, suggest that transient receptor potential ankyrin 1 stimulation, which eventually results in meningeal vasodilatation, may be produced via two different pathways, depending on the dose. Transient receptor potential ankyrin 1 activation may either be caused directly by umbellulone, which diffuses from the nasal mucosa to perivascular nerve terminals in meningeal vessels, or by stimulation of trigeminal endings within the nasal mucosa and activation of reflex pathways. Transient receptor potential ankyrin 1 activation represents a plausible mechanism for Umbellularia californica-induced headache. Present data also strengthen the hypothesis that a series of agents, including chlorine, cigarette smoke, formaldehyde and others that are known to be headache triggers and recently identified as transient receptor potential ankyrin 1 agonists, utilize the activation of this channel on trigeminal nerves to produce head pain. PMID- 22036960 TI - The cerebellar cognitive profile. AB - The cerebellar role in non-motor functions is supported by the clinical finding that lesions confined to cerebellum produce the cerebellar cognitive affective syndrome. Nevertheless, there is no consensus regarding the overall cerebellar contribution to cognition. Among other reasons, this deficiency might be attributed to the small sample sizes and narrow breadths of existing studies on lesions in cerebellar patients, which have focused primarily on a single cognitive domain. The aim of this study was to examine the expression of cerebellar cognitive affective syndrome with regard to lesion topography in a large group of subjects with cerebellar damage. We retrospectively analysed charts from patients in the Ataxia Lab of Santa Lucia Foundation between 1997 and 2007. Of 223 charts, 156 were included in the study, focusing on the importance of the cerebellum in cognition and the relevance of lesion topography in defining the cognitive domains that have been affected. Vascular topography and the involvement of deep cerebellar nuclei were the chief factors that determined the cognitive profile. Of the various cognitive domains, the ability to sequence was the most adversely affected in nearly all subjects, supporting the hypothesis that sequencing is a basic cerebellar operation. PMID- 22036961 TI - Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options. AB - Complex I deficiency is the most frequent cause of oxidative phosphorylation disorders. The disease features a large diversity of clinical symptoms often leading to progressive encephalomyopathies with a fatal outcome. There is currently no cure, and although disease-causing mutations have been found in the genes encoding complex I subunits, half of the cases remain unexplained. However, in the past 5 years a new class of complex I disease genes has emerged with the finding of specific assembly factors. So far nine such genes have been described and it is believed that in the near future more will be found. In this review, we will address whether the functions of these chaperones point towards a general molecular mechanism of disease and whether this enables us to design a treatment for complex I deficiency. PMID- 22036962 TI - Stimulation of the human cortex and the experience of pain: Wilder Penfield's observations revisited. AB - Thanks to the seminal work of Wilder Graves Penfield (1891-1976) at the Montreal Neurological Institute, electrical stimulation is used worldwide to localize the epileptogenic cortex and to map the functionally eloquent areas in the context of epilepsy surgery or lesion resections. In the functional map of elementary and experiential responses he described through >20 years of careful exploration of the human cortex via stimulation of the cortical surface, Penfield did not identify any 'pain cortical area'. We reinvestigated this issue by analysing subjective and videotaped behavioural responses to 4160 cortical stimulations using intracerebral electrodes implanted in all cortical lobes that were carried out over 12 years during the presurgical evaluation of epilepsy in 164 consecutive patients. Pain responses were scarce (1.4%) and concentrated in the medial part of the parietal operculum and neighbouring posterior insula where pain thresholds showed a rostrocaudal decrement. This deep cortical region remained largely inaccessible to the intraoperative stimulation of the cortical surface carried out by Penfield after resection of the parietal operculum. It differs also from primary sensory areas described by Penfield et al. in the sense that, with our stimulation paradigm, pain represented only 10% of responses. Like Penfield et al., we obtained no pain response anywhere else in the cortex, including in regions consistently activated by pain in most functional imaging studies, i.e. the first somatosensory area, the lateral part of the secondary somatosensory area, anterior and mid-cingulate gyri (mid-cingulate cortex), anterior frontal, posterior parietal and supplementary motor areas. The medial parietal operculum and posterior insula are thus the only areas where electrical stimulation is able to trigger activation of the pain cortical network and thus the experience of somatic pain. PMID- 22036963 TI - Scope and application of therapeutic apheresis: Experience from a tertiary care hospital in North India. AB - BACKGROUND: We present here our experience with therapeutic apheresis (TA) performed for various indications, clinical response and complications in a tertiary care center over last 10 years. STUDY DESIGN AND METHODS: Present study is a retrospective analysis of 492 TA procedures performed for 125 patients from January 2000 to December 2009. For each patient: age, gender, weight, clinical indication, pre-procedure hematological profile and ionized calcium levels were recorded. For every procedure following parameters were analyzed: type of venous access (central/peripheral), volume of blood and plasma processed, amount of anticoagulant used, procedure duration, blood flow rate, type of replacement fluid given, response to therapy and adverse reactions. RESULTS: Of 492 TA procedures, 68.8% were performed for neurology, 20.8% hematology-oncology, 9.6% renal and 0.8% for rheumatology patients. Therapeutic plasma exchanges (n=464; 94.3%) and therapeutic cytapheresis (n=28; 6.7%) were performed in 113 and 12 patients, respectively. Majority of patients belonged to ASFA category I and II (n=124; 99.2%). The overall response rate was 84%, with encouraging response in TTP (100%), aHUS (81.8%) and in neurological disorders (88.4%). Adverse events were reported in 52.8% of patients in 14.83% of procedures. CONCLUSION: Our results of TPE in neurological disorders and in atypical hemolytic uremic syndrome are encouraging and it is a cost effective alternative to IvIg in neurological disorders. Currently, there is a need for establishment of an Indian apheresis registry to understand the scenario of TA across the country and in the expansion of appropriate and applicable indications for TA in our setting. PMID- 22036965 TI - Fragrance material review on 2,2-dimethyl-3-phenylpropanol. AB - A toxicologic and dermatologic review of 2,2-dimethyl-3-phenylpropanol when used as a fragrance ingredient is presented. 2,2-Dimethyl-3-phenylpropanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2,2-dimethyl-3-phenylpropanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, phototoxicity, and photoallergy data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036964 TI - Notch signaling proteins HES-1 and Hey-1 bind to insulin degrading enzyme (IDE) proximal promoter and repress its transcription and activity: implications for cellular Abeta metabolism. AB - Cerebral amyloid beta (Abeta) accumulation is pathogenically associated with sporadic Alzheimer's disease (SAD). BACE-1 is involved in Abeta generation while insulin-degrading enzyme (IDE) partakes in Abeta proteolytic clearance. Vulnerable regions in AD brains show increased BACE-1 protein levels and enzymatic activity while the opposite occurs with IDE. Another common feature in SAD brains is Notch1 overexpression. Here we demonstrate an increase in mRNA levels of Hey-1, a Notch target gene, and a decrease of IDE transcripts in the hippocampus of SAD brains as compared to controls. Transient transfection of Notch intracellular domain (NICD) in N2aSW cells, mouse neuroblastoma cells (N2a) stably expressing human amyloid precursor protein (APP) Swedish mutation, reduce IDE mRNA levels, promoting extracellular Abeta accumulation. Also, NICD, HES-1 and Hey-1 overexpression result in decreased IDE proximal promoter activity. This effect was mediated by 2 functional sites located at -379/-372 and -310-303 from the first translation start site in the -575/-19 (556 bp) fragment of IDE proximal promoter. By site-directed mutagenesis of the IDE promoter region we reverted the inhibitory effect mediated by NICD transfection suggesting that these sites are indeed responsible for the Notch-mediated inhibition of the IDE gene expression. Intracranial injection of the Notch ligand JAG-1 in Tg2576 mice, expressing the Swedish mutation in human APP, induced overexpression of HES-1 and Hey-1 and reduction of IDE mRNA levels, respectively. Our results support our theory that a Notch-dependent IDE transcriptional modulation may impact on Abeta metabolism providing a functional link between Notch signaling and the amyloidogenic pathway in SAD. PMID- 22036966 TI - Natural polyphenols may ameliorate damage induced by copper overload. AB - The effect of the simultaneous exposure to transition metals and natural antioxidants frequently present in food is a question that needs further investigation. We aimed to explore the possible use of the natural polyphenols caffeic acid (CA), resveratrol (RES) and curcumin (CUR) to prevent damages induced by copper-overload on cellular molecules in HepG2 and A-549 human cells in culture. Exposure to 100MUM/24h copper (Cu) caused extensive pro-oxidative damage evidenced by increased TBARS, protein carbonyls and nitrite productions in both cell types. Damage was aggravated by simultaneous incubation with 100MUM of CA or RES, and it was also reflected in a decrease on cellular viability explored by trypan blue dye exclusion test and LDH leakage. Co-incubation with CUR produced opposite effects demonstrating a protective action which restored the level of biomarkers and cellular viability almost to control values. Thus, while CA and RES might aggravate the oxidative/nitrative damage of Cu, CUR should be considered as a putative protective agent. These results could stimulate further research on the possible use of natural polyphenols as neutralizing substances against the transition metal over-exposure in specific populations such as professional agrochemical sprayers and women using Cu-intrauterine devices. PMID- 22036967 TI - Fragrance material review on beta,beta,3-trimethyl-benzenepropanol. AB - A toxicologic and dermatologic review of beta,beta,3-trimethyl-benzenepropanol when used as a fragrance ingredient is presented. beta,beta,3-Trimethyl benzenepropanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for beta,beta,3-trimethyl benzenepropanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, repeated dose, and genotoxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036968 TI - Fragrance material review on 2-p-tolylethanol. AB - A toxicologic and dermatologic review of 2-p-tolylethanol when used as a fragrance ingredient is presented. 2-p-tolylethanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group-C (R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all other branched chain saturated alcohols in fragrances. PMID- 22036969 TI - Fragrance material review on p-alpha,alpha-trimethylbenzyl alcohol. AB - A toxicologic and dermatologic review of p-alpha,alpha-trimethylbenzyl alcohol when used as a fragrance ingredient is presented. p-alpha,alpha-Trimethylbenzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a tertiary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for p-alpha,alpha trimethylbenzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitisation, toxicokinetics, and genotoxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036970 TI - Fragrance material review on 3-methyl-1-phenylbutan-2-ol. AB - A toxicologic and dermatologic review of 3-methyl-1-phenylbutan-2-ol when used as a fragrance ingredient is presented. 3-Methyl-1-phenylbutan-2-ol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 3-methyl-1-phenylbutan-2-ol were evaluated then summarized and includes physical properties and mucous membrane (eye) irritation data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all other branched chain saturated alcohols in fragrances. PMID- 22036971 TI - Fragrance material review on anisyl alcohol (o-m-p-). AB - A toxicologic and dermatologic review of anisyl alcohol (o-m-p-) when used as a fragrance ingredient is presented. Anisyl alcohol (o-m-p-) is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alkyl alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar(-)Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all other branched chain saturated alcohols in fragrances. PMID- 22036972 TI - Fragrance material review on phenylethyl alcohol. AB - A toxicologic and dermatologic review of phenylethyl alcohol when used as a fragrance ingredient is presented. Phenylethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C (R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for phenylethyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036973 TI - Fragrance material review on benzyl alcohol. AB - A toxicologic and dermatologic review of benzyl alcohol when used as a fragrance ingredient is presented. Benzyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for benzyl alcohol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, reproductive toxicity, genotoxicity, and carcinogenicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036974 TI - Protective effects of pine bark extract on developmental toxicity of cyclophosphamide in rats. AB - This study investigated the protective effects of pine bark extract (Pycnogenol(r), PYC) against cyclophosphamide (CP)-induced developmental toxicity in rats. A total of 44 mated females were randomly assigned to the following four experimental groups: (1) vehicle control, (2) CP, (3) CP&PYC, or (4) PYC. All dams were subjected to a Caesarean section on day 20 of gestation, and fetuses were examined for morphological abnormalities. Oxidative stress analysis was performed on maternal hepatic tissues. CP treatment caused decreased fetal and placental weights and increased embryonic resorptions and fetal malformations. In addition, an increased malondialdehyde (MDA) concentration and decreased reduced glutathione (GSH) content and catalase activity were observed in the hepatic tissues. On the contrary, PYC treatment during pregnancy significantly ameliorated the CP-induced embryo-fetal developmental toxicity in rats. Moreover, MDA and GSH concentrations and catalase activity in hepatic tissues were not affected when PYC was administered in conjunction with CP. These results suggest that repeated administration of PYC has beneficial effects against CP-induced embryo-fetal developmental toxicity in rats, and that the protective effects of PYC may be due to both inhibition of lipid peroxidation and increased antioxidant activity. PMID- 22036975 TI - Fragrance material review on o-tolylethanol. AB - A toxicologic and dermatologic review of safety data for o-tolylethanol when used as a fragrance ingredient is presented. o-Tolylethanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C (R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for o-tolylethanol were evaluated then summarized and includes physical properties, skin irritation, and skin sensitisation data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036976 TI - Fragrance material review on 2-methyl-4-phenylpentanol. AB - A toxicologic and dermatologic review of 2-methyl-4-phenylpentanol when used as a fragrance ingredient is presented. 2-Methyl-4-phenylpentanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C (R1)(R2)OH and generically the AAAs fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-methyl-4-phenylpentanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, repeated dose, and genotoxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036977 TI - Fragrance material review on alpha-isobutylphenethyl alcohol. AB - A toxicologic and dermatologic review of alpha-isobutylphenethyl alcohol when used as a fragrance ingredient is presented. alpha-Isobutylphenethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a secondary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for alpha-isobutylphenethyl alcohol were evaluated then summarized and includes physical properties, skin sensitization, and repeated dose data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036978 TI - Fragrance material review on 2-(3-methylphenyl) ethanol. AB - A toxicologic and dermatologic review of 2-(3-methylphenyl) ethanol when used as a fragrance ingredient is presented. 2-(3-Methylphenyl) ethanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all other branched chain saturated alcohols in fragrances. PMID- 22036979 TI - Caffeic acid attenuates 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced NF kappaB and COX-2 expression in mouse skin: abrogation of oxidative stress, inflammatory responses and proinflammatory cytokine production. AB - Polyphenols are the abundant micronutrient in our diet and attention has been given to them for the prevention of degenerative diseases. Since over production of ROS and proinflammatory cytokine are often act as the triggers for the promotion stage of carcinogenesis by transcriptional up-regulation of nuclear factor-kappaB (NF-kappaB) and cycloxygenage-2 (COX-2). We investigated the protective effects of caffeic acid (CA) on 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced oxidative and inflammatory responses, expression of NF-kappaB and COX-2 in mouse skin. Animals were given pre-treatment of CA at two different doses 10MUmol (D1) and 20MUmol (D2)/0.2ml of acetone 30min prior to each TPA (10nmol/0.2ml of acetone) application. Our results show that CA significantly inhibit the TPA induced lipid peroxidation (LPO), inflammatory responses, tumor necrosis factor alpha (TNF-alpha) release and also found to up regulate GSH content and the activity of different antioxidant enzymes. Further, CA was found to inhibit the TPA induced expression of NF-kappaB and COX-2. Thus, our results suggest that CA attenuates TPA induced tumor promotional triggers possibly by inhibition of oxidative and inflammatory responses thereby diminishing the expression of NF-kappaB and COX-2. PMID- 22036980 TI - Fragrance material review on 2-phenoxyethanol. AB - A toxicologic and dermatologic review of 2-phenoxyethanol when used as a fragrance ingredient is presented. 2-Phenoxyethanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C (R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-phenoxyethanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, mucous membrane (eye) irritation, skin sensitization, elicitation, phototoxicity, photoallergy, toxicokinetics, repeated dose, and reproductive toxicity data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036981 TI - A hierarchical Bayesian mixture model for repeated dietary records. AB - Many dietary consumption variables show strong positive skewness or large proportions of zeros. Attempts to normalize such data using transformations such as powers and logarithms can be unsuccessful: this results in poor estimates of their probability distributions, and hence of the proportions of the population whose consumption is beyond recommended limits. As an alternative to such transformations, the use of finite mixtures of standard distributions offers flexible modeling of data having skewed or multi-modal distributions, such as data on dietary consumption. In many dietary studies, individuals are asked to report their consumptions on several days. The use of finite-mixture models for such repeated data requires generalization to take account of the resulting hierarchical structure in the data. We first consider how finite mixture models might be extended to data with repeated records, and then apply a Bayesian version of one such extension to data on the consumption of retinol (Vitamin A) by British adults over 7 consecutive days. We also illustrate how factors such as sex and age may be included in the model. The mixture-model approach is found to provide better estimates than alternative methods of the probability distributions of daily consumptions and of maximum consumption over 7days. PMID- 22036982 TI - Fragrance material review on 2-methyl-4-phenyl-2-butanol. AB - A toxicologic and dermatologic review of 2-methyl-4-phenyl-2-butanol when used as a fragrance ingredient is presented. 2-methyl-4-phenyl-2-butanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a tertiary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for 2-methyl-4-phenyl-2-butanol were evaluated then summarized and includes physical properties, acute toxicity, skin irritation, and skin sensitization data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. assessment of aryl alkyl alcohols when used as fragrance ingredients. PMID- 22036983 TI - Fragrance material review on alpha,alpha,4-trimethylphenethyl alcohol. AB - A toxicologic and dermatologic review of alpha,alpha,4-trimethylphenethyl alcohol when used as a fragrance ingredient is presented. alpha,alpha,4 Trimethylphenethyl alcohol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a tertiary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C-(R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C-(R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. Available data for alpha,alpha,4 trimethylphenethyl alcohol were evaluated then summarized and includes physical properties, skin irritation, mucous membrane (eye) irritation, and skin sensitization data. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al. (2012) for an overall assessment of the safe use of this material and all Aryl Alkyl Alcohols in fragrances. PMID- 22036984 TI - Isolation and identification of alpha-proteobacteria from Culex pipiens (Diptera Culicidae) larvae. AB - A survey of drainage ditches in suburban areas of La Plata, Buenos Aires province, Argentina for pathogens of Culex pipiens larvae was conducted from 2003 to 2006. C. pipiens larvae of opaque, white color were found in several of those field collections. When the white larvae were dissected and observed by phase contrast microscopy in wet-mount preparations, the presence of bacteria, located in the hemocoel, was recorded. Laboratory experiments were performed to elucidate the pathway for transmission of this pathogen. Although approaches involving traditional culturing had failed to reveal the identity of the new microorganism present, molecular techniques to identify the pathogen in the studies reported here were successful. The partial sequence of the 16S-rRNA gene constitutes a powerful tool for the detection of new isolates from the hemocoele of C. pipiens larvae. These bacteria were characterized as belonging to the genus Novispirillum. In spite of the genus's wide distribution in different aquatic environments, information related to the parasitic relationship of Novispirillum spp. to aquatic insects is scarce, and this association has not been described in other mosquito species. This report constitutes the first documentation of Novispirillum spp. as a pathogen for mosquito larvae. PMID- 22036985 TI - Lack of detection of a putative retrovirus associated with haemic neoplasia in the soft shell clam Mya arenaria. AB - Haemic neoplasia (HN) is a leukemia-like disease that affects at least 20 species of marine bivalves including soft shell clam, Mya arenaria. Since the disease was discovered in 1969, the etiology remains unknown. A retroviral etiology has been suggested based on the detection of reverse transcriptase activity and electron microscopic observation of retroviral-like particles using negative staining. To date, however no virus isolate and no retroviral sequence from HN has been obtained. Moreover, transmission of the disease by cell-free filtrate from affected clams has not been reproduced. In the current study, we reinvestigated the association of HN with a putative retrovirus. Sucrose gradient centrifugation followed by assessment of reverse transcriptase activity, electrophoretic analysis of protein and RNA, and electron microscopic examinations of fractions corresponding to retroviral density were employed. Detection of retroviral pol sequences using degenerate RT-PCR approaches was also attempted. Our results showed visible bands at the expected density of retrovirus in HN-positive and HN negative clam tissues and both with reverse transcriptase activity. Electron microscopy, RNA analysis, protein analysis, and PCR systems targeting the pol gene of retroviruses did not however provide clear evidence supporting presence of a retrovirus. We point out that the retrovirus etiology of HN of Mya arenaria proposed some 25 years ago should be reconsidered in the absence of a virus isolate or virus sequences. PMID- 22036986 TI - Lessons from 54 years of pharmaceutical research. PMID- 22036987 TI - HPV16 is associated with younger age in women with cervical intraepithelial neoplasia grade 2 and 3. AB - OBJECTIVE: To evaluate if women with HPV16 positive CIN2 and CIN3 are diagnosed at a younger age. METHODS: We conducted a population-based cohort study including more than 40,000 women having a liquid based cervical cytology sample taken as part of routine screening. HPV analysis was performed using Hybrid Capture 2 and LiPAv2. The study population was linked to the Danish Pathology Data Bank to retrieve information on subsequent cervical histology. We included HR HPV positive CIN2/3 samples, comprising 173 CIN2 and 467 CIN3 lesions. Due to a high number of multiple concurrent HPV infections, the causative HPV type was assigned to a hierarchically group. RESULTS: In CIN3, the estimated proportion of lesions positive for HPV16 was 68.1% among women aged 20 years and decreased to 38.9% among women aged 50 years. A decrease in HPV16 positivity with increasing age was also observed in CIN2. In a multinomial logistic regression analysis, young age was strongly associated with HPV16 positivity in CIN3 lesions (OR=0.46 per 10 year increase in age, 95% CI: 0.32-0.65). The proportion of HPV16 and/or 18 positive lesions among women diagnosed with CIN2 and CIN3 below 30 years of age was 44% and 75%, respectively. CONCLUSIONS: HPV16 positivity was significantly associated with younger age at diagnosis of CIN3. In a population vaccinated against HPV16 and 18, we will experience a shift to older ages in cervical precancerous lesions. These findings may imply that cervical cancer screening programs could start at an older age in HPV vaccinated populations. PMID- 22036988 TI - Pulmonary delivery of elcatonin using surface-modified liposomes to improve systemic absorption: polyvinyl alcohol with a hydrophobic anchor and chitosan oligosaccharide as effective surface modifiers. AB - The aim of this study was to investigate the feasibility of surface-modified liposomes for pulmonary delivery of a peptide. Chitosan oligosaccharide (oligoCS) and polyvinyl alcohol with a hydrophobic anchor (PVA-R) were used as surface modifiers. The effect of liposomal surface modification on the behavior of the liposomes on pulmonary administration and potential toxicity were evaluated in vitro and in vivo. In an association study with A549 cells, PVA-R modification reduced interaction with A549 cells, whereas oligoCS modification electrostatically enhanced cellular interaction. The therapeutic efficacy of elcatonin (eCT) after pulmonary administration to rats was significantly enhanced and prolonged for 48 h after separate administration with oligoCS- or PVA-R modified liposomes. oligoCS-modified liposomes adhered to lung tissues and caused opening of tight junctions, which enhanced eCT absorption. On the other hand, PVA R-modified liposomes induced long-term retention of eCT in the lung fluid, leading to sustained absorption. Consequently, surface modification of liposomes with oligoCS or PVA-R has potential for effective peptide drug delivery through pulmonary administration. PMID- 22036989 TI - Effect of ultraviolet filters on skin superoxide dismutase activity in hairless mice after a single dose of ultraviolet radiation. AB - Organic sunscreens may decrease their protective capability and also behave as photo-oxidants upon ultraviolet radiation (UVR) exposure. The present study investigated the effect of a cream gel formulation containing the UV filters benzophenone-3, octyl methoxycinnamate, and octyl salicylate on skin superoxide dismutase (SOD) after a single dose of UVR (2.87 J/cm(2)). The retention of these UV filters was first evaluated in vivo using hairless mice to guarantee the presence of the filters in the skin layers at the moment of irradiation. The in vivo effect of the UV filters on skin SOD was then assayed spectrophotometrically via the reduction of cytochrome c. The cream gel formulation promoted the penetration of the three UV filters into the epidermis and the dermis at one hour post-application. A significant decrease in SOD activity was observed in irradiated animals treated with sunscreen formulation. However, no effect on SOD activity in skin was observed by the isolated presence of the sunscreens, the formulation components, or the exposure to UVR. The sunscreens may have formed degradation products under UVR that may have either inhibited the enzyme or generated reactive species in the skin. PMID- 22036990 TI - Dissolution of a poorly water-soluble drug dry coated with magnesium and sodium stearate. AB - The purpose of this research was to investigate the influence of dry coating micronized cohesive powders of a poorly water-soluble drug, indomethacin with force control agents, on its dissolution performance. A dry mechanical fusion method (mechanofusion) was used to coat indomethacin powders with magnesium stearate (0.25%,1%,5%) and sodium stearate (5%). After mechanofusion, significantly increased bulk and tapped densities and decreased intrinsic cohesion were observed for all samples. X-ray photoelectron spectroscopy analysis confirmed that a thicker magnesium stearate surface coating was achieved with increasing concentrations of the material. Dissolution was studied using the USP paddle method in buffer pH 5.0; several modelling approaches were used to explore the dissolution mechanisms. Whilst the bi-exponential equation represented dissolution of mechanofused indomethacin powders occurring from dispersed and agglomerated particles, it provided unrealistic parameter estimates for the two coating materials of contrasting properties. Initial increases in indomethacin dissolution were dependent on the concentration of magnesium stearate mechanofused onto the drug powders. The dissolution enhancing effect of indomethacin powders mechanofused with 5% sodium stearate was attributed to its surfactant properties that increased dispersion of indomethacin agglomerates. Initial drug release from the coated powders was described by a matrix-diffusion system according to the Higuchi model. PMID- 22036991 TI - Benzothiazole-containing hydroxamic acids as histone deacetylase inhibitors and antitumor agents. AB - Data from clinical studies indicate that inhibitors of Class I and Class II histone deacetylase (HDAC) enzymes show great promise for the treatment of cancer. Zolinza (SAHA, Zolinza) was recently approved by the FDA for the treatment of the cutaneous manifestations of cutaneous T-cell lymphoma. As a part of our ongoing effort to identify novel small molecules to target these important enzymes, we have prepared two series of benzothiazole-containing analogues of SAHA. It was found that several compounds with 6C-bridge linking benzothiazole moiety and hydroxamic functional groups showed good inhibition against HDAC3 and 4 at as low as 1 MUg/ml and exhibited potent cytotoxicity against five cancer cell lines with average IC(50) values of as low as 0.81 MUg/ml, almost equipotent to SAHA. PMID- 22036992 TI - Diabetic nephropathy-related active cyclic peptides from the roots of Brachystemma calycinum. AB - Three new cyclic peptides, namely duanbanhuains A-C (1-3), were isolated from the roots of Brachystemma calycinum which is a traditional medicine used to treat rheumatic diseases. Their structures were identified by means of a suite of MS and NMR experiments. These compounds were purposely evaluated for their inhibitory effects on the release of MCP-1, IL-6, collagen IV and reactive oxygen species (ROS) against high-glucose-stimulated mesangial cells. The results showed that compounds 1 and 2 exhibited potent inhibition on the production of IL-6, collagen IV and ROS at the concentration of 10 MUM. PMID- 22036993 TI - Management of the stiff shoulder. A prospective multicenter comparative study of the six main techniques in use: 235 cases. AB - INTRODUCTION: Stiffness in the shoulder is a frequent symptom associated with a number of clinical entities whose management remains inadequately defined. PATIENTS AND METHODS: This prospective study of 235 cases of stiffness in the shoulder compared six therapeutic techniques with a mean follow-up of 13 months (range, 3-28 months) (T1: 58 cases, conventional rehabilitation under the pain threshold, T2: 59 cases, self-rehabilitation over the pain threshold, T3: 31 cases, T2 + supervision, T4: 11 cases, T1 + capsular distension, T5: 31 cases, T1 + locoregional anesthesia, T6: 45 cases, T1 + T5 + capsulotomy). The therapeutic power of each technique and its impact on the result were assessed at each self rehabilitation and rehabilitation session during the first 6 weeks and then at 3 months, 6 months, and at the final revision depending on subjective criteria (pain, discomfort, and morale) and objective criteria (Constant score, goniometric measurements). RESULTS: Conventional rehabilitation (T1) is less effective than self-rehabilitation over the pain threshold (T2 & T3) during the first 6 weeks (P<0.05). Self-rehabilitation stagnates between the 6th and 12th week except when it is supervised by a therapist (T3). Anesthesia (T4) and capsular distension (T5) do not lead to significantly different progression beyond 6 months. Capsulotomy does not demonstrate greater therapeutic power but its failure rate (persisting stiffness at 1 year) is 0% versus 14-17% for the other techniques (P<0.05). DISCUSSION: The techniques are complementary and therapeutic success stems from an algorithm adapted to the individual patient with, over the first 3 months, successive self-rehabilitation and conventional rehabilitation, possibly completed by capsular distension or anesthesia between the 3rd and 6th months. In case of failure at 6 months, endoscopic capsulotomy can be proposed. Therapeutic patient education and active participation are the key to treatment success or failure. PMID- 22036994 TI - Pain management in the rehabilitation of stiff shoulder: prospective multicenter comparative study of 193 cases. AB - INTRODUCTION: The present study investigated the impact of respecting pain threshold on clinical recovery in stiff shoulder. PATIENTS AND METHODS: A prospective multicenter comparative study followed up 193 cases of shoulder stiffness for a mean 12-month period (range, 8-31 months) after four different treatment protocols: (1) conventional sub-pain-threshold rehabilitation (58 cases); (2) self-rehabilitation exceeding the pain threshold (59 cases); (3) supervised suprathreshold rehabilitation (31 cases); and (4) capsulotomy with sub threshold rehabilitation (45 cases). Follow-up was daily for the first 6 weeks then weekly for the next 6; each session included assessment of the painfulness, feasibility and duration of each rehabilitation and self-rehabilitation exercise and of pain status, disability and psychological status. The surgeon followed patients up at 6 weeks, 3 months, 6 months, 1 year and at last follow-up. RESULTS: Sub-threshold rehabilitation provided progressive results, limited in time (P<0.05). Suprathreshold self-rehabilitation provided reduced pain (P<0.05) as of the first days, with nocturnal pain ceasing after 7 days' rehabilitation in 43% of cases. Supervision of self-rehabilitation exercises optimized the clinical result (P<0.05). Capsulotomy did not influence pain evolution over the first 8 weeks, but then improved it. Failure (at 1 year, 14-17%; last follow-up, 3.5%) correlated directly with the number of exercises performed by the patient (P<0.05). DISCUSSION: The dogma of respecting the pain threshold is dated: pain inflicted on a passive patient impairs clinical evolution, but pain managed by an informed active patient under experienced supervision provides rapid recovery of function and pain-free status. PMID- 22036996 TI - FMRI using balanced steady-state free precession (SSFP). AB - Steady-state free precession (SSFP) is a highly-efficient MRI pulse sequence that has been a fairly recent arrival in the functional MRI realm. Several methods for using balanced SSFP to detect the BOLD signal have been proposed to date and will be discussed in this review. After a brief introduction to the general properties of SSFP, this review describes the quite different approaches of transition-band and pass-band SSFP in terms of functional contrast mechanism. It then discusses the potential advantages of these techniques, followed by their challenges and shortcomings. Finally, it gives an overview of some applications considered to date and the author's perspective on where these techniques are headed. In the spirit of this special issue, the author also includes some of the personal history underlying her own explorations in this area. PMID- 22036995 TI - Spiral imaging in fMRI. AB - T2*-weighted Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) requires efficient acquisition methods in order to fully sample the brain in a several second time period. The most widely used approach is Echo Planar Imaging (EPI), which utilizes a Cartesian trajectory to cover k-space. This trajectory is subject to ghosts from off-resonance and gradient imperfections and is intrinsically sensitive to cardiac-induced pulsatile motion from substantial first- and higher order moments of the gradient waveform near the k-space origin. In addition, only the readout direction gradient contributes significant energy to the trajectory. By contrast, the spiral method samples k space with an Archimedean or similar trajectory that begins at the k-space center and spirals to the edge (spiral-out), or its reverse, ending at the origin (spiral-in). Spiral methods have reduced sensitivity to motion, shorter readout times, improved signal recovery in most frontal and parietal brain regions, and exhibit blurring artifacts instead of ghosts or geometric distortion. Methods combining spiral-in and spiral-out trajectories have further advantages in terms of diminished susceptibility-induced signal dropout and increased BOLD signal. In measurements of temporal signal to noise ratio measured in 8 subjects, spiral in/out exhibited significant increases over EPI in voxel volumes recovered in frontal and whole brain regions (18% and 10%, respectively). PMID- 22036997 TI - High resolution MR anatomy of the subthalamic nucleus: imaging at 9.4 T with histological validation. AB - Using conventional MRI the subthalamic nucleus (STN) is not clearly defined. Our objective was to define the anatomy of the STN using 9.4 T MRI of post mortem tissue with histological validation. Spin-echo (SE) and 3D gradient-echo (GE) images were obtained at 9.4 T in 8 post mortem tissue blocks and compared directly with corresponding histological slides prepared with Luxol Fast Blue/Cresyl Violet (LFB/CV) in 4 cases and Perl stain in 3. The variability of the STN anatomy was studied using internal reference points. The anatomy of the STN and surrounding structures was demonstrated in all three anatomical planes using 9.4 T MR images in concordance with LFB/CV stained histological sections. Signal hypointensity was seen in 6/8 cases in the anterior and medial STN that corresponded with regions of more intense Perl staining. There was significant variability in the volume, shape and location of the borders of the STN. Using 9.4 T MRI, the internal signal characteristics and borders of the STN are clearly defined and significant anatomical variability is apparent. Direct visualisation of the STN is possible using high field MRI and this is particularly relevant, given its anatomical variability, for planning deep brain stimulation. PMID- 22036998 TI - Towards source volume estimation of interictal spikes in focal epilepsy using magnetoencephalography. AB - Interictal spikes are a hallmark of cortical epileptogenicity; their spatial distribution in the cortex defines the so-called 'irritative' zone or spiking volume (SV). Delineating the SV precisely is a challenge during the presurgical evaluation of patients with epilepsy. Magnetoencephalography (MEG) recordings enable determination of the brain sources of epileptic spikes using source localization procedures. Most previous clinical MEG studies have relied on dipole modeling of epileptic spikes, which does not permit a volumetric estimation of the spiking cortex. In the present study, we propose a new source modeling procedure, Volumetric Imaging of Epileptic Spikes (VIES). In VIES, the SV is identified as the 3D region where sources of the high frequency activities (>20 Hz) associated with epileptic spikes are distributed. We localized these sources using a beamforming approach (DICS, Dynamic Imaging of Coherent Neural Sources). To determine the optimal parameters and accuracy of the method, we compared the SV obtained by VIES with the SV defined by the invasive gold standard, intracranial stereotactic EEG recordings (SEEG), in 21 patients with focal epilepsy. Using rigorous validation criteria based on the exact anatomical location of SEEG contacts, we found that the overall sensitivity of VIES for detecting spiking SEEG contacts was 76% and its specificity for correctly identifying non-spiking SEEG contacts was 67%, indicating a good agreement between VIES and SEEG. Moreover, we found that classical dipole clustering was not informative in 9/21 patients, while VIES enable to delineate the SV in all patients. For the 12 patients having a SV delineated both with VIES and dipole clustering, VIES method had higher sensitivity and lower specificity. This proof of-concept study shows that VIES is a promising approach to non-invasive estimation of the SV in focal epilepsy. PMID- 22036999 TI - Quantification of the cortical contribution to the NIRS signal over the motor cortex using concurrent NIRS-fMRI measurements. AB - Near-Infrared Spectroscopy (NIRS) measures the functional hemodynamic response occurring at the surface of the cortex. Large pial veins are located above the surface of the cerebral cortex. Following activation, these veins exhibit oxygenation changes but their volume likely stays constant. The back-reflection geometry of the NIRS measurement renders the signal very sensitive to these superficial pial veins. As such, the measured NIRS signal contains contributions from both the cortical region as well as the pial vasculature. In this work, the cortical contribution to the NIRS signal was investigated using (1) Monte Carlo simulations over a realistic geometry constructed from anatomical and vascular MRI and (2) multimodal NIRS-BOLD recordings during motor stimulation. A good agreement was found between the simulations and the modeling analysis of in vivo measurements. Our results suggest that the cortical contribution to the deoxyhemoglobin signal change (DeltaHbR) is equal to 16-22% of the cortical contribution to the total hemoglobin signal change (DeltaHbT). Similarly, the cortical contribution of the oxyhemoglobin signal change (DeltaHbO) is equal to 73-79% of the cortical contribution to the DeltaHbT signal. These results suggest that DeltaHbT is far less sensitive to pial vein contamination and therefore, it is likely that the DeltaHbT signal provides better spatial specificity and should be used instead of DeltaHbO or DeltaHbR to map cerebral activity with NIRS. While different stimuli will result in different pial vein contributions, our finger tapping results do reveal the importance of considering the pial contribution. PMID- 22037000 TI - Processing of unattended facial emotions: a visual mismatch negativity study. AB - Facial emotions express our internal states and are fundamental in social interactions. Here we explore whether the repetition of unattended facial emotions builds up a predictive representation of frequently encountered emotions in the visual system. Participants (n=24) were presented peripherally with facial stimuli expressing emotions while they performed a visual detection task presented in the center of the visual field. Facial stimuli consisted of four faces of different identity, but expressed the same emotion (happy or fearful). Facial stimuli were presented in blocks of oddball sequence (standard emotion: p=0.9, deviant emotion: p=0.1). Event-related potentials (ERPs) to the same emotions were compared when the emotions were deviant and standard, respectively. We found visual mismatch negativity (vMMN) responses to unattended deviant emotions in the 170-360 ms post-stimulus range over bilateral occipito-temporal sites. Our results demonstrate that information about the emotional content of unattended faces presented at the periphery of the visual field is rapidly processed and stored in a predictive memory representation by the visual system. We also found evidence that differential processing of deviant fearful faces starts already at 70-120 ms after stimulus onset. This finding shows a 'negativity bias' under unattended conditions. Differential processing of fearful deviants were more pronounced in the right hemisphere in the 195-275 ms and 360 390 ms intervals, whereas processing of happy deviants evoked larger differential response in the left hemisphere in the 360-390 ms range, indicating differential hemispheric specialization for automatic processing of positive and negative affect. PMID- 22037001 TI - Early electrophysiological indices of illusory contour processing within the lateral occipital complex are virtually impervious to manipulations of illusion strength. AB - The visual system can automatically interpolate or "fill-in" the boundaries of objects when inputs are fragmented or incomplete. A canonical class of visual stimuli known as illusory-contour (IC) stimuli has been extensively used to study this contour interpolation process. Visual evoked potential (VEP) studies have identified a neural signature of these boundary completion processes, the so called IC-effect, which typically onsets at 90-110 ms and is generated within the lateral occipital complex (LOC). Here we set out to determine the delimiting factors of automatic boundary completion with the use of illusory contour stimuli and high-density scalp recordings of brain activity. Retinal eccentricity, ratio of real to illusory contours (i.e. support ratio), and inducer diameter were each varied parametrically, and any resulting effects on the amplitude and latency of the IC-effect were examined. Somewhat surprisingly, the amplitude of the IC effect was found to be impervious to all changes in these stimulus parameters, manipulations that are known to impact perceived illusion strength. Thus, this automatic stage of object processing appears to be a binary process in which, so long as minimal conditions are met, contours are automatically completed. At the same time, the latency of the IC-effect was found to vary inversely with support ratio, likely reflecting the additional time necessary to interpolate across the relatively longer induced boundaries of the implied object. These data are interpreted in the context of a two stage object-recognition model that parses processing into an early automatic perceptual stage that is followed by a more effortful conceptual processing stage. PMID- 22037002 TI - The development of event-related fMRI designs. AB - The diversity of experimental designs that can be used with functional magnetic resonance imaging (fMRI) has played a key role in its widespread application to studies of human cognition. This flexibility is possible because the fMRI response to external stimuli is remarkably well approximated as the response of a linear time variant system. The experimental demonstration of this property provided the foundation for the development of event-related designs, in which the fMRI response is modeled as the linear summation of the hemodynamic response to discrete events. Building upon prior work from the fields of engineering, neuroscience, and statistics, researchers in the field have created a rich collection of event-related designs and developed a rigorous theoretical framework for characterizing and optimizing the performance of designs. Ongoing challenges include the optimization of designs in the presence of experimental constraints and the development of more time-efficient optimization algorithms. PMID- 22037003 TI - Future therapeutics for osteoarthritis. AB - Osteoarthritis (OA) is a disease of the joints that affects several million individuals worldwide. This disease, which involves mainly the diarthrodial joints, is chronic and develops slowly over decades, making it very difficult to precisely identify the different etiological and risk factors that influence its onset. At present, most therapies for OA are symptomatic. This review will focus on new OA therapeutics in development that are directed toward pain relief as well as others with the potential to reduce or stop the progression of the disease (DMOADs). This article is part of a Special Issue entitled "Osteoarthritis". PMID- 22037004 TI - Yellow-bellied marmots (Marmota flaviventris) preserve bone strength and microstructure during hibernation. AB - Reduced skeletal loading typically results in decreased bone strength and increased fracture risk for humans and many other animals. Previous studies have shown bears are able to prevent bone loss during the disuse that occurs during hibernation. Studies with smaller hibernators, which arouse intermittently during hibernation, show that they may lose bone at the microstructural level. These small hibernators, like bats and squirrels, do not utilize intracortical remodeling. However, slightly larger mammals like marmots do. In this study we examined the effects of hibernation on bone structural, mineral, and mechanical properties in yellow-bellied marmots (Marmota flaviventris). This was done by comparing cortical bone properties in femurs and trabecular bone properties in tibias from marmots killed before hibernation (fall) and after hibernation (spring). Age data were not available for this study; however, based on femur length the post-hibernation marmots were larger than the pre-hibernation marmots. Thus, cross-sectional properties were normalized by allometric functions of bone length for comparisons between pre- and post-hibernation. Cortical thickness and normalized cortical area were higher in post-hibernation samples; no other normalized cross-sectional properties were different. No cortical bone microstructural loss was evident in osteocyte lacunar measurements, intracortical porosity, or intracortical remodeling cavity density. Osteocyte lacunar area, porosity, and density were surprisingly lower in post-hibernation samples. Trabecular bone volume fraction was not different between pre- and post hibernation. Measures of both trabecular and cortical bone mineral content were higher in post-hibernation samples. Three-point bending failure load, failure energy, elastic energy, ultimate stress, and yield stress were all higher in post hibernation samples. These results support the idea that, like bears, marmots are able to prevent disuse osteoporosis during hibernation, thus preventing increased fracture risk and promoting survival of the extreme environmental conditions that occur in hibernation. PMID- 22037005 TI - Crystal structure of the VapBC toxin-antitoxin complex from Shigella flexneri reveals a hetero-octameric DNA-binding assembly. AB - Toxin-antitoxin (TA) loci are common in archaea and prokaryotes and allow cells to rapidly adapt to changing environmental conditions through release of active regulators of metabolism. Many toxins are endonucleases that target cellular mRNA and tRNAs, while the antitoxins tightly wrap around the toxins to inhibit them under normal circumstances. The antitoxins also bind to operators in the promoter regions of the cognate TA operon and thereby regulate transcription. For enteric vapBC TA loci, the VapC toxins specifically cleave tRNA(fMet) and thus down regulate protein synthesis. Here, we describe the crystal structure of the intact Shigella flexneri VapBC TA complex, determined to 2.7 A resolution. Both in solution and in the crystal structure, four molecules of each protein combine to form a large and globular hetero-octameric assembly with SpoVT/AbrB-type DNA binding domains at each end and a total molecular mass of about 100 kDa. The structure gives new insights into the inhibition of VapC toxins by VapB and provides the molecular basis for understanding transcriptional regulation through VapB dimerization. PMID- 22037006 TI - Emotion regulation predicts pain and functioning in children with juvenile idiopathic arthritis: an electronic diary study. AB - OBJECTIVES: This study utilized e-diaries to evaluate whether components of emotion regulation predict daily pain and function in children with juvenile idiopathic arthritis (JIA). METHODS: 43 children ages 8-17 years and their caregivers provided baseline reports of child emotion regulation. Children then completed thrice daily e-diary assessments of emotion, pain, and activity involvement for 28 days. E-diary ratings of negative and positive emotions were used to calculate emotion variability and to infer adaptive emotion modulation following periods of high or low emotion intensity. Hierarchical linear models were used to evaluate how emotion regulation related to pain and function. RESULTS: The attenuation of negative emotion following a period of high negative emotion predicted reduced pain; greater variability of negative emotion predicted higher pain and increased activity limitation. Indices of positive emotion regulation also significantly predicted pain. CONCLUSIONS: Components of emotion regulation as captured by e-diaries predict important health outcomes in children with JIA. PMID- 22037007 TI - Venous thromboembolism prophylaxis in palliative care patients. PMID- 22037008 TI - Moderation of distress-induced eating by emotional eating scores. AB - Earlier studies assessing the possible moderator effect of self-reported emotional eating on the relation between stress and actual food intake have obtained mixed results. The null findings in some of these studies might be attributed to misclassification of participants due to the use of the median splits and/or insufficient participants with extreme scores. The objective of the two current studies was to test whether it is possible to predict distress induced eating with a self-report emotional eating scale by using extreme scorers. In study 1 (n=45) we used a between-subjects design and emotional eating was assessed after food intake during a negative or a neutral mood (induced by a movie). In study 2 (n=47) we used a within-subjects design and emotional eating was assessed well before food intake, which occurred after a control or stress task (Trier Social Stress Task). The main outcome measure was actual food intake. In both studies self-reported emotional eating significantly moderated the relation between distress and food intake. As expected, low emotional eaters ate less during the sad movie or after stress than during the neutral movie or after the control task, whereas high emotional eaters ate more. No such moderator effect was found for emotional eating in the entire sample (n=124) of study 1 using the median-split procedure or the full range of emotional eating scores. We conclude that it is possible to predict distress-induced food intake using self reports of emotional eating provided that the participants have sufficiently extreme emotional eating scores. PMID- 22037009 TI - A proteasome-dependent, TAP-independent pathway for cross-presentation of phagocytosed antigen. AB - Major histocompatibility complex (MHC) class I cross-presentation is thought to involve two pathways, one of which depends on both the TAP transporters and the proteasome and the other on neither. We found that preincubation of TAP-deficient dendritic cells at low temperature increases the density of MHC class I at the surface and fully restores cross-presentation of phagocytosed antigen, but not of soluble antigen internalized through receptors. Restoration of cross-presentation by TAP-deficient cells requires antigen degradation by the proteasome. Thus, TAP might mainly be required for recycling cell surface class I molecules during cross-presentation of phagocytosed antigens. Furthermore, phagosomes-but not endosomes-seem to have a TAP-independent mechanism to import peptides generated by cytosolic proteasome complexes. PMID- 22037010 TI - Regulation of muscle protein synthesis in humans. AB - PURPOSE OF REVIEW: Investigations into the regulation of muscle protein synthesis (MPS) are a cornerstone of understanding the control of muscle mass. Rates of MPS are finely tuned according to levels of activity, nutrient availability and health status. For instance, rates of MPS are positively regulated by exercise and nutrition, and negatively regulated by inactivity (e.g. disuse), ageing (i.e. sarcopenia) and in muscle-wasting related diseases (e.g. cancer). RECENT FINDINGS: Skeletal muscles display a high degree of intrinsic regulation. Increases in MPS after exercise occur independently of the systemic milieu for example growth hormone/testosterone concentrations. In the absence of exercise, increases in MPS after feeding are of finite duration despite enduring precursor availability; that is muscles can sense they are 'full'. Intriguingly, exercise delays this 'muscle-full' response to allow for building and repair. In contrast, muscle-wasting conditions exhibit a premature 'muscle-full' response to nutrition and exercise (i.e. anabolic resistance), which may cause atrophy. Observations of 'dissociations' between MPS and anabolic signalling pathways have cast doubt on how much we understand of the molecular regulation of human MPS. SUMMARY: Anabolic and anticatabolic interventions in health and disease should be aimed at manipulating the 'muscle-full' set point to maximize muscle maintenance/hypertrophy. PMID- 22037011 TI - Arginases and arginine deficiency syndromes. AB - PURPOSE OF REVIEW: Many physiologic and pathophysiologic processes are modulated by arginine availability, which can be regulated by arginase. An understanding of the conditions that result in elevated arginase activity as well as the consequences of arginine deficiency is essential for design of effective nutritional support for disease. This review will emphasize recent findings regarding effects of plasma arginase and arginine deficiencies in disease. RECENT FINDINGS: Elevations in plasma arginase, derived primarily from hemolysis of red blood cells or liver damage, that are associated with arginine deficiency have been identified in an increasing number of diseases and conditions. Arginine insufficiency not only can activate a stress kinase pathway that impairs function of T lymphocytes but it also can inhibit the mitogen-activated protein kinase signaling pathway required for macrophage production of cytokines in response to bacterial endotoxin/lipopolysaccharide. SUMMARY: There are at least two broad categories of arginine deficiency syndromes, involving either T-cell dysfunction or endothelial dysfunction, depending on the disease context in which arginine deficiency occurs. There is limited information regarding the safety and efficacy of supplementation with arginine or its precursor citrulline in ameliorating arginine deficiency in specific diseases, indicating the need for further studies. PMID- 22037012 TI - Rethinking dietary cholesterol. AB - PURPOSE OF REVIEW: The perceived notion that dietary cholesterol is associated with increased risk for coronary heart disease (CHD) has led to dietary recommendations of no more than 300 mg/day for healthy populations in the USA. This study will review the recent evidence that challenges the current dietary restrictions regarding cholesterol while it presents some beneficial effects of eggs (an icon for dietary cholesterol) in healthy individuals. RECENT FINDINGS: The European countries, Australia, Canada, New Zealand, Korea and India among others do not have an upper limit for cholesterol intake in their dietary guidelines. Further, existing epidemiological data have clearly demonstrated that dietary cholesterol is not correlated with increased risk for CHD. Although numerous clinical studies have shown that dietary cholesterol challenges may increase plasma LDL cholesterol in certain individuals, who are more sensitive to dietary cholesterol (about one-quarter of the population), HDL cholesterol also rises resulting in the maintenance of the LDL/HDL cholesterol ratio, a key marker of CHD risk. SUMMARY: The lines of evidence coming from current epidemiological studies and from clinical interventions utilizing different types of cholesterol challenges support the notion that the recommendations limiting dietary cholesterol should be reconsidered. PMID- 22037013 TI - Leucine as a pharmaconutrient in health and disease. AB - PURPOSE OF REVIEW: Amino acids do not merely represent precursors for de-novo protein synthesis, but also function as nutritional signals regulating various metabolic processes. In fact, ample evidence has been generated to show that various tissues respond to changes in amino acid availability via signal transduction pathways that are also regulated by hormones such as insulin, glucagon, and insulin-like growth factor 1. RECENT FINDINGS: Amino acids, and leucine in particular, can act as strong insulin secretagogues when administered in combination with carbohydrate. Leucine administration can be applied effectively to improve postprandial glycemic control. Furthermore, amino acids have been shown to stimulate mRNA translation, thereby increasing muscle protein synthesis and stimulating net protein accretion in an insulin-independent manner. These anabolic properties of amino acids have been mainly attributed to the essential amino acids, and leucine in particular. In accordance, the recent in vivo human studies show that leucine ingestion can augment the blunted muscle protein synthetic response to protein or amino acid ingestion in elderly men. SUMMARY: Leucine has been proposed as a promising pharmaconutrient in the prevention and treatment of sarcopenia and/or type 2 diabetes. Though there are numerous applications for the proposed benefits of leucine in health and disease, the recent long-term nutritional intervention studies do not confirm the clinical efficacy of leucine as a pharmaconutrient. PMID- 22037014 TI - Mini nutritional assessment. AB - PURPOSE OF REVIEW: To summarize recent evidences and advances on the implementation and the use of the Mini Nutritional Assessment (MNA). RECENT FINDINGS: Despite being introduced and validated for clinical use about 20 years ago, the MNA has recently received new attention in order to more widely disseminate among healthcare professionals the practice of a systematic nutritional screening and assessment of the old patient. Particularly, the structure has been implemented to face the difficulties in having the patients contributing to the assessment and to reduce further the time required to complete the evaluation. Recent data also confirm that in older populations prevalence of malnutrition by this tool is associated with the level of dependence. The rationale of nutritional assessment is to identify patients candidate to nutritional support. However, the sensitivity of the MNA is still debated because it has been associated with a high-risk 'overdiagnosis' and the advantages of a positive screening need to be assessed both in terms of outcome and money saving. SUMMARY: The MNA is a simple and highly sensitive tool for nutritional screening and assessment. The large mass of data collected and the diffusion among healthcare professionals clearly support its use. However, the cost-effectiveness of interventions based on its scoring deserves investigation. PMID- 22037018 TI - Attentional biases in chronic pain: do they exist and does it really matter? PMID- 22037017 TI - Domain coupling in GPCRs: the engine for induced conformational changes. AB - Recent solved structures of G protein-coupled receptors (GPCRs) provide insights into variation of the structure and molecular mechanisms of GPCR activation. In this review, we provide evidence for the emerging paradigm of domain coupling facilitated by intrinsic disorder of the ligand-free state in GPCRs. The structure-function and dynamic studies suggest that ligand-bound GPCRs exhibit multiple active conformations in initiating cellular signals. Long-range intramolecular and intermolecular interactions at distant sites on the same receptor are crucial factors that modulate signaling function of GPCRs. Positive or negative coupling between the extracellular, the transmembrane and the intracellular domains facilitates cooperativity of activating 'switches' as requirements for the functional plasticity of GPCRs. Awareness that allosteric ligands robustly affect domain coupling provides a novel mechanistic basis for rational drug development, small molecule antagonism and GPCR regulation by classical as well as nonclassical modes. PMID- 22037019 TI - Modulation of mitochondrial respiratory capacity by carrier-mediated transfer of RNA in vivo. AB - Genetic dysfunction of mitochondria is pathological, but an effective method of nucleic acid delivery to mitochondria in vivo is lacking. Injection into rodents of tagged polycistronic RNAs (pcRNAs) encoding parts of the organelle genome and bound to a carrier complex, resulted in rapid uptake and concentration of the RNA in many tissues. The delivered RNA was localized to mitochondria. A pan-genomic cocktail of pcRNAs restored mRNA levels, stimulated mitochondrial translation and respiratory capacity of skeletal muscle of middle-aged and old rats. Thus, the carrier-based protocol may be suitable for delivery of functional RNAs to mitochondria in vivo. PMID- 22037020 TI - [Heart failure secondary to atrial tachycardia in the early phase of heart transplantation. Usefulness of the electrophysiological study]. PMID- 22037021 TI - Extracellular HspBP1 inhibits formation of a cytotoxic Tag7-Hsp70 complex in vitro and in human serum. AB - Tag7 (PGRP-S) was described as an innate immunity protein. Earlier we have shown that Tag7 forms with Hsp70 a stable complex with cytotoxic and antitumor activity. The same complex is formed in and secreted by cytotoxic T-lymphocytes. We have also found that Hsp-binding protein HspBP1 incapacitates the Tag7-Hsp70 complex. Here we have studied the interaction of extracellular Tag7 and HspBP1. We have shown that HspBP1 binds Tag7 in the conditioned medium of tumor CSML0 cells, thereby preventing formation of the cytotoxic Tag7-Hsp70 complex. We have also found that Tag7, if present in serum (in every third donor on average), is always in complex with HspBP1. This may be a protective measure against indiscriminate attack of the cytotoxic complex on normal cells. PMID- 22037022 TI - Targeting the mitochondrial pathway to induce apoptosis/necrosis through ROS by a newly developed Schiff's base to overcome MDR in cancer. AB - Multidrug resistance (MDR) in cancer, a major obstacle to successful application of cancer chemotherapy, is often characterized by over-expression of multidrug resistance-related proteins such as MRP1, P-gp or elevated glutathione (GSH) level. Efflux of drugs by functional P-gp, MRP1 and elevated GSH level can confer resistance to apoptosis induced by a range of different stimuli. Therefore, it is necessary to develop new cell death inducers with relatively lower toxicity toward non-malignant cells that can overcome MDR by induction of apoptotic or non apoptotic cell death pathways. Herein we report the synthesis and spectroscopic characterization of a GSH depleting, redox active Schiff's base, viz., potassium N-(2-hydroxy-3-methoxy-benzaldehyde)-alaninate (PHMBA). Cytotoxic potential of PHMBA has been studied in doxorubicin-resistant and -sensitive T lymphoblastic leukemia cells and Ehrlich ascites carcinoma (EAC) cells. PHMBA kills both the cell types irrespective of their drug-resistance phenotype following apoptotic/necrotic pathways. Moreover, PHMBA-induced cell death is associated with oxidative stress mediated mitochondrial pathway as the H(2)O(2) inhibitor PEG-Catalase abrogated PHMBA-induced apoptosis/necrosis. PHMBA induces anti-tumor activity in both doxorubicin-sensitive and -resistant EAC-tumor-bearing Swiss albino mice. The non-toxicity of PHMBA was also confirmed through cytotoxicity studies on normal cell lines like PBMC, NIH3T3 and Chang Liver. To summarise, our data provide compelling rationale for future clinical use of this redox active Schiff's base in treatment of cancer patients irrespective of their drug resistance status. PMID- 22037023 TI - Methods to produce and safely work with large numbers of Toxoplasma gondii oocysts and bradyzoite cysts. AB - Two major obstacles to conducting studies with Toxoplasma gondii oocysts are the difficulty in reliably producing large numbers of this life stage and safety concerns because the oocyst is the most environmentally resistant stage of this zoonotic organism. Oocyst production requires oral infection of the definitive feline host with adequate numbers of T. gondii organisms to obtain unsporulated oocysts that are shed in the feces for 3-10 days after infection. Since the most successful and common mode of experimental infection of kittens with T. gondii is by ingestion of bradyzoite tissue cysts, the first step in successful oocyst production is to ensure a high bradyzoite tissue cyst burden in the brains of mice that can be used for the oral inoculum. We compared two methods for producing bradyzoite brain cysts in mice, by infecting them either orally or subcutaneously with oocysts. In both cases, oocysts derived from a low passage T. gondii Type II strain (M4) were used to infect eight-ten week-old Swiss Webster mice. First the number of bradyzoite cysts that were purified from infected mouse brains was compared. Then to evaluate the effect of the route of oocyst inoculation on tissue cyst distribution in mice, a second group of mice was infected with oocysts by one of each route and tissues were examined by histology. In separate experiments, brains from infected mice were used to infect kittens for oocyst production. Greater than 1.3 billion oocysts were isolated from the feces of two infected kittens in the first production and greater than 1.8 billion oocysts from three kittens in the second production. Our results demonstrate that oral delivery of oocysts to mice results in both higher cyst loads in the brain and greater cyst burdens in other tissues examined as compared to those of mice that received the same number of oocysts subcutaneously. The ultimate goal in producing large numbers of oocysts in kittens is to generate adequate amounts of starting material for oocyst studies. Given the potential risks of working with live oocysts in the laboratory, we also tested a method of oocyst inactivation by freeze-thaw treatment. This procedure proved to completely inactivate oocysts without evidence of significant alteration of the oocyst molecular integrity. PMID- 22037024 TI - Enhancing liver mitochondrial fatty acid oxidation capacity in obese mice improves insulin sensitivity independently of hepatic steatosis. AB - BACKGROUND & AIMS: Despite major public health concern, therapy for non-alcoholic fatty liver, the liver manifestation of the metabolic syndrome often associated with insulin resistance (IR), remains elusive. Strategies aiming to decrease liver lipogenesis effectively corrected hepatic steatosis and IR in obese animals. However, they also indirectly increased mitochondrial long-chain fatty acid oxidation (mFAO) by decreasing malonyl-CoA, a lipogenic intermediate, which is the allosteric inhibitor of carnitine palmitoyltransferase 1 (CPT1A), the key enzyme of mFAO. We thus addressed whether enhancing hepatic mFAO capacity, through a direct modulation of liver CPT1A/malonyl-CoA partnership, can reverse an already established hepatic steatosis and IR in obese mice. METHODS: Adenovirus-mediated liver expression of a malonyl-CoA-insensitive CPT1A (CPT1mt) in high-fat/high-sucrose (HF/HS) diet-induced or genetically (ob/ob) obese mice was followed by metabolic and physiological investigations. RESULTS: In association with increased hepatic mFAO capacity, liver CPT1mt expression improved glucose tolerance and insulin response to a glucose load in HF/HS and ob/ob mice, showing increased insulin sensitivity, and corrected IR in ob/ob mice. Surprisingly, hepatic steatosis was not affected in CPT1mt-expressing obese mice, indicating a clear dissociation between hepatic steatosis and IR. Moreover, liver CPT1mt expression rescued HF/HS-induced impaired hepatic insulin signaling at the level of IRS-1, IRS-2, Akt, and GSK-3beta, most likely through the observed decrease in the HF/HS-induced accumulation of lipotoxic lipids, oxidative stress, and JNK activation. CONCLUSIONS: Enhancing hepatic mFAO capacity is sufficient to reverse a state of IR and glucose intolerance in obese mice independently of hepatic steatosis. PMID- 22037025 TI - PPARalpha is down-regulated following liver transplantation in mice. AB - BACKGROUND & AIMS: Graft dysfunction is one of the major complications after liver transplantation, but its precise mechanism remains unclear. Since steatotic liver grafts are susceptible to post-transplant dysfunction, and peroxisome proliferator-activated receptor (PPAR) alpha plays an important role in the maintenance of hepatic lipid homeostasis, we examined the role of PPARalpha in liver transplantation. METHODS: Livers were harvested from Sv/129 wild-type (Ppara(+/+)) mice and PPARalpha-null (Ppara(-/-)) mice and transplanted orthotopically into syngeneic Ppara(+/+) mice. RESULTS: Hepatocellular damage was unexpectedly milder in transplanted Ppara(-/-) livers compared with Ppara(+/+) ones. This was likely due to decreased lipid peroxides in the Ppara(-/-) livers, as revealed by the lower levels of fatty acid oxidation (FAO) enzymes, which are major sources of reactive oxygen species. Hepatic PPARalpha and its target genes, such as FAO enzymes and pyruvate dehydrogenase kinase 4, were strongly down regulated after transplantation, which was associated with increases in hepatic tumor necrosis factor-alpha expression and nuclear factor-kappaB activity. Inhibiting post-transplant PPARalpha down-regulation by clofibrate treatment markedly augmented oxidative stress and hepatocellular injury. CONCLUSIONS: Down regulation of PPARalpha seemed to be an adaptive response to metabolic alterations following liver transplantation. These results provide novel information to the understanding of the pathogenesis of early post-transplant events. PMID- 22037026 TI - Clinical pharmacology as a cornerstone of orphan drug development. AB - A recent US Food and Drug Administration (FDA) advisory committee meeting highlighted the potential of clinical pharmacology to overcome challenges in orphan drug development. PMID- 22037027 TI - Accelerated approval dust begins to settle. PMID- 22037028 TI - Buy buy bispecific antibodies. PMID- 22037031 TI - David Urdal. Interview with Asher Mullard. PMID- 22037032 TI - The depression market. PMID- 22037033 TI - Vemurafenib. AB - In August 2011 vemurafenib (Zelboraf; Daiichi Sankyo/Roche), an inhibitor of BRAF kinase, was approved by the US Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma with the BRAF(V600E) mutation. PMID- 22037034 TI - Vaccines: Protecting against tuberculosis. PMID- 22037035 TI - Cancer: Oncolytic poxvirus homes in on cancer cells. PMID- 22037036 TI - Inflammatory diseases: Stopping monocytes in their tracks. PMID- 22037040 TI - Quantifying factors for the success of stratified medicine. AB - Co-developing a drug with a diagnostic to create a stratified medicine - a therapy that is targeted to a specific patient population on the basis of a clinical characteristic such as a biomarker that predicts treatment response - presents challenges for product developers, regulators, payers and physicians. With the aim of developing a shared framework and tools for addressing these challenges, here we present an analysis using data from case studies in oncology and Alzheimer's disease, coupled with integrated computational modelling of clinical outcomes and developer economic value, to quantify the effects of decisions related to key issues such as the design of clinical trials. This illustrates how such analyses can aid the coordination of diagnostic and drug development, and the selection of optimal development and commercialization strategies. It also illustrates the impact of the interplay of these factors on the economic feasibility of stratified medicine, which has important implications for public policy makers. PMID- 22037042 TI - Striatal inhibition of calpains prevents levodopa-induced neurochemical changes and abnormal involuntary movements in the hemiparkinsonian rat model. AB - Pharmacological dopamine replacement with l-3,4-dihydroxyphenylalanine (L-DOPA) remains the most effective approach to treat the motor symptoms of Parkinson's disease (PD). However, as the disease progresses, the therapeutic response to L DOPA gradually becomes erratic and is associated with the emergence of dyskinesia in the majority of patients. The pathogenesis of L-DOPA-induced dyskinesia (LID) is still unknown. In the current study, using the 6-hydroxydopamine (6-OHDA) lesioned rat model of PD, we demonstrated that the calcium-dependent proteins calpains and cdk5 of the striatum play a critical role in the behavioral and molecular changes evoked by L-DOPA therapy. We first confirmed that L-DOPA reversed PD symptoms, assessed by the cylinder, stepping and vibrissae-elicited reaching tests in this animal model, and elicited robust abnormal involuntary movements (AIMs) reminiscent of LID. Interestingly, intrastriatal infusion of the calpains inhibitor MDL28170, and to a lower extent the cdk5 inhibitor roscovitine, reduced the severity and amplitude of AIMs without affecting L DOPA's antiparkinsonian effects. Notably, the calpains and cdk5 inhibitors totally reversed the striatal molecular changes attributed to L-DOPA therapy, such as ERK1/2 and dynamin phosphorylation. Another fascinating observation was that L-DOPA therapy, in combination with intrastriatal infusion of MDL28170, augmented tyrosine hydroxylase levels in the striatum of lesioned rats without affecting the number of dopaminergic cells in the substantia nigra. These findings disclose a novel mechanism underlying the maladaptive alterations induced by L-DOPA therapy in the 6-OHDA rat model of PD. PMID- 22037043 TI - Fatal fulminant primary hepatitis B virus infections with G1896A precore viral mutants in southeastern France. AB - Fulminant hepatitis has been shown to occur in about 1% of acute hepatitis B virus (HBV) infections, and its mortality rate is nearly 70%. Specific HBV genotypic features have been pointed out in fulminant acute hepatitis B worldwide, but these associations remain controversial. We describe all four primary HBV infections diagnosed in 2008 in our institution in Marseille, southeastern France, including two fatal cases. HBV genotypes were D or E. Precore G1896A HBV mutants were detected in both fatal fulminant primary HBV infections. Hepatitis B surface antigen and hepatitis B e antigen (HBeAg) were negative in two and three cases, respectively, despite HBV DNA detection. Primary HBV infection remains a cause of death in France. The impact of the precore G1896A mutation on the severity of AHB deserves to be assessed in larger studies in this country. PMID- 22037041 TI - Rapamycin passes the torch: a new generation of mTOR inhibitors. AB - Mammalian target of rapamycin (mTOR) is an atypical protein kinase that controls growth and metabolism in response to nutrients, growth factors and cellular energy levels, and it is frequently dysregulated in cancer and metabolic disorders. Rapamycin is an allosteric inhibitor of mTOR, and was approved as an immuno-suppressant in 1999. In recent years, interest has focused on its potential as an anticancer drug. However, the performance of rapamycin and its analogues (rapalogues) has been undistinguished despite isolated successes in subsets of cancer, suggesting that the full therapeutic potential of targeting mTOR has yet to be exploited. A new generation of ATP-competitive inhibitors that directly target the mTOR catalytic site display potent and comprehensive mTOR inhibition and are in early clinical trials. PMID- 22037044 TI - New Markov-Shannon Entropy models to assess connectivity quality in complex networks: from molecular to cellular pathway, Parasite-Host, Neural, Industry, and Legal-Social networks. AB - Graph and Complex Network theory is expanding its application to different levels of matter organization such as molecular, biological, technological, and social networks. A network is a set of items, usually called nodes, with connections between them, which are called links or edges. There are many different experimental and/or theoretical methods to assign node-node links depending on the type of network we want to construct. Unfortunately, the use of a method for experimental reevaluation of the entire network is very expensive in terms of time and resources; thus the development of cheaper theoretical methods is of major importance. In addition, different methods to link nodes in the same type of network are not totally accurate in such a way that they do not always coincide. In this sense, the development of computational methods useful to evaluate connectivity quality in complex networks (a posteriori of network assemble) is a goal of major interest. In this work, we report for the first time a new method to calculate numerical quality scores S(L(ij)) for network links L(ij) (connectivity) based on the Markov-Shannon Entropy indices of order k-th (theta(k)) for network nodes. The algorithm may be summarized as follows: (i) first, the theta(k)(j) values are calculated for all j-th nodes in a complex network already constructed; (ii) A Linear Discriminant Analysis (LDA) is used to seek a linear equation that discriminates connected or linked (L(ij)=1) pairs of nodes experimentally confirmed from non-linked ones (L(ij)=0); (iii) the new model is validated with external series of pairs of nodes; (iv) the equation obtained is used to re-evaluate the connectivity quality of the network, connecting/disconnecting nodes based on the quality scores calculated with the new connectivity function. This method was used to study different types of large networks. The linear models obtained produced the following results in terms of overall accuracy for network reconstruction: Metabolic networks (72.3%), Parasite Host networks (93.3%), CoCoMac brain cortex co-activation network (89.6%), NW Spain fasciolosis spreading network (97.2%), Spanish financial law network (89.9%) and World trade network for Intelligent & Active Food Packaging (92.8%). In order to seek these models, we studied an average of 55,388 pairs of nodes in each model and a total of 332,326 pairs of nodes in all models. Finally, this method was used to solve a more complicated problem. A model was developed to score the connectivity quality in the Drug-Target network of US FDA approved drugs. In this last model the theta(k) values were calculated for three types of molecular networks representing different levels of organization: drug molecular graphs (atom-atom bonds), protein residue networks (amino acid interactions), and drug-target network (compound-protein binding). The overall accuracy of this model was 76.3%. This work opens a new door to the computational reevaluation of network connectivity quality (collation) for complex systems in molecular, biomedical, technological, and legal-social sciences as well as in world trade and industry. PMID- 22037045 TI - Stable trimorphic coexistence in a lattice model of spatial competition with two site types. AB - I examine the effect of exogenous spatial heterogeneity on the coexistence of competing species using a simple model of non-hierarchical competition for site occupancy on a lattice. The sites on the lattice are divided into two types representing two different habitats or spatial resources. The model features no temporal variability, hierarchical competition, type-dependent interactions or other features traditionally known to support more competing species than there are resources. Nonetheless, stable coexistence of two habitat specialists and a generalist is observed in this model for a range of parameter values. In the spatially implicit mean field approximation of the model, such coexistence is shown to be impossible, demonstrating that it indeed arises from the explicit spatial structure. PMID- 22037046 TI - Multi-kernel transfer learning based on Chou's PseAAC formulation for protein submitochondria localization. AB - Protein sub-organelle localization, e.g. submitochondria, seems more challenging than general protein subcellular localization, because the determination of protein's micro-level localization within organelle by fluorescent imaging technique would face up with more difficulties. Up to present, there are far few computational methods for protein submitochondria localization, and the existing sequence-based predictive models demonstrate moderate or unsatisfactory performance. Recent researches have demonstrated that gene ontology (GO) is a convincingly effective protein feature for protein subcellular localization. However, the GO information may not be available for novel proteins or sparsely annotated protein subfamilies. In allusion to the problem, we transfer the homology's GO information to the target protein and propose a multi-kernel transfer learning model for protein submitochondria localization (MK-TLM), which substantially extends our previously published work (gene ontology based transfer learning model for protein subcellular localization, GO-TLM). To reduce the risk of performance overestimation, we conduct a more comprehensive survey of the model performance in optimistic case, moderate case and pessimistic case according to the abundance of target protein's GO information. The experiments on submitochondria benchmark datasets show that MK-TLM significantly outperforms the baseline models, and demonstrates excellent performance for novel mitochondria proteins and those mitochondria proteins that belong to the subfamily we know little about. PMID- 22037047 TI - (2-Benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-8-yl)-acetic acid: an aldose reductase inhibitor and antioxidant of zwitterionic nature. AB - Novel carboxymethylated pyridoindoles, characterized by antioxidant activity combined with the ability to inhibit aldose reductase, represent an example of a multitarget approach to the treatment of diabetic complications - severe diabetes related health disorders of multifunctional nature. One of the novel carboxymethylated pyridoindoles, (2-benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3 b]indol-8-yl)-acetic acid (compound 1), was found to inhibit aldose reductase with the IC(50) value 18.2 +/- 1.2 MUM. Owing to aldose reductase pharmacophore requirements for an acidic proton, most aldose reductase inhibitors contain an acetic acid moiety, ionized at physiological pH, resulting in poor bioavailability of the drugs. The presence of a basicity center at the tertiary nitrogen of the carboxymethylated pyridoindoles, in addition to the acidic carboxylic function, predisposes these compounds to form double-charged zwitterionic species. The zwitterionic nature of compound 1 may remarkably affect its pH-lipophilicity profile allowing for increased membrane penetration in the pH region around its isoelectric point, which lies close to the physiological pH 7.4. In the first part of this study, the presence of zwitterionic species was experimentally proved by the concentration-dependent effect of sodium 1 hexanesulphonate on the distribution profile of compound 1. Then a series of experiments was performed in the cellular system of isolated erythrocytes in vitro. Isolated rat erythrocytes exposed to peroxyl radicals, generated in the solution by decomposition of the hydrophilic azoinitiator AAPH or intracellularly by decay of lipophilic t-BuOOH, underwent progressive hemolysis. The onset of the hemolysis was shifted from the starting zero point by the time interval assigned as a lag period. In the presence of compound 1 the lag period was significantly prolonged. Finally, under conditions of a short-term experiment in STZ-diabetic rats in vivo, increase in sorbitol levels in erythrocytes was recorded. Compound 1 administered in the dose 50mg/kg/day (i.g.) significantly decreased the sorbitol level in the erythrocytes. To conclude, the physico-chemical proof of the zwitterionic nature of compound 1 was established and the results obtained in isolated red blood cells indicated good cellular availability of the compound. In addition, in diabetic rats, sorbitol accumulation in red blood cells was significantly inhibited by compound 1 administered intra-gastrically, suggesting its ready uptake into the central compartment. The zwitterionic principle thus may have significant consequences for increased bioavailability of drugs bearing an acidic function. PMID- 22037048 TI - Synthesis of deguelin-biotin conjugates and investigation into deguelin's interactions. AB - Deguelin, a rotenoid, has emerged as an attractive pharmacophore for chemoprevention showing in vivo activity in several xenografts. Recently, several lines of evidence have suggested its mode of action may involve inhibition of HSP90, however binding in a different mode than known pharmacophores. To further probe the target of deguelin and related rotenoids, several biotin conjugates were prepared. None of the conjugates showed significant affinity for HSP90, however two conjugates showed a strong cellular co-localization with mitochondria, consistent with binding to mitochondrial complex 1. Contrarily to rotenone, deguelin and tephrosin were not found to inhibit tubulin polymerization demonstrating a dramatic pharmacological difference between these closely related rotenoids. PMID- 22037050 TI - Design, synthesis and biological evaluation of cycloalkyl arylpyrimidines (CAPYs) as HIV-1 NNRTIs. AB - A series of 18 cycloalkyl arylpyrimidines (CAPYs) were designed from lead compounds diarylpyrimidines (DAPYs), synthesized and evaluated for in vitro anti HIV activity. Among them, the compound 1p displayed potent anti-HIV-1 activity against WT HIV-1 with an EC(50) value of 0.055 MUM and a selectivity index (SI) >7290. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated, which enriched the SAR of diarylpyrimidines (DAPYs). PMID- 22037049 TI - Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class. AB - The demonstrated ability of amphetamine to functionally activate the rat trace amine associated receptor 1 (rTAAR1) and the subsequent reports of amphetamine activation of TAAR1 in rhesus monkey mouse, human, and human-rat chimeric TAAR1 expressing cell lines has led to speculation as to the role of this receptor in the central nervous system (CNS) responses associated with amphetamine and its analogs. The agonist potencies of ten pairs of enantiomeric amphetamines, including several with known CNS activity, at primate TAAR1 stably expressed in RD-HGA16 cells, robustly indicate the S-configuration to be associated with higher potency. Moreover, the rank order of potency to activate TAAR1 parallels the stimulant action reported by humans for the specific amphetamines. Taken together, these data suggest that TAAR1 is a stereoselective binding site for amphetamine and that activation of TAAR1 is involved in the modulation of the stimulant properties of amphetamine and its congeners. In addition, the observed parallel between hTAAR1 and rhTAAR1 responses supports the rhesus monkey as a highly translational model for developing novel TAAR1-directed compounds as therapeutics for amphetamine-related addictions. PMID- 22037051 TI - Establishment of a novel objective and quantitative method to assess pain-related behavior in monosodium iodoacetate-induced osteoarthritis in rat knee. AB - INTRODUCTION: Pain in osteoarthritis (OA) patients can be present at rest but typically worsens with movement of the affected joint. However, useful assessment methods of movement-induced pain in animal models are limited. Here, we describe the reduction of spontaneous activity in a rat model of OA as an objective and quantifiable behavioral pain that can predict the analgesic activity of a variety of agents following single-dose administration. METHODS: OA was induced in male Sprague-Dawley (SD) rats by intra-articular injection of monoiodoacetate (MIA), and the joint degeneration was assessed with histologic and radiographic analyses. Spontaneous activities were measured in nonhabituated rats using standard, photocell-based monitor systems in the dark. To investigate the potential of the OA model to predict analgesic activity, a number of nonsteroidal anti-inflammatory drugs (NSAIDs) and atypical analgesic drugs were used. RESULTS: Biphasic reduction of total distance and number of rears was observed during the course of experiment after administering 1mg and 0.3mg of MIA, respectively. We found that number of rears was the most sensitive to MIA-induce OA and displayed the greatest percentage decrease in activity. Joint degeneration was observed with decreased bone mineral density and loss of articular cartilage 28days post MIA injection. Appropriate dosage of opioids reversed MIA-induced decrease of number of rears indicating that reduction of this vertical spontaneous activity reflects pain-associated behavior. As high-doses of opioids reduced spontaneous activity, the sedative effect can be distinguished from the analgesic effect. Analgesic treatment indicates the coexistence of an inflammatory pain state (early phase) sensitive to NSAIDs and a non-inflammatory pain state (late phase) resistant to NSAID treatment. DISCUSSION: This study indicates that unlike standard measures of analgesia such as alteration in thermal or mechanical sensitivity, measurement of spontaneous activity is a validated method for measuring the effects of analgesics in rats with OA knee joints. Moreover, the animals require no habituation, and thus behavioral observation subjectivity is eliminated. PMID- 22037052 TI - Eritrean and Sudanese migrants presenting with malaria in Israel. AB - In Israel, a malaria-free country, we have noticed lately an increase of hospital admissions with malaria, parallel to the rise in the number of Eritrean and Sudanese migrants. Eritrea and Sudan are malaria-endemic countries; Plasmodium falciparum accounts for 85-90% and Plasmodium vivax accounts for 10-15% of malaria species in these areas. We aimed to describe the features of malaria in this migrant population by conducting a retrospective descriptive study of Eritrean and Sudanese migrants admitted with malaria during 1/2009-4/2010. Patient files were reviewed for demographics, clinical data, laboratory tests, treatment and outcome. 101 patients (mean age 24.9 (SD 5.6) years; 86.1% males) with malaria were identified. 87.1% were infected with P. vivax, 6% with P. falciparum, and 6.9% had both. All presented with pyrexia. None had respiratory or cerebral complications. Mean length of hospitalization was 2.49 (SD 1.5) days. No treatment failures or complications were observed. We conclude that in countries with waves of migrants from malaria-endemic areas, onset of fever should raise suspicion of malaria. Contrary to the known dominance of P. falciparum among malaria species in Eritrea and Sudan, the vast majority of migrants presented with P. vivax. The region of P. vivax acquisition remains unclear. PMID- 22037053 TI - Travel clinic communication and non-adherence to malaria chemoprophylaxis. AB - Many travellers fail to take malaria chemoprophylaxis, despite receiving pre travel advice. This study examined whether non-adherence could be predicted from verbal communication in the pre-travel consultation, and whether non-adherence was related to the quality of clinician-traveller communication. The consultations of one hundred and thirty consecutive travellers at a UK travel clinic were audiotaped and a follow-up telephone interview was used to assess adherence to malaria chemoprophylaxis. Experienced travel clinic staff were asked to predict adherence and rate the quality of communication from eighteen transcripts of consultations (nine good and nine poor adherence). Clinic staff predicted adherence to malaria chemoprophylaxis significantly better than chance. Poor adherence was related to poor quality communication. Clinic staff provided criteria for good quality clinician-traveller communication. It is concluded that predictors of non-adherence can be identified during the pre-travel consultation. Clinic staff could employ specific communication strategies to improve the effectiveness of consultations. PMID- 22037054 TI - Anti-ferroelectric polarization transitions in quantum-dot-quantum-well arrays. AB - With the improvement in fabrication techniques it is now possible to produce atom like semiconductor structures with unique electronic properties. This makes possible periodic arrays of nanostructures in which the Coulomb interaction, polarizability and tunneling may all be varied. This theoretical study investigates the collective properties of 2D arrays and 3D face-centered cubic lattices of singly charged nanospherical shells, sometimes called 'quantum dot quantum wells' or 'core-shell quantum dots'. We find that, for square arrays, the classical ground state is an Ising anti-ferroelectric (AFE), while the quantum ground state undergoes a transition from a uniform state to an AFE. The triangular lattice, in contrast, displays properties characteristic of frustration. Three-dimensional face-centered cubic lattices polarize in planes, with each layer alternating in direction. We discuss the possible experimental signals of these transitions. PMID- 22037055 TI - Can genetic risk information for age-related macular degeneration influence motivation to stop smoking? A pilot study. AB - AIMS: Smoking can increase the risk of macular degeneration and this is more than additive if a person also has a genetic risk. The purpose of this study was to examine whether knowledge of genetic risk for age-related macular degeneration (AMD) could influence motivation to quit smoking. METHODS: A questionnaire-based study of hypothetical case scenarios given to 49 smokers without AMD. Participants were randomly allocated to a generic risk, high genetic risk, or low genetic risk of developing AMD scenario. RESULTS: Forty-seven percent knew of the link between smoking and eye disease. In all, 76%, 67%, and 46% for the high risk, generic, and low risk groups, respectively, would rethink quitting (P for trend = 0.082). In all, 67%, 40%, and 38.5%, respectively, would be likely, very likely, or would definitely quit in the following month (P for trend = 0.023). Few participants (<16% of any group) were very likely to or would definitely attend a quit smoking session with no difference across groups. In all, 75.5% of participants would consider taking a genetic test for AMD. CONCLUSION: In this pilot study, a trend was seen for the group given high genetic risk information to be more likely to quit than the generic or low genetic risk groups. Participants were willing to take a genetic test but further work is needed to address the cost benefits of routine genetic testing for risk of AMD. More generic risk information should be given to the public, and health warnings on cigarette packets that 'smoking causes blindness' is a good way to achieve this. PMID- 22037056 TI - A step-by-step guide to systematically identify all relevant animal studies. AB - Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future. PMID- 22037057 TI - Coping with parvovirus infections in mice: health surveillance and control. AB - Parvoviruses of mice, minute virus of mice (MVM) and mouse parvovirus (MPV), are challenging pathogens to eradicate from laboratory animal facilities. Due to the impediment on rodent-based research, recent studies have focused on the assessment of re-derivation techniques and parvoviral potential to induce persistent infections. Summarizing recent data, this review gives an overview on studies associated with parvoviral impact on research, diagnostic methods, parvoviral persistence and re-derivation techniques, demonstrating the complex nature of parvovirus infection in mice and unfolding the challenge of controlling parvovirus infections in laboratory animal facilities. PMID- 22037058 TI - Effects of endokinin A/B, endokinin C/D, and endomorphin-1 on the regulation of mean arterial blood pressure in rats. AB - Endokinins are four novel human tachykinins, including endokinins A (EKA), B (EKB), C (EKC), and D (EKD). Endokinin A/B (EKA/B) is the common C-terminal decapeptide in EKA and EKB, while endokinin C/D (EKC/D) is the common C-terminal duodecapeptide in EKC and EKD. In this study, we attempted to investigate the interactions between EKA/B, EKC/D, and endomorphin-1 (EM-1) on the depressor effect at peripheral level. The effects of EKA/B produced a U-shaped curve. The maximal effect was caused by 10 nmol/kg. EKC/D and EM-1 showed a dose-dependent relationship. Co-administration of EKA/B (0.1, 1, 10 nmol/kg) with EM-1 produced effects similar to those of EKA/B alone but slightly lower. Co-injection of EKA/B (100 nmol/kg) with EM-1 caused an effect stronger than any separate injection. Co administration of EKC/D (10 nmol/kg) with EM-1 (30 nmol/kg) caused a depressor effect, which was one of the tradeoffs of EM-1 and EKC/D. Mechanism studies showed that SR140333B could block the depressor effects of EKA/B, EKC/D, EM-1, EKA/B+EM-1, and EKC/D+EM-1; SR48968C could block EM-1, EKA/B, EKC/D, and EKC/D+EM 1 and partially block EKA/B+EM-1; SR142801 could block EM-1, EKC/D, and EKC/D+EM 1 and partially block EKA/B and EKA/B+EM-1; naloxone could block EM-1, EKC/D, and EKC/D+EM-1 and partially block EKA/B and EKA/B+EM-1. Pretreatment with NG-nitro-l arginine methyl ester partially decreased depressor intensity and half-recovery time of EKA/B and EKC/D. PMID- 22037059 TI - Differential detection of Trichinella papuae, T. spiralis and T. pseudospiralis by real-time fluorescence resonance energy transfer PCR and melting curve analysis. AB - Trichinellosis caused by nematodes of Trichinella spp. is a zoonotic foodborne disease. Three Trichinella species of the parasite including Trichinella spiralis, Trichinella papuae and Trichinella pseudospiralis, have been etiologic agents of human trichinellosis in Thailand. Definite diagnosis of this helminthiasis is based on a finding of the Trichinella larva (e) in a muscle biopsy. The parasite species or genotype can be determined using molecular methods, e.g., polymerase chain reaction (PCR). This study has utilized real-time fluorescence resonance energy transfer PCR (real-time FRET PCR) and a melting curve analysis for the differential diagnosis of trichinellosis. Three common Trichinella species in Thailand were studied using one set of primers and fluorophore-labeled hybridization probes specific for the small subunit of the mitochondrial ribosomal RNA gene. Using fewer than 35 cycles as the cut-off for positivity and using different melting temperatures (T(m)), this assay detected T. spiralis, T. papuae and T. pseudospiralis in muscle tissue and found the mean T(m) +/- SD values to be 51.79 +/- 0.06, 66.09 +/- 0.46 and 51.46 +/- 0.09, respectively. The analytical sensitivity of the technique enabled the detection of a single Trichinella larva of each species, and the detection limit for the target DNA sequence was 16 copies of positive control plasmid. A test of the technique's analytical specificity showed no fluorescence signal for a panel of 19 non-Trichinella parasites or for human and mouse genomic DNA. Due to the sensitivity and specificity of the detection of these Trichinella species, as well as the fast and high-throughput nature of these tools, this method has application potential in differentiating non-encapsulated larvae of T. papuae from T. spiralis and T. pseudospiralis in tissues of infected humans and animals. PMID- 22037060 TI - Neutrophil dynamics in response to chemotherapy and G-CSF. AB - We have used a mathematical model of the combined dynamics of the hematopoietic stem cells and the differentiated neutrophil progeny to examine the effects of periodic chemotherapy in generating neutropenia, and the corresponding response of this system to granulocyte colony stimulating factor given to counteract the neutropenia. We find that there is a significant period of chemotherapy delivery that induces resonance in the system (at a period twice the average neutrophil lifespan from commitment to death) and a corresponding neutropenia suggesting that myelosuppressive protocols should avoid this period to minimize hematopoietic damage. The response to G-CSF is highly variable. PMID- 22037061 TI - Elastic and viscoelastic properties of a type I collagen fiber. AB - A new mathematical model is presented to describe the elastic and viscoelastic properties of a single collagen fiber. The model is formulated by accounting for the mechanical contribution of the collagen fiber's main constituents: the microfibrils, the interfibrillar matrix and crosslinks. The collagen fiber is modeled as a linear elastic spring, which represents the mechanical contribution of the microfibrils, and an arrangement in parallel of elastic springs and viscous dashpots, which represent the mechanical contributions of the crosslinks and interfibrillar matrix, respectively. The linear elastic spring and the arrangement in parallel of elastic springs and viscous dashpots are then connected in series. The crosslinks are assumed to gradually break under strain and, consequently, the interfibrillar is assumed to change its viscous properties. Incremental stress relaxation tests are conducted on dry collagen fibers reconstituted from rat tail tendons to determine their elastic and viscoelastic properties. The elastic and total stress-strain curves and the stress relaxation at different levels of strain collected by performing these tests are then used to estimate the parameters of the model and evaluate its predictive capabilities. PMID- 22037062 TI - Prediction of protein-protein interaction sites using patch-based residue characterization. AB - Identifying protein-protein interaction sites provides important clues to the function of a protein and is becoming increasingly relevant in topics such as systems biology and drug discovery. Using a patch-based model for residue characterization, we trained random forest classifiers for residue-based interface prediction, which was followed by a clustering procedure to produce patches for patch-based interface prediction. For residue-based interface prediction, our method achieves a specificity rate of 0.7 and a sensitivity rate of 0.78. For patch-based interface prediction, a success rate of 0.80 is achieved. Based on same datasets, we also compare it with several published methods. The results show that our method is a successful predictor for residue based and patch-based interface prediction. PMID- 22037063 TI - Evolution of cooperation facilitated by reinforcement learning with adaptive aspiration levels. AB - Repeated interaction between individuals is the main mechanism for maintaining cooperation in social dilemma situations. Variants of tit-for-tat (repeating the previous action of the opponent) and the win-stay lose-shift strategy are known as strong competitors in iterated social dilemma games. On the other hand, real repeated interaction generally allows plasticity (i.e., learning) of individuals based on the experience of the past. Although plasticity is relevant to various biological phenomena, its role in repeated social dilemma games is relatively unexplored. In particular, if experience-based learning plays a key role in promotion and maintenance of cooperation, learners should evolve in the contest with nonlearners under selection pressure. By modeling players using a simple reinforcement learning model, we numerically show that learning enables the evolution of cooperation. We also show that numerically estimated adaptive dynamics appositely predict the outcome of evolutionary simulations. The analysis of the adaptive dynamics enables us to capture the obtained results as an affirmative example of the Baldwin effect, where learning accelerates the evolution to optimality. PMID- 22037064 TI - Probable autoimmune causal relationship between periodontitis and Hashimotos thyroidits: a systemic review. AB - Periodontitis is a multifactorial disease with microbial dental plaque as the initiator of periodontal disease. However, the manifestation and progression of the disease is influenced by a wide variety of determinants and factors. The strongest type of causal relationship is the association of systemic and periodontal disease. Hashimotos thyroiditis has also been considered as one of the causes of periodontal disease. As a matter of fact, on an autoimmune basis, in Hashimotos disease and periodontal disease, we have made an attempt to derive the common mechanisms, with an evidence base. The need for this kind of review was due to the fact that the outcome of periodontal therapy did not give the expected results in patients with Hashimoto's thyroiditis. Hence, a possible link between Hashimotos thyroiditis and periodontitis was considered. PMID- 22037065 TI - Classification and management challenges of otitis media in a resource-poor country. AB - The clinical features and sequelae of otitis media (OM) vary depending on the duration, severity and progression of the disease. As a result, opinions on the modes of classification and management protocols have differed over the years. The need to critically appraise these opinions according to the peculiarities of each region is imperative. This work was aimed at reviewing the world literature on the subject and also highlights the limitations in management in our region. A wide literature search was conducted using the following search engines: PubMed, AJOL and University of Toronto Library. Also incorporated were essential materials obtained from the authors' clinical practices. The search engines returned 22,903 related articles on OM. Further filtration yielded 88 articles on "classification and management" and these were obtained in full and thoroughly read. Extracted materials for review spanned between 1980 and 2008. OM is prevalent the world over with potentially severe complications if inadequately managed, especially in the developing countries. It is of note that in the developing countries, poverty, ignorance, dearth of specialists and limited access to medical care amongst others conspire to worsen the course and complications of OM. PMID- 22037066 TI - The status of tuberculosis infection control measures in health care facilities rendering joint TB/HIV services in "German Leprosy and Tuberculosis Relief Association" supported states in Nigeria. AB - OBJECTIVE: To assess the status of tuberculosis (TB) infection control practice in health care facilities implementing joint TB/HIV activities. MATERIALS AND METHODS: A descriptive survey triangulating self-administered questionnaire (facility survey to Infection Control Officer, individual health worker to general health workers), review of facility case notes and participant observation techniques was carried out. Twelve health facilities from southern Nigeria were assessed. RESULTS: (1) Administrative and work practice control measure: Only 1 (8.3%) facility had a documented TB Infection control policy; 2 (16.7%) facilities had Infection Control Committee; 5 (41.7%) facilities had Infection Control Officer; 2 (16.7%) asked questions at the health records about cough; 1 (8.3%) facility had health workers intermittently checking for patients with cough in the waiting hall; and 2 (16.7%) facilities had Infection Control Officers who have attended some training on infection control. No facility had Information, Education and Communication (IEC) materials reminding patients and health workers of the possibility of TB transmission in the health care setting. While 86.4% of TB patients were screened for HIV, only 54.7% of HIV patients were tested for TB. (2) Environmental control measures: All the waiting halls were well ventilated. Though 66.7% of the consulting rooms were well ventilated, 25% of them were over crowded; 58.3% of the facilities managed sputum smear positive TB patients in the same ward with HIV-positive and other vulnerable patients; no facility had air cleaners. CONCLUSION: Implementation of the different aspects of the administrative control and work practice component of TB infection control measure range from 8.3% to 41.7% of the facilities. Urgent measures should be taken to reverse this trend in the face of TB burden due to HIV. PMID- 22037067 TI - Pregnant Nigerian women's view of cesarean section. AB - OBJECTIVE: Cesarean section (C/S) is still being perceived as an abnormal means of delivery by many antenatal women in Nigeria. This study aims to determine the perceptions of antenatal clients in the southeastern Nigeria on C/S. MATERIALS AND METHODS: The study was conducted using a structured questionnaire administered to 300 consenting pregnant clients attending the antenatal clinic. The data were analyzed and presented in a simple frequency table. RESULTS: The average C/S rate in the hospital was 16.6%. Only 4 (1.4%) viewed C/S as very good and elected to undergo C/S. Thirty-four (12.3%) considered C/S as bad and would reluctantly undergo the procedure. Two hundred and twenty-five (81.2%) would accept C/S if their life or that of their fetus is in great danger. CONCLUSION: This study affirms previous suspicion that a significant proportion of antenatal clients are averse to C/S and the negative cultural perception of the people to C/S reinforced this aversion. PMID- 22037068 TI - Retrobulbar versus subconjunctival anesthesia for cataract surgery. AB - OBJECTIVES: To compare the effectiveness, in terms of pain relief and akinesia of retrobulbar and subconjunctival an aesthesia during cataract surgery and also to compare the degree of postoperative ptosis associated with each technique. MATERIALS AND METHODS: Consecutive adult patients undergoing cataract surgery between March and June 2008 at the Guinness Eye Center Onitsha, were randomized into retrobulbar and subconjunctival an aesthesia by simple random sampling. Patients' subjective perception of pain was graded into none, mild, moderate and severe; eyeball movement during surgery was graded into none, slight, moderate excessive. Two weeks after surgery, the palpebral fissure width was measured with the metre rule to determine the degree of post-operative ptosis. RESULTS: Of the 90 patients studied, 55 (61.1%) patients had subconjunctival an anesthesia while 35(38.9%) had retrobulbar injection. In the retrobulbar injection group 25 (71.4%) patients had none or mild pains compared to 44 (80.0%) in the subconjunctival injection group; while 10 (28.6%) patients in the retrobulbar group experienced moderate to severe pains, 11 (20%) patients in the subconjunctival group had moderate pains and none experienced severe pains. But the difference in the degree of pain perception between the 2 groups is not statistically significant (chi2 = 0.01; df - 1; P>0.05 ). In the retrobulbar injection group, there was none or slight movement of the globe in 30 (85.7%) patients compared to 49 (89.1%) patients in the subconjunctival group. While 5 (14.3%) patients in the retrobulbar injection group had moderate globe movement, no patient in this group had excessive movement. In the subconjunctival injection group, 5 (9.1%) patients had moderate movement and 1 (1.8%) patient had excessive eyeball movement. The difference in the movement of the eyeball between the retrobulbar and the subconjunctival injections group was not significant (chi2 = 0.004; df - 1; P>0.05 ). In the retrobulbar injection group, the palpebral fissure width was within >= 10mm in 18 (51.0%) patients compared with 29 (53.0%) patients in the subconjunctival group. This difference was not statistically significant (chi2 = 0.0006; df - 1; P>0.05 ). CONCLUSIONS: Both retrobulbar and subconjunctival an aesthetic techniques are effective and safe for cataract surgery although the pain experience may be slightly more for patients being operated upon under retrobulbar anaesthesia. PMID- 22037069 TI - The lumbosacral radiographs in the initial screening of low back pain - is one view enough? AB - BACKGROUND: Radiological imaging is mandatory, when investigating patients with low back pain (LBP). A minimum of three plain radiographic views of lumbosacral spine are routinely requested for by the attending clinicians. OBJECTIVE: This study is therefore carried out to determine if only one view will be sufficient in the initial screening of patients with low back pain. MATERIALS AND METHODS: The antero-posterior (AP) and lateral plain radiographs of patients referred to the radiology department on account of low back pains in an eighteen month period (June 2007 to November 2008) were reported by two certified radiologists. The findings were subjected to statistical analysis. The Kappa agreement for the two independent reports was between 0.602 and 0.908. RESULTS: The radiographs for 638 patients were reviewed. 365 (57.2%) were females and 273 (42.8%) were males. The age ranged from 20 years to 85 years with a mean of 56.4 years. Within the age group of 20-69 years, females were found to significantly present earlier than men with LBP (P< 0.041). The AP view had a significantly higher rate of reported normal findings that the lateral view (P<0.000). Osteophytic outgrowth was the commonest finding in both views although the rate of detection was higher on the lateral view, as with the other abnormal findings. CONCLUSION: This study shows that the lateral radiographs show significantly more findings than AP on plain radiographs. It is therefore recommended that lateral radiograph is adequate in the initial screening of patients with low back pain. PMID- 22037070 TI - Prevalence of dermatological lesions in hospitalized children at the University College Hospital, Ibadan, Nigeria. AB - OBJECTIVE: Skin disorders constitute a significant proportion of consultations in children's clinics; however, there is a paucity of data on the prevalence of dermatological lesions in hospitalized children in Nigeria. This study determines the prevalence of dermatological lesions in hospitalized children. MATERIALS AND METHODS: In this cross-sectional study, 402 children aged three months to twelve years admitted in the Pediatric wards of the University College Hospital, Ibadan, were enrolled over a six-month period. Examination of the skin and its appendages was done for each patient. Data on the socioeconomic status, hygiene, and health related factors were also obtained using a structured questionnaire. RESULTS: Over 96% of the children had at least one identifiable skin lesion. The five leading skin lesions were post-inflammatory hyperpigmentation (49.5%), BCG scar (28.4%), Mongolian spots (27.1%), junctional melanocytic nevi (20.1%), and cafiota-au-lait macules (18.4%). The leading infectious skin disease was pyoderma (13.4%), followed by tinea capitis (6.7%). Scarification marks (P=0.001), tinea capitis (P=0.014), plantar fissuring (P=0.001), and impetigo (P=0.016) were associated with low socioeconomic classes, while the presence of BCG scar (50.0%) was associated with the high socioeconomic class. CONCLUSIONS: This study shows that dermatologic lesions are common in hospitalized children. Identifying them will provide an opportunity for pediatricians to educate parents on the various causes as well as prevention of lesions. PMID- 22037071 TI - Periapical granuloma associated with extracted teeth. AB - OBJECTIVE: This article aims to determine the incidence of periapical granuloma from extracted teeth and correlate the clinical diagnoses with the histopathological types of periapical granuloma. PATIENTS AND METHODS: Over a period of eight months, a prospective study designed as a routine biopsy of recoverable periapical tissues obtained from patients who had single tooth extraction was carried out. RESULTS: One hundred and thirty-six patients participated in the study, with 75 (55.1%) histopathologically diagnosed periradicular lesions. There were 23 (16.9%) cases of periapical granuloma, with a male to female ratio of 2: 1. The lesion presented mostly between the third and fourth decades of life (n=9, 6.6%). Clinically diagnosed acute apical periodontitis was significantly associated with periapical granuloma, with predominantly foamy macrophages and lymphocytes (P<0.05). CONCLUSION: Periapical granuloma appears to be a less common periapical lesion in this study compared to the previous reports. In contrast to reports that relate to an acute flare of the lesion with abundant neutrophilic infiltration, this study has shown marked foamy macrophages and lymphocytes at the acute phase, which are significantly associated with the clinical diagnosis of acute apical periodontitis. We recommend the classification of periapical granuloma into early, intermediate, and late stages of the lesion, based on the associated inflammatory cells. PMID- 22037072 TI - Extrapulmonary tuberculosis: fine needle aspiration cytology diagnosis. AB - BACKGROUND: The increasing prevalence of extrapulmonary manifestation of tuberculosis with the HIV scourge is a cause for concern. OBJECTIVE: To determine the role of fine needle aspiration cytology (FNAC) in the diagnosis of extrapulmonary tuberculosis. PATIENTS AND METHODS: This is a consecutive 9-year analysis of patients with peripheral lymphadenopathy. All the patients had fine needle aspiration. Smears were made, fixed in 95% alcohol and stained with hematoxylin and eosin and Zeihl Neelsen stains. RESULTS: 48 patients, 31 males and 17 females, were analyzed. The mean age was 27.9 years. Aspirates were mainly from cervical lymph nodes. Four patients were HIV 1 seropositive. Macroscopically, 23 (48%) of the aspirates were purulent and 7 (14.6%) had caseous material. Microscopy showed granular eosinophilic material (caseation), multinucleated giant cells, epithelioid cells, neutrophils and lymphocytes. Staining for acid-fast bacilli was positive in 23 (48%) cases. CONCLUSION: Early diagnosis of extrapulmonary tuberculosis in a resource-limited setting can be achieved with fine needle aspiration cytology technique (FNAC). This will ensure prompt treatment and thus reduce attendant morbidity and mortality. PMID- 22037073 TI - Prevalence of hypertension amongst persons with diabetes mellitus in Benin City, Nigeria. AB - OBJECTIVE: To determine the prevalence of hypertension amongst persons with diabetes mellitus (DM) in Benin city. MATERIALS AND METHODS: Four hundred and fifty diabetic subjects were evaluated for hypertension by measuring their blood pressure using a sphygmomanometer at the diabetes clinics of the University of Benin Teaching Hospital and Central Hospital, both in Benin City, Nigeria. Other data obtained included age, sex, type of DM, weight, height, body mass index and waist hip ratio. RESULTS: Two hundred and forty-four out of 450 subjects had hypertension, thus giving a prevalence rate of 54.2%. 124 males (50.8%) were hypertensive compared with 120 (49.2%) females, but this difference was not significant (chi2 = 0.1, df = 1, P > 0.05). Thirteen (22.4%) of the 58 Type 1 subjects had hypertension, while 231 (58.9%) of the Type 2 subjects had hypertension, and this difference was statistically significant (chi2 = 27, df = 1, P < 0.05). CONCLUSIONS: Hypertension is prevalent in persons with DM. Studies have shown that adequate control of the blood pressure reduces the microvascular and macrovascular complications of DM. DM care providers must prescribe appropriate antihypertensive therapy to control hypertension in persons with DM. PMID- 22037074 TI - Knowledge and behavior towards voluntary blood donation among students of a tertiary institution in Nigeria. AB - BACKGROUND: Blood donation is the only way of acquiring blood to meet emergency requirements in cases of road traffic accidents, complications of pregnancy and childbirth, various anemic disorders and surgical emergencies among others. Globally, 80 million units of blood are donated each year, but only two million units are donated in sub-Saharan Africa where the need is enormous. The objective of this study was to determine the behavior of the students of a tertiary institution in Nigeria towards voluntary blood donation. MATERIALS AND METHODS: This is a descriptive cross-sectional study, which involved students of a tertiary institution in Nigeria. A multistage sampling technique was employed in selecting the participants for this study. A semi-structured self-administered questionnaire was used to collect information on socio-demographic characteristics, knowledge, attitude and factors affecting voluntary blood donation. The data obtained were analyzed using EPI-INFO 2005 software Version 3.3.2. RESULTS: Less than two-thirds (61%) of total respondents had good knowledge of blood donation. More than three quarters (85%) of the respondents had never donated blood. Of the 15% that had donated, only 3% donated voluntarily. Among those that had ever donated, males (57%) were more than females. Many of the donors donated for relatives (57%). The majority of the respondents were compelled to donate because of emergency situations (75%). The reasons why many did not donate were lack of opportunity (45%) due to tight lecture schedule and inadequate knowledge (24%). Gift items such as hematinics, T shirts and wrist bands (29%) would motivate respondents to donate. CONCLUSION: The Students' Union body and other Organizations in the University should include a blood donation drive in their monthly/annual activities. The University authorities, the University health service centre and the Hematology Department of the Teaching hospital should collaborate in promoting voluntary blood donation among the students. PMID- 22037075 TI - The state of occupational radiation protection and monitoring in public and private X-ray facilities in Edo state, Nigeria. AB - AIMS AND OBJECTIVES: To find out the state of radiation protection and monitoring practices of the public and private X-ray centres in Edo state. MATERIALS AND METHODS: Survey visits were made to all the functional X-ray facilities in Edo state and the available facilities identified, staff interviewed and collected data analyzed. RESULT: There are 18 functional X-ray facilities comprising 10 (55.56%) publicly owned and eight (44.44%) privately owned. Only two (20%) of the public and five (62.5%) of the private X-ray units have personnel and environmental monitoring. All the X-ray centers in both public and private hospitals have effective lead aprons. All the public (100%) and only four (50%) of the private centers have gonadal shield although none is using them on a routine basis. Qualified radiographers are available only in five (50%) of the public and six (75%) of the private centers. Only three (30%) of the public X-ray centers have the services of radiologists. Among the private X-ray units, five (62.5%) have radiologist while three (37.5%) have no radiologist. Only one (10%) of the public centers and one (12.5%) private X-ray centre have a purpose-built adequately designed X-ray unit with barium plasters and lead lining of walls and doors. There is also only limited lead lining of doors and walls in three (37.5%) private units while no lead lining or barium plasters are used in five (62.5%) of the private units. No X-ray unit in Edo state uses digital radiography or computerized information system. This means that lost hard copy must be repeated, leading to more radiation to patients and staff. CONCLUSIONS: There are inadequate radiation protection and monitoring practices in most of the functional X-ray facilities in Edo state with only five (62.5%) of the private and two (20%) of the public X-ray units monitored. There is poor adherence to the advice of the medical physicists due to the cost implications of the implementation. PMID- 22037076 TI - Contents and readability of currently used surgical/procedure informed consent forms in Nigerian tertiary health institutions. AB - BACKGROUND: Surgical informed consent forms should have evidence that their use will enhance a shared decision-making which is the fundamental objective of informed consent in clinical practice. In the absence of any guideline in Nigeria on the content and language of informed consent forms, we sort to examine the surgical and procedure consent forms used by Federal tertiary health institutions in Nigeria, to know whether they fulfill the basic elements of informed consent. MATERIALS AND METHODS: The surgical and procedure informed consent forms of 33 tertiary health institutions in Nigeria were assessed for their readability and contents. Adequacy of their content was evaluated based on provision for 28 content items identified as necessary information to be provided in a good consent form. The potential of the forms to be comprehended were assessed with Flesch readability formula. RESULTS: The contents of majority of the forms were scant. None of the forms made provision for documentation of the patient's permission for blood transfusion, tissue disposal, awareness of the risks of not undergoing the prescribed treatment, and the risk of anesthesia. Risk disclosures were only mentioned in specific terms in 11.4% of the forms. Less than 10% of the forms made provisions for an interpreter, signature of anesthetists, alternative to the procedure to be mentioned, and answering of the patient's questions. The Flesch reading ease scores of the forms ranged from 34.1 (Difficult) to 67.5 (Standard), with a mean score of 55.2 (Fairly difficult level). Field evaluation of the forms show that they shall be partly understood by 13- to 15-year-old patients with basic education but are best understood by literate adult patients. CONCLUSION: The content of majority of the informed consent forms used in Nigerian tertiary health institutions are poor and their readability scores are not better than those used in developed parts of the world. Health Institutions in Nigeria should revise their informed consent forms to improve their contents and do a usability trial on the sample forms before deployment in order to ensure that they are comprehensible for their patient population. PMID- 22037077 TI - Millennium development goals-knowledge and attainability as perceived by doctors: a case study. AB - OBJECTIVE: To audit the knowledge of doctors and evaluate their disposition toward the attainment of the Millennium Development Goals (MDGs). MATERIALS AND METHODS: Semi-structured questionnaires requesting information about knowledge of the acronym "MDGs" were administered on willing doctors at three tertiary health centers: University of Ilorin Teaching Hospital, Federal Medical Centre, Bida, and Federal Medical Centre, Yola. Data were analyzed using frequency tables and simple statistical methods. RESULTS: One hundred and eighty-three doctors participated in the study, comprising 65 (35.5%) from Bida, 18 (9.8%) from Yola, and 100 (54.7%) from Ilorin, with a male to female ratio of 2:1 (P < 0.05). Thirty-nine respondents (21.3%) had no fore kowledge of MDG (P < 0.05). Only 77 (42.1%) of the respondents who had fore knowledge of "MDG" knew the number of goals to be eight (P < 0.05). Among those who had fore knowledge of MDG, only 34 comprising 15 (10.4%, Bida), 1 (0.7%, Yola), and 18 (12.5%, Ilorin) could correctly list a minimum of four of the MDGs (P < 0.05). Only 12 (8.3%) of the respondents believed that the MDGs are very achievable. CONCLUSION: There is an absolute need for more elaborate publicity on the MDGs among doctors as they are key players if attaining the MDGs is to be a reality. PMID- 22037078 TI - Fetal macrosomia: obstetric outcome of 311 cases in UNTH, Enugu, Nigeria. AB - BACKGROUND: In modern obstetrics, fetal macrosomia is a major contributor to obstetric morbidity. It is an important cause of perinatal morbidity and mortality. AIM: This study aims to determine the maternal characteristics, fetal and neonatal complications associated with fetal macrosomia, and its contribution to obstetric morbidity in Enugu, Nigeria. MATERIALS AND METHODS: This was a 3 year retrospective study carried out from 1 st January 2005 to 31 st December 2007. RESULTS: There were a total of 434 cases of fetal macrosomia out of 5,365 deliveries. The incidence of fetal macrosomia was 8.1%. Only 311 case notes (71.6%) were available for analysis. Statistical analysis showed that mothers of macrosomic newborns were older (30.6 +/- 5.6 vs. 27.4 +/- 4.74; P = 0.001), higher parity (4.1 +/- 2.7 vs. 2.5 +/- 1.07; P = 0.001), and weighed more at term (89.13 +/- 6.17 kg vs. 71.43 +/- 5.27 kg; P = 0.002). The study group had more mothers with previous history of macrosomic babies (39.5% vs. 12.5%), diabetes (3.2% vs. 1%), significant higher cesarian section rate (27.3% vs. 11.9%, P = 0.001), and operative vaginal delivery (3.6% vs. 1%; P = 0.001) compared with the control. There was male dominance in the study group compared with the control (63% vs. 56.3%; P = 0.001), higher risk of fetal asphyxia (P = 0.001), and greater mean birth weight (3.6 +/- 1.2 kg vs. 3.2 +/- 0.6 kg; P = 0.002). There were 7 (2.3%) cases of shoulder dystocia in the macrosomic group and none in the non-macrosomic group. The stillbirth rate (3.2/1000) was the same in both study group and control. This was not statistically significant (P = 0.124). CONCLUSION: The precise determination of fetal weight is only done at delivery. Clinical and ultrasound determination of fetal weight are highly imprecise especially at the third trimester. The route of delivery should therefore be individualized. PMID- 22037079 TI - Age-related macular degeneration in Onitsha, Nigeria. AB - OBJECTIVES: To determine the incidence, pattern and ocular morbidity associated with age-related macular degeneration (AMD) at the Guinness Eye Center Onitsha Nigeria. MATERIALS AND METHODS: The case files of all new patients aged 50 years and above seen between January 1997 and December 2004 were reviewed. The files of patients with AMD were further studied. Information on age, gender, occupation, duration of symptoms, type of maculopathy, visual acuity, ocular and systemic co morbidities were abstracted into a standard proforma and analyzed using the chi square test, student t-test and confidence interval estimation. RESULTS: Two hundred and fifty-six of 7966 (3.2%) new patients had AMD; M:F = 2:3; 60 -79 year age group constitute 70% of the cases. Non-neovascular AMD occurred in 210 (82%) patients with 182 (71.1%) having early AMD and 28 (10.9%) geographic atrophy. Neovascular AMD occurred in 46 (18%) patients. AMD was bilateral in 221 (86.3%) patients. Most patients presented late. Systemic co-morbidities were hypertension and diabetes; the main ocular co-morbidities were cataract and glaucoma. Thirty four (13.3%) patients were bilaterally blind and 130 (50.8%) had bilateral visual impairment. Of the blind patients 13(38.3%) had neovascular AMD and 6 (17.7%) had geographic atrophy. This makes AMD the cause of blindness in 7.4% of the patients. An affected eye was more likely to have low vision than an unaffected eye (95%CI: 0.07, 0.21; P<0.05); persons aged 70 years and above were more likely to be blind (chi2 - 7.26, df -1; P<0.05); females were also more likely to be blind than males (t - 2.857, df - 8; P<0.05) and neovascular AMD significantly causes more blindness than the non-neovascular type (95% CI: 0.11, 0.37; P<0.05). CONCLUSIONS: AMD was the main cause of blindness in 7.4% of the patients. Treatment facilities including low vision aids for AMD patients should be provided in eye hospitals in Nigeria. Health education of the public highlighting the risk factors for AMD should be mounted as part of Vision 2020 programme in Nigeria. A community based study is required to fully define the epidemiologic characteristics of AMD in Nigerians. PMID- 22037080 TI - Immunohistochemical detection of Her-2/neu overexpression in breast carcinoma in Nigerians: a 5-year retrospective study. AB - OBJECTIVE: To determine the pattern of Her-2/neu status among breast carcinoma in the University of Benin Teaching Hospital, Benin City, Nigeria. MATERIALS AND METHODS: Immunohistochemical staining for Her-2/neu was performed on 10% formalin fixed, paraffin-embedded primary carcinoma of the breast from 83 patients, between 2003 and 2007 using anti-Her-2/neu rabbit polyclonal antibody (DakoCytomation, CA, USA) and reactivity detected by an avidin-biotin immunoperoxidase method. The clinicopathologic parameters analyzed were patients' age, histological types, and tumor grade. The Her-2/neu Dako scoring system was used. RESULTS: During the 5-year period, 83 histologically confirmed cases of invasive breast carcinoma were assessed for Her-2/neu status. These included 67 (80.7%) cases of invasive ductal carcinoma, nine cases of invasive lobular carcinoma (10.8%), three cases of medullary carcinoma (3.6%), two cases of papillary carcinoma (2.4%), and a case each of mucinous and clear cell carcinoma (1.2%). Mean age of patients was 48.9 +/- 13.6 years with an age range of 25 to 83 years. Only nine (10.8%) cases showed immunopositivity for Her-2/neu. Seven of these were cases of invasive ductal carcinoma, while two were invasive lobular carcinoma. Tumors were predominantly high grade with grade III, II, and I accounting for 42, 28, and 13 cases, respectively. There was no significant correlation between patient age, the various histological types, tumor grade, and Her-2/neu positivity. CONCLUSIONS: This study indicates that Her-2/neu may not be useful in defining the prognosis of breast cancer in this environment. Nevertheless, it highlights the need for routine immunostaining for Her-2/neu before institution of trastuzumab (Herceptin) therapy. PMID- 22037081 TI - Knowledge of HIV/AIDS among secondary school adolescents in Osun state, Nigeria. AB - BACKGROUND AND OBJECTIVES: This study aimed to assess the knowledge of secondary school pupils in Osun state about HIV/AIDS and the sources of their information. MATERIALS AND METHODS: A multistage random sampling technique was used to select 592 secondary school pupils from 5 local government areas of Osun state, Nigeria. A self-administered questionnaire was used which composed of questions on their knowledge and sources of information about HIV/AIDS. RESULTS: About half believed that HIV can be contracted via mosquito bites and 53.7% believed via kissing. Half of the respondents agreed that a person who looks healthy can be infected and possess the ability to describe the look of an infected person. Majority (92.6%) claimed to have heard about HIV/AIDS prior to the study. More than half (67.8%) agreed that HIV/AIDS is a life-threatening disease, 29.4% said there is a cure for AIDS, and 77.6% thought that the government is doing enough to deal with the disease. The most important sources of HIV/AIDS information among the respondents were the media and the least important sources of information were the traditional healers (35.3%). CONCLUSION: This study revealed a high-level misconception among secondary school pupils in Osun state, Nigeria. Mass media was the major source of information with doubtful effectiveness evidenced by obvious erroneous beliefs. An improved multisectorial approach in HIV/AIDS education with greater participation of school and public libraries is advised. PMID- 22037082 TI - Outcome of twin deliveries at the University of Maiduguri Teaching Hospital: a 5 year review. AB - OBJECTIVES: The objectives of the study were to determine the outcome of twin births at the University of Maiduguri Teaching Hospital (UMTH), Maiduguri, in terms of morbidity and mortality and to recommend possible measures to curtail or reduce some of the preventable complications. MATERIALS AND METHODS: This is a 5 year retrospective study, from January 2000 to December 2004, of twin births at the UMTH. RESULTS: There were 196 twin deliveries in 8431 total deliveries, with a twin incidence of 2.3%. Dizygotic twins accounted for 63.4%. The increasing maternal age and positive family history of multiple pregnancies were associated with the increasing twinning rate. The main complications encountered were preterm labor, pregnancy-induced hypertension, and cord prolapse. The perinatal mortality rate of 107.5/1000 births was higher than that observed for singleton pregnancies in the same institution. Similarly, there was a higher Cesarian section rate of 24.7% compared to singletons within the same period. There were significantly higher perinatal mortality rates among the preterm (P = 0.000002) and low-birth-weight (P = 0.000004) fetuses. CONCLUSION: Considering that fetal prematurity and low birth weight, sequelae to preterm labor, are the commonest causes of perinatal death in this study, efforts should be geared during the antenatal period toward the prevention of a premature birth. PMID- 22037083 TI - Prevalence of oral mucosal lesions from birth to two years. AB - OBJECTIVE: The purpose of this study was to determine the prevalence of lesions of the oral mucosa from birth to two years in Turkish pediatric patients . MATERIALS AND METHODS: A total of 299 infants from newborn to two years of age were evaluated from the Outpatient Clinics of the Pediatric Department, in the Fatih University Hospital, Ankara, Turkey. The mucosal lesions were documented. The data were presented as percentages and for categorical comparisons Chi-square or Fisher's Exact test were used. A P-value less than 0.05 was considered statistically significant. RESULTS: Of the 299 infants, mucosal lesions were seen in only 65 (21.27%). In the study, the most common lesions were candidiasis (10.70%), Ebstein's pearls (2.68%), and geographic tongue (2.68%). The frequency of children with mucosal alterations was higher in the group of children from two to twelve months. CONCLUSIONS: Although the lesions that were found the most in our study were benign lesions, unrelated to systemic diseases, we still believe that oral mucosal lesions can be a sign of a systemic or dermatological disease in infants, which affects the oral feeding of the infants. Routine examination of the oral mucosa should be a part of the pediatric examination. PMID- 22037084 TI - Pattern and determinants of blood transfusion in a Nigerian neonatal unit. AB - OBJECTIVE: To determine the pattern and determinants of blood transfusion in a Nigerian neonatal unit. MATERIALS AND METHODS: Newborn babies who required blood transfusions between January and December, 2008, were studied. The sex, age, and weight at the first transfusion, clinical conditions, indications for transfusion, and the outcome were analyzed with bivariate and multivariate methods. RESULTS: A total of 402 neonates were hospitalized and 112 (27.9%) had blood transfusion; 61.9% had exchange transfusion, 66.1% had red cell transfusion, and 8% had plasma transfusion. There were 251 transfusions with a rate of 4.8 transfusions per week. Blood transfusions were done for severe jaundice (55.4%), severe anemia (40.2%), and bleeding disorders (4.4%). Weight < 2.5 kg, outside delivery, and jaundice were independent determinants of neonatal transfusion. CONCLUSION: The blood transfusion rate in this facility was remarkably high. Improved standard of newborn care and infrastructural support are required to reduce the transfusion rate. PMID- 22037085 TI - Prognosis and outcome of acute stroke in the University College Hospital Ibadan, Nigeria. AB - BACKGROUND: Many factors influence the outcome of acute stroke, the third leading cause of morbidity and mortality globally. OBJECTIVE: To identify the determinants of outcome of acute stroke. MATERIALS AND METHODS: A prospectively study of 66 adult patients who presented to the medical emergency unit of University College Hospital (U.C.H), Ibadan, in coma from acute stroke, from August 2004 to March 2005, was undertaken after obtaining ethical clearance and written consent of the patients' relations. RESULT: Acute stroke constituted 33% of medical coma, 3.2% of hospital emergencies, 1.0% of total hospital admissions, and 7.3% of medical deaths during the study period. The stroke subtypes were intracerebral hemorrhage (78.8%) and large cerebral infarction (21.2%) with respective case fatalities of 69.7% and 13.6% at 4 weeks. Males constituted 75.8% of the patient population with sex-specific mortality of 68.2%. The highest age specific mortality of 65.2% was in the 40-59 years group. The common risk factors were systemic hypertension, obesity, alcohol/substance abuse, and diabetes mellitus. Co-morbidities included aspiration pneumonia, recurrent seizures, hyperglycemia, and sepsis. CONCLUSION: Age above 39 years, male gender, systemic hypertension, early onset of coma after stroke, and presence of co-morbidities were associated with poor stroke outcome. PMID- 22037086 TI - A histopathological study of carcinoma of the prostate in Port Harcourt, Nigeria. AB - OBJECTIVES: To determine the incidence of prostate cancer in Port Harcourt and the surrounding towns whose residents patronize the University of Port Harcourt Teaching Hospital for tertiary health care, histologically characterize the patterns of these cancers, and grade them according to the Gleason scheme. MATERIALS AND METHODS: Blocks and slides of prostate specimens received at the Department of Anatomical Pathology, University of Port Harcourt Teaching Hospital between January 1997 and December 2006 were retrospectively selected for this study. The slides were studied using a binocular Olympus light microscope. Patients' age at presentation, presenting symptoms, and clinical diagnosis were sorted out from the request cards and the department's archival register. RESULTS: Carcinoma was diagnosed in 198 specimens (37.4%) of the 529 cases reviewed. Of these, 164 (82.8%) were clinical carcinoma (having been found in clinically suspected carcinoma cases for which trucut biopsies were undertaken), while 34 (17.2%) were incidental carcinoma cases (being found in prostatectomy biopsy cases of patients clinically diagnosed with nodular hyperplasia). All of the clinical carcinomas were adenocarcinomas predominantly moderately differentiated and of large acinar pattern. Also, all of the incidental carcinomas were adenocarcinomas predominantly well differentiated and of large acinar pattern. The Gleason scores (GSs) were varied but predominantly of high values, particularly with clinical carcinoma cases. The age range was 42 to 90 years and the mean was 70 years with a peak of 70 to 79 years. CONCLUSION: The incidence of prostate cancer in Port Harcourt is high relative to other Nigerian centers where similar studies have been carried out and compares well with the high incidence found among African American men. Histologically, all cases are acinar adenocarcinomas. Most patients present late with high GS carcinoma and therefore have poor prognosis. There is a need for enlightenment of the male populace on the high incidence of this deadly disease as well as for screening to reduce the number of patients presenting late and therefore improve prognosis. PMID- 22037087 TI - Caring for patients with brain tumor: the patient and care giver perspectives. AB - BACKGROUND: Patients with brain tumors form a heterogeneous group in terms of clinical presentation and pathology. However, the impact of the disease on patients' families is often more homogenous and frequently quite profound. A considerable body of literature is available on the management of brain tumors and recently, the National Institute for Clinical Excellence has developed guidelines on the care of brain tumor patients that should improve the overall outcome for the patient from both the disease and psychological aspects. OBJECTIVES: An increasing number of studies have attempted to address the impact of the disease on the care givers and relatives of these patients, but few have considered the problem simultaneously from both the patient's and care giver's perspective. In this study, we analyzed the psychosocial and general health of brain tumor patients and related this to the care givers. MATERIALS AND METHODS: This is a questionnaire-based postal survey of 168 patients and their relatives. We examined how the health and psychological well-being of the caregiver may affect the quality of care. RESULTS: There is significant physical, social, and psychosocial morbidity associated with caring for brain tumor patients. Patients worry about their care givers and this constitutes additional stress for the patient. CONCLUSIONS: No constructive and lasting improvement can be made to the quality of life of patients with brain tumor until the health and welfare of their care givers are factored into the care package. With better service to the patient, it is hoped that the burden of care will lighten for the care givers. PMID- 22037088 TI - Oxyphil cell adenoma in a Nigerian: case report and review of the literature. AB - Oncocytomas of the lacrimal gland are rare tumors. We report the first documented case in Nigeria. This was an interventional case report. A complete ophthalmologic and systemic examination with available pertinent investigations was done, followed by a modified exentheration and histopathologic examination. A 60-year-old Nigerian housewife was evaluated for a slow-growing, right upper lid mass associated with visual lesion in the ipsilateral eye. Plain skull x-rays revealed a soft tissue in the right eye orbit without any bony extension. A modified exentheration was done. Histopathology showed sheets of oxyphil cells in the lacrimal gland. Although rare, more cases of oncocytomas may exist than are reported in the literature. PMID- 22037089 TI - Dysmenorrhea due to a rare mullerian anomaly. AB - Mullerian duct anomalies may produce reproductive failure like abortion and preterm birth, or obstetric problems like malpresentation, retained placenta, etc., or they may be asymptomatic. Unicornuate uterus with a noncommunicating functional rudimentary horn is a type of mullerian anomaly that results in obstruction to menstrual blood flow, leading to endometriosis and dysmenorrhea. Though the majority of cases of dysmenorrhea in adolescents are primary in nature and require only reassurance and symptomatic management, it is important to be aware of rare causes such as mullerian anomalies so that these cases can be properly managed. Hence, we present this case report, with interesting illustrations, so as to increase awareness regarding these anomalies. PMID- 22037090 TI - Success of nephron-sparing surgery in the treatment of localized renal cell carcinoma. AB - Advancement in imaging techniques has now made it possible for small renal tumors to be detected incidentally. This has led to the use of minimally invasive techniques for treatment of these cases. A 33-year-old woman was diagnosed to have a small renal mass after routine abdominal ultrasonography for epigastric discomfort. Computed tomography scan was used to characterize the mass, and an elective partial nephrectomy was successfully carried out. The procedure is safe, less morbid, and has good oncological outcome. PMID- 22037091 TI - Ultrafast tracking of sound location changes as revealed by human auditory evoked potentials. AB - The rapid discrimination of auditory location information enables grouping and selectively attending to specific sound sources. The typical indicator of auditory change detection is the mismatch negativity (MMN) occurring at a latency of about 100-250 ms. However, recent studies have revealed the existence of earlier markers of frequency deviance detection in the middle-latency response (MLR). Here, we measured the MLR and MMN to changes in sound location. Clicks were presented in either the left or right hemifields during oddball (rare 30 degrees -shifts in location), reversed oddball, and control (sounds occurring equiprobably from five locations) conditions. Clicks at deviant locations elicited an MMN and an enhanced Na component of the MLR peaking at 20 ms compared to clicks at standard or control locations. Whereas MMN was not significantly lateralized, the Na effect showed a contralateral dominance. These findings indicate that, also for sound location changes, early detection processes exist upstream of MMN. PMID- 22037092 TI - Clinical psychopharmacology of borderline personality disorder: an update on the available evidence in light of the Diagnostic and Statistical Manual of Mental Disorders - 5. AB - PURPOSE OF REVIEW: Clinical considerations for evidence-based treatment of borderline personality disorder (BPD) are outlined in the context of the best available evidence, discussed with reference to BPD traits currently identified in the upcoming Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5) revision. The DSM-5 will highlight refractory affective, interpersonal, and identity symptoms in BPD as potential treatment targets. In addition to providing a framework for clinical decision-making, future research strategies will also focus on neurotransmitter systems of greater relevance to understanding overall personality functioning. RECENT FINDINGS: Although only a few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, several meta-analyses and systematic reviews converge on the consensus effectiveness of lamotrigine, topiramate, valproate, aripiprazole, olanzapine, and omega-3 fatty acid supplementation. Stronger evidence exists for treating disinhibition and antagonism than negative affectivity, particularly interpersonal facets of such traits. In addition, basic research suggests a future role for modifying glutamatergic, opioid, and oxytocinergic neurotransmitter systems to treat BPD. SUMMARY: Clinicians should utilize omega 3, anticonvulsants, and atypical antipsychotic agents in treating specific DSM-5 BPD traits, notably disinhibition, antagonism, and some aspects of negative affectivity. Future research will focus on normalizing opioid and oxytocin dysregulation, as an adjunct to evidence-based psychotherapy, in an effort to improve interpersonal functioning. PMID- 22037093 TI - [Spontaneous visits to the emergency service and hepatology day hospital by patients with liver cirrhosis]. AB - INTRODUCTION: Because of the current overload of emergency services, new units, such as day units, have had to be created. Liver cirrhosis (LC) is a chronic disease with frequent decompensations requiring medical attention. The aim of this study was to compare differences between emergency consultations in a hepatology day hospital (HDH) and in an emergency service (ES) among patients with LC. METHODS AND MATERIAL: We performed an observational prospective study. All patients with LC attending the HDH or ES from September 2007 to August 2008 were asked to complete a questionnaire. Demographic, clinical, and radiological variables were collected. RESULTS: There were 743 consultations, of which 62% involved the HDH. The mean age was 65+/-12 years, and the male/female ratio was 2:3. The most frequent diagnosis in the ES was hepatic encephalopathy (26.2% ES versus 6% HDH, p<0.001) followed by upper gastrointestinal hemorrhage (17.7% ES versus 0.6% HDH, p<0.001), while the most frequent diagnosis in the HDH was ascites (66.2% HDH versus 22.7% ES, p<0.001). The tests performed were as follows: blood analysis: 95% ES versus 60% HDH (p<0.01); radiology: 71% ES versus 11% HDH (p<0.01) and paracentesis: 51% ES versus 74% HDH (p<0.01). The mean length of stay in the ES was 21.3+/-121.5 hours compared with 3.3+/-2.4 hours in the HDH (p<0.001). A total of 53% of patients attended in the ES were hospitalized compared with 12% of those attended in the HDH (p<0.05). CONCLUSION: Patients with LC preferentially attend the HDH, where fewer tests are performed and the length of stay is shorter. The care provided in the HDH is appropriate and efficient. PMID- 22037094 TI - The role of pharmacotherapy in the prevention and treatment of paediatric metabolic syndrome--Implications for long-term health: part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni. AB - The metabolic syndrome (MetS) is defined as a clustering of risk factors predisposing to the future development of cardiovascular disease and Type 2 diabetes mellitus (T2DM). Its clinical relevance, above and beyond recognition and treatment of each of the component parts, is still hotly debated--especially within paediatric medicine. Prevention and treatment strategies for adult MetS focus on weight management, as obesity and insulin resistance are known to be at the central axis of the definition, alongside pharmacotherapy of integrally linked conditions such as hypertension and dyslipidaemia. In children and adolescents, however, opportunities for pharmacotherapy are currently limited and interventions aimed at weight management remain the sole treatment paradigm in the majority of cases. This is primarily due to a lack of long-term data relating to the degree of cardiovascular disease and T2DM risk from paediatric MetS, as well as concerns relating to safety and side effect profiles of currently available pharmacotherapies in those who are still growing and developing. Coupled with continuing concern about the recently recognised adverse effects of past and proposed anti-obesity drugs, this indicates that a new era of pharmacotherapy for paediatric MetS is unlikely to be imminent. In fact, the overall paucity of effective current interventions for paediatric MetS is concerning, especially given the fact that approximately 25-33% of all obese paediatric patients likely harbour the condition. It is therefore essential at the present time to concentrate efforts on properly testing the safety and efficacy of currently available products in well-constructed randomised controlled trials in obese adolescents. However, not all obese children and adolescents appear equally at-risk of long-term, weight-related morbidity and a change in emphasis is possibly warranted--one that moves away from simple weight reduction for all and more to a model of reducing long-term risk of cardiovascular disease and T2DM in those at greatest metabolic risk. PMID- 22037095 TI - Time course of strength and echo intensity recovery after resistance exercise in women. AB - The purpose of this study was to evaluate the time course responses of strength, delayed-onset muscle soreness (DOMS), muscle thickness (MT), circumference (CIRC), and ultrasonography echo intensity (EI) after a traditional hypertrophic isoinertial resistance training session in young women. Ten (22.0 +/- 3.2 years) healthy, untrained volunteers participated in the study. The resistance exercise session consisted of 4 sets of 10 repetitions at 80% of 1 repetition maximum (1RM) of the dominant arm elbow flexors. Maximum isometric elbow flexion peak torque (PT) at 90 degrees , MT, and EI were recorded for both arms at baseline (PRE), immediately after exercise (0 hours) and at 24, 48, and 72 hours after exercise. Comparisons were made using a 2 * 5 mixed factor analysis of variance. There was a significant (p < 0.05) loss in PT and increase in MT at 0, 24, 48, and 72 hours. In contrast, EI increased only after 24, 48, and 72 hours, not at 0 hours. There were no significant changes in PT, DOMS, MT, and EI in the nondominant (control) arm after the exercise protocol. Our data suggest that after 4 sets of 80% of 1RM of unilateral elbow flexion resistance exercise, nonresistance trained women need >72 hours to fully recover muscle strength, MT, CIRC, and EI. Furthermore, the EI appears to be a sensitive and reliable method to assess MD. PMID- 22037096 TI - Effects of various warm-up devices and rest period lengths on batting velocity and acceleration of intercollegiate baseball players. AB - It is common among competitive baseball players to swing bats while in the batter's box in an attempt to improve their batting performance. Players use bats of different weights during this time, and only a few studies have evaluated the optimal bat weight to increase performance. Previous studies have not investigated the optimal rest period after a warm-up with bats of varying weights. Therefore, we tested the peak bat velocity of 16 National Collegiate Athletic Association Division II intercollegiate baseball players at 1, 2, 4, and 8 minutes, after warming up with bats of 5 different weights. Measured variables were peak bat velocity at peak acceleration (PVPA), peak bat velocity of the swing (PV), peak bat acceleration (PA), and time to reach peak acceleration (TPA) using a chronograph, which measured the batting velocity in real time every 10 milliseconds throughout the swing. A repeated measure analysis of variance was run to assess group, time, and group by time interactions. If any main effects were found, a Tukey post hoc was employed to locate differences. There were significant (p <= 0.05) time effects for PVPA, PV, and PA but not for TPA. The PVPA, PV, and PA all increased over time, peaking from 4 to 8 minutes. There were no significant differences in any of the variables among the 5 bat weights used in the warm-up (p > 0.05). However, there were significant differences in PVPA, PV, and PA after 2, 4, and 8 minutes of rest compared with the preexperimental warm-up and 1-minute post-warm-up. From a practical standpoint, batters should warm up early and quickly in the batter's box to maximize the amount of recovery time before they swing at the plate. In addition, batters may want to take their time getting ready at the plate or take some pitches while at-bat in an attempt to maximize performance. Alternatively, the data imply that pitchers should throw their fastest pitch near the beginning of the at-bat to correspond with the potentially slower bat speeds of the batter. PMID- 22037097 TI - Enhancing the examiner's resisting force improves the validity of manual muscle strength measurements: application to knee extensors and flexors. AB - The purposes of this study were to test whether an examiner's strength may affect the validity of the knee muscle strength measurements using a hand-held dynamometer (HHD) and whether enhancing the forces applied by an examiner using a resistance-enhanced dynamometer (RED) would improve measurement validity. Twenty five young male volunteers (mean [+/-SD] age: 22.5 +/- 1.7 years) without a history of injury to the test limb and 6 male and 6 female experienced examiners participated in this study. Maximum resisting forces of the knee flexors and extensors were measured using RED, HHD, and a dynamometer (Kin-Com). For all testing conditions, poor to moderate associations were found between the HHD and Kin-Com, whereas there was a good to excellent relationship between RED and Kin Com. The systematic variations between RED and Kin-Com were also smaller than those between HHD and Kin-Com. The force values measured by RED were very close to those measured by Kin-Com. An examiner's strength affects the validity of the measurements using HHD. Enhancing the forces applied by the examiner to the tested segment using RED appeared to improve the validity of muscle strength measurements. PMID- 22037099 TI - A survey for the evaluation of the training period of cardiology specialists in Turkey. AB - OBJECTIVE: To evaluate postgraduate training period, social life and problems of cardiology residents in Turkey by using a questionnaire form and to compare with the core curriculum of European Society of Cardiology for general cardiology. METHODS: Overall, 529 residents of cardiology ages in range of 24-35 years (mean age: 26.5+/-2.0 years, 81.4% male) participated as volunteers in this cross sectional survey study. An 86-item questionnaire form was used to evaluate the education process, capacity of knowledge and skill and social effectiveness level of participants. The questionnaire were composed both closed- and open-ended questions. The questionnaire form was filled in with the face-to-face communication method. The data of survey were compared with the core curriculum of European Society of Cardiology for general cardiology training period. Chi square or Fischer exact test was used for statistical analysis. RESULTS: The participants were working in various university hospitals (70.3%) and training research (state) hospitals in 31 different provinces in Turkey (40.8% in Marmara region). They visited 40+/-10 outpatients and 10+/-5 hospitalized pts daily in the clinics. The 3-5 residents worked at the clinic on night shifts and mostly (89%) 8 or more night shifts per month were held in their first training years. During first three-years of training 76% of residents have performed echocardiography, 40.8%-transesophageal echocardiography and 10% - intraoperative echocardiography. The 84.3% of them evaluated exercise tests, 76.4%-Holter electrocardiography and 53.3%-tilt-table tests. The rate of residents working in coronary angiography laboratories was 54.3%. The 53.7% of residents performed coronary angiography and 64%-only in the 4th year of their training. The number of coronary angiography performance was under expected when compared with European Society of Cardiology curriculum. The 18.5% of residents were participated as assistant researcher in an international multi-center study and only 10% had an article published in national journals (4.3% published in Science Citation Index). The 30.6% considered the cardiology training period in their centers to be insufficient, whereas 37.4% found it partially sufficient and 31.9% sufficient. Only 32.9% of participants could dedicate time for social activities. CONCLUSION: According to the referred core curriculum of ESC for general cardiology the training of cardiology residents in non-invasive applications is adequate however coronary angiography applications are slightly insufficient in Turkey. In addition, the number of publications per capita is quiet low. PMID- 22037100 TI - Diagnostic accuracy and clinical utility of echocardiographic indices for detecting left ventricular diastolic dysfunction in patients with coronary artery disease and normal ejection fraction. AB - OBJECTIVE: The aim of present study was to assess the clinical utility and diagnostic accuracy of diastolic dysfunction criteria that were recommended in current American Society of Echocardiography and European Association of Echocardiography recommendations for prediction of increased LVEDP (>16 mmHg) in patients with coronary artery disease and normal EF. METHODS: Forty-five consecutive patients (mean age=61.5+/-10.3 years) referred for cardiac catheterization were enrolled in this prospective study. All patients underwent transthoracic echocardiography and tissue Doppler imaging within 24 hours before cardiac catheterization. Patients were divided into 2 groups according to left ventricular end diastolic pressure (LVEDP) (LVEDP>16 mmHg, n=23; LVEDP<=16 mmHg, n=22). Receiver operating characteristics curve analyses were performed and sensitivity, specificity, positive predictive value and negative predictive value were calculated for indices to detect high LVEDP. RESULTS: Among the indices, left atrial volume index (LAVI) >=34 ml/m2 (sensitivity=60.0% and specificity=90.0%) and ratio of transmitral to septal annular velocities during early filling (septal E/e' ratio) >=15 (sensitivity=30.4% and specificity=95.5%) had more reasonable sensitivity and specificity. Receiver operating characteristics curve analysis revealed that best predictors of high LVEDP were septal E/e' [area under curve (AUC)=0.694, standard error (SE)=0.66, p=0.01] and LAVI (AUC=0.669, SE=0.63, p=0.045]. There were statistically significant correlations between LVEDP and septal E/e' (r=0.541, p=0.001) and LAVI (r=0.461, p=0.002). A proposed algorithm consisting LAVI >=34 ml/m2 and septal E/e' >8 could determine diastolic dysfunction with a 95.6% sensitivity and 54.5% specificity. CONCLUSION: Septal E/e' (>=15) and LAVI (>= 34 ml/m2) were the better predictors of the increased LVEDP than the other echocardiographic parameters. There were statistically significant moderate positive correlations of LVEDP with septal E/ e' and LAVI. Combination of LAVI and septal E/e' is useful to detect diastolic dysfunction. PMID- 22037101 TI - Implications of tilt-table induced faint time in patients with reflex syncope. AB - OBJECTIVE: The aim of this study was to determine whether patients who faint earlier in the course of a tilt table study represent a separate population with a poorer prognosis or different pathophysiology. We analyzed differences across patients with different syncopal times on the tilt-table study to answer this question. METHODS: This was a retrospective, approved, chart review. From our database of over 6000 patients, we identified 1222 patients with syncope. After excluding patients with orthostatic hypotension, postural tachycardia syndrome and diabetes, we were left with 131 patients with pure reflex syncope. We divided fainters into an early (<20 minutes) and late (>20 minutes) faint times. Along with the tilt table test all patients underwent heart rate response for deep breathing, Valsalva maneuver and quantitative sudomotor axon reflex tests. RESULTS: By 10 minutes in the tilt study, only 18% of subjects had fainted, 65% by 20 minutes, 92% by 30 minutes and 96% by 35 minutes. Age was evenly distributed across all syncopal times. Neither the 14 abnormal cardiac responses to deep breathing nor the 20 abnormal Valsalva maneuvers, nor the 28 abnormal axon reflex responses clustered with an early or late faint time. CONCLUSION: A 10-minute tilt will miss 82% of syncopal episodes, while a 30- minute tilt increases the yield 10-fold, missing only 8%. Patients with early faint times did not differ from patients with late fainting times with regard to age or autonomic test abnormalities. Timing of syncope during the tilt table test does not associated with more severe dysautonomia. A prospective study is needed to confirm these observations. PMID- 22037102 TI - Relationship of brain natriuretic peptide with metabolic syndrome parameters: an observational study. AB - OBJECTIVE: Metabolic syndrome (MS) was independently associated with increased risk of incident heart failure and coronary artery disease. In this study, we sought to identify whether there is an association between metabolic syndrome components and left ventricular diastolic functions and brain natriuretic peptide (BNP) levels. METHODS: This study is a cross-sectional, observational study. Two hundred consecutive patients with MS were selected to form the study population. Echocardiographic parameters and BNP were determined. Mann-Whitney U test and Kruskal-Wallis test were used to compare BNP levels in categorical variables. Spearman rank correlation analysis was used to investigate the correlation between BNP level and other numerical variables. Linear regression analysis was used to find the variables affecting the BNP level. RESULTS: BNP level was higher in females than males [11.14 (0.12-87) vs 7.49 (0.01-99) pg/dl, p=0.04]. None of the MS parameters affects the BNP level in MS patients. MS criteria number that the patient had was not related to BNP level. Sixty seven percent of patients had left ventricular (LV) diastolic dysfunction. BNP was independent from LV diastolic function. Multiple linear regression analysis demonstrated that having diabetes mellitus increases BNP level by 7.73 unit (beta=7.73, 95% CI - 2.321 - 13.149, p=0.006). CONCLUSION: None of the MS parameters affects the BNP level in MS patients. Diastolic dysfunction existence did not affect the BNP level of MS patients. There is an association between diabetes mellitus and BNP, independent of left ventricle diastolic functions. PMID- 22037103 TI - Relationship between heart-type fatty acid-binding protein levels and coronary artery disease in exercise stress testing: an observational study. AB - OBJECTIVE: Although, there has been great improvement on the diagnosis and early treatment of acute coronary syndromes, especially in terms of myocardial damage biochemical markers, we do not have a specific marker yet, for using the diagnosis of stable coronary artery disease (CAD). This study aimed to evaluate the relationship between CAD and the changes of heart-type fatty acid binding protein (H-FABP) levels before and after exercise stress testing (EST). METHODS: A total of 47 patients were enrolled in this observational study. Of 47 patients, 21 had normal coronary anatomy; the remaining 26 patients had coronary lesions over 70% in at least one major coronary artery. All patients performed EST. Along with this, H-FABP levels before EST and at peak exercise, 1st hour, 3rd hour (3h), were measured in all patients. Differences among the measurements were evaluated through the Friedman test and Wilcoxon test, and the Bonferroni correction was applied to determine which measurement caused the difference. RESULTS: Contrary to expectations, the means of the H-FABP values measured at particular intervals for each group tended to decline from the basal level to the 3h level. When the difference between the 3h measurement and the basal level was compared in each group, the decreasing was statistically significant in both groups (p<0.05). A statistically significant decrease at the 3h measurement compared to the basal level in the CAD group was more apparent than in the control group (2.790+/-2.569 ng/ml vs. 0.837+/-2.070 ng/ml, p=0.009). CONCLUSION: We found that H-FABP levels did not increase during EST and contrary to expectation, were inclined to decrease. We thought that decreasing H-FABP levels likely resulted from exercise-induced proteinuria. PMID- 22037104 TI - From whole blood to component therapy: the economic, supply/demand need for implementation of component therapy in sub-Saharan Africa. AB - Blood may be transfused as whole blood or as one of its components. Because patients seldom require all of the components of whole blood, it makes sense to transfuse only that portion needed by the patient for a specific condition or disease. This treatment, known as "blood component therapy", allows several patients to benefit from one unit of donated whole blood. Blood components include red blood cells, plasma, platelets, and cryoprecipitate. A considerable literature has accumulated over the past decade indicating that leukocytes present in allogeneic cellular blood components, intended for transfusion, are associated with adverse effects to the recipient. These include the development of febrile transfusion reactions, graft-versus-host disease, alloimmunization to leukocyte antigens, and the immunomodulatory effects that might influence the prognosis of patients with a malignancy. Moreover, it has become evident that such leukocytes may be the vector of infectious agents such as cytomegalovirus (CMV), Human T-Lymphotrophic Virus 1/11 (HTLV-I/II), and Epstein Barr (EBV) as well as other viruses. Effective stewardship of blood ensuring that several patients potentially benefit from components derived from one unit of donated whole blood is important for economic, supply/demand reasons and to protect the national inventory at times of national blood shortage. Blood safety in developing countries can be improved by more appropriate use of blood components rather than whole blood transfusion and the provision of alternatives such as oral and intravenous iron, erythropoietin, saline and colloids. This will facilitate the optimal use of the limited blood supply. Political will and open mindedness to innovative ways to improve supply, appropriateness, optimal use and safety of blood from all types of donors are essential to promote more evidence based approaches to blood transfusion practice in sub-Saharan Africa. PMID- 22037106 TI - In vitro and in vivo assessment of targeting lipid-based nanoparticles to the epidermal growth factor-receptor (EGFR) using a novel Heptameric ZEGFR domain. AB - Lipid-based oil-filled nanoparticles (NPs) with a high concentration of surface chelated nickel (Ni-NPs) were successfully prepared using a Brij 78-NTA-Ni conjugate synthesized with Brij 78 (Polyoxyethylene (20) stearyl ether) and nitrilotriacetic acid (NTA). The facile incorporation of the Brij 78-NTA-Ni conjugate into the NP formulation allowed up to 90% Ni incorporation, which was a significant improvement over the previously used standard agent DOGS-NTA-Ni which led to ~6% Ni incorporation. The Ni-NPs were targeted to the highly epidermal growth factor receptor (EGFR)-overexpressing epidermoid carcinoma cells A431. This was accomplished using a novel high affinity histidine*6-tagged EGFR-binding Z domain (heptameric Z(EGFR) domain). In vitro cell uptake studies showed enhanced internalization (up to 90%) of the targeted Ni-NPs in A431 cells with only <=10% internalization of the untargeted Ni-NPs. ICP-MS analysis used to quantify the amount of Ni in the cells were in close agreement with flow cytometry studies, which showed a dose dependent increase in the amount of Ni with the targeted Ni-NPs. Cell uptake competition studies showed that internalization of the targeted Ni-NPs within the cells was competed off with free heptameric Z(EGFR) domain at concentrations of 8.75ng/mL or higher. In vivo studies were carried out in nude mice bearing A431 tumors to determine the biodistribution and intracellular delivery. Near Infrared (NIR) optical imaging studies using Alexa750-labeled heptameric Z(EGFR) domain showed localization of 19% of the total detected fluorescence intensity in the tumor tissue, 28% in the liver and 42% in the kidneys 16h post i.v. injection. ICP-MS analysis showed almost a two-fold increase in the amount of intracellular Ni with the targeted Ni NPs. These new Ni-NPs could be a very useful tool for targeting and drug delivery to a wide range of EGFR positive cancers. PMID- 22037107 TI - Low melting point amphiphilic microspheres for delivery of bone morphogenetic protein-6 and transforming growth factor-beta3 in a hydrogel matrix. AB - Low melting-point poly(1,3-trimethylene carbonate-co-epsilon-caprolactone)-b poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate-co-epsilon-caprolactone), P(TMC-CL)(2)-PEG, was employed to fabricate microspheres for sustained growth factor delivery in a photocrosslinked N-methacrylate glycol chitosan hydrogel matrix. The P(TMC-CL)(2)-PEG had a melting range such that it was solid at 10 degrees C, yet liquid with a low degree of crystallinity at 37 degrees C. The in vitro degradation of P(TMC-CL)(2)-PEG microspheres was slow, regardless of the triblock copolymer molecular weight and so did not influence protein release. The size of protein loaded P(TMC-CL)(2)-PEG microspheres manufactured using a low temperature electrospray technique was between 65 and 85MUm. Initial formulation work was done with the model protein lysozyme, co-lyophilized with trehalose and encapsulated as approximately 2MUm particles within P(TMC-CL)(2)-PEG microspheres. This work indicated a sustained release could be achieved with high trehalose content (90% w/w) in the particles. Under these conditions, the release rate of bone morphogenetic protein-6 was more sustained than that of the excipient bovine serum albumin (BSA) and closely followed that of lysozyme. On the other hand, transforming growth factor-beta3 and the stabilizing agent BSA generated similar release profiles. This difference in release was proposed to be linked to the protein isoelectric point, with positively charged proteins possibly being more strongly adsorbed to the P(TMC-CL)(2)-PEG. Both growth factors were released in highly bioactive form, indicating the potential of the release approach. PMID- 22037112 TI - Association of a single nucleotide polymorphism in pregnancy-associated plasma protein-A2 with developmental dysplasia of the hip: a case-control study. AB - Developmental dysplasia of the hip (DDH), previously known as congenital hip dislocation, is a frequently disabling condition characterized by premature arthritis in later life. Genetic influence on DDH has been long known, but is still poorly understood. Previously, we have performed a genome-wide linkage scan with Affymetrix 10K genechip for a four-generation Chinese family, which included 19 healthy members and five patients with DDH. Parametric and nonparametric multipoint linkage analyses were carried out with Genespring GT v.2.0 software, and the logarithm of odds (LOD) score and nonparametric linkage (NPL) score were calculated. For parametric linkage analysis, an assuming autosomal recessive trait was used with full penetrance, and Affymetrix "Asian" allele frequencies. The NPL score of 2.698 (P=0.0156) and LOD score of 2.119 (theta=0) were obtained on chromosome 1q25.2a for one marker (rs726252). The single nucleotide polymorphism (SNP) rs726252 locates in the region of fifth intron of pregnancy associated plasma protein-A2 (PAPPA2). Although neither LOD nor NPL scores of rs726252 has exceeded 3.0, several researches have demonstrated that PAPPA2 have important consequences for the development of the fetus and normal postnatal growth. To further evaluate this possible association, in the present study, we examined the genetic association of rs726252 in PAPPA2 gene with sporadic DDH in Han Chinese population using case-control study, including 310 patients with sporadic DDH and 487 control subjects, and found a significant association between PAPPA2 and DDH. PMID- 22037113 TI - [Technical evaluation of nested PCR for the diagnosis of experimental sporotrichosis]. AB - BACKGROUND: Sporotrichosis caused by the dimorphic fungus Sporothrix schenckii can presents in a variety of clinical forms. Routine diagnosis is made by mycology and serology studies. Few investigations have been focused on the evaluation of the molecular diagnosis. AIM: To determine the value of the nested PCR technique for the diagnosis of experimental sporotrichosis in organs of mice, and to compare the results with the established laboratory diagnostic procedures. METHODS: BALB/c mice were inoculated with growing concentrations of the 2 morphological phases of the fungus. The infected animals were sacrificed one month later and specimens from liver, spleen, lung and testicle were obtained to perform wet mount, culture and molecular diagnosis by the nested PCR technique. Blood samples were obtained for determination of specific antibodies against S. schenckii by the double immunodiffusion procedure. RESULTS: The pathogenicity observed with the different concentrations of the fungus inoculated and its isolation by culture, showed scarce differences in the study of specimens from organs infected with the 2 morphological phases of S. schenckii. Specimens from organs of mice inoculated with the mycelial phase when studied by wet mount and culture, showed a higher positivity (100 and 37.5%) than those from mice inoculated with the yeast phase (73 and 2%). However, diagnosis by the nested PCR molecular technique applied to the latter specimens showed a higher percentage of positivity (75%) and 43% of positive results coming from animals infected with the mycelial phase. Specific antibody detection was positive in 100% all groups of infected mice. CONCLUSIONS: In the study of experimental sporotrichosis in mice, the culture, as well as the antibody detection, was an effective diagnostic procedure, while the nested PCR and microscopic studies had a lower diagnostic value. PMID- 22037114 TI - [Relevant aspects of the Hcp100 molecular marker of Histoplasma capsulatum and its potential therapeutic use in histoplasmosis]. AB - BACKGROUND: Fungal pathogens have developed strategies, involving genes expression that favors their persistence and multiplication in the host. The absence of molecules encoded by these genes could interfere with the growth and death of these fungi. In the past, a coactivator protein coding gene (Hcp100) of the fungus Histoplasma capsulatum was reported, which is overexpressed after 1h of contact between fungal yeast-cells and murine macrophages. The product of this gene, a protein of 100 kDa (Hcp100) of H. capsulatum, is probably a regulatory protein involved in the processes required for fungal adaptation and its survival in the intracellular hostile conditions of the macrophages. A 210-bp fragment of the Hcp100 marker has proved to be an excellent tool for H. capsulatum molecular detection in clinical samples. The potential use of this gene as a therapeutic target in Plasmodium falciparum has been explored through the inhibition of both, the gene and the protein p100 of the parasite, by blocking its growth. METHODS: Based on the above mentioned antecedents, we believe that the Hcp100 has an important role in the development and maintenance of the H. capsulatum yeast cells within macrophages. RESULTS AND CONCLUSIONS: To study the probable function of Hcp100 in the yeast-phase of this fungal pathogen is relevant to understand its activity and to propose it as a therapeutic target for histoplasmosis treatment. PMID- 22037115 TI - Early treatment in early undifferentiated arthritis. AB - The early diagnosis of new-onset rheumatoid arthritis (RA) has become a major objective for rheumatologists in order to identify a management strategy able to change the natural history of the disease and to prevent joint damage and functional impairment. Emergent evidence emphasizes the benefits of early aggressive therapy of RA. By the nineties, early arthritis cohorts have been collected throughout the world with the aim to increase the early referral of patients with early onset disease by the general practitioners and to collect data on the development of full-blown RA. The frequency of undifferentiated arthritis (UA) ranged from 23% to 81% in these early cohorts with most of them reporting a rate of 30%. The transition rate from UA to RA was between 13% and 54%. A percentage of 20-60% of patients with UA had a self-limiting disease. Our article deals with the controversy existing in the management of UA. Should every patient with UA be treated? Could patients with a favorable disease course be exposed to unnecessary risk with initiation of aggressive therapy with synthetic disease-modifying anti-rheumatic drugs (DMARDs) or biologic agents? The pros and cons of treating patients with UA are examined. PMID- 22037116 TI - Vaccination of patients with auto-immune inflammatory rheumatic diseases requires careful benefit-risk assessment. AB - Will vaccination raise the incidence of autoimmune diseases, what is the impact of increasingly crowded vaccination schedules, the vaccination in age groups and the risk of coincidental temporal association? All these issues are still under debate. However, for the time being, to avoid confusion in the medical community and the media, we have to adhere to guidelines established consensually by experts while ensuring a strict surveillance and reporting possible side effects. Recommendation for vaccination in patients with autoimmune inflammatory rheumatic diseases (AIIRD) based on the currently available evidence and expert opinion were recently formulated by an EULAR task force. Major recommendations for AIIRD include: i) vaccination should ideally be administered during stable disease; ii) influenza vaccination and pneumococcal vaccination should be strongly considered; iii) vaccination can be administered during the use of DMARDs and TNF-inhibitors, but before starting rituximab; iv) live attenuated vaccines should be avoided whenever possible in immunosuppressed patients; v) BCG vaccination is not recommended. PMID- 22037117 TI - To switch or not to switch after a poor response to a TNFalpha blocker? It is not only a matter of ACR20 OR ACR50. AB - The introduction in the therapeutic armamentarium of TNF inhibitors (TNFi) has greatly advanced the chance of obtaining a control of clinical manifestations and of structural damage progression in an important proportion of patients with rheumatoid arthritis (RA) Methotrexate (MTX)-poor responders. However not more than 50% of TNFi treated patients can reach relevant clinical benefits. Therefore the unmet medical question is: should we continue the therapeutic approach with a second or a third TNFi, or should we use other drugs, and change the mode of action of the second drug? These are practical issues that still do not have a definite answer. The real problem is that up to this moment no real biomarker is available to make the appropriate choice. The only clear-cut biomarker is represented by the positivity of rheumatoid factor (RF) or anti citrullinated peptide autoantibodies (ACPA). Seropositive patients seem to respond better than seronegative ones to B cell depletion therapy (Rituximab). This paper discusses the pros and cons of switching or swapping in RA patients poorly responder to the first TNFi. PMID- 22037118 TI - Toxicity of crude oil and pyrene to the embryos of beach spawning capelin (Mallotus villosus). AB - Due to a northward shift in oil and gas activities, there is an increasing need to understand the potential anthropogenic impacts of oil-related compounds on sub Arctic and Arctic organisms, particularly those in coastal habitats. Capelin (Mallotus villosus), a key fish species in the Barents Sea ecosystem, undertakes aggregated spawning at both intertidal and subtidal coastal localities in northern Norway. To investigate the sensitivity of capelin embryos to oil compounds, newly fertilized capelin eggs were collected from a spawning beach and exposed until hatch (32 days) to either the water soluble fraction of crude oil or the single PAH compound, pyrene. Threshold levels for egg mortality, development and hatching success were determined. Concentrations of 40 MUg/L crude oil (?26 PAHs) and 55 MUg/L pyrene significantly increased embryonic mortality rates and decreased hatching success, compared with controls, indicating that a potential oil spill in the vicinity of capelin spawning grounds may cause significant impacts. No significant incidence of adverse effects such as yolk sac oedema, pericardia oedema, haemorrhages, craniofacial abnormalities, premature hatch or inhibited growth was observed. Histological studies of hatched larvae did not reveal specific sublethal effects in tissues and organs. Developmental delays and subsequent embryo death were noticed at the period of eye pigmentation in affected groups. Early life-history stages of capelin are sensitive indicators of PAH impacts, but the mechanisms responsible for the toxic effects require further investigation. PMID- 22037119 TI - Altered neurophysiologic response to intermittent theta burst stimulation in Tourette syndrome. AB - BACKGROUND: The motor system in Tourette syndrome has been found to be abnormal in previous fine-motor and neurophysiologic studies. OBJECTIVE: This novel pilot study uses repetitive transcranial magnetic stimulation as a method to characterize the neurophysiology of the motor system in Tourette syndrome. METHOD: We investigated the modulation of cortical excitability in adult Tourette syndrome patients by measuring motor-evoked potential amplitudes before and after applying intermittent theta burst transcranial magnetic stimulation. RESULTS: Motor-evoked potential amplitude changes over 1 and 10 minutes after intermittent theta burst transcranial magnetic stimulation were greater in 11 healthy controls than 10 adult patients with Tourette syndrome (P = 0.004). CONCLUSIONS: This altered neurophysiologic response to intermittent theta burst stimulation may contribute to the understanding of motor cortical mechanisms in Tourette syndrome. PMID- 22037120 TI - Efficacy and safety of bifocal tDCS as an interventional treatment for refractory schizophrenia. PMID- 22037121 TI - Lack of clinically detectable acute changes on autonomic or thermoregulatory functions in healthy subjects after transcranial direct current stimulation (tDCS). AB - BACKGROUND: Neuromodulatory techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have been increasingly studied as possible treatments for many neurological and psychiatric disorders. tDCS is capable of inducing changes in regional cerebral blood flow in both cortical and subcortical structures, as shown by positron emission tomography studies, and might conceivably affect hypothalamic and autonomic nervous system functions. However, it remains unknown whether acute changes in autonomic or hypothalamic functions may be triggered by conventional tDCS protocols. OBJECTIVE/HYPOTHESIS: To verify whether tDCS, when performed with a bipolar cephalic montage, is capable of inducing acute changes in autonomic or hypothalamic functions in healthy subjects. METHODS: Fifty healthy volunteers were studied. tDCS was performed with the anode over the C3 position and the cathode over the right supraorbital region. Subjects received either real or sham tDCS. Parameters assessed before and after a 20-minute session included blood pressure, tympanic thermometry, hand skin temperature, heart rate and ventilatory rate. Plasma concentrations of cortisol were also measured in a sub-set of 10 participants. RESULTS: A repeated-measures, mixed-design ANOVA showed significant changes in hand skin temperature (P = .005) and cortisol levels (P < .001) after both real and sham stimulation. There were no statistically significant changes in any of the other measurements. CONCLUSIONS: The changes in hand temperature and cortisol levels, having occurred in both the sham and experimental groups, probably reflect a non-specific stress response to a new procedure. There were no significant changes in autonomic functions, ventilation rate or core body temperature that can be attributed to conventional tDCS applied to healthy volunteers. PMID- 22037122 TI - The relationship between TMS measures of functional properties and DTI measures of microstructure of the corticospinal tract. AB - BACKGROUND: Recently, a link between resting motor threshold (RMT) and local tissue microstructure, as indexed by fractional anisotropy (FA), was demonstrated in large parts of white matter. However, regions showing such correlations were generally found outside of the corticospinal tract (CST). Therefore, the question arises whether other electrophysiologic measurements could be more locally related to microstructural properties of the CST. In this study, we explored the relationship between such measurements and regional FA in a group of healthy volunteers. OBJECTIVE/HYPOTHESIS: We hypothesized that RMT might be more related to an overall susceptibility of white matter to TMS, whereas other electrophysiologic markers might be more specifically related to properties of the CST only. METHODS: Thirty-seven subjects were included. We studied RMT, active motor threshold (AMT), intensity to evoke a motor-evoked potential (MEP) of 1 mV (S1mV), MEP input-output curve (IO-curve), and central motor conduction time (CMCT) using transcranial magnetic stimulation, and FA of the corticospinal tract using diffusion tensor magnetic resonance imaging. We performed voxel-wise and TBSS correlation analysis between these electrophysiologic measurements and FA. In addition, we tested for significant correlation between these parameters and mean diffusivity (MD). RESULTS: On voxel-wise analysis, we did not detect significant correlations between any electrophysiologic parameter (RMT, AMT, S1mV, IO curve slope, CMCT) and FA. With TBSS, we detected correlations between FA and bilateral AMT, as well as left-hemispheric S1mV, but these correlations were found in locations unlikely to contribute to motor pathways. CONCLUSIONS: Although a relationship between structure and function has been shown in many other regions of the brain, it seems to be much more challenging to demonstrate such a relationship in the CST of healthy subjects. PMID- 22037123 TI - A practical guide to the use of repetitive transcranial magnetic stimulation in the treatment of depression. AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is currently emerging as a new treatment for patients with mood disorders. Research into the use of rTMS for the treatment of patients with depression has been conducted now for a period of greater than 15 years and a considerable body of knowledge has accumulated informing its use. OBJECTIVE: The aim of this paper was to review the use of various rTMS techniques for the treatment of depression and to provide practical suggestions to address the common issues encountered in the prescribing and administration of rTMS treatment. METHODS: These suggestions have been informed both by a review of the relevant literature and the experience of the authors in the treatment of many patients with depression with rTMS over a period of 10 years. RESULTS AND CONCLUSIONS: High-frequency rTMS applied to the left dorsolateral prefrontal cortex, using a set of parameters very similar to those originally described in the mid-1990s, is an effective treatment for patients with major depressive disorder. Other forms of stimulation, such as low-frequency stimulation applied to the right prefrontal cortex and bilateral approaches, may prove valuable but require evaluation in larger trials. Significant benefit appears likely to accumulate through the use of methods that involve a more reliable targeting of prefrontal brain regions. Suggestions are also made around the use of rTMS treatment as a maintenance therapy and in specific illness subgroups. PMID- 22037124 TI - Improved receptive and expressive language abilities in nonfluent aphasic stroke patients after application of rTMS: an open protocol case series. AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been identified as a potentially valuable tool for the rehabilitation of language impairment after left hemisphere (LH) stroke, in populations of persons with chronic aphasia. Applied to a homologue to Broca's area, rTMS is posited to modulate bilateral language networks, promoting measurable behavioral language change, in accordance with theories of transcallosal disinhibition arising from the damaged LH. OBJECTIVE/HYPOTHESIS: The current investigation is an open-label study, presenting detailed case and group presentations on a population of seven nonfluent aphasic participants. Behavioral language performance is presented on expressive and receptive language measures up to 8 months after a 10-day protocol of 1 Hz stimulation. This research aims to provide longitudinal behavioral language outcomes for persons with aphasia, subsequent to rTMS and supplement previous studies to inform the clinical efficacy of rTMS. RESULTS: In accordance with previous investigations, significant improvements in picture naming, spontaneous elicited speech and auditory comprehension were found. Time of testing was identified as a significant main effect. Significant improvements in picture naming accuracy and decreases in picture naming latency were also identified. The results demonstrate sustained language improvements up to 8 months subsequent to TMS application. CONCLUSIONS: The results of this investigation are consistent with the findings of previous research studies, reporting behavioral language changes after rTMS in nonfluent aphasia. Additional evidence is provided to demonstrate that rTMS may facilitate retrieval mechanisms involved in picture naming. PMID- 22037125 TI - A case report of daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for Alzheimer disease. PMID- 22037127 TI - Brain blood-flow change with acute vagus nerve stimulation in treatment refractory major depressive disorder. AB - BACKGROUND: Existing neuroimaging studies of vagus nerve stimulation (VNS) in treatment resistant major depression (TRMD) suggest that many brain regions (eg, prefrontal cortex, thalamus, cingulate cortex, insular cortex) associated with mood disorders undergo alterations in blood flow/metabolism. OBJECTIVE/HYPOTHESIS: Positron emission tomography (PET oxygen-15 labeled water or PET [(15)O] H(2)O) was used to identify changes in regional cerebral blood flow (rCBF) in response to immediate VNS in 13 subjects with TRMD. We hypothesized rCBF changes along the afferent pathway of the vagus and in regions associated with depression (eg, orbitofrontal cortex, amygdala, insular cortex). METHODS: Six 90-second PET [(15)O] H(2)O scans were performed on 13 subjects in a VNS off-on sequence. After normalization for global uptake and realignment to standard atlas space, statistical t images (P < .005) were used to evaluate rCBF change. RESULTS: VNS induced significant rCBF decreases in the left and right lateral orbitofrontal cortex and left inferior temporal lobe. Significant increases were found in the right dorsal anterior cingulate, left posterior limb of the internal capsule/medial putamen, the right superior temporal gyrus, and the left cerebellar body. Post hoc analysis found small-to-moderate correlations between baseline acute change in rCBF and antidepressant response after 12 months of VNS. CONCLUSIONS: Regions undergoing rCBF change in response to acute VNS are consistent with the known afferent pathway of the vagus nerve and models of brain network in depression. Larger studies assessing the correlation between acute stimulation patterns and antidepressant outcomes with VNS are needed. PMID- 22037126 TI - Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. METHODS: We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research. MAIN FINDINGS/DISCUSSION: We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS. PMID- 22037128 TI - Differences in the experience of active and sham transcranial direct current stimulation. AB - BACKGROUND: A limited number of studies have shown that modulation of cortical excitability using transcranial direct current stimulation (tDCS) is safe and tolerable. Few have directly evaluated whether sham and active stimulation are indistinguishable. OBJECTIVE: We aimed to demonstrate tDCS safety and tolerability in a large cohort, and to compare the occurrence and severity of side effects between sham and active stimulation sessions. METHODS: One hundred thirty-one healthy subjects undergoing 277 tDCS sessions rated on a 1 to 5 scale the perception of side effects during and after stimulation. Proportions of active and sham sessions associated with side effects were compared using Fisher exact test, and distributions of severity ratings were compared using the Kruskal Wallis test. RESULTS: No serious adverse effects occurred. Side effects most commonly reported were tingling (76%), itching (68%), burning (54%), and pain (25%). Side effect severity was mild, with fewer than 2% of responses indicating a severity > 3 on all questions except tingling (15%), itching (20%), burning (7%), pain (5%), and fatigue (3%) during stimulation. Rates of sensory side effects were statistically significantly higher in active stimulation sessions compared with sham sessions. No other stimulation parameters had a statistically significant impact on side effect occurrence. CONCLUSIONS: TDCS is a safe well tolerated technique with no evidence of risk for serious adverse effects. Sensory side effects are common, but the severity is typically low. Because sensory side effects are more frequent and more severe in active compared with sham tDCS, the current method of sham stimulation may not be an adequate control condition for some studies. PMID- 22037129 TI - The number of full-sine cycles per pulse influences the efficacy of multicycle transcranial magnetic stimulation. AB - BACKGROUND: Previous studies have shown that the efficacy of transcranial magnetic stimulation (TMS) to excite corticospinal neurons depends on pulse waveform. OBJECTIVE/HYPOTHESES: In this study, we examined whether the effectiveness of polyphasic TMS can be increased by using a pulse profile that consists of multiple sine cycles. METHODS: In eight subjects, single-pulse TMS was applied to the left primary motor hand area through a round coil attached to a stimulator device that generated polyphasic pulses consisting of one to six full-sine cycles with a cycle length of 86 MUs. In different blocks, we varied the number of sine cycles per pulse and recorded the motor-evoked potential (MEP) from the right first dorsal interosseus muscle. For each stimulus type, we determined resting motor threshold (RMT), stimulus-response curve (SRC), and mean MEP amplitude evoked at maximal stimulator output to assess the efficacy of stimulation. RESULTS: Multicycle pulses were more effective than a single full sine cycle in exciting corticospinal neurons. TMS with multicycle pulses resulted in lower RMT, larger MEP amplitudes at maximal stimulator output and a steeper slope of the SRC relative to a TMS pulse consisting of a single-sine cycle. The increase in efficacy was already evident when two full-sine cycles were used and did not increase further by adding more cycles to the TMS pulse. CONCLUSIONS: Increasing the number of full-sine cycles per pulse can improve the efficacy of TMS to excite corticospinal neurons, but there is no simple linear relationship between the number of cycles and TMS efficacy. PMID- 22037130 TI - Can repetitive transcranial magnetic stimulation prolong the antidepressant effects of sleep deprivation? AB - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been proposed for stabilizing the antidepressant effect of sleep deprivation (SD) by preventing the relapse after a night of recovery sleep. In this study, we aimed to replicate these data coming from a small pilot study in a larger patient sample. METHODS: Thirty-seven patients were randomly assigned to receive either active or sham rTMS on four consecutive days after one night of SD. The majority of the participants had experienced an antidepressant effect of SD in the past. At each rTMS session 1000 stimuli were applied over the left dorsolateral prefrontal cortex at 10 Hz with an intensity of 110% resting motor threshold. For sham stimulation, a sham-coil system was used. Treatment effects were assessed with a modified version of the Hamilton Depression Rating Scale and a self-report well being scale (BfS) before SD, after SD, during rTMS and 3 days after rTMS. RESULTS: SD led to a highly significant reduction of depressive symptoms in the whole group as reflected by a mean Hamilton Depression Rating Scales score reduction of 56% (with omission of sleep items). In both the active and the sham stimulated group, the symptom reduction remained stable for the whole observation period. No difference between active and sham rTMS was observed. CONCLUSIONS: SD is capable of inducing pronounced antidepressant effects. In contrast to a previous study, active rTMS was not superior to sham rTMS in stabilizing the antidepressant effects of SD, which was mainly due to a pronounced effect in the sham group in this study population. PMID- 22037131 TI - Neurophysiological investigation of congenital mirror movements in a patient with agenesis of the corpus callosum. AB - We describe a patient with complete agenesis of the corpus callosum and congenital mirror movements in which primary motor cortex (M1) excitability of both hemispheres was assessed with transcranial magnetic stimulation. Voluntary contraction of the index finger was associated with bilateral electromyographic activity in the first dorsal interosseus muscle. Motor-evoked potentials of identical latencies were produced bilaterally after unilateral M1 stimulation. Measures of intracortical inhibition and facilitation were within normal limits bilaterally although a shorter contralateral silent period was found for both hemispheres. Taken together, the current data suggest a pattern of M1 excitability very similar to that found in patients with congenital mirror movements and no other motor abnormality. PMID- 22037132 TI - Episode length and mixed features as predictors of ECT nonresponse in patients with medication-resistant major depression. AB - OBJECTIVES: This study aimed to ascertain predictors of nonresponse to electroconvulsive therapy (ECT) in a large sample of major depressive patients resistant to pharmacologic treatment. METHODS: A total of 208 depressive patients (31 with major depression [UP], 101 with bipolar disorder II [BP II], and 76 with bipolar disorder I [BP I] according to DSM-IV criteria) were included in the study and treated with bilateral ECT on a twice-a-week schedule. The patients were assessed before (baseline) and a week after the ECT course (final score) using the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Young Mania Rating Scale (YMRS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Improvement (CGI). Responders were defined as those patients with a reduction of at least 50% in HAM-D-17 score and a rating of 2 ("much improved") or 1 ("very much improved") in the CGI-Improvement subscale. RESULTS: At the end of the ECT course, 152 patients (64%) were classified as responders and 56 patients (36%) were classified as nonresponders. On backward stepwise logistic regression, bipolar subtype (odds ratio [OR]=17.85; 95% confidence level [CL]=1.786-178.407), higher mean baseline YMRS scores (OR=1.094; 95% CL=1.025 1.166), lower mean baseline HAM-D-17 scores (OR=0.928; 95% CL=0.860-1.002), and length of current episode (OR=1.047; 95% CL=1.009-1.086) were identified as statistically significant predictors of nonresponse. CONCLUSIONS: ECT was an effective treatment for approximately two-thirds of the patients with medication resistant depression who were included in this study. ECT nonresponse was associated with bipolar subtype, presence of manic symptoms during depression, slightly less severe depressive symptomatology, and protracted duration of the episode. PMID- 22037133 TI - Repetitive transcranial magnetic stimulation (rTMS) improves movement-related cortical potentials in autism spectrum disorders. AB - BACKGROUND: Motor impairments are common in autism spectrum disorders (ASD). Electrophysiologic studies reveal abnormalities in the preparation of movement; repetitive transcranial magnetic stimulation (rTMS) to key motor cortical sites may therefore be a useful technique for improving motor function in ASD. OBJECTIVE: To examine whether rTMS can improve electrophysiologic and behavioral indices of motor activity. METHODS: Eleven participants with ASD completed three sessions in which they were administered one of three rTMS conditions (left M1, supplementary motor area [SMA], sham) at 1 Hz for 15 minutes. Movement-related cortical potentials (MRCPs) were assessed before and after rTMS. RESULTS: rTMS to the SMA was associated with a gradient increase to the early component of MRCPs, whereas rTMS to left M1 produced a stronger gradient in the late component. CONCLUSIONS: rTMS appears to improve movement-related electrophysiologic activity in ASD, perhaps through an influence on cortical inhibitory processes. PMID- 22037134 TI - The effect of right vagus nerve stimulation on focal cerebral ischemia: an experimental study in the rat. AB - BACKGROUND: The aim of this study was to determine the effect of vagus nerve stimulation (VNS) on infarct size after transient and after permanent focal cerebral ischemia in rats and to test the hypothesis that VNS-induced neuroprotection is due to changes in cerebral blood flow. METHODS: Ischemia was produced by either temporary proximal middle cerebral artery occlusion (TMCAO) or permanent distal middle cerebral artery occlusion (PMCAO). Stimulating electrodes were implanted on the cervical part of the right vagus nerve, and electrical stimulation was initiated 30 minutes after the induction of ischemia and delivered for 30 seconds every 5 minutes for 1 hour. All the procedures were duplicated but no stimulus was delivered in control groups. Cerebral blood flow in the MCA territory was continuously monitored with laser speckle contrast imaging. A neurologic evaluation was undertaken after 24 hours of ischemia, and animals were euthanized and neuronal damage evaluated. RESULTS: Ischemic lesion volume was smaller in VNS-treated animals in both the temporary and permanent ischemic groups (P<.01). VNS-treated animals in TMCAO had better functional scores at 24 hours as compared with control animals (P<.01), but there were no statistically significant differences in the neurobehavioral scores in PMCAO (P=.089). Cerebral blood flow changes in the MCA territory during ischemia did not differ between the VNS-treated animals and control animals in either group. CONCLUSIONS: VNS offers neuroprotection against stroke in both temporary and permanent ischemia. Although the precise mechanism of this effect remains to be determined, alterations in cerebral blood flow do not appear to play a role. VNS could readily be translated to clinical practice. PMID- 22037135 TI - Time course and duration of changes in Kv7.2 and Kv11.1 mRNA expression in the hippocampus and piriform cortex following electroconvulsive stimulations. AB - BACKGROUND: A minimum of six electroconvulsive therapy (ECT) treatments has to be delivered to achieve sustained improvement in major depression. However, the mechanisms of the therapeutic actions of ECT are still debated. OBJECTIVE: We aimed to study the time course and duration of increased Kv7.2 and Kv11.1 mRNA expression in the hippocampus and piriform cortex (Pir) after electroconvulsive stimulation (ECS). METHODS: Adult male Sprague-Dawley rats received three ECS per week over 1, 2, or 3 weeks and were decapitated 3 days after the last stimulus. Additional groups of rats receiving nine ECS were sacrificed 7 or 28 days after the last ECS. In situ hybridization was used to measure Kv channel mRNA expression after ECS. RESULTS: Kv7.2 mRNA was increased in the hippocampus and Pir 3 days after both six and nine, but not after three ECS. This was also seen for Kv11.1 mRNA in Pir. These changes lasted for at least 7 days. CONCLUSIONS: These results indicate that the changes in Kv7.2 and Kv11.1 channels may contribute to the therapeutic effect of ECT. However, further research needs to be undertaken in this area to extend these findings. PMID- 22037136 TI - Transient increase of plasma concentrations of amyloid beta peptides after electroconvulsive therapy. AB - BACKGROUND: Electroconvulsive therapy (ECT) is applied to effectively treat depressive episodes, and it can be considered an ideal model of generalized seizures induced and performed under precisely controllable conditions. OBJECTIVE: We hypothesize that ECT causes a transiently increased blood-brain barrier permeability. METHODS: We measured plasma concentrations of amyloid beta (Abeta) peptides: 1-42, 1-40, x-42, and x-40 before ECT, within 30 minutes after 2, and 24 hours after ECT treatment in 33-36 sessions of n=13 different patients. RESULTS: We observed a significant increase of the plasma concentrations of all four peptides within 30 minutes after the ECT, followed by the normalization of the peptides concentrations 2 hours after the ECT. CONCLUSION: Different physiologic phenomena may be responsible for the transient increase of the Abeta peptides concentrations in plasma shortly after ECT session, and further studies are necessary to explain these mechanisms. For example, decreased integrity of the blood-brain barrier permeability, an increased release from neurons due to their activation or increased release from peripheral sources, like thrombocytes or muscles, or a combination of different factors must be taken into consideration. PMID- 22037137 TI - Cognitive behavioral therapy-related increases in cortical inhibition in problematic perfectionists. AB - BACKGROUND: Several lines of evidence suggest that cognitive behavioral therapy (CBT) is an effective treatment for depression and anxiety disorders. Evidence suggests that the therapeutic effects of CBT are related to neurophysiologic changes in the cortex, particularly gamma-aminobutyric acid (GABA) potentiation. Transcranial magnetic stimulation (TMS) represents a noninvasive method of measuring cortical inhibition, which is a neurophysiologic mechanism associated with the pathophysiology of several psychiatric disorders. OBJECTIVE/HYPOTHESIS: To demonstrate the effectiveness of a 12-week CBT intervention compared with a wait list control group measuring cortical inhibition in participants with pathologic perfectionism. Participants within the CBT group would demonstrate increases in cortical inhibition and improvements on clinical outcomes relative to the wait list control group. METHODS: Twenty-four right-handed perfectionists were randomly assigned to a 12-week CBT intervention or a wait list control group. Cortical inhibition was measured at pre- and postintervention with TMS paradigms specifically short-interval cortical inhibition and the cortical silent period, which index GABAA and GABAB receptor-mediated inhibitory neurotransmission, respectively. RESULTS: The CBT group demonstrated a significant potentiation of the cortical silent period when compared with the wait list control group. The CBT group demonstrated a decrease in anxiety sensitivity and automatic thoughts relative to the control group. CONCLUSIONS: These findings demonstrate that CBT tailored for perfectionism is accompanied by an increase in cortical inhibition of the motor cortex and positive changes on clinical outcomes. These findings provide compelling evidence for an association between positive CBT effects and a potentiation of GABAergic inhibitory neurotransmission. PMID- 22037138 TI - The involvement of posterior parietal cortex and frontal eye fields in spatially primed visual search. AB - BACKGROUND: Right posterior parietal cortex (rPPC) and frontal eye fields (FEF) are known to be involved in processing visuospatial attention. However, the functional involvement of these areas in spatial priming in complex conjunction visual search has yet to be determined. OBJECTIVE: This study aimed to examine the roles of rPPC and bilateral FEF in conjunction search when spatial ambiguity was reduced by priming the target location. METHODS: Participants completed a conjunction search task whereby the target location was random or else repeated from the previous trial. Transcranial magnetic stimulation was delivered to each one of the three sites of interest at a time, and task performance was compared with a sham condition. RESULTS: Spatial priming occurred for all conditions: search times were faster for primed relative to nonprimed trials. When the target appeared at a nonprimed location, stimulation over any of the three sites increased reaction times relative to the sham condition. However, when the target location was repeated, reaction time was only significantly increased by stimulation over the right FEF. CONCLUSIONS: rPPC and left FEF are only involved when the target location is random, suggesting that these areas are essential for resolving spatial ambiguity to localize targets. Conversely, right FEF contributes equally to visual search regardless of spatial priming. We propose that right FEF has a role in the integration of bottom up saliency and top down expectancy signals and is the node at which rPPC and/or left FEF is either recruited or not. PMID- 22037139 TI - Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation. AB - BACKGROUND: Evidence from recent clinical trials suggests that transcranial direct current stimulation (tDCS) may have potential in treating neuropsychiatric disorders. However, the optimal frequency at which tDCS sessions should be administered is unknown. OBJECTIVE/HYPOTHESIS: This study investigated the effects of daily or second daily tDCS sessions on motor cortical excitability, over a 5-day period. METHODS: Twelve healthy volunteers received daily or second daily sessions of tDCS to the left primary motor cortex over the study period, in a randomized, intraindividual crossover design. Motor cortical excitability was assessed before and after tDCS at each session through responses to transcranial magnetic stimulation. RESULTS: Over a fixed 5-day period, tDCS induced greater increases in MEP amplitude when given daily rather than second daily. Analyses showed that this difference reflected greater cumulative effects between sessions rather than a greater response to each individual tDCS session. CONCLUSIONS: These results demonstrate that in the motor cortex of healthy volunteers, tDCS alters cortical excitability more effectively when given daily rather than second daily over a 5-day period. PMID- 22037140 TI - Novel attempts to optimize vagus nerve stimulation parameters on serotonin neuronal firing activity in the rat brain. AB - BACKGROUND: Vagus nerve stimulation (VNS) is indicated for treatment-resistant epilepsy and depression. Electrophysiologic recordings in the rat brain have shown that VNS promptly increases the firing rate of NE neurons and subsequently that of 5-HT neurons. Thus far, it appears that the standard stimulation parameters currently used in depressed patients produce an optimal activation of 5-HT neurons. OBJECTIVE/HYPOTHESIS: This study was therefore aimed at investigating additional alterations of stimulation parameters to optimize VNS efficacy to further increase 5-HT neuronal activity. METHODS: Rats were implanted with a VNS device and stimulated for 14 days using standard (0.25 mA/20 Hz/500 microseconds/30 seconds ON-5 minutes OFF, continuously) or various stimulation parameters: extension of the OFF period (30 seconds ON every 10 to 30 minutes), the OFF and ON periods, discontinuous stimulation (12 hours per day using standard parameters), and burst stimulation modes. Rat dorsal raphe 5-HT neurons were recorded under chloral hydrate anesthesia. RESULTS: Both 12-hour stimulation periods for 14 days, and the 30-second stimulation every 10 or 15 minutes significantly increased the firing activity of 5-HT neurons to the same extent as standard parameters while the 30-minute intervals were ineffective. Stimulations in a burst mode and the pseudo-one-pulse stimulations also significantly increased 5-HT neuronal activity. CONCLUSIONS: These results indicate that less stimulation is sufficient to achieve the same VNS efficacy on 5-HT neuronal firing. These data may be relevant for patients using VNS because these new parameters could minimize or prevent side effects and increase battery life of the stimulator. PMID- 22037141 TI - Effects of repeated electroconvulsive shock on methamphetamine-induced behavioral abnormalities in mice. AB - BACKGROUND: Methamphetamine abuse and addiction can lead to impaired cognition and psychosis, and there is no effective treatment for methamphetamine-induced mental illnesses. OBJECTIVE: The aim of this study was to test whether repeated electroconvulsive shock (ECS) treatment has a therapeutic effect on methamphetamine-induced abnormal behavior in mice. METHODS: To test the effects of ECS on methamphetamine-induced psychosis, ICR mice were randomly assigned to administration with either chronic methamphetamine or saline injection, and then both groups underwent post-treatment with either six once-daily ECS treatments or parallel sham controls. Prepulse inhibition (PPI), the novel object recognition test (NORT) and behavioral sensitization were performed for behavioral evaluation between the groups. To test the effects of ECS on methamphetamine addiction, methamphetamine-induced conditioned place preference (CPP) was examined after ECS and drug-primed reinstatement in the other set of experiments. RESULTS: The animals receiving repeated ECS following pretreatment with methamphetamine showed significant improvement in PPI and NORT, but not in behavioral sensitization. In the CPP study, the ECS-treated animals achieved extinction of place preference, but relapsed after a low-dose reinstatement of methamphetamine. CONCLUSIONS: The results indicated that repeated ECS treatments can ameliorate impairment to the sensorimotor gating and recognition memory elicited by methamphetamine, and temporarily suppress the reinforcement induced by methamphetamine in mice. Our findings suggest electroconvulsive therapy (ECT) may have potential applications with regard to the treatment of methamphetamine psychosis and addiction. PMID- 22037142 TI - Epidural electrical stimulation to improve chronic poststroke aphasia: a 5-year follow-up. AB - BACKGROUND: Aphasia is an incapacitating deficit experienced by almost 25% of patients after a left hemispheric ischemic stroke. Spontaneous recovery is considered to be limited to a period of 3 to 6 months. Although speech therapy performed during the first weeks may speed up this process and enhance its outcome, beyond this period it fails to change the global prognosis. OBJECTIVE: We report a case of an unusual recovery of nonfluent chronic poststroke aphasia subsequent to extradural cortical stimulation. METHODS: A right-handed woman experienced aphasia and drug-resistant central poststroke facial pain after a left superficial Sylvian ischemic stroke at the age of 58 years old. Four years after the stroke, the patient was included in a clinical trial to establish the efficiency of epidural electric stimulation on neuropathic pain. As an improvement in her language performance was noted, a speech evaluation was added to the initial protocol to quantify the benefit. Twelve months after the surgical implantation, pain and language performance were assessed in a double-blind manner during two consecutive 1-month periods when the stimulator was randomly enabled or disabled. The same evaluation was performed after 5 years of stimulation. RESULTS: Eventually, epidural electric stimulation significantly and sustainably improved her lexical access and speech fluency. CONCLUSIONS: Cortical stimulation may offer a new approach for the treatment of late chronic poststroke aphasia. PMID- 22037143 TI - Secondary procedures after infrarenal abdominal aortic aneurysms endovascular repair with second-generation endografts. AB - BACKGROUND: To study the incidence, the types, and the results of secondary procedures performed after endovascular treatment of infrarenal abdominal aortic aneurysm (AAA). To compare the population of patients who underwent secondary procedure (P2) with the population of those who did not require it. MATERIAL AND METHODS: Between 1998 and 2008, this study included all the patients electively treated for AAA with stentgrafts that were still available on the market on January 1, 2009. Data were prospectively collected and retrospectively analyzed. The postoperative follow-up included at least a systematic computed tomography scan at 6, 12, 18, and 24 months and then every year. P2 were defined as any additionnal procedures performed to treat aneurysm related complications after initial stentgraft implantation. RESULTS: We studied 162 patients with a mean 40 +/- 31 months' follow-up. In 32 patients (19.7%), there were 46 P2, 3 of them were surgical conversion and 1 with endovascular conversion. Thirty-nine P2 were scheduled, and seven were performed in emergency. Nine patients underwent more than one P2. P2 was indicated for type II endoleak in 17 cases, 13 of them with a diameter increase; for type I endoleak in 10 cases; for AAA rupture in 3 cases; for occlusion or stentgraft stenosis in 13 cases; and for 1 type III endoleak, 1 endotension, and 1 femoro-femoral crossover bypass infection. Two ruptures occurred in patients who had undergone P2. The immediate technical success was 89.1%. At 30 days, morbidity was 10.9%, and there was no mortality. Survival rates at 3 and 5 years were respectively 85.2% and 71.9% in patients with secondary procedure and 70.6% and 47.5% in the others (p = 0.046). CONCLUSIONS: In patients treated for AAA with second generation stentgrafts, in the long term, secondary procedure rate was 19.7%. Survival rate for patients who underwent a secondary procedure was better, which was probably related to the fact that they were younger at the time of stentgraft implantation. Large AAA diameter was a secondary-procedure risk factor. PMID- 22037144 TI - Mixing in age-structured population models of infectious diseases. AB - Infectious diseases are controlled by reducing pathogen replication within or transmission between hosts. Models can reliably evaluate alternative strategies for curtailing transmission, but only if interpersonal mixing is represented realistically. Compartmental modelers commonly use convex combinations of contacts within and among groups of similarly aged individuals, respectively termed preferential and proportionate mixing. Recently published face-to-face conversation and time-use studies suggest that parents and children and co workers also mix preferentially. As indirect effects arise from the off-diagonal elements of mixing matrices, these observations are exceedingly important. Accordingly, we refined the formula published by Jacquez et al. [19] to account for these newly-observed patterns and estimated age-specific fractions of contacts with each preferred group. As the ages of contemporaries need not be identical nor those of parents and children to differ by exactly the generation time, we also estimated the variances of the Gaussian distributions with which we replaced the Kronecker delta commonly used in theoretical studies. Our formulae reproduce observed patterns and can be used, given contacts, to estimate probabilities of infection on contact, infection rates, and reproduction numbers. As examples, we illustrate these calculations for influenza based on "attack rates" from a prospective household study during the 1957 pandemic and for varicella based on cumulative incidence estimated from a cross-sectional serological survey conducted from 1988-94, together with contact rates from the several face-to-face conversation and time-use studies. Susceptibility to infection on contact generally declines with age, but may be elevated among adolescents and adults with young children. PMID- 22037145 TI - Interaction of the full-length Bax protein with biomimetic mitochondrial liposomes: a small-angle neutron scattering and fluorescence study. AB - In response to apoptotic stimuli, the pro-apoptotic protein Bax inserts in the outer mitochondrial membrane, resulting in the formation of pores and the release of several mitochondrial components, and sealing the cell's fate. To study the binding of Bax to membranes, we used an in vitro system consisting of 50nm diameter liposomes prepared with a lipid composition mimicking that of mitochondrial membranes in which recombinant purified full-length Bax was inserted via activation with purified tBid. We detected the association of the protein with the membrane using fluorescence fluctuation methods, and found that it could well be described by an equilibrium between soluble and membrane-bound Bax and that at a high protein-to-liposome ratio the binding seemed to saturate at about 15 Bax proteins per 50nm diameter liposome. We then obtained structural data for samples in this saturated binding regime using small-angle neutron scattering under different contrast matching conditions. Utilizing a simple model to fit the neutron data, we observed that a significant amount of the protein mass protrudes above the membrane, in contrast to the conjecture that all of the membrane-associated Bax states are umbrella-like. Upon protein binding, we also observed a thinning of the lipid bilayer accompanied by an increase in liposome radius, an effect reminiscent of the action of antimicrobial peptides on membranes. PMID- 22037146 TI - Eicosapentaenoic acid plays a role in stabilizing dynamic membrane structure in the deep-sea piezophile Shewanella violacea: a study employing high-pressure time resolved fluorescence anisotropy measurement. AB - Shewanella violacea DSS12 is a psychrophilic piezophile that optimally grows at 30MPa. It contains a substantial amount of eicosapentaenoic acid (EPA) in the membrane. Despite evidence linking increased fatty acid unsaturation and bacterial growth under high pressure, little is known of how the physicochemical properties of the membrane are modulated by unsaturated fatty acids in vivo. By means of the newly developed system performing time-resolved fluorescence anisotropy measurement under high pressure (HP-TRFAM), we demonstrate that the membrane of S. violacea is highly ordered at 0.1MPa and 10 degrees C with the order parameter S of 0.9, and the rotational diffusion coefficient D(w) of 5.4MUs(-1) for 1-[4-(trimethylamino)pheny]-6-phenyl-1,3,5-hexatriene in the membrane. Deletion of pfaA encoding the omega-3 polyunsaturated fatty acid synthase caused disorder of the membrane and enhanced the rotational motion of acyl chains, in concert with a 2-fold increase in the palmitoleic acid level. While the wild-type membrane was unperturbed over a wide range of pressures with respect to relatively small effects of pressure on S and D(w), the DeltapfaA membrane was disturbed judging from the degree of increased S and decreased D(w). These results suggest that EPA prevents the membrane from becoming hyperfluid and maintains membrane stability against significant changes in pressure. Our results counter the generally accepted concept that greater fluidity is a membrane characteristic of microorganisms that inhabit cold, high-pressure environments. We suggest that retaining a certain level of membrane physical properties under high pressure is more important than conferring membrane fluidity alone. PMID- 22037147 TI - Concepts of healthful food among low-income African American women. AB - OBJECTIVE: Describe beliefs about what makes foods healthful among low-income African American women. METHODS: In one-on-one interviews, 28 low-income African American mothers viewed 30 pairs of familiar foods and explained which food in the pair was more healthful and why. Responses were grouped into codes describing concepts of food healthfulness. RESULTS: Nutrient content, physical effects of food, and food categories were used to judge the healthfulness of foods. Fruits, vegetables, and dairy foods were considered the most healthful and starchy foods the least healthful because they were believed to cause weight gain. Beliefs about which foods contain which nutrients and which foods have particular physical effects varied widely across participants. CONCLUSIONS AND IMPLICATIONS: Participants demonstrated awareness of which foods are healthful but lacked understanding of why those foods are more healthful than others. Knowledge about the health effects of foods may be necessary to motivate individuals to choose healthful foods. PMID- 22037148 TI - Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study. AB - To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive miRNAs. The potential targets for those miRNAs were also predicted by computational programs. Fourteen of 866 human miRNAs exhibited at least 1.8-fold difference in the ratio of expression level before and after stimulation with PPD between the ATB and HC groups. The qRT-PCR study validated the findings from microarray-based screening, in which miR-155 exhibited a fold change of 1.4 in the HC group and 3.7 in the ATB group upon PPD stimulation (p < 0.0001); miR-155* exhibited a fold change of 1.9 in the HC and 4.6 in the ATB group (p < 0.005). In ROC plots, the area under the curve was 0.8972 for miR-155 and 0.7945 for miR-155*. The background expression of these 2 microRNAs exhibited no differences between the ATB and HC groups. miR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens. PMID- 22037149 TI - The role of the gut/brain axis in modulating food intake. AB - Peptide hormones released from the gastrointestinal tract communicate information about the current state of energy balance to the brain. These hormones regulate appetite and energy expenditure via the vagus nerve or by acting on key brain regions implicated in energy homeostasis such as the hypothalamus and brainstem. This review gives an overview of the main gut hormones implicated in the regulation of food intake. Research in this area has provided novel targets for the pharmacological treatment of obesity. This article is part of a Special Issue entitled 'Central Control Food Intake' PMID- 22037150 TI - Chemical burns--an historical comparison and review of the literature. AB - Chemical burns represent a small proportion of cutaneous burn with an incidence of up to 10.7%, but have been reported to account for up to 30% of all burn deaths. A review of the literature shows incidences ranging from 2.4% to 10.7%, with a substantial predominance in males. Adult patients with a burn referred to our Regional Burns Centre, over an eight-year period, were identified. 185 chemical burns were recorded (7.9%). The mean age of patient was 40 years (range 16-81 years) and male to female ratio was 6.4:1. Over three-quarters of chemical injuries occurred in the domestic or industrial setting. Acids caused 26% of all chemical burns and alkalis caused 55%. A previous study from the same centre highlights a change in the demographics of chemical burn over the last 25 years. The proportion of chemical burns has risen from 2.7% to 7.9%. Chemical burns occurring in an industrial setting, have dropped, whilst the number of domestic chemical burns has increased by over three times. This change reflects the improved industrial health and safety policy in recent years. The move from the industrial setting to the domestic has implications for future regulations. PMID- 22037151 TI - Substrate stiffness regulates the proliferation, migration, and differentiation of epidermal cells. AB - The aim of this study was to investigate the role of substrate stiffness on the proliferation, migration, and differentiation of epidermal cells. To investigate the effects of substrate stiffness on wound healing, epidermal cells were chosen and inoculated on silicone substrate with different values of Young's modulus of elasticity. The cell growth curve, MTT method, and cell cycle detection were used to investigate proliferation, and the scratch test was used to investigate cell migration. Fluorescence flow cytometry was used to study epidermal cell differentiation. The proliferation and migration of epidermal cells favoured stiffer surfaces. A highly stiff surface stimulated epidermal cell proliferation and migration and increased re-epithelialisation, but inhibited differentiation. The candidate pathways mediating epidermal cell proliferation and migration are linked to cell anchoring to substrates by integrin-mediated focal adhesion. PMID- 22037152 TI - The effect of valproic acid in alleviating early death in burn shock. AB - The aim of this study was to examine whether administration of valproic acid (VPA) improves blood circulation and survival after lethal burn shock. Forty adult male Beagle dogs underwent a 50% TBSA full-thickness flame injury. In the first 24 h after burn, animals were randomly divided into four groups: NR group received no treatment. VPA group and 2M2P(2-methyl-2-pentenoic acid) group received either VPA or 2M2P (100 mg of the either drug in 20 mL of normal saline) intravenously. VR group received intravenous infusion of lactated Ringer's solution according to Parkland formula. In the second 24 h after burn the animals of all groups received delayed IV fluid resuscitation. Hemodynamic variables and biochemical parameters were determined with animals in the conscious and cooperative state. From 4 h after burn on, the levels of mean arterial pressure, cardiac index, plasma volume and intestinal mucosal blood perfusion in VPA group were significantly higher, and the levels of parameters of organ function and serum tumor necrosis factor-alpha were lower than those in NR group and 2M2P group (all P<0.05). Survival at 72 h after burn was in following order: VR (100%)>VPA (60%)>2M2P (30%)>NR (10%). Our results showed that histone deacetylace inhibitor (HDACI) valproic acid significantly improved hemodynamics, intestinal perfusion, and the survival rate after lethal burn shock. The mechanism may be attributable partly to the lowering of the level of proinflammatory factors, ameriolation of vasopermeability-induced visceral edema, reduction of blood volume loss, and protection of vital organs through inhibition of histone deacetylase activity of cell of vital organs. PMID- 22037153 TI - PCT as a diagnostic and prognostic tool in burn patients. Whether time course has a role in monitoring sepsis treatment. AB - OBJECTIVE: To evaluate the diagnostic and prognostic performance of inflammatory markers for septic and non septic (localized) bacterial infections in patients with severe burn. METHODS AND RESULTS: Data of 145 patients were prospectively included in this study. Serum procalcitonin and other inflammatory markers were measured within 24 h after burn and daily thereafter. Maximum procalcitonin (p=0.004) was independent predictors of outcome in logistic regression analysis. PCT thresholds of 1.5 ng/ml, 0.52 ng/ml and 0.56 ng/ml had adequate sensitivity and specificity to diagnose sepsis, respiratory tract and wound infections respectively. A threshold value of 7.8 ng/ml in PCT concentration on day 3 was associated with the effectiveness of the sepsis treatment with an AUC of 0.86 (95% CI 0.69-1.03, p=0.002). C-reactive protein levels and WBCs showed no significant change over the first 3 days in the patients with successfully treated sepsis (p=0.93). CONCLUSION: The maximum procalcitonin level has prognostic value in burn patients. PCT can be used as a diagnostic tool in patients with infectious complications with or without bacteremia during ICU stay. Daily consecutive PCT measurements may be a valuable tool in monitoring the effectiveness of antibiotic therapy in burn ICU patients. PMID- 22037155 TI - Cerebrovascular autoregulation among very low birth weight infants. PMID- 22037156 TI - Use of propranolol for treatment of hemangiomas in PHACE syndrome. AB - We report the case of a 29-week preterm infant with PHACE (posterior fossa malformations, hemangionas, arterial anomalies, cardiac anomalies, eye anomalies) syndrome. PHACE syndrome is a neurocutaneous disorder with large facial segmental hemangionas associated with anomalies of the brain, eye, heart and aorta. The hemangiomas in our patient were problematic, distorting the airway and interfering with respirations to the point of requiring mechanical ventilation. Consultation with several different centers with medical expertize in treatment of congenital hemangiomas revealed different views on the best management strategy. In this infant, the hemangiomas progressed with failure to involute despite currently recommended therapy including corticosteroids and vincristine. Therefore, the infant was treated with propranolol and had significant regression of the hemangiomas. The use of propranolol for the treatment of infantile hemangiomas is reviewed. PMID- 22037157 TI - Familial recurrence of congenital heart diseases. AB - Familial recurrence of congenital heart disease (CHD), in particular, d transposition of great arteries (d-TGA) is rare. However, there have been several reports in the literature of sibling recurrence of total anomalous pulmonary venous return (TAPVR). This is the first case report in the literature, describing mother to offspring recurrence of d-TGA. We describe two cases of non syndromic CHD with mother to offspring and sibling recurrence. The first case is an antenatally diagnosed d-TGA on fetal echocardiogram at 25 weeks of gestational age in the offspring of a 30-year-old mother with d-TGA. The second case is a sibling reoccurrence of TAPVR diagnosed antenatally at 30 weeks of gestational age, with supradiaphragmatic TAPVR on fetal echocardiogram in a mother, whose first child was diagnosed with infradiaphragmatic TAPVR in infancy. PMID- 22037158 TI - The evolution of neonatal resuscitation training. PMID- 22037159 TI - Pumped shot noise in adiabatically modulated graphene-based double-barrier structures. AB - Quantum pumping processes are accompanied by considerable quantum noise. Based on the scattering approach, we investigated the pumped shot noise properties in adiabatically modulated graphene-based double-barrier structures. It is found that compared with the Poisson processes, the pumped shot noise is dramatically enhanced where the dc pumped current changes flow direction, which demonstrates the effect of the Klein paradox. PMID- 22037160 TI - Oncogene- and tumor suppressor gene-mediated suppression of cellular senescence. AB - Data accumulating during the last two decades suggest that tumorigenesis is held in check by two major intrinsic failsafe mechanisms; apoptosis and cellular senescence. While apoptosis is a programmed cell death process, cellular senescence, which is the focus of this article, is defined as irreversible cell cycle arrest. This process is triggered either by telomere erosion or by acute stress signals including oncogenic stress induced by overactive oncogenes or underactive tumor suppressor genes. The outcome of this is often replication overload and oxidative stress resulting in DNA damage. Oncogenic stress induces at least three intrinsic pathways, p16/pRb-, Arf/p53/p21- and the DNA damage response (DDR)-pathways, that induce premature senescence if the stress exceeds a threshold level. Oncogene-induced senescence (OIS) is frequently observed in premalignant lesions both in animal tumor models and in human patients but is essentially absent in advanced cancers, suggesting that malignant tumor cells have found ways to bypass or escape senescence. This review focuses on cell autonomous mechanism by which certain oncogenes, tumor suppressor genes and components of the DDR/DNA-repair machinery suppress senescence - mechanisms that are exploited by tumor cells to evade senescence and continue to multiply. In this way, tumor cells become addicted to the continuous activity of senescence suppressor proteins. However, some senescence pathways, although under suppression, may remain intact and can be re-established if senescence suppressor proteins are inactivated or if senescence inducers are reactivated. This can hopefully form the basis for a "pro-senescence therapy" strategy to combat cancer in the future. PMID- 22037161 TI - The results of reverse-flow island flaps in pulp reconstruction. AB - OBJECTIVE: The aim of this study was to retrospectively review the results of homodigital reverseflow proximal or middle phalanx dorsal skin island flaps. METHODS: We reviewed the overall results of 67 dorsal skin flap reconstructions performed on 61 proximal phalanxes and 6 middle phalanxes at our hospital during an 11 year period. The results were evaluated with static two point discrimination, Semmes-Weinstein monofilament test, occurrence of nail deformities, loss of interphalangeal joint motion, scar appearance of flap donor area, the incidence of vascular insufficiency in postoperative period, and subjective evaluation of patient satisfaction. RESULTS: The highest incidence of defect types were palmar oblique pulp defects in 18 patients (26.8%), transverse pulp defects in 16 patients (23.8%), and hemipulp oblique amputations in 11 patients (16.4%). Crush injuries were the cause of injury in 66% of patients. The average followup time was 40 months and long-term results were available in 21 patients. Total necrosis of flap in one patient (1.4%), superficial epidermolysis in 4 patients (5.9%), and nail deformity in 4 patients (5.9%) were seen. According to Semmes-Weinstein monofilament test results, protective sensation was achieved in 76% of patients. Static two point discrimination data showed variable distribution between 2 mm and 11 mm. The subjective patient satisfaction level was 95%. CONCLUSION: Homodigital reverse-flow proximal or middle phalanx dorsal skin island flaps give satisfactory cosmetic and sensorial results outside the pinch area, even if the dorsal branch of the digital nerve is not included. PMID- 22037162 TI - [Resources and models for diabetic foot care in Catalonia (Spain): a descriptive study on areas of improvement]. AB - OBJECTIVES: To identify areas of improvement in diabetic foot care as regards the availability of materials and specialties in primary and secondary care. To determine the model of care for surgical centres and hospitals caring for diabetic foot problems and their relation to amputations. DESIGN: Cross-sectional study SETTING AND PARTICIPANTS: Random sample of 36 basic health areas (BHA) and all hospital surgery centres in Catalonia (Spain). MEASUREMENTS: Information was collected by structured interview of managers of each centre on: availability of specialists, material off-loading and examination. The models were established according to the classification of Van Acker, and amputations from hospital discharge records. RESULTS: An endocrinologist was available in 36.1% [confidence interval (CI) 95%:19.0-53.2] of the BHA and 11.1% [95% CI: 3.1-26.1] had a podiatrist,100% [95% CI: 90.3-100.0] had Doppler, 91.7% [95% CI:77.5-98.2] a monofilament, 5.6% [95% CI: 0.7-18.7] a quantitative tuning fork, 11.1% [95% CI:3,1-26, 1] material off-loading, and 8.3% [95% CI: 1.8 - 22.5] a specialist reference centre. A total of 85 surgical centres and hospitals dealt with these problems: 11(13.0%) excellent model, 29 (34.1%) intermediate and 45 (52.9%) basic/insufficient. Centres with a basic model/insufficient performed 12.5% of the amputation, intermediate models, 56.4%, and 31.1% in excellent models. CONCLUSIONS: The proportion of ABS with materials, specialists and/or specialist reference centres was low. The basic/insufficient model was the most common among surgical/hospital centres. Most amputations were performed in centres with excellent and intermediate model; nevertheless, a considerable percentage was performed in centres with basic/insufficient models. PMID- 22037163 TI - Improving global maternal health: progress, challenges, and promise. AB - PURPOSE OF REVIEW: This review discusses the unprecedented global commitment to improve maternal health and scientific advancements in the field achieved during the last year. RECENT FINDINGS: Achievements at political, scientific, and programmatic levels targeted at improving maternal health, especially in low resource settings, are described. Remaining challenges are discussed and the most promising areas of research and practice aimed at addressing these challenges are identified. SUMMARY: For the first time in decades, it is evident that progress in reducing mortality on a global scale is possible. Results showing increases in coverage of key maternal health interventions and the establishment of a system for promoting accountability are key determinants of that progress. PMID- 22037164 TI - Partial breast radiation for early-stage breast cancer. AB - PURPOSE OF REVIEW: This review is to provide an update on the current status of partial breast irradiation (PBI) for women presenting with early-stage breast cancer, as an alternate radiation technique to fractionated, whole breast radiation, following conservation surgery. As more women are asking for and receiving this treatment, both on and off protocols, understanding recent additions to the literature is important to physicians caring for this patient population. RECENT FINDINGS: Newly published retrospective studies, with follow up times out to 10 years and the status of both recently completed and still open large prospective phase III trials will be covered, with emphasis on unexpected side effects reported, and some hypothesis-generating radiobiology observations. A recent consensus treatment guideline for PBI use is also discussed. SUMMARY: Selected retrospective studies continue to report outcomes matching those achieved with whole breast radiation; however, results from large prospective randomized trials comparing PBI to whole breast radiation have been reported only with short follow-up times, or in two studies, are still pending. A recent consensus guideline is useful at present in selecting patients for discussion of this treatment. PMID- 22037165 TI - Screening mammography in women less than age 50 years. AB - PURPOSE OF REVIEW: For women aged 40-49 years, to describe the benefits and harms of performing screening mammography, accuracy of digital mammography, and new evidence on the effectiveness of risk-based screening. RECENT FINDINGS: New data support a 15% reduction in breast cancer mortality for women aged 40-49 years after 10 years of screening; however, the absolute benefit is small and not outweighed by important harms. Digital mammography is more sensitive, but less specific than film mammography in women aged 40-49 years. Risk-based screening that identifies and screens women aged 40-49 years with breast cancer risk similar to an average-risk woman aged 50-59 years results in similar benefits and harms of screening these high-risk women as screening average-risk 50-year-old women. SUMMARY: Practitioners should discuss with women aged 40-49 years the benefits and harms of undergoing screening mammography before offering them screening. If women elect to undergo screening mammography, they should undergo biennial screening with digital mammography. Targeting screening for those women aged 40-49 years with risk factors that substantially increase the risk of breast cancer, such as high breast density, family history of breast cancer, and history of benign breast biopsy, could maximize the benefits and minimizes the harms of screening this age group. PMID- 22037166 TI - Short fusion strategy for Lenke type 1 thoracic curve using pedicle screw fixation. AB - STUDY DESIGN: A retrospective case-control study OBJECTIVE: Short fusion using pedicle screws (PSs) with an attempt to attain maximum correction of the main thoracic curve was conducted for patients with a Lenke type 1 curve, to prevent postoperative left shoulder elevation. The outcomes were compared with those of conventional surgery. SUMMARY OF BACKGROUND DATA: Excessive correction of the main thoracic curve by PSs causes problematic left shoulder elevation even in a Lenke type 1 curve. METHODS: Thirty-eight patients (3 male, 35 female, mean age 16.2 years, mean follow-up 24 mo) with Lenke type 1 curve underwent posterior corrective surgery using PSs. The upper instrumented vertebra was 1 level below the end vertebra in 14 patients (short, S group), and it was at the end vertebra in 24 patients (conventional, C group). There was no difference in the preoperative Cobb angle (51.8 vs. 58.0) or curve flexibility (49.7 vs. 46.1) between the 2 groups. Radiographic results, perioperative data, and scoliosis research society 22 scores were compared between the 2 groups. RESULTS: The postoperative Cobb angle of the main curve after surgery was 13.2+/-5.7 degrees in the S group and 10.6+/-7.3 degrees in the C group (not significant). The clavicle angle was -2.1+/-2.8 degrees versus -2.7+/-2.6 degrees before surgery (not significant), and 0.8+/-2.3 versus 3.8+/-2.4 after surgery (P<0.05). The number of fused vertebrae, mean surgical time, and estimated blood loss were significantly lower in the S group than in the C group. The scoliosis research society 22 score at follow-up was not different between the 2 groups. CONCLUSIONS: The short fusion strategy for a Lenke type 1 curve can produce equivalent correction of the main curve and clinical outcomes to conventional fusion strategy with less surgical time and blood loss, while maintaining better shoulder balance. PMID- 22037167 TI - The influence of thoracic inlet alignment on the craniocervical sagittal balance in asymptomatic adults. AB - STUDY DESIGN: A prospective radiographic study. OBJECTIVES: To analyze the relationship between craniocervical sagittal balance and thoracic inlet (TI) alignment and to present the parameters that would help predict physiological lordosis of the cervical spine. SUMMARY OF BACKGROUND DATA: The physiological cervical lordosis (CL) and related factors has not been clearly defined yet. No studies have reported correlations between TI alignment and sagittal balance of the cervical spine. METHODS: Cervical spine lateral radiograph of 77 asymptomatic adult volunteers (aged between 21 and 50 y) were taken to analyze the following parameters. (1) Thoracic inlet parameters: thoracic inlet angle (TIA), T1 slope, neck tilting (NT); (2) cervical spine parameters: C0-2 angle, C2-7 angle, % ratio of (C0-2/C0-7 angle), (C2-7/C0-7 angle), and cervical tilting; (3) cranial parameters: C0 angle, cranial offset, and cranial tilting. Statistical analysis was performed using the Pearson correlation coefficients and multiple regression analysis. RESULTS: The mean TIA, T1 slope, NT were 69.5, 25.7, and 43.7, respectively. The mean C0-2 angle, C2-7 angle, C0 angle, cranial offset, cervical tilting, and cranial tilting were -22.4 degrees, -9.9 degrees, -9.3 degrees, 20.9 mm, 18 degrees, and 7.7 degrees, respectively. The ratio of C0-2:C2-7 angle was maintained as 77:23% and cervical tilting:cranial tilting was 70.2:29.8%. A significant correlation was found between TIA and T1 slope (r=0.694), T1 slope and C2-7 angle (r=-0.624), C2-7 angle and C0-2 angle (r=-0.547), C0-2 angle and cranial offset (r=-0.406). CONCLUSIONS: The thoracic inlet alignment had significant correlations with craniocervical sagittal balance. To preserve physiological NT around 44 degrees, large TIA increased T1 slope and CL and vice versa. TIA and T1 slope could be used as parameters to predict physiological alignment of the cervical spine. The results of this study may serve as baseline data for the evaluation of sagittal balance or planning of a fusion angle in the cervical spine. PMID- 22037168 TI - The roles of activin A and its binding protein, follistatin, in inflammation and tissue repair. AB - Activin A, a member of the transforming growth factor-beta superfamily of cytokines, is a critical controller of inflammation, immunity and fibrosis. It is rapidly released into the blood following a lipopolysaccharide challenge in experimental animals, through activation of the Toll-like receptor 4 signalling pathway. Blocking activin action by pre-treatment with its binding protein, follistatin, modifies the inflammatory cytokine cascade, and reduces the severity of the subsequent inflammatory response and mortality. Likewise, high serum levels of activin A are predictive of death in patients with septicaemia. However, activin A has complex immunomodulatory actions. It is produced by inflammatory macrophages, but can regulate either pro- or anti-inflammatory responses in these cells, depending on their prior activation status. Activin A is also produced by Th2 cells, and stimulates antibody production by B cells and the development of regulatory T cells. Production of activin A during inflammatory responses stimulates fibrosis and tissue remodelling, and follistatin inhibits these actions of activin A. The modulation of activin by follistatin may represent an important therapeutic target for the modulation and amelioration of inflammatory and fibrotic disorders. PMID- 22037169 TI - Molecular bases of endometrial cancer: new roles for new actors in the diagnosis and the therapy of the disease. AB - Endometrial carcinoma (EC) is the most commonly diagnosed gynecologic malignancy in the western world. The majority of these cancers are curable, but a subset about 15-20% of endometrial tumors exhibits an aggressive phenotype. Based on clinic-pathological and molecular characteristics, EC has been classified into two groups: Type I estrogen-dependent adenocarcinomas, which have a good prognosis and an endometrioid histology, and Type II or non-estrogen-dependent EC associated with poor prognosis and non-endometrioid histology. EC develops as a result of a stepwise accumulation of alterations that seem to be specific of each histological type. However, more knowledge is needed to better understand the differences in the biology and the clinical outcome of EC. We would like to highlight the need to explore new potential biomarkers of EC as a tool for the detection and monitoring of aggressive endometrial tumors that, at the same time, will allow us to develop novel and more selective molecular targeted therapies against EC. PMID- 22037171 TI - The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA. AB - Tfam (transcription factor A, mitochondrial), a DNA-binding protein with tandem high-mobility group (HMG)-box domains, has a central role in the expression, maintenance and organization of the mitochondrial genome. It activates transcription from mitochondrial promoters and organizes the mitochondrial genome into nucleoids. Using X-ray crystallography, we show that human Tfam forces promoter DNA to undergo a U-turn, reversing the direction of the DNA helix. Each HMG-box domain wedges into the DNA minor groove to generate two kinks on one face of the DNA. On the opposite face, a positively charged alpha-helix serves as a platform to facilitate DNA bending. The structural principles underlying DNA bending converge with those of the unrelated HU family proteins, which have analogous architectural roles in organizing bacterial nucleoids. The functional importance of this extreme DNA bending is promoter specific and seems to be related to the orientation of Tfam on the promoters. PMID- 22037170 TI - An asymmetric interface between the regulatory and core particles of the proteasome. AB - The Saccharomyces cerevisiae proteasome comprises a 19-subunit regulatory particle and a 28-subunit core particle. To be degraded, substrates must cross the core particle-regulatory particle interface, a site for complex conformational changes and regulatory events. This interface includes two aligned heteromeric rings, one formed by the six ATPase (Rpt) subunits of the regulatory particle and the other by the seven alpha subunits of the core particle. The Rpt C termini bind to intersubunit cavities in the alpha-ring, thus directing core particle gating and proteasome assembly. We mapped the Rpt C termini to the alpha subunit pockets, using a cross-linking approach that revealed an unexpected asymmetry: one side of the ring shows 1:1 contacts of Rpt2-alpha4, Rpt6-alpha3 and Rpt3-alpha2, whereas on the opposite side, the Rpt1, Rpt4 and Rpt5 tails each cross-link to multiple alpha pockets. Rpt-core particle cross-links are all sensitive to nucleotides, implying that ATP hydrolysis drives dynamic alterations at the core particle-regulatory particle interface. PMID- 22037172 TI - Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter. AB - Human mitochondrial transcription factor A, TFAM, is essential for mitochondrial DNA packaging and maintenance and also has a crucial role in transcription. Crystallographic analysis of TFAM in complex with an oligonucleotide containing the mitochondrial light strand promoter (LSP) revealed two high-mobility group (HMG) protein domains that, through different DNA recognition properties, intercalate residues at two inverted DNA motifs. This induced an overall DNA bend of ~180 degrees , stabilized by the interdomain linker. This U-turn allows the TFAM C-terminal tail, which recruits the transcription machinery, to approach the initiation site, despite contacting a distant DNA sequence. We also ascertained that structured protein regions contacting DNA in the crystal were highly flexible in solution in the absence of DNA. Our data suggest that TFAM bends LSP to create an optimal DNA arrangement for transcriptional initiation while facilitating DNA compaction elsewhere in the genome. PMID- 22037173 TI - The effect of epsilon-aminocaproyl-S-benzyl-L-cysteine on the t-PA activity of human saliva. AB - PURPOSE: The aim of this work was to study the effect of the synthetic antifibrinolytics: epsilon-aminocaproic acid (EACA), tranexamic acid (AMCHA) and epsilon-aminocaproyl-S-benzyl-L-cysteine (H-EACA-S-Bzl-L-Cys-OH) on the fibrinolytic activity of saliva in order to obtain new data on the activity of saliva tissue plasminogen activator (t-PA). MATERIAL AND METHODS: Saliva samples were obtained from healthy volunteers. Saliva, precipitate and supernatant were tested 1hr, 4 hrs and 6hrs after collection. The effect of the synthetic antifibrinolytics was examined with the use of the clot lysis time determination. RESULTS: All examined compounds inhibited the fibrinolytic activity of saliva 1hr after collection. H-EACA-S-Bzl-L-Cys-OH was the most active inhibitor. After 6 hours in room temperature only this compound showed a certain possibility to prolong the clot lysis time. CONCLUSIONS: The obtained results may indicate the possibility of the difference in specificity between the activities of t-PA of saliva and recombinant tissue plasminogen activator activities. It may explain the unexpected high inhibitory activity of H-EACA-S-Bzl-L-Cys-OH in our study. PMID- 22037174 TI - Value of gastrin-17 in detecting antral atrophy. AB - PURPOSE: Decreased plasma gastrin-17 (G-17), particularly after protein stimulation, is indicative of atrophy in the antral stomach mucosa. Available data on the value of this biomarker is inconclusive. Our study was aimed to evaluate the performance of the G-17 test in Caucasian and Asian patients for antral atrophy evaluation either in fasting state or after protein stimulation. MATERIAL/METHODS: 241 dyspeptic patients aged 55 and above from Latvia (125), Lithuania (76) and Taiwan (40) were enrolled. G-17 levels were detected in plasma samples obtained either during fasting or after a protein-rich test meal. Levels <1 pmol/L at fast and <5 pmol/L after stimulation were considered indicative of atrophy. RESULTS: The sensitivity of the test was 15.8%, its specificity 88.7%, and the overall accuracy 83% in the fasting state, and 36.8, 86.5, and 82.6%, respectively, after stimulation. In the Caucasian subgroup, the corresponding figures were 15.4, 91.5, and 86.6% in the fasting state and 30.8, 92.6, 88.6% after stimulation; but for the Asian subgroup the corresponding figures were 16.7, 73.5, and 65% (fasting) and 50, 52.9, and 52.5% (stimulated). CONCLUSIONS: The performance of G-17 was better after protein stimulation. G-17 was highly specific in the Caucasian, but not in the Asian subgroups. Still the low test sensitivity either at fast or following protein stimulation does not allow us to recommend it for wide screening purpose to diagnose antral atrophy. PMID- 22037175 TI - Comparison of the long-term effectiveness of physiotherapy programs with low level laser therapy and pulsed magnetic field in patients with carpal tunnel syndrome. AB - PURPOSE: The aim of the study was to compare the long term effects of low - level laser therapy (LLLT) and pulsed magnetic field (PMF) in the rehabilitation of patients with carpal tunnel syndrome (CTS). METHODS: The study included 38 patients with idiopathic CTS, confirmed by electroneurographic (ENG) examination. All patients were randomly assigned to 2 groups: group L (18 patients) treated with LLLT and group M (20 patients) with PMF therapy. Clinical assessment, including day and night pain, the presence of paresthesia, functional tests (Phalen, Tinel, armband tests) and pain severity according to the Visual Analogue Scale (VAS) was conducted before treatment, after the first series of 10 sessions, after a two-week break, after the second series of 10 sessions and six months after the last series. RESULTS: After LLLT a significant reduction of day and night pain was observed at each stage of treatment and 6 months after the last series (p<0.05). However, in group M, a significant reduction of both day and night pain was demonstrated only after the second series (p<0.05). A reduction of the incidence of Phalen's symptoms were noticed in both groups, however, only in group L the improvement was significant (p<0.05). In groups L and M a significant reduction of pain intensity was observed at every stage of treatment (p<0.05). CONCLUSIONS: Although after LLL as well as PMF therapy clinical improvement was observed, the most significant differences were registered after the second series and persisted for up to 6 months in both groups. PMID- 22037176 TI - Predictive models for subtypes of autism spectrum disorder based on single nucleotide polymorphisms and magnetic resonance imaging. AB - PURPOSE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder, of which Asperger syndrome and high-functioning autism are subtypes. Our goal is: 1) to determine whether a diagnostic model based on single-nucleotide polymorphisms (SNPs), brain regional thickness measurements, or brain regional volume measurements can distinguish Asperger syndrome from high-functioning autism; and 2) to compare the SNP, thickness, and volume-based diagnostic models. MATERIAL AND METHODS: Our study included 18 children with ASD: 13 subjects with high functioning autism and 5 subjects with Asperger syndrome. For each child, we obtained 25 SNPs for 8 ASD-related genes; we also computed regional cortical thicknesses and volumes for 66 brain structures, based on structural magnetic resonance (MR) examination. To generate diagnostic models, we employed five machine-learning techniques: decision stump, alternating decision trees, multi class alternating decision trees, logistic model trees, and support vector machines. RESULTS: For SNP-based classification, three decision-tree-based models performed better than the other two machine-learning models. The performance metrics for three decision-tree-based models were similar: decision stump was modestly better than the other two methods, with accuracy = 90%, sensitivity = 0.95 and specificity = 0.75. All thickness and volume-based diagnostic models performed poorly. The SNP-based diagnostic models were superior to those based on thickness and volume. For SNP-based classification, rs878960 in GABRB3 (gamma aminobutyric acid A receptor, beta 3) was selected by all tree-based models. CONCLUSION: Our analysis demonstrated that SNP-based classification was more accurate than morphometry-based classification in ASD subtype classification. Also, we found that one SNP--rs878960 in GABRB3--distinguishes Asperger syndrome from high-functioning autism. PMID- 22037177 TI - Blocking the PI3K/AKT and MEK/ERK signaling pathways can overcome gefitinib resistance in non-small cell lung cancer cell lines. AB - PURPOSE: To investigate the effects of gefitinib (EGFR-TKI), LY294002 (PI3K inhibitor) and U0126 (MEK inhibitor) on proliferation and apoptosis in five non small cell lung cancer (NSCLC) cell lines (PC9, PC9/AB2, H1975, H1299 and A549). METHODS: The inhibitory rates of cells were tested by MTT and apoptosis was detected through flow cytometry when treated with gefitinib, LY294002 and U0126. RESULTS: The sensitivity to gefitinib was different in different cell lines, which was associated with EGFR mutation type. The cells with EGFR mutation were more sensitive than those with EGFR wild-type, except PC9/AB2 cells. LY294002 and U0126 can inhibit cell proliferation and promote apoptosis in all five cell lines. The sensitivity to gefitinib was restored partially in the resistant cell lines by combining gefitinib with LY294002 or U0126. The effects on cell proliferation and apoptosis were stronger in cells with EGFR mutation when PI3K/AKT pathway was blocked, however, for cells with EGFR wild-type, the effects were stronger when the MEK pathway was blocked. When the PI3K and MEK pathways were blocked together, proliferation inhibition and apoptosis level in NSCLC cells was similar to that in cells treated with EGFR TKI. There were some differences according to EGFR mutation type, suggesting that EGFR mutations may result in alterations of downstream signaling pathways. CONCLUSION: The sensitivity of gefitinib resistant cell lines can be restored partially when the two downstream signaling pathways are blocked. However, these cells were still drug resistant, suggesting that the activation of PI3K and MEK pathways is not the only mechanism of EGFR-resistance. PMID- 22037178 TI - Association of the ADRA1A gene and the severity of metabolic abnormalities in patients with schizophrenia. AB - Patients with schizophrenia have a higher risk of developing metabolic abnormalities and their associated diseases. Some studies found that the accumulative number of metabolic syndrome components was associated with the severity of metabolic abnormalities. The purpose of this study was to examine the roles of the ADRA1A, ADRA2A, ADRB3, and 5HT2A genes in the risk of having more severe metabolic abnormalities among patients with schizophrenia. We studied a sample of 232 chronic inpatients with schizophrenia (120 males and 112 females) to explore the associations between the four candidate genes and the severity of metabolic syndrome by accumulative number of the components. Four single nucleotide polymorphisms in the candidate genes were genotyped, including the Arg347Cys in ADRA1A, the C1291G in ADRA2A, the Try64Arg in ADRB3, and the T102C in 5HT2A. An association between the accumulative number of metabolic syndrome components and the ADRA1A gene was found after adjusting age, sex, and other related variables (p-value=0.036). Presence of the Arg347 allele in the ADRA1A gene is a risk factor for having more severe metabolic abnormalities. These findings suggest a medical attention of closely monitoring metabolic risks for schizophrenia patients with high-risk genotypes. PMID- 22037179 TI - Cell cycle regulators interact with pathways that modulate microtubule stability in Saccharomyces cerevisiae. AB - The integrity of mitosis is dependent upon strict regulation of microtubule stability and dynamics. Although much information has been accumulated on regulators of the microtubule cytoskeleton, our knowledge of the specific pathways involved is still limited. Here we designed genetic screens to identify regulators of microtubule stability that are dispensable in the wild type yet become essential under microtubule-disrupting conditions. We found that the transcriptional cofactor Swi6p and activator Swi4p, as well as the G(2)/M specific cyclin Clb2p, are required in a microtubule-destabilizing environment. Swi6p and Swi4p can combine as a transcriptional complex, called the SBF complex (SBF for Swi4/6 cell cycle box [SCB]-binding factor) that is functionally homologous to the metazoan DP1/2-E2F complex and that controls the G(1)/S transition through the genes it regulates. We show that Swi6p's contribution to microtubule stability can be either dependent or independent of the SBF complex. The SBF-dependent pathway requires downregulation of SBF complex levels and may thereby reroute the transcriptional program in favor of greater microtubule stability. This pathway can be triggered by overexpression of Fcp1p, a phosphatase in the general transcription machinery, or by expression of an allele of SWI6 that is associated with reduced transcription from SBF-controlled promoters. The SBF-independent pathway is activated by a constitutively nuclear allele of Swi6p. Our results introduce novel roles in microtubule stability for genes whose participation in the process may be masked under normal conditions yet nonetheless acquire a dominant role when microtubule stability is compromised. PMID- 22037180 TI - Efg1 Controls caspofungin-induced cell aggregation of Candida albicans through the adhesin Als1. AB - Echinocandin drugs such as caspofungin (CASP), micafungin, and anidulafungin inhibit fungal cell wall biogenesis by blocking Fks1-mediated beta-glucan deposition into the cell surface. Candins have become suitable drugs to treat life-threatening diseases caused by several fungal species, including Candida albicans, that are pathogenic for humans. Here, we present the discovery of a novel CASP-induced flocculation phenotype of C. albicans, which formed large cell aggregates in the presence of CASP. High concentrations of sugars such as mannose or glucose inhibit CASP-induced flocculation and improve survival of C. albicans cells exposed to CASP. Notably, exposure of C. albicans cells to CASP triggers Efg1-dependent expression of the adhesin ALS1 and induces invasive growth on agar plates. Indeed, cells lacking either Efg1 or Als1 show strongly diminished CASP induced flocculation, and the absence of Efg1 leads to marked CASP hypersensitivity. On the other hand, CASP-induced invasive growth is enhanced in cells lacking Efg1. Hence, CASP stress drives an Efg1-dependent response, indicating that this multifunctional transcriptional regulator, which is otherwise involved in filamentation, white-to-opaque switching, and virulence, also modulates cell wall remodeling upon CASP challenge. Taken together, our data suggest that CASP-induced cell wall damage activates Efg1 in parallel with the known cell integrity stress signaling pathway to coordinate cell wall remodeling. PMID- 22037181 TI - Structural correlates of cytoplasmic and chloroplast lipid body synthesis in Chlamydomonas reinhardtii and stimulation of lipid body production with acetate boost. AB - Light microscopy and deep-etch electron microscopy were used to visualize triacylglyceride (TAG)-filled lipid bodies (LBs) of the green eukaryotic soil alga Chlamydomonas reinhardtii, a model organism for biodiesel production. Cells growing in nitrogen-replete media contain small cytoplasmic lipid bodies (alpha cyto-LBs) and small chloroplast plastoglobules. When starved for N, beta-cyto-LB formation is massively stimulated. beta-Cyto-LBs are intimately associated with both the endoplasmic reticulum membrane and the outer membrane of the chloroplast envelope, suggesting a model for the active participation of both organelles in beta-cyto-LB biosynthesis and packaging. When sta6 mutant cells, blocked in starch biosynthesis, are N starved, they produce beta-cyto-LBs and also chloroplast LBs (cpst-LBs) that are at least 10 times larger than plastoglobules and eventually engorge the chloroplast stroma. Production of beta-cyto-LBs and cpst-LBs under the conditions we used is dependent on exogenous 20 mM acetate. We propose that the greater TAG yields reported for N-starved sta6 cells can be attributed to the strain's ability to produce cpst-LBs, a capacity that is lost when the mutant is complemented by a STA6 transgene. Provision of a 20 mM acetate "boost" during N starvation generates sta6 cells that become so engorged with LBs at the expense of cytoplasm and most organelles-that they float on water even when centrifuged. This property could be a desirable feature for algal harvesting during biodiesel production. PMID- 22037182 TI - Mechanism of the binding of Z-L-tryptophan and Z-L-phenylalanine to thermolysin and stromelysin-1 in aqueous solutions. AB - The chemical shift of the carboxylate carbon of Z-tryptophan is increased from 179.85 to 182.82 ppm and 182.87 ppm on binding to thermolysin and stromelysin-1 respectively. The chemical shift of Z-phenylalanine is also increased from 179.5 ppm to 182.9 ppm on binding to thermolysin. From pH studies we conclude that the pK(a) of the inhibitor carboxylate group is lowered by at least 1.5 pK(a) units when it binds to either enzyme. The signal at ~183 ppm is no longer observed when the active site zinc atom of thermolysin or stromelysin-1 is replaced by cobalt. We estimate that the distance of the carboxylate carbon of Z-[1-(13)C]-L tryptophan is <=3.71A from the active site cobalt atom of thermolysin. We conclude that the side chain of Z-[1-(13)C]-L-tryptophan is not bound in the S(2)' subsite of thermolysin. As the chemical shifts of the carboxylate carbons of the bound inhibitors are all ~183 ppm we conclude that they are all bound in a similar way most probably with the inhibitor carboxylate group directly coordinated to the active site zinc atom. Our spectrophotometric results confirm that the active site zinc atom is tetrahedrally coordinated when the inhibitors Z tryptophan or Z-phenylalanine are bound to thermolysin. PMID- 22037183 TI - Differences in folate-protein interactions result in differing inhibition of native rat liver and recombinant glycine N-methyltransferase by 5 methyltetrahydrofolate. AB - Glycine N-methyltransferase (GNMT) is a key regulatory enzyme in methyl group metabolism. In mammalian liver it reduces S-adenosylmethionine levels by using it to methylate glycine, producing N-methylglycine (sarcosine) and S adenosylhomocysteine. GNMT is inhibited by binding two molecules of 5 methyltetrahydrofolate (mono- or polyglutamate forms) per tetramer of the active enzyme. Inhibition is sensitive to the status of the N-terminal valine of GNMT and to polyglutamation of the folate inhibitor. It is inhibited by pentaglutamate form more efficiently compared to monoglutamate form. The native rat liver GNMT contains an acetylated N-terminal valine and is inhibited much more efficiently compared to the recombinant protein expressed in E. coli where the N-terminus is not acetylated. In this work we used a protein crystallography approach to evaluate the structural basis for these differences. We show that in the folate GNMT complexes with the native enzyme, two folate molecules establish three and four hydrogen bonds with the protein. In the folate-recombinant GNMT complex only one hydrogen bond is established. This difference results in more effective inhibition by folate of the native liver GNMT activity compared to the recombinant enzyme. PMID- 22037184 TI - Phosphodiesterases and subcellular compartmentalized cAMP signaling in the cardiovascular system. AB - Phosphodiesterases are key enzymes in the cAMP signaling cascade. They convert cAMP in its inactive form 5'-AMP and critically regulate the intensity and the duration of cAMP-mediated signals. Multiple isoforms exist that possess different intracellular distributions, different affinities for cAMP, and different catalytic and regulatory properties. This complex repertoire of enzymes provides a multiplicity of ways to modulate cAMP levels, to integrate more signaling pathways, and to respond to the specific needs of the cell within distinct subcellular domains. In this review we summarize key findings on phosphodiesterase compartmentalization in the cardiovascular system. PMID- 22037185 TI - Isolation, bulk cultivation, and characterization of coronary microvascular pericytes: the second most frequent myocardial cell type in vitro. AB - Densely arranged pericytes engird the endothelial tube of all coronary microvessels. Since the experimental access to these abundant cells in situ is difficult, a prerequisite for broader investigation is the availability of sufficient numbers of fully differentiated pericytes in homogenous culture. To reach this goal, we applied strictly standardized cell isolation techniques, optimized culture methods and specific histological staining. Approximately 1,000 fold enriched pericytes were proteolytically detached from highly purified coronary microvascular networks (density gradient centrifugation) of eight mammalian species including human. Addition of species-autologous fetal or neonatal serum (10-20% vol/vol) was a precondition for longer term survival of homogenous pericyte cultures. This ensured optimal growth (doubling time <14 h) and full expression of pericyte-specific markers. In 3-mo, 10(10) pericytes (15 g) could be cultivated from 1 bovine heart. Pericytes could be stored in liquid N(2), recultured, and passaged repeatedly without loss of typical features. In cocultures with EC or vascular smooth muscle cells, pericytes transferred fluorescent calcein to each other and to EC via their antler-like extensions, organized angiogenetic sprouting of vessels, and rapidly activated coagulation factors X and II via tissue factor and prothrombinase. The interconnected pericytes of the coronary system are functionally closely correlated with the vascular endothelium and may play key roles in the adjustment of local blood flow, the regulation of angiogenic processes, and the induction of procoagulatory processes. Their successful bulk cultivation enables direct experimental access under defined in vitro conditions and the isolation of pericyte specific antigens for the production of specific antibodies. PMID- 22037186 TI - Calcium homeostasis in vascular smooth muscle cells is altered in type 2 diabetes by Bcl-2 protein modulation of InsP3R calcium release channels. AB - This study examines the extent to which the antiapoptotic Bcl-2 proteins Bcl-2 and Bcl-x(L) contribute to diabetic Ca(2+) dysregulation and vessel contractility in vascular smooth muscle cells (VSMCs) through their interaction with inositol 1,4,5-trisphosphate receptor (InsP(3)R) intracellular Ca(2+) release channels. Measurements of intracellular ([Ca(2+)](i)) and sarcoplasmic reticulum ([Ca(2+)](SR)) calcium concentrations were made in primary cells isolated from diabetic (db/db) and nondiabetic (db/m) mice. In addition, [Ca(2+)](i) and constriction were recorded simultaneously in isolated intact arteries. Protein expression levels of Bcl-x(L) but not Bcl-2 were elevated in VSMCs isolated from db/db compared with db/m age-matched controls. In single cells, InsP(3)-evoked [Ca(2+)](i) signaling was enhanced in VSMCs from db/db mice compared with db/m. This was attributed to alterations in the intrinsic properties of the InsP(3)R itself because there were no differences between db/db and db/m in the steady state [Ca(2+)](SR) or InsP(3)R expression levels. Moreover, in permeabilized cells the rate of InsP(3)R-dependent SR Ca(2+) release was increased in db/db compared with db/m VSMCs. The enhanced InsP(3)-dependent SR Ca(2+) release was attenuated by the Bcl-2 protein inhibitor ABT-737 only in diabetic cells. Application of ABT-737 similarly attenuated enhanced agonist-induced [Ca(2+)](i) signaling only in intact aortic and mesenteric db/db vessels. In contrast, ABT 737 had no effect on agonist-evoked contractility in either db/db or db/m vessels. Taken together, the data suggest that in type 2 diabetes the mechanism for [Ca(2+)](i) dysregulation in VSMCs involves Bcl-2 protein-dependent increases in InsP(3)R excitability and that dysregulated [Ca(2+)](i) signaling does not appear to contribute to increased vessel reactivity. PMID- 22037187 TI - Contribution of myocardium overlying the anterolateral papillary muscle to left ventricular deformation. AB - Previous studies of transmural left ventricular (LV) strains suggested that the myocardium overlying the papillary muscle displays decreased deformation relative to the anterior LV free wall or significant regional heterogeneity. These comparisons, however, were made using different hearts. We sought to extend these studies by examining three equatorial LV regions in the same heart during the same heartbeat. Therefore, deformation was analyzed from transmural beadsets placed in the equatorial LV myocardium overlying the anterolateral papillary muscle (PAP), as well as adjacent equatorial LV regions located more anteriorly (ANT) and laterally (LAT). We found that the magnitudes of LAT normal longitudinal and radial strains, as well as major principal strains, were less than ANT, while those of PAP were intermediate. Subepicardial and midwall myofiber angles of LAT, PAP, and ANT were not significantly different, but PAP subendocardial myofiber angles were significantly higher (more longitudinal as opposed to circumferential orientation). Subepicardial and midwall myofiber strains of ANT, PAP, and LAT were not significantly different, but PAP subendocardial myofiber strains were less. Transmural gradients in circumferential and radial normal strains, and major principal strains, were observed in each region. The two main findings of this study were as follows: 1) PAP strains are largely consistent with adjacent LV equatorial free wall regions, and 2) there is a gradient of strains across the anterolateral equatorial left ventricle despite similarities in myofiber angles and strains. These findings point to graduated equatorial LV heterogeneity and suggest that regional differences in myofiber coupling may constitute the basis for such heterogeneity. PMID- 22037188 TI - The story so far: post-translational regulation of peroxisome proliferator activated receptors by ubiquitination and SUMOylation. AB - Many studies have implicated the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptor transcription factors in regulating cardiac substrate metabolism and ATP generation. Recently, evidence from a variety of cell culture and organ systems has implicated ubiquitin and small ubiquitin-like modifier (SUMO) conjugation as post-translational modifications that regulate the activity of PPAR transcription factors and their coreceptors/coactivators. Here we introduce the ubiquitin and SUMO conjugation systems and extensively review how they have been shown to regulate all three PPAR isoforms (PPARalpha, PPARbeta/delta, and PPARgamma) in addition to the retinoid X receptor and PPARgamma coactivator-1alpha subunits of the larger PPAR transcription factor complex. We then present how the specific ubiquitin (E3) ligases have been implicated and review emerging evidence that post-translational modifications of PPARs with ubiquitin and/or SUMO may play a role in cardiac disease. Because PPAR activity is perturbed in a variety of forms of heart disease and specific proteins regulate this process (E3 ligases), this may be a fruitful area of investigation with respect to finding new therapeutic targets. PMID- 22037189 TI - Regional skeletal muscle remodeling and mitochondrial dysfunction in right ventricular heart failure. AB - Exercise intolerance is a cardinal symptom of right ventricular heart failure (RV HF) and skeletal muscle adaptations play a role in this limitation. We determined regional remodeling of muscle structure and mitochondrial function in a rat model of RV HF induced by monocrotaline injection (MCT; 60 mg.kg(-1); n = 11). Serial sections of the plantaris were stained for fiber type, succinate dehydrogenase (SDH) activity and capillaries. Mitochondrial function was assessed in permeabilized fibers using respirometry, and isolated complex activity by blue native gel electrophoresis (BN PAGE). All measurements were compared with saline injected control animals (CON; n = 12). Overall fiber cross-sectional area was smaller in MCT than CON: 1,843 +/- 114 vs. 2,322 +/- 120 MUm(2) (P = 0.009). Capillary-to-fiber ratio was lower in MCT in the oxidative plantaris region (1.65 +/- 0.09 vs. 1.93 +/- 0.07; P = 0.03), but not in the glycolytic region. SDH activity (P = 0.048) and maximal respiratory rate (P = 0.012) were each ~15% lower in all fibers in MCT. ADP sensitivity was reduced in both skeletal muscle regions in MCT (P = 0.032), but normalized by rotenone. A 20% lower complex I/IV activity in MCT was confirmed by BN PAGE. MCT-treatment was associated with lower mitochondrial volume density (lower SDH activity), quality (lower complex I activity), and fewer capillaries per fiber area in oxidative skeletal muscle. These features are consistent with structural and functional remodeling of the determinants of oxygen supply potential and utilization that may contribute to exercise intolerance and reduced quality of life in patients with RV HF. PMID- 22037190 TI - Incoherent oscillations of respiratory sinus arrhythmia during acute mental stress in humans. AB - Respiratory sinus arrhythmia (RSA) has been widely used as a measure of the cardiac vagal control in response to stress. However, RSA seems not to be a generalized indicator because of its dependency on respiratory parameter and individual variations of RSA amplitude (A(RSA)). We hypothesized that phase-lag variations between RSA and respiration may serve as a normalized index of the degree of mental stress. Twenty healthy volunteers performed mental arithmetic task (ART) after 5 min of resting control followed by 5 min of recovery. Breathing pattern, beat-to-beat R-R intervals, and blood pressure (BP) were determined using inductance plethysmography, electrocardiography, and a Finapres device, respectively. The analytic signals of breathing and RSA were obtained by Hilbert transform and the degree of phase synchronization (lambda) was quantified. With the use of spectral analysis, heart rate variability (HRV) was estimated for the low-frequency (LF) and high-frequency (HF) bands. A steady state 3-min resting period (REST), the first 3 min (ART1), and the last 3 min (ART2) of the ART period (ranged from 6- to 19 min) and the last 3 min of the recovery period (RCV) were analyzed separately. Heart rate, systolic BP, and breathing frequency (f(R)) increased and lambda, A(RSA), and HF power decreased from REST to ART (P < 0.01). The lambda was correlated with normalized A(RSA) and the HF power. The decrease in lambda could not be explained solely by the increase in f(R). We conclude that mental stress exerts an influence on RSA oscillations, inducing incoherent phase lag with respect to breathing, in addition to a decrease in RSA. PMID- 22037191 TI - p21-activated kinase improves cardiac contractility during ischemia-reperfusion concomitant with changes in troponin-T and myosin light chain 2 phosphorylation. AB - p21-activated kinase 1 (Pak1) is a serine/threonine kinase that activates protein phosphatase 2a, resulting in the dephosphorylation of cardiac proteins and increased myofilament Ca(2+) sensitivity. Emerging evidence indirectly indicates a role for Pak1 in ischemia-reperfusion (I/R), but direct evidence is lacking. We hypothesize that activation of the Pak1 signaling pathway is a cardioprotective mechanism that prevents or reverses the detrimental effects of ischemic injury by inducing posttranslational modifications in myofilament proteins that ultimately improve cardiac contractility following ischemic insult. In the present study, we subjected ex vivo hearts from wild-type (WT) and Pak1-knockout (KO) mice to 20 min of global cardiac ischemia followed by 30 min of reperfusion. In the absence of Pak1, there was an exacerbation of the increased end-diastolic pressure and reduced left ventricular developed pressure occurring after I/R injury. ProQ analysis revealed an increase in troponin-T phosphorylation at baseline in Pak1 KO hearts compared with WT. Significantly decreased myosin light chain 2 (MLC2) phosphorylation in Pak1-KO hearts compared with WT after I/R injury was confirmed by Western immunoblotting. These data indicate that Pak1-KO hearts have reduced recovery of myocardial performance after global I/R injury concomitant with changes in troponin-T and MLC2 phosphorylation. Finally, a protein-protein association between Pak1 and MLC2, and Pak1 and troponin-T, was determined by coimmunoprecipitation. Thus, results of our study provide a basis for targeting a novel pathway, including Pak1, in the therapies for patients with ischemic events. PMID- 22037192 TI - The role of dynamic instability and wavelength in arrhythmia maintenance as revealed by panoramic imaging with blebbistatin vs. 2,3-butanedione monoxime. AB - Unlike other excitation-contraction uncouplers, blebbistatin has few electrophysiological side effects and has gained increasing acceptance as an excitation-contraction uncoupler in optical mapping experiments. However, the possible role of blebbistatin in ventricular arrhythmia has hitherto been unknown. Furthermore, experiments with blebbistatin and 2,3-butanedione monoxime (BDM) offer an opportunity to assess the contribution of dynamic instability and wavelength of impulse propagation to the induction and maintenance of ventricular arrhythmia. Recordings of monophasic action potentials were used to assess effects of blebbistatin in Langendorff-perfused rabbit hearts (n = 5). Additionally, panoramic optical mapping experiments were conducted in rabbit hearts (n = 7) that were sequentially perfused with BDM, then washed out, and subsequently perfused with blebbistatin. The susceptibility to arrhythmia was investigated using a shock-on-T protocol. We found that 1) application of blebbistatin did not change action potential duration (APD) restitution; 2) in contrast to blebbistatin, BDM flattened APD restitution curve and reduced the wavelength; and 3) incidence of sustained arrhythmia was much lower under blebbistatin than under BDM (2/123 vs. 23/99). While arrhythmias under BDM were able to stabilize, the arrhythmias under blebbistatin were unstable and terminated spontaneously. In conclusion, the lower susceptibility to arrhythmia under blebbistatin than under BDM indicates that blebbistatin has less effects on arrhythmia dynamics. A steep restitution slope under blebbistatin is associated with higher dynamic instability, manifested by the higher incidence of not only wave breaks but also wave extinctions. This relatively high dynamic instability leads to the self-termination of arrhythmia because of the sufficiently long wavelength under blebbistatin. PMID- 22037193 TI - Optical mapping of cryoinjured rat myocardium grafted with mesenchymal stem cells. AB - Mesenchymal stem cells (MSCs) have been shown to improve cardiac electrophysiology when administered in the setting of acute myocardial infarction. However, the electrophysiological phenotype of MSCs in situ is not clear. We hypothesize that MSCs delivered intramyocardially to cryoinjured myocardium can engraft, but will not actively generate, action potentials. Cryoinjury-induced scar was created on the left ventricular epicardial surface of adult rat hearts. Within 30 min, hearts were injected with saline (sham, n = 11) or bone marrow-derived MSCs (2 * 10(6)) labeled with 1,1'-dioctadecyl-3,3,3,3' tetramethylindocarbocyanine percholate (DiI; n = 16). At 3 wk, optical mapping and cell isolation were used to measure optical action potentials and calcium transients, respectively. Histological analysis confirmed subepicardial scar thickness and the presence of DiI-positive cells that express connexin-43. Optical action potential amplitude within the scar at MSC-positive sites (53.8 +/ 14.3%) was larger compared with sites devoid of MSCs (35.3 +/- 14.2%, P < 0.05) and sites within the scar of shams (33.5 +/- 6.9%, P < 0.05). Evidence of simultaneous action potential upstroke, the loss of action potential activity following ablation of adjacent viable myocardium, and no rapid calcium transient response in isolated DiI+ cells suggest that the electrophysiological influence of engrafted MSCs is electrotonic. MSCs can engraft when directly injected into a cryoinjury and are associated with evidence of action potential activity. However, our results suggest that this activity is not due to generation of action potentials, but rather passive influence coupled from neighboring viable myocardium. PMID- 22037194 TI - Effects of cyclooxygenase inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. AB - The cardiovascular effects of cyclooxygenase (COX) inhibition remain controversial, especially in the setting of cardiovascular comorbidities. We examined the effects of nonselective and selective COX inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. Twenty-four intact male Yorkshire swine underwent left circumflex ameroid constrictor placement and were subsequently given either no drug (HCC; n = 8), a nonselective COX inhibitor (440 mg/day naproxen; HCNS; n = 8), or a selective COX-2 inhibitor (200 mg/day celecoxib; HCCX; n = 8). After 7 wk, myocardial functional was measured and myocardium from the nonischemic ventricle and ischemic area-at-risk (AAR) were analyzed. Regional function as measured by segmental shortening was improved in the AAR of HCCX compared with HCC. There was no significant difference in perfusion to the nonischemic ventricle between groups, but myocardial perfusion in the AAR was significantly improved in the HCCX group compared with controls at rest and during pacing. Endothelium dependent microvessel relaxation was diminished by ischemia in HCC animals, but both naproxen and celecoxib improved vessel relaxation in the AAR compared with controls, and also decreased the vasoconstrictive response to serotonin. Thromboxane levels in the AAR were decreased in both HCNS and HCCX compared with HCC, whereas prostacyclin levels were decreased only in HCNS, corresponding to a decrease in prostacyclin synthase expression. Chronic ischemia increased apoptosis in Troponin T negative cells and intramyocardial fibrosis, both of which were reduced by celecoxib administration in the AAR. Capillary density was decreased in both the HCNS and HCCX groups. Protein oxidative stress was decreased in both HCNS and HCCX, whereas lipid oxidative stress was decreased only in the HCCX group. Thus nonselective and especially selective COX inhibition may have beneficial myocardial effects in the setting of hypercholesterolemia and chronic ischemia. Whether these effects modulate cardiovascular risk in patients taking these drugs remains to be seen, but evidence to date suggests that they do not. PMID- 22037196 TI - Spectrographic analyses reveal signals of individuality and kinship in the ultrasonic courtship vocalizations of wild house mice. AB - Male house mice produce ultrasonic vocalizations (USVs) during courtship; however, it is unclear why males produce USVs and what information their calls communicate. In laboratory mice, male USVs are attractive to females [1,2]. They appear to facilitate mating and coordinate copulation behavior [3,4] perhaps because USVs provide information about males' quality or compatibility. In our studies on wild house mice (Mus musculus musculus), we found that females can discriminate the USVs of unrelated males versus siblings [5]. In this study we conducted spectrographic and temporal analyses on recordings of courtship USVs of wild males. We found evidence that males' vocalizations contain signatures of individuality and kinship. The individuality of males' USVs could be due to differences in the filter function of the vocal tract or differences of the vocal apparatus, which might directly influence the temporal and spectral features of vocalizations. Further studies are needed to determine the consistency of individual USVs over longer periods of time and across contexts, and whether the familial effects we found are due to genetic relatedness, social learning (imprinting), or both. PMID- 22037195 TI - Cardiomyocyte deletion of mitofusin-1 leads to mitochondrial fragmentation and improves tolerance to ROS-induced mitochondrial dysfunction and cell death. AB - Molecular studies examining the impact of mitochondrial morphology on the mammalian heart have previously focused on dynamin related protein-1 (Drp-1) and mitofusin-2 (Mfn-2), while the role of the other mitofusin isoform, Mfn-1, has remained largely unexplored. In the present study, we report the generation and initial characterization of cardiomyocyte-specific Mfn-1 knockout (Mfn-1 KO) mice. Using electron microscopic analysis, we detect a greater prevalence of small, spherical mitochondria in Mfn-1 KO hearts, indicating that the absence of Mfn-1 causes a profound shift in the mitochondrial fusion/fission balance. Nevertheless, Mfn-1 KO mice exhibit normal left-ventricular function, and isolated Mfn-1 KO heart mitochondria display a normal respiratory repertoire. Mfn 1 KO myocytes are protected from mitochondrial depolarization and exhibit improved viability when challenged with reactive oxygen species (ROS) in the form of hydrogen peroxide (H(2)O(2)). Furthermore, in vitro studies detect a blunted response of KO mitochondria to undergo peroxide-induced mitochondrial permeability transition pore opening. These data suggest that Mfn-1 deletion confers protection against ROS-induced mitochondrial dysfunction. Collectively, we suggest that mitochondrial fragmentation in myocytes is not sufficient to induce heart dysfunction or trigger cardiomyocyte death. Additionally, our data suggest that endogenous levels of Mfn-1 can attenuate myocyte viability in the face of an imminent ROS overload, an effect that could be associated with the ability of Mfn-1 to remodel the outer mitochondrial membrane. PMID- 22037197 TI - Behavioural and physiological effects of population density on domesticated Zebra Finches (Taeniopygia guttata) held in aviaries. AB - Zebra Finches (Taeniopygia guttata) are highly social and monogamous birds that display relatively low levels of aggression and coordinate group life mainly by means of vocal communication. In the wild, small groups may congregate to larger flocks of up to 150-350 birds. Little is known, however, about possible effects of population density on development in captivity. Investigating density effects on physiology and behaviour might be helpful in identifying optimal group size, in order to optimise Zebra Finch wellbeing. A direct effect of population density on development and reproduction was found: birds in lower density conditions produced significantly more and larger (body mass, tarsus length) surviving offspring than birds in high density conditions. Furthermore, offspring in low density aviaries produced slightly longer song motifs and more different syllables than their tutors, whereas offspring in high density aviaries produced shorter motifs and a smaller or similar number of different syllables than their tutors. Aggression levels within the populations were low throughout the experiment, but the number of aggressive interactions was significantly higher in high density aviaries. Baseline corticosterone levels did not differ significantly between high- and low density aviaries for either adult or offspring birds. On day 15 post hatching, brood size and baseline corticosterone levels were positively correlated. On days 60 and 100 post hatching this correlation was no longer present. The results of this study prove that population density affects various aspects of Zebra Finch development, with birds living in low population density conditions having an advantage over those living under higher population density conditions. PMID- 22037198 TI - Prenatal stress produces sex differences in nest odor preference. AB - Prenatal stress (PS) and early postnatal environment may alter maternal care. Infant rats learn to identify their mother through the association between maternal care and familiar odors. Female Wistar rats were exposed to restraint stress for 30 min, 4 sessions per day, in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatal non stressed mothers raising non-stressed pups (NS:NS), prenatal stressed mothers raising non-stressed pups (S:NS), prenatal non-stressed mothers raising stressed pups (NS:S), prenatal stressed mothers raising stressed pups (S:S). Maternal behaviors were assessed during 6 postpartum days. On postnatal day (PND) 7, the behavior of male and female pups was analyzed in the odor preference test; and noradrenaline (NA) activity in olfactory bulb (OB) was measured. The results showed that restraint stress increased plasma levels of corticosterone on gestational day 15. After parturition, PS reduced maternal care, decreasing licking the pups and increasing frequency outside the nest. Female pups from the NS:S, S:NS, S:S groups and male pups from the S:S group showed no nest odor preference. Thus, at day 7, female pups that were submitted to perinatal interventions showed more impairment in the nest odor preference test than male pups. No changes were detected in the NA activity in the OB. In conclusion, repeated restraint stress during the last week of gestation reduces maternal care and reduces preference for a familiar odor in rat pups in a sex-specific manner. PMID- 22037199 TI - Posttransplant sCD30 as a biomarker to predict kidney graft outcome. AB - In current clinical praxis, monitoring of immunosuppressive agents in organ transplantation is restricted to measurement of drug blood levels and does not consider the drug's variable effect on the individual patient's immune system. Establishment of biological markers that measure the biological effect of immunosuppressive drugs is desirable and would enable the identification of patients who are at risk of developing rejection, or patients who are suitable for minimization or weaning of immunosuppressive therapy. Several studies demonstrated that the technically simple posttransplant measurement in serum of the T cell activation marker soluble CD30 (sCD30) allows prediction of subsequent graft loss in kidney transplant recipients. sCD30 is a relatively large molecule and therefore an attractive biological marker which is resistant to repeated thawing cycles and temperature differences and easily determined using commercial ELISA. Whether sCD30-based prospective adjustment of immunosuppressive therapy can prevent irreversible graft damage and improve long-term graft outcome awaits evaluation in randomized controlled trials. PMID- 22037200 TI - Infestation of Mauritia flexuosa palms by triatomines (Hemiptera: Reduviidae), vectors of Trypanosoma cruzi and Trypanosoma rangeli in the Brazilian savanna. AB - To determine the infestation and trypanosome infection of triatomines captured in Mauritia flexuosa palm trees across its geographic distribution in the Brazilian savanna (Cerrado), we sampled 42 localities in eight states and in the Federal District, Brazil, between July 2005 and January 2010. Overall, 2154 specimens of the species Rhodnius neglectus, Psammolestes tertius, Triatoma sordida, and Microtriatoma borbai, were collected. Among the 341 palms sampled, 182 (53.3%) were infested with R. neglectus, which resulted in the capture of 1639 specimens (9.0 insects per infested palm). P. tertius occurred in 26 palms (8%), which resulted in the capture of 484 specimens (19 insects per infested palm). T. sordida (n=30) and M. borbai (n=1) occurred in only one location. From 537 R. neglectus examined, 44 were infected (8%) with Trypanosoma rangeli and/or Trypanosoma cruzi (Tc Id). M. flexuosa was previously recognized as a suitable breeding ecotope for R. neglectus in the Brazilian states of Minas Gerais, Goias, Tocantins and the Federal District. Our results expand this distribution to other states (Sao Paulo, Bahia, Mato Grosso, Maranhao and Piaui), and also show that this particular palm tree harbors other triatomine species. Finally, we show that R. neglectus plays an important role in maintaining the enzootic circulation of T. cruzi and T. rangeli in the Brazilian savanna. PMID- 22037201 TI - Characterization of two mutations, M287L and Q266I, in the alpha1 glycine receptor subunit that modify sensitivity to alcohols. AB - Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels. Ethanol potentiates glycine activation of the GlyR, and putative binding sites for alcohol are located in the transmembrane (TM) domains between and within subunits. To alter alcohol sensitivity of GlyR, we introduced two mutations in the GlyR alpha1 subunit, M287L (TM3) and Q266I (TM2). After expression in Xenopus laevis oocytes, both mutants showed a reduction in glycine sensitivity and glycine-induced maximal currents. Activation by taurine, another endogenous agonist, was almost abolished in the M287L GlyR. The ethanol potentiation of glycine currents was reduced in the M287L GlyR and eliminated in Q266I. Physiological levels of zinc (100 nM) potentiate glycine responses in wild-type GlyR and also enhance the ethanol potentiation of glycine responses. Although zinc potentiation of glycine responses was unchanged in both mutants, zinc enhancement of ethanol potentiation of glycine responses was absent in M287L GlyRs. The Q266I mutation decreased conductance but increased mean open time (effects not seen in M287L). Two lines of knockin mice bearing these mutations were developed. Survival of homozygous knockin mice was impaired, probably as a consequence of impaired glycinergic transmission. Glycine showed a decreased capacity for displacing strychnine binding in heterozygous knockin mice. Electrophysiology in isolated neurons of brain stem showed decreased glycine mediated currents and decreased ethanol potentiation in homozygous knockin mice. Molecular models of the wild-type and mutant GlyRs show a smaller water-filled cavity within the TM domains of the Q266I alpha1 subunit. The behavioral characterization of these knockin mice is presented in a companion article (J Pharmacol Exp Ther 340:317-329, 2012). PMID- 22037202 TI - Behavioral characterization of knockin mice with mutations M287L and Q266I in the glycine receptor alpha1 subunit. AB - We used behavioral pharmacology to characterize heterozygous knockin mice with mutations (Q266I or M287L) in the alpha1 subunit of the glycine receptor (GlyR) (J Pharmacol Exp Ther 340:304-316, 2012). These mutations were designed to reduce (M287L) or eliminate (Q266I) ethanol potentiation of GlyR function. We asked which behavioral effects of ethanol would be reduced more in the Q266I mutant than the M287L and found rotarod ataxia to be the behavior that fulfilled this criterion. Compared with controls, the mutant mice also differed in ethanol consumption, ethanol-stimulated startle response, signs of acute physical dependence, and duration of loss of righting response produced by ethanol, butanol, ketamine, pentobarbital, and flurazepam. Some of these behavioral changes were mimicked in wild-type mice by acute injections of low, subconvulsive doses of strychnine. Both mutants showed increased acoustic startle response and increased sensitivity to strychnine seizures. Thus, in addition to reducing ethanol action on the GlyRs, these mutations reduced glycinergic inhibition, which may also alter sensitivity to GABAergic drugs. PMID- 22037203 TI - Behavioral characterization of the alarm reaction and anxiolytic-like effect of acute treatment with fluoxetine in piaucu fish. AB - In Ostariophysan fish, the detection of the alarm substance liberated into the water as a consequence of an attack by a predator elicits an alarm reaction or anti-predatory behavior. In this study, experiments were performed to: (i) describe and quantitatively characterize the behavioral and ventilatory responses in piaucu fish (Leporinus macrocephalus), individually and as part of a school, to conspecific alarm substance (CAS) and; (ii) test the effect of acute fluoxetine treatment on alarm reaction. Histological analysis revealed the presence of club cells in the intermediate and superficial layers of the epidermis. The predominant behavioral response to CAS was freezing for fish held individually, characterized by the cessation of the swimming activity as the animal settles to a bottom corner of the aquarium. Fish exposed to CAS showed decrease in the mean ventilatory frequency (approximately 13%) relative to control. In schools, CAS elicited a biphasic response that was characterized by erratic movements followed by increased school cohesion and immobility, reflected as an increased school cohesion (65.5% vs. -5.8% for controls) and in the number of animals near the bottom of the aquarium (42.0% vs. 6.5% for controls). Animals treated with single i.p. injections of fluoxetine (10 MUg/g b.w.) did not exhibit alarm behavior following CAS stimulation. These results show that an alarm pheromone system is present in piaucu fish, evidenced by the presence of epidermal club cells and an alarm reaction induced by CAS and consequently of a chemosensory system to transmit the appropriate information to neural structures responsible for initiating anti-predator behavioral responses. In addition, fluoxetine treatment caused an anxiolytic-like effect following CAS exposure. Thus, the alarm reaction in piaucu can be a useful model for neuroethological and pharmacological studies of anxiety-related states. PMID- 22037205 TI - Epilepsy awareness in a Jamaican community: driven to change! AB - There are relatively few published studies on epilepsy-related knowledge, attitudes, and practices (KAP) from developing countries and none from Jamaica. A questionnaire-based, cross-sectional study of 320 individuals was performed in a small community in Kingston. Residents and employees were comparable in age, sex, and personal and family history of epilepsy, but differed in attained education and occupation. Persons with postsecondary education were less likely to believe that epilepsy is a mental disorder (9% vs 24.8%, P<0.001), is due to demonic possession (8% vs 18.2%, P<0.01), or is contagious (2.5% vs 23%, P<0.001). Overall, 73% felt that people with epilepsy should not drive. The results of this Jamaican KAP study differ from those in other developing countries. There appears to be less societal stigma in Jamaica; however, there is widespread reluctance to allow PWE to drive. This represents a substantial challenge to the current initiative to change existing driving regulations that currently bar people with epilepsy from driving. PMID- 22037204 TI - Vaccine induced antibodies to the first variable loop of human immunodeficiency virus type 1 gp120, mediate antibody-dependent virus inhibition in macaques. AB - The role of antibodies directed against the hyper variable envelope region V1 of human immunodeficiency virus type 1 (HIV-1), has not been thoroughly studied. We show that a vaccine able to elicit strain-specific non-neutralizing antibodies to this region of gp120 is associated with control of highly pathogenic chimeric SHIV(89.6P) replication in rhesus macaques. The vaccinated animal that had the highest titers of antibodies to the amino terminus portion of V1, prior to challenge, had secondary antibody responses that mediated cell killing by antibody-dependent cellular cytotoxicity (ADCC), as early as 2 weeks after infection and inhibited viral replication by antibody-dependent cell-mediated virus inhibition (ADCVI), by 4 weeks after infection. There was a significant inverse correlation between virus level and binding antibody titers to the envelope protein, (R=-0.83, p=0.015), and ADCVI (R=-0.84 p=0.044). Genotyping of plasma virus demonstrated in vivo selection of three SHIV(89.6P) variants with changes in potential N-linked glycosylation sites in V1. We found a significant inverse correlation between virus levels and titers of antibodies that mediated ADCVI against all the identified V1 virus variants. A significant inverse correlation was also found between neutralizing antibody titers to SHIV(89.6) and virus levels (R=-0.72 p=0.0050). However, passive inoculation of purified immunoglobulin from animal M316, the macaque that best controlled virus, to a naive macaque, resulted in a low serum neutralizing antibodies and low ADCVI activity that failed to protect from SHIV(89.6P) challenge. Collectively, while our data suggest that anti-envelope antibodies with neutralizing and non neutralizing Fc(R-dependent activities may be important in the control of SHIV replication, they also demonstrate that low levels of these antibodies alone are not sufficient to protect from infection. PMID- 22037206 TI - Comparison of gamma-ray coincidence and low-background gamma-ray singles spectrometry. AB - Aerosol samples have been studied under different background conditions using gamma-ray coincidence and low-background gamma-ray singles spectrometric techniques with High-Purity Germanium detectors. Conventional low-background gamma-ray singles counting is a competitive technique when compared to the gamma gamma coincidence approach in elevated background conditions. However, measurement of gamma-gamma coincidences can clearly make the identification of different nuclides more reliable and efficient than using singles spectrometry alone. The optimum solution would be a low-background counting station capable of both singles and gamma-gamma coincidence spectrometry. PMID- 22037208 TI - A few good genes: simple, biologically motivated signatures for cancer prognosis. PMID- 22037207 TI - SOX10 regulates expression of the SH3-domain kinase binding protein 1 (Sh3kbp1) locus in Schwann cells via an alternative promoter. AB - The transcription factor SOX10 has essential roles in neural crest-derived cell populations, including myelinating Schwann cells-specialized glial cells responsible for ensheathing axons in the peripheral nervous system. Importantly, SOX10 directly regulates the expression of genes essential for proper myelin function. To date, only a handful of SOX10 target loci have been characterized in Schwann cells. Addressing this lack of knowledge will provide a better understanding of Schwann cell biology and candidate loci for relevant diseases such as demyelinating peripheral neuropathies. We have identified a highly conserved SOX10 binding site within an alternative promoter at the SH3-domain kinase binding protein 1 (Sh3kbp1) locus. The genomic segment identified at Sh3kbp1 binds to SOX10 and displays strong promoter activity in Schwann cells in vitro and in vivo. Mutation of the SOX10 binding site ablates promoter activity, and ectopic expression of SOX10 in SOX10-negative cells promotes the expression of endogenous Sh3kbp1. Combined, these data reveal Sh3kbp1 as a novel target of SOX10 and raise important questions regarding the function of SH3KBP1 isoforms in Schwann cells. PMID- 22037209 TI - Systems biology of epistasis: shedding light on genetic interaction network "hubs". PMID- 22037210 TI - Polypyrimidine tract-binding protein regulates the cell cycle through IRES dependent translation of CDK11(p58) in mouse embryonic stem cells. AB - Polypyrimidine tract-binding protein (PTB/PTBP1/hnRNP I) is a member of the heterogeneous nuclear ribonucleoprotein family that binds specifically to pyrimidine-rich sequences of RNAs. Although PTB is a multifunctional protein involved in RNA processing and internal ribosome entry site (IRES)-dependent translation, the role of PTB in early mouse development is unclear. Ptb knockout mice exhibit embryonic lethality shortly after implantation and Ptb-/- embryonic stem (ES) cells have a severe proliferation defect that includes a prolonged G2/M phase. The present study shows that PTB promotes M phase progression by the direct repression of CDK11(p58) IRES activity in ES cells. The protein expression and IRES activity of CDK11(p58) in Ptb-/- ES cells is higher than that of wild type ES cells, indicating that PTB is involved in the repression of CDK11(p58) expression through IRES-dependent translation in ES cells. Interestingly, CDK11(p58) IRES activity is activated by upstream of N-Ras (UNR) in 293T and NIH3T3 cells, whereas UNR is not present in the Cdk11 mRNA-protein complex in ES cells. In addition, PTB interacts directly with the IRES region of CDK11(p58) in ES cells. These results suggest that PTB regulates the precise expression of CDK11(p58) through direct interaction with CDK11(p58) IRES and promotes M phase progression in ES cells. PMID- 22037213 TI - Primary cerebral lymphoma with spontaneous remission. PMID- 22037211 TI - Closed MAD2 (C-MAD2) is selectively incorporated into the mitotic checkpoint complex (MCC). AB - The mitotic checkpoint is a specialized signal transduction pathway that monitors kinetochore-microtubule attachment to achieve faithful chromosome segregation. MAD2 is an evolutionarily conserved mitotic checkpoint protein that exists in open (O) and closed (C) conformations. The increase of intracellular C-MAD2 level during mitosis, through O->C-MAD2 conversion as catalyzed by unattached kinetochores, is a critical signaling event for the mitotic checkpoint. However, it remains controversial whether MAD2 is an integral component of the effector of the mitotic checkpoint--the Mitotic Checkpoint Complex (MCC). We show here that endogenous human MCC is assembled by first forming a BUBR1:BUB3:CDC20 complex in G2 and then selectively incorporating C-MAD2 during mitosis. Nevertheless, MCC can be induced to form in G1/S cells by expressing a C-conformation locked MAD2 mutant, indicating intracellular level of C-MAD2 as a major limiting factor for MCC assembly. In addition, a recombinant MCC containing C-MAD2 exhibits effective inhibitory activity towards APC/C isolated from mitotic HeLa cells, while a recombinant BUBR1:BUB3:CDC20 ternary complex is ineffective at comparable concentrations despite association with APC/C. These results help establish a direct connection between a major signal transducer (C-MAD2) and the potent effector (MCC) of the mitotic checkpoint, and provide novel insights into protein protein interactions during assembly of a functional MCC. PMID- 22037214 TI - The apelin/APJ system induces maturation of the tumor vasculature and improves the efficiency of immune therapy. AB - Immature and unstable tumor vasculature provides an aberrant tumor microenvironment and leads to resistance of tumors to conventional therapy. Hence, normalization of tumor vessels has been reported to improve the effect of immuno-, chemo- and radiation therapy. However, the humoral factors, which can effectively induce maturation of tumor vasculature, have not been elucidated. In this study, we found that the novel peptide apelin and its receptor APJ can induce the morphological and functional maturation of blood vessels in tumors. This apelin-induced tumor vascular maturation enhances the efficacy of cancer dendritic cell-based immunotherapy and significantly suppresses tumor growth by promoting the infiltration of invariant natural killer T cells into the central region of the tumor and thereby robustly inducing apoptosis of tumor cells. Additionally, we showed APJ expression to be enhanced in the tumor endothelium in comparison with normal-state endothelial cells. These findings provide a new target for tumor vascular-specific maturation, which is expected to improve the efficacy of conventional cancer therapies. PMID- 22037215 TI - Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia. AB - Women with type 2 diabetes mellitus (T2DM) are at a greater risk of developing and dying from breast cancer than women without T2DM. Insulin resistance and hyperinsulinemia underlie the pathogenesis of T2DM. In the MKR mouse model of insulin resistance, we have previously shown increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in association with accelerated mammary tumor growth. In this study, we demonstrate that inhibiting PI3K with the oral pan-class I PI3K inhibitor, NVP-BKM120 reduced the growth of Met-1 and MCNeuA mammary tumor orthografts in the MKR mouse. NVP-BKM120 treatment decreased phosphorylation of Akt and S6 ribosomal protein (S6rp); no change in Erk1/2 phosphorylation was seen. Hyperglycemia, hypertriglyceridemia and greater hyperinsulinemia developed in the MKR mice treated with NVP-BKM120. We previously reported reduced tumor growth using intraperitoneal rapamycin in the MKR mouse, with the development of hyperglycemia and hypertriglyceridemia. Therefore, we examined whether the oral PI3K/mTOR inhibitor NVP-BEZ235 augmented the tumor suppressing effects of PI3K inhibition. We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia. NVP-BEZ235 suppressed the growth of Met-1 and MCNeuA tumor orthografts, and decreased Akt and S6rp phosphorylation, despite increased Erk1/2 phosphorylation in Met-1 orthografts of MKR mice. Less marked hyperglycemia and hyperinsulinemia developed with NVP-BEZ235 than NVP-BKM120. Overall, the results of this study demonstrated that inhibiting PI3K/Akt/mTOR signaling with the oral agents NVP-BKM120 and NVP-BEZ235 decreased mammary tumor growth in the hyperinsulinemic MKR mouse. Inhibiting PI3K alone led to more severe metabolic derangement than inhibiting both PI3K and mTOR. Therefore, PI3K may be an important target for the treatment of breast cancer in women with insulin resistance. Monitoring for hyperglycemia and dyslipidemia should be considered when using these agents in humans, given the metabolic changes detected in this study. PMID- 22037216 TI - TGF-beta drives epithelial-mesenchymal transition through deltaEF1-mediated downregulation of ESRP. AB - Epithelial-mesenchymal transition (EMT) is a crucial event in wound healing, tissue repair and cancer progression in adult tissues. We have recently shown that transforming growth factor (TGF)-beta-induced EMT involves isoform switching of fibroblast growth factor receptors by alternative splicing. We performed a microarray-based analysis at single exon level to elucidate changes in splicing variants generated during TGF-beta-induced EMT, and found that TGF-beta induces broad alteration of splicing patterns by downregulating epithelial splicing regulatory proteins (ESRPs). This was achieved by TGF-beta-mediated upregulation of deltaEF1 family proteins, deltaEF1 and SIP1. deltaEF1 and SIP1 each remarkably repressed ESRP2 transcription through binding to the ESRP2 promoter in NMuMG cells. Silencing of both deltaEF1 and SIP1, but not either alone, abolished the TGF-beta-induced ESRP repression. The expression profiles of ESRPs were inversely related to those of deltaEF1 and SIP in human breast cancer cell lines and primary tumor specimens. Further, overexpression of ESRPs in TGF-beta-treated cells resulted in restoration of the epithelial splicing profiles as well as attenuation of certain phenotypes of EMT. Therefore, deltaEF1 family proteins repress the expression of ESRPs to regulate alternative splicing during TGF-beta induced EMT and the progression of breast cancers. PMID- 22037217 TI - Loss of TGF-beta signaling and PTEN promotes head and neck squamous cell carcinoma through cellular senescence evasion and cancer-related inflammation. AB - The molecular mechanisms that contribute to the initiation and progression of head and neck squamous cell carcinoma (HNSCC) have not been completely delineated. Our observations indicate that defects in the transforming growth factor-beta and PI3K/Akt signaling pathways are common in human HNSCCs. Conditional activation of the PI3K/Akt pathway due to Pten deletion in the mouse head and neck epithelia gives rise to hyperproliferation, but only a few lesions progress to HNSCC. However, Pten-deficient mice developed full-penetrance HNSCC in combination with type I TGF-beta receptor (Tgfbr1) deletion. Molecular analysis revealed enhanced cell proliferation, decreased apoptosis, and increased expression of CCND1 in the basal layer of the head and neck epithelia, as well as in the tumors of Tgfbr1/Pten double conditional knockout (2cKO) mice. Furthermore, neoplastic transformation involves senescence evasion, and is associated with an increased number of putative cancer stem cells. In addition, the nuclear factor-kappaB pathway activation, myeloid-derived suppressor cell infiltration, angiogenesis and immune suppression in the tumor microenvironment, all of which are characteristics of human HNSCCs, contribute significantly to head and neck carcinogenesis in 2cKO mice. These tumors display pathology and multiple molecular alterations resembling human HNSCCs. This suggests that the Tgfbr1/Pten 2cKO mouse model is suitable for preclinical intervention, and that it has significant implications in the development of diagnostic cancer biomarkers and effective strategies for prevention and treatment of HNSCCs. PMID- 22037219 TI - Advances in management of low-risk febrile neutropenia. AB - PURPOSE OF REVIEW: To describe and discuss the most recent advances in the management of low-risk febrile neutropenia in children with cancer. RECENT FINDINGS: Several risk stratification tools for children with febrile neutropenia have been developed, although none of these tools have been directly compared and few have been validated in independent populations. However, there is good evidence that, for pediatric patients with febrile neutropenia at low risk for severe infection, outpatient management is a well tolerated and efficacious alternative to inpatient care. Moreover, major progress has been made in obtaining and understanding perceived quality of life and preferences for outpatient management in pediatric cancer patients. Many parents prefer inpatient management although child quality of life is, in general, anticipated to be higher with outpatient intravenous therapy. Finally, outpatient strategies are more cost-effective as compared with traditional management in hospital. SUMMARY: Outpatient management is a well tolerated and cost-effective strategy for low risk febrile neutropenia in children with cancer, although parental preferences are highly variable for outpatient versus inpatient management. Future research should examine the effectiveness of outpatient strategies through conduct of large cohort studies. Other future work could focus on development of decision aids and other tools to facilitate ambulatory approaches. PMID- 22037218 TI - Racial differences in the association between carotid plaque and aortic and coronary artery calcification among women transitioning through menopause. AB - OBJECTIVE: Carotid atherosclerosis is a marker for atherosclerotic disease in other vascular beds; however, racial differences in this association have not been fully examined. The purpose of this report was to evaluate racial differences in the relationship between carotid plaque and calcification in the aorta and coronary arteries among women transitioning through menopause. METHODS: A total of 540 African American and white women with a median age of 50 years were evaluated from the Study of Women's Health Across the Nation. Carotid plaque (none vs. any) was assessed with B-mode ultrasound, and aortic calcification (AC; 0, >0-100, and >100) and coronary artery calcification (CAC; 0, >0-10, and >10) were assessed with CT. RESULTS: For the total cohort, higher prevalence of plaque was significantly associated with higher levels of AC but not CAC. The interaction of race and carotid plaque was significant in models with AC and CAC as dependent variables (P = 0.03 and 0.002, respectively). Among African Americans, there was an inverse relationship, although not significant, between carotid plaque and high AC (>100; odds ratio [OR], 0.75; 95% CI, 0.10-5.48) and between plaque and high CAC (>10; OR, 0.20; 95% CI, 0.03-1.52) in fully adjusted models. In contrast, for whites, significant positive associations existed between carotid plaque and high AC (OR, 4.12; 95% CI, 1.29-13.13) and borderline associations for high CAC (OR, 1.83; 95% CI, 0.66-5.19). CONCLUSIONS: This study demonstrates that the presence of carotid plaque seemed to be a marker for AC and potentially CAC in white women, but not African American middle-aged women, during the menopausal transition. PMID- 22037220 TI - Behavioral interventions in children and adolescents with autism spectrum disorder: a review of recent findings. AB - PURPOSE OF REVIEW: The study provides an overview of recent studies on behavioral interventions for children and adolescents with autism spectrum disorder (ASD). RECENT FINDINGS: Recent reviews of the effectiveness of early intensive behavioral intervention (EIBI) conclude that EIBI can improve language and cognitive skills. The first randomized controlled trial (RCT) of a comprehensive early intervention for toddlers with ASD demonstrated gains in language, cognitive abilities, and adaptive behavior. Targeted, brief behavioral interventions are efficacious for improving social communication in young children with ASD. Parents can be taught to deliver behavioral interventions, which are associated with improvements in parent-child interaction; effects on child outcome, however, have been mixed. Several studies show that social skills interventions are efficacious for improving peer relationships and social competence. Behavioral interventions are also effective for reducing anxiety symptoms and aggression. Medication combined with behavioral intervention was found to be more effective for reducing aggression than medication alone. SUMMARY: Behavioral interventions are effective for improving language, cognitive abilities, adaptive behavior, and social skills, and reducing anxiety and aggression. Medication combined with behavioral intervention appears to be more effective for reducing aggressive behavior than medication alone. PMID- 22037221 TI - High-pressure crystal structure of elastically isotropic CaTiO3 perovskite under hydrostatic and non-hydrostatic conditions. AB - The structural evolution of orthorhombic CaTiO3 perovskite has been studied using high-pressure single-crystal x-ray diffraction under hydrostatic conditions up to 8.1 GPa and under a non-hydrostatic stress field formed in a diamond anvil cell (DAC) up to 4.7 GPa. Under hydrostatic conditions, the TiO6 octahedra become more tilted and distorted with increasing pressure, similar to other 2:4 perovskites. Under non-hydrostatic conditions, the experiments do not show any apparent difference in the internal structural variation from hydrostatic conditions and no additional tilts and distortions in the TiO6 octahedra are observed, even though the lattice itself becomes distorted due to the non-hydrostatic stress. The similarity between the hydrostatic and non-hydrostatic cases can be ascribed to the fact that CaTiO3 perovskite is nearly elastically isotropic and, as a consequence, its deviatoric unit-cell volume strain produced by the non hydrostatic stress is very small; in other words, the additional octahedral tilts relevant to the extra unit-cell volume associated with the deviatoric unit-cell volume strain may be totally neglected. This study further addresses the role that three factors--the elastic properties, the crystal orientation and the pressure medium--have on the structural evolution of an orthorhombic perovskite loaded in a DAC under non-hydrostatic conditions. The influence of these factors can be clearly visualized by plotting the three-dimensional distribution of the deviatoric unit-cell volume strain in relation to the cylindrical axis of the DAC and indicates that, if the elasticity of a perovskite is nearly isotropic as it is for CaTiO3, the other two factors become relatively insignificant. PMID- 22037223 TI - Ultrasound-guided cannulation of the great saphenous vein at the ankle in infants. AB - BACKGROUND: The establishment of peripheral venous access in infants is the most common invasive technique in paediatric anaesthesia. Venous puncture can be challenging due to the small size of vessels in this patient population. The present study was designed to investigate the practicability of ultrasound-guided vascular access to the great saphenous vein (GSV) at the level of the medial malleolus in infants <= 12 months. METHODS: Ninety consecutive infants <= 12 months undergoing elective surgery were included in this prospective study and divided into two age groups (0-6 and 7-12 months). After anaesthesia induction with sevoflurane, an ultrasound investigation of both GSVs at the level of the medial malleoli was performed. Subsequently, venous access in one GSV was established under direct ultrasound control. Anatomical ultrasound data and success rates of venous accesses were analysed. RESULTS: While not deeper relative to the skin, the GSV was significantly larger in older infants. The success rate in infants <= 6 months was 96%, whereas in older infants, the success rate was 100%. The overall success rate in all infants was 98%. CONCLUSIONS: Ultrasound facilitates venous puncture of the GSV in the vast majority of infants <= 12 months. Direct visualization via ultrasound is a promising technique for the establishment of venous access in the GSV at the level of the medial malleolus in infants. PMID- 22037222 TI - What comes first? The dynamics of cerebral oxygenation and blood flow in response to changes in arterial pressure and intracranial pressure after head injury. AB - BACKGROUND: Brain tissue partial oxygen pressure (Pbt(O(2))) and near-infrared spectroscopy (NIRS) are novel methods to evaluate cerebral oxygenation. We studied the response patterns of Pbt(O(2)), NIRS, and cerebral blood flow velocity (CBFV) to changes in arterial pressure (AP) and intracranial pressure (ICP). METHODS: Digital recordings of multimodal brain monitoring from 42 head injured patients were retrospectively analysed. Response latencies and patterns of Pbt(O(2)), NIRS-derived parameters [tissue oxygenation index (TOI) and total haemoglobin index (THI)], and CBFV reactions to fluctuations of AP and ICP were studied. RESULTS: One hundred and twenty-one events were identified. In reaction to alterations of AP, ICP reacted first [4.3 s; inter-quartile range (IQR) -4.9 to 22.0 s, followed by NIRS-derived parameters and CBFV (10.9 s; IQR: -5.9 to 39.6 s, 12.1 s; IQR: -3.0 to 49.1 s, 14.7 s; IQR: -8.8 to 52.3 s for THI, CBFV, and TOI, respectively), with Pbt(O(2)) reacting last (39.6 s; IQR: 16.4 to 66.0 s). The differences in reaction time between NIRS parameters and Pbt(O(2)) were significant (P<0.001). Similarly when reactions to ICP changes were analysed, NIRS parameters preceded Pbt(O(2)) (7.1 s; IQR: -8.8 to 195.0 s, 18.1 s; IQR: 20.6 to 80.7 s, 22.9 s; IQR: 11.0 to 53.0 s for THI, TOI, and Pbt(O(2)), respectively). Two main patterns of responses to AP changes were identified. With preserved cerebrovascular reactivity, TOI and Pbt(O(2)) followed the direction of AP. With impaired cerebrovascular reactivity, TOI and Pbt(O(2)) decreased while AP and ICP increased. In 77% of events, the direction of TOI changes was concordant with Pbt(O(2)). CONCLUSIONS: NIRS and transcranial Doppler signals reacted first to AP and ICP changes. The reaction of Pbt(O(2)) is delayed. The results imply that the analysed modalities monitor different stages of cerebral oxygenation. PMID- 22037224 TI - Multicentre cohort study of red blood cell use for revision hip arthroplasty and factors associated with greater risk of allogeneic blood transfusion. AB - BACKGROUND: Revision hip arthroplasty (RHA) is associated with high rates of allogeneic blood transfusion (ABT). We aimed to determine factors associated with ABT in patients undergoing RHA in Scottish hospitals, with particular focus on perioperative cell salvage (PCS). METHODS: A prospective observational cohort study of RHA procedures performed in 11 hospitals over 7 months was performed. We recorded predefined patient, surgery-related, and blood conservation factors that may influence perioperative ABT, together with postoperative haemoglobin (Hb) data and ABTs to day 7. We explored factors with strongest independent association with ABT during the perioperative period using multiple regression analysis. RESULTS: Two hundred and ten cases were studied, of whom 58% received ABTs (mean 1.8 units), most of which (52%) occurred on the day of surgery. Eighty eight (42%) patients received PCS, of whom 68 had red cells re-infused [mean re infusion volume 312 ml (1st, 3rd quartile: 260, 363 ml)]. In unadjusted comparisons, patients receiving PCS had lower intraoperative (9% vs 40%) and total (55% vs 63%) exposure to ABTs. The mean (95% confidence interval) theatre blood loss was 1013 (899-1128) ml and was higher for combined femoral/acetabular revision and femoral revision than other categories. The mean postoperative Hb transfusion trigger was 80 g litre(-1). In multivariable models, preoperative Hb [odds ratio (OR) 0.35; P<0.001], patient weight (OR 0.96; P=0.004), operating theatre blood loss (OR 1.002; P<0.001), and re-infusion of PCS blood (OR 0.31; P=0.02) were independent predictors of ABT exposure. CONCLUSIONS: PCS is an effective blood conservation strategy for RHA, especially for patients with preoperative anaemia, low body weight, or both. PMID- 22037225 TI - Simulating face-to-face tracheal intubation of a trapped patient: a randomized comparison of the LMA Fastrach™, the GlideScope™, and the Airtraq™ laryngoscope. AB - BACKGROUND: We undertook a prospective randomized comparison of the LMA FastrachTM, AirtraqTM laryngoscope, and GlideScopeTM used for face-to-face tracheal intubation simulated to mimic an entrapped patient. METHODS: Thirty senior emergency medicine physicians were trained in the use of the LMA FastrachTM, GlideScopeTM, and AirtraqTM laryngoscope with a standard airway trainer manikin (control). Participants were then asked to perform tracheal intubation in two difficult situations simulated on a difficult airway management manikin wearing a cervical collar. In Situation 1, the manikin was in the supine position with a difficult airway caused by stiffening the cervical spine. In Situation 2, the manikin was positioned to simulate face-to-face tracheal intubation. We measured intubation times, success rates for tracheal intubation, and the difficulty of tracheal intubation. Values are means (sd). RESULTS: In control and Situation 1, tracheal intubation details were similar. In Situation 2, face-to-face tracheal intubation success rate was increased with the AirtraqTM (100%), when compared with that of the GlideScopeTM (70%, P<0.05) and LMA FastrachTM (83%, P<0.05). Face-to-face tracheal intubation was less difficult (visual analogue scale: 0-100) with the AirtraqTM 11 (6) when compared with the GlideScopeTM [33 (14) s, P<0.01)] and LMA FastrachTM [22 (21) s, P<0.01]. The face-to-face tracheal intubation time was shorter with the AirtraqTM 14 (6) s than with the GlideScopeTM [27 (18) s, P<0.01] and FastrachTM [28 (10) s, P<0.01]. CONCLUSIONS: The AirtraqTM laryngoscope was superior to both the GlideScopeTM and LMA FastrachTM during simulated face-to-face difficult tracheal intubation. PMID- 22037226 TI - Entecavir plus tenofovir combination as rescue therapy in pre-treated chronic hepatitis B patients: an international multicenter cohort study. AB - BACKGROUND & AIMS: Long-term viral suppression is a major goal to prevent disease progression in patients with HBV. Aim of this study was to investigate the efficacy and safety of entecavir plus tenofovir combination in 57 CHB partial responders or multidrug resistant patients. METHODS: Investigator-initiated open label cohort study. Quantitative HBV-DNA measurement and resistance testing (line probe-assays and direct-sequencing) at baseline and every 3 months. RESULTS: Fifty seven patients (37 HBeAg+), median age 45 years, previously treated with a median of three lines of antiviral therapy (range 1-6), 24/57 with advanced liver disease, were included. Median ALT at baseline was 1.0 ULN (range 0.3-22) and HBV DNA 1.5 * 10(4)IU/ml (range 500-1 * 10(11)IU/ml). Median treatment duration of combination therapy was 21 months. HBV-DNA level dropped 3 logs (median, range 0 8 log; p<0.0001), 51/57 patients became HBV-DNA undetectable, median after 6 months (95% CI, 4.6-7). The probability for HBV DNA suppression was not reduced in patients with adefovir or entecavir resistance or in patients with advanced liver disease. Viral suppression led to decline in ALT (median 0.7 ULN; range 0.2 2.4; p=0.001). Five patients lost HBeAg (after 15, 18, 20, 21, and 27 months, respectively), one patient showed HBs-seroconversion. Patients with advanced disease did not show clinical decompensation, two patients with cirrhosis and undetectable HBV DNA developed HCCs. No death, newly induced renal impairment or lactic acidosis were reported. CONCLUSIONS: Rescue therapy with entecavir and tenofovir in CHB patients harboring viral resistance patterns or showing only partial antiviral responses to preceding therapies was efficient, safe, and well tolerated in patients with and without advanced liver disease (249). PMID- 22037227 TI - p53, a novel regulator of lipid metabolism pathways. AB - BACKGROUND & AIMS: In this study we aimed at characterizing the regulation of hepatic metabolic pathways by the p53 transcription factor. METHODS: Analysis of gene expression following alteration of p53 status in several human- and mouse derived cells using microarray analysis, quantitative real-time PCR, chromatin immunoprecipitation, and reporter gene assays. A functional assay was performed to determine lipid transfer activity. RESULTS: We identified a novel role for the p53 protein in regulating lipid and lipoprotein metabolism, a process not yet conceived as related to p53, which is known mainly for its tumor suppressive functions. We revealed a group of 341 genes whose expression was induced by p53 in the liver-derived cell line HepG2. Twenty of these genes encode proteins involved in many aspects of lipid homeostasis. The mode of regulation of three representative genes (Pltp, Abca12, and Cel) was further characterized. In addition to HepG2, the genes were induced following activation of p53 in human primary hepatic cells isolated from liver donors. p53-dependent regulation of these genes was evident in other cell types namely Hep3B cells, mouse hepatocytes, and fibroblasts. Furthermore, p53 was found to bind to the genes' promoters in designated p53 responsive elements and thereby increase transcription. Importantly, p53 augmented the activity of secreted PLTP, which plays a major role in lipoprotein biology and atherosclerosis pathology. CONCLUSIONS: These findings expose another facet of p53 functions unrelated to tumor suppression and render it a novel regulator of hepatic lipid metabolism and consequently of systemic lipid homeostasis and atherosclerosis development. PMID- 22037228 TI - Effects of clonidine on bilateral pain behaviors and inflammatory response in rats under the state of neuropathic pain. AB - This study was conducted to investigate the effects of clonidine on bilateral pain behaviors and inflammatory responses in neuropathic pain induced by partial sciatic nerve ligation (PSNL), and to better understand whether the antinociception of clonidine was related to alpha(2)-adrenoceptor mechanisms. Rats were divided randomly into five groups: sham-operation with saline, i.p.; PSNL with clonidine (0.2mg/kg) or saline, i.p.; PSNL with yohimbine (2mg/kg) followed by clonidine (0.2mg/kg), i.p.; and PSNL with naloxone (0.3mg/kg) followed by clonidine (0.2mg/kg), i.p. On post-operative days 1, 3, 7, 14, and 21, both ipsilateral and contralateral pain behaviors were measured. In rats receiving antagonists, bilateral behavioral changes were measured on day 14. Bilateral paw pressure threshold and paw withdrawal latencies were measured, and the extent of glial activation was dertermined by measuring macrophage antigen complex-1 (Mac-1) and glial fibrillary acidic protein (GFAP). Additionally, the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6 were determined. PSNL induced bilateral behavioral hyperalgesia, with the ipsilateral level displaying a higher extent of behavior changes than the contralateral side. In addition, the glial activation markers and cytokine production were augmented bilaterally. Clonidine caused significant attenuation of bilateral mechanical allodynia and thermal hyperalgesia, accompanied by inhibition of glial activation and the expression of cytokines. The effects of clonidine were blocked by the alpha(2)-adrenoceptor antagonist yohimbine and partially reversed by the MU opioid receptor antagonist naloxone. These data suggest that the bilateral antinoceptive effects of clonidine might mediate through immunomodulation by acting on alpha(2)-adrenoceptor in rats undergoing neuropathic pain. PMID- 22037229 TI - Permanent expression of midbrain dopaminergic neurons traits in differentiated amniotic epithelial cells. AB - Amniotic epithelial cells (AECs) have been the subject of interest due to their stem cells characteristics. Pluripotency, lack of teratoma formation, low immunogenicity and no ethical issues make them an alternative source of stem cells for generation of dopaminergic neurons in vitro. AECs may differentiate into midbrain dopaminergic neurons in the presence of induction factors which trigger pathway naturally occurring in the mesencephalon during embryogenesis. In this study, we examined whether FGF8 and Sonic hedgehog (Shh) can induce AECs to express permanently midbrain dopaminergic neurons traits. We found that fresh isolated AECs temporarily expressed some neural markers which decreased 7 days after culture. Co-treatment of cells with FGF8 and Shh had synergistic effect on expression of TH, DAT, Pax2, Lmx1b and En1. Shh ceased differentiation in dopaminergic state and decreased DbetaH. HPLC analysis revealed that dopamine was released into the medium upon depolarization, indicating that functional dopaminergic neurons were present in the culture. These results demonstrate that AECs have capability to differentiate into dopaminergic neurons and can be a candidate for cell replacement therapy of Parkinson's disease. PMID- 22037230 TI - Proteomics in asthma and COPD phenotypes and endotypes for biomarker discovery and improved understanding of disease entities. AB - The application of proteomics to respiratory diseases, such as asthma and COPD, has been limited compared to other fields, like cancer. Both asthma and COPD are recognised to be multi-factorial and complex diseases, both consisting of clusters of multiple disease phenotypes. The complexity of these diseases combined with the inaccessibility and invasiveness of disease relevant samples have provided a hurdle to the progress of respiratory proteomics. Advances in proteomic instrumentation and methodology have led to the possibility to identify proteomes in much smaller quantities of biological material. This review focuses on the efforts in respiratory proteomics in relation to asthma and COPD, and the importance of identifying subgroups of disease entities to establish appropriate biomarkers, and to enhance the understanding of underlying mechanisms in each subgroup. Careful phenotype characterisation of patient subpopulations is required to make improvement in the field of heterogeneous diseases such as asthma and COPD, and the clusters of phenotypes are likely to encompass subgroups of disease with distinct molecular mechanisms; endotypes. The utilisation of modern advanced proteomics in endotypes of asthma and COPD will likely contribute to the increased understanding of disease mechanisms, establishment of biomarkers for these endotypes and improved patient care. PMID- 22037231 TI - Harry Belafonte and the secret proteome of coconut milk. AB - The proteome of coconut milk has been extensively mapped via capture at three pH values with combinatorial peptide ligand libraries (CPLL). A grand total of 307 unique gene products could be listed, 200 discovered via CPLL capture, 137 detected in the control, untreated material and 30 species in common between the two sets of data. This is by far the most extensive mapping of coconut milk, in which, up to the present, only a dozen proteins were known, those belonging to the high- to very-high abundance class. The database of coconut contains only 106 proteins: of those, only six are listed in our table. The vast majority of the classified proteins, thus, has been identified only by homologies with sequences deposited in the general viridiplantae database. This unique set of data could be the starting point for nutritionists and researchers involved in nutraceutics for enucleating some proteins responsible for some of the unique beneficial health effects attributed to coconut milk. PMID- 22037232 TI - Analysis of proteomic changes in roots of soybean seedlings during recovery after flooding. AB - A proteomic approach was used to identify proteins involved in post-flooding recovery in soybean roots. Two-day-old soybean seedlings were flooded with water for up to 3 days. After the flooding treatment, seedlings were grown until 7 days after sowing and root proteins were then extracted and separated using two dimensional polyacrylamide gel electrophoresis (2-DE). Comparative analysis of 2 D gels of control and 3 day flooding-experienced soybean root samples revealed 70 differentially expressed protein spots, from which 80 proteins were identified. Many of the differentially expressed proteins are involved in protein destination/storage and metabolic processes. Clustering analysis based on the expression profiles of the 70 differentially expressed protein spots revealed that 3 days of flooding causes significant changes in protein expression, even during post-flooding recovery. Three days of flooding resulted in downregulation of ion transport-related proteins and upregulation of proteins involved in cytoskeletal reorganization, cell expansion, and programmed cell death. Furthermore, 7 proteins involved in cell wall modification and S adenosylmethionine synthesis were identified in roots from seedlings recovering from 1 day of flooding. These results suggest that alteration of cell structure through changes in cell wall metabolism and cytoskeletal organization may be involved in post-flooding recovery processes in soybean seedlings. PMID- 22037233 TI - Intracordal injections with allogenic cartilage in a canine paralyzed vocal fold model: long-term results. AB - OBJECTIVE: To determine whether detergent treated allogenic cartilage can be used as a substitute for autologous cartilage in a canine paralyzed vocal fold model. MATERIAL AND METHODS: Twelve canines underwent a right recurrent laryngeal nerve resection with injections of allogenic auricular cartilage (harvested 7 days prior, treated with detergent, and minced), with a hyaluronic acid hydrogel (0.2 mL) into the right thyroarytenoid muscle, and with a pressure syringe under direct laryngoscopy. Two animals were sacrificed and larynges removed at each time point: 1-, 3-, 6-, 12-, 18-, and 24-months post injection. Hematoxylin-eosin and immunohistochemistry for expression of major histocompatibility complex-II (MHC-II) antigen was measured to assess histomorphology and gross volume and loss of antigenicity of the injected allogenic cartilage. RESULTS: Injected allogenic cartilage maintained its position and volume in the vocalis muscle throughout 24 months. Cartilage was characterized with empty lacunae indicating possible loss of viability. Fibrotic changes were noted in the surrounding cartilage. MCH-II antigen was not identified in the perichondrium and/or cartilage. Inflammatory reaction, granuloma, or foreign body reaction was not observed at any time point. CONCLUSIONS: These preliminary results suggest that allogenic auricular cartilage grafts treated with detergent are well tolerated and may be an effective material for volumetric augmentation in the paralyzed vocal fold. PMID- 22037234 TI - Nitric oxide synthase is not expressed, nor up-regulated in response to cold acclimation in liver or muscle of threespine stickleback (Gasterosteus aculeatus). AB - There are three isoforms of the enzyme nitric oxide synthase (NOS) in mammals: endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS). All three isoforms oxidize arginine to citrulline in a reaction producing nitric oxide (NO), which regulates multiple signaling pathways and physiological functions in mammals. Less is known about NOS in fishes, in which the existence of eNOS is controversial. Nevertheless, multiple adjustments occur during cold acclimation of fishes, several of which are known to be mediated by eNOS and NO in mammals, including mitochondrial biogenesis, vasodilation and angiogenesis. We hypothesized that if NOS was present, and NO stimulated these pathways in fishes, then the activity of NOS would increase during cold acclimation. To test this hypothesis, we measured the activity and mRNA levels of NOS in three tissues (liver, oxidative muscle, glycolytic muscle) known to undergo mitochondrial biogenesis and/or angiogenesis. Measurements were made in the threespine stickleback, Gasterosteus aculeatus acclimated to either warm (20 degrees C) or cold (8 degrees C) temperature for 9weeks. Cold-acclimated fish were harvested on days 1-3, and at weeks 1, 4 and 9 at 8 degrees C, while warm-acclimated fish were harvested on day 0 and after 9 weeks at 20 degrees C. Transcript levels of NOS were quantified using quantitative real-time PCR, and NOS activity was measured using a radiochemical assay, which detected the rate of catabolism of (14)C labeled arginine. Neither NOS activity nor transcripts were detected in oxidative muscle or glycolytic muscle of warm- or cold-acclimated stickleback, although transcript levels of nNOS and NOS activity were detected in brain. Arginine catabolism was detected in liver of animals held at 10 degrees C and 20 degrees C for 9weeks, but was due to arginase activity, rather than NOS. Consistent with this, NOS transcripts were undetectable in liver. The absence of NOS in liver and muscles of stickleback indicates that signaling molecules other than NO likely mediate physiological changes during cold acclimation in stickleback. PMID- 22037236 TI - Fragrance material review on 2-benzylheptanol. AB - A toxicologic and dermatologic review of 2-benzylheptanol when used as a fragrance ingredient is presented. 2-Benzylheptanol is a member of the fragrance structural group Aryl Alkyl Alcohols and is a primary alcohol. The AAAs are a structurally diverse class of fragrance ingredients that includes primary, secondary, and tertiary alkyl alcohols covalently bonded to an aryl (Ar) group, which may be either a substituted or unsubstituted benzene ring. The common structural element for the AAA fragrance ingredients is an alcohol group -C (R1)(R2)OH and generically the AAA fragrances can be represented as an Ar-C (R1)(R2)OH or Ar-Alkyl-C-(R1)(R2)OH group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to this individual fragrance ingredient and is not intended as a stand-alone document. A safety assessment of the entire Aryl Alkyl Alcohols will be published simultaneously with this document; please refer to Belsito et al., 2012 for an overall assessment of the safe use of this material and all other branched chain saturated alcohols in fragrances. PMID- 22037235 TI - Negative regulation of Yap during neuronal differentiation. AB - Regulated proliferation and cell cycle exit are essential aspects of neurogenesis. The Yap transcriptional coactivator controls proliferation in a variety of tissues during development, and this activity is negatively regulated by kinases in the Hippo signaling pathway. We find that Yap is expressed in mitotic mouse retinal progenitors and it is downregulated during neuronal differentiation. Forced expression of Yap prolongs proliferation in the postnatal mouse retina, whereas inhibition of Yap by RNA interference (RNAi) decreases proliferation and increases differentiation. We show Yap is subject to post translational inhibition in the retina, and also downregulated at the level of mRNA expression. Using a cell culture model, we find that expression of the proneural basic helix-loop-helix (bHLH) transcription factors Neurog2 or Ascl1 downregulates Yap mRNA levels, and simultaneously inhibits Yap protein via activation of the Lats1 and/or Lats2 kinases. Conversely, overexpression of Yap prevents proneural bHLH proteins from initiating cell cycle exit. We propose that mutual inhibition between proneural bHLH proteins and Yap is an important regulator of proliferation and cell cycle exit during mammalian neurogenesis. PMID- 22037237 TI - Comparative evaluation of the hypolipidemic effects of hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) in high fat-fed mice. AB - The effect of hydroxyethyl methylcellulose (HEMC), in comparison with hydroxypropyl methylcellulose (HPMC), on the body weight and lipid metabolism in mice fed with high fat diet was investigated. The animals were given normal control diet (NC group), high fat diet (HF group), or high fat diet supplemented with either HEMC (HF+HEMC group) or HPMC (HF+HPMC group) for 6weeks. At the end of the experimental period, both HF+HEMC and HF+HPMC groups showed reduced body weight, body fat, plasma triglyceride and total cholesterol contents, atherogenic index and free fatty acid level, and increased HDL-cholesterol concentration relative to the HF group. The hypolipidemic effect was partly due to the inhibition of lipogenesis and regulation of adipokine production. These findings demonstrate that compared with HPMC, HEMC was similarly effective in improving the lipid metabolism under high fat diet condition and may be useful in the prevention and treatment of high fat diet-induced hyperlipidemia. PMID- 22037238 TI - Harmaline and harmalol inhibit the carcinogen-activating enzyme CYP1A1 via transcriptional and posttranslational mechanisms. AB - Dioxins are known to cause several human cancers through activation of the aryl hydrocarbon receptor (AhR). Harmaline and harmalol are dihydro-beta-carboline compounds present in several medicinal plants such as Peganum harmala. We have previously demonstrated the ability of P. harmala extract to inhibit TCDD mediated induction of Cyp1a1 in murine hepatoma Hepa 1c1c7 cells. Therefore, the aim of this study is to examine the effect of harmaline and its main metabolite, harmalol, on dioxin-mediated induction of CYP1A1 in human hepatoma HepG2 cells. Our results showed that harmaline and harmalol at concentrations of (0.5-12.5MUM) significantly inhibited the dioxin-induced CYP1A1 at mRNA, protein and activity levels in a concentration-dependent manner. The role of AhR was determined by the inhibition of the TCDD-mediated induction of AhR-dependent luciferase activity and the AhR/ARNT/XRE formation by both harmaline and harmalol. In addition, harmaline significantly displaced [(3)H]TCDD in the competitive ligand binding assay. At posttranslational level, both harmaline and harmalol decreased the protein stability of CYP1A1, suggesting that posttranslational modifications are involved. Moreover, the posttranslational modifications of harmaline and harmalol involve ubiquitin-proteasomal pathway and direct inhibitory effects of both compounds on CYP1A1 enzyme. These data suggest that harmaline and harmalol are promising agents for preventing dioxin-mediated effects. PMID- 22037239 TI - Antidepressant prescribing patterns in the nursing home: second-generation issues revisited. AB - INTRODUCTION: The object of this study was to provide an updated evaluation of the quality of antidepressant management and prescribing patterns in nursing homes in the context of organizational and resident factors. DESIGN: Pearson correlation and chi-square analyses were conducted using information gathered from random nursing home charts. SETTING: Nursing home facilities in and around the Louisville, KY, metropolitan area (n = 10). PARTICIPANTS: Chart reviews were randomly chosen for 20% of long term care resident records in participating homes (n = 209). MEASUREMENTS: Demographic information, documentation of depression diagnoses, and antidepressant prescribing patterns were evaluated using the Quality of Depression Management and Antidepressant Prescribing rating scale and information found in the Minimum Data Set 2.0. RESULTS: Of the sample, 59.8% was prescribed antidepressants at the time of the chart review; 205 chart reviews indicated the absence or presence of a depression diagnosis. For those with documented depression diagnoses (n = 126), nearly one-quarter were not prescribed antidepressants. Of 79 chart reviews indicating no depression diagnosis, nearly a third were receiving an antidepressant. Documentation related to changes in dosing, the presence or absence of side effects, or reasons for continuation were suboptimal. CONCLUSION: Discrepancy between antidepressant prescribing and the presence/absence of depression diagnoses continue to exist for nursing home residents. The quality of antidepressant documentation in nursing home charts continues to be inadequate. Future research should aim to explore possible solutions to these discrepancies and deficiencies in documentation. PMID- 22037240 TI - Do SSRIs play a role in decreasing bone mineral density? AB - Osteoporosis is expected to increase as our population pyramid shifts toward old age. It is associated with increased risk of fractures, leading to complications of limitation of ambulation, loss of independence, and chronic pain. Depression is also a common occurrence in the elderly population. Currently, up to 35% of residents in long term care may experience either major depression or clinically significant depressive symptoms. Selective serotonin receptor inhibitors constitute 62% of all antidepressant drug prescribing. Recently, serotonin transporters have been described in bone, raising the question of whether medications that block serotonin reuptake could affect bone metabolism and ultimately affect osteoporosis-related fractures. Current evidence suggests that depression, particularly in the setting of selective serotonin receptor inhibitors use, should be considered as an addition to the list of risk factors prompting clinicians to evaluate bone health status. PMID- 22037241 TI - Nursing's central role in the care of individuals with cancer: 1900-1940. AB - PURPOSE/OBJECTIVES: To document the central role of nursing care in the continuum of cancer awareness, treatment, and palliation from 1900-1940. DATA SOURCES: Primary sources were student nurses' lecture notes, hospitals' annual reports and other literature, and published materials of the period. DATA SYNTHESIS: Throughout the years reviewed, the warning signs of many types of cancer were included in nurses' education. Nurses were integral to the care and well-being of individuals diagnosed with cancer. CONCLUSIONS: In the first four decades of the 20th century, nursing care of individuals with cancer became increasingly technical and specialized. This article documents the nursing care that was practiced at the time. The issue of concealment of a cancer diagnosis affected nurses' care. Nurses were seen by the American Society for the Control of Cancer as key players in the public's awareness of cancer. IMPLICATIONS FOR NURSING: The care, skill, and knowledge of nurses were central to patients coping with a cancer diagnosis. PMID- 22037242 TI - Driving forces that transformed the care of individuals with cancer from 1900 1940. AB - PURPOSE/OBJECTIVES: To identify driving forces that established the groundwork for a more dedicated approach to health care for individuals with cancer in the early 20th century. DATA SOURCES: Letters, books, and journal articles published in the early 20th century, as well as materials and communications from several archival sources. DATA SYNTHESIS: The increasing incidence of cancer cases and the building of cancer hospitals were among the dramatic forces in the late 19th century that contributed to the transformation of the clinical care of individuals with advanced cancer. Historical research provided evidence for the early development of the specialization of oncology nursing. CONCLUSIONS: In the late 19th and early 20th centuries, the stigma attached to cancer contributed to delays in diagnosis. The great majority of patients were diagnosed with advanced diseases that were incurable. Providing care to patients with cancer was a problem in hospitals and homes. Radical surgeries and the therapeutic use of radium placed unique demands on patients, their family caregivers, and nurses. Nurses adopted new roles and provided detailed bedside care routines; educated patients, families, and the public; published journal articles and textbooks; and advocated for change. IMPLICATIONS FOR NURSING: Early leaders provided the vision, established the foundation, and cultivated the passion for the emergence of specialized nurses to provide individualized care to patients with cancer. Oncology nurses and nurse leaders are needed to sustain the continual transformation of the specialty so that the individualized needs of patients with cancer are met. PMID- 22037243 TI - Cancer nursing: the modern era. AB - PURPOSE/OBJECTIVES: To identify critical elements of the major shift in cancer nursing practice, education, and the expectations of professional nursing immediately following World War II that were precursors of contemporary oncology nursing preparation and practice. DATA SOURCES: General healthcare, medical, and nursing literature, particularly in the American Journal of Nursing, published after World War II and before the inception of the Oncology Nursing Society (ONS); archival materials in the collection of ONS; nursing history literature; and personal communications. DATA SYNTHESIS: Nurses in a wide variety of practice settings with varied levels of experience, including staff nurses, homecare nurses, and high-level leaders and decision makers of the time, were responsible for bringing attention to and addressing the challenges and joys of cancer nursing. CONCLUSIONS: Professional nursing in general and cancer nursing in particular underwent significant changes and a distinct paradigm shift in cancer nursing education and practice in the period of time surrounding World War II, which promoted the advancement of cancer nursing. IMPLICATIONS FOR NURSING: This historical review provides lessons for contemporary cancer nursing clinicians, executives, researchers, and educators with regard to imagining ways to approach issues, the necessity of collaboration and public-private partnerships, and maintaining the passion for this increasingly complex nursing specialty. PMID- 22037244 TI - Adjuvant radiotherapy on older and oldest breast cancer patients after conservative surgery: a retrospective analysis. AB - Purpose of this study was to evaluate the impact of adjuvant radiotherapy, in terms of feasibility and activity, in women aged >= 75 years with early (stage) breast cancer. From January 2000 to December 2007, 131 consecutive patients aged 75 years or older received adjuvant radiotherapy after breast conserving surgery. Eighty-two patients received radiotherapy in combination with 5 years of hormone therapy with tamoxifen or aromatase inhibitor. Thirty out of 131 received chemotherapy. Variables considered were age, stage, co-morbidity, performance status, radiation dose (boost), hormone therapy and chemotherapy. The mean age was 78.3 years (range 75-88 years). A total of 19.1% of the patients had no co morbidity, 57.38% mild, 19.8% moderate, and 3.8% had severe co-morbidities. All patients but one completed the planned radiation schedule. At a median follow-up of 56 months, the 5-year overall survival rate was 78.8%. There was a better survival for patients with no or mild co-morbidities (p<0.0001). The disease-free survival at 5 years was 89.6%. No difference in acute and late toxicity rates was found between patients with different ACE-27 (Adult Comorbidity Evaluation-27) indexes and for different age. We conclude that compliance with adjuvant radiotherapy is good and rate of toxicity is acceptable in elderly patients. Patients with no or mild co-morbidities have a significantly better survival. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. Further prospective trials are needed to confirm these results. PMID- 22037245 TI - Drug-using behaviors of the elderly living in nursing homes and community dwellings in Manisa, Turkey. AB - AIM: The study aimed to investigate drug-taking behaviors of the elderly living in a nursing home or community dwelling and to determine the factors affecting their behaviors. MATERIALS AND METHODS: This cross-sectional study was conducted on the elderly living at homes (n=106) or in nursing homes (n=220) in the city center of Manisa located in the Aegean region of Turkey. The study data were collected between February 2011 and May 2011. For data collection, three survey forms were used: the socio-demographic questionnaire, the standardized mini mental test and the questionnaire which enquires drug-using behavior. The data were evaluated with SPSS for 15.00 Windows statistical package program. Data descriptive statistics were evaluated with the chi-square test, Student's t-test and logistic regression analysis. RESULTS: The mean age of the whole group was 73.4+/-6.3 (65-94). In the study group, the mean numbers of chronic diseases and medications used were 1.2+/-0.9 (0-5) and 2.6+/-1.8 (0-10), respectively. According to the survey results, those living in nursing homes, males and those with education higher than primary school education displayed better drug-taking behaviors than those living at home, females and those with less than primary school education, respectively. CONCLUSION: The appropriate use of medicine is a major problem in old age. Living at home or in a nursing home, gender and education are important factors affecting the correct use of medicine in old age. PMID- 22037246 TI - Effects of resveratrol on HepG2 cells as revealed by (1)H-NMR based metabolic profiling. AB - BACKGROUND: Resveratrol, a polyphenol found in plant products, has been shown to regulate many cellular processes and to display multiple protective and therapeutic effects. Several in vitro and in vivo studies have demonstrated the influence of resveratrol on multiple intracellular targets that may regulate metabolic homeostasis. METHODS: We analysed the metabolic modifications induced by resveratrol treatment in a human hepatoblastoma line, HepG2 cells, using a (1)H-NMR spectroscopy-based metabolomics approach that allows the simultaneous screening of multiple metabolic pathways. RESULTS: Results demonstrated that cells cultured in the presence or absence of resveratrol displayed different metabolic profiles: the treatment induced a decreased utilisation of glucose and amino acids for purposes of energy production and synthesis associated to a decreased release of lactate in the culture medium and an increase in succinate utilisation. At the same time, resveratrol treatment slowed the cell cycle in the S phase without inducing apoptosis, and increased Sirt1 expression, also affecting its intracellular localisation. CONCLUSIONS: Our results show that the metabolomic analysis of the exometabolome of resveratrol-treated HepG2 cells indicates a metabolic switch from glucose and amino acid utilisation to fat utilisation for the production of energy, and seem in agreement with an effect mediated via AMPK- and Sirt1-activation. GENERAL SIGNIFICANCE: NMR-based metabolomics has been applied in a hepatocyte cell culture model in relation to resveratrol treatment; such an approach could be transferred to evaluate the effects of nutritional compounds with health impact. PMID- 22037247 TI - In vivo measurement of muscle output in intact Drosophila. AB - We describe our methods for analysing muscle function in a whole intact small insect, taking advantage of a simple flexible optical beam to produce an inexpensive transducer with wide application. We review our previous data measuring the response to a single action potential driven muscle twitch to explore jumping behaviour in Drosophila melanogaster. In the fruitfly, where the sophisticated and powerful genetic toolbox is being widely employed to investigate neuromuscular function, we further demonstrate the use of the apparatus to analyse in detail, within whole flies, neuronal and muscle mutations affecting activation of muscle contraction in the jump muscle. We have now extended the use of the apparatus to record the muscle forces during larval and other aspects of adult locomotion. The robustness, simplicity and versatility of the apparatus are key to these measurements. PMID- 22037248 TI - Determination of deoxynivalenol in cereals by immunoaffinity clean-up and ultra high performance liquid chromatography tandem mass spectrometry. AB - An immunoaffinity column (IAC) was prepared with a new deoxynivalenol (DON) monoclonal antibody and used as a clean-up tool before ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis of DON in cereals. The developed IAC clean-up method showed high recoveries for DON. They ranged from 61% to 103% in wheat, rice, and millet with intra-day and inter-day variations below 19% and 17%, respectively. The column capacity was 2.86MUg DON per mL of gel, and it maintained above 0.68MUg/mL of gel after 10 cycles of usage at 2 days intervals. The limit of detection (LOD) and limit of quantification (LOQ) were 0.3 and 0.8MUg/kg, respectively. Twenty-one out of 40 analyzed commercial cereal samples were positive at DON concentrations from 7 to 534MUg/kg. PMID- 22037249 TI - Functional inhibition of transitory proteins by intrabody-mediated retention in the endoplasmatic reticulum. AB - Intrabodies are recombinantly expressed intracellular antibody fragments that can be used to specifically bind and inhibit the function of cellular proteins of interest. Intrabodies can be targeted to various cell compartments by attaching an appropriate localization peptide sequence to them. An efficient strategy with a high success rate is to anchor intrabodies in the endoplasmatic reticulum where they can inhibit transitory target proteins by binding and preventing them to reach their site of action. Intrabodies can be assembled from antibody gene fragments from various sources into dedicated expression vectors. Conventionally, antibody cDNA sequences are derived from selected hybridoma cell clones that express antibodies with the desired specificity. Alternatively, appropriate clones can be isolated by affinity selection from an antibody in vitro display library. Here an evaluation of endoplasmatic reticulum targeted intrabodies with respect to other knockdown approaches is given and the characteristics of various intrabody expression vectors are discussed. A step by step protocol is provided that was repeatedly used to construct intrabodies derived from diverse antibody isotypes producing hybridoma cell clones. The inactivation of the cell surface receptor neural cell adhesion molecule (NCAM) by a highly efficacious novel endoplasmatic reticulum-anchored intrabody is demonstrated. PMID- 22037250 TI - Oxidative metabolism of dehydroepiandrosterone (DHEA) and biologically active oxygenated metabolites of DHEA and epiandrosterone (EpiA)--recent reports. AB - Dehydroepiandrosterone (DHEA) is a multifunctional steroid with a broad range of biological effects in humans and animals. DHEA can be converted to multiple oxygenated metabolites in the brain and peripheral tissues. The mechanisms by which DHEA exerts its effects are not well understood. However, evidence that the effects of DHEA are mediated by its oxygenated metabolites has accumulated. This paper will review the panel of oxygenated DHEA metabolites (7, 16 and 17 hydroxylated derivatives) including a number of 5alpha-androstane derivatives, such as epiandrosterone (EpiA) metabolites. The most important aspects of the oxidative metabolism of DHEA in the liver, intestine and brain are described. Then, this article reviews the reported biological effects of oxygenated DHEA metabolites from recent findings with a specific focus on cancer, inflammatory and immune processes, osteoporosis, thermogenesis, adipogenesis, the cardiovascular system, the brain and the estrogen and androgen receptors. PMID- 22037251 TI - Host-derived MCP-1 and MIP-1alpha regulate protective anti-tumor immunity to localized and metastatic B16 melanoma. AB - Leukocytic infiltration into malignant melanoma lesions is tightly regulated by chemokines. To assess the role of the CC chemokines monocyte chemotactic protein 1 (MCP-1/chemokine ligand 2) and macrophage inflammatory protein-1alpha (MIP 1alpha/chemokine ligand 3) in this process, s.c. primary and metastatic B16 F10 melanoma tumor growth levels were examined in mice lacking MCP-1 or MIP-1alpha. Primary s.c. B16 F10 melanoma growth was augmented by loss of MCP-1 or MIP 1alpha. Similarly, lung metastasis was enhanced by the deficiency of MCP-1 or MIP 1alpha. Enhanced tumor outgrowth was associated with decreased percentages of infiltrating CD4(+) T cells, CD8(+) T cells, and natural killer cells. In the absence of MCP-1 or MIP-1alpha, melanoma outgrowth was correlated with reduced local expression of interferon-gamma, IL-6, tumor necrosis factor-alpha, and transforming growth factor-beta. Among these cytokines, reduced expression levels of interferon-gamma and tumor necrosis factor-alpha on leukocytes from the spleen were associated with the development of lung metastasis in chemokine-deficient mice. The local s.c. administration of these four cytokines significantly augmented another chemokine's expression and suppressed primary melanoma growth in mice deficient for MCP-1 or MIP-1alpha. The s.c. injection of MCP-1 or MIP 1alpha significantly inhibited the primary tumor growth in wild-type mice. These results indicate that host-derived MCP-1 and MIP-1alpha regulate protective anti tumor immunity to B16 F10 melanoma by promoting lymphocyte infiltration into the tumor and subsequent cytokine production. PMID- 22037252 TI - Design, synthesis and antiepileptic properties of novel 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl)urea derivatives. AB - Twenty new 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3 dioxoindolin-5-yl) urea derivatives were designed and synthesized. Antiepileptic screening was performed using MES and scPTZ seizures tests. The neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 5c, 5g, 5j and 5n were found active in MES model, while 5o showed significant antiepileptic activity in scPTZ model. Further all these five compounds were administered orally to rats, 5c, 5g and 5n showed better activity than Phenytoin in oral route. Among these compounds 5c revealed protection in MES at a dose of 30 mg/kg and 100 mg/kg 0.5 h and 4 h after i.p. administration respectively. This molecule provided also protection in the scPTZ at a dose of 300 mg/kg in both time intervals. PMID- 22037253 TI - Triazole ring-opening leads to the discovery of potent nonsteroidal 17beta hydroxysteroid dehydrogenase type 2 inhibitors. AB - 17beta-Hydroxysteroid dehydrogenase type 2 (17beta-HSD2) catalyzes the oxidation of the highly potent steroids: the estrogen estradiol (E2) and the androgen testosterone (T) to the less active estrone and androstenedione, respectively. Inhibition of this enzyme may help maintain the local E2 level in bone tissue when the circulating E2 level drops and is therefore a novel and promising approach for the treatment of osteoporosis. In this work, a series of new nonsteroidal and achiral 17beta-HSD2 inhibitors, namely N-benzyl-diphenyl-3(or 4) carboxamide and N-benzyl-5-phenyl-thiophene-2-carboxamide was designed and the compounds were synthesized in a two to three steps reaction. A small library was built applying parallel synthesis. Highly potent 17beta-HSD2 inhibitors could be identified in the thiophene-2-carboxamide class with IC(50) in the low nanomolar range. These compounds also showed a good selectivity profile toward 17beta-HSD1 and toward the estrogen receptors alpha and beta. The most interesting 17beta HSD2 inhibitor identified in this study is the 5-(2-fluoro-3-methoxyphenyl)-N-(3 hydroxybenzyl)-N-methylthiophene-2-carboxamide 6w displaying an IC(50) of 61 nM and a selectivity factor of 73 toward 17beta-HSD1. PMID- 22037254 TI - Morgana and melusin: two fairies chaperoning signal transduction. AB - Chaperones and scaffold proteins are key elements involved in controlling the assembly of molecular complexes required for coordinated signal transduction. Here we describe morgana and melusin, two phylogenetically conserved chaperones that cooperate with Hsp90 and regulate signal transduction in important physiopathological processes. While morgana is ubiquitously expressed, melusin expression is restricted to striated muscles. Despite high sequence homology, the two chaperones have distinct functions. Morgana controls genomic stability by regulating the centrosome cycle via ROCKII kinase. Melusin, however, organizes ERK signal transduction in cardiomyocytes and regulates cardiac compensatory hypertrophy in response to different stress stimuli. PMID- 22037255 TI - Prevalence, frequency, and initiation of hookah tobacco smoking among first-year female college students: a one-year longitudinal study. AB - Hookah tobacco smoking has become increasingly prevalent among college students, but little is known about frequency of use or patterns of use over time, including during the transition to college. The goals of this longitudinal cohort study were to assess the: (a) lifetime prevalence, (b) current prevalence, (c) frequency of use, and (d) pattern of initiation of hookah tobacco smoking among female students during the first year of college. First-year female college students (N=483) at a large private university in upstate New York completed 13 monthly online surveys about their hookah tobacco use from August 2009 to August 2010. Lifetime prevalence of hookah use increased from 29% at college entry to 45% at one-year follow-up. The highest rates of hookah initiation occurred in the first two months of students' first semester of college. Current (past 30 days) hookah use ranged from 5% to 13% during the year after college entry. On average, hookah users reported smoking hookah two days per month. Hookah tobacco use is common among female college students. The transition to college is a vulnerable time for hookah initiation. Preventive efforts should begin in high school and continue through college, with a focus on students' first few months on campus. PMID- 22037256 TI - N-terminal PAX8 polyclonal antibody shows cross-reactivity with N-terminal region of PAX5 and is responsible for reports of PAX8 positivity in malignant lymphomas. AB - Recently, reports using immunohistochemistry and a polyclonal antibody directed against the N-terminal region of PAX8 describe PAX8 expression in malignant lymphomas. As the N-terminal regions of PAX family members, including the B-cell transcription factor PAX5, have high sequence homology, we investigated PAX8 positivity in malignant lymphomas. Comparative sequence analysis between the N- and C-terminal regions of PAX8 and PAX5 proteins confirmed homologies of 70% and 39%, respectively. We then compared the results using N-terminal (high homology) and C-terminal (lower homology) anti-PAX8 antibodies to assess PAX8 expression in reactive tissues, diffuse large B-cell lymphoma and classical Hodgkin lymphoma, using routine immunohistochemical methods. Expression of PAX8 was also assessed in diffuse large B-cell lymphoma and classical Hodgkin lymphoma cell lines using real-time qRT-PCR methods. Our results show that reactive and neoplastic B-cells are positive for PAX8 using the N-terminal antibody, but negative for PAX8 when the C-terminal antibody was used. PAX8 mRNA levels were not detected in any of the B-cell lymphoma cell lines studied. These results indicate that benign and malignant B-cells do not express PAX8. We conclude that positivity for PAX8 reported by others in B-cell lymphomas is likely due to cross-reactivity between the N-terminal regions of PAX8 and PAX5, due to the high sequence homology of these two regions. PMID- 22037257 TI - Distinct patterns of promoter CpG island methylation of breast cancer subtypes are associated with stem cell phenotypes. AB - Although DNA methylation profiles in breast cancer have been connected to breast cancer molecular subtype, there have been no studies of the association of DNA methylation with stem cell phenotype. This study was designed to evaluate the promoter CpG island methylation of 15 genes in relation to breast cancer subtype, and to investigate whether the patterns of CpG island methylation in each subtype are associated with their cancer stem cell phenotype represented by CD44+/CD24- and ALDH1 expression. We performed MethyLight analysis of the methylation status of 15 promoter CpG island loci involved in breast cancer progression (APC, DLEC1, GRIN2B, GSTP1, HOXA1, HOXA10, IGF2, MT1G, RARB, RASSF1A, RUNX3, SCGB3A1, SFRP1, SFRP4, and TMEFF2) and determined cancer stem cell phenotype by CD44/CD24 and ALDH1 immunohistochemistry in 36 luminal A, 33 luminal B, 30 luminal-HER2, 40 HER2 enriched, and 40 basal-like subtypes of breast cancer. The number of CpG island loci methylated differed significantly between subtypes, and was highest in the luminal-HER2 subtype and lowest in the basal-like subtype. Methylation frequencies and levels in 12 of the 15 genes differed significantly between subtypes, and the basal-like subtype had significantly lower methylation frequencies and levels in nine of the genes than the other subtypes. CD44+/CD24- and ALDH1+ putative stem cell populations were most enriched in the basal-like subtype. Methylation of promoter CpG islands was significantly lower in CD44+/CD24-cell (+) tumors than in CD44+/CD24-cell (-) tumors, even within the basal-like subtype. ALDH1 (+) tumors were also less methylated than ALDH1 (-) tumors. Our findings showed that promoter CpG island methylation was different in relation to breast cancer subtype and stem cell phenotype of tumor, suggesting that breast cancers have distinct patterns of CpG island methylation according to molecular subtypes and these are associated with different stem cell phenotypes of the tumor. PMID- 22037259 TI - Chemotherapy-related leiomyopathy: a suggested morphological explanation for the intestinal dysmotility affecting patients treated with anthracyclines. AB - Anthracycline, used in oncological chemotherapy, has one well-known side effect: cardiotoxicity. Another is abnormal intestinal motility such as constipation and ileus, the pathogenesis of which, to our knowledge, has not been morphologically investigated. We conducted a study in search of morphological evidence that might shed some light on the pathogenesis of the motility dysfunction. Autopsies performed between 2002 and 2007 were reviewed to select cases of children who had received anthracycline therapy for various neoplasms. The seven patients found had leukemias, lymphomas, or renal solid tumors. They all suffered from constipation or intestinal dysmotility, and no case of anthracyclin-treated neoplasia without the side effect was found in the files. Tissue samples from the heart, gastrointestinal tract, uterus, urinary bladder, and skeletal muscles were examined by light and electron microscopy. As described by others, the myocardium of all anthracycline-treated patients showed loss of myofilaments, fibrosis, mitochondrial proliferation, and pools of accumulated Z-band material. In the gastrointestinal tract and other smooth muscle-endowed organs such as muscular blood vessels, bladder and uterus, the muscularis displayed hyalinization and disorganization, including loss of myofilaments and moderate-severe fibrosis. This study illustrates changes in the smooth muscle, and that of the gastrointestinal tracts and their vessels in particular, in patients treated with anthracycline, who had experienced motility dysfunction associated with their chemotherapy, suggesting that, in addition to the heart, anthracycline may also damage smooth muscle fibers and thus be instrumental in the pathogenesis of the side effects. PMID- 22037258 TI - The distribution of immunomodulatory cells in the lungs of patients with idiopathic pulmonary fibrosis. AB - We have characterized the immune system involvement in the disease processes of idiopathic pulmonary fibrosis in novel ways. To do so, we analyzed lung tissue from 21 cases of idiopathic pulmonary fibrosis and 21 (non-fibrotic, non cancerous) controls for immune cell and inflammation-related markers. The immunohistochemical analysis of the tissue was grouped by patterns of severity in disease pathology. There were significantly greater numbers of CD68(+) and CD80(+) cells and significantly fewer CD3(+), CD4(+), and CD45RO(+) cells in areas of relatively (histologically) normal lung in biopsy samples from idiopathic pulmonary fibrosis patients compared with controls. In zones of active disease, characterized by epithelial cell regeneration and fibrosis, there were significantly more cells expressing CD4, CD8, CD20, CD68, CD80, chemokine receptor 6 (CCR6), S100, IL-17, tumor necrosis factor-alpha, and retinoic acid related orphan receptors compared with histologically normal lung areas from idiopathic pulmonary fibrosis patients. Inflammation was implicated in these active regions by the cells that expressed retinoid orphan receptor-alpha, -beta, and -gamma, CCR6, and IL-17. The regenerating epithelial cells predominantly expressed these pro-inflammatory molecules, as evidenced by co-expression analyses with epithelial cytokeratins. Macrophages in pseudo-alveoli and CD3(+) T cells in the fibrotic interstitium also expressed IL-17. Co-expression of IL-17 with retinoid orphan receptors and epithelial cytoskeletal proteins, CD68, and CD3 in epithelial cells, macrophages, and T-cells, respectively, confirmed the production of IL-17 by these cell types. There was little staining for forkhead box p3, CD56, or CD34 in any idiopathic pulmonary fibrosis lung regions. The fibrotic regions had fewer immune cells overall. In summary, our study shows participation of innate and adaptive mononuclear cells in active-disease regions of idiopathic pulmonary fibrosis lung, where the regenerating epithelial cells appear to propagate inflammation. The regenerative mechanisms become skewed to ultimately result in lethal, fibrotic restriction of lung function. PMID- 22037260 TI - Molecular heterogeneity of TFE3 activation in renal cell carcinomas. AB - Renal cell carcinomas associated with Xp11.2 translocations have recently been identified as a distinct biological entity. The translocation results in the fusion of the transcription factor TFE3 to one of several different fusion partners including PRCC, PSF, NONO, ASPL or CTLC with consecutive overexpression of the chimeric protein. As the true frequency of these neoplasms as well as the biological properties of TFE3 activation in renal cell carcinomas are largely unknown, we have examined TFE3 expression as well as the underlying genetic alterations in a large, hospital-based series of renal cell carcinomas with long term follow-up information. Out of a total of 876 tumours, TFE3 translocations were detected in five cases (0.6%). Three additional cases were identified in a second series of cases comprising of renal cell carcinomas developing in patients before the age of 50. However, using immunohistochemistry, 9% of all renal cell carcinomas showed some degree of TFE3 reactivity. Interestingly, these cases were associated with high nuclear grade, greater tumour extent and metastatic disease as well as an unfavourable patient outcome on uni- and multivariate analysis. Fluorescence in situ hybridisation (FISH) revealed TFE3 amplifications as an additional, novel mechanism leading to increased TFE3 expression levels. In conclusion, our data show that Xp11 translocation renal cell carcinomas are uncommon tumours accounting for <1% of adult renal cell carcinomas and that the diagnosis of Xp11 translocation renal cell carcinomas needs to be verified using molecular techniques. In turn, TFE3 overexpressing tumours show an aggressive behaviour and Xp11 translocation is only one of several possible underlying genomic alterations. PMID- 22037261 TI - Mesotheliomas with crystalloid structures: report of nine cases, including one with oncocytic features. AB - Although the presence of crystalloids has historically been of largely academic interest or simply an intriguing curiosity, these structures have occasionally been useful in the differential diagnosis of some tumors. Crystalloids have only rarely been reported in mesotheliomas, and their presence in these tumors has not been sufficiently investigated, nor has their potential value as an ultrastructural marker for mesothelioma been established. The finding of a case of mesothelioma in which the vast majority of the neoplastic cells contained intracytoplasmic crystalloids prompted a search for these structures in 69 consecutive cases of mesothelioma (59 epithelioid, 7 sarcomatoid, 3 mixed epithelioid sarcomatoid). Crystalloids were found in 9 (15%) of the 59 epithelioid mesotheliomas, indicating that these structures are not as rare as had been thought. That these inclusions were demonstrated in tumors exhibiting diverse histological patterns and were not confined to a single subtype of epithelioid mesothelioma indicates that, because of their unique morphology, when present, they can assist in the diagnosis of these tumors. In addition, oncocytic features were also seen in one of the cases with crystalloid inclusions. Pathologists should be aware of the fact that, even though uncommon, mesotheliomas can present oncocytic morphology and, therefore, these tumors should be included in the differential diagnosis of those neoplasms that display similar morphological features, and which can metastasize to the serosal membranes. To my knowledge, an oncocytic mesothelioma has not previously been reported. PMID- 22037262 TI - C4d/CD34 double-immunofluorescence staining of renal allograft biopsies for assessing peritubular capillary C4d positivity. AB - Immunofluorescence detection of the complement split product C4d along peritubular capillaries in renal allograft biopsies is the mainstay for the diagnosis of antibody-mediated rejection. The extent of peritubular capillary C4d positivity may have significant clinical ramifications; however, peritubular capillary density in the renal cortex is often difficult to assess with single channel immunofluorescence. In this study, we report a C4d/CD34 double immunofluorescence staining protocol for renal allograft frozen sections that allows rapid and sensitive detection of C4d positivity, as well as improved accuracy in estimating the C4d-positive fraction of peritubular capillaries. In addition, this method aids in determining whether C4d-positive structures correspond to peritubular capillaries or whether they represent common mimics of peritubular capillaries such as tubular basement membranes. C4d/CD34 double immunofluorescence provides rapid, convenient, and low-cost implementation for laboratories currently utilizing single-channel C4d immunofluorescence. PMID- 22037263 TI - Histone deacetylase 1 and 2 in mesenchymal tumors. AB - Histone deacetylases (HDACs) have a critical role in epigenetic gene silencing, rendering a compact chromatin structure by removing acetyl groups from lysine residues within the tails of core histones, thereby repressing gene expression. Epigenetic transcriptional dysregulation is an important oncogenic mechanism in some sarcomas associated with translocations, for which antitumor activity by HDAC inhibitors has been shown in preclinical studies. Nevertheless, the expression of the protein targets of these drugs has not yet been broadly surveyed in this neoplasia. In this study, we assess the expression of HDAC1 and 2 by immunohistochemistry in a tissue microarray series of 1332 cases, representing 44 categories of malignant and borderline mesenchymal tumors. HDAC2 was the more highly expressed isoform, and was more strongly expressed in translocation-associated sarcomas than in other mesenchymal tumors or normal tissues. HDAC1, in contrast, displayed lower expression in translocation associated sarcomas than in other mesenchymal tumors or in normal tissues. These results indicate that HDAC1 and HDAC2 are differentially expressed in mesenchymal neoplasms, and suggest that HDAC2 is the isoform more likely contributing to the pathogenesis of many translocation-associated sarcomas and to their response to HDAC inhibitors. PMID- 22037264 TI - Factors that influence primary cilium length. AB - Almost all mammalian cells carry one primary cilium that functions as a biosensor for chemical and mechanical stimuli. Genetic damages that compromise cilia formation or function cause a spectrum of disorders referred to as ciliapathies. Recent studies have demonstrated that some pharmacological agents and extracellular environmental changes can alter primary cilium length. Renal injury is a well-known example of an environmental insult that triggers cilia length modification. Lithium treatment causes primary cilia to extend in several cell types including neuronal cells;this phenomenon is likely independent of glycogen synthase kinase-3beta inhibition. In renal epithelial cell lines, deflection of the primary cilia by fluid shear shortens them by reducing the intracellular cyclic AMP level, leading to a subsequent decrease in mechanosensitivity to fluid shear. Primary cilium length is also influenced by the dynamics of actin filaments and microtubules through the levels of soluble tubulin in the cytosol available for primary cilia extension. Thus, mammalian cells can adapt to the extracellular environment by modulating the primary cilium length, and this feedback system utilizing primary cilia might exist throughout the mammalian body. Further investigation is required concerning the precise molecular mechanisms underlying the control of primary cilium length in response to environmental factors. PMID- 22037265 TI - Radiofrequency ablation of lung cancer at Okayama University Hospital: a review of 10 years of experience. AB - The application of radiofrequency ablation for the treatment of lung cancer by our group at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences began in June 2001, and in the present report, we review our 10-year experience with this treatment modality at Okayama University Hospital. The local efficacy of radiofrequency ablation for the treatment of lung cancer depends on tumor size and the type of electrode used, but not on tumor type. An important factor for the prevention of local failure may be the acquisition of an adequate ablative margin. The combination of embolization and radiation therapy enhances the local efficacy. Local failure may be salvaged by repeating the radiofrequency ablation, particularly in small tumors. Survival rates after radiofrequency ablation are quite promising for patients with clinical stage I non-small cell lung cancer and pulmonary metastasis from colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. The complications caused by radiofrequency ablation can be treated conservatively in the majority of cases. However, attention should be paid to rare but serious complications. This review shows that radiofrequency ablation is a promising treatment for patients with lung cancer. PMID- 22037266 TI - Quantitative analysis of DNA degradation in the dead body. AB - Postmortem degradation of DNA was quantitatively estimated. Brain, liver, kidney and muscle samples were obtained from sacrificed rats left at 20C or 4C. The quantity of DNA was measured by real-time PCR using a primer set for a sequence in the Rsrc 1 gene. When the quantity of amplified DNA using 10ng Human Genomic DNA was defined as 100 RFU, the quantities in the brain, liver, kidney and skeletal muscle (each 2MUg of dry weight) on the day of sacrifice were 253+/-11, 338+/-22, 556+/-14 and 531+/-12 Relative Fluorescence Units (RFU), respectively (mean+/-S.E., n=5). The quantity of amplified DNA decreased to below 10 RFU in 1 3 weeks in the liver, kidney and skeletal muscle at 20C, while that in the brain was more than 10 RFU for six weeks, demonstrating the usefulness of the brain as a sample for DNA analysis of decaying corpses. It was suggested that quantifying the amplified DNA in the brain at 20C and in the liver at 4C as well as the ratio of the quantity of amplified DNA in the liver to the brain at 4C might be useful for diagnosing time of death. This study provides the first quantitative analysis of the postmortem progress of DNA degradation in the corpse. PMID- 22037267 TI - Sex difference of in-hospital mortality in patients with acute myocardial infarction. AB - Factors contributing to the sex difference of in-hospital mortality after acute myocardial infarction (MI) are still unknown. We compared the clinical characteristics on admission and in-hospital outcome of consecutive 1,354 patients with acute MI between the 2 sexes. Age on admission was about 7 years older in women than in men. In-hospital death was significantly more frequent in women. Pulmonary congestion and hypertension were more likely in women with higher serum levels of total cholesterol and LDL cholesterol. A higher prevalence of current smoking and inferior wall involvement and lower serum HDL cholesterol level were observed in man. After adjusting for age, adverse in-hospital mortality for women was observed in both younger and older patients. Multivariate logistic regression analysis demonstrated that age, location of infarction, recanalization and serum C-reactive protein (CRP) concentration were independent predictors for in-hospital mortality for overall patients, while age and recanalization were independent predictors for male gender, and pulmonary congestion and serum CRP concentration were independent predictors for female gender. In-hospital outcome after acute MI was worse in women. A multivariate logistic regression model revealed that the sexually different factors affected in-hospital mortality in females. PMID- 22037268 TI - Single nucleotide polymorphism WRN Leu1074Phe is associated with prostate cancer susceptibility in Chinese subjects. AB - Deficiencies in the human DNA repair gene WRN are the cause of Werner syndrome, a rare autosomal recessive disorder characterized by premature aging and a predisposition to cancer. This study evaluated the association of WRN Leu1074Phe (rs1801195), a common missense single nucleotide polymorphism in WRN, with prostate cancer susceptibility in Chinese subjects. One hundred and forty-seven prostate cancer patients and 111 male cancer-free control subjects from 3 university hospitals in China were included. Blood samples were obtained from each subject, and the single nucleotide polymorphism WRN Leu1074Phe was genotyped by using a Snapshot assay. The results showed that WRN Leu1074Phe was associated with the risk of prostate cancer in Chinese men and that the TG/GG genotype displayed a decreased prevalence of prostate cancer compared with the TT genotype (OR=0.58, 95%CI:0.35-0.97, p=0.039). Through stratified analysis, more significant associations were revealed for the TG/GG genotype in the subgroup with diagnosis age <= 72 yr (OR=0.27, 95%CI:0.12-0.61, p=0.002) and in patients with localized diseases (OR=0.36, 95%CI:0.19-0.70, p=0.003). However, no statistically significant difference was found in the subgroup with age >72 yr or in patients with advanced diseases. We concluded that the genetic variant Leu1074Phe in the DNA repair gene WRN might play a role in the risk of prostate cancer in Chinese subjects. PMID- 22037269 TI - Covert laparoscopic cholecystectomy:a new minimally invasive technique. AB - To further improve our developed transumbilical endoscopic surgery (TUES), we developed a completely covert laparoscopic cholecystectomy (LC). Twelve cases of LC were recruited for this new approach. First, a 10-mm trocar was placed above the umbilicus for inserting the laparoscope. Two 5-mm trocars were then placed near the right and left ends of the superior margin of the suprapubic hair. After the 5-mm 30 degrees laparoscope was shifted to the left suprapubic trocar, the harmonic scalper, electric hook, and grasper were inserted either through the 10 mm umbilical trocar or through the right suprapubic trocar. All gallbladders were successfully removed without intraoperative complications. The mean operating time was 28.5 +/- 5.7 min (range 20-45 min). All patients felt well after surgery and did not need postoperative analgesia. They resumed free oral intake 6h after the procedure. All patients were satisfied with the appearance of the incisions, which were completely hidden in the umbilicus and suprapubic hair. The approach we developed has overcome both external instrument interference around the umbilicus and the loss of triangulation in the operative field. It is relatively simpler than a typical TUES and offers better cosmetic results. PMID- 22037270 TI - Risk factors for infection in patients with remitted rheumatic diseases treated with glucocorticoids. AB - It is well known that infection is one of the major causes of morbidity and mortality in rheumatic disease patients treated with high-dose glucocorticoids, especially in the early phase after achievement of disease remission. The aim of this study was to identify the risk factors for infection, with a focus on the dose of glucocorticoids administered, following the achievement of disease remission in rheumatic diseases patients. We retrospectively analyzed the medical records of rheumatic disease patients who had been treated with glucocorticoids. The primary endpoint was the incidence rate of infection during a period from 1 to 2 months after the commencement of treatment. From April 2006 to March 2010, 19 of 92 patients suffered from infection during the observation period. Age ? 65 yrs, presence of interstitial pneumonia, diagnosis of systemic vasculitis and serum creatinine level ? 2.0 mg/dl were found to be univariate predictors for infection. However, only the presence of interstitial pneumonia was an independent risk factor for infection (HR=4.50, 95%CI=1.65 to 14.44) by the Cox proportional hazard model. Even after achievement of clinical remission, careful observation is needed for patients with interstitial pneumonia, more so than for those receiving high-dose glucocorticoids. PMID- 22037271 TI - Monitoring twenty-six chronic myeloid leukemia patients by BCR-ABL mRNA level in bone marrow:a single hospital experience. AB - Chronic myeloid leukemia (CML) is caused by the BCR-ABL oncogene. The Philadelphia chromosome (Ph) from a reciprocal translocation, t(9;22) (q34;q11) causes a fusion gene, BCR-ABL, that encodes a constitutively active tyrosine kinase. Treatment of CML by imatinib is effective to control the tyrosyl phosphorylation of the protein related to the cell signaling. BCR-ABL mRNA is overexpressed in the minimal residual disease (MRD), known as an early sign of relapse. Between December 2005 and June 2008, we measured BCR-ABL mRNA levels in the bone marrow (BM) from patients by quantitative real-time polymerase chain reaction (RQ-PCR) in Aomori Prefectural Central Hospital. Eighty-six samples from 26 patients were collected. Among the 26 CML patients, 11 patients (42%) were in the pretreatment group. Seven (64%) of the 11 patients achieved complete molecular response (CMR). In the post-treatment group consisting of the remaining 15 patients, 9 (60%) patients achieved CMR. The patients receiving imatinib at a dose over 300 mg per day required 13 (6-77) months [median (range)] to achieve CMR. On the other hand, the patients receiving a dose below 300 mg per day required 29.5 (11-84) months [median (range)]. When BCR-ABL mRNA was detected during the treatment course of patients with CMR, careful observation of BCR-ABL mRNA was useful for tracking the clinical course of patients. In conclusion, the BCR-ABL mRNA level was useful for monitoring the clinical course in 26 patients with CML. PMID- 22037272 TI - Retroperitoneoscopic nephrectomy for treatment of a case of left single ectopic ureter accompanied by dysplastic kidney. AB - We report the case of a 7-year-old girl with a single ectopic ureter who was treated with retroperitoneoscopic nephrectomy for a chief complaint of urinary incontinence. Preoperative CT showed a contrasted dysplastic kidney of 1cm in the renal fossa and a left ureteral opening into the vagina. Retroperitoneoscopic left nephrectomy was conducted with opening of the lateroconal fascia to enable identification of the dysplastic kidney. No intraoperative complications were encountered. Urinary incontinence improved immediately after surgery. This case shows that a retroperitoneal approach can be used in nephrectomy if the position of the kidney can be determined preoperatively. PMID- 22037273 TI - A case of renal transcatheter arterial embolization with ethanol in autosomal dominant polycystic kidney disease for volume reduction. AB - We report herein the case of a 76-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) and chronic renal failure resulting in intractable abdominal distension and anorexia. Computed tomography (CT) showed enlarged and cystic kidneys. We performed transcatheter arterial embolization (TAE) for renal arteries with ethanol. Absolute ethanol with iodinated contrast medium or Lipiodol was delivered into both renal arteries. The patient's low grade fever subsided in 5 days, and no other complication occurred. The sensation of abdominal distension diminished approximately 1 month after embolization. A progressive decrease in kidney size was observed soon after embolization. The percentage of the decrement of kidney size was approximately 50% after 17 months. These results indicate that renal TAE with ethanol is a safe, cost-effective, and minimally invasive technique to reduce kidney size in symptomatic ADPKD patients. PMID- 22037275 TI - Multidsciplinary heart failure management and end of life care. AB - PURPOSE OF REVIEW: There has been much improvement in the treatment of heart failure over the past decade through the implementation of a multidisciplinary team approach to disease management focused on optimizing medication, the application of device-based therapy, surgical intervention and in promoting the education of patients and carers in self-management. This multidisciplinary strategy has now been extended to try and improve the care of those with advanced heart failure in the latter phases of the disease trajectory nearing the end of their lives. RECENT FINDINGS: A growing consensus has emerged in the literature that confirms the need to extend multidisciplinary management beyond the early targets of reducing heart failure-related mortality and morbidity to address the significant care needs of those who decline due to the often inexorable progression of this syndrome. Multidisciplinary management facilitates the development of a comprehensive care plan that is specifically tailored to accommodate the requirements of individual patients and their families and fosters a collaborative approach to care to optimize symptom management, avoid potential treatments conflicts, and to fulfil their supportive care needs. Partnership working between the three principal clinical disciplines of cardiology, specialist palliative care and general practice is central to this process and promotes coordinated care across hospital, hospice and community based services. SUMMARY: Advanced heart failure management has improved over time; however, the incorporation of a multidisciplinary care model appears to offer significant promise in dealing with complex care needs of heart failure patients towards the end of life. Delivery of this practice requires the development of bespoke care structures that are relevant to the spectrum of healthcare service environments. PMID- 22037276 TI - Improved prediction of all-cause mortality by a combination of serum total testosterone and insulin-like growth factor I in adult men. AB - OBJECTIVE: Lower levels of anabolic hormones in older age are well documented. Several studies suggested that low insulin-like growth factor I (IGF-I) or testosterone levels were related to increased mortality. The aim of the present study was to investigate the combined influence of low IGF-I and low testosterone on all-cause mortality in men. METHODS AND RESULTS: From two German prospective cohort studies, the DETECT study and SHIP, 3942 men were available for analyses. During 21,838 person-years of follow-up, 8.4% (n=330) of men died. Cox model analyses with age as timescale and adjusted for potential confounders revealed that men with levels below the 10th percentile of at least one hormone [hazard ratio (HR) 1.38 (95% confidence-interval (CI) 1.06-1.78), p=0.02] and two hormones [HR 2.88 (95% CI 1.32-6.29), p<0.01] showed a higher risk of all-cause mortality compared to men with non-low hormones. The associations became non significant by using the 20th percentile as cut-off showing that the specificity increased with lower cut-offs for decreased hormone levels. The inclusion of both IGF-I and total testosterone in a mortality prediction model with common risk factors resulted in a significant integrated discrimination improvement of 0.5% (95% CI 0.3-0.7%, p=0.03). CONCLUSIONS: Our results prove that multiple anabolic deficiencies have a higher impact on mortality than a single anabolic deficiency and suggest that assessment of more than one anabolic hormone as a biomarker improve the prediction of all-cause mortality. PMID- 22037277 TI - Ten new withanolides from Physalis peruviana. AB - Ten new withanolides, including four perulactone-type withanolides, perulactones E-H (1-4), three 28-hydroxy-withanolides, withaperuvins I-K (5-7), and three other withanolides, withaperuvins L-N (8-10), together with six known compounds (11-16) were isolated from the aerial parts of Physalis peruviana. The structures of these compounds were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, IR, HR-MS) and chemical methods. PMID- 22037278 TI - Physical properties of SrSn(4) single crystals. AB - We present detailed thermodynamic and transport measurements on single crystals of the recently discovered binary intermetallic superconductor, SrSn(4). We find this material to be a slightly anisotropic three-dimensional, strongly coupled, possibly multiband, superconductor. Hydrostatic pressure causes a decrease in the superconducting transition temperature at the rate of ~ - 0.068 K kbar(-1). Band structure calculations are consistent with experimental data on the Sommerfeld coefficient and upper superconducting critical field anisotropy, and suggest a complex, multi-sheet Fermi surface formed by four bands. PMID- 22037279 TI - Internal jugular vein duplication: a further truncular malformation in a patient with multiple sclerosis. AB - Different internal jugular vein (IJV) abnormalities can be found in patients with multiple sclerosis (MS): stenoses, complete occlusion, distortions and intraluminal structures, such as membranes, webs and inverted valves. IJV duplication is a very rare phenomenon. We report a case of right IJV duplication as an incidental finding during IJV morphological and haemodynamic assessment in a patient with MS. A 55-year-old female patient was admitted to our Institute for IJV and vertebral veins morphological and haemodynamic assessment. During the last seven years she had been treated for MS. Colour Doppler ultrasonography in our patient did not reveal IJV or vertebral veins stenoses or abnormal valves, but instead right IJV duplication. This finding was confirmed using multislice computed tomography angiography and by selective phlebography. In conclusion, to our knowledge, a case of IJV duplication in a patient with MS has not been described yet. This further venous malformation can be assessed by the means of Doppler ultrasounds. PMID- 22037280 TI - Preoperative determination of anatomic variations of the small saphenous vein for varicose vein surgery by three-dimensional computed tomography venography. AB - OBJECTIVE: To define the anatomical variations of small saphenous vein (SSV) for varicose vein (VV) surgery by three-dimensional computed tomography venography (3D-CTV) and to analyse the impact of this preoperative evaluation on surgical outcomes. METHODS: A total of 120 consecutive limbs with SSV insufficiency having undergone VV surgery from January 2005 until December 2007 were enrolled. The medical records and images were analysed retrospectively. RESULTS: The relationship between SSV and gastrocnemial vein (GNV) were categorized into two: (a) SSV and GNV drained to popliteal vein (PV) separately (100 limbs, 87%) and (b) SSV and GNV made common channel which drained to PV (15 limbs, 13%). Saphenopopliteal junction morphology was normal (75 limbs), severe tortuosity near PV (19 limbs), ampullary ectasia (4 limbs) and duplicated drainage to PV (2 limbs). No recurrence of VV was noted. CONCLUSIONS: CTV can provide thorough preoperative anatomic information of the SSV variations and reduce the recurrence of VV. PMID- 22037281 TI - Is endovenous laser ablation possible while taking warfarin? AB - PURPOSE: The subgroup of patients with venous ulcers requiring anticoagulation for co-morbid conditions has traditionally created a therapeutic dilemma. Perioperative management of anticoagulation can be costly and increase the risk of surgical complications. This group of patients is often elderly and shows poor compliance with compression hosiery. The aim of this study was to investigate the outcome of endovenous laser ablation (EVLA) of the great saphenous vein (GSV) in patients remaining on therapeutic anticoagulation. MATERIALS AND METHODS: Fifteen consecutive patients (CEAP [clinical, aetiological, anatomical and pathological elements] classification 5 or 6) were treated with standard GSV EVLA using tumescent anaesthesia and a diode 1470-nm radial laser fibre while maintaining international normalized ratio at therapeutic levels. Clinical and duplex follow up at six weeks and three, six and 12 months were performed. RESULTS: The GSV was successfully occluded in 14/15 (93%) of patients. The remaining patient had a second successful treatment three months later. No significant complications requiring intervention were encountered. CONCLUSION: EVLA using the diode 1470-nm radial fibre is efficacious with minimal complications in patients therapeutically anticoagulated. This treatment should be added to the armamentarium in this problematic patient group. PMID- 22037282 TI - Chemerin induces CCL2 and TLR4 in synovial fibroblasts of patients with rheumatoid arthritis and osteoarthritis. AB - INTRODUCTION: Chemerin stimulates migration of leukocytes to sites of inflammation and also increases inflammatory signaling in chondrocytes suggesting a function of chemerin in joint inflammation. Synovial fibroblasts (SF) are critically involved in synovitis and subsequent cartilage destruction. Here, we analyzed whether synovial fibroblasts express chemerin and its receptor CMKLR1. Further, the role of chemerin in synovial fibroblast chemotaxis, proliferation, insulin response and release of inflammatory proteins was studied. METHODS: Synovial tissue sections were labeled with chemerin antibody and chemerin was measured in synovial fluid by ELISA. Chemerin mRNA and protein as well as CMKLR1 expression were determined in SFs from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Effects of chemerin on cytokines, chemokines and matrix metalloproteinases (MMP), and on proliferation, migration and insulin signaling were analyzed appropriately. RESULTS: SFs expressed CMKLR1 and chemerin mRNA, and chemerin protein was found in cell supernatants of synovial fibroblasts. Immunohistochemistry detected chemerin in synovial tissue predominantly localized within the lining layer. Chemerin was present in synovial fluids of RA, OA and psoriatic arthritis patients in similar concentrations. Chemerin neither increased IL-6 levels nor MMP-2 or -9 activity in SFs. Also, it did not act as a chemoattractant for these cells. With respect to intracellular signaling, neither basal nor insulin-mediated phosphorylation of Akt was affected. However, chemerin significantly increased TLR4 mRNA and synthesis of CCL2 in SFs while CCL4 and -5 were not altered. Cell proliferation of SFs, however, was modestly reduced by chemerin. CONCLUSIONS: These data show that human SFs express both chemerin and its receptor. As chemerin enhanced expression of TLR4 and induced release of CCL2 in SFs, a role of this protein in innate immune system-associated joint inflammation is proposed. PMID- 22037283 TI - Small volume resuscitation with 7.5% hypertonic saline, hydroxyethyl starch 130/0.4 solution and hypertonic sodium chloride hydroxyethyl starch 40 injection reduced lung injury in endotoxin shock rats: comparison with saline. AB - BACKGROUND: The aim of this study was to investigate the effects of small volume resuscitation with 7.5% hypertonic sodium chloride (HSS), hydroxyethyl starch 130/0.4 solution (HES), and hypertonic sodium chloride hydroxyethyl starch 40 injection (HSH) on endotoxin shock rat lung. METHODS: Thirty Sprague-Dawley (SD) rats were divided randomly into 5 groups ,Group C (negative control group), Group E (lipopolysaccharide, LPS +4 ml/kg saline), Group HSS (LPS +4 ml/kg HSS), Group HES (LPS +4 ml/kg HES) and Group HSH (LPS +4 ml/kg HSH). Endotoxin shock model of rat was produced by injection with LPS. Then small volume resuscitation with different fluids was implemented in each group, respectively. RESULTS: Compared to Group C(negative control group), lung injury in the other four groups was increased. Compared to Group E(LPS +4 ml/kg normal saline), lung injury of Group HSS(LPS +4 ml/kg HSS), HES(LPS +4 ml/kg HES), and HSH (LPS +4 ml/kg HSH)was lessened. Compared to Group C, oxygenation index in Groups E, HSS, HES, and HSH were decreased (P < 0.01). Compared to Group E, oxygenation indexes in Groups HSS, HES, and HSH were significantly increased (P < 0.01). Data of tumor necrosis factor (TNF)-alpha of lung tissue had similar results. However, protein concentration of bronchoalveolar lavage fluid and hydrogen sulfide (H(2)S) concentration indicated contrary results. CONCLUSION: Small volume resuscitation with 7.5% hypertonic sodium chloride, hydroxyethyl starch 130/0.4 solution, and hypertonic sodium chloride hydroxyethyl starch 40 injection could lessen lung injury caused by lipopolysaccharide. And this effect had relation to change of TNF-alpha and H(2)S. PMID- 22037284 TI - Management of dominant upper extremity injuries: a survey of practice patterns. AB - STUDY DESIGN: Internet survey. PURPOSE: To describe current practice patterns in hand therapy to 1) gain insights into beliefs of certified hand therapists (CHTs) related to initiating a hand dominance transfer, 2) describe CHTs' clinical decision-making strategies, and 3) describe research priorities related to hand dominance transfer in hand therapy. PARTICIPANTS: Five hundred sixty-three members of the American Society of Hand Therapists. METHODS: The online Internet survey contained 30 questions related to four categories: 1) demographics of clinicians, 2) beliefs about hand dominance transfer, 3) clinical strategies and decision making, and 4) a research agenda related to hand dominance transfer. Data were sorted, compiled, and analyzed descriptively. RESULTS: Respondents were primarily occupational therapists working as full-time staff therapists treating between nine and 15 patients per day with orthopedic injuries to the dominant upper extremity caused by trauma. The overwhelming majority of respondents (92.7%) believed that motivation is a factor in the success of the hand dominance transfer. Most respondents (83%) do not directly initiate a hand dominance transfer. The number one reason (64%) for not initiating a dominance transfer is that CHTs believe that their patients will regain full recovery of injured hand over time. If a transfer is initiated, the number one task addressed is handwriting (62%); the most commonly recommended piece of adaptive equipment was the handsfree can opener (63.8%); 72% educate on the risk of overuse injury to the noninjured (intact) limb. Most respondents agreed or strongly agreed that more research needs to be done related to hand dominance transfer, specifically related to return to work rates, interventions using virtual reality, and assessments using neuroimaging technologies. LEVEL OF EVIDENCE: 3b. PMID- 22037285 TI - L-pGlu-(2-propyl)-L-His-L-ProNH2 attenuates 4-aminopyridine-induced epileptiform activity and sodium current: a possible action of new thyrotropin-releasing hormone analog for its anticonvulsant potential. AB - L-PGlu-(2-propyl)-L-His-L-ProNH2 (NP-647) is a CNS active thyrotropin-releasing hormone (TRH) analog with potential application in various CNS disorders including seizures. In the present study, mechanism of action for protective effect of NP-647 was explored by studying role of NP-647 on epileptiform activity and sodium channels by using patch-clamp methods. Epileptiform activity was induced in subicular pyramidal neurons of hippocampal slice of rat by perfusing 4 aminopyridine (4-AP) containing Mg+2-free normal artificial cerebrospinal fluid (nACSF). Increase in mean firing frequency was observed after perfusion of 4-AP and zero Mg+2 (2.10+/-0.47 Hz) as compared with nACSF (0.12+/-0.08 Hz). A significant decrease in mean firing frequency (0.61+/-0.22 Hz), mean frequency of epileptiform events (0.03+/-0.02 Hz vs. 0.22+/-0.05 Hz of 4-AP+0 Mg), and average number of action potentials in paroxysmal depolarization shift-burst (2.54+/-1.21 Hz vs. 8.16+/-0.88 Hz of 4-AP+0 Mg) was observed. A significant reduction in peak dV/dt (246+/-19 mV ms-1 vs. 297+/-18 mV ms-1 of 4-AP+0 Mg) and increase (1.332+/ 0.018 ms vs. 1.292+/-0.019 ms of 4-AP+0 Mg) in time required to reach maximum depolarization were observed indicating role of sodium channels. Concentration dependent depression of sodium current was observed after exposure to dorsal root ganglion neurons to NP-647. NP-647 at different concentrations (1, 3, and 10 MUM) depressed sodium current (15+/-0.5%, 50+/-2.6%, and 75+/-0.7%, respectively). However, NP-647 did not show change in the peak sodium current in CNa18 cells. Results of present study demonstrated potential of NP-647 in the inhibition of epileptiform activity by inhibiting sodium channels indirectly. PMID- 22037286 TI - The role of eIF5A in protein synthesis. PMID- 22037287 TI - Pleomorphic lobular carcinoma in situ: treatment options for a new pathologic entity. PMID- 22037288 TI - NAC transcription factors in plant abiotic stress responses. AB - Abiotic stresses such as drought and high salinity adversely affect the growth and productivity of plants, including crops. The development of stress-tolerant crops will be greatly advantageous for modern agriculture in areas that are prone to such stresses. In recent years, several advances have been made towards identifying potential stress related genes which are capable of increasing the tolerance of plants to abiotic stress. NAC proteins are plant-specific transcription factors and more than 100 NAC genes have been identified in Arabidopsis and rice to date. Phylogenetic analyses indicate that the six major groups were already established at least in an ancient moss lineage. NAC transcription factors have a variety of important functions not only in plant development but also in abiotic stress responses. Stress-inducible NAC genes have been shown to be involved in abiotic stress tolerance. Transgenic Arabidopsis and rice plants overexpressing stress-responsive NAC (SNAC) genes have exhibited improved drought tolerance. These studies indicate that SNAC factors have important roles for the control of abiotic stress tolerance and that their overexpression can improve stress tolerance via biotechnological approaches. Although these transcription factors can bind to the same core NAC recognition sequence, recent studies have demonstrated that the effects of NAC factors for growth are different. Moreover, the NAC proteins are capable of functioning as homo- or hetero-dimer forms. Thus, SNAC factors can be useful for improving stress tolerance in transgenic plants, although the mechanism for mediating the stress tolerance of these homologous factors is complex in plants. Recent studies also suggest that crosstalk may exist between stress responses and plant growth. This article is part of a Special Issue entitled: Plant gene regulation in response to abiotic stress. PMID- 22037289 TI - Validation of surface plasmon resonance screening of a diverse chemical library for the discovery of protein tyrosine phosphatase 1b binders. AB - We investigated the suitability of surface plasmon resonance (SPR) for providing quantitative binding information from direct screening of a chemical library on protein tyrosine phosphatase 1b (PTP1B). The experimental design was established from simulations to detect binding with K(D) < 10-4 M. The 1120 compounds (cpds) were injected sequentially at concentrations [C(cpd)] of 0.5 or 10 MUM over various target surfaces. An optimized evaluation procedure was applied. More than 90% of cpds showed no detectable signal in four screens. The 30 highest responders at C(cpd)=10 MUM, of which 25 were selected in at least one of three screens at C(cpd)=0.5 MUM, contained 22 promiscuous binders and 8 potential PTP1B specific binders with K(D) ~10-5 M. Inhibition of PTP1B activity was assayed and confirmed for 6 of these, including sanguinarine, a known PTP1B inhibitor. C(cpd) dependence studies fully confirmed screening conclusions. The quantitative consistency of SPR data led us to propose a structure-activity relationship (SAR) model for developing selective PTP1B inhibitors based on the ranking of 10 arylbutylpiperidine analogs. PMID- 22037290 TI - Domain-based assays of individual antibody concentrations in an oligoclonal combination targeting a single protein. AB - Quantitation of individual monoclonal antibodies (mAbs) within a combined antibody drug product is required for preclinical and clinical drug development, including pharmacokinetic (PK), toxicology, stability, and biochemical characterization studies of such drugs. We have developed an antitoxin, XOMA 3AB, consisting of three recombinant mAbs that potently neutralize the known subtypes of type A botulinum neurotoxin (BoNT/A). The three mAbs bind nonoverlapping BoNT/A epitopes with high affinity. XOMA 3AB is being developed as a treatment for botulism resulting from BoNT/A. To develop antibody-specific assays, we cloned, expressed, and purified BoNT/A domains from Escherichia coli. Each mAb bound only to its specific domain with affinity comparable to the binding to holotoxin. mAb-specific domains were used to develop an enzyme-linked immunosorbent assay (ELISA) for characterization of the integrity and binding activity of the three mAbs in the drug product. An electrochemiluminescence bridging assay that is robust to interference from components in serum was also developed, and we demonstrate that it can be used for PK assays. This type of antigen engineering to generate mAb-specific domains is a general method allowing quantitation and characterization of individual mAbs in a mAb cocktail that binds the same protein and is superior to anti-idiotype approaches. PMID- 22037291 TI - One-step casting of Laemmli discontinued sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel. AB - A modified Laemmli sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) protocol is described. The new method saves 30 min for gel casting without loss of the resolution power of Laemmli gel. In this method, both the upper and lower gels can be cast at the same time because the lower gel contains 10% glycerol, which generates higher density in the lower gel than in the upper gel. PMID- 22037292 TI - Assay of acetylcholinesterase activity by potentiometric monitoring of acetylcholine. AB - An acetylcholine-selective electrode based on a plasticized polymeric membrane has been developed. The electrode exhibited good selectivity for acetylcholine (ACh) over choline and some common ions, low drift, and a fast response to ACh. The response was linear over an ACh concentration range of 1*10(-6) to 1*10(-3) M with a slope of 59.1+/-0.1 and a detection limit of 1.5*10(-7)+/-1.2*10(-8) M. The electrode was used to monitor enzymatic ACh hydrolysis catalyzed by acetylcholinesterase (AChE) at different substrate and enzyme concentrations. A kinetic data analysis permitted the determination of the Michaelis-Menten constant of the enzymatic hydrolysis and AChE activity in the range of 2*10(-5) to 3.8*10(-1)U ml(-1). PMID- 22037293 TI - A spectrophotometric assay for the detection of fungal peroxygenases. AB - Rapid and simple spectrophotometric methods are required for the unambiguous detection of recently discovered fungal peroxygenases in vivo and in vitro. This paper describes a peroxygenase-specific assay using 5-nitro-1,3-benzodioxole as substrate. The product, 4-nitrocatechol, produces a yellow color at pH 7, which can be followed over time at 425 nm (epsilon(425)=9,700 M(-1) cm(-1)), and a red color when adjusted to pH >12, which can be measured in form of an end-point determination at 514 nm (epsilon(514)=11,400 M(-1) cm(-1)). The assay is suitable for detecting peroxygenase activities in complex growth media and environmental samples as well as for high-throughput screenings. PMID- 22037294 TI - Capillary electrophoresis-laser-induced fluorescence (CE-LIF) assay for measurement of intracellular D-serine and serine racemase activity. AB - An enantioselective capillary electrophoresis-laser-induced fluorescence (CE-LIF) method for the analysis of D-serine (D-Ser) in cellular matrices has been developed. The assay involves derivatization with FITC followed by CE-LIF using 0.5 mM hydroxyl propyl-beta-cyclodextrin in borate buffer [80 mM, pH 9.3]. The method was able to resolve D-Ser and L-Ser with an enantioselectivity (alpha) of 1.03 and a resolution (R(s)) of 1.37. Linearity was established from 0.25 to 100.00 MUM. The assay was also able to enantioselectively resolve 6 additional amino acid racemates. The method was applied to the determination of intracellular D-Ser concentrations in PC-12, C6, 1312N1, and HepG2 cell lines. This method was used to determine the concentration-dependent increases in D-Ser and associated EC50 values produced by L-Ser and the concentration-dependent decreases in d-Ser and associated IC50 values produced by glycine, a competitive inhibitor of serine racemase (SR). Western blot analysis determined that the PC 12 and C6 cell lines contained monomeric and dimeric forms of SR while the 1321N1 and HepG2 cells contained only the monomeric form. Although the SR dimer has been identified as the active form of the enzyme, all four of the tested cell lines expressed enzymatically active SR. PMID- 22037295 TI - Determination of estrogens in human urine by high-performance liquid chromatography/diode array detection with ultrasound-assisted cloud-point extraction. AB - A novel and efficient analytical methodology is proposed for extracting and preconcentrating three kinds of estrogens (17beta-estradiol (betaE2), estrone (E1), and diethylstilbestrol (DES)) in human urine prior to high-performance liquid chromatography (HPLC) analysis. It is based on the induction of micellar organized medium by using a nonionic surfactant (Tergitol TMN-6) to extract the target estrogens. Ultrasound was applied to enhance the extraction efficiency. Parameters affecting the extraction of target analytes including the concentration of surfactant, temperature, extraction time, sample pH, ionic strength, and centrifuging time were investigated. Under the optimum conditions, the linear range of betaE2, E1, and DES was from 5.0 to 1000 ng/ml. All correlation coefficients of the calibration curves were higher than 0.997. The relative standard deviations (RSD, n=5) were 2.36-5.27% and the limits of detection (LOD) were 0.1, 0.2, and 0.1 ng/ml for betaE2, E1, and DES in human urine, respectively. The results indicated that the method was successfully applied for analyzing betaE2, E1, and DES in human urine. PMID- 22037297 TI - Operating on a stretcher: a cost analysis. PMID- 22037296 TI - Masticatory performance in older subjects with varying degrees of tooth loss. AB - OBJECTIVES: The purpose of this study was to establish the factors influencing the masticatory performance of older subjects with varying degrees of tooth loss and associated numbers of posterior occlusal contacts. METHODS: The subjects consisted of 1274 independently living people aged 60 years and over. Individuals with partially or fully edentulous arches without a denture replacement or those having any symptoms related to an oral problem were excluded from the study participants. Masticatory performance, maximal occlusal force and stimulated whole saliva were measured. Subjects were grouped into three categories by posterior occlusal contact, according to the Eichner Index. Group A had contacts in four support zones; group B had one to three zones of contact or contact in the anterior region only; and group C had no support zones at all, although a few teeth could still remain. RESULTS: The masticatory performance in groups B and C was found to be 81% and 50% of that of group A, respectively. The multiple linear regression analysis showed that in all the groups, occlusal force was significantly associated with masticatory performance. In groups A and B, the number of residual teeth was significantly associated with masticatory performance, whereas in group C, it had no significant relationship with masticatory performance. Salivary flow rate had a significant correlation with masticatory performance only in group C. CONCLUSIONS: Declines in occlusal contact, occlusal force and salivary flow appear to be associated with reduction of masticatory performance in older adults. However, the crucial factors for masticatory performance varied, depending on the phase of occlusal collapse. PMID- 22037298 TI - Three-dimensional quantitative comparative analysis of trapezial-metacarpal joint surface curvatures in human populations. AB - PURPOSE: Trapezial-metacarpal (TM) joint surfaces appear to be shallower in Asian than in white postmortem specimens, and the frequency of TM osteoarthritis seems to be substantially lower in Asian TM joints. This study tested the hypothesis that there are significant differences among human populations in TM joint surface curvature and that populations of Asian descent have less curvature than those of recent European descent. METHODS: The sample included trapeziums and first metacarpals from skeletons of 80 individuals of recent European and Asian descent and from skeletons of 34 African and 9 Australian aboriginal individuals. We scanned the surfaces using a laser digitizer to generate 3-dimensional models of each articular surface. We calculated dorsovolar, radioulnar, and root mean square curvatures by fitting modeled quadric surfaces to the TM joint surfaces. We tested pairwise comparisons of mean curvatures between populations for statistical significance using a standard resampling method (ie, bootstrapping). We also made pairwise comparisons of mean curvatures between males and females for a combined African and European sample. RESULTS: Mean dorsovolar metacarpal curvature was significantly higher in the European sample than in the Asian, African, and Australian samples. Mean root mean square curvature of the trapezial surface was significantly higher in the European sample than in the Asian sample. The European sample had the highest root mean square and dorsovolar trapezial curvatures of all the populations. We found no significant differences between male and female specimens. CONCLUSIONS: A tendency toward higher mean dorsovolar curvature of both the metacarpal and trapezial surface in the European sample may help to explain the higher frequency of TM osteoarthritis reported in Europeans. CLINICAL RELEVANCE: The greater TM curvatures affect basal thumb joint mechanics in thumb opposition and therefore may be a factor in the development of osteoarthritis at this joint in Europeans. PMID- 22037299 TI - Non-locked and locked plating technology for hand fractures. PMID- 22037300 TI - Epitendinous suture techniques in extensor tendon repairs--an experimental evaluation. AB - PURPOSE: The tension-band principle might be relevant to extensor tendon repairs, and a dorsal-only Silfverskiold epitendinous repair is stronger and stiffer than more conventional techniques in vitro. We aimed to evaluate the strength and stiffness of the strongest epitendinous sutures described, using an in vitro model that subjects the repair to angular force over a pulley, thereby creating a tension-band model. METHODS: Silfverskiold dorsal-only epitendinous extensor tendon repairs in porcine foot tendons (n = 8) were compared to reverse (buried) Silfverskiold (n = 8), Halsted (n = 8), and interrupted horizontal mattress (IHM) repairs (n = 6) in vitro with a tensiometer around a 45 degrees pulley. Thirty tendons total were tested to assess the force required for 2-mm gapping and ultimate tensile strength. RESULTS: The IHM repair had a significantly higher ultimate tensile strength (43 N; SD, 10 N) than the other repairs, which had strengths between 27 N (SD, 4 N) and 31 N (SD, 7 N). The IHM was also significantly more resistant to gapping than the Silfverskiold and Halsted repairs. CONCLUSIONS: Interlocking horizontal mattress, dorsal-only extensor tendon repairs were significantly stronger and more resistant to gapping than Silfverskiold and Halsted repairs. Other repairs were still strong and resistant to gapping in comparison to previously published data for conventional repairs. CLINICAL RELEVANCE: The IHM is a relatively difficult technique to perform, and it remains to be seen whether the additional strength translates to clinical benefits over the easier Silfverskiold technique. PMID- 22037301 TI - Osteoporosis and upper extremity fragility fractures. PMID- 22037303 TI - Metacontrast masking with texture-defined second-order stimuli. AB - We examine metacontrast masking with texture-defined second-order stimuli. Our results reveal that (1) the monotonic type A as well as the nonmonotonic (U shaped) type B metacontrast effect, which has been extensively examined with first-order luminance-defined stimuli, can be obtained with texture-defined second-order stimuli; and (2) while variations of luminance contrast are known to affect the magnitude of metacontrast with first-order stimuli, neither the size nor orientation contrast between texture elements defining the second-order stimuli have a significant impact on the magnitude or shape of metacontrast. These findings bear on theories of metacontrast masking by showing that the mechanism giving rise to nonmonotonic masking effects can operate beyond the level of first-order stimulus processing. PMID- 22037304 TI - The role of local features in shape discrimination of contour- and surface defined radial frequency patterns at low contrast. AB - Shape processing involves a progression from local to global analysis. A key aspect of this is the binding of distributed local features into an overall form followed by the extraction of the shape independently of its local contrast and spatial scales, so enabling the shape to be encoded based on its proportions without reference to its exact size or retinal location. Here we use contour- and surface-defined radial frequency (RF) patterns in a shape discrimination task, previously thought to reflect a global processing stage that has reached contrast and scale invariance. We compare performance across different spatial scales for a wide range of RF patterns (contour spatial frequencies of 0.7-10.0cpd, pattern radii of 0.5-10.5 degrees ), and sharp- and smooth-edged surface-RF patterns, all at low contrast (5* detection threshold). We show that shape discrimination thresholds for RF patterns have a complex series of dependencies on stimulus size (radius), contour spatial frequency (thickness) and contrast, with no scale invariance. Our results are at odds with earlier work showing no effect of radius and spatial frequency on discrimination thresholds. We show that this discrepancy can be accounted for by a differential effect of contrast on shape discrimination, with shape invariance only stabilizing at higher contrasts (10 20* threshold). PMID- 22037302 TI - The 26S proteasome complex: an attractive target for cancer therapy. AB - The 26S proteasome complex engages in an ATP-dependent proteolytic degradation of a variety of oncoproteins, transcription factors, cell cycle specific cyclins, cyclin-dependent kinase inhibitors, ornithine decarboxylase, and other key regulatory cellular proteins. Thus, the proteasome regulates either directly or indirectly many important cellular processes. Altered regulation of these cellular events is linked to the development of cancer. Therefore, the proteasome has become an attractive target for the treatment of numerous cancers. Several proteasome inhibitors that target the proteolytic active sites of the 26S proteasome complex have been developed and tested for anti-tumor activities. These proteasome inhibitors have displayed impressive anti-tumor functions by inducing apoptosis in different tumor types. Further, the proteasome inhibitors have been shown to induce cell cycle arrest, and inhibit angiogenesis, cell-cell adhesion, cell migration, immune and inflammatory responses, and DNA repair response. A number of proteasome inhibitors are now in clinical trials to treat multiple myeloma and solid tumors. Many other proteasome inhibitors with different efficiencies are being developed and tested for anti-tumor activities. Several proteasome inhibitors currently in clinical trials have shown significantly improved anti-tumor activities when combined with other drugs such as histone deacetylase (HDAC) inhibitors, Akt (protein kinase B) inhibitors, DNA damaging agents, Hsp90 (heat shock protein 90) inhibitors, and lenalidomide. The proteasome inhibitor bortezomib is now in the clinic to treat multiple myeloma and mantle cell lymphoma. Here, we discuss the 26S proteasome complex in carcinogenesis and different proteasome inhibitors with their potential therapeutic applications in treatment of numerous cancers. PMID- 22037305 TI - TRP channel gene expression in the mouse retina. AB - In order to identify candidate cation channels important for retinal physiology, 28 TRP channel genes were surveyed for expression in the mouse retina. Transcripts for all TRP channels were detected by RT-PCR and sequencing. Northern blotting revealed that mRNAs for 12 TRP channel genes are enriched in the retina. The strongest signals were observed for TRPC1, TRPC3, TRPM1, TRPM3, and TRPML1, and clear signals were obtained for TRPC4, TRPM7, TRPP2, TRPV2, and TRPV4. In situ hybridization and immunofluorescence revealed widespread expression throughout multiple retinal layers for TRPC1, TRPC3, TRPC4, TRPML1, PKD1, and TRPP2. Striking localization of enhanced mRNA expression was observed for TRPC1 in the photoreceptor inner segment layer, for TRPM1 in the inner nuclear layer (INL), for TRPM3 in the INL, and for TRPML1 in the outer plexiform and nuclear layers. Strong immunofluorescence signal in cone outer segments was observed for TRPM7 and TRPP2. TRPC5 immunostaining was largely confined to INL cells immediately adjacent to the inner plexiform layer. TRPV2 antibodies stained photoreceptor axons in the outer plexiform layer. Expression of TRPM1 splice variants was strong in the ciliary body, whereas TRPM3 was strongly expressed in the retinal pigmented epithelium. PMID- 22037306 TI - Learning to be fast: gain accuracy with speed. AB - Our recent neurophysiological findings provided evidence for collinear facilitation in detecting low-contrast Gabor patches (GPs) and for the abolishment of these collinear interactions by backward masking (BM) (Sterkin et al., 2008; Sterkin, Yehezkel, Bonneh, et al., 2009). We suggested that the suppression induced by the BM eliminates the collinear facilitation. Moreover, our recent study showed that training on a BM task overcomes the BM effect, hence, improves the processing speed (Polat, 2009). Here we applied training on detecting a target that is followed by BM in order to study whether reinforced facilitatory interactions can overcome the suppressive effects induced by BM. Event-Related Potentials (ERPs) were recorded before and after ten training sessions performed on different days. Low-contrast, foveal target GP was simultaneously flanked by two collinear high-contrast GPs. In the BM task, another identical mask was presented at different time-intervals (ISIs). Before training, BM induced suppression of target detection, at the ISI of 50 ms, in agreement with earlier behavioral findings. This ISI coincides with the active time-window of lateral interactions. After training, our results show a remarkable improvement in all behavioral measurements, including percent of correct responses, sensitivity (d'), reaction time (RT) and the decision criterion for this ISI. The ERP results show that before training,BM attenuated the physiological markers of facilitation at the same ISI of 50 ms, measured as the amplitude of the negative N1 peak (latency of 260 ms). After the training, the sensory representation, reflected by P1 peak, has not changed, consistent with the unchanged physical parameters of the stimulus. Instead, the shorter latency (by 20 ms, latency of 240 ms) and the increased amplitude of N1 represent the development of faster and stronger facilitatory lateral interactions between the target and the collinear flankers. Thus, previously effective backward masking became ineffective in disrupting the collinear facilitation. Moreover, a high-amplitude late peak (P4, latency of 610-630 ms) was not affected by training, however its high correlation with RT (95%) before training was significantly decreased (to 76%), consistent with a lower-level representation of a trained skill. We suggest that perceptual learning that strengthens collinear facilitation results in a faster processing speed. PMID- 22037307 TI - Control of Drosophila endocycles by E2F and CRL4(CDT2). AB - Endocycles are variant cell cycles comprised of DNA synthesis (S)- and gap (G) phases but lacking mitosis. Such cycles facilitate post-mitotic growth in many invertebrate and plant cells, and are so ubiquitous that they may account for up to half the world's biomass. DNA replication in endocycling Drosophila cells is triggered by cyclin E/cyclin dependent kinase 2 (CYCE/CDK2), but this kinase must be inactivated during each G-phase to allow the assembly of pre-Replication Complexes (preRCs) for the next S-phase. How CYCE/CDK2 is periodically silenced to allow re-replication has not been established. Here, using genetic tests in parallel with computational modelling, we show that the endocycles of Drosophila are driven by a molecular oscillator in which the E2F1 transcription factor promotes CycE expression and S-phase initiation, S-phase then activates the CRL4(CDT2) ubiquitin ligase, and this in turn mediates the destruction of E2F1 (ref. 7). We propose that it is the transient loss of E2F1 during S phases that creates the window of low Cdk activity required for preRC formation. In support of this model overexpressed E2F1 accelerated endocycling, whereas a stabilized variant of E2F1 blocked endocycling by deregulating target genes, including CycE, as well as Cdk1 and mitotic cyclins. Moreover, we find that altering cell growth by changing nutrition or target of rapamycin (TOR) signalling impacts E2F1 translation, thereby making endocycle progression growth-dependent. Many of the regulatory interactions essential to this novel cell cycle oscillator are conserved in animals and plants, indicating that elements of this mechanism act in most growth-dependent cell cycles. PMID- 22037308 TI - Ecology drives a global network of gene exchange connecting the human microbiome. AB - Horizontal gene transfer (HGT), the acquisition of genetic material from non parental lineages, is known to be important in bacterial evolution. In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence, antibiotic resistance and xenobiotic metabolism to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events. Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human associated bacteria than among ecologically diverse non-human isolates (P = 3.0 * 10(-270)). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases. PMID- 22037309 TI - Somatic retrotransposition alters the genetic landscape of the human brain. AB - Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells, excluding early embryo development and some malignancies. Recent reports of L1 expression and copy number variation in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes. PMID- 22037310 TI - Atomic-resolution dynamics on the surface of amyloid-beta protofibrils probed by solution NMR. AB - Exchange dynamics between molecules free in solution and bound to the surface of a large supramolecular structure, a polymer, a membrane or solid support are important in many phenomena in biology and materials science. Here we present a novel and generally applicable solution NMR technique, known as dark-state exchange saturation transfer (DEST), to probe such exchange phenomena with atomic resolution. This is illustrated by the exchange reaction between amyloid-beta (Abeta) monomers and polydisperse, NMR-invisible ('dark') protofibrils, a process of significant interest because the accumulation of toxic, aggregated forms of Abeta, from small oligomers to very large assemblies, has been implicated in the aetiology of Alzheimer's disease. The (15)N-DEST experiment imprints with single residue-resolution dynamic information on the protofibril-bound species in the form of (15)N transverse relaxation rates ((15)N-R(2)) and exchange kinetics between monomers and protofibrils onto the easily observed two-dimensional (1)H (15)N correlation spectrum of the monomer. The exchanging species on the protofibril surface comprise an ensemble of sparsely populated states where each residue is either tethered to (through other residues) or in direct contact with the surface. The first eight residues exist predominantly in a mobile tethered state, whereas the largely hydrophobic central region and part of the carboxy (C) terminal hydrophobic region are in direct contact with the protofibril surface for a significant proportion of the time. The C-terminal residues of both Abeta40 and Abeta42 display lower affinity for the protofibril surface, indicating that they are likely to be surface exposed rather than buried as in structures of Abeta fibrils, and might therefore comprise the critical nucleus for fibril formation. The values, however, are significantly larger for the C-terminal residues of Abeta42 than Abeta40, which might explain the former's higher propensity for rapid aggregation and fibril formation. PMID- 22037311 TI - Mapping intact protein isoforms in discovery mode using top-down proteomics. AB - A full description of the human proteome relies on the challenging task of detecting mature and changing forms of protein molecules in the body. Large-scale proteome analysis has routinely involved digesting intact proteins followed by inferred protein identification using mass spectrometry. This 'bottom-up' process affords a high number of identifications (not always unique to a single gene). However, complications arise from incomplete or ambiguous characterization of alternative splice forms, diverse modifications (for example, acetylation and methylation) and endogenous protein cleavages, especially when combinations of these create complex patterns of intact protein isoforms and species. 'Top-down' interrogation of whole proteins can overcome these problems for individual proteins, but has not been achieved on a proteome scale owing to the lack of intact protein fractionation methods that are well integrated with tandem mass spectrometry. Here we show, using a new four-dimensional separation system, identification of 1,043 gene products from human cells that are dispersed into more than 3,000 protein species created by post-translational modification (PTM), RNA splicing and proteolysis. The overall system produced greater than 20-fold increases in both separation power and proteome coverage, enabling the identification of proteins up to 105 kDa and those with up to 11 transmembrane helices. Many previously undetected isoforms of endogenous human proteins were mapped, including changes in multiply modified species in response to accelerated cellular ageing (senescence) induced by DNA damage. Integrated with the latest version of the Swiss-Prot database, the data provide precise correlations to individual genes and proof-of-concept for large-scale interrogation of whole protein molecules. The technology promises to improve the link between proteomics data and complex phenotypes in basic biology and disease research. PMID- 22037312 TI - Chitinase from Bacillus licheniformis DSM13: expression in Lactobacillus plantarum WCFS1 and biochemical characterisation. AB - The gene chi, coding for a GH18 chitinase from the Gram-positive bacterium Bacillus licheniformis DSM13 (ATCC 14580), was cloned into the inducible lactobacillal expression vectors pSIP403 and pSIP409, derived from the sakacin-P operon of Lactobacillus sakei, and expressed in the host strain Lactobacillus plantarum WCFS1. Both the complete chi gene including the original bacillal signal sequence as well as the mature chi gene were compared, however, no extracellular chitinase activity was detected with any of the constructs. The chitinase gene was expressed intracellularly as an active enzyme with these different systems, at levels of approximately 5mg of recombinant protein per litre of cultivation medium. Results obtained for the two different expression vectors that only differ in the promoter sequence were well comparable. To further verify the suitability of this expression system, recombinant, His-tagged chitinase Chi was purified from cell extracts of L. plantarum and characterised. The monomeric 65-kDa enzyme can degrade both chitin and chitosan, and shows properties that are very similar to those reported for the native chitinase purified from other B. licheniformis isolates. It shows good thermostability (half lives of stability of 20 and 8.4 days at 37 and 50 degrees C, respectively), and good stability in the pH range of 5-10. The results presented lead the way to overproduction of chitinase in a food-grade system, which is of interest for the food and feed industry. PMID- 22037313 TI - WIP1 enhances tumor formation in a sonic hedgehog-dependent model of medulloblastoma. AB - BACKGROUND: A significant number of medulloblastomas (MBs) originate from abnormal activation of the sonic hedgehog/patched (SHH/PTC) signaling pathway. Although p53 deficiency enhances tumor formation in mice, inactivation of the p53 gene is seen in a minority of MBs. Wild-type p53-induced phosphatase 1 (WIP1) downregulates p53 expression and has been shown to be overexpressed in MBs. OBJECTIVE: We tested the hypothesis that overexpression of WIP1 enhances tumor formation in an SHH-dependent model of MB. METHODS: We used the RCAS/Ntv-a system to study the effect of WIP1 in vitro and in vivo. We transfected A375-TVA cells with RCAS-WIP1 and then exposed these cells to cisplatin to determine the effect on p53 expression. We modeled ectopic WIP1 expression independently and in combination with SHH in the cerebella of newborn mice to assess the effect on tumor formation. Mice were observed for 12 weeks or until neurological symptoms developed. The brains were examined for tumor formation. RESULTS: A375-TVA cells infected with RCAS-WIP1 demonstrated reduced p53 expression after exposure to cisplatin compared with controls. We detected tumors in 12 of 35 mice (34%) injected with RCAS-WIP1 and RCAS-SHH. Tumors were detected in 3 of 40 mice (8%) injected with RCAS-SHH alone. The difference in tumor formation rates was significant (chi(2) test, P = < .01). Tumors did not form in mice injected with RCAS-WIP1 alone. CONCLUSION: We show that ectopic expression of WIP1 cooperates with SHH to enhance formation of MB, although it is insufficient to induce tumors independently. Our results verify the role of WIP1 in MB formation and provide a crucial link to the inactivation of p53 in MBs. PMID- 22037314 TI - Sex disparities in postoperative outcomes after neurosurgical intervention: findings from the UMEND project. AB - BACKGROUND: Little is known about the relationship between sex and the risk of complications after neurosurgical intervention. Improved understanding of this relationship may assist clinicians in advising patients of the risks and benefits of neurosurgical intervention and managing their patients after surgery. OBJECTIVE: To determine the independent relationship between sex and morbidity after neurosurgical intervention. METHODS: Data were collected for 918 neurosurgical cases at the University of Michigan Hospitals. Bivariate chi(2) tests and analysis of variance were used to assess relationships between sex, demographics, case type, medical comorbidities, postoperative complication risk, and postoperative hospital and intensive care unit stay. We fit a multivariable logistic regression model of 30-day complication risk by sex adjusted for potential confounders and used multifactor analysis of variance to assess the relationship between sex and hospital as well as intensive care unit stay, adjusted for potential confounders. RESULTS: The percentages of patients experiencing complications within 30 days of surgery were 20.3% for male and 11.3% for female patients. In multivariable regression models, male sex predicted postoperative complications compared with female sex (odds ratio: 2.0, 95% confidence interval: 1.4-3.0). By multifactor analysis of variance, male sex was associated with longer hospital stay (P < .01), but was not associated with neurosurgical intensive care unit stay. CONCLUSION: Our findings suggest male sex is an independent predictor of postoperative complication risk and increased hospital stay after neurosurgical intervention. This finding may be used clinically to help identify those patients at increased risk of a complicated recovery. Future research might consider mechanisms relating sex and postoperative outcomes. PMID- 22037315 TI - Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells. AB - Mechanisms of digitoxin-inhibited cell growth and induced apoptosis in human non small cell lung cancer (NCI-H460) cells remain unclear. Understanding how digitoxin or derivate analogs induce their cytotoxic effect below therapeutically relevant concentrations will help in designing and developing novel, safer and more effective anti-cancer drugs. In this study, NCI-H460 cells were treated with digitoxin and a synthetic analog D6-MA to determine their anti-cancer activity. Different concentrations of digitoxin and D6-MA were used and the subsequent changes in cell morphology, viability, cell cycle, and protein expressions were determined. Digitoxin and D6-MA induced dose-dependent apoptotic morphologic changes in NCI-H460 cells via caspase-9 cleavage, with D6-MA possessing 5-fold greater potency than digitoxin. In comparison, non-tumorigenic immortalized bronchial and small airway epithelial cells displayed significantly less apoptotic sensitivity compared to NCI-H460 cells suggesting that both digitoxin and D6-MA were selective for NSCLC. Furthermore, NCI-H460 cells arrested in G(2)/M phase following digitoxin and D6-MA treatment. Post-treatment evaluation of key G2/M checkpoint regulatory proteins identified down-regulation of cyclin B1/cdc2 complex and survivin. Additionally, Chk1/2 and p53 related proteins experienced down-regulation suggesting a p53-independent cell cycle arrest mechanism. In summary, digitoxin and D6-MA exert anti-cancer effects on NCI-H460 cells through apoptosis or cell cycle arrest, with D6-MA showing at least 5-fold greater potency relative to digitoxin. PMID- 22037316 TI - A phase II evaluation of lapatinib in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a gynecologic oncology group study. AB - OBJECTIVE: Activation and dimerization of the ERBB family play a role in the pathogenesis and progression of ovarian cancer. We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer (EOC) and to explore the clinical value of expression levels of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER-2/neu, and Ki-67, and the presence of EGFR mutations. METHODS: Eligible patients had recurrent or persistent EOC or primary peritoneal carcinoma, measurable disease, and up to 2 prior chemotherapy regimens for recurrent disease. Patients were treated with lapatinib 1500 mg/day. The primary endpoint of efficacy was 6-month progression free survival (PFS). RESULTS: Twenty-five of 28 patients were eligible and evaluable for analysis of efficacy and toxicity. Two (8.0%) were alive and progression-free at 6 months. No objective responses were observed. There were 1 grade 4 toxicity (fatigue) and few grade 3 toxicities. Associations between Ki-67 with prior platinum-free interval, PFS, and a polymorphism in EGFR were suggested. CONCLUSIONS: Lapatinib has minimal activity in recurrent ovarian cancer. Ki-67 expression may be associated with prior PFS and a polymorphism in EGFR exon 20 (2361G>A, Q787Q). PMID- 22037317 TI - Expression of the opioid growth factor-opioid growth factor receptor axis in human ovarian cancer. AB - OBJECTIVE: The opioid growth factor (OGF) and its receptor (OGFr), serve as inhibitory axis regulating cell proliferation in normal cells and cancer. We investigated the presence and relative expression of OGF and OGFr in normal human ovarian surface epithelial (HOSE) cells, benign ovarian cysts, and ovarian cancers. METHODS: Surgical samples of 16 patients with ovarian cancer and 27 patients with ovarian benign cysts were obtained intraoperatively. HOSE were collected by scraping the surface of normal ovaries of 10 post menopausal women undergoing hysterectomy and oophorectomy. Semiquantitative immunohistochemistry was used to assess the presence, distribution, and levels of OGF and OGFr. Receptor binding assays measured binding capacity and affinity of OGFr for radiolabeled OGF. RESULTS: OGF and OGFr were present in HOSE cells, ovarian cysts, and ovarian cancers. Compared to HOSE cells, OGF and OGFr protein levels were reduced 29% and 34% (p<0.001), respectively, in ovarian cysts, and decreased 58% and 48% (p<0.001), respectively, in ovarian cancers. Binding assays revealed 5.4 fold fewer OGFr binding sites in cancers than cysts (p<0.05). Levels of OGF and OGFr were comparable in primary, metastatic, or recurrent ovarian cancers. CONCLUSION: We have shown that a native opioid pathway, the OGF-OGFr axis, is present in human ovarian cancer. Importantly, the expression of OGF and OGFr is diminished in human ovarian cancer. As OGF and OGFr normally function in maintaining cell proliferation, therapy to harness OGF/OGFr function could provide a useful biologic-based treatment for human ovarian cancer. PMID- 22037319 TI - Dispersion and damping of zone-boundary magnons in the noncentrosymmetric superconductor CePt3Si. AB - Inelastic neutron scattering (INS) is employed to study damped spin-wave excitations in the noncentrosymmetric heavy-fermion superconductor CePt3Si along the antiferromagnetic Brillouin zone boundary in the low-temperature magnetically ordered state. Measurements along the (1/2 1/2 L) and (H H 1/2 - H) reciprocal space directions reveal deviations in the spin-wave dispersion from the previously reported model. The broad asymmetric shape of the peaks in energy signifies strong spin-wave damping by interactions with the particle-hole continuum. Their energy width exhibits no evident anomalies as a function of momentum along the (1/2 1/2 L) direction which could be attributed to Fermi surface nesting effects, implying the absence of pronounced commensurate nesting vectors at the magnetic zone boundary. In agreement with a previous study, we find no signatures of the superconducting transition in the magnetic excitation spectrum, such as a magnetic resonant mode or a superconducting spin gap, either at the magnetic ordering wavevector (0 0 1/2) or at the zone boundary. However, the low superconducting transition temperature in this material still leaves the possibility of such features being weak and therefore hidden below the incoherent background at energies ? 0.1 meV, precluding their detection by INS. PMID- 22037318 TI - Correlation of serum HE4 with tumor size and myometrial invasion in endometrial cancer. AB - OBJECTIVE: To evaluate the utility of serum (HE4) as a marker for high risk disease in patients with endometrial cancer (EC). METHODS: Preoperative serum HE4 levels were measured from a cohort of 75 patients surgically treated for EC. Cases were compared to matched controls without a history of cancer. HE4 levels were analyzed as a function of primary tumor diameter, grade, stage and histological subtype. Wilcoxon rank-sum test, ROC curve, Spearman rank correlation coefficient and contingency tables were used for statistical analyses. RESULTS: Stage distribution was as follows: 49 stage I, 2 stage II, 20 stage III, 4 stage IV. Type I EC was present in 54 patients, type II in 21. Median HE4 was significantly elevated in both types I and II EC compared to controls (P<0.001 and P=0.019, respectively). There was significant correlation between type I EC, median HE4, deep myometrial invasion (MI) (>50%, P<0.001) and primary tumor diameter (PTD) (>2 cm, P=0.002). Low risk patients (type I, MI <= 50% and PTD <= 2 cm) had significantly lower median HE4 compared to all other type I EC patients (P<0.01). In comparison to prior investigations, HE4 (cutoff of 8 mfi) was more sensitive than CA125 in detecting advanced stage disease. CONCLUSION: Our data suggest that HE4 is elevated in a high proportion of EC patients, is correlated with PTD and MI, and is more sensitive than CA125 in EC. These observations suggest potential utility of HE4 in the preoperative prediction of high risk disease and the necessity for definitive surgical staging. PMID- 22037320 TI - Is robotic surgery cost-effective: yes. AB - PURPOSE OF REVIEW: With the expanding use of new technology in the treatment of clinically localized prostate cancer (PCa), the financial burden on the healthcare system and the individual has been important. Robotics offer many potential advantages to the surgeon and the patient. We assessed the potential cost-effectiveness of robotics in urological surgery and performed a comparative cost analysis with respect to other potential treatment modalities. RECENT FINDINGS: The direct and indirect costs of purchasing, maintaining, and operating the robot must be compared to alternatives in treatment of localized PCa. Some expanding technologies including intensity-modulated radiation therapy are significantly more expensive than robotic surgery. Furthermore, the benefits of robotics including decreased length of stay and return to work are considerable and must be measured when evaluating its cost-effectiveness. SUMMARY: Robot assisted laparoscopic surgery comes at a high cost but can become cost-effective in mostly high-volume centers with high-volume surgeons. The device when utilized to its maximum potential and with eventual market-driven competition can become affordable. PMID- 22037322 TI - Community resilience and health: the role of bonding, bridging, and linking aspects of social capital. AB - The current study draws on data from the 2007 and 2009 Citizenship Survey collected in England (n=17,572) to explore the role of social capital in building community resilience and health, using the bonding, bridging, and linking social capital framework of Szreter and Woolcock (2004). The results show that the indicators of the different types of social capital are only weakly interrelated, suggesting that they capture different aspects of the social environment. In line with the expectations, most indicators of bonding, bridging, and linking social capital were significantly associated with neighbourhood deprivation and self reported health. In particular bonding and bridging social cohesion, civic participation, heterogeneous socio-economic relationships, and political efficacy and trust appeared important for community health after controlling for neighbourhood deprivation. However, no support was found for the hypothesis that the different aspects help buffer against the detrimental influences of neighbourhood deprivation. PMID- 22037321 TI - Developing a successful robotics program. AB - PURPOSE OF REVIEW: Advancements in the robotic surgical technology have revolutionized the standard of care for many surgical procedures. The purpose of this review is to evaluate the important considerations in developing a new robotics program at a given healthcare institution. RECENT FINDINGS: Patients' interest in robotic-assisted surgery has and continues to grow because of improved outcomes and decreased periods of hospitalization. Resulting market forces have created a solid foundation for the implementation of robotic surgery into surgical practice. Given proper surgeon experience and an efficient system, robotic-assisted procedures have been cost comparable to open surgical alternatives. Surgeon training and experience is closely linked to the efficiency of a new robotics program. Formally trained robotic surgeons have better patient outcomes and shorter operative times. Training in robotics has shown no negative impact on patient outcomes or mentor learning curves. SUMMARY: Individual economic factors of local healthcare settings must be evaluated when planning for a new robotics program. The high cost of the robotic surgical platform is best offset with a large surgical volume. A mature, experienced surgeon is integral to the success of a new robotics program. PMID- 22037323 TI - Can we trust your data? PMID- 22037324 TI - Reader poses questions regarding article's methodology. PMID- 22037326 TI - A specialist breast care nurse role for women with metastatic breast cancer: enhancing supportive care. PMID- 22037327 TI - Managing families with a hereditary cancer syndrome. PMID- 22037328 TI - Fatigue and physical performance in children and adolescents receiving chemotherapy. AB - PURPOSE/OBJECTIVES: To examine the relationship between physical performance and fatigue in child and adolescent cohorts during the first three cycles of chemotherapy. DESIGN: Prospective, observational design. SETTING: Two pediatric cancer centers in the upper Midwest region of the United States. SAMPLE: 16 children and 14 adolescents newly diagnosed with cancer. METHODS: Standardized instruments were administered during the first and third cycles of chemotherapy. Instruments included physical performance tests (Timed Up and Down Stairs [TUDS] and the 6-Minute Walk Test [6MWT]) and a self-report fatigue scale. MAIN RESEARCH VARIABLES: Fatigue and physical performance. FINDINGS: In the child cohort, physical performance appeared to improve and fatigue diminished from cycle 1 to 3 of chemotherapy. When time on TUDS decreased, fatigue tended to decrease; when 6MWT distance increased, fatigue decreased. In the adolescent cohort, fatigue seemed to decrease but physical performance measures evidenced little change. Correlations between changes in the physical performance variables and fatigue were not significant. CONCLUSIONS: Fatigue may decrease early in treatment as disease symptoms resolve. Fatigue in the child cohort was related to physical performance, which is consistent with previous studies that defined fatigue in children as primarily a physical sensation. Findings in the adolescent cohort support research that defined adolescent fatigue as more complex with mental, emotional, and physical components. IMPLICATIONS FOR NURSING: Knowing how fatigue relates to physical performance in children and adolescents informs the nurse in educating patients and families about symptom management. PMID- 22037329 TI - Implementation of an evidence-based order set to impact initial antibiotic time intervals in adult febrile neutropenia. AB - PURPOSE/OBJECTIVES: To evaluate the impact of the implementation of a standardized order set on the time interval in initiation of antibiotic therapy for adult patients with cancer and febrile neutropenia. DESIGN: Practice change. SETTING: The oncology unit of an urban hospital in the south-eastern United States. SAMPLE: Adult patients with cancer and febrile neutropenia admitted six months prior to (n = 30) or during the three months following (n = 23) implementation of the order set. METHODS: Literature regarding febrile neutropenia, use of order sets, and change process was reviewed. In addition, a retrospective and concurrent chart review was conducted for adult patients admitted with febrile neutropenia. Time intervals were analyzed using SPSS(r) software, version 18. MAIN RESEARCH VARIABLES: Initial antibiotic times, order set use, and length of stay. FINDINGS: An overall reduction in time intervals for initiation of antibiotic therapy was observed for presentation (t = 2.25; degrees of freedom [df] = 37; p = 0.031) and order (t = 2.67; df = 40.17; p = 0.012) to antibiotic administration, with an order-set usage of 31% in the inpatient unit and 71% in the emergency department. CONCLUSIONS: Findings in the presence of low order-set usage suggest that staff education and placement of the order-set antibiotics in unit-based medication dispensing machines helped reduce time intervals for initial antibiotic therapy. IMPLICATIONS FOR NURSING: The use of an evidence-based approach to nursing care is essential to achieving the best outcomes for patients with febrile neutropenia. Incorporation of current evidence into an order set to guide clinical practice and comprehensive nurse, pharmacy, and physician education are needed for the successful implementation of evidence based practice changes. PMID- 22037330 TI - Symptom clusters and quality of life in older adult breast cancer survivors. AB - PURPOSE/OBJECTIVES: To identify symptom clusters in older adult breast cancer survivors (ages 65-97 years) and examine whether symptom clusters are related to demographic, health, and quality-of-life variables. DESIGN: Factor analysis to identify possible symptom clusters. The resulting clusters then were correlated with quality-of-life measures. SETTING: Phone interviews between the participants and a trained research nurse. SAMPLE: 192 breast cancer survivors (X age = 70). METHODS: This was a secondary data analysis of the baseline measures of demographics, health history, symptom bother, and physical, mental, and existential dimensions of quality of life. Exploratory and confirmatory factor analyses were conducted as well as multiple indicator multiple cause modeling and partial correlation analyses to assess the relationships among clusters and demographic, health history, and quality-of-life measures. MAIN RESEARCH VARIABLES: Self-reported symptom bother, demographics such as age and education level, health history, and quality of life. FINDINGS: Seven clinically distinct symptom clusters tapping 36 different symptoms in older adult breast cancer survivors were found. These symptom clusters were significantly related to multiple dimensions of quality of life. CONCLUSIONS: Older adult breast cancer survivors experience multiple concurrent symptoms that appear to cluster. Identifying symptom clusters helps to elucidate possible intersymptom relationships which may lead to the design of more effective symptom management interventions for older adult breast cancer survivors. IMPLICATIONS FOR NURSING: Older adult breast cancer survivors should be assessed for a wide variety of symptoms if clinicians hope to identify and understand intersymptom relationships. Such assessment would enable more comprehensive symptom management. PMID- 22037331 TI - Engaging in medical vigilance: understanding the personal meaning of breast surveillance. AB - PURPOSE/OBJECTIVES: To explore how women with a hereditary risk of breast cancer experience living with and managing that risk through surveillance. RESEARCH APPROACH: Hermeneutic phenomenology guided the qualitative research design. SETTING: The Facing Our Risk of Cancer Empowered online organization. PARTICIPANTS: 9 women undergoing breast surveillance for hereditary breast cancer risk recruited through purposive sampling. METHODOLOGIC APPROACH: Data were collected through semistructured interviews lasting about an hour. A team approach guided data analysis of transcribed interview text based on a modified Diekelman, Allen, and Tanner method. MAIN RESEARCH VARIABLES: Lived experience and personal meaning of hereditary breast cancer risk and surveillance. FINDINGS: Hereditary risk of breast cancer involves a change in one's view of life and necessitates engaging in medical vigilance, often making these women feel ill when they are otherwise healthy. Most have personal family experiences of cancer and value surveillance, although they live with the "what if" of a cancer diagnosis when waiting for surveillance results. All women discussed a need for accurate information, support, and guidance from healthcare providers. CONCLUSIONS: Women became their own experts at living with and managing hereditary breast cancer risk. Experiences and interactions within the healthcare system influenced the meaning of breast surveillance. INTERPRETATION: Nurses should be aware of the high level of knowledge among women living with hereditary risk and respect their knowledge by providing accurate and informed care. That can occur only through proper education of nurses and all healthcare professionals working with women at risk for hereditary breast cancer so that they understand current standards of care and how hereditary breast cancer risk is defined and managed. PMID- 22037332 TI - Ovarian cancer survivors: qualitative analysis of the symptom of sexuality. AB - PURPOSE/OBJECTIVES: To better understand treatment-induced changes in sexuality from the patient perspective, to learn how women manage these changes in sexuality, and to identify what information they want from nurses about this symptom. RESEARCH APPROACH: Qualitative descriptive methods. SETTING: An outpatient gynecologic clinic in an urban area in the southeastern United States served as the recruitment site for patients. PARTICIPANTS: Eight women, ages 33 69, receiving first-line treatment for ovarian cancer participated in individual interviews. Five women, ages 40-75, participated in a focus group and their status ranged from newly diagnosed to terminally ill from ovarian cancer. METHODOLOGIC APPROACH: Both individual interviews and a focus group were conducted. Content analysis was used to identify themes that described the experience of women as they became aware of changes in their sexuality. Triangulation of approach, the researchers, and theory allowed for a rich description of the symptom experience. FINDINGS: Regardless of age, women reported that ovarian cancer treatment had a detrimental impact on their sexuality and that the changes made them feel "no longer whole." Mechanical changes caused by surgery coupled with hormonal changes added to the intensity and dimension of the symptom experience. Physiologic, psychological, and social factors also impacted how this symptom was experienced. CONCLUSIONS: Regardless of age or relationship status, sexuality is altered by the diagnosis and treatment of ovarian cancer. INTERPRETATION: Nurses have an obligation to educate women with ovarian cancer about anticipated changes in their sexuality that may come from treatment. PMID- 22037333 TI - Nurses' perceptions of educational gaps in delivering end-of-life care. AB - PURPOSE/OBJECTIVES: To assess end-of-life (EOL) care core competencies deemed most important with corresponding educational needs from oncology nurses and to describe the characteristics of the respondents that are associated with selection of the top-ranked core competencies. DESIGN: Descriptive, cross sectional study. SETTING: Mailed and online surveys. SAMPLE: 714 members of the Oncology Nursing Society from Georgia, Virginia, Washington, and Wisconsin. METHODS: Responses to a mailed or e-mailed researcher-developed questionnaire during a six-month period were collated and analyzed. MAIN RESEARCH VARIABLES: Ranking of EOL care core competencies and perceived gaps in EOL continuing education. FINDINGS: Almost all of the respondents indicated that EOL care was a part of their practice and that continuing education was important, but more than half of the respondents had fewer than two hours of continuing education regarding EOL care in the past two years. Twenty-five percent of the respondents do not believe they are adequately prepared to effectively care for a dying patient. Symptom management was the top-rated core competency, consistent across age, education level, practice role, and practice setting. How to talk to patients and families about dying and what comprises palliative care also was selected frequently. CONCLUSIONS: Symptom management is the number one core competency, and the quantity and quality of EOL continuing education is inadequate. Educational gaps exist in EOL nursing care. IMPLICATIONS FOR NURSING: Assessing what nurses believe to be leading EOL core competencies is useful in improving educational curricula along with considering characteristics of nurses when planning EOL educational programs. PMID- 22037334 TI - Nurses' use of hazardous drug-handling precautions and awareness of national safety guidelines. AB - PURPOSE/OBJECTIVES: To determine patterns of personal protective equipment (PPE) used by oncology nurses while handling hazardous drugs (HDs) and to assess knowledge of the 2004 National Institute for Occupational Safety and Health (NIOSH) Alert and its effect on precaution use. DESIGN: Descriptive, correlational. SETTING: The Oncology Nursing Society 31st Annual Congress in Boston, MA, in 2006. SAMPLE: 330 nurses who prepared and/or administered chemotherapy. METHODS: Nurses described HD safe-handling precaution use by self report survey. MAIN RESEARCH VARIABLES: The availability and use of biologic safety cabinets and PPE. FINDINGS: Respondents were well educated (57% had a bachelor's degree or more), experienced (X = 19, SD = 10.2 years in nursing and X = 12, SD = 7.9 years in oncology), and certified (70%; majority OCN(r)). Forty seven percent of respondents were aware of the NIOSH Alert. Thirty-five percent of all participants and 93% of nurses in private practice settings reported preparing chemotherapy. Glove use (95%-100%) was higher than that reported in earlier studies, and gown use for drug preparation (65%), drug administration (50%), and handling excretions (23%) have remained unchanged. Double-gloving was rare (11%-18%). Nurses in private practices were less likely to have chemotherapy designated PPE available, use PPE, and use spill kits for HD spills. CONCLUSIONS: Nurses have adopted glove use for HD handling; however, gown use remains comparatively low. Chemotherapy-designated PPE is not always provided by employers. Nurses lack awareness of current safety guidelines. IMPLICATIONS FOR NURSING: Nurses must know about the risks of HD exposure and ways to reduce exposure. Employers must provide appropriate PPE and encourage its use. Alternative methods of disseminating safety recommendations are needed. PMID- 22037335 TI - Measuring oncology nurses' psychosocial care practices and needs: results of an Oncology Nursing Society psychosocial survey. AB - PURPOSE/OBJECTIVES: To develop and implement a survey of Oncology Nursing Society (ONS) members focused on their current practices and needs in relation to providing psychosocial care. DESIGN: Descriptive, cross-sectional. SETTING: Web based survey of ONS members. SAMPLE: An invitation was e-mailed to 11,171 ONS members. Of those, 623 followed the link to the electronic survey and 64% of those (n = 401) completed the survey. METHODS: An ONS Psychosocial Project Team was convened in 2009. One of the team's goals was to develop a survey to assess members' needs. The final survey consisted of 24 items, including five items related to demographic characteristics. Response formats included Likert-type scale, yes and no, and open-ended questions. MAIN RESEARCH VARIABLES: Psychosocial care practices, education, and research. FINDINGS: Psychosocial concerns are assessed using a variety of methods. Nurse perceptions regarding primary responsibility for providing psychosocial services differ by group. Barriers to the provision of psychosocial care exist at the individual, institutional, and community levels. CONCLUSIONS: Although nurses assess patients' psychosocial needs, multiple barriers still exist related to interdisciplinary communication; knowledge of the Institute of Medicine's recommendations; and resources at the individual, institutional, and community levels. IMPLICATIONS FOR NURSING: The survey results were presented to the ONS Board of Directors, along with a three-year plan that included recommendations for future development of advocacy, practice, education, and research initiatives. Additional work is needed to effectively support RNs in their provision of psychosocial care to patients and families. PMID- 22037336 TI - Oncology update. PMID- 22037338 TI - Comparison of breast cancer risk estimations, risk perception, and screening behaviors in obese rural Korean women. AB - PURPOSE/OBJECTIVES: To assess three breast cancer risk assessment tools in obese rural Korean women. DESIGN: Cross-sectional survey design. SETTING: Community settings in the rural region of northeastern South Korea. SAMPLE: A nested cohort sample of 64 severely obese women aged 40-60 years from the Korean Genomic Regional Cohort registry. METHODS: The Breast Cancer Risk Assessment Tool of the National Cancer Institute (BCRAT-NCI), Breast Cancer Risk Appraisal for Korean Women (BCRA-K), and Estimation of Individualized Probabilities of Developing Breast Cancer for Korean Women (EIPDBC-K) were used for interview data. Mammography, women's perceptions, and screening behaviors also were analyzed. MAIN RESEARCH VARIABLES: Breast cancer risk assessment, mammography findings, women's perceptions of breast cancer risk, and breast cancer screening behaviors. FINDINGS: A total of 5 (BCRAT-NCI), 19 (BCRA-K), and 43 (EIPDBC-K) women were at higher (above average or high) risk for breast cancer. The BCRA-K (r = 0.28, p < 0.05) and EIPDBC-K (r = 0.43, p < 0.001) correlated with mammography findings. However, the BCRAT-NCI correlated only with the BCRA-K. Women's breast self examination (chi2 = 4.77, p < 0.05) and mammography findings (chi2 = 5.22, p < 0.05) differed according to their risk perception. CONCLUSIONS: Risk assessment by the BCRA-K and EIPDBC-K was related to mammography findings. Women's perception of breast cancer risk influenced their screening behaviors. When choosing a risk assessment tool, healthcare professionals should consider the ethnic and cultural backgrounds of the target population. IMPLICATIONS FOR NURSING: Healthcare professionals should use appropriate risk assessment tools in breast cancer education and counseling to help women understand their risk factors and adopt proper health behaviors. PMID- 22037339 TI - What do nurses want to learn from death education? A survey of their needs. AB - PURPOSE/OBJECTIVES: To identify what nurses want to know most about death education and to obtain baseline data to improve nurses' training and education. DESIGN: A cross-sectional survey. SETTING: Seven hospitals in Shanghai, China. SAMPLE: 617 RNs. METHODS: A cross-sectional survey using a self-report questionnaire was administered to a purposive sample of RNs. The data were analyzed with SAS(r) statistical software, version 9.1.3. MAIN RESEARCH VARIABLES: Nurses' content needs in death education and the characteristics associated with those needs. FINDINGS: Eight dimensions of needs were extracted by factor analysis from the results. The dimension of managing issues associated with death and dying had the highest score (X = 4.13), whereas issues associated with funeral planning had the lowest score (X = 3.51). The multiple linear regression analysis showed that three factors may have influenced the nurses' needs in death education: educational background, previous training about death education, and hospital size. CONCLUSIONS: Nurses had high levels of need in the content of death education, particularly regarding knowledge and skills in coping with death and dying patients (e.g., caring for patients and their families physically and psychologically). IMPLICATIONS FOR NURSING: Educators and administrators should strive to provide high-quality training for nurses and consider the roles of culture, religion, and sociodemographic characteristics when designing death education programs. PMID- 22037340 TI - Gender and ethnic differences in colorectal cancer screening embarrassment and physician gender preferences. AB - PURPOSE/OBJECTIVES: To examine colorectal cancer (CRC) screening embarrassment among men and women from three ethnic groups and the associated physician gender preference by patient gender and ethnicity. DESIGN: Cross-sectional, purposive sampling. SETTING: Urban community in Brooklyn, NY. SAMPLE: A purpose-derived, convenience sample of 245 European American, African American, and immigrant Jamaican men and women (aged 45-70 years) living in Brooklyn, NY. METHODS: Participants provided demographics and completed a comprehensive measure of CRC screening embarrassment. MAIN RESEARCH VARIABLES: Participant gender and ethnicity, physician gender, and CRC screening embarrassment regarding feces or the rectum and unwanted physical intimacy. FINDINGS: As predicted, men and women both reported reduced fecal and rectal embarrassment and intimacy concern regarding same-gender physicians. As expected, Jamaicans reported greater embarrassment regarding feces or the rectum compared to European Americans and African Americans; however, in contrast to expectations, women reported less embarrassment than men. Interactions indicated that rectal and fecal embarrassment was particularly high among Jamaican men. CONCLUSIONS: Men and women have a preference for same-gender physicians, and embarrassment regarding feces and the rectum shows the most consistent ethnic and gender variation. IMPLICATIONS FOR NURSING: Discussing embarrassment and its causes, as well as providing an opportunity to choose a same-gender physician, may be promising strategies to reduce or manage embarrassment and increase CRC screening attendance. PMID- 22037341 TI - Evaluation of a comprehensive rehabilitation program for post-treatment patients with cancer. AB - PURPOSE/OBJECTIVES: To evaluate the effects of a rehabilitation program on quality of life, fatigue, fear of movement (kinesiophobia), distress, anxiety, depression, and physical condition. DESIGN: Pretest/post-test. SETTING: An outpatient rehabilitation setting in the Oncology Centre at the University Hospital Brussels in Belgium. SAMPLE: 36 patients who had completed cancer treatment with a curative potential. METHODS: Participants completed a questionnaire and underwent a physical test at baseline and at the end of the program. The measurement instruments used included the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30, Functional Assessment of Cancer Therapy-Fatigue, Hospital Anxiety and Depression Scale, RAND-36, Tampa Scale for Kinesiophobia, Distress Barometer, and Tecumseh Step Test. MAIN RESEARCH VARIABLES: Quality of life, fatigue, kinesiophobia, distress, anxiety, depression, and physical condition. FINDINGS: Significant improvement was observed in quality of life (p < 0.001), physical condition (p = 0.007), fatigue (p = 0.01), and depression (p = 0.012). In contrast, kinesiophobia (p = 0.229), distress (p = 0.344), and anxiety (p = 0.101) did not change significantly. CONCLUSIONS: A general and significant improvement in all aspects affecting quality of life and rehabilitation was observed, but less so for aspects that might be influenced by prognostic concerns. The relative contribution of the program versus spontaneous recovery and long-term impact need to be determined further in a prospective randomized study. IMPLICATIONS FOR NURSING: Multidisciplinary rehabilitation should become part of the total care plan for patients with cancer. PMID- 22037342 TI - A symptom cluster and sentinel symptom experienced by women with lung cancer. AB - PURPOSE/OBJECTIVES: To determine the symptom experience and a sentinel symptom and to describe the relationship of participant characteristics with symptom clusters. DESIGN: Prospective, correlational study. SETTING: Clinical sites in five U.S. states. SAMPLE: 196 women six months to five years after non-small cell lung cancer diagnosis. METHODS: Symptoms were measured during the past day and past four weeks. Symptom clusters were described using a novel dummy coding approach. MAIN RESEARCH VARIABLES: Symptom occurrence and severity, demographic and clinical characteristics, health status factors, and meaning of illness. FINDINGS: About 98% of women experienced three or more symptoms in the past day. The most common symptoms reported by more than 80% of the women were fatigue, shortness of breath, anorexia, cough, and pain, with fatigue and shortness of breath rated as most severe. Sleep problems, concentration problems, and weight loss also were reported during the past four weeks. A five-symptom cluster including fatigue, shortness of breath, cough, pain, and anorexia was reported by 64% of women. Pain was identified as a sentinel symptom for that cluster. CONCLUSIONS: Most women experienced at least three symptoms in the past day, and a five-symptom cluster occurred frequently and continued post-treatment. IMPLICATIONS FOR NURSING: Women who participated in the study were, on average, two years postdiagnosis, but most experienced three or more symptoms well past treatment; therefore, vigilant ongoing clinical assessment of these women is essential. A co-occurring sentinel symptom used as a clinical indicator for the presence of a symptom cluster may be useful for clinical assessment. PMID- 22037343 TI - Improving the safety of chemotherapy administration: an oncology nurse-led failure mode and effects analysis. AB - PURPOSE/OBJECTIVES: To assess and improve the safety of hospital-based adult chemotherapy administration. DESIGN: Prospective, systems-focused clinical risk assessment. SETTING: An adult inpatient and outpatient oncology unit in a large urban hospital in the United Kingdom. SAMPLE: 8-person nurse-led multidisciplinary team, which included managerial staff and patient safety researchers. METHODS: Failure mode and effects analysis (FMEA), a prospective, systems-focused risk assessment methodology, was undertaken in biweekly team meetings and included mapping the chemotherapy administration process, identifying and numerically prioritizing potential errors (failure modes) for each process step, and generating remedial strategies to counteract them. MAIN RESEARCH VARIABLES: The analysis aimed to identify chemotherapy administration failure modes and to generate remedial strategies to address them. User feedback on the FMEA process also was collected. FINDINGS: Several specific chemotherapy failure modes were identified, the majority of which had not previously been recognized, and several novel strategies to counteract them were generated. Many of the strategies were specific, environment-focused actions, which are simple, quick, and inexpensive to implement; however, more substantive, longer-term initiatives also were generated. User feedback generally was very positive, and the process of undertaking the analysis improved multidisciplinary teamwork and communication. CONCLUSIONS: Although time and resource intensive, FMEA is a useful safety improvement tool. IMPLICATIONS FOR NURSING: Nurses should be aware of and informed about FMEA as a tool they can use in partnership with management and other disciplines to proactively and collectively improve the safety of high risk oncology procedures such as chemotherapy administration. PMID- 22037344 TI - Fatigue in young survivors of extracranial childhood cancer: a Finnish nationwide survey. AB - PURPOSE/OBJECTIVES: To evaluate self-reports of fatigue by young cancer survivors (aged 11-18 years), to compare young survivors' fatigue scores with the scores of a healthy control group and of the parent proxy evaluation, and to analyze whether demographic or disease-related factors are associated with young survivors' fatigue. DESIGN: Cross-sectional quantitative study. SETTING: An urban hospital in southwestern Finland. SAMPLE: 384 survivors diagnosed with an extracranial malignancy at age 16 or younger, who have survived four or more years postdiagnosis, and who are free of cancer. General matched population controls were randomly selected from the Finnish Population Registry. METHODS: Demographic data and a self-report written fatigue questionnaire. MAIN RESEARCH VARIABLES: Total fatigue (TF), general fatigue (GF), sleep or rest fatigue (SF), and cognitive fatigue. FINDINGS: The control populations reported significantly more issues with TF, GF, and SF than did the survivor population. In survivors, older age, the need for remedial education at school, and a sarcoma diagnosis were associated with increasing fatigue, whereas female gender, better school grades, and greater health-related quality-of-life (HRQOL) scores were associated with lower fatigue. The study variables explained 49%-65% of the variation in fatigue scores. CONCLUSIONS: Although survivors and their matched controls seem to have similar fatigue, subgroups of survivors do experience excessive fatigue, which may have an impact on their HRQOL. IMPLICATIONS FOR NURSING: This study increases the knowledge about fatigue levels of young survivors of extracranial malignancies and identifies the need for instruments specifically designed to assess fatigue in this population. The healthcare team should pay attention to the fatigue level of young survivors, particularly SF. PMID- 22037346 TI - [Pulmonary embolism and internal medicine]. PMID- 22037345 TI - Parts plus pipes: synthetic biology approaches to metabolic engineering. AB - Synthetic biologists combine modular biological "parts" to create higher-order devices. Metabolic engineers construct biological "pipes" by optimizing the microbial conversion of basic substrates to desired compounds. Many scientists work at the intersection of these two philosophies, employing synthetic devices to enhance metabolic engineering efforts. These integrated approaches promise to do more than simply improve product yields; they can expand the array of products that are tractable to produce biologically. In this review, we explore the application of synthetic biology techniques to next-generation metabolic engineering challenges, as well as the emerging engineering principles for biological design. PMID- 22037347 TI - [Gene therapy and rare diseases]. PMID- 22037348 TI - Coronary and microvascular thrombolysis with guided diagnostic ultrasound and microbubbles in acute ST segment elevation myocardial infarction. AB - BACKGROUND: During a microbubble infusion, guided high-mechanical index impulses from a diagnostic two-dimensional transducer improve microvascular recanalization in acute ST-segment elevation myocardial infarction. The purpose of this study was to further elucidate the mechanism of improved microvascular flow in normal and hyperlipidemic atherosclerotic pigs. METHODS: In 14 otherwise normal pigs, acute left anterior descending thrombotic coronary occlusions were created. Pigs subsequently received aspirin, heparin, and half-dose fibrinolytic agent (tenecteplase or tissue plasminogen activator), followed by randomization to either no additional treatment (group I) or a continuous infusion of nontargeted microbubbles and guided high-mechanical index impulses from a three-dimensional transducer (group II). Epicardial recanalization rates, ST-segment resolution, microsphere-derived myocardial blood flow, and ultimate infarct size using myocardial contrast echocardiography were compared. The same coronary thrombosis was created in a set of 12 hypercholesterolemic pigs, which were then treated with the same pharmacologic and ultrasound regimen (group III, n = 6) or the pharmacologic regimen alone (group IV, n = 6). RESULTS: Epicardial recanalization rates in groups I and II were the same (29%), but peri-infarct myocardial blood flow and ultimate infarct size improved after treatment in group II (P < .01 vs group I). In group III, epicardial recanalization was 100% (vs. 50% in group IV), and there were significant reductions in ultimate infarct size (P = .02 compared with group IV). CONCLUSIONS: Guided high-mechanical index impulses from a diagnostic transducer and nontargeted microbubbles improve peri-infarct microvascular flow in acute ST-segment elevation myocardial infarction, even when epicardial recanalization does not occur. PMID- 22037349 TI - Inverse relation of body weight and weight change with mortality and morbidity in patients with type 2 diabetes and cardiovascular co-morbidity: an analysis of the PROactive study population. AB - CONTEXT: Although weight reduction is a recommended goal in type 2 diabetes mellitus (T2DM), weight loss is linked to impaired survival in patients with some chronic cardiovascular diseases. OBJECTIVE: To assess the association of weight and weight change with mortality and non-fatal cardiovascular outcomes (hospitalisation, myocardial infarction and stroke) in T2DM patients with cardiovascular co-morbidity and the effect of pioglitazone-induced weight change on mortality. SETTING AND PARTICIPANTS: We assessed in a post hoc analysis body weight and weight change in relation to outcome in 5202 patients from the PROactive trial population who had T2DM and evidence of pre-existing cardiovascular disease. Patients were randomized to treatment with pioglitazone or placebo in addition to their concomitant glucose-lowering and cardiovascular medication. Mean follow up was 34.5 months. MAIN OUTCOME MEASURE: The impact of body weight and body weight change on all-cause mortality, cardiovascular mortality, on non-fatal cardiovascular events and on hospitalisation. RESULTS: The lowest mortality was seen in patients with BMI 30-35 kg/m(2) at baseline. In comparison to this (reference group), patients in the placebo group with BMI <22 kg/m(2) (Hazard Ratio (95% confidence intervals) 2.96 [1.27 to 6.86]; P=0.012) and BMI 22 to 25 kg/m(2) (HR 1.88 [1.11 to 3.21]; P=0.019) had a higher all-cause mortality. Weight loss was associated with increased total mortality (HR per 1% body weight: 1.13 [1.11 to 1.16]; P<0.0001), with increased cardiovascular mortality, all-cause hospitalisation and the composite of death, myocardial infarction and stroke. Weight loss of >=7.5% body weight (seen in 18.3% of patients) was the strongest cut-point to predict impaired survival (multivariable adjusted HR 4.42 [3.30 to 5.94]. Weight gain was not associated with increased mortality. Weight gain in patients treated with pioglitazone (mean+4.0+/-6.1 kg) predicted a better prognosis (HR per 1% weight gain: 0.96 [0.92 to 1.00] P=0.037) compared to patients without weight gain. CONCLUSION: Among patients with T2DM and cardiovascular co-morbidity, overweight and obese patients had a lower mortality compared to patients with normal weight. Weight loss but not weight gain was associated with increased mortality and morbidity. There may be an "obesity paradox" in patients with type 2 diabetes and cardiovascular risk. The original PROactive trial is registered as an International Standard Randomized Controlled Trial (Number ISRCTN NCT00174993). PMID- 22037350 TI - Neuronal activity and axonal sprouting differentially regulate CNTF and CNTF receptor complex in the rat supraoptic nucleus. AB - We demonstrated previously that the hypothalamic supraoptic nucleus (SON) undergoes a robust axonal sprouting response following unilateral transection of the hypothalamo-neurohypophysial tract. Concomitant with this response is an increase in ciliary neurotrophic factor (CNTF) and CNTF receptor alpha (CNTFRalpha) expression in the contralateral non-uninjured SON from which the axonal outgrowth occurs. While these findings suggest that CNTF may act as a growth factor in support of neuronal plasticity in the SON, it remained to be determined if the observed increase in neurotrophin expression was related to the sprouting response per se or more generally to the increased neurosecretory activity associated with the post-lesion response. Therefore we used immunocytochemistry and Western blot analysis to examine the expression of CNTF and the components of the CNTF receptor complex in sprouting versus osmotically stimulated SON. Western blot analysis revealed a significant increase in CNTF, CNTFRalpha, and gp130, but not LIFRbeta, protein levels in the sprouting SON at 10days post lesion in the absence of neuronal loss. In contrast, osmotic stimulation of neurosecretory activity in the absence of injury resulted in a significant decrease in CNTF protein levels with no change in CNTFRalpha, gp130, or LIFRbeta protein levels. Immunocytochemical analysis further demonstrated gp130 localization on magnocellular neurons and astrocytes while the LIFRbeta receptor was found only on astrocytes in the SON. These results are consistent with the hypothesis that increased CNTF and CNTFR complex in the sprouting, metabolically active SON are related directly to the sprouting response and not the increase in neurosecretory activity. PMID- 22037351 TI - Perturbation of 14q32 miRNAs-cMYC gene network in osteosarcoma. AB - Osteosarcoma (OS) is the common histological form of primary bone cancer and one of the leading aggressive cancers in children under age fifteen. Although several genetic predisposing conditions have been associated with OS the understanding of its molecular etiology is limited. Here, we show that microRNAs (miRNAs) at the chr.14q32 locus are significantly downregulated in osteosarcoma compared to normal bone tissues. Bioinformatic predictions identified that a subset of 14q32 miRNAs (miR-382, miR-369-3p, miR-544 and miR-134) could potentially target cMYC transcript. The physical interaction between these 14q32 miRNAs and cMYC was validated using reporter assays. Further, restoring expression of these four 14q32 miRNAs decreased cMYC levels and induced apoptosis in Saos2 cells. We also show that exogenous expression of 14q32 miRNAs in Saos2 cells significantly downregulated miR-17-92, a transcriptional target of cMYC. The pro-apoptotic effect of 14q32 miRNAs in Saos2 cells was rescued either by overexpression of cMYC cDNA without the 3'UTR or with miR-17-92 cluster. Further, array comparative genomic hybridization studies showed no DNA copy number changes at 14q32 locus in OS patient samples suggesting that downregulation of 14q32 miRNAs are not due to deletion at this locus. Together, our data support a model where the deregulation of a network involving 14q32 miRNAs, cMYC and miR-17-92 miRNAs could contribute to osteosarcoma pathogenesis. PMID- 22037352 TI - Prevalence of antibodies against seasonal influenza A and B viruses during the 2009-2010 and 2010-2011 influenza seasons in residents of Pittsburgh, PA, USA. AB - Seroprevalence of antibodies against influenza viruses from 1000 people between the ages of 0 to 90 years of age (100 samples for each decade of life) in the Pittsburgh, PA, USA was measured. One year removed from the outbreak of novel H1N1 influenza into the human population in the Northern Hemisphere and following the emergence of a new H3N2 influenza isolate, sera was collected to determine the hemagglutination-inhibition antibodies against influenza A/H1N1, A/H3N2, and B viruses representative of viruses in the vaccine used for the 2010-2011 influenza season. The seroprevalence of antibodies to influenza virus, A/California/7/2009 (H1N1), increased from the previously reported November 2009 samples and the samples collected at the end of the 2010 influenza season (June 2010) during the 2010-2011 season in all age groups, but people the under the age of 20 had the highest rise in the number of positive samples. The number of individuals positive for H1N1 stayed the same through the entire influenza season. In contrast, there were little to no positive serum samples against the H3N2 virus, A/Perth/16/2009, from samples collected during the 2009-2010 influenza season, however, titers against these viruses rose significantly during the early months of the 2010-2011 season with the highest number of positive samples detected in the very young and very old populations. However, these titers waned by May, 2011 in those over the age of 40. There was a rise in adults to the B/Brisbane/60/2008 influenza virus in adults in samples collected in October, 2010, but these titers quickly declined. The highest titers to B influenza were detected in people between the ages of 10-30 years of age. These findings may have implications for the development of vaccination strategies aiming at the protection against seasonal and/or pandemic influenza virus infection and pre-pandemic preparedness activities. PMID- 22037353 TI - Homozygous M694V as a risk factor for amyloidosis in Turkish FMF patients. AB - Secondary amyloidosis is the most severe complication of familial Mediterranean fever (FMF). Since the M694V mutation was associated with clinical severity, it was expected to be associated with amyloidosis as well. However, a number of contradicting reports have been published, especially pertinent to Turkish patients nearly 10years ago. The aim of this study was to analyze recent data regarding the association between M694V mutation and amyloidosis among FMF patients in Turkey. We conducted a comprehensive review of the literature regarding the role of M694V mutation in the development of amyloidosis secondary to FMF. Twenty-seven papers from 20 centers including 3505 Turkish subjects were reviewed. Four-hundred patients had amyloidosis and homozygous M694V was detected in 189 (47%) of the 400 amyloidotic patients which was significantly higher than that in the FMF patients not developing amyloidosis (p<0.0001). In the presented analysis we were able to reach a patient number of 400 which is much higher than all those published hitherto. Our findings confirmed that homozygous M694V is associated with amyloidosis in the Turkish population as well similar to Armenia, Israel, and Arabian countries. The necessity to treat asymptomatic or mildly symptomatic FMF patients with this genotype, even in countries where amyloidosis is rare, should be considered carefully. PMID- 22037354 TI - Efficacy of therapy for hepatocellular carcinoma with portal vein tumor thrombus: chemoembolization and stent combined with iodine-125 seed. AB - The purpose of this study is to analyze the safety and clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with portal vein stent and 125I implantation for the treatment of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma. Fifty-six patients from our department diagnosed with advanced hepatocellular carcinoma with PVTT between January 2008 and December 30, 2010 were divided into two groups. Patients in Group A were treated with TACE and portal vein stent; patients in Group B were treated with TACE, portal vein stent and 125I implantation. The success rate of TACE with portal vein stent and 125I implantation was 100%, with no severe surgery-related complications. After an 8 mo follow-up, the total clinical benefit rates were 56.7 and 88.5% for Groups A and B, respectively (p < 0.05). The median survival times (mOS) for the two groups were 5.7 and 8.9 mo, respectively (p < 0.05). The median time of progression (mTTP) of the two groups were 5.3 and 7.9 mo, respectively (p < 0.05). The 2, 6, 8, 12 and 18 mo patency rates in Group A were 100, 93.3, 83.3, 53.3 and 36.6%. Those in Group B were 100, 100, 92.3, 84.6 and 80.7%. The 2, 6 and 8 mo patency rates showed no statistical differences (p > 0.05), but the 12 and 18 mo rates did (p < 0.05). Our results suggest that TACE combined with portal vein stent and 125I implantation are both safe and effective, and 125I implantation can further postpone the restenosis of the portal vein effectively. PMID- 22037355 TI - Nitric oxide converts fatty acid alkoxyl radicals into fatty acid allyl radicals. AB - Nitric oxide (()NO) is thought to react with fatty acid alkoxyl radical, which is generated from fatty acid hydroperoxide via one-electron reduction. However, detail in the reaction remains obscure. In the present study, we examined the reaction of nitric oxide with fatty acid alkoxyl radical generated in the lipoxygenase/linoleate/13-hydroperoxyoctadecadienoate (13-HpODE) system under anaerobic conditions via HPLC equipped with mass spectrometry and photodiode array detections. In this reaction system, nitric oxide can scavenge linoleate alkoxyl radical, producing 13-ONO-9Z,11E-ODE. However, instead of 13-ONO-9Z,11E ODE, 13-NO-9E,11E-ODE and 9-NO-10E,12E-ODE were alternatively detected in the reaction solution. To explain this contradiction, we proposed a mechanism as follows: (1) 13-ONO-9E/11Z-ODE undergoes homolytic cleavage at >CHONO bond into the linoleate allyl radical and nitrogen dioxide, (2) the allyl radical undergoes resonance stabilization into the E/E-form, and (3) nitric oxide scavenges the E/E pentadiene radical at C9 or C13 position. Consequently, we concluded that nitric oxide immediately converts fatty acid alkoxyl radical into allyl radical. PMID- 22037356 TI - Allostery and the dynamic oligomerization of porphobilinogen synthase. AB - The structural basis for allosteric regulation of porphobilinogen synthase (PBGS) is modulation of a quaternary structure equilibrium between octamer and hexamer (via dimers), which is represented schematically as 8mer <=> 2mer <=> 2mer*<=> 6mer*. The "*" represents a reorientation between two domains of each subunit that occurs in the dissociated state because it is sterically forbidden in the larger multimers. Allosteric effectors of PBGS are both intrinsic and extrinsic and are phylogenetically variable. In some species this equilibrium is modulated intrinsically by magnesium which binds at a site specific to the 8mer. In other species this equilibrium is modulated intrinsically by pH with the guanidinium group of an arginine being spatially equivalent to the allosteric magnesium ion. In humans, disease associated variants all shift the equilibrium toward the 6mer* relative to wild type. The 6mer* has a surface cavity that is not present in the 8mer and is proposed as a small molecule allosteric binding site. In silico and in vitro approaches have revealed species-specific allosteric PBGS inhibitors that stabilize the 6mer*. Some of these inhibitors are drugs in clinical use leading to the hypothesis that extrinsic allosteric inhibition of human PBGS could be a mechanism for drug side effects. PMID- 22037357 TI - Surfactant protein B inhibits secretory phospholipase A2 hydrolysis of surfactant phospholipids. AB - Hydrolysis of surfactant phospholipids (PL) by secretory phospholipases A(2) (sPLA(2)) contributes to surfactant damage in inflammatory airway diseases such as acute lung injury/acute respiratory distress syndrome. We and others have reported that each sPLA(2) exhibits specificity in hydrolyzing different PLs in pulmonary surfactant and that the presence of hydrophilic surfactant protein A (SP-A) alters sPLA(2)-mediated hydrolysis. This report tests the hypothesis that hydrophobic SP-B also inhibits sPLA(2)-mediated surfactant hydrolysis. Three surfactant preparations were used containing varied amounts of SP-B and radiolabeled tracers of phosphatidylcholine (PC) or phosphatidylglycerol (PG): 1) washed ovine surfactant (OS) (pre- and postorganic extraction) compared with Survanta (protein poor), 2) Survanta supplemented with purified bovine SP-B (1 5%, wt/wt), and 3) a mixture of dipalmitoylphosphatidylcholine (DPPC), 1 palmitoyl-2-oleoyl-phosphatidylcholine (POPC), and 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG) (DPPC:POPC:POPG, 40:40:20) prepared as vesicles and monomolecular films in the presence or absence of SP-B. Hydrolysis of PG and PC by Group IB sPLA(2) (PLA2G1A) was significantly lower in the extracted OS, which contains SP-B, compared with Survanta (P = 0.005), which is SP-B poor. Hydrolysis of PG and PC in nonextracted OS, which contains all SPs, was lower than both Survanta and extracted OS. When Survanta was supplemented with 1% SP-B, PG and PC hydrolysis by PLA2G1B was significantly lower (P < 0.001) than in Survanta alone. When supplemented into pure lipid vesicles and monomolecular films composed of PG and PC mixtures, SP-B also inhibited hydrolysis by both PLA2G1B and Group IIA sPLA2 (PLA2G2A). In films, PLA2G1B hydrolyzed surfactant PL monolayers at surface pressures <=30 mN/m (P < 0.01), and SP-B lowered the surface pressure range at which hydrolysis can occur. These results suggest the hydrophobic SP, SP-B, protects alveolar surfactant PL from hydrolysis mediated by multiple sPLA(2) in both vesicles (alveolar subphase) and monomolecular films (air-liquid interface). PMID- 22037358 TI - PTEN inhibition improves wound healing in lung epithelia through changes in cellular mechanics that enhance migration. AB - The phosphoinositide-3 kinase/Akt pathway is a vital survival axis in lung epithelia. We previously reported that inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a major suppressor of this pathway, results in enhanced wound repair following injury. However, the precise cellular and biomechanical mechanisms responsible for increased wound repair during PTEN inhibition are not yet well established. Using primary human lung epithelia and a related lung epithelial cell line, we first determined whether changes in migration or proliferation account for wound closure. Strikingly, we observed that cell migration accounts for the majority of wound recovery following PTEN inhibition in conjunction with activation of the Akt and ERK signaling pathways. We then used fluorescence and atomic force microscopy to investigate how PTEN inhibition alters the cytoskeletal and mechanical properties of the epithelial cell. PTEN inhibition did not significantly alter cytoskeletal structure but did result in large spatial variations in cell stiffness and in particular a decrease in cell stiffness near the wound edge. Biomechanical changes, as well as migration rates, were mediated by both the Akt and ERK pathways. Our results indicate that PTEN inhibition rapidly alters biochemical signaling events that in turn provoke alterations in biomechanical properties that enhance cell migration. Specifically, the reduced stiffness of PTEN-inhibited cells promotes larger deformations, resulting in a more migratory phenotype. We therefore conclude that increased wound closure consequent to PTEN inhibition occurs through enhancement of cell migration that is due to specific changes in the biomechanical properties of the cell. PMID- 22037359 TI - Distribution and surfactant association of carcinoembryonic cell adhesion molecule 6 in human lung. AB - Carcinoembryonic cell adhesion molecule 6 (CEACAM6) is a glycosylated, glycophosphatidylinositol-anchored protein expressed in epithelial cells of various primate tissues. It binds gram-negative bacteria and is overexpressed in human cancers. CEACAM6 is associated with lamellar bodies of cultured type II cells of human fetal lung and protects surfactant function in vitro. In this study, we characterized CEACAM6 expression in vivo in human lung. CEACAM6 was present in lung lavage of premature infants at birth and increased progressively in intubated infants with lung disease. Of surfactant-associated CEACAM6, ~80% was the fully glycosylated, 90-kDa form that contains the glycophosphatidylinositol anchor, and the concentration (3.9% of phospholipid for adult lung) was comparable to that for surfactant proteins (SP)-A/B/C. We examined the affinity of CEACAM6 by purification of surfactant on density gradient centrifugation; concentrations of CEACAM6 and SP-B per phospholipid were unchanged, whereas levels of total protein and SP-A decreased by 60%. CEACAM6 mRNA content decreased progressively from upper trachea to peripheral fetal lung, whereas protein levels were similar in all regions of adult lung, suggesting proximal-to-distal developmental expression in lung epithelium. In adult lung, most type I cells and ~50% of type II cells were immunopositive. We conclude that CEACAM6 is expressed by alveolar and airway epithelial cells of human lung and is secreted into lung-lining fluid, where fully glycosylated protein binds to surfactant. Production appears to be upregulated during neonatal lung disease, perhaps related to roles of CEACAM6 in surfactant function, cell proliferation, and innate immune defense. PMID- 22037360 TI - Collinear facilitation and suppression at the periphery. AB - Collinear facilitation is a common phenomenon in the fovea, but it has been recently challenged at the human periphery. Since physiological studies show that facilitation is found at the periphery but only from outside the receptive field, our hypothesis was that facilitation at the periphery exists but from larger target-flanker separations than the fovea. Here, we applied a recent paradigm (Polat & Sagi, 2007) to probe facilitation at the periphery. We used a Yes/No detection task by measuring the false-positive reports (false-alarm, pfa) and hit rate (phit) for a low-contrast Gabor target (between two flankers) that appeared randomly at the fovea or at the periphery (2 degrees or 4 degrees ) to the right or left side. We used different target-flanker separations and orientations at the fovea and at the periphery. Importantly, we found that phit is affected by the target-flanker separations and orientations. Short distances show a suppression effect, but the range of suppression increases with increasing eccentricity. A facilitation effect was found for collinear configuration outside of the suppression range. A similar effect was found for the decisional criterion (Cr), which was correlated with suppression (positive) and facilitation (negative). All together, our results indicate that facilitation exists at the periphery when the target-flanker distance is properly scaled. Thus, our results indicate that collinear facilitation is a common phenomenon that exists in both the periphery and fovea. The suppression range indicates that the perceptual receptive field increases with increasing eccentricity. Our results provide a working hypothesis that explains the functional differences found between the fovea and the periphery. This supports the basic phenomena underlying visual perception, such as collinear facilitation, visual crowding, and backward masking. PMID- 22037361 TI - The effect of distractors on saccades and adaptation of saccades in strabismus. AB - This paper reports two experiments to determine the contribution of the suppressing eye to the generation of saccadic eye movements in constant strabismus. Eye movements were recorded using a Skalar infra-red recorder. Experiment 1 tested six participants with constant strabismus, pathological suppression and no clinically demonstrable binocular single vision (BSV). We explored the effect of visual distractors presented monocularly (to either the fixing eye or the strabismic eye) and binocularly, on saccade latency and accuracy. Saccade latency significantly increased when distractors were presented to the strabismic eye compared to the no distractor condition. In all participants the effect on latency, with distractors presented to the strabismic eye, was maximum when distractors were presented towards the location of the anatomical fovea. Saccade accuracy was reduced with ipsilateral distractors to the target when presented binocularly or monocularly to the fixing eye but not affected by distractors presented to the strabismic eye. Experiment 2 investigated fast disconjugate saccade adaptations in six participants with constant strabismus, pathological suppression and no clinically demonstrable BSV and for comparison 8 with normal bifoveal BSV. Saccade disconjugacy was induced using an electronic feedback system in which the calibrated eye movement position signal could be scaled by a factor (the feedback gain) to move the target visible to one eye during binocular viewing. In all BSV participants and 3 of 6 participants with constant strabismus, saccadic adaptation occurred rapidly such that under conditions of visual feedback saccades became increasingly disconjugate. These disconjugacies persisted when normal viewing conditions were restored. The presence of an adaptive mechanism to adjust the binocular co ordination of saccades in the presence of constant strabismus with suppression and no clinically demonstrable BSV has been demonstrated. Mechanisms that might explain such results are discussed. PMID- 22037362 TI - Infants' responsiveness to lightness changes on a dynamic three-dimensional surface. AB - In a looking-time study, 24 infants 6 months of age were presented with continuously folding and unfolding patterns of stripes. The luminances in the dynamic lightness constancy pattern were changed in such way that adults attribute them to changes of the various regions' orientation relative to the light source (lightness constancy display). The "reversed" lightness constancy stimulus consisted of a continuously folding and unfolding pattern, in which the luminance changes were not consistent with a striped surface illuminated from one side. The only difference between the animations was the relationship between the change in surface orientation and the change of luminances. The infants looked significantly longer at the reversed lightness constancy animation than at the lightness constancy display. This finding suggests that the infants detected the violation of the lightness constancy rules in the reversed lightness constancy stimulus. The infants were also presented with control animations to rule out the possibility that looking preferences were based on low-level properties of the display. PMID- 22037363 TI - Neural correlates of the multiple-object tracking deficit in amblyopia. AB - Deficits in multiple-object tracking have previously been reported in both the amblyopic and the clinically unaffected fellow eye of patients with amblyopia. We examined the neural correlates of this deficit using functional MRI. Attentive tracking of 1, 2 or 4 moving targets was compared to passive viewing and to baseline fixation in an amblyopic group and an age-matched control group in six regions of interest: V1, middle temporal complex (MT+), superior parietal lobule (SPL), frontal eye fields (FEF), anterior intraparietal sulcus (IPS), and posterior IPS. Activation in all regions of interest, except V1, increased with attentional load in both groups. MT+ was less active in both eyes of the amblyopic group relative to controls for passive viewing and each of the tracking conditions. Anterior IPS and FEF were less active with amblyopic eye viewing when tracking four targets. These results implicate both the low-level passive and high-level active motion systems in the multiple-object tracking deficit in amblyopia. PMID- 22037364 TI - A Magnetic change. PMID- 22037365 TI - "Injecting" fun into yearly competencies. PMID- 22037366 TI - Safe patient handling: is your facility ready for a culture change? PMID- 22037367 TI - Preventing heel pressure ulcers: economic and legal implications. PMID- 22037368 TI - Transforming nursing practice through technology and informatics. PMID- 22037370 TI - The plus of 65+. PMID- 22037371 TI - Achieving accountability... it's all about you! PMID- 22037372 TI - Interview with an informaticist. PMID- 22037373 TI - Realizing efficiencies with bar code medication administration. PMID- 22037374 TI - Focusing on core values, educational excellence. PMID- 22037375 TI - Membrane active antitumor activity of NK-18, a mammalian NK-lysin-derived cationic antimicrobial peptide. AB - As the increasing emergence of multi-drug resistant tumor cells, there is an urgent need for developing new chemotherapeutic agents. NK-lysin was a novel effector of cytotoxic T cells and natural killer (NK) cells and had broad antimicrobial activity. In this study, we developed a core region of NK-lysin termed NK-18, and studied its antitumor activity and possible action mode. Our results showed that NK-18 (with 18 amino acids) possesses potent antitumor activity against bladder and prostate cancer cells by disrupting the integrity of cell membrane, but has negligible hemolysis activity against mouse erythrocytes. In addition, CD spectra was employed to study its conformation in membrane mimicking environment. NK-18 takes a standard alpha-helical conformation in membrane mimicking environment, which could be accounted for its more potent antitumor activity compared with its low alpha-helical content homologous derivatives. These findings together with its shorter amino acid sequence and lower synthesis cost suggest that NK-18 could present an alternative therapeutic strategy to cancer chemotherapy and play a promising role in fighting the multi drug resistant tumors. PMID- 22037376 TI - Field performance of engineered male mosquitoes. AB - Dengue is the most medically important arthropod-borne viral disease, with 50-100 million cases reported annually worldwide. As no licensed vaccine or dedicated therapy exists for dengue, the most promising strategies to control the disease involve targeting the predominant mosquito vector, Aedes aegypti. However, the current methods to do this are inadequate. Various approaches involving genetically engineered mosquitoes have been proposed, including the release of transgenic sterile males. However, the ability of laboratory-reared, engineered male mosquitoes to effectively compete with wild males in terms of finding and mating with wild females, which is critical to the success of these strategies, has remained untested. We report data from the first open-field trial involving a strain of engineered mosquito. We demonstrated that genetically modified male mosquitoes, released across 10 hectares for a 4-week period, mated successfully with wild females and fertilized their eggs. These findings suggest the feasibility of this technology to control dengue by suppressing field populations of A. aegypti. PMID- 22037377 TI - Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. AB - Small-molecule protein kinase inhibitors are widely used to elucidate cellular signaling pathways and are promising therapeutic agents. Owing to evolutionary conservation of the ATP-binding site, most kinase inhibitors that target this site promiscuously inhibit multiple kinases. Interpretation of experiments that use these compounds is confounded by a lack of data on the comprehensive kinase selectivity of most inhibitors. Here we used functional assays to profile the activity of 178 commercially available kinase inhibitors against a panel of 300 recombinant protein kinases. Quantitative analysis revealed complex and often unexpected interactions between protein kinases and kinase inhibitors, with a wide spectrum of promiscuity. Many off-target interactions occur with seemingly unrelated kinases, revealing how large-scale profiling can identify multitargeted inhibitors of specific, diverse kinases. The results have implications for drug development and provide a resource for selecting compounds to elucidate kinase function and for interpreting the results of experiments involving kinase inhibitors. PMID- 22037378 TI - Comprehensive analysis of kinase inhibitor selectivity. AB - We tested the interaction of 72 kinase inhibitors with 442 kinases covering >80% of the human catalytic protein kinome. Our data show that, as a class, type II inhibitors are more selective than type I inhibitors, but that there are important exceptions to this trend. The data further illustrate that selective inhibitors have been developed against the majority of kinases targeted by the compounds tested. Analysis of the interaction patterns reveals a class of 'group selective' inhibitors broadly active against a single subfamily of kinases, but selective outside that subfamily. The data set suggests compounds to use as tools to study kinases for which no dedicated inhibitors exist. It also provides a foundation for further exploring kinase inhibitor biology and toxicity, as well as for studying the structural basis of the observed interaction patterns. Our findings will help to realize the direct enabling potential of genomics for drug development and basic research about cellular signaling. PMID- 22037379 TI - Characteristics associated with the initiation of radiation therapy after breast conserving surgery among African American and white women diagnosed with early stage breast cancer in Maryland, 2000-2006. AB - PURPOSE: Socioeconomic status appears to be an important independent barrier to breast cancer care, irrespective of insurance inequalities. Receiving radiation therapy (RT) reduces local recurrence and mortality in patients receiving breast conserving surgery (BCS). We investigated racial and socioeconomic determinants of RT initiation after BCS in Maryland. METHODS: Maryland Cancer Registry breast cancer data for the diagnosis years 2000 through 2006 were analyzed for characteristics associated with receipt of RT after BCS. We used generalized regression models to estimate RT initiation among low-income patients, adjusting for racial, demographic, and clinical covariates. RESULTS: Low-income women were more likely to be African American; older; uninsured or to use Medicare, Medicaid, or Maryland breast cancer insurance; and have tumors that were estrogen receptor and progesterone-receptor negative. Among low-income women, those at risk of not initiating RT after BCS were more likely to be African American, be older than 80 years of age, and have tumors >2 cm. CONCLUSIONS: Socioeconomic disparities were identified in the initiation of RT after BCS in Maryland from 2000 to 2006. In addition, racial disparities in RT after BCS were apparent for women diagnosed from 2000 to 2003. Additional research is needed to investigate uptake of prescribed treatments after BCS and develop strategies for reducing barriers to obtaining treatments among patients at risk for incomplete cancer care. PMID- 22037381 TI - Antidepressant use and cognitive deficits in older men: addressing confounding by indications with different methods. AB - PURPOSE: Antidepressant use has been associated with cognitive impairment in older persons. We sought to examine whether this association might reflect an indication bias. METHODS: A total of 544 community-dwelling hypertensive men aged >=65 years completed the Hopkins Verbal Learning Test at baseline and 1 year. Antidepressant medications were ascertained by the use of medical records. Potential confounding by indications was examined by adjusting for depression related diagnoses and severity of depression symptoms using multiple linear regression, a propensity score, and a structural equation model (SEM). RESULTS: Before adjusting for the indications, a one unit cumulative exposure to antidepressants was associated with -1.00 (95% confidence interval [CI], -1.94, 0.06) point lower HVLT score. After adjusting for the indications using multiple linear regression or a propensity score, the association diminished to -0.48 (95% CI, -0.62, 1.58) and -0.58 (95% CI, -0.60, 1.58), respectively. The most clinical interpretable empirical SEM with adequate fit involves both direct and indirect paths of the two indications. Depression-related diagnoses and depression symptoms significantly predict antidepressant use (p < .05). Their total standardized path coefficients on Hopkins Verbal Learning Test score were twice (0.073) or as large (0.034) as the antidepressant use (0.035). CONCLUSION: The apparent association between antidepressant use and memory deficit in older persons may be confounded by indications. SEM offers a heuristic empirical method for examining confounding by indications but not quantitatively superior bias reduction compared with conventional methods. PMID- 22037382 TI - Gene expression specificity of the mussel antifungal mytimycin (MytM). AB - We previously reported the nucleotide sequences and diversity of mytimycin (MytM) from the Mediterranean mussel, Mytilus galloprovincialis. Using real-time PCR (q PCR), we observed that the MytM gene was mainly expressed in circulating hemocytes and to a less extent in the mantle. In vivo challenge with bacteria or with the yeast, Candida albicans, did not increase the expression as measured by q-PCR in hemocytes. By contrast, injection of the filamentous fungus, Fusarium oxysporum, induced a sudden and strong increase of expression at 9h p.i. (stimulation index of 25.7 +/- 2.1). Optimum stimulating dose was 10(4) spores of F. oxysporum per mussel. In the same samples, AMP mytilin and myticin showed no stimulation. Consequently, we hypothesized the existence of 2 different signal transduction pathways, one activated by bacteria and yeast, the other triggered by filamentous fungi. A second challenge performed with F. oxysporum 24 h after the first challenge induced an increase of MytM gene expression (stimulation index of 3.5 +/- 1.7). However, this second increase was significantly lower than the first, suggesting less efficient response rather than significant protection. PMID- 22037380 TI - Risk of breast cancer in families with cleft lip and palate. AB - PURPOSE: To test whether female subjects in families with cleft lip and/or palate (CL/P) have an increased risk of breast cancer. METHODS: By using the Danish Facial Cleft Registry, we identified female subjects with CL/P, mothers of children with CL/P, and sisters to CL/P cases for the Danish birth cohorts 1911 1975. These subjects were compared with a 5% random sample of these cohorts regarding the incidence and age of onset for breast cancer registered in the Danish Hospital Discharge Register 1977-2005. RESULTS: Examining 48,404 person years for 1809 female CL/P cases (49 breast cancer cases) and 212,795 person years for 7935 female relatives (188 breast cancer cases), we found no increased breast cancer risk for either CL/P cases (hazard ratio [HR], 1.23; 95% confidence interval (CI), 0.92-1.63), mothers of children with CL/P (HR, 0.93; 95% CI, 0.80 1.08), or sisters of CL/P cases (HR, 0.94; 95% CI, 0.55-1.60), nor was there any significant differences in age of onset. CONCLUSION: Both epidemiological and genetic studies have suggested common etiological factors for breast cancer and CL/P. However, in this population-based study we were not able to confirm a general increase in the risk of breast cancer among female subjects in families with CL/P. PMID- 22037383 TI - Electron spin resonance investigation of ultra-small double walled carbon nanotubes embedded in zeolite nanochannels. AB - We report on the low temperature electron spin resonance (ESR) properties of ultra-small (0.45 nm) double walled carbon nanotubes (DWCNTs) embedded in zeolite nanochannels. An isotropic ESR signal is observed at g(c) = 2.002 77 with the spin density (S = 1/2) ~ 10(19) g(-1), which is suggested to originate from the carbon related point defects in the DWCNTs. Measurements of the ESR line width and signal intensity as a function of temperature indicate that the spins are of a localized nature as opposed to the conduction type electrons observed in large diameter CNTs. The results are consistent with the suggestion that electrons are trapped at interstitial defects. The observed linear frequency dependence of the ESR line width of embedded DWCNTs points to 'strain' as the prime source of broadening. By contrast, the study of free standing DWCNTs shows the presence of a distinctly superlinear frequency dependence of the signal width at low temperatures. The possible origin of the frequency dependence is discussed. PMID- 22037387 TI - Cardiac magnetic resonance in myocarditis. What we know and what we have to learn. PMID- 22037386 TI - Role of cardiac troponin in the diagnosis of acute myocardial infarction in comatose patients resuscitated from out-of-hospital cardiac arrest. AB - BACKGROUND: Troponin is a major diagnostic criterion of acute myocardial infarction (AMI) but in out-of-hospital cardiac arrest (OHCA) patients, its diagnostic value may be altered by cardiopulmonary resuscitation. METHODS: Single centre study assessing the diagnostic characteristics of troponin for AMI diagnosis in consecutive patients resuscitated from OHCA between 2002 and 2008 with coronary angiogram (CA) performed on admission. Patients with obvious non cardiac cause of OHCA, unsustained or absent return of spontaneous circulation were excluded. AMI was defined on CA by the presence of acute occlusion or critical stenosis with intracoronary fresh thrombus easily crossed by an angioplasty wire. Troponin concentration was recorded once on admission and once 6-12h after the OHCA. RESULTS: A total of 163 patients aged 56 (median) years (interquartile range (IQR) 48-65) was included, all comatose. Most prevalent initial OHCA rhythms were ventricular fibrillation (49%) and asystole (41%). AMI was diagnosed on coronary angiogram in 37% of the patients. Median troponin concentration on admission was 1.7 (0.3-10)ngml(-1) and sensitivity for AMI diagnosis was 72% and specificity 75% for a 2.5ngml(-1) cut-off. A combined criterion comprising ST elevation and troponin >2.5ngml(-1) had a sensitivity of 93% and specificity of 64%. Six to twelve hours after the OHCA, median troponin concentration was 7.6ngml(-1) (1.4-47.5), sensitivity was 84% and specificity 84% for a 14.5ngml(-1) cut-off. CONCLUSION: Troponin I has a good diagnostic value for AMI diagnosis in OHCA patients. In combination with ST elevation, troponin I on admission achieves a very high sensitivity. PMID- 22037388 TI - Additive value of severe diastolic dysfunction and contractile reserve in the identification of responders to cardiac resynchronization therapy. AB - AIM: The identification of responders remains challenging in cardiac resynchronization therapy (CRT). In this study we assessed the role of myocardial contractile reserve (CR) during dobutamine stress echocardiography (DSE) and resting severe diastolic dysfunction for identifying responders to CRT. METHODS AND RESULTS: Sixty-nine patients (59% with ischaemic aetiology, ejection fraction: 26 +/- 5%) referred for CRT underwent high-dose DSE. Contractile reserve was evaluated using a pressure-volume relationship, defined as systolic cuff pressure/end-systolic volume index difference between rest and peak DSE. We defined severe diastolic dysfunction as the presence of restrictive patterns and/or E/E' > 15. We divided the patients into four groups as follows: presence (CR+) or absence (CR-) of myocardial CR and presence (Diast+) or absence (Diast-) of severe diastolic dysfunction. Patients with CR+ Diast- showed higher percentage of clinical responders (91 vs. 46%, P= 0.002) and echocardiographic responders (90 vs. 25%, P= 0.001) to CRT, compared with patients with CR- Diast+. By log-rank analysis, event-free survival was significantly poorer in patients with CR- Diast+ (log rank = 18.36, P= 0.0004). CONCLUSION: Heart failure patients with severe diastolic dysfunction and absence of myocardial CR during DSE had a poorer clinical and echocardiographic response to CRT. The associated evaluations of diastolic function and CR had an additive value in the identification of responders to CRT. PMID- 22037389 TI - Link between decisions regarding resuscitation and preferences for quality over length of life with heart failure. AB - AIMS: Survival preferences, ascertained from time-trade-off utilities, have not been studied in heart failure patients who designate a 'do not resuscitate' (DNR) status. Therefore, the aim of this study was to determine the association of heart failure patients' resuscitation preferences with survival preferences and mortality in the ESCAPE trial. METHODS AND RESULTS: We analysed the association of resuscitation orders at 1 month with time-trade-off utilities and 6-month mortality. There were 26 and 349 patients with a DNR order and Full Code order, respectively. DNR patients were older, had more coronary artery disease, hypertension, renal impairment, and poorer exercise capacity than Full Code patients. DNR patients also experienced longer hospitalization and higher 6-month mortality. In multivariate analysis, DNR preference was associated with 10-fold higher odds of willingness to trade survival time (lower time-trade-off utility) in favour of improved quality of life [odds ratio 10.33, 95% confidence interval (CI) 1.65-64.80]. DNR preference was the best predictor of mortality (chi(2) 26.12, P < 0.0001, hazard ratio 6.88, 95% CI 3.28-14.41), despite adjustment for known predictors including brain natriuretic peptide. CONCLUSIONS: Heart failure patients' requests to forego resuscitation may signify more than simply 'what-if' directives for emergency care. DNR decisions may reflect preferences for intervention to enhance quality rather than prolong survival, which is particularly important as these patients have high early mortality. PMID- 22037391 TI - Characterization of a secreted macrophage migration inhibitory factor homologue of the parasitic nematode Strongyloides acting at the parasite-host cell interface. AB - Strongyloidiasis is a tropical parasitosis characterized by an alternation between free-living and parasitic stages, and by long-term infection via autoinfection. Since invasion and evasion processes of helminth parasites are substantially attained by the involvement of excretory-secretory products, we identified and characterized the 13.5 kDa macrophage migration inhibitory factor (MIF)-like protein in Strongyloides ratti. Sra-MIF is mainly secreted from the infective stage larvae (iL3), while the transcript was found at lower levels in parasitic and free-living females. Sequence analysis of the full-length cDNA showed the highest homology to the human pathogen Strongyloides stercoralis, and both are related to the MIF type-2. Unlike other mif genes, the Sra-mif includes no intron. The protein was recombinantly expressed in Escherichia coli and purified. Sra-MIF exhibited no in vitro tautomerase activity. The exposure of Sra MIF to the host immune system is confirmed by high IgG reactivities found in the hosts' sera following infection or immunization. Flow cytometric analysis indicated the binding of Sra-MIF to the monocytes/macrophage lineage but not to peripheral lymphocytes. After exposure to Sra-MIF, monocytes released IL-10 but not TNF-alpha suggesting the involvement of the secreted parasite MIF in host immune responses. PMID- 22037390 TI - Mitochondrial abnormality in sensory, but not motor, axons in paclitaxel-evoked painful peripheral neuropathy in the rat. AB - The dose-limiting side effect of the anti-neoplastic agent, paclitaxel, is a chronic distal symmetrical peripheral neuropathy that produces sensory dysfunction (hypoesthesia and neuropathic pain) but little or no distal motor dysfunction. Similar peripheral neuropathies are seen with chemotherapeutics in the vinca alkaloid, platinum-complex, and proteasome inhibitor classes. Studies in rats suggest that the cause is a mitotoxic effect on axonal mitochondria. If so, then the absence of motor dysfunction may be due to mitotoxicity that affects sensory axons but spares motor axons. To investigate this, paclitaxel exposure levels in the dorsal root, ventral root, dorsal root ganglion, peripheral nerve, and spinal cord were measured, and the ultrastructure and the respiratory function of mitochondria in dorsal roots and ventral roots were compared. Sensory and motor axons in the roots and nerve had comparably low exposure to paclitaxel and exposure in the spinal cord was negligible. However, sensory neurons in the dorsal root ganglion had a very high and remarkably persistent (up to 10 days or more after the last injection) exposure to paclitaxel. Paclitaxel evoked a significant increase in the incidence of swollen and vacuolated mitochondria in the myelinated and unmyelinated sensory axons of the dorsal root (as seen previously in the peripheral nerve) but not in the motor axons of the ventral root. Stimulated mitochondrial respiration in the dorsal root was significantly depressed in paclitaxel-treated animals examined 2-4 weeks after the last injection, whereas respiration in the ventral root was normal. We conclude that the absence of motor dysfunction in paclitaxel-evoked peripheral neuropathy may be due to the absence of a mitotoxic effect in motor neuron axons, whereas the sensory dysfunction may be due to a mitotoxic effect resulting from the primary afferent neuron's cell body being exposed to high and persistent levels of paclitaxel. PMID- 22037392 TI - Relationship of biosecuriy practices with the use of antibiotics for the treatment of infectious disease on U.S. equine operations. AB - This study is the first report estimating, on a national basis, the use of various biosecurity practices, singly and in combination, on U.S. equine operations. Use of biosecurity practices is described for operations by risk level, based on reported exposure of resident horses to outside horses during the previous 12 months. In addition, the association between use of various biosecurity practices and use of antibiotics to treat infectious disease in both adult equids and foals is reported. The comparison of these study findings with previously reported data in the literature is limited by the fact that few estimates of biosecurity practice use on equine operations have been reported and none has been published on a national basis beyond those in the National Animal Health Monitoring System (NAHMS) equine reports. A total of 78.5% of operations had some risk of exposure of resident horses to outside horses between summer 2004 and the time of the interview in summer 2005. For the majority of biosecurity practices, there was a significant (p<0.05) difference between different exposure risk levels in the percentage of operations using the practice. A higher percentage of high- and medium-risk operations implemented a combination of 4 or more biosecurity practices compared to low-risk operations. There was less use of antibiotics to treat infectious disease in adult horses on operations that required those who visit the operation to use separate equipment, change clothes/overalls, disinfect boots and equipment, or park vehicles away from animals than on those that did not. None of the other biosecurity practices were associated with use of antibiotics in adult horses and none of the biosecurity practices included in this study was associated with use of antibiotics in foals. For adults the use of antibiotics for infectious disease increased with decreasing herd size; this trend was reversed for antibiotic use in foals. The effect of exposure risk level was different for adults and foals. For adults, antibiotic use was lower for operations at higher risk; for foals, antibiotic use was higher for operations at higher risk. PMID- 22037393 TI - Diversity, biology and evolution of IncQ-family plasmids. AB - Plasmids of IncQ-family are distinguished by having a unique strand-displacement mechanism of replication that is capable of functioning in a wide variety of bacterial hosts. In addition, these plasmids are highly mobilizable and therefore very promiscuous. Common features of the replicons have been used to identify IncQ-family plasmids in DNA sequence databases and in this way several unstudied plasmids have been compared to more well-studied IncQ plasmids. We propose that IncQ plasmids can be divided into four subgroups based on a number of mutually supportive criteria. The most important of these are the amino acid sequences of their three essential replication proteins and the observation that the replicon of each subgroup has become fused to four different lineages of mobilization genes. This review of IncQ-family plasmid diversity has highlighted several events in the evolution of these plasmids and raised several questions for further research. PMID- 22037394 TI - Kinetics of phyllosemiquinone oxidation in the Photosystem I reaction centre of Acaryochloris marina. AB - Light-induced electron transfer reactions in the chlorophyll a/d-binding Photosystem I reaction centre of Acaryochloris marina were investigated in whole cells by pump-probe optical spectroscopy with a temporal resolution of ~5ns at room temperature. It is shown that phyllosemiquinone, the secondary electron transfer acceptor anion, is oxidised with bi-phasic kinetics characterised by lifetimes of 88+/-6ns and 345+/-10ns. These lifetimes, particularly the former, are significantly slower than those reported for chlorophyll a-binding Photosystem I, which typically range in the 5-30ns and 200-300ns intervals. The possible mechanism of electron transfer reactions in the chlorophyll a/d-binding Photosystem I and the slower oxidation kinetics of the secondary acceptors are discussed. PMID- 22037395 TI - Two functional sites of phosphatidylglycerol for regulation of reaction of plastoquinone Q(B) in photosystem II. AB - Functional roles of an anionic lipid phosphatidylglycerol (PG) were studied in pgsA-gene-inactivated and cdsA-gene-inactivated/phycobilisome-less mutant cells of a cyanobacterium Synechocystis sp. PCC 6803, which can grow only in PG supplemented media. 1) A few days of PG depletion suppressed oxygen evolution of mutant cells supported by p-benzoquinone (BQ). The suppression was recovered slowly in a week after PG re-addition. Measurements of fluorescence yield indicated the enhanced sensitivity of Q(B) to the inactivation by BQ. It is assumed that the loss of low-affinity PG (PG(L)) enhances the affinity for BQ that inactivates Q(B). 2) Oxygen evolution without BQ, supported by the endogenous electron acceptors, was slowly suppressed due to the direct inactivation of Q(B) during 10 days of PG depletion, and was recovered rapidly within 10h upon the PG re-addition. It is concluded that the loss of high affinity PG (PG(H)) displaces Q(B) directly. 3) Electron microscopy images of PG depleted cells showed the specific suppression of division of mutant cells, which had developed thylakoid membranes attaching phycobilisomes (PBS). 4) Although the PG-depletion for 14 days decreased the chlorophyll/PBS ratio to about 1/4, flourescence spectra/lifetimes were not modified indicating the flexible energy transfer from PBS to different numbers of PSII. Longer PG-depletion enhanced allophycocyanin fluorescence at 683nm with a long 1.2ns lifetime indicating the suppression of energy transfer from PBS to PSII. 5) Action sites of PG(H), PG(L) and other PG molecules on PSII structure are discussed. PMID- 22037396 TI - Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. AB - Mephedrone (4-methylmethcathinone) is a new and popular drug of abuse widely available on the Internet and still legal in some parts of the world. Clinical reports are now emerging suggesting that the drug displays sympathomimetic toxicity on the cardiovascular system but no studies have yet explored its cardiovascular effects. Therefore we examined the effects of mephedrone on the cardiovascular system using a combination of in vitro electrophysiology and in vivo hemodynamic and echocardiographic measurements. Patch clamp studies revealed that mephedrone, up to 30 MUM, had little effect on the major voltage-dependent ion channels of the heart or on action potentials recorded in guinea pig myocytes. Subcutaneous administration of mephedrone (3 and 15 mg/kg) to conscious telemetry-implanted rats produced dose-dependent increases in heart rate and blood pressure which persisted after pre-treatment with reserpine. Echocardiographic analysis demonstrated that intravenous injection of mephedrone (0.3 and 1mg/kg) increased cardiac function, including cardiac output, ejection fraction, and stroke volume, similar to methamphetamine (0.3mg/kg). We conclude that mephedrone is not directly pro-arrhythmic, but induces substantial increases in heart rate, blood pressure and cardiac contractility and this activity contributes to the cardiovascular toxicity in people who abuse the drug. PMID- 22037397 TI - N-vinylpyrrolidone dimer, a novel formulation excipient, causes hepatic and thyroid hypertrophy through the induction of hepatic microsomal enzymes in rats. AB - N-vinylpyrrolidone dimer (VPD) is a novel experimental formulation excipient intended for preclinical toxicology studies. In a previous 4-week toxicity study, VPD induced dose-dependent hepatocellular and thyroid gland hypertrophy in Sprague-Dawley (SD) rats. The objectives of the current investigation were to define the underlying molecular mechanisms of these changes. Two separate studies were conducted using male SD rats, daily doses of 300, 1000 or 3,000 mg/kg of VPD, and a positive control (phenobarbital at 75 mg/kg/day): (1) a 28-day study to monitor thyroid hormone levels after 7 and 28 days of dosing; (2) a 5-day study to evaluate hepatic and thyroid gland transcriptomic changes, as well as hepatic UGT activity levels. At VPD dosages of 300 mg/kg/day and higher, 2-fold increases of serum thyroid stimulating hormone (TSH) levels were observed in male SD rats after 28 days of dosing, while serum thyroxine (T4) and triiodothyronine (T3) levels were unchanged. Liver UGT enzyme activity levels were increased in VPD-treated rats after 5 days. In addition, in the 5-day study, VPD caused increased hepatic mRNA levels of a panel of drug metabolizing enzymes (DMEs) and transporters, including Cyp3a1, Cyp2b1, Ugt 2b1, and Abcc3. Similar patterns of induction were observed in primary rat hepatocytes exposed to VPD. Transcriptomic changes in the thyroid gland were identified for genes involved in thyroid hormone biosynthesis and in the FAK, PTEN, and Wnt/beta-catenin signaling pathways. Collectively, these data indicate that VPD acts as an inducer of hepatic DMEs in SD rats and that this likely leads to enhanced peripheral metabolism of T3/T4, resulting in a feedback response characterized by increased serum TSH levels, and thyroid gland hypertrophy and hyperplasia. PMID- 22037398 TI - Activation of DNA damage response pathways in human mesenchymal stem cells exposed to cisplatin or gamma-irradiation. AB - DNA damaging agents are widely used in treatment of hematogical malignancies and solid tumors. While effects on hematopoietic stem cells have been characterized, less is known about the DNA damage response in human mesenchymal stem cells (hMSCs) in the bone marrow stroma, progenitors of osteoblasts, chondrocytes and adipocytes. To elucidate the response of undifferentiated hMSCs to gamma irradiation and cisplatin, key DNA damage responses have been characterised in hMSCs from normal adult donors. Cisplatin and gamma-irradiation activated the DNA damage response in hMSCs, including induction of p53 and p21, and activation of PI3 kinase-related protein kinase (PIKK)-dependent phosphorylation of histone H2AX on serine 139, and replication protein A2 on serine4/serine8. Chemical inhibition of ATM or DNA-PK reduced DNA damage-induced phosphorylation of H2AX, indicating a role for both PIKKs in the response of hMSCs to DNA damage. Consistent with repair of DNA strand breaks, gamma-H2AX staining decreased by 24 hours following gamma-irradiation. gamma-Irradiation arrested hMSCs in the G 1 phase of the cell cycle, while cisplatin induced S-phase arrest, mediated in part by the ATR/Chk1 checkpoint pathway. In hMSCs isolated from a chronic lymphocytic leukemia (CLL) patient, p53 and p21 were induced by cisplatin and gamma irradiation, while RPA2 was phosphorylated on serine4/8 in particular following cisplatin. Compared to peripheral blood lymphocytes or the leukemia cell line K562, both normal hMSCs and CLL-derived hMSCs were more resistant to cisplatin and gamma-irradiation. These results provide insights into key pathways mediating the response of bone marrow-derived hMSCs to DNA damaging agents used in cancer treatment. PMID- 22037399 TI - Archaeosortases and exosortases are widely distributed systems linking membrane transit with posttranslational modification. AB - Multiple new prokaryotic C-terminal protein-sorting signals were found that reprise the tripartite architecture shared by LPXTG and PEP-CTERM: motif, TM helix, basic cluster. Defining hidden Markov models were constructed for all. PGF CTERM occurs in 29 archaeal species, some of which have more than 50 proteins that share the domain. PGF-CTERM proteins include the major cell surface protein in Halobacterium, a glycoprotein with a partially characterized diphytanylglyceryl phosphate linkage near its C terminus. Comparative genomics identifies a distant exosortase homolog, designated archaeosortase A (ArtA), as the likely protein-processing enzyme for PGF-CTERM. Proteomics suggests that the PGF-CTERM region is removed. Additional systems include VPXXXP CTERM/archeaosortase B in two of the same archaea and PEF-CTERM/archaeosortase C in four others. Bacterial exosortases often fall into subfamilies that partner with very different cohorts of extracellular polymeric substance biosynthesis proteins; several species have multiple systems. Variant systems include the VPDSG-CTERM/exosortase C system unique to certain members of the phylum Verrucomicrobia, VPLPA-CTERM/exosortase D in several alpha- and deltaproteobacterial species, and a dedicated (single-target) VPEID CTERM/exosortase E system in alphaproteobacteria. Exosortase-related families XrtF in the class Flavobacteria and XrtG in Gram-positive bacteria mark distinctive conserved gene neighborhoods. A picture emerges of an ancient and now well-differentiated superfamily of deeply membrane-embedded protein-processing enzymes. Their target proteins are destined to transit cellular membranes during their biosynthesis, during which most undergo additional posttranslational modifications such as glycosylation. PMID- 22037400 TI - Comprehensive transcriptome analysis of the periodontopathogenic bacterium Porphyromonas gingivalis W83. AB - High-density tiling microarray and RNA sequencing technologies were used to analyze the transcriptome of the periodontopathogenic bacterium Porphyromonas gingivalis. The compiled P. gingivalis transcriptome profiles were based on total RNA samples isolated from three different laboratory culturing conditions, and the strand-specific transcription profiles generated covered the entire genome, including both protein coding and noncoding regions. The transcription profiles revealed various operon structures, 5'- and 3'-end untranslated regions (UTRs), differential expression patterns, and many novel, not-yet-annotated transcripts within intergenic and antisense regions. Further transcriptome analysis identified the majority of the genes as being expressed within operons and most 5' and 3' ends to be protruding UTRs, of which several 3' UTRs were extended to overlap genes carried on the opposite/antisense strand. Extensive antisense RNAs were detected opposite most insertion sequence (IS) elements. Pairwise comparative analyses were also performed among transcriptome profiles of the three culture conditions, and differentially expressed genes and metabolic pathways were identified. With the growing realization that noncoding RNAs play important biological functions, the discovery of novel RNAs and the comprehensive transcriptome profiles compiled in this study may provide a foundation to further understand the gene regulation and virulence mechanisms in P. gingivalis. The transcriptome profiles can be viewed at and downloaded from the Microbial Transcriptome Database website, http://bioinformatics.forsyth.org/mtd. PMID- 22037401 TI - Translational repression of NhaR, a novel pathway for multi-tier regulation of biofilm circuitry by CsrA. AB - The RNA binding protein CsrA (RsmA) represses biofilm formation in several proteobacterial species. In Escherichia coli, it represses the production of the polysaccharide adhesin poly-beta-1,6-N-acetyl-D-glucosamine (PGA) by binding to the pgaABCD mRNA leader, inhibiting pgaA translation, and destabilizing this transcript. In addition, CsrA represses genes responsible for the synthesis of cyclic di-GMP, an activator of PGA production. Here we determined that CsrA also represses NhaR, a LysR-type transcriptional regulator which responds to elevated [Na(+)] and alkaline pH and activates the transcription of the pgaABCD operon. Gel shift studies revealed that CsrA binds at two sites in the 5' untranslated segment of nhaR, one of which overlaps the Shine-Dalgarno sequence. An epitope tagged NhaR protein, expressed from the nhaR chromosomal locus, and an nhaR posttranscriptional reporter fusion (PlacUV5-nhaR'-'lacZ) both showed robust repression by CsrA. Northern blotting revealed a complex transcription pattern for the nhaAR locus. Nevertheless, CsrA did not repress nhaR mRNA levels. Toeprinting assays showed that CsrA competes effectively with the ribosome for binding to the translation initiation region of nhaR. Together, these findings indicate that CsrA blocks nhaR translation. Epistasis studies with a pgaA-lacZ transcriptional fusion confirmed a model in which CsrA indirectly represses pgaABCD transcription via NhaR. We conclude that CsrA regulates the horizontally acquired pgaABCD operon and PGA biosynthesis at multiple levels. Furthermore, nhaR repression exemplifies an expanding role for CsrA as a global regulator of stress response systems. PMID- 22037402 TI - Characterization of type II and III restriction-modification systems from Bacillus cereus strains ATCC 10987 and ATCC 14579. AB - The genomes of two Bacillus cereus strains (ATCC 10987 and ATCC 14579) have been sequenced. Here, we report the specificities of type II/III restriction (R) and modification (M) enzymes. Found in the ATCC 10987 strain, BceSI is a restriction endonuclease (REase) with the recognition and cut site CGAAG 24-25/27-28. BceSII is an isoschizomer of AvaII (G/GWCC). BceSIII cleaves at ACGGC 12/14. The BceSIII C terminus resembles the catalytic domains of AlwI, MlyI, and Nt.BstNBI. BceSIV is composed of two subunits and cleaves on both sides of GCWGC. BceSIV activity is strongly stimulated by the addition of cofactor ATP or GTP. The large subunit (R1) of BceSIV contains conserved motifs of NTPases and DNA helicases. The R1 subunit has no endonuclease activity by itself; it strongly stimulates REase activity when in complex with the R2 subunit. BceSIV was demonstrated to hydrolyze GTP and ATP in vitro. BceSIV is similar to CglI (GCSGC), and homologs of R1 are found in 11 sequenced bacterial genomes, where they are paired with specificity subunits. In addition, homologs of the BceSIV R1-R2 fusion are found in many sequenced microbial genomes. An orphan methylase, M.BceSV, was found to modify GCNGC, GGCC, CCGG, GGNNCC, and GCGC sites. A ParB-methylase fusion protein appears to nick DNA nonspecifically. The ATCC 14579 genome encodes an active enzyme Bce14579I (GCWGC). BceSIV and Bce14579I belong to the phospholipase D (PLD) family of endonucleases that are widely distributed among Bacteria and Archaea. A survey of type II and III restriction-modification (R-M) system genes is presented from sequenced B. cereus, Bacillus anthracis, and Bacillus thuringiensis strains. PMID- 22037403 TI - Substitutions in the BamA beta-barrel domain overcome the conditional lethal phenotype of a DeltabamB DeltabamE strain of Escherichia coli. AB - BamA interacts with the BamBCDE lipoproteins, and together they constitute the essential beta-barrel assembly machine (BAM) of Escherichia coli. The simultaneous absence of BamB and BamE confers a conditional lethal phenotype and a severe beta-barrel outer membrane protein (OMP) biogenesis defect. Without BamB and BamE, wild-type BamA levels are significantly reduced, and the folding of the BamA beta-barrel, as assessed by the heat-modifiability assay, is drastically compromised. Single-amino-acid substitutions in the beta-barrel domain of BamA improve both bacterial growth and OMP biogenesis in a bamB bamE mutant and restore BamA levels close to the BamB(+) BamE(+) level. The substitutions alter BamA beta-barrel folding, and folding in the mutants becomes independent of BamB and BamE. Remarkably, BamA beta-barrel alterations also improve OMP biogenesis in cells lacking the major periplasmic chaperone, SurA, which, together with BamB, is thought to facilitate the transfer of partially folded OMPs to the soluble POTRA (polypeptide-transport-associated) domain of BamA. Unlike the bamB bamE mutant background, the absence of BamB or SurA does not affect BamA beta-barrel folding. Thus, substitutions in the outer membrane-embedded BamA beta-barrel domain overcome OMP biogenesis defects that occur at the POTRA domain of BamA in the periplasm. Based on the structure of FhaC, the altered BamA residues are predicted to lie on a highly conserved loop that folds inside the beta-barrel and in regions pointing outside the beta-barrel, suggesting that they influence BamA function by both direct and indirect mechanisms. PMID- 22037404 TI - Dimerization of the bacterial biotin carboxylase subunit is required for acetyl coenzyme A carboxylase activity in vivo. AB - Acetyl coenzyme A (acteyl-CoA) carboxylase (ACC) is the first committed enzyme of the fatty acid synthesis pathway. Escherichia coli ACC is composed of four different proteins. The first enzymatic activity of the ACC complex, biotin carboxylase (BC), catalyzes the carboxylation of the protein-bound biotin moiety of another subunit with bicarbonate in an ATP-dependent reaction. Although BC is found as a dimer in cell extracts and the carboxylase activities of the two subunits of the dimer are interdependent, mutant BC proteins deficient in dimerization are reported to retain appreciable activity in vitro (Y. Shen, C. Y. Chou, G. G. Chang, and L. Tong, Mol. Cell 22:807-818, 2006). However, in vivo BC must interact with the other proteins of the complex, and thus studies of the isolated BC may not reflect the intracellular function of the enzyme. We have tested the abilities of three BC mutant proteins deficient in dimerization to support growth and report that the two BC proteins most deficient in dimerization fail to support growth unless expressed at high levels. In contrast, the wild type protein supports growth at low expression levels. We conclude that BC must be dimeric to fulfill its physiological function. PMID- 22037405 TI - [Treatment perspectives]. AB - Celiac disease (CD) is a chronic inflammatory enteropathy caused by the ingestion of gluten. A safe and efficient but unpleasant treatment exists for CD in form of a strict gluten-free diet. Thus, there is a need for new treatment strategies, which are based on the improved and advanced understanding of the pathophysiology of CD. The first strategy consists in reducing or even eliminating major antigenic motifs in gluten, responsible for the inflammatory reaction. The use of less immunogenic wheat was suggested but this seems rather difficult to realize. However, a complete digestion of the immunogenic parts of gluten looks very promising. This can be obtained by the use of polymers, capable to sequester gluten proteins or even better via the exogenous administration of propyl endopeptidases, with two different enzymes under development. Another approach could be the use of inhibitors of tissue transglutaminase, a strategy which is under clinical investigation. Alternatively, inhibition of the site of liaison of immunostimulatory peptides with HLA molecules was suggested and is also under investigation in vivo. For patients suffering from refractory sprue, the inhibition of IL15 might be of therapeutic interest with the hope to improve the fatal outcome of many of these patients. However, the ultimate treatment approach is in form of prevention and the role of infectious agents, such as Rotavirus, in disease onset has to be considered. PMID- 22037406 TI - The effects of chronic administration of tranylcypromine and rimonabant on behaviour and protein expression in brain regions of the rat. AB - Recent findings indicate that CB1 receptor blockade might be relevant to the action of antidepressant drugs as inhibition of endocannabinoid function can increase synaptic availability of neurotransmitters; an effect also seen with chronic antidepressant drug treatment. Chronic treatments with established antidepressants also lead to raised brain BDNF levels. The aim of this study was to compare the effects of rimonabant (an inverse agonist/antagonist of CB1 receptors) with those of the antidepressant tranylcypromine (TCP), on behaviour and expression of BDNF/CREB signalling pathways in rat brain. Daily (i.p.) injections of vehicle or TCP (10 mg/kg) or rimonabant (2 mg/kg) were given for 14 days. Locomotor activity (LMA) and a conditional emotional response (CER) were measured in addition to levels of BDNF and CREB/phospho-CREB, using immunoblotting, in the frontal cortex, hippocampus, striatum and cerebellum. The velocity of movement was increased significantly on the 3rd, but not 9th, day of TCP treatment versus vehicle-treated rats (p<0.05) while rimonabant had no effect. There were no significant changes in grooming or freezing behaviours after rimonabant or TCP compared to vehicle-treated rats. Rearing was significantly reduced by TCP treatment on the 3rd, but not 9th, day of treatment (p<0.001) while rimonabant had no effect. BDNF levels were significantly increased in the frontal cortex after TCP (p<0.05) but not by rimonabant. Neither TCP nor rimonabant significantly affected CREB or p-CREB expression. In conclusion, chronic administration of TCP to rats increased BDNF expression in the frontal cortex but no similar effect was observed with rimonabant indicating that rimonabant does not show antidepressant drug-like responses after chronic treatment. PMID- 22037407 TI - Quetiapine improves response inhibition in alcohol dependent patients: a placebo controlled pilot study. AB - RATIONALE: Quetiapine has been shown to be a promising medication for the treatment of alcoholism. As an atypical antipsychotic medication with antagonist activity at D1 and D2, 5-HT(1A) and 5-HT(2A), H(1) and alpha1 and alpha2 receptors, quetiapine has been found to decrease impulsivity in other psychiatric disorders but its effects on impulsivity have not been studied in alcohol dependent patients. OBJECTIVE: This study seeks to test the effects of quetiapine on a specific dimension of impulsivity, namely response inhibition. This pilot study seeks to further elucidate the mechanisms of action of quetiapine for alcohol use disorders. METHOD: A total of 20 non-treatment seeking alcohol dependent individuals were randomized to one of the following conditions in a double-blind, placebo-controlled design: (1) quetiapine (400 mg/day); or (2) matched placebo. Participants completed two counterbalanced intravenous placebo alcohol administration sessions as well as behavioral measure of response inhibition (i.e. stop signal task) pre and post placebo-alcohol administration sessions. RESULTS: Analyses revealed a significant effect of quetiapine in improving response inhibition as measured by the stop signal task. These results provide preliminary evidence suggesting that quetiapine improves response inhibition in alcohol dependent patients, as compared to placebo. CONCLUSION: This pilot study contributes a novel putative mechanism of action of quetiapine in alcoholism, namely an improvement in response inhibition. PMID- 22037408 TI - Running wheel activity protects against increased seizure susceptibility in ethanol withdrawn male rats. AB - Ethanol withdrawal is a dysphoric condition that arises from termination of ethanol intake by dependent individuals. Common withdrawal symptoms include anxiety, increased reactivity to stimuli and increased seizure susceptibility as well as the risk of increased seizure severity. We use an animal model of dependence and withdrawal to study withdrawal behaviors and potential underlying neurobiological mechanisms. For a number of years, we have quantified pentylenetetrazol seizure thresholds as an assessment of ethanol withdrawal at both one day and three days of withdrawal. Typically, we see a significant decrease in seizure threshold (increased sensitivity to seizure induction) that persists through three days of withdrawal for male rats. Increasing evidence indicates that voluntary exercise affords protection against various challenges to physical and psychological health, including ethanol-related challenges. Therefore, the current study investigated the effect of voluntary wheel running on seizure susceptibility following chronic ethanol administration and withdrawal. We found that voluntary wheel running attenuated the increased sensitivity to pentylenetetrazol-induced seizures observed with ethanol withdrawal, at both the one-day and three-day time points. This result was especially interesting as animals with access to the running wheels consumed more of the ethanol-containing diet. These findings showed that chronic voluntary wheel running reduces the severity of ethanol withdrawal in our animal model and suggest that exercise-based interventions may have some utility in the clinical management of heavy drinking and alcohol withdrawal. PMID- 22037409 TI - Effect of ketamine on exploratory behaviour in BALB/C and C57BL/6 mice. AB - In this study, we evaluated the effect of ketamine on exploratory locomotion behaviours in the Balb/c and C57BL/6 strains of mice, which differ in their locomotion behaviours. Intraperitoneal administration of ketamine at three different doses (1, 5 or 10 mg/kg, 0.1 ml/10 gr body weight) was performed on adult male Balb/c and C57BL/6 mice. The same volume of saline was applied to the control group. The open-field and elevated plus maze apparatus were used to evaluate exploratory locomotion. In the open-field test, Balb/c mice less spend time in the centre of the field and was decreased locomotor activity compared to C57BL/6 mice (p<0.01). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in locomotor activity and an increase in the amount of time spent in the centre in the open-field test, compared to the control group (p<0.05). In C57BL/6 mice, ketamine treatment (1 and 10 mg/kg) decreased locomotor activity (p<0.05). In C57BL/6 mice, the three different doses of ketamine application each caused a decrease in the frequency of centre crossing (p<0.001) and the spent time in the centre (p<0.05). In the elevated plus maze, the number of open-arm entries, the percentage of open-arm time and total arm entries were decreased in Balb/c mice compared to C57BL/6 mice (p<0.001). Ketamine treatment of Balb/c mice at 10 mg/kg dose caused an increase in the open-arm activity (p<0.001). Ketamine application (10 mg/kg) decreased the open-arm activity in C57BL/6 mice (p<0.05). A subanaesthetic dose of ketamine increased exploratory locomotion in Balb/c mice. In contrast, a subanaesthetic dose of ketamine decreased exploratory locomotion in C57BL/6 mice. In conclusion, hereditary factors may play an important role in ketamine-induced responses. PMID- 22037410 TI - The novel adenosine A2A antagonist Lu AA47070 reverses the motor and motivational effects produced by dopamine D2 receptor blockade. AB - Dopamine D2 and adenosine A(2A) receptors interact to regulate aspects of motor and motivational function, and it has been suggested that adenosine A(2A) antagonists could be useful for the treatment of parkinsonism and depression. The present experiments were performed to characterize the effects of Lu AA47070, which is a phosphonooxymethylene prodrug of a potent and selective adenosine A(2A) receptor antagonist, for its ability to reverse the motor and motivational effects of D2 antagonism. In the first group of studies, Lu AA47070 (3.75-30 mg/kg IP) was assessed for its ability to reverse the effects of the D2 receptor antagonist pimozide (1.0 mg/kg IP) using several measures of motor impairment, including catalepsy, locomotion, and tremulous jaw movements, which is a rodent model of parkinsonian tremor. Lu AA47070 produced a significant reversal of the effects of pimozide on all three measures of parkinsonian motor impairment. In addition, Lu AA47070 was able to reverse the effects of a low dose of the D2 antagonist haloperidol on a concurrent lever pressing/chow feeding task that is used as a measure of effort-related choice behavior. The ability of Lu AA47070 to reverse the effects of D2 receptor blockade suggests that this compound could have potential utility as a treatment for parkinsonism, and for some of the motivational symptoms of depression. PMID- 22037411 TI - Behavioral deficits and cellular damage following developmental ethanol exposure in rats are attenuated by CP-101,606, an NMDAR antagonist with unique NR2B specificity. AB - NMDAR-mediated excitotoxicity has been implicated in some of the impairments following fetal ethanol exposure. Previous studies suggest that both neuronal cell death and some of the behavioral deficits can be reduced by NMDAR antagonism during withdrawal, including antagonism of a subpopulation of receptors containing NR2B subunits. To further investigate NR2B involvement, we selected a compound, CP-101,606 (CP) which binds selectively to NR2B/2B stoichiometries, for both in vitro and in vivo analyses. For the in vitro study, hippocampal explants were exposed to ethanol for 10 days and then 24 h following removal of ethanol, cellular damage was quantified via propidium iodide fluorescence. In vitro ethanol withdrawal-associated neurotoxicity was prevented by CP (10 and 25 nM). In vivo ethanol exposure was administered on PNDs 1-7 with CP administered 21 h following cessation. Activity (PNDs 20-21), motor skills (PNDs 31-33), and maze navigation (PNDs 43-44) were all susceptible to ethanol insult; treatment with CP (15 mg/kg) rescued these deficits. Our findings show that CP-101,606, a drug that blocks the NR2B/2B receptor, can reduce some of the damaging effects of "3rd trimester" alcohol exposure in our rodent model. Further work is clearly warranted on the neuroprotective potential of this drug in the developing brain. PMID- 22037412 TI - Give the gift of presence at the speed of life. PMID- 22037413 TI - The recycling endosome and its role in neurological disorders. AB - The recycling endosome (RE) is an organelle in the endocytic pathway where plasma membranes (proteins and lipids) internalized by endocytosis are processed back to the cell surface for reuse. Endocytic recycling is the primary way for the cell to maintain constituents of the plasma membrane (Griffiths et al., 1989), i.e., to maintain the abundance of receptors and transporters on cell surfaces. Membrane traffic through the RE is crucial for several key cellular processes including cytokinesis and cell migration. In polarized cells, including neurons, the RE is vital for the generation and maintenance of the polarity of the plasma membrane. Many RE dependent cargo molecules are known to be important for neuronal function and there is evidence that improper function of key proteins in RE-associated pathways may contribute to the pathogenesis of neurological disorders, including Huntington's disease. The function of the RE in neurons is poorly understood. Therefore, there is need to understand how membrane dynamics in RE-associated pathways are affected or participate in the development or progression of neurological diseases. This review summarizes advances in understanding endocytic recycling associated with the RE, challenges in elucidating molecular mechanisms underlying RE function, and evidence for RE dysfunction in neurological disorders. PMID- 22037414 TI - Caspase 8 inhibits programmed necrosis by processing CYLD. AB - Caspase 8 initiates apoptosis downstream of TNF death receptors by undergoing autocleavage and processing the executioner caspase 3 (ref. 1). However, the dominant function of caspase 8 is to transmit a pro-survival signal that suppresses programmed necrosis (or necroptosis) mediated by RIPK1 and RIPK3 (refs 2-6) during embryogenesis and haematopoiesis(7-9). Suppression of necrotic cell death by caspase 8 requires its catalytic activity but not the autocleavage essential for apoptosis(10); however, the key substrate processed by caspase 8 to block necrosis has been elusive. A key substrate must meet three criteria: it must be essential for programmed necrosis; it must be cleaved by caspase 8 in situations where caspase 8 is blocking necrosis; and mutation of the caspase 8 processing site on the substrate should convert a pro-survival response to necrotic death without the need for caspase 8 inhibition. We now identify CYLD as a substrate for caspase 8 that satisfies these criteria. Following TNF stimulation, caspase 8 cleaves CYLD to generate a survival signal. In contrast, loss of caspase 8 prevented CYLD degradation, resulting in necrotic death. A CYLD substitution mutation at Asp 215 that cannot be cleaved by caspase 8 switches cell survival to necrotic cell death in response to TNF. PMID- 22037415 TI - Raising the bar for breast health care in the United States. PMID- 22037416 TI - A burst of plant NADPH oxidases. AB - Reactive oxygen species (ROS) are highly reactive molecules able to damage cellular components but they also act as cell signalling elements. ROS are produced by many different enzymatic systems. Plant NADPH oxidases, also known as respiratory burst oxidase homologues (RBOHs), are the most thoroughly studied enzymatic ROS-generating systems and our understanding of their involvement in various plant processes has increased considerably in recent years. In this review we discuss their roles as ROS producers during cell growth, plant development and plant response to abiotic environmental constraints and biotic interactions, both pathogenic and symbiotic. This broad range of functions suggests that RBOHs may serve as important molecular 'hubs' during ROS-mediated signalling in plants. PMID- 22037417 TI - Ab initio study of magnetoelectricity in Fe/BaTiO3: the effects of n-doped perovskite interfaces. AB - On the basis of ab initio calculations we study the interfacial magnetoelectric effect in a prototypical biferroic Fe(L)/XO2/BaO/BaTiO3(001) (X = Ti, V, Co), with an Fe thickness L <= 2 monolayers. We anticipate that the use of the n-type perovskite termination instead of nominally neutral TiO2 may enhance magnetoelectricity in the system when its magnetization is robustly changed by substrate-polarization reversal. PMID- 22037418 TI - Sleep spindle-related reactivation of category-specific cortical regions after learning face-scene associations. AB - Newly acquired declarative memory traces are believed to be reactivated during NonREM sleep to promote their hippocampo-neocortical transfer for long-term storage. Yet it remains a major challenge to unravel the underlying neuronal mechanisms. Using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings in humans, we show that sleep spindles play a key role in the reactivation of memory-related neocortical representations. On separate days, participants either learned face-scene associations or performed a visuomotor control task. Spindle-coupled reactivation of brain regions representing the specific task stimuli was traced during subsequent NonREM sleep with EEG-informed fMRI. Relative to the control task, learning face-scene associations triggered a stronger combined activation of neocortical and hippocampal regions during subsequent sleep. Notably, reactivation did not only occur in temporal synchrony with spindle events but was tuned by ongoing variations in spindle amplitude. These learning-related increases in spindle-coupled neocortical activity were topographically specific because reactivation was restricted to the face- and scene-selective visual cortical areas previously activated during pre-sleep learning. Spindle-coupled hippocampal activation was stronger the better the participant had performed at prior learning. These results are in agreement with the notion that sleep spindles orchestrate the reactivation of new hippocampal-neocortical memories during sleep. PMID- 22037421 TI - The serendipitous discovery of the brain's default network. AB - One of the most unexpected findings by functional neuroimaging has been the discovery of the brain's default network - a set of brain regions that is spontaneously active during passive moments. The default network's discovery was a fortunate accident that occurred due to the inclusion of rest control conditions in early PET and functional MRI studies. At first, the network was ignored. Later, its presence was shunned as evidence of an experimental confound. Finally, it emerged as a mainstream target of focused study. Here, I describe a personal perspective of the default network's serendipitous discovery. PMID- 22037420 TI - The problem of low variance voxels in statistical parametric mapping; a new hat avoids a 'haircut'. AB - Statistical parametric mapping (SPM) locates significant clusters based on a ratio of signal to noise (a 'contrast' of the parameters divided by its standard error) meaning that very low noise regions, for example outside the brain, can attain artefactually high statistical values. Similarly, the commonly applied preprocessing step of Gaussian spatial smoothing can shift the peak statistical significance away from the peak of the contrast and towards regions of lower variance. These problems have previously been identified in positron emission tomography (PET) (Reimold et al., 2006) and voxel-based morphometry (VBM) (Acosta Cabronero et al., 2008), but can also appear in functional magnetic resonance imaging (fMRI) studies. Additionally, for source-reconstructed magneto- and electro-encephalography (M/EEG), the problems are particularly severe because sparsity-favouring priors constrain meaningfully large signal and variance to a small set of compactly supported regions within the brain. (Acosta-Cabronero et al., 2008) suggested adding noise to background voxels (the 'haircut'), effectively increasing their noise variance, but at the cost of contaminating neighbouring regions with the added noise once smoothed. Following theory and simulations, we propose to modify--directly and solely--the noise variance estimate, and investigate this solution on real imaging data from a range of modalities. PMID- 22037422 TI - Chemical constituents of Kigelia pinnata twigs and their GLUT4 translocation modulatory effect in skeletal muscle cells. AB - Phytochemical investigation of the ethanolic extract of twigs of Kigelia pinnata DC. afforded one new iridoid 7-hydroxy eucommiol (1), and nine known compounds (2 10). The structure of compounds was elucidated by extensive spectroscopic methods, including 1D, 2D NMR experiments and MS analysis. All these compounds were evaluated for GLUT4 translocation modulatory effect in skeletal muscle cells. Four of the tested compounds 1, 5, 6 and 7 showed significant stimulation of GLUT4 translocation to cell surface in skeletal muscle cells without any adverse effect on cell viability. Effect of these four compounds was concentration-dependent and comparable to standard drug rosiglitazone. These findings indicate that constituents of K. pinnata may provide leads for the therapeutics for insulin resistance and diabetes. PMID- 22037423 TI - Differential regulation of PML-RARalpha stability by the ubiquitin ligases SIAH1/SIAH2 and TRIAD1. AB - The ubiquitin proteasome system plays an important role in normal and malignant hematopoiesis and relies on the concerted action of three enzyme families. The E2 ubiquitin conjugase UBCH8 (ubiquitin conjugating enzyme [human] 8) cooperates with the E3 ubiquitin ligases SIAH1 and SIAH2 (seven in absentia homolog 1/2) to mediate the proteasomal degradation of oncoproteins. One such protein is the leukemia fusion protein PML-RARalpha (promyelocytic leukemia-retinoic acid receptoralpha) that is associated with acute promyelocytic leukemia. A limited number of UBCH8 interaction partners that participate in the UBCH8-dependent depletion of cancer-relevant proteins are known. We report here that TRIAD1 (two RING fingers and DRIL [double RING finger linked] 1), an E3 ubiquitin ligase relevant for the clonogenic growth of myloid progenitors, binds UBCH8 as well as PML-RARalpha. Moreover, there is concurrent induction of TRIAD1 and UBCH8 upon combinatorial treatment of acute promyelocytic leukemia cells with the pro apoptotic epigenetic modulator valproic acid and the differentiation inducing agent all-trans retinoic acid. However, in sharp contrast to SIAH1/SIAH2 and UBCH8, TRIAD1 binding to PML-RARalpha has no effect on its turnover. In summary, our data exclude TRIAD1 as crucial regulator of the leukemic determinant PML RARalpha, but highlight the prominence of the UBCH8/SIAH axis in PML-RARalpha degradation. PMID- 22037424 TI - Serotonin modulates hepatic 6-phosphofructo-1-kinase in an insulin synergistic manner. AB - Human and rat hepatic tissue express many serotonin (5-HT) receptor subtypes, such as 5-HT(1B), 5-HT(2A), 5-HT(2B) and 5-HT(7) receptors, which mediate diverse effects. 5-HT is known to regulate several key aspects of liver biology including hepatic blood flow, innervations and wound healing. 5-HT is also known to enhance net glucose uptake during glucose infusion in fasted dogs, but little is known about the ability of 5-HT to control hepatic glucose metabolism, especially glycolysis. This study addresses the potential of 5-HT to regulate PFK activity and the mechanisms related to the enzyme activity. Based on our results, we are the first to provide evidence that 5-HT up-regulates PFK in mouse hepatic tissue. Activation of the enzyme occurs through the 5-HT(2A) receptor and phospholipase C (PLC), resulting in PFK intracellular redistribution and favoring PFK association to the cytoskeletal f-actin-enriched fractions. Interestingly, 5-HT and insulin act in a synergistic manner, likely because of the ability of insulin to increase fructose-2,6-bisphosphate because the presence of this PFK allosteric regulator enhances the 5-HT effect on the enzyme activity. Together, these data demonstrate the ability of 5-HT to control hepatic glycolysis and present clues about the mechanisms involved in these processes, which may be important in understanding the action of 5-HT during the hepatic wound healing process. PMID- 22037425 TI - Hypersensitivity of A8344G MERRF mutated cybrid cells to staurosporine-induced cell death is mediated by calcium-dependent activation of calpains. AB - Mutations in the mitochondrial DNA can lead to the development of mitochondrial diseases such as Myoclonic Epilepsy with Ragged Red Fibers (MERRF) or Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS). We first show that human 143B-derived cybrid cells harboring either the A8344G (MERRF) or the A3243G (MELAS) mutation, are more prone to undergo apoptosis then their wild-type counterpart, when challenged with various apoptotic inducers such as staurosporine, etoposide and TRAIL. In addition, investigating the mechanisms underlying A8344G cybrid cells hypersensitivity to staurosporine-induced cell death, we found that staurosporine treatment activates caspases independently of cytochrome c release in both wild-type and mutated cells. Caspases are activated, at least partly, through the activation of calcium dependent calpain proteases, a pathway that is more strongly activated in mutated cybrid cells than in wild-type cells exposed to staurosporine. These results suggest that calcium homeostasis perturbation induced by mitochondrial dysfunction could predispose cells to apoptosis, a process that could take part into the progressive cell degeneration observed in MERRF syndrome, and more generally in mitochondrial diseases. PMID- 22037426 TI - Distinctive endoscopic ultrasound features of isolated pancreatic tuberculosis and requirements for biliary stenting. AB - BACKGROUND & AIMS: There are insufficient data about the appearance of isolated pancreatic tuberculosis on endoscopic ultrasound (EUS). The safety and efficacy of antitubercular therapy (ATT) in patients with pancreatic tuberculosis with cholestasis are also relatively unknown. METHODS: We evaluated 6 patients with isolated pancreatic head tuberculosis retrospectively and compared their EUS findings with those of 25 patients with pancreatic head adenocarcinoma. RESULTS: There was no difference in the EUS appearance between the 2 diseases. The mean diameter of the common bile duct was significantly greater in patients with pancreatic adenocarcinoma. The pancreatic duct was dilated in 20 of 25 patients with pancreatic adenocarcinoma (80%), whereas it was dilated in only 1 of 6 patients with pancreatic tuberculosis (16.6%) (P < .05). All 6 patients with pancreatic tuberculosis had a resolution of their cholestatic symptoms within 4 weeks of starting ATT alone. None of these patients required biliary stenting. CONCLUSIONS: None of the EUS features of a mass lesion caused by pancreatic tuberculosis are distinctive. Once diagnosed, these patients can be successfully treated with ATT without needing biliary stenting. PMID- 22037427 TI - Synchronous facing submucosal tumors of the duodenum in neurofibromatosis type 1. PMID- 22037428 TI - Cat scratch colon. PMID- 22037429 TI - Risk for colorectal neoplasia in patients with colonic Crohn's disease and concomitant primary sclerosing cholangitis. AB - BACKGROUND & AIMS: Patients with ulcerative colitis and concomitant primary sclerosing cholangitis (PSC) have a greater risk of developing colorectal dysplasia or invasive cancer than patients with only ulcerative colitis. Therefore, annual surveillance colonoscopies are recommended. We investigated whether primary sclerosing cholangitis is also a risk factor for colorectal dysplasia or cancer in patients with Crohn's disease of the colon. METHODS: We performed a retrospective review of data from a tertiary care hospital on 166 patients with PSC and inflammatory bowel disease; 120 had concomitant ulcerative colitis, 35 had Crohn's disease, and 11 had indeterminate colitis. The controls comprised 114 patients with colonic involvement of Crohn's disease and 102 patients with ulcerative colitis. The main outcome parameter was the development of colorectal cancer or intraepithelial neoplasia. RESULTS: Only 1 patient with colonic Crohn's disease and concomitant PSC developed dysplasia in an adenomatous polyp during a median follow-up of 10 years (range, 7-16 years). In contrast, 2 cancers and 8 cases of colorectal dysplasia were diagnosed in patients with ulcerative colitis and PSC during a median follow up of 11 years (range, 8-16 years); the crude annual incidence of dysplasia or colorectal cancer was 1 in 150 patients with ulcerative colitis. Among patients with colonic Crohn's disease without PSC, 2 developed colorectal cancer during follow-up. The presence of PSC did not increase the risk of developing colorectal dysplasia in patients with Crohn's disease (P = 1.00). CONCLUSIONS: PSC does not seem to increase the risk for dysplasia of the colon in patients with colonic Crohn's disease. PMID- 22037430 TI - Spontaneous submucosal esophageal hematoma: a cause of severe thoracic back pain. PMID- 22037431 TI - Colonic mantle cell lymphoma. PMID- 22037432 TI - Evaluation of cirrhosis with an elevated ferritin. PMID- 22037433 TI - [HBV and pregnancy]. AB - The clinical course of HBV infection in pregnant women does not usually differ from the course in non-pregnant women. Hepatitis flare rarely occurs during pregnancy, but it is frequent after delivery. HBV carrier status is associated with a higher incidence of gestational diabetes mellitus, pre-term labour and miscarriage. In the case of HBV-infected women wishing to become pregnant, the therapy could be delayed after delivery if the liver disease is mild, while if the woman has a moderate/severe liver disease, or becomes pregnant while on treatment, the potential risks of the antivirals have to be compared with the risks of hepatitis flares with progression to hepatic decompensation without treatment. The availability of highly effective passive-active immunoprophylaxis of the neonate using hepatitis B immune globulin and hepatitis B vaccine has considerably reduced the incidence of the vertical transmission of HBV infection, but a residual risk exists in cases of high maternal HBV-DNA levels: in such cases, the administration of anti-viral therapy during the third trimester of pregnancy may further reduce the risk of neonatal infection. PMID- 22037434 TI - [Loa loa filariasis in Italy: review of the literature with a clinical report]. AB - We present the case of an asymptomatic Loa loa disease in a 28-year-old Nigerian man living in Italy for 5 years. The man was admitted to our clinic for an occasional identification of hypereosinophilia (white blood cell count 5440/mmc, eosinophil 42%) and the presence of microfilaria at an hemoscopic evaluation. The diagnosis was made by testing the diurnal peripheral blood that showed a parasitaemia of 7000 microfilia/mL. The patient was treated with ivermectin 12 mg on the first day followed by albendazole 400 mg every 12 hours for 21 days with a reduction but no negativization of the parasitaemia and no collateral effect. Filariasis should be considered in all patients who come from or have stayed in endemic areas or who present alterations in the leukocyte formula, including hypereosinophilia, or some unexplainable allergic disorders. The lab diagnosis can be conducted through a hemoscopic test or directly with the identification of the adult worm, whereas the parasitaemia can be evaluated only through a hemoscopic test. The therapy can be non-conclusive or carried out with difficulty as finding diethylcarbamazine may be a hard task or potentially fatal anaphylactic reactions may occur. PMID- 22037435 TI - [Which screening for Leishmania infantum in asymptomatic blood donors?]. AB - Leishmaniasis is a protozoan infection endemic in Italy with a greatly underestimated prevalence. The recent documentation of parasitaemia in blood donors is a cause of concern for blood safety. Because there is no screening against leishmania, we performed a study to assess the presence of protozoa in blood donors of Siena district (Tuscany) during the seasonal activity of the vector. From June to October 2007, 162 patients were screened for Leishmania infantum by indirect immunofluorescence serology (IFAT) and PCR for kinetoplast (kDNA). No subject was positive for antibodies, while 11 samples (6.8%) were positive for kDNA. A second PCR (nested-PCR) was negative for all kDNA positive individuals and other subjects for a total of 55 samples (33% of total subjects). The sequence analysis of three samples positive for kDNA was compatible with mitochondrial DNA. Through the techniques used, we were unable to confirm the presence of leishmania in the blood of the subjects studied. The choice of the diagnostic protocol in blood donors remains an open issue as molecular analysis (kDNA) seems to suggest, in our experience, limits of specificity. PMID- 22037436 TI - [Aetiology of intestinal parasites in a sample of students from Mozambique]. AB - The purpose of this survey is to assess the prevalence of intestinal parasites in a population of Mozambican students. Ninety five faecal samples were collected at the three schools in Marrere, Mozambique, for a period of about one week. Observations of fresh and Giemsa-stained samples were performed at the laboratory of the Geral de Marrere Hospital; observation after concentration (FEA) was performed later at the Microbiology Laboratory of the S. Maria Nuova Hospital (Reggio Emilia, Italy). The results show a high rate of intestinal parasites among the subjects examined, supported mainly by helminths (Strongyloides stercoralis and Ancylostoma/Necator americanus), and protozoa (Dientamoeba fragilis and Giardia intestinalis). Analysis of data shows that the search for pathogenic parasites with the formalin-ethyl acetate (FEA) stool concentration technique shows higher sensitivity than the observation of fresh samples (60% vs 30%) and in some cases allows the presence of a second or third parasite to be detected. The high rate of parasitosis in endemic areas underlines the importance of lending greater attention to immigrant patients in Italy, due also to the fact that parasitosis is often found in asymptomatic forms. PMID- 22037437 TI - Socio-economic modelling of rotavirus vaccination in Castilla y Leon, Spain. AB - Rotavirus is one of the main causes of acute gastroenteritis in infants and young children. Furthermore, rotavirus is the leading cause of hospitalization and death from acute gastroenteritis among infants and young children worldwide. Although death due to rotavirus is rare in industrialized regions such as Spain, the rotavirus disease burden and its economic impact is severe. This study aims to assess systematic vaccination against rotavirus economically and socially in a Spanish region. Economic cost-effectiveness and cost-benefit assessment through a choice tree was designed. We estimated health provider costs, economic costs and quality-adjusted life years (QALYs) lost due to rotavirus infections. The study includes a fictitious cohort of 100,000 children from Castilla y Leon who were also administered the rotavirus vaccine together with diphtheria and tetanus toxoids and pertussis (DTP) . The study adopted a society and health care system perspective. A sensitivity analysis was developed to assess the uncertainty of some variables. According to the estimated incidence rate for children in Castilla y Leon, rotavirus immunization is projected to prevent 45% of cases with RotaTeq and 57% with Rotarix. The respective cost per QALY is about Euro 75,000 and 50,000 from the perspective of the health care system. Routine infant vaccination in Castilla y Leon using either rotavirus vaccine is not profitable from the payer's perspective and is not cost-effective under basic case assumptions unless the vaccine is available at a lower cost. PMID- 22037439 TI - Pneumocystis jiroveci pneumonia (PCP) misdiagnosed as pandemic influenza H1N1 in a renal transplant patient. AB - Respiratory infections are of particular concern in transplant patients. However, there is a significant overlap in the symptoms caused by different pathogens. Here, we report a case of Pneumocystis jiroveci pneumonia (PCP) in a renal transplant patient which was initially misdiagnosed as pandemic influenza H1N1. The patient did not improve under oseltamivir treatment and bronchoscopy was performed five days later after hospitalization. PCP was diagnosed by microscoping evaluation of bronchoalveolar lavage (BAL) fluid. Besides, BAL and serum of the patient yielded a large amount of 1,3-beta-D-glucan, a cellwall compotent of medically important mycoses including P. jiroveci. The patient was successfully treated with intravenous trimethoprim-sulfamethoxazole. Due to the lack of sensitivity of influenza case definitions, the attending physicians should be careful about alternative diagnoses particularly in transplant patients with severe respiratory infections. PMID- 22037438 TI - [HPV-related diseases and screening program in male partners]. AB - HPV is a sexually transmitted virus. The main risk factor for infection of the female population is the heterosexual transmission with partners who are infected with human papilloma virus (HPV). HPV infection is very common in sexually active males, and it is the most common STDs. In our experience the prevalence of infection is just under 50%. There are careful and well-established procedures that are applied to women with HPV; on the contrary, with regard to male population, there is, often, less focus and less sensitivity during both diagnostic and therapeutic strategies. The objectives of this study respond to two specific questions: 1. Is it useful to control male partner? 2. What tests are advisable and necessary for a proper definition of the problem? In this study 160 male patients, partners of patients with HPV infection, were examined by peniscopia, the search for HPV-DNA and biopsy of the penis. The study results show that the percentage of HPV infection of the male partners of women with HPV infection is quite high, ranging from 47 to 49% in relation to the methods used. The prevalence of patients with high-risk virus which stands at over 60%. Moreover, from 17.5% to 40.5%, we observed an infection with multiple genotypes of which is known as a hazard factor of aggravation and persistence of HPV infection. In conclusion, HPV-related diseases is a clinical infection of the couple and it is obvious that to the couple should be given great attention. For an important and effective prevention of transmission of HPV from the male subject to viruses to woman, and for the prevention ping-pong effect, it is essential to submit all the male partners of women infected with HPV peniscopia, HPV tests, and possibly a biopsy of the penis. PMID- 22037440 TI - Unsuspected giant hydatid cyst of the liver in an 87-year-old woman. AB - Hydatid cystic disease from Echinococcus granulosus is described in some Brazilian as well as Italian areas. Liver hydatidosis is the most common presentation, which may evolve without symptoms. The authors describe an 87-year old woman with an unsuspected giant hydatid cyst of the liver and emphasize the diagnostic challenges, mainly involving patients from non-endemic regions. PMID- 22037441 TI - [Streptococcus gordonii extensive multiple subcutanoeus abscesses]. AB - We describe extensive multiple subcutaneous abscesses involving the peri-scapular region, the right posterior and lateral peri-trochanteric area and ipsilateral thigh occurring in a 66-years-old woman. Streptococcus gordonii was identified as the unique pathogen. Despite this microrganism is generally considered not pathogenic, it has been previously described as responsible for two cases of peritonitis and one case of endocarditis. The patient has been treated with immediate surgical incision and drainage and was cured after two months of antibiotic therapy, medications and hyperbaric oxygen therapy. PMID- 22037442 TI - Epidemic waves of the Black Death in the Byzantine Empire (1347-1453 AD). AB - The lack of valid demographic data and the literary ambiguities of the Byzantine chroniclers raise questions about the actual size and mortality rate of the Black Death in the Byzantine Empire. This study presents for the first time a quantitative overview of the Black Death in Byzantium for the period 1347-1453. Our data were obtained from descriptions of the plague, by prominent Byzantine historians and scholars, grouped by time of appearance and geographical spread. During the period 1347-1453, a total of 61 plague reports were noted, which can be distinguished in nine major epidemic waves, 11 local outbreaks and 16 disease free periods. The capital Constantinople and the Venetian colonies of the Ionian and Aegean Sea were the areas most affected by the plague. The epidemic waves of the Black Death in Byzantium had a total average duration of 3.2 years. Scientific ignorance of the nature of the disease, a turbulent period of warfare and an organized maritime network seem to have contributed to the spread of the disease. Employing quantitative analysis, our multidisciplinary study sheds light from various standpoints on the evolution and dynamic of the plague in the South eastern Mediterranean during the 14th and 15th centuries, despite the lack of sound morbidity and mortality data. PMID- 22037443 TI - Oxidized phospholipid based pH sensitive micelles for delivery of anthracyclines to resistant leukemia cells in vitro. AB - A self-assembled micelle drug delivery system was constructed with an oxidized phospholipid for anthracycline anti-cancer drug delivery. An oxidized phospholipid, 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazPC), was chosen to fabricate micelles via both electrostatic and hydrophobic interactions for delivery of doxorubicin (DOX) and idarubicin (IDA). The formation of ion-pair complexes between PazPC and DOX was first investigated under different pH conditions. Drug-loaded PazPC micelles at a 5:1 molar ratio of lipid/drug at pH 7.0 were then prepared by the solvent evaporation method. The empty and drug loaded PazPC micelles exhibited a small particle size (~10 nm) and high encapsulation efficiency. In vitro stability and release profile indicated that the micelles were stable at physiological conditions, but exhibited pH-sensitive behavior with accelerated release of DOX or IDA in an acidic endosome environment. Finally, in vitro uptake and cytotoxicity were evaluated for leukemia P388 and its resistant subline P388/ADR. The drug-loaded PazPC micelles enhanced drug uptake and exhibited higher cytotoxicity in both leukemia cells in comparison to free drugs. In conclusion, we developed a novel pH sensitive oxidized phospholipid-based micellar formulation which could potentially be useful in delivering anthracycline anti-cancer drugs and provide a novel strategy for increasing the therapeutic index while overcoming multidrug resistance for leukemia treatment. PMID- 22037444 TI - Effect of fatty acids on the transdermal delivery of donepezil: in vitro and in vivo evaluation. AB - The effect of fatty acids on the skin permeation of donepezil base (DPB) and its hydrochloride salt (DPH) were studied in vitro using hairless mouse and human cadaver skin. DPB and DPH were solubilized in propylene glycol (PG) containing 1% (w/v) fatty acid, after which the in vitro permeation through hairless mouse skin and human cadaver skin were evaluated using Keshary-Chien diffusion cells. The optimized formulation obtained from the in vitro study was then tested in rats for an in vivo pharmacokinetic study. The relative in vitro skin permeation rate of donepezil (DP) through the hairless mouse skin showed a parabolic relationship with increased carbon length of the fatty acid enhancers. Among the fatty acids tested, oleic acid for DPB and palmitoleic acid for DPH showed the highest enhancing effect, respectively. Both the permeation rates of DPB and DPH evaluated in human cadaver skin were in good correlation with those in hairless mouse skin, regardless of the presence of fatty acids. This suggests that the mouse skin model serves as a useful in vitro system that satisfactorily represents the characteristics of the human skin. Moreover, based on the in vitro results, the optimal formulation that could maintain the human plasma concentration of 50 ng/mL was determined to be 10mg DP with 1% (w/v) enhancer. When the DP transdermal formulations were applied to the abdominal skin of rats (2.14 cm(2)), the C(ss) was maintained for 48 h, among which the highest value of 52.21 +/- 2.09 ng/mL was achieved with the DPB formulation using oleic acid. These results showed that fatty acids could enhance the transdermal delivery of DP and suggested the feasibility of developing a novel transdermal delivery system for clinical use. PMID- 22037419 TI - Detecting global and local hippocampal shape changes in Alzheimer's disease using statistical shape models. AB - The hippocampus is affected at an early stage in the development of Alzheimer's disease (AD). With the use of structural magnetic resonance (MR) imaging, we can investigate the effect of AD on the morphology of the hippocampus. The hippocampal shape variations among a population can be usually described using statistical shape models (SSMs). Conventional SSMs model the modes of variations among the population via principal component analysis (PCA). Although these modes are representative of variations within the training data, they are not necessarily discriminative on labeled data or relevant to the differences between the subpopulations. We use the shape descriptors from SSM as features to classify AD from normal control (NC) cases. In this study, a Hotelling's T2 test is performed to select a subset of landmarks which are used in PCA. The resulting variation modes are used as predictors of AD from NC. The discrimination ability of these predictors is evaluated in terms of their classification performances with bagged support vector machines (SVMs). Restricting the model to landmarks with better separation between AD and NC increases the discrimination power of SSM. The predictors extracted on the subregions also showed stronger correlation with the memory-related measurements such as Logical Memory, Auditory Verbal Learning Test (AVLT) and the memory subscores of Alzheimer Disease Assessment Scale (ADAS). PMID- 22037445 TI - Optimized dextran-polyethylenimine conjugates are efficient non-viral vectors with reduced cytotoxicity when used in serum containing environments. AB - Polyethylenimine (PEI) is a cationic polymer that is an efficient transfection reagent marred by high toxicity and a susceptibility to aggregate in the presence of serum. Dextran is a biodegradable natural polysaccharide that can be used to reduce the toxicity of PEI and increase its stability in the presence of serum. In this study, small branched PEI units (800/2000 Da) were attached to dextran (Dex; 15/100-200 kDa) to form dextran-polyethylenimine (Dex-PEI) conjugates. The Dex-PEI conjugates were then tested as a gene carrier in the model HEK293 cell line. Dex-PEI conjugates displayed significantly lower cytotoxicity than PEI (25k). Both Dex-PEI and PEI efficiently delivered firefly luciferase encoded plasmid DNA (pDNA) to the HEK293 cells. Dex-PEI resulted in moderately lower transfection efficiencies than PEI 25k when the transfection was carried out in media without serum for 4h. However, in the presence of serum, which more accurately predicts the anticipated environment of non-viral vectors in vivo, Dex PEI and unmodified PEI generated similar transfection efficiencies when incubated with the cells for 4h. When the incubation time of the vectors was increased to 48h, significantly higher transfection efficiencies were generated by Dex-PEI in comparison to PEI. Turbidity measurements showed that complexes formed between plasmid DNA and unmodified PEI were more susceptible to aggregation in serum containing media than complexes formed from pDNA and Dex-PEI. Dex-PEI conjugates are therefore believed to have greater potential for translational applications because of lower cytotoxicity characteristics and improved stability in serum containing environments. PMID- 22037446 TI - Optimization of rapamycin-loaded acetalated dextran microparticles for immunosuppression. AB - Immunosuppressive drugs can treat autoimmune disorders and limit rejection with organ transplants. However, delivering immunosuppressants like rapamycin systemically can have harmful side-effects. We aim to potentially reduce these toxic side-effects by encapsulating rapamycin in a polymeric microparticle to passively target phagocytes, the cells integral in immunosuppression. Acetalated dextran (Ac-DEX) is a recently described, biocompatible polymer which undergoes tunable burst degradation at the acidic conditions present in the phagosome (pH 5) but slower degradation at extracellular conditions (pH 7.4), thereby making it an ideal candidate for immune applications. Rapamycin-loaded microparticles were fabricated from Ac-DEX through a single emulsion (water/oil) technique. Optimized microparticles were determined by varying the chemical and physical parameters during particle synthesis. Microparticles synthesized from Ac-DEX with a molecular weight of 71 k had higher encapsulation efficiency of rapamycin and slower overall degradation than microparticles synthesized from 10k Ac-DEX. To evaluate the ability of rapamycin-loaded Ac-DEX microparticles to reduce a pro inflammatory response, they were incubated with lipopolysaccharide-stimulated RAW macrophages. RAW macrophages treated with rapamycin-loaded microparticles exhibited reduced nitric oxide production and favorable cell viability. Overall, we have shown optimization of immunosuppressive rapamycin-loaded microparticles using the novel polymer Ac-DEX. These particles will be advantageous for future applications in immune suppression therapies. PMID- 22037448 TI - Histamine increases the level of IFNgamma produced by HIV-1 specific CTLs and this production depends on total IgE level. AB - BACKGROUND: The HIV (human immunodeficiency virus) population remains a global concern whose treatment is effective, though not yet optimal. Immune based therapies have thus far been disappointing and still need to be explored further. Based on published data suggesting that the functions of cytotoxic CD8+ T lymphocytes (CTL) can be improved by histamine, we investigated the effect of histamine in vitro on HIV-1 specific CD8+ T lymphocytes in HIV+ subjects. RESULTS: 60 HIV+ subjects were included in the study. We evaluated CTL function by IFNgamma (interferon gamma) production (using the enzyme-linked immunospot assay (Elispot), BD Bioscience). Changes in the production of IFNgamma after incubation with histamine were compared with the levels of total IgE (immunoglobulin E, measured using a Dade Behring analyzer), because histamine is endogenously released through IgE. Activation of HIV-specific CTL by histamine occurs via H2R (histamine receptors). Thus we attempted to block this activation using cimetidine (antagonist H2R). CONCLUSIONS: We found an increase in IFNgamma production after the activation of HIV-1 specific CD8+ T lymphocytes by histamine (this elevation was blocked by cimetidine), furthermore, we demonstrated a negative correlation between the production of IFNgamma and levels of total IgE. PMID- 22037447 TI - Tannate complexes of antihistaminic drug: sustained release and taste masking approaches. AB - The aim of this investigation was to evaluate the complexation potential of brompheniramine maleate (BPM) and tannic acid (TA) for sustained release and taste masking effects. The complexes (1:1-1:7 TA to BPM ratio) were prepared by the solvent evaporation method using methanol, phosphate buffer pH 6.8 or 0.1N HCl as common solvents. The complexes were characterized microscopically by scanning electron microscopy (SEM), chemically by Fourier transform infrared (FTIR) and solid-state NMR (SSNMR), thermally by differential scanning calorimetry (DSC), for crystallinity by powder X-ray powder diffraction (PXRD), for organoleptic evaluation by electronic tongue (e-tongue), and for solubility in 0.1N HCl and phosphate buffer pH 6.8. The dissolution studies were carried out using the USP II method at 50 rpm in 500 ml of dissolution media (0.1N HCl or phosphate buffer pH 6.8). SEM images revealed that the morphology of complexes were completely different from the individual components, and all complexes had the same morphological characteristics, irrespective of the solvent used for their preparation, pH or ratio of BPM and TA. The FTIR spectra showed the presence of chemical interactions between the TA and BPM. DSC, PXRD and SSNMR indicated that the drug lost its crystalline nature by formation of the complex. Complexation has significantly reduced the solubility of BPM and sustained the drug release up to 24h in phosphate buffer pH 6.8 media. The bitter taste of the BPM was completely masked which was indicated by Euclidean distance values which was far from the drug but near to its placebo in the complexes in all ratios studied. The taste masked complexes can be potentially developed as suitable dosage forms for pediatric use. In summary, complexation of BPM and TA effectively sustained the dissolution and masked the bitter taste of drug for the development of suitable dosage forms for pediatric use. PMID- 22037449 TI - Drug withdrawal-induced depression: serotonergic and plasticity changes in animal models. AB - This review discusses recent research of mood disorders associated with the cessation of psychoactive substances, with an emphasis on preclinical studies that have been published in the last decade. Animal models exhibiting anhedonic and depressive-like behaviours associated with drug withdrawal have been used to study the neurobiology of mood disorders and have culminated in the identification of novel targets for the treatment of depressive-like symptoms. This review will introduce the behavioural as well as the neurochemical and plasticity changes in depressed patients and several animal models of depression. Following, we provide a more in-depth discussion of the role of serotonergic neurotransmission and Hypothalamic-Pituitary-Adrenal (HPA) axis regulation as well as the neurogenic changes occurring after chronic drug intake focusing on the withdrawal associated depression. Although we mainly focus on animal data, some relevant human studies are also discussed. Establishing the commonalities of depression and drug-seeking behaviour will allow us to elucidate the factors driving the high co-morbidity between mood disorders and drug dependence. PMID- 22037450 TI - Molecular mechanisms of temperature-dependent sex determination in the context of ecological developmental biology. AB - Temperature-dependent sex determination (TSD) is a prime example of phenotypic plasticity in that gonadal sex is determined by the temperature of the incubating egg. In the red-eared slider turtle (Trachemys scripta), the effect of temperature can be overridden by exogenous ligands, i.e., sex steroid hormones and steroid metabolism enzyme inhibitors, during the temperature-sensitive period (TSP) of development. Precisely how the physical signal of temperature is transduced into a biological signal that ultimately results in sex determination remains unknown. In this review, we discuss the sex determining pathway underlying TSD by focusing on two candidate sex determining genes, Forkhead box protein L2 (FoxL2) and Doublesex mab3- related transcription factor 1 (Dmrt1). They appear to be involved in transducing the environmental temperature signal into a biological signal that subsequently determines gonadal sex. FoxL2 and Dmrt1 exhibit gonad-typical patterns of expression in response to temperature during the TSP in the red-eared slider turtle. Further, the biologically active ligands regulate the expression of FoxL2 and Dmrt1 during development to modify gonad trajectory. The precise regulatory mechanisms of expression of these genes by temperature or exogenous ligands are not clear. However, the environment often influences developmental gene expression by altering the epigenetic status in regulatory regions. Here, we will discuss if the regulation of FoxL2 and Dmrt1 expression by environment is mediated through epigenetic mechanisms during development in species with TSD. PMID- 22037451 TI - Re: Mannion CJ, Kanatas A, Telfer MR. One dog bite too far [Br. J. Oral Maxillofac. Surg. 49 (2011) 159, doi:10.1016/j.bjoms.2010.12.008]. PMID- 22037452 TI - 17beta-Estradiol attenuates saturated fatty acid diet-induced liver injury in ovariectomized mice by up-regulating hepatic senescence marker protein-30. AB - Senescence marker protein-30 (SMP30) plays an important role in intracellular Ca(2+) homeostasis. The aim of the present study was to investigate the effects of estrogens on liver apoptotic damage and changes in SMP30 expression induced by a high saturated fatty acid diet (HSFD). Ovariectomized mice (OVX) and sham operated mice (SHAM) were randomly divided into five groups: SHAM fed a normal diet (SHAM/ND), SHAM fed HSFD (SHAM/HSFD), OVX fed ND (OVX/ND), OVX fed HSFD (OVX/HSFD) and OVX fed HSFD with 17beta-estradiol (E2) supplementation using an implanted slow-release pellet (OVX/HSFD+E2). After 8 weeks, markers of endoplasmic reticulum (ER) stress and apoptosis, and levels of tumor necrosis factor-alpha (TNFalpha and SMP30 expression were investigated. Compared with SHAM/ND, OVX/HSFD mice showed significantly increased spliced X-box protein-1 (s XBP1), phosphorylated eukaryotic initiation factor-2alpha (p-eIF2alpha), glucose regulated protein 78 (GPR78), C/EBP homologous protein (CHOP), cytosolic cytochrome c, caspase-3 activity, and TNFalpha, and significantly decreased SMP30. These differences in OVX/HSFD mice were restored to the levels of SHAM/ND mice by E2 supplementation. These results suggest that E2 supplementation attenuates HSFD-induced liver apoptotic death in ovariectomized mice by up regulating SMP30. PMID- 22037453 TI - Genetic induction of phosphate toxicity significantly reduces the survival of hypercholesterolemic obese mice. AB - OBJECTIVE: The adverse effects of metabolic disorders in obesity have been extensively studied; however, the pathologic effects of hyperphosphatemia or phosphate toxicity in obesity have not been studied in similar depth and detail, chiefly because such an association is thought to be uncommon. Studies have established that the incidence of obesity-associated nephropathy is increasing. Because hyperphosphatemia is a major consequence of renal impairment, this study determines the in vivo effects of hyperphosphatemia in obesity. METHODS AND RESULTS: We genetically induced hyperphosphatemia in leptin-deficient obese (ob/ob) mice by generating ob/ob and klotho double knockout [ob/ob-klotho(-/-)] mice. As a control, we made ob/ob mice with hypophosphatemia by generating ob/ob and 1-alpha hydroxylase double knockout [ob/ob-1alpha(OH)ase(-/-)] mice. Compared to the wild-type mice, all three obese background mice, namely ob/ob, ob/ob klotho(-/-), and ob/ob-1alpha(OH)ase(-/-) mice developed hypercholesterolemia. In addition, the hyperphosphatemic, ob/ob-klotho(-/-) genetic background induced generalized tissue atrophy and widespread soft-tissue and vascular calcifications, which led to a shorter lifespan; no such changes were observed in the hypophosphatemic, ob/ob-1alpha(OH)ase(-/-) mice. Significantly, in contrast to the reduced survival of the ob/ob-klotho(-/-) mice, lowering serum phosphate levels in ob/ob-1alpha(OH)ase(-/-) mice showed no such compromised survival, despite both mice being hypercholesterolemic. CONCLUSION: These genetic manipulation studies suggest phosphate toxicity is an important risk factor in obesity that can adversely affect survival. PMID- 22037455 TI - Live-cell real-time imaging reveals role of mitochondria in cell-to-cell transmission of HIV-1. AB - We used live-cell, real-time fluorescence imaging of co-cultures of HIV-1 infected T cells and uninfected target cells to examine the action of mitochondria during cell-to-cell transmission of the virus. We find that mitochondria of HIV infected cells enter uninfected target cells and advance viral spread. We show that human mitochondria serve as viral reservoirs and carriers and that they can move between cells. This was confirmed by our results that purified mitochondria from HIV infected cells are infectious, and that mitochondrial inhibitors block HIV transmission. Viral infection and replication in the target cells were verified by syncytial formation and HIV-1 core protein p24 production. Our results offer new insights into the cellular mechanisms of viral transmission and identify mitochondria as new host targets for viral infection. PMID- 22037454 TI - Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium. AB - Dysferlin is a membrane-anchored protein known to facilitate membrane repair in skeletal muscles following mechanical injury. Mutations of dysferlin gene impair sarcolemma integrity, a hallmark of certain forms of muscular dystrophy in patients. Dysferlin contains seven calcium-dependent C2 binding domains, which are required to promote fusion of intracellular membrane vesicles. Emerging evidence reveal the unexpected expression of dysferlin in non-muscle, non mechanically active tissues, such as endothelial cells, which cast doubts over the belief that ferlin proteins act exclusively as membrane repair proteins. We and others have shown that deficient trafficking of membrane bound proteins in dysferlin-deficient cells, suggesting that dysferlin might mediate trafficking of client proteins. Herein, we describe the intracellular trafficking and movement of GFP-dysferlin positive vesicles in unfixed reconstituted cells using live microscopy. By performing GST pull-down assays followed by mass spectrometry, we identified dysferlin binding protein complexes in human vascular endothelial cells. Together, our data further support the claims that dysferlin not only mediates membrane repair but also trafficking of client proteins, ultimately, help bridging dysferlinopathies to aberrant membrane signaling. PMID- 22037456 TI - TGF-beta-stimulated aberrant expression of class III beta-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells. AB - The class III beta-tubulin isotype (beta(III)) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III beta-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-beta (TGF-beta) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-beta on the aberrant expression of class III beta-tubulin and the intracellular signaling pathway mediating these changes. TGF-beta-induced aberrant expression and O-linked-beta-N-acetylglucosamine (O-GlcNac) modification of class III beta-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-beta also stimulated phosphorylation of ERK. TGF-beta-induced aberrant expression of class III beta tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-beta stimulated aberrant expression of class III beta-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-beta stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases. PMID- 22037457 TI - Protein tyrosine phosphatase CD45 as a molecular biosensor of hydrogen peroxide generation in cell culture media. AB - We have designed a useful method of assessing reactive oxygen species generation in biological fluids. The novel assay utilizes tyrosine phosphatase CD45 as a biosensor of oxidative stress. Applying this new method, we examined oxygen species generation in the following cell culture media: RPMI 1640, DMEM, DMEM enriched with pyruvate and MEM. We discovered that the media (especially RPMI 1640) significantly reduced the activity of protein tyrosine phosphatase. The media-caused inactivation of CD45 was reversible after treatment with dithiothreitol being a powerful reducing agent. Interestingly, the media supplemented with catalase did not exhibit any inhibitory effect on CD45 activity which suggests a hydrogen peroxide-mediated mechanism of the enzyme inactivation. In addition to that, we assessed the impact of oxidative stress level on the activity of CD45 as measured in Jurkat cells cultured in RPMI 1640 either exposed or not exposed to the light of laminar flow cabinet fluorescent lamp. We found that Jurkat cells that were exposed to light displayed ca. 20% lower activity of CD45 than the cells protected against the light. The obtained results indicate that production of hydrogen peroxide in the medium leading to inhibition of CD45 was light-dependent, and that careful protection of cell culture media from the light may help to prevent the artifact in cell studies. Hydrogen peroxide, responsible for CD45 inactivation, can be generated in cell culture media after exposition to light due to photoreactive amino acids present in the media. PMID- 22037458 TI - Binding of abscisic acid to human LANCL2. AB - The phytohormone abscisic acid (ABA) is the central regulator of abiotic stress in plants and plays important roles during plant growth and development. In animal cells, ABA was shown to be an endogenous hormone, acting as a stress signal and stimulating cell functions involved in inflammatory responses and in insulin release. Recently, we demonstrated that Lanthionine synthetase component C-like protein 2 (LANCL2) is required for ABA binding to the plasmamembrane of granulocytes and for the activation of the signaling pathway triggered by ABA in human granulocytes and in rat insulinoma cells. In order to investigate whether ABA activates LANCL2 via direct interaction, we performed specific binding studies on human LANCL2 recombinant protein using different experimental approaches (saturation binding, scintillation proximity assays, dot blot experiments and affinity chromatography). Altogether, results indicate that human recombinant LANCL2 binds ABA directly and provide the first demonstration of ABA binding to a mammalian ABA receptor. PMID- 22037459 TI - The presence of centrioles and centrosomes in ovarian mature cystic teratoma cells suggests human parthenotes developed in vitro can differentiate into mature cells without a sperm centriole. AB - In most animals, somatic cell centrosomes are inherited from the centriole of the fertilizing spermatozoa. The oocyte centriole degenerates during oogenesis, and completely disappears in metaphase II. Therefore, the embryos generated by in vitro parthenogenesis are supposed to develop without any centrioles. Exceptional acentriolar and/or acentrosomal developments are possible in mice and in some experimental cells; however, in most animals, the full developmental potential of parthenogenetic cells in vitro and the fate of their centrioles/centrosomes are not clearly understood. To predict the future of in vitro human parthenogenesis, we explored the centrioles/centrosomes in ovarian mature cystic teratoma cells by immunofluorescent staining and transmission electron microscopy. We confirmed the presence of centrioles and centrosomes in these well-known parthenogenetic ovarian tumor cells. Our findings clearly demonstrate that, even without a sperm centriole, parthenotes that develop from activated oocytes can produce their own centrioles/centrosomes, and can even develop into the well-differentiated mature tissue. PMID- 22037460 TI - Oct4-related cytokine effects regulate tumorigenic properties of colorectal cancer cells. AB - Oct4, a member of the POU-domain transcription factor family, has been implicated in the cancer stem cell (CSC)-like properties of various cancers. However, the precise role of Oct4 in colorectal CSC initiation remains uncertain. Numerous studies have demonstrated a strong link between inflammation and tumorigenesis in colorectal cancers. In this study, we demonstrated that Oct4 overexpression enhances CSC-like properties of colorectal cancer cells (CRCs), including sphere formation, cell colony formation, cell migration, invasiveness, and drug resistance. In addition, putative CSC markers, stemness genes, drug-resistant genes, as well as interleukin (IL)-8 and IL-32 were upregulated. Microarray-based bioinformatics of CRCs showed higher expression levels of embryonic stem cell specific genes in cells that overexpressed Oct4. Neutralization of either IL-8 or IL-32 with specific antibodies partially blocked the tumorigenic effects induced by either Oct4 overexpression or by the addition of conditioned media from Oct4 overexpressing CRCs. In addition, the presence of Oct4-overexpressing CRCs enhanced the tumorigenic potential of parental CRCs in vivo. In summary, these data suggest that IL-8 and IL-32 play a role in regulating the CSC-like properties that promote tumorigenesis of CRCs in both autocrine and paracrine manners. PMID- 22037462 TI - Adaptor protein containing PH domain, PTB domain and leucine zipper (APPL1) regulates the protein level of EGFR by modulating its trafficking. AB - The EGFR-mediated signaling pathway regulates multiple biological processes such as cell proliferation, survival and differentiation. Previously APPL1 (adaptor protein containing PH domain, PTB domain and leucine zipper 1) has been reported to function as a downstream effector of EGF-initiated signaling. Here we demonstrate that APPL1 regulates EGFR protein levels in response to EGF stimulation. Overexpression of APPL1 enhances EGFR stabilization while APPL1 depletion by siRNA reduces EGFR protein levels. APPL1 depletion accelerates EGFR internalization and movement of EGF/EGFR from cell surface to the perinuclear region in response to EGF treatment. Conversely, overexpression of APPL1 decelerates EGFR internalization and translocation of EGF/EGFR to the perinuclear region. Furthermore, APPL1 depletion enhances the activity of Rab5 which is involved in internalization and trafficking of EGFR and inhibition of Rab5 in APPL1-depleted cells restored EGFR levels. Consistently, APPL1 depletion reduced activation of Akt, the downstream signaling effector of EGFR and this is restored by inhibition of Rab5. These findings suggest that APPL1 is required for EGFR signaling by regulation of EGFR stabilities through inhibition of Rab5. PMID- 22037461 TI - Proteomic analysis of lipid raft-enriched membranes isolated from internal organelles. AB - The mitochondria-associated membrane (MAM) is a sub-region of the endoplasmic reticulum (ER) that facilitates crosstalk between the ER and mitochondria. The MAM actively influences vital cellular processes including Ca(2+) signaling and protein folding. Detergent-resistant microdomains (DRMs) may localize proteins to the mitochondria/MAM interface to coordinate these events. However, the protein composition of DRMs isolated from this region is not known. Lipid-raft enriched DRMs were isolated from a combined mitochondria/MAM sample and analyzed using two dimensional reversed-phased tandem mass spectrometry. Strict post-acquisition filtering of the acquired data led to the confident identification 250 DRM proteins. The majority (58%) of the identified proteins are bona fide mitochondrial or ER proteins according to Gene Ontology annotation. Additionally, 74% of the proteins have previously been noted as MAM-resident or -associated proteins. Furthermore, ~20% of the identified proteins have a documented association with lipid rafts. Most importantly, known internal LR marker proteins (inositol 1,4,5-trisphosphate receptor type 3, erlin-2, and voltage-dependent anion channel 1) were detected as well as most of the components of the mitochondrial/MAM-localized Ca(2+) signaling complex. Our study provides the basis for future work probing how the protein activities at the mitochondrion/MAM interface are dependent upon the integrity of these internal lipid-raft-like domains. PMID- 22037463 TI - Hypoxia induced expression of histone lysine demethylases: implications in oxygen dependent retinal neovascular diseases. AB - Hypoxia inducible factor (HIF) plays a critical role in cellular adaptation to hypoxia by regulating the expression of essential genes. Pathological activation of this pathway leads to the expression of pro-angiogenic factors during the neovascularization in cancer and retinal diseases. Little is known about the epigenetic regulations during HIF-mediated transcription and activation of pro angiogenic genes in oxygen-dependent retinal diseases. Here, we show that hypoxia induces the expression of a number of histone lysine demethylases (KDMs) in retinal pigment epithelial cells. Moreover, we show that the expression of pro angiogenic genes (ADM, GDF15, HMOX1, SERPE1 and SERPB8) is dependent on KDMs under hypoxic conditions. Further, treating the cells with a general KDM inhibitor blocks the expression of these pro-angiogenic genes. Results from these studies identify a new layer of epigenetic transcription regulation under hypoxic conditions and suggest that specific inhibitors of KDMs such as JMJD1A can be a new therapeutic approach to treat diseases caused by the hypoxia induced neovascularization in cancer and retinal diseases. PMID- 22037464 TI - Transcriptional up-regulation of RhoE by hypoxia-inducible factor (HIF)-1 promotes epithelial to mesenchymal transition of gastric cancer cells during hypoxia. AB - Epithelial-mesenchymal transition (EMT) is a key process that drives cancer invasion. Recently, hypoxia has been reported to induce EMT, accompanied by cytoskeleton remodeling. As RhoE is a key regulator in cytoskeleton formation, we hypothesized that RhoE may play a role in hypoxia-induced EMT. For the first time, we report that RhoE protein levels increase in gastric cancer cells under hypoxic conditions. Rigorous analysis revealed that RhoE up-regulation is at the transcriptional levels and requires hypoxia-inducible factor (HIF)-1alpha induction, and that HIF-1alpha binds a hypoxia-responsive element (HRE) on the RhoE promoter. Additionally, we discovered that hypoxia or overexpression of RhoE in normoxia up-regulates the mesenchymal marker Vimentin, down-regulates the epithelial marker E-cadherin, and significantly increases cell invasion in vitro. Silencing of HIF-1alpha or RhoE by specific siRNAs rescued these hypoxia-induced effects. Ectopic expression of RhoE also induced up-regulation of MMP2/MMP-9 in gastric cancer cells. This study identifies RhoE as a direct target for HIF-1 in gastric cancer cells. In addition, RhoE up-regulation represents a pivotal cellular adaptive response to hypoxia with implications in gastric cancer cell EMT and invasion. We propose that RhoE-targeted therapy might inhibit the high invasive potential of gastric cancer cells in hypoxic regions. PMID- 22037465 TI - Epigenetic regulation of reproductive development and the emergence of apomixis in angiosperms. AB - Apomictic plants reproduce asexually through seeds by avoiding both meiosis and fertilization. While apomixis is genetically controlled, individual loci contributing to its expression have yet to be identified. Here, we review recent results indicating that RNA-dependent DNA methylation pathways acting during female reproduction are essential for proper reproductive development in plants, and may represent key regulators of the differentiation between apomictic and sexual reproduction. PMID- 22037466 TI - Subterranean space exploration: the development of root system architecture. AB - The colonisation of terrestrial environments offered plants a host of advantages. It also presented them with major challenges. The foremost amongst these, the dichotomous nature of terrestrial environments, was clearly successfully met by the development of an integrated but divergent root-shoot structure. Whereas they share many similarities, roots and shoots evolved specialist functions in line with their principle roles and their growth environment. In this review, we discuss a number of areas where recent discoveries, principally in Arabidopsis, are shedding light on the mechanisms that enable the successful colonisation of the soil environment. PMID- 22037467 TI - Structure of Fab fragment of malaria transmission blocking antibody 2A8 against P. vivax P25 protein. AB - Understanding the structural basis of recognition between antigen and antibody requires the structural comparison of free and complexed components. Previously, we have reported the crystal structure of the complex between Fab fragment of murine monoclonal antibody 2A8 (Fab2A8) and Plasmodium vivax P25 protein (Pvs25) at 3.2 A resolution. We report here the crystallization and X-ray structure of native Fab2A8 at 4.0 A resolution. The 2A8 antibody generated against Pvs25 prevents the formation of P. vivax oocysts in the mosquito, when assayed in membrane feeding experiment. Comparison of native Fab2A8 structure with antigen bound Fab2A8 structure indicates the significant conformational changes in CDR-H1 and CDR-H3 regions of V(H) domain and CDR-L3 region of V(L) domain of Fab2A8. Upon complex formation, the relative orientation between V(L) and V(H) domains of Fab2A8 is conserved, while significant differences are observed in elbow angles of heavy and light chains. The combing site residues of complexed Fab2A8 exhibited the reduced temperature factor compared to native Fab2A8, suggesting a loss of conformational entropy upon antigen binding. PMID- 22037468 TI - Coaggregation of amyloid fibrils for the preparation of stable and immobilized enzymes. AB - Highly stable enzyme coaggregates were developed using amyloid fibrils as support materials. Amyloid fibril formation was induced by ionic liquids, and immobilization was done by the coaggregation of enzymes and amyloid fibrils followed by chemical cross-linking. Transmission and scanning electron microscopy studies were carried out to characterize the coaggregates. The amyloid fibril linked enzymes showed significantly increased stability against various deactivating conditions. In addition, a high level of reusability was clearly observed. This study clearly demonstrated that amyloid fibrils can be used as biomaterials for enzyme immobilization and that amyloid fibril-linked enzyme coaggregates have good potential for industrial applications. PMID- 22037469 TI - Cofactor mobility determines reaction outcome in the IMPDH and GMPR (beta-alpha)8 barrel enzymes. AB - Inosine monophosphate dehydrogenase (IMPDH) and guanosine monophosphate reductase (GMPR) belong to the same structural family, share a common set of catalytic residues and bind the same ligands. The structural and mechanistic features that determine reaction outcome in the IMPDH and GMPR family have not been identified. Here we show that the GMPR reaction uses the same intermediate E-XMP* as IMPDH, but in this reaction the intermediate reacts with ammonia instead of water. A single crystal structure of human GMPR type 2 with IMP and NADPH fortuitously captures three different states, each of which mimics a distinct step in the catalytic cycle of GMPR. The cofactor is found in two conformations: an 'in' conformation poised for hydride transfer and an 'out' conformation in which the cofactor is 6 A from IMP. Mutagenesis along with substrate and cofactor analog experiments demonstrate that the out conformation is required for the deamination of GMP. Remarkably, the cofactor is part of the catalytic machinery that activates ammonia. PMID- 22037470 TI - Identifying polyglutamine protein species in situ that best predict neurodegeneration. AB - Polyglutamine (polyQ) stretches exceeding a threshold length confer a toxic function to proteins that contain them and cause at least nine neurological disorders. The basis for this toxicity threshold is unclear. Although polyQ expansions render proteins prone to aggregate into inclusion bodies, this may be a neuronal coping response to more toxic forms of polyQ. The exact structure of these more toxic forms is unknown. Here we show that the monoclonal antibody 3B5H10 recognizes a species of polyQ protein in situ that strongly predicts neuronal death. The epitope selectively appears among some of the many low molecular-weight conformational states assumed by expanded polyQ and disappears in higher-molecular-weight aggregated forms, such as inclusion bodies. These results suggest that protein monomers and possibly small oligomers containing expanded polyQ stretches can adopt a conformation that is recognized by 3B5H10 and is toxic or closely related to a toxic species. PMID- 22037471 TI - A de novo peptide hexamer with a mutable channel. AB - The design of new proteins that expand the repertoire of natural protein structures represents a formidable challenge. Success in this area would increase understanding of protein structure and present new scaffolds that could be exploited in biotechnology and synthetic biology. Here we describe the design, characterization and X-ray crystal structure of a new coiled-coil protein. The de novo sequence forms a stand-alone, parallel, six-helix bundle with a channel running through it. Although lined exclusively by hydrophobic leucine and isoleucine side chains, the 6-A channel is permeable to water. One layer of leucine residues within the channel is mutable, accepting polar aspartic acid and histidine side chains, which leads to subdivision and organization of solvent within the lumen. Moreover, these mutants can be combined to form a stable and unique (Asp-His)(3) heterohexamer. These new structures provide a basis for engineering de novo proteins with new functions. PMID- 22037472 TI - Genetic and functional studies implicate HIF1alpha as a 14q kidney cancer suppressor gene. AB - Kidney cancers often delete chromosome 3p, spanning the VHL tumor suppressor gene, and chromosome 14q, which presumably harbors >= 1 tumor suppressor genes. pVHL inhibits the hypoxia-inducible transcription factor (HIF), and HIF2alpha is a kidney cancer oncoprotein. In this article, we identify focal, homozygous deletions of the HIF1alpha locus on 14q in clear cell renal carcinoma cell lines. Wild-type HIF1alpha suppresses renal carcinoma growth, but the products of these altered loci do not. Conversely, downregulation of HIF1alpha in HIF1alpha proficient lines promotes tumor growth. HIF1alpha activity is diminished in 14q deleted kidney cancers, and all somatic HIF1alpha mutations identified in kidney cancers tested to date are loss of function. Therefore, HIF1alpha has the credentials of a kidney cancer suppressor gene. SIGNIFICANCE: Deletion of 14q is a frequent event in clear cell renal carcinoma and portends a poor prognosis. In this study, we provide genetic and functional evidence that HIF1alpha is a target of 14q loss in kidney cancer. PMID- 22037473 TI - Evolutionary history of a widespread Indo-Pacific goby: the role of Pleistocene sea-level changes on demographic contraction/expansion dynamics. AB - Compared to endemics, widespread species are of particular interest to retrace recent evolutionary history. These species have a large population size which provides a clearer genetic signature of past events. Moreover, their wide geographic range increases the potential occurrence of evolutionary events (expansion, divergence, etc.). Here, we used several coalescent-based methods to disentangle the evolutionary history of a widespread amphidromous goby (Sicyopterus lagocephalus), in the light of sea-level variations during the Pleistocene. Using 75 samples recovered from three biogeographic regions (Western Indian Ocean, Melanesia and Polynesia), we analysed a portion of the cytochromeb gene and confirmed three major haplogroups, each specific to a region. Furthermore, we found that: (1) the Melanesian haplogroup was the oldest while the two peripheral regions hosted daughter haplogroups; (2) two centrifugal colonisation events occurred from Melanesia to the periphery, each synchronised with periods of strong paleo-ENSO episodes; (3) the demographic contraction expansion events were linked to Pleistocene sea-level changes; (4) Melanesia and Polynesia acted as efficient refuges during the Last Glacial Maximum. These results highlight the importance of studying widespread species to better understand the role of climate changes and paleo-oceanography on the evolution of biodiversity. PMID- 22037474 TI - Preparation and optimization of PMAA-chitosan-PEG nanoparticles for oral drug delivery. AB - The objective of this study was to develop pH sensitive polymethacrylic acid chitosan-polyethylene glycol (PCP) nanoparticles. This was achieved by dispersion polymerization of methacrylic acid (MAA), polyethylene glycol (PEG) and different chitosan (CS) grades in the presence of cross linking agent ethylene dimethacrylate (EDMA) and polymer initiator potassium persulphate. Method development was carried out by varying formulation parameters such as type of CS, ratio of PEG to CS, quantity of solvent and polymer initiator. Metoprolol (MTP) tartrate was incorporated into the nanoparticles (NPs) as a model drug. Laser diffraction, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies revealed that the NPs were spherical with smooth surfaces ranging in size from 190 to 450 nm. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) findings showed the presence of amorphous MTP in PCP NPs. The MTP loading of PCP and glycol chitosan (GC) NPs varied from 10 to 45% depending on the CS grade while both types of NPs showed excellent binding efficiency on mucin from porcine stomach. The in vitro dissolution study showed pH dependent release profiles suggesting that the PCP NPs system have great potential for oral controlled drug delivery as an alternative to conventional dosage forms. PMID- 22037475 TI - Implications of the alpha dispersion for studies on interaction of tobacco smoke- corneal tissue. AB - In this work, we have carried out a dielectric study to determine the effect of tobacco smoke on the rat corneal function. Measurements were performed over the frequency range of 500 Hz-100 kHz in air and at the temperature of 35 degrees C. The frequency dependencies of the loss tangent for both healthy and smoky cornea exhibit two peaks with different width occurring as a narrow at 2 kHz and a broad at around 16 kHz. The distribution parameter alpha at 2 kHz has a value of about 0.3, which increases to 0.6 at 16 kHz. The magnitude of the permittivity decrement at 2 and 16 kHz is about two and four times higher, respectively, for the smoky cornea than that for the healthy one. These dielectric studies indicate that the present method is useful in detection of the effect of tobacco smoke exposure on the corneal behavior. PMID- 22037476 TI - Bilirubin adsorption properties of water-soluble adsorbents with different cyclodextrin cavities in plasma dialysis system. AB - In this study, we explored the use of alpha-, beta- or gamma-cyclodextrin (CD) grafted polyethyleneimine (PEI) as water-soluble adsorbent for removing excess plasma bilirubin. To evaluate the bilirubin-binding capacity of these adsorbents, bovine serum albumin (BSA) solution or plasma with high level of bilirubin were dialyzed against CD-PEI-spiked dialysate. In BSA solution with an initial biliurbin concentration of 171.5mg/L, alpha-CD-PEI, beta-CD-PEI and gamma-CD-PEI achieved adsorption capacities of 2.5, 5.8 and 3.8 mg/g, respectively. In a plasma dialysis system, 45.6% of bilirubin (260 mg/L) was removed from 200 mL plasma by 1L dialysate spiked with 10mg/mL beta-CD-PEI, which was significantly higher than that removed by the same volume of BSA-spiked dialysate (P<0.05), demonstrating the strong bilirubin-binding ability of beta-CD-PEI. The key feature of bilirubin adsorption was related to the CD functional group, not the PEI matrix. Subsequent molecular docking study indicated that the size of CD cavity could affect the affinity energy of CD-bilirubin complex. The cavity of beta-CD was most suitable for accommodating the pyrrole rings of bilirubin. The inclusion complex of bilirubin and beta-CD in the molar ratio of 1:2 was more logical in terms of affinity energy. All the results demonstrated the potential of beta-CD-PEI (water-soluble adsorbent) as an effective agent for removing of bilirubin from plasma in dialysis system. PMID- 22037478 TI - TBHP-mediated oxidative thiolation of an sp3 C-H bond adjacent to a nitrogen atom in an amide. AB - The first example of molecular sieve-promoted TBHP-mediated direct oxidative thiolation of an sp(3) C-H bond adjacent to a nitrogen atom with disulfides under metal-free conditions, which allows for preparation of numerous S,N-containing compounds, is presented. Moreover, diverse benzothiazoles and a fipronil analog can be synthesized through this strategy. PMID- 22037477 TI - Effects of middle-ear disorders on power reflectance measured in cadaveric ear canals. AB - OBJECTIVE: Reflectance measured in the ear canal offers a noninvasive method to monitor the acoustic properties of the middle ear, and few systematic measurements exist on the effects of various middle-ear disorders on the reflectance. This work uses a human cadaver-ear preparation and a mathematical middle-ear model to both measure and predict how power reflectance R is affected by the middle-ear disorders of static middle-ear pressures, middle-ear fluid, fixed stapes, disarticulated incudostapedial joint, and tympanic-membrane perforations. DESIGN: R was calculated from ear-canal pressure measurements made on human-cadaver ears in the normal condition and five states: (1) positive and negative pressure in the middle-ear cavity, (2) fluid-filled middle ear, (3) stapes fixed with dental cement, (4) incudostapedial joint disarticulated, and (5) tympanic-membrane perforations. The middle-ear model of Kringlebotn (1988) was modified to represent the middle-ear disorders. Model predictions are compared with measurements. RESULTS: For a given disorder, the general trends of the measurements and model were similar. The changes from normal in R, induced by the simulated disorder, generally depend on frequency and the extent of the disorder (except for the disarticulation). Systematic changes in middle-ear static pressure (up to 6300 daPa) resulted in systematic increases in R. These affects were most pronounced for frequencies up to 1000 to 2000 Hz. Above about 2000 Hz there were some asymmetries in behavior between negative and positive pressures. Results with fluid in the middle-ear air space were highly dependent on the percentage of the air space that was filled. Changes in R were minimal when a smaller fraction of the air space was filled with fluid, and as the air space was filled with more saline, R increased at most frequencies. Fixation of the stapes generally resulted in a relatively small low-frequency increase in R. Disarticulation of the incus with the stapes led to a consistent low-frequency decrease in R with a distinctive minimum below 1000 Hz. Perforations of the tympanic membrane resulted in a decrease in R for frequencies up to about 2000 Hz; at these lower frequencies, smaller perforations led to larger changes from normal when compared with larger perforations. CONCLUSIONS: These preliminary measurements help assess the utility of power reflectance as a diagnostic tool for middle-ear disorders. In particular, the measurements document (1) the frequency ranges for which the changes are largest and (2) the extent of the changes from normal for a spectrum of middle-ear disorders. PMID- 22037479 TI - Evolution from a localized to an intermediate valence regime in Ce2Cu(2 x)Ni(x)In. AB - Polycrystalline samples of the solid solution Ce2Cu(2-x)Ni(x)In were studied by means of x-ray powder diffraction, magnetic susceptibility and electrical resistivity measurements performed in a wide temperature range. Partial substitution of copper atoms by nickel atoms results in a quasi-linear decrease of the lattice parameters and the unit cell volume of the system. The lattice compression leads to an increase in the exchange integral and yields a reversal in the order of the magnetic 4f(1) and nonmagnetic 4f(0) states, being in line with the Doniach phase diagram. In the localized regime, where an interplay of the Kondo scattering and the crystalline electric field effect occurs, the rise in the hybridization strength is accompanied by a relative reduction in the scattering conduction electrons on excited crystal field levels. PMID- 22037480 TI - A comprehensive analysis of fifteen genes of steviol glycosides biosynthesis pathway in Stevia rebaudiana (Bertoni). AB - Stevia [Stevia rebuaidana (Bertoni); family: Asteraceae] is known to yield diterpenoid steviol glycosides (SGs), which are about 300 times sweeter than sugar. The present work analyzed the expression of various genes of the SGs biosynthesis pathway in different organs of the plant in relation to the SGs content. Of the various genes of the pathway, SrDXS, SrDXR, SrCPPS, SrKS, SrKO and three glucosyltransferases namely SrUGT85C2, SrUGT74G1 and SrUGT76G1 were reported from stevia. Here, we report cloning of seven additional full-length cDNA sequences namely, SrMCT, SrCMK, SrMDS, SrHDS, SrHDR, SrIDI and SrGGDPS followed by expression analysis of all the fifteen genes vis-a-vis SGs content analysis. SGs content was highest in the leaf at 3rd node position (node position with reference to the apical leaf as the first leaf) as compared to the leaves at other node positions. Except for SrDXR and SrKO, gene expression was maximum in leaf at 1st node and minimum in leaf at 5th node. The expression of SrKO was highest in leaf at 3rd node while in case of SrDXR expression showed an increase up to 3rd leaf and decrease thereafter. SGs accumulated maximum in leaf tissue followed by stem and root, and similar was the pattern of expression of all the fifteen genes. The genes responded to the modulators of the terpenopids biosynthesis. Gibberellin (GA(3)) treatment up-regulated the expression of SrMCT, SrCMK, SrMDS and SrUGT74G1, whereas methyl jasmonate and kinetin treatment down regulated the expression of all the fifteen genes of the pathway. PMID- 22037481 TI - Identification and functional characterization of novel compound heterozygotic mutations in the TECTA gene. AB - Mutations of the TECTA gene, which encodes alpha-tectorin, are associated with both dominant (DFNA8/A12) and recessive (DFNB 21) modes of inherited nonsyndromic sensorineural hearing loss, respectively. Although clinical data and genetic analysis for TECTA gene have been reported from different groups, there is no report that compound heterozygous mutations in the TECTA gene result in nonsyndromic sensorineural hearing loss. Here, we identified a missense mutation (p.C1691F) and a splicing mutation (c.6162+3insT), one in each TECTA allele, in the patient with hearing loss. Also, we demonstrated that the splicing mutation results in the abnormal skipping of an exon, which leads to a truncated protein as determined by exon-trapping analysis. To the best of our knowledge, this is the first report of an in vitro functional study of splice site mutations in the TECTA gene. PMID- 22037482 TI - Molecular mining of GGAA tagged transcripts and their expression in water buffalo Bubalus bubalis. AB - Repeat sequences are involved in regulation of gene expression both at the transcriptional and translational level. In the mammalian genomes, tri- and tetranucleotide repeats like ATA, AATA, GGAA and GAAA have been associated with diseases. In silico analysis of (GGAA)5 distribution across the species showed maximum number of this repeat in the mouse transcriptome compared to that in other species. Following this, we conducted minisatellite associated sequence amplification (MASA) to explore the buffalo's transcriptome using cDNA from different tissues and an oligo based on (GGAA)5 repeats. MASA uncovered twenty six mRNA transcripts showing homology to known genes in the database. qPCR studies showed the highest expression of twelve transcripts in the spleen. A transcript, pLRC107 with its partial sequence of 203 nucleotides showed sequence variation at several positions in spleen as compared to other four tissues examined. Transcript pLRC100 was found to represent the partial coding sequence of Bos taurus HECT {(homologous to E6-associated protein (UBE3A) carboxyl terminus domain) and RCC1 (CHC1)-like domain (RLD) 1}, mRNA. We ascertained full length coding sequence of HECT gene and localized the same on buffalo chromosome 10 employing FISH. This gene was found to be conserved across the species. Another gene LRP8 uncovered in the process showed copy number variation between buffalo males (4-9) and females (34-54). The MASA approach enabled us to identify several genes in Bubalus bubalis without screening an entire cDNA library. The highest expression of 12 mRNA transcripts in spleen suggests their likely involvement with immuno transaction. A comprehensive knowledge of the repeat tagged transcriptomes is envisaged to help in understanding their significance in genome organization and evolution forming rich basis of functional and comparative genomics. PMID- 22037483 TI - Up-regulation of osteopontin expression by aryl hydrocarbon receptor via both ligand-dependent and ligand-independent pathways in lung cancer. AB - The secreted glycol-phosphoprotein OPN not only plays important roles in immune responses and tissue remodeling but is also intimately involved in tumorigenesis. It is up-regulated in various cancers and correlated with poor prognosis. It is evident by enhancing growth and migration of cancer cells. However, the mechanisms that participate in up-regulation of OPN in lung cancer are largely unknown. Up-regulation of aryl hydrocarbon receptor (AhR), a transcription factor activated by xenobiotics, has been observed in lung cancer as well as premalignant lesions. In this study we demonstrated that AhR positively regulates OPN expression in lung cancer. We observed positive correlation of OPN and AhR expression in lung cancer specimen. Knockdown or overexpression of AhR exhibited down- or up-regulation of OPN expression in lung cancer cells. We identified an OPN promoter region between positions -268 and +435 that was activated by both ligand-independent and ligand-activated AhR. However, this region does not contain AhR response element/dioxin response element (DRE/XRE). Further truncations and internal deletions of the promoter revealed that the ligand independent and ligand-activated AhR function through different regions of OPN promoter. The region between -268 and -100 was required for ligand-independent AhR activity. This region contains several cis-elements including AP2, C/EBP, SP1 and AP1 sites. On the other hand, the ligand-activated AhR up-regulates OPN activity through two regions of OPN promoter; one contains NFkappaB site at +137 and the other is between positions -100 and +126. This study suggested that both overexpression of un-induced AhR (in cases of non-smokers with high level of AhR) and ligand-activated AhR (such as smokers) contribute to up-regulation of OPN that in turn leads to lung tumorigenesis. PMID- 22037485 TI - nanog 5'-upstream sequence, DNA methylation, and expression in gametes and early embryo reveal striking differences between teleosts and mammals. AB - The nanog gene plays a major role in vertebrate development and was only recently discovered in teleosts. In order to gain new insight into its regulation in gametes and early embryo in teleost fish, the present study aimed at characterizing nanog upstream sequence features and DNA methylation, as well as early embryonic expression pattern in a Cyprinid fish, the goldfish. Using an in silico approach, we were able to demonstrate that despite the existence of conserved regulatory motifs in the promoter region of the nanog gene, specific features known to play a major role in the regulation of Nanog in mammals were missing in teleosts. The analysis of CpG sites in the upstream region of the nanog genes in goldfish revealed a significant DNA methylation state in oocytes while a hypomethylated state was observed in sperm. Using both quantitative PCR and whole mount in situ hybridization, we were able to clearly demonstrate the maternal inheritance of the nanog transcript in goldfish. Corresponding mRNA levels subsequently decreased during early gastrulation. Together, our results reveal striking differences in expression and DNA methylation patterns in gametes and during early development and in upstream region features between teleosts and mammals that are consistent with the hypothesis of a rapid evolution of the Nanog gene in vertebrates, at least in some lineages. PMID- 22037484 TI - Identification and functional characterization of the human EXT1 promoter region. AB - BACKGROUND: Mutations in Exostosin-1 (EXT1) or Exostosin-2 (EXT2) cause the autosomal dominant disorder multiple osteochondromas (MO). This disease is mainly characterized by the appearance of multiple cartilage-capped protuberances arising from children's metaphyses and is known to display clinical inter- and intrafamilial variations. EXT1 and EXT2 are both tumor suppressor genes encoding proteins that function as glycosyltransferases, catalyzing the biosynthesis of heparan sulfate. At present, however, very little is known about the regulation of these genes. Two of the most intriguing questions concerning the pathogenesis of MO are how disruption of a ubiquitously expressed gene causes this cartilage specific disease and how the clinical intrafamilial variation can be explained. Since mutations in the EXT1 gene are responsible for ~65% of the MO families with known causal mutation, our aim was to isolate and characterize the EXT1 promoter region to elucidate the transcriptional regulation of this tumor suppressor gene. METHODS: In the present study, luciferase reporter gene assays were used to experimentally confirm the in silico predicted EXT1 core promoter region. Subsequently, we evaluated the effect of single nucleotide polymorphisms (SNP's) on EXT1 promoter activity and transcription factor binding using luciferase assays, electrophoretic mobility shift assays (EMSA), and enzyme-linked immunosorbent assays (ELISA). Finally, a genotype-phenotype study was performed with the aim to identify one or more genetic modifiers influencing the clinical expression of MO. RESULTS: Transient transfection of HEK293 cells with a series of luciferase reporter constructs mapped the EXT1 core promoter at approximately 917 bp upstream of the EXT1 start codon, within a 123 bp region. This region is conserved in mammals and located within a CpG-island containing a CAAT- and a GT box. A polymorphic G/C-SNP at -1158 bp (rs34016643) was demonstrated to be located in a USF1 transcription factor binding site, which is lost with the presence of the C-allele resulting in a ~56% increase in EXT1 promoter activity. A genotype-phenotype study was suggestive for association of the C-allele with shorter stature, but also with a smaller number of osteochondromas. CONCLUSIONS: We provide for the first time insight into the molecular regulation of EXT1. Although a larger patient population will be necessary for statistical significance, our data suggest the polymorphism rs34016643, in close proximity of the EXT1 promoter, to be a potential regulatory SNP, which could be a primary modifier that might explain part of the clinical variation observed in MO patients. PMID- 22037486 TI - Microdeletion and microduplication 17q21.31 plus an additional CNV, in patients with intellectual disability, identified by array-CGH. AB - The recognition of the 17q21.31 microdeletion and microduplication syndrome has been facilitated by high resolution oligonucleotide array comparative genome hybridization technology (aCGH). Molecular analysis of the 17q21.31 microdeletion/duplication syndrome demonstrated a critical region involving at least six genes, including STH and MAPT. The 17q21.31 microdeletion syndrome has an incidence of 1 in 16,000 births, while the microduplication 17q21.31 has been reported so far in only five patients. In general, phenotypes associated with 17q21.31 microduplication seem to be milder than those associated with the microdeletion. Here, we present four patients who have been referred for genetic evaluation by clinical geneticists due to developmental delay and minor congenital abnormalities. Previous standard karyotypes were negative, while aCGH analysis revealed three patients with 17q21.31 microdeletion and one with the respective microduplication, being the sixth reported case so far. Most importantly one of the microdeletion cases involves only partial MAPT gene deletion while leaving the STH gene intact. Two of our patients, one with the 17q21.31 microdeletion and another with the respective microduplication, carried additional clinically relevant microdeletions (del Xq21.31 and del 15q11.2, respectively), possibly modifying their phenotype. PMID- 22037487 TI - Identification and characterization of splicing variants of PLEKHA5 (Plekha5) during brain development. AB - PLEKHA5 (pleckstrin homology domain-containing protein family A, member 5) belongs to the PLEKHA family (PLEKHA1-6); however, the properties of this protein remain poorly characterized. We have identified and characterized two forms of PLEKHA5 mRNA. The long form of PLEKHA5 (L-PLEKHA5) contains 32 exons, encodes 1282 amino acids, and is specifically expressed in the brain; the short form of PLEKHA5 (S-PLEKHA5) is generated by alternative splicing of L-PLEKHA5, contains 26 exons, encodes 1116 amino acids, and is ubiquitously expressed. Both forms of the protein contain putative Trp-Trp (WW) and pleckstrin homology (PH) domains and are located mainly in the cytosol. Developmental and age-dependent expression studies in the mouse brain have shown that Plekha5 is the most abundantly expressed protein at E13.5 with S-Plekha5 dominancy. L-Plekha5 levels increased gradually with the decrease in total Plekha5 levels; moreover, L-Plekha5 became the dominant protein at E17.5, maintaining its dominance throughout adulthood. Protein-lipid overlay assays have indicated that the PH domain of PLEKHA5 specifically interacts with PI3P, PI4P, PI5P, and PI(3,5)P2. These results suggest that the S- to L-conversion of PLEKHA5 (Plekha5) may play an important role in brain development through association with specific phosphoinositides. PMID- 22037488 TI - The life cycle of Asymphylodora perccotti sp. n. (Trematoda: Lissorchiidae) in the Russian Southern Far East. AB - Specimens of Asymphylodora perccotti sp. n. (Trematoda: Lissorchidae) were found in the esophagus of the freshwater fish Perccottus glenii (Odobantidae) taken from the Bolshaya Ussurka River Basin (Primorsky Region, Russian Southern Far East). The first intermediate host of this trematode is a gastropod, Parafossarulus manchouricus, and the secondary hosts are the same mollusk and Boreoelona ussuriensis. Specimens of the new species are similar to A. amnicolae identified by Stunkard in 1959, but the mature worms have larger suckers and shorter ceca. The cercariae of these species are distinguished by body, suckers and pharynx size. These organs in A. perccotti sp. n. are more than one-third larger than what is observed in A. amnicolae. In addition, the new species lacks the capacity for progenesis. Finally, the new species is unusual in that it resides in the fish esophagus instead of the intestine, as is common for most Asymphylodora species. Partial ribosomal DNA sequences and phylogenetic reconstruction sequence data indicate that these worms represent a new digenean species. PMID- 22037489 TI - Mutual cancellation between tones presented by air conduction, by bone conduction and by non-osseous (soft tissue) bone conduction. AB - Auditory sensation can be elicited not only by air conducted (AC) sound or bone conducted (BC) sound, but also by stimulation of soft tissue (STC) sites on the head and neck relatively distant from deeply underlying bone. Tone stimulation by paired combinations of AC with BC (mastoid) and/or with soft tissue conduction produce the same pitch sensation, mutual masking and beats. The present study was designed to determine whether they can also cancel each other. The study was conducted on ten normal hearing subjects. Tones at 2 kHz were presented in paired combinations by AC (insert earphone), by BC (bone vibrator) at the mastoid, and by the same bone vibrator to several STC sites; e.g. the neck, the sterno-cleido mastoid muscle, the eye, and under the chin, shifting the phases between the pairs. Subjects reported changes in loudness and cancellation. The phase for cancellation differed across subjects. Neck muscle manipulations (changes in head position) led to alterations in the phase at which cancellation was reported. Cancellation was also achieved between pairs of tones to two STC sites. The differing phases for cancellation across subjects and the change in phase accompanying different head positions may be due to the different acoustic impedances of the several tissues in the head and neck. A major component of auditory stimulation by STC may not induce actual skull bone vibrations and may not involve bulk fluid volume displacements. PMID- 22037490 TI - GFR prediction from cystatin C and creatinine in children: effect of including body cell mass. AB - BACKGROUND: Aiming to develop a more accurate cystatin C-based model for estimation of glomerular filtration rate (GFR) in children, we hypothesized that inclusion of body cell mass (BCM) would increase the accuracy of the GFR estimate in comparison to a well-established GFR reference method. STUDY DESIGN: Diagnostic test accuracy study. SETTINGS & PARTICIPANTS: 119 children (mean age, 8.8; range, 2.3-14.9 years) referred for GFR measurement by chromium 51 ethylenediaminetetraacetic acid ((51)Cr-EDTA) clearance (mean GFR, 98; range, 13.7-147.4 mL/min/1.73 m(2)). INDEX TEST: GFR estimations by the 2 prediction models resulting from theoretical considerations corroborated by forward stepwise variable selection: GFR (mL/min) = 0.542 * (BCM/SCysC)(0.40) * (height * BSA/SCr)(0.65) and GFR (mL/min) = 0.426 * (weight/SCysC)(0.39) * (height * BSA/SCr)(0.64), where SCysC is serum cystatin C level, BSA is body surface area, and SCr is serum creatinine level. The accuracy and precision of these models were compared with 7 previously published prediction models using random subsampling cross-validation. Local constants and coefficients were calculated for all models. Root mean square error, R(2), and percentage of predictions within +/-10% and +/-30% of the reference GFR were calculated for all models. Based on 1,000 runs of the cross-validation procedure, median values and 2.5th and 97.5th quantiles of the validation parameters were calculated. REFERENCE TEST: GFR measurement by (51)Cr-EDTA clearance. RESULTS: The BCM model predicted 98% within +/-30% of reference GFR and 66% within +/-10%, which was higher than for any other model. The weight model predicted 97.5% within +/-30% of reference GFR and 62% within +/-10%. The BCM model had the highest R(2) and the smallest root mean square error. LIMITATIONS: Included only 9 children with GFR <60 mL/min/1.73 m(2). Lack of independent validation cohort. CONCLUSIONS: The novel BCM model predicts GFR with higher accuracy than previously published models. The weight model is almost as accurate as the BCM model and allows for GFR estimation without knowledge of BCM. However, endogenous methods are still not sufficiently accurate to replace exogenous markers when GFR must be determined with high accuracy. PMID- 22037491 TI - Complications following 573 percutaneous renal radiofrequency and cryoablation procedures. AB - PURPOSE: To review complications related to percutaneous renal tumor ablation. MATERIALS AND METHODS: Prospectively collected data related to renal radiofrequency (RF) ablation and cryoablation procedures performed from May 2000 through November 2010 were reviewed. This included 573 renal ablation procedures performed in 533 patients to treat 633 tumors. A total of 254 RF ablation and 311 cryoablation procedures were performed; eight patients underwent simultaneous RF ablation and cryoablation. The mean age of patients at the time of the procedure was 70 years (range, 24-93 y), and 382 of 573 procedures (67%) were performed in male patients. Complications were recorded according to the Clavien-Dindo classification scheme. Duration of hospitalization was also documented. RESULTS: Of the 573 procedures, 63 produced complications (11.0% overall complication rate). There were 66 reported complications, of which 38 (6.6% of total procedures) were Clavien-Dindo grade II-IV major complications; there were no deaths. Major complication rates did not differ statistically (P = .15) between cryoablation (7.7%; 24 of 311) and RF ablation (4.7%; 12 of 254). Of the complications related to cryoablation, bleeding and hematuria were most common. Bleeding during cryoablation was associated with advanced age, increased tumor size, increased number of cryoprobes, and central position (P < .05). Of those treated with RF ablation, nerve and urothelial injury were most common. Mean hospitalization duration was 1 day for RF ablation and cryoablation. CONCLUSIONS: Complications related to percutaneous renal ablation are infrequent. Recognition of potential complications and associated risk factors can allow optimization of periprocedural care. PMID- 22037492 TI - Bacterial inclusion bodies: making gold from waste. AB - Many protein species produced in recombinant bacteria aggregate as insoluble protein clusters named inclusion bodies (IBs). IBs are discarded from further processing or are eventually used as a pure protein source for in vitro refolding. Although usually considered as waste byproducts of protein production, recent insights into the physiology of recombinant bacteria and the molecular architecture of IBs have revealed that these protein particles are unexpected functional materials. In this Opinion article, we present the relevant mechanical properties of IBs and discuss the ways in which they can be explored as biocompatible nanostructured materials, mainly, but not exclusively, in biocatalysis and tissue engineering. PMID- 22037493 TI - Current needs and future directions of occupational safety and heath in a globalized world. AB - This summary provides a synopsis of talks included in a symposium entitled "Current Needs and Future Directions of Occupational Safety and Heath in a Globalized World". The purpose of the symposium was to (1) highlight national and international agencies with occupational health related activities; (2) address electronic (e-)waste issues in developing countries where exposures are secondary to the handling and scavenging of scrap; and (3) discuss the effects of hazardous materials, such as polycyclic aromatic hydrocarbon (PAH) and tobacco smoke on child intelligence quotient (IQ) in developing countries. PMID- 22037494 TI - Effects of methylmercury on the secretion of pro-inflammatory cytokines from primary microglial cells and astrocytes. AB - Glial cells, including oligodendrocytes, astrocytes and microglia are important to proper central nervous system (CNS) function. Deregulation or changes to CNS populations of astrocytes and microglia in particular are expected to play a role in many neurodegenerative diseases, including Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). Previous studies have reported methylmercury (MeHg) induced changes in glial cell function; however, the effects of MeHg on these cells remains poorly understood. This study aims to examine the effect of MeHg on the secretion of pro-inflammatory cytokines from microglia and astrocytes. The impact of the microglia/astrocyte ratio on cytokine secretion was also examined. Microglia and astrocytes were cultured from the brains of neo-natal BALB/C mice and dosed with MeHg (0-1 MUM) and stimulated with PAM(3)CSK(4) (PAM(3)), a toll-like receptor (TLR) ligand. After this, the secretion of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1beta) was measured by ELISA. MeHg reduced the secretion of IL-6 in a dose dependant manner but did not effect the secretion of TNF-alpha. No change in IL-1beta was observed in any treatments, indicating that PAM(3) cannot induce the secretion of this cytokine from glial cells. Additionally, the ratio of microglia/astrocyte had an effect on the secretion of IL-6 but not TNF alpha. These results indicate that MeHg can modify the response of glial cells and the interactions with astrocytes can affect the response of the microglia cells in culture. These results are significant in understanding the potential relationship with MeHg and neurodegenerative diseases and for the interpretation of results of future in vitro studies using monoculture. PMID- 22037495 TI - Structural organization of intercellular channels II. Amino terminal domain of the connexins: sequence, functional roles, and structure. AB - The amino terminal domain (NT) of the connexins consists of their first 22-23 amino acids. Site-directed mutagenesis studies have demonstrated that NT amino acids are determinants of gap junction channel properties including unitary conductance, permeability/selectivity, and gating in response to transjunctional voltage. The importance of this region has also been emphasized by the identification of multiple disease-associated connexin mutants affecting amino acid residues in the NT region. The first part of the NT is alpha-helical. The structure of the Cx26 gap junction channel shows that the NT alpha-helix localizes within the channel, and lines the wall of the pore. Interactions of the amino acid residues in the NT with those in the transmembrane helices may be critical for holding the channel open. The predicted sites of these interactions and the applicability of the Cx26 structure to the NT of other connexins are considered. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. PMID- 22037496 TI - 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging. AB - DNA methylation dynamics influence brain function and are altered in neurological disorders. 5-hydroxymethylcytosine (5-hmC), a DNA base that is derived from 5 methylcytosine, accounts for ~40% of modified cytosine in the brain and has been implicated in DNA methylation-related plasticity. We mapped 5-hmC genome-wide in mouse hippocampus and cerebellum at three different ages, which allowed us to assess its stability and dynamic regulation during postnatal neurodevelopment through adulthood. We found developmentally programmed acquisition of 5-hmC in neuronal cells. Epigenomic localization of 5-hmC-regulated regions revealed stable and dynamically modified loci during neurodevelopment and aging. By profiling 5-hmC in human cerebellum, we found conserved genomic features of 5 hmC. Finally, we found that 5-hmC levels were inversely correlated with methyl CpG-binding protein 2 dosage, a protein encoded by a gene in which mutations cause Rett syndrome. These data suggest that 5-hmC-mediated epigenetic modification is critical in neurodevelopment and diseases. PMID- 22037497 TI - The conundrums of understanding genetic risks for autism spectrum disorders. AB - Recent advances in the genetics of autism spectrum disorders (ASDs) are offering new valuable insights into molecular and cellular mechanisms of pathology. At the same time, the emerging data challenge long-standing diagnostic conventions and the notion of phenotypic specificity. This review addresses the particular issues that attend gene discovery in neuropsychiatric and neurodevelopmental disorders and ASDs in particular, summarizes recent findings in human genetics broadly that are driving the reevaluation of the conventional wisdom regarding the allelic architecture of common psychiatric conditions, reviews selected discoveries in ASDs and their relevance to models of pathology, highlights the conceptual and practical issues raised by the observation of a convergence of ASD genetic risks with distinct psychiatric disorders, and considers the important interplay of studies of neurobiology and genetics in clarifying and extending our understanding of social disability syndromes. PMID- 22037498 TI - Double dissociation of value computations in orbitofrontal and anterior cingulate neurons. AB - Damage to prefrontal cortex (PFC) impairs decision-making, but the underlying value computations that might cause such impairments remain unclear. Here we report that value computations are doubly dissociable among PFC neurons. Although many PFC neurons encoded chosen value, they used opponent encoding schemes such that averaging the neuronal population extinguished value coding. However, a special population of neurons in anterior cingulate cortex (ACC), but not in orbitofrontal cortex (OFC), multiplexed chosen value across decision parameters using a unified encoding scheme and encoded reward prediction errors. In contrast, neurons in OFC, but not ACC, encoded chosen value relative to the recent history of choice values. Together, these results suggest complementary valuation processes across PFC areas: OFC neurons dynamically evaluate current choices relative to recent choice values, whereas ACC neurons encode choice predictions and prediction errors using a common valuation currency reflecting the integration of multiple decision parameters. PMID- 22037499 TI - Modulation of dADAR-dependent RNA editing by the Drosophila fragile X mental retardation protein. AB - Loss of FMR1 gene function results in fragile X syndrome, the most common heritable form of intellectual disability. The protein encoded by this locus (FMRP) is an RNA-binding protein that is thought to primarily act as a translational regulator; however, recent studies have implicated FMRP in other mechanisms of gene regulation. We found that the Drosophila fragile X homolog (dFMR1) biochemically interacted with the adenosine-to-inosine RNA-editing enzyme dADAR. Adar and Fmr1 mutant larvae exhibited distinct morphological neuromuscular junction (NMJ) defects. Epistasis experiments based on these phenotypic differences revealed that Adar acts downstream of Fmr1 and that dFMR1 modulates dADAR activity. Furthermore, sequence analyses revealed that a loss or overexpression of dFMR1 affects editing efficiency on certain dADAR targets with defined roles in synaptic transmission. These results link dFMR1 with the RNA editing pathway and suggest that proper NMJ synaptic architecture requires modulation of dADAR activity by dFMR1. PMID- 22037500 TI - Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors. AB - Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal. PMID- 22037502 TI - Rat detrusor overactivity induced by chronic spinalization can be abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist. AB - PURPOSE: To evaluate the effect of a transient receptor potential vanilloid 1 (TRPV1) antagonist GRC 6211 on neurogenic detrusor overactivity (NDO) of spinal origin. MATERIALS AND METHODS: Cystometries under urethane anaesthesia were obtained in 14 chronic spinalized rats to confirm NDO. Two groups were created. In the first one (n=10), GRC 6211 (0.01, 0.1 and 1mg/kg weight) was administered via the duodenum in cumulative doses and cystometries performed 150 min after the administration of each dose of the drug. In the second group (n=4), used as control, the animals were submitted to cystometries during 12 hours, without administration of GRC 6211. Frequency and amplitude of bladder contractions were recorded in both groups. RESULTS: The mean (+/-SDev) bladder detrusor muscle contraction frequency of spinalized rats was 0.7+/-0.27 contractions/min. GRC 6211 produced a significant dose-dependent effect, with the frequency diminished to 0.53+/-0.23, 0.40+/-0.20 and 0.20+/-0.13 contractions/min, respectively. The mean (+/- SDev) amplitude of bladder contractions was 48.4+/-4.4 cmH(2)O. After administration of 0.01 mg/kg, 0.1mg/kg and 1mg/kg of GRC 6211, the amplitude decreased to 47.1+/-4.3, 45.6+/-5.6 and 40.2+/-4.1 cm H(2)O respectively. The effect was significant at 0.1 and 1mg/kg doses. Cystometries performed in the control group of spinalized rats showed no evidence of detrusor fatigue caused by the urethane anaesthesia and long duration of the experiment. CONCLUSION: TRPV1 antagonists may be very effective in reducing NDO of spinal origin. This finding may have profound implications for the pathogenesis and future treatment options of patients with spinal NDO. PMID- 22037501 TI - Expectancy-related changes in firing of dopamine neurons depend on orbitofrontal cortex. AB - The orbitofrontal cortex has been hypothesized to carry information regarding the value of expected rewards. Such information is essential for associative learning, which relies on comparisons between expected and obtained reward for generating instructive error signals. These error signals are thought to be conveyed by dopamine neurons. To test whether orbitofrontal cortex contributes to these error signals, we recorded from dopamine neurons in orbitofrontal-lesioned rats performing a reward learning task. Lesions caused marked changes in dopaminergic error signaling. However, the effect of lesions was not consistent with a simple loss of information regarding expected value. Instead, without orbitofrontal input, dopaminergic error signals failed to reflect internal information about the impending response that distinguished externally similar states leading to differently valued future rewards. These results are consistent with current conceptualizations of orbitofrontal cortex as supporting model-based behavior and suggest an unexpected role for this information in dopaminergic error signaling. PMID- 22037503 TI - Differential regulation of voltage-gated Ca2+ currents and metabotropic glutamate receptor activity by measles virus infection in rat cortical neurons. AB - Measles virus (MV) infection may lead to severe chronic CNS disease processes, including MV-induced encephalitis. Because the intracellular Ca(2+) concentration ([Ca(2+)](i)) is a major determinant of the (patho-)physiological state in all cells we asked whether important Ca(2+) conducting pathways are affected by MV infection in cultured cortical rat neurons. Patch-clamp measurements revealed a decrease in voltage-gated Ca(2+) currents during MV-infection, while voltage gated K(+) currents and NMDA-evoked currents were unaffected. Calcium-imaging experiments using 50mM extracellular KCl showed reduced [Ca(2+)](i) increases in MV-infected neurons, confirming a decreased activity of voltage-gated Ca(2+) channels. In contrast, the group-I metabotropic glutamate receptor (mGluR) agonist DHPG evoked changes in [Ca(2+)](i) that were increased in MV-infected cells. Our results show that MV infection conversely regulates Ca(2+) signals induced by group-I mGluRs and by voltage-gated Ca(2+) channels, suggesting that these physiological impairments may contribute to an altered function of cortical neurons during MV-induced encephalitis. PMID- 22037504 TI - Hoffmann reflex in a rat bipedal walking model. AB - The rat bipedal walking model (RBWM) refers to rats that acquired anatomical and functional characteristics for bipedal walking after the completion of a long term motor training program. We recorded the Hoffmann reflex (H-reflex) of the forelimb and hindlimb in RBWM and control (not trained, normal) rats to evaluate the effects of bipedal walking on central nervous system (CNS) activity. The H reflex recorded from the hindlimbs of the RBWM was significantly inhibited compared with that in the control. Furthermore, the inhibition of the H-reflex recorded from both forelimbs and hindlimbs by paired pulse stimulation tended to be enhanced in RBWM. These results indicate that bipedal walking or bipedal walking training cause functional changes in spinal reflex pathways in the CNS. PMID- 22037505 TI - Connexin-deficiency affects expression levels of glial glutamate transporters within the cerebrum. AB - The glial glutamate transporter subtypes, GLT-1/EAAT-2 and GLAST/EAAT-1 clear the bulk of extracellular glutamate and are severely dysregulated in various acute and chronic brain diseases. Despite the previous identification of several extracellular factors modulating glial glutamate transporter expression, our knowledge of the regulatory network controlling glial glutamate transport in health and disease still remains incomplete. In studies with cultured cortical astrocytes, we previously obtained evidence that glial glutamate transporter expression is also affected by gap junctions/connexins. To assess whether gap junctions would likewise control the in vivo expression of glial glutamate transporters, we have now assessed their expression levels in brains of conditional Cx43 knockout mice, total Cx30 knockouts, as well as Cx43/Cx30 double knockouts. We found that either knocking out Cx30, Cx43, or both increases GLT 1/EAAT-2 protein levels in the cerebral cortex to a similar extent. By contrast, GLAST/EAAT-1 protein levels maximally increased in cerebral cortices of Cx30/Cx43 double knockouts, implying that gap junctions differentially affect the expression of GLT-1/EAAT-2 and GLAST/EAAT-1. Quantitative PCR analysis further revealed that increases in glial glutamate transporter expression are brought about by transcriptional and translational/posttranslational processes. Moreover, GLT-1/EAAT-2- and GLAST/EAAT-1 protein levels remained unchanged in the hippocampi of Cx43/Cx30 double knockouts when compared to Cx43fl/fl controls, indicating brain region-specific effects of gap junctions on glial glutamate transport. Since astrocytic gap junction coupling is affected in various forms of brain injuries, our findings point to gap junctions/connexins as important regulators of glial glutamate turnover in the diseased cerebral cortex. PMID- 22037506 TI - PITX3 polymorphism is not associated with Parkinson's disease in a Chinese population. AB - Several studies have indicated that three PITX3 single nucleotide polymorphisms (SNPs), rs2281983, rs4919621 and rs3758549, are likely to be associated with Parkinson's disease (PD) in Caucasians. Some studies also suggested an age-of onset effect. We recently reported that allele and genotype frequencies did not differ between late-onset PD (LOPD) patients and controls for all three SNPs. To extend the analysis to early-onset PD (EOPD) patients, and to test whether an age of-onset effect exists in Chinese, we genotyped these SNPs in 290 Chinese EOPD patients using a ligase detection reaction (LDR). For all three SNPs, allele and genotype frequencies did not differ between total PD patients and controls, between LOPD patients and controls, between EOPD patients and controls, or between LOPD and EOPD patients. Our results suggest that these PITX3 SNPs do not contribute to the risk of developing PD in EOPD or LOPD in Chinese. PMID- 22037507 TI - Do antidepressants improve recovery from neurologic illness? PMID- 22037508 TI - Development of immunoassays for anti-electronegative LDL autoantibodies and immune complexes. AB - BACKGROUND: Electronegative low-density lipoprotein (LDL-) promotes atherosclerosis through inflammatory and immunologic mechanisms that lead to the production of anti-LDL(-) autoantibodies and to the subsequent formation of immune complexes (IC) and macrophage foam cells. We described the development and validation of an ELISA for the quantification of free anti-LDL(-) autoantibodies and an ELISA for the quantification of IC consisting of LDL(-)-bound IgG in human plasma. METHODS: LDL(-) purified from human plasma, and anti-LDL(-) monoclonal antibody Fab fragments were adsorbed onto ELISA plates to capture anti-LDL(-) autoantibodies and IC-LDL(-), respectively. The performance characteristics of both ELISAs, including the limits of detection and quantification, accuracy and inter- and intra-assay precision were evaluated. Linearity, interference and stability tests were also performed. RESULTS: The calibration range of the anti LDL(-) assay was 0.004-0.125 mU/l and plasma demonstrated a dilutional linearity when diluted 1:100, 1:200, 1:400 and 1:800. The calibration range of the IC-LDL( ) assay was 0.06-4 U/l, and plasma demonstrated a dilutional linearity when diluted 1:12.5, 1:25, 1:50 and 1:100. Both ELISAs showed intra- and inter-assay precision and recovery within the required limits for immunoassays. CONCLUSION: These ELISAs can be used in clinical studies and for the biochemical investigation of atherosclerosis. In addition, they will enable the comprehensive evaluation of the importance of bound or free autoantibodies against LDL(-) in this disease. PMID- 22037509 TI - Mutated citrullinated vimentin antibodies in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is the most common inflammatory systemic autoimmune disease, primarily affecting the peripheral joints. The past decade has been marked with revolutionary changes both in the therapeutic and diagnostic perspectives of RA. The discovery of an RA-specific citrullination-driven immune reaction gave a substantial contribution in the diagnostic approach to RA. Efforts directed towards the identification of the antigenic target specifically recognized by these autoantibodies resulted in the identification of vimentin in citrullinated form as the potential native antigen, among other proteins. Furthermore, it was found that the mutation of vimentin represents an independent trigger of antigenic properties, in addition to citrullination. As a result of this discovery, a commercial ELISA using mutated citrullinated vimentin (MCV) was developed. Increasingly, data now support the use of anti-MCV in RA diagnosis and prognosis for errosion. This review summarizes the research to date on the use of anti-MCV in RA diagnosis and prognosis and its potential use as a therapeutic marker. The pathologic role of these antibodies in RA disease is also discussed. PMID- 22037510 TI - A comparative study of serum and synovial fluid lipoprotein levels in patients with various arthritides. AB - The aim of this study was to investigate apolipoprotein (apo) A-I, apo B, lipoprotein (Lp) (a), HDL-cholesterol (C), LDL-C, triglycerides (TG) and total cholesterol (TC) values in the serum and synovial fluid (SF) of untreated rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA) patients. METHODS: Paired SF and serum samples were collected simultaneously from 14 patients with RA, 14 with PsA, and 16 with OA and tested for apo A-I, apo B, HDL-C, LDL-C, Lp(a), TC and TG. Serum C reactive protein (CRP) and amyloid A (SAA) levels were also determined. RESULTS: The inflammatory arthritis patients had higher SF lipid levels with the exception of HDL. Reflecting increased synovial permeability, the lipid SF/serum ratio was always higher in RA and PsA with respect to OA patients. The positive correlation between serum and SF apo A I, apo B, HDL-C, TG, and Lp(a) levels confirmed that there is lipoprotein diffusion into the SF. RA and PsA patients had lower concentrations of all serum lipids except for Lp(a) with respect to OA patients. The levels in the RA patients were similar to those in healthy matched controls, while the PsA patients had significantly lower apo A-I and HDL levels and higher apo B and LDL values. CONCLUSIONS: Lipid diffusion into the joint cavity, which largely depends on the degree of inflammation, may contribute to modulating local inflammatory processes. PMID- 22037511 TI - Pharmacogenetic biomarkers: cytochrome P450 3A5. AB - The immunosuppressive drugs used for solid organ transplantation all have a narrow therapeutic index with wide variation between individuals in the blood concentration achieved by a given dose. Therapeutic drug monitoring is employed routinely but may not allow optimisation of drug exposure during the critical period two to three days following transplantation. A key factor in the inter individual variability for tacrolimus, and probably sirolimus, is whether an individual is genetically predicted to express the drug metabolising enzyme cytochrome P450 3A5 (CYP3A5). Individuals predicted to express CYP3A5 by possession of at least one wild-type CYP3A5*1 allele require 1.5-2 times higher doses of tacrolimus to achieve target blood concentrations than individuals homozygous for the CYP3A5*3 allele who are functional non-expressers of CYP3A5. Planning the initial tacrolimus dose based on the CYP3A5 genotype has been shown to allow more rapid achievement of target blood concentrations after transplantation than a standard dose given to all patients. However, it remains to be demonstrated that use of this approach as an adjunct to therapeutic drug monitoring can reduce either efficacy failure (transplant rejection) or toxicity. Use of a pharmacogenetic approach to dosing sirolimus awaits testing and it is unlikely to be useful for ciclosporin or everolimus. PMID- 22037512 TI - Independent association of TG/HDL-C with urinary albumin excretion in normotensive subjects in a rural Korean population. AB - BACKGROUND: The ratio of triglycerides (TG, mg/dl) to high-density lipoprotein cholesterol (HDL-C, mg/dl) is a reliable indicator of insulin resistance and atherosclerotic diseases in some ethnic groups. This study is performed to examine the association between TG/HDL-C and albuminuria. METHODS: This cross sectional study included 9094 adult subjects (4091 men, 5003 women) who were enrolled in the Korean Genomic Rural Cohort (KGRC) and aged 40 years or more. Albuminuria was defined as a urine albumin/creatinine ratio >= 30 mg/g. Participants were categorized into TG/HDL-C quartile. RESULTS: Compared to the lowest TG/HDL-C quartile (<1.94 in men, <1.71 in women), the odds ratios (ORs) for albuminuria in participants who were categorized in the highest TG/HDL-C quartile (>= 4.98 in men, >= 4.20 in women) were 1.30 (95% CI: 0.97-1.75) and 1.36 (1.03-1.79) in men and women, respectively, when adjusted for blood pressure and other covariates. In normotensive men and women, the ORs for albuminuria in the highest TG/HDL-C quartile were 1.58 (1.04-2.39) and 1.68 (1.15-2.45), respectively, even after fully adjusted. In contrast, TG/HDL-C was not associated with albuminuria in hypertensive subjects. CONCLUSIONS: TG/HDL-C was independently associated with increased prevalence of albuminuria in normotensive rural Korean subjects aged 40 years or more in KGRC. PMID- 22037513 TI - Polyphenols activate Nrf2 in astrocytes via H2O2, semiquinones, and quinones. AB - Polyphenols, which occur both in edible plants and in foodstuff, have been reported to exert a wide range of health effects; however, the mechanism of action of these molecules is not fully understood. One important cellular pathway affected by polyphenols is the activation of the transcription factor Nrf2 via the electrophile response element, which mediates generation of phase 2 detoxifying enzymes. Our study found that Nrf2 nuclear translocation and the activity of NAD(P)H quinone oxidoreductase (NQO1) were increased significantly after treatment of astrocytes with tert-butylhydroquinone (tBHQ), resveratrol, or curcumin, at 20-50MUM. Incubation of tBHQ, resveratrol, and curcumin in the growth medium in the absence of astrocytes caused the accumulation of H(2)O(2). Treatment of cells with either glutathione or metmyoglobin was found to decrease Nrf2 translocation and NQO1 activity induced by polyphenols by up to 40 and 60%, respectively. Addition of both glutathione and metmyoglobin to growth medium decreased Nrf2 translocation and NQO1 activity by up to 100 and 80%, respectively. In conclusion, because metmyoglobin, in the presence of polyphenols and glutathione, is known to interact with H(2)O(2), semiquinones, and quinones, the up-regulation of the antioxidant defense of the cells through activation of the Nrf2 transcription factor, paradoxically, occurs via the generation of H(2)O(2) and polyphenol-oxidized species generated from the exogenous microenvironment of the cells. PMID- 22037514 TI - Inflammation-related gene expression by lipid oxidation-derived products in the progression of atherosclerosis. AB - Vascular areas of atherosclerotic development persist in a state of inflammation, and any further inflammatory stimulus in the subintimal area elicits a proatherogenic response; this alters the behavior of the artery wall cells and recruits further inflammatory cells. In association with the inflammatory response, oxidative events are also involved in the development of atherosclerotic plaques. It is now unanimously recognized that lipid oxidation derived products are key players in the initiation and progression of atherosclerotic lesions. Oxidized lipids, derived from oxidatively modified low density lipoproteins (LDLs), which accumulate in the intima, strongly modulate inflammation-related gene expression, through involvement of various signaling pathways. In addition, considerable evidence supports a proatherogenic role of a large group of potent bioactive lipids called eicosanoids, which derive from oxidation of arachidonic acid, a component of membrane phospholipids. Of note, LDL lipid oxidation products might regulate eicosanoid production, modulating the enzymatic degradation of arachidonic acid by cyclooxygenases and lipoxygenases; these enzymes might also directly contribute to LDL oxidation. This review provides a comprehensive overview of current knowledge on signal transduction pathways and inflammatory gene expression, modulated by lipid oxidation-derived products, in the progression of atherosclerosis. PMID- 22037515 TI - Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway. AB - Nitroglycerin (GTN) has been clinically used to treat angina pectoris and acute heart episodes for over 100 years. The effects of GTN have long been recognized and active research has contributed to the unraveling of numerous metabolic routes capable of converting GTN to the potent vasoactive messenger nitric oxide. Recently, the mechanism by which minute doses of GTN elicit robust pharmacological responses was revisited and eNOS activation was implicated as an important route mediating vasodilation induced by low GTN doses (1-50nM). Here, we demonstrate that at such concentrations the pharmacologic effects of nitroglycerin are largely dependent on the phosphatidylinositol 3-kinase, Akt/PKB, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signal transduction axis. Furthermore, we demonstrate that nitroglycerin dependent accumulation of 3,4,5-InsP(3), probably because of inhibition of PTEN, is important for eNOS activation, conferring a mechanistic basis for GTN pharmacological action at pharmacologically relevant doses. PMID- 22037516 TI - Inhibition of mTOR by rapamycin in the amygdala or hippocampus impairs formation and reconsolidation of inhibitory avoidance memory. AB - Mammalian target of rapamycin (mTOR), a central regulator of protein synthesis in neurons, has been implicated in synaptic plasticity and memory. Here we show that mTOR inhibition by rapamycin in the basolateral amygdala (BLA) or dorsal hippocampus (DH) impairs both formation and reconsolidation of memory for inhibitory avoidance (IA) in rats. Male Wistar rats received bilateral infusions of vehicle or rapamycin into the BLA or DH before or after IA training or retrieval. Memory retention was tested at different time points after drug infusion. Rapamycin impaired long-term IA retention when given before or immediately after training or retrieval into the BLA. When infused into the DH, rapamycin produced memory impairment when given before training or immediately after retrieval. The impairing effects of post-retrieval rapamycin required memory retrieval and were not reversed by a reminder shock. The results provide the first evidence that mTOR in the BLA and DH might play a role in IA memory reconsolidation. PMID- 22037517 TI - Prevalence and factors associated with medication compliance in Indian patients suffering from mental disorders. AB - The overall prevalence of non-adherence among patients with mental disorders in our study was 38%. However, 50% of the non-adherents were suffering from schizophrenia. Younger patients with good social support had good adherence whereas those with more severe illnesses and who were sedated were associated with non-adherence. PMID- 22037518 TI - Plea for greater use of spinal anaesthesia in developing countries. AB - When it is indicated for surgical procedures below the umbilicus in our low resource countries, spinal anaesthesia has many advantages: it is simple, cheap, safe and easy to learn and carry out. It reduces nursing load and the risk of aspiration pneumonitis as well as overall postoperative mortality and morbidity. We prospectively carried out a study of 419 patients operated under spinal anaesthesia during our normal surgical activities. Despite the materials and conditions that were not always those recommended in the published literature, we had very satisfactory results with: (1) a high patient acceptance rate (93.9%); (2) relatively rare adverse effects - the most frequent being hypotension and vomiting each observed in seven (1.67%) patients. We had two cases (0.48%) of the rare cauda equina syndrome. In poor-resource countries, the culture of spinal anaesthesia should be better developed and encouraged by the training institutions. PMID- 22037519 TI - The 'hit by a stick' disease: an epidemiologic study of the causes of trauma in a non-profit hospital in rural Ethiopia. AB - Traumatic injuries are one of the leading causes of death and disability worldwide and represent a very important public health problem in countries like Ethiopia, where there are insufficient centres of trauma care and where an interest in prevention has only relatively recently been awakened. The aim of this study was to investigate the causes of trauma at St Luke Catholic Hospital. We conducted a one-year retrospective study on 2969 patients who suffered from trauma. Every traumatized patient was classified by age, sex, cause and site of the trauma. The admission rate and hospital stays were also analysed. The most common causes of injury were: interpersonal conflict (32.2%); falling (15.1%); and road traffic incidents (RTIs; 14%). Men (71.7%) and young adults (37.6%; range 15-29 years) were the most affected, while head and neck were the most affected sites (33%). Half of the 377 admitted patients stay in hospital for more than a week. The 'hit by a stick' disease can be reduced with appropriate public health campaigns on trauma prevention. This is a priority in trauma prevention, especially in the rural areas. PMID- 22037520 TI - Palatal ulceration as the first sign of pulmonary tuberculosis: a case report. AB - Tuberculosis (TB) is one of the leading casues of morbidity and death in a number of countries worldwide. A healthy 42-year-old patient presented with a chronic palatal ulcer that was not responsive to routine antibiotic treatment. A biopsy and further systemic investigation revealed a diagnosis of TB. An eight-month extended course of oral rifampin and isoniazid was instituted successfully resulting in complete resolution of symptoms. It is important that clinicians be aware that chronic oral ulcerations may be the first sign of systemic disease. A biopsy should therefore be mandatory for any chronic oral ulcer not responsive to conventional treatment. PMID- 22037521 TI - Synthesis of diaryl ketones via a phosphine-free Fukuyama reaction. AB - The synthesis of unsymmetrical diaryl ketones via the Fukuyama coupling of thioesters and organozinc reagents is described. Typically, the synthesis of diaryl ketones using this methodology provides low yields. The simple complex, Pd(dba)(2), was found to convert a variety of aryl thioesters to diaryl ketones in good yields. PMID- 22037522 TI - Body appearance and quality of life in adult patients with adolescent idiopathic scoliosis treated with a brace or under observation alone during adolescence. AB - STUDY DESIGN: The Scoliosis Research Society (SRS) brace study (published in the JBJS-A, 1995) was comprised of patients with adolescent idiopathic scoliosis with moderate curve sizes (25 degrees -35 degrees ). Forty observed and 37 braced patients (77% of the original group) attended a follow-up, a mean of 16 years after onset of maturity. OBJECTIVE: To analyze whether the subjectively evaluated present body appearance affects outcome as measured by quality of life in adult patients, previously treated by observation alone (nonbraced) or with a brace during adolescence. SUMMARY OF BACKGROUND DATA: Few reports exist where validated outcome measures for body appearance have been used. METHODS: Two quality-of-life questionnaires, the Scoliosis Research Society-22 (SRS-22) questionnaire and the 36-Item Short-Form Survey Instrument (SF-36), were answered. The patient's opinion on body appearance was evaluated pictorially (i.e., sketches) using the spinal appearance questionnaire, in which 7 aspects of asymmetry are graded. These scores were compared with curve sizes, scoliometer measurements for grading trunk asymmetry, and quality-of-life measures. RESULTS: At follow-up, both groups were similar in terms of age (mean = 32 years) and curve size (mean = 35 degrees ). Distortion was inversely related to SRS-22 total score and satisfaction/dissatisfaction with management subscore, but not related to the SRS 22 function subscore. No difference was found between the groups in terms of trunk rotation, where the means were 10.7 degrees and 10.8 degrees for the nonbraced and braced patients, respectively. The nonbraced patients estimated that their body appearance was significantly less distorted than the braced patients (mean = 12.9 and 15.0, respectively; P = 0.0028). CONCLUSION: Patients who experienced less body asymmetry were more satisfied with treatment and had a better quality of life. In spite of similar curve sizes and trunk rotation in both groups, the nonbraced patients felt that their body appearance was less distorted than that of the braced patients. PMID- 22037523 TI - Development of a French-Canadian version of the Oswestry Disability Index: cross cultural adaptation and validation. AB - STUDY DESIGN: Cross-cultural translation and psychometric testing. OBJECTIVE: To translate, culturally adapt, and validate the Oswestry Disability Index (ODI) version 2.0 for the French-Canadian population. SUMMARY OF BACKGROUND DATA: Many authors have recommended the administration of standardized instruments, rather than the creation of new scales, and advocate the adaptation of validated questionnaires in other languages. The application of these scales in different countries and by cultural groups necessitates cross-cultural adaptation. Many scales evaluate the functional incapacity resulting from low back pain. The ODI is among the most commonly used for this purpose. METHODS: The French-Canadian ODI (ODI-FC) was developed by cross-cultural adaptation following internationally recommended methodology: forward translation, back translation, expert committee revision, and clinical evaluation of the prefinal version. Psychometric testing was performed on 72 patients with chronic low back pain. The subjects were recruited from a physiatry department in a university hospital and from a private practice physiatry clinic. They came from the Montreal area. The psychometric testing included internal consistency (Cronbach alpha), test-retest reliability (intraclass correlation coefficient) with a time interval set at 48 hours, and construct validity, comparing the ODI-FC with the Roland-Morris Disability Questionnaire and the Quebec Back Pain Disability Scale (Pearson correlation coefficient). RESULTS: In 44.4% of the subjects, the average duration of low-back pain varied between 1 and 5 years. Average score for the ODI-FC was 29.2. Good internal consistency was found (Cronbach alpha = 0.88). Reliability was excellent, with intraclass correlation coefficient = 0.92 (95% confidence interval, 0.87-0.95). Construct validity results revealed excellent correlations between the ODI and the Quebec Back Pain Disability Scale (r = 0.90) and between the ODI and the Roland-Morris Disability Questionnaire (r = 0.84). CONCLUSION: Cross-cultural translation and adaptation of the ODI-FC were successful. Psychometric testing determined that the instrument was homogeneous, reliable, and valid. It could be employed in future clinical trials in Canada and possibly in other French-speaking countries. PMID- 22037524 TI - The Dysphagia Short Questionnaire: an instrument for evaluation of dysphagia: a validation study with 12 months' follow-up after anterior cervical spine surgery. AB - STUDY DESIGN: Prospective clinical validation study of questionnaire to assess dysphagia. OBJECTIVE: To test validity and reliability of Dysphagia Short Questionnaire (DSQ), and also to determine levels of dysphagia over time after anterior cervical spine surgery (ACSS). SUMMARY OF BACKGROUND DATA: Dysphagia is common after ACSS but reports on the incidence vary widely between 1% and 79%, indicating an evaluation problem. Several tools for evaluation of dysphagia exist but common features are that they are cumbersome to use and usually are designed for patients with neurological or malignant diseases in the neck region. Others are not validated, for example, the Bazaz score. There is, thus, a need for a more adapted tool to evaluate dysphagia in patients undergoing ACSS. METHODS: The DSQ was constructed in collaboration with a group of ear-nose-and-throat specialists. In a first validation study, 45 patients with stationary dysphagia for various reasons completed the DSQ twice 2 weeks apart, the M.D. Anderson Dysphagia Inventory (MDADI), the Bazaz score, and a quality-of-life score, the EQ 5D. To evaluate the utility of the DSQ, a second validation study was performed, where 111 subjects undergoing ACSS for degenerative disk disease completed the form preoperatively and at 4 weeks, 3 months, and 1 year after surgery. RESULTS: In the first study, the DSQ correlated to MDADI (r = 0.59) and showed good reproducibility. The Bazaz score did not correlate to the DSQ, the MDADI, or the EQ-5 D. In the second study, dysphagia was present in a few patients already preoperatively. At 4 weeks, 85% of the patients reported dysphagia. The level had dropped significantly at 3 months and had returned to baseline levels at 1 year. CONCLUSION: We consider the DSQ to be a validated tool for the assessment of dysphagia in ACSS patients. Dysphagia after ACSS for cervical spondylosis is common but the symptoms on a group level are not very severe and are also temporary. PMID- 22037525 TI - Primary pyogenic infection of the spine in intravenous drug users: a prospective observational study. AB - STUDY DESIGN: A prospective comparative analysis of surgically-treated nontuberculous primary pyogenic infection of the spine (PPIS). OBJECTIVE: To evaluate and compare the demographics, presentation, treatment and outcomes of surgically-treated PPIS between intravenous drug users (IVDU) and non-IVDU patients. SUMMARY OF BACKGROUND DATA: This is the first prospective cohort comparative analysis of the clinical outcomes of surgically-treated PPIS between IVDU and non-IVDU populations. This is also the largest cohort of consecutive surgically-treated PPIS in a population of IVDU. METHODS: Data on all patients with PPIS presenting to a quaternary referral center during a 4-year period from 2004 were collected in a prospectively maintained customized database. RESULTS: During the study period there were 102 patients treated for PPIS of which 51 were IVDU. Of this IVDU group, the mean age was 43 years (range: 25-57). Twenty-three had human immunodeficiency virus, 43 had hepatitis C, and 13 had hepatitis B. All were using cocaine, 26 were also using heroin and 44 were using at least 3 recreational drugs. Thirty patients presented with axial pain of a mean duration of 51 days (range: 3-120 days). Of the IVDU patients with neurological deficit on presentation, the mean American Spinal Injury Association (ASIA) motor score was 58.6. The most common ASIA motor levels involved were C4 and C5. Mean duration of neurological symptoms was 7 days (range: 1-60 days). Twenty-six were already receiving i.v. antibiotics for known spinal infection and 33 patients had an identifiable organism on blood cultures (19 methicillin-sensitive Staphylococcus aureus, 9 methicillin-resistant S. aureus). Forty-four of the 51 IVDU patients were treated surgically. Thirty-four of the 44 surgically treated cases involved the cervical spine. Twenty-two had a posterior approach alone, 13 had anterior only while 9 required combined anterior and posterior approaches at the index surgery. Seven required early revision for hardware failure (none of whom has combined approach) and 2 developed a postoperative surgical site infection (SSI). Thirty-seven of the 51 IVDU patients were apprehended at least once using illicit drugs while in hospital. Mean duration of antibiotic treatment after surgery was 62 days. At discharge, 28 of 44 patients had neurological improvement (mean = 20 ASIA points, range: 1-55), 11 had neurological deterioration during treatment (mean = 13, range = 1-50), and 5 were unchanged. Among the IVDUs there were no in hospital deaths. At 2 years after index admission 13 IVDU patients were dead, and none were attending for follow-up despite all efforts to locate the patients. In the non-IVDU group, the mean age of the 51 patients was 56 years (range 25-83). Thirty-four patients presented with axial pain with a mean duration of 105 days (range 2-365). Mean ASIA motor score of patients with neurological deficit on admission was 74. Most common ASIA level was T12. Mean duration of neurological symptoms was 12 days (range 1-84). Thirteen patients were receiving i.v. antibiotics for known spinal infection and 20 patients had an identifiable organism on blood culture (30% methicillin-sensitive S. aureus, 50% methicillin resistant S. aureus). Forty-four of these 51 non-IVDU patients were treated surgically. Thirty-five of the 44 surgically-treated cases involved the thoracic or lumbar spines. Twenty-nine had a posterior approach alone, 3 had anterior alone while 12 required combined approaches. No early hardware failures were seen in the non-IVDU group while 4 developed SSI. Mean duration of antibiotic treatment after surgery was 45 days. At discharge 21 patients had neurological improvement (mean 9 ASIA points, range: 1-17). Five had neurologic deterioration with a mean motor loss of 16 points (10-23). There were 4 in-hospital deaths among the non-IVDU group. At 2 years after index admission, 19 patients were dead and the remainder were all available for follow-up. CONCLUSION: There are significant differences in demographics, presentation, treatment and outcomes of primary spinal pyogenic infection between a population of IVDU and a comparable cohort of non-IVDU. The IVDU group presents with cervical quadriplegia while it is the thoracolumbar spine that is almost exclusively involved in the non-IVDU group. Among the IVDUs, surgical management is complex with a high incidence of early hardware failure. SSI is significantly more common among non-IVDU. Significant neurological improvement can be expected in the majority of IVDU patients with a high mortality rate among the non-IVDU. IVDU are unreliable patients and in-hospital, in-halo incarceration is recommended where possible. PMID- 22037526 TI - Morbid obesity increases cost and complication rates in spinal arthrodesis. AB - STUDY DESIGN: A retrospective cross-sectional study of all spinal fusions in California from 2003 to 2007. OBJECTIVE: This study analyzes whether morbid obesity alters rates of complications and charges in patients undergoing spinal fusion. SUMMARY OF BACKGROUND DATA: Prior studies of obesity have focused on lumbar fusion; some identified increases in wound complications. However, these studies typically do not account for comorbidities, do not examine nonlumbar fusions, and usually are small single institution series. METHODS: Our study used the Healthcare Cost and Utilization Project's California State Inpatient Databases (CA-SID) to identify normal weight and morbidly obese patients admitted in California between 2003 and 2007 for 4 types of spinal fusion: anterior cervical fusion (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] procedure code 810.2), posterior cervical fusion (810.3), anterior lumbar fusion (810.6), and posterior lumbar fusion (810.8). Demographic, comorbidity, and complications data were collected. Primary outcome was in-hospital complication; secondary outcomes were total cost, length of stay, and in-hospital mortality. Multivariate logistic regression was performed. RESULTS: In total 84,607 admissions were identified, of which 1455 were morbidly obese. Morbid obesity was associated with 97% higher in-hospital complication rates (13.6% vs. 6.9%), sustained across nearly all complication types (cardiac, renal, pulmonary, wound complications, among others). Mortality among the morbidly obese was slightly higher (0.41 vs. 0.13, P < 0.01) as were average hospital costs ($108,604 vs. $84,861, P < 0.0001). Length of stay was longer as well (4.8 d vs. 3.5 d, P < 0.0001). All effects were less pronounced in posterior cervical fusions. On multivariate analysis, morbid obesity was the most significant predictor of complications in the anterior cervical and posterior lumbar fusion groups (more than age, demography, and other comorbidity). CONCLUSION: Morbid obesity seems to increase the risk of multiple complication types in spinal fusion surgery, most particularly in anterior cervical and posterior lumbar approaches. PMID- 22037527 TI - Use and outcomes of wound drain in spinal fusion for adolescent idiopathic scoliosis. AB - STUDY DESIGN: A multicenter retrospective analysis. OBJECTIVE: To evaluate outcomes of closed-suction wound drainage after posterior spinal fusion with instrumentation for adolescent idiopathic scoliosis and to identify surgeon patterns of drain use in this cohort. SUMMARY OF BACKGROUND DATA: There is little evidence on the use of drains in spinal surgery, particularly for repair of adolescent idiopathic scoliosis. Studies on hip and knee arthroplasty suggest no advantage to draining. There are few published reports on surgeon technique and rationale for drain use in spinal surgery. METHODS: Patients were divided into drain and no drain cohorts and followed for 2 years. Primary outcome was complication rate. A separate survey was conducted from surgeons in the Spinal Deformity Study Group to evaluate drain practice patterns. RESULTS: There were 324 drained and 176 undrained patients. Complication rate did not differ between the drain and no drain cohorts in any of the 4 categories (wound infection, neural injury, other infection, and other complication) at any time (all P > 0.1). More drained patients received postoperative transfusions compared with those without a drain (43% vs. 22%, P < 0.001). Of the 50 surgeons in the group, 36 used drains. Half of these did so out of habit. Surgeons tended to place deep drains with bulb suction, without drain manipulation. Half removed drains on the basis of output, whereas half removed them after 1 to 3 days. CONCLUSION: More patients tended to receive wound drains than not receive wound drains. Drains did not impact complication rate and drained patients received more blood product. There are no universal criteria for draining and practice patterns vary widely. PMID- 22037528 TI - Retrospective computed tomography scan analysis of percutaneously inserted pedicle screws for posterior transpedicular stabilization of the thoracic and lumbar spine: accuracy and complication rates. AB - STUDY DESIGN: Retrospective clinical data analysis. OBJECTIVE: To investigate the misplacement rate and related clinical complications of percutaneous pedicle screw insertion in the thoracic and lumbar spine. SUMMARY OF BACKGROUND DATA: Percutaneous insertion of cannulated pedicle screws has been developed as a minimally invasive alternative to the open technique during instrumented fusion procedures of the thoraco-lumbar spine. The reported rate of screw misplacement using open techniques is well described, however data is lacking on the exact failure rate of the percutaneous technique. METHODS: A total of 424 percutaneously inserted pedicle screws from 2007 to 2010 were analyzed in 88 patients, from a single surgeon series (RJM). Axial reformatted computer tomographic images were examined by 2 independent observers and individual and consensus interpretation was obtained for each screw position. A simple grading system was used for assessment of screw accuracy--Grade 0: screw within cortex of pedicle; Grade 1: screw thread breach of wall of pedicle <2 mm; Grade 2: significant breach >2 mm with no neurological compromise; Grade 3: complication including pedicle fracture, anterior breach with neuro-vascular compromise, and lateral or medial breach with neurological sequelae. RESULTS: The indications for percutaneous pedicle screw insertion include: degenerative (78%), trauma (13%), tumour (8%), and infection (1%). Pedicle screws were inserted into level T4 to S1. The most common levels performed include L4 and L5 with the most common indication for surgery being an L4/5 spondylolisthesis. 383 out of 424 screws (90.3%) were placed in the cortical shell of the pedicle (Grade 0). Forty-one screws (9.7%) were misplaced from T4 to S1. Of these, the majority were Grade 1 pedicle violations (24 screws; 5.7%), with 15 Grade 2 violations (3.5%) and 2 Grade 3 violations (0.5%). Of the 2 Grade 3 pedicle violations, both were pedicle fractures but only 1 had associated neurological deficit (L4 radiculopathy postoperatively). CONCLUSION: Percutaneous insertion of cannulated pedicle screws in the thoracic and lumbar spine is an acceptable technique with a low complication rate in experienced hands. The overall rate of perforation is below the higher rates reported in the literature for the open technique. Complication rates including pedicle fracture were low. PMID- 22037529 TI - Tissue engineering of the intervertebral disc with cultured nucleus pulposus cells using atelocollagen scaffold and growth factors. AB - STUDY DESIGN: In vitro experiment using rabbit nucleus pulposus (NP) cells seeded in atelocollagen scaffolds under the stimulation of growth factors. OBJECTIVE: To demonstrate the effect of anabolic growth factors in rabbit NP cells cultured in atelocollagen type I and type II. SUMMARY OF BACKGROUND DATA: Atelocollagen provides intervertebral disc (IVD) cells for a biocompatible environment to produce extracellular matrix. IVD cells with exogenous transforming growth factor beta 1 (TGF-beta1) and bone morphogenetic protein-2 (BMP-2) also render an increase in matrix synthesis. However, the effect of anabolic growth factors in NP cells cultured in atelocollagens was not elucidated before. METHODS: Rabbit NP cell was harvested, enzymatically digested, and cultured. The NP cells were seeded to atelocollagen type I and type II scaffolds, and then cultures were exposed to TGF-beta1 (10 ng/mL) and/or BMP-2 (100 ng/mL). DNA synthesis was measured using [4H]-thymidine incorporation. Newly synthesized proteoglycan was measured using [35S]-sulfate incorporation. Reverse transcription-polymerase chain reactions (RT-PCRs) for mRNA expression of aggrecan, collagen type I, collagen type II, and osteocalcin were performed. RESULTS: Rabbit NP cells cultured in atelocollagen type I scaffold showed an increase (1.7 to 2.4-fold) in DNA synthesis in response to TGF-beta1 and/or BMP-2 (P < 0.05), whereas NP cultures in atelocollagen type II demonstrated a 30% increase in DNA synthesis only with combination of both growth factors compared with control (P < 0.05). Rabbit NP cells in atelocollagen type II scaffold with TGF-beta1 and combination of both growth factors exhibited robust 5.3- and 5.4-fold increases in proteoglycan synthesis (P < 0.05), whereas any cultures in atelocollagen type I failed to show any significant increase compared with control. Rabbit NP cells in atelocollagen type I and type II scaffolds with TGF-beta1 and/or BMP-2 demonstrated the upregulation of aggrecan, collagen type I, and collagen type II mRNA expression compared with saline control (P < 0.05). The response in transcriptional level was more robust in atelocollagen type II than in type I. In any event, there is no recognizable expression of osteocalcin (P < 0.05). CONCLUSION: NP cells in atelocollagens under the stimulation of TGF-beta1 and BMP 2 exhibited anabolic responses in transcriptional and translational levels. Hence, such an approach can provide a suitable engineered tissue for IVD regeneration with potential for robust refurbishment of matrix. PMID- 22037530 TI - The effect of anterior-posterior shear on the wear of CHARITE total disc replacement. AB - STUDY DESIGN: An in vitro study of the wear rates of the CHARITE lumbar total disc replacement (TDR). OBJECTIVE: To investigate the effect of anterior posterior shear on the in vitro wear rates of the CHARITE lumbar TDR. SUMMARY OF BACKGROUND DATA: Current standards prescribe only 4-degrees of freedom (DOF) inputs for evaluating the in vitro wear of TDRs, despite the functional spinal unit incorporating 6 DOF. Anterior-posterior shear has been highlighted as a significant load, particularly in the lumbar spine. A previous study investigated the effect of an anterior-posterior shear on the ProDisc-L, finding that wear rates were not significantly different from 4-DOF wear tests. METHODS: Six CHARITE lumbar discs were mounted in a 5 active DOF spine wear simulator and tested under 4-DOF (ISO18192) conditions. Six further CHARITE lumbar discs were tested under 5-DOF conditions, consisting of 4-DOF conditions plus an anterior posterior shear displacement of +2/-1.5 mm. The displacement was decreased and then increased by a factor of 2 to investigate the effect of the magnitude of displacement. Micro-computed tomographic scans of the discs were taken before and after wear testing, and the height loss of the discs was calculated. These were compared with the same measurements taken from explanted CHARITE discs, micro computed tomography scanned at another institution. RESULTS: Wear rates for 4 DOF (12.2 +/- 1.0 mg/MC) were not significantly different from 4-DOF tests on the ProDisc-L. Wear rates were significantly increased (P < 0.01) for "standard" 5 DOF conditions (22.3 +/- 2.0 mg/MC), decreased 5 DOF (24.3 +/- 4.9 mg/MC), and increased 5 DOF (29.1 +/- 7.6 mg/MC). The height loss of the explants and in vitro tested discs were not significantly different (P > 0.05). CONCLUSION: The addition of anterior-posterior shear to wear testing inputs of the CHARITE lumbar TDR increases the wear rate significantly, which is in direct contrast to the previous 5-DOF testing on the ProDisc. This study highlights the importance of clinically relevant testing regimens, and that test inputs may be different for dissimilar design philosophies. PMID- 22037531 TI - Unanticipated revision surgery in adolescent idiopathic scoliosis. AB - STUDY DESIGN: Retrospective case series. OBJECTIVE: The objective of this study was to share our experience in the surgical treatment of adolescent idiopathic scoliosis (AIS), specifically the rate of revision surgeries and their indications. SUMMARY OF BACKGROUND DATA: Minimizing AIS surgical morbidity includes prevention of short- and long-term complications that could require an unanticipated revision. There have been an increasing number of reports about revision rates and their causes in AIS. This study summarizes the experience of a large patient population treated by a single surgeon in a single institution. METHODS: All patients who underwent surgical treatment for AIS between 10 and 20 years of age during 1983 to 2005 were reviewed. All revision surgeries performed during the same period were searched. The indications for revision and type of procedure performed were recorded. RESULTS: A total of 502 patients with AIS underwent spinal fusion with instrumentation at an average age of 14.3 years at initial surgery. In 485 patients, the surgery consisted of posterior-only spinal fusion. A total of 24 revision surgeries were performed for 23 patients (4.9%; cumulative probability of revision = 8%). The primary indications for revision were residual rib deformity (n = 8), instrumentation dislodgement (n = 4), compensatory curve progression (n = 3), junctional kyphosis (n = 3), and symptomatic implants (n = 3). One patient had a late infection. There was 1 case of pseudoarthrosis. One patient requested scar revision. There were no cases of neurological deficit. CONCLUSION: In this single-surgeon series, revision after the index spinal fusion was required for a relatively low proportion of patients. The main indications for revision were residual rib deformity, hook dislodgment, and progression of the unfused compensatory curve. PMID- 22037532 TI - Are antifibrinolytics helpful in decreasing blood loss and transfusions during spinal fusion surgery in children with cerebral palsy scoliosis? AB - STUDY DESIGN: Therapeutic comparative study. OBJECTIVE: To evaluate the safety and efficacy of antifibrinolytic (AF) agents in reducing blood loss and transfusions during posterior spinal fusion (PSF) in children with cerebral palsy (CP) scoliosis. SUMMARY OF BACKGROUND DATA: Scoliosis surgery in CP children is associated with substantial blood loss. Few reports on the role of AFs exist. METHODS: A multicenter, retrospective review of a prospectively collected database of 84 consecutively enrolled patients with CF (age < 18 years) with spinal deformity who underwent PSF and instrumentation. The use of AFs, tranexamic acid (TXA), epsilon-aminocaproic acid (EACA), or none was based on the surgeon preference. Estimated blood loss (EBL), transfusion requirements, and length of stay were recorded. Analysis was performed with the independent-samples t test and 1-way analysis of variance with post hoc Bonferroni analysis. RESULTS: The average age at the time of surgery was 14.4 +/- 2.6 years. The groups were well matched in preoperative major deformity, age, levels fused, and operating time. Forty-four patients received AFs (30 TXA and 14 EACA), and 40 received no antifibrinolytics (NAF). The EBL averaged 1684 mL for the AFs group and 2685 mL for the NAF group (P = 0.002). There was more cell salvage transfusion in the NAF group. No significant differences were found in total transfusion requirements. There was a trend for decreased hospital stay in the AFs group. No adverse effects were seen. On comparison of the 3 groups (NAF, TXA, and EACA), a significant difference was observed between the TXA and the other groups with respect to EBL and cell salvage transfusion. CONCLUSION: AFs significantly reduced intraoperative EBL associated with PSF, with no adverse effects; however, we could not demonstrate significant differences in total transfusion, except in cell salvage. TXA was more effective than EACA in decreasing the EBL and cell salvage transfusion. PMID- 22037533 TI - Chondrosarcoma of the mobile spine: a review of 21 cases treated at a single center. AB - STUDY DESIGN: Retrospective case series. OBJECTIVE: To determine the effect of modern surgical and aggressive radiation techniques on outcome in patients with spinal chondrosarcoma. SUMMARY OF BACKGROUND DATA: Chondrosarcoma of the spine presents a difficult surgical challenge. Surgical excision is considered the standard of care, yet complete excision is not always feasible, and rates of local control and survival are inferior to those reported for the extremities. METHODS: We performed a retrospective review of cases of chondrosarcoma involving the spine above the sacrum treated surgically at our institution between 1984 and 2006. Medical charts, radiology reports, pathology reports, and operative notes were reviewed for all patients. Available imaging studies were also reviewed. The Student t test and Fisher exact test were used to compare baseline differences between groups. Survivorship analysis was performed using Kaplan-Meier methodology. Overall survival was calculated on the basis of en bloc resection, margins, local recurrence, and metastasis. RESULTS: Twenty-one patients were treated surgically for chondrosarcoma of the mobile spine. Twenty of the 21 patients were also treated with radiation with a mean dose of 71 Gy (range, 53 83). The average overall survival for all patients in our series was 120.5 months (SE = 32.9; range, 8.5-298.9 months). The 1- and 5-year survival rates for all patients were 90% and 61%, respectively. Patients treated with en bloc resection had a better overall survival (198 months: SE = 24.5; range, 24-224.7 months) than those who underwent intralesional excision (77 months: SE = 27.3; range, 8.5 298.9 months) (P = 0.05). Five (24%) patients developed local recurrence and 9 (43%) developed metastasis. All recurrences occurred in patients who underwent intralesional resection. Metastasis, high-grade tumor, and positive surgical margins were associated with worse overall survival (P < 0.001, 0.02, and 0.04, respectively). CONCLUSION: In this series, en bloc resection, the absence of metastasis, low-grade tumors, and negative margins were associated with improved overall survival. The aggressive use of sophisticated surgical and radiation techniques appears to confer an advantage to patients, decreasing local recurrence and increasing overall survival, even following incomplete surgical resection. PMID- 22037534 TI - Long-term clinical outcomes of surgery for adolescent idiopathic scoliosis 21 to 41 years later. AB - STUDY DESIGN: A case control study. OBJECTIVE: To determine the clinical outcome of middle-aged patients surgically treated for adolescent idiopathic scoliosis and to compare their outcomes with assessments of age- and sex-matched healthy controls. SUMMARY OF BACKGROUND DATA: Several long-term follow-up studies have been published on the clinical outcomes of surgical treatment for adolescent idiopathic scoliosis in patients who have reached their 20s or 30s. However, clinical outcomes in patients who have reached middle age remain unknown. METHODS: This study included 256 patients surgically treated for adolescent idiopathic scoliosis (AIS) between 1968 and 1988. The Scoliosis Research Society Patient Questionnaire (SRS-22) and Roland-Morris Disability Questionnaire (RDQ) were used for evaluating long-term clinical outcomes. Sixty-six (25.8%; 62 females, 4 males; mean age, 46.0 years [range 34-56]) of the 256 patients responded to the questionnaires. The mean follow-up period was 31.5 (range 21-41) years. Seventy-six healthy age- and sex-matched individuals with neither a history of spinal surgery nor scoliosis were selected as a control (CTR) group. RESULTS: On the basis of the SRS-22 responses, AIS patients had significantly decreased function (AIS: 4.3 +/- 0.6, CTR: 4.7 +/- 0.5, P < 0.01) and decreased self-image (AIS: 3.0 +/- 0.8, CTR: 3.7 +/- 0.5, P < 0.01) in comparison with the controls, but the 2 groups were similar with respect to pain (AIS: 4.3 +/- 0.6, CTR: 4.2 +/- 0.5, P = 0.14) and mental health (AIS: 3.9 +/- 0.9, CTR: 3.7 +/- 0.7, P = 0.14). The RDQ responses indicated that low back pain was not significantly increased in the AIS group compared with the CTR group (AIS: 1.8 +/ 3.5, CTR: 1.4 +/- 3.1, P = 0.36). CONCLUSION: Surgery had no demonstrable adverse effects on pain or mental health in these middle-aged AIS patients 21-41 years after surgery, although the AIS patients did have significantly lower function and lower self-image than the controls. PMID- 22037535 TI - A meta-analysis of comparative outcomes following cervical arthroplasty or anterior cervical fusion: results from 4 prospective multicenter randomized clinical trials and up to 1226 patients. AB - STUDY DESIGN: Meta-analysis of 4 prospective randomized controlled Food and Drug Administration (FDA) Investigational Device Exemption (IDE) clinical trials. OBJECTIVE: To maximize the information available from 4 IDE studies by analyzing the combined outcomes of cervical arthroplasty versus fusion at 24-month follow up. SUMMARY OF BACKGROUND DATA: To date, 4 randomized clinical trials have been completed in the United States under FDA IDE protocols to study cervical arthroplasty. Each trial reported arthroplasty to be at least as successful as fusion controls based on noninferiority trial designs. However, sample sizes in any given trial may not be sufficient to demonstrate superiority of treatment effect. Meta-analysis enables pooling of results from comparable trials, which may lead to more precise and statistically significant estimates of treatment effect. METHODS: Four cervical arthroplasty randomized clinical trials with comparable enrollment criteria and outcome measures were conducted independently by 3 separate sponsors to study the following devices: Bryan, Prestige, ProDisc C, and PCM cervical disc replacements. A total of 1608 patients were treated across 98 investigative sites. Data were available for 1352 treated patients, of which 1226 were evaluable at 24 months. Assessments included clinical success definitions based on neck disability index, maintenance or improvement of neurological status, subsequent surgery or intervention at the index level (survivorship), and a composite score comprising these as well as serious device related adverse events. Trial endpoint comparisons were made at 24 months postoperatively. For each endpoint, a random-effects meta-analysis was performed to compare the success rates of cervical arthroplasty with anterior cervical discectomy and fusion (ACDF). Also, supportive frequentist and bayesian analyses were performed. RESULTS: The pooled primary overall success results indicated a statistically significant treatment effect favoring arthroplasty compared with ACDF. Overall success was achieved by 77.6% of the arthroplasty patients and by 70.8% of the ACDF patients (pooled odds ratio [OR]: 0.699, 95% confidence interval [CI]: 0.539-0.908, P = 0.007). The results of the individual subcomponent meta-analyses, all of which favored arthroplasty, were neck disability index success (OR: 0.786, 95% CI: 0.589-1.050, P = 0.103), neurological status (OR: 0.552, 95% CI: 0.364-0.835, P = 0.005), and survivorship (OR: 0.510, 95% CI: 0.275-0.946, P = 0.033). Only the survivorship endpoint suggested low heterogeneity. CONCLUSION: These findings suggest that cervical arthroplasty is superior to ACDF in overall success, neurological success, and survivorship outcomes at 24 months postoperatively. PMID- 22037536 TI - Magnetic properties of multiferroics-semiconductors Eu(1-x)Ce(x)Mn2O5. AB - Studies of magnetization, magnetoresistance, and magnetic oscillations in semiconductor-multiferroics Eu(1-x)Ce(x)Mn2O5 (x = 0.2-0.25) (ECMO) at temperatures ranging from 5 to 350 K in magnetic fields up to 6 T are presented. It is shown that phase separation and charge carrier self-organization in the crystals give rise to a layered superstructure perpendicular to the c axis. An effect of magnetic field cycling on the superstructure, magnetization, and magnetoresistance is demonstrated. X-ray diffraction studies of ECMO demonstrating the effect of magnetic field on the superstructure are presented. The de Haas-van Alphen magnetization oscillations in high magnetic fields and the temperature-induced magnetic oscillations in a fixed magnetic field are observed at low temperatures. Below 10 K the quantum corrections to magnetization due to the weak charge carrier localization in 2D superlattice layers occur. It is shown that at all the temperatures the Eu(1-x)Ce(x)Mn2O5 magnetic state is dictated by superparamagnetism of isolated ferromagnetic domains. PMID- 22037537 TI - Universal prevention is associated with lower prevalence of fetal alcohol spectrum disorders in Northern Cape, South Africa: a multicentre before-after study. AB - AIMS: Prevalence of fetal alcohol spectrum disorders (FASDs) is remarkably high in several provinces of South Africa; yet population-level knowledge of the harms of maternal drinking remains low. In two heavily affected areas, we assessed effectiveness of interventions to heighten awareness of these harms and to alter social norms about drinking in pregnancy. METHODS: FASD prevalence, maternal knowledge and drinking behaviours were investigated in two Northern Cape Province towns, before and after interventions which included highlighting FASD using local media and health promotion talks at health facilities. Independently, two dysmorphologists and a neuropsychometrist examined children at 9 and 18 months. RESULTS: Pre-intervention maternal knowledge of alcohol harms was low and FASD prevalence 8.9% (72/809). Interventions reached high coverage and knowledge levels increased substantially. FASD prevalence was 5.7% post-intervention (43/751; P = 0.02); 0.73 lower odds, controlling for maternal age and ethnicity (95% confidence interval = 0.58-0.90). No change was detected in more severe FASD forms, but in the whole population, median dysmorphology scores reduced from 4 [inter-quartile range (IQR) = 2-7] to 3 (IQR = 1-6; P = 0.002). CONCLUSION: This, the first prevention study using FASD outcomes, suggests that universal prevention might reduce FASD by ~30% and have population-level effects. This supports intensifying universal interventions where knowledge of harms of maternal drinking is low. These efforts need to be accompanied by alcohol dependence treatment to lower more severe FASD forms. PMID- 22037538 TI - Regulation of coronary resistance vessel tone in response to exercise. AB - Exercise is a primary stimulus for increased myocardial oxygen demand. The ~6 fold increase in oxygen demand of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen extraction (which is already ~70% at rest) increase only modestly in most species. As a result, coronary blood flow is tightly coupled to myocardial oxygen consumption over a wide range of physical activity. This tight coupling has been proposed to depend on periarteriolar oxygen tension, signals released from cardiomyocytes and the endothelium as well as neurohumoral influences, but the contribution of each of these regulatory pathways, and their interactions, to exercise hyperemia in the heart remain incompletely understood. In humans, nitric oxide, adenosine and K(ATP) channels each appear to contribute to resting coronary resistance vessel tone, but evidence for a critical contribution to exercise hyperemia is lacking. In dogs K(ATP)-channel activation together with adenosine and nitric oxide contribute to exercise hyperemia in a non-linear redundant fashion. In contrast, in swine nitric oxide, adenosine and K(ATP) channels contribute to resting coronary resistance vessel tone control in a linear additive manner, but do not appear to be mandatory for exercise hyperemia. Rather, exercise hyperemia in swine appears to involve beta-adrenergic activation in conjunction with exercise-induced blunting of an endothelin mediated vasoconstrictor influence. In view of these remarkable species differences in coronary vasomotor control during exercise, future studies are required to determine the system of vasodilator components that mediate exercise hyperemia in humans. This article is part of a Special Issue entitled "Coronary Blood Flow". PMID- 22037539 TI - A multi-CRD C-type lectin with broad recognition spectrum and cellular adhesion from Argopectenirradians. AB - C-type lectins are a superfamily of Ca(2+)-dependent carbohydrate-recognition proteins which play significant roles as pattern recognition receptors (PRRs) in the innate immunity. In this study, a novel C-type lectin with four dissimilar carbohydrate-recognition domains (CRDs) was identified from Argopectenirradians (designated as AiCTL-9). The full-length cDNA of AiCTL-9 was of 2291 bp with an open reading frame of 1827 bp encoding a polypeptide of 608 amino acids with a signal sequence and four CRDs. The motifs determining carbohydrate binding specificity in each CRD of AiCTL-9 were different, and they were YPT in CRD1, EPD in CRD2, EPN in CRD3 and QPN in CRD4, respectively. All the four CRDs shared the similar potential tertiary structure of a typical double-loop structure with Ca(2+)-binding site 2 in the long loop region and two conserved disulfide bridges at the bases of the loops. The mRNA transcripts of AiCTL-9 were mainly detected in hepatopancreas as well as gonad, and also marginally detectable in mantle, adductor, gill and hemocytes. Its relative expression level in hemocytes was significantly up-regulated after the challenges of fungi PichiapastorisGS115 (P<0.05), Gram-positive bacteria Micrococcusluteus (P<0.05) and Gram-negative bacteria Vibrioanguillarum (P<0.01). The recombinant AiCTL-9 (rAiCTL-9) could bind various PAMPs, including LPS, PGN, mannan and glucan, and also displayed agglutinating activity to fungi P. pastorisGS115, Gram-positive bacteria Bacillussubtilis and Gram-negative bacteria EscherichiacoliTOP10F' as well as V. anguillarum in a Ca(2+) dependent manner. Moreover, rAiCTL-9 could initiate the cellular adhesion of hemocytes and enhance their encapsulation invitro. All these results implied that AiCTL-9 was a novel PRR involved in immune response of scallop against a large number of pathogens by recognizing different PAMPs and enhancing scallop hemocytes encapsulation. PMID- 22037540 TI - A graphene oxide platform for the assay of biomolecules based on chemiluminescence resonance energy transfer. AB - The bifunctionality of graphene oxide (GO) that can highly adsorb single-stranded DNA (ssDNA) and effectively quench the emission of organic dyes is reasonably utilized in a chemiluminescence resonance energy transfer (CRET) system, achieving sensitive and selective detection of DNA (H1V1) and protein (thrombin), respectively. PMID- 22037541 TI - Cardiac resynchronization therapy after coronary sinus lead extraction: feasibility and mid-term outcome of transvenous reimplantation in a tertiary referral centre. AB - AIMS: Few data are available on cardiac resynchronization therapy (CRT) after coronary sinus (CS) lead extraction. We aimed to evaluate the feasibility and mid term outcome of transvenous CS lead reimplantation in a tertiary referral centre. METHODS AND RESULTS: We enrolled all patients who were referred to our hospital for CS lead removal from December 2000 through to May 2009 and were transvenously reimplanted with a CRT system before June 2009. One-year follow-up was performed to evaluate the incidence of infections, malfunctions, and mortality. We studied 113 consecutive patients undergoing successful CS lead extraction; 90 patients (75 male, mean age 69.2, range 35-84) underwent CS lead reimplantation (success rate: 95.6%; right-sided approach: 64.4%). In these patients, cardiac device infection was the usual indication for extraction (74.4%) and the subsequent reimplantation was performed after a median time of 3 days. The coronary sinus lead was usually positioned in the left ventricular (LV) postero-lateral region (62.2%); two procedures were required in two cases (2.2%). Balloon angioplasty was necessary for two patients (failure in one), whereas for the others we used a conventional implant technique. During follow-up, we observed four cases (4.4%) of local infection and six cases (6.7%) of system malfunction, requiring reintervention (two cases during the same hospitalization). One-year mortality was 5.5%. CONCLUSION: Left ventricular lead reimplantation is in our experience an effective and safe procedure, also in the case of right-sided approach. During follow-up, 1-year mortality was particularly low, whereas overall infection rate was higher than first implant procedures. PMID- 22037542 TI - Analysis of J waves during myocardial ischaemia. AB - AIMS: The aim of this study was to investigate the relationship between J-wave dynamics and arrhythmias during myocardial ischaemia in patients with vasospastic angina (VSA). METHODS AND RESULTS: Sixty-seven consecutive patients diagnosed with VSA by a provocation test for coronary spasm were grouped according to whether they had a J wave in the baseline electrocardiograms or not (VSA-JW group, n = 14; VSA-non-JW group: n = 53). We retrospectively studied the associations between J-wave and ST-segment dynamics and induced ventricular fibrillations (VFs) during coronary spasm. In the VSA-JW group, 7 of the 14 patients showed changes in J-wave morphology and/or gains in J-wave voltage, followed by VF in 4 patients. Compared with patients without VF, the four patients with VF showed similar maximal voltage in the baseline J waves but a higher voltage during induced coronary spasms (0.57 +/- 0.49 vs. 0.30 +/- 0.11 mV; P = 0.011). In three patients with VF, J waves progressively increased and were accompanied by the characteristic coved-type or lambda-shaped ST-segment elevations. In the VSA-non-JW group, only four patients showed new appearances of J waves during coronary spasms and another patient without a distinct J wave developed VF. Ventricular fibrillations were induced more frequently in the VSA JW group than in the VSA-non-JW group [4/14 (29%) vs. 1/53 (2%); P = 0.012]. CONCLUSION: J-wave augmentations were caused by myocardial ischaemia during coronary spasms. The presence and augmentation of J waves, especially prominent J waves with the characteristic ST-elevation patterns, were associated with VF. PMID- 22037543 TI - Correlation, accuracy, precision and practicability of perioperative measurement of sublingual temperature in comparison with tympanic membrane temperature in awake and anaesthetised patients. AB - BACKGROUND AND OBJECTIVE: The prevention of inadvertent perioperative hypothermia requires precise, reliable and practical methods of temperature measurement in both awake and anaesthetised patients. Different methods and sites of monitoring have been evaluated, but many are imprecise, unusable in awake patients, difficult to apply or too invasive, especially for minor surgery. The aim of this study was to evaluate the performance of perioperative sublingual and tympanic temperature measurement in awake and anaesthetised patients. METHODS: We enrolled 171 patients, aged 18-75 years, scheduled for surgery with duration less than 1 h under general anaesthesia. Spearman's rank correlation and Bland-Altman analysis for assessment of correlation, accuracy and precision of both methods were determined analysing 171 independent paired values at three different measurement times. RESULTS: Sublingual temperatures were significantly higher than tympanic temperatures by 0.1-0.2 degrees C. The coefficient of determination (r) of both methods was between 0.50 and 0.59, and Bland-Altman analysis revealed a bias (SD) of between -0.09 (0.21) and -0.15 (0.24) degrees C. CONCLUSION: The accuracy and precision of sublingual temperature measurement were adequate for clinical use, and there was a high correlation with tympanic temperature monitoring. Sublingual temperature measurement has been demonstrated as a good and practical modality for perioperative temperature monitoring in both awake and anaesthetised patients. PMID- 22037545 TI - ECG changes during in-situ hypothermic liver resections. PMID- 22037547 TI - Partial-post Laplace barriers for virtual confinement, stable displacement, and >5 cm s(-1) electrowetting transport. AB - Laplace barriers composed of full-posts or ridges have been previously reported as a mechanism for virtual fluid confinement, but with unstable displacement (capillary fingering or fluid trapping, respectively). A new platform of 'partial posts' eliminates the disadvantages of full-posts or ridges, while providing ~60 80% open channel area for rapid electrowetting fluid transport (>5 cm s(-1)). The fluid mechanics of partial-post Laplace barriers are far more complex than previous Laplace barriers as it involves two mechanisms: fluid can first begin to propagate either between, or under, the partial-posts. Careful design of channel and partial-post geometries is required, else one mechanism will dominate over the other. The physics and performance of partial-post Laplace barriers are verified using theoretical equations, experimental results, and dynamic numerical modeling. PMID- 22037546 TI - Susceptibility to oxidative stress and modulated expression of antioxidant genes in the copper-exposed polychaete Perinereis nuntia. AB - To identify and evaluate potentially useful biomarkers for oxidative stress as early warning indices in the polychaete, Perinereis nuntia, we exposed P. nuntia to copper (Cu) and measured several biomarker enzymes (glutathione S-transferase; GST, glutathione peroxidase; GPx, Metallothionein-like protein; MTLPs, and catalase; CAT) and genes (Pn-GSTs, Pn-CAT, and Pn-MT) with a cellular oxidative index, reactive oxygen species (ROS) level. Accumulated Cu concentrations in P. nuntia increased in a time-dependent manner. Intracellular ROS reached high levels 6h after exposure in P. nuntia with an increase of GST activity and glutathione (GSH) content. Particularly, GSH in polychaetes showed a positive correlation with Cu contents accumulated in P. nuntia. Messenger RNA expressions of GST sigma and GST omega showed relatively high expressions at 50 MUg/L of Cu exposure, even though the moderate increase of rest of GST isoforms was also observed. Also regarding long-term exposure, we reared P. nuntia in sediments for 15 days, and found that there was an obvious increase of Pn-GSTs, Pn-CAT, and Pn MT genes with elevated concentrations of Cu and Cd in polychaete body, compared to initial levels, suggesting that P. nuntia in sediment was affected by metals as well as by other organic pollutants to induce oxidative stress genes and enzymes. These findings suggest that oxidative stress is a potential modulator of defense system of P. nuntia. Several potential biomarker genes are available as early warning signals for environmental biomonitoring. PMID- 22037548 TI - Positive Borrelia burgdorferi serology secondary to intravenous immunoglobulin therapy. PMID- 22037549 TI - MicroRNA changes in human arterial endothelial cells with senescence: relation to apoptosis, eNOS and inflammation. AB - A senescent phenotype in endothelial cells is associated with increased apoptosis, reduced endothelial nitric oxide synthase (eNOS) and inflammation, which are implicated in arterial dysfunction and disease in humans. We tested the hypothesis that changes in microRNAs are associated with a senescent phenotype in human aortic endothelial cells (HAEC). Compared with early-passage HAEC, late passage HAEC had a reduced proliferation rate and increased staining for senescence-associated beta-galactosidase and the tumor suppressor p16(INK4a). Late-passage senescent HAEC had reduced expression of proliferation stimulating/apoptosis-suppressing miR-21, miR-214 and miR-92 and increased expression of tumor suppressors and apoptotic markers. eNOS-suppressing miR-221 and miR-222 were increased and eNOS protein and eNOS activation (phosphorylation at serine1177) were lower in senescent HAEC. Caveolin-1 inhibiting miR-133a was reduced and caveolin-1, a negative regulator of eNOS activity, was elevated in senescent HAEC. Inflammation-repressing miR-126 was reduced and inflammation stimulating miR-125b was increased, whereas inflammatory proteins were greater in senescent HAEC. Development of a senescent arterial endothelial cell phenotype featuring reduced cell proliferation, enhanced apoptosis and inflammation and reduced eNOS is associated with changes in miRNAs linked to the regulation of these processes. Our results support the hypothesis that miRNAs could play a critical role in arterial endothelial cell senescence. PMID- 22037550 TI - Interleukin-17A stimulates cardiac fibroblast proliferation and migration via negative regulation of the dual-specificity phosphatase MKP-1/DUSP-1. AB - The dual-specificity mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP 1) inactivates MAP kinases by dephosphorylation. Here we show that the proinflammatory cytokine interleukin (IL)-17A induces adult mouse primary cardiac fibroblast (CF) proliferation and migration via IL-17 receptor A//IL-17 receptor C-dependent MKP-1 suppression, and activation of p38 MAPK and ERK1/2. IL-17A mediated p38 MAPK and ERK1/2 activation is inhibited by MKP-1 overexpression, but prolonged by MKP-1 knockdown. IL-17A induced miR-101 expression via PI3K/Akt, and miR-101 inhibitor reversed MKP-1 down regulation. Importantly, MKP-1 knockdown, pharmacological inhibition of p38 MAPK and ERK1/2, or overexpression of dominant negative MEK1, each markedly attenuated IL-17A-mediated CF proliferation and migration. Similarly, IL-17F and IL-17A/F heterodimer that also signal via IL 17RA/IL-17RC, stimulated CF proliferation and migration. These results indicate that IL-17A stimulates CF proliferation and migration via Akt/miR-101/MKP-1 dependent p38 MAPK and ERK1/2 activation. These studies support a potential role for IL-17 in cardiac fibrosis and adverse myocardial remodeling. PMID- 22037551 TI - A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. AB - Gastric cancer, including the cardia and non-cardia types, is the second leading cause of cancer-related deaths worldwide. To identify genetic risk variants for non-cardia gastric cancer, we performed a genome-wide association study in 3,279 individuals (1,006 with non-cardia gastric cancer and 2,273 controls) of Chinese descent. We replicated significant associations in an additional 6,897 subjects (3,288 with non-cardia gastric cancer and 3,609 controls). We identified two new susceptibility loci for non-cardia gastric cancer at 5p13.1 (rs13361707 in the region including PTGER4 and PRKAA1; odds ratio (OR) = 1.41; P = 7.6 * 10(-29)) and 3q13.31 (rs9841504 in ZBTB20; OR = 0.76; P = 1.7 * 10(-9)). Imputation analyses also confirmed previously reported associations of rs2294008 and rs2976392 on 8q24, rs4072037 on 1q22 and rs13042395 on 20p13 with non-cardia gastric cancer susceptibility in the Han Chinese population. PMID- 22037552 TI - Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. AB - To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 * 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 * 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 * 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 * 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 * 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 * 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia. PMID- 22037553 TI - A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor negative breast cancer. AB - Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 * 10( 10)). The variant was also significantly associated with triple-negative (ER negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 * 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 * 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations. PMID- 22037554 TI - Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. AB - Gastric cancer is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis. Beyond mutations in TP53, alterations in other genes or pathways account for only small subsets of the disease. We performed exome sequencing of 22 gastric cancer samples and identified previously unreported mutated genes and pathway alterations; in particular, we found genes involved in chromatin modification to be commonly mutated. A downstream validation study confirmed frequent inactivating mutations or protein deficiency of ARID1A, which encodes a member of the SWI-SNF chromatin remodeling family, in 83% of gastric cancers with microsatellite instability (MSI), 73% of those with Epstein-Barr virus (EBV) infection and 11% of those that were not infected with EBV and microsatellite stable (MSS). The mutation spectrum for ARID1A differs between molecular subtypes of gastric cancer, and mutation prevalence is negatively associated with mutations in TP53. Clinically, ARID1A alterations were associated with better prognosis in a stage-independent manner. These results reveal the genomic landscape, and highlight the importance of chromatin remodeling, in the molecular taxonomy of gastric cancer. PMID- 22037556 TI - The unusual importance of activity coefficients for micelle solutions illustrated by an osmometry study of aqueous sodium decanoate and aqueous sodium decanoate + sodium chloride solutions. AB - Freezing-point and vapor-pressure osmometry data are reported for aqueous sodium decanoate (NaD) solutions and aqueous NaD + NaCl solutions. The derived osmotic coefficients are analyzed with a mass-action model based on the micelle formation reaction qNa(+) + nD(-) = (Na(q)D(n))(q-n) and Guggenheim equations for the micelle and ionic activity coefficients. Stoichiometric activity coefficients of the NaD and NaCl components and the equilibrium constant for micelle formation are evaluated. Illustrating the remarkable but not widely appreciated nonideal behavior of ionic surfactant solutions, the micelle activity coefficient drops to astonishingly low values, below 10(-7) (relative to unity for ideal solutions). The activity coefficients of the Na(+) and D(-) ions, raised to large powers of q and n, reduce calculated extents of micelle formation by up to 15 orders of magnitude. Activity coefficients, frequently omitted from the Gibbs equation, are found to increase the calculated surface excess concentration of NaD by up to an order of magnitude. Inflection points in the extent of micelle formation, used to calculate critical micelle concentration (cmc) lowering caused by added salt, provide unexpected thermodynamic evidence for the elusive second cmc. PMID- 22037555 TI - Common variants on 8p12 and 1q24.2 confer risk of schizophrenia. AB - Schizophrenia is a severe mental disorder affecting ~1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 * 10(-10)) and 1q24.2 (rs10489202, P = 9.50 * 10(-9)). Our findings provide new insights into the pathogenesis of schizophrenia. PMID- 22037557 TI - Listeriosis: An emerging public health problem especially among the elderly. AB - OBJECTIVES: To analyze the incidence trend of listeriosis, its present epidemiology and the potential benefit of aminoglycosides during the last two decades. METHODS: We reviewed all cases of invasive listeriosis detected during a 22-year period in a large tertiary hospital. Two equal periods of 11 years were compared. RESULTS: We detected 111 cases of listeriosis (32 during the first 11 year period and 79 during the second). Incidence of listeriosis increased significantly (from 4.66/10(6) inhabitants to 10.39/10(6) inhabitants; P = .001). In the second period, there were more patients >65 years (21.9%-45.6%; P = .02) and with no significant underlying diseases (0 vs. 16.5%; P = .02). Comparing clinical presentations between the two periods, primary bacteremia increased (40.6% vs. 55.7%), while central nervous system infections decreased (34.4% vs. 27.8%). Cotrimoxazole (SXT) use increased significantly in the second period (from 6.3% to 40.5%, P = .001) while the administration of aminoglycosides decreased (from 40.6% to 21.5%, P = .04). The use of combination therapy did not have any impact on mortality, however it did increase toxicity. CONCLUSIONS: Listeriosis should be considered an emerging health problem, especially among the elderly, including those with no underlying medical conditions. The use of aminoglycosides does not seem to be justified according to our data. PMID- 22037558 TI - Depressive symptoms during adolescence: comparison between epidemiological and high risk sampling. AB - PURPOSE: Both epidemiological (unselected) and high risk (screening on known risk criteria) samplings have been used to investigate the course of affective disorders. Selecting individuals on multiple risk criteria may create a sample not comparable to individuals with similar risk criteria within the general population. This study compared depressive symptoms across the two sampling methods to test this possibility. METHODS: The high risk Cambridge Hormones and Moods Project (CHAMP) screened and recruited adolescents aged 12 to 16. A total of 905 (710 high risk) individuals participated and were reassessed at three follow-ups. The ROOTS epidemiological sample consisted of 1,208 14-year-olds reassessed at 15.5 and 17 years. The risk profile for CHAMP was recreated in the ROOTS study. Both samples completed the Moods and Feelings Questionnaire, a self report measure of current depressive symptoms. RESULTS: Comparing individuals with the same high risk profiles across the CHAMP and ROOTS studies revealed no significant differences in mean depression scores. Combining the samples revealed that for females, mean depression scores were maintained from 12 to 15 years then declined by 17 years. For males, scores declined from 12 throughout adolescence. High risk status led to consistently higher levels of depressive symptoms in female adolescents but result in little change within male adolescents. CONCLUSIONS: The high risk design recruited adolescents with a depression symptoms profile comparable to the general population for both sexes. High risk status may alter the trajectory of depressive symptoms in female adolescents only. Males may be less sensitive to recent adversity. PMID- 22037559 TI - Oral opioid analgesics vs. spinal steroid injections in the treatment of low back pain syndromes. AB - OBJECTIVE: The aim of this study was to examine the outcomes related to analgesia, function, mortality, and adverse effects of oral opioid analgesics and spinal steroid injections on low back pain syndromes. DESIGN: Databases including Medline, EMBASE, PubMed, and Cochrane Library were searched in September 2009 using combinations of terms related to spinal pain and its treatment. A systematic review was performed of randomized controlled trials that enrolled patients with low back pain syndromes and that evaluated patient outcomes after intervention using either oral opioids or spinal steroid injections. RESULTS: Eight high-quality and ten moderate-quality randomized controlled trials were identified. One high-quality study on oral opioid therapy showed significant improvements in pain relief and patient function. Those on spinal steroid injections had a decreased Visual Analog Scale pain score by 7.18 (95% confidence interval, 2.21-12.1) points more than the control group at 1 mo or less and by 0.429 (95% confidence interval, -4.41 to 5.27) points at 1-3 mos. At more than 6 mos, there was no significant benefit: 0.930 (95% confidence interval, -5.03 to 6.89). Spinal steroids decreased the Oswestry Disability Index by 3.53 (95% confidence interval, 0.480-6.57) at 1 mo or less, by -0.281 (95% confidence interval, -3.18 to 2.62) at 1-3 mos, by -11.0 (95% confidence interval, -14.8 to 7.16) at 3-6 mos, and by -0.205 (95% confidence interval, -3.50 to 3.09) compared with the control group at 6 mos or more, suggesting that there was improvement in function. All-cause mortality was low in our analysis of patients attending specialty clinics. It was difficult to assess the adverse effects of opioid therapy because they influenced up to 28% of patients to withdraw from the original studies. In terms of spinal steroid injections, headache appeared to be the most common adverse effect. However, there was no significantly increased risk of headaches associated with spinal steroids compared with control injections: odds ratio, 1.29 (95% confidence interval, 0.69-2.39). CONCLUSIONS: Oral opioid therapy may be helpful for the treatment of low back pain, but it is unclear from the high-quality literature whether there are limitations from adverse effects. Spinal steroid injections are beneficial for low back pain and disability in the short-term. The high dropout rates caused by insufficient pain relief and adverse effects suggest that opioids may not be as effective as spinal steroid injections. There is more high-quality literature to support the use of spinal steroid injections compared with oral opioids in this condition. PMID- 22037560 TI - [Management of bleeding disorders in intensive care medicine]. AB - Bleeding disorders are frequent in intensive care medicine, the most common form being acquired. Trauma, gastrointestinal bleeding, liver failure, hematologic malignancies, and adverse drug reactions play an important role. Moderate to severe hereditary bleeding disorders are usually known prior to the acute disease state, while mild hereditary forms may manifest for the first time in association with the acute stress condition. Generally, proper history taking and structured observation are decisive in order to conduct an appropriate diagnostic workup and initiate logical hemostatic management. One cannot always wait for laboratory results during continuous blood loss or conditions such as hypothermia and acidosis. In such cases, pathophysiological extrapolation of expected hemostatic disturbances is essential for timely hemostatic management. PMID- 22037561 TI - [Supplemental parenteral nutrition. Friend or foe? The EPaNIC study]. PMID- 22037562 TI - Pharmacokinetics, safety, and tolerability of ribavirin in hemodialysis-dependent patients. AB - PURPOSE: This study describes the pharmacokinetics, safety, and tolerability of ribavirin in hemodialysis-dependent patients. METHODS: Six adult patients (4 male, 2 female) were recruited from a hemodialysis clinic where they were receiving regular hemodialysis sessions. Patients received a single oral 400-mg dose of ribavirin (2 * 200-mg capsules) after an overnight fast. A 4-h hemodialysis session was performed between 6 and 10 h post-dose. Plasma and urinary concentrations of ribavirin were determined using validated high performance liquid chromatography/tandem mass spectrometric methods. RESULTS: Single oral doses of ribavirin 400 mg were safe and well tolerated in this population. Urinary excretion of ribavirin over 48 h was minimal (0.6 mg: approximately 0.14% of the dose). The mean amount removed during the 4-h hemodialysis session (9.6 mg) represented approximately 2.4% of the dose. CONCLUSIONS: Ribavirin hemodialysis clearance (CLhd = 74.5 ml/min) represented approximately 50% of the renal clearance (CLr) measured in subjects with normal renal function (CLr = 129 ml/min). PMID- 22037563 TI - Pharmacokinetics of the local anesthetic ropivacaine after transversus abdominis plane block in healthy volunteers. AB - PURPOSE: The transversus abdominis plane (TAP) block is a regional anesthetic technique used for pain control following abdominal surgical procedures. While a minimum of systemic side effects is usually expected after local anesthesia, it is unknown to which extent systemic absorption and redistribution to the abdominal wall contributes to the effects of anesthetics. The aim of this study was to determine concentration-time profiles of ropivacaine after the injection of 150 mg of ropivacaine into the lateral abdominal wall in various compartments. METHODS: The microdialysis technique was used to measure ropivacaine in plasma as well as at abdominal wall sites cranial from the injection site (below the 12th rip) and caudal from the injection site (cranial from the iliac crest) and in the skeletal muscle tissue of the contra lateral thigh of eight healthy volunteers. RESULTS: The mean exposure to ropivacaine measured as the area under the concentration-time curve was significantly higher at the two abdominal sites (240.9 +/- 409.1 and 86.18 +/- 133.50 MUg h/mL, respectively) than in plasma (5.1 +/- 1.0 MUg h/mL) or in peripheral tissue (1.1 +/- 1.2 MUg h/mL). While the high mean concentrations of ropivacaine measured at the abdominal wall sites support the topical concept of the TAP block, the observed variability was striking. CONCLUSIONS: While the systemic pharmacokinetics was comparable between subjects, the local distribution of ropivacaine was highly variable after TAP block. PMID- 22037564 TI - Risk of caffeine toxicity associated with the use of 'legal highs' (novel psychoactive substances). AB - PURPOSE: Caffeine has desired stimulant effects similar to but weaker than both classical recreational drugs and novel psychoactive substances. This study was undertaken to determine the caffeine content of a sample of novel psychoactive substances, and we discuss the implications for the management of acute recreational drug toxicity. METHODS: Six novel psychoactive products ('legal highs') that were not declared to contain caffeine were purchased from different Internet suppliers; one additional product was supplied by the UK police force. Analysis of these products was undertaken using infrared spectroscopy (IR), gas chromatography with mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS-MS) to identify the active ingredient(s) and measure the caffeine content of the product. RESULTS: All seven products, which weighed approximately 1 g each, contained only caffeine as the active pharmacological compound. There was significant variation in the percentage caffeine content (<2 to 96%), with four powders containing very significant caffeine contents of 87-96%. CONCLUSION: This study shows that individuals are at risk of significant caffeine toxicity related to the high caffeine content of some novel psychoactive substances. Clinicians, including clinical pharmacologists, need to be aware of this to ensure that the management of acute recreational drug toxicity is appropriate and that over-correction of any hypokalaemia does not occur. PMID- 22037566 TI - Spinal epidural hematoma: not always an obvious diagnosis. AB - Spinal epidural hematoma (SEH) is a rare neurosurgical emergency. SEH is characterized by an archetypal clinical presentation including abrupt spinal pain followed more or less rapidly by various degrees of neurological deficit. The diagnosis of SEH, often based on a clinical presumption, represents a clinical challenge. Several reports have outlined missed or delayed diagnosis due to unusual and confusing onsets or unawareness of this diagnosis by physicians. Therefore, physicians should keep in mind the possibility of SEH in their differential diagnosis when confronted with patients complaining of sudden onset of acute spinal pain with or without neurological sign, because the impact of a delayed diagnosis can be disabling catastrophic neurological sequelae. We suggest that SEH is a dynamic disease, which occurs in patients with an abnormal vasculature structural degenerative change. The bleeding is probably of multifactorial origin incriminating veins as well as arteries. Therefore, we proposed a classification of SEH, according to the most probable etiology whatever the associated factors, in six groups: spontaneous, secondary, iatrogenic, traumatic, recurrent, and idiopathic SEH. PMID- 22037567 TI - Polyprenylated isoflavanone and isoflavonoids from Ormosia henryi and their cytotoxicity and anti-oxidation activity. AB - A rare naturally-occurring polyprenylated isoflavanone, designated ormosinol (1), and a new isoflavonoid glycoside, named ormosinoside (2), along with 21 known compounds were isolated from the root bark of Ormosia henryi Prain. The structures of compounds 1 and 2 were determined as 5,7,2',4'-tetrahydroxyl-6,8,5' tri-(gamma,gamma-dimethylallyl)isoflavanone and isoprunetin-7-O-beta-D xylopyranosyl-(1 -> 6)-beta-D-glucopyranoside on the basis of a combination of 1D , 2D-NMR and mass spectroscopic measurements. Compound 1 showed significant anti oxidation activity against DPPH radicals (IC(50) 28.5 MUM) and cancer cell line (A549, LAC, and HepG2) growth inhibitory activity with IC(50) ranging from 4.25 to 7.09 MUM, while compound 2 found to be inactive to both testing systems. PMID- 22037568 TI - A new alkaloid from Fritillaria ussuriensis Maxim. AB - Pingbeimunone A (1), a new compound, together with the known ussuriedine (2), benzo[7,8]fluoreno[2,1-b]quinolizine cevane-3,6,16,20-tetrol (3), ebeiedinone (4), pingbeimine C (5) and verticine (6) were isolated from Fritillaria ussuriensis. The structure was elucidated on the basis of spectral analysis (IR, NMR and MS spectroscopy). In addition, their AChE inhibitory activities were also tested. PMID- 22037569 TI - Characterization of a highly polymeric proanthocyanidin fraction from persimmon pulp with strong Chinese cobra PLA2 inhibition effects. AB - Persimmon proanthocyanidin was fractionated on Toyopearl TSK-HW-50-F to yield a fraction with strong inhibition on the catalytic activity and edema-inducing activity and lethality of Chinese cobra PLA(2). Thiolysis suggested that the terminal units included C, EGCG and myricetin, and epicatechin, epigallocatechin, (epi)gallocatechin-3-O-gallate, and (epi)catechin-3-O-gallate occurred as extender units. The mean degree of polymerization was 23.7. MALDI TOF/MS, thioly HPLC, FTIR and circular dichroism (CD) analyses showed that the fraction had high prodelphinidin content (55%) and a very high degree of 3-O-galloylation (92%). A type linkage is dominant in it and it had 4beta linkage of the flavanyl substituent and 4R absolute configuration. PMID- 22037570 TI - Dispensable role for 4-1BB and 4-1BBL in development of vaccinia virus-specific CD8 T cells. AB - CD8 T cells are strongly induced in response to certain strains of vaccinia virus (VACV) and the generation of this population is tightly regulated by two Tumor Necrosis Factor (TNF)/TNFR superfamily members, OX40 (CD134) and CD27. In this study, we examined the role of another member of the TNFR superfamily, 4-1BB (CD137, TNFRSF9), and its ligand (4-1BBL, CD137L, TNFSF9), that have been described to control the generation of memory CD8 T cell populations elicited by other viruses such as influenza. Expression of 4-1BB and 4-1BBL was observed in wild-type mice during the primary infection, but we found that both 4-1BB and 4 1BBL deficient mice generated normal numbers of VACV-specific effector CD8 T cells that produced IFN-gamma and TNF. Additionally, CD8 T cells deficient in 4 1BB were able to expand and persist comparably to wild-type T cells in response to VACV infection. Furthermore, the knockout mice also showed no defect in development of VACV-specific CD8 memory T cell populations. Lastly, showing alternate control mechanisms were not active in the gene-deficient environments that masked any activity, blocking 4-1BB/4-1BBL interactions using neutralizing antibody also had no effect on the number of VACV-specific memory CD8 T cells induced. Thus, our data demonstrate that 4-1BB and 4-1BBL do not play a strong or dominant role in driving the generation of high frequencies of VACV-specific CD8 T cells. PMID- 22037571 TI - Establishment and characterization of a murine model for allergic asthma using allergen-specific IgE monoclonal antibody to study pathological roles of IgE. AB - Allergen-specific IgE has long been regarded as a major molecular component of allergic asthma. Although IgE plays a central role in the early asthmatic response, its roles in the chronic phase, such as the late asthmatic response, airway hyperresponsiveness (AHR), and airway remodeling (goblet cell hyperplasia and subepithelial fibrosis) have not yet been defined well. In this study, we investigated the hypothesis that chronic responses could be induced by IgE dependent mechanisms. BALB/c mice passively sensitized with an ovalbumin (OVA) specific IgE monoclonal antibody (mAb) were repeatedly challenged with intratracheal administration of OVA. The first challenge induced early phase airway narrowing without any late response, but the fourth challenge caused not only an early but also a late phase response, AHR, and goblet cell hyperplasia. Macrophages, lymphocytes and neutrophils, but not eosinophils, were significantly increased in the lung 24h after the fourth challenge. Interestingly, levels of OVA-specific IgG1 in serum increased by multiple antigen challenges. A C3a receptor antagonist inhibited the late asthmatic response, AHR, and infiltration by neutrophils. In contrast, no late response, goblet cell hyperplasia, inflammatory cells, or production of IgG1 was observed in severe combined immunodeficient mice. On the other hand, seven challenges in BALB/c mice induced subepithelial fibrosis associated with infiltration by eosinophils. In conclusion, the allergic asthmatic responses induced by passive sensitization with IgE mAb can provide a useful model system to study the pathological roles of IgE in acute and chronic phases of allergic asthma. PMID- 22037572 TI - Control of postoperative pain with a wearable continuously operating pulsed radiofrequency energy device: a preliminary study. AB - BACKGROUND: Pulsed radiofrequency energy (PRFE) has long been reported to have a therapeutic effect on postoperative pain. In this study, a portable, wearable, low-energy-emitting PRFE therapy device was used to determine the control of postoperative pain after breast augmentation surgery. METHODS: The study enrolled 18 healthy women who underwent breast augmentation purely for aesthetic considerations. Postoperative pain after surgery was assessed with a 0- to 10 point visual analog scale (VAS). Baseline pain scores were taken at completion of the operation, and the patients were randomly assigned coded PRFE devices that were either active or placebo devices. For 7 days, VAS scores were recorded twice daily (a.m. and p.m.). Medication use also was logged for 7 days. The PRFE devices were left in place and in continuous operation for the 7 days of the study. RESULTS: All the patients tolerated the PRFE therapy well, and no side effects were reported. The VAS scores for the active group were significantly lower on postoperative day 1. By day 7, the baseline VAS remaining in the active group was 7.9% versus 38% in the placebo group. Together with lower VAS scores, narcotic pain medication use was lower in the patient group that received PRFE therapy. CONCLUSION: Postoperative pain is significantly lower with PRFE therapy. According to the findings, PRFE therapy in this form is an excellent, safe, drug free method of postoperative pain control. PMID- 22037573 TI - Transaxillary muscle-splitting breast augmentation: experience with 160 cases. AB - BACKGROUND: Muscle-splitting breast augmentation, initially described by Baxter and later popularized by Khan, has proved to be an effective technique in terms of implant coverage, bypassing, and even solving of some issues associated with the dual-plane technique. A muscle-splitting breast augmentation technique recently has been used in combination with mastopexy. However, no reports have described muscle-splitting techniques accomplished by the transaxillary route. METHODS: A prospective study was conducted to evaluate the outcomes and complications of a novel approach to a specific breast augmentation technique. A total of 160 patients underwent bilateral transaxillary muscle-splitting breast augmentation between October 2007 and July 2010. All the patients were treated on an outpatient basis and received epidural anesthesia. Soft, round, textured, cohesive gel implants ranging in size from 200 to 350 ml were used. RESULTS: All the patients recovered quickly. To date, no infection, capsular contracture, rippling, double-bubble deformity, muscle contracture-associated deformities, or implant migration has occurred. Four patients (2.5%) experienced hematomas, all of which resolved before discharge. All the patients were discharged less than 24 h postoperatively and had an aesthetically natural result. CONCLUSION: Transaxillary muscle-splitting breast augmentation, a novel approach to a technique that has been described previously, provides consistent, satisfactory results and good reproducibility. This new approach provides an excellent anatomic final appearance with no risk of displacement, rippling, double-bubble deformity, or contracture-associated deformities. Furthermore, this technique avoids any visible scars on the breast and features a low complication rate. PMID- 22037574 TI - Geometric incision design for reduction nippleplasty. AB - BACKGROUND: Nipple hypertrophy is a frequently encountered problem in Asian women. It may be congenital or caused by hormones, breast feeding, or gestation. The hypertrophy has been linked primarily to aesthetics. The nipples of Asian women usually are 6-10 mm in diameter and 5-8 mm in height, and women with nipples larger than 1.5 cm in diameter or height frequently ask for reduction nippleplasty. METHODS: Women with nipple hypertrophy seeking reductive surgery at the authors' hospital between 2004 and 2009 were considered for nippleplasty. A new design consisting of three dermal flaps and sparing of the central column was used. This design can reduce the diameter, height, and most importantly, the basal shape of the nipple without compromising neurovascular supply and functions. RESULTS: During the aforementioned period, 86 nipples of 43 patients were corrected with this method. All the patients were satisfied with the aesthetic results, preserved lactation, and sensory function. No major complications such as necrosis, infection, or numbness of the nipple occurred. CONCLUSIONS: This reduction nippleplasty method can be applied for all types of nipple hypertrophy to create a new nipple of the desired height and diameter without significant complications. PMID- 22037575 TI - Long-term complications of polyethylene glycol injection to the face. AB - Currently, filling, smoothing, or recontouring the face through the use of injectable fillers is one of the most popular forms of cosmetic surgery. Because these materials promise a more youthful appearance without anesthesia in a noninvasive way, various fillers have been used widely in different parts of the world. However, most of these fillers have not been approved by the Food and Drug Administration, and their applications might cause unpleasant disfiguring complications. This report describes a case of foreign body granuloma in the cheeks secondary to polyethylene glycol injection and shows the possible complications associated with the use of facial fillers. PMID- 22037576 TI - Force via integrins but not E-cadherin decreases Oct3/4 expression in embryonic stem cells. AB - Increasing evidence suggests that mechanical factors play a critical role in fate decisions of stem cells. Recently we have demonstrated that a local force applied via Arg-Gly-Asp (RGD) peptides coated magnetic beads to mouse embryonic stem (ES) cells increases cell spreading and cell stiffness and decreases Oct3/4 (Pou5f1) gene expression. However, it is not clear whether the effects of the applied stress on these functions of ES cells can be extended to natural extracellular matrix proteins or cell-cell adhesion molecules. Here we show that a local cyclic shear force applied via fibronectin or laminin to integrin receptors increased cell spreading and stiffness, downregulated Oct3/4 gene expression, and decreased cell proliferation rate. In contrast, the same cyclic force applied via cell-cell adhesion molecule E-cadherin (Cdh1) had no effects on cell spreading, Oct3/4 gene expression, and the self-renewal of mouse ES cells, but induced significant cell stiffening. Our findings demonstrate that biological responses of ES cells to force applied via integrins are different from those to force via E-cadherin, suggesting that mechanical forces might play different roles in different force transduction pathways to shape early embryogenesis. PMID- 22037577 TI - Novel regulatory role for Kaposi's sarcoma-associated herpesvirus-encoded vFLIP in chemosensitization to bleomycin. AB - Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is associated with malignancy. KSHV-derived vFLIP is structurally related to cellular FLIP and binds to NEMO/IkappaB kinase (IKKgamma) to activate NF-kappaB signaling. NF-kappaB activation is postulated to confer chemoresistance to various anticancer drugs. However, here we showed that vFLIP expression uniquely sensitized HEK293 cells to bleomycin and its derivatives. Chemosensitization to bleomycin by vFLIP accompanied accumulation of gamma-H2AX and G2/M-arrest of cells, while bleomycin induced DNA damage checkpoints, such as phosphorylation of Chk2 and foci formation of Rad51, were similarly detected in both parental and vFLIP-expressing cells, suggesting that primary DNA damage was not affected by vFLIP. Paradoxically, while NF-kappaB activity was little affected by bleomycin treatment, vFLIP-stimulated NF-kappaB activity was suppressed by it. Additionally, cAMP-response element (CRE)- and p53-dependent transcriptional reporter activity was negatively regulated by vFLIP in the presence of bleomycin. Interestingly, a negative regulatory phosphatase essential for G2 checkpoint recovery and for dephosphorylation of gamma-H2AX, Wip1/PPM1D, whose gene promoter is regulated by p53, CRE and NF-kappaB, was selectively downregulated in vFLIP expressing cells after bleomycin treatment. These results suggest that vFLIP mediated transcriptional regulation such as Wip1/PPM1D repression is involved in chemosensitization to bleomycin. PMID- 22037578 TI - Haploinsufficient and predominant expression of multiple endocrine neoplasia type 1 (MEN1)-related genes, MLL, p27Kip1 and p18Ink4C in endocrine organs. AB - Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominantly inherited syndrome characterized by parathyroid, gastro-entero-pancreatic and anterior pituitary tumors. Although the tissue selectivity of tumors in specific endocrine organs is the very essence of MEN1, the mechanisms underlying the tissue-selectivity of tumors remain unknown. The product of the Men1 gene, menin, and mixed lineage leukemia (MLL) have been found to cooperatively regulate p27(Kip1)/CDKN1B (p27) and p18(Ink4C)/CDKN2C (p18) genes. However, there are no reports on the tissue distribution of these MEN1-related genes. We investigated the expression of these genes in the endocrine and non-endocrine organs of wild type, Men1 knockout and MLL knockout mice. Men1 mRNA was expressed at a similar level in endocrine and non-endocrine organs. However, MLL, p27 and p18 mRNAs were predominantly expressed in the endocrine organs. Notably, p27 and MLL mRNAs were expressed in the pituitary gland at levels approximately 12- and 17-fold higher than those in the liver. The heterozygotes of Men1 knockout mice the levels of MLL, p27 and p18 mRNAs did not differ from those in the wild-type mice. In contrast, heterozygotes of MLL knockout mice showed significant reductions in p27 mRNA as well as protein levels in the pituitary and p27 and p18 in the pancreatic islets, but not in the liver. This study demonstrated for the first time the predominant expression MEN1-related genes, particularly MLL and p27, in the endocrine organs, and a tissue-specific haploinsuffiency of MLL, but not menin, may lead to a decrease in levels of p27 and p18 mRNAs in endocrine organs. These findings may provide basic information for understanding the mechanisms of tissue selectivity of the tumorigenesis in patients with MEN1. PMID- 22037579 TI - Transient expression of a viral histone H4 inhibits expression of cellular and humoral immune-associated genes in Tribolium castaneum. AB - A viral histone H4 is encoded in a polydnavirus called Cotesia plutellae bracovirus (CpBV), which is symbiotic to an endoparasitoid wasp, C. plutellae. Compared to general histone H4s, the viral H4 possesses an extra N-terminal tail containing 38 amino acid residues, which has been presumed to control host gene expression in an epigenetic mode. To analyze the epigenetic control activity of CpBV-H4 on expression of immune-associated genes, it was transiently expressed in larvae of Tribolium castaneum that had been annotated in the immune genes from a full genome sequence. Subsequent alteration of gene expression pattern was compared with that of its mutant form deleting N-terminal tail (truncated CpBV H4). In response to bacterial challenge, T. castaneum induces expression of 13 antimicrobial peptide (AMP) genes. When CpBV-H4 was expressed, the larvae failed to express 12 inducible AMP genes. By contrast, when truncated CpBV-H4 was transiently expressed, all AMP genes were expressed. Hemocyte nodule formation was significantly impaired by expression of CpBV-H4, in which expressions of tyrosine hydroxylase and dihydroxyphenylalanine decarboxylase were suppressed. However, expression of truncated CpBV-H4 did not give any significant adverse effect on the cellular immunity. The immunosuppression of CpBV-H4 was further supported by its activity of enhancing bacterial pathogenicity of an entomopathogenic bacterium, Xenorhabdus nematophila, against larvae transiently expressing CpBV-H4. These results suggest that CpBV-H4 suppresses both humoral and cellular immune responses of T. castaneum by altering a normal epigenetic control of immune-associated gene expression. PMID- 22037581 TI - New functional poly(N-vinylpyrrolidone) based (co)polymers via photoinitiated cobalt-mediated radical polymerization. AB - The photoinitiated cobalt-mediated radical polymerization enables the synthesis of novel alpha-functional and alpha,omega-telechelic polymers. In combination with ring-opening polymerization, it also produces new amphiphilic copolymers which self-assemble into flower-like vesicles in water. PMID- 22037580 TI - The plant limonoid 7-oxo-deacetoxygedunin inhibits RANKL-induced osteoclastogenesis by suppressing activation of the NF-kappaB and MAPK pathways. AB - Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. Aberrations in osteoclast differentiation and activity contribute to osteopenic disease. Osteoclasts differentiate from monocyte/macrophage progenitors, a process that is initiated by the interaction between receptor activator of NF kappaB (RANK) and its ligand, RANKL. In this study, we identified 7-oxo-7 deacetoxygedunin (7-OG), a gedunin type limonoid from seeds of the mangrove Xylocarpus moluccensis, as a potent inhibitor of osteoclastogenesis. Additionally, 7-OG showed strong anti-osteoclastogenic activity with low cytotoxicity against the monocyte/macrophage progenitor cell line, RAW264.7. The IC50 for anti-osteoclastogenic activity was 4.14MUM. Treatment with 7-OG completely abolished the appearance of multinucleated giant cells with tartrate resistant acid phosphatase activity in RAW264.7 cells stimulated with RANKL. When the expression of genes related to osteoclastogenesis was investigated, a complete downregulation of NFATc1 and cathepsin K and a delayed downregulation of irf8 were observed upon 7-OG treatment in the presence of RANKL. Furthermore, treatment with this limonoid suppressed RANKL-induced activation of p38, MAPK and Erk and nuclear localization of NF-kappaB p65. Taken together, we present evidence indicating a plant limonoid as a novel osteoclastogenic inhibitor that could be used for osteoporosis and related conditions. PMID- 22037582 TI - Crystal structure of human prostate-specific antigen in a sandwich antibody complex. AB - Human prostate-specific antigen (PSA or human kallikrein-related peptidase 3) present in small quantities in the sera of healthy men becomes elevated in prostate cancer (PCa) and other prostate disorders. The ability to identify the free PSA fraction associated with PCa could increase the reliability of the PSA diagnostic test. Here we present the crystal structure of human PSA from seminal fluid in a sandwich complex with two monoclonal antibodies (mAbs). MAb 5D5A5 captures total PSA with exceptionally high affinity, and mAb 5D3D11 selectively discriminates between free PSA subforms that are more abundant in sera from patients with PCa. Although the antigen is not of seric origin, several insights into cancer diagnosis can be discerned from this complex. MAb 5D3D11 recognizes a PSA conformation different from that previously reported. Interacting with the kallikrein loop, the PSA N-linked glycan attached to asparagine 61 is an uncommonly complex sialated triantennary chain. O-linked glycosylation is observed at threonine 125. The description of how PSA subforms in prostatic fluid can be discriminated using pairs of antibodies is a first step in the design of new strategies that are capable of real discrimination among PSA subforms, which will lead to the formulation of more reliable diagnostic tests. In a companion article [Muller, B. H., Savatier, A., L'Hostis, G., Costa, N., Bossus, M., Michel, S., et al. (2011). In vitro affinity maturation of an anti-PSA antibody for prostate cancer diagnostic assay. J. Mol. Biol.], we describe engineering efforts to improve the affinity of mAb 5D3D11, a first step towards such goal. PMID- 22037584 TI - Barriers and silencers: a theoretical toolkit for control and containment of nucleosome-based epigenetic states. AB - Positive feedback in nucleosome modification has been proposed to allow large chromatin regions to exist stably and heritably in distinct expression states. However, modeling has shown that such epigenetic bistability requires that modifying enzymes recruited by nucleosomes are active on distant nucleosomes, potentially allowing uncontrollable spreading of modification. By modeling the silencing of mating-type loci in Saccharomyces cerevisiae, we show that a modification reaction that combines a long-range component and a locally acting component can provide bistability and can be blocked by simple barriers that interrupt the nucleosome chain. We find that robust containment of the silenced region could be achieved by the presence of a number of weak simple barriers in the surrounding chromatin and a limited capacity of the positive feedback reaction. In addition, we show that the state of the silenced region can be regulated by silencer elements acting only on neighboring nucleosomes. Thus, a relatively simple set of nucleosome-modifying enzymes and recognition domains is all that is needed to make chromatin-based epigenetics useful and safe. PMID- 22037583 TI - The scope of phage display for membrane proteins. AB - Numerous examples of phage display applied to soluble proteins demonstrate the power of the technique for protein engineering, affinity reagent discovery and structure-function studies. Recent reports have expanded phage display to include membrane proteins (MPs). The scope and limitations of MP display remain undefined. Therefore, we report data from the phage display of representative types of membrane-associated proteins including plasma, nuclear, peripheral, single and multipass. The peripheral MP neuromodulin displays robustly with packaging by conventional M13-KO7 helper phage. The monotopic MP Nogo-66 can also display on the phage surface, if packaged by the modified M13-KO7(+) helper phage. The modified phage coat of KO7(+) can better mimic the zwitterionic character of the plasma membrane. Four examples of putatively alpha-helical, integral MPs failed to express as fusions to an anchoring phage coat protein and therefore did not display on the phage surface. However, the beta-barrel MPs ShuA (Shigella heme uptake A) and MOMP (major outer membrane protein), which pass through the membrane 22 and 16 times, respectively, can display surprisingly well on the surfaces of both conventional and KO7(+) phages. The results provide a guide for protein engineering and large-scale mutagenesis enabled by the phage display of MPs. PMID- 22037586 TI - Molecular dynamics simulations of the effect of the G-protein and diffusible ligands on the beta2-adrenergic receptor. AB - G-protein-coupled receptors have extraordinary therapeutic potential as targets for a broad spectrum of diseases. Understanding their function at the molecular level is therefore essential. A variety of crystal structures have made the investigation of the inactive receptor state possible. Recently released X-ray structures of opsin and the beta(2)-adrenergic receptor (beta(2)AR) have provided insight into the active receptor state. In addition, we have contributed to the crystal structure of an irreversible agonist-beta(2) adrenoceptor complex. These extensive studies and biophysical investigations have revealed that agonist binding leads to a low-affinity conformation of the active state that is suggested to facilitate G-protein binding. The high-affinity receptor state, which promotes signal transduction, is only formed in the presence of both agonist and G-protein. Despite numerous crystal structures, it is not yet clear how ligands tune receptor dynamics and G-protein binding. We have now used molecular dynamics simulations to elucidate the distinct impact of agonist and inverse agonist on receptor conformation and G-protein binding by investigating the influence of the ligands on the structure and dynamics of a complex composed of beta(2)AR and the C-terminal end of the Galpha(s) subunit (GalphaCT). The simulations clearly showed that the agonist isoprenaline and the inverse agonist carazolol influence the ligand-binding site and the interaction between beta(2)AR and GalphaCT differently. Isoprenaline induced an inward motion of helix 5, whereas carazolol blocked the rearrangement of the extracellular part of the receptor. Moreover, in the presence of isoprenaline, beta(2)AR and GalphaCT form a stable interaction that is destabilized by carazolol. PMID- 22037585 TI - Structural basis for myopathic defects engendered by alterations in the myosin rod. AB - While mutations in the myosin subfragment 1 motor domain can directly disrupt the generation and transmission of force along myofibrils and lead to myopathy, the mechanism whereby mutations in the myosin rod influences mechanical function is less clear. Here, we used a combination of various imaging techniques and molecular dynamics simulations to test the hypothesis that perturbations in the myosin rod can disturb normal sarcomeric uniformity and, like motor domain lesions, would influence force production and propagation. We show that disrupting the rod can alter its nanomechanical properties and, in vivo, can drive asymmetric myofilament and sarcomere formation. Our imaging results indicate that myosin rod mutations likely disturb production and/or propagation of contractile force. This provides a unifying theory where common pathological cascades accompany both myosin motor and specific rod domain mutations. Finally, we suggest that sarcomeric inhomogeneity, caused by asymmetric thick filaments, could be a useful index of myopathic dysfunction. PMID- 22037587 TI - The field and temperature dependence of the magnetic and structural properties of the shape memory compound Ni(1.84)Mn(1.64)In(0.52). AB - Magnetization and high resolution neutron powder diffraction measurements have been made on the magnetic shape memory alloy Ni(1.84)Mn(1.64)In(0.52). The compound undergoes a broad structural phase transition, which on heating starts at ~150 K and finishes at ~215 K. On cooling there is a ~20 K hysteresis. The high temperature parent phase is cubic (a = 5.988 A) with the L2(1) structure in which the excess Mn atoms occupy the vacancies on the Ni and In sites. The magnetic moment is located mainly on the Mn atoms with the same magnitude on both the 4a (Mn) and 4b (In) sites. The low temperature martensite is monoclinic with parameters a = 4.405(2), b = 5.553(2), c = 12.950(2) A, beta = 86.47(10) degrees and space group P2/m. The magnetic properties of the martensitic phase are complex and indicate metamagnetic behaviour. PMID- 22037588 TI - Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: implications to mitochondria-targeted antioxidant therapeutics. AB - Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer's disease (AD) progression. Loss of synapses and synaptic damage are the best correlates of cognitive deficits found in AD patients. Recent research on amyloid beta (Abeta) and mitochondria in AD revealed that Abeta accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AbetaPP) transgenic mice revealed reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Abeta is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Abeta-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. PMID- 22037589 TI - Compromised mitochondrial complex II in models of Machado-Joseph disease. AB - Machado-Joseph disease (MJD), also known as Spinocerebellar Ataxia type 3, is an inherited dominant autosomal neurodegenerative disorder. An expansion of Cytosine Adenine-Guanine (CAG) repeats in the ATXN3 gene is translated as an expanded polyglutamine domain in the disease protein, ataxin-3. Selective neurodegeneration in MJD is evident in several subcortical brain regions including the cerebellum. Mitochondrial dysfunction has been proposed as a mechanism of neurodegeneration in polyglutamine disorders. In this study, we used different cell models and transgenic mice to assess the importance of mitochondria on cytotoxicity observed in MJD. Transiently transfected HEK cell lines with expanded (Q84) ataxin-3 exhibited a higher susceptibility to 3 nitropropionic acid (3-NP), an irreversible inhibitor of mitochondrial complex II. Increased susceptibility to 3-NP was also detected in stably transfected PC6 3 cells that inducibly express expanded (Q108) ataxin-3 in a tetracycline regulated manner. Moreover, cerebellar granule cells from MJD transgenic mice were more sensitive to 3-NP inhibition than wild-type cerebellar neurons. PC6-3 (Q108) cells differentiated into a neuronal-like phenotype with nerve growth factor (NGF) exhibited a significant decrease in mitochondrial complex II activity. Mitochondria from MJD transgenic mouse model and lymphoblast cell lines derived from MJD patients also showed a trend toward reduced complex II activity. Our results suggest that mitochondrial complex II activity is moderately compromised in MJD, which may designate a common feature in polyglutamine toxicity. PMID- 22037592 TI - Acrolein hydrogenation on Pt(211) and Au(211) surfaces: a density functional theory study. AB - Partial hydrogenation of acrolein, the simplest alpha,beta-unsaturated aldehyde, is not only a model system to understand the selectivity in heterogeneous catalysis, but also technologically an important reaction. In this work, the reaction on Pt(211) and Au(211) surfaces is thoroughly investigated using density functional theory calculations. The formation routes of three partial hydrogenation products, namely propenol, propanal and enol, on both metals are studied. It is found that the pathway to produce enol is kinetically favoured on Pt while on Au the route of forming propenol is preferred. Our calculations also show that the propanal formation follows an indirect pathway on Pt(211). An energy decomposition method to analyze the barrier is utilized to understand the selectivities at Pt(211) and Au(211), which reveals that the interaction energies between the reactants involved in the transition states play a key role in determining the selectivity difference. PMID- 22037591 TI - Two-dimensional paper networks: programmable fluidic disconnects for multi-step processes in shaped paper. AB - Most laboratory assays take advantage of multi-step protocols to achieve high performance, but conventional paper-based tests (e.g., lateral flow tests) are generally limited to assays that can be carried out in a single fluidic step. We have developed two-dimensional paper networks (2DPNs) that use materials from lateral flow tests but reconfigure them to enable programming of multi-step reagent delivery sequences. The 2DPN uses multiple converging fluid inlets to control the arrival time of each fluid to a detection zone or reaction zone, and it requires a method to disconnect each fluid source in a corresponding timed sequence. Here, we present a method that allows programmed disconnection of fluid sources required for multi-step delivery. A 2DPN with legs of different lengths is inserted into a shared buffer well, and the dropping fluid surface disconnects each leg at in a programmable sequence. This approach could enable multi-step laboratory assays to be converted into simple point-of-care devices that have high performance yet remain easy to use. PMID- 22037590 TI - Canine epilepsy genetics. AB - There has been much interest in utilizing the dog as a genetic model for common human diseases. Both dogs and humans suffer from naturally occurring epilepsies that share many clinical characteristics. Investigations of inherited human epilepsies have led to the discovery of several mutated genes involved in this disease; however, the vast majority of human epilepsies remain unexplained. Mouse models of epilepsy exist, including single-gene spontaneous and knockout models, but, similar to humans, other, polygenic models have been more difficult to discern. This appears to also be the case in canine epilepsy genetics. There are two forms of canine epilepsies for which gene mutations have been described to date: the progressive myoclonic epilepsies (PMEs) and idiopathic epilepsy (IE). Gene discovery in the PMEs has been more successful, with eight known genes; six of these are orthologous to corresponding human disorders, while two are novel genes that can now be used as candidates for human studies. Only one IE gene has been described in dogs, an LGI2 mutation in Lagotto Romagnolos with a focal, juvenile remitting epilepsy. This gene is also a novel candidate for human remitting childhood epilepsy studies. The majority of studies of dog breeds with IE, however, have either failed to identify any genes or loci of interest, or, as in complex mouse and human IEs, have identified multiple QTLs. There is still tremendous promise in the ongoing canine epilepsy studies, but if canine IEs prove to be as genetically complex as human and murine IEs, then deciphering the bases of these canine epilepsies will continue to be challenging. PMID- 22037593 TI - Effect of physician collaboration network on hospitalization cost and readmission rate. AB - BACKGROUND: Previous studies have documented the effect of collaboration among physicians on the effectiveness in delivering health services and in producing better patient outcomes. However, there is no systematic empirical study suggesting the underlying relationship between the collaboration network of physicians and its effect on hospitalization cost and readmission rate. In this study, we explore the effect of different attributes (i.e. degree centrality, betweenness centrality, network density and network distance) of physician collaboration network (PCN) on hospitalization cost and readmission rate. METHOD: We analyse health insurance claim data set of total hip replacement (THR) patients to construct PCN and to test the effect of its network attributes on hospitalization cost and readmission rate. We consider patient age as moderating factor, which could affect the relation of the PCN attributes with hospitalization cost and readmission rate. RESULTS: We find that degree centrality (i.e. level of involvement) and network density (i.e. level of connectedness) of PCN are negatively correlated with hospitalization cost and readmission rate. In contrast, betweenness centrality (i.e. capacity to control the flow of information) is found positively correlated with hospitalization cost and readmission rate. Distance (i.e. embeddedness of actors in a network) is found positively correlated with hospitalization cost but negatively correlated with readmission rate. We do not notice any significant impact of patient age on the relation of PCN attributes with hospitalization cost and readmission rate. CONCLUSION: The results show that the structure of PCNs is related to indicators of hospital costs and quality (readmission). In their respective hospitals, health-care managers or administrators may follow our research findings to reduce cost and improve quality. PMID- 22037594 TI - Classifying heterogeneity of spontaneous up-states: a method for revealing variations in firing probability, engaged neurons and Fano factor. AB - The dynamics of spontaneous and sensory-evoked up-states have been recently compared, in multi-site recordings in vivo and found to have similarities and differences. Also in vitro, this is evident because we here describe a novel computational method to classify into statistically different states the spontaneous reverberating activity recorded from long-term (12-18 days-in vitro) cultured cortical neurons (from 60-site multi-electrode arrays, MEA). State classification was performed by spike number time histograms (SNTH, or other burst features) of excitatory and inhibitory neuron clusters and revealed that in novel identified states the number of engaged neurons or up-state duration can change. To improve the characterization of each state we also computed the firing spike histograms (FSH) which revealed a new facet of the firing probability of clusters. In exemplary functional experiments we show that: (i) up to 6-7 states can be safely categorized during several hours of recordings without observing spike rate changes, (ii) they disappear after a short pharmacological stimulation being replaced with novel states active and living up to 6-8 h, (iii) antagonists in the nM range can split the activity of a homogeneous network into the chronological coexistence of 2 states, one completely different and one not significantly different from control state. In conclusion, we believe that this novel procedure better characterizes the number of functional states of a network and opens up the possibility of predicting the elementary "vocabulary" used by small networks of neurons. PMID- 22037595 TI - Performance comparison of extracellular spike sorting algorithms for single channel recordings. AB - Proper classification of action potentials from extracellular recordings is essential for making an accurate study of neuronal behavior. Many spike sorting algorithms have been presented in the technical literature. However, no comparative analysis has hitherto been performed. In our study, three widely-used publicly-available spike sorting algorithms (WaveClus, KlustaKwik, OSort) were compared with regard to their parameter settings. The algorithms were evaluated using 112 artificial signals (publicly available online) with 2-9 different neurons and varying noise levels between 0.00 and 0.60. An optimization technique based on Adjusted Mutual Information was employed to find near-optimal parameter settings for a given artificial signal and algorithm. All three algorithms performed significantly better (p<0.01) with optimized parameters than with the default ones. WaveClus was the most accurate spike sorting algorithm, receiving the best evaluation score for 60% of all signals. OSort operated at almost five times the speed of the other algorithms. In terms of accuracy, OSort performed significantly less well (p<0.01) than WaveClus for signals with a noise level in the range 0.15-0.30. KlustaKwik achieved similar scores to WaveClus for signals with low noise level 0.00-0.15 and was worse otherwise. In conclusion, none of the three compared algorithms was optimal in general. The accuracy of the algorithms depended on proper choice of the algorithm parameters and also on specific properties of the examined signal. PMID- 22037596 TI - Sources of stress for family members of nursing home residents with advanced dementia. AB - The sources of stress for families of nursing home (NH) residents with advanced dementia have not been well described. Semistructured interviews were conducted with 16 family members previously enrolled in the Choices, Attitudes, and Strategies for Care of Advanced Dementia at the End-of-Life study, a prospective cohort of 323 NH residents with advanced dementia and their family members. Questions were asked pertaining to the experience of having a family member in the NH, communication with health-care professionals, surrogate decision making, emotional distress, and recommendations for improvement in care. Transcripts were analyzed using the constant comparative method. The majority of the participants were women (63%), children of the resident (94%), and white (94%). The average age was 62 years. Four themes emerged: (1) inadequate resident personal care, resulting in family member vigilance and participation in care; (2) stress at the time of NH admission; (3) lack of communication with NH physicians; and (4) challenges of surrogate decision making, including the need for education to support advance care planning and end-of-life decisions. Our results support the provision of emotional support to families upon resident admission, education regarding prognosis to guide decision making, improved resident care, and greater communication with health care professionals. PMID- 22037597 TI - The influence of chronic stress on dementia-related diagnostic change in older adults. AB - Increased susceptibility of the aging brain to both chronic stress and incipient dementia-related neuropathology may accelerate cognitive decline. We investigated associations between chronic stress and diagnostic change in 62 individuals (mean age, 78.7 y) participating in an Alzheimer disease research center longitudinal study. The subjects, diagnosed at baseline as cognitively normal (CN) or with mild cognitive impairment (MCI), were followed for an average of 2.5 years. Senior neurologists, blind to detailed measures of stress and cognition, assigned diagnoses annually. Logistic regression analyses assessed the accuracy with which measures of stress (event-based ratings, cortisol levels) predicted the conversion to MCI and dementia. Eleven individuals with MCI at baseline received a dementia diagnosis during follow-up. Sixteen converted from cognitively normal to MCI. Prolonged, highly stressful experiences were associated with conversion from MCI to dementia. The cortisol awakening response, with age and education, was associated with a diagnostic change to MCI. Cortisol measures were not associated with the progression from MCI to dementia, and there was no association between stressful experiences and the change to MCI. Mechanisms associated with the transition from normal cognition to MCI may differ from those associated with a diagnostic change to dementia. These findings could facilitate the identification of interventional strategies to reduce the risk of decline at different stages of susceptibility. PMID- 22037598 TI - Agreement on diagnosis among patients, companions, and professionals after a dementia evaluation. AB - A diagnosis of dementia is challenging to deliver and to hear; yet, agreement on diagnosis is essential for effective treatment for dementia. We examined consensus on the results of an evaluation of dementia in 90 patients assessed at an Alzheimer's Disease Research Center. Diagnostic impressions were obtained from 5 sources: (1) the physician's chart; (2) the patient who was evaluated; (3) a companion present at the evaluation; (4) a diagnostic summary written by a nurse present during the evaluation; and (5) raters who watched a video of the diagnostic disclosure conversation. Overall, diagnostic consensus was only moderate. Patients and companions exhibited just fair agreement with one another. Agreement was better between physicians and companions compared with that between physicians and patients, although it was imperfect between physicians and video raters and the written summary. Agreement among sources varied by dementia severity, with the lowest agreement occurring in instances of very mild dementia. This study documents discrepancies that can arise in diagnostic communication, which could influence adjustment to a diagnosis of dementia and decisions regarding future planning and care. PMID- 22037599 TI - Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson Disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease. AB - BACKGROUND: We examined the utility of quantification of alpha-synuclein (SNCA) in the cerebrospinal fluid (CSF) to differentiate patients with Alzheimer disease (AD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA). METHODS: Thirty-seven patients were divided into 4 age matched and sex-matched clinical groups: AD (n = 9), DLB (n = 6), PD (n = 11), and MSA (n = 11). Eleven subjects served as neurological disease controls. The total of 48 subjects included 27 men and 21 women, aged 66.5 +/- 11.4 years. We performed a solid-phase sandwich enzyme-linked immunosorbent assay, which enables the sensitive quantification of CSF SNCA. RESULTS: In comparison with controls, CSF SNCA levels in AD were significantly higher (P < 0.05). CSF SNCA levels in PD (P < 0.001), DLB (P < 0.01), and MSA (P < 0.05) were all significantly lower than those in AD. However, CSF SNCA levels did not differ significantly among the 3 synucleinopathies. CONCLUSIONS: The results of the present study suggest that quantification of CSF SNCA helps in the differentiation of synucleinopathies (PD, DLB, and MSA) from AD. However, CSF SNCA levels did not differ significantly among the 3 synucleinopathies. PMID- 22037600 TI - The IkappaB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. AB - Toll-like receptor (TLR) signaling activates the inhibitor of transcription factor NF-kappaB (IkappaB) kinase (IKK) complex, which governs NF-kappaB-mediated transcription during inflammation. The RNase regnase-1 serves a critical role in preventing autoimmunity by controlling the stability of mRNAs that encode cytokines. Here we show that the IKK complex controlled the stability of mRNA for interleukin 6 (IL-6) by phosphorylating regnase-1 in response to stimulation via the IL-1 receptor (IL-1R) or TLR. Phosphorylated regnase-1 underwent ubiquitination and degradation. Regnase-1 was reexpressed in IL-1R- or TLR activated cells after a period of lower expression. Regnase-1 mRNA was negatively regulated by regnase-1 itself via a stem-loop region present in the regnase-1 3' untranslated region. Our data demonstrate that the IKK complex phosphorylates not only IkappaBalpha, thereby activating transcription, but also regnase-1, thereby releasing a 'brake' on IL-6 mRNA expression. PMID- 22037601 TI - Invariant natural killer T cells recognize lipid self antigen induced by microbial danger signals. AB - Invariant natural killer T cells (iNKT cells) have a prominent role during infection and other inflammatory processes, and these cells can be activated through their T cell antigen receptors by microbial lipid antigens. However, increasing evidence shows that they are also activated in situations in which foreign lipid antigens would not be present, which suggests a role for lipid self antigen. We found that an abundant endogenous lipid, beta-D glucopyranosylceramide (beta-GlcCer), was a potent iNKT cell self antigen in mouse and human and that its activity depended on the composition of the N-acyl chain. Furthermore, beta-GlcCer accumulated during infection and in response to Toll-like receptor agonists, contributing to iNKT cell activation. Thus, we propose that recognition of beta-GlcCer by the invariant T cell antigen receptor translates innate danger signals into iNKT cell activation. PMID- 22037602 TI - A platelet-mediated system for shuttling blood-borne bacteria to CD8alpha+ dendritic cells depends on glycoprotein GPIb and complement C3. AB - The acquisition of pathogen-derived antigen by dendritic cells (DCs) is a key event in the generation of cytotoxic CD8(+) T cell responses. In mice, the intracellular bacterium Listeria monocytogenes is directed from the blood to splenic CD8alpha(+) DCs. We report that L. monocytogenes rapidly associated with platelets in the bloodstream in a manner dependent on GPIb and complement C3. Platelet association targeted a small but immunologically important portion of L. monocytogenes to splenic CD8alpha(+) DCs, diverting bacteria from swift clearance by other, less immunogenic phagocytes. Thus, an effective balance is established between maintaining sterility of the circulation and induction of antibacterial immunity by DCs. Other gram-positive bacteria also were rapidly tagged by platelets, revealing a broadly active shuttling mechanism for systemic bacteria. PMID- 22037604 TI - Drosophila basement membrane collagen col4a1 mutations cause severe myopathy. AB - Recent data from clinical and mammalian genetic studies indicate that COL4A1 mutations manifest with basement membrane defects that result in muscle weakness, cramps, contractures, dystrophy and atrophy. In-depth studies of mutant COL4A1 associated muscle phenotype, however, are lacking and significant details of the muscle-specific pathomechanisms remain unknown. In this study, we have used a comprehensive set of Drosophila col4a1 and col4a2 mutants and a series of genetic and mutational analyses, gene, protein expression, and immunohistochemistry experiments in order to establish a Drosophila model and address some of these questions. The Drosophila genome contains two type IV collagen genes, col4a1 and col4a2. Mutant heterozygotes of either gene are viable and fertile, whereas homozygotes are lethal. In complementation analysis of all known mutants of the locus and a complementation matrix derived from these data we have identified the dominant lesions within the col4a1, but not within the col4a2 gene. Expression of a col4a1 transgene partially rescued the dominant and recessive mutant col4a1 alleles but not the col4a2 mutations that were all recessive. Partial complementation suggested that col4a1 gene mutations have strong antimorph effect likely due to the incorporation of the mutant protein into the triple helix. In col4a1 mutants, morphological changes of the oviduct muscle included severe myopathy with centronuclear myofibers leading to gradual development of female sterility. In larval body wall muscles ultrastructural changes included disturbance of A and I bands between persisting Z bands. In the most severely affected DTS-L3 mutant, we have identified four missense mutations within the coding region of the col4a1 gene two of which affected the Y within the Gly-X-Y unit and a 3' UTR point mutation. In conclusion, our Drosophila mutant series may serve as an effective model to uncover the mechanisms by which COL4A1 mutations result in compromised myofiber-basement membrane interactions and aberrant muscle function. PMID- 22037603 TI - Epigenetic repression of the Igk locus by STAT5-mediated recruitment of the histone methyltransferase Ezh2. AB - During B lymphopoiesis, recombination of the locus encoding the immunoglobulin kappa-chain complex (Igk) requires expression of the precursor to the B cell antigen receptor (pre-BCR) and escape from signaling via the interleukin 7 receptor (IL-7R). By activating the transcription factor STAT5, IL-7R signaling maintains proliferation and represses Igk germline transcription by unknown mechanisms. We demonstrate that a STAT5 tetramer bound the Igk intronic enhancer (E(kappai)), which led to recruitment of the histone methyltransferase Ezh2. Ezh2 marked trimethylation of histone H3 at Lys27 (H3K27me3) throughout the kappa chain joining region (J(kappa)) to the kappa-chain constant region (C(kappa)). In the absence of Ezh2, IL-7 failed to repress Igk germline transcription. H3K27me3 modifications were lost after termination of IL-7R-STAT5 signaling, and the transcription factor E2A bound E(kappai), which resulted in acquisition of H3K4me1 and acetylated histone H4 (H4Ac). Genome-wide analyses showed a STAT5 tetrameric binding motif associated with transcriptional repression. Our data demonstrate how IL-7R signaling represses Igk germline transcription and provide a general model for STAT5-mediated epigenetic transcriptional repression. PMID- 22037605 TI - An improved counterselection cassette for use in Haemophilus influenzae. AB - Counterselectable cassettes are extremely useful in molecular biology and allow for the creation of unmarked deletion mutants or the introduction of point mutations. I have constructed an inducible sacB cassette, using the tetracycline repressor. When used in tandem with a kanamycin-resistance marker, the cassette was successful in creating unmarked mutants in Haemophilus influenzae. The inducible nature of the cassette avoids some of the common problems associated with the utilization of sacB in counterselection. PMID- 22037606 TI - Characterization of heat shock protein 70 in the red claw crayfish (Cherax quadricarinatus): evidence for its role in regulating spermatogenesis. AB - Heat shock protein 70 (HSP70) is a member of molecular chaperones and is important for reproductive biological processes in eukaryotes. In this regard, a full length HSP70 comprised of 2366 nucleotides from the red claw crayfish Cherax quadricarinatus (CqHSP70) was characterized, which with an open-reading frame of 1959 bp encoded 652 amino acid residues. Its mRNA transcript expression in the testes was measured by real-time quantitative PCR. CqHSP70 mRNA transcripts were detected in all organs especially high in the testes. Furthermore, the greatest transcript levels were found during the spermatogonial preparation phase, while the lowest levels were found during the resting stage of the reproductive cycle. In addition, its distribution in the testes was determined by Western blot and immunohistochemistry. Western blot results revealed a single immunoreactive band with an estimated molecular mass of 70 kDa in different phases of testes development. The strongest immunolabeling positive signal was found in spermatogonia, with lower positive staining in secondary spermatocytes, and weak or absent level in the mature sperm. Interestingly, CqHSP70 was mainly located in the cytoplasm of sperm cells. Thus, our results indicate that CqHSP70 is an essential protein in spermatogenesis, with a crucial reproductive function during sperm maturation in invertebrates. PMID- 22037607 TI - Core promoter STRs: novel mechanism for inter-individual variation in gene expression in humans. AB - In a genome-scale analysis of the composition of core promoter sequences, we have recently shown that approximately 25% of the human protein-coding genes have at least one short tandem repeat (STR) of 3-repeats in their core promoters (i.e. the interval between -120 to +1). Through their nucleosome processing effect, GA repeats play a crucial role in the regulation of gene transcription. In this study, we chose the human SRY (sex determining region Y)-box 5 (SOX5) gene as a prototype of the GA-rich core promoters to investigate the role of core promoter GA-STRs in gene expression. The human SOX5 gene is indispensable for diverse embryonic developmental processes, ranging from oligodendrocyte development and corticogenesis to chondrogenesis, and regulation of the cell cycle. Whereas the absolute ratio of 99% of the genes range between 0.2 and 2, the composition of the core promoter of the two most ubiquitously expressed mRNAs of the human SOX5 gene (transcripts ID: ENST00000451604 and ENST00000309359) is exceptionally rich in purine nucleotides (purine/pyrimidine ratio: 61.5). Indeed, this core promoter is an island of four tandem GA-STRs, and lacks the known TATA and TATA-less elements for gene transcription. Evolutionary conservation of this region between human and mouse (75% homology) supports important functional role for this promoter. In this study, we show that this nucleotide composition is indeed a potent promoter (p<1*10(-10)), and different haplotypes across the region result in significant difference in gene expression (p<1*10(-6)). To our knowledge, this is the first report of functional STRs in a human gene core promoter. Based on our search on the core promoters of the entire human protein-coding genes annotated in the GeneCards database (19,927genes) for the presence of pure GA STRs, 429 genes contain at least one GA(3)-repeat in their core promoter. Core promoters with pure GA-STRs of GA(4) and above were observed in 61 genes. Our data unravel a novel mechanism for inter-individual variation in gene expression and complex traits/phenotypes through core promoter GA-STRs. PMID- 22037608 TI - Characterisation of the gene cluster for l-rhamnose catabolism in the yeast Scheffersomyces (Pichia) stipitis. AB - In Scheffersomyces (Pichia) stipitis and related fungal species the genes for L rhamnose catabolism RHA1, LRA2, LRA3 and LRA4 but not LADH are clustered. We find that located next to the cluster is a transcription factor, TRC1, which is conserved among related species. Our transcriptome analysis shows that all the catabolic genes and all genes of the cluster are up-regulated on L-rhamnose. Among genes that were also up-regulated on L-rhamnose were two transcription factors including the TRC1. In addition, in 16 out of the 32 analysed fungal species only RHA1, LRA2 and LRA3 are physically clustered. The clustering of RHA1, LRA3 and TRC1 is also conserved in species not closely related to S. stipitis. Since the LRA4 is often not part of the cluster and it has several paralogues in L-rhamnose utilising yeasts we analysed the function of one of the paralogues, LRA41 by heterologous expression and biochemical characterization. Lra41p has similar catalytic properties as the Lra4p but the transcript was not up-regulated on L-rhamnose. The RHA1, LRA2, LRA4 and LADH genes were previously characterised in S. stipitis. We expressed the L-rhamnonate dehydratase, Lra3p, in Saccharomyces cerevisiae, estimated the kinetic constants of the protein and showed that it indeed has activity with L-rhamnonate. PMID- 22037609 TI - Comparative expression analysis in mature gonads, liver and brain of turbot (Scophthalmus maximus) by cDNA-AFLPS. AB - Turbot is one of the most important farmed fish in Europe. This species exhibits a considerable sexual dimorphism in growth and sexual maturity that makes the all female production recommended for turbot farming. Our knowledge about the genetic basis of sex determination and the molecular regulation of gonad differentiation in this species is still limited. Our goal was to identify and compare gene expression and functions between testes and ovaries in adults in order to ascertain the relationship between the genes that could be involved in the gonad differentiation or related to the sex determination system. The identification of differentially expressed sex related genes is an initial step towards understanding the molecular mechanisms of gonad differentiation. For this, we carried out a transcriptome analysis based on cDNA-AFLP technique which allowed us to obtain an initial frame on sex-specific gene expression that will facilitate further analysis especially along the critical gonad differentiating period. With the aim of widening the study on sex-biased gene expression we reproduced the same experiments in two somatic tissues: liver and brain. We have selected the liver because it is the most analyzed one regarding sexual dimorphic gene expression and due to its importance in steroid hormones metabolism and the brain because the functional relationship between brain and gonad is documented. We found slight but important differences between sexes which deserve further investigation. PMID- 22037610 TI - Biochemistry and biology of the inducible multifunctional transcription factor TFII-I: 10 years later. AB - Exactly twenty years ago TFII-I was discovered as a biochemical entity that was able to bind to and function via a core promoter element called the Initiator (Inr). Since then several different properties of this signal-induced multifunctional factor were discovered. Here I update these ever expanding functions of TFII-I--focusing primarily on the last ten years since the first review appeared in this journal. PMID- 22037611 TI - Evolution of prokaryotic homologues of the eukaryotic SEFIR protein domain. AB - SEF/IL17 receptor (SEFIR) domains are mainly found in IL17 receptors (IL17Rs) and their adaptor proteins CIKS (connection to IKK and SAPK/JNK), which exert a host defense role in numbers of infectious diseases and promote inflammatory pathology in autoimmunity. Exploring the evolutionary pathway of SEFIR domains will provide further insight into their functions. Here, we have identified 84 SEFIR domain containing proteins from more than 1400 prokaryotic genomes. As most SEFIR domain containing bacterial genomes possess a single SEFIR encoding gene and the SEFIR protein domain forms homodimeric complexes like the Toll/IL1 receptor (TIR) domain, the single bacterial SEFIR proteins may receive binding partners from other organisms. Through comparative and phylogenetic sequence analyses, we show that bacterial SEFIR domain is more similar to that of vertebrate CIKS than IL17R, and it possibly emerges via a lateral gene transfer (LGT) from animals. In addition, our secondary and three-dimensional structural predictions of SEFIR domains reveal that human and pathogenic bacterial SEFIR domains share similar structural and electrostatic features. Our findings provide important clues for further experimental researches on determining the functions of SEFIR proteins in pathogenic prokaryotes. PMID- 22037612 TI - Convenient and mild synthesis of nitroarenes by metal-free nitration of arylboronic acids. AB - A novel methodology for the direct nitration of arylboronic acids has been developed. By using inexpensive tert-butyl nitrite various aromatic nitro compounds are produced in moderate to good yields (45-87%) without the need of any catalyst. PMID- 22037613 TI - First results from conservation studies of chlorophyllous spores of the Royal fern (Osmunda regalis, Osmundaceae). AB - Pteridophytes spore banks are a promising ex situ conservation tool used to increase the chances of survival of ferns, in fact that large quantities of germplasm with high genetic variation can be conserved in a small space with low economic and technical costs. However, methods to maintain the viability of chlorophyllous spores during storage are less understood. The aim of this study was to investigate the influence of long term storage on the viability of Royal Fern spores, which were stored under different conditions derived from various combinations of temperature and degrees of hydration. Survival and germination tests were performed after 1 and 28 months of storage. Our results showed the highest survival percentages for spores stored under Normal humidity at subzero temperatures (T=?-20 degrees C). These spores received no pre-treatment, dehydration, or cryoprotectants, which resulted in fast germination and gametophyte development which seemed to be stimulated by low temperatures. PMID- 22037614 TI - A comparison of approaches for estimating relative impacts of nonnative fishes. AB - Lack of standard methods for quantifying impact has hindered risk assessments of high-impact invaders. To understand methodological strengths and weaknesses, we compared five approaches (in parentheses) for quantifying impact of nonnative fishes: reviewing documented impacts in a large-scale database (review); surveying fish biologists regarding three categories of impact (socioeconomic, ecological, abundance); and estimating frequency of occurrence from existing collection records (collection). In addition, we compared game and nongame biologists' ratings of game and nongame species. Although mean species ratings were generally correlated among approaches, we documented important discrepancies. The review approach required little effort but often inaccurately estimated impact in our study region (Mid-Atlantic United States). Game fishes received lower ratings from the socioeconomic approach, which yielded the greatest consistency among respondents. The ecological approach exhibited lower respondent bias but was sensitive to pre-existing perceptions of high-impact invaders. The abundance approach provided the least-biased assessment of region specific impact but did not account for differences in per-capita effects among species. The collection approach required the most effort and did not provide reliable estimates of impact. Multiple approaches to assessing a species' impact are instructive, but impact ratings must be interpreted in the context of methodological strengths and weaknesses and key management issues. A combination of our ecological and abundance approaches may be most appropriate for assessing ecological impact, whereas our socioeconomic approach is more useful for understanding social dimensions. These approaches are readily transferrable to other regions and taxa; if refined, they can help standardize the assessment of impacts of nonnative species. PMID- 22037615 TI - Suitability analysis for greenway planning in China: an example of Chongming Island. AB - Suitability analysis for greenway planning was developed in the Western culture. When applying a suitability analysis to a very different sociocultural context such as China, it is necessary to identify what hinders or promotes it. Through an example of Chongming Island, this article demonstrates how to apply a suitability analysis for greenway planning in China. Furthermore, it argues that obstacles including a lack of data, peculiarity of capability scores within land use and a neglect of scientific group involvement are encountered in the process of applying suitability methods in Chongming or China. Early and sustained attention to such impediments could improve the success of suitability assessment in China. These research results are helpful for the planning and implementation of Chongming greenways. PMID- 22037616 TI - Estimating the cumulative ecological effect of local scale landscape changes in south Florida. AB - Ecosystem restoration in south Florida is a state and national priority centered on the Everglades wetlands. However, urban development pressures affect the restoration potential and remaining habitat functions of the natural undeveloped areas. Land use (LU) planning often focuses at the local level, but a better understanding of the cumulative effects of small projects at the landscape level is needed to support ecosystem restoration and preservation. The South Florida Ecosystem Portfolio Model (SFL EPM) is a regional LU planning tool developed to help stakeholders visualize LU scenario evaluation and improve communication about regional effects of LU decisions. One component of the SFL EPM is ecological value (EV), which is evaluated through modeled ecological criteria related to ecosystem services using metrics for (1) biodiversity potential, (2) threatened and endangered species, (3) rare and unique habitats, (4) landscape pattern and fragmentation, (5) water quality buffer potential, and (6) ecological restoration potential. In this article, we demonstrate the calculation of EV using two case studies: (1) assessing altered EV in the Biscayne Gateway area by comparing 2004 LU to potential LU in 2025 and 2050, and (2) the cumulative impact of adding limestone mines south of Miami. Our analyses spatially convey changing regional EV resulting from conversion of local natural and agricultural areas to urban, industrial, or extractive use. Different simulated local LU scenarios may result in different alterations in calculated regional EV. These case studies demonstrate methods that may facilitate evaluation of potential future LU patterns and incorporate EV into decision making. PMID- 22037617 TI - Evaluation of progress in achieving TMDL mandated nitrogen reductions in the Neuse River basin, North Carolina. AB - Management efforts to control excess algal growth in the Neuse River and Estuary, North Carolina began in the 1980s, with an initial focus on phosphorus (P) input reduction. However, continued water quality problems in the 1990s led to development of a Total Maximum Daily Load (TMDL) for nitrogen (N) in 1999 to improve conditions in N-sensitive estuarine waters. Evaluation of the effectiveness of management actions implemented in the Neuse River basin is a challenging endeavor due to natural variations in N export associated with climate. A simplified approach is presented that allows evaluation of trends in flow-normalized nutrient loading to provide feedback on effectiveness of implemented actions to reduce N loading to estuarine waters. The approach is applied to five watershed locations, including the headwaters of the Neuse Estuary. Decreases in nitrate + nitrite (NO(3)-N) concentrations occurred throughout the basin and were largest just downstream of the Raleigh metropolitan area. Conversely, concentrations of total Kjeldahl N (TKN) increased at many stations, particularly under high flow conditions. This indicates a relative increase in organic N (Org-N) inputs since the mid-1990s. Overall, patterns in different N fractions at watershed stations indicate both partial success in reducing N inputs and ongoing challenges for N loading under high flow conditions. In downstream waters, NO(3)-N concentrations decreased concurrent with TMDL implementation in the upper portion of the estuary but not in the middle and lower reaches. The lack of progress in the middle and lower reaches of the estuary may, at least in part, be affected by remineralization of settled particle-bound N deposited under high river flows. PMID- 22037618 TI - Livelihood sustainability and community based co-management of forest resources in China: changes and improvement. AB - Community-based co-management (CBCM) has been applied in some communities near natural reserves in China. This paper uses Gansu Baishuijiang National Natural Reserve in China as a case study for livelihood improvements under CBCM projects. We demonstrate change from 2006 to 2010 in five classes of livelihood capital (social, human, natural, physical and financial capitals), illustrating the effectiveness of CBCM projects. Specifically, there are increases in mean family income and improvements in forest conservation. However, some problems in the design and implementation of CBCM projects remain, including the complicated social and political relationship between government and community, social exclusion and uneven application of benefits within communities, and the lack of integration of indigenous cultures and traditional beliefs. Attention for special groups in community and improving the design of CBCM Projects. Study shows that under the cooperation of government, CBCM projects and local community residents, the harmonious development of sustainable livelihood improvement and forest resources conservation will be an important trend in the future. PMID- 22037619 TI - Protection of porcine islet xenografts in mice using sertoli cells and monoclonal antibodies. AB - BACKGROUND: To remedy the shortage of human donor islets, xenotransplantation of neonatal porcine islets (NPI) provides an attractive alternative source of donor tissue so long as graft rejection can be circumvented. Thus, in this study, we sought to determine whether cotransplantation of NPI with Sertoli cells (SC) combined with a short-course treatment of monoclonal antibody (mAb) could provide long-term islet xenograft survival. METHODS: NPI alone or NPI cotransplanted with neonatal porcine SC were transplanted into diabetic C57BL/6 mice. These mice were left untreated or were treated with a short course of antileukocyte function associated antigen-1 (LFA-1), anti-CD154, or anti-CD45RB mAb. Blood glucose levels were monitored twice a week to assess graft function. At more than 100 days posttransplantation or on the day of rejection, graft-bearing kidneys were collected for characterization using immunohistochemistry. RESULTS: None of the untreated control mice transplanted with NPI alone (0/5) or NPI cotransplanted with SC (0/8) achieved normoglycemia. However, of the mice receiving NPI alone, 3 of 7 treated with anti-LFA-1 mAb, 2 of 7 treated with anti-CD154 mAb, and 1 of 7 treated with anti-CD45RB mAb achieved long-term graft survival (>100 days). These proportions improved considerably when NPI were cotransplanted with SC, as 15 of 15 mice treated with anti-LFA-1 mAb, 7 of 8 mice treated with anti-CD154 mAb, and 4 of 9 mice treated with anti-CD45RB mAb achieved long-term graft survival. CONCLUSIONS: These results show that transient administration of anti-LFA-1 mAb or anti-CD154 mAb is efficacious in prolonging NPI xenograft survival when islets are cotransplanted with SC. Interleukin-4 and Serpina3n may be important mediators of protection observed in this model. PMID- 22037620 TI - [Intramedullary nailing of proximal tibia fractures]. AB - OBJECTIVE: Restoration of axis, length, and rotation of the lower leg. Sufficient primary stability of the osteosynthesis for early functional aftercare. Maintaining mobility of knee joint. Bone healing in closed and open fractures. INDICATIONS: Closed and open isolated proximal tibia and lower leg fractures (AO 42). Extraarticular fractures of the proximal tibia (AO 41 A2/A3). Intraarticular fractures of the proximal tibia (AO 41 C1/C2) in combination with other implants. Segmental tibia fractures (AO 42 C1/C2) with short proximal fragment. Comminuted tibia shaft fractures (AO 42 C3) with short proximal fragment. CONTRAINDICATIONS: Very poor general condition (e.g., bedridden). Flexion of knee less than 90 degrees . Infection in the nail's and bolt's insertion area. Infection of the tibia intramedullary canal. Complex fractures of the tibia plateau (AO 41 C3). Open physis. SURGICAL TECHNIQUE: Closed reduction of the fracture. If necessary, use of reduction clamps through additional stab incisions or open surgical procedures. In some cases, additional osteosynthesis procedures are necessary (e.g., compression screws). Positioning of the patient on a radiolucent table or a traction table. Opening of the proximal tibia in line with the medullary canal. Cannulated or noncannulated insertion of the nail with or without reaming of the medullary canal. Control of axis, length, and rotation of the lower leg. Triple proximal interlocking in three different planes with the targeting device. Double distal interlocking. POSTOPERATIVE MANAGEMENT: Immediate mobilization of the knee joint. Depending on the type of fracture, mobilization with 20 kg partial weight bearing or pain-dependent full weight bearing with crutches. X-ray controls after 3, 6, and 12 weeks and increase of weight bearing depending on the fracture status. RESULTS: In a prospective multicenter study on the stabilization of tibia fractures with the Expert Tibial Nail, 22 patients with proximal third tibia fractures were documented. Seventeen patients could be reviewed clinically and radiologically after 1 year. A non-union was registered in 1 patient (5.9%), a malalignment in any plane above 5 degrees in 3 fractures (17.6%). PMID- 22037621 TI - [Elastic stable intramedullary nailing after corrective osteotomy of symptomatic malunited midshaft clavicular fractures]. AB - OBJECTIVE: To restore alignment and length of the clavicle, to relieve typical symptoms of malunion, and to improve functional outcome and aesthetic results. INDICATIONS: Symptomatic malunion after clavicular fractures, including local pain and tenderness, weakness and rapid fatigability of the shoulder girdle muscles, impairment of overhead mobility, numbness, parasthesia, and pain of the arm and fingers during overhead movements due to brachial plexus irritation (thoracic outlet syndrome), and dissatisfaction with the appearance of the shoulder girdle. CONTRAINDICATIONS: Atrophic nonunions, osteoporosis, asymptomatic malunion. SURGICAL TECHNIQUE: A 5-cm skin incision is made above the deformity of the malunited clavicle. The osteotomy plane is determined under fluoroscopic guidance, within the callus separating the two original main fracture fragments. Under fluoroscopic guidance, the medullary canal is reopened on both sides with a 2.7 mm drill bit. Afterwards a 1.5 cm skin incision is made just above the sternal end of the clavicle. The anterior cortex is drilled and a titanium nail (diameter 2.5 mm) is introduced. Under rotational movement, the nail is advanced to the osteotomy site. The nail is inserted into the lateral fragment. Then the inserted nail is cut back as far as possible on the medial entry point. Wound closure. POSTOPERATIVE MANAGEMENT: No immobilization, movement not restricted. Patients are encouraged to use the arm in daily activities. Heavy weight bearing is not allowed until osseus consolidation. RESULTS: In 5 patients (3 men, 2 women) with a mean age of 34 years (range, 23-44 years) with symptomatic malunion after clavicular fractures, a corrective osteotomy and elastic stable intramedullary nailing (ESIN) was performed. After 6 months (mean 4.4 months), all osteotomies were healed and the nails were removed. There were no complications. At final follow-up (12 months), the DASH and Constant scores were significantly improved compared to preoperative values. Patients were significantly more satisfied with the appearance of the shoulder girdle and overall outcome. PMID- 22037622 TI - [Stabilization of inter- and subtrochanteric femoral fractures with the PFNAlpha(r)]. AB - OBJECTIVE: Intramedullary nail system fixation of inter- and subtrochanteric femoral fractures allows early weight-bearing, especially in osteoporotic bone. Restoration of anatomical shape and early return to function of the injured leg. INDICATIONS: All inter- and subtrochanteric fractures of AO type 31-A without limitation. CONTRAINDICATIONS: Open physes and unsuitable femoral shaft anatomy (increased anterior bow of femoral shaft or malunion after femoral fracture). SURGICAL TECHNIQUE: If possible closed, otherwise open fracture reduction on a fracture table and unreamed intramedullary nailing. Fixation of the fracture by insertion of a helical blade via a guide wire in the head-neck fragment of the femur. Option of static or dynamic locking at the femoral diaphysis. POSTOPERATIVE MANAGEMENT: Early mobilization immediately the day after surgery with full weight-bearing and use of assistive device, as tolerated. Thrombosis prophylaxis for 6 weeks with fondaparinux, rivaroxaban or a low molecular weight heparin (LMWH), alternatively oral anticoagulation. RESULTS: Between April 2004 and June 2005, the AO multicenter study at 11 European trauma centers included 313 patients (mean age 80.6 years, 77% women, 23% men) with 315 unstable trochanteric fractures treated with a Peroximal Femoral Nail Antirotation(r) (PFNAlpha(r)) device for consecutive follow-up [24]. In 82%, the fractures were 31-A2, while in 18% the fractures were 31-A3. Average operation time for A2 fractures was 56 min and 66 min for A3 fractures. Average duration of hospital stay in the trauma center was 12 days. Surgical reduction and fracture fixation that permitted full weight-bearing immediately after operation was achieved in 72% of cases. Of 165 complications, 46 were surgery-related with unplanned revision surgery in 28 cases (including 7 femur fractures and 4 acetabular penetrations). Follow-up for more than 1 year was possible in 56% of patients. After 1 year, 89% of the fractures were consolidated. The highest complication rate was found in fractures type 31-A2.3 and in patients older than 90 years. The recorded number of implant-related complications (14.6%) is comparable to the results of other intramedullary and extramedullary implants. PMID- 22037623 TI - Gold and iron oxide hybrid nanocomposite materials. AB - This critical review provides an overview of current research activities that focused on the synthesis and application of multi-functional gold and iron oxide (Au-Fe(x)O(y)) hybrid nanoparticles and nanocomposites. An introduction of synthetic strategies that have been developed for generating Au-Fe(x)O(y) nanocomposites with different nanostructures is presented. Surface functionalisation and bioconjugation of these hybrid nanoparticles and nanocomposites are also reviewed. A variety of applications such as theranostics, gene delivery, biosensing, cell sorting, bio-separation, and catalysis is discussed and highlighted. Finally, future trends and perspectives of these sophisticated nanocomposites are outlined. Underpinning the fundamental requirements for effectively forming Au-Fe(x)O(y) hybrid nanocomposite materials would shed light on future development of nanotheranostics, nanomedicines, and chemical technologies. It would be interesting to investigate such multi component composite nanomaterials with different novel morphologies in the near future to advance chemistry, biology, medicine, and engineering multi disciplinary research (120 references). PMID- 22037624 TI - Potential role for alternatively activated macrophages in the secondary bacterial infection during recovery from influenza. AB - PURPOSE: Secondary bacterial infections are a common complication of influenza. Innate immune host defenses appear to be impaired following influenza, leading to susceptibility to subsequent bacterial infections. Alternatively activated macrophages (AAM) in the lungs may play a critical role in eliciting the hypersusceptibility to secondary bacterial pneumonia. METHODS: C57BL6 mice were challenged with sublethal doses of the mouse-adapted A/PR/8/34 (PR8) influenza virus or saline and allowed to recover. At complete recovery (day 14), mice were re-challenged with sublethal doses of Streptococcus pneumoniae serotype 3 (Sp3). RESULTS: PR8-recovered mice developed a rapidly fatal pulmonary infection to a 100-fold sublethal pneumococcal challenge, whereas PR8-naive mice demonstrated no mortality or illness. The cytokines which induce AAM (IL-4 and IL-13) and the expression of genes associated with AAM (Arginase-1, FIZZ1, and YM1) were elevated after PR8 infection. Flow cytometry suggests that alveolar macrophages demonstrate the AAM-phenotype, as indicated by MGL-1 and MHCII expression, in response to PR8 infection. Recovery from PR8 was associated with blunted cytokine responses to TLR ligands. CONCLUSIONS: The mechanisms of immune regulation during recovery from influenza are being elucidated. We provide evidence that pulmonary AAM are induced during influenza infection and may contribute to the elicitation of hypersusceptibility to a secondary bacterial infection. PMID- 22037625 TI - Expression of bleomycin hydrolase in keratinization disorders. AB - A neutral cysteine protease, bleomycin hydrolase (BH), is widely expressed in mammalian tissues, with the skin seeming to contain the highest level. Our previous study revealed that BH transcription is modulated both during differentiation and by cytokines. However, BH involvement in keratinization disorder is not well known. In the present study, we performed immunohistochemical studies of BH and other serine/cysteine proteases in human normal skin and lesional skin with keratinization disorders. BH-positive cells were detected in granular layers of orthokeratotic and hyperkeratotic skin diseases, such as erythrokeratoderma and lichen planus. In parakeratotic skin diseases with porokeratosis, pityriasis rubra pilaris and psoriasis, BH staining was decreased in lesional skins compared to that in normal skin. Similar results were obtained for cysteine proteases, caspase-14 and calpain I. On the other hand, cells positive for serine proteases kallikrein 5 and 7 were increased in parakeratotic and inflammatory skin diseases, such as psoriasis. Semi quantification analysis revealed that BH- and caspase-14-positive staining had higher intensity than those of the other proteases in normal epidermis. As BH is the major citrulline aminopeptidase in normal granular layer, the alternation would have a significant effect on terminal differentiation processes, such as aberrant processing of deiminated peptides. Therefore, BH may play an important role during the late stage of epidermal differentiation. PMID- 22037626 TI - Osteopontin, a protein with cytokine-like properties: a possible involvement in pemphigus vulgaris. AB - Pemphigus is an autoimmune blistering disease characterized by severe and chronic course, histopathologically characterized by infiltration of a large quantity of eosinophils, neutrophils, and activated Th1 and Th2 cells around the blister. Polarization of Th cells to Th1 or Th2 phenotypes, a critical aspect of cell mediated immunity, is influenced by production of early cytokines, including osteopontin. To determine the involvement of osteopontin in pemphigus vulgaris patients in active stage of the disease, auto-antibodies to desmoglein-1 and desmoglein-3 and plasmatic osteopontin levels were examined by ELISA tests. In this work, significant plasmatic level of osteopontin in PV patients with active stage of disease were found particularly in those patients with both skin and oral pemphigus. OPN might drive the immune responses playing an important role in pemphigus onset. PMID- 22037627 TI - A putative in vitro organotypic model of molting with human skin explants. AB - We report finding a simple method to partially reproduce the characteristic process of molting that takes place in invertebrates using human skin explants in vitro. In this method, human skin explants discarded from regular plastic surgery procedures were kept, submersed, in regular growth medium for 10 days at 4 degrees C. After that period, the skin explants were cultured at the air-liquid interface for another 10 days. Histological analysis of the skin revealed the formation of one full epidermal structure and an additional intermediate epidermal structure containing a putative stratum corneum, superimposed one of top of the other, in which we consider an equivalent model of "molting" or "ecdysis". Basic analysis of cell proliferation and differentiation of the explants at different stages of the process are briefly presented. We believe this model can be used in the study of certain human skin diseases as well as in comparative animal physiology. PMID- 22037628 TI - Chromosome recombination. PMID- 22037629 TI - Assessing the endosulfan contamination in an unconfined aquifer. AB - Groundwater samples were analyzed in order to elucidate the fate of endosulfan in the soil and its release mechanism into water of an unconfined aquifer. Residual alfa endosulfan was determined in all the wells; however, beta endosulfan was below 0.001 MUg/L. Maximum adsorption rates of alfa and beta endosulfan were 91% 86% on the topsoil; 87%-91% on the subsoil, respectively. About 13%-23% desorption rate on the topsoil and subsoil exhibited the probability of endosulfan movement in the soil. The study showed that a hydrophobic-moderately persistent pesticide can reach to groundwater despite the high clay content of soil. PMID- 22037630 TI - Presence of polycyclic aromatic hydrocarbons (PAHs) in top soils from rural terrains in Mexico City. AB - A soil survey was carried out to determine the levels and sources and concentrations of 16 polycyclic aromatic hydrocarbons in 2 semi-rural terrains in Mexico City (Tlahuac and Milpa Alta) during 2008-2009. PAH determination was made by Soxhlet extraction and chromatographic clean-up with final analysis by gas chromatography with a flame ionization detector. The concentrations in Tlahuac were 9.13 mg/kg (dry season) and 11.22 mg/kg (wet season) and in Milpa Alta were 11.43 mg/kg (dry season) and 35.77 mg/kg (wet season). The variation of total PAH concentrations are due to environmental and anthropogenic conditions within Mexico City and also the addition of compost to the soils. According to Mexican regulations BaP, DaA, BbF and Ind were within the permissible limit (2 mg/kg) for agricultural and residential soils and BkF was close to the limit (8 mg/kg). The total PAH concentrations do however surpass the permissible European limit of 1,000 MUg/kg and there is probably some risk to human health, in spite of measures aimed at decreasing contamination in Mexico City. Long term monitoring of soils will be necessary. PMID- 22037631 TI - Environmental fate of polyhexamethylene biguanide. AB - Polyhexamethylene biguanide (PHMB) is used as a bacteriocidal agent in a variety of applications from medical devices to pools, but is highly toxic to some aquatic species. The stability of PHMB in various environmental matrices was examined. 80% of PHMB was present in fortified creek samples after 20 days, but bound immediately to soils with the exception of sandy soil. PHMB was absorbed to below detectable levels by weathered concrete within 12 h. In addition, one over the counter wound care product containing PHMB was evaluated to assess environmental leaching; detectable levels (20 MUg/mL) were still present after 1 week. PMID- 22037632 TI - Mercury and cadmium contamination in traffic soil of Beijing, China. AB - The concentrations of mercury and cadmium in surface soil along the three ring road with high traffic density from Beijing, China, were investigated. The concentrations of cadmium and mercury in urban soils were in the range of 0.086 1.59 and 0.16-3.68 mg kg(-1), which exceeded the upper limits of potential toxic elements concentration for agricultural soils of China (PTE-MPC). The metal elements of cadmium and mercury showed similar spatial distribution and seasonal variations. Concentrations of cadmium and mercury in surface soil along the three ring road were significantly higher than previous reported values, which was attributed to the increased traffic density in Beijing. Results from this study demonstrated that the soil of the three ring road had endured severe cadmium and mercury pollution. PMID- 22037633 TI - Flexible ureterorenoscopy versus miniaturized PNL for solitary renal calculi of 10-30 mm size. AB - INTRODUCTION: The value of flexible ureterorenoscopy (fURS) and miniaturized PNL (mPNL) for larger renal calculi is under discussion. This non-randomized prospective study aimed to evaluate fURS and mPNL for solitary renal stones of 10 30 mm size. MATERIALS AND METHODS: fURS was carried out in 21 patients with last generation 7.5F endoscopes. Ureteral access sheaths were used in 19 patients. For mPNL, an 18F modified Amplatz sheath with a 14F nephroscope were used (n = 25). The procedure was performed either tubeless with an antegrade stent or a nephrostomy. Outcome and complications of both procedures were assessed. RESULTS: Patients' demographics and stone sizes were comparable (18 +/- 5 vs. 19 +/- 4 mm, P = 0.08). Patients in the fURS group had a higher mean BMI (31 vs. 27, P < 0.05). Total OR time was significantly longer for fURS (106 +/- 51 vs. 59 +/- 19 min., P < 0.001). More patients were stone-free after one single percutaneous treatment, while 2nd-stage treatments with fURS were common (total procedures 1.04 vs. 1.52, P < 0.001; immediate stone-free rate (SFR) 96% vs. 71.5%, P < 0.001). SFR after 4 weeks was 100% (mPNL) and 85.8% (fURS) (P < 0.01). Minor complications as classified by Clavien I or II occurred in 16 and 23.8%, mPNL and fURS, respectively, P = 0.13). No major complications (Clavien III-V) occured in both groups. CONCLUSIONS: Our series supports both the concept of either percutaneous or retrograde endoscopic treatment for renal calculi with both modalities offering excellent safety. However, while for fURS, a significantly higher rate of 2nd-stage procedures was necessary, and mPNL led to faster and higher SFR without increasing complication rate. PMID- 22037634 TI - Impact of ureteral stenting prior to ureterorenoscopy on stone-free rates and complications. AB - OBJECTIVE: To date, only few studies have evaluated the impact of ureteral stenting prior to ureterorenoscopy. This study is to clarify the role of preoperative ureteral stenting in the treatment for ureteral stones. METHODS: We retrospectively reviewed 550 ureterorenoscopies from 1998 to 2008. Patients were classified into two groups depending on whether they had a stent placed before URS. Baseline characteristics of patients and stone properties, stone-free rates, complications, and operation times were compared between both groups. Subanalysis was performed regarding stone localization. We retrospectively reviewed data from patient documentation, X-ray imagery, intravenous urography, and operation reports. RESULTS: Baseline characteristics of patients were similar in both groups. The majority of patients underwent stent placement before the ureteroscopic stone treatment (88.4%). The mean operation time in the prestented group was longer (43.3 vs. 38.4 min). Stone-free rate of patients with stent was 72.2%, compared to 59.4% without preoperative stenting. The rate of minor complications was 4.7% with stent versus 9.4% without stent, major complications 0.6% versus 1.6%, respectively. Patients with distal ureter stones had similar stone-free rates regardless of a stent placement (90.1% with stent vs. 87.6% without), and no difference in complication rates was observed (3.5% with stent vs. 3.1% without), respectively. CONCLUSIONS: Stent placement prior to ureteroscopic stone treatment in distal ureter is not reasonable and does not considerably improve stone-free rates. PMID- 22037636 TI - April pain: aftermath of a colleague's suicide. PMID- 22037635 TI - Case scenario: opioid association with serotonin syndrome: implications to the practitioners. PMID- 22037637 TI - Simulation-based assessment of pediatric anesthesia skills. AB - BACKGROUND: Assessment of pediatric anesthesia trainees is complicated by the random nature of adverse patient events and the vagaries of clinical exposure. However, assessment is critical to improve patient safety. In previous studies, a multiple scenario assessment provided reliable and valid measures of the abilities of anesthesia residents. The purpose of this study was to develop a set of relevant simulated pediatric perioperative scenarios and to determine their effectiveness in the assessment of anesthesia residents and pediatric anesthesia fellows. METHODS: Ten simulation scenarios were designed to reflect situations encountered in perioperative pediatric anesthesia care. Anesthesiology residents and fellows consented to participate and were debriefed after each scenario. Two pediatric anesthesiologists scored each scenario by key action checklist. The psychometric properties (reliability, validity) of the scores were studied. RESULTS: Thirty-five anesthesiology residents and pediatric anesthesia fellows participated. The participants with greater experience administering pediatric anesthetics generally outperformed those with less experience. Score variance attributable to raters was low, yielding a high interrater reliability. CONCLUSIONS: A multiple-scenario, simulation-based assessment of pediatric perioperative care was designed and administered to residents and fellows. The scores obtained from the assessment indicated the content was relevant and that raters could reliably score the scenarios. Participants with more training achieved higher scores, but there was a wide range of ability among subjects. This method has the potential to contribute to pediatric anesthesia performance assessment, but additional measures of validity including correlations with more direct measures of clinical performance are needed to establish the utility of this approach. PMID- 22037638 TI - Lipid resuscitation of bupivacaine toxicity: long-chain triglyceride emulsion provides benefits over long- and medium-chain triglyceride emulsion. AB - BACKGROUND: The superiority of Intralipid, a long-chain triglyceride (LCT) emulsion versus Lipovenoes, a long- and medium-chain triglyceride (LCT/MCT) emulsion, in reversing local anesthetic-induced cardiac arrest is poorly defined and needs to be determined. METHODS: The study included two parts: in experiment A, bupivacaine (20 mg/kg) was injected to produce asystole. Either Intralipid 20% (LCT group, n = 30) or Lipovenoes 20% (LCT/MCT group, n = 30) with epinephrine was infused immediately. Return of spontaneous circulation and recurrence of asystole after resuscitation were recorded. In experiment B, 80 rats using the same model and resuscitation protocol were divided into 10 groups: LCT0, LCT15, LCT30, LCT60, and LCT120 and LCT/MCT0, LCT/MCT15, LCT/MCT30, LCT/MCT60, and LCT/MCT120 (n = 8 each; the subscripts represent respective observation period). LCT15-LCT120 and LCT/MCT15-LCT/MCT120 groups received Intralipid 20% or Lipovenoes 20%, respectively. Plasma and myocardial bupivacaine and triglyceride concentrations, as well as myocardial bioenergetics, were determined. RESULTS: In experiment A, 24 rats in LCT group and 23 in LCT/MCT group achieved return of spontaneous circulation (P = 0.754); among them, 2 (8.3%) and 8 (34.8%) rats suffered a repeated asystole, respectively (P = 0.027). In experiment B, plasma and myocardial bupivacaine concentrations in LCT15 and LCT60 groups were lower than LCT/MCT15 and LCT/MCT60 groups, respectively. Furthermore, the plasma bupivacaine level in LCT/MCT60 group was higher than LCT/MCT30 group (P = 0.003). CONCLUSIONS: LCT emulsion may be superior to LCT/MCT emulsion in treating bupivacaine-related cardiotoxicity as it was associated with fewer recurrences of asystole after resuscitation and lower myocardial bupivacaine concentrations. PMID- 22037639 TI - Metabotropic glutamate receptor 5 antagonism with fenobam: examination of analgesic tolerance and side effect profile in mice. AB - BACKGROUND: The metabotropic glutamate receptor 5 noncompetitive antagonist fenobam is analgesic in rodents. Future development of fenobam as an analgesic in humans will require a favorable long-term treatment profile and a lack of significant deleterious side effects. This study aimed to determine whether tolerance to fenobam's analgesic effects developed over 14 days and to assess for side effects in mice. METHODS: Mouse models of pain, locomotor behavior, and coordination were used. Fenobam or vehicle (n = 8 or 11 per group) was administered for 14 days, and analgesic tolerance to fenobam was assessed using the formalin test. Histopathologic examination, hematology, and clinical chemistry analysis after 14-day fenobam administration were also assessed (n = 12 or 9). The effects of fenobam on locomotor activity were assessed in the open field and elevated zero maze (n = 8 or 7). Coordination was assessed using ledge crossing and vertical pole descent tasks (n = 11 or 10). RESULTS: Tolerance to fenobam's analgesic effect did not develop after 14 days. Chronic fenobam administration resulted in statistically significantly less weight gain compared with vehicle control subjects, but did not cause any physiologically or statistically significant hematologic abnormalities, altered organ function, or abnormal histopathology of the liver, brain, or testes. Fenobam administration resulted in a metabotropic glutamate receptor 5-dependent increase in exploratory behavior but does not impair motor coordination at analgesic doses. CONCLUSIONS: Analgesic tolerance to repeat fenobam dosing does not develop. Chronic dosing of up to 14 days is well tolerated. Fenobam represents a promising candidate for the treatment of human pain conditions. PMID- 22037640 TI - Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3 glucuronide, are biologically active. AB - BACKGROUND: The long-lasting high-affinity opioid buprenorphine has complex pharmacology, including ceiling effects with respect to analgesia and respiratory depression. Plasma concentrations of the major buprenorphine metabolites norbuprenorphine, buprenorphine-3-glucuronide, and norbuprenorphine-3-glucuronide approximate or exceed those of the parent drug. Buprenorphine glucuronide metabolites pharmacology is undefined. This investigation determined binding and pharmacologic activity of the two glucuronide metabolites, and in comparison with buprenorphine and norbuprenorphine. METHODS: Competitive inhibition of radioligand binding to human MU, kappa, and delta opioid and nociceptin receptors was used to determine glucuronide binding affinities for these receptors. Common opiate effects were assessed in vivo in SwissWebster mice. Antinociception was assessed using a tail-flick assay, respiratory effects were measured using unrestrained whole-body plethysmography, and sedation was assessed by inhibition of locomotion measured by open-field testing. RESULTS: Buprenorphine-3 glucuronide had high affinity for human MU (Ki [inhibition constant] = 4.9 +/- 2.7 pM), delta (Ki = 270 +/- 0.4 nM), and nociceptin (Ki = 36 +/- 0.3 MUM) but not kappa receptors. Norbuprenorphine-3-glucuronide had affinity for human kappa (Ki = 300 +/- 0.5 nM) and nociceptin (Ki = 18 +/- 0.2 MUM) but not MU or delta receptors. At the dose tested, buprenorphine-3-glucuronide had a small antinociceptive effect. Neither glucuronide had significant effects on respiratory rate, but norbuprenorphine-3-glucuronide decreased tidal volume. Norbuprenorphine-3-glucuronide also caused sedation. CONCLUSIONS: Both glucuronide metabolites of buprenorphine are biologically active at doses relevant to metabolite exposures, which occur after buprenorphine. Activity of the glucuronides may contribute to the overall pharmacology of buprenorphine. PMID- 22037641 TI - Perioperative pharmacokinetics of methadone in adolescents. AB - BACKGROUND: Methadone is frequently administered to adults experiencing anesthesia and receiving pain treatment. Methadone pharmacokinetics in adults are well characterized, including the perioperative period. Methadone is also used in children. There is, however, no information on methadone pharmacokinetics in children of any age. The purpose of this investigation was to determine the pharmacokinetics of intravenous methadone in children undergoing surgery. Perioperative opioid-sparing effects were also assessed. METHODS: Eligible subjects were children 5-18 yr undergoing general anesthesia and surgery, with an anticipated postoperative inpatient stay exceeding 3 days. Three groups of 10 to 11 patients each received intravenous methadone hydrochloride after anesthetic induction in ascending dose groups of 0.1, 0.2, and 0.3 mg/kg (up to 20 mg). Anesthetic care was not otherwise changed. Venous blood was obtained for 4 days, for stereoselective determination of methadone and metabolites. Pain assessments were made each morning. Daily and total opioid consumption was determined. Perioperative opioid consumption and pain was determined in a second cohort, which was matched to age, sex, race, ethnicity, surgical procedure, and length of stay, but not receiving methadone. RESULTS: The final methadone study cohort was 31 adolescents (14 +/- 2 yr, range 10-18) undergoing major spine surgery for a diagnosis of scoliosis. Methadone pharmacokinetics were linear over the dose range 0.1-0.3 mg/kg. Disposition was stereoselective. Methadone administration did not dose-dependently affect postoperative pain scores, and did not dose dependently decrease daily or total postoperative opioid consumption in spinal fusion patients. CONCLUSIONS: Methadone enantiomer disposition in adolescents undergoing surgery was similar to that in healthy adults. PMID- 22037643 TI - Microfabricated multiple field of view imaging flow cytometry. AB - The combination of microscopy and flow cytometry enables image based screening of large collections of cells. Despite the proposition more than thirty years ago, adding high resolution wide-field imaging to flow cytometers remains challenging. The velocity of cells in flow cytometry can surpass a meter per second, requiring either sub-microsecond exposure times or other sophisticated photodetection techniques. Instead of faster detectors and brighter sources, we demonstrate that by imaging multiple channels simultaneously, a high throughput can be maintained with a flow velocity reduced in proportion to the degree of parallelization. The multi-field of view imaging flow cytometer (MIFC) is implemented with parallel arrays of microfluidic channels and diffractive lenses that produce sixteen wide field images with a magnification of 45 and submicron resolution. Using this device, we have imaged latex beads, red blood cells, and acute myeloid leukemia cells at rates of 2,000-20,000 per second. PMID- 22037642 TI - Relationship between bispectral index values and volatile anesthetic concentrations during the maintenance phase of anesthesia in the B-Unaware trial. AB - BACKGROUND: Hypnotic depth during anesthesia affects electroencephalography waveforms and electroencephalogram-derived indices, such as the bispectral index (BIS). Titrating anesthetic administration against the BIS assumes reliable relationships between BIS values, electroencephalogram waveforms, and effect site concentration, beyond loss of responsiveness. Associations among BIS, end-tidal anesthetic concentrations (ETAC), and patient characteristics were examined during anesthetic maintenance, using B-Unaware trial data. METHODS: Pharmacokinetically stable ETAC epochs during intraoperative anesthetic maintenance were analyzed. A generalized estimating equation determined independent relationships among BIS, ETAC (in age-adjusted minimum alveolar concentration equivalents), patient characteristics, and 1-yr mortality. Further individual and population characteristics were explored graphically. RESULTS: A total of 3,347,523 data points from 1,100 patients were analyzed over an ETAC range from 0.42 to 1.51 age-adjusted minimum alveolar concentration. A generalized estimating equation yielded a best predictive equation: BIS = 62.9 1.6 (if age younger than 60 yr) -1.6 (if female) -2.5 (if American Society of Anesthesiologists physical status more than 3) -2.6 (if deceased at 1 yr) -2.5 (if N2O was not used) -1.4 (if midazolam dose more than 2 mg) -1.3 (if opioid dose more than 50 morphine equivalents) -15.4 * age-adjusted minimum alveolar concentration. Although a population relationship between ETAC and BIS was apparent, interindividual variability in the strength and reliability of this relationship was large. Decreases in BIS with increasing ETAC were not reliably observed. Individual-patient linear regression yielded a median slope of -8 BIS/1 age-adjusted minimum alveolar concentration (interquartile range -30, 0) and a median correlation coefficient of -0.16 (interquartile range -0.031, -0.50). CONCLUSIONS: Independent of pharmacokinetic confounding, BIS frequently correlates poorly with ETAC, is often insensitive to clinically significant changes in ETAC, and is vulnerable to interindividual variability. BIS is therefore incapable of finely guiding volatile anesthetic titration during anesthetic maintenance. PMID- 22037644 TI - Metabolic network analysis of perfused livers under fed and fasted states: incorporating thermodynamic and futile-cycle-associated regulatory constraints. AB - Isolated liver perfusion systems have been extensively used to characterize intrinsic metabolic changes in liver under various conditions, including systemic injury, hepatotoxin exposure, and warm ischemia. Most of these studies were performed utilizing fasted animals prior to perfusion so that a simplified metabolic network could be used in order to determine intracellular fluxes. However, fasting induced metabolic alterations might interfere with disease related changes. Therefore, there is a need to develop a "unified" metabolic flux analysis approach that could be similarly applied to both fed and fasted states. In this study we explored a methodology based on elementary mode analysis in order to determine intracellular fluxes and active pathways simultaneously. In order to decrease the solution space, thermodynamic constraints, and enzymatic regulatory properties for the formation of futile cycles were further considered in the model, resulting in a mixed integer quadratic programming problem. Given the published experimental observations describing the perfused livers under fed and fasted states, the proposed approach successfully determined that gluconeogenesis, glycogenolysis and fatty acid oxidation were active in both states. However, fasting increased the fluxes in gluconeogenic reactions whereas it decreased fluxes associated with glycogenolysis, TCA cycle, fatty acid oxidation and electron transport reactions. This analysis further identified that more pathways were found to be active in fed state while their weight values were relatively lower compared to fasted state. Glucose, lactate, glutamine, glutamate and ketone bodies were also found to be important external metabolites whose extracellular fluxes should be used in the hepatic metabolic network analysis. In conclusion, the mathematical formulation explored in this study is an attractive tool to analyze the metabolic network of perfused livers under various disease conditions. This approach could be simultaneously applied to both fasted and fed data sets. PMID- 22037645 TI - Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. AB - Exercise, obesity and type 2 diabetes are associated with elevated plasma concentrations of interleukin-6 (IL-6). Glucagon-like peptide-1 (GLP-1) is a hormone that induces insulin secretion. Here we show that administration of IL-6 or elevated IL-6 concentrations in response to exercise stimulate GLP-1 secretion from intestinal L cells and pancreatic alpha cells, improving insulin secretion and glycemia. IL-6 increased GLP-1 production from alpha cells through increased proglucagon (which is encoded by GCG) and prohormone convertase 1/3 expression. In models of type 2 diabetes, the beneficial effects of IL-6 were maintained, and IL-6 neutralization resulted in further elevation of glycemia and reduced pancreatic GLP-1. Hence, IL-6 mediates crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand. This previously unidentified endocrine loop implicates IL-6 in the regulation of insulin secretion and suggests that drugs modulating this loop may be useful in type 2 diabetes. PMID- 22037646 TI - Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. AB - Intra-abdominal tumors, such as ovarian cancer, have a clear predilection for metastasis to the omentum, an organ primarily composed of adipocytes. Currently, it is unclear why tumor cells preferentially home to and proliferate in the omentum, yet omental metastases typically represent the largest tumor in the abdominal cavities of women with ovarian cancer. We show here that primary human omental adipocytes promote homing, migration and invasion of ovarian cancer cells, and that adipokines including interleukin-8 (IL-8) mediate these activities. Adipocyte-ovarian cancer cell coculture led to the direct transfer of lipids from adipocytes to ovarian cancer cells and promoted in vitro and in vivo tumor growth. Furthermore, coculture induced lipolysis in adipocytes and beta oxidation in cancer cells, suggesting adipocytes act as an energy source for the cancer cells. A protein array identified upregulation of fatty acid-binding protein 4 (FABP4, also known as aP2) in omental metastases as compared to primary ovarian tumors, and FABP4 expression was detected in ovarian cancer cells at the adipocyte-tumor cell interface. FABP4 deficiency substantially impaired metastatic tumor growth in mice, indicating that FABP4 has a key role in ovarian cancer metastasis. These data indicate adipocytes provide fatty acids for rapid tumor growth, identifying lipid metabolism and transport as new targets for the treatment of cancers where adipocytes are a major component of the microenvironment. PMID- 22037647 TI - Registered nurse retention strategies in nursing homes: a two-factor perspective. AB - BACKGROUND: As the American population ages and the proportion of individuals over the age of 65 expands, the demand for high-quality nursing home care will increase. However, nursing workforce instability threatens care quality and sustainability in this sector. Despite increasing attention to nursing home staff turnover, far less is known about registered nurse (RN) retention. PURPOSE: In this study, the relationships between retention strategies, employee benefits, features of the practice environment, and RN retention were explored. Further, the utility of Herzberg's two-factor theory of motivation as a framework for nursing home retention studies was evaluated. METHODOLOGY: This study was a secondary analysis of the nationally representative 2004 National Nursing Home Survey. The final sample of 1,174 participating nursing homes were either certified by Medicare or Medicaid or licensed by state agencies. We used a weighted multinomial logistic regression using an incremental approach to model the relationships. FINDINGS: Although most nursing homes offered some combination of retention programs, the majority of strategies did not have a significant association with the level of RN retention reported by facilities. Director of nursing tenure and other extrinsic factors had the strongest association with RN retention in adjusted analyses. PRACTICE IMPLICATIONS: To improve RN retention, organizations may benefit greatly from stabilizing nursing home leadership, especially the director of nursing position. Second, managers of facilities with poor retention may consider adding career ladders for advancement, awarding attendance, and improving employee benefits. As a behavioral outcome of motivation and satisfaction, retention was not explained as expected using Herzberg's two-factor theory. PMID- 22037648 TI - Investigating the impact of spatial priors on the performance of model-based IVUS elastography. AB - This paper describes methods that provide pre-requisite information for computing circumferential stress in modulus elastograms recovered from vascular tissue information that could help cardiologists detect life-threatening plaques and predict their propensity to rupture. The modulus recovery process is an ill-posed problem; therefore, additional information is needed to provide useful elastograms. In this work, prior geometrical information was used to impose hard or soft constraints on the reconstruction process. We conducted simulation and phantom studies to evaluate and compare modulus elastograms computed with soft and hard constraints versus those computed without any prior information. The results revealed that (1) the contrast-to-noise ratio of modulus elastograms achieved using the soft prior and hard prior reconstruction methods exceeded those computed without any prior information; (2) the soft prior and hard prior reconstruction methods could tolerate up to 8% measurement noise, and (3) the performance of soft and hard prior modulus elastograms degraded when incomplete spatial priors were employed. This work demonstrates that including spatial priors in the reconstruction process should improve the performance of model based elastography, and the soft prior approach should enhance the robustness of the reconstruction process to errors in the geometrical information. PMID- 22037649 TI - Radiochemotherapy with temozolomide for patients with glioblastoma. Prognostic factors and long-term outcome of unselected patients from a single institution. AB - BACKGROUND: The objective of this retrospective analysis was to assess long-term outcome and prognostic factors of unselected patients treated for glioblastoma (GB) at a single center with surgery, standard radiotherapy (RT), and concomitant temozolomide (TMZ). From 1999-2005, the institutional protocol included surgery and RT with TMZ. From 2005 on, adjuvant TMZ was routinely added. PATIENTS AND METHODS: Between April 1999 and September 2009, 181 patients with GB were treated with RT (60 Gy in 30 fractions) and concomitant TMZ (75 mg/m2/day throughout RT). Biopsy only had been performed in 53 patients (29.3%), 128 patients (70.7%) had undergone resection, which was complete based on postoperative MRI in 51 patients (28.2%). Adjuvant TMZ was applied in 67 of 181 patients (37%). RESULTS: Median overall survival (OS) and progression-free survival (PFS) were 15.0 (95% CI, 13.1 16.8) and 7.2 months (95% CI, 5.9-8.5), respectively. After complete resection, partial/subtotal resection and biopsy, median OS was 23.20, 14.75, and 7.89 months (p<0.001), respectively. In multivariate Cox proportional hazards regression models, extent of resection (p<0.0001), Karnofsky's performance score (p<0.0001) and adjuvant TMZ (p=0.001) were significant independent prognostic factors for OS. RT with concomitant TMZ was well tolerated in the majority of patients and could be completed as scheduled in 146 patients (80.7%), while 11 patients (6.1%) discontinued RT. Another 35 patients (19.3%) interrupted concomitant chemotherapy. CONCLUSION: RT with concomitant TMZ is a feasible regimen with acceptable toxicity in routine practice. Our data are compatible with a beneficial effect of adjuvant TMZ on OS and PFS. PMID- 22037650 TI - PET-guided dose escalation tomotherapy in malignant pleural mesothelioma. AB - PURPOSE: To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV). RESULTS: Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p=0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p=0.003). CONCLUSIONS: The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection. PMID- 22037651 TI - Curative treatment for central nervous system medulloepithelioma despite residual disease after resection. Report of two cases treated according to the GPHO Protocol HIT 2000 and review of the literature. AB - Medulloepithelioma of the central nervous system (CNS) is an uncommon primitive neuroectodermal tumor (PNET) usually occurring in early childhood. It is characterized by highly malignant behavior with a propensity for progression, recurrence, and dissemination despite intensive therapy. Due to its rarity, the optimal management is still unknown. However, gross total resection (GTR) has been considered crucial to achieve cure. In this article, the authors report on 2 cases of CNS medulloepithelioma in which long-term survival (more than 6 years) could be achieved despite evidence of, or suspected postoperative residual disease with an otherwise dismal prognosis.The patients were treated according to different strata of the protocol for primitive neuroectodermal tumors (PNET) of the German-Austrian multicenter trial of the German Society for Pediatric Oncology and Hematology (GPOH) for childhood brain tumors (HIT 2000). Treatment included postoperative hyperfractionated radiotherapy of the craniospinal axis followed by a boost to the tumor site in combination with chemotherapy. A review of the 2 reported and 37 previously published cases confirmed GTR and older age as positive prognostic factors. PMID- 22037652 TI - Comparison of different adjuvant radiotherapy approaches in childhood bladder/prostate rhabdomyosarcoma treated with conservative surgery. AB - BACKGROUND AND PURPOSE: Multimodality treatment approaches provide high local control and satisfying overall survival (OS) for children with localized bladder and/or prostate rhabdomyosarcoma (BP-RMS). However, current strategies including surgery and conventional radiotherapy are compromised by high rates of long-term genitourinary adverse effects. Therefore, a planning study combining organ preserving surgery with three different innovative adjuvant radiotherapy approaches was performed. PATIENTS AND METHODS: A case of a 21-month-old boy with BP-RMS treated with polychemotherapy according to the CWS 2002-P protocol, prostatectomy, partial cystectomy, and adjuvant high dose rate brachytherapy (HDR BT) was used to perform a planning study comparing HDR-BT with intensity modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) planning. RESULTS: All modalities provide good coverage of the target volume and spare critical normal tissues. Rectum doses could be reduced by 2/3 using IMPT and by 1/3 using BT compared to IMRT. In terms of sparing the pelvis growth plates, BT and IMPT are also superior to IMRT. CONCLUSION: All modalities provide good sparing of normal tissue. BT and IMPT are superior to IMRT with regard to doses on rectum and growth plates. BT is equivalent to IMPT in adequately selected tumors. PMID- 22037653 TI - [Survey of potential improvements during the course of the radiotherapy treatment -a patient questionnaire]. AB - INTRODUCTION AND BACKGROUND: In the context of quality assurance, increasing demands are placed on the whole radiotherapy treatment process. The patients directly concerned generally do not realize most aspects of the quality assurance program (e.g., additional safety checks) during their daily therapy. It was the aim of this study to systematically ask patients about potential improvements during the course of radiotherapy treatment from their own perspective. PATIENTS AND METHODS: In the defined time span (1 month), 624 radiotherapy patients (600 questionnaires were returned, 96.2%) were interviewed using a questionnaire newly developed to inquire about several aspects of their treatment. Furthermore, they were asked for their specific needs and suggestions for improvements that could be made during the course of radiotherapy treatment. RESULTS: Overall, the patients were satisfied with the course of their radiotherapy treatment and with patient care. As an example, about 90% agreed with the statement: "My first contact with the radiation oncology unit proceeded with kindness and competence so that I was given the impression that I will be well cared for in this clinic." Considering the organization of the course of radiotherapy, a large majority of patients attached great value to set appointments for the therapy fractions. A main point of criticism was waiting times or delays caused by servicing or machine failures. Small, low cost improvements as music in the therapy room were considered as important as expensive measures (e.g., daylight in the therapy room). The patients emphasized the importance of staff friendliness. CONCLUSION: The situation of radiotherapy patients was, in general, satisfactory. Future improvements can be mainly expected from smooth organisation of both planning and treatment which can be achieved by electronic scheduling systems. Many results of the survey could be easily implemented in daily practice. In matters of organization radiation oncology with its complex procedures can be used as a model for other clinical departments. PMID- 22037654 TI - Dose escalation of radiotherapy for metastatic spinal cord compression (MSCC) in patients with relatively favorable survival prognosis. AB - BACKGROUND AND PURPOSE: Local control of metastatic spinal cord compression (MSCC) is particularly important for long-term survivors. Radiotherapy alone is the most common treatment for MSCC. The most frequently used schedule world wide is 30 Gy/10 fractions. This study investigated whether patients with favorable survival prognoses benefit from a dose escalation beyond 30 Gy. PATIENTS AND METHODS: Data from 191 patients treated with 30 Gy/10 fractions were matched to 191 patients (1:1) receiving higher doses (37.5 Gy/15 fractions or 40 Gy/20 fractions). All patients had favorable survival prognoses based on a validated scoring system and were matched for age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, ambulatory status, and time developing motor deficits. Both groups were compared for local control, progression-free survival, overall survival, and functional outcome. RESULTS: Local control rates at 2 years were 71% after 30 Gy and 92% after higher doses (p=0.012). Two-year progression free survival rates were 68% and 90%, respectively (p=0.013). Two-year overall survival rates were 53% and 68%, respectively (p=0.032). Results maintained significance in the multivariate analyses (Cox proportional hazards model; stratified model) with respect to local control (p=0.011; p=0.012), progression free survival (p=0.010; p=0.018), and overall survival (p=0.014; p=0.015). Functional outcome was similar in both groups. Motor function improved in 40% of patients after 30 Gy and 41% after higher doses (p=0.98). CONCLUSION: Escalation of the radiation dose beyond 30 Gy resulted in significantly better local control, progression-free survival, and overall survival in patients with favorable survival prognoses. PMID- 22037655 TI - Dysphagia. Impact on quality of life after radio(chemo)therapy of head and neck cancer. AB - BACKGROUND: In the past, xerostomia was considered one of the most important determining factors of quality of life (QoL) after radiotherapy (RT) of the head and neck region. In addition, more recent studies have shown that RT-induced dysphagia has an essential influence on the QoL. PATIENTS AND METHODS: Between September 2005 and August 2007, 35 patients with locally advanced squamous cell carcinoma of the head and neck region were included in the prospective study. Patients were treated by IMAT (intensity-modulated arc therapy) or IMRT (intensity-modulated radiotherapy) planned on 3D imaging. A total of 28 patients (80%) received concomitant chemotherapy. The evaluation of QoL (EORTC QLQ-C30, H&N C-35) and toxicities (CTC 2.0) were assessed at the beginning of, during, and after RT as well as up to 12 months after the end of therapy. RESULTS: At the end of therapy, 86% of the patients experienced difficulties in swallowing (62% CTC II-III degrees ). Twelve months after the end of treatment, 15% still suffered from dysphagia CTC II-III degrees . Concomitant chemotherapy exacerbated the incidence and gravity of dysphagia, resulting in increasing dietary problems. QoL (EORTC) was significantly affected by dysphagia. In particular, the global state of health and QoL were influenced at the end of treatment (p=0.033) and at a later stage (p=0.050). CONCLUSION: The findings of this study suggest that more emphasis should be placed on structured clinical diagnostics, therapy, and rehabilitation of deglutition problems. This means in particular to not only spare the parotids while planning the irradiation, but also to take into consideration the important structures for deglutition, like the retropharyngeal muscles. PMID- 22037656 TI - Imaging of female pelvic malignancies regarding MRI, CT, and PET/CT: Part 2. AB - PURPOSE: To compose diagnostic standard operating procedures for both clinical and imaging assessment for vulvar and vaginal cancer, for vaginal sarcoma, and for ovarian cancer. METHODS: The literature was reviewed for diagnosing the above mentioned malignancies in the female pelvis. Special focus herein lies in tumor representation in MRI, followed by the evaluation of CT and PET/CT for this topic. CONCLUSION: MRI is a useful additional diagnostic complement but by no means replaces established methods of gynecologic diagnostics and ultrasound. In fact, MRI is only implemented in the guidelines for vulvar cancer. According to the current literature, CT is still the cross-sectional imaging modality of choice for evaluating ovarian cancer. PET/CT appears to have advantages for staging and follow-up in sarcomas and cancers of the ovaries. PMID- 22037657 TI - Letter to the Editor on: A. Siegmann et al. Dose escalation for patients with decreasing PSA during radiotherapy for elevated PSA after radical prostatectomy improves biochemical progression-free survival. Results of a retrospective study. In: Strahlenther Onkol 2011;187:467-72 (No. 8) (DOI 10.1007/s00066-011-2229-3). P. Ghadjar, D. Zwahlen, D.M. Aebersold: Selection bias is not a good reason for dose intensification in patients with PSA recurrence after radical prostatectomy. PMID- 22037658 TI - Pancreatic adenocarcinoma with multiple eosinophilic extracellular deposits consistent with noncalcified psammoma bodies. PMID- 22037659 TI - In situ high pressure study of ZIF-8 by FTIR spectroscopy. AB - ZIF-8 as a promising storage material was investigated at high pressures up to ~39 GPa by in situ FTIR spectroscopy for the first time. Structural modifications are found to be reversible in a low-pressure region but irreversible in a high pressure region. Overall, the ZIF-8 framework exhibits an unusual chemical stability even under extreme compression. PMID- 22037660 TI - Characterization of chromophoric dissolved organic matter (CDOM) in rainwater using fluorescence spectrophotometry. AB - The fluorescence excitation-emission matrix of Chromophoric dissolved organic matter (CDOM) samples from rainwater collected at Rameswaram, Tamilnadu, India are analysed. Total five peaks were observed for humic/marine and protein likes substances respectively. The peak A and C intensities varies form 1.98 +/- 0.28 and 0.97 +/- 0.11 QSU respectively represents humic like substances. The peak B and T intensities varies from 3.94 +/- 0.75 and 7.42 +/- 1.43 QSU showed association of protein like substances whereas peak M intensities varies from 1.92 +/- 0.37 QSU indicates marine contribution. Among the fluorophores, the following sequence were observed as T > B > A > M > C which indicates dominance of Tryptophan like substances in rainwater. The average peak T/C ratios was observed as 7.88 +/- 2.2 indicates microbial contamination by Tryptophan-like substances with the high biological activity and low volatility. PMID- 22037661 TI - Trace elements in tissues of wild carnivores and omnivores in Croatia. AB - The differences in metal exposure (As, Cd, Cu, Pb and Hg) in the muscle, liver and kidney tissues of brown bears (Ursus arctos), grey wolfs (Canis lupus), Eurasian lynxs (Lynx lynx), Eurasian badgers (Meles meles) and pine martens (Martes martes) from Croatia were observed. The highest mean Cd levels were found in kidney and liver of Eurasian badger (3.05 and 0.537 mg/kg). The highest Cu concentrations (mg/kg) measured in liver tissue were obtained in order: Eurasian badger (15.2) > brown bear (12.1) > pine marten (10.3) > Eurasian lynx (8.43) > grey wolf (6.44). Result presented that Eurasian badger accumulated the highest levels of elements: As, Cu and Pb in muscle; As, Cd, Cu and Pb in liver; Cd and Pb in kidney. Kidney of pine marten accumulated the highest concentrations of As, Cu and Hg. Omnivorous species observed present an important bioindicator for the accumulation of toxic elements indicating an enhanced vulnerability for response to ecological changes in forested terrain. Generally, element concentrations found in five species observed were lower in comparison to levels reported in previous studies and below levels related to toxicosis in mammals. PMID- 22037662 TI - Selective and non-selective intrauterine growth restriction in twin pregnancies: high-risk factors and perinatal outcome. AB - PURPOSE: To evaluate the high-risk factors and perinatal outcome in selective intrauterine growth restriction (sIUGR) and non-selective IUGR (non-sIUGR) in twins. METHODS: In total, 336 pairs of twins were enrolled from December 2003 to 2009. According to the birth weight, 295 pairs of twins were divided into sIUGR, non-sIUGR and normal growth groups. Maternal characteristics, complications, chorionicity, zygosity and perinatal outcomes were analyzed among the three groups. RESULTS: The overall IUGR incidence (including sIUGR and non-sIUGR) in twin pregnancies was 23.2%. The sIUGR incidence was ten times greater than that of non-sIUGR. Monochorionicity and monozygosity were risk factors for overall IUGR, especially for the sIUGR (P < 0.01). Pre-eclampsia was more common in sIUGR than in the normal growth group (P < 0.05). Both the sIUGR and non-sIUGR groups had more intrauterine fetal death and neonatal death than the normal growth group (P < 0.01). The sIUGR group had more brain injury than the normal growth group (P < 0.01). CONCLUSION: Monochorionicity, monozygosity, pre-eclampsia were high-risk factors for IUGR in twins. Perinatal death was more prevalent in the non-sIUGR group, and neonatal brain damage was more prevalent in the sIUGR group. PMID- 22037663 TI - DNA in a modern world. PMID- 22037664 TI - Virtual intergovernmental linkage through the Environmental Information Exchange Network. AB - Over the past decade the U.S. Environmental Protection Agency (EPA) and the states have partnered in developing a web-based information sharing initiative that provides state environmental agencies easy access to federal environmental monitoring data and to the environmental data of other states, and gives the EPA access to data from state sources. The Environmental Information Exchange Network (EIEN) has established basic data exchange nodes in each of the states. Using multiple regression analysis we investigate the factors that account for the number and development stage of the data exchanges in which the states participate as of 2009. Overall, we find that administrative factors, especially the EPA's grant program, are more important than political or environmental conditions. Participation in the exchanges is important not only as a way to reduce costs for data reporting and communication, but also as a precursor to greater eventual interstate environmental collaboration. Though clear evidence of a transition to collaboration is not yet seen here, there are some indications it may emerge in time. PMID- 22037665 TI - Effects of intravenous iron saccharate on improving severe anemia in rheumatoid arthritis patients. AB - Anemia in rheumatoid arthritis (RA) is multifactorial. Iron deficiency, either definite or relative (defect in iron utilization), exists in RA patients with anemia. Intravenous iron therapy is indicated in severe and symptomatic cases or those with conditions precluding use of oral iron, but its safety and long-term efficacy have not been well-established. Forty severe anemic (hemoglobin < 9 g/dL) RA patients with or without demonstrable bone marrow iron stain were enrolled in this study. Fractionated administration of intravenous iron saccharate was undertaken and the median follow-up time was 1 year. All patients exhibited significant elevations of hemoglobin 3 months after treatment, which were more pronounced in the nonstainable iron marrow subjects {median (interquartile range): 3.8 (2.9-4.8) g/dL versus 2.9 (2.0-3.0) g/dL, p < 0.01}. Thereafter, hemoglobin remained at a plateau level that lasted during the observation period. Throughout the whole course, none of the cases exhibited side effects or flare up of disease activities. The use of intravenous iron saccharate, preferably administrated in a fractionated way, is effective in the correction of severe anemia in RA patients, especially those with nonstainable iron marrow. PMID- 22037666 TI - Molecular characterization and tandem mass spectrometry of the lectin extracted from the seeds of Dioclea sclerocarpa Ducke. AB - Lectin from the seeds of Dioclea sclerocarpa (DSL) was purified in a single step by affinity chromatography on a Sephadex G-50 column. The primary sequence, as determined by tandem mass spectrometry, revealed a protein with 237 amino acids and 81% of identity with ConA. DSL has a molecular mass of 25,606 Da. The beta and gamma chains weigh 12,873 Da and 12,752 Da, respectively. DSL hemagglutinated rabbit erythrocytes (both native and treated with proteolytic enzymes), showing stability even after one hour of exposure to a specific pH range. The hemagglutinating activity of DSL was optimal between pH 6.0 and 8.0, but was inhibited after incubation with D-galactose and D-glucose. The pure protein possesses a molecular mass of 25 kDa by SDS-PAGE and 25,606 Da by mass spectrometry. The secondary structure content was estimated using the software SELCON3. The results indicate that b-sheet secondary structures are predominant in DSL (approximately 42.3% antiparallel b-sheet and 6.7% parallel b-sheet). In addition to the b-sheet, the predicted secondary structure of DSL features 4.1% a helices, 15.8% turns and 31.3% other contributions. Upon thermal denaturation, evaluated by measuring changes in ellipticity at 218 nm induced by a temperature increase from 20 degrees C to 98 degrees C, DSL displayed cooperative sigmoidal behavior with transition midpoint at 84 degrees C and permitted the observation of two-state model (native and denatured). PMID- 22037667 TI - Phytoceramide shows neuroprotection and ameliorates scopolamine-induced memory impairment. AB - The function and the role phytoceramide (PCER) and phytosphingosine (PSO) in the central nervous system has not been well studied. This study was aimed at investigating the possible roles of PCER and PSO in glutamate-induced neurotoxicity in cultured neuronal cells and memory function in mice. Phytoceramide showed neuro-protective activity in the glutamate-induced toxicity in cultured cortical neuronal cells. Neither phytosphingosine nor tetraacetylphytosphingosine (TAPS) showed neuroproective effects in neuronal cells. PCER (50 mg/kg, p.o.) recovered the scopolamine-induced reduction in step through latency in the passive avoidance test; however, PSO did not modulate memory function on this task. The ameliorating effects of PCER on spatial memory were confirmed by the Morris water maze test. In conclusion, through behavioral and neurochemical experimental results, it was demonstrated that central administration of PCER produces amelioration of memory impairment. These results suggest that PCER plays an important role in neuroprotection and memory enhancement and PCER could be a potential new therapeutic agent for the treatment of neurodegenerative diseases such as Alzheimer's disease. PMID- 22037668 TI - Retrieving microcatheters from Onyx casts in a series of brain arteriovenous malformations: a technical report. AB - INTRODUCTION: To date, the "monorail snare technique" for the retrieval of entombed microcatheter tips during Onyx(TM) (ev3, Irvine, CA) embolisation of brain arteriovenous malformations (BAVM) has not been described. We report our experiences and some technical aspects in using this technique for the retrieval of entombed Marathon(TM) microcatheter (ev3, Plymouth, MN) tips during Onyx embolisation of BAVM treatment. METHODS: Onyx was used in the embolisation of 11 patients using 25 feeders over 14 sessions. The 'monorail snare technique' was employed for 14 feeders. Each time, an Amplatz 4 mm Gooseneck Microsnare(TM) (ev3, Plymouth, MN) was loaded into an Excelsior 1018(TM) microcatheter (Boston Scientific, Natick, MA). The Marathon microcatheter was cut just distal to the hub, and the Amplatz/Excelsior combination was introduced along the length of the Marathon microcatheter towards its distal end, as far as possible. The embedded catheter was ensnared and both catheters were pulled free. RESULTS: Microcatheter tip removal was successful in all cases, except for one microcatheter tip becoming detached and needing no further intervention. There were no complications as a direct result of the snare technique. CONCLUSIONS: The monorail snare technique is a safe and easy technique for retrieving Onyx-encased microcatheter tips in the treatment of BAVM. PMID- 22037669 TI - Stone handling behavior in rhesus macaques (Macaca mulatta), a behavioral propensity for solitary object play shared with Japanese macaques. AB - Stone handling (SH) behavior was systematically studied in a captive troop of rhesus macaques housed at the Primate Research Institute of Kyoto University, and compared with the results of long-term studies of this behavior in Japanese macaques, to evaluate the similarities of SH behavior in these two closely related species. Similar to Japanese macaques, rhesus macaques showed age-related differences in SH. Young animals were more active and displayed more SH patterns and bouts than did adults. Furthermore, the young displayed SH at a higher frequency and their bouts were of a shorter duration, compared to adults. Young adults were more active and displayed more patterns than did older adults. On the other hand, older adults were more conservative and displayed fewer patterns, and engaged in them for longer durations. All individuals displayed SH more frequently in relaxed environmental and social conditions. While lacking an apparent immediate adaptive value, practice of the behavior has been proposed to have long-term functional value for neural and cognitive development in the young and for the maintenance or repair of neuro-pathways in aging macaques that habitually perform the behavior. The results presented here are consistent with what we know about Japanese macaque SH. Given the uniformity of SH behavioral parameters and these two macaque species' close phylogenetic relatedness, we propose that a similar functional and adaptive value for SH can be inferred for rhesus macaques. PMID- 22037670 TI - Fate of the teratogenic and carcinogenic ochratoxin A in human perfused placenta. AB - Ochratoxin A (OTA) is one of the most frequent mycotoxins detected in human blood worldwide. Apart from its well known nephrotoxicity, OTA-induced teratogenicity and carcinogenicity proven in animals are potential effects also in humans. Pregnant women have been exposed to this food contaminant via dietary exposure in a continuous and widespread manner. Although the transplacental transfer of OTA has been demonstrated in laboratory animals and the presence of OTA in human fetal samples has been reported, little is known about the role of human placenta in OTA toxicokinetics. In this study, human perfused placenta was used to reveal the actual placental toxicokinetics of OTA using concentrations found in serum of pregnant women. Moreover, the effect of protein concentration and biological significance of placental transporters on the OTA transfer in human placenta were also determined. Our study is the first to pursue the transfer of OTA through perfused human placenta. The transfer of OTA through term human placenta was barely detectable in all perfusions. Inhibitors of neither ABCG2 nor ABCC2 increased the transport of OTA to fetal circulation in placental perfusion, and thus these transporters apparently do not have biological significance in inhibiting transplacental transfer of OTA. Human albumin has inhibited OTA transfer through a tight monolayer of BeWo b30 cells. Finding from this study clearly contradict the existing epidemiological studies reporting higher OTA levels in fetal than in maternal circulation in vivo. PMID- 22037671 TI - Optical negative refraction by four-wave mixing in thin metallic nanostructures. AB - The law of refraction first derived by Snellius and later introduced as the Huygens-Fermat principle, states that the incidence and refracted angles of a light wave at the interface of two different materials are related to the ratio of the refractive indices in each medium. Whereas all natural materials have a positive refractive index and therefore exhibit refraction in the positive direction, artificially engineered negative index metamaterials have been shown capable of bending light waves negatively. Such a negative refractive index is the key to achieving a perfect lens that is capable of imaging well below the diffraction limit. However, negative index metamaterials are typically lossy, narrow band, and require complicated fabrication processes. Recently, an alternative approach to obtain negative refraction from a very thin nonlinear film has been proposed and experimentally demonstrated in the microwave region. However, such approaches use phase conjugation, which makes optical implementations difficult. Here, we report a simple but different scheme to demonstrate experimentally nonlinear negative refraction at optical frequencies using four-wave mixing in nanostructured metal films. The refractive index can be designed at will by simply tuning the wavelengths of the interacting waves, which could have potential impact on many important applications, such as superlens imaging. PMID- 22037672 TI - Treatment of pediatric urolithiasis: how small is "small enough"? PMID- 22037673 TI - MRI driven magnetic microswimmers. AB - Capsule endoscopy is a promising technique for diagnosing diseases in the digestive system. Here we design and characterize a miniature swimming mechanism that uses the magnetic fields of the MRI for both propulsion and wireless powering of the capsule. Our method uses both the static and the radio frequency (RF) magnetic fields inherently available in MRI to generate a propulsive force. Our study focuses on the evaluation of the propulsive force for different swimming tails and experimental estimation of the parameters that influence its magnitude. We have found that an approximately 20 mm long, 5 mm wide swimming tail is capable of producing 0.21 mN propulsive force in water when driven by a 20 Hz signal providing 0.85 mW power and the tail located within the homogeneous field of a 3 T MRI scanner. We also analyze the parallel operation of the swimming mechanism and the scanner imaging. We characterize the size of artifacts caused by the propulsion system. We show that while the magnetic micro swimmer is propelling the capsule endoscope, the operator can locate the capsule on the image of an interventional scene without being obscured by significant artifacts. Although this swimming method does not scale down favorably, the high magnetic field of the MRI allows self propulsion speed on the order of several millimeter per second and can propel an endoscopic capsule in the stomach. PMID- 22037674 TI - Hydrophilic interaction and reversed-phase ultraperformance liquid chromatography TOF-MS for serum metabonomic analysis of myocardial infarction in rats and its applications. AB - An ultra performance liquid chromatography coupled to mass spectrometry-based metabonomic approach, which utilizes both reversed-performance (RP) chromatography and hydrophilic interaction chromatography (HILIC) separations, has been developed to characterize the global serum metabolic profile associated with myocardial infarction (MI). The HILIC was found necessary for a comprehensive serum metabonomic profiling, providing complementary information to RP chromatography. By combining with partial least squares discriminant analysis, 21 potential biomarkers in rat serum were identified. To further elucidate the pathophysiology of MI, related metabolic pathways have been studied. It was found that MI was closely related to disturbed sphingolipid metabolism, phospholipid catabolism, fatty acid transportation and metabolism, tryptophan metabolism, branched-chain amino acids metabolism, phenylalanine metabolism, and arginine and proline metabolism. With the presented metabonomic method, we systematically analyzed the therapeutic effects of Traditional Chinese Medicine Sini decoction (SND). The results demonstrated that SND administration could provide satisfactory effects on MI through partially regulating the perturbed metabolic pathways. PMID- 22037675 TI - The functional relationship between ectodermal and mesodermal segmentation in the crustacean, Parhyale hawaiensis. AB - In arthropods, annelids and chordates, segmentation of the body axis encompasses both ectodermal and mesodermal derivatives. In vertebrates, trunk mesoderm segments autonomously and induces segmental arrangement of the ectoderm-derived nervous system. In contrast, in the arthropod Drosophila melanogaster, the ectoderm segments autonomously and mesoderm segmentation is at least partially dependent on the ectoderm. While segmentation has been proposed to be a feature of the common ancestor of vertebrates and arthropods, considering vertebrates and Drosophila alone, it is impossible to conclude whether the ancestral primary segmented tissue was the ectoderm or the mesoderm. Furthermore, much of Drosophila segmentation occurs before gastrulation and thus may not accurately represent the mechanisms of segmentation in all arthropods. To better understand the relationship between segmented germ layers in arthropods, we asked whether segmentation is an intrinsic property of the ectoderm and/or the mesoderm in the crustacean Parhyale hawaiensis by ablating either the ectoderm or the mesoderm and then assaying for segmentation in the remaining tissue layer. We found that the ectoderm segments autonomously. However, mesoderm segmentation requires at least a permissive signal from the ectoderm. Although mesodermal stem cells undergo normal rounds of division in the absence of ectoderm, they do not migrate properly in respect to migration direction and distance. In addition, their progeny neither divide nor express the mesoderm segmentation markers Ph-twist and Ph-Even-skipped. As segmentation is ectoderm-dependent in both Parhyale and holometabola insects, we hypothesize that segmentation is primarily a property of the ectoderm in pancrustacea. PMID- 22037677 TI - Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery. AB - Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R2 = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with alpha/beta values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases. PMID- 22037676 TI - Intramuscular adipose is derived from a non-Pax3 lineage and required for efficient regeneration of skeletal muscles. AB - Ectopic accumulation of adipose in the skeletal muscle is associated with muscle wasting, insulin resistance and diabetes. However, the developmental origin of postnatal intramuscular adipose and its interaction with muscle tissue are unclear. We report here that compared to the fast EDL muscles, slow SOL muscles are more enriched with adipogenic progenitors and have higher propensity to form adipose. Using Cre/LoxP mediated lineage tracing in mice, we show that intramuscular adipose in both EDL and SOL muscles is exclusively derived from a Pax3(-) non-myogenic lineage. In contrast, inter-scapular brown adipose is derived from the Pax3(+) lineage. To dissect the interaction between adipose and skeletal muscle tissues, we used Myf5-Cre and aP2-Cre mice in combination with ROSA26-iDTR mice to genetically ablate myogenic and adipogenic cell lineages, respectively. Whereas ablation of the myogenic cell lineage facilitated adipogenic differentiation, ablation of the adipogenic cell lineage surprisingly impaired the regeneration of acutely injured skeletal muscles. These results reveal striking heterogeneity of tissue-specific adipose and a previously unappreciated role of intramuscular adipose in skeletal muscle regeneration. PMID- 22037678 TI - Accumulation of chromium and lead in bryophytes and pteridophytes in a stream affected by tannery wastewater. AB - The concentrations of Cr and Pb were determined in bryophytes and pteridophytes sampled in a stream near a tannery in Guarapuava, southern Brazil. The concentrations of Cr and Pb were measured by cathodic and anodic voltammetry, respectively. These plants were used to evaluate the spatial distribution of elements in the examined stream, and contained elevated levels of Cr (0.71-24.07 MUg/g) and Pb (4.33-24.20 MUg/g). Chromium levels in plants near the tannery greatly exceeded background levels, indicating a severe to extreme degree of contamination with this metal. Lead levels were elevated to a lesser degree, indicating slight to moderate contamination for most plants collected near the tannery. PMID- 22037679 TI - Isomeric Fe(II) MOFs: from a diamond-framework spin-crossover material to a 2D hard magnet. AB - Two Fe(II) coordination polymers formed from isomeric ligands give a diamond-like 3D network exhibiting a gradual SCO and a 2D hard magnet with a large coercive field. PMID- 22037680 TI - Local and remote cellular responses following a surgical lesion in the Cebus apella cerebral cortex. AB - Distribution of bromodeoxyuridine immunoreactive (BrdU-IR) cell nuclei was analyzed at proximal and remote cortical sites in adult Cebus apella monkeys after a programmed surgical lesion placed either in the prefrontal or in the striate cerebral cortex. Increased GFAP-IR and vimentin-IR astrocytes, as well as IsolectinB4 labeled microglial cells, were observed both at lesional and perilesional areas. After injury at either location, the BrdU nuclear incorporation spread to supragranular layers in remote cortical areas functionally related to the injured cortex, probably due to involvement of degenerated cortico-cortical association fibers. Double labeling with Ki-67 suggested that remote BrdU-IR nuclei belong to proliferating cells, but the cell type remains to be determined, since these nuclei did not correspond to NeuN, MAP2, GFAP, Vimentin and isolectinB4 labeled cells. This remote effect should be incorporated to current clinical and experimental appraisal of cortical lesions. PMID- 22037681 TI - An integrated air quality forecast system for a metropolitan area. AB - Air quality forecasting is an important issue in environmental research, due to the effects that air pollutants have on population health. To deal with this topic, in this work an integrated modelling system has been developed to forecast daily maximum eight hours ozone concentrations and daily mean PM10 concentrations, up to two days in advance, over an urban area. The presented approach involves two steps. In the first step, artificial neural networks are identified and applied to get point-wise forecasting. In the second step, the forecasts obtained at the monitoring station locations are spatially interpolated all over the domain using the cokriging technique, which allows to improve the spatial interpolation in the absence of densely sampled data. The integrated modelling system has been then applied to a case study over Northern Italy, performing a validation over space and time for the year 2004 and analyzing if the limit values for the protection of human health set by the European Commission are respected. The presented approach represents a fast and reliable way to provide decision makers and the general public with air quality forecasting, and to support prevention and precautionary measures. PMID- 22037682 TI - A review of the problematic adhesion prophylaxis in gynaecological surgery. AB - BACKGROUND: Adhesions lead to considerable patient morbidity and are a mounting burden on surgeons and the health care system alike. Although adhesion formation is the most frequent complication in abdominal and pelvic surgery, many surgeons are still not aware of the extent of the problem. To provide the best care for their patients, surgeons should consistently inform themselves of anti-adhesion strategies and include these methods in their daily routine. METHODS: Searches were conducted in PubMed and The Cochrane Library to identify relevant literature. FINDINGS: Various complications are associated with adhesion formation, including small bowel obstruction, infertility and chronic pelvic pain. Increasingly, an understanding of adhesion formation as a complex process influenced by many different factors has led to various conceivable anti-adhesion strategies. At present, a number of different anti-adhesion agents are available. Although some agents have proved effective in reducing adhesion formation in randomised controlled trials, none of them can completely prevent adhesion formation. CONCLUSION: To fulfil our duty to provide best possible care for our patients, it is now time to regard adhesions as the most common complication in surgery. Further research is needed to fully understand adhesion formation and to develop new strategies for adhesion prevention. Large clinical efficacy trials of anti-adhesion agents will make it easier for surgeons to decide which agent to use in daily routine. PMID- 22037683 TI - Placental alpha microglobulin-1 (AmniSure((r)) test) for detection of premature rupture of fetal membranes. AB - OBJECTIVES: This study was designed to detect the accuracy of the placental alpha microglobulin-1 (PAMG-1) (AmniSure((r)) test) to diagnose premature rupture of the fetal membranes (PROM). STUDY DESIGN: This comparative prospective study was carried out over 2 years in Al-Rashid Maternity Hospital, Kuwait from January 2006 till January 2008. PATIENTS AND METHODS: One hundred and fifty (150) pregnant women after 37 weeks gestation were included in this study for induction of labor and divided into two groups according to the presence or absence of PROM; 75 patients with PROM were included in group I and 75 patients without PROM were included in group II as controls. Patients with multiple pregnancies or fetal distress or vaginal bleeding or preterm labor or chorioamnionitis were excluded from this study. Trans-abdominal ultrasound was done to detect the gestational age and the amniotic fluid index (AFI <=5 cm in PROM) followed by sterile speculum examination to detect amniotic fluid pooling from the cervical canal and for the collection of samples. RESULTS: In this study, the sensitivity and the specificity of PAMG-1 to diagnose PROM were 97.33 and 98.67%, respectively, compared with 84% sensitivity and 78.67% specificity for Ferning test and 86.67% sensitivity and 81.33% specificity for Nitrazine test. The positive predictive value (PPV) and negative predictive value (NPV) of PAMG-1 were 98.64 and 97.37%, respectively, compared with 79.74% PPV and 83.1% NPV for Ferning test and 82.28% PPV and 85.91% NPV for Nitrazine test. PAMG-1 was accurate (98%) for detection of PROM than Ferning (81.33%) or Nitrazine (84.0%) tests. CONCLUSION: Detection of the PAMG-1 in the vaginal fluid using AmniSure((r)) test is an accurate method to diagnose rupture of the fetal membranes, with high sensitivity, specificity, negative and positive predictive values. PMID- 22037684 TI - First report of reproductive assistance in a woman affected by May-Hegglin anomaly. AB - PURPOSE: To report the first case of fertility treatment in a patient with May Hegglin anomaly, a rare hematological disorder inherited as an autosomal dominant trait. METHOD: We present a case report of a 40-year-old nulliparous patient with May-Hegglin anomaly who underwent her first ICSI cycle with transfer of three fresh embryos. RESULTS: Prophylactic platelet transfusion obtained by single donor apheresis was performed 1 h before the oocyte pick up. No complications were reported. No pregnancy was obtained. CONCLUSIONS: We report about the possibility to assist women affected by May-Hegglin anomaly requiring reproductive assistance. However, a multidisciplinary team composed of gynecologists and hematologists should follow such patients carefully, in order to carry out a complete clinical evaluation and to prevent the potential risks of bleeding. Clinicians must be vigilant in their presentation of risks, benefits, and alternatives. PMID- 22037685 TI - Antiproliferative activity of lignans against the breast carcinoma cell lines MCF 7 and BT 20. AB - PURPOSE: Phytoestrogens are plant-derived, non-steroidal phytochemicals with anticarcinogenic potential. The major structural classes are the isoflavones and lignans. The aim of this study was to compare the effect of the plant-derived lignans secoisolariciresinol and matairesinol with the human lignans enterodiol and enterolactone as well as with 17beta estradiol and tamoxifen on cell proliferation of breast carcinoma cell lines. METHODS: The influence of the lignans, 17beta estradiol and tamoxifen on cell proliferation was determined using the BrdU test in MCF 7 and BT 20 cell lines. RESULTS: Enterodiol and enterolactone induced a stronger inhibition of cell growth in MCF 7 and BT 20 cells than secoisolariciresinol and matairesinol. The inhibition effects were less expressed in the BT 20 than in the MCF 7 cells. CONCLUSIONS: The human lignans enterodiol and enterolactone are more biologically active than their precursors secoisolariciresinol and matairesinol, and may be defined as the real drugs in cancer prevention. PMID- 22037686 TI - Skin closure with subcuticular absorbable staples after cesarean section is associated with decreased analgesic use. AB - PURPOSE: To determine if skin closure with subcuticular absorbable staples at the time of cesarean section is associated with decreased in-hospital analgesic use compared to skin closure with surgical steel staples. METHODS: A retrospective cohort study was performed between 1 January 2005 and 31 December 2008 comparing in-hospital analgesic use after cesarean section between patients ,who underwent skin closure with surgical steel staples and subcuticular absorbable polyglycolic acid staples. RESULTS: Eighty-nine subjects were included in the absorbable staple cohort and 95 were included in the steel staple group. There was a 1.5 fold decrease in ketorolac use (p < 0.0001) and a trend toward decreased ibuprofen use in the absorbable staple cohort (p = 0.06). There was no difference in hydrocodone/acetaminophen use between groups (p = 0.89). CONCLUSIONS: Our results suggest that the use of subcuticular absorbable staples for skin closure at the time of cesarean section may lead to less in-hospital analgesic use, and thereby positively impact a patient's post-operative course. In addition, while reduced analgesic use may represent a small cost savings for each individual patient, there is the potential for significant savings when one considers the large number of cesarean sections performed in the US annually. Prospective studies will be required to assess the full impact of the use of this new skin closure technology. PMID- 22037687 TI - Distinct but overlapping neural networks subserve depression and insecure attachment. AB - Insecure attachment has been linked to depression and to outcome in psychotherapy. The neural mechanisms subserving the relationship between attachment security and depression are not well understood. We have developed a method to examine attachment-related brain activity in depression. Twenty-eight women, half depressed, viewed images of their mother, a female friend, and female strangers during fMRI scanning. The effects of depression and insecure attachment were determined with whole-brain multiple linear regression of blood-oxygen-level dependent response against subjects' Beck Depression Inventory and Adult Attachment Interview (AAI) coherence of mind scores. Interaction effects were analyzed with ANOVA. Activity associated with depression and with insecure attachment was found in the cortico-striato-thalamic circuits of affect regulation. For early attachment (mother-friend contrast), depression scores correlated with activation of cortical and sub-cortical components of these circuits, while attachment insecurity correlated with sub-cortical activity in the same circuitry. Depression and attachment insecurity correlated with both cortical and sub-cortical activities for mother-stranger, and areas of overlap and of enhancing interactions between depression and insecure attachment were found. For late attachment (friend-stranger contrast), only cortical effects were found. Depression and attachment insecurity may be subserved by similar but distinct components of affect regulating circuits. Their interactions may explain the greater difficulty of treating depression in insecurely attached patients and suggest a contributing role for insecure attachment in depression. Further, differential sub-cortical vs cortical encoding of early vs late attachment suggests a top-down model of late attachment, potentially relevant to psychotherapeutic outcome. PMID- 22037688 TI - Breakdown in the brain network subserving moral judgment in criminal psychopathy. AB - Neuroimaging research has demonstrated the involvement of a well-defined brain network in the mediation of moral judgment in normal population, and has suggested the inappropriate network use in criminal psychopathy. We used functional magnetic resonance imaging (fMRI) to prove that alterations in the brain network subserving moral judgment in criminal psychopaths are not limited to the inadequate network use during moral judgment, but that a primary network breakdown would exist with dysfunctional alterations outside moral dilemma situations. A total of 22 criminal psychopathic men and 22 control subjects were assessed and fMRI maps were generated to identify (i) brain response to moral dilemmas, (ii) task-induced deactivation of the network during a conventional cognitive task and (iii) the strength of functional connectivity within the network during resting-state. The obtained functional brain maps indeed confirmed that the network subserving moral judgment is underactive in psychopathic individuals during moral dilemma situations, but the data also provided evidence of a baseline network alteration outside moral contexts with a functional disconnection between emotional and cognitive elements that jointly construct moral judgment. The finding may have significant social implications if considering psychopathic behavior to be a result of a primary breakdown in basic brain systems. PMID- 22037689 TI - Oxytocin decreases handgrip force in reaction to infant crying in females without harsh parenting experiences. AB - Infant crying can elicit sensitive caregiving as well as hostility and harsh parenting responses. In the current study (N = 42 females) with a double-blind experimental design, we tested the effect of intranasal oxytocin administration on the use of excessive force using a hand-grip dynamometer during listening to infant cry sounds. Participants' experiences with harsh parental discipline during childhood were found to moderate the effect of oxytocin administration on the use of excessive force. Participants' whose parents did not discipline them harshly used less excessive force in the oxytocin condition, but for participants who were disciplined harshly there was no difference between the oxytocin and placebo condition. Such effects were not found during listening to infant laughter. We conclude that early caregiving experiences constitute an important moderator of the prosocial and/or stress-reducing effects of oxytocin. Oxytocin administration may increase trust and cooperation in individuals with supportive backgrounds, but not generate this effect in individuals who as a consequence of unfavorable early caregiving experiences may have a bias toward negative interpretation of social cues. PMID- 22037690 TI - Duct-to-duct biliary reconstruction during complex hepatectomy: a useful technique in selected cases. AB - BACKGROUND: Roux-en-Y anastomosis is the standard of care for biliary reconstruction. Yet, a direct bilio-biliary anastomosis preserves the normal sphincter mechanism and endoscopic access to the biliary tree for diagnostic and therapeutic purposes. Duct-to-duct biliary reconstruction is widely used in liver transplantation. The objective of this study was to analyze the feasibility and results of duct-to-duct biliary reconstruction in the setting of complex hepatic resection with limited biliary confluence involvement. METHODS: We identified patients from our prospectively maintained database that underwent major hepatic resection and bile duct resection with a concomitant direct duct-to-duct biliary anastomosis. Postoperative oncological and functional biliary outcomes were analyzed. RESULTS: Ten patients were studied. In 9 cases, a biliary stent was left in place to decompress the anastomosis. Two patients developed a biliary fistula: one resolved spontaneously and the other required percutaneous drainage and an endoscopic biliary stent. This latter patient (the only nonstented patient) also developed a biliary stricture that was treated endoscopically. With a mean follow-up of 22 months, no other biliary-related complications were recorded. No patients had a recurrence at the biliary reconstruction site only. In the setting of multifocal hepatic recurrence presenting with jaundice, two patients were palliated by interventional endoscopy. CONCLUSIONS: For hepatectomy requiring a short resection of the bile duct or for high bile duct injury during complex hepatectomy, a tension-free, well-vascularized duct-to-duct reconstruction over a stent is a suitable option that offers good oncological clearance of the bile duct and satisfactory functional results. PMID- 22037691 TI - Accuracy of axillary ultrasound in the diagnosis of nodal metastasis in invasive breast cancer: a review. AB - Axillary lymph node status is the most important prognostic factor in early-stage breast cancer. Sentinel lymph node biopsy is used to determine the need for axillary node dissection. This technique incurs cost associated with radio isotope administration and use of the operating room. Accordingly, there is a need to preoperatively identify patients with nodal metastases who can proceed directly to axillary dissection. Axillary ultrasound has increasingly been used to determine nodal status prior to surgery. It has been shown to be a sensitive and specific modality in the detection of nodal metastases. When combined with fine-needle aspiration, the specificity of this modality significantly increases. Here we present a current review of the usefulness of preoperative axillary ultrasound in early and locally advanced breast cancer patients with and without fine-needle aspiration biopsy. Based on this review, we estimate the proportion of patients that can be spared a sentinel lymph node biopsy and the concomitant benefit of axillary ultrasound in terms of cost. PMID- 22037692 TI - Impact of advanced age on outcomes following damage control interventions for trauma. AB - BACKGROUND: Damage control (DC) strategy has significantly contributed to mortality reduction in massively bleeding and critically injured trauma victims. However, there is a lack of literature validating the effectiveness of this approach in the elderly population. METHODS: The trauma registry of a Level I trauma center was utilized to identify all severely injured patients [Injury Severity Score (ISS) >=16] from January 1996 to December 2007 who underwent initial DC procedures. Patients with a head Abbreviated Injury Scale (AIS) >=3 were excluded from the analysis. Demographics, clinical and physiological parameters, and in-hospital outcome measures were compared between elderly (>=55 years) and younger (<55 years) patient cohorts subjected to DC procedures. RESULTS: Overall, 158 patients met the inclusion criteria. Among them, 34 patients (21.5%) were aged >=55 years (range 55-85 years) and 124 patients (78.5%) were <55 years old (range 16-54 years). The overall in-hospital mortality rate was 10.1% (n = 16) with a significantly higher mortality rate for elderly patients than for younger patients: 29.4% vs. 4.8%; adjusted P = 0.001; adjusted odds ratio (OR) with 95% confidence interval (CI) 7.09 (2.30-21.74). When stratified by DC subgroups, the case-fatality rate was significantly higher for the elderly patients who underwent extremity DC procedures [19.2% vs. 3.2%; adjusted P = 0.032; adjusted OR with 95% CI 5.95 (1.16-30.30)] and DC laparotomy [55.6% vs. 7.1%; P = 0.005; OR and 95% CI 16.25 (2.32-114.06)]. Both cohorts required massive transfusion during the initial 24 h of admission (18.9 +/- 2.9 vs. 15.1 +/- 1.6 units of packed red blood cells; P = 0.290). Nevertheless, there were no statistically significant differences between the two groups regarding hospital and surgical intensive care unit lengths of stay or major in-hospital complications. CONCLUSIONS: The mortality rate for elderly trauma patients undergoing DC is excessive at 29%. Despite the significant burden of injury and the massive transfusion requirement, most of the elderly patients subjected to DC survived and experienced in-hospital morbidity measures comparable to those of the younger patients. Our results provide further support for damage control intervention in severely injured elderly patients. PMID- 22037693 TI - Targeting angiogenesis in gastroesophageal cancer: industry-sponsored trials are not the answer. PMID- 22037694 TI - Transgenic nematodes as biosensors for metal stress in soil pore water samples. AB - Caenorhabditis elegans strains carrying stress-reporter green fluorescent protein transgenes were used to explore patterns of response to metals. Multiple stress pathways were induced at high doses by most metals tested, including members of the heat shock, oxidative stress, metallothionein (mtl) and xenobiotic response gene families. A mathematical model (to be published separately) of the gene regulatory circuit controlling mtl production predicted that chemically similar divalent metals (classic inducers) should show additive effects on mtl gene induction, whereas chemically dissimilar metals should show interference. These predictions were verified experimentally; thus cadmium and mercury showed additive effects, whereas ferric iron (a weak inducer) significantly reduced the effect of mercury. We applied a similar battery of tests to diluted samples of soil pore water extracted centrifugally after mixing 20% w/w ultrapure water with air-dried soil from an abandoned lead/zinc mine in the Murcia region of Spain. In addition, metal contents of both soil and soil pore water were determined by ICP MS, and simplified mixtures of soluble metal salts were tested at equivalent final concentrations. The effects of extracted soil pore water (after tenfold dilution) were closely mimicked by mixtures of its principal component ions, and even by the single most prevalent contaminant (zinc) alone, though other metals modulated its effects both positively and negatively. In general, mixtures containing similar (divalent) metal ions exhibited mainly additive effects, whereas admixture of dissimilar (e.g. trivalent) ions often resulted in interference, reducing overall levels of stress-gene induction. These findings were also consistent with model predictions. PMID- 22037695 TI - Fundulus heteroclitus adapted to PAHs are cross-resistant to multiple insecticides. AB - Atlantic killifish (Fundulus heteroclitus) from the Atlantic Wood Superfund site on the Elizabeth River (ER), VA are dramatically resistant to the acute toxicity and teratogenesis caused by polycyclic aromatic hydrocarbons (PAHs). To understand the consequences of adaptation to chronic PAH pollution, we have attempted to further define the chemical tolerance associated with this resistance. An important component of the PAH adaptation of ER fish is the dramatic down-regulation of the aryl hydrocarbon receptor (AHR) pathway, resulting in decreased cytochrome p450 (CYP) 1 activity. Herein, we compared the susceptibility to several insecticides of ER fish to that of reference site (King's Creek; KC) fish; use of these chemicals as probes of the resistance will help to demonstrate if the contaminant adaptation exhibited by ER fish is broad or narrow and AHR-focused. We hypothesized that ER fish would be less susceptible to the organophosphate chlorpyrifos (activated by CYP) and more susceptible to the pyrethroid permethrin (detoxified by CYP). Comparison of acute toxicity in 5 day-old larvae supported this hypothesis for chlorpyrifos. As expected, chemical up-regulation of CYP by co-exposure to beta-naphthoflavone (BNF) enhanced the susceptibility of KC but it did not affect ER larvae. Unexpectedly, ER larvae were much less susceptible to permethrin than KC larvae. However, co-exposure to BNF greatly decreased the susceptibility of KC larvae, indicating that metabolism of permethrin by CYP was protective. Additionally, fish from each population were compared for susceptibility to the carbamate carbaryl, an acute neurotoxicant and weak AHR agonist that induces teratogenesis similar to that caused by PAHs. ER embryos and larvae were less susceptible than KC fish. These results suggest that the adaptive phenotype of ER fish is multi-faceted and that aspects other than CYP response are likely to greatly affect their response to contaminants. PMID- 22037696 TI - Burst firing transitions in two-compartment pyramidal neuron induced by the perturbation of membrane capacitance. AB - Neuronal membrane capacitance C (m) is one of the prominent factors in action potential initiation and propagation and then influences the firing patterns of neurons. Exploring the roles that C (m) plays in different firing patterns can facilitate the understanding of how different factors might influence neuronal firing behaviors. However, the impacts of variations in C (m) on neuronal firing patterns have been only partly explored until now. In this study, the influence of C (m) on burst firing behaviors of a two-compartment pyramidal neuron (including somatic compartment and dendritic compartment) was investigated by means of computer simulation, the value of C (m) in each compartment was denoted as C (m,s) and C (m,d), respectively. Two cases were considered, in the first case, we let C (m,s) =C (m,d), and then changed them simultaneously. While in the second case, we assumed C (m,s) ?C (m,d), and then changed them, respectively. From the simulation results obtained from these two cases, it was found that the variation of C (m) in the somatic compartment and the dendritic compartment show much difference, simulated results obtained from the variation of C (m,d) have much more similarities than that of C (m,s) when comparing with the results obtained in the first case under which C (m,s) =C (m,d). These different effects of C (m,s) and C (m,d) on neuronal firing behaviors may result from the different topology and functional roles of soma and dendrites. Numerical results demonstrated in this paper may give us some inspiration in understanding the possible roles of C (m) in burst firing patterns, especially their transitions in compartmental neurons. PMID- 22037697 TI - Cardiac fibrillation risk of TASER X-26 dart mode application. AB - In view of reported fatalities there are still controversial discussions on whether electronic stun law enforcement weapons can cause cardiac fibrillation. Experimental data are contradictory. Simplified theoretical estimations led to a negligible low risk of 8.10(-7). With a detailed numerical-anatomical model of an adult man (NORMAN) cardiac exposure to Taser X26 high-tension pulses was quantitatively assessed and the fibrillation risk estimated by accounting for its dependence on excited volume based on 3D cardiac exposure patterns. For distance mode and worst case dart hits it could be demonstrated that cardiac exposure can reach the 30% fibrillation risk level. Risk reduces considerably if direct current flow across the heart is prevented. The overall fibrillation risk of Taser application is further reduced by the limited probability of critical hits. However, in agreement with experimental findings it is demonstrated that cardiac fibrillation risk of Taser X26 dart mode application is small, however, not negligible. PMID- 22037698 TI - A chimeric chromosome in the ciliate oxytricha resulting from duplication. AB - In a process similar to exon splicing, ciliates use DNA splicing to produce a new somatic macronuclear genome from their germline micronuclear genome after sexual reproduction. This extra layer of DNA rearrangement permits novel mechanisms to create genetic complexity during both evolution and development. Here we describe a chimeric macronuclear chromosome in Oxytricha trifallax constructed from two smaller macronuclear chromosomes. To determine how the chimera was generated, we cloned and sequenced the corresponding germline loci. The chimera derives from a novel locus in the micronucleus that arose by partial duplication of the loci for the two smaller chromosomes. This suggests that an exon shuffling-like process, which we call MDS shuffling, enables ciliates to generate novel genetic material and gene products using different combinations of genomic DNA segments. PMID- 22037699 TI - Supramolecular hydrogelators of N-terminated dipeptides selectively inhibit cancer cells. AB - Consisting of N-terminated diphenylalanine, a new type of supramolecular hydrogelators forms hydrogels within a narrow pH window (pH 5.0 to 6.0) and selectively inhibits growth of HeLa cells, which provides important and useful insights for designing molecular nanofibers as potential nanomedicines. PMID- 22037700 TI - Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-gamma. AB - We previously reported that Trypanosoma cruzi, the agent of Chagas disease, induces in congenitally infected fetuses a strong, adult-like parasite-specific CD8(+) T cell response producing IFN-gamma (Hermann et al. in Blood 100:2153 2158, 2002). This suggests that the parasite is able to overcome the immaturity of neonatal antigen presenting cells, an issue which has not been previously addressed. We therefore investigated in vitro the ability of T. cruzi to activate cord blood DCs and compared its effect to that on adult cells. We show that T. cruzi induces phenotypic maturation of cord blood CD11c(+) myeloid DCs (mDCs), by enhancing surface expression of CD40, CD80, and CD83, and that parasite-specific IgG purified from cord blood of neonates born to T. cruzi-infected mothers amplify such expression. CD83, considered as the best marker of mature DCs, reaches higher level on cord blood than on adult mDCs. Allo-stimulation experiments showed that T. cruzi-activated cord blood mononuclear cells enriched in DCs (eDCs) stimulate proliferation of cord blood and adult CD3(+) T cells to a similar extent. Of note, T. cruzi-activated eDCs from cord blood trigger more potent proliferation of CD8(+) than CD8(-) (mainly CD4(+)) adult T cells, a feature not observed with adult eDCs. T cell proliferation is associated with IFN gamma release and down-regulation of IL-13 production. These data show that T. cruzi potently activates human cord blood mDCs and endows eDCs to trigger CD8(+) T cell proliferation and favor type 1 immune response. Interestingly, maternal antibodies can strengthen the development of mature DCs that might contribute to overcome the immunological immaturity associated with early life. PMID- 22037701 TI - Skin conductance for monitoring of acute pain in adult postoperative patients: influence of electrode surface area and sampling time. AB - Aim of this prospective randomized study was to determine the influence of the electrode surface area and sampling time on the accuracy of the number of fluctuations in skin conductance per second to distinguish different states of acute pain. These methodological issues have been previously suggested as an explanation for contradictory data related to the accuracy of the skin conductance monitor. A total of 541 pain ratings on a numeric rating scale (0-10) were obtained from 120 adult postoperative patients. The number of fluctuations in skin conductance per second was recorded using two different electrode types (surface area 254 vs. 474 mm(2)) and sampling times (7.5 vs. 30 s). A longer sampling time did result in higher values for the number of fluctuations in skin conductance per second, though without improving its accuracy to distinguish different states of pain. However, the latter was found improved when the smaller surface area electrodes were used. A combination of small surface area electrodes and a 30 s sampling time resulted in the highest area under the curve in the receiver operating curve analysis of the method to identify states of moderate to severe pain (numeric rating scale > 3): 0.68 vs. e.g. 0.55 [data from all patients combined]). We conclude that the type of electrodes used but only to a lesser degree the sampling time influence the accuracy of the number of fluctuations in skin conductance per second to identify states of moderate or severe postoperative pain. PMID- 22037702 TI - Yeast one-hybrid assays for gene-centered human gene regulatory network mapping. AB - Gateway-compatible yeast one-hybrid (Y1H) assays provide a convenient gene centered (DNA to protein) approach to identify transcription factors that can bind a DNA sequence of interest. We present Y1H resources, including clones for 988 of 1,434 (69%) predicted human transcription factors, that can be used to detect both known and new interactions between human DNA regions and transcription factors. PMID- 22037703 TI - Automated protein-DNA interaction screening of Drosophila regulatory elements. AB - Drosophila melanogaster has one of the best characterized metazoan genomes in terms of functionally annotated regulatory elements. To explore how these elements contribute to gene regulation, we need convenient tools to identify the proteins that bind to them. Here we describe the development and validation of a high-throughput yeast one-hybrid platform, which enables screening of DNA elements versus an array of full-length, sequence-verified clones containing over 85% of predicted Drosophila transcription factors. Using six well-characterized regulatory elements, we identified 33 transcription factor-DNA interactions of which 27 were previously unidentified. To simultaneously validate these interactions and locate the binding sites of involved transcription factors, we implemented a powerful microfluidics-based approach that enabled us to retrieve DNA-occupancy data for each transcription factor throughout the respective target DNA elements. Finally, we biologically validated several interactions and identified two new regulators of sine oculis gene expression and hence eye development. PMID- 22037704 TI - Visualizing mechanical tension across membrane receptors with a fluorescent sensor. AB - We report a fluorescence-based turn-on sensor for mapping the mechanical strain exerted by specific cell-surface proteins in living cells. The sensor generates force maps with high spatial and temporal resolution using conventional fluorescence microscopy. We demonstrate the approach by mapping mechanical forces during the early stages of regulatory endocytosis of the ligand-activated epidermal growth factor receptor (EGFR). PMID- 22037705 TI - Enhanced yeast one-hybrid assays for high-throughput gene-centered regulatory network mapping. AB - A major challenge in systems biology is to understand the gene regulatory networks that drive development, physiology and pathology. Interactions between transcription factors and regulatory genomic regions provide the first level of gene control. Gateway-compatible yeast one-hybrid (Y1H) assays present a convenient method to identify and characterize the repertoire of transcription factors that can bind a DNA sequence of interest. To delineate genome-scale regulatory networks, however, large sets of DNA fragments need to be processed at high throughput and high coverage. Here we present enhanced Y1H (eY1H) assays that use a robotic mating platform with a set of improved Y1H reagents and automated readout quantification. We demonstrate that eY1H assays provide excellent coverage and identify interacting transcription factors for multiple DNA fragments in a short time. eY1H assays will be an important tool for mapping gene regulatory networks in Caenorhabditis elegans and other model organisms as well as in humans. PMID- 22037706 TI - Enhanced Y1H assays for Arabidopsis. AB - We present an Arabidopsis thaliana full-length transcription factor resource of 92% of root stele-expressed transcription factors and 74.5% of root-expressed transcription factors. We demonstrate its use with enhanced yeast one-hybrid (eY1H) screening for rapid, systematic mapping of plant transcription factor promoter interactions. We identified 158 interactions with 13 stele-expressed promoters, many of which occur physically or are regulatory in planta. PMID- 22037708 TI - A new flow control technique using diluted epinephrine in the N-butyl-2 cyanoacrylate embolization of visceral artery pseudoaneurysms secondary to chronic pancreatitis. AB - Although n-butyl-2-cyanoacrylate (NBCA) has been used as an effective liquid embolization material, its indication for pseudoaneurysms has seemingly been limited because of the technical difficulties of using NBCA, such as reflux to the parent artery and causing significant infarction. Thus, considerable skill in using NBCA or a device to control blood flow during its polymerization is required to achieve embolization without severe complications. We report our new technique for controlling blood flow using diluted epinephrine in transcatheter arterial NBCA embolization of five pseudoaneurysms in four cases secondary to hemosuccus pancreaticus. PMID- 22037707 TI - Fabry disease, enzyme replacement therapy and the significance of antibody responses. AB - Fabry disease is an X-linked disorder caused by a deficiency of alpha galactosidase A. This leads to a progressive accumulation of globotriaosylceramide in tissues throughout the body. Cardiac, renal and neurological manifestations are common and life expectancy is significantly reduced relative to the general population. Management of Fabry disease involves the administration of intravenous enzyme replacement therapy (ERT). Two forms - agalsidase alfa and agalsidase beta - have been licensed in certain jurisdictions and are generally well tolerated; however, some patients develop antibodies to the infused enzyme, which may impair the efficacy and safety of treatment. Agalsidase alfa and agalsidase beta are produced in different systems; this leads to certain differences in post-translational modification that may affect immunogenicity. Immunoglobulin (Ig) G antibodies have frequently been reported in patients with Fabry disease receiving ERT; IgG responses are reported in a greater proportion of patients receiving agalsidase beta than in patients receiving agalsidase alfa. IgE antibodies are less common than IgG antibodies, and have not been observed in patients receiving agalsidase alfa. However, these data are difficult to interpret due to methodological differences in the assessment of seropositivity, and in the doses of enzyme used. The clinical impact of the development of IgG antibodies to ERT in patients with Fabry disease remains unclear, due to lack of data and to the marked heterogeneity of patients both in terms of disease manifestations and response to therapy. Further studies that examine the development of antibodies in patients with Fabry disease and the potential impact of such antibodies on the outcome of ERT are necessary. PMID- 22037709 TI - Hepatic toxicity after radioembolization of the liver using (90)Y-microspheres: sequential lobar versus whole liver approach. AB - PURPOSE: (90)Y-radioembolization (RE) is a promising technique for delivering high doses of radiation to liver tumors but may result in compromise of liver function. To gain further perspective, we evaluated the toxicity rates of sequential lobar versus "whole liver" (90)Y-radioembolization. METHODS: Thirty four patients with liver malignancy in noncirrhotic livers were included; (90)Y radioembolization was performed as either whole liver or sequential lobar treatment in 17 patients each. Standard clinical and liver specific laboratory parameters as well as MR imaging before treatment and at follow-up (6 and 12 weeks) after radioembolization were evaluated for toxicity using the Common Terminology Criteria for Adverse Events (CTCAE). Volumetry of the liver, tumor, and spleen and measurement of portal vein diameter also were performed. RESULTS: Three months after whole liver RE, 14 liver-related grade 3/4 events were recorded versus 2 events after sequential lobar treatment (P < 0.05). Three patients treated with whole liver RE suffered from radioembolization-induced liver disease (REILD). Pathological increases in bilirubin at 3 months were observed for the whole liver group only (52.3 vs. 18.7 MUmol/l, P = 0.012). Total liver volume did not change significantly in either group, but shrinkage of the initially treated hepatic lobe with compensatory hypertrophy of the subsequently treated lobe was observed in the sequential lobar group (P < 0.05). Portal vein diameter increased significantly in whole liver-treated patients only (+17% vs. +6.6%, P = 0.043). CONCLUSIONS: Noncirrhotic patients undergoing sequential lobar radioembolization had less hepatic toxicity compared to whole liver embolization. The sequential approach should be the preferred strategy. PMID- 22037710 TI - Scanned proton radiotherapy for mobile targets-the effectiveness of re-scanning in the context of different treatment planning approaches and for different motion characteristics. AB - The most advanced delivery technique for proton radiotherapy is active spot scanning. So far, predominantly static targets have been treated with active spot scanning, since mobile targets in combination with dynamic treatment delivery can lead to interplay effects, causing inhomogeneous dose distributions. One way to mitigate motion effects is re-scanning. In this study we investigate the effectiveness of re-scanning in relation to different plan parameters (number of fields, field directions, number of re-scans) as well as in respect to different motion parameters (motion amplitude, motion starting phase). A systematic study was performed for three liver patients, for which ten different plans have been calculated, respectively. The treatment plans were evaluated for three different scenarios (static, motion/single-scan-delivery, motion/re-scanned-delivery). The choice of motion parameters was based on an evaluation of the 4D CT data sets of the three patients. It is shown that the effect of motion/re-scanning per fraction is largest the fewer fields per plan are used and the more the field direction differs from the main motion direction. For amplitudes up to 6 mm, re scanning may not be required if multiple fields are used, since only dose blurring effects appear that cannot be compensated by re-scanning. For larger motion amplitudes two planning strategies are proposed. PMID- 22037711 TI - Successful pulmonary valvuloplasty in combined pulmonary valve stenosis and selective left pulmonary artery ectasia. PMID- 22037712 TI - Polypoid atrial myxoma. AB - Myxomas are by far the most common tumours of the heart. A 75-year-old man with no notable medical history presented with a 2-month progressive weight loss and dyspnoea on exertion. Physical examination revealed an opening snap and a diastolic decrescendo murmur at the apex. Transthoracic echocardiography showed a large, 85 * 30 mm, mobile, polypoid mass arising from the atrial fossa ovalis and protruding into the left ventricle during diastole. Irregular shape, multilobated surface and soft-tissue echogenicity were consistent with emboligenic myxoma. Surgical inspection confirmed a reddish gelatinous myxoma with villous, friable, thrombus-like surface prone to embolize. The mass was successfully removed and the histologic report confirmed the diagnosis.At 3-year follow-up, the patient is asymptomatic and no further mass has been detected. The case confirms that echocardiography remains a primary tool for the assessment of cardiac masses, providing morphological clues to define the potential risk of complications such as valve obstruction and systemic embolization. PMID- 22037713 TI - Is cardiac rehabilitation still relevant in the new millennium? AB - Cardiac rehabilitation is an evidence-based intervention which has evolved over time and incorporates physical, psycho-social and educational components with the aim of improving the patients' functioning following a cardiac event. The evidence base for cardiac rehabilitation following acute myocardial infarction has been growing over the past half a century. Individual randomized control trials were small and, therefore, mortality outcomes usually failed to reach significance; however, meta-analyses have proven consistently that participation in cardiac rehabilitation following a myocardial infarction is associated with a significant improvement in mortality. In the era of revascularization and improved drug therapies, observational studies still provide evidence that independent of other treatments, cardiac rehabilitation is a life-saving measure. Although early studies often only studied young males, more contemporary data include patients from all sectors of society and have found that groups such as women, the elderly and those with heart failure appear to have greater mortality benefits compared with the traditional young male cohort. Uptake remains a problem and one challenge for the future is ensuring improved uptake on to good quality rehabilitation programmes and demonstrating these positive effects. PMID- 22037714 TI - Expression of genes related to multiple drug resistance and apoptosis in acute leukemia: response to induction chemotherapy. AB - Resistance to chemotherapy is a major impediment to the successful treatment of acute leukemia (AL). Expression of genes involved in drug resistance and apoptosis may be responsible for this. This study aimed to investigate the expression of drug resistance (MDR1, MRP1, LRP, BCRP, GSTP1, DHFR) and apoptotic genes (p53, BCL-2, Survivin) in adult acute leukemias and compare them with clinical and hematological findings and response to induction chemotherapy. Eighty-five patients with AL [45 with acute myeloid leukemia (AML) and 40 with acute lymphoblastic leukemia (ALL)] were used as a study group. Real-time PCR results showed that expression level of MDR1 was significantly higher in AML whereas expression of DHFR, BCRP and Survivin was significantly higher in ALL patients. In AML, significant correlation was observed between LRP and MRP1 (r(s)=0.44, p=0.016), LRP and DHFR (r(s)=0.41, p=0.02), MDR1 and BCL-2 (r(s)=0.38, p=0.03). Expression of GSTP1 and LRP correlated with high white blood count (p=0.03 and p=0.03) and BCL-2 with high peripheral blast count (p=0.009). MDR1 expression was significantly associated with the expression of immature stem cell marker CD34 (p=0.002). In ALL, significant association was found between LRP gene and female sex (p<0.0001), LRP and B-ALL patients (p=0.04) and LRP and BCR/ABL positive patients (p=0.004). High expression of MDR1 and BCL-2 in AML and MRP1 gene in ALL was associated with response to induction chemotherapy (p=0.001, p=0.02 and p=0.007 respectively). These results showed the potential clinical relevance of MDR1, MRP1 and BCL-2 in adult patients with acute leukemia in the context of induction chemotherapy. PMID- 22037715 TI - The diazofluorene antitumor antibiotics: structural elucidation, biosynthetic, synthetic, and chemical biological studies. AB - This review presents a comprehensive survey of all aspects of the kinamycins and lomaiviticins, potent antiproliferative antimicrobial metabolites isolated from various strains of Streptomyces and Salinispora. The kinamycins and lomaiviticins contain a diazotetrahydrobenzo[b]fluorene (diazofluorene) functional group, which is unique among known natural products. This review begins with an account of the studies leading to the final (correct) structure determination of the kinamycins, which were originally proposed to contain an N-cyano carbazole function. This is followed by a discussion of biosynthetic studies, which established the polyketide nature of the kinamycins. Descriptions of four completed syntheses of various kinamycins, synthetic studies toward the lomaiviticins, syntheses of the carbohydrates of the lomaiviticins, and syntheses of structurally-related metabolites, are then presented. A survey of chemical biological investigations, including in vitro reactivity studies, which indicate that the kinamycins and lomaiviticins may form reactive ortho-quinone methide or free radical intermediates in vivo, is presented. Finally, a selection of structurally-related metabolites are described. PMID- 22037716 TI - Soluble triggering receptor expressed on myeloid cells in severe acute pancreatitis: a biological marker of infected necrosis. AB - PURPOSE: The diagnosis and treatment of secondary infection of pancreatic necrotic tissue remain a major challenge. The level of soluble triggering receptor expressed on myeloid cells (sTREM-1) in fine needle aspiration (FNA) fluid may be a good marker of infected necrosis. METHODS: Patients with a clinical suspicion of secondary infection of necrotic tissue were enrolled. The serum levels of C-reactive protein, amylase, procalcitonin (PCT), and sTREM-1 and the fluid levels of sTREM-1, PCT, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and amylase were examined. When infected necrosis was defined, the first step was percutaneous or endoscopic drainage. If there was no improvement after 72 h, an open necrosectomy was performed. RESULTS: In 30 patients with suspected infection, 18 patients were diagnosed as having secondary infection of necrotic tissue. The levels of sTREM-1 and PCT in FNA fluid were found to have the closest correlation with the diagnosis of infected necrosis [sTREM-1: area under the receiver operating characteristic curve (AUC) 0.972; 95% confidence interval (95%CI) 0.837-1.000; PCT: AUC 0.903; 95%CI 0.670-0.990, P > 0.05]. A fluid sTREM-1 cutoff value of 285.6 pg/ml had a sensitivity of 94.4% and a specificity of 91.7%. In a multiple logistic regression analysis, an sTREM-1 level of more than 285 pg/ml and a PCT level of more than 2.0 ng/ml in FNA fluid were independent predictors of infected necrosis. CONCLUSIONS: The fluid level of sTREM-1 will help in the rapid and accurate diagnosis of secondary infection of necrotic tissue in patients with severe acute pancreatitis (SAP). PMID- 22037717 TI - [Preoperative risk evaluation from the perspective of anaesthesiology]. AB - Medical and technical progress together with demographic changes has led to a more complex perioperative care for patients. Accordingly, an optimal preoperative assessment in particular an adequate risk evaluation is more important than ever. A recently published joint recommendation of the German Society of Anaesthesiology and Intensive Care Medicine, the German Society of Surgery and the German Society of Internal Medicine aims to reduce considerable uncertainties in the preoperative risk evaluation especially with regard to"technical tests" by providing transparent and comprehensive arrangements. Consequently, routine screening will be abandoned in favour of targeted patient and operation-oriented individual risk assessment. This approach will change the preoperative risk evaluation in a scientific, organisational and economic way. The following article on preoperative risk evaluation is based on the valuable and helpful recommendation and aims to provide additional important aspects from the perspective of anaesthesiologists. PMID- 22037718 TI - The comparison of bacteremia and amount of bleeding during septoplasty. AB - The aim of this study was to investigate the relationship between the amount of bleeding and bacteremia during nasal septal surgery. Seventy-one patients undergoing septoplasty were enrolled in the present study. The amount of bleeding was measured and recorded for each patient. Preoperative and postoperative blood cultures were collected immediately after the induction of anesthesia and 20 min after the operation, respectively. While none of the blood cultures taken preoperatively were positive for any organism, the cultures obtained postoperatively were positive in 9 (12.7%) of 71 patients who underwent septoplasty, and bacteremia was more frequent among those with a greater amount of bleeding during the surgery. The results of this study suggest that although bacteremia had no clinical consequences for patients, patients with more bleeding have an increased risk of developing bacteremia which may cause complications in higher risk individuals. PMID- 22037719 TI - Audio-vestibular evaluation in patients with essential tremor. AB - The aim of this study was to investigate audio-vestibular function in patients with essential tremor. Twenty-three patients with essential tremor (46 ears) and 21 health control subjects (42 ears) were included in the present study. Patients and comparison subjects were matched for age and gender. All patient and control subjects underwent pure tone audiometric test, tympanogram, transient-evoked otoacoustic emissions and auditory brainstem response. Vestibular system was evaluated by bitermal caloric test. Comparison of variables between the groups was performed. Investigation of the relationship between parameters about ET disease and hearing levels were also studied. Pure tone thresholds significantly differed between patients and controls in 250 and 500 Hz frequencies (p < 0.05). There was no statistically significant difference in 1,000, 2,000, 4,000, and 6,000 Hz frequencies in essential tremor patients in comparison to the control subjects. A correlation between tremor severity and audiometric scores in low frequencies was not found. In addition, statistical analysis did not demonstrate a correlation between audiometric scores and tremor duration. The otoacoustic emission responses were found significantly different in patient and control group. The latencies of waves I, V and I-V inter-peak latencies on the ABR were not different between the groups. Our findings indicated that, abnormalities are due to cochlea rather than the retro cochlear pathology which is responsible for hearing loss associated with essential tremor. PMID- 22037720 TI - Who ends up having tonsillectomy after peritonsillar infection? AB - We wanted to explore how many patients will undergo tonsillectomy during the first 5 years after peritonsillar abscess or peritonsillar cellulitis, and why. In addition we sought predictive factors as to who would benefit from tonsillectomy. Medical records of 809 patients with peritonsillar infection (ICD 10 J36) aged over six were analyzed, and data on the history of tonsil infections and differences in treatment were collected. Data on patients who underwent tonsillectomy during the next 5 years were compared with data on patients needing no tonsillectomy. An abscess or planned interval tonsillectomy was performed on 159 patients. Of the conservatively treated 7- to 16.9-year-old patients, 42.5% required surgery later, of those aged 17-29.9 years, 31.3%, and those over 30, 13.2% (p < 0.001). Previous tonsillar infections led to increased (p = 0.067) probability of delayed tonsillectomy. Re-opening of the abscess cavity at the polyclinics, use of broad-spectrum antibiotics in the acute phase of infection, or being an outpatient or inpatient had no influence on the probability of later surgery. Overall one-fourth of the patients with peritonsillar infection underwent tonsillectomy during the next 5 years, even without being originally planned. Young age and previous tonsillar infections caused increased probability of delayed tonsillectomy. PMID- 22037721 TI - The relationship between the Epworth Sleepiness Scale and polysomnographic parameters in obstructive sleep apnea patients. AB - The aim of this study was to investigate the relationship between the subjective Epworth Sleepiness Scale (ESS) and objective polysomnographic parameters that was compared in dichotomized groups of obstructive sleep apnea (OSA) patients with and without excessive daytime sleepiness (EDS). A retrospective review of the 96 consecutive snoring patients suspected of OSA due to upper airway problems was performed. ESS score was assessed and EDS was considered present when the ESS score was >10. Polysomnography was performed for each patient. Comparisons of polysomnographic parameters between both groups of patients were performed using Mann-Whitney U-tests. The Pearson's correlation coefficient was calculated. EDS patients showed significantly greater body mass index (BMI), AHI and ODI, higher percentage of snoring time, a longer time length of SpO(2) < 90% and lower minimum SpO(2) compared to no EDS patients. There was no statistical difference in other sleep parameters. A positive correlation between the ESS score and BMI, percentage of snoring time, minimum SpO(2) and time length of SpO(2) < 90% was identified. Despite many controversies, our conclusion is that apnea/hypoxemia has considerable coherence to account for the EDS measured by ESS in OSA patients. PMID- 22037722 TI - Efficacy of a topical suspension of bacterial antigens for the management of chronic suppurative otitis media. AB - The aim of this study was to compare the efficacy and safety of a topical suspension of bacterial antigens for the management of chronic suppurative otitis media (CSOM). Two-hundred ten patients with CSOM were enrolled in this study. The patients were divided into two numerically equal groups and randomized to receive a topical suspension of bacterial antigens, Lantigen B (group A), or placebo (group B), according to the following protocol: 5 drops thrice a day for 12 consecutive weeks in the external acoustic duct. The topical suspension of bacterial antigens and placebo were administered by identical, anonymous dispensers in order to maintain double-blind conditions. Before, at the end and 3 months, and after the end of the treatment, all patients who entered in the study underwent pure tone audiometry, microscopic examination of ears, microbiological examination of the ear swab, aural suctioning and subjective assessment of symptoms by visual analog scale. In group A, we saw a statistically significant improvement in the different items measured. A topical suspension of bacterial antigens was significantly more effective than placebo in the treatment of CSOM. PMID- 22037723 TI - Prevalence of GBJ2 mutations in patients with severe to profound congenital nonsyndromic sensorineural hearing loss in Bulgarian population. AB - Objective of the study is to assess the prevalence of Connexin 26 (GJB2) mutation in patients with congenital nonsyndromic sensorineural hearing loss in Bulgarian population. Study design is done prospectively. Patient inclusion criteria for this study were diagnosis of congenital nonsyndromic hearing loss, and absence of potential sibling relationships between patients included in the study (anamnestic pedigree for at least three generations). Patients were excluded from the study group if one of the following conditions were present: secondary hearing loss (cytomegalovirus, rubella, meningo-encephalitis, mastoiditis, other infections, posterior fossa tumors, etc.), exposure to drugs or other prenatal or perinatal etiology of deafness, and congenital syndromic hearing loss. Genomic DNA samples from whole blood were tested with sequence analysis for mutations in the coding region of the GJB2. Results state that 51 patients were analyzed for GJB2 mutations. Twenty of the patients (39%) with mutant alleles were homozygous for the c.35delG mutation (c.35delG/c.35delG) and four patients (8%) presented as heterozygotes (c.35delG/WT). In one patient, who carried a heterozygous mutation c.35delG, a second mutation was found-312del114. Additionally, in two other patients were discovered the mutations Trp24X (W24X) and, respectively, Arg127His(R127H), both in heterozygous states. From the whole study group there was only one patient with compound heterozygous genotype p.Leu90Pro(L90P)/p.Ile121Asn. The latter one has never been reported in the literature so far. In conclusion, this study determines the importance of connexin 26 mutations in Bulgarian children with severe to profound congenital nonsyndromic sensorineural hearing loss, the prevalence of the different mutation variants and their relationship with the ethnical background of the patients. In addition, we report for the first time a novel mutation in the GJB2 gene. PMID- 22037724 TI - [Recommendations for acute treatment for chemical and thermal burns of eyes and lids]. AB - With these recommendations the authors want to improve the acute therapy of eye burns based on the literature and clinical experience. Due to the lack of studies with high evidential value we base these recommendations on the results of experimental work and reports of successfully treated eye burns. A development of this document by systematic research is necessary. Despite the limited knowledge, the collated facts are the current state of the art of treatment according to the knowledge and research of the authors. The most important clinical recommendation is to rinse a chemically or thermally burnt eye as soon and as extensively as possible. Any delay worsens the prognosis. Substances on the market for first aid have different levels of clinical evidence. Thus saline and amphoteric diphoterine have been evaluated in a prospective clinical study showing an advantage for the amphoter. Water, borate buffer, phosphate buffers and derivatives have never been proven to work in clinical applications. Nevertheless, they are recommended. Within experimental work in vitro we could show the value of polyvalent decontamination. Side-effects of phosphate buffers have been demonstrated in retrospective clinical and prospective experimental studies so that even in cases of beneficial effects on pH we cannot recommend these substances which propagate corneal calcification. Special types of burns, such as hydrofluoric acid need special treatment but as clinical studies are lacking only experimental data can offer suitable recommendations. PMID- 22037725 TI - [Chemical and thermal eye burns. Conservative and surgical options of a stage dependent therapy]. AB - The basic principles of first aid for chemical and thermal burns are discussed. In the acute phase the primary goal of all measurements is the prevention or limitation of tissue destruction. The further therapeutic care is focused on the modulation of the inflammatory response, the prevention of a bacterial infection and secondary glaucoma and the stimulation of wound healing. The individual concept of measures to be taken is recruited from the careful identification of necrotic tissue, the eye burn classification of severity and on the basis of all described medical and surgical therapy options. In the case of severe and very severe ocular burns a comprehensive surgical reconstruction is included. All outpatient departments and eye clinics taking part on the treatment have to ensure a standardized complete and scientifically valid therapy regime to restore vision. PMID- 22037726 TI - [Late complications after chemical burns of the ocular surface. Surgical strategies for ocular surface reconstruction]. AB - Severe chemical burns of the ocular surface frequently result in long-standing and ongoing disorders of the conjunctiva and the cornea including conjunctival scarring with shortening of the fornix, cicatricial entropion, complications caused by trichiasis and scarring or chronic ulceration of the cornea. Advanced destruction of limbal stem cells leads to limbal stem cell deficiency with conjunctivalization of the cornea. Surgical therapy aims at the correction of malpositioning of the lids, the reconstruction of the conjunctiva and the fornix utilizing applicable tissue grafts and the reestablishment of a stable, avascular and transparent corneal epithelium by e.g. transplantation of epithelial stem cells. Progressive corneal ulcerations unresponsive to medical therapy can be treated by amniotic membrane transplantation, corneal transplantation or by conjunctival covering depending on the extent of damaged tissue. The surgical therapy of patients after severe chemical burns of the ocular surface is generally performed in specialized centers and occasionally requires a multidisciplinary approach. PMID- 22037728 TI - [Ocular findings in hematological diseases]. AB - Hematological diseases can lead to ocular manifestations in up to 90% of patients and sometimes the ophthalmological findings are the presenting symptom of the disease. The ocular manifestation is often asymptomatic. The diagnosis can be difficult especially when the ocular manifestation represents the first symptoms. In most cases the conjunctiva and retina are involved and are particularly found in patients with anemia, leukemia, Hodgkin and non-Hodgkin lymphoma, myeloproliferative and myelodysplastic syndromes and coagulopathies. Even opportunistic infections in cases of hematological diseases can lead to ocular manifestations. For unexplained retinal alterations with hemorrhage and cotton wool spots an underlying hematological disease should be excluded. PMID- 22037729 TI - Techno-economical efficiency and productivity change of wastewater treatment plants: the role of internal and external factors. AB - Efficiency and productivity are important measures for identifying best practice in businesses and optimising resource-use. This study analyses how these two measures change across the period 2003-2008 for 196 wastewater treatment plants (WWTPs) in Spain, by using the benchmarking methods of Data Envelopment Analysis and the Malmquist Productivity Index. To identify which variables contribute to the sustainability of the WWTPs, differences in efficiency scores and productivity indices for external factors are also investigated. Our results indicate that both efficiency and productivity decreased over the five years. We verify that the productivity drop is primarily explained by technical change. Furthermore, certain external variables affected WWTP efficiency, including plant size, treatment technology and energy consumption. However, plants with low energy consumption are the only ones which improve their productivity. Finally, the benchmarking analyses proved to be useful as management tools in the wastewater sector, by providing vital information for improving the sustainability of plants. PMID- 22037730 TI - Amphiphilic alpha-helical potential: a putative folding motif adding few constraints to protein evolution. AB - Evidence from a number of studies indicates that protein folding is dictated not only by factors stabilizing the native state, but also by potentially independent factors that create folding pathways. How natural selection might cope simultaneously with two independent factors was addressed in this study within the framework of the "Lim-model" of protein folding, which postulates that the early stages of folding of all globular proteins, regardless of their native structure, are directed at least in part by potential to form amphiphilic alpha helices. For this purpose, the amphiphilic alpha-helical potential in randomly ordered amino acid sequences and the conservation in phylogeny of amphiphilic alpha-helical potential within various proteins were assessed. These analyses revealed that amphiphilic alpha-helical potential is a common occurrence in random sequences, and that the presence of amphiphilic alpha-helical potential is present but not conserved in phylogeny within a given protein. The results suggest that the rapid formation of molten globules and the variable behavior of those globules depending on the protein may be a fundamental property of polymers of naturally occurring amino acids more so than a trait that must be derived or maintained by natural selection. Further, the results point toward the utility of randomly occurring process in protein function and evolution, and suggest that the formation of efficient pathways that determine early processes in protein folding, unlike the formation of stable, native protein structure, does not present a substantial hurdle during the evolution of amino acid sequences. PMID- 22037731 TI - Remote ischemic preconditioning protects neurocognitive function of rats following cerebral hypoperfusion. AB - BACKGROUND: Protection of remote ischemic preconditioning on neurocognitive function caused by bilateral common carotid artery occlusion has been investigated in rats. MATERIAL/METHODS: Thirty-six male Sprague-Dawley rats were divided into 3 groups - control group (Group C, n=12), bilateral carotid arteries occlusion group (Group B, n=12) and remote ischemic precondition group (Group P, n=12). In Group P, remote ischemic preconditioning (RIPC) was performed on the right femoral artery with 3 cycles (10 min) of occlusion/perfusion. After 3 cycles of preconditioning, bilateral carotid arteries were occluded immediately for 60 min. In Group B, ischemic insults were conducted without RIPC. Sham surgeries were performed in Group C. Evaluation of memory and learning capacity was performed on days 5-8 after surgery by Morris water maze testing of spatial learning capacity (n=6 for each group). Apoptosis of cells in the hippocampus region was determined by TUNEL tests and Bcl-2 at this region was determined by ELISA 24 h and 9 days after vessel occlusion (n=6 for each group). RESULTS: Neurocognitive tests showed that latency time was significantly longer in Group B than in Group P on day 7 (p=0.016) and day 8 (p=0.036). Moreover, frequency of platform crossings was significant less in group B than in the other 2 groups on day 9. Bcl-2 level was significantly increased in the hippocampal region of rats in Group P on days 1 and 9 after vessel occlusion. TUNEL test showed that apoptosis could be observed at 24 h after occlusion in Group B, but not in Group P and Group C. No apoptosis was observed on day 9. CONCLUSIONS: Our results suggest that RIPC can protect neurocognitive function of rats after bilateral carotid occlusions, and that Bcl-2 may play an important role in this protective effect. PMID- 22037732 TI - Neurotrophin-3 gene transduction of mouse neural stem cells promotes proliferation and neuronal differentiation in organotypic hippocampal slice cultures. AB - BACKGROUND: The transplantation of neural stem cells (NSCs) has been accepted as a promising therapeutic strategy for central nervous system disorders. However, the beneficial effect of NSC transplantation upon functional recovery is limited due to the unfavorable microenvironment (niche) at the site of trauma or degenerative disease in the brain. Combination of transplantation of NSCs with neurotrophins may overcome the hurdles of impaired cell survival and neuronal differentiation. MATERIAL/METHODS: In the current study, the neurotrophin-3 (NT 3) gene was transduced into cultured mouse embryonic cortical NSCs via an AAV vector (NSC-NT-3). The effect of NT-3 over-expression on cell proliferation and differentiation in NSCs was observed by immunohistochemistry, cell culture and organotypic hippocampal slice cultures.
RESULTS: The characteristics of self-renewal and multiple differentiation of NSCs were well-preserved. Cells in the NSC-NT-3 group proliferated faster and differentiated into more beta-tubulin III-positive neurons compared to the control group in vitro. Furthermore, cells in the NSC-NT-3 group survived in a significantly higher percentage and undertook neuronal differentiation preferably in organotypic hippocampal slice cultures. CONCLUSIONS: Our results suggest that the transduction of NT-3 into NSCs could effectively promote NSCs survival, proliferation, and neuronal differentiation in vitro without change of the stemness of NSCs. This work also offers evidence to better understand the safety and efficiency of combined treatment with NT-3 and NSCs for the central nervous system disorders. PMID- 22037733 TI - Nordihydroguaiaretic acid (NDGA) inhibits ritonavir-induced endothelial dysfunction in porcine pulmonary arteries. AB - BACKGROUND: HIV infection and treatment with highly active antiretroviral therapy (HAART) including HIV protease inhibitor ritonavir (RTV) have been associated with endothelial dysfunction and cardiovascular disease including pulmonary arterial hypertension. The objective of this study was to determine if nordihydroguaiaretic acid (NDGA), a natural herbal antioxidant found in the creosote bush Larrea tridentate, can protect vascular tissues against RTV-induced vascular injury. MATERIAL/METHODS: Fresh porcine pulmonary artery (PA) rings were treated with a clinically relevant concentration of RTV (15 umol/L) with or without NDGA for 24 hours, and then subjected to myograph analysis for vasomotor reactivity. Expression of endothelial nitric oxide synthase (eNOS) in both treated PA rings and human pulmonary artery endothelial cells (HPAECs) was analyzed by real-time PCR and immunohistochemistry. Oxidative stress levels were analyzed with the lucigenin-enhanced chemiluminescence and glutathione assay. RESULTS: In response to bradykinin at 10-10 mol/L, RTV-treated PA rings showed a 39% reduction in endothelium-dependent vasorelaxation compared with the control vessels (P<0.05); when co-cultured with NDGA (1.75 or 3.50 umol/L), the relaxation increased by 25% and 48%, respectively. RTV also decreased the maximal contraction and endothelium-independent vasorelaxation in RTV-treated vessels, while NDGA improved these vasomotor responses. In addition, treatment of RTV significantly decreased eNOS mRNA levels in both porcine PAs and HPAECs, and reduced eNOS immunoreactivity in porcine PAs, while NDGA significantly inhibited this effect of RTV. Furthermore, NDGA significantly blocked RTV-induced increase of superoxide anion in the PA rings and inhibited RTV-induced decrease of glutathione in HPAECs. CONCLUSIONS: NDGA effectively inhibits the detrimental effects of HIV protease inhibitor RTV on vasomotor functions in porcine PAs. NDGA also blocks RTV-induced decrease of eNOS expression and increase of oxidative stress in both porcine PAs and HPAECs. This study may provide valuable information for the development of effective strategies for the prevention and treatment of HAART-associated cardiovascular complications. PMID- 22037734 TI - Effects of early administration of a novel anticholinergic drug on acute respiratory distress syndrome induced by sepsis. AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is the inflammatory disorder of the lung most commonly caused by sepsis. It was hypothesized that treating the lung with penehyclidine hydrochloride (PHC), a new type of hyoscyamus drug, early in the development of sepsis could diminish the lung dysfunction. MATERIAL/METHODS: Sprague-Dawley rats were divided into 4 groups: 1) a control group; 2) a sham-operated group; 3) a cecal ligation and puncture (CLP) group; 4) a PHC-treated group. One hour after CLP surgery, rats were either untreated or treated with PHC via intraperitoneal injection. Lung wet/dry weight ratio, bronchoalveolar lavage fluid (BALF), serum tumor necrosis factor (TNF alpha), interleukin 6 (IL-6), interleukin 10 (IL-10), total nitrite/nitrate (NOx), superoxide dismutase (SOD), malondialdehyde (MDA) in lung tissues, and pulmonary functions were examined 24 hour after surgery. Another 60 rats were randomly assigned to 4 equal groups to observe survival status 96 hours after surgery. RESULTS: Treatment of PHC markedly decreased TNF-alpha, IL-6, NOx, SOD, MDA content, protein concentration in BALF, and lung wet/dry weight ratio and enhanced SOD activity (p<0.05), which are indicative of PHC-induced suppression in the pathogenesis of ARDS caused by sepsis. In comparison to group CLP/saline, plasma IL-10 level markedly increased in group CLP/PHC. In PHC-treated groups, the administered PHC had a significant protective effect on the lung dysfunction induced by sepsis. CONCLUSIONS: We conclude that administration of PHC at the time of a systemic insult can protect the lung from the damaging effects of sepsis. PMID- 22037735 TI - Proanthocyanidin prevents myocardial ischemic injury in adult rats. AB - BACKGROUND: Proanthocyanidin is a bioflavonoid known to have protective effect against oxidative injury. We investigated the cardioprotective effect of proanthocyanidin. MATERIAL/METHODS: Thirty-two Rattus Norvegicus rats were categorized equally as the control group (CG), proanthocyanidin group (PCG), ischemia group (IG) and proanthocyanidin-treated group (PCT). Rats in CG and IG were fed standard rat food and PCG and PCT were fed standard rat food plus proanthocyanidin (100 mg/kg/day twice a day by oral gavage) for 3 weeks. In CG and PCG the myocardial samples were prepared immediately, and in IG and PCT hearts were placed in transport solution and kept at 4 degrees C for 5 hours, then prepared for evaluation. Malondialdehyde (MDA) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured. RESULTS: MDA levels were significantly higher in IG and PCT than in CG and PCG. The activity of SOD was significantly lower in IG and higher in PCG than in the other groups. The activity of GPx was significantly lower in IG than in the other groups. The activities of CAT were significantly lower in IG and PCT than in the other groups and were significantly lower in IG than PCT. Histopathologic evaluation revealed normal findings in CG and PCG. While ischemic injury was observed in IG, the content of muscle fibers was better preserved in PCT. CONCLUSIONS: Proanthocyanidin may have a protective effect on myocardial ischemic injury. PMID- 22037736 TI - Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor. AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that affects skeletal muscles and cardiac muscle tissue. In some cases, myocardial injury secondary to hypoxia can lead to dilative cardiomyopathy (DCM). A genetic defect in the dystrophin gene may increase the susceptibility of myocardium to hypoxia. Available data suggest that this may be caused by impaired secretion of NO, which is bound with secretion of VEGF-A. MATERIAL/METHODS: Male mice C57BI/10ScSn mdx (animal model of DMD) and healthy mice C57BI/10ScSn were exposed to hypobaric hypoxia in low-pressure chambers. Their hearts were harvested immediately after and 1, 3, 7, and 21 days after exposure to hypoxia. Normobaric mice were used as controls. The expression of VEGF-A in myocardium and cardiac vessel walls was evaluated using immunohistochemistry, Western blotting, and in situ hybridization. RESULTS: VEGF-A expression in myocardium and vessel walls of healthy mice peaked 24 hours after exposure to hypoxia. The expression of VEGF-A in vessel walls was similar in dystrophic and healthy mice; however, VEGF-A expression in the myocardium of dystrophic mice was impaired, peaking around day 7. In the heart, the total level of VEGF depends on VEGF expression in myocardium, not in vessel endothelium, and our research demonstrates that the expression of VEGF is dystrophin-dependent. CONCLUSIONS: Disordered secretion of VEGF-A in hypoxic myocardium caused the total level of this factor to be impaired in the heart. This factor, which in normal situations protect against hypoxia, promotes the gradual progression of cardiomyopathy. PMID- 22037737 TI - Activity of ozonated water and ozone against Staphylococcus aureus and Pseudomonas aeruginosa biofilms. AB - BACKGROUND: The known bactericidal properties of ozone have not been checked in relation to its action on bacterial biofilms. This is especially true of ozonated fluids. The aim of this study was to investigate the bactericidal activity of ozonated water and that of a mixture of ozone and oxygen against biofilms. MATERIAL/METHODS: Eighteen clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa exhibiting various levels of antibiotic sensitivity were investigated. Bacteria were cultured in biofilm form on polystyrene titration plates for periods of 2 to 72 hours. The biofilms formed in this way were exposed to in statu nascendi ozonated water produced in a prototype device that had been tested in clinical conditions, or to a mixture of oxygen and ozone generated in the same device. Live cells in the biofilm were stained with a 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide solution. The degree of reduction of viable bacteria following ozone exposure was determined. RESULTS: Ozonated water was found to be an effective bactericidal agent against biofilms after as little as 30 seconds of exposure, while the bactericidal activity of the ozone-oxygen solution was much lower. Prolongation of the duration of biofilm exposure to the gaseous disinfectant to 40 minutes led to a reduction in the viable cell count, which nevertheless remained high. CONCLUSIONS: Unlike the ozone-oxygen mixture, ozonated water effectively destroys bacterial biofilms in vitro.
PMID- 22037738 TI - Postcardiac injury syndrome. AB - A 58-year-old man had undergone 2-vessel off-pump coronary artery bypass surgery (OPCAB), 1 month before he was admitted into the hospital with cardiac tamponade due to pericarditis. Postcardiac injury syndrome (PCIS) was diagnosed. In spite of receiving anti-inflammatory treatment, the patient developed relapsing PCIS. PMID- 22037739 TI - Latent cytomegalovirus infection is an independent risk factor for late graft failure in renal transplant recipients. AB - BACKGROUND: Cytomegalovirus (CMV) is a risk factor for rejection and mortality soon after renal transplantation. Little is known about its consequences longer after transplantation. We prospectively investigated whether latent CMV infection is a risk factor for graft failure and mortality long after transplantation. MATERIAL/METHODS: Our study included 606 renal transplant recipients (RTR) with a functioning graft for >1 year. CMV serology was determined using ELISA. RTRs were divided into CMV-seronegative and latent CMV (seropositive + seroconverted). RESULTS: We measured CMV IgG at 6.0 [2.6-11.4] years post-transplant. During follow-up (7.0 [6.2-7.5] years), 54 (9%) RTRs experienced graft failure and 137 (23%) RTRs died. Risk for graft failure and mortality was significantly higher in RTRs with latent CMV compared to CMV-seronegative RTRs (HR=3.1, P=0.005 and HR=2.0, P=0.002, respectively). After adjustment for potential confounders, latent CMV infection remained an independent risk factor for graft failure (HR=4.6, P=0.001), but not for mortality (HR=1.4, P=0.2). CONCLUSIONS: Latent CMV is an independent risk factor for graft failure long after renal transplantation and carries a higher risk for graft failure than for mortality. These findings confirm the notion that latent CMV can be harmful in transplanted kidneys. PMID- 22037740 TI - Determination of CA-125 levels in the serum, cervical and vaginal secretions, and endometrium in Chinese women with precancerous disease or endometrial cancer. AB - BACKGROUND: Serum CA-125 has been used as a biomarker of gynecological tumors. In this study, we investigated the CA-125 levels in cervical and vaginal secretions from Chinese patients with endometrial polyps, hyperplasia and carcinoma in comparison with those in endometrium and serum. MATERIAL/METHODS: An electro chemiluminescent immunoassay was utilized to determine the levels of CA-125 in 51 healthy Chinese women and 97 patients with polyps, hyperplasia or endometrial cancer. An immunohistochemistry method was used to detect endometrial CA-125 expression in 242 subjects. RESULTS: Our study demonstrated that serum CA-125 levels were much lower than those in cervical and vaginal secretions in healthy and diseased women. The levels of CA-125 in serum, and cervical and vaginal secretions were significantly increased in complex hyperplasia and endometrial cancer. The increase of CA-125 content in serum, cervical and vaginal secretions was lesser significant in grade 3 cancer than that in grade 1 and 2 cancer. Generally, serum CA-125 levels correlated with those in cervical and vaginal secretions and CA-125 content in cervical secretion correlated with that in vaginal secretion. There was only a weak CA-125 expression in normal endometrium and simple endometrial hyperplasia. There was a significant difference in CA-125 expression among patients with pathological grade 1, 2 and 3 of endometrial carcinoma. CONCLUSIONS: Endo.metrial CA-125 expression together with its levels in the serum and cervical and vaginal secretions can be used as a potential biomarker in the diagnosis of precancerous diseases and endometrial carcinoma. PMID- 22037741 TI - Value of C-telopeptide-cross-linked Type I collagen, osteocalcin, bone-specific alkaline phosphatase and procollagen Type I N-terminal propeptide in the diagnosis and prognosis of bone metastasis in patients with malignant tumors. AB - BACKGROUND: Studies show markers of bone turnover can help the clinician in the diagnosis and follow-up of bone metastases. The present study aimed to investigate the value of biochemical markers of bone turnover in the diagnosis and prognosis of bone metastases of malignant tumors. MATERIAL/METHODS: The serum levels of C-Telopeptide-Cross-Linked Type I Collagen (CTx), Procollagen Type I N Terminal Propeptide (PINP), Bone-Specific Alkaline Phosphatase (B-ALP) and Osteocalcin (OST) in patients with bone metastases and control subjects were measured using radioimmunoassay and immunochemiluminescent assay. RESULTS: The levels of CTx, PINP, B-ALP and OST in the metastasis group were significantly higher than those in both control groups and correlated with the number of bone metastatic sites. The levels of these markers were higher in prostate cancer patients with bone metastasis. The CTX of >426 ng/ml had the highest sensitivity and NPV, and PINP of >51.21 ng/ml had the highest specificity and PPV in healthy subjects. In addition, CTX of >547 ng/ml had the highest sensitivity and OST of >20.34 ng/ml the highest specificity in the non-metastasis group. Furthermore, both B-ALP of >15.55 ng/ml had relatively high negative predictive value and positive predictive value. CONCLUSIONS: Biochemical markers of bone turnover, including CTx, PINP, B-ALP and OST, play important roles in the diagnosis and prognosis of metastatic bone cancer. CTX had a high sensitivity, and PINP had a high specificity in predicting bone metastasis. B-ALP is an ideal biochemical marker of bone turnover for metastatic bone cancer. PMID- 22037742 TI - Post-prandial endothelial dysfunction is ameliorated following weight loss in obese premenopausal women. AB - BACKGROUND: Endothelial dysfunction and postprandial hyperglycemia represent independent risk factors for cardiovascular diseases. Obesity is connected with endothelial impairments; however, it is unclear whether weight loss can modify endothelial function during the postprandial period. The aim of this study was to evaluate endothelial response (post-ischemic forearm blood flow, PIFBF) in a fasted state and following ingestion of 75 g glucose before and after very low caloric diet (VLCD). MATERIAL/METHODS: 40 obese premenopausal women (age 39.6 +/- 7.8 years, BMI 34.3 +/- 3.2 kg/m2) participated in 4-week very low caloric diet (VLCD, 800 kcal/day). Before and after VLCD, the baseline blood flow and PIFBF were measured using a mercury strain gauge plethysmography in fasting state as well as 1 hour after ingestion of 75 g glucose. RESULTS: Dietary intervention resulted in a 7% weight loss (p<0.05) and a decrease in insulin resistance index HOMA-IR (2.44 +/- 1.25 vs. 1.66 +/- 0.81, p<0.05). Before VLCD intervention, PIFBF following oral glucose challenge decreased by 8.2 +/- 9.1 ml/min/100 g tissue, while after weight loss identical stimulus increased PIFBF by 4.2 +/- 8.9 ml/min/100 g tissue (p<0.05). Plasma ICAM-1 and VCAM-1 decreased by 8% and 10%, respectively, throughout the study. CONCLUSIONS: Postprandial endothelial dysfunction is ameliorated following weight loss in obese women. This finding demonstrates the beneficial effects of weight reduction on atherosclerosis risk. PMID- 22037743 TI - Adult tibial shaft fractures - different patterns, various treatments and complications. AB - BACKGROUND: Tibial Fractures constitute a large number of emergency operations in most trauma centers. There are different approaches for tibial fractures. To our knowledge, there is insufficient evidence to consider post-operative complications in relation to both surgical methods and the types of fractures. Our purpose is to report our experience regarding the efficacy and complications associated with diverse surgical methods of different patterns of tibial shaft fractures in adults. MATERIAL/METHODS: We studied 387 adult patients. The patients' information was registered from the charts and after examination. The methods used were intramedullary interlocking nails, simple intramedullary rods, plating and external fixation. Early and late complications were recorded and by applying the DELPHI method different treatments were compared. Finally, the safest mode of treatment is proposed. RESULTS: In the intramedullary interlocking nails method the most noticeable complication was delayed union and the highest rate of complications was seen in open oblique fractures. In the simple intramedullary rods method the most frequent complication was pain, and in the with butterfly fractures the complications were the most. In the plating method the most frequent complication was pain, and most of the complications were seen in open comminuted fractures. Finally, in the external fixation method the most frequent complication was non-union and complications were the highest in the patients with oblique, comminuted and segmented fractures. CONCLUSIONS: The proposed method to treat transverse, oblique and butterfly fractures is simple intramedullary rods; whereas intramedullary interlocking nails is the better method for comminuted, segmented and spiral fractures. PMID- 22037744 TI - The importance of the presence of aggregatibacter actinomycetemcomitans in sulcus gingivalis of patients with cardiovascular diseases. AB - BACKGROUND: Over-replication of periodontal pathogens in the periodontium induces production of proinflammatory cytokines and C-reactive protein that can stimulate systemic inflammatory status and can initiate atherosclerosis and its consequences. In our pilot study we examined whether periodontal status and serum levels of interleukin-6 and C-reactive protein are associated with the presence of Aggregatibacter actinomycetemcomitans in the periodontium of patients with cardiovascular diseases (CVD). MATERIAL/METHODS: We randomly selected 38 of 166 outpatients with CVD, of which 21 patients had chronic ischemic heart disease (IHD) only and 17 had both IHD and essential hypertension (HT). The presence of Aggregatibacter actinomycetemcomitans (A.a.) in the periodontium evaluated by PCR was compared with the values of periodontal indices, namely probe depth (PD) and Community Periodontal Index of Treatment Need (CPITN), as well as with interleukin-6 (IL-6) and CRP serum levels. RESULTS: When comparing A.a.-positive and A.a.-negative groups of patients, no statistically significant differences were noticed as to the age and values of PD and CPITN, respectively. However, the proportion of CRP and IL-6 positive values was significantly higher (p <= 0.001) among A.a.-positive than in A.a.-negative patients. CONCLUSIONS: The presence of A.a. in patients with CVD may be associated with significantly higher serum levels of some proinflammatory markers. PMID- 22037746 TI - Usefulness of marking alkaline phosphatase and C-reactive protein in monitoring the risk of preterm delivery. AB - BACKGROUND: The purpose of this paper is to compare the effectiveness of use of alkaline phosphatase (ALP) and C-reactive protein (CRP) levels in marking and monitoring the risk of preterm delivery due to infection. MATERIAL/METHODS: The study involved 83 patients assigned to groups: Group I (n=43) consisted of patients hospitalized for symptoms of preterm delivery, and Group II (control group n=40) consisted of patients controlled or hospitalized delivering on time without complications, whose pregnancy had a physiological course. All patients had a single marking of ALP and CRP levels in serum performed. RESULTS: CRP levels were within the range 7 mg/l to 94 mg/l in the study group, and 4.83 mg/l to 90 mg/l in the control group. The level of ALP in the study group ranged from 139 u/l to 368 u/l and from 218 u/l to 321 u/l in the control group. In more than half of women (72.1%) from study group, CRP level exceeded 7 mg/l; in the control group, the CRP level exceeded 7 mg/l in 35% of cases. Significantly higher levels of CRP (above 20 mg/l) and ALP (above 300 u/l) were found in the 18 patients from the study group compared to the control group. CONCLUSIONS: Although an increase in the level of ALP in serum cannot be an absolute and sole marker of the risk of preterm delivery, it can be used in conjunction with a significantly elevated CRP level. PMID- 22037745 TI - Alteration of antioxidant defense status precedes humoral immune response abnormalities in macrosomia. AB - BACKGROUND: This study aimed to investigate whether the anomalies affecting the antioxidant and humoral immune defenses could start at birth and to check whether the decrease in antioxidant defenses may precede the immune abnormalities in macrosomic newborns. MATERIAL/METHODS: Thirty macrosomic and 30 sex-matched control newborns were recruited for a retrospective case-control study at the Maghnia Maternity Hospital of Tlemcen Department (Algeria). RESULTS: The serum IgG levels were similar in both groups. However, plasma ORAC, albumin, vitamin E, SOD, CAT and GSH-Px levels were significantly decreased in macrosomic as compared to control newborns, yet no difference was observed after adjustment for weight. Additionally, serum concentrations of complement C3, MDA and XO were significantly higher in macrosomic as compared to controls before adjustment for weight. Moreover, macrosomia was significantly associated with high levels of complement C3 (OR=8, p=0.002); whereas no association with those of IgG was observed (OR<1, p>0.05). Furthermore, macrosomia was significantly associated with low levels of ORAC (OR=4.96, p=0.027), vitamin E (OR=4.5, p=0.018), SOD (OR=6.88, p=0.020) and CAT (OR=5.67, p=0.017), and with high levels of MDA (OR=10.29, p=0.005). CONCLUSIONS: Abnormalities of the humoral defense system in excessive weight could be preceded by alterations of the anti-oxidative defense and by inflammatory response and activation of innate immunity at birth. Additionally, excessive weight could be a potential factor contributing to decreased anti-oxidative capacity and increased oxidative stress. PMID- 22037747 TI - An observational study on the epidemiological and mycological profile of Candidemia in ICU patients. AB - BACKGROUND: This study aimed to analyze the epidemiological and mycological profile of candidemia in intensive care unit (ICU) patients attending a tertiary care teaching hospital in the Himalayan region of northern India. MATERIAL/METHODS: A 15-bed medico-surgical ICU and a 5-bed pediatric ICU. Ninety one consecutively admitted ICU patients were screened for the presence of candidemia by performing blood cultures at periodic intervals. RESULTS: The recovered Candida isolates were speciated and subjected to antifungal susceptibility testing using standard procedures. Forty-one of the recruited patients (45%) were found to be candidemic, with the majority of patients being in the extremes of age (13 neonates and 15 >65 years of age). Four risk factors were found to be significantly associated with the occurrence of candidemia in our patients - a period of hospitalization exceeding 7 days (p=0.0008), previous use of antibiotics (p=0.001), presence of chronic renal failure (p=0.003), and ongoing cancer chemotherapy (p= 0.041). Ninety-six Candida isolates were recovered from the 41 culture-positive patients, with Candida albicans being the commonest isolate recovered (n=75, 78.1%), followed by Candida tropicalis (n=15, 16%), and Candida glabrata (n=6, 6.5%). Fluconazole resistance was observed among 26% of all Candida isolates and 17.3% of C. albicans isolates. CONCLUSIONS: Contrary to the majority of recent reports, species shift towards non-albicans candidemia has not been observed in our center, though the prevalence of azole resistance is alarmingly high even among the C. albicans isolates. PMID- 22037748 TI - The relationship of pathological gambling to criminality behavior in a sample of Polish male offenders. AB - BACKGROUND: Severe problem gambling is most often related to income producing offences such as larceny and embezzlement. In addition, the high rate of relapse to gambling problems and the link between gambling debts and crime have clinical, forensic and penitentiary implications. Considering the data from the literature presented here I decided to form and empirically verify a hypothesis that incarcerated men with a diagnosis of pathological gambling are characterized by psychopathic personality disorders, alcohol problems and criminality. MATERIAL/METHODS: The groups of participants encompassed 90 men 26-52 years of age, serving a criminal sentence. All participants had to fulfil the following clinical criteria: a) be interviewed by a psychiatrist and diagnosed with pathological gambling and/or antisocial personality disorders b) obtain a result in the PCL-R test; c) estimate the relationship between gambling problems and crime. Taking into consideration the abovementioned criteria three patient test groups were formed: Group 1, which included those for whom gambling had led to crime; Group 2, where gambling was a part of a criminal lifestyle, and Group 3, in which the mutual relationship between gambling and crime was unclear. RESULTS: The participants were diagnosed as pathological gamblers (DSM-IV-TR, ICD-10) and psychopaths (PCL-R). Those tested differed with regard to the intensification of the personality disturbance tested, the co-occurrence of other disturbances, particularly psychoactive addictions, the motivations for taking up gambling, and the type of criminal activity.
CONCLUSIONS: The hypothesis was confirmed that incarcerated men with a diagnosis of pathological gambling are characterized by psychopathic personality disorders, alcohol problems and criminality. PMID- 22037749 TI - Rituximab associated neutropenia: description of three cases and an insight into the underlying pathogenesis. AB - BACKGROUND: To describe Rituximab associated neutropenia (RAN), and to explore its underlying mechanism. CASE REPORT: We describe three patients with RAN. The effect of patient's plasma on colony forming unit, Granulocyte-Monocyte (CFU-GM) was measured by the addition of plasma to the culture of a healthy bone-marrow. Repeated tests were performed after recovery of white count. In the leukopenic period the patient's plasma inhibited CFU growth completely. Control plasma did not have such an effect. Addition of patient's cell supernatant to bone marrow cells did not change the number of CFU. The same effect was demonstrated in normal control. After recovery the patient's plasma did not inhibit colony formation, similar to control. CONCLUSIONS: RAN is a clinically significant side effect. It may take place during treatment or several months afterwards. Circulating antibodies in the plasma may be responsible for this unique BM toxicity. PMID- 22037750 TI - Salvage of a femoral nonunion after primary non-Hodgkin's lymphoma of bone: a case report and literature review. AB - BACKGROUND: With the advent of superb microsurgery techniques and advanced stabilization instruments, recent decades have seen great progress in treating nonunions secondary to traumatic fractures. However, those nonunions that are secondary to primary non-Hodgkin's lymphoma of bone and often related to irradiation still remain a challenging problem. The condition could be more perplexing when bone healing abilities are greatly compromised and reliable stabilization is difficult. CASE REPORT: We performed an operation using free vascularized fibular graft in combination with a locking plate on a 47-year-old female patient who had suffered from a three-year femoral nonunion after courses of radiochemotherapy for the treatment of primary non-Hodgkin's lymphoma of bone, a spontaneous femoral shaft fracture, an intramedullary nailing, and some nonoperative interventions in sequence. Primary union of the graft was obtained at 9 months without wound infection. No recurrence of lymphoma occurred in the 61 month follow-up, nor did a stress fracture or failure of fixation. Limb salvage was achieved and the range of motion of the adjacent joints was acceptable. CONCLUSIONS: Free vascularized fibular graft in combination with a locking plate can effectively enhance bone union in compromised bone and soft tissue milieu. More cases have yet to be further investigated. PMID- 22037751 TI - Clinical factors increasing radiation doses to patients undergoing long-lasting procedures: abdominal stent-graft implantation. AB - BACKGROUND: An important negative factor of EVAR is the radiation acquired during long-lasting procedures. The aim of the study was to document the radiation doses of EVAR and to discuss potential reasons for prolongation of radiological procedures. MATERIAL/METHODS: Dose-area product (DAP) (Gy cm2) and air kerma (AK) (Gy) obtained during EVAR from 92 patients were analyzed retrospectively in regards to body mass index (BMI), angulations of aneurysm neck, length of aneurysm neck and occurrence of tortuosity of iliac arteries. RESULTS: Total AK for fluoroscopy differed significantly between normal BMI (373 mGy) and BMI 25 29.9 (1125 mGy) or BMI >30 (1085 mGy). Iliac artery tortuosities >45 degrees and short aneurysm necks caused higher doses of total AK (1097 mGy and 1228 mGy, respectively) than iliac artery tortuosities <45 degrees and long aneurysm necks (605 mGy and 720 mGy, respectively). CONCLUSIONS: The main factors contributing to a high radiation dose being acquired by patients during EVAR are: BMI >25, tortuosity of iliac arteries >45 degrees and short aneurysm necks. PMID- 22037752 TI - Epidural and opioid analgesia following the Nuss procedure. AB - BACKGROUND: Parents have the right to decide on behalf of their children and deny consent to regional anaesthesia. The investigators decided to investigate quality of postoperative analgesia in adolescents undergoing epidural and opioid analgesia following the Nuss procedure. material/methods: The study subjects were 61 adolescents aged 11-18 years who underwent pectus excavatum repair with the Nuss procedure. Patients were divided into epidural (n=41) and opioid (n=20) groups, depending on their parents' consent to epidural catheter insertion. Intraoperatively, 0.5% epidural ropivacaine with fentanyl or intermittent intravenous injections of fentanyl were used. Postoperative analgesia was achieved with either epidural infusion of 0.1% ropivacaine with fentanyl, or subcutaneous morphine via an intraoperatively inserted "butterfly" cannula. Additionally, both groups received metamizol and paracetamol. Primary outcome variables were postoperative pain scores (Numeric Rating Scale and Prince Henry Hospital Pain Score). Secondary outcome variables included hemodynamic parameters, additional analgesia and side effects. RESULTS: Heart rate and blood pressure values in the postoperative period were significantly higher in the opioid group. Pain scores requiring intervention were noted almost exclusively in the opioid group. CONCLUSIONS: Denial of parental consent to epidural analgesia following the Nuss procedure results in significantly worse control of postoperative pain. Our data may be useful when discussing with parents the available anaesthetic techniques for exceptionally painful procedures. PMID- 22037753 TI - Waist circumference, ghrelin and selected adipose tissue-derived adipokines as predictors of insulin resistance in obese patients: preliminary results. AB - BACKGROUND: The aim of the study was to estimate the association between anthropometric obesity parameters, serum concentrations of ghrelin, resistin, leptin, adiponectin and homeostasis model assessment (HOMA-IR) in obese non diabetic insulin-sensitive and insulin-resistant patients. MATERIAL/METHODS: Study subjects included 37 obese (body mass index [BMI] >= 30 kg/m2) out-clinic patients aged 25 to 66 years. Insulin resistance was evaluated by HOMA-IR. Serum fasting concentrations of glucose, insulin, ghrelin, adiponectin, resistin and leptin were measured by using the ELISA method. Body weight, waist and hip circumferences were measured to calculate BMI and waist-to-hip ratio (WHR) values for all the patients. According to HOMA-IR, patients were divided into two groups: A, insulin sensitive (n=19); and B, insulin resistant (n=18). RESULTS: Patients with insulin resistance have greater mean waist circumference (WC) higher mean serum insulin level and leptin concentration, but lower concentrations of adiponectin and ghrelin. In the insulin-sensitive patient group we observed positive correlations between BMI and HOMA-IR, WC and HOMA-IR, and adiponectin and leptin, and negative correlations between ghrelin and HOMA-IR, WC and adiponectin, and WHR and adiponectin. In the insulin-resistant group, there was a positive correlation between resistin and ghrelin and a negative correlation between WHR and leptin. CONCLUSIONS: Waist circumference, adiponectin, leptin and ghrelin are associated with insulin resistance and may be predictors of this pathology. PMID- 22037754 TI - Therapeutic applications of mesenchymal stroma cells in pediatric diseases: current aspects and future perspectives. AB - Mesenchymal stem cells or stroma cells (MSCs) were recently proven to play various therapeutic roles when used in clinical trials to control various inflammatory, neoplastic and immunologic diseases in children. Clinical trials show some promising results, particularly in diseases where conventional therapy is still ineffective. However, experimental studies sometimes show conflicting results. This review aims to assess the current therapeutic role of MSCs in the control of several pediatric diseases and elaborate on their future applications by reviewing published studies. A review of published studies on this subject based on Pubmed and Medical Subject Heading databases, with search for all relevant articles focusing on results of clinical trials to evaluate the clinical applications of MSCs. The review includes documentation of positive as well as negative applications of MSCs focused on pediatric diseases. MSCs have important immunosuppressive and antifibrotic effects that need to be employed to help patients with diseases for which no conventional management has proven to be effective. They may be also be used as an adjuvant to conventional therapeutic modalities to consolidate recovery. This review sheds light on the significance of the use of MSCs for the treatment of various pediatric diseases and focuses on promising applications. Most of the reported studies agree about the favorable use of MSCs in various diseases; however, more clinical trials, involving larger numbers of patients, need to be conducted in order to refine the outcome of the therapeutic methods and establish standardized protocols. PMID- 22037755 TI - Erythropoietin update 2011. AB - Traditionally, erythropoietin (EPO) is described as a hematopoietic cytokine, regulating proliferation and differentiation and survival of the erythroid progenitors. The recent finding of new sites of EPO production and the wide spread distribution of EPO receptors (EPO-R) on endothelial cells, cardiomyocytes, renal cells as well as the central and peripheral nervous system raised the possibility that EPO may exert pleiotropic actions on several targets. Indeed studies (mainly preclinical) have documented protective, non hematopoietic, abilities of EPO in a variety of tissue. However, the data obtained from clinical studies are more skeptical about these properties. This article provides a comprehensive overview of EPO and its derivatives. PMID- 22037756 TI - Cultural, social and personal ways of experiencing love - an analysis of the perception of subjectivity. AB - This article is based on analysis of 4 couple's personal and public documents, in order to integrate personal choices, values and ideas with cultural representations and social attitudes. Moreover, being based on Italian sources from the nineteenth century, the study offers an historical insight on the Italian nation-building process and its political and social foundations. This study is based on archival and printed primary sources from: Gianna Maffei and Ercole Trotti Mosti (Museo Centrale del Risorgimento - Roma - MCRR); Augusto Pierantoni and Grazia Mancini (Museo Centrale del Risorgimento - Roma); Luigi Majno and Ersilia Bronzini (Archivio Unione Femminile Nazionale - Milano); Angiolo Orvieto and Laura Cantoni (Archivio Contemporaneo Bonsanti del Gabinetto Vieuesseux - Firenze - ACGV). This study reflects on love as a political and moral issue, by linking the personal sphere of subjectivity to the public dimension of the political community. An extensive understanding of the role played by the perception and the expression of sentiments can be considered as the central issue of this analysis. PMID- 22037757 TI - What dose of intravenous immunoglobulin should be administered in Kawasaki disease with suspected systemic capillary leak syndrome? Comment on: shock: an unusual presentation of Kawasaki disease (Eur J Pediatr. 2011 Jul; 170(7):941-3). PMID- 22037758 TI - The role of enzyme replacement therapy in severe Hunter syndrome-an expert panel consensus. AB - Intravenous enzyme replacement therapy (ERT) with idursulfase for Hunter syndrome has not been demonstrated to and is not predicted to cross the blood-brain barrier. Nearly all published experience with ERT with idursulfase has therefore been in patients without cognitive impairment (attenuated phenotype). Little formal guidance is available on the issues surrounding ERT in cognitively impaired patients with the severe phenotype. An expert panel was therefore convened to provide guidance on these issues. The clinical experience of the panel with 66 patients suggests that somatic improvements (e.g., reduction in liver volume, increased mobility, and reduction in frequency of respiratory infections) may occur in most severe patients. Cognitive benefits have not been seen. It was agreed that, in general, severe patients are candidates for at least a 6-12-month trial of ERT, excluding patients who are severely neurologically impaired, those in a vegetative state, or those who have a condition that may lead to near-term death. It is imperative that the treating physician discuss the goals of treatment, methods of assessment of response, and criteria for discontinuation of treatment with the family before ERT is initiated. CONCLUSION: The decision to initiate ERT in severe Hunter syndrome should be made by the physician and parents and must be based on realistic expectations of benefits and risks, with the understanding that ERT may be withdrawn in the absence of demonstrable benefits. PMID- 22037759 TI - Ciliary ultrastructural abnormalities in Mycoplasma pneumoniae pneumonia in 22 pediatric patients. AB - Mycoplasma pneumoniae pneumonia (MPP) is characterized by ciliary ultrastructural abnormalities that cause abnormal mucociliary function leading to refractory or persistent pneumonia. Herein, we analyzed ciliary ultrastructural defects in 22 children with MPP and determined the association of these defects with prognosis. Ciliary ultrastructural abnormalities occurred in all patients. Ciliated cells with loss of cilia occurred in 15. Cytoplasmic blebbing occurred in eight. Ambiguity of the "9 + 2" microtubule array occurred in six. Transposition or disarray of the peripheral microtubules occurred in five. Compound cilia occurred in three. Central complex defects occurred in three. Squamous metaplasia occurred in two. Compound cilia with multiple axonemes within a single outer sheath occurred in one. Multiple abnormalities occurred in 14. The recovery time in patients with multiple abnormalities was longer than that in patients with single abnormality. Patients with central complex defects required more than 1 month to recover. In conclusion, ciliated cells with loss of cilia, cytoplasmic blebbing, and ambiguity of the "9 + 2" microtubule array were the most commonly encountered abnormal findings in MPP. Multiple abnormalities, especially those associated with central complex defects, may indicate an unfavorable prognosis. PMID- 22037760 TI - A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by homozygous loss of the Survival Motor Neuron 1 (SMN1) gene. In the absence of SMN1, inefficient inclusion of exon 7 in transcripts from the nearly identical SMN2 gene results in ubiquitous SMN decrease but selective motor neuron degeneration. Here we investigated whether cell type-specific differences in the efficiency of exon 7 splicing contribute to the vulnerability of SMA motor neurons. We show that normal motor neurons express markedly lower levels of full length SMN mRNA from SMN2 than do other cells in the spinal cord. This is due to inefficient exon 7 splicing that is intrinsic to motor neurons under normal conditions. We also find that SMN depletion in mammalian cells decreases exon 7 inclusion through a negative feedback loop affecting the splicing of its own mRNA. This mechanism is active in vivo and further decreases the efficiency of exon 7 inclusion specifically in motor neurons of severe-SMA mice. Consistent with expression of lower levels of full-length SMN, we find that SMN-dependent downstream molecular defects are exacerbated in SMA motor neurons. These findings suggest a mechanism to explain the selective vulnerability of motor neurons to loss of SMN1. PMID- 22037761 TI - Two-step engulfment of apoptotic cells. AB - Apoptotic cells expose phosphatidylserine on their surface as an "eat me" signal, and macrophages respond by engulfing them. Although several molecules that specifically bind phosphatidylserine have been identified, the molecular mechanism that triggers engulfment remains elusive. Here, using a mouse pro-B cell line, Ba/F3, that grows in suspension, we reconstituted the engulfment of apoptotic cells. The parental Ba/F3 cells did not engulf apoptotic cells. Ba/F3 transformants expressing T cell immunoglobulin- and mucin-domain-containing molecule 4 (Tim4), a type I membrane protein that specifically binds phosphatidylserine, efficiently bound apoptotic cells in a phosphatidylserine dependent manner but did not engulf them. However, Ba/F3 transformants expressing both Tim4 and the integrin alpha(v)beta(3) complex bound to and engulfed apoptotic cells in the presence of milk fat globule epidermal growth factor factor VIII (MFG-E8), a secreted protein that can bind phosphatidylserine and integrin alpha(v)beta(3). These results indicate that the engulfment of apoptotic cells proceeds in two steps: Tim4 tethers apoptotic cells, and the integrin alpha(v)beta(3) complex mediates engulfment in coordination with MFG-E8. A similar two-step engulfment of apoptotic cells was observed with mouse resident peritoneal macrophages. Furthermore, the Tim4/integrin-mediated engulfment by the Ba/F3 cells was enhanced in cells expressing Rac1 and Rab5, suggesting that this system well reproduces the engulfment of apoptotic cells by macrophages. PMID- 22037762 TI - Notch signaling in Sertoli cells regulates cyclical gene expression of Hes1 but is dispensable for mouse spermatogenesis. AB - Mammalian spermatogenesis is a highly regulated system dedicated to the continuous production of spermatozoa from spermatogonial stem cells, and the process largely depends on microenvironments created by Sertoli cells, unique somatic cells that reside within a seminiferous tubule. Spermatogenesis progresses with a cyclical program known as the "seminiferous epithelial cycle," which is accompanied with cyclical gene expression changes in Sertoli cells. However, it is unclear how the cyclicity in Sertoli cells is regulated. Here, we report that Notch signaling, which is known to play an important role for germ cell development in Drosophila and Caenorhabditis elegans, is cyclically activated in Sertoli cells and regulates stage-dependent gene expression of Hes1. To elucidate the regulatory mechanism of stage-dependent Hes1 expression and the role of Notch signaling in mouse spermatogenesis, we inactivated Notch signaling in Sertoli cells by deleting protein O-fucosyltransferase 1 (Pofut1), using the cre-loxP system, and found that stage-dependent Hes1 expression was dependent on the activation of Notch signaling. Unexpectedly, however, spermatogenesis proceeded normally. Our results thus indicate that Notch signaling regulates cyclical gene expression in Sertoli cells but is dispensable for mouse spermatogenesis. This highlights the evolutionary divergences in regulation of germ cell development. PMID- 22037763 TI - Cross talk between immunoglobulin heavy-chain transcription and RNA surveillance during B cell development. AB - Immunoglobulin (Ig) genes naturally acquire frequent premature termination codons during the error-prone V(D)J recombination process. Although B cell differentiation is linked to the expression of productive Ig alleles, the transcriptional status of nonfunctionally recombined alleles remains unclear. Here, we tracked transcription and posttranscriptional regulation for both Ig heavy-chain (IgH) alleles in mice carrying a nonfunctional knock-in allele. We show that productively and nonproductively VDJ-rearranged alleles are transcribed throughout B cell development, carry similar active chromatin marks, and even display equivalent RNA polymerase II (RNAPII) loading after B cell stimulation. Hence, these results challenge the idea that the repositioning of one allele to heterochromatin could promote the silencing of nonproductive alleles. Interestingly, the efficiency of downstream RNA surveillance mechanisms fluctuates according to B cell activation and terminal differentiation: unspliced nonfunctional transcripts accumulate in primary B cells, while B cell activation promotes IgH transcription, RNA splicing, and nonsense-mediated mRNA decay (NMD). Altogether, IgH transcription and RNA splicing rates determine by which RNA surveillance mechanisms a B cell can get rid of nonproductive IgH mRNAs. PMID- 22037764 TI - Localization of HET-S to the cell periphery, not to [Het-s] aggregates, is associated with [Het-s]-HET-S toxicity. AB - Prion diseases are associated with accumulation of the amyloid form of the prion protein, but the mechanisms of toxicity are unknown. Amyloid toxicity is also associated with fungal prions. In Podospora anserina, the simultaneous presence of [Het-s] prion and its allelic protein HET-S causes cell death in a self /nonself-discrimination process. Here, using the prion form of a fragment of HET s ([PrD(157)(+)]), we show that [Het-s]-HET-S toxicity can be faithfully recapitulated in yeast. Overexpression of Hsp40 chaperone, Sis1, rescues this toxicity by curing cells of [PrD(157)(+)]. We find no evidence for toxic [PrD(157)(+)] conformers in the presence of HET-S. Instead, [PrD(157)(+)] appears to seed HET-S to accumulate at the cell periphery and to form aggregates distinct from visible [PrD(157)(+)] aggregates. Furthermore, HET-S mutants that cause HET S to be sequestered into [PrD(157)(+)] prion aggregates are not toxic. The localization of HET-S at the cell periphery and its association with cell death was also observed in the native host Podospora anserina. Thus, upon interaction with [Het-s], HET-S localizes to the cell periphery, and this relocalization, rather than the formation of mixed HET-s/HET-S aggregates, is associated with toxicity. PMID- 22037765 TI - Loss of Akt1 in mice increases energy expenditure and protects against diet induced obesity. AB - Akt is encoded by a gene family for which each isoform serves distinct but overlapping functions. Based on the phenotypes of the germ line gene disruptions, Akt1 has been associated with control of growth, whereas Akt2 has been linked to metabolic regulation. Here we show that Akt1 serves an unexpected role in the regulation of energy metabolism, as mice deficient for Akt1 exhibit protection from diet-induced obesity and its associated insulin resistance. Although skeletal muscle contributes most of the resting and exercising energy expenditure, muscle-specific deletion of Akt1 does not recapitulate the phenotype, indicating that the role of Akt1 in skeletal muscle is cell nonautonomous. These data indicate a previously unknown function of Akt1 in energy metabolism and provide a novel target for treatment of obesity. PMID- 22037766 TI - Mink1 regulates beta-catenin-independent Wnt signaling via Prickle phosphorylation. AB - beta-Catenin-independent Wnt signaling pathways have been implicated in the regulation of planar cell polarity (PCP) and convergent extension (CE) cell movements. Prickle, one of the core proteins of these pathways, is known to asymmetrically localize proximally at the adherens junction of Drosophila melanogaster wing cells and to locally accumulate within plasma membrane subdomains in cells undergoing CE movements during vertebrate development. Using mass spectrometry, we have identified the Ste20 kinase Mink1 as a Prickle associated protein and found that they genetically interact during the establishment of PCP in the Drosophila eye and CE in Xenopus laevis embryos. We show that Mink1 phosphorylates Prickle on a conserved threonine residue and regulates its Rab5-dependent endosomal trafficking, a process required for the localized plasma membrane accumulation and function of Prickle. Mink1 also was found to be important for the clustering of Vangl within plasma membrane puncta. Our results provide a link between Mink and the Vangl-Prickle complex and highlight the importance of Prickle phosphorylation and endosomal trafficking for its function during Wnt-PCP signaling. PMID- 22037767 TI - Ku regulates signaling to DNA damage response pathways through the Ku70 von Willebrand A domain. AB - The Ku heterodimer (Ku70/Ku80) is a main component of the nonhomologous end joining (NHEJ) pathway that repairs DNA double-strand breaks (DSBs). Ku binds the broken DNA end and recruits other proteins to facilitate the processing and ligation of the broken end. While Ku interacts with many proteins involved in DNA damage/repair-related functions, few interactions have been mapped to the N terminal von Willebrand A (vWA) domain, a predicted protein interaction domain. The mutagenesis of Ku70 vWA domain S155/D156 unexpectedly increased cell survival following ionizing radiation (IR) treatment. DNA repair appeared unaffected, but defects in the activation of apoptosis and alterations in the DNA damage signaling response were identified. In particular, Ku70 S155A/D156A affected the IR-induced transcriptional response of several activating transcription factor 2 (ATF2)-regulated genes involved in apoptosis regulation. ATF2 phosphorylation and recruitment to DNA damage-induced foci was increased in Ku70-deficient cells, suggesting that Ku represses ATF2 activation. Ku70 S155A/D156A substitutions further enhanced this repression. S155A substitution alone was sufficient to confer enhanced survival, whereas alteration to a phosphomimetic residue (S155D) reversed this effect, suggesting that S155 is a phosphorylation site. Thus, these findings infer that Ku links signals from the DNA repair machinery to DNA damage signaling regulators that control apoptotic pathways. PMID- 22037768 TI - The small heat shock protein ODF1/HSPB10 is essential for tight linkage of sperm head to tail and male fertility in mice. AB - Sperm motility and hence male fertility strictly depends on proper development of the sperm tail and its tight anchorage to the head. The main protein of sperm tail outer dense fibers, ODF1/HSPB10, belongs to the family of small heat shock proteins that function as molecular chaperones. However, the impact of ODF1 on sperm tail formation and motility and on male fecundity is unknown. We therefore generated mutant mice in which the Odf1 gene was disrupted. Heterozygous mutant male mice are fertile while sperm motility is reduced, but Odf1-deficient male mice are infertile due to the detachment of the sperm head. Although headless tails are somehow motile, transmission electron microscopy revealed disturbed organization of the mitochondrial sheath, as well as of the outer dense fibers. Our results thus suggest that ODF1, besides being involved in the correct arrangement of mitochondrial sheath and outer dense fibers, is essential for rigid junction of sperm head and tail. Loss of function of ODF1, therefore, might account for some of the cases of human infertility with decapitated sperm heads. In addition, since sperm motility is already affected in heterozygous mice, impairment of ODF1 might even account for some cases of reduced fertility in male patients. PMID- 22037769 TI - Identification of a Src tyrosine kinase/SIAH2 E3 ubiquitin ligase pathway that regulates C/EBPdelta expression and contributes to transformation of breast tumor cells. AB - The transcription factor CCAAT/enhancer-binding protein delta (C/EBPdelta, CEBPD) is a tumor suppressor that is downregulated during breast cancer progression but may also promote metastasis. Here, we have investigated the mechanism(s) regulating C/EBPdelta expression and its role in human breast cancer cells. We describe a novel pathway by which the tyrosine kinase Src downregulates C/EBPdelta through the SIAH2 E3 ubiquitin ligase. Src phosphorylates SIAH2 in vitro and leads to tyrosine phosphorylation and activation of SIAH2 in breast tumor cell lines. SIAH2 interacts with C/EBPdelta, but not C/EBPbeta, and promotes its polyubiquitination and proteasomal degradation. Src/SIAH2-mediated inhibition of C/EBPdelta expression supports elevated cyclin D1 levels, phosphorylation of retinoblastoma protein (Rb), motility, invasive properties, and survival of transformed cells. Pharmacological inhibition of Src family kinases by SKI-606 (bosutinib) induces C/EBPdelta expression in an SIAH2 dependent manner, which is necessary for "therapeutic" responses to SKI-606 in vitro. Ectopic expression of degradation-resistant mutants of C/EBPdelta, which do not interact with SIAH2 and/or cannot be polyubiquitinated, prevents full transformation of MCF-10A cells by activated Src (Src truncated at amino acid 531 [Src-531]) in vitro. These data reveal that C/EBPdelta expression can be regulated at the protein level by oncogenic Src kinase signals through SIAH2, thus contributing to breast epithelial cell transformation. PMID- 22037770 TI - Does change in cannabis use in established psychosis affect clinical outcome? AB - BACKGROUND: Cannabis use has been identified as a potent predictor of the earlier onset of psychosis, but meta-analysis has not indicated that it has a clear effect in established psychosis. AIM: To assess the association between cannabis and outcomes, including whether change in cannabis use affects symptoms and functioning, in a large sample of people with established nonaffective psychosis and comorbid substance misuse. METHODS: One hundred and sixty participants whose substance use included cannabis were compared with other substance users (n = 167) on baseline demographic, clinical, and substance use variables. The cannabis using subgroup was examined prospectively with repeated measures of substance use and psychopathology at baseline, 12 months, and 24 months. We used generalized estimating equation models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes. RESULTS: Cannabis users showed cross-sectional differences from other substances users but not in terms of positive symptoms. Second, cannabis dose was not associated with subsequent severity of positive symptoms and change in cannabis dose did not predict change in positive symptom severity, even when patients became abstinent. However, greater cannabis exposure was associated with worse functioning, albeit with a small effect size. CONCLUSIONS: We did not find evidence of an association between cannabis dose and psychotic symptoms, although greater cannabis dose was associated with worse psychosocial functioning, albeit with small effect size. It would seem that within this population, not everyone will demonstrate durable symptomatic improvements from reducing cannabis. PMID- 22037771 TI - Niacin: the evidence, clinical use, and future directions. AB - The use of FDA-approved niacin (nicotinic acid or vitamin B3) formulations at therapeutic doses, alone or in combination with statins or other lipid therapies, is safe, improves multiple lipid parameters, and reduces atherosclerosis progression. Niacin is unique as the most potent available lipid therapy to increase high-density lipoprotein (HDL) cholesterol and it significantly reduces lipoprotein(a). Through its action on the GPR109A receptor, niacin may also exert beneficial pleiotropic effects independent of changes in lipid levels, such as improving endothelial function and attenuating vascular inflammation. Studies evaluating the impact of niacin in statin-naive patients on cardiovascular outcomes, or alone and in combination with statins or other lipid therapies on atherosclerosis progression, have been universally favorable. However, the widespread use of niacin to treat residual lipid abnormalities such as low HDL cholesterol, when used in combination with statins among patients achieving very low (<75 mg/dL) low-density lipoprotein cholesterol levels, is currently not supported by clinical outcome trials. PMID- 22037772 TI - Lipid effects of antihypertensive medications. AB - Thiazide diuretics and beta-blockers are first-line therapies for hypertension unless there are compelling indications for other drug classes. Diuretics and beta-blockers, however, may worsen dyslipidemia and glucose tolerance whereas antihypertensive agents in other drug classes may have neutral or beneficial effects. Initial clinical trials of antihypertensive regimens suggested that blood pressure lowering was the most important aspect of therapy and that the adverse effects on lipids and glucose tolerance did not impact clinical outcomes. Newer trials, however, question this finding and implicate these pleotropic effects as contributing to the results of the trials. Patients with cardiometabolic risk factors may have compelling indications for agents that inhibit the renin-angiotensin-aldosterone system, relegating diuretics and beta blockers to third-line therapy. PMID- 22037773 TI - A comparative study of two different methods of sample preparation for positive blood cultures for the rapid identification of bacteria using MALDI-TOF MS. AB - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has lately been implemented as a solid technology for rapid microorganism identification in microbiology laboratories. This study compares two methods for bacterial separation from 85 positive blood culture before MALDI TOF MS: (1) a conventional method that we used in our laboratory to prepare bacteria for susceptibility testing and (2) a new commercialized technique (Sepsityper). There were no significant differences in the identification of Gram negative bacilli regardless of the bacterial separation method used. However, identification was greater for Gram-positive cocci when the Sepsityper method was used (84.15% vs. 100% in the identification to a genus level in staphylococci and 57.14% vs. 85.71% in the identification to a genus level of enterococci with the in-house and Sepsityper methods, respectively). Therefore, the Sepsityper method to prepare bacteria from a positive blood culture is more adequate for the further identification of Gram-positive cocci by MALDI-TOF MS. PMID- 22037774 TI - Performance of the GenoType(r) MTBDRPlus assay in routine settings: a multicenter study. AB - Former Soviet Union countries including the Baltic States (Latvia, Lithuania, and Estonia) are hot spots for an emerging epidemic of drug resistant tuberculosis (TB). As a part of the development of a co-ordinated network of centers for diagnostic trials across Eastern Europe we conducted a retrospective multicenter analysis of the performance of the GenoType(r) MTBDRPlus assay for TB identification and susceptibility to isoniazid (INH) and rifampicin (RIF) in routine settings. A total of 1,045 primary samples, 1045 TB cultures derived from these specimens and 306 separate M. tuberculosis isolates tested in 2007-2010 at four participating sites (Tartu, Estonia; Riga, Latvia; Vilnius, Lithuania; and Samara, Russian Federation) were included in the analysis. The pooled sensitivity and specificity values for RIF and INH were 95.3% and 95.5%, 89.9 and 87.1%, respectively; there were no statistically significant variations in performance across sites. The proportion of multidrug resistant (MDR) strains in the collections ranged from 21.8% (in Estonia) to 55.9% (in Russia). In a routine non trial context, the assay reliably detected both rifampicin and isoniazid resistance. The absence of statistically significant differences between sites suggested that the comparable performance obtained using these assays has helped demonstrate the formation of a successful diagnostic trial network. PMID- 22037775 TI - A survey on the use of gentamicin in infective endocarditis. AB - US and European guidelines recommend a daily divided gentamicin dose (3 mg/kg in two or three equally divided doses) for the treatment of infective endocarditis caused by staphylococci or enterococci, but once-daily dosing (3 mg/kg/day) is recommended for streptococcal endocarditis. However, studies have recommended the use of higher doses of gentamicin (4 or >=5 mg/kg/day) administered once-daily. A survey was conducted in France by mailing a questionnaire to the 595 members of the French Infectious Disease Society regarding their gentamicin prescription patterns in infective endocarditis, focusing on the dosing regimen. The survey was answered by 137 physicians (23%). The proportions of physicians following guideline-based regimens were similar for each organism (30.9%, 38.8%, and 39.4% for staphylococci, enterococci, and streptococci, respectively [p=0.26]). In contrast, the proportions of physicians following literature-based regimens were significantly different for each organism (59.6%, 42.5%, and 27.7% for staphylococci, enterococci, and streptococci, respectively [p<0.001]). The number of years practicing and the type of practice (university vs. non-university hospital) did not influence the gentamicin dose or regimen. Although adherence to published guidelines for gentamicin administration in patients with infective endocarditis was poor, a large proportion of physicians who did not follow those guidelines used literature-based regimens. PMID- 22037776 TI - The metal-carbonyl...pi(aryl) interaction as a supramolecular synthon for the stabilisation of transition metal carbonyl crystal structures. AB - M-carbonyl(lone pair)...pi(aryl) interactions provide stability to their transition metal crystal structures. This supramolecular synthon usually leads to zero- or one-dimensional aggregation patterns; a rare example of a three dimensional architecture based on the M-CO(lone pair)...pi(aryl) synthon has also been revealed. PMID- 22037777 TI - Dorsal iliac dimensions in elderly females: anatomical considerations in two bolt iliac foundation construct. AB - PURPOSE: To detect the presence of differences in transverse dimensions in the female iliac blades in comparison to normal population groups. METHODS: The present study measures the transverse dimensions of female iliac blades from cadavers and dried bone specimens from women in the age group 50-70 years and compares with similar measurements taken from adult male dried hip bones. Five transverse dimensions were recorded in each iliac bone at equidistant positions twice. Once, the dimensions were measured along the upper segment and then along the lower segment of the bone. Both segments corresponded approximately to the directions of placement of screws in the two bolt iliac foundation. Hemi-pelvises from cadavers were sectioned vertically at equidistant planes and the sections were directly measured for the thickness at the cut surfaces in the two segments along the probable route of screw placement. RESULTS: The lower segments were thicker and bulkier along the greater part of their length than the upper ones. The differences of dimensions between the two sides from the same individual and between the two groups were negligible and statistically insignificant. Thickness at the dorsal aspect of the hip-bone (ilium) in elderly females was comparable to male ones. CONCLUSION: Measurements along the path of screw placements for a two bolt pelvic foundation in elderly females were found to be comparable with dimensions observed in the other samples used in the study. PMID- 22037778 TI - Anatomical bases of endoscopic tarsal tunnel release: anatomical and ultra sonographic study with a preliminary clinical report. AB - PURPOSE: The purpose of our study is to present the anatomical bases of a new technique for endoscopic tarsal release and to report the preliminary clinical outcome for this technique. METHOD: Anatomical study The technique was performed on 12 intact adult lower limb specimens. The location of portals was evaluated as well as the integrity of the neurovascular bundle. Ultra-sonographic study A prospective case control study was done on 10 patients (11 feet) and 14 normal volunteers (28 feet). Three parameters were measured; the thickness of flexor retinaculum, the nerve cross-section area and the depth of tarsal tunnel. Clinical study Seven patients with idiopathic proximal Tarsal Tunnel Syndrome (TTS) were treated by endoscopic TTR using a modified trocar cannula and dilator system. Preoperative and postoperative evaluation was done by electrophysiological studies and ultra-sonography. Evaluation was done using Takakura's rating scale. RESULTS: Anatomical study The proximal and distal portals were located at 13 mm (+/-1.59 STD) and 17.91 mm (+/-1.44 STD) from the proximal and distal borders of FR, respectively. There was intact neurovascular bundle in all specimens. Ultra-sonographic study There was statistically significant difference in the mean nerve cross-sectional area and the thickness of the FR between the control group and the patients group (P < 0.05). Clinical study The mean TRS improved from 2.28 +/- 1.11 STD preoperatively to 8.43 +/- 0.97 at 2 years follow-up. The overall good to excellent results was 85.7%. CONCLUSION: Based on this preliminary clinical study, endoscopic tarsal tunnel release by the technique described could obtain excellent to good results in 85.7% of patients with idiopathic proximal tarsal tunnel. The anatomical study proved the safety of the technique on the neurovascular structures. Ultra sonography was an effective tool for preoperative diagnosis and postoperative follow-up. LEVEL OF EVIDENCE: Case series study, Level IV. PMID- 22037780 TI - A systematic review of breast cancer incidence risk prediction models with meta analysis of their performance. AB - A risk prediction model is a statistical tool for estimating the probability that a currently healthy individual with specific risk factors will develop a condition in the future such as breast cancer. Reliably accurate prediction models can inform future disease burdens, health policies and individual decisions. Breast cancer prediction models containing modifiable risk factors, such as alcohol consumption, BMI or weight, condom use, exogenous hormone use and physical activity, are of particular interest to women who might be considering how to reduce their risk of breast cancer and clinicians developing health policies to reduce population incidence rates. We performed a systematic review to identify and evaluate the performance of prediction models for breast cancer that contain modifiable factors. A protocol was developed and a sensitive search in databases including MEDLINE and EMBASE was conducted in June 2010. Extensive use was made of reference lists. Included were any articles proposing or validating a breast cancer prediction model in a general female population, with no language restrictions. Duplicate data extraction and quality assessment were conducted. Results were summarised qualitatively, and where possible meta analysis of model performance statistics was undertaken. The systematic review found 17 breast cancer models, each containing a different but often overlapping set of modifiable and other risk factors, combined with an estimated baseline risk that was also often different. Quality of reporting was generally poor, with characteristics of included participants and fitted model results often missing. Only four models received independent validation in external data, most notably the 'Gail 2' model with 12 validations. None of the models demonstrated consistently outstanding ability to accurately discriminate between those who did and those who did not develop breast cancer. For example, random-effects meta analyses of the performance of the 'Gail 2' model showed the average C statistic was 0.63 (95% CI 0.59-0.67), and the expected/observed ratio of events varied considerably across studies (95% prediction interval for E/O ratio when the model was applied in practice was 0.75-1.19). There is a need for models with better predictive performance but, given the large amount of work already conducted, further improvement of existing models based on conventional risk factors is perhaps unlikely. Research to identify new risk factors with large additionally predictive ability is therefore needed, alongside clearer reporting and continual validation of new models as they develop. PMID- 22037779 TI - Life stage differences in mammary gland gene expression profile in non-human primates. AB - Breast cancer (BC) is the most common malignancy of women in the developed world. To better understand its pathogenesis, knowledge of normal breast development is crucial, as BC is the result of disregulation of physiologic processes. The aim of this study was to investigate the impact of reproductive life stages on the transcriptional profile of the mammary gland in a primate model. Comparative transcriptomic analyses were carried out using breast tissues from 28 female cynomolgus macaques (Macaca fascicularis) at the following life stages: prepubertal (n = 5), adolescent (n = 4), adult luteal (n = 5), pregnant (n = 6), lactating (n = 3), and postmenopausal (n = 5). Mammary gland RNA was hybridized to Affymetrix GeneChip((r)) Rhesus Macaque Genome Arrays. Differential gene expression was analyzed using ANOVA and cluster analysis. Hierarchical cluster analysis revealed distinct separation of life stage groups. More than 2,225 differentially expressed mRNAs were identified. Gene families or pathways that changed across life stages included those related to estrogen and androgen (ESR1, PGR, TFF1, GREB1, AR, 17HSDB2, 17HSDB7, STS, HSD11B1, AKR1C4), prolactin (PRLR, ELF5, STAT5, CSN1S1), insulin-like growth factor signaling (IGF1, IGFBP1, IGFBP5), extracellular matrix (POSTN, TGFB1, COL5A2, COL12A1, FOXC1, LAMC1, PDGFRA, TGFB2), and differentiation (CD24, CD29, CD44, CD61, ALDH1, BRCA1, FOXA1, POSTN, DICER1, LIG4, KLF4, NOTCH2, RIF1, BMPR1A, TGFB2). Pregnancy and lactation displayed distinct patterns of gene expression. ESR1 and IGF1 were significantly higher in the adolescent compared to the adult animals, whereas differentiation pathways were overrepresented in adult animals and pregnancy-associated life stages. Few individual genes were distinctly different in postmenopausal animals. Our data demonstrate characteristic patterns of gene expression during breast development. Several of the pathways activated during pubertal development have been implicated in cancer development and metastasis, supporting the idea that other developmental markers may have application as biomarkers for BC. PMID- 22037781 TI - Lipidomic approach to identify patterns in phospholipid profiles and define class differences in mammary epithelial and breast cancer cells. AB - Breast cancer is the leading cause of cancer-related deaths in women. Altered cellular functions of cancer cells lead to uncontrolled cellular growth and morphological changes. Cellular biomembranes are intimately involved in the regulation of cell signaling; however, they remain largely understudied. Phospholipids (PLs) are the main constituents of biological membranes and play important functional, structural and metabolic roles. The aim of this study was to establish if patterns in the PL profiles of mammary epithelial cells and breast cancer cells differ in relation to degree of differentiation and metastatic potential. For this purpose, PLs were analyzed using a lipidomic approach. In brief, PLs were extracted using Bligh and Dyer method, followed by a separation of PL classes by thin layer chromatography, and subsequent analysis by mass spectrometry (MS). Differences and similarities were found in the relative levels of PL content between mammary epithelial and breast cancer cells and between breast cancer cells with different levels of aggressiveness. When compared to the total PL content, phosphatidylcholine levels were reduced and lysophosphatydilcholines increased in the more aggressive cancer cells; while phosphatidylserine levels remained unchanged. MS analysis showed alterations in the classes of phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, and phosphatidylinositides. In particular, the phosphatidylinositides, which are signaling molecules that affect proliferation, survival, and migration, showed dramatic alterations in their profile, where an increase of phosphatdylinositides saturated fatty acids chains and a decrease in C20 fatty acids in cancer cells compared with mammary epithelial cells was observed. At present, information about PL changes in cancer progression is lacking. Therefore, these data will be useful as a starting point to define possible PLs with prospective as biomarkers and disclose metabolic pathways with potential for therapy. PMID- 22037782 TI - Resolution of extensive leptomeningeal metastasis and clinical spinal cord compression from breast cancer using weekly docetaxel chemotherapy. AB - Metastatic breast cancer to the leptomeninges is a late event in the disease course and is associated with significant morbidity and a grave prognosis. Treatment typically involves direct intrathecal injection of chemotherapy into the cerebrospinal fluid compartment since systemic chemotherapy penetrates poorly to the central nervous system. Here we report an interesting clinical observation involving a patient presenting with leptomeningeal spread of breast cancer causing extensive spinal cord compression with obliteration of the subarachnoid space, thus precluding the use of direct intrathecal chemotherapy. We administered systemic chemotherapy using weekly docetaxel with complete radiographic resolution of her disease and recovery from clinical spinal cord compression. While this is a single clinical observation, weekly administration of docetaxel in this circumstance may have been associated with improved drug "escape" into the central nervous system and better antitumor effect. Because leptomeningeal disease is typically a late event in metastatic breast cancer, resistance to therapeutic intervention may reflect intrinsically resistant disease in the setting of extensive prior therapy rather than a routine problem with systemic drug delivery to the CNS. Studying patterns of disease relapse in patients who had received adjuvant weekly taxanes may provide insights into this hypothesis. PMID- 22037783 TI - Prognostic impact of polymorphisms in the MYBL2 interacting genes in breast cancer. AB - MYBL2 is a transcription factor, which regulates the expression of genes involved in cancer progression. In this study, we investigated whether putative functional variants in genes regulating MYBL2 (E2F1, E2F3 and E2F4) or in genes, which are regulated by MYBL2 (BCL2, BIRC5, COL1A1, COL1A2, COL5A2, ERBB2, CLU, LIN9 and TOP2A) affect breast cancer (BC) susceptibility and clinical outcome. Twenty eight SNPs were genotyped in a population-based series of 782 Swedish BC cases and 1,559 matched controls. BC-specific survival analysis of BIRC5 suggested that carriers of the minor allele of rs8073069 and rs1042489 have a worse survival compared with the major homozygotes (HR 2.46, 95% CI 1.39-4.36 and HR 1.81, 95% CI 1.01-3.25, respectively). The poor survival was observed especially in women with aggressive tumours. Multivariate analysis supported the role of rs8073069 as an independent prognostic marker. For BCL2, minor allele carriers of rs1564483 were more likely to have hormone receptor-positive tumours than the major homozygotes. Another SNP in BCL2, rs4987852, was associated with tumour stages II IV and histologic grade 3. In CLU, the minor allele carriers of rs9331888 were more likely to have tumours with regional lymph node metastasis and stages II-IV than the major homozygotes. In conclusion, our study suggests a role of genetic variation in BIRC5, BCL2 and CLU as progression and prognostic markers for BC, supporting previous studies based on the expression of the genes. PMID- 22037784 TI - The postmenopausal hormone replacement therapy-related breast cancer risk is decreased in women carrying the CYP2C19*17 variant. PMID- 22037785 TI - Clinician awareness and knowledge of breast cancer-related lymphedema in a large, integrated health care delivery setting. AB - Breast cancer survivors have reported dissatisfaction regarding their education on risk of breast cancer-related lymphedema (BCRL) from clinicians. We describe clinician knowledge and treatment referral of patients with BCRL among active oncologists, surgeons, and primary care physicians in the Kaiser Permanente Northern California Medical Care Program. A total of 887 oncologists, surgeons, and primary care clinicians completed a 10-minute web survey from May 2, 2010 to December 31, 2010 on BCRL knowledge, education, and referral patterns. A knowledge score of BCRL was calculated based on clinician responses. Multivariable regression models were used to determine the associations of selected covariates with BCRL knowledge score and clinician referral, respectively. Compared with primary care clinicians, oncologists had the highest mean score followed closely by surgeons (P < 0.0001). In multivariable analyses, being female, an oncologist or surgeon, and recently receiving BCRL materials were each significantly associated with higher BCRL knowledge scores. About 44% of clinicians (n = 381) indicated they had ever made a BCRL referral (100% oncologists, 79% surgeons, and 36% primary care clinicians). Clinicians with a higher knowledge score were more likely to make referrals. In stratified analyses by specialty, the significant associated factors remained for primary care but became non-significant for oncology and surgery. These results can inform educational interventions to strengthen clinician knowledge of the clinical management of BCRL, especially among primary care clinicians. With the growing number of breast cancer survivors, increasing clinician education about BCRL across all specialties is warranted. PMID- 22037786 TI - Regarding "Co-expression of SNAIL and TWIST determines prognosis in estrogen receptor-positive early breast cancer patients". PMID- 22037787 TI - Predictive value of neoadjuvant chemotherapy failure in breast cancer using FDG PET after the first course. AB - The aim of this study was to prospectively evaluate the predictive value of (18)F fluorodeoxyglucose-positron emission tomography (FDG-PET) to detect the absence of pathological response to preoperative chemotherapy in patients (pts) with breast cancer. 63 consecutive pts with non-metastatic, non-inflammatory breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 Docetaxel) were enrolled. FDG-PET was performed just before the first as well as before the second course. Metabolic activity (tumour FDG uptake) was measured by standardised uptake value (SUV(max)). Pts were classified as non-responders (NR) when the decrease of SUV(max) in the primary tumour was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG-PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after three cycles, pathological complete response (pCR) after surgery (according to Sataloff classification) and 4-year relapse-free survival (RFS). The mean SUV(max) decrease according to histological response was -52 +/- 21% in case of pCR (Sataloff A) and 25 +/- 34% in other cases (Sataloff B + C + D). Out of the 16 pts with no PET response (SUV decrease less than 15%), only one had a clinical response after the third cycle, and no pCR was observed. The 4-year RFS rate was significantly longer for metabolic responders than for NR (respectively, 85 vs. 44%; P = 0.01). This prospective study shows that a decrease in the SUV of less than 15% after the first chemotherapy course is a very potent predictor for failure of neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this was shown despite the fact that the chemotherapy regimen was changed after the third course. PMID- 22037788 TI - Folate intake and breast cancer mortality in a cohort of Swedish women. AB - Folate may influence breast cancer development and progression through its role in one-carbon metabolism. However, epidemiologic data on the relation between folate and breast cancer survival are limited. We investigated whether dietary folate intake was associated with survival in 3,116 women diagnosed with breast cancer in the population-based Swedish Mammography Cohort. Participants completed a 67-item food frequency questionnaire in 1987. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for death from breast cancer and death from any cause. During 25,716 person-years of follow-up from 1987 to 2008, there were 852 deaths with 381 breast cancer deaths. Dietary folate intake was inversely associated with breast cancer and overall mortality. Women in the highest quartile of folate intake had a multivariable HR (95% CI) of death from breast cancer of 0.78 (0.58-1.03) compared to those in the lowest quartile (P (trend) = 0.03). The corresponding HR (95% CI) for death from any cause was 0.79 (0.66-0.96; P (trend) = 0.004). The protective association between dietary folate intake and breast cancer death was strongest among those with ER-negative tumors (HR = 0.42; 95% = CI 0.22-0.79; P (trend) = 0.01) comparing the highest to lowest quartile. Our findings suggest that folate intake before breast cancer diagnosis may improve breast cancer and overall survival. While these findings need to be confirmed in future studies, they do offer assurance that dietary folate intake at the levels observed in our population does not unfavorably affect survival after breast cancer. PMID- 22037789 TI - Cycling of rare earth elements in the atmosphere in central Tokyo. AB - Concentrations of 14 rare earth elements (REEs) in six size classes of airborne particulate matter (APM) (<0.43, 0.43-0.65, 0.65-1.1, 1.1-2.1, 2.1-11, and >11 MUm) and in two different phases (suspended particulate and dissolved) in rainwater were determined by inductively coupled plasma mass spectrometry (ICP MS). Positive Eu and Tb anomalies were observed in size-classified APM. These anomalies may be due to large emissions of Eu and Tb to the atmosphere resulting from the recent change in Japan from the use of cathode-ray tubes to plasma displays in television sets (Eu and Tb) and from the widespread use of magneto optical disks (Tb). The light REEs were enriched in fine APM particles (diameter < 1.1 MUm). Because compositions of La/Ce/Sm in fine APM (diameter < 1.1 MUm) were similar to those in automobile catalyst, the light REE enrichment was attributed to automobile emissions. In contrast, the REE distribution pattern in the suspended particulate phase in rainwater was similar to that in coarse APM (diameter > 2.1 MUm), and a positive Tb anomaly was observed, suggesting that coarse particles easily become trapped in rain droplets. A negative Eu anomaly was observed in the dissolved phase in rainwater, but not in APM or in the suspended particulate phase in rainwater. Unlike other REEs, Eu can exist as both bivalent and trivalent ions in nature, and Eu-selective dissolution from or adsorption onto the trapped particles of Eu might account for the negative anomaly. These results show that atmospheric REE cycling is affected by the physico-chemical properties of APM. PMID- 22037790 TI - Monte Carlo verification of polymer gel dosimetry applied to radionuclide therapy: a phantom study. AB - This study evaluates the dosimetric performance of the polymer gel dosimeter 'Methacrylic and Ascorbic acid in Gelatin, initiated by Copper' and its suitability for quality assurance and analysis of I-131-targeted radionuclide therapy dosimetry. Four batches of gel were manufactured in-house and sets of calibration vials and phantoms were created containing different concentrations of I-131-doped gel. Multiple dose measurements were made up to 700 h post preparation and compared to equivalent Monte Carlo simulations. In addition to uniformly filled phantoms the cross-dose distribution from a hot insert to a surrounding phantom was measured. In this example comparisons were made with both Monte Carlo and a clinical scintigraphic dosimetry method. Dose-response curves generated from the calibration data followed a sigmoid function. The gels appeared to be stable over many weeks of internal irradiation with a delay in gel response observed at 29 h post preparation. This was attributed to chemical inhibitors and slow reaction rates of long-chain radical species. For this reason, phantom measurements were only made after 190 h of irradiation. For uniformly filled phantoms of I-131 the accuracy of dose measurements agreed to within 10% when compared to Monte Carlo simulations. A radial cross-dose distribution measured using the gel dosimeter compared well to that calculated with Monte Carlo. Small inhomogeneities were observed in the dosimeter attributed to non-uniform mixing of monomer during preparation. However, they were not detrimental to this study where the quantitative accuracy and spatial resolution of polymer gel dosimetry were far superior to that calculated using scintigraphy. The difference between Monte Carlo and gel measurements was of the order of a few cGy, whilst with the scintigraphic method differences of up to 8 Gy were observed. A manipulation technique is also presented which allows 3D scintigraphic dosimetry measurements to be compared to polymer gel dosimetry measurements without generating misleading errors due to the limited spatial resolution. PMID- 22037791 TI - Female sex pheromone of the Gelechiid moth Scrobipalpa salinella (Zeller). AB - The sex pheromone system of Scrobipalpa salinella (Zeller), an important pest of the halophyte Salicornia europaea in the tidal salt marshes, was studied. Z3 12:OAc and Z5-12:OAc were identified from both female pheromone glands and female emissions, but in quite different ratios. Field trapping tests demonstrated that Z3-12:OAc and Z5-12:OAc are essential for optimal attraction of male moths, and a 100:5 blend found in gland extracts is significantly more attractive to males than a 100:50 ratio similar to that found in SPME samples. Small amounts of E3 12:OAc and Z5-14:OAc also were present in pheromone gland extracts. A blend of E3 12:OAc with Z3-12:OAc attracted a few males, but was not as attractive as the binary blend of Z3-12:OAc and Z5-12:OAc. Moreover, addition of E3-12:OAc did not affect captures of males to the primary binary blend. Another glandular component, Z5-14:OAc, had no behavioral activity in field bioassays. Therefore, a synthetic mixture of Z3-12:OAc and Z5-12:OAc in a 100:5 ratio can be used as an effective tool for monitoring and control of this species. PMID- 22037792 TI - Gelatinase activity of matrix metalloproteinases during first-line chemotherapy in lung adenocarcinoma patients: an initial approach. AB - BACKGROUND: The aim of this study was to determine if gelatinase activity of plasma matrix metalloproteinases (MMPs) can be used as a method to assess chemotherapy response and cancer progression in primary lung adenocarcinoma patients. METHODS: A group of 28 patients was divided according to risk factor as follows: lung cancer associated with wood smoke exposure (LCW), lung cancer in tobacco smokers (LCT), and patients with no association to a known risk factor (LCN). Plasma gelatinase activity was measured by zymography and radiolabeled gelatin degradation. RESULTS: The chemotherapy response was better in the LCW group (25%) compared with the LCT (7.1%) patients (P = 0.039). MMP gelatinase activity was increased in all lung cancer subjects. Patients with progression of the disease had a significant increase in gelatinase activity compared with subjects, with a response to treatment (330.3 +/- 44.4 and 64.9 +/- 8.5 MUg of degraded gelatin/mg of incubated plasma protein, respectively, P = 2.972 * 10( 5)). Zymography assay revealed that the increase in gelatinase activity corresponded mainly to MMP-2. CONCLUSIONS: Patients with progression of lung adenocarcinoma, mainly from the LCT group, had an increase in gelatinase activity compared with subjects that responded to chemotherapy. Therefore, plasma gelatinase activity, particularly MMP-2 enzymatic activity, could be used as a way to assess lung adenocarcinoma progression as well as an indicator for the use of MMP-2 inhibitors. PMID- 22037794 TI - Diffuse lung disease in neurofibromatosis. AB - Prevalence, characteristics and the very existence of neurofibromatosis associated diffuse lung disease remain unclear, mostly because the few studies that looked at pulmonary involvement in such patients used chest X-ray as diagnostic mean. We report on the clinical, functional and HRCT findings in a patient with neurofibromatosis-associated diffuse lung disease and provide a short literature review. PMID- 22037793 TI - Role of thrombin-activatable fibrinolysis inhibitor in allergic bronchial asthma. AB - BACKGROUND: Bronchial asthma is an inflammatory disease of the airways. Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase that besides inhibiting fibrinolysis, also regulates inflammatory processes. The only validated substrate known for TAFI is fibrin. In the present study we evaluated the role of TAFI in bronchial asthma by comparing the development of allergic bronchial asthma between wild-type (WT) and TAFI-deficient mice (KO). METHODS: Asthmatic inflammation was induced by sensitization and challenge with ovalbumin in WT (WT/OVA) and TAFI KO (KO/OVA) mice. WT mice (WT/SAL) and TAFI KO (KO/SAL) were used as controls. Cytokines, markers of inflammation, and coagulation were measured in bronchoalveolar lavage fluid (BALF). RESULTS: Airway hyperresponsiveness was worse in KO/OVA mice than in WT/OVA mice or control mice. Markers of lung injury were significantly increased in BALF from KO/OVA mice compared to WT/OVA mice. Airway hyperresponsiveness and the BALF concentrations of IL-5 and osteopontin were significantly increased in KO/OVA mice compared to WT/OVA mice. Treatment of WT/OVA and KO/OVA mice with a C5a receptor antagonist significantly decreased hyperresponsiveness along with the BALF concentrations of total protein and C5a compared to untreated asthmatic mice. CONCLUSION: The results of this study suggest that TAFI plays a protective role in the pathogenesis of allergic inflammation probably by inhibiting the complement system. PMID- 22037795 TI - The contribution of endobronchial ultrasound-guided forceps biopsy in the diagnostic workup of unexplained mediastinal and hilar lymphadenopathy. AB - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) provides material for the cytological diagnostic workup. To improve the evaluation of unexplained intrathoracic lymphadenopathy, the availability of material for histological evaluation would be desirable. For this purpose, the technique of endobronchial ultrasound-guided mediastinal forceps biopsy (EBUS guided forceps biopsy) is a potentially good candidate. The aim of the present study was, using simple methodology, to establish the additional diagnostic yield provided by supplemental EBUS-guided forceps biopsy in comparison with EBUS-TBNA alone. METHODS: The data of 50 consecutive patients with mediastinal, lobar, and hilar space-consuming lesions were analyzed. In all patients, immediately following EBUS-TBNA with a 22-gauge needle, a 21-gauge forceps was introduced through the opening created in the bronchial wall and an EBUS-guided forceps biopsy performed. The improvement in the diagnostic yield was determined. The diagnostic yield of the EBUS-guided forceps biopsy in relation to the size of the biopsy specimen and that of the EBUS-TBNA in relation to the cell-block technique were determined. RESULTS: Combining the techniques increased the diagnostic sensitivity of the EBUS-TBNA from 50.0 to 82.0%. EBUS-guided forceps biopsies measuring >= 3 mm enabled a specific diagnosis to be established more often than did forceps biopsies <3 mm (90.9% vs. 57.1%). A cell block was prepared in 29 patients. In this case, EBUS-TBNA provided a higher diagnostic yield (65.5% vs. 28.6%) compared to cytology alone. CONCLUSION: EBUS-guided forceps biopsy should be employed for the bronchoscopic diagnosis of intrathoracic lymphadenopathy of unknown etiology. PMID- 22037796 TI - STrengthening the reporting of OBservational studies in Epidemiology-Molecular Epidemiology (STROBE-ME): an extension of the STROBE statement. AB - Advances in laboratory techniques have led to a rapidly increasing use of biomarkers in epidemiological studies. Biomarkers of internal dose, early biological change, susceptibility, and clinical outcomes are used as proxies for investigating the interactions between external and/or endogenous agents and the body components or processes. The need for improved reporting of scientific research led to influential statements of recommendations such as STrengthening Reporting of Observational studies in Epidemiology (STROBE) statement. The STROBE initiative established in 2004 aimed to provide guidance on how to report observational research. Its guidelines provide a user-friendly checklist of 22 items to be reported in epidemiological studies, with items specific to the three main study designs: cohort studies, case-control studies and cross-sectional studies. The present STrengthening the Reporting of OBservational studies in Epidemiology-Molecular Epidemiology (STROBE-ME) initiative builds on the STROBE Statement implementing 9 existing items of STROBE and providing 17 additional items to the 22 items of STROBE checklist. The additions relate to the use of biomarkers in epidemiological studies, concerning collection, handling and storage of biological samples; laboratory methods, validity and reliability of biomarkers; specificities of study design; and ethical considerations. The STROBE ME recommendations are intended to complement the STROBE recommendations. PMID- 22037797 TI - Simple and accurate alignment of toric intraocular lenses and evaluation of their rotation errors using anterior segment optical coherence tomography. AB - PURPOSE: To describe a new method of alignment of toric intraocular lenses (IOLs) and evaluation of their rotation errors using anterior segment optical coherence tomography (AS-OCT). METHODS: Twenty-nine eyes of 22 patients who had cataract extraction and implantation of an acrylic toric IOL were included. The new AS-OCT method was used for the alignment of toric IOLs and evaluation of their rotation errors. These rotation errors were evaluated and compared with those measured using the internal map of a wavefront aberrometer. RESULTS: The mean rotation error +/- standard deviation (SD) of the toric IOLs evaluated by AS-OCT was 3.2 +/- 2.2 degrees and 3.2 +/- 2.4 degrees at 1 week and 1 month after surgery, respectively. The mean difference in the reference axis between the visits was 1.8 +/- 2.1 degrees . The mean difference between the rotation errors of the alignment axes measured by AS-OCT and the internal map was 2.5 +/- 1.9 degrees (P = 0.037). CONCLUSION: The current method is clinically useful not only for the accurate alignment of toric IOLs but also for evaluating their rotation errors. PMID- 22037798 TI - Neurexins and neuroligins: recent insights from invertebrates. AB - During brain development, each neuron must find and synapse with the correct pre- and postsynaptic partners. The complexity of these connections and the relatively large distances some neurons must send their axons to find the correct partners makes studying brain development one of the most challenging, and yet fascinating disciplines in biology. Furthermore, once the initial connections have been made, the neurons constantly remodel their dendritic and axonal arbours in response to changing demands. Neurexin and neuroligin are two cell adhesion molecules identified as important regulators of this process. The importance of these genes in the development and modulation of synaptic connectivity is emphasised by the observation that mutations in these genes in humans have been associated with cognitive disorders such as Autism spectrum disorders, Tourette syndrome and Schizophrenia. The present review will discuss recent advances in our understanding of the role of these genes in synaptic development and modulation, and in particular, we will focus on recent work in invertebrate models, and how these results relate to studies in mammals. PMID- 22037799 TI - Valproic acid sensitizes human glioma cells for temozolomide and gamma-radiation. AB - Temozolomide (TMZ) is given in addition to radiotherapy in glioma patients, but its interaction with the commonly prescribed antiepileptic drug valproic acid (VPA) is largely unknown. Induction of DNA demethylation by VPA could potentially induce expression of the O(6)-methylguanine-DNA-methyltransferase (MGMT) protein, causing resistance to TMZ and thereby antagonizing its effect. Therefore, this study investigates the interaction between VPA, TMZ, and gamma-radiation. Two glioma cell lines were used that differ in TMZ sensitivity caused by the absence (D384) or presence (T98) of the MGMT protein. VPA was administered before (24/48 h) or after (24 h) single doses of gamma-radiation; or, after 24 h, VPA treatment was accompanied by a single dose of TMZ for another 24 h. For trimodal treatment the combination of VPA and TMZ was followed by single doses of gamma-radiation. In both cell lines VPA caused enhancement of the radiation response after preincubation (DMF(0.2) 1.4 and 1.5) but not after postirradiation (DMF(0.2) 1.1 and 1.0). The combination of VPA and TMZ caused enhanced cytotoxicity (DMF(0.2) 1.7) in both the TMZ-sensitive cell line (D384) and the TMZ-resistant cell line (T98). The combination of VPA and TMZ caused a significant radiation enhancement (DMF(0.2) 1.9 and 1.6) that was slightly more effective than that of VPA alone. VPA does not antagonize the cytotoxic effects of TMZ. Preincubation with VPA enhances the effect of both gamma-radiation and TMZ, in both a TMZ-sensitive and a TMZ-resistant human glioma cell line. VPA combined with TMZ may lead to further enhancement of the radiation response. PMID- 22037800 TI - Tumorigenesis and prognostic role of hepatoma-derived growth factor in human gliomas. AB - Hepatoma-derived growth factor (HDGF) is a neurotrophic factor found in mouse spinal cord and hippocampal neurons. In various malignant tumors, the role of HDGF in tumor progression and its use as a diagnostic biomarker or therapeutic target have been extensively explored. However, the prognostic function and mitogenic role of HDGF in gliomagenesis are yet to be verified. In this study, we found a significant incidence of HDGF prevalence between the different pathological types and stages of glioma in 105 patients. We also found a prognostic significance in 41 glioblastoma multiforme (GBM) patients, with prevalence of nuclear HDGF predicting short survival of patients with GBM after surgery. To delineate the mitogenic role of HDGF in gliomagenesis, an adenoviral expressed HDGF small interfering RNA (Ad-HDGF siRNA) was used to knock down expression of nuclear HDGF. After knocking down nuclear HDGF expression in human GBM cells, cell growth and cell invasion and induction on apoptosis by caspase-3 activation were significantly inhibited. We conclude that HDGF is a mitogenic growth factor in glioma progression and can be a useful prognostic marker for GBM and therapeutic target for clinical management of glioma in the future. PMID- 22037801 TI - Primary central nervous system post-transplant lymphoproliferative disorders following allogeneic hematopoietic stem cell transplantation. AB - Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Extra nodal involvement is common in PTLD, but isolated involvement of the central nervous system (CNS) is extremely rare. Given the rarity of primary CNS-PTLD there is no consensus on optimal treatment. We report a patient who developed Epstein-Barr virus related primary CNS-PTLD following allogeneic HSCT who was treated with the monoclonal anti-CD20 antibody rituximab and reduction of immunosuppression. In addition, we review the literature and discuss treatment options for patients with primary CNS-PTLD following allogeneic HSCT. PMID- 22037802 TI - Twenty years of socio-economic inequalities in type 2 diabetes mellitus prevalence in Spain, 1987-2006. AB - BACKGROUND: To analyse trends in socio-economic inequalities in the prevalence of diabetes among men and women aged >=35 years in Spain during the period 1987 2006. METHODS: We analysed trends in the age-standardized prevalence of self reported diabetes and obesity in relation to level of education using data from the Spanish National Health Survey for the years 1987, 1993, 1995, 1997, 2001, 2003 and 2006 (86 345 individuals aged >=35 years). To assess the relationship between education level and diabetes and obesity, we computed the Slope Index of Inequality and the Relative Index of Inequality (RII) for each year. Additional models were fit to take into account mediator variables in socio-economic position (SEP) diabetes inequalities. RESULTS: The prevalence of self-reported diabetes was higher among persons of low educational level, increasing more rapidly over time among people with lower education level (5.0-12.6% in men, and 8.4-13.1% in women between 1987 and 2006) than among those with higher education level (6.3-8.7% in men and 3.8-4.0% in women). Relative inequalities showed a weak tendency to increase. In women, the RII of self-reported diabetes increased from 3.04 (1.95-4.74) in 1987 to 4.28 (2.98-6.13) in 2006, while in men were constant since 1993. Trends in SEP inequalities in diabetes prevalence were attenuated when mediator variables were taken into account in women but not in men. CONCLUSION: SEP inequalities in diabetes existed >20 years ago and have increased, especially among women. These patterns may be explained by trends in health behaviours and obesity, but only to a limited extent. PMID- 22037803 TI - Limitations to functioning and independent living after the onset of coronary heart disease: what is the role of lifestyle factors and obesity? AB - BACKGROUND: People with coronary disease have a higher risk of functional limitations than their same-age counterparts without disease. This study examined prospectively the extent to which functioning and independent living among individuals with coronary disease in early old age are associated with lifestyle factors before and after disease onset. METHODS: Participants were 986 British civil servants (657 men and 329 women aged 35-55 years), who were free of coronary disease at study entry in 1985-88 but developed disease during 21 years follow-up (the Whitehall II study). Lifestyle factors (obesity, smoking, alcohol, diet and physical activity) were measured at baseline and follow-up in 2007-09. Post-disease limitations to functioning were measured in 2006-09 at mean age is 68 years using activities of daily living scales. RESULTS: Low physical activity and being overweight [body mass index (BMI) >=25] before and after disease onset were associated with having one or more limitations in activities of daily living among coronary patients [age-, sex- and socio-economic position adjusted odds ratios for pre-disease inactivity and obesity 1.53 [95% confidence interval (95% CI) 0.99-2.35] and 2.53 (95% CI 1.53-4.18), respectively]. A decrease in physical activity [odds ratio (OR): 2.42, 95% CI 1.59-3.68] and an increase of >5 U in BMI (OR: 2.05, 95% CI 1.34-3.13) were also related to limitations in activities of daily living after disease onset. These relationships were not accounted for by measured co-morbidities. No robust associations were observed for smoking, alcohol use and diet. CONCLUSION: Physical activity and weight control across the adult life course are associated with fewer limitations to functioning and independent living after the onset of coronary disease. PMID- 22037805 TI - Size distribution and seasonal variation of airborne particulate matter in five areas in Istanbul, Turkey. AB - GOAL, SCOPE, AND BACKGROUND: Many studies have focused on measuring fine and course particulate matter (PM) in urban and rural sites around the world. The aim of this research is to gain information on the size distribution of particles. The physical characteristics of PM in the urban air of Istanbul were determined. METHODS: PM sampling was carried out at five stations (Avcilar, Besiktas, Kilyos, Rasathane, and Goztepe) over a period of 2 years. PM filter samples were collected for eight different size ranges (<0.43, 0.43-1, 1-1.7, 1.7-2.6, 2.6 3.5, 3.5-5.2, 5.2-6.5, 6.5-8, and >8 MUm) using a Cascade Impactor. The size distributions of the PM samples were determined. RESULTS AND DISCUSSION: The mean total PM concentrations were 48.6 +/- 34.0, 34.8 +/- 11.6, 28.6 +/- 13.6, 21.5 +/ 9.1, and 16.8 +/- 5.1 MUg/m(3) for the Goztepe, Besiktas, Avcilar, Rasathane, and Kilyos stations, respectively. The total PM concentrations were found to be 1.2-1.5 times higher in the fall and winter than in the spring and summer, except for at the station in Avcilar. The PM concentrations in Avcilar did not exhibit seasonal variations. This is thought to result from the intense industrial activity in the area. PM(2.6) (below 2.6 MUm particles) comprised up to 62% of the total amount of PM in samples collected at the Goztepe, Besiktas, and Rasathane stations during the fall and winter. PM(1) was determined to be approximately 45% of the total, corresponding to 57% of the amount of PM(2.5). A multi-modal PM size distribution was observed. The lowest Mass Median Aerodynamic Diameter (MMAD) values observed in Avcilar, Besiktas, Rasathane, and Goztepe were 4.2, 3.9, 2.9, and 3.5 MUm, respectively, and were observed during the season of active household heating. No difference was measured in the MMAD values (5.2 MUm) between the seasons of heating and non-heating in Kilyos. PMID- 22037806 TI - Identification and evaluation of air-pollution-tolerant plants around lignite based thermal power station for greenbelt development. AB - INTRODUCTION: Thermal power plants emit various gaseous and particulate pollutants into the atmosphere. It is well known that trees help to reduce air pollution. Development of a greenbelt with suitable plant species around the source of emission will mitigate the air pollution. Selection of suitable plant species for a greenbelt is very important. MATERIALS AND METHODS: Present study evaluates different plant species around Neyveli thermal power plant by calculating the Air Pollution Tolerance Index (APTI) which is based on their significant biochemical parameters. Also Anticipated Performance Index (API) was calculated for these plant species by combining APTI values with other socio economic and biological parameters. DISCUSSION: Based on these indices, the most appropriate plant species were identified for the development of a greenbelt around the thermal power plant to mitigate air pollution. Among the 30 different plant species evaluated, Mangifere indica L. was identified as keystone species which is coming under the excellent category. CONCLUSION: Ambient air quality parameters were correlated with the biochemical characteristics of plant leaves and significant changes were observed in the plants biochemical characteristics due to the air pollution stress. PMID- 22037807 TI - Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine. AB - The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release. PMID- 22037808 TI - Chronic Achilles tendon rupture reconstruction using a free semitendinosus tendon graft transfer. AB - PURPOSE: The purpose of this study was to evaluate the outcomes following reconstruction of the chronic Achilles tendon ruptures with large gaps (>6 cm) using free semitendinosus tendon graft transfer. METHODS: There were 11 consecutive patients underwent the above-mentioned surgical technique for the treatment of chronically ruptured Achilles tendon contributed in current study and were followed up prospectively for a mean of 25 +/- 3 months. The intraoperative tendon defect was greater than 6 cm in all of the patients. Functional and clinical assessment was performed using The American Orthopaedic Foot and Ankle Society (AOFAS) and Achilles Tendon Rupture Score (ATRS). RESULTS: The average AOFAS and ATRS improved significantly from 70 +/- 5 and 32 +/- 6 preoperatively, to 92 +/- 5 and 89 +/- 4 points post-operatively (P = 0.001). The range of dorsiflexion was significantly limited on the operated side (13 +/- 4 degrees vs. 17 +/- 4 degrees ) (P = 0.04). All patients were able to stand on the tiptoe of injured leg, and no patient walked with a visible limp. Post operative complications included one patient with symptomatic DVT and 2 patients with superficial infection treated nonoperatively. CONCLUSIONS: The technique offers good clinical and functional outcomes and is safe. Reconstruction of the chronic Achilles tendon ruptures with free semitendinosus tendon graft in patients with defects greater than 6 cm is recommended. LEVEL OF EVIDENCE: IV. PMID- 22037809 TI - Non-surgical management of early knee osteoarthritis. AB - Conservative approach is usually the first choice for the management of the knee degeneration processes, especially in the phase of the disease recognized as early osteoarthritis (OA) with no clear lesions or associated abnormalities requiring to be addressed surgically. A wide spectrum of treatments is available, from non-pharmacological modalities to dietary supplements and pharmacological therapies, as well as minimally invasive procedures involving injections of various substances aiming to restore joint homeostasis and provide clinical improvement and possibly a disease-modifying effect. Numerous pharmaceuticals have been proposed, but since no therapy has shown all the characteristic of an ideal treatment, and side effects have been reported at both systemic and local level, the use of pharmacological agents should be considered with caution by assessing the risk/benefit ratio of the drugs prescribed. Both patients and physicians should have realistic outcome goals in pharmacological treatment, which should be considered together with other conservative measures. A combination of these therapeutic options is a more preferable scenario, in particular considering the evidence available for non-pharmacological management. In fact, exercise is an effective conservative approach, even if long-term effectiveness and optimal dose and administration modalities still need to be clarified. Finally, physical therapies are emerging as viable treatment options, and novel biological approaches are under study. Further studies to increase the limited medical evidence on conservative treatments, optimizing results, application modalities, indications, and focusing on early OA will be necessary in the future. Level of evidence IV. PMID- 22037811 TI - Muscle strength and functional performance in patients at high risk of knee osteoarthritis: a follow-up study. AB - PURPOSE: To investigate whether changes from 2 to 4 years post arthroscopic partial meniscectomy (APM) in mechanical muscle function and objectively measured function differ between the operated and contra-lateral leg of APM patients or compared with controls. METHODS: Twenty-two patients (age 46.6 +/- 5.0, BMI 24.7 +/- 2.9) and 25 controls (age 46.4 +/- 5.2, BMI 25.1 +/- 4.6) previously examined at ~2 years post APM were examined again at ~4 years post surgery for maximal knee extensor/flexor voluntary contraction (MVC) and rapid force capacity. Functional performance was assessed by the distance achieved during a one-leg hop test and the maximum number of knee bends performed in 30 s. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to evaluate self-reported outcomes. RESULTS: Overall changes from 2 to 4 years post APM did not differ in maximal muscle strength, rapid force capacity, and functional performance between the operated and contra-lateral leg of patients or control legs. However, secondary analysis showed a difference in change in knee extensor MVC resulting in a 6% difference between the operated and contra-lateral leg of patients at follow-up. CONCLUSIONS: No differences in longitudinal changes were observed from 2 to 4 years post APM between patients and controls. The secondary finding of differential changes over time in knee extensor MVC between the operated and contra-lateral leg partly confirm our hypothesis that differences in muscle strength may evolve from 2 to 4 years post APM. This differential change may represent an initial sign of an evolving lower limb muscle asymmetry, which may play a role in the development of knee OA. LEVEL OF EVIDENCE: III. PMID- 22037812 TI - Quantitative magnetic resonance imaging (MRI) morphological analysis of knee cartilage in healthy and anterior cruciate ligament-injured knees. AB - PURPOSE: To analyze the morphological change in the cartilage of the knee after anterior cruciate ligament (ACL) injury by comparing with that of the intact contralateral knee. METHODS: A total of 22 participants (12 male and 10 female patients) who had unilateral ACL injury underwent MRI scan of both the injured and intact contralateral knees. Sagittal plane images were segmented using a modeling software to determine cartilage volume and cartilage thickness in each part of the knee cartilage that were compared between the ACL-injured and the intact contralateral knees. Furthermore, the male and female patients' data were analyzed in subgroups. RESULTS: The ACL-injured knees had statistically significant lower total knee cartilage volume than the intact contralateral knees (P = 0.0020), but had similar mean thickness of total knee cartilage (not significant: n.s.). In the male subgroup, there was no significant difference in cartilage volume and thickness between normal and ACL-injured knees. In the female subgroup, the ACL-injured knees demonstrated statistically significant difference in total knee cartilage volume (P = 0.0004) and thickness (P = 0.0024) compared with the normal knees. The percentage change in the cartilage thickness in women was significantly greater than that in men. CONCLUSION: Cartilage volume was significantly smaller in the ACL-injured knees than in the contralateral intact knees in this cohort. Women tended to display greater cartilage volume and thickness change after ACL injury than men. These findings indicated that women might be more susceptible to cartilage alteration after ACL injuries. LEVEL OF EVIDENCE: III. PMID- 22037813 TI - The effect of local anesthetic and corticosteroid combinations on chondrocyte viability. AB - PURPOSE: Local anesthetic and corticosteroid combination injections are often used in clinical practice, however research investigating the chondrotoxic properties of these combinations is minimal. The goal of this study was to evaluate the effect of single injection doses of 1% lidocaine or 0.25% bupivacaine in combination with single injection doses of dexamethasone sodium phosphate (Decadron), methylprednisolone acetate (Depo-Medrol), betamethasone sodium phosphate and betamethasone acetate (Celestone Soluspan), or triamcinolone acetonide (Kenalog) on human chondrocyte viability. METHODS: All treatment conditions were delivered to human chondrocytes in vitro for the medication's respective average duration of action using a bioreactor containing a continuous infusion pump constructed to mimic joint fluid metabolism. A two-color fluorescence assay was used to evaluate cell viability. A mixed-effects regression model was used to evaluate the mean differences in cell viability between treatment groups. RESULTS: At 14 days, a single injection dose of 1% lidocaine or 0.25% bupivacaine in combination with betamethasone sodium phosphate and betamethasone acetate solution illustrated significant chondrotoxicity when compared with the local anesthetics alone (P < 0.01). Methylprednisolone acetate and Triamcinolone acetonide both showed significant evidence of chondrotoxicity (P = 0.013; P = 0.016, respectively) when used in combination with 1% lidocaine compared with lidocaine alone, but showed no significant chondrotoxicity in combination with 0.25% bupivacaine (P's = n.s.). CONCLUSIONS: Clinicians should use caution when injecting 1% lidocaine or 0.25% bupivacaine in conjunction with betamethasone sodium phosphate and betamethasone acetate solution due to its pronounced chondrotoxic effect in this study. 1% lidocaine used in combination with methylprednisolone acetate or triamcinolone acetonide also led to significant chondrotoxicity. PMID- 22037814 TI - Effect of tracer dose on left ventricular mechanical dyssynchrony indices by phase analysis of gated single photon emission computed tomography myocardial perfusion imaging. AB - BACKGROUND: There are limited data on the effect of tracer dose on the reproducibility and accuracy of left ventricular (LV) mechanical dyssynchrony indices by phase analysis of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS AND RESULTS: We measured LV dyssynchrony in 54 patients with normal LV ejection and perfusion (group 1) and 54 age and gender matched patients with LV ejection <35% (group 2) using phase analysis of gated SPECT MPI from stress (high dose) and rest (low dose) studies with 2 software programs: Corridor4DM (4DM) and Emory Cardiac Toolbox (ECTb). Although the correlation between rest- and stress-derived standard deviation was good (R = 0.76, P < .0001, with both software programs), there was considerable variability between the measurements (P < .0001 by paired t test). In addition, the rest standard deviation was significantly higher than stress in group 1 (10.2 degrees +/- 4.6 degrees vs 6.1 degrees +/- 2.5 degrees , and 12.2 degrees +/- 6.4 degrees vs 7.9 degrees +/- 4.6 degrees , with 4DM and ECTb, respectively, P < .0001 for both) and group 2 patients (44.0 degrees +/- 18.0 degrees vs 35.9 degrees +/- 21.0 degrees and 47.3 degrees +/- 19.2 degrees vs 38.8 degrees +/- 19.8 degrees , with 4DM and ECTb, P = .03 and .02, respectively). Similarly, the rest standard deviations were higher than the stress values irrespective of the type of stress test (i.e., exercise vs pharmacological), and the body mass index. Finally, using rest-derived dyssynchrony indices was associated with 9% 13% and 22%-26% false positive rate of significant mechanical dyssynchrony using different cut-off values for groups 1 and 2, respectively. CONCLUSION: LV mechanical dyssynchrony indices by phase analysis have more variation and are significantly higher if derived from rest gated SPECT images obtained with low dose tracer. PMID- 22037815 TI - The cherished doctor-patient relationship: a personal reflection. PMID- 22037816 TI - [Congenital self-healing Langerhans cell histiocytosis]. AB - A male infant, born at term after an uncomplicated pregnancy, presented with multiple red-brown papules and nodules spread over his body. The infant's general condition was not affected and there was no systemic involvement. After only 6 weeks the lesions had healed completely without recurrence. Based on histological and immunohistochemical findings, the clinical appearance and the self-healing course, the diagnosis of congenital self-healing Langerhans cell histiocytosis was established. PMID- 22037817 TI - [Fungal nail infections--an update: Part 1--Prevalence, epidemiology, predisposing conditions, and differential diagnosis]. AB - Onychomycosis describes a chronic fungal infection of the nails most frequently caused by dermatophytes, primarily Trichophyton rubrum. In addition, yeasts (e. g. Candida parapsilosis), more rarely molds (Scopulariopsis brevicaulis), play a role as causative agents of onychomycosis. However, in every case it has to be decided if these yeasts and molds are contaminants, or if they are growing secondarily on pathological altered nails. The point prevalence of onychomycosis in Germany is 12.4%, as demonstrated within the "Foot-Check-Study", which was a part of the European Achilles project. Although, onychomycosis is rarely diagnosed in children and teens, now an increase of fungal nail infections has been observed in childhood. More and more, diabetes mellitus becomes important as significant disposing factor both for tinea pedis and onychomycosis. By implication, the onychomycosis represents an independent and important predictor for development of diabetic foot syndrome and foot ulcer. When considering onychomycosis, a number of infectious and non-infectious nail changes must be excluded. While psoriasis of the nails does not represent a specific risk factor for onychomycosis, yeasts and molds are increasing isolated from patients with psoriatic nail involvement. In most cases this represents secondary growth of fungi on psoriatic nails. Recently, stigmatization and impairment of quality of life due to the onychomycosis has been proven. PMID- 22037818 TI - [Fungal nail infections - an update. Part 2 - From the causative agent to diagnosis - conventional and molecular procedures]. AB - Trichophyton (T.) rubrum is the most frequently isolated dermatophyte in onychomycosis, both in Germany and worldwide. T. interdigitale (formerly T. mentagrophytes var. interdigitale) follows in second place. A further however rarely isolated dermatophyte in onychomycosis is Epidermophyton floccosum. Candida parapsilosis, Candida guilliermondii, and Candida albicans, followed by Trichosporon spp. are the most important yeasts which are found in onychomycosis. The molds most often responsible include Scopulariopsis brevicaulis, and several Aspergillus species, e. g. Aspergillus versicolor, and Fusarium spp. These so called non-dermatophyte molds (NDM) are increasingly isolated as emerging pathogens in onychomycosis. The diagnosis of onychomycosis should be verified in the mycology laboratory. Conventional diagnostic methods include the direct examination, ideally using fluorescence staining with Calcofluor(r) or Blancophor(r), and culture. However, new molecular biological methods primarily employing the polymerase chain reaction (PCR) for direct detection of dermatophyte DNA in skin scrapings and nail samples have been introduced into routine mycological diagnostics. The diagnostic sensitivity is higher when both conventional and molecular procedures are combined. PMID- 22037819 TI - Environmental fate of fungicides in surface waters of a horticultural-production catchment in southeastern Australia. AB - Fungicides are regularly applied in horticultural production systems and may migrate off-site, potentially posing an ecological risk to surface waterways. However, few studies have investigated the fate of fungicides in horticultural catchments. This study investigated the presence of 24 fungicides at 18 sites during a 5-month period within a horticultural catchment in southeastern Australia. Seventeen of the 24 fungicides were detected in the waterways, with fungicides detected in 63% of spot water samples, 44% of surface sediment samples, and 44% of the passive sampler systems deployed. One third of the water samples contained residues of two or more fungicides. Myclobutanil, trifloxystrobin, pyrimethanil, difenoconazole, and metalaxyl were the fungicides most frequently detected, being present in 16-38% of the spot water samples. Iprodione, myclobutanil, pyrimethanil, cyproconazole, trifloxystrobin, and fenarimol were found at the highest concentrations in the water samples (> 0.2 MUg/l). Relatively high concentrations of myclobutanil and pyrimethanil (>= 120 MUg/kg dry weight) were detected in the sediment samples. Generally the concentrations of the fungicides detected were several orders of magnitude lower than reported ecotoxicological effect values, suggesting that concentrations of individual fungicides in the catchment were unlikely to pose an ecological risk. However, there is little information on the effects of fungicides, especially fungi and microbes, on aquatic ecosystems. There is also little known about the combined effects of simultaneous low-level exposure of multiple fungicides to aquatic organisms. Further research is required to adequately assess the risk of fungicides in aquatic environments. PMID- 22037820 TI - Predicting the toxicity of permethrin to Daphnia magna in water using SPME fibers. AB - Multiple factors can influence bioavailability, which can make predictions of toxicity in natural systems difficult. The current study examined the potential use of solid-phase microextraction fibers as a matrix-independent approach to predict the toxicity of permethrin to Daphnia magna across various water sources, including a laboratory reconstituted water, two natural waters, and a modified natural water. Water source strongly affected the toxicity of permethrin as well as the concentration-response relationships. Although permethrin concentrations in the water were predictive of toxicity to D. magna for individual water sources, there was no relationship between permethrin concentrations among water sources and mortality. This indicated that compositional differences among water sources can greatly influence toxicity, suggesting that benchmarks established using reconstituted water may be overly conservative for some natural waters. In addition, although permethrin tissue residues were predictive of mortality for individual waters, the correlation among waters was not as clear. Finally, both 48-h and equilibrium-based SPME fiber concentrations adequately predicted toxicity independent of water properties. This demonstrated that bioavailability based estimates provided a more accurate prediction of toxicity than water concentrations and that SPME fibers could be used in environmental monitoring as a rapid and accurate means of predicting toxicity in natural waters. PMID- 22037821 TI - Morphological assessments on the arteries of the superior renal segment. AB - The study was performed on 461 renal arteries in order to assess some morphological aspects regarding the arteries that supply the superior renal segment using as study methods: dissection, injection of contrast medium, injection of plastic followed by corrosion together with the examination of MRI and renal angiographies (simple and angio CT). The posterior arteries of the superior renal segment originate mostly from the posterior terminal branch of the renal artery as 1-3 arterial branches. In only 42 cases, we found posterior branches that do not participate in the supply of the superior renal pole. In 190 cases, the anterior arteries of the superior segment originated from the anterior division of the renal artery and in 73 cases directly from the trunk of the renal artery. 34 cases were assessed as a terminal division of the renal artery, while the origin from the posterior division of the renal artery was encountered in 18 cases. In 138 cases, the artery of the superior segment originated from a supplementary renal artery, double (118 cases) or triple (20 cases); in this situation, from the polar artery started the inferior suprarenal artery, except five cases where it originated from the aorta. Of the total of 461 samples, in 244 cases the renal approach was performed above the renal hilum, as proper superior polar arteries and in 217 cases the artery entered through the upper part of the hilum as an apical artery. The morphology of the arteries of the superior renal segment shows a significant degree of variability mostly in what concerns the anterior ones. Frequently we encountered a clear delimitation of the superior renal segment (in 61% of the cases), a situation that allows a relatively facile nephrectomy. PMID- 22037822 TI - Empirical therapy with ceftazidime combined with levofloxacin or once-daily amikacin for febrile neutropenia in patients with neoplasia: a prospective comparative study. AB - Combination antimicrobial therapy represents common practice in the treatment of febrile neutropenia aiming to broaden the antimicrobial spectrum against Gram negative pathogens. We did a prospective, non-randomized, comparative study to evaluate ceftazidime plus either levofloxacin or once-daily amikacin as empirical regimens for febrile neutropenia in patients with solid tumor or hematopoietic neoplasm in a region of high baseline resistance prevalence. We included 285 febrile neutropenic episodes in 235 individual patients. One hundred forty-eight cases received levofloxacin and 137 received amikacin, both in combination with ceftazidime. More cases in the levofloxacin than the amikacin group had underlying hematological malignancy; most other characteristics of the two groups were well balanced. Nephrotoxicity requiring treatment discontinuation occurred in one case in the amikacin group. No difference in clinical success (79.7% vs. 80.3%, p>0.99) or all-cause mortality (12.8% vs. 11.7%, p=0.86) was noted between the levofloxacin and the amikacin groups, even after adjustment for the independent predictor variables for each endpoint. Sepsis at presentation, presence of localizing symptoms/signs of infection, and isolation of a non susceptible Gram-negative pathogen independently predicted both clinical success and all-cause mortality. Additionally, underlying solid tumor independently predicted clinical success, while poor prognosis of the underlying neoplasia and skin/soft tissue infection independently predicted mortality. Ceftazidime plus levofloxacin had similar effectiveness to ceftazidime plus amikacin as empirical regimens for febrile neutropenia. Nephrotoxicity with once-daily amikacin was minimal. Inappropriate empirical therapy was associated with worse prognosis. PMID- 22037823 TI - Insights into Candida tropicalis nosocomial infections and virulence factors. AB - Candida tropicalis is considered the first or the second non-Candida albicans Candida (NCAC) species most frequently isolated from candidosis, mainly in patients admitted in intensive care units (ICUs), especially with cancer, requiring prolonged catheterization, or receiving broad-spectrum antibiotics. The proportion of candiduria and candidemia caused by C. tropicalis varies widely with geographical area and patient group. Actually, in certain countries, C. tropicalis is more prevalent, even compared with C. albicans or other NCAC species. Although prophylactic treatments with fluconazole cause a decrease in the frequency of candidosis caused by C. tropicalis, it is increasingly showing a moderate level of fluconazole resistance. The propensity of C. tropicalis for dissemination and the high mortality associated with its infections might be strongly related to the potential of virulence factors exhibited by this species, such as adhesion to different host surfaces, biofilm formation, infection and dissemination, and enzymes secretion. Therefore, the aim of this review is to outline the present knowledge on all the above-mentioned C. tropicalis virulence traits. PMID- 22037824 TI - Gestational diabetes: implications for cardiovascular health. AB - Gestational diabetes mellitus (GDM) is a pregnancy complication that is becoming more prevalent with recent population trends in obesity and advancing maternal age. A diagnosis of GDM not only increases risk for maternal and fetal complications during pregnancy, but also significantly increases a woman's risk of both type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in the postpartum. Even women with milder forms of abnormal glucose homeostasis during pregnancy, specifically gestational impaired glucose tolerance, are at increased risk, justifying the recent recommendation to tighten the diagnostic criteria for GDM, thus implicating many more women. Risk factors that increase risk for future CVD among women with a history of GDM include postpartum progression to T2DM; metabolic syndrome; obesity; hypertension; and altered levels of circulating inflammatory markers, specifically, adiponectin, C-reactive protein, and tumor necrosis factor-alpha. Medical therapies such as metformin that prevent progression to T2DM may prove to be our primary defense against earlier CVD among women with GDM. PMID- 22037825 TI - Molecular differentiation of Culicoides biting midges (Diptera: Ceratopogonidae) from the subgenus Culicoides Latreille in Denmark. AB - Identification of Culicoides biting midges to species has attracted attention due to the recent outbreak of bluetongue disease in Northern Europe. Identification of Culicoides to species level has been based on morphological characters and is difficult as several species belonging to species complexes are hard to distinguish. We evaluated the use of the mitochondrial DNA cytochrome oxidase I gene (COI) barcode region in the identification of species within the subgenus Culicoides. COI barcode sequence divergence within species was <1%, whereas it ranged from 12.5% to 19.8% between subgenus Culicoides species. The divergence of subgenus Culicoides species to C. nubeculosus from the subgenus Monoculicoides ranged from 24.4% to 26.1%. Specimens were differentiated into eight unique clusters, including the four common Palaearctic species Culicoides punctatus, Culicoides pulicaris, Culicoides impunctatus, and Culicoides grisescens. Additionally, this study confirms the existence of Culicoides halophilus as a valid taxon and presents the first Culicoides deltus barcode sequences. Three additional groups of specimens were identified: Culicoides dk1 with a COI barcode diverging by 14.3% to 17.2% from other subgenus Culicoides species and Culicoides Kalix and Culicoides dk3, which diverged by 5.9% from each other and showed 12.5% to 17.6% divergence in COI barcode to subgenus Culicoides specimens. PMID- 22037826 TI - In vitro amoebicidal activities of Teucrium polium and T. chamaedrys on Acanthamoeba castellanii trophozoites and cysts. AB - Amoebic keratitis is difficult to treat without total efficacy in some patients because of cysts, which are less susceptible than trophozoites to the usual treatments. The aim of this study is to evaluate the in vitro amoebicidal activity of the methanolic extracts of Teucrium polium and Teucrium chamaedrys. In the presence of methanolic extracts (ranging from 1.0 to 32.0 mg/ml), numbers of the viable Acanthamoeba castellani trophozoites and cysts were decreased during the experimental process. Both extracts showed time- and dose-dependent amoebicidal action on the trophozoites and cysts. Among the extracts tested, T. chamaedrys showed the strongest amoebicidal effect on the trophozoites. In the presence of 16 mg/ml or above extract concentrations, no viable trophozoites were observed within 48 h. In the case of T. polium, no viable trophozoites were observed within 48 h at 32 mg/ml concentration. As expected, cysts were found more resistant to the extracts than the trophozoites. PMID- 22037827 TI - In vitro antileishmanial and antitrypanosomal activities of five medicinal plants from Burkina Faso. AB - After ethnobotanical surveys in central and western regions of Burkina Faso, five plants namely Lantana ukambensis (Verbenaceae), Xeoderris sthulmannii (Fabaceae), Parinari curatellifollia (Chrysobalanaceae), Ozoroa insignis (Anacardiaceae), and Ficus platyphylla (Moraceae) were selected for their traditional use in the treatment of parasitic diseases and cancer. Our previous studies have focused on the phytochemical, genotoxicity, antioxidant, and antiproliferative activities of these plants. In this study, the methanol extract of each plant was tested to reveal probable antileishmanial and antitrypanosomal activities. Colorimetric and spectrophotometric methods were used for the detection of antileishmanial and antitrypanosomal activities. Leishmania donovani (LV9 WT) and Trypanosoma brucei brucei GVR 35 were used to test the antileishmanial and antitrypanosomal activities, respectively. All extracts of tested plants showed a significant antitrypanosomal activity with minimum lethal concentrations between 1.5 and 25 MUg/ml, the L. ukambensis extract being the most active. In the antileishmanial test, only the extract from L. ukambensis showed significant activity with an inhibitory concentration (IC(50)) of 6.9 MUg/ml. The results of this study contribute to the promotion of traditional medicine products and are preliminary for the isolation of new natural molecules for the treatment of leishmaniasis and trypanosomiasis. PMID- 22037828 TI - Polymorphisms in cycloxygenase-2 gene and breast cancer prognosis: association between PTGS2 haplotypes and histopathological features. AB - Cyclooxygenase-2 (COX-2) overexpression is associated with worse prognosis in breast cancer. COX-2 is encoded by a polymorphic gene, called PTGS2, and its expression may be genetically influenced. In this article, we investigate the association between PTGS2 haplotypes and histopathological parameters with prognostic value on the clinical outcome of breast cancer. The study involved 606 women under current treatment for non-metastatic breast cancer. Patients were genotyped for rs689465, rs689466, rs20417, and rs5275, and their haplotypes were inferred. The distribution of PTGS2 genotypes and haplotypes was evaluated according to histopathological categorical groups used for prognostic determination of low/intermediate versus high risk of tumor recurrence. Our results indicate positive associations between variant genotypes of rs689465 and estrogen receptor negativity (OR: 1.59, 95% CI: 1.04-2.44, P: 0.02) or HER2 positivity (OR: 1.79, 95% CI: 1.00-3.18, P: 0.03), and between variant genotypes of rs20417 and estrogen receptor negativity (OR: 1.75, 95% CI: 1.15-2.57, P: 0.005), progesterone receptor negativity (OR: 1.56, 95% CI: 1.09-2.22, P: 0.01) or HER2 positivity (OR: 1.80, 95% CI: 1.04-3.13, P: 0.02). In contrast, variant genotypes of rs689466 are negatively associated with estrogen receptor negativity (OR: 0.57, 95% CI: 0.33-0.98, P: 0.03). A total of eight haplotypes were inferred, and there was a significant difference in their distribution as a function of tumor size (P: 0.011), estrogen receptor status (P: 0.018), and HER2 status (P: 0.025). PTGS2 haplotype *7 (formed by rs689465G, rs689466A, rs20417C, and rs5275T) is positively associated with higher tumor size (OR: 3.72, 95% CI: 1.19-11.22, P: 0.006), estrogen receptor negativity (OR: 2.43, 95% CI: 0.97-5.98, P: 0.032), progesterone receptor negativity (OR: 2.58, 95% CI: 1.05-6.39, P: 0.02), and HER2 positivity (OR: 4.17, 95% CI: 1.19-14.44, P: 0.007). Our results suggest that PTGS2 haplotype *7 may contribute to higher growth of untreated breast cancer and that PTGS2 haplotypes need to be considered in the characterization of breast cancer prognosis. PMID- 22037829 TI - The association between mammographic density measures and aspirin or other NSAID use. AB - There is evidence that aspirin use reduces the risk of breast cancer. Increased mammographic density is known to be associated with increased breast cancer risk. Little is known about the association between mammographic density and aspirin or other non-steroidal anti-inflammatory drug (NSAID) use, but it is possible that the association between aspirin use and breast cancer risk might be due to the effect of aspirin on mammographic density. Multiple linear regression was used to investigate the association between measures of mammographic density and the use, frequency, and duration of aspirin and other NSAIDs such as paracetamol (acetaminophen), arthritis medication, and other over-the-counter or doctor prescribed pain medications in 3286 women from the Australian Mammographic Density Twins and Sisters Study and the Genes Behind Endometriosis Study. We found no association between either dense area or percent dense area with any of the NSAIDs examined (all P > 0.06). If aspirin is reducing the breast cancer risk in women, it is likely doing so via a different pathway other than mammographic density measures that predict breast cancer risk. PMID- 22037830 TI - Preprocedural planning with prospectively triggered multidetector row CT angiography prior to bronchial artery embolization in cystic fibrosis patients with massive hemoptysis. AB - STUDY OBJECTIVES: The aim of this study was to determine if electrocardiographically synchronized, prospectively triggered multidetector row computed tomography (ECG-MDR-CT) angiography of the aorta can accurately predict the location of ectopic bronchial arteries in patients with cystic fibrosis (CF) with massive hemoptysis prior to bronchial artery embolization (BAE). DESIGN AND SETTING: The study was a prospective, observational study from September 1, 2009 to June 30, 2011, conducted at a university hospital with an adult CF center. PATIENTS: The study included adult CF patients with massive hemoptysis. RESULTS: A total of four adult patients (mean [+/- SD] age = 31.5 +/- 7.9 years) with CF and massive hemoptysis underwent ECG-MDR-CT angiography. The location of the bleeding source was predicted in each case based on lung pathology observed on ECG-MDR-CT angiography. All four patients eventually required BAE without the need for conventional aortograms since the locations of the bronchial arteries were determined prior to the procedure. Review of lung pathology and arterial networks from the ECG-MDR-CT angiography data limited the number of selective catheterizations necessary to complete the procedures. BAE resulted in complete resolution of hemoptysis in three patients and successful mitigation of the bleeding in the fourth patient until lung transplantation was performed 1 week later. CONCLUSIONS: ECG-MDR-CT angiography accurately depicted bronchial artery anatomy in CF patients with massive hemoptysis and provided excellent preprocedural planning for BAE. The information provided by ECG-MDR-CT angiography of the aorta prior to conventional angiography decreased the BAE radiation dose and contrast volume and likely reduced table time. PMID- 22037831 TI - Structural colored fiber fabricated by a facile colloid self-assembly method in micro-space. AB - Structural colored fiber was fabricated by an isothermal heating evaporation induced self-assembly method. Under ambient white light illumination, the fibers appear colored due to optical reflectance, which is determined by the lattice constants of the photonic crystals. By controlling the size and layers of the silica nanospheres, the fiber color can be changed. PMID- 22037832 TI - The role of intermolecular interactions in solid state fluorescent conjugated polymer chemosensors. AB - A functionalized fluorescent conjugated polymer, tolylterpyridine poly(p phenyleneethynylene-thienyleneethynylene (ttp-PPETE), was designed and synthesized to detect trace amounts of toxic transition metal pollutants in ground water. Photophysical studies in tetrahydrofuran (THF) successfully demonstrated this polymer as a selective and sensitive chemosensor for Ni(2+) and Co(2+) in aqueous solution. Solid state composites of these chemosensors have now been prepared which can be modified to provide for inexpensive and portable field based chemical detection. A solid composite of ttp-PPETE, blended with poly (methyl methacrylate) shows UV-vis absorption and fluorescence emission spectra which are red- shifted when compared to solution phase spectra, suggesting an increase in conjugation in the solid state. An additional absorption peak, not present in solution, is also observed in the solid state. The presence of this new peak provides evidence of interacting FCP chains in the solid state. Concentration dependent experiments were done on the solid composite showing red shifted emission peaks accompanied by a significant reduction in the fluorescent quantum yield. These observations are consistent with the formation of aggregated polymer species in the solid state. Intermolecular interactions of this type can be manipulated in the design of sensitive and selective solid state fluorescent conjugated polymer sensors. PMID- 22037833 TI - Studies on curcumin and curcuminoids. XLVI. Photophysical properties of dimethoxycurcumin and bis-dehydroxycurcumin. AB - The steady-state absorption and fluorescence, as well as the time-resolved fluorescence properties of dimethoxycurcumin and bis-dehydroxycurcumin dissolved in several solvents differing in polarity and H-bonding capability are presented. The singlet oxygen generation efficiency of the two compounds relative to curcumin is estimated. The photodegradation quantum yield of the former compound in acetonitrile and methanol is determined. The dimethoxycurcumin and bis dehydroxycurcumin decay mechanisms from the S (1) state are discussed and compared with those of curcumin, dicinnamoylmethane and bis-demethoxycurcumin. PMID- 22037834 TI - Field comparison of three inhalable samplers (IOM, PGP-GSP 3.5 and Button) for welding fumes. AB - Inhalable sampler efficiency depends on the aerodynamic size of the airborne particles to be sampled and the wind speed. The aim of this study was to compare the behaviour of three personal inhalable samplers for welding fumes generated by Manual Metal Arc (MMA) and Metal Active Gas (MAG) processes. The selected samplers were the ones available in Spain when the study began: IOM, PGP-GSP 3.5 (GSP) and Button. Sampling was carried out in a welding training center that provided a homogeneous workplace environment. The static sampling assembly used allowed the placement of 12 samplers and 2 cascade impactors simultaneously. 183 samples were collected throughout 2009 and 2010. The range of welding fumes' mass concentrations was from 2 mg m(-3) to 5 mg m(-3). The pooled variation coefficients for the three inhalable samplers were less than or equal to 3.0%. Welding particle size distribution was characterized by a bimodal log-normal distribution, with MMADs of 0.7 MUm and 8.2 MUm. For these welding aerosols, the Button and the GSP samplers showed a similar performance (P = 0.598). The mean mass concentration ratio was 1.00 +/- 0.01. The IOM sampler showed a different performance (P < 0.001). The mean mass concentration ratios were 0.90 +/- 0.01 for Button/IOM and 0.92 +/- 0.02 for GSP/IOM. This information is useful to consider the measurements accomplished by the IOM, GSP or Button samplers together, in order to assess the exposure at workplaces over time or to study exposure levels in a specific industrial activity, as welding operations. PMID- 22037835 TI - [Orbital pain from a cranio-maxillofacial surgery perspective]. AB - Orbital pain can be provoked by diseases of the orbital skeleton as well as the maxillary sinus. Infections of the maxillary sinus caused by dental infections (e.g. periodontitis) or root canal treatment represent the majority of these cases followed by injuries of the orbital skeleton. An appropriate medical history usually provides indications for the further diagnostic procedure. In rare cases diseases of the facial skeleton as well as Wegener's granulomatosis can also cause orbital pain. In contrast temporomandibular disorders (TMD) may cause motility disorders and alterations in binocular vision but are not responsible for orbital pain. PMID- 22037836 TI - [Two-wall decompression without resection of the medial wall. Effect on squint angle]. AB - BACKGROUND: Postoperative new onset diplopia can be a disadvantage for surgical orbital decompression in patients with exophthalmos in thyroid eye disease. The various modifications of decompression (number and combination of walls) differ in their influence on the postoperative squint angle. We report on postoperative diplopia in a modified 2 wall decompression strategy (lateral wall and floor). METHODS: This study was a retrospective analysis of 36 consecutive 2-wall decompressions performed between 2006-2010 in 24 patients with 6 months of stable exophthalmos in thyroid eye disease after medical therapy and radiotherapy. The preoperative and postoperative squint angle in prism cover test (PCT), motility, induction of diplopia, reduction of exophthalmos, visual acuity and complications were evaluated. RESULTS: In all 36 decompressions the postoperative squint angle was equal to or less than before surgery. In 8 eyes additional squint surgery was performed. The mean reduction in exopthalmos was 4.3 mm. CONCLUSIONS: An adverse effect of decompression on the postoperative squint angle was not evident in this study. New induction of diplopia was not observed at all. One possible explanation is the preservation of the medial wall. PMID- 22037837 TI - [Arguments for prophylactic therapy of ocular hypertension]. AB - Increased intraocular pressure is currently the only manipulable risk factor for glaucoma. In ocular hypertension the intraocular pressure is increased but the optic nerve head and visual field are thought to show no damage. Classification into glaucoma by means of the optic nerve head is often possible only over a period of time because there is a large overlap between the already pathological and still normal findings. In the Ocular Hypertension Treatment Study (OHTS) the effectiveness of prophylactic treatment was demonstrated. In the OHTS and the European Glaucoma Prevention Study (EGPS) risk factors have been identified, such as increased intraocular pressure, size of the excavation of the optic nerve head, decreased central corneal thickness, increased pattern standard deviation in the visual field and age. Before treatment of ocular hypertension is initiated these risk factors and the patient's personal situation should be considered. The higher the intraocular pressure, the smaller the central corneal thickness and the larger the excavation of the optic nerve and the younger the patient, the earlier treatment should be started. PMID- 22037838 TI - [Preparation of the amniotic membrane with the waterjet]. AB - BACKGROUND: Ex vivo culturing of limbal stem cells on human amniotic membranes can be accelerated if all amniotic epithelial cells have been removed beforehand. A common application of acellular amniotic membranes is their use in cultivating autologous oral mucosal epithelial cells for transplantation in cases of bilateral stem cell insufficiency. Amniotic epithelial cells can be eliminated with enzymatic-chemical or mechanical methods or with a combination of both. MATERIAL AND METHODS: The efficacy of a waterjet cutter to eliminate amniotic epithelial cells from the amniotic membrane was investigated. Deep frozen placentas from healthy mothers were defrosted and a well-defined surface of the amniotic membrane (d = 15 mm) was treated with the waterjet in a standardized way. The waterjet used two different nozzles (pin-point and narrow stream nozzles). The applied system pressures with the pin-point stream nozzle (aperture 120 MUm) were 30, 40 and 50 bar and the narrow stream nozzle was operated with pressures of 70, 80 and 90 bar on the amniotic membrane. A total number of 42 tissue samples were examined with an optical microscope using native trypan blue staining. For each type of nozzle and each application pressure two amnion samples were examined with a scanning electron microscope to analyze the efficacy of the mechanical epithelial cell elimination from the amniotic membrane. After medical imaging and histopathological examination the efficacy was graded using the following scale: 0 = no amniotic epithelial cells, 1 = no cells, low amounts of cell debris, 2 = single amniotic epithelial cells, large amounts of cell debris, 3 = loose cell layer, 4 = continuous sheet of epithelial cells. RESULTS: To eliminate epithelial cells from the surface of the amniotic membrane with the waterjet pinpoint stream nozzle (aperture: 120 MUm) an application pressure of 30 50 bar was needed. The use of the narrow stream nozzle required a pressure of 70 90 bar. CONCLUSIONS: The preparation of amniotic membranes with the waterjet represents a precise option to mechanically eliminate amniotic epithelial cells from the amniotic membrane. The use of a waterjet cutter as an exclusively mechanical method without enzymatic-chemical substances may be a benefit, as cytotoxic effects on culturing limbal stem cells caused by chemical substances are not present. PMID- 22037839 TI - Hypothyroid states mitigate the diabetes-induced reduction of calbindin D-28k, calretinin, and parvalbumin immunoreactivity in type 2 diabetic rats. AB - In this study, we investigated the differences in calbindin D-28k (CB), calretinin, (CR) and parvalbumin (PV) immunoreactivity in the hippocampus of Zucker diabetic fatty (ZDF) rats and Zucker lean control (ZLC) rats. In addition, we observed the effects of hypothyroidism on the levels of immunoreactivity of these proteins in ZDF rats. For this study, 7-week-old ZDF rats were used, and methimazole treatment was continued for 5 weeks to induce hypothyroidism. The animals were sacrificed at 12 weeks of age. ZDF rats showed increased blood glucose levels compared to those in ZLC rats. Methimazole intervention significantly reduced total and free T3 levels, and it ameliorated the increase of blood glucose levels in ZDF rats. In ZLC rats, CB, CR, and PV immunoreactivity was detected in regions of the hippocampus proper. In vehicle-treated ZDF rats, CB, CR, and PV immunoreactivity was significantly decreased in the hippocampus. However, in the methimazole-treated rats, CB, CR, and PV immunoreactivity was significantly increased compared to that in the vehicle-treated rats. These results suggest that hypothyroidism ameliorated the diabetes-induced reduction of CB, CR, and PV immunoreactivity in the hippocampus. PMID- 22037840 TI - Increased immunoreactivities of cleaved alphaII-spectrin and cleaved caspase-3 in the aged dog spinal cord. AB - The activation of caspase-3 is considered to be a reliable marker for apoptotic cell death, and a 120-kDa fragment of alphaII-spectrin is generated by caspase-3 mediated cleavage of this structural protein. In the present study, we compared cleaved alphaII-spectrin (120-kDa) and cleaved caspase-3-immunoreactive cells and their protein levels in the cervical (C5-C6) and lumbar (L3-L4) levels of the spinal cord in adult (1-2 year-old) and aged (10-12 year-old) dogs (German shepherds). Weak cleaved alphaII-spectrin and cleaved caspase-3 immunoreactivity was found in neurons of the adult group; however, their immunoreactivity was distinctively increased in the neuronal cytoplasm in the aged group compared to those in the adult group, although the distribution pattern of their neurons was similar between the adult and age group. In addition, cleaved alphaII-spectrin and cleaved caspase-3 levels in the aged spinal cord were markedly increased compared to those in the adult group. These findings suggest that the increases of cleaved alphaII-spectrin and cleaved caspase-3 immunoreactivity may be related to aging of the spinal cord in dogs. PMID- 22037841 TI - Effects of sensitive to apoptosis gene protein on cell proliferation, neuroblast differentiation, and oxidative stress in the mouse dentate gyrus. AB - Sensitive to apoptosis gene (SAG) protein is a redox-inducible protein that protects cells against apoptosis induced by redox agents. In this study, we observed effects of SAG on cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus (DG) using Ki67 and doublecortin (DCX), respectively. For easy penetration into neurons, Tat-SAG expression vector was constructed by ligation with SAG and expression vector, Tat, in-frame with six histidine open-reading frames to generate the expression vector, and cloned into E. coli DH5alpha cells. One or 5 mg/kg Tat-SAG fusion protein (Tat-SAG) was intraperitoneally administered to mice once a day for 3 weeks. The administration of Tat-SAG significantly increased the number of 5-bromodeoxyuridine positive cells, Ki67 positive cells and DCX immunoreactive neuroblast in the mouse DG: Especially, in the 5 mg/kg Tat-SAG-treated mice, DCX positive neuroblasts showed a well-developed arborization of tertiary dendrites in the DG. On the other hand, we examined that the administration of Tat-SAG significantly reduced the DNA damage and lipid peroxidation judging from 8-hydroxy-2'-deoxyguanosine and 4 hydroxynonenal immunohistochemistry: The decrease was much more distinct in the 5 mg/kg Tat-SAG-treated mice than 1 mg/kg Tat-SAG-treated mice. This result suggests that SAG significantly increases cell proliferation, neuroblast differentiation and oxidative stress in normal states. PMID- 22037842 TI - Phospho-Rb mediating cell cycle reentry induces early apoptosis following oxygen glucose deprivation in rat cortical neurons. AB - The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen-glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 MUM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint. PMID- 22037844 TI - Trends over time in the size and quality of randomised controlled trials of interventions for chronic low-back pain. AB - PURPOSE: Previous reviews of randomised controlled trials (RCTs) for low-back pain (LBP) have failed to identify any positive trend in study quality with more recent years of publication. This study aimed to identify and describe trends over time in the study design characteristics and risk of bias in chronic LBP trials performed over the past 30 years. METHODS: One fifty-seven randomised trials of interventions for chronic LBP were extracted from recently published systematic reviews. The reviews included RCTs on physical and rehabilitation interventions, injection therapy and denervation procedures, complementary and alternative therapies and pharmacological interventions for chronic LBP. Study level data were extracted and analysed for trends associated with year of publication. RESULTS: Overall, the mean sample size in the RCTs was 141 (median 70; range 17-3093). There was a slight increase in the median number of risk of bias criteria fulfilled from trials published prior to 1995 to those published after 1996. The analysis showed that in more recent years RCTs of medical interventions were more likely to be successfully blinded than RCTs of non medical interventions. CONCLUSIONS: The continuing uncertainty regarding the efficacy of many interventions for chronic LBP again stresses the need for large RCTs with low risk of bias. Further research is needed into specific risks of bias within the RCTs for chronic LBP and the effect they have on the plausibility of the results. PMID- 22037846 TI - Psychological essentialist reasoning and perspective taking during reading: a donkey is not a zebra, but a plate can be a clock. AB - In an eyetracking study, we examined whether readers use psychological essentialist reasoning and perspective taking online. Stories were presented in which an animal or an artifact was transformed into another animal (e.g., a donkey into a zebra) or artifact (e.g., a plate into a clock). According to psychological essentialism, the essence of the animal did not change in these stories, while the transformed artifact would be thought to have changed categories. We found evidence that readers use this kind of reasoning online: When reference was made to the transformed animal, the nontransformed term ("donkey") was preferred, but the opposite held for the transformed artifact ("clock" was read faster than "plate"). The immediacy of the effect suggests that this kind of reasoning is employed automatically. Perspective taking was examined within the same stories by the introduction of a novel story character. This character, who was naive about the transformation, commented on the transformed animal or artifact. If the reader were to take this character's perspective immediately and exclusively for reference solving, then only the transformed term ("zebra" or "clock") would be felicitous. However, the results suggested that while this character's perspective could be taken into account, it seems difficult to completely discard one's own perspective at the same time. PMID- 22037845 TI - Epidemiological characteristics of adult SCIWORA in Tianjin, China: a preliminary study. AB - INTRODUCTION: The epidemiology of spinal cord injury without radiographic abnormality (SCIWORA) is less frequently reported in adults as compared with children. The annual incidence of SCIWORA was approximately 5.74% per million in Tianjin from 2004 to 2008. Importantly, the epidemiological characteristics of adult SCIWORA may be different from that in children. The aim of this study was to evaluate the radiological-clinical data of patients with adult SCIWORA, and to relatively analyze the epidemiological features. MATERIALS AND METHODS: Inpatients with cervical SCIWORA who were 16 and above in Tianjin were admitted in municipal hospitals in Tianjin from 2004 to 2008; all the patients received MRI scanning in sagittal and axial views. Epidemiological characteristics, such as injury origin, injury level or severity, neurological scale and MRI feature were acquired. RESULTS: In total, 203 patients were enrolled. The average age among the adult groups was 55.9 years (men 55.8 years, women 53.6 years). SCIWORA occurred more commonly in adults in the 46-60 age group, and falls were the leading cause of injury (52.2%), followed by vehicular injury (28.6%). The most predominantly affected level was C4/5 (48.7%), followed by C5/6 (30.5%) and C3/4 (12.8%), respectively. The occurrence of central cord syndrome (50.2%) with posterior longitudinal ligament tear (43.8%) was relatively higher than other injury patterns. CONCLUSION: It is clear that adult cervical SCIWORA is different from that in the pediatric group. Our study highlights the epidemiological properties of adult SCIWORA in Tianjin, China. Differing from other reports, particularly epidemiology study, we represent the first report regarding adult SCIWORA from China. As the geriatric population increases, it is very important to set up an individualized evaluation system based on a nationally scaled epidemiological database. The results from our study will be useful in assisting in the creation of such a database. PMID- 22037847 TI - A novel metabolite of antituberculosis therapy demonstrates host activation of isoniazid and formation of the isoniazid-NAD+ adduct. AB - One of the most effective and widely used antituberculosis (anti-TB) drugs is isoniazid (INH), a prodrug activated via oxidation that forms an adduct with NAD(+) to inhibit NADH-dependent targets of Mycobacterium tuberculosis, such as enoyl-acyl carrier protein reductase (InhA). The metabolic by-products and potentially toxic intermediates resulting from INH therapy have been identified through a large body of work. However, an INH-NAD adduct or structures related to this adduct have not been identified in specimens from human TB patients or animal models of TB. Analyses by mass spectrometry of urine collected from TB patients in a study conducted by the NIAID-funded Tuberculosis Research Unit identified 4-isonicotinoylnicotinamide (C(12)H(9)N(3)O(2)) as a novel metabolite of INH therapy. This compound was formed by M. tuberculosis strains in a KatG dependent manner but could also be produced by mice treated with INH independent of an M. tuberculosis infection. Thus, the 4-isonicotinoylnicotinamide observed in human urine samples is likely derived from the degradation of oxidized INH-NAD adducts and provides direct evidence of host INH activation. PMID- 22037848 TI - F18, a novel small-molecule nonnucleoside reverse transcriptase inhibitor, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis. AB - Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are one of the key components of antiretroviral therapy drug regimen against human immunodeficiency virus type 1 (HIV-1) replication. We previously described a newly synthesized small molecule, 10-chloromethyl-11-demethyl-12-oxo-calanolide A (F18), a (+) calanolide A analog, as a novel anti-HIV-1 NNRTI (H. Xue et al., J. Med. Chem. 53:1397-1401, 2010). Here, we further investigated its antiviral range, drug resistance profile, and underlying mechanism of action. F18 consistently displayed potent activity against primary HIV-1 isolates, including various subtypes of group M, circulating recombinant form (CRF) 01_AE, and laboratory adapted drug-resistant viruses. Moreover, F18 displayed distinct profiles against 17 NNRTI-resistant pseudoviruses, with an excellent potency especially against one of the most prevalent strains with the Y181C mutation (50% effective concentration, 1.0 nM), which was in stark contrast to the extensively used NNRTIs nevirapine and efavirenz. Moreover, we induced F18-resistant viruses by in vitro serial passages and found that the mutation L100I appeared to be the dominant contributor to F18 resistance, further suggesting a binding motif different from that of nevirapine and efavirenz. F18 was nonantagonistic when used in combination with other antiretrovirals against both wild-type and drug resistant viruses in infected peripheral blood mononuclear cells. Interestingly, F18 displayed a highly synergistic antiviral effect with nevirapine against nevirapine-resistant virus (Y181C). Furthermore, in silico docking analysis suggested that F18 may bind to the HIV-1 reverse transcriptase differently from other NNRTIs. This study presents F18 as a new potential drug for clinical use and also presents a new mechanism-based design for future NNRTI. PMID- 22037849 TI - An enlarged, adaptable active site in CYP164 family P450 enzymes, the sole P450 in Mycobacterium leprae. AB - CYP164 family P450 enzymes are found in only a subset of mycobacteria and include CYP164A1, which is the sole P450 found in Mycobacterium leprae, the causative agent of leprosy. This has previously led to interest in this enzyme as a potential drug target. Here we describe the first crystal structure of a CYP164 enzyme, CYP164A2 from Mycobacterium smegmatis. CYP164A2 has a distinctive, enlarged hydrophobic active site that extends above the porphyrin ring toward the access channels. Unusually, we find that CYP164A2 can simultaneously bind two econazole molecules in different regions of the enlarged active site and is accompanied by the rearrangement and ordering of the BC loop. The primary location is through a classic interaction of the azole group with the porphyrin iron. The second econazole molecule is bound to a unique site and is linked to a tetracoordinated metal ion complexed to one of the heme carboxylates and to the side chains of His 105 and His 364. All of these features are preserved in the closely homologous M. leprae CYP164A1. The computational docking of azole compounds to a homology model of CYP164A1 suggests that these compounds will form effective inhibitors and is supported by the correlation of parallel docking with experimental binding studies of CYP164A2. The binding of econazole to CYP164A2 occurs primarily through the high-spin "open" conformation of the enzyme (K(d) [dissociation constant] of 0.1 MUM), with binding to the low-spin "closed" form being significantly hindered (K(d) of 338 MUM). These studies support previous suggestions that azole derivatives may provide an effective strategy to improve the treatment of leprosy. PMID- 22037850 TI - Molecular dynamics approaches estimate the binding energy of HIV-1 integrase inhibitors and correlate with in vitro activity. AB - The design of novel integrase (IN) inhibitors has been aided by recent crystal structures revealing the binding mode of these compounds with a full-length prototype foamy virus (PFV) IN and synthetic viral DNA ends. Earlier docking studies relied on incomplete structures and did not include the contribution of the viral DNA to inhibitor binding. Using the structure of PFV IN as the starting point, we generated a model of the corresponding HIV-1 complex and developed a molecular dynamics (MD)-based approach that correlates with the in vitro activities of novel compounds. Four well-characterized compounds (raltegravir, elvitegravir, MK-0536, and dolutegravir) were used as a training set, and the data for their in vitro activity against the Y143R, N155H, and G140S/Q148H mutants were used in addition to the wild-type (WT) IN data. Three additional compounds were docked into the IN-DNA complex model and subjected to MD simulations. All three gave interaction potentials within 1 standard deviation of values estimated from the training set, and the most active compound was identified. Additional MD analysis of the raltegravir- and dolutegravir-bound complexes gave internal and interaction energy values that closely match the experimental binding energy of a compound related to raltegravir that has similar activity. These approaches can be used to gain a deeper understanding of the interactions of the inhibitors with the HIV-1 intasome and to identify promising scaffolds for novel integrase inhibitors, in particular, compounds that retain activity against a range of drug-resistant mutants, making it possible to streamline synthesis and testing. PMID- 22037851 TI - In vitro and in vivo trypanocidal synergistic activity of N-butyl-1-(4 dimethylamino)phenyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxamide associated with benznidazole. AB - American trypanosomiasis, or Chagas' disease, is caused by Trypanosoma cruzi and affects around 15 million people throughout the American continent. The available treatment is based on two nitroheterocyclic drugs, nifurtimox and benznidazole, both only partially effective and toxic. In this context, new drugs must be found. In our previous work, the tetrahydro-beta-carboline compound N-butyl-1-(4 dimethylamino)phenyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxamide, named C4, showed a potent in vitro trypanocidal effect. The goal of this study was to evaluate the in vitro and in vivo trypanocidal effects of the compound C4 associated with other drugs (benznidazole, ketoconazole, and amphotericin B). For this, we used the checkerboard technique to analyze the effect of combinations of C4 reference drugs. C4 was assayed in a murine model alone as well as in association with benznidazole. We also evaluated the parasitemia, mortality, weight, and presence of amastigote nests in cardiac tissue. A synergic effect of C4 plus benznidazole against epimastigote and trypomastigote forms was observed in vitro, and in the murine model, we observed a substantial reduction in parasitemia levels and lowered mortality rates. These findings encourage supplementary investigations of carboline compounds as potential new trypanocidal drugs. PMID- 22037852 TI - Activation of benznidazole by trypanosomal type I nitroreductases results in glyoxal formation. AB - Benznidazole, a 2-nitroimidazole, is the front-line treatment used against American trypanosomiasis, a parasitic infection caused by Trypanosoma cruzi. Despite nearly 40 years of use, the trypanocidal activity of this prodrug is not fully understood. It has been proposed that benznidazole activation leads to the formation of reductive metabolites that can cause a series of deleterious effects, including DNA damage and thiol depletion. Here, we show that the key step in benznidazole activation involves an NADH-dependent trypanosomal type I nitroreductase. This catalyzes an oxygen-insensitive reaction with the interaction of enzyme, reductant, and prodrug occurring through a ping-pong mechanism. Liquid chromatography/mass spectrometry (LC/MS) analysis of the resultant metabolites identified 4,5-dihydro-4,5-dihydroxyimidazole as the major product of a reductive pathway proceeding through hydroxylamine and hydroxy intermediates. The breakdown of this product released the reactive dialdehyde glyoxal, which, in the presence of guanosine, generated guanosine-glyoxal adducts. These experiments indicate that the reduction of benznidazole by type I nitroreductase activity leads to the formation of highly reactive metabolites and that the expression of this enzyme is key to the trypanocidal properties displayed by the prodrug. PMID- 22037853 TI - Pharmacokinetic-pharmacodynamic model for gentamicin and its adaptive resistance with predictions of dosing schedules in newborn infants. AB - Gentamicin is commonly used in the management of neonatal infections. Development of adaptive resistance is typical for aminoglycosides and reduces the antibacterial effect. There is, however, a lack of understanding of how this phenomenon influences the effect of different dosing schedules. The aim was to develop a pharmacokinetic-pharmacodynamic (PKPD) model that describes the time course of the bactericidal activity of gentamicin and its adaptive resistance and to investigate different dosing schedules in preterm and term newborn infants based on the developed model. In vitro time-kill curve experiments were conducted on a strain of Escherichia coli (MIC of 2 mg/liter). The gentamicin exposure was either constant (0.125 to 16 mg/liter) or dynamic (simulated concentration-time profiles in a kinetic system with peak concentrations of 2.0, 3.9, 7.8, and 16 mg/liter given as single doses or as repeated doses every 6, 12, or 24 h). Semimechanistic PKPD models were fitted to the bacterial counts in the NONMEM (nonlinear mixed effects modeling) program. A model with compartments for growing and resting bacteria, with a function allowing the maximal bacterial killing of gentamicin to reduce with exposure, characterized both the fast bactericidal effect and the adaptive resistance. Despite a lower peak concentration, preterm neonates were predicted to have a higher bacterial killing effect than term neonates for the same per-kg dose because of gentamicin's longer half-life. The model supported an extended dosing interval of gentamicin in preterm neonates, and for all neonates, dosing intervals of 36 to 48 h were as effective as a 24-h dosing interval for the same total dose. PMID- 22037854 TI - Antibiotic modulation of the plasminogen binding ability of viridans group streptococci. AB - The ability of viridans group streptococci to bind human plasminogen and its subsequent activation into plasmin may contribute to the pathogenesis of infective endocarditis (IE) by leading to a decreased stability of the streptococcal vegetation and facilitating dehiscence of emboli. At levels greater than or equal to their MICs, penicillin, vancomycin, and linezolid are efficacious in the treatment of streptococcal endocarditis. However, at sub-MICs, antibiotics can modulate the expression of bacterial genes, including virulence associated genes, which can have counterproductive effects on the treatment of endocarditis. The effects of 1/8* and 1/4* MICs of penicillin, vancomycin, and linezolid on the plasminogen binding ability of IE isolates Streptococcus mitis 881/956, Streptococcus oralis 12601, and Streptococcus sanguinis 12403 were assessed phenotypically and the expression of plasminogen receptors alpha-enolase and glyceraldehyde 3-phosphate dehydrogenase of S. oralis 12601 when exposed to 1/4* MIC of penicillin, was analyzed through quantitative reverse transcription (qRT)-PCR. The plasminogen binding ability of S. mitis 881/956 and S. sanguinis 12403 remained unaffected by exposure to sub-MICs of all of the antibiotics tested, while that of S. oralis 12601 was significantly enhanced by all of the antibiotics tested at sub-MICs. qRT-PCR analysis of S. oralis 12601 demonstrated an upregulation of the eno and gapdh genes, indicating an overexpression of plasminogen receptors. These findings suggest that for some endocarditis isolates, the effect of antibiotic sub-MICs, in addition to a reduced antibacterial effect, may influence the clinical response to nonsurgical therapy. It remains difficult to accurately predict isolate responses to sub-MIC antimicrobials since there appears to be interspecies variation. PMID- 22037855 TI - Prevalence of and risk factors for syphilis in Brazilian armed forces conscripts. AB - OBJECTIVE: The aim of this study was to describe the prevalence of syphilis by geographical region and the frequency of behaviours and symptoms related to sexually transmitted diseases (STD). METHODS: A cross-sectional study was performed with Brazilian conscripts in 2007. They answered a self-administered questionnaire on demographic issues, sexual practices, condom use and STD symptoms. They had a blood sample collected for a syphilis test. RESULTS: A total of 35 460 conscripts answered the questionnaire and 75.5% reported previous sexual intercourse. Overall syphilis prevalence was 0.53% (95% CI 0.45% to 0.61%). By geographical region: northern (0.85%), northeast (0.82%), midwest (0.49%), southeast (0.34%) and southern region (0.26%). The final logistic regression model showed an association among having had syphilis and being 17 years old (OR 1.3; 95% CI 1.05 to 1.73), having up to 8 years of schooling (OR 1.5; 95% CI 1.03 to 2.22), living in the northern/northeast region (OR 1.2; 95% CI 1.04 to 1.36), being men who have sex with men (OR 4.5; 95% CI 2.59 to 7.81), reporting a previous history of STD (OR 2.7; 95% CI 1.03 to 6.99) and genital ulcers (OR 2.6; 95% CI 1.59 to 4.26). CONCLUSIONS: Addressing young people at the time of military enlistment may be a good time to consider new strategies for accessing and counselling this population, thus allowing the implementation of a more appropriate healthcare policy. PMID- 22037856 TI - Clinicohematological profile and platelet trends in children with dengue during 2010 epidemic in north India. AB - OBJECTIVE: To study the clinicohematological profile and the platelet trends in children presenting with dengue infection during the 2010 dengue epidemic in north India and to compare the it with previous epidemics. METHODS: This retrospective study was carried out in a tertiary care hospital of North India. Of the 219 children admitted from August 2010 through November 2010 with suspected dengue infection, 135 were IgM positive and were included in the final analysis. RESULTS: These children were further categorized as dengue fever (8%), dengue hemorrhagic fever (51%) and dengue shock syndrome (42%). The mean age (+/- SD) of children were 8.3 +/- 3.5 y with male: female ratio 1.32. Mean duration of fever (+/-SD) was 6.3 d +/- 3.7 d. The clinical features included fever (100%), headache (63%), abdominal pain (71%), petechia (35.5%), rash (26.6%) and bleeding manifestations (48.8%). On examination, Hess test (33.3%), signs of fluid retention (23%), pallor (13.3%),signs of circulatory failure (43%), hepatomegaly (31.1%) and splenomegaly (27%) were positive. Laboratory investigations revealed mean (+/-SD) hemoglobin 11.5 g/dl (+/-1.7), hematocrit 36.1(+/-5.5), leucocyte count 7,551/mm(3) and platelet count 38,800 mm(3) on day of admission. A total of 92.6% of children had thrombocytopenia and 19.2% had abnormal leucocyte count. Deranged liver function tests were observed in 48 children. The mean (+/-SD) of hospitalization and platelet recovery were 4.2 +/- 2.3 d and 3.6 +/- 1.3 d respectively and did not vary according to disease category (P > 0.05). Bleeding manifestations were not related to platelet count (P > 0.05). There was no statistical difference in the demographic, clinical or laboratory observations according to disease category (P > 0.05). A total of 24 children had evidence of other co-infections and four had atypical complications. Dengue 2 virus was the strain reported in most of the cases. CONCLUSIONS: This study showed shift to higher age of presentation, more number of dengue hemorrhagic fever and associated co-infections in children. The complications and mortality was low and platelet recovery time was not influenced by disease category. PMID- 22037857 TI - Incidence of Vesicobullous and Erosive Disorders of Neonates: Where and How Much to Worry? AB - OBJECTIVE: To analyse the incidence of dermatoses in neonates, stress the importance of simple noninvasive diagnostic procedures with perspective to actual need of active intervention. METHODS: Forty four neonates with vesicobullous lesions in Departments of Dermatology and Pediatrics were evaluated with respect to diagnosis, required treatments and follow ups. RESULTS: Of the total 44 neonates, 29 were boys and 15 girls. Low birth weight (weight at birth less than 2,500 g as per WHO criteria) was seen in 19 neonates. Of the infectious dermatoses, most common were pyodermas. Four cases (9%) were diagnosed to be of staphylococcal pyoderma and impetigo and two cases each of Group A Streptococcal impetigo and neonatal tinea faciei (4.5% each), one case each of neonatal candidiasis, neonatal varicella/chickenpox and scabies (2.3% each) were seen. Of the transient skin lesions, erythema toxicum neonatorum was commonest of all, being seen in 18 neonates (41%), followed by four cases (9%) of miliaria crystallina, three cases of neonatal acne (6.8%) and two cases of sucking blisters (4.5%) and one case each of transient neonatal pustular melanosis, epidermolysis bullosa simplex, incontinentia pigmentii, eosinophilic pustular folliculitis, pemphigus vulgaris and neonatal herpes simplex (2.3% each) were enrolled in this study (Fig. 1). Fig. 1 Piechart showing percentage and number of neonates with different diagnostic profiles in the study CONCLUSIONS: Certain specific considerations have to be born in mind while evaluating and managing neonatal dermatoses. Care has to be instituted to identify accurately infectious diseases and distinguish them from benign transient neonatal dermatoses. Some disorders first manifesting during the neonatal period may also represent harbingers of potential problems during adulthood. Finally, treatment modalities are instituted taking in account the actual diagnosis and judging if the treatment really is required or not. PMID- 22037858 TI - Current concepts in growth hormone therapy. PMID- 22037859 TI - Growth hormone deficiency: optimizing therapy and new issues. AB - Growth Hormone Deficiency (GHD) with low circulating IGF1 requires replacement therapy. Paradoxically, it remains a controversial issue in a large part of patients, those considered as having isolated GHD of the idiopathic milder form. Challenges remain in this area in spite of intensive and sometimes controversial studies. This is true for the diagnosis of the milder forms (also called partial GHD), for the assessment of the growth response and the evaluation of final height benefit. In addition the cost-benefit issue should not be ignored. Therefore, the author tried to review data relevant to the evaluation of GH secretion which even now remains largely arbitrary. The growth response, which is the primary therapeutic goal in these children should also be carefully discussed as reported in recent papers. Focusing on individual responses should help adjusting individual dosage within the standard recommended doses, but one should also remember that there are no long term safety data for non conventional high rhGH doses. More studies are needed. Response to treatment during the first year may in the future help select the patients who are prone to the benefit of long term rhGH therapy. Basic rules for indication and progression of treatment are proposed in children with various forms of GHD. It is also remarkable that the present safety data are all coming from several post-marketing studies. This means that long term independent studies are now required as recombinant growth hormone remains the most appropriate and efficient therapy when permanent GH deficiency is fully documented. PMID- 22037860 TI - Frank-Ter Haar syndrome in a newborn. AB - Frank-Ter Haar syndrome is an unusual type of skeletal dysplasia with megalocornea and developmental delay. It is usually transmitted as autosomal recessive disorder. Only a few cases have been reported in the literature and none from India. The authors report a case with other unusual features and a short review of the condition. PMID- 22037861 TI - Change in drinking water quality from source to point-of-use and storage: a case study from Guwahati, India. AB - To ascertain the quality of drinking water being supplied and maintained at Guwahati, the study was conducted on the status of water supply in city through surveillance of drinking water quality for consecutive 7 days at various treatment stages, distribution network and consumer ends. The performance of five water treatment plants (WTPs), viz. Panbazar WTP, Satpukhuri WTP, Kamakhya WTP, PHED WTP and Hegrabari WTP were assessed for summer, piost-post-monsoon and winter seasons. No significant change in raw water quality was observed on day-to day basis. Residual chlorine was found in the range of nil to 0.2 mg/L in the treated water. During post-monsoon, winter, and summer seasons the thermotolerent TC and FC counts ranged between Nil to 168 CFU/100 ml and Nil to 84 CFU/100 ml; Nil to 3356 CFU/100 ml and Nil to 152 CFU/100 ml; and Nil to 960 CFU/100 ml and Nil to 108 CFU/100 ml respectively. There was variation in bacterial counts among the different service reservoirs and consumer ends, which may be attributed to the general management practices for maintenance of service reservoirs and the possibility of enroute contamination. Evaluation of the raw water quality indicate that the water is suitable for drinking after conventional treatment followed by disinfection. The finished water quality meets the level of standards described as per Bureau of Indian Standard specifications (BIS:10500 1991) for potability in terms of its physico-chemical characteristics. PMID- 22037862 TI - Microbial preference for different size classes of organic carbon: a study from Antarctic snow. AB - Significance of carbon cycling in polar ecosystems is well recognized. Yet, bacteria in surface snow have received less attention in terms of their potential in carbon cycling. Here, we present results on carbon utilization by bacterial communities in three surface snow samples from Antarctica collected along a coastal to inland transect. Microcosm studies were conducted over 8 days at 5 +/- 1 degrees C to study carbon metabolism in different combinations of added low molecular weight (LMW (glucose, <1 kDa)) and high molecular weight (HMW (starch, >1 kDa)) substrates (final 20 ppm). The total organic carbon (TOC) in the snow samples decreased with time at rates ranging from non-detectable to 1.4 ppm day( 1) with rates highest in snow samples from inland region. In addition, carbon utilization studies were also carried out with bacterial isolates LH1, LH2, and LH4 belonging to the genus Cellulosimicrobium, Bacillus, and Ralstonia, respectively, isolated from the snow samples. Studies with strain LH2 in different amendments of glucose and starch showed that TOC decreased with time in all amendments at a rate of 0.9-1.5 ppm day(-1) with highest rates of 1.4-1.5 ppm day(-1) in amendments containing a higher proportion of starch. The bacterial isolates were also studied to determine their ability to utilize other LMW and HMW compounds. They utilized diverse substrates like carbohydrates, amino acids, amines, amides, complex polymers, etc., of molecular mass <100 Da, 100-500 Da, >500 Da-1 kDa, and >1 kDa preferring (up to 31 times) substrates with mass of >1 kDa than <1 kDa. The ability of bacteria in snow to utilize diverse LMW and HMW substrates indicates that they could be important in the uptake of similar compounds in snow and therefore potentially govern snow chemistry. PMID- 22037863 TI - An observational study of the carrying capacity of suspended sediment during a storm event. AB - We measured the in situ suspended sediment concentration (SSC) and hydrodynamics (waves, currents, and sea level) concurrently during a storm event using self recording instruments at offshore of the Shandong Peninsula in the Yellow Sea. We analyzed the temporal variation in suspended sediment carrying capacity and its correlation with wave, current, and water-level conditions. There was about 40% increase in SSC during the storm event. A 3-4-h lag was observed between the peak of wave height and SSC. The SSC increased in a fluctuating pattern up to the peak then decreased rapidly. This process was positively correlated with wave height and duration. The maximum SSC was 524.3 mg/l, which is about 10 times of that under normal weather conditions. This peak was observed after of a series of 1.8 m waves. The increased suspended sediments were the fine particles resuspended by the storm waves from seabed near the observation spot and transported by northward ebb currents from Shidao Bay. PMID- 22037864 TI - Development of a mass-producible on-chip plasmonic nanohole array biosensor. AB - We have developed a polymer film based plasmonic device whose optical properties are tuned for measuring biological samples. The device has a circular nanohole array structure fabricated with a nanoimprint technique using a UV curable polymer, and then gold thin film is deposited by electron beam deposition. Therefore, the device is mass-producible, which is also very important for bioaffinity sensors. First the gold film thickness and hole depth were optimized to obtain the maximum dip shift for the reflection spectra. The dip shift is equivalent to the sensitivity to refractive index changes at the plasmonic device surface. We also calculated the variation in reflection spectra by changing the above conditions using the finite-difference time domain method, and we obtained agreement between the theoretical and experimental curves. The nanohole periodicity was adjusted from 400 to 900 nm to make it possible to perform measurements in the visible wavelength region to measure the aqueous samples with less optical absorption. The tuned bottom filled gold nanohole array was incorporated in a microfluidic device covered with a PDMS based microchannel that was 2 mm wide and 20 MUm deep. As a proof of concept, the device was used to detect TNF-alpha by employing a direct immunochemical reaction on the plasmonic array, and a detection limit of 21 ng mL(-1) was obtained by amplification with colloidal gold labeling instead of enzymatic amplification. PMID- 22037865 TI - Effect of calorie restriction and refeeding on skin wound healing in the rat. AB - Calorie restriction (CR) is a reliable anti-aging intervention that attenuates the onset of a number of age-related diseases, reduces oxidative damage, and maintains function during aging. In the current study, we assessed the effects of CR and other feeding regimens on wound healing in 7-month-old Fischer-344 rats from a larger cohort of rats that had been fed either ad libitum (AL) or 40% calorie restricted based on AL consumption. Rats were assigned to one of three diet groups that received three skin punch wounds along the dorsal interscapular region (12-mm diameter near the front limbs) of the back as follows: (1) CR (n = 8) were wounded and maintained on CR until they healed, (2) AL (n = 5) were wounded and maintained on AL until wound closure was completed, and (3) CR rats were refed (RF, n = 9) AL for 48 h prior to wounding and maintained on AL until they healed. We observed that young rats on CR healed more slowly while CR rats refed for 48 h prior to wounding healed as fast as AL fed rats, similar to a study reported in aged CR and RF mice (Reed et al. 1996). Our data suggest that CR subjects, regardless of age, fail to heal well and that provision of increased nutrition to CR subjects prior to wounding enhances the healing process. PMID- 22037867 TI - Short-term nanostructural effects of high radiofrequency treatment on the skin tissues of rabbits. AB - The aim of this study is to quantitatively investigate the short-term effects of RF tissue-tightening treatment in in vivo rabbit dermal collagen fibrils. These effects were measured at different energy levels and at varying pass procedures on the nanostructural response level using histology and AFM analysis. Each rabbit was divided into one of seven experimental groups, which included the following: control group, and six RF group according to RF energy (20 W and 40 W) and three RF pass procedures. The progressive changes in the diameter and D periodicity of rabbit dermal collagen fibrils were investigated in detail over a 7-day post-treatment period. The dermal tissues treated with the RF tissue tightening device showed more prominent inflammatory responses with inflammatory cell ingrowth compared to the control. This effect showed more prominent with the passage of day after treatment. Although an increase in the diameter and D periodicity of dermal collagen fibrils was identified immediately after the RF treatment, a decrease in the morphology of dermal collagen fibrils continued until post-operative day 7. Furthermore, RF treatment led to the loss of distinct borders. Increases in RF energy with the same pass procedure, as well as an increase in the number of RF passes, increased the occurrence of irreversible collagen fibril injury. A multiple-pass treatment at low energy rather than a single-pass treatment at high energy showed a large amount of collagen fibrils contraction at the nanostructural level. PMID- 22037868 TI - PAX3-FOXO1 induces cannabinoid receptor 1 to enhance cell invasion and metastasis. AB - Alveolar rhabdomyosarcoma (ARMS) is a muscle-derived childhood tumor characterized by production of oncogenic PAX3/7-FOXO1 chimeric transcription factors. While downstream targets of the PAX3-FOXO1 oncoprotein in ARMS have been defined, the functional relevance of these targets is unclear. Here, we show that upregulation of the cannabinoid receptor 1 (Cnr1/Cb1) by PAX3-FOXO1 in mouse primary myoblasts and ARMS cell lines, contributes to PAX3-FOXO1 phenotypes, both in vivo and in vitro. In primary myoblasts, Cnr1 was dispensable for PAX3-FOXO1 to mediate cell proliferation, differentiation, or transformation; however, Cnr1 function was essential to increase the invasive capacity conferred by PAX3-FOXO1 overexpression in these cells. Genetic or pharmacologic abrogation of Cnr1 inhibited the enhanced basement membrane invasion induced by PAX3-FOXO1. Cnr1 loss by either route also dramatically reduced lung metastasis formation. Taken together, our findings strongly implicate Cnr1 as a novel tractable target to inhibit ARMS invasion and metastasis. PMID- 22037866 TI - Genes and the ageing muscle: a review on genetic association studies. AB - Western populations are living longer. Ageing decline in muscle mass and strength (i.e. sarcopenia) is becoming a growing public health problem, as it contributes to the decreased capacity for independent living. It is thus important to determine those genetic factors that interact with ageing and thus modulate functional capacity and skeletal muscle phenotypes in older people. It would be also clinically relevant to identify 'unfavourable' genotypes associated with accelerated sarcopenia. In this review, we summarized published information on the potential associations between some genetic polymorphisms and muscle phenotypes in older people. A special emphasis was placed on those candidate polymorphisms that have been more extensively studied, i.e. angiotensin converting enzyme (ACE) gene I/D, alpha-actinin-3 (ACTN3) R577X, and myostatin (MSTN) K153R, among others. Although previous heritability studies have indicated that there is an important genetic contribution to individual variability in muscle phenotypes among old people, published data on specific gene variants are controversial. The ACTN3 R577X polymorphism could influence muscle function in old women, yet there is controversy with regards to which allele (R or X) might play a 'favourable' role. Though more research is needed, up-to-date MSTN genotype is possibly the strongest candidate to explain variance among muscle phenotypes in the elderly. Future studies should take into account the association between muscle phenotypes in this population and complex gene-gene and gene-environment interactions. PMID- 22037869 TI - Phosphorylation of carbonic anhydrase IX controls its ability to mediate extracellular acidification in hypoxic tumors. AB - In the hypoxic regions of a tumor, carbonic anhydrase IX (CA IX) is an important transmembrane component of the pH regulatory machinery that participates in bicarbonate transport. Because tumor pH has implications for growth, invasion, and therapy, determining the basis for the contributions of CA IX to the hypoxic tumor microenvironment could lead to new fundamental and practical insights. Here, we report that Thr443 phosphorylation at the intracellular domain of CA IX by protein kinase A (PKA) is critical for its activation in hypoxic cells, with the fullest activity of CA IX also requiring dephosphorylation of Ser448. PKA is activated by cAMP, which is elevated by hypoxia, and we found that attenuating PKA in cells disrupted CA IX-mediated extracellular acidification. Moreover, following hypoxia induction, CA IX colocalized with the sodium-bicarbonate cotransporter and other PKA substrates in the leading edge membranes of migrating tumor cells, in support of the concept that bicarbonate metabolism is spatially regulated at cell surface sites with high local ion transport and pH control. Using chimeric CA IX proteins containing heterologous catalytic domains derived from related CA enzymes, we showed that CA IX activity was modulated chiefly by the intracellular domain where Thr443 is located. Our findings indicate that CA IX is a pivotal mediator of the hypoxia-cAMP-PKA axis, which regulates pH in the hypoxic tumor microenvironment. PMID- 22037870 TI - The LMP7-K allele of the immunoproteasome exhibits reduced transcript stability and predicts high risk of colon cancer. AB - Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism of the immunoproteasome subunits LMP2 and LMP7 and of the transporters associated with antigen processing (TAP1 and TAP2) in two independently collected panels of colorectal carcinoma patients (N(1) = 112, N(2) = 62; controls, N = 165). High risk of colon cancer was associated with the LMP7-K/Q genotype (OR = 8.10, P = 1.10 * 10(-11)) and low risk with the LMP7-Q/Q genotype (OR = 0.10, P = 5.97 * 10(-13)). The basis for these distinct associations of LMP7 genotypes was functionally assessed by IFN-gamma stimulation of colon carcinoma cell lines (N = 10), followed by analyses of mRNA expression of HLA class I, TAP1, TAP2, and LMP7, with real-time PCR. Whereas induction of HLA-B, TAP1, and TAP2 was comparable in all cell lines, transcript amounts of LMP7-Q increased 10-fold, but of LMP7-K only 3.8-fold. This correlated with a reduced transcript stability of LMP7-K (t(1/2) ~ 7 minutes) compared with LMP7-Q (t(1/2) ~ 33 minutes). In addition, LMP7-Q/Q colon carcinoma cells increased (the peptide based) HLA class I surface expression significantly after IFN-gamma stimulation, whereas LMP7-Q/K and LMP7-K/K carcinoma cells showed minimal (<20%) changes. These results suggest that the presence of LMP7-K can reduce the formation of immunoproteasomes and thus peptide processing, followed by reduced peptide-HLA presentation, a crucial factor in the immune response against cancer. PMID- 22037871 TI - Egfl7 promotes tumor escape from immunity by repressing endothelial cell activation. AB - Downregulating the leukocyte adhesion molecules expressed by endothelial cells that line tumor blood vessels can limit the entry of immune effector cells into the tumor mass, thereby contributing to tumoral immune escape. Egfl7 (also known as VE-statin) is a secreted protein specifically expressed by endothelial cells in normal tissues and by cancer cells in various human tumors. High levels of Egfl7 correlate with higher tumor grade and poorer prognosis. Here we show that expression of Egfl7 in breast and lung carcinoma cells accelerates tumor growth and metastasis in immunocompetent mice but not in immunodeficient mice. Tumors expressing Egfl7 were infiltrated relatively poorly by immune cells and were characterized by reduced levels of immunostimulatory cytokines [IFN-gamma, interleukin-12 (IL-12)] and fewer endothelial adhesion molecules [intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)]. In vitro studies revealed that Egfl7 inhibited the expression of leukocyte adhesion molecules by endothelial cells, preventing lymphocyte adhesion. In contrast, Egfl7 did not exert any effects on immune cell activation. Human breast cancer lesions expressing high levels of Egfl7 also expressed less ICAM-1 and VCAM-1 in their blood vessels, also indicating an inverse correlation between expression levels of Egfl7 and IFN-gamma. Thus, Egfl7 expression in tumors promotes tumor progression by reducing the expression of endothelial molecules that mediate immune cell infiltration. Our findings highlight a novel mechanism through which tumors escape immune control. PMID- 22037872 TI - Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells. AB - Amplification of chromosome 8q22, which includes the gene for lysosomal associated transmembrane protein LAPTM4B, has been linked to de novo anthracycline resistance in primary breast cancers with poor prognosis. LAPTM4B overexpression can induce cytosolic retention of anthracyclines and decrease drug induced DNA damage. In this study, we tested the hypothesis that LAPTM4B may contribute to tumor cell growth or survival in the absence of a chemotherapeutic exposure. In mammary cells, LAPTM4B protein was localized in lysosomes where its depletion increased membrane permeability, pH, cathepsin release, and cellular apoptosis. Loss of LAPTM4B also inhibited later stages of autophagy by blocking maturation of the autophagosome, thereby rendering cells more sensitive to nutrient deprivation or hypoxia. Conversely, enforced overexpression of LAPTM4B promoted autophagic flux and cell survival during in vitro starvation and stimulated more rapid tumor growth in vivo. Together, our results indicate that LAPTM4B is required for lysosome homeostasis, acidification, and function, and that LAPTM4B renders tumor cells resistant to lysosome-mediated cell death triggered by environmental and genotoxic stresses. PMID- 22037874 TI - Variations in HSPA1B at 6p21.3 are associated with lung cancer risk and prognosis in Chinese populations. AB - The heat shock protein Hsp70 is crucial for regulating cellular homeostasis in stressed cells. Although the tumorigenic potential and prognostic applications of Hsp70 have been widely investigated, it remains unclear whether genetic variations of the human isoforms HSPA1L, HSPA1A, and HSPA1B are associated with cancer risk and prognosis. In this study, we genotyped six tagSNPs in these genes in 1,152 paired patients with lung cancer and controls, and then validated the results in additional cohorts of 1,781 patients with lung cancer and 1,038 controls. In addition, we evaluated the associations of these tagSNPs with survival in 330 patients with advanced non-small cell lung cancer (NSCLC) with additional validation in another 331 patients with advanced NSCLC. Functions of the risk variants identified were investigated using cell-based reporter assays. We found that the HSPA1B rs6457452T allele was associated with increased lung cancer risk compared with the rs6457452C allele in both data sets and also pooled analysis (adjusted OR = 1.41; P = 2.8 * 10(-5)). The HSPA1B rs2763979TT genotype conferred poor survival outcomes for patients with advanced NSCLC in two independent cohorts and pooled analysis [adjusted hazard ratio (HR) = 1.80, 1.61, and 1.66; P = 0.013, 0.036, and 0.002, respectively]. Lastly, we also found that the rs2763979T and rs6457452T alleles were each sufficient to reduce expression of transcriptional reporter constructs, when compared with the rs2763979C and rs6457452C alleles, respectively. Taken together, our findings define that functional HSPA1B variants are associated with lung cancer risk and survival. These Hsp70 genetic variants may offer useful biomarkers to predict lung cancer risk and prognosis. PMID- 22037873 TI - Autophagy enhanced by microtubule- and mitochondrion-associated MAP1S suppresses genome instability and hepatocarcinogenesis. AB - Dysfunctional autophagy is associated with tumorigenesis; however, the relationship between the two processes remains unclear. In the present study, we showed that MAP1S levels immediately become elevated in response to diethylnitrosamine-induced or genome instability-driven metabolic stress in a murine model of hepatocarcinoma. Upregulation of MAP1S enhanced autophagy to remove aggresomes and dysfunctional organelles that trigger DNA double-strand breaks and genome instability. The early accumulation of an unstable genome before signs of tumorigenesis indicated that genome instability caused tumorigenesis. After tumorigenesis, tumor development triggered the activation of autophagy to reduce genome instability in tumor foci. We, therefore, conclude that an increase in MAP1S levels triggers autophagy to suppress genome instability such that both the incidence of diethylnitrosamine-induced hepatocarcinogenesis and malignant progression are suppressed. Taken together, the data establish a link between MAP1S-enhanced autophagy and suppression of genomic instability and tumorigenesis. PMID- 22037875 TI - Cyclin D3 compensates for the loss of cyclin D1 during ErbB2-induced mammary tumor initiation and progression. AB - Cyclin D1 regulates cell proliferation and is a candidate molecular target for breast cancer therapy. This study addresses whether Cyclin D1 is indispensable for ErbB2-associated mammary tumor initiation and progression using a breast cancer model in which this cell-cycle regulator can be genetically ablated prior to or after neoplastic transformation. Deficiency in Cyclin D1 delayed tumor onset but did not prevent the occurrence of mammary cancer in mice overexpressing wild-type ErbB2. The lack of Cyclin D1 was associated with a compensatory upregulation of Cyclin D3, which explains why the targeted downregulation of Cyclin D1 in established mammary tumors had no effect on cancer cell proliferation. Cyclin D1 and D3 are overexpressed in human breast cancer cell lines and primary invasive breast cancers, and Cyclin D3 frequently exceeded the expression of Cyclin D1 in ErbB2-positive cases. The simultaneous inhibition of both cyclins in mammary tumor cells reduced cancer cell proliferation in vitro and decreased the tumor burden in vivo. Collectively, the results of this study suggest that only the combined inhibition of Cyclin D1 and D3 might be a suitable strategy for breast cancer prevention and therapy. PMID- 22037876 TI - Apoptosis inhibitor ARC promotes breast tumorigenesis, metastasis, and chemoresistance. AB - Apoptosis repressor with caspase recruitment domain (ARC) inhibits both death receptor- and mitochondrial/ER-mediated pathways of apoptosis. Although expressed mainly in terminally differentiated cells, ARC is markedly upregulated in a variety of human cancers, where its potential contributions have not yet been defined. In this study, we provide evidence of multiple critical pathophysiologic functions for ARC in breast carcinogenesis. In the polyoma middle T-antigen (PyMT) transgenic mouse model of breast cancer, in which endogenous ARC is strongly upregulated, deletion of the ARC-encoding gene nol3 decreased primary tumor burden without affecting tumor onset or multiplicity. More notably, ARC deficiency also limited tumor cell invasion and the number of circulating cancer cells, markedly reducing the number of lung metastases. Conversely, ectopic overexpression of ARC in a PyMT-derived metastatic breast cancer cell line increased invasion in vitro and lung metastasis in vivo. We confirmed these results in a humanized orthotopic model based on MDA-MB-231-derived LM2 metastatic breast cancer cells, in which RNAi-mediated knockdown of ARC levels was shown to reduce tumor volume, local invasion, and lung metastases. Lastly, we found that endogenous levels of ARC conferred chemoresistance in primary tumors and invading cell populations. Our results establish that ARC promotes breast carcinogenesis by driving primary tumor growth, invasion, and metastasis as well as by promoting chemoresistance in invasive cells. PMID- 22037878 TI - Thrombospondin-1 triggers cell migration and development of advanced prostate tumors. AB - The antitumor effects of pharmacologic inhibitors of angiogenesis are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here, we reevaluated the role of the endogenous antiangiogenic thrombospondin 1 (TSP1) in prostate carcinomas in which angiogenesis is an active process. In xenografted tumors, we observed that TSP1 altogether inhibited angiogenesis and fostered tumor development. Our results show that TSP1 is a potent stimulator of prostate tumor cell migration. This effect required CD36, which also mediates TSP1 antiangiogenic activity, and was mimicked by an antiangiogenic TSP1-derived peptide. As suspected for pharmacologic inhibitors of angiogenesis, the TSP1 capacities to increase hypoxia and to trigger cell migration are thus inherently linked. Importantly, although antiangiogenic TSP1 increases hypoxia in vivo, our data show that, in turn, hypoxia induced TSP1, thus generating a vicious circle in prostate tumors. In radical prostatectomy specimens, we found TSP1 expression significantly associated with invasive tumors and with tumors which eventually recurred. TSP1 may thus help select patients at risk of prostate-specific antigen relapse. Together, the data suggest that intratumor disruption of the hypoxic cycle through TSP1 silencing will limit tumor invasion. PMID- 22037879 TI - Pharmacokinetics, metabolism and excretion of [(14)C]-lenalidomide following oral administration in healthy male subjects. AB - PURPOSE: Assessment of the absorption, metabolism and excretion of [(14)C] lenalidomide in healthy male subjects following a single oral dose. METHODS: Six healthy male subjects were administered a single 25 mg oral suspension dose of [(14)C]-lenalidomide. Blood (plasma), semen and excreta were collected. Mass balance assessments were done by radioactivity measurements. Metabolite profiling and quantitation were accomplished using liquid chromatography with mass spectrometric and radiochemical detection. RESULTS: [(14)C]-Lenalidomide was rapidly absorbed (T (max) 0.77-1.0 h), and the levels declined with a terminal half-life of approximately 3 h, with similar profiles for total blood and plasma radioactivity as well as plasma lenalidomide. The whole blood to plasma radioactivity exposure levels were comparable, suggesting equal distribution between plasma and blood cells. On average, 94% of the administered radioactivity was recovered within 10 days, with >88% recovered within 24 h. Urinary excretion was the primary route of elimination (90% of radioactive dose), with minor amounts excreted in feces (4%). Semen contained a small amount of the radioactive dose (0.0062%). Lenalidomide was the primary radioactive component in plasma (92% of the [(14)C]-area under the concentration-time curve) and urine (>90% of the radioactivity in urine). The remaining radioactivity was composed of primarily two metabolites: 5-hydroxy-lenalidomide and N-acetyl-lenalidomide, each accounting for less than 5% of the total radioactivity as well as lenalidomide levels in plasma and excreta. CONCLUSIONS: In summary, following oral administration, lenalidomide is highly absorbed and bioavailable, metabolized minimally, and eliminated predominantly via urinary excretion in the unchanged form in humans. PMID- 22037877 TI - Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium. AB - Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have shown that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma. PMID- 22037880 TI - ABT-263 sensitizes TRAIL-resistant hepatocarcinoma cells by downregulating the Bcl-2 family of anti-apoptotic protein. AB - PURPOSE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its selective cytotoxicity to transformed cells. However, most human hepatocellular carcinomas (HCC) develop resistance to TRAIL. Thus, there is an urgent need to investigate the molecular targets and the underlying mechanisms that may be involved in overriding the resistance of tumor cells to TRAIL. METHODS: Cell viability analysis was performed in HCC cells after treatment with TRAIL and/or ABT-263. Flow cytometry was used to assess apoptosis. The expression of caspases and members of the Bcl-2 family was examined through immunoblot analysis. Finally, the viability of cancer cells transfected with a plasmid containing HBx (hepatitis B virus X protein) following treatment with TRAIL was also measured. RESULTS: In this study, we demonstrate that ABT-263, a potent and orally bioavailable inhibitor of the Bcl-2 family, was able to reverse the resistance of hepatocarcinoma cell lines to TRAIL-induced apoptosis, while sparing normal liver cells. The molecular mechanism of the reversal in resistance may be attributed to the inhibition by ABT-263 of anti-apoptosis proteins of the Bcl-2 family. In addition, we determined that HBx was able to sensitize TRAIL resistant hepatocarcinoma Huh7 cells. CONCLUSIONS: These findings provide a novel insight into the clinical application of TRAIL-induced apoptosis of HCC cells. PMID- 22037881 TI - Intrapleural paclitaxel for malignant pleural effusion from ovarian and breast cancer: a phase II study with pharmacokinetic analysis. AB - INTRODUCTION: Malignant pleural effusion (MPE) is a frequent complication in many types of tumors diminishing the patient's ability to perform activities. Despite various studies on talc treatment, some doubts about its safety and effectiveness remain, so the search for a more ideal intrapleural agent continues. We analyzed the effectiveness and safety of intrapleural paclitaxel in ovarian and breast cancer patients. PATIENTS AND METHODS: The primary endpoint was overall response rate (ORR); secondary objectives included time to progression (TTP), overall survival (OS) and safety of intrapleural paclitaxel. Pharmacokinetics of the drug was also analyzed. After drainage of pleural effusion and lung re-expansion, paclitaxel 120 mg/m(2) diluted in normal saline was infused through a preinserted catheter which was immediately closed and reopened 24 h later. Blood and pleural fluid samples were collected 1, 4 and 24 h after the end of paclitaxel instillation. When MPE was less than 200 ml/24 h the catheter was removed. Chest radiographs were performed at the beginning of intrapleural paclitaxel, at 1 and 2 months later or with clinical deterioration. RESULTS: We enrolled 18 patients with recurrent MPE: 11 with ovarian cancer and 7 with breast cancer. ORR was 77.8% at 1 month and 88.8%. at 2 months. Median TTP was 5.5 months (CI 95% 0.9 10.1) and median OS was 8.9 months (CI 95% 0.1-17.6). Patients achieving a complete response obtained a statistically significant longer survival than did patients with partial response or progressive disease. Chest pain, fever, and dyspnea were the most frequent side effects. Intrapleural paclitaxel concentrations were very high (mean +/- SD = 478 +/- 187 mg/l) and declined slowly (mean 24 h reduction ~30%). Detectable but low taxol plasma levels were found in most patients (mean +/- SD = 0.045 +/- 0.073 mg/l). CONCLUSION: Intrapleural paclitaxel is a safe and effective palliative treatment for MPE from breast and ovarian cancers and may be integrated with systemic chemotherapy. PMID- 22037882 TI - Clinical trial design in brain metastasis: approaches for a unique patient population. AB - Clinical trials in brain metastases present challenges and opportunities unique to this patient population. With the increase in awareness and screening for brain metastases, smaller and often asymptomatic lesions are detected, creating the opportunity for trials of pre-irradiation chemotherapy. The goal of earlier intervention is advanced by studies to prevent brain metastases in high-risk populations. Sequencing of systemic chemotherapy with experimental chemotherapy in the context of a clinical trial requires collaboration between the investigators and the treating medical oncologists beginning ideally during design of the study. Adaptive randomization improves the efficiency of randomized trials in the brain metastasis population. Finally, collaborative efforts between patients and physicians with the support from patient advocacy groups will help advance the quality and the clinical trial options for patients with brain metastases. PMID- 22037883 TI - [Lymphomatoid papulosis in a 2 1/2-year-old boy]. AB - Lymphomatoid papulosis (LyP) is a rare cutaneous lymphoproliferative disorder that has malignant histologic features and a benign clinical course. LyP is classified according to the WHO/EORTC classification for cutaneous lymphoma as a CD30-positive lymphoproliferative disorder. Few previous reports have detailed features of LyP in pediatric and adolescent patients, but LyP very rarely presents in early childhood. A 2 1/2-year-old boy presented with a 1-year history of recurrent papular and nodular lesions on the face and trunk. Clinical and histopathologic criteria lead to the diagnosis lymphomatoid papulosis. PMID- 22037884 TI - [Plexiform fibrohistiocytic tumor]. AB - Plexiform fibrohistiocytic tumor is a rare soft-tissue tumor with intermediate malignancy. It has a predilection for girls and young women. A 6-year-old girl presented with an indolent nodule in the right axilla first noticed six months earlier. Clinical and histopathological criteria led to the diagnosis plexiform fibrohistiocytic tumor. As relapses may occur and some cases of metastasis have been reported, lesions should be excised. Long-term follow-up is required to promptly identify any local recurrence as well as nodal and pulmonary metastases. PMID- 22037885 TI - Comparison of long-term clinical outcomes and costs between video-assisted thoracoscopic surgery and transcatheter amplatzer occlusion of the patent ductus arteriosus. AB - The current study was designed to compare long-term clinical outcomes and costs between video-assisted thoracoscopic surgery (VATS) and transcatheter Amplatzer occlusion (TAO). This study enrolled 294 patients with isolated patent ductus arteriosus (PDA) from April 2002 to April 2007, and 290 of these patients were followed up until April 2010. Of the 294 patients, 196 underwent VATS and 98 accepted TAO for PDA closure. The two groups were similar in terms of demographics and preoperative clinical characteristics. No cardiac deaths occurred in either group. All the patients in the VATS group had successful PDA closure, and 94 patients (94/98, 95.9%) in the TAO group had successful PDA occlusion. The incidence of acute procedure-related complications recorded was 1.5% in the VATS group compared with 10.2% in TAO group (P < 0.05). The cost per patient was $1,309.40 +/- $312.20 in the VATS group and $3,415.80 +/- $637.30 in the TAO group (P < 0.05). There were no cardiac deaths or newly occurring arrhythmias in either group during the fellow-up period. Up to the latest follow up, no late recanalization or residual shunting was documented, and heart structure returned to normal level in the VATS group. However, residual shunting was detected in four more TAO patients. This study confirmed the long-term safety and efficacy of VATS clipping of PDA. Compared with TAO, PDA interrupted with VATS can achieve both excellent clinical results and satisfying cost effectiveness. The cost for VATS is only a little more than one third the cost for TAO. PMID- 22037886 TI - Distribution and health-risk of polycyclic aromatic hydrocarbons in soils at a coking plant. AB - Nineteen soil samples were collected in and around Songshan coking plant in Guangdong province of China and analyzed for eighteen polycyclic aromatic hydrocarbons (PAHs) by gas chromatography-mass spectrometry (GC-MS). The total concentration of PAHs ranged from 2.36 to 1146.39 mg kg(-1) dry weight, varying significantly among the sampling sites, most individual PAHs were correlated with each other. A cluster analysis was performed to examine the correlation of PAH distribution, five groups were observed with sample types in the coking plant. 2 3 ring PAHs were predominant in group I and II, while 4-5 ring PAHs showed great abundance in group III, IV and V, which contributed to the distance from the emission sources in the coking plant and the behaviors of particle-bound and gaseous PAHs. The ratios of Flu : (Flu + Pyr), BaA : (BaA + Chr), InP : (InP + BgP) and Ant : (Ant + Phen) ratios were 0.51-0.87, 0.16-0.89, 0.47-0.68 and 0.03 0.60, respectively. The total index of all studied soils was > 6, indicating that the source of the PAHs in coking plant soils were from the pyrolysis processes. Health risk assessments were carried out by dermal PAH exposure data to quantify cancer risk. The resultant lifetime exposure levels due to TEQ(BaP) desorbed onto skin for workers ranged from 2.25 * 10(-7) to 7.86 * 10(-5) mg kg(-1) per day, and the estimated cancer risks were between 8.45 * 10(-6) and 2.94 * 10(-3), indicating that the dermal exposures of PAHs to coking workers might be acceptable in most soil sites. PMID- 22037887 TI - The future of health IT innovation and informatics: a report from AMIA's 2010 policy meeting. AB - While much attention has been paid to the short-term impact that widespread adoption of health information technology (health IT) will have on the healthcare system, there is a corresponding need to look at the long-term effects that extant policies may have on health IT system resilience, innovation, and related ethical, social/legal issues. The American Medical Informatics Association's 2010 Health Policy Conference was convened to further the national discourse on the issues surrounding these longer-term considerations. Conference participants self selected into three broad categories: resilience in healthcare and health IT; ethical, legal, and social challenges; and innovation, adoption, and sustainability. The discussions about problem areas lead to findings focusing on the lack of encouragement for long-term IT innovation that may result from current health IT policies; the potential impact of uneven adoption of health IT based on the exclusions of the current financial incentives; the weaknesses of contingency and risk mitigation planning that threaten system resilience; and evolving standards developed in response to challenges relating to the security, integrity, and availability of electronic health information. This paper discusses these findings and also offers recommendations that address the interwoven topics of innovation, resilience, and adoption. The goal of this paper is to encourage public and private sector organizations that have a role in shaping health information policy to increase attention to developing a national strategy that assures that health IT innovation and resilience are not impeded by shorter-term efforts to implement current approaches emphasizing adoption and meaningful use of electronic health records. PMID- 22037888 TI - Provider and pharmacist responses to warfarin drug-drug interaction alerts: a study of healthcare downstream of CPOE alerts. AB - OBJECTIVE: To categorize the appropriateness of provider and pharmacist responses to warfarin critical drug-drug interaction (cDDI) alerts, assess responses and actions to the cDDI, and determine the occurrence of warfarin adverse drug events (ADE) after alerts. DESIGN: An 18-month, retrospective study of acute care admissions at a single Veterans Affairs medical center using computerized provider order entry (CPOE). MEASUREMENTS: Patients included had at least one warfarin cDDI alert. Chart reviews included baseline laboratory values and demographics, provider actions, patient outcomes, and associated factors, including other interacting medications and number of simultaneously processed alerts. RESULTS: 137 admissions were included (133 unique patients). Amiodarone, vitamin E in a multivitamin, sulfamethoxazole, and levothyroxine accounted for 75% of warfarin cDDI. Provider responses were clinically appropriate in 19.7% of admissions and pharmacist responses were appropriate in 9.5% of admissions. There were 50 ADE (36.6% of admissions) with warfarin; 80% were rated as having no or mild clinical effect. An increased number of non-critical alerts at the time of the reference cDDI alert was the only variable associated with an inappropriate provider response (p=0.01). LIMITATIONS: This study was limited by being a retrospective review and the possibility of confounding variables, such as other interacting medications. CONCLUSION: The large number of CPOE alerts may lead to inappropriate responses by providers and pharmacists. The high rate of ADE suggests a need for improved medication management systems for patients on warfarin. This study highlights the possibility of alert fatigue contributing to the high prevalence of inappropriate alert over-ride text responses. PMID- 22037889 TI - Medication administration quality and health information technology: a national study of US hospitals. AB - OBJECTIVE: To determine whether the use of computerized physician order entry (CPOE) and electronic medication administration records (eMAR) is associated with better quality of medication administration at medium-to-large acute-care hospitals. DATA/STUDY SETTING: A retrospective cross-sectional analysis of data from three sources: CPOE/eMAR usage from HIMSS Analytics (2010), medication quality scores from CMS Hospital Compare (2010), and hospital characteristics from CMS Acute Inpatient Prospective Payment System (2009). The analysis focused on 11 quality indicators (January-December 2009) at 2603 medium-to-large (>= 100 beds), non-federal acute-care hospitals measuring proportion of eligible patients given (or prescribed) recommended medications for conditions, including acute myocardial infarction, heart failure, and pneumonia, and surgical care improvement. Using technology adoption by 2008 as reference, hospitals were coded: (1) eMAR-only adopters (n=986); (2) CPOE-only adopters (n=115); and (3) adopters of both technologies (n=804); with non-adopters of both technologies as reference group (n=698). Hospitals were also coded for duration of use in 2-year increments since technology adoption. Hospital characteristics, historical measure-specific patient volume, and propensity scores for technology adoption were used to control for confounding factors. The analysis was performed using a generalized linear model (logit link and binomial family). PRINCIPAL FINDINGS: Relative to non-adopters of both eMAR and CPOE, the odds of adherence to all measures (except one) were higher by 14-29% for eMAR-only hospitals and by 13-38% for hospitals with both technologies, translating to a marginal increase of 0.4 2.0 percentage points. Further, each additional 2 years of technology use was associated with 6-15% higher odds of compliance on all medication measures for eMAR-only hospitals and users of both technologies. CONCLUSIONS: Implementation and duration of use of health information technologies are associated with improved adherence to medication guidelines at US hospitals. The benefits are evident for adoption of eMAR systems alone and in combination with CPOE. PMID- 22037890 TI - Direct2Experts: a pilot national network to demonstrate interoperability among research-networking platforms. AB - Research-networking tools use data-mining and social networking to enable expertise discovery, matchmaking and collaboration, which are important facets of team science and translational research. Several commercial and academic platforms have been built, and many institutions have deployed these products to help their investigators find local collaborators. Recent studies, though, have shown the growing importance of multiuniversity teams in science. Unfortunately, the lack of a standard data-exchange model and resistance of universities to share information about their faculty have presented barriers to forming an institutionally supported national network. This case report describes an initiative, which, in only 6 months, achieved interoperability among seven major research-networking products at 28 universities by taking an approach that focused on addressing institutional concerns and encouraging their participation. With this necessary groundwork in place, the second phase of this effort can begin, which will expand the network's functionality and focus on the end users. PMID- 22037891 TI - Implementation of an innovative, integrated electronic medical record (EMR) and public health information exchange for HIV/AIDS. AB - Louisiana is severely affected by HIV/AIDS, ranking fifth in AIDS rates in the USA. The Louisiana Public Health Information Exchange (LaPHIE) is a novel, secure bi-directional public health information exchange, linking statewide public health surveillance data with electronic medical record data. LaPHIE alerts medical providers when individuals with HIV/AIDS who have not received HIV care for >12 months are seen at any ambulatory or inpatient facility in an integrated delivery network. Between 2/1/2009 and 1/31/2011, 488 alerts identified 345 HIV positive patients. Of those identified, 82% had at least one CD4 or HIV viral load test over the study follow-up period. LaPHIE is an innovative use of health information exchange based on surveillance data and real time clinical messaging, facilitating rapid provider notification of those in need of treatment. LaPHIE successfully reduces critical missed opportunities to intervene with individuals not in care, leveraging information historically collected solely for public health purposes, not health care delivery, to improve public health. PMID- 22037892 TI - Utility of gene-specific algorithms for predicting pathogenicity of uncertain gene variants. AB - The rapid advance of gene sequencing technologies has produced an unprecedented rate of discovery of genome variation in humans. A growing number of authoritative clinical repositories archive gene variants and disease phenotypes, yet there are currently many more gene variants that lack clear annotation or disease association. To date, there has been very limited coverage of gene specific predictors in the literature. Here the evaluation is presented of "gene specific" predictor models based on a naive Bayesian classifier for 20 gene disease datasets, containing 3986 variants with clinically characterized patient conditions. The utility of gene-specific prediction is then compared with "all gene" generalized prediction and also with existing popular predictors. Gene specific computational prediction models derived from clinically curated gene variant disease datasets often outperform established generalized algorithms for novel and uncertain gene variants. PMID- 22037893 TI - Validation of a common data model for active safety surveillance research. AB - OBJECTIVE: Systematic analysis of observational medical databases for active safety surveillance is hindered by the variation in data models and coding systems. Data analysts often find robust clinical data models difficult to understand and ill suited to support their analytic approaches. Further, some models do not facilitate the computations required for systematic analysis across many interventions and outcomes for large datasets. Translating the data from these idiosyncratic data models to a common data model (CDM) could facilitate both the analysts' understanding and the suitability for large-scale systematic analysis. In addition to facilitating analysis, a suitable CDM has to faithfully represent the source observational database. Before beginning to use the Observational Medical Outcomes Partnership (OMOP) CDM and a related dictionary of standardized terminologies for a study of large-scale systematic active safety surveillance, the authors validated the model's suitability for this use by example. VALIDATION BY EXAMPLE: To validate the OMOP CDM, the model was instantiated into a relational database, data from 10 different observational healthcare databases were loaded into separate instances, a comprehensive array of analytic methods that operate on the data model was created, and these methods were executed against the databases to measure performance. CONCLUSION: There was acceptable representation of the data from 10 observational databases in the OMOP CDM using the standardized terminologies selected, and a range of analytic methods was developed and executed with sufficient performance to be useful for active safety surveillance. PMID- 22037894 TI - Autologous chondrocyte implantation for the treatment of chondral and osteochondral defects of the talus: a meta-analysis of available evidence. AB - PURPOSE: While autologous chondrocyte implantation (ACI) has become an established surgical treatment for cartilage defects of the knee, only little is known about the clinical outcome following ACI for chondral or osteochondral lesion of the ankle. To evaluate efficiency and effectiveness of ACI for talar lesions was aim of the present meta-analysis. METHODS: An OVID-based literature search was performed to identify any published clinical studies on autologous chondrocyte implantation (ACI) for the treatment of pathologies of the ankle including the following databases: MEDLINE, MEDLINE preprints, EMBASE, CINAHL, Life Science Citations, British National Library of Health, and Cochrane Central Register of Controlled Trials (CENTRAL). Literature search period was from the beginning of 1994 to February 2011. Of 54 studies that were identified, a total of 16 studies met the inclusion criteria of the present meta-analysis. Those studies were systematically evaluated. RESULTS: All studies identified represented case series (EBM Leven IV). 213 cases with various treatment for osteochondral and chondral defects with a mean size of 2.3 cm(2) (+/-0.6) have been reported. A total of 9 different scores have been used as outcome parameters. Mean study size was 13 patients (SD 10; range 2-46) with a mean follow-up of 32 +/- 27 months (range 6-120). Mean Coleman Methodology Score was 65 (SD 11) points. Overall clinical success rate was 89.9%. CONCLUSIONS: Evidence concerning the use of ACI for osteochondral and chondral defects of the talus is still elusive. Although clinical outcome as described in the studies available seems promising--with regard to a lack of controlled studies--a superiority or inferiority to other techniques such as osteochondral transplantation or microfracturing cannot be estimated. PMID- 22037895 TI - Talking about disability in prenatal genetic counseling: a report of two interactive workshops. AB - Women are commonly offered testing in pregnancy to determine the health of their baby. An important component of informed decision-making about prenatal testing is provision of relevant, accurate, meaningful information concerning the conditions that are being tested for--many of which, such as Down syndrome, are associated with a varying degree of physical and intellectual disability. A range of health professionals, including genetic counselors, may provide information and support throughout the testing process, but available data suggest that discussion of disability is frequently absent or limited. To investigate genetic counselors' perceptions of this situation and identify potential barriers to discussion we facilitated interactive workshops at the 2007 National Society of Genetic Counselors Annual Education Conference (NSGC) and the 2008 European Meeting on Psychosocial Aspects of Genetics (EMPAG). Working groups identified relevant psychosocial issues and impediments to discussion (NSGC) or used a two part scenario to promote discussion (EMPAG) and reported findings in notes and a closing plenary discussion. Inductive content analysis revealed that participants considered informed decision making to be a major reason for presenting information about disabilities in prenatal genetic counseling and endorsed the value of including information about daily life with Down syndrome and other disabilities. However, they identified three broad types of impediments to such discussion: counseling issues concerning the most appropriate manner to discuss disability under the complex circumstances of prenatal genetic counseling, less than optimal training and experience in addressing these issues, and perceived limitations in the participants' knowledge and understanding of life with disability. Our analysis of the responses from the workshop participants and additional thoughts on these issues have led us to develop recommendations for further research, training and clinical practice. PMID- 22037896 TI - Disability advocacy and reproductive choice: engaging with the expressivist objection. AB - This professional issues paper outlines the experience and value of engagement with disability advocates, philosophy scholars and bioethicists for spirited debate of issues such as modern eugenics, the expressivist objection and reproductive choice. This process for one group of individuals, undoubtedly prompted deeper examination and questioning of some long held personal and professional views, for all participants. For this author, engagement in the "Disability Rights-Genetic Counseling Interest Group" over a full year resulted in several positive changes in genetic counselling practice as well as the development of meaningful, robust philosophical defence of the dual roles in genetic counseling; advocacy for those with disabilities, and facilitation of a full range of reproductive choices. PMID- 22037897 TI - Effects of a documentary film on public stigma related to mental illness among genetic counselors. AB - Many people, including genetic counselors, have been found to hold stigmatizing attitudes towards people with mental illnesses. We aimed to determine whether these attitudes could be changed by exposing genetic counselors and genetic counseling students to a documentary film about people with mental illness. We screened the documentary at the 2010 North American conferences for genetic counselors. Immediately before (T1), immediately after (T2), and one month after (T3) watching the documentary, participants self-rated their comfort with asking patients about mental illness, and they completed scales measuring two aspects of stigma: stereotype endorsement, and desire for social distance. A total of 87 T1 and T2 questionnaires, and 39 T3 questionnaires were returned. At T2 and T3, 34.5% and 48.7% respectively reported feeling more comfortable to ask patients about mental illness. Scores on the social distance and stereotype endorsement scales decreased significantly from T1 to T2, but returned to initial levels at T3. The findings suggest the documentary increased genetic counselors' and genetic counseling students' comfort with asking about mental illness and temporarily decreased their stigmatizing attitudes. PMID- 22037898 TI - Commentary: how individual and profession-level factors influence discussion of disability in prenatal genetic counseling. AB - Hodgson and Weil (Journal of Genetic Counseling, 2011) reports on two interactive workshops in which genetic counselors identified a broad set of counseling issues that may be impediments to promoting an adequate discussion of disability in prenatal genetic counseling. The present commentary discusses two factors that we infer underlie these counseling issues. First, countertransference concerning disability, which is normal and expected, may influence genetic counselors' decisions about raising and exploring the complex topic of disability in prenatal genetic counseling. Second, the limited involvement of the profession of genetic counseling in the complex social and ethical issues of disability provide little guidance to the individual genetic counselor with respect to discussing disability in prenatal diagnosis counseling. We suggest both factors must be acknowledged and addressed in order to adequately implement the recommendations presented in Hodgson and Weil (Journal of Genetic Counseling, 2011) as well as other efforts to increase discussion of disability in prenatal diagnosis counseling in the service of informed decision making. PMID- 22037899 TI - Information related to prenatal genetic counseling: interpretation by adolescents, effects on risk perception and ethical implications. AB - Being raised in the genomic era may not only increase knowledge of available genetic testing but may also have an impact on how genetic information is perceived. However, little is known about how current adolescents react to the language commonly used by health care professionals providing prenatal counseling. In addition, as risk communication is related to numbers and figures, having different educational backgrounds may be associated with variability in risk perceptions. In order to investigate these issues, a previously developed questionnaire studying different ways of being told about hypothetical anomalies in a baby and corresponding risks (Abramsky and Fletcher Prenatal Diagnosis 22(13):1188-1194, 2002) was administered to high-school students in Sweden. A total of 344 questionnaires were completed by students belonging to a natural science or a social science program. The data show that teenage participants found technical jargon and words such as rare and abnormal more worrying than the presented comparison terms. Negative framing effects and perception differences related to numeric risk formats were also present. Additionally, participants' gender and educational program did not seem to have an effect on risk assessment. In addition to reporting the questionnaire results, we discuss the ethical implications of the data based on the norm of non-directiveness and make some recommendations for practice. In general, genetic counselors should be aware that the language used within clinical services can be influential on this group of upcoming counselees. PMID- 22037900 TI - Laser desorption/ionization on the layer of graphene nanoparticles coupled with mass spectrometry for characterization of polymers. AB - A novel method for the characterization of polymers by laser desorption/ionization on the layer of graphene nanoparticles coupled with time-of flight mass spectrometry was demonstrated. Various polymers including polypropylene glycol, polystyrene and polymethyl methacrylate with average molecular weights from 425 to 3500 Da were analyzed. PMID- 22037901 TI - The survival of metallic residues from gunshot wounds in cremated bone: a radiological study. AB - In literature, many studies have been performed in order to investigate the presence of GSR ("gunshot residue") and metallic residues in general with radiological techniques on several types of material, but the survival of metallic residues on charred samples has never been systematically performed. In this study, 31 adult bovine ribs underwent a shooting test. Every rib was shot with a single bullet, at a near-contact shooting distance, using two kinds of projectile: 17 samples were shot with a full metal-jacketed bullet and the remaining 14 with an unjacketed bullet. After the shooting test, every rib underwent a "charring cycle" in an electric oven up to 800 degrees C. Every sample underwent radiological investigation with conventional radiography, before and after the burning process, to evaluate any changes in number and distribution of metallic residues. Radiographs showed survival of radiopaque residues in every sample, even after the charring process, especially when the bullet used was of the unjacketed type. PMID- 22037902 TI - Epigenetics DNA methylation in the core ataxin-2 gene promoter: novel physiological and pathological implications. AB - Pathogenic CAG (cytosine-adenine-guanine) expansions beyond certain thresholds in the ataxin-2 (ATXN2) gene cause spinocerebellar ataxia type 2 (SCA2) and were shown to contribute to Parkinson disease, amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Regulation of ATXN2 gene expression and the function of the protein product are not known. SCA2 exhibits an inverse correlation between the size of the CAG repeat and the age at disease onset. However, a wide range of age at onset are typically observed, with CAG repeat number alone explaining only partly this variability. In this study, we explored the hypothesis that ATXN2 levels could be controlled by DNA methylation and that the derangement of this control may lead to escalation of disease severity and influencing the age at onset. We found that CpG methylation in human ATXN2 gene promoter is associated with pathogenic CAG expansions in SCA2 patients. Different levels of methylation in a SCA2 pedigree without an intergenerational CAG repeat instability caused the disease anticipation in a SCA2 family. DNA methylation also influenced the disease onset in SCA2 homozygotes and SCA3 patients. In conclusion, our study points to a novel regulatory mechanism of ATXN2 expression involving an epigenetic event resulting in differential disease course in SCA2 patients. PMID- 22037904 TI - Mammography capacity and appointment wait times: barriers to breast cancer screening. AB - OBJECTIVE: To assess the impact of mammography capacity on appointment wait times. METHODS: We surveyed by telephone all mammography facilities federally certified in 2008 in California, Connecticut, Georgia, Iowa, New Mexico, and New York using a simulated patient format. County-level mammography capacity, defined as the number of mammography machines per 10,000 women aged 40 and older, was estimated from FDA facility certification records and US Census data. RESULTS: 1,614 (86%) of 1,882 mammography facilities completed the survey. Time until next available screening mammogram appointment was <1 week at 55% of facilities, 1-4 weeks at 34% of facilities, and >1 month at 11% of facilities. Facilities in counties with lower capacity had longer wait times, and a one-unit increase in county capacity was associated with 21% lower odds of a facility reporting a wait time >1 month (p < 0.01). There was no association between wait time and the availability of evening or weekend appointments or digital mammography. CONCLUSION: Lower mammography capacity is associated with longer wait times for screening mammograms. IMPACT: Enhancement of mammography resources in areas with limited capacity may reduce wait times for screening mammogram appointments, thereby increasing access to services and rates of breast cancer screening. PMID- 22037903 TI - Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network. AB - White blood cell count (WBC) is unique among identified inflammatory predictors of chronic disease in that it is routinely measured in asymptomatic patients in the course of routine patient care. We led a genome-wide association analysis to identify variants associated with WBC levels in 13,923 subjects in the electronic Medical Records and Genomics (eMERGE) Network. We identified two regions of interest that were each unique to subjects of genetically determined ancestry to the African continent (AA) or to the European continent (EA). WBC varies among different ancestry groups. Despite being ancestry specific, these regions were identifiable in the combined analysis. In AA subjects, the region surrounding the Duffy antigen/chemokine receptor gene (DARC) on 1q21 exhibited significant association (p value = 6.71e-55). These results validate the previously reported association between WBC and of the regulatory variant rs2814778 in the promoter region, which causes the Duffy negative phenotype (Fy-/-). A second missense variant (rs12075) is responsible for the two principal antigens, Fya and Fyb of the Duffy blood group system. The two variants, consisting of four alleles, act in concert to produce five antigens and subsequent phenotypes. We were able to identify the marginal and novel interaction effects of these two variants on WBC. In the EA subjects, we identified significantly associated SNPs tagging three separate genes in the 17q21 region: (1) GSDMA, (2) MED24, and (3) PSMD3. Variants in this region have been reported to be associated with WBC, neutrophil count, and inflammatory diseases including asthma and Crohn's disease. PMID- 22037905 TI - The association of cigarette smoking with gastric cancer: the multiethnic cohort study. AB - PURPOSE: The purpose of this study is to investigate the association of cigarette smoking with gastric cancer. METHODS: Over 215,000 men and women, representing five ethnic groups (African Americans, Japanese Americans, Latino Americans, Native Hawaiians, and Whites), completed a mailed questionnaire, 1993-1996. After an average follow-up of 7.3 years, 454 men and 242 women were diagnosed with gastric adenocarcinoma. Cox proportional hazard models were used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. RESULTS: Current cigarette smokers had elevated hazard ratios compared with never smokers among men (HR = 1.98; 95% CI 1.46-2.70) and women (HR = 1.78; 95% CI 1.23-2.57). This positive association was consistent across all five ethnicities. Former smokers had an elevated risk among men, but not among women. There was a significant trend by intensity (cigarettes per day) and duration (years) of smoking among all current smokers. After separation by anatomic location of their tumor, ever smokers had a higher risk for gastric cardia cancer (HR = 2.86; 95% CI 1.66-4.93) than for distal gastric cancer (HR = 1.52; 95% CI 1.25-1.86) among men and women combined. Analysis by histologic tumor type showed a stronger association between current smoking and the intestinal type. CONCLUSIONS: Overall, this study shows an association of current cigarette smoking with gastric cancer in both sexes, consistency of this effect across five ethnic groups, evidence for a dose-response effect of smoking in both sexes, a stronger effect for cardia than for distal gastric cancer, and a stronger association for intestinal than for diffuse gastric cancer. PMID- 22037907 TI - Factors associated with mortality after breast cancer metastasis. AB - BACKGROUND: It is generally accepted that patients with breast cancer metastases have very poor survival. Metastatic breast cancer patients can be considered a heterogeneous population with a varied clinical course, which underscores the need for accurate prediction of survival based on prognostic factors. The purpose of the present study was to identify factors related to survival in breast cancer patients after diagnosis with metastatic disease. POPULATIONS AND METHODS: A total of 557 patients with breast cancer metastasis diagnosis seen at one large urban practice have been followed up between 1 January, 1999 and 30 June, 2010. Demographic, tumor characteristics, clinical factors as predictors of survival were analyzed using log-rank test and Cox regression model. RESULTS: The median survival length was 39 months (range 1-138 months) with 154 (27.7%) alive and 403 (72.3%) dead at the end of follow-up period. This study demonstrated that a history of hypertension, ER/PR status, HER2 status, metastasis-free interval, metastatic location (including brain, bone and liver), and BMI at diagnosis with metastatic breast cancer were the most relevant prognostic factors for survival after metastatic disease diagnosis. CONCLUSION: Findings of this study may form a foundation for the growing corpus of knowledge explaining the outcome differences in treatment of patients with metastatic breast cancer, potentially helping to create tailored counseling and personalized treatment approaches for this vulnerable group. PMID- 22037908 TI - Hormone therapy and ovarian borderline tumors: a national cohort study. AB - PURPOSE: Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk. METHODS: A total of 909,875 Danish women 50-79 years old without previous hormone-sensitive cancers or bilateral oophorectomy were followed in this nationwide cohort study 1995-2005. The National Register of Medicinal Product Statistics provided exposure information on all women who redeemed prescriptions on hormone therapy. The National Cancer and Pathology Register provided data on borderline ovarian tumors. Information on confounding factors was available from other national registers. Poisson regression analyses provided risk estimates with hormone exposures as time dependent covariates. RESULTS: In an average of 8.0 years of follow-up, 703 incident ovarian borderline tumors were detected. Compared with never users, hormone use for more than 4 years increased the risk of borderline tumors: relative risk (RR) 1.40; 95% confidence interval (CI), 1.09-1.81. Combined estrogen and progestin therapy for more than 4 years increased the risk: RR 1.49 (1.10-2.01), with no difference between cyclic and continuous combined therapy (p = 0.83); RR 1.56 (1.08-2.25) and 1.45 (0.87-2.43), respectively. The RR with estrogen therapy did not differ significantly from RR with combined therapy (p = 0.58): RR 1.27 (0.82-1.98). Disregarding the type of hormone therapy, hormone use for 4 years or less did not increase the risk of borderline tumors. CONCLUSIONS: Combined hormone therapy for more than 4 years increases the risk of ovarian borderline tumors. PMID- 22037906 TI - Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium. AB - We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97). PMID- 22037909 TI - Occupational risks and lung cancer burden for Chinese men: a population-based case-referent study. AB - OBJECTIVE: We aimed to fill in the gap of knowledge on the lung cancer burden resulting from occupational exposures among Chinese men through a population based case-referent study. METHODS: Detailed information on lifestyle and full occupational histories of 1,208 male lung cancer incident cases and 1,069 age matched male community referents were obtained through interviews during 2004 2006. The associations between lung cancer risk and exposures to specific or group of agents that were confirmed or suspected occupational carcinogens were analyzed. RESULTS: After adjustment of smoking and other potential confounding factors, significant odds ratio of lung cancer was observed for workers employed in major industrial divisions of "construction" (1.37, 95% CI: 1.00-1.89) and "financing, insurance, real estate, and business services" (0.48, 95% CI: 0.23 0.97), as well as in the occupational groups of "bricklayers, carpenters, and other construction workers" (1.49, 95% CI: 1.07-2.06). Significantly elevated odds ratios were found for occupational exposures to silica dust (1.75, 95% CI: 1.16-2.62), welding fumes (1.74, 95% CI: 1.13-2.68), diesel exhaust (2.18, 95% CI: 1.23-3.84), and man-made mineral fibers (7.45, 95% CI: 1.63-34.00), while a significantly reduced risk (OR = 0.67, 95% CI: 0.47-0.95) was linked to cotton dust. The population attributable fraction of lung cancer was 3.2% (95% CI: 0.1 7.3%) for construction workers and 9.5% (95% CI: 4.8-15.1%) for the four significant specific exposures. CONCLUSIONS: Our study indicates that previous exposure to occupational carcinogens remains an important determinant of lung cancer burden for Hong Kong Chinese men. However, results obtained from this study should be confirmed by future analyses based on job exposure matrix. PMID- 22037910 TI - Manipulations of spinal cord excitability evoke developmentally-dependent compensatory changes in the lamprey spinal cord. AB - We have examined homeostatic or compensatory plasticity evoked by tonic changes in spinal cord excitability in the lamprey, a model system for investigating spinal cord function. In larval animals, reducing excitability by incubating in tetrodotoxin or the glutamate receptor antagonists CNQX or CNQX/AP5 for 20-48 h resulted in a diverse set of cellular and synaptic changes that together were consistent with an increase in spinal cord excitability. Similar changes occurred to a tonic increase in excitation evoked by incubating in high potassium physiological solution (i.e. responses were unidirectional). We also examined developmental influences on these effects. In animals developing from the larval to adult form effects were reduced or absent, suggesting that at this stage the spinal cord was more tolerant of changes in activity levels. Responses had returned in adult animals, but they were now bi-directional (i.e. opposite effects were evoked by an increase or decrease in excitability). The spinal cord can thus monitor and adapt cellular and synaptic properties to tonic changes in excitability levels. This should be considered in analyses of spinal cord plasticity and injury. PMID- 22037912 TI - Tail position affects the body temperature of rats during cold exposure in a low energy state. AB - Rats place their tails underneath their body trunks when cold (tail-hiding behavior). The aim of the present study was to determine whether this behavior is necessary to maintain body temperature. Male Wistar rats were divided into 'fed' and '42-h fasting' groups. A one-piece tail holder (8.4 cm in length) that prevented the tail-hiding behavior or a three-piece tail holder (2.8 cm in length) that allowed for the tail-hiding behavior was attached to the tails of the rats. The rats were exposed to 27 degrees C for 180 min or to 20 degrees C for 90 min followed by 15 degrees C for 90 min with continuous body temperature and oxygen consumption measurements. Body temperature decreased by -1.0 +/- 0.1 degrees C at 15 degrees C only in the rats that prevented tail-hiding behavior of the 42-h fasting group, and oxygen consumption increased at 15 degrees C in all animals. Oxygen consumption was not different between the rats that prevented tail-hiding behavior and the rats that allowed the behavior in the fed and 42-h fasting groups under ambient conditions. These results show that the tail-hiding behavior is involved in thermoregulation in the cold in fasting rats. PMID- 22037913 TI - Specialized brain regions and sensory inputs that control locomotion in leeches. AB - Locomotor systems are often controlled by specialized cephalic neurons and undergo modulation by sensory inputs. In many species, dedicated brain regions initiate and maintain behavior and set the duration and frequency of the locomotor episode. In the leech, removing the entire head brain enhances swimming, but the individual roles of its components, the supra- and subesophageal ganglia, in the control of locomotion are unknown. Here we describe the influence of these two structures and that of the tail brain on rhythmic swimming in isolated nerve cord preparations and in nearly intact leeches suspended in an aqueous, "swim-enhancing" environment. We found that, in isolated preparations, swim episode duration and swim burst frequency are greatly increased when the supraesophageal ganglion is removed, but the subesophageal ganglion is intact. The prolonged swim durations observed with the anterior-most ganglion removed were abolished by removal of the tail ganglion. Experiments on the nearly intact leeches show that, in these preparations, the subesophageal ganglion acts to decrease cycle period but, unexpectedly, also decreases swim duration. These results suggest that the supraesophageal ganglion is the primary structure that constrains leech swimming; however, the control of swim duration in the leech is complex, especially in the intact animal. PMID- 22037914 TI - 'Null method' determination of drug biophase concentration. AB - PK/PD modeling is enhanced by improvements in the accuracy of its metrics. For PK/PD modeling of drugs and biologics that interact with enzymes or receptors, the equilibrium constant of the interaction can provide critical insight. Methodologies such as radioliogand binding and isolated tissue preparations can provide estimates of the equilibrium constants (as the dissociation constant, K value) for drugs and endogenous ligands that interact with specific enzymes and receptors. However, an impediment to further precision for PK/PD modeling is that it remains a problem to convert the concentration of drug in bulk solution (A) into an estimate of receptor occupation, since A is not necessarily the concentration (C) of drug in the biophase that yields fractional binding from the law of mass action, viz., C/(C + K). In most experimental studies A is much larger than K, so the use of administered instead of biophase concentration gives fractional occupancies very close to unity. We here provide a simple way to obtain an estimate of the factor that converts the total drug concentration into the biophase concentration in isolated tissue preparation. Our approach is an extension of the now classic 'null method' introduced and applied by Furchgott to determination of drug-receptor dissociation constants. PMID- 22037916 TI - Mitral valve annuloplasty: a quantitative clinical and mechanical comparison of different annuloplasty devices. AB - Mitral valve annuloplasty is a common surgical technique used in the repair of a leaking valve by implanting an annuloplasty device. To enhance repair durability, these devices are designed to increase leaflet coaptation, while preserving the native annular shape and motion; however, the precise impact of device implantation on annular deformation, strain, and curvature is unknown. In this article, we quantify how three frequently used devices significantly impair native annular dynamics. In controlled in vivo experiments, we surgically implanted 11 flexible-incomplete, 11 semi-rigid-complete, and 12 rigid-complete devices around the mitral annuli of 34 sheep, each tagged with 16 equally spaced tantalum markers. We recorded four-dimensional marker coordinates using biplane videofluoroscopy, first with device and then without, which were used to create mathematical models using piecewise cubic splines. Clinical metrics (characteristic anatomical distances) revealed significant global reduction in annular dynamics upon device implantation. Mechanical metrics (strain and curvature fields) explained this reduction via a local loss of anterior dilation and posterior contraction. Overall, all three devices unfavorably caused reduction in annular dynamics. The flexible-incomplete device, however, preserved native annular dynamics to a larger extent than the complete devices. Heterogeneous strain and curvature profiles suggest the need for heterogeneous support, which may spawn more rational design of annuloplasty devices using design concepts of functionally graded materials. PMID- 22037917 TI - Lung metastases in metastatic gastric cancer: pattern of lung metastases and clinical outcome. AB - BACKGROUND: There are only limited data regarding pulmonary metastasis from gastric cancer. Therefore, we analyzed large series of gastric cancer with pulmonary metastasis and analyzed their clinical characteristics and treatment outcome to enhance perception of metastatic gastric cancer. METHODS: Of 20,187 advanced gastric cancer patients treated between 1995 and 2007, 193 (0.96%) were identified to have pulmonary metastasis from gastric cancer. The pulmonary lesions were detected at chest computed tomography (CT) scan or plain chest X-ray and/or abdominal pelvic CT scan covering the lower part of the lungs, and were divided into three patterns: lymphangitic, hematogenous, and pleural. RESULTS: The most frequently observed pattern of lung metastasis was hematogenous metastasis (52.3%) followed by pleural (35.2%) and lymphangitic (26.4%). Patients who had hematogenous pulmonary metastasis were significantly associated with hepatic metastasis (p = 0.004) and male sex (p = 0.012). Patients with lymphangitic metastasis were significantly associated with concomitant bone (p = 0.010) and bone marrow (p = 0.029) metastasis. In case of pleural metastasis, it was positively correlated with gastrectomy history (p = 0.015) and the presence of peritoneal metastasis (p = 0.020). After a median follow-up duration of 87 (9 162) months, the median survival after diagnosis of pulmonary metastasis was 4 (0 67) months. CONCLUSION: The most frequently observed pattern of lung metastasis was hematogenous metastasis (52.3%) followed by pleural (35.2%) and lymphangitic (26.4%) in gastric cancer patients. Among gastric cancer patients with lung metastases, patients with pleural metastasis or lymphangitic metastasis had shorter survival with 1.5-2-fold increased risk of deaths. PMID- 22037918 TI - Who's funny: gender stereotypes, humor production, and memory bias. AB - It has often been asserted, by both men and women, that men are funnier. We explored two possible explanations for such a view, first testing whether men, when instructed to be as funny as possible, write funnier cartoon captions than do women, and second examining whether there is a tendency to falsely remember funny things as having been produced by men. A total of 32 participants, half from each gender, wrote captions for 20 cartoons. Raters then indicated the humor success of these captions. Raters of both genders found the captions written by males funnier, though this preference was significantly stronger among the male raters. In the second experiment, male and female participants were presented with the funniest and least funny captions from the first experiment, along with the caption author's gender. On a memory test, both females and males disproportionately misattributed the humorous captions to males and the nonhumorous captions to females. Men might think men are funnier because they actually find them so, but though women rated the captions written by males slightly higher, our data suggest that they may regard men as funnier more because they falsely attribute funny things to them. PMID- 22037919 TI - Enhancing visuospatial performance through video game training to increase learning in visuospatial science domains. AB - Although previous research has demonstrated that performance on visuospatial assessments can be enhanced through relevant experience, an unaddressed question is whether such experience also produces a similar increase in target domains (such as science learning) where visuospatial abilities are directly relevant for performance. In the present study, participants completed either spatial or nonspatial training via interaction with video games and were then asked to read and learn about the geologic topic of plate tectonics. Results replicate the benefit of playing appropriate video games in enhancing visuospatial performance and demonstrate that this facilitation also manifests itself in learning science topics that are visuospatial in nature. This novel result suggests that visuospatial training not only can impact performance on measures of spatial functioning, but also can affect performance in content areas in which these abilities are utilized. PMID- 22037920 TI - Changes of cortico-muscular coherence: an early marker of healthy aging? AB - Cortico-muscular coherence (CMC) at beta frequency (13-30 Hz) occurs particularly during weak to moderate isometric contraction. It is a well-established measure of communication between the primary motor cortex (M1) and corresponding muscles revealing information about the integrity of the pyramidal system. Although the slowing of brain and muscle dynamics during healthy aging has been evidenced, functional communication as determined by CMC has not been investigated so far. Since decline of motor functions at higher age is likely to be associated with CMC changes, the present study aims at shedding light on the functionality of the motor system from a functional interaction perspective. To this end, CMC was investigated in 27 healthy subjects aging between 22 and 77 years during isometric contraction of their right forearm. Neuromagnetic activity was measured using whole-head magnetoencephalography (MEG). Muscle activity was measured by means of surface electromyography (EMG) of the right extensor digitorum communis (EDC) muscle. Additionally, MEG-EMG phase lags were calculated in order to estimate conducting time. The analysis revealed CMC and M1 power amplitudes to be increased with age accompanied by slowing of M1, EMG, and CMC. Frequency changes were particularly found in subjects aged above 40 years suggesting that at this middle age, neurophysiological changes occur, possibly reflecting an early neurophysiological marker of seniority. Since MEG-EMG phase lags did not vary with age, changes cannot be explained by alterations of nerve conduction. We argue that the M1 power amplitude increase and the shift towards lower frequencies might represent a neurophysiological marker of healthy aging which is possibly compensated by increased CMC amplitude. PMID- 22037921 TI - Intimate partner violence and mental health effects: a population-based study among married women in Karachi, Pakistan. AB - BACKGROUND: Intimate partner violence (IPV) is recognized all over the world for its association with mental health problems in women. In Pakistan, such violence occurs commonly, but detailed information on mental health effects is scarce. The purpose of this study is to focused on married couples in urban Karachi to investigate mental health effects associated with physical, sexual and psychological violence perpetrated by husbands towards wives. Disclosure rates and health care-seeking behaviour were also investigated. METHOD: This cross sectional study involved 759 women between the ages of 25 and 60 years, selected using a multi-stage random sampling technique. The women were interviewed by trained community midwives using a structured questionnaire. RESULTS: In the total population of women, mental symptoms were prevalent. Women subjected to any form of violence reported, however, considerably poorer mental health than unexposed women. A statistically significant difference for almost all of the studied health parameters persisted even after controlling for socio-demographic factors. The strongest associations were found for suicidal thoughts and physical violence (OR 4.41; 3.18-6.12), sexual abuse (OR 4.39; 3.17-6.07) and psychological abuse (OR 5.17; 3.28-8.15). The interviews revealed that only 27% of the women subjected to violence had disclosed this to anyone, in most cases to their parents. CONCLUSION: The findings in this study highlight that the violence women have to face contributes to the development of multiple forms of psychological stress and serious mental health problems. Women's restrictive life circumstances seriously hamper women's empowerment. Reliable health surveillance system and health care services are needed to serve abused women. Policy initiatives focused on IPV and gender inequality in Pakistan should be initiated. PMID- 22037922 TI - Feasibility of biweekly combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in patients with metastatic solid tumors: results of a two-step phase I trial: XELIRI and XELIRINOX. AB - BACKGROUND: Biweekly schedule of capecitabine combined with irinotecan (XELIRI), consecutively with irinotecan and oxaliplatin (XELIRINOX), was evaluated in patients with metastatic cancer from any solid tumors. PATIENTS AND METHODS: In this two-step phase I trial, seventeen and eleven patients were enrolled in the XELIRI and XELIRINOX stages, respectively. RESULTS: In XELIRI, a total of 136 chemotherapy cycles were administered with a median number of 8 cycles per patient (2-16). Main dose-limiting toxicities (DLT) were grade 3-4 neutropenia, with one toxicity-related death. Maximum tolerated dose (MTD) for capecitabine combined with 180 mg/m(2) of irinotecan was 3,500 mg/m(2)/day. In XELIRINOX, capecitabine starting dose was 2,500 mg/m(2)/day. Fifty-eight chemotherapy cycles were administered with a median of 4 cycles per patient (1-16). DLT included 3 grade 4 neutropenia, associated with 1 grade 3 diarrhea, and 1 grade 4 pneumopathy leading to patient death. MTD for capecitabine with 180 mg/m(2) of irinotecan and 85 mg/m(2) of oxaliplatin was 3,000 mg/m(2)/day. The recommended doses for capecitabine were 3,000 and 2,500 mg/m(2)/day D1-D7 in combination with 180 mg/m(2) of irinotecan in XELIRI, plus 85 mg/m(2) of oxaliplatin in XELIRINOX (D1 = D14), respectively. CONCLUSION: XELIRI and XELIRINOX regimens are feasible and warrant further investigation in combination with targeted therapy in metastatic colorectal cancer patients. PMID- 22037923 TI - Ridaforolimus for patients with progressive or recurrent malignant glioma: a perisurgical, sequential, ascending-dose trial. AB - PURPOSE: This perisurgical phase 1 study evaluated the pharmacokinetics, pharmacodynamics, and safety of the mammalian target of rapamycin (mTOR) inhibitor ridaforolimus in patients (N = 10) with progressive or recurrent primary grade IV malignant glioma, who failed standard therapy. The primary objective of the study was to determine the maximum tolerated dose (MTD) of ridaforolimus. METHODS: Treatment was administered intravenously at doses of 12.5 mg (N = 7) or 15 mg (N = 3) once daily for 4 days prior to surgical resection, then resumed for 5 consecutive days every 2 weeks until disease progression or unacceptable toxicity, following a postsurgical recovery period. RESULTS: The MTD was not determined because the trial was suspended early due to slower than expected patient accrual and postsurgical drug administration challenges. Pharmacokinetic and pharmacodynamic analyses showed that ridaforolimus concentrations declined slowly during the 24-h dosing interval and remained detectable for 10 days after the last infusion in whole blood samples. In peripheral blood mononuclear cells, median levels of the mTOR downstream effector p4E-BP1 were reduced by >80% compared with baseline by 4 h after dosing. Resected brain specimens showed reduced levels of pS6, another mTOR downstream effector, while nuclear staining for p27(kip1), a protein that functions as a cell cycle inhibitor, increased after treatment. No dose-limiting toxicities were observed, and the reported adverse events were consistent with the previously established safety profile for ridaforolimus. One of 3 patients evaluable for efficacy had stable disease as best response. CONCLUSION: Results suggest that ridaforolimus can cross the blood-brain barrier in areas of tumor involvement, and may inhibit mTOR activity in advanced gliomas based on decreased pS6 levels. This perisurgical trial design should serve as a template for evaluating intratumoral pharmacokinetics and pharmacodynamics of other targeted agents in this patient population. PMID- 22037924 TI - The role of lapatinib in the preoperative therapy of breast cancer. AB - Preoperative or neoadjuvant chemotherapy is a well-established modality in the treatment of nonmetastatic breast cancer. Patients initially considered inoperable may be able to achieve operable status after preoperative chemotherapy and patients initially considered not to be candidates for breast conservation may convert to breast conservation status. Human epidermal growth factor receptor 2 (Her2)-positive tumors have been shown to have a more aggressive course including early local relapse and metastasis when compared to Her2-negative breast cancers, but the optimal use of Her2-targeted agents is constantly evolving as new agents become available. Preoperative studies allow us to quickly assess the activity of new agents and combinations for particular biological subsets of breast cancer. PMID- 22037925 TI - Involvement of PI3K, GSK-3beta and PPARgamma in the antidepressant-like effect of folic acid in the forced swimming test in mice. AB - Preclinical and clinical studies indicate that deficiency in folic acid plays a role in the pathophysiology of depression. Considering that alterations in the signaling pathways that regulate neuroplasticity and cellular survival are implicated in depressive disorders, the present study investigated the involvement of the phosphoinositide 3-kinase (PI3K), glycogen synthase kinase-3 (GSK-3beta), and peroxisome proliferator-activated receptor-gamma (PPARgamma) in the antidepressant-like effect of folic acid in the forced swimming test (FST). The intracerebroventricular (i.c.v.) pre-treatment of mice with LY294002 (10 nmol/site, a PI3K inhibitor) or GW-9662 (1 ug/site, a PPARgamma antagonist) prevented the antidepressant-like effect of folic acid (50 mg/kg, p.o.) in the FST. In addition, the administration of subeffective doses of the selective GSK 3beta inhibitor, AR-A014418 (3 mg/kg, i.p.), a non-selective GSK-3beta inhibitor, lithium chloride (10 mg/kg, p.o) or a PPARgamma agonist, rosiglitazone (1 ug/site, i.c.v.) in combination with a subeffective dose of folic acid (10 mg/kg, p.o.) significantly reduced the immobility time in the FST as compared with either drug alone, without altering the locomotor activity. These results indicate that the antidepressant-like effect of folic acid in the FST might be dependent on inhibition of GSK-3beta and activation of PPARgamma, reinforcing the notion that these are important targets for antidepressant activity. PMID- 22037926 TI - Effects of production intensity and production strategies in commercial Atlantic salmon smolt (Salmo salar L.) production on subsequent performance in the early sea stage. AB - A data set from commercial Atlantic salmon (Salmo salar L.) producers on production intensity and production strategies in smolt tanks (N = 63-94) was obtained during 1999-2006. The effects of production intensity on subsequent fish mortality and growth during the early sea phase (90 days) were examined by principal component analysis and subsequent generalized linear model analysis. Levels of accumulated metabolites (CO(2), total ammonia nitrogen and NH(3)), and information provided by producers (production density (kg fish m(3-1)), specific water use (l kg fish(-1) min(-1)) and oxygen drop (mg l(-1)) from tank inlet to tank outlet), were used as predictor variables. In addition, several other welfare relevant variables such as disease history, temperature during freshwater and sea stage; season (S1) or off-season (S0) smolt production; and the use of seawater addition during the freshwater stage were analyzed. No strong intensity effects on mortality or growth were found. CO(2) levels alone (P < 0.001, R(2) = 0.16), and in combination with specific water use (R(2) = 0.20), had the strongest effect on mortality. In both cases, mortality decreased with increasing density. For growth, the intensity model with the most support (R(2) = 0.17) was O(2) drop, density and their interaction effects, resulting in the best growth at low and high intensity, and poorer growth at intermediate levels. Documented viral disease outbreaks (infectious pancreatic necrosis and two cases of pancreas disease) in the sea phase resulted in significantly higher mortalities at 90 days compared with undiagnosed smolt groups, although mortalities were highly variable in both categories. The temperature difference between the freshwater stage and seawater had a small, but significant, effect on growth with the best growth in groups stocked to warmer seawater (P = 0.04, R(2) = 0.06). S0 and S1 smolt groups did not differ significantly in growth, but the mortality was significantly (P = 0.02) higher in S1 groups. Seawater addition as a categorical variable had no significant effects, but when analyzed within the seawater addition group, intermediate salinities (15-25 ppt) gave the best results on growth (p = 0.04, R(2) = 0.15). Production intensity had small explanatory power on subsequent seawater performance in the analyzed smolt groups. If anything, the analysis shows a beneficial effect of intensive production strategies on subsequent performance. Analysis of the various production strategies indicates better survival of S0 compared with S1 smolt groups, improved growth when stocked in seawater warmer than freshwater, and a negative effect of viral disease outbreaks on survival. The results clearly demonstrate the difficulty of extrapolating results from experimental work on fish welfare and production intensity variables to commercial production. On the other hand, the presented results may simply demonstrate that the traditional fish welfare criteria growth and mortality may not suffice to evaluate welfare consequences of suboptimal water quality or production strategies in the aquaculture industry. PMID- 22037927 TI - [Inferior vestibular neuritis: diagnosis using VEMP]. AB - Vestibular evoked myogenic potentials (VEMP) are a new method to establish the functional status of the otolith organs. The sacculocollic reflex of the cervical VEMP to air conduction (AC) reflects predominantly saccular function due to saccular afferents to the inferior vestibular nerve. We describe a case of inferior vestibular neuritis as a rare differential diagnosis of vestibular neuritis. Clinical signs were a normal caloric response, unilaterally absent AC cVEMPs and bilaterally preserved ocular VEMPs (AC oVEMPs). PMID- 22037928 TI - [Idiopathic facial palsy during pregnancy]. AB - BACKGROUND: Idiopathic facial (Bell's) palsy occurring during pregnancy or post partum is a rare disease. Reports regarding incidence, prognosis and associated risk factors are still inconsistent. MATERIAL AND METHODS: We performed a retrospective analysis of patients presenting with idiopathic facial palsy who had been treated in cooperation between obstetric and otorhinolaryngological departments (tertiary referral centers). The time of onset of paralysis, grading according to House and Brackman, treatment modalities and results were analyzed for the years 1999-2010. RESULTS: The incidence of Bell's palsy in pregnancy was 56 in 100,000 live births. Preeclampsia was reported in one case only. Therapy included prednisolone, methylprednisolone and/or pentoxifylline (up to 2005). All results were favorable (House-Brackman 1-2). CONCLUSION: The incidence of Bell's palsy in pregnancy within our cohort is not increased with regard to the international reports. Early treatment with corticosteroids in consultation with the treating obstetrician is indicated in both pregnant and post-partum patients to achieve optimal results. PMID- 22037929 TI - [Psychometric instruments for the diagnosis of tinnitus]. AB - Tinnitus is a very complex phenomenon with various mechanisms of origin. Multimodal and interdisciplinary treatment is the most effective form of treatment for patients with chronic tinnitus. In order to assess existing comorbidity in tinnitus patients as well as to treat the patients individually, a comprehensive and differentiated diagnosis is needed. Since standardized guidelines for the use of relevant instruments in the diagnosis of tinnitus have been lacking hitherto, we present here psychometric questionnaires which have already been used effectively in the research, diagnosis and therapy of tinnitus in the present article. The questionnaires measure the severity of tinnitus, depression and anxiety, the perceived stress, personal resources as well as the quality of life of patients. PMID- 22037930 TI - Precervical myositis ossificans in an infant secondary to child abuse. AB - We present a 10-week-old girl with myositis ossificans circumscripta (MO) of the neck secondary to nonaccidental trauma. This condition is rarely seen in infants; furthermore, the majority of MO lesions develop in the extremities rather than the head and neck region. We will detail the US-guided biopsy technique used in our case, in addition to discussing the characteristic imaging and pathological findings of MO to assist in the diagnosis and successful treatment of this condition. PMID- 22037931 TI - Pre- and postoperative imaging and interventions for the meso-Rex bypass in children and young adults. AB - The meso-Rex bypass is a physiological and anatomical bypass procedure for relief of extrahepatic portal vein obstruction and restoration of mesenteric venous return to the liver. Most patients who are candidates for the bypass are children or young adults with portal hypertension and hypersplenism secondary to cavernous transformation of the portal vein. Most frequently, the bypass utilizes an autologous venous graft to connect the intrahepatic left portal vein to the infrapancreatic superior mesenteric vein (SMV) re-establishing first-pass portal perfusion. We describe the preoperative imaging of the 92 bypass candidates, the surgical anatomy as reflected in postoperative imaging, and the imaging of bypass complications at our institution.Preoperative imaging with US, CT and MR is directed to demonstrate patency and size of the left portal vein and SMV, to define the extent of cavernous transformation and splanchnic collaterals, and to assess for any associated abdominal vascular or solid organ abnormalities. Postoperative imaging is aimed at diagnosing meso-Rex bypass stenosis or occlusion and the interventional management of these complications. PMID- 22037932 TI - Fetal demise on MRI. PMID- 22037934 TI - Impact of FDG-PET/CT in the management of lymphoma. AB - Since the introduction of (67)Gallium-citrate 30 years ago, nuclear medicine has played an important role in the evaluation of malignant lymphoma. During that time, several radiotracers were evaluated as potential alternatives for the diagnosis of lymphoma, but the introduction of (18)F-fluorodeoxyglucose PET (FDG PET) marked a major turning point. FDG-PET took over most of the role of gallium, and is now an essential tool in the diagnosis of lymphoma. FDG-PET is increasingly being used for assessment of the tumor staging prior to treatment, for evaluating the response to treatment, and for monitoring the early reactions to therapy to predict the final outcome. FDG-PET has been shown to have more accurate diagnostic capability than conventional CT and MRI for distinguishing the tumor necrosis and residual masses frequently seen after therapy in lymphoma patients without any clinical and biochemical manifestation. Malignant lymphoma is the first disease for which FDG-PET was adopted as a tool for response assessment in the international standard criteria. However, lymphoma does not always display a clear high uptake, and there are some pitfalls in assessing the response to therapy. This review will highlight the most important applications of FDG-PET in lymphoma, focusing on the advantages and pitfalls of this imaging, and past and ongoing efforts to standardize the use of FDG-PET, particularly in response to assessment and therapy monitoring. PMID- 22037935 TI - Reclassification of SIDS cases--a need for adjustment of the San Diego classification? AB - A study was undertaken reclassifying cases of sudden infant death syndrome (SIDS) taken from two geographically separate locations utilizing the San Diego definition with subclassifications. One hundred twenty-eight infant cases were examined from files at Forensic Science South Australia in Adelaide, SA, Australia over a 7.5-year period from July 1999 to January 2007. Thirty-one cases (24%) had initially been diagnosed as SIDS and 30 (23%) as undetermined while 67 (52%) had an explainable cause of death. After reclassification, the number of SIDS cases had increased to 49 of the 128 cases, now representing 38% of the cases; category IB SIDS constituted 10 (20%) and II SIDS 39 (80%) of the SIDS cases. No cases were classified as IA SIDS. Two hundred eighteen infant cases were identified from the files of the Department of Forensic Medicine, Aarhus University, Denmark over a 16-year period from 1992 to 2007. Eighty-two (38%) were originally diagnosed as SIDS, 128 (59%) with identifiable causes of death, and 8 (4%) as unexplained. After review, 77 (35%) cases were reclassified as SIDS, a decrease of 6%. Twenty (26%) infants were classified as category IB SIDS and 57 (74%) as II SIDS. None of the cases met the criteria for IA SIDS. Problems arose in assessing cases with failure to thrive, fever, and possible asphyxia. Modifications to the San Diego subclassifications might improve the consistency of categorizing these cases. PMID- 22037937 TI - Synthesis and characterization of a template-assembled synthetic U-quartet. AB - A lipophilic cavitand containing four triazole-linked uridine residues has been synthesized and characterized. Spectral evidence suggests a quartet arrangement of the uracil residues at both ambient and low temperatures. Treatment of the compound with Sr(2+) yields a homodimeric complex as evidenced by NMR spectroscopy. PMID- 22037936 TI - Neural correlates of pathological gamblers preference for immediate rewards during the iowa gambling task: an fMRI study. AB - The Iowa Gambling Task (IGT) involves exploratory learning via rewards and penalties, where most advantageous task performance requires subjects to forego potential large immediate rewards for small longer-term rewards to avoid larger punishments. Pathological gambling (PG) subjects perform worse on the IGT compared to controls, relating to their persistence at high risk decisions involving the continued choice of potential large immediate rewards despite experiencing larger punishments. We wished to determine if neural processing of risk and reward within striatal and frontal cortex is associated with this behaviour observed in PG. Functional magnetic resonance imaging (fMRI) was used to assess brain activity in response to a computerized version of the IGT. Thirteen male PG subjects with no active comorbidities were compared to 13 demographically matched control subjects. In agreement with previous behavioural studies, PG subjects performed worse on the IGT and made more high-risk choices compared to controls, particularly after experiencing wins and losses. During high-risk gambling decisions, fMRI demonstrated that PG subjects exhibited relatively increased frontal lobe and basal ganglia activation, particularly involving the orbitofrontal cortex (OFC), caudate and amygdala. Increased activation of regions encompassing the extended reward pathway in PG subjects during high risk choices suggests that the persistence of PG may be due to the increased salience of immediate and greater potential monetary rewards relative to lower monetary rewards or potential future losses. Whether this over activation of the reward pathway is associated with the development of PG warrants further investigation. PMID- 22037938 TI - Uterine prolapse complicating pregnancy and labor: a case report and literature review. AB - BACKGROUND: Uterine and cervical prolapse is a rare occurrence in pregnancy. It can be associated with minor cervical desiccation and ulceration to devastating maternal fatalities. The scope of complications includes urinary retention, preterm labor, premature delivery, fetal demise, maternal sepsis, and urinary retention. METHODS: We present a case of a lady, who developed uterine and cervical prolapse during pregnancy and the issues surrounding her antenatal and intrapartum management. RESULTS AND CONCLUSION: This case report highlights the effectiveness of a Gellhorn pessary for uterine prolapse in pregnancy. PMID- 22037939 TI - Postoperative tetanus after laparoscopic obturator hernia repair for strangulated ileus: report of a case. AB - This report presents the case of an 84-year-old woman who developed tetanus 3 days after the resection of a gangrenous small intestine caused by obturator hernia incarceration. The diagnosis of tetanus was clinically made after the appearance of generalized spastic contractions with opisthotonus. Clostridium tetani organisms residing in the gastrointestinal tract were presumed to have been endogenously inoculated into the strangulated intestine, where it produced tetanospasmin, causing tetanus. The patient successfully recovered after aggressive intensive care. There have been 16 case reports of tetanus occurring after gastrointestinal surgical procedures. Primary care physicians should thus be aware of the fact that, although extremely rare, C. tetani residing in the gastrointestinal tract can provide a possible endogenous source of tetanus infection. PMID- 22037941 TI - The thromboxane synthase and receptor signaling pathway in cancer: an emerging paradigm in cancer progression and metastasis. AB - Thromboxane A(2) (TXA(2)) is a biologically active metabolite of arachidonic acid formed by the action of the terminal synthase, thromboxane A(2) synthase (TXA(2)S), on prostaglandin endoperoxide (PGH(2)). TXA(2) is responsible for multiple biological processes through its cell surface receptor, the T-prostanoid (TP) receptor. Thromboxane A(2) synthase and TP are the two necessary components for the functioning of this potent bioactive lipid. Thromboxane A(2) is widely implicated in a range of cardiovascular diseases, owing to its acute and chronic effects in promoting platelet aggregation, vasoconstriction, and proliferation. In recent years, additional functional roles for both TXA(2)S and TP in cancer progression have been indicated. Increased cyclooxygenase (COX)-2 expression has been described in a variety of human cancers, which has focused attention on TXA(2) as a downstream metabolite of the COX-2-derived PGH(2). Several studies suggest potential involvement of TXA(2)S and TP in tumor progression, especially tumor cell proliferation, migration, and invasion that are key steps in cancer progression. In addition, the regulation of neovascularization by TP has been identified as a potent source of control during oncogenesis. There have been several recent reviews of TXA(2)S and TP but thus far none have discussed its role in cancer progression and metastasis in depth. This review will focus on some of the more recent findings and advances with a significant emphasis on understanding the functional role of TXA(2)S and TP in cancer progression and metastasis. PMID- 22037944 TI - Strategies for improving documentation and reducing medication errors related to drug allergy. AB - New technologies like computerized physician order entry systems, that includes a support alert for drug allergies, can be an effective tool to prevent medical errors related to drug hypersensitivity most of them caused by lack of documentation and information. PMID- 22037942 TI - Dissecting the role of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in colon, breast, and lung carcinogenesis. AB - Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) is a promising drug target since its agonists increase serum high-density lipoprotein; decrease low-density lipoprotein, triglycerides, and insulin associated with metabolic syndrome; improve insulin sensitivity; and decrease high fat diet induced obesity. PPARbeta/delta agonists also promote terminal differentiation and elicit anti-inflammatory activities in many cell types. However, it remains to be determined whether PPARbeta/delta agonists can be developed as therapeutics because there are reports showing either pro- or anti-carcinogenic effects of PPARbeta/delta in cancer models. This review examines studies reporting the role of PPARbeta/delta in colon, breast, and lung cancers. The prevailing evidence would suggest that targeting PPARbeta/delta is not only safe but could have anti carcinogenic protective effects. PMID- 22037943 TI - 15-Lipoxygenase-1 as a tumor suppressor gene in colon cancer: is the verdict in? AB - 15-Lipoxygenase-1 (15-LOX-1) is an inducible and highly regulated enzyme in normal human cells that plays a key role in the production of lipid signaling mediators, such as 13-hydroxyoctadecadienoic acid (13-HODE) from linoleic acid. 15-LOX-1 significantly contributes to the resolution of inflammation and to the terminal differentiation of normal cells. 15-LOX-1 is downregulated in human colorectal polyps and cancers. Emerging data support a tumor suppressor role for 15-LOX-1, especially in colon cancer. These data indicate that 15-LOX-1 promotes various anti-tumorigenic events, including cell differentiation and apoptosis, and inhibits chronic inflammation, angiogenesis, and metastasis. The transcriptional repression of 15-LOX-1 in colon cancer cells is complex and involves multiple mechanisms (e.g., histone methylation, transcriptional repressor binding). Re-expression of 15-LOX-1 in colon cancer cells can function as an important therapeutic mechanism and could be further exploited to develop novel treatment approaches for this common cancer. PMID- 22037945 TI - Changes in cardiac structure and function in rats immunized by angiotensin type 1 receptor peptides. AB - Angiotensin II (Ang II) is known to induce cardiomyocyte hypertrophy by activating the Ang II type 1 (AT1) receptor. Some studies have demonstrated that the autoantibodies against angiotensin AT1 receptor (AT1-AAs) cause functional effects, which is similar to those observed for the natural agonist Ang II. In this study, we investigated the effects of AT1-AAs on cardiomyocytes' structure and function. Male Wistar rats were immunized with synthetic peptides corresponding to the second extracellular loop of AT1 receptor and Freund's adjuvant. The titers of AT1-AAs in rat serum were detected by enzyme-linked immunosorbent assay every week. Hemodynamic analysis and heart weight (HW) indices were measured on the 4th and 8th months after initial immunization, respectively. Cultured neonatal rat cardiomyocytes were used to observe the hypertrophic effects of AT1-AAs. Results showed that systolic blood pressure and heart rate were significantly increased, the titers of AT1-AAs were also increased after 4 weeks of initial immunization. Compared with control group, the HW/body weight (BW) and left ventricular weight/BW of immunized rats were increased significantly and cardiac function was enhanced compensatively. The cultured neonatal rat cardiomyocytes respond to AT1-AAs stimulation with increased (3)H-leucine incorporation and cell surface area in a dose-dependent manner. These results suggest that the AT1-AAs have an agonist effect similar to Ang II in hypertrophy of cardiomyocytes in vivo and in vitro. AT1-AAs are involved in the pathogenesis of cardiovascular diseases and hypertension. PMID- 22037946 TI - Identification of succinic semialdehyde reductases from Geobacter: expression, purification, crystallization, preliminary functional, and crystallographic analysis. AB - Succinic semialdehyde reductase (SSAR) is an important enzyme involved in gamma aminobutyrate (GABA) metabolism. By converting succinic semialdehyde (SSA) to gamma-hydroxybutyrate (GHB), the SSAR facilitates an alternative pathway for GABA degradation. In this study, we identified SSARs from Geobacter sulfurreducens and Geobacter metallireducens (GsSSAR and GmSSAR, respectively). The enzymes were over-expressed in Escherichia coli and purified to near homogeneity. Both GsSSAR and GmSSAR showed the activity of reducing SSA using nicotinamide adenine dinucleotide phosphate as a co-factor. The oligomeric sizes of GsSSAR and GmSSAR, as determined by analytical size exclusion chromatography, suggest that the enzymes presumably exist as tetramers in solution. The recombinant GsSSAR and GmSSAR crystallized in the presence of NADP(+), and the resulting crystals diffracted to 1.89 A (GsSSAR) and 2.25 A (GmSSAR) resolution. The GsSSAR and GmSSAR crystals belong to the space groups P2(1)22(1) (a= 99.61 A, b= 147.49 A, c= 182.47 A) and P1 (a= 75.97 A, b= 79.14 A, c= 95.47 A, alpha = 82.15 degrees , beta = 88.80 degrees , gamma = 87.66 degrees ), respectively. Preliminary crystallographic data analysis suggests the presence of eight protein monomers in the asymmetric units for both GsSSAR and GmSSAR. PMID- 22037947 TI - Fibrinogen as a key regulator of inflammation in disease. AB - The interaction of coagulation factors with the perivascular environment affects the development of disease in ways that extend beyond their traditional roles in the acute hemostatic cascade. Key molecular players of the coagulation cascade like tissue factor, thrombin, and fibrinogen are epidemiologically and mechanistically linked with diseases with an inflammatory component. Moreover, the identification of novel molecular mechanisms linking coagulation and inflammation has highlighted factors of the coagulation cascade as new targets for therapeutic intervention in a wide range of inflammatory human diseases. In particular, a proinflammatory role for fibrinogen has been reported in vascular wall disease, stroke, spinal cord injury, brain trauma, multiple sclerosis, Alzheimer's disease, rheumatoid arthritis, bacterial infection, colitis, lung and kidney fibrosis, Duchenne muscular dystrophy, and several types of cancer. Genetic and pharmacologic studies have unraveled pivotal roles for fibrinogen in determining the extent of local or systemic inflammation. As cellular and molecular mechanisms for fibrinogen functions in tissues are identified, the role of fibrinogen is evolving from a marker of vascular rapture to a multi-faceted signaling molecule with a wide spectrum of functions that can tip the balance between hemostasis and thrombosis, coagulation and fibrosis, protection from infection and extensive inflammation, and eventually life and death. This review will discuss some of the main molecular links between coagulation and inflammation and will focus on the role of fibrinogen in inflammatory disease highlighting its unique structural properties, cellular targets, and signal transduction pathways that make it a potent proinflammatory mediator and a potential therapeutic target. PMID- 22037950 TI - Stroke and Fabry disease. AB - Fabry disease (FD) is a rare inherited disorder of the metabolism, associated with renal, cardiac, and cerebrovascular complications. Ischemic and hemorrhagic stroke in FD present with a similar proportion to that observed in the general population, but usually at an early age. Ischemic stroke may result from cardiac embolism, large and small vessel disease, while hemorrhagic stroke is usually attributed to hypertension. Deposition of glycosphingolipids in endothelial cells results in a specific FD vasculopathy that contributes to the different vascular phenotypes. Neuroimaging features of cerebrovascular involvement in FD include white matter lesions, dolichoectasia, and the "pulvinar sign", a T1 MRI hyperintensity of the posterior thalamus. The role of enzymatic replacement therapy in the prevention of stroke remains to be established, but its utilization should be considered in FD stroke patients, for prevention of renal and cardiac complications, together with general prevention measures. Enzymatic replacement therapy increased our awareness of FD, underlining the importance of incomplete phenotypes in specific settings such as stroke. An overview of studies on the prevalence of FD in stroke patients is presented. Available data suggest that prevalence of FD is similar to some of the rare causes of stroke usually considered, and that classic features of the disease may be absent or more subtle. Moreover, FD should be considered in both cryptogenic and all-cause stroke. The role of FD in stroke on a multifactorial basis and the identification of a putative "stroke variant" are questions that need to be further elucidated in future studies. PMID- 22037951 TI - Stroke: new TIA definition, new anticoagulation, no stenting. PMID- 22037949 TI - Metabolic oligosaccharide engineering: implications for selectin-mediated adhesion and leukocyte extravasation. AB - Metabolic oligosaccharide engineering is an emerging technology wherein non natural monosaccharide analogs are exogenously supplied to living cells and are biosynthetically incorporated into cell surface glycans. A recently reported application of this methodology employs fluorinated analogs of ManNAc, GlcNAc, and GalNAc to modulate selectin-mediated adhesion associated with leukocyte extravasation and cancer cell metastasis. This monograph outlines possible mechanisms underlying the altered adhesion observed in analog-treated cells; these range from the most straightforward explanation (e.g., structural changes to the selectin ligands ablate interaction with their receptors) to the alternative mechanism where the analogs inhibit or otherwise perturb ligand production to more indirect mechanisms (e.g., changes to the biophysical properties of the selectin binding partner, the nanoenviroment of the binding partners, or the entire cell surface). PMID- 22037948 TI - Immunopathogenesis of Staphylococcus aureus pulmonary infection. AB - Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. Severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent USA300 CA-MRSA strains in the general population. The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. Its metabolic versatility, the ability to scavenge iron, coordinate gene expression, and the horizontal acquisition of useful genetic elements have all contributed to its success as a component of the respiratory flora, in hospitalized patients, as a complication of influenza and in normal hosts. The expression of surface adhesins facilitates its persistence in the airways. In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the alpha hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia. PMID- 22037953 TI - Judgment of FLAIR signal change in DWI-FLAIR mismatch determination is a challenge to clinicians. PMID- 22037954 TI - Perrault syndrome: further evidence for genetic heterogeneity. PMID- 22037956 TI - Hereditary neuropathy with liability to pressure palsy combined with suspected schwannomas of the peroneal and radial nerves. PMID- 22037955 TI - Recent advances in the diagnosis and treatment of balance disorders. AB - Here we summarize the recent progress made in the diagnosis and treatment of balance and gait disorders. Focusing on work published in the Journal of Neurology in 2010 and 2011, we have found evidence for the following clinically relevant statements: (1) the exclusion of stroke in acute vestibular syndromes is based on the bedside clinical findings; (2) the risk of developing secondary somatoform vertigo is predictable; it is especially high in patients with vestibular migraine; (3) postural imbalance and falls in Parkinson syndromes are related to dysfunction of the cholinergic midbrain thalamic axis; (4) aminopyridines improve a variety of cerebellar parameters including central nystagmus and gait variability. PMID- 22037957 TI - Pure left hippocampal stroke: a transient global amnesia-plus syndrome. PMID- 22037958 TI - Executive dysfunction in frontotemporal dementia is related to abnormalities in frontal white matter tracts. AB - Cognitive deficits in behavioral-variant frontotemporal dementia (bvFTD) and AD are linked to frontal and temporal lobe gray matter (GM) pathology. The aim of this study was to assess the relative contribution of white (WM) and GM abnormalities to cognitive dysfunction in bvFTD and AD. Fractional anisotropy (FA) for the corpus callosum, cingulum (Cg), and uncinate fasciculus (Unc) was determined in 17 bvFTD and 10 AD patients who underwent neuropsychological testing. Regressions were performed to assess the relative contribution of WM and GM abnormalities to cognitive deficits. Multiple regression analysis revealed that in bvFTD, the left anterior Cg FA was related to executive function, the right anterior Cg FA to visual-spatial attention and working memory, the right posterior Cg to visual-constructional abilities and the left Unc FA to Modified Trails Errors. After adding corresponding GM volumes, the left anterior Cg FA, the right anterior cingulate FA, the right posterior cingulate FA and the left uncinate FA remained significant predictors of the cognitive tasks. In the AD group, the left posterior Cg FA and right descending Cg FA were related to visual recall performance but did not remain significant predictors when GM volumes were added to the regression. These results suggest that reduced integrity of specific WM tracts contribute to cognitive deficits observed in bvFTD after accounting for GM atrophy. In AD, memory impairment was related to WM tract injury but this relationship was no longer observed when GM volumes were included. PMID- 22037959 TI - Updates in the management of the overactive bladder in patients with myelomeningocele. AB - Overactive bladder secondary to myelomeningocele provides a unique management problem to the health care provider. A randomized prospective trial has called into question the standard postnatal treatment closure of myelomeningocele, with antenatal closure acting as an acceptable alternative, although caution for maternal and fetal risks must be further delineated. While traditional techniques such as the Mitrofanoff procedure have become standard of care in allowing patient independence from care providers, modifications of the technique in addition to assimilation of minimally invasive approaches have further improved quality-of-life measurements for this patient population. Intravesical botulinum toxin injection therapy has provided acceptable outcomes, albeit transiently, in terms of improving bladder compliance and decreasing bladder pressures. Bladder neck revision, both endoscopically and surgically, have shown promise with minimal upper tract deterioration. Nerve rerouting for neurogenic bladder is a novel, albeit unproven, approach, its use remaining experimental at this point. Utilization of the multitude of emerging techniques will serve to optimize treatment in this otherwise complicated patient population, although consideration of the long-term consequence of each therapy has yet to be elucidated. PMID- 22037960 TI - Heme breakdown and ischemia/reperfusion injury in grafted liver during living donor liver transplantation. AB - Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can cause early graft injury. However, the detailed mechanism of I/R injury remains unknown. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme catabolism and results in the production of iron, carbon monoxide (CO), and biliverdin IXalpha. Furthermore, in animals, HO-1 has a protective effect against oxidative stress associated with I/R injury. However, in humans, the molecular mechanism and clinical significance of HO-1 remain unclear. We previously demonstrated that exhaled CO levels increase during LDLT, and postulated that this may indicate I/R injury. In this study, we elucidate the origin of increased exhaled CO levels and the role of HO-1 in I/R injury during LDLT. We studied 29 LDLT donors and recipients each. For investigation of HO-1 gene expression by polymerase chain reaction and HO-1 localization by immunohistological staining, liver biopsies from the grafted liver were conducted twice, once before and once after I/R. Exhaled CO levels and HO-1 gene expression levels significantly increased after I/R. In addition, HO-1 levels significantly increased after I/R in Kupffer cells. Furthermore, we found a significant positive correlation between exhaled CO levels and HO-1 gene expression levels. These results indicated that increased heme breakdown in the grafted liver is the source of increased exhaled CO levels. We also found a significant relationship between HO 1 gene expression levels and alanine aminotransferase (ALT) levels; i.e., the higher the HO-1 gene expression levels, the higher the ALT levels. These results suggest that HO-1-mediated heme breakdown is caused by I/R during LDLT, since it is associated with increased exhaled CO levels and liver damage. PMID- 22037961 TI - Dominant black-capped chickadees pay no maintenance energy costs for their wintering status and are not better at enduring cold than subordinate individuals. AB - Winter requires physiological adjustments in northern resident passerines. Cold acclimatization is generally associated with an increase in physiological maintenance costs, measured as basal metabolic rate (BMR), and cold endurance, reflected by summit metabolic rate (M(sum)). However, several northern species also form social groups in winter and a bird's hierarchical position may influence the size of its metabolically active organs as well as its BMR. Winter metabolic performance in these species may therefore reflect a complex set of adjustments to both seasonal climatic variations and social environment. We studied the effect of social status on parameters of cold acclimatization (body mass, size of fat reserves and pectoral muscles, BMR and M(sum)) in free-living black-capped chickadees (Poecile atricapillus). Birds that were structurally large and heavy for their body size, mostly dominant individuals, carried more fat reserves and had larger pectoral muscles. However, social status had little effect on metabolic performance in the cold. Indeed, M(sum) was independent of social rank while mass-corrected BMR was slightly lower in dominant individuals, likely due to a statistical dilution effect caused by large metabolically inactive fat reserves. BMR and M(sum), whether considered in terms of whole animal values, corrected for body mass or body size were nevertheless correlated, suggesting a functional link between these metabolic components. Our results therefore indicate that the energy cost of social dominance is not a generalized phenomenon in small wintering birds. PMID- 22037962 TI - Outcomes management: incorporating and sustaining processes critical to using outcome data to guide practice improvement. AB - An outcomes management system (OMS) greatly facilitates an organization or state achieving requirements regarding accountability and use of empirically based interventions. A case example of the authors' experience with a successful and enduring OMS is presented, followed by a review of the literature and a proposed model delineating the key components and benefits of an OMS. Building capacity to measure performance requires embedding utilization of youth-specific, clinically meaningful outcome data into the organization's processes and structures. An OMS measures outcomes associated with services, facilitates implementation of evidence-based practices, informs case decision making, enables better and more efficient clinical management, and provides aggregated information used to improve services. A case-specific supervisory model based on instantaneously available information, including progress to date, helps maximize consumer outcomes. Continuous quality improvement activities, which are databased and goal oriented, become a positive change management tool. This paper describes organizational processes that facilitate the development of a highly functional OMS. PMID- 22037963 TI - Neighborhood contexts and the mediating role of neighborhood social cohesion on health and psychological distress among Hispanic and non-Hispanic residents. AB - BACKGROUND: Neighborhood social cohesion (NSC) may contribute to understanding how neighborhood contexts influence the physical and mental health of residents. PURPOSE: We examined the relation of NSC to self-rated mental and physical health and evaluated the mediating role of NSC on relations between neighborhood socioeconomic status, ethnic composition, and health. METHODS: A sample of 3,098 Hispanic and non-Hispanic residents within 597 census tracts in metropolitan Phoenix, Arizona rated their health, psychological distress, and their perceptions of NSC. Census tract estimates provided neighborhood contextual measures. RESULTS: Neighborhood social cohesion was significantly related to better physical and mental health. Both individually rated NSC and neighborhood level NSC mediated relations between neighborhood contexts and health outcomes. Substantive findings were consistent across Hispanic and non-Hispanic residents. CONCLUSIONS: The findings have implications for improving ethnic and socioeconomic disparities in physical and mental health through attention to social cohesion among neighborhood residents. PMID- 22037964 TI - Adherence to risk factor management instructions after acute myocardial infarction: the role of emotional support and depressive symptoms. AB - BACKGROUND: Emotional support and depression may influence adherence to risk factor management instructions after acute myocardial infarction (AMI), but their role requires further investigation. PURPOSE: To examine the longitudinal association between perceived emotional support and risk factor management adherence and assess depressive symptoms as a moderator of this association. METHODS: Among 2,202 AMI patients, we assessed adherence to risk factor management instructions over the first recovery year. Modified Poisson mixed effects regression evaluated associations, with adjustment for demographic and clinical factors. RESULTS: Patients with low baseline support had greater risk of poor adherence over the first year than patients with high baseline support (relative risk [RR] = 1.20, 95% confidence interval [CI] = 1.02-1.43). In stratified analyses, low support remained a significant predictor of poor adherence for non-depressed (RR = 1.41, 95% CI = 1.23-1.61) but not depressed (RR = 1.01, 95% CI = 0.78-1.30) patients (p for interaction < 0.001). CONCLUSIONS: Low emotional support is associated with poor risk factor management adherence after AMI. This relationship is moderated by depression, with a significant relationship observed only among non-depressed patients. PMID- 22037965 TI - Cancer distress reduction with a couple-based skills training: a randomized controlled trial. AB - BACKGROUND: There are few interventions for couples facing cancer. PURPOSE: This study aims to investigate the utility of providing dyadic skills to these couples. METHODS: Woman recently diagnosed with breast or gynecological cancer and their partners were randomly assigned to either a couple-skills intervention (Side by Side) or to cancer education (Couples Control Program). Assessments with self-report and behavioral observation of both partners were conducted four times over 16 months. RESULTS: Multilevel analyses of data from 72 participating couples suggest that females receiving Side by Side showed larger reductions in fear of progression, and couples reported less avoidance in dealing with the cancer, more posttraumatic growth, and better relationship skills relative to the Couples Control Program. All differences favoring Side by Side disappeared by 16 months after the diagnosis. CONCLUSION: Short-term changes in functioning may be improved by enhancing couples' dyadic skills during acute medical treatment of the disease. PMID- 22037967 TI - Mercury emission and dispersion models from soils contaminated by cinnabar mining and metallurgy. AB - The laboratory flux measurement system (LFMS) and dispersion models were used to investigate the kinetics of mercury emission flux (MEF) from contaminated soils. Representative soil samples with respect to total Hg concentration (26-9770 MUg g(-1)) surrounding a decommissioned mercury-mining area (Las Cuevas Mine), and a former mercury smelter (Cerco Metalurgico de Almadenejos), in the Almaden mercury mining district (South Central Spain), were collected. Altogether, 14 samples were analyzed to determine the variation in mercury emission flux (MEF) versus distance from the sources, regulating two major environmental parameters comprising soil temperature and solar radiation. In addition, the fraction of the water-soluble mercury in these samples was determined in order to assess how MEF from soil is related to the mercury in the aqueous soil phase. Measured MEFs ranged from less than 140 to over 10,000 ng m(-2) h(-1), with the highest emissions from contaminated soils adjacent to point sources. A significant decrease of MEF was then observed with increasing distance from these sites. Strong positive effects of both temperature and solar radiation on MEF was observed. Moreover, MEF was found to occur more easily in soils with higher proportions of soluble mercury compared to soils where cinnabar prevails. Based on the calculated Hg emission rates and with the support of geographical information system (GIS) tools and ISC AERMOD software, dispersion models for atmospheric mercury were implemented. In this way, the gaseous mercury plume generated by the soil-originated emissions at different seasons was modeled. Modeling efforts revealed that much higher emissions and larger mercury plumes are generated in dry and warm periods (summer), while the plume is smaller and associated with lower concentrations of atmospheric mercury during colder periods with higher wind activity (fall). Based on the calculated emissions and the model implementation, yearly emissions from the "Cerco Metalurgico de Almadenejos" decommissioned metallurgical precinct were estimated at 16.4 kg Hg y(-1), with significant differences between seasons. PMID- 22037968 TI - [Prevalence of abnormal mucosal findings in patients in HNO practices]. AB - OBJECTIVE: To date, no secondary prevention program is in place for patients carrying an increased risk for developing head and neck cancer (HNSCC). In terms of successful, long-term curative therapy and increased quality of life, it would be useful to detect such diseases at an early stage. PATIENTS AND METHODS: A total of 370 patients with at least one risk factor such as "smoking", "alcohol", or "reflux disease" and without any symptoms were examined during a 1-year period using standard HNO methods (e. g. endoscopy) for suspicious alterations of the mucosa of the upper aerodigestive tract. RESULTS: In 13 (3.5%) of all 370 cases a biopsy was taken for further diagnosis. Squamous cell carcinoma was found in eight cases, while one further patient was suffering from non-Hodgkin lymphoma. CONCLUSIONS: It is simple and safe to examine patients at risk of developing HNSCC by standard HNO methods. The rate of detected carcinomas is much higher than in former investigations, likely because our survey focused only on patients with specific risk factors. PMID- 22037969 TI - [Falls and fall risk factors. Are they relevant in ENT outpatient medical care?]. AB - BACKGROUND AND OBJECTIVE: The risk of falling increases with age. The problem of falls in medical care constantly rises in priority due to demographic changes in Germany. Therefore, the risk of falling should be assessed in all patients. The present study was intended to evaluate the frequency of falls in daily ENT outpatient medical care and the importance of risk factors. PATIENTS/METHODS: A multicentre study was performed in six outpatient facilities based on a survey of falls and fall risk factors in patients living at home (n = 673) aged 60 years and older. RESULTS: Falls are a frequent problem in the elderly. A total of 23% had one and 13.7% more than one fall within the previous year. Of these, 15% suffered injury, while only 13% used some form of fall prevention. Joint pain and problems of the hip and lower extremities (42.6%), abnormal gait (41.3%), dizziness and balance disorders (38%) as well as impaired activities of daily living (35%) are the most common risk factors for falls and multiple falls in all age groups. Impaired hearing is a fall risk factor in elderly patients. CONCLUSIONS: Falls are a frequent problem in patients in ENT outpatient medical care. Fall prevention is advisable in the context of an interdisciplinary approach. PMID- 22037970 TI - Deletion of estrogen receptor beta accelerates early stage of bone healing in a mouse osteotomy model. AB - This study examined the role of estrogen receptor (ER) beta during mouse femoral fracture healing by employing ER knockout (KO) mice. The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification. INTRODUCTION: This study was conducted to examine the role of ER beta during fracture healing. METHODS: Female ERbeta knockout (KO) mice (18 weeks old) and age-matched female wild-type (WT) mice underwent open osteotomy on the right femur. They were sacrificed at 1, 2, 4 and 6 weeks post fracture. The sera and callus samples were subjected to the following analyses: micro-computed tomography (CT)-based angiography, micro-CT evaluation, histological examination, histomorphometry examination, real-time polymerase chain reaction (PCR) analysis, biochemical marker, and mechanical testing. RESULTS: Micro-CT-based angiography showed that the total vessel volume at the fracture site was larger in the KO group than the WT group at 1 and 2 weeks post fracture. Micro-CT analysis revealed that the callus volume was significantly higher in the KO group from week 2 to week 4 post-fracture when compared with the WT group consistent with the histological data. Analysis of biochemical markers indicated that circulating P1NP levels in the KO mice were significantly higher than in the WT mice from week 2 to week 4 and that temporal expression of circulating C-terminal telopeptide of type I collagen (CTX) levels was also higher in the KO mice than in the WT mice. These results were consistent with quantitative real-time PCR analysis. The ultimate load, stiffness, and energy to failure were significantly higher in the KO mice than in the WT mice at week 4. CONCLUSIONS: The fracture healing in KO mice was enhanced in the early stage of neovascularization and the middle stage of endochondral ossification, but not by the end of healing. Blockade of ERbeta can be considered as another therapeutic strategy for osteoporotic fracture and non-union fracture. PMID- 22037971 TI - The influence of participation in Better Bones and BalanceTM on skeletal health: evaluation of a community-based exercise program to reduce fall and fracture risk. AB - Older women participating in Better Bones and BalanceTM (BBB) had similar bone mass at the hip compared to a sample of low active/sedentary controls. However, both groups had higher than expected hip BMD, despite higher risk for osteoporosis among BBB participants. INTRODUCTION: BBB is a community-based fall and fracture risk reduction program shown to reduce bone loss at the hip in older women under controlled laboratory conditions. Whether bone benefits are derived from BBB as delivered in the community setting is unknown. The purpose of this study is to evaluate the relationship between community-based BBB participation and parameters of skeletal health in postmenopausal women. METHODS: Women were recruited from BBB classes (n=69) and compared to low active/sedentary controls (n=46); total sample aged 69 + 7.7 years. Bone mineral density (BMD) of the hip and spine was measured using DXA; hip bone structure [cross-sectional area, cross sectional moment of inertia] at the narrow neck and intertrochanter were derived using hip structural analysis software. Diet, physical activity, and health history were assessed by questionnaires. Group differences in bone outcomes were determined using ANCOVA controlling for age and body mass. RESULTS: While controls were heavier and exhibited greater total body BMD compared to BBB participants (p<0.05), there were no differences between groups in hip or spine BMD or bone structural outcomes (p>0.05) despite BBB participants reporting more frequent prior diagnoses of or risk factors for osteoporosis compared to controls. Both controls and BBB participants had higher than average T-scores at the hip (p<0.05) when compared to an age-matched cohort from NHANES. CONCLUSIONS: These data suggest that participation in BBB may not result in direct benefits to bone. However long-term participation may be associated with other positive outcomes. PMID- 22037972 TI - Quantitative ultrasound of the heel and fracture risk assessment: an updated meta analysis. AB - Meta-analysis of prospective studies shows that quantitative ultrasound of the heel using validated devices predicts risk of different types of fracture with similar performance across different devices and in elderly men and women. These predictions are independent of the risk estimates from hip DXA measures. INTRODUCTION: Clinical utilisation of heel quantitative ultrasound (QUS) depends on its power to predict clinical fractures. This is particularly important in settings that have no access to DXA-derived bone density measurements. We aimed to assess the predictive power of heel QUS for fractures using a meta-analysis approach. METHODS: We conducted an inverse variance random effects meta-analysis of prospective studies with heel QUS measures at baseline and fracture outcomes in their follow-up. Relative risks (RR) per standard deviation (SD) of different QUS parameters (broadband ultrasound attenuation [BUA], speed of sound [SOS], stiffness index [SI], and quantitative ultrasound index [QUI]) for various fracture outcomes (hip, vertebral, any clinical, any osteoporotic and major osteoporotic fractures) were reported based on study questions. RESULTS: Twenty one studies including 55,164 women and 13,742 men were included in the meta analysis with a total follow-up of 279,124 person-years. All four QUS parameters were associated with risk of different fracture. For instance, RR of hip fracture for 1 SD decrease of BUA was 1.69 (95% CI 1.43-2.00), SOS was 1.96 (95% CI 1.64 2.34), SI was 2.26 (95%CI 1.71-2.99) and QUI was 1.99 (95% CI 1.49-2.67). There was marked heterogeneity among studies on hip and any clinical fractures but no evidence of publication bias amongst them. Validated devices from different manufacturers predicted fracture risks with similar performance (meta-regression p values > 0.05 for difference of devices). QUS measures predicted fracture with a similar performance in men and women. Meta-analysis of studies with QUS measures adjusted for hip BMD showed a significant and independent association with fracture risk (RR/SD for BUA = 1.34 [95%CI 1.22-1.49]). CONCLUSIONS: This study confirms that heel QUS, using validated devices, predicts risk of different fracture outcomes in elderly men and women. Further research is needed for more widespread utilisation of the heel QUS in clinical settings across the world. PMID- 22037974 TI - Efficient and versatile synthesis of star polymers in water and their use as emulsifiers. AB - Core cross-linked star polymers of low polydispersity were efficiently prepared in high yield by RAFT-mediated emulsion and dispersion polymerizations in water at high solid content. These star polymers were demonstrated to be effective emulsifiers, and the emulsion was successfully used as template to fabricate polymer particles. PMID- 22037975 TI - Challenging the myth of urban regeneration: raising the profile of problem gambling with a media campaign. AB - This paper is an examination of discourses challenging the myth of 'gambling' as a form of urban regeneration in Great Britain. The focus is primarily on the Daily Mail, which has continually waged a successful media campaign to "Kill the Casino Bill" and constructed a powerful public condemnation of gambling as regenerative. From an analysis of 156 gambling articles from January 2004 to December 2010 common and recurring themes emerged to dismiss gambling as a form of regeneration. These were gambling as immoral, criminal and pathological. These helped shaped discourses around which the debate on gambling was framed and structured. PMID- 22037976 TI - Imageability estimates for 3,000 disyllabic words. AB - We provide imageability estimates for 3,000 disyllabic words (as supplementary materials that may be downloaded with the article from www.springerlink.com ). Imageability is a widely studied lexical variable believed to influence semantic and memory processes (see, e.g., Paivio, 1971). In addition, imageability influences basic word recognition processes (Plaut, McClelland, Seidenberg, & Patterson, 1996). In fact, neuroimaging studies have suggested that reading high- and low-imageable words elicits distinct neural activation patterns for the two types e.g., Bedny & Thompson-Schill (Brain and Language 98:127-139, 2006; Graves, Binder, Desai, Conant, & Seidenberg NeuroImage 53:638-646, 2010). Despite the usefulness of this variable, imageability estimates have not been available for large sets of words. Furthermore, recent megastudies of word processing e.g., Balota et al. (Behavior Research Methods 39:445-459, 2007) have expanded the number of words that interested researchers can select according to other lexical characteristics (e.g., average naming latencies, lexical decision times, etc.). However, the dearth of imageability estimates (as well as those of other lexical characteristics) limits the items that researchers can include in their experiments. Thus, these imageability estimates for disyllabic words expand the number of words available for investigations of word processing, which should be useful for researchers interested in the influences of imageability both as an input and as an outcome variable. PMID- 22037977 TI - Arduino: a low-cost multipurpose lab equipment. AB - Typical experiments in psychological and neurophysiological settings often require the accurate control of multiple input and output signals. These signals are often generated or recorded via computer software and/or external dedicated hardware. Dedicated hardware is usually very expensive and requires additional software to control its behavior. In the present article, I present some accuracy tests on a low-cost and open-source I/O board (Arduino family) that may be useful in many lab environments. One of the strengths of Arduinos is the possibility they afford to load the experimental script on the board's memory and let it run without interfacing with computers or external software, thus granting complete independence, portability, and accuracy. Furthermore, a large community has arisen around the Arduino idea and offers many hardware add-ons and hundreds of free scripts for different projects. Accuracy tests show that Arduino boards may be an inexpensive tool for many psychological and neurophysiological labs. PMID- 22037978 TI - The expression pattern of ADP-ribosyltransferase 3 in rat traumatic brain injury. AB - Mammalian ecto ADP-ribosyltransferases (ARTs) can regulate the biological functions of various types of cells by catalyzing the transfer of single ADP ribose moiety from NAD+ to a specific amino acid in a target protein. ART3 is a member of the known ART family which is involved in cell division, DNA-repair and the regulation of the inflammatory response. To elucidate the expression, cellular localization and possible functions of ART3 in central nervous system (CNS) lesion and repair, we performed an acute traumatic brain injury model in adult rats. Western blot analysis showed that the expression of ART3 in ipsilateral brain cortex increased, then reached a peak at day 3 after traumatic brain injury (TBI), and gradually declined during the following days. But in the contralateral brain cortex, no obvious alterations were observed. Immunohistochemistry revealed the highly significant accumulation of ART3 at the ipsilateral brain in comparison to contralateral cerebral cortex. Double immunofluorescence labeling suggested that ART3 was localized mainly in the plasmalemma of neurons, but not in astrocytes or microglias within 3 mm from the lesion site at day 3 post-injury. In addition, we detected the expression profiles of caspase-3 and growth associated protein 43 (GAP-43) whose changes were correlated with the expression profiles of ART3 in this TBI model. Besides, co-localization of ART3/active caspase-3 and ART3/GAP43 were detected in NeuN positive cells, respectively. Moreover, Pheochromocytoma (PC12) cells were treated with H2O2 to establish an apoptosis model. The results showed that the expression of ART3 was increased in the concentration and time dependence way. To further examine the involvement of ART3 in apoptosis of PC12, 3-Methoxybenzamide was used in flow cytometry analysis of apoptotic cells stained with Annexin V and PI. The experimental group in which 3-Methoxybenzamide used had a relative low level of apoptotic index compared with the untreated group. Together with previous reports, we hypothesize that ART3 may play important roles in CNS pathophysiology after TBI and further research is needed to have a good understanding of its function and mechanism. PMID- 22037979 TI - Intravenous tissue plasminogen activator treatment for ischemic stroke in dabigatran-treated patients. PMID- 22037980 TI - Chemokines as markers of local inflammation and angiogenesis in patients with chronic subdural hematoma: a prospective study. AB - OBJECTIVE: The goal of this study was to investigate the chemokines CCL2, CXCL8, CXCL9 and CXCL10 as markers of the inflammatory responses in chronic subdural hematoma (CSDH). METHODS: Samples of peripheral venous blood and CSDH fluid (obtained during surgery) in 76 adult patients were prospectively analyzed. Chemokine values were assessed by a Multiplex antibody bead kit. RESULTS: We found significantly higher levels of chemokines CCL2, CXCL8, CXCL9 and CXCL10 in hematoma fluid compared with serum. CONCLUSIONS: Chemokines are elevated in the hematoma cavity of patients with CSDH. It is likely that these signaling modulators play an important role in promoting local inflammation. Furthermore, biological activity of CCL2 and CXCL8 may promote neovascularization within the outer CSDH membrane, and a compensatory angiostatic activity of CXCL9 and CXCL10 may contribute to repairing this disorder. This phenomenon was restricted to the hematoma site, and the systemic chemokine levels might not reflect local immune responses. PMID- 22037981 TI - Pregnancy and childbirth after microsurgery for lumbar disc herniation. AB - BACKGROUND: The influence of previous lumbar discectomy on pregnancy and childbirth has not been extensively studied. This study reports the course of pregnancies after lumbar discectomy. METHOD: Twenty-six 31.5 +/- 3.6-year-old patients who had delivered 39 children were included. All patients underwent lumbar microsurgical discectomy prior to childbirth. Demographic and surgical data were collected from hospital records and patient questionnaires. The presence and course of low back pain (LBP) and radiculopathy signs were noted. FINDINGS: Mean latency between surgery and childbirth was 42.5 +/- 34.8 months. Delivery was at gestational week 36 to 42, and the average weight of the newborn was 3,390 +/- 0.490 g. Prevalence and new onset of symptoms during pregnancy was as follows: low back pain, 76% and 60%; leg pain 37% and 18%; motor deficits 13% and 6%; and sensory deficits 39% and 19%, respectively. No recurrent lumbar disc herniation was diagnosed within 6 months after pregnancy. Patients suffering from radicular pain during pregnancy were at risk of persistence of symptoms 6 months after delivery. Three patients had had surgery because of recurrent lumbar disc herniation during the follow-up of 7.73 +/- 2.66 years. CONCLUSIONS: The incidence of radicular pain during pregnancy after microsurgical discectomy for lumbar disc herniation was 18%. The incidence and prevalence of LBP are among the highest reported in the literature. The incidence of low back pain and radiculopathy signs does not change significantly with subsequent pregnancies. The operation rate for recurrent lumbar disc herniation or adjacent level disease after pregnancy seems not to be higher than the overall rate reported in the literature. PMID- 22037982 TI - Clinical relevance of blast-related traumatic brain injury. PMID- 22037983 TI - Fracture through the apex of a delta tibia (minor tibial duplication) following minor injury. AB - Delta tibia (also known as minor tibial duplication) is a rare variant of congenital anterolateral tibial bowing. It is not associated with neurofibromatosis or pseudarthrosis in which there are characteristic changes on the lateral radiograph. This deformity is not thought to be prone to fracture. We describe a child with this deformity, who during a 4-year period sustained two separate fractures following relatively minor trauma. In both circumstances, the injury healed well with no evidence of pseudarthrosis formation. PMID- 22037984 TI - Guidelines on the ethics of clinical research in anesthesia. PMID- 22037985 TI - Alternative site for median nerve blockade allowing early functional rehabilitation after hand surgery. AB - PURPOSE: In this report we describe an alternative approach to catheter placement for continuous selective median nerve blockade. It spared the finger movements and therefore allowed early postoperative rehabilitation in a patient who underwent surgical repair of the index finger flexor tendon. CLINICAL FEATURES: A patient with a complicated history of traumatic index finger flexor tendon rupture, surgical repair, failed rehabilitation due to poor postoperative pain control, adhesion formation, and subsequent rerupture due to tenolysis was admitted for reconstructive surgery. This time, a continuous regional block was used. Although the insertion of a catheter at the wrist level would have spared the anterior interosseous branch of the median nerve and preserved finger movements, a more distant site had to be chosen to avoid proximity to the surgical wound. Therefore, under combined ultrasonography and neurostimulation guidance, the catheter was inserted in the proximal one-third of the patient's forearm distal to the branching-off point of the anterior interosseous nerve. Continuous ropivacaine infusion was initiated and maintained until being stopped on the afternoon of the third postoperative day, providing good analgesia without interfering with postoperative physiotherapy, which was successfully completed during this hospitalization. CONCLUSION: Placement of a catheter for continuous median nerve blockade in the proximal one-third of the forearm for effective postoperative pain-free rehabilitation after hand surgery should be considered in cases in which the surgical incision extends toward the patient's wrist. The block site can be readily identified by a combined use of ultrasonography and neurostimulation guidance. PMID- 22037986 TI - Extubation of a difficult airway after thyroidectomy: use of a flexible bronchoscope via the LMA-ClassicTM. AB - PURPOSE: We report an extubation strategy for a patient scheduled for thyroidectomy who had several factors indicating that it would be a difficult extubation. CLINICAL FEATURES: A 75-yr-old man with thyroid cancer presented for total thyroidectomy. He had anatomical features predictive of a difficult upper airway. Therefore, his trachea was intubated while he was awake using a flexible bronchoscope. The tumour had invaded the trachea, necessitating total thyroidectomy, 3-cm tracheal resection, and primary tracheal anastomosis. The left recurrent laryngeal nerve (RLN) was inherently involved in the tumour and sacrificed. A "guardian suture" placed between the chin and the chest maintained the head and neck in flexion, thereby avoiding traction on the tracheal anastomosis. Immediate postoperative extubation was desirable, given the new tracheal anastomosis; however, complicating factors included left RLN paralysis, tracheal anastomosis, potential for tracheomalacia or supraglottic airway swelling, and the guardian suture preventing neck extension. In addition, there were anatomical features raising the suspicion of difficult reintubation should it be necessary. With the patient deeply anesthetized, the endotracheal tube was removed and replaced with the Laryngeal Mask Airway (LMA)-ClassicTM as a bridging device to facilitate bronchoscopic examination. It allowed us to visualize the tracheal repair, tracheal movement, vocal cord function, and supraglottic structures. The patient emerged from anesthesia and was extubated uneventfully. CONCLUSION: We describe a viable extubation strategy used in a patient after complex thyroid surgery involving tracheal resection. By using the LMA-ClassicTM as a bridging device and to facilitate bronchoscopic examination, we were able to address the above concerns and safely manage the extubation phase in this patient. PMID- 22037987 TI - Development of a pharmacist collaborative care program for pulmonary arterial hypertension. AB - Patients with Pulmonary Arterial Hypertension (PAH) require multidisciplinary care. Involving pharmacists in PAH multidisciplinary care teams may enhance patient education and improve medication use. We describe the implementation of a Pharmacist Collaborative Care Program (PCCP) in a PAH referral centre in Grenoble, France. Initiated in 2007, the PCCP program includes a pharmacist intervention whose goals are educational, psychosocial, and technical. During patient interviews, pharmacists make an 'educational diagnosis' and provide a patient-specific education session. Patient skills are evaluated at the end of the session. Pharmacists provide feedback to nurses and physicians through a standardized report form and discussion during medical rounds and PAH group meetings. Pharmacists re-evaluate patients' skills every 3-6 months during multidisciplinary clinical evaluations. The PCCP program for PAH is an established practice in Grenoble and may inform future patient education programs involving pharmacists in France, where legislation has recently been passed to standardize patient education. PMID- 22037988 TI - Pleomorphic basal cell carcinoma of the eyelid with true ductular differentiation. PMID- 22037989 TI - Writing out prescriptions: hyperrealism and the chemical regulation of mood. AB - Using contemporary literary sources, we explore the powerful ideological framework that normalises prescription dependency as part of everyday life, focusing upon the treatment of mood disorders. Through a literary critical methodology, we read novels by American hyperrealists such as Bret Easton Ellis, David Foster Wallace and Rick Moody as symptomatic of prescription culture. Though we argue that these writers brilliantly understand the dangers of mood medication, they do not escape its logic, rather, 'writing it out' as they write against it. Indeed, we propose that their novels bear ironic similarities to medical texts such as the British National Formulary, usually seen as a neutral handbook for physicians' guidance in prescribing. We explicate their method as that of deconstruction, which, in contrast to more obvious critiques of chemical treatment, such as therapy, neither analyses nor cures. Though this method underplays the possibility of pragmatic and political resistance exemplified by alternative formularies such as the long-established feminist health manual Our Bodies, Ourselves, we argue that its very ambiguity uniquely exposes the complex determinisms associated with prescribed medication. We thus propose the value of drawing on deconstructive literature to better understand 'health' interventions such as prescription drugs for the regulation of mood. PMID- 22037991 TI - Assessing habitat quality of farm-dwelling house sparrows in different agricultural landscapes. AB - Having historically been abundant throughout Europe, the house sparrow (Passer domesticus) has in recent decades suffered severe population declines in many urban and rural areas. The decline in rural environments is believed to be caused by agricultural intensification, which has resulted in landscape simplification. We used giving-up densities (GUDs) of house sparrows feeding in artificial food patches placed in farmlands of southern Sweden to determine habitat quality during the breeding season at two different spatial scales: the landscape and the patch scale. At the landscape scale, GUDs were lower on farms in homogeneous landscapes dominated by crop production compared to more heterogeneous landscapes with mixed farming or animal husbandry. At the patch level, feeding patches with a higher predation risk (caused by fitting a wall to the patch to obstruct vigilance) had higher GUDs. In addition, GUDs were positively related to population size, which strongly implies that GUDs reflect habitat quality. However, the increase followed different patterns in homogeneous and heterogeneous landscapes, indicating differing population limiting mechanisms in these two environments. We found no effect of the interaction between patch type and landscape type, suggesting that predation risk was similar in both landscape types. Thus, our study suggests that simplified landscapes constitute a poorer feeding environment for house sparrows during breeding, that the population regulating mechanisms in the landscapes differ, but that predation risk is the same across the landscape types. PMID- 22037992 TI - Irreversibility of a bad start: early exposure to osmotic stress limits growth and adaptive developmental plasticity. AB - Harsh environments experienced early in development have immediate effects and potentially long-lasting consequences throughout ontogeny. We examined how salinity fluctuations affected survival, growth and development of Fejervarya limnocharis tadpoles. Specifically, we tested whether initial salinity effects on growth and rates of development were reversible and whether they affected the tadpoles' ability to adaptively accelerate development in response to deteriorating conditions later in development. Tadpoles were initially assigned to either low or high salinity, and then some were switched between salinity levels upon reaching either Gosner stage 30 (early switch) or 38 (late switch). All tadpoles initially experiencing low salinity survived whereas those initially experiencing high salinity had poor survival, even if switched to low salinity. Growth and developmental rates of tadpoles initially assigned to high salinity did not increase after osmotic stress release. Initial low salinity conditions allowed tadpoles to attain a fast pace of development even if exposed to high salinity afterwards. Tadpoles experiencing high salinity only late in development metamorphosed faster and at a smaller size, indicating an adaptive acceleration of development to avoid osmotic stress. Nonetheless, early exposure to high salinity precluded adaptive acceleration of development, always causing delayed metamorphosis relative to those in initially low salinity. Our results thus show that stressful environments experienced early in development can critically impact life history traits, having long-lasting or irreversible effects, and restricting their ability to produce adaptive plastic responses. PMID- 22037993 TI - A meta-analysis of plant physiological and growth responses to temperature and elevated CO(2). AB - Atmospheric carbon dioxide (CO(2)) and global mean temperature are expected to be significantly higher by the end of the 21st century. Elevated CO(2) (eCO(2)) and higher temperature each affect plant physiology and growth, but their interactive effects have not been reviewed statistically with respect to higher chronic mean temperatures and abrupt heat stress. In this meta-analysis, we examined the effect of CO(2) on the physiology and growth of plants subjected to different temperature treatments. The CO(2) treatments were categorized into ambient (<400 ppm) or elevated (>560 ppm) levels, while temperature treatments were categorized into ambient temperature (AT), elevated temperature (ET; AT + 1.4-6 degrees C), or heat stress (HS; AT + >8 degrees C). Plant species were grouped according to photosynthetic pathways (C(3), C(4)), functional types (legumes, non-legumes), growth forms (herbaceous, woody), and economic purposes (crop, non-crop). eCO(2) enhanced net photosynthesis at AT, ET, and HS in C(3) species (especially at the HS level), but in C(4) species, it had no effect at AT, a positive effect at ET, and a negative effect at HS. The positive effect of eCO(2) on net photosynthesis was greater for legumes than for non-legumes at HS, for non-crops than crops at ET, and for woody than herbaceous species at ET and HS. Total (W (T)) and above- (W (AG)) and below-ground (W (BG)) biomass were increased by eCO(2) for most species groups at all temperatures, except for C(4) species and W (BG) of legumes at HS. Hence, eCO(2) * heat effects on growth were often not explained by effects on net photosynthesis. Overall, the results show that eCO(2) effects on plant physiology and growth vary under different temperature regimes, among functional groups and photosynthetic pathways, and among response variables. These findings have important implications for biomass accumulation and ecosystem functioning in the future when the CO(2) level is higher and climate extremes, such as heat waves, become more frequent. PMID- 22037994 TI - CT of the adrenal gland: the many faces of adrenal hemorrhage. AB - Adrenal hemorrhage is rarely suspected clinically, exhibits no specific clinical symptoms or laboratory findings, and yet is immediately life-threatening when bilateral. Recognition of adrenal hematomas is complicated by the variable appearance of these lesions. We survey the ways in which adrenal hematomas can appear on CT and provide strategies for differentiating hematomas from other adrenal pathologies. PMID- 22037995 TI - Development of an ICT-based ratiometric fluorescent hypochlorite probe suitable for living cell imaging. AB - We have judiciously constructed a novel ICT-based ratiometric OCl(-) probe capable of ratiometric imaging in the live cells based on the new OCl(-)-promoted de-diaminomaleonitrile reaction. PMID- 22037996 TI - Explaining the motherhood wage penalty during the early occupational career. AB - Prior research shows that mothers earn lower hourly wages than women without children, and that this maternal wage penalty cannot be fully explained by differences between mothers and other women in work experience and job characteristics. This research examines whether the residual motherhood wage penalty results from differences between mothers and other women in the accumulation of work interruptions and breaks in schooling. Using longitudinal data for 486 women followed from ages 19 to 31 in the Minnesota Youth Development Study, we find that accumulated months not in the labor force and not enrolled in school explain the residual pay gap between mothers and other women. PMID- 22037997 TI - Treatment of ocular myasthenia gravis. AB - OPINION STATEMENT: Myasthenia gravis (MG) is an autoimmune disorder that is characterized by variable weakness and fatigability. Often, MG presents with only ocular symptoms such as ptosis and diplopia. Treatment of ocular MG is aimed at relieving the symptoms of ptosis and diplopia, as well as preventing the development of generalized MG symptoms. Immune suppression with steroids is often the main therapy. Steroid doses must be increased slowly because of a risk of precipitating myasthenic crisis. After achieving the highest target dose, steroids are then slowly tapered down to the lowest effective dose. Often, acetylcholinesterase inhibitors such as pyridostigmine and neostigmine are also employed to help control symptoms. When steroids are contraindicated, acetylcholinesterase inhibitors can be tried as the primary therapy. Steroid sparing agents such as azathioprine and mycophenolate may also have a role in treating ocular MG. Other treatments for MG include plasmapheresis, intravenous immunoglobulin, and other immunosuppressive agents, but these are rarely required for ocular MG. Patients should also be evaluated for thymoma. Thymoma should be resected surgically. Ocular MG without thymoma is not usually treated with thymectomy. Topical agents may be useful as additional therapy for mild or moderate ptosis. Nonpharmacologic treatments include occlusive devices, prisms, eyelid supports, contact lenses, and (in long-standing, stable cases) strabismus surgery or eyelid elevation surgery. PMID- 22037998 TI - Treatment of vision loss in giant cell arteritis. AB - OPINION STATEMENT: If giant cell arteritis is suspected as a cause of visual loss, emergent management is necessary. Clinical suspicion should prompt the practitioner to obtain laboratory studies and initiate treatment prior to establishing the diagnosis. The evaluation includes immediate erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complete blood count (CBC). Treatment begins with high-dose intravenous corticosteroids. We recommend intravenous methylprednisolone (250 mg every 6 h) for 3 to 5 days. During that time, a temporal artery biopsy should be performed for pathologic diagnosis. We also begin daily adjunctive aspirin orally. After the initial bolus of intravenous corticosteroids, therapy transitions to oral prednisone administered at 1 mg/kg per day until the activity of the disease process attenuates, as demonstrated by improvement in systemic symptoms and normalization of both ESR and CRP. This change usually occurs in the first 3 to 4 weeks. The patient should be followed closely, with therapy tapered as guided by systemic symptoms, ESR, and CRP. To maximize the use of remaining vision, appropriate patients should be referred to specialists for help with low-vision therapies, assistive devices, and precautions to protect the better-seeing eye. PMID- 22037999 TI - Darwin and his pigeons. The analogy between artificial and natural selection revisited. AB - The analogy between artificial selection of domestic varieties and natural selection in nature was a vital element of Darwin's argument in his Origin of Species. Ever since, the image of breeders creating new varieties by artificial selection has served as a convincing illustration of how the theory works. In this paper I argue that we need to reconsider our understanding of Darwin's analogy. Contrary to what is often assumed, nineteenth-century animal breeding practices constituted a highly controversial field that was fraught with difficulties. It was only with considerable effort that Darwin forged his analogy, and he only succeeded by downplaying the importance of two other breeding techniques - crossing of varieties and inbreeding - that many breeders deemed essential to obtain new varieties. Part of the explanation for Darwin's gloss on breeding practices, I shall argue, was that the methods of his main informants, the breeders of fancy pigeons, were not representative of what went on in the breeding world at large. Darwin seems to have been eager to take the pigeon fanciers at their word, however, as it was only their methods that provided him with the perfect analogy with natural selection. Thus while his studies of domestic varieties were important for the development of the concept of natural selection, the reverse was also true: Darwin's comprehension of breeding practices was moulded by his understanding of the working of natural selection in nature. Historical studies of domestic breeding practices in the eighteenth and nineteenth century confirm that, besides selection, the techniques of inbreeding and crossing were much more important than Darwin's interpretation allowed for. And they still are today. This calls for a reconsideration of the pedagogic use of Darwin's analogy too. PMID- 22038000 TI - Classification of breast lesions based on a dual S-shaped logistic model in dynamic contrast enhanced magnetic resonance imaging. AB - This study proposes a novel dual S-shaped logistic model for automatically quantifying the characteristic kinetic curves of breast lesions and for distinguishing malignant from benign breast tumors on dynamic contrast enhanced (DCE) magnetic resonance (MR) images. D(alpha,beta) is the diagnostic parameter derived from the logistic model. Significant differences were found in D(alpha,beta) between the malignant benign groups. Fisher's Linear Discriminant analysis correctly classified more than 90% of the benign and malignant kinetic breast data using the derived diagnostic parameter (D(alpha,beta)). Receiver operating characteristic curve analysis of the derived diagnostic parameter (D(alpha,beta)) indicated high sensitivity and specificity to differentiate malignancy from benignancy. The dual S-shaped logistic model was effectively used to fit the kinetic curves of breast lesions in DCE-MR. Separation between benign and malignant breast lesions was achieved with sufficient accuracy by using the derived diagnostic parameter D(alpha,beta) as the lesion's feature. The proposed method therefore has the potential for computer-aided diagnosis in breast tumors. PMID- 22038001 TI - Dynamic expression of the LAP family of genes during early development of Xenopus tropicalis. AB - The leucine-rich repeats and PDZ (LAP) family of genes are crucial for the maintenance of cell polarity as well as for epithelial homeostasis and tumor suppression in both vertebrates and invertebrates. Four members of this gene family are known: densin, erbin, scribble and lano. Here, we identified the four members of the LAP gene family in Xenopus tropicalis and studied their expression patterns during embryonic development. The Xenopus LAP proteins show a conserved domain structure that is similar to their homologs in other vertebrates. In Xenopus embryos, these genes were detected in animal cap cells at the early gastrula stage. At later stages of development, they were widely expressed in epithelial tissues that are highly polar in nature, including the neural epithelia, optic and otic vesicles, and in the pronephros. These data suggest that the roles of the Xenopus LAP genes in the control of cell polarity and morphogenesis are conserved during early development. Erbin and lano show similar expression patterns in the developing head, suggesting potential functional interactions between the two molecules in vivo. PMID- 22038002 TI - Effects of fasting and refeeding on expression of MAFbx and MuRF1 in chick skeletal muscle. AB - The present study investigated the effects of fasting and refeeding on the expression of proteasome-related genes and their downstream targets in the skeletal muscles of chicks. Seven-day-old chicks were fasted for 24 or 48 h and then refed for 4 h. The expression levels of MAFbx and MuRF1, which function as E3 ligases in the ubiquitin-proteasome system, were investigated at the mRNA and protein levels. MAFbx and MuRF1 expression were increased by fasting and these increases were downregulated by refeeding. The expression of the target proteins of these E3 ligases, MyoD and M-CK, was also analyzed. The levels of these proteins were downregulated by fasting, and these decreases were rescued by refeeding. The results of this study indicate that fasting stimulates MAFbx and MuRF1 expression in chicks, possibly leading to increased degradation of their corresponding target proteins. PMID- 22038003 TI - Inhibition of adipogenic differentiation by myostatin is alleviated by arginine supplementation in porcine-muscle-derived mesenchymal stem cells. AB - Porcine mesenchymal stem cells in postnatal muscle have been demonstrated to differentiate into adipocytes. This increases adipocyte number and lipid accumulation, and is thought to be the origin of intramuscular fat. In this study, the effects of myostatin and arginine on adipogenic differentiation in mesenchymal stem cells derived from porcine muscle (pMDSCs) were investigated in vitro. Intracellular triglyceride levels were reduced by exogenous myostatin and increased by arginine supplementation or myostatin antibody (P<0.01). The inhibition of lipid accumulation by myostatin in pMDSCs was alleviated by arginine supplementation (P<0.01). Expression patterns of adipogenic transcription factors showed that exogenous myostatin suppressed PPARgamma2 and aP2 expression (P<0.01), while supplemental arginine or myostatin antibody promoted ADD1 expression (P<0.01). Furthermore, compared with the addition of either myostatin protein or antibody alone, ADD1 and PPARdelta expression were promoted by the combination of arginine and myostatin (P<0.01), and arginine combined with myostatin antibody promoted the expression of ADD1, PPARdelta, C/EBPalpha, PPARgamma2 and LPL in pMDSCs (P<0.05). These results suggest that myostatin inhibits adipogenesis in pMDSCs, and that this can be alleviated by arginine supplementation, at least in part, through promoting ADD1 and PPARdelta expression. PMID- 22038004 TI - Mitogenomic analysis of the genus Panthera. AB - The complete sequences of the mitochondrial DNA genomes of Panthera tigris, Panthera pardus, and Panthera uncia were determined using the polymerase chain reaction method. The lengths of the complete mitochondrial DNA sequences of the three species were 16990, 16964, and 16773 bp, respectively. Each of the three mitochondrial DNA genomes included 13 protein-coding genes, 22 tRNA, two rRNA, one O(L)R, and one control region. The structures of the genomes were highly similar to those of Felis catus, Acinonyx jubatus, and Neofelis nebulosa. The phylogenies of the genus Panthera were inferred from two combined mitochondrial sequence data sets and the complete mitochondrial genome sequences, by MP (maximum parsimony), ML (maximum likelihood), and Bayesian analysis. The results showed that Panthera was composed of Panthera leo, P. uncia, P. pardus, Panthera onca, P. tigris, and N. nebulosa, which was included as the most basal member. The phylogeny within Panthera genus was N. nebulosa (P. tigris (P. onca (P. pardus, (P. leo, P. uncia)))). The divergence times for Panthera genus were estimated based on the ML branch lengths and four well-established calibration points. The results showed that at about 11.3 MYA, the Panthera genus separated from other felid species and then evolved into the several species of the genus. In detail, N. nebulosa was estimated to be founded about 8.66 MYA, P. tigris about 6.55 MYA, P. uncia about 4.63 MYA, and P. pardus about 4.35 MYA. All these estimated times were older than those estimated from the fossil records. The divergence event, evolutionary process, speciation, and distribution pattern of P. uncia, a species endemic to the central Asia with core habitats on the Qinghai Tibetan Plateau and surrounding highlands, mostly correlated with the geological tectonic events and intensive climate shifts that happened at 8, 3.6, 2.5, and 1.7 MYA on the plateau during the late Cenozoic period. PMID- 22038005 TI - Characteristics of the phytoplankton community and bioaccumulation of heavy metals during algal blooms in Xiangjiang River (Hunan, China). AB - The frequency of algal blooms has increased in the mid and downstream reaches of the Xiangjiang River (Hunan, China), one of the most heavily polluted rivers in China. We identified the bloom-forming species in a bloom that occurred mid-late September 2010. In addition, we determined the extent of metal bioaccumulation in the algae and measured the toxicity of the algae using a mouse bioassay. Water samples were collected at upstream (Yongzhou), midstream (Hengyang), and downstream (Zhuzhou, Xiangtan, and Changsha) sites. The dominant species was Aulacoseira granulata, formerly known as Melosira granulata. The heaviest bloom occurred at Xiangtan and Changsha, where the number of A. granulata peaked at 1.3*10(5) filaments L(-1) and chlorophyll a at 0.04 mg L(-1). Concentrations of Al, Fe, and Mn were 4.4*10(3), 768.4, and 138.7 mg kg(-1) dry weight in the phytoplankton. The bioaccumulation factor was 4.0*10(5), 7.7*10(5), and 3.2*10(3), respectively. The heavy metal Pb had the greatest tendency to bioaccumulate among the highly toxic heavy metals, with a concentration of 19.2 mg kg(-1) dry weight and bioaccumulation factor of 9.6*10(3). The mouse bioassay suggested the bloom was toxic. The LD(50) was 384 mg kg(-1) and all surviving mice lost weight during the first 72 h after exposure. Our results demonstrate that blooms of A. granulata in rivers contaminated with heavy metals pose a threat to freshwater ecosystems and human health. Thus, measures should be taken to control eutrophication and heavy metal pollution in such rivers. PMID- 22038006 TI - Evaluation of upper limb muscle fatigue based on surface electromyography. AB - Fatigue is believed to be a major contributory factor to occupational injuries in machine operators. The development of accurate and usable techniques to measure operator fatigue is therefore important. In this study, we used a novel method based on surface electromyography (sEMG) of the biceps brachii and the Borg scale to evaluate local muscle fatigue in the upper limb after isometric muscle action. Thirteen young males performed isometric actions with the upper limb at different force levels. sEMG activities of the biceps brachii were recorded during the actions. Borg scales were used to evaluate the subjective sensation of local fatigue of the biceps brachii after the actions. sEMG activities were analyzed using the one-third band octave method, and an equation to determine the degree of fatigue was derived based on the relationship between the variable and the Borg scale. The results showed that the relationship could be expressed by a conic curve, and could be used to evaluate muscle fatigue during machine operation. PMID- 22038007 TI - High-performance single-chip exon capture allows accurate whole exome sequencing using the Illumina Genome Analyzer. AB - Here we present an adaptation of NimbleGen 2.1M-probe array sequence capture for whole exome sequencing using the Illumina Genome Analyzer (GA) platform. The protocol involves two-stage library construction. The specificity of exome enrichment was approximately 80% with 95.6% even coverage of the 34 Mb target region at an average sequencing depth of 33-fold. Comparison of our results with whole genome shot-gun resequencing results showed that the exome SNP calls gave only 0.97% false positive and 6.27% false negative variants. Our protocol is also well suited for use with whole genome amplified DNA. The results presented here indicate that there is a promising future for large-scale population genomics and medical studies using a whole exome sequencing approach. PMID- 22038008 TI - Accurate assessment of antibiotic susceptibility and screening resistant strains of a bacterial population by linear gradient plate. AB - The dynamics of a bacterial population exposed to the minimum inhibitory concentration (MIC) of an antibiotic is an important issue in pharmacological research. Therefore, a novel antibiotic susceptibility test is urgently needed that can both precisely determine the MIC and accurately select antibiotic resistant strains from clinical bacterial populations. For this purpose, we developed a method based on Fick's laws of diffusion using agar plates containing a linear gradient of antibiotic. The gradient plate contained two layers. The bottom layer consisted of 15 mL agar containing the appropriate concentration of enrofloxacin and allowed to harden in the form of a wedge with the plate slanted such that the entire bottom was just covered. The upper layer consisted of 15 mL plain nutrient agar added with the plate held in the horizontal position. After allowing vertical diffusion of the drug from the bottom agar layer for 12 h, the enrofloxacin concentration was diluted in proportion to the ratio of the agar layer thicknesses. The uniform linear concentration gradient was verified by measuring the enrofloxacin concentration on the agar surface. When heavy bacterial suspensions were spread on the agar surface and incubated for more than 12 h, only resistant cells were able to form colonies beyond the boundary of confluent growth of susceptible cells. In this way, the true MIC of enrofloxacin was determined. The MICs obtained using this linear gradient plate were consistent with those obtained using conventional antibiotic susceptibility tests. Discrete colonies were then spread onto a gradient plate with higher antibiotic concentrations; the boundary line increased significantly, and gene mutations conferring resistance were identified. This new method enables the rapid identification of resistant strains in the bacterial population. Use of the linear gradient plate can easily identify the precise MIC and reveal the dynamic differentiation of bacteria near the MIC. This method allows the study of genetic and physiological characteristics of individual strains, and may be useful for early warning of antibiotic resistance that may occur after use of certain antimicrobial agents, and guide clinical treatment. PMID- 22038009 TI - Meditation promotes insightful problem-solving by keeping people in a mindful and alert conscious state. AB - Although previous studies have shown that sleep can inspire insight, it is still unclear whether meditation can promote insight. Meditation differs from other types of passive rest such as relaxation and sleep because it requires full consciousness and mindfulness of targets such as one's breathing. Forty-eight university students without meditation experience were recruited to learn a simple meditation technique. They were given a list of 10 insight problems to solve (the pre-test session). In this study, we focused on the unsolved problems and examined if they could be successfully solved after a 20 min rest interval with or without meditation. Results showed that relative to the control group that listened to Chinese or English words and made a language judgment, the groups who learned meditation successfully solved significantly more failed problems from the pre-test session, providing direct evidence for the role of meditation in promoting insight. Further analysis showed that maintaining a mindful and alert state during meditation (raising a hand to report every 10 deep breaths compared to every 100 deep breaths) resulted in more insight regarding the failed items from the pre-test session. This implies that it was watchfulness in meditation, rather than relaxation, that actually contributed to insight. Consistently, in the meditation session or control task, the percentage of alpha waves-a brain index of mental relaxation-was negatively correlated with insight. These results suggest a meditation-based insight-promoting mechanism different from that involved in passive rest such as relaxation and sleep. PMID- 22038010 TI - Nasopharyngeal carcinoma: advances in genomics and molecular genetics. PMID- 22038011 TI - Inflammation, lipid metabolism dysfunction, and hypertension: active research fields in atherosclerosis-related cardiovascular disease in China. PMID- 22038013 TI - Multi-focal EBV-mucocutaneous ulcer heralding late-onset T-cell immunodeficiency in a woman with lupus erythematosus. PMID- 22038014 TI - Motor disability in the setting of oral anticoagulant therapy. PMID- 22038015 TI - Discrepancy in EBV-DNA load between peripheral blood and cerebrospinal fluid in a patient with isolated CNS post-transplant lymphoproliferative disorder. AB - Post-transplant lymphoproliferative disorder (PTLD) is a fatal complication of allogeneic hematopoietic stem cell transplantation (HSCT) that is caused by reactivation of Epstein-Barr virus (EBV). A successful approach, monitoring EBV DNA load in peripheral blood (PB) accompanied by preemptive rituximab therapy, has recently been reported. Here, we describe a 29-year-old woman who developed isolated central nervous system (CNS) PTLD. She received HSCT against acute myelogenous leukemia from a related human leukocyte antigen-haploidentical donor, following a conditioning regimen that included antithymocyte globulin. Tacrolimus and methylprednisolone were given as prophylaxis for graft-versus-host disease. On day +172, the patient's consciousness deteriorated. Magnetic resonance imaging showed six ring-enhanced lesions in the cerebral hemispheres. These tumors were diagnosed, via a craniotomy and tumorectomy, as PTLD. EBV-DNA load was elevated in the cerebrospinal fluid (CSF) but not detected in PB. She was treated with whole-brain irradiation and rituximab, and achieved partial remission of the tumors. This case serves as a reminder that vigilance is required regarding the development of isolated CNS PTLD; it is worth examining EBV-DNA replication in CSF for diagnosis even when the EBV-DNA load is negative in PB. PMID- 22038016 TI - MK886 inhibits the proliferation of HL-60 leukemia cells by suppressing the expression of mPGES-1 and reducing prostaglandin E2 synthesis. AB - Microsomal prostaglandin E synthase-1 (mPGES-1), an inducible enzyme that specifically catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), has been reported to be over-expressed in a variety of solid tumor cells and tissues, but not in normal tissues. Its association with leukemia, however, has not been fully investigated. Our study revealed, for the first time, that mPGES-1 is over-expressed in human acute myeloid leukemia HL-60 cells. Cytotoxicity assays and flow cytometry showed that MK886, an inhibitor of mPGES 1, inhibits proliferation of HL-60 cells and induces apoptosis in a dose- and time-dependent manner, which may result from down-regulation of mPGES-1 expression and PGE2 synthesis. Evaluation of mediators of apoptotic signaling revealed up-regulation of BAX expression and caspase-3 activity, as well as significant decreases in Bcl2 and P-Akt. We conclude that MK886 reduces the viability of leukemia HL-60 cells by reducing mPGES-1 expression and PGE2 synthesis in a dose-dependent manner, which strongly suggests that mPGES-1 inhibitors should be considered as promising candidates for leukemia treatment. PMID- 22038017 TI - Interlaboratory evaluation of trace element determination in workplace air filter samples by inductively coupled plasma mass spectrometry. AB - Inductively coupled plasma mass spectrometry (ICP-MS) is becoming more widely used for trace elemental analysis in the occupational hygiene field, and consequently new ICP-MS international standard procedures have been promulgated by ASTM International and ISO. However, there is a dearth of interlaboratory performance data for this analytical methodology. In an effort to fill this data void, an interlaboratory evaluation of ICP-MS for determining trace elements in workplace air samples was conducted, towards fulfillment of method validation requirements for international voluntary consensus standard test methods. The study was performed in accordance with applicable statistical procedures for investigating interlaboratory precision. The evaluation was carried out using certified 37-mm diameter mixed-cellulose ester (MCE) filters that were fortified with 21 elements of concern in occupational hygiene. Elements were spiked at levels ranging from 0.025 to 10 MUg filter(-1), with three different filter loadings denoted "Low", "Medium" and "High". Participating laboratories were recruited from a pool of over fifty invitees; ultimately twenty laboratories from Europe, North America and Asia submitted results. Triplicates of each certified filter with elemental contents at three different levels, plus media blanks spiked with reagent, were conveyed to each volunteer laboratory. Each participant was also provided a copy of the test method which each participant was asked to follow; spiking levels were unknown to the participants. The laboratories were requested to prepare the filters by one of three sample preparation procedures, i.e., hotplate digestion, microwave digestion or hot block extraction, which were described in the test method. Participants were then asked to analyze aliquots of the prepared samples by ICP-MS, and to report their data in units of MUg filter( 1). Most interlaboratory precision estimates were acceptable for medium- and high level spikes (RSD <25%), but generally yielded greater uncertainties than were anticipated at the outset of the study. PMID- 22038018 TI - Cyclooxygenase-dependent signaling is causally linked to non-melanoma skin carcinogenesis: pharmacological, genetic, and clinical evidence. AB - Cyclooxygenase (COX)-derived prostaglandins (PGs) exhibit manifold functions in acute and chronic skin inflammation induced by a number of physical (ultraviolet (UV) light, wounding) and chemical (12-O-tetradecanoylphorbol 13-acetate (TPA), arachidonic acid) noxious stimuli. Depending on the challenge and the context, constitutively expressed COX-1 or the transiently induced COX-2 isoform are of relevance. Moreover, squamous cell carcinoma (SCC) of skin is a prominent example of epithelial neoplasia that consistently overexpresses COX-2 in the parenchyme and the mesenchyme of premalignant and malignant lesions, while COX-1 expression remains unaltered. Pharmacological, clinical, and experimental animal studies as well as a few epidemiological studies document the importance of PG signaling in non-melanoma skin cancer including SCC and basal cell carcinoma (BCC) in humans and mice. Increased levels of PGE(2) and PGF(2alpha) in premalignant and/or malignant epithelial skin cancers are due to the constitutive upregulation of enzymes involved in PG biosynthesis, such as COX-2, and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase (15-PGDH), which is involved in the inactivation of PG, thus counteracting the activities of COX. Most remarkably, genetic studies show that mice which are deficient in COX-2 or COX-1 are protected from the development of SCC when applying the multi-stage chemical carcinogenesis protocol. Conversely, the forced overexpression of COX-2 in the proliferative basal compartment of the stratified skin epidermis results in spontaneous hyperplasia and dysplasia in transgenic mice and furthermore a sensitization for cancer development by conferring an auto-promoted skin phenotype. In multi-stage carcinogenesis, it also becomes clear that aberrant COX 2 overexpression and activity are causally involved in tumor promotion and tumor progression rather than initiation. In contrast, using as inducer of carcinogenesis the complete carcinogen UV B light, depletion of COX-2 but not of COX-1 makes mouse skin resistant for SCC, indicating that here, only COX-2 is essential. Depending on the type of challenge, COX-2-dependent signaling contributes to the pre-invasive growth of the skin epidermis by a delayed onset of terminal differentiation, or stimulation of hyperproliferation and survival. With respect to BCC, the genetic ablation of COX-2 but also of COX-1 leads to a strongly reduced tumor burden in the skin of Patched (Ptch)1(+/-) mice, which due to the deletion of a Ptch1 allele, spontaneously develop BCC resembling human familial basal cell nevus syndrome and sporadic BCC. Nonsteroidal anti inflammatory drugs and the COX-2-selective inhibitors (COXibs) exhibit impressive efficacy inhibiting tumor burden in various mouse models of SCC and BCC. Most importantly, in humans the interruption of COX-2 signaling is an effective strategy to treat and chemo-prevent non-melanoma skin cancer in individuals who are at high risk for the disease. However, any potential beneficial effect of this medicine has to be balanced against the adverse effects that are known to be associated with these drugs in a subset of patients. PMID- 22038020 TI - The inhibitory effect and the molecular mechanism of glabridin on RANKL-induced osteoclastogenesis in RAW264.7 cells. AB - Osteoblastic bone formation and osteoclastic bone resorption are in balance to maintain a constant, homeostatically controlled amount of bone. Excessive bone resorption by osteoclasts is involved in the pathogenesis of bone-related disorders. In the present study, we evaluated the inhibitory effects of glabridin, a flavonoid purified from licorice root, on the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation and its molecular mechanisms in murine osteoclast progenitor RAW264.7 cells. Glabridin significantly inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity, the formation of multinucleated osteoclasts and resorption-pit formation. In mechanistic studies of the anti-osteoclastogenic potential of glabridin, we found that glabridin inhibited RANKL-induced expression of c-Fos and subsequent expression of NFATc1, which is a master regulator of osteoclastogenesis. Interestingly, glabridin inhibited the RANKL-induced expression of signaling molecules (TRAF6, GAB2, ERK2, JNK1 and MKK7) and osteoclast survival-related signaling pathways such as c-Src, PI3K and Akt2. Glabridin also inhibited the bone resorptive activity of mature osteoclasts by inhibiting osteoclast-associated genes (cathepsin K, MMP-9, CAII, TCIRG1, OSTM1 and CLCN7). Taken together, our data suggest that glabridin holds great promise for use in preventing osteoclastogenesis by inhibiting RANKL-induced activation of signaling molecules and subsequent transcription factors in osteoclast precursors and these findings may be useful for evaluating treatment options in bone-destructive diseases. PMID- 22038019 TI - Cannabinoids, endocannabinoids, and cancer. AB - The endocannabinoid system consists of an array of endogenously produced bioactive lipids that activate cannabinoid receptors. Although the primary focus of endocannabinoid biology has been on neurological and psychiatric effects, recent work has revealed several important interactions between the endocannabinoid system and cancer. Several different types of cancer have abnormal regulation of the endocannabinoid system that contributes to cancer progression and correlates to clinical outcomes. Modulation of the endocannabinoid system by pharmacological agents in various cancer types reveals that it can mediate antiproliferative and apoptotic effects by both cannabinoid receptor-dependent and -independent pathways. Selective agonists and antagonists of the cannabinoid receptors, inhibitors of endocannabinoid hydrolysis, and cannabinoid analogs have been utilized to probe the pathways involved in the effects of the endocannabinoid system on cancer cell apoptosis, proliferation, migration, adhesion, and invasion. The antiproliferative and apoptotic effects produced by some of these pharmacological probes reveal that the endocannabinoid system is a promising new target for the development of novel chemotherapeutics to treat cancer. PMID- 22038021 TI - Molecular characterization and mRNA expression of carbamoyl phosphate synthetase III in the liver of the African lungfish, Protopterus annectens, during aestivation or exposure to ammonia. AB - This study aimed to obtain the full sequence of carbamoyl phosphate synthetase III (cps III) from, and to determine the mRNA expression of cps III in, the liver of P. annectens during aestivation in air, hypoxia or mud, or exposure to environmental ammonia (100 mmol l(-1) NH(4)Cl). The complete coding cDNA sequence of cps III from the liver of P. annectens consisted of 4530 bp, which coded for 1,510 amino acids with an estimated molecular mass of 166.1 kDa. The Cps III of P. annectens consisted of a mitochondrial targeting sequence of 44 amino acid residues, a GAT domain spanning from tyrosine 45 to isoleucine 414, and a methylglyoxal synthase-like domain spanning from valine 433 to arginine 1513. Two cysteine residues (cysteine 1337 and cysteine 1347) that are characteristic of N acetylglutamate dependency were also present. The critical Cys-His-Glu catalytic triad (cysteine 301, histidine 385 and glutamate 387) together with methionine 302 and glutamine 305 affirmed that P. annectens expressed Cps III and not Cps I. A comparison of the translated amino acid sequence of Cps III from P. annectens with CPS sequences from other animals revealed that it shared the highest similarity with elasmobranch Cps III. A phylogenetic analysis indicates that P. annectens CPS III could have evolved from Cps III of elasmobranchs. Indeed, Cps III from P. annectens used mainly glutamine as the substrate, and its activity decreased significantly when glutamine and ammonia were included together in the assay system. There were significant increases (9- to 12-fold) in the mRNA expression of cps III in the liver of fish during the induction phase (days 3 and 6) of aestivation in air. Aestivation in hypoxia or in mud had a delayed effect on the increase in the mRNA expression of cps III, which extended beyond the induction phase of aestivation, reiterating the importance of differentiating effects that are intrinsic to aestivation from those intrinsic to hypoxia. Furthermore, results from this study confirmed that environmental ammonia exposure led to a significant increase in the mRNA expression of cps III in the liver of P. annectens, alluding to the important functional role of urea not only as a product of ammonia detoxification but also as a putative internal cue for aestivation. PMID- 22038025 TI - Diversity and abundance of the rumen and fecal methanogens in Altay sheep native to Xinjiang and the influence of diversity on methane emissions. AB - This study aims to investigate the influence of diet roughage proportion on the methanogenic communities from the rumen and fecal samples in Altay local sheep native to Xinjiang and better understand the association of methanogenic diversity or abundance with methane emissions of the ruminants. In this study, the high roughage diet was found to cause more methane emissions for either maintenance or ad-lib group, but the total methanogenic abundance was not influenced by roughage proportion and showed no significant difference between groups. Furthermore, the denaturing gradient gel electrophoresis was conducted to reveal the difference in methanogenic diversity. Phylogenetic analysis showed that the sequences obtained were divided into three groups, affiliated to the genus of Methanobrevibacter, Methanocorpusculum and an unidentified methanogenic like group. Of these sequences, the predominant diversity from the genus of Methanobrevibacter and the unidentified methanogenic-like archaeons in the rumen was found to be significantly induced by the high roughage diet, implying that the variation of diversity at the species or strain level might have an effect on methane emissions from the rumen. Further analysis showed that five methangenic sequences from the rumen were possibly associated with the differential methane emissions. PMID- 22038026 TI - The Paenibacillus polymyxa species is abundant among hydrogen-producing facultative anaerobic bacteria in Lake Averno sediment. AB - Lake Averno sediment was used to isolate the facultative anaerobic bacteria having the potential for H(2) production. Twenty-five out of 35 isolates recovered from the sediment sample produced hydrogen under anaerobic conditions from glucose with yields ranging from 0.1 to 0.49 mol H(2)/mol glucose. Identification based on 16S rRNA gene sequence analysis revealed that most of them belong to the Firmicutes group, with a prevalence of the Paenibacillus polymyxa species. Seven distinct genomic fingerprints among the 11 P. polymyxa isolates were obtained using the random amplified polymorphic DNA (RAPD) technique. Glucose fermentation by P. polymyxa isolates was investigated. Glucose was totally consumed after 3 days of fermentation. The fermentation products were hydrogen (0.18-0.47 mol H(2)/mol glucose), ethanol (0.1-0.5 mol ethanol/mol glucose), and 2,3-butanediol (0.1 mol 2,3-butanediol/mol glucose). Lower amounts of acetic, butyric, formic, lactic, and propionic acids were detected. All metabolic data concerning P. polymyxa isolates were analyzed by cluster analysis to reveal similarities and/or differences with clustering based on RAPD profiles. Despite the high metabolic similarity among almost all P. paenibacillus isolates, results of cluster analyses of metabolic and genetic data do not match completely. PMID- 22038028 TI - Macrocorticotropinoma shrinkage and control of hypercortisolism under long-term cabergoline therapy: case report. AB - Cushing's disease is the result of chronic overproduction of ACTH by a pituitary tumor. Although the optimal treatment is surgical removal of the adenoma, medical treatment might be an option in selected cases. A 40-year old woman with Cushing's disease was treated with cabergoline, a neuromodulatory drug, for a corticotrophic macroadenoma. Treatment was initiated at a weekly dose of 0.5 mg and then, on the basis of the evolution of UFC values, adjusted until it reached 6 mg/week. With cabergoline treatment the patient was asymptomatic, the pituitary adenoma showed a significant shrinkage on MRI and urinary cortisol excretion remained within the normal range during 7 years. We show the effectiveness of cabergoline in maintaining long-term biochemical control of hypercortisolism with significant reduction and stabilization of macroadenoma volume in a patient with Cushing's disease. PMID- 22038027 TI - Characterization of Epstein-Barr virus gp350/220 gene variants in virus isolates from gastric carcinoma and nasopharyngeal carcinoma. AB - To characterize the sequence variation of the gp350/220 and explore its potential association with EBV-associated tumors, the gp350/220 gene was sequenced from 41 EBV-associated gastric carcinoma (EBVaGC) and 81 nasopharyngeal carcinoma (NPC) biopsies as well as 35 throat washing (TW) samples from healthy donors. Preferential linkages between variants of the N-terminus of gp350/220 and EBNA3C variants were detected, and type A/BLLF1-a was the dominant variant in this study. The dominant variant in the C-terminal region of gp350/220 was 9P. The similar distribution of gp350/220 variants in NPC, EBVaGC and healthy donors suggest that gp350/220 variations are geographically restricted rather than tumor specific polymorphisms. PMID- 22038029 TI - Isolated GHD: investigation and implication of JAK/STAT related genes before and after rhGH treatment. AB - Isolated GH deficiency (IGHD) is a rare disorder that occurs as an idiopathic form in most cases. The pathway JAK/STAT promotes cellular growth and it could be implicated in this condition. In order to characterize IGHD in the pediatric population and identify genes differently expressed before and after GH therapy, we performed a quantitative evaluation of 84 genes related to the JAK/STAT pathway which, by promoting cellular growth. RT(2) Profiler PCR Array and the other/subsequent evaluations were performed in three children with severe IGHD before and after 6 months of GH therapy and in three matched normal children. Gene profiling was modified by the IGHD status and the GH therapy, with a modulation of GHR and some inflammatory genes such as CRP. We found a heterozygous nonsense mutation R43X in the GHR gene in two out of three IGHD subjects, despite a good response to therapy. After therapy cardiovascular markers linked to genes as IL6, IL8 and TNF-alpha displayed a trend toward reduction. Pre- and post therapy status differently affects gene expression. Mutational screening of GHR may be useful in investigating IGHD's etiology. Genes linked to inflammation suggest to evaluate cardiovascular risks also in pediatric IGHD subjects. PMID- 22038030 TI - The metabolic consequences of thyroxine replacement in adult hypopituitary patients. AB - The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database) were studied before and after 2 years of GH replacement. CH patients (CH, n = 1080) were compared with TSH sufficient patients (TSHsuff n = 515) as one group and divided by thyroxine dose/kg/day into tertiles (CHlow-mid-high). Anthropometry, fasting glucose, glycosylated haemoglobin (HbA1c), blood pressure, lipids, IGF-I SDS, quality of life and morbidity were studied. Analyses were standardized for gender, age, number and types of pituitary insufficiencies, stimulated GH peak, age at GH deficiency onset, aetiologies and, when appropriate, for weight and GH dose. At baseline, TSHsuff patients did not differ from CH or CHmid in any outcome. CHlow (<= 1.18 MUg thyroxine/kg/day) had increased weight, BMI and larger waist circumference (WC), CHhigh (>= 1.58 MUg thyroxine/kg/day) had lower weight, BMI, WC and IGF-I than TSHsuff and compared to their predicted weights, BMIs and WCs. For every 0.1 MUg/kg/day increase of thyroxine dose, body weight decreased 1.0 kg, BMI 0.3 kg/m(2), and WC 0.65 cm. The GH sensitivity of the CH group was higher (0.76 +/- 0.56 SDS/mg GH) than that of TSHsuff patients (0.58 +/ 0.64 SDS/mg GH), P < 0.001. The middle thyroxine dose (1.19-1.57 MUg/kg/day) seems to be the most physiological. This is equivalent to 70, 100, 125 MUg thyroxine/day for hypopituitary patients of 50, 70 or 90 kg weight, respectively. PMID- 22038031 TI - Aneurysmal subarachnoid hemorrhage (aSAH) results in low prevalence of neuro endocrine dysfunction and NOT deficiency. AB - Neuro-endocrine deficiencies have been argued to be common sequelae after aneurysmal subarachnoid hemorrhage (aSAH). As this, however, does not resemble our clinical experience, we studied the incidence of neuro-endocrine and neuropsychological deficits after aSAH. Twenty-six patients (20 females) were prospectively screened for neuro-endocrine and neuropsychological deficits 3, 6 and 12 months after aSAH. GH, IGF-1, prolactin, LH, FSH, estradiol, testosterone, ACTH as well as cortisol during ACTH-stimulation were assessed. Neuropsychological analysis covered verbal comprehension, short term and working memory, visuospatial construction, figural memory, psychomotor speed, attention, and concentration. During the study period 5 individuals demonstrated neuro endocrine dysfunction. Hypogonadotrophic hypogonadism resolved spontaneously in 2 patients and central hypothyroidism in one of these patients during the study. After 12 months three patients presented low IGF-1 levels. 73.9% of our cohort was affected by neuropsychological deficits during follow-up. At 3, 6 and 12 months the prevalences were 56.5, 52.6 and 42.1%, respectively. Interestingly, all patients with neuro-endocrine dysfunction presented impaired clinical outcome with a GOS 4 at some time point of the study (GOS 4 vs. 5, 45.5% vs. 0, P = 0.007). We found a low prevalence of neuro-endocrine and a high prevalence of neuropsychological deficits in patients 3, 6 and 12 months after aSAH without significant interrelation. Spontaneous recovery of neuro-endocrine alterations most likely presents an adaption to or dysfunction after severe illness. This hypothesis is strengthened by the fact that only patients with inferior clinical outcome after aSAH as assessed by GOS demonstrated neuro-endocrine dysfunction. PMID- 22038032 TI - The anterior skull base nasal inventory (ASK nasal inventory): a clinical tool for evaluating rhinological outcomes after endonasal surgery for pituitary and cranial base lesions. AB - The goal of this project was to develop a prospectively-validated, site-specific patient quality of life survey for assessing nasal outcomes following endonasal pituitary and skull base surgery. (ClinicalTrials.gov #NCT01322945) An 9-item patient survey (the ASK Nasal Inventory) focusing on the most common postoperative complaints, such as crusting, sinusitis, pain, and ease of breathing, was developed by the anterior skull base team at the Barrow Neurological Institute. Content was validated in structured patient interviews and by four subject matter experts. This survey was self-administered before and 3 months after surgery to 94 patients (52 endonasal surgery and 42 controls) between October 2010 and June 2011. Standard methods for psychometric evaluation were applied. Cronbach's alpha was 0.83 indicating good internal consistency. Test-retest reliability was excellent in both groups (r = 0.87 and 0.95; P < 0.001). Discriminant validity was determined by comparing mean scores at 3 months in the endonasal and control groups and the difference was significant (13.5 vs. 17.2, P = 0.001). Standardized response mean was 0.17 suggesting that the scale was sensitive to clinical change. Concurrent validity was determined by mean ASK Nasal score for each level of self-reported overall functioning at 3 months (P = 0.001). Preliminary psychometric evaluation of the performance of the ASK Nasal Inventory suggests that it meets criteria as a clinical and research instrument in endonasal surgery. This study also suggests modifications to the instrument, which will serve as key quality of life endpoint in an ongoing multicenter nasal outcomes study. PMID- 22038033 TI - Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of giant pituitary adenomas. AB - Giant (>4 cm) pituitary macroadenomas often require surgery to decompress the optic nerves. Compared with traditional open or transsphenoidal microscopic methods, the extended endoscopic endonasal transsphenoidal approach offers the potential for aggressive resection via a minimal access corridor. We conducted a systematic review of the literature to further our understanding of the role of endoscopy in the management of these challenging lesions. MEDLINE search of the modern literature (1995-2010) to identify surgical series for pediatric and adult pituitary adenomas >4 cm in maximal diameter. Patient and tumor characteristics, resection, morbidity and visual outcome were compared by approach. Chi-square and Fisher's exact tests with post-hoc Bonferroni analysis were used for statistical analyses. Sixteen studies (478 patients) were included. Compared with the open cohort, the endoscopic cohort had higher rates of gross total resection (47.2% vs. 9.6%; P < 0.003) and improved visual outcome (91.1% vs. 45.7%; P < 0.003). The microscopic transsphenoidal cohort had lower rate of total resection and worse visual outcomes than the endoscopic group. There were no instances of postoperative CSF leak reported in the endoscopic group. The transcranial group had a higher rate perioperative mortality compared to the transsphenoidal group (P = 0.004). In select cases, the endoscopic endonasal approach is safe and effective for the treatment of giant pituitary adenomas, with the potential for gross total resection and improved visual outcome. CSF leak, which is a major limitation of the endonasal approach, may be avoided using meticulous multi-layer closure and vascularised nasoseptal flaps. PMID- 22038036 TI - Host identity impacts rhizosphere fungal communities associated with three alpine plant species. AB - Fungal diversity and composition are still relatively unknown in many ecosystems; however, host identity and environmental conditions are hypothesized to influence fungal community assembly. To test these hypotheses, we characterized the richness, diversity, and composition of rhizosphere fungi colonizing three alpine plant species, Taraxacum ceratophorum, Taraxacum officinale, and Polemonium viscosum. Roots were collected from open meadow and willow understory habitats at treeline on Pennsylvania Mountain, Colorado, USA. Fungal small subunit ribosomal DNA was sequenced using fungal-specific primers, sample-specific DNA tags, and 454 pyrosequencing. We classified operational taxonomic units (OTUs) as arbuscular mycorrhizal (AMF) or non-arbuscular mycorrhizal (non-AMF) fungi and then tested whether habitat or host identity influenced these fungal communities. Approximately 14% of the sequences represented AMF taxa (44 OTUs) with the majority belonging to Glomus groups A and B. Non-AMF sequences represented 186 OTUs belonging to Ascomycota (58%), Basidiomycota (26%), Zygomycota (14%), and Chytridiomycota (2%) phyla. Total AMF and non-AMF richness were similar between habitats but varied among host species. AMF richness and diversity per root sample also varied among host species and were highest in T. ceratophorum compared with T. officinale and P. viscosum. In contrast, non-AMF richness and diversity per root sample were similar among host species except in the willow understory where diversity was reduced in T. officinale. Fungal community composition was influenced by host identity but not habitat. Specifically, T. officinale hosted a different AMF community than T. ceratophorum and P. viscosum while P. viscosum hosted a different non-AMF community than T. ceratophorum and T. officinale. Our results suggest that host identity has a stronger effect on rhizosphere fungi than habitat. Furthermore, although host identity influenced both AMF and non-AMF, this effect was stronger for the mutualistic AMF community. PMID- 22038035 TI - The bacterial community associated with the marine polychaete Ophelina sp.1 (Annelida: Opheliidae) is altered by copper and zinc contamination in sediments. AB - Tolerant species of polychaete worms can survive in polluted environments using various resistance mechanisms. One aspect of resistance not often studied in polychaetes is their association with symbiotic bacteria, some of which have resistance to metals and may help the organism to survive. We used "next generation" 454 sequencing of bacterial 16S rRNA sequences associated with polychaetes from a copper- and zinc-polluted harbor and from a reference site to determine bacterial community structure. We found changes in the bacteria at the polluted site, including increases in the abundance of bacteria from the order Alteromonadales. These changes in the bacteria associated with polychaetes may be relatively easy to detect and could be a useful indicator of metal pollution. PMID- 22038037 TI - Osmotic shock augments ethanol stress in Saccharomyces cerevisiae MTCC 2918. AB - Yeast cells sense and respond to hypertonicity. Saccharomyces cerevisiae MTCC 2918 was tested for its metabolic status in 1 M NaCl by cell viability analysis, intracellular glycerol content and total antioxidant capacity. Yeast cell viability was maximum in 1 M NaCl and 24 h addition of 1 M NaCl was effective in induction of hyperosmolarity. Increased glycerol contents in cells treated with salt indicated adaptation to osmotic stress with a maximum of 240.87 +/- 0.38 mg/g dry weight (DW) at 72 h. The total antioxidant status with 1 M NaCl was 9.29 +/- 0.39 mM/g DW at 96 h reflecting free radical quenching to overcome stress with increasing growth period. Considering that pre-adaptation to one type of stress evoked a protective response to other stress factors, we have attempted the cross adaptation of osmotic shock to high ethanol concentrations. In effect, we observed that osmotic shock lowered the cell survival by augmentation of cell toxicity by ethanol due to stress induction during exponential phase. Glycerol accumulation to an order of 470.27 +/- 0.53 mg/g DW at 48 h in 1 M NaCl and 12% ethanol indicated that both stresses culminated in membrane disruption further leading to cell burst and contributed to the stress overload. PMID- 22038034 TI - The effect of resource islands on abundance and diversity of bacteria in arid soils. AB - Bacteria and nutrients were determined in upper soil samples collected underneath and between canopies of the dominant perennial in each of three sites along a steep precipitation gradient ranging from the Negev desert in the south of Israel to a Mediterranean forest in the north. Bacterial abundance, monitored by phospholipid fatty acid analysis, was significantly higher under the shrub canopy (compared to barren soils) in the arid and semi-arid sites but not in the Mediterranean soils. Bacterial community composition, determined using terminal restriction fragment length polymorphism and clone libraries, differed according to the sample's origin. Closer examination revealed that in the arid and semi arid sites, alpha-Proteobacteria are more abundant under the shrub canopy, while barren soils are characterized by a higher abundance of Actinobacteria. The bacterial communities in the Mediterranean soils were similar in both patch types. These results correspond to the hypothesis of "resource islands", suggesting that shrub canopies provide a resource haven in low-resource landscapes. Yet, a survey of the physicochemical parameters of inter- and under shrub soils could not attribute the changes in bacterial diversity to soil moisture, organic matter, or essential macronutrients. We suggest that in the nutrient-poor soils of the arid and semi-arid sites, bacteria occupying the soil under the shrub canopy may have longer growth periods under favorable conditions, resulting in their increased biomass and altered community composition. PMID- 22038038 TI - Construction of gene library of 20 kb DNAs from parasporal crystal in Bacillus thuringiensis Strain 4.0718: phylogenetic analysis and molecular docking. AB - The 20 kb DNAs are associated with crystals in many subspecies of Bacillus thuringiensis. We isolated 20 kb DNAs from crystals of B. thuringiensis strain 4.0718, then constructed a gene library using DNA fragments of Sau3AI partial digestion and pbluescriptIISK(+) vector. We screened out 440 recombinants, yielding a genomic coverage of ten and including 99% sequence of DNA which achieved the required theoretical value to construct the gene library. Through NCBI Blast and homology analysis, the sequencing results proved that the DNA came from the chromosome of B. thuringiensis. Moreover, we have completed the multiple alignment of homologous ropB protein sequences and phylogenetic analysis using bioinformatic software. For further investigation of the interactions between 20 kb DNAs and protoxins, molecular docking has also been done. PMID- 22038039 TI - Photosensitizer-doped conjugated polymer nanoparticles for simultaneous two photon imaging and two-photon photodynamic therapy in living cells. AB - Photosensitizer doped conjugated polymer nanoparticles have been prepared by incorporating polyoxyethylene nonylphenylether (CO-520) into the nanoparticles using a re-precipitation method. The conjugated polymer, poly[9,9 dibromohexylfluorene-2,7-ylenethylene-alt-1,4-(2,5-dimethoxy)phenylene] (PFEMO), was used as the host matrix to disperse tetraphenylporphyrin (TPP) and an energy donor to enhance the two-photon excitation properties of TPP. These CO-520 incorporated, TPP-doped PFEMO nanoparticles are stable and have low cytotoxicity in the dark. The TPP emission of the nanoparticles was found to be enhanced by about 20 times by PFEMO under two-photon excitation. The nanoparticles showed significantly enhanced two-photon excitation singlet oxygen generation efficiency and two-photon photodynamic therapy activity in cancer cells. These composite nanoparticles display features required for ideal photosensitizers, such as low cytotoxicity in the dark and efficient two-photon photodynamic activity under laser radiation. In addition, these novel nano-photosensitizers allow simultaneous in vivo monitoring by two-photon fluorescence imaging during two photon photodynamic treatment. These photosensitizer-doped conjugated polymer nanoparticles can act as novel photosensitizing agents for two-photon photodynamic therapy and related applications. PMID- 22038040 TI - Shh signaling is essential for rugae morphogenesis in mice. AB - Palatal ridges, or rugae palatinae, are corrugated structures observed in the hard palate region. They are found in most mammalian species, but their number and arrangement are species-specific. Nine palatal rugae are found in the mouse secondary palate. Previous studies have shown that epithelial Shh signaling in the palatal ridge plays an important role during rugae development. Moreover, Wnt family members, including LEF1, play a functional role in orofacial morphogenesis. To explore the function of Shh during rugae development, we utilized the maternal transfer of 5E1 (anti-Shh antibody) to mouse embryos. 5E1 induced abnormal rugae patterning characterized by a spotted shape of palatal ridge rather than a stripe. The expression patterns of Shh and Shh-related genes, Sostdc1, Lef1 and Ptch1, were disrupted following 5E1 injection. Moreover, rugae specific cell proliferation and inter-rugae-specific apoptosis were affected by inhibition of Shh signaling. We hypothesize that the altered gene expression patterns and the change in molecular events caused by the inhibition of Shh signaling may have induced abnormal rugae patterning. Furthermore, we propose a reaction-diffusion model generated by Wnt, Shh and Sostdc1 signaling. In this study, we show that Sostdc1, a secreted inhibitor of the Wnt pathway, is a downstream target of Shh and hypothesize that the interaction of Wnt, Shh and Sostdc1 is a pivotal mechanism controlling the spatial patterning of palatal rugae. PMID- 22038041 TI - Evaluation of CAG repeat length of androgen receptor expressing cells in human testes showing different pictures of spermatogenic impairment. AB - The androgen receptor (AR) is a ligand-activated transcriptional factor with crucial importance for spermatogenesis. Its transactivation domain consists of a polymorphic sequence of 9-36 cytosin-adenin-guanin (CAG) repeats. Within the physiological range an increased CAG repeat length is assumed to correlate with the reduced androgen sensitivity resulting in impaired spermatogenesis. In 33 testes of 32 patients showing different histological pictures ranging from normal spermatogenesis, hypospermatogenesis to severe spermatogenetic impairment such as maturation arrest, Sertoli cell only Syndrome (SCO) and mixed atrophy, CAG repeat length was assessed in lymphocyte DNA, DNA/mRNA from testis homogenate and in mRNA of AR expressing Sertoli cells within the seminiferous tubules, and interstitial Leydig cells collected by the laser-assisted cell picking. The latter examination was performed to detect a possible somatic mosaicism of CAG repeat length in different testicular cell populations. CAG repeat lengths varied from 12 to 27 repeats, i.e., within the physiological range. We found deviating CAG repeat numbers in different fractions of AR expressing Sertoli and Leydig cells indicating tissue heterogeneity. We did not find a correlation of CAG repeat length to testicular histology or AR expression, and testosterone or luteinizing hormone levels even in biopsies showing mixed atrophy. Additionally, we evaluated the expression pattern of the AR-dependent gene androgen binding protein (ABP), and did not find a correlation to CAG repeat, but a significant reduction of ABP mRNA related to severe spermatogenic impairment in the monomorphic histologies. These data suggest other factors than CAG repeat to be responsible for severe spermatogenic impairment including mixed atrophy. PMID- 22038042 TI - Dictyostelium puromycin-sensitive aminopeptidase A is a nucleoplasmic nucleomorphin-binding protein that relocates to the cytoplasm during mitosis. AB - Nucleomorphin (NumA1) is a nucleolar/nucleoplasmic protein linked to cell cycle in Dictyostelium. It interacts with puromycin-sensitive aminopeptidase A (PsaA) which in other organisms is a Zn(2+)-metallopeptidase thought to be involved in cell cycle progression and is involved in several human diseases. Here, we have shown that Dictyostelium PsaA contains domains characteristic of the M1 family of Zn(2+)-metallopeptidases: a GAMEN motif and a Zn(2+)-binding domain. PsaA colocalized with NumA1 in the nucleoplasm in vegetative cells and was also present to a lesser extent in the cytoplasm. The same localization pattern was observed in cells from slugs, however, in fruiting bodies PsaA was only detected in spore nuclei. During mitosis PsaA redistributed mainly throughout the cytoplasm. It possesses a functional nuclear localization signal ((680)RKRF(683)) necessary for nuclear entry. To our knowledge, this is the first nuclear localization signal identified in a Psa from any organism. Treatment with Ca(2+) chelators or calmodulin antagonists indicated that neither Ca(2+) nor calmodulin is involved in PsaA localization. These results are interpreted in terms of the inter-relationship between NumA1 and PsaA in cell function in Dictyostelium. PMID- 22038043 TI - Evaluation of myelin sheath and collagen reorganization pattern in a model of peripheral nerve regeneration using an integrated histochemical approach. AB - Peripheral nerves are complex histological structures that can be affected by a variety of conditions with different degree of axonal degeneration and demyelination. For the study of peripheral nerve regeneration in pathology and tissue engineering, it is necessary to evaluate the regeneration, remyelination and extracellular matrix reorganization of the neural tissue. Currently, different histochemical techniques must be used in parallel, and a correlation among their findings should be further performed. In this work, we describe a new histochemical method for myelin and collagen fibers based on luxol fast blue and picrosirius methods, for the evaluation of the morphology, the myelin sheath and the collagen fiber reorganization using a model of peripheral nerve regeneration. Whole brain, normal sciatic nerve and regenerating peripheral nerve samples were fixed in 10% neutral buffered formalin and paraffin-embedded, for the performance of the hematoxylin-eosin stain, the Luxol fast blue method and the new histochemical method for myelin and collagen. The results of this technique revealed that this new histochemical method allowed us to properly evaluate histological patterns, and simultaneously observe the histochemical reaction for myelin sheath and collagen fibers in normal tissue, and during the regeneration process. In conclusion, this new method combines morphological and histochemical properties that allowed us to determine with high accuracy the degree of remyelination and collagen fibers reorganization. For all these reasons, we hypothesize that this new histochemical method could be useful in pathology and tissue engineering. PMID- 22038044 TI - Expression of DDX25 in nuage components of mammalian spermatogenic cells: immunofluorescence and immunoelectron microscopic study. AB - The localization of DDX25/GRTH and gonadotropin-stimulated RNA helicase was studied in the spermatogenic cells of rat, mouse, and guinea pig by immunofluorescence and immunoelectron microscopy (IEM). Immunofluorescence studies identified four kinds of granular staining: (1) fine particles observed in meiotic cells; (2) small granules associated with a mitochondrial marker, appearing in pachytene spermatocytes after stage V; (3) short strands lacking the mitochondrial marker in late spermatocytes; and, (4) large irregularly shaped granules in round spermatids. IEM identified DDX25 signals in nine compartments: (1) fine dense particles in the meiotic cells; (2) intermitochondrial cement; (3) loose aggregates of 70-90 nm particles; (4) chromatoid bodies; (5) late chromatoid bodies; (6) satellite bodies; (7) granulated bodies; (8) mitochondria associated granules; and, (9) reticulated bodies. Compartments (1) to (6) were previously classified into nuage while (7) to (9) were classified as nuage components by the present study. The results suggest that DDX25 functions in these nine compartments. PMID- 22038045 TI - Reproductive decision-making and periconception practices among HIV-positive men and women attending HIV services in Durban, South Africa. AB - Understanding reproductive decisions and periconception behavior among HIV discordant couples is important for designing risk reduction interventions for couples who choose to conceive. In-depth interviews were conducted to explore reproductive decision-making and periconception practices among HIV-positive women with recent pregnancy (n = 30), and HIV-positive men (n = 20), all reporting partners of negative or unknown HIV-status, and attending HIV services in Durban, South Africa. Transcripts were coded for categories and emergent themes. Participants expressed strong reasons for having children, but rarely knew how to reduce periconception HIV transmission. Pregnancy planning occurred on a spectrum ranging from explicitly intended to explicitly unintended, with many falling in between the two extremes. Male fertility desire and misunderstanding serodiscordance contributed to HIV risk behavior. Participants expressed openness to healthcare worker advice for safer conception and modified risk behavior post-conception, suggesting the feasibility of safer conception interventions which may target both men and women and include serodiscordance counseling and promotion of contraception. PMID- 22038046 TI - Off the beaten paths: alternative and crosstalk regulation of Rho GTPases. AB - Rho proteins are small GTPases of the Ras superfamily that regulate a wide variety of biological processes, ranging from gene expression to cell migration. Mechanistically, the major Rho GTPases function as molecular switches cycling between an inactive GDP-bound and an active GTP-bound conformation, although several Rho proteins spontaneously exchange nucleotides or are simply devoid of GTPase activity. For over a decade, RhoGEFs and RhoGAPs have been established as the mainstream regulators of Rho proteins, respectively flipping the switch on or off. However, regulation by GEFs and GAPs leaves several fundamental questions on the operation of the Rho switch unanswered, indicating that the regulation of Rho proteins does not rely exclusively on RhoGEFs and RhoGAPs. Recent evidence indeed suggests that Rho GTPases are finely tuned by multiple alternative regulatory mechanisms, including post-translational modifications and protein degradation, as well as crosstalk mechanisms between Rho proteins. Here we review these alternative mechanisms and discuss how they alter Rho protein function and signaling. We also envision how the classic binary Rho switch may indeed function more like a switchboard with multiple switches and dials that can all contribute to the regulation of Rho protein function. PMID- 22038047 TI - Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non small-cell lung cancer cells. AB - Metformin causes an AMP/ATP ratio increase and AMP-activated protein kinase (AMPK) activation. Since caveolin-1 (Cav-1) plays a role in AMPK activation and energy balance, we investigated whether Cav-1 could participate in metformin's inhibitory effect on IGF1 signaling. The effect of metformin was studied in two non-small-cell lung cancer (NSCLC) cell lines, Calu-1 and Calu-6, expressing higher and lower amounts of Cav-1, respectively. In Calu-1, but not in Calu-6 cells, metformin reduced phosphorylation of type 1 insulin-like growth factor receptor (IGF-IR) substrates Akt and Forkhead transcription factor 3a (FOXO3a), inhibited IGF1-dependent FOXO3a nuclear exit, and decreased IGF1-dependent cell proliferation. Here, we show that sensitivity of NSCLC cells to metformin was dependent on Cav-1 expression and that metformin required Cav-1 to induce AMPK phosphorylation and AMP/ATP ratio increase. Cav-1 silencing in Calu-1 and overexpression in Calu-6 reduced and improved, respectively, the inhibitory effect of metformin on IGF1-dependent Akt phosphorylation. Prolonged metformin treatment in Calu-6 cells induced a dose-dependent expression increase of Cav-1 and OCT1, a metformin transporter. Cav-1 and OCT1 expression was associated with the antiproliferative effect of metformin in Calu-6 cells (IC(50)=18 mM). In summary, these data suggest that Cav-1 is required for metformin action in NSCLC cells. PMID- 22038048 TI - Down-regulation of glutatione S-transferase alpha 4 (hGSTA4) in the muscle of thermally injured patients is indicative of susceptibility to bacterial infection. AB - Patients with severe burns are highly susceptible to bacterial infection. While immunosuppression facilitates infection, the contribution of soft tissues to infection beyond providing a portal for bacterial entry remains unclear. We showed previously that glutathione S-transferase S1 (gstS1), an enzyme with conjugating activity against the lipid peroxidation byproduct 4-hydroxynonenal (4HNE), is important for resistance against wound infection in Drosophila muscle. The importance of the mammalian functional counterpart of GstS1 in the context of wounds and infection has not been investigated. Here we demonstrate that the presence of a burn wound dramatically affects expression of both human (hGSTA4) and mouse (mGsta4) 4HNE scavengers. hGSTA4 is down-regulated significantly within 1 wk of thermal burn injury in the muscle and fat tissues of patients from the large-scale collaborative Inflammation and the Host Response to Injury multicentered study. Similarly, mGsta4, the murine GST with the highest catalytic efficiency for 4HNE, is down-regulated to approximately half of normal levels in mouse muscle immediately postburn. Consequently, 4HNE protein adducts are increased 4- to 5-fold in mouse muscle postburn. Using an open wound infection model, we show that deletion of mGsta4 renders mice more susceptible to infection with the prevalent wound pathogen Pseudomonas aeruginosa, while muscle hGSTA4 expression negatively correlates with burn wound infection episodes per patient. Our data suggest that hGSTA4 down-regulation and the concomitant increase in 4HNE adducts in human muscle are indicative of susceptibility to infection in individuals with severely thermal injuries. PMID- 22038049 TI - Neuritogenesis: the prion protein controls beta1 integrin signaling activity. AB - Cytoskeleton modifications are required for neuronal stem cells to acquire neuronal polarization. Little is known, however, about mechanisms that orchestrate cytoskeleton remodeling along neuritogenesis. Here, we show that the silencing of the cellular prion protein (PrP(C)) impairs the initial sprouting of neurites upon induction of differentiation of the 1C11 neuroectodermal cell line, indicating that PrP(C) is necessary to neuritogenesis. Such PrP(C) function relies on its capacity to negatively regulate the clustering, activation, and signaling activity of beta1 integrins at the plasma membrane. beta1 Integrin aggregation caused by PrP(C) depletion triggers overactivation of the RhoA-Rho kinase-LIMK-cofilin pathway, which, in turn, alters the turnover of focal adhesions, increases the stability of actin microfilaments, and in fine impairs neurite formation. Inhibition of Rho kinases is sufficient to compensate for the lack of PrP(C) and to restore neurite sprouting. We also observe an increased secretion of fibronectin in the surrounding milieu of PrP(C)-depleted 1C11 cells, which likely self-sustains beta1 integrin signaling overactivation and contributes to neuritogenesis defect. Our overall data reveal that PrP(C) contributes to the acquisition of neuronal polarization by modulating beta1 integrin activity, cell interaction with fibronectin, and cytoskeleton dynamics. PMID- 22038050 TI - Dietary fructose inhibits lactation-induced adaptations in rat 1,25-(OH)2D3 synthesis and calcium transport. AB - We recently showed that excessive fructose consumption, already associated with numerous metabolic abnormalities, reduces rates of intestinal Ca(2+) transport. Using a rat lactation model with increased Ca(2+) requirements, we tested the hypothesis that mechanisms underlying these inhibitory effects of fructose involve reductions in renal synthesis of 1,25-(OH)(2)D(3). Pregnant and virgin (control) rats were fed isocaloric fructose or, as controls, glucose, and starch diets from d 2 of gestation to the end of lactation. Compared to virgins, lactating dams fed glucose or starch had higher rates of intestinal transcellular Ca(2+) transport, elevated intestinal and renal expression of Ca(2+) channels, Ca(2+)-binding proteins, and CaATPases, as well as increased levels of 25 (OH)D(3) and 1,25-(OH)(2)D(3). Fructose consumption prevented almost all of these lactation-induced increases, and reduced vitamin D receptor binding to promoter regions of Ca(2+) channels and binding proteins. Changes in 1,25-(OH)(2)D(3) level were tightly correlated with alterations in expression of 1alpha hydroxylase but not with levels of parathyroid hormone and of 24-hydroxylase. Bone mineral density, content, and mechanical strength each decreased with lactation, but then fructose exacerbated these effects. When Ca(2+) requirements increase during lactation or similar physiologically challenging conditions, excessive fructose consumption may perturb Ca(2+) homeostasis because of fructose induced reductions in synthesis of 1,25-(OH)(2)D(3). PMID- 22038053 TI - An unusual complication related to acupuncture point catgut embedding treatment of obesity. AB - Treatment of obesity by embedding catgut in acupuncture points has a satisfactory therapeutic effect in many patients. Even though results of its effectiveness are mixed, serious complications are rarely reported with this Chinese traditional therapy. Here an unusual complication of the treatment is reported: multiple tender subcutaneous nodules developed where the catgut was embedded over the lower abdomen and both medial thighs 1 month after treatment. Clinicians should be alert to this possible cause of a rather strange presenting physical sign. PMID- 22038052 TI - Allele-specific siRNA knockdown as a personalized treatment strategy for vascular Ehlers-Danlos syndrome in human fibroblasts. AB - The vascular type of the Ehlers-Danlos syndrome (vEDS) is caused by dominant negative mutations in the procollagen type III (COL3A1) gene. Patients with this autosomal dominant disorder have a shortened life expectancy due to complications from ruptured vessels or hollow organs. We tested the effectiveness of allele specific RNA interference (RNAi) to reduce the mutated phenotype in fibroblasts. Small-interfering RNAs (siRNAs) discriminating between wild-type and mutant COL3A1 allele were identified by a luciferase reporter gene assay and in primary fibroblasts from a normal donor and a patient with vEDS. The best discriminative siRNA with the mutation at position 10 resulted in >90% silencing of the mutant allele without affecting the wild-type allele. Transmission and immunogold electron microscopy of extracted extracellular matrices from untreated fibroblasts of the patient with vEDS revealed structurally abnormal fibrils. After siRNA treatment, collagen fibrils became similar to fibrils from fibroblasts of normal and COL3A1 haploinsufficient donors. In addition, it was shown that expression of mutated COL3A1 activates the unfolded protein response and that reduction of the amount of mutated protein by siRNA reduces cellular stress. Taken together, the results provide evidence that allele-specific siRNAs are able to reduce negative effects of mutated COL3A1 proteins. Thus, the application of allele-specific RNAi may be a promising direction for future personalized therapies to reduce the severity of vEDS. PMID- 22038051 TI - Peptides derived from the prohormone proNPQ/spexin are potent central modulators of cardiovascular and renal function and nociception. AB - Computational methods have led two groups to predict the endogenous presence of a highly conserved, amidated, 14-aa neuropeptide called either spexin or NPQ. NPQ/spexin is part of a larger prohormone that contains 3 sets of RR residues, suggesting that it could yield more than one bioactive peptide; however, no in vivo activity has been demonstrated for any peptide processed from this precursor. Here we demonstrate biological activity for two peptides present within proNPQ/spexin. NPQ/spexin (NWTPQAMLYLKGAQ-NH(2)) and NPQ 53-70 (FISDQSRRKDLSDRPLPE) have differing renal and cardiovascular effects when administered intracerebroventricularly or intravenously into rats. Intracerebroventricular injection of NPQ/spexin produced a 13 +/- 2 mmHg increase in mean arterial pressure, a 38 +/- 8 bpm decrease in heart rate, and a profound decrease in urine flow rate. Intracerebroventricular administration of NPQ 53-70 produced a 26 +/- 9 bpm decrease in heart rate with no change in mean arterial pressure, and a marked increase in urine flow rate. Intraventricular NPQ/spexin and NPQ 53-70 also produced antinociceptive activity in the warm water tail withdrawal assay in mice (ED(50)<30 and 10 nmol for NPQ/spexin and NPQ 53-70, respectively). We conclude that newly identified peptides derived from the NPQ/spexin precursor contribute to CNS-mediated control of arterial blood pressure and salt and water balance and modulate nociceptive responses. PMID- 22038054 TI - Infantile colic: exploring the potential role of maternal acupuncture. AB - Lack of knowledge about the pathophysiology of infantile colic limits the development of effective drugs and treatment modalities including acupuncture. Acupuncture research has targeted the baby without considering the mother. However, the pathophysiological clues indicate that infantile colic is a shared pathology between the mother and the baby, especially in the case of breastfeeding mothers. A new theory proposed in this paper involves levels of the cytokine tumour necrosis factor alpha in the mother's milk and its influences on melatonin and serotonin metabolism in the baby as major components of the pathophysiology of infantile colic. These can be normalised by applying acupuncture to the breastfeeding mother alone or also to the baby. PMID- 22038055 TI - The role of glutamate dehydrogenase in mammalian ammonia metabolism. AB - Glutamate dehydrogenase (GDH) catalyzes the reversible inter-conversion of glutamate to alpha-ketoglutarate and ammonia. High levels of GDH activity is found in mammalian liver, kidney, brain, and pancreas. In the liver, GDH reaction appears to be close-to-equilibrium, providing the appropriate ratio of ammonia and amino acids for urea synthesis in periportal hepatocytes. In addition, GDH produces glutamate for glutamine synthesis in a small rim of pericentral hepatocytes. Hence, hepatic GDH can be either a source for ammonia or an ammonia scavenger. In the kidney, GDH function produces ammonia from glutamate to control acidosis. In the human, the presence of two differentially regulated isoforms (hGDH1 and hGDH2) suggests a complex role for GDH in ammonia homeostasis. Whereas hGDH1 is sensitive to GTP inhibition, hGDH2 has dissociated its function from GTP control. Furthermore, hGDH2 shows a lower optimal pH than hGDH1. The hGDH2 enzyme is selectively expressed in human astrocytes and Sertoli cells, probably facilitating metabolic recycling processes essential for their supportive role. Here, we report that hGDH2 is also expressed in the epithelial cells lining the convoluted tubules of the renal cortex. As hGDH2 functions more efficiently under acidotic conditions without the operation of the GTP energy switch, its presence in the kidney may increase the efficacy of the organ to maintain acid base equilibrium. PMID- 22038056 TI - Novel role of NADPH oxidase in ischemic myocardium: a study with Nox2 knockout mice. AB - Several potential sources of reactive oxygen species (ROS) in cells exist. One source is NADPH oxidase, which is especially important for superoxide radical production. Nox2 is a primary regulatory subunit of NADPH oxidase. In the present study, we examined the role of ROS and NADPH oxidase in ischemic preconditioning (IP)-mediated cardioprotection by using Nox2(-/-) mice. Both wild-type (WT) and Nox2(-/-) mice were subjected to either 30 min of ischemia followed by 2 h of reperfusion (IR) or IP prior to 30 min ischemia and 2 h of reperfusion. Reduction in left ventricular developed pressure (60.1 versus 63 mmHg), dp/dt (max) (893 versus 1,027 mmHg/s), and aortic flow (0.9 versus 1.8 ml/min) was observed in Nox2(-/-)IPIR compared to WTIPIR along with increased infarct size (33% versus 22%) and apoptosis after 120 min of reperfusion. Differentially regulated genes were demonstrated by comparing gene expression in WTIPIR versus Nox2(-/-) IPIR hearts. Selected differentially regulated genes such as beta-catenin, SRPK3, ERDR1, ACIN1, Syntaxin-8, and STC1 were validated by real-time PCR. Taken together, this is the first report identifying important, differentially expressed genes during ischemic preconditioning in Nox2(-/-) mice by using microarray analysis. PMID- 22038057 TI - Palladium doping of magic gold cluster Au38(SC2H4Ph)24: formation of Pd2Au36(SC2H4Ph)24 with higher stability than Au38(SC2H4Ph)24. AB - A phenylethanethiolate-protected Pd(2)Au(36)(SC(2)H(4)Ph)(24) cluster, which is a two-Pd atom-doped cluster of the well studied magic gold cluster Au(38)(SC(2)H(4)Ph)(24), was synthesized in high purity and its stability was investigated. The results demonstrate that Pd(2)Au(36)(SC(2)H(4)Ph)(24) is more stable than Au(38)(SC(2)H(4)Ph)(24) against degradation in solution and core etching by thiols. PMID- 22038058 TI - Dietary protein restriction impairs growth, immunity, and disease resistance in southern leopard frog tadpoles. AB - The immune system is a necessary, but potentially costly, defense against infectious diseases. When nutrition is limited, immune activity may consume a significant amount of an organism's energy budget. Levels of dietary protein affect immune system function; high levels can enhance disease resistance. We exposed southern leopard frog [Lithobates sphenocephalus (=Rana sphenocephala)] tadpoles to high and low protein diets crossed with the presence or absence of the pathogenic amphibian chytrid fungus (Batrachochytrium dendrobatidis; Bd) and quantified: (1) tadpole resistance to Bd; (2) tadpole skin-swelling in response to phytohaemagglutinin (PHA) injection (a measure of the T cell-mediated response of the immune system); (3) bacterial killing ability (BKA) of tadpole blood (a measure of the complement-mediated cytotoxicity of the innate immune system); and (4) tadpole growth and development. Tadpoles raised on a low-protein diet were smaller and less developed than tadpoles on a high-protein diet. When controlled for developmental stage, tadpoles raised on a low-protein diet had reduced PHA and BKA responses relative to tadpoles on a high-protein diet, but these immune responses were independent of Bd exposure. High dietary protein significantly increased resistance to Bd. Our results support the general hypothesis that host condition can strongly affect disease resistance; in particular, fluctuations in dietary protein availability may change how diseases affect populations in the field. PMID- 22038059 TI - Effects of herbivory, nutrients, and reef protection on algal proliferation and coral growth on a tropical reef. AB - Maintaining coral reef resilience against increasing anthropogenic disturbance is critical for effective reef management. Resilience is partially determined by how processes, such as herbivory and nutrient supply, affect coral recovery versus macroalgal proliferation following disturbances. However, the relative effects of herbivory versus nutrient enrichment on algal proliferation remain debated. Here, we manipulated herbivory and nutrients on a coral-dominated reef protected from fishing, and on an adjacent macroalgal-dominated reef subject to fishing and riverine discharge, over 152 days. On both reefs, herbivore exclusion increased total and upright macroalgal cover by 9-46 times, upright macroalgal biomass by 23-84 times, and cyanobacteria cover by 0-27 times, but decreased cover of encrusting coralline algae by 46-100% and short turf algae by 14-39%. In contrast, nutrient enrichment had no effect on algal proliferation, but suppressed cover of total macroalgae (by 33-42%) and cyanobacteria (by 71% on the protected reef) when herbivores were excluded. Herbivore exclusion, but not nutrient enrichment, also increased sediment accumulation, suggesting a strong link between herbivory, macroalgal growth, and sediment retention. Growth rates of the corals Porites cylindrica and Acropora millepora were 30-35% greater on the protected versus fished reef, but nutrient and herbivore manipulations within a site did not affect coral growth. Cumulatively, these data suggest that herbivory rather than eutrophication plays the dominant role in mediating macroalgal proliferation, that macroalgae trap sediments that may further suppress herbivory and enhance macroalgal dominance, and that corals are relatively resistant to damage from some macroalgae but are significantly impacted by ambient reef condition. PMID- 22038060 TI - Ontogenetic changes in leaf traits of tropical rainforest trees differing in juvenile light requirement. AB - Relationships between leaf traits and the gap dependence for regeneration, and ontogenetic changes therein, were investigated in juvenile and adult tropical rainforest tree species. The juveniles of the 17 species included in the study were grown in high light, similar to the exposed crowns of the adult trees. The traits were structural, biomechanical, chemical and photosynthetic. With increasing species gap dependence, leaf mass per area (LMA) decreased only slightly in juveniles and remained constant in adults, whereas punch strength together with tissue density decreased, and photosynthetic capacity and chlorophyll increased. Contrary to what has been mostly found in evergreen tropical rainforest, the trade-off between investment in longevity and in productivity was evident at an essentially constant LMA. Of the traits pertaining to the chloroplast level, photosynthetic capacity per unit chlorophyll increased with gap dependence, but the chlorophyll a/b ratio showed no relationship. Adults had a twofold higher LMA, but leaf strength was on average only about 50% larger. Leaf tissue density, and chlorophyll and leaf N per area were also higher, whereas chlorophyll and leaf N per unit dry mass were lower. Ranking of the species, relationships between traits and with the gap dependence of the species were similar for juveniles and adults. However, the magnitudes of most ontogenetic changes were not clearly related to a species' gap dependence. The adaptive value of the leaf traits for juveniles and adults is discussed. PMID- 22038061 TI - Unravelling the limits to tree height: a major role for water and nutrient trade offs. AB - Competition for light has driven forest trees to grow exceedingly tall, but the lack of a single universal limit to tree height indicates multiple interacting environmental limitations. Because soil nutrient availability is determined by both nutrient concentrations and soil water, water and nutrient availabilities may interact in determining realised nutrient availability and consequently tree height. In SW Australia, which is characterised by nutrient impoverished soils that support some of the world's tallest forests, total [P] and water availability were independently correlated with tree height (r = 0.42 and 0.39, respectively). However, interactions between water availability and each of total [P], pH and [Mg] contributed to a multiple linear regression model of tree height (r = 0.72). A boosted regression tree model showed that maximum tree height was correlated with water availability (24%), followed by soil properties including total P (11%), Mg (10%) and total N (9%), amongst others, and that there was an interaction between water availability and total [P] in determining maximum tree height. These interactions indicated a trade-off between water and P availability in determining maximum tree height in SW Australia. This is enabled by a species assemblage capable of growing tall and surviving (some) disturbances. The mechanism for this trade-off is suggested to be through water enabling mass-flow and diffusive mobility of P, particularly of relatively mobile organic P, although water interactions with microbial activity could also play a role. PMID- 22038062 TI - Case-based knowledge and ethics education: improving learning and transfer through emotionally rich cases. AB - Case-based instruction is a stable feature of ethics education, however, little is known about the attributes of the cases that make them effective. Emotions are an inherent part of ethical decision-making and one source of information actively stored in case-based knowledge, making them an attribute of cases that likely facilitates case-based learning. Emotions also make cases more realistic, an essential component for effective case-based instruction. The purpose of this study was to investigate the influence of emotional case content, and complementary socio-relational case content, on case-based knowledge acquisition and transfer on future ethical decision-making tasks. Study findings suggest that emotional case content stimulates retention of cases and facilitates transfer of ethical decision-making principles demonstrated in cases. PMID- 22038063 TI - The ethical dilemma of embryonic stem cell research. AB - To determine the knowledge, attitude, and ethical concerns of medical students and graduates with regard to Embryonic Stem Cell (ESC) research. This questionnaire based descriptive study was conducted at the Civil Hospital Karachi (CHK), Pakistan from February to July 2008. A well structured questionnaire was administered to medical students and graduate doctors, which included their demographic profile as well as questions in line with the study objective. Informed consent was taken and full confidentiality was assured to the participants. Data were entered in a Statistical Package for Social Sciences (SPSS version.12) and analyzed. A total of 204 male and 216 female medical students and doctors were administered questionnaires out of which 105 males (51.4%) and 108 females (50%) were aware of the embryonic stem cell research and its ethical implications. Forty percent males and 47% of females were of the opinion that life begins at conception. Forty-six percent males and 39% females were in favor of stem cell research while only 31% males and 28% females supported the ESC research. Less than 1/3 of students supported using frozen embryos for research purposes while more than 2/3 indicated that they were unlikely to support abortion for stem cell research purposes. The majority of the students were in favor of stem cell research with some reservations regarding ESC research. A sizeable number of students withheld their views, reflecting their poor understanding of medical ethics. The result of the study indicates a need for incorporating bioethics into the medical curriculum. PMID- 22038064 TI - The role of PAI-1 and adiponectin on the inflammatory state and energy balance in obese adolescents with metabolic syndrome. AB - Obesity is a chronic inflammatory disease and is considered a risk factor for metabolic syndrome. In this study, 57 obese adolescents with and without metabolic syndrome underwent 1 year of weight loss therapy. At baseline, the metabolic syndrome (MS) patients presented higher values of PAI-1 than the non metabolic syndrome patients (n-MS). After therapy, significant improvements in anthropometrics and biochemical, inflammatory, and neuroendocrine variables were observed in both groups. However, the n-MS group presented better results than the MS group. Indeed, we found positive correlations in both groups between PAI-1 and neuropeptide Y (NPY) and between PAI-1 and NPY/AgRP. Inflammatory biomarkers may thus play a role in energy balance. The clinical trial registration number is NCT01358773. PMID- 22038065 TI - Chlorophyll revisited: anti-inflammatory activities of chlorophyll a and inhibition of expression of TNF-alpha gene by the same. AB - In view of the folklore use of green leaves to treat inflammation, the anti inflammatory property of chlorophylls and their degradation products were studied. Chlorophyll a and pheophytin a (magnesium-free chlorophyll a) from fresh leaves showed potent anti-inflammatory activity against carrageenan-induced paw edema in mice and formalin-induced paw edema in rats. Chlorophyll a inhibited bacterial lipopolysaccharide-induced TNF-alpha (a pro-inflammatory cytokine) gene expression in HEK293 cells, but it did not influence the expression of inducible nitric acid synthase and cyclooxygenase-2 genes. Chlorophyll b only marginally inhibited both inflammation and TNF-alpha gene expression. But both chlorophyll a and chlorophyll b showed the same level of marginal inhibition on 12-O tetradecanoyl-phorbol-13-acetate-induced NF-kappaB activation. Chlorophylls and pheophytins showed in vitro anti-oxidant activity. The study shows that chlorophyll a and its degradation products are valuable and abundantly available anti-inflammatory agents and promising for the development of phytomedicine or conventional medicine to treat inflammation and related diseases. PMID- 22038066 TI - Circadian variation of cell proliferation in HTR-8/SVneo cell line. AB - Circadian clock controls several physiological processes such as cell proliferation. Extravillous trophoblast proliferation is a tightly regulated function playing a fundamental role in maternal vessel remodeling. We recently demonstrated that clock genes Per2 and Dec1 as well as the clock-controlled genes Dbp and Vegf are rhythmically expressed in human extravillous trophoblast-derived HTR-8/SVneo cells. Analyzing the time course of HTR-8/SVneo cell proliferation, a circadian variation in cell number was found. Moreover, we showed a rhythmic expression of mRNAs for Wee1 and stathmin, two genes involved in cell cycle progression. We suggest that circadian clockwork may orchestrate the functionality of the several factors involved in the control of human trophoblast functions that are fundamental for a successfully pregnancy outcome. PMID- 22038068 TI - Glomerular hemophagocytic macrophages in a patient with proteinuria and clinical and laboratory features of hemophagocytic lymphohistiocytosis (HLH). AB - Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous disorder characterized by excessive activation and proliferation of nonmalignant histiocytes, which are commonly found in bone marrow, lymph nodes, spleen and liver in affected patients. Here, we report the presence of glomerular macrophages, including one showing erythrophagocytosis, on renal biopsy in a 25 year-old patient with clinical presentation and laboratory changes consistent with HLH. The clinical course was marked by persistent fever for 2 months, pleural and pericardial effusion, splenomegaly, lymphadenopathy, pancytopenia, cardiac arrhythmias, multiple organ dysfunction, and proteinuria, with demise after a 2-month hospitalization. Positive assay for Epstein-Barr virus (EBV), marked hyperferritinemia, hypofibrinogenemia, hypertriglyceridemia, elevated anti nuclear antibody, proteinuria, and decreased circulating NK cells by flow cytometry were compatible with the diagnosis of HLH. We suggest that the glomerular hemophagocytic macrophages, which have not heretofore been described in the kidney of a patient with HLH, may have contributed to renal dysfunction manifest as proteinuria. PMID- 22038067 TI - BnRCH gene inhibits cell growth of Hela cells through increasing the G2 phase of cell cycle. AB - The ubiquitin-proteasome pathway (UPP) is an important protein degradation system universally existing in eukaryotic organisms from yeast to human. In this system, hundreds of E3 ubiquitin-protein ligases are most important because they provide the substrate specificity and control many cellular processes. UPP has been found to be relevant to cancer development. BnRCH, the protein product from a novel gene isolated from Brassica napus, also has E3 ubiquitin-protein ligase activity. In order to exploit its potential use, human cervical carcinoma cell Hela (Hela cells) was transiently and stably transfected with BnRCH. The experimental results demonstrated: (1) in Hela cells, BnRCH inhibited the cell growth of Hela cells and increased their sensitivity to the anti-cancer chemotherapeutic drug cisplatin; and (2) the growth inhibition effect of BnRCH in Hela cells was found due to G2 phase cell cycle arrest with the transcriptional up-regulation of p21 (waf1/cip1), rather than apoptosis. This research suggests BnRCH has potential use in cancer therapy. PMID- 22038069 TI - Entrapment of Lactobacillus acidophilus into alginate beads for the effective treatment of cold restraint stress induced gastric ulcer. AB - Lactobacillus acidophilus (LAB) loaded alginate floating beads (FBs) were developed with an intent to (i) preserve their viability during manufacture and upon exposure to adverse physiological conditions existing in the stomach, (ii) achieve an increased stay of the system in the stomach for improved pharmacodynamics and to provide for their effective establishment within the gastric mucosa. In vitro characterization of developed beads was performed in terms of entrapment efficiency, buoyancy, and surface as well as cross sectional morphology and viability studies of LAB in a gastric environment. The developed system was evaluated and was found to be significantly better in an experimental model of cold restraint stress (CRS) induced gastric ulcer model in terms of ulcer index, hemorrhagic streak length, histopathological and biochemical markers and their cross talk with reactive oxygen/nitrogen species. The present study emphasizes the advantages and future potential of probiotic loaded FBs in gastric disorders. PMID- 22038070 TI - Cervical cancer screening among immigrant Hispanics: an analysis by country of origin. AB - As the largest and most diverse ethnic minority population in the U.S., it is important to examine differences in and correlates of Pap test adherence among Hispanics by country of origin. The data for these analyses are baseline responses from a Randomized Controlled Trial. Bivariate and multivariable logistic regression models were conducted among Hispanic immigrant women who identified as Mexican, Puerto Rican, Dominican, or Central/South American (n = 1,305). There were significant differences in Pap test adherence: Dominicans (81.6%), Mexicans (77.5%), Central/South Americans (71.2%), and Puerto Ricans (69.3%). In multivariable analyses, there were different correlates of Pap test adherence for each country of origin. For example, marriage status (P = .0001) and younger age (P = .006) were positively associated with adherence among Mexican women. This research provides insight into the variability that exists among Hispanics and can help improve understanding of important determinants that may influence Pap test screening among diverse Hispanics. PMID- 22038071 TI - Risk factors associated with hepatitis C virus infection in an urban population of the State of Mexico. AB - The aim of this study was to determine the seroprevalence anti-hepatitis C virus (HCV) antibodies and risk factors associated with patients attending primary-care clinics in the State of Mexico. A cross-sectional, prospective study was conducted on 10,524 consenting patients with history of at least one risk factor for HCV. Antibodies were detected by immunoassay, third-generation ELISA; RT-PCR was carried out to confirm HCV infection. The seroprevalence of HCV antibodies was 1.2% (128). The most common risk factor was blood transfusion prior to 1993 (56.3%), followed by family history of cirrhosis 29 (22.7%); tattoos and/or piercings, 28 (21.9%); high-risk sexual practices, 4 (3.1%); healthcare work, 8 (6.3%); and intravenous drug use, 1 (8%). RT-PCR was performed on samples from 83 patients. Forty-five were considered positive. Genotype 1a was the most prevalent (37.7%). PMID- 22038072 TI - A new satellite RNA is associated with natural infections of cucumber mosaic virus in succulent snap bean. AB - Cucumber mosaic virus (CMV) was consistently recovered from symptomatic snap bean plants during surveys conducted in 2007 and 2008 in central Wisconsin. A large proportion of these CMV-infected plants contained a single-stranded linear RNA molecule consisting of 339 nucleotides and sharing 90-94% sequence identity with other satellite (sat) RNAs of CMV. Comparison of this satRNA sequence with currently available CMV satRNA sequences suggests this to be a novel satRNA. PMID- 22038073 TI - Genomic sequence of infectious hypodermal and hematopoietic necrosis virus (IHHNV) KLV-2010-01 originating from the first Korean outbreak in cultured Litopenaeus vannamei. AB - Due to the need to track and monitor genetic diversity, the genome of the infectious hypodermal and hematopoietic necrosis virus (IHHNV) strain KLV-2010-01 in cultured Litopenaeus vannamei shrimp that originated from the first Korean outbreak in 2010 was sequenced and analyzed. The genome, with a length of 3914 nucleotides, was sequenced from the Korean IHHNV. The genome encoded three large and overlapping open reading frames: ORF1 (NS-1) of 2001 bp, ORF2 (NS-2) of 1092 bp and ORF3 (capsid protein) of 990 bp. The overall organization, size and predicted amino acid sequence of the three ORFs in Korean IHHNV were highly similar to those of members of the infectious IHHNV group, and the most closely related strains were IHHNVs described from Ecuador and Hawaii. Additionally, phylogenetic analysis showed that the Korean IHHNV was clustered with lineage III in the infectious IHHNV group and was most similar to IHHNV isolates from Ecuador, China and Taiwan. PMID- 22038074 TI - Differentiation of infectious bursal disease virus (IBDV) genome segment B of very virulent and classical lineage by RT-PCR amplification and restriction enzyme analysis. AB - Molecular characterization of IBDV usually relies on the analysis of segment A of the bi-segmented, double-stranded RNA genome. Although segments B of classical and very virulent IBDVs differ significantly, re-assortment of genome segments does occur, and molecular epidemiological studies demand the analysis of both segments. An RT-PCR and restriction enzyme analysis for molecular discrimination between genome segment B of classical and very virulent IBDVs is described. Tested on eight IBDV strains/isolates, the protocol successfully identified very virulent and classical IBDVs as well as a segment reassortant. This approach is a valuable tool for molecular epidemiological studies on IBDV. PMID- 22038075 TI - Synthesis of chiral hybrid nanotubes of magnetite nanoparticles and conducting polymers. AB - New chiral magnetite nanoparticles with a polymerizable group produced polymer composite films on an electrode surface and the hybrid nanotubes of magnetite nanoparticles and polythiophene from their template-based electropolymerization. PMID- 22038076 TI - Conformation specificity and arene binding in a peptide composed only of Lys, Ile, Ala and Gly. AB - The first life on Earth is believed to have been based on RNA, but might have taken advantage of amino acids and short peptides which form readily under conditions like those of the primitive Earth. We have shown that simple peptides adopt specifically folded four-helix bundle structures that can recognize and cleave RNA. Here, to explore the limits of conformational specificity, we characterize a simpler peptide composed of just Lys, Ile, Ala, and Gly called KIA7I. Using nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations, we find kinks in the helices of KIA7I and multiple C-terminal conformations. These results suggest that the C-terminal Ile residue does not completely occupy the hydrophobic pocket that is filled by aromatic side-chains in well-folded KIA7 variants. The capacity of arenes to fill this cavity was tested. Using NMR, we show that benzene and phenol can bind KIA7I, but do not bind the well-folded variant KIA7W or hen egg white lysozyme. Benzene also binds Abeta(1-40), a mostly disordered polypeptide implicated in Alzheimer's disease. 8 Anilinonaphthalene-1-sulfonate (ANS) fluorescence is further enhanced in the presence of both KIA7I and arenes relative to KIA7I alone. This ANS fluorescence enhancement is stronger for smaller and less polar arenes and less ordered KIA variants. These results suggest that arenes are not confined to the pocket, but penetrate and loosen the hydrophobic core of KIA7I. PMID- 22038077 TI - Depth-sensing analysis of cytoskeleton organization based on AFM data. AB - Atomic force microscopy is a common technique used to determine the elastic properties of living cells. It furnishes the relative Young's modulus, which is typically determined for indentation depths within the range 300-500 nm. Here, we present the results of depth-sensing analysis of the mechanical properties of living fibroblasts measured under physiological conditions. Distributions of the Young's moduli were obtained for all studied cells and for every cell. The results show that for small indentation depths, histograms of the relative values of the Young's modulus described the regions rich in the network of actin filaments. For large indentation depths, the overall stiffness of a whole cell was obtained, which was accompanied by a decrease of the modulus value. In conclusion, the results enable us to describe the non-homogeneity of the cell cytoskeleton, particularly, its contribution linked to actin filaments located beneath the cell membrane. Preliminary results showing a potential application to improve the detection of cancerous cells, have been presented for melanoma cell lines. PMID- 22038078 TI - Age cohort differences in the effects of gay-related stigma, anxiety and identification with the gay community on sexual risk and substance use. AB - Different cohorts of gay/bisexual men experience unique developmental factors given their distinct socio-historical contexts. This study examined the moderating effects of age on three psychosocial predictors of HIV risk behavior and substance use. Analyses drew on data from a study of substance using HIV negative and unknown status gay/bisexual men (N= 302) at risk for HIV infection. Anxiety was a strong independent predictor of sexual risk and substance use, and its effects on the sex risk outcomes were moderated by age, such that older and more anxious participants had more frequent instances of sexual risk. Identification with the gay community protected against HIV risk, and its effects on sex risk outcomes were moderated by age, such that younger participants who identified with the gay community reported less sexual risk. Understanding HIV risk within socio-historical contexts is essential in tailoring prevention by taking into account recipients' ages. PMID- 22038079 TI - Efficacy of an intervention for families living with HIV in Thailand: a randomized controlled trial. AB - This study evaluates the efficacy of an intervention for persons living with HIV (PLH) and their family members in Thailand. A randomized controlled trial of 813 PLH and family members was carried out at four district hospitals in Thailand. Participants completed Computer Assisted Personal Interview assessments at baseline, 6, 12, 18, and 24 months. The primary outcome was quality of life (QoL); other measures included depressive symptoms and family functioning. Relative to the standard care condition, the intervention group reported significantly improved QoL at 6 months (P = 0.0014). When the intervention efficacy was stratified by baseline depressive symptoms (low vs. high), intervention efficacy was observed only among those with low depressive symptoms. Study findings suggest that the intervention was more efficacious for participants with less depressive symptoms and better family functioning. Extensive interventions may be optimal for those who have the capacity to learn the tools and skills. PMID- 22038080 TI - Risk for Heterosexual HIV Transmission Among Non-Injecting Female Partners of Injection Drug Users in Estonia. AB - The HIV epidemic in Estonia, as with other eastern European countries, is currently concentrated among injection drug users (IDUs). Non-IDUs who have IDU sex partners could serve as a potential bridge in an expanding epidemic. We applied HIV transmission modelling to data collected from non-IDU/IDU heterosexual couples in Kohtla-Jarve, Estonia to estimate HIV risk from IDUs to their sex partners based on self-reported sexual behaviors shared by the couple. IDUs and their current main non-injecting sex partners were recruited for an interviewer-administered survey and HIV testing. Bernoulli modelling techniques were applied to estimate the risk of HIV transmission (incidence) among HIV negative non-injecting female partners of male IDUs. The estimated HIV incidence in this population of non-injecting women with only main sexual partners in the last 6 months ranged from 3.24 to 4.94 HIV seroconversions per 100 person years depending on the value used in the models for the per act transmission rate during acute stage infection. Non-IDUs who have IDU sex partners are at high risk for HIV and could serve as a potential bridge to a more generalized epidemic. Whether this might lead to an expansion of the HIV epidemic beyond core groups in Estonia or other Eastern European countries warrants closer study. PMID- 22038081 TI - Correlates of staying safe behaviors among long-term injection drug users: psychometric evaluation of the staying safe questionnaire. AB - We report on psychometric properties of a new questionnaire to study long-term strategies, practices and tactics that may help injection drug users (IDUs) avoid infection with HIV and hepatitis C. Sixty-two long-term IDUs were interviewed in New York City in 2009. Five scales based on a total of 47 items were formed covering the following domains: stigma avoidance, withdrawal prevention, homeless safety, embedding safety within a network of users, and access to resources/social support. All scales (alpha >= .79) except one (alpha = .61) were highly internally consistent. Seven single-item measures related to drug use reduction and injection practices were also analyzed. All variables were classified as either belonging to a group of symbiotic processes that are not directly focused upon disease prevention but nonetheless lead to risk reduction indirectly or as variables describing prevention tactics in risky situations. Symbiotic processes can be conceived of as unintentional facilitators of safe behaviors. Associations among variables offer suggestions for potential interventions. These Staying Safe variables can be used as predictors of risk behaviors and/or biological outcomes. PMID- 22038082 TI - Parole officer-parolee relationships and HIV risk behaviors during community supervision. AB - We tested if good parole officer (PO)-parolee relationships reduce HIV risk behaviors during parole, as they do for risk of rearrest. Analyses used data from 374 parolees enrolled in a randomized clinical trial. Past month HIV risk behaviors were assessed by interview at baseline, 3- and 9-months after parole initiation. The Working Alliance Inventory and the Dual-Role Relationships Inventory measured PO relationship. Gender-stratified multivariate regressions tested associations of PO-parolee relationship with sex with multiple partners, unprotected sex with risky partner(s), and drug injection. Women parolees (n = 65) who reported better PO relationship characteristics were less likely to report having multiple sex partners [adjusted odds ratio: 0.82 (0.69, 0.98) at 3 months, 0.89 (0.80, 0.99) at 9-months], and, among those reporting multiple sex partners, had fewer partners on average [adjusted relative risk 0.98 (0.96, 0.99)]. These effects were not found among men. PO-parolee relationship quality can influence sexual risk behaviors among women parolees. PMID- 22038083 TI - Mathematical studies on the sterile insect technique for the Chikungunya disease and Aedes albopictus. AB - Chikungunya is an arthropod-borne disease caused by the Asian tiger mosquito, Aedes albopictus. It can be an important burden to public health and a great cause of morbidity and, sometimes, mortality. Understanding if and when disease control measures should be taken is key to curtail its spread. Dumont and Chiroleu (Math Biosc Eng 7(2):315-348, 2010) showed that the use of chemical control tools such as adulticide and larvicide, and mechanical control, which consists of reducing the breeding sites, would have been useful to control the explosive 2006 epidemic in Reunion Island. Despite this, chemical control tools cannot be of long-time use, because they can induce mosquito resistance, and are detrimental to the biodiversity. It is therefore necessary to develop and test new control tools that are more sustainable, with the same efficacy (if possible). Mathematical models of sterile insect technique (SIT) to prevent, reduce, eliminate or stop an epidemic of Chikungunya are formulated and analysed. In particular, we propose a new model that considers pulsed periodic releases, which leads to a hybrid dynamical system. This pulsed SIT model is coupled with the human population at different epidemiological states in order to assess its efficacy. Numerical simulations for the pulsed SIT, using an appropriate numerical scheme are provided. Analytical and numerical results indicate that pulsed SIT with small and frequent releases can be an alternative to chemical control tools, but only if it is used or applied early after the beginning of the epidemic or as a preventive tool. PMID- 22038084 TI - Global dynamics of a reaction and diffusion model for Lyme disease. AB - This paper is devoted to the mathematical analysis of a reaction and diffusion model for Lyme disease. In the case of a bounded spatial habitat, we obtain the global stability of either disease-free or endemic steady state in terms of the basic reproduction number R0. In the case of an unbounded spatial habitat, we establish the existence of the spreading speed of the disease and its coincidence with the minimal wave speed for traveling fronts. Our analytic results show that R0 is a threshold value for the global dynamics and that the spreading speed is linearly determinate. PMID- 22038085 TI - Longitudinal evidence for the association between work-related physical exposures and neck and/or shoulder complaints: a systematic review. AB - BACKGROUND: Most existing reviews focus on evidence for the association between neck and/or shoulder complaints and physical exposures at the workplace gathered from cross-sectional studies. In comparison, this review summarizes existing evidence from longitudinal studies only. METHODS: A systematic literature research was conducted in Medline and EMBASE (1975-2009), and all studies were scanned by at least two researchers according to strict inclusion criteria. Levels of evidence were assigned according to the number of studies reporting similar findings, and according to the methodological quality of the included studies. RESULTS: Altogether 21 longitudinal studies (19 high-quality studies) met the inclusion criteria and were included in this review. In comparison with former reviews, we found strong evidence for an association between shoulder complaints and manual material handling (MMH) (range between Odds Ratio (OR) 1.4 and 4.9), vibration (range between OR 1.6 and OR 2.5), trunk flexion or rotation (range between OR 1.8 and OR 5.1), and working with hands above shoulder level (range between OR 1.1 and OR 1.8). Apart from that, the included studies confirmed existing knowledge on the association between physical exposures at the workplace and neck and/or shoulder complaints. CONCLUSIONS: This analysis of longitudinal studies allowed for new evidence with regard to four cause-effect chains between physical exposures at work and the development of shoulder, neck and neck/shoulder complaints. As outcome variables varied greatly among the included studies, harmonization in studies on musculoskeletal research is desirable. PMID- 22038086 TI - Burnout and effort-reward imbalance improvement for teachers by a manual-based group program. AB - OBJECTIVE: We developed a manual-based psychological group program aimed at teachers and focussing on their professional relationships. The intervention comprised ten sessions over a 10-month period. The aim of the program was to strengthen teachers' health. We investigated whether the effects of our intervention, during which the MBI and ERI were applied, result in general alleviation of occupational stress experienced by teachers. METHODS: This is a randomized controlled trial. All teachers (N = 2,484) of two school types (grammar schools and secondary modern schools) in 3 districts of southwestern Germany were invited to take part in our program. All teachers declaring their interest (N = 337) in the intervention were included in the project. They were randomly assigned to either the intervention group (N = 171) or to the control group (N = 166). RESULTS: We found that teachers who participated in at least 50% of the program benefited from this short intervention. Significant improvement was achieved on the two MBI scales, Emotional Exhaustion and Personal Accomplishment, as well as on the ERI subscale Appreciation. CONCLUSION: Teachers' occupational stress level may be decreased by taking part in a short manual-based psychological group intervention that focuses on more effective handling of interpersonal problems in school. Therefore, teachers should receive support and guidance in developing the appropriate skills necessary to cope with stress appropriately. PMID- 22038087 TI - Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to polycyclic aromatic hydrocarbons with a generic, cross-chemical predictive PBTK-model. AB - INTRODUCTION: A physiologically based toxicokinetic (PBTK) model can predict blood and urine concentrations, given a certain exposure scenario of inhalation, dermal and/or oral exposure. The recently developed PBTK-model IndusChemFate is a unified model that mimics the uptake, distribution, metabolism and elimination of a chemical in a reference human of 70 kg. Prediction of the uptake by inhalation is governed by pulmonary exchange to blood. Oral uptake is simulated as a bolus dose that is taken up at a first-order rate. Dermal uptake is estimated by the use of a novel dermal physiologically based module that considers dermal deposition rate and duration of deposition. Moreover, evaporation during skin contact is fully accounted for and related to the volatility of the substance. Partitioning of the chemical and metabolite(s) over blood and tissues is estimated by a Quantitative Structure-Property Relationship (QSPR) algorithm. The aim of this study was to test the generic PBTK-model by comparing measured urinary levels of 1-hydroxypyrene in various inhalation and dermal exposure scenarios with the result of model simulations. EXPERIMENTAL: In the last three decades, numerous biomonitoring studies of PAH-exposed humans were published that used the bioindicator 1-hydroxypyrene (1-OH-pyrene) in urine. Longitudinal studies that encompass both dosimetry and biomonitoring with repeated sampling in time were selected to test the accuracy of the PBTK-model by comparing the reported concentrations of 1-OHP in urine with the model-predicted values. Two controlled human volunteer studies and three field studies of workers exposed to polycyclic aromatic hydrocarbons (PAH) were included. RESULTS: The urinary pyrene metabolite levels of a controlled human inhalation study, a transdermal uptake study of bitumen fume, efficacy of respirator use in electrode paste workers, cokery workers in shale oil industry and a longitudinal study of five coke liquefaction workers were compared to the PBTK-predicted values. The simulations showed that the model-predicted concentrations of urinary pyrene and metabolites over time, as well as peak-concentrations and total excreted amount in different exposure scenarios of inhalation and transdermal exposure were in all comparisons within an order of magnitude. The model predicts that only a very small fraction is excreted in urine as parent pyrene and as free 1-OH-pyrene. The predominant urinary metabolite is 1-OH-pyrene-glucuronide. Enterohepatic circulation of 1-OH pyrene-glucuronide seems the reason of the delayed release from the body. CONCLUSIONS: It appeared that urinary excretion of pyrene and pyrene-metabolites in humans is predictable with the PBTK-model. The model outcomes have a satisfying accuracy for early testing, in so-called 1st tier simulations and in range finding. This newly developed generic PBTK-model IndusChemFate is a tool that can be used to do early explorations of the significance of uptake of pyrene in the human body following industrial or environmental exposure scenarios. And it can be used to optimize the sampling time and urine sampling frequency of a biomonitoring program. PMID- 22038088 TI - Working conditions of female part-time and full-time teachers in relation to health status. AB - PURPOSE: Teacher's volume of employment and health status are controversially discussed in the current literature. This study focused on female teachers with part-time versus full-time jobs in association with working conditions and health status depending on age. METHOD: A sample of 263 part-time and 367 full-time female teachers (average age 46.7 +/- 7.8 vs. 46.0 +/- 6.3) participated in an occupational health screening. Specific work conditions, stressors (job history questionnaire) and effort-reward-imbalance ratio (ERI-Q) were measured and their relationships to mental and physical health were analysed. Health status was quantified by complaints (BFB questionnaire), general mental health status (GHQ 12) and cardiovascular risk factors. RESULTS: On average, teachers in part-time positions reported 36 and in full-time positions 42 h per week. The effort-reward ratios were significantly associated with the volume of employment. Teachers in part-time jobs had only a slightly lower ERI-ratio. There were no differences between full-time and part-time teachers regarding health status. Eighteen percentage of both groups reported impaired mental health (GHQ >= 5), 48% of part time teachers and 53% of full-time teachers suffered from high blood pressure. Low physical fitness was observed in 12% of part-time and 6% of full-time teachers. In this study, neither the volume of employment nor working conditions were found to be significantly correlated with health status. CONCLUSION: Part time and full-time employment status did not appear to influence health in the teaching profession. Although there are differences in quantitative working demands, while the health status does not differ between both teacher groups. PMID- 22038089 TI - Neuromotor function in ship welders after cessation of manganese exposure. AB - PURPOSE: The aim of the present study was to investigate whether previous long term exposure to manganese (Mn) via inhalation of welding fumes can cause persistent impairment in neuromotor function even long after cessation of exposure. METHODS: Quantitative tests of tremor, motor speed, manual dexterity, diadochokinesis, eye-hand coordination and postural stability were administered to 17 retired ship welders (mean age 69 years), with mean exposure time 28 years. The welders' exposure had ceased on average 18 years before the study. A cumulative exposure index (CEI) was calculated for each of the former welders. The welders were compared with 21 referents from the same shipyards (mean age was 66 years). RESULTS: Former welders performed less well than referents in the grooved pegboard test, and poorer performance was associated with CEI. The performance in most of the other neurobehavioral tests was similar between groups, but the welders tended to perform slightly better than the referents in tests demanding hand steadiness. The latter finding may be due to a training effect from their former working tasks or selection bias into or out of this occupation. CONCLUSIONS: In the present study of welders with previous welding fume exposure, former welders and referents performed similarly in most of the neurobehavioral tests. Previous adverse effects on the neuromotor system might have ceased, and decreased neuromotor function due to normal aging processes in both groups might have disguised any slight effect of previous Mn exposure. The poorer performance in the grooved pegboard test among welders may indicate an adverse effect on motor function of long-term exposure to Mn, but this finding has to be confirmed by other studies. PMID- 22038090 TI - The relative contribution of work exposure, leisure time exposure, and individual characteristics in the onset of arm-wrist-hand and neck-shoulder symptoms among office workers. AB - PURPOSE: To identify the risk factors for the onset of arm-wrist-hand and neck shoulder symptoms among office workers and to estimate the relative contribution of these risk factors by calculating Population Attributable Fractions (PAFs). METHODS: A prospective cohort study was conducted among 1951 office workers with a follow-up duration of 2 years. Data on self-reported risk factors were collected at baseline and after 1 year of follow-up. Every 3 months, the occurrence of upper extremity symptoms was assessed using questionnaires. PAFs for individual risk factors were estimated based on Rate ratios (RRs) obtained from Poisson regression using Generalized Estimation Equations. RESULTS: Previous disabling symptoms were identified as the most important risk factor for the onset of arm-wrist-hand and neck-shoulder symptoms. Modifiable risk factors for arm-wrist-hand symptoms with relatively large PAFs were: at least 4 h per day of self-reported computer use at work, high level of overcommitment, and low task variation and for neck-shoulder symptoms: supporting the arms during keyboard use and at least 4 h per day of self-reported mouse use at work. Compared to having 0 or 1 risk factor, the RR for arm-wrist-hand symptoms increased to 6.2 (95% CI 3.7 10.5) for having 5-7 potentially modifiable risk factors and for neck-shoulder symptoms to 3.0 (95% CI 2.1-4.4) for having 4 or 5 potentially modifiable risk factors. CONCLUSION: Preventive interventions at the population level should be aimed at changing modifiable risk factors with large PAFs. At the individual level, preventive interventions should be aimed at changing multiple modifiable risk factors simultaneously. PMID- 22038091 TI - Characterization of an inositol 1,3,4-trisphosphate 5/6-kinase gene that is essential for drought and salt stress responses in rice. AB - Drought and salt stresses are major limiting factors for crop production. To identify critical genes for stress resistance in rice (Oryza sativa L.), we screened T-DNA mutants and identified a drought- and salt-hypersensitive mutant dsm3. The mutant phenotype was caused by a T-DNA insertion in a gene encoding a putative inositol 1,3,4-trisphosphate 5/6-kinase previously named OsITPK2 with unknown function. Under drought stress conditions, the mutant had significantly less accumulation of osmolytes such as proline and soluble sugar and showed significantly reduced root volume, spikelet fertility, biomass, and grain yield; however, malondialdehyde level was increased in the mutant. Interestingly, overexpression of DSM3 (OsITPK2) in rice resulted in drought- and salt hypersensitive phenotypes and physiological changes similar to those in the mutant. Inositol trisphosphate (IP3) level was decreased in the overexpressors under normal condition and drought stress. A few genes related to osmotic adjustment and reactive oxygen species scavenging were down-regulated in the mutant and overexpression lines. The expression level of DSM3 promoter-driven beta-glucuronidase (GUS) reporter gene in rice was induced by drought, salt and abscisic acid. Protoplast transient expression assay indicated that DSM3 is an endoplasmic reticulum protein. Sequence analysis revealed six putative ITPKs in rice. Transcript level analysis of OsITPK genes revealed that they had different tempo-spatial expression patterns, and the responses of DSM3 to abiotic stresses, including drought, salinity, cold, and high temperature, were distinct from the other five members in rice. These results together suggest that DSM3/OsITPK2 is an important member of the OsITPK family for stress responses, and an optimal expression level is essential for drought and salt tolerance in rice. PMID- 22038092 TI - Analysis of raphidophyte assimilatory nitrate reductase reveals unique domain architecture incorporating a 2/2 hemoglobin. AB - Eukaryotic assimilatory nitrate reductase (NR) is a multi-domain protein that catalyzes the rate-limiting step in nitrate assimilation. This protein is highly conserved and has been extensively characterized in plants and algae. Here, we report hybrid NRs (NR2-2/2HbN) identified in two microalgal species, Heterosigma akashiwo and Chattonella subsalsa, with a 2/2 hemoglobin (2/2Hb) inserted into the hinge 2 region of a prototypical NR. 2/2Hbs are a class of single-domain heme proteins found in bacteria, ciliates, algae and plants. Sequence analysis indicates that the C-terminal FAD/NADH reductase domain of NR2-2/2HbN retains identity with eukaryotic NR, suggesting that the 2/2Hb domain was inserted interior to the existing NR domain architecture. Phylogenetic analysis supports the placement of the 2/2Hb domain of NR2-2/2HbN within group I (N-type) 2/2Hbs with high similarity to mycobacterial 2/2HbNs, known to convert nitric oxide to nitrate. Experimental data confirms that H. akashiwo is capable of metabolizing nitric oxide and shows that HaNR2-2/2HbN expression increases in response to nitric oxide addition. Here, we propose a mechanism for the dual function of NR2 2/2HbN in which nitrate reduction and nitric oxide dioxygenase reactions are cooperative, such that conversion of nitric oxide to nitrate is followed by reduction of nitrate for assimilation as cellular nitrogen. PMID- 22038093 TI - Plant MCM proteins: role in DNA replication and beyond. AB - Mini-chromosome maintenance (MCM) proteins form heterohexameric complex (MCM2-7) to serve as licensing factor for DNA replication to make sure that genomic DNA is replicated completely and accurately once during S phase in a single cell cycle. MCMs were initially identified in yeast for their role in plasmid replication or cell cycle progression. Each of six MCM contains highly conserved sequence called "MCM box", which contains two ATPase consensus Walker A and Walker B motifs. Studies on MCM proteins showed that (a) the replication origins are licensed by stable binding of MCM2-7 to form pre-RC (pre-replicative complex) during G1 phase of the cell cycle, (b) the activation of MCM proteins by CDKs (cyclin-dependent kinases) and DDKs (Dbf4-dependent kinases) and their helicase activity are important for pre-RC to initiate the DNA replication, and (c) the release of MCMs from chromatin renders the origins "unlicensed". DNA replication licensing in plant is, in general, less characterized. The MCMs have been reported from Arabidopsis, maize, tobacco, pea and rice, where they are found to be highly expressed in dividing tissues such as shoot apex and root tips, localized in nucleus and cytosol and play important role in DNA replication, megagametophyte and embryo development. The identification of six MCM coding genes from pea and Arabidopsis suggest six distinct classes of MCM protein in higher plant, and the conserved function right across the eukaryotes. This overview of MCMs contains an emphasis on MCMs from plants and the novel role of MCM6 in abiotic stress tolerance. PMID- 22038094 TI - Wood identification with PCR targeting noncoding chloroplast DNA. AB - Wood identification is extremely important in the modern forest industry. It also has significant applications in forensics, as well as in archeology and ecological research. In this study, five universal primer pairs amplifying chloroplast noncoding sequences of 300-1,200 bp were designed. Sequencing these amplicons in combination can lead to reliable identification of logs and wood products to cultivar, ecotype, or even the falling population. These primer pairs work on both gymnosperms and angiosperm trees. They also are potentially applicable to accurately identify shrubs and herbaceous species. In addition, a wood DNA purification method is proposed in which N-phenacylthiazolium bromide (PTB) is used to increase the quality and quantity of extracted DNA. This method was first validated using air-dried timber disks from three different tree species that were felled 4 years ago. The sapwood and outer heartwood provided the best locations for DNA extraction. The method was also successfully applied to extract DNA from the recalcitrant processed white oak wood, randomly selected staves of wine barrels. The single nucleotide polymorphism detected on the oak DNA sequences showed correlation to their geographical origins. PMID- 22038095 TI - Colistin A and colistin B among inhibitory substances of Paenibacillus polymyxa JB05-01-1. AB - Recently, we isolated and reported the antagonism of Paenibacillus polymyxa JB05 01-1 (P. polymyxa JB05-01-1) against Gram-negative bacteria. Here, we provide more insights and attribute the abovementioned antagonism to the production of colistins A and B, which were purified by Amberlite column exchange, C18 column hydrophobicity, superdex 75 16/60 gel filtration chromatography connected to fast protein liquid chromatography and identified by MALDI TOF/TOF, and manual nanospray analysis. The amount of colistin A and colistin B recovered from 500 ml of culture supernatant was about 0.05 mg. The specific activity and the average recovery of the eluted substances were 5,120 AU/mg and 1.1%, respectively. The minimal inhibitory concentrations of the purified colistins against Escherichia coli O157:H7 and Pseudomonas fluorescens LRC R73 were 0.13 and 0.62 MUg/ml, respectively. PMID- 22038096 TI - Simvastatin suppresses apoptosis in vulnerable atherosclerotic plaques through regulating the expression of p(53), Bcl-2 and Bcl-xL. AB - PURPOSE: Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has antioxidant and anti-inflammatory properties that are independent of lipid-lowering abilities. This experiment was carried out to explore the effects of simvastatin on apoptosis in vulnerable atherosclerotic plaques of apoE deficient mice. METHODS AND RESULTS: Eight weeks-old apoE(-/-) mice were fed a Western-type diet. Vulnerable atherosclerotic lesions were formed in the branchiocephalic artery at the age of 30-weeks, before simvastatin administration for 8 weeks. Simvastatin did neither affect the levels of plasma glucose and lipids, nor the size of atherosclerotic lesions. Analysis of plaque composition showed that simvastatin decreased the area of lipid core and increased the amounts of macrophages and smooth muscle cells in atherosclerotic plaques of apoE(-/-) mice. In addition, simvastatin down-regulated the expression of vascular cell adhesion molecule-1 (VCAM-1) by both inhibition of nuclear factor kappa B (NF-kB) activation and suppression of the expression of the receptor for advanced glycation end products (RAGE). Moreover, we found that simvastatin administration led to reduced TUNEL-positive cells in the aortic root lesions, accompanied by up-regulation of Bcl-2 and Bcl-xL expression, and decreased P(53) expression as shown by Western blot. CONCLUSION: In the present study, we show novel data to suggest that simvastatin could suppress apoptosis in vulnerable atherosclerotic plaques of apoE(-/-) mice by regulating the expression of apoptosis-related proteins, such as p(53), Bcl-2 and Bcl-xL. PMID- 22038098 TI - Efficient hydrogenation of biomass-derived cyclic di-esters to 1,2-diols. AB - The unprecedented homogeneous hydrogenation of cyclic di-esters, in particular biomass-derived glycolide and lactide, to the corresponding 1,2-diols is catalyzed by Ru(II) PNN (1) and Ru(II) CNN (2) pincer complexes under mild hydrogen pressure and (in the case of 1) neutral conditions. No racemization was observed when a chiral di-ester was used. PMID- 22038097 TI - SIRT1 is required for long-term growth of human mesenchymal stem cells. AB - Human mesenchymal stem cells (MSCs) have therapeutic potential because of their ability to self-renew and differentiate into multiple tissues. However, senescence often occurs in MSCs when they are cultured in vitro and the molecular mechanisms underlying this effect remain unclear. In this study, we found that NAD-dependent protein deacetylase SIRT1 is differentially expressed in both human bone marrow-derived MSCs (B-MSCs) and adipose tissue-derived MSCs after increasing passages of cell culture. Using lentiviral shRNA we demonstrated that selective knockdown of SIRT1 in human MSCs at early passage slows down cell growth and accelerates cellular senescence. Conversely, overexpression of SIRT1 delays senescence in B-MSCs that have undergone prolonged in vitro culturing and the cells do not lose adipogenic and osteogenic potential. In addition, we found that the delayed accumulation of the protein p16 is involved in the effect of SIRT1. However, resveratrol, which has been used as an activator of SIRT1 deacetylase activity, only transiently promotes proliferation of B-MSCs. Our findings will help us understand the role of SIRT1 in the aging of normal diploid cells and may contribute to the prevention of human MSCs senescence thus benefiting MSCs-based tissue engineering and therapies. PMID- 22038099 TI - Implementing biosecurity education: approaches, resources and programmes. AB - This paper aims to present possible approaches, resources and programmes to introduce the topic of biosecurity to life scientists and engineers at the higher education level. Firstly, we summarise key findings from a number of international surveys on biosecurity education that have been carried out in the United States, Europe, Israel and the Asia-Pacific region. Secondly, we describe the development of our openly-accessible education resource, illustrating the scope and content of these materials. Thirdly, we report on actual cases of biosecurity education that have been implemented. These include achievements in and lessons derived from the implementation of biosecurity education at the National Defense Medical College in Japan. These experiences are followed by presentation of the expert-level "Train-the-Trainer" programmes subsequently launched by the University of Bradford in the United Kingdom. These examples will help readers to understand how educators can enhance their own understanding about biosecurity issues and how they can then disseminate their knowledge through development of their own customised, relevantly-targeted and stage tailored education programmes within their own life science communities. By providing these examples, we argue that education for life scientists, policy makers and other stakeholders about social responsibility on dual-use issues is easily achievable and need not be expensive, time-consuming or over-burdening. We suggest that recurring classes or courses be held at appropriate times during educational programmes to accommodate the developing expertise and advancing learning stages of students. PMID- 22038100 TI - Delivery by Cesarean section and early childhood respiratory symptoms and disorders: the Norwegian mother and child cohort study. AB - Studies have indicated that children delivered by cesarean section are at an increased risk of developing wheezing and asthma. This could be the result of an altered immune system development due to delayed gut colonization or of increased neonatal respiratory morbidity. The authors examined the associations between delivery by cesarean section and the development of wheezing, asthma, and recurrent lower respiratory tract infections in children up to 36 months of age among 37,171 children in the Norwegian Mother and Child Cohort Study. Generalized linear models were used in the multivariable analysis. Children delivered by cesarean section had an increased likelihood of current asthma at 36 months of age (relative risk = 1.17, 95% confidence interval: 1.03, 1.32), and the association was stronger among children of nonatopic mothers (relative risk = 1.33, 95% confidence interval: 1.12, 1.58). No increased risk of wheezing or recurrent lower respiratory tract infections was seen among children delivered by cesarean section. Findings were similar among children delivered by acute and elective cesarean section. In conclusion, children delivered by cesarean section may have an increased risk of current asthma at 36 months, but residual confounding cannot be excluded. In future prospective studies, investigators should reexamine this association in different age groups. PMID- 22038101 TI - The association between living through a prolonged economic depression and the male:female birth ratio--a longitudinal study from Cuba, 1960-2008. AB - The Trivers-Willard hypothesis suggests that populations respond to scarcity by decreasing the ratio of males to females at livebirth. Cuba experienced an extreme economic depression in the 1990s called the "special period." Using time series analysis, the authors studied the impact of this event on the male:female sex ratio at birth in Cuba from 1960 to 2008. From 1990 to 1993, the per capita gross domestic product in Cuba decreased by 36%. By use of a definition of the special period from 1991 to 1998, there was a prolonged increase in the male:female ratio of livebirths during this period of economic depression (P < 0.001), from 1.06 at baseline to a peak of 1.18. This association persisted when using alternative definitions of the duration of economic depression in sensitivity analyses. Once the period of economic depression was over, the male:female ratio returned to the baseline value. These data suggest that, in Cuba, contrary to the Trivers-Willard hypothesis, the human population responded to conditions of scarcity by increasing the ratio of males to females at livebirth. These data may be relevant in the modeling of demographic projections in countries that experience prolonged economic depression and in understanding adaptive human reproductive responses to environmental change. PMID- 22038103 TI - Invited commentary: Natural versus unnatural sex ratios--a quandary of modern times. AB - The typical dilemma with sex-ratio findings is that when they are real, they aren't interesting, and when they are interesting, they aren't real. In this issue of the Journal, Fernandez et al. (Am J Epidemiol. 2011;174(12):1327-1331) describe a deviation of the sex ratio that is apparently both large and real. There was a temporary but distinct spike in the proportion of boys born in Cuba around the time of the collapse of the national economy during the 1990s. Although an excess of boys does not fit the prevailing biologic theory regarding maternal stress and the sex ratio, the data are consistent with results from the Dutch famine (where population-level deprivation was even more extreme). A new quandary arises in the modern era with interpretation of the sex ratio: If the decision to abort a pregnancy is influenced by the sex of the fetus, a change in the behavior of even a small proportion of women could influence the sex ratio at birth. The possible role of sex selection in the Cuban context is discussed. PMID- 22038104 TI - Assessment of differential item functioning in the experiences of discrimination index: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. AB - The psychometric properties of instruments used to measure self-reported experiences of discrimination in epidemiologic studies are rarely assessed, especially regarding construct validity. The authors used 2000-2001 data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study to examine differential item functioning (DIF) in 2 versions of the Experiences of Discrimination (EOD) Index, an index measuring self-reported experiences of racial/ethnic and gender discrimination. DIF may confound interpretation of subgroup differences. Large DIF was observed for 2 of 7 racial/ethnic discrimination items: White participants reported more racial/ethnic discrimination for the "at school" item, and black participants reported more racial/ethnic discrimination for the "getting housing" item. The large DIF by race/ethnicity in the index for racial/ethnic discrimination probably reflects item impact and is the result of valid group differences between blacks and whites regarding their respective experiences of discrimination. The authors also observed large DIF by race/ethnicity for 3 of 7 gender discrimination items. This is more likely to have been due to item bias. Users of the EOD Index must consider the advantages and disadvantages of DIF adjustment (omitting items, constructing separate measures, and retaining items). The EOD Index has substantial usefulness as an instrument that can assess self-reported experiences of discrimination. PMID- 22038105 TI - Work-related violence and incident use of psychotropics. AB - Although the mental health consequences of domestic violence are well documented, empirical evidence is scarce regarding the mental health effects of violence in the workplace. Most studies have used data from small occupation-specific samples, limiting their generalizability. This article examines whether direct exposure to work-related violence is associated with clinically pertinent mental health problems, measured by purchases of psychotropics (antidepressants, anxiolytics, hypnotics), in a cross-occupational sample of 15,246 Danish employees free from using psychotropics at baseline. Self-reported data on work related violence were merged with other data on purchases of medications through a national registry to estimate cause-specific hazard ratios during 3.6 years (1,325 days) of follow-up in the years 1996-2008. Outcomes were examined as competing risks, and analyses were adjusted for gender, age, cohabitation, education, income, social support from colleagues, social support from supervisor, and influence and quantitative demands at work. Work-related violence was associated with purchasing antidepressants alone (hazard ratio = 1.38, 95% confidence interval: 1.09, 1.75) or in combination with anxiolytics (hazard ratio = 1.74, 95% confidence interval: 1.13, 2.70) but not with purchasing anxiolytics or hypnotics only. The frequency of violent episodes and risk of caseness were unrelated. Work-related violence is associated with increased risk of clinically pertinent mental health problems. Reducing levels of work-related violence may help to prevent mental disorders in the working population. PMID- 22038106 TI - Relation of plasma catecholamine levels with pulse wave velocity in hypertensive patients compared with normotensive subjects. AB - Although the circadian variation of catecholamine has been reported, that of the pulse wave velocity (PWV) has not. Brachial ankle (ba) PWV is associated with well-established indices of central stiffness. It is not known whether arterial stiffness is associated with catecholamine. The aim of the present study was to evaluate the changes in baPWV and those on the plasma epinephrine and norepinephrine levels in the morning and evening in hypertensive patients (HPs) and normotensive subjects (NSs). The baPWV and blood pressure (BP) were measured in 14 NSs (14 males, 39 +/- 5 years) and 10 HPs (9 males and 1 female, 55 +/- 13 years) at 06:00 h, noon, 18:00 h, and midnight, respectively. The plasma epinephrine and norepinephrine levels were measured in 14 NSs and 5 HPs at 06:00 h and 18:00 h, respectively. There was no significant difference in BPs at 06:00 h, noon, 18:00 h, and midnight in either NSs or HPs. The baPWV at 06:00 h was significantly lower than that at noon, 18:00 h, and midnight in NSs (P = 0.01, 0.04, and 0.0008, respectively). The plasma epinephrine and norepinephrine levels at 06:00 h were markedly lower than those at 18:00 h in NSs (P = 0.002 and 0.003, respectively). There were no significant changes in the baPWV of HPs at 06:00 h, noon, 18:00 h, or midnight. The plasma epinephrine and norepinephrine levels at 06:00 h were notably lower than those at 18:00 h in HPs (P = 0.004 and 0.01, respectively). Only NSs showed a significant reduction in the baPWV with a decrease in the plasma catecholamine levels in the morning, suggesting that the baPWV of NSs may be correlated with the variation of the plasma catecholamine levels. PMID- 22038107 TI - A novel atherogenic epitope from Mycobacterium tuberculosis heat shock protein 65 enhances atherosclerosis in rabbit and LDL receptor-deficient mice. AB - Previous studies have established that Mycobacterium tuberculosis heat shock protein 65 (mHSP65) plays an important role in immune-associated diseases as an autoimmune factor. Some overlapping epitopes of mHSP65 may serve as initiators of both atherosclerosis and other autoimmune-associated diseases. In the present study, atherosclerosis was significantly enhanced in high-cholesterol diet (HCD) fed New Zealand white rabbits immunized with mHSP65(91-105) compared with PBS immunized or BSA-immunized rabbits. Immunizing wild-type C57BL/6J mice with mHSP65(91-105) induced the aortic endothelial injury. Although western blot demonstrated that specific antibodies against mHSP65(91-105) can cross-react with recombinant human heat shock protein 60, specific antibodies against mHSP65(91 105) had no direct effects on HUVECs in vitro. Laser scanning confocal microscopy showed that mHSP65(91-105) localized in the cytoplasm of HUVECs, even when HUVECs were heat shocked at 42 degrees C. mHSP65(91-105)-specific splenic cells secreted more IFN-gamma than controls. Also, adoptive transfer of mHSP65(91-105)-specific splenic cells can accelerate atherosclerosis in ldlr( -/- ) mice. We can conclude that the (auto)immune response to mHSP65(91-105) accelerates atherosclerosis in animal models, and that the response of Th1 plays an important role in this progress. PMID- 22038108 TI - Effects of erythropoietin on angiogenesis after myocardial infarction in porcine. AB - Erythropoietin (EPO) has recently been shown to confer cardioprotective effects via angiogenesis and antiapoptosis. The administration of EPO after myocardial infarction (MI) reduces infarct size and improves cardiac function in small animals. The purpose of this study is to investigate the protective effects of EPO in porcine MI. Each animal in the EPO group received four injections of recombinant human EPO (rhEPO; 6000 U per injection) at 2-day intervals, starting after coronary occlusion. Animals in the control group received saline. Left ventriculography was performed just after coronary occlusion and at 28 days. Time course changes in serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and fibroblast growth factor (FGF) were measured. The number of vessels was calculated, and the mRNA expressions of VEGF and insulin-like growth factor (IGF) were examined. Left ventricular function was similar between the groups. The numbers of cells positive for anti-alpha-smooth muscle actin, von Willebrand factor, and c-kit were significantly higher in the EPO group than in the controls (P < 0.05). The EPO group exhibited significantly higher HGF and FGF concentrations (P < 0.05) and higher expression of VEGF and IGF mRNA (P < 0.05) compared with the controls. In conclusion, EPO accelerates angiogenesis via the upregulation of systemic levels such as HGF and FGF, and the local expression of VEGF and IGF, in porcine MI. PMID- 22038109 TI - Assessment of optimum stent deployment by stent boost imaging: comparison with intravascular ultrasound. AB - Stent boost (SB) imaging is an enhancement of the radiologic edge of the stent by digital management of regular X-ray images. The purpose of the present study was to validate SB imaging by comparison with the anatomical standard using intravascular ultrasound (IVUS). We investigated SB and IVUS after stent implantation in 68 arteries in 60 patients. Based on those findings, we added high-pressure dilatation in four patients and another stent implantation in four patients. We defined the SB criteria for adequate stent deployment as: complete stent expansion, stent minimum diameter >=70% of reference diameter, and stent minimum diameter >=2.0 mm; and IVUS criteria for adequate stent deployment as: minimal stent area >=5.0 mm(2). If the reference vessel was <2.8 mm, adequate stent deployment was defined as minimum stent area >=4.5 mm(2). IVUS findings indicated inadequate stent deployment in 21/72 observations (29%). Seven SB images showed inadequate stent expansion. SB predicted inadequate findings of IVUS with 100% specificity, 33% sensitivity, and 81% agreement. Although the sensitivity of SB image for adequate stent deployment is low, the specificity is sufficiently high for it to be the first-line for monitoring just after stent implantation in centers where IVUS is not used routinely. PMID- 22038110 TI - Vaccination against pandemic H1N1 (2009) in patients after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. AB - PURPOSE: Limited data are available on immunologic responses to primary pandemic H1N1 (2009) vaccination in recipients of allogeneic hematopoietic stem cell transplantation (HSCT) recipients. In 2009 serologic responses to either pandemic H1N1 (2009) vaccine (n = 36) or pandemic H1N1 (2009) infection (n = 2) were studied in 38 HSCT recipients. METHODS: Responses were measured with a standard hemagglutination-inhibition assay. Fourteen patients had active chronic graft versus-host disease (cGvHD) at the time of vaccination/infection and seven patients had cGvHD in remission; 11 patients had no immunosuppressive therapy, and 27 patients were on immunosuppressive therapy. Nineteen patients (53%) responded to pandemic H1N1 (2009) vaccination. Two patients had pandemic H1N1 (2009) infection without prior vaccination, and one patient had severe pandemic H1N1 (2009) infection with acute respiratory distress syndrome despite prior single vaccination. RESULTS: Non-responders to pandemic H1N1 (2009) vaccination more often had cGvHD (65 vs. 53%) and received second- or third-line therapy (53 vs. 11%), while responders mostly had first-line therapy for cGvHD. While vaccine responders had no or single agent immunosuppressive therapy, non-responders frequently received moderate or intense immunosuppressive therapy. All vaccine recipients previously treated with rituximab were non-responders. CONCLUSIONS: In summary, the overall response to pandemic H1N1 (2009) vaccination in HSCT recipients was modest. Patients receiving combined immunosuppressive therapy for steroid-refractory cGvHD barely responded to pandemic H1N1 (2009) vaccination. PMID- 22038111 TI - Mycobacterium szulgai: an unusual cause of disseminated mycobacterial infections. PMID- 22038112 TI - Molecular epidemiology and the clinical significance of Acinetobacter baumannii complex isolated from cerebrospinal fluid in neurosurgical intensive care unit patients. AB - OBJECTIVE: This study was intended to investigate the clinical significance and molecular epidemiology of Acinetobacter baumannii complex (ABC) isolated from cerebrospinal fluid (CSF) in neurosurgical intensive care unit (NSICU) patients, particularly comparing isolates from healthcare workers' (HCW) hands. METHODS: We retrospectively reviewed the medical records of 30 patients with CSF cultures positive for ABC seen at our NSICU from the date it first opened, January 2007, to September 2010. Pulsed-field gel electrophoresis (PFGE) typing was performed on 68 strains isolated from 32 patients' CSF and 36 HCWs' hands. RESULTS: ABC isolates were considered to be clinically significant in 21 (70.0%) patients but insignificant in the other nine (30.0%) patients. The prolonged (>7 days) use of cephalosporins was more common in patients with clinically significant ABC isolates (p = 0.049). Multiple drug resistance (MDR) was observed in 12 (57.1%) clinically significant isolates. Empirical antimicrobial therapies were not appropriate for nine of these 21 patients (42.8%). Mortality was significantly higher in the clinically significant group than in the clinically insignificant group (18/21 vs. 3/9; p = 0.008). Fifty-three isolates (77.9%) were grouped into 15 clusters, three of which contained possibly related isolates from patients' CSF and staff members' hands. CONCLUSIONS: The fact that ABC isolates grown from CSF cultures do not always exhibit infection and have high multiple antibiotic resistance, including to carbapenems, should be borne in mind when planning treatment for these patients. In addition, HCWs' hands may play a significant role in transmission to patients, and compliance with infection control procedures, especially hand washing, must be enhanced in order to avoid ABC infections. PMID- 22038113 TI - Rhizobium radiobacter bacteremia in a neonate. AB - Rhizobium radiobacter bacteremia is an infrequent cause of human infection. We report a rare manifestation of R. radiobacter infection in which bacteremia occurred in a newborn infant without other risk factors. PMID- 22038114 TI - Readability of patient-reported outcome questionnaires for use with persons with swallowing disorders. AB - The purposes of this study were to examine the readability of published patient related outcome (PRO) questionnaires for persons with swallowing problems, and to compare the readability results to existing data about average reading levels of English-speaking adults living in the United States. A search was conducted to identify published PRO questionnaires related to swallowing problems that traditionally are completed by patients in a self-administered format. Reading grade levels were analyzed separately for four different swallowing-related PRO questionnaires using the Flesch Reading Ease, FOG, and FORCAST formulas as computed by a readability calculations software package. Descriptive statistics were also computed across the questionnaires. The results of this study demonstrate that all four PRO questionnaires exceeded the fifth- to sixth-grade reading levels recommended by health literacy experts regardless of the formula applied. In the demand for standardization of swallowing-related quality-of-life assessment tools, developers should consider readability as another testable construct, since poor readability may affect validity, reliability, and sensitivity. The swallowing clinician should consider the average reading level needed to understand a particular PRO questionnaire when administering it to a patient or his or her proxy. Developers of PRO questionnaires should consider the reading level of respondents and include information about this when reporting psychometric data. PMID- 22038115 TI - Identification of GABRA1 and LAMA2 as new DNA methylation markers in colorectal cancer. AB - Aberrant methylation of CpG islands in the promoter region of genes is a common epigenetic phenomenon found in early cancers. Therefore conducting genome-scale methylation studies will enhance our understanding of the epigenetic etiology behind carcinogenesis by providing reliable biomarkers for early detection of cancer. To discover novel hypermethylated genes in colorectal cancer by genome wide search, we first defined a subset of genes epigenetically reactivated in colon cancer cells after treatment with a demethylating agent. Next, we identified another subset of genes with relatively down-regulated expression patterns in colorectal primary tumors when compared with normal appearing adjacent regions. Among 29 genes obtained by cross-comparison of the two gene sets, we subsequently selected, through stepwise subtraction processes, two novel genes, GABRA1 and LAMA2, as methylation targets in colorectal cancer. For clinical validation pyrosequencing was used to assess methylation in 134 matched tissue samples from CRC patients. Aberrant methylation at target CpG sites in GABRA1 and LAMA2 was observed with high frequency in tumor tissues (92.5% and 80.6%, respectively), while less frequently in matched tumor-adjacent normal tissues (33.6% for GABRA1 and 13.4% for LAMA2). Methylation levels in primary tumors were not significantly correlated with clinico-pathological features including age, sex, survival and TNM stage. Additionally, we found that ectopic overexpression of GABRA1 in colon cancer cell lines resulted in strong inhibition of cell growth. These results suggest that two novel hypermethylated genes in colorectal cancer, GABRA1 and LAMA2, may have roles in colorectal tumorigenesis and could be potential biomarkers for the screening and the detection of colorectal cancer in clinical practice. PMID- 22038116 TI - C-reactive protein and nitric oxide levels in ischemic stroke and its subtypes: correlation with clinical outcome. AB - Studies in different populations have shown that ischemic stroke can trigger an acute phase response resulting in a rise of plasma concentration of C-reactive protein (CRP). However, there are very limited studies on CRP and first ischemic stroke divided into subtypes. High levels of CRP may also be associated with poor outcome. The present study was taken up to investigate the prognostic value of CRP within 24 h of onset of ischemic stroke. Five hundred and eighty one patients with first stroke and 575 age- and sex-matched healthy controls were involved in the study. High-sensitivity C-reactive protein (hsCRP) levels were estimated, and follow-up interviews were conducted with patients at 3, 6, and 12 months post event to determine stroke outcome. In addition to this plasma, NO( x ) (nitrate and nitrite) was measured to detect the serum NO (an important biomarker of inflammation and oxidative stress) levels in ischemic stroke patients and controls. The relationship between CRP value and poor outcome (>2 on modified Rankin Scale Score and <5 on an extended Glasgow outcome scale) was studied. There was a significant association between elevated levels of CRP and NO with the disease. A stepwise multiple logistic regression analysis confirmed these findings after adjustment for potential confounders [adjusted odds ratio = 2.890, 95% CI (1.603-5.011) with p < 0.01 and adjusted odds ratio = 2.364, 95% CI (1.312 3.998) with p < 0.01 for hsCRP and NO, respectively]. After adjustment of potential confounders, patients with high CRP levels had a significant increased risk of poor outcome [adjusted odds ratio = 3.50, 95% CI (1.312-6.365) and p < 0.001]. Elevated levels of hsCRP associated significantly with all stroke subtypes classified according to Trial of ORG 10172 in Acute Stroke Treatment classification except for lacunar stroke and stroke of other determined etiology. In conclusion, hsCRP and NO levels predict the incidence of ischemic stroke and hsCRP is an independent prognostic factor of poor outcome at 3 months. PMID- 22038117 TI - Engineering aspects of biological ion channels--from biosensors to computational models for permeation. AB - This paper presents two important engineering aspects of biological ion channels how to build sensors out of gramicidin channels and how to construct computational models for ion channel permeation. We describe our recent research in these areas, potential challenges and possible solutions. PMID- 22038118 TI - Co-expression of VpROMT gene from Chinese wild Vitis pseudoreticulata with VpSTS in tobacco plants and its effects on the accumulation of pterostilbene. AB - Plant secondary metabolites, such as stilbenes, have fungicidal potential and have been found in several plant species. Stilbenes in grapevine, such as resveratrol and pterostilbene, have recently attracted much attention, they are not only helping the plant to fight against pathogen attack, but they are also being widely used as ingredients of fungicide, anti-inflammatory drugs, antioxidant, and anti-infective agents. However, resveratrol O-methyltransferase gene, related with the synthesis of pterostilbene from resveratrol, has not been characterized effectively from Chinese wild Vitis pseudoreticulata. In this study, a candidate of resveratrol O-methyltransferase gene designated as VpROMT was isolated from a powdery mildew-resistant Chinese wild V. pseudoreticulata 'Baihe-35-1', and characterization studies were performed. Expression studies showed that VpROMT was predominantly expressed in developing roots yet not found in the leaves, stems, nor tendrils when the plants are not challenged. Results of qRT-PCR showed that VpROMT was rapidly induced by Erysiphe necator in V. pseudoreticulata and by methyl-jasmonate, UV-irradiation in suspension culture cells of Vitis romanetii. The expression level varies in different tissues of grapevine, which MeJA and UV-C treatment significantly upregulated the expression of VpROMT gene while UV-B treatment failed to. Co-expression of VpROMT and grapevine stilbene synthase (VpSTS) gene leads to the accumulation of pterostilbene in leaves of tobacco (Nicotiana tabacum) indicating that VpROMT was able to catalyze the biosynthesis of pterostilbene from resveratrol in over expression transgenic tobacco plants. PMID- 22038120 TI - Limitations of conventional inhibitor classifications. AB - Enzyme inhibitors are usually classified as competitive, non-competitive or mixed non-competitive. Each of these designations has a serious limitation in that it only describes an extreme of inhibitory behaviour. The non-competitive inhibition equation only considers an approach to complete inhibition of the catalytic turnover rate, while the competitive inhibition equation predicts an infinite increase in the Michaelis-Menten constant (decrease in enzyme affinity for substrate), resulting from increased inhibitor concentration. Both of these models exclude the possibility of a finite inhibitor-induced change in the kinetic parameters of the enzyme they are affecting. They also exclude the possibility of an inhibitor affecting both the substrate affinity and the catalytic turnover at the same time. Mixed non-competitive inhibition describes a hybrid form of inhibition displaying some characteristics of both competitive and non-competitive inhibition. It also suffers from an inability to describe finite changes in activity and to describe concomitant changes in substrate affinity and catalytic turnover. Two inhibitor binding constants are invoked in this equation, suggesting that such inhibitors interact with the enzyme in two completely independent manners. From these considerations, it is suggested here that conventional equations do not adequately describe observed kinetic data due to a lack of distinction between the mass action binding term describing inhibitor enzyme association and the terms representing the actual effect of the inhibitor on the enzyme. Herein we describe an alternate approach for representing enzyme activity modulation based on a re-examination of conventional inhibition equations. The arguments presented are illustrated using the known competitive inhibition of Kallikrein with benzamidine. PMID- 22038119 TI - Functions of the Arabidopsis kinesin superfamily of microtubule-based motor proteins. AB - Plants possess a large number of microtubule-based kinesin motor proteins. While the kinesin-2, 3, 9, and 11 families are absent from land plants, the kinesin-7 and 14 families are greatly expanded. In addition, some kinesins are specifically present only in land plants. The distinctive inventory of plant kinesins suggests that kinesins have evolved to perform specialized functions in plants. Plants assemble unique microtubule arrays during their cell cycle, including the interphase cortical microtubule array, preprophase band, anastral spindle and phragmoplast. In this review, we explore the functions of plant kinesins from a microtubule array viewpoint, focusing mainly on Arabidopsis kinesins. We emphasize the conserved and novel functions of plant kinesins in the organization and function of the different microtubule arrays. PMID- 22038121 TI - Bio-protective effects of homologous disaccharides on biological macromolecules. AB - In this contribution the effects of the homologous disaccharides trehalose and sucrose on both water and hydrated lysozyme dynamics are considered by determining the mean square displacement (MSD) from elastic incoherent neutron scattering (EINS) experiments. The self-distribution function (SDF) procedure is applied to the data collected, by use of IN13 and IN10 spectrometers (Institute Laue Langevin, France), on trehalose and sucrose aqueous mixtures (at a concentration corresponding to 19 water molecules per disaccharide molecule), and on dry and hydrated (H(2)O and D(2)O) lysozyme also in the presence of the disaccharides. As a result, above the glass transition temperature of water, the MSD of the water-trehalose system is lower than that of the water-sucrose system. This result suggests that the hydrogen-bond network of the water-trehalose system is stronger than that of the water-sucrose system. Furthermore, by taking into account instrumental resolution effects it was found that the system relaxation time of the water-trehalose system is longer than that of the water-sucrose system, and the system relaxation time of the protein in a hydrated environment in the presence of disaccharides increases sensitively. These results explain the higher bioprotectant effectiveness of trehalose. Finally, the partial MSDs of sucrose/water and trehalose/water have been evaluated. It clearly emerges from the analysis that these are almost equivalent in the low-Q domain (0-1.7 A(-1)) but differ substantially in the high-Q range (1.7-4 A(-1)). These findings reveal that the lower structural sensitivity of trehalose to thermal changes is connected with the local spatial scale. PMID- 22038122 TI - Adhesion and stress relaxation forces between melanoma and cerebral endothelial cells. AB - Mechanical parameters play a crucial role in proper cellular functions. This article examines the process of the appearance and breaking of adhesion forces during contact between the confluent cerebral endothelial cell layer and a melanoma cell attached to a tipless cantilever. This adhesion is the initial phase of melanoma transmigration through the endothelial cell layer. Taking the force measurement, if the contact was prolonged for several seconds, a decrease in the load force was observed, which corresponds to stress relaxation of the cells. The dependence of adhesion force and stress relaxation on dwell time showed a saturation-like behavior. These stress relaxation curves could be fitted with the sum of two exponentials, suggesting that two independent processes take place simultaneously. The breakup of the adhesion during the retraction of the cantilever with the attached melanoma cell is not continuous but shows jumps. Between living endothelial and melanoma cells, a minimum jump size of about 20 pN could be determined. The minimum jump is independent of the dwell time and load force. It seems to be the elementary binding force between these two cell types. In case of fixed endothelial cells, the adhesion force was strongly decreased and the jumps disappeared, whereas the stress relaxation did not show considerable change upon fixation. PMID- 22038123 TI - Acoustic levitation: recent developments and emerging opportunities in biomaterials research. AB - Containerless sample environments (levitation) are useful for study of nucleation, supercooling, and vitrification and for synthesis of new materials, often with non-equilibrium structures. Elimination of extrinsic nucleation by container walls extends access to supercooled and supersaturated liquids under high-purity conditions. Acoustic levitation is well suited to the study of liquids including aqueous solutions, organics, soft materials, polymers, and pharmaceuticals at around room temperature. This article briefly reviews recent developments and applications of acoustic levitation in materials R&D. Examples of experiments yielding amorphous pharmaceutical materials are presented. The implementation and results of experiments on supercooled and supersaturated liquids using an acoustic levitator at a high-energy X-ray beamline are described. PMID- 22038124 TI - Genotyping of Haemophilus influenzae type b in pre-vaccination era. AB - Identification of Haemophilus influenzae type b (Hib) in asymptomatic carriers is critical to control the spread of disease. This study was conducted between January 2008 and August 2011 as part of a birth cohort study in Sado Island, Japan, to elucidate the prevalence of Hib and its clones in a specific region. Nasopharyngeal cultures were obtained from 349 subjects at 4-, 7-, 10-, 18-, and 36-month health checkups and analyzed for H. influenzae. The Hib and nontypeable H. influenzae detection rates ranged from 0 to 1.5% (12 isolates) and from 7.9 to 32.9%, respectively. Twelve pediatric patients diagnosed with invasive or non invasive Hib infections during the study period were also enrolled. The Hib isolates were analyzed for carriage of the beta-lactamase gene and ftsI mutations, and multilocus sequence type (MLST, ST type). Of the 24 Hib isolates, 18 (75%) were ST54, 5 (21%) were ST190, and 1 isolate (4%) was ST95. All of the ST190 isolates were genetically beta-lactamase-negative ampicillin-susceptible isolates, while all but one of the ST54 isolates were genetically beta-lactamase positive amoxicillin/clavulanic acid-resistant isolates. The geographic distribution of Hib isolates in the study period was scattered. There were 2 day care cases and 1 family case of Hib infection. The ST54 and ST190 strains circulated in Sado Island and were detected in both asymptomatic carriers and patients. We note that surveillance of healthy subjects to identify Hib carriers is important to understand the transmission of Hib. PMID- 22038125 TI - Vigorous cleaning and adequate ventilation are necessary to control an outbreak in a neonatal intensive care unit. AB - An outbreak of Bacillus cereus (B. cereus) bacteremia occurred in our neonatal intensive care unit (NICU) in July 2005. Many strains of B. cereus were cultured from patient specimens, as well as from environmental samples such as the surfaces of instruments and air in the NICU. Some of these strains were analyzed by pulsed field gel electrophoresis, and several were confirmed to be identical. We speculated that the bacterial load in the environment had initially increased and then possibly spread throughout the NICU facility via the airflow of the ventilation system. For this reason, besides maintaining standard precautions, we performed a vigorous clean of the NICU, and covered the vents to prevent dust falling from them. These protective measures ended the outbreak. In the hospital environment, adequate ventilation is important, especially in single-occupancy isolation rooms and operating theaters. However, the criteria for the adequate ventilation of multioccupancy rooms for acute care environments such as the NICU have not yet been defined. We need to pay more attention to these environmental factors in order to avoid cross contamination and infectious outbreaks. PMID- 22038126 TI - Health care access and utilization among US-born and foreign-born Asian Americans. AB - Despite efforts to eliminate inequality in health and health care, disparities in health care access and utilization persist in the United States. The purpose of this study was to compare the access to care and use of health care services of US-born and foreign-born Asian Americans. We used aggregated data from the National Health Interview Survey (NHIS) from 2003 to 2005, including 2,500 participants who identified themselves as Asian. Associations between country of birth and reported access and utilization of care in the previous 12 months were examined. After controlling for covariates, being foreign-born was negatively related to indicators of access to care, including health insurance (OR = 0.29, 95%CI = 0.18-0.48), routine care access (OR = 0.52, 95%CI = 0.36-0.75), and sick care access [OR = 0.67, 95%CI = 0.47-0.96)]. Being foreign-born was also negatively related to all indicators of health care utilization (office visit: OR = 0.58, 95%CI = 0.41-0.81; seen/talked to a general doctor: OR = 0.69, 95%CI = 0.52-0.90; seen/talked to a specialist: OR = 0.42, 95%CI = 0.28-0.63) but ER visit (OR = 0.84, 95%CI = 0.59-1.20). There are substantial differences by country of birth in health care access and utilization among Asian Americans. Our findings emphasize the need for developing culturally sensitive health services and intervention programs for Asian communities. PMID- 22038127 TI - A novel function of Streptomyces integration host factor (sIHF) in the control of antibiotic production and sporulation in Streptomyces coelicolor. AB - Bacterial integration host factors (IHFs) play important roles in site-specific recombination, DNA replication, transcription, genome organization and bacterial pathogenesis. In Streptomyces coelicolor, there are three putative IHFs: SCO1480, SCO2950 and SCO5556. SCO1480 or Streptomyces IHF (sIHF) was previously identified as a transcription factor that binds to the promoter region of redD, the pathway specific regulatory gene for the undecylprodigiosin biosynthetic gene cluster. Here we show that production of the pigmented antibiotics actinorhodin and undecylprodigiosin is strongly enhanced in sihf null mutants, while sporulation was strongly inhibited, with an on average 25% increase in spore size. Furthermore, the sihf mutant spores showed strongly reduced viability, with high sensitivity to heat and live/dead staining revealing a high proportion of empty spores, while enhanced expression of sIHF increased viability. This suggests a major role for sIHF in controlling viability, perhaps via the control of DNA replication and/or segregation. Proteomic analysis of the sihf null mutant identified several differentially expressed transcriptional regulators, indicating that sIHF may have an extensive response regulon. These data surprisingly reveal that a basic architectural element conserved in many actinobacteria such as mycobacteria, corynebacteria, streptomycetes and rhodococci may act as a global regulator of secondary metabolism and cell development. PMID- 22038128 TI - Compositions of microbial communities associated with oil and water in a mesothermic oil field. AB - Samples of produced water and oil obtained from the Enermark field (near Medicine Hat, Alberta, Canada) were separated into oil and aqueous phases first gravitationally and then through centrifugation at 20 degrees C in an atmosphere of 90% N(2) and 10% CO(2). Biomass that remained associated with oil after gravitational separation (1*g) was dislodged by centrifugation at 25,000*g. DNA was isolated from the aqueous and oil-associated biomass fractions and subjected to polymerase chain reaction amplification with primers targeting bacterial and archaeal 16S rRNA genes. DNA pyrosequencing and bioinformatics tools were used to characterize the resulting 16S rRNA gene amplicons. The oil-associated microbial community was less diverse than that of the aqueous phase and had consistently higher representation of hydrogenotrophs (methanogens of the genera Methanolobus and Methanobacterium and acetogens of the genus Acetobacterium), indicating the oil phase to be a primary source of hydrogen. Many known hydrocarbon degraders were also found to be oil-attached, e.g. representatives of the gammaproteobacterial genus Thalassolituus, the actinobacterial genus Rhodococcus and the alphaproteobacterial genera Sphingomonas, Brevundimonas and Stappia. In contrast, all eight representatives of genera of the Deltaproteobacteria identified were found to be associated with the aqueous phase, likely because their preferred growth substrates are mostly water-soluble. Hence, oil attachment was seen for genera acting on substrates found primarily in the oil phase. PMID- 22038129 TI - Isolation and characterization of culturable endophytic actinobacteria associated with Artemisia annua L. AB - Endophytic actinobacteria isolated from Artemisia annua were characterized and evaluated for their bioactivities. A total of 228 isolates representing at least 19 different genera of actinobacteria were obtained and several of them seemed to be novel taxa. An evaluation of antimicrobial activity showed that more isolates possessed activity towards plant pathogens than activity against other pathogenic bacteria or yeasts. High frequencies of PCR amplification were obtained for type I polyketide synthases (PKS-I, 21.1%), type II polyketide synthases (PKS-II, 45.2%) and nonribosomal peptide synthetases (NRPS, 32.5%). The results of herbicidal activity screening indicated that 19 out of 117 samples of fermentation broths completely inhibited the germination of Echinochloa crusgalli. This study indicated that endophytic actinobacteria associated with A. annua are abundant and have potentially beneficial and diverse bioactivities which should be pursued for their biotechnical promise. PMID- 22038130 TI - Survival and biofilm formation by Group B streptococci in simulated vaginal fluid at different pHs. AB - The Group B Streptococcus (GBS, Streptococcus agalactiae) is an important cause of neonatal and maternal infection. GBS is a commensal organism of the lower gastrointestinal and vaginal tract. A frequent mode of neonatal infection is vertical transmission from pregnant women to their foetus or neonate. The aim of this study was to evaluate the survival and biofilm production of 10 GBS strains in simulated vaginal fluid at pH 4.2, 5.5 and 6.5. GBS survived longer at higher pH than at normal vaginal pH. At pH 4.2, with the exception of two isolates that were recovered up to 48 and 72 h, viable GBS numbers declined below the limit of detection by 24 h. At higher pH, GBS survived between 3 and 15 days. All isolates investigated were biofilm producers but biofilm production was greater in tryptone soy broth compared to simulated vaginal fluid. The quantity of biofilm produced increased with the rise in the pH. This study suggests that high vaginal pH may influence both GBS survival and biofilm production and thus could be a risk factor for GBS infection. PMID- 22038131 TI - [HPV-induced diseases of the female genital tract]. PMID- 22038132 TI - [HPV-associated carcinomas of the female genital tract. Molecular mechanisms of development]. AB - Infections with human papillomaviruses (HPV) are a common occurrence in both men and women. In contrast HPV-associated neoplasias are relatively rare and occur only in certain areas of the body. The virus has obviously developed efficient mechanisms for its persistence without inducing too much damage to the host. The formation of neoplasia seems to be more an exception. Epigenetic mechanisms play an important role in the regulation of viral gene expression. Investigations have indicated that exactly the transition from the permissive infection stage to a transformation stage, where neoplastic alterations can occur due to expression of the viral oncogenes, is associated with certain methylation patterns of the viral genome which promote the expression of the oncogenes E6 and E7. The transforming stage is seen as the actual carcinogenic event and can be immunohistochemically detected by the biomarker p16(INK4a). PMID- 22038134 TI - [Computer-assisted diagnostics in cervical cytology]. AB - Computer assistance has the ability to reduce screening errors. In cervical cytology only two systems are available: BD FocalPointTM (BD) utilizes algorithms for image recognition to analyze thin-layer specimens (Surepath) and conventional slides. The ThinPrep(r) imaging system (Hologic) is based on the densitometric measurement of nuclei and requires a thin-layer preparation. The BD FocalPointTM system assigns specimens according to declining probability of an abnormality to one of six groups. A further option is location-guided screening (LGS) where the 15 fields of view which are most relevant are presented on a computerized microscope. Several studies indicate that this mode is at least equivalent to manual screening with conventional and surepath (SP) slides. For the ThinPrep(r) imaging system which only uses the LGS mode the majority of available studies found a significantly higher sensitivity for histologically confirmed grade 2 cervical intraepithelial neoplasia (CIN 2 +). However, most were retrospective or parallel studies. Both systems allow a significantly higher productivity but require a higher technical expenditure. PMID- 22038135 TI - [Diagnosis and differential diagnosis of cervical adenocarcinoma]. AB - This overview summarizes pathogenetic and practical aspects of (sub )classification of cervical glandular (pre-)neoplasias and, inter alia, calls into question the usefulness of grading. In the context of the differential diagnosis of benign "imitations", the phenotypic variability of glandular precancerous lesions and carcinomas is described as well as the use of special tests to distinguish them. With regard to carcinomas, the differential diagnosis of well-differentiated neoplasias is addressed including "minimal deviation" adenocarcinoma (MDA, malignant adenoma), carcinomas with endometrioid or villoglandular morphology, and mesonephric hyper- and neoplasias. Furthermore, knowledge of HPV-negative glandular (pre-)neoplasias is covered including "gastric-type" adenocarcinomas and diagnostic algorithms for discriminating between primary and secondary cervical adenocarcinomas. Finally, comments are offered on the difficulties in recognizing early invasive adenocarcinomas, especially also the pitfalls inherent in determining the depth of invasion. PMID- 22038133 TI - [HPV-associated alterations of the vulva and vagina. Morphology and molecular pathology]. AB - Non-neoplastic HPV-induced alterations of the vulva and vagina are frequent. The traditional three-tier grading system of vulvar intraepithelial neoplasia (VIN) will be replaced by the definition of usual and simplex type of VIN. The usual type is characterized by a strong association to high-risk HPV infections, the occurrence at younger age and multifocality, mostly associated with non keratinizing squamous cell carcinoma. The differentiated (or simplex) type is rare and shows an association to older age and p53 alterations and is typically diagnosed co-incidentally with keratinizing squamous cell carcinoma. Vaginal intraepithelial neoplasia (VAIN) is still graded into VAIN 1-3 where VAIN 1 and 2 are mostly associated with low-risk HPV infections and a high spontaneous regression rate whereas VAIN 3 represents a high-risk HPV-associated lesion with capable progression into (micro-)invasive carcinoma. The differential diagnosis between a non-neoplastic condylomatous lesion and VIN common type and VAIN may be aided by p16 immunohistochemistry. The HPV-associated invasive vulvo-vaginal cancers are verrucous carcinoma (low-risk HPV) and the high-risk HPV-induced (non keratinizing) squamous cell carcinoma (NOS), the condylomatous (warty) carcinoma and the very rare vaginal squamo-transitional carcinoma. PMID- 22038137 TI - Electronic effects in 1,3-dipolar cycloaddition reactions of N-alkyl and N-benzyl nitrones with dipolarophiles. AB - 1,3-Dipolar cycloadditions afforded fast access to isoxazolidines bearing N-alkyl or N-benzyl substituents. The electronic properties of the substituents in the nitrones define the activity of the dipoles and modulate diastereoselectivity in the non-catalyzed reactions. Using a chiral one-point binding ruthenium Lewis acid catalyst, products were obtained in good yields and with excellent regio-, diastereo-, and enantioselectivity. PMID- 22038138 TI - The rice bright green leaf (bgl) locus encodes OsRopGEF10, which activates the development of small cuticular papillae on leaf surfaces. AB - Development of specialized epidermal cells and structures plays a key role in plant tolerance to biotic and abiotic stresses. In the paddy field, the bright green leaf (bgl) mutants of rice (Oryza sativa) exhibit a luminous green color that is clearly distinguishable from the normal green of wild-type plants. Transmission and scanning electron microscopy revealed that small cuticular papillae (or small papillae; SP), nipple-like structures, are absent on the adaxial and abaxial leaf surfaces of bgl mutants, leading to more direct reflection and less diffusion of green light. Map-based cloning revealed that the bgl locus encodes OsRopGEF10, one of eleven OsRopGEFs in rice. RopGEFs (guanine nucleotide exchange factors for Rop) activate Rop/Rac GTPases, acting as molecular switches in eukaryotic signal transduction by replacing the bound GDP (inactive form) with GTP (active form) in response to external or internal cues. In agreement with the timing of SP initiation on the leaf epidermis, OsRopGEF10 is most strongly expressed in newly developing leaves before emergence from the leaf sheath. In yeast two-hybrid assays, OsRopGEF10 interacts with OsRac1, one of seven OsRac proteins; consistent with this, both proteins are localized in the plasma membrane. These results suggest that OsRopGEF10 activates OsRac1 to turn on the molecular signaling pathway for SP development. Together, our findings provide new insights into the molecular genetic mechanism of SP formation during early leaf morphogenesis. PMID- 22038139 TI - Screening of repeated dose toxicity data present in SCC(NF)P/SCCS safety evaluations of cosmetic ingredients. AB - Alternative methods, replacing animal testing, are urgently needed in view of the European regulatory changes in the field of cosmetic products and their ingredients. In this context, a joint research initiative called SEURAT was recently raised by the European Commission and COLIPA, representing the European cosmetics industry, with the overall goal of developing an animal-free repeated dose toxicity testing strategy for human safety assessment purposes. Although cosmetic ingredients are usually harmless for the consumer, one of the initial tasks of this research consortium included the identification of organs that could potentially be affected by cosmetic ingredients upon systemic exposure. The strategy that was followed hereof is described in the present paper and relies on the systematic evaluation, by using a self-generated electronic databank, of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. These findings are not only of relevance for the in vitro modeling efforts and choice of compounds to be tested in the SEURAT project cluster, but also demonstrate the importance of using previously generated toxicological data through an electronic databank for addressing specific questions regarding the safety evaluation of cosmetic ingredients. PMID- 22038140 TI - Effect of ziram on natural killer, lymphokine-activated killer, and cytotoxic T lymphocyte activity. AB - Ziram is a carbamate pesticide, which is widely used throughout the world as a fungicide in agriculture and as an accelerating agent in latex production. In the present study, we investigated the effect of ziram at 0.031-4 MUM in vitro on human natural killer (NK) and lymphokine-activated killer (LAK) and murine cytotoxic T lymphocyte (CTL) activity and found that it significantly inhibited all three activities in a concentration-dependent manner. To explore the mechanism of ziram-induced inhibition of NK activity, NK-92MI cells, a human NK cell line, were used. We previously confirmed that NK-92MI cells express CD56, perforin, granzyme (Gr) A, GrB, Gr3/K, and granulysin and are highly cytotoxic to K562 cells in the chromium release assay. NK-92MI cells were treated with ziram at 0.125-4 MUM for 4 or 16 h at 37 degrees C in vitro. Then, intracellular levels of perforin, GrA, GrB, Gr3/K, and granulysin were determined by flow cytometry. It was found that ziram significantly reduced Gr3/K, granulysin, perforin, GrA, and GrB levels. The extent of the decrease differed among the proteins, and the order was as follows: Gr3/K > granulysin > perforin, GrA, and GrB. Taken together, these findings suggest the ziram-induced inhibition of NK, LAK, and CTL activities to be at least partially mediated by decreases in the intracellular levels of Gr3/K, granulysin, perforin, GrA, and GrB. PMID- 22038141 TI - Pitavastatin, a new HMG-CoA reductase inhibitor, induces phototoxicity in human keratinocytes NCTC-2544 through the formation of benzophenanthridine-like photoproducts. AB - This study reports the results of an investigation of the phototoxicity mechanism induced by pitavastatin and its photoproducts, namely 6-cyclopropyl-10-fluoro-7,8 dihydrobenzo[k]phenanthridine (PP3) and 6-cyclopropyl-10 fluorobenzo[k]phenanthridine (PP4). The phototoxicity was tested in human keratinocytes cell lines NCTC-2544, and the results proved that under the same conditions, all three compounds exhibited phototoxic effects in the model tested. The reduction in cell viability was found to be both concentration- and UVA dose dependent. A point of note is that both the photoproducts produced a dramatic decrease in cell viability with GI(50) values one order of magnitude lower compared to the parent compound. In particular, the fully aromatic derivative (PP4) showed the highest antiproliferative activity. Flow cytometric analysis indicated that pitavastatin and the photoproduct PP4 principally induced necrosis, as revealed by the large appearance of propidium iodide-positive cells and also confirmed by the rapid drop in cellular ATP levels. Further studies committed to better understanding of photoinduced cell death mechanism(s) revealed that neither pitavastatin nor PP4 induced mitochondrial depolarization or lysosomal damage, but, interestingly, extensive cell lipid membrane peroxidation along with a significant oxidation of model proteins occurred, suggesting that pitavastatin and PP4 exert their phototoxic effect mainly in the cellular membranes. The present results suggest that the phototoxicity of pitavastatin may be mediated by the formation of benzophenanthridine-like photoproducts that appear to have high potential as photosensitizers. PMID- 22038142 TI - [On the track of the immune system (Nobel Prize)]. PMID- 22038143 TI - Evaluation of carotid wave intensity in firefighters following firefighting. AB - Sudden cardiac events are the leading cause of line-of-duty firefighter deaths, but little information exists elucidating the physiologic responses. Wave intensity (WI) is a new hemodynamic index that provides information about the dynamic behavior of the heart and the vascular system and their interaction. The larger first peak wave (W1) occurs during early systole and is associated with cardiac contractility. The second smaller peak (W2) follows a period of relatively little net wave (NA) production and may be caused by reflected waves from the brain. This study aimed at determining arterial WI changes in response to live firefighting activities. We examined the WI of 39 firefighters (2 females) with a mean age of 28 +/- 1 years and BMI of 26.6 +/- 0.7 kg m(-2) at rest, and immediately after 3 h of live firefighting drills. WI was assessed on the right common carotid artery using an Aloka high-resolution ultrasound. The magnitude of the W1 decreased significantly from 15,925 +/- 1,341 to 11,540 +/- 886 mmHg m s(-3), p < 0.05. The magnitude of W2 remained unchanged (W2: from 2,080 +/- 200 to 2,144 +/- 358 mmHg m s(-3)). Net NA decreased from 53 +/- 5 to 40 +/- 4 mmHg m s(-2). In conclusions, our data suggest that left ventricular function and arterial-ventricular coupling decreased following live firefighting, and this may be related to the documented increase in risk of clinical events during and after firefighting activities. PMID- 22038144 TI - Effect of heavy strength training on muscle thickness, strength, jump performance, and endurance performance in well-trained Nordic Combined athletes. AB - The purpose of the present study was to investigate the effect of supplemental heavy strength training on muscle thickness and determinants of performance in well-trained Nordic Combined athletes. Seventeen well-trained Nordic Combined athletes were assigned to either usual training supplemented with heavy strength training (STR; n = 8) or to usual training without heavy strength training (CON; n = 9). The strength training performed by STR consisted of one lower-body exercise and two upper-body exercises [3-5 repetition maximum (RM) sets of 3-8 repetitions], which were performed twice a week for 12 weeks. Architectural changes in m. vastus lateralis, 1RM in squat and seated pull-down, squat jump (SJ) height, maximal oxygen consumption (VO(2max)), work economy during submaximal treadmill skate rollerskiing, and performance in a 7.5-km rollerski time trial were measured before and after the intervention. STR increased 1RM in squat and seated pull-down, muscle thickness, and SJ performance more than CON (p < 0.05). There was no difference between groups in change in work economy. The two groups showed no changes in total body mass, VO(2max), or time-trial performance. In conclusion, 12 weeks of supplemental strength training improved determinants of performance in Nordic Combined by improving the athletes' strength and vertical jump ability without increasing total body mass or compromising the development of VO(2max). PMID- 22038145 TI - Human cardiac autonomic responses to head-up tilting during 72-h starvation. AB - Starvation may change autonomic nervous system activity and sensitivity such that a greater vagal withdrawal may occur during a sympathetic challenge. Six healthy humans endured a 3-day, water-only fast, during which participants were subjected to passive 80 degrees head-up tilt testing twice on each day (a.m. and p.m.). Heart rate, heart rate variability (HRV), ventilation [Formula: see text], and respiration ([Formula: see text] and [Formula: see text]) were recorded during supine rest and head-up tilting. On Day 1 (a.m.), supine heart rate was 46.0 +/- 3.3 beats min(-1), increasing to 51.6 +/- 7.4 beats min(-1) on Day 3 (p.m.). On Day 1 (a.m.), supine high frequency HRV was 57.9 +/- 31.6(NU), increasing to 69.5 +/- 21.3(NU) on Day 3 (p.m.). Tilt-induced increases in heart rate were greater following starvation (10.5 +/- 7.8 vs. 16.1 +/- 8.6 beats min(-1)), and tilt induced decreases in high frequency HRV were greater following starvation (-4.1 +/- 27.7 vs. -28.0 +/- 20.8(NU)). Supine V'CO(2) remained unchanged, whereas V'O(2) increased and respiratory exchange ratio decreased (0.91 +/- 0.10 vs. 0.80 +/- 0.05). Greater vagal withdrawal and elevated heart rate induced by head-up tilting during starvation may indicate increased autonomic sensitivity. PMID- 22038146 TI - Incline plyometrics-induced improvement of jumping performance. AB - The aim of this study was to examine the effects of incline plyometrics training on muscle activation and architecture during vertical jumping and maximum strength. Twenty male participants were divided in two training groups which followed after a 4 week training program. The incline plyometrics group (n = 10) trained by performing consecutive jumps on an inclined surface (15 degrees ) while the plane plyometrics (PP) group (n = 10) performed the same jumps on a plane surface. Both groups trained four times per week and performed 8 sets of 10 jumps in each session. Subjects performed squat jumps, counter movement jumps and drop jumps (DJ) prior to and immediately after the training period, while the electromyographic activity of the medial gastrocnemius (MGAS) and tibialis anterior muscles and the architecture of MGAS were recorded. Maximal isokinetic and isometric strength of the plantar flexors were performed. Analysis of variance showed that only the IP group improved fast DJ height performance by 17.4 and 14.4% (20 and 40 cm, p < 0.05). This was accompanied by a significantly higher MGAS activity during the propulsion phase (24% from 20 cm and 50% from 40 cm, p < 0.05) of the DJ and a longer working fascicle length (5.08%, p < 0.05) compared with the PP group. There were no significant changes in isokinetic and isometric strength of the plantar flexors after training for both groups. The increase of jumping performance, after incline plyometrics should be taken into consideration by coaches, when they apply hopping exercise to improve explosiveness of the plantar flexors. PMID- 22038147 TI - Cycling exercise-induced myofiber transitions in skeletal muscle depend on basal fiber type distribution. AB - The link between specific changes in myofiber type proportions and modulation of training in human skeletal muscle has yet to be unraveled. We investigated whether a defined increase in training volume induces a corresponding change of myofiber shifting in human skeletal muscle with distinct basal myofiber distribution. Twenty-one male cyclists (Age 26 +/- 4 years) with different performance levels were exposed to increased cycling training volume with reduced power output for 3 months. Biopsies were taken from vastus lateralis muscle PRE POST and the proportions of type I, IIa, IIx and IIc myofibers were determined. Total training time did not correlate to the degree of fiber type shifting of any type. In the entire sample of subjects, the proportion of type I myofibers tended to increase (P = 0.14) while IIa fibers decreased significantly (P < 0.05). Subgroups of subjects possessing higher (HPS) and lower proportions (LPS) of type I myofibers at baseline showed a distinct pattern in changing myofiber distribution. Subjects in HPS offered no change in myofiber proportions of any type. In contrast, subjects in LPS showed marked increases in type I (P = 0.06) and a significant reduction in IIa myofibers (P = 0.01). An inverse correlation between baseline proportion of type I and IIa myofibers and its change was observed. We conclude that individual myofiber composition constitutes a modulating factor for exercise-induced changes in its distribution. This might be influenced by altered demands of myofiber recruitment in relation to the intensity of muscle contraction but also by its relative abundance in contracting muscle. PMID- 22038148 TI - Vascular inflammation and blood pressure response to acute exercise. AB - Exaggerated blood pressure (BP) response to exercise is a strong predictor of cardiovascular disease, although the mechanisms remain unknown. The purpose was to examine the association between systemic markers of vascular inflammation and exercise blood pressure (BP) responses. Participants were 191 healthy men and women (aged 45-59 years). Blood pressure was measured at baseline and during 8 min of steady state cycling ergometry exercise (at 50 W). Markers of vascular inflammation (fibrinogen, von Willebrand factor antigen, tumour necrosis factor alpha, interleukin-6 [IL-6], C-reactive protein [CRP]) were measured at baseline together with other traditional risk factors including central adiposity, smoking, alcohol, and habitual physical activity. CRP (beta = 0.30, p < 0.001), IL-6 (beta = 0.25, p = 0.001), and fibrinogen (beta = 0.14, p = 0.04) were associated with exercise systolic BP. The association with CRP remained significant after adjustment for age, sex, resting BP, and other risk factors. Other independent predictors of exercise BP included resting BP, female gender, waist-hip ratio, lower employment grade, and low physical activity level. In summary, central adiposity and vascular inflammatory processes may underlie exaggerated BP responses to acute exercise. PMID- 22038149 TI - Epileptogenic brain lesions in children: the added-value of combined diffusion imaging and proton MR spectroscopy to the presurgical differential diagnosis. AB - PURPOSE: Focal cortical dysplasia (FCD), dysembryoplastic neuroepithelial tumors (DNTs), and gangliogliomas (GGs) share many clinical features, and the presurgical differential diagnosis of these lesions using conventional magnetic resonance imaging (MRI) is challenging in some cases. The purpose of this work was thus to evaluate the capacity of diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS) to distinguish each lesion from the others. METHODS: Seventeen children (mean age 9.0 +/- 4.7 years), who had been referred for epilepsy associated with a brain tumor and operated, were selected. Preoperative MRI examinations were performed on a 1.5 T system and included anatomical images [T2-weighted, fluid-attenuated inversion recovery (FLAIR) and T1 pre- and post-injection images] as well as DWI and MRS [echo time (TE) = 30 and 135 ms]. Apparent diffusion coefficient (ADC) values were calculated in the lesion and healthy control. MRS relative quantification consisted in normalizing each metabolite by the sum (S) of all metabolites (S(TE=135 ms) = NAA+Cr+Cho; S(TE=30 ms) = NAA+Cr+Cho+Glx+mI). Univariate and multivariate analyses were performed in order to determine which criteria could differentiate the different epileptogenic brain lesions. RESULTS: When taken alone, none of the MRI parameters was able to distinguish each disease from the others. Conventional MRI failed classifying two patients. When adding ADC to the linear discriminant analysis (LDA), one patient was still misclassified. Complete separation of the three groups was possible when combining conventional MRI, diffusion, and MRS either at long or short TE. CONCLUSION: This study shows the added-value of multimodal MRI and MRS in the presurgical diagnosis of epileptogenic brain lesions in children. PMID- 22038150 TI - Recurrent orbitofrontal cholesterol granuloma in pediatric patient: case report and review of the literature. AB - Orbitofrontal cholesterol granuloma is a rare entity which typically involves the lateral part of the supraorbital ridge. It causes progressive expansion and erosion of the inner and outer tables of the frontal bone. We describe a case of recurrent orbitofrontal cholesterol granuloma in a 17-year-old girl. In June 2002 this patient had originally presented to an eye clinic with a small palpable mass in the right superolateral orbit, limitation on upgaze, and progressive proptosis. MRI of the orbit revealed an intraorbital extraconal mass with smooth border, high signal on both T1- and T2-weighted magnetic resonance images. She underwent an anterior orbitotomy via a subbrow incision. The lesion was removed completely, and histopathological examination confirmed a cholesterol granuloma. She remained asymptomatic until her presentation in August 2005. On second admission (3 years later), she complained of a tender palpable mass in the superolateral aspect of the right orbit. Her right eye was 4 mm proptosed and 4 mm inferomedially displaced with limited elevation. The rest of the examination was normal. MRI of the orbit showed a large intraorbital but extraconal mass with smooth border, high signal on both T1- and T2-weighted images without enhancement after gadolinium injection. She underwent complete surgical excision by means of a bicoronal approach. Histopathological diagnosis revealed cholesterol granuloma. No recurrence of the lesion has been observed during the last 6 years following the second operation. PMID- 22038151 TI - A newborn with respiratory distress and hydrocephalus caused by a giant mature teratoma. PMID- 22038152 TI - A new form of herniation: the Chiari V malformation. PMID- 22038153 TI - The measurement of CSF flow through the aqueduct in normal and hydrocephalic children: from where does it come, to where does it go? AB - PURPOSE: Despite 100 years of study, the theories of cerebrospinal fluid (CSF) formation and absorption remain controversial. Measuring CSF flow through the aqueduct using magnetic resonance imaging (MRI) provides a unique insight into the physiology of CSF hydrodynamics. The published data in adults tend to refute rather than support the prevailing theories of CSF flow. There are limited data regarding this metric in children. This paper seeks to measure the aqueduct flow in normal and hydrocephalic children to help formulate a more complete theory of CSF flow. METHODS: Twenty-four children with communicating hydrocephalus aged from 4 months to 16 years underwent MRI flow quantification of the aqueduct measuring the net flow. The patients were compared to 19 controls. RESULTS: The controls revealed two different flow patterns: (1) an infantile pattern characterized by flow directed into the ventricular system and (2) a mature pattern with flow directed out of the ventricles, similar to the published findings in adults. In infants with communicating hydrocephalus, the aqueduct flow changed direction but was of similar magnitude compared with the controls (p = 0.001). In the older hydrocephalic children, the flow was elevated 7-fold, but the direction was unchanged compared to the controls (p = 0.002). CONCLUSIONS: There is an abrupt change in the aqueduct CSF flow pattern at the age of 2 years from an infantile pattern to a mature pattern. These findings together with the findings in hydrocephalic children do not support the current theories of CSF hydrodynamics. A new theory of CSF circulation based on capillary absorption is presented. PMID- 22038154 TI - The importance of MTHFR polymorphisms in pediatric cerebral stroke. PMID- 22038155 TI - Early endoscopy-assisted treatment of multiple-suture craniosynostosis. AB - AIMS: Endoscopy-assisted treatment of craniosynostosis constitutes a novel modality for management of complex craniosynostoses. In this work, the authors aimed to assess the safety and advantages of performing these techniques in patients under 4 months of age. PATIENTS AND METHODS: Our study group comprised patients aged 4 months or younger with multiple-suture craniosynostosis undergoing endoscopy-assisted cranial remodeling. RESULTS: Between March 2007 and June 2011, we treated seven patients with combined affected sutures, five with unclassified nonsyndromic craniosynostosis, one with Muenke's and another with Crouzon's syndromes. One child with a cloverleaf skull had a family history of craniosynostosis. Mean age at diagnosis was 35.3 days (1-90 days). The most frequent combinations of involved sutures were sagittal and bicoronal suture (n = 3) and bilateral coronal suture (n = 3). Mean age at treatment was 62.8 days (13 109 days). Blood transfusion was required in only two patients. The mean length of hospital stay was 2.3 days (2-4 days). Mean follow-up period was 20.14 months (7-46 months). No patient presented ventriculomegaly or Chiari I malformation in follow-up studies, and only one showed a vertical disposition of the posterior fossa. No patient presented complications related to the procedures. A good result (Barlett I) was observed at 3- and 6-month follow-up visits. Four patients followed up for more than 1 year did not develop craniolacunae. CONCLUSION: Endoscopy-assisted surgery for correction of craniosynostosis in children under 4 months represents a valid and safe management option. Early treatment may contribute to prevent the development of associated ventriculomegaly and Chiari I malformation. PMID- 22038156 TI - A sustainable byproduct catalyzed domino strategy: facile synthesis of alpha formyloxy and acetoxy ketones via iodination/nucleophilic substitution/hydrolyzation/oxidation sequences. AB - The sustainable byproduct catalyzed domino strategy has been performed for the facile synthesis of alpha-formyloxy and acetoxy ketones via iodination/nucleophilic substitution/hydrolyzation/oxidation sequences from simple and readily available aromatic ketones/unsaturated methyl ketones. PMID- 22038157 TI - Trace amine associated receptor 1 signaling in activated lymphocytes. AB - Although most research to date on Trace Amine Associated Receptor 1 (TAAR1) has focused on its role in the brain, it has been recognized since its discovery in 2001 that TAAR1 mRNA is expressed in peripheral tissues as well, suggesting that this receptor may play a role in non-neurological pathways. This study reports TAAR1 expression, signaling and functionality in rhesus monkey lymphocytes. We detected a high level of TAAR1 protein in immortalized rhesus monkey B cell lines and a significant upregulation of TAAR1 protein expression in rhesus monkey lymphocytes following PHA treatment. Through screening a wide range of signaling pathways for their upregulation following TAAR1 activation by its potent agonist methamphetamine, we identified two transcription factors, CREB and NFAT, which are commonly associated with immune activation. Furthermore, we observed a TAAR1 dependent phosphorylation of PKA and PKC following treatment with methamphetamine in transfected HEK293 cells, immortalized rhesus monkey B cells and PHA-activated rhesus monkey lymphocytes. Accordingly, the high levels of TAAR1 that we observed on lymphocytes are inducible and fully functional, capable of transmitting a signal likely via PKA and PKC activation following ligand binding. More importantly, an increase in TAAR1 receptor expression is concomitant with lymphocyte immune activation, suggesting a possible role for TAAR1 in the generation or regulation of an immune response. TAAR1 is emerging as a potential therapeutic target, with regard to its ability to modulate brain monoamines. The current data raises the possibility that TAAR1-targeted drugs may also alter immune function. PMID- 22038159 TI - Evaluation of CXCL10 as a novel serum marker for predicting liver metastasis and prognosis in colorectal cancer. AB - The aim of this study was to identify novel and reliable serum markers related to the prognosis of colorectal cancer (CRC) patients and to assess the association between selected markers and clinical outcome. We performed experiments using cytokine arrays to investigate the cytokine profiles in serum from stage IV CRC patients, compared with those of stage I patients. Serum CXCL10 was measured using an ELISA in 218 CRC patients and 17 normal volunteers to clarify the association of CXCL10 with clinical outcome. The mean serum CXCL10 concentration in CRC patients was significantly higher compared to that in normal volunteers. Serum CXCL10 levels increased significantly in accordance with the progression of UICC stage classification. Serum CXCL10 was significantly associated with high pathological T stage, the presence of vascular invasion and distant metastasis. Elevated serum CXCL10 levels were significantly associated with poor survival in all stages or in stage I-III with curative patients, respectively, and were an independent marker in predicting liver metastasis. Immunohistochemical analysis showed that CXCL10 was expressed in cancer cells at primary tumor and liver metastases sites, and in normal liver tissue surrounding metastatic cancer cells. Comprehensive analysis using cytokine arrays identified the novel serum prognosis marker CXCL10. Preoperative high serum levels of CXCL10 were associated with poor prognosis and liver metastasis in CRC. PMID- 22038158 TI - [(11)C]DAC-PET for noninvasively monitoring neuroinflammation and immunosuppressive therapy efficacy in rat experimental autoimmune encephalomyelitis model. AB - Neuroimaging measures have potential for monitoring neuroinflammation to guide treatment before the occurrence of significant functional impairment or irreversible neuronal damage in multiple sclerosis (MS). N-Benzyl-N-methyl-2-(7 [(11)C]methyl-8-oxo-2-phenyl-7,8-dihydro-9H-purin-9-yl) acetamide ([(11)C]DAC), a new developed positron emission tomography (PET) probe for translocator protein 18 kDa (TSPO), has been adopted to evaluate the neuroinflammation and treatment effects of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. [(11)C]DAC-PET enabled visualization of neuroinflammation lesion of EAE by tracing TSPO expression in the spinal cords; the maximal uptake value reached in day 11 and 20 EAE rats with profound inflammatory cell infiltration compared with control, day 0 and 60 EAE rats. Biodistribution studies and in vitro autoradiography confirmed these in vivo imaging results. Doubling immunohistochemical studies showed the infiltration and expansion of CD4+ T cells and CD11b+ microglia; CD68+ macrophages were responsible for the increased TSPO levels visualized by [(11)C]DAC-PET. Furthermore, mRNA level analysis of the cytokines by quantitative reverse-transcription polymerase chain reaction (qRT PCR) revealed that TSPO+/CD4 T cells, TSPO+ microglia and TSPO+ macrophages in EAE spinal cords were activated and secreted multiple proinflammation cytokines to mediate inflammation lesions of EAE. EAE rats treated with an immunosuppressive agent: 2-amino-2-[2-(4-octylphenyl)ethyl] propane-1,3 diolhydrochloride (FTY720), which exhibited an absence of inflammatory cell infiltrates, displaying a faint radioactive signal compared with the high accumulation of untreated EAE rats. These results indicated that [(11)C] DAC-PET imaging is a sensitive tool for noninvasively monitoring the neuroinflammation response and evaluating therapeutic interventions in EAE. PMID- 22038160 TI - Single-port-access, hand-assisted laparoscopic surgery for benign large adnexal tumors versus single-port pure laparoscopic surgery for adnexal tumors. AB - BACKGROUND: Single-port-access hand-assisted laparoscopic surgery (SPA-HALS) is a method intended to provide surgical outcomes with advantages similar to those of SPA-pure laparoscopic surgery (SPA-PLS) for patients with benign large adnexal tumors and to reduce the spillage of tumor contents. This study aimed to assess the feasibility and methodology of SPA-HALS for benign large adnexal tumors and to compare the surgical outcomes of SPA-HALS and SPA-PLS performed by a single surgeon (H.-J. R.). METHODS: Between March 2009 and February 2011, 139 patients underwent SPA adnexal surgery. The SPA-PLS procedure was performed for 96 candidates for conventional laparoscopic adnexal surgery, whereas SPA-HALS was performed for 43 patients with large adnexal tumors. The patient demographics and surgical outcomes of these two groups were compared. RESULTS: The median adnexal tumor size was larger in the patients who underwent SPA-HALS than in those who underwent SPA-PLS (10.9 vs. 6.3 cm; p < 0.001). Spillage occurred for four patients in the SPA-HALS group (10.3%) compared with 33 patients in the SPA-PLS group (31.3%) (p = 0.005). The relative risk of spillage was 4.43 times higher in the SPA-PLS than in the SPA-HALS group (95% confidence interval [CI], 1.45 13.53). Adnexa-conserving surgery was significantly more frequent in the SPA-HALS group than in the SPA-PLS group (76.7% vs. 43.8%; p < 0.001). Additional procedures were less frequent in the SPA-HALS group (16.3% vs. 33.3%, p = 0.043). The median estimated blood loss was significantly lower in the SPA-HALS group (50 vs. 105 ml; p = 0.001). The two groups did not differ significantly in median operation time (75 vs. 70 min), complication rate (0% vs. 3.1%), or postoperative hospital stay (2 vs. 2 days). CONCLUSION: The findings showed that SPA-HALS extracorporeal adnexal surgery allows for thorough evaluation of peritoneal structure and complete surgery of benign large adnexal tumors while retaining the advantages of SPA adnexal surgery. Furthermore, this technique may reduce the intraperitoneal spillage rate for benign large adnexal tumors. PMID- 22038161 TI - Using National Surgical Quality Improvement Program (NSQIP) data for risk adjustment to compare Clavien 4 and 5 complications in open and laparoscopic colectomy. AB - BACKGROUND: Laparoscopic colectomy has been associated with fewer postoperative complications than open colectomy. However, it is unclear whether this is true for the most severe complications typically requiring treatment in an intensive care unit (ICU). The authors hypothesized that laparoscopic colectomy patients have fewer of the most severe complications even after adjustment for comorbidity risk. METHODS: Using the National Surgical Quality Improvement Program (NSQIP) public use files for 2005-2008, the authors identified all laparoscopic (n = 12,455) and open (n = 33,190) colectomies by current procedural terminology (CPT) code. Using the Clavien classification for postoperative complications, they identified NSQIP data points most consistent with Clavien grade 4 complications requiring ICU care (postoperative septic shock, postoperative dialysis, pulmonary embolism, myocardial infarction, cardiac arrest, prolonged ventilatory requirements, need for reintubation) or grade 5 complication (mortality). Statistical analysis was performed using SPSS software. Odds ratios were calculated to compare laparoscopic and open colectomy regarding the probability of having any Clavien class 4 or 5 complication. Logistic regression was performed to account for the effect of preoperative conditions (American Society of Anesthesiology class, wound class, gender, preoperative functional status, preoperative albumin level, azotemia, thrombocytopenia, emergency case, and age >70 years) on complications. RESULTS: The univariate odds ratio showed a 2.27- to 5.52-fold greater likelihood that a patient would have a complication requiring ICU admission if open rather than laparoscopic surgery was performed (p < 0.001). Multivariate logistic regression accounting for preoperative comorbidities that might affect outcome showed persistence of an increase in complications, with an odds ratio range of 1.63 to 2.21. CONCLUSION: Evaluation of the NSQIP database demonstrated that laparoscopic colectomy confers an independent protective effect on the frequency of ICU-level (Clavien grade 4) complications and mortality. The protective effect remained evident after correction for preoperative conditions that might have affected outcome. PMID- 22038162 TI - Minimally invasive video-assisted thyroidectomy: an analysis of results and a revision of indications. AB - BACKGROUND: The first report of minimally invasive video-assisted thyroidectomy (MIVAT) was published in 1999, and the indications were progressively implemented: from cytologically undetermined thyroid nodules to intermediate-risk differentiated thyroid cancers. The aim of this study was to review the entire series of patients who underwent a MIVAT, critically analyzing its indications and contraindications and trying to figure out how the indications might be extended. METHODS: From 1998 to 2009, a total of 1,946 patients (1,659 females, 287 males; mean age = 40.2 years) underwent MIVAT in our department. Inclusion criteria were benign thyroid nodules <35 mm, malignant nodules <20 mm, and an ultrasonographically estimated thyroid volume (ETV) <25 cc. The presence of suspicious or metastatic lymph nodes and the presence of severe thyroiditis were considered a contraindication for MIVAT. RESULTS: A total thyroidectomy was performed in 1,435 patients (72.3%). A total lobectomy was performed in 511 cases (26.3%), and a central neck node sampling was associated with total thyroidectomy in 104 cases. Final histology revealed benign disease in 979 cases (51.5%) and a malignancy was diagnosed in 915 cases (48.5%). Unexpected thyroiditis was found on final histology in 17.9% of the patients with benign disease and 30.9% of patients with malignancy. The incidence of thyroiditis was significantly different in these two populations (p < 0.0001). CONCLUSION: Our data confirm the validity of the traditional indications for MIVAT: low-risk differentiated thyroid cancer (DTC), cytologically undetermined nodules, and small-volume benign thyroid disease. The indications may be further and safely extended to those patients with associated thyroiditis and those with intermediate-risk DTC. MIVAT can be proposed on a much larger scale than it was at its onset and cannot be considered an option for only a limited number of patients. PMID- 22038163 TI - CO2 pneumoperitoneum impact on early liver and lung cytokine expression in a rat model of abdominal sepsis. AB - BACKGROUND: Experimental evidence suggests that laparoscopy could have reduced inflammatory sequelae compared with laparotomy following abdominal surgery for peritonitis. The aim of the present study is to investigate the possible beneficial effects of CO(2) insufflation on liver and lung expression of proinflammatory cytokines during sepsis. METHODS: Cecal ligation and puncture (CLP) was induced in Sprague-Dawley rats, and 6 h later rats were randomly subjected to CO(2) pneumoperitoneum (5-7 mmHg) or to laparotomy for 1 h. At the end of the CO(2) pneumoperitoneum or laparotomy procedures, animals were sacrificed, and liver and lung were removed and stored for molecular and histological analysis. RESULTS: Liver and lung expression of proinflammatory cytokines was significantly reduced in animals subjected to CO(2) pneumoperitoneum compared with laparotomy. In particular, tumor necrosis factor alpha (TNF-alpha) protein expression was significantly reduced (p < 0.05) following CO(2) pneumoperitoneum compared with laparotomy procedures. Interleukin (IL)-6 protein expression was accordingly, markedly reduced (p < 0.05) following CO(2) pneumoperitoneum. Histological analysis showed a reduced inflammatory infiltrate in liver and lung from animals subjected to CO(2) pneumoperitoneum compared with laparotomy. CONCLUSIONS: Our results support the hypothesis that laparoscopic procedures reduce the inflammatory cascade, following peritoneal sepsis, via reduced expression of proinflammatory cytokines. PMID- 22038164 TI - Resection and radiofrequency ablation in the treatment of hepatocellular carcinoma: a single-center experience. AB - BACKGROUND: We have been utilizing both resection and laparoscopic radiofrequency ablation (RFA) to treat hepatocellular carcinoma (HCC). The aim of this study is to describe patient characteristics and outcome for each treatment modality from a single institution. METHODS: Medical records of HCC patients who underwent resection (n = 92) or laparoscopic (RFA) (n = 92) between 1997 and 2010 were reviewed. Univariate Kaplan-Meier and multivariate Cox proportional-hazards model were used to analyze survival. RESULTS: Patients with normal liver function and larger tumors were resected, and those with liver dysfunction, portal hypertension, and multiple tumors were ablated. Tumor size was larger in the Resection group, whereas number of tumors was higher in the RFA group. Child class and Barcelona Clinic Liver Cancer (BCLC) staging were more advanced in the RFA group. Hospital stay was longer, and morbidity and mortality higher in the Resection versus the RFA group. There was no difference in disease-free survival, but the 5-year actual survival was significantly higher (40% versus 21%) in the Resection group. On univariate analysis, number of tumors, tumor size, platelet count, BCLC stage, Child class, and type of surgery were predictors of overall survival. On multivariate analysis, Child class and number of tumors were independent predictors of overall survival. CONCLUSIONS: To our knowledge, this is the largest North American series reporting on RFA and resection for HCC from a single institution. Herein, we describe the perioperative and oncologic outcomes to be expected when these modalities are used in a certain treatment algorithm. PMID- 22038165 TI - Laparoscopic rectal resection for severe endometriosis of the mid and low rectum: technique and operative results. AB - BACKGROUND: Although several studies have shown that laparoscopic resection is safe and feasible in bowel endometriosis, limited data are available on the specific treatment for endometriosis of the rectum. The aim of this study is to describe operative and postoperative outcomes after laparoscopic resection of the mid/low rectum for endometriosis. METHODS: Between 2002 and 2010, 750 patients (median age 33 years) underwent laparoscopic resection of the mid/low rectum for deep infiltrating endometriosis at a single institution. All operations were performed with a standardized technique by a single surgeon. RESULTS: Median operative time was 255 min, and median blood loss 150 ml. Of patients, 7% required blood transfusions. Laparotomic conversion rate was 1.6%. Mechanical low and very low colorectal anastomoses were carried out in 92.5 and 7.5% of patients, respectively. Temporary ileostomy rate was 14.5%. Median length of stay was 8 days. Overall surgical morbidity was 9% with no mortality. Rates of anastomotic leak, rectovaginal fistula, and intraabdominal bleeding were 3, 2, and 1.2%. Forty patients (5.5%) required reoperation. CONCLUSIONS: Laparoscopic resection of the mid/low rectum for endometriosis can be performed safely with acceptable rates of morbidity/reoperation and with low rates of specific complications, including anastomotic leak and rectovaginal fistula. The very high surgical volume of the operating surgeon is probably one of the most important factors in order to maximize postoperative outcomes. PMID- 22038166 TI - The enhanced view-totally extraperitoneal technique for repair of inguinal hernia. AB - BACKGROUND: The totally extraperitoneal (TEP) approach for repair of inguinal hernia is the preferred technique since it does not penetrate the peritoneal cavity, thus avoiding potential intraperitoneal complications. The TEP technique allows for regional or even local plus sedative anesthesia, and it gives us an incomparable view of the inguinal region and hernias exactly where they originate. Part of the difficulty with the TEP technique is the limited space it provides for dissection. METHODS: We describe a modification of the classical TEP approach which overcomes this limitation: the e-TEP technique. Since October 2010 we have performed 36 e-TEP procedures. Many of these were in difficult cases such as inguinoscrotal and incarcerated hernias and patients with previous radical prostatectomy. We present an initial evaluation of this group of patients. RESULTS: Results in terms of pain and time off work were the same as with the classical technique. The average operating time was 38 min. This is longer than usual, probably due to the complexity of the cases performed and the time spent in documenting the technique for educational purposes. The peritoneum was often accidentally opened and air leaked into the peritoneal cavity without interfering with the completion of the surgery. We had two small seromas and one case of skin sloughing at the umbilical wound in a case of umbilical and bilateral inguinal hernias. We have had no recurrences, but follow-up has been short. CONCLUSIONS: Our initial experience with the e-TEP technique has been satisfactory. We have had no conversions in spite of the difficult cases selected. There were no major complications, and functional results were excellent. We believe this modification has a place in the armamentarium for hernia repair. PMID- 22038167 TI - How does the robot affect outcomes? A retrospective review of open, laparoscopic, and robotic Heller myotomy for achalasia. AB - BACKGROUND: Robotic techniques are routinely used in urological and gynecological procedures; however, their role in general surgical procedures is limited. A robotic technique has been successfully adopted for a minimally invasive Heller myotomy procedure for achalasia. This study aims to compare perioperative outcomes following open, laparoscopic, and robotic Heller myotomy. METHODS: This study is a multicenter, retrospective analysis utilizing a large administrative database. The University Health System Consortium (UHC) is an alliance between academic medical centers and affiliate hospitals. The UHC database was accessed using International Classification of Diseases, Ninth Revision, Clinical Modification codes and analyzed. RESULTS: 2,683 patients with achalasia underwent Heller myotomy between October 2007 and June 2011. Myotomy was performed by open surgery (OM) in 418 patients, by laparoscopic approach (LM) in 2,116, and by robotic approach (RM) in 149. Comparison between LM and RM groups demonstrated no significant difference in mortality (0.14 vs. 0.0%; P = 1), morbidity (5.19 vs. 4.02%; P = 0.7), intensive care unit (ICU) admission (6.62 vs. 3.36%; P = 0.12), length of stay (LOS) (2.70 +/- 3.87 days vs. 2.42 +/- 2.69 days; P = 0.34), or 30 day readmission (1.41 vs. 2.84%; P = 0.27). However, hospital costs were significantly lower for the LM group (US $7,441 +/- 7,897 vs. US $9,415 +/- 5,515; P = 0.0028). Comparison between OM and RM demonstrated significant lower morbidity (9.08 vs. 4.02%; P = 0.02), ICU admission rate (14.01 vs. 3.36%, P = 0.0002), and LOS (4.42 +/- 5.25 days vs. 2.42 +/- 2.69 days; P = 0.0001). CONCLUSIONS: The perioperative outcomes are superior in LM and RM groups when compared with OM. The outcomes for the LM and RM group are comparable, with the robotic group having slightly improved results, although with increased costs. We conclude that robotic surgery is equivalent in safety and efficacy to laparoscopic Heller myotomy, and feel that the increased cost should come down as surgeons and manufacturers work together on cost reduction strategies. PMID- 22038168 TI - Should SAGES advance minimally invasive surgery in space? PMID- 22038169 TI - Adult esophagogastric junction distensibility during general anesthesia assessed with an endoscopic functional luminal imaging probe (EndoFLIP(r)). AB - BACKGROUND: Increased esophagogastric junction distensibility occurs with esophageal reflux. The EndoFLIP((r)) is now available as a clinical tool to measure this. Control data for patients without reflux has to date only been available for a handful of patients evaluated under sedation during endoscopy. This study explores the baseline data for patients who undergo laparoscopy using general anesthesia with pneumoperitoneum. METHODS: Patients who require surgery in the absence of a history of esophageal reflux underwent EndoFLIP((r)) evaluation of pressure, cross-sectional area, and distensibility with bag fills of 30 and 40 ml. This was performed after induction of anesthesia, during pneumoperitoneum, and just before extubation. RESULTS: Baseline levels were established and were noted to be significantly affected by the impact of pneumoperitoneum, with negligible effects from general anesthesia, patient gender, age, body mass index, or muscle relaxation. CONCLUSIONS: These data provide a guide for more accurate intraoperative EndoFLIP((r)) calibration of crural hiatal repair during surgery. PMID- 22038170 TI - Induction of primitive pigment cell differentiation by visible light (helium-neon laser): a photoacceptor-specific response not replicable by UVB irradiation. AB - Solar lights encompass ultraviolet (UV), visible, and infrared spectrum. Most previous studies focused on the harmful UV effects, and the biologic effects of lights at other spectrums remained unclear. Recently, lights at visible region have been used for regenerative purposes. Using the process of vitiligo repigmentation as a research model, we focused on elucidating the pro differentiation effects induced by visible light. We first showed that helium neon (He-Ne) laser (632.8 nm) irradiation stimulated differentiation of primitive pigment cells, an effect not replicable by UVB treatment even at high and damaging doses. In addition, significant increases of mitochondrial DNA copy number and the regulatory genes for mitochondrial biogenesis were induced by He Ne laser irradiation. Mechanistically, we demonstrated that He-Ne laser initiated mitochondrial retrograde signaling via a Ca(2+)-dependent cascade. The impact on cytochrome c oxidase within the mitochondria is responsible for the efficacy of He-Ne laser in promoting melanoblast differentiation. Taken together, we propose that visible lights from the sun provide important environmental cues for the relatively quiescent stem or primitive cells to differentiate. In addition, our results also indicate that visible light may be used for regenerative medical purposes involving stem cells. PMID- 22038171 TI - A novel hybrid promoter responsive to pathophysiological and pharmacological regulation. AB - The aim of this study was to construct a promoter containing DNA motifs for an endogenous transcription factor associated with inflammation along with motifs for pharmacological regulation factors. We demonstrate in transfected cells that expression of a gene of interest is induced by hypoxic conditions or through pharmacological induction, and also show pharmacological repression. In vivo studies utilised electroporation of plasmid to mouse paws, a delivery method shown to be effective by bioluminescence imaging. For gene therapy, the promoter was used to drive expression of IL-1Ra in a paw inflammation model with therapeutic effect observed which was further enhanced when the promoter was additionally induced with a pharmacological activator. One of the most important observations from this study was that promoter induction by hypoxia or inflammation could be prevented by the pharmacological repressor in the absence of doxycycline. These studies demonstrate that hybrid promoters enable pharmacological adjustment to the pathophysiological level of gene expression and, importantly, that they allow termination of gene expression even in the presence of pathophysiological stimuli. PMID- 22038172 TI - Does lateral release change patellofemoral forces and pressures?: a pilot study. AB - BACKGROUND: One complication of TKA is postoperative anterior knee pain. Balancing retinacular tissue tension to improve patellar tracking is essential in preventing pain. Lateral release might help balance tension although the quantitative changes in patellofemoral force and pressure differentials after lateral release are unknown. QUESTIONS/PURPOSES: We asked if there are differences in patellofemoral forces and pressures for knees resurfaced with standard and gender-specific components and whether lateral release changes these differentials. METHODS: We studied six fresh-frozen cadaver knees with native knees and knees that had TKAs with patellofemoral resurfacing using traditional and gender-specific components. The knees were taken through passive ROM, and the means for medial and lateral peak pressure and maximum force were calculated before and after a lateral release was performed. RESULTS: In traditional resurfaced knees, lateral peak pressure was greater than medial peak pressure by 727.6 +/- 550.0 kPa and lateral maximum force was greater than medial maximum force by 29.6 +/- 15.9 N. Lateral release decreased the pressure (71.4 +/- 826.0 kPa) and force (10.0 +/- 32.1 N) differentials in the traditional but not in the gender-specific design. In gender-specific resurfaced knees, lateral peak pressure was greater than medial peak pressure by 158.7 +/- 360.0 kPa and lateral maximum force was greater than medial maximum force by 15.5 +/- 10.4 N. Lateral release increased the pressure (285.7 +/- 565.0 kPa) and force (16.8 +/- 10.8 N) differentials. CONCLUSIONS: Our preliminary data suggest lateral release is more effective in reducing peak pressure and maximum force differentials in knees resurfaced with traditional standard components than with gender-specific components. CLINICAL RELEVANCE: The lateral release technique might help with tissue balancing when using standard components in TKA. PMID- 22038173 TI - Unicompartmental versus total knee arthroplasty database analysis: is there a winner? AB - BACKGROUND: TKA and unicompartmental knee arthroplasty (UKA) are both utilized to treat unicompartmental knee arthrosis. While some surgeons assume UKA provides better function than TKA, this assumption is based on greater final outcome scores rather than on change in scores and many patients with UKA have higher preoperative scores. QUESTIONS/PURPOSES: We therefore asked whether TKA would demonstrate (1) better change in clinical outcome scores from preoperative to postoperative states and (2) better survivorship than UKA. METHODS: We evaluated 4087 patients with 5606 TKAs and 179 patients with 279 UKAs performed between 1978 and 2009. Patients with TKA were older and heavier than patients with UKA (mean age, 68 versus 66 years; mean BMI, 32 versus 29). We compared preoperative, latest postoperative, and change in Knee Society Clinical Rating System (KSCRS), SF-12, and WOMAC scores. Minimum followup was 2 years (UKA: mean, 7 years; range, 2.0-23 years; TKA: mean, 6.5 years; range, 2.0-33 years). Preoperative outcome measure scores (WOMAC, SF-12, KSCRS) were higher in the UKA group. RESULTS: Patients with UKA had higher postoperative KSCRS and SF-12 mental scores. Changes in score for all WOMAC domains were similar between groups. Total KSCRS changes in score were similar between groups, although patients with TKA had higher knee scores (49 versus 43) but lower function scores than UKA (21 versus 26). Cumulative revision rate was higher for UKA than for TKA (13% versus 7%). Kaplan Meier survivorship at 5 and 10 years was 95% and 90%, respectively, for UKA and 98% and 95%, respectively, for TKA. CONCLUSIONS: While patients with UKA had higher pre- and postoperative scores than patients with TKA, the changes in scores were similar in both groups and survival appeared higher in patients with TKA. PMID- 22038174 TI - The Frank Stinchfield Award: Dislocation in revision THA: do large heads (36 and 40 mm) result in reduced dislocation rates in a randomized clinical trial? AB - BACKGROUND: Dislocation after revision THA is a common complication. Large heads have the potential to decrease dislocation rate, but it is unclear whether they do so in revision THA. QUESTIONS/PURPOSES: We therefore determined whether a large femoral head (36 and 40 mm) resulted in a decreased dislocation rate compared to a standard head (32 mm). METHODS: We randomized 184 patients undergoing revision THA to receive either a 32-mm head (92 patients) or 36- and 40-mm head (92 patients) and stratified patients by surgeon. The two groups had similar baseline demographics. The primary end point was dislocation. Quality-of life (QOL) measures were WOMAC and SF-36. The mean followup for dislocation was 5 years (range, 2-7 years); the mean followup for QOL was 2.2 years (range, 1.6-4 years). RESULTS: In the 36- and 40-mm head group, the dislocation rate was 1.1% (one of 92) versus 8.7% (eight of 92) for the 32-mm head. There was no difference in QOL outcomes between the two groups. CONCLUSIONS: Our observations confirm a large femoral head (36 or 40 mm) reduces dislocation rates in patients undergoing revision THA at short-term followup. We now routinely use large heads with a highly crosslinked polyethylene acetabular liner in all revision THAs. LEVEL OF EVIDENCE: Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22038175 TI - MHC class II genes in the European badger (Meles meles): characterization, patterns of variation, and transcription analysis. AB - The major histocompatibility complex (MHC) comprises many genes, some of which are polymorphic with numerous alleles. Sequence variation among alleles is most pronounced in exon 2 of the class II genes, which encodes the alpha1 and beta1 domains that form the antigen-binding site (ABS) for the presentation of peptides. The MHC thus plays an important role in pathogen defense. European badgers (Meles meles) are a good species in which to study the MHC, as they harbor a variety of pathogens. We present the first characterization of MHC class II genes, isolated from genomic DNA (gDNA) and complementary DNA (cDNA), in the European badger. Examination of seven individuals revealed four DRB, two DQB, two DQA, and two DRA putatively functional gDNA sequences. All of these sequences, except DRA, exhibited high variability in exon 2; DRB had the highest variability. The ABS codons demonstrated high variability, due potentially to balancing selection, while non-ABS codons had lower variability. Positively selected sites were detected in DRB and DQA. Phylogenetic analysis demonstrated trans-species polymorphism of class II genes. Comparison with cDNA from whole blood revealed that only DRB had a transcription pattern reflecting the alleles that were present in the gDNA, while the other three genes had disparities between gDNA and cDNA. Only one sequence was transcribed, even though two gDNA sequences were present, from each of both DQB and DRA. Our characterization of badger MHC sequences forms a basis for further studies of MHC variability, mate choice, and pathogen resistance in this, and other, species. PMID- 22038176 TI - In memoriam. Donald Wayne Bailey 1926-2010. PMID- 22038177 TI - A call to arms for systematists: revitalising the purpose and practises underpinning the description of novel microbial taxa. AB - Prokaryotic systematics is a fundamentally important discipline that provides a framework for the activities of all microbiologists. Here we propose that the field has become mired in a sea of perceived rules and regulations, many of which stipulate what is considered 'sufficient' for the phenotypic characterisation of novel prokaryotic taxa. Importantly, we argue also that the principles and practise of prokaryotic systematics have not yet fully embraced the revolution in biological understanding that has occurred through the availability of huge numbers of whole genome sequences. We therefore propose that a significant reappraisal of the procedures used to describe novel prokaryotic taxa is needed, including the likely introduction of new publication formats. Urgent action is needed to revitalise the practise of prokaryotic systematics in order to maintain this discipline as an attractive career choice for twenty first century life scientists. PMID- 22038178 TI - Role of conserved active site tryptophan-101 in functional activity and stability of phosphoserine aminotransferase from an enteric human parasite. AB - Site-directed mutagenesis study was performed to elucidate the role of conserved tryptophan-101 present at the active site of phosphoserine aminotransferase from an enteric human parasite Entamoeba histolytica. Fluorescence resonance energy transfer and molecular dynamic simulation show that the indole ring of Trp101 stacks with the cofactor PLP. Loss of enzymatic activity and PLP polarization values suggest that Trp101 plays a major role in maintaining a defined PLP microenvironment essentially required for optimal enzymatic activity. Studies on W101F, W101H and W101A mutants show that only the indole ring of the conserved Trp101 forms most favorable stacking interaction with the pyridine ring of the cofactor PLP. Protein stability was compromised on substitution of Trp101 with Phe/His/Ala amino acids. A difference in conformational free energy of 1.65 kcal mol(-1) was observed between WT-protein and W101A mutant. PMID- 22038179 TI - Design, synthesis and biological activity of new neurohypophyseal hormones analogues conformationally restricted in the N-terminal part of the molecule. Highly potent OT receptor antagonists. AB - In this study we present the synthesis and some pharmacological properties of fourteen new analogues of neurohypophyseal hormones conformationally restricted in the N-terminal part of the molecule. All new peptides were substituted at position 2 with cis-1-amino-4-phenylcyclohexane-1-carboxylic acid (cis-Apc). Moreover, one of the new analogues: [cis-Apc(2), Val(4)]AVP was also prepared in N-acylated forms with various bulky acyl groups. All the peptides were tested for pressor, antidiuretic, and in vitro uterotonic activities. We also determined the binding affinity of the selected compounds to human OT receptor. Our results showed that introduction of cis -Apc(2) in position 2 of either AVP or OT resulted in analogues with high antioxytocin potency. Two of the new compounds, [Mpa(1),cis-Apc(2)]AVP and [Mpa(1),cis-Apc(2),Val(4)]AVP, were exceptionally potent antiuterotonic agents (pA(2) = 8.46 and 8.40, respectively) and exhibited higher affinities for the human OT receptor than Atosiban (K (i) values 5.4 and 9.1 nM). Moreover, we have demonstrated for the first time that N -terminal acylation of AVP analogue can improve its selectivity. Using this approach, we obtained compound Aba[cis-Apc(2),Val(4)]AVP (XI) which turned out to be a moderately potent and exceptionally selective OT antagonist (pA(2) = 7.26). PMID- 22038180 TI - Anti-tissue transglutaminase antibodies activate intracellular tissue transglutaminase by modulating cytosolic Ca2+ homeostasis. AB - Anti-tissue transglutaminase (tTG) antibodies are specifically produced in the small-intestinal mucosa of celiac disease (CD) patients. It is now recognized that these antibodies, acting on cell-surface tTG, may play an active role in CD pathogenesis triggering an intracellular response via the activation of different signal transduction pathways. In this study, we report that anti-tTG antibodies, both commercial and from a CD patient, induce a rapid Ca(2+) mobilization from intracellular stores in Caco-2 cells. We characterized the mechanism of Ca(2+) release using thapsigargin and carbonylcyanide-p-trifluoromethoxyphenylhydrazone, which are able to deplete specifically endoplasmic reticulum and mitochondria of Ca(2+), respectively. Our data highlight that both pathways of calcium release were involved, thus indicating that the spectrum of cellular responses downstream can be very wide. In addition, we demonstrate that the increased Ca(2+) level in the cells evoked by anti-tTG antibodies was sufficient to activate tTG, which is normally present as a latent protein due to the presence of low Ca(2+) and to the inhibitory effect of GTP/GDP. Herein, we discuss the importance of intracellular tTG activation as central in the context of CD pathogenesis. PMID- 22038181 TI - Lasiocepsin, a novel cyclic antimicrobial peptide from the venom of eusocial bee Lasioglossum laticeps (Hymenoptera: Halictidae). AB - In the venom of eusocial bee Lasioglossum laticeps, we identified a novel unique antimicrobial peptide named lasiocepsin consisting of 27 amino acid residues and two disulfide bridges. After identifying its primary structure, we synthesized lasiocepsin by solid-phase peptide synthesis using two different approaches for oxidative folding. The oxidative folding of fully deprotected linear peptide resulted in a mixture of three products differing in the pattern of disulfide bridges. Regioselective disulfide bond formation significantly improved the yield of desired product. The synthetic lasiocepsin possessed antimicrobial activity against both Gram-positive and -negative bacteria, antifungal activity against Candida albicans, and no hemolytic activity against human erythrocytes. We synthesized two lasiocepsin analogs cyclized through one native disulfide bridge in different positions and having the remaining two cysteines substituted by alanines. The analog cyclized through a Cys8-Cys25 disulfide bridge showed reduced antimicrobial activity compared to the native peptide while the second one (Cys17-Cys27) was almost inactive. Linear lasiocepsin having all four cysteine residues substituted by alanines or alkylated was also inactive. That was in contrast to the linear lasiocepsin with all four cysteine residues non paired, which exhibited remarkable antimicrobial activity. The shortening of lasiocepsin by several amino acid residues either from the N- or C-terminal resulted in significant loss of antimicrobial activity. Study of Bacillus subtilis cells treated by lasiocepsin using transmission electron microscopy showed leakage of bacterial content mainly from the holes localized at the ends of the bacterial cells. PMID- 22038182 TI - Heterologous expression and characterization of the hydrophobin HFBI in Pichia pastoris and evaluation of its contribution to the food industry. AB - The class II hydrophobin HFBI from Trichoderma reesei was heterologously expressed by Pichia pastoris using pPIC9 vector under the control of the promoter AOX1. The recombinant HFBI (rHFBI) was purified by ultrafiltration and reverse phase high performance liquid chromatography. Tricine-SDS-PAGE and Western blotting demonstrated that rHFBI with the expected molecular weight of 7.5 kDa was secreted into the culture medium. X-ray photoelectron spectroscopy and water contact angle measurements indicated that rHFBI could lead to the conversion of the wettability of the hydrophobic siliconized glass and hydrophilic mica surfaces relying on the self-assembly membrane on hydrophobic/hydrophilic interfaces. It was demonstrated that rHFBI had the ability to stabilize oil droplets, which was far excess of the class I hydrophobin HGFI heterologously expressed in P. pastoris (rHGFI) and the typical food emulsifier sodium caseinate. In gushing experiments, it was shown that rHFBI was a strong gushing inducer in beer, whereas rHGFI did not display any signs of gushing. This provided the potential of rHFBI to be used as a novel emulsifying agent and a predictor of gushing risk. PMID- 22038183 TI - C3-triiodocyclotriveratrylene as a key intermediate to fluorescent probes: application to selective choline recognition. AB - A new strategy to obtain fluorescent cyclotriveratrylene (CTV) probes is proposed. The key intermediate, a triiodo CTV, is prepared in 3 steps with 47% overall yield. The whole synthesis requires only one purification step. The potential of this triiodo CTV as an intermediate is illustrated through the synthesis of a fluorescent phosphorylated probe that is able to bind choline and acetylcholine in pseudo-physiological conditions, with selectivity towards choline. As a consequence, this intermediate should allow us to rapidly form a library of probes in order to highlight the most promising ones. PMID- 22038184 TI - Oxygen evolution from single- and multiple-turnover light pulses: temporal kinetics of electron transport through PSII in sunflower leaves. AB - Oxygen evolution per single-turnover flash (STF) or multiple-turnover pulse (MTP) was measured with a zirconium O(2) analyzer from sunflower leaves at 22 degrees C. STF were generated by Xe arc lamp, MTP by red LED light of up to 18000 MUmol quanta m(-2) s(-1). Ambient O(2) concentration was 10-30 ppm, STF and MTP were superimposed on far-red background light in order to oxidize plastoquinone (PQ) and randomize S-states. Electron (e(-)) flow was calculated as 4 times O(2) evolution. Q (A) -> Q (B) electron transport was investigated firing double STF with a delay of 0 to 2 ms between the two. Total O(2) evolution per two flashes equaled to that from a single flash when the delay was zero and doubled when the delay exceeded 2 ms. This trend was fitted with two exponentials with time constants of 0.25 and 0.95 ms, equal amplitudes. Illumination with MTP of increasing length resulted in increasing O(2) evolution per pulse, which was differentiated with an aim to find the time course of O(2) evolution with sub millisecond resolution. At the highest pulse intensity of 2.9 photons ms(-1) per PSII, 3 e(-) initially accumulated inside PSII and the catalytic rate of PQ reduction was determined from the throughput rate of the fourth and fifth e(-). A light response curve for the reduction of completely oxidized PQ was a rectangular hyperbola with the initial slope of 1.2 PSII quanta per e(-) and V (m) of 0.6 e(-) ms(-1) per PSII. When PQ was gradually reduced during longer MTP, V (m) decreased proportionally with the fraction of oxidized PQ. It is suggested that the linear kinetics with respect to PQ are apparent, caused by strong product inhibition due to about equal binding constants of PQ and PQH(2) to the Q (B) site. The strong product inhibition is an appropriate mechanism for down regulation of PSII electron transport in accordance with rate of PQH(2) oxidation by cytochrome b(6)f. PMID- 22038185 TI - Comparison of inhibitors of renin-angiotensin-aldosterone system (RAS) and combination therapy of steroids plus RAS inhibitors for patients with advanced immunoglobulin A nephropathy and impaired renal function. AB - BACKGROUND: The adaptation of steroid therapy and the effect of renin-angiotensin aldosterone system inhibitors (RASIs) for advanced immunoglobulin A nephropathy (IgAN) patients with impaired renal function are still controversial. METHODS: We divided 63 IgAN patients with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m(2) and proteinuria >= 0.5 g/day into two groups: the RASI group (RASI, n = 33), treated with RASIs alone; and the combination group (COMBI, n = 30), treated with corticosteroids and RASIs. We analyzed the clinical and histological background, renal survival rate, and the risk factors for progression. RESULTS: Renal function (mean eGFR: COMBI 46.4 vs. RASI 47.0 ml/min/1.73 m(2)), the amount of proteinuria (median: COMBI 1.39 vs. RASI 1.17 g/g creatinine) and histological backgrounds were not significantly different between the groups, but urinary red blood cells (U-RBCs) were significantly higher in the COMBI group than in the RASI group (median: COMBI 30.0 vs. RASI 10.0 counts/high-power field, P = 0.0171). The serial change in proteinuria did not differ until 5 years after treatment, but U-RBCs were significantly decreased in both groups (P < 0.0001), and eGFR was significantly decreased in the RASI group (P < 0.001) but not in the COMBI group. The results for each year after treatment did not differ significantly between both groups. The renal survival rate was not significantly different between the groups. There was no independent risk factor for progression by Cox regression analysis. CONCLUSION: Combination therapy with steroids and RASIs was not superior to monotherapy with RASIs for advanced IgAN with impaired renal function. PMID- 22038186 TI - Cerebral hemorrhage due to internal jugular vein stenosis in a hemodialysis patient. AB - A 53 year old female with ESRD on hemodialysis presented with headache, vomiting, and lethargy that had started 2 h prior to presentation. Magnetic resonance imaging revealed parenchymal hemorrhage in the temporal, occipital, and cerebellar white matter. Magnetic resonance venography disclosed hypoplastic transverse sinus. On cerebral angiogram there was no evidence of cerebral aneurysm, vasculitis or vascular malformation. Angiogram demonstrated a high grade stenosis was present in the left internal jugular vein (IJV) just below the anastomosis of the graft. There was retrograde high flow in the left IJV above the anastomosis of the graft, which fills a small left transverse venous sinus. There was also filling of the multiple abnormally enlarged leptomeningeal veins over the surface of the left cerebral and left cerebellar hemispheres. Retrograde blood flow was due to IJV stenosis which led to cerebral venous hypertension and intraparenchymal brain hemorrhage. She then underwent occlusion of her left brachiojugular dialysis graft. Thereafter, her mental status markedly improved and her headache resolved. Since IJV stenosis and hypoplastic transverse sinuses are not rare, patients with jugular grafts should probably be closely watched for symptoms of increased intracranial pressure. As awareness of vein preservation in CKD patients grows, the prevalence of CVS would probably decline in future. PMID- 22038187 TI - Gamma Knife radiosurgery as a treatment modality for low-grade pediatric brainstem gliomas: report of two cases. PMID- 22038188 TI - Fear not the IME. PMID- 22038189 TI - A bright future for JMT. PMID- 22038190 TI - 3D inverted colloidal crystals in realistic cell migration assays for drug screening applications. AB - Screening drugs for their specific impact on cell mechanics, in addition to targeting adhesion and proteolysis, will be important for successfully moderating migration in infiltrative disorders including cancer metastasis. We present 3D inverted colloidal crystals made of hydrogel as a realistic cell migration assay, where the geometry and stiffness can be set independently to mimic the tissue requirements in question. We show the utility of this 3D assay for drug screening purposes, specifically in contrast to conventional 2D migration studies, by surveying the effects of commonly used cytoskeletal toxins that impact cell mechanics. This assay allows studying large cell numbers for good statistics but at single-cell resolution. PMID- 22038191 TI - The efficacy of phonophoresis on electrophysiological studies of the patients with carpal tunnel syndrome. AB - To investigate the efficacy of phonophoresis with nonsteroid anti-inflammatory drugs (P-NSAID) and corticosteroids (P-CS) in the treatment for carpal tunnel syndrome (CTS) and to compare the efficacy of phonophoresis with local CS injection (LCSI) and splinting with a 3-month follow-up. 84 hands of 51 patients with CTS were treated by applying LCSI, P-CS, P-NSAID, and wrist splinting. Electrophysiological studies, grip strength, hand dexterity, and sensory recovery of the first three digits were assessed. Duruoz hand index (DHI) was used to assess the functional hand disability. For clinical evaluation, we used Phalen and Tinnel signs. Pain intensity was evaluated by visual analog scale. The LCIS group showed a significant improvement in pain relief and DHI, but this group had significant deterioration in the results of monofilament and pegboard tests. The P-CS group showed improvement in sensory nerve conduction velocity, distal latency, grip strength, and DHI parameters. There was a significant improvement in grip strength, pegboard test, and pain intensity in the P-NSAID group. There was improvement only in pain intensity in the splinting group. We identified marked improvement in the electrophysiological studies in the P-CS group. Splinting had no effect on hand functions, disability, and electrophysiological studies. PMID- 22038192 TI - Determining the effectiveness of various treatment modalities in carpal tunnel syndrome by ultrasonography and comparing ultrasonographic findings with other outcomes. AB - Firstly, we aimed to determine the effectiveness of various treatment modalities using ultrasonography (US), and secondly, we aimed to assess the correlations between the ultrasonographic findings and electrophysiological tests, symptom severity, functional status and physical findings. 74 hands of 47 patients with carpal tunnel syndrome (CTS) were randomly treated by applying wrist splinting alone in the neutral position (23 hands), phonophoresis with corticosteroid (PCS) (28 hands) and phonophoresis with non-steroid anti-inflamatory drug (PNSAI) (23 hands). The cross-sectional area (CSA) of the median nerve (MN) was determined by ultrasound on the initial and at the 3 months after treatment. MN conduction studies were performed on the initial visit and 3 months after treatment. The patients completed the Boston symptom severity questionnaire. For clinical evaluation, we used Phalen's and Tinel's signs. We could find reduction in CSA of MN in PCS group (P < 0.001). The CSA of MN was inversely correlated with motor sensory and median nerve conduction velocity (NCV) (r = 0.421, r = 0.213, respectively). Statistically significant correlations were not detected between ultrasonographic parameters and clinical evaluation parameters (P > 0.05) and also between ultrasonographic parameters and BQ scores (P > 0.05). Although there was some improvement in clinical parameters, ultrasonographic parameters did not change in P-NSAI group. CONCLUSION: The most effective treatment modality was P CS according to ultrasonographic and other findings. Although there were inverse correlations between the CSA of MN and sensory and motor MN conduction velocity, no relationship was found between symptom severity, functional status and US findings or electrophysiological studies. PMID- 22038193 TI - Seroprevalence and specificity of NMO-IgG (anti-aquaporin 4 antibodies) in patients with neuropsychiatric systemic lupus erythematosus. AB - Neuropsychiatric manifestations are present in 30-40% of patients with systemic lupus erythematosus (SLE). Recently, antibodies to aquaporin-4 (termed AQP4-Ab, or NMO-IgG), a water channel protein, were reported to be present in a subset of patients with SLE and neurological involvement. To evaluate the syndrome specificity and prevalence of serum NMO-IgG/anti-AQP4 antibodies in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Sera of 76 patients with SLE and neurological symptoms, 50 of whom met the ACR case definitions of NPSLE, were tested for AQP4-Ab in an indirect immunofluorescence assay employing HEK293 cells transfected with recombinant human AQP4. Only one of the examined sera was positive for NMO-IgG/AQP4-Ab. This patient suffered from TM, ranging over two vertebral segments on spinal MRI. None of the 75 NPSLE without TM was found to be seropositive for NMO-IgG/AQP4-Ab. NMO-IgG/AQP4-Ab in NPSLE were present only in a patient with TM and were not detectable in NPSLE patients with other neurological manifestations. Testing for NMO-IgG/AQP4-Ab positivity should be considered in patients presenting with SLE and TM. Non-longitudinally extensive lesions do no not exclude NMO-IgG/AQP4-Ab in patients presenting with SLE and TM. PMID- 22038194 TI - Just add tetrazole: 5-(2-pyrrolo)tetrazoles are simple, highly potent anion recognition elements. AB - We report a novel pyrrolo-tetrazole motif that encodes anion binding orders of magnitude stronger than closely related systems and suggests the general utility of amide-tetrazole exchanges for creating simple, high-affinity anion binders. PMID- 22038195 TI - DigiSwitch: a device to allow older adults to monitor and direct the collection and transmission of health information collected at home. AB - Home monitoring represents an appealing alternative for older adults considering out-of-home long term care and an avenue for informal caregivers and health care providers to gain decision-critical information about an older adults' health and well-being. However, privacy concerns about having 24/7 monitoring, especially video monitoring, in the home environment have been cited as a major barrier in the design of home monitoring systems. In this paper we describe the design and evaluation of "DigiSwitch", a medical system designed to allow older adults to view information as it is collected about them and temporarily cease transmission of data for privacy reasons. Results from a series of iterative user studies suggest that control over the transmission of monitoring data from the home is helpful for maintaining user privacy. The studies demonstrate that older adults are able to use the DigiSwitch system to monitor and direct the collection and transmission of health information in their homes, providing these participants with a way to simultaneously maintain privacy and benefit from home monitoring technology. PMID- 22038196 TI - Comparison of epitope specificity of anti-heat shock protein 60/65 IgG type antibodies in the sera of healthy subjects, patients with coronary heart disease and inflammatory bowel disease. AB - Previously, we reported on the presence of antibodies to linear epitopes of human and mycobacterial 60 kD heat shock proteins (HSP) in the sera of healthy blood donors. Since many recent findings indicate that the levels of these antibodies may be altered in coronary heart disease (CHD) and also inflammatory bowel diseases (IBD), it seemed worthwhile to compare the epitope specificity of the anti-HSP60 and anti-HSP65 antibodies in the sera of patients with these diseases to those in healthy subjects. The multipin enzyme-linked immunosorbent assay method was applied with a large overlapping set of synthetic 10-mer peptides covering selected regions of human HSP60 and Mycobacterium bovis HSP65. Sera of 12 healthy persons (HP), 14 CHD, and 14 IBD patients with the same concentration of total anti-HSP60 and HSP65 IgG antibodies were tested. We have identified CHD specific epitopes in the equatorial domain of the HSP60 protein but in neither region of the HSP65 molecule, indicating that the formation of anti-HSP60 antibodies is not or only partially due to the cross-reaction between human HSP60 and bacterial HSP65. IBD-specific epitopes were found in many regions of the HSP60 and in even more regions of the HSP65 molecule including an IBD-specific T cell epitope in region X as well. These findings indicate that the epitope specificity of the anti-human and anti-mycobacterial HSP60 antibodies associated with various diseases is different. PMID- 22038197 TI - Molecular and functional characterization of the only known hemiascomycete ortholog of the carboxyl terminus of Hsc70-interacting protein CHIP in the yeast Yarrowia lipolytica. AB - The carboxyl terminus of Hsc70-interacting protein (CHIP) is an Hsp70 co chaperone and a U-box ubiquitin ligase that plays a crucial role in protein quality control in higher eukaryotes. The yeast Yarrowia lipolytica is the only known hemiascomycete where a CHIP ortholog is found. Here, we characterize Y. lipolytica's CHIP ortholog (Yl.Chn1p) and document its interactions with components of the protein quality control machinery. We show that Yl.Chn1p is non essential unless Y. lipolytica is severely stressed. We sought for genetic interactions among key components of the Y. lipolytica protein quality control arsenal, including members of the Ssa-family of Hsp70 molecular chaperones, the Yl.Bag1p Hsp70 nucleotide exchange factor, the Yl.Chn1p and Yl.Ufd2p U-box ubiquitin ligases, the Yl.Doa10p and Yl.Hrd1p RING-finger ubiquitin ligases, and the Yl.Hsp104p disaggregating molecular chaperone. Remarkably, no synthetic phenotypes were observed among null alleles of the corresponding genes in most cases, suggesting that overlapping pathways efficiently act to enable Y. lipolytica cells to survive under harsh conditions. Yl.Chn1p interacts with mammalian and Saccharomyces cerevisiae members of the Hsp70 family in vitro, and these interactions are differently regulated by Hsp70 co-chaperones. We demonstrate notably that Yl.Chn1p/Ssa1p interaction is Fes1p-dependent and the formation of an Yl.Chn1p/Ssa1p/Sse1p ternary complex. Finally, we show that, similar to Sse1p, Yl.Chn1p can act as a "holdase" to prevent the aggregation of a heat-denatured protein. PMID- 22038198 TI - Increased levels of calcitonin gene-related peptide in serum accelerate fracture healing following traumatic brain injury. AB - The mechanisms responsible for the phenomenon of an accelerated speed of fracture healing in patients with traumatic brain injury (TBI) remain unclear. The present study was performed to test the hypothesis that TBI causes changes in calcitonin gene-related peptide (CGRP) levels in sera that enhance fracture healing. A standard closed femoral fracture was produced in rats, which were subjected to additional closed head trauma. The fracture healing was assessed 4 and 8 weeks later using micro-CT. Sera, brain tissues and muscles surrounding the fracture sites collected at 24, 48, 72 and 168 h after injury were used to detect the expression of CGRP using ELISA, immunohistochemistry and RT-PCR. Micro-CT demonstrated that fracture healing and mineralization in the TBI-fracture group occurred earlier compared to the fracture-only group. ELISA analysis revealed a high concentration of CGRP in the TBI-fracture group (P<0.05), and immunohistochemistry assay and RT-PCR analysis revealed a significant increase in CGRP in the brain and muscle of the TBI-fracture group at 168 h after fracture (P<0.001). Our results indicate that the mechanism for the enhancement of fracture-healing secondary to traumatic brain injury is correlated to the high levels of CGRP, which may be released from the brain tissue into the serum. PMID- 22038199 TI - My child has smelly urine. PMID- 22038201 TI - B-type natriuretic peptides are reliable markers of cardiac strain in CKD pediatric patients. AB - Myocardial damage and strain are common in children with chronic renal failure. The most prevalent pathologies, as defined by echocardiography, are left ventricular hypertrophy (LVH), diastolic and systolic dysfunction, and altered LV geometry. Troponin I and T, as well as B-type natriuretic peptide (BNP) and its cleavage fragment NT-proBNP, are known to be good markers of myocardial damage and stress, respectively, in the general adult population and among those with chronic kidney disease (CKD). In this study we measured the levels of troponins I and T, BNP, and NT-proBNP in a group of children and young adults with CKD stages 3-5 and determined their respective correlations with echocardiographic and laboratory abnormalities. BNP and NT-proBNP levels and their log values correlated well with the following parameters: diastolic blood pressure, estimated glomerular filtration rate, time-averaged hemoglobin levels, and LV mass. Both BNP and NT-proBNP levels, but not those of either troponin, were found to be reliable surrogate markers of strained hearts, defined as having LVH or diastolic or systolic dysfunction, in the pediatric CKD stages 3-4 group. The log NT-proBNP value was also found to be a good marker of cardiac strain in the CKD stage 5 group of patients. Serum BNP and NT-proBNP threshold concentrations of 43 and 529 pg/ml, respectively, were found to have the best sensitivity and specificity in predicting strained hearts. Based on these findings, we conclude that both BNP and NT-proBNP levels, but not those of troponins I and T, can serve as inexpensive, simple, and reliable markers of stressed hearts in the pediatric CKD patient population. PMID- 22038202 TI - Nephrotic syndrome presenting in a patient with primary Sjogren's syndrome: questions. PMID- 22038205 TI - Clofibrate-induced reduction of plasma branched-chain amino acid concentrations impairs glucose tolerance in rats. AB - It has been reported that branched-chain amino acid (BCAA) administration stimulates glucose uptake into muscles and whole body glucose oxidation in rats. The authors examined the effect of decreased plasma BCAA concentrations induced by clofibrate treatment on glucose tolerance in rats. Since clofibrate, a drug for hyperlipidemia (high serum triglyceride concentration), is a potent inhibitor of the branched-chain alpha-keto acid dehydrogenase kinase, clofibrate treatment (0.2 g/kg body weight) activated the hepatic branched-chain alpha-keto acid dehydrogenase complex, resulting in decreased plasma BCAA concentrations by 30% to 50% from the normal level. An intraperitoneal glucose tolerance test was conducted after clofibrate administration, and the results showed that peak plasma glucose concentration and the area under the curve of glucose concentration during the intraperitoneal glucose tolerance test were significantly higher in clofibrate-treated rats than in control rats. This impaired glucose tolerance in the clofibrate-treated rats was ameliorated by administration of BCAAs (0.45 g/kg body weight, leucine:isoleucine:valine = 2:1:1), which kept plasma BCAA concentrations at normal levels during the intraperitoneal glucose tolerance test. These results suggest that plasma BCAAs play an important role in maintaining normal glucose tolerance in rats. PMID- 22038204 TI - Increased urinary calcium excretion caused by ceftriaxone: possible association with urolithiasis. AB - The administration of ceftriaxone is known to be associated with biliary pseudolithiasis, although the development of urolithiasis has only rarely been reported. We treated a young male with bacterial meningitis complicated by urinary precipitates composed of ceftriaxone-calcium salt, which prompted us to study whether ceftriaxone administration predisposes children to the formation of urinary precipitates. The case-control study reported here included 83 children with bacterial pneumonia aged from 3 months to 8.9 years. The children were divided into one group of 43 children who received ceftriaxone (group A) and a second group of 40 children who received amoxicillin (group B). Paired samples of serum and urine before and after treatment were obtained from the patients in each group. There were no significant differences in demographic characteristics and blood biochemistry between the groups. However, the mean urinary calcium to creatinine ratio (uCa/Cr; mg/mg) was significantly higher in group A patients than in group B patients after treatment (0.19 vs. 0.09, respectively; p < 0.001), and analysis of the paired urine samples revealed that the uCa/Cr significantly increased after treatment only in group A patients(p < 0.001). There was a weak but non-significant relationship between the dose of ceftriaxone and the uCa/Cr in group A (p = 0.10, r = 0.24). Our results are the first to demonstrate that ceftriaxone has the potential to significantly increase urinary excretion of calcium, which may be linked to ceftriaxone-related urolithiasis or sludge. We therefore suggest that it is worthwhile monitoring the uCa/Cr levels in patients on ceftriaxone as they may be at greater risk for developing large stones and renal damage. PMID- 22038206 TI - Acrodermatitis enteropathica during adequate enteral nutrition. AB - Acrodermatitis enteropathica is a rare skin disorder of zinc deficiency. This case report describes a 91-year-old female nursing home resident who presented with a skin eruption resembling acrodermatitis enteropathica while receiving adequate enteral nutrition (EN) via a percutaneous gastrostomy tube. A low zinc level of 36 mcg/dL confirmed zinc deficiency, and treatment with oral zinc sulfate 220 mg 3 times a day resulted in rapid resolution of the skin lesions. This case supports the notion of close monitoring of patients on long-term EN for clinical manifestations of zinc deficiency, especially in the presence of an unexplained skin rash. Although micronutrient deficiencies are more prevalent in underdeveloped countries and with patients receiving parenteral nutrition, these deficiencies should be kept in mind for patients in developed countries as well as patients receiving EN. PMID- 22038207 TI - Prophylactic and therapeutic effects of a subcutaneous injection of sesame oil against iron-induced acute renal injury in mice. AB - BACKGROUND: Iron intoxication causes acute nephrotoxicity in animals and humans. Sesame oil, a healthful food, increases resistance to lipid peroxidation and protects against multiple organ injury in various animal models. The authors examined the prophylactic and therapeutic effects of a subcutaneous injection of sesame oil against iron-induced acute renal injury in mice. METHODS: Iron intoxication in mice was induced with an intraperitoneal injection (2 mg/kg) of ferric-nitrilotriacetate (Fe-NTA). Various doses of sesame oil (0, 1, 2, and 4 mL/kg, subcutaneously) were given immediately after (prophylactic) or 30 minutes after (therapeutic) the Fe-NTA injection. Renal injury was assessed by the rise in serum blood urea nitrogen (BUN) and creatinine (CRE) levels 3 hours after the Fe-NTA injection. RESULTS: One hour after the Fe-NTA injection, serum BUN and CRE levels were significantly higher in Fe-NTA-treated mice than in saline-treated controls; 3 and 6 hours after the Fe-NTA injection, they were dose-dependently and significantly lower in all sesame oil-treated groups than in the group treated only with Fe-NTA and saline. CONCLUSION: A subcutaneous injection of sesame oil had both prophylactic and therapeutic effects against iron-induced acute renal injury in mice. PMID- 22038208 TI - Impact of feeding strategies on the frequency and clearance of acid and nonacid gastroesophageal reflux events in dysphagic neonates. AB - BACKGROUND: Feeding difficulties and gastroesophageal reflux (GER) are common problems in neonates. The authors hypothesize that GER could be influenced by feeding mechanics by evaluating the effects of feeding volumes, feeding durations, feeding flow rates, and caloric density on the chemical composition and clearance of GER in dysphagic neonates. METHODS: Symptomatic dysphagic neonates (n = 35) underwent evaluation for suspected GER using pH-impedance methods. RESULTS: The proportions of acid and nonacid GER were different during the first, second, and third postprandial hours (P < .0001). Prolonged feeding duration was significantly associated with decreased total, nonacid GER and BCT (P < .03). Significant positive correlations (P < .05) were detected between feeding flow rate vs frequency of total, nonacid GER and BCT. Significant positive correlation (P = .002) was noted between feeding volume and BCT. BCT decreased with each hourly interval (analysis of variance [ANOVA] P < .05); however, ACT increased with each hourly interval (ANOVA P = .05). Comparison between BCT and ACT at each postprandial hour is remarkable for longer ACT during the second and third hours after the initiation of feed (P <= .001). No significant correlation was noted between the milk types (breast milk or formula) or caloric density with regard to the GER characteristics. Oral-fed infants had more GER events than gavage-fed infants. CONCLUSIONS: Prolonged feeding durations and slower flow rates are associated with decreased frequency of GER. Modification of feeding duration and flow rate can be a useful adjunct to ameliorate GER in dysphagic neonates. PMID- 22038209 TI - The effect of early enteral nutrition on hyperthermic intraoperative intraperitoneal chemotherapy-induced mucosal permeability following gastrectomy. AB - AIM: To investigate (1) the effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) on intestinal permeability of patients with advanced gastric cancer and (2) the protective effect of postoperative enteral nutrition (EN) on patients. METHODS: All patients were divided randomly into 3 groups: the EN group, treated with EN during postoperative period; the EN+HIIC group, treated with HIIC and postoperative EN; and the PN+HIIC group, treated with HIIC and postoperative parenteral nutrition. The lactulose/mannitol (L/M) ratio was used to evaluate the permeability of intestinal mucous. RESULTS: Compared with the ratio of L/M on the day before operation (POD-1), the ratio of L/M on POD+3 increased significantly in all 3 groups (P < .0001) and then decreased gradually. The L/M ratio of the EN and EN+HIIC groups recovered to the baseline on POD+12. In contrast, the PN+HIIC group still had an elevated L/M ratio until POD+12. The ratios of L/M in the EN+HIIC group on POD+7 and POD+12 were significantly different from those of the PN+HIIC group (0.0855 +/- 0.0462 vs 0.1298 +/- 0.063, P = .007; 0.0336 +/- 0.0235 vs 0.0616 +/- 0.0430, P = .038, respectively). CONCLUSION: Gastric cancer radical resection resulted in a significant increase in intestinal permeability. HIIC aggravated the injury of intestinal mucous permeability, which could be reversed by EN. PMID- 22038210 TI - Docosahexaenoic acid and arachidonic acid prevent essential fatty acid deficiency and hepatic steatosis. AB - OBJECTIVES: Essential fatty acids are important for growth, development, and physiologic function. alpha-Linolenic acid and linoleic acid are the precursors of docosahexaenoic and arachidonic acid, respectively, and have traditionally been considered the essential fatty acids. However, the authors hypothesized that docosahexaenoic acid and arachidonic acid can function as the essential fatty acids. METHODS: Using a murine model of essential fatty acid deficiency and consequent hepatic steatosis, the authors provided mice with varying amounts of docosahexaenoic and arachidonic acids to determine whether exclusive supplementation of docosahexaenoic and arachidonic acids could prevent essential fatty acid deficiency and inhibit or attenuate hepatic steatosis. RESULTS: Mice supplemented with docosahexaenoic and arachidonic acids at 2.1% or 4.2% of their calories for 19 days had normal liver histology and no biochemical evidence of essential fatty acid deficiency, which persisted when observed after 9 weeks. CONCLUSION: Supplementation of sufficient amounts of docosahexaenoic and arachidonic acids alone without alpha-linolenic and linoleic acids meets essential fatty acid requirements and prevents hepatic steatosis in a murine model. PMID- 22038211 TI - Eicosapentaenoic acid and docosahexaenoic acid synergistically attenuate bile acid-induced hepatocellular apoptosis. AB - BACKGROUND: Clinical studies have demonstrated improvement of parenteral nutrition (PN)-associated liver disease (PNALD) with omega3 polyunsaturated fatty acid (omega3PUFA) supplementation containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Experiments were designed to test the following hypotheses: (1) therapeutic effects of omega3PUFA are due to attenuation of cellular apoptosis induced by hydrophobic bile acid exposure, which occurs in cholestasis, and (2) attenuation of apoptosis by EPA and DHA is additive or synergistic. METHODS: Cultured HepG2 cells were treated with 50-200 uM chenodeoxycholic acid (CDCA) in the presence and absence of EPA, DHA, or EPA + DHA. Apoptosis was evaluated using cell staining with fluorescence microscopy and the Apo-ONE Homogeneous Caspase-3/7 assay. Specific apoptotic mediators were evaluated with quantitative RT-PCR. RESULTS: Treatment with EPA alone and DHA alone resulted in 22% and 9% attenuation of caspase-3/7 activity, respectively. Caspase-3/7 activity was attenuated by 52% when cells were treated with a combination of EPA and DHA (P = .0034). Treatment with EPA alone, DHA alone, and the combination of EPA and DHA all resulted in equal attenuation of apoptotic mediator gene expression. CONCLUSIONS: The combination of EPA and DHA resulted in a synergistic attenuation of bile acid-induced hepatocellular apoptosis, as assessed by caspase-3/7 activity, compared to EPA and DHA separately. The combination of EPA and DHA did not result in a synergistic attenuation of the upregulation of Fas or TRAIL-R2. These data suggest that EPA and DHA may be working via multiple intracellular pathways to attenuate bile acid-induced apoptosis. PMID- 22038213 TI - CD163 and its role in inflammation. AB - Mononuclear phagocytes represent a heterogeneous population of cells with individual subpopulations exerting different pro- or anti-inflammatory functions. CD163 is a monocyte/macrophage specific marker expressed predominantly on cells which possess strong anti-inflammatory potential. The expression of CD163 is strongly induced by anti-inflammatory mediators such as glucocorticoids and interleukin-10, while being inhibited by pro-inflammatory mediators such as interferon-gamma. CD163-expressing mononuclear phagocytes, as well as soluble CD163, may both take part in downregulating an inflammatory response. It seems, therefore, that CD163 may be an interesting target for therapeutic modulation of the inflammatory response. PMID- 22038214 TI - Stem cells and skin regeneration. AB - Stem cells represent a great hope for regenerative medicine. In adult life, stem cell deposits are kept in organ niches; the need for tissue or organ regeneration mobilizes stem cells via the SDF-1-CXCR4 regulation axis. Constant regeneration of the skin is achieved due to stem cell differentiation within the epidermis and the hair follicle; thus, skin may serve as an excellent source of stem cells. This is of paramount importance in the treatment of chronic skin wounds and burns. PMID- 22038215 TI - Different expression of cyclooxygenase-2 (COX-2) in selected nonmelanocytic human cutaneous lesions. AB - The aim of our study was to elucidate the possible involvement of COX-2 in the development and/or progression of nonmelanocytic skin lesions. To evaluate the usefulness of that enzyme as a potential molecular marker, we examined the intensity and spatial distribution of COX-2 expression in selected types of such tumors using the same immunohistochemical procedure as in our earlier studies of melanocytic cancers. We examined 20 benign epithelial lesions, 11 precancerous lesions, 21 basal cell carcinomas (BCC), 14 squamous cell carcinomas (SCC) and eight fibromas. The levels of COX-2 expression detected in benign lesions and in normal skin were comparable. Elevated expression of this protein may play a role in the development of SCC, as indicated by strong immunostaining both in SCCs and precancerous lesions. Significantly stronger staining in SCCs compared to BCCs may indicate a role of COX-2 in cancer malignancy and serve as an indicator useful for differential diagnostics of the two types of cancer. Strong staining in all skin layers of SCC may help in detecting cancer cells infiltrating surrounding skin layers. PMID- 22038216 TI - Expression of COX-2 and Bcl-2 in primary fallopian tube carcinoma: correlations with clinicopathologic features. AB - The aim of this study was to evaluate the expression of COX-2 and Bcl-2 in primary fallopian tube carcinoma (PFTC), as well as their correlations with clinicopathologic features. We studied a cohort of 33 patients with a pathological diagnosis of PFTC. Thirty normal tubal tissues used for controls were obtained from patients diagnosed with uterine myomas. Expression analysis for COX-2 and Bcl-2 was performed using the immunohistochemical technique. The rate of preoperative diagnosis was 18.2%. With a median survival of 61.0 months (95% CI: 43.2 to 78.8 months), the estimated five-year overall survival rate in the 33 patients was 39.0%. Increased expression of COX-2 and Bcl-2 was observed in tumor specimens compared to normal controls (p = 0.026; p = 0.003). The expression rate of COX-2 in node-positive tumors was significantly higher than that of node-negative tumors (p = 0.024). Moreover, the expression rate of COX-2 was statistically significantly higher in patients with infiltration through the serosa (p = 0.019). Positive significant associations were observed between Bcl-2 staining index and FIGO stage (p = 0.015), and between Bcl-2 staining and lymph node metastasis (p = 0.010). There was a significant correlation between COX-2 expression and Bcl-2 staining index (r = 0.517, p = 0.002). We conclude that COX 2 and Bcl-2 may potentially be useful prognostic markers for PFTC. The exact molecular mechanism for correlations between COX-2 and Bcl-2 remains to be elucidated. PMID- 22038217 TI - Processes of apoptosis and cell proliferation in uterine myomas originating from reproductive and perimenopausal women. AB - We studied uterine myomas originating from females of reproductive age and from females of perimenopausal age. Uterine myomas represent benign tumors of the myometrium, and they develop frequently in women of reproductive age. The frequency of uterine myomas increases with age until women reach the menopause. The study included patients with a myomatous uterus, in the reproductive age or peri-menopausal age, independently evaluating small and large myomas. Myometrial alterations in their direct vicinity were evaluated independently of the myomas. The study included evaluation of immunolocalization of two index proteins which participate in myoma cells growth control: Ki-67 nuclear antigen and caspase 3. In women of reproductive age, both in small and large myomas, elevated immunostaining of Ki-67 was noted in parallel to low levels of caspase 3 staining, which indicated the ongoing process of proliferation. In women of peri menopausal age with small or large myomas, no Ki-67 immunostaining was detected, while staining of caspase 3 manifested low levels. Proliferation in reproductive age women myomas is higher than in the peri-menopausal age. PMID- 22038218 TI - The expression profile of Fc receptor-like Y in B lymphocytes with hepatitis B virus induced diseases. AB - The Fc Receptor-like Y (FcRY) molecule is preferentially expressed by B lymphocytes and has recently been considered as a potential therapeutic target for B cell malignancies. In this study, we investigated the correlation between FcRY expression profile, B lymphocytes population and different HBV infection disease status. The FcRY expression level on B lymphocytes and the number of B lymphocytes population from peripheral blood in 27 healthy controls (HC) and 65 patients with HBV-induced diseases, including chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), were analyzed using quantitative real-time PCR and flow cytometry. The results showed the level of FcRY expression and frequency of germinal center (GC) B lymphocytes from peripheral blood were significantly correlated with the HBV-related disease status, which was highest in HCC and LC patients, lowest in healthy donors, and in the middle in patients with CHB. Our study indicates that there is a significant correlation between FcRY expression profile, B lymphocytes population and HBV-induced diseases. However, the roles of FcRY and B lymphocytes in HBV induced diseases are unclear and need further investigation. PMID- 22038219 TI - Expression of pattern recognition receptors in liver biopsy specimens of children chronically infected with HBV and HCV. AB - Pattern recognition receptors (PRRs) constitute a pivotal arm of innate immunity. Their distribution is widespread and not limited to cells of the immune system. Following our previous findings concerning the expression of Toll-like receptors (TLRs) 2, 3 and 4 in chronic viral hepatitis C of children, we wished to search for other PRRs, including other TLRs, NOD-like receptors (NLRs) and RIG-1-like helicase receptors (RLR) in infected hepatocytes. Liver biopsy fragments from ten children with chronic hepatitis B and C were used and two others in which hepatotropic virus infection was excluded. Frozen sections of liver samples were subjected to ABC immunohistochemistry (IHC) following incubation with a set of antibodies. Results of IHC findings were screened for correlation with clinical/laboratory data of patients. It was found that several PRRs could be shown in affected hepatocytes, but the incidence was higher in hepatitis C than in B. In hepatitis C, TLR1, 2, 4, NALP and RIG-1 helicase showed the most marked expression. In hepatitis B, TLR1, 3, 9, NOD1 and NALP expression were the most conspicuous. Expression PRRs in liver from hepatitis of unknown origin was much lower. It was also the case in cytospins from human hepatoma cell line. Several correlations between PRRs expression and clinical findings in patients could be shown by statistical exploration. In conclusion, this data suggests some role for PRRs in the pathogenesis of chronic viral hepatitis. PMID- 22038220 TI - Lobular neoplasia found on breast biopsy: marker of increased risk of malignancy or direct pre-cancerous lesion? AB - The aim of this study was to compare the imaging symptoms and microscopic findings in females with lobular neoplasia (LN) found on biopsy. 1,478 women who underwent primary open biopsy or surgical excision after percutaneous biopsy were reviewed. In 24 of them (1.6%), LN was found. In four patients, excisional biopsy with hook-wire localization was done primarily due to the radial scar. In 20 females, surgical excision of BIRADS 4 lesion was performed because of the presence of LN in specimens from the vacuum-assisted or core-needle percutaneous biopsy. Postoperative pathologic findings were compared to the radiological symptoms. In 13 women, LN did not produce any radiological symptoms and was an additional histologic finding existing near the other lesion: fibroadenoma and radial scar. In none of these lesions was an invasive cancer noticed. In one single patient, ductal carcinoma in situ was observed in the other segment of the breast. Invasive ductal cancer developed in the contralateral breast in one patient. In 11 patients, LN was diagnosed due to radiological symptoms produced by itself. In this group, the invasive lobular cancer was found in seven lesions (64%). Our finding suggests that LN producing suspicious radiological symptoms can be a different biologic type of this lesion when compared asymptomatic LN diagnosed which is usually found on biopsy as additional microscopic pathology. Symptomatic LN is probably associated with a higher potential of malignant transformation. PMID- 22038221 TI - Comparing the content of lipids derived from the eye lenses of various species. AB - The lipid content in the eye lens was analyzed and compared among various species in this study. The eye lens lipids of the following species were investigated: cow, horse, duck, and freshwater trout. Additionally, the lipids derived from cataractous bovine lens and from cataractous human eye lens lipoprotein complexes were analyzed. The following lipid classes were detected in clear lenses: cholesterol, sphingomyelin, phosphatidylcholine, phosphatidyletanolamine, and phosphatidylserine. In cataractous bovine lens and in lipoprotein complexes from human nuclear cataract, phosphatidyloinositol and phosphatidyloglycerol were detected. Cholesterol and sphingomyelin, essential for hypothetical formation of cholesterol-rich domains, were the most abundant lipids in the lenses of all investigated species. These two components of eye lens lipid fraction were analyzed quantitatively using thin layer chromatography and spectrophotometric assay; the other lipids were identified qualitatively using thin layer chromatography. PMID- 22038222 TI - Different distribution of c-kit positive interstitial cells of Cajal-like in children's urinary bladders. AB - We describe the presence of c-kit positive interstitial cells of Cajal-like (ICCs like) in the walls of the urinary bladders of children. An immunohistochemical study of specimens, obtained at autopsy from either the trigonum (Group A) or the corpus (Group B), was performed using antibodies against c-kit (CD 117). Histological morphometry of the immunoexpression of c-kit positive ICCs-like was performed by means of image analysis system. The c-kit positive ICCs-like were identified by their morphology and counted in the vesical muscle layer in ten adjacent high power fields, each of 0.0479 mm(2). The areas of the epithelial and subepithelial layers containing c-kit positive mast cells (rounded body with no dendritic processes) were neglected. The results were expressed as the number of ICCs-like cells per mm(2). Differences between groups were tested using unpaired Student's t-test preceded by evaluation of normality and Levene's test. Results were considered statistically significant if p < 0.05. In Group A, the mean number of ICCs-like cells was statistically significantly higher (41.5 cells/mm(2)) than in Group B (30.4 cells/mm(2)), p < 0.05. ICCs-like cells were found within the smooth muscle layer of the urinary bladder. There was a different distribution of these cells in particular parts of the bladder, which was probably due to the different roles of the trigonum and the corpus in the bladders of children. PMID- 22038223 TI - The activity of a new 2-amino-1,3,4-thiadiazole derivative 4ClABT in cancer and normal cells. AB - The 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole set are well known compounds with interesting in vitro and in vivo anti-cancer profiles. The aim of this study was an in vitro evaluation of the anti-cancer activity of a new synthesized aminothiadiazole derivative 2-(3-chlorophenyloamino)-5-(2,4 dihydroxyphenyl)- -1,3,4-thiadiazole 4ClABT. The effect on tumor cell proliferation, motility and morphology, DNA synthesis as well as the influence on normal cells was assessed. The antiproliferative activity of 4ClABT in tumor cells derived from peripheral cancers including breast carcinoma (T47D), colon carcinoma (HT-29), thyroid carcinoma (FTC-238), teratoma (P19), and T-cell leukemia (Jurkat E6.1), as well as cancers of the nervous system including rhabdomyosarcoma/medulloblastoma (TE671), brain astrocytoma (MOGGCCM) and glioma (C6) was studied by means of MTT assay. DNA synthesis level was determined in BrdU ELISA test. Wound assay model was applied for tumor cell motility assessment. Morphological changes induced by 4ClABT in cancer and normal cells were analyzed in HE staining specimens. Moreover, the influence of 4ClABT on normal cells including skin fibroblasts (HSF), hepatocytes (Fao), astroglia and neurons was studied by means of LDH assay. The tested compound inhibited the proliferation of tumor cells in dose-dependent fashion. The anti-cancer effect was attributed to decreased DNA synthesis, prominent changes in tumor cell morphology as well as reduced cell motility. In antiproliferative concentrations, 4ClABT was not toxic to normal cells. Our study showed prominent anti-cancer effects of the tested aminothiadiazole derivative in the absence of toxicity in normal cells. The obtained results confirmed the promising anti-cancer profile of previously tested 2-(monohalogenphenylamino)- -5-(2,4-dihydroxyphenyl)-1,3,4 thiadiazole derivatives (ClABT - chlorophenyl derivative, FABT and 3FABT - fluorophenyl derivatives and 4BrABT - bromophenyl derivative). The molecular mechanisms and the in vivo activity of aminothiadiazole derivatives will be the subject of further studies. PMID- 22038224 TI - p21 WAF1 and hypoxia/reoxygenation-induced premature senescence of H9c2 cardiomyocytes. AB - We have previously reported on hypoxia/reoxygenation-induced premature senescence in neonatal rat cardiomyocytes. In this research, we investigated the effects of p21(WAF1) (p21) in hypoxia/reoxygenation-induced senescence, using H9c2 cells. A plasmid overexpressing wild type p21(WAF1) and a plasmid expressing small hairpin RNA (shRNA) targeting p21(WAF1) were constructed, and transfected into H9c2 cells to control the p21 expression. Hypoxia/reoxygenation conditions were 1% O2 and 5% CO(2), balancing the incubator chamber with N(2) for 6 h (hypoxia 6 h), then 21% oxygen for 8 h (reoxygenation 8 h). Cell cycle was examined using flow cytometry. Senescence was assessed using beta-galactosidase staining. The expression of p53, p21, p16(INK4a), and cyclin D1 was assayed using Western blotting. At hypoxia 6 h, cells overexpressing p21 had a larger G1 distribution, stronger beta galactosidase activity, and lower cyclin D1 expression compared to control cells, while the opposite results and higher p53 expression were obtained in p21 knockdown cells. At reoxygenation 8 h, p21-silenced cells had a smaller percentage of G1 cells, weaker beta-galactosidase activity and lower 16(INK4a) expression, and higher cyclin D1 expression, but the overexpression group showed no difference. Taken together, this data implies that p21(WAF1) is important for the hypoxia phase, but not the reoxygenation phase, in the H9c2 senescence process. PMID- 22038225 TI - Comparative analysis of biological profiles of benign prostate hyperplasia and prostate cancer as potential diagnostic, prognostic and predictive indicators. AB - The prognosis in prostate cancer depends on several clinical-morphological factors, such as Gleason score, pTNM and preoperative PSA level. Reliable biological markers are being sought to supplement clinical-morphological data in order to better predict prognosis and to select an individualized therapeutic option. The aim of this study was a comparative analysis of the expression of biological markers, such as Hif-1alpha, bcl-2, p53, Ki-67, cyclin D1 and CD44 in BPH and prostate cancer, as well as examining their association with standard prognostic factors in prostate cancer. The immunohistochemical analysis was made on 82 formalin-fixed, paraffin- embedded tissue blocks: 43 prostate cancer specimens derived from patients who had undergone radical resection, and 39 prostate bioptates derived from patients with BPH. A positive correlation was demonstrated between Gleason score and the expression of both Hif-1alpha (R = 0.32, p < 0.05) and Ki-67 (R = 0.30, p < 0.05). Additionally, a negative correlation was demonstrated between tumor stage (pTNM) and bcl-2 expression (R = -0.35, p < 0.05). Hif-1alpha as a hypoxia marker and Ki-67 as a proliferation marker, both correlated with Gleason score, may constitute important additional prognostic indicators in prostate cancer patients. PMID- 22038226 TI - Immunodetection of aquaporin 5 in sheep salivary glands related to pasture vegetative cycle. AB - Mammalian aquaporins (AQPs) are a family of at least 13 integral membrane proteins expressed in various epithelia, where they function as channels to permeate water and small solutes. AQP5 is widely expressed in the exocrine gland where it is likely involved in providing an appropriate amount of fluid to be secreted with granular contents. As regards AQP5 expression in the salivary glands, literature is lacking concerning domestic animal species. This study was chiefly aimed at immunohistochemically investigating the presence and localization of AQP5 in sheep mandibular and parotid glands. In addition, AQP5 immunoreactivity was comparatively evaluated in animals fed with forage containing different amounts of water related to the pasture vegetative cycle, in order to shed light on the possible response of the gland to environmental modifications. Moderate AQP5-immunoreactivity was shown at the level of the lateral surface of mandibular serous demilune cells, not affected by the pasture vegetative cycle or water content. On the contrary, the parotid gland arcinar cells showed AQP5-immunoreactivity at the level of apical and lateral plasma membrane, which was slight to very strong, according to the pasture vegetative development and interannual climatic variations. AQP5 expression is likely due to its involvement in providing appropriate saliva fluidity. Indeed, the lowest AQP5 immunoreactivity was noticed when food water content increased. PMID- 22038227 TI - Decreased serum level of IL-12 in the course of ischemia and reperfusion during abdominal aortic surgery. AB - Ischemic-reperfusion injury (IRI) is defined as tissue damage, organ dysfunction or failure developed in the course of inflammatory response following ischemia and reperfusion (IR). Abdominal aortic aneurysm (AAA) repair required IR of distal parts of the body carries a risk of organ injury and postoperative mortality of between 4% and 12%. The aim of this study was the evaluation of IL 12 serum level during AAA repair in relation to IR. Blood samples were taken before surgery (Preop), before aortic unclamping (Pre-X(off)), 90 min after unclamping (90 min-X(off)) and 24 h after surgery (Postop) from 37 AAA patients; and before surgery (Preop), at 90 min of surgery (90 min-surg), at 180 min of surgery (180 min-surg) and 24 h after operation (stop) from ten patients scheduled for elective surgery of lumbar discopathy (SC); and once from ten healthy controls. IL-12 was measured using the ELISA technique. Preoperative IL 12 was higher in AAA (0.21 pg/ml) and SC (0.31 pg/ml) patients than in controls (0.05 pg/ml). A significant decrease in IL-12 (0.09 pg/ml) was observed at 90 min X(off) in comparison to the preoperative value in AAA but not in the SC group. 24 h after surgery, IL-12 levels were still low in the AAA group (0.13 pg/ml), and nonsignificantly surpassed the preoperative value in the SC group (0.36 pg/ml). We conclude that operative injury was associated with increased IL-12 levels, and IR with decreased IL-12 levels. Diminished IL-12 during AAA repair might be associated with a higher risk of postoperative complications, but this needs further evaluation. PMID- 22038228 TI - Nephrotic syndrome unfavorable course correlates with downregulation of podocyte vascular endothelial growth factor receptor (VEGFR)-2. AB - Idiopathic nephrotic syndrome (INS) in children is most commonly caused by primary glomerulopathies. Morphological lesions observed in INS might be secondary to inflammatory factors of mainly extra-renal origin. The vascular endothelial growth factor (VEGF) family is regarded as playing a crucial role in this pathomechanism. The aim of the present work was to analyze the possible relation between VEGF-C and VEGF receptor (VEGFR)-2 expressions at electron microscopy level in different INS cases. The study group comprised 18 children with minimal change disease (MCD), 30 patients diagnosed with diffuse mesangial proliferation (DMP) and 11 subjects with focal segmental glomerulosclerosis (FSGS). An indirect immunohistochemical assay employing monoclonal anti-VEGF-C and anti-VEGFR-2 antibodies was applied in the study. The immunohistochemical expression of VEGF-C within podocyte cytoplasm was significantly increased in DMP subjects who were resistant to steroids and in all FSGS patients compared to MCD children and controls (p < 0.05). VEGF-C over-expression in these cases was followed by downregulation of VEGFR-2. Nephrotic syndrome progression correlates with the downregulation of podocyte VEGFR-2. For this reason, decreased VEGFR-2 expression in the podocyte processes of children with idiopathic nephrotic syndrome might be regarded as a potent factor of unfavorable prognosis. PMID- 22038229 TI - Participation of mast cells in chronic otitis media. AB - In the pathogenesis of chronic otitis media (COM), much attention is paid to the molecular mechanisms of local inflammatory reactions in which mast cells (MCs) may be involved due to their role not only in allergic but also inflammatory processes. The aim of this study was to assess the density of mast cells in chronic otitis media in relationship to different clinical courses of COM, bacterial infections and types of disease. The MCs expression was measured immunohistochemically in paraffin-embedded granulation tissue specimens taken during surgery, by staining with a monoclonal antibody against tryptase. The density of tryptase-positive mast cells was lower in tissue samples from the group with a good clinical course than in those from the group with poor healing and recurrence (p = 0.006). There were no differences between the groups of patients with granulomatous and cholesteatomatous chronic otitis media (p = 0.66) or between the groups of patients with and without bacterial infection (p = 0.30), although the density of mast cells was lower for those with Pseudomonas aeruginosa/Proteus sp./ /Staphylococcus MRSA infection. In conclusion, the expression of mast cells in chronic otitis media granulation tissue was found to differ depending on the clinical course of the disease, but not on bacterial infection or type of COM. This may suggest that mast cells contribute to the maintenance of the inflammatory process, but not to antibacterial defense in chronic otitis media. PMID- 22038230 TI - Reproductive biology of the endangered percid Zingel asper in captivity: a histological description of the male reproductive cycle. AB - The endemic Rhodanian percid Zingel asper (Linnaeus, 1758), is usually found throughout the Rhone basin, but this fish is now in sharp decline. Understanding its reproductive physiology is important so as to be able to artificially control its reproduction with a view to re-introducing it. This study was carried out on a population obtained by artificial fertilization and bred in external tanks. Fishes were observed from the juvenile stages through to adulthood. Patterns of testicular development were defined from histological observations. Testes of Z. asper were paired, elongated and fusiform dorsocaudal organs. The two lobes of each gonad joined together to form a duct that extended to the urogenital papillae. They showed a lobular structure. The testicular lobules were of the unrestricted spermatogonial type. Up to 10 months-old, most of the males were immature: their testes showed only type A spermatogonia. The appearance of type B spermatogonia in the lobules of a testis indicated the beginning of spermatogenesis in 10 months-old fish. Spermiogenesis occurred 24 months after the fertilization and, in 26 months-old fish, the cyst opened and released spermatozoa into the lumen of lobules. The spermiation belonged to a cystic type. During the third year, histological observations pointed to the same evolution of adult gonads as during the second year. Sexual maturity was reached in captive Z. asper after two years. The spawning occurred in May in the breeding conditions. PMID- 22038231 TI - Influence of myocardial infarction on changes in the expression of angiotensin type 1 receptor in the rat prostate. AB - Angiotensin II (AngII) is the biologically active peptide of the renin angiotensin system (RAS). Tissue- based, local RAS has been identified in the prostate, testis, epididymis and coagulating glands. Experimental and clinical studies have consistently shown that myocardial infarction (MI) is associated with activation of the systemic RAS with increased concentration of angiotensin peptides in the blood and changes in expression of angiotensin receptors (AT). Changes in angiotensin receptors in the renal and cardiovascular system after MI are well recognized, but the effects of MI influence on changes in other tissue like the prostate gland are unknown. In the present study, we investigated the effect of myocardial infarction on angiotensin receptor protein and mRNA expression in the rat prostate gland. MI model was established in Wistar rats by ligating the left coronary artery (modified Selye method). The levels of AT1a-b and AT2 receptor mRNAs and proteins were measured in the rat prostate. Our study demonstrates tissue-specific changes in AT1a-b and AT2 receptor expression after myocardial infarction. The results show that MI has a strong influence on the expression of angiotensin receptor type AT1 in the prostate at the protein and mRNA level. PMID- 22038232 TI - The influence of caffeine on the biomechanical properties of bone tissue during pregnancy in a population of rats. AB - The influence of pregnancy on bone tissue metabolism is not completely understood. Caffeine also has a potentially negative influence on bones. The aim of this study was the evaluation of changes in the bones of pregnant rats under the influence of caffeine. The experiment was carried out on Wistar rats. The evaluation of rats' bone tissue quality was performed based on bone density measurements and resistance examinations. It analyzed the impact of caffeine on the degree of bone tissue mineralization and the composition of the bones. The mean value of pelvises 'wet' and 'dry' densities in a group of pregnant rats with caffeine intake was lower compared to the control group. The deformation in maximal load point of the femur shaft in the experimental group was significantly higher than in the control group. In the experimental group, the percentage of water in the bones was significantly higher, while the content of inorganic phase was significantly lower compared to the control group. The changes of biomechanical parameters in the group of pregnant rats with caffeine intake indicate its negative influence on the bone. Our results show higher plasticization of the bone shafts of the animals under the influence of caffeine. Higher deformation of bone shafts may have an effect on the statics of the skeleton. The administration of caffeine significantly affected the quantitative composition of the bone. PMID- 22038233 TI - Induction of monocyte antitumor response by human cancer cells transduced with TNF-GFP fusion gene: possible implications for immunotherapy of cancer. AB - This study was undertaken to determine how human pancreatic cancer (HPC-4) cells transduced with the TNF-GFP fusion gene (TLG) alter the antitumor response of human monocytes in vitro and whether they could act as an antitumor vaccine. In our model, HPC-4 cells were transduced with retroviral vector harboring TLG gene and designated as HPC-4(TLG). The TLG protein expression was confirmed by Western blot and flow cytometry analysis. Monocytes were co-cultured with transduced and control HPC-4 cells. The secretion of TNF, IL-10 and IL-12 was measured by ELISA. The cytotoxicity of monocytes against HPC-4 cells was determined by MTT test. The results show that the HPC-4(TLG) cells expressed membrane-bound, intracellular and secretory TLG protein. When cultured with HPC-4(TLG) cells, monocytes released a higher amount of TNF, but IL-10 and IL-12 secretion was inhibited. The pre-exposure of monocytes to HPC-4(TLG), but not to HPC-4, cells did not decrease TNF nor increase IL-10 production, thus not leading to monocyte deactivation. Also, the antitumor cytotoxicity of monocytes stimulated with HPC-4(TLG) was not downregulated, which occurred when non-transduced HPC-4 cells were used. In conclusion, compared to parental HPC-4 cells, TLG gene transduced HPC-4 cells induced stronger antitumor response of monocytes in vitro and prevented deactivation of monocytes. PMID- 22038234 TI - Expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women presenting pelvic organ prolapse. AB - The precise role of estrogen in the pathogenesis of pelvic organ prolapse (POP) is still unclear, while the results concerning the effect of selective estrogen receptor modulators on pelvic organ prolapse are contradictory. Our aim was to test whether alteration in the expression of estrogen receptors in the pelvic floor of pre- and post-menopausal women is related to genital prolapse status. The mRNA levels of ERalpha and ERbeta in 60 biopsy specimens were measured. Significantly higher expression of ERalpha and higher ERalpha/ERbeta ratio were demonstrated in post-menopausal women compared to pre-menopausal women. Higher expression of ERalpha and higher ERalpha/ERbeta ratio were detected in all studied groups with POP, thus it did not reach significance in the post menopausal group. Pre-menopausal and post-menopausal women presenting pelvic organ prolapse had no difference in the ERalpha expression. Our preliminary study may indicate that pelvic organ prolapse is associated with higher expression of ERalpha/ERbeta in the pelvic floor of both pre- and post-menopausal women; thus not reaching statistical significance in the post-menopausal women was probably due to the group's size. We believe that the inevitable changes in the estrogen receptor expression over women's different lifetimes may affect the risk of genital prolapse progression, and might contribute to the further search for appropriate selective estrogen receptor modulators as a treatment for women with pelvic organ prolapse. PMID- 22038235 TI - Phosphorylated ERK5/BMK1 transiently accumulates within division spindles in mouse oocytes and preimplantation embryos. AB - MAP kinases of the ERK family play important roles in oocyte maturation, fertilization, and early embryo development. The role of the signaling pathway involving ERK5 MAP kinase during meiotic and mitotic M-phase of the cell cycle is not well known. Here, we studied the localization of the phosphorylated, and thus potentially activated, form of ERK5 in mouse maturing oocytes and mitotically dividing early embryos. We show that phosphorylation/dephosphorylation, i.e. likely activation/inactivation of ERK5, correlates with M-phase progression. Phosphorylated form of ERK5 accumulates in division spindle of both meiotic and mitotic cells, and precisely co-localizes with spindle microtubules at metaphase. This localization changes drastically in the anaphase, when phospho-ERK5 completely disappears from microtubules and transits to the cytoplasmic granular, vesicle-like structures. In telophase oocytes it becomes incorporated into the midbody. Dynamic changes in the localization of phospho-ERK5 suggests that it may play an important role both in meiotic and mitotic division. PMID- 22038236 TI - [Acute traumatic and especially neglected traumatic hip dislocations are very rare in children]. AB - We report about the first hip arthroscopies of extracapsular neglected hip dislocations with concomitant injuries in two children (2 and 4 years old). The major problem of traumatic hip dislocation is avascular necrosis. Further problems are possible concomitant injuries. It is important not to cause further damage by therapeutic procedures. In a 4-year-old child the hip could be reduced under visualization and in a 2-year-old child with epiphyseal fracture the extent of the operation could be reduced. In both children large avulsion injuries of the ligamentum capitis femoris could be resected via hip arthroscopy. Hip arthroscopy can reduce surgical morbidity considerably and can possibly contribute to prevention of the feared avascular necrosis of the femoral head. PMID- 22038237 TI - Increase of CGRP-containing nerve fibers in the rat periodontal ligament after luxation. AB - The distribution of calcitonin gene-related peptide (CGRP) was examined in the periodontal ligament (PDL) after experimental luxation injury of the rat first molar tooth. The luxational injury increased the number of CGRP-immunoreactive (IR) nerve fibers. At 3-7 days, numerous CGRP-IR nerve fibers appeared throughout the injured PDL. These nerve fibers terminated as free nerve endings within resorption cavities. Immunohistochemistry for receptor activity modifying protein 1 (RAMP1) also demonstrated that the subunit of CGRP receptor was expressed by periodontal cells adjacent to the alveolar bone in the intact and injured PDL. RAMP1-IR cells were divided into two types; small cells with single nucleus and large cells with 2-6 nuclei. After the luxational injury, both types of RAMP1-IR cells abundantly appeared within resorption cavities. As a result, the treatment increased the number of large RAMP1-IR cells at 3-7 days and small RAMP1-IR cells at 7 days. In addition, a double immunofluorescence analysis demonstrated that CGRP-IR nerve fibers were seen away from RAMP1-IR cells in the intact PDL. After the traumatic injury, however, CGRP-IR nerve fibers appeared in the close vicinity of small and large RAMP1-IR cells at 5-7 days. The morphology and distribution of RAMP1-IR cells suggest that they contain osteoblasts and osteoclasts. By affecting osteoclasts and osteoblasts, CGRP may have effects on bone remodeling in the luxated PDL. PMID- 22038238 TI - Optimization of enzymatic hydrolysis conditions for the production of antioxidant peptides from muscles of Nemipterus japonicus and Exocoetus volitans using response surface methodology. AB - In the present study, protein of muscles of commercially important marine fishes Nemipterus japonicus and Exocoetus volitans were extracted by trypsin and their hydrolysis conditions viz., temperature, time, and enzyme to substrate concentration on degree of hydrolysis were studied by response surface methodology. The optimum values for N. japonicus was found as temperature, 30 degrees C, hydrolysis time of 100 min an enzyme/substrate concentration of 1.59% whereas, for E. volitans muscle protein, optimum hydrolysis conditions were temperature, 30 degrees C, hydrolysis time of 115 min and enzyme/substrate concentration of 1.67%. Furthermore, amino acid sequence of antioxidant peptides derived after chromatographic purification was identified by ESI-MS/MS. The analysis of peptides showed sequences as Glu-Ser-Asp-Arg-Pro (620.3 Da) and Gly Trp-Met-Gly-Cys-Trp (747.3) for N. japonicus and E. volitans muscle, respectively. The peptides contained important antioxidant amino acids and acted as good antioxidant peptides to scavenge free radicals. PMID- 22038239 TI - A fully automated human knee 3D MRI bone segmentation using the ray casting technique. AB - This study aimed at developing a fully automated bone segmentation method for the human knee (femur and tibia) from magnetic resonance (MR) images. MR imaging was acquired on a whole body 1.5T scanner with a gradient echo fat suppressed sequence using an extremity coil. The method was based on the Ray Casting technique which relies on the decomposition of the MR images into multiple surface layers to localize the boundaries of the bones and several partial segmentation objects being automatically merged to obtain the final complete segmentation of the bones. Validation analyses were performed on 161 MR images from knee osteoarthritis patients, comparing the developed fully automated to a validated semi-automated segmentation method, using the average surface distance (ASD), volume correlation coefficient, and Dice similarity coefficient (DSC). For both femur and tibia, respectively, data showed excellent bone surface ASD (0.50 +/- 0.12 mm; 0.37 +/- 0.09 mm), average oriented distance between bone surfaces within the cartilage domain (0.02 +/- 0.07 mm; -0.05 +/- 0.10 mm), and bone volume DSC (0.94 +/- 0.05; 0.92 +/- 0.07). This newly developed fully automated bone segmentation method will enable large scale studies to be conducted within shorter time durations, as well as increase stability in the reading of pathological bone. PMID- 22038241 TI - Biomechanical analysis of the effects of medial meniscectomy on degenerative osteoarthritis. AB - To investigate the effects of meniscectomy on degenerative osteoarthritis, a three-dimensional (3D) finite element (FE) model of the human lower limb is constructed from a combination of magnetic resonance (MR) images and computed tomographic (CT) images that can provide anatomically suitable boundary conditions for a knee joint. Four cases, i.e., the intact meniscus, and the partial, sub-total, and total meniscectomy of the medial meniscus are modeled and simulated. We consider that the cartilage-to-cartilage contact area and the peak contact pressure in the meniscus may be significant parameters in evaluating degenerative osteoarthritis. Partial meniscectomy can be regarded as a better treatment than sub-total/total meniscectomy, and a high possibility of degenerative osteoarthritis is anticipated after total meniscectomy. Moreover, medial meniscectomy has the potential to bring about degenerative osteoarthritis in both the medial compartment and the lateral compartment of a knee joint. PMID- 22038240 TI - Development of a comprehensive musculoskeletal model of the shoulder and elbow. AB - The Delft Shoulder and Elbow Model (DSEM), a musculoskeletal model of the shoulder and elbow has been extensively developed since its introduction in 1994. Extensions cover both model structures and anatomical data focusing on the addition of an elbow part and muscle architecture parameters. The model was also extended with a new inverse-dynamics optimization cost function and combined inverse-forward-dynamics models. This study is an update on the developments of the model over the last decade including a qualitative validation of the different simulation architectures available in the DSEM. To validate the model, a dynamic forward flexion motion was performed by one subject, of which the motion data and surface EMG-signals of 12 superficial muscles were measured. Patterns of the model-predicted relative muscle forces were compared with their normalized EMG-signals. Results showed relatively good agreement between forces and EMG (mean correlation coefficient of 0.66). However, for some cases, no force was predicted while EMG activity had been measured (false-negatives). The DSEM has been used and has the potential to be used in a variety of clinical and biomechanical applications. PMID- 22038242 TI - Validation of the H2S method to detect bacteria of fecal origin by cultured and molecular methods. AB - Using biochemical and molecular methods, this research determined whether or not the H(2)S test did correctly identify sewage-contaminated waters by being the first to use culturing and molecular methods to identify the types and numbers of fecal indicator organisms, pathogens, and other microbes present in sewage samples with positive H(2)S test results. For the culture-based method, samples were analyzed for the presence of fecal bacteria by spread plating the sewage sample onto differential and selective media for Aeromonas spp., Escherichia coli, sulfite-reducing clostridia, H(2)S-producing bacteria, and Salmonella/Shigella spp. The isolates were then: (1) tested to determine whether they were H(2)S-producing organisms and (2) identified to the genus and species level using biochemical methods. The molecular method used to characterize the microbial populations of select samples was terminal restriction fragment length polymorphisms. These experiments on sewage provided evidence that positive H(2)S tests consistently contained fecal bacteria and pathogens. There were strong relationships of agreement between the organisms identified by both methods tested. This study is an important advance in microbial water quality detection since it is focused on the evaluation of a novel, low-cost, water microbiology test that has the potential to provide millions of people worldwide access to water quality detection technology. Of prime consideration in evaluating water quality tests is the determination of the test's accuracy and specificity, and this article is a fundamental step in providing that information. PMID- 22038243 TI - Alginate beads provide a beneficial physical barrier against native microorganisms in wastewater treated with immobilized bacteria and microalgae. AB - When the freshwater microalga Chlorella sorokiniana and the plant growth promoting bacterium Azospirillum brasilense were deployed as free suspensions in unsterile, municipal wastewater for tertiary wastewater treatment, their population was significantly lower compared with their populations in sterile wastewater. At the same time, the numbers of natural microfauna and wastewater bacteria increased. Immobilization of C. sorokiniana and A. brasilense in small (2-4 mm in diameter), polymer Ca-alginate beads significantly enhanced their populations when these beads were suspended in normal wastewater. All microbial populations within and on the surface of the beads were evaluated by quantitative fluorescence in situ hybridization combined with scanning electron microscopy and direct measurements. Submerging immobilizing beads in wastewater created the following sequence of events: (a) a biofilm composed of wastewater bacteria and A. brasilense was created on the surface of the beads, (b) the bead inhibited penetration of outside organisms into the beads, (c) the bead inhibited liberation of the immobilized microorganisms into the wastewater, and (d) permitted an uninterrupted reduction of ammonium and phosphorus from the wastewater. This study demonstrated that wastewater microbial populations are responsible for decreasing populations of biological agents used for wastewater treatment and immobilization in alginate beads provided a protective environment for these agents to carry out uninterrupted tertiary wastewater treatment. PMID- 22038244 TI - Peculiarities of Pycnoporus species for applications in biotechnology. AB - The genus Pycnoporus forms a cosmopolitan group of four species belonging to the polyporoid white-rot fungi, the most representative group of homobasidiomycetes causing wood decay. Pycnoporus fungi are listed as food- and cosmetic-grade microorganisms and emerged in the early 1990s as a genus whose biochemistry, biodegradation and biotechnological properties have since been progressively detailed. First highlighted for their original metabolic pathways involved in the functionalization of plant cell wall aromatic compounds to yield high-value molecules, e.g. aromas and antioxidants, the Pycnoporus species were later explored for their potential to produce various enzymes of industrial interest, such as hydrolases and oxidases. However, the most noteworthy feature of the genus Pycnoporus is its ability to overproduce high redox potential laccase-a multi-copper extracellular phenoloxidase-as the predominant ligninolytic enzyme. A major potential use of the Pycnoporus fungi is thus to harness their laccases for various applications such as the bioconversion of agricultural by-products and raw plant materials into valuable products, the biopulping and biobleaching of paper pulp and the biodegradation of organopollutants, xenobiotics and industrial contaminants. All the studies performed in the last decade show the genus Pycnoporus to be a strong contender for white biotechnology. In this review, we describe the properties of Pycnoporus fungi in relation to their biotechnological applications and potential. PMID- 22038246 TI - Bioconversion of D-galactose to D-tagatose: continuous packed bed reaction with an immobilized thermostable L-arabinose isomerase and efficient purification by selective microbial degradation. AB - The continuous enzymatic conversion of D-galactose to D-tagatose with an immobilized thermostable L-arabinose isomerase in packed-bed reactor and a novel method for D-tagatose purification were studied. L-arabinose isomerase from Thermoanaerobacter mathranii (TMAI) was recombinantly overexpressed and immobilized in calcium alginate. The effects of pH and temperature on D-tagatose production reaction catalyzed by free and immobilized TMAI were investigated. The optimal condition for free enzyme was pH 8.0, 60 degrees C, 5 mM MnCl(2). However, that for immobilized enzyme was pH 7.5, 75 degrees C, 5 mM MnCl(2). In addition, the catalytic activity of immobilized enzyme at high temperature and low pH was significantly improved compared with free enzyme. The optimum reaction yield with immobilized TMAI increased by four percentage points to 43.9% compared with that of free TMAI. The highest productivity of 10 g/L h was achieved with the yield of 23.3%. Continuous production was performed at 70 degrees C; after 168 h, the reaction yield was still above 30%. The resultant syrup was then incubated with Saccharomyces cerevisiae L1 cells. The selective degradation of D galactose was achieved, obtaining D-tagatose with the purity above 95%. The established production and separation methods further potentiate the industrial production of D-tagatose via bioconversion and biopurification processes. PMID- 22038245 TI - Identification and immunological characteristics of chaperonin GroEL in Riemerella anatipestifer. AB - Riemerella anatipestifer (RA) infections cause major economic losses in the duck industry. In this study, an immunogenic protein, chaperonin GroEL (GroEL), was identified from the outer membrane of RA strain WJ4 by immunoproteomic assay based on matrix-assisted laser desorption/ionization time of flight mass spectrometry. The complete sequence of the encoding gene, chaperonin groEL (groEL) was amplified and determined to be 1,629 base pairs in length. groEL was then cloned into expression vector pGEX-6P-1, and the expression of the recombinant GroEL (rGroEL) in Escherichia coli strain BL21 was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting analysis. Immunization assay showed that ducklings or rabbits immunized with purified rGroEL generated 53- or 160-fold more anti-GroEL antibodies than those with no immunization. Importantly, bactericidal assay showed that rabbit anti GroEL serum killed 30.0-57.3% of bacteria representing different serotypes, while rabbit anti-bacterin serum killing activity exhibits large serotype-dependent variations between 0.2% and 63.6%. Animal challenge experiment showed that ducklings immunized with rGroEL were 50%, 37.5%, and 37.5% protected from the challenge with RA strains WJ4 (serotype 1), Th4 (serotype 2), and YXb-2 (serotype 10), respectively. In addition, groEL from 34 additional RA strains was amplified by polymerase chain reaction (PCR), and products from nine were sequenced. groEL is highly conserved among RA strains, as the DNA sequence identity was over 97.5% between WJ4 and the nine additional strains. Our results suggest that GroEL may be a good candidate for new RA vaccine development. PMID- 22038247 TI - Bioluminescence and its application in the monitoring of antimicrobial photodynamic therapy. AB - Light output from bioluminescent microorganisms is a highly sensitive reporter of their metabolic activity and therefore can be used to monitor in real time the effects of antimicrobials. Antimicrobial photodynamic therapy (aPDT) is receiving considerable attention for its potentialities as a new antimicrobial treatment modality. This therapy combines oxygen, a nontoxic photoactive photosensitizer, and visible light to generate reactive oxygen species (singlet oxygen and free radicals) that efficiently destroy microorganisms. To monitor this photoinactivation process, faster methods are required instead of laborious conventional plating and overnight incubation procedures. The bioluminescence method is a very interesting approach to achieve this goal. This review covers recent developments on the use of microbial bioluminescence in aPDT in the clinical and environmental areas. PMID- 22038248 TI - Bioremediation of beta-cypermethrin and 3-phenoxybenzaldehyde contaminated soils using Streptomyces aureus HP-S-01. AB - Using laboratory and field experiments, the ability of Streptomyces aureus HP-S 01 to eliminate beta-cypermethrin (beta-CP) and its metabolite 3 phenoxybenzaldehyde (3-PBA) in soils was investigated. In the laboratory, 80.5% and 73.1% of the initial dose of beta-CP and 3-PBA (50 mg kg(-1)) was removed in sterilized soils within 10 days, respectively, while in the same period, disappearance rate of beta-CP and 3-PBA in non-sterilized soils was higher and reached 87.8% and 79.3%, respectively. Furthermore, the disappearance process followed the first-order kinetics and the half-life (T (1/2)) for beta-CP and 3 PBA reduced by 20.3-52.9 and 133.7-186.8 days, respectively, as compared to the controls. The addition of sucrose to the soils enhanced the ability of strain HP S-01 to eliminate beta-CP and 3-PBA. Similar results were observed in the field experiments. The introduced strain HP-S-01 quickly adapted to the environment and rapidly removed beta-CP and 3-PBA without any lag phases in the field experiments. Compared with the controls, 47.9% and 67.0% of applied dose of beta CP and 3-PBA was removed from the soils without extra carbon sources and 52.5% and 73.3% of beta-CP and 3-PBA was eliminated in soils supplemented with sucrose within 10 days, respectively. Analysis of beta-CP degradation products in soil indicated that the tested strain transform beta-CP to 3-PBA and alpha-hydroxy-3 phenoxy-benzeneacetonitrile. However, both intermediates were transient and they disappeared after 10 days. Therefore, the selected actinomyces strain HP-S-01 is suitable for the efficient and rapid bioremediation of beta-CP contaminated soils. PMID- 22038249 TI - Effect of substrate and IPTG concentrations on the burden to growth of Escherichia coli on glycerol due to the expression of Lac proteins. AB - Expression of proteins unneeded for growth diverts cellular resources from making necessary protein and leads to a reduction in the growth rate of an organism. This reduction in growth rate is termed as cost. Cost plays an important role in determining the selected expression of a protein in a particular environment. Characterization of cost is important in biotechnology industries where microorganisms are used to produce foreign proteins. We have used the lactose system in Escherichia coli to quantify the cost of growth on glycerol in the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG), an inducer of the lactose system. The effect of the concentration of the carbon source, glycerol, and the inducer of Lac enzymes, IPTG, is studied. The results show that the cost is dependent on the glycerol concentration with a decreasing trend with increasing concentration of glycerol. Also as expected, the cost increases and saturates at a higher concentration of IPTG. The studies also demonstrate that the cost is higher in early exponential phase relative to late exponential phase during the growth as has been reported in the literature. Hill equation fit yielded a typical Monod-type expression for growth on glycerol with and without IPTG. An apparent half-saturation constant was defined which was used to characterize the burden on growth due to protein expression. PMID- 22038250 TI - Synthesis of novel 2,8-disubstituted indolo[3,2-b]carbazoles. AB - A new synthetic pathway towards 2,8-difunctionalised indolo[3,2-b]carbazoles was investigated. The presented method offers a short and high yielding route towards 2,8-dibromo-5,11-dihexyl-6,12-diphenyl-indolo[3,2-b]carbazole. It is demonstrated that the latter compound is a versatile building block, enabling the synthesis of a number of previously unreported 5,11-dialkyl-6,12-diphenyl-indolo[3,2 b]carbazoles in moderate to good yields, using Suzuki and Sonogashira cross coupling reaction. Furthermore it is shown that 2,8-dibromo-5,11-dihexyl-6,12 diphenyl-indolo[3,2-b]carbazole can be easily formylated, giving rise to the 2,8 diformyl-5,11-dihexyl-6,12-diphenyl-indolo-[3,2-b]carbazole. The latter compound was successfully subjected to condensation reactions. PMID- 22038251 TI - Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. AB - Visceral leishmaniasis is a potentially fatal disease endemic to large parts of Asia and Africa, primarily caused by the protozoan parasite Leishmania donovani. Here, we report a high-quality reference genome sequence for a strain of L. donovani from Nepal, and use this sequence to study variation in a set of 16 related clinical lines, isolated from visceral leishmaniasis patients from the same region, which also differ in their response to in vitro drug susceptibility. We show that whole-genome sequence data reveals genetic structure within these lines not shown by multilocus typing, and suggests that drug resistance has emerged multiple times in this closely related set of lines. Sequence comparisons with other Leishmania species and analysis of single-nucleotide diversity within our sample showed evidence of selection acting in a range of surface- and transport-related genes, including genes associated with drug resistance. Against a background of relative genetic homogeneity, we found extensive variation in chromosome copy number between our lines. Other forms of structural variation were significantly associated with drug resistance, notably including gene dosage and the copy number of an experimentally verified circular episome present in all lines and described here for the first time. This study provides a basis for more powerful molecular profiling of visceral leishmaniasis, providing additional power to track the drug resistance and epidemiology of an important human pathogen. PMID- 22038253 TI - Predictors of boys' ADHD symptoms from early to middle childhood: the role of father-child and mother-child interactions. AB - This prospective 3 year longitudinal study investigated preschool paternal and maternal parenting predictors of Attention-Deficit/Hyperactivity Disorder(ADHD) in a community sample of 93 school-age boys. Participants were recruited on the basis of inattention-hyperactivity at age 4 and fathers and mothers were observed interacting with their sons. Teachers, fathers, and mothers reported children's ADHD symptoms and impairment. Results from dimensional analysis showed that less observed paternal sensitivity and maternal positive regard predicted higher levels of inattentiveness in middle childhood, and that intrusive paternal behavior was predictive of hyperactive-impulsive behavior at school. In categorical analysis, less maternal warmth and sensitivity were predictive of later ADHD. These predictions held after statistical adjustment for the effects of preschool ADHD behaviors and conduct problems. At follow-up, parents of boys with ADHD reported more negative child-parent relationship perceptions than comparison parents. Findings highlight the importance of examining responsive parenting behaviors of both fathers and mothers in relation to multi-informant ratings of ADHD symptoms. PMID- 22038252 TI - Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania. AB - Leishmania parasites cause a spectrum of clinical pathology in humans ranging from disfiguring cutaneous lesions to fatal visceral leishmaniasis. We have generated a reference genome for Leishmania mexicana and refined the reference genomes for Leishmania major, Leishmania infantum, and Leishmania braziliensis. This has allowed the identification of a remarkably low number of genes or paralog groups (2, 14, 19, and 67, respectively) unique to one species. These were found to be conserved in additional isolates of the same species. We have predicted allelic variation and find that in these isolates, L. major and L. infantum have a surprisingly low number of predicted heterozygous SNPs compared with L. braziliensis and L. mexicana. We used short read coverage to infer ploidy and gene copy numbers, identifying large copy number variations between species, with 200 tandem gene arrays in L. major and 132 in L. mexicana. Chromosome copy number also varied significantly between species, with nine supernumerary chromosomes in L. infantum, four in L. mexicana, two in L. braziliensis, and one in L. major. A significant bias against gene arrays on supernumerary chromosomes was shown to exist, indicating that duplication events occur more frequently on disomic chromosomes. Taken together, our data demonstrate that there is little variation in unique gene content across Leishmania species, but large-scale genetic heterogeneity can result through gene amplification on disomic chromosomes and variation in chromosome number. Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression in response to environmental conditions in the host, providing a genetic basis for disease tropism. PMID- 22038254 TI - A method to investigate the diffusion properties of nuclear calcium. AB - Modeling biophysical processes in general requires knowledge about underlying biological parameters. The quality of simulation results is strongly influenced by the accuracy of these parameters, hence the identification of parameter values that the model includes is a major part of simulating biophysical processes. In many cases, secondary data can be gathered by experimental setups, which are exploitable by mathematical inverse modeling techniques. Here we describe a method for parameter identification of diffusion properties of calcium in the nuclei of rat hippocampal neurons. The method is based on a Gauss-Newton method for solving a least-squares minimization problem and was formulated in such a way that it is ideally implementable in the simulation platform uG. Making use of independently published space- and time-dependent calcium imaging data, generated from laser-assisted calcium uncaging experiments, here we could identify the diffusion properties of nuclear calcium and were able to validate a previously published model that describes nuclear calcium dynamics as a diffusion process. PMID- 22038257 TI - The role of the kidney in salt-sensitive hypertension. AB - Primary hypertension is one of the leading risk factors for cardiovascular disease. Although the pathogenesis is not completely understood, an imbalance of sodium and chloride homeostasis seems to be relevant both in the induction and in the maintenance of salt-sensitive hypertension. Besides individual renal phenotypes, salt intake is one of the most important environmental determinants of this condition. The Milan hypertensive strain (MHS) of rats is an interesting model to investigate the molecular mechanisms underling the development of salt sensitive hypertension. In young MHS rats, hypertension is anticipated by a phase of increased salt reabsorption localized along the medullary thick ascending limb associated with the up-regulation of the apical sodium-potassium-chloride cotransporter (NKCC2). Later, the frank hypertensive status of adult MHS rats is accompanied by the activation of the luminal and basal lateral transporters of sodium chloride (NaCl) in the distal convoluted tubule (DCT). Several lines of evidence have proven the key role of DCT in the maintenance of hypertension in MHS rats; more importantly, hypertensive patients carrying a mutation of alpha adducin (resembling the MHS model) have a high sensitivity to thiazides, suggesting that the Na(+)-Cl(-) cotransporter also plays a pivotal role in humans. PMID- 22038256 TI - Serum- and glucocorticoid-inducible kinase 1 in the regulation of renal and extrarenal potassium transport. AB - Serum- and glucocorticoid inducible-kinase 1 (SGK1) is an early gene transcriptionally upregulated by cell stress such as cell shrinkage and hypoxia and several hormones including gluco- and mineralocorticoids. It is activated by insulin and growth factors. SGK1 is a powerful regulator of a wide variety of channels and transporters. The present review describes the role of SGK1 in the regulation of potassium (K(+)) channels, K(+) transporters and K(+) homeostasis. SGK1-regulated K(+) channels include renal outer medullary K+ channel, Kv1.3, Kv1.5, KCNE1/KCNQ1, KCNQ4 and, via regulation of calcium (Ca(2+)) entry, Ca(2+) sensitive K(+) channels. SGK1-sensitive transporters include sodium-potassium chloride cotransporter 2 and sodium/potassium-adenosine triphosphatase. SGK1 dependent regulation of K(+) channels and K(+) transport contributes to the stimulation of renal K(+) excretion following high K(+) intake, to insulin induced cellular K(+) uptake and hypokalemia, to inhibition of insulin release by glucocorticoids, to stimulation of mast cell degranulation and gastric acid secretion, and to cardiac repolarization. Thus, SGK1 has a profound effect on K(+) homeostasis and on a multitude of K(+)-sensitive cellular functions. PMID- 22038258 TI - Claudins and renal salt transport. AB - Tight junctions (TJs) are the most apical component of junctional complexes and regulate the movement of electrolytes and solutes by the paracellular pathway across epithelia. The defining ultrastructural features of TJs are strands of transmembrane protein particles that adhere to similar strands on adjacent cells. These strands are mainly composed of linearly polymerized integral membrane proteins called claudins. Claudins comprise a multigene family consisting of more than 20 members in mammals. Recent work has shown that claudins form barriers, determined by the paracellular electrical resistance and charge selectivity, and pores in the TJ strands. The paracellular pathways in renal tubular epithelia such as the proximal tubule, which reabsorbs the largest fraction of filtered NaCl and water, are important routes for the transport of electrolytes and water. Their transport characteristics vary among different nephron segments. Multiple claudins are expressed at TJs of individual nephron segments in a nephron segment specific manner. Among them, claudin-2 is highly expressed at TJs of proximal tubules, which are leaky epithelia. Overexpression and knockdown of claudin-2 in epithelial cell lines, and knockout of the claudin-2 gene in mice, have demonstrated that claudin-2 forms high-conductance cation-selective pores in the proximal tubule. Here, we review the renal physiology of paracellular transport and the physiological roles of claudins in kidney function, especially claudin-2 and proximal tubule paracellular NaCl transport. PMID- 22038259 TI - Towards developing new strategies to reduce the adverse side-effects of nonsteroidal anti-inflammatory drugs. AB - The antipyretic and analgesic actions of nonsteroidal anti-inflammatory drugs (NSAIDs) are caused by the inhibition of prostaglandin E(2) (PGE(2)), thromboxane A(2) and prostacyclin (PGI(2)) production. Accumulating evidence suggests that the inhibition of PGE(2) production can cause adverse side-effects of NSAIDs on fluid and blood pressure regulation, such as hypertension and edema formation. Since both cyclooxygenase (COX)-1 and COX-2 isoforms contribute to the production of PGE(2), selective COX-2 inhibitors are not free of these adverse side-effects although they may be less severe. Four subtypes of PGE(2) receptors have been identified. The antipyretic action of blunted PGE(2) production is mediated predominantly by a reduced input to the prostaglandin E receptor 3 (EP(3)) pathway, whereas the analgesic action is mediated predominantly by a reduced input to the EP(1) pathway and perhaps by contributions from the other EP receptors. Accordingly, some of the adverse side-effects might be moderated by combined use of NSAIDs with selective EP(2) or EP(4) agonists that do not block the antipyretic or analgesic actions of NSAIDs that are mediated by reduced activation of EP(1) or EP(3) receptors. Moreover, EP(2) receptor-deficient mice had salt-sensitive hypertension and EP(4) receptor blockade moderated salt and water excretion and both EP(2) and EP(4) agonists had renoprotective effects. This suggests that strategies to maintain activation of EP(2) and EP(4) receptors during NSAID administration may not only reduce adverse effects but might confer additional benefits. In conclusion, enhancing EP(2) and EP(4) receptor activity by administration of selective agonists during the administration of NSAIDs has the potential to permit treating fever, inflammation and pain but with marginal adverse effects on fluid or blood pressure regulation. PMID- 22038260 TI - Cardiorenal connection in chronic kidney disease. AB - Chronic kidney disease (CKD), as defined by reduced glomerular filtration rate (<60 ml/min/1.73 m(2)) and/or the presence of renal damage for >3 months, is a significant threat for public health in modern societies. Recent epidemiological studies have demonstrated that CKD is a significant risk for cardiovascular events independently of classical risk factors such as hypertension, dyslipidemia and diabetes. The mechanisms by which CKD increases the risk of cardiovascular events are currently under intensive investigation. Among various components of CKD, microalbuminuria is of particular interest, because it is a significant risk factor not only in diabetic and hypertensive subjects but also in the general population. Microalbuminuria is also closely associated with salt sensitivity of blood pressure, and the salt sensitivity is an independent risk factor for cardiovascular disease even in normotensive subjects. Several factors are likely to be involved in such associations, including the renin-angiotensin system (RAS), oxidative stress and inflammation. In addition, there may be more specific hemodynamic mechanisms in the kidney and other vital organs underlying these associations. This review describes 'the strain vessel hypothesis' as a possible mechanism for cerebrocardiorenal connections. In addition we discuss the significance of underlying diseases as cardiovascular risks of CKD as well as the role of RAS inhibition in the management of CKD patients. PMID- 22038261 TI - Renal outer medullary potassium channel knockout models reveal thick ascending limb function and dysfunction. AB - The renal outer medullary potassium channel (ROMK) is an adenosine triphosphate sensitive inward-rectifier potassium channel (Kir1.1 or KCNJ1) highly expressed in the cortical and medullary thick ascending limbs (TAL), connecting segment (CNT) and cortical collecting duct (CCD) in the mammalian kidney, where it serves to recycle potassium (K(+)) across the apical membrane in TAL and to secrete K(+) in the CNT and CCD. ROMK channel mutations cause type II Bartter's syndrome with salt wasting and dehydration, and ROMK knockout mice display a similar phenotype of Bartter's syndrome in humans. Studies from ROMK null mice indicate that ROMK is required to form both the small-conductance (30pS, SK) K channels and the 70pS (IK) K channels in the TAL. The availability of ROMK(-/-) mice has made it possible to study electrolyte transport along the nephron in order to understand the TAL function under physiological conditions and the compensatory mechanisms of salt and water transport under the conditions of TAL dysfunction. This review summarizes previous progress in the study of K(+) channel activity in the TAL and CCD, ion transporter expression and activities along the nephron, and renal functions under physiological and pathophysiological conditions using ROMK(-/-) mice. PMID- 22038262 TI - Regulation and dysregulation of epithelial Na+ channels. AB - Epithelial Na(+) channels (ENaC) form a highly regulated pathway for the reabsorption of Na(+) from urine. This regulation can take place at a number of different levels, including synthesis of channel protein, trafficking of the protein between the surface and internal membranes, proteolytic cleavage and channel gating. This article reviews the role of these different modes of regulation under physiological conditions and considers the possible contributions of dysregulation of these processes in disease states, particularly hypertension. PMID- 22038263 TI - The roles of V1a vasopressin receptors in blood pressure homeostasis: a review of studies on V1a receptor knockout mice. AB - A prompt rise in blood pressure occurs when arginine-vasopressin is administered in quantities adequate to activate vascular V1a subtype vasopressin receptors. However, it has been controversial whether the endogenous vasopressin-V1a system contributes to the maintenance of basal blood pressure during normal development and aging. Mutant mice lacking the V1a receptor gene (V1a(-/-)) show significantly lower blood pressure compared to control mice, without a notable change in heart rate. In V1a(-/-) mice, arterial baroreceptor reflexes were attenuated due to malfunctioning baroreflex center, and the mice's circulating blood volume was significantly reduced. In line with this reduction in circulating blood volume, adrenocortical hormone release was attenuated; plasma aldosterone levels were reduced and adrenocorticotropic hormone-stimulated corticosteroid release was attenuated. In addition, V1a receptor expression was detected in macula densa cells of the kidneys, which may have facilitated renin production from the juxtaglomerular cells. Deletion of the V1a receptor appears to impact the renin-angiotensin-aldosterone system. Studies on V1a(-/-) mice revealed that non-vascular V1a receptors in the central nervous system and peripheral tissues play critical roles in the maintenance of blood pressure homeostasis. PMID- 22038264 TI - Proteolytic activation of the epithelial sodium channel and therapeutic application of a serine protease inhibitor for the treatment of salt-sensitive hypertension. AB - Proteases are involved in numerous essential biological processes including blood clotting, controlled cell death, and tissue differentiation. Prostasin, a glycosylphosphatidylinositol-anchored serine protease, has been identified as a potential regulator of the epithelial sodium channel (ENaC) function in the kidney, lung, and airways. ENaC is composed of three homologous subunits alpha, beta, and, gamma. The dual cleavage of alpha subunit by furin and gamma subunit by prostasin and furin releases inhibitory segments from ENaC, leading to the channel activation. Protease nexin-1, an endogenous prostasin inhibitor, inhibits ENaC activity through the suppression of prostasin activity, strongly suggesting the possibility that a coordinated regulation of serine proteases and serine protease inhibitors plays a key role in the sodium handling in the kidney. Camostat mesilate (CM), a synthetic serine protease inhibitor, reduced prostasin activity and subsequently decreased ENaC current. Oral administration of CM to Dahl salt-sensitive rats resulted in a significant decrease in blood pressure with an elevation of the urinary sodium/potassium ratio. These findings suggest that synthetic serine protease inhibitors such as CM might represent a new class of antihypertensive drugs in patients with salt-sensitive hypertension. PMID- 22038265 TI - Recent advances in renal urate transport: characterization of candidate transporters indicated by genome-wide association studies. AB - Humans have higher serum uric acid levels than other mammalian species owing to the genetic silencing of the hepatic enzyme uricase that metabolizes uric acid into allantoin. Urate (the ionized form of uric acid) is generated from purine metabolism and it may provide antioxidant defense in the human body. Despite its potential advantage, sustained hyperuricemia has pathogenetic causes in gout and renal diseases, and putative roles in hypertension and cardiovascular diseases. Since the kidney plays a dominant role in maintaining plasma urate levels through the excretion process, it is important to understand the molecular mechanism of renal urate handling. Although the molecular identification of a kidney-specific urate/anion exchanger URAT1 in 2002 paved the way for successive identification of several urate transport-related proteins, the entire picture of effective renal urate handling in humans has not yet been clarified. Recently, several genome-wide association studies identified a substantial association between uric acid concentration and single nucleotide polymorphisms in at least ten genetic loci including eight transporter-coding genes. In 2008, we functionally characterized the facilitatory glucose transporter family member SLC2A9 (GLUT9), one of the candidate genes for urate handling, as a voltage-driven urate transporter URATv1 at the basolateral side of renal proximal tubules that comprises the main route of the urate reabsorption pathway, in tandem with URAT1 at the apical side. In this review, recent findings concerning these candidate molecules are presented. PMID- 22038266 TI - Anti-PF4/heparin antibodies are associated with arteriovenous fistula thrombosis in non-diabetic hemodialysis patients. AB - AIM: Anti-platelet factor 4/heparin complex antibodies (anti-PF4/heparin Ab) have been found to cause heparin-induced thrombocytopenia (HIT), a clinical syndrome thrombocytopenia and thrombosis. There is still controversy as to whether the presence of anti-PF4/heparin antibodies in hemodialysis patients augments clot formation in access fistula thrombosis, peripheral artery disease (PAD), and coronary heart disease (CHD). METHODS: We enrolled 111 non-diabetic hemodialysis patients without liver cirrhosis and without an ankle-brachial index (ABI) >=1.3 (arterial calcification). ABI measurements were performed and patients with an ABI <=0.9 were defined as having PAD and included in the PAD group. ELISA was used for determination of anti-PF4/heparin Ab. Correlation factors include PAD, native arteriovenous fistula (AVF) thrombosis, platelet count, and CHD. RESULTS: Thirty-seven of 111 patients (33.3%) presented with anti-PF4/heparin Ab. Thirty eight of 111 patients (34%) had PAD; fourteen of these patients (36.8%) and 23/73 of patients without PAD (31.5%) were anti-PF4/heparin Ab-positive (P = 0.57). Fifty-two of 111 patients (46.8%) had AVF thrombosis; twenty-three of these patients (44.2%) and 14/59 of patients without AVF thrombosis (23.7%) were anti PF4/heparin Ab-positive (P = 0.02). The odds ratio for AVF thrombosis was 2.55 (95% CI 1.14-5.71) for anti-PF4/heparin Ab-positive patients. Thirty-two of 111 patients (28.8%) had thrombocytopenia (platelet count <140 * 10(3)/MUL); eleven of these patients (34.3%) and 26/79 patients without thrombocytopenia (32.9%) were anti-PF4/heparin Ab-positive (P = 0.88). Ten of 111 patients (9%) had CHD; two of these patients (20%) and 35/101 patients without CHD (34.6%) were anti PF4/heparin Ab-positive (P = 0.49). CONCLUSIONS: We found that anti-PF4/heparin Ab may contribute to an increased risk of AVF thrombosis in non-diabetic hemodialysis patients. PMID- 22038267 TI - Evaluation of iodide and iodate for adsorption-desorption characteristics and bioavailability in three types of soil. AB - Adsorption-desorption of iodine in two forms, viz., iodide (I(-)) and iodate (IO (3) (-) ), in three types of soil were investigated. The soils were: red soil developed on Quaternary red earths (REQ)- clayey, kaolintic thermic plinthite Aquult, Inceptisol soil (IS) and alluvial soil (AS)-Fluvio-marine yellow loamy soil. The isothermal curves of iodine adsorption on soils were described by Langmuir and Freundlich equation, and the maximum adsorption values (y (m)) were obtained from the simple Langmuir model. As compared with the iodide, the iodate was adsorbed in higher amounts by the soils tested. Among three soils, the REQ soil adsorbed more iodine (I(-) and IO (3) (-) ) than the IS and AS. The distribution coefficient (K (d)) of iodine in the soils decreased exponentially with increasing iodine loading concentration. Desorption of iodine in soil was increased correspondingly with increasing adsorption values. The REQ soil had a greater affinity for iodine than the IS and AS at the same iodine loadings. In the pot experiment cultivated with pakchoi (Brassica chinensis L.) and added with two exogenous iodine sources, the iodide form was quickly taken up by pakchoi and caused more toxicity to the vegetable. The rate of iodine loss from soil was higher for iodide form as compared with the iodate. The iodine bioavailability was the highest but the persistence was the weakest in AS among the three soils tested, and the REQ soil showed just the opposite trend to that of the AS soil. This study is of theoretical importance to understand the relationship between iodine adsorption-desorption characteristics and their bioavailability in different soils and it also has practical implications for seeking effective alternatives of iodine biofortification to prevent iodine deficiency disorders. PMID- 22038268 TI - Preventive effects of supplemental selenium and selenium plus iodine on bone and cartilage development in rats fed with diet from Kashin-Beck disease endemic area. AB - The purpose of this study was to investigate the effects of supplemental selenium and selenium plus iodine on bone and growth plate cartilage histology and serum biochemistic parameters in rats. Ninety-six Wistar rats were randomly divided into the following four groups: group A, the rats fed with normal diet; group B, fed with diet from Kashin-Beck disease (KBD) endemic area; group C, fed with diet from KBD endemic area supplemented with selenium; and group D, fed with diet from KBD endemic area supplemented with selenium and iodine. After 4, 8, and 12 weeks, bone and cartilage samples were collected from the rats and were examined for morphological changes in the tibial growth zone and for changes in the plate cartilage and metaphysic. Compared to the rats fed with diet from the KBD endemic area, the rats fed with the supplemental selenium or selenium plus iodine exhibited diminished necrosis of the chondrocytes in the growth plate. In the groups of rats receiving supplemental selenium and selenium plus iodine, the bone volume/tissue volume ratio (BV/TV), the trabecular thickness (Tb.Th), and the trabecular number were increased, while the trabecular separation was decreased. In the 12th week of the experiment, BV/TV and Tb.Th were significantly increased in the selenium plus iodine group compared to the selenium group. It is concluded that feeding the diet from the KBD endemic area caused necrosis of chondrocytes and dysfunctions of bone development similar to the pathological changes that are seen in KBD. Selenium and iodine protected chondrocytes in growth plate and promoted the formation of trabecular bone. The effects of selenium plus iodine on bone formation were more obvious than those of selenium alone. PMID- 22038269 TI - Effects of actinomycin D and cycloheximide on zinc status in marginally zinc deficient rats. AB - During deficient zinc intake, rats are liable to suffer zinc deficiency under the following conditions: higher protein diet, diet containing higher quality (higher nutritive value) protein, and higher dietary intake. This suggests that a higher protein nutritional status (rapid increase in body protein) in rats leads to a lower zinc nutritional status (higher zinc requirement). In contrast, it is expected that a lower protein nutritional status (lowered body protein biosynthesis) is not liable to result in a lower zinc nutritional status. Therefore, the effects of protein biosynthesis inhibitors on zinc status were studied. Actinomycin D and cycloheximide were administered to rats under a marginally zinc-deficient condition. The growth of rats was depressed and serum and femur zinc concentrations were increased by administration of protein biosynthesis inhibitors. The carcasses of rats administered protein synthesis inhibitors had a higher zinc/protein ratio than those of the respective pair-fed (calorically equivalent to the zinc-deficient group) rats. Results suggest that zinc deficiency in rats is mainly alleviated by decreased food intake with administration of protein synthesis inhibitors. Furthermore, protein biosynthesis inhibition alone alleviated zinc deficiency. PMID- 22038270 TI - Remission and recovery and their predictors in schizophrenia spectrum disorder: results from a 1-year follow-up naturalistic trial. AB - Remission and recovery are major outcome goals in schizophrenia yet their predictors have not been studied in detail. Therefore, 186 patients were examined regarding remission and recovery including their potential sociodemographic and clinical predictors 1 year after discharge. Remission was defined according to the consensus remission criteria and recovery following the definition by Liberman et al. (2002). Of the 186 patients 54% achieved remission and 26% recovery at the 1-year follow-up. The remission status at discharge was found to significantly influence remission and recovery at follow-up. A higher SOFAS score (P = 0.0002) as well as a positive attitude towards treatment at discharge (P = 0.0038) were identified to be significant predictors of remission at 1-year follow-up. Having a job (P = <0.0001) and being without pharmacological treatment at follow-up (P = 0.0113) were found to be significantly predictive of recovery. Our results underline the need to implement more specific treatment strategies to improve long-term outcome. PMID- 22038271 TI - Factors involved in making decisions to prescribe medications for psychiatric disorders by psychiatrists: a survey study. AB - The objective of this study is to understand psychiatrist's decisions to prescribe psychiatric medications. A survey questionnaire was prepared consisting of 15 factors. Each factor had a five-point Likert scale, rating the importance of each factor in making decisions to prescribe medications. Twenty-six psychiatrists at a state psychiatric hospital completed the questionnaire. The data analysis involved the frequencies of responses for each factor being compared using Chi square goodness-of-fit tests with null hypothesis that the response distribution will be centered around average score of three on the Likert scale. All the participants rated patient's symptom, severity, and diagnosis as the most important. This was followed by the patient's past experience with medications, then medication side effects, concurrent physical health problems, and medication interactions. Psychiatrist's experience with medications rated as more important than evidence from clinical trials. Finally, psychiatrists integrate evidence from research findings with personal experience, patient preferences, and clinical context in making decisions in prescribing medications for psychiatric disorders. PMID- 22038272 TI - Learning communities, social networks, and dark matter. PMID- 22038273 TI - Spontaneous self-assembly of a giant spherical metal-oxide Keplerate: addition of one building block induces "immediate" formation of the complementary one from a constitutional dynamic library. AB - The addition of dinuclear {Mo(2)} units to a dynamic library containing molybdates results in the spontaneous self-assembly of a giant spherical metal oxide species of the type {(Mo)Mo(5)}(12){Mo(2)}(30) while the required pentagonal {(Mo)Mo(5)} building blocks are "immediately" formed. PMID- 22038274 TI - The role of cremaster muscle in testicular descent in humans and animal models. AB - Testicular descent is a complex developmental process involving anatomical and hormonal regulation. The gubernaculum undergoes a "swelling reaction" during the transabdominal phase and is mainly under the control of Insulin-Like Peptide 3 (INSL-3) and Mullerian Inhibitory Substance/Anti-Mullerian Hormone (MIS/AMH). The second phase of testicular descent is regulated by androgens and calcitonin gene related peptide (CGRP) release from the sensory nucleus of the genitofemoral nerve (GFN). In rodents, the active proliferation of the gubernacular tip and cremaster muscle, its rhythmic contraction, as well as the chemotactic gradient provided by the CGRP result in eventual migration of the testis into the scrotum. This review illustrates the structural aspects and hormonal control of cremaster muscle development to better understand the mechanism of testicular descent in normal rodents and humans, compared to diseased rodent models. The analysis showed the cremaster muscle is formed from mesenchymal differentiation of the gubernacular tip and is not a direct passive extension of internal oblique muscle. Cremaster muscle matures slower than other body muscles, and the persistence of immature myogenic proteins seen in cardiac muscle allows rhythmic contraction to guide the testis into the scrotum. Finally, remodelling of the cremaster muscle enables gubernacular eversion. Further understanding of the molecular regulators governing the structural and hormonal changes in the cremaster muscle may lead to new advances in the treatment of undescended testes. PMID- 22038275 TI - [Human beings in pain : A philosophical approach]. AB - The philosophical discussion of the phenomenon of pain can help to increase the understanding of human beings in pain and to accompany them in such an experience. Pain affects a human being who has a body. The "I" of this human being cannot escape into painlessness. The pain imposes itself upon the human being who will try to withdraw from the pain but to withdraw from pain remains impossible because the human being cannot split himself up and therefore cannot establish a part of himself where his identity is not affected by pain.The pain shows how the experience of being in a body is connected to the experience of having an identity. Pain reduces the ability to act and narrows the possibility to interact with others; it affects the manner how the human is still or no longer able to address himself to others. In the reduction of his existence a human being experiences a basic condition of his existence: He is vulnerable. PMID- 22038276 TI - Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children. AB - Autoinflammatory diseases (AIDs) are characterized by recurrent, self-limiting systemic inflammation. Disorders include hereditary recurrent fever (HRF) syndromes such as hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). To determine the incidence of HIDS and report clinical and genetic characteristics together with the underlying MVK genotypes in German children, a prospective active surveillance was conducted in Germany during a period of 3 years. Monthly inquiries were sent to 370 children's hospitals by the German Paediatric Surveillance Unit (Clinic-ESPED, n1) and to two laboratories (Laboratory-ESPED, n2) performing genetic analyses. Inclusion criteria were a MVK mutation-positive patient <=16 years of age with more than three self-limiting episodes of fever >38.5 degrees C associated with increased inflammation markers. Clinical, epidemiological, and genetic data were assessed via questionnaires. Eight out of 16 patients were identified in Clinic-ESPED (n1) and 15 of 16 in Laboratory-ESPED (n2). Clinical and laboratory surveys overlapped in 7 of 16 cases. Incidence of HIDS was estimated to be 0.39 (95% CI: 0.22, 0.64) per 10(6) person-years. HIDS symptoms generally started in infancy with recurrent fever episodes lasting 3-12 (median, 4.5) days and recurring every 1-12 weeks. Fever was accompanied by abdominal pain, vomiting, diarrhea, cervical lymphadenopathy, and sometimes by headache, skin and joint symptoms. The patients carried 11 different MVK mutations mostly in compound heterozygosity (75%, 12 out of 16). The most frequent mutation was p.Val377Ile (81%, 13 out of 16). In Germany, the incidence of HIDS is very low with 0.39 per 10(6) person-years. PMID- 22038277 TI - Quality of life in patients with fibromyalgia: validation and psychometric properties of the German Quality of Life Scale (QOLS-G). AB - Our objectives were to translate the Quality of Life Scale (QOLS) into German and to evaluate its reliability and validity for the use in patients with fibromyalgia (FMS). Together with German versions of the Fibromyalgia Impact Questionnaire (FIQ), the SF-36, a tender point count (TPC) and other questionnaires, we administered the QOLS to 146 patients with FMS. Patients were asked about the severity of pain today (VAS) and the duration of symptoms. Test retest reliability was assessed using Spearman's correlations. Internal consistency was evaluated with Cronbach's alpha. Construct validity of the QOLS was evaluated by correlating the QOLS with the FIQ, the SF-36, the Beck Depression Inventory (BDI), and the Symptom Checklist (SCL-90-R) as well as with the pain variables. An exploratory factor analysis (EFA) was also conducted. Mean age was 53.1 years. Means were for pain today 6.8 and for duration of symptoms 11.8 years. Test-retest reliability for the total QOLS was rho = .91. Internal consistency was alpha = .90. Low-to-moderate correlations were obtained between the QOLS and the total FIQ (rho = -.42), the SF-36 (e.g. physical functioning rho = .37; mental health rho = .56) as well as the pain variables (VAS rho = -.11 ns; TPC rho = -.20). Psychological variables were moderately to substantially correlated with the QOLS (e.g. BDI rho = -.61). An EFA suggested a three-factor solution. The QOLS-G is a reliable and valid instrument for measuring quality of life in German patients with FMS. PMID- 22038278 TI - Validity of global physical and emotional SUDS. AB - Despite the wide-spread use of Subjective Units of Discomfort Scales, or SUDS, to measure anxiety to specific stimuli, little information has been published on the validity of such scales and even less on their use as global measures of emotional and physical discomfort. Data was examined for 182 consecutive admissions to a psychology clinic to determine the relationship of self-rating of emotional and physical discomfort to one another and of the emotional self-rating to the clinician rating of general functioning (GAF). As expected, patients' ratings of their emotional discomfort were significantly higher than ratings of their physical discomfort (t = 9.077, p < .001). Emotional SUDS were significantly and negatively related to clinicians' GAF ratings (r = - 0.439, p < .001), indicating that the two ratings measured related global constructs. Data for the 53 patients who also completed the MMPI-2 was drawn from the larger sample to determine the nature of the relationship between SUDS and two measures of general emotional distress, with patients' SUDS significantly related to both the A scale (r = 0.351, p < .05) and the neurotic index (r = 0.366, p < .01). Finally, there was a significant decrease in the emotional SUDS (t = 4.686, p < .001) but not the physical SUDS (t = 0.788, p = .434) after 3 months of psychotherapy. The data supports SUDS as global measures of both physical and emotional discomfort. PMID- 22038279 TI - The biological characteristics of glioma stem cells in human glioma cell line SHG44. AB - Gliomas are the most common tumors of the central nervous system (CNS) and a frequent cause of death. The treatment of malignant gliomas is often palliative due to their high recurrence rate. A growing body of evidence suggests that glioma may arise from cancer stem cells (CSC) correlated with neural stem cells (NSC), with the capacity for self-renewal and multipotency. CSCs have been isolated from human gliomas and numerous other solid tumors. It is assumed that a number of established malignant cell lines also contain a rare subpopulation of stem cells. This study was designed to investigate the proportion of CSCs in the human glioma cell line SHG44 and to study the limitations of CD133 immunophenotyping in glioma stem cell research. SHG44 cells were cultured in both serum-containing and serum-free medium. The similar shape in growth curves (in the exponential growth phase) revealed that most cells participated in the population amplification. Time gradient BrdU labeling and monoclonal assay revealed that almost every single cell participated in the division growth (98.82%) and possessed the ability to form clones (96.19%). No significant difference was found in the proportions of CD133+ cells in the serum-containing and serum-free groups (38.25%/37.92%). In addition, no significant difference was noted in the proportions of CD133+ cells among monoclones selected randomly in the serum-containing group. These results suggested that CD133- cells generate CD133+ cells and have the ability to form clones. Thus, we concluded that most SHG44 cells were CSCs and serum-free medium was not necessary for the generation of CSCs. In this line, CD133- cells also possessed clonogenic, self-renewal capacities and were also CSCs. PMID- 22038280 TI - High-resolution cantilever biosensor resonating at air-liquid in a microchannel. AB - We have developed a highly mass-sensitive cantilever resonating at the interface of air and liquid. The cantilever is applicable as a biosensor by measuring its resonance frequency shift associated with the selective trapping of target molecules. One surface of the cantilever facing to the liquid is functionalized for label-free detection, while the opposite side is exposed to air to improve the resonance characteristics, such as the quality factor. The quality factor at resonance is 15, which is 50% higher than the same cantilever in liquid. The beam was excited through the photothermal effect of a power modulated laser and detected by laser Doppler velocimetry. Due to the proposed configuration, the signal-to-noise-ratio is 5.7 times larger than the completely submerged case. A micro-slit around the cantilever separates the air and liquid phases at a meniscus. We analyzed the cantilever motion including the meniscus membrane, and examined the effect of surface tension by applying various solutions. A slit width of 6 MUm was found to give the best performance within the few prototypes. We measured the covalent immobilization of antibody molecules on a cantilever surface for three different concentrations: 20, 40, and 80 MUg ml(-1). The kinetics measured by both resonance frequency shift of the cantilever and fluorescent intensity showed good agreement. PMID- 22038281 TI - Ankle post-traumatic osteoarthritis: a CT arthrography study in patients with bi- and trimalleolar fractures. AB - PURPOSE: To detect radiographically occult cartilage lesions using CT arthrography (CTa) in patients with malleolar fractures treated with open reduction internal fixation and to correlate the lesions with the functional outcome score. MATERIALS AND METHODS: Twenty-one patients (13 men and 8 women, mean age 35 years, range 16-55) underwent ankle CTa after a mean postoperative period of 565 days (range 271-756). CTa images were analyzed by two radiologists. Articular surface post-traumatic collapse and subsequent cartilage defects or erosions were recorded in millimeters and in a binary mode (i.e., present if >50% of cartilage thickness) respectively. The functional outcome was assessed using the American Orthopedic Foot and Ankle Society (AOFAS) score by two orthopaedic surgeons. The statistical analysis correlated the AOFAS score with both imaging parameters and was performed with ANOVA using the MedCalc statistical package, version 11.3. RESULTS: Of the total of 12 articular surface steps recorded, 2/12 (16.67%) were anterolateral, 4/12 (33.33%) posterolateral, 5/12 (41.67%) anteromedial, and 1/12(8.33%) posteromedial. Of the total of 42 cartilage lesions, 7/42 (16.67%) were anterolateral, 14/42 (33.33%) posterolateral, 12/42 (28.57%) anteromedial, and 9/42 (21.43%) posteromedial. The mean AOFAS score was 8.67 (range 5.95-9.70). There was no statistically significant correlation between the AOFAS score and the post-traumatic internal derangement of the ankle joint (p = 0.524). CONCLUSION: CTa detects radiographically silent cartilage lesions in patients with fractures of the ankle joint. There is no correlation of the extent of lesions and the patient's AOFAS score. PMID- 22038282 TI - A quantitative method for detection of spliced X-box binding protein-1 (XBP1) mRNA as a measure of endoplasmic reticulum (ER) stress. AB - Endoplasmic reticulum (ER) stress is increasingly recognized as an important mechanism in a wide range of diseases including cystic fibrosis, alpha-1 antitrypsin deficiency, Parkinson's and Alzheimer's disease. Therefore, there is an increased need for reliable and quantitative markers for detection of ER stress in human tissues and cells. Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum can cause ER stress, which leads to the activation of the unfolded protein response (UPR). UPR signaling involves splicing of X-box binding protein-1 (XBP1) mRNA, which is frequently used as a marker for ER stress. In most studies, the splicing of the XBP1 mRNA is visualized by gel electrophoresis which is laborious and difficult to quantify. In the present study, we have developed and validated a quantitative real-time RT-PCR method to detect the spliced form of XBP1 mRNA. PMID- 22038283 TI - Neighborhood urban form, social environment, and depression. AB - We examined whether neighborhood urban form, along with the social environment, was associated with depressive symptoms in a sample of Miami residents. Using a validated measure of depressive symptoms, we found that living in neighborhoods with higher housing density was associated with fewer symptoms. A larger acreage of green spaces was also linked to fewer depressive symptoms but did not reach significance in the full model. Our results suggest that how residents use the environment matters. Living in neighborhoods with a higher density of auto commuters relative to land area, an indicator of chronic noise exposure, was associated with more symptoms. PMID- 22038284 TI - Stability of monocentric and dicentric ring minichromosomes in Arabidopsis. AB - A dicentric ring minichromosome (minidelta) was identified in transgenic Arabidopsis thaliana and added to a wild type as a supernumerary chromosome. This line is relatively stable and has been maintained for generations, notwithstanding its ring and dicentric structure. To determine the mechanism for stable transmission of minidelta, the structure and behavior of two new types of ring minichromosomes (minidelta1 and minidelta1-1) derived from minidelta were investigated. Fluorescence in situ hybridization analysis revealed that minidelta1 is dicentric just like minidelta, whereas minidelta1-1 is monocentric. The estimated sizes of minidelta1 and minidelta1-1 were 3.8~5.0 and 1.7 Mb, respectively. The sizes of the two centromeres on minidelta1 were identical (ca. 270 kb) and similar to that of minidelta1-1 (ca. 250 kb). Minidelta1 was relatively stable during mitosis and meiosis, as is minidelta, whereas minidelta1 1 was unstable during mitosis, and the number of minichromosomes per cell varied. This possibly resulted from misdivision caused by a short centromere on monocentric minidelta1-1. Transmission through the female was quite limited for all three ring minichromosomes (0-3.2%), whereas that through the male was relatively high (15.4-27.3%) compared with that of other supernumerary chromosomes in Arabidopsis. Ring structure without telomeres itself seems not to limit the female transmission. PMID- 22038285 TI - Small but mighty: the evolutionary dynamics of W and Y sex chromosomes. AB - Although sex chromosomes have been the focus of a great deal of scientific scrutiny, most interest has centred on understanding the evolution and relative importance of X and Z chromosomes. By contrast, the sex-limited W and Y chromosomes have received far less attention, both because of their generally degenerate nature and the difficulty in studying non-recombining and often highly heterochromatic genomic regions. However, recent theory and empirical evidence suggest that the W and Y chromosomes play a far more important role in sex specific fitness traits than would be expected based on their size alone, and this importance may explain the persistence of some Y and W chromosomes in the face of powerful degradative forces. In addition to their role in fertility and fecundity, the sex-limited nature of these genomic regions results in unique evolutionary forces acting on Y and W chromosomes, implicating them as potentially major contributors to sexual selection and speciation. Recent empirical studies have borne out these predictions and revealed that some W and Y chromosomes play a vital role in key sex-specific evolutionary processes. PMID- 22038286 TI - Characteristics of bone turnover, bone mass and bone strength in Spontaneously Diabetic Torii-Lepr fa rats. AB - The Spontaneously Diabetic Torii-Lepr (fa) (SDT-fa/fa) rat is a new model of obese type 2 diabetes. The SDT-fa/fa rat shows obesity and hyperglycemia at a young age compared to the Spontaneously Diabetic Torii (SDT-+/+) rat; however, bone abnormalities in the SDT-fa/fa rat have not been investigated. The objective of the present study was to investigate the effects of obese type 2 diabetes on bone turnover, bone mass, and bone strength in the SDT-fa/fa rat. Sprague-Dawley rats were used as control animals, and SDT-+/+ rats were used as non-obese type 2 diabetic rats. Serum osteocalcin and urine deoxypyridinoline levels were decreased in SDT-fa/fa rats compared to control rats at a young age. SDT-fa/fa rats showed decreases in bone mineral density and bone mineral content of the whole tibia, and shortening of the tibia and femur compared to control and SDT +/+ rats. Deterioration in bone geometrical properties of the femur midshaft such as cortical thickness and minimum moment of inertia, was observed in SDT-fa/fa rats compared to control and SDT-+/+ rats. Furthermore, trabecular bone volume of the distal femur was decreased in SDT-fa/fa rats compared to control rats. These negative effects on bone in SDT-fa/fa rats caused severe decreases in maximum load, stiffness, and energy absorption of the femur. In addition, serum levels of homocysteine, a candidate for bone fragility markers, were elevated in SDT-fa/fa rats compared to control and SDT-+/+ rats. In conclusion, the SDT-fa/fa rat may be a useful model to investigate bone abnormalities in obese type 2 diabetes. PMID- 22038287 TI - Temperature limits trail following behaviour through pheromone decay in ants. AB - In Mediterranean habitats, temperature affects both ant foraging behaviour and community structure. Many studies have shown that dominant species often forage at lower temperature than subordinates. Yet, the factors that constrain dominant species foraging activity in hot environments are still elusive. We used the dominant ant Tapinoma nigerrimum as a model species to test the hypothesis that high temperatures hinder trail following behaviour by accelerating pheromone degradation. First, field observations showed that high temperatures (> 30 degrees C) reduce the foraging activity of T. nigerrimum independently of the daily and seasonal rhythms of this species. Second, we isolated the effect of high temperatures on pheromone trail efficacy from its effect on worker physiology. A marked substrate was heated during 10 min (five temperature treatments from 25 degrees C to 60 degrees C), cooled down to 25 degrees C, and offered in a test choice to workers. At hot temperature treatments (>40 degrees C), workers did not discriminate the previously marked substrate. High temperatures appeared therefore to accelerate pheromone degradation. Third, we assessed the pheromone decay dynamics by a mechanistic model fitted with Bayesian inference. The model predicted ant choice through the evolution of pheromone concentration on trails as a function of both temperature and time since pheromone deposition. Overall, our results highlighted that the effect of high temperatures on recruitment intensity was partly due to pheromone evaporation. In the Mediterranean ant communities, this might affect dominant species relying on chemical recruitment, more than subordinate ant species, less dependent on chemical communication and less sensitive to high temperatures. PMID- 22038288 TI - Invertebrate models of lysosomal storage disease: what have we learned so far? AB - The lysosomal storage diseases (LSDs) collectively account for death in 1 in 8,000 children. Although some forms are treatable, they are essentially incurable and usually are lethal in the first decade of life. The most intractable forms of LSD are those with neuronal involvement. In an effort to identify the pathological signaling driving pathology in the LSDs, invertebrate models have been developed. In this review, we outline our current understanding of LSDs and recent findings using invertebrate models. We outline strategies and pitfalls for the development of such models. Available models of LSD in Drosophila and Caenorhabditis elegans are uncovering roles for LSD-related proteins with previously unknown function using both gain-of-function and loss-of-function strategies. These models of LSD in Drosophila and C. elegans have identified potential pathogenic signaling cascades that are proving critical to our understanding of these lethal diseases. PMID- 22038289 TI - Emotion, intent and voluntary movement in children with autism. An example: the goal directed locomotion. AB - This article focuses on the impact of intentionality on goal directed locomotion in healthy and autistic children. Closely linked with emotions and motivation, it is directly connected with movement planning. Is planning only preserved when the goal of the action appears motivating for healthy and autistic children? Is movement programming similar for autistic and healthy children, and does it vary according to the emotional valence of the object? Moving in a straight line, twenty autistic and healthy children had to retrieve a positive or aversive emotional valence object. The results suggest planning and programming are preserved in an emotionally positive situation. However, in an aversive situation, autistic children appear to have a deficit in terms of planning and sometimes programming. PMID- 22038290 TI - Detecting autism spectrum disorders in the general practitioner's practice. AB - It takes considerable time before Autism Spectrum Disorders are diagnosed. Validated diagnostic instruments are available, but not applicable to primary healthcare. By means of a case-control study we investigated whether there were differences in presented complaints and referral patterns between children with ASD (n = 49) and a control group of children without ASD (n = 81). Children with ASD were often presented as crybabies and often showed feeding problems. They visited the GP's surgery more often with anxiety disorders, enuresis, and sleeping disorders. They were referred more often to physiotherapists and speech therapists and had tympanostomy tubes and tonsillectomies more often. Depression in the parents of children with ASD was remarkably prevalent. PMID- 22038292 TI - Long-term two-dimensional pixel stability of EPIDs used for regular linear accelerator quality assurance. AB - The long-term stability of three clinical electronic portal imaging devices (EPIDs) was studied to determine if longer times between calibrations can be justified. This would make alternatives to flood-field calibration of EPIDs clinically feasible, allowing for more effective use of EPIDs for dosimetry. Images were acquired monthly for each EPID as part of regular clinical quality assurance over a time period of approximately 3 years. The images were analysed to determine (1) the long-term stability of the EPID positioning system, (2) the dose response of the central pixels and (3) the long term stability of each pixel in the imager. The position of the EPID was found to be very repeatable with variations less than 0.3 pixels (0.27 mm) for all imagers (1 standard deviation). The central axis dose response was found to reliably track ion chamber measurements to better than 0.5%. The mean variation in pixel response (1 standard deviation), averaged over all pixels in the EPID, was found to be at most 0.6% for the three EPIDs studied over the entire period. More than 99% of pixels in each EPID showed less than 1% variation. Since the EPID response was found to be very stable over long periods of time, an annual calibration should be sufficient in most cases. More complex dosimetric calibrations should be clinically feasible. PMID- 22038291 TI - Differentiating high-functioning autism and social phobia. AB - Both high-functioning autism (HFA) and social phobia (SP) involve profound social interaction deficits. Although these disorders share some similar symptoms, they are conceptualized as distinct. Because both HFA and SP are defined behaviorally, the degree of overlap between the two disorders may result in misinterpretation of symptoms. However, the deficits in each disorder differ, particularly in areas of social interaction, emotion recognition and expression, and communication. This paper reviews the literature that informs our current understanding of the behavioral overlaps and differences in HFA and SP. The review also addresses the implications of our current knowledge of these two disorders for differential diagnosis, treatment, and future research. Interdisciplinary, developmentally oriented research may help extend current approaches to HFA and SP. PMID- 22038293 TI - Status of robotic assistance--a less traumatic and more accurate minimally invasive surgery? AB - PURPOSE: Robotic assistance is considered one innovation within abdominal surgery over the past decade that has the potential to compensate for the drawbacks of conventional laparoscopy, such as limited degree of freedom, 2D vision, fulcrum, and pivoting effect. Robotic systems provide corresponding solutions as 3D view, intuitive motion and enable additional degrees of freedom. This review provides an overview of the history of medical robotics, experimental studies, clinical state-of-the-art and economic impact. METHODS: The Medline database was searched for the terms "robot, telemanipulat, and laparoscop." A total of 2,573 references were found. All references were considered for information on robotic assistance in advanced laparoscopy. Further references were obtained through cross referencing the bibliography cited in each work. RESULTS: In experimental studies, current robotic systems showed superior handling and ergonomics compared to conventional laparoscopic techniques. In gynecology especially for hysterectomy and in urology especially for prostatectomy, two procedures formerly performed via an open approach, the robot enables a laparoscopic approach. This results in reduced need for pain medication, less blood loss, and shorter hospital stay. Within abdominal surgery, clinical studies were generally unable to prove a benefit of the robot. While the benefit still remains open to discussion, robotic systems are spreading and are available worldwide in tertiary centers. CONCLUSION: Robotic assistance will remain an intensively discussed subject since clinical benefits for most procedures have not yet been proven. The most promising procedures are those in which the robot enables a laparoscopic approach where open surgery is usually required. PMID- 22038294 TI - Predictors and outcome of early recurrence after resection of hepatic metastases from colorectal cancer. AB - PURPOSE: This study aimed to investigate the risk factors for early recurrence in patients who had undergone curative resection of colorectal liver metastases (CRLM) and to evaluate the outcome after recurrence. METHODS: A total of 119 patients were divided into 2 groups: an early recurrence group (n = 54) who had recurrence within 2 years of curative resection of CRLM and a 2-year recurrence free group (n = 65) who remained disease-free for at least 2 years following surgery. RESULTS: During the initial 5-year period after surgery, 4 out of 65 patients (6%) in the 2-year recurrence-free group and 29 out of 54 patients (54%) in the early recurrence group died. Multivariate analysis showed that postoperative morbidity was an independent predictor of early recurrence after curative resection of CRLM. CONCLUSIONS: Early recurrence is the leading cause of death within 5 years after curative resection of CRLM. Postoperative morbidity increases the risk of early recurrence in these patients. A reduction in perioperative morbidity may, therefore, improve the outcome of curative resection, as well as reducing medical costs. PMID- 22038296 TI - Impact of smoking on disease phenotype and postoperative outcomes for Crohn's disease patients undergoing surgery. AB - AIM: Whether smoking affects disease distribution, phenotype, and perioperative outcomes for Crohn's disease (CD) patients undergoing surgery is not well characterized. The aim of this study is to evaluate the impact of smoking on disease phenotype and postoperative outcomes for CD patients undergoing surgery METHODS: Prospectively collected data of CD patients undergoing colorectal resection were evaluated. CD patients who were current smokers (CS) were compared to nonsmokers (NS) and ex-smokers (ES) for disease phenotype, anatomic site involved, procedures performed, postoperative outcomes, and quality of life using the Cleveland Global Quality of Life instrument (CGQL). RESULTS: Of 691 patients with a diagnosis of CD requiring surgery 314 were classified as CS, 330 as NS, and 47 as ES. CS and ES in comparison to NS were significantly older at diagnosis of Crohn's disease (mean, 29.3 vs. 29.2 vs. 26.3 years) (P = 0.001) and older at the time of primary surgery (mean, 42.9 vs. 48.4 vs. 39 years) (P = 0.001) with a greater frequency of diabetes. In all groups requiring surgery, there was a significant change in disease phenotype from the time of diagnosis to surgical intervention. The predominant phenotype at diagnosis was inflammatory which changed to stricturing and penetrating as the dominant phenotypes at time of surgery. All groups had a significant improvement in CGQL scores post-surgery with the greatest benefit observed in NS. Postoperative complications and 30-day readmission rates were similar between all groups. CONCLUSIONS: The findings of this study show that in patients with CD, disease phenotype changes over time. This occurs independent of smoking. Smoking does not appear to predispose to complications for CD patients undergoing surgery. CS and ES have a persistently reduced quality of life in comparison to NS post-surgery. PMID- 22038295 TI - Preoperative short-term parenteral administration of polyunsaturated fatty acids ameliorates intestinal inflammation and postoperative ileus in rodents. AB - PURPOSE: Abdominal surgery results in an inflammation of the intestinal muscularis externa (ME), subsequently leading to postoperative ileus (POI). Polyunsaturated fatty acids (PUFA) are known to modulate inflammation. The aim of this study was to analyze the effect of preoperative parenteral administration of marine (n-3) or soybean (n-6) PUFA lipid emulsions (PUFA-LE) on POI and tissue fatty acid profiles. METHODS: Rodents underwent intestinal manipulation (IM) after 5 days of parenteral administration of 10-mL/kg body weight saline, (n-3), or (n-6) PUFA-LE. Sham animals received saline treatment without IM. In rats, postoperative inflammation was quantified by ME neutrophil levels and NO production in organ culture, and ME function was determined by an in vitro contractility measurement. Additionally, in vivo gastrointestinal transit (GIT) was analyzed in mice. Lipopolysaccharide-induced IL-6 expression of rat bone marrow-derived mononuclear cells and ME was analyzed. Fatty acids were measured by gas chromatography in rat blood, bone marrow cells, and ME. RESULTS: The (n-3) PUFA-LE reduced neutrophil levels and NO production after IM and improved in vitro jejunal contractility and GIT time. The (n-6) PUFA-LE significantly reduced postoperative inflammation and tended to improve intestinal motility (P < 0.06). Interestingly, (n-6) PUFA-LE significantly reduced the levels of arachidonic acid in ME (-63%), while (n-3) PUFA-LE reduced arachidonic acid (-20%) and additionally raised EPA (+550%). CONCLUSION: Short-term preoperative parenteral administration of (n-3) or (n-6) PUFA-LE significantly alters tissue-specific fatty acid profiles. Preoperative parenteral PUFA-LE supplementation, preferably by marine (n-3) PUFA, ameliorates postoperative intestinal inflammation and dysmotility and could be a promising therapeutic option in POI prophylaxis. PMID- 22038298 TI - Ruthenium-catalysed oxidative synthesis of heterocycles from alcohols. AB - Ruthenium-catalysed hydrogen transfer has been successfully used for the conversion of alcohols into either 2,3-dihydroquinazolines or quinazolines. The choice of reaction conditions allows for the selective formation of either heterocycle and the methodology can also be applied to the sulfonamide analogue. PMID- 22038297 TI - Workplace-based work disability prevention interventions for workers with common mental health conditions: a review of the literature. AB - INTRODUCTION: To summarize evidence on workplace-based work disability prevention (WDP) interventions in workers with common mental health conditions (CMHCs). Primary outcomes of interest were work absence duration and work functioning; secondary outcomes were quality of life, and economic costs. METHODS: We conducted a systematic literature search in 5 electronic databases (MEDLINE, EMBASE, CINAHL, PsychINFO, Web of Science) for studies published from 2007 to 2009. Two reviewers screened for studies: (1) Targeting workers with CMHCs absent from, or struggling at, work; (2) evaluating workplace-based WDP interventions; (3) assessing our primary outcome(s); and (4) with controlled trials. Quality assessment (using 29 criteria) was performed by two reviewers. RESULTS: Our search yielded 671 abstracts: 8 eligible studies and of sufficient quality. We identified three main intervention elements: (a) Facilitation of access to clinical treatment; (b) Workplace-based high-intensity psychological intervention; and (c) Facilitation of navigation through the disability management system. Moderate evidence was found that facilitation of treatment improved work functioning, quality of life and economic outcomes, with limited evidence for work absence duration. Moderate evidence was found that psychological interventions, primarily cognitive-behavioral therapy, improved work functioning, quality of life, and economic outcomes. Moderate evidence indicated that facilitation of navigation through the disability management system improved work absence duration. CONCLUSIONS: Workplace-based interventions could improve work disability outcomes for workers with CMHCs. Facilitation of access to clinical treatment, and workplace-based high-intensity psychological intervention were most effective in improving work functioning and quality of life, and in reducing costs. PMID- 22038299 TI - A multi-component domino reaction for the direct access to polyfunctionalized indoles via intermolecular allylic esterification and indolation. AB - A novel multi-component reaction for the synthesis of polyfunctionalized indoles and bis-indoles has been established. The reaction pathways were controlled by varying enamines with different substitution patterns to give polyfunctionalized indoles and bis-indoles selectively. The reaction proceeds at a fast speed within 15-30 min with water as the major byproduct, which makes work-up convenient. PMID- 22038301 TI - Neovascularization and hematopoietic stem cells. AB - Vasculogenesis and angiogenesis are the major forms of blood vessel formation. Angiogenesis is the process where new vessels grow from pre-existing blood vessels, and is very important in the functional recovery of pathological conditions, such as wound healing and ischemic heart diseases. The development of better animal model and imaging technologies in past decades has greatly enriched our understanding on vasculogenesis and angiogenesis processes. Hypoxia turned out to be an important driving force for angiogenesis in various ischemic conditions. It stimulates expression of many growth factors like vascular endothelial growth factor, platelet-derived growth factor, insulin-like growth factor, and fibroblast growth factor, which play critical role in induction of angiogenesis. Other cellular components like monocytes, T cells, neutrophils, and platelets also play significant role in induction and regulation of angiogenesis. Various stem/progenitor cells also being recruited to the ischemic sites play crucial role in the angiogenesis process. Pre-clinical studies showed that stem/progenitor cells with/without combination of growth factors induce neovascularization in the ischemic tissues in various animal models. In this review, we will discuss about the fundamental factors that regulate the angiogenesis process and the use of stem cells as therapeutic regime for the treatment of ischemic diseases. PMID- 22038300 TI - Homocysteine-induced apoptosis in endothelial cells coincides with nuclear NOX2 and peri-nuclear NOX4 activity. AB - Apoptosis of endothelial cells related to homocysteine (Hcy) has been reported in several studies. In this study, we evaluated whether reactive oxygen species (ROS)-producing signaling pathways contribute to Hcy-induced apoptosis induction, with specific emphasis on NADPH oxidases. Human umbilical vein endothelial cells were incubated with 0.01-2.5 mM Hcy. We determined the effect of Hcy on caspase-3 activity, annexin V positivity, intracellular NOX1, NOX2, NOX4, and p47(phox) expression and localization, nuclear nitrotyrosine accumulation, and mitochondrial membrane potential (DeltaPsi m). Hcy induced caspase-3 activity and apoptosis; this effect was concentration dependent and maximal after 6-h exposure to 2.5 mM Hcy. It was accompanied by a significant increase in DeltaPsi m. Cysteine was inactive on these parameters excluding a reactive thiol group effect. Hcy induced an increase in cellular NOX2, p47(phox), and NOX4, but not that of NOX1. 3D digital imaging microscopy followed by image deconvolution analysis showed nuclear accumulation of NOX2 and p47(phox) in endothelial cells exposed to Hcy, but not in control cells, which coincided with accumulation of nuclear nitrotyrosine residues. Furthermore, Hcy enhanced peri-nuclear localization of NOX4 coinciding with accumulation of peri-nuclear nitrotyrosine residues, a reflection of local ROS production. p47(phox) was also increased in the peri-nuclear region. The Hcy-induced increase in caspase-3 activity was prevented by DPI and apocynin, suggesting involvement of NOX activity. The data presented in this article reveal accumulation of nuclear NOX2 and peri-nuclear NOX4 accumulation as potential source of ROS production in Hcy-induced apoptosis in endothelial cells. PMID- 22038302 TI - The prooxidant action of dietary antioxidants leading to cellular DNA breakage and anticancer effects: implications for chemotherapeutic action against cancer. AB - Plant-derived dietary antioxidants have attracted considerable interest in recent past for their ability to induce apoptosis and regression of tumors in animal models. While it is believed that the antioxidant properties of these agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, it could not account for apoptosis induction and chemotherapeutic observations. In this article, we show that dietary antioxidants can alternatively switch to a prooxidant action in the presence of transition metals such as copper. Such a prooxidant action leads to strand breaks in cellular DNA and growth inhibition in cancer cells. Further, the cellular DNA breakage and anticancer effects were found to be significantly enhanced in the presence of copper ions. Moreover, inhibition of antioxidant-induced DNA strand breaks and oxidative stress by Cu(I)-specific chelators bathocuproine and neocuproine demonstrated the role of endogenous copper in the induction of the prooxidant mechanism. Since it is well established that tissue, cellular, and serum copper levels are considerably elevated in various malignancies, such a prooxidant cytotoxic mechanism better explains the anticancer activity of dietary antioxidants against cancer cells. PMID- 22038303 TI - Apoptosis of Dalton's lymphoma due to in vivo treatment with emodin is associated with modulations of hydrogen peroxide metabolizing antioxidant enzymes. AB - The evolving concept of pro-oxidative mechanism-based antitumor activity of emodin (1,3,8-trihydroxy-6-methyl anthraquinone), derived mainly from in vitro studies, needs to be defined for in vivo tumor models. The present article describes apoptosis and regression of Dalton's lymphoma (DL) in mice by emodin vis a vis modulations of hydrogen peroxide (H2O2) metabolizing antioxidant enzymes in the tumor cells in vivo. A non-toxic dose (40 mg/kg bw) of emodin, given intraperitoneally to the DL bearing mice daily up to 12th post DL transplantation day, caused a significant decline (P < 0.05) in the number of viable DL cells and could significantly increase life span of the DL mice (P < 0.01). A significant decline in Bcl2/Bax ratio consistent with the release of mitochondrial cytochrome c release in DL cells from emodin-treated DL mice suggested that emodin could induce mitochondrial pathway of apoptosis in the DL cells in vivo. Apoptosis of DL cells by emodin was further confirmed by the appearance of smaller DNA fragments on DNA ladder analysis. Over activation of both, the Cu-Zn-superoxide dismutases (SOD1) and Mn-SOD (SOD2), has been found correlated with the tumor suppression. Emodin caused significant increases in the expression and activity of SOD1 and SOD2 in the DL cells. H2O2 produced by SODs is degraded by catalase and glutathione peroxidase in the cells. Both these enzymes were observed to be declined significantly with a concomitant increment in H2O2 concentration (P < 0.01) in the DL cells from emodin-treated DL mice. It is concluded that emodin is able to induce mitochondrial pathway of apoptosis in the DL cells in vivo via reciprocal modulations of H2O2 producing and degrading antioxidant enzymes. PMID- 22038304 TI - Piperine attenuates cardiovascular, liver and metabolic changes in high carbohydrate, high fat-fed rats. AB - Black pepper is used worldwide to enhance food flavor. We investigated dietary supplementation with piperine, the active principle of black pepper, to high carbohydrate, high fat (HCHF) diet-fed rats as a model of human metabolic syndrome. Rats were fed with either HCHF diet (carbohydrate, 52%; fat, 24%; 25% fructose in drinking water) or cornstarch (CS) diet for a total of 16 weeks. Diets of the treatment groups (CS + piperine and HCHF + piperine) were supplemented with piperine for the last 8 weeks of this protocol. After 16 weeks, rats fed with HCHF diet developed hypertension, elevated oxidative stress and inflammation-induced cardiac changes (infiltration of inflammatory cells in heart, increase in count and degranulation of mast cells in heart, cardiac fibrosis and increase in ventricular stiffness), reduced responsiveness of aortic rings, impaired glucose tolerance, abdominal obesity together with liver fibrosis, fat deposition and increased plasma liver enzymes. Supplementation with piperine (375 mg/kg food; approximately 30 mg/kg/day) in HCHF-fed rats normalized blood pressure, improved glucose tolerance and reactivity of aortic rings, reduced plasma parameters of oxidative stress and inflammation, attenuated cardiac and hepatic inflammatory cell infiltration and fibrosis and improved liver function. These changes clearly suggest that piperine reduces symptoms of human metabolic syndrome in HCHF-fed rats by reducing inflammation and oxidative stress. PMID- 22038305 TI - Gender differences in colorectal cancer during the past 20 years in Taiwan. AB - PURPOSE: Gender differences in colorectal cancer (CRC) incidence have been previously reported. We designed this population-based study to determine if this gender difference was restricted to specific patient subgroups. METHODS: Using the Taiwan Cancer Registry database, we identified a total of 124,314 CRCs registered from 1988 to 2007. We compared the incidence of CRCs by gender in all CRCs, in colon and rectal cancers considered separately, and in right-sided versus left-sided colon cancers. RESULTS: In individuals aged 50 years and older, the incidence of CRCs was lower in females compared with males. For right-sided colon cancers, the incidence in both genders was similar. Because the proportion of right-sided colon cancer accounted for only one fourth of the total CRCs, its influence on the incidence of total CRCs is reduced. CONCLUSIONS: Although the incidence of total CRCs is male dominant, the actual gender difference in CRC incidence in Taiwan is limited to the left side of the colon. PMID- 22038306 TI - Quality of surgical care, local recurrence, and survival in patients with low- and midrectal cancers following multimodal therapy. AB - PURPOSE: To assess the quality of surgical care and outcome following multimodal treatment for low- and midrectal cancers, focusing on differences between low anterior and abdominoperineal resections. METHODS: From 1999 to 2007, 179 patients underwent low anterior resection (LAR), abdominoperineal resection (APR), or proctocolectomy for low- or midrectal cancers. Preoperative (chemo)radiotherapy was given according to local guidelines and adjuvant postoperative chemotherapy in stage III disease. Outcome together with clinical and histopathological data were analyzed in relation to the type of surgery performed. RESULTS: The postoperative mortality was 2.2%; morbidity, 39.6%; reoperation rate, 8.4%; and readmission rate, 16.0%. Involved circumferential resection margin (CRM <= 1 mm) rate was 4.5% (APR 9.1% vs. LAR 2.6%, p = 0.046). Intraoperative bowel perforation occurred in 5.5% of APRs. Anastomotic leak rate was 15.3%. The 5-year overall survival of the 179 patients was 68.5 %; disease specific survival, 82.2%; and local recurrence rate, 6.3%. The overall, disease specific, and disease-free survival rates in the 162 patients treated for cure were 73.1%, 84.6%, and 78.3%, and local recurrence rate was 4.4% with no significant differences between LAR and APR. CRM was the only independent predictor of local recurrence and CRM, tumor stage, and level independent predictors of disease-free survival. CONCLUSIONS: Quality of surgical care was in line with the current international standards. CRM was an independent predictor for local recurrence and CRM, tumor stage, and level independent prognostic factors for disease-free survival. Neither the type of surgery (LAR vs. APR) nor the surgical approach (laparoscopic vs. open) influenced the oncologic outcome. PMID- 22038307 TI - The peripheral zone of the prostate is more prone to tumor development than the transitional zone: is the ETS family the key? AB - Predisposition to develop prostate cancer (PCA) varies among the prostate zones, with the peripheral zone (PZ) more prone to tumor development than the transitional zone (TZ). In view of the fact that molecular differences between the zones may explain this difference, combined with the findings that translocations between TMPRSS2 and several ETS members are frequently observed in PCA, we hypothesized that the ETS family may be crucial to explaining this difference. Normal tissues from the PZ and the TZ of 20 PCA patients were laser microdissected to separate glands from stroma. Two oligo microarrays were performed in order to investigate the variation in ETS family gene expression between the glands and the stroma of the two zones. The ETS members, ELF-3, ELF 5, ERG, ETV-1, ETV-4, ETV-5, ETV-7 and FEV, were found to be differentially expressed. A striking observation was that ERG and ETV-1 were found to be up regulated in the glands of the PZ compared to the TZ, particularly when considering that ERG and ETV-1 fusions account for 50-80% and 20% of PCA occurrences, respectively. These results indicate that the glands and stroma of the two zones display distinct molecular differences and zonal-specific expression of ETS members. Furthermore, ETS members up-regulated in PCA are already overexpressed in the normal PZ, suggesting that these members play a role in the development and progression of PCA. PMID- 22038309 TI - Prophylactic decompression and bone grafting for small asymptomatic osteonecrotic lesions of the femoral head. AB - Core decompression and grafting has been shown to relieve pain and possibly prevent disease progression in patients with symptomatic osteonecrosis (ON) of the hip. However, there is a lack of evidence regarding the management of the asymptomatic hip with femoral head ON. The purpose of this study was to evaluate the outcome of core decompression in the asymptomatic hip with ON. We prospectively followed 37 consecutive patients with MRI confirmed ON of the hips that underwent simultaneous bilateral core decompression and bone grafting. Prior to surgery, only one of the hips was symptomatic, and the main indication for surgical decompression of the asymptomatic side was to prevent disease progression. No hip on the asymptomatic side was staged greater than Steinberg IIB classification. Serial radiographs were followed for evidence of disease progression. Six patients were lost to follow-up prior to two years. The remaining 31 patients were followed for an average of 32.6 months. There were 20 men and 11 women with an average age of 40.6 years. Ten patients with asymptomatic hips at the time of surgical decompression had disease progression requiring THA. The mean time to arthroplasty in this group was 15.1 months. Meanwhile, 13 symptomatic hips at the initial surgery progressed to THA at an average of 12.9 months following core decompression. The proportion of hips requiring conversion to THA was similar between the two groups (p=0.30), and the rate of progression to THA was not significantly faster compared to patients with symptomatic hips who subsequently required THA (p=0.18). Core decompression for asymptomatic ON of the femoral head is unpredictable. Based on our results, asymptomatic ON lesions particularly in the setting of bilateral disease should be closely observed and surgery reserved for when symptoms arise. PMID- 22038310 TI - The effects of femoral derotation osteotomy in cerebral palsy: a kinematic and kinetic study. AB - We attempted to quantify the effects of isolated femoral derotation osteotomies using clinical evaluation and gait analysis (kinematics and kinetics) in patients with cerebral palsy (CP). Twelve children with CP were evaluated before and 10 months after isolated femoral derotation osteotomy, and 15 healthy children were evaluated as controls. There were significant improvements on clinical examination. A better position of the hip and ankle in the transverse plane was evident and significant changes occurred in terms of hip and ankle kinetics after surgery. Improvements in kinematics and hip and ankle power are very important biomechanically. The correction of lever arm dysfunction and more physiological hip and ankle power generation result in an improvement in terms of energy consumption, leading to a more functional and economic gait pattern. PMID- 22038311 TI - The diagnostic accuracy of magnetic resonance imaging and ultrasonography in gluteal tendon tears--a systematic review. AB - Gluteal tendon tears are one of the many pathologies causing pain around the greater trochanter that are often labelled as trochanteric bursitis. We systematically reviewed the peer-reviewed literature to establish the accuracy of magnetic resonance imaging and ultrasonography in the diagnosis of gluteal tendon tears in patients with persistent lateral hip pain or Greater Trochanteric Pain Syndrome (GTPS). 7 studies met the inclusion criteria, comparing either imaging modality with a reference standard of surgical findings. Included studies were assessed for methodological quality using the QUADAS checklist. MRI had sensitivity of 33-100%, specificity of 92-100%, positive predictive value of 71 100% and negative predictive value of 50%. False-positives were common. High signal located superior to the trochanter had a stronger association with tears. Ultrasonography had a sensitivity of 79-100% and positive predictive value of 95 100%. The amount and quality of literature on the subject is limited and further well-designed studies are required to establish the optimum diagnostic strategy in this condition. Ultrasonography may prove to be the investigation of choice, despite requiring a skilled practitioner. The orthopaedic surgeon should liaise with an experienced musculoskeletal radiologist to best investigate and diagnose gluteal tendon tears in the clinical picture of GTPS. PMID- 22038312 TI - Dose verification of IMRT by use of a COMPASS transmission detector. AB - Our purpose in this study was to evaluate the fundamental accuracy of reconstructed dose distributions from the COMPASS system using specific MLC test patterns and complicated IMRT neck plans. The COMPASS-reconstructed dose distributions were compared with those measured with EPID, MapCHECK, and EDR2 film and as well as Monte Carlo-calculated dose profiles with use of square-wave chart patterns of 20-, 10-, and 5-mm gaps and step and pyramid patterns. Additionally, the COMPASS dose distributions for clinical IMRT neck plans were tested. The COMPASS dose profiles were almost in agreement with the Monte Carlo calculated dose profiles and point doses measured with MapCHECK for 20- and 10-mm gap patterns. The dose profile for a 5-mm gap pattern showed a narrow width due to the detector size in the penumbra region. For step and pyramid patterns, COMPASS agreed with MapCHECK and Monte Carlo calculation, except for EDR2 film. The COMPASS and MapCHECK dose distributions agreed with that of a treatment planning system by gamma analysis (criteria; 3 mm/3%). In comparisons of clinical IMRT neck dose distributions, COMPASS was measured with almost the same accuracy as MapCHECK, but slight deviations were found for large IMRT fields. These deviations could be minimized by improvement of the beam model of the COMPASS system. The COMPASS system can be expected to be used for traditional QA methods in clinical routine with the same accuracy as a MapCHECK diode detector. PMID- 22038313 TI - Correction of liver displacement due to irregular respiration for SPECT images obtained using a multiple short-time acquisition with breath-holding technique. AB - Recently, a new method for acquiring single photon emission computed tomography (SPECT) data during breath-holding with a high-speed rotation (HSR-SPECT) technique was applied to hepatic-function scintigraphy. This technique can suppress motion artifact caused by respiration. However, it is challenging to apply this technique to patients with respiratory problems. Our purpose in this study was to analyze projection data and correct liver displacement due to irregular respiration during technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin ((99m)Tc-GSA) liver SPECT scans. We calculated cross-correlation functions (CCFs) for both intra- and inter-projections to correct irregular projections by shifting them in the longitudinal direction enough to maximize the CCFs. We integrated all of the shifted projections and created a synthesis projection which was used to reconstruct SPECT images. To confirm the effectiveness of our method, we did both a phantom study and a clinical retrospective review. In the phantom study, blurring artifacts due to displacement were reduced using our method. Post-processing using our method showed improvements in the normalized mean square error values ranging from 0.18 to 0.06. Furthermore, our method showed no disadvantage or miss-correction if we applied our method to data without displacement. In the clinical review, our method improved the image clarity for patients who could not repeat consistent respiration. In both the phantom simulation and the clinical application, the results showed the usefulness of our method. The efficiency of our method has the potential to reduce the displacement problem caused by respiration and provides excellent matching SPECT/CT fusion images. PMID- 22038314 TI - Multiplexing superparamagnetic beads driven by multi-frequency ratchets. AB - Here, we explore the single particle dynamics of superparamagnetic beads exposed to multifrequency ratchets. Through a combination of theory, simulation, and experiment, we determine the important tuning parameters that can be used to implement multiplexed separation of polydisperse colloidal mixtures. In particular, our results demonstrate that the ratio of driving frequencies controls the transition between open and closed trajectories that allow particles to be transported across a substrate. We also demonstrate that the phase difference between the two frequencies controls not only the direction of motion but also which particles are allowed to move within a polydisperse mixture. These results represent a fundamentally different approach to colloidal separation than the previous methods which are based on controlling transitions between phase locked and phase-slipping regimes, and have a higher degree of multiplexing capabilities that can benefit the fields of biological separation and sensing as well as provide crucial insights into general ratchet behavior. PMID- 22038315 TI - Acute effects of a single warm-water bath on serum adiponectin and leptin levels in healthy men: a pilot study. AB - To preliminarily assess the acute effects of a single warm-water bath (WWB) on serum adipokine activity, we measured serum adiponectin, leptin and other metabolic profiles before, immediately after and 30 minutes after WWB in seven healthy male volunteers (mean age, 39.7 +/- 6.0 years; mean body mass index, 21.6 +/- 1.8 kg/m(2)). The subjects were immersed in tap water at 41 degrees C for 10 minutes. Two weeks later, the same subjects underwent a single WWB with a bath additive that included inorganic salts and carbon dioxide (WWB with ISCO(2)) by the same protocol as for the first WWB. Leptin levels significantly increased immediately after WWB with tap water and ISCO(2) (both P < 0.05), and remained significantly higher than those at baseline even 30 minutes after WWB with tap water (P < 0.05). Adiponectin levels showed a slight, but not significant, increase both immediately after and 30 minutes after WWB with tap water or ISCO(2). Some parameters, such as serum total cholesterol, red blood cell count, hemoglobin and hematocrit significantly increased immediately after WWB with tap water or ISCO(2) (all P < 0.05), but they all returned to the baseline levels 30 minutes after bathing under both conditions. The sublingual temperature rose significantly after 10 minutes of WWB with tap water (0.96 +/- 0.16 degrees C relative to baseline, P < 0.01) and after the same duration of WWB with ISCO(2) (1.24 +/- 0.34 degrees C relative to baseline, P < 0.01). These findings suggest that a single WWB at 41 degrees C for 10 minutes may modulate leptin and adiponectin profiles in healthy men. PMID- 22038316 TI - The role of resistin in Behcet's disease: a Turkish experiment. AB - The objective of this study was to assess the role of resistin, a proinflammatory cytokine potentially involved in Behcet's disease (BD), and to determine its relationship with tumor necrosis factor alpha (TNF-alpha), another important inflammatory cytokine known to be involved in BD. Forty-five persons diagnosed with BD were enrolled into this study, 25 of whom were being followed or had recently been diagnosed with clinically active BD, whereas the remaining 20 were previously diagnosed and had clinically inactive BD for the previous 3 months. Thirty persons were recruited as a healthy control group. Patients' C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), resistin, and TNF-alpha levels were determined with enzyme-linked immunosorbent assay (ELISA). Resistin and TNF-alpha levels were significantly higher in patients with BD (p < 0.05 and p < 0.05) than in the control group. The major interest of this study was to investigate the role of resistin in patients with BD. An elevated resistin level was associated with activation of BD. Elevated TNF-alpha and resistin levels could be determined simultaneously, and the presence of these two cytokines together suggests that resistin plays an important role in the pathogenesis and activation of BD. PMID- 22038317 TI - The role of biologics in treatment of ANCA-associated vasculitis. AB - The vast majority of patients with anti-neutrophil cytoplasmic autoantibody associated vasculitis (AAV) who receive conventional treatment with glucocorticoids and cyclophosphamide experience frequent relapses and treatment related side-effects. Increasing knowledge of the pathogenesis of AAV has permitted the development of targeted therapies against tumour necrosis factor (TNF)-alpha and T and B lymphocytes. Therapy with TNF-alpha blocking drugs has so far proved disappointing, and this approach is not recommended. B cell depletion using rituximab is effective for remission induction, especially in refractory patients. The long-term side-effects and the best method of using rituximab to maintain remission are still to be determined. PMID- 22038319 TI - Bullying and peer victimisation in adolescent girls with Attention Deficit/Hyperactivity Disorder. AB - Emerging evidence suggests that adolescent girls with Attention Deficit/Hyperactivity Disorder (ADHD) are more socially impaired compared with their peers; however, research has yet to elucidate the nature of this impairment. We investigated overt (e.g., physical, such as hitting or kicking or verbal, such as teasing and taunting) and relational (e.g., social manipulation, such as social exclusion) bullying and victimisation in adolescent girls with and without ADHD. Adolescent girls (mean age = 15.11) with (n = 22) and without (n = 20) ADHD and their primary caregivers completed measures of overt/relational bullying and victimisation and social impairment. Adolescent girls with ADHD experienced more social problems and more relational and overt victimisation than adolescent girls without ADHD. Although adolescent girls with ADHD engaged in more overt and relational bullying than adolescent girls without ADHD, this difference was not statistically significant. Oppositional Defiant Disorder symptoms appeared to be more strongly related to bullying behaviour, while victimisation appeared to be more strongly related to ADHD. PMID- 22038320 TI - National park development in China: conservation or commercialization? AB - The rapid development of parks and ecotourism in China has attracted worldwide attention, not only for the beauty of the landscape that the parks are protecting but also for their abundant and often unique biodiversity. However, in some areas, the development of ecotourism has actually led to the degradation of local ecological, economic, and social systems. Using National Forest Parks for demonstration, this article analyzes the current political, institutional, legal, environmental, and economic issues concerning National Parks in China, and examines their potential future development. Although the intention of National Park systems in China is to raise environmental quality, and to protect biodiversity and social livelihoods, their success has varied. Future success will be measured by their capacity to reduce poverty, to promote long-term rehabilitation of wildlife habitats, and to simultaneously protect Chinese culture and biodiversity. PMID- 22038321 TI - Luminescent lanthanide-binding peptides: sensitising the excited states of Eu(III) and Tb(III) with a 1,8-naphthalimide-based antenna. AB - The investigation into the luminescence properties of a lanthanide-binding peptide, derived from the Ca-binding loop of the parvalbumin, and modified by incorporating a 1,8-naphthalimide (Naph) chromophore at the N-terminus is described. Here, the Naph is used as a sensitising antenna, which can be excited at lower energy than classical aromatic amino acids, such as tryptophan (the dodecapeptide of which was also synthesised and studied herein). The syntheses of the Naph antenna, its solid phase incorporation into the dodecapeptide, and the NMR investigation into the formation of the corresponding lanthanide complexes in solution is presented. We also show that this Naph antenna can be successfully employed to sensitize the excited states of both europium and terbium ions, the results of which was used to determined the stability constants of their formation complexes, and we demonstrated that our peptide 'loop' can selectively bind these lanthanide ions over Ca(II). PMID- 22038322 TI - Sleep and cardiovascular regulation. AB - Normal sleep has a profound effect on the cardiovascular system, reducing cardiovascular activity throughout non-rapid eye movement sleep; changes that are modified and augmented by circadian system influence. There is also evidence that sleep-initiated changes in autonomic balance may in turn modify the development of sleep within a night, particularly the development of slow wave sleep. It is assumed that the cardiovascular changes that accompany sleep reflect a functional aspect of sleep, although the precise functional role has not been agreed upon. Nevertheless, there is good evidence that the cardiovascular changes that occur during normal sleep are beneficial for the cardiovascular system. Arousals from sleep, which are common even in normal sleep, are associated with a surge in activity in cardiorespiratory systems, with marked effects on the sleep-related pattern of cardiovascular activity when they occur frequently. Despite the importance of this aspect of sleep, controversy remains as to both the nature of the activation response and the circumstances under which it is elicited. The concept that sleep-related changes in cardiovascular activity are beneficial leads to the corollary that sleep disturbance would result in adverse cardiovascular consequences. While there is strong empirical evidence for such a relationship, it remains unclear whether this is a direct effect or, as has been suggested recently, the effect of disturbed sleep is mediated via stress-related modification of neuroendocrine systems. PMID- 22038324 TI - A 2,2',6,6'-tetraphosphinobiphenyl. AB - The first example of a 2,2',6,6'-tetraphosphinobiphenyl was prepared and used as a ligand in a dinuclear palladium(II) complex. The close proximity of the two complex fragments induces a coupling pathway allowing the allosteric communication between the two palladium complex fragments. PMID- 22038323 TI - Umbellulone modulates TRP channels. AB - Inhalation of umbellulone (UMB), the offensive principle of the so-called "headache tree" (California bay laurel, Umbellularia californica Nutt.), causes a painful cold sensation. We therefore studied the action of UMB and some derivatives devoid of thiol-trapping properties on the "cold" transient receptor potential cation channels TRPA1 and TRPM8. UMB activated TRPA1 in a dose dependent manner that was attenuated by cysteine-to-serine isosteric mutation in TRPA1 (C622S), while channel block was observed at higher concentration. However, although activation by mustard oil was completely prevented in these mutants, UMB still retained activating properties, indicating that it acts on TRPA1 only as a partial electrophilic agonist. UMB also activated TRPM8, but to a lower extent than TRPA1. Removing Michael acceptor properties of UMB (reduction or nucleophilic trapping) was detrimental for the activation of TRPA1, but increased the blocking potency. This was, however, attenuated by acetylation of the hydroxylated analogs. All UMB derivatives, except the acetylated derivatives, were also TRPM8 activators. They acted, however, in a bimodal manner, inhibiting the channel more potently than UMB, and with tetrahydro-UMB being the most potent TRPM8 activator. In conclusion, UMB is a bimodal activator of TRPA1 and a weak activator of TRPM8. Non-electrophilic derivatives of UMB are better TRPM8 activators than the natural product and also potent blockers of this channel as well as of TRPA1. The lack of effects of the acetylated UMB derivatives suggests that steric hindrance may prevent access to the recognition site for the bicyclic monoterpene pharmacophore on TRPA1 and TRPM8. PMID- 22038325 TI - Phenolic compounds in wheat grain cultivars. AB - Three hydroxybenzoic acids: p-hydroxybenzoic acid, vanillic acid and syringic acid; six hydroxycinnamic acids: p-coumaric acid, ferulic acid and four ferulic acid derivatives and a flavonoid (apigenin) were identified and quantified in 34 accessions corresponding to 19 cultivars of wheat applying HPLC coupled to diode array detector. Considerable differences between the wheat cultivars were observed in the phenolic contents. Some cultivars (Colorado, Del Pais, Barbilla, Jallado, Raspinegro Canario and Plaganudo) could be selected according to the high levels of phenolic compounds. Ferulic acid was the major phenolic acid compound followed by syringic and p-hydroxybenzoic acids. The proportion of ferulic acid present as dimeric forms ranged from 4.2 to 8.6% across all of the wheat cultivars analyzed. Apigenin, p-hydroxybenzoic and syringic acids did not show significant correlations. Many correlations between the determined hydroxycinnamic acids were observed. The ferulic acid and all the ferulic acid derivatives showed highly significant correlations, suggesting that the concentrations of diferulic acids depend on the concentration of ferulic acid. PMID- 22038326 TI - Neural basis of singing in crickets: central pattern generation in abdominal ganglia. AB - The neural mechanisms underlying cricket singing behavior have been the focus of several studies, but the central pattern generator (CPG) for singing has not been localized conclusively. To test if the abdominal ganglia contribute to the singing motor pattern and to analyze if parts of the singing CPG are located in these ganglia, we systematically truncated the abdominal nerve cord of fictively singing crickets while recording the singing motor pattern from a front-wing nerve. Severing the connectives anywhere between terminal ganglion and abdominal ganglion A3 did not preclude singing, although the motor pattern became more variable and failure-prone as more ganglia were disconnected. Singing terminated immediately and permanently after transecting the connectives between the metathoracic ganglion complex and the first unfused abdominal ganglion A3. The contribution of abdominal ganglia for singing pattern generation was confirmed by intracellular interneuron recordings and current injections. During fictive singing, an ascending interneuron with its soma and dendrite in A3 depolarized rhythmically. It spiked 10 ms before the wing-opener activity and hyperpolarized in phase with the wing-closer activity. Depolarizing current injection elicited rhythmic membrane potential oscillations and spike bursts that elicited additional syllables and reliably reset the ongoing chirp rhythm. Our results disclose that the abdominal ganglion A3 is directly involved in generating the singing motor pattern, whereas the more posterior ganglia seem to provide only stabilizing feedback to the CPG circuit. Localizing the singing CPG in the anterior abdominal neuromeres now allows analyzing its circuitry at the level of identified interneurons in subsequent studies. PMID- 22038327 TI - Extending the latent variable model for extra correlated longitudinal dichotomous responses. AB - Since generalized nonlinear mixed-effects modeling methodology of ordered categorical data became available in the pharmacokinetic/pharmacodynamic (PK/PD) literature over a decade ago, pharmacometricians have been increasingly performing exposure-response analyses of such data to inform drug development. Also, as experiences with and scrutiny of these data have increased, pharmacometricians have noted fewer transitions (or greater correlations) between response values than predicted by the model. In this paper, we build on the latent variable (LV) approach, which is convenient for incorporating pharmacological concepts such as pharmacodynamic onset of drug effect, and present a PK/PD methodology which we term the multivariate latent variable (MLV) approach. This approach uses correlations between the latent residuals (LR) to address extra correlation or a fewer number of transitions, relative to if the LR were independent. Four approximation methods for handling dichotomous MLV data are formulated and then evaluated for accuracy and computation time using simulation studies. Some analytical results for models linear in the subject specific random effects are also presented, and these provide insight into modeling such repeated measures data. Also, a case study previously analyzed using the LV approach is revisited using one of the MLV approximation methods and the results are discussed. Overall, consideration of the simulation and analytical results lead us to some conclusions we feel are applicable to many of the models and situations frequently encountered in analysis of such data: the MLV approach is a flexible method that can handle many different extra correlated data structures and therefore can more accurately predict the number of transitions between response values; incorrect modeling of the population covariances by implementing an LV model when extra correlation exists is not likely to (and in many cases does not) influence accuracy of the population (marginal) mean predictions; adequate prediction of the population mean probabilities achieves adequate predictions of the population variances, regardless of the correct specification of the population covariances--that is, if the LV model accurately predicts the means in the presence of extra correlation, it will accurately predict the variances; the between subject random effects component to the model describe the marginal covariances in responses- not the marginal variances as with continuous-type data. From these conclusions we make a general statement that it may not be necessary to model the extra correlation in every case using the MLV model, which requires technical implementation with currently available commercially or publically available software. The LV model may be sufficient for answering many of the typical questions arising during drug development. The MLV approach should be considered however if prediction or simulation of individual level data is an objective of the analysis. PMID- 22038328 TI - Highly-integrated lab-on-chip system for point-of-care multiparameter analysis. AB - A novel innovative approach towards a marketable lab-on-chip system for point-of care in vitro diagnostics is reported. In a consortium of seven Fraunhofer Institutes a lab-on-chip system called "Fraunhofer ivD-platform" has been established which opens up the possibility for an on-site analysis at low costs. The system features a high degree of modularity and integration. Modularity allows the adaption of common and established assay types of various formats. Integration lets the system move from the laboratory to the point-of-need. By making use of the microarray format the lab-on-chip system also addresses new trends in biomedicine. Research topics such as personalized medicine or companion diagnostics show that multiparameter analyses are an added value for diagnostics, therapy as well as therapy control. These goals are addressed with a low-cost and self-contained cartridge, since reagents, microfluidic actuators and various sensors are integrated within the cartridge. In combination with a fully automated instrumentation (read-out and processing unit) a diagnostic assay can be performed in about 15 min. Via a user-friendly interface the read-out unit itself performs the assay protocol, data acquisition and data analysis. So far, example assays for nucleic acids (detection of different pathogens) and protein markers (such as CRP and PSA) have been established using an electrochemical read out based on redoxcycling or an optical read-out based on total internal reflectance fluorescence (TIRF). It could be shown that the assay performance within the cartridge is similar to that found for the same assay in a microtiter plate. Furthermore, recent developments are the integration of sample preparation and polymerase chain reaction (PCR) on-chip. Hence, the instrument is capable of providing heating-and-cooling cycles necessary for DNA-amplification. In addition to scientific aspects also the production of such a lab-on-chip system was part of the development since this heavily affects the success of a later market launch. In summary, the Fraunhofer ivD-platform covers the whole value chain ranging from microfluidics, material and polymer sciences, assay and sensor development to the production and assembly design. In this consortium the gap between diagnostic needs and available technologies can be closed. PMID- 22038329 TI - Diffusion-weighted MRI: a useful technique to discriminate benign versus malignant ovarian surface epithelial tumors with solid and cystic components. AB - PURPOSE: To evaluate differences in apparent diffusion coefficient (ADC) values for the solid component of benign and malignant ovarian surface epithelial tumors with the goal of differentiating benign versus malignant ovarian tumors preoperatively. MATERIALS AND METHODS: A total of 127 patients with 131 pelvic masses identified by ultrasound between January 2006 and January 2011 were enrolled in this study. 46 patients were diagnosed with benign tumors, and 85 patients were diagnosed with malignant pathologies. For all of the patients, routine spin-echo MRI and diffusion-weighted imaging were performed. ADC values were determined for all of the masses, and the mean ADC values for the benign and malignant tumors were analyzed using Student's t test. A P value <0.05 was considered statistically significant. RESULTS: Mean ADC values associated with malignant ovarian surface epithelial tumors were significantly lower than the mean ADC values of the benign tumors. In addition, the range of ADC values associated with a 95% confidence interval did not overlap between the two groups. ROC analysis indicated that a cutoff ADC value of 1.25 * 10(-3) mm(2)/s was associated with 90.1% sensitivity and 89.9% specificity. CONCLUSION: ADC values determined from 1.5 T MR DWI of benign and malignant ovarian masses were found to be significantly different. PMID- 22038330 TI - High-risk prostate cancer: value of multi-modality 3T MRI-guided biopsies after previous negative biopsies. AB - Transrectal ultrasound-guided biopsy is the gold standard for prostate cancer detection. The latter detection rates of random systematic TRUS-guided biopsy do not exceed 44%. As a consequence other biopsy methods have been explored. One of these methods is MR-guided biopsy (MRGB), which revealed detection rates of 38 59% after previous negative TRUSGB sessions. For this reason MRGB will probably become more and more applied in daily practice. PMID- 22038331 TI - Uneven haustra on CT colonography: a clue for the detection of transperitoneal invasion from gastric cancer. AB - Two patients with gastric carcinoma underwent CT colonography (CTC) for preoperative work-up. Although no obvious peritoneal nodules were seen on axial CT images, colonic wall deformities were noted on three-dimensional (3D) air images. Multiplanar-reformatted images revealed corresponding colonic wall thickening at the deformities, and in addition, dense cordlike structures connecting the primary gastric cancer and colonic wall thickening were also observed. In one patient, cordlike indurations consistent with peritoneal invasion were found to connect the primary gastric cancer, gastrocolic ligament, and transverse mesocolon during exploratory surgery, and in the other, colonic scars consistent with peritoneal invasion after chemotherapy were observed. These observations suggest that CTC could be of potential use for the differentiation of transperitoneal colonic invasion and gastric cancer. PMID- 22038333 TI - Global solutions to the challenges of setting up and managing a stem cell laboratory. PMID- 22038332 TI - Ca2+ activated K channels-new tools to induce cardiac commitment from pluripotent stem cells in mice and men. PMID- 22038334 TI - Cost comparison of online haemodiafiltration with high-flux haemodialysis. AB - INTRODUCTION: Haemodiafiltration increases convective clearances, and online haemodiafiltration (OL-HDF) was introduced to reduce costs of producing large volumes of ultrapure water. Previous reports have suggested that OL-HDF may be a cost-saving therapy by reducing recombinant human erythropoietin requirements and those for other medications. We therefore costed OL-HDF with high-flux haemodialysis. METHODS: Thirty-four patients dialysing (Tue/Thu/Sat) switched to OL-HDF, and 44 dialysing (Mon/Wed/Fri) remained on high-flux haemodialysis (HD) in a satellite dialysis centre. They were then prospectively followed for 12 months. RESULTS: Depending upon whether blood lines with a cuvette for measuring relative blood volume were used, OL-HDF was either slightly more expensive per session, by L1.16, as the cost of the reinfusion line outweighed any potential savings in 0.9% saline usage, or cheaper by L0.78 if standard blood lines were used. Although there were initial increased costs for more frequent testing of dialysis machine water quality. It could be argued that similar water quality is required for high-flux haemodialysis using dialysers with increased internal filtration. There was no cost saving in terms of recombinant human erythropoietin prescription, but whereas weekly phosphate binder costs increased in the high flux haemodialysis cohort from L3.8 (range 1.9-14.8) to L5.0 (range 1.9-21.3; p=0.01), costs did not change with OL-HDF (L3.8, range 1.9-11.9). CONCLUSION: Depending upon the choice of blood lines, OL-HDF was either a slightly more expensive or a cheaper treatment per session compared with high-flux haemodialysis in our centre. Treatment with OL-HDF also led to modest cost savings on phosphate binders. PMID- 22038335 TI - C-reactive protein as a predictor of cardiovascular events in elderly patients with chronic kidney disease. AB - BACKGROUND: Few studies have evaluated the relationship between high-sensitivity C-reactive protein (hs-CRP) and vascular events in the elderly with chronic kidney disease (CKD). METHODS: The association of hs-CRP with vascular events was examined according to CKD status in 3,166 participants of the Intervention Project on Cerebrovascular Diseases and Dementia in the Community of Ebersberg, Bavaria (INVADE study). CKD was defined as a creatinine clearance <60 ml/min estimated by the Cockcroft-Gault formula. hs-CRP was used as a binary variable > or <2.1 mg/L (median value). Vascular events were defined as a composite of myocardial infarction, stroke and vascular death. RESULTS: After 4 years of follow-up, 204 participants (6.4%) experienced a major cardiovascular event. High hs-CRP levels and CKD at baseline were associated with a greater risk of vascular events. Compared with patients with low hs-CRP and non-CKD, the adjusted hazard ratio (95% confidence interval) for vascular events was 1.42 (1.11-2.21) for low hs-CRP and CKD, 1.57 (1.21-2.34) for high hs-CRP and non-CKD and 1.93 (1.45-2.89) for high hs-CRP and CKD. CONCLUSIONS: These results suggest that high hs-CRP levels provide prognostic information in patients with CKD. PMID- 22038336 TI - Effect of early conversion from CNI to sirolimus on outcomes in kidney transplant recipients with allograft dysfunction. AB - BACKGROUND: Studies evaluating the effect of conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) in renal transplant recipients (RTRs) have shown conflicting results, and only few short-term uncontrolled studies are available in patients with chronic allograft dysfunction. This is the first controlled study to evaluate long-term survival and both renal and cardiac outcomes in nondiabetic RTRs with allograft dysfunction who were converted from CNI to SRL. METHODS: We evaluated 13 RTRs with biopsy-proven allograft dysfunction who underwent early conversion from CNI to SRL, and 26 controls with normal graft function taking CNI. All continued both steroids and mycophenolate mofetil. SRL was titrated to trough levels of 4-8 ng/mL. Outcome measures included 3-year event-free survival, acute rejection rate and 3-year changes in Modification of Diet in Renal Disease (MDRD) Study equation estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMi) as assessed by echocardiography. RESULTS: Compared with controls, patients on SRL showed better 3-year event-free survival (p=0.024; log-rank test), significant eGFR increase (+5.5 +/- 8.9 vs, -6.4 +/- 14.7 ml/min per 1.73 m2, p=0.011), LVMi regression ( 9.0 +/- 7.6 g/m(2.7) vs. 1.0 +/- 10.1 g/m(2.7), p=0.0038) and similar acute rejection rate. Three-year change in eGFR was the only significant predictor of event-free survival by Cox regression analysis (hazard ratio = 0.96; 95% confidence interval, 0.93-0.99; p=0.017), whereas SRL was the strongest predictor of both eGFR increase (beta coefficient, 0.342; p=0.01) and LVM reduction (beta coefficient, -0.609; p=0.0001) by multivariate regression analysis. CONCLUSIONS: Conversion from CNI to SRL in RTRs with allograft dysfunction proved to be associated with better survival, improved renal graft function and regression of cardiac hypertrophy. PMID- 22038337 TI - A population-based approach for the definition of chronic kidney disease: the CKD Prognosis Consortium. AB - INTRODUCTION: The Kidney Disease: Improving Global Outcomes (KDIGO) foundation promoted the establishment of the Chronic Kidney Disease (CKD) Prognosis Consortium to meta-analyze the association of estimated glomerular filtration rate (eGFR) and albuminuria with incidence of various outcomes in samples of general populations from all over the world. METHODS: Variables in meta-analysis included eGFR by the Modification of Diet in Renal Disease (MDRD) Study equation, the urinary albumin to creatinine ratio (uACR) as index of albuminuria, together with proteinuria at dipstick urinalysis and classical markers of cardiovascular risk. Overall, 105,872 participants had uACR measurements, and 1,128,310 participants had dipstick measurements. RESULTS: The association with mortality was continuous over the whole range of uACR/proteinuria and J-shaped for eGFR which was associated with an excess risk for values <75 and >=120 ml/min per 1.73 m2. Results were similar for the association of eGFR or uACR/proteinuria with renal failure. The associations of eGFR and uACR/proteinuria with death or renal failure were independent of each other. Findings were consistent across population samples from North America, Asia, Oceania and Europe, as well as in individuals with age <65 years and individuals with age >=65 years. CONCLUSIONS: Data support the threshold of 60 ml/min for CKD definition but suggest that eGFR in the range 60-74 ml/min could represent the early stages of CKD. This first set of results of the CKD Prognosis Consortium represents an important step in the evidence-based definition of CKD. Conclusions should be reevaluated with eGFR calculation by equations less biased for normal-high eGFR. PMID- 22038338 TI - Internet training to respond to aggressive resident behaviors. AB - PURPOSE: This research evaluated an individualized Internet training designed to teach nurse aides (NAs) strategies to prevent or, if necessary, react to resident aggression in ways that are safe for the resident as well as the caregiver. DESIGN AND METHODS: A randomized treatment and control design was implemented, with baseline, 1-, and 2-month assessments for 158 NAs. The training involved 2 weekly visits. The Internet intervention was a behaviorally focused and video based training that included content on skills for safely dealing with physical aggression. Measures included video situation testing and assessment of psychosocial constructs associated with behavior change. RESULTS: Analysis of covariance showed positive results for knowledge, attitudes, self-efficacy, and empathy, with medium-large effect sizes maintained after 2 months. The training was well received by participants. IMPLICATIONS: Internet training is a viable approach to shape appropriate NA reactions to aggressive resident behaviors. This format has future potential because it offers fidelity of presentation and automated documentation, with minimal supervision. PMID- 22038339 TI - International spotlight: Israel. AB - The State of Israel provides significant opportunities to study social processes that can enhance our understanding of the aging experience. It has high life expectancy and rapid growth of its older population. With an older cohort that is composed largely of former immigrants and includes a minority Arab population, Israel provides much diversity for gerontological study. Among the unique issues facing older Israelis are the aging of Holocaust survivors, modernization in the Arab sector, and privatization in the kibbutzim. New legislation related to pensions and universal health care is expected to affect aging processes. The development of "supportive communities" offers a new service model. The article notes 2 longitudinal studies of importance-the Israeli component of the Survey of Health, Ageing, and Retirement in Europe and the Jerusalem Longitudinal Cohort Study. PMID- 22038340 TI - Cancer mortality among atomic bomb survivors exposed as children. AB - OBJECTIVES: To compare cancer mortality among A-bomb survivors exposed as children with cancer mortality among an unexposed control group (the entire population of Japan, JPCG). METHODS: The subjects were the Hiroshima and Nagasaki A-bomb survivor groups (0-14 years of age in 1945) reported in life span study report 12 (follow-up years were from 1950 to 1990), and a control group consisting of the JPCG. We estimated the expected number of deaths due to all causes and cancers of various causes among the exposed survivors who died in the follow-up interval, if they had died with the same mortality as the JPCG (0-14 years of age in 1945). We calculated the standardized mortality ratio (SMR) of A bomb survivors in comparison with the JPCG. RESULTS: SMRs were significantly higher in exposed boys overall for all deaths, all cancers, leukemia, and liver cancer, and for exposed girls overall for all cancers, solid cancers, liver cancer, and breast cancer. In boys, SMRs were significantly higher for all deaths and liver cancer even in those exposed to very low doses, and for all cancers, solid cancers, and liver cancer in those exposed to low doses. In girls, SMRs were significantly higher for liver cancer and uterine cancer in those exposed to low doses, and for leukemia, solid cancers, stomach cancer, and breast cancer in those exposed to high doses. CONCLUSIONS: We calculated the SMRs for the A-bomb survivors versus JPCG in childhood and compared them with a true non-exposed group. A notable result was that SMRs in boys exposed to low doses were significantly higher for solid cancer. PMID- 22038341 TI - Advantages of statistical analysis of giant vesicle flickering for bending elasticity measurements. AB - We show how to greatly improve precision when determining bending elasticity of giant unilamellar vesicles. Taking advantage of the well-known quasi-spherical model of liposome flickering, we analyze the full probability distributions of the configurational fluctuations instead of limiting the analysis to the second moment measurements only as usually done in previously published works. This leads to objective criteria to reject vesicles that do not behave according to the model. As a result, the confidence in the bending elasticity determination of individual vesicles that fit the model is improved and, consequently, the reproducibility of this measurement for a given membrane system. This approach uncovers new possibilities for bending elasticity studies like detection of minute influences by solutes in the buffer or into the membrane. In the same way, we are now able to detect the inhomogeneous behavior of giant vesicle systems such as the hazardous production of peroxide in bilayers containing fluorescent dyes. PMID- 22038342 TI - HepG2 cells infected with Klebsiella pneumoniae show DNA laddering at apoptotic and necrotic stages. AB - Virulent Klebasiella pneumoniae (KP) inflicts severe liver abscesses in infected patients. This study investigated how the bacterial infection affected cell survival at the molecular level, in a cultured cell model. A strain of KP highly virulent in mice was isolated from a patient with liver abscess, and was used to infect HepG2 cells. The infected cells were examined for their viability, DNA fragmentation, and proteins involved in apoptosis or necrosis. We found that the infection decreased the viability of HepG2 cells at 4 hours (h) to 12 h post infection (pi). DNA ladders appeared 6-16 h pi and flow cytometry analysis showed apoptosis at 3-5 h pi, secondary necrosis at 6-9 h pi and primary necrosis at 8-9 h pi. Cleavages of Caspase 7, Caspase 9, alpha-Fodrin, and PARP were evident at 2 4 h pi. At 7 h pi, we observed the following: increased nuclear AIF, the release from mitochondria of cytosolic Apaf-1 and Cyt c, increased DFF40 expression, decreased DFF45, decreased BcL-xL and the release of Endo G from mitochondria to nucleus. Cellular ATP concentration decreased at 4-8 h pi, accompanied by increased Calpain-2 expression. In summary, infected HepG2 cells underwent apoptosis early after infection and progressed to secondary necrosis and primary necrosis. Nuclear fragmentation corresponded to Caspase 7 activation and the appearance of Endo G and DFF40 in the nucleus, with a concomitant decrease in DFF45. Mitochondrial release of Cyt c together with activation of Caspase 9 and Apaf-1 in cytosol was also observed. Early-hour cleavage of poly(ATP-ribose) polymerase (PARP) followed by the later activation of PARP corresponded to the appearance of DNA laddering, and the depletion of cellular ATP was associated with the appearance of necrosis. PMID- 22038343 TI - Prevalence and clinical correlates of tic disorders in a community sample of school-age children. AB - To examine the prevalence, clinical characteristics and course of children with tics identified in a community sample. This was a three-stage study. At the age of 9 to 11, parents of 8,244 children born at Aarhus University Hospital Skejby between January 1990 and April 1992 were invited to complete a screening questionnaire about tics. One year later participating parents completed the Strengths and Difficulties Questionnaire (SDQ). From December 2004 to June 2005, when the cohort was 13-15 years of age, parents of the children who screened positive for tics were interviewed in detail about tic disorders. The prevalence of Tourette Syndrome (TS) was 0.6 and 0.6% of chronic motor tics (CMT). Approximately one-third of those with a chronic tic disorder [CTD (TS and CMT)] reported remission of tics by age 13-15. On the parent-rated SDQ children with a CTD were five times more likely (OR = 5.0, 95% CI = 2.6-9.2) to fall into the clinical range of hyperactivity, twice as likely (OR = 2.2, 95% CI = 2.1-7.5) to exhibit disruptive and defiant behavior and over four times more likely to have emotional difficulties (OR = 4.7, 95% CI = 2.5-8.6) compared to children without tic disorders. Children with hyperactivity and CTD were more impaired than subjects with CTD only. Children with CTD and hyperactivity show greater symptom severity across several domains of behavior and overall impairment. In the absence of hyperactivity, children with CTD are at increased risk for emotional difficulties, but not disruptive behavior problems. PMID- 22038344 TI - "Better the devil you know": a preliminary study of the differential modulating effects of reputation on reward processing for boys with and without externalizing behavior problems. AB - Very little is known about the neurobiological correlates of reward processing during social decision-making in the developing brain and whether prior social and moral information (reputations) modulates reward responses in youth as has been demonstrated in adults. Moreover, although externalizing behavior problems in youth are associated with deficits in reward processing and social cognition, a real-life social interaction paradigm using functional neuroimaging (fMRI) has not yet been applied to probe reward processing in such youth. Functional neuroimaging was used to examine the neural correlates of reward-related decision making during a trust task in two samples of age-matched 11 to 16-year-old boys: with (n = 10) and without (n = 10) externalizing behavior problems. The task required subjects to decide whether to share or keep monetary rewards from partners they themselves identified during a real-life peer sociometric procedure as interpersonally aggressive or kind (vs. neutral). Results supported the notion that prior social and moral information (reputations) modulated reward responses in the adolescent brain. Moreover, boys with externalizing problems showed differential activation in the bilateral insula during the decision phase of the game as well as the caudate and anterior insula during the outcome phase of the game. Similar activation in adolescents in response to reward related stimuli as found in adults suggests some developmental continuity in corticostriatal circuits. Group differences are interpreted with caution given the small group sizes in the current study. Notwithstanding this limitation, the study provides preliminary evidence for anomalous reward responses in boys with externalizing behavior problems, thereby providing a possible biological correlate of well established social-cognitive and reward-related theories of externalizing behavior disorders. PMID- 22038345 TI - The cross-talk between ROS and p38MAPKalpha in the Ex Vivo expanded human umbilical cord blood CD133(+) cells. AB - This study investigated the correlation between and compared the effects of reactive oxygen species (ROS) and p38 mitogen-activated protein kinase alpha (p38MAPKalpha) in the ex vivo expanded umbilical cord blood (hUCB) CD133(+) cells. hUCB CD133(+) cells were cultured in the hematopoietic stem cells (HSCs) culture medium with N-acetylcysteine (NAC, an anti-oxidant), p38MAPKalpha specific inhibitor (SB203580) or their combination. The levels of ROS and expression of phosphorylated p38MAPKalpha (p-p38) in CD133(+) cells were flow cytometrically detected. The efficacy of ex vivo expansion was evaluated by the density of CD133(+) cell sub-group colony-forming cells (CFC) and cobblestone area-forming cells (CAFC) assay. Our results showed decreased ROS levels in NAC, SB203580, and their combination treatment groups were almost 37%, 48%, and 85%, respectively. Furthermore, SB203580 abrogated the activation of p38MAPKalpha more obviously than NAC. Moreover, the CD133(+) cells in SB203580 treatment group had a 21.93+/-1.36-fold increase, and 14.50+/-1.19-fold increase in NAC treatment group, but only 10.13+/-0.57-fold increase in control group. In addition, SB203580 treatment led a higher level increase in the number of CFU and CAFC than NAC did. These findings suggested that, in expanded CD133(+) cells, ROS activates p38MAPKalpha, which, in turn, induces ROS production, and p38MAPKalpha might be the most suitable regulator in ROS-p38MAPKalpha pathway for the promotion of HSCs ex vivo expansion. PMID- 22038346 TI - P-450-dependent epoxygenase pathway of arachidonic acid is involved in myeloma induced angiogenesis of endothelial cells. AB - P-450-dependent epoxygenase pathway of arachidonic acid and the products of epoxyeicosatrienoic acids (EETs) have been demonstrated to be involved in angiogenesis and tumor progression. This study examined the expression of EETs and the role of the pathway in the angiogenesis of multiple myeloma (MM). MM cell lines of U266 and RPMI8226 were cultured, and the EETs levels (11, 12-EET and 14, 15-EET) in the supernatant were determined by ELISA. Human umbilical vein endothelial cells (HUVECs) were cultured and used for analysis of the angiogenesis activity of the two MM cell lines, which was examined both in vitro and in vivo by employing MTT, chemotaxis, tube formation and matrigel plug assays. 11, 12-EET and 14, 15-EET were found in the supernatant of the cultured MM cells. The levels of the two EETs in the supernatant of U266 cells were significantly higher than those in the RPMI8226 cell supernatant (P<0.05), and the levels paralleled the respective angiogenesis activity of the two different MM cell lines. 17-octadecynoic acid (17-ODYA), as a specific inhibitor of P450 enzyme, suppressed HUVECs proliferation and tube formation induced by MM cells. Furthermore, 17-ODYA decreased the EET levels in the supernatant of MM cells. These results suggest that EETs may play an important role in the angiogenesis of MM, and the inhibitor 17-ODYA suppresses this effect. PMID- 22038347 TI - The elevated expression of osteopontin and NF-kappaB in human aortic aneurysms and its implication. AB - The expression and significance of osteopontin (OPN) and NF-kappaB in patients with thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) were investigated. Thirteen TAA specimens, 20 AAA specimens and 6 normal aortic specimens were collected. The expression of OPN, nuclear factor-kappaB P65 (NF kappaB P65), urokinase plasminogen activator (uPA), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were detected by using immunohistochemistry and Western blotting was employed to determine the expression of OPN and NF-kappaB P65. Immunohistochemical results showed that the expression of OPN, NF-kappaB P65, uPA, MMP-2 and MMP-9 was positive in all TAA and AAA specimens and negative in normal specimens, with the difference being statistically significant (P<0.05). There was no difference in the expression between TAA and AAA specimens (P>0.05). Correlation analysis revealed that there existed a positive correlation between the expression of OPN and that of NF kappaB P65, uPA, MMP-2 and MMP-9 and between the expression of NF-kappaB P65 and that of uPA, MMP-2, MMP-9 (P<0.05). Western blotting demonstrated that OPN and NF kappaB P65 were positive in AAA and TAA specimens, and negative in normal specimens with the differences being statistically significant (P<0.05). There were no statistically significant differences in the expression of OPN and NF kappaB P65 between AAA and TAA specimens (P>0.05). It was concluded that OPN and NF-kappaB P65 were involved in the pathogenesis of TAA and AAA. OPN can up regulate the expression of MMP and uPA via NF-kappaB signaling pathway thereby accelerating the degradation of extracellular matrix and playing an important role in the pathogenesis and development of TAA and AAA. PMID- 22038348 TI - TMTP1, a novel tumor-homing peptide, specifically targets hematological malignancies and their metastases. AB - TMTP1, a 5-amino acid peptide NVVRQ, obtained by using the flagella peptide library screening in our previous studies, can be used for the labeling of malignant in situ and metastatic lesions, and even micro-metastases. In this study, TMTP1 was assessed for its ability to specifically target the malignant hematopoietic cells and metastatic lesions of hematological malignancies. FITC TMTP1 was chemically synthesized. Immunofluorescence assay and competitive test were carried out to determine the specific binding capacity of TMTPl to hematological malignant cell lines, including HL60, k562, SHI-1, Jurkat, Raji, El 4 and umbilical cord blood mononuclear cells. Mononuclear cells were isolated from the bone marrow of healthy subjects and patients with chronic myeloid leukemia. Then the cells were co-cultured with TMTP1 or scrambled peptides and the binding and affinity of TMTP1 peptide to the primary cells of hematological malignancies were flow cytometrically analyzed. The binding specificity of TMTP1 to target hematological malignancies was measured in vivo by intravenous injection of FITC-conjugated TMTP1 into El-4 lymphoma-bearing mice. The results showed that TMTP1 specifically bound to the cells of a series of hematological malignancies, including HL60, k562, Jurkat, Raji, El-4 and chronic myeloid leukemia primary cells but not to bone marrow mononuclear cells from healthy subjects. By contrast, TMTP1 could bind to the metastatic foci of lymphoma originating from the EL-4 cell line while the scrambled peptide failed to do so. Moreover, the occult metastases could be identified, with high specificity, by detecting FITC-TMTP1. We are led to conclude that TMTP1, as a novel tumor-homing peptide, can serve as a marker for primary malignant and metastatic lesions for the early diagnosis of hematological malignances and a carrier of anticancer drugs for cancer treatment. PMID- 22038349 TI - Comparative study on the efficacy of tiotropium bromide inhalation and oral doxofylline treatment of moderate to severe stable chronic obstructive pulmonary disease. AB - This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD). A multi-center, randomized, double blind, double-dummy, parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 MUg/day) or oral doxofylline tablets (0.2 g/time, 2 times a day) for 12 and 24 weeks. Before and after treatment for 12 weeks and 24 weeks, respectively, pulmonary function, 6-min walking distance and dyspnea index were recorded. The results showed that in both tiotropium group and doxofylline groups, after 12 week treatment, FEV(1), FEV(1)/FVC% and 6-min walk distance were significantly higher than those before the medication, while dyspnea index decreased as compared with that before treatment. After 24-week treatment, a slight improvement in the measures was observed as compared with that of 12-weeks treatment, but the difference was not statistically significant. With both 12 week and 24-week treatment, the effect of tiotropium was slightly better than that of doxofylline tablets, with the difference being statistically insignificant. The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9%) and 12 cases (12.9%), respectively, and no statistically significant difference was found between them. We are led to conclude that both tiotropium at 18 MUg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD. PMID- 22038350 TI - Effects of exogenous VEGF(165)b on invasion and migration of human lung adenocarcinoma A549 cells. AB - Vascular endothelial growth factor 165 (VEGF(165))-mediated autocrine stimulation of tumor cells enhances the progression to a malignant phenotype. VEGF(165)b competes with VEGF(165) and binds to vascular endothelial growth factor receptor (VEGFR), resulting in inhibition of downstream signal transduction pathways. This study was designed to investigate the role of VEGF(165)b in the migration and invasion of human lung adenocarcinoma A549 cells. The full-length of VEGF(165)b was constructed and cloned into an expression plasmid (pVEGF(165)b), and then transfected into A549 cells. Dimethylthiazolyl- 1 -2, 5-diphenyltetrazolium bromide (MTT) assay was used to detect the effect of VEGF(165)b on proliferation of transfected cells. Reverse transcription polymerase chain reaction (RT-PCR) was employed to examine the effect of VEGF(165)b on the expression of VEGF(165) in transfected cells. Wound-healing assays were used to investigate the effect of VEGF(165)b on migration of transfected cells. Matrix metalloproteinase (MMPs) activity assay and in vitro invasion assay were used to determine the role of VEGF(165)b in invasion of transfected cells. There was no significant change in proliferation of A549 cells after transfection of pVEGF(165)b, but the expression of VEGF(165), migration and invasion in A549 cells were inhibited. Furthermore, exogenous VEGF(165)b inhibited the activity of MMP9 in the supernatant of A549 cells and the subsequent invasion capacity of those cells. We therefore conclude that exogenous VEGF(165)b can inhibit the expression of VEGF(165), as well as the migration and invasion of A549 cells, but has no effect on the proliferation of A549 cells. PMID- 22038351 TI - Interleukin-10 is expressed in HepG2.2.15 cells and regulated by STAT1 pathway. AB - This study investigated the expression profiles of IL-10 gene in three human hepatoma cell lines including Huh7, HepG2, and HepG2 transfected with a plasmid containing hepatitis B virus (HBV) named HepG2.2.15. RT-PCR analysis demonstrated that IL-10 message RNA was absent in HepG2 and Huh7 cells, whereas it was present in HepG2.2.15 cells, which was consistent with ELISA result. Furthermore, except for lamivudine other antiviral treatments did not significantly decrease the HBV DNA level in HepG2.2.15 cells, while they had different effects on the expression of IL-10 protein, although stimulation by LPS had no significant effect. In addition, except for poly(I:C), the other treatments decreased the expression of IL-10 protein to different degrees, but had no significant effects on the expression of NF-kappaB and MyD88. Meanwhile, all treatments we used had effect on the expression of STAT1. In conclusion, IL-10 was expressed in HepG2.2.15 cells and STAT1 pathway might be involved in the regulation of IL-10 expression in HepG2.2.15 cells, but it was not the sole pathway, the exact mechanism warrants further study. PMID- 22038352 TI - Effects of hydrogen sulfide on a rat model of sepsis-associated encephalopathy. AB - To investigate the interaction and involvement of sodium hydrosulfide (NaHS), a H(2)S donor, on hippocampus of rats suffering from sepsis-associated encephalopathy, rats were subjected to cecal ligation and puncture (CLP)-induced sepsis. Adult male Sprague-Dawley rats were randomly divided into four groups: Sham group, CLP group, CLP+NaHS group and CLP+aminooxyacetic acid (AOAA, an inhibitor of H(2)S formation) group. The four groups were observed at 3, 6, 9, 12 h after treatment. We examined hippocampal H(2)S synthesis and the expression of cystathionine-beta-synthetase (CBS), a major enzyme involved in the H(2)S synthesis in hippocampus. CBS expression was detected by reverse transcription polymerase chain reaction (RT-PCR). The concentrations of inflammatory cytokines (TNF-alpha, IL-1beta) were determined in hippocampus by using enzyme-linked immunosorbent assay (ELISA). Neuronal damage was studied by histological examination of hippocampus. In CLP group, H(2)S synthesis was significantly increased in hippocampus compared with sham group and it peaked 3 h after CLP (P<0.05). Sepsis also resulted in a significantly upregulated CBS mRNA in hippocampus. The levels of TNF-alpha and IL-1beta in the hippocampus were substantially elevated at each time point of measurement (P<0.05), and they also reached a peak value at about 3 h. Administration of NaHS significantly aggravated sepsis-associated hippocampus inflammation, as evidenced by TNF-alpha and IL-1beta activity and histological changes in hippocampus. In septic rats pretreated with AOAA, sepsis-associated hippocampus inflammation was reduced. It is concluded that the rats subjected to sepsis may suffer from brain injury and elevated pro-inflammatory cytokines are responsible for the process. Furthermore, administration of H(2)S can increase injurious effects and treatment with AOAA can protect the brain from injury. PMID- 22038353 TI - Are surgical indications of Barcelona Clinic Liver Cancer staging classification justified? AB - Liver resection is the most effective treatment for hepatocellular carcinoma (HCC). The Barcelona Clinic Liver Cancer (BCLC) staging system is commonly accepted as a guideline for HCC treatment, but it only recommends liver resection for the patients with HCC at stage 0 to A1. The surgical indications of the BCLC staging system need to be re-evaluated. 120 HCC patients undergoing curative liver resection were retrospectively stratified to the BCLC staging system, and the survival of the patients at stages A, B and C was analyzed. The justification of the BCLC staging system was re-evaluated. Fifty-two patients were classified at stage A, 51 at stage B and 17 at stage C respectively. The hospital mortality of this cohort was zero and the morbidity was 24.1%. The 1-, 2-, 3-year overall survival rate of this cohort was 81.6%, 68.3%, and 57.5% respectively. There was no significant difference in the survival rate between the patients at stage A and B (P>0.05). If the treatment guidelines of BCLC staging system were followed, the majority of the patients at stages A and B (77.7%, 80/103) would not have been treated surgically. Our data suggest that the surgical indications of the BCLC staging system are not justified for HCC treatment. More studies may be needed as for how to further broaden the surgical indications of the BCLC staging system in the future. PMID- 22038354 TI - Up-regulation of Tim-3 expression contributes to development of burn-induced T cell immune suppression in mice. AB - T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3(+) T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4(+) and CD8(+) T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-gamma and TNF-alpha, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3(+) T cells subsets were more prone to spontaneous apoptosis than Tim-3(-) T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression. PMID- 22038355 TI - Neuroprotection of erythropoietin and methylprednisolone against spinal cord ischemia-reperfusion injury. AB - Recent research based on various animal models has shown the neuroprotective effects of erythropoietin (EPO). However, few studies have examined such effects of EPO in the clinic. In this study we enrolled patients with spinal cord ischemia-reperfusion (I-R) injury to investigate the clinical application of EPO and methylprednisolone (MP) for the neuroprotection against spinal cord I-R injury. Retrospective analysis of 63 cases of spinal cord I-R injury was performed. The Frankel neurological performance scale was used to evaluate the neurological function after spinal cord injury (SCI), including 12 cases of scale B, 30 cases of scale C, and 21 cases of scale D. These cases were divided into 2 groups: group A (27 cases) got treatment with both EPO and MP; group B (36 cases) got treatment with MP only. The neurological function of patients after treatment was evaluated by American Spinal Cord Injury Association (ASIA) index score, and activity of daily living (ADL) of the patients was also recorded. All patients got follow-up and the follow-up period ranged from 24 to 39 months (mean 26 months). There was no significance difference in neurological function between groups A and B before the treatment (P>0.05). However, the neurological function and ADL scores were significantly improved 1 week, 1 year or 2 years after the treatment compared to those before the treatment (P<0.05), and the improvement was more significant in group A than in group B (P<0.05). It is suggested that the clinical application of EPO and MP provides the neuroprotection against spinal cord I-R injury. PMID- 22038357 TI - Components in melanoma cytoplasm might induce murine BMSCs transformation and expression of Melan-A. AB - This study explored the possibility that the components in melanoma cytoplasm induce murine BMSCs transformation and expression of Melan-A by morphologically observing the changes of BMSCs and immunocytochemically detecting Melan-A in the cells after culturing BMSCs in medium containing melanoma cytoplasm components (MCC). MCC of B16 melanoma cells was prepared and BMSCs were cultured and induced by adding the MCC into culture medium. The cells were morphologically observed and Melan-A was immunohistochemically detected to confirm BMSCs transformation. MCC-induced BMSCs underwent morphological changes. A number of melanin granules appeared in the cytoplasm of the cells and some were released into surrounding areas. Several cells that might come from one cell formed a cluster, and their granules, together with those secreted by other induced BMSCs, formed a so-called "sphere-formed structure". The induced BMSCs expressed Melan-A. We are led to conclude that there might be some factors in the cytoplasm of melanoma cells that might induce BMSCs transformation toward melanogenic cell, or even melanoma. PMID- 22038356 TI - Specific inhibitory protein Dkk-1 blocking Wnt/beta-catenin signaling pathway improve protectives effect on the extracellular matrix. AB - The present study examined the role of Wnt/beta-catenin signaling pathway in the degeneration of nucleus pulposus cells and the protective effect of DKK1 on nucleus pulposus cells. The model of nucleus pulposus cell degeneration was induced by intra-disc injection of TNF-alpha, and the expression of beta-catenin protein was detected by Western blotting. The cultured rabbit nucleus pulposus cells were divided into 4 groups. In group A, the cells were cultured with normal medium and served as control group. In group B, the cells were cultured with TNF alpha and acted as degeneration group. In group C, the cells were cultured with TNF-alpha and transfected with Adv-eGFP and was used as fluorescence control group. In group D, the cells were cultured with TNF-alpha and transfected with Adv-hDKK1-eGFP, serving as intervention group. The expression of type II collagen, proteoglycan, beta-catenin, and MMP-13 in each group was detected by immunocytochemistry and RT-PCR. The result showed that TNF-alpha increased the expression of beta-catenin and MMP-13, and significantly inhibited the synthesis of type II collagen and proteoglycan, which resulted in the degeneration of nucleus pulposus cells. This effect could be obviously reversed by DKK1. We are led to concluded that TNF-alpha could activate the Wnt/beta-catenin signaling pathway, and increase the expression of MMP-13, thereby resulting in disc degeneration. Specifically blocking Wnt/beta-catenin signaling pathway by DKK-1 could protect the normal metabolism of intervertebral disc tissue. The Wnt pathway plays an important role in the progression of the intervertebral disc degeneration. PMID- 22038358 TI - Effect of over-expressed LRIG3 on cell cycle and survival of glioma cells. AB - This study examined the effects of over-expression of leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3) on the cell cycle and survival of human glioma cell line U87 and U251 and explored the possible mechanisms. The LRIG3 gene was transduced into U87 and U251 cells respectively by using lentivirus and the transduced cells were selected by puromycin. The changes in LRIG3 mRNA and protein levels were measured by RT-PCR and Western blotting. The apoptosis rate was detected by Annexin V-FITC/PI double labeling and the cell cycle was flow cytometrically analyzed. Compared with control cells, LRIG3 mRNA expression in U251 and U87 cells transduced with pLVX-DsRed-LRIG3-Monomer-N1 were increased by 77.6% and 129.7%, and LRIG3 protein expression was raised by 141.3% and 322.7%, respectively. Cell cycle analysis showed that LRIG3 over-expression increased the percentage of cells at G(0)/G(1) phase (P<0.01). Over-expressed LRIG3 could significantly promote the apoptosis of U87 and U251 cells (P<0.05). These findings suggest that the over-expression of LRIG3 could arrest the cell cycle in G(0)/G(1) phase, and promote apoptosis of U87 and U251 cells. PMID- 22038359 TI - Antilithic effects of extracts from Urtica dentata hand on calcium oxalate urinary stones in rats. AB - This study examined the potential antilithic effects of a traditional Chinese medicine Urtica dentata Hand (UDH) in experimental rats and screened the optimal extract of UDH as a possible therapeutic agent for kidney stones. The rat model of urinary calcium oxalate stones was induced by intragastric (i.g.) administration of 2 mL of 1.25% ethylene glycol (EG) and 1% ammonium chloride (AC) for 28 days and was confirmed by Color Doppler ultrasound imaging. The rats in different experimental groups were then intragastrically given petroleum ether extract (PEE), N-butanol extract (NBE), aqueous extract (AqE) of UDH, Jieshitong (positive control drug), and saline, respectively. Treatment with NBE significantly reduced the elevated levels of urinary calcium, uric acid, phosphate, as well as increased urinary output. Accordingly, the increased calcium, oxalate levels and the number of calcium oxalate crystals deposits were remarkably reverted in the renal tissue of NBE-treated rats. In addition, NBE also prevented the impairment of renal function to decrease the contents of blood urea nitrogen (BUN) and creatinine. Taken together, these data suggest that NBE of UDH has a beneficial effect on calcium oxalate urinary stones in rats by flushing the stones out and protecting renal function. PMID- 22038360 TI - Design and efficacy of surgery for horizontal idiopathic nystagmus with abnormal head posture and strabismus. AB - The design and efficacy of surgery for horizontal idiopathic nystagmus (HIN) with abnormal head posture and strabismus were investigated. Different surgical procedures were selected according to the angle of head turn in 44 cases of HIN with abnormal head posture and strabismus. For patients with a head turn of 15 degrees or less, the Anderson procedure was used; the yoke muscles were recessed upon slow-phase. For patients with a head turn between 15 degrees and 25 degrees , the surgery was designed as a Kestenbaum 5-4-4-5 procedure. For patients with a head turn of 25 degrees or more, the surgery was designed as a Parks 5-8-6-7 procedure. The surgery to correct the abnormal head posture was performed on the fixating eye while that to correct the deviation was then performed on the non fixating eye at the same time. The amount of surgery of the horizontal rectus muscles on the non-fixating eye was sum of the angle of head turn and the degree of deviation, which was calculated as follows: recession/resection amount of medial and lateral rectis / 2*5 =angle of head turn +/- degree of deviation. The results showed as follows: (1) Visual acuity: the visual acuity in the primary ocular position increased two lines or more in 35 patients, accounting for 79.55%. Nine patients had no or only one-line improvement, accounting for 20.45% of the entire study population; (2) The degree of deviation in the primary ocular position: 37 cases had a normal primary ocular position or the degree of deviation <= 8(delta) after surgery, accounting for 84.09%. Six patients had a residual degree of deviation of 8(delta)-15(delta), accounting for 13.64%. One patient had a residual degree of deviation >20(delta), accounting for 2.27% of the patients examined; (3) Abnormal head posture: 34 patients had a normal head posture or a head turn of less than 5 degrees , accounting for 72.27%. Eight patients had a residual head turn of 5 degrees -15 degrees , accounting for 18.18%. Two patients had a head turn of 15 degrees -25 degrees , accounting for 4.55%. It was concluded that different surgical procedures based on the angle of head turn and the relationship between deviation and null zone can eliminate anomalous head posture, correct deviation, and improve vision acuity in the primary ocular position. PMID- 22038361 TI - Muscarinic acetylcholine receptor subtype expression in type vestibular hair cells of guinea pigs. AB - Recent studies have demonstrated that five subtypes (M1-M5) of muscarinic acetylcholine receptor (mAChR) are expressed in the vestibular periphery. However, the exact cellular location of the mAChRs is not clear. In this study, we investigated whether there is the expression of M1-M5 muscarinic receptor mRNA in isolated type II vestibular hair cells of guinea pig by using single-cell RT PCR. In vestibular end-organ, cDNA of the expected size was obtained by RT-PCR. Moreover, mRNA was identified by RT-PCR from individually isolated type II vestibular hair cells (single-cell RT-PCR). Sequence analysis confirmed that the products were M1-M5 mAChR. These results demonstrated that M1-M5 mAChR was expressed in the type II vestibular hair cells of the guinea pig, which lends further support for the role of M1-M5 mAChR as a mediator of efferent cholinergic signalling pathway in vestibular hair cells. PMID- 22038363 TI - A novel technique for the preparation of (125)I-5-trimethylstannyl-1-(2-deoxy-2 fluoro-beta-D-arabino-furanosyl) uracil [correction of urail] and its biodistribution pattern in Kunming mice. AB - In this study, a novel technique for the preparation of (125)I-5-trimethylstannyl 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) urail (FIAU) was developed, (125)I FIAU biodistribution profile was detected in Kunming mice and the possibility of using FTAU radio-labeling for reporter gene imaging was explored. 5 trimethylstannyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) urail (FTAU) was labeled with radioiodine ((125)I). A rotary evaporation method was used to remove excess methanol. The reactant was purified through a Sep-Pak C18 reversal phase column. The radiochemical purity and in vivo stability were determined using silica gel thin layer chromatography (TLC). The biodistribution of (125)I-FIAU in Kunming mice was also detected. The results showed that (125)I-FIAU could be radiolabeled effectively with FTAU, with mean labeling rate being (81+/-0.38)% (n =5). The mean radiochemical purity of (98.01+/-0.40)% (n=5) was achieved after a reversal phase Sep-park column purification. (125)I-FIAU was stable when incubated in normal human serum or in saline at 37 degrees C, with a radiochemical purity >96% during a 0.5-24 h time period. Biological experiments exhibited rapid clearance of (125)I-FIAU from the blood pool. (125)I-FIAU was mostly excreted by kidneys. (125)I-FIAU in myocardium dropped conspicuously after 8 h and there was hardly retention at 24 h. We were led to concluded that the new method of radioiodinization of FTAU for the preparation of (125)I-FIAU is easy, highly effective and stable in vivo. The biodistribution of (125)I-FIAU in Kunming mice showed it can serve as an imaging probe for myocardial reporter genes. PMID- 22038362 TI - Non-invasive prenatal diagnosis of trisomy 21 by dosage ratio of fetal chromosome specific epigenetic markers in maternal plasma. AB - This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Maternal plasma samples were collected from 388 singleton pregnancies, and placental or chorionic villus tissues from 112 of them. Methylation-specific PCR (MSP) and methylation-sensitive restriction enzyme digestion followed by fluorescent quantitative PCR (MSRE + PCR) were employed to detect the maternal-fetal methylation difference in AIRE and RASSF1A. Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues. Moreover, the differential methylation for each locus could be seen during the whole pregnant period. The positive rates of fetal AIRE and RASSF1A in maternal plasma were found to be 78.1% and 82.1% by MSP and 94.8% and 96.9% by MSRE + PCR. MSRE + PCR was superior to MSP in the identification of fetal-specific hypermethylated sequences (P<0.05). Based on the data from 266 euploidy pregnancies, the 95% reference interval of the fetal AIRE/RASSF1A ratio in maternal plasma was 0.33-1.77, which was taken as the reference value for determining the numbers of fetal chromosome 21 in 102 pregnancies. The accuracy rate in 98 euploidy pregnancies was 96.9% (95/98). Three of the four trisomy 21 pregnancies were confirmed with this method. It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21. PMID- 22038364 TI - An open CAM system for dentistry on the basis of China-made 5-axis simultaneous contouring CNC machine tool and industrial CAM software. AB - China-made 5-axis simultaneous contouring CNC machine tool and domestically developed industrial computer-aided manufacture (CAM) technology were used for full crown fabrication and measurement of crown accuracy, with an attempt to establish an open CAM system for dental processing and to promote the introduction of domestic dental computer-aided design (CAD)/CAM system. Commercially available scanning equipment was used to make a basic digital tooth model after preparation of crown, and CAD software that comes with the scanning device was employed to design the crown by using domestic industrial CAM software to process the crown data in order to generate a solid model for machining purpose, and then China-made 5-axis simultaneous contouring CNC machine tool was used to complete machining of the whole crown and the internal accuracy of the crown internal was measured by using 3D-MicroCT. The results showed that China made 5-axis simultaneous contouring CNC machine tool in combination with domestic industrial CAM technology can be used for crown making and the crown was well positioned in die. The internal accuracy was successfully measured by using 3D MicroCT. It is concluded that an open CAM system for dentistry on the basis of China-made 5-axis simultaneous contouring CNC machine tool and domestic industrial CAM software has been established, and development of the system will promote the introduction of domestically-produced dental CAD/CAM system. PMID- 22038365 TI - Correlation study on expression of GST-pi protein in brain tissue and peripheral blood of epilepsy rats induced by pilocarpine. AB - Previous studies have suggested that glutathione-S-transferase pi (GST-pi) over expression in the brain tissue is associated with refractory epilepsy. However, whether the change in GST-pi level in the peripheral blood is in line with that in brain tissue remains unknown. This study examined the correlation between GST pi in brain tissue and that in peripheral blood in rat models of pilocarpine induced refractory epilepsy. The animals were divided into drug-resistant group and drug-responsive group according to the response to anti-epileptic drugs. GST pi expression in brain tissue was immunohistochemically determined, while the expression of GST-pi in peripheral blood was analyzed by Western blotting. In the hippocampus and cortex, GST-pi was mainly found in the cytoplasm and membrane of neurons, and the GST-pi expression level was higher in drug-resistant group than in the drug-responsive group and saline control group (P<0.05). Moreover, there was no significant difference between responders and saline control animals (P>0.05). The change in expression of GST-pi in peripheral blood showed the same pattern as that in brain tissues, suggesting GST-pi might contribute to drug resistance in epilepsy. Importantly, the GST-pi over-expression in peripheral blood could be used as a marker for resistance to anti-epileptic agents. PMID- 22038366 TI - A meta-analysis of the biomarkers associated with coronary artery lesions secondary to Kawasaki disease in Chinese children. AB - The biomarkers associated with coronary artery lesions (CAL) secondary to Kawasaki disease (KD) in Chinese children were investigated by using Meta analysis. We searched documents published from January 1997 to December 2009 from medical electronic databases. According to inclusion and exclusion criteria, eligible full-text papers were identified. We conducted a comprehensive quantitative analysis by using Stata10.0 statistical software package to assess the heterogeneity among the documents, calculated the summary effect and analyze publication bias and sensitivity. A total of 92 documents and 16 biomarkers were identified. All documents were case-control studies, and included 2398 patients in CAL group and 5932 patients in non-CAL (NCAL) group. The Meta-analysis showed that the levels of platelet count, platelet hematocrit (PCT), neutrophils count, platelet distribution width (PDW), mean platelet volume (MPV), erythrocyte sedimentation rate (ESR), cardiac troponin I (cTnI), and endothelin-1 (ET-1) in CAL group were significantly higher than those in NCAL group, and serum albumin (Alb) and hemoglobin (Hb) levels were significantly lower in CAL group (all P<0.05). White blood cell (WBC) count, serum sodium, matrix metalloproteinase 9 (MMP-9), total cholesterol (TC), hematocrit (HCT) and CD3+T lymphocytes percentage had no statistically significant difference between the two groups. In conclusion, our results indicated that the 10 biomarkers including platelet count, neutrophils count, PCT, PDW, MPV, ESR, cTnI, ET-1, Alb and Hb were associated with CAL, and may be involved in the pathogenesis of CAL. The biomarkers of WBC count, serum sodium, MMP-9, TC, HCT, and CD3+T lymphocytes percentage bore no relationship with the development of CAL among Chinese children with KD. PMID- 22038367 TI - Correlation analysis on total lymphocyte count and CD4 count in HIV-infected patients: a retrospective evaluation. AB - CD4 count is the standard method for determining eligibility for highly active antiretroviral therapy (HAART) and monitoring HIV/AIDS disease progression, but it is not widely available in resource-limited settings. This study examined the correlation between total lymphocyte count (TLC) and CD4 count of HIV-infected patients before and after HAART, and assessed the thresholds of TLC for making decisions about the initiation and for monitoring HAART. A retrospective study was performed, and 665 HIV-infected patients with TLC and CD4 count from four counties (Shangcai, Queshan, Shenqiu and Weishi) were included in the study. Pearson correlation and receiver operating characteristic (ROC) were used. TLC and CD4 count after HAART was significantly increased as compared with pre-HAART (P<0.01). An overall positive correlation was noted between TLC and CD4 count (pre-HAART, r=0.73, P=0.0001; follow-up HAART, r=0.56, P=0.0001). The ROC curve between TLC and CD4 count showed that TLC <= 1200 cells/mm(3) could predict CD4 < 200 cells/mm(3) with a sensitivity of 71.12%, specificity of 66.35% at pre-HAART. After 12-month HAART, the optimum prediction for CD4 count < 200 cells/mm3 was a TLC <= 1300 cells/mm(3), with a sensitivity of 63.27%, and a specificity of 74.84%. Further finding indicated that TLC change was positively correlated to CD4 change (r=0.77, P=0.0001) at the time point of 12-month treatment, and the best prediction point of TLC change for CD4 increasing was 135 cells/mm(3). TLC and its change can be used as a surrogate marker for CD4 count and its change of HIV-infected individuals for making decisions about the initiation and for monitoring HAART in resource-limited settings. PMID- 22038368 TI - Clinical and histopathological review of 229 cases of ranula. AB - The purpose of this paper was to evaluate the relationship between the thrombosis and secretory duct dilation, lesion size, clinical types, nature (primary or recurrent) and duration of illness in the development of ranula. A total of 229 cases of sublingual gland cysts were treated with surgical resection from Jan. 1990 to Feb. 2010. The patients' data were investigated on histopathological findings, size of ranula, the clinical types, nature of ranula (primary or recurrent) and duration of illness. Sections from the paraffin-embedded blocks were HE-stained. CK expression was immunohistochemically detected. Among 229 cases the incidence of venous thrombosis was 58.52%. The incidence of venous thrombosis with or without duct dilation was 73.25% and 26.39% respectively, with a significant difference between the two groups (P<0.005). The incidence of venous thrombosis of ranulas with diameter larger or less than 3 cm was 72.22% and 46.28% (P<0.005). The incidence of venous thrombosis of oral ranula, plunging ranula and mixed ranula was 49.37%, 77.19% and 85.71% respectively, with a significant difference found between oral and plunging or mixed ranula (P<0.01). The incidence of venous thrombosis in ranula patients with duration of illness longer or less than 3 months was 69.77% and 51.75% (P<0.01). The incidence of venous thrombosis with recurrent and primary ranulas was 51.85% and 64.85%, without a significant difference noted between them (P>0.05). It is concluded that the formation of venous thrombosis was related to the dilation of secretory duct, lesion size, clinical types, duration of lesion but formation of venous thrombosis was not related to the nature (primary or recurrent) of ranulas. PMID- 22038369 TI - Intense association of non-culturable endophytic bacteria with antibiotic cleansed in vitro watermelon and their activation in degenerating cultures. AB - The study was undertaken with a view to unravel the source of bacterial colony growth observed in a section of micropropagated triploid watermelon cultures that were supposedly cleansed of the associated endophytic bacteria through antibiotic treatment, and thereafter maintained under stringent sterility checks to prevent lateral intrusion of contaminants. Five different bacteria were retrieved from colony growth-displaying watermelon cultures that were previously treated with gentamycin and five isolates from cefazolin-treated stocks with the organisms showing tolerance to the respective antibiotic. These watermelon cultures were in degeneration phase (over 6 months after the previous sub-culturing), while the actively maintained counterpart stocks appeared healthy with no colony growth on different bacteriological media during tissue-screenings. The latter cultures, however, revealed abundant motile, tetrazolium-stained bacterial cells in microscopy, suggesting tissue colonization by non-culturable endophytes. PCR screening on healthy cultures endorsed tissue colonization by different bacterial phylogenic groups. A few organisms could be activated to cultivation from healthy watermelon stocks through host tissue extract supplementation, which also enhanced the growth of all the organisms. The study indicated that a fraction of antibiotic-tolerant bacteria survived intra-tissue in non-culturable form during the preceding cleansing activity, multiplied to substantial numbers thereafter, and turned cultivable in degenerating cultures contributed by tissue breakdown products. This study brings out the existence of a deep endophyte association in tissue cultures which is not easily dissociable. It also signifies the utility of in vitro system for investigations into plant-endophyte association and to bring normally non-culturable novel organisms to cultivation facilitating their future exploitation. PMID- 22038370 TI - An ethylene response factor (ERF5) promoting adaptation to drought and salt tolerance in tomato. AB - A novel member of the AP2/ERF transcription factor family, SlERF5, was identified from a tomato mature leaf cDNA library screen. The complete DNA sequence of SlERF5 encodes a putative 244-amino acid DNA-binding protein which most likely acts as a transcriptional regulator and is a member of the ethylene responsive factor (ERF) superfamily. Analysis of the deduced SlERF5 protein sequence showed that it contained an ERF domain and belonged to the class III group of ERFs proteins. Expression of SlERF5 was induced by abiotic stress, such as high salinity, drought, flooding, wounding and cold temperatures. Over-expression of SlERF5 in transgenic tomato plants resulted in high tolerance to drought and salt stress and increased levels of relative water content compared with wild-type plants. This study indicates that SlERF5 is mainly involved in the responses to abiotic stress in tomato. PMID- 22038371 TI - Metabolite profiling of the moss Physcomitrella patens reveals evolutionary conservation of osmoprotective substances. AB - The moss Physcomitrella patens is suitable for systems biology studies, as it can be grown axenically under standardised conditions in plain mineral medium and comprises only few cell types. We report on metabolite profiling of two major P. patens tissues, filamentous protonema and leafy gametophores, from different culture conditions. A total of 96 compounds were detected, 21 of them as yet unknown in public databases. Protonema and gametophores had distinct metabolic profiles, especially with regard to saccharides, sugar derivates, amino acids, lignin precursors and nitrogen-rich storage compounds. A hydroponic culture was established for P. patens, and was used to apply drought stress under physiological conditions. This treatment led to accumulation of osmoprotectants, such as altrose, maltitol, ascorbic acid and proline. Thus, these osmoprotectants are not unique to seed plants but have evolved at an early phase of the colonization of land by plants. PMID- 22038372 TI - Genistein downregulates presenilin 1 and ubiquilin 1 expression. AB - The aim of this study was to determine the effects of several food ingredients and chemical inhibitors on the expression of presenilin, a molecule involved in gamma-secretase activity and the generation of amyloid-beta peptide in Alzheimer's disease. Western blotting revealed the downregulation of presenilin 1 protein expression by stimulation with genistein in vitro, while the effects on presenilin 1 gene expression examined by reverse transcriptase-polymerase chain reaction (RT-PCR) were unaltered in Daudi cells. Genistein likely downregulates presenilin via the inhibition of ubiquilin 1 expression in lymphoid cells. Our findings provide new insights that may help to establish preventive strategies against Alzheimer's disease. PMID- 22038373 TI - The impact of self-stigma and mutual help programs on the quality of life of people with serious mental illnesses. AB - Mutual help programs (MHPs) are informal services developed and operated by people with serious mental illnesses for peers with these illnesses. We expect MHPs to have positive effects on quality of life and inverse associations with self-stigma. We hypothesize group identification and social support to be key ingredients that lead to MHPs benefits and hence to also be significant correlates. Eighty-five people with serious mental illness reported current and past MHP experience and completed self-report measures of quality of life, self stigma, group identification, and social support. Self-stigma was shown to be a significant and large correlate of quality of life. Satisfaction with current and past MHP participation was also associated with quality of life. Group identification and satisfaction with one's support network were significantly and largely associated with MHP satisfaction. MHPs are a specific example of the broader category of consumer operated services which also include drop-in centers and education-for-advocacy programs. Findings about group identification will inform ongoing development of MHPs and consumer operated services, as well as evaluation of these programs. PMID- 22038374 TI - Lay diagnoses and views on causes, coping strategies, and treatment for schizophrenia. AB - We aimed to clarify the relationship between lay diagnoses and perspectives on schizophrenia regarding causes, coping strategies, treatments, prognosis with and without the help of specialists. Our study sample was 500 adults in Japan. Participants read a vignette that depicted moderate to severe schizophrenic symptoms and yielded lay diagnoses. They also expressed their perspectives on the cause of the status in the vignette and coping strategies. We examined the relationship between lay diagnoses and the perspectives. Participants labeled the vignette as 'stress' held low expectations for the effectiveness of mental health professionals and psychiatric treatment. To enhance mental health literacy, it is important to help people distinguish a mental illness from mere stress. Lay diagnoses do not necessary have to be detailed, as long as people recognize a situation as an illness. PMID- 22038375 TI - Case-control study of the relationship of functioning to suicide in a community based sample of individuals with schizophrenia in China. AB - Suicide is a leading cause of premature death among people with schizophrenia. Some studies indicate that increased difficulties in functioning are associated with suicidality in persons with schizophrenia. We conducted a secondary analysis of 74 suicides (cases) and 24 accidental deaths (controls) among persons with schizophrenia identified in a national psychological autopsy study in China. Between cases and controls, we compared the effect of schizophrenia on work, daily activities, emotions, social relationships and self-care at the time the illness was most severe. There was no difference in the overall maximum dysfunction associated with the illness between groups. None of the 5 measures (work, activities, emotions, relationships, self-care) were different between the two groups. This study of individuals with DSM-IV schizophrenia who died by suicide in a non-western culture only partially supports findings from clinical studies in western cultures. PMID- 22038376 TI - Uptake of Web-based clinical resources from the MacArthur Initiative on Depression and Primary Care. AB - This study assessed the usability and desired enhancements for the MacArthur Foundation's Depression and Primary Care (MDPC) Web site to determine if resources for integrated depression care that are disseminated through the Web site are incorporated into routine clinical care. Since its launch in 2003, more than 20,000 users registered as members of the MDPC website to read and download depression care resources. Subjects were randomly selected from MDPC Web site users who had previously downloaded the depression toolkit. Web-based survey, which was administered anonymously, included the following domains: (1) socio demographic data, (2) confidence in managing depression (3) Web site content and design features, (4) desired enhancements to Web site and content, (5) use of resources downloaded from the Web site, and (6) importance of depression care resources. Of the 3,478 randomly selected participants, 666 (19.1%) responded. Web site content was rated "good" or "excellent" for screening and diagnosis (84.3%), treatment (69.8%), patient education (66.2%), and care management (66.9%). The Patient Health Questionnaire-9 (PHQ-9) was rated "very useful" by 68.3%; 47.1% reported using it in at least 25% of encounters with patients who are depressed. PHQ-9 use was significantly associated with higher self-confidence in managing depression (P = 0.05). Evidence-based resources for depression care can be disseminated effectively through a dedicated Web site and may help clinicians incorporate effective care models into routine practice. PMID- 22038377 TI - Doping awareness, views, and experience: a comparison between general practitioners and pharmacists. AB - PURPOSE: Information about doping awareness among medical professionals is scarce. We evaluated the attitudes, level of knowledge and experience among general practitioners (GPs) and pharmacists (Ps) with regard to doping. METHODS: In a cross-sectional national survey a 59-item self-administered questionnaire was sent to a representative random sample of 645 GPs and 330 Ps. RESULTS: Overall, 204/975 (133 GPs, 71 Ps) questionnaires were returned and available for analysis. Fewer than half (39% GPs vs. 48% Ps, P = 0.702) of respondents were familiar with the formal definition of doping. The abbreviation WADA was correctly interpreted by 42% (33% vs. 59%, P = 0.003), and 65% knew that the European Commission has the legislation to fight against doping. More GPs (69% vs. 31%, P = 0.005) agreed to have a role to play in doping prevention, similar proportions considering themselves to have sufficient knowledge of prevention initiatives (65% vs. 35%, P = 0.369). Overall, 12% of respondents (8.7% GPs, 19.3% Ps) reported being directly confronted with a request for prescription of doping agents in the previous 12 months (mainly stimulants, anabolic agents, hormones, corticosteroids). CONCLUSIONS: GPs and Ps are frequently exposed to questions about and requests for doping agents. They have acceptable level of general knowledge but are in need for more specific information on prohibited substances and legislature. PMID- 22038378 TI - [Consensus diagnosis and therapy of soft tissue sarcoma]. AB - Soft tissue sarcomas are heterogeneous tumours and relatively uncommon. There have been advances over the past years concerning pathology, clinical behaviour, diagnosis strategies and the treatment. To summarize these advances as well as making it public is one of the goals of the following consensus guidelines. But why do we need special guidelines for Austria? There are international guidelines published by the European Society of Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN). The cause is that we need an explanation of the matrix the ESMO and the NCCN gave according to our clinical practice, the local requirements and facilities in Austria. The following recommendations were drawn up following a consensus meeting of sarcoma specialists from the three high volume centres located at the medical universities in Austria. All fields of involved physicians from diagnosis to therapy worked together to know that soft tissue sarcomas are an interdisciplinary challenge and multimodal treatment is essential. For this reason, these guidelines not only explain but also give the state of the art and clear recommendations. One of the most important guidelines is that any patient with a suspected soft tissue sarcoma should be referred to one of the three university centres and managed by a specialist sarcoma multidisciplinary team. We hope that the consensus is helpful for the clinical practice and improves the quality of care for patients with soft tissue sarcomas in Austria. PMID- 22038379 TI - Biliary cystadenoma: short- and long-term outcome after radical hepatic resection. AB - The intrahepatic biliary cystadenoma is a rare benign tumor of the liver, originating from an intrahepatic bile duct: it becomes symptomatic only when it causes obstruction of the bile duct itself. Regardless of the various diagnostic modalities available, it is difficult to distinguish preoperatively the cystadenoma both from a simple liver cyst, and from a cystic carcinoma of the bile duct. An incomplete surgical removal of the cyst often results in a higher risk of size increase and recurrence, even considering that the lesion may degenerate into a cystadenocarcinoma. Between January 2004 and May 2011, 1,173 liver resections were carried out at the Hepatobiliary Surgery Unit of San Raffaele Hospital: 12 of these were performed for cystadenoma. Forty-six patients underwent laparoscopic liver cysts deroofing: definitive histological examination in six of these patients revealed instead the diagnosis of cystadenoma. In 50% of cases, the diagnosis of cystadenoma was therefore acquired as a result of an incidental finding. The patients were all female, median age 45 years. The liver resection included six cases of left hepatectomy, three left lobectomies, and three of the right hepatectomy. The operations were performed by laparotomy, with the exception of two left lobectomies completed laparoscopically. In all cases, the postoperative course was without major complications. The resection was radical in all cases and the median hospital stay was 5 days. At a median follow up of 16 months (range 7-30), all patients are alive and disease free. Biliary cystadenomas can easily be misunderstood and interpreted as simple hepatic cysts. Radical surgical resection is necessary and provides good short- and long-term outcomes. PMID- 22038380 TI - Presence of supercooling-facilitating (anti-ice nucleation) hydrolyzable tannins in deep supercooling xylem parenchyma cells in Cercidiphyllum japonicum. AB - Xylem parenchyma cells (XPCs) in trees adapt to subzero temperatures by deep supercooling. Our previous study indicated the possibility of the presence of diverse kinds of supercooling-facilitating (SCF; anti-ice nucleation) substances in XPCs of katsura tree (Cercidiphyllum japonicum), all of which might have an important role in deep supercooling of XPCs. In the previous study, a few kinds of SCF flavonol glycosides were identified. Thus, in the present study, we tried to identify other kinds of SCF substances in XPCs of katsura tree. SCF substances were purified from xylem extracts by silica gel column chromatography and Sephadex LH-20 column chromatography. Then, four SCF substances isolated were identified by UV, mass and nuclear magnetic resonance analyses. The results showed that the four kinds of hydrolyzable gallotannins, 2,2',5-tri-O-galloyl alpha,beta-D-hamamelose (trigalloyl Ham or kurigalin), 1,2,6-tri-O-galloyl-beta-D glucopyranoside (trigalloyl Glc), 1,2,3,6-tetra-O-galloyl-beta-D-glucopyranoside (tetragalloyl Glc) and 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside (pentagalloyl Glc), in XPCs exhibited supercooling capabilities in the range of 1.5-4.5 degrees C, at a concentration of 1 mg mL-1. These SCF substances, including flavonol glycosides and hydrolyzable gallotannins, may contribute to the supercooling in XPCs of katsura tree. PMID- 22038381 TI - Comparison of chromosomal abnormality rates in ICSI for non-male factor and spontaneous conception. AB - OBJECTIVE: To compare cytogenetic data of first-trimester missed abortions in intracytoplasmic sperm injection (ICSI) for non-male factor-mediated and spontaneous pregnancies. METHODS: Using karyotype analysis, we conducted a retrospective cohort trial of missed abortions following ICSI for non-male factor and spontaneous pregnancies. Patients experienced missed abortions during the first 12 weeks of pregnancy. Dilation and curettage procedure was performed followed by cytogenetic evaluations. Two patient groups were created: ICSI (n = 71) and spontaneous pregnancies (n = 81). At least 20 GTG-banded metaphases were analyzed in each case for cytogenetic analyses. Statistical analyses were performed using NCSS 2007 Statistical Program software. The significance level and confidence interval for all analyses were set to p < 0.05 and a 95% confidence interval, respectively. RESULTS: A total of 49.3% (75/152) of the miscarriages were cytogenetically abnormal among the patients. We detected cytogenetically abnormalities in 47.9% (34/71) of the ICSI group and 50.6% (41/81) of the control group, which were not statistically significant differences (p=NS). The sex chromosome abnormalities were similar between the ICSI and control groups (p=NS). The most prevalent abnormalities that were observed in the ICSI and control groups with first-trimester pregnancy loss were trisomy (n = 42; 27.6%), Turner syndrome (45, X0, n = 13; 8.6%), triploidy (n = 13; 8.6%), 48 chromosomes (n = 5; 3.3%), and mixed chromosomal abnormalities (n = 3; 1.2%). In addition, the karyotypes were similar between the ICSI and control groups (p=NS). We observed increases in fetal aneuploidy rates with increased maternal age (<30 years = 23.9% vs. 31-34 years = 37.0% vs. 35-39 years = 82.9% vs. >39 years = 90.9%). However, the observed increases in fetal aneuploidy rates were not statistically significant (p=NS). CONCLUSION: The aneuploidy rates and sex chromosome anomalies following ICSI for non-male factor were similar to those following natural conception. PMID- 22038382 TI - Novel iron-sulfur containing NADPH-reductase from Nocardia farcinica IFM10152 and fusion construction with CYP51 lanosterol demethylase. AB - CYP51, a sterol 14alpha-demethylase, is one of the key enzymes involved in sterol biosynthesis and requires electrons transferred from its redox partners. A unique CYP51 from Nocardia farcinica IFM10152 forms a distinct cluster with iron-sulfur containing NADPH-P450 reductase (FprD) downstream of CYP51. Previously, sequence alignment of nine reductases from N. farcinica revealed that FprC, FprD, and FprH have an additional sequence at their N-termini that has very high identity with iron-sulfur clustered ferredoxin G (FdxG). To construct an artificial self sufficient cytochrome P450 monooxygenase (CYP) with only FprD, CYP51, and iron sulfur containing FprD were fused together with designed linker sequences. CYP51 FprD fusion enzymes showed distinct spectral properties of both flavoprotein and CYP. CYP51-FprD F1 and F2 in recombinant Escherichia coli BL21(DE3) catalyzed demethylation of lanosterol more efficiently, with k(cat) /K(m) values of 96.91 and 105.79 nmol/min/nmol, respectively, which are about 35-fold higher compared to those of CYP51 and FprD alone. PMID- 22038383 TI - [Assessment of psychological consequences of trauma]. AB - After accidents psychological consequences are often asserted. This may be due to the traumatic experience itself, the experience of severe physical injury or to the experience of a traumatic hospital treatment. The pivotal point of the medicolegal assessment is the evidence of primary mental or physical damage that has to be documented beyond a reasonable doubt in all areas of law. A medicolegal assessment in five steps is proposed. PMID- 22038384 TI - [Personalized psychiatry and psychotherapy. Realistic hope for the future or fiction?]. PMID- 22038385 TI - [Neuroimaging markers: their role for differential diagnosis and therapeutic decisions in personalized psychiatry]. AB - In the context of personalized psychiatry there is growing interest in the development of neuroimaging markers for differential diagnosis and individualized therapy of mental disorders. This article reports on new neuroimaging markers for the diagnosis of Alzheimer's disease and particularly recent multi-functional magnetic resonance imaging (m-fMRI) studies in patients with schizophrenic and affective psychoses. Using experimental key paradigms for targeted assessment of pathophysiologically relevant neurofunctional systems, these studies reveal both differences and commonalities between the diagnostic categories. In addition, the article outlines research strategies for further development of the classification of major psychoses on the basis of a more precise characterization of the neurofunctional and pathophysiological phenotype. Multivariate approaches may help to identify more complex neuroimaging markers relevant for diagnosis and/or prognosis. Finally, some examples will be presented for the use of neuroimaging markers in the individualized choice of therapy. PMID- 22038386 TI - [Multiple sclerosis management system 3D. Moving from documentation towards management of patients]. AB - BACKGROUND: The increasing therapeutic options for relapsing-remitting multiple sclerosis require a specific treatment and risk management to recognize the individual response as well as potential side effects. To switch from pure MS documentation to MS management by implementing a new multiple sclerosis management and documentation tool may be of importance. METHOD: This article presents the novel computer-based patient management system "multiple sclerosis management system 3D" (MSDS 3D). RESULTS: MSDS 3D allows documentation and visualization of visit schedules and mandatory examinations via defined study modules by integration of data input from patients, attending physicians and MS nurses. It provides forms for the documentation of patient visits as well as clinical and diagnostic findings. Information is collected via interactive touch screens. A specific module which is part of MSDS 3D's current version allows the monthly monitoring of patients under treatment with natalizumab. A checklist covering clinical signs of progressive multifocal leukoencephalopathy (PML) and a detailed questionnaire about the handling of natalizumab in practice have additionally been added. DISCUSSION: The MS patient management system MSDS 3D has successfully been implemented and is currently being evaluated in a multi-centre setting. Advanced assessment of patient data may allow improvements in clinical practice and research work. The addition of a checklist and a questionnaire into the natalizumab module may support the recognition of PML during its early, treatable course. PMID- 22038387 TI - [Alemtuzumab: a further option for treatment of multiple sclerosis]. AB - Alemtuzumab is a humanized monoclonal therapeutic antibody that targets the CD52 antigen which s expressed on most cells of the lymphoid lineage, exclusive of precursors. Alemtuzumab rapidly depletes CD52(+) cells from the peripheral blood. This depletion is long-lasting, and cells repopulate in a specific pattern with B cells and regulatory T cells peaking first. Alemtuzumab was examined for clinical utility in two open-labelled intervention trials in multiple sclerosis (MS). Because of very promising results its clinical efficacy was further explored in a clinical phase-II trial using s.c. interferon beta-1a as the active comparator. Severe or opportunistic infections were surprisingly rare given the long-term lymphopenia. However, up to 30% of patients developed some antibody-mediated autoimmunity. The thyroid gland was the most frequently affected organ. Immune mediated thrombocytopenic purpura and Goodpasture's syndrome were additionally observed. This review summarizes the pre-clinical and clinical development of alemtuzumab and discusses potential modes of action as well as the pathogenetic link to the treatment emergent autoimmune phenomena. PMID- 22038388 TI - [Therapeutic strategies in stroke aftercare. Contents and effects]. AB - No generally accepted guidelines for stroke aftercare exist in Germany. This literature review summarizes the current evidence regarding the content and the effectiveness of aftercare strategies (exercise therapy, physiotherapy, occupational therapy) and their specific dose (intensity, duration, frequency). Exercise therapy (inter alia physiotherapy, resistance, endurance and gait training) has been shown to be effective for improving physical performance (strength, cardiopulmonary fitness, motor function) resulting in beneficial effects on gait, mobility and activities of daily living (ADL). As for the restoration of ADL and the resumption of social and leisure activities occupational therapy proved to be particularly effective. More research is needed to identify the specific effects of different aftercare strategies and their dose response relationship to provide physicians a better foundation for therapy prescriptions. PMID- 22038389 TI - Clinical feasibility study for detection of myocardial oedema by a cine SSFP sequence in comparison to a conventional T2-weighted sequence. AB - BACKGROUND: Cardiovascular magnetic resonance (CMR) T2-imaging is oedema sensitive and can detect increased myocardial water content to potentially distinguish acute from chronic myocardial infarction (AMI/CMI). Currently applied conventional black-blood T2-weighted-turbo-spin-echo (T2-BB-TSE)-sequences cause various artefacts which limit their image quality and possibly hamper their interpretation. Image contrast of conventional cine steady-state free precession (SSFP)-sequences partly consists of T2 oedema-sensitive information. We therefore sought to prospectively evaluate SSFP cine-imaging to detect myocardial oedema and differentiate AMI from CMI. METHODS: We examined 60 patients with AMI, 30 patients with CMI and 30 healthy volunteers using a 1.5 Tesla-MR whole body scanner. In a blinded fashion, myocardial oedema was assessed with T2-BB-TSE and SSFP-sequences, late gadolinium contrast-enhanced (LGE) CMR images being deemed as the standard reference for identification of infarcted myocardium. Assessment of presence of CMR detectable myocardial oedema was performed visually and quantitatively. P < 0.05 was considered statistically significant. RESULTS: The contrast-to-noise ratio (CNR) in AMI patients was significantly higher (SSFP STEMI and SSFP-NSTEMI: 19 +/- 12 and 20 +/- 14; T2-BB-TSE STEMI and T2-BB-TSE NSTEMI: 33 +/- 16 and 31 +/- 13) than in CMI for both MR-sequences (SSFP-STEMI and NSTEMI: 3.5 +/- 1.5 and T2-BB-TSE:9.3 +/- 9.6, p for all <0.001). By visual analysis, SSFP images achieved a sensitivity of 96%, a specificity of 87%, positive and negative predictive values of 95 and 92% when compared to the existence of gadolinium contrast-enhanced scar imaging. Similarly, for T2-BB-TSE, sensitivity and specificity were 93 and 83% with positive and negative predictive values of 92 and 90%. Inter-observer variability was 0.90 for SSFP and 0.83 for T2-BB-TSE images. CONCLUSION: A standard clinical SSFP sequence is not inferior to T2-BB-TSE for the detection of myocardial oedema and can be used to reliably distinguish AMI from CMI. Especially in patients with insufficient T2-BB-TSE image quality, the SSFP sequence may be an alternative for the detection of myocardial oedema. PMID- 22038390 TI - The interference of introversion-extraversion and depressive symptomatology with reasoning performance: a behavioural study. AB - The objective of this study was to investigate the link between the Eysenck Personality Questionnaire (EPQ) scores and depressive symptomatology with reasoning performance induced by a task including valid and invalid Aristotelian syllogisms. The EPQ and the Zung Depressive Scale (ZDS) were completed by 48 healthy subjects (27 male, 21 female) aged 33.5 +/- 9.0 years. Additionally, the subjects engaged into two reasoning tasks (valid vs. invalid syllogisms). Analysis showed that the judgment of invalid syllogisms is a more difficult task than of valid judgments (65.1% vs. 74.6% of correct judgments respectively, p < 0.01). In both conditions, the subjects' degree of confidence is significantly higher when they make a correct judgment than when they make an incorrect judgment (83.8 +/- 11.2 vs. 75.3 +/- 17.3, p < 0.01). Subjects with extraversion as measured by EPQ and high sexual desire as rated by the relative ZDS subscale are more prone to make incorrect judgments in the valid syllogisms, while, at the same time, they are more confident in their responses. The effects of extraversion/introversion and sexual desire on the outcome measures of the valid condition are not commutative but additive. These findings indicate that extraversion/introversion and sexual desire variations may have a detrimental effect in the reasoning performance. PMID- 22038391 TI - Design, synthesis, and application of tartaric acid derived N-spiro quaternary ammonium salts as chiral phase-transfer catalysts. AB - A novel class of tartaric acid-derived N-spiro quaternary ammonium salts was synthesised starting from known TADDOLs. These compounds were found to catalyse the asymmetric alpha-alkylation of glycine Schiff bases with high enantioselectivities and in good yields. PMID- 22038392 TI - Quality of life of community-residing persons with dementia based on self-rated and caregiver-rated measures. AB - PURPOSE: To identify correlates of self-rated and caregiver-rated quality of life (QOL) in community-residing persons with dementia (PWD) for intervention development. METHODS: Cross-sectional data of 254 PWD and their caregivers participating in a clinical trial were derived from in-home assessments. Self rated QOL was measured with the Quality of Life-Alzheimer Disease (QOL-AD) scale, and caregiver-rated QOL was measured using the QOL-AD and Alzheimer Disease Related Quality of Life (ADRQL) scales. Multivariate modeling identified correlates of the PWD' QOL. RESULTS: Self-rated QOL was related significantly to participant race, unmet needs, depression, and total medications. Caregiver-rated QOL-AD scores were significantly associated with participant function, unmet needs, depression, and health problems and with caregiver burden and self-rated health. Significant correlates of ADRQL scores included neuropsychiatric symptom severity, functional and cognitive impairment, and caregiver burden and depression. CONCLUSIONS: Correlates of QOL in community-residing PWD depend on who rates the PWD's QOL and which measure is used. Addressing health problems, medication use, and dementia-related unmet needs, reducing functional dependency, and treating neuropsychiatric symptoms in PWD, while reducing caregiver burden and depression, may maximize QOL in those with dementia. PMID- 22038393 TI - The impact of denial on health-related quality of life in patients with HIV. AB - BACKGROUND/PURPOSE: The purpose of this study was to examine the influence of denial coping on quality of life (QOL) over time among individuals living with HIV, as denial has been understudied as a coping strategy within the literature on HIV/AIDS. METHODS: In a sample of 65 adult men and women, we used multilevel linear modeling to test trajectories of change in physical and mental health related QOL across baseline, 3, 6, and 12 months, including denial as a predictor and gender as a moderator. RESULTS: The use of denial coping was associated with lower physical and mental health-related QOL at baseline. Denial coping predicted an increase in QOL over time, though QOL remained low in those who practiced denial coping. Men's baseline mental health-related QOL was more negatively affected by denial coping than women's. Women tended to increase in QOL more slowly over time compared to men. CONCLUSION: Reliance on denial as a coping strategy is associated with poorer physical and mental health-related QOL in an HIV-positive population, though participants who engaged in denial also displayed more rapid improvement in their QOL over time. Men and women displayed different rates of improvement in QOL, indicating a need for gender-based treatment approaches. Future research should examine the complex role of denial on change in QOL. PMID- 22038394 TI - Association between adherence to physical activity guidelines and health-related quality of life among individuals with physician-diagnosed arthritis. AB - PURPOSE: To examine the association between adherence to physical activity guidelines and health-related quality of life (HRQOL) among individuals with arthritis. METHODS: A cross-sectional sample with 33,071 US adults, 45 years or older with physician-diagnosed arthritis was obtained from 2007 Behavioral Risk Factor Surveillance System survey. We conducted negative binomial regression analysis to examine HRQOL as a function of adherence to physical activity guidelines controlling for physicians' recommendations for physical activity, age, sex, race, education, marital status, employment, annual income, health insurance, personal physician, emotional support, body mass index, activity limitations, health status, and co-morbidities based on Behavioral Model of Health Services Utilization. RESULTS: Descriptive statistics showed that 60% adults with arthritis did not adhere to physical activity guidelines, mean physically and mentally unhealthy days were 7.7 and 4.4 days, respectively. Results from negative binomial regression indicated that individuals who did not adhere to physical activity guidelines had 1.14 days more physically unhealthy days and 1.12 days more mentally unhealthy days than those who adhered controlling for covariates. CONCLUSIONS: Adherence to physical activity is important to improve HRQOL for individuals with arthritis. However, adherence is low among this population. Interventions are required to engage individuals with arthritis in physical activity. PMID- 22038395 TI - Donna Lamping (1953-2011). PMID- 22038396 TI - Mental quality of life in chronic fatigue is associated with an accommodative coping style and neuroticism: a path analysis. AB - PURPOSE: An accommodative coping style (e.g. acceptance) is related to a better mental health-related quality of life (MHQL) in patients with chronic fatigue syndrome (CFS). We want to explore whether neuroticism is predictive for this coping style and MHQL. Secondly we want to explore the relation between acceptance and physical health-related quality of life (PHQL) and expect that illness-related variables such as fatigue severity and duration are related to PHQL. METHOD: In this cross-sectional study, 117 patients with chronic fatigue syndrome from an outpatient internal medicine clinic completed self-report questionnaires on quality of life (SF-36), acceptance (ICQ), personality traits (NEO-FFI) and fatigue severity (CIS). RESULTS: Regression analyses showed that neuroticism and acceptance are predictors of MHQL (38% of the variance was explained). The path analysis showed that acceptance mediates between neuroticism and MHQL and that PHQL is related to MHQL. PHQL is related to fatigue severity and duration, but not to neuroticism and acceptance. CONCLUSION: Stimulating an 'accepting accommodative coping style' within the treatment for CFS is important in improving mental quality of life. Our results suggest that neuroticism may be negatively related to acceptance and MHQL. This findings support the idea that a psychological diagnostic workout with special attention to personality traits in relation to their coping style is recommended in order to choose the most appropriate therapeutic approach in this population. PMID- 22038397 TI - Characteristics and quality of pediatric cost-utility analyses. AB - PURPOSE: Measuring utility for cost-utility analysis (CUA) is challenging in children. The objectives were to characterize pediatric CUAs, appraise their quality, and identify determinants of higher quality. METHODS: Descriptive data were imported from the PEDE database for 305 pediatric CUAs published from 1997 to 2009, and quality was rated using the Pediatric Quality Appraisal Questionnaire (PQAQ) in 213 studies. The impact on quality of publication year, journal type, and whether utility was measured was analyzed using multiple regression. RESULTS: CUAs increased over time and the largest proportion was from North America (38%). Children aged 1-12 years (39%) and preventative interventions (51%) were studied most frequently. Whereas a societal perspective was most common in papers published before 2007 (49%), a third-party payer perspective was subsequently most frequent (63%). Utility was measured prospectively in 8% of studies. Domains that demonstrated the poorest quality were Perspective, Costs and resource use, Outcomes, Analysis, Incremental analysis and Conflict of interest. Quality increased significantly over time for most domains and was greater in studies published in methods/health economic journals. CONCLUSIONS: The quality of pediatric CUAs is increasing. Few studies ascertain utility prospectively, suggesting the need for better instruments for pediatric health state valuation and measurement. PMID- 22038398 TI - Roles of the PI3K/Akt pathway and autophagy in TLR3 signaling-induced apoptosis and growth arrest of human prostate cancer cells. AB - Toll-like receptors (TLRs) are widely expressed in immune cells and play a crucial role in many aspects of the immune response. Although some types of TLRs are also expressed in cancer cells, the effects and mechanisms of TLR signaling in cancer cells have not yet been fully elucidated. In the present study, we analyzed the effects of polyinosinic-polycytidylic acid [poly(I:C)], a TLR3 ligand, on three TLR3-expressing human prostate cancer cell lines (LNCaP, PC3, and DU145). We then further characterized the underlying mechanisms, focusing on the poly(I:C)-sensitive LNCaP cell line. Poly(I:C) significantly reduced the viability of LNCaP cells TLR3 and endosome dependently. One mechanism for the antitumor effect was caspase-dependent apoptosis, and another mechanism was poly(I:C)-induced growth arrest. Cell survival and proliferation of LNCaP cells depended on the PI3K/Akt pathway, and PI3K/Akt inhibitors induced apoptosis and growth arrest similar to poly(I:C) treatment. Additionally, poly(I:C) treatment caused dephosphorylation of Akt in LNCaP cells, but transduction of the constitutively active form of Akt rendered LNCaP cells resistant to poly(I:C). Immunoblot analysis of proliferation- and apoptosis-related molecules in poly(I:C)-treated LNCaP cells revealed participation of cyclinD1, c-Myc, p53, and NOXA. Interestingly, poly(I:C) treatment of LNCaP cells was accompanied by autophagy, which was cytoprotective toward poly(I:C)-induced apoptosis. Together, these findings indicate that TLR3 signaling triggers apoptosis and growth arrest of LNCaP cells partially through inactivation of the PI3K/Akt pathway and that treatment-associated autophagy plays a cytoprotective role. PMID- 22038400 TI - (-)-Epigallocatechin-3-gallate protects against neuronal cell death and improves cerebral function after traumatic brain injury in rats. AB - A major component of green tea, a widely consumed beverage, is (-) epigallocatechin gallate (EGCG), which has strong antioxidant properties. Our previous study has indicated that free radical production following rat traumatic brain injury (TBI) induces neural degeneration. In this study, we investigated the effects of EGCG on cerebral function and morphology following TBI. Six-week old male Wistar rats that had access to normal drinking water, or water containing 0.1% (w/v) EGCG ad libitum, received TBI with a pneumatic controlled injury device at 10 weeks of age. Immunohistochemistry and lipid peroxidation studies revealed that at 1, 3 and 7 days post-TBI, the number of 8-hydroxy-2' deoxyguanosine-, 4-hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells, and the levels of malondialdehyde (MDA) around the damaged area after TBI, significantly decreased in the EGCG treatment group compared with the water group (P < 0.05). Most ssDNA-positive cells in the water group co-localized with neuronal cells. However, in the EGCG treatment group, few ssDNA-positive cells co localized with neurons. In addition, there was a significant increase in the number of surviving neuronal cells and an improvement in cerebral dysfunction after TBI in the EGCG treatment group compared with the water group (P < 0.05). These results indicate that consumption of water containing EGCG pre- and post TBI inhibits free radical-induced neuronal degeneration and apoptotic cell death around the damaged area, resulting in the improvement of cerebral function following TBI. In summary, consumption of green tea may be an effective therapy for TBI patients. PMID- 22038401 TI - Mass sensors with mechanical traps for weighing single cells in different fluids. AB - We present two methods by which single cells can be mechanically trapped and continuously monitored within the suspended microchannel resonator (SMR) mass sensor. Since the fluid surrounding the trapped cell can be quickly and completely replaced on demand, our methods are well suited for measuring changes in cell size and growth in response to drugs or other chemical stimuli. We validate our methods by measuring the density of single polystyrene beads and Saccharomyces cerevisiae yeast cells with a precision of approximately 10(-3) g cm(-3), and by monitoring the growth of single mouse lymphoblast cells before and after drug treatment. PMID- 22038402 TI - Static versus dynamic gerbil tympanic membrane elasticity: derivation of the complex modulus. AB - An accurate estimation of tympanic membrane stiffness is important for realistic modelling of middle ear mechanics. Tympanic membrane stiffness has been investigated extensively under either quasi-static or dynamic loading conditions. It is known that biological tissues are sensitive to strain rate. Therefore, in this work, the mechanical behaviour of the tympanic membrane was studied under both quasi-static and dynamic loading conditions. Experiments were performed on the pars tensa of four gerbil tympanic membranes. A custom-built indentation apparatus was used to perform in situ tissue indentations and testing was done applying both quasi-static and dynamic sinusoidal indentations up to 8.2 Hz. The unloaded shape of the tympanic membrane was measured and used to create specimen specific finite element models to simulate the experiments. The frequency dependent Young's modulus of each specimen was then estimated by an inverse analysis in which the error between experimental and simulated indentation data was optimised for each indentation frequency separately. Using an 8 MUm central region thickness, we found Young's moduli between 71 and 106 MPa (n = 4) at 0.2 Hz indentation frequency. A standard linear viscoelastic model and a viscoelastic model with a continuous relaxation spectrum were used to derive a complex modulus in the frequency domain. Due to experimental limitations, the indentation frequency upper limit was 8.2 Hz. The average relative modulus increase in this domain was 14% and the increase was the strongest below 6 Hz. PMID- 22038403 TI - The response of T cells to interleukin-6 is differentially regulated by the microenvironment of the rheumatoid synovial fluid and tissue. AB - OBJECTIVE: Interleukin-6 (IL-6) is a proinflammatory cytokine with regulatory effects on the survival and differentiation of T cells. It exerts its biologic function in 2 ways: by directly binding to the IL-6 receptor (IL-6R; CD126) or via trans-signaling, in which soluble IL-6R/IL-6 complexes bind to the signaling component CD130. This study was undertaken to assess the expression and regulation of CD126 and CD130 and determine how these affect the response of CD4+ T cells to IL-6 in the joints of patients with rheumatoid arthritis (RA). METHODS: Flow cytometry and immunofluorescence microscopy were used to determine the expression, function, and regulation of CD126 and CD130 in CD4+ T cells from the peripheral blood (PB), synovial fluid (SF), and synovial tissue of RA patients. RESULTS: Compared to the findings in RA PB, CD4+ T cells in the SF and synovial tissue expressed low levels of CD126. In contrast, whereas CD4+ T cell expression of CD130 was minimal in the SF, its level in the synovial tissue was high. Consistent with this phenotype, synovial tissue T cells responded to trans signaling by soluble IL-6R/IL-6 complexes, whereas no response was evident in CD4+ T cells from the SF. Down-regulation of both receptor components in SF T cells could be explained by exposure to high levels of IL-6. Increased levels of CD130 messenger RNA and protein in synovial tissue CD4+ T cells suggested that CD130 is up-regulated locally. Among a range of cytokines tested, only IL-10 induced CD130 expression in T cells. CONCLUSION: The inflamed microenvironment in the synovial tissue maintains responsiveness to IL-6 trans-signaling through the up-regulation of CD130 expression in CD4+ T cells, and this process may be driven by IL-10. PMID- 22038404 TI - Molecular signature of a public clonotypic autoantibody in primary Sjogren's syndrome: a "forbidden" clone in systemic autoimmunity. AB - OBJECTIVE: This study was undertaken to determine the molecular characteristics of clonotypic autoantibodies in the sera of patients with primary Sjogren's syndrome (SS). This characterization is hampered by the presence of mixed anti Ro/La specificities that may conceal clonotypic species. In order to narrow clonotypic diversity, a positive selection step was performed on a peg-like determinant of Ro 60 (termed Ro 60-peg) prior to analysis of the autoantibody proteome. METHODS: Monospecific anti-Ro 60-peg IgG were isolated by affinity purification from the sera of 7 patients with primary SS and anti-Ro/La and subjected to 2-dimensional gel electrophoresis and high-resolution orbitrap mass spectrometric sequencing. V regions of heavy and light chains were analyzed by combined database and de novo amino acid sequencing. RESULTS: Proteomic analysis revealed a Ro 60-peg-specific IgG1kappa-restricted monoclonal autoantibody that was present in the sera of all patients and specified by a V(H) 3-23 heavy chain paired with a V(kappa) 3-20 light chain. The public anti-Ro 60-peg clonotype was specified further by common mutations in the heavy-chain and light-chain complementarity-determining regions. Titers and relative affinities of clonotypic IgG did not vary over the course of the disease. CONCLUSION: The expression of a Ro 60-reactive public B cell clonotype in a subset of patients with primary SS as a long-lived, class-switched circulating autoantibody implies a common breach of B cell tolerance checkpoints in these patients. The unique heavy chain/light chain signature opens the possibility of tracking the development of a "forbidden" clone against a bona fide systemic autoantigen in human disease. PMID- 22038405 TI - Copy number variations of interleukin-17F, interleukin-21, and interleukin-22 are associated with systemic lupus erythematosus. AB - OBJECTIVE: Systemic lupus erythematosus (SLE) represents the classic prototype of systemic autoimmune disease. The identification of the Th17 cell subset has provided new understanding regarding the underlying mechanisms of autoimmunity. Copy number variations (CNVS) have been discovered to have phenotypic consequences and are associated with various types of diseases. We undertook this study to explore a possible association between CNVS of Th17 cell-related genes and the risk of SLE. METHODS: We extracted genomic DNA and RNA from 938 SLE patients and 1,017 healthy controls. We examined CNVS of Th17 cell-related genes, including retinoic acid receptor-related orphan nuclear receptor gammat, STAT-3, interleukin-6 (IL-6), transforming growth factor beta, tumor necrosis factor alpha, IL-17A, IL-17F, IL-21, IL-22, IL-23A, CCL20, and CCR6, and levels of messenger RNA (mRNA) for IL-17F, IL-21, and IL-22. RESULTS: Genotype and allele frequencies for copy number amplifications of IL-17F, IL-21, and IL-22 were found to be significantly higher in SLE patients than in healthy controls. CNVS of IL 17F, IL-21, and IL-22 had no synergistic contribution to SLE. The mRNA expression of IL-17F, IL-21, and IL-22 in the samples with >2 copies of DNA was significantly higher than that in those with 2 copies of DNA. CONCLUSION: Our findings indicate that CNVS of IL-17F, IL-21, and IL-22 are associated with the risk of SLE. PMID- 22038406 TI - Primary central nervous system vasculitis presenting with intracranial hemorrhage. AB - OBJECTIVE: To describe a subset of cases in a large retrospectively identified cohort of patients with primary central nervous system vasculitis (PCNSV) who present with intracranial hemorrhage. METHODS: The study consisted of a cohort of 131 consecutive patients with PCNSV who were seen at the Mayo Clinic over a 25 year period from 1983 to 2007. The diagnosis of PCNSV was based on findings of brain or spinal cord biopsy, cerebral angiography, or both. Intracranial hemorrhage at presentation was defined as the presence of intracerebral or subarachnoid hemorrhage on computed tomography or magnetic resonance imaging (MRI) of the brain within 3 months of the date of PCNSV diagnosis. The clinical, laboratory, radiologic, and pathologic findings, therapy, and outcomes in patients presenting with intracranial hemorrhage were compared with those without intracranial hemorrhage. RESULTS: Sixteen patients (12.2%) had evidence of intracranial hemorrhage at or near the time of diagnosis. Twelve patients had intracerebral hemorrhage, and 4 had subarachnoid hemorrhage. Twelve patients were diagnosed by findings on angiography and 4 by findings on CNS biopsy. Compared with the 115 patients without intracranial hemorrhage, the 16 patients presenting with intracranial hemorrhage were more frequently women, less frequently had altered cognition, a persistent neurologic deficit, or stroke at presentation, less frequently had MRI evidence of cerebral infarctions, and less frequently needed therapy at last followup. A necrotizing histopathologic pattern of vasculitis was observed in 3 of the 4 patients with positive biopsy findings (75%). CONCLUSION: Our findings suggest that intracranial hemorrhage may not be an infrequent occurrence in early PCNSV. Necrotizing vasculitis may be a predominant histopathologic pattern. PMID- 22038407 TI - Clinical images: cutaneous necrotizing vasculitis in a patient with lepromatous leprosy. PMID- 22038411 TI - Applications of plant viruses in bionanotechnology. AB - The capsids of most plant viruses are simple and robust structures consisting of multiple copies of one or a few types of protein subunit arranged with either icosahedral or helical symmetry. In many cases, capsids can be produced in large quantities either by the infection of plants or by the expression of the subunit(s) in a variety of heterologous systems. In view of their relative simplicity, stability and ease of production, plant virus particles or virus-like particles (VLPs) have attracted attention as potential reagents for applications in bionanotechnology. As a result, plant virus particles have been subjected to both genetic and chemical modification, have been used to encapsulate foreign material and have, themselves, been incorporated into supramolecular structures. PMID- 22038410 TI - Sexual, behavioral, and quality of life characteristics of healthy weight, overweight, and obese gay and bisexual men: findings from a prospective cohort study. AB - While there have been attempts to explore the association of obesity and risky sexual behaviors among gay men, findings have been conflicting. Using a prospective cohort of gay and bisexual men residing in Pittsburgh, we performed a semi-parametric, group-based analysis to identify distinct groups of trajectories in body mass index slopes over time from 1999 to 2007 and then correlated these trajectories with a number of psychosocial and behavioral factors, including sexual behaviors. We found many men were either overweight (41.2%) or obese (10.9%) in 1999 and remained stable at these levels over time, in contrast to recent increasing trends in the general population. Correlates of obesity in our study replicated findings from the general population. However, we found no significant association between obesity and sexual risk-taking behaviors, as suggested from several cross-sectional studies of gay men. While there was not a significant association between obesity and sexual risk-taking behaviors, we found high prevalence of overweight and obesity in this population. Gay and bisexual men's health researchers and practitioners need to look beyond HIV and STI prevention and also address a broader range of health concerns important to this population. PMID- 22038412 TI - Virus-derived ssDNA vectors for the expression of foreign proteins in plants. AB - Plant viruses with ssRNA genomes provide a unique opportunity for generating expression vehicles for biopharming in plants, as constructs containing only the replication origin, with the replication-associated protein (Rep) gene provided in cis or in trans, can be replicationally amplified in vivo by several orders of magnitude, with significant accompanying increases in transcription and expression of gene(s) of interest. Appropriate replicating vectors or replicons may be derived from several different generic geminiviruses (family Geminiviridae) or nanoviruses (family Nanoviridae), for potential expression of a wide range of single or even multiple products in a wide range of plant families. The use of vacuum or other infiltration of whole plants by Agrobacterium tumefaciens suspensions has allowed the development of a set of expression vectors that rival the deconstructed RNA virus vectors in their yield and application, with some potential advantages over the latter that still need to be explored. Several modern applications of ssDNA plant vectors and their future potential will be discussed. PMID- 22038414 TI - Bariatric surgery outcomes in the elderly: an ACS NSQIP study. AB - INTRODUCTION: Mortality and complications following bariatric surgery occur at acceptable rates, but its safety in the elderly population is unknown. We hypothesized that short-term operative outcomes in bariatric surgery patients >=65 years would be comparable to younger persons. METHODS: Patients with a body mass index >=35 kg/m(2) who underwent bariatric surgery in the 2005-2009 American College of Surgeons National Surgical Quality Improvement Program were identified. Controlling for confounders, multivariate regression was used to predict the impact of age on mortality, major events and prolonged length of stay at 30 days. RESULTS: We identified 48,378 patients who underwent bariatric procedures between 2005 and 2009. Multivariate regression analysis demonstrated advancing age trended towards predicting mortality, but was not statistically significant. Additionally, patients >=65 years did not experience higher risk of major complications for either open or laparoscopic procedures. However, patients age >=65 years were more likely to experience prolonged length of stay for both open and laparoscopic procedures. CONCLUSION: This multi-hospital study demonstrates older age predicts short-term prolonged length of stay but not major events following bariatric surgery. Older age trends toward predicting mortality, but it is not statistically significant. PMID- 22038415 TI - Tanshinone IIA induces growth inhibition and apoptosis in gastric cancer in vitro and in vivo. AB - As a phytochemical derived from the roots of Salvia miltiorrhiza Bunge, Tanshinone IIA has been reported to possess anti-inflammatory and antioxidant activity. Studies in breast, colon, prostate and lung cancer indicate that Tanshinone IIA may exhibit a promising antitumor activity. However, systemic studies of the cytotoxic effects of Tanshinone IIA on gastric cancer have not been described. The present study offers a comprehensive evaluation of the antitumor effects of Tanshinone IIA in gastric cancer cells in vitro and in a mouse xenograft model. Cell viability and apoptosis in vitro were evaluated through the MTT assay and flow cytometry analysis. The results indicate that Tanshinone IIA can induce gastric cancer cell growth inhibition and apoptosis in a time- and concentration-dependent manner. Furthermore, we investigated the mechanism of the apoptotic effects induced by Tanshinone IIA. We found that Tanshinone IIA can not only cause cell cycle arrest in the G2/M phase, but also trigger the intrinsic apoptotic signaling pathway. The results suggest that Tanshinone IIA may serve as an effective adjunctive reagent in the treatment of gastric cancer. PMID- 22038416 TI - Carboxylator: incorporating solvent-accessible surface area for identifying protein carboxylation sites. AB - In proteins, glutamate (Glu) residues are transformed into gamma-carboxyglutamate (Gla) residues in a process called carboxylation. The process of protein carboxylation catalyzed by gamma-glutamyl carboxylase is deemed to be important due to its involvement in biological processes such as blood clotting cascade and bone growth. There is an increasing interest within the scientific community to identify protein carboxylation sites. However, experimental identification of carboxylation sites via mass spectrometry-based methods is observed to be expensive, time-consuming, and labor-intensive. Thus, we were motivated to design a computational method for identifying protein carboxylation sites. This work aims to investigate the protein carboxylation by considering the composition of amino acids that surround modification sites. With the implication of a modified residue prefers to be accessible on the surface of a protein, the solvent accessible surface area (ASA) around carboxylation sites is also investigated. Radial basis function network is then employed to build a predictive model using various features for identifying carboxylation sites. Based on a five-fold cross validation evaluation, a predictive model trained using the combined features of amino acid sequence (AA20D), amino acid composition, and ASA, yields the highest accuracy at 0.874. Furthermore, an independent test done involving data not included in the cross-validation process indicates that in silico identification is a feasible means of preliminary analysis. Additionally, the predictive method presented in this work is implemented as Carboxylator ( http://csb.cse.yzu.edu.tw/Carboxylator/ ), a web-based tool for identifying carboxylated proteins with modification sites in order to help users in investigating gamma-glutamyl carboxylation. PMID- 22038417 TI - Microscopy and proteomic analysis of the non-host resistance of Oryza sativa to the wheat leaf rust fungus, Puccinia triticina f. sp. tritici. AB - Rice (Oryza sativa) cv. Nipponbare expresses non-host resistance (NHR) to the wheat leaf rust fungus, Puccinia triticina f. sp. tritici (Ptt). When the leaves of cv. Nipponbare were inoculated with Ptt, approx 93% of the urediniospores germinated on the leaf surface, but only 10% of the germinated spores formed appressoria over the stomata at one day post inoculation (1 dpi). Hydrogen peroxide (H(2)O(2)) accumulated in host cells around the appressoria at 3 dpi. Approx. 3% of the appressoria produced short hyphae inside the leaf, and fluorescence was observed in tissue invaded by the hyphae by 7 dpi. At 22 dpi, 0.2% of the sites with appressoria formed branching infection hypha in mesophyll cells, but no substomatal vesicles, haustorial mother cells or haustoria were observed. Proteins were extracted from leaves 3 dpi and analyzed by two dimensional gel electrophoresis (2-DE). A total 33 spots were reproducibly up regulated and 9 were down-regulated by infection compared to the water inoculated control. Of these, 30 were identified by MALDI-TOF Mass Spectrometry. The identified proteins participate in defense/stress responses, energy/carbohydrate metabolism, oxidation-reduction processes, protein folding/turnover/cleavage/degradation, signal transduction and cell death regulation. The results indicates that NHR of rice to Ptt is consistent with a shift in protein and energy metabolism, increased antimicrobial activities, possibly including phytoalexin accumulation and cell wall reinforcement, increased cell repair, antioxidive and detoxification reactions, and enhanced prevention of plant cell death. Nearly half of the up-regulated identified proteins were associated with chloroplast and mitochondrial physiology suggesting important roles for these organelles during NHR. PMID- 22038418 TI - [Intestinal microbiota as regulator of the immune system]. AB - The intestinal microbiota contributes to the regulation of the intestinal immune system and protection against intestinal infections. Recent studies revealed that the locally restricted intestinal microbiota affects systemic immunity and influences the induction of autoimmunity. PMID- 22038419 TI - Algal diversity in flowing waters at an acidic mine drainage "barrens" in central Pennsylvania, USA. AB - Microscopic investigations were undertaken to decipher the diversity in the lotic algal communities from acidic waters (pH 2.4-3.2) flowing overland in sheets and channels at an acid mine drainage (AMD) barrens near Kylertown, PA, USA. Microscopic observations, supplemented with taxonomic keys, aided in identification of the dominant algae, and measurement of carbon from adjacent soils was undertaken. The unicellular protist Euglena sp. was most abundant in slower flowing waters (i.e., pool near point of emergence and surficial flow sheets), while Ulothrix sp. was most abundant in faster flowing water from the central stream channel. A diverse range of unicellular microalgae such as Chlorella, Cylindrocystis, Botryococcus, and Navicula and several filamentous forms identified as Microspora, Cladophora, and Binuclearia were also recorded. The observed high algal diversity may be related to the long duration of AMD flow at this site which has led to the development of adapted algal communities. The comparatively higher carbon content in soil materials adjacent to slower flowing water sampling locations provides evidence for the important role of algae as primary producers in this extreme environment. PMID- 22038420 TI - A qualitative analysis of barriers, challenges, and successes in meeting the needs of Hurricane Katrina evacuee families. AB - Hurricane Katrina caused many individuals to evacuate to towns and cities throughout the United States. Psychological First Aid (PFA) is a treatment program designed to help clinicians and other disaster relief workers address the needs of adults, youth, and families immediately following disasters. We conducted focus groups with disaster relief and evacuee service providers in the Kansas City Metro Area as an exploratory study to identify their perceptions of the needs of evacuees. Participants identified a number of mental health needs, as well as displacement-related challenges, including loss of social support, material loss, unemployment, and other stressful life events that were secondary to the hurricane. Many of these needs are consistent with principles presented in the PFA manual. We also found that service providers faced unique challenges when attempting to assist evacuees. We discuss implications of these findings for treatment programs and provide suggestions for addressing barriers to care. PMID- 22038421 TI - Neuroleptic malignant syndrome during multiple antipsychotic therapy. PMID- 22038422 TI - Consultation liaison psychiatry in Africa -- essential service or unaffordable luxury? PMID- 22038423 TI - HIV as an index stressor for PTSD: challenges and pitfalls in applying DSM criteria. PMID- 22038424 TI - Dynamic psychiatry and the psychodynamic formulation. AB - This article aims to describe the difference between descriptive and dynamic psychiatry. As part of the latter every psychiatrist should be able to construct a psychodynamic formulation. A psychodynamic formulation, an indication of psychological mindedness, helps the psychiatrist to recognize the unique, personal aspects of the illness and the life of the patient. The formulation furthermore helps with the initial orientation towards the patient: it anticipates and predicts how the patient might interact with the psychiatrist and how defenses and underlying conflicts will manifest themselves in treatment. The formulation can therefore be very useful in the treatment of any patient, since it can help to understand and manage the patient's attitude towards being prescribed medication, as well as compliance and prognosis and serve as an initial guide in the psychotherapy. The psychodynamic formulation is unfortunately seldom incorporated in the psychiatric presentation of patients; guidelines are therefore given to especially help psychiatric trainees with the construction of such a formulation. PMID- 22038425 TI - Culture-bound syndromes and the neglect of cultural factors in psychopathologies among Africans. AB - One of the major problems in psychiatric practice worldwide is inability to reach a consensus as regards a globally acceptable classificatory system for the different psychopathologies. Consequently, apart from the WHO's International Classification of Diseases (ICD) that is expected to be universally applicable there are regional-based classificatory systems in some parts of the world. In Africa, a number of culture bound syndromes (CBS) have been described which have not been given international recognition. The possible consequences of this non recognition are highlighted in this paper. Unfortunately there are serious constraints such as the relatively small number of psychiatrists on the continent, and inadequate funding for mental health research, which militate against producing an African classificatory system. Nevertheless, it is proposed that reports of African psychiatrists emanating from their research and clinical experience should be accorded adequate recognition in the WHO so as to assign these CBS their rightful placement in the International classificatory system. PMID- 22038426 TI - Attention deficit hyperactivity disorder symptom self-report among medical students in Eldoret, Kenya. AB - BACKGROUND: To determine the prevalence of self-reported attention deficit hyperactivity disorder (ADHD) symptoms among medical students in Eldoret, Kenya. METHODS: A cross-sectional descriptive study of all medical students who gave consent to participate in the study. Undertaken at Moi University's School of Medicine in Eldoret, Kenya. Comprising two hundred and fifty three (253) undergraduate medical students, with a mean age of 23.7 years (19-42, s.d. 4.1), of whom 51% were female. Measuring ADHD symptomatology using the Adult ADHD Self Report Scale (ASRS v1.1). RESULTS: The prevalence rate of self-reported ADHD symptoms using the ASRS screener was 23.7%. This was significantly associated with being in the age-group 17-20 years compared (p<0.05). The prevalence rate was higher among females (25.6%) than among males (21.8%), but this difference was not statistically significant. Preclinical students had a higher prevalence rate of ADHD symptoms (28.7%) compared to clinical students (19.6%), but this was also not statistically significant. Using a modification of the ASRS full symptom checklist to approximate a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) ADHD diagnosis yielded a 'possible ADHD' prevalence rate of 8.7%. Of these, the inattentive type was the most common (40.9%). CONCLUSION: The prevalence rate of self-reported ADHD symptoms among medical students in Eldoret is very high and possibly interferes with the students' social and academic functioning. Further studies are suggested to generate information on the real ADHD prevalence in the general population and in special populations such as schools and colleges. PMID- 22038427 TI - Attitudes of primary health care providers towards people with mental illness: evidence from two districts in Zambia. AB - OBJECTIVE: The aim of this study was to explore health care providers' attitudes towards people with mental illness within two districts in Zambia. It sought to document types of attitudes of primary health care providers towards people suffering from mental illness and possible predictors of such attitudes. This study offers insights into how health care providers regard people with mental illness that may be helpful in designing appropriate training or re-training programs in Zambia and other low-income African countries. METHOD: Using a pilot tested structured questionnaire, data were collected from a total of 111 respondents from health facilities in the two purposively selected districts in Zambia that the Ministry of Health has earmarked as pilot districts for integrating mental health into primary health care. RESULTS: There are widespread stigmatizing and discriminatory attitudes among primary health care providers toward mental illness and those who suffer from it. These findings confirm and add weight to the results from the few other studies which have been conducted in Africa that have challenged the notion that stigma and discrimination of mental illness is less severe in African countries. CONCLUSION: There is an urgent need to start developing more effective awareness-raising, training and education programmes amongst health care providers. This will only be possible if there is increased consensus, commitment and political will within government to place mental health on the national agenda and secure funding for the sector. These steps are essential if the country is improve the recognition, diagnosis and treatment of mental disorders, and realize the ideals enshrined in the progressive health reforms undertaken over the last decade. PMID- 22038428 TI - Developmental delay of infants and young children with and without fetal alcohol spectrum disorder in the Northern Cape Province, South Africa. AB - OBJECTIVE: To describe the extent and nature of developmental delay at different stages in childhood in a community in South Africa, with a known high rate of Fetal Alcohol Spectrum Disorder (FASD). METHOD: cohort of infants, clinically examined for FASD at two time periods, 7-12 months (N= 392; 45 FASD) and 17-21 months of age (N = 83, 35 FASD) were assessed using the Griffiths Mental Developmental Scales (GMDS). RESULTS: Infants and children with FASD perform worse than their Non-FASD counterparts over all scales and total developmental quotients. Mean quotients for both groups decline between assessments across subscales with a particularly marked decline in the hearing and language scale at Time 2 (scores dropping from 110.6 to 83.1 in the Non-FASD group and 106.3 to 72.7 in the FASD group; P = 0.004). By early childhood the developmental gap between the groups widens with low maternal education, maternal depression, high parity and previous loss of sibling/s influencing development during early childhood. CONCLUSION: The FASD group show more evidence of developmental delay over both time points compared to their Non-FASD counterparts. Demographic and socio-economic factors further impact early childhood. These findings are important in setting up primary level psycho-educational and national prevention programmes especially in periurban communities with a focus on early childhood development and FASD. PMID- 22038429 TI - Prevalence and correlates of psychiatric morbidity among caregivers of children and adolescents with neuropsychiatric disorders in Nigeria. AB - OBJECTIVE: To screen for psychiatric morbidity among caregivers of patients attending a child and adolescent psychiatric clinic. METHOD: A total of 155 patients and their caregivers were consecutively recruited over a 1 month period. Sociodemographic and clinical information on patients was obtained either from the hospital records or from the caregiver. Scoring on the Children's Global Assessment Scale (CGAS) was done by clinicians. The caregivers were administered a sociodemographic questionnaire, GHQ-12, Zarit Burden interview, and the Columbia Impairment Scale. RESULTS: Most caregivers observed in this study were females (80.5%) with mothers of the patients accounting for 78% of all the caregivers. A higher percentage of the patients were males (52.8%). Among the caregivers, 39.4% had GHQ Scores of 3 and above. Factors associated with psychiatric morbidity among caregivers include the high level of subjective burden of care, low level of functioning, high degree of impairment and low level of education among patients. CONCLUSION: The study reveals a high level of psychiatric morbidity among the carers of children and adolescents with mental health problems. PMID- 22038430 TI - The neural correlates of intimate partner violence in women. AB - OBJECTIVE: To examine hippocampal volume and white matter tracts in women with and without intimate partner violence (IPV). METHOD: Nineteen women with IPV exposure in the last year, and 21 women without IPV exposure in the last year underwent structural magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) sequences. Additional data on alcohol use and presence of psychiatric disorder was collected. Differences in fractional anisotropy (FA) between the two groups were examined, using a statistical model that included demographic measures, alcohol use and psychiatric disorder. RESULTS: IPV subjects did not demonstrate significantly different hippocampal volumes compared to subjects without recent IPV. FA was, however, significantly reduced in the body of the corpus callosum of IPV subjects. Adjusting for age, alcohol use, smoking and psychiatric diagnosis did not change the significance of the result. CONCLUSION: Data on hippocampal volume in IPV are inconsistent, perhaps reflecting the fact that multiple factors influence this measure. Reduced FA in the body of the corpus callosum in IPV suggests altered integrity of this white matter tract; additional work is needed to address the underlying mechanisms and clinical correlates of this finding. PMID- 22038431 TI - Dexamethasone induced psychosis presenting with catatonic features. PMID- 22038432 TI - Tracking the legal status of a cohort of inpatients on discharge from a 72-hour assessment unit. PMID- 22038433 TI - Development and characterization of japonica rice lines carrying the brown planthopper-resistance genes BPH12 and BPH6. AB - The brown planthopper (Nilaparvata lugens Stal; BPH) has become a severe constraint on rice production. Identification and pyramiding BPH-resistance genes is an economical and effective solution to increase the resistance level of rice varieties. All the BPH-resistance genes identified to date have been from indica rice or wild species. The BPH12 gene in the indica rice accession B14 is derived from the wild species Oryza latifolia. Using an F(2) population from a cross between the indica cultivar 93-11 and B14, we mapped the BPH12 gene to a 1.9-cM region on chromosome 4, flanked by the markers RM16459 and RM1305. In this population, BPH12 appeared to be partially dominant and explained 73.8% of the phenotypic variance in BPH resistance. A near-isogenic line (NIL) containing the BPH12 locus in the background of the susceptible japonica variety Nipponbare was developed and crossed with a NIL carrying BPH6 to generate a pyramid line (PYL) with both genes. BPH insects showed significant differences in non-preference in comparisons between the lines harboring resistance genes (NILs and PYL) and Nipponbare. BPH growth and development were inhibited and survival rates were lower on the NIL-BPH12 and NIL-BPH6 plants compared to the recurrent parent Nipponbare. PYL-BPH6 + BPH12 exhibited 46.4, 26.8 and 72.1% reductions in population growth rates (PGR) compared to NIL-BPH12, NIL-BPH6 and Nipponbare, respectively. Furthermore, insect survival rates were the lowest on the PYL-BPH6 + BPH12 plants. These results demonstrated that pyramiding different BPH resistance genes resulted in stronger antixenotic and antibiotic effects on the BPH insects. This gene pyramiding strategy should be of great benefit for the breeding of BPH-resistant japonica rice varieties. PMID- 22038434 TI - Fine mapping and analysis of a candidate gene in tomato accession PI128216 conferring hypersensitive resistance to bacterial spot race T3. AB - Bacterial spot caused by Xanthomonas euvesicatoria, X. vesicatoria, X. perforans and X. gardneri is one of the most destructive diseases in tomatoes (Solanum lycopersicum L.) growing in tropical and subtropical regions. Exploring resistance genes from diverse germplasm and incorporating them into cultivated varieties are critical for controlling this disease. The S. pimpinellifolium accession PI128216 was reported to carry the Rx4 gene on chromosome 11 conferring hypersensitivity and field resistance to race T3. To facilitate the use of marker assisted selection in breeding and map-based cloning of the gene, an F(2) population derived from a cross between the susceptible variety OH88119 and the resistant accession PI128216 was created for fine mapping of the Rx4 gene. Using 18 markers developed through various approaches, we mapped the gene to a 45.1-kb region between two markers pcc17 and pcc14 on chromosome 11. A NBS-LRR class of resistance gene was identified as the candidate for the Rx4 gene based on annotation results from the International Tomato Annotation Group. Comparison of the genomic DNA sequences of the Rx4 alleles in PI128216 and OH88119 revealed a 6 bp insertion/deletion (InDel) and eight SNPs. The InDel marker was successfully used to distinguish resistance and susceptibility in 12 tomato lines. These results will facilitate cloning the Rx4 gene and provide a useful tool for marker assisted selection of this gene in tomato breeding programs. PMID- 22038435 TI - Molecular mapping of Rym17, a dominant and rym18 a recessive barley yellow mosaic virus (BaYMV) resistance genes derived from Hordeum vulgare L. AB - PK23-2, a line of six-rowed barley (Hordeum vulgare L.) originating from Pakistan, has resistance to Japanese strains I and III of the barley yellow mosaic virus (BaYMV). To identify the source of resistance in this line, reciprocal crosses were made between the susceptible cultivar Daisen-gold and PK23-2. Genetic analyses in the F(1) generation, F(2) generation, and a doubled haploid population (DH45) derived from the F(1) revealed that PK23-2 harbors one dominant and one recessive resistance genes. A linkage map was constructed using 61 lines of DH45 and 127 DNA markers; this map covered 1268.8 cM in 10 linkage groups. One QTL having a LOD score of 4.07 and explaining 26.8% of the phenotypic variance explained (PVE) for resistance to BaYMV was detected at DNA marker ABG070 on chromosome 3H. Another QTL having a LOD score of 3.53 and PVE of 27.2% was located at marker Bmag0490 on chromosome 4H. The resistance gene on chromosome 3H, here named Rym17, showed dominant inheritance, whereas the gene on chromosome 4H, here named rym18, showed recessive inheritance in F(1) populations derived from crosses between several resistant lines of DH45 and Daisen-gold. The BaYMV recessive resistance genes rym1, rym3, and rym5, found in Japanese barley germplasm, were not allelic to rym18. These results revealed that PK23-2 harbors two previously unidentified resistance genes, Rym17 on 3H and rym18 on 4H; Rym17 is the first dominant BaYMV resistance gene to be identified in primary gene pool. These new genes, particularly dominant Rym17, represent a potentially valuable genetic resource against BaYMV disease. PMID- 22038436 TI - The role of empowerment in youth development: a study of sociopolitical control as mediator of ecological systems' influence on developmental outcomes. AB - Empowerment has become an influential concept and theoretical framework for social policy and practice. Still, relatively little is known about the roles that empowerment plays in the ecology of human development, particularly among young people. This article reports results of a study of psychological empowerment among young people, using data from 629 high school students (65.8% female; 96.5% non-white). Using a path analysis, we examined the role of perceived sociopolitical control--an indicator of the intrapersonal component of psychological empowerment--as a mediator between ecological support systems and developmental outcomes. Findings confirmed that social support in family, peer, and school settings, and family cohesion positively predict self-esteem and perceived school importance, which, in turn, have protective effects on psychological symptoms, violent behaviors and substance use. Sociopolitical control was found to mediate the relationships between ecological supports and risk factors and developmental outcomes, leading to the conclusion that perceived efficacy in the sociopolitical domain, and youth empowerment, more generally, should be considered as core elements of the ecology of human development. Policy and practice aimed at promoting positive developmental outcomes and preventing risk behaviors should take their relationship to sociopolitical control into account. PMID- 22038437 TI - Analysis of ankle-hindfoot stability in patients with ankle instability and normals. AB - PURPOSE: We devised a testing apparatus for in vivo analysis of ankle stability. The purpose of the study was to test the reliability of this apparatus and to determine the stability pattern of the ankle-hindfoot complex in healthy, asymptomatic volunteers and in patients with ankle instability. METHODS: Ten healthy individuals were studied, and testing was repeated on the same day and different days. Three patients with symptomatic, unstable ankles were also tested on both involved and uninvolved sides. Constant inversion torque was applied, then internal rotation torque, while moving the ankle throughout the range of sagittal motion. Three-dimensional kinematics of the ankle-hindfoot complex were measured by an electromagnetic tracking system. RESULTS: Measurements were repeatable, with intraclass correlation coefficients 0.9 or better. Variability was observed among controls, but motion curve patterns were consistent. Motion curve slopes were sensitive in differentiating between unstable and stable ankles. CONCLUSIONS: Most previous reports are in vitro studies conducted with the ankle in one position, manual stress applied, or joint positions estimated with planar radiographs. Our study indicated that more accurate diagnosis of severity of ankle ligament injuries may be possible. PMID- 22038438 TI - Soft tissue balance using the tibia first gap technique with navigation system in cruciate-retaining total knee arthroplasty. AB - PURPOSE: The procedures of bone cut and soft tissue balancing in total knee arthroplasty (TKA) are usually performed using the measured resection technique or the gap technique; however, the superiority of these techniques is controversial. An increase of extension gap after resection of the femoral posterior condyle and a difference between gaps before and after femoral component placement have been reported. We therefore postulated that the use of the tibia first gap technique might have an advantage in avoiding the mismatch before and after resection of the femoral posterior condyle and femoral component placement. METHODS: We performed cruciate-retaining TKAs for 60 varus type osteoarthritic patients with tibia first gap technique using a CT-free navigation system. A TKA tensor designed to facilitate soft tissue balance measurements throughout the range of motion with a reduced and repaired patello-femoral joint was used to assess soft tissue balance (joint gap and varus ligament balance) at extension and flexion between the basic value after tibial cut and the final value following femoral cut and with the femoral component in place. RESULTS: Whereas varus ligament balance at flexion showed significant decrease in the final value at flexion due to the amount of femoral rotation, the basic value of the joint gap before femoral osteotomy reflected the final value following femoral cut and with the femoral component in place. CONCLUSION: The tibia first gap technique may have the advantage that surgeons can predict final soft tissue balance before femoral osteotomies. PMID- 22038439 TI - Revision total hip arthroplasty using a cementless tapered revision stem in patients with a mean age of 82 years. AB - PURPOSE: A tapered straight cementless stem was used for revision in a group of old and very old patients. We wanted to know whether the use of this implant could achieve satisfactory results despite age and osteoporosis. METHODS: We retrospectively analysed data of 77 elderly patients (77 hips) who underwent revision in cemented and uncemented primary total hip arthroplasties (THA). The patients had a mean age of 82.2 years (range, 75-92 years) at revision surgery. They were monitored for a mean follow up of 7.1 years (range, 5.0-10.2 years). During the minimum follow-up period 11 patients died of unrelated causes, leaving 66 patients (66 hips) for evaluation. RESULTS: During the period of study three stems failed due to aseptic loosening, three hips dislocated and were successfully treated by closed reduction and bracing. No infection, osteolysis or significant stress shielding around the stems was observed. The survivorship at an average of 7.1-year follow-up was 95.5%. CONCLUSIONS: These results indicate that this stem is an excellent alternative in revision THA in patients of 75 years or older. PMID- 22038440 TI - Magnetic resonance evaluation of tubercular lesion in spine. AB - PURPOSE: Information on Magnetic Resonance (MR) features of active and healed lesions in tuberculosis (TB) spine are lacking. We evaluated MRI findings in active and healed proven TB spine to establish the diagnostic features. MATERIALS AND METHOD: Forty-nine consecutive spinal TB patients (20 male; 29 female) diagnosed clinicoradiologically and/or on histopathology, Fine Needle Aspiration Cytology (FNAC), bacteriology, or Polymerase Chain Reaction (PCR) were enrolled. Pretreatment MR scans were reviewed for diagnostic features, and eight-month follow-up MR scans were reviewed for healing changes. RESULTS: Cervical spine (n = 6), dorsal spine (n = 14), and lumbar spine (n = 29) were affected. Fourteen had paraplegia. Mean vertebrae involved were 2.61 on X-ray with a total of 128 vertebrae (VB) and 3.2 on MRI (range, 2-15) with 161 VB. The lesions were more extensive on MRI (34.7%) than appreciated on X-ray. The disc was preserved partially or fully in 88.2% of instances. End plate erosions (159/161 VB), lost VB height (94/161), exudative lesion (158/161), granular lesion (3/161), pre and paravertebral collections (49/49 cases), marrow oedema (161/161), discitis (98%), epidural involvement (107/161), epidural spread (100/161), and subligamentous spread (156/161) were observed. Canal encroachment (10-90%) was seen in 37 cases. Mean motor and sensory scores with greater than 50% canal encroachment were 87/100 and 156/168, respectively. Cord oedema was observed in 11 cases (eight with neural deficit and three cases without). Cord atrophy was seen in one case each before and after treatment. A total of 83% of patients had a combination of paravertebral collections, marrow oedema, subligamentous and epidural extension, endplate erosions and discitis. On healing (n = 20), complete resolution of marrow oedema and collections, fatty replacement of bone marrow and resolution of cord signal intensity were observed. CONCLUSION: The marrow oedema, preservation of disc space, subligamentous extension of abscess, septate paravertebral abscess, epidural extension, endplate erosions and discitis were consistently observed in 83% cases of TB spine on MRI. PMID- 22038441 TI - Wide resection of sacral chordoma via a posterior approach. AB - PURPOSE: The study was carried out to report the results of wide resection in sacral chordoma using a posterior approach and gauze packing technique. MATERIALS AND METHODS: The study was carried out between 1990 and 2002; there were 21 patients who underwent the operation. Fourteen patients were male and seven were female. Their ages ranged between 29 and 75 years. Most of the patients presented with sacral mass, pain and neurological deficit. Total sacrectomy and bone reconstruction were carried out in 12 patients. Subtotal sacrectomy was carried out in the remaining nine patients. All patients were followed up for at least seven years. RESULTS: All survived after the operation. Operative time ranged between five and ten hours. All patients needed blood transfusion which ranged between four and 11 units. After the operation, all patients had a certain degree of bowel and bladder dysfunction. Five patients had local complications including infection in three patients with wound disruption and two patients with a seroma. During the follow-up, three patients (14%) had tumour recurrence and one of the patients expired. The remaining 18 patients were still tumour-free at the seven year follow-up. CONCLUSION: Wide resection via the posterior approach and gauze packing technique could be used for management of sacral chordoma with acceptable results. PMID- 22038442 TI - Heat distribution of polymerisation temperature of bone cement on the spinal canal during vertebroplasty. AB - PURPOSE: In the last 15 years, vertebroplasty and kyphoplasty have become established operative procedures for treating osteoporotic vertebral-body fractures and vertebral bodies afflicted with metastases. These procedures are quickly performed with few personnel and material resources and have a low rate of complications. However, cases of neurological impairment are reported in the scientific literature. We analysed whether potentially harmful heat is radiated/conducted by the polymerisation temperature of polymethylmethacrylate (PMMA) bone cement in the spinal canal. METHODS: We performed vertebroplasty on 25 vertebral bodies and measured the temperature distribution during polymerisation of bone cement within the spinal canal using heat probes placed in the respective areas. The vertebral bodies were located in a circulating water bath at 37 degrees C. RESULTS: During polymerisation of the bone cement, a temperature rise was measured. The peak temperature was reached after few minutes. Temperature curves differed; a maximum temperature of up to 43.16 degrees C was detected for a few seconds only. CONCLUSION: When vertebroplasty is performed correctly, there is no temperature development that could eventually damage the spinal cord or spinal nerves. PMID- 22038443 TI - Hip flexor muscle fatigue in patients with symptomatic femoroacetabular impingement. AB - PURPOSE: Patients with symptomatic femoroacetabular impingement (FAI) have considerable hip muscle weakness, in particular, hip flexion and hip adduction. In addition, they experience disabilities while performing prolonged dynamic tasks. It was therefore postulated that, besides hip flexor muscle weakness, patients with symptomatic FAI would show greater hip flexor fatigue compared with healthy controls. METHODS: Hip flexor fatigue was evaluated in two different experiments. Fifteen patients with symptomatic FAI and 15 age-matched healthy controls were tested in each experiment. In the first one, changes in hip flexor torque fluctuations and electromyographic (EMG) activity were measured during a sustained submaximal isometric contraction. In the second experiment, hip flexor torque decline was measured during a series of 20 maximal dynamic contractions. RESULTS: Patients with FAI exhibited hip flexor weakness under both isometric (P = 0.02) and isokinetic conditions (P = 0.03). Fatigue-induced changes in isometric hip flexor torque fluctuations, EMG root mean square and median frequency did not differ significantly between patients and controls (P > 0.05). Similarly, isokinetic hip flexor torque decline was comparable in patients with FAI and controls (P > 0.05). CONCLUSIONS: None of the hip flexor fatigue outcomes considered here differed between patients with symptomatic FAI and controls. Therefore, the disabilities that patients experience while performing prolonged dynamic tasks do not seem to be caused by exaggerated hip flexor muscle fatigue. PMID- 22038444 TI - Lumbar paraspinal compartment syndrome. AB - The purpose of this study was to systematically review the available evidence on lumbar paraspinal compartment syndrome with specific reference to patient demographics, aetiology, types, diagnosis, clinical features, and treatment. This was an Institutional Review Board-exempt study performed at a Level 1 trauma center. A PubMed search was conducted with the title query: lumbar paraspinal compartment syndrome. Eleven articles met our search criteria. Three of the patients with acute paraspinal compartmental syndrome treated with fasciotomy had a full recovery and were able to resume skiing after four months. The aetiology of the onset of lumbar paraspinal compartment syndrome is broadly divided into acute and chronic. Lumbar paraspinal compartment syndrome is one of the causes of back pain with diagnostic clinical features which should be considered in the differential diagnosis of a patient with low back pain. Prospective multicentre trials may provide the surgeon with more insight into the diagnosis and management of lumbar paraspinal compartment syndrome. PMID- 22038445 TI - Percutaneous reduction and leverage fixation using K-wires in paediatric angulated radial neck fractures. AB - PURPOSE: We evaluated the usefulness of percutaneous reduction and leverage fixation using K-wires in children with radial neck fractures. MATERIALS AND METHODS: Between 2006 and 2008, we evaluated 13 paediatric patients with radial neck fractures who had been observed for at least two years and underwent percutaneous reduction and leverage fixation using K-wires. We measured radial angulation and radial translation using preoperative, postoperative and final follow-up radiographs, and we clinically investigated range of motion and carrying angle according to Steele's grading system. RESULTS: Excellent clinical results were achieved in 11 (84.6%) patients, good results in one (7.6%) and fair results in one (7.6%). There were no poor results. The patient in whom fair results were achieved also had an olecranon fracture, which was treated conservatively. Complications such as nonunion, infection, iatrogenic nerve injury and periarticular ossification were minimal. Radioulnar synostosis was absent between the radial neck fracture and the greenstick fracture of the olecranon. Growth arrest in the proximal radial epiphysis was also absent. CONCLUSION: Percutaneous reduction and leverage fixation using K-wires in children with radial neck fractures is a recommended surgical treatment that can achieve recovery of normal radial angulation and elbow motion. PMID- 22038446 TI - The influence of low molecular weight heparin on the expression of osteogenic growth factors in human fracture healing. AB - PURPOSE: Anticoagulant therapy with low molecular weight heparins (LMWH) and mechanical compression is considered the gold standard for the prevention of thrombosis. However, evidence exists that LMWHs impair bone metabolism. The aim of this study was therefore to analyse alterations in the expression of M-CSF, VEGF and TGF-beta1 after treatment with enoxaparin in patients with long bone fracture to investigate the effect of LMWH on human fracture healing. METHODS: A total of 81 patients with long bone fractures were included in the study and divided into two groups. One group comprised patients who received enoxaparin and the other group, patients who did not receive enoxaparin postoperatively. Growth factor levels were analysed in patients' serum and different groups were retrospectively compared. RESULTS: M-CSF serum concentrations were found to be significantly higher only at 48 weeks after surgery in enoxaparin. Mean overall VEGF serum concentration was higher in patients with enoxaparin. TGF-beta1 serum concentrations were higher at 48 weeks after surgery in patients with enoxaparin. CONCLUSION: This is the first comparative systemic measurement of M-CSF, VEGF and TGF-beta1 serum levels in patients with and without enoxaparin after long bone fracture. Significant differences of the expression of the growth factors after enoxaparin therapy were only observed at week 48 after surgery for M-CSF and TGF beta1. PMID- 22038447 TI - The creation of transgenic pigs expressing human proteins using BAC-derived, full length genes and intracytoplasmic sperm injection-mediated gene transfer. AB - In most transgenic (Tg) animals created to date, a transgene consisting of the minimum promoter region linked to a cDNA has been used. However, transgenes on small plasmids are susceptible to the position effect, increasing the difficulty of controlling transgene expression. In this study, we attempted to create Tg pigs by intracytoplasmic sperm injection-mediated gene transfer (ICSI-MGT) using two large genomic transgenes derived from a bacterial artificial chromosome (BAC) containing the full genomic region encoding two human proteins, type I collagen and albumin. The production efficiencies (Tg piglets/live offspring) of type I collagen and albumin Tg pigs were 11.8% (6/51) and 18.2% (2/11), respectively. In all of the Tg pigs examined by real-time PCR analysis, tissue-specific expression of the transgene was confirmed (type I collagen: skin, tendon, vessels, genitalia; albumin: liver). The production of human proteins derived from BAC transgenes was also confirmed. Fluorescence in situ hybridization analysis indicated that the BAC transgenes transferred into porcine oocytes by ICSI-MGT were integrated into single or multiple sites on the host chromosomes. These data demonstrate that Tg pigs expressing human proteins in a tissue-specific manner can be created using a BAC transgenic construct and the ICSI-MGT method. PMID- 22038448 TI - Metabolic syndrome in mice induced by expressing a transcriptional activator in adipose tissue. AB - Metabolic syndrome is a combination of medical disorders that increases the risk of developing cardiovascular disease and diabetes. Constitutive overexpression of 11beta-HSD1 in adipose tissue in mice leads to metabolic syndrome. In the process of generating transgenic mice overexpressing 11beta-HSD1 in an inducible manner, we found a metabolic syndrome phenotype in control, transgenic mice, expressing the reverse tetracycline-transactivator (rtTA) in adipose tissue. The control mice exhibited all four sequelae of metabolic syndrome (visceral obesity, insulin resistance, dyslipidemia, and hypertension), a pro-inflammatory state and marked hepatic steatosis. Gene expression profiling of the adipose tissue, muscle and liver of these mice revealed changes in expression of genes involved in lipid metabolism, insulin resistance, and inflammation. Transient transfection of rtTA, but not tTS, into 3T3-L1 cells resulted in lipid accumulation. We conclude that expression of rtTA in adipose tissue causes metabolic syndrome in mice. PMID- 22038449 TI - Characterization of grape Gibberellin Insensitive1 mutant alleles in transgenic Arabidopsis. AB - We generated 12 different mutations in the grape Gibberellin Insensitive1 (VvGAI1) sequences, transformed them into Arabidopsis under the control of 35S, Arabidopsis GAI or grape GAI1 promoter, and evaluated the impact of these mutant alleles on plant growth and development. These VvGAI1 sequence variants included some mimics of the known GAI-like mutant alleles discovered in grape, wheat, barley, corn, Brassica, and Arabidopsis. In general, plant height and related traits such as length of internodes and inflorescences were significantly reduced for most of the mutant alleles studied, regardless of which promoter was used. Interestingly, the numbers of rosette leaves and lateral branches were generally reduced when a 35S promoter was used to express the mutant alleles, but increased when an Arabidopsis or grape GAI promoter was used. Furthermore, the 35S plants often displayed curly and small leaves. In contrast, the leaves of the plants carrying mutant alleles controlled by a GAI promoter were of variable size, dark green and rarely curly. In addition, when certain VvGAI1 mutant alleles were under the control of the grape GAI1 promoter, the number of pods on inflorescences was significantly increased, but some of the pods produced few seeds due to partial sterility. On the basis of the systematic evaluation of various VvGAI1 mutant alleles in Arabidopsis, we concluded that the VvGAI1 mutant alleles mimicking the GAI or GAI-like mutant variants discovered in wheat, barley and Brassica could potentially be useful for the improvement of grapevine plant architecture. PMID- 22038450 TI - Over-expression of OSRIP18 increases drought and salt tolerance in transgenic rice plants. AB - Both drought and high salinity stresses are major abiotic factors that limit the yield of agricultural crops. Transgenic techniques have been regarded as effective ways to improve crops in their tolerance to these abiotic stresses. Functional characterization of genes is the prerequisite to identify candidates for such improvement. Here, we have investigated the biological functions of an Oryza sativa Ribosome-inactivating protein gene 18 (OSRIP18) by ectopically expressing this gene under the control of CaMV 35S promoter in the rice genome. We have generated 11 independent transgenic rice plants and all of them showed significantly increased tolerance to drought and high salinity stresses. Global gene expression changes by Microarray analysis showed that more than 100 probe sets were detected with up-regulated expression abundance while signals from only three probe sets were down-regulated after over-expression of OSRIP18. Most of them were not regulated by drought or high salinity stresses. Our data suggested that the increased tolerance to these abiotic stresses in transgenic plants might be due to up-regulation of some stress-dependent/independent genes and OSRIP18 may be potentially useful in further improving plant tolerance to various abiotic stresses by over-expression. PMID- 22038451 TI - Pheochromocytomas and paragangliomas: assessment of malignant potential. AB - Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting tumors which arise from the adrenal glands or sympathetic neuronal tissue. Malignant transformation of these tumors occurs in a significant proportion and may therefore lower overall survival rates. In patients with PPGLs it is impossible to identify malignant disease without the presence of metastatic disease, something which can occur as long as 20 years after initial surgery. Early identification of malignant disease would necessitate a more aggressive treatment approach, something which may result in better disease outcome. We have therefore reviewed possible predictors of malignancy and current developments in order to help clinicians to swiftly assess malignant potential in patients with PPGLs. Currently, there is no absolute marker which can objectively reflect malignant potential. Tumor size is the most reliable predictor and should therefore be used as the baseline characteristic. The combination of various clinical markers (extra-adrenal disease and post-operative hypertension), biochemical markers (high dopamine, high norepinephrine and epinephrine to total catecholamine ratio) and/or histological markers (SNAIL, microRNAs and/or microarray results) can raise or lower the suspicion of malignancy. Furthermore, we discuss how clinical markers may affect biochemical results linked to malignancy, how biochemical results may distinguish hereditary syndromes, the role of imaging in determining malignant potential and tumor detection, and recent results of proposed histological markers. PMID- 22038452 TI - Serum AMH concentration as a marker evaluating gonadal function in boys operated on for unilateral cryptorchidism between 1st and 4th year of life. AB - The aim of this study was to measure the serum AMH (anti-Mullerian hormone) concentrations in a group of boys with or without cryptorchidism, evaluation of karyotypes, testicular position, morphology, and major length of the undescended testes. Fifty boys who were 1-4 years old (median = 2.4 years) with unilateral cryptorchidism were evaluated. All of them underwent orchidopexy in 2010. Prior to the procedure, all of the subjects had undergone karyotyping to exclude chromosomal abnormalities. Fifty healthy boys within the same age range (median = 2.1 years) admitted for planned inguinal hernia repair in 2010, served as controls. Blood samples were collected, while obtaining blood for standard laboratory tests routinely performed before the surgeries. Medians of AMH in boys with cryptorchidism were lower than in boys with inguinal hernia and differed significantly between two groups. Undescended testes were generally found in superficial inguinal pouch (n = 46), in two cases were noted to be in the external ring of the inguinal canal, and in another two instances, in the abdominal cavity. The major lengths of the undescended testes were smaller in comparison to the testes positioned normally (mean of 1 cm vs. a mean of 1.5 cm, respectively). In nine of the cases, the testes had turgor deficit, a drop shape, with epididymides that were small, dysplastic, and separated from the testis. The authors found that AMH was lower in boys with unilateral cryptorchidism (also found to have smaller testis) when compared with the control group. PMID- 22038453 TI - The use of combination therapy in the treatment of postmenopausal osteoporosis. AB - In recent years, there has been growing interest in the potential use of combination therapy in the management of osteoporosis in postmenopausal women. Possible regimens include sequential or combined use of anti-resorptive drugs or combinations of anabolic and anti-resorptive agents, given concurrently or in sequence. Combined therapy with anti-resorptive drugs usually produces greater increases in bone mineral density (BMD) than monotherapy but there is no evidence that this results in greater anti-fracture efficacy. The use of bisphosphonates before strontium ranelate or PTH peptides blunts the BMD response. Combined PTH and anti-resorptive therapy results in more rapid gains in spine BMD and a greater increase in hip BMD than PTH monotherapy in the first year of treatment but greater gains in both spine and hip BMD are seen with PTH monotherapy than combined therapy after 2 years of treatment. Anti-resorptive therapy after PTH therapy maintains or increases the gains in BMD. Further research is required to establish the cost-effectiveness and safety of combined and sequential regimens. PMID- 22038454 TI - Filial caregivers; diasporic Chinese compared with homeland and hostland caregivers. AB - This paper examines the distinctiveness and similarities of diasporic Chinese Canadian caregivers to older adults compared with Hong Kong Chinese and Caucasian Canadian caregivers. Particular interest lies in whether filial responsibility, actual caregiving behaviours, health and a variety of structural characteristics cluster in ways that suggest these three groups of filial caregivers are distinctive. Data were collected using face-to-face interviews. The findings suggest that the caregivers participating in this study cluster into types that roughly approximate their original cultural groupings. Interestingly, however, the diasporic or immigrant Chinese appear more similar to homeland (Hong Kong) than hostland (in this instance Caucasian) Canadian caregivers - all diasporic Chinese were originally, or their ancestors were, from Hong Kong. Chinese Canadians are not necessarily in the middle in terms of caregiving behaviours, but rather show variability depending on the behaviour examined. In addition, these findings confirm past research that Western culture does not have clear and explicit norms of filial responsibility to the same extent as does Chinese culture. PMID- 22038455 TI - Culturally and linguistically diverse (CALD) families dealing with dementia: an examination of the experiences and perceptions of multicultural community link workers. AB - Dementia is a chronic illness involving increasing levels of care, often provided by family members, particularly in culturally and linguistically diverse (CALD) communities. Multicultural community link workers are often the primary service providers assisting families to access health and welfare services and as such have extensive experience of, and possess in-depth knowledge about, CALD family care-giving for dementia. While research has been undertaken on dementia in CALD communities, this research has not focused on the experiences and perceptions of these multicultural workers with regards to CALD family care-giving. In response to this gap in the research, this paper presents the results of an empirical investigation of multicultural workers' perspectives with regard to the cultural traditions informing CALD family care-giving, CALD families' understandings of the term 'carer' and family arrangements regarding care. Due to their close relationship and knowledge of families, multicultural workers can offer an important perspective that is invaluable in informing the provision of carer education and support within CALD communities. PMID- 22038456 TI - Gene expression signatures and ex vivo drug sensitivity profiles in children with acute lymphoblastic leukemia. AB - INTRODUCTION: Causes of treatment failure in acute lymphoblastic leukemia (ALL) are still poorly understood. Microarray technology gives new possibilities for the analysis of the biology of leukemias. We hypothesize that drug sensitivity in pediatric ALL is driven by specific molecular mechanisms that correlate with gene expression profiles assessed by microarray analysis. OBJECTIVE: The aim of the study was to determine the ex vivo resistance profiles of 20 antileukemic drugs and gene expression profiles, with relation to response to initial therapy. PATIENTS AND METHODS: Lymphoblasts were analyzed after bone marrow biopsy was obtained from 56 patients. The profile of in vitro resistance to drugs was determined in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) cytotoxicity assay. High-quality total RNA was prepared and hybridized to oligonucleotide arrays HG-U133A 2.0 Chip (Affymetrix). The expression of selected genes was tested by qualitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS AND CONCLUSIONS: The exposure of leukemic blasts to drugs initiates a complex cellular response, which reflects global changes in gene expression. Changes in the expression of several genes are highly correlated with drug resistance. PMID- 22038457 TI - Stathmin expression in glioma-derived microvascular endothelial cells: a novel therapeutic target. AB - The purpose of this study was to investigate stathmin expression and its mechanisms of action in GDMEC. Microvascular endothelial cells were isolated from human gliomas (n=68) and normal brain specimans (n=20), and purified by magnetic beads coated with anti-CD105 antibody. The expression of stathmin mRNA and protein were detected by RT-PCR and western blotting, respectively. Stathmin expression was silenced by application of specific siRNA in high grade GDMEC. The proliferation, apoptosis and invasion behavior of GDMEC were investigated. The stathmin positive rate of endothelial cells in normal brain, grade I-II glioma and grade III-IV glioma was 20, 66 and 95.5%, respectively (P<0.05). When cells were treated with siRNA to silence stathmin, cell viability was reduced, the apoptosis rate increased and the migration of vascular endothelial cells was suppressed significantly (P<0.05). Down-regulation of stathmin suppressed neoangiogenesis of glioma and provides a potential target for glioma treatment. PMID- 22038458 TI - Ab initio and DFT study of luminescent cyclometalated N-heterocyclic carbene organogold(III) complexes. AB - The structures of versatile N-heterocyclic carbene-containing Au(III) complexes in the ground and low-lying excited states have been optimized at the B3LYP functional and the single-excitation configuration interaction (CIS) method, respectively. The spectral properties are predicted with time-dependent density functional theory (TDDFT). In addition, the charge transport quality has been estimated approximately by the predicted reorganization energy (lambda). As revealed from the calculations, the introduction of methyl has a bigger influence on the spectral properties than phenyl. Furthermore, we find that changing the auxiliary ligand could tune the charge transfer properties. PMID- 22038459 TI - Pharmacophore modeling, molecular docking, QSAR, and in silico ADMET studies of gallic acid derivatives for immunomodulatory activity. AB - Immunomodulation refers to an alteration in the immune response due to the intrusion of foreign molecules into the body. In the present communication, QSAR and docking studies of gallic acid derivatives were performed in relation to their immunomodulatory activities. Screening through the use of a QSAR model suggested that the compounds G-4, G-7, G-9, G-10, G-12, and G-13 possess immunomodulatory activity. Activity was predicted using a statistical model developed by the forward stepwise multiple linear regression method. The correlation coefficient (r(2)) and the prediction accuracy (rCV(2)) of the QSAR model were 0.99 and 0.96, respectively. The QSAR study indicated that chemical descriptors-dipole moment, steric energy, amide group count, lambda(max) (UV visible) and molar refractivity-are well correlated with activity, while decreases in the dipole moment, steric energy, and molar refractivity were negatively correlated. A molecular docking study showed that the compounds had high binding affinities for the INFalpha-2, IL-6, and IL-4 receptors. Binding site residues formed H-bonds with the designed gallic acid derivatives G-3, G-4, G-5, G-6, G-7, and G-10. Moreover, based on screening for oral bioavailability, in silico ADME, and toxicity risk assessment, we concluded that compound G-7 exhibits marked immunomodulatory activity, comparable to levamisole. PMID- 22038460 TI - Metastable region of phase diagram: optimum parameter range for processing ultrahigh molecular weight polyethylene blends. AB - Numerous studies suggest that two-phase morphology and thick interface are separately beneficial to the viscosity reduction and mechanical property maintainence of the matrix when normal molecular weight polymer (NMWP) is used for modification of ultrahigh molecular weight polyethylene (UHMWPE). Nevertheless, it is very difficult to obtain a UHMWPE/NMWP blend which may demonstrate both two-phase morphology and thick interface. In this work, dissipative particle dynamics simulations and Flory-Huggins theory are applied in predicting the optimum NMWP and the corresponding conditions, wherein the melt flowability of UHMWPE can be improved while its mechanical properties can also be retained. As is indicated by dissipative particle dynamics simulations and phase diagram calculated from Flory-Huggins theory, too small Flory-Huggins interaction parameter (chi) and molecular chain length of NMWP (N(NMWP)) may lead to the formation of a homogeneous phase, whereas very large interfacial tension and thin interfaces might also appear when parameters N(NMWP) and chi are too large. When these parameters are located in the metastable region of the phase diagram, however, two-phase morphology occurs and interfaces of the blends are extremely thick. Therefore, metastable state is found to be advisable for both the viscosity reduction and mechanical property improvement of the UHMWPE/NMWP blends. PMID- 22038461 TI - The importance of secondary structure in determining CO2-protein binding patterns. AB - One potential means to decrease the level of atmospheric carbon dioxide is through the utilization of protein-CO(2) interactions. A recent bioinformatics analysis [Cundari TR et al. (2009) J Chem Inf Model 49:2111-2115] of these interactions revealed a marked disparity in CO(2) affinity between alpha-helices and beta-sheets. In order to understand this difference, a series of molecular dynamics simulations was performed on polypeptide model systems. Numerous factors that may influence CO(2) affinity were systematically investigated, including the specific location of the amino acids within the secondary structural elements (SSEs), the partial charges on CO(2), chemical modifications made to the protein backbone, the inclusion of singly, doubly, and many functionalized residues, and the effect of solvent water. The differing abilities of the secondary structure types to participate in hydrogen bonding along the backbone were identified as being a crucial influence on CO(2) affinity; the lesser role of polypeptide-CO(2) electrostatic interactions was also noted. The effect of incorporating functionalized amino acid side chains, such as those possessed by Arg and His, on the affinity differs between the two structure types, and also strongly depends on the number included and the distance between them. The inclusion of explicit water molecules was found to attenuate all interactions, but did not change the overall trends in CO(2) affinity. Collectively, these results highlight the role of the backbone atoms in binding the CO(2) ligand, which will have important implications for efforts to ameliorate atmospheric carbon dioxide through the use of natural, designed, and modified proteins. PMID- 22038462 TI - Coffee does not modify postprandial glycaemic and insulinaemic responses induced by carbohydrates. AB - BACKGROUND: Strong epidemiological evidence suggests that coffee consumption is associated with lower risk of type 2 diabetes. In postprandial studies, however, caffeine consumption has been associated with impaired glucose regulation. AIM OF THE STUDY: To study the acute effects of coffee and caffeine-containing soft drinks on glycaemic and insulinaemic responses. DESIGN: Twelve healthy volunteers were served each test food once and the reference glucose solution twice, containing 50 g of available carbohydrates, after an overnight fast at 1-week intervals in a random order. Capillary blood samples were drawn at 15-30 min intervals for 2 h after each study meal. The incremental areas under the curve (IAUC), glycaemic index (GI) and insulinaemic index (II), were calculated to estimate the glycaemic and insulinaemic responses. RESULTS: Glucose and insulin responses of coffees with glucose containing 150 or 300 mg of caffeine did not differ from responses of pure glucose solution; the GIs were 104 and 103, and the IIs were 89 and 92, respectively. When a bun or sucrose and milk were consumed together with coffee, lower GI values and insulin responses were observed, reflecting the carbohydrate quality and protein content of the accompaniments. Sucrose-sweetened cola produced a high GI value of 90 and an II of 61. CONCLUSIONS: Coffee does not modify glycaemic and insulinaemic responses when ingested with a carbohydrate source. Therefore, there is no need to avoid coffee as a choice of beverage in GI testing. PMID- 22038463 TI - Moderate physical training attenuates muscle-specific effects on fibre type composition in adult rats submitted to a perinatal maternal low-protein diet. AB - AIM: To verify whether moderate physical training affects the muscle fibre composition of adult rats subjected to a low protein diet during the perinatal period. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during gestation and lactation: control (17% casein, C) and low protein (8% casein, LP). On postnatal day 60, half of each group was submitted to moderate physical training (8 weeks, 5 days/week(-1), 60 min/day(-1), at 70% of VO(2max), T) or not. After the physical training period, soleus and extensor digitorum longus (EDL) muscles were removed. Myofibrillar ATPase staining was used to classify muscle fibres as type I, IIa, IIb, and intermediate. RESULTS: In the EDL muscle, LP rats showed no changes in the fibre type proportion. Both the C + T and LP + T groups showed a higher percentage of fibres of type IIa, and a lower proportion of fibres of type IIb. In the soleus muscle, LP animals showed a reduction in the proportion of fibre types I and intermediate. C + T rats showed an increase in the fibre type I and IIa. In the LP + T rats, the proportions of the fibre types remained similar to control rats. CONCLUSIONS: Moderate physical training acts as a positive environmental stimulus that reverts the effects of a perinatal low-protein diet on the proportion of fibre types in skeletal muscle. PMID- 22038464 TI - Moderate effects of apple juice consumption on obesity-related markers in obese men: impact of diet-gene interaction on body fat content. AB - PURPOSE: The effect of polyphenol-rich cloudy apple juice (CloA) consumption on plasma parameters related to the obesity phenotype and potential effects of interactions between CloA and allelic variants in obesity candidate genes were assessed in obese men. METHODS: In this controlled, randomized, and parallel study, n = 68, non-smoking, non-diabetic men with a BMI >=27 kg/m(2) received 750 mL/day CloA (802.5 mg polyphenols) or 750 mL/day control beverage (CB, isocaloric equivalent to CloA) for 4 weeks. Further, study participants were genotyped for single-nucleotide polymorphisms in PPARgamma (rs1801282), UCP3 (rs1800849), IL-6 (rs1800795), FABP2 (rs1799883), INSIG2 (rs7566605), and PGC1 (rs8192678) genes. At the beginning and at the end of intervention plasma lipids, distinct adipokines and cytokines as well as anthropometric parameters were determined. RESULTS: CloA compared to CB had no significant effect on plasma lipids, plasma adipokine and cytokine levels, BMI, and waist circumference. However, CloA consumption significantly reduced percent body fat compared to CB (? % body fat: CloA: -1.0 +/- 1.3 vs. CB: -0.2 +/- 0.9, p < 0.05). The IL-6-174 G/C polymorphism showed an interaction with body fat reduction induced by CloA. Solely in C/C, but not in G/C or G/G variants, a significant reduction in body fat after 4 weeks of CloA intervention was detectable. CONCLUSION: The observed diet-gene interaction might be a first indication for the impact of individual genetic background on CloA-mediated bioactivity on obesity-associated comorbidities. PMID- 22038465 TI - Plasma ochratoxin A levels, food consumption, and risk biomarkers of a representative sample of men and women from the Molise region in Italy. AB - BACKGROUND: Ochratoxin A (OTA) is a mycotoxin present in food that can be found in human blood, due to its long half-life. Plasma OTA detection represents a good parameter for evaluating the exposure at the population level. PURPOSE: The relation between plasma OTA levels, dietary habits, and specific disease risk biomarkers (body mass index (BMI), C-reactive protein (CRP), and cardiovascular risk score) was investigated. METHODS: The study involved 327 subjects (150 men and 177 women) aged between 38 and 48 years. Food consumption was evaluated by means of the EPIC questionnaire; plasma OTA was measured by HPLC; CRP was determined in fresh serum samples by a latex particle-enhanced immunoturbidimetric assay. RESULTS: OTA was detected in 99.1% of plasma samples (LOD 25 ng/L); the mean +/- SD value was 0.229 +/- 0.238 ng/mL. However, only 5.2% of samples exceeded 500 ng/L, considered the threshold for a possible pathogenic activity. The estimated mean daily dietary intake of OTA resulted 0.452 +/- 0.468 ng/kg body weight (bw)/day, markedly lower than the tolerable daily intake set by EFSA (17.1 ng/kg bw/day). Processed and mutton/lamb meat were found to contribute most to plasma OTA variance. Nevertheless, cereals, wine, beer, and jam/honey consumption correlated positively with OTA levels. Plasma OTA showed a significant positive association with CRP and cardiovascular risk score (beta = 0.20 +/- 0.08; P = 0.015 and beta = 0.25 +/- 0.08; P = 0.001, respectively); however, the association was present in men but not in women. CONCLUSIONS: Even if the hypothesis of a possible hepatic toxicity of OTA in humans is yet to be verified, the positive association between plasma OTA and CRP may indicate a possible role of OTA in inflammation status and consequently in the genesis of cardiovascular diseases and cancer. PMID- 22038466 TI - Update in geriatric medicine. AB - INTRODUCTION: With an aging population, internists will provide care to a growing number of older adults, a population at risk of developing multiple chronic medical conditions and geriatric syndromes. For this update in geriatric medicine, we highlight recent key articles focused on preventive strategies and lifestyle changes that reduce the burden of disease and functional decline in older adults. METHODS: We identified English-language articles published between March 1, 2010 and March 31, 2011 by review of the contents of major geriatrics/general medicine journals and journal watch services including: New England Journal of Medicine, Annals of Internal Medicine, Journal of the American Medical Association, Lancet, Archives of Internal Medicine, British Medical Journal, Journal of the American Geriatrics Society, and the Journals of Gerontology. We also reviewed updates to the Cochrane database of systematic reviews and articles highlighted by the ACP Journal Club and Journal Watch. Inclusion criteria included (1) randomized controlled trials, (2) conditions exclusive or common to older adults, and (3) commonly seen in generalist practices. After abstract review, each author selected five articles, and these were reviewed again by all authors. Through multiple discussions, consensus was reached on the final articles selected for inclusion based on their quality and potential to improve the health of older patients cared for by generalists. PMID- 22038467 TI - In harm's way. PMID- 22038468 TI - Smoking cessation interventions for patients with depression: a systematic review and meta-analysis. AB - OBJECTIVES: We conducted a systematic literature review of smoking cessation interventions for patients with histories of depressive disorders or current significant depressive symptoms. We examined the comparative effectiveness of smoking cessation strategies on abstinence rates, differential effects of cessation strategies by depression status (i.e., history positive vs. current depression), and differential effects by gender. DATA SOURCES: Peer-reviewed literature in MEDLINE, Embase, PsycINFO, and Cochrane Library. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Randomized controlled trials or secondary analysis of RCT data comparing two or more smoking cessation interventions or intervention to control, and reporting cessation outcomes in adults with depression. STUDY APPRAISAL AND SYNTHESIS METHODS: Two trained researchers screened articles for inclusion. When possible, we estimated pooled risk ratios with 95% confidence intervals by using a random effects model with the Mantel-Haenszel method. We synthesized other studies qualitatively. We classified each intervention as antidepressants, nicotine replacement therapy (NRT), brief smoking cessation counseling, smoking cessation behavioral counseling, or behavioral mood management. RESULTS: We identified 16 unique RCTs, of which, only three trials recruited participants with current depression. Meta analysis demonstrated a small, positive effect of adding behavioral mood management (RR = 1.41, 95% CI 1.01-1.96). All included antidepressant trials showed small, positive effects, but risk ratio summary was not significant (RR = 1.31, 95% CI 0.73-2.34). Three NRT trials demonstrated small, positive effects on smoking cessation rates. We found insufficient evidence to examine gender and depression status moderator effects. LIMITATIONS: Few RCTs exist that test smoking cessation interventions among adults with depression. To make meaningful comparisons, we created broad intervention categories that contained heterogeneity. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Few trials enrolled smokers with current depression. Most of data identified were from subgroup analyses of patients history-positive for depression. However, several promising interventions exist. Healthcare providers should consider encouraging their patients with significant depressive symptoms or depression histories to seek smoking cessation services that include NRT and behavioral mood management. PMID- 22038469 TI - Missed opportunities for advance care planning communication during outpatient clinic visits. AB - BACKGROUND: Early provider-patient communication about future care is critical for patients with heart failure (HF); however, advance care planning (ACP) discussions are often avoided or occur too late to usefully inform care over the course of the disease. OBJECTIVE: To identify opportunities for physicians to engage in ACP discussions and to characterize physicians' responses to these opportunities. DESIGN: Qualitative study of audio-recorded outpatient clinic visits. PARTICIPANTS: Fifty-two patients >= 65 years recently hospitalized for HF with one or more post-discharge follow-up outpatient visits, and their physicians (n = 44), at two Veterans Affairs Medical Centers. APPROACH: Using content analysis methods, we analyzed and coded transcripts of outpatient follow-up visits for 1) patient statements pertaining to their future health or their future physical, psychosocial and spiritual/existential care needs, and 2) subsequent physician responses to patient statements, using an iterative consensus-based coding process. RESULTS: In 13 of 71 consultations, patients expressed concerns, questions, and thoughts regarding their future care that gave providers opportunities to engage in an ACP discussion. The majority of these opportunities (84%) were missed by physicians. Instead, physicians responded by terminating the conversation, hedging their responses, denying the patient's expressed emotion, or inadequately acknowledging the sentiment underlying the patient's statement. CONCLUSIONS: Physicians often missed the opportunity to engage in ACP despite openers patients provided that could have prompted such discussions. Communication training efforts should focus on helping physicians identify patient openers and providing a toolbox to encourage appropriate physician responses; in order to successfully leverage opportunities to engage in ACP discussions. PMID- 22038470 TI - Characterization of MRFAP1 turnover and interactions downstream of the NEDD8 pathway. AB - The NEDD8-Cullin E3 ligase pathway plays an important role in protein homeostasis, in particular the degradation of cell cycle regulators and transcriptional control networks. To characterize NEDD8-cullin target proteins, we performed a quantitative proteomic analysis of cells treated with MLN4924, a small molecule inhibitor of the NEDD8 conjugation pathway. MRFAP1 and its interaction partner, MORF4L1, were among the most up-regulated proteins after NEDD8 inhibition in multiple human cell lines. We show that MRFAP1 has a fast turnover rate in the absence of MLN4924 and is degraded via the ubiquitin proteasome system. The increased abundance of MRFAP1 after MLN4924 treatment results from a decreased rate of degradation. Characterization of the binding partners of both MRFAP1 and MORF4L1 revealed a complex protein-protein interaction network. MRFAP1 bound to a number of E3 ubiquitin ligases, including CUL4B, but not to components of the NuA4 complex, including MRGBP, which bound to MORF4L1. These data indicate that MRFAP1 may regulate the ability of MORF4L1 to interact with chromatin-modifying enzymes by binding to MORF4L1 in a mutually exclusive manner with MRGBP. Analysis of MRFAP1 expression in human tissues by immunostaining with a MRFAP1-specific antibody revealed that it was detectable in only a small number of tissues, in particular testis and brain. Strikingly, analysis of the seminiferous tubules of the testis showed the highest nuclear staining in the spermatogonia and much weaker staining in the spermatocytes and spermatids. MRGBP was inversely correlated with MRFAP1 expression in these cell types, consistent with an exchange of MORF4L1 interaction partners as cells progress through meiosis in the testis. These data highlight an important new arm of the NEDD8-cullin pathway. PMID- 22038471 TI - Additive effect of TAp63 deficiency on the adrenocortical dysplasia (acd) phenotype. AB - Adrenocortical dysplasia (acd) is a spontaneous autosomal recessive mouse mutation exhibiting caudal truncation, vertebral segmentation defects, hydronephrosis, limb hypoplasia, and perinatal lethality. Acd encodes TPP1, a component of the shelterin complex that maintains telomere integrity, and consequently acd mutant mice have telomere dysfunction and genomic instability. We previously showed that apoptosis is the primary mechanism causing the acd skeletal phenotype, and that p53 deficiency rescues the skeletal defects of the acd phenotype but has no effect on the perinatal lethality. The Trp63 gene encodes multiple isoforms, which play a role in proliferation, apoptosis, and stem/progenitor cell maintenance. Different p63 isoforms exhibit both proapoptotic (TAp63) and antiapoptotic (DeltaNp63) functions. We hypothesized that deficiency of proapoptotic TAp63 isoforms might rescue the acd skeletal phenotype, similar to our previous observations with deficiency of p53. Mice heterozygous for a null allele of TAp63 were crossed to heterozygous acd mice to determine the effect of TAp63 deficiency on the acd mutant phenotype. In contrast to our results with the acd * p53 cross, skeletal anomalies were not rescued by deficiency of TAp63. In fact, the limb and vertebral anomalies observed in double mutant embryos were more severe than those of embryos with the acd mutation alone, demonstrating a dose-dependent effect. These studies suggest that TAp63 isoforms do not facilitate p53-like apoptosis during development in response to acd-mediated telomere dysfunction and are consistent with the proposed roles of TAp63 in maintaining genomic stability. PMID- 22038472 TI - Anxiety and perceptual-motor performance: toward an integrated model of concepts, mechanisms, and processes. AB - Under anxiety, people sometimes perform poorly. This concerns cognitive performance (e.g., taking an important exam) as well as perceptual-motor performance (e.g., picking up a cup from a table). There is still much debate about how anxiety affects perceptual-motor performance. In the current paper we review the experimental literature on anxiety and perceptual-motor performance, thereby focusing on how anxiety affects the perception, selection, and realization of action possibilities. Based on this review we discuss the merits of two opposing theoretical explanations and build on existing frameworks of anxiety and cognitive performance to develop an integrated model that explains the various ways in which anxiety may specifically affect perceptual-motor performance. This model distinguishes between positive and negative effects of anxiety and, moving beyond previous approaches, recognizes three operational levels (i.e., attentional, interpretational, and behavioral) at which anxiety may affect different aspects of goal-directed action. Finally, predictions are formulated and directions for future research suggested. PMID- 22038473 TI - Physicochemical characterization and water vapor sorption of organic solution advanced spray-dried inhalable trehalose microparticles and nanoparticles for targeted dry powder pulmonary inhalation delivery. AB - Novel advanced spray-dried inhalable trehalose microparticulate/nanoparticulate powders with low water content were successfully produced by organic solution advanced spray drying from dilute solution under various spray-drying conditions. Laser diffraction was used to determine the volumetric particle size and size distribution. Particle morphology and surface morphology was imaged and examined by scanning electron microscopy. Hot-stage microscopy was used to visualize the presence/absence of birefringency before and following particle engineering design pharmaceutical processing, as well as phase transition behavior upon heating. Water content in the solid state was quantified by Karl Fisher (KF) coulometric titration. Solid-state phase transitions and degree of molecular order were examined by differential scanning calorimetry (DSC) and powder X-ray diffraction, respectively. Scanning electron microscopy showed a correlation between particle morphology, surface morphology, and spray drying pump rate. All advanced spray-dried microparticulate/nanoparticulate trehalose powders were in the respirable size range and exhibited a unimodal distribution. All spray-dried powders had very low water content, as quantified by KF. The absence of crystallinity in spray-dried particles was reflected in the powder X-ray diffractograms and confirmed by thermal analysis. DSC thermal analysis indicated that the novel advanced spray-dried inhalable trehalose microparticles and nanoparticles exhibited a clear glass transition (T(g)). This is consistent with the formation of the amorphous glassy state. Spray-dried amorphous glassy trehalose inhalable microparticles and nanoparticles exhibited vapor-induced (lyotropic) phase transitions with varying levels of relative humidity as measured by gravimetric vapor sorption at 25 degrees C and 37 degrees C. PMID- 22038474 TI - Once daily, high-dose mesalazine controlled-release tablet for colonic delivery: optimization of formulation variables using Box-Behnken design. AB - The aim of this work was to statistically optimize a novel high-dose, mesalazine colonic delivery matrix system, potentially suitable for once daily administration, using simple wet granulation method. A hydrophobic-hydrophilic polymeric blend was used to manipulate drug release. A three-factor, three-level Box-Behnken design was used to construct polynomial models correlating the dependent and independent variables. Independent formulation variables were the percentages of the hydrophilic polymer Carbopol(r) 940, hydrophobic polymer Eudragit(r) RS, and the superdisintegrant croscarmellose sodium. The cumulative percentages of drug released at 6, 10, and 14 h were selected as dependent variables and restricted to 7.5-22.5% (Y(1)), 42.5-57.5 % (Y(2)), and 72.5-87.5% (Y(3)), respectively. A second-order polynomial equation fitted to the data was used to optimize the independent formulation variables. Based on Box-Behnken experimental design, different mesalazine release profiles were obtained. The optimized formulation containing 5.72% Carbopol(r), 9.77% Eudragit(r) RS, and 1.45% croscarmellose sodium was prepared according to the software determined levels. It provided a release profile which was very close to the targeted release profile, where the calculated values of f(1) and f(2) were 8.47 and 67.70, respectively, and followed zero-order release kinetics. PMID- 22038475 TI - Development, optimization, and anti-diabetic activity of gliclazide-loaded alginate-methyl cellulose mucoadhesive microcapsules. AB - The purpose of this work was to develop and optimize gliclazide-loaded alginate methyl cellulose mucoadhesive microcapsules by ionotropic gelation using central composite design. The effect of formulation parameters like polymer blend ratio and cross-linker (CaCl(2)) concentration on properties of gliclazide-loaded alginate-methyl cellulose microcapsules like drug encapsulation efficiency and drug release were optimized. The optimized microcapsules were subjected to swelling, mucoadhesive, and in vivo studies. The observed responses coincided well with the predicted values from the optimization technique. The optimized microcapsules showed high drug encapsulation efficiency (83.57 +/- 2.59% to 85.52 +/- 3.07%) with low T(50%) (time for 50% drug release, 5.68 +/- 0.09 to 5.83 +/- 0.11 h). The in vitro drug release pattern from optimized microcapsules was found to be controlled-release pattern (zero order) with case II transport release mechanism. Particle sizes of these optimized microcapsules were 0.767 +/- 0.085 to 0.937 +/- 0.086 mm. These microcapsules also exhibited good mucoadhesive properties. The in vivo studies on alloxan-induced diabetic rats indicated the significant hypoglycemic effect that was observed 12 h after oral administration of optimized mucoadhesive microcapsules. The developed and optimized alginate methyl cellulose microcapsules are suitable for prolonged systemic absorption of gliclazide to maintain lower blood glucose level and improved patient compliance. PMID- 22038476 TI - Investigation of PLLA/PCL blends and paclitaxel release profiles. AB - Blends of poly (L-lactide) (PLLA) and poly (epsilon-caprolactone) (PCL) with and without paclitaxel were prepared via solution casting. DSC analysis as well as SEM analysis of the PLLA/PCL blend solution cast films showed that these blends are all phase separated.%PLLA crystallinity was found to increase with increasing PCL content (up till 15 wt.%). The PCL phase is found to homogeneously disperse in the PLLA matrix as spherical domains where the pore diameters of the PCL domains significantly increased with increasing PCL content. The degradation profiles matched with the slower degrading component PCL rather than PLLA and also increasing PCL content of the blends increased the degradation rate relatively. The increased crystallinity of the PLLA phase with increasing PCL contents confirmed that the degradation occurred through PCL phase. Cell proliferation on PLLA/PCL blends showed that all these blends were suitable for the support of cellular growth. Apoptosis assay with the paclitaxel-loaded PLLA/PCL blends showed an increase in cell death throughout 7 days of incubation where the cell death was increased with increasing PCL contents. This was attributed to the faster release of paclitaxel which was at least partially affected by the faster degradation rate at increasing PCL contents. The paclitaxel release was shown to be degradation controlled in the initial stages followed by a faster diffusion-controlled release in the later stages. These polymer blends were found to be very suitable paclitaxel release agents for which the paclitaxel release times can be altered with the composition of the blend and the film thickness. PMID- 22038477 TI - Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice. AB - Liver cirrhosis is characterized by an excessive accumulation of extracellular matrix components, including hyaluronan (HA). In addition, cirrhosis is considered a pre-neoplastic disease for hepatocellular carcinoma (HCC). Altered HA biosynthesis is associated with cancer progression but its role in HCC is unknown. 4-Methylumbelliferone (4-MU), an orally available agent, is an HA synthesis inhibitor with anticancer properties. In this work, we used an orthotopic Hepa129 HCC model established in fibrotic livers induced by thioacetamide. We evaluated 4-MU effects on HCC cells and hepatic stellate cells (HSCs) in vitro by proliferation, apoptosis and cytotoxicity assays; tumor growth and fibrogenesis were also analyzed in vivo. Our results showed that treatment of HCC cells with 4-MU significantly reduced tumor cell proliferation and induced apoptosis, while primary cultured hepatocytes remained unaffected. 4-MU therapy reduced hepatic and systemic levels of HA. Tumors systemically treated with 4-MU showed the extensive areas of necrosis, inflammatory infiltrate and 2-3-fold reduced number of tumor satellites. No signs of toxicity were observed after 4-MU therapy. Animals treated with 4-MU developed a reduced fibrosis degree compared with controls (F1-2 vs F2-3, respectively). Importantly, 4-MU induced the apoptosis of HSCs in vitro and decreased the amount of activated HSCs in vivo. In conclusion, our results suggest a role for 4-MU as an anticancer agent for HCC associated with advanced fibrosis. PMID- 22038478 TI - Differential expression of disialic acids in the cerebellum of senile mice. AB - It is known that disialic acids (diSia) are present in the mammalian brain. However, the precise anatomical distribution and the chronology of its expression along life are not well studied yet. It is accepted that the transfer of diSia in the brain is mediated mainly by the enzyme ST8Sia III (alpha2,8-sialyltransferase III). We studied the expression of diSia glycoepitopes and of the ST8Sia III gene in different structures of the mouse brain at different postnatal stages by immunohistochemistry and real-time polymerase chain reaction, respectively. C57BL/6 mice of different stages were used. Samples of hippocampus, olfactory bulb, cortex and cerebellum were processed for studies of molecular biology and immunohistochemistry. Histological analysis revealed an important decrease in diSia labeling in the senile cerebellum compared with other structures and stages (P ? 0.001). In concordance with these results, a significant decrease in ST8Sia III gene expression was found in the cerebellum of senile animals (P < 0.001). These results suggest that diSia are constantly expressed but with differential expression in various areas of the mouse central nervous system. On the other hand, the concordance in the decreased expression of ST8Sia III and the diSia epitope in the cerebellum of senile animals suggest a role of diSia in this structure or, inversely, an influence of aging on the expression of diSia in the cerebellum. Further research in that direction could elucidate the roles of diSia in brain function in health and disease. PMID- 22038479 TI - Isomeric analysis of oligomannosidic N-glycans and their dolichol-linked precursors. AB - Oligomannosidic (OM) N-glycans occur as a mixture of isomers, which at early stages of glycosidase trimming also comprise structures with one to three glucose residues. A complementary set of isomers is generated during the biosynthesis of the lipid-linked precursor. Here, we demonstrate the remarkable capacity of liquid chromatography (LC) with porous graphitic carbon and mass spectrometric detection for the determination of OM isomers. Protein-linked N-glycans were released enzymatically from samples with known isomer composition such as kidney bean proteins and ribonuclease B. Lipid-linked oligosaccharides were obtained by a direct mild acid hydrolysis of microsomes thus avoiding biphasic partitioning. A parallel analysis of pyridylaminated glycans by amide-silica and reversed-phase high-performance LC, the application of branch-specific alpha-mannosidases and work with ALG mutant plants led to the assignment of the relative retention times of the isomers occurring during the degradation of the Glc(3)Man(9)GlcNAc(2) precursor oligosaccharide to Man(5)GlcNAc(2) and beyond. A tightly woven net of evidence supports these assignments. Noteworthy, this isomer assignment happens in the course of a comprehensive analysis of all types of a sample's N-glycans. PMID- 22038480 TI - Evaluation of immunostimulatory effect of the arrowroot (Maranta arundinacea. L) in vitro and in vivo. AB - Arrowroot (Maranta arundinacea. L) is an underutilized local crop potentially to be developed as carbohydrate source and functional food in Indonesia. The objectives of this research are to evaluate the immunostimulatory effects of arrowroot extracts in vitro by using animal cell culture techniques, and in vivo by using BALB/c mice. The arrowroot tuber extracts were prepared by heat treatment at 121 degrees C for 20 min in distilled water. The IgM production stimulatory activity of arrowroot tuber extracts against human hybridoma HB4C5 cells and mouse splenocytes was assessed. The result indicated that the arrowroot tuber extract stimulated IgM production by HB4C5 cells and immunoglobulin (IgG, IgA and IgM) production by splenocytes in vitro. In addition, the arrowroot tuber extracts strongly enhanced interferon gamma production by splenocytes. In vivo study indicated that the diet containing arrowroot extracts increased the serum IgG, IgA and IgM levels in mice. These results revealed that the arrowroot tuber extracts have immunostimulatory effects in vivo as well as in vitro. PMID- 22038481 TI - Unmet needs and distress in people with inoperable lung cancer at the commencement of treatment. AB - PURPOSE: People with lung cancer report a higher burden of unmet needs, specifically psychological and daily living unmet needs. They experience more psychological distress and more physical hardship than other tumour sites. This study examined the levels of unmet need and psychological distress in inoperable lung cancer patients at the start of treatment. METHODS: A cross-section survey methodology was employed using baseline data from a randomised controlled trial designed to evaluate a supportive care intervention. Eligible lung cancer patients were approached to participate at the start of treatment. Consenting patients completed questionnaires prior to or just after the commencement of treatment. Reliable and valid measures included Needs Assessment for Advanced Lung Cancer Patients, Hospital Anxiety and Depression Scale and Brief Distress Thermometer. RESULTS: Of the 108 patients participating, the top unmet need was 'Dealing with concerns about your family's fears and worries' (62%); with the next four also coming from the psychological/emotional domain, but, on average, most needs related to medical communication. Thirty two percent of patients reported clinical or subclinical anxiety and 19% reported HADS scores suggestive of clinical or subclinical depression. Moreover, 39.8% of the sample reported distress above the cut-off on the distress thermometer and this was associated with higher needs for each need subscale (p < 0.05). CONCLUSIONS: People with lung cancer have high levels of unmet needs especially regarding psychological/emotional or medical communication. People with lung cancer who are classified as distressed have more unmet needs. PMID- 22038482 TI - Psychometric validation and reliability analysis of a Spanish version of the patient satisfaction with cancer-related care measure: a patient navigation research program study. AB - BACKGROUND: Patient satisfaction (PS), a key measure of quality of cancer care, is a core study outcome of the multi-site National Cancer Institute-funded Patient Navigation Research Program. Despite large numbers of underserved monolingual Spanish speakers (MSS) residing in USA, there is no validated Spanish measure of PS that spans the whole spectrum of cancer-related care. The present study reports on the validation of the Patient Satisfaction with Cancer Care (PSCC) measure for Spanish (PSCC-Sp) speakers receiving diagnostic and therapeutic cancer-related care. METHODS: Original PSCC items were professionally translated and back translated to ensure cultural appropriateness, meaningfulness, and equivalence. Then, the resulting 18-item PSCC-Sp measure was administered to 285 MSS. We evaluated latent structure and internal consistency of the PSCC-Sp using principal components analysis (PCA) and Cronbach coefficient alpha (alpha). We used correlation analyses to demonstrate divergence and convergence of the PSCC-Sp with a Spanish version of the Patient Satisfaction with Interpersonal Relationship with Navigator (PSN-I-Sp) measure and patients' demographics. RESULTS: The PCA revealed a coherent set of items that explicates 47% of the variance in PS. Reliability assessment demonstrated that the PSCC-Sp had high internal consistency (alpha = 0.92). The PSCC-Sp demonstrated good face validity and convergent and divergent validities as indicated by moderate correlations with the PSN-I-Sp (p = 0.003) and nonsignificant correlations with marital status and household income (all p(s) > 0.05). CONCLUSION: The PSCC-Sp is a valid and reliable measure of PS and should be tested in other MSS populations. PMID- 22038483 TI - Ahnak1 is a tuneable modulator of cardiac Ca(v)1.2 calcium channel activity. AB - Ahnak1 has been implicated in the beta-adrenergic regulation of the cardiac L type Ca(2+) channel current (I (CaL)) by its binding to the regulatory Cavbeta(2) subunit. In this study, we addressed the question whether ahnak1/Cavbeta(2) interactions are essential or redundant for beta-adrenergic stimulation of I (CaL). Three naturally occurring ahnak1 variants (V5075 M, G5242R, and T5796 M) identified by genetic screening of cardiomyopathy patients did essentially not influence the in vitro Cavbeta(2) interaction as assessed by recombinant proteins. But, we observed a robust increase in Cavbeta(2) binding by mutating Ala at position 4984 to Pro which creates a PxxP consensus motif in the ahnak1 protein fragment. Surface plasmon resonance measurements revealed that this mutation introduced an additional Cavbeta(2) binding site. The functionality of A4984P was supported by the specific action of the Pro-containing ahnak1-derived peptide (P4984) in beta-adrenergic regulation of I (CaL). Patch clamp recordings on cardiomyocytes showed that intracellular perfusion of P4984 markedly reduced I (CaL) response to the beta-adrenergic agonist, isoprenaline, while the Ala containing counterpart failed to affect I (CaL). Interestingly, I (CaL) of ahnak1 deficient cardiomyocytes was not affected by peptide application. Moreover, I (CaL) of ahnak1-deficient cardiomyocytes showed intact beta-adrenergic responsiveness. Similarly isolated ahnak1-deficient mouse hearts responded normally to adrenergic challenge. Our results indicate that ahnak1 is not essential for beta-adrenergic up-regulation of I (CaL) and cardiac contractility in mice. But, tuning ahnak1/Cavbeta(2) interaction provides a tool for modulating the beta-adrenergic response of I (CaL). PMID- 22038484 TI - Obesity and blood pressure levels of adolescents in Abeokuta, Nigeria. AB - BACKGROUND: We determined the prevalence of general and central obesity and their relationship with blood pressure levels among adolescents in Abeokuta, Nigeria. METHODS: We selected 423 adolescents from seven schools in Abeokuta, Nigeria, using a multistage random-sampling technique. Body mass index (BMI), waist circumference (WC) and blood pressures were measured. RESULTS: Twenty-one (5%) children had general obesity and 109 (24.5%) had central obesity. Of those with general obesity, 20 (95.1%) children were centrally obese. With simple linear regression analysis, BMI and WC explained 10.7 and 8.4%, respectively of the variance in systolic blood pressure (SBP), and 3.6 and 2.7%, respectively of the variance in diastolic blood pressure (DBP). Following logistic regression analysis, BMI was the major factor determining SBP levels (OR 0.8, 95% CI: 0.65 0.99, p < 0.05). CONCLUSION: BMI remains an important anthropometric screening tool for high blood pressure in Nigerian adolescents. PMID- 22038485 TI - A new broccoli * broccoli immortal mapping population and framework genetic map: tools for breeders and complex trait analysis. AB - A unique broccoli * broccoli doubled haploid (DH) population has been created from the F(1) of a cross between two DH broccoli lines derived from cultivars Green Duke and Marathon. We genotyped 154 individuals from this population with simple sequence repeat and amplified fragment length polymorphism markers to create a B. oleracea L. var. italica 'intra-crop' specific framework linkage map. The map is composed of nine linkage groups with a total length of 946.7 cM. Previous published B. oleracea maps have been constructed using diverse crosses between morphotypes of B. oleracea; this map therefore represents a useful breeding resource for the dissection of broccoli specific traits. Phenotype data have been collected from the population over five growing seasons; the framework linkage map has been used to locate quantitative trait loci for agronomically important broccoli traits including head weight (saleable yield), head diameter, stalk diameter, weight loss and relative weight loss during storage, as well as traits for broccoli leaf architecture. This population and associated linkage map will aid breeders to directly map agronomically important traits for the improvement of elite broccoli cultivars. PMID- 22038486 TI - Genetic mapping of the Leptosphaeria maculans avirulence gene corresponding to the LepR1 resistance gene of Brassica napus. AB - AvrLepR1 of the fungal pathogen Leptosphaeria maculans is the avirulence gene that corresponds to Brassica LepR1, a plant gene controlling dominant, race specific resistance to this pathogen. An in vitro cross between the virulent L. maculans isolate, 87-41, and the avirulent isolate, 99-56, was performed in order to map the AvrLepR1 gene. The disease reactions of the 94 of the resulting F(1) progenies were tested on the canola line ddm-12-6s-1, which carries LepR1. There were 44 avirulent progenies and 50 virulent progenies suggesting a 1:1 segregation ratio and that the avirulence of 99-56 on ddm-12-6s-1 is controlled by a single gene. Tetrad analysis also indicated a 1:1 segregation ratio. The AvrLepR1 gene was positioned on a genetic map of L. maculans relative to 259 sequence-related amplified polymorphism (SRAP) markers, two cloned avirulence genes (AvrLm1 and AvrLm4-7) and the mating type locus (MAT1). The genetic map consisted of 36 linkage groups, ranging in size from 13.1 to 163.7 cM, and spanned a total of 2,076.4 cM. The AvrLepR1 locus was mapped to linkage group 4, in the 13.1 cM interval flanked by the SRAP markers SBG49-110 and FT161-223. The AvrLm4-7 locus was also positioned on linkage group 4, close to but distinct from the AvrLepR1 locus, in the 5.4 cM interval flanked by FT161-223 and P1314-300. This work will make possible the further characterization and map-based cloning of AvrLepR1. A combination of genetic mapping and pathogenicity tests demonstrated that AvrLepR1 is different from each of the L. maculans avirulence genes that have been characterized previously. PMID- 22038487 TI - Fine genetic mapping of greenbug aphid-resistance gene Gb3 in Aegilops tauschii. AB - The greenbug, Schizaphis graminum (Rondani), is an important aphid pest of small grain crops especially wheat (Triticum aestivum L., 2n = 6x = 42, genomes AABBDD) in many parts of the world. The greenbug-resistance gene Gb3 originated from Aegilops tauschii Coss. (2n = 2x = 14, genome D(t)D(t)) has shown consistent and durable resistance against prevailing greenbug biotypes in wheat fields. We previously mapped Gb3 in a recombination-rich, telomeric bin of wheat chromosome arm 7DL. In this study, high-resolution genetic mapping was carried out using an F(2:3) segregating population derived from two Ae. tauschii accessions, the resistant PI 268210 (original donor of Gb3 in the hexaploid wheat germplasm line 'Largo') and susceptible AL8/78. Molecular markers were developed by exploring bin-mapped wheat RFLPs, SSRs, ESTs and the Ae. tauschii physical map (BAC contigs). Wheat EST and Ae. tauschii BAC end sequences located in the deletion bin 7DL3-0.82-1.00 were used to design STS (sequence tagged site) or CAPS (Cleaved Amplified Polymorphic Sequence) markers. Forty-five PCR-based markers were developed and mapped to the chromosomal region spanning the Gb3 locus. The greenbug-resistance gene Gb3 now was delimited in an interval of 1.1 cM by two molecular markers (HI067J6-R and HI009B3-R). This localized high-resolution genetic map with markers closely linked to Gb3 lays a solid foundation for map based cloning of Gb3 and marker-assisted selection of this gene in wheat breeding. PMID- 22038489 TI - Single-stage posterior instrumentation and anterior debridement for active tuberculosis of the thoracic and lumbar spine with kyphotic deformity. AB - OBJECTIVE: The purpose of this study was to validate the efficacy and safety of single-stage posterior instrumentation and anterior debridement for treatment of active spinal tuberculosis with kyphotic deformity. METHOD: From January 2005 to January 2009, 13 males and 24 females were enrolled in this retrospective study. All patients underwent single-stage posterior instrumentation and fusion, combined with anterior radical debridement and bone grafting. Clinical and radiographic results were analysed. RESULTS: Patients were followed-up for 33.6 months on average. Bony fusion was achieved at six- to nine-month follow-up in all patients. The respective average kyphosis at the pre-operative and the last follow-up was 53.5 degrees and 12.6 degrees , with a mean correction of 40.9 degrees (78.5%). Neurologic recovery averaged 1.5 grades on the Frankel scale. No recurrence of tuberculosis or instrumentation failure occurred. CONCLUSION: Single-stage posterior instrumentation and anterior debridement with fusion was demonstrated to be a safe and effective method to achieve spinal decompression and kyphosis correction in patients with Pott's disease. PMID- 22038488 TI - Development and characterization of genomic and expressed SSRs for levant cotton (Gossypium herbaceum L.). AB - Four microsatellite-enriched genomic libraries for CA(15), GA(15), AAG(8) and ATG(8) repeats and transcriptome sequences of five cDNA libraries of Gossypium herbaceum were explored to develop simple sequence repeat (SSR) markers. A total of 428 unique clones from repeat enriched genomic libraries were mined for 584 genomic SSRs (gSSRs). In addition, 99,780 unigenes from transcriptome sequencing were explored for 8,900 SSR containing sequences with 12,471 expressed SSRs. The present study adds 1,970 expressed SSRs and 263 gSSRs to the public domain for the use of genetic studies of cotton. When 150 gSSRs and 50 expressed SSRs were tested on a panel of four species of cotton, 68 gSSRs and 12 expressed SSRs revealed polymorphism. These 200 SSRs were further deployed on 15 genotypes of levant cotton for the genetic diversity assessment. This is the first report on the successful use of repeat enriched genomic library and expressed sequence database for microsatellite markers development in G. herbaceum. PMID- 22038490 TI - Two types of partial fertility in a diploid population of the fern Thelypteris decursive-pinnata (Thelypteridaceae). AB - Two types of abnormal sporophytes were observed in a population of diploid Thelypteris decursive-pinnata. Most sporophytes in this population exhibited regular chromosome pairing, resulting in the formation of 30 bivalents in meiosis I; however, they produced abortive spores to various degrees. Some formed large globose spores at low frequencies, most likely to be unreduced diplospores. The other type of abnormal sporophyte underwent synaptic failure to form 60 univalents at meiosis I, but produced fertile spores, mostly large globose ones at low frequencies. The globose spores were considered unreduced diplospores because the gametophytes arising from them produced tetraploid sporophytes by gametophytic selfing. One tetraploid formed only univalents at meiosis I. Allozyme variation was not detected in this population, although neighboring ordinary diploid populations exhibited it to a certain degree. The sympatric occurrence and allozyme uniformity of the two groups suggest that both are offspring of a founder sporophyte, which may have possessed two types of mutated recessive genes responsible for the spore sterility and the synaptic failure in meiosis. Unreduced spores formed by these two types may play an important role in the polyploid speciation of this species. PMID- 22038491 TI - Lamb survival analysis from birth to weaning in Iranian Kermani sheep. AB - Survival records from 1,763 Kermani lambs born between 1996 and 2004 from 294 ewes and 81 rams were used to determine genetic and non-genetic factors affecting lamb survival. Traits included were lamb survival across five periods from birth to 7, 14, 56, 70, and 90 days of age. Traits were analyzed under Weibull proportional hazard sire models. Several binary analyses were also conducted using animal models. Statistical models included the fixed class effects of sex of lamb, month and year of birth, a covariate effect of birth weight, and random genetic effects of both sire (in survival analyses) and animal (in binary analyses). The average survival to 90 days of age was 94.8%. Hazard rates ranged from 1.00 (birth to 90 days of age) to 1.73 (birth to 7 days of age) between the two sexes indicating that male lambs were at higher risk of mortality than females (P < 0.01). This study also revealed a curvilinear relationship between lamb survival and lamb birth weight, suggesting that viability and birth weight could be considered simultaneously in the selection programs to obtain optimal birth weight in Kermani lambs. Estimates of heritabilities from survival analyses were medium and ranged from 0.23 to 0.29. In addition, heritability estimates obtained from binary analyses were low and varied from 0.04 to 0.09. The results of this study suggest that progress in survival traits could be possible through managerial strategies and genetic selection. PMID- 22038492 TI - Assessment of long-term efficacy and safety of metyrapone monotherapy in a patient with ACTH-independent macronodular adrenal hyperplasia. PMID- 22038494 TI - Retraction note: Isolation and characterization of goat retinal microvascular endothelial cells. PMID- 22038493 TI - High tie in anterior resection for rectal cancer confers no increased risk of anastomotic leakage. AB - BACKGROUND: It is controversial whether division of the inferior mesenteric artery close to the aorta influences the risk of anastomotic leakage, especially in the elderly and unfit. This population-based study was carried out to evaluate the independent association between a high arterial ligation and anastomotic leakage in anterior resection for rectal cancer. METHODS: All patients who had anterior resection for rectal cancer from 2007 to 2009 inclusive were identified in the Swedish Colorectal Cancer Registry. The association between high tie and anastomotic leakage was evaluated in a logistic regression model, with adjustment for confounders. Stratification was performed for co-morbidity as judged by the American Society of Anesthesiologists (ASA) classification. RESULTS: Symptomatic anastomotic leakage occurred in 81 (9.9 per cent) of 818 patients with a high tie and 108 (9.8 per cent) of 1101 without. Overall, the use of a high tie was not associated with a higher risk of anastomotic leakage (odds ratio (OR) 1.00, 95 per cent confidence interval 0.72 to 1.39). There was no increased risk in patients classifed as ASA grade I or II (OR 0.97, 0.69 to 1.35), or in those graded ASA III or IV (OR 1.26, 0.58 to 2.75). CONCLUSION: In the present population-based setting, use of a high tie was not associated with an increased rate of symptomatic anastomotic leakage. PMID- 22038495 TI - Acute myocardial infarction in streptozotocin-induced hyperglycaemic rats: protection by a carbon monoxide-releasing molecule (CORM-3). AB - Here, we have studied the effects of a carbon monoxide-releasing molecule (CORM 3, tricarbonylchloro(glycinato)ruthenium(II)) on acute myocardial ischemia/reperfusion (I/R) injury in hyperglycaemic streptozotocin-treated rats (STZ rats). Occlusion of the left descending coronary artery for 25 min followed by a 2-h reperfusion in STZ-induced hyperglycaemic rats was used as the model. CORM-3 and its inactive counterpart (iCORM-3) were administered 1 h prior to ischemia. The parameters measured included myocardial infarct size (IS) and a selection of inflammatory, oxidative markers and endothelial progenitor cells (CD34+ and CD117/c-kit+. In STZ-induced hyperglycaemic rats, occlusion of the left descending coronary artery caused injury of the myocardial tissue with an IS of ~70%, expressed as fraction of the area at risk. Given intraperitoneally 1 h prior to ischemia, CORM-3 (2-8 mg/kg) afforded significant dose-dependent cardio protection. Specifically, pre-treatment with CORM-3 reduced infarct size by 14 +/ 0.6%, 34 +/- 1% and 53 +/- 1.6% for doses of 2, 4 and 8 mg/kg, respectively. A negative control (iCORM-3) failed to prevent the cardiac damage induced by I/R. CORM-3 pre-treatment augmented cardiac heme oxygenase-1 (HO-1) protein levels and was associated with an increased number of CD34+- and CD117/c-kit+-positive immunostaining. Modulation of these markers was associated with augmented cardiac eNOS expression and levels of the cytokines TNF-alpha and IL-1 beta. CORM-3 afforded significant cardio-protection against acute myocardial infarction in STZ induced hyperglycaemic rats through liberation of small amounts of CO. Of interest, CORM-3 promoted recruitment of the endogenous endothelial progenitor cells within the myocardium, possibly through modulation of cardiac HO-1 and eNOS expression and/or function. PMID- 22038496 TI - Flow visualization for different port angles of a pulsatile ventricular assist device. AB - The "washout effect" inside a blood pump may depend in part on the configuration of the blood pump, including its "port angle." The port angle, which is primarily decided based on anatomical considerations, may also be important from the rheological viewpoint. In our department, a next-generation diaphragm-type blood pump is being developed. In this study, we examined the influence of the port angle on flow conditions inside our new blood pump. Acrylic resin mock pumps with three different port angles (0 degrees , 30 degrees , and 45 degrees ) were prepared for flow visualization. Mechanical monoleaflet valves were mounted on the inlet and outlet ports of the mock pumps. Flow conditions within the mock pumps were visualized by means of particle image velocimetry during a half stroke. As a result, a high flow velocity region was seen along the main circular flow from the inlet to the outlet port. This circular flow was almost uniform and parallel to the plane of the diaphragm-housing junction (DhJ) when viewed from the inlet and outlet sides. Moreover, the proportion of high flow velocity vectors in the plane in the vicinity of the DhJ decreased as the degree of the port angle increased. In conclusion, we found that the flow behavior in the plane in the vicinity of the DhJ changed with the port angle, and that a port angle of 0 degrees may be suitable for our diaphragm-type blood pump in view of the washout effect. PMID- 22038497 TI - Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. AB - BACKGROUND: Tart Montmorency cherries have been reported to contain high levels of phytochemicals including melatonin, a molecule critical in regulating the sleep-wake cycle in humans. PURPOSE: The aim of our investigation was to ascertain whether ingestion of a tart cherry juice concentrate would increase the urinary melatonin levels in healthy adults and improve sleep quality. METHODS: In a randomised, double-blind, placebo-controlled, crossover design, 20 volunteers consumed either a placebo or tart cherry juice concentrate for 7 days. Measures of sleep quality recorded by actigraphy and subjective sleep questionnaires were completed. Sequential urine samples over 48 h were collected and urinary 6 sulfatoxymelatonin (major metabolite of melatonin) determined; cosinor analysis was used to determine melatonin circadian rhythm (mesor, acrophase and amplitude). In addition, total urinary melatonin content was determined over the sampled period. Trial differences were determined using a repeated measures ANOVA. RESULTS: Total melatonin content was significantly elevated (P < 0.05) in the cherry juice group, whilst no differences were shown between baseline and placebo trials. There were significant increases in time in bed, total sleep time and sleep efficiency total (P < 0.05) with cherry juice supplementation. Although there was no difference in timing of the melatonin circardian rhythm, there was a trend to a higher mesor and amplitude. CONCLUSIONS: These data suggest that consumption of a tart cherry juice concentrate provides an increase in exogenous melatonin that is beneficial in improving sleep duration and quality in healthy men and women and might be of benefit in managing disturbed sleep. PMID- 22038498 TI - Shared environmental contributions to substance use. AB - The current study examined the association between substance use in the household during childhood, parental attitudes towards substance use and lifetime substance use in males. Subjects included 1081 monozygotic and 707 dizygotic twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Retrospective reports of substance use and features of the family environment (adult household substance use and parental attitudes towards substance use) were obtained using a life history interview. A trivariate Cholesky decomposition was conducted using the program Mx to decompose common shared environmental variance. Findings suggest that family environmental factors accounted for a large proportion of the shared environmental effects for illicit drug use. Results illustrate an important way of extending behavior genetic research to reveal specific etiological environmental mechanisms. PMID- 22038499 TI - Diagnostic study and meta-analysis of C-reactive protein as a predictor of postoperative inflammatory complications after pancreatic surgery. AB - PURPOSE: Although C-reactive protein (CRP) can be measured by a standard blood test, its diagnostic value for distinguishing patients with inflammatory complications after pancreatic surgery from patients with normal postoperative inflammatory responses has not been adequately investigated. This study aimed to assess the diagnostic accuracy of CRP levels for the occurrence of postoperative inflammatory complications after pancreatic surgery. METHODS: Clinical data and CRP levels measured in 280 patients after pancreatic surgeries (performed between 1998 and 2010) until postoperative day 10 (POD 10) were retrospectively analyzed. Using the receiver operating characteristic method, diagnostic accuracy was evaluated by an area under the curve (AUC) analysis. Furthermore, the results of the present study were compared to previously published reports by applying diagnostic meta-analysis techniques. RESULTS: The 30-day mortality rate was 3.9% (95% CI 2.1-7.0%). Inflammatory complications occurred in 153 of 280 patients (54.6%; 95% CI 48.8-60.4%). On POD 4, the AUC was 0.67 (95% CI 0.58-0.76). The highest diagnostic accuracy was observed on POD 7 (AUC 0.77; 95% CI 0.68-0.85). In a diagnostic meta-analysis that included two additional studies, the diagnostic sensitivity on POD 4 was 0.63 (95% CI 0.50-0.76), and the specificity was 0.79 (95% CI 0.71-0.88). The highest sensitivity occurred on POD 6 (0.75; 95% CI 0.68-0.82). Considerable statistical heterogeneity was observed in the analysis of PODs 3, 4 and 5. CONCLUSION: According to this limited evidence, CRP levels had a low to moderate diagnostic accuracy. Large, blinded studies are warranted for a more precise estimation of CRP's diagnostic value. PMID- 22038500 TI - Evaluation of effects of a novel endoscopically applied radiofrequency ablation biliary catheter using an ex-vivo pig liver. AB - BACKGROUND: The effects of ablation with various settings of powers and times using a newly developed radiofrequency (RF) ablation device, the HabibTM EndoHPB catheter, are not well known. In the present study, we examined the effects of a novel RF ablation catheter using resected fresh pig livers and evaluated the macro- and microscopic effects of RF ablation under various conditions. MATERIALS AND METHODS: The RF application was performed step by step at 5, 10, 15, and 20 W power and 60, 90, 120 s, respectively. Macroscopic and microscopic findings of the ablation area were evaluated at each setting. RESULTS: The mean lengths of the short axis of the ablation area at 10 W and 60, 90 and 120 s were 8.0 +/- 1.0, 8.3 +/- 1.2, and 9.7 +/- 0.6 mm, respectively. The mean lengths of the long axis at 10 W power and 60, 90 and 120 s were 20.3 +/- 0.6, 21.3 +/- 1.6, and 28.3 +/- 2.1 mm, respectively. Although the lengths of the short and long axes at 5 and 10 W increased gradually with power, there were no obvious differences in either short or long axis lengths between 15 and 20 W. Of all the settings, only at 5 W and 60 and 90 s did the long axis of the ablation show separate areas around the 2 ring electrodes. CONCLUSIONS: Although other sequelae including hemorrhage, pancreatitis, acute inflammatory changes, perforation and late fibrosis could not be investigated in our ex-vivo pig model, our study clarified the relationship between ablation powers and times and the effects concerning depth and longitudinal spread of ablation. Although the clinical ablation setting at 7-10 W power and 2 min is suitable, ultimately the ablation power and time should be adjusted according to the size of masses using examples from the present results. PMID- 22038501 TI - Standard versus extended lymphadenectomy in radical pancreatoduodenectomy for ductal adenocarcinoma of the head of the pancreas: long-term results of a Japanese multicenter randomized controlled trial. AB - BACKGROUND: The value of pancreatoduodenectomy (PD) with extended lymphadenectomy for pancreatic cancer has been evaluated by many retrospective studies and 3 randomized controlled trials (RCT). However, the protocols used and the results found in the 3 RCTs were diverse. Therefore, a multicenter RCT was proposed in 1998 to evaluate the primary end point of long-term survival and the secondary end points of morbidity, mortality and quality of life of patients undergoing standard versus extended lymphadenectomy in radical PD for pancreatic cancer. METHODS: From March 2000 to May 2003, 112 patients with potentially curable pancreatic head cancer were enrolled and intraoperatively randomized to a standard or extended lymphadenectomy group. No resected patients received any adjuvant treatments. RESULTS: A hundred and one eligible patients were analyzed. Demographic and histopathological characteristics of the two groups were similar. The mean operating time, intraoperative blood loss and number of retrieved lymph nodes were greater in the extended group, but the other operative results were comparable. CONCLUSIONS: Although this multicenter RCT was conducted in a strict setting, extended lymphadenectomy in radical PD did not benefit long-term survival in patients with resectable pancreatic head cancer and led to levels of morbidity, mortality and quality of life comparable to those found after standard lymphadenectomy. PMID- 22038502 TI - Angiomatoid fibrous histiocytoma: pleomorphic variant associated with multiplication of EWSR1-CREB1 fusion gene. AB - Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor which exceptionally occurs in visceral organs or bones. Histologically this is a bland, monomorphic tumor and only occasionally shows pleomorphism. Vast majority of the soft tissue cases share the same translocation and the resulting EWSR1-CREB1 gene fusion as background pathogenetic alteration. Here we report a 10-year-old boy with subcutaneous tumor of the right shoulder. Histological, immunohistochemical and FISH analyses of the case revealed pleomorphic phenotype, characteristic immunophenotype and multiplication of the EWSR1-CREB1 fusion gene in the nuclei of the tumor cells. The possible explanation of the fusion gene multiplication, its relation to the morphology and the clinical outcome are discussed in the context of the published literature. PMID- 22038503 TI - An L1-regularized logistic model for detecting short-term neuronal interactions. AB - Interactions among neurons are a key component of neural signal processing. Rich neural data sets potentially containing evidence of interactions can now be collected readily in the laboratory, but existing analysis methods are often not sufficiently sensitive and specific to reveal these interactions. Generalized linear models offer a platform for analyzing multi-electrode recordings of neuronal spike train data. Here we suggest an L(1)-regularized logistic regression model (L(1)L method) to detect short-term (order of 3 ms) neuronal interactions. We estimate the parameters in this model using a coordinate descent algorithm, and determine the optimal tuning parameter using a Bayesian Information Criterion. Simulation studies show that in general the L(1)L method has better sensitivities and specificities than those of the traditional shuffle corrected cross-correlogram (covariogram) method. The L(1)L method is able to detect excitatory interactions with both high sensitivity and specificity with reasonably large recordings, even when the magnitude of the interactions is small; similar results hold for inhibition given sufficiently high baseline firing rates. Our study also suggests that the false positives can be further removed by thresholding, because their magnitudes are typically smaller than true interactions. Simulations also show that the L(1)L method is somewhat robust to partially observed networks. We apply the method to multi-electrode recordings collected in the monkey dorsal premotor cortex (PMd) while the animal prepares to make reaching arm movements. The results show that some neurons interact differently depending on task conditions. The stronger interactions detected with our L(1)L method were also visible using the covariogram method. PMID- 22038504 TI - Modulation of neurotransmitter release in orexin/hypocretin-2 receptor knockout mice: a microdialysis study. AB - Orexinergic neurons are discretely localized within the lateral hypothalamus and have widespread projections to the whole brain. Here, the role of orexin/hypocretin-2 receptors (OX2) in modulating extracellular concentrations of neurotransmitters was evaluated in the hypothalamus and the prefrontal cortex (PFC) of OX2 knockout (KO) mice by using a microdialysis technique. In the hypothalamus, basal concentrations of norephinephrine (NE), acetylcholine (ACh), and histamine (Hist) were significantly higher in KO mice, whereas KCl perfusion (147 mM) resulted in significantly lesser increases in NE, ACh, and Hist release in KO compared with wild-type (WT) mice. No differences in basal concentrations or evoked release of serotonin (5-HT) or dopamine (DA) were found in the hypothalamus between genotypes. In the PFC, no differences in the basal concentrations of the studied neurotransmitters were found between genotypes. After KCl perfusion, significantly higher increases in NE, 5-HT, and DA release were found in KO compared with WT mice. No differences in the evoked release of ACh and Hist in the PFC were found between genotypes. The present results demonstrate that genetic deletion of OX2 receptors differentially modulates extracellular concentrations of distinct neurotransmitters in the somatodendritic region vs. a nerve terminal region of the orexinergic neurons. In the hypothalamus, an inhibitory role of the OX2 receptors in modulating basal concentrations of NE, ACh, and Hist was revealed, which probably accounts for the reduced responsiveness to KCl as well. In the PFC, the evoked release of the monoamines NE, 5-HT, and DA seems to be controlled negatively by OX2 receptors. PMID- 22038505 TI - Effects of a Lactobacillus reuteri BR11 mutant deficient in the cystine-transport system in a rat model of inflammatory bowel disease. AB - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract associated with altered composition of the gut microbiota. Lactobacillus reuteri BR11 (BR11) has recently been reported to reduce the severity of experimental IBD because of its probiotic properties possibly attributed to a mechanism of thiol production via its unique cysteine/cystine-transport system. AIM: We compared BR11 and a BR11 mutant deficient in the cystine-uptake system (PNG201), for their capacity to reduce the severity of experimental colitis. METHODS: Male Sprague-Dawley rats (n = 8 per group) were gavaged (1 ml/day) with skim milk, BR11 or PNG201 (1 * 10(9) CFU/ml) for 12 days. Rats consumed either water or 2% dextran sulfate sodium in drinking water from days 6 to 12 to induce colitis. Metabolism data, disease activity index, intestinal mucin profile, and histological analyses were assessed and compared by ANOVA. RESULTS: Assessed histologically, DSS administration resulted in significant colonic deterioration, including loss of crypt area and increased damage severity. BR11 administration only partially alleviated the DSS effects, with a minor improvement in crypt area (P < 0.05). Administration of the PNG201 mutant strain to colitic animals failed to achieve significance (P > 0.05) against the DSS control for any of the end-points. However, the mutant strain induced significantly greater (P < 0.05) histological severity compared with BR11 treated colitic animals, indicative of possible exacerbation of colitis. CONCLUSIONS: The cystine-uptake system only minimally affects the biological effects of BR11, as evidenced by histological and macroscopic colitic changes. PMID- 22038506 TI - Reduced high-mobility group box 1 expression induced by RNA interference inhibits the bioactivity of hepatocellular carcinoma cell line HCCLM3. AB - BACKGROUND: Increased expression of high-mobility group box 1 (HMGB1) has been observed in many tumor types, but the role of HMGB1 in hepatocellular carcinoma (HCC) is unknown. AIMS: To examine the effects of RNA interference HMGB1 on the bioactivity of HCC cell line HCCLM3. METHODS: We synthesized three specific small interfering RNAs of HMGB1 (HMGB1-siRNAs) and transfected these into HCCLM3 cells by use of Lipofectamine 2000. RT-PCR and Western blot were performed to determine the effects of HMGB1-siRNAs on HMGB1 expression and to detect NF-kappaB/p65 and VEGF-C expression after transfection of HMGB1-siRNAs into HCCLM3. In vitro proliferation was assessed by MTT assay. Migration and invasive ability were determined by use of the Transwell assay. Apoptosis was demonstrated by flow cytometry. RESULTS: RT-PCR and Western blotting showed that all three specific HMGB1-siRNAs significantly inhibited HMGB1 expression, with inhibition by HMGB1 siRNA-1 being highest (70-80%). MTT assay demonstrated that the growth of cells transfected with HMGB1-siRNA-1 was significantly lower than that of control cells (P < 0.01). The Transwell assay showed that cell migration and invasion were significantly inhibited in HMGB1 knockdown cells compared with control cells (P < 0.01). FCM revealed that apoptosis was significantly increased in HMGB1-siRNA-1 transfected cells compared with control cells (P < 0.01). Expression of NF kappaB/p65 and VEGF-C was inhibited in HCCLM3 cells transfected with HMGB1-siRNA 1 compared with control cells (P < 0.01). CONCLUSION: Downregulation of HMGB1 could obviously inhibit the growth of HCCLM3 cells, and their migration and invasion ability. HMGB1 may serve as a potential target for treatment of HCC. PMID- 22038507 TI - Glutamine and whey protein improve intestinal permeability and morphology in patients with Crohn's disease: a randomized controlled trial. AB - BACKGROUND: Increased intestinal permeability (IP) has been implicated in the etiopathogenesis, disease activity and relapse of Crohn's disease (CD). Glutamine, the major fuel for the enterocytes, may improve IP. AIM: We evaluated the effect of oral glutamine on IP and intestinal morphology in patients with CD. METHODS: In a randomized controlled trial, consecutive patients with CD in remission phase with an abnormal IP were randomized to a glutamine group (GG) or active control group (ACG) and were given oral glutamine or whey protein, respectively, as 0.5 g/kg ideal body weight/day for 2 months. IP was assessed by the lactulose mannitol excretion ratio (LMR) in urine, and morphometry was performed by computerized image analysis system. RESULTS: Patients (age 34.5 +/- 10.5 years; 20 males) were assigned to the GG (n = 15) or ACG (n = 15). Fourteen patients in each group completed the trial. The LMR [median (range)] in GG and ACG at 2 months was 0.029 (0.006-0.090) and 0.033 (0.009-0.077), respectively, with P = 0.6133. IP normalized in 8 (57.1%) patients in each group (P = 1.000). The villous crypt ratio (VCR) [mean (SD)] in GG and ACG at 2 months was 2.68 (1.02) and 2.49 (0.67), respectively, (P = 0.347). At the end of 2 months LMR improved significantly in GG from 0.071 (0.041-0.254) to 0.029 (0.006-0.090) (P = 0.0012) and in ACG from 0.067 (0.040-0.136) to 0.033 (0.009-0.077) (P = 0.0063). VCR improved in the GG from 2.33 (0.77) to 2.68 (1.02) (P = 0.001), and in ACG from 2.26 (0.57) to 2.49 (0.67) (P = 0.009). CONCLUSIONS: Intestinal permeability and morphology improved significantly in both glutamine and ACG. PMID- 22038508 TI - Clinicopathologic features of advanced gallbladder cancer associated with adenomyomatosis. AB - Adenomyomatosis of the gallbladder has not been considered to have malignant potential, but gross features of adenomyomatosis are sometimes encountered in gallbladders resected under a diagnosis of gallbladder carcinoma. The purpose of this study was to determine the clinicopathologic features and survival rates in cases of gallbladder cancer with gross features of adenomyomatosis. The study subjects were 97 surgically treated gallbladder carcinoma patients. Only gallbladder showing typical gross features of adenomyomatosis was judged as adenomyomatosis-positive gallbladder cancer. In terms of gross findings, 25 cases (25.8%) were classified as adenomyomatosis-positive. The status of adenomyomatosis was significantly associated with the T stage (P=0.0004), lymph node (LN) metastasis (P<0.0001), distant metastasis (P=0.008), and stage (P=0.0005). In the adenomyomatosis-positive group, 16 of the 25 cases (64.0%) were classified as segmental type and 9 cases (36.0%) were classified as fundal type. No diffuse-type cases were present in this series. The status of adenomyomatosis correlated significantly with survival (P=0.0007). However, the multivariate analysis of significant variables identified from the univariate analysis identified only T stage (P=0.0178) and LN metastasis (P=0.0048) as independent prognostic factors. Subset analysis with T stage according to the status of adenomyomatosis showed no significant impact on survival. These results indicate that adenomyomatosis-positive gallbladder cancer is more often diagnosed clinically in the advanced stages. Since preceding adenomyomatosis may prevent the early detection of gallbladder cancer, the usefulness of preventive cholecystectomy in cases of asymptomatic adenomyomatosis should be considered. PMID- 22038509 TI - Frequency and clinical significance of placental histological lesions in an unselected population at or near term. AB - Associations between specific placental histological abnormalities and obstetric outcomes are reported. However, most data are based either on high-risk cases or relate to case-control studies selected from those with abnormal placental histology findings, with the unavoidable biases that these approaches entail. This study reports the frequency of the several common, objective and predefined histological abnormalities of the placenta as identified by pathologists blinded to all clinical information. A total 1,153 women were recruited from an unselected population delivering at 34-43 weeks. Histological findings in common obstetric outcome groups were compared to those of the unselected population, and odds ratios and predictive values were calculated. Normal histological findings were present in 72.1% of pregnancies with normal outcomes and in 79.1%, 66.6%, 80%, and 74.8% of pregnancies affected by pre-eclampsia (PET), pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small for gestational age (SGA), respectively. Chronic placental underperfusion was seen more frequently in PIH (odds ratio (OR) 2) and SGA (OR 1.4), while villitis of unknown aetiology was observed more commonly in cases with PIH (OR 3.2). Fetal thrombotic vasculopathy was twice as common in cases with GDM whilst massive perivillous fibrin deposition was much more frequent in those with PET (OR 20.2) and SGA (OR 8.9). Chorangiomata were 13 times more common in pregnancies with PET. However, in all cases, positive predictive values were low, with the majority of cases with histological abnormalities being associated with normal outcome. At term, specific placental histological lesions are significantly more common in complicated pregnancies, but the clinical significance of such lesions in a specific case remains uncertain, since the majority will be identified from clinically uncomplicated normal pregnancies. PMID- 22038510 TI - StavroX--a software for analyzing crosslinked products in protein interaction studies. AB - Chemical crosslinking in combination with mass spectrometry has matured into an alternative approach to derive low-resolution structural information of proteins and protein complexes. Yet, one of the major drawbacks of this strategy remains the lack of software that is able to handle the large MS datasets that are created after chemical crosslinking and enzymatic digestion of the crosslinking reaction mixtures. Here, we describe a software, termed StavroX, which has been specifically designed for analyzing highly complex crosslinking datasets. The StavroX software was evaluated for three diverse biological systems: (1) the complex between calmodulin and a peptide derived from Munc13, (2) an N-terminal beta-laminin fragment, and (3) the complex between guanylyl cyclase activating protein-2 and a peptide derived from retinal guanylyl cyclase. We show that the StavroX software is advantageous for analyzing crosslinked products due to its easy-to-use graphical user interface and the highly automated analysis of mass spectrometry (MS) and tandem mass spectrometry (MS/MS) data resulting in short times for analysis. StavroX is expected to give a further push to the chemical crosslinking approach as a routine technique for protein interaction studies. PMID- 22038511 TI - Methods and value of home uroflowmetry in the assessment of men with lower urinary tract symptoms: a literature review. AB - AIMS: Uroflowmetry is a key clinical assessment for men with LUTS. Home uroflowmetry is a convenient way to obtain multiple flow readings and has the potential to combat problems inherent to clinic-based measurements. We reviewed current evidence regarding the technology and value of multiple and home uroflowmetry. METHODS: We searched PubMed and Embase from January 1988 to February 2011 using a predetermined strategy. Reference lists from retrieved articles were scanned and additional papers screened for relevance. Proceedings of the annual meetings of the International Continence Society since 2008 were also searched. Relevant guidelines were obtained from the UK NHS Evidence repository. RESULTS: Eight studies described five simple, low-cost instruments giving multiple representative estimates of Q(max) but not a complete flow curve. A further eight studies described home use of four sophisticated, electronic flowmeters similar to clinic-based equipment. The above methods were assessed against ICS recommendations for uroflowmetry and the results of several studies investigating variability of flow parameters such as Q(max) were presented. CONCLUSIONS: Our findings illustrate the gulf between low-cost methods of obtaining average or peak flow measurements and precise, expensive devices with the capabilities of clinic flowmeters. Further studies are required to confirm the statistical benefit of averaging multiple values of Q(max) and to investigate the diagnostic and predictive value of flow variables other than Q(max) that can be derived from multiple recordings. PMID- 22038512 TI - Image data sharing for biomedical research--meeting HIPAA requirements for De identification. AB - Data sharing is increasingly recognized as critical to cross-disciplinary research and to assuring scientific validity. Despite National Institutes of Health and National Science Foundation policies encouraging data sharing by grantees, little data sharing of clinical data has in fact occurred. A principal reason often given is the potential of inadvertent violation of the Health Insurance Portability and Accountability Act privacy regulations. While regulations specify the components of private health information that should be protected, there are no commonly accepted methods to de-identify clinical data objects such as images. This leads institutions to take conservative risk-averse positions on data sharing. In imaging trials, where images are coded according to the Digital Imaging and Communications in Medicine (DICOM) standard, the complexity of the data objects and the flexibility of the DICOM standard have made it especially difficult to meet privacy protection objectives. The recent release of DICOM Supplement 142 on image de-identification has removed much of this impediment. This article describes the development of an open-source software suite that implements DICOM Supplement 142 as part of the National Biomedical Imaging Archive (NBIA). It also describes the lessons learned by the authors as NBIA has acquired more than 20 image collections encompassing over 30 million images. PMID- 22038513 TI - Influence of radiology report format on reading time and comprehension. AB - This study examined whether radiology report format influences reading time and comprehension of information. Three reports were reformatted to conventional free text, structured text organized by organ system, and hierarchical structured text organized by clinical significance. Five attending radiologists, five radiology residents, five internal medicine attendings, and five internal medicine residents read the reports and answered a series of questions about them. Reading was timed and participants reported reading preferences. For reading time, there was no significant effect for format, but there was for attending versus resident, and radiology versus internal medicine. For percent correct scores, there was no significant effect for report format or for attending versus resident, but there was for radiology versus internal medicine with the radiologists scoring better overall. Report format does not appear to impact viewing time or percent correct answers, but there are differences in both for specialty and level of experience. There were also differences between the four groups of participants with respect to what they focus on in a radiology report and how they read reports (skim versus read in detail). There may not be a "one size-fits-all" radiology report format as individual preferences differ widely. PMID- 22038514 TI - Automated detection of critical results in radiology reports. AB - The goal of this study was to develop and validate text-mining algorithms to automatically identify radiology reports containing critical results including tension or increasing/new large pneumothorax, acute pulmonary embolism, acute cholecystitis, acute appendicitis, ectopic pregnancy, scrotal torsion, unexplained free intraperitoneal air, new or increasing intracranial hemorrhage, and malpositioned tubes and lines. The algorithms were developed using rule-based approaches and designed to search for common words and phrases in radiology reports that indicate critical results. Certain text-mining features were utilized such as wildcards, stemming, negation detection, proximity matching, and expanded searches with applicable synonyms. To further improve accuracy, the algorithms utilized modality and exam-specific queries, searched under the "Impression" field of the radiology report, and excluded reports with a low level of diagnostic certainty. Algorithm accuracy was determined using precision, recall, and F-measure using human review as the reference standard. The overall accuracy (F-measure) of the algorithms ranged from 81% to 100%, with a mean precision and recall of 96% and 91%, respectively. These algorithms can be applied to radiology report databases for quality assurance and accreditation, integrated with existing dashboards for display and monitoring, and ported to other institutions for their own use. PMID- 22038515 TI - Ubiquitin C-terminal hydrolase L1 is required for pancreatic beta cell survival and function in lipotoxic conditions. AB - AIMS/HYPOTHESIS: Ubiquitin C-terminal hydrolase L1 (UCHL1) is associated with neurodegenerative diseases and has been suggested to have roles in pancreatic beta cells. Our proteomic analysis revealed that UCHL1 was the most increased protein in MIN6 cells exposed to palmitate. The present study used a genetic loss of-function model to test the hypothesis that UCHL1 is required for normal beta cell function and fate under lipotoxic conditions. METHODS: Human islets, mouse islets and MIN6 cells were used to analyse UCHL1 protein levels and regulation of UCHL1 by palmitate. The levels of free mono-ubiquitin and poly-ubiquitinated proteins were assessed. Gracile axonal dystrophy (GAD) mutant mice lacking UCHL1 were fed a normal or lipotoxic high-fat diet. Glucose tolerance, insulin tolerance and insulin secretion were assessed in vivo. Beta cell death and proliferation were assessed by TUNEL and proliferating cell nuclear antigen (PCNA) staining. Insulin secretion, calcium signalling, endoplasmic reticulum (ER) stress, apoptosis and SNARE protein levels were assessed in vitro. RESULTS: UCHL1 protein, which was highly specific to beta cells, was increased by palmitate at basal glucose, but not in the context of hyperglycaemia associated with frank diabetes. Although islet development and function were initially normal in Uchl1 (-/-) mice, a 4-week high-fat diet caused glucose intolerance and impaired insulin secretion. Uchl1 (-/-) mice had increased ER stress and beta cell apoptosis. The levels of SNARE proteins were dysregulated in Uchl1 (-/-) islets. Palmitate-stimulated vesicle-associated membrane protein 2 (VAMP2) ubiquitination was modulated by a chemical UCHL1 inhibitor. CONCLUSIONS/INTERPRETATION: Together, these data suggest that UCHL1 has essential functional and anti-apoptotic roles in beta cells under stress conditions associated with lipotoxicity. PMID- 22038516 TI - cJUN N-terminal kinase (JNK) activation mediates islet amyloid-induced beta cell apoptosis in cultured human islet amyloid polypeptide transgenic mouse islets. AB - AIMS/HYPOTHESIS: Aggregation of human islet amyloid polypeptide (hIAPP) as islet amyloid is associated with increased beta cell apoptosis and reduced beta cell mass in type 2 diabetes. Islet amyloid formation induces oxidative stress, which contributes to beta cell apoptosis. The cJUN N-terminal kinase (JNK) pathway is a critical mediator of beta cell apoptosis in response to stress stimuli including oxidative stress and exogenous application of hIAPP. We determined whether amyloid formation by endogenous hIAPP mediates beta cell apoptosis through JNK activation and downstream signalling pathways. METHODS: hIAPP transgenic and non transgenic mouse islets were cultured for up to 144 h in 16.7 mmol/l glucose to induce islet amyloid in the presence or absence of the amyloid inhibitor Congo Red or a cell-permeable JNK inhibitor. Amyloid, beta cell apoptosis, JNK signalling and activation of downstream targets in the intrinsic and extrinsic apoptotic pathways were measured. RESULTS: JNK activation occurred with islet amyloid formation in hIAPP transgenic islets after 48 and 144 h in culture. Neither high glucose nor the hIAPP transgene alone was sufficient to activate JNK independent of islet amyloid. Inhibition of islet amyloid formation with Congo Red reduced beta cell apoptosis and partially decreased JNK activation. JNK inhibitor treatment reduced beta cell apoptosis without affecting islet amyloid. Islet amyloid increased mRNA levels of markers of the extrinsic (Fas, Fadd) and intrinsic (Bim [also known as Bcl2l11]) apoptotic pathways, caspase 3 and the anti-apoptotic molecule Bclxl (also known as Bcl2l1) in a JNK-dependent manner. CONCLUSIONS/INTERPRETATION: Islet amyloid formation induces JNK activation, which upregulates predominantly pro-apoptotic signals in both extrinsic and intrinsic pathways, resulting in beta cell apoptosis. PMID- 22038517 TI - A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus. AB - AIMS/HYPOTHESIS: We carried out a urinary metabolomic study to gain insight into low estimated GFR (eGFR) in patients with non-proteinuric type 2 diabetes. METHODS: Patients were identified as being non-proteinuric using multiple urinalyses. Cases (n = 44) with low eGFR and controls (n = 46) had eGFR values <60 and >=60 ml min(-1) 1.73 m(-2), respectively, as calculated using the Modification of Diet in Renal Disease formula. Urine samples were analysed by liquid chromatography/mass spectrometry (LC/MS) and GC/MS. False discovery rates were used to adjust for multiple hypotheses testing, and selection of metabolites that best predicted low eGFR status was achieved using least absolute shrinkage and selection operator logistic regression. RESULTS: Eleven GC/MS metabolites were strongly associated with low eGFR after correction for multiple hypotheses testing (smallest adjusted p value = 2.62 * 10(-14), largest adjusted p value = 3.84 * 10(-2)). In regression analysis, octanol, oxalic acid, phosphoric acid, benzamide, creatinine, 3,5-dimethoxymandelic amide and N-acetylglutamine were selected as the best subset for prediction and allowed excellent classification of low eGFR (AUC = 0.996). In LC/MS, 19 metabolites remained significant after multiple hypotheses testing had been taken into account (smallest adjusted p value = 2.04 * 10(-4), largest adjusted p value = 4.48 * 10(-2)), and several metabolites showed stronger evidence of association relative to the uraemic toxin, indoxyl sulphate (adjusted p value = 3.03 * 10(-2)). The potential effect of confounding on the association between metabolites was excluded. CONCLUSIONS/INTERPRETATION: Our study has yielded substantial new insight into low eGFR and provided a collection of potential urinary biomarkers for its detection. PMID- 22038518 TI - Coupling factor 6-induced activation of ecto-F1F(o) complex induces insulin resistance, mild glucose intolerance and elevated blood pressure in mice. AB - AIMS/HYPOTHESIS: Despite advances in pharmacological treatments, diabetes with hypertension continues to be a major public health problem with high morbidity and mortality rates. We recently identified a circulating peptide coupling factor 6 (CF6), which binds to the plasma membrane ATP synthase (ecto-F(1)F(o) complex), resulting in intracellular acidosis. We investigated whether overexpression of CF6 contributes to diabetes and hypertension by intracellular acidosis. METHODS: Transgenic mice overexpressing CF6 (also known as ATP5J) were generated, and physiological, biochemical and molecular biology studies were performed. RESULTS: CF6 overexpression elicited a sustained decrease in intracellular pH in tissues (aorta, kidney, skeletal muscle and liver, with the exception of adipose tissue) that express its receptor, the beta-subunit of ecto-F(1)F(o) complex. Consistent with the receptor distribution, phospho-insulin receptor beta, phosphoinositide 3 kinase activity and the phospho-Akt1:total Akt1 ratio were all decreased in the skeletal muscle and the liver in transgenic compared with wild-type mice, resulting in a decrease of plasma membrane-bound GLUT4 and an increase in hepatic glucose production. Under a high-sucrose diet, transgenic mice had insulin resistance and mild glucose intolerance; under a high-salt diet, they had elevated blood pressure with increased renal RAS-related C3 botulinum substrate 1 (RAC1)-GTP, which is an activator of mineralocorticoid receptor. CONCLUSIONS/INTERPRETATION: Through its action on the beta-subunit of ecto F(1)F(o) complex, which results in intracellular acidosis, CF6 plays a crucial role in the development of insulin resistance and hypertension. This finding might advance our understanding of the mechanisms underlying diabetes and hypertension, possibly also providing a novel therapeutic target against cardiovascular disease. PMID- 22038519 TI - Immunohistochemical characterisation of cells co-producing insulin and glucagon in the developing human pancreas. AB - AIMS/HYPOTHESIS: In adult human islets, insulin and glucagon production is largely restricted to individual cell populations. The production of these hormones is less segregated during development and during the differentiation of human pluripotent stem cells towards pancreatic lineages. We therefore sought to characterise the transcription factor profile of these cells that co-produce insulin and glucagon in the developing human pancreas, and thus to gain insight into their potential fate during normal pancreas development. METHODS: An immunohistochemical analysis was performed on human pancreas sections from fetal donors aged 9 to 21 weeks and from adult donors between the ages of 17 and 55 years. RESULTS: Endocrine cells were observed within the pancreas at all ages examined, with cells co-producing insulin and glucagon observed as early as 9 weeks of fetal age. The population of cells that co-produce insulin and glucagon generally decreased in prevalence with age, with negligible numbers in adult pancreas. From 9 to 16 weeks, the population of glucagon-only cells increased, while the insulin-only cells decreased in abundance. Cells that co-produced insulin and glucagon also produced the alpha cell transcription factor, aristaless related homeobox (ARX), and lacked the beta cell transcription factors pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1) and v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA). CONCLUSIONS/INTERPRETATION: Our results indicate that cells co-producing insulin and glucagon in the developing human pancreas share a transcription factor profile that is similar to that of mature alpha cells and suggest that some maturing alpha cells briefly exhibit ectopic insulin expression. Thus cells that co-produce insulin and glucagon may represent a transient cell population, which gives rise to mature alpha cells. PMID- 22038521 TI - Remembering our classics: then and now. PMID- 22038520 TI - Cellular characterisation of the GCKR P446L variant associated with type 2 diabetes risk. AB - AIMS/HYPOTHESIS: Translation of genetic association signals into molecular mechanisms for diabetes has been slow. The glucokinase regulatory protein (GKRP; gene symbol GCKR) P446L variant, associated with inverse modulation of glucose- and lipid-related traits, has been shown to alter the kinetics of glucokinase (GCK) inhibition. As GCK inhibition is associated with nuclear sequestration, we aimed to determine whether this variant also alters the direct interaction between GKRP and GCK and their intracellular localisation. METHODS: Fluorescently tagged rat and human wild-type (WT)- or P446L-GCKR and GCK were transiently transfected into HeLa cells and mouse primary hepatocytes. Whole-cell and nuclear fluorescence was quantified in individual cells exposed to low- or high-glucose conditions (5.5 or 25 mmol/l glucose, respectively). Interaction between GCK and GKRP was measured by sensitised emission-based fluorescence resonance energy transfer (FRET) efficiency. RESULTS: P446L-GKRP had a decreased degree of nuclear localisation, ability to sequester GCK and direct interaction with GCK as measured by FRET compared with WT-GKRP. Decreased interaction was observed between WT-GKRP and GCK at high compared with low glucose, but not between P446L GKRP and GCK. Rat WT-GKRP and P446L-GKRP behaved quite differently: both variants responded to high glucose by diminished sequestration of GCK but showed no effect of the P446L variant on nuclear localisation or GCK sequestration. CONCLUSIONS/INTERPRETATION: Our study suggests the common human P446L-GKRP variant protein results in elevated hepatic glucose uptake and disposal by increasing active cytosolic GCK. This would increase hepatic lipid biosynthesis but decrease fasting plasma glucose concentrations and provides a potential mechanism for the protective effect of this allele on type 2 diabetes risk. PMID- 22038522 TI - Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism. AB - AIMS/HYPOTHESIS: Common genetic variants have been associated with type 2 diabetes. We hypothesised that a subset of these variants may have different effects on the transition from normal fasting glucose (NFG) to impaired fasting glucose (IFG) than on that from IFG to diabetes. METHODS: We identified 16 type 2 diabetes risk variants from the Illumina Broad Candidate-gene Association Resource (CARe) array genotyped in 26,576 CARe participants. Participants were categorised at baseline as NFG, IFG or type 2 diabetic (n = 16,465, 8,017 or 2,291, respectively). Using Cox proportional hazards and likelihood ratio tests (LRTs), we compared rates of progression by genotype for 4,909 (NFG to IFG) and 1,518 (IFG to type 2 diabetes) individuals, respectively. We then performed multinomial regression analyses at baseline, comparing the risk of assignment to the NFG, IFG or diabetes groups by genotype. RESULTS: The rate of progression from NFG to IFG was significantly greater in participants carrying the risk allele at MTNR1B (p = 1 * 10(-4)), nominally greater at GCK and SLC30A8 (p < 0.05) and nominally smaller at IGF2BP2 (p = 0.01) than the rate of progression from IFG to diabetes by the LRT. Results of the baseline, multinomial regression model were consistent with these findings. CONCLUSIONS/INTERPRETATION: Common genetic risk variants at GCK, SLC30A8, IGF2BP2 and MTNR1B influence to different extents the development of IFG and the transition from IFG to type 2 diabetes. Our findings may have implications for understanding the genetic contribution of these variants to the development of IFG and type 2 diabetes. PMID- 22038524 TI - Antidepressant drug use and future diabetes risk. PMID- 22038525 TI - Brain biochemistry in autopsied patients with essential tremor. AB - The pathology of essential tremor is increasingly being studied; however, there are limited studies of biochemical changes in this condition. We studied several candidate biochemical/anatomical systems in the brain stem, striatum, and cerebellum of 23 essential tremor subjects who came to autopsy, comparing them with a control population. Striatal tyrosine hydroxylase, a marker of dopaminergic neurons, was 91.7 +/- 113.2 versus 96.4 +/- 102.7 ng/mg (not significant) in cases and controls, respectively. Locus coeruleus dopamine beta hydroxylase, a marker of noradrenergic neurons, was not significantly different between the essential tremor and control groups. Parvalbumin, a marker of GABAergic neurons, was 199.3 +/- 42.0 versus 251.4 +/- 74.8 ng/mg (P = .025) in the pons in the region of the locus coeruleus of essential tremor subjects versus controls, whereas there was no difference in cerebellar parvalbumin. These results are supportive of a possible role for reduced GABAergic function in the locus coeruleus in essential tremor. The hypothesis that essential tremor represents early Parkinson's disease was not supported, as striatal dopaminergic markers were not reduced compared with control subjects. PMID- 22038526 TI - Estimation of cumulative incidence functions when the lifetime distributions are uniformly stochastically ordered. AB - In the competing risks problem an important role is played by the cumulative incidence function (CIF), whose value at time t is the probability of failure by time t from a particular type of risk in the presence of other risks. Assume that the lifetime distributions of two populations are uniformly stochastically ordered. Since this ordering may not hold for the empiricals due to sampling variability, it is natural to estimate these distributions under this constraint. This will in turn affect the estimation of the CIFs. This article considers this estimation problem. We do not assume that the risk sets in the two populations are related, give consistent estimators of all the CIFs and study the weak convergence of the resulting processes. We also report the results of a simulation study that show that our restricted estimators outperform the unrestricted ones in terms of mean square error. A real life example is used to illustrate our theoretical results. PMID- 22038527 TI - Human immune system mice: current potential and limitations for translational research on human antibody responses. AB - It has recently become possible to generate chimeric mice durably engrafted with many components of the human immune system (HIS mice). We have characterized the maturation and function of the B cell compartment of HIS mice. The antibody response of HIS mice to T cell-dependent B cell antigens is limited, and contributing factors may be the general immaturity of the B cell compartment, infrequent helper T cells selected on human MHC class II antigens, and incomplete reconstitution of secondary lymphoid organs and their microenvironments. In contrast, HIS mice generate protective antibody responses to the bacterium Borrelia hermsii, which acts as a T cell-independent antigen in mice, but do not respond to purified polysaccharide antigens (PPS). We speculate that the anti-B. hermsii response of HIS mice is derived from an abundant B cell subset that may be analogous to B1 B cells in mice. We suggest that failure of HIS mice to respond to PPS is due to the lack of a B cell subset that may originate from adult bone marrow and is highly dependent on human interleukin-7 for development. PMID- 22038528 TI - Impaired clearance of apoptotic cells in germinal centers: implications for loss of B cell tolerance and induction of autoimmunity. AB - Germinal centers (GCs) comprise lymphoid microenvironments where antigen stimulated B cells undergo rapid proliferation and somatic hypermutation (SHM), resulting in the generation of B cells with high affinity for antigen. However, this process also generates B cell clones with low antigen affinity and with the potential for autoreactivity. It has been suggested that GC B cells with low antigen affinity and autoreactivity are eliminated via apoptosis and are rapidly cleared by tingible body macrophages (TBMphis). Inefficient clearance of apoptotic cells (ACs) results in autoimmunity that is thought to be mediated by various intracellular molecules possessing danger-associated molecular patterns (DAMPs), including nuclear self-Ags. DAMPs can be released from ACs undergoing "secondary necrosis" due to a disruption in AC clearance within GCs. This review discusses the role and mechanisms associated with impaired clearance of ACs in GCs in loss of B cell tolerance leading to autoantibody production and the development of autoimmunity. PMID- 22038529 TI - RIP1-mediated regulation of lymphocyte survival and death responses. AB - RIP1 is an adaptor serine/threonine kinase associated with the signaling complex of death receptors (DRs) including Fas, TNFR1, and TRAIL-Rs which can initiate apoptosis. While DRs are dispensable throughout development, RIP1 deletion results in perinatal lethality. The developmental defect caused by absence of RIP1 remains unexplained. In previous studies, RIP1-deficient hematopoietic progenitors failed to reconstitute the T cell compartment and our recent data indicate a new role for RIP1 in TCR-induced activation of the pro-survival NF kappaB pathway. Here, we show that RIP1 is also critical for B cell development. In addition, RIP1(-/-) B cells stimulated through LPS/TLR4 are impaired in NF kappaB activation but have no major defect in the Akt pathway. Recently, RIP1 has also emerged as a critical player in necrosis-like death, necroptosis, in various cell lines. We have demonstrated that RIP1 deficiency can reverse the embryonic and T cell proliferation defects in mice lacking FADD, a caspase adaptor protein, which indicates a potential role for RIP1 in mediating in vivo necroptosis. We provide an overview and discussion of the accumulating data revealing insights into the diverse functions of RIP1 in survival and death signaling in lymphocytes. PMID- 22038531 TI - Long-term follow-up of prophylactic implantable cardioverter-defibrillator-only therapy: comparison of ischemic and nonischemic heart disease. AB - BACKGROUND: The benefits of primary prophylactic implantable cardioverter defibrillators (ICDs) are actually debated, as some drawbacks become more apparent and as the natural history of cardiac disease seems to improve. Therefore, contemporary follow-up data of non-trial populations treated according to current guidelines remain necessary. The aim of this study was to evaluate mortality and the occurrence of ICD interventions in patients with coronary artery disease (CAD) and dilated cardiomyopathy (DCM) who received in the recent era a primary prophylactic ICD without resynchronization therapy. HYPOTHESIS: Survival and event-free rates from appropriate ICD therapy are different between ischemic and nonischemic ICD patients. METHODS: Prospective cohort study of 427 consecutive primary prevention ICD patients with ischemic or nonischemic heart disease, excluding patients with resynchronization. RESULTS: Ischemic heart disease was present in 290 patients (68%), nonischemic heart disease in 137 patients (32%). During a median follow-up of 31 months (interquartile range [IQR] 15-45 months), 30 patients (7%) died. Mortality was not different in both disease categories. The incidence of appropriate ICD interventions was similar in CAD and DCM (23% vs 21%). Appropriate ICD intervention occurred more frequently in patients with atrial fibrillation (29% vs 19%). Inappropriate ICD intervention occurred in 11% of patients. CONCLUSIONS: The clinical course of ischemic and nonischemic heart disease patients treated with a primary prophylactic ICD is similar with respect to mortality and to appropriate and inappropriate ICD interventions, in spite of a younger age at baseline of the DCM patients. PMID- 22038530 TI - GUCY2C-targeted cancer immunotherapy: past, present and future. AB - For the last decade, we have focused on guanylyl cyclase C (GUCY2C) as a potentially ideal target antigen for colorectal cancer immunotherapy. GUCY2C is expressed only in intestinal epithelial cells and by nearly 100% of colorectal cancers. We have developed and tested a recombinant adenoviral vector possessing GUCY2C (Ad5-GUCY2C) as a candidate vaccine for colorectal cancer patients. Murine studies have revealed that this vaccine is safe and effective against GUCY2C expressing targets, and Ad5-GUCY2C is poised for phase I clinical testing in colorectal cancer patients with minimal residual disease. Moreover, we are developing second-generation GUCY2C-targeted therapeutics, including the use of chimeric antigen receptor (CAR)-expressing T cells, for treatment of patients with advanced colorectal cancer for whom Ad5-GUCY2C immunization is not appropriate. Thus, a family of GUCY2C-targeted immunotherapeutics may bridge the gap in effective treatments for the 500,000 patients worldwide who die annually from colorectal cancer. PMID- 22038532 TI - Randomized clinical trial of a brief psychological intervention to increase walking in patients with intermittent claudication. AB - BACKGROUND: Increased walking is often recommended for patients with intermittent claudication (IC). Current methods to increase walking in these patients increase capability but not daily behaviour. This trial assessed whether a brief psychological intervention could increase daily walking at 4 months. METHODS: This randomized, single-centre, parallel-group trial was conducted between April 2008 and July 2010. Patients newly diagnosed with IC were randomly assigned into two groups. All clinical staff involved in patient management were blinded to allocation. The control group received usual care plus researcher contact, and the treatment group received usual care and a brief psychological intervention to modify illness and walking beliefs and to develop a personalized walking action plan. The psychological intervention was delivered in two 1-h sessions in participants' homes. The primary outcome was daily steps measured by pedometer 4 months later. Analyses were by intention to treat. RESULTS: Of 109 patients screened, 72 were eligible for inclusion; 58 patients consented to participate and were randomly allocated to usual care (30) or brief psychological intervention (28). All 58 participants were included in the analysis of the primary outcome. Compared with controls at 4-month follow-up, participants who received the psychological intervention walked a mean of 1575.63 (95 per cent confidence interval 731.97 to 2419.29) more steps per day. There were no adverse events. CONCLUSION: A brief psychological intervention significantly increased daily walking in patients with IC at 4 months. This study provided support for a potentially new direction in the treatment of IC. REGISTRATION NUMBER: ISRCTN28051878 (http://www.controlled-trials.com). PMID- 22038533 TI - Evolution of lipid profiles after bariatric surgery. AB - BACKGROUND: The most commonly encountered dyslipidemia in obese individuals is characterized by a cluster of interrelated plasma lipid and lipoprotein abnormalities including hypertriglyceridemia, low HDL cholesterol values, and increased small, dense LDL cholesterol particles. The aim of this study was to assess the changes in lipid profiles at baseline (pre-operatively) and at follow up (6, 12, and 18 months) after a laparoscopic Roux-en-Y gastric bypass (LRYGBP). A retrospective observational study was performed involving all patients who consecutively underwent a LRYGBP between January 1, 2007 and December 31, 2009. Fasting lipids sub-fractions (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides) were measured and HOMA-IR calculated pre operatively and at follow-up post-LRYGBP. Pearson's correlation coefficients were used to assess the relationship between excess weight loss (EWL) and lipid sub fractions. ANOVA was used to assess the differences between each lipid sub fraction at various time-points. METHODS: One hundred twenty eight (N = 128) medical charts were reviewed, and those containing data on lipid fractions at the three follow-up time-points were analyzed. One hundred fourteen patients (N = 114), 84 of whom were women (73.7%), were finally included in the study. RESULTS: Total cholesterol, LDL cholesterol, triglycerides, and HOMA-IR were significantly reduced after LRYGBP (P < 0.0005 for all). Inversely, HDL cholesterol disclosed a significant rise (P < 0.0005). Noteworthy significant associations between lipid subfractions and EWL were detected overall (P < 0.0005 for all). A gender effect was found since female patients displayed a milder association than male patients (P < 0.0005). CONCLUSIONS: LRYGBP-induced weight loss improves the lipid profile while reducing insulin resistance, with male patients showing a better profile than female patients. PMID- 22038523 TI - Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial. AB - AIMS/OBJECTIVE: Conflicting data regarding cardiovascular effects of thiazolidinediones (TZDs) and extra-skeletal effects of vitamin D supported the need for a definitive trial. The Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) trial aimed to assess the effects of TZDs (rosiglitazone and pioglitazone) on cardiovascular outcomes and the effects of vitamin D (cholecalciferol) on cancers and mortality. METHODS: A large multicentre 3 * 2 factorial double-blind placebo-controlled randomised trial recruited from outpatient primary care and specialty clinics in 33 countries. From June 2009 to July 2010, 1,332 people with type 2 diabetes and other cardiovascular risk factors aged >= 50 years whose HbA(1c) was 6.5-9.5% (48-80 mmol/mol) when using two or fewer glucose-lowering drugs were randomised by a central computer system to placebo (n = 541), rosiglitazone 4-8 mg/day (n = 399) or pioglitazone 30-45 mg/day (n = 392); 1,221 participants were randomised to placebo (n = 614) or vitamin D 1,000 IU/day (n = 607). Participants and all study personnel were blind to treatment allocation. The primary outcome for the TZD arm was the composite of myocardial infarction, stroke or cardiovascular death, and for the vitamin D arm it was cancer or all-cause death. All randomised participants were included in the primary analysis. RESULTS: From the study design, 16,000 people were to be followed for approximately 5.5 years. However, the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data. In the TZD arm, the cardiovascular outcome occurred in five participants (0.9%) in the placebo groups and three participants (0.4%) in the TZD groups (two allocated to pioglitazone, one to rosiglitazone). In the vitamin D arm, the primary outcome occurred in three participants (0.5%) in the placebo group and in two participants (0.3%) receiving vitamin D. Adverse events were comparable in all groups. CONCLUSIONS/INTERPRETATION: Uncertainty persists regarding the clinically relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial. PMID- 22038534 TI - Effects of alpha7 nicotinic acetylcholine receptor agonists on antipsychotic efficacy in a preclinical mouse model of psychosis. AB - RATIONALE: Antipsychotics normalize responses in the DBA/2 mouse model of prepulse inhibition (PPI), a preclinical model of sensorimotor gating deficits. The alpha7 nicotinic acetylcholine receptor (nAChR) as a molecular target is considered an attractive approach for improvement of cognitive deficits in schizophrenia (CDS). Assessment of clinical efficacy of novel agents in CDS involves treating patients already on antipsychotic medications. OBJECTIVE: We evaluated the effects of the combination of alpha7 nAChR agonists ABT-107 (0.1 10.0 mg/kg i.p.), A-582941 (0.04-4.0 mg/kg i.p.), and PNU282987 (1.0-10.0 mg/kg i.p.) with risperidone (0.1-1.0 mg/kg i.p.) or haloperidol (0.3-3.0 mg/kg i.p.), representative atypical and typical antipsychotic agents in the DBA/2 mouse PPI model. The same alpha7 agonists were given alone or in combination with a dose of antipsychotic medication that induces a minimal level of catalepsy in rats, an assay with predictive validity for the induction of extrapyramidal symptoms. RESULTS: The alpha7 nAChR agonists ABT-107, A-582941, and PNU282987 had no effect in DBA/2 mouse PPI when given alone yet increased the effects of haloperidol and risperidone. The alpha7 nAChR agonists did not cause catalepsy in rats, nor did they enhance antipsychotic-induced catalepsy. CONCLUSIONS: When given in combination with either a typical or atypical antipsychotic, alpha7 nAChR agonists did not impair efficacy in the DBA/2 J mouse PPI model. The efficacy but not the motoric side effects of antipsychotics was enhanced, suggesting that adjunctive therapy of alpha7 nAChR agonists not only could be useful for the treatment of cognitive deficits associated with schizophrenia but also could enhance the efficacy against positive symptoms. PMID- 22038536 TI - Nicotine differentially modulates antisaccade performance in healthy male non smoking volunteers stratified for low and high accuracy. AB - RATIONALE: Nicotinergic agents are currently examined as possible pro-cognitive drugs for a variety of clinical conditions marked by cognitive deficits, such as attention deficit hyperactivity disorder (ADHD) or schizophrenia. The response to acute nicotine is heterogeneous across subjects and samples; however, only a few reliable predictors of response have been identified. OBJECTIVES: We tested the hypothesis that baseline performance level in cognitive control may be a predictor of the cognitive effects of nicotine. METHODS: We tested 28 healthy Caucasian, male, non-smoking volunteers with the antisaccade task, an oculomotor measure of cognitive control. Participants were given a 7-mg nicotine patch in a double-blind, placebo-controlled, counterbalanced, within-subjects design. Subjects were stratified into high and low performers based on their antisaccade error rate in the placebo condition (median split). RESULTS: Nicotine tended to reduce response time variability of prosaccade latency (p = 0.06). There was no main effect of nicotine on antisaccade error rate (p = 0.31). However, nicotine significantly reduced antisaccade error rate in the low-accuracy probands while leaving performance of the high-accuracy probands unaffected (interaction, p < 0.05). Furthermore, we found a nicotine-induced reduction of response time variability of antisaccade latency at one target location in the low-performing group (interaction, p < 0.05). CONCLUSIONS: The present results demonstrate the importance of baseline performance differences for the effectiveness of pharmacological enhancement of cognitive control. More generally, the results suggest that stimulation of the nicotinic acetylcholine receptor system might be an effective way of improving cognition in people with poor cognitive performance, such as patients with ADHD or schizophrenia. PMID- 22038535 TI - Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine. AB - RATIONALE: Cognitive deficits represent a core symptom cluster in schizophrenia (SZ) that is predictive of outcome but not effectively treated by current antipsychotics. Thus, there is a need for validated animal models for testing potential pro-cognitive drugs. OBJECTIVE: As kynurenic acid levels are increased in prefrontal cortex (PFC) of individuals with SZ, we acutely increased brain levels of this astrocyte-derived, negative modulator of alpha7 nicotinic acetylcholine receptors (alpha7nAChRs) by administration of its bioprecursor kynurenine and measured the effects on extracellular kynurenic acid and glutamate levels in PFC and also performance in a set-shifting task. RESULTS: Injections of kynurenine (100 mg/kg, i.p.) increased extracellular kynurenic acid (1,500%) and decreased glutamate levels (30%) in PFC. Kynurenine also produced selective deficits in set-shifting. Saline- and kynurenine-treated rats similarly acquired the compound discrimination and intra-dimensional shift (saline, 7.0 and 6.3 trials, respectively; kynurenine, 8.0 and 6.7). Both groups required more trials to acquire the initial reversal (saline, 15.3; kynurenine, 22.2). Only kynurenine treated rats were impaired in acquiring the extra-dimensional shift (saline, 8.2; kynurenine, 21.3). These deficits were normalized by administering the alpha7nAChR positive allosteric modulator galantamine (3.0 mg/kg, i.p) prior to kynurenine, as trials were comparable between galantamine + kynurenine (7.8) and controls (8.2). Bilateral local perfusion of the PFC with galantamine (5.0 MUM) also attenuated kynurenine-induced deficits. CONCLUSIONS: These results validate the use of animals with elevated brain kynurenic acid levels in SZ research and support studies of drugs that normalize brain kynurenic acid levels and/or positively modulate alpha7nAChRs as pro-cognitive treatments for SZ. PMID- 22038537 TI - MDMA induces Per1, Per2 and c-fos gene expression in rat suprachiasmatic nuclei. AB - RATIONALE: +/-3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a psychoactive drug that has marked effects on the serotonergic system. Serotonergic agonists are known to interact with the circadian pacemaker located in the suprachiasmatic nuclei (SCN). OBJECTIVES: Given changes reported in the behavioral activity rhythm following MDMA treatment, the effects of MDMA on core clock gene (Per1, Per2) and c-fos expression were evaluated. METHODS: Male Long Evans rats (n = 72) were injected once with MDMA (5 mg/kg i.p.) or saline either at the middle of their 'rest' phase (Zeitgeber Time: ZT6) or the middle of their 'active' phase (Zeitgeber Time: ZT16) and killed at 30, 60, or 120 min posttreatment for gene expression analysis in the SCN using PCR. Behavioral rhythms of a separate group of rats (n = 20) were measured following treatment at ZT16 while they were held in constant darkness for 10 days posttreatment. RESULTS: At ZT6, c-fos mRNA was significantly induced 120 min post-MDMA treatment but there were no significant changes in Per1 or Per2 mRNA expression. At ZT16, there were significant inductions of c-fos mRNA (30 and 60 min) and Per1 and Per2 mRNA (both 60 min) post-MDMA treatment. However, no differences in behavioral activity patterns were noted following MDMA treatment at ZT16. CONCLUSIONS: These data provide evidence that MDMA has time of day dependent actions on SCN functioning, as evident from its induction of core clock genes that are important for generating and maintaining circadian rhythmicity. PMID- 22038539 TI - A mechanism of immunoreceptor tyrosine-based activation motif (ITAM)-like sequences in the capsid protein VP2 in viral growth and pathogenesis of Coxsackievirus B3. AB - Coxsackievirus B3 (CVB3) is an RNA virus that mainly causes myocarditis. We have reported previously that immunoreceptor tyrosine-based activation motif (ITAM) like sequences are contained in the capsid protein VP2 of CVB3. The substitution of two tyrosines for phenylalanines in the ITAM-like region causes attenuation of CVB3, possibly via defective viral assembly. In this study, we found that Syk, a downstream molecule of ITAM, interacts with the wild-type (WT) CVB3 VP0 protein, but not with the mutant CVB3 VP0 (called YYFF), and that an inhibitor of Syk reduced the growth of CVB3. The WT CVB3 activated nuclear factor kappa B (NF kappaB), a protein activated by ITAM, and eventually induced the production of interleukin-6 (IL-6)-one of the proinflammatory cytokines induced by NF-kappaB-in macrophages. However, the YYFF form did not. In addition, viral VP2 protein may be dependent on the phosphorylation of an ITAM-like region that affected the activation of NF-kappaB. Taken together, these results suggest that the ITAM-like sequences in CVB3 VP2 can not only affect viral structure but also act as signals in pathogenesis. PMID- 22038540 TI - Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri. AB - Schwannomatosis is a rare hereditary cancer syndrome in which patients develop multiple non-vestibular schwannomas. The chromatin remodelling gene SMARCB1 (also known as INI1, hSNF5, and BAF47) has been identified as a schwannomatosis predisposing gene, being involved in a subset of sporadic and familial cases. Recent studies have shown that SMARCB1 may also be involved in the development of multiple meningiomas. Previously, we demonstrated that the SMARCB1 exon 2 missense mutation c.143 C > T segregates with the presence of meningiomas in five members of a large family with multiple meningiomas and schwannomas. We extended our genetic analyses by screening 44 additional at-risk family members and identified 13 new carriers. Eleven of these were subjected to magnetic resonance imaging (MRI) of brain and spine. In addition, we analyzed four meningiomas and two schwannomas from family members for the presence of schwannomatosis-specific changes. We found in each tumor retention of the SMARCB1 exon 2 mutation, acquisition of an independent neurofibromatosis type 2 (NF2) gene mutation, and loss of heterozygosity at SMARCB1 and NF2 by loss of the wild-type copy of both genes. The MRI scans revealed one or more falx meningiomas in seven of 11 (64%) newly identified SMARCB1 mutation carriers. We conclude that the SMARCB1 exon 2 missense mutation in this family predisposes to the development of meningiomas as well as schwannomas, occurring via the same genetic pathways, and that this mutation preferentially induces cranial meningiomas located at the falx cerebri. PMID- 22038538 TI - The function of alpha-2-adrenoceptors in the rat locus coeruleus is preserved in the chronic constriction injury model of neuropathic pain. AB - RATIONALE: Peripheral neuropathic pain is a chronic condition that may produce plastic changes in several brain regions. The noradrenergic locus coeruleus (LC) is a crucial component of ascending and descending pain pathways, both of which are frequently compromised after nerve injury. OBJECTIVES: The objective of the study was to examine whether chronic constriction injury (CCI), a model of neuropathic pain, alters noradrenergic activity in the rat LC. METHODS: Activity in the LC was assessed by electrophysiology and microdialysis, while protein expression was monitored in western blots and by immunohistochemistry. RESULTS: The pain threshold had dropped in injured rats 7 days after inducing neuropathy. While alpha-2-adrenoceptors mediate activity in the LC and in its terminal areas, no alterations in either spontaneous neuronal activity or extracellular noradrenaline levels were observed following CCI. Moreover, alpha-2-adrenoceptor activity in the LC of CCI rats remained unchanged after systemic administration of UK14,304, RX821002 or desipramine. Accordingly, extracellular noradrenaline levels in the LC were similar in CCI and control animals following local administration of clonidine or RX821002. In addition, there were no changes in the expression of the alpha-2-adrenoceptors, Galphai/z subunits or the regulators of G-protein signaling. However, pERK1/2 (phosphorylated extracellular signal regulated kinases 1/2) expression augmented in the spinal cord, paragigantocellularis nucleus (PGi) and dorsal raphe nucleus (DRN) following CCI. CONCLUSIONS: Neuropathic pain is not accompanied by modifications in tonic LC activity after the onset of pain. This may indicate that the signals from the PGi and DRN, the excitatory and inhibitory afferents of the LC, cancel one another out. PMID- 22038541 TI - The safety of fetal exposure to proton-pump inhibitors during pregnancy. AB - BACKGROUND: Proton-pump inhibitors (PPIs) are often needed in pregnancy due to the high rates of acid reflux. Previous studies did not include medical pregnancy terminations data, which may cause a bias toward the null hypothesis. We assessed the fetal safety of PPIs following exposure during gestation including data from medical pregnancy terminations. METHODS: A unified computerized database was created by linking a computerized database of medications dispensed from 1998 to 2009 to all women registered in "Clalit" HMO, southern district of Israel, with computerized databases containing maternal and infant hospitalization records from the district hospital. Rates of congenital malformations in PPIs exposed and unexposed pregnancies, as well as other adverse fetal effects were compared. Medical pregnancy termination data were included in the analysis. RESULTS: A total of 114,960 (75%) infants were born during the study period to women registered at "Clalit," 110,783 of them were singleton pregnancies; 1,239 women had medical pregnancy terminations, of which 468 were performed due to fetal malformations. A total of 1,186 infants and abortuses had been exposed to PPIs during the first trimester of pregnancy. Exposure to PPIs was not associated with an increased risk of congenital malformations (adjusted OR 1.06; 95% CI = 0.84 1.33). Similarly, exposure to PPIs during the third trimester of pregnancy was not associated with increased risk of perinatal mortality, premature delivery, low birth weight, or low Apgar scores. CONCLUSIONS: Intrauterine exposure to PPIs was not associated with increased risk for congenital malformations, perinatal mortality, or morbidity. These results are strengthened with the inclusion of data from medical pregnancy terminations. PMID- 22038542 TI - Gastrointestinal dysmotility. PMID- 22038543 TI - The evolution of infrahissian conduction time in myotonic dystrophy patients: clinical implications. AB - BACKGROUND: Myotonic dystrophy (MD1) is a hereditary autosomal dominant disease with variable penetrance. Cardiac conduction disturbances are frequent and may be responsible for sudden death, but its progression was heretofore unknown. AIMS: The aim of the study was to analyse the natural history of infrahissian conduction time in patients with a normal first electrophysiological test, and to identify the predictive value of the clinical and ECG factors accompanying an alteration of infrahissian conduction. METHODS: Among 127 consecutive screened MD patients, 25 were enrolled and underwent a second electrophysiological testing. The second electrophysiological test was carried out on patients showing new symptoms, new atrioventricular conduction disturbances on ECG, or significant modifications of signal-averaged (SA)-ECG, and on asymptomatic patients with a follow-up of at least 60 months since the first electrophysiological test. RESULTS: Among the 25 patients, four had new clinical symptoms, four others developed new atrioventricular conduction abnormalities on ECG and six had significant modifications of the SA-ECG. The mean His-ventricle (HV) interval increased significantly between the two electrophysiological studies (initial HV interval 52.1 ms+/-1.6 ms, final HV interval 61.4 ms+/-2.2 ms, p<0.005), with a mean increase of 1.2 ms/year. The five patients with HV interval of 70 ms or greater were implanted with a prophylactic dual-chamber pacemaker. Modifications of resting ECG and SA-ECG were strongly associated with HV interval prolongation. CONCLUSION: In patients with a normal initial electrophysiological study, modifications on the resting ECG and/or SA-ECG, on annual check-up, were associated with an alteration of infrahissian conduction. PMID- 22038544 TI - Use of cystatin C levels in estimating renal function and prognosis in patients with chronic systolic heart failure. AB - BACKGROUND: Estimates of glomerular filtration rate (GFR), including creatinine and creatinine based formulae, are inaccurate in extremes of GFR and substantially biased in patients with chronic heart failure (CHF). OBJECTIVE: To investigate whether serum cystatin C levels would be a better, more accurate and simple alternative for estimation of GFR and prognosis in CHF. DESIGN: Cohort study. SETTING: Chronic heart failure. PATIENTS, INTERVENTIONS AND MAIN OUTCOME MEASURE: In 102 CHF patients, the correlation between GFR as estimated by (125)I iothalamate clearance (GFR(IOTH)), the modification of diet in renal disease formula (GFR(MDRD)) and cystatin C was investigated. The combined endpoint consisted of the first occurrence of all cause mortality, heart transplantation or admission for CHF within 24 months. RESULTS: Mean age was 58+/-12 years; 77% were male. Mean left ventricular ejection fraction was 28+/-9%. Mean GFR(IOTH) was 75+/-27 ml/min/1.73 m(2), while median cystatin C levels were 0.80 (0.69 1.02) mg/l. GFR(IOTH) was strongly correlated with all renal function estimates, including 1/cystatin C (r=0.867, p<0.001). GFR(IOTH) was better predicted by 1/cystatin C compared to 1/serum creatinine (z=3.12, p=0.002), but equally predicted compared to GFR(MDRD) (z=0.92, p=0.356). Serum 1/cystatin C was a strong independent predictor of prognosis (HR: 2.27 per SD increase, 95% CI 1.12 to 4.63), comparable to GFR(MDRD). CONCLUSIONS: Cystatin C is an accurate and easy estimate of renal function with prognostic properties superior to serum creatinine and similar to creatinine based formulae in patients with CHF. PMID- 22038545 TI - Fas/FasL-mediated apoptosis and inflammation are key features of acute human spinal cord injury: implications for translational, clinical application. AB - The Fas/FasL system plays an important role in apoptosis, the inflammatory response and gliosis in a variety of neurologic disorders. A better understanding of these mechanisms could lead to effective therapeutic strategies following spinal cord injury (SCI). We explored these mechanisms by examining molecular changes in postmortem human spinal cord tissue from cases with acute and chronic SCI. Complementary studies were conducted using the in vivo FejotaTM clip compression model of SCI in Fas-deficient B6.MRL-Fas-lpr (lpr) and wild-type (Wt) mice to test Fas-mediated apoptosis, inflammation, gliosis and axonal degeneration by immunohistochemistry, Western blotting, gelatin zymography and ELISA with Mouse 32-plex cytokine/chemokine panel bead immunoassay. We report novel evidence that shows that Fas-mediated apoptosis of neurons and oligodendrocytes occurred in the injury epicenter in all cases of acute and subacute SCI and not in chronic SCI or in control cases. We also found significantly reduced apoptosis, expression of GFAP, NF-kappaB, p-IKappaB and iba1, increased number of CD4 positive T cells and MMP2 expression and reduced neurological dysfunction in lpr mice when compared with Wt mice after SCI. We found dramatically reduced inflammation and cytokines and chemokine expression in B6.MRL-Fas-lpr mice compared to Wt mice after SCI. In conclusion, we report multiple lines of evidence that Fas/FasL activation plays a pivotal role in mediating apoptosis, the inflammatory response and neurodegeneration after SCI, providing a compelling rationale for therapeutically targeting Fas in human SCI. PMID- 22038546 TI - Indigo biosynthesis by Comamonas sp. MQ. AB - An indigo-producing strain was isolated from activated sludge and identified as Comamonas sp. based on 16S rRNA analysis. It produced indigo at 26.5 mg/l with a conversion of indole to indigo of 47%. Indole at 50 mg/l plus 200 mg naphthalene/l gave 32.2 mg indigo/l with a 58% conversion. A pathway for indigo formation is proposed. This is the first study of indigo biosynthesis by Comamonas sp. PMID- 22038547 TI - Cloning, expression, and identification of a novel class IIa bacteriocin in the Escherichia coli cell-free protein expression system. AB - The NB-C1 gene, acquired from the result of data mining of the lactic acid bacteria genome, is a novel potential class IIa bacteriocin gene with the characteristic YGNGVxC cluster. To produce soluble NB-C1 efficiently and overcome issues of protein toxicity, we adopted a GFP fusion strategy using an Escherichia coli cell-free protein expression system. We constructed the expression vector pIVEX2.4d-GFP-NB-C1, which was expressed in both the batch mode and the continuous exchange cell-free (CECF) systems. The amount of soluble fusion protein achieved from the CECF system (2.2 mg/ml) was approximately three times higher than that in the batch mode (0.73 mg/ml). The soluble fusion protein was purified via one-step Ni-NTA affinity chromatography, with a concentration of 0.26 mg/ml and a purity of 95%. The purified NB-C1 showed strong antimicrobial activity against the indicator bacteria Listeria monocytogenes. PMID- 22038548 TI - Selection of Saccharomyces pastorianus variants with improved fermentation performance under very high gravity wort conditions. AB - Saccharomyces pastorianus FBY0095 was mutated and variants were selected for efficient very high gravity brewing using 15% (w/v) maltose and 15% (w/v) ethanol. Two useful variants were obtained of which one (L6) had growth, wort consumption and ethanol production rates of 0.036, 1.13 and 0.49 g l(-1) h(-1), respectively. The corresponding results for the wild type were 0.028, 0.98 and 0.4 g l(-1) h(-1), respectively. The vitality of the variant (expressed as acidification power) was 2.5 while that of the wild type was 2.3. There was also an obvious improvement on flavor of resulting beer when using L6 and the other variant. PMID- 22038549 TI - Polyarginine peptide IND-1 enhances recombinant human bone morphogenetic protein 2 yield in mammalian cells. AB - To improve recombinant human bone morphogenetic protein-2 (rhBMP-2) yield, cell lines stably expressing hBMP2 were cultured in the presence of polyarginine peptide IND-1 and showed up to 6-fold increase in the yield of mature BMP-2. Repeated addition of IND-1 to cell cultures consistently improved BMP-2 yields over 53 days without affecting cell growth and viability. Investigation of its mechanism of action showed that IND-1 inhibited pro-protein convertase (PC) activity when incubated with cell lysates. However, when intact cells were cultured with IND-1, no change in cellular PC activity was observed. Furthermore, knockdown of furin (a prototypical member of the PCs) in cells did not affect their BMP-2 yields, suggesting furin/PC inhibition is unlikely the mechanism by which IND-1 enhances BMP-2 yields. IND-1 as a medium additive thus enhances BMP-2 production in mammalian cell expression systems. PMID- 22038550 TI - Foam mitigation and exploitation in biosurfactant production. AB - Biosurfactants could potentially outperform traditional surfactants in many applications whilst being more sustainable to source, manufacture, use and dispose of. However, currently available fermentation production methods are too inefficient to manufacture biosurfactants for these high volume markets. Foaming in an inherent issue with biosurfactant production and adds significantly to the cost of production using traditional unit operations. This review illustrates how the application of process engineering has enabled nuisance foaming to be transformed into a cost saving feature of the production system. The scope of biosurfactants and their application is discussed and the fundamentals of foam generation and control are reviewed. The range of specific phenomena associated with the interaction of foams with bioproducts is assessed. Finally, recent work which has aimed at taking advantage of some of these phenomena in order to intensify the biosurfactant production process is discussed in detail. PMID- 22038551 TI - Recovery and purification of intracellular polyhydroxyalkanoates from recombinant Cupriavidus necator using water and ethanol. AB - A new halogen-free and environmental-friendly method using water and ethanol is developed as an alternative for the recovery of polyhydroxyalkanoates (PHA) from recombinant Cupriavidus necator in comparison to the established chloroform extraction method. After optimisation, our results showed that the halogen-free method produced a PHA with 81% purity and 96% recovery yield, in comparison to the chloroform extraction system which resulted in a highly pure PHA with 95% yield. Although the purity of the PHA using the new method is lower, the molecular weight of the extracted PHA is not compromised. This new method can be further developed as an alternative and more environmental-friendly method for industrial application. PMID- 22038552 TI - Association of gastric acid and mucus secretion level with low-dose aspirin induced gastropathy. AB - BACKGROUND: Low-dose aspirin is known to cause upper gastrointestinal complications. The mechanism by which the aspirin disrupts gastric mucosal integrity remains to be clarified. In this study we investigated the temporal association of gastric secretory parameters (acid and mucus) with aspirin-induced gastropathy. METHODS: In 42 long-term low-dose aspirin-takers and the same number of sex- and age-matched controls, pentagastrin-stimulated gastric juice was collected for 10 min during endoscopic examination. The collected gastric juice was divided and half was submitted to analysis for gastric acid (mEq/10 min) and the other half was analyzed for mucin (mg hexose/10 min) output. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score, and a score of more than 4 was defined as the presence of severe gastropathy. RESULTS: While gastric acid secretion did not differ significantly between aspirin-takers and controls, gastric mucus secretion, in terms of mucin output, was significantly increased in aspirin-takers compared to controls (4.1 (SD 4.8) vs. 2.3 (1.4) mg hexose/10 min, P < 0.05). Consequently, the acid/mucin ratio was significantly decreased in aspirin-takers compared to controls (1.2 (1.0) vs. 1.7 (1.4), P < 0.05). In the subanalysis of 25 aspirin-takers without severe gastropathy, gastric mucus secretion was increased and the acid/mucus ratio was decreased compared with controls, but there was no such association in the remaining 17 aspirin-takers with severe gastropathy. CONCLUSION: Overall, gastric mucus secretion is increased in aspirin-takers, suggesting a functional adaptive response to long-term administration of the drug. However, it is possible that the adaptive response is impaired in some aspirin takers, who might be susceptible to severe upper gastrointestinal complication. PMID- 22038553 TI - Impedance-pH reflux patterns can differentiate non-erosive reflux disease from functional heartburn patients. AB - INTRODUCTION: Symptom association is important to distinguish non-erosive reflux disease [NERD; abnormal oesophageal acid exposure time (AET) and/or positive symptom association] from functional heartburn (FH; normal AET and negative symptom association). Asymptomatic patients during reflux monitoring are challenging as symptom association cannot be assessed. AIM: To evaluate whether impedance-pH reflux patterns are useful to differentiate NERD from FH. METHODS: Endoscopy-negative reflux patients underwent impedance-pH off-therapy. Oesophageal AET, characteristics of reflux episodes and symptom association probability (SAP) were measured. Twenty patients asymptomatic during the first test repeated a second examination. RESULTS: Of 329 patients, 130 (40%) were pH POS, 120 (36%) pH-NEG/SAP+ (hypersensitive oesophagus = HO) and 79 (24%) pH NEG/SAP- (FH). Total and acid reflux episodes were significantly higher (p < 0.01) in pH-POS compared to pH-NEG/SAP+, pH-NEG/SAP- and healthy volunteers (HVs). Patients pH-NEG/SAP+ had a significantly increased number of weakly acidic reflux episodes compared to pH-POS, pH-NEG/SAP- and HVs (p < 0.01). The rate of proximal reflux episodes in pH-POS (50%) and pH-NEG/SAP+ (47%) was higher (p < 0.01) than in pH-NEG/SAP- (33%) and HVs (33%). Measuring AET, number of reflux episodes and percentage of proximal reflux events permits to identify FH in 70% of cases and HO in 80% of cases who repeated the examination. CONCLUSION: In patients with normal AET and SAP+, increased number of weakly acidic reflux and higher rate of proximal reflux are the main discriminant features. There is large overlap between FH and HVs. These differences can be of help in diagnosing patients with normal oesophageal acid exposure who fail to have symptoms during MII-pH testing. PMID- 22038554 TI - Geranylgeranylacetone has anti-hepatitis C virus activity via activation of mTOR in human hepatoma cells. AB - BACKGROUND: Geranylgeranylacetone (GGA), an isoprenoid compound which includes retinoids, has been used orally as an anti-ulcer drug in Japan. GGA acts as a potent inducer of anti-viral gene expression by stimulating ISGF3 formation in human hepatoma cells. This drug has few side effects and reinforces the effect of IFN when administered in combination with peg-IFN and ribavirin. This study verified the anti-HCV activity of GGA in a replicon system. In addition, mechanisms of anti-HCV activity were examined in the replicon cells. METHODS: OR6 cells stably harboring the full-length genotype 1 replicon containing the Renilla luciferase gene, ORN/C-5B/KE, were used to examine the influence of the anti-HCV effect of GGA. After treatment, the cells were harvested with Renilla lysis reagent and then subjected to a luciferase assay according to the manufacturer's protocol. RESULT: The results showed that GGA had anti-HCV activity. GGA induced anti-HCV replicon activity in a time- and dose-dependent manner. GGA did not activate the tyrosine 701 and serine 727 on STAT-1, and did not induce HSP-70 in OR6 cells. The anti-HCV effect depended on the GGA induced mTOR activity, not STAT-1 activity and PKR. An additive effect was observed with a combination of IFN and GGA. CONCLUSIONS: GGA has mTOR dependent anti-HCV activity. There is a possibility that the GGA anti-HCV activity can be complimented by IFN. It will be necessary to examine the clinical effectiveness of the combination of GGA and IFN for HCV patients in the future. PMID- 22038556 TI - Dendritic, nanosized building block for siloxane-based materials: a spherosilicate dendrimer. AB - A spherosilicate dendrimer (DMS-1) with closely spaced reaction sites (Si-H groups) on the dendrimer surface has been synthesized by stepwise silylation of double-four-ring silicate with chlorotriethoxysilane (ClSi(OEt)(3)) and subsequently with chlorodimethylsilane (ClSiHMe(2)). DMS-1 consists of a maximum of 40 Si atoms in the interior frameworks and 24 reactive Si-H groups on the surface. Because DMS-1 is spherical and about 1.5 nm in diameter, it can be regarded as the smallest well-defined silica-based nanoparticle. DMS-1 also forms molecular crystals and is soluble in typical organic solvents. A molecularly ordered silica-based hybrid can be prepared by heating a cast film of DMS-1 at 180 degrees C for 5 days. The surface of DMS-1 can be modified by hydrosilylation with 1-hexadecene, triethoxyvinylsilane, and allylic-terminated tetraethylene glycol monomethyl ether. More than 20 Si-H groups out of 24 react with these reagents. The solubilities of the products depend on the modification. DMS-1 is not only a building block for nanohybrids, but also the smallest and most precisely designed siloxane-based nanoparticle. PMID- 22038555 TI - The efficacy and safety of terlipressin and albumin in patients with type 1 hepatorenal syndrome: a multicenter, open-label, explorative study. AB - BACKGROUND: Treatment with terlipressin and albumin has been reported recently to be effective in improving renal function in the treatment of cirrhotic patients with hepatorenal syndrome (HRS). The aim of this prospective, multicenter study was to investigate the efficacy and safety of treatment with terlipressin and albumin in Japanese cirrhotic patients with type 1 HRS. METHODS: Eight cirrhotic patients with type 1 HRS were included in the study. Terlipressin (2.8 +/- 0.4 mg/day) and albumin (25.7 +/- 2.8 g/day) were given simultaneously for 6.3 +/- 4.2 days. RESULTS: Urine volume was significantly increased (p < 0.05) at the end of treatment compared with baseline. Serum creatinine levels were significantly decreased from 2.84 +/- 0.45 to 1.08 +/- 0.33 mg/dl (-61.9 +/- 9.9%, p < 0.05) after terlipressin and albumin administration. Creatinine clearance was significantly increased (p < 0.05) after treatment. Plasma renin activity and norepinephrine were significantly decreased (p < 0.05) after therapy. Six of the 8 patients (75%) showed a complete response (reduction of serum creatinine to 1.5 mg/dl or less). The cumulative probabilities of survival at 4 and 12 weeks were 63 and 13%, respectively. Complication of congestive heart failure possibly related to this regimen was seen in 1 patient, but ischemic adverse events were not observed during the treatment. CONCLUSIONS: Treatment with terlipressin and albumin improves renal function in cirrhotic patients with type 1 HRS. However, the survival of cirrhotic patients with type 1 HRS remains poor, although it may be improved by this specific therapy. PMID- 22038557 TI - Is Barthel Index a relevant measure for measuring prevalence of urinary incontinence in stroke patients? AB - AIMS: To compare the prevalence of urinary incontinence (UI) measured by Barthel Index and the Danish Prostate Symptom Score (DAN-PSS-1) questionnaire in stroke patients. METHODS: A cross-sectional, hospital based survey was initiated whereby 407 stroke patients, average age 67 (SD 12) years with a mean interval of 101 days since onset of last stroke at inclusion. The stroke patients self-reported the prevalence of UI by Barthel Index and the DAN-PSS-1 questionnaire. RESULTS: The prevalence of UI was 10.5% measured by the Barthel Index and 49% by the DAN PSS-1 questionnaire. Furthermore, the DAN-PSS-1 questionnaire distinguished between types of UI (38% urge UI, 28% stress UI, and 14% other UI). There were significantly fewer stroke patients who reported UI by the Barthel Index compared to the DAN-PSS questionnaire in term of urge UI (P < 0.001), stress UI (P < 0.001), and other UI (P < 0.001). CONCLUSIONS: The results showed that DAN-PSS-1 questionnaire contains more specific UI information compared to the Barthel Index. Fewer stroke patients reported UI by the Barthel Index compared to the DAN PSS-1 questionnaire and moreover the DAN-PSS-1 questionnaire enables identification of different UI-types. The Barthel Index is not sensitive to the UI prevalence; instead the authors suggest using a more specific instrument such as the DAN-PSS-1 questionnaire. PMID- 22038559 TI - Distress from voluntary refusal of food and fluids to hasten death: what is the role of continuous deep sedation? AB - In assisted dying, the end-of-life trajectory is shortened to relieve unbearable suffering. Unbearable suffering is defined broadly enough to include cognitive (early dementia), psychosocial or existential distress. It can include old-age afflictions that are neither life-threatening nor fatal in the "vulnerable elderly". The voluntary refusal of food and fluids (VRFF) combined with continuous deep sedation (CDS) for assisted dying is legal. Scientific understanding of awareness of internal and external nociceptive stimuli under CDS is rudimentary. CDS may blunt the wakefulness component of human consciousness without eradicating internal affective awareness of thirst and hunger. Patients may suffer because of the slow dying process following dehydration and starvation. The difficulty to adequately control distress, without bringing the dying process to a rapid conclusion by lethal pharmacological interventions, can cause feelings of guilt among hospice and medical staff. Furthermore, the double effect principle is not applicable in these situations because the primary objective of VRFF is to hasten death. Legal and societal debate should focus on sharpening the boundaries between assisted dying and palliative care. This separation is necessary to: 1) uphold trust in the patient-phyician relationship, and 2) preserve integrity and ethics of the medical profession. PMID- 22038560 TI - Elderly patients' and residents' perceptions of 'the good nurse': a literature review. AB - This article describes the findings of a mixed method literature review that examined the perceptions of elderly patients and residents of a good nurse in nursing homes, hospitals and home care. According to elderly patients and residents, good nurses are individuals who have the necessary technical and psychosocial skills to care for patients. They are at their disposal, promptly recognising the patients' needs. Good nurses like their job and are sincere and affectionate. They are understanding and caring. They do not hesitate to enter into a trust-based relationship with their patients. Knowing and understanding how elderly patients and nursing home residents perceive 'the good nurse' is crucial for providing quality care and for promoting better patient outcomes in geriatric care. PMID- 22038561 TI - Early in vivo changes in calcium ions, oxidative stress markers, and ion channel immunoreactivity following partial injury to the optic nerve. AB - CNS injury is often localized but can be followed by more widespread secondary degenerative events that usually result in greater functional loss. Using a partial transection model in rat optic nerve (ON). we recently demonstrated in vivo increases in the oxidative stress-associated enzyme MnSOD 5 min after injury. However, mechanisms by which early oxidative stress spreads remain unclear. In the present study, we assessed ion distributions, additional oxidative stress indicators, and ion channel immunoreactivity in ON in the first 24 hr after partial transection. Using nanoscale secondary ion mass spectroscopy (NanoSIMS), we demonstrate changes in the distribution pattern of Ca ions following partial ON transection. Regions of elevated Ca ions in normal ON in vivo rapidly decrease following partial ON transection, but there is an increasingly punctate distribution at 5 min and 24 hr after injury. We also show rapid decreases in catalase activity and later increases in immunoreactivity of the advanced glycation end product carboxymethyl lysine in astrocytes. Increased oxidative stress in astrocytes is accompanied by significantly increased immunoreactivity of the AMPA receptor subunit GluR1 and aquaporin 4 (AQP4). Taken together, the results indicate that Ca ion changes and oxidative stress are early events following partial ON injury that are associated with changes in GluR1 AMPA receptor subunits and altered ionic balance resulting from increased AQP4. PMID- 22038562 TI - The association of lipoprotein lipase PvuII polymorphism and niacin intake in the prevalence of metabolic syndrome: a KMSRI-Seoul study. AB - Lipoprotein lipase (LPL) polymorphism correlated with LPL activity is associated with plasma lipid and lipoprotein levels. We aimed to investigate the frequency of LPL PvuII polymorphism and effects of LPL PvuII polymorphism and niacin intake on the prevalence of metabolic syndrome (MetSyn) in Koreans. Lifestyle questionnaires, anthropometry, and dietary records were completed, and LPL PvuII polymorphism, LPL mass, and lipid profiles were determined in 548 Koreans (MetSyn: 278, Non-MetSyn: 270). The MetSyn group showed a significantly lower frequency of P1P1 (wild type) and a higher frequency of P1P2 (hetero type) than the non-MetSyn group. The P2P2 (mutant type) group significantly showed lower levels of HDLc and LPL mass and a higher level of TG than the P1P1 group. As niacin intake increased, LPL mass decreased in the P2P2 group (r (2) = 0.07). In particular, the lowest niacin intake group (<=14.82 mg/day) increased more than 3 times with regard to a higher risk of MetSyn than the others in the P2P2 mutant groups. However, the MetSyn risk declined 74% at the optimal levels of niacin intake (14.83-17.80 mg/day) in the P2P2 group compared to those of the P1 allele group. The findings indicate that optimal levels of niacin intake effectively decreased Korean MetSyn prevalence in the P2P2 mutant group. PMID- 22038563 TI - Large eddy simulation of mechanical mixing in anaerobic digesters. AB - A comprehensive study of anaerobic digestion requires an advanced turbulence model technique to accurately predict mixing flow patterns because the digestion process that involves mass transfer between anaerobes and their substrates is primarily dependent on detailed information about the fine structure of turbulence in the digesters. This study presents a large eddy simulation (LES) of mechanical agitation of non-Newtonian fluids in anaerobic digesters, in which the sliding mesh method is used to characterize the impeller rotation. The three subgrid scale (SGS) models investigated are: (i) Smagorinsky-Lilly model, (ii) wall-adapting local eddy-viscosity model, and (iii) kinetic energy transport (KET) model. The simulation results show that the three SGS models produce very similar flow fields. A comparison of the simulated and measured axial velocities indicates that the LES profile shapes are in general agreement with the experimental data but they differ markedly in velocity magnitudes. A check of impeller power and flow numbers demonstrates that all the SGS models give excellent predictions, with the KET model performing the best. Moreover, the performance of six Reynolds-averaged Navier-Stokes turbulence models are assessed and compared with the LES results. PMID- 22038564 TI - Genetic diagnosis of neuroacanthocytosis disorders using exome sequencing. AB - Neuroacanthocytoses are neurodegenerative disorders marked by phenotypic and genetic heterogeneity. There are several associated genetic loci, and many defects, including gene deletions and insertions, and missense, nonsense, and splicing mutations, have been found spread over hundreds of kilobases of genomic DNA. In some cases, specific diagnosis is unclear, particularly in the early stages of disease or when there is an atypical presentation. Determination of the precise genetic defect allows assignment of the diagnosis and permits carrier detection and genetic counseling. The objective of this report was to utilize exome sequencing for genetic diagnosis in the neuroacanthocytosis syndromes. Genomic DNA from 2 patients with clinical features of chorea-acanthocytosis was subjected to targeted exon capture. Captured DNA was subjected to ultrahigh throughput next-generation sequencing. Sequencing data were assembled, filtered against known human variant genetic databases, and results were analyzed. Both patients were compound heterozygotes for mutations in the VPS13A gene, the gene associated with chorea-acanthocytosis. Patient 1 had a 4-bp deletion that removes the 5' donor splice site of exon 58 and a nucleotide substitution that disrupts the 5' donor splice site of exon 70. Patient 2 had a dinucleotide deletion in exon 16 and a dinucleotide insertion in exon 33. No mutations were identified in the XK, PANK2, or JPH3 gene loci. Exome sequencing is a valuable diagnostic tool in the neuroacanthocytosis syndromes. These studies may provide a better understanding of the function of the associated proteins and provide insight into the pathogenesis of these disorders. PMID- 22038565 TI - Sources of education about breastfeeding and breast pump use: what effect do they have on breastfeeding duration? An analysis of the Infant Feeding Practices Survey II. AB - To examine the association between breastfeeding duration and sources of education about breastfeeding and breast pumps. We analyzed data from the Infant Feeding Practices Survey II (n = 2,586), a national longitudinal consumer-based study. We used chi(2) and ANOVA to contrast categorical and continuous variables, respectively, and logistic regression to model the association between breastfeeding duration and sources of education about breastfeeding and breast pump use. In unadjusted results, multiple sources of breastfeeding and breast pump education were significantly associated with breastfeeding duration. However, in multivariable logistic regression models, there was a negative association between longer breastfeeding duration and receiving breast pump education from a physician/physician assistant (OR 0.58, 95% CI 0.36-0.93); and a positive association between longer breastfeeding duration and receiving breastfeeding education from classes/support group (OR: 1.85, 95% CI: 1.24-2.76) and receiving breast pump education from friends/relatives (OR: 1.70, 95% CI: 1.13-2.55). Although healthcare providers such as physicians and nurses have regular contact with women, the only statistically significant association between breastfeeding and breast pump education from healthcare providers and longer breastfeeding duration was a negative one. This likely reflects time and resource limitations of clinical practice, but may also indicate a need for more consistent training for healthcare providers who provide breastfeeding and breast pump education. Social supports, such as education from classes/support groups and friends/relatives demonstrated positive associations with longer breastfeeding duration. This emphasizes the importance of fostering a positive sphere of influence around breastfeeding women. Future work should also investigate alternative levers of action, such as policies affecting insurance coverage of breast pumps. PMID- 22038566 TI - A comprehensive study of autonomic dysfunction in the fibromyalgia patients. AB - OBJECTIVES: The hypothesis of autonomic nervous system involvement in pathophysiology in the patients with fibromyalgia has been addressed and tested time and again but the existing reports are both contradictory and inconclusive. A complete knowledge of the degree of autonomic dysfunction in fibromyalgia patients would be more substantial. We conducted a comprehensive non-invasive study to investigate the complete autonomic profile of female patients with fibromyalgia. METHOD: An autonomic function test using a standard battery and heart rate variability analysis in the 42 fibromyalgia patients as well as 42 age matched healthy controls was performed. Both autonomic activity (tone) and reactivity were measured. Autonomic tone (both time and frequency domain parameters) was measured using heart rate variability (HRV) analysis. Autonomic reactivity was measured using a standard battery of autonomic function tests. RESULTS: Resting blood pressure (both systolic and diastolic) was significantly higher in the fibromyalgia patients than controls. The time domain variables and HF% as recorded by HRV were significantly lower in the patients than the controls. The autonomic reactivity for sympathetic and parasympathetic nervous system was found to be within normal limits. INTERPRETATION: The cardiac autonomic function is normal and the autonomic reflex arc seems to be intact in the patients with fibromyalgia. PMID- 22038567 TI - Mental health of Special Forces personnel deployed in battle. AB - PURPOSE: To compare the mental health problems of Special Forces with regular forces engaged in combat in the Sri Lanka Navy (SLN). METHODS: A population-based descriptive study was carried out to compare the mental health problems of Special Forces with regular forces in the Sri Lanka Navy (SLN) deployed in combat areas for at least 1 year. Participants were selected by simple random sampling. The outcome measures were common mental disorder measured using the General Health Questionnaire, PTSD, fatigue, multiple physical symptoms and hazardous alcohol use. RESULTS: Overall exposure to potentially traumatic events was high in both groups, with Special Forces experiencing significantly more traumatic events. More than 80% of the Special Forces had experiences of discharging weapons in direct combat, engaging in combat with enemy vessels and seeing the dead or wounded. Special Forces had significantly less common mental disorders, fatigue and fair or poor general health than regular forces. Fair or poor general health (21.1%) and fatigue (18.4%) were the commonest problems in the regular forces. Hazardous drinking was the commonest mental health problem among the Special Forces (17%). Prevalence of PTSD was 1.9% in the Special Forces and 2.9% among the regular forces. Exposure to traumatic events and problems with family life were identified as risk factors. CONCLUSIONS: Elite troops suffered less negative mental health consequences than regular forces despite higher combat exposure. Comradeship and unit cohesion protected Special Forces from negative mental health outcome of combat. PMID- 22038569 TI - Integrated continuous flow polymerase chain reaction and micro-capillary electrophoresis system with bioaffinity preconcentration. AB - An integrated and modular DNA analysis system is reported that consists of two modules: (i) A continuous flow polymerase chain reaction (CFPCR) module fabricated in a high T(g) (150 degrees C) polycarbonate substrate in which selected gene fragments were amplified using biotin and fluorescently labeled primers accomplished by continuously shuttling small packets of PCR reagents and template through isothermal zones as opposed to heating and cooling large thermal masses typically performed in batch-type thermal reactors. (ii) MUCE (micro capillary electrophoresis) module fabricated in poly(methylmethacrylate) (PMMA), which utilized a bioaffinity selection and purification bed (2.9 MUL) to preconcentrate and purify the PCR products generated from the CFPCR module prior to electrophoretic sorting. Biotin-labeled CFPCR products were hydrostatically pumped through the streptavidin-modified bed, where they were extracted onto the surface of micropillars. The affinity bed was also fabricated in PMMA and was populated with an array of microposts (50 MUm width; 100 MUm height) yielding a total surface area of ~117 mm(2). This solid-phase extraction (SPE) process demonstrated high selectivity for biotinylated amplicons and utilized the strong streptavidin/biotin interaction (K(d) = 10(-15) M) to generate high recoveries. The SPE selected CFPCR products were thermally denatured and single-stranded DNA released for injection into a 7-cm-long MUCE channel for size-based separations and fluorescence detection. The utility of the system was demonstrated using Alu DNA typing for gender and ethnicity determinations as a model. Compared with the traditional cross-T injection procedure typically used for MUCE, the affinity pre concentration and injection procedure generated signal enhancements of 17- to 40 fold, critical for CFPCR thermal cyclers due to Taylor dispersion associated with their operation. PMID- 22038568 TI - Impact of pre-enlistment antisocial behaviour on behavioural outcomes among U.K. military personnel. AB - PURPOSE: Concern has been raised over alleged increases in antisocial behaviour by military personnel returning from the deployment in Iraq and Afghanistan. U.S. based research has shown that post-deployment violence is related not only to combat experience, but also to pre-enlistment antisocial behaviour (ASB). This study aimed to examine the association between pre-enlistment ASB and later behavioural outcomes, including aggression, in a large randomly selected U.K. military cohort. METHODS: Baseline data from a cohort study of 10,272 U.K. military personnel in service at the time of the Iraq war in 2003 were analysed. The associations between pre-enlistment ASB and a range of socio-demographic and military variables were examined as potential confounders. Logistic regression analyses were performed to examine the relationship between pre-enlistment ASB and military behavioural outcomes such as severe alcohol use, violence/aggression and risk-taking behaviour, controlling for confounders. RESULTS: 18.1% were defined as having displayed pre-enlistment ASB. Pre-enlistment ASB was significantly associated with factors such as younger age, low educational achievement, male gender, non-officer rank, Army personnel, being a regular, increasing time spent on the deployment and having a combat role. Pre-enlistment ASB was associated with increased risk of negative behavioural outcomes (severe alcohol misuse, outbursts of anger or irritability, fighting or assaultative behaviour and risk-taking behaviour), after controlling for confounders, suggesting that such background information may identify individuals who are more vulnerable to subsequent behavioural disturbance. CONCLUSION: The results of this study suggest that those already demonstrating ASB prior to joining the military are more likely to continue on this trajectory, thus emphasising the importance of considering pre-enlistment behaviour when exploring the aetiology of aggression in military personnel. PMID- 22038570 TI - Evaluation of biological effects of nanomaterials. Part I. Cyto- and genotoxicity of nanosilver composites applied in textile technologies. AB - OBJECTIVES: The aim of this study was to investigate the cyto- and genotoxicity of nanocomposites (NCs) and generation of reactive oxygen species (ROS) as a result of particle-cell interactions. MATERIALS AND METHODS: Titanium dioxide (TiO(2)-Ag) and ion-exchange resin (Res-Ag), both coated with silver (Ag), were examined. The murine macrophage J774A.1 cells were incubated in vitro with NC at different concentrations for 24 h. Cytotoxicity was analyzed by the methylthiazolyldiphenyl-tetrazolium bromide reduction test (MTT reduction test). ROS generation was assessed by incubation of cells with dichlorodihydrofluorescein diacetate (DCF) and flow cytometry. DNA damage was detected by comet assay and included single-strand breaks (SSB), alkali-labile sites (ALS) and oxidative DNA damage after formamidopyrimidine glycosylase (FPG) treatment. The tail moment was used as an indicator of DNA damage. RESULTS: TiO(2)-Ag was not cytotoxic up to 200 MUg/ml, whereas IC(50) for Res-Ag was found to be 23 MUg/ml. Intracellular ROS levels were elevated after 4 h of exposure to Res-Ag at the concentration of 50 MUg/ml. Both types of NC induced fragmentation of DNA strands, but only one of the composites caused damage to purine bases. TiO(2)-Ag induced SSB of DNA at concentrations of 10 and 5 MUg/ml. For Res-Ag, a concentration-dependent increase in tail moments was observed. CONCLUSIONS: Silver-coated nanocomposites (both TiO(2)-Ag and Res-Ag) may cause genotoxic effects in murine macrophages J774A.1. Res-Ag increased generation of ROS which suggested that toxicity of Res-Ag in murine macrophages is likely to be mediated through oxidative stress. This paper will support industry and regulators alike in the assessment of hazards and risks and methods for their mitigation at the earliest possible stage in material and product development. PMID- 22038571 TI - Does exercise improve weight loss after bariatric surgery? A systematic review. AB - Bariatric surgery leads to significant weight loss in the obese patient. Exercise has been shown to improve weight loss and body composition in non-surgical weight loss programmes. The role of exercise to improve weight loss following bariatric surgery is unclear. The objective of this review is to systematically appraise the evidence regarding exercise for weight loss in the treatment of obesity in bariatric surgery patients. MEDLINE, AMED, CINAHL, EBM Reviews (Cochrane Database, Cochrane Clinical Trials Register) were searched, obesity-related journals were hand-searched and reference lists checked. Studies containing post surgical patients and exercise were included with the primary outcome of interest being weight loss. A literature search identified 17 publications exploring exercise in bariatric surgery patients. All studies were observational; there were no intervention studies found. The most commonly used instruments to measure activity level were questionnaires followed by telephone interview, surgeon reporting and clinical notes. There was a positive relationship between increased exercise and weight loss after surgery in 15 studies. Meta-analysis demonstrated in patients participating in exercise a standardised mean of 3.62 kg (CI = 1.28, 5.96) greater weight loss compared to the minimal exercise groups. Observational studies suggest that exercise is associated with greater weight loss following bariatric surgery. Randomised controlled trials are required to further examine this relationship. PMID- 22038572 TI - Only C-reactive protein, but not TNF-alpha or IL6, reflects the improvement in inflammation after bariatric surgery. AB - BACKGROUND: Increased C-reactive protein (CRP) levels strongly predict inflammatory diseases such as obesity and tissue damage. We wanted to study the CRP in plasma and tissue in morbidly obese patients before and after surgery and relate it with the expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in tissues. METHODS: We analyzed CRP concentration in plasma, adipose and liver, and the expression of IL-6 and TNF-alpha, in those tissues, in 34 morbidly obese patients before and 1, 6 and 12 months after gastric bypass. RESULTS: Morbidly obese had a greater amount of CRP in plasma (3 times) and tissues (21, 5 and 7 times more in liver, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), respectively) than control subjects. The expression of IL-6 in SAT showed a similar profile to plasma and SAT CRP in both obese patients and after weight loss, despite no significant correlation was found. We were only able to detect IL-6 in the liver of a subset of patients. The expression of TNF-alpha after surgery showed a no significant slight tendency to decrease in SAT with weight loss, but in the liver, we did not observe any change. CONCLUSION: IL-6 in SAT, but not in liver, seems to be more closely related to plasma and tissue CRP than TNF-alpha in both obese patients and after weight loss. Plasma CRP protein perfectly reflects the decrease in inflammation and improves with weight loss in the tissues. PMID- 22038573 TI - Chemical phenotypes of P2X2 purinoreceptor immunoreactive cell bodies in the area postrema. AB - Purines such as adenosine 5'-triphosphate (ATP) act as extracellular messengers through specific purinergic receptors. Three different classes of purinergic receptors have been identified and termed P1, P2X, and P2Y. The purinergic receptor subunit P2X2 is a ligand-gated ion channel that is widely expressed by neurons in the CNS. In the brainstem medulla oblongata, the ionotropic P2X2 receptor (P2X2R) is enriched in the area postrema (AP). Two different antisera to P2X2R were used to determine the chemical nature of P2X2R immunoreactive cell bodies in the rat AP, an area lacking a blood-brain barrier. Subcellularly, P2X2R immunoreactivity was located to the periphery of individual cell bodies. The majority of P2X2R-immunoreactive cells were shown to contain tyrosine hydroxylase (TH) (63.5 +/- 7.7%) and dopamine beta-hydroxylase (61.5 +/- 5.1%). Phenylethanolamine N-methyltransferase (PNMT)-containing cells were not detected in the AP, supporting a noradrenergic nature of P2X2R cells in the AP. There were no P2X2R-immunoreactive cells in the AP that contained the GABA-synthesizing enzyme glutamic acid decarboxylase 65. Only single vesicular glutamate transporter 2-immunoreactive cell bodies that were not P2X2R-positive were demonstrated in the AP. Some P2X2R-positive cells in the AP were immunoreactive for the neuropeptides substance P and pituitary adenylate cyclase-activating polypeptide, whereas dynorphin-, enkephalin-, or cholecystokinin-positive cells were not P2X2R-immunoreactive. Presence of P2X2R in a majority of noradrenergic cells of the AP implies that ATP may have a regulatory action on neuronal noradrenaline release from the AP, a circumventricular organ with a strategic position enabling interactions between circulating substances and the central nervous system. PMID- 22038574 TI - The impact of commercially available purinergic ligands on purinergic signalling research. AB - Due to the extremely wide-spread expression of purinergic receptors, purinergic signalling has been implicated in numerous physiological and pathophysiological areas. To better understand the involvement of purinergic receptors in such areas, the researcher's requirement for diverse and varied purinergic receptor ligands has greatly increased. This has generated increased commercial opportunities for life science suppliers, and ultimately, has led to a rapid expansion in the number of commercially available purinergic receptor ligands. The wide-spread availability of ligands to researchers has greatly benefited the scientific community, nurturing the rapid and continued expansion of the purinergic signalling field. PMID- 22038575 TI - Electroretinogram findings in unilateral optic neuritis. AB - To report the electrophysiological findings in patients with unilateral optic neuritis (ON), with particular reference to the electroretinogram (ERG). A retrospective analysis of full-field ERG, pattern ERG (PERG) and pattern visual evoked potential findings from 46 patients with clinical and electrophysiological findings in keeping with unilateral ON. ISCEV standard ERGs did not significantly differ between the optic neuritis and fellow eyes, nor between patients with and without MS. Differences were present in the N95 component of the PERG, which was significantly lower in the affected eye, and the pattern reversal visual evoked potential, which showed significantly longer peak time (latency) in the affected eye. In addition, there was a significant difference between patients with and without multiple sclerosis (MS). No significant inter-ocular asymmetry in ISCEV standard ERGs was present in these cases of unilateral optic neuritis, either as a clinically isolated syndrome or as part of multiple sclerosis. All ERGs recorded were normal. PMID- 22038576 TI - ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). AB - The clinical multifocal electroretinogram (mfERG) is an electrophysiological test of local retinal function. With this technique, many local ERG responses are recorded quasi-simultaneously from the cone-driven retina under light-adapted conditions. This document, from the International Society for Clinical Electrophysiology of Vision (ISCEV: www.iscev.org ), replaces the ISCEV guidelines for the mfERG published in 2007. Standards for performance of the basic clinical mfERG test with a stimulus array of 61 or 103 hexagons, as well as for reporting the results, are specified. PMID- 22038577 TI - Haloperidol dosing strategies in the treatment of delirium in the critically ill. AB - Delirium is the most common mental disturbance in critically-ill patients and results in significant morbidity and mortality. Haloperidol is a preferred agent for the treatment of delirium in this population because of its rapid onset of action and lack of hemodynamic effects. Despite its widespread use in the critical care setting, most of the relevant data are obtained from case series or extrapolated from non-critically-ill populations. This review provides an overview of haloperidol pharmacokinetics and a comprehensive summary of the evidence for various haloperidol dosing regimens in the treatment of delirium in critically-ill patients. A comprehensive literature search was conducted in Medline, Embase, and International Pharmaceutical Abstracts with "haloperidol", "delirium", "agitation", "critically-ill", and "intensive care" as keywords. Studies involving haloperidol for delirium prophylaxis, non-critical care settings, and terminally-ill subjects were excluded. Eleven studies were identified: four with intermittent IV haloperidol, four with continuous IV infusion haloperidol, two with oral/enteral haloperidol, and one with IM haloperidol. All of the case reports, case series, and descriptive studies have shown a benefit with haloperidol, but publication bias is likely present. Only three studies were controlled studies, but all had small sample sizes and methodological flaws. Randomized, double-blind, active-comparator trials of haloperidol with allocation concealment are needed. Subsequent research should focus on using validated delirium screening and assessment scales for more objective identification and measurement of delirium outcomes. PMID- 22038578 TI - Fever control in the NICU: is there still a simpler and cheaper solution? PMID- 22038579 TI - Systematic review and meta-analysis of the use of lightweight versus heavyweight mesh in open inguinal hernia repair. AB - BACKGROUND: The objective of this study was systematically to analyse published randomized trials comparing lightweight mesh (LWM) with heavyweight mesh (HWM) in open inguinal hernia repair. METHODS: Randomized trials on LWM versus HWM were selected from the standard electronic databases. Reported outcomes were analysed systematically using RevMan. Pooled risk ratios were calculated for categorical outcomes, and mean differences for secondary continuous outcomes, using the fixed effects and random-effects models for meta-analysis. RESULTS: Nine randomized trials containing 2310 patients were included. There was significant heterogeneity among trials. There was no difference in duration of operation, postoperative pain, recurrence rate, testicular atrophy and time to return to work between LWM and HWM groups. The two mesh types had a similar risk of perioperative complications, but LWM was associated with a reduced risk of developing chronic groin pain (risk ratio (RR) 0.61, 95 per cent confidence interval 0.50 to 0.74) and a reduced risk of developing other groin symptoms, such as stiffness and foreign body sensations (RR 0.64, 0.50 to 0.81). CONCLUSION: The use of LWM for open inguinal hernia repair was not associated with an increased risk of hernia recurrence. LWM reduced the incidence of chronic groin pain as well as the risk of developing other groin symptoms. PMID- 22038580 TI - Nanoparticles in aquatic systems. AB - Nanoparticles (NP) are ubiquitous in environmental and technical aquatic systems. Understanding the role and the fate of NP in these systems is an interdisciplinary challenge requiring innovative experimental, theoretical and analytical approaches and critical reflection of classical concepts. This contribution critically reviews the outstanding properties of NP and the resulting consequences for their behaviour in environmental and technical aquatic systems considering natural NP which are mostly geogenic or biogeogenic, and engineered NP. Owing to the severe lack of data on the occurrence of NP in environmental aquatic systems, it is a key task of researchers to further develop analytical methods for the sensitive detection of NP directly in aqueous samples. There is urgent need for standardisation of analytical methods for detection and characterisation of NP, and for toxicity tests to assess possible adverse effects of NP. In this context, NP reference materials have to be defined as a common fundament for research in this field. PMID- 22038581 TI - Ambient aerosols and human health: working towards a combined analytical and toxicological approach. PMID- 22038582 TI - Purge and trap with monolithic sorbent for gas chromatographic analysis of pesticides in honey. AB - Polydivinylbenzene (P-DVB) and silica monolithic materials were synthesised in capillaries and then used to adsorb nine organonitrogen pesticides extracted from honey. After adsorption, each monolith-capillary was connected to a gas chromatograph (GC) with nitrogen-phosphorous detector (NPD). The silica monolith gave better peak shape and intensity than the P-DVB monolith. Formulation of silica monolith with tetramethoxysilane (TMOS) as a sole initiator provided better separation and higher peak intensity, compared to those with methyltrimethoxysilane (MTMS) and (3:1) TMOS/MTMS initiators. The optimum internal diameter and length of silica monolith-capillary were 0.25 mm and 5 cm, respectively. The purge and trap conditions were optimised by purging with nitrogen and heating the honey sample solution at 100 degrees C for 60 min. Recovery of the method was in a range of 84.95-99.71% and the detection limits of the pesticides determined by using GC-NPD and GC-mass spectrometric detector (MSD) ranged between 0.36-1.75 and 0.13-0.25 ng g(-1), respectively. PMID- 22038583 TI - Phosphorylation site localization in peptides by MALDI MS/MS and the Mascot Delta Score. AB - Owing to its broad biological significance, the large-scale analysis of protein phosphorylation is more and more getting into the focus of proteomic research. Thousands of phosphopeptides can nowadays be identified using state-of-the-art tandem mass spectrometers in conjunction with sequence database searching, but localizing the phosphate group to a particular amino acid in the peptide sequence is often still difficult. Using 180 individually synthesized phosphopeptides with precisely known phosphorylation sites (p-sites), we have assessed the merits of the Mascot Delta Score (MD score) for the assignment of phosphorylation sites from tandem mass spectra (MS/MS) generated on four different matrix-assisted laser desorption ionization (MALDI) mass spectrometers including tandem time-of flight (TOF/TOF), quadrupole time-of-flight, and ion trap mass analyzers. The results show that phosphorylation site identification is generally possible with false localization rates of about 10%. However, a comparison to previous work also revealed that phosphorylation site determination by MALDI MS/MS is less accurate than by ESI-MS/MS particularly if several and/or adjacent possible phosphorylation acceptor sites exist in a peptide sequence. We are making the tandem MS spectra and phosphopeptide collection available to the community so that scientists may adapt the MD scores reported here to their analytical environment and so that informatics developers may integrate the MD score into proteomic data analysis pipelines. PMID- 22038584 TI - Flow injection analysis of volatile phenols in environmental water samples using CdTe/ZnSe nanocrystals as a fluorescent probe. AB - On the basis of flow injection analysis technology, a simple, accurate, and sensitive method has been developed for the determination of volatile phenols in environmental water samples by using CdTe/ZnSe nanocrystals as a fluorescent probe. The influences of coexisting metal ions and volatile phenol substitutes were also investigated. The method developed for analysis of volatile phenols displayed very good linearity in the range from 1.0 * 10(-8) to 4.0 * 10(-7) g L( 1), with a correlation coefficient greater than 0.995 and a detection limit down to 2.7 * 10(-9) g L(-1) (signal-to-noise ratio 3). The proposed method was successfully applied to determine the content of volatile phenols in environmental water samples, and the quantitative recoveries were 93.4-106.1%. A possible reaction mechanism for the quenching of fluorescence is discussed using UV-vis absorption spectra, fluorescence spectra, and time-resolved luminescence spectra of volatile phenols obtained by titrating a CdTe/ZnSe nanocrystal aqueous solution and zeta potential data. PMID- 22038585 TI - A CMOS image sensor to recognize the cardiovascular disease markers troponin I and C-reactive protein. AB - A complementary metal oxide semiconductor (CMOS) image sensor was utilized to detect the interaction of cardiovascular disease markers, troponin I and C reactive protein. Each marker with its respective antibodies was adsorbed to an indium nanoparticle (InNP)-coated glass substrate. Dielectric layers of antigens and antibodies bound onto and interacted on conducting InNPs. Normal room light passed through these protein-layer-bound substrates and hit the CMOS image sensor surface, and the number of photons was detected and converted into digital form. We tested this approach for real-time monitoring of cardiac disease markers based on photon count, demonstrating its low cost and its capacity to detect antigens with high sensitivity at picogram per milliliter concentration. PMID- 22038586 TI - Forensic analysis of Salvia divinorum using multivariate statistical procedures. Part I: discrimination from related Salvia species. AB - Salvia divinorum is a hallucinogenic herb that is internationally regulated. In this study, salvinorin A, the active compound in S. divinorum, was extracted from S. divinorum plant leaves using a 5-min extraction with dichloromethane. Four additional Salvia species (Salvia officinalis, Salvia guaranitica, Salvia splendens, and Salvia nemorosa) were extracted using this procedure, and all extracts were analyzed by gas chromatography-mass spectrometry. Differentiation of S. divinorum from other Salvia species was successful based on visual assessment of the resulting chromatograms. To provide a more objective comparison, the total ion chromatograms (TICs) were subjected to principal components analysis (PCA). Prior to PCA, the TICs were subjected to a series of data pretreatment procedures to minimize non-chemical sources of variance in the data set. Successful discrimination of S. divinorum from the other four Salvia species was possible based on visual assessment of the PCA scores plot. To provide a numerical assessment of the discrimination, a series of statistical procedures such as Euclidean distance measurement, hierarchical cluster analysis, Student's t tests, Wilcoxon rank-sum tests, and Pearson product moment correlation were also applied to the PCA scores. The statistical procedures were then compared to determine the advantages and disadvantages for forensic applications. PMID- 22038587 TI - Synchrotron radiation Fourier-transform infrared and Raman microspectroscopy study showing an increased frequency of creatine inclusions in the rat hippocampal formation following pilocarpine-induced seizures. AB - In the present work, synchrotron radiation Fourier-transform infrared (SRFTIR) and Raman microspectroscopies were used to evaluate a possible role of creatine in the pathogenesis and progress of pilocarpine-evoked seizures and seizure induced neurodegenerative changes in the rat hippocampal tissue. The main goal of this study was to identify creatine deposits within the examined brain area, to analyze their frequency in epileptic animals and naive controls and to examine correlations between the number of inclusions in the hippocampal formation of epileptic rats and the quantitative parameters describing animal behavior during 6-h observation period after pilocarpine injection. The presence of creatine in the brain tissue was confirmed based on the vibrational bands specific for this compound in the infrared and Raman spectra. These were the bands occurring at the wavenumbers around 2800, 1621, 1398, and 1304 cm(-1) in IR spectra and around 1056, 908 and 834 cm(-1) in the Raman spectra. Creatine was detected in eight of ten analyzed epileptic samples and in only one of six controls under the study. The number of deposits in epileptic animals varied from 1 to 100 and a relative majority of inclusions were detected in the area of the Dentate Gyrus and in the multiform hippocampal layer. Moreover, the number of creatine inclusions was positively correlated with the total time of seizure activity. PMID- 22038588 TI - Quantitative determination of taurine and related biomarkers in urine by liquid chromatography-tandem mass spectrometry. AB - Current urinary bladder cancer diagnosis is commonly based on a biopsy obtained during cystoscopy. This invasive method causes discomfort and pain in patients. Recently, taurine and several other compounds such as L-phenylalanine and hippuric acid in urine were found to be indicators of bladder cancer. However, because of a lack of sensitive and accurate analytical techniques, it is impossible to detect these compounds in urine at low levels. In this study, using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a noninvasive method was developed to separate and detect these compounds in urine. (15)N(2)-L glutamine was used as the internal standard, and creatinine acted as an indicator for urine dilution. A phenyl-hexyl column was used for the separation at an isocratic condition of 0.2% formic acid in water and 0.2% formic acid in methanol. Analytes were detected in multiple-reaction monitoring with positive ionization mode. The limit of detection range is 0.18-6 nM and the limit of quantitation ranges from 0.6 to 17.6 nM. The parameters affecting separation and quantification were also investigated and optimized. Proper clinical validation of these biomarkers can be done using this reliable, fast, and simple method. Furthermore, with simple modifications, this method could be applied to other physiological fluids and other types of diseases. PMID- 22038589 TI - The aromatic peroxygenase from Marasmius rutola--a new enzyme for biosensor applications. AB - The aromatic peroxygenase (APO; EC 1.11.2.1) from the agraric basidomycete Marasmius rotula (MroAPO) immobilized at the chitosan-capped gold-nanoparticle modified glassy carbon electrode displayed a pair of redox peaks with a midpoint potential of -278.5 mV vs. AgCl/AgCl (1 M KCl) for the Fe(2+)/Fe(3+) redox couple of the heme-thiolate-containing protein. MroAPO oxidizes aromatic substrates such as aniline, p-aminophenol, hydroquinone, resorcinol, catechol, and paracetamol by means of hydrogen peroxide. The substrate spectrum overlaps with those of cytochrome P450s and plant peroxidases which are relevant in environmental analysis and drug monitoring. In M. rotula peroxygenase-based enzyme electrodes, the signal is generated by the reduction of electrode-active reaction products (e.g., p-benzoquinone and p-quinoneimine) with electro-enzymatic recycling of the analyte. In these enzyme electrodes, the signal reflects the conversion of all substrates thus representing an overall parameter in complex media. The performance of these sensors and their further development are discussed. PMID- 22038590 TI - Tunable fragmentation of organic molecules in laser ablation glow discharge time of-flight mass spectrometry. AB - A DC-pulsed glow discharge (GD) has distinct temporal regimes which are characterized by "softer" or "harder" ionization of analytes introduced into the discharge. It is thus possible to obtain both molecular weight and structural fragment information from the same spectra. In order to extend the capabilities of this technique a laser ablation (LA) sampling system was coupled to a DC pulsed GD and to a time-of-flight (TOF) mass spectrometer (MS) for characterizing organic samples such as oleic acid, reserpine, two different peptides, and a polymer. Both hard and soft ionization regimes were studied. These LAGD-TOFMS results were compared to matrix-assisted laser desorption ionization (MALDI) spectra using the same compounds (i.e., analytes, concentration, and matrix). It was found that LAGD offers tunable ionization and provides a reduced matrix dependence. However, the sensitivity achieved by the prototype LAGD-TOFMS was significantly lower when compared with commercially available MALDI-TOFMS instrumentation. Since LAGD-TOFMS is rather new, some technical details to increase its sensitivity are discussed. PMID- 22038591 TI - Dual-polarization interferometry for quantification of small molecules using aptamers. AB - An interferometry-based method was developed for detection of a small molecule, argininamide. The quantification of argininamide was demonstrated using aptamers immobilized on silicone oxynitride sensor surface via avidin-biotin binding. The aptamers formed a thin film over avidin layer corresponding to a thickness of 1.2 nm, consistent with a molecular positioning of multipoint attachment to the surface. The binding of argininamide did not cause any significant changes in the thickness of the aptamer film, suggesting that the specific binding did not affect the overall conformation of the aptamer molecules after adaptive rearrangement of aptamer molecules. However, the binding results in clearly detectable changes in mass calculated from multiple parameters determined by mass deposition and structural changes. The limit of detection of the developed sensor was determined to be 5 MUM. The sensor can monitor real-time changes in argininamide concentrations with high reliability and sensitivity. The model system demonstrated that a combined measurement considering structural and mass changes through interferometry-based techniques can overcome one of the major problems associated with real-time monitoring of small mass analytes. PMID- 22038592 TI - Preparing a metal-ion chelated immobilized enzyme reactor based on the polyacrylamide monolith grafted with polyethylenimine for a facile regeneration and high throughput tryptic digestion in proteomics. AB - Initially, a poly (glycidyl methacrylate-co-acrylamide-co-methylenebisacrylamide) monolith was prepared in the 100 MUm i.d. capillary, and then was grafted with polyethylenimine (Mw, ~25,000) for adsorbing Cu(2+), followed by chelating trypsin. As a result, efficient digestion for BSA (100 ng/MUL) was completed within 50 s via such immobilized enzyme reactor (IMER); yielding 47% sequence coverage by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. Compared with the conventional method for preparing the metal-ion chelated IMER, the regeneration of such IMER can be achieved facilely by the respective 30 min desorption and re-adsorption of trypsin, and 51% sequence coverage was obtained for 50 s BSA digestion after regeneration. BSA down to femtomole was also efficiently digested by the prepared regenerable IMER. Meanwhile, after the consecutive digestion of myoglobin and BSA, there was not any mutual interference for both during MALDI-TOF MS identification, indicating the low nonspecific adsorption of such regenerable IMER. To test the applicability of regenerable IMER for complex sample profiling, proteins (150 ng) extracted from Escherichia coli were digested within 80 s by the regenerable IMER and further analyzed by nanoreversed phase liquid chromatography-electrospray ionization-mass spectrometry successfully, showing its practicability for the high throughput analysis of complex samples. PMID- 22038593 TI - Hypomethylation of the thymosin beta(10) gene is not associated with its overexpression in non-small cell lung cancer. AB - Lung cancer is the leading cause of cancer-related deaths worldwide and is usually associated with a late diagnosis and a poor prognosis. Thymosin beta(10) (TMSB10) is a monomeric actin sequestering protein that regulates actin cytoskeleton organization. The aberrant TMSB10 expression has been implicated in the pathogenesis of human cancers. However, its role in carcinogenesis is still controversial. To better understand the role of TMSB10 in lung tumorigenesis and its regulatory mechanism, we examined the methylation status and expression of the TMSB10 gene in non-small cell lung cancers (NSCLCs) using methylation specific PCR (MSP) and immunohistochemistry (IHC), respectively. MSP analysis showed that the TMSB10 promoter was already unmethylated in most tumor tissues and became demethylated in 20 (14.4%) of the 139 NSCLCs. TMSB10 hypomethylation was not significantly correlated with the clinicopathological features. IHC showed that the TMSB10 protein was strongly expressed in the cytoplasm of malignant cells and its overexpression was detected in 50.0% of the tumor tissues compared to normal tissues. TMSB10 overexpression was frequently observed in sqaumous cell carcinomas compared to adenocarcinomas with border line significance (P = 0.072). However, TMSB10 methylation status was not linked to its overexpression. Collectively, these results suggest that TMSB10 hypomethylation may be a frequent event in NSCLCs, but it may not be a common mechanism underlying TMSB10 overexpression. However, further studies with large numbers of patients are needed to confirm our findings. PMID- 22038594 TI - Novel GFP expression using a short N-terminal polypeptide through the defined twin-arginine translocation (Tat) pathway. AB - Escherichia coli is frequently used as a convenient host organism for soluble recombinant protein expression. However, additional strategies are needed for proteins with complex folding characteristics. Here, we suggested that the acidic, neutral, and alkaline isoelectric point (pI) range curves correspond to the channels of the E. coli type-II cytoplasmic membrane translocation (periplasmic translocation) pathways of twin-arginine translocation (Tat), Yid, and general secretory pathway (Sec), respectively, for unfolded and folded target proteins by examining the characteristic pI values of the N-termini of the signal sequences or the leader sequences, matching with the known diameter of the translocation channels, and analyzing the N-terminal pI value of the signal sequences of the Tat substrates. To confirm these proposed translocation pathways, we investigated the soluble expression of the folded green fluorescent protein (GFP) with short N-terminal polypeptides exhibiting pI and hydrophilicity separately or collectively. This, in turn, revealed the existence of an anchor function with a specific directionality based on the N-terminal pI value (termed as N-terminal pI-specific directionality) and distinguished the presence of the E. coli type-II cytoplasmic membrane translocation pathways of Tat, Yid, and Sec for the unfolded and folded target proteins. We concluded that the pI value and hydrophilicity of the short N-terminal polypeptide, and the total translational efficiency of the target proteins based on the DeltaGRNA value of the N-terminal coding regions are important factors for promoting more efficient translocation (secretion) through the largest diameter of the Tat channel. These results show that the short N-terminal polypeptide could substitute for the Tat signal sequence with improved efficiency. PMID- 22038595 TI - Canal wall thickness after preparation with NiTi rotary files. AB - Root canal preparation is the most important phase of endodontic procedure and it consists of adequate canal space cleaning and shaping. In recent years, rotary instruments and techniques have gained importance because of the great efficacy, speed, and safety of the preparation procedure. AIM: The aim of this research was to investigate measurement of maximal and minimal residual dentine thickness (RDT) and canal diameter after the canal preparation with different NiTi rotary files. METHODS: The research has been conducted on extracted human teeth in vitro conditions. The teeth have been divided in seven groups (20 teeth per group) depending on the kind of instruments used for root canal preparation: ProTaper, GT, ProFile, K-3, FlexMaster, hand ProTaper, and hand GT. The canals have been shaped in a crown-down manner and irrigated with 5.25% sodium hypochlorite. The roots of the teeth have been cut 1 and 3 mm from the apex. Apical preparation quality has been assessed under the polarized light microscope. RESULTS: The maximal residual dentine thickness at distance 1 mm from apex, ranged from 1.16 to 1.45 mm, and at distance 3 mm from apex, from 1.44 to 1.84 mm. The minimal dentine thickness at distance 1 mm from apex ranged from 0.52 to 0.73 mm, and at distance 3 mm from apex, from 0.66 to 0.83 mm. The canal diameters after preparation at distance 1 mm from apex ranged from 0.42 to 0.49 mm, and at distance 3 mm from apex, from 0.53 to 0.63 mm. CONCLUSIONS: There was no significant difference neither in maximal and minimal RDT, nor in canal diameters shaped with different NiTi instruments tested. All tested NiTi files have accomplished good quality preparation of apical root canal parts. PMID- 22038596 TI - Chromium-silicon multiple bonds: the chemistry of terminal N-heterocyclic-carbene stabilized halosilylidyne ligands. AB - An efficient method for the synthesis of the first N-heterocyclic carbene (NHC) stabilized halosilylidyne complexes is reported that starts from SiBr(4). In the first step, SiBr(4) was treated with one equivalent of the N-heterocyclic carbene 1,3-bis[2,6-bis(isopropyl)phenyl]imidazolidin-2-ylidene (SIdipp) to give the 4,5 dihydroimidazolium salt [SiBr(3)(SIdipp)]Br (1-Br), which then was reduced with potassium graphite to afford the silicon(II) dibromide-NHC adduct SiBr(2)(SIdipp)(2-Br) in good yields. Heating 2-Br with Li[CpCr(CO)(3)] afforded the complex [Cp(CO)(2)Cr=SiBr(SIdipp)] (3-Br) upon elimination of CO. Complex 3 Br features a trigonal-planar-coordinated silicon center and a very short Cr?Si double bond. Similarly, the reaction of SiCl(2)(SIdipp) (2-Cl) with Li[CpCr(CO)(3)] gave the analogous chloro derivative [Cp(CO)(2)Cr=SiCl(SIdipp)] (3-Cl). Complex 3-Br undergoes an NHC exchange with 1,3-dihydro-4,5-dimethyl-1,3 bis(isopropyl)-2H-imidazol-2-ylidene (IMe(2)iPr(2)) to give the complex [Cp(CO)(2)CrSiBr(IMe(2)iPr(2))(2)] (4-Br). Compound 4-Br features a distorted tetrahedral four-coordinate silicon center. Bromide abstraction occurs readily from 4-Br with Li[B(C(6)F(5))(4)] to give the putative silylidene complex salt [Cp(CO)(2)Cr=Si(IMe(2)iPr(2))(2)][B(C(6)F(5))(4)], which irreversibly dimerizes by means of an Si-promoted electrophilic activation of one carbonyl oxygen atom to yield the dinuclear siloxycarbyne complex [Cp(CO)Cr{(MU CO)Si(IMe(2)iPr(2))(2)}(2-)Cr(CO)Cp][B(C(6)F(5))(4)](2) (5). All compounds were fully characterized, and the molecular structures of 2-Br-5-Br were determined by single-crystal X-ray diffraction. DFT calculations of 3-Br and 3-Cl and their carbene dissociation products [Cp(CO)(2)Cr=Si-X] (X=Cl, Br) were carried out, and the electronic structures of 3-Br, 3-Cl and [Cp(CO)(2)Cr=Si-X] were analyzed by the natural bond orbital method in combination with natural resonance theory. PMID- 22038597 TI - High-sensitivity stable-isotope probing by a quantitative terminal restriction fragment length polymorphism protocol. AB - Stable-isotope probing (SIP) has proved a valuable cultivation-independent tool for linking specific microbial populations to selected functions in various natural and engineered systems. However, application of SIP to microbial populations with relatively minor buoyant density increases, such as populations that utilize compounds as a nitrogen source, results in reduced resolution of labeled populations. We therefore developed a tandem quantitative PCR (qPCR) TRFLP (terminal restriction fragment length polymorphism) protocol that improves resolution of detection by quantifying specific taxonomic groups in gradient fractions. This method combines well-controlled amplification with TRFLP analysis to quantify relative taxon abundance in amplicon pools of FAM-labeled PCR products, using the intercalating dye EvaGreen to monitor amplification. Method accuracy was evaluated using mixtures of cloned 16S rRNA genes, DNA extracted from low- and high-G+C bacterial isolates (Escherichia coli, Rhodococcus, Variovorax, and Microbacterium), and DNA from soil microcosms amended with known amounts of genomic DNA from bacterial isolates. Improved resolution of minor shifts in buoyant density relative to TRFLP analysis alone was confirmed using well-controlled SIP analyses. PMID- 22038598 TI - Macrophyte species drive the variation of bacterioplankton community composition in a shallow freshwater lake. AB - Macrophytes play an important role in structuring aquatic ecosystems. In this study, we explored whether macrophyte species are involved in determining the bacterioplankton community composition (BCC) in shallow freshwater lakes. The BCC in field areas dominated by different macrophyte species in Taihu Lake, a large, shallow freshwater lake, was investigated over a 1-year period. Subsequently, microcosm experiments were conducted to determine if single species of different types of macrophytes in an isolated environment would alter the BCC. Denaturing gradient gel electrophoresis (DGGE), followed by cloning and sequence analysis of selected samples, was employed to analyze the BCC. The DGGE results of the field investigations indicated that the BCC changed significantly from season to season and that the presence of different macrophyte species resulted in lower BCC similarities in the summer and fall. LIBSHUFF analysis of selected clone libraries from the summer demonstrated different BCCs in the water column surrounding different macrophytes. Relative to the field observations, the microcosm studies indicated that the BCC differed more pronouncedly when associated with different species of macrophytes, which was also supported by LIBSHUFF analysis of the selected clone libraries. Overall, this study suggested that macrophyte species might be an important factor in determining the composition of bacterial communities in this shallow freshwater lake and that the species-specific influence of macrophytes on BCC is variable with the season and distance. PMID- 22038599 TI - Roles of diet and the acid tolerance response in survival of common Salmonella serotypes in feces of finishing pigs. AB - The persistence of Salmonella in the environment is an important factor influencing the transmission of infection in pig production. This study evaluated the effects of acid tolerance response (ATR), organic acid supplementation, and physical properties of feed on the survival of a five-strain Salmonella mixture in porcine feces held at 4 and 22 degrees C for 88 days. Acid-adapted or non-acid adapted nalidixic acid-resistant Salmonella strains were used to inoculate feces of pigs fed four different diets, which consisted of a nonpelleted, finely ground meal feed or a finely ground, pelleted feed that was left unsupplemented or was supplemented with K-diformate. Organic acid supplementation and physical properties of feed markedly influenced Salmonella survival, but the effects were highly dependent on storage temperature; survival was unaffected by ATR. The most pronounced effects were observed at 22 degrees C, a temperature similar to that of finishing pig houses. The supplementation of meal diets with K-diformate significantly reduced the duration of survival (P < 0.1) and increased rates of decline (P < 0.0001) of salmonellae in feces compared to survival in feces of pigs fed unsupplemented meal. The pelleting of feed, compared to feeding meal, significantly reduced (P < 0.1) the duration of survival in feces held at 22 degrees C. Only minor effects of feed form and acid supplementation on survivor numbers were observed at 4 degrees C. Differences in the fecal survival of Salmonella could not be related to diet-induced changes in fecal physiochemical parameters. The predominant survival of S. enterica serovar Typhimurium DT193 and serotype 4,[5],12:i:- in porcine feces demonstrates the superior ability of these serotypes to survive in this environment. Fecal survival and transmission of Salmonella in pig herds may be reduced by dietary approaches, but effects are highly dependent on environmental temperature. PMID- 22038600 TI - Prevalence of Ca2+-ATPase-mediated carbonate dissolution among cyanobacterial euendoliths. AB - Recent physiological work has shown that the filamentous euendolithic cyanobacterium Mastigocoleus testarum (strain BC008) is able to bore into solid carbonates using Ca2+-ATPases to take up Ca2+ from the medium at the excavation front, promoting dissolution of CaCO3 there. It is not known, however, if this is a widespread mechanism or, rather, a unique capability of this model strain. To test this, we undertook a survey of multispecies euendolithic microbial assemblages infesting natural carbonate substrates in marine coastal waters of the Caribbean, Mediterranean, South Pacific, and Sea of Cortez. Microscopic examination revealed the presence of complex assemblages of euendoliths, encompassing 3 out of the 5 major cyanobacterial orders. 16S rRNA gene clone libraries detected even greater diversity, particularly among the thin filamentous forms, and allowed us to categorize the endoliths in our samples into 8 distinct phylogenetic clades. Using real-time Ca2+ imaging under a confocal laser scanning microscope, we could show that all communities displayed light dependent formation of Ca2+-supersaturated zones in and around boreholes, a staple of actively boring phototrophs. In 3 out of 4 samples, boring activity was sensitive to at least one of two inhibitors of Ca2+-ATPase transporters (thapsigargin or tert-butylhydroquinone), indicating that the Ca2+-ATPase mechanism is widespread among cyanobacterial euendoliths but perhaps not universal. Function-community structure correlations point to one particular clade of baeocyte-forming euendoliths as the potential exception. PMID- 22038601 TI - Heme-biosynthetic porphobilinogen deaminase protects Aspergillus nidulans from nitrosative stress. AB - Microorganisms have developed mechanisms to combat reactive nitrogen species (RNS); however, only a few of the fungal genes involved have been characterized. Here we screened RNS-resistant Aspergillus nidulans strains from fungal transformants obtained by introducing a genomic DNA library constructed in a multicopy vector. We found that the AN0121.3 gene (hemC) encodes a protein similar to the heme biosynthesis enzyme porphobilinogen deaminase (PBG-D) and facilitates RNS-tolerant fungal growth. The overproduction of PBG-D in A. nidulans promoted RNS tolerance, whereas PBG-D repression caused growth that was hypersensitive to RNS. PBG-D levels were comparable to those of cellular protoheme synthesis as well as flavohemoglobin (FHb; encoded by fhbA and fhbB) and nitrite reductase (NiR; encoded by niiA) activities. Both FHb and NiR are hemoproteins that consume nitric oxide and nitrite, respectively, and we found that they are required for maximal growth in the presence of RNS. The transcription of hemC was upregulated by RNS. These results demonstrated that PBG D is a novel NO-tolerant protein that modulates the reduction of environmental NO and nitrite levels by FHb and NiR. PMID- 22038602 TI - Bacteriocin production: a probiotic trait? AB - Bacteriocins are an abundant and diverse group of ribosomally synthesized antimicrobial peptides produced by bacteria and archaea. Traditionally, bacteriocin production has been considered an important trait in the selection of probiotic strains, but until recently, few studies have definitively demonstrated the impact of bacteriocin production on the ability of a strain to compete within complex microbial communities and/or positively influence the health of the host. Although research in this area is still in its infancy, there is intriguing evidence to suggest that bacteriocins may function in a number of ways within the gastrointestinal tract. Bacteriocins may facilitate the introduction of a producer into an established niche, directly inhibit the invasion of competing strains or pathogens, or modulate the composition of the microbiota and influence the host immune system. Here we review the role of bacteriocin production in complex microbial communities and their potential to enhance human health. PMID- 22038603 TI - Growth rate-dependent control in Enterococcus faecalis: effects on the transcriptome and proteome, and strong regulation of lactate dehydrogenase. AB - Enterococcus faecalis V583 was grown in a glucose-limited chemostat at three different growth rates (0.05, 0.15, and 0.4 h-1). The fermentation pattern changed with growth rate, from a mostly homolactic profile at a high growth rate to a fermentation dominated by formate, acetate, and ethanol production at a low growth rate. A number of amino acids were consumed at the lower growth rates but not by fast-growing cells. The change in metabolic profile was caused mainly by decreased flux through lactate dehydrogenase. The transcription of ldh-1, encoding the principal lactate dehydrogenase, showed very strong growth rate dependence and differed by three orders of magnitude between the highest and the lowest growth rates. Despite the increase in ldh-1 transcript, the content of the Ldh-1 protein was the same under all conditions. Using microarrays and quantitative PCR, the levels of 227 gene transcripts were found to be affected by the growth rate, and 56 differentially expressed proteins were found by proteomic analyses. Few genes or proteins showed a growth rate-dependent increase or decrease in expression across the whole range of conditions, and many showed a maximum or minimum at the middle growth rate (i.e., 0.15 h-1). For many gene products, a discrepancy between transcriptomic and proteomic data were seen, indicating posttranscriptional regulation of expression. PMID- 22038604 TI - Genome sequences and characterization of the related Gordonia phages GTE5 and GRU1 and their use as potential biocontrol agents. AB - Activated sludge plants suffer frequently from the operational problem of stable foam formation on aerobic reactor surfaces, which can be difficult to prevent. Many foams are stabilized by mycolic acid-containing Actinobacteria, the mycolata. The in situ biocontrol of foaming using phages is an attractive strategy. We describe two polyvalent phages, GTE5 and GRU1, targeting Gordonia terrae and Gordonia rubrupertincta, respectively, isolated from activated sludge. Phage GRU1 also propagates on Nocardia nova. Both phages belong to the family Siphoviridae and have similar-size icosahedral heads that encapsulate double stranded DNA genomes (~65 kb). Their genome sequences are similar to each other but markedly different from those of other sequenced phages. Both are arranged in a modular fashion. These phages can reduce or eliminate foam formation by their host cells under laboratory conditions. PMID- 22038605 TI - Endosymbiont transmission mode in bacterial leaf nodulation as revealed by a population genetic study of Psychotria leptophylla. AB - Leaf-nodulated plants are colonized by vertically inherited bacterial endosymbionts, which maintain symbioses throughout host generations. The permanent character of the interaction implies phylogenetic congruence between the host and the endosymbiont. However, the present population genetic study of Psychotria leptophylla provides evidence for a mixed symbiont transmission involving both vertical inheritance and horizontal transfers from the environment. PMID- 22038606 TI - Iron transformations induced by an acid-tolerant Desulfosporosinus species. AB - The mineralogical transformations of Fe phases induced by an acid-tolerant, Fe(III)- and sulfate-reducing bacterium, Desulfosporosinus sp. strain GBSRB4.2 were evaluated under geochemical conditions associated with acid mine drainage impacted systems (i.e., low pH and high Fe concentrations). X-ray powder diffractometry coupled with magnetic analysis by first-order reversal curve diagrams were used to evaluate mineral phases produced by GBSRB4.2 in media containing different ratios of Fe(II) and Fe(III). In medium containing Fe predominately in the +II oxidation state, ferrimagnetic, single-domain greigite (Fe3S4) was formed, but the addition of Fe(III) inhibited greigite formation. In media that contained abundant Fe(III) [as schwertmannite; Fe8O8(OH)6SO4 . nH2O], the activities of strain GBSRB4.2 enhanced the transformation of schwertmannite to goethite (alpha-FeOOH), due to the increased pH and Fe(II) concentrations that resulted from the activities of GBSRB4.2. PMID- 22038607 TI - When second best is good enough: another probabilistic look at saturation mutagenesis. AB - We developed new criteria for determining the library size in a saturation mutagenesis experiment. When the number of all possible distinct variants is large, any of the top-performing variants (e.g., any of the top three) is likely to meet the design requirements, so the probability that the library contains at least one of them is a sensible criterion for determining the library size. By using a criterion of this type, one may significantly reduce the library size and thus save costs and labor while minimally compromising the quality of the best variant discovered. We present the probabilistic tools underlying these criteria and use them to compare the efficiencies of four randomization schemes: NNN, which uses all 64 codons; NNB, which uses 48 codons; NNK, which uses 32 codons; and MAX, which assigns equal probabilities to each of the 20 amino acids. MAX was found to be the most efficient randomization scheme and NNN the least efficient. TopLib, a computer program for carrying out the related calculations, is available through a user-friendly Web server. PMID- 22038608 TI - Adhesive bond stiffness of Staphylococcus aureus with and without proteins that bind to an adsorbed fibronectin film. AB - Staphylococcus aureus is known to cause biomaterial-associated infections of implants and devices once it has breached the skin and mucosal barriers. Adhesion is the initial step in the development of a biomaterial-associated infection, and strategies to prevent staphylococcal adhesion and thus biomaterial-associated infections require understanding of the adhesive bond. The aim of this study was to compare the adhesive bond stiffnesses of two S. aureus strains with and without fibronectin-binding proteins (FnBPs) adhering to a fibronectin-coated quartz crystal microbalance (QCM) sensor surface on the basis of a coupled- resonance model. Both fibronectin adsorption and staphylococcal adhesion were accompanied by negative frequency shifts, regardless of the absence or presence of FnBPs on the staphylococcal cell surfaces. This is the opposite of the positive frequency shifts often observed for other bacterial strains adhering to bare sensor surfaces. Most likely, adhering staphylococci sink into and deform the adsorbed protein layer, creating stiff binding with the sensor surface due to an increased bacterium-substratum contact area. S. aureus 8325-4 possesses FnBPs and yields less negative frequency shifts (Deltaf) that are further away from the zero-crossing frequency than S. aureus DU5883. This suggests that FnBPs on S. aureus 8325-4 create a stiffer bond to the fibronectin coating than has been observed for S. aureus DU5883. Due to a limited window of observation, as defined by the available resonance frequencies in QCM, we could not determine exact stiffness values. PMID- 22038609 TI - Bacterial cell surface damage due to centrifugal compaction. AB - Centrifugal damage has been known to alter bacterial cell surface properties and interior structures, including DNA. Very few studies exist on bacterial damage caused by centrifugation because of the difficulty in relating centrifugation speed and container geometry to the damage caused. Here, we provide a simple, versatile method of analysis for describing the compaction of bacteria during centrifugation based on a proposed centrifugation coefficient, C. Values of C can be related to different bacterial cell surface properties. Changing the geometry of the centrifugation container or centrifugation speeds changed the value of C significantly. Initial deposition rates of Staphylococcus aureus ATCC 12600 to a glass surface decayed exponentially from 4,217 to 1,478 cm-2 s-1 with increasing C, while the proportion of staphylococci with a zeta potential of around -15 mV decreased from 97 to 58%. These surface-sensitive parameters were used independently to derive a critical centrifugation coefficient (0.040), above which centrifugation was considered to impact the outcome of surface-sensitive experiments due to cell surface damage. The critical centrifugation coefficient could successfully predict staphylococcal cell surface damage, i.e., a significant change in initial deposition rate or zeta potential distribution, in 84% of all cases included here, whereas the centrifugation speed could predict damage in only 58% of all cases. Moreover, controlling the centrifugation coefficient within narrow limits over a series of experiments yielded 43% smaller standard deviations in initial staphylococcal deposition rates than with centrifugation at fixed speeds for replicate experiments. PMID- 22038610 TI - Engineering of bacterial methyl ketone synthesis for biofuels. AB - We have engineered Escherichia coli to overproduce saturated and monounsaturated aliphatic methyl ketones in the C11 to C15 (diesel) range; this group of methyl ketones includes 2-undecanone and 2-tridecanone, which are of importance to the flavor and fragrance industry and also have favorable cetane numbers (as we report here). We describe specific improvements that resulted in a 700-fold enhancement in methyl ketone titer relative to that of a fatty acid-overproducing E. coli strain, including the following: (i) overproduction of beta-ketoacyl coenzyme A (CoA) thioesters achieved by modification of the beta-oxidation pathway (specifically, overexpression of a heterologous acyl-CoA oxidase and native FadB and chromosomal deletion of fadA) and (ii) overexpression of a native thioesterase (FadM). FadM was previously associated with oleic acid degradation, not methyl ketone synthesis, but outperformed a recently identified methyl ketone synthase (Solanum habrochaites MKS2 [ShMKS2], a thioesterase from wild tomato) in beta-ketoacyl-CoA-overproducing strains tested. Whole-genome transcriptional (microarray) studies led to the discovery that FadM is a valuable catalyst for enhancing methyl ketone production. The use of a two-phase system with decane enhanced methyl ketone production by 4- to 7-fold in addition to increases from genetic modifications. PMID- 22038611 TI - Comparison of assays for sensitive and reproducible detection of cell culture infectious Cryptosporidium parvum and Cryptosporidium hominis in drinking water. AB - This study compared the three most commonly used assays for detecting Cryptosporidium sp. infections in cell culture: immunofluorescent antibody and microscopy assay (IFA), PCR targeting Cryptosporidium sp.-specific DNA, and reverse transcriptase PCR (RT-PCR) targeting Cryptosporidium sp.-specific mRNA. Monolayers of HCT-8 cells, grown in 8-well chamber slides or 96-well plates, were inoculated with a variety of viable and inactivated oocysts to assess assay performance. All assays detected infection with low doses of flow cytometry enumerated Cryptosporidium parvum oocysts, including infection with one oocyst and three oocysts. All methods also detected infection with Cryptosporidium hominis. The RT-PCR assay, IFA, and PCR assay detected infection in 23%, 25%, and 51% of monolayers inoculated with three C. parvum oocysts and 10%, 9%, and 16% of monolayers inoculated with one oocyst, respectively. The PCR assay was the most sensitive, but it had the highest frequency of false positives with mock-infected cells and inactivated oocysts. IFA was the only infection detection assay that did not produce false positives with mock-infected monolayers. IFA was also the only assay that detected infections in all experiments with spiked oocysts recovered from Envirochek capsules following filtration of 1,000 liters of treated water. Consequently, cell culture with IFA detection is the most appropriate method for routine and sensitive detection of infectious Cryptosporidium parvum and Cryptosporidium hominis in drinking water. PMID- 22038612 TI - Effect of honey on Streptococcus mutans growth and biofilm formation. AB - Because of the tradition of using honey as an antimicrobial medicament, we investigated the effect of natural honey (NH) on Streptococcus mutans growth, viability, and biofilm formation compared to that of an artificial honey (AH). AH contained the sugars at the concentrations reported for NH. NH and AH concentrations were obtained by serial dilution with tryptic soy broth (TSB). Several concentrations of NH and AH were tested for inhibition of bacterial growth, viability, and biofilm formation after inoculation with S. mutans UA159 in 96-well microtiter plates to obtain absorbance and CFU values. Overall, NH supported significantly less (P < 0.05) bacterial growth than AH at 25 and 12.5% concentrations. At 50 and 25% concentrations, both honey groups provided significantly less bacterial growth and biofilm formation than the TSB control. For bacterial viability, the results for all honey concentrations except 50% NH were not significantly different from those for the TSB control. NH was able to decrease the maximum velocity of S. mutans growth compared to AH. In summary, NH demonstrated more inhibition of bacterial growth, viability, and biofilm formation than AH. This study highlights the potential antibacterial properties of NH and could suggest that the antimicrobial mechanism of NH is not solely due to its high sugar content. PMID- 22038613 TI - Immobilisation of laccase on Eupergit supports and its application for the removal of endocrine disrupting chemicals in a packed-bed reactor. AB - Laccase from Myceliophthora thermophila was covalently immobilised on Eupergit C and Eupergit C 250L yielding specific activities of up to 17 and 80 U/g, respectively. Due to its superior activity, Eupergit C 250L was chosen for further research. The somewhat lower catalytic efficiency (based on the ratio between the turnover number and the Michaelis constant, k(cat)/K(M)) of the immobilised enzyme in comparison with that of the free enzyme was balanced by its increased stability and broader operational window related to temperature and pH. The feasibility of the immobilised laccase was tested by using a packed bed reactor (PBR) operating in consecutive cycles for the removal of Acid Green 27 dye as model substrate. High degrees of elimination were achieved (88, 79, 69 and 57% in 4 consecutive cycles), while the levels of adsorption on the support varied from 18 to 6%, proving that dye removal took place mainly due to the action of the enzyme. Finally, a continuous PBR with the solid biocatalyst was applied for the treatment of a solution containing the following endocrine disrupting chemicals: estrone (E1), 17beta-estradiol (E2) and 17alpha ethinylestradiol (EE2). At steady-state operation, E1 was degraded by 65% and E2 and EE2 were removed up to 80% and only limited adsorption of these compounds on the support, between 12 and 22%, was detected. In addition, a 79% decrease in estrogenic activity was detected in the effluent of the enzymatic reactor while only 14% was attained by inactivated laccase. PMID- 22038614 TI - Lidocaine treatment during synapse reformation periods permanently inhibits NGF induced excitation in an identified reconstructed synapse of Lymnaea stagnalis. AB - PURPOSE: Nerve growth factor (NGF) has been reported to affect synaptic transmission and cause neuropathic pain. In contrast, lidocaine has been used to reduce neuropathic pain; however, the effect of NGF and lidocaine on spontaneous transmitter release and synapse excitation has not been fully defined. Therefore, the effect of NGF and lidocaine on nerve regeneration, synapse reformation, and subsequent spontaneous transmitter release was investigated. We used Lymnaea stagnalis soma-soma-identified synaptic reconstruction to demonstrate that a transient increase in both frequency and amplitude of spontaneous events of miniature endplate potentials (MEPPs) occurs following NGF treatment and a short burst of action potentials in the presynaptic cell; in addition, the effect of lidocaine on NGF-induced synapse reformation was investigated. METHODS: Using a cell culture and electrophysiological and FM-143 imaging techniques for exocytosis on unequivocally identified presynaptic visceral dorsal 4 (VD4) and postsynaptic somata left pedal (LPeE) neurons from the mollusc Lymnaea stagnalis, the effects of NGF and lidocaine on nerve regeneration, synapse reformation, and its electrophysiological spontaneous synaptic transmission between cultured neurons were described. RESULTS: NGF increased axonal growth, frequency, and amplitudes of MEPPs. Lidocaine exposure during synapse reformation periods was drastically and permanently reduced axonal growth and the incidence of synapse excitation by NGF. CONCLUSION: NGF increased amplitudes and frequencies of MEPPs and induced synaptic excitation by increasing axonal growth and exocytosis. Lidocaine exposure during synapse reformation periods permanently suppressed NGF induced excitation by suppressing axonal growth and exocytosis of presynaptic neurons in the identified reconstructed synapse of L. stagnalis. PMID- 22038615 TI - Clinical dose of lidocaine destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron. AB - PURPOSE: Although lidocaine-induced cell toxicity has been reported, its mechanism is unclear. Cell size, morphological change, and membrane resistance are related to homeostasis and damage to the cell membrane; however, the effects of lidocaine on these factors are unclear. Using an identified LPeD1 neuron from Lymnaea stagnalis, we sought to determine how lidocaine affects these factors and how lidocaine is related to damage of the cell membrane. METHODS: Cell size and morphological form were measured by a micrograph and imaging analysis system. Membrane potential and survival rate were obtained by intracellular recording. Membrane resistance and capacitance were measured by whole-cell patch clamp. Phosphatidyl serine and nucleic acid were double stained and simultaneously measured by annexin V and propidium iodide. RESULTS: Lidocaine at a clinical dose (5-20 mM) induced morphological change (bulla and bleb) in the neuron and increased cell size in a concentration-dependent manner. Membrane potential was depolarized in a concentration-dependent manner. At perfusion of more than 5 mM lidocaine, the depolarized membrane potential was irreversible. Lidocaine decreased membrane resistance and increased membrane capacitance in a concentration-dependent manner. Both phosphatidyl serine and nucleic acid were stained under lidocaine exposure in a concentration-dependent manner. CONCLUSIONS: A clinical dose of lidocaine greater than 5 mM destroys the cell membrane and induces both necrosis and apoptosis in an identified Lymnaea neuron. PMID- 22038616 TI - Nystagmus caused by epidural fentanyl. AB - Anesthesiologists commonly use opioids for pain control in the operating room and postanesthesia care unit, and are constantly vigilant in looking for possible adverse outcomes. Therefore, common complications such as nausea, vomiting, and pruritus are well known. However, neurologic complications after opioid administration are relatively rare except for reduced consciousness, for example drowsiness or sedation. We recently experienced a case in which a 73-year-old woman presented predominantly vertical nystagmus as a neurological complication after epidural administration of fentanyl. A few previous reports on opioids as causative agents for nystagmus have all after use of epidural morphine, and there are yet no publications reporting epidural fentanyl as the cause of nystagmus. Physicians should keep in mind that epidural fentanyl could cause the nystagmus as a neurological complication even though it is used within conventional dosage ranges, although this is very rare. Also, when a patient develops nystagmus after epidural fentanyl, it could be a benign side effect caused by epidural fentanyl as we have experienced, but it could also be a sign of serious central nervous system lesions especially in patients with underlying risk factors such as old age, diabetes mellitus, hypertension, and cerebrovascular disease, and thus special attention should be paid to this. PMID- 22038617 TI - Cardiac arrest after spinal anesthesia in a patient with neurally mediated syncope. AB - We present the case of cardiac arrest in a patient with neurally mediated syncope (NMS). A 66-year-old male patient was scheduled to undergo right inguinal hernioplasty. He had a history of syncope, which occurred a few times a year in childhood and once a year recently. One minute after the second spinal injection, cardiac arrest (asystole) developed. Sinus rhythm was restored by cardiac massage and intravenous administration of atropine and ephedrine. The operation was cancelled. The patient was diagnosed as NMS by a cardiologist. Four months later, right inguinal hernioplasty was performed, uneventfully, under general anesthesia. High sympathetic blockade due to spinal anesthesia and transient withdrawal of sympathetic tone and increase in vagal discharge due to NMS could be the main causes of the cardiac arrest. If the patient has any possibility of NMS, anesthesiologists should consider the possibility of cardiac arrest after spinal anesthesia. PMID- 22038618 TI - The antinociceptive effect of intrathecal tramadol in rats: the role of alpha 2 adrenoceptors in the spinal cord. AB - PURPOSES: The alpha 2 (alpha(2))-adrenoceptor is highly important in the antinociception of tramadol administered systemically and intrathecally. However, it is unclear whether tramadol at the spinal level exerts an antinociceptive effect by directly binding with alpha(2)-adrenoceptors in the spinal cord. This study was conducted to investigate the relationship between alpha(2) adrenoceptors and the antinociception of tramadol at the spinal level. METHODS: The rat formalin test was designed to determine whether the intrathecal alpha(2) adrenoceptor antagonist yohimbine could reverse the antinociceptive effect of intrathecal tramadol. The binding affinity of tramadol for alpha(2)-adrenoceptors in the spinal cord was determined by radioligand binding assay using the labeled alpha(2)-adrenoceptor antagonist [(3)H]-yohimbine. RESULTS: The nociceptive test showed that intrathecal tramadol induced significant antinociception whereas pretreatment with intrathecal yohimbine partially reversed this antinociception. Scatchard analysis of the binding data showed [(3)H]-yohimbine had high affinity (K(d) = 1.79 nM: ) for the alpha(2)-adrenoceptor in the rat spinal cord, and that tramadol inhibited specific binding of [(3)H]-yohimbine with the spinal cord membranes with a high affinity constant (K(i) = 34.14 MUM: ) and an IC50 of 68.25 MUM: , which indicated that tramadol was much less potent than [(3)H]-yohimbine at binding with alpha(2)-adrenoceptors of the spinal cord. CONCLUSION: The results suggested that, with very weak binding affinity for alpha(2) adrenoceptors, the antinociception of intrathecal tramadol is partially related to alpha(2)-adrenoceptors, and its intrathecal antinociception may mainly involve its indirect activation of alpha(2)-adrenoceptors in the spinal cord. PMID- 22038619 TI - Spontaneous brain activity changes in children with primary monosymptomatic nocturnal enuresis: a resting-state fMRI study. AB - Primary monosymptomatic nocturnal enuresis (PMNE) is a common disorder in school aged children. However, little is known about resting-state neural function in individuals with PMNE. In this work, resting-state functional magnetic resonance imaging (fMRI) was used to investigate changes in spontaneous brain activity in children with PMNE. We analyzed resting-state fMRI data using statistical parametric mapping (SPM) and a resting-state fMRI data analysis toolkit (REST). Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) values were calculated to analyze spontaneous brain activity in 16 children with PMNE and 16 healthy controls. Children with PMNE exhibited significant differences in ALFF or ReHo in the left inferior frontal gyrus, medial frontal gyrus (Brodmann area, BA 10), and left midbrain. Abnormalities in BA 10 and the inferior frontal gyrus may affect children's decision-making with regard to voiding; abnormalities in the midbrain in PMNE children may influence the internal signal transmission in their bladder control network. Our data indicate that, in children with PMNE, several brain areas related to the micturate control network undergo developmental delay. PMID- 22038620 TI - Trilineage myelodysplasia and hemophagocytosis associated with systemic lupus erythematosus. PMID- 22038622 TI - Surface instability of a thin electrolyte film undergoing coupled electroosmotic and electrophoretic flows in a microfluidic channel. AB - We consider the stability of a thin liquid film with a free charged surface resting on a solid charged substrate by performing a general Orr-Sommerfeld (O-S) analysis complemented by a long-wave (LW) analysis. An externally applied field generates an electroosmotic flow (EOF) near the solid substrate and an electrophoretic flow (EPF) at the free surface. The EPF retards the EOF when both the surfaces have the same sign of the potential and can even lead to the flow reversal in a part of the film. In conjunction with the hydrodynamic stress, the Maxwell stress is also considered in the problem formulation. The electrokinetic potential at the liquid-air and solid-liquid interfaces is modelled by the Poisson-Boltzmann equation with the Debye-Huckel approximation. The O-S analysis shows a finite-wavenumber shear mode of instability when the inertial forces are strong and an LW interfacial mode of instability in the regime where the viscous force dominates. Interestingly, both the modes are found to form beyond a critical flow rate. The shear (interfacial) mode is found to be dominant when the film is thick (thin), the electric field applied is strong (weak), and the zeta potentials on the liquid-air and solid-liquid interfaces are high (small). The LW analysis predicts the presence of the interfacial mode, but fails to capture the shear mode. The change in the propagation direction of the interfacial mode with the zeta-potential is predicted by both O-S and LW analyses. The parametric range in which the LW analysis is valid is thus demonstrated. PMID- 22038621 TI - Three-dimensional deuterium-carbon correlation experiments for high-resolution solid-state MAS NMR spectroscopy of large proteins. AB - Well-resolved (2)H-(13)C correlation spectra, reminiscent of (1)H-(13)C correlations, are obtained for perdeuterated ubiquitin and for perdeuterated outer-membrane protein G (OmpG) from E. coli by exploiting the favorable lifetime of (2)H double-quantum (DQ) states. Sufficient signal-to-noise was achieved due to the short deuterium T (1), allowing for high repetition rates and enabling 3D experiments with a (2)H-(13)C transfer step in a reasonable time. Well-resolved 3D (2)H(DQ)-(13)C-(13)C correlations of ubiquitin and OmpG were recorded within 3.5 days each. An essentially complete assignment of (2)H(DQalpha) shifts and of a substantial fraction of (2)H(DQbeta) shifts were obtained for ubiquitin. In the case of OmpG, (2)H(DQalpha) and (2)H(DQbeta) chemical shifts of a considerable number of threonine, serine and leucine residues were assigned. This approach provides the basis for a general heteronuclear 3D MAS NMR assignment concept utilizing pulse sequences with (2)H(DQ)-(13)C transfer steps and evolution of deuterium double-quantum chemical shifts. PMID- 22038623 TI - Pacing to reduce refractory angina in patients with severe coronary artery disease: a crossover pilot trial. AB - Biventricular pacing (BiV) has been shown to reduce wall stress and workload in regions near the pacing sites. This trial investigated if BiV near the ischemic region would reduce chest pain in patients with refractory angina due to severe coronary artery disease (CAD). Eleven patients were implanted with BiV devices with leads positioned at or adjacent to their ischemic regions as detected by single-photon emission computed tomography (SPECT) and randomized to either pacing turned ON or OFF for 3 months, and then crossed over for 3 months. With pacing turned ON, a Dynamic atrioventricular (AV) delay was set for approximately 90% and 70% of the intrinsic AV delay at the resting heart rate and at the onset of symptoms, respectively. One patient was excluded from the analysis due to a large amount of RV pacing during the OFF periods (24-64%) and due to an inability to properly deliver therapy because of an excessive number of ventricular premature complexes. Overall, with the device ON vs. OFF, the number of angina episodes (0.8 +/- 0.4 vs. 1.2 +/- 0.7 per week, P = 0.03) and amount of nitroglycerin used (0.2 +/- 0.1 vs. 1.0 +/- 0.7 per week, P = 0.11) was lower with BiV pacing. Furthermore, the treadmill exercise time to symptoms trended higher (427 +/- 65 vs. 408 +/- 64 s, P = 0.19), and the sum of fluorodeoxyglucose positron emission tomography (FDG-PET) scores trended lower (7.9 +/- 3.5 vs. 12.0 +/- 4.0, P = 0.11) with the device ON vs. OFF. Nevertheless, there were no significant differences in SPECT myocardial perfusion scores, left ventricle ejection fraction, wall motion score index, and quality of life scores with device programmed ON vs. OFF (all P > 0.05). In conclusion, this pilot study demonstrated that BiV-P at or near the ischemic region was feasible and associated with significant reductions in angina in patients with severe CAD. Adequately powered prospective studies are needed to confirm these findings. PMID- 22038624 TI - The calcium-sensing receptor promotes adipocyte differentiation and adipogenesis through PPARgamma pathway. AB - Adipocyte differentiation and adipogenesis are closely related to obesity and obesity-induced metabolic disorders. The calcium-sensing receptor (CaSR) has been reported to play an antilipolytic role in human adipocyte and regulate cell differentiation in many tissues. However, the effects of CaSR on adipocyte differentiation and adipogenesis have not been clarified. In the study, we observed that activation of CaSR significantly promoted adipocyte differentiation and adipogenesis in human SW872 adipocytes. Gene expression analysis revealed that the CaSR activation increased the transcription factor proliferator activated receptor gamma (PPARgamma) and its downstream genes including CCAAT element binding protein alpha (C/EBPalpha), adipose fatty acid-binding protein (aP2), and lipoprotein lipase. The activity of glycerol-3-phosphate dehydrogenase was also increased after the stimulation of CaSR. In addition, levels of cyclic AMP and calcium which have been shown to regulate PPARgamma gene expression were significantly affected by the activation of CaSR. These effects could be suppressed by CaSR small interfering RNA (CaSR-siRNA). In conclusion, our findings suggest that activation of CaSR promotes differentiation and adipogenesis in adipocytes, which might be achieved by upregulating PPARgamma and its downstream gene expressions. Therefore, CaSR in adipocytes may be involved in the pathogenesis of obesity by promoting adipocyte differentiation and adipogenesis. PMID- 22038625 TI - Arginine decreases peroxisome proliferator-activated receptor-gamma activity via c-Jun. AB - We have previously shown in the post ischemic gut that enteral arginine enhanced injury and inflammation via c-Jun/AP-1 and abrogated peroxisome proliferator activated receptor (PPAR) gamma activity. In the current study, we investigated the mechanism by which arginine inhibited PPARgamma in vitro in rat small bowel epithelial IEC-6 cells. Arginine repressed PPARgamma transcriptional activity in a time and dose-dependent fashion. Furthermore, downregulation of PPARgamma by arginine involved phosphorylation of c-Jun that occurred before to changes in PPARgamma transcriptional activity. Silencing of c-Jun increased PPARgamma beyond that of nonsilenced cells and was not mitigated by arginine. Using a series of blocking studies, we found no relationship between arginine and the ligand dependent binding site of PPARgamma. In conclusion, arginine decreased PPARgamma transcriptional activity in small bowel intestinal epithelial cells. These changes are due, in part, to phosphorylation of c-Jun and may explain the deleterious effects of enteral arginine in the post ischemic gut. PMID- 22038626 TI - NOTCH1 regulates migration and invasion of skin cancer cells by E-cadherin repression. AB - NOTCH1 is a regulator that functions not only in tissue development, but also in cancer pathogenesis. We hypothesized that NOTCH1 is involved in skin cancer cell migration and invasion through regulation of E-cadherin and its transcription factor, Snail. Here, using immunofluorescence and western blots, we show that NOTCH1 is upregulated in skin cancer tissue on skin. Inhibition or activation of NOTCH1 altered expression of E-cadherin and Snail in the skin cancer cell line A431. Our results suggest that this effect is through changing DNA methylation levels of the E-cadherin gene promoter. Activation and inhibition of NOTCH1 also altered the behavior of A431 cells in migration and invasion assays in vitro. Our results suggest NOTCH1 is a potential target for discovery of new drug to inhibit skin cancer metastasis. PMID- 22038627 TI - The non-receptor tyrosine kinase c-Src mediates the PDGF-induced association between Furin and pro-MT1-MMP in HPAC pancreatic cells. AB - Furin is a member of the proprotein convertase family, which is capable of cleaving the precursors of a wide variety of substrates including membrane-type 1 matrix metalloproteinase (MT1-MMP) proenzyme. c-Src is activated by growth factors, and has been linked with a poor prognosis in pancreatic cancer (PCa). Both c-Src and Furin play crucial roles in tumorigenesis, and the mechanism controlling their association is not understood. Modulation of the association between Furin and pro-MT1-MMP by c-Src inhibitor PP2 was evaluated by western blotting, assay of in vitro enzyme, co-immunoprecipitation (co-IP), and confocal immunofluorescence microscopy. Human platelet-derived growth factor BB (PDGF-BB) activated c-Src and induced c-Src-dependent association of Furin with pro-MT1-MMP in HPAC pancreatic cancer cells. Co-IP and confocal immunofluorescence assays revealed that c-Src interacts with Furin in vivo. The SH2 domain appeared to be important for c-Src interaction with Furin. In addition, we showed that Furin protein is tyrosine phosphorylated. Association between Furin and MT1-MMP is regulated by the tyrosine kinase c-Src. PMID- 22038628 TI - Claudin-5 participates in the regulation of endothelial cell motility. AB - A key step in metastasis is the interaction and penetration of the vascular endothelium by cancer cells. Tight Junctions (TJ) are located between the cancer epithelial cells and between the endothelial cells functioning in an adhesive manner. They represent a critical barrier which the cancer cells must overcome in order to penetrate and initiate metastasis. Claudin-5 is a protein member of the Claudin family, a group of TJ proteins expressed in both endothelial and epithelial cells. This study examined in vitro the effect of altering levels of expression of Claudin-5 in HECV cells. Insertion of Claudin-5 gene in HECV cells resulted in cells that were significantly less motile and less adhesive to matrix (P < 0.001). These cells also exhibited a significant decreased in the angiogenic potential (P < 0.001). Results also revealed a link between Claudin-5 and cell motility. Furthermore, a possible link between Claudin-5 and N-WASP, and Claudin 5 and ROCK was demonstrated when interactions between these proteins were seen in the cell line. Moreover, followed by treatment of N-WASP inhibitor (Wiskostatin) and ROCK inhibitor (Y-27632), cell motility and angiogenic potential were assessed in response to the inhibitors. Results showed that the knockdown of Claudin-5 in HECV cells masked their response to both N-WASP and ROCK inhibitors. In conclusion, this study portrays a new and interesting role for Claudin-5 in cell motility involving the N-WASP and ROCK signalling cascade which is beyond the primarily role of Claudin-5 in keeping the cell barrier tight as it was originally reported. PMID- 22038629 TI - Regional differences in sexually dimorphic protein expression in the spontaneously hypertensive rat (SHR). AB - Hypertension is sexually dimorphic and modified by removal of endogenous sex steroids. This study tested the hypothesis that endogenous gonadal hormones exert differential effects on protein expression in the kidney and mesentery of SHR. At ~5 weeks of age male and female SHR underwent sham operation, orchidectomy, or ovariectomy (OVX). At 20-23 weeks of age, mean arterial pressure (MAP) was measured in conscious rats. The mesenteric arterial tree and kidneys were collected, processed for Western blots, and probed for Cu Zn superoxide dismutase (SOD1), soluble epoxide hydrolase (sEH), and Alpha 2A adrenergic receptor (A2AR) expression. MAP was unaffected by ovariectomy (Sham 164 +/- 4: Ovariecttomy 159 +/- 3 mm Hg). MAP was reduced by orchidectomy (Sham 189 +/- 5:Orchidectomy 167 +/ 2 mm Hg). In mesenteric artery, SOD1 expression was greater in male versus female SHR. Orchidectomy increased while ovariectomy decreased SOD1 expression. The kidney exhibited a different pattern of response. SOD1 expression was reduced in male compared to female SHR but gonadectomy had no effect. sEH expression was not significantly different among the groups in mesenteric artery. In kidney, sEH expression was greater in males compared to females. Ovariectomy but not orchidectomy increased sEH expression. A2AR expression was greater in female than male SHR in mesentery artery and kidney. Gonadectomy had no effect in either tissue. We conclude that sexually dimorphic hypertension is associated with regionally specific changes in expression of three key proteins involved in blood pressure control. These data suggest that broad spectrum inhibition or stimulation of these systems may not be the best approach for hypertension treatment. Instead regionally targeted manipulation of these systems should be investigated. PMID- 22038631 TI - [Imaging in the emergency room]. AB - In order to reduce mortality in severely injured patients, a rapid radiologic diagnosis is essential. Sonography plays a role only as a focused assessment with sonography for trauma (FAST) to clarify free intraperitoneal fluid immediately on admittance. Today, whole-body multislice helical computed tomography (CT) has become increasingly important as a diagnostic tool. Based on the results of the CT scan, patients can be referred for laparotomy or safely classified for "wait and see" treatment. Although the reduction in injury-related mortality would outweigh the risk of radiation dose, the indiscriminate use of CT for patients with minor injuries is not justified and must be avoided. PMID- 22038632 TI - [Triple rule-out computed tomography in emergency departments]. AB - In the emergency department patients with chest pain play an important role because the underlying and concealed diseases can be life-threatening. The complaints are often nonspecific and patients also have different risk profiles. In patients in the emergency department with nonspecific chest pain a"1-stop strategy" for elucidation of the three main organs lung, hear and aorta with the 4 main differential diagnoses (aortic dissection, ruptured aortic aneurysm, pulmonary embolism and coronary heart disease) is desirable. Technical advances in computed tomography (CT) in recent years make this approach technically possible. In modern emergency departments CT equipment is becoming more and more common in order to rapidly examine trauma patients. A meaningful patient selection and preparation are, however, necessary to avoid unnecessary exposure of patients to contrast media and radiation. In this way it is possible to reduce the rate of overlooked diseases or false diagnoses. PMID- 22038633 TI - [Thoracic radiology in the intensive care unit]. AB - The clinical evaluation of the intensive care unit patient is based upon multiple parameters, including portable chest x-ray examination. Knowledge of the methods, capabilities, and limitations is prerequisite for a legally correct and medically reasonable approach. This report provides basic knowledge about pleural und pulmonary pathologies, e.g., pneumothorax, pleural effusion, atelectasis, aspiration, pneumonia, lung edema, and acute respiratory distress syndrome. PMID- 22038634 TI - [Radiology in pediatric intensive care units]. AB - The role of diagnostic imaging in pediatric intensive care units (PICU) includes primary diagnosis, monitoring of the patient's progress, and the assessment of interventional procedures. Images should be acquired in the PICU, not only to minimize the time interval between image acquisition and image interpretation but also in order to avoid unnecessary and maybe harmful transportation of the patient. Portable, optimized equipment is warranted. Most images are acquired as conventional X-ray examinations. Thorough consideration of radiation protection based on optimized equipment also includes the protection of relatives and other children in the PICU room. Ultrasound is an expanding imaging modality adjunct or as alternative to conventional X-ray examinations, which allows the generation of functional information (color-coded duplex, elastography). Fluoroscopy, computed tomography, and magnetic resonance imaging are available as advanced diagnostic modalities in special circumstances, but require transportation of the patient. PMID- 22038635 TI - [Acute kidney injury after cardiac surgery : early diagnosis with neutrophil gelatinase-associated lipocalin]. AB - In current clinical practice, the diagnosis of acute kidney injury (AKI) is based on markers of renal function, e.g., an increase in serum creatinine or a decrease in urine output. Biomarkers for the early detection of structural renal damage are still not available. This dilemma may have considerably contributed to the delayed development of effective therapies and poor prognosis for the affected patients. The measurement of novel renal damage biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), enables a 24 to 48-hour earlier diagnosis of AKI after cardiac surgical procedures. Based on the presence of a biomarker, potentially effective treatments may be initiated or nephrotoxins withdrawn. In addition, NGAL may also provide valuable information for patient management. Currently, no clear NGAL cut-off has been established, thus, impeding its clinical implementation. Prior to a change of guidelines, multicenter randomized studies, using NGAL as an entry criterion, should prove a benefit for the patients or a favorable cost-benefit ratio. PMID- 22038636 TI - [Patients with minor injuries in a Berlin inner-city emergency room : substance misuse, residential area, and sociodemographics]. AB - BACKGROUND: The aim of this post hoc study was to evaluate the association of substance use disorders (SUD) and residential neighborhood affiliation in a group of patients with minor injuries presenting to an inner-city emergency room (ER) in Berlin. METHODS: A total of 2,716 patients with minor injuries presenting to the ER were evaluated concerning alcohol use disorders (AUDIT, cut-off: males 8 points, females 5 points), smoking status, and illicit drug use in the past year. Information about residential area (zip code) and sociodemographics (paper-pencil questionnaire) were also obtained. RESULTS: With respect to residential area, significant differences concerning SUD were identified: from the perspective of the inner-city ER, living close to the ER was associated with substance misuse. Here, alcohol use disorders (AUD), smokers, and illicit drug use were found more frequently compared to patients living in the periphery of the city. In addition, patients living close to the ER were more often unemployed, had a lower income, or were students. CONCLUSION: There are differences in SUD with respect to residential area. However, in order to be able to draw reliable conclusions, an approach collecting representative data at the city district level as well as using a multicenter approach at the city ER level is necessary. PMID- 22038637 TI - [Prophylactic intraaortic balloon pumping in high-risk cardiac surgery patients]. AB - BACKGROUND: We examined the impact of prophylactic IABP insertion in EuroSCORE stratified high-risk cardiac surgery patients with a score >=8. MATERIAL AND METHODS: A randomized trial with 104 patients either without prophylactic IABP insertion (group A, n=52) or with IABP (group B, n=52) was conducted. The primary endpoint was 30-day mortality. RESULTS: The median age of the patients was 74 years and 43% of participants were females. The 30-day mortality did not differ between group A (17.3%) and group B (13.4%; p=0.78). The median hospital stay was 14 days in both groups. Intra- and postoperative IABP support was required by 13 patients (21%) in group A. The median ventilation time (14 hours versus 13 hours), median catecholamine dose, frequency of dialysis-dependent acute renal failure (28% versus 18%), cardiac indices, and frequency of a low cardiac output syndrome (26% versus 25%) did not significantly differ between groups. CONCLUSION: Prophylactic preoperative IABP insertion in EuroSCORE-stratified high risk patients is not associated with decreased 30-day mortality. PMID- 22038638 TI - Successful bridge to recovery using a microaxial blood pump in a patient with electrical storm and cardiogenic shock. AB - A 59-year-old patient with dilated cardiomyopathy and incessant ventricular tachycardia leading to progressive cardiogenic shock is presented. Due to hemodynamic instability, high dose catecholamines were required in addition to the implantation of an intraaortic balloon pump (IABP), which, however, appeared to further augment the frequency and duration of ventricular tachycardias. The implantation of a microaxial blood pump allowed catecholamine administration to be terminated, thereby, ending this vicious circle of catecholamine-driven electrical storm. Within 5 days, the patient was hemodynamically stabilized and kidney and liver function recovered with the support of intensive antiarrhythmic therapy (amiodarone, mexiletine, sotalol). During a 24-month follow-up, the patient had no further ICD shocks and no rehospitalization was required for treatment of congestive heart failure. PMID- 22038639 TI - [Ethical aspects in end-of-life care]. AB - Therapy decisions in the care of critically ill and dying patients in intensive care and emergency medicine must reflect probably conflicting issues of medical indications, ethics and law. This is of particular relevance when treatment preferences of patients are not known or are in contrast to those of the carers. Difficulties regarding prognostication or with determining the beginning of an irreversible dying process may also lead to treatment situations that need ethical reflection. It is recommended to tackle medico-ethical issues by discussion of the meaning of relevant terms and medico-ethical principles, analyzing the professional self-image in intensive care and emergency medicine, consideration of options of palliative medicine and by use of an ethics case consultation. PMID- 22038642 TI - Chiral Bronsted acid catalyzed stereoselective addition of azlactones to 3 vinylindoles for facile access to enantioenriched tryptophan derivatives. AB - Syn-gled out: The syn diastereo- and enantioselective addition of azlactones to 3 vinylindoles was accomplished by using a chiral, binapthol-derived, Bronsted acid catalyst (see scheme). This method enables facile access to tryptophan derivatives with adjacent quaternary and tertiary stereogenic centers, which are potentially useful for the synthesis of peptidomimetics. PMID- 22038641 TI - Lessons from the past: opportunities to improve childhood cancer survivor care through outcomes investigations of historical therapeutic approaches for pediatric hematological malignancies. AB - Investigations of long-term outcomes have been instrumental in designing safer and more effective contemporary therapies for pediatric hematological malignancies. Despite the significant therapeutic changes that have occurred over the last five decades, therapy modifications largely represent refinements of treatment protocols using agents and modalities that have been available for more than 30 years. This review summarizes major trends in the evolution of treatment of pediatric hematological malignancies since 1960 to support the relevance of the study of late effects of historical therapeutic approaches to the design and evaluation of contemporary treatment protocols and the follow-up of present-day survivors. PMID- 22038643 TI - Effects of TRPV4 cation channel activation on the primary bladder afferent activities of the rat. AB - AIMS: Transient receptor potential vanilloid 4 (TRPV4) may affect afferent pathways innervating the bladder. We investigated the effects of GSK1016790A (GSK) and RN1734, a TRPV4 agonist and antagonist, respectively, and P2X purinoceptor antagonists (TNP-ATP and PPADS) on cystometry (CMG), and the effect of GSK on single afferent fiber activities (SAAs) of the rat bladder and its relationship with capsaicin (Cap)-sensitivity. METHODS: Conscious female Sprague Dawley rats were used for CMG measurements. In SAA measurements, under urethane anesthesia, SAA was identified by electrical stimulation of the pelvic nerve and by bladder distention. Cystometric parameters were measured before and after intravesical drug instillation. In SAA measurements, response with saline instillation served as baseline. Then, GSK was instilled three times, and finally Cap was instilled to investigate the relationship with Cap-sensitivity. RESULTS: Intravesical GSK-instillation transiently decreased bladder capacity and voided volume, which were counteracted by RN1734, TNP-ATP, and PPADS. In SAA measurements, Adelta-fibers (n = 7) were not affected by either GSK or Cap. Based on the Cap-sensitivity, C-fibers could be divided into two subtypes: Cap insensitive (n = 14) and Cap-sensitive (n = 8). In the Cap-insensitive C-fibers, GSK significantly increased the SAAs during the first instillation, but the increase attenuated with time, whereas GSK did not significantly affect the Cap sensitive C-fibers. CONCLUSIONS: The present results suggest that activation of TRPV4 in the bladder, probably urothelium, facilitates the micturition reflex by activation of the mechanosensitive, Cap-insensitive C-fibers of the primary bladder afferents in rats. PMID- 22038644 TI - Systematic review of services providing information and/or advice to people with dementia and/or their caregivers. AB - BACKGROUND: Information is a key part of service provision to people with dementia and their carers, but there is no systematic review of the evidence. This study aimed to determine whether information services confer significant benefit for quality of life, neuropsychiatric symptoms and carer burden. METHOD: A systematic review of intervention studies in people with dementia was carried out, focussing predominantly on the provision of information and/or advice. RESULTS: Thirteen randomised controlled trials were identified. Two of the three studies measuring quality of life indicated benefit. Significant benefits were also evident for neuropsychiatric symptoms (points difference, -1.48; confidence interval, -2.11 to 0.86), but not carer burden. Most interventions included other key elements such as skills training, telephone support and direct help to navigate the medical and care system. CONCLUSION: There is some support for the value of information services, but studies are needed to determine the specific elements that are effective. PMID- 22038645 TI - Siderophore production by actinomycetes isolates from two soil sites in Western Australia. AB - The actinomycetes are metabolically flexible soil micro-organisms capable of producing a range of compounds of interest, including siderophores. Siderophore production by actinomycetes sampled from two distinct and separate geographical sites in Western Australia were investigated and found to be generally similar in the total percentage of siderophore producers found. The only notable difference was the proportion of isolates producing catechol siderophores with only 3% found in site 1 (from the north-west of Western Australia and reportedly containing 40% magnetite) and 17% in site 2 (a commercial stone fruit orchard in the hills east of Perth with a soil base ranging from sandy loam to laterite). Further detailed characterization of isolates of interest identified a Streptomyces that produced extracellularly excreted enterobactin, the characteristic Enterobacteriaceae siderophore, and also revealed some of the conditions required for enterobactin production. Carriage of the entF gene, which codes for the synthetase responsible for the final assembly of the tri-cyclic structure of enterobactin, was confirmed by PCR in this isolate. Another separate Streptomyces produced a compound that matched the UV/VIS spectra of heterobactin, a siderophore previously only described in Rhodococcus and Nocardia. PMID- 22038646 TI - The use of selective immunosuppressive therapy on myelodysplastic syndromes in targeted populations results in good response rates and avoids treatment-related disease progression. AB - To determine the treatment response and disease progression in strictly selected patients with myelodysplastic syndrome undergoing immunosuppressive therapy (IST), patients were required to have an international prognostic scoring system [corrected] (IPSS) score <= 1.0 and at least one of the following conditions: (1) expression of the HLA-DR15 allele, (2) bone marrow (BM) cellularity of less than 30%, and (3) abnormal immune index of BM T-lymphocytes.The exclusion criteria were as follows: (1) >= 5% marrow myeloblasts, (2) poor karyotype, and (3) diagnosis of concurrent nonhematological malignancy. Patients received antithymocyte globulin followed by cyclosporine A (CsA) or CsA alone for at least 3 months. Seventy-one cases were analyzed. The total response rate was 77.5% (55/71 cases) with 11 complete responses. The response rate was positively correlated with the number of recruitment criteria met. Patients with an abnormal CD8, an abnormal CD4, or both had similar response rates. Patients who responded to treatment had significantly lower Th1 and Tc1 levels after treatment (P < 0.01 and P < 0.001, respectively), and six of eight patients with abnormal chromosomes did not show obviously abnormal clonal expansion when reassessed after IST. During the median observation period of 24 months, only two cases exhibited disease progression. At the median observation of 24 months, 35 of 55 responders (63.6%) maintained a hematological response, and 60 of 71 patients (84.5%) were still alive. The strictly selective use of IST may yield high response rates and can avoid treatment-related acute myeloid leukemia transformation. IST significantly reduces Th1 and Tc1 levels without causing malignant clonal expansion. PMID- 22038647 TI - Uncovering symmetry-breaking vector and reliability order for assigning secondary structures of proteins from atomic NMR chemical shifts in amino acids. AB - Unravelling the complex correlation between chemical shifts of (13) C (alpha), (13) C (beta), (13) C', (1) H (alpha), (15) N, (1) H ( N ) atoms in amino acids of proteins from NMR experiment and local structural environments of amino acids facilitates the assignment of secondary structures of proteins. This is an important impetus for both determining the three-dimensional structure and understanding the biological function of proteins. The previous empirical correlation scores which relate chemical shifts of (13) C (alpha), (13) C (beta), (13) C', (1) H (alpha), (15) N, (1) H ( N ) atoms to secondary structures resulted in progresses toward assigning secondary structures of proteins. However, the physical-mathematical framework for these was elusive partly due to both the limited and orthogonal exploration of higher-dimensional chemical shifts of hetero-nucleus and the lack of physical-mathematical understanding underlying those correlation scores. Here we present a simple multi-dimensional hetero nuclear chemical shift score function (MDHN-CSSF) which captures systematically the salient feature of such complex correlations without any references to a random coil state of proteins. We uncover the symmetry-breaking vector and its reliability order not only for distinguishing different secondary structures of proteins but also for capturing the delicate sensitivity interplayed among chemical shifts of (13) C (alpha), (13) C (beta), (13) C', (1) H (alpha), (15) N, (1) H ( N ) atoms simultaneously, which then provides a straightforward framework toward assigning secondary structures of proteins. MDHN-CSSF could correctly assign secondary structures of training (validating) proteins with the favourable (comparable) Q3 scores in comparison with those from the previous correlation scores. MDHN-CSSF provides a simple and robust strategy for the systematic assignment of secondary structures of proteins and would facilitate the de novo determination of three-dimensional structures of proteins. PMID- 22038648 TI - Speeding up direct (15)N detection: hCaN 2D NMR experiment. AB - Experiments detecting low gyromagnetic nuclei have recently been proposed to utilize the relatively slow relaxation properties of these nuclei in comparison to (1)H. Here we present a new type of (15)N direct-detection experiment. Like the previously proposed CaN experiment (Takeuchi et al. in J Biomol NMR 47:271 282, 2010), the hCaN experiment described here sequentially connects amide (15)N resonances, but utilizes the initial high polarization and the faster recovery of the (1)H nucleus to shorten the recycling delay. This allows recording 2D (15)N detected NMR experiments on proteins within a few hours, while still obtaining superior resolution for (13)C and (15)N, establishing sequential assignments through prolines, and at conditions where amide protons exchange rapidly. The experiments are demonstrated on various biomolecules, including the small globular protein GB1, the 22 kDa HEAT2 domain of eIF4G, and an unstructured polypeptide fragment of NFAT1, which contains many SerPro sequence repeats. PMID- 22038650 TI - Transanal specimen extraction in robotic rectal cancer surgery. AB - BACKGROUND: The aim of this study was to identify the benefits of robotic transanal specimen extraction (RTSE) compared with minilaparotomy specimen extraction (MSE). METHODS: Patients who underwent totally robotic surgery with curative intent for treatment of adenocarcinoma of the rectum below 12 cm from the anal verge were selected from the authors' database. Patients were divided into RTSE and MSE groups according to the method of specimen delivery. Clinicopathological features and perioperative surgical outcomes were compared between the two groups. RESULTS: There were 53 patients in the RTSE group and 66 in the MSE group. No differences were observed in overall complications. Postoperative recovery was faster in the RTSE group in terms of resumption of a soft diet (mean(s.d.) 3.5(1.5) versus 4.6(1.7) days; P < 0.001) and length of hospital stay (9.0(4.8) versus 11.3(5.3) days; P = 0.016). Pain scores on a visual analogue scale were significantly lower in the RTSE group than in the MSE group from day 2 to day 5 after surgery (P = 0.021 to P < 0.001). CONCLUSION: RTSE in robotic rectal cancer surgery was associated with less pain and a faster recovery than MSE. PMID- 22038649 TI - Asymmetry of (13)C labeled 3-pyruvate affords improved site specific labeling of RNA for NMR spectroscopy. AB - Selective isotopic labeling provides an unparalleled window within which to study the structure and dynamics of RNAs by high resolution NMR spectroscopy. Unlike commonly used carbon sources, the asymmetry of (13)C-labeled pyruvate provides selective labeling in both the ribose and base moieties of nucleotides using E. coli variants, that until now were not feasible. Here we show that an E. coli mutant strain that lacks succinate and malate dehydrogenases (DL323) and grown on [3-(13)C]-pyruvate affords ribonucleotides with site specific labeling at C5' (~95%) and C1' (~42%) and minimal enrichment elsewhere in the ribose ring. Enrichment is also achieved at purine C2 and C8 (~95%) and pyrimidine C5 (~100%) positions with minimal labeling at pyrimidine C6 and purine C5 positions. These labeling patterns contrast with those obtained with DL323 E. coli grown on [1, 3 (13)C]-glycerol for which the ribose ring is labeled in all but the C4' carbon position, leading to multiplet splitting of the C1', C2' and C3' carbon atoms. The usefulness of these labeling patterns is demonstrated with a 27-nt RNA fragment derived from the 30S ribosomal subunit. Removal of the strong magnetic coupling within the ribose and base leads to increased sensitivity, substantial simplification of NMR spectra, and more precise and accurate dynamic parameters derived from NMR relaxation measurements. Thus these new labels offer valuable probes for characterizing the structure and dynamics of RNA that were previously limited by the constraint of uniformly labeled nucleotides. PMID- 22038653 TI - Patient autonomy and choice in healthcare: self-testing devices as a case in point. AB - This paper aims to critique the phenomenon of advanced patient autonomy and choice in healthcare within the specific context of self-testing devices. A growing number of self-testing medical devices are currently available for home use. The premise underpinning many of these devices is that they assist individuals to be more autonomous in the assessment and management of their health. Increased patient autonomy is assumed to be a good thing. We take issue with this assumption and argue that self-testing provides a specific example how increased patient autonomy and choice within healthcare might not best serve the patient population. We propose that current interpretations of autonomy in healthcare are based on negative accounts of liberty to the detriment of a more relational understanding. We also propose that Kantian philosophy is often applied to the healthcare arena in an inappropriate manner. We draw on the philosophical literature and examples from the self-testing process to support these claims. We conclude by offering an alternative account of autonomy based on the interrelated concepts of relationality, care and responsibility. PMID- 22038655 TI - Conformationally stabilized catalysts by fluorine insertion: tool for enantioselectivity improvement. PMID- 22038654 TI - Hydrogel design for supporting neurite outgrowth and promoting gene delivery to maximize neurite extension. AB - Hydrogels capable of gene delivery provide a combinatorial approach for nerve regeneration, with the hydrogel supporting neurite outgrowth and gene delivery inducing the expression of inductive factors. This report investigates the design of hydrogels that balance the requirements for supporting neurite growth with those requirements for promoting gene delivery. Enzymatically-degradable PEG hydrogels encapsulating dorsal root ganglia explants, fibroblasts, and lipoplexes encoding nerve growth factor were gelled within channels that can physically guide neurite outgrowth. Transfection of fibroblasts increased with increasing concentration of Arg-Gly-Asp (RGD) cell adhesion sites and decreasing PEG content. The neurite length increased with increasing RGD concentration within 10% PEG hydrogels, yet was maximal within 7.5% PEG hydrogels at intermediate RGD levels. Delivering lipoplexes within the gel produced longer neurites than culture in NGF-supplemented media or co-culture with cells exposed to DNA prior to encapsulation. Hydrogels designed to support neurite outgrowth and deliver gene therapy vectors locally may ultimately be employed to address multiple barriers that limit regeneration. PMID- 22038656 TI - A woman with low HDL cholesterol and corneal opacity. PMID- 22038658 TI - Pneumobilia in chest radiograph. PMID- 22038659 TI - Optical fibre gratings as tools for chemical and biochemical sensing. AB - Optical fibre gratings have recently been suggested as optical platforms for chemical and biochemical sensing. On the basis of the measurement of refractive index changes induced by a chemical and biochemical interaction in the transmission spectrum along the fibres, they are proposed as a possible alternative to the other label-free optical approaches, such as surface plasmon resonance and optical resonators. The combination of the use of optical fibres with the fact that the signal modulation is spectrally encoded offers multiplexing and remote measurement capabilities which the other technology platforms are not able to or can hardly offer. The fundamentals of the different types of optical fibre gratings are described and the performances of the chemical and biochemical sensors based on this approach are reviewed. Advantages and limitations of optical fibre gratings are considered, with a look at new perspectives for their utilization in the field. PMID- 22038660 TI - Condensation cascades and methylgroup transfer reactions during the formation of arsane, methyl- and dimethylarsane by aqueous borohydride and (methyl) arsenates. AB - The formation of volatile products during the reaction of As(III: ), As(V: ), MeAsO(OH)(2), and Me(2)AsO(OH) with aqueous NaBH(4) has been investigated, and the formation of arsanes, diarsanes, and triarsanes has been detected. The presence of triarsanes is reported here for the first time. Diarsanes and triarsanes are likely formed in condensation cascade reactions, whereas trimethylarsane arises via the transfer of a methyl group. The formation of volatile by-products is considerably reduced by increasing the acidity of the medium and the concentration of NaBH(4) or by the addition of thiols, such as cysteine. A reaction scheme is proposed which reconciles the evidence reported herein and elsewhere in the literature that is valid for both analytical (trace analysis) and non-analytical reaction conditions. PMID- 22038661 TI - Overexpression of NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury. AB - Gliomas are the most common and devastating type of primary brain tumor. Many non neoplastic cells, including immune cells, comprise the tumor microenvironment where they create a milieu that appears to dictate cancer development. ATP and the phosphohydrolytic products ADP and adenosine by activating P2 and P1 receptors may participate in these interactions among malignant and immune cells. Purinergic receptor-mediated cell communication is closely regulated by ectonucleotidases, such as by members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, which hydrolyze extracellular nucleotides. We have shown that gliomas, unlike astrocytes, exhibit low NTPDase activity. Furthermore, ATP induces glioma cell proliferation and the co-administration of apyrase decreases progression of injected cells in vivo. We have previously shown that NTPDase2 reconstitution dramatically increases tumor growth in vivo. Here we evaluated whether NTPDase2 reconstitution to gliomas modulates systemic inflammatory responses. We observed that NTPDase2 overexpression modulated pro inflammatory cytokine production and platelet reactivity. Additionally, pathological alterations in the lungs were observed in rats bearing these tumors. Our results suggest that disruption of purinergic signaling via ADP accumulation creates an inflammatory state that may promote tumor spread and dictate clinical progression. PMID- 22038662 TI - Sorafenib exposure decreases over time in patients with hepatocellular carcinoma. AB - BACKGROUND: Intra-patient variability in sorafenib pharmacokinetics has been poorly investigated to date. We hypothesized that sorafenib clearance could decrease over time, as seen with imatinib. PATIENTS AND METHODS: Sorafenib plasma concentrations were determined by liquid chromatography, every 2 weeks, in consecutive hepatocellular carcinoma patients treated with sorafenib. Sorafenib dose-normalized area under the concentration-time curve (AUC) was determined from a population pharmacokinetics model, and its kinetics was analyzed in order to identify possible alterations of exposure over time. RESULTS: Fifteen hepatocellular carcinoma patients with Child-Pugh A cirrhosis, in whom sorafenib dosing remained unchanged from initiation of treatment to disease progression, were eligible for this analysis. Sorafenib AUC significantly decreased over time: the median AUC during the third month of treatment was lower than that observed after one month of treatment (43.0 vs. 60.3 mg/L.h, p = 0.008). Most importantly, median sorafenib AUC at the time of progression was almost two-fold lower than that observed after one month of therapy (33.2 vs. 60.3 mg/L.h, p = 0.007). These findings suggest an induction of expression of efflux transporters in the gut wall, or an induction of sorafenib metabolism. CONCLUSIONS: In patients with progressive disease in whom exposure markedly decreased from baseline, sorafenib dose escalation could be considered, aiming to restore an adequate drug exposure and possibly anti-tumor activity. PMID- 22038663 TI - A three-dimensional highly interconnected composite oxygen reduction reaction electrocatalyst prepared from a core-shell precursor. PMID- 22038664 TI - Histology, histochemistry and stereology of the adipose fin of Prochilodus lineatus. AB - The adipose fin is small, nonpared, and usually located medially between the dorsal and caudal fin. Its taxonomic occurrence is very restrict; thus, it represents an important trace for taxon distinction. As it does not play a known vital physiological roll and it is easily removed, it is commonly used in marking and recapture studies. The present study characterizes the adipose fin of Prochilodus lineatus, as it is poorly explored by the literature. The adipose fin consists basically of a loose connective core, covered by a stratified epithelium supported by collagen fibers. At the epithelium, pigmented cells and alarm substance cells are found. Despite the name, adipocytes or lipid droplets are not observed on the structure of the fin. PMID- 22038665 TI - Algorithmic modeling of the irrelevant sound effect (ISE) by the hearing sensation fluctuation strength. AB - Background sounds, such as narration, music with prominent staccato passages, and office noise impair verbal short-term memory even when these sounds are irrelevant. This irrelevant sound effect (ISE) is evoked by so-called changing state sounds that are characterized by a distinct temporal structure with varying successive auditory-perceptive tokens. However, because of the absence of an appropriate psychoacoustically based instrumental measure, the disturbing impact of a given speech or nonspeech sound could not be predicted until now, but necessitated behavioral testing. Our database for parametric modeling of the ISE included approximately 40 background sounds (e.g., speech, music, tone sequences, office noise, traffic noise) and corresponding performance data that was collected from 70 behavioral measurements of verbal short-term memory. The hearing sensation fluctuation strength was chosen to model the ISE and describes the percept of fluctuations when listening to slowly modulated sounds (f(mod) < 20 Hz). On the basis of the fluctuation strength of background sounds, the algorithm estimated behavioral performance data in 63 of 70 cases within the interquartile ranges. In particular, all real-world sounds were modeled adequately, whereas the algorithm overestimated the (non-)disturbance impact of synthetic steady-state sounds that were constituted by a repeated vowel or tone. Implications of the algorithm's strengths and prediction errors are discussed. PMID- 22038666 TI - Voluntary triggering of the first target attenuates the attentional blink. AB - The term attentional blink (AB) refers to a failure in identifying the second of two targets, separated by less than 500 ms, embedded in a rapid succession of nontargets. To examine whether the expectation of the onset of the first target affects the AB, we compared the magnitudes of the AB deficit when participants triggered the appearance of the first target and when the target was presented automatically at some time point, as in traditional AB studies. In Experiment 1, the first target appeared immediately after a participant's voluntary keypress, revealing that the accuracy for identifying the first target increased and that the AB deficit was attenuated. In Experiment 2, the temporal delay between a voluntary keypress and the first-target presentation was manipulated. The results showed that both targets could be reported accurately only when the first target was presented within 300 ms after the action. In Experiment 3, we ruled out an alternative explanation that would attribute the facilitation effect to mere physical movement, by examining the accuracy of target identification when participants voluntarily pressed a key but that action was unrelated to the onset of the first target. Taken together, the results suggest that voluntary action to trigger the onset of a visual target facilitates processing and reduces the subsequent AB deficit when the target appears within 300 ms of the action. PMID- 22038667 TI - The involvement of bottom-up saliency processing in endogenous inhibition of return. AB - Participants are faster at detecting a visual target when it appears at a cued, as compared with an uncued, location. In general, a reversal of this cost-benefit pattern is observed after exogenous cuing when the cue-target interval exceeds approximately 250 ms (inhibition of return [IOR]), and not after endogenous cuing. We suggest that, usually, no IOR is found with endogenous cues because no bottom-up saliency-based orienting processes are claimed. Therefore, we developed an endogenous feature-based split-cue task to allow for endogenous saliency-based orienting. IOR was observed in the saliency-driven endogenous cuing condition, and not in the control condition that prevented saliency-based orienting. These results suggest that usage of saliency-based orienting processes in either endogenous or exogenous orienting warrants the appearance of IOR. PMID- 22038668 TI - Leptomeningeal Carcinomatosis in Esophageal Cancer: Case Report and Review of Literature. PMID- 22038669 TI - Audit of management of gallbladder cancer in a Nigerian tertiary health facility. AB - BACKGROUND: Gallbladder cancer is a rare malignancy with a variable incidence worldwide. It ranks number eight among all gastrointestinal cancer seen in Nigeria. It is associated with high mortality and morbidity because it is usually diagnosed very late. Adequate surgical resection is the only modality with hope of cure. This requires advanced surgical skills which is quite rare in most developing countries like Nigeria. In this current work, we audit the management and outcome of gallbladder cancer in our hospital, highlighting peculiarity associated with our setting. PATIENTS AND METHOD: Consecutive patients managed as cases of gallbladder cancer at Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria between January 1990 and December 2010 were studied retrospectively. Patient demographics, disease and treatment-related variables, and outcomes were analyzed by SPSS version 16.0. RESULTS: Thirty-one cases of gallbladder cancer were diagnosed over the 21-year period, and this accounts for about 0.3% of all cancer cases seen in our hospital. The median age of this patient cohort was 58 years (range 28 to 79 years). Seventeen (54.8%) patients were age below 60 while 14 (45.2%) were age 60 and above. Twenty-seven patients (87.1%) were female and four (12.9%) were male, with a male to female ratio approximately 1:7. Over 80% of the patients presented with a triad of upper abdominal pain, weight loss, and jaundice. Majority (67.7%) of the patients were diagnosed intraoperatively. Only four patients underwent complete resection as they had radical cholecystectomy including regional lymph node dissection and wedge resection of the gallbladder fossa of the liver. The stages of the resected patients were T3 in three patients and T2 in one. Overall 1- and 5-year survival rates for our entire patient cohort were 32% and 10%, respectively. CONCLUSION: In conclusion, this study showed that preoperative diagnosis of gallbladder cancer could be challenging in our environment. A triad of upper abdominal pain, jaundice, and weight loss with judicious use of available radiological modality will increase the chances of making the preoperative diagnosis of the cancer. It also showed that good outcome can be obtained when radical surgery is offered to these few patients within the limitation of resources in few patients with resectable tumor. PMID- 22038670 TI - Nipple- or skin-sparing mastectomy and immediate breast reconstruction by the "moving window" operation. AB - BACKGROUND: Endoscope-assisted skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) has been developed to minimize the skin incision and to improve the cosmetic outcome of reconstructed breast for patients with breast cancer. However, this procedure can be performed without using endoscopic instruments. METHODS: We have performed SSM or NSM via a small periareolar incision with axillary incision using wound retractors without disposable endoscopic instruments. After the entire breast tissue was removed, immediate breast reconstruction (IBR) using tissue expanders was performed through the axillary incision. RESULTS: Twelve patients (13 cases: 1 patient had synchronous bilateral primary cancer) underwent NSM, and 8 had SSM because of involvement of the nipple areola complex. IBR was performed with tissue expanders in 18 patients, while 2 patients refused to have IBR because of small breast size. When 3 patients with synchronous or metachronous bilateral breast cancer were excluded, the average length of surgery was 267 min in 15 patients who underwent SSM or NSM followed by IBR with implants, while it was only 120 min in 2 patients who underwent NSM alone. Average blood loss was 135 mL (range 40-350 mL). CONCLUSION: We have described a novel technique using the wound retractor for SSM or NSM followed by IBR in treating breast cancer patients. This technique can minimize skin incisions without using disposable endoscopic instruments and improve the cosmetic outcome of the reconstructed breast. PMID- 22038671 TI - An osteogenesis imperfecta case with breast cancer. AB - Osteogenesis imperfecta (OI) is a rare connective tissue disease characterized by abnormalities of type 1 collagen and an increased risk of bone fractures. Several OI cases with malignancies have been reported. Herein, we describe an OI case with breast cancer. A 36-year-old premenopausal woman with OI was admitted to our hospital for evaluation of a right breast lump. We diagnosed right breast cancer with axillary and parasternal lymph node metastasis (T2N3M0 stage IIIC). The tumor had increased in size and tumor markers were elevated after 10 months of hormone therapy. We performed a right mastectomy and axillary dissection. She subsequently received adjuvant chemotherapy and radiotherapy. She is currently taking trastuzumab and tamoxifen. Anesthesia is challenging in OI patients because of difficulty with airway control and intubation. We performed the mastectomy in this case without difficulty by working in cooperation with experienced anesthesiologists, orthopedists, and other medical personnel. Some OI patients reportedly have severe 5-fluorouracil (5-FU) toxicity related to dihydropyrimidine dehydrogenase (DPD) deficiency. DPD is the main enzyme involved in the catabolism of 5-FU. Our present case also had low DPD activity and we thus chose epirubicin and cyclophosphamide for chemotherapy. Our search of the literature yielded only two OI cases with breast cancer as of April 2011. To our knowledge, this is the first case reported in Japan. PMID- 22038672 TI - Paradigm shift in axilla surgery for breast cancer patients treated with sentinel node biopsy. AB - BACKGROUND: Sentinel node biopsy (SNB) is a standard technique for the diagnosis of regional lymph node metastases in clinically node-negative breast cancer patients. In the case of pathologically negative sentinel lymph nodes (SLN), axillary lymph node dissection (ALND) can be avoided. METHODS: Recent clinical studies on SNB in breast cancer were reviewed regarding the pathological and molecular diagnosis of SLN, the tools used to predict non-SLN metastases, the prognostic significance of isolated tumor cells (ITC) and micrometastases (MIC), and axilla surgery. RESULTS: ITC or MIC in SLN was associated with worse survival in patients treated with SNB alone or SNB followed by ALND. However, this effect was limited and adjuvant therapy improved survival. If T1 and one SLN-positive breast cancer patients are treated with whole-breast irradiation and adjuvant therapy, additional ALND may not be necessary. CONCLUSIONS: SNB without ALND can be adopted for patients with a small number of SLN metastases. Although the lack of apparent regional lymph node recurrence, similar to tumor dormancy, cannot be fully explained, ALND should be performed in cases that are highly suspected to be non-SLN metastases. PMID- 22038673 TI - Microfluidic devices with disposable enzyme electrode for electrochemical monitoring of glucose concentrations. AB - This article describes the fabrication of tube-like microchannels made of UV curable polymer on a glass substrate and the device assembling with a disposable enzyme-working electrode for high-sensitivity electrochemical detection. While both reference and counter electrodes are patterned on the surface of the glass substrate, the working electrode is flipped on the top of the channel with an open access, providing a face-to-face probing configuration. When the enzyme electrode is contaminated or degraded, it can be easily replaced by a new one, keeping the main body of the device and the detection schema unchanged. Using glucose oxidase-coated gold electrodes, we were able to determine a linear amperometry response to the glucose concentrations in the range of 2-16 mM. By replacing the as-prepared working electrode by the one after thermal treatments, we showed a much more degraded enzyme electrode activity, enabling efficient determination of the electrode quality as well as the whole process optimization. PMID- 22038675 TI - Systematic review of psychosocial morbidities among bereaved parents of children with cancer. AB - The objective of this review was to comprehensively summarize existing studies utilizing validated instruments to measure psychosocial outcomes among bereaved parents of children with cancer. This population has increased risks of anxiety, depression, prolonged grief, and poor quality of life. Parental morbidity is associated with psychiatric co-morbidities, prior loss, economic hardship, duration, and intensity of child's cancer-therapy, perceptions of medical care, child's quality of life, preparedness for and location of the child's death. Rigorous, prospective research is needed to identify risk-groups, define outcomes, and design interventions which will improve parental outcomes after the death of a child due to cancer. PMID- 22038674 TI - Demographic correlates of DSM-IV major depressive disorder among older African Americans, Black Caribbeans, and non-Hispanic Whites: results from the National Survey of American Life. AB - OBJECTIVES: To examine the demographic correlates of lifetime and 12-month prevalence of major depressive disorder (MDD) among older African Americans, Black Caribbeans, and non-Hispanic Whites. METHODS: Data are from adults aged 55 years and older (n = 1439) recruited to the National Survey of American Life (NSAL; 2001-2003). The Diagnostic and Statistical Manual Version IV World Mental Health Composite International Diagnostic Interview was used to assess the 12 month and lifetime MDD. Weighted logistic regression was used to model demographic correlates of MDD. RESULTS: The population prevalence of lifetime and 12-month MDD were 11.2% and 4.1%, respectively. Bivariate analyses revealed that younger respondents and those with greater disability had a higher prevalence of both lifetime and 12-month MDD compared with those who were older and who had lower disability. Multivariable logistic regressions controlling for demographic characteristics revealed that non-Hispanic Whites had the greatest odds of lifetime MDD (OR = 2.27, 95% CI = 1.32, 3.93). Women had significantly greater odds of lifetime MDD compared with men (OR = 2.49, 95% CI = 1.14, 5.41); there were no gender differences in 12-month MDD. Other significant predictors of MDD were marital status and region of residence. CONCLUSIONS: The distribution, correlates, and nature of associations with MDD vary as a function of whether we examined lifetime vs. 12-month MDD. Future work should account for within group differences among older adults with depression. Understanding MDD correlates and the nature of intergroup diversity can inform the identification of particularly vulnerable subgroups as well as appropriate treatment approaches. PMID- 22038676 TI - Cyclic thrombocytopenia associated with marked rebound thrombocytosis and fluctuating levels of endogenous thrombopoietin and reticulated platelets: a case report. PMID- 22038678 TI - Compound toxicity screening and structure-activity relationship modeling in Escherichia coli. AB - Synthetic biology and metabolic engineering are used to develop new strategies for producing valuable compounds ranging from therapeutics to biofuels in engineered microorganisms. When developing methods for high-titer production cells, toxicity is an important element to consider. Indeed the production rate can be limited due to toxic intermediates or accumulation of byproducts of the heterologous biosynthetic pathway of interest. Conversely, highly toxic molecules are desired when designing antimicrobials. Compound toxicity in bacteria plays a major role in metabolic engineering as well as in the development of new antibacterial agents. Here, we screened a diversified chemical library of 166 compounds for toxicity in Escherichia coli. The dataset was built using a clustering algorithm maximizing the chemical diversity in the library. The resulting assay data was used to develop a toxicity predictor that we used to assess the toxicity of metabolites throughout the metabolome. This new tool for predicting toxicity can thus be used for fine-tuning heterologous expression and can be integrated in a computational-framework for metabolic pathway design. Many structure-activity relationship tools have been developed for toxicology studies in eukaryotes [Valerio (2009), Toxicol Appl Pharmacol, 241(3): 356-370], however, to the best of our knowledge we present here the first E. coli toxicity prediction web server based on QSAR models (EcoliTox server: http://www.issb.genopole.fr/~faulon/EcoliTox.php). PMID- 22038679 TI - A chronological history of the International Conference on Cryptococcus and Cryptococcosis (ICCC), an invaluable forum for growth of the cryptococcal research field and clinical practice. AB - Cryptococcologists meet every 3 years to present their new research data and discuss the current state of cryptococcosis therapy at the International Conference on Cryptococcus and Cryptococcosis (ICCC). The ICCC has served as a unique forum where mycologists could interact and share their research data in a setting exclusively devoted to the study of Cryptococcus and cryptococcosis. This article presents an historical perspective on the ICCC meetings, beginning with the first ICCC that was held in Jerusalem, Israel in 1989. Subsequent ICCC meetings have grown, in terms of attendance and submitted abstracts. The history of the ICCC serves as a testimony to the remarkable progress that has been made in our basic understanding of the molecular biology, biochemistry, ecology, and taxonomy of Cryptococcus as well as the epidemiology, immunology, clinical manifestations, and treatment for cryptococcosis. PMID- 22038677 TI - Primary immunodeficiency diseases associated with neurologic manifestations. AB - Primary immunodeficiency diseases (PID) are a heterogeneous group of inherited disorders of the immune system, predisposing individuals to recurrent infections, allergy, autoimmunity, and malignancies. A considerable number of these conditions have been found to be also associated with neurologic signs and symptoms. These manifestations are considered core features of some immunodeficiency syndromes, such as ataxia-telangiectasia and purine nucleoside phosphorylase deficiency, or occur less prominently in some others. Diverse pathological mechanisms including defective responses to DNA damage, metabolic errors, and autoimmune phenomena have been associated with neurologic abnormalities; however, several issues remain to be elucidated. Greater awareness of these associated features and gaining a better understanding of the contributing mechanisms will lead to prompt diagnosis and treatment and possibly development of novel preventive and therapeutic strategies. In this review, we aim to provide a brief description of the clinical and genetic characteristics of PID associated with neurologic complications. PMID- 22038680 TI - Rectal balloon training as add-on therapy to pelvic floor muscle training in adults with fecal incontinence: a randomized controlled trial. AB - AIMS: Fecal incontinence (FI) is embarrassing, resulting in poor quality of life. Rectal sensation may be more important than sphincter strength to relieve symptoms. A single-blind, randomized controlled trial among adults with FI compared the effectiveness of rectal balloon training (RBT) and pelvic floor muscle training (PFMT) versus PFMT alone. METHODS: We randomized 80 patients, recruited from the Maastricht University Medical Centre. Primary outcome was based on the Vaizey score. Secondary outcomes were the Fecal Incontinence Quality of Life Scale (FIQL), 9-point global perceived effect (GPE) score, anorectal manometry, rectal distension volumes, and thresholds of anorectal sensation. Analyses were by intention-to-treat. RESULTS: Forty patients were assigned to combined RBT with PFMT and 40 to PFMT alone. Adding RBT did not result in a significant improvement in the Vaizey score [mean difference: -1.19; 95% confidence interval (CI): -3.79 to 1.42; P = 0.37]. Secondary outcomes favoring RBT were: Lifestyle subscale of the FIQL (0.37; 95% CI: 0.02-0.73; P = 0.04), GPE (-1.01; 95% CI: -1.75 to -0.27; P = 0.008), maximum tolerable volume (49.35; 95% CI: 13.26-85.44; P = 0.009), and external anal sphincter fatigue (0.65; 95% CI: 0.26-1.04; P = 0.001). Overall, 50% of patients were considered improved according to the estimated minimally important change (Vaizey change >=-5). CONCLUSIONS: RBT with PFMT was equally effective as PFMT alone. Secondary outcomes show beneficial effects of RBT on urgency control, GPE, and lifestyle adaptations. Characteristics of patients who benefit most from RBT remain to be confirmed. PMID- 22038681 TI - Suboptimal responses in chronic myeloid leukemia: implications and management strategies. AB - The high response rates and increased survival associated with imatinib therapy prompted a paradigm shift in the management of chronic myeloid leukemia. However, 25% to 30% of imatinib-treated patients develop drug resistance or intolerance, increasing the risk of disease progression and poor prognosis. In 2006, the European LeukemiaNet proposed criteria to identify patients with a suboptimal response to, or failure associated with, imatinib; these recommendations were updated in 2009. Suboptimal responders represent a unique treatment challenge. Although they may respond to continued imatinib therapy, their long-term outcomes may not be as favorable as those for optimally responding patients. Validation studies demonstrated that suboptimal responders are a heterogeneous group, and that the prognostic implications of suboptimal response vary by time point. There are few data derived from clinical trials to guide therapeutic decisions for these patients. Clinical trials are currently underway to assess the efficacy of newer tyrosine kinase inhibitors in this setting. Identification of suboptimal responders or patients failing treatment using hematologic, cytogenetic, and molecular techniques allows physicians to alter therapy earlier in the treatment course to improve long-term outcomes. PMID- 22038682 TI - Asymmetric synthesis of chiral 1,3-diaminopropanols: bisoxazolidine-catalyzed C-C bond formation with alpha-keto amides. PMID- 22038684 TI - Docosahexaenoic acid: a natural powerful adjuvant that improves efficacy for anticancer treatment with no adverse effects. AB - Epidemiological studies have linked fish oil consumption to a decreased incidence of cancer. The anticancer effects of fish oil are mostly attributed to its content of omega-3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, DHA, because of its unique effect of altering membrane composition, is often regarded as the major omega-3 fatty acid involved in anticancer activity. Although use of DHA as an anticancer drug to prevent or treat human cancer in clinical settings has not yet been well established, recent studies suggest that DHA can be very effective as an adjuvant with other anticancer agents. In this article, we present studies that show the role of DHA in improving anticancer drug efficacy. Several in vitro and animal studies suggest that combining DHA with other anticancer agents often improves efficacy of anticancer drugs and also reduces therapy-associated side effects. Incorporation of DHA in cellular membranes improves drug uptake, whereas increased lipid peroxidation is another mechanism for DHA-mediated enhanced efficacy of anticancer drugs. In addition, several intracellular targets including cyclooxygenase-2, nuclear factor kappa B, peroxisome proliferator activated receptor gamma, mitogen-activated protein kinase, AKT, and BCL-2/BAX are found to play an important role in DHA-mediated additive or synergistic interaction with anticancer drugs. The data suggest that DHA is a safe, natural compound that can greatly improve the anticancer properties of anticancer drugs. Use of DHA with anticancer treatments provides an avenue to therapeutic improvement that involves less risk or side effects for patients and reduced regulatory burden for implementation. PMID- 22038683 TI - Restless legs syndrome: a comprehensive overview on its epidemiology, risk factors, and treatment. AB - PURPOSES: Restless legs syndrome (RLS) is underdiagnosed and poorly understood by clinicians and the general public alike; accordingly, a broad literature review with information most relevant to general practice is needed to help dispel misconceptions and improve level of care. METHODS: Specifically, this review comprehensively provides an epidemiological analysis of RLS and examines the risk factors and treatment options for RLS by compiling the findings of past RLS studies. These RLS studies were identified through a retrospective PubMed search. The epidemiological analysis was conducted by calculating a weighted mean average of all the relevant general population RLS prevalence studies, separated into geographical/racial categories. RESULTS: A comprehensive analysis of RLS epidemiological studies finds the prevalence rate of RLS to be 5-15% in the general population with 2.5% of adults having symptoms severe enough to require medical intervention. Some of the risk factors for RLS include female gender, pregnancy, low iron levels, lower socioeconomic status, poor health, elderly age, comorbidity with Parkinson's disease, positive family history of RLS, and comorbidity with psychiatric disorders. A wide array of treatment options exist for RLS including pharmacological and nonpharmacologic interventions. CONCLUSIONS: Clinicians' understanding of RLS enigma has recently improved due to the increased intensity of RLS research over the past decade. This review summarizes the current findings in the RLS field as well as providing guidelines for future RLS-related research. PMID- 22038685 TI - Influence of side chain length on fluorescence intensity of ROMP-based polymeric nanoparticles and their tumor specificity in in-vivo tumor imaging. AB - In this study, amphiphilic brush-like copolymers conjugated with short alkyl or long polymeric chains of various lengths are synthesized using ring-opening metathesis polymerization (ROMP) of substituted norbornadiene monomers followed by chemical transformations. These amphiphilic copolymers form spherical self assemblies in aqueous media with diameters of 132-244 nm. The low critical aggregation concentration of these assemblies (2.5 * 10(-3) -1.4 * 10(-5) g/L) indicates that they are quite stable in dilute conditions. An appropriate length of polymer side chain that conjugates the polymer backbone with a hydrophobic ICG (indocyanine green) moiety enhanced the fluorescence intensities of these self assemblies in aqueous solution as well as in tumor-bearing mice. A longer side chain conjugated with tumor targeting agents could significantly affect the tumor specificity of self-assemblies to a greater extent. The self-assemblies bearing hydrophilic tumor targeting agents, such as a glucosamine molecule and a cyclic RGD (arginine-glycine-asparatic acid) peptide, accumulated in tumor tissues with high selectivity, while those having a hydrophobic targeting agent, such as folate moieties, accumulated in tumor sites with low selectivity. The results demonstrated here unambiguously indicate that the fluorescence intensity and tumor specificity of self-assemblies are strongly affected by the length of side chains that conjugate with dyes and targeting agents. PMID- 22038686 TI - Identification of C18 intermediates formed during stearidonic acid biohydrogenation by rumen microorganisms in vitro. AB - In vitro batch incubations were used to study the rumen biohydrogenation of unsaturated fatty acids. An earlier study using increasing supplementation levels of stearidonic acid (18:4n-3), revealed that the rumen microbial population extensively biohydrogenates 18:4n-3 after 72 h of in vitro incubation, though several intermediates formed were not completely characterized. Therefore, in the present study, samples were reanalyzed in order to identify the 18:2, 18:3 and 18:4 biohydrogenation intermediates of 18:4n-3. Gas-liquid chromatography coupled to mass spectrometry was used to characterize these intermediates. The acetonitrile chemical ionization mass spectrometry of the fatty acid methyl esters derivatives enabled the discrimination of fatty acids as non-conjugated or conjugated biohydrogenation intermediates. In addition, the acetonitrile covalent adduct chemical ionization tandem mass spectrometry yielded prominent ions indicative of the double bond position of the major 18:3 isomers, i.e. Delta5,11,15 18:3. Furthermore, the 4,4-dimethyloxazoline derivatives prepared from the fatty acid methyl esters enabled the structure of novel 18:2, 18:3 and 18:4 biohydrogenation intermediates to be elucidated. The intermediates accumulated in the fermentation media after 72 h of incubation of 18:4n-3 suggest that similar to the biohydrogenation pathways of linoleic (18:2n-6) and alpha linolenic (18:3n-3) acids, the pathway of the 18:4n-3 also proceeds with the formation of conjugated fatty acids followed by hydrogenation, although no conjugated dienes were found. The formation of the novel biohydrogenation intermediates of 18:4n-3 seems to follow an uncommon isomerization pattern with distinct double bond migrations. PMID- 22038688 TI - Microcrustaceans escape behavior as an early bioindicator of copper, chromium and endosulfan toxicity. AB - The purpose of this work was to experimentally analyze the impact of copper, chromium and a commercial pesticide with endosulfan on the escape behavior of two copepods (Notodiaptomus conifer, Argyrodiaptomus falcifer) and three cladocerans (Daphnia magna, Pseudosida variabilis and Ceriodaphnia dubia). The experimental assays were carried out using a novel hydraulic devise designed to mimic three speed predator capture behavior. Two concentrations, one "high" and one "low", were employed and the exposure time was 15 (+/-5) minutes. With two exceptions, the species exposed to heavy metals manifested higher ability to escape than controls. Both concentrations of the pesticide reduced the escape ability of cladocerans but copepods responded, in general, in a similar manner as for heavy metals. The immediate apparent advantage of low and early toxic effects is discussed and the high sensitivity of the escape behavior suggests that it could be a complementary endpoint to be used in future ecotoxicological tests. PMID- 22038687 TI - Niemann-Pick C2 protein expression regulates lithogenic diet-induced gallstone formation and dietary cholesterol metabolism in mice. AB - Niemann-Pick C2 protein (NPC2) is a lysosomal soluble protein that is highly expressed in the liver; it binds to cholesterol and is involved in intracellular cholesterol trafficking, allowing the exit of lysosomal cholesterol obtained via the lipoprotein endocytic pathway. Thus, this protein may play an important role in controlling hepatic cholesterol transport and metabolism. The aim of this work was to study the relevance of NPC2 protein expression in hepatic cholesterol metabolism, biliary lipid secretion and gallstone formation by comparing NPC2 hypomorph [NPC2 (h/h)] and wild-type mice fed control, 2% cholesterol, and lithogenic diets. NPC2 (h/h) mice exhibited resistance to a diet-induced increase in plasma cholesterol levels. When consuming the chow diet, we observed increased biliary cholesterol and phospholipid secretions in NPC2 (h/h) mice. When fed the 2% cholesterol diet, NPC2 (h/h) mice exhibited low and high gallbladder bile cholesterol and phospholipid concentrations, respectively. NPC2 (h/h) mice fed with the lithogenic diet showed reduced biliary cholesterol secretion, gallbladder bile cholesterol saturation, and cholesterol crystal and gallstone formation. This work indicates that hepatic NPC2 expression is an important factor in the regulation of diet-derived cholesterol metabolism and disposal as well as in diet-induced cholesterol gallstone formation in mice. PMID- 22038689 TI - Homeostatic regulation of elemental stoichiometry by Lemna gibba L. G3 when nutrient interact with toxic metals. AB - We investigated responses of Lemna gibba L. to exposure to UO(2)(2+) and AsO(4)(3 ) under variable PO(4)(3-) concentration. Total plant phosphorus (P(tot)) in L. gibba and accumulation of dissolved organic carbon (DOC) in the media were quantified and tested for correlation with plant yield and initial concentrations of PO(4)(3-), UO(2)(2+) and AsO(4)(3-). The accumulation of DOC in medium was high under low PO(4)(3-) supply and increased loading of either UO(2)(2+) or AsO(4)(3-). The P(tot) was low in high initial concentration of UO(2)(2+) and AsO(4)(3-) as well under acute low PO(4)(3-) supply. The DOC accumulation correlated negatively to the P(tot). This reveals interaction between PO(4)(3-) and UO(2)(2+) or AsO(4)(3-) in the medium interferes with the uptake process of PO(4) (3-). Hence, the DOC accumulation is exudation of low molecular weight organic substance by L. gibba in response to the reduced P(tot): biomass ratio (carbon in the yield) due to delimited acquisition of phosphorus from the medium. It is a homeostatic regulation of the stoichiometry, which is disturbed during the interaction between PO(4)(3-) and UO(2)(2+) or AsO(4)(3-). Further investigations are necessary to relate these interactions to traditional resource stoichiometry elements of C, N, and P. PMID- 22038690 TI - Molecular design to improve the performance of donor-pi acceptor near-IR organic dye-sensitized solar cells. PMID- 22038691 TI - Intronic tandem repeat in the serotonin transporter gene in Old World monkeys: a new transcriptional regulator? AB - The serotonin transporter gene (SLC6A4) is heavily involved in the regulation of social behaviour of primates. Old World monkeys (e.g. macaques, baboons) have been used to study interactions between variation in the SLC6A4 gene and behaviour. Correlations of variation at one polymorphism located in the promoter region (known as 5HTTLPR) and variation at SLC6A4 expression levels, serotonin turnover and behaviour has been widely studied. In Old World monkeys, the third intron of the SLC6A4 gene also presents a tandem repeat, which sequence varies across species by a few point substitutions. We predict that in these species, this repeated region also acts as transcriptional regulatory domain and that sequence variation at this polymorphic locus might result in differential levels of expression in gene-environment interactions. For testing these hypotheses, the tandem repeat of Mandrillus sphinx and Cercopithecus aethiops from the third intron were cloned into a reporter gene vector and delivered to either primary cultures of rat neonate frontal cortex or the human cell line (JAr) to analyse their transcriptional activities. These repeated sequences supported significantly different levels of gene expression only when delivered into frontal cortex cultures. Furthermore, we tested in silico if such substitutions could have an effect on their binding profile to RNA- and DNA-binding proteins and on splicing. Taken together our results suggest that the tandem repeat in the third intron of the SLC6A4 gene of Old World monkeys could constitute a second transcriptional regulator as suggested for the 5HTTLPR and therefore contribute to diversification of serotonin-related behaviour in these primates. PMID- 22038692 TI - MRT letter: Contrast-enhanced computed tomographic imaging of soft callus formation in fracture healing. AB - Formation of a cartilaginous soft callus at the site of a bone fracture is a pivotal stage in the healing process. Noninvasive, or even nondestructive, imaging of soft callus formation can be an important tool in experimental and pre clinical studies of fracture repair. However, the low X-ray attenuation of cartilage renders the soft callus nearly invisible in radiographs. This study utilized a recently developed, cationic, iodinated contrast agent in conjunction with micro-computed tomography to identify cartilage in fracture calluses in the femora of C57BL/6J and C3H/HeJ mice. Fracture calluses were scanned before and after incubation in the contrast agent. The set of pre-incubation images was registered against and then subtracted from the set of post-incubation images, resulting in a three-dimensional map of the locations of cartilage in the callus, as labeled by the contrast agent. This map was then compared to histology from a previous study. The results showed that the locations where the contrast agent collected in relatively high concentrations were similar to those of the cartilage. The contrast agent also identified a significant difference between the two strains of mice in the percentage of the callus occupied by cartilage, indicating that this method of contrast-enhanced computed tomography may be an effective technique for nondestructive, early evaluation of fracture healing. PMID- 22038693 TI - Posterior fossa syndrome in an adult patient following surgical evacuation of an intracerebellar haematoma. AB - The posterior fossa syndrome (PFS) consists of transient cerebellar mutism, cognitive symptoms and neurobehavioural abnormalities that typically develop in children following posterior fossa tumour resection. Although PFS has been documented in more than 350 paediatric cases, reports of adult patients with a vascular aetiology are extremely rare. In addition, the pathophysiological substrate of the syndrome remains unclear. We report an adult patient with PFS after surgical evacuation of a cerebellar bleeding. After 45 days of (akinetic) mutism, the patient's cognitive and behavioural profile closely resembled the "cerebellar cognitive-affective syndrome". A quantified SPECT study showed perfusional deficits in the anatomoclinically suspected supratentorial areas, subserving language dynamics, executive functioning, spatial cognition and affective regulation. We hypothesize that cerebello-cerebral diaschisis might be an important pathophysiological mechanism underlying akinetic mutism, cognitive deficits and behavioural-affective changes in adult patients with PFS. PMID- 22038694 TI - Fabrication optimization of a miniaturized array device for cell-free protein synthesis. AB - Cell-free protein synthesis (CFPS) is an attractive alternative to cell-based protein expression systems because of its advantages including speed, simplicity, and adaptability to various formats. However, two major obstacles exist that have been preventing it from being widely used. One is high cost and the other is low protein synthesis yield. We report here a miniaturized CFPS device that addresses these challenges. The cost saving was achieved by miniaturization, which reduced the reagent consumption by two orders of magnitude. The protein synthesis yield was enhanced by prolonging CFPS reactions through continuous supply of reactants (e.g. nutrients and energy components). The reactants were contained in a feeding solution, which was replenished through a nanoporous membrane and microchannel. The design of the miniaturized device was optimized by running continuous exchange CFPS in devices with a variation in the type of membrane, the size of the exchange interface, and the volume ratio of the reaction solution to the feeding solution. The effects of these design variations on the protein synthesis yield have been studied. Furthermore, the design was expanded into a 96-unit device that can produce a large number of proteins simultaneously, enabling high throughput proteomics applications. PMID- 22038696 TI - The limits of narrative: provocations for the medical humanities. AB - This paper aims to (re)ignite debate about the role of narrative in the medical humanities. It begins with a critical review of the ways in which narrative has been mobilised by humanities and social science scholars to understand the experience of health and illness. I highlight seven dangers or blind spots in the dominant medical humanities approach to narrative, including the frequently unexamined assumption that all human beings are 'naturally narrative'. I then explore this assumption further through an analysis of philosopher Galen Strawson's influential article 'Against Narrativity'. Strawson rejects the descriptive claim that "human beings typically see or live or experience their lives as a narrative" and the normative claim that "a richly Narrative outlook is essential to a well-lived life, to true or full personhood". His work has been taken up across a range of disciplines, but its implications in the context of health and illness have not yet been sufficiently discussed. This article argues that 'Against Narrativity' can and should stimulate robust debate within the medical humanities regarding the limits of narrative, and concludes by discussing a range of possibilities for venturing 'beyond narrative'. PMID- 22038697 TI - The linear interaction energy method for the prediction of protein stability changes upon mutation. AB - The coupling of protein energetics and sequence changes is a critical aspect of computational protein design, as well as for the understanding of protein evolution, human disease, and drug resistance. To study the molecular basis for this coupling, computational tools must be sufficiently accurate and computationally inexpensive enough to handle large amounts of sequence data. We have developed a computational approach based on the linear interaction energy (LIE) approximation to predict the changes in the free-energy of the native state induced by a single mutation. This approach was applied to a set of 822 mutations in 10 proteins which resulted in an average unsigned error of 0.82 kcal/mol and a correlation coefficient of 0.72 between the calculated and experimental DeltaDeltaG values. The method is able to accurately identify destabilizing hot spot mutations; however, it has difficulty in distinguishing between stabilizing and destabilizing mutations because of the distribution of stability changes for the set of mutations used to parameterize the model. In addition, the model also performs quite well in initial tests on a small set of double mutations. On the basis of these promising results, we can begin to examine the relationship between protein stability and fitness, correlated mutations, and drug resistance. PMID- 22038698 TI - Risk-adapted therapy for infantile myofibromatosis in children. AB - BACKGROUND: Infantile myofibromatosis is characterized by proliferation of benign fibrous tumors arising in skin, subcutaneous tissue, muscle, or bone. Solitary and multicentric forms are described. Few reports are available in the pediatric population. PROCEDURE: To improve the knowledge of this rare tumor in infants, the authors present a series of all cases of infantile myofibromatosis treated in their institution over a 9-year period in order to propose treatment guidelines based on their experience and a review of the literature. RESULTS: The authors report a series of 9 cases, 8 solitary forms and 1 multicentric form with visceral involvement treated from 2000 to 2009. Median age was 10 months (range: 2 days-14 years). Six patients with solitary forms underwent primary surgical resection leading to remission. Only biopsy was performed in 1 case, followed by tumor regression with no recurrence. The last patient with a solitary form was treated by chemotherapy and then surgery allowing remission. The patient with a multicentric form presented complete regression of tumors after 1 year of vinblastine and methotrexate combination chemotherapy. CONCLUSIONS: Infantile myofibromatosis is a rare soft tissue tumor mainly concerning infants. Surgery is the treatment of choice for solitary forms when excision is possible. Close follow-up may be proposed in the case of inoperable sites. In multicentric life threatening forms, chemotherapy promotes tumor regression and the vinblastine and methotrexate combination is effective with few long-term adverse effects. PMID- 22038700 TI - Synergistic palladium-catalyzed C(sp3)-H activation/C(sp3)-O bond formation: a direct, step-economical route to benzolactones. PMID- 22038699 TI - Cytochrome c dissolved in 1-allyl-3-methylimidazolium chloride type ionic liquid undergoes a quasi-reversible redox reaction up to 140 degrees C. AB - Solubility of cytochrome c, a typical heme protein, in a various ionic liquids has been analyzed. The solubility has been discussed with polarity parameters of the ionic liquids. Both hydrogen bond basicity and dipolarity/polarizability of the ionic liquids were confirmed to be influential factors to control the solubilization of cytochrome c. Polar ionic liquids such as 1-butyl-3 methylimidazolium chloride and 1-allyl-3-methylimidazolium chloride solubilized cytochrome c at 80 degrees C, and the dissolved cytochrome c was found to keep its redox activity in these ionic liquids. The redox response of the dissolved cytochrome c was detected in 1-allyl-3-methylimidazolium chloride up to 140 degrees C. PMID- 22038701 TI - Myeloid neoplasms with isolated isochromosome 17q represent a clinicopathologic entity associated with myelodysplastic/myeloproliferative features, a high risk of leukemic transformation, and wild-type TP53. AB - BACKGROUND: Isolated isochromosome (17q) is a rare cytogenetic abnormality in Philadelphia chromosome-negative myeloid neoplasms, usually myelodysplastic and/or myeloproliferative neoplasms (MDS/MPN). De novo acute myeloid leukemia (AML) with isochromosome 17q has rarely been reported. The frequency of genetic mutations is unknown. METHODS: The authors assessed clinicopathologic, immunophenotypic, and molecular genetic features of 22 myeloid neoplasms with isolated isochromosome 17q. RESULTS: Fourteen patients presented as MDS/MPN; 8 as de novo AML. Most presented with leukocytosis, anemia, thrombocytopenia, and splenomegaly. Morphologically, all showed myelodysplastic and myeloproliferative features, including pseudo-Pelger-Huet-like neutrophils, micromegakaryocytic hyperplasia, hypercellularity, fibrosis, and osteosclerosis. Blasts were increased (median, 40% in de novo AML; 9% in MDS/MPN). Immunohistochemical assessment of proliferation and apoptosis rates in AML were similar to a matched group without isochromosome 17q. In most patients, isochromosome 17q occurred at time of blast transformation or disease progression. DNA sequencing revealed no mutation in the uninvolved TP53 allele. Mutational analyses showed rare mutations in NRAS (3 of 10), FLT3 (2 of 16), and JAK2 (1 of 18), and no mutations in NPM1 (0 of 15), KIT (0 of 4), and CEBPA (0 of 4). The median overall survival was 14.5 months for de novo AML, and 11.0 months for MDS/MPN. With a median follow-up of 8.5 months (range, 1.5-107 months), 15 died of disease, 6 had persistent disease, and 1 was in remission after bone marrow transplantation. CONCLUSIONS: The authors conclude that myeloid neoplasms with isolated isochromosome 17q represent a distinct clinicopathologic entity with myelodysplastic and myeloproliferative features, high risk of leukemic transformation, and wild-type TP53. PMID- 22038702 TI - Is HbA2 level a reliable diagnostic measurement for beta-thalassemia trait in people with iron deficiency? PMID- 22038703 TI - A real-world study of patients with type 2 diabetes initiating basal insulins via disposable pens. AB - INTRODUCTION: Real-world data comparing outcomes of type 2 diabetes mellitus (T2DM) patients initiating different insulin regimens can help with treatment decisions and patient management. Clinical and economic outcomes following initiation with insulin glargine disposable pen (GLA-P) or insulin detemir disposable pen (DET-P) in T2DM patients were compared over 1-year follow-up. METHODS: This retrospective cohort analysis was conducted on data in a US national managed care claims database (July 2006 to September 2010) from patients initiating insulin treatment with GLA-P or DET-P. Treatment persistence, adherence, glycated hemoglobin (A1C), hypoglycemic events, and healthcare costs during follow-up were compared. RESULTS: In all, 1682 patients were identified; 1016 (60.4%) started using GLA-P, 666 (39.6%) started using DET-P. After 1:1 propensity score matching, each cohort comprised 640 patients. Patients initiating GLA-P were significantly more likely to persist and adhere to treatment, and used a lower daily consumption dose. Over the last quarter of follow-up, fewer GLA-P users switched to DET-P compared with those switching from DET-P to GLA-P. GLA-P was associated with lower A1C levels and higher reduction of A1C levels from baseline, with no significant difference in the number of patients having hypoglycemic events. Patients in both cohorts had similar total and diabetes-related healthcare costs, but healthcare costs were lower in the GLA P cohort for each 1% reduction in A1C from baseline. CONCLUSION: This real-world study demonstrates that patients initiating GLA-P were more likely to persist with and adhere to treatment, with better glycemic control and similar overall hypoglycemia rate at no increase in healthcare cost. PMID- 22038704 TI - Electrophysiological correlates of exemplar-specific processes in implicit and explicit memory. AB - The present ERP study investigated the retrieval of task-irrelevant exemplar specific information under implicit and explicit memory conditions. Subjects completed either an indirect memory test (a natural/artificial judgment) or a direct recognition memory test. Both test groups were presented with new items, identical repetitions, and perceptually different but conceptually similar exemplars of previously seen study objects. Implicit and explicit memory retrieval elicited clearly dissociable ERP components that were differentially affected by exemplar changes from study to test. In the indirect test, identical repetitions, but not different exemplars, elicited a significant ERP repetition priming effect. In contrast, both types of repeated objects gave rise to a reliable old/new effect in the direct test. The results corroborate that implicit and explicit memory fall back on distinct cognitive representation and, more importantly, indicate that these representations differ in the type of stimulus information stored. Implicit retrieval entailed obligatory access to exemplar specific perceptual information, despite its being task irrelevant. In contrast, explicit retrieval proved to be more flexible with conceptual and perceptual information accessed according to task demands. PMID- 22038705 TI - Social deviance activates the brain's error-monitoring system. AB - Social psychologists have long noted the tendency for human behavior to conform to social group norms. This study examined whether feedback indicating that participants had deviated from group norms would elicit a neural signal previously shown to be elicited by errors and monetary losses. While electroencephalograms were recorded, participants (N = 30) rated the attractiveness of 120 faces and received feedback giving the purported average rating made by a group of peers. The feedback was manipulated so that group ratings either were the same as a participant's rating or deviated by 1, 2, or 3 points. Feedback indicating deviance from the group norm elicited a feedback related negativity, a brainwave signal known to be elicited by objective performance errors and losses. The results imply that the brain treats deviance from social norms as an error. PMID- 22038706 TI - Authenticity affects the recognition of emotions in speech: behavioral and fMRI evidence. AB - The aim of the present study was to determine how authenticity of emotion expression in speech modulates activity in the neuronal substrates involved in emotion recognition. Within an fMRI paradigm, participants judged either the authenticity (authentic or play acted) or emotional content (anger, fear, joy, or sadness) of recordings of spontaneous emotions and reenactments by professional actors. When contrasting between task types, active judgment of authenticity, more than active judgment of emotion, indicated potential involvement of the theory of mind (ToM) network (medial prefrontal cortex, temporoparietal cortex, retrosplenium) as well as areas involved in working memory and decision making (BA 47). Subsequently, trials with authentic recordings were contrasted with those of reenactments to determine the modulatory effects of authenticity. Authentic recordings were found to enhance activity in part of the ToM network (medial prefrontal cortex). This effect of authenticity suggests that individuals integrate recollections of their own experiences more for judgments involving authentic stimuli than for those involving play-acted stimuli. The behavioral and functional results show that authenticity of emotional prosody is an important property influencing human responses to such stimuli, with implications for studies using play-acted emotions. PMID- 22038707 TI - Integration of microchip electrophoresis with electrochemical detection using an epoxy-based molding method to embed multiple electrode materials. AB - This paper describes the use of epoxy-encapsulated electrodes to integrate microchip-based electrophoresis with electrochemical detection. Devices with various electrode combinations can easily be developed. This includes a palladium decoupler with a downstream working electrode material of either gold, mercury/gold, platinum, glassy carbon, or a carbon fiber bundle. Additional device components such as the platinum wires for the electrophoresis separation and the counter electrode for detection can also be integrated into the epoxy base. The effect of the decoupler configuration was studied in terms of the separation performance, detector noise, and the ability to analyze samples of a high ionic strength. The ability of both glassy carbon and carbon fiber bundle electrodes to analyze a complex mixture was demonstrated. It was also shown that a PDMS-based valving microchip can be used along with the epoxy-embedded electrodes to integrate microdialysis sampling with microchip electrophoresis and electrochemical detection, with the microdialysis tubing also being embedded in the epoxy substrate. This approach enables one to vary the detection electrode material as desired in a manner where the electrodes can be polished and modified as is done with electrochemical flow cells used in liquid chromatography. PMID- 22038708 TI - Temporal and spatial expression of CCN3 during retina development. AB - NOV/CCN3 is one of the founding members of the CCN (Cyr61 CTGF NOV) family. In the avian retina, CCN3 expression is mostly located within the central region of the inner nuclear layer. As retinal development progresses and this retinal layer differentiates and matures, CCN3 expression forms a dorsal-ventral and a central peripheral gradient. CCN3 is produced by two glial cell types, peripapillary cells and Muller cells, as well as by horizontal, amacrine, and bipolar interneurons. In retinal neurons and Muller cell cultures, CCN3 expression is induced by activated BMP signaling, whereas Notch signaling decreases CCN3 mRNA and protein levels in Muller cells and has no effect in retinal neurons. In Muller cells, the CCN3 expression detected may thus result from a balance between the Notch and BMP signaling pathways. PMID- 22038709 TI - High dose trans-10,cis-12 CLA increases lean body mass in hamsters, but elevates levels of plasma lipids and liver enzyme biomarkers. AB - The current study examined the efficacy of graded doses of c9,t11 and t10,c12 CLA isomers on body composition, energy expenditure, hepatic and serum lipid liver biomarkers in hamsters. Animals (n = 105) were randomized to seven treatments (control, 1, 2, 3% of c9,t11; 1, 2, 3% of t10,c12) for 28 days. After 28 days treatment, 1-3% of t10,c12 lowered (p < 0.05) body fat mass compared to the control group. The 1-3% t10,c12 and 3% c9,t11 fed groups showed higher (p < 0.05) lean mass compared to other groups. We observed unfavorable changes in plasma total cholesterol and non-HDL cholesterol levels in animals fed with 3% t10,c12 CLA isomers. The 2%, 3% t10,c12 groups presented elevated (p < 0.05) ALT levels. The present data suggest that a diet enriched with more than 2% t10, c12 led to liver malfunction and poses unfavorable changes on plasma lipid profiles. The 1% t10,c12 CLA lowered (p < 0.05) body fat mass and increased (p < 0.05) lean body mass. The c9,t11 CLA has less potent actions than t10,c12 CLA. We conclude that the actions of CLA on energy and lipid metabolism are form and dose dependent in the hamster model. PMID- 22038710 TI - Effect of oral intake of winged bean extract on a skin lichenification model: evaluation by microarray analysis. AB - Winged bean (WB), Psophocarpus tetragonolobus, is a tropical legume, the potential of which is not fully understood. We found that 5-week oral administration of a WB seed extract inhibited wrinkle formation induced by repeated tape stripping (TS) as a model of lichenification in human chronic eczematous dermatitis. To elucidate the mechanism of the effect of WB on this model, we applied microarray analysis. Hierarchical clustering revealed that each experimental group formed a distinct cluster, suggesting the presence of a distinct gene expression profile among the three groups of non-TS, TS, and TS with oral administration of WB extract (TS/WB). Gene ontology analysis showed that several gene groups with keratinization and mitosis were significantly upregulated by TS, while other groups with ATP synthesis and glycolysis were significantly downregulated by TS/WB. Moreover, WB extract influenced a number of genes related to epidermal differentiation and inflammation. This suggests that these changes inhibited wrinkle formation by TS. PMID- 22038711 TI - Thermally stable AgI quantum-dot-based room-temperature fast ionic conductors. AB - AgI quantum dot (QD)-based room-temperature fast ionic conductors are prepared via an aqueous route. New phase behavior and good performance are found in this material. This is a prototype of quantum dot-ionics. PMID- 22038712 TI - Two classes of movements in motor control. AB - This work investigated whether fundamental differences emerged between segments of complex movement sequences performed at different instructed speeds. To this end, we tested 5 novices and 1 karate expert as they performed beginner's martial arts routines. We found that if one blindly took these segments and separated them according to the variability of trajectory parameters, one could unambiguously group two classes of movements between the same two space regions: one type that remained quite conserved despite speed changes and another type that changed with speed level. These groups corresponded to functionally different movements (strike segments explicitly directed to a set of goals and spontaneously retracting segments supplementing the goals). The curvature of the goal-directed segments remained quite conserved despite speed changes, yet the supplemental movements spanned families of trajectories with different curvature according to the speed. Likewise, the values of the hand's peak velocity across trials were more variable in supplemental segments, and for each participant, there were different statistical signatures of variability between the two movement classes. This dichotomy between coexisting movement classes of our natural actions calls for a theoretical characterization. The present experimental results strongly suggest that two separate sets of principles may govern these movement classes in complex natural behaviors, since under different dynamics the hand did not describe a unique family of trajectories between the same two points in the 3D space. PMID- 22038713 TI - Cortical responses to the mirror box illusion: a high-resolution EEG study. AB - The mirror box illusion has proven a helpful therapy in pathologies such as phantom limb pain, and although the effect has been suggested to be a result of the interaction between pain, vision, touch, and proprioception, the mechanisms are still unknown. Multichannel (124) brain responses were investigated in healthy men (N = 11) and women (N = 14) during the mirror box illusion. Tactile somatosensory evoked potentials were recorded from the right thumb during two control conditions and two illusions: (control 1) no mirror: looking at the physical right thumb during stimulation, (control 2) no mirror: looking at the physical left thumb during stimulation, (illusion 1) mirror: the illusion that both thumbs were stimulated, and (illusion 2) mirror: the illusion that none of the thumbs were stimulated. In men, a significant medial shift in the y coordinate of the N70 dipole in illusion 2 (P = 0.021) was found when compared with illusion 1. No dipole shift was found for women. Additionally, men showed higher prevalence of P180 cingulate cortex activation during illusion 2 when compared with control 1 and 2 (P = 0.002). During illusion 2, the degree of conformity with the statement "The hand in the mirror feels like my other hand" was negatively correlated with the N70 x coordinate for men and positively correlated with the N70 z coordinate for women. In conclusion, short-term cortical plasticity can be induced by a mismatch between visual input and location of tactile stimulation in men. The present study suggests that gender differences exist in the perception of the mirror box illusion. PMID- 22038714 TI - Dissociation of brain areas associated with force production and stabilization during manipulation of unstable objects. AB - Multifinger dexterous manipulation of unstable or deformable objects requires control of both direction and magnitude of fingertip force vectors. Our aim was to study the neuroanatomical correlates of these two distinct control functions. Brain activity was measured using functional magnetic resonance imaging while 16 male subjects (age: 26-42, M = 32, SD +/- 4 years) compressed four springs representing a 2 * 2 factorial design with two levels of force and instability requirements. Significant activations associated with higher instability were located bilaterally in the precentral gyri, the postcentral gyrus, and the cerebellum. In the main effect for high force, activity was found in areas located in the primary motor regions contralateral to the active hand and bilaterally in the cerebellum. An overlap in activation between the two main effects was found bilaterally in the cerebellum (lobule VI). This study not only confirms a recently described bilateral fronto-parieto-cerebellar network for manipulation of increasingly unstable objects, but critically extends our understanding by describing its differentiated modulation with both force magnitude and instability requirements. Our results, therefore, expose a previously unrecognized and context-sensitive system of brain regions that enable dexterous manipulation for different force magnitude and instability requirements of the task. PMID- 22038716 TI - Post-exercise depression in corticomotor excitability after dynamic movement: a general property of fatiguing and non-fatiguing exercise. AB - Transcranial magnetic stimulation has been used to study changes in central excitability associated with motor tasks. Recently, we reported that a finger flexion-extension task performed at a maximal voluntary rate (MVR) could not be sustained and that this was not due to muscle fatigue, but was more likely a breakdown in central motor control. To determine the central changes that accompany this type of movement task, we tracked motor-evoked potential (MEP) amplitude from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles of the dominant hand in normal subjects for 20 min after a 10 sec index finger flexion-extension task performed at MVR and at a moderate sustainable rate (MSR) and half the MSR (MSR(/2)). The FDI MEP amplitude was reduced for up to 6-8 min after each of the tasks but there was a greater and longer-lasting reduction after the MSR and MSR(/2) tasks compared to the MVR task. There was a similar reduction in the amplitude of the FDI MEP after a 10 sec cyclic index finger abduction-adduction task when the FDI was acting as the prime mover. The amplitude of the MEP recorded from the inactive APB was also reduced after the flexion-extension tasks, but to a lesser degree and for a shorter duration. Measurements of short-interval cortical inhibition revealed an increase in inhibition after all of the finger flexion-extension tasks, with the MSR task being associated with the greatest degree of inhibition. These findings indicate that a demanding MVR finger movement task is followed by a period of reduced corticomotor excitability and increased intracortical inhibition. However, these changes also occur with and are greater with slower rates of movement and are not specific for motor demand, but may be indicative of adaptive changes in the central motor pathway after a period of repetitive movement. PMID- 22038715 TI - Caenorhabditis elegans as a model organism to study APP function. AB - The brains of Alzheimer's disease patients show an increased number of senile plaques compared with normal patients. The major component of the plaques is the beta-amyloid peptide, a cleavage product of the amyloid precursor protein (APP). Although the processing of APP has been well-described, the physiological functions of APP and its cleavage products remain unclear. This article reviews the multifunctional roles of an APP orthologue, the C. elegans APL-1. Understanding the function of APL-1 may provide insights into the functions and signaling pathways of human APP. In addition, the physiological effects of introducing human beta-amyloid peptide into C. elegans are also reviewed. The C. elegans system provides a powerful genetic model to identify genes regulating the molecular mechanisms underlying intracellular beta-amyloid peptide accumulation. PMID- 22038717 TI - Continuation tapping to triggered melodies: motor resonance effects of melodic motion. AB - Common Coding theory predicts that perceived action should resonate in produced action to which it bears some resemblance. Here we show that the qualities of motion commonly attributed to melodies are instantiated in motor plans that control timed movements. Participants attempted to tap a steady beat. Each tap triggered a sounded tone, and successive tones were systematically varied in pitch to form short melodies. Tapping behavior was monitored with motion capture. Although instructed to ignore them, triggered tones systematically affected timing and finger movement. When slower melodic motion was implied by a contour change or a smaller pitch displacement, the interval-tap interval (ITI) was longer. When faster melodic motion was implied by a preserved pitch contour or a larger pitch displacement, ITI was shorter. Kinematic recordings suggested that ITI Error arose from an initial failure to disambiguate perception (i.e., velocity implied by melodic motion) from action (i.e., finger velocity [FV]). Early in the tap trajectory, slower FV was associated with longer ITI and faster FV was associated with shorter ITI. These associations were reversed near mid trajectory, suggesting a transition from execution of motor planning to online control (Glover et al. in Exp Brain Res 154:103-108, 2004). PMID- 22038719 TI - Motor synergies for dampening hand vibration during human walking. AB - This study investigated the motion required to carry a cup filled with water without spilling it, which is a common human dexterous task. This task requires the individual to dampen hand vibration while walking. We hypothesize that a reduction in hand jerk and a constant cup angle are required to achieve this task. We measured movements while human subjects carried a cup with water (WW task) and with stones (WS task) using a three-dimensional position measurement system and then analyzed joint coordination. We empirically confirmed that the value of hand jerk and the variance in cup angle in the WW task were smaller than those in the WS task. We used uncontrolled manifold (UCM) analysis to quantify joint coordination corresponding to the motor synergy required to reduce the hand jerk and variance of the cup angle. UCM components, which did not affect the hand jerk and cup angle, were larger than orthogonal components, which directly affected the hand jerk and cup angle in the WW task. These results suggest that there is a coordinated control mechanism that reduces hand jerk and maintains a constant cup angle when carrying a cup filled with water without spilling it. In addition, we suggest that humans adopt a flexible and coordinated control strategy of allowing variance independent of the variables that should be controlled to achieve this dexterous task. PMID- 22038718 TI - Multiple neural representations of object-directed action in an imitative context. AB - Object-directed action consists of aspects that range from low-level kinematic patterns to high-level action goals. Although previous studies have suggested that the human mirror neuron system (MNS) is involved in understanding or imitating an observed action, it is unclear precisely which levels of action representation are reflected in MNS activity. In this study, we used an imitation matching task, which is previously used in behavioral experiments for infants, and fMRI to reveal the neural basis for imitation of multiple representations of observed actions. In our experiment, two video footages showing a pen being grasped and placed into one of two cups were sequentially presented. The participants judged whether an actor's action in the first movie was correctly imitated by an imitator in the second movie, regarding the following four aspects: action goal, a means of manipulation, an effector used, and movement trajectory. Although identical sets of stimuli were presented, different brain regions were activated, depending on the matching judgments made by subjects between the two actions. The current study indicates that distinct brain regions are involved in recognition of multiple aspects of transitive actions, which is largely consistent with a visuomotor circuit of action production by the observer. PMID- 22038720 TI - Importance of binocular vision in foot placement accuracy when stepping onto a floor-based target during gait initiation. AB - This study investigated the importance of binocular vision to foot placement accuracy when stepping onto a floor-based target during gait initiation. Starting from stationary, participants placed alternate feet onto targets sequentially positioned along a straight travel path with the added constraint that the initial target (target 1) could move in the medio-lateral (M-L) direction. Repeated trials when target 1 remained stationary or moved laterally at the instant of lead-limb toe-off (TO) or 200 ms after TO (early swing) were undertaken under binocular and monocular viewing. Catch trials when target 1 shifted medially were also undertaken. Foot-reach kinematics, foot trajectory corrections and foot placement accuracy for the step onto target 1 were determined via 3D motion analyses. Peak foot-reach velocity and initial foot reach duration were unaffected by vision condition but terminal foot-reach duration was prolonged under monocular conditions (p = 0.002). Foot trajectory alteration onsets were unaffected by vision condition, but onsets occurred sooner when the target shifted in early swing compared to at TO (p = 0.033). M-L foot placement accuracy decreased (p = 0.025) and variability increased (p = 0.05) under monocular conditions, particularly when stepping onto the moving target. There was no difference between vision conditions in A-P foot placement accuracy. Results indicate that monocular vision provides sufficient information to determine stepping distance and correctly transport the foot towards the target but binocular vision is required to attain a precise M-L foot placement; particularly so when stepping onto a moving target. These findings are in agreement with those found in the reaching and grasping literature, indicating that binocular vision is important for end-point precision. PMID- 22038721 TI - Getting a grip on illusions: replicating Stottinger et al [Exp Brain Res (2010) 202:79-88] results with 3-D objects. AB - Studies using visual illusions to demonstrate a dissociation within the visual system can provide relevant and decisive data only if certain methodological points are taken into account. Although, our previous work (Stottinger et al. in Exp Brain Res 202:88-97, 2010) followed these points, the task made use of only 2 D stimuli which may raise doubts concerning the nature of grasping in that experiment. We therefore replicated the study using a 3-D version of the empty space illusion. Consistent with the earlier study, that used 2-D stimuli, we found that grip aperture followed actual target size independent of illusory effects, while perceived length, as indicated by finger-thumb span, clearly was subject to the illusion. Therefore, the prior results cannot be due to the use of 2-D stimuli. Together, these two studies provide clear evidence for the perception versus action hypothesis. PMID- 22038722 TI - Expression of high-molecular-mass neurofilament protein in horse (Equus caballus) spinal ganglion neurons. AB - Spinal ganglion (SG) neurons are subdivided, on the basis of their cytoplasmic aspect at light and electron microscopy, into dark (D) and light (L) neurons. Numerous efforts have been made to find specific markers able to identify D and L neuronal cytotypes. The isolectin B4 (IB4), utilized to identify nonpeptidergic D neurons in mice, unfortunately, has not proved as effective in other species. The 200-kDa neurofilament protein (NF200) is considered as a typical marker of L neurons in the rat, cat, and chick. The aim of this study was to analyze the histological, morphometric, and neurochemical characteristic of NF200 immunoreactive (IR) horse SG neurons, to better characterize them morphologically and functionally. NF200-IR neurons showed two levels (strong and weak) of staining intensity. Most (84%) strongly stained NF200-IR neurons corresponded to L neurons, and showed similar bimodality as in the size distribution study, which seems to indicate a third population of neurons, in addition to the two populations (small and large) previously identified. In triple-staining experiments where NF200 was colocalized with IB4, substance P (SP), and neuronal nitric oxide synthase (nNOS) neuronal markers, most NF200-IR neurons were single stained. On the contrary, most IB4-, SP-, and nNOS-stained neurons were triple labeled and almost equally subdivided between strong and weak NF200-IR with the latter being always smaller in size than strong NF200-IR neurons. In conclusion, horse SG neurons display significant morphometric and neurochemical differences compared with those of rodents. PMID- 22038723 TI - Clinicopathological significance and prognostic value of Xeroderma pigmentosum complementary group C (XPC) expression in sporadic breast cancer patients. AB - Breast cancer is the most common type of cancer among women worldwide, and the incidence of breast cancer is increasing in the developing world. Estrogen exposure is a major risk factor for breast cancer, and estrogen oxidative metabolites have been implicated in chemical carcinogenesis. Xeroderma pigmentosum complementary group C (XPC) plays an important and multifaceted role in cell protection from oxidative DNA damage. Thus, XPC inactivation may be involved in the early stage of breast cancer. The aim of this study was to investigate the expression of XPC protein in sporadic breast cancer tissues and determine whether XPC expression influences breast cancer malignancy and clinical outcome. Fifteen cases of adjacent non-tumor breast tissue, 28 cases of fibroadenomas and 235 cases of breast carcinomas were examined by immunohistochemistry using polyclonal antibody to XPC. Both cytoplasmic and nuclear expression level of XPC were downregulated in breast carcinoma when compared to non-tumor tissues (P < 0.05). The nuclear expression level of XPC was significantly associated with expression of BCL2 (r = 0.231, P = 0.033) and p53 (r = 0.205, P = 0.011), and nuclear expression of XPC was significantly associated with patients' age (P = 0.024). Neither cytoplasmic nor nuclear expression level of XPC had impact on patients' survival in the whole samples. However, XPC expression was correlated with adverse survival in HER2-positive, but not HER2-negative, tumors, as demonstrated by Kaplan-Meier analysis. Our results suggested that the XPC protein is involved in the occurrence and progression of breast cancer. PMID- 22038724 TI - Analysis of the specific pathways and networks of prostate cancer for gene expression profiles in the Chinese population. AB - The global physiological function of specifically expressed genes of prostate cancer in Chinese patients is unclear. This study aims to determine the genome wide expression of genes related to prostate cancer in the Chinese population. Genes that were differentially expressed in prostate cancer were identified using DNA microarray technology. Expressions were validated by using real-time PCR. The identified genes were analyzed using the ingenuity pathway analysis (IPA) to investigate the gene ontology, functional pathway and network. A total of 1,444 genes (Fold time >= 1.5; P <= 0.05) were differentially expressed in prostate primary tumor tissue compared with benign tissue. IPA revealed a unique landscape where inductions of certain pathways were involved in Cell Cycle Regulation and proliferation. Network analysis not only confirmed that protein interactions lead to the deregulation of DNA Replication, Recombination and Repair, Cellular Compromise and Cell Cycle, Genetic Disorders and Connective Tissue Disorders, but it was also observed that many of the genes regulated by Myc contributed to the modulation of lipid Metabolism and Nucleic Acid Metabolism. Both pathway and network analysis exhibited some remarkable characteristics of prostate cancer for Chinese patients, which showed profound differences from that of other non Chinese populations. These differences may provide new insights into the molecular cascade of prostate cancer that occurs in Chinese patients. PMID- 22038725 TI - Characterization of ABL exon 7 deletion by molecular genetic and bioinformatic methods reveals no association with imatinib resistance in chronic myeloid leukemia. AB - In chronic myeloid leukemia (CML), the best characterized imatinib resistance mechanisms are BCR-ABL tyrosine kinase domain mutations and clonal evolution, but recently alternative splicing of BCR-ABL was also proposed as a mechanism for imatinib resistance. Among recently reported BCR-ABL splice variants, exon 7 deletion (Deltaexon7) was characterized in this study. The frequency of Deltaexon7 was investigated in 30 healthy controls and in 76 CML patients at different time points of the disease course by four different molecular genetic methods (direct sequencing, fragment analysis, allele-specific and quantitative PCR). The functionality and viability of the variant protein was tested by bioinformatic prediction. The Deltaexon7 was abundantly detected with similar frequency in healthy controls, in imatinib naive and resistant CML patients on BCR-ABL and also on the nontranslocated ABL. The detection rate of Deltaexon7 (varying between 17 and 100%) was highly dependent on the expression levels of BCR-ABL or ABL and the sensitivity of detection method. According to secondary structure prediction by bioinformatic methods, the exon 7 deleted mRNA is a target for nonsense-mediated decay, and the translated protein is likely to be nonfunctional and unstable. Taken together all the above observations, we concluded that Deltaexon7 is a common splice variant not associating with imatinib resistance. PMID- 22038726 TI - Angioimmunoblastic T-cell lymphoma: the effect of initial treatment and microvascular density in 31 patients. AB - The objectives of this study are to explore the clinical features and treatment outcomes and to investigate the correlation between microvessel density (MVD) and survival in patients with angioimmunoblastic T-cell lymphoma (AITL). We retrospectively analyzed clinical and follow-up data of 31 patients treated in two hospitals during 1995-2009 histologically proven AITL. We also assessed MVD in the lump of 31 previously untreated patients using alpha-CD34 immunohistochemical staining. The median age of the 31 patients was 48 years, eighty percent of the patients were in an advanced stage. 67.7% of them had B symptoms, with the follow-up of 2-13 years, the 5-year overall survival rate was 25.8%. The response rates (RR) of CHOP group and COP (cyclophosphamide, vincristine and prednisolone) group are 76.5 and 75%, respectively, which is no significant difference (P=0.894). RR did not differ whether chemotherapy regimens contained anthracycline or not. The 3-year PFS rate for patients who received COP and CHOP regimen was 25.4 and 35.3% (P=0.562), while 5-year OS rates were 25.0 and 29.4%, respectively (P=0.667). The median PFS for patients with high MVD and low MVD were 15.1 and 30.0 months (P=0.048), while the median OS were 20 and 45 months, respectively (P=0.038). Patients who were sensitive to initial chemotherapy COP regimen have the similar therapeutic effect to CHOP regimen. Patients with high MVD measured in the microenvironment had worse PFS and OS than AITL patients with low expression. PMID- 22038727 TI - Compensatory and non-compensatory effects on protein expression following BCL-2 suppression by antisense oligonucleotides. AB - Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting growth regulatory proteins. In LNCaP cells, we evaluated both monospecific and bispecific oligos that targeted and comparably suppressed the expression of bcl-2, an apoptosis inhibitory protein. Cells compensated with both suppressed caspase-3 (an apoptosis promoter) activity, and an enhancement of both androgen receptor (AR) and p300 expression. This suggests that a progression to increased androgen sensitivity accompanies bcl-2 suppression, in this tumor line. To further evaluate mechanisms of adaptation, we now evaluate the effects upon the expression of insulin-like growth factor (IGF1) and another AR coactivator, IL-4, thought to increase prostate cancer growth. IGF1 expression was not significantly altered suggesting this pathway need not be regulated when bcl-2 directed gene therapy is employed. In contrast to increased AR and p300 expression that compensated for bcl-2 suppression, the AR coactivator IL-4 expression was not increased, suggesting no role in any increased androgen sensitivity. PMID- 22038728 TI - The early addition of arsenic trioxide versus high-dose arabinoside is more effective and safe as consolidation chemotherapy for risk-tailored patients with acute promyelocytic leukemia: multicenter experience. AB - The purpose of the study was to evaluate event-free survival (EFS), overall survival (OS) and safety for early addition of arsenic trioxide (As(2)O(3)) as frontline consolidation therapy compared to high-dose arabinoside (HiDAC) in adult patients with de novo acute promyelocytic leukemia (APL). 271 patients (aged 17-65 years) received consolidation therapy containing As(2)O(3) (two 21 day courses) or HiDAC regimen. EFS at 5 years was 75% versus 54% (P < 0.001), and OS at 5 years was 83% versus 71% (P = 0.002) in As(2)O(3) and HiDAC treatment arms. 139 patients treated with As(2)O(3), EFS at 5 years reached 79% versus 56% (P = 0.014), but OS at 5 years was 77% versus 84% (P = 0.32) in low-risk (WBC <= 10 * 10(9)/L) and high-risk (WBC > 10 * 10(9)/L) cohorts. Further, patients treated with As(2)O(3) rarely incurred agranulocytosis (1.4%, P < 0.001), or severe infection (0.7%, P < 0.001). It is still very well tolerated compared to HiDAC. We confirmed that As(2)O(3) as a first-line consolidation regimen provided significant benefits of OS to patients with APL. The As(2)O(3) regimen made low risk patients gain more EFS benefits than high-risk group. The high-risk cohort receiving As(2)O(3) overcame the negative impact, yielding OS similar to that for with the low-risk patients treated with As(2)O(3). PMID- 22038729 TI - Bladder mechanoreceptor changes after artificial bladder outlet obstruction in the anesthetized rat. AB - AIMS: Experimental animal models of bladder outlet obstruction (BOO) have reproduced several features of BOO in man, i.e., detrusor hypertrophy, instability, frequency, and residual urine. This study was focused on the mechanisms underlying the development of residual urine in patient with benign prostatic hyperplasia (BPH) by examining changes in tension sensitivity of bladder mechanoreceptors in rat model. METHODS: Female adult Sprague-Dawley rats including 12 BOO and 17 sham operated rats were used in this study. Cystometrograms together with the bladder afferent activity were recorded. Tension sensitivity of the afferents was determined by plotting the normalized afferent response against the contraction evoked bladder pressure at different volumes. Degree of obstruction was assessed by the wet weight of the bladder at the end of the experiment. RESULTS: The bladder weight, maximal bladder capacity, micturition threshold volume, peak contraction force, and volume at peak contraction force were all significantly increased in obstructed animals. The threshold volume for afferent activation was increased (mean 0.60 ml compared to 0.15 ml in controls; P < 0.001), positively correlated with the bladder weight (r = 0.74). The tension sensitivity of the bladder mechanoreceptors and the slope of their normalized pressure-response functions were significantly lower at the comparable volumes in the obstructed animals. CONCLUSIONS: Rats with BOO had bladder mechanoreceptors with higher threshold volumes and lower tension sensitivity. Such changes would result in a weaker afferent drive of the micturition reflex. Similar changes may contribute to the development of residual urine and retention in patients with BOO. PMID- 22038730 TI - Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases. AB - BACKGROUND: Pediatric venous thromboembolism (VTE) is an increasingly common problem. We hypothesized that VTE occurs most commonly in tertiary care settings and that the pattern of associated illnesses may have changed from earlier reports. METHODS: The Kids' Inpatient Database 2006 was utilized to identify children <= 18 years old with in-hospital VTE. Children were identified by the presence of thrombosis specific ICD-9-CM diagnosis or procedure codes. Remaining ICD-9-CM codes were utilized to categorize patients by acute or chronic illness. The incidence of in-hospital VTE by hospital type, age, gender, race, and disposition were estimated. RESULTS: Over 4,500 children met the inclusion criteria (188/100,000 discharges). Most VTE discharges (67.5%) were from children's hospitals (RR 5.09; 95% CI 4.76; 5.44). Underlying chronic illnesses were associated with most VTE (76.2%), most commonly: cardiovascular (18.4%), malignancy (15.7%), and neuromuscular disease (9.9%). VTE not associated with chronic illness were most often idiopathic (12.6%), followed by infections (9.5%), and trauma (9.1%). The greatest proportions of children with VTE were infants (23.1%) and adolescents (37.8%). However, when standardized against the entire database of discharges, infants were least likely to develop VTE (RR 0.48; 95% CI 0.43; 0.52), while adolescents were at highest risk (RR 1.89; 95% CI 1.73; 2.07). Hospitalizations ending with death were more likely to include VTE (RR 6.16; 95% CI 5.32; 7.13). CONCLUSIONS: Pediatric VTE is most commonly seen in tertiary care. Adolescents are at greatest risk to develop in-hospital VTE. Patients whose hospitalization ended with death are at much greater risk to develop VTE. PMID- 22038731 TI - PresCont: predicting protein-protein interfaces utilizing four residue properties. AB - An important task of computational biology is to identify those parts of a polypeptide chain, which are involved in interactions with other proteins. For this purpose, we have developed the program PresCont, which predicts in a robust manner amino acids that constitute protein-protein interfaces (PPIs). PresCont reaches state-of-the-art classification quality on the basis of only four residue properties that can be readily deduced from the 3D structure of an individual protein and a multiple sequence alignment (MSA) composed of homologs. The core of PresCont is a support vector machine, which assesses solvent-accessible surface area, hydrophobicity, conservation, and the local environment of each amino acid on the protein surface. For training and performance testing, we compiled three nonoverlapping datasets consisting of permanently formed or transient complexes, respectively. A comparison with SPPIDER, ProMate, and meta-PPISP showed that PresCont compares favorably with these highly sophisticated programs, and that its prediction quality is less dependent on the type of protein complex being considered. This balance is due to a mutual compensation of classification weaknesses observed for individual properties: For PPIs of permanent complexes, solvent-accessible surface and hydrophobicity contribute most to classification quality, for PPIs of transient complexes, the assessment of the local environment is most significant. Moreover, we show that for permanent complexes a segmentation of PPIs into core and rim residues has only a moderate influence on prediction quality. PresCont is available as a web service at http://www bioinf.uni-regensburg.de/. PMID- 22038732 TI - Enhanced recovery of antitumor ganoderic acid T from Ganoderma lucidum mycelia by novel chemical conversion strategy. AB - The removal of analog impurities with a very small sample size presents a major challenge in the purification of high-valued biochemicals such as those derived from fermentation or herbs. Ganoderic acid T (GA-T), an antitumor drug candidate, is very difficult to purify from the mycelia of medicinal mushroom Ganoderma lucidum due to co-purifying analog impurities. A novel pretreatment process with three consecutive chemical conversion steps, namely hydrolysis-acetylation hydrolysis, was developed to convert two key analog impurities (7-O-ethyl GA-O and GA-Mk) to GA-T. It increased the GA-T amount in the 100 g dried mycelia from the initial 0.444 g to 1.621 g after the pretreatment, representing an apparent yield of 365% for the pretreatment. If the yield basis were the initial GA-T amount plus the GA-T amount from 100% conversion of 7-O-ethyl GA-O and GA-Mk in the crude extract, the yield, termed adjusted yield for the pretreatment in this work, would still reach 90.8%. Furthermore, the subsequent RP-HPLC purification was considerably enhanced due to the conversion of the analog impurities. This game-changer strategy achieved a daily GA-T throughput of 2.9 g with 95% purity (mass based). Even at the laboratory scale, it is now possible to produce a sufficient amount of GA-T for small-scale pharmacological and clinical evaluations. The approach of converting analog impurities that are otherwise difficult to remove to the product in a bioseparation process may be useful to achieve enhanced recovery of other medicinally useful natural products. PMID- 22038733 TI - Unintended benefit of anabolic steroid use in hemophilia B leiden. PMID- 22038734 TI - Catalytic degenerate and nondegenerate oxygen atom transfers employing N2O and CO2 and a M(II)/M(IV) cycle mediated by Group 6 M(IV) terminal oxo complexes. PMID- 22038735 TI - A topological method for global optimization of clusters: application to (TiO2)n (n = 1-6). AB - A new topological method is presented to generate the isomer structures of compound clusters with well defined covalent bonds. This method, combined with density functional theory, has been used to perform global optimization of (TiO(2))(n) (n = 1-6) clusters. Our comprehensive search not only reproduces all of the known lowest-energy structures reported in previous works but also reveals some new low-energy structures. Some energetically unfavorable motifs that induce energy penalties are obtained and discussed. Based on the ground state structures of the anionic (TiO(2))(n). clusters, the electron affinities and photoelectron spectra are simulated and compared with available experimental data. PMID- 22038736 TI - Genetic polymorphisms in obesity-related genes and endometrial cancer risk. AB - BACKGROUND: Obesity is associated with circulating levels of adiponectin and leptin and endometrial cancer risk. Little is known about whether single nucleotide polymorphisms (SNPs) in the genes that encode adiponectin (ADIPOQ), leptin (LEP), adiponectin receptor 1 (ADIPOR1), adiponectin receptor 2 (ADIPOR2), and leptin receptor (LEPR) are associated with endometrial cancer. METHODS: The authors selected 87 tagging SNPs to capture common genetic variants in these 5 genes. These SNPs were evaluated in 1028 endometrial cancer cases and 1932 community controls recruited from Chinese women. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Three of the 10 SNPs evaluated in the ADIPOQ gene were significantly associated with reduced cancer risk. The OR for women homozygous for the minor allele (A/A) for rs3774262 was 0.68 (95% CI, 0.48-0.97) compared with women homozygous for the major allele (G/G). Similar results were found for SNPs rs1063539 and rs12629945 in ADIPOQ, which were in linkage disequilibrium with rs3774262. These associations became nonsignificant after Bonferroni correction was applied. Controls with the minor allele A at rs3774262 had lower weight, smaller waist and hip circumferences, and lower body mass index than controls with the major allele G (all P < .05). Women homozygous for the minor allele (T/T) of rs2071045 in the LEP gene also had significantly lower risk (OR, 0.70; 95% CI, 0.54-0.90) than women homozygous for the major allele (C/C). No other SNPs in the LEP, ADIPOR1, ADIPOR2, or LEPR genes were found to be associated with cancer risk. CONCLUSIONS: Although a chance finding cannot be ruled out, the consistency of findings for gene-endometrial cancer risk and gene-obesity measurements suggests that genetic polymorphisms in the ADIPOQ gene may play a role in endometrial cancer development. PMID- 22038737 TI - Differential reinforcement and resistance to change of divided-attention performance. AB - Behavioral momentum theory provides a framework for understanding how conditions of reinforcement influence instrumental response strength under conditions of disruption (i.e., resistance to change). The present experiment examined resistance to change of divided-attention performance when different overall probabilities of reinforcement were arranged across two components of a multiple schedule. Pigeons responded in a delayed-matching-to-sample procedure with compound samples (color + line orientation) and element comparisons (two colors or two line orientations). Reinforcement ratios of 1:9, 1:1, and 9:1 for accurate matches on the two types of comparison trials were examined across conditions using reinforcement probabilities (color/lines) of .9/.1, .5/.5, and .1/.9 in the rich component and .18/.02, .1/.1, and .02/.18 in the lean component. Relative accuracy with color and line comparisons was an orderly function of relative reinforcement, but this relation did not depend on the overall rate of reinforcement between components. The resistance to change of divided-attention performance was greater for both trial types in the rich component with presession feeding and extinction, but not with decreases in sample duration. These findings suggest promise for the applicability of quantitative models of operant behavior to divided-attention performance, but they highlight the need to further explore conditions impacting the resistance to change of attending. PMID- 22038738 TI - Human nonverbal discrimination of relative and absolute number. AB - The nonverbal discrimination of relative and absolute number of sequential visual stimuli was investigated with humans in bisection, reproduction, and report tasks. Participants viewed a sequence of 40 red and black objects on each trial, randomly intermixed, and had to identify the number of red objects, which varied from 1 to 20. To prevent the use of a verbal-counting strategy, participants were required to name the objects as they appeared. The characteristics of human performance resembled those of pigeons in analogous procedures (Tan & Grace Learning and Behavior 38:408-417, 2010; Tan, Grace, Holland, & McLean Journal of Experimental Psychology 33:409-427, 2007): Average response number increased systematically with sample number, and bisection points were located at the arithmetic, not the geometric, mean. Additionally, in both the reproduction and report tasks, coefficients of variation decreased for values less than 6 but increased or remained constant for larger values, suggesting that different representations were used for small and large numbers. PMID- 22038739 TI - Effects of down-regulation of microRNA-23a on TNF-alpha-induced endothelial cell apoptosis through caspase-dependent pathways. AB - AIMS: Endothelial cell injury induced by inflammatory factors plays a critical role in the pathogenesis of numerous vascular diseases. MicroRNAs are well known to be implicated in cell proliferation and apoptosis in inflammatory responses; however, it remains to be determined whether microRNAs are associated with tumour necrosis factor (TNF)-alpha-mediated endothelial cell injury. The aim of the present study was to investigate the role of microRNAs in TNF-alpha-induced endothelial cell apoptosis. METHODS AND RESULTS: Microarrays were used to analyse the global expression of microRNAs in TNF-alpha-stimulated human primary endothelial cells. Expression profiles of the microRNAs were verified using qRT PCR. After TNF-alpha treatment, 12 miRNAs were dramatically up-regulated and nine were down-regulated. LNA-anti-miR-23a and pre-miR-23a were found to modulate one of the markedly down-regulated miRNAs, miR-23a, which could in turn increase or attenuate TNF-alpha-induced endothelial cell apoptosis. Bioinformatics analysis suggested that caspase-7 and serine/threonine kinase 4 are potential targets of miR-23a. LNA-anti-miR-23a enhanced but pre-miR-23a inhibited the activation of caspase-7, serine/threonine kinase 4, and its related signalling caspase-3 after TNF-alpha treatment; however, neither pre-miR-23a nor LNA-anti-miR-23a had an effect on TNF-alpha-induced Bcl-2 activation. CONCLUSION: Our results suggest that miR-23a may be involved in TNF-alpha-induced endothelial cell apoptosis through regulation of the caspase-7 and serine/threonine kinase 4-caspase-3 pathways. PMID- 22038740 TI - Role of microRNAs in the reperfused myocardium towards post-infarct remodelling. AB - Myocardial ischaemia/reperfusion (I/R)-induced remodelling generally includes cell death (necrosis and apoptosis), myocyte hypertrophy, angiogenesis, cardiac fibrosis, and myocardial dysfunction. It is becoming increasingly clear that microRNAs (miRNAs or miRs), a group of highly conserved small (~18-24 nucleotide) non-coding RNAs, fulfil specific functions in the reperfused myocardium towards post-infarct remodelling. While miR-21, -133, -150, -195, and -214 regulate cardiomyocyte hypertrophy, miR-1/-133 and miR-208 have been elucidated to influence myocardial contractile function. In addition, miR-21, -24, -133, -210, 494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis. Myocardial fibrosis can be regulated by the miR-29 family and miR-21. Moreover, miR-126 and miR-210 augment I/R-induced angiogenesis, but miR-24, -92a, and -320 suppress post-infarct neoangiogenesis. In this review, we summarize the latest advances in the identification of myocardial ischaemia-associated miRNAs and their functional significance in the modulation of I/R-triggered remodelling. Controversial effects of some miRNAs in post-infarct remodelling will be also discussed. PMID- 22038741 TI - PI3Kgamma inhibition reduces blood pressure by a vasorelaxant Akt/L-type calcium channel mechanism. AB - AIMS: The lipid and protein kinase phosphoinositide 3-kinase gamma (PI3Kgamma) is abundantly expressed in inflammatory cells and in the cardiovascular tissue. In recent years, its role in inflammation and in cardiac function and remodelling has been unravelled, highlighting the beneficial effects of its pharmacological inhibition. Furthermore, a role for PI3Kgamma in the regulation of vascular tone has been emphasized. However, the impact of this signalling in the control of blood pressure is still poorly understood. Our study investigated the effect of a selective inhibition of PI3Kgamma, obtained by using two independent small molecules, on blood pressure. Moreover, we dissected the molecular mechanisms involved in control of contraction of resistance arteries by PI3Kgamma. METHODS AND RESULTS: We showed that inhibition of PI3Kgamma reduced blood pressure in normotensive and hypertensive mice in a concentration-dependent fashion. This effect was dependent on enhanced vasodilatation, documented in vivo by decreased peripheral vascular resistance, and ex vivo by vasorelaxing effects on isolated resistance vessels. The vasorelaxation induced by PI3Kgamma inhibition relied on blunted pressure-induced Akt phosphorylation and a myogenic contractile response. Molecular insights revealed that PI3Kgamma inhibition affected smooth muscle L type calcium channel current density and calcium influx by impairing plasma membrane translocation of the alpha1C L-type calcium channel subunit responsible for channel open-state probability. CONCLUSION: Overall our findings suggest that PI3Kgamma inhibition could be a novel tool to modulate calcium influx in vascular smooth muscle cells, thus relaxing resistance arteries and lowering blood pressure. PMID- 22038742 TI - Enhanced cardiac PI3Kalpha signalling mitigates arrhythmogenic electrical remodelling in pathological hypertrophy and heart failure. AB - AIMS: Cardiac hypertrophy and heart failure are associated with QT prolongation and lethal ventricular arrhythmias resulting from decreased K(+) current densities and impaired repolarization. Recent studies in mouse models of physiological cardiac hypertrophy revealed that increased phosphoinositide-3 kinase-alpha (PI3Kalpha) signalling results in the up-regulation of K(+) channels and the normalization of ventricular repolarization. The experiments here were undertaken to test the hypothesis that increased PI3Kalpha signalling will counteract the adverse electrophysiological remodelling associated with pathological hypertrophy and heart failure. METHODS AND RESULTS: In contrast to wild-type mice, left ventricular (LV) hypertrophy, induced by transverse aortic constriction (TAC), did not result in prolongation of ventricular action potentials or QT intervals in mice with cardiac-specific expression of constitutively active PI3Kalpha (caPI3Kalpha). Indeed, repolarizing K(+) currents and K(+) channel subunit transcripts were increased in caPI3Kalpha + TAC LV myocytes in proportion to the TAC-induced cellular hypertrophy. Congestive heart failure in a transgenic model of dilated cardiomyopathy model is accompanied by prolonged QT intervals and ventricular action potentials, reduced K(+) currents and K(+) channel transcripts. Increased PI3Kalpha signalling, but not renin angiotensin system blockade, in this model also results in increased K(+) currents and improved ventricular repolarization. CONCLUSION: In the setting of pathological hypertrophy or heart failure, enhanced PI3Kalpha signalling results in the up-regulation of K(+) channel subunits, normalization of K(+) current densities and preserved ventricular function. Augmentation of PI3Kalpha signalling, therefore, may be a useful and unique strategy to protect against the increased risk of ventricular arrhythmias and sudden death associated with cardiomyopathy. PMID- 22038743 TI - Changes in Notch signaling coordinates maintenance and differentiation of the Drosophila larval optic lobe neuroepithelia. AB - A dynamic balance between stem cell maintenance and differentiation paces generation of post-mitotic progeny during normal development and maintenance of homeostasis. Recent studies show that Notch plays a key role in regulating the identity of neuroepithelial stem cells, which generate terminally differentiated neurons that populate the adult optic lobe via the intermediate progenitor cell type called neuroblast. Thus, understanding how Notch controls neuroepithelial cell maintenance and neuroblast formation will provide critical insight into the intricate regulation of stem cell function during tissue morphogenesis. Here, we showed that a low level of Notch signaling functions to maintain the neuroepithelial cell identity by suppressing the expression of pointedP1 gene through the transcriptional repressor Anterior open. Increased Notch signaling, which coincides with transient cell cycle arrest but precedes the expression of PointedP1 in cells near the medial edge of neuroepithelia, defines transitioning neuroepithelial cells that are in the process of acquiring the neuroblast identity. Transient up-regulation of Notch signaling in transitioning neuroepithelial cells decreases their sensitivity to PointedP1 and prevents them from becoming converted into neuroblasts prematurely. Down-regulation of Notch signaling combined with a high level of PointedP1 trigger a synchronous conversion from transitioning neuroepithelial cells to immature neuroblasts at the medial edge of neuroepithelia. Thus, changes in Notch signaling orchestrate a dynamic balance between maintenance and conversion of neuroepithelial cells during optic lobe neurogenesis. PMID- 22038745 TI - The age of risk: risk perception and determination following the Mental Health Act 2007. AB - Reforms to the mental health law framework for England and Wales, which were introduced by the Mental Health Act 2007, are now having a practical effect on day-to-day mental health decision-making. The 2007 Act amends the Mental Health Act 1983, which governs the compulsory hospitalisation and treatment of people with mental disorder; and represents the culmination of a protracted and controversial reform process which has spanned much of the last 15 years. One of the key foci in the 2007 Act is the question of the risk posed by the patient, primarily to others; a result of both the social and political impetus behind the reform process and mounting public anxiety at the management of the mentally disordered. The new Act seeks, as with past legislation, to find the elusive balance between protecting and facilitating the individual's autonomy while also providing an effective framework for the wider public right to protection. The 2007 Act solidifies the dominance of risk by providing a legitimating framework in which risk can be assessed, monitored, and managed. This attitudinal change is demonstrated by the gradual and almost insidious adoption of risk terminology within the practical decision-making setting and the increasing use of risk assessment and management tools. This article is informed by an empirical study which examined individual professional and institutional responses to the mental health legislation in relation to risk. It examines whether the amended legislative framework amplifies risk as an increasingly dominant concern within decision-making. The paper then goes on to consider how decision-makers use risk to assist with their daily roles. Extrapolated from data obtained through the study, several models of risk determination are then discussed. Finally, some thought is given to whether the extension of the risk concept has the potential to become more fundamental within the organisation and legitimisation of mental health care. PMID- 22038744 TI - Subtrochanteric fractures in bisphosphonate-naive patients: results from the HORIZON-recurrent fracture trial. AB - Our purpose was to characterize the risks of osteoporosis-related subtrochanteric fractures in bisphosphonate-naive individuals. Baseline characteristics of patients enrolled in the HORIZON-Recurrent Fracture Trial with a study-qualifying hip fracture were examined, comparing those who sustained incident subtrochanteric fractures with those sustaining other hip fractures. Subjects were bisphosphonate-naive or had a bisphosphonate washout period of 6-24 months and subsequently received an annual infusion of zoledronic acid 5 mg or placebo after low-trauma hip-fracture repair. In total, 2,127 men and women were included. Of the qualifying hip fractures, 5.2% were subtrochanteric, 54.8% femoral neck, 33.0% intertrochanteric, and 7.1% other (generally complex fractures of mixed type). Significant baseline (pre-hip fracture) differences were seen between index hip-fracture types, with the percentage of patients with extreme mobility problems being twofold higher in patients with index subtrochanteric fracture (9.9%) compared to other patients. The distribution of hip-fracture types was similar between the treatment groups at baseline. No patients with index subtrochanteric fractures and six patients with other qualifying hip fractures reported prior bisphosphonate use. Only one further subtrochanteric fracture occurred in each treatment group over an average 2-year patient follow-up. Subtrochanteric fractures are not uncommon in bisphosphonate naive patients. Extreme difficulties with mobility may be a unique risk factor predisposing to development of incident subtrochanteric fractures rather than other types of hip fracture. In patients with recent hip fracture who received zoledronic acid therapy, the incidence of new subtrochanteric fractures was too small to draw any meaningful conclusions. PMID- 22038746 TI - Detention and treatment down under: human rights and mental health laws in Australia and New Zealand. AB - Mental health law reform in recent decades has drawn on the international human rights movement. The entering into force of the Convention on the Rights of Persons with Disabilities (CRPD) on May 3 2008 has been hailed by some as signalling a new era in relation to how domestic mental health laws should be reformed. Both Australia and New Zealand have ratified the CRPD and Australia has acceded to its Optional Protocol. New Zealand and the Australian Capital Territory and Victoria have statutory bills of rights which have an interpretive effect, but are unable to render other statutes invalid. Drawing on the results of interviews conducted with fifty-two representatives of consumer and carer organisations, lawyers, and mental health professionals across Australia and New Zealand, this paper examines the current thinking on human rights and mental health laws in these countries and outlines what changes, if any, may be brought to domestic legislation in light of the Convention. PMID- 22038747 TI - Anti-social behaviour in a large Irish teaching hospital. AB - BACKGROUND: Anti-social behaviour affects staff physically and psychologically and has financial implications. More information on its occurrence is required for effective risk management. AIMS: We undertook to audit the complete dataset on anti-social behaviour in an urban Irish hospital. METHODS: Data, collected from computerised incident reports between January 2005 and December 2008, were analysed with respect to date, location, incident type, person affected, type and severity of injury. RESULTS: There were 3,727 incidents over 4 years, with numbers rising annually at the approximate rate of 20%. Most involved nursing staff. Incidents occurred primarily on medical and surgical wards and were usually classified as minor. Physical or verbal assaults were most frequently reported. CONCLUSION: Anti-social behaviour appears to be increasing. Certain wards and categories of healthcare professionals are at particular risk. More research is required to explain factors leading to such behaviour and optimum strategies for its active management. PMID- 22038748 TI - Guidelines reduce time to consultation for a liaison psychiatry service in an Irish teaching hospital. AB - BACKGROUND: Timeliness of response from referral to consultation is necessary to provide best standards of care to inpatients in the general hospital setting. AIMS: To measure the length of time from referral to consultation in a liaison psychiatry service, and improve service delivery by introducing guidelines for time to consultation. METHODS: Time to consultation was measured on all patients presenting to a liaison psychiatry consultation service over an initial 6-month period, with subsequent repeat measurement following the introduction of guidelines. RESULTS: There were significant reductions for time to consultation in the service for the second cycle of the audit (chi(2) = 43.84, P < 0.001), and targets based on international standards were achieved. CONCLUSIONS: Introduction of guidelines for time to consultation, may improve response times, leading to improved quality of service for inpatient consultation services. PMID- 22038749 TI - Rapid, early and sustained virological responses in a cohort of Irish patients treated with pegylated interferon and ribavirin for chronic hepatitis C virus infection. AB - BACKGROUND: The response to the treatment with pegylated interferon (PEG IFN) alpha combined with ribavirin in chronic hepatitis C virus (HCV) infection varies with some patients having a rapid or early response which is not sustained. AIMS: To investigate the rates of rapid virological response (RVR), early virological response (EVR) and sustained virological response (SVR) in an Irish cohort of HCV infected patients receiving IFN-alpha/ribavirin. METHODS: Rates of RVR, EVR and SVR were examined in 123 patients undergoing standard treatment for chronic HCV infection between 2001 and 2007 at a Dublin Teaching Hospital. RESULTS: The rates of RVR, EVR and SVR in genotype 1 patients were 48, 68 and 50%, while in genotype 2/3 patients they were 87, 93 and 87%, respectively. The positive predictive values (PPV) of RVR for SVR in genotype 1 and genotype 2/3 patients were 90 and 92.4%, respectively. CONCLUSION: The rates of response to PEG IFN alpha/ribavirin in Irish patients are consistent with other international reports. We support the regular monitoring of rapid and early virological response as a standard of care in treating chronic hepatitis C patients. PMID- 22038750 TI - Initial experience of double-layer tension free reconstruction of abdominal wall defects with porcine acellular dermal collagen implant and polypropylene mesh. AB - INTRODUCTION AND AIM: Various techniques have been proposed for the repair of abdominal wall defects (AWD) with varying rates of success. Despite the development of new materials and modifications of surgical technique, no single approach has emerged as the optimum way to close large AWD. We report a method for repairing large incisional and recurrent abdominal wall hernias using a double-mesh technique. The defect is closed using an underlay biological implant and an onlay synthetic mesh, which is 'quilted' to the underlying abdominal wall and biological implant. The current study reports our initial experience with this approach in ten consecutive patients operated on for large AWD. METHODS: In this prospective observational study the following data were collected: age, gender, previous surgery, co-morbidities, situation and size of the defect, antibiotic therapy, hospital stay, postoperative complications and bacteriology in case of infection. The patients were reviewed at 1, 3 and 6 months, and 1-year postsurgery. RESULTS: Overall all ten AWD of >= 75 cm(2) were reconstructed successfully using the quilting technique. Median age of patients was 61 years (range 47-73 years); male:female ratio was 3:2 and median weight was 107.5 kg. Two patients developed a wound infection and were treated successfully with antibiotics. At median follow-up of 15.5 months (range 6-29 months) there was no case of recurrence. CONCLUSION: The use of double-layer of porcine acellular dermal collagen implant and polypropylene mesh in reconstruction of AWD can be considered a safe and effective treatment. The early short-term results are encouraging with few complications. PMID- 22038751 TI - Insulin. PMID- 22038752 TI - An analysis of vascular surgery in elderly patients to determine whether age affects treatment strategy. AB - OBJECTIVES: The incidence of arterial disease increases with age. Increasing life expectancy in the western world will intensify demands on vascular surgeons with regard to increasing caseload, expanding patient selection criteria, and more complex and minimally-invasive treatment options. We analysed our arterial cases over the past 31 years (n = 6,144) and compared our methods of intervention and complication rates in the elderly population (>75) with the younger cohort, in order to determine whether age should influence our management strategies. METHODS: Data were collected prospectively on all arterial cases from 1978 to 2009. Methods of intervention and corresponding complication rates in the over and under 75-year-old cohorts were analyzed utilizing Fisher's exact test to calculate two-sided p values, relative risks and 95% confidence intervals. RESULTS: Endovascular management has evolved to become the first line approach for all arterial cases (except carotid disease). Age was a significant risk factor for death and MI for the open procedures of AAA repair (p = 0.049 and p = 0.007, respectively), aorto-bifemoral reconstruction (p < 0.0001 and p = 0.006) and lower limb bypass (p = 0.01 and p < 0.001). For endovascular procedures, age did not impact on MI rate for EVAR (p = 0.78) or death rates for EVAR (p = 0.46), iliac angioplasty (p = 0.62) or lower limb angioplasty (p = 0.29). CONCLUSION: A paradigm shift has occurred towards endovascular management of aortic, iliac and femoral arterial disease. Whilst patient age >75 significantly impacts on complication rates from index open vascular procedures, age does not impact upon complication rates of corresponding endovascular procedures. We, therefore, recommend an endovascular approach be adopted as first line for all patients, regardless of patient age. PMID- 22038753 TI - Results availability from clinical research of female urinary incontinence. AB - AIMS: To ascertain possible publication bias by examining the completeness and publication of studies on nonsurgical treatments for female urinary incontinence (UI). METHODS: We analyzed information about studies from several trial registries through May 2010. We searched Medline using study registration identifiers to determine publication status, and compared percentages of completed and published studies by study and subject characteristics. RESULTS: Among the 166 closed studies, we found 120 completed (73%), 12 terminated (7%), 3 withdrawn (2%), and 4 (2%) that provided no reasons for noncompletion. Only 17% of closed registered studies (28/166 studies) were published in peer-reviewed journals; publication that did occur was an average of 2.2 years after study completion. The proportion of studies published did not increase over time. Studies sponsored by industry were published less often than those funded by NIH (OR = 0.04; 95%CI: 0.004-0.38). Drug studies were published less often than studies of other interventions (OR = 0.22; 95%CI: 0.05-0.96). Of the 166 closed studies, 7 (4%) posted results on the ClinicalTrials.gov website. Of Phases III and IV trials, 7% and 3% posted results, respectively. CONCLUSIONS: The absence of results from a substantial proportion of conducted studies suggests that treatment decisions for women with UI are based on selected rather than comprehensive evidence of benefits and harms. Regulatory policy for clinical research should guarantee availability of the outcomes for the public, clinicians, and policymakers. PMID- 22038754 TI - Assembly of graphene oxide-enzyme conjugates through hydrophobic interaction. AB - Biochemical and biomedical applications of graphene oxide (GO) critically rely on the interaction of biomolecules with it. It has been previously reported that the biological activity of the GO-enzyme conjugate decreases due to electrostatic interaction between the enzymes and GO. Herein, the immobilization of horseradish peroxidase (HRP) and oxalate oxidase (OxOx) on chemically reduced graphene oxide (CRGO) are reported. The enzymes can be adsorbed onto CRGO directly with a tenfold higher enzyme loading than that on GO, and maximum enzyme loadings reach 1.3 and 12 mg mg(-1) for HRP and OxOx, respectively. Significantly, the more CRGO is reduced, the higher the enzyme loading. The CRGO-HRP conjugates also exhibit higher enzyme activity and stability than GO-HRP. Excellent properties of the CRGO-enzyme conjugates are attributed to hydrophobic interaction between the enzymes and the CRGO. The hydrophobic interaction mode of the CRGO-enzyme conjugates can be applied to other hydrophobic proteins, and thus could dramatically improve the performance of immobilized proteins. The results indicate that CRGO is a potential substrate for efficient enzyme immobilization, and is an ideal candidate as a macromolecule carrier and biosensor. PMID- 22038755 TI - MRT letter: Expression of ATP sensor protein in Caenorhabditis elegans. AB - Adenosine 5'-triphosphate (ATP) is the major energy currency and is involved in many biological processes. The ATP-monitoring system for cells in animals can be helpful to study the relationship between energy metabolism and biological processes. The fluorescent ATP biosensor ATeam (ATP indicator based on Epsilon subunit for Analytical Measurements), which has been reported to monitor ATP levels in cultured cells on the basis of fluorescence resonance energy transfer (FRET), was introduced into nematodes by microinjection and UV-irradiation method. To confirm whether ATeam functions as an ATP sensor in nematode cells, the authors measured FRET of ATeam in cells of transgenic nematode. The ATeam was expressed in target cells in nematode. In vulva cells, ATP levels in the cytosol were higher than those in mitochondria. ATeam also sensed ATP level change in cultured cells from the transgenic nematode. These experiments indicated that ATeam is available for detection of changes in ATP levels in nematode cells. PMID- 22038757 TI - Mild isolated craniosynostosis due to a novel FGFR3 mutation, p.Ala334Thr. AB - Craniosynostosis is the premature fusion of one or more sutures of the skull, which can be syndromic or isolated. Mutations in FGFR1, FGFR2, or FGFR3, among others, are often responsible for these syndromic cases. The associated of FGFR3 mutations with craniosynostosis has been restricted to three mutations, the common p.Pro250Arg in Muenke syndrome, p.Ala391Glu in Crouzon syndrome with acanthosis nigricans, and p.Pro250Leu identified in a family with isolated craniosynostosis. Other FGFR3 mutations result in various skeletal dysplasias: achondroplasia, hypochondroplasia, and thanatophoric dysplasia. Here, we report a novel mutation in exon 8 (IIIc) of FGFR3, p.Ala334Thr, in a young boy with mild craniosynostosis. The mutation segregated with mild craniosynostosis in the family and was absent in 188 normal controls. Alanine 334 is evolutionarily conserved in vertebrates and is located at the amino terminus of the betaF loop in the FGFR3c isoform. The mutation is predicted to alter the protein tertiary structure which may impair its binding to its ligand, FGF1. The identification of a mutation in these clinically heterogeneous disorders can aid recurrence risk assessments. Although the implementation of a stepwise screening strategy is useful in diagnostics, mutations in unscreened regions of genes associated with craniosynostosis may explain a small proportion of craniosynostosis cases. PMID- 22038756 TI - Adipokines: biofactors from white adipose tissue. A complex hub among inflammation, metabolism, and immunity. AB - Until the identification of leptin, the first adipokine discovered in 1994, adipose tissue was considered only as an energy storage tissue. However, it is now clear that adipose tissue is an endocrine/paracrine/autocrine organ, which plays a relevant role in physiopathology of several inflammatory diseases. Actually, it is mainly involved not only in the low-grade inflammatory status in obesity but also in other relevant inflammatory conditions and autoimmune disorders. In this review article, we discuss the main biological activities of leptin, adiponectin, lipocalin-2, resistin, and visfatin, as well as their contributions to certain inflammatory conditions. PMID- 22038758 TI - The interprotein scoring noises in glide docking scores. AB - Small molecule drugs are rarely selective enough to interact solely with their designated targets. Unintended "off-target" interactions often lead to side effects, but also serendipitously lead to new therapeutic uses. Identification of the off-targets of a compound is therefore of significant value to the evaluation of its developmental potential. In computational biology, the strategy of "reverse docking" has been introduced to predict the targets of a compound, which uses a compound to virtually screen a library of proteins, reversing the bait and prey in "normal" docking screenings. The present study shows that, in reverse docking, additional optimization of the scoring function may help to improve the target prediction accuracy. In a case study with the Glide scores, we found that only 57% of the ligand-protein relationships could be correctly identified in a library of 58 complexes whose crystal binding conformations were all able to be accurately reproduced. This was likely a result of the constant over- or under estimation of the scores for specific proteins. In other words, there were interprotein noises in the Glide scores. Introducing a correction term based on protein characteristics improved the target-prediction accuracy by 27% (57-72%). It is our hope that this focused discussion on the Glide scores would invite further efforts to characterize and normalize this type of interprotein noises in all docking scores, so that better target prediction accuracy can be achieved with the strategy of reverse docking. PMID- 22038759 TI - 'Upcycling' organic waste in a world of thinly distributed resources. PMID- 22038760 TI - Clinical relevance of murine double minute 2 single nucleotide polymorphisms 309 in familial myeloproliferative neoplasm. PMID- 22038762 TI - Dinucleating naphthyridine-based ligand for assembly of bridged dicopper(I) centers: three-center two-electron bonding involving an acetonitrile donor. PMID- 22038761 TI - Castration-resistant prostate cancer: many treatments, many options, many challenges ahead. AB - Although the long natural history of prostate cancer presents challenges in the development of novel therapeutics, major contributions have been observed recently. A better understanding of the long-term complications of androgen deprivation has changed the initial approach to most patients with advanced disease. Specifically, recognition of the limitations of prostate-specific antigen has driven the pursuit of new tools capable of becoming true surrogates for disease outcome. Understanding the molecular biology of castration-resistant prostate cancer (CRPC) has led to a dramatic paradigm shift in the treatment of patients with metastatic disease where the androgen receptor becomes a central therapeutic target. Specific adrenal inhibitors and engineered super androgen receptor inhibitors have become the most promising agents in the disease. Novel immune therapies have been shown to improve survival in selected patients with castration-resistant disease despite the inability to impact traditional markers of response. Similarly, agents such as cabazitaxel and abiraterone acetate have demonstrated clinical benefit are now a standard of care in docetaxel-refractory metastatic CRPC patients. All these changes have occurred in a relatively short period and are likely to change the prostate cancer treatment paradigm. This review summarizes the current management of CRPC and discusses potential future directions. PMID- 22038763 TI - Metabolic profiling of beta-cryptoxanthin and its fatty acid esters by supercritical fluid chromatography coupled with triple quadrupole mass spectrometry. AB - In this study, a high-throughput and high-sensitivity profiling system for beta cryptoxanthin (betaCX) and beta-cryptoxanthin fatty acid ester (betaCXFA) was constructed by supercritical fluid chromatography (SFC) coupled with triple quadrupole mass spectrometry (QqQMS). betaCX and nine betaCXFAs were successfully separated within 20 min using a column packed with octadecylsilyl-bonded silica particles. The limit of detection was 540 fmol for the free form and 32-130 fmol for the esterified forms. These results demonstrate that both the throughput and the sensitivity of this SFC-QqQMS system are considerably higher than those of conventional methods. When this system was applied for the analysis of Citrus unshiu, betaCX and five betaCXFAs were directly detected with much simpler sample pre-preparation. The analysis of other citrus fruits indicated that the betaCXFA profiles varied with their breed variety. Furthermore, gas chromatography-mass spectrometry was used to analyze total fatty acid profiles in C. unshiu, and the results revealed that the profiles of fatty acids located in betaCXFA were distinct. This is the first report on the analysis of betaCX and its fatty acid derivatives by SFC-QqQMS. The profiling system developed in this study will be a powerful tool for investigating xanthophyll fatty acid esters. PMID- 22038764 TI - Genomics really gets personal: how exome and whole genome sequencing challenge the ethical framework of human genetics research. AB - Exome sequencing (ES) and whole genome sequencing (WGS) putatively identify all adverse functional alleles of protein-coding genes. Accordingly, while ES/WGS are transformative new tools for gene discovery in human and medical genetics research, they also generate new manifestations of ethical issues related to the consent process, data sharing, and return of results. These manifestations have yet to be comprehensively framed, due in part to the rapidity with which new technologies for ES/WGS are being applied and because of a lack of empirical data to provide guidance. Accordingly, researchers, funding agencies, and policy makers have largely dealt with these issues intuitively. We explain how use of ES/WGS challenges: (i) models under which informed consent is typically obtained; (ii) how harms associated with data sharing are considered; and (iii) the nature of obligations surrounding unanticipated findings. We provide broad guidance about interim ways to contend with these issues and make broad recommendations for areas for novel resource and policy development. PMID- 22038765 TI - Correlation of right frontal hypoperfusion and urinary dysfunction in iNPH: a SPECT study. AB - OBJECTIVES: To elucidate the pathophysiology of urinary dysfunction in idiopathic normal-pressure hydrocephalus (iNPH) by single-photon emission computed tomography (SPECT) and statistical brain mapping. METHODS: Urinary symptoms were observed and N-isopropyl-p-[(123)I]-iodoamphetamine (IMP)-SPECT imaging was performed in 97 patients with clinico-radiologically definite iNPH. The patients included 56 men and 41 women; mean age, 74 years. The statistical difference in normalized mean tracer counts was calculated and visualized between patients with urinary dysfunction of severer degrees (>grade 2/4) and milder degrees (=80 years. Multivariate logistic regression models were constructed to examine treatment; cancer-specific survival was examined using Cox proportional hazards models. RESULTS: A total of 28,902 women were identified, including 2543 women 70 to 79 years old and 1364 >=80 years. For women with early stage (IB1-IIA) tumors, primary surgery was performed in 82.0% of women <50 years old compared with 54.5% of those 70 to 79 years old and 33.2% of those >=80 years old (P < .0001). For women treated surgically, lymphadenectomy was performed in 66.8% of women <50 years old versus 9.1% of patients >=80 years old (P < .0001). Compared with patients <50 years old, those >80 years old were less likely to undergo radical hysterectomy (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.07-0.14) and lymphadenectomy (OR, 0.11; 95% CI, 0.08-0.16) and to receive adjuvant radiation therapy (OR, 0.06; 95% CI, 0.01-0.35). Among women with stage IIB-IVA disease, use of brachytherapy declined with age (P < .0001). For women with stage IB1-IIA tumors, the hazard ratio for death from cancer was 1.35 (95% CI, 1.16-1.58) for women 70 to 79 years old and 2.08 (95% CI, 1.72-2.48) for those >=80 years old compared with younger women. CONCLUSIONS: Elderly women with cervical cancer are less likely to undergo surgery, receive adjuvant radiation, and receive brachytherapy. After adjusting for treatment disparities, cancer-specific mortality is higher in older women. PMID- 22038775 TI - Induced-fit binding of a polyproline helix by a beta-hairpin peptide. PMID- 22038776 TI - The level of cortical afferent inhibition in acute stroke correlates with long term functional recovery in humans. AB - BACKGROUND AND PURPOSE: Using transcranial magnetic stimulation, we investigated short-interval intracortical inhibition and short-latency afferent inhibition in acute ischemic stroke. METHODS: We evaluated short-interval intracortical inhibition and short-latency afferent inhibition in the affected hemisphere and unaffected hemisphere in 16 patients and correlated electrophysiological parameters with outcome at 6 months. RESULTS: Affected hemisphere short-latency afferent inhibition was significantly reduced in patients, and short-latency afferent inhibition level correlated with functional outcome. CONCLUSIONS: Reduced afferent inhibition in acute stroke correlates with long-term recovery. PMID- 22038777 TI - Human pluripotent stem cells for disease modelling and drug screening. AB - Considerable hope surrounds the use of disease-specific pluripotent stem cells to generate models of human disease allowing exploration of pathological mechanisms and search for new treatments. Disease-specific human embryonic stem cells were the first to provide a useful source for studying certain disease states. The recent demonstration that human somatic cells, derived from readily accessible tissue such as skin or blood, can be converted to embryonic-like induced pluripotent stem cells (hiPSCs) has opened new perspectives for modelling and understanding a larger number of human pathologies. In this review, we examine the opportunities and challenges for the use of disease-specific pluripotent stem cells in disease modelling and drug screening. Progress in these areas will substantially accelerate effective application of disease-specific human pluripotent stem cells for drug screening. PMID- 22038778 TI - An efficient combination of supercritical fluid extraction and high-speed counter current chromatography to extract and purify (E)- and (Z)-diastereomers of alpha asarone and beta-asarone from Acorus tatarinowii Schott. AB - In this study, supercritical fluid extraction (SFE) was used to extract essential oil from Acorus tatarinowii Schott under the pressure of 25 MPa and temperature of 35 degrees C. Two (E)- and (Z)-diastereomers of alpha-asarone and beta-asarone were separated and purified by high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (1:0.2:1:0.3, v/v). The separation yielded a total of 39 mg of alpha-asarone and 463 mg of beta-asarone from 1.0 g of essential oil in one-step separation with the purity of 98.9 and 99.1%, respectively, as determined by HPLC. The chemical structures of these compounds were identified by EI-MS, (1)H-, and (13)C-NMR. PMID- 22038779 TI - Evidence of central modulation of bladder compliance during filling phase. AB - AIMS: Bladder compliance is one expression of the pressure and volume relationship as the bladder fills. In addition to passive elements, autonomous micromotional detrusor activity contributes to this relationship. In the mouse cystometric model, compliance pressure contributes to voiding expulsive pressure. During attempts to isolate the detrusor contractile component of this filling pressurization, we found that compliance reversibly diminishes under conditions which remove central control from the micturition cycle. METHODS: Ten mature female mice underwent constant infusion pressure/flow cystometry under urethane anesthesia, and five awake mature female mice underwent constant infusion pressure cystometry. Following baseline cystometry, all mice were anesthetized with isoflurane to abolish the micturition reflex, and cystometry conducted with manual emptying of the bladders. Animals were then allowed to recover from isoflurane to re-establish the micturition reflex, and cystometry again conducted. The urethane group was also studied immediately post-mortem. Repeated measures comparisons of cystometric parameters were made across conditions. RESULTS: Compliance reversibly decreased in all mice with the abolishment of micturition responses by isoflurane anesthesia. A similar decrease was observed immediately post-mortem in the urethaned mice. Bladder filling and voiding were not different between the intact micturition segments of the testing. CONCLUSIONS: Enhanced compliance in mice with intact micturition responses suggests that autonomous micromotional activity is suppressed by central processes during normal filling. Since afferent activity during filling is also determined by the relationship between bladder pressure and volume, a feed forward afferent signal conditioning mechanism may exist, creating novel therapeutic targets for urinary dysfunctions. PMID- 22038780 TI - Developmental plasticity and the origin of novel forms: unveiling cryptic genetic variation via "use and disuse". AB - Natural selection eliminates phenotypic variation from populations, generation after generation-an observation that haunted Darwin. So, how does new phenotypic variation arise, and is it always random with respect to fitness? Repeated behavioral responses to a novel environment-particularly those that are learned are typically advantageous. If those behaviors yield more extreme or novel morphological variants via developmental plasticity, then previously cryptic genetic variation may be exposed to natural selection. Significantly, because the mean phenotypic effect of "use and disuse" is also typically favorable, previously cryptic genetic variation can be transformed into phenotypic variation that is both visible to selection and biased in an adaptive direction. Therefore, use-induced developmental plasticity in a very real sense "creates" new phenotypic variation that is nonrandom with respect to fitness, in contrast to the random phenotypic effects of mutation, recombination, and "direct effects" of environment (stress, nutrition). I offer here (a) a brief review of the immense literature on the effects of "use and disuse" on morphology, (b) a simple yet general model illustrating how cryptic genetic variation may be exposed to selection by developmentally plastic responses that alter trait performance in response to "use and disuse," and (c) a more detailed model of a positive feedback loop between learning (handed behavior) and morphological plasticity (use-induced morphological asymmetry) that may rapidly generate novel phenotypic variation and facilitate the evolution of conspicuous morphological asymmetries. Evidence from several sources suggests that handed behaviors played an important role both in the origin of novel forms (asymmetries) and in their subsequent evolution. PMID- 22038781 TI - On the use of distance constraints in protein-protein docking computations. AB - Protein-protein docking (PPD) is a computational process that predicts the structure of a complex of two interacting proteins from their unbound structures. The accuracy of PPD predictions is low, but can be greatly enhanced if experimentally determined distance data are available for incorporation into the prediction. However, the specific effects of distance constraints on PPD predictions are largely uncharacterized. In this study, we systematically simulated the effects of using distance constraints both on a new distance constraint-driven PPD approach, called DPPD, and also, by re-ranking, on a well established grid-based global search approach. Our results for a PPD benchmark dataset of 84 protein complexes of known structures showed that near 100% docking success rates could be obtained when the number of distance constraints exceeded six, the degrees of freedom of the system, but the success rate was significantly reduced by long distance constraints, large binding-induced conformational changes, and large errors in the distance data. Our results also showed that, under most conditions simulated, even two or three distance constraints were sufficient to achieve a much better success rate than those using a sophisticated physicochemical function to re-rank the results of the global search. Our study provides guidelines for the practical incorporation of experimental distance data to aid PPD predictions. PMID- 22038782 TI - Xanthoangelols isolated from Angelica keiskei inhibit inflammatory-induced plasminogen activator inhibitor 1 (PAI-1) production. AB - The folk medicine Angelica keiskei (Ashitaba) exhibits antitumor, antioxidant and antidiabetic activities and it has recently attracted attention as a health food. Ashitaba is thought to have antithrombotic properties, but this has not yet been scientifically proven. The elevation of plasma plasminogen activator inhibitor 1 (PAI-1), an inhibitor of fibrinolysis results in a predisposition to the risk of thrombosis. The present study showed that Ashitaba exudates injected intraperitoneally and orally administered over long-term suppressed the lipopolysaccharide (LPS) induced PAI-1 increase in mouse plasma. We also found that xanthoangelol, xanthoangelols B and D, the components of Ashitaba exudates, significantly inhibited TNFalpha-induced PAI-1 production from human umbilical vein endothelial cells (HUVECs). These findings suggest that Ashitaba can decrease elevated PAI-1 production, and that daily consumption of Ashitaba product might maintain anticoagulant status by inhibiting elevations in PAI-1 under inflammatory conditions. PMID- 22038783 TI - Brain plasticity for verbal and visual memories in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: an fMRI study. AB - We aimed to identify the brain areas involved in verbal and visual memory processing in normal controls and patients with unilateral mesial temporal lobe epilepsy (MTLE) associated with unilateral hippocampal sclerosis (HS) by means of functional magnetic resonance imaging (fMRI). The sample comprised nine normal controls, eight patients with right MTLE, and nine patients with left MTLE. All subjects underwent fMRI with verbal and visual memory paradigms, consisting of encoding and immediate recall of 17 abstract words and 17 abstract drawings. A complex network including parietal, temporal, and frontal cortices seems to be involved in verbal memory encoding and retrieval in normal controls. Although similar areas of activation were identified in both patient groups, the extension of such activations was larger in the left-HS group. Patients with left HS also tended to exhibit more bilateral or right lateralized encoding related activations. This finding suggests a functional reorganization of verbal memory processing areas in these patients due to the failure of left MTL system. As regards visual memory encoding and retrieval, our findings support the hypothesis of a more diffuse and bilateral representation of this cognitive function in the brain. Compared to normal controls, encoding in the left-HS group recruited more widespread cortical areas, which were even more widespread in the right-HS group probably to compensate for their right mesial temporal dysfunction. In contrast, the right-HS group exhibited fewer activated areas during immediate recall than the other two groups, probably related to their greater difficulty in dealing with visual memory content. PMID- 22038784 TI - Hemoptysis after orthopedic surgery in an adolescent boy. AB - In children, post-obstructive pulmonary edema is a rare condition, caused by a sudden change in upper airway patency. It causes dyspnea, tachypnea, hypoxemia, and at times hemoptysis and respiratory insufficiency. It occurs as a complication in the immediate post-operative period. Pediatricians should be aware of this clinical entity. PMID- 22038785 TI - Parapodial glandular organs in Spiophanes (Polychaeta: Spionidae)-studies on their functional anatomy and ultrastructure. AB - Parapodial glandular organs (PGOs) of Spiophanes (Polychaeta: Spionidae) were studied using light and electron microscopy. These organs are found in parapodia of the mid body region, starting on chaetiger 5 and terminating with the appearance of neuropodial hooks (chaetiger 14 or 15 in adult individuals). Large PGOs in anterior chaetigers display different species-specific types of openings whereas small PGOs in posterior parapodia of the mid body region always open in a simple vertical slit. Each PGO is composed of three main complexes: (1) the glandular sac with several distinct epithelia of secretory cells and secretory cell complexes and the reservoir filled with fibrous material, (2) the gland associated chaetal complex (including the region of chaetoblasts and follicle cells, follicular canals, two chaetal collector canals, the combined conducting canal, the chaetal spreader including the opening of the glandular organ with associated type-1 secretory cells, and the gland-associated chaetae), and (3) a bilayered musculature surrounding the gland. A considerable number of different cell types are involved in the secretory activity, in the guidance of the gland associated chaetae, and in the final expulsion of the fibrous secretion at the opening slit. Among these different cell types the type-5 secretory cells of the proximal glandular complex with their cup-shaped microvilli emanating thick microfibrils into the lumen of the glandular sac are most conspicuous. Secretory cells with cup-shaped microvilli being involved in the production of beta-chitin microfibrils have so far only been reported from some representatives of the deep sea inhabiting Siboglinidae (Polychaeta). We suggest that the gland-associated chaetae emerging from inside the PGOs of Spiophanes are typical annelid chaetae formed by chaetoblasts and follicle cells. Functional morphology implies the crucial role of PGOs in tube construction. Furthermore, the PGOs are discussed in consideration of phylogenetic aspects. PMID- 22038786 TI - Ruthenium nanoparticles stabilized by N-heterocyclic carbenes: ligand location and influence on reactivity. PMID- 22038787 TI - Graft copolymer composed of cationic backbone and bottle brush-like side chains as a physically adsorbed coating for protein separation by capillary electrophoresis. AB - To stabilize electroosmotic flow (EOF) and suppress protein adsorption onto the silica capillary inner wall, a cationic hydroxyethylcellulose-graft-poly (poly(ethylene glycol) methyl ether methacrylate) (cat-HEC-g-PPEGMA) graft copolymer composed of cationic backbone and bottle brush-like side chains was synthesized for the first time and used as a novel physically adsorbed coating for protein separation by capillary electrophoresis. Reversed (anodal) and very stable EOF was obtained in cat-HEC-g-PPEGMA-coated capillary at pH 2.2-7.8. The effects of degree of cationization, PEGMA grafting ratio, PEGMA molecular mass, and buffer pH on the separation of basic proteins were investigated. A systematic comparative study of protein separation in bare and HEC-coated capillaries and in cat-HEC-g-PPEGMA-coated capillary was also performed. The basic proteins can be well separated in cat-HEC-g-PPEGMA-coated capillary over the pH range of 2.8-6.8 with good repeatability and high separation efficiency, because the coating combines good protein-resistant property of bottle brush-like PPEGMA side chains with excellent coating ability of cat-HEC backbone. Besides its success in separation of basic proteins, the cat-HEC-g-PPEGMA coating was also superior in the fast separation of other protein samples, such as protein mixture, egg white, and saliva, which indicates that it is a promising coating for further proteomics analysis. PMID- 22038788 TI - Opening the door for hepatitis C virus infection in genetically humanized mice. PMID- 22038789 TI - The long and the short of interferon-gamma-inducible protein 10 in hepatitis C virus infection. PMID- 22038790 TI - Exhausted or just sleeping: awakening virus-specific responses in chronic hepatitis C virus infection. PMID- 22038791 TI - Boceprevir (Victrelis) for HCV: V is for victory and very complex. PMID- 22038792 TI - Tamsulosin reduces nighttime urine production in benign prostatic hyperplasia patients with nocturnal polyuria: a prospective open-label long-term study using frequency-volume chart. AB - AIMS: The effects of tamsulosin treatment on changes in frequency-volume chart (FVC) data, especially nighttime urine production, over time were assessed, and the mechanisms underlying the improvement of nocturia in benign prostatic hyperplasia (BPH) patients with nocturnal polyuria (NP) are discussed. METHODS: A total of 104 patients with lower urinary tract symptoms secondary to BPH were enrolled. After enrollment in the study, the patients were treated with tamsulosin (0.2 mg) once daily. Visits were scheduled every 4 weeks until week 12 (month 3) after study entry, and then every 12 weeks subsequently. All patients completed the International Prostate Symptom Score (IPSS), quality of life (QOL) index, and 3-day FVC, and underwent uroflowmetry at enrollment and on each visit. RESULTS: Eighty-two patients (mean age: 70.9 +/- 7.1 years) were analyzed for 24 months after treatment. Patients were divided into two groups, NP and nonNP, based on FVC outcome. The IPSS, QOL index, and maximum flow rate improved during the 24-month period after treatment in both groups. Mean daytime urine volume significantly increased in the NP group, but no changes were detected in the nonNP group. Mean nighttime urine frequency significantly decreased in the NP group over a 24-month period, and was associated with a significant decrease in nighttime urine volume that was not found in the nonNP group. Maximum voided volume increased most months after treatment in both groups. CONCLUSIONS: The present long-term prospective study using FVC demonstrated that tamsulosin reduced nighttime urine production in BPH patients with NP. PMID- 22038793 TI - Barriers and potential solutions toward optimal prophylaxis against deep vein thrombosis for hospitalized medical patients: a survey of healthcare professionals. AB - OBJECTIVE: Deep vein thrombosis (DVT) prophylaxis remains underused in hospitalized medical patients despite strong recommendations that at-risk patients should receive prophylaxis. To understand this gap between knowledge and practice, we surveyed clinicians' perceptions about the importance of DVT prophylaxis, barriers to guideline implementation, and interventions to optimize prophylaxis. METHODS: Paper- and electronic mail-based surveys were sent to 1553 internists, nurses, pharmacists, and physiotherapists in Ontario, Canada. Responses were scored on 7-point Likert scales. An important barrier to optimal DVT prophylaxis was 1 with a mean score >=5, and interventions with high potential success or feasibility were those with mean scores >=5. RESULTS: DVT prophylaxis was perceived as important by all clinician groups but this did not appear to translate into knowledge about underutilization of current DVT prophylaxis strategies. Physicians and pharmacists recognized the underuse of DVT prophylaxis in medical patients, while nurses and physiotherapists tended to perceive prophylaxis strategies as appropriate. Lack of clear indications and contraindications for prophylaxis and concerns about bleeding risks were perceived as important barriers. Preprinted orders were considered the most potentially successful and feasible way to optimize prophylaxis. CONCLUSIONS: A considerable barrier to optimal DVT prophylaxis utilization may be that those healthcare providers best able to conduct a daily assessment of patients' need for prophylaxis underrecognize the problem that prophylaxis is underutilized in this population. Interventions to bridge the gap between knowledge and practice should consider preprinted orders outlining DVT risk factors, and educating front line care providers prior to implementation of a top-down approach. PMID- 22038794 TI - hCINAP is an atypical mammalian nuclear adenylate kinase with an ATPase motif: structural and functional studies. AB - Human coilin interacting nuclear ATPase protein (hCINAP) directly interacts with coilin, a marker protein of Cajal Bodies (CBs), nuclear organelles involved in the maturation of small nuclear ribonucleoproteins UsnRNPs and snoRNPs. hCINAP has previously been designated as an adenylate kinase (AK6), but is very atypical as it exhibits unusually broad substrate specificity, structural features characteristic of ATPase/GTPase proteins (Walker motifs A and B) and also intrinsic ATPase activity. Despite its intriguing structure, unique properties and cellular localization, the enzymatic mechanism and biological function of hCINAP have remained poorly characterized. Here, we offer the first high resolution structure of hCINAP in complex with the substrate ADP (and dADP), the structure of hCINAP with a sulfate ion bound at the AMP binding site, and the structure of the ternary complex hCINAP-Mg(2+) ADP-Pi. Induced fit docking calculations are used to predict the structure of the hCINAP-Mg(2+) ATP-AMP ternary complex. Structural analysis suggested a functional role for His79 in the Walker B motif. Kinetic analysis of mutant hCINAP-H79G indicates that His79 affects both AK and ATPase catalytic efficiency and induces homodimer formation. Finally, we show that in vivo expression of hCINAP-H79G in human cells is toxic and drastically deregulates the number and appearance of CBs in the cell nucleus. Our findings suggest that hCINAP may not simply regulate nucleotide homeostasis, but may have broader functionality, including control of CB assembly and disassembly in the nucleus of human cells. PMID- 22038795 TI - Continuous versus intermittent inhaled corticosteroid (budesonide) for mild persistent asthma in children--not too much, not too little. PMID- 22038796 TI - A brief review of coarse-grained and other computational studies of molecularly imprinted polymers. AB - Molecular imprinting is an established method for the creation of artificial recognition sites in synthetic materials through polymerization and cross-linking in the presence of template molecules. Removal of the templates leaves cavities that are complementary to the template molecules in size, shape, and functionality. In recent years, various theoretical and computational models have been developed as tools to aid in the design of molecularly imprinted polymers (MIPs) or to provide insight into the features that determine MIP performance. These studies can be grouped into two general approaches-screening for possible functional monomers for particular templates and macromolecular models focusing on the structural characterization of the imprinted material. In this review, we pay special attention to coarse-grained models that characterize the functional heterogeneity in imprinted pores, but also cover recent advances in atomistic and first principle studies. We offer a critical assessment of the potential impact of the various models towards improving the state-of-the-art of molecular imprinting. PMID- 22038797 TI - Survey of the 2009 commercial optical biosensor literature. AB - We took a different approach to reviewing the commercial biosensor literature this year by inviting 22 biosensor users to serve as a review committee. They set the criteria for what to expect in a publication and ultimately decided to use a pass/fail system for selecting which papers to include in this year's reference list. Of the 1514 publications in 2009 that reported using commercially available optical biosensor technology, only 20% passed their cutoff. The most common criticism the reviewers had with the literature was that "the biosensor experiments could have been done better." They selected 10 papers to highlight good experimental technique, data presentation, and unique applications of the technology. This communal review process was educational for everyone involved and one we will not soon forget. PMID- 22038798 TI - Molecular imprinting in monolayer surfaces. AB - A comprehensive report on molecularly imprinted monolayers (MIMs) is presented, but does not include bulk-polymer thin film coatings on surfaces, inorganic surface imprinting, polymer grafting and layer-by-layer methods. Due to difficulties in imprinting large molecules and obtaining fast binding responses with traditional network polymer materials, MIMs have been developed with the aim of enhancing mass-transfer of analytes in imprinted materials. Three approaches to MIM fabrication have been developed with respect to the formation of the pre organized template-matrix complex. In the first approach, the molecular binding sites are formed in a monolayer on a glass or gold surface. The second approach uses a template-macromolecule complex to form binding sites in the solution phase that are immobilized onto a surface; and the third approach transfers an imprinted Langmuir film onto a gold surface. Mass transfer in these MIMs in most cases is on the order of minutes, and both small and large molecules (proteins) have been imprinted. PMID- 22038799 TI - Oxidoreductase activity of multifunctional monoclonal antibody B13-DE1. AB - The monoclonal antibody B13-DE1 binds fluorescein, several fluorescein derivatives, and three peptide mimotopes. Our results revealed that this antibody also catalyzed the redox reaction of resazurin to resorufin, which are both structurally related to fluorescein. By using sodium sulfite as a reducing agent, the antibody B13-DE1 lowered the activation energy of this reaction. The Michaelis-Menten constant and turnover number of the catalyzed reaction were determined as 4.2 umol/l and 0.0056 s(-1) , respectively. Because the results showed that fluorescein inhibited the catalytic activity of the antibody, we assume that the antigen-binding site and the catalytic active site are identical. PMID- 22038800 TI - Identification and evaluation of inhibitors of the EhGEF1 protein from Entamoeba histolytica. AB - The Dbl family of guanine nucleotide exchange factors (GEFs) is made up of a vast array of members that participate in the activation of the Rho family of small GTPases. Dbl-family proteins promote the exchange of guanosine diphosphate/guanosine triphosphate (GDP/GTP) in their target molecules, resulting in the activation of a variety of signaling pathways involved in diverse cellular events, such as actin-cytoskeleton remodeling, cellular invasion, cell movement, and other functions. It has been reported that members of the Dbl family have important roles in several cellular events in Entamoeba histolytica. These include activation of the actin cytoskeleton, cytokinesis, capping, uroid formation, cellular proliferation, erythrophagocytosis, cell migration, and chemotaxis. Here, we report the identification and testing of inhibitors of the E. histolytica guanine nucleotide exchange factor 1 (EhGEF1) protein (the research compounds 2BYRF, 2BY05, 2BYT6, 2BYLX, and 2BYPD), which decreased the in vitro ability of the protein to exchange GDP/GTP at its target GTPases, EhRacG and EhRho1, by 14.9-85.2%. Interestingly, the drug 1,1'-(1,2-phenylene)-bis-(1H pyrrole-2,5-dione), which completely inhibits the GEF activity of the Trio protein in human cells, decreases the GEF activity of the EhGEF1 protein on the EhRacG and EhRho1 GTPases by 55.7% and 3.2%, respectively. The identification and evaluation of such inhibitors opens up the possibility of obtaining a new pharmacological tool to study the function of amoeba GEF proteins, their roles in various Rho GTPase-mediated signaling pathways, and the repercussions of modulating their activities with respect to several mechanisms related to E. histolytica pathogenesis. PMID- 22038801 TI - Exploring variation in binding of Protein A and Protein G to immunoglobulin type G by isothermal titration calorimetry. AB - Bacterial Protein A (PrtA) and Protein G (PrtG) are widely used for affinity purification of antibodies. An understanding of how PrtA and PrtG bind to different isotypes of immunoglobulin type G (IgG) and to their corresponding Fc fragments is essential for the development of PrtA and PrtG mimetic ligands and for the establishment of generic processes for the purification of various antibodies. In this paper, the interactions between the two IgG-binding proteins and IgG of two different subclasses, IgG1 and IgG4, as well as their analogous Fc fragments have been studied by isothermal titration calorimetry. The results indicate that both protein ligands bind IgG and Fc fragments strongly with Ka values in the range of 10(7) -10(8) M(-1) and for both ligands, the interaction with both IgG isotypes is enthalpically driven though entropically unfavorable. Moreover, variation in the standard entropic and standard enthalpic contribution to binding between the two isotypes as well as between IgG and Fc fragment implies that the specific interaction with PrtA varies according to IgG isotype. In contrast to PrtA, PrtG bound to F(ab')(2) fragment with a Ka value of 5.1 * 10(5) M(-1) ; thus underscoring the usefulness of PrtA as a preferred ligand for generic antibody purification processes. PMID- 22038802 TI - Label-free detection of enhanced saccharide binding at pH 7.4 to nanoparticulate benzoboroxole based receptor units. AB - Nanoparticles modified with either 6-amino-1-hydroxy-2,1-benzoxaborolane (3 aminobenzoboroxole) or 3-aminophenylboronic acid were prepared by nucleophilic substitution of a styrene-co-DVB-co-vinylbenzylchloride latex (25 nm). Isothermal titration calorimetry (ITC) was used as a label-free detection method for the analysis of the binding between monosaccharides and these two differently derivatized nanoparticle systems at pH 7.4. Because ITC reveals, thermodynamical parameters such as the changes in enthalpy DeltaH, free energy DeltaG, and entropy DeltaS, possible explanations for the higher binding constants can be derived in terms of entropy and enthalpy changes. In case of the modified nanoparticles, the free energy of binding is dominated by the entropy term. This shows that interfacial effects, besides the intrinsic affinity, lead to a higher binding constant compared with the free ligand. The highest binding constant was found for fructose binding to the benzoboroxole modified nanoparticles: Its value of 1150 M(-1) is twice as high as for the free benzoboroxole and five times as high as with phenylboronic acid or 3-aminophenylboronic acid. In contrast to the binding of fructose to free boronic acids, which is an enthalpically driven process, the binding of fructose to the modified nanoparticles is dominated by the positive entropy term. PMID- 22038803 TI - Affinity and catalytic heterogeneity and metal-dependence of polyclonal myelin basic protein-hydrolyzing IgGs from sera of patients with systemic lupus erythematosus. AB - It was shown using enzyme-linked immunosorbent assay (ELISA) that titers of antibodies against human myelin basic protein (hMBP) in systemic lupus erythematosus (SLE) patients 4.2-fold higher than in healthy individuals, but 2.1 fold lower than in patients with multiple sclerosis (MS). Approximately 86% electrophoretically and immunologically homogeneous SLE immunoglobulin Gs (IgGs) purified using several affinity resins including Sepharose with immobilized hMBP specifically hydrolyze only hMBP but not many other tested proteins. Several rigid criteria were applied to show that the hMBP-hydrolyzing activity is an intrinsic property of SLE IgGs but not from healthy donors. In contrast to MS IgGs, abzymes from SLE patients are more sensitive to ethylenediaminetetraacetic acid and less sensitive to specific inhibitors of serine-like proteases. We present the first evidence demonstrating a significant diversity of different fractions of SLE IgGs in their affinity for hMBP-Sepharose, the ability of IgGs to hydrolyze hMBP at different optimal pHs (5-10) and be activated by different metal ions: Ca(2+) > Mg(2+) >= Co(2+) >= Fe(2+) >= Ni(2+) >= Zn(2+) >= Cu(2+) >= Mn(2+) . Combinations of Ca(2+) + Mg(2+) and Ca(2+) + Co(2) lead to a significant increase in the antibody proteolytic activity as compared with Ca(2+) , Co(2+) , or Mg(2+) ions taken separately. Our findings suggest that the immune systems of individual SLE similar to MS patients can generate a variety of anti-hMBP abzymes with different catalytic properties, which can attack hMBP of myelin-proteolipid shell of axons and play an important role in pathogenesis not only MS but also SLE patients. PMID- 22038804 TI - Study of specific interaction between nucleotides and dye support by nuclear magnetic resonance. AB - The binding between four matrices (beaded cellulose, cellulose acetate, cellulose triacetate and Sepharose CL-6B) and beaded cellulose derivatized with a thiacarbocyanine dye with 5'-mononucleotides is investigated by Saturation Transfer Difference Nuclear Magnetic Resonance (STD-NMR) technique. This procedure intends to identify unspecific interactions between 5'-mononucleotides and matrices commonly used in affinity chromatography systems and also clarify the contribution of a thiacarbocyanine dye immobilized onto cellulose beads in a biorecognition process. The differences between non-derivatized and derivatized beaded cellulose evidence the contribution of thiacarbocyanine dye in the observed interaction. STD-NMR experiments show that Sepharose CL- 6B interact less with the 5'-mononucleotides comparatively with beaded cellulose. Indeed, beaded cellulose shows nonspecific interactions with almost all 5' mononucleotides that compromises the specificity of the interaction between the thiacarbocyanine dye immobilized with the 5'-mononucleotides. The cellulose matrices where the hydroxyl groups are replaced by acetate and triacetate groups do not exhibit binding response to the 5'- mononucleotides, whereas the thiacarbocyanine dye contribution is evidenced by the reinforcement of the interactions with the sugar moiety of 5'-GMP and 5'-UMP and with base of 5'-AMP, 5'-CMP and 5'-TMP. This screening of the nucleotide atoms involved in the binding to the supports can be very useful in chromatography evaluations in which dye affinity chromatography supports may be used, such as purification of nucleic acids. PMID- 22038805 TI - Structural analysis of zinc-finger (TTK) + [Cu(BPA)]2+ /[Cu(IDB)]2+ + DNA complexes: an investigation by molecular dynamics simulation. AB - In the present study, the molecular dynamics simulation technique is employed to investigate the hydrogen abstraction possibility from sugar of DNA in two designed complexes of copper-based chemical nuclease [Cu(BPA)](2+) bis(2 pyridylmethyl) amine (BPA) or [Cu(IDB)](2+) N,N-bis(2-benzimidazolylmethyl) amine (IDB) bound to the zinc finger protein Tramtrack (TTK). The simulated results show that each of the designed complexes can form a stable conformation within 30 ns of simulation time with the substrate OOH(-) and an 18-base pair (bp) DNA segment and is located in the major groove of the DNA segment. The active terminal O atom of the OOH(-) substrate is found in close proximity to the target C2'H, C3'H, C4'H or C5'H proton of the DNA in TTK + [Cu(BPA)OOH](+) + DNA or TTK + [Cu(IDB)OOH](+) + DNA complex, which is crucial to propose the hydrogen abstraction possibility that is responsible for the DNA cleavage. The positions of copper-based chemical nucleases bound to TTK may substantially influence the hydrogen abstraction possibility. The structures and sizes of ligands in copper based nucleases are also found to have influence on the order of difficulty of the hydrogen abstraction from the sugars of DNA. PMID- 22038806 TI - Aromatic side-chain cluster of biotin binding site of avidin allows circular dichroism spectroscopic investigation of its ligand binding properties. AB - Promiscuous ligand binding by hen egg-white avidin has been demonstrated and studied by using circular dichroism (CD) spectroscopy complemented by molecular docking calculations. It has been shown that the biotin-binding pocket of avidin is able to accommodate a wide variety of chemical compounds including therapeutic drugs (e.g., thalidomide, NSAIDs, antihistamines), natural compounds (bilirubin, myristic acid), and synthetic agents (xanthenone dyes). The cluster of aromatic residues located at the biotin-binding pocket renders the intrinsic CD spectrum of avidin sensitive to ligand binding that results in the increase of the vibronic components of the (1) L(b) transition of the Trp residues. Extrinsic (induced) CD bands measured with chemically diverse avidin ligands are generated by intramolecular coupled oscillator (e.g., bilirubin) or by intermolecular ligand-Trp exciton coupling mechanism [e.g., 2-(4'-hydroxyazobenzene)-benzoic acid (HABA)]. Among the compounds of which avidin-binding affinity constants have been calculated, two novel high-affinity ligands, flufenamic acid and an enzyme inhibitor thiazole derivative have been identified (K(d) ~ 1 MUM). Avidin binding mode of the ligand molecules has been discussed in the light of docking results. The induced CD profile of the thiazole derivative has been correlated with the stereochemistry of its docked conformation. The important role in the ligand binding of a polar side-chain cluster at the bottom of the biotin-binding cavity as well as the analogous avidin-binding mode of HABA and fenamic acid type NSAIDs have been proposed. PMID- 22038807 TI - Structural and thermodynamic consequences of the replacement of zinc with environmental metals on estrogen receptor alpha-DNA interactions. AB - Estrogen receptor alpha (ERalpha) acts as a transcription factor by virtue of the ability of its DNA-binding (DB) domain, comprised of a tandem pair of zinc fingers, to recognize the estrogen response element within the promoters of target genes. Herein, using an array of biophysical methods, we probe the structural consequences of the replacement of zinc within the DB domain of ERalpha with various environmental metals and their effects on the thermodynamics of binding to DNA. Our data reveal that whereas the DB domain reconstituted with divalent ions of zinc, cadmium, mercury, and cobalt binds to DNA with affinities in the nanomolar range, divalent ions of barium, copper, iron, lead, manganese, nickel, and tin are unable to regenerate DB domain with DNA-binding potential, although they can compete with zinc for coordinating the cysteine ligands within the zinc fingers. We also show that the metal-free DB domain is a homodimer in solution and that the binding of various metals only results in subtle secondary and tertiary structural changes, implying that metal coordination may only be essential for binding to DNA. Collectively, our findings provide mechanistic insights into how environmental metals may modulate the physiological function of a key nuclear receptor involved in mediating a plethora of cellular functions central to human health and disease. PMID- 22038808 TI - Polyamide recognition-mass spectrometry for distinguishing hairpin DNA from coil DNA. AB - The discrimination between hairpin DNA and coil DNA has been well achieved through polyamides as probes by electrospray ionization (ESI) mass spectrometry. ESI mass spectra showed that polyamides bind to hairpin DNA with high selectivity, and almost no binding with coil DNA. In addition, the noncovalent interaction between polyamides and hairpin DNA was also studied; the results show that hairpin DNA with longer stem and polyamides with more heterocycles have higher binding affinity and stability in gas phase. PMID- 22038809 TI - Interaction of reduced nicotinamide adenine dinucleotide with an antifreeze protein from Dendroides canadensis: mechanistic implication of antifreeze activity enhancement. AB - Antifreeze proteins (AFPs) found in many organisms can noncolligatively lower the freezing point of water without altering the melting point. The difference between the depressed freezing point and the melting point, termed thermal hysteresis (TH), is usually a measure of the antifreeze activity of AFPs. Certain low molecular mass molecules and proteins can further enhance the antifreeze activity of AFPs. Interaction between an enhancer and arginine is known to play an important role in enhancing the antifreeze activity of an AFP from the beetle Dendroides canadensis (DAFP-1). Here, we examined the enhancement effects of several prevalent phosphate-containing coenzymes on the antifreeze activity of DAFP-1. beta-Nicotinamide adenine dinucleotide (reduced) (NADH) is identified as the most efficient enhancer of DAFP-1, which increases the antifreeze activity of DAFP-1 by around 10 times. Examination of the enhancement abilities of a series of NADH analogs and various molecular fragments of NADH reveals that the modifications of nicotinamide generate a series of highly efficient enhancers, though none as effective as NADH itself, and the whole molecular structure of NADH is necessary for its highly efficient enhancement effect. We also demonstrated a 1:1 binding between DAFP-1 and NADH. The binding was characterized by high-performance liquid chromatography (HPLC) using the gel filtration method of Hummel and Dreyer. The data analysis suggests binding between DAFP-1 and NADH with a dissociation constant in the micromolar range. Interactions between DAFP-1 and NADH are discussed along with molecular mechanisms of enhancer action. PMID- 22038810 TI - Determinants of sweetness in proteins: a topological approach. AB - Sweet taste in mammals is accounted for by a single receptor that shares homology with a metabotropic glutamate receptor. Most sweeteners are small molecular weight molecules that interact with small cavities in the so-called Venus Flytrap domains of the sweet receptor. The mechanism of action of larger molecules such as sweet proteins is, however, more difficult to interpret. The first and still the only general mechanism proposed for the action of sweet proteins, the "wedge model," hypothesizes that proteins bind to an external binding site of the active conformation of the sweet receptor. Here, I have extended the concept that inspired the wedge model using a combination of structural analysis, bioinformatics tools, and a relatively large dataset of mutations of the two most extensively studied sweet proteins, monellin and brazzein. I show here that it is possible to single out, among the ensemble yielded by low-resolution docking, a unique complex that satisfies simple topological constraints. These models of the complexes of monellin and brazzein are fully consistent with experimental evidence, thus providing predicting power for further validation of the wedge model. PMID- 22038811 TI - Modelling the interaction between the p53 DNA-binding domain and the p28 peptide fragment of Azurin. AB - Recent experimental data reveal that the peptide fragment of Azurin called p28, constituted by the amino acid residues from 50 to 77 of the whole protein, retains both the Azurin cellular penetration ability and antiproliferative activity. p28 is hypothesized to act by stabilizing the well-known tumour suppressor p53 via a pathway independent from the oncogene Mdm2, which is the main p53 down-regulator, with its anticancer potentiality being probably connected with the binding of its amino acid residues 11 to 18 to p53. However, the p28 mode of action has not been completely elucidated yet, mostly because the details of the p28 interaction with p53 are still unknown. In the present study, computational docking modelling supported by cluster analysis, molecular dynamics simulations and binding free energy calculations have been performed to model the interaction between the DNA-binding domain (DBD) of p53 and the p28 fragment. Since the folding state of p28 when interacting with p53 inside the cell is not known, both the folded and the unfolded structures of this peptide have been taken into consideration. In both the cases, we have found that p28 is able to form with DBD a complex characterized by favourable negative binding free energy, high shape complementarity, and the presence of several hydrogen bonds at the interface. These results suggest that p28 might exert its anticancer action by hampering the binding of ubiquitin ligases to DBD, susceptible to promoting the p53 proteasomal degradation. PMID- 22038812 TI - Open-ITC: an alternate computational approach to analyze the isothermal titration calorimetry data of complex binding mechanisms. AB - Isothermal titration calorimetry (ITC) is an important technique used in quantitatively analyzing the global mechanism of protein-protein or protein ligand interactions through thermodynamic measurements. Among different binding mechanisms, the parallel and ligand induced protein oligomerization mechanisms are technically difficult to analyze compared with a sequential binding mechanism. Here, we present a methodology implemented as a program "Open-ITC" that eliminates the need for exact analytical expressions for free ligand concentrations [L] and mole fractions of bound ligand theta that are required for the thermogram analysis. Adopting a genetic algorithm-based optimization, the thermodynamic parameters are determined, and its standard error is evaluated at the global minimum by calculating the Jacobian matrix. This approach yielded a statistically consistent result for a single-site and a two-site binding protein ligand system. Further, a comparative simulation of a two-step sequential, a parallel, and a ligand induced oligomerization model revealed that their mechanistic differences are discernable in ITC thermograms, only if the first binding step is weaker compared with the second binding step (K(1) 7 nights/month. HPV16/18 accounted for 30 and 82.2% of HPV-positive women in the general population and ICC, respectively. Cervical cancer prevention policies should take into account the relatively low HPV prevalence in this population. PMID- 22038831 TI - Comparative repeatability of two handheld fractional exhaled nitric oxide monitors. AB - BACKGROUND: The use of portable fractional exhaled nitric oxide (FENO) devices is increasingly common in the diagnosis and management of allergic airways inflammation. METHODS: We tested two handheld FENO devices, to determine (a) if there was adequate intradevice repeatability to allow the use of single breath testing, and (b) if the devices could be used interchangeably. In a mixed pediatric population, including normal, asthmatic, and children with peanut allergies, 858 paired values were collected from the NIOX-MINO(r) and/or the NObreath(r) devices. RESULTS: The NIOX-MINO(r) showed excellent repeatability (mean difference of 0.1 with 95% limits of agreement between -7.93 to 7.72 ppb), while the NObreath(r) showed good repeatability (mean difference of -1.61 with 95% limits of agreement between -14.1 and 10.8 ppb). Intradevice repeatability was good but not adequate and the NIOX-MINO(r) systematically produced higher results than the NObreath(r) [mean difference of 7.8 ppb with 95% limits of agreement from -11.55 to 27.52 ppb (-33% to 290%)]. CONCLUSIONS: Our results support the manufacturer's advice that single breath testing is appropriate for the NIOX-MINO(r). NObreath(r) results indicate that the mean of more than one breath should be utilized. The devices cannot be used interchangeably. PMID- 22038832 TI - Potential scenarios for nanomaterial release and subsequent alteration in the environment. AB - The risks associated with exposure to engineered nanomaterials (ENM) will be determined in part by the processes that control their environmental fate and transformation. These processes act not only on ENM that might be released directly into the environment, but more importantly also on ENM in consumer products and those that have been released from the product. The environmental fate and transformation are likely to differ significantly for each of these cases. The ENM released from actual direct use or from nanomaterial-containing products are much more relevant for ecotoxicological studies and risk assessment than pristine ENM. Released ENM may have a greater or lesser environmental impact than the starting materials, depending on the transformation reactions and the material. Almost nothing is known about the environmental behavior and the effects of released and transformed ENM, although these are the materials that are actually present in the environment. Further research is needed to determine whether the release and transformation processes result in a similar or more diverse set of ENM and ultimately how this affects environmental behavior. This article addresses these questions, using four hypothetical case studies that cover a wide range of ENM, their direct use or product applications, and their likely fate in the environment. Furthermore, a more definitive classification scheme for ENM should be adopted that reflects their surface condition, which is a result of both industrial and environmental processes acting on the ENM. The authors conclude that it is not possible to assess the risks associated with the use of ENM by investigating only the pristine form of the ENM, without considering alterations and transformation processes. PMID- 22038833 TI - Disruption of cytokeratin-8 interaction with F508del-CFTR corrects its functional defect. AB - We have previously reported an increased expression of cytokeratins 8/18 (K8/K18) in cells expressing the F508del mutation of cystic fibrosis transmembrane conductance regulator (CFTR). This is associated with increased colocalization of CFTR and K18 in the vicinity of the endoplasmic reticulum, although this is reversed by treating cells with curcumin, resulting in the rescue of F508del CFTR. In the present work, we hypothesized that (i) the K8/K18 network may interact physically with CFTR, and that (ii) this interaction may modify CFTR function. CFTR was immunoprecipitated from HeLa cells transfected with either wild-type (WT) CFTR or F508del-CFTR. Precipitates were subjected to 2D-gel electrophoresis and differential spots identified by mass spectrometry. K8 and K18 were found significantly increased in F508del-CFTR precipitates. Using surface plasmon resonance, we demonstrate that K8, but not K18, binds directly and preferentially to the F508del over the WT human NBD1 (nucleotide-binding domain-1). In vivo K8 interaction with F508del-CFTR was confirmed by proximity ligation assay in HeLa cells and in primary cultures of human respiratory epithelial cells. Ablation of K8 expression by siRNA in F508del-expressing HeLa cells led to the recovery of CFTR-dependent iodide efflux. Moreover, F508del expressing mice topically treated with K8-siRNA showed restored nasal potential difference, equivalent to that of WT mice. These results show that disruption of F508del-CFTR and K8 interaction leads to the correction of the F508del-CFTR processing defect, suggesting a novel potential therapeutic target in CF. PMID- 22038834 TI - A novel mutation within the MIR96 gene causes non-syndromic inherited hearing loss in an Italian family by altering pre-miRNA processing. AB - The miR-96, miR-182 and miR-183 microRNA (miRNA) family is essential for differentiation and function of the vertebrate inner ear. Recently, point mutations within the seed region of miR-96 were reported in two Spanish families with autosomal dominant non-syndromic sensorineural hearing loss (NSHL) and in a mouse model of NSHL. We screened 882 NSHL patients and 836 normal-hearing Italian controls and identified one putative novel mutation within the miR-96 gene in a family with autosomal dominant NSHL. Although located outside the mature miR-96 sequence, the detected variant replaces a highly conserved nucleotide within the companion miR-96*, and is predicted to reduce the stability of the pre-miRNA hairpin. To evaluate the effect of the detected mutation on miR-96/mir-96* biogenesis, we investigated the maturation of miR-96 by transient expression in mammalian cells, followed by real-time reverse-transcription polymerase chain reaction (PCR). We found that both miR-96 and miR-96* levels were significantly reduced in the mutant, whereas the precursor levels were unaffected. Moreover, miR-96 and miR-96* expression levels could be restored by a compensatory mutation that reconstitutes the secondary structure of the pre-miR-96 hairpin, demonstrating that the mutation hinders precursor processing, probably interfering with Dicer cleavage. Finally, even though the mature miR-96 sequence is not altered, we demonstrated that the identified mutation significantly impacts on miR-96 regulation of selected targets. In conclusion, we provide further evidence of the involvement of miR-96 mutations in human deafness and demonstrate that a quantitative defect of this miRNA may contribute to NSHL. PMID- 22038835 TI - Loss of ceramide synthase 3 causes lethal skin barrier disruption. AB - The stratum corneum as the outermost epidermal layer protects against exsiccation and infection. Both the underlying cornified envelope (CE) and the intercellular lipid matrix contribute essentially to these two main protective barriers. Epidermis-unique ceramides with ultra-long-chain acyl moities (ULC-Cers) are key components of extracellular lipid lamellae (ELL) and are bound to CE proteins, thereby contributing to the cornified lipid envelope (CLE). Here, we identified human and mouse ceramide synthase 3 (CerS3), among CerS1-6, to be exclusively required for the ULC-Cer synthesis in vitro and of mouse CerS3 in vivo. Deficiency of CerS3 in mice results in complete loss of ULC-Cers (>=C26), lack of continuous ELL and a non-functional CLE. Consequently, newborn mutant mice die shortly after birth from transepidermal water loss. Mutant skin is prone to Candida albicans infection highlighting ULC-Cers to be pivotal for both barrier functions. Persistent periderm, hyperkeratosis and deficient cornification are hallmarks of mutant skin demonstrating loss of Cers to trigger a keratinocyte maturation arrest at an embryonic pre-barrier stage. PMID- 22038836 TI - The comparison of two column classification systems during the chromatographic analysis of steroids. AB - Nowadays, due to the availability of hundreds of brands of reversed-phase liquid chromatographic columns, the selection of suitable columns can be difficult. Therefore, a good characterization and classification system is very important. Among published papers, the classification system based on quantitative structure retention relationships and a method developed at the Katholieke Universiteit Leuven also exist. In quantitative structure-retention relationships, retention is evaluated in terms of the chemical structure of the analytes and the physicochemical properties of both the stationary and mobile phase. The second system allows to rank columns due to the values of four parameters and the calculation of specific F(KUL)-values for a reference column and to be compared with others. In this paper, the classification systems based both on quantitative structure-retention relationships and the F(KUL)-values using principal components analysis were compared. Moreover, the proposed column ranking systems have been checked in clinical practice case considering liquid chromatography determination of six steroid hormones in urine samples. Despite that the matching of both methods is not exactly the same, both classification systems provide simple, reliable and comparable results. PMID- 22038837 TI - Myofibroblast-derived PDGF-BB promotes Hedgehog survival signaling in cholangiocarcinoma cells. AB - Cholangiocarcinoma (CCA) cells paradoxically express the death ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and, therefore, are dependent upon potent survival signals to circumvent TRAIL cytotoxicity. CCAs are also highly desmoplastic cancers with a tumor microenvironment rich in myofibroblasts (MFBs). Herein, we examine a role for MFB-derived CCA survival signals. We employed human KMCH-1, KMBC, HuCCT-1, TFK-1, and Mz-ChA-1 CCA cells, as well as human primary hepatic stellate and myofibroblastic LX-2 cells, for these studies. In vivo experiments were conducted using a syngeneic rat orthotopic CCA model. Coculturing CCA cells with myofibroblastic human primary hepatic stellate cells or LX-2 cells significantly decreased TRAIL-induced apoptosis in CCA cells, a cytoprotective effect abrogated by neutralizing platelet-derived growth factor (PDGF)-BB antiserum. Cytoprotection by PDGF-BB was dependent upon Hedgehog (Hh) signaling, because it was abolished by the smoothened (SMO; the transducer of Hh signaling) inhibitor, cyclopamine. PDGF-BB induced cyclic adenosine monophosphate-dependent protein kinase-dependent trafficking of SMO to the plasma membrane, resulting in glioma-associated oncogene (GLI)2 nuclear translocation and activation of a consensus GLI reporter gene-based luciferase assay. A genome-wide messenger RNA expression analysis identified 67 target genes to be commonly up- (50 genes) or down-regulated (17 genes) by both Sonic hedgehog and PDGF-BB in a cyclopamine-dependent manner in CCA cells. Finally, in a rodent CCA in vivo model, cyclopamine administration increased apoptosis in CCA cells, resulting in tumor suppression. CONCLUSIONS: MFB-derived PDGF-BB protects CCA cells from TRAIL cytotoxicity by a Hh-signaling dependent process. These results have therapeutical implications for the treatment of human CCA. PMID- 22038839 TI - Discrepancies between pediatric laboratories in pulmonary function results from healthy children. AB - BACKGROUND: Multi-center research studies that include pulmonary function as an objective outcome are increasingly important in pediatric respiratory medicine. The need for local controls rather than depending on published normative data for lung function remains debatable. AIM: To compare pulmonary function in childhood controls with no respiratory symptoms from three centers in the United Kingdom and ascertain the extent to which current reference equations are appropriate for this population. METHODS: Spirometry, plethysmographic lung volumes, and specific airways resistance (sRaw) were measured within specialized pediatric laboratories in children from three geographical locations throughout the UK (London, Leicester, and Glasgow), using identical equipment, software and standard operating procedures. Results were compared between centers and in relation to recent or commonly used UK pediatric reference values. RESULTS: Pulmonary function was assessed in 94 healthy children (mean (SD) age: 7.7 (0.6) years; 88% white Caucasians; ~30 from each center). There were no significant differences in background demographics or spirometric outcomes when compared between centers. By contrast, statistically significant differences in plethysmographic lung volumes and sRaw were observed between-centers. Significant differences in relation to published reference data for white subjects were noted for FEV(1) in all three centers and occasionally for other lung function measures but the differences from predicted values were small (within +/- 0.5 z-score) and not clinically significant. CONCLUSION: After appropriate inter-laboratory standardization, spirometric measurements in children can be measured in different centers without evidence of systematic differences. However, even after extensive standardization procedures, plethysmographic measures appear more prone to inter-center differences and cannot, at present, be reliably compared across centers without incorporating controls at each location. PMID- 22038840 TI - Toll-like receptor 5 deficiency protects from wasting disease in a T cell transfer colitis model in T cell receptor-beta-deficient mice. AB - BACKGROUND: Toll-like receptor 5 (TLR5) is implicated in the innate and adaptive immune responses that are associated with inflammatory bowel disease (IBD). In humans TLR5 is expressed on CD4(+) T cells and costimulation with flagellin potentiates effector and regulatory T cell responses. The aim of this study was to determine the role of TLR5 in CD4(+) T cell subsets versus other cells in induction of disease in a model of T cell-dependent colitis. METHODS: TLR5 expression on CD4(+) T cells was assessed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Wildtype (WT) or TLR5-deficient (5-/-) CD4(+) T conventional cells (Tconv) and T regulatory cells (Treg) were compared for their ability to induce and suppress T cell transfer colitis, respectively. In addition, the role of TLR5 expression in recipient mice was analyzed. RESULTS: TLR5 is preferentially expressed on mouse Treg compared to Tconv, although expression levels were low. The colitogenic capacity of WT and 5-/- Tconv was found to be similar and Treg from WT or 5-/- donor animals both prevented T cell transfer colitis in TLR-competent hosts. TLR5 deficiency in recipient mice, however, did affect the disease process, as T cell receptor-beta (TCRbeta) 5-/- recipients had decreased weight loss compared to TCRbeta recipient mice when WT Tconv were used. CONCLUSIONS: TLR5 expression on T cells is not required for induction of or protection from T cell-dependent colitis. Expression of TLR5 in non-T cells has a pathogenic role, since TLR5 deficiency in recipient mice protects against weight loss induced by WT T cells. PMID- 22038841 TI - The anatomist Hans Elias: A Jewish German in exile. AB - Hans Elias (1907 to 1985) was an anatomist, an educator, a mathematician, a cinematographer, a painter, and a sculptor. Above all, he was a German of Jewish descent, who had to leave his home country because of the policies of the National Socialist (NS) regime. He spent his life in exile, first in Italy and then in the United States. His biography is exemplary for a generation of younger expatriates from National Socialist Germany who had to find a new professional career under difficult circumstances. Elias was a greatly productive morphologist whose artistic talent led to the foundation of the new science of stereology and made him an expert in scientific cinematography. He struggled hard to fulfill his own high expectations of himself in terms of his effectiveness as a scientist, educator, and politically acting man in this world. Throughout his life this strong-willed and outspoken man never lost his great fondness for Germany and many of its people, while reserving some of his sharpest criticism for fellow anatomists who were active in National Socialist Germany, among them his friend Hermann Stieve, Max Clara, and Heinrich von Hayek. Hans Elias' life is well documented in his unpublished diaries and memoirs, and thus allows fresh insights into a time period when some anatomists were among the first victims of NS policies and other anatomists became involved in the execution of such policies. PMID- 22038842 TI - Pocket card and dedicated feedback session to improve feedback to ward residents: a randomized trial. AB - BACKGROUND: Residents are often dissatisfied with feedback received on the wards, and hospital attendings are often uncomfortable and unskilled at giving feedback. OBJECTIVE: Determine the impact of a pocket card and feedback session on Internal Medicine (IM) residents' perceptions of feedback and attendings' comfort giving feedback. DESIGN: Prospective randomized trial using chi-square analysis. SETTING: Inpatient wards at 1 academic medical center. PARTICIPANTS: One hundred eleven IM residents and 36 attendings. INTERVENTION: We introduced a pocket feedback card, structured around the Accreditation Council for Graduate Medical Education competencies, and a feedback session to guide mid-rotation feedback. Control group attendings received the usual reminder to provide feedback. MEASUREMENTS: Attendings' and residents' survey responses, after the inpatient month, assessing attitudes towards feedback and qualitative interviews with intervention attendings. RESULTS: Intervention residents were more likely than controls to report sufficient and useful feedback from attendings. They reported more feedback regarding skills needing improvement and how to improve their skills (51.3% vs 25.5%, P = 0.02), and felt their clinical (61.5% vs 27.8%, P = 0.001) and professionalism/communication (51.3% vs 29.1%, P = 0.03) skills improved based on this feedback. Intervention attendings, as compared to controls, agreed that residents improved their professionalism/communication skills (76.9% vs 31.1%, P = 0.02) based on feedback. Most intervention attendings found the card and session acceptable and would use both in the future. CONCLUSIONS: A pocket feedback card and dedicated feedback session improved the quantity and quality of feedback delivered to IM residents by their attendings on the inpatient wards. PMID- 22038843 TI - Polymers for anion recognition and sensing. AB - In biological systems, the selective and high-affinity recognition of anionic species is accomplished by macromolecular hosts (anion-binding proteins) that have been "optimized" through evolution. Surprisingly, it is only recently that chemists have systematically attempted to develop anion-responsive synthetic macromolecules for potential applications in medicine, national security, or environmental monitoring. Recent results indicating that unique features of polymeric systems such as signal amplification, multivalency, and cooperative behavior may be exploited productively in the context of anion recognition and sensing are documented. The wide variety of interactions-including Lewis acid/base, ion-pairing, and hydrogen bonding-that have been employed for this purpose is reflected in the structural diversity of anion-responsive macromolecules identified to date. PMID- 22038844 TI - Constipation is associated with incomplete bladder emptying in healthy children. AB - PURPOSE: To investigate the association between constipation and the results of uroflowmetry with post-void residual urine (PVR) tests in healthy children. MATERIALS AND METHODS: We enrolled healthy children aged between 4 and 12 years for evaluation of voiding and defecation function. A parent of children completed the questionnaire, and the children were asked to do uroflowmetry and PVR. Constipation is defined as defecation frequency <= 2 times/week or type 1-2 stool forms on Bristol stool scale. Uroflowmetry curve and PVR were eligible for analysis if voided volume was between 50 ml and expected capacity for age. RESULTS: Totally, 778 children (415 boys and 363 girls) with a mean age of 7.2 +/ 2.2 years were eligible for analysis. The prevalence of constipation was 10.9% by low defecation frequency, and 28.4% by Bristol stool scale, respectively. Regarding the rate of constipation, there were no statistically significant differences between genders. Compared to children without low defecation frequency, constipated children had higher PVR (9.0 vs. 5.9 ml, P = 0.01), higher rate of PVR > 20 ml (17.7% vs. 7.1%, P = 0.01) and lower voiding efficiency (93.2% vs. 94.9%, P = 0.04). Compared to children without type 1-2 Bristol stool, constipated children did not have higher PVR (7.2 ml vs. 5.8 ml, P = 0.10), nor lower voiding efficiency (94.0% vs. 95.0%, P = 0.11). Urgency symptom score and rate of abnormal flow patterns were comparable between children with or without constipation. CONCLUSION: Constipation defined as low defecation frequency was associated with incomplete bladder emptying in healthy children. PMID- 22038845 TI - alpha-Tocopheryloxyacetic acid is superior to alpha-tocopheryl succinate in suppressing HER2-high breast carcinomas due to its higher stability. AB - Breast cancer is the number one neoplastic disease of women, with the HER2-high carcinomas presenting a considerable challenge for efficient treatment. Therefore, a search for novel agents active against this type of cancer is warranted. We tested two vitamin E (VE) analogs, the esterase-hydrolyzable alpha tocopheryl succinate (alpha-TOS) and the non-hydrolyzable ether alpha tocopheryloxyacetic acid (alpha-TEA) for their effects on HER2-positive breast carcinomas using a breast tumor mouse model and breast cancer cell lines. Ultrasound imaging documented that alpha-TEA suppressed breast carcinomas in the transgenic animals more efficiently than found for its ester counterpart. However, both agents exerted a comparable apoptotic effect on the NeuTL breast cancer cells derived from the FVB/N c-neu mice as well as in the human MBA-MD-453 and MCF7HER2-18 cells with high level of HER2. The superior anti-tumor effect of alpha-TEA over alpha-TOS in vivo can be explained by longer persistence of the former in mice, possibly due to the enhanced plasma and hepatic processing of alpha-TOS in comparison to the esterase-non-cleavable alpha-TEA. Indeed, the stability of alpha-TOS in plasma was inferior to that of alpha-TEA. We propose that alpha-TEA is a promising drug efficient against breast cancer, as documented by its effect on experimental HER2-positive breast carcinomas that present a considerable problem in cancer management. PMID- 22038846 TI - Toxicity of aqueous C70-gallic acid suspension in Daphnia magna. AB - The present study assessed the toxic effects of stable aqueous colloidal suspensions of gallic-acid-stabilized C(70) fullerene on Daphnia magna. The suspensions were stabilized through noncovalent surface modification with gallic acid. In addition to whole-organism responses, changes in antioxidative processes in D. magna were quantified. Acute toxicity was observed with 96LC50 for C(70) gallic acid of 0.4 +/- 0.1 mg/L C(70) . Daphnia magna fecundity was significantly reduced in 21-d bioassays at C(70) -gallic aqcid concentrations below quantifiable limits. Antioxidant enzyme activities of glutathione peroxidase and superoxide dismutase as well as lipid peroxidation suggested that exposed organisms experienced oxidative stress. Microscopic techniques used to determine cellular toxicity via apoptosis proved unsuccessful. PMID- 22038847 TI - Protective effects of passively transferred merozoite-specific antibodies against Theileria equi in horses with severe combined immunodeficiency. AB - Theileria equi immune plasma was infused into young horses (foals) with severe combined immunodeficiency. Although all foals became infected following intravenous challenge with homologous T. equi merozoite stabilate, delayed time to peak parasitemia occurred. Protective effects were associated with a predominance of passively transferred merozoite-specific IgG3. PMID- 22038848 TI - Increased frequency of regulatory T cells and T lymphocyte activation in persons with previously treated extrapulmonary tuberculosis. AB - Extrapulmonary tuberculosis may be due to underlying immune compromise. Immunosuppressive regulatory T cells (Treg cells), and CD4(+) T lymphocytes in general, are important in the host immune response to Mycobacterium tuberculosis. We evaluated T lymphocytes from patients after recovery from extrapulmonary tuberculosis, which may reflect conditions before M. tuberculosis infection. A case-control study was conducted among HIV-uninfected adults with previously treated extrapulmonary tuberculosis and 3 sets of controls: (i) subjects with previously treated pulmonary tuberculosis, (ii) close tuberculosis contacts with M. tuberculosis infection, and (iii) close tuberculosis contacts with no infection. Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4(+) CD25(hi) CD127(low) FoxP3(+) cell (Treg cell) and T lymphocyte activation. Both characteristics were compared as continuous variables between groups with the Kruskal-Wallis test. There were 7 extrapulmonary tuberculosis cases, 18 pulmonary tuberculosis controls, 17 controls with M. tuberculosis infection, and 18 controls without M. tuberculosis infection. The median Treg cell proportion was highest among persons with previous extrapulmonary tuberculosis (1.23%) compared to subjects with pulmonary tuberculosis (0.56%), latent M. tuberculosis infection (0.14%), or no M. tuberculosis infection (0.20%) (P = 0.001). The median proportion of CD4(+) T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4(+) T lymphocytes from persons with previous extrapulmonary tuberculosis (0.79%) compared to subjects with pulmonary tuberculosis (0.44%), latent M. tuberculosis infection (0.14%), or no M. tuberculosis infection (0.32%) (P = 0.005). Compared with controls, persons with previously treated extrapulmonary tuberculosis had the highest Treg cell frequency, but also the highest levels of CD4(+) T lymphocyte activation. Immune dysregulation may be a feature of individuals at risk for extrapulmonary tuberculosis. PMID- 22038849 TI - Maintenance of immune response throughout childhood following serogroup C meningococcal conjugate vaccination in early childhood. AB - The objectives of this study were to evaluate the kinetics of antibody decline through childhood in a longitudinal study of a single cohort following serogroup C meningococcal (MenC) vaccine immunization in early childhood and to calculate the proportion of 11 to 13 year olds with protective levels of bactericidal antibody 10 years after immunization. United Kingdom children aged 11 to 13 years in 2010 who had previously taken part in a longitudinal study at the Oxford Vaccine Group had blood samples drawn between 2001 and 2010. Sera from each time point were analyzed for the MenC serum bactericidal antibody titer using a baby rabbit complement (rSBA) assay. The median age at MenC immunization was 21 months (range, 1 year 3 months to 3 years 9 months). The MenC rSBA geometric mean titer (GMT) at age 3.5 to 5 years was 8.0 (95% confidence interval, 6.5 to 9.9; n = 287). By age 11.5 to 13.5 years, the rSBA GMT had declined to 3.3 (2.5 to 4.4; n = 98). The percentage of children with rSBA titers of >=1:8 (the threshold for protection) also declined from 38% (35% to 41%) to 15% (12% to 19%). We concluded that MenC rSBA titers wane rapidly following vaccination in early childhood and continue to decline into the second decade of life. Since nasopharyngeal colonization in adolescents probably provides the major reservoir for MenC in the population, declining immunity in this cohort is of concern. Sustaining high levels of antibody through booster vaccination in this cohort is likely necessary to avoid a resurgence of disease in the decade ahead. PMID- 22038850 TI - Serum antibody responses to 10 Mycobacterium tuberculosis proteins, purified protein derivative, and old tuberculin in natural and experimental tuberculosis in rhesus monkeys. AB - Old tuberculin (OT) and purified protein derivative (PPD) are widely used for tuberculin skin testing (TST) in diagnosis of tuberculosis (TB) but often yield poor specificity and anergy in reaction. Therefore, it is necessary to develop new serological methods as a possible auxiliary diagnostic method for TB. In this study, we characterized the dynamic antibody responses of 10 purified recombinant antigens, PPD, and OT in rhesus monkeys experimentally infected with Mycobacterium tuberculosis and analyzed the time to antibody detection, antibody levels, and their association with the infectious doses. The antibodies were detected as early as 4 weeks after infection in response to 5 antigens (CFP10, CFP10-ESAT-6, U1, MPT64, and Ag85b). Antibodies against most of the other antigens were detected between 4 and 12 weeks after infection. The levels of antibodies were dose dependant. We further evaluated the serodiagnostic potential of these antigens by using indirect enzyme-linked immunosorbent assay in 71 TST positive and 90 TST-negative serum samples from monkeys. For all 12 antigens, the median optical density values of TST-positive monkeys were statistically significantly higher than those of TST-negative monkeys (P < 0.001). Among those antigens, Ag85b and CFP10 showed higher diagnostic potential than others. A combination of results from Ag85b, the 38-kDa antigen (Ag38kDa), and Ag14kDa reaches a sensitivity of 95.77%, indicating that these antigens may be ideal cocktails in TB diagnosis. PMID- 22038851 TI - Determination of some organophosphorus pesticides in water and watermelon samples by microextraction prior to high-performance liquid chromatography. AB - A novel method based on simultaneous liquid-liquid microextraction and carbon nanotube reinforced hollow fiber microporous membrane solid-liquid phase microextraction has been developed for the determination of six organophosphorus pesticides, i.e. isocarbophos, phosmet, parathion-methyl, triazophos, fonofos and phoxim, in water and watermelon samples prior to high-performance liquid chromatography (HPLC). Under the optimum conditions, the method shows a good linearity within a range of 1-200 ng/mL for water samples and 5-200 ng/g for watermelon samples, with the correlation coefficients (r) varying from 0.9990 to 0.9997 and 0.9986 to 0.9995, respectively. The limits of detection (LODs) were in the range between 0.1 and 0.3 ng/mL for water samples and between 1.0 and 1.5 ng/g for watermelon samples. The recoveries of the method at spiking levels of 5.0 and 50.0 ng/mL for water samples were between 85.4 and 100.8%, and at spiking levels of 5.0 and 50.0 ng/g for watermelon samples, they were between 82.6 and 92.4%, with the relative standard deviations (RSDs) varying from 4.5-6.9% and 5.2 7.4%, respectively. The results suggested that the developed method represents a simple, low-cost, high analytes preconcentration and excellent sample cleanup procedure for the determination of organophosphorus pesticides in water and watermelon samples. PMID- 22038852 TI - Sparsomycin-linezolid conjugates can promote ribosomal translocation. AB - Sparsomycin is an antibiotic that targets the peptidyl transferase center of the ribosome and has the ability to promote ribosomal translocation in the absence of EF-G and GTP. Here we show that changes in the configurations at the two chiral centers of sparsomycin, especially at the chiral carbon, can greatly affect its capability to promote ribosomal translocation. More importantly, the incorporation of the pseudo-uracil moiety of sparsomycin into linezolid through a covalent linkage conferred on linezolid derivatives the ability to promote translocation, thus indicating the importance of interactions between this pseudo uracil moiety, rRNA, and tRNA for promoting translocation. In addition, these translocation promoters can also effectively inhibit spontaneous reverse translocation; this suggests that they might promote forward translocation by trapping the ribosome in the post-translocation state and shifting the equilibrium between the pre- and post-translocation ribosome in the forward direction. PMID- 22038853 TI - The asbestos disease epidemic: here today, here tomorrow. PMID- 22038854 TI - Improving fatty acid production in Escherichia coli through the overexpression of malonyl coA-acyl carrier protein transacylase. AB - The microbial biosynthesis of free fatty acid, which can be used as precursors for the production of fuels or chemicals from renewable carbon sources, has attracted significant attention in recent years. Free fatty acids can be produced by introducing an acyl-carrier protein (ACP) thioesterase (TE) gene into Escherichia coli. The first committed step of fatty acid biosynthesis is the conversion of acetyl-CoA to malonyl-CoA by an adenosine triphosphate (ATP) dependent acetyl-CoA carboxylase followed by the conversion of malonyl-CoA to malonyl-ACP through the enzyme malonyl CoA-acyl carrier protein transacylase (MCT; FabD). The E. coli fabD gene encoding MCT has been cloned and studied. However, the effect of FabD overexpression in a fatty acid overproducing strain has not been examined. In this study, we examined the effect of FabD overexpression in a fatty acid overproducing strain carrying an acyl-ACP TE. Specifically, the effect of overexpressing a fabD gene from four different organisms on fatty acid production was compared. The strains carrying a fabD gene from E. coli, Streptomyces avermitilis MA-4680, or Streptomyces coelicolor A3(2) improved the free fatty acid production; these three strains produced more free fatty acids, about 11% more, than the control strain. The strain carrying a fabD gene from Clostridium acetobutylicum ATCC 824, however, produced similar quantities of free fatty acids as the control strain. In addition, the three FabD overexpressed strains also have higher fatty acid/glucose yields. The results suggested that FabD overexpression can be used to improve free fatty acid production by increasing the malonyl-ACP availability. PMID- 22038856 TI - No association between miso soup intake and female urinary incontinence. PMID- 22038857 TI - Recommendations for the treatment of Crohn's disease with tumor necrosis factor antagonists: an expert consensus report. AB - BACKGROUND: Symptom relief is the traditional treatment goal in Crohn's disease (CD). New goals including mucosal healing and bowel preservation are now achievable with tumor necrosis factor (TNF) antagonists. Infliximab and adalimumab are approved as second-line treatments for severe, active CD. Certolizumab pegol is approved only in the U.S. and Switzerland as second-line treatment for moderate-to-severe, active CD. Data from trials of infliximab suggest that high-risk patients and patients with active inflammation (CRP elevation and/or ileocolonic ulcers) may benefit from earlier use of this drug. METHODS: A Delphi survey was used to obtain consensus on issues surrounding bowel preservation and use of TNF antagonists. At the time of this survey, infliximab was the only TNF antagonist approved for the treatment of CD in Europe, Canada, and Australia. An expert panel of 12 gastroenterologists with substantial clinical experience using infliximab in clinical practice and trials in these areas participated. RESULTS: The experts agreed that bowel preservation and mucosal healing are relevant and achievable goals, and form a rationale for using TNF antagonists in CD patients. Control of inflammation and induction of mucosal healing were considered essential for bowel preservation. Consensus areas: 1) mucosal healing is predictive of improved long-term disease course and increases the likelihood of steroid-free remission; 2) infliximab induces sustained mucosal healing, promotes bowel preservation, and reduces hospitalizations and surgeries; 3) benefits of infliximab in relation to mucosal healing, bowel preservation, and clinical remission increase when therapy is initiated earlier. CONCLUSIONS: Treatment with TNF antagonists helps preserve the bowel in CD patients. PMID- 22038858 TI - The right inferior phrenic artery: path of its ascending branch at the vena caval foramen. AB - The ascending branch of the right inferior phrenic artery is generally understood to pass to the lateral side of the vena caval foramen, on the inferior surface of the diaphragm. A study of 16 cadavers shows that the artery may pass through the vena caval foramen to run on the superior surface of the diaphragm, before returning to the inferior surface by passing through the muscle of the diaphragm. PMID- 22038859 TI - Predicting antibiotic resistance to community-acquired pneumonia antibiotics in culture-positive patients with healthcare-associated pneumonia. AB - OBJECTIVE: To develop and validate a model to predict resistance to community acquired pneumonia antibiotics (CAP-resistance) among patients with healthcare associated pneumonia (HCAP), and to compare the model's predictive performance to a model including only guideline-defined criteria for HCAP. DESIGN: Retrospective cohort study. SETTING: Six Veterans Affairs Medical Centers in the northwestern United States. PATIENTS: Culture-positive inpatients with HCAP. MEASUREMENTS: Patients were identified based upon guideline-defined criteria for HCAP. Relevant cultures obtained within 48 hours of admission were assessed to determine bacteriology and antibiotic susceptibility. Medical records for the year preceding admission were assessed to develop predictive models of CAP-resistance with logistic regression. The predictive performance of cohort-developed and guideline-defined models was compared. RESULTS: CAP-resistant organisms were identified in 118 of 375 culture-positive patients. Of guideline-defined criteria, CAP-resistance was associated (odds ratio (OR) [95% confidence interval (CI)]) with: admission from nursing home (2.6 [1.6-4.4]); recent antibiotic exposure (1.7 [1.0-2.8]); and prior hospitalization (1.6 [1.0-2.6]). In the cohort-developed model, CAP-resistance was associated with: admission from nursing home or recent nursing home discharge (2.3 [1.4-3.8]); positive methicillin-resistant Staphylococcus aureus (MRSA) history within 90 days of admission (6.4 [2.6-17.8]) or 91-365 days (2.3 [0.9-5.9]); cephalosporin exposure (1.8 [1.1-2.9]); recent infusion therapy (1.9 [1.0-3.5]); diabetes (1.7 [1.0 2.8]); and intensive care unit (ICU) admission (1.6 [1.0-2.6]). Area under the receiver operating characteristic curve (aROC [95% CI]) for the cohort-developed model (0.71 [0.65-0.77]) was significantly higher than for the guideline-defined model (0.63 [0.57-0.69]) (P = 0.01). CONCLUSIONS: Select guideline-defined criteria predicted CAP-resistance. A cohort-developed model based primarily on prior MRSA history, nursing home residence, and specific antibiotic exposures provided improved prediction of CAP-resistant organisms in HCAP. PMID- 22038860 TI - Survival in patients with human papillomavirus positive tonsillar cancer in relation to treatment. AB - The incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases have increased in the last decades. In parallel, treatment for tonsillar cancer has been intensified e.g., by accelerated radiotherapy, and chemotherapy, resulting in more side effects. Patients with HPV-positive tonsillar cancer have better prognosis than those with HPV-negative tumors, and the former group could hypothetically benefit from reduced, less-toxic treatment without compromising survival. Here, we therefore evaluated possible differences in overall and disease-specific survival after different oncological treatments in 153 patients with HPV DNA- and P16-positive tonsillar cancer who were diagnosed and treated with intent to cure between 2000 and 2007, in Stockholm, Sweden. Of these patients, 86 were treated with conventional radiotherapy, 40 were treated with accelerated radiotherapy and 27 were treated with chemoradiotherapy. There were no significant differences in overall or disease-free survival between the groups. However, there was a trend, implying a beneficial effect of the intensified treatment, with chemoradiotherapy being better than radiotherapy despite that more patients had stage IV disease in the former group; and accelerated radiotherapy being better than conventional radiotherapy. This needs to be followed further in larger more homogenous groups of patients. In conclusion, patients with HPV-positive tonsillar cancer treated with conventional- or accelerated radiotherapy or chemoradiotherapy disclosed similar survival rates. The trend for better survival and less metastasis after intensified treatment underlines the need for large prospective studies comparing less intense to more intense treatment (chemoradiotherapy). PMID- 22038861 TI - Interactions of gold nanoparticles with freshwater aquatic macrophytes are size and species dependent. AB - The partitioning of 4- and 18-nm gold nanoparticles (AuNPs) to aquatic macrophytes was investigated in vivo with exposure suspension in well water. Three morphologically distinct aquatic macrophytes were studied. Myriophyllum simulans Orch. and Egeria densa Planch. are submerged aquatic vascular plants, whereas Azolla caroliniana Willd. is a free-floating aquatic fern. Because aquatic plants absorb the majority of their nutrients from the water column, it is logical to hypothesize that they may absorb nanomaterials in suspension, potentially facilitating trophic transfer. Each plant was exposed to two different-sized gold nanospheres at a nominal concentration of 250 ug/L AuNPs for 24 h. Macrophytes were harvested at six time points (1, 3, 6, 12, 18, and 24 h), dried, and then analyzed for gold concentration via inductively coupled plasma mass spectrometry. Concentrations were normalized to whole-plant dry tissue mass. The present study shows that absorption of AuNPs through root uptake was size and species dependent. Electron microscopy revealed that 4- and 18-nm AuNPs adsorbed to the roots of each species. Root tissue was sectioned, and transmission electron microscopy indicated that 4-nm and 18-nm AuNPs were absorbed by A. caroliniana, whereas only 4-nm AuNPs were absorbed by M. simulans. Egeria densa did not absorb AuNPs of either size. Gold nanoparticles were confirmed in tissue by using energy-dispersive X-ray spectroscopy. Absorption of AuNPs by plants may be a function of the salinity tolerance of each species. PMID- 22038862 TI - Proteomic analysis of Col11a1-associated protein complexes. AB - Cartilage plays an essential role during skeletal development within the growth plate and in articular joint function. Interactions between the collagen fibrils and other extracellular matrix molecules maintain structural integrity of cartilage, orchestrate complex dynamic events during embryonic development, and help to regulate fibrillogenesis. To increase our understanding of these events, affinity chromatography and liquid chromatography/tandem mass spectrometry were used to identify proteins that interact with the collagen fibril surface via the amino terminal domain of collagen alpha1(XI) a protein domain that is displayed at the surface of heterotypic collagen fibrils of cartilage. Proteins extracted from fetal bovine cartilage using homogenization in high ionic strength buffer were selected based on affinity for the amino terminal noncollagenous domain of collagen alpha1(XI). MS was used to determine the amino acid sequence of tryptic fragments for protein identification. Extracellular matrix molecules and cellular proteins that were identified as interacting with the amino terminal domain of collagen alpha1(XI) directly or indirectly, included proteoglycans, collagens, and matricellular molecules, some of which also play a role in fibrillogenesis, while others are known to function in the maintenance of tissue integrity. Characterization of these molecular interactions will provide a more thorough understanding of how the extracellular matrix molecules of cartilage interact and what role collagen XI plays in the process of fibrillogenesis and maintenance of tissue integrity. Such information will aid tissue engineering and cartilage regeneration efforts to treat cartilage tissue damage and degeneration. PMID- 22038863 TI - Synthetic small molecules for epigenetic activation of pluripotency genes in mouse embryonic fibroblasts. AB - Considering the essential role of chromatin remodeling in gene regulation, their directed modulation is of increasing importance. To achieve gene activation by epigenetic modification, we synthesized a series of pyrrole-imidazole polyamide conjugates (PIPs) that can bind to predetermined DNA sequences, and attached them with suberoylanilide hydroxamic acid (SAHA), a potent histone deacetylase inhibitor. As histone modification is associated with pluripotency, these new types of conjugates, termed SAHA-PIPs, were screened for their effect on the expression of induced pluripotent stem cell (iPSC) factors. We found certain SAHA PIPs that could differentially up-regulate the endogenous expression of Oct-3/4, Nanog, Sox2, Klf4 and c-Myc. SAHA and other SAHA-PIPs did not show such induction; this implies a role for PIPs and their sequence specificity in this differential gene activation. Chromatin immunoprecipitation analysis suggested that SAHA-PIP-mediated gene induction proceeds by histone H3 Lys9 and Lys14 acetylation and Lys4 trimethylation, which are epigenetic features associated with transcriptionally active chromatin. PMID- 22038864 TI - Effects of ptb knockout on butyric acid fermentation by Clostridium tyrobutyricum. AB - Clostridium tyrobutyricum ATCC 25755 is an anaerobic, rod-shaped, gram-positive bacterium that produces butyrate, acetate, hydrogen, and carbon dioxide from various saccharides, including glucose and xylose. Phosphotransbutyrylase (PTB) is a key enzyme in the butyric acid synthesis pathway. In this work, effects of ptb knockout by homologous recombination on metabolic flux and product distribution were investigated. When compared with the wild type, the activities of PTB and butyrate kinase in ptb knockout mutant decreased 76 and 42%, respectively; meanwhile, phosphotransacetylase and acetate kinase increased 7 and 29%, respectively. However, ptb knockout did not significantly reduce butyric acid production from glucose or xylose in batch fermentations. Instead, it increased acetic acid and hydrogen production 33.3-53.8% and ~ 11%, respectively. Thus, the ptb knockout did increase the carbon flux toward acetate synthesis, resulting in a significant decrease (28-35% reduction) in the butyrate/acetate ratio in ptb mutant fermentations. In addition, the mutant displayed a higher specific growth rate (0.20 h(-1) vs. 0.15 h(-1) on glucose and 0.14 h(-1) vs. 0.10 h(-1) on xylose) and tolerance to butyric acid. Consequently, batch fermentation with the mutant gave higher fermentation rate and productivities (26 48% increase for butyrate, 81-100% increase for acetate, and 38-46% increase for hydrogen). This mutant thus can be used more efficiently than the parental strain in fermentations to produce butyrate, acetate, and hydrogen from glucose and xylose. PMID- 22038865 TI - Histological discrimination between autoimmune hepatitis and drug-induced liver injury. PMID- 22038866 TI - Transcriptome analyses of Populus x euramericana clone I-214 leaves exposed to excess zinc. AB - Zinc (Zn) is an essential element for plant growth and development, but at high levels this metal can become toxic. Hyperaccumulator species are often not suitable for phytoremediation technologies because they need to be fast growing and have high biomass production, such as those of the Populus genus. Comparative genomics studies of poplars subjected to stress conditions such as heavy metal contamination have generated resources useful for improving the annotation of genes and have provided novel insights in the defense/tolerance mechanisms governing adaptation in non-hyperaccumulator plants. Using a microarray-based comparative analysis, we identified functional gene sets that are differentially regulated in the leaves of Populus * euramericana clone I-214 subjected to an excess but sub-lethal dose of Zn (1 mM). Eco-physiological and chemical analyses confirmed the results obtained in previous similar experiments. A total of 3861 expressed sequence tags (ESTs) were differentially expressed and grouped into two distinct libraries of up-regulated (40%) and down-regulated (60%) putative genes. The annotation of genes and gene products according to the Gene Ontology vocabularies was performed using Blast2GO software. The two transcriptome data sets were used to query all known Kyoto Encyclopedia of Genes and Genomes (KEGG) biosynthetic pathways of the genes identified in this study. The most represented molecular functions and biological processes were nucleotide binding and transcription, transport and response to stress and abiotic and biotic stimuli. The chloroplast, mitochondrion and their membrane systems were the cellular components most affected by excess Zn, as well as the photosynthetic, defense, sulfur and glutathione (GSH) metabolic pathways. The most up-regulated genes encoded electron carriers associated with ferrodoxin, the small subunit of ribulose-bisphosphate carboxylase oxygenase, and enzymes involved in GSH metabolism. This study is the most in-depth transcriptome and gene-annotation analysis of a hybrid poplar to date. The results are presented and critically discussed in terms of poplar response/tolerance to Zn stress for the characterization of non-hyperaccumulator phenotypes and the identification of candidate genes in perennial plants. These genetic findings provide useful information on tree species' adaptation to metal stress and provide powerful tools for the selection and/or genetic manipulation of stress-tolerant poplar clones. PMID- 22038867 TI - Visitor effects on the behavior of captive Western lowland gorillas: the importance of individual differences in examining welfare. AB - Given the conflicting and somewhat limited findings available on the effect of zoo visitors on primate behavior, the primary purpose of this study was to provide additional data on gorillas' response to variations in crowd size and to look at what other factors-both intrinsic (e.g. personality, sex, and rearing history) and extrinsic (e.g. group)-might influence such responses. Subjects included four groups (three mixed-sex and one bachelor) of captive western lowland gorillas living at Zoo Atlanta. Overall activity budgets and rates of social behaviors in high and low crowd conditions were compared. Behaviors suggestive of general welfare did not vary as a function of crowd size alone, although we did observe one significant interaction and several trends. Specifically, two groups spent more time engaged in undesirable behaviors in the high crowd condition, whereas the other two groups showed the opposite response pattern. Additionally, males, but not females, showed a trend toward greater rates of contact aggression in the high crowd condition, although wounding rates did not vary with crowd size. We also found trends towards variation in response to crowd size as a function of individual personality ratings. These results suggest that although the visitor effect may constitute an impediment to optimal animal welfare, this may only apply to some individuals or groups. We emphasize the importance of continuing to explore individual differences and the limitations of a one-size-fits-all approach when describing influences on animal welfare. PMID- 22038868 TI - Treatment of breast adenocarcinoma metastasis to the neck: dedifferentiation of the tumor as suggested by hormone markers. AB - BACKGROUND: Breast carcinoma rarely metastasizes to the neck, and its management in this area is controversial. There is little published data about whether hormone receptor status changes between primary breast tumors and neck metastasis and whether this influences management. METHODS: We evaluated the demographics and treatment of 13 patients presenting with neck metastasis. We used immunochemistry to assess estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 in the primary and metastatic neck nodes. RESULTS: Hormone receptor status changed in some patients (23% for estrogen receptor, and 31% for progesterone receptor). Three patients had complete excision of their neck disease and subsequent good local control. None of our patients survived despite treatment. CONCLUSION: The change in hormone status could suggest tumor dedifferentiation. Surgical resection, where possible, achieves good local control for these patients, but, because survival is poor, it is only recommended when it results in little significant morbidity. PMID- 22038869 TI - Nasal reconstruction. AB - The nose is the central feature that defines one's face. Acquired nasal defects arise from a variety of pathologic and traumatic etiologies and reconstructive surgeons may be called upon to restore form and function when the nose has been altered in some way. Nasal reconstruction is one of the most challenging and rewarding procedures performed by the plastic surgeon. A detailed knowledge of the anatomy of the nose - the lining, support and cover - is essential in designing the reconstructive effort. Surgical planning involves, first, identifying the extent of the acquired defect, followed by the application of an intricate knowledge of the tissues that will provide a functional and aesthetically pleasing yet durable reconstruction. In this article, the reader will find a description of the clinically important anatomic features of the nose as they relate to various reconstructive procedures aimed at restoring nasal appearance and maintaining airway patency. PMID- 22038870 TI - Food-frequency questionnaire-based estimates of total antioxidant capacity and risk of non-Hodgkin lymphoma. AB - Antioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non-Hodgkin lymphoma (NHL). The oxygen radical absorbance capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food-frequency questionnaire (FFQ). We tested the hypothesis that higher intake of antioxidant nutrients from foods, supplements and FFQ-based ORAC values are associated with a lower risk of NHL in a clinic-based study of 603 incident cases and 1,007 frequency-matched controls. Diet was assessed with a 128-item FFQ. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals adjusted for age, sex, residence and total energy. Dietary intake of alpha tocopherol (OR=0.50; p-trend=0.0002), beta-carotene (OR=0.58; p-trend=0.0005), lutein/zeaxanthin (OR=0.62; p-trend=0.005), zinc (OR=0.54; p-trend=0.003) and chromium (OR=0.68; p-trend=0.032) was inversely associated with NHL risk. Inclusion of supplement use had little impact on these associations. Total vegetables (OR=0.52; p-trend<0.0001), particularly green leafy (OR=0.52; p trend<0.0001) and cruciferous (OR=0.68; p-trend=0.045) vegetables, were inversely associated with NHL risk. NHL risk was inversely associated with both hydrophilic ORAC (OR=0.61, p-trend=0.003) and lipophilic ORAC (OR=0.48, p-trend=0.0002), although after simultaneous adjustment for other antioxidants or total vegetables, only the association for lipophilic ORAC remained significant. There was no striking heterogeneity in results across the common NHL subtypes. Higher antioxidant intake as estimated by the FFQ-ORAC, particularly the lipophilic component, was associated with a lower NHL risk after accounting for other antioxidant nutrients and vegetable intake, supporting this as potentially useful summary measure of total antioxidant intake. PMID- 22038871 TI - Differentiating Crohn's disease from intestinal tuberculosis using an interferon gamma release assay. PMID- 22038872 TI - Inpatient staffing within pediatric residency programs: work hour restrictions and the evolving role of the pediatric hospitalist. AB - OBJECTIVE: In October 2010, the Accreditation Council for Graduate Medical Education (ACGME) mandated new standards that will further restrict resident work hours. There is growing concern surrounding the impact these restrictions will have on the staffing of inpatient services. The objective of this study was to survey the landscape of pediatric resident coverage of noncritical care inpatient teaching services prior to the implementation of these guidelines. In addition, we sought to explore how changes in work hour restrictions might affect the role of pediatric hospitalists in training programs. METHODS: In January 2010, an institutional review board (IRB)-approved electronic survey was sent to 196 US residency training programs via the Association of Pediatric Program Directors (APPD) listserve. RESULTS: One hundred twenty responses were received representing 5201 pediatric residents. Of the programs that responded, 84% have hospitalists. At programs with hospitalists (n = 97), 24% have pediatric hospitalist attendings in-house at night. Nearly a quarter of responding programs (22%) reported having no attending physicians in-house at night. At the time of our survey, 31% of programs anticipated the addition of 24-hour in-house hospitalist coverage within the next 5 years. When the additional work hour restrictions are implemented, 70% of programs anticipated the need to add additional hospitalist coverage at night. CONCLUSIONS: Significant variation exists in how pediatric teaching services provide overnight coverage. While hospitalists are prevalent in pediatric training programs (84% overall, 67% day only), their role in direct patient care during the overnight hours has been limited thus far. New work hour restrictions will promote the need for more hospitalists. PMID- 22038873 TI - Magnetic resonance and Mossbauer studies of superparamagnetic gamma-Fe2O3 nanoparticles encapsulated into liquid-crystalline poly(propylene imine) dendrimers. AB - We present the first results of electron magnetic resonance (EMR) and Mossbauer spectroscopy studies of gamma-Fe(2)O(3) nanoparticles (NPs) incorporated into liquid-crystalline, second-generation dendrimers. The mean size of NPs formed in the dendrimers was around 2.5 nm. A temperature-driven transition from superparamagnetic to ferrimagnetic resonance was observed for the sample. Low temperature blocking of the NP magnetic moments has been clearly evidenced in the integrated EMR line intensity and the blocking temperature was about 60 K. The physical parameters of magnetic NPs (magnetic moment, effective magnetic anisotropy) have been determined from analyses of the EMR data. The effective magnetic anisotropy constant is enhanced relative to bulk gamma-Fe(2)O(3) and this enhanced value is associated with the influence of the surface and shape effects. The angular dependence of the EMR signal position for the field-freezing sample from liquid-crystalline phase showed that NPs possessed uniaxial anisotropy, in contrast to bulk gamma-Fe(2)O(3). Mossbauer spectroscopy determined that fabricated NPs consisted of an alpha-Fe core and a gamma Fe(2)O(3) shell. PMID- 22038874 TI - A statistical selection strategy for normalization procedures in LC-MS proteomics experiments through dataset-dependent ranking of normalization scaling factors. AB - Quantification of LC-MS peak intensities assigned during peptide identification in a typical comparative proteomics experiment will deviate from run-to-run of the instrument due to both technical and biological variation. Thus, normalization of peak intensities across an LC-MS proteomics dataset is a fundamental step in pre-processing. However, the downstream analysis of LC-MS proteomics data can be dramatically affected by the normalization method selected. Current normalization procedures for LC-MS proteomics data are presented in the context of normalization values derived from subsets of the full collection of identified peptides. The distribution of these normalization values is unknown a priori. If they are not independent from the biological factors associated with the experiment the normalization process can introduce bias into the data, possibly affecting downstream statistical biomarker discovery. We present a novel approach to evaluate normalization strategies, which includes the peptide selection component associated with the derivation of normalization values. Our approach evaluates the effect of normalization on the between-group variance structure in order to identify the most appropriate normalization methods that improve the structure of the data without introducing bias into the normalized peak intensities. PMID- 22038875 TI - Responses of chimpanzees to a recently dead community member at Gombe National Park, Tanzania. AB - Chimpanzee responses to the death of a group member have rarely been observed in the wild and most instances involve infant deaths. One of the very few detailed accounts of a group's response to the death of an adult community member is from Gombe National Park, Tanzania, where Teleki [Folia Primatologica 20:81-94, 1973] observed the responses of 16 chimpanzees to an accidental death, none of whom touched the body. Now, almost 40 years later, we report on the behaviors of 16 (different) Gombe individuals to the recently dead body of an adult female community member. In stark contrast to Teleki's account, we observed individual chimpanzees' responses to range from curious observation and passive investigation (e.g. smelling and grooming) to the shaking, dragging, and frustrated beating of the body. Variation across demographic groups is described and may reflect individuals' past experience with death. The implications of our observations are discussed in the context of core morbidity traits shared between humans and chimpanzees. PMID- 22038876 TI - Adjunct therapeutic plasma exchange for anti-N-methyl-D-aspartate receptor antibody encephalitis: a case report and review of literature. AB - Encephalitis associated with autoantibodies directed against the N-methyl-D aspartate receptor (NMDAR) is usually a paraneoplastic syndrome that presents in young females with ovarian teratomas. We report a case of a previously healthy 14 year-old girl with sudden-onset paranoia, hallucinations, hyperactivity, increased speech, decreased sleep, seizures, and violent behavior deteriorating to catatonia. Her cerebrospinal fluid tested positive for anti-NMDAR antibodies. She was treated with five sessions of therapeutic plasma exchange (TPE) after having failed therapy with antibiotics, intravenous steroids, intravenous immunoglobulin (IVIG), one dose of rituximab, and seven sessions of electroconvulsive therapy (ECT). The American Society for Apheresis assigns a Category III (Grade 2C) recommendation for TPE in paraneoplastic neurologic syndromes; however, apheresis specifically for anti-NMDAR encephalitis has not been well studied. Literature review revealed two case reports describing outstanding improvement in patients with anti-NMDAR encephalitis following TPE. We report no improvement in our patient's symptoms after plasma exchange and discuss possible reasons for why it failed along with review of the literature. PMID- 22038877 TI - Simultaneous left maxillary and right mandibular reconstructions with a split osteomyocutaneous peroneal artery-based combined flap. AB - BACKGROUND: Traditionally, reconstruction of concurrent maxillary and mandibular defects on opposite sides of the facial skeleton often requires use of 2 free osseocutaneous flaps. A new technique of using a differentially split osteomyocutaneous peroneal artery-based combined (OPAC) flap for 1-stage reconstruction of left maxillary and right mandibular defects is presented. METHODS: An OPAC flap with 1 skin paddle and a cuff of soleus muscle was harvested. The fibula was split; the distal osseous flap was used for right mandibular reconstruction, and the proximal OPAC flap composing of proximal fibula, skin paddle, and soleus muscle was used for the maxillary reconstruction. Bilateral facial vessels were used as recipient vessels. RESULTS: No complications were encountered. The patient showed good functional and cosmetic outcomes at 1-year follow-up. CONCLUSION: The split OPAC flap allows for simultaneous reconstruction of bony defects that are spatially far apart without the need for a second free flap. PMID- 22038878 TI - Accessory head of flexor pollicis longus muscle in fetuses and adult cadavers and its relation to anterior interosseous nerve. AB - This study was conducted to examine the accessory head of flexor pollicis longus muscle (ahFPL) and its relation with the anterior interosseous nerve (AIN) in human fetuses and adult cadavers. Ninety fetus forearms and 52 adult cadaver forearms were dissected to evaluate the incidence, morphology, and innervation of the ahFPL. The ahFPL was observed in 29/90 (32%) of the fetus forearms and 20/52 (39%) of the adult cadaver forearms. The overall side incidence was 34.5% (49/142) among total forearms examined. On the other hand, the population incidence of ahFPL was 42% (19/45) in fetuses while it was 50% (12/24) in adult cadavers. So, the overall incidence in humans was 44.9% (31/69) in the population studied. Compression of the AIN in the forearm by the ahFPL is known as one of the causes of the anterior interosseous nerve syndrome (AINS). So, the relation of ahFPL with the AIN was evaluated, and in light of previous classifications a modified new classification is proposed. The most common relation detected in this study was Type IVa (71.4%) (AIN and its branches coursed posterior to the ahFPL). While Type I was not observed in this study, the incidences of Type II, Type III, and Type IVb (all AIN branches 'without AIN itself' coursed posterior to the ahFPL) were 2%, 14.3%, and 12.3%, respectively. The Types I, IVa, and IVb are thought to be associated with complete or incomplete types of AINS and Type III with incomplete type of AINS only. PMID- 22038879 TI - Adverse outcomes associated with delayed intensive care unit transfers in an integrated healthcare system. AB - BACKGROUND: Patients with intensive care unit (ICU) transfers from hospital wards have higher mortality than those directly admitted from the emergency department. OBJECTIVE: To describe the association between the timing of unplanned ICU transfers and hospital outcomes. DESIGN, SETTING, PATIENTS: Evaluation of 6369 early (within 24 hours of hospital admission) unplanned ICU transfer cases and matched directly admitted ICU controls from an integrated healthcare system. Cohorts were matched by predicted mortality, age, gender, diagnosis, and admission characteristics. Hospital mortality of cases and controls were compared based on elapsed time and diagnosis. RESULTS: More than 5% of patients admitted through the emergency department experienced an unplanned ICU transfer; the incidence and rates of transfers were highest within the first 24 hours of hospitalization. Multivariable matching produced 5839 (92%) case-control pairs. Median length of stay was higher among cases (5.0 days) than controls (4.1 days, P < 0.01); mortality was also higher among cases (11.6%) than controls (8.5%, P < 0.01). Patients with early unplanned transfers were at an increased risk of death (odds ratio, 1.44; 95% confidence interval, 1.26-1.64; P < 0.01); an increased risk of death was observed even among patients transferred within 8 hours of hospitalization. Hospital mortality differed based on admitting diagnosis categories. While it was higher among cases admitted for respiratory infections and gastrointestinal bleeding, it was not different for those with acute myocardial infarction, sepsis, and stroke. CONCLUSIONS: Early unplanned ICU transfers-even within 8 hours of hospitalization-are associated with increased mortality; outcomes vary by elapsed time to transfer and admitting diagnosis. PMID- 22038880 TI - Can hypopressive exercises provide additional benefits to pelvic floor muscle training in women with pelvic organ prolapse? AB - AIMS: The aim of the study was to compare the effect of hypopressive exercises including pelvic floor muscle contraction, pelvic floor muscle training (PFMT) alone and control on pelvic floor muscle function in women with pelvic organ prolapse (POP). METHODS: Fifty-eight women with a mean age of 55.4 (+/- 9.8) years old with stage II POP were randomly assigned to participate in the PFMT group, the hypopressive exercises associated with PFMT (HE + PFMT) group or the control group. Each treatment group underwent a 3-month course of treatment. The three groups received lifestyle advice regarding weight loss, constipation, coughing, and the avoidance of heavy lifting. Participants were evaluated before and after the treatment. Maximal voluntary contraction (MVC) and endurance were assessed using the Modified Oxford grading system. To evaluate muscle activation, surface electromyography (SEMG) was used. RESULTS: The two treatment group significantly increase pelvic floor muscle function as measured by MVC (P < 0.001) using the Modified Oxford grading system, as well as muscle activation (P < 0.001), measured by SEMG. The PFMT group was superior regarding endurance (P = 0.007). Both groups were superior to the control group regarding MVC, endurance and muscle activation. CONCLUSION: Adding hypopressive exercises to PFMT does not improve PFM function. Both treatment groups performed better than the control group. PMID- 22038881 TI - The role of the pi linker in donor-pi-acceptor organic dyes for high-performance sensitized solar cells. AB - The key elements arising from different linkers between donor (D) and acceptor (A) fragments in D-pi-A organic dyes are computationally studied. Taking triarylamine and the cyanoacrylic acid fragments as donor and acceptor units, respectively, the role of the different separators is computationally explored by means of optimized geometries, frontier molecular orbitals, static polarizabilities and hyperpolarizabilities, excitation energies to the lowest excited singlet, the charge-transfer character of the transition, and simulated absorption spectra. The results are compared to two closely related sets of linkers. Electronic-structure calculations on the studied organic dyes are performed with the CIS(D) wave function based method and time-dependent density functional theory (omegaB97, omegaB97X, and omegaPBEh functionals). Solvation effects are introduced with the polarizable continuum model (PCM). PMID- 22038882 TI - Variations in sexual behavior among capuchin monkeys function for conspecific mate recognition: a phylogenetic analysis and a new hypothesis for female proceptivity in tufted capuchins. AB - Researchers of capuchin monkeys have noted stereotyped body postures, facial expressions, and vocalizations that accompany copulations in this genus. Notable variations in these sexual behaviors are observed across capuchin species. Although several hypotheses exist to explain variation in the duration and vigor of sexual behaviors across species, there is no proposed explanation for variation in the forms of these behaviors. I hypothesized that the forms of sexual behaviors function as recognition signals of conspecific mates. Such signals are adaptive when F1 hybrids exhibit reduced fitness compared with nonhybrid offspring. Recent evidence from nonprimate taxa supports the existence of species recognition signals during mating. Using newly observed sexual behaviors for Cebus albifrons and a recent phylogeny of capuchins, I found significant support for a key prediction of the conspecific mate recognition hypothesis: evolutionary changes in sexual behaviors were associated with speciation. Given the resultant best model for evolution of sexual behaviors, I reconstructed the ancestral pattern of sexual behaviors for extant capuchin species (genera Cebus and Sapajus). This reconstruction suggests that the extreme female proceptivity of tufted capuchin monkeys may function to increase female reproductive choices in the context of sperm-limited males (genus Sapajus). PMID- 22038883 TI - Simultaneous fat suppression and band reduction with large-angle multiple acquisition balanced steady-state free precession. AB - Balanced steady-state free precession (bSSFP) MRI is a rapid and signal-to-noise ratio-efficient imaging method, but suffers from characteristic bands of signal loss in regions of large field inhomogeneity. Several methods have been developed to reduce the severity of these banding artifacts, typically involving the acquisition of multiple bSSFP datasets (and the accompanying increase in scan time). Fat suppression with bSSFP is also challenging; most existing methods require an additional increase in scan time, and some are incompatible with bSSFP band-reduction techniques. This work was motivated by the need for both robust fat suppression and band reduction in the presence of field inhomogeneity when using bSSFP for flow-independent peripheral angiography. The large flip angles used in this application to improve vessel conspicuity and contrast lead to specific absorption rate considerations, longer repetition times, and increased severity of banding artifacts. In this work, a novel method that simultaneously suppresses fat and reduces bSSFP banding artifact with the acquisition of only two phase-cycled bSSFP datasets is presented. A weighted sum of the two bSSFP acquisitions is taken on a voxel-by-voxel basis, effectively synthesizing an off resonance profile at each voxel that puts fat in the stop band while keeping water in the pass band. The technique exploits the near-sinusoidal shape of the bSSFP off-resonance spectrum for many tissues at large (>50 degrees ) flip angles. PMID- 22038884 TI - Homozygosity for the NOD2 p.Leu1007fsX1008 variant is the main genetic predictor for fibrostenotic Crohn's disease. PMID- 22038885 TI - Two-dimensional proteome reference maps for the soybean cyst nematode Heterodera glycines. AB - 2-DE reference maps of Heterodera glycines were constructed. After in-gel digestion with trypsin, 803 spots representing 426 proteins were subsequently identified by LC-MS/MS. Proteins with annotated function were further categorized by Gene Ontology. The results showed that proteins involved in metabolic, developmental and biological regulation processes were the most abundant. PMID- 22038886 TI - Radiolabeled iodohypericin as tumor necrosis avid tracer: diagnostic and therapeutic potential. AB - It is estimated that 30-80% of solid tumor mass represents necrotic tissue that consists out of a significant number of dead and dying cells. The fact that these necrotic zones are restricted to dysplastic and malignant tissue and are rarely present in normal tissue makes necrosis an interesting target both for cancer diagnosis and therapy. In this study, the avidity of hypericin, [(123) I]iodohypericin and [(131) I]iodohypericin to tumor necrosis was explored for both diagnosis and therapy of experimental malignancies. The intratumoral distribution in RIF-1 tumors was investigated by means of fluorescence microscopy (hypericin) and autoradiography ([(123) I]iodohypericin). Results show high uptake of the tracers in necrosis at 24 hr, lasting for up to 72 hr p.i. Ratios of activity of [(123) I]iodohypericin in necrotic tissue over viable tumor reached up to 19.63 +/- 4.66, correlating with 9.20% ID/g in necrosis. Nude mice bearing RIF-1 tumors that received three injections of 300 MUCi over a 3-week treatment period showed stabilization in tumor growth for 5 days, as measured by caliper and micro-positron emission tomography using [(18) F]fluorodeoxyglucose. Based on these results, we suggest the potentials of radiolabeled hypericin (1) in diagnostic aspects including prognosis or staging assessment of bulky necrotic cancers, monitoring of treatments and therapeutic follow-up; and (2) in cancer treatment based on tumor necrosis. In conclusion, we showed that hypericin radiolabeled with iodine is a necrosis avid tracer that can be used both as a tumor diagnostic and therapeutic. PMID- 22038887 TI - Highly selective A(1) -adenosine-agonist (2-chloro-N6-cyclopentyladenosine) and reduction of flap necrosis in adipocutaneous flaps in rats. AB - BACKGROUND: The 2-chloro-N6-cyclopentyladenosine (CCPA) was proven to be a protective factor in ischemic reperfusion injury in myocardium and to reduce the infarct size in the heart. The purpose of this study was to determine whether flap necrosis could be reduced by intravenous administration of CCPA. METHODS: Fifty-six male Wistar rats were divided into 4 experimental groups. An epigastric adipocutaneous flap was raised, and the area of flap necrosis was assessed for all groups on the fifth postoperative day with planimetry software. RESULTS: The control group had a significantly lower rate of flap necrosis than the ischemic control group (p < .05). The nonischemic CCPA group had a significantly lower rate of flap necrosis than the nonischemic control group (p < .05). The ischemic CCPA group had a highly significant (p < .0001) rate of lower flap necrosis than the ischemic control group. CONCLUSION: Our data show that reduction of flap necrosis can be achieved both with and without ischemic periods by intravenous administration of CCPA. PMID- 22038888 TI - Empirical hydrogen-bond potential functions--an old hat reconditioned. AB - The accurate description of hydrogen-bond interactions is of vital importance for the computational modeling of biological systems. Standard force field (FF) as well as semiempirical quantum mechanical (SQM) methods are now known to have considerable problems with the accurate description of hydrogen bonds. It was found that the performance of SQM methods can be greatly improved with empirical hydrogen-bond correction terms. In the first part of this work we review the improvements developed during the recent revival of dedicated hydrogen-bond terms, also in the light of earlier FF-related work. The second part presents new findings connected to open questions in this field, namely, a study on the importance of angular and torsional information, a scheme how to avoid atom-type defined target angles and a reduced version of our DH(+) model for the application to force-field methods and physically motivated protein-ligand scoring functions. Our results highlight the importance of using a complete geometric description (including angular and torsional coordinates) for the accurate treatment of hydrogen bonding. The reduced DH(+) model-applied to a modified version of the UFF force field-shows a much improved accuracy for non covalent interactions also with FF methods, with gains in accuracy by more than one order of magnitude. PMID- 22038889 TI - Genetic evidence for dispersal by both sexes in the Central American Squirrel Monkey, Saimiri oerstedii citrinellus. AB - Sex-biased dispersal (SBD) is common in many vertebrates, including primates. However, dispersal patterns in New World primates may vary among closely related taxa or populations in different local environments. Here, we test for SBD in an endangered New World primate, the Central American Squirrel Monkey (Saimiri oerstedii citrinellus). Previous studies of behavioral ecology suggest predominantly female dispersal in S.o. oerstedii in the Southern Pacific region of Costa Rica. However, our genetic data do not support strongly female-biased dispersal in S.o. citrinellus in the Central Pacific region. Our tests for SBD using microsatellite data including comparisons of isolation-by-distance, AI(c) , and F(ST) values between males and females were not significant. Also, we found greater population genetic structure in mitochondrial markers than in microsatellite markers, indicative of predominantly male dispersal. We conclude that both sexes disperse in S.o. citrinellus, and that males probably disperse over longer distances. We discuss how spatial and temporal variation among local populations should be taken into account when studying dispersal patterns and especially sex bias. PMID- 22038890 TI - Are biomechanical properties predictive of the success of prostheses used in stress urinary incontinence and pelvic organ prolapse? A systematic review. AB - AIMS: Progressive weakness in pelvic floor tissues is extremely common and leads to the distressing problems of stress urinary incontinence (SUI) and pelvic organ prolapse (POP). There has been extensive work on a vast array of materials spanning synthetics, autografts, allografts, and xenografts. Uniaxial testing of materials has been used to predict their success and rates of erosion. We aimed to compare the uniaxial properties of prostheses to native paravaginal tissue and correlate these to their success and erosion rates. METHODS: We performed a systematic review of the literature to identify the biomechanical properties of paravaginal tissue and of prostheses used in the treatment of SUI and POP. We examined to what extent these findings correlated to their reported success and erosion rates. RESULTS: Biomechanical properties have been determined for prostheses used in the treatment of POP and SUI both pre- and post-implantation in animal models. Implantation generally led to a decrease in ultimate tensile strength and Young's modulus. We were unable to find any simple correlation between the uniaxial mechanical properties of materials and their success or erosion rates. CONCLUSIONS: Mechanical properties of prostheses, as measured by uniaxial testing, only appears to form part of the picture. We suggest implant integration and host responses to materials, as well as the biomechanical properties of the materials need to be considered to design materials to achieve lasting clinical benefit. PMID- 22038891 TI - Severe acute hypertension among inpatients admitted from the emergency department. AB - BACKGROUND: Hospitalists often treat patients with severe acute hypertension (AH) presenting to the hospital. Little is known about the epidemiology of this syndrome. OBJECTIVE: To examine the prevalence of severe AH in patients admitted through the emergency department (ED) and its associated outcomes. DESIGN: A cohort study using retrospectively collected vital signs and other clinical data. PATIENTS: A total of 1,290,804 adults admitted between 2005 and 2007. SETTING: One hundred fourteen acute-care hospitals. MEASUREMENTS: Severe AH was defined as at least 1 systolic blood pressure (SBP) >180 mmHg. We used multivariable regression to estimate AH-attributable in-hospital mortality, need for mechanical ventilation (MV), and length of stay (LOS). RESULTS: Severe AH occurred in 178,131 (13.8%) patients. Disease categories with the highest prevalence were nervous (29.0%), circulatory (16.0%), endocrine (14.7%), and kidney/urinary (13.5%). The overall in-hospital mortality was 3.6%. The relationship between severe AH strata and mortality was graded for nervous system diseases; mortality rates for each 10 mmHg increase in SBP from 180 to >220 mmHg were 6.5%, 8.1%, 9.9%, 12.0%, and 19.7%, respectively (P < 0.0001). The relationship between severe AH strata and need for MV was graded in the most pronounced way in respiratory and circulatory conditions (P < 0.0001). The relationship between severe AH strata and LOS was graded in most disease categories (P < 0.0001). CONCLUSIONS: Severe AH appears common and its prevalence varies by underlying clinical condition. Severe AH is associated with excess in-hospital mortality for patients with nervous system diseases and, for most disease categories, prolongs hospitalization. PMID- 22038892 TI - Multifocal pyoderma gangrenosum resistant to infliximab in active ulcerative colitis: don't forget the role of cyclosporin. PMID- 22038893 TI - Molecular crystal lithography: a facile and low-cost approach to fabricate nanogap electrodes. AB - A novel cost-efficient and facile technique, molecular crystal lithography, to fabricate nanogap electrodes efficiently is reported. The gap width of the electrodes can be tuned from ~9 nm to several micrometers. Organic field-effect transistors based on the nanogap electrodes all exhibit a high performance, indicating the effectiveness and practicability of molecular crystal lithography for mass production of nanogap electrodes. PMID- 22038894 TI - A semi-empirical approach for predicting unobserved peptide MS/MS spectra from spectral libraries. AB - Spectral library searching is a promising alternative to sequence database searching in peptide identification from MS/MS spectra. The key advantage of spectral library searching is the utilization of more spectral features to improve score discrimination between good and bad matches, and hence sensitivity. However, the coverage of reference spectral library is limited by current experimental and computational methods. We developed a computational approach to expand the coverage of spectral libraries with semi-empirical spectra predicted from perturbing known spectra of similar sequences, such as those with single amino acid substitutions. We hypothesized that the peptide of similar sequences should produce similar fragmentation patterns, at least in most cases. Our results confirm our hypothesis and specify when this approach can be applied. In actual spectral searching of real data sets, the sensitivity advantage of spectral library searching over sequence database searching can be mostly retained even when all real spectra are replaced by semi-empirical ones. We demonstrated the applicability of this approach by detecting several known non synonymous single-nucleotide polymorphisms in three large human data sets by spectral searching. PMID- 22038895 TI - Epithelial-mesenchymal transition in breast cancer lines is mediated through PDGF D released by tissue-resident stem cells. AB - Epithelial-mesenchymal transition (EMT) generates tumor cells with stem cell properties. The aim of our study was to investigate the effects of adipose tissue derived stem cells (ASCs) on EMT of cancer cells and to further investigate the mechanisms involved. We demonstrate that conditioned medium from ASCs induces breast cancer cells (4T1) to express mesenchymal markers such as fibronectin, alpha smooth muscle actin and vimentin. Flow cytometry analyses show that ASC conditioned medium promotes the expansion of CD44high/CD24low cancer stem cells. Soft agar assays using T47D, BT474 and MCF-7 breast cancer cells reveals that ASC conditioned medium promotes the anchorage-independent growth of cancer cells. These effects were inhibited by a neutralizing antibody against platelet-derived growth factor-D (PDGF-D). Furthermore, PDGF-D treated breast cancer cells grow faster in a mouse model, and this effect could be neutralized by a PDGF antibody. In conclusion, our data show that tissue-resident stem cells interact with the cancer microenvironment via PDGF-D, induce EMT in the cancer cells in a paracrine fashion, thereby increasing the number of cancer stem cells and increase tumor growth in a PDGF dependent manner. Our findings shed new light on mechanisms where local tissue-resident stem cells are able to promote the growth of breast cancer cells. Possibly this could open up a novel selective therapeutic strategy targeting EMT pathways and the specific communication between tissue-resident normal stem cell and cancer stem cells, assuming that the blockage of PDGF-D pathways is critical for tumor growth but would not affect normal tissue homeostasis. PMID- 22038896 TI - Setting a new standard: updating the vaginal distention translational model for stress urinary incontinence. AB - AIMS: The vaginal distention (VD) translational model for postpartum stress urinary incontinence (SUI) is potentially biased for use in evaluating animals with increasing phenotypic size (obesity) due to a fixed VD volume. Our study had three principle and two secondary aims. First, to examine both ex vivo and in vivo catheter pressure changes during volume distention. Secondly, to determine mean pressure at current volume standard for use as target pressure (TP) for VD under isobaric (IB) conditions. Thirdly, to demonstrate feasibility and equivalence of VD at TP versus isovolumetric (IV) standard. Secondary aims were to demonstrate decreased variability (IB vs. IV) and to review the effect of weight. METHODS: Ten French modified Foley catheters were inflated sequentially to 3.0 ml while connected (both in vivo and ex vivo) to a pressure transducer. Mean result generated TP. Thirty Sprague-Dawley rats (280-300 g) were then randomized to one of three groups: IV, IB at TP, or sham VD. Student's t-test was used to compare groups' leak point pressures (LPP) and simple linear regression was used to evaluate the effect of weight as a continuous variable. RESULTS: Catheter pressure/volume responses were demonstrated. Calculated TP was 531 mm Hg. LPP under conditions of IB and IV were statistically equivalent and were statistically lower than Sham. Variability was not statistically different between IB and IV groups. When treated as a continuous variable, weight had no effect on LPP. CONCLUSIONS: VD injury based on TP is feasible and reproducible. Understanding catheter pressure dynamics is valuable for investigating alternative rat phenotypes. PMID- 22038897 TI - Catechols in caffeic acid phenethyl ester are essential for inhibition of TNF mediated IP-10 expression through NF-kappaB-dependent but HO-1- and p38 independent mechanisms in mouse intestinal epithelial cells. AB - SCOPE: Caffeic acid phenethyl ester (CAPE) is an active constituent of honeybee propolis inhibiting nuclear factor (NF)-kappaB. The aims of our study were to provide new data on the functional relevance and mechanisms underlying the role of CAPE in regulating inflammatory processes at the epithelial interface in the gut and to determine the structure/activity relationship of CAPE. METHODS AND RESULTS: CAPE significantly inhibited TNF-induced IP-10 expression in intestinal epithelial cells. Using various analogues, we demonstrated that substitution of catechol hydroxyl groups and addition of one extra hydroxyl group on ring B reversed the functional activity of CAPE to inhibit IP-10 production. The anti inflammatory potential of CAPE was confirmed in ileal tissue explants and embryonic fibroblasts derived from TNF(DeltaARE/+) mice. Interestingly, CAPE inhibited both TNF- and LPS-induced IP-10 production in a dose-dependent manner, independently of p38 MAPK, HO-1 and Nrf2 signaling pathways. We found that CAPE did not inhibit TNF-induced IkappaB phosphorylation/degradation or nuclear translocation of RelA/p65, but targeted downstream signaling events at the level of transcription factor recruitment to the gene promoter. CONCLUSION: This study reveals the structure-activity effects and anti-inflammatory potential of CAPE in the intestinal epithelium. PMID- 22038898 TI - Energetic salts based on dipicrylamine and its amino derivative. AB - Energetic salts based on dipicrylamine and its amino derivative were synthesized. All salts were fully characterized by multinuclear NMR spectroscopy ((1)H, (13)C), vibrational spectroscopy (IR), and elemental analysis. Ethylenediammonium di-DPA (DPA=dipicrylamine) and 1,3-diaminoguanidinium DPA were further confirmed by single-crystal X-ray diffraction. These salts exhibit reasonable physical properties, such as high densities (1.71-1.81 g cm(-3)), good thermal stabilities (T(d) =155-285 degrees C), and low solubilities in water. The impact sensitivity of 1-methyl-3,4,5-triamino-1,2,4-triazolium DPA is lower than that of 2,4,6 trinitrotoluene (TNT), and for some other energetic salts their impact sensitivities are comparable to that of TNT. Based on experimental densities and theoretical calculations carried out by using the Gaussian 03 suite of programs, all the salts have calculated detonation pressures (22.5-27.8 GPa) and velocities (7226-7917 m s(-1)) that exceed those of conventional TNT. The toxicities of these salts measured by luminescent bacteria toxicity tests are much lower than that of TNT, and two binary eutectic mixtures with melting points that fall between 70 and 100 degrees C were identified. PMID- 22038899 TI - Clinical utility of antihuman lambda chain-based enzyme-linked immunosorbent assay (ELISA) versus double antigen ELISA for the detection of anti-infliximab antibodies. AB - BACKGROUND: Anti-infliximab antibodies (ATIs) are associated with lower serum infliximab (IFX) trough levels and diminished clinical response. The current most prevalent method for detection of ATI is a double-antigen (DA) enzyme-linked immunosorbent assay (ELISA) utilizing IFX for ligand and detection antibody. Serum IFX interferes with ATI measurement in this method. An alternative ELISA using antihuman lambda chain (AHLC) antibody for ATI detection may be less amenable to this interference. The aim of our study was to compare the performance of AHLC-ATI versus DA-ATI for prediction of clinical response and evaluate the clinical significance of positive ATI in the presence of detectable IFX levels in IFX-treated inflammatory bowel disease (IBD) patients. METHODS: In all, 63 patients' sera were analyzed for IFX levels and antibody levels by AHLC and DA. The results were compared with the clinical response to IFX. Percentage of patients with IFX+ATI+ status among IFX-treated patients and the clinical outcome of IFX+ATI+ patients were assessed. RESULTS: ATIs were demonstrated in 22/63 (34.9%) and 18/63 (28.5%) sera of patients by AHLC and DA assay, respectively (P = 0.6). Detectable ATI and in IFX was detected in four patients (6.3%) by AHLC but not by DA assay. IFX+ATI+ status was documented in 8.7% of available sera and was associated with a trend for loss of response. CONCLUSIONS: AHLC and DA ELISA are equally effective for ATI detection in patients with undetectable serum IFX. AHLC ELISA detects ATI in some patients with detectable serum IFX. This IFX+ATI+ status may be a harbinger of evolving loss of response to the drug. PMID- 22038900 TI - Improved treatment outcomes with (18) F-FDG PET/CT for patients with advanced head and neck squamous cell carcinoma. AB - BACKGROUND: The aim of this study was to assess the impact of (18) F-fluoro-2 deoxy-D-glucose ((18) F-FDG) PET/CT on survival for patients with head and neck squamous cell carcinoma correlated with a matched patient cohort. METHODS: In all, disease in 58 patients was initially staged using (18) F-FDG PET/CT. A case control analysis was done with 63 patients who disease was staged without (18) F FDG-PET/CT. RESULTS: Disease-specific survival (DSS) and overall survival (OS) did not show significant differences between both groups. Statistical analysis revealed no difference in DSS and OS between the 2 groups for patients treated by radiochemotherapy (p = .975 and p = .671). In the analysis of survival in patients treated by a combined approach (surgery + radiochemotherapy), a significant difference in favor of patients evaluated by (18) F-FDG PET/CT was found (p = .05 and p = .027). CONCLUSIONS: Addition of (18) F-FDG PET/CT in patients treated by surgery and conformal radiochemotherapy improves outcome. This may be due to the more comprehensive topographic orientation of the primary tumor for the surgeon. PMID- 22038901 TI - Interpretation of nuclear resonant vibrational spectra of rubredoxin using a combined quantum mechanics and molecular mechanics approach. AB - Nuclear resonant vibrational spectra of the reduced and oxidized form of a mutant of rubredoxin from Pyrococcus abyssii were measured and are compared with simulated spectra that were calculated by a combined quantum mechanics (QM) and molecular mechanics (MM) method. Density functional theory was used for the QM level. Calculations were performed for different models of rubredoxin. Realistic spectra were simulated with reduced models that include at least the iron center, the four cysteins coordinating it, and the residues connected to the cysteins together with a QM layer that comprises the first two coordination shells of the iron center. Larger QM layers did not lead to significant changes of the simulated spectra. PMID- 22038902 TI - Inequity aversion in relation to effort and relationship quality in long-tailed Macaques (Macaca fascicularis). AB - Social animals may employ evolved implicit rules to maintain a balance between cooperation and competition. Inequity aversion (IA), the aversive reaction to an unequal distribution of resources, is considered such a rule to avoid exploitation between cooperating individuals. Recent studies have revealed the presence of IA in several nonhuman species. In addition, it has been shown that an effort is crucial for this behavior to occur in animals. Moreover, IA may well depend on the partner's identity. Although dominant individuals typically monopolize food, subordinate individuals obtain less preferred food and usually do not protest. Furthermore, "friends" may pay less attention to equity than "nonfriends." We tested whether long-tailed macaques show IA with different cost benefit ratios. In addition, we determined whether IA depends on relationship quality (RQ). Dominant subjects expressed IA only when a small effort was required. At a very large effort, however, long-tailed macaques did not show IA, possibly owing to bottom effects on the number of rewards they aim to receive. Moreover, and contrary to our predictions, an individual's inequity response was similar when tested with a "friend" or a "nonfriend." Therefore, we conclude that long-tailed macaques show IA only in conditions of moderate effort, yet that IA seems independent of RQ. Furthermore, IA may not be domain specific. Altogether, IA may be a trait present in all species that habitually cooperate, independent of their social organization. PMID- 22038903 TI - LRRK2 haplotype-sharing analysis in Parkinson's disease reveals a novel p.S1761R mutation. AB - BACKGROUND AND OBJECTIVE: Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene at chromosome 12q12 are the most common genetic cause of sporadic and familial late-onset Parkinson's disease. Our aim was to identify novel LRRK2 mutations in late-onset Parkinson's disease families. DESIGN: We analyzed chromosome 12p11.2-q13.1 haplotypes in 14 late-onset Parkinson's disease families without known LRRK2 mutations. RESULTS: Haplotype analysis identified 12 families in which the affected subjects shared chromosome 12p11.2-q13.1 haplotypes. LRRK2 sequencing revealed a novel co-segregating missense mutation in exon 36 (c.5281A>C; p.S1761R) located within a highly conserved region of the COR [C terminal of ROC (Ras of complex proteins)] domain wherein it could deregulate LRRK2 kinase activity by modifying ROC-COR dimer stability. p.S1761R was present in a late-onset Parkinson's disease family and in 2 unrelated Parkinson's disease subjects, but not in 2491 healthy controls. LRRK2 p.S1761R carriers developed levodopa-responsive asymmetrical parkinsonism, with variable age at onset (range: 37-72 years) suggesting age-dependent penetrance. These findings indicate that mutations interfering with LRRK2 ROC-COR domain dimerization lead to typical Parkinson's disease. PMID- 22038904 TI - Sensitive single-molecule protein quantification and protein complex detection in a microarray format. AB - Single-molecule protein analysis provides sensitive protein quantitation with a digital read-out and is promising for studying biological systems and detecting biomarkers clinically. However, current single-molecule platforms rely on the quantification of one protein at a time. Conventional antibody microarrays are scalable to detect many proteins simultaneously, but they rely on less sensitive and less quantitative quantification by the ensemble averaging of fluorescent molecules. Here, we demonstrate a single-molecule protein assay in a microarray format enabled by an ultra-low background surface and single-molecule imaging. The digital read-out provides a highly sensitive, low femtomolar limit of detection and four orders of magnitude of dynamic range through the use of hybrid digital-analog quantification. From crude cell lysate, we measured levels of p53 and MDM2 in parallel, proving the concept of a digital antibody microarray for use in proteomic profiling. We also applied the single-molecule microarray to detect the p53-MDM2 protein complex in cell lysate. Our study is promising for development and application of single-molecule protein methods because it represents a technological bridge between single-plex and highly multiplex studies. PMID- 22038905 TI - High-resolution analysis of alterations in medullary thyroid carcinoma genomes. AB - Hereditary and sporadic medullary thyroid carcinoma (MTC) are closely associated with RET proto-oncogene mutations. However, the role of additional changes in the tumor genomes remains unclear. Our objective was the identification of chromosomal regions involved in MTC tumorigenesis and to assess their significance by using MTC-derived cell lines. We used array-CGH (comparative genomic hybridization) to map chromosomal imbalances in 52 primary tumors and ten metastases. Eleven tumors (11/52, 21%) were hereditary and 41 (41/52, 79%) were sporadic. Among the latter, 15 tumors (15/41, 37%) harbored RET mutations. Furthermore, we characterized five MTC cell lines in detail and evaluated the tumorigenicity by severe combined immunodeficiency (SCID)-mouse experiments. Most MTCs had only few copy number changes, and losses of chromosomes 1p, 4q, 19p and 22q were observed most frequently. The number of chromosomal aberrations increased in metastases. Twenty-three percent (12/52) of the primary tumors did not even show any chromosomal gains and losses. We injected three cell lines (two of these were without chromosomal changes and pathogenic RET mutations) into immune deficient SCID mice, and in each case, we observed rapid tumor growth at the injection sites. Our data suggest that MTCs--in contrast to most other tumor entities--do not acquire a multitude of genomic imbalances. SCID mouse experiments performed with chromosomally normal cell lines and without RET mutations suggest that presently unknown submicroscopic genomic changes are sufficient in MTC tumorigenesis. PMID- 22038906 TI - Bilingualism tunes the anterior cingulate cortex for conflict monitoring. AB - Monitoring and controlling 2 language systems is fundamental to language use in bilinguals. Here, we reveal in a combined functional (event-related functional magnetic resonance imaging) and structural neuroimaging (voxel-based morphometry) study that dorsal anterior cingulate cortex (ACC), a structure tightly bound to domain-general executive control functions, is a common locus for language control and resolving nonverbal conflict. We also show an experience-dependent effect in the same region: Bilinguals use this structure more efficiently than monolinguals to monitor nonlinguistic cognitive conflicts. They adapted better to conflicting situations showing less ACC activity while outperforming monolinguals. Importantly, for bilinguals, brain activity in the ACC, as well as behavioral measures, also correlated positively with local gray matter volume. These results suggest that early learning and lifelong practice of 2 languages exert a strong impact upon human neocortical development. The bilingual brain adapts better to resolve cognitive conflicts in domain-general cognitive tasks. PMID- 22038907 TI - White matter network abnormalities are associated with cognitive decline in chronic epilepsy. AB - Patients with chronic epilepsy frequently display cognitive comorbidity and might have widespread network abnormalities outside the epileptic zone, which might affect a variety of cognitive functions and global intelligence. We aimed to study the role of white matter connectivity in cognitive comorbidity. Thirty-nine patients with nonsymptomatic localization-related epilepsy and varying degrees of cognitive impairment and 23 age-matched healthy controls were included. Whole brain white matter networks were constructed from fiber tractography. Weighted graph theoretical analysis was performed to study white matter network abnormalities associated with epilepsy and cognition. Patients with severe cognitive impairment showed lower clustering (a measure of brain network segregation) and higher path length (a measure of brain network integration) compared with the healthy controls and patients with little or no cognitive impairment, whereas whole brain white matter volume did not differ. Correlation analyses revealed that IQ and cognitive impairment were strongly associated with clustering and path lengths. This study revealed impaired white matter connectivity, associated with cognitive comorbidity in patients with chronic epilepsy. As whole brain white matter volumes were preserved in the patient group, our results suggest an important role for the network topology rather than volumetric changes, in epilepsy with cognitive decline. PMID- 22038908 TI - CSF biomarker and PIB-PET-derived beta-amyloid signature predicts metabolic, gray matter, and cognitive changes in nondemented subjects. AB - Beta-amyloid (Abeta) is a histopathological hallmark of Alzheimer's disease dementia, but high levels of Abeta in the brain can also be found in a substantial proportion of nondemented subjects. Here we investigated which 2-year rate of brain and cognitive changes are present in nondemented subjects with high and low Abeta levels, as assessed with cerebrospinal fluid and molecular positron emission tomography (PET)-based biomarkers of Abeta. In subjects with mild cognitive impairment, increased brain Abeta levels were associated with significantly faster cognitive decline, progression of gray matter atrophy within temporal and parietal brain regions, and a trend for a faster decline in parietal Fludeoxyglucose (FDG)-PET metabolism. Changes in gray matter and FDG-PET mediated the association between Abeta and cognitive decline. In contrast, elderly cognitively healthy controls (HC) with high Abeta levels showed only a faster medial temporal lobe and precuneus volume decline compared with HC with low Abeta. In conclusion, the current results suggest not only that both functional and volumetric brain changes are associated with high Abeta years before the onset of dementia but also that HC with substantial Abeta levels show higher Abeta pathology resistance, lack other pathologies that condition neurotoxic effects of Abeta, or accumulated Abeta for a shorter time period. PMID- 22038909 TI - Adaptive intrinsic plasticity in human dentate gyrus granule cells during temporal lobe epilepsy. AB - Granule cells in the dentate gyrus are only sparsely active in vivo and survive hippocampal sclerosis (HS) during temporal lobe epilepsy better than neighboring cells. This phenomenon could be related to intrinsic properties specifically adapted to counteract excitation. We studied the mechanisms underlying the excitability of human granule cells using acute hippocampal slices obtained during epilepsy surgery. Patch-clamp recordings were combined with pharmacology, immunocytochemistry, and computer simulations. The input resistance of granule cells correlated negatively with the duration of epilepsy and the degree of HS. Hyperpolarization-activated, ZD7288-sensitive cation (I(H), HCN) currents and highly Ba(2+)-sensitive, inwardly rectifying K(+) (Kir) currents (and HCN1 and Kir2.2 protein) were present somatodendritically and further enhanced in patients with severe HS versus mild HS. The properties and function of I(H) were characterized in granule cells. Although I(H) depolarized the membrane, it strongly reduced the input resistance and shifted the current-frequency function to higher input values. The shunting influence of HCN and Kir was similar and these conductances correlated. Resonance was not observed. Simulations suggest that the combined upregulation of Kir and HCN conductances attenuates excitatory synaptic input, while stabilizing the membrane potential and responsiveness. Thus, granule cells homeostatically downscale their input-output transfer function during epilepsy. PMID- 22038910 TI - Dopamine D1/D5 receptors contribute to de novo hippocampal LTD mediated by novel spatial exploration or locus coeruleus activity. AB - The neurons of the locus coeruleus (LC) fire in response to novelty, and LC activation coupled with hippocampal afferent stimulation leads to long-term depression (LTD). The encoding of novel spatial information also involves activation of dopamine D1/D5 receptors. It is unclear if, or how, the noradrenergic and dopaminergic systems interact mechanistically in processing novelty. Novel spatial exploration when coupled with Schaffer collateral (SC) test-pulse stimulation results in short-term depression at SC-CA1 synapses, which is not observed in the absence of afferent stimulation. However, activation of D1/D5 receptors under these conditions without concomitant afferent stimulation enables slow-onset depression. LTD (>24 h) is facilitated when novel exploration occurs concurrently with low-frequency stimulation of CA1. Effects are not improved by a D1/D5 agonist. Facilitation of LTD (>4 h) by coupling LC stimulation with CA1 test-pulse stimulation was blocked by a D1/D5 antagonist, however, as was habituation to the holeboard environment. Novel spatial learning during LC stimulation did not enhance LTD further, whereas D1/D5 agonist treatment enabled LTD to persist for over 24 h. These data suggest that the regulation of hippocampal LTD by the LC is supported by D1/D5 receptors and that their contribution to information storage becomes important when the thresholds for persistent LTD have not been reached. PMID- 22038911 TI - Effect of esophagus distention on urinary bladder function in rats. AB - AIMS: Micturition process is a spinobulbospinal reflex that is affected by the viscero-visceral interactions due to convergent inputs into spinal and/or supraspinal centers controlling that reflex. Although interaction between bladder and other pelvic organs, such as colon, are well studied, the viscero-visceral interaction between urinary bladder and internal organs in other regions are rarely studied. METHODS: In the present study, continuous filling cystometry recordings, in male rats, were used to investigate the effects of mechanical stimulation of distal-esophagus (distention), as well as, electrical stimulation of abdominal branches of the vagus nerve on urinary bladder micturition cycles. RESULTS: Distal esophagus distention and electrical stimulation of the vagus nerve significantly increased the micturition frequency through decreasing the time of the storage phase of the micturition cycle. However, bilateral cervical vagotomy eliminated the effects of distal esophagus distention and electrical stimulation of vagus nerve on micturition cycles. CONCLUSIONS: The results of this study indicate that there is a viscero-visceral interaction between esophagus and urinary bladder, which is mediated through vagal afferents. Understanding the properties of the viscero-visceral interactions affecting the urinary bladder will help in the diagnosis and management of micturition problems. PMID- 22038912 TI - Innate immune responses and modified extracellular matrix regulation characterize bacterial infection and cellular/connective tissue changes in scarring trachoma. AB - Trachoma is the most common infectious cause of blindness and a major public health problem in many developing countries. It is caused by recurrent ocular infection with Chlamydia trachomatis in childhood, with conjunctival scarring seen later in life. The pathogenesis of trachomatous scarring, however, is poorly understood, and this study was carried out to investigate the immunofibrogenic correlates of trachomatous conjunctival scarring. A case-control study of 363 cases with conjunctival scarring and 363 control participants was conducted. Investigations included in vivo confocal microscopy (IVCM) assessment, quantitative real-time PCR gene expression, C. trachomatis detection, and nonchlamydial bacterial culture. Trachomatous scarring was found to be strongly associated with a proinflammatory, innate immune response with increased expression of psoriasin, interleukin-1beta, tumor necrosis factor alpha, defensin beta4A, chemokine ligand 5, and serum amyloid A1. There was also differential expression of various modifiers of the extracellular matrix, including metalloproteinases 7, 9, 10, and 12, tissue inhibitor of matrix metalloproteinase 1, and secreted protein acidic cystein-rich-like 1. The expression of many of these genes was also significantly associated with the presence of nonchlamydial bacterial infection. These infections had a marked effect on conjunctival immune processes, including an increased inflammatory infiltrate and edema seen with IVCM. This study supports the possibility that the immunofibrogenic response in scarring trachoma is partly stimulated by nonchlamydial bacterial infection, which is characterized by the expression of innate factors. PMID- 22038913 TI - LipC (Rv0220) is an immunogenic cell surface esterase of Mycobacterium tuberculosis. AB - We have reported previously the identification of novel proteins of Mycobacterium tuberculosis by the immunoscreening of an expression library of M. tuberculosis genomic DNA with sera obtained from M. tuberculosis-infected rabbits at 5 weeks postinfection. In this study, we report the further characterization of one of these antigens, LipC (Rv0220). LipC is annotated as a member of the Lip family based on the presence of the consensus motif "GXSXG" characteristic of esterases. Although predicted to be a cytoplasmic enzyme, we provide evidence that LipC is a cell surface protein that is present in both the cell wall and the capsule of M. tuberculosis. Consistent with this localization, LipC elicits strong humoral immune responses in both HIV-negative (HIV-) and HIV-positive (HIV+) tuberculosis (TB) patients. The absence of anti-LipC antibodies in sera from purified protein derivative-positive (PPD+) healthy subjects confirms its expression only during active M. tuberculosis infection. Epitope mapping of LipC identified 6 immunodominant epitopes, 5 of which map to the exposed surface of the modeled LipC protein. The recombinant LipC (rLipC) protein also elicits proinflammatory cytokine and chemokine responses from macrophages and pulmonary epithelial cells. rLipC can hydrolyze short-chain esters with the carbon chain containing 2 to 10 carbon atoms. Together, these studies demonstrate that LipC is a novel cell surface-associated esterase of M. tuberculosis that is highly immunogenic and elicits both antibodies and cytokines/chemokines. PMID- 22038914 TI - The intact dupA cluster is a more reliable Helicobacter pylori virulence marker than dupA alone. AB - The duodenal ulcer promoting (dupA) gene, located in the plasticity region of Helicobacter pylori, is associated with duodenal ulcer development. dupA was predicted to form a type IV secretory system (T4SS) with vir genes around dupA (dupA cluster). We investigated the prevalence of dupA and dupA clusters and clarified associations between the dupA cluster status and clinical outcomes in the U.S. population. In all, 245 H. pylori strains were examined using PCR to evaluate the status of dupA and the adjacent vir genes predicted to form T4SS, in addition to the status of cag pathogenicity island (PAI). The associations between dupA cluster status and interleukin-8 (IL-8) and IL-12 production were also examined. The presence of dupA and all adjacent vir genes were defined as a complete dupA cluster. Many variations related to the status of dupA and dupA cluster genes were identified. Concurrent H. pylori infection and the presence of a complete dupA cluster increases duodenal ulcer risk compared to H. pylori infection with incomplete dupA cluster or without the dupA gene independent on the cag PAI status (adjusted odds ratio, 2.13; 95% confidence interval, 1.13 to 4.03). Gastric mucosal IL-8 levels were also significantly higher in the complete dupA cluster group than in other groups (P=0.01). In conclusion, although the causal relationship between the dupA cluster and duodenal ulcer development is not proved, the presence of a complete dupA cluster but not dupA alone, is associated with duodenal ulcer development. PMID- 22038915 TI - PPE38 modulates the innate immune response and is required for Mycobacterium marinum virulence. AB - The proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) family proteins are prevalent in pathogenic mycobacteria and play a diverse role in mycobacterial pathogenesis. While some members have been studied, the function of most PE/PPE proteins remains unknown. In this study, we isolated a transposon inactivated PPE38 mutant of Mycobacterium marinum and characterized its phenotype. We found that the PPE38 protein is associated with the cell wall and exposed on the cell surface. The inactivation of PPE38 altered the bacterial cell surface properties and led to deficiencies in cord formation, sliding motility, and biofilm formation. The PPE38 mutant was defective in phagocytosis by macrophages and exhibited reduced virulence in adult zebrafish. We also found that PPE38 is involved in the induction of proinflammatory cytokines in infected macrophages. Together, our results indicate that PPE38, a previously uncharacterized protein, plays a role in mycobacterial virulence, presumably by modulating the host innate immune response. PMID- 22038916 TI - Dectin-1-dependent interleukin-22 contributes to early innate lung defense against Aspergillus fumigatus. AB - We have previously reported that mice deficient in the beta-glucan receptor Dectin-1 displayed increased susceptibility to Aspergillus fumigatus lung infection in the presence of lower interleukin 23 (IL-23) and IL-17A production in the lungs and have reported a role for IL-17A in lung defense. As IL-23 is also thought to control the production of IL-22, we examined the role of Dectin-1 in IL-22 production, as well as the role of IL-22 in innate host defense against A. fumigatus. Here, we show that Dectin-1-deficient mice demonstrated significantly reduced levels of IL-22 in the lungs early after A. fumigatus challenge. Culturing cells from enzymatic lung digests ex vivo further demonstrated Dectin-1-dependent IL-22 production. IL-22 production was additionally found to be independent of IL-1beta, IL-6, or IL-18 but required IL 23. The addition of recombinant IL-23 augmented IL-22 production in wild-type (WT) lung cells and rescued IL-22 production by lung cells from Dectin-1 deficient mice. In vivo neutralization of IL-22 in the lungs of WT mice resulted in impaired A. fumigatus lung clearance. Moreover, mice deficient in IL-22 also demonstrated a higher lung fungal burden after A. fumigatus challenge in the presence of impaired IL-1alpha, tumor necrosis factor alpha (TNF-alpha), CCL3/MIP 1alpha, and CCL4/MIP-1beta production and lower neutrophil recruitment, yet intact IL-17A production. We further show that lung lavage fluid collected from both A. fumigatus-challenged Dectin-1-deficient and IL-22-deficient mice had compromised anti-fungal activity against A. fumigatus in vitro. Although lipocalin 2 production was observed to be Dectin-1 and IL-22 dependent, lipocalin 2-deficient mice did not demonstrate impaired A. fumigatus clearance. Moreover, lung S100a8, S100a9, and Reg3g mRNA expression was not lower in either Dectin-1 deficient or IL-22-deficient mice. Collectively, our results indicate that early innate lung defense against A. fumigatus is mediated by Dectin-1-dependent IL-22 production. PMID- 22038917 TI - Association and evidence for linked recognition of type IV secretion system proteins VirB9-1, VirB9-2, and VirB10 in Anaplasma marginale. AB - Like several other bacterial pathogens, Anaplasma marginale has an outer membrane that induces complete protection from infection and disease. However, the proteins that confer protective immunity and whether protection requires interacting proteins and/or linked T-cell and immunoglobulin G epitopes are not known. Our goal is to target the conserved type IV secretion system (T4SS) to identify conserved, immunogenic membrane proteins that are interacting and linked recognition candidates. Linked recognition is a process by which a B cell is optimally activated by a helper T cell that responds to the same, or physically associated, antigen. A. marginale T4SS proteins VirB2, VirB4-1, VirB4-2, VirB6-1, VirB7, VirB8-2, VirB9-1, VirB9-2, VirB10, VirB11, and VirD4 were screened for their ability to induce IgG and to stimulate CD4+ T cells from outer membrane vaccinated cattle. VirB9-1, VirB9-2, and VirB10 induced the strongest IgG and T cell responses in the majority of cattle, although three animals with major histocompatibility complex class II DRB3 restriction fragment length polymorphism types 8/23, 3/16, and 16/27 lacked T-cell responses to VirB9-1, VirB9-1 and VirB9 2, or VirB9-2 and VirB10, respectively. For these animals, VirB9-1-, VirB9-2-, and VirB10-specific IgG production may be associated with T-cell help provided by responses to an interacting protein partner(s). Interacting protein partners indicated by far-Western blotting were confirmed by immunoprecipitation assays and revealed, for the first time, specific interactions of VirB9-1 with VirB9-2 and VirB10. The immunogenicity and interactions of VirB9-1, VirB9-2, and VirB10 justify their testing as a linked protein vaccine against A. marginale. PMID- 22038918 TI - Interleukin-4 (IL-4) and IL-13 suppress excessive neutrophil infiltration and hepatocyte damage during acute murine schistosomiasis japonica. AB - Due to the importance of neutrophils and proinflammatory cytokines in schistosomal liver damage, we analyzed the mechanisms underlying neutrophil and proinflammatory responses in murine schistosomiasis japonica. We found that granulomatous inflammation around parasite eggs in the liver was greater in Schistosoma japonicum-infected IL-4-/- IL-13-/- (double-knockout [DKO]) mice than in infected wild-type (WT) mice at 6 weeks, but not at 8 weeks, postinfection, suggesting the importance of Th2 responses in these typical hepatic lesions. Infected DKO mice also showed increased neutrophil infiltration accompanying more severe pathology, as shown by the enhanced necrosis of hepatocytes. This was not likely due to a Th1/Th2 imbalance, because there was no detectable increase in gamma interferon (IFN-gamma) production in these DKO mice. mRNA expression of interleukin-17A (IL-17A), proinflammatory cytokines, and the neutrophil chemoattractant CXCL2 in liver was higher in infected DKO mice than in WT mice. However, in IL-4-/- IL-13-/- IL-17A-/- (triple-knockout [TKO]) mice, the absence of IL-17A was associated with only marginal differences in schistosomal liver damage, suggesting that IL-17A is only partially responsible for neutrophil driven hepatic damage. Furthermore, the expression of mRNAs encoding proinflammatory cytokines was not under the control of IL-17A in TKO mice. These findings indicate that IL-4 and IL-13 suppress excessive neutrophil recruitment, proinflammatory cytokine production, and hepatic damage during the acute stage of S. japonicum infection, suggesting that neutrophils and proinflammatory cytokines are mainly responsible for hepatocyte damage during acute murine schistosomiasis japonica. However, neutrophil induction and the production of proinflammatory cytokines were not due solely to IL-17A. PMID- 22038919 TI - Crocin promotes non-rapid eye movement sleep in mice. AB - Crocus sativus L. (saffron) has been traditionally used for the treatment of insomnia and other diseases of the nervous systems. Two carotenoid pigments, crocin and crocetin, are the major components responsible for the various pharmacological activities of C. sativus L. In this study, we examined the sleep promoting activity of crocin and crocetin by monitoring the locomotor activity and electroencephalogram after administration of these components to mice. Crocin (30 and 100 mg/kg) increased the total time of non-rapid eye movement (non-REM) sleep by 60 and 170%, respectively, during a 4-h period from 20:00 to 24:00 after its intraperitoneal administration at a lights-off time of 20:00. Crocetin (100 mg/kg) also increased the total time of non-REM sleep by 50% after the administration. These compounds did not change the amount of REM sleep or show any adverse effects, such as rebound insomnia, after the induction of sleep. PMID- 22038920 TI - A subset of cutaneous and soft tissue mixed tumors are genetically linked to their salivary gland counterpart. AB - Neoplasms morphologically similar to mixed tumors and myoepitheliomas of the salivary glands, under the broad concept of myoepithelial neoplasia, have recently been defined in the skin and soft tissue; however, to date, no data have supported a shared genetic background with their salivary gland counterpart. From a large body of research, it has been well established that rearrangement of pleomorphic adenoma gene 1 (PLAG1) leads to aberrant expression of its protein and is pathogenically relevant in the development of salivary mixed tumors. On the other hand, in soft tissue lesions, compelling evidence suggests that EWSR1 is involved in a significant subset. To examine the hypothesis that there is a genetic link between these histologically similar tumors at different sites, we randomly selected 20 benign myoepitheliomas/mixed tumors of skin and soft tissue (10 cases each). Nineteen cases could be immunostained for PLAG1, of which 11 cases showed distinct nuclear staining with moderate or strong intensity in a significant number of cells. Interphase fluorescence in situ hybridization for PLAG1 was successfully performed in 11 cases (seven in skin and four in soft tissue) and was positive for gene rearrangement in eight cases (five in skin and three in soft tissue). All PLAG1-rearranged tumors, except one, had clear-cut ductal structures and were immunoreactive for PLAG1. In our series, tumors with PLAG1 alteration shared a common morphologic phenotype characterized by prominent tubuloductal differentiation, suggesting that myoepithelial neoplasms with genuine salivary gland-like morphology, so-called soft tissue/cutaneous mixed tumors, are genetically related to their salivary gland counterpart. PMID- 22038921 TI - Serum levels of N-acetylaspartate in Huntington's disease: preliminary results. PMID- 22038922 TI - Regulation by lipocalin-2 of neuronal cell death, migration, and morphology. AB - A secreted protein, lipocalin-2 (LCN2), has been previously shown to regulate a variety of cellular phenotypes such as cell death, migration, and morphology. The role of LCN2, however, appears to be different depending on the cellular context. Here, we investigated how LCN2 influences neuronal phenotypes by using primary cortical neuronal cell cultures and neuroblastoma cell lines as a model. When exposed to LCN2 protein, neurons and neuroblastoma cells were sensitized to cell death evoked by nitric oxide, oxidative stress, and tumor necrosis factor-alpha (TNF-alpha). A forced expression of lcn2 in glia enhanced neuronal cell death in cocultures of glia and neurons, indicating that both exogenous protein addition and endogenous expression of lcn2 give rise to similar results. Iron and BCL2 interacting mediator of cell death (BIM) protein were involved in LCN2-induced cell death sensitization, based on the studies using iron donor, chelator, siderophore, and short hairpin RNA (shRNA)-mediated knockdown of bim expression. Furthermore, cell migration assay and immunofluorescence microscopic observation revealed that LCN2 accelerated neuronal motility and process extension, suggesting multiple roles for LCN2 in the regulation of neuronal cell death, migration, and morphology. PMID- 22038925 TI - An optical olfactory sensor based on porous silicon infiltrated with room temperature ionic liquid arrays. PMID- 22038924 TI - Chemokines: established and novel targets in atherosclerosis. AB - In their role as small chemotactic cytokines, chemokines are crucial mediators and regulators of leukocyte trafficking during immune surveillance and inflammation. Their involvement in the development and progression of inflammatory diseases has been subject of intense investigation. Concordantly, the chemokine system has been explored in search for therapeutic targets to prevent or treat inflammatory disorders, such as atherosclerosis. Targeting the chemokine system offers various entry points for a causative treatment of this widespread and chronic illness. Although this approach has encountered some setbacks, several innovative compounds are currently in an advanced stage of development. In this review, the current standing of this dynamic field is highlighted and the potential advantages and drawbacks of particular strategies are discussed. PMID- 22038926 TI - Acute and chronic toxicity of chromium and cadmium to the tropical cladoceran pseudosida ramosa and the implications for ecotoxicological studies. AB - In this study, the acute and chronic toxicity of the metals chromium and cadmium were tested against the tropical freshwater cladoceran Pseudosida ramosa. Acute tests showed that the 48-h LC50 of chromium was 29 MUg L(-1) , while that of cadmium was 12 MUg L(-1) . P. ramosa had a similar sensitivity to those of other cladoceran species cultured in the same conditions as in this study, or a higher sensitivity when water hardness was raised. Long-term chronic exposure of P. ramosa to chromium decreased maternal survival, fecundity, and fertility at a concentration of 10 MUg L(-1) . For cadmium, reductions in the same endpoints were observed at a concentration of 3 MUg L(-1) . Moreover, the degree of toxicity of the chromium and cadmium to P. ramosa after release of the first brood was similar to the result obtained after 21 days, using reproduction as the endpoint. Brazilian water bodies located near industrial areas already show concentrations of chromium and cadmium higher than levels causing acute and chronic toxicity to P. ramosa in our study. Many water quality criteria in tropical regions are based on ecotoxicological tests with non-native species and, consequently, this may lead to errors of interpretation when the permitted maximum levels of for each toxic substance are established. Therefore, we reinforce the idea of using native species to establish the maximum concentrations of toxic substances in water quality criteria, especially for metals, since their effects are related to water hardness, pH, and temperature specific to each region. PMID- 22038927 TI - Tumor TP53 expression status, body mass index and prognosis in colorectal cancer. AB - Inactivation of the TP53 (p53) pathway by TP53 mutations is one of key steps in colorectal carcinogenesis. TP53 also plays an important role in cellular energy metabolism. We hypothesized that TP53-altered tumor cells might behave aggressively independent of energy balance, while progression of TP53-intact cells might depend on excess energy balance. Utilizing a database of 1,060 colon and rectal cancer patients in two prospective cohort studies, we evaluated TP53 expression by immunohistochemistry. Among 1,060 colorectal cancers, 457 (43%) tumors were positive for TP53. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical and tumoral features, including microsatellite instability, the CpG island methylator phenotype, LINE-1 methylation, KRAS, BRAF and PIK3CA. TP53 positivity was not significantly associated with cancer-specific survival in univariate analysis with HR of 1.16 [95% confidence interval (CI)=0.92-1.45], which became significant after stage adjustment (multivariate HR=1.30; 95% CI=1.02-1.65). Notably, we found a possible modifying effect of patient's body mass index (BMI) on tumor TP53. In non-obese patients (BMI<30 kg/m2), TP53 positivity was associated with shorter cancer specific survival (multivariate HR=1.53; 95% CI=1.17-2.00), while TP53 positivity was not significantly associated with survival among obese patients (BMI>=30 kg/m2). Effect of TP53 positivity on cancer-specific survival significantly differed by BMI (pinteraction=0.0051). The adverse effect of obesity on patient mortality was limited to TP53-negative patients. These molecular pathological epidemiology data may support a dual role of TP53 alterations in cell-cycle deregulation and cell autonomy with respect to energy balance status. PMID- 22038928 TI - Expression of genes encoding smooth muscle contractile proteins in vaginal tissue of women with and without pelvic organ prolapse. AB - AIMS: We hypothesize that the expression of genes encoding vaginal smooth muscle (SM) contractile proteins is altered in patients with pelvic organ prolapse (POP) and is influenced by age and menopausal status. We aim to analyze the expression of SM-myosin heavy chain (MHY11), caldesmon (CALD1), SM gamma-actin (ACTG2), and tropomyosin (TPM1), in premenopausal and postmenopausal women with advanced POP and asymptomatic controls. METHODS: During total hysterectomy we collected anterior vaginal wall biopsy samples from 55 women, 37 premenopausal (23 patients and 14 controls), and 18 postmenopausal women (13 patients and 5 controls). Total mRNA from the tissues was quantified by real-time RT-PCR. RESULTS: MHY11 gene expression was down-regulated in premenopausal POP patients compared to premenopausal controls (fivefold, P = 0.002). In the postmenopausal groups, we observed a sixfold increase in the CALD1 gene expression in POP patients compared to asymptomatic controls (P = 0.03). The gene expression of CALD1, ACTG2, and TPM1 was significantly down-regulated in vaginal tissue of healthy women after menopause (P < 0.05). CONCLUSION: Dysregulation of the vaginal SM content in POP patients involves alteration of different cellular pathways according to age and menopausal status. PMID- 22038929 TI - Compound CVT-E002 attenuates allergen-induced airway inflammation and airway hyperresponsiveness, in vivo. AB - Immune modulation has been a sought after means of therapy for atopic diseases. CVT-E002 is an extract derived from North American Ginseng shown to promote T helper-1-like responses. We determined what effect CVT-E002 could have in a mouse model of atopic asthma. We report that oral CVT-E002 inhibited the development of allergic airway inflammation and airway hyperresponsiveness. This correlated with an increased presence of interferon-gamma in the lung, and also increased regulatory T cells and IL-10. The ability of CVT-E002 to induce regulatory T-cell development was also seen in human in vitro co-cultures. PMID- 22038930 TI - Rapidly progressing diffuse Lewy body disease. PMID- 22038931 TI - Human bocavirus-the first 5 years. AB - Four species of human bocavirus (HBoV) have been recently discovered and classified in the Bocavirus genus (family Parvoviridae, subfamily Parvovirinae). Although detected both in respiratory and stool samples worldwide, HBoV1 is predominantly a respiratory pathogen, whereas HBoV2, HBoV3, and HBoV4 have been found mainly in stool. A variety of signs and symptoms have been described in patients with HBoV infection including rhinitis, pharyngitis, cough, dyspnea, wheezing, pneumonia, acute otitis media, fever, nausea, vomiting, and diarrhea. Many of these potential manifestations have not been systematically explored, and they have been questioned because of high HBoV co-infection rates in symptomatic subjects and high HBoV detection rates in asymptomatic subjects. However, evidence is mounting to show that HBoV1 is an important cause of lower respiratory tract illness. The best currently available diagnostic approaches are quantitative PCR and serology. This concise review summarizes the current clinical knowledge on HBoV species. PMID- 22038932 TI - Benzothiophene carboxamide derivatives as novel antimalarials. AB - Bromo-benzothiophene carboxamide derivatives have been shown in the preceding article to inhibit Plasmodium falciparum Enoyl-ACP reductase. Here, we report bromo-benzothiophene carboxamide derivatives as potent inhibitors of Plasmodium asexual blood-stages in vitro as well as in vivo in the mouse model. These compounds specifically impair the development of metabolically active trophozoite stage of intraerythrocytic cycle and the intravenous administration of 3-bromo-N (4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide (compound 6) enhances the longevity of P. berghei infected mice by 2 weeks compared to disease control animals thereby preventing the onset of ataxia and convulsions in treated mice. These compounds thus hold promise for the development of potent antimalarials. PMID- 22038935 TI - Curaxins: a new family of non-genotoxic multitargeted anticancer agents. PMID- 22038936 TI - Structures and stabilities of group 13 adducts [(NHC)(EX3)] and [(NHC)2(E2X(n))] (E=B to In; X=H, Cl; n=4, 2, 0; NHC=N-heterocyclic carbene) and the search for hydrogen storage systems: a theoretical study. AB - Quantum chemical calculations using density functional theory at the BP86/TZVPP level and ab initio calculations at the SCS-MP2/TZVPP level have been carried out for the group 13 complexes [(NHC)(EX(3))] and [(NHC)(2)(E(2)X(n))] (E=B to In; X=H, Cl; n=4, 2, 0; NHC=N-heterocyclic carbene). The monodentate Lewis acids EX(3) and the bidentate Lewis acids E(2) X(n) bind N-heterocyclic carbenes rather strongly in donor-acceptor complexes [(NHC)(EX(3))] and [(NHC)(2)(E(2)X(n))]. The equilibrium structures of the bidentate complexes depend on the electronic reference state of E(2)X(n), which may vary for different atoms E and X. All complexes [(NHC)(2)(E(2)X(4))] possess C(s) symmetry in which the NHC ligands bind in a trans conformation to the group 13 atoms E. The complexes [(NHC)(2)(E(2)H(2))] with E=B, Al, Ga have also C(s) symmetry with a trans arrangement of the NHC ligands and a planar CE(H)E(H)C moiety that has a E=E pi bond. In contrast, the indium complex [(NHC)(2)(In(2) H(2))] has C(i) symmetry with pyramidal-coordinated In atoms in which the hydrogen atoms are twisted above and below the CInInC plane. The latter C(i) form is calculated for all chloride systems [(NHC)(2)(E(2)Cl(2))], but the boron complex [(NHC)(2)(B(2)Cl(2))] deviates only slightly from C(s) symmetry. The B(2) fragment in the linear coordinated complex [(NHC)(2)(B(2))] has a highly excited (3)(1)Sigma(g)(-) reference state, which gives an effective B=B triple bond with a very short interatomic distance. The heavier homologues [(NHC)(2)(E(2))] (E=Al to In) exhibit a anti-periplanar arrangement of the NHC ligands in which the E(2) fragments have a (1)(1) Delta(g) reference state and an E=E double bond. The calculated energies suggest that the dihydrogen release from the complexes [(NHC)(EH(3))] and [(NHC)(2)(E(2)H(n))] becomes energetically more favourable when atom E becomes heavier. The indium complexes should therefore be the best candidates of the investigated series for hydrogen-storage systems that could potentially deliver dihydrogen at close to ambient temperature. The hydrogenation reaction of the dimeric magnesium(I) compound [LMgMgL] (L=beta-diketiminate) with [(NHC)(EH(3))] becomes increasingly exothermic with the trend BA found in Wiskott-Aldrich syndrome and X-linked thrombocytopenia in a Korean family. AB - Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) are caused by a mutation in the WAS gene on Xp11.22. We report two patients with IVS6+5G>A of WAS in a Korean family. The proband presented with classic WAS, whereas his maternal cousin had symptoms limited to XLT. Their mothers were proved to be carriers. The IVS6+5G>A mutation was reported to result in incomplete splicing of the donor site and typically associated with mild form of disease, XLT. Our observation of the intrafamilial variability of clinical manifestations of WAS further expands the genotype-phenotype correlations and suggests the presence of modifying genetic factors. PMID- 22038942 TI - 5,10-A2B2-type meso-substituted porphyrins--a unique class of porphyrins with a realigned dipole moment. AB - Current applications in porphyrin chemistry require the use of unsymmetrically substituted porphyrins. Many current industrial interests in optics and biomedicine require systems with either push-pull (electron-donating and withdrawing groups) or amphiphilic systems (hydrophobic and hydrophilic groups). In this context we present the class of 5,10-A(2)B(2)-type porphyrins for which two different substituents are positioned in diagonally opposite meso positions. Thus, the intramolecular dipole moment in these tetrapyrroles is positioned along a beta-beta vector passing through two pyrrole rings. This is opposite to the situation of the frequently used 5,15-A(2)BC porphyrins for which the dipole moment is oriented along a meso-meso axis. We have elaborated syntheses of the 5,10-A(2)B(2) porphyrins by using transition-metal-catalyzed transformations of 5,10-A(2) porphyrins or direct substitutions reactions thereof; this gives the target molecules in 22-77% overall yields. The compounds exhibit interesting structural, spectroscopic, and optical features and can serve as building blocks for new porphyrin arrays and applications. PMID- 22038943 TI - Genetic variation in odorant receptors contributes to variation in olfactory behavior in a natural population of Drosophila melanogaster. AB - Chemoreception is a principle modality by which organisms gain information from their environment, and extensive variation in odor-mediated behavior has been documented within and among species. To examine the mechanisms by which sensory systems mediate these responses, we ask to what extent variation in Drosophila melanogaster odorant receptor genes contributes to variation in odor-mediated behavior. Significant differences in behavioral responses to structurally similar odorants, methyl hexanoate and ethyl hexanoate, were found in a natural population. Polymorphisms in 3 genomic regions (Or22a/Or22b, Or35a, and Or47a) were identified and associated with variation in behavior to these esters. Overall similarity in association profiles for both odorants was observed, except for Or47a in which polymorphisms were associated solely with variation in responses to ethyl hexanoate. Our analyses were then extended to examine polymorphisms in 3 odorant receptors previously reported to contribute to variation in olfactory behavior for the chemically distinct odorants benzaldehyde and acetophenone. Two Or10a polymorphisms were associated with variation in response to ethyl hexanoate. Finally, differences in Or35a and Or47a expression were associated with variation in responses to ethyl hexanoate. These results demonstrate that the genetic variation at the peripheral sensory stage plays a role in mediating differences in odor-mediated behavior. PMID- 22038944 TI - Crypt neurons express a single V1R-related ora gene. AB - Both ciliated and microvillous olfactory sensory neuron populations express large families of olfactory receptor genes. However, individual neurons generally express only a single receptor gene according to the "one neuron-one receptor" rule. We report here that crypt neurons, the third type of olfactory neurons in fish species, use an even more restricted mode of expression. We recently identified a novel olfactory receptor family of 6 highly conserved G protein coupled receptors, the v1r-like ora genes. We show now that a single member of this family, ora4 is expressed in nearly all crypt neurons, whereas the other 5 ora genes are not found in this cell type. Consistent with these findings, ora4 is never coexpressed with any of the remaining 5 ora genes. Furthermore, several lines of evidence indicate the absence of any other olfactory receptor families in crypt neurons. These results suggest that the vast majority of the crypt neuron population may select one and the same olfactory receptor gene, a "one cell type-one receptor" mode of expression. Such an expression pattern is familiar in the visual system, with rhodopsin as the sole light receptor of rod photoreceptor cells, but unexpected in the sense of smell. PMID- 22038945 TI - The effects of capsaicin and capsiate on energy balance: critical review and meta analyses of studies in humans. AB - Consumption of spicy foods containing capsaicin, the major pungent principle in hot peppers, reportedly promotes negative energy balance. However, many individuals abstain from spicy foods due to the sensory burn and pain elicited by the capsaicin molecule. A potential alternative for nonusers of spicy foods who wish to exploit this energy balance property is consumption of nonpungent peppers rich in capsiate, a recently identified nonpungent capsaicin analog contained in CH-19 Sweet peppers. Capsiate activates transient receptor potential vanilloid subtype 1 (TRPV1) receptors in the gut but not in the oral cavity. This paper critically evaluates current knowledge on the thermogenic and appetitive effects of capsaicin and capsiate from foods and in supplemental form. Meta-analyses were performed on thermogenic outcomes, with a systematic review conducted for both thermogenic and appetitive outcomes. Evidence indicates that capsaicin and capsiate both augment energy expenditure and enhance fat oxidation, especially at high doses. Furthermore, the balance of the literature suggests that capsaicin and capsiate suppress orexigenic sensations. The magnitude of these effects is small. Purposeful inclusion of these compounds in the diet may aid weight management, albeit modestly. PMID- 22038946 TI - Biology-oriented synthesis. AB - Which compound classes are best suited as probes and tools for chemical biology research and as inspiration for medicinal chemistry programs? Chemical space is enormously large and cannot be exploited conclusively by means of synthesis efforts. Methods are required that allow one to identify and map the biologically relevant subspaces of vast chemical space, and serve as hypothesis-generating tools for inspiring synthesis programs. Biology-oriented synthesis builds on structural conservatism in the evolution of proteins and natural products. It employs a hierarchical classification of bioactive compounds according to structural relationships and type of bioactivity, and selects the scaffolds of bioactive molecule classes as starting points for the synthesis of compound collections with focused diversity. Navigation in chemical space is facilitated by Scaffold Hunter, an intuitively accessible and highly interactive software. Small molecules synthesized according to BIOS are enriched in bioactivity. They facilitate the analysis of complex biological phenomena by means of acute perturbation and may serve as novel starting points to inspire drug discovery programs. PMID- 22038947 TI - Ten tips for authors. PMID- 22038951 TI - Rapid eye movement sleep behavior disorder and subtypes in autopsy-confirmed dementia with Lewy bodies. AB - The purpose of this study was to determine whether dementia with Lewy bodies with and without probable rapid eye movement sleep behavior disorder differ clinically or pathologically. Patients with dementia with Lewy bodies (DLB) with probable rapid eye movement sleep behavior sleep disorder (n = 71) were compared with those without it (n = 19) on demographics, clinical variables (core features of dementia with Lewy bodies, dementia duration, rate of cognitive/motor changes), and pathologic indices (Lewy body distribution, neuritic plaque score, Braak neurofibrillary tangle stage). Individuals with probable rapid eye movement sleep behavior disorder were predominantly male (82% vs 47%) and had a shorter duration of dementia (mean, 8 vs 10 years), earlier onset of parkinsonism (mean, 2 vs 5 years), and earlier onset of visual hallucinations (mean, 3 vs 6 years). These patients also had a lower Braak neurofibrillary tangle stage (stage IV vs stage VI) and lower neuritic plaque scores (18% vs 85% frequency), but no difference in Lewy body distribution. When probable rapid eye movement sleep behavior disorder developed early (at or before dementia onset), the onset of parkinsonism and hallucinations was earlier and Braak neurofibrillary tangle stage was lower compared with those who developed the sleep disorder after dementia onset. Women with autopsy-confirmed DLB without a history of dream enactment behavior during sleep had a later onset of hallucinations and parkinsonism and a higher Braak NFT stage. Probable rapid eye movement sleep behavior disorder is associated with distinct clinical and pathologic characteristics of dementia with Lewy bodies. PMID- 22038953 TI - BMI alterations during treatment of childhood ALL-response. PMID- 22038952 TI - Drosophila cancer models. AB - Cancer is driven by complex genetic and cellular mechanisms. Recently, the Drosophila community has become increasingly interested in exploring cancer issues. The Drosophila field has made seminal contributions to many of the mechanisms that are fundamental to the cancer process; several of these mechanisms have already been validated in vertebrates. Less well known are the Drosophila field's early direct contributions to the cancer field: some of the earliest tumor suppressors were identified in flies. In this review, we identify major contributions that Drosophila studies have made toward dissecting the pathways and mechanisms underlying tumor progression. We also highlight areas, such as drug discovery, where we expect Drosophila studies to make a major scientific impact in the future. PMID- 22038954 TI - A general approach for the growth of metal oxide nanorod arrays on graphene sheets and their applications. AB - In the fabrication of flexible devices, highly ordered nanoscale texturing, such as semiconductor metal oxide nanorod arrays on flexible substrates, is critical for optimal performance. Use of transparent conducting films, metallic films, and polymer substrates is limited by mechanical brittleness, chemical and thermal instability, or low electrical conductivity, low melting point, and so on. A simple and general nanocrystal-seed-directed hydrothermal route has now been developed for large-scale growth of nanorod arrays of various semiconductor metal oxides (MO), including TiO(2), ZnO, MnO(2), CuO, and ZrO(2) on both sides of flexible graphene (G) sheets to form sandwichlike MO/G/MO heterostructures. The TiO(2)/G/TiO(2) heterostructures have much higher photocatalytic activity than TiO(2) nanorods, with a photocatalytic degradation rate of methylene blue that is four times faster than that of the TiO(2) nanorods, and are thus promising candidates for photocatalytic decontamination. PMID- 22038955 TI - Chilling with magnetic molecules. PMID- 22038956 TI - Light-induced electron transfer over distances of 5, 10, and 15 A within water filled yoctowells. AB - A small series of variable-depth yoctowell cavities with 'functional' walls on aminated silica particles and gold electrodes has been established. The dimensions of the gaps formed were 2.2 nm in diameter with varying 'functional' depths of 5, 10, and 15 A, depending on the length of bolaphiles applied and the position of the positive rim; these gaps were prepared through a Michael addition of the incorporated ene-amide groups. Using this construct and electrostatic interactions between the positive rim and anionic quinones as a means of immobilization, a porphyrin-quinone dyad system has been prepared. The distance between the donor and acceptor was changed systematically in aqueous solution, whilst maintaining a similar environment in each case. Upon photoexcitation of the porphyrin, efficient electron transfer occurs between the porphyrin and quinone units in a distance-dependent manner on the nanosecond timescale. PMID- 22038957 TI - Complete genome sequence of Bifidobacterium animalis subsp. lactis BLC1. AB - Bifidobacterium animalis subsp. lactis BLC1 is a probiotic bacterium that is widely exploited by food industries as the active ingredient of various functional foods. Here we report the complete genome sequence of B. animalis subsp. lactis BLC1, which is expected to provide insights into the biology of this health-promoting microorganism and improve our understanding of its phylogenetic relatedness with other members of the B. animalis subsp. lactis taxon. PMID- 22038958 TI - Complete genome sequence of the industrial strain Bacillus megaterium WSH-002. AB - Bacillus megaterium, an industrial strain, has been widely used in protein production and the vitamin C industry. Here we reported a finished, annotated, and compared 4.14-Mbp high-quality genome sequence of B. megaterium WSH-002, which is the companion strain for Ketogulonicigenium vulgare in the vitamin C industry and is stocked in our laboratory. PMID- 22038959 TI - Genome sequence of the diazotrophic Gram-positive rhizobacterium Paenibacillus riograndensis SBR5(T). AB - Paenibacillus riograndensis SBR5(T), a nitrogen-fixing Gram-positive rhizobacterium isolated from a wheat field in the south of Brazil, has a great potential for agricultural applications due to its plant growth promotion effects. Here we present the draft genome sequence of P. riograndensis SBR5(T). Its 7.37-Mb genome encodes determinants of the diazotrophic lifestyle and plant growth promotion, such as nitrogen fixation, antibiotic resistance, nitrate utilization, and iron uptake. PMID- 22038960 TI - Complete genome sequence of multidrug-resistant Acinetobacter baumannii strain 1656-2, which forms sturdy biofilm. AB - Acinetobacter baumannii is a Gram-negative bacterium causing nosocomial infections worldwide. To gain quick insight into the molecular basis of biofilm formation in A. baumannii, we determined the complete genome sequence of A. baumannii strain 1656-2, which forms sturdy biofilm and is resistant to multiple drugs. PMID- 22038961 TI - Complete genome sequence of the denitrifying and N(2)O-reducing bacterium Pseudogulbenkiania sp. strain NH8B. AB - Pseudogulbenkiania sp. strain NH8B is a Neisseriales bacterium isolated from an agricultural field. This strain has strong denitrification and N(2)O reduction activities. Here, we report the finished and annotated genome sequence of this organism. PMID- 22038962 TI - Genome sequence of multidrug-resistant Pseudomonas aeruginosa NCGM1179. AB - We report the annotated genome sequence of multidrug-resistant Pseudomonas aeruginosa strain NCGM1179, which is highly resistant to carbapenems, aminoglycosides, and fluoroquinolones and is emerging at medical facilities in Japan. PMID- 22038963 TI - Genome sequence of the thermophilic strain Bacillus coagulans XZL4, an efficient pentose-utilizing producer of chemicals. AB - Bacillus coagulans XZL4 is an efficient pentose-utilizing producer of important platform compounds, such as l-lactic acid, 2,3-butanediol, and acetoin. Here we present a 2.8-Mb assembly of its genome. Simple and efficient carbohydrate metabolism systems, especially the transketolase/transaldolase pathway, make it possible to convert pentose sugars to products at high levels. PMID- 22038964 TI - Genome sequence of Bacillus pumilus S-1, an efficient isoeugenol-utilizing producer for natural vanillin. AB - Bacillus pumilus S-1 is an efficient isoeugenol-utilizing producer of natural vanillin. The genome of B. pumilus S-1 contains the epoxide hydrolase and six candidate monooxygenases that make it possible to explore the mechanism involved in conversion of isoenguenol to vanillin in the B. pumilus strain. PMID- 22038965 TI - Genome sequence of the bacteriocin-producing oral probiotic Streptococcus salivarius strain M18. AB - Streptococcus salivarius is a Gram-positive bacterial commensal and pioneer colonizer of the human oral cavity. Many strains produce ribosomally synthesized proteinaceous antibiotics (bacteriocins), and some strains have been developed for use as oral probiotics. Here, we present the draft genome sequence of the bacteriocin-producing oral probiotic S. salivarius strain M18. PMID- 22038966 TI - Genome sequence of Sphingobium yanoikuyae XLDN2-5, an efficient carbazole degrading strain. AB - Sphingobium yanoikuyae XLDN2-5 is an efficient carbazole-degrading strain. Carbazole-degrading genes are accompanied on both sides by two copies of IS6100 elements. Here, we describe the draft genome sequence of strain XLDN2-5, which may provide important clues as to how it recruited exogenous genes to establish pathways to degrade the xenobiotics. PMID- 22038967 TI - Draft genome sequence of Escherichia coli XH001, a producer of L-threonine in industry. AB - L-Threonine has been widely used as a supplement in the food, pharmaceutical, and cosmetic industries. Here, we present a high-quality draft annotated genome sequence of Escherichia coli XH001, a producer of L-threonine in industry. Its genome and plasmid sequence will provide clues about the molecular mechanisms underlying its beneficial properties. PMID- 22038968 TI - Draft genome of Streptomyces zinciresistens K42, a novel metal-resistant species isolated from copper-zinc mine tailings. AB - A draft genome sequence of Streptomyces zinciresistens K42, a novel Streptomyces species displaying a high level of resistance to zinc and cadmium, is presented here. The genome contains a large number of genes encoding proteins predicted to be involved in conferring metal resistance. Many of these genes appear to have been acquired through horizontal gene transfer. PMID- 22038969 TI - Revised genome sequence of Brucella suis 1330. AB - Brucella suis is a causative agent of porcine brucellosis. We report the resequencing of the original sample upon which the published sequence of Brucella suis 1330 is based and describe the differences between the published assembly and our assembly at 12 loci. PMID- 22038970 TI - Complete genome sequences of Arcobacter butzleri ED-1 and Arcobacter sp. strain L, both isolated from a microbial fuel cell. AB - Arcobacter butzleri strain ED-1 is an exoelectrogenic epsilonproteobacterium isolated from the anode biofilm of a microbial fuel cell. Arcobacter sp. strain L dominates the liquid phase of the same fuel cell. Here we report the finished and annotated genome sequences of these organisms. PMID- 22038971 TI - Genome sequence of Serinicoccus profundi, a novel actinomycete isolated from deep sea sediment. AB - Serinicoccus profundi MCCC 1A05965(T) was isolated from deep-sea sediment collected from the Indian Ocean. It was a Gram-positive, moderately halophilic, aerobic bacterium. Here, we describe the 3.4-Mbp draft genome sequence of S. profundi MCCC 1A05965(T). PMID- 22038972 TI - Genome sequence of Lentibacillus jeotgali Grbi(T), isolated from traditional Korean salt-fermented seafood. AB - Lentibacillus jeotgali Grbi(T), isolated from a traditional Korean salt-fermented seafood, is a strictly aerobic, Gram-positive, nonmotile, endospore-forming, moderately halophilic bacterium belonging to the family Bacillaceae in the phylum Firmicutes. Here, the draft genome sequence of L. jeotgali Grbi(T) (3,775,822 bp with a G+C content of 42.5%) is reported. This is the first reported genome sequence from a Lentibacillus species. PMID- 22038973 TI - Genome sequence of Brachybacterium squillarum M-6-3(T), isolated from salt fermented seafood. AB - Brachybacterium squillarum M-6-3(T) was isolated from salt-fermented seafood in Korea and belongs to the Dermabacteraceae, a rather isolated family within the actinobacterial suborder Micrococcineae. Here, we present the draft genome sequence of the type strain Brachybacterium squillarum M-6-3(T) (3,191,479 bp), a Gram-positive bacterium with high (72.8%) G+C content. PMID- 22038974 TI - Whole-genome sequence of Corynebacterium pseudotuberculosis PAT10 strain isolated from sheep in Patagonia, Argentina. AB - In this work, we report the complete genome sequence of a Corynebacterium pseudotuberculosis PAT10 isolate, collected from a lung abscess in an Argentine sheep in Patagonia, whose pathogen also required an investigation of its pathogenesis. Thus, the analysis of the genome sequence offers a means to better understanding of the molecular and genetic basis of virulence of this bacterium. PMID- 22038975 TI - Genome sequence of Rhodococcus erythropolis XP, a biodesulfurizing bacterium with industrial potential. AB - Rhodococcus erythropolis strains have shown excellent characteristics in petroleum oil biodesulfurization. Here we present the first announcement of the draft genome sequence of an efficient biodesulfurizing bacterium named R. erythropolis XP (7,229,582 bp). The biodesulfurizing genes dszABC are located on a plasmid, while the flavin reductase gene dszD is located on the chromosome. PMID- 22038976 TI - Beneficial effects of mangiferin on hyperlipidemia in high-fat-fed hamsters. AB - SCOPE: Mangiferin, a natural polyphenol, has been shown to have hypolipidemic effect in rat and mouse. However, the mechanism of action is not well understood. This study was conducted to determine the effect and mechanism of action of mangiferin on hyperlipidemia induced in hamsters by a high-fat diet. METHODS AND RESULTS: Forty male hamsters were randomly assigned to normal control, high-fat control, and high fat with mangiferin (50 and 150 mg/kg BW) groups. Mangiferin treatment significantly decreased final body weight, liver weight and visceral fat-pad weight, serum triglyceride (TG) and total free fatty acid (FFA) concentrations, hepatic TG levels and hepatic and muscle total FFA contents. Mangiferin upregulated mRNA expression of peroxisome proliferator-activated receptor-alpha (PPAR-alpha), fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT-1), but downregulated mRNA expression of sterol regulatory element-binding protein 1c (SREBP-1c), acetyl CoA carboxylase (ACC), acyl-CoA:diacylglycerol acyltransferase 2 (DGAT-2) and microsomal triglyceride transfer protein (MTP) in liver. Mangiferin also stimulated mRNA expression of PPAR-alpha, CD36, CPT-1 and lipoprotein lipase (LPL) in muscle. CONCLUSIONS: The results suggest that mangiferin may ameliorate hypertriglyceridemia partly by modulating the expression levels of genes involved in lipid oxidation and lipogenesis. PMID- 22038977 TI - The extracellular region of Lrp4 is sufficient to mediate neuromuscular synapse formation. AB - Neuromuscular synapse formation requires an exchange of signals between motor neurons and muscle. Agrin, supplied by motor neurons, binds to Lrp4 in muscle, stimulating phosphorylation of MuSK and recruitment of a signaling complex essential for synapse-specific transcription and anchoring of key proteins in the postsynaptic membrane. Lrp4, like the LDLR and other Lrp-family members, contains an intracellular region with motifs that can regulate receptor trafficking, as well as assembly of an intracellular signaling complex. Here, we show that the intracellular region of Lrp4 is dispensable for Agrin to stimulate MuSK phosphorylation and clustering of acetylcholine receptors in cultured myotubes. Moreover, muscle-selective expression of a Lrp4-CD4 chimera, composed of the extracellular and transmembrane regions of Lrp4 and the intracellular region of CD4, rescues neuromuscular synapse formation and the neonatal lethality of lrp4 mutant mice, demonstrating that Lrp4, lacking the Lrp4 intracellular region, is sufficient for presynaptic and postsynaptic differentiation. PMID- 22038979 TI - Synthesis of copious amounts of SnS2 and SnS2/SnS nanotubes with ordered superstructures. PMID- 22038978 TI - In vitro sensitivity to dasatinib in lymphoblasts from a patient with t(17;19)(q22;p13) gene rearrangement pre-B acute lymphoblastic leukemia. AB - Patients with t(17;19) acute lymphoblastic leukemia (ALL) have a dismal prognosis even with the most intensive current therapies that include stem cell transplant. We present the case of a patient with t(17;19)(q22;p13) gene rearranged B-cell precursor ALL whose lymphoblasts were found to have significant in vitro sensitivity to dasatinib. The patient tolerated the addition of dasatinib with combination therapy and remained in remission for over nine months until his recurrence. Therefore, future studies will be needed to interrogate whether dasatinib has any therapeutic benefit in children with t(17;19) B-cell precursor ALL. PMID- 22038980 TI - Reversible molecular motion of a bis-calix[5]arene host driven by a photoresponsive guest. PMID- 22038981 TI - Auraptene regulates gene expression involved in lipid metabolism through PPARalpha activation in diabetic obese mice. AB - SCOPE: Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a key regulator of circulating lipid level. Thus, various food-derived compounds that activate PPARalpha as agonists have been screened and characterized. METHODS AND RESULTS: We investigated the effects of auraptene, a citrus-derived compound serving as a PPARalpha agonist in vitro, on abnormalities in lipid and glucose metabolisms. In high-fat-diet (HFD)-fed KK-Ay diabetic obese mice, auraptene treatment suppressed hyperlipidemia and triglyceride accumulation in the liver and skeletal muscle, and increased the mRNA expression levels of the PPARalpha target genes involved in fatty acid oxidation in the liver and skeletal muscle. Moreover, the adipocyte size in the auraptene-treated mice was significantly smaller than that in the control HFD-fed mice resulting in the improvement of HFD induced hyperglycemia and abnormalities in glucose tolerance. CONCLUSIONS: These findings indicate that auraptene activates PPARalpha also in vivo and its treatment may improve abnormalities in lipid and glucose metabolisms, suggesting that auraptene is a valuable food-derived compound for managing metabolic disorders. PMID- 22038982 TI - Smart foams: new perspectives towards responsive composite materials. PMID- 22038983 TI - Hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation in children: a nationwide survey in Japan. AB - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is associated with hypercytokinemia in children. Although HLH can be also observed after hematopoietic stem cell transplantation (HSCT), the incidence and clinical features of HLH after HSCT remain obscure. PROCEDURE: The clinical features of HLH after HSCT (post-HSCT HLH) were investigated in children with malignancies, immune deficiencies, or aplastic anemia. The HLH/Langerhans Cell Histiocytosis (LCH) Committee of the Japanese Society of Pediatric Hematology (JSPH) sent questionnaires to hospitals with JPSH members asking for details of cases in which HLH occurred after HSCT between 1998 and 2008. RESULTS: Among 42 children who were diagnosed with post-HSCT HLH between 1998 and 2008 in Japan, 37 fulfilled our inclusion criteria; of these, 26 were classified as early-onset (onset <30 days after HSCT) and 11 were classified as late-onset (onset >30 days after HSCT). In the early-onset group, the presence of respiratory symptoms, high levels of total bilirubin, and triglycerides at onset and the lack of control of GVHD with tacrolimus were significantly associated with non-resolution of HLH (P < 0.05). The survival rate was significantly higher in patients with resolution of HLH than in those without resolution (59% vs. 14%, P < 0.05). CONCLUSIONS: These findings suggest that early-onset post-HSCT HLH is a specific entity of HLH, and appropriate diagnosis and prompt management need to be established. PMID- 22038984 TI - Device performance and lifetime of polymer:fullerene solar cells with UV-ozone irradiated hole-collecting buffer layers. AB - We report the influence of UV-ozone irradiation of the hole-collecting buffer layers on the performance and lifetime of polymer:fullerene solar cells. UV-ozone irradiation was targeted at the surface of the poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) layers by varying the irradiation time up to 600 s. The change of the surface characteristics in the PEDOT:PSS after UV-ozone irradiation was measured by employing optical absorption spectroscopy, photoelectron yield spectroscopy, and contact angle measurements, while Raman and X-ray photoelectron spectroscopy techniques were introduced for more microscopic analysis. Results showed that the UV-ozone irradiation changed the chemical structure/composition of the surface of the PEDOT:PSS layers leading to the gradual increase of ionization potential with irradiation time in the presence of up-and-down variations in the contact angle (polarity). This surface property change was attributed to the formation of oxidative components, as evidenced by XPS and Auger electron images, which affected the sheet resistance of the PEDOT:PSS layers. Interestingly, device performance was slightly improved by short irradiation (up to 10 s), whereas it was gradually decreased by further irradiation. The short-duration illumination test showed that the lifetime of solar cells with the UV-ozone irradiated PEDOT:PSS layer was improved due to the protective role of the oxidative components formed upon UV-ozone irradiation against the attack of sulfonic acid groups in the PEDOT:PSS layer to the active layer. PMID- 22038985 TI - Autumn fog. PMID- 22038986 TI - Distribution of inflammation within carotid atherosclerotic plaques with high risk morphological features: a comparison between positron emission tomography activity, plaque morphology, and histopathology. AB - BACKGROUND: Several high-risk morphological features (HRM) of plaques, especially in combination, are associated with an increased risk of a clinical event. Although plaque inflammation is also associated with atherothrombosis, the relationship between inflammation and number of HRM is not well understood. METHODS AND RESULTS: Thirty-four patients underwent (18)flurodeoxyglucose positron emission tomography (FDG-PET) imaging, and carotid atherosclerotic inflammation was assessed (target-to- BACKGROUND: =0.0003) and increased with the number of HRM observed (P<0.001 for trend). Similarly, inflammation within atherosclerotic specimens (% CD68 staining) was higher in plaques with (versus without) HRM (median [interquartile range]: 10 [0, 19.85] versus 0 [0, 1.55], P=0.01) and increased with the number of HRM observed (P<0.001 for trend). CONCLUSIONS: Inflammation, as assessed by both FDG uptake and histology, is increased in plaques containing HRM and increases with increasing number of HRM. These data support the concept that inflammation accumulates relative to the burden of morphological abnormalities. PMID- 22038987 TI - Utility of cardiovascular magnetic resonance in identifying substrate for malignant ventricular arrhythmias. AB - BACKGROUND: Sudden cardiac death (SCD) and sustained monomorphic ventricular tachycardia (SMVT) are frequently associated with prior or acute myocardial injury. Cardiovascular magnetic resonance (CMR) provides morphological, functional, and tissue characterization in a single setting. We sought to evaluate the diagnostic yield of CMR-based imaging versus non-CMR-based imaging in patients with resuscitated SCD or SMVT. METHODS AND RESULTS: Eighty-two patients with resuscitated SCD or SMVT underwent routine non-CMR imaging, followed by a CMR protocol with comprehensive tissue characterization. Clinical reports of non-CMR imaging studies were blindly adjudicated and used to assign each patient to 1 of 7 diagnostic categories. CMR imaging was blindly interpreted using a standardized algorithm used to assign a patient diagnosis category in a similar fashion. The diagnostic yield of CMR-based and non-CMR-based imaging, as well as the impact of the former on diagnosis reclassification, was established. Relevant myocardial disease was identified in 51% of patients using non-CMR-based imaging and in 74% using CMR-based imaging (P=0.002). Forty-one patients (50%) were reassigned to a new or alternate diagnosis using CMR-based imaging, including 15 (18%) with unsuspected acute myocardial injury. Twenty patients (24%) had no abnormality by non-CMR imaging but showed clinically relevant myocardial disease by CMR imaging. CONCLUSIONS: CMR-based imaging provides a robust diagnostic yield in patients presenting with resuscitated SCD or SMVT and incrementally identifies clinically unsuspected acute myocardial injury. When compared with non-CMR-based imaging, a new or alternate myocardial disease process may be identified in half of these patients. PMID- 22038988 TI - Improved detection of myocardial involvement in acute inflammatory cardiomyopathies using T2 mapping. AB - BACKGROUND: T2-weighted cardiac magnetic resonance imaging is useful in diagnosing acute inflammatory myocardial diseases, such as myocarditis and tako tsubo cardiomyopathy (TTCM). We hypothesized that quantitative T2 mapping could better delineate myocardial involvement in these disorders versus T2-weighted imaging. METHODS AND RESULTS: Thirty patients with suspected myocarditis or TTCM, referred for cardiac magnetic resonance imaging, who met established diagnostic criteria underwent myocardial T2 mapping. T2 values were averaged in involved and remote myocardial segments, both defined by a reviewer blinded to T2 data. In myocarditis, T2 was 65.2+/-3.2 ms in the involved myocardium versus 53.5+/-2.1 ms in the remote myocardium (P<0.001). In TTCM, T2 was 65.6+/-4.0 ms in the involved myocardium versus 53.6+/-2.7 ms in the remote segments (P<0.001). T2 values were similar across remote myocardial segments in patients and all myocardial segments in controls (P>0.05 for all). T2 maps provided diagnostic data even in patients with difficulty breath holding. A T2 cutoff of 59 ms identified areas of myocardial involvement, with sensitivity and specificity of 94% and 97%, respectively. T2 mapping revealed regions of abnormal T2 beyond those identified by wall motion abnormalities or late gadolinium-enhancement positivity. Conventional T2-weighted short tau inversion recovery images were uninterpretable in 7 patients because of artifact and unremarkable in 2 patients who had elevated T2 values. T2-prepared steady-state-free precession images showed areas of signal hyperintensity in only 17 of 30 patients. CONCLUSIONS: Quantitative T2 mapping reliably identifies myocardial involvement in patients with myocarditis and TTCM. T2 mapping delineated a greater extent of myocardial disease in both conditions compared with that identified by wall motion abnormalities, T2-weighted short tau inversion recovery imaging, T2-prepared steady-state-free precession, or late gadolinium enhancement. Quantitative T2 mapping warrants consideration as a robust technique to identify myocardial injury in patients with acute myocarditis or TTCM. PMID- 22038989 TI - Physiology and Endocrinology Symposium: How single nucleotide polymorphism chips will advance our knowledge of factors controlling puberty and aid in selecting replacement beef females. AB - The promise of genomic selection is accurate prediction of the genetic potential of animals from their genotypes. Simple DNA tests might replace low-accuracy predictions for expensive or lowly heritable measures of puberty and fertility based on performance and pedigree. Knowing with some certainty which DNA variants (e.g., SNP) affect puberty and fertility is the best way to fulfill the promise. Several SNP from the BovineSNP50 assay have tentatively been associated with reproductive traits including age at puberty, antral follicle count, and pregnancy observed on different sets of heifers. However, sample sizes are too small and SNP density is too sparse to definitively determine genomic regions harboring causal variants affecting reproductive success. Additionally, associations between individual SNP and similar phenotypes are inconsistent across data sets, and genomic predictions do not appear to be globally applicable to cattle of different breeds. Discrepancies may be a result of different QTL segregating in the sampled populations, differences in linkage disequilibrium (LD) patterns such that the same SNP are not correlated with the same QTL, and spurious correlations with phenotype. Several approaches can be used independently or in combination to improve detection of genomic factors affecting heifer puberty and fertility. Larger samples and denser SNP will increase power to detect real associations with SNP having more consistent LD with underlying QTL. Meta-analysis combining results from different studies can also be used to effectively increase sample size. High-density genotyping with heifers pooled by pregnancy status or early and late puberty can be a cost-effective means to sample large numbers. Networks of genes, implicated by associations with multiple traits correlated with puberty and fertility, could provide insight into the complex nature of these traits, especially if corroborated by functional annotation, established gene interaction pathways, and transcript expression. Example analyses are provided to demonstrate how integrating information about gene function and regulation with statistical associations from whole-genome SNP genotyping assays might enhance knowledge of genomic mechanisms affecting puberty and fertility, enabling reliable DNA tests to guide heifer selection decisions. PMID- 22038990 TI - Triennial Lactation Symposium: Opportunities for improving milk production efficiency in dairy cattle. AB - Increasing feed costs and the desire to improve environmental stewardship have stimulated renewed interest in improving feed efficiency of livestock, including that of US dairy herds. For instance, USDA cost projections for corn and soybean meal suggest a 20% increase over 2010 pricing for a 16% protein mixed dairy cow ration in 2011, which may lead to a reduction in cow numbers to maintain profitability of dairy production. Furthermore, an October 2010 study by The Innovation Center for US Dairy to assess the carbon footprint of fluid milk found that the efficiency of feed conversion is the single greatest factor contributing to variation in the carbon footprint because of its effects on methane release during enteric fermentation and from manure. Thus, we are conducting research in contemporary US Holsteins to identify cows most efficient at converting feed to milk in temperate climates using residual feed intake (RFI), a measure used successfully to identify the beef cattle most efficient at converting feed to gain. Residual feed intake is calculated as the difference between predicted and actual feed intake to support maintenance and production (e.g., growth in beef cattle, or milk in dairy cattle). Heritability estimates for RFI in dairy cattle reported in the literature range from 0.01 to 0.38. Selection for a decreased RFI phenotype can reduce feed intake, methane production, nutrient losses in manure, and visceral organ weights substantially in beef cattle. We have estimated RFI during early lactation (i.e., to 90 d in milk) in the Beltsville Agricultural Research Center Holstein herd and observed a mean difference of 3.7 kg/d (P < 0.0001) in actual DMI between the efficient and inefficient groups (+/-0.5 SD from the mean RFI of 0), with no evidence of differences (P > 0.20) in mean BW, ADG, or energy-corrected milk exhibited between the 2 groups. These results indicate promise for using RFI in dairy cattle to improve feed conversion to milk. Previous and current research on the use of RFI in lactating dairy cattle are discussed, as well as opportunities to improve production efficiency of dairy cattle using RFI for milk production. PMID- 22038991 TI - Cell Biology Symposium: Zinc finger nucleases to create custom-designed modifications in the swine (Sus scrofa) genome. AB - Engineered zinc finger nucleases (ZFN) are rapidly gaining popularity as a means to enhance the rate and specificity of DNA modifications in plant and animal cells. Repair-mediated gene modification by ZFN is driven by introducing DNA double-strand breaks via a nonspecific nuclease domain linked to a sequence specific zinc finger nucleotide recognition domain. This review examines the use of ZFN to produce genetically modified swine and the potential of this technology for the future. By combining conventional gene targeting methods with somatic cell nuclear transfer, several genetically modified pig models have been produced. These conventional techniques are inefficient in mammalian somatic cells and provide little control over the site specificity and rate of exogenous DNA integration. The use of engineered ZFN that bind and cleave genomic DNA at specific loci can enhance targeting efficiencies by orders of magnitude. Recent publication of the first genetic modification in pigs by combining ZFN technology with somatic cell nuclear transfer has opened the door to genome targeting with a precision that was not previously possible in a large animal model. Since that time, model pigs with selective knockout of endogenous genes have been produced. This review will examine the use of ZFN to generate these pig models and the potential of ZFN to accelerate the production of genetically modified pigs of agricultural and biomedical importance. Current methods of ZFN design, important considerations for their safe and effective use in modification of the swine genome, and future innovative applications of this technology in pigs will be discussed. PMID- 22038992 TI - Effect of dietary crude glycerol level on ruminal fermentation in continuous culture and growth performance of beef calves. AB - Continuous culture and in vivo experiments were conducted to measure changes in ruminal fermentation and animal performance when crude glycerol was added to diets. For the continuous culture experiment (n = 6), diets consisted of 4 levels of crude glycerol (0, 5, 10, and 20%) that replaced corn grain. Dry matter and OM digestibility decreased linearly (P < 0.05) when crude glycerol increased in the diet, and no effect (P = 0.20 and 0.65, respectively) was observed for CP and NDF digestibility. Total VFA concentration and ammonia did not change (P > 0.05) due to crude glycerol level. Microbial efficiency increased quadratically (P = 0.012) as crude glycerol increased, whereas microbial N flow did not differ (P = 0.36) among treatments. As crude glycerol increased in the diet, crude glycerol digestibility decreased (P < 0.05). Seventy-two crossbred steer calves (250 +/- 2.0 kg) were assigned to 4 treatments: 0, 5, 10, and 20% crude glycerol that replaced corn grain. Animals were fed for a total of 150 d. No differences (P = 0.08) between treatments were measured for DMI. Average daily gain and GF responded quadratically (P < 0.05), with 10% crude glycerol resulting in the greatest values. In the second in vivo experiment, 100 crossbred steer calves (300 +/- 2.0 kg) were assigned to 5 treatments: 0, 5, 10, 12.5, or 15% crude glycerol replaced corn grain. Calves were fed for a total of 135 d. No significant differences (P > 0.05) were measured in growth performance. For Exp. 3, one hundred heifer calves (270 +/- 2.0 kg) were assigned to 4 treatments: 0, 5, 10, or 20% crude glycerol that replaced hay. No differences (P > 0.05) were measured in animal performance. We concluded that crude glycerol addition to a diet did not negatively affect ruminal fermentation, and addition of up to 20% in concentrate and hay-based diets should not affect performance or carcass characteristics. PMID- 22038993 TI - Predicting IGF-1R therapy response in bone sarcomas: immuno-SPECT imaging with radiolabeled R1507. AB - PURPOSE: To investigate whether indium-111-labeled R1507 ((111)In-R1507) immuno SPECT (single-photon emission computed tomography), a novel noninvasive, in vivo screening method to visualize membranous insulin-like growth factor 1 receptor (IGF-1R) expression and accessibility, can be used to predict IGF-1R treatment (R1507) response in bone sarcomas. EXPERIMENTAL DESIGN: BALB/c nude mice were subcutaneously implanted with IGF-1R-expressing human bone sarcoma xenografts (OS 1, EW-5, and EW-8) which showed high, modest, or no response, respectively, to R1507, a monoclonal antibody targeting the extracellular domain of IGF-1R. An IGF 1R-negative tumor (OS-33), unresponsive to IGF-1R inhibitors, was examined as well. Mice were injected with (111)In-R1507. Biodistribution and immuno SPECT/computed tomography imaging studies were carried out 1, 3, and 7 days p.i. in mice with OS-1 and EW-5 xenografts and 3 days p.i. in mice with EW-8 and OS-33 xenografts. RESULTS: Biodistribution studies showed specific accumulation of (111)In-R1507 in OS-1 and EW-5 xenografts (27.5 +/- 6.5%ID/g and 14.0 +/- 2.8%ID/g, 3 days p.i., respectively). Most importantly, (111)In-R1507 uptake in IGF-1R positive, but unresponsive, EW-8 xenografts (6.5 +/- 1.5%ID/g, 3 days p.i.) was similar to that of the IGF-1R-negative OS-33 tumor (5.5 +/- 0.6%ID/g, 3 days p.i.). Uptake in normal tissues was low and nonspecific. Corresponding immuno-SPECT images clearly discriminated between high, modest, and nonresponding tumors by showing a homogeneous (OS-1), heterogeneous (EW-5), or nonspecific (EW 8 and OS-33) tumor uptake of (111)In-R1507. CONCLUSIONS: (111)In-R1507 immuno SPECT is an excellent method to visualize membranous IGF-1R expression and target accessibility in vivo in human bone sarcoma xenografts and may serve as an independent marker to predict IGF-1R therapy (R1507) response in bone sarcoma patients. PMID- 22038994 TI - Histone deacetylase inhibitors induce growth arrest and differentiation in uveal melanoma. AB - PURPOSE: Metastasis is responsible for the death of most cancer patients, yet few therapeutic agents are available which specifically target the molecular events that lead to metastasis. We recently showed that inactivating mutations in the tumor suppressor gene BAP1 are closely associated with loss of melanocytic differentiation in uveal melanoma (UM) and metastasis. The purpose of this study was to identify therapeutic agents that reverse the phenotypic effects of BAP1 loss in UM. EXPERIMENTAL DESIGN: In silico screens were done to identify therapeutic compounds predicted to differentiate UM cells using Gene Set Enrichment Analysis and Connectivity Map databases. Valproic acid (VPA), trichostatin A, LBH-589, and suberoylanilide hydroxamic acid were evaluated for their effects on UM cells using morphologic evaluation, MTS viability assays, bromodeoxyuridine incorporation, flow cytometry, clonogenic assays, gene expression profiling, histone acetylation and ubiquitination assays, and a murine xenograft tumorigenicity model. RESULTS: Histone deacetylase (HDAC) inhibitors induced morphologic differentiation, cell-cycle exit, and a shift to a differentiated, melanocytic gene expression profile in cultured UM cells. VPA inhibited the growth of UM tumors in vivo. CONCLUSIONS: These findings suggest that HDAC inhibitors may have therapeutic potential for inducing differentiation and prolonged dormancy of micrometastatic disease in UM. PMID- 22038995 TI - Use of [11C]choline PET-CT as a noninvasive method for detecting pelvic lymph node status from prostate cancer and relationship with choline kinase expression. AB - PURPOSE: To evaluate the accuracy and biological basis for [(11)C]choline-PET-CT in the nodal staging of high risk localized prostate cancer patients. EXPERIMENTAL DESIGN: Twenty-eight patients underwent dynamic [(11)C]choline-PET CT of the pelvis and lower abdomen prior to extended laparoscopic pelvic lymph node dissection (eLPL). The sensitivity and specificity of [(11)C]choline PET, [(11)C]choline PET-CT, and MRI for nodal detection were calculated. Average and maximal standardized uptake values (SUV(ave), SUV(max)) were compared with choline kinase alpha (CHKalpha) and Ki67 immunohistochemistry scores. RESULTS: Four hundred and six lymph nodes (LN), in 26 patients, were assessable. Twenty seven (6.7%) involved pelvic nodes at eLPL were detected in 9 patients. Seventeen of the 27 involved nodes were subcentimeter. The sensitivity and specificity on a per nodal basis were 18.5% and 98.7%, 40.7% and 98.4%, and 51.9% and 98.4% for MRI, [(11)C]choline PET, and [(11)C]choline PET-CT, respectively. Sensitivity was higher for [(11)C]choline PET-CT compared with MRI (P = 0.007). A higher nodal detection rate, including subcentimeter nodes, was seen with [(11)C]choline PET CT than MRI. Malignant lesions showed CHKalpha expression in both cytoplasm and nucleus. SUV(ave) and SUV(max) strongly correlated with CHKalpha staining intensity (r = 0.68, P < 0.0001 and r = 0.63, P = 0.0004, respectively). In contrast, Ki67 expression was generally low in all tumors. CONCLUSION: This study establishes the relationship between [(11)C]choline PET-CT uptake with choline kinase expression in prostate cancer and allows it to be used as a noninvasive means of staging pelvic LNs, being highly specific and more sensitive than MRI, including the detection of subcentimeter disease. PMID- 22038996 TI - Targeted therapy for BRAFV600E malignant astrocytoma. AB - PURPOSE: Malignant astrocytomas (MA) are aggressive central nervous system tumors with poor prognosis. Activating mutation of BRAF (BRAF(V600E)) has been reported in a subset of these tumors, especially in children. We have investigated the incidence of BRAF(V600E) in additional pediatric patient cohorts and examined the effects of BRAF blockade in preclinical models of BRAF(V600E) and wild-type BRAF MA. EXPERIMENTAL DESIGN: BRAF(V600E) mutation status was examined in two pediatric MA patient cohorts. For functional studies, BRAF(V600E) MA cell lines were used to investigate the effects of BRAF shRNA knockdown in vitro, and to investigate BRAF pharmacologic inhibition in vitro and in vivo. RESULTS: BRAF(V600E) mutations were identified in 11 and 10% of MAs from two distinct series of tumors (six of 58 cases total). BRAF was expressed in all MA cell lines examined, among which BRAF(V600E) was identified in four instances. Using the BRAF(V600E)-specific inhibitor PLX4720, pharmacologic blockade of BRAF revealed preferential antiproliferative activity against BRAF(V600E) mutant cells in vitro, in contrast to the use of shRNA-mediated knockdown of BRAF, which inhibited cell growth of glioma cell lines regardless of BRAF mutation status. Using orthotopic MA xenografts, we show that PLX4720 treatment decreases tumor growth and increases overall survival in mice-bearing BRAF(V600E) mutant xenografts, while being ineffective, and possibly tumor promoting, against xenografts with wild-type BRAF. CONCLUSIONS: Our results indicate a 10% incidence of activating BRAF(V600E) among pediatric MAs. With regard to implications for therapy, our results support evaluation of BRAF(V600E)-specific inhibitors for treating BRAF(V600E) MA patients. PMID- 22038997 TI - Pharmacodynamic study using FLT PET/CT in patients with renal cell cancer and other solid malignancies treated with sunitinib malate. AB - PURPOSE: To characterize proliferative changes in tumors during the sunitinib malate exposure/withdrawal using 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging. PATIENTS AND METHODS: Patients with advanced solid malignancies and no prior anti-VEGF exposure were enrolled. All patients had metastatic lesions amenable to FLT PET/CT imaging. Sunitinib was initiated at the standard dose of 50 mg p.o. daily either on a 4/2 or 2/1 schedule. FLT PET/CT scans were obtained at baseline, during sunitinib exposure, and after sunitinib withdrawal within cycle #1 of therapy. VEGF levels and sunitinib pharmacokinetic (PK) data were assessed at the same time points. RESULTS: Sixteen patients (8 patients on 4/2 schedule and 8 patients on 2/1 schedule) completed all three planned FLT PET/CT scans and were evaluable for pharmacodynamic imaging evaluation. During sunitinib withdrawal (change from scans 2 to 3), median FLT PET standardized uptake value (SUV(mean)) increased +15% (range: -14% to 277%; P = 0.047) for the 4/2 schedule and +19% (range: -5.3% to 200%; P = 0.047) for the 2/1 schedule. Sunitinib PK and VEGF ligand levels increased during sunitinib exposure and returned toward baseline during the treatment withdrawal. CONCLUSIONS: The increase of cellular proliferation during sunitinib withdrawal in patients with renal cell carcinoma and other solid malignancies is consistent with a VEGF receptor (VEGFR) tyrosine kinase inhibitor (TKI) withdrawal flare. Univariate and multivariate analysis suggest that plasma VEGF is associated with this flare, with an exploratory analysis implying that patients who experience less clinical benefit have a larger withdrawal flare. This might suggest that patients with a robust compensatory response to VEGFR TKI therapy experience early "angiogenic escape." PMID- 22038998 TI - Gluconacetobacter tumulicola sp. nov. and Gluconacetobacter asukensis sp. nov., isolated from the stone chamber interior of the Kitora Tumulus. AB - Six Gram-negative, rod-shaped, non-spore-forming bacterial strains were isolated from small holes on plaster walls of the stone chamber interior of the Kitora Tumulus in Asuka village, Nara Prefecture, Japan. These were investigated by means of a polyphasic approach. All the isolates were strictly aerobic and motile by peritrichous flagella. Phylogenetic trees generated based on 16S rRNA gene sequences identified two novel lineages (comprising five isolates and one isolate, respectively) within the genus Gluconacetobacter. The isolates were characterized by having Q-10 as the major ubiquinone system and C(18:1)omega7c (58.7-63.1% of the total) as the predominant fatty acid. DNA-DNA hybridization experiments endorsed the species rank for the two lineages, for which the names Gluconacetobacter tumulicola sp. nov. (type strain K5929-2-1b(T) = JCM 17774(T) = NCIMB 14760(T)) and Gluconacetobacter asukensis sp. nov. (type strain K8617-1 1b(T) = JCM 17772(T) = NCIMB 14759(T)) are proposed. PMID- 22038999 TI - Amphibacillus cookii sp. nov., a facultatively aerobic, spore-forming, moderately halophilic, alkalithermotolerant bacterium. AB - Novel strains of facultatively aerobic, moderately alkaliphilic and facultatively halophilic bacteria were isolated from a sediment sample taken from the Southern Arm of Great Salt Lake, Utah. Cells of strain JW/BP-GSL-QD(T) (and related strains JW/BP-GSL-RA and JW/BP-GSL-WB) were rod-shaped, spore-forming, motile bacteria with variable Gram-staining. Strain JW/BP-GSL-QD(T) grew under aerobic conditions between 14.5 and 47 degrees C (optimum 39 degrees C), in the pH(37 degrees C) range 6.5-10.3 (optimum pH(37 degrees C) 8.0), and between 0.1 and 4.5 M Na(+) (optimum 0.9 M Na(+)). No growth was observed in the absence of supplemented Na(+). Strain JW/BP-GSL-QD(T) utilized L-arabinose, D-fructose, D galactose, D-glucose, inulin, lactose, maltose, mannitol, D-mannose, pyruvate, D ribose, D-sorbitol, starch, trehalose, xylitol and D-xylose under both aerobic and anaerobic conditions, and used ethanol and methanol only under aerobic conditions. Strains JW/BP-GSL-WB and JW/BP-GSL-RA had the same profiles except that methanol was not used aerobically. During growth on glucose, the major organic compounds formed under aerobic conditions were acetate and lactate, and under anaerobic conditions, the fermentation products were formate, acetate, lactate and ethanol. Oxidase and catalase activities were not detected and cytochrome was absent. No respiratory quinones were detected. The main cellular fatty acids were iso-C(15 : 0) (39.1 %) and anteiso-C(15 : 0) (36.3 %). Predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unknown phospholipid. Additionally, a small amount of an unknown glycolipid was detected. The DNA G+C content of strain JW/BP-GSL-QD(T) was 35.4 mol% (determined by HPLC). For strain JW/BP-GSL-QD(T) the highest degree of 16S rRNA gene sequence similarity was found with Amphibacillus jilinensis (98.6 %), Amphibacillus sediminis (96.7 %) and Amphibacillus tropicus (95.6 %). The level of DNA-DNA relatedness between strain JW/BP-GSL-QD(T) and A. jilinensis Y1(T) was 58 %. On the basis of physiological, chemotaxonomic and phylogenetic data, strain JW/BP GSL-QD(T) represents a novel species of the genus Amphibacillus, for which the name Amphibacillus cookii sp. nov. is proposed. The type strain is JW/BP-GSL QD(T) (= ATCC BAA-2118(T) = DSM 23721(T)). PMID- 22039000 TI - Candidimonas bauzanensis sp. nov., isolated from soil, and emended description of the genus Candidimonas Vaz-Moreira et al. 2011. AB - A Gram-negative, facultatively anaerobic, psychrophilic, motile rod, designated BZ59(T), was isolated from hydrocarbon-contaminated soil. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain BZ59(T) belonged to the genus Candidimonas and had highest 16S rRNA gene sequence similarity with Candidimonas nitroreducens SC-089(T) (97.7 %) and Candidimonas humi SC-092(T) (97.6 %). The ubiquinone was Q-8 and the major fatty acids were C(16 : 0), C(17 : 0) cyclo and summed feature 3 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH). The polar lipid profile contained the major compounds phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmonomethylethanolamine and diphosphatidylglycerol. The major polyamines were putrescine and spermidine; a minor amount of 2-hydroxyputrescine was present. The DNA G+C content of strain BZ59(T) was 61.6 mol%. Combined data from phenotypic, phylogenetic and DNA-DNA relatedness studies demonstrated that strain BZ59(T) represents a novel species of the genus Candidimonas, for which the name Candidimonas bauzanensis sp. nov. is proposed. The type strain is BZ59(T) (= DSM 22805(T) = LMG 26046(T) = CGMCC 1.10190(T)). The description of the genus Candidimonas is emended. PMID- 22039001 TI - Vibrio xiamenensis sp. nov., a cellulase-producing bacterium isolated from mangrove soil. AB - A taxonomic study was carried out on a cellulase-producing bacterium, strain G21(T), isolated from mangrove soil in Xiamen, Fujian province, China. Cells were Gram-negative, slightly curved rods, motile with a single polar flagellum. The strain grew at 15-40 degrees C and in 0.5-10% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain G21(T) belonged to the genus Vibrio and formed a clade with Vibrio furnissii ATCC 350116(T) (97.4% sequence similarity), V. fluvialis LMG 7894(T) (97.1%) and V. ponticus CECT 5869(T) (96.1%). However, multilocus sequence analysis (using rpoA, recA, mreB, gapA, gyrB and pyrH sequences) and DNA-DNA hybridization experiments indicated that the strain was distinct from the closest related Vibrio species. Additionally, strain G21(T) could be differentiated from them phenotypically by the ability to grow in 10% NaCl but not on TCBS plates, its enzyme activity spectrum, citrate utilization, oxidization of various carbon sources, hydrolysis of several substrates and its cellular fatty acid profile. The G+C content of the genomic DNA was 46.0 mol%. The major cellular fatty acids were summed feature 3 (C(16:1)omega7c and/or iso-C(15:0) 2-OH), C(16:0) and C(18:1)omega7c. The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol, with trace amounts of diphosphatidylglycerol. The predominant quinones were Q-8 and Q-7. Based on phylogenetic, phenotypic and chemotaxonomic characteristics and DNA-DNA hybridization analysis, it is concluded that strain G21(T) represents a novel species of the genus Vibrio, for which the name Vibrio xiamenensis sp. nov. is proposed. The type strain is G21(T) ( = DSM 22851(T) = CGMCC 1.10228(T)). PMID- 22039002 TI - Desulfonatronobacter acidivorans gen. nov., sp. nov. and Desulfobulbus alkaliphilus sp. nov., haloalkaliphilic heterotrophic sulfate-reducing bacteria from soda lakes. AB - Two types of heterotrophic sulfate-reducing bacteria (SRB) were isolated from anoxic sediments of hypersaline soda lakes in Kulunda Steppe (Altai, Russia). The isolates used propionate as an energy and carbon source. Strain APT2(T) was enriched and isolated with thiosulfate as the electron acceptor. Strains APS1(T) and ASS1 were isolated with sulfate. Strain APT2(T) was a short rod and motile with a single subpolar flagellum, while strains APS1(T) and ASS1 were lemon shaped oval rods and motile with a single polar flagellum and thin flagella-like filaments. Strain APT2(T) grew by complete oxidation of C(3)-C(8) fatty acids with thiosulfate or sulfate as the electron acceptor, while strains APS1(T) and ASS1 were much less versatile and utilized only propionate and pyruvate as the electron donor and carbon source with sulfate or sulfite as the electron acceptor. Furthermore, strains APS1(T) and ASS1 oxidized propionate incompletely to form acetate. All of the isolates were moderately halophilic and obligately alkaliphilic. Phylogenetic analysis based on 16S rRNA gene sequences placed the isolates in the order Desulfobacterales of the class Deltaproteobacteria. Strain APT2(T) belonged to the family Desulfobacteraceae and clustered with a halophilic SRB, Desulfosalsimonas propionicica PropA(T). Strains APS1(T) and ASS1 were closely related to each other and clustered with the genus Desulfobulbus of the family Desulfobulbaceae. On the basis of phenotypic and phylogenetic analysis, the isolates are proposed to represent two novel taxa, Desulfonatronobacter acidivorans gen. nov., sp. nov. (type strain of the type species APT2(T) = DSM 24257(T) = UNIQEM U853(T)) and Desulfobulbus alkaliphilus sp. nov. (type strain APS1(T) = DSM 24258(T) = UNIQEM U900(T)). PMID- 22039003 TI - Brevibacillus nitrificans sp. nov., a nitrifying bacterium isolated from a microbiological agent for enhancing microbial digestion in sewage treatment tanks. AB - A heterotrophic nitrifying bacterium, designated strain DA2(T), was isolated from a microbiological agent for enhancing microbial digestion in sewage treatment tanks. Cells of strain DA2(T) were Gram-positive, facultatively anaerobic, sporulating rods that were motile by means of peritrichous flagella; they were able to grow at pH 5-8. The major isoprenoid quinone of strain DA2(T) was menaquinone-7 (MK-7) and its cellular fatty acid profile consisted mainly of iso C(15 : 0) (18.6 %) and anteiso-C(15 : 0) (69.1 %). The DNA G+C content was 54.1 mol%. 16S rRNA gene sequence phylogeny suggested that strain DA2(T) is a member of the genus Brevibacillus, with highest sequence similarities (in parentheses) to the type strains of Brevibacillus choshinensis (99.7 %), B. formosus (99.4 %), B. brevis (99.4 %), B. agri (99.0 %), B. reuszeri (98.8 %), B. parabrevis (98.7 %), B. centrosporus (98.6 %), B. limnophilus (97.4 %), B. panacihumi (97.3 %) and B. invocatus (97.3 %). DNA-DNA hybridization showed less than 60 % relatedness between strain DA2(T) and type strains of the most closely related species given above. Given the significant differences in phenotypic and chemotaxonomic characteristics, and phylogenetic analysis based on the 16S rRNA sequence and DNA DNA relatedness data, the isolate merits classification as a novel species, for which the name Brevibacillus nitrificans is proposed; the type strain of this species is DA2(T) (= JCM 15774(T) = NCIMB 14531(T)). PMID- 22039004 TI - Cyclobacterium qasimii sp. nov., a psychrotolerant bacterium isolated from Arctic marine sediment. AB - A novel Gram-stain-negative, horseshoe-shaped, non-motile bacterium, designated strain M12-11B(T), was isolated from a marine sediment sample collected at a depth of 200 m from Kongsfjorden, Svalbard. The colony colour was orangish red due to the presence of carotenoids. Fatty acids were dominated by branched and unsaturated fatty acids (90.8 %), with a high abundance of iso-C(15 : 0) (14.9 %), anteiso-C(15 : 0) (11.4 %), iso-C(15 : 1) G (13.1 %), C(15 : 1)omega6c (5.4 %), C(17 : 1)omega6c (6.7 %), summed feature 3 (C(16 : 1)omega7c and/or C(16 : 1)omega6c; 9.3 %) and summed feature 9 (10-methyl C(16 : 0) and/or iso-C(17 : 1)omega9c; 5.9 %). Strain M12-11B(T) contained MK-7 as the major respiratory quinone. The polar lipids consisted of phosphatidylcholine, phosphatidylethanolamine, one unidentified aminolipid and three unidentified lipids. Based on 16S rRNA gene sequence similarities, the type strains of Cyclobacterium amurskyense, Cyclobacterium marinum and Cyclobacterium lianum were most closely related to M12-11B(T) with sequence similarities of 98.2, 96.8 and 93.3 %, respectively. Other members of the family Cyclobacteriaceae had sequence similarities of <92.0 %. However, DNA-DNA hybridization with Cyclobacterium amurskyense KCTC 12363(T) and Cyclobacterium marinum DSM 745(T) showed relatedness values of only 24.5 and 32.5 % with respect to strain M12-11B(T). Based on the results of DNA-DNA hybridization experiments and phenotypic and chemotaxonomic data, it appears that strain M12-11B(T) represents a novel species of the genus Cyclobacterium, for which the name Cyclobacterium qasimii sp. nov. is proposed; the type strain is M12-11B(T) (= KCTC 23011(T) = NBRC 106168(T)) and it has a DNA G+C content of 40.5 mol%. PMID- 22039005 TI - Microbacterium amylolyticum sp. nov., isolated from soil from an industrial waste site. AB - A Gram-staining-positive, heterotrophic, aerobic, non-motile, non-endospore forming, yellow-coloured rod, designated strain N5(T), was isolated from a soil sample collected at an industrial waste site in Noida, on the outskirts of Delhi, India. In phylogenetic analyses based on 16S rRNA gene sequences, strain N5(T) was most closely related to members of established species in the genus Microbacterium (with sequence similarities of approximately 94.0-97.6 %), particularly Microbacterium indicum LMG 23459(T) (97.59 %) and Microbacterium gubbeenense LMG 19263(T) (97.18 %). In DNA-DNA hybridization studies, however, none of the DNA-DNA relatedness values between strain N5(T) and members of the genus Microbacterium exceeded 11.3 %. The genomic DNA G+C content of the novel strain was 68 mol%. The chemotaxonomic characteristics of strain N5(T), which had MK-11 and MK-10 as its major menaquinones and anteiso-C(15 : 0) (45 %), anteiso C(17 : 0) (37 %), iso-C(16 : 0) (8.5 %) and C(16 : 0) (4.5 %) as its predominant fatty acids, were consistent with classification in the genus Microbacterium. Peptidoglycan in the novel strain, which contained ornithine, alanine, glycine, homoserine, glutamic acid, 3-hydroxyglutamic acid, muramic acid and traces of N glycolyl residues, was of type B2beta. The polar lipid profile of strain N5(T) comprised diphosphatidylglycerol, phosphatidylglycerol and an unknown glycolipid. The novel strain's major cell-wall sugars were glucose and galactose. Based on the phylogenetic, DNA-DNA hybridization, chemotaxonomic and phenotypic data, strain N5(T) represents a novel species within the genus Microbacterium for which the name Microbacterium amylolyticum sp. nov. is proposed; the type strain is N5(T) (= DSM 24221(T) = CCM 7881(T)). PMID- 22039006 TI - Salisediminibacterium halotolerans gen. nov., sp. nov., a halophilic bacterium from soda lake sediment. AB - An orange-pigmented, Gram-reaction-positive, non-spore-forming, halophilic, alkali-tolerant rod, designated strain halo-2(T), was isolated from sediment of Xiarinaoer soda lake, in China's Inner Mongolia Autonomous Region. Strain halo 2(T) grew in a complex medium with 3-30 % (w/v) NaCl and at pH 5-10. The cell wall peptidoglycan contained meso-diaminopimelic acid and the major respiratory isoprenoid quinone was MK-7. The predominant cellular fatty acids were anteiso C(15 : 0) (43.6 %), anteiso-C(17 : 0) (14.8 %) and iso-C(15 : 0) (6.8 %) and the polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The genomic DNA G+C content of the novel strain was 48.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain halo-2(T) was most closely related to Bacillus agaradhaerens DSM 8721(T) (93.9 % sequence similarity). However, strain halo-2(T) could be clearly differentiated from its closest phylogenetic relatives on the basis of several phenotypic, genotypic and chemotaxonomic characteristics. Strain halo-2(T) therefore represents a novel species in a new genus for which the name Salisediminibacterium halotolerans gen. nov., sp. nov. is proposed. The type strain of the type species is halo-2(T) (= CGMCC 1.7654(T) = NBRC 104935(T)). PMID- 22039007 TI - Evolution and ecology meet molecular genetics: adaptive phenotypic plasticity in two isolated Negev desert populations of Acacia raddiana at either end of a rainfall gradient. AB - BACKGROUND AND AIMS: The ecological, evolutionary and genetic bases of population differentiation in a variable environment are often related to the selection pressures that plants experience. We compared differences in several growth- and defence-related traits in two isolated populations of Acacia raddiana trees from sites at either end of an extreme environmental gradient in the Negev desert. METHODS: We used random amplified polymorphic DNA (RAPD) to determine the molecular differences between populations. We grew plants under two levels of water, three levels of nutrients and three levels of herbivory to test for phenotypic plasticity and adaptive phenotypic plasticity. KEY RESULTS: The RAPD analyses showed that these populations are highly genetically differentiated. Phenotypic plasticity in various morphological traits in A. raddiana was related to patterns of population genetic differentiation between the two study sites. Although we did not test for maternal effects in these long-lived trees, significant genotype * environment (G * E) interactions in some of these traits indicated that such plasticity may be adaptive. CONCLUSIONS: The main selection pressure in this desert environment, perhaps unsurprisingly, is water. Increased water availability resulted in greater growth in the southern population, which normally receives far less rain than the northern population. Even under the conditions that we defined as low water and/or nutrients, the performance of the seedlings from the southern population was significantly better, perhaps reflecting selection for these traits. Consistent with previous studies of this genus, there was no evidence of trade-offs between physical and chemical defences and plant growth parameters in this study. Rather, there appeared to be positive correlations between plant size and defence parameters. The great variation in several traits in both populations may result in a diverse potential for responding to selection pressures in different environments. PMID- 22039008 TI - Inferences of biogeographical histories within subfamily Hyacinthoideae using S DIVA and Bayesian binary MCMC analysis implemented in RASP (Reconstruct Ancestral State in Phylogenies). AB - BACKGROUND AND AIMS: Subfamily Hyacinthoideae (Hyacinthaceae) comprises more than 400 species. Members are distributed in sub-Saharan Africa, Madagascar, India, eastern Asia, the Mediterranean region and Eurasia. Hyacinthoideae, like many other plant lineages, show disjunct distribution patterns. The aim of this study was to reconstruct the biogeographical history of Hyacinthoideae based on phylogenetic analyses, to find the possible ancestral range of Hyacinthoideae and to identify factors responsible for the current disjunct distribution pattern. METHODS: Parsimony and Bayesian approaches were applied to obtain phylogenetic trees, based on sequences of the trnL-F region. Biogeographical inferences were obtained by applying statistical dispersal-vicariance analysis (S-DIVA) and Bayesian binary MCMC (BBM) analysis implemented in RASP (Reconstruct Ancestral State in Phylogenies). KEY RESULTS: S-DIVA and BBM analyses suggest that the Hyacinthoideae clade seem to have originated in sub-Saharan Africa. Dispersal and vicariance played vital roles in creating the disjunct distribution pattern. Results also suggest an early dispersal to the Mediterranean region, and thus the northward route (from sub-Saharan Africa to Mediterranean) of dispersal is plausible for members of subfamily Hyacinthoideae. CONCLUSIONS: Biogeographical analyses reveal that subfamily Hyacinthoideae has originated in sub-Saharan Africa. S-DIVA indicates an early dispersal event to the Mediterranean region followed by a vicariance event, which resulted in Hyacintheae and Massonieae tribes. By contrast, BBM analysis favours dispersal to the Mediterranean region, eastern Asia and Europe. Biogeographical analysis suggests that sub-Saharan Africa and the Mediterranean region have played vital roles as centres of diversification and radiation within subfamily Hyacinthoideae. In this bimodal distribution pattern, sub-Saharan Africa is the primary centre of diversity and the Mediterranean region is the secondary centre of diversity. Sub-Saharan Africa was the source area for radiation toward Madagascar, the Mediterranean region and India. Radiations occurred from the Mediterranean region to eastern Asia, Europe, western Asia and India. PMID- 22039009 TI - Within sight of a rational pipeline for development of protein diagnostics. PMID- 22039010 TI - Troponin release--reversible or irreversible injury? Should we care? PMID- 22039011 TI - Rapid assessment of microbiological purity of dialysis water: the promise of solid-phase cytometry assessment and the epifluorescence microscopy method. PMID- 22039012 TI - The connections between vascular calcification and bone health. AB - Vascular calcification, bone loss and increased fracture risk are age-associated disorders. Several epidemiological studies have suggested a relationship between vascular calcification, impaired bone metabolism and increased mortality. So far, this relationship had been under-estimated as osteoporosis and vascular calcification have been considered non-modifiable disorders of aging. Recent data suggest that this association is not simply an artefact of age, stressing that the co-incidence of vascular calcification with low bone activity and osteoporosis could be biologically linked. During the development of vascular calcification, the transition of vascular smooth muscle cells towards an osteoblast-like phenotype promotes the release of the vesicular structures and mineralization within these structures is promoted by several players, including those related to mineral metabolism, like phosphorus, calcium or parathyroid hormone, which influence either the supersaturation within the structure or the expression of osteogenic factors. However, an intriguing question is whether the presence of vascular calcification impacts bone metabolism, thus demonstrating true crosstalk between these tissues. Evidence is now emerging, suggesting that some inhibitors of the Wnt pathway, such as secreted frizzled Proteins 2 and 4 and Dickkopf related protein-1 (DKK-1), may play a role linking vascular calcification and bone loss. An additional important question to answer, from the patient's perspective, is whether or not progression of vascular calcification can be prevented or restricted and whether altering this progression we can efficiently impact patients' outcomes. Much evidence suggests that the control of the chronic kidney disease-mineral and bone disorder components, particularly serum phosphorus, are the main targets to maintain normal bone turnover and protect against vascular calcification. PMID- 22039013 TI - Variation in parathyroid hormone immunoassay results--a critical governance issue in the management of chronic kidney disease. AB - Renal physicians strive to maintain parathyroid hormone (PTH) concentrations for patients with chronic kidney disease (CKD) within guideline limits, but poor method comparability means there is currently serious risk of clinical misclassification. The potential for under- or over-treatment is significant, representing a major challenge to patient safety. In the short-term, raising awareness of clinical implications of method-related differences in PTH is essential. Agreeing and adopting assay-specific PTH action limits for CKD patients as an interim measure is highly desirable and has been achieved in Scotland. Establishing pre-analytical requirements for PTH is also a priority. In the longer term, re-standardization of PTH methods in terms of an appropriate International Standard is required. Provided commutability can be demonstrated, the recently established IS 95/646 for PTH (1-84) is a suitable candidate. Establishment of a well-characterized panel of samples of defined clinical provenance to enable manufacturers to determine appropriate reference intervals and clinical decision points is also recommended and will provide an invaluable clinical resource. Recent developments in mass spectrometry mean that a candidate reference measurement procedure for PTH is now achievable and will represent major progress. Concurrently, evidence-based recommendations on clinical requirements and performance goals for PTH are required. Improving the comparability of PTH results requires support from many stakeholders but is achievable. PMID- 22039014 TI - Coenzyme A contained in mothers' milk is associated with the potential to induce atopic dermatitis. AB - T(h)2 adjuvant activity can be qualitatively and quantitatively evaluated using a mixed lymphocyte reaction and by changes in the intracellular cyclic adenosine 3',5'-monophosphate concentration, using human dendritic cells in vitro. The current study shows that mothers, whose children (n = 55) developed atopic dermatitis (AD) within 6 months after birth, often demonstrate a higher T(h)2 adjuvant activity in their milk, in comparison to those whose children did not develop such symptoms. Such an activity was recovered in a liquid phase of mothers' milk and was eluted as a single fraction by reversed-phase HPLC. Further analysis of this fraction by mass spectrometry showed that signals originating from a factor with a molecular weight of 767.53 are observed, exclusively in milk with a high T(h)2 adjuvant activity. The mass is exactly that of Coenzyme A (CoA), and indeed, a low concentration of CoA exhibited T(h)2 adjuvant activity both in vitro and in vivo. Moreover, mesenteric lymph node non-T cells obtained from mice that were orally treated with CoA led allogeneic naive CD4(+) T cells to differentiate into T(h)2. Furthermore, the oral administration of CoA induced rough skin, hyperplasia of the epidermis, hypergranulosis in the spinous layer and the thickening of the stratum in mice. These data collectively indicate that some of the patients with AD were exposed to mothers' milk carrying high T(h)2 adjuvant activity right after birth, which may be attributable to presence of CoA contained in the milk. PMID- 22039015 TI - Requirement of GATA-binding protein 3 for II13 gene expression in IL-18 stimulated Th1 cells. AB - Recent reports have revealed that CD4(+) T(h) cell subsets have the ability to alter their gene expression pattern in response to extracellular stimuli. We previously highlighted the plasticity of T(h)1 cells by demonstrating that T(h)1 cells gain the capacity to produce IL-3, IL-9, IL-13 and granulocyte macrophage colony-stimulating factor in response to antigen, IL-2 and IL-18, and based on their unique function, we designated these activated T(h)1 cells as 'super T(h)1 cells'. However, the precise molecular mechanism underlying IL-13 production by super T(h)1 cells has not been elucidated. Here, we show that the GATA-binding protein 3 (Gata3) is essentially required for II13 gene expression in super T(h)1 cells. Gata3 is synergistically induced in T-box expressed in T-cells (T-bet) expressing T(h)1 cells when co-stimulated with anti-CD3, IL-18 and IL-4 through the activation of nuclear factor of activated T cells, nuclear factor kappa-light chain-enhancer of activated B cells and signal transducer and activator of transcription 6, respectively. However, Gata3 induction is not satisfactory, and additional TCR or anti-CD3 signaling is prerequisite for triggering IL-13 production by Gata3 plus T-bet-expressing T(h)1 cells. These findings suggest that Gata3, which is not originally expressed in T(h)1 cells, alters the cytokine production profile by T(h)1 cells. PMID- 22039016 TI - IL-17/IFN-gamma double producing CD8+ T (Tc17/IFN-gamma) cells: a novel cytotoxic T-cell subset converted from Tc17 cells by IL-12. AB - It has been reported that IFN-gamma-producing CD8(+) T (Tc1) cells express cytotoxic molecules such as perforin and granzyme B to exhibit higher cytotoxicity against tumor cells compared with Tc2 cells. However, the critical role of IL-17-producing CD8(+) T (Tc17)-cell subsets in tumor immunity remains unclear. Tc17 cells differentiated from naive CD8(+) T cells did not possess cytotoxic molecules and exhibited no strong cytotoxicity. However, when Tc17 effector cells were further cultured with IL-12, they converted into IFN-gamma producing Tc17 cells, which mainly consisted of IL-17/IFN-gamma double-producing cells (Tc17/IFN-gamma). IL-12-converted Tc17 cells also acquired cytotoxic function in addition to IFN-gamma producibility. Moreover, they showed strong anti-tumor activity both in vitro and in vivo as well as Tc1 cells. Among four distinct subsets in IL-12-converted Tc17 cell populations, the isolated Tc17/IFN gamma cells exhibited cytotoxicity as well as IFN-gamma-producing Tc1-like cells. Thus, we first indicate direct evidence that Tc17/IFN-gamma cells, which were plastically converted from non-cytotoxic Tc17 cells by IL-12, exhibited strong anti-tumor activity as well as Tc17 cell-derived Tc1-like cells. PMID- 22039017 TI - Systematic analysis of factors related to display of the twinkling artifact by a phantom: an optimized investigation. AB - OBJECTIVES: The purpose of this study was to analyze factors related to display of the twinkling artifact by a phantom. METHODS: An in vitro phantom made of sandpaper was designed to mimic rough physiologic surfaces prone to generating the twinkling artifact. Sandpaper strips embedded in a plastic box were scanned through a water path under different machine settings with only 1 parameter varied each time. After choosing the best settings for displaying the twinkling artifact, 4 types of sandpaper with different roughness were scanned. The resulting images were recorded at random, and the number of color pixels in the color box of each image was calculated by a custom-designed program developed using commercially available software. All data were then evaluated by regression analysis, a paired 2-tailed Student t test, and single-factor analysis of variance. RESULTS: The highest color write priority and color gain, which were just below the threshold for color noise, a focus depth setting below the sandpaper, a maximum wall filter under a higher pulse repetition frequency, and a color box adjusted properly in the fundamental imaging mode (P < .001) were found to most readily improve the twinkling artifact intensity. The roughness of the sandpaper was shown to be highly correlated with the twinkling artifact intensity (R(2) = 0.832; P < .001). CONCLUSIONS: The twinkling artifact was influenced by some machine parameters and the roughness of the sandpaper. By adjusting some ultrasound machine parameters, a better image reflecting the twinkling artifact can be shown in clinical practice and research. PMID- 22039018 TI - Real-time video streaming of sonographic clips using domestic internet networks and free videoconferencing software. AB - OBJECTIVES: As the use of point-of-care sonography spreads, so too does the need for remote expert over-reading via telesonogrpahy. We sought to assess the feasibility of using familiar, widespread, and cost-effective existent technology to allow remote over-reading of sonograms in real time and to compare 4 different methods of transmission and communication for both the feasibility of transmission and image quality. METHODS: Sonographic video clips were transmitted using 2 different connections (WiFi and 3G) and via 2 different videoconferencing modalities (iChat [Apple Inc, Cupertino, CA] and Skype [Skype Software Sarl, Luxembourg]), for a total of 4 different permutations. The clips were received at a remote location and recorded and then scored by expert reviewers for image quality, resolution, and detail. RESULTS: Wireless transmission of sonographic clips was feasible in all cases when WiFi was used and when Skype was used over a 3G connection. Images transmitted via a WiFi connection were statistically superior to those transmitted via 3G in all parameters of quality (average P = .031), and those sent by iChat were superior to those sent by Skype but not statistically so (average P = .057). CONCLUSIONS: Wireless transmission of sonographic video clips using inexpensive hardware, free videoconferencing software, and domestic Internet networks is feasible with retention of image quality sufficient for interpretation. WiFi transmission results in greater image quality than transmission by a 3G network. PMID- 22039019 TI - Assessment of glottic squamous cell carcinoma: comparison of sonography and non contrast-enhanced magnetic resonance imaging. AB - OBJECTIVES: The purpose of this study was to compare the use of sonography and non-contrast-enhanced magnetic resonance imaging (MRI) for detection and staging of glottic carcinoma. METHODS: In this study, 30 consecutive patients with glottic squamous cell carcinoma underwent high-frequency sonography and non contrast-enhanced MRI before surgical treatment. Tumor detectability and imaging findings were evaluated independently and then compared with the surgical and postoperative pathologic findings. RESULTS: Sonography showed a trend toward higher detectability than MRI in early (stage T1 and T2) glottic carcinoma (94.1% [16 of 17 patients] for sonography versus 76.5% [13 of 17 patients] for MRI; P = .335). With regard to T staging, the overall accuracy rates were 80.0% (24 of 30) for sonography and 76.7% (23 of 30) for MRI; the difference was not statistically significant (P > .99). Non-contrast-enhanced MRI was superior to sonography in showing tumor involvement in the retrolaryngeal extent of glottic carcinoma. CONCLUSIONS: Sonography is suggested as a noninvasive complementary modality for detection and initial staging of glottic carcinoma. PMID- 22039020 TI - Sonographically guided transthoracic biopsy of peripheral lung and mediastinal lesions: role of contrast-enhanced sonography. AB - OBJECTIVES: The purpose of this study was to assess the impact of contrast enhanced sonography on sonographically guided transthoracic needle biopsy of lung lesions. METHODS: A total of 121 patients underwent sonographically guided transthoracic needle cutting biopsy. Of the 121 patients, 62 (contrast-enhanced sonography group) underwent contrast-enhanced sonography before biopsy, and the information from contrast-enhanced sonography was used to optimize the biopsy procedure. The remaining 59 patients constituted the non-contrast-enhanced sonography group. The enhancement patterns and echogenicity were evaluated by the consensus of 2 sonographers. The diagnostic efficacy was compared between the contrast-enhanced and non-contrast-enhanced sonography groups. RESULTS: The enhancement intensity and extent varied greatly among different thoracic lesions, and an anechoic area (necrosis) was revealed in 26 of 62 lesions (41.9%) lesions after administration of the contrast agent. The overall diagnostic accuracy of sonographically guided transthoracic biopsy in this study was 85.9% (104 of 121). In the contrast-enhanced sonography group, the initial biopsy led to correct diagnosis in 58 of 62 lesions (93.6%). In the non-contrast-enhanced sonography group, the initial biopsy led to correct diagnosis in 46 of 59 lesions (78.0%). The difference in the diagnostic accuracy between the contrast-enhanced and non contrast-enhanced sonography groups was statistically significant (P < .05). CONCLUSIONS: Contrast-enhanced sonography enables differentiation of viable from necrotic portions of thoracic lesions and has a positive impact on the diagnostic efficacy of sonographically guided transthoracic needle biopsy. PMID- 22039021 TI - Occurrence and value of the color Doppler "line sign" after radiofrequency ablation of solid abdominal organs. AB - OBJECTIVES: The purposes of this study were to identify the frequency of the color "line sign" after track coagulation during electrode removal and to evaluate the usefulness of color Doppler sonography in predicting complications after radiofrequency ablation. METHODS: A total of 104 consecution radiofrequency ablations of either the liver (n = 68) or the kidney (n = 36) were evaluated for hemorrhagic complications by color Doppler sonography. All radiofrequency ablations were performed in a similar fashion, including track coagulation during electrode removal. Follow-up computed tomography of the organ of interest was performed within 24-hours after the procedure. RESULTS: The study included 32 patients with 36 renal radiofrequency ablations and 43 patients with 68 hepatic ablations. There were 1 arterial and 0 venous Doppler signals in the renal ablations and 2 arterial and 2 venous Doppler signals in the hepatic ablations. No major complications were observed, but a moderate hematoma occurred in 1 renal ablation. A statistically significant correlation was noted between the computed tomographic findings of hematomas and the presence of a color line sign (P = .048). We found a lower percentage of the color line sign compared to prior reports that identified this sign after biopsy of the liver or kidney. CONCLUSIONS: There is a decreased frequency of the color line sign and hemorrhagic complications after radiofrequency ablation compared to their rates of occurrence with core biopsy. Identification of the color line sign may be useful for predicting hemorrhagic complications. PMID- 22039022 TI - Differentiating malignant from benign thickening of the gallbladder wall by the use of acoustic radiation force impulse elastography. AB - OBJECTIVES: The purpose of this study was to determine whether real-time elastography can differentiate gallbladder carcinoma from benign gallbladder wall thickening. METHODS: Sonographic and real-time elastographic examinations were done in 125 of 2000 consecutive patients who had an increased gallbladder wall thickness of more than 3 mm. Shear wave velocities were determined for a normal gallbladder wall, a benign thickened gallbladder wall, and gallbladder carcinoma, and a value of 2.7 m/s was set as the cutoff to differentiate between benign and malignant wall thickening. Virtual touch and color maps of the gallbladder wall were also obtained. The final diagnosis was confirmed by histopathologic examination of the resected gallbladder or by guided fine-needle aspiration cytologic examination. Statistical analysis was done to determine the sensitivity and specificity of elastography for gallbladder carcinoma and benign wall thickening. Student t test and area under the receiver operating characteristic curve analyses were done to determine the statistical significance of the results. RESULTS: Elastography had sensitivity and specificity of 100% and 91.3%, respectively, for diagnosing gallbladder carcinoma with a mean shear wave velocity of 3.41 m/s (P < .0001) and an area under the curve of 0.92. False positive findings of acute cholecystitis occurred in 8.5% of cases, which also had an increased shear wave velocity of greater than 2.7 m/s. The overall accuracy of elastography for differentiating gallbladder carcinoma from benign wall thickening was 92.8%. CONCLUSIONS: Elastography is an accurate technique for differentiating between benign and malignant gallbladder wall thickening and can be combined with sonography as the prime imaging tool for diagnosing gallbladder carcinoma at an early stage. PMID- 22039023 TI - Accuracy of sonographically guided and palpation guided scaphotrapeziotrapezoid joint injections. AB - OBJECTIVES: The purpose of this study was to determine and compare the accuracies of sonographically guided and palpation guided scaphotrapeziotrapezoid (STT) joint injections in a cadaveric model. METHODS: A clinician with 6 years of experience performing sonographically guided procedures injected 1.0 mL of a diluted latex solution into the STT joints of 20 unembalmed cadaveric wrist specimens using a palmar approach. At a minimum of 24 hours after injection, an experienced clinician specializing in hand care completed palpation guided injections in the same specimens using a dorsal approach and 1 mL of a different colored latex. A fellowship-trained hand surgeon blinded to the injection technique then dissected each specimen to assess injection accuracy. Injections were graded as accurate if the colored latex was found in the STT joint, whereas inaccurate injections resulted in no latex being found in the joint. RESULTS: All sonographically guided injections were accurate (100%; 95% confidence interval, 81%-100%), whereas only 80% of palpation guided injections were accurate (95% confidence interval, 61%-99%). Sonographically guided injections were significantly more accurate than palpation guided injections, as determined by the ability to deliver latex into the joint (P < .05). CONCLUSIONS: Sonographic guidance can be used to inject the STT joint with a high degree of accuracy and is more accurate than palpation guidance within the limits of this study design. Clinicians should consider using sonographic guidance to perform STT joint injections when precise intra-articular placement is desired. Further clinical investigation examining the role of sonographically guided STT joint injections in the treatment of patients with radial wrist pain syndromes is warranted. PMID- 22039024 TI - Imaging of endometrial carcinoma using contrast-enhanced sonography. AB - OBJECTIVES: The purpose of this study was to evaluate the utility of contrast enhanced sonography as an adjunct to conventional transvaginal sonography for detecting endometrial carcinoma and defining the depth of myometrial invasion. METHODS: A total of 35 patients with endometrial carcinoma diagnosed by endometrial sampling were examined with transvaginal sonography followed by contrast-enhanced sonography before treatment. The contrast enhancement phases (ie, early wash-in/out and late wash-in/out) were visually observed before comparison of tumors grouped by average diameter and histopathologic grade. We evaluated the effectiveness of contrast-enhanced sonography as an adjunct to transvaginal sonography in tumor imaging. We calculated the accuracy of contrast enhanced sonography for diagnosing the depth of tumor invasion into the myometrium by using arcuate vascular plexus involvement as the sonographic standard for diagnosis of deep myometrial infiltration. RESULTS: Of the 34 tumors identified by contrast-enhanced sonography, 28 (82.4%) showed early wash-in, and 6 (17.6%) showed late wash-in. Similar numbers of cases showed early and late wash-out. The enhancement phases did not differ significantly across groups with different average tumor diameters or histologic grades (P > .05). Contrast enhanced sonography contributed the most to tumor imaging in patients with a thin endometrium after endometrial biopsy because it enhanced the contrast between the tumor and tissue. The diagnostic accuracy of contrast-enhanced sonography for determining the myometrium infiltration depth was 85.3%. CONCLUSIONS: This study revealed diagnostically useful characteristics of the enhancement phase of endometrial carcinoma. The ability to enhance tumor-to-tissue contrast makes contrast-enhanced sonography a valuable adjunct to conventional sonography of endometrial carcinoma, especially for the thin endometrium found after endometrial biopsy. Contrast-enhanced sonography performed well in the diagnosis of the myometrial infiltration depth when using arcuate vascular plexus involvement as a marker of deep myometrial infiltration. PMID- 22039025 TI - Bowel circulation in normally grown and growth-restricted fetuses. AB - OBJECTIVES: The purpose of this study was to characterize bowel blood flow and its relationship with cerebral and placental circulations in normally grown and growth-restricted fetuses. METHODS: In a cross-sectional prospective study of singleton normally grown fetuses, Doppler blood flow pulsatility indices were measured in the superior mesenteric artery, middle cerebral artery, and umbilical artery from 19 to 38 weeks' gestation. The same Doppler parameters were examined in intrauterine growth-restricted (IUGR) fetuses and analyzed as two groups: (1) without a brain-sparing effect, defined as an umbilical artery/middle cerebral artery ratio of less than 1; and (2) with a brain-sparing effect, defined as an umbilical artery/middle cerebral artery ratio of greater than 1. RESULTS: A total of 262 appropriate-for-gestational-age fetuses were analyzed for superior mesenteric artery Doppler pulsatility index values; 196 were simultaneously examined for umbilical artery and middle cerebral artery pulsatility index values. Forty-three IUGR fetuses were similarly analyzed. In appropriate-for gestational-age fetuses, both the bowel and brain circulations showed a globally higher pulsatility index as pregnancy advanced, resulting in an almost constant middle cerebral artery/superior mesenteric artery ratio (r(2) = 0.079). The IUGR fetuses had a lower superior mesenteric artery pulsatility index compared to the appropriate-for-gestational-age fetuses, which was more pronounced in those with brain sparing (group 2) than in group 1 (Z = -0.97 and -0.53, respectively; P < .0001). The middle cerebral artery/superior mesenteric artery ratio was higher with respect to the appropriate-for-gestational-age fetuses in group 1, whereas the ratio in group 2 was lower (Z = 0.16 and -0.60). CONCLUSIONS: We have shown the existence of a superior mesenteric artery sparing effect in IUGR fetuses. This reaction seems to correlate positively with the severity of the growth restriction. PMID- 22039026 TI - Assessment of lung volume by 3-dimensional sonography and magnetic resonance imaging in fetuses with congenital diaphragmatic hernias. AB - OBJECTIVES: The purpose of this study was to evaluate the influence of different rotation angles in assessment of the contralateral lung volume by 3-dimensional (3D) sonography in comparison to magnetic resonance imaging (MRI) in fetuses with congenital diaphragmatic hernias. METHODS: A total of 126 measurements by 3D sonography and MRI were conducted in 81 patients between 18 and 39 weeks' gestation. The 3D sonographic volumes of the contralateral fetal lung were calculated by the rotational technique (virtual organ computer-aided analysis) with rotation angles of 6 degrees , 15 degrees , and 30 degrees . Transverse multiplanar T2-weighted MRI was performed for the MRI measurements. To compare the accuracy of 3D sonographic volumetry using different rotation angles, MRI assessment was taken as the reference method, and percentage errors and limits of agreement were calculated for each angle. RESULTS: Three-dimensional sonographic volume measurements showed a high correlation with MRI (6 degrees angle, R(2) = 0.86; 15 degrees angle, R(2) = 0.78; 30 degrees angle, R(2) = 0.68). The mean percentage error showed no systematic error. With regard to random error, the 6 degrees step had significantly lower values than the larger angles 30 degrees step (R = 0.472) and the narrowest limits of agreement. CONCLUSIONS: Especially when using a small rotation angle, assessment of the contralateral fetal lung volume by 3D sonography in congenital diaphragmatic hernias is a reliable alternative to MRI. PMID- 22039027 TI - Outcomes of fetuses with umbilical cord cysts diagnosed during nuchal translucency examination. AB - OBJECTIVES: The purpose of this study was to report the outcomes of fetuses with the finding of an umbilical cord cyst during nuchal translucency examination in a low-risk population. METHODS: A retrospective study was conducted in a large tertiary referral academic center over a 3-year period. All fetuses with umbilical cord cysts during the nuchal translucency scan were recruited, and their medical data concerning the pregnancy and neonatal course were analyzed. RESULTS: Eight fetuses (0.7%) had a diagnosis of an umbilical cord cyst among the 1080 nuchal translucency examinations. The mean cyst diameter was 19 mm (range, 10-38 mm). The male to female ratio was 6:2. Isolated umbilical cord cysts were found in 5 cases (62.5%), and in all, the nuchal translucency measured less than 2 mm; the cysts resolved; and the outcomes were normal. Three fetuses (37.5%) had additional associated malformations. In all of them, the cysts persisted during pregnancy. Two of them had increased nuchal translucency (3.2 and 4.2 mm). In these 2 cases, 1 fetus had a hypoplastic left heart with a normal karyotype, and the other had multiple malformations and trisomy18. Both pregnancies were terminated. The third case, with normal nuchal translucency, had an ectopic kidney and a patent urachus, which closed spontaneously at 23 weeks and resulted in a normal pregnancy outcome. CONCLUSIONS: A favorable outcome is expected when an umbilical cord cyst diagnosed during late first trimester presents as an isolated finding associated with normal nuchal translucency and resolves later on. PMID- 22039028 TI - Value of "minimum menstrual age" in determining early pregnancy failure. AB - OBJECTIVES: The purposes of this study were to assess a discriminatory "minimum menstrual age" (28 days + number of days elapsed between the first positive pregnancy test result and sonogram) for the diagnosis of early pregnancy failure when no embryonic/fetal heartbeat is seen and to compare minimum menstrual age dating with last menstrual period and sonographic dating. METHODS: We conducted a retrospective study of 338 initial first-trimester sonographic examinations among women with suspected early pregnancy failure. A minimum menstrual age for each was calculated, and pregnancy outcomes were assessed. The predictive value of the minimum menstrual age for the pregnancy outcome was assessed at both 42 and 49 days and compared to that of dating by the last menstrual period and sonography. RESULTS: Among a study cohort of 338 patients, the average gestational age calculated by the last menstrual period was 53 days; by sonography, it was 50 days; and by the minimum menstrual age, it was 35 days (P < .01). All cases in which there was no sonographically detectable embryonic heartbeat above a minimum menstrual age of 42 days resulted in pregnancy failure. CONCLUSIONS: The minimum menstrual age is a conservative estimate of the gestational age, with an estimated positive predictive value of 100% for early pregnancy failure when no embryonic heartbeat is seen after 42 days. The minimum menstrual age can be combined with other existing diagnostic clues to predict early pregnancy failure with greater accuracy. PMID- 22039029 TI - Perinatal outcomes in twin pregnancies with discordant Doppler velocimetric findings. AB - OBJECTIVES: The purpose of this study was to investigate whether poor perinatal outcomes are more common in twins with abnormal umbilical artery Doppler velocimetric findings than in their siblings with normal findings. METHODS: A matched-pair cohort analysis of twin pregnancies with discordant umbilical artery Doppler velocimetric findings (one normal and one abnormal) was performed. Both severely abnormal findings (defined as absent or reversed flow in one twin; n = 23) and mildly abnormal findings (defined as an elevated systolic to diastolic ratio in one twin; n = 28) were included. The matched twins provided a gestational age-and demographically matched comparison group. Outcomes measured included intrauterine fetal death, oligohydramnios, intrauterine growth restriction, and neonatal outcomes (birth weight, Apgar scores, intraventricular hemorrhage, necrotizing enterocolitis, respiratory distress syndrome, bronchopulmonary dysplasia, and sepsis). Associations between abnormal Doppler velocimetric findings and perinatal outcomes were estimated using matched logistic regression analysis. RESULTS: Among this cohort of twin pregnancies with discordant umbilical artery Doppler velocimetric findings, oligohydramnios and intrauterine growth restriction were more frequent in twin fetuses with abnormal findings. Adverse neonatal outcomes were high in both groups (57% among those with normal findings and 49% among those with abnormal findings) because of the overwhelming contribution of preterm delivery (mean gestational age at delivery, 33.3 weeks) but were not significantly different between those fetuses with abnormal findings compared to their cotwins with normal findings. CONCLUSIONS: Our results do not show an association between abnormal umbilical artery Doppler velocimetric findings and short-term adverse neonatal outcomes. PMID- 22039030 TI - Importance of renal abnormalities first identified in the third trimester after normal findings on a detailed second-trimester structural fetal survey. AB - OBJECTIVES: The purpose of this study was to evaluate the importance of renal abnormalities first identified in the third trimester of pregnancy after normal findings on a detailed second-trimester structural fetal survey. METHODS: Between March 1, 2007, and August 1, 2009, all patients having a sonographic examination in the third trimester who previously had normal findings on a second-trimester detailed structural fetal survey were retrospectively identified. Fetal renal abnormalities first detected in the third trimester and not seen during the second-trimester survey were tabulated. Neonatal follow-up was obtained for those with sonographic abnormalities. RESULTS: Overall, 4170 patients had third trimester scans after normal findings on a detailed second-trimester survey. A new renal abnormality was detected in 77 (1.8%) of these third-trimester scans. Detailed postnatal imaging follow-up was available in 49 of 77 (63.6%), of which 44 (89.8%) had prenatal hydronephosis. Of these, 9 of 44 (20.5%) had reflux; 14 of 44 (31.8%) had normal findings or had hydronephosis that resolved on follow-up sonography after birth; and the rest had hydronephosis (13 of 44 [29.5%]), ureterovesical junction obstruction (3 of 44 [6.8%]), or ureteropelvic junction obstruction (5 of 44 [11.4%]). The other 5 fetuses with nonhydronephrotic renal abnormalities had pelvic kidneys (3) and unilateral renal agenesis (2). Two of those with reflux (22.2%) required surgery, and 1 of those with ureterovesical junction obstruction (33.3%) required surgery. CONCLUSIONS: Most renal abnormalities first identified in the third trimester after normal findings on a detailed second-trimester structural fetal survey were hydronephrosis, of which approximately one-third resolved after birth. Among the remaining neonates with persistent hydronephrosis, almost one-third had reflux that was not detected on the second-trimester anatomy scan. PMID- 22039031 TI - Amniotic fluid and the clinical relevance of the sonographically estimated amniotic fluid volume: oligohydramnios. AB - The amniotic fluid volume (AFV) is regulated by several systems, including the in tramembranous pathway, fetal production (fetal urine and lung fluid) and uptake (fetal swallowing), and the balance of fluid movement via osmotic gradients. The normal AFV across gestation has not been clearly defined; consequently, abnormal volumes are also poorly defined. Actual AFVs can be measured by dye dilution techniques and directly measured at cesarean delivery; however, these techniques are time-consuming, are invasive, and require laboratory support, and direct measurement can only be done at cesarean delivery. As a result of these limitations, the AFV is estimated by the amniotic fluid index (AFI), the single deepest pocket, and subjective assessment of the AFV. Unfortunately, sonographic estimates of the AFV correlate poorly with dye-determined or directly measured amniotic fluid. The recent use of color Doppler sonography has not improved the diagnostic accuracy of sonographic estimates of the AFV but instead has led to overdiagnosis of oligohydramnios. The relationship between the fixed cutoffs of an AFI of 5 cm or less and a single deepest pocket of 2 cm or less for identifying adverse pregnancy outcomes is uncertain. The use of the single deepest pocket compared to the AFI to identify oligohydramnios in at-risk pregnancies seems to be a better choice because the use of the AFI leads to an increase in the diagnosis of oligohydramnios, resulting in more labor inductions and cesarean deliveries without any improvement in peripartum outcomes. PMID- 22039032 TI - Sonographically guided distal radioulnar joint injection: technique and validation in a cadaveric model. AB - Distal radioulnar joint (DRUJ) disorders are uncommon but important causes of ulnar-sided wrist pain and disability. Fluoroscopically guided injections may be performed to diagnose or treat DRUJ-related pain or as part of a diagnostic arthrogram. Sonographic guidance may provide a favorable alternative to fluoroscopic guidance for distal DRUJ injections. This report describes and validates a sonographically guided technique for DRUJ injections in an unembalmed cadaveric model. An experienced clinician used sonographic guidance to inject diluted colored latex into the DRUJs of 10 unembalmed cadaveric specimens. Subsequent dissection by a fellowship-trained hand surgeon confirmed accurate injections in all 10 specimens. Two cases of ulnocarpal flow, indicative of triangular fibrocartilage injury, were noted during injection and subsequently confirmed during dissection. Clinicians should consider using sonographic guidance to perform DRUJ injections when clinically indicated. Further research should explore the efficacy of sonographically guided DRUJ injections to treat patients with painful DRUJ syndromes or to evaluate the triangular fibrocartilage complex in patients with ulnar wrist pain syndromes. PMID- 22039033 TI - Acoustic radiation force impulse elastography and contrast-enhanced sonography of sinusoidal obstructive syndrome (Veno-occlusive Disease): preliminary results. AB - We report quantitative liver acoustic radiation force impulse (ARFI) elastographic findings in 2 cases of sinusoidal obstructive syndrome and liver contrast-enhanced sonographic features in one of these cases. To our knowledge, findings in this condition from these techniques have not been reported previously. Acoustic radiation force impulse elastography showed median high shear wave velocities (case 1, 2.75 m/s; case 2, 2.58 m/s) that normalized after specific treatment for sinusoidal obstructive syndrome; therefore, ARFI elastography provided quantitative information that helped diagnose this condition as well as monitor the response to treatment. Contrast-enhanced sonographic findings in one of the cases showed patchy liver enhancement that correlated with the high-velocity patchy distribution on ARFI elastography in that case and enhanced multidetector row computed tomographic findings in the other case. This contrast-enhanced sonographic pattern progressively normalized during follow-up after specific treatment. The elastographic features in both cases and contrast-enhanced sonographic features in one of them contributed to early diagnosis and follow-up of sinusoidal obstructive syndrome in both patients. Further prospective studies are necessary to define the role of ARFI elastography and contrast-enhanced sonography in the early diagnosis and clinical follow-up of this condition. PMID- 22039034 TI - Isolated periportal tuberculosis causing portal vein thrombosis. PMID- 22039035 TI - Symptomatic complete vertebral carotid steal syndrome caused by innominate artery stenosis and an arteriovenous right forearm fistula. PMID- 22039036 TI - Extragonadal tumor and testicular microlithiasis: "burned-out" tumors are represented by macrocalcification. PMID- 22039037 TI - Molecular prognostic factors of anaplastic oligodendroglial tumors and its relationship: a single institutional review of 77 patients from China. AB - The increased chemosensitivity of oligodendroglial tumors has been associated with loss of heterozygosity (LOH) on chromosomes 1p and 19q. Other clinical and molecular factors have also been identified as being prognostic and predictive for treatment outcome. Seventy-seven patients with anaplastic oligodendroglioma (AO) or anaplastic oligoastrocytoma (AOA), treated in Beijing Tiantan Hospital from 2006 through 2008, were reviewed. LOH 1p, LOH 19q, IDH1 mutation, O(6) methylguanine-DNA methyltransferase (MGMT) promoter methylation, and protein expression level of MGMT, P53, EGFR, and Ki-67 were evaluated. Age at diagnosis, LOH 1p and 19q, IDH1 mutation, P53 expression level, reoperation when progression, and adjuvant chemotherapy were statistically significant factors for overall survival (OS) in univariate analysis. Further multivariate analysis showed that age at diagnosis (P = .010), LOH 1p and 19q (P = .016), IDH1 mutation (P = .011), and reoperation after progression (P = .048) were independent predictors for longer survival in these patients. Nonrandom associations were found between LOH 1p and LOH 19q, MGMT promoter methylation and LOH 1p or 19q, IDH1 mutation and LOH 1p and 19q, IDH1 mutation and MGMT promoter methylation, whereas mutual exclusion was found between MGMT promoter methylation and MGMT expression level. The present study confirmed that age at diagnosis, LOH 1p and 19q, IDH1 mutation, and reoperation after progression were independent significant prognostic factors for patients with anaplastic oligodendroglial tumors. Inter-relationship between LOH 1p, LOH 19q, IDH1 mutation, MGMT promoter methylation, and MGMT expression level were also revealed. Future clinical trials for AO and AOA should consider the molecular alterations of patients. PMID- 22039038 TI - Gastric bypass and duodenal and gastric feeding: a comment to Hansen et al. PMID- 22039040 TI - Seroprevalence of vectorborne diseases in free-roaming dogs in Goa, India. PMID- 22039041 TI - Patient based computational fluid dynamic characterization of carotid bifurcation stenosis before and after endovascular revascularization. AB - INTRODUCTION: Hemodynamic forces play a critical role in determining the molecular phenotype of the endothelial cell and in influencing vascular remodeling. A lesion based computational fluid dynamic (CFD) modeling approach is presented to understand the complex spatial and temporal hemodynamic changes that prevail in carotid stenosis (CS) in patients with critical CS undergoing carotid artery stenting (CAS). METHODS: High resolution three-dimensional rotational angiography volumetric datasets were acquired before and after treatment in eight patients, segmented and used to generate a high quality structured hexahedral computational mesh with boundary layer refinement. CFD analysis was carried out using a time dependent laminar flow model implementing non-Newtonian realistic blood viscosity for blood, and used to compute wall shear stress (WSS) and its gradient (WSSG). RESULTS: CAS restored fully or near laminar flow in all cases in our series. In addition, WSS was found to decrease in the stented region in all cases, reduced to near normal levels of 34+/-14 dyn/cm(2) with significant blunting of the extreme pretreatment WSSG to levels lower than 1000 dyn/cm(3). CONCLUSIONS: In this series of patients with symptomatic CS, CFD simulation enabled estimation of the hemodynamic effect of CAS, leading to reversal of abnormal flow patterns and wall shear forces around the arterial stenosis, with normalization of flow laminarity and wall shear spatiotempotal patterns known to be associated with adverse endothelial cell function. PMID- 22039042 TI - Diversity of release patterns for jail detainees: implications for public health interventions. AB - OBJECTIVES: We sought to develop a detailed description of the variety of jail release patterns and to learn what factors affect the length of stay (LOS). METHODS: The main data set for the study came from a biennial Bureau of Justice Statistics survey on felony defendants in large urban counties. RESULTS: The median LOS for the felony defendants was 7 days. One quarter of the jails had a median LOS of less than 2 days; median LOS for 75% of the jails was less than 15 days. Median regression showed that male gender, previous arrests, and violent charges were predictive of longer LOS. CONCLUSIONS: The diversity in release patterns among jails has not been previously described. A public health intervention feasible in one jail may not be feasible in another because of the heterogeneity of release patterns. Individual inmate characteristics could predict a slower rate of release. PMID- 22039043 TI - A renewed commitment to environmental justice in health disparities research. PMID- 22039044 TI - Structural determinants of ubiquitin-CXC chemokine receptor 4 interaction. AB - Ubiquitin, a post-translational protein modifier inside the cell, functions as a CXC chemokine receptor (CXCR) 4 agonist outside the cell. However, the structural determinants of the interaction between extracellular ubiquitin and CXCR4 remain unknown. Utilizing C-terminal truncated ubiquitin and ubiquitin mutants, in which surface residues that are known to interact with ubiquitin binding domains in interacting proteins are mutated (Phe-4, Leu-8, Ile-44, Asp-58, Val-70), we provide evidence that the ubiquitin-CXCR4 interaction follows a two-site binding mechanism in which the hydrophobic surfaces surrounding Phe-4 and Val-70 are important for receptor binding, whereas the flexible C terminus facilitates receptor activation. Based on these findings and the available crystal structures, we then modeled the ubiquitin-CXCR4 interface with the RosettaDock software followed by small manual adjustments, which were guided by charge complementarity and anticipation of a conformational switch of CXCR4 upon activation. This model suggests three residues of CXCR4 (Phe-29, Phe-189, Lys 271) as potential interaction sites. Binding studies with HEK293 cells overexpressing wild type and CXCR4 after site-directed mutagenesis confirm that these residues are important for ubiquitin binding but that they do not contribute to the binding of stromal cell-derived factor 1alpha. Our findings suggest that the structural determinants of the CXCR4 agonist activity of ubiquitin mimic the typical structure-function relationship of chemokines. Furthermore, we provide evidence for separate and specific ligand binding sites on CXCR4. As exogenous ubiquitin has been shown to possess therapeutic potential, our findings are expected to facilitate the structure-based design of new compounds with ubiquitin-mimetic actions on CXCR4. PMID- 22039045 TI - Enterolobium contortisiliquum trypsin inhibitor (EcTI), a plant proteinase inhibitor, decreases in vitro cell adhesion and invasion by inhibition of Src protein-focal adhesion kinase (FAK) signaling pathways. AB - Tumor cell invasion is vital for cancer progression and metastasis. Adhesion, migration, and degradation of the extracellular matrix are important events involved in the establishment of cancer cells at a new site, and therefore molecular targets are sought to inhibit such processes. The effect of a plant proteinase inhibitor, Enterolobium contortisiliquum trypsin inhibitor (EcTI), on the adhesion, migration, and invasion of gastric cancer cells was the focus of this study. EcTI showed no effect on the proliferation of gastric cancer cells or fibroblasts but inhibited the adhesion, migration, and cell invasion of gastric cancer cells; however, EcTI had no effect upon the adhesion of fibroblasts. EcTI was shown to decrease the expression and disrupt the cellular organization of molecules involved in the formation and maturation of invadopodia, such as integrin beta1, cortactin, neuronal Wiskott-Aldrich syndrome protein, membrane type 1 metalloprotease, and metalloproteinase-2. Moreover, gastric cancer cells treated with EcTI presented a significant decrease in intracellular phosphorylated Src and focal adhesion kinase, integrin-dependent cell signaling components. Together, these results indicate that EcTI inhibits the invasion of gastric cancer cells through alterations in integrin-dependent cell signaling pathways. PMID- 22039046 TI - Nitrogen-responsive regulation of GATA protein family activators Gln3 and Gat1 occurs by two distinct pathways, one inhibited by rapamycin and the other by methionine sulfoximine. AB - Nitrogen availability regulates the transcription of genes required to degrade non-preferentially utilized nitrogen sources by governing the localization and function of transcription activators, Gln3 and Gat1. TorC1 inhibitor, rapamycin (Rap), and glutamine synthetase inhibitor, methionine sulfoximine (Msx), elicit responses grossly similar to those of limiting nitrogen, implicating both glutamine synthesis and TorC1 in the regulation of Gln3 and Gat1. To better understand this regulation, we compared Msx- versus Rap-elicited Gln3 and Gat1 localization, their DNA binding, nitrogen catabolite repression-sensitive gene expression, and the TorC1 pathway phosphatase requirements for these responses. Using this information we queried whether Rap and Msx inhibit sequential steps in a single, linear cascade connecting glutamine availability to Gln3 and Gat1 control as currently accepted or alternatively inhibit steps in two distinct parallel pathways. We find that Rap most strongly elicits nuclear Gat1 localization and expression of genes whose transcription is most Gat1-dependent. Msx, on the other hand, elicits nuclear Gln3 but not Gat1 localization and expression of genes that are most Gln3-dependent. Importantly, Rap-elicited nuclear Gln3 localization is absolutely Sit4-dependent, but that elicited by Msx is not. PP2A, although not always required for nuclear GATA factor localization, is highly required for GATA factor binding to nitrogen-responsive promoters and subsequent transcription irrespective of the gene GATA factor specificities. Collectively, our data support the existence of two different nitrogen-responsive regulatory pathways, one inhibited by Msx and the other by rapamycin. PMID- 22039047 TI - Identification and mechanism of 10-carbon fatty acid as modulating ligand of peroxisome proliferator-activated receptors. AB - Peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) are a subfamily of nuclear receptors that plays key roles in glucose and lipid metabolism. PPARgamma is the molecular target of the thiazolidinedione class of antidiabetic drugs that has many side effects. PPARgamma is also activated by long chain unsaturated or oxidized/nitrated fatty acids, but its relationship with the medium chain fatty acids remains unclear even though the medium chain triglyceride oils have been used to control weight gain and glycemic index. Here, we show that decanoic acid (DA), a 10-carbon fatty acid and a major component of medium chain triglyceride oils, is a direct ligand of PPARgamma. DA binds and partially activates PPARgamma without leading to adipogenesis. Crystal structure reveals that DA occupies a novel binding site and only partially stabilizes the AF-2 helix. DA also binds weakly to PPARalpha and PPARbeta/delta. Treatments with DA and its triglyceride form improve glucose sensitivity and lipid profiles without weight gain in diabetic mice. Together, these results suggest that DA is a modulating ligand for PPARs, and the structure can aid in designing better and safer PPARgamma-based drugs. PMID- 22039048 TI - Adiponectin stimulates proliferation of adult hippocampal neural stem/progenitor cells through activation of p38 mitogen-activated protein kinase (p38MAPK)/glycogen synthase kinase 3beta (GSK-3beta)/beta-catenin signaling cascade. AB - Adiponectin is the most abundant adipokine secreted from adipocytes. Accumulating evidence suggests that the physiological roles of adiponectin go beyond its metabolic effects. In the present study, we demonstrate that adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) are expressed in adult hippocampal neural stem/progenitor cells (hNSCs). Adiponectin treatment increases proliferation of cultured adult hNSCs in a dose- and time-dependent manner, whereas apoptosis and differentiation of adult hNSCs into neuronal or glial lineage were not affected. Adiponectin activates AMP-activated protein kinase and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways in adult hNSCs. Pretreatment with the p38MAPK inhibitor SB203580, but not the AMP-activated protein kinase inhibitor Compound C, attenuates adiponectin-induced cell proliferation. Moreover, adiponectin induces phosphorylation of Ser-389, a key inhibitory site of glycogen synthase kinase 3beta (GSK-3beta), and this effect can be blocked by inhibition of p38MAPK with SB203580. Levels of total and nuclear beta-catenin, the primary substrate of GSK-3beta, were increased by adiponectin treatment. These results indicate that adiponectin stimulates proliferation of adult hNSCs, via acting on GSK-3beta to promote nuclear accumulation of beta-catenin. Thus, our studies uncover a novel role for adiponectin signaling in regulating proliferation of adult neural stem cells. PMID- 22039049 TI - DNA repair factor MRE11/RAD50 cleaves 3'-phosphotyrosyl bonds and resects DNA to repair damage caused by topoisomerase 1 poisons. AB - MRE11-RAD50 is a highly conserved multifunctional DNA repair factor. Here, we show that MRE11-RAD50 cleaves the covalent 3'-phosphotyrosyl-DNA bonds that join topoisomerase 1 (Top1) to the DNA backbone and that are the hallmark of damage caused by Top1 poisons such as camptothecin. Cleavage generates a 3'-phosphate DNA end that MRE11-RAD50 can resect in an ATP-regulated reaction, to produce a 3' hydroxyl that can prime repair synthesis. The 3'-phosphotyrosyl cleavage activity maps to the MRE11 active site. These results define a new activity of MRE11 and distinguish MRE11-RAD50 functions in repair of Top1-DNA complexes and double strand breaks. PMID- 22039050 TI - Mutant p53 disrupts role of ShcA protein in balancing Smad protein-dependent and independent signaling activity of transforming growth factor-beta (TGF-beta). AB - Biomarkers are lacking for identifying the switch of transforming growth factor beta (TGF-beta) from tumor-suppressing to tumor-promoting. Mutated p53 (mp53) has been suggested to switch TGF-beta to a tumor promoter. However, we found that mp53 does not always promote the oncogenic role of TGF-beta. Here, we show that endogenous mp53 knockdown enhanced cell migration and phosphorylation of ERK in DU145 prostate cancer cells. Furthermore, ectopic expression of mp53 in p53-null PC-3 prostate cancer cells enhanced Smad-dependent signaling but inhibited TGF beta-induced cell migration by down-regulating activated ERK. Reactivation of ERK by the expression of its activator, MEK-1, restored TGF-beta-induced cell migration. Because TGF-beta is known to activate the MAPK/ERK pathway through direct phosphorylation of the adaptor protein ShcA and MAPK/ERK signaling is pivotal to tumor progression, we investigated whether ShcA contributed to mp53 induced ERK inhibition and the conversion of the role of TGF-beta during carcinogenesis. We found that mp53 expression led to a decrease of phosphorylated p52ShcA/ERK levels and an increase of phosphorylated Smad levels in a panel of mp53-expressing cancer cell lines and in mammary glands and tumors from mp53 knock-in mice. By manipulating ShcA levels to regulate ERK and Smad signaling in human untransformed and cancer cell lines, we showed that the role of TGF-beta in regulating anchorage-dependent and -independent growth and migration can be shifted between growth suppression and migration promotion. Thus, our results for the first time suggest that mp53 disrupts the role of ShcA in balancing the Smad dependent and -independent signaling activity of TGF-beta and that ShcA/ERK signaling is a major pathway regulating the tumor-promoting activity of TGF-beta. PMID- 22039051 TI - HIV-1 glycoprotein 41 ectodomain induces activation of the CD74 protein-mediated extracellular signal-regulated kinase/mitogen-activated protein kinase pathway to enhance viral infection. AB - Besides mediating the viral entry process, the human immunodeficiency virus (HIV 1) envelope protein gp41 can bind to many host cell components and regulate cell functions. Using a yeast two-hybrid system, we screened a human bone marrow cDNA library and identified a novel gp41-binding protein, CD74 (the MHC class II associated invariant chain). Here, we report possible biological effects mediated by interaction between gp41 and CD74. We found that HIV-1 gp41 could bind directly to host CD74 in HIV-1-infected cells, and the peptide 6358 derived from gp41 loop region (aa 597-611) could effectively block the gp41-CD74 interaction. As a result of this binding, recombinant soluble gp41 and gp41 peptide 6358 activated the CD74-mediated ERK/MAPK pathway and significantly enhanced HIV-1 infection in vitro. Conversely, the enhancing effect could be suppressed by the recombinant CD74 extracellular domain. These results reveal a novel mechanism underlying gp41 mediation of HIV-1 infection and replication. PMID- 22039052 TI - Identification of membrane-bound variant of metalloendopeptidase neurolysin (EC 3.4.24.16) as the non-angiotensin type 1 (non-AT1), non-AT2 angiotensin binding site. AB - Recently, we discovered a novel non-angiotensin type 1 (non-AT1), non-AT2 angiotensin binding site in rodent and human brain membranes, which is distinctly different from angiotensin receptors and key proteases processing angiotensins. It is hypothesized to be a new member of the renin-angiotensin system. This study was designed to isolate and identify this novel angiotensin binding site. An angiotensin analog, photoaffinity probe 125I-SBpa-Ang II, was used to specifically label the non-AT1, non-AT2 angiotensin binding site in mouse forebrain membranes, followed by a two-step purification procedure based on the molecular size and isoelectric point of the photoradiolabeled binding protein. Purified samples were subjected to two-dimensional gel electrophoresis followed by mass spectrometry identification of proteins in the two-dimensional gel sections containing radioactivity. LC-MS/MS analysis revealed eight protein candidates, of which the four most abundant were immunoprecipitated after photoradiolabeling. Immunoprecipitation studies indicated that the angiotensin binding site might be the membrane-bound variant of metalloendopeptidase neurolysin (EC 3.4.24.16). To verify these observations, radioligand binding and photoradiolabeling experiments were conducted in membrane preparations of HEK293 cells overexpressing mouse neurolysin or thimet oligopeptidase (EC 3.4.24.15), a closely related metalloendopeptidase of the same family. These experiments also identified neurolysin as the non-AT1, non-AT2 angiotensin binding site. Finally, brain membranes of mice lacking neurolysin were nearly devoid of the non-AT1, non AT2 angiotensin binding site, further establishing membrane-bound neurolysin as the binding site. Future studies will focus on the functional significance of this highly specific, high affinity interaction between neurolysin and angiotensins. PMID- 22039053 TI - Determination of target sequence bound by PapX, repressor of bacterial motility, in flhD promoter using systematic evolution of ligands by exponential enrichment (SELEX) and high throughput sequencing. AB - Most uncomplicated urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC). Both motility and adherence are integral to UTI pathogenesis, yet they represent opposing forces. Therefore, it is logical to reciprocally regulate these functions. In UPEC strain CFT073, PapX, a non structural protein encoded by one of the two pap operons encoding P fimbria adherence factor, represses flagella-mediated motility and is a putative member of the winged helix transcription factor family. The mechanism of this repression, however, is not understood. papX is found preferentially in more virulent UPEC isolates, being significantly more prevalent in pyelonephritis strains (53% of isolates) than in asymptomatic bacteriuria (32%) or fecal/commensal (12.5%) strains. To examine PapX structure-function, we generated papX linker insertion and site-directed mutants, which identified two key residues for PapX function (Lys(54) and Arg(127)) within domains predicted by modeling with I-TASSER software to be important for dimerization and DNA binding, respectively. To determine the PapX binding site in the CFT073 genome, systematic evolution of ligands by exponential enrichment (SELEX) in conjunction with high throughput sequencing was utilized for the first time to determine a novel binding site for a bacterial transcription factor. This method identified a 29-bp binding site within the flhDC promoter (TTACGGTGAGTTATTTTAACTGTGCGCAA), centered 410 bp upstream of the flhD translational start site. Gel shift experiments demonstrated that PapX binds directly to this site to repress transcription of flagellar genes. PMID- 22039054 TI - Hyperosmotic stress induces aquaporin-dependent cell shrinkage, polyphosphate synthesis, amino acid accumulation, and global gene expression changes in Trypanosoma cruzi. AB - The protist parasite Trypanosoma cruzi has evolved the ability to transit between completely different hosts and to replicate in adverse environments. In particular, the epimastigote form, the replicative stage inside the vector, is subjected to nutritional and osmotic stresses during its development. In this work, we describe the biochemical and global gene expression changes of epimastigotes under hyperosmotic conditions. Hyperosmotic stress resulted in cell shrinking within a few minutes. Depending on the medium osmolarity, this was followed by lack of volume recovery for at least 2 h or by slow recovery. Experiments with inhibitors, or with cells in which an aquaporin gene (TcAQP1) was knocked down or overexpressed, revealed its importance for the cellular response to hyperosmotic stress. Furthermore, the adaptation to this new environment was shown to involve the regulation of the polyphosphate polymerization state as well as changes in amino acid catabolism to generate compatible osmolytes. A genome-wide transcriptional analysis of stressed parasites revealed down-regulation of genes belonging to diverse functional categories and up-regulation of genes encoding trans-sialidase-like and ribosomal proteins. Several of these changes were confirmed by Northern blot analyses. Sequence analysis of the 3'UTRs of up- and down-regulated genes allowed the identification of conserved structural RNA motifs enriched in each group, suggesting that specific ribonucleoprotein complexes could be of great importance in the adaptation of this parasite to different environments through regulation of transcript abundance. PMID- 22039055 TI - A dormant state modulated by osmotic pressure controls clonogenicity of prostate cancer cells. AB - Cell dormancy constitutes a limiting step of the metastatic process by preventing the proliferation of isolated cancer cells disseminated at distant sites from the primary tumor. The study of cancer cell dormancy is severely hampered by the lack of biological samples so that the mechanisms that regulate cell dormancy have not been extensively explored. In this work, we describe the rapid induction in vitro of a dormant state in prostate cancer cells by exposure to a slightly hypertonic growth medium. This quiescence is observed only when cells are seeded at low density and, once established, requires additional stimuli besides osmotic pressure to be reversed. Media conditioned by cells grown at high density can partially prevent or reverse dormancy, a phenomenon which can be reproduced with citric acid. In addition to this role of small metabolites, inactivation of the p53 and smad pathways also counters the entry into dormancy, whereas exposure to activin A induces it to some extent. Thus, this easily inducible dormancy reproduces several features associated with the dormancy of stem cells and cancer cells in vivo. PMID- 22039056 TI - RECQL4, the protein mutated in Rothmund-Thomson syndrome, functions in telomere maintenance. AB - Telomeres are structures at the ends of chromosomes and are composed of long tracks of short tandem repeat DNA sequences bound by a unique set of proteins (shelterin). Telomeric DNA is believed to form G-quadruplex and D-loop structures, which presents a challenge to the DNA replication and repair machinery. Although the RecQ helicases WRN and BLM are implicated in the resolution of telomeric secondary structures, very little is known about RECQL4, the RecQ helicase mutated in Rothmund-Thomson syndrome (RTS). Here, we report that RTS patient cells have elevated levels of fragile telomeric ends and that RECQL4-depleted human cells accumulate fragile sites, sister chromosome exchanges, and double strand breaks at telomeric sites. Further, RECQL4 localizes to telomeres and associates with shelterin proteins TRF1 and TRF2. Using recombinant proteins we showed that RECQL4 resolves telomeric D-loop structures with the help of shelterin proteins TRF1, TRF2, and POT1. We also found a novel functional synergistic interaction of this protein with WRN during D-loop unwinding. These data implicate RECQL4 in telomere maintenance. PMID- 22039057 TI - Identification of residues in chromodomain helicase DNA-binding protein 1 (Chd1) required for coupling ATP hydrolysis to nucleosome sliding. AB - Chromatin remodelers are ATP-dependent machines responsible for directionally shifting nucleosomes along DNA. We are interested in defining which elements of the chromodomain helicase DNA-binding protein 1 (Chd1) remodeler are necessary and sufficient for sliding nucleosomes. This work focuses on the polypeptide segment that joins the ATPase motor to the C-terminal DNA-binding domain. We identify amino acid positions outside the ATPase motor that, when altered, dramatically reduce nucleosome sliding ability and yet have only ~3-fold reduction in ATPase stimulation by nucleosomes. These residues therefore appear to play a role in functionally coupling ATP hydrolysis to nucleosome sliding, and suggest that the ATPase motor requires cooperation with external elements to slide DNA past the histone core. PMID- 22039058 TI - The nucleotide-binding state of microtubules modulates kinesin processivity and the ability of Tau to inhibit kinesin-mediated transport. AB - The ability of Tau to act as a potent inhibitor of kinesin's processive run length in vitro suggests that it may actively participate in the regulation of axonal transport in vivo. However, it remains unclear how kinesin-based transport could then proceed effectively in neurons, where Tau is expressed at high levels. One potential explanation is that Tau, a conformationally dynamic protein, has multiple modes of interaction with the microtubule, not all of which inhibit kinesin's processive run length. Previous studies support the hypothesis that Tau has at least two modes of interaction with microtubules, but the mechanisms by which Tau adopts these different conformations and their functional consequences have not been investigated previously. In the present study, we have used single molecule imaging techniques to demonstrate that Tau inhibits kinesin's processive run length in an isoform-dependent manner on GDP-microtubules stabilized with either paclitaxel or glycerol/DMSO but not guanosine-5'-((alpha,beta) methyleno)triphosphate (GMPCPP)-stabilized microtubules. Furthermore, the order of Tau addition to microtubules before or after polymerization has no effect on the ability of Tau to modulate kinesin motility regardless of the stabilizing agent used. Finally, the processive run length of kinesin is reduced on GMPCPP microtubules relative to GDP-microtubules, and kinesin's velocity is enhanced in the presence of 4-repeat long Tau but not the 3-repeat short isoform. These results shed new light on the potential role of Tau in the regulation of axonal transport, which is more complex than previously recognized. PMID- 22039060 TI - MBoC 2011: same values, improved feng shui. PMID- 22039061 TI - Give chance a chance. AB - How did I get to become a cell biologist? Or, more generally, why do things happen the way they do? The answer provided by the philosopher Democritus and later adopted by Jacques Monod is "everything existing in the universe is the fruit of chance and necessity." While I read Monod's book Chance and Necessity as an undergraduate student, little did I appreciate the accuracy of this citation and how much of my scientific trajectory would be guided by chance. PMID- 22039062 TI - Science stories: flies, planes, worms, and lasers. AB - "Tell a story," my mother instructs her graduate students as they prepare their talks. I will make use of her advice here, and will tell several short stories. The themes revolve around the practice of science-what motivates us to go into science and how we choose questions once we get there. I also touch on progress in scientific tools, teaching, good mentors, and good colleagues, all of which contribute to making a career in science constantly compelling. PMID- 22039063 TI - Spatial and temporal impacts on a career in science. AB - In cell biology, subcellular locale is critical for the action of signaling molecules, for regulation of gene expression, and for proper cell division. In simple terms, everything must be in the right place at the right time. For my research, I have focused on understanding the role the nuclear pore complex (NPC) plays in maintaining this balance. With eukaryotic transcription in the nucleus and translation in the cytoplasm, highly selective import and export events at the NPC connect these spatially separated processes to allow gene expression. In a similar way, spatial and temporal events have repeatedly impacted my scientific career. In different places and times, interactions with mentors, collaborators, colleagues, and trainees have shaped my research and mentoring philosophies: aim high, fuel your passions, collaborate, and take risks to find supportive environments and challenging projects that impact scientific discovery. PMID- 22039064 TI - A different kind of quarterback. AB - I am not big on celebrations, nor do I accept many invitations to receive awards. There is much work to be done, and the reward is in the doing. I learned this lesson early from my parents, Martha and Robert Guyden. However, I am humbled that anyone would even mention my name in association with E. E. Just. I, like he, was born into a segregated America, and somehow we both found biology. I think Just's life story instigates a discussion on diversity in science, as well it should. However, after reading Tyrone Hayes' (2010 E. E. Just Award recipient) essay from last year, "Diversifying the Biological Sciences: Past Efforts and Future Challenges" (Hayes, 2010), I have little to add on the subject. His words gave voice to my thoughts. That being said, I would like to use these pages to describe my journey into the "Cell" and the people who "hoed the row ahead of me." PMID- 22039065 TI - An evolving paradigm for the secretory pathway? AB - The paradigm that the secretory pathway consists of a stable endoplasmic reticulum and Golgi apparatus, using discrete transport vesicles to exchange their contents, gained important support from groundbreaking biochemical and genetic studies during the 1980s. However, the subsequent development of new imaging technologies with green fluorescent protein introduced data on dynamic processes not fully accounted for by the paradigm. As a result, we may be seeing an example of how a paradigm is evolving to account for the results of new technologies and their new ways of describing cellular processes. PMID- 22039066 TI - Mitosis futures: the past is prologue. AB - The mechanisms by which cells organize and segregate their chromosomes have been under close scrutiny for years, and significant progress has been made in understanding how mitosis works. Modern cell biology has identified most of the molecules that underlie mitotic spindle function, but the ways in which they are organized and controlled to make an effective and accurate cellular machine are exciting subjects for future study. PMID- 22039067 TI - Molecular motors: forty years of interdisciplinary research. AB - A mere forty years ago it was unclear what motor molecules exist in cells that could be responsible for the variety of nonmuscle cell movements, including the "saltatory cytoplasmic particle movements" apparent by light microscopy. One wondered whether nonmuscle cells might have a myosin-like molecule, well known to investigators of muscle. Now we know that there are more than a hundred different molecular motors in eukaryotic cells that drive numerous biological processes and organize the cell's dynamic city plan. Furthermore, in vitro motility assays, taken to the single-molecule level using techniques of physics, have allowed detailed characterization of the processes by which motor molecules transduce the chemical energy of ATP hydrolysis into mechanical movement. Molecular motor research is now at an exciting threshold of being able to enter into the realm of clinical applications. PMID- 22039068 TI - How we discovered fluorescent speckle microscopy. AB - Fluorescent speckle microscopy (FSM) is a method for measuring the movements and dynamic assembly of macromolecular assemblies such as cytoskeletal filaments (e.g., microtubules and actin) or focal adhesions within large arrays in living cells or in preparations in vitro. The discovery of the method depended on recognizing the importance of unexpected fluorescence images of microtubules obtained by time-lapse recording of vertebrate epithelial cells in culture. In cells that were injected with fluorescent tubulin at ~10% of the cytosol pool, microtubules typically appeared as smooth threads with a nearly constant fluorescence intensity. One day, when an unusually low concentration of fluorescent tubulin was injected into cells, the images from a sensitive cooled charge-coupled detector camera showed microtubules with an unusual "speckled" appearance-there were fluorescent dots with variable intensity and spacing along the microtubules. A first thought was that the speckles were an artifact. With further thought, we surmised that the speckles could be telling us something about stochastic association of tubulin dimers with the growing end of a microtubule. Numerous experiments confirmed the latter hypothesis. Subsequently the method we call FSM has proven to be very valuable. The speckles turned out not to be a meaningless artifact, but rather a serendipitous find. PMID- 22039069 TI - In the trenches: lessons for scientists from California's Proposition 71 campaign. AB - I describe a number of valuable lessons I learned from participating in California's Proposition 71 effort about the role that scientists and rigorous scientific advice can play in a public political process. I describe how scientists can provide valuable information and advice and how they can also gain a great deal from the experience that is valuable to a practicing research scientist. Finally, I argue that in the future, building similar broad coalitions to support biomedical and other areas of scientific research will be essential to protect publicly funded science. Thus, a key lesson from the Proposition 71 experience is that engagement of scientists with diverse nonscientific groups can make a big difference and that scientists must actively engage with the public in the future if we are to contribute robustly to the medical and economic health of our communities. PMID- 22039070 TI - Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function. AB - Cholesterol regulates plasma membrane (PM) association and functioning of syntaxin-4 and soluble N-ethylmaleimide-sensitive fusion protein 23 (SNAP23) in the secretory pathway. However, the molecular mechanism and cellular cholesterol pools that determine the localization and assembly of these target membrane SNAP receptors (t-SNAREs) are largely unknown. We recently demonstrated that high levels of annexin A6 (AnxA6) induce accumulation of cholesterol in late endosomes, thereby reducing cholesterol in the Golgi and PM. This leads to an impaired supply of cholesterol needed for cytosolic phospholipase A(2) (cPLA(2)) to drive Golgi vesiculation and caveolin transport to the cell surface. Using AnxA6-overexpressing cells as a model for cellular cholesterol imbalance, we identify impaired cholesterol egress from late endosomes and diminution of Golgi cholesterol as correlating with the sequestration of SNAP23/syntaxin-4 in Golgi membranes. Pharmacological accumulation of late endosomal cholesterol and cPLA(2) inhibition induces a similar phenotype in control cells with low AnxA6 levels. Ectopic expression of Niemann-Pick C1 (NPC1) or exogenous cholesterol restores the location of SNAP23 and syntaxin-4 within the PM. Importantly, AnxA6-mediated mislocalization of these t-SNAREs correlates with reduced secretion of cargo via the SNAP23/syntaxin-4-dependent constitutive exocytic pathway. We thus conclude that inhibition of late endosomal export and Golgi cholesterol depletion modulate t-SNARE localization and functioning along the exocytic pathway. PMID- 22039071 TI - Executive function profile in the offspring of women that smoked during pregnancy. AB - INTRODUCTION: Smoking tobacco during pregnancy results in exposure to the fetal neuroteratogen nicotine. The current study evaluated if the offspring of smokers show abnormalities in maternal ratings of executive function, prevalence of Attention Deficit Hyperactivity Disorder (ADHD), and academic performance. A secondary objective was to determine the utility of online data collection. METHODS: Mothers (N = 357) completed the parent form of the Behavioral Rating Inventory of Executive Function (BRIEF) and provided information about smoking during pregnancy. RESULTS: The internal consistency of the BRIEF when administered electronically was quite satisfactory (Cronbach's alpha = .98). As anticipated, ADHD was more frequently diagnosed in the offspring of women that smoked at least 10 cigarettes/day (odds ratio [OR] = 2.64, 95% CI = 1.22-5.71). Higher (i.e., more problematic) ratings relative to unexposed children (p < .01) were only identified on the total BRIEF score, the Metacognition Index, and on the Initiate, Plan/Organize, and Monitor scales among children exposed to >=10 cigarettes/day. Nicotine-exposed children were also more likely to perform less well than their classmates in math (OR = 2.78, 95% CI = 1.59-4.87) and reading (OR = 2.00, 95% CI = 1.10-3.63), and these academic effects were independent of maternal education levels. CONCLUSIONS: This report provides preliminary evidence that the BRIEF has adequate psychometric properties when administered electronically and that mothers who smoke have offspring with lower executive function proficiency. These findings contribute to a larger literature that indicates that smoking during pregnancy results in adverse reproductive outcomes and, possibly, subtle but enduring deficits in prefrontal function. PMID- 22039072 TI - Tobacco packaging and labeling policies under the U.S. Tobacco Control Act: research needs and priorities. AB - INTRODUCTION: The Family Smoking Prevention and Tobacco Control Act (the "Act"), enacted in June 2009, gave the U.S. Food and Drug Administration authority to regulate tobacco products. The current paper reviews the provisions for packaging and labeling, including the existing evidence and research priorities. METHODS: Narrative review using electronic literature search of published and unpublished sources in 3 primary areas: health warnings, constituent labeling, and prohibitions on the promotional elements of packaging. RESULTS: The Act requires 9 pictorial health warnings covering half of cigarette packages and 4 text warnings covering 30% of smokeless tobacco packages. The Act also prohibits potentially misleading information on packaging, including the terms "light" and "mild," and provides a mandate to require disclosure of chemical constituents on packages. Many of the specific regulatory provisions are based on the extent to which they promote "greater public understanding of the risks of tobacco." As a result, research on consumer perceptions has the potential to shape the design and renewal of health warnings and to determine what, if any, information on product constituents should appear on packages. Research on consumer perceptions of existing and novel tobacco products will also be critical to help identify potentially misleading information that should be restricted under the Act. CONCLUSION: Packaging and labeling regulations required under the Act will bring the United States in line with international standards. There is an immediate need for research to evaluate these measures to guide future regulatory action. PMID- 22039073 TI - Water pipe and smokeless tobacco use among medical students in South Africa. AB - INTRODUCTION: This study sought to determine the sociodemographic and behavioral factors associated with water pipe and smokeless tobacco (SLT) use among a population of medical students in the Pretoria area, South Africa. METHODS: Undergraduate medical students (N = 722) in their 2nd and 6th year of study in 2 medical schools in South Africa completed a self-administered questionnaire during 2008. Information on ever and current use of water pipe and SLT was obtained along with information on sociodemographic variables, alcohol use, and cigarette smoking status. Multiple logistic regression analysis were used to determine factors associated with current use of water pipe and SLT. RESULTS: The mean age of study participants was 23 years. Of the participants, 53% were female and 55% were self-identified as Black Africans. Of the study participants, 18.6% were current water pipe users, 3.1% were current SLT users, while 17.3% were current cigarette smokers. Factors independently associated with current water pipe use were having an alcohol drinking-problem (odds ratio [OR] = 2.43; 95% CI = 1.48-3.40), currently smoking cigarettes (3.40; 2.04-5.67), and reporting exposure to smoking in places other than home (2.51; 1.29-4.90). Compared with Black students, White medical students were more likely to have smoked a water pipe in the past month (3.14; 1.74-5.70) but less likely to have ever used SLT (0.37; 0.19-0.73). CONCLUSIONS: These findings suggest that the use of alternative tobacco products is common among South African medical students and may form part of a pattern of risk-taking behavior. Furthermore, there appear to be cultural differences in the use of certain tobacco products. PMID- 22039074 TI - Chromosome 20 shows linkage with DSM-IV nicotine dependence in Finnish adult smokers. AB - INTRODUCTION: Chromosome 20 has previously been associated with nicotine dependence (ND) and smoking cessation. Our aim was to replicate and extend these findings. METHODS: First, a total of 759 subjects belonging to 206 Finnish families were genotyped with 18 microsatellite markers residing on chromosome 20, in order to replicate previous linkage findings. Then, the replication data were combined to an existing whole-genome linkage data resulting in a total of 1,302 genotyped subjects from 357 families. ND diagnosed by DSM-IV criteria, the Fagerstrom Test for Nicotine Dependence (FTND) score, and the lifetime maximum number of cigarettes smoked within a 24-hr period (MaxCigs24) were used as phenotypes in the nonparametric linkage analyses. RESULTS: We replicated previously reported linkage to DSM-IV ND, with a maximum logarithm of odd (LOD) score of 3.8 on 20p11, with females contributing more (maximum LOD [MLOD] score 3.4 on 20q11) than males (MLOD score 2.6 on 20p11). With the combined sample, a suggestive LOD score of 2.3 was observed for DSM-IV ND on 20p11. Sex-specific analyses revealed that the signal was driven by females with a maximum LOD score of 3.3 (on 20q11) versus LOD score of 1.3 in males (on 20q13) in the combined sample. No significant linkage signals were obtained for FTND or MaxCigs24. CONCLUSIONS: Our results provide further evidence that chromosome 20 harbors genetic variants influencing ND in adult smokers. PMID- 22039075 TI - Monitoring tobacco-specific N-nitrosamines and nicotine in novel Marlboro and Camel smokeless tobacco products: findings from Round 1 of the New Product Watch. AB - INTRODUCTION: Information on chemical composition of the new oral "spitless" smokeless tobacco products is scarce, and it is not clear whether there is some variability as a function of purchase place or time due to either unintended or intended manufacturing variations or other conditions. METHODS: We analyzed tobacco-specific N-nitrosamines (TSNA) and nicotine in Marlboro Snus, Camel Snus, and dissolvable Camel products Orbs, Sticks, and Strips that were purchased in various regions of the country during the summer of 2010. RESULTS: A total of 117 samples were received from different states representing six regions of the country. Levels of unprotonated nicotine in Marlboro Snus and Camel Snus varied significantly by regions, with the differences between the highest and the lowest average regional levels being relatively small in Marlboro Snus (~1.3-fold) and large in Camel Snus (~3-fold). Some regional variations in TSNA levels were also observed. Overall, Camel Snus had significantly higher TSNA levels than Marlboro Snus, and Camel Strips had the lowest TSNA levels among all novel products analyzed here. The amount of unprotonated nicotine in the dissolvable Camel products was comparable to the levels found in Marlboro Snus. CONCLUSIONS: Our study demonstrates some regional variations in the levels of nicotine and TSNA in Marlboro and Camel novel smokeless tobacco products. Continued monitoring of this category of products is needed as the existing products are being test marketed and modified, and new products are being introduced. This information is particularly important given its relevance to Food and Drug Administration regulation of tobacco products. PMID- 22039076 TI - Measuring exposure to protobacco marketing and media: a field study using ecological momentary assessment. AB - INTRODUCTION: The aims of this study were to validate ecological momentary assessment (EMA) as a method for measuring exposure to tobacco-related marketing and media and to use this method to provide detailed descriptive data on college students' exposure to protobacco marketing and media. METHODS: College students (n = 134; ages 18-24 years) recorded their exposures to protobacco marketing and media on handheld devices for 21 consecutive days. Participants also recalled exposures to various types of protobacco marketing and media at the end of the study period. RESULTS: Retrospectively recalled and EMA-based estimates of protobacco marketing exposure captured different information. The correlation between retrospectively recalled and EMA-logged exposures to tobacco marketing and media was moderate (r = .37, p < .001), and EMA-logged exposures were marginally associated with the intention to smoke at the end of the study, whereas retrospective recall of exposure was not. EMA data showed that college students were exposed to protobacco marketing through multiple channels in a relatively short period: Exposures (M = 8.24, SD = 7.85) occurred primarily in the afternoon (42%), on weekends (35%), and at point-of-purchase locations (68%) or in movies/TV (20%), and exposures to Marlboro, Newport, and Camel represented 56% of all exposures combined and 70% of branded exposures. CONCLUSIONS: Findings support the validity of EMA as a method for capturing detailed information about youth exposure to protobacco marketing and media that are not captured through other existing methods. Such data have the potential to highlight areas for policy change and prevention in order to reduce the impact of tobacco marketing on youth. PMID- 22039077 TI - The reliability of puff topography and subjective responses during ad lib smoking of a single cigarette. AB - INTRODUCTION: Acute smoking behavior (i.e., puff topography) and subjective responses during the ad lib smoking of a single cigarette in the laboratory may provide useful measures of smoking reinforcement and reward, respectively. However, the reliability of such measures is not clear, leaving uncertain the utility of a single assessment of smoking behavior as an individual difference measure. METHODS: Dependent smokers (N = 94) smoked normally prior to each of 4 laboratory sessions during which they were instructed to smoke 1 cigarette of their preferred brand in ad libitum and unblinded fashion and then rate it for subjective effects. Puff topography (puff number, total volume, and maximum volume) was assessed via portable Clinical Research Support System device. Subjective reward and perception were assessed by visual analog scales of "liking" and "how strong," respectively. The reliability of puff topography and subjective measures was determined across days by intra-class correlations (ICCs). Differences due to sex and nicotine dependence (high and low Fagerstrom Test for Nicotine Dependence score) were also examined. RESULTS: Reliability was highly significant for each measure. ICCs were .70 for total puff volume, .60 for maximum puff volume, .73 for puff number, .64 for liking, and .78 for how strong. Reliability generally did not differ by sex or dependence, but absolute values for total volume and maximum puff volume were greater in men and in high dependent smokers. Liking was also greater in high dependent smokers. CONCLUSIONS: Puff topography and subjective measures during the ad lib smoking of a single cigarette are highly reliable. Smoking responses during a single ad lib smoking session may be useful in identifying stable individual differences in smoking reinforcement and reward. PMID- 22039078 TI - Epratuzumab-SN-38: a new antibody-drug conjugate for the therapy of hematologic malignancies. AB - We previously found that slowly internalizing antibodies conjugated with SN-38 could be used successfully when prepared with a linker that allows approximately 50% of the IgG-bound SN-38 to dissociate in serum every 24 hours. In this study, the efficacy of SN-38 conjugates prepared with epratuzumab (rapidly internalizing) and veltuzumab (slowly internalizing), humanized anti-CD22 and anti-CD20 IgG, respectively, was examined for the treatment of B-cell malignancies. Both antibody-drug conjugates had similar nanomolar activity against a variety of human lymphoma/leukemia cell lines, but slow release of SN 38 compromised potency discrimination in vitro even against an irrelevant conjugate. When SN-38 was stably linked to the anti-CD22 conjugate, its potency was reduced 40- to 55-fold. Therefore, further studies were conducted only with the less stable, slowly dissociating linker. In vivo, similar antitumor activity was found between CD22 and CD20 antibody-drug conjugate in mice-bearing Ramos xenografts, even though Ramos expressed 15-fold more CD20 than CD22, suggesting that the internalization of the epratuzumab-SN-38 conjugate (Emab-SN-38) enhanced its activity. Emab-SN-38 was more efficacious than a nonbinding, irrelevant IgG SN-38 conjugate in vivo, eliminating a majority of well-established Ramos xenografts at nontoxic doses. In vitro and in vivo studies showed that Emab-SN-38 could be combined with unconjugated veltuzumab for a more effective treatment. Thus, Emab-SN-38 is active in lymphoma and leukemia at doses well below toxic levels and therefore represents a new promising agent with therapeutic potential alone or combined with anti-CD20 antibody therapy. PMID- 22039079 TI - Stellate ganglion block for the management of hot flashes and sleep disturbances in breast cancer survivors: an uncontrolled experimental study with 24 weeks of follow-up. AB - BACKGROUND: We studied the stellate ganglion block (SGB) recently suggested for the treatment of severe vasomotor symptoms and sleep disturbances in breast cancer survivors. Following an initial pilot study, which focused on the acceptability and safety of SGB for this important problem, we evaluated its short- and long-term efficacy. MATERIALS AND METHODS: Postmenopausal breast cancer survivors with severe vasomotor symptoms resistant to standard nonhormonal pharmacological intervention were eligible. Diaries were used to measure daily hot flash scores (frequency and intensity) and sleep quality (Pittsburgh Sleep Quality Index) during scheduled visits at baseline, 1, 4, 12 and 24 weeks following the SGB. Efficacy data were analyzed using longitudinal regression models. RESULTS: Thirty-four patients participated and none refused the SGB procedure. Most patients received more than one SGB. The pilot study found SGB to be safe. In the main study, hot flash scores were reduced from baseline by 64% [95% confidence interval (CI) -74% to -49%] and 47% (95% CI -62% to -27%) at weeks 1 and 24, respectively. The odds ratio of better sleep quality relative to baseline was 3.4 at week 1 (95% CI 1.6-7.2) and 4.3 at week 24 (95% CI 1.9-9.8). CONCLUSION: In the short term, SGB appears to be an effective treatment with acceptable morbidity for some breast cancer survivors with therapy-resistant vasomotor symptoms and/or sleep disturbances. Although sleep quality was maintained out to 24 weeks the efficacy of SGB for hot flashes was reduced over time. A randomized controlled trial is needed to confirm these findings. PMID- 22039080 TI - Outcome of special types of luminal breast cancer. AB - BACKGROUND: The identification of special types of breast cancer might be of value in assessing prognosis and predicting response to therapy. METHODS: A total of 7372 consecutive patients with immunohistochemically defined luminal invasive breast cancer operated at the European Institute of Oncology between 1997 and 2005 were included. We then explored patterns of recurrence by histological type. Median follow-up was 5.8 years. RESULTS: Tumors from 5707 patients were classified as invasive ductal cancer (IDC) not otherwise specified (NOS), 851 lobular, 338 mixed ductal and lobular, 250 cribriform, 143 mucinous and 83 tubular carcinomas. Compared with IDC NOS disease-free survival (DFS) was significantly longer in patients with cribriform tumors [5-year DFS 97.9% versus 87.4%; hazard ratio (HR) = 0.48; P = 0.015) and in pooled cribriform plus tubular carcinomas (5-year DFS 98.7% versus 87.4%; HR = 0.45; P = 0.005). Mucinous tumors presented similar DFS if compared with IDC (5-year DFS 93 % versus 87.4%; HR = 1.03; P = 0.91). Conversely, DFS was poorer for patients with lobular carcinoma (5-year DFS 86.8% versus 87.4%; HR = 1.27; P = 0.01). CONCLUSIONS: The diagnosis of tubular, cribriform and lobular carcinomas carry distinct prognostic implications. The identification of these special types has a significant utility in luminal breast cancer and should be considered in therapeutic algorithms. PMID- 22039081 TI - Advanced well-differentiated/dedifferentiated liposarcomas: role of chemotherapy and survival. AB - BACKGROUND: Data regarding the role of systemic therapy in patients with advanced well-differentiated/dedifferentiated liposarcomas (WDLPS/DDLPS) are limited. METHODS: From 2000 to 2010, 208 patients with advanced WDLPS/DDLPS received chemotherapy in 11 participating institutions. Clinical and pathological data were collected by reviewing medical records. RESULTS: Median age was 63 years (range 32-84). Combination chemotherapy was delivered in 85 cases (41%) and single agent in 123 cases (59%), respectively. One hundred and seventy-one patients (82%) received an anthracycline-containing regimen. Using RECIST, objective response was observed in 21 patients (12%), all treated with anthracyclines. Median progression-free survival (PFS) was 4.6 months [95% confidence interval (CI) 3.3-5.9]. On multivariate analysis, age and performance status (PS) were the sole factors significantly associated with poor PFS. Median overall survival (OS) was 15.2 months (95% CI 11.8 -18.7). On multivariate analysis, grade and PS were the sole factors significantly associated with OS. CONCLUSIONS: Chemotherapy was associated with clinical benefit in 46% of patients with advanced WDLPS/DDLPS. OS remains poor, even though visceral metastatic disease is less frequent than in other sarcomas. PMID- 22039082 TI - Professional failure: how do oncologists feel it? PMID- 22039083 TI - Alcohol drinking and bladder cancer risk: a meta-analysis. AB - BACKGROUND: We aimed at investigating the risk of bladder cancer at different levels of alcohol consumption by conducting a meta-analysis of epidemiological studies. PATIENTS AND METHODS: In October 2010, we carried out a systematic literature search in the Medline database, using PubMed. We identified 16 case control and 3 cohort studies, including a total of 11 219 cases of bladder cancer, satisfying the inclusion criteria for this meta-analysis. Moderate alcohol intake was defined as <3 drinks per day (i.e. <37.5 g of ethanol per day) and heavy intake as >=3 drinks/day. Pooled estimates of the relative risks (RR) and the corresponding 95% confidence intervals (CI) were calculated using random effects models. RESULTS: Compared with non-drinkers, the pooled RRs of bladder cancer were 1.00 (95% CI 0.92-1.09) for moderate and 1.02 (95% CI 0.78-1.33) for heavy alcohol drinkers. When we excluded four studies that did not adjust for tobacco smoking, the corresponding estimates were 0.98 (95% CI 0.89-1.07) and 0.97 (95% CI 0.72-1.31). CONCLUSIONS: This meta-analysis of epidemiological studies provides definite evidence on the absence of any material association between alcohol drinking and bladder cancer risk, even at high levels of consumption. PMID- 22039084 TI - Retreatment with trastuzumab-based therapy after disease progression following lapatinib in HER2-positive metastatic breast cancer. AB - BACKGROUND: Preclinical data suggest that treatment with lapatinib reinduces sensitivity to trastuzumab in human epidermal growth factor receptor 2(HER2) positive breast cancer cells. PATIENTS AND METHODS: Between January 2007 and November 2010, 179 HER2-positive metastatic breast cancer patients were treated with lapatinib and capecitabine at nine Italian institutions. We evaluated the clinical outcome of 69 patients (38.5%) retreated with trastuzumab after lapatinib progression. RESULTS: Visceral metastases were identified in 51 (74%) and brain metastases in 16 patients (23%). All patients were pretreated with both trastuzumab- and lapatinib-based therapy. We observed with retreatment with trastuzumab-based therapy: 1 complete remission (2%), 18 partial remission (29%) and 10 stable disease >=6 months (14%) and 47% of clinical benefit (CB). Median duration of response was 8.1 months [95% confidence interval (CI) 5.5-10.7]. No unexpected toxic effects occurred. At a median follow-up of 13 months, median progression-free survival was 4.9 months (95% CI 4.2-5.6) and overall survival (OS) 19.4 months (95% CI 14.0-25.0). Median OS was longer for patients experiencing CB (not reached versus 13.4 months for patients without CB, P = 0.002). Brain involvement was associated with lower median OS (17.3 versus 23.3 months for patients without brain disease; P = 0.021). CONCLUSION: Retreatment with trastuzumab-based therapy showed CB in 47% of patients progressing during lapatinib-based therapy, leading to a prolonged OS. PMID- 22039085 TI - Perioperative docetaxel, cisplatin, and 5-fluorouracil (DCF) for locally advanced esophageal and gastric adenocarcinoma: a multicenter phase II trial. AB - BACKGROUND: Although perioperative chemotherapy for esophagogastric adenocarcinoma (ADC) improves survival, the overall poor prognosis suggests that further refinement of treatment is required. Docetaxel, cisplatin, and 5 fluorouracil (5-FU) (DCF) is effective for metastatic ADC of the upper gastrointestinal (GI) tract; we thus sought to investigate the efficacy of this regimen in patients with resectable disease. PATIENTS AND METHODS: Patients with resectable ADC of the upper GI tract received DCF [docetaxel (Taxotere) 75 mg/m(2) I.V. day 1, cisplatin 75 mg/m(2) I.V. day 1, 5-FU 750 mg/m(2) continuous infusion for 120 h, every 3 weeks] for three cycles before and after resection. Primary end point was complete resection; secondary end points were response, toxicity, surgical morbidity, and overall survival. RESULTS: Forty-three patients with ADC of the esophagus (11), gastroesophageal junction (25), or stomach (7) started treatment and 86% completed all preoperative cycles with grade 3-4 toxicity arising in 47%. Metabolic response to chemotherapy (reduction in maximal standard uptake value >35%) was achieved in 25/33 (76%) patients. Surgery was carried out in 41/43 and complete resection was achieved in all 41 patients with pathologic complete response in 4/41. Postoperative chemotherapy was started in 29 patients and completed in 24. Three-year overall survival was 60%. CONCLUSION: Perioperative DCF is a tolerable and highly effective regimen for the treatment of esophagogastric ADC. PMID- 22039086 TI - Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised controlled trial of Capecitabine, Bevacizumab and Mitomycin C. AB - BACKGROUND: In an ageing population, a greater proportion of geriatric patients will be considered for systemic chemotherapy. Colorectal cancer (CRC) is a common malignancy and will be a major health issue in geriatrics. We used the MAX population to investigate whether age affected the improved outcome found in CRC when bevacizumab is added to capecitabine chemotherapy. PATIENTS AND METHODS: MAX, a three arm study of Capecitabine (C) versus CBevacizumab (CB) versus CBMitomycin C (CBM), found an improvement in progression-free survival (PFS), with addition of B [+/- mitomycin C (MMC)] to C. This analysis assesses the effect of adding B (+/- MMC) to C on PFS, overall survival (OS), response rate (RR), toxicity and dose intensity in geriatric patients (age >= 75 years). RESULTS: Ninety-nine patients (21%) were aged 75-86 years. Baseline characteristics were well balanced. Eighty-eight per cent commenced C at the lower optional dose of 2000 mg/m(2)/day; days 1-14, q21 (61% for <75 years) and 88% were Eastern Cooperative Oncology Group 0-1. Co-morbidities were as expected in this population. The addition of B significantly improved PFS in geriatric patients(C 5.8 months versus CB 8.8 months, Hazard ratio (HR) 0.65 and C versus CBM 10.4 months HR 0.38). The interaction test for OS, RR and PFS revealed no impact of age. Dose intensity was maintained >90% in all patients. There were no major differences in toxicity patterns between age cohorts. CONCLUSIONS: Addition of B to C significantly improved PFS in this geriatric population, with similar benefits to those aged <75 years. Treatment was well tolerated with no signal of increased toxicity (including thromboembolism) when compared with those aged <75 years. PMID- 22039087 TI - Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study. AB - BACKGROUND: Induction chemotherapy has been suggested to impact on preoperative chemoradiation efficacy in locally advanced rectal cancer (LARC). To evaluate in LARC patients, the feasibility and efficacy of a short intense course of induction oxaliplatin before preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: Patients with T2-T4/N+ rectal adenocarcinoma were randomly assigned to arm A-preoperative CRT with 5-fluorouracil (5-FU) continuous infusion followed by surgery-or arm B-induction oxaliplatin, folinic acid and 5-FU followed by CRT and surgery. The primary end point was the rate of ypT0-1N0 stage achievement. RESULTS: Fifty seven patients were randomly assigned (arm A/B: 29/28) and evaluated for planned interim analysis. On an intention-to-treat basis, the ypT0 1N0 rate for arms A and B were 34.5% (95% CI: 17.2% to 51.8%) and 32.1% (95% CI: 14.8% to 49.4%), respectively, and the study therefore was closed prematurely for futility. There were no statistically significant differences in other end points including pathological complete response, tumor regression and sphincter preservation. Completion of the preoperative CRT sequence was similar in both groups. Grade 3/4 toxicity was significantly higher in arm B. CONCLUSIONS: Short intense induction oxaliplatin is feasible in LARC patients without compromising the preoperative CRT completion, although the current analysis does not indicate increased locoregional impact on standard therapy. PMID- 22039088 TI - PIK3CA exon 20 mutations as a potential biomarker for resistance to anti-EGFR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis. AB - BACKGROUND: We conducted a systematic review and meta-analysis to dissect the association between PIK3CA mutations and resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) according to PIK3CA exon of mutations in metastatic colorectal cancer (mCRC). METHODS: We systematically identified studies exploring the association between PIK3CA mutations and clinical outcomes of mCRC patients treated with anti-EGFR MoAbs. The primary clinical outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed effect model or random effect model according to heterogeneity between studies. RESULTS: Thirteen studies were considered eligible, with 576 mCRC patients included. In KRAS wild-type mCRC patients, we observed a lower ORR in patients with PIK3CA exon 20 mutations [3 studies, 377 patients; ORR = 0% versus 37%; RR = 0.25; 95% confidence interval (CI) 0.05-1.19; P = 0.082], although the result was not statistically significant because of the small sample size. Only one study provided survival data according to the PIK3CA exon of the mutations, in which PIK3CA exon 20 mutations were statistically significantly associated with shorter PFS (HR = 2.52; 95% CI 1.33 4.78; P = 0.013) and OS (HR = 3.29; 95% CI 1.60-6.74; P = 0.006) in KRAS wild type mCRC patients treated with anti-EGFR MoAbs. The predictive power of exon 20 mutation is greater than exon 9 mutations and all exons mutations in terms of ORR, PFS, and OS. CONCLUSION: These analyses suggest that PIK3CA exon 20 mutations may be a potential biomarker for resistance to anti-EGFR MoAbs in KRAS wild-type mCRC. PMID- 22039089 TI - Frontline chemotherapy with bortezomib-containing combinations improves response rate and survival in primary plasma cell leukemia: a retrospective study from GIMEMA Multiple Myeloma Working Party. AB - BACKGROUND: The best therapeutic approach for primary plasma cell leukemia (PPCL) remains unknown so far. In very limited studies, the poor clinical outcome of this aggressive variant of multiple myeloma seemed to be ameliorated by the use of the proteasome inhibitor bortezomib. Aiming to provide more consolidated data, this multicenter retrospective survey focused on unselected and previously untreated PPCL patients who had received bortezomib as frontline therapy. PATIENTS AND METHODS: Twenty-nine patients with PPCL were collected. Bortezomib was given at standard doses and schedules, in various combinations with dexamethasone, thalidomide, doxorubicin, melphalan, prednisone, vincristine, and cyclophosphamide. RESULTS: An overall response rate of 79% was observed, with 38% of at least very good partial remission. Grade 3-4 hematological, neurological, infectious, and renal toxic effects occurred in 20%, 21%, 16%, and 4% of patients, respectively. After a median follow-up of 24 months, 16 patients were alive (55%), 12 of whom were in remission phase and 4 relapsed. The best long term results were achieved in patients who received stem-cell transplantation after bortezomib induction. CONCLUSION: Bortezomib, used as initial therapy, is able to increase the percentage and the quality of responses in PPCL patients, producing a significant improvement of survival. PMID- 22039091 TI - Postprogression survival for first-line chemotherapy of patients with advanced non-small-cell lung cancer. AB - BACKGROUND: Given the growing number of drugs available for non-small-cell lung cancer (NSCLC), an effect of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. We examined the relation between postprogression survival (PPS) and OS in phase III trials of first-line chemotherapy for advanced NSCLC. PATIENTS AND METHODS: A literature search identified 69 trials that were published during the past decade. We partitioned OS into progression-free survival (PFS) and PPS and evaluated the relation between OS and either PFS or PPS. We also examined whether any association might be affected by the year of completion of trial enrollment. RESULTS: The average PPS was longer in recent trials than in older trials (6.5 versus 4.4 months, P < 0.0001). For all trials, PPS was strongly associated with OS (r = 0.82), whereas PFS was moderately associated with OS (r = 0.43). The correlation between OS and PPS in recent trials was stronger than that in older trials (r = 0.89 and 0.66). CONCLUSIONS: Our findings indicate that, especially for recent trials, PPS is highly associated with OS in first-line chemotherapy for advanced NSCLC, whereas PFS is only moderately associated with OS. PMID- 22039090 TI - An observational study of the prevalence and incidence of comorbid conditions in older women with breast cancer. AB - BACKGROUND: Longitudinal analyses of comorbid conditions in women with breast cancer are few. METHODS: Using Surveillance, Epidemiology, and End Results Medicare data, we included 51,950 women aged>=66 years with in situ and stage I to IV breast cancer diagnosed in 1998-2002. We identified the prevalence and incidence of 34 comorbid conditions in these women, as well as in a matched cohort without cancer whose rates were standardized to the age and race/ethnicity distribution of the cancer patients. We also estimated rates of office encounters and diagnostic or testing procedures during the 12 months before diagnosis. RESULTS: The prevalence of most conditions at diagnosis was comparable among breast cancer and noncancer patients. New conditions after diagnosis were more common in breast cancer patients, and the incidence rates increased with higher stage at diagnosis. Before diagnosis, women presenting with stage IV disease had 41% [95% confidence interval (CI) 38% to 43%] fewer physician encounters and 34% (95% CI 24% to 31%) fewer unique diagnostic tests than women diagnosed with carcinoma in situ. CONCLUSIONS: Many comorbid conditions are identified as a consequence of the breast cancer diagnosis. There appears to be an important contribution from a lack of interaction with the health care system before diagnosis. PMID- 22039092 TI - Quality of work life in doctors working with cancer patients. AB - BACKGROUND: Although studies have shown that medical residents experience poor psychological health and poor organizational conditions, their quality of work life (QWL) had not been measured. A new tool, the Quality of Work Life Systemic Inventory (QWLSI), proposes to fill the gap in the definition and assessment of this concept. AIMS: To confirm the convergent validity of the QWLSI, analyse Belgian medical residents' QWL with the QWLSI and discuss an intervention methodology based on the analysis of the QWLSI. METHODS: One hundred and thirteen medical residents participated between 2002 and 2006. They completed the QWLSI, the Maslach Burnout Inventory and the Job Stress Survey to confirm the correspondence between these three tools. RESULTS: Residents' low QWL predicted high emotional exhaustion (beta = 0.282; P < 0.01) and job stress (beta = 0.370; P < 0.001) levels, confirming the convergent validity. This sample of medical residents had an average QWL (MU = 5.8; SD = 3.1). However, their QWL was very low for three subscales: arrangement of work schedule (MU = 9; SD = 6.3), support offered to employee (MU = 7.6; SD = 6.1) and working relationship with superiors (MU = 6.9; SD = 5.3). CONCLUSIONS: The results confirm that the QWLSI can provide an indication of workers' health well-being and of organizational performance in different areas of work life. The problem factors found among Belgian medical residents suggest that prevention should focus on reduction of work hours, development of support and change in leadership style. PMID- 22039093 TI - Association of the R67X and W303X non-sense polymorphisms in the protein Z dependent protease inhibitor gene with idiopathic recurrent miscarriage. AB - Protein Z-dependent protease inhibitor (ZPI) is a 72 kDa single-chain serpin which inhibits the activated coagulation factors X and XI. Two non-sense polymorphisms of ZPI, R67X and W303X, were recently identified, and were linked with a prothrombotic state. Here, we investigated the association of the R67X (728C>T) and W303X (1438G>A) variants in the ZPI gene with recurrent spontaneous miscarriage (RSM). This was a case-control study involving a total of 288 women with a history of two consecutive or >=3 non-consecutive pregnancy losses between 8 and 12th week of gestation, along with 304 age-matched and ethnically matched multiparous control women, with no personal or family history of pregnancy complications. The minor allele frequency of R67X (P = 0.003) and W303X (P = 0.014) were higher in RSM cases than in control women. Both single-nucleotide polymorphisms were significantly associated with RSM under the dominant genetic association model, and were in moderate linkage disequilibrium (D' = 0.412; P < 0.001). Taking the common (728)C/(1438)G haplotype as reference, multivariate analysis confirmed the positive association of (728)T/(1438)G [P = 0.043; odds ratio (OR) = 2.25; 95% confidence interval (CI) = 1.03-4.90], and (728)T/(1438)A (P = 0.022; OR = 3.93; 95% CI = 1.23-12.59) haplotypes with increased RSM risk. These differences remained significant after controlling for some covariates. These results demonstrate that both ZPI R67X and W303X non-sense variants and specific ZPI haplotypes are significantly associated with RSM. PMID- 22039095 TI - Cancer mortality among female and male workers occupationally exposed to inorganic lead in the printing industry. AB - OBJECTIVE: Evaluation of the carcinogenicity of lead for humans has been based primarily on the results of studies on occupationally exposed men, although gender differences in lead metabolism have been reported. In addition, most of the previous studies have been limited by a failure to identify and control for co-exposures to other known occupational carcinogens. The present study follows an industrial cohort of workers, mostly women, with moderate lead exposure and no confounding by other occupational exposures. METHODS: Workers, employed at least 2 years between 1950 and 1978 in manual and mechanical (linotype) typesetting and type foundries in 27 printing plants in Moscow, were included in the cohort, which comprised 1423 men and 3102 women. The cohort was followed up during 1979 2003 and contributed 93,682 person-years of observation. Follow-up was 97.7% complete. Standardised mortality ratios (SMRs) and 95% CIs, based on mortality rates of the Moscow general population and adjusted for gender, age and calendar time, were calculated for the total cohort as well as subcohorts stratified by various exposure parameters. RESULTS: Among women, mortality from all causes, circulatory diseases and all cancers combined was lower than that in the Moscow general population and was similar across work groups. Among men, there was excess overall mortality, mainly due to increased mortality from ischaemic heart disease. For both sexes, no significant excess risk for any cancer site was observed, although some dose-response patterns were found. In the overall cohort, mortality from cancers of the kidney and pancreas increased up to twofold in the highest tertile of cumulative lead exposure based on duration and a relative ranking of the three subcohorts (9 deaths; SMR=2.12, 95% CI 1.10 to 4.07) and (18 deaths; SMR=2.32, 95% CI 1.46 to 3.68), respectively. Similar mortality trends for these two cancers were found in analyses by gender. CONCLUSIONS: Consistencies by sex and exposure level make a strong case for a link between exposure to inorganic lead and cancers of the kidney and pancreas. PMID- 22039094 TI - alpha7beta2 nicotinic acetylcholine receptors assemble, function, and are activated primarily via their alpha7-alpha7 interfaces. AB - We investigated assembly and function of nicotinic acetylcholine receptors (nAChRs) composed of alpha7 and beta2 subunits. We measured optical and electrophysiological properties of wild-type and mutant subunits expressed in cell lines and Xenopus laevis oocytes. Laser scanning confocal microscopy indicated that fluorescently tagged alpha7 and beta2 subunits colocalize. Forster resonance energy transfer between fluorescently tagged subunits strongly suggested that alpha7 and beta2 subunits coassemble. Total internal reflection fluorescence microscopy revealed that assemblies localized to filopodia-like processes of SH-EP1 cells. Gain-of-function alpha7 and beta2 subunits confirmed that these subunits coassemble within functional receptors. Moreover, alpha7beta2 nAChRs composed of wild-type subunits or fluorescently tagged subunits had pharmacological properties similar to those of alpha7 nAChRs, although amplitudes of alpha7beta2 nAChR-mediated, agonist-evoked currents were generally ~2-fold lower than those for alpha7 nAChRs. It is noteworthy that alpha7beta2 nAChRs displayed sensitivity to low concentrations of the antagonist dihydro-beta erythroidine that was not observed for alpha7 nAChRs at comparable concentrations. In addition, cysteine mutants revealed that the alpha7-beta2 subunit interface does not bind ligand in a functionally productive manner, partly explaining lower alpha7beta2 nAChR current amplitudes and challenges in identifying the function of native alpha7beta2 nAChRs. On the basis of our findings, we have constructed a model predicting receptor function that is based on stoichiometry and position of beta2 subunits within the alpha7beta2 nAChRs. PMID- 22039096 TI - Fixed FEV(1)/FVC ratio <0.7 for identifying airflow limitation: not a good idea in occupational settings. PMID- 22039097 TI - Sensitisation to common allergens and respiratory symptoms in endotoxin exposed workers: a pooled analysis. AB - OBJECTIVE: To test the hypotheses that current endotoxin exposure is inversely associated with allergic sensitisation and positively associated with non allergic respiratory diseases in four occupationally exposed populations using a standardised analytical approach. METHODS: Data were pooled from four epidemiological studies including 3883 Dutch and Danish employees in veterinary medicine, agriculture and power plants using biofuel. Endotoxin exposure was estimated by quantitative job-exposure matrices specific for the study populations. Dose-response relationships between exposure, IgE-mediated sensitisation to common allergens and self-reported health symptoms were assessed using logistic regression and generalised additive modelling. Adjustments were made for study, age, sex, atopic predisposition, smoking habit and farm childhood. Heterogeneity was assessed by analysis stratified by study. RESULTS: Current endotoxin exposure was dose-dependently associated with a reduced prevalence of allergic sensitisation (ORs of 0.92, 0.81 and 0.66 for low mediate, high mediate and high exposure) and hay fever (ORs of 1.16, 0.81 and 0.58). Endotoxin exposure was a risk factor for organic dust toxic syndrome, and levels above 100 EU/m(3) significantly increased the risk of chronic bronchitis (p<0.0001). Stratification by farm childhood showed no effect modification except for allergic sensitisation. Only among workers without a farm childhood, endotoxin exposure was inversely associated with allergic sensitisation. Heterogeneity was primarily present for biofuel workers. CONCLUSIONS: Occupational endotoxin exposure has a protective effect on allergic sensitisation and hay fever but increases the risk for organic dust toxic syndrome and chronic bronchitis. Endotoxin's protective effects are most clearly observed among agricultural workers. PMID- 22039098 TI - Crystal structure of a heterodimer of editosome interaction proteins in complex with two copies of a cross-reacting nanobody. AB - The parasite Trypanosoma brucei, the causative agent of sleeping sickness across sub-Saharan Africa, depends on a remarkable U-insertion/deletion RNA editing process in its mitochondrion. A approximately 20 S multi-protein complex, called the editosome, is an essential machinery for editing pre-mRNA molecules encoding the majority of mitochondrial proteins. Editosomes contain a common core of twelve proteins where six OB-fold interaction proteins, called A1-A6, play a crucial role. Here, we report the structure of two single-strand nucleic acid binding OB-folds from interaction proteins A3 and A6 that surprisingly, form a heterodimer. Crystal growth required the assistance of an anti-A3 nanobody as a crystallization chaperone. Unexpectedly, this anti-A3 nanobody binds to both A3(OB) and A6, despite only ~40% amino acid sequence identity between the OB folds of A3 and A6. The A3(OB)-A6 heterodimer buries 35% more surface area than the A6 homodimer. This is attributed mainly to the presence of a conserved Pro rich loop in A3(OB). The implications of the A3(OB)-A6 heterodimer, and of a dimer of heterodimers observed in the crystals, for the architecture of the editosome are profound, resulting in a proposal of a 'five OB-fold center' in the core of the editosome. PMID- 22039099 TI - The MOF-containing NSL complex associates globally with housekeeping genes, but activates only a defined subset. AB - The MOF (males absent on the first)-containing NSL (non-specific lethal) complex binds to a subset of active promoters in Drosophila melanogaster and is thought to contribute to proper gene expression. The determinants that target NSL to specific promoters and the circumstances in which the complex engages in regulating transcription are currently unknown. Here, we show that the NSL complex primarily targets active promoters and in particular housekeeping genes, at which it colocalizes with the chromatin remodeler NURF (nucleosome remodeling factor) and the histone methyltransferase Trithorax. However, only a subset of housekeeping genes associated with NSL are actually activated by it. Our analyses reveal that these NSL-activated promoters are depleted of certain insulator binding proteins and are enriched for the core promoter motif 'Ohler 5'. Based on these results, it is possible to predict whether the NSL complex is likely to regulate a particular promoter. We conclude that the regulatory capacity of the NSL complex is highly context-dependent. Activation by the NSL complex requires a particular promoter architecture defined by combinations of chromatin regulators and core promoter motifs. PMID- 22039100 TI - Solution structure and stability of the DNA undecamer duplexes containing oxanine mismatch. AB - Solution structures of DNA duplexes containing oxanine (Oxa, O) opposite a cytosine (O:C duplex) and opposite a thymine (O:T duplex) have been solved by the combined use of (1)H NMR and restrained molecular dynamics calculation. One mismatch pair was introduced into the center of the 11-mer duplex of [d(GTGACO(6)CACTG)/d(CAGTGX(17)GTCAC), X = C or T]. (1)H NMR chemical shifts and nuclear Overhauser enhancement (NOE) intensities indicate that both the duplexes adopt an overall right-handed B-type conformation. Exchangeable resonances of C(17) 4-amino proton of the O:C duplex and of T(17) imino proton of O:T duplex showed unusual chemical shifts, and disappeared with temperature increasing up to 30 degrees C, although the melting temperatures were >50 degrees C. The O:C mismatch takes a wobble geometry with positive shear parameter where the Oxa ring shifted toward the major groove and the paired C(17) toward the minor groove, while, in the O:T mismatch pair with the negative shear, the Oxa ring slightly shifted toward the minor groove and the paired T(17) toward the major groove. The Oxa mismatch pairs can be wobbled largely because of no hydrogen bond to the O1 position of the Oxa base, and may occupy positions in the strands that optimize the stacking with adjacent bases. PMID- 22039101 TI - Newt-omics: a comprehensive repository for omics data from the newt Notophthalmus viridescens. AB - Notophthalmus viridescens, a member of the salamander family is an excellent model organism to study regenerative processes due to its unique ability to replace lost appendages and to repair internal organs. Molecular insights into regenerative events have been severely hampered by the lack of genomic, transcriptomic and proteomic data, as well as an appropriate database to store such novel information. Here, we describe 'Newt-omics' (http://newt-omics.mpi bn.mpg.de), a database, which enables researchers to locate, retrieve and store data sets dedicated to the molecular characterization of newts. Newt-omics is a transcript-centred database, based on an Expressed Sequence Tag (EST) data set from the newt, covering ~50,000 Sanger sequenced transcripts and a set of high density microarray data, generated from regenerating hearts. Newt-omics also contains a large set of peptides identified by mass spectrometry, which was used to validate 13,810 ESTs as true protein coding. Newt-omics is open to implement additional high-throughput data sets without changing the database structure. Via a user-friendly interface Newt-omics allows access to a huge set of molecular data without the need for prior bioinformatical expertise. PMID- 22039102 TI - Characterization of flavins in roots of Fe-deficient strategy I plants, with a focus on Medicago truncatula. AB - The root accumulation and excretion of riboflavin (Rbfl) and Rbfl derivatives have been studied in the model legume species Medicago truncatula, grown in hydroponics in two different Fe deficiency conditions, with and without CaCO(3). Using high resolution mass spectrometry techniques coupled to liquid chromatography, three different flavin derivatives not previously reported in plants, putatively identified as 7-hydroxy-Rbfl, 7alpha-hydroxy-Rbfl and 7 carboxy-Rbfl, were found along with Rbfl in Fe-deficient M. truncatula roots. In the presence of CaCO(3) most of the flavins were accumulated in the roots, whereas in the absence of CaCO(3) there was partial export to the nutrient solution. The major flavins in roots and nutrient solution were Rbfl and 7 hydroxy-Rbfl, respectively. Flavins were located in the root cortex and epidermal cells, preferentially in a root region near the apex that also exhibited increased ferric chelate reductase (FCR) activity. Six out of 15 different species of horticultural interest showed root increases in both Rbfl (four of them also having Rbfl derivatives) and FCR. No significant correlation was found between Rbfl and either phosphoenolpyruvate carboxylase or FCR activities, whereas the latter two showed a good correlation between them. The possible roles of Rbfl and Rbfl derivatives in roots and nutrient solutions are discussed. Medicago truncatula is proposed as a model system for flavin studies. PMID- 22039103 TI - CYP716A subfamily members are multifunctional oxidases in triterpenoid biosynthesis. AB - Triterpenoids are a diverse group of secondary metabolites that are associated with a variety of biological activities. Oleanolic acid, ursolic acid and betulinic acid are common triterpenoids in plants with diverse biological activities, including antifungal, antibacterial, anti-human immunodeficiency virus (HIV) and/or antitumor activities. In the present study, using the gene co expression analysis tool of Medicago truncatula, we found a strong correlation between CYP716A12 and beta-amyrin synthase (bAS), which encodes the enzyme responsible for the initial cyclization of 2,3-oxidosqualene to beta-amyrin (the basic structural backbone of most triterpenoid saponins). Through an in vitro assay, we identified CYP716A12 as a beta-amyrin 28-oxidase able to modify beta amyrin to oleanolic acid (through erythrodiol and, possibly, oleanolic aldehyde). We also confirmed its activity in vivo, by expressing CYP716A12 in transgenic yeast that endogenously produce beta-amyrin. In addition, CYP716A12 was evaluated for its potential alpha-amyrin- and lupeol-oxidizing activities. Interestingly, CYP716A12 was able to generate ursolic acid (through uvaol and, possibly, ursolic aldehyde) and betulinic acid (through betulin). Hence, CYP716A12 was characterized as a multifunctional enzyme with beta-amyrin 28-oxidase, alpha amyrin 28-oxidase and lupeol 28-oxidase activities. We also identified homologs of CYP716A12 in grape (CYP716A15 and CYP716A17) that are involved in triterpenoid biosynthesis, which indicates the highly conserved functionality of the CYP716A subfamily among plants. These findings will be useful in the heterologous production of pharmacologically and industrially important triterpenoids, including oleanolic acid, ursolic acid and betulinic acid. PMID- 22039104 TI - Shotguns in the front line: phosphoproteomics in plants. AB - The emergence of 'shotgun proteomics' has paved the way for high-throughput proteome analysis, by which thousands of proteins can be identified simultaneously from complex samples. Although the shotgun approach has the potential to monitor many different post-translational modifications, further technological development is needed to enrich each post-translational 'modificome'. Large-scale in vivo phosphorylation site mapping, so-called shotgun phosphoproteomics, has become feasible in various organisms, including plants, owing to recent technological breakthroughs. Shotgun phosphoproteomics is not a mature technology, but progress has been rapid. In this review, we highlight the scope and limitations of current methods, and some key technological issues in this field. PMID- 22039105 TI - Autophagy in tobacco BY-2 cells cultured under sucrose starvation conditions: isolation of the autolysosome and its characterization. AB - Tobacco culture cells carry out a large-scale degradation of intracellular proteins in order to survive under sucrose starvation conditions. We have previously suggested that this bulk degradation of cellular proteins is performed by autophagy, where autolysosomes formed de novo act as the major lytic compartments. The digestion process in autolysosomes can be retarded by addition of the cysteine protease inhibitor E-64c to the culture medium, resulting in the accumulation of autolysosomes. In the present study, we have investigated several properties of autolysosomes in tobacco cells. Electron microscopy showed that the autolysosomes contain osmiophilic particles, some of which resemble partially degraded mitochondria. It also revealed the presence of two kinds of autolysosome precursor structures; one resembled the isolation membrane and the other the autophagosome of mammalian cells. Immunofluorescence microscopy showed that autolysosomes contain acid phosphatase, in accordance with cytochemical enzyme analyses by light and electron microscopy in a previous study. Autolysosomes isolated by cell fractionation on Percoll gradients showed the localization of acid phosphatase, vacuolar H(+)-ATPase and cysteine protease. These results show that starvation-induced autophagy in tobacco cells follows a macroautophagic-type response similar to that described for other eukaryotes. However, our results indicate that, although the plant vacuole is often described as being equivalent to the lysosome of the animal cell, a new low pH lytic compartment-the autolysosome-also contributes to proteolytic degradation when tobacco cells are subjected to sucrose deprivation. PMID- 22039106 TI - TB tendering could have a dramatic impact on rural practices. PMID- 22039107 TI - Plants 'unlikely to be the cause' of seasonal canine illness. PMID- 22039110 TI - Views sought on draft dog breeding rules in Northern Ireland. PMID- 22039111 TI - Engaging in the big society. PMID- 22039112 TI - Learning more about rabies. PMID- 22039113 TI - Apprenticeships as a route to higher education. PMID- 22039114 TI - Professionalism on display at BVNA congress. PMID- 22039115 TI - Towards a new vaccine for coccidiosis. PMID- 22039117 TI - Caring for the brains of young pups. PMID- 22039118 TI - Australian stringhalt in the UK. PMID- 22039119 TI - Bovine TB and wildlife control. PMID- 22039120 TI - The Cyt P450 enzyme CYP716A47 catalyzes the formation of protopanaxadiol from dammarenediol-II during ginsenoside biosynthesis in Panax ginseng. AB - Ginseng (Panax ginseng C.A. Meyer) is one of the most popular medicinal herbs and contains pharmacologically active components, ginsenosides, in its roots. Ginsenosides, a class of tetracyclic triterpene saponins, are thought to be synthesized from dammarenediol-II after hydroxylation by the Cyt P450 (CYP) enzyme and then glycosylation by glycosyltransferase (GT). However, no genes encoding the hydroxylation and glycosylation in ginsenoside biosynthesis have been identified. Here, we identify protopanaxadiol synthase, which is a CYP enzyme (CYP716A47), to be involved in the hydroxylation of dammarenediol-II at the C-12 position to yield protopanaxadiol. Nine putative full CYP sequences were isolated from the expressed sequence tags (ESTs) of methyl jasmonate (MeJA) treated adventitious ginseng roots. The CYP716A47 gene product was selected as the putative protopanaxadiol synthase because this gene was transcriptionally activated not only by MeJA treatment but also in transgenic ginseng that overexpresses squalene synthase and overproduces ginsenosides. In vitro enzymatic activity assays revealed that CYP716A47 catalyzed the oxidation of dammarenediol II to produce protopanaxadiol. Ectopic expression of CYP716A47 in recombinant WAT21 yeasts that were fed dammarenediol-II yielded protopanaxadiol. Furthermore, co-expression of the dammarenediol synthase gene (PgDDS) and CYP716A47 in yeast yielded protopanaxadiol without adding dammarenediol-II. The chemical structures of the protopanaxadiol products from dammarenediol-II were confirmed using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC/APCIMS). Thus, CYP716A47 is a dammarenediol 12-hydroxylase that produces protopanaxadiol from dammarenediol-II. PMID- 22039121 TI - Generation of transgenic rice lines with reduced contents of multiple potential allergens using a null mutant in combination with an RNA silencing method. AB - Rice seed proteins are known to be a causative antigen in some patients with food allergy, especially cereal allergy, with clinical symptoms such as eczema and dermatitis. The alpha-amylase/trypsin inhibitors (14-16 kDa), alpha-globulin (26 kDa) and beta-glyoxalase I (33 kDa) are regarded as major potential allergens of rice (Oryza sativa L.) seed based on specific recognition by serum IgE from allergy patients. In order to suppress the production of these major allergens in rice grains, a mutant in the 'Koshihikari' background lacking the 26 kDa allergen (GbN-1) was used as a host for RNA silencing. A binary vector harboring two RNA interference (RNAi) gene cassettes for suppression of 14-16 kDa and 33 kDa allergens driven by the 13 kDa and 10 kDa prolamin endosperm-specific promoters, respectively, was introduced into the GbN-1 genome by Agrobacterium-mediated transformation. In the most promising transgenic line, the content of the three potential allergens was remarkably reduced to a very faint level without a change in seed phenotype. IgE binding of 15 patients' sera to the transgenic rice seed mostly deficient in the three major allergens was on average only about 10% that of the control wild-type rice, suggesting that these three accounted for the great majority of rice seed causative allergens recognized by patients' IgE and that the sequential allergen deletion/reduction strategy works in the development of hypo-allergenic rice lines. PMID- 22039122 TI - Treadmill workstations: a worksite physical activity intervention in overweight and obese office workers. AB - PURPOSE: To determine if a treadmill-workstation (TMWS) increases physical activity (PA) and influences anthropometric, body composition, cardiovascular, and metabolic variables in overweight and obese office-workers. METHODS: Twelve (mean age= 46.2 +/- 9.2 years) overweight/obese sedentary office-workers (mean BMI= 33.9 +/- 5.0 kg.m-2) volunteered to participate in this 9-month study. After baseline measurements of postural allocation, steps per day, anthropometric variables, body composition, cardiovascular, and metabolic variables, TMWS were installed in the participants' offices for their use. Baseline measurements were repeated after 3 and 9 months. Comparisons of the outcome variables were made using repeated-measures ANOVAs or nonparametric Friedman's Rank Tests. RESULTS: Between baseline and 9 months, significant increases were seen in the median standing (146-203 min.day-1) and stepping time (52-90 min.day-1) and total steps/day (4351-7080 steps/day; P < .05). Correspondingly, the median time spent sitting/lying decreased (1238-1150 min.day-1; P < .05). Using the TMWS significantly reduced waist (by 5.5 cm) and hip circumference (by 4.8 cm), low density lipoproteins (LDL) (by 16 mg.dL-1), and total cholesterol (by 15 mg.dL-1) during the study (P < .05). CONCLUSION: The additional PA energy expenditure from using the TMWS favorably influenced waist and hip circumferences and lipid and metabolic profiles in overweight and obese office-workers. PMID- 22039123 TI - Evolution and devolution of national physical activity policy in Canada. AB - BACKGROUND: Low levels of physical activity (PA) and fitness have long been a government concern in Canada; however, more than half of adults are inactive. This article examines factors influencing policy development and implementation using Canadian PA policy as a case study. METHODS: Current and historical PA policy documents were amassed from a literature review, audit of government and non government websites and from requests to government officials in each jurisdiction directly responsible for PA. These were analyzed to determine policy content, results, barriers, and success factors. RESULTS: The national focus for PA policy in Canada has devolved to a multilevel system that meets most established criteria for successful strategies. Earlier PA targets have been met; however, the prevalence of PA decreased from 2005 to 2007. Annual per capita savings in health care associated with achieving the earlier target is estimated at $6.15 per capita, yet a fraction of that is directed to promoting PA. CONCLUSION: Evidenced-based strategies that address multiple policy agendas using sector-specific approaches are needed. Sustained high-level commitment is required; advocacy grounded in metrics and science is needed to increase the profile of the issue and increase the commitments to PA policies in Canada and internationally. PMID- 22039124 TI - Physical activity of children with and without long-term illness or disability. AB - BACKGROUND: We know very little about physical activity in children with long term illness or disability compared with those children without disabilities. Previous studies indicate low physical activity levels among all adolescents. METHODS: The sample consisted of Canadian (n = 2720) and Finnish pupils (n = 3459) approximately 13.5 and 15.5 years of age in general (mainstreamed) education. The study is a part of the Health Behavior in School-aged Children (HBSC) study. Nationally representative data were collected in 2002 using a standardized questionnaire. The moderate-to-vigorous intensity physical activity screening measure was used. RESULTS: Approximately one-fifth of the pupils in both countries had a long-term disability, illness or medical condition. In both countries boys and girls with a long-term illness or disability were equally physically inactive, and adolescents with a long-term illness or disability were as physically active as those without disabilities. CONCLUSIONS: There is no difference between young people with and without long-term illness/disability, and between boys and girls, in relation to their physical activity. However, all of them fall short of recommended guidelines. This indicates that promoting a physically active lifestyle should be of high priority in the lives of young people. PMID- 22039125 TI - Adolescent physical activity participation and motivational determinants across gender, age, and race. AB - BACKGROUND: Physical activity (PA) declines as adolescents get older, and the motivational determinants of PA warrant further investigation. The purposes of this study were to investigate the amount of physical and sedentary activity that adolescents participated in across age, gender, and race, and to investigate adolescents' attraction to PA and their perceived barriers and benefits across age, gender, and race. METHODS: High school students (N = 1163) aged between 13 and 16 years completed questionnaires on minutes and intensity of physical and sedentary activity, interests in physical activity, and perceived benefits and barriers to participating in PA. RESULTS: A series of multivariate analyses of variance were conducted and followed up with discriminant function analysis. PA participation decreased in older females. In addition, fun of physical exertion was a primary attraction to PA for males more than females. Body image as an expected outcome of participating in PA contributed most to gender differences. CONCLUSION: There is a need to determine why PA drops-off as females get older. Findings underscore the importance of structuring activities differently to sustain interest in male and female adolescents, and highlights motives of having a healthy body image, and making PA fun to enhance participation. PMID- 22039126 TI - A qualitative examination of factors related to the decrease in physical activity behavior in adolescent girls during the transition from primary to secondary school. AB - BACKGROUND: Quantitative research has suggested that the decline in physical activity levels for adolescent girls is most marked during the transition from primary school to secondary school yet understanding the contributing factors for this decline may be advanced through qualitative research methods to gain an individual perspective of the girls' school transition experience. METHODS: This study explored factors related to the decrease in physical activity behavior in 14 adolescent girls (mean age = 13.6 +/- 0.3 years) during the transition between primary and secondary school through the use of narrative interviews and interpretative phenomenological analysis. RESULTS: The findings suggested that a change in the environment was central to understanding the decline in physical activity levels since primary school. CONCLUSIONS: During secondary school, a positive environment can be created by ensuring a choice of activities in Physical Education lessons; allowing a girls-only environment, to reduce the focus on competence and competition, and recognizing the importance of social support. These could enhance self-perceptions, reduce self-presentational concerns, increase enjoyment, and subsequently reduce the decrease in physical activity behavior during this key transitional period. PMID- 22039127 TI - The impacts of building a greenway on proximate residents' physical activity. AB - BACKGROUND: A significant association has been identified between physical activity and proximity to greenways. However, residents more likely to be active may have selected to live near existing greenways. The purpose of this study was to determine whether development of a new greenway has the potential to increase activity levels of existing, proximate residents. METHODS: In 2008, survey data were collected before and after 5 miles of greenway were added to an existing greenway. RESULTS: When comparing residents living nearest (<= .50 miles) the new greenway section with those living further (.51-1.0 miles), days spent walking and participating in moderate physical activity increased. Despite mean increases, no significant interactions were detected. CONCLUSIONS: Although evidence is inconclusive, apparent increases in walking and moderate activity suggest development of a greenway proximate to residents' homes is likely to have a positive effect on participation levels. Additional research is needed to address article limitations. PMID- 22039128 TI - Perceived walkability, social support, age, native language, and vehicle access as correlates of physical activity: a cross-sectional study of low-socioeconomic status, ethnic, minority women. AB - BACKGROUND: The role of social-environmental factors in physical activity (PA) within lower income and ethnic minority populations is understudied. This study explored correlates of age-related PA and perceived walkability (PW). METHODS: Cross-sectional data (N = 401 women; >=18 y) were collected within the Jane-Finch community in Toronto, Ontario using questionnaires. Generalized additive models, an extension to multiple regression, were used to estimate effect sizes and standard errors. RESULTS: Significant interactions between native language and car access (CA) were observed in PA variation across the lifespan. Individuals were evenly distributed across 4 comparison groups: 29.2% English-NoCA, 24.1% English-CA, 20.7% Non-English-NoCA, and 26.0% NonEnglish-CA. Risk of sedentariness increased with age for native English speakers > 50 years, but appears unaffected by age for other groups. English speakers without CA < 60 years appear least likely to be sedentary, followed by English speakers with CA. In general, an active individual at the 75th percentile of social support for exercise would have 1.62 (CI: 1.22-2.17) times the MET-Hours of PA than an active individual at the 25th percentile of SSE. CONCLUSIONS: English language facility and car access moderate relationships of social-environmental factors and PA. Further investigation is required to better understand correlates of PA for women in this demographic. PMID- 22039129 TI - Validation of the SOPLAY direct observation tool with an accelerometry-based physical activity monitor. AB - BACKGROUND: The System for Observing Play and Leisure Activities (SOPLAY) is a direct observation instrument designed to assess group physical activity and environmental contexts. The purpose of this study was to test the convergent validity of the SOPLAY using temporally matched data from an accelerometry-based activity monitor. METHODS: Accelerometry-based physical activity data were obtained from 160 elementary school children from 9 after-school activity programs. SOPLAY coding was used to directly observe physical activity during these sessions. Analyses evaluated agreement between the monitored and observed physical activity behavior by comparing the percent of youth engaging in physical activity with the 2 assessments. RESULTS: Agreement varied widely depending on the way the SOPLAY codes were interpreted. Estimates from SOPLAY were significantly higher than accelerometer PA levels when codes of walking and vigorous were used (in combination) to reflect participation in moderate to vigorous PA (MVPA). Estimates were similar when only SOPLAY codes of vigorous were used to define MVPA (Difference = 1.33 +/- 22.06%). CONCLUSIONS: SOPLAY codes of walking corresponded well with estimates of Light intensity PA. Observations provide valid indicators of MVPA if coding is based on the percentage of youth classified as "vigorous." PMID- 22039130 TI - How much observation is enough? Refining the administration of SOPARC. AB - BACKGROUND: The Systematic Observation of Play and Recreation in Communities (SOPARC) was designed to estimate the number and characteristics of people using neighborhood parks by assessing them 4 times/day, 7 days/week. We tested whether this schedule was adequate and determined the minimum number of observations necessary to provide a robust estimate of park user characteristics and their physical activity levels. METHODS: We conducted observations every hour for 14 hours per day during 1 summer and 1 autumn week in 10 urban neighborhood parks: 2 each in Los Angeles, CA; Albuquerque, NM; Columbus, OH; Durham, NC; and Philadelphia, PA. We counted park users by gender, age group, apparent race/ethnicity, and activity level. We used a standardized Cronbach's alpha and intraclass correlation coefficients to test the reliability of using fewer observations. RESULTS: We observed 76,632 individuals, an average of 547/park/day (range 155-786). Interobserver reliability ranged from 0.80 to 0.99. Obtaining a robust estimate of park user characteristics and their physical activity required a schedule of 4 days/week, 4 times/day. CONCLUSION: An abbreviated schedule of SOPARC was sufficient for estimating park use, park user characteristics, and physical activity. Applying these observation methods can augment physical activity surveillance. PMID- 22039131 TI - Accuracy of multisensor activity monitors in normal versus high BMI African American children. AB - BACKGROUND: Overweight children show different movement patterns during walking than normal-weight children, suggesting the accuracy of multisensory activity monitors may differ in these groups. METHODS: Eleven normal and 15 high BMI African American children walked at 2, 4, 5, and 6 km/h on a treadmill wearing the Intelligent Device for Energy Expenditure and Activity (IDEEA) and SenseWear (SW). Accuracy was determined using indirect calorimetry and manually counted steps as references. RESULTS: For IDEEA, no significant differences in accuracy were observed between BMI groups for energy expenditure (EE), but differences were significant by speed (+15% at 2 km/h to -10% at 6 km/h). For SW, EE accuracy was significantly different for high (+21%) versus normal BMI girls (-13%) at 2 km/h. For high BMI girls, EE was overestimated at low speed and underestimated at higher speeds. Underestimations in steps did not differ by BMI group at 4 to 6 km/h, but were significantly larger at 2 km/h than at the other speeds for all groups with IDEEA, and for normal BMI children with SW. CONCLUSIONS: Similar accuracies during walking may be expected in normal and overweight children using IDEEA and SW. Both monitors showed small errors for steps provided speed exceeded 2 km/h. PMID- 22039132 TI - Physical inactivity in Nigerian young adults: prevalence and socio-demographic correlates. AB - BACKGROUND: This study assessed the prevalence of physical inactivity and the influence of sociodemographic variables on physical activity categories, highlighting the correlates of physical inactivity in Nigerian young adults. METHODS: A representative sample of young adults age 16 to 39 years (n = 1006) from a Nigerian University were categorized using the International Physical Activity Questionnaire as physically inactive, moderately active, and highly active. Prevalence rates were computed for the activity categories and the independent associations of sociodemographic correlates on each category were determined using the multinomial logistic regression. RESULTS: Physical inactivity prevalence was 41%. More likely to be inactive were females (OR = 1.93; CI: 1.49-2.49), those of Hausa ethnicity (OR = 2.29; CI: 1.08-5.84), having BMI > 30 kg/m2 (OR = 2.88; CI: 1.16-7.17), and those whose parents' annual income was < 180,000 NAIRA (OR = 1.69; CI: 1.04-2.95). Less likely to be moderately active were females (OR = 0.71; CI: 0.61-0.95), those with BMI between 25.0 to 29.9 kg/m2 (OR = 0.46; CI: 0.23-0.92), and those of Hausa ethnicity (OR = 0.17; CI: 0.04-0.74). CONCLUSION: Important sociodemographic variables that can contribute to the preliminary analysis of correlates of physical inactivity among Nigerian young adults were identified. PMID- 22039133 TI - Pedometer variance in adults with Down syndrome during free walking: a generalizability study. AB - BACKGROUND: Pedometers are a common instrument used to measure walking activity, yet reliability evidence in disability populations, particularly Down syndrome (DS), has received little attention. There may be systematic and random sources of error that could influence reliability under natural walking conditions. The purpose of this study was to examine the sources of variance and estimate reliability coefficients of spring-levered (SL) and piezoelectric (PZ) pedometers for adults with DS during a free-walking bout. METHODS: Seventeen adults with DS and 23 adults without a disability walked continuously for a 20-minute period wearing 2 types of pedometers, SL and PZ. Step counts were analyzed using Generalizability theory to partition and quantify variance components and calculate reliability coefficients. RESULTS: The largest variance component was due to individual participant differences. Adults with DS demonstrated greater intraindividual variability, but also had relatively low proportions of residual variance, or unexplained error. The SL pedometer showed problems with interunit variance while the PZ pedometer demonstrated little systematic error. Reliability coefficients were consistently higher for the PZ pedometer. CONCLUSIONS: This study found minimal systematic error and moderate reliability evidence for the PZ pedometer. This type of pedometer may be used in future research for adults with DS. PMID- 22039134 TI - Factors associated with adherence to an accelerometer protocol in older adults. AB - BACKGROUND: Adherence to protocols of accelerometer use by participants of research studies is crucial to ensure the most accurate measure of their physical activity. METHODS: We used data from a study of 201 individuals 65 years of age and older to examine whether aging effects on physical and cognitive health limit the ability of an older adult to be adherent to an accelerometer protocol. RESULTS: A comparison of participants who met the adherent person criteria with those who did not showed that the percentage of participants whose income is $20,000 or greater, the percentage of participants who reported white race, and the mean number of school grades completed were significantly different between the 2 groups. Logistic regression analyses showed that the best multivariate model to predict being a valid person included Instrumental Activities of Daily Living score, while the best multivariate model to predict being an adherent person included Modified Guralnik Lower Body Score and Mini-Mental State Examination Score. CONCLUSIONS: This study found that certain measures of physical and cognitive functioning were the best predictors of adherence to an accelerometer protocol among older adults. PMID- 22039135 TI - Cycling to school and cardiovascular risk factors: a longitudinal study. AB - BACKGROUND: Cycling to school may potentially increase physical activity level in sedentary children. Transport to school occur twice a day and could improve cardiovascular health in children. Commuter cycling is associated with lower mortality and cardiovascular disease rate in adults, but limited evidence exists in children. METHODS: Participants were 334 children (age 9.7 +/- 0.5 years) who were followed up 6 years later. Mode of travel to school was investigated by questionnaire. Cardiovascular (CVD) risk factors were compared by mode of travel to school both at baseline and at follow up and for subjects who changed mode of transportation. No difference was found between walkers and passive travelers, and these groups were merged in the analysis. RESULTS: A consistent pattern of better CVD risk factor profile in commuter cyclists compared with children using other means of transport was found. Participants, who did not cycle to school at baseline, and who had changed to cycling at follow up, were fitter, had better cholesterol/HDL ratio, better glucose metabolism, and a lower composite CVD risk factor score than those who did not cycle at either time point. CONCLUSION: Cycling to school may contribute to a better cardiovascular risk factor profile in young people. PMID- 22039136 TI - The association between the type, context, and levels of physical activity amongst adolescents. AB - BACKGROUND: Little is known about how the type and context of physical activity behaviors varies among adolescents with differing activity levels. The aim of this study was to assess differences in the type and context of physical activity behaviors in adolescents by level of objectively measured physical activity. METHODS: Cross-sectional analysis of 2728 adolescents (1299 males, 1429 females) participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). The mean (SD) age was 13.8 (+0.1) years. Physical activity was measured using an Actigraph over 7 days. Adolescents were categorized into tertiles of activity (less, moderately, highly active) using counts/min and min/d of moderate-to vigorous activity (MVPA). Activity type was reported using the Previous Day Physical Activity Recall (PDPAR). Differences in the type and context of activity by activity level were analyzed using Chi squared. RESULTS: Highly active boys reported more job, outside, and sports activities on school days (P < .05), and more sports activities on nonschool days (P < .05). Highly active girls reported more outside activities on school days (P < .05). CONCLUSIONS: Identifying the type and context of physical activity behaviors associated with more active adolescents, can help inform policy and physical activity interventions aimed at increasing activity levels in adolescents. PMID- 22039137 TI - Clinical research and healthcare outcomes. PMID- 22039138 TI - How may clinical research improve healthcare outcomes? AB - Healthcare outcomes such as overall survival or quality of life are the end results of a complex interaction between the patient, treatment and the healthcare system. Research may identify superior interventions but their dissemination and changing the behaviour of healthcare providers is challenging. Demonstrating and measuring the benefits of clinical research on healthcare outcomes is an important issue but there is remarkably little empiric work to date in this area. In this chapter we explore benefits that may arise in healthcare from contributing to clinical research, and consider the mechanisms which may be relevant. Improvements in infrastructure, the processes of care and workforces are important. Complex adaptive systems theory provides a framework for considering the many feedback loops that relate research, health outcomes and the behaviour of healthcare providers. Given the costs of research, additional studies to examine the impact of research on healthcare outcomes and to explore the mechanisms are justified and highly desirable. PMID- 22039139 TI - Clinical research in epithelial ovarian cancer and patients' outcome. AB - We evaluated the relationship between the outcome of newly diagnosed ovarian cancer patients treated in 1123 German gynecology departments in 2001, and their participation in clinical trials through two German cooperative study groups. In addition, we evaluated other potential factors predicting outcome including hospital volume. The analysis was based on 476 patients from 165 hospitals and 3 year follow-up. Patients treated in study hospitals had a higher chance of receiving treatment according to national guidelines. This included a higher chance of receiving optimal staging in early stage disease and of receiving the recommended combination of surgical debulking and combination chemotherapy in advanced disease. On multivariable Cox model analysis, overall survival was significantly worse in patients treated in non-study hospitals. PMID- 22039140 TI - The impact of the process of clinical research on health service outcomes. PMID- 22039141 TI - Clinical trials of cancer screening in the developing world and their impact on cancer healthcare. AB - Several research and training initiatives were organized by the International Agency for Research on Cancer (IARC) in collaboration with national institutions in countries such as Angola, Brazil, Burkina Faso, China, Republic of Congo, Guinea, India, Mali, Mauritania, Nepal, Niger, Peru, Tanzania and Thailand among others, to address feasible and effective means of early detection and prevention of cervical, breast and oral cancers. The impact of these activities, that involved over 600 000 participants and more than 1200 healthcare personnel trained on strengthening the local health services in terms of infrastructure, human resources and service delivery aspects in host countries and other regions, is addressed here. These studies, inbuilt in appropriate health services platforms, have resulted in the development and sustenance of several continuing point of care services of screening and treatment in most host countries, particularly in sub-Saharan Africa, and have catalysed regional early detection programmes in India, China and Thailand. The IARC collaborative studies have evolved into major focal points of training and extending services in many countries. The large evidence base, resulting from ours and other studies is likely, in due course, to facilitate much wider scaling up of screening and treatment services through organised programmes. PMID- 22039142 TI - Research-intensive cancer care in the NHS in the UK. AB - In the late 1990 s, in response to poor national cancer survival figures, government monies were invested to enhance recruitment to clinical cancer research. Commencing with England in 2001 and then rolling out across all four countries, a network of clinical cancer research infrastructure was created, the new staff being linked to existing clinical care structures including multi disciplinary teams. In parallel, a UK-wide co-ordination of cancer research funders driven by the 'virtual' National Cancer Research Institute, combined to create a 'whole-system approach' linking research funders, researchers and NHS clinicians all working to the same ends. Over the next 10 years, recruitment to clinical trials and other well-designed studies, increased 4-fold, reaching 17% of the incident cancer population, the highest national rate world-wide. The additional resources led to more studies opened, and more patients recruited across the country, for all types of cancers and irrespective of additional clinical research staff in some hospitals. In 2006, a co-ordinated decision was made to increasingly focus on randomized trials, leading to increased recruitment, without any fall-off in accrual to non-randomized and observational studies. The National Cancer Research Network has supported large successful trials which are changing clinical practice in many cancers. PMID- 22039143 TI - Extending the clinical research network approach to all of healthcare. AB - The development of Clinical Research Networks (CRN) has been central to the work conducted by Health Departments and research funders to promote and support clinical research within the NHS in the UK. In England, the National Institute for Health Research has supported the delivery of clinical research within the NHS primarily through CRN. CRN provide the essential infrastructure within the NHS for the set up and delivery of clinical research within a high-quality peer reviewed portfolio of studies. The success of the National Cancer Research Network is summarized in Chapter 5. In this chapter progress in five other topics, and more recently in primary care and comprehensively across the NHS, is summarized. In each of the 'topic-specific' networks (Dementias and Neurodegenerative Diseases, Diabetes, Medicines for Children, Mental Health, Stroke) there has been a rapid and substantial increase in portfolios and in the recruitment of patients into studies in these portfolios. The processes and the key success factors are described. The CRN have worked to support research supported by pharmaceutical, biotechnology and medical device companies and there has been substantial progress in improving the speed, cost and delivery of these 'industry' studies. In particular, work to support the increased speed of set up and delivery of industry studies, and to embed this firmly in the NHS, was explored in the North West of England in an Exemplar Programme which showed substantial reductions in study set-up times and improved recruitment into studies and showed how healthcare (NHS) organizations can overcome delays in set up times when they actively manage the process. Seven out of 20 international studies reported that the first patient to be entered anywhere in the world was from the UK. In addition, the CRN have supported research management and governance, workforce development and clinical trials unit collaboration and coordination. International peer reviews of all of the CRN have been positive and resulted in the continuation of the system for a further 5 years in all cases. PMID- 22039144 TI - A European perspective--the European clinical research infrastructures network. AB - Evaluating research outcomes requires multinational cooperation in clinical research for optimization of treatment strategies and comparative effectiveness research, leading to evidence-based practice and healthcare cost containment. The European Clinical Research Infrastructures Network (ECRIN) is a distributed ESFRI (European Strategy Forum on Research Infrastructures) roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients, and unlocking latent scientific potential. Servicing multinational trials started during its preparatory phase, and ECRIN will now apply for an ERIC (European Research Infrastructures Consortium) status by 2011. By creating a single area for clinical research in Europe, this achievement will contribute to the implementation of the Europe flagship initiative 2020 'Innovation Union', whose objectives include defragmentation of the research and education capacity, tackling the major societal challenges starting with the area of healthy ageing, and removing barriers to bring ideas to the market. PMID- 22039145 TI - The impact of the process of clinical research on health service outcomes. AB - Chapter 1 introduces the key questions and context for the work described in the supplement, on the impact of the process of clinical research on healthcare outcomes. The distinction between the influence of research activity on the outcomes for individual patients involved in clinical trials and other well designed studies when compared to similar individuals cared for within similar healthcare institutions are considered. The evidence is reviewed and broadly the conclusion is that there is little evidence to support the hypothesis that individuals included in randomized trials do better than individuals with the same clinical characteristics in such trials within the same institution. However, the more important question of the influence of research activity on the outcomes of healthcare institutions is identified and clarified. There are less research data which address this question and it is harder to study. However, the existing data are encouraging and suggest that the hypothesis that research- intensive healthcare institutions provide improved outcomes is worthy of further study. There is a pressing need for additional high-quality, methodologically robust studies of this question. PMID- 22039146 TI - The impact of HIV research on health outcome and healthcare policy. AB - Human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) have shown an almost unique linkage between biomedical research and improved healthcare outcomes. A transformation has been seen between 1981 when AIDS was a rapidly fatal condition, to the present dramatic survival prolongation. HIV infection is a chronic illness requiring ongoing modern therapy. Parallels and interactions between HIV research and cancer research are close. The ability of novel therapies to suppress HIV replication and restore host immunity has decreased the incidence and progression of cancers in HIV patients. The rapid application of new knowledge to patient care and health policy in HIV has key lessons for other disease areas. Patient and Public Involvement has been influential in research activity and funding. The availability of laboratory markers of disease has been central to the successful application of novel HIV therapies. Active development and management of cooperative large-scale clinical trials supported by advocacy groups was influential. HIV investigators have been at the forefront of identifying cost effective treatments that can be widely applied. The science, clinical research and political response to the HIV epidemic offer a model generalizable to other serious diseases. Opportunities to share the experiences and lessons learned from HIV should be sought, particularly in the cancer research community. PMID- 22039147 TI - Patient and public involvement. AB - The involvement of patients and the public in the development of clinical research initiatives in the UK has been central and is increasing. Whilst initially developed in relation to cancer research and cancer care, this activity has now generalized to all of healthcare research particularly through organizations such as INVOLVE (www.invo.org.uk). Patients and Public Involvement (PPI) has been evaluated and shown to be established across the NHS in the UK. The National Institute for Health Research in England has made PPI central in its development. More recently evidence is accumulating that PPI has significant impact on the quality and delivery of clinical research in healthcare but more work on the evaluation of its impact is required. PMID- 22039148 TI - Future research and methodological approaches. AB - This supplement has explored the evidence for benefits from the participation of healthcare institutions and their patients in clinical research. The questions have been clarified. There is some encouragement that research active healthcare institutions may deliver improved outcomes compared to less research-active or research-inactive institutions but there is a pressing need for further research. In this chapter we explore the methodological challenges to evaluating the impact of the process of clinical research on hospitals and other healthcare organizations. The postulated mechanisms by which benefits may be accrued are important drivers of the types of research needed and these are emphasized. Study designs are explored including formal randomized trials, the stepped wedge randomized design, approaches to the design and analysis of observational studies particularly to examine whether a temporal or spatial relationship exists between changes in research activity and patients' outcomes. It is acknowledged that in most future studies the data available will be cross-sectional and observational, and such studies are susceptible to many types of bias. The importance of identifying and addressing such biases in multivariate analysis is discussed and examples of successful studies are given. PMID- 22039150 TI - Strand antagonism in RNAi: an explanation of differences in potency between intracellularly expressed siRNA and shRNA. AB - Strategies to regulate gene function frequently use small interfering RNAs (siRNAs) that can be made from their shRNA precursors via Dicer. However, when the duplex components of these siRNA effectors are expressed from their respective coding genes, the RNA interference (RNAi) activity is much reduced. Here, we explored the mechanisms of action of shRNA and siRNA and found the expressed siRNA, in contrast to short hairpin RNA (shRNA), exhibits strong strand antagonism, with the sense RNA negatively and unexpectedly regulating RNAi. Therefore, we altered the relative levels of strands of siRNA duplexes during their expression, increasing the level of the antisense component, reducing the level of the sense component, or both and, in this way we were able to enhance the potency of the siRNA. Such vector-delivered siRNA attacked its target effectively. These findings provide new insight into RNAi and, in particular, they demonstrate that strand antagonism is responsible for making siRNA far less potent than shRNA. PMID- 22039151 TI - ALFRED: an allele frequency resource for research and teaching. AB - ALFRED (http://alfred.med.yale.edu) is a free, web accessible, curated compilation of allele frequency data on DNA sequence polymorphisms in anthropologically defined human populations. Currently, ALFRED has allele frequency tables on over 663,400 polymorphic sites; 170 of them have frequency tables for more than 100 different population samples. In ALFRED, a population may have multiple samples with each 'sample' consisting of many individuals on which an allele frequency is based. There are 3566 population samples from 710 different populations with allele frequency tables on at least one polymorphism. Fifty of those population samples have allele frequency data for over 650,000 polymorphisms. Records also have active links to relevant resources (dbSNP, PharmGKB, OMIM, Ethnologue, etc.). The flexible search options and data display and download capabilities available through the web interface allow easy access to the large quantity of high-quality data in ALFRED. PMID- 22039152 TI - ProGlycProt: a repository of experimentally characterized prokaryotic glycoproteins. AB - ProGlycProt (http://www.proglycprot.org/) is an open access, manually curated, comprehensive repository of bacterial and archaeal glycoproteins with at least one experimentally validated glycosite (glycosylated residue). To facilitate maximum information at one point, the database is arranged under two sections: (i) ProCGP-the main data section consisting of 95 entries with experimentally characterized glycosites and (ii) ProUGP-a supplementary data section containing 245 entries with experimentally identified glycosylation but uncharacterized glycosites. Every entry in the database is fully cross-referenced and enriched with available published information about source organism, coding gene, protein, glycosites, glycosylation type, attached glycan, associated oligosaccharyl/glycosyl transferases (OSTs/GTs), supporting references, and applicable additional information. Interestingly, ProGlycProt contains as many as 174 entries for which information is unavailable or the characterized glycosites are unannotated in Swiss-Prot release 2011_07. The website supports a dedicated structure gallery of homology models and crystal structures of characterized glycoproteins in addition to two new tools developed in view of emerging information about prokaryotic sequons (conserved sequences of amino acids around glycosites) that are never or rarely seen in eukaryotic glycoproteins. ProGlycProt provides an extensive compilation of experimentally identified glycosites (334) and glycoproteins (340) of prokaryotes that could serve as an information resource for research and technology applications in glycobiology. PMID- 22039153 TI - PomBase: a comprehensive online resource for fission yeast. AB - PomBase (www.pombase.org) is a new model organism database established to provide access to comprehensive, accurate, and up-to-date molecular data and biological information for the fission yeast Schizosaccharomyces pombe to effectively support both exploratory and hypothesis-driven research. PomBase encompasses annotation of genomic sequence and features, comprehensive manual literature curation and genome-wide data sets, and supports sophisticated user-defined queries. The implementation of PomBase integrates a Chado relational database that houses manually curated data with Ensembl software that supports sequence based annotation and web access. PomBase will provide user-friendly tools to promote curation by experts within the fission yeast community. This will make a key contribution to shaping its content and ensuring its comprehensiveness and long-term relevance. PMID- 22039154 TI - The SARS-coronavirus nsp7+nsp8 complex is a unique multimeric RNA polymerase capable of both de novo initiation and primer extension. AB - Uniquely among RNA viruses, replication of the ~30-kb SARS-coronavirus genome is believed to involve two RNA-dependent RNA polymerase (RdRp) activities. The first is primer-dependent and associated with the 106-kDa non-structural protein 12 (nsp12), whereas the second is catalysed by the 22-kDa nsp8. This latter enzyme is capable of de novo initiation and has been proposed to operate as a primase. Interestingly, this protein has only been crystallized together with the 10-kDa nsp7, forming a hexadecameric, dsRNA-encircling ring structure [i.e. nsp(7+8), consisting of 8 copies of both nsps]. To better understand the implications of these structural characteristics for nsp8-driven RNA synthesis, we studied the prerequisites for the formation of the nsp(7+8) complex and its polymerase activity. We found that in particular the exposure of nsp8's natural N-terminal residue was paramount for both the protein's ability to associate with nsp7 and for boosting its RdRp activity. Moreover, this 'improved' recombinant nsp8 was capable of extending primed RNA templates, a property that had gone unnoticed thus far. The latter activity is, however, ~20-fold weaker than that of the primer-dependent nsp12-RdRp at equal monomer concentrations. Finally, site directed mutagenesis of conserved D/ExD/E motifs was employed to identify residues crucial for nsp(7+8) RdRp activity. PMID- 22039155 TI - Highly parallel oligonucleotide purification and functionalization using reversible chemistry. AB - We have developed a cost-effective, highly parallel method for purification and functionalization of 5'-labeled oligonucleotides. The approach is based on 5' hexa-His phase tag purification, followed by exchange of the hexa-His tag for a functional group using reversible reaction chemistry. These methods are suitable for large-scale (micromole to millimole) production of oligonucleotides and are amenable to highly parallel processing of many oligonucleotides individually or in high complexity pools. Examples of the preparation of 5'-biotin, 95-mer, oligonucleotide pools of >40K complexity at micromole scale are shown. These pools are prepared in up to ~16% yield and 90-99% purity. Approaches for using this method in other applications are also discussed. PMID- 22039149 TI - The blood-testis barrier and its implications for male contraception. AB - The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium into the basal and the apical (adluminal) compartments. Meiosis I and II, spermiogenesis, and spermiation all take place in a specialized microenvironment behind the BTB in the apical compartment, but spermatogonial renewal and differentiation and cell cycle progression up to the preleptotene spermatocyte stage take place outside of the BTB in the basal compartment of the epithelium. However, the BTB is not a static ultrastructure. Instead, it undergoes extensive restructuring during the seminiferous epithelial cycle of spermatogenesis at stage VIII to allow the transit of preleptotene spermatocytes at the BTB. Yet the immunological barrier conferred by the BTB cannot be compromised, even transiently, during the epithelial cycle to avoid the production of antibodies against meiotic and postmeiotic germ cells. Studies have demonstrated that some unlikely partners, namely adhesion protein complexes (e.g., occludin-ZO-1, N-cadherin-beta-catenin, claudin-5-ZO-1), steroids (e.g., testosterone, estradiol-17beta), nonreceptor protein kinases (e.g., focal adhesion kinase, c-Src, c-Yes), polarity proteins (e.g., PAR6, Cdc42, 14-3-3), endocytic vesicle proteins (e.g., clathrin, caveolin, dynamin 2), and actin regulatory proteins (e.g., Eps8, Arp2/3 complex), are working together, apparently under the overall influence of cytokines (e.g., transforming growth factor-beta3, tumor necrosis factor-alpha, interleukin 1alpha). In short, a "new" BTB is created behind spermatocytes in transit while the "old" BTB above transiting cells undergoes timely degeneration, so that the immunological barrier can be maintained while spermatocytes are traversing the BTB. We also discuss recent findings regarding the molecular mechanisms by which environmental toxicants (e.g., cadmium, bisphenol A) induce testicular injury via their initial actions at the BTB to elicit subsequent damage to germ-cell adhesion, thereby leading to germ-cell loss, reduced sperm count, and male infertility or subfertility. Moreover, we also critically evaluate findings in the field regarding studies on drug transporters in the testis and discuss how these influx and efflux pumps regulate the entry of potential nonhormonal male contraceptives to the apical compartment to exert their effects. Collectively, these findings illustrate multiple potential targets are present at the BTB for innovative contraceptive development and for better delivery of drugs to alleviate toxicant-induced reproductive dysfunction in men. PMID- 22039156 TI - Unexplained hemolytic anemia with multiorgan failure. PMID- 22039157 TI - Cadmium concentrations. PMID- 22039158 TI - Cadmium exposure. PMID- 22039159 TI - What is wrong with this picture? PMID- 22039163 TI - CELLPEDIA: a repository for human cell information for cell studies and differentiation analyses. AB - CELLPEDIA is a repository database for current knowledge about human cells. It contains various types of information, such as cell morphologies, gene expression and literature references. The major role of CELLPEDIA is to provide a digital dictionary of human cells for the biomedical field, including support for the characterization of artificially generated cells in regenerative medicine. CELLPEDIA features (i) its own cell classification scheme, in which whole human cells are classified by their physical locations in addition to conventional taxonomy; and (ii) cell differentiation pathways compiled from biomedical textbooks and journal papers. Currently, human differentiated cells and stem cells are classified into 2260 and 66 cell taxonomy keys, respectively, from which 934 parent-child relationships reported in cell differentiation or transdifferentiation pathways are retrievable. As far as we know, this is the first attempt to develop a digital cell bank to function as a public resource for the accumulation of current knowledge about human cells. The CELLPEDIA homepage is freely accessible except for the data submission pages that require authentication (please send a password request to cell-info@cbrc.jp). Database URL: http://cellpedia.cbrc.jp/ PMID- 22039164 TI - Paracetamol and cyclooxygenase inhibition: is there a cause for concern? AB - Paracetamol is recommended as first-line therapy for pain associated with osteoarthrosis and is one of the most widely used over-the-counter analgesic drugs worldwide. Despite its extensive use, its mode of action is still unclear. Although it is commonly stated that paracetamol acts centrally, recent data imply an inhibitory effect on the activity of peripheral prostaglandin-synthesising cyclooxygenase enzymes. In this context paracetamol has been suggested to inhibit both isoforms in tissues with low levels of peroxide by reducing the higher oxidation state of cyclooxygenase enzymes. Two recent studies have also demonstrated a preferential cyclooxygenase 2 (COX-2) inhibition by paracetamol under different clinically relevant conditions. This review attempts to relate data on paracetamol's inhibitory action on peripheral cyclooxygenase enzymes to the published literature on its anti-inflammatory action and its hitherto underestimated side-effects elicited by cyclooxygenase inhibition. As a result, a pronounced COX-2 inhibition by paracetamol is expected to occur in the endothelium, possibly explaining its cardiovascular risk in epidemiological studies. A careful analysis of paracetamol's cardiovascular side-effects in randomised studies is therefore strongly advised. On the basis of epidemiological data showing an increased gastrointestinal risk of paracetamol at high doses or when co-administered with classic cyclooxygenase inhibitors, paracetamol's long term gastrointestinal impact should be investigated in randomised trials. Finally, paracetamol's fast elimination and consequently short-lived COX-2 inhibition, which requires repetitive dosing, should be definitely considered to avoid overdosage leading to hepatotoxicity. PMID- 22039165 TI - Serum markers associated with clinical improvement in patients with ankylosing spondylitis treated with golimumab. AB - OBJECTIVE: Identify serum biomarkers modulated by golimumab treatment and associated with clinical response in patients with ankylosing spondylitis (AS). METHODS: Sera were collected at weeks 0, 4 and 14 from 100 patients with active AS in the GO-RAISE study. Patients were randomly assigned subcutaneous injections of placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks. Samples were tested for select inflammatory, bone and cartilage markers, and protein profiling was also performed. RESULTS: Golimumab treatment resulted in significant decreases in several serum proteins at weeks 4 and 14 compared with placebo. Patients who achieved clinical response at week 14, as assessed by a >=20% improvement in the Assessment in SpondyloArthitis international Society response criteria (ASAS 20), demonstrated a distinct biomarker profile with lower levels of acute phase reactants and inflammatory biomarkers compared with patients who did not. Notably, combinations of two or three biomarkers assessed at baseline were predictive of various clinical outcomes (ASAS 20, Bath ankylosing spondylitis disease activity index 50 or Bath ankylosing spondylitis functional index) using a logistic regression analysis, and the overall predictive values for these combined biomarkers were greater than observed for C-reactive protein (CRP) alone. CONCLUSION: Golimumab modulated acute phase reactants and inflammatory markers in patients with active AS. Specific combinations of biomarkers at baseline demonstrated a stronger prediction for clinical efficacy than CRP alone. These data provide insights into the mechanism of golimumab on inflammatory processes driving AS pathology, and may have utility in managing the treatment of patients with AS. PMID- 22039166 TI - Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response. AB - Following a greater understanding of the pathogenesis of rheumatoid arthritis (RA), the treatment of this chronic disease has improved with the availability of biological agents targeting key molecules. Despite this, initial treatment produces an inadequate response in many patients and guidance on the optimal treatment for these patients is needed. Research in specific patient populations aims to define predictive biomarkers of response to identify those patients most likely to benefit from treatment with specific agents. Although there have been conflicting results from studies of various genetic markers, single nucleotide polymorphisms in the tumour necrosis factor (TNF) -308 promoter region may play a role in response to specific TNF inhibitors. Microarray analysis of mRNA expression levels has identified unique sets of genes with differentially regulated expression in responders compared with non-responders to the TNF inhibitor infliximab. Of the various protein biomarkers studied, rheumatoid factor and/or anticitrullinated protein autoantibodies may have a future role in predicting response or guiding the order in which to use biological agents. Further research is needed with larger, well-designed studies to clarify the current understanding on the role of biomarkers in predicting treatment response in RA to help guide clinical decision-making. Individualised treatment has the potential to improve the therapeutic outcomes for patients. PMID- 22039167 TI - Level of agreement of the 1987 ACR and 2010 ACR/EULAR rheumatoid arthritis classification criteria: an analysis based on ESPOIR cohort data. AB - BACKGROUND: In 2010, new classification criteria for rheumatoid arthritis (RA) were developed. OBJECTIVE: To assess agreement between 1987 American College of Rheumatology (ACR) and 2010 ACR/European League Against Rheumatism (EULAR) criteria and the potential source of discordance, based on ESPOIR cohort data. METHODS: 813 early arthritis patients were included in ESPOIR between 2002 and 2005. Between-criteria agreement was based on the kappa coefficient. Discordance was explored by logistic regression. RESULTS: Data for 811 patients were available, with their main characteristics as follows: women 77%, swollen joint count 7.2, tender joint count 8.4, disease activity score in 28 joints 5.2, rheumatoid factor 46%, anticitrullinated protein antibody (ACPA) 39%, structural damage 22%. At baseline, 579 (71.4%) patients met the 1987 ACR criteria and 641 (79.0%) the 2010 criteria. Agreement at baseline was discordant for 168 patients: 115 satisfied the 2010 criteria and 53 the 1987 criteria. Concordance between the two sets was fair, with a kappa coefficient of 0.45 and 0.42 at baseline and year 2, respectively. The main sources of discordance were the number and symmetry of joint involvement, as well as ACPA status. CONCLUSION: 2010 ACR/EULAR criteria identified more patients with RA than did 1987 criteria. The 2010 criteria failed to identify RA patients with symmetrical seronegative arthritis and limited joint involvement. PMID- 22039168 TI - EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis. AB - OBJECTIVES: The authors aim to develop European League Against Rheumatism recommendations for the role of the nurse in the management of patients with chronic inflammatory arthritis, to identify a research agenda and to determine an educational agenda. METHODS: A task force made up of a multidisciplinary expert panel including nurses, rheumatologists, occupational therapist, physiotherapist, psychologist, epidemiologist and patient representatives, representing 14 European countries, carried out the development of the recommendations, following the European League Against Rheumatism standardised operating procedures. The task force met twice. In the first meeting, the aims of the task force were defined, and eight research questions were developed. This was followed by a comprehensive, systematic literature search. In the second meeting, the results from the literature review were presented to the task force that subsequently formulated the recommendations, research agenda and educational agenda. RESULTS: In total, 10 recommendations were formulated. Seven recommendations covered the contribution of nurses to care and management: education, satisfaction with care, access to care, disease management, psychosocial support, self-management and efficiency of care. Three recommendations focused on professional support for nurses: availability of guidelines or protocols, access to education and encouragement to undertake extended roles. The strength of the recommendations varied from A to C, dependent on the category of evidence (1A-3), and a high level of agreement was achieved. Additionally, the task force agreed upon 10 topics for future research and an educational agenda. CONCLUSION: 10 recommendations for the role of the nurse in the management of chronic inflammatory arthritis were developed using a combination of evidence-based and expert consensus approach. PMID- 22039169 TI - Ultrasonographic and MRI characterisation of the palindromic phase of rheumatoid arthritis. PMID- 22039170 TI - Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients. AB - OBJECTIVES: Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA). METHODS: Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (n=3) or other inflammatory arthritis (n=4). IL-34 was detected in the synovial fluid by ELISA and its messenger RNA expression was studied by quantitative PCR in rheumatoid synovial fibroblasts after stimulation by tumour necrosis factor alpha (TNFalpha) and IL-1beta. Wild-type, jnk1(-/-) jnk2(-/-) and nemo(-/-) murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-kappaB) and JNK in that effect. RESULTS: IL-34 was expressed in 24/27 biopsies, with three samples from RA patients being negative. A significant association was found between IL-34 expression and synovitis severity. Levels of IL-34 and the total leucocyte count in synovial fluid were correlated. TNFalpha and IL-1beta stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-kappaB and JNK pathway. CONCLUSION: This work for the first time identifies IL-34 expression in the synovial tissue of patients with arthritis. This cytokine, as a downstream effector of TNFalpha and IL-1beta, may contribute to inflammation and bone erosions in RA. PMID- 22039171 TI - Pharmacokinetics of lisdexamfetamine dimesylate after targeted gastrointestinal release or oral administration in healthy adults. AB - The purpose of this work was to assess the pharmacokinetics and safety of lisdexamfetamine dimesylate (LDX) delivered and released regionally in the gastrointestinal (GI) tract. In this open-label, randomized, crossover study, oral capsules and InteliSite delivery capsules containing LDX (50 mg) with radioactive marker were delivered to the proximal small bowel (PSB), distal SB (DSB), and ascending colon (AC) during separate periods. Gamma scintigraphy evaluated regional delivery and GI transit. LDX and d-amphetamine in blood were measured postdose (<=72 h). Treatment-emergent adverse events (TEAEs) were assessed. Healthy males (n = 18; 18-48 years) were enrolled. Mean (S.D.) maximal plasma concentration (C(max)) was 37.6 (4.54), 40.5 (4.95), 38.7 (6.46), and 25.7 (9.07) ng/ml; area under the concentration-time curve to the last measurable time point was 719.1 (157.05), 771.2 (152.88), 752.4 (163.38), and 574.3 (220.65) ng . h . ml-1, respectively, for d-amphetamine after oral, PSB, DSB, and AC delivery of LDX. Median time to C(max) was 5, 4, 5, and 8 h, respectively. Most TEAEs were mild to moderate. No clinically meaningful changes were observed (laboratory, physical examination, or electrocardiogram). LDX oral administration or targeted delivery to small intestine had similar d-amphetamine systemic exposure, indicating good absorption, and had reduced absorption after colonic delivery. The safety profile was consistent with other LDX studies. PMID- 22039172 TI - Characterization of a human keratinocyte HaCaT cell line model to study the regulation of CYP2S1. AB - CYP2S1 is an extrahepatic cytochrome P450 (P450) that shows marked individuality in constitutive and inducible expression. CYP2S1 mRNA expression is increased in psoriasis and by treatments for psoriasis, including retinoids and UV radiation, although endogenous substrates remain poorly characterized. Because previous model systems have overexpressed modified CYP2S1 in bacteria, human HaCaT keratinocyte cells were screened for constitutive and regulatable CYP2S1 expression and CYP2S1 activity in HaCaT cells compared with a novel Chinese hamster ovary (CHO)-based cell line engineered to stably coexpress CYP2S1 and NADPH cytochrome P450 reductase. Constitutive mRNA expression for CYP2S1 and additional P450s, retinoid acid receptors (RARalpha, RARbeta, RARgamma), and retinoid X receptors (RXRalpha, RXRbeta and RXRgamma) was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis in HaCaT cells. Cells were then exposed to retinoids or to UV radiation (UVR), and changes in CYP2S1 mRNA abundance were further examined by qRT-PCR analysis. P450 expression in HaCaT cells was similar to human skin, with abundant CYP2S1 expression. RARalpha and RARgamma (but not RARbeta) and all RXR isoforms were also detectable. All-trans retinoic acid (atRA) induced CYPS1 mRNA expression more potently than 9-cis RA or 13-cis RA. P450-dependent atRA metabolism was demonstrated in HaCaT cells, with a very similar metabolite profile to that produced by our CYP2S1-expressing CHO cells. CYP2S1 mRNA expression was also induced by UVR, more potently than CYP1B1, a known UVR-inducible P450. Our results demonstrate regulatable and functional CYP2S1 expression in HaCaT cells, thus identifying a human cell line model with utility for further analysis of CYP2S1 regulation and substrate specificity. PMID- 22039173 TI - Assembly, gene annotation and marker development using 454 floral transcriptome sequences in Ziziphus celata (Rhamnaceae), a highly endangered, Florida endemic plant. AB - Large-scale DNA sequence data may enable development of genetic resources in endangered species, thereby facilitating conservation efforts. Ziziphus celata, a federally endangered, self-incompatible plant species occurring in Florida, USA, is one species for which genetic resources are necessary to facilitate new introductions and augmentations essential for recovery of the species. We used 454 pyrosequencing of a Z. celata normalized floral cDNA library to create a genomic resource for gene and marker discovery. A half-plate GS-FLX Titanium run yielded 655 337 reads averaging 250 bp. A total of 474 025 reads were assembled de novo into 84 645 contigs averaging 408 bp, while 181 312 reads remained unassembled. Forty-seven and 43% of contig consensus sequences had BLAST matches to known proteins in the Uniref50 and TAIR9 annotated protein databases, respectively; many contigs fully represented orthologous proteins in TAIR9. A total of 22 707 unique genes were sequenced, indicating substantial coverage of the Z. celata transcriptome. We detected single-nucleotide polymorphisms and simple sequence repeats (SSRs) and developed thousands of SSR primers for use in future genetic studies. As a first step towards understanding self incompatibility in Z. celata, we identified sequences belonging to the gene family encoding self-incompatibility. This study demonstrates the efficacy of 454 transcriptome sequencing for rapid gene and marker discovery in an endangered plant. PMID- 22039175 TI - Management of fever in children. PMID- 22039174 TI - Mutation bias is the driving force of codon usage in the Gallus gallus genome. AB - Synonymous codons are used with different frequencies both among species and among genes within the same genome and are controlled by neutral processes (such as mutation and drift) as well as by selection. Up to now, a systematic examination of the codon usage for the chicken genome has not been performed. Here, we carried out a whole genome analysis of the chicken genome by the use of the relative synonymous codon usage (RSCU) method and identified 11 putative optimal codons, all of them ending with uracil (U), which is significantly departing from the pattern observed in other eukaryotes. Optimal codons in the chicken genome are most likely the ones corresponding to highly expressed transfer RNA (tRNAs) or tRNA gene copy numbers in the cell. Codon bias, measured as the frequency of optimal codons (Fop), is negatively correlated with the G + C content, recombination rate, but positively correlated with gene expression, protein length, gene length and intron length. The positive correlation between codon bias and protein, gene and intron length is quite different from other multi-cellular organism, as this trend has been only found in unicellular organisms. Our data displayed that regional G + C content explains a large proportion of the variance of codon bias in chicken. Stepwise selection model analyses indicate that G + C content of coding sequence is the most important factor for codon bias. It appears that variation in the G + C content of CDSs accounts for over 60% of the variation of codon bias. This study suggests that both mutation bias and selection contribute to codon bias. However, mutation bias is the driving force of the codon usage in the Gallus gallus genome. Our data also provide evidence that the negative correlation between codon bias and recombination rates in G. gallus is determined mostly by recombination-dependent mutational patterns. PMID- 22039176 TI - Paediatric palliative medicine in the UK: past, present, future. AB - Like any new specialty, paediatric palliative medicine is facing challenges as it establishes itself. While many of the required core skills have their roots in adult palliative medicine, its practitioners come from a range of paediatric backgrounds that include oncology, community paediatrics, neurodisability and acute pain. Such heterogeneity has been invaluable in bringing together the diverse set of skills and competencies needed by children and families facing life-limiting illness. At the same time, it brings its own challenges in establishing consistent standards of clinical expertise, education and research- essential if children are to have access to the same degree of medical expertise in palliative care already available to most adults. This article traces the origins of palliative care in children, examines its current strengths and challenges, and considers how those might shape its future. PMID- 22039177 TI - Paediatric societies: increasing student engagement in paediatrics. PMID- 22039178 TI - Nominal deviation in neonatal intensive care units: a time trend analysis. PMID- 22039179 TI - Hospitalisation for bronchiolitis in infants is more common after elective caesarean delivery. AB - BACKGROUND: The authors previously reported an increased risk of hospitalisation for acute lower respiratory infection up to age 2 years in children delivered by elective caesarean section. In view of increasing rates of elective caesarean delivery, this association warranted further investigation. OBJECTIVE: To examine associations between the number of hospital admissions for bronchiolitis and pneumonia and elective caesarean delivery. DESIGN: Retrospective population-based data linkage cohort study of 212 068 non-Aboriginal singleton births of 37-42 weeks gestation. METHODS: Negative binomial regression was used to examine associations between mode of delivery and hospitalisations for both bronchiolitis and pneumonia in children aged <12 months and 12-23 months. Models were adjusted for obstetric and known risk factors. RESULTS: 16% of children were delivered by elective caesarean section (n=33 421). In adjusted analysis, compared with spontaneous vaginal delivery, these children had increased risk of admissions for bronchiolitis at age <12 months (incidence rate ratio (IRR) 1.11; 95% CI 1.01 to 1.23) and 12-23 months (IRR 1.20; 95% CI 0.94 to 1.53) independent of other fetal and maternal factors. There was no association between elective caesarean delivery and number of pneumonia admissions aged <12 months (IRR 1.03; 95% CI 0.80 to 1.33) and 12-23 months (IRR 1.09; 95% CI 0.88 to 1.34). CONCLUSION: Delivery by elective caesarean was independently associated with infant admissions for bronchiolitis but not pneumonia. Elective caesareans or delivery without labour may result in impaired immunity in the newborn leading to increased risk of early viral lower respiratory infections. PMID- 22039180 TI - Recruiting to clinical trials: hospital or home? PMID- 22039181 TI - In people with newly diagnosed type 2 diabetes an intensive dietary intervention, with or without an activity programme, improves glycaemic control over 12 months compared with usual care. PMID- 22039182 TI - Oxytocin for slow progress in the first stage of spontaneous labour is not associated with different rates of caesarean or assisted delivery compared with no treatment or delayed use in second stage. PMID- 22039183 TI - Changing trends in the UK management of childhood ITP. AB - OBJECTIVE: To compare the treatment of childhood immune thrombocytopenia (ITP) with historical practice in the UK. DESIGN: Data collection through a national UK Childhood ITP registry (http://www.uk-itp.org) started in January 2007. SETTINGS: UK hospitals. PARTICIPANTS: Children admitted with a new diagnosis of acute ITP and their treating physicians. MAIN OUTCOME MEASURES: Bleeding severity, platelet count, disease management and outcome from the time of presentation to 6 months. RESULTS: Data from 225 children were analysed. 54% of children had clinically mild, 42% had moderate and 4% had severe disease as defined previously. The mean platelet counts at diagnosis for these groups were 14, 8 and 6*10(9)/l respectively. Children with mild disease had fewer bleeding sites (1.9), compared with moderate (2.5) or severe disease (3.6). There was one intracranial haemorrhage reported. At 6 months' follow-up, 32% had a persistent platelet count <150*10(9)/l, but only 4.8% had a count <20. The proportion of UK children receiving platelet-raising treatment was noted to decrease from 61% in 1995 to 38% in 2000. The current UK 2009 registry data show a continued decrease in treatment to 16% of all the children. In contrast, historical international data report 69% of children receiving interventional therapy. CONCLUSION: The current UK practice has shown a continued reduction in the number of children receiving treatment in comparison with historical data and international practice. PMID- 22039184 TI - Severe refractory dermatitis and cystic fibrosis. PMID- 22039185 TI - Presence of psychiatric disorders is associated with poorer colon cancer outcomes in older adults. PMID- 22039186 TI - In England, a peak in poor mental health in middle-aged people is present only among low-income households. PMID- 22039187 TI - Surveillance and monitoring: a vital investment for the changing burdens of disease. PMID- 22039188 TI - Tranexamic acid--a recipe for saving lives in traumatic bleeding. PMID- 22039189 TI - Apparent prevention of neural tube defects by periconceptional vitamin supplementation. 1981. AB - An earlier preliminary paper is expanded. Women who had given birth to one or more infants with a neural tube defect were recruited into a trial of periconceptional vitamin supplementation. Two hundred mothers attending five centres were fully supplemented (FS), 50 were partially supplemented (PS), and 300 were unsupplemented (US). Neural tube defect recurrences in the study pregnancies were 1(0.5%), in FS, none in PS, and 13 (4%) in US mothers. The difference in outcome between FS and US mothers is significant. The most likely explanation is that supplementation has prevented some neural tube defects, but further studies are needed. PMID- 22039190 TI - Commentary: a brief history of folic acid in the prevention of neural tube defects. PMID- 22039191 TI - Commentary: from controversy and procrastination to primary prevention. PMID- 22039192 TI - Commentary: folate and neural tube defects--the influence of Smithells et al. on research and policy in the Antipodes. PMID- 22039194 TI - Magnitude of effects in clinical trials published in high-impact general medical journals. AB - BACKGROUND: Prestigious journals select for publication studies that are considered most important and informative. We aimed to examine whether high impact general (HIG) medical journals systematically demonstrate more favourable results for experimental interventions compared with the rest of the literature. METHODS: We scrutinized systematic reviews of the Cochrane Database (Issue 4, 2009) and meta-analyses published in four general journals (2008-09). Eligible articles included >=1 binary outcome meta-analysis(es) pertaining to effectiveness with >=1 clinical trial(s) published in NEJM, JAMA or Lancet. Effect sizes in trials from NEJM, JAMA or Lancet were compared with those from other trials in the same meta-analyses by deriving summary relative odds ratios (sRORs). Additional analyses examined separately early- and late-published trials in HIG journals and journal-specific effects. RESULTS: A total of 79 meta analyses including 1043 clinical trials were analysed. Trials in HIG journals had similar effects to trials in other journals, when there was large-scale evidence, but showed more favourable results for experimental interventions when they were small. When HIG trials had less than 40 events, the sROR was 1.64 [95% confidence interval (95% CI): 1.23-2.18). The difference was most prominent when small early trials published in HIG journals were compared with subsequent trials [sROR 2.68 (95% CI: 1.33-5.38)]. Late-published HIG trials showed no consistent inflation of effects. The patterns did not differ beyond chance between NEJM, JAMA or Lancet. CONCLUSIONS: Small trials published in the most prestigious journals show more favourable effects for experimental interventions, and this is most prominent for early-published trials in such journals. No effect inflation is seen for large trials. PMID- 22039193 TI - Is infant weight associated with childhood blood pressure? Analysis of the Promotion of Breastfeeding Intervention Trial (PROBIT) cohort. AB - BACKGROUND: Weight gain during infancy may programme later health outcomes, but examination of this hypothesis requires appropriate lifecourse methods and detailed weight gain measures during childhood. We examined associations between weight gain in infancy and early childhood and blood pressure at the age of 6.5 years in healthy children born at term. METHODS: We carried out an observational analysis of data from a cluster-randomized breastfeeding promotion trial in Belarus. Of 17 046 infants enrolled between June 1996 and December 1997, 13 889 (81.5%) had systolic and diastolic blood pressure measured at 6.5 years; 10 495 children with complete data were analysed. A random-effects linear spline model with three knot points was used to estimate each individual's birthweight and weight gain from birth to 3 months, 3 months to 1 year and 1-5 years. Path analysis was used to separate direct effects from those mediated through subsequent weight gain. RESULTS: In boys, after controlling for confounders and prior weight gain, the change in systolic blood pressure per z-score increase in weight gain was 0.09 mmHg [95% confidence interval (95% CI) -0.14 to 0.31] for birthweight; 0.41 mmHg (95% CI 0.19-0.64) for birth to 3 months; 0.69 mmHg (95% CI 0.47-0.92) for 3 months to 1 year and 0.82 mmHg (95% CI 0.58-1.06) for 1-5 years. Most of the associations between weight gain and blood pressure were mediated through weight at the age of 6.5 years. Findings for girls and diastolic blood pressure were similar. CONCLUSIONS: Children who gained weight faster than their peers, particularly at later ages, had higher blood pressure at the age of 6.5 years, with no association between birthweight and blood pressure. PMID- 22039195 TI - Commentary: decreasing response rates require investigators to quantify and report the impact of selection bias in case-control studies. PMID- 22039196 TI - A synthesis of convenience survey and other data to estimate undiagnosed HIV infection among men who have sex with men in England and Wales. AB - BACKGROUND: Hard-to-reach population subgroups are typically investigated using convenience sampling, which may give biased estimates. Combining information from such surveys, a probability survey and clinic surveillance, can potentially minimize the bias. We developed a methodology to estimate the prevalence of undiagnosed HIV infection among men who have sex with men (MSM) in England and Wales aged 16-44 years in 2003, making fuller use of the available data than earlier work. METHODS: We performed a synthesis of three data sources: genitourinary medicine clinic surveillance (11 380 tests), a venue-based convenience survey including anonymous HIV testing (3702 MSM) and a general population sexual behaviour survey (134 MSM). A logistic regression model to predict undiagnosed infection was fitted to the convenience survey data and then applied to the MSMs in the population survey to estimate the prevalence of undiagnosed infection in the general MSM population. This estimate was corrected for selection biases in the convenience survey using clinic surveillance data. A sensitivity analysis addressed uncertainty in our assumptions. RESULTS: The estimated prevalence of undiagnosed HIV in MSM was 2.4% [95% confidence interval (95% CI 1.7-3.0%)], and between 1.6% (95% CI 1.1-2.0%) and 3.3% (95% CI 2.4-4.1%) depending on assumptions; corresponding to 5500 (3390-7180), 3610 (2180-4740) and 7570 (4790-9840) men, and undiagnosed fractions of 33, 24 and 40%, respectively. CONCLUSIONS: Our estimates are consistent with earlier work that did not make full use of data sources. Reconciling data from multiple sources, including probability-, clinic- and venue-based convenience samples can reduce bias in estimates. This methodology could be applied in other settings to take full advantage of multiple imperfect data sources. PMID- 22039197 TI - Domains of physical activity and all-cause mortality: systematic review and dose response meta-analysis of cohort studies. AB - BACKGROUND: The dose-response relation between physical activity and all-cause mortality is not well defined at present. We conducted a systematic review and meta-analysis to determine the association with all-cause mortality of different domains of physical activity and of defined increases in physical activity and energy expenditure. METHODS: MEDLINE, Embase and the Cochrane Library were searched up to September 2010 for cohort studies examining all-cause mortality across different domains and levels of physical activity in adult general populations. We estimated combined risk ratios (RRs) associated with defined increments and recommended levels, using random-effects meta-analysis and dose response meta-regression models. RESULTS: Data from 80 studies with 1 338 143 participants (118 121 deaths) were included. Combined RRs comparing highest with lowest activity levels were 0.65 [95% confidence interval (95% CI) 0.60-0.71] for total activity, 0.74 (95% CI 0.70-0.77) for leisure activity, 0.64 (95% CI 0.55 0.75) for activities of daily living and 0.83 (95% CI 0.71-0.97) for occupational activity. RRs per 1-h increment per week were 0.91 (95% CI 0.87-0.94) for vigorous exercise and 0.96 (95% CI 0.93-0.98) for moderate-intensity activities of daily living. RRs corresponding to 150 and 300 min/week of moderate to vigorous activity were 0.86 (95% CI 0.80-0.92) and 0.74 (95% CI 0.65-0.85), respectively. Mortality reductions were more pronounced in women. CONCLUSION: Higher levels of total and domain-specific physical activity were associated with reduced all-cause mortality. Risk reduction per unit of time increase was largest for vigorous exercise. Moderate-intensity activities of daily living were to a lesser extent beneficial in reducing mortality. PMID- 22039198 TI - Heavy drinking occasions in relation to ischaemic heart disease mortality-- an 11 22 year follow-up of the 1984 and 1995 US National Alcohol Surveys. AB - BACKGROUND: The relationship between alcohol consumption and ischaemic heart disease (IHD) risk is complex and several issues remain unresolved because many studies used rather crude exposure measures often based on one or two questions. The objective of this study was to investigate the association between heavy drinking occasions and IHD mortality while controlling for average daily alcohol intake and separating former drinkers from lifetime abstainers. METHODS: Cox regression analyses were used with IHD mortality as the outcome in a sample of 9934 participants of the US National Alcohol Surveys conducted in 1984 and 1995. RESULTS: To the end of 2006, 326 deaths from IHD were recorded in the 11- to 22 year follow-up period. Any past heavy drinking occasions in former drinkers [hazard ratio (HR) = 2.06; 95% confidence interval (95% CI): 1.10-3.85] compared with former drinkers without such drinking occasions, and any heavy drinking occasion in current drinkers at baseline (HR = 2.05; 95% CI: 1.03-3.98) compared with current drinkers with average daily intake of one to two drinks, were associated with higher IHD mortality in men and any heavy drinking occasions among drinkers of up to 1 drink average consumption in women with similar effect size. Confounding effects from age, race, education, employment, income, marital status, geographical region, depression score, survey period or other drug use were small. CONCLUSIONS: Among former and current drinkers, heavy drinking occasions should be taken into account when examining the complex association of alcohol consumption on IHD mortality risk. PMID- 22039199 TI - Alcohol imagery and branding, and age classification of films popular in the UK. AB - BACKGROUND: Exposure to alcohol products in feature films is a risk factor for use of alcohol by young people. This study was designed to document the extent to which alcohol imagery and brand appearances occur in popular UK films, and in relation to British Board of Film Classification (BBFC) age ratings intended to protect children and young people from harmful imagery. METHODS: Alcohol appearances (classified as 'alcohol use, inferred alcohol use, other alcohol reference and alcohol brand appearances') were measured using 5-min interval coding of 300 films, comprising the 15 highest grossing films at the UK Box Office each year over a period of 20 years from 1989 to 2008. RESULTS: At least one alcohol appearance occurred in 86% of films, at least one episode of alcohol branding in 35% and nearly a quarter (23%) of all intervals analysed contained at least one appearance of alcohol. The occurrence of 'alcohol use and branded alcohol appearances' was particularly high in 1989, but the frequency of these and all other appearance categories changed little in subsequent years. Most films containing alcohol appearances, including 90% of those including 'alcohol brand appearances', were rated as suitable for viewing by children and young people. The most frequently shown brands were American beers: Budweiser, Miller and Coors. Alcohol appearances were similarly frequent in films originating from the UK, as from the USA. CONCLUSION: Alcohol imagery is extremely common in all films popular in the UK, irrespective of BBFC age classification. Given the relationship between exposure to alcohol imagery in films and use of alcohol by young people, we suggest that alcohol imagery should be afforded greater consideration in determining the suitability of films for viewing by children and young people. PMID- 22039200 TI - In smokers not willing to quit, counselling on smoking reduction plus free nicotine replacement therapy, compared with one-off cessation advice, increases the proportion achieving abstinence or reduction in smoking rate at 6 months. PMID- 22039201 TI - Prenatal exposure to second hand smoke and adverse perinatal outcomes. PMID- 22039202 TI - Review of research findings suggesting nurses overreport their use of research. PMID- 22039203 TI - Changes in patient outcomes coincide with increased nursing hours. PMID- 22039204 TI - Three-year follow-up after introduction of Canadian best practice guidelines for asthma and foot care in diabetes suggests that monitoring of nursing-care indicators using an electronic documentation system promotes sustained implementation. PMID- 22039205 TI - What is quality in qualitative health research? PMID- 22039206 TI - RAPSearch2: a fast and memory-efficient protein similarity search tool for next generation sequencing data. AB - SUMMARY: With the wide application of next-generation sequencing (NGS) techniques, fast tools for protein similarity search that scale well to large query datasets and large databases are highly desirable. In a previous work, we developed RAPSearch, an algorithm that achieved a ~20-90-fold speedup relative to BLAST while still achieving similar levels of sensitivity for short protein fragments derived from NGS data. RAPSearch, however, requires a substantial memory footprint to identify alignment seeds, due to its use of a suffix array data structure. Here we present RAPSearch2, a new memory-efficient implementation of the RAPSearch algorithm that uses a collision-free hash table to index a similarity search database. The utilization of an optimized data structure further speeds up the similarity search-another 2-3 times. We also implemented multi-threading in RAPSearch2, and the multi-thread modes achieve significant acceleration (e.g. 3.5X for 4-thread mode). RAPSearch2 requires up to 2G memory when running in single thread mode, or up to 3.5G memory when running in 4-thread mode. AVAILABILITY AND IMPLEMENTATION: Implemented in C++, the source code is freely available for download at the RAPSearch2 website: http://omics.informatics.indiana.edu/mg/RAPSearch2/. CONTACT: yye@indiana.edu SUPPLEMENTARY INFORMATION: Available at the RAPSearch2 website. PMID- 22039207 TI - STRIKE: evaluation of protein MSAs using a single 3D structure. AB - MOTIVATION: Evaluating alternative multiple protein sequence alignments is an important unsolved problem in Biology. The most accurate way of doing this is to use structural information. Unfortunately, most methods require at least two structures to be embedded in the alignment, a condition rarely met when dealing with standard datasets. RESULT: We developed STRIKE, a method that determines the relative accuracy of two alternative alignments of the same sequences using a single structure. We validated our methodology on three commonly used reference datasets (BAliBASE, Homestrad and Prefab). Given two alignments, STRIKE manages to identify the most accurate one in 70% of the cases on average. This figure increases to 79% when considering very challenging datasets like the RV11 category of BAliBASE. This discrimination capacity is significantly higher than that reported for other metrics such as Contact Accepted mutation or Blosum. We show that this increased performance results both from a refined definition of the contacts and from the use of an improved contact substitution score. CONTACT: cedric.notredame@crg.eu AVAILABILITY: STRIKE is an open source freeware available from www.tcoffee.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22039208 TI - Comments on 'An empirical comparison of several recent epistatic interaction detection methods'. PMID- 22039209 TI - Correcting for cancer genome size and tumour cell content enables better estimation of copy number alterations from next-generation sequence data. AB - MOTIVATION: Comparison of read depths from next-generation sequencing between cancer and normal cells makes the estimation of copy number alteration (CNA) possible, even at very low coverage. However, estimating CNA from patients' tumour samples poses considerable challenges due to infiltration with normal cells and aneuploid cancer genomes. Here we provide a method that corrects contamination with normal cells and adjusts for genomes of different sizes so that the actual copy number of each region can be estimated. RESULTS: The procedure consists of several steps. First, we identify the multi-modality of the distribution of smoothed ratios. Then we use the estimates of the mean (modes) to identify underlying ploidy and the contamination level, and finally we perform the correction. The results indicate that the method works properly to estimate genomic regions with gains and losses in a range of simulated data as well as in two datasets from lung cancer patients. It also proves a powerful tool when analysing publicly available data from two cell lines (HCC1143 and COLO829). AVAILABILITY: An R package, called CNAnorm, is available at http://www.precancer.leeds.ac.uk/cnanorm or from Bioconductor. CONTACT: a.gusnanto@leeds.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22039210 TI - Determining the evolutionary history of gene families. AB - MOTIVATION: Recent large-scale studies of individuals within a population have demonstrated that there is widespread variation in copy number in many gene families. In addition, there is increasing evidence that the variation in gene copy number can give rise to substantial phenotypic effects. In some cases, these variations have been shown to be adaptive. These observations show that a full understanding of the evolution of biological function requires an understanding of gene gain and gene loss. Accurate, robust evolutionary models of gain and loss events are, therefore, required. RESULTS: We have developed weighted parsimony and maximum likelihood methods for inferring gain and loss events. To test these methods, we have used Markov models of gain and loss to simulate data with known properties. We examine three models: a simple birth-death model, a single rate model and a birth-death innovation model with parameters estimated from Drosophila genome data. We find that for all simulations maximum likelihood-based methods are very accurate for reconstructing the number of duplication events on the phylogenetic tree, and that maximum likelihood and weighted parsimony have similar accuracy for reconstructing the ancestral state. Our implementations are robust to different model parameters and provide accurate inferences of ancestral states and the number of gain and loss events. For ancestral reconstruction, we recommend weighted parsimony because it has similar accuracy to maximum likelihood, but is much faster. For inferring the number of individual gene loss or gain events, maximum likelihood is noticeably more accurate, albeit at greater computational cost. AVAILABILITY: www.bioinf.manchester.ac.uk/dupliphy CONTACT: simon.lovell@manchester.ac.uk; simon.whelan@manchester.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22039211 TI - Cascade detection for the extraction of localized sequence features; specificity results for HIV-1 protease and structure-function results for the Schellman loop. AB - MOTIVATION: The extraction of the set of features most relevant to function from classified biological sequence sets is still a challenging problem. A central issue is the determination of expected counts for higher order features so that artifact features may be screened. RESULTS: Cascade detection (CD), a new algorithm for the extraction of localized features from sequence sets, is introduced. CD is a natural extension of the proportional modeling techniques used in contingency table analysis into the domain of feature detection. The algorithm is successfully tested on synthetic data and then applied to feature detection problems from two different domains to demonstrate its broad utility. An analysis of HIV-1 protease specificity reveals patterns of strong first-order features that group hydrophobic residues by side chain geometry and exhibit substantial symmetry about the cleavage site. Higher order results suggest that favorable cooperativity is weak by comparison and broadly distributed, but indicate possible synergies between negative charge and hydrophobicity in the substrate. Structure-function results for the Schellman loop, a helix-capping motif in proteins, contain strong first-order features and also show statistically significant cooperativities that provide new insights into the design of the motif. These include a new 'hydrophobic staple' and multiple amphipathic and electrostatic pair features. CD should prove useful not only for sequence analysis, but also for the detection of multifactor synergies in cross classified data from clinical studies or other sources. AVAILABILITY: Windows XP/7 application and data files available at: https://sites.google.com/site/cascadedetect/home. CONTACT: nacnewell@comcast.net SUPPLEMENTARY INFORMATION: Supplementary information is available at Bioinformatics online. PMID- 22039212 TI - MissForest--non-parametric missing value imputation for mixed-type data. AB - MOTIVATION: Modern data acquisition based on high-throughput technology is often facing the problem of missing data. Algorithms commonly used in the analysis of such large-scale data often depend on a complete set. Missing value imputation offers a solution to this problem. However, the majority of available imputation methods are restricted to one type of variable only: continuous or categorical. For mixed-type data, the different types are usually handled separately. Therefore, these methods ignore possible relations between variable types. We propose a non-parametric method which can cope with different types of variables simultaneously. RESULTS: We compare several state of the art methods for the imputation of missing values. We propose and evaluate an iterative imputation method (missForest) based on a random forest. By averaging over many unpruned classification or regression trees, random forest intrinsically constitutes a multiple imputation scheme. Using the built-in out-of-bag error estimates of random forest, we are able to estimate the imputation error without the need of a test set. Evaluation is performed on multiple datasets coming from a diverse selection of biological fields with artificially introduced missing values ranging from 10% to 30%. We show that missForest can successfully handle missing values, particularly in datasets including different types of variables. In our comparative study, missForest outperforms other methods of imputation especially in data settings where complex interactions and non-linear relations are suspected. The out-of-bag imputation error estimates of missForest prove to be adequate in all settings. Additionally, missForest exhibits attractive computational efficiency and can cope with high-dimensional data. AVAILABILITY: The package missForest is freely available from http://stat.ethz.ch/CRAN/. CONTACT: stekhoven@stat.math.ethz.ch; buhlmann@stat.math.ethz.ch PMID- 22039213 TI - Shoot branching and leaf dissection in tomato are regulated by homologous gene modules. AB - Aerial plant architecture is predominantly determined by shoot branching and leaf morphology, which are governed by apparently unrelated developmental processes, axillary meristem formation, and leaf dissection. Here, we show that in tomato (Solanum lycopersicum), these processes share essential functions in boundary establishment. Potato leaf (C), a key regulator of leaf dissection, was identified to be the closest paralog of the shoot branching regulator Blind (Bl). Comparative genomics revealed that these two R2R3 MYB genes are orthologs of the Arabidopsis thaliana branching regulator REGULATOR OF AXILLARY MERISTEMS1 (RAX1). Expression studies and complementation analyses indicate that these genes have undergone sub- or neofunctionalization due to promoter differentiation. C acts in a pathway independent of other identified leaf dissection regulators. Furthermore, the known leaf complexity regulator Goblet (Gob) is crucial for axillary meristem initiation and acts in parallel to C and Bl. Finally, RNA in situ hybridization revealed that the branching regulator Lateral suppressor (Ls) is also expressed in leaves. All four boundary genes, C, Bl, Gob, and Ls, may act by suppressing growth, as indicated by gain-of-function plants. Thus, leaf architecture and shoot architecture rely on a conserved mechanism of boundary formation preceding the initiation of leaflets and axillary meristems. PMID- 22039214 TI - Strigolactone biosynthesis in Medicago truncatula and rice requires the symbiotic GRAS-type transcription factors NSP1 and NSP2. AB - Legume GRAS (GAI, RGA, SCR)-type transcription factors NODULATION SIGNALING PATHWAY1 (NSP1) and NSP2 are essential for rhizobium Nod factor-induced nodulation. Both proteins are considered to be Nod factor response factors regulating gene expression after symbiotic signaling. However, legume NSP1 and NSP2 can be functionally replaced by nonlegume orthologs, including rice (Oryza sativa) NSP1 and NSP2, indicating that both proteins are functionally conserved in higher plants. Here, we show that NSP1 and NSP2 are indispensable for strigolactone (SL) biosynthesis in the legume Medicago truncatula and in rice. Mutant nsp1 plants do not produce SLs, whereas in M. truncatula, NSP2 is essential for conversion of orobanchol into didehydro-orobanchol, which is the main SL produced by this species. The disturbed SL biosynthesis in nsp1 nsp2 mutant backgrounds correlates with reduced expression of DWARF27, a gene essential for SL biosynthesis. Rice and M. truncatula represent distinct phylogenetic lineages that split approximately 150 million years ago. Therefore, we conclude that regulation of SL biosynthesis by NSP1 and NSP2 is an ancestral function conserved in higher plants. NSP1 and NSP2 are single-copy genes in legumes, which implies that both proteins fulfill dual regulatory functions to control downstream targets after rhizobium-induced signaling as well as SL biosynthesis in nonsymbiotic conditions. PMID- 22039215 TI - TIP: a probabilistic method for identifying transcription factor target genes from ChIP-seq binding profiles. AB - MOTIVATION: ChIP-seq and ChIP-chip experiments have been widely used to identify transcription factor (TF) binding sites and target genes. Conventionally, a fairly 'simple' approach is employed for target gene identification e.g. finding genes with binding sites within 2 kb of a transcription start site (TSS). However, this does not take into account the number of sites upstream of the TSS, their exact positioning or the fact that different TFs appear to act at different characteristic distances from the TSS. RESULTS: Here we propose a probabilistic model called target identification from profiles (TIP) that quantitatively measures the regulatory relationships between TFs and target genes. For each TF, our model builds a characteristic, averaged profile of binding around the TSS and then uses this to weight the sites associated with a given gene, providing a continuous-valued 'regulatory' score relating each TF and potential target. Moreover, the score can readily be turned into a ranked list of target genes and an estimate of significance, which is useful for case-dependent downstream analysis. CONCLUSION: We show the advantages of TIP by comparing it to the 'simple' approach on several representative datasets, using motif occurrence and relationship to knock-out experiments as metrics of validation. Moreover, we show that the probabilistic model is not as sensitive to various experimental parameters (including sequencing depth and peak-calling method) as the simple approach; in fact, the lesser dependence on sequencing depth potentially utilizes the result of a ChIP-seq experiment in a more 'cost-effective' manner. CONTACT: mark.gerstein@yale.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22039216 TI - Sudden cardiac death: mandatory exclusion of athletes at risk is a step too far. AB - Sudden cardiac death (SCD) in young athletes is a distressing event and it is not surprising that some physicians working with sports people are proposing that preventive action should be taken. There is a push for a system similar to that established in some countries, which involves screening and mandatory exclusion of those at risk. We argue that while screening can provide useful information to at-risk athletes making decisions about their future athletic careers, mandatory exclusion of athletes is paternalistic and such decisions are not rightfully within the domain of medicine. PMID- 22039217 TI - Mapping, complementation, and targets of the cysteine protease actinidin in kiwifruit. AB - Cysteine proteases (CPs) accumulate to high concentration in many fruit, where they are believed to play a role in fungal and insect defense. The fruit of Actinidia species (kiwifruit) exhibit a range of CP activities (e.g. the Actinidia chinensis variety YellowA shows less than 2% of the activity of Actinidia deliciosa variety Hayward). A major quantitative trait locus for CP activity was mapped to linkage group 16 in a segregating population of A. chinensis. This quantitative trait locus colocated with the gene encoding actinidin, the major acidic CP in ripe Hayward fruit encoded by the ACT1A-1 allele. Sequence analysis indicated that the ACT1A locus in the segregating A. chinensis population contained one functional allele (A-2) and three nonfunctional alleles (a-3, a-4, and a-5) each containing a unique frameshift mutation. YellowA kiwifruit contained two further alleles: a-6, which was nonfunctional because of a large insertion, and a-7, which produced an inactive enzyme. Site-directed mutagenesis of the act1a-7 protein revealed a residue that restored CP activity. Expression of the functional ACT1A-1 cDNA in transgenic plants complemented the natural YellowA mutations and partially restored CP activity in fruit. Two consequences of the increase in CP activity were enhanced degradation of gelatin-based jellies in vitro and an increase in the processing of a class IV chitinase in planta. These results provide new insight into key residues required for CP activity and the in vivo protein targets of actinidin. PMID- 22039218 TI - Therapeutic interventions for acute hamstring injuries: a systematic review. AB - BACKGROUND: Despite the high rate of hamstring injuries, there is no consensus on their management, with a large number of different interventions being used. Recently several new injection therapies have been introduced. OBJECTIVE: To systematically review the literature on the effectiveness of therapeutic interventions for acute hamstring injuries. DATA SOURCES: The databases of PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL and SPORTDiscus were searched in May 2011. Study eligibility criteria Prospective studies comparing the effect of an intervention with another intervention or a control group without intervention in subjects with acute hamstring injuries were included. DATA ANALYSIS: Two authors independently screened the search results and assessed risk of bias. Quality assessment of the included studies was performed using the Physiotherapy Evidence Database score. A best evidence synthesis was used to identify the level of evidence. MAIN RESULTS: Six studies were included in this systematic review. There is limited evidence for a positive effect of stretching, agility and trunk stability exercises, intramuscular actovegin injections or slump stretching in the management of acute hamstring injuries. Limited evidence was found that there is no effect of non-steroidal anti-inflammatory drugs or manipulation of the sacroiliac joint. CONCLUSIONS: There is a lack of high quality studies on the treatment of acute hamstring injuries. Only limited evidence was found to support the use of stretching, agility and trunk stability exercises, intramuscular actovegin injections or slump stretching. Further research is needed using an appropriate control group, randomisation and blinding. PMID- 22039219 TI - Rhodium dihydride (RhH2) with high volumetric hydrogen density. AB - Materials with very high hydrogen density have attracted considerable interest due to a range of motivations, including the search for chemically precompressed metallic hydrogen and hydrogen storage applications. Using high-pressure synchrotron X-ray diffraction technique and theoretical calculations, we have discovered a new rhodium dihydride (RhH(2)) with high volumetric hydrogen density (163.7 g/L). Compressing rhodium in fluid hydrogen at ambient temperature, the fcc rhodium metal absorbs hydrogen and expands unit-cell volume by two discrete steps to form NaCl-typed fcc rhodium monohydride at 4 GPa and fluorite-typed fcc RhH(2) at 8 GPa. RhH(2) is the first dihydride discovered in the platinum group metals under high pressure. Our low-temperature experiments show that RhH(2) is recoverable after releasing pressure cryogenically to 1 bar and is capable of retaining hydrogen up to 150 K for minutes and 77 K for an indefinite length of time. PMID- 22039220 TI - Conformational dynamics of helix 8 in the GPCR rhodopsin controls arrestin activation in the desensitization process. AB - Arrestins are regulatory molecules for G-protein coupled receptor function. In visual rhodopsin, selective binding of arrestin to the cytoplasmic side of light activated, phosphorylated rhodopsin (P-Rh*) terminates signaling via the G protein transducin. While the "phosphate-sensor" of arrestin for the recognition of receptor-attached phosphates is identified, the molecular mechanism of arrestin binding and the involvement of receptor conformations in this process are still largely hypothetic. Here we used fluorescence pump-probe and time resolved fluorescence depolarization measurements to investigate the kinetics of arrestin conformational changes and the corresponding nanosecond dynamical changes at the receptor surface. We show that at least two sequential conformational changes of arrestin occur upon interaction with P-Rh*, thus providing a kinetic proof for the suggested multistep nature of arrestin binding. At the cytoplasmic surface of P-Rh*, the structural dynamics of the amphipathic helix 8 (H8), connecting transmembrane helix 7 and the phosphorylated C-terminal tail, depends on the arrestin interaction state. We find that a high mobility of H8 is required in the low-affinity (prebinding) but not in the high-affinity binding state. High-affinity arrestin binding is inhibited when a bulky, inflexible group is bound to H8, indicating close interaction. We further show that this close steric interaction of H8 with arrestin is mandatory for the transition from prebinding to high-affinity binding; i.e., for arrestin activation. This finding implies a regulatory role for H8 in activation of visual arrestin, which shows high selectivity to P-Rh* in contrast to the broad receptor specificity displayed by the two nonvisual arrestins. PMID- 22039221 TI - The effect of resident peer-to-peer education on compliance with urinary catheter placement indications in the emergency department. AB - OBJECTIVE This study aims to evaluate the effect of resident peer-to-peer education on knowledge of appropriate urinary catheter (UC) placement in the emergency department (ED) and to determine if this translates into further reduction in UC utilisation. Background Instituting guidelines for appropriate UC placement reduces UC utilisation in the ED. No study has explored if resident education in a teaching hospital would further reduce UC utilisation. METHODS An educational intervention implemented in February 2009 consisted of a lecture, distribution of pocket cards and a peer-administered weekly review of institutional UC guidelines. A 12-question multiple-choice test was given to residents prelecture and postlecture, and the 12-question test was repeated 3 months later. Retrospective chart review was performed to evaluate UC utilisation before, immediately after and 3 months after the educational intervention. RESULTS 30 residents completed all three tests. Significant differences were found between the mean test score pre-education and the mean test score immediately after education (9.43+/-1.17 vs 10.87+/-1.46, p<0.001) and between the mean test score pre-education and the mean test score 3 months posteducation (9.43+/-1.17 vs 10.43+/-1.28, p<0.001). There was no significant difference in UC utilisation or in the proportion of indicated UCs placed by residents within the three study periods. CONCLUSIONS Resident peer-to-peer education was associated with improvement of knowledge but did not result in decreased UC utilisation. A more active approach must be taken and other factors need to be further explored to reduce unnecessary placement of UC by residents in the ED. PMID- 22039222 TI - Regarding prostate-specific antigen: let's not shoot the messenger. PMID- 22039223 TI - Tension at the borders: perceptions of role overload, conflict, strain and facilitation in work, family and health roles among employed individuals with arthritis. AB - OBJECTIVE: To examine inter-relationships among arthritis (A), work (W) and personal life (P) roles and their reciprocal influences, especially experiences of role balance/imbalance among individuals with inflammatory arthritis (IA) and OA. METHODS: Eight focus groups were conducted with 24 women and 16 men (aged 29 72 years). A purposive sample was recruited from community advertising. Eligibility included current employment or having been employed within the previous year. Participants were asked about ways arthritis, work and personal life roles intersected and their impact. A standardized questionnaire collected demographic, symptom and employment data for descriptive purposes. RESULTS: Participants noted that having arthritis affected their identity and intersected with work and personal roles, creating role overload, role conflict, role strain and role facilitation. Role overload highlighted that arthritis both affected and was impacted by work and personal life (A -> W; A -> P; W -> A; P -> A). Role conflict focused on A -> W and A -> P difficulties, whereas role facilitation emphasized the positive impact of work and personal life roles on arthritis (W -> A; P -> A). Role strain was pervasive and arose from numerous sources. Personal strategies (e.g. positive framing) and contextual factors (e.g. support) were important in contributing to or ameliorating role balance/imbalance. CONCLUSIONS: By comprehensively examining multiple types of role balance/imbalance and the context within which it occurs, this study identifies gaps in patient-oriented measurement of the impact of arthritis and areas of need in the development of arthritis intervention. PMID- 22039224 TI - Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signalling and strengthens the role of IRF5 in disease susceptibility in a Northern European population. AB - OBJECTIVE: A large number of genes, including several not previously implicated in SLE susceptibility, have recently been identified or confirmed by genome-wide association studies (GWAS). In this study, we sought to replicate some of these results in Finnish SLE patients (n = 275) and control individuals (n = 356). METHODS: We genotyped 32 single nucleotide polymorphisms (SNPs) in 12 of the best supported GWAS-identified SLE genes and loci. We further investigated gene-gene interactions between the loci included in the study. RESULTS: The strongest evidence of association was found at the IRF5-TNPO3 locus, with the most significant P-value being 2.0 * 10(-7) and an odds ratio of 1.95 (95% CI 1.51, 2.50). Association between SLE and TNFAIP3, FAM167A-BLK, BANK1 and KIAA1542 was also confirmed, although at a lower significance level and contribution to individual risk. No significant association was found with 1q25.1, PXK, ATG5, ICA1, XKR6, LYN and SCUBE1. Furthermore, no significant gene-gene interactions were detected. CONCLUSION: Replication of previous GWAS findings across diverse populations is of importance to validate these associations and to get a better understanding of potential genetic heterogeneity between populations in SLE susceptibility. Our results attest the importance of B-cell receptor pathway and IFN signalling in SLE pathogenesis. PMID- 22039225 TI - Thoracic spine osteitis: a distinct clinical entity, a variant of SAPHO or late onset non-bacterial osteitis? PMID- 22039226 TI - Biologic agents for rheumatoid arthritis--negotiating the NICE technology appraisals. AB - In England and Wales, the National Institute for Health and Clinical Excellence (NICE) has provided guidance [technology appraisals (TAs) 130, 186, 195, 198 and 225] on the use of biologic drugs for the treatment of RA. This is based on an analysis of efficacy, safety and cost-effectiveness, and has resulted in a complex management pathway that restricts freedom to prescribe biologics according to their licensed indications. Specifically, TNF antagonists are the only class of biologics that can be used first line in DMARD-inadequate responders, and only in patients with a persistent 28-joint DAS score of >=5.1. Alternative biologic agents are denied to those with contraindications to anti TNF drugs and are also not supported following intolerance to TNF antagonists. Rituximab is the only class of biologic permitted after TNF antagonist inefficacy, in the absence of a contraindication to its use, whereas abatacept and tocilizumab are licensed and may be a more efficacious choice at this stage in some patient groups. Furthermore, for patients who demonstrate sequential inadequate responses, treatment is restricted to one TNF antagonist, rituximab and tocilizumab, whereas abatacept is only a permitted choice when rituximab is contraindicated or has been withdrawn because of an adverse event. In this review, we discuss the treatment algorithm published by NICE, and suggest alternatives where perceived deficiencies exist. PMID- 22039227 TI - Do low vitamin D levels cause problems of waste removal in patients with SLE? PMID- 22039228 TI - Inflammatory cytokine expression in the skin lesions of tumour necrosis factor receptor-associated periodic syndrome. PMID- 22039229 TI - A novel mechanism of increased infections in contact lens wearers. AB - PURPOSE: It is well documented that contact lens wearers have much higher incidences of corneal infections compared with those of non-contact lens wearers, although the exact cause(s) of this increased susceptibility has not been identified. A distinct subset of mucins (MUCs) is present on the ocular surface, acting to protect the integrity of the corneal epithelium. This study was performed to determine whether multipurpose contact lens solutions (MPCLSs) can cause increased infections in the cornea by destroying the protective cell-bound mucin layer. METHODS: An immortalized human corneal limbal epithelial cell line was treated in the presence of four commonly used MPCLSs or PBS and the expression and release of MUC-16 was assessed. Cells were also cultured with Pseudomonas aeruginosa after MPCLS treatment and internalization of bacteria was assessed by quantitative genomic PCR. Loss of MUC-16 was then correlated with infection rates. RESULTS: Each of the four commonly used MPCLSs examined in this study differentially affected mucin release. The relative effect was correlated with an increase in infection of corneal epithelial cells by P. aeruginosa. CONCLUSIONS: The results of this study are consistent with the hypothesis that MPCLSs cause increased infections in the cornea by destroying the protective cell bound mucin layer. PMID- 22039230 TI - Decrease in rate of myopia progression with a contact lens designed to reduce relative peripheral hyperopia: one-year results. AB - PURPOSE: To determine whether a novel optical treatment using contact lenses to reduce relative peripheral hyperopia can slow the rate of progress of myopia. METHODS: Chinese children, aged 7 to 14 years, with baseline myopia from sphere 0.75 to -3.50 D and cylinder <=1.00 D, were fitted with novel contact lenses (n = 45) and followed up for 12 months, and their progress was compared with that of a group (n = 40) matched for age, sex, refractive error, axial length, and parental myopia wearing normal, single-vision, spherocylindrical spectacles. RESULTS: On adjusting for parental myopia, sex, age, baseline spherical equivalent (SphE) values, and compliance, the estimated progression in SphE at 12 months was 34% less, at -0.57 D, with the novel contact lenses (95% confidence interval [CI], 0.45 -0.69 D) than at -0.86 D, with spectacle lenses (95% CI, -0.74 to -0.99 D). For an average baseline age of 11.2 years, baseline SphE of -2.10 D, a baseline axial length of 24.6 mm, and 320 days of compliant lens wear, the estimated increase in axial length (AL) was 33% less at 0.27 mm (95% CI, 0.22-0.32 mm) than at 0.40 mm (95% CI, 0.35-0.45 mm) for the contact lens and spectacle lens groups, respectively. CONCLUSIONS: The 12-month data support the hypothesis that reducing peripheral hyperopia can alter central refractive development and reduce the rate of progress of myopia. (chictr.org number, chiCTR-TRC-00000029 or chiCTR-TRC 00000032.). PMID- 22039231 TI - Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine for Streptococcus pneumoniae Keratitis. AB - PURPOSE: The purpose of this study was to determine whether active immunization against pneumolysin (PLY), or polysaccharide capsule, protects against the corneal damage associated with Streptococcus pneumoniae keratitis. METHODS: New Zealand White rabbits were actively immunized with Freund's adjuvant mixed with pneumolysin toxoid (psiPLY), Pneumovax 23 (PPSV23; Merck, Whitehouse Station, NJ), or phosphate-buffered saline (PBS), before corneal infection with 105 colony forming units (CFU) of S. pneumoniae. Serotype-specific rabbit polyclonal antisera or mock antisera were passively administered to rabbits before either intravenous infection with 1011 CFU S. pneumoniae or corneal infection with 105 CFU of S. pneumoniae. RESULTS: After active immunization, clinical scores of corneas of the rabbits immunized with psiPLY and Freund's adjuvant were significantly lower than scores of the rabbits that were mock immunized with PBS and Freund's adjuvant or with PPSV23 and Freund's adjuvant at 48 hours after infection (P <= 0.0010), whereas rabbits immunized with PPSV23 and Freund's adjuvant failed to show differences in clinical scores compared with those in mock-immunized rabbits (P = 1.00) at 24 and 48 hours after infection. Antisera from rabbits actively immunized with PPSV23 and Freund's adjuvant were nonopsonizing. Bacterial loads recovered from infected corneas were higher for the psiPLY- and PPSV23-immunized rabbits after infection with WU2, when compared with the mock-immunized rabbits (P <= 0.007). Conversely, after infection with K1443, the psiPLY-immunized rabbits had lower bacterial loads than the control rabbits (P = 0.0008). Quantitation of IgG, IgA, and IgM in the sera of psiPLY immunized rabbits showed high concentrations of PLY-specific IgG. Furthermore, anti-PLY IgG purified from psiPLY-immunized rabbits neutralized the cytolytic effects of PLY on human corneal epithelial cells. Passive administration of serotype-specific antisera capable of opsonizing and killing S. pneumoniae protected against pneumococcal bacteremia (P <= 0.05), but not against keratitis (P >= 0.476). CONCLUSIONS: Active immunization with pneumococcal capsular polysaccharide and Freund's adjuvant fails to produce opsonizing antibodies, and passive administration of serotype specific opsonizing antibodies offers no protection against pneumococcal keratitis in the rabbit, whereas active immunization with the conserved protein virulence factor PLY and Freund's adjuvant is able to reduce corneal inflammation associated with pneumococcal keratitis, but has variable effects on bacterial loads in the cornea. PMID- 22039232 TI - Vulnerability of the retinal microvasculature to hypoxia: role of polyamine regulated K(ATP) channels. AB - PURPOSE: It is uncertain why retinal capillaries are particularly vulnerable to hypoxia. In this study, it was hypothesized that their specialized physiology, which includes being the predominant microvascular location of functional adenosine triphosphate-sensitive potassium (K(ATP)) channels, boosts their susceptibility to hypoxia-induced cell death. METHODS: Cell viability, ionic currents, intracellular calcium, and pericyte contractility in microvascular complexes freshly isolated from the rat retina were assessed using trypan blue dye exclusion, perforated-patch recordings, fura-2 fluorescence, and time-lapse videos. Chemical hypoxia was induced by antimycin, an oxidative phosphorylation inhibitor. RESULTS: In freshly isolated retinal microvascular complexes, chemical hypoxia caused more cell death in capillaries than in arterioles. Indicative of the role of polyamine-dependent K(ATP) channels, antimycin-induced capillary cell death was markedly decreased in microvessels treated with the polyamine synthesis inhibitor, difluoromethylornithine, or the K(ATP) channel inhibitor, glibenclamide. These inhibitors also diminished the antimycin-induced hyperpolarization, as well as the antimycin-induced intracellular calcium increase, which was significantly dependent on extracellular calcium and was diminished by the inhibitor of calcium-induced calcium release (CICR), dantrolene. Consistent with the importance of the CICR-dependent increase in capillary cell calcium, dantrolene significantly decreased hypoxia-induced capillary cell death. We also found that activation of the polyamine/K(ATP) channel/Ca(2+) influx/CICR pathway not only boosted the vulnerability of retinal capillaries to hypoxia, but also caused the contraction of capillary pericytes, whose vasoconstrictive effect may exacerbate hypoxia. CONCLUSIONS: The vulnerability of retinal capillaries to hypoxia is boosted by a mechanism involving the polyamine/K(ATP) channel/Ca(2+) influx/CICR pathway. Discovery of this pathway should provide new targets for pharmacological interventions to minimize hypoxia-induced damage in retinal capillaries. PMID- 22039233 TI - Alterations in protein expression in tree shrew sclera during development of lens induced myopia and recovery. AB - PURPOSE: During the development of, and recovery from, negative lens-induced myopia there is regulated remodeling of the scleral extracellular matrix (ECM) that controls the extensibility of the sclera. Difference gel electrophoresis (DIGE) was used to identify and categorize proteins whose levels are altered in this process. METHODS: Two groups of five tree shrews started monocular lens wear 24 days after eye opening (days of visual experience [VE]). The lens-induced myopia (LIM) group wore a -5 D lens for 4 days. The recovery (REC) group wore a 5 D lens for 11 days and then recovered for 4 days. Two normal groups (28 and 39 days of VE; n = 5 each) were also examined, age-matched to each of the treatment groups. Refractive and A-scan measures confirmed the effect of the treatments. Scleral proteins were isolated and resolved by DIGE. Proteins that differed in abundance were identified by mass spectrometry. Ingenuity pathway analysis was used to investigate potential biological pathway interactions. RESULTS: During normal development (28-39 days of VE), eight proteins decreased and one protein increased in relative abundance. LIM-treated eyes were myopic and longer than control eyes; LIM-control eyes were slightly myopic compared with 28N eyes, indicating a yoking effect. In both the LIM-treated and the LIM-control eyes, there was a general downregulation from normal of proteins involved in transcription, cell adhesion, and protein synthesis. Additional proteins involved in cell adhesion, actin cytoskeleton, transcriptional regulation, and ECM structural proteins differed in the LIM-treated eyes versus normal but did not differ in the control eyes versus normal. REC-treated eyes were recovering from the induced myopia. REC-control eye refractions were not significantly different from the 39N eyes, and few proteins differed from age-matched normal eyes. The balance of protein expression in the REC-treated eyes, compared with normal eyes and REC-control eyes, shifted toward upregulation or a return to normal levels of proteins involved in cell adhesion, cell division, cytoskeleton, and ECM structural proteins, including upregulation of several cytoskeleton-related proteins not affected during myopia development. CONCLUSIONS: The DIGE procedure revealed new proteins whose abundance is altered during myopia development and recovery. Many of these are involved in cell-matrix adhesions, cytoskeleton, and transcriptional regulation and extend our understanding of the remodeling that controls the extensibility of the sclera. Reductions in these proteins during minus lens wear may produce the increased scleral viscoelasticity that results in faster axial elongation. Recovery is not a mirror image of lens-induced myopia many protein levels, decreased during LIM, returned to normal, or slightly above normal, and additional cytoskeleton proteins were upregulated. However, no single protein or pathway appeared to be responsible for the scleral changes during myopia development or recovery. PMID- 22039234 TI - Autosomal dominant retinitis pigmentosa with intrafamilial variability and incomplete penetrance in two families carrying mutations in PRPF8. AB - PURPOSE: The aim of this study was to report detailed genotype/phenotype correlation in two British autosomal dominant retinitis pigmentosa (adRP) families with recently described mutations in PRPF8. METHODS: Ten affected members from the two families (excluded for PRPF31 mutations) were assessed clinically. Seven subjects had fundus photography; some had electrophysiology, autofluorescence imaging, and visual field testing. Linkage analysis was performed from genomic DNA in one family. RNA was extracted from lymphocytes of the proband from both families, reverse transcribed into cDNA and subsequently screened for mutations in PRPF8. Segregation of mutations in each family was tested by direct genomic sequencing of the specific exons carrying the mutation. RESULTS: All affected members complained of nyctalopia with variable age of onset. In the first family, there was marked variation in the clinical phenotype among affected individuals ranging from severe rod-cone dystrophy to a 67-year old patient with a normal retinal appearance and mild rod dysfunction on scotopic electroretinography (ERG). The second family demonstrated similar variability and a history of a nonpenetrant individual. Linkage analysis in the first family showed strong evidence for linkage to markers on chromosome 17p implicating PRPF8 as a candidate gene. A c.6353 C>T change causing a nonconservative missense mutation p.S2118F was found in exon 38 of PRPF8 by direct sequencing of the cDNA. The mutation c.6930G>C (p.R2310S) was found in the second family. CONCLUSIONS: This is the first report of marked intrafamilial variability associated with mutations in the PRPF8 gene, including incomplete penetrance. PRPF8 mutations should be suspected in patients with adRP and variable expressivity. PMID- 22039235 TI - Insight into the role of Ca2+-binding protein 5 in vesicle exocytosis. AB - PURPOSE: CaBP5 is a neuronal calmodulin-like Ca(2+)-binding protein that is expressed in the retina and in the cochlea. Although CaBP5 knockout mice displayed reduced sensitivity of retinal ganglion cell light responses, the function of CaBP5 in vivo is still unknown. To gain further insight into CaBP5 function, the authors screened for CaBP5-interacting partners. METHODS: Potential retinal interacting partners for CaBP5 were identified using affinity chromatography followed by mass spectrometry and by yeast two-hybrid screening of a bovine retina cDNA library. Interacting partners were further analyzed using coimmunoprecipitation. Immunohistochemistry and subcellular fractionation were performed to determine their colocalization in the retina. The effect of CaBP5 on dopamine release and neurite outgrowth of PC12 cells was analyzed using ELISA and fluorescent labeling. RESULTS: Using affinity chromatography, the authors identified Munc18-1 and myosin VI as interacting partners for CaBP5. Munc18-1 was also identified using the yeast two-hybrid system. Colocalization and coimmunoprecipitation of CaBP5 with these two proteins in retinal tissue further established their physiological interactions. Furthermore, CaBP5 expression in NGF-stimulated PC12 cells stimulates neurite outgrowth and dopamine exocytosis. CONCLUSIONS: This study shows that CaBP5 interacts with Munc18-1 and myosin VI, two proteins involved in the synaptic vesicle cycle. Together with the effect of CaBP5 in stimulating neurite outgrowth and vesicle exocytosis in PC12 cells, these results suggest that CaBP5 plays a role in neurotransmitter release. PMID- 22039236 TI - Determinants of quantitative optic nerve measurements using spectral domain optical coherence tomography in a population-based sample of non-glaucomatous subjects. AB - PURPOSE: To evaluate the ocular and systemic factors influencing measurements of optic nerve head (ONH) parameters and retinal nerve fiber layer (RNFL) thickness with spectral-domain optical coherence tomography (SD-OCT) in healthy Chinese adults. METHODS: Adults ranging in age from 40 to 80 years were consecutively recruited from the population-based Singapore Chinese Eye Study. A SD-OCT instrument was used to measure ONH and RNFL parameters. A total of 542 eyes from 542 non-glaucomatous Chinese subjects were analyzed. Univariable and multiple linear regression analyses were performed to examine the effects of a range of ocular (e.g., intraocular pressure [IOP], axial length [AL], disc area) and systemic (e.g., blood pressure, serum glucose) factors on ONH and RNFL parameters. RESULTS: In multiple regression analyses, neuroretinal rim area was independently associated with age (beta = -0.006, P < 0.001), disc area (beta = 0.183, P < 0.001), IOP (beta = -0.009, P = 0.008), AL (beta = -0.023, P = 0.004), and lens nuclear color (beta = 0.042, P = 0.001). Vertical cup-to-disc ratio was independently correlated with age (beta = 0.003, P < 0.001), disc area (beta = 0.207, P < 0.001), IOP (beta = 0.004, P = 0.014), AL (beta = 0.010, P = 0.008), and lens nuclear color (beta = -0.017, P = 0.006). Average RNFL thickness was independently related to age (beta = -0.204, P = 0.001), disc area (beta = 4.218, P < 0.001), signal strength (beta = 1.348, P < 0.001), and AL (beta = -1.332, P < 0.001). Disc area had the strongest effect on measurements of ONH parameters and RNFL thickness. CONCLUSIONS: In a non-glaucomatous population, optic nerve measurements with SD-OCT vary with disc area, age, IOP, AL, lens nuclear color, and signal strength, but systemic parameters have little influence. This information may be useful for interpretation of SD-OCT measurements. PMID- 22039237 TI - Increase of intracellular Ca2+ by purinergic receptors in cultured rat lacrimal gland myoepithelial cells. AB - PURPOSE: To isolate and characterize cultured myoepithelial cells (MECs) from rat lacrimal gland and determine which purinergic receptor subtypes are present and functional in MECs. METHODS: Rat lacrimal glands were subjected to collagenase digestion, and MECs were grown. RT-PCR was performed for the purinergic receptors P2X(7), P2Y(1), P2Y(11), and P2Y(13) on RNA isolated from the MECs. Immunofluorescence experiments were performed with antibodies against MEC markers and P2X(7), P2Y(1), P2Y(11), and P2Y(13) purinergic receptors. Proteins from MECs were separated using Western blot analysis techniques. In addition, cells were incubated with Fura 2 tetra acetoxymethyl ester, and intracellular [Ca(2+)] ([Ca(2+)](i)) was determined in response to P2 purinergic agonists. RESULTS: MECs expressed the MEC proteins alpha-smooth muscle actin, vimentin, alpha-actinin, and adenylyl cyclase II. RT-PCR, Western blot, and immunofluorescence techniques demonstrated the presence of the purinergic receptors P2X(7), P2Y(1), P2Y(11), and P2Y(13). The purinergic agonists ATP, benzoylbenzoyl ATP (BzATP), alpha,beta methylene ATP, UTP, 2-methylthioATP (MeSATP), and ATPgammaS increased [Ca(2+)](i). As BzATP binds to the P2X(7) receptor, specific characteristics of this receptor were investigated. Neither inhibitors of P2X(7) receptors nor removal of extracellular Mg(2+) or Ca(2+) had an effect on the BzATP-stimulated increase in [Ca(2+)](i). Repeated applications of BzATP desensitized this response. Inhibitors for P2Y(1), P2Y(11), and P2Y(13) each decreased the BzATP stimulated increase in [Ca(2+)](i) with the P2Y(1) inhibitor most effective. CONCLUSIONS: MECs can be isolated from rat lacrimal glands, and they express P2X(7), P2Y(1), P2Y(11), and P2Y(13) purinergic receptors. Surprisingly, BzATP binds the P2Y(1) receptor, which is primarily responsible for the BzATP stimulated increase in [Ca(2+)](i). PMID- 22039238 TI - Central retinal function as measured by the multifocal electroretinogram and flicker perimetry in early age-related macular degeneration. AB - PURPOSE: To determine the retinal function in early age-related macular degeneration (AMD) assessed by the multifocal electroretinogram (mfERG) and flicker perimetry and to seek a relationship between local objective mfERG parameters and subjective flicker perimetry thresholds. METHODS: mfERG and flicker perimetry were performed in 15 patients (15 eyes) with early AMD and 14 controls (14 eyes) of similar age. The mfERG P1 response amplitude density (nV/deg2) and P1 implicit time of the first-order kernel and the flicker thresholds of each concentric ring were analyzed. The relationship between individual mfERG responses and the corresponding individual flicker sensitivity outcomes was determined. RESULTS: The mfERG response amplitude of the central ring (ring 1) was significantly reduced in early AMD eyes compared with the controls (P = 0.009). No significant difference in mfERG amplitude between early AMD and control eyes was detected in the other rings. The mfERG implicit time was significantly increased in the early AMD eyes but only within the central four rings of 12 degrees . A significant reduction in flicker sensitivity was also detected in early AMD eyes but only within the central 6 degrees . There was a significant, moderate correlation (r = -0.477; P < 0.001) between local mfERG latency and flicker sensitivity from the same tested locations within the central 6 degrees . There was a weak correlation (r = 0.200; P = 0.014) between mfERG amplitude and flicker sensitivity. CONCLUSIONS: Both mfERG and flicker perimetry show abnormal retinal function, but only in the very central macula, in early AMD. A novel relationship between mfERG and flicker sensitivity should enhance the clinical monitoring of disease progression. PMID- 22039239 TI - Carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) in posterior uveal melanoma: correlation with clinical and histological survival markers. AB - PURPOSE: Carcinoembryonic antigen cell adhesion molecule (CEACAM)-1 is a multi functional protein, with strong predictive value for poor prognosis when found in primary cutaneous melanoma lesions. In this study, the expression of CEACAM1 in uveal melanoma was correlated with clinicopathologic parameters. METHODS: CEACAM1 expression was immunohistochemically evaluated in 79 primary uveal melanomas and 21 liver metastases of patients who were treated at the Hadassah-Hebrew University Medical Center between the years 1986 and 2006. The findings were correlated with location, cell type, extracellular matrix patterns, tumor size, and metastatic disease. RESULTS: CEACAM1 was expressed in 45% of the primary tumors compared with 81% of the metastases (Fisher's exact test, P = 0.003). There was no significant association between CEACAM1 and location of the primary tumors. Histologically, CEACAM1 was associated with epithelioid-type tumors (69.6%), but not with spindle-type tumors (25.0%) (Cramer's V = 0.354; P = 0.019). Also it was significantly associated with network extracellular matrix pattern (73.3%), but not with silent pattern (11.8%) (Cramer's V = 0.510; P = 0.004). CEACAM1-positive tumors were not statistically different in size from CEACAM1-negative tumors. The higher frequency of CEACAM1 in patients who ultimately developed metastases (58.8% vs. 41.7%) was not statistically significant (likelihood ratio chi(2) = 2.069; P = 0.1503). CONCLUSIONS: This report describes CEACAM1 expression in uveal melanoma. Correlation with poor prognostic factors such as epithelioid cell type and networks of extracellular matrix pattern was found, but definitive prognostic conclusions still cannot be deduced. Additional validation studies on the use of CEACAM1 expression as a prognostic marker are warranted. PMID- 22039240 TI - eNOS, a pressure-dependent regulator of intraocular pressure. AB - PURPOSE: Pathology in the primary drainage pathway for aqueous humor in the eye is responsible for ocular hypertension, the only treatable risk factor in patients with glaucoma. Unfortunately, the mechanisms that regulate pressure dependent drainage of aqueous humor and thus intraocular pressure (IOP) are unknown. To better understand one possible underlying molecular factor that regulates IOP, nitric oxide (NO), pressure-dependent drainage in transgenic mice overexpressing endothelial NO synthase (eNOS) was studied. METHODS: IOP was measured by rebound tonometry in mice, and pressure versus flow data were measured by ex vivo perfusion at multiple pressures between 8 and 45 mm Hg, using mock AH +/-100 MUM L-NAME. A subset of eyes was examined histologically using standard techniques or was assayed for fusion protein expression by Western blot analysis. RESULTS: IOP was lower (9.6 +/- 2.7 vs. 11.4 +/- 2.5 mm Hg; mean +/- SD; P = 0.04) and pressure-dependent drainage was higher (0.0154 +/- 0.006 vs. 0.0066 +/- 0.0009 MUL/min/mm Hg; P = 0.002) in the transgenic mice than in the wild-type animals; however, pressure-independent drainage was unaffected. The NOS inhibitor L-NAME normalized pressure-dependent drainage in transgenic animals. For IOP >35 mm Hg, the slope of the pressure-flow curve in wild-type mice increased to match that seen in transgenic mice. Shear stress in the pressure dependent pathway at elevated pressures was calculated to be in a range known to affect eNOS expression and activity in vascular endothelia. CONCLUSIONS: Endothelial NOS overexpression lowers IOP by increasing pressure-dependent drainage in the mouse eye. Data are consistent with NO's having a mechanoregulatory role in aqueous humor dynamics, with eNOS induction at elevated IOPs leading to increased pressure-dependent outflow. PMID- 22039241 TI - X-linked retinoschisis: RS1 mutation severity and age affect the ERG phenotype in a cohort of 68 affected male subjects. AB - PURPOSE: To assess the effect of age and RS1 mutation on the phenotype of X linked retinoschisis (XLRS) subjects using the clinical electroretinogram (ERG) in a cross-sectional analysis. METHODS: Sixty-eight XLRS males 4.5 to 55 years of age underwent genotyping, and the retinoschisis (RS1) mutations were classified as less severe (27 subjects) or more severe (41 subjects) based on the putative impact on the protein. ERG parameters of retinal function were analyzed by putative mutation severity with age as a continuous variable. RESULTS: The a-wave amplitude remained greater than the lower limit of normal (mean, -2 SD) for 72% of XLRS males and correlated with neither age nor mutation class. However, b-wave and b/a-ratio amplitudes were significantly lower in the more severe than in the less severe mutation groups and in older than in younger subjects. Subjects up to 10 years of age with more severe RS1 mutations had significantly greater b-wave amplitudes and faster a-wave trough implicit times than older subjects in this group. CONCLUSIONS: RS1 mutation putative severity and age both had significant effects on retinal function in XLRS only in the severe mutation group, as judged by ERG analysis of the b-wave amplitude and the b/a-ratio, whereas the a-wave amplitude remained normal in most. A new observation was that increasing age (limited to those aged 55 and younger) caused a significant delay in XLRS b-wave onset (i.e., a-wave implicit time), even for those who retained considerable b wave amplitudes. The delayed b-wave onset suggested that dysfunction of the photoreceptor synapse or of bipolar cells increases with age of XLRS subjects. PMID- 22039242 TI - Microglia-mediated IGF-I neuroprotection in the rd10 mouse model of retinitis pigmentosa. AB - PURPOSE: To characterize the effect of IGF-I in the rd10 mouse model of retinitis pigmentosa at the cellular level, focusing on the role of microglia in the neurodegenerative process. METHODS: Both organotypic retinal explants and intravitreal injections were used to assess the effect of IGF-I on photoreceptor cell death in the Pde6b(rd10) mice. Cell death was determined by TUNEL in retinal sections and by ELISA of free nucleosomes in retinal extracts. The number and distribution of microglial cells was visualized by immunolabeling with Cd11b and Iba1 antibodies. Depletion of microglia in culture was achieved by treatment with liposomes containing clodronate. RESULTS: Both ex vivo and in vivo IGF-I treatment reduced the number of TUNEL-positive nuclei in rd10 mouse retinas. In addition, IGF-I treatment in explants increased the number of microglial cells in the ONL. Depletion of microglia in explants with liposomes containing clodronate diminished the neuroprotective effect of IGF-I but also moderately reduced photoreceptor cell death in rd10 retinas cultured in the absence of IGF-I. CONCLUSIONS: IGF-I is able to attenuate photoreceptor cell death both ex vivo and in vivo in the rd10 mouse retina. Microglia is required for the neuroprotective effect of IGF-I in the dystrophic retina. In addition, microglial cells play a detrimental role, seemingly led to neuroprotection by IGF-I. PMID- 22039243 TI - Intraocular pressure measurement by radio wave telemetry. AB - PURPOSE: To determine the biocompatibility of a new wireless intraocular pressure (IOP) transducer (WIT) in rabbit eyes and to correlate its measurements with other pressure-measuring devices. METHODS: The WIT is a ring-shaped intraocular device that allows wireless IOP measurements through radiofrequency. It was implanted into six eyes of New Zealand White rabbits after extracapsular lens extraction. A sham rabbit eye with no transducer implanted was used as a control. The animals were observed and examined by microscopy at various intervals up to 25 months after surgery. IOP was measured at various intervals by pneumotonometry, tonometry, WIT, and manometry. The data from the various devices were compared and analyzed for reproducibility. Two eyes were enucleated at 5.5 and 20 months after implantation and analyzed by histology. RESULTS: The WIT appears to be well tolerated in the rabbit eye, with no evidence of significant inflammation or scar formation by microscopic in vivo examination. Histology did not reveal intraocular inflammation or membrane formation. Repeated IOP measurements with pneumotonometry, tonometry, and the WIT resulted in SDs of 2.70 mm Hg, 3.35 mm Hg, and 0.81 mm Hg, respectively. The concordance between the WIT and direct manometry measurements was high. A downward drift in IOP measured by the WIT was noted in three rabbits, necessitating recalibration. CONCLUSIONS: The WIT is well tolerated by the rabbit eye. Its measurements are reproducible and in close concordance with manometry. A downward IOP drift warrants further investigation. PMID- 22039244 TI - A method to enhance cell survival on Bruch's membrane in eyes affected by age and age-related macular degeneration. AB - PURPOSE: To determine whether conditioned medium (CM) derived from bovine corneal endothelial cells (BCECs) can support transplanted cells on aged and age-related macular degeneration (AMD) Bruch's membrane (BM). METHODS: Retinal pigment epithelium (RPE) cells derived from human embryonic stem cells (hES-RPE) and cultured fetal and aged adult RPE were seeded onto the inner collagenous layer of submacular BM-choroid-sclera explants generated from aged and AMD human donor eyes. Paired explants were cultured in BCEC-CM or CM vehicle. To assess cell behavior after attachment to BM was established, explants were harvested after 21 days in culture. To assess whether sustained exposure to BCEC-CM was necessary for improved cell survival on BM, short exposure to BCEC-CM (3, 7, 14 days) was compared with 21-day exposure. Explants were harvested and evaluated by scanning electron and light microscopy. Extracellular matrix (ECM) deposition after exposure to BCEC-CM was evaluated following RPE cell removal after day 21 on tissue culture dishes or on BM. RESULTS: BCEC-CM significantly enhanced hES-RPE, fetal RPE, and aged adult RPE survival on BM, regardless of submacular pathology. Although shorter BCEC-CM exposure times showed significant improvement in cell survival compared with culture in CM vehicle, longer BCEC-CM exposure times were more effective. BCEC-CM increased RPE ECM deposition on tissue culture plastic and on BM. CONCLUSIONS: The results of this study indicate that RPE survival is possible on AMD BM and offer a method that could be developed for enhancing transplanted cell survival on AMD BM. Increased ECM deposition may account for improved cell survival after culture in BCEC-CM. PMID- 22039245 TI - A novel bisretinoid of retina is an adduct on glycerophosphoethanolamine. AB - PURPOSE: Fluorescent bisretinoid compounds accumulate in retinal pigment epithelial (RPE) cells as a consequence of two processes: random reactions of vitamin A aldehyde in photoreceptor cell outer segments, and phagocytosis of discarded photoreceptor outer segment discs by RPE. The formation of bisretinoid is accentuated in some forms of retinal degeneration. The detection of a novel bisretinoid fluorophore that is a conjugate of all-trans-retinal and glycerophosphoethanolamine is reported. METHODS: Human RPE/choroid, eyes harvested from Abca4 (ATP-binding cassette transporter 4) null mutant mice, and biosynthetic reaction mixtures were analyzed by ultra performance liquid chromatography coupled to mass spectrometry and by nuclear magnetic resonance spectra and spectrofluorometry. RESULTS: A fluorescent compound in mouse eyes and in human RPE/choroid corresponded to the product of the reaction between all trans-retinal and glycerophosphoethanolamine (A2-GPE), as determined on the basis of molecular weight (m/z 746), absorbance (approximately 338,443 nm), and retention time. Nuclear magnetic resonance spectra were consistent with a pyridinium molecule with a glycerophosphate moiety. The emission maximum of A2 GPE was approximately 610 nm. A2-GPE accumulated with age in mouse eyes and was more abundant in Abca4(-/-) mice, a model of recessive Stargardt disease. CONCLUSIONS: To date, several bisretinoids of RPE lipofuscin have been isolated and characterized, and for all of these, formation involves the membrane phospholipid phosphatidylethanolamine. Conversely, the bisretinoid A2-GPE is detected as sn-glycero-3-phosphoethanolamine (GPE) derivatized by two all-trans retinal. The pathways by which A2-GPE may form under conditions of increased availability of all-trans-retinal, for instance in the Abca4(-/-) mouse, are discussed. PMID- 22039246 TI - Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images. AB - PURPOSE: To automatically segment retinal spectral domain optical coherence tomography (SD-OCT) images of eyes with age-related macular degeneration (AMD) and various levels of image quality to advance the study of retinal pigment epithelium (RPE)+drusen complex (RPEDC) volume changes indicative of AMD progression. METHODS: A general segmentation framework based on graph theory and dynamic programming was used to segment three retinal boundaries in SD-OCT images of eyes with drusen and geographic atrophy (GA). A validation study for eyes with nonneovascular AMD was conducted, forming subgroups based on scan quality and presence of GA. To test for accuracy, the layer thickness results from two certified graders were compared against automatic segmentation results for 220 B scans across 20 patients. For reproducibility, automatic layer volumes were compared that were generated from 0 degrees versus 90 degrees scans in five volumes with drusen. RESULTS: The mean differences in the measured thicknesses of the total retina and RPEDC layers were 4.2 +/- 2.8 and 3.2 +/- 2.6 MUm for automatic versus manual segmentation. When the 0 degrees and 90 degrees datasets were compared, the mean differences in the calculated total retina and RPEDC volumes were 0.28% +/- 0.28% and 1.60% +/- 1.57%, respectively. The average segmentation time per image was 1.7 seconds automatically versus 3.5 minutes manually. CONCLUSIONS: The automatic algorithm accurately and reproducibly segmented three retinal boundaries in images containing drusen and GA. This automatic approach can reduce time and labor costs and yield objective measurements that potentially reveal quantitative RPE changes in longitudinal clinical AMD studies. (ClinicalTrials.gov number, NCT00734487.). PMID- 22039247 TI - Doxycycline enhances the inhibitory effects of bevacizumab on corneal neovascularization and prevents its side effects. AB - PURPOSE: To investigate the combination therapeutic effects of topical doxycycline temperature-sensitive hydrogel (DTSH) and bevacizumab on corneal neovascularization (CNV) and corneal wound healing (CWH) and to explore the underlying mechanisms of doxycycline on CNV and CWH. METHODS: Rats were treated with a saline solution, topical DTSH (0.1%), topical bevacizumab (2.5 mg/0.1 mL), or a DTSH and bevacizumab combination. For the bFGF-induced CNV model (n = 15/group), the length and area of CNV were measured on day 7. In the alkali burn model (n = 33/group), the length and area of CNV were determined on days 3, 7, 14, and 21 after alkali burn. The activity of matrix metalloproteinase (MMP)-2 and MMP-9 was determined by a fluorogenic peptide substrate. Western blot, real time PCR, and ELISA were used to analyze the expression of induced nitric oxide synthase (iNOS), VEGF, VEGFRS, MMP-2, MMP-9, and IL-1beta. RESULTS: Combination therapy more effectively inhibited CNV than therapy with topical bevacizumab or DTSH alone. DTSH combined with bevacizumab significantly accelerated delayed CWH caused by topical bevacizumab in the alkali burn model (P = 0.018). Combination therapy showed better inhibitory effects on MMP expression and phosphorylated VEGFR1 and VEGFR2. With DTSH treatment, doxycycline inhibited the activity and expression of MMPs, the expression of VEGF and of phosphorylated VEGFR1 and VEGFR2, and the production of iNOS and IL-1beta in local cornea. CONCLUSIONS: Doxycycline enhances the inhibitory effects of bevacizumab on CNV and prevents its side effects on CWH, possibly by inhibiting the expression and activity of MMPs, the expression of VEGF and of phosphorylated VEGFR1 and VEGFR2, and the production of iNOS and IL-1beta. PMID- 22039248 TI - AAV-mediated gene transfer of human X-linked inhibitor of apoptosis protects against oxidative cell death in human RPE cells. AB - PURPOSE: To determine whether human X-linked inhibitor of apoptosis (XIAP) enhances the survival of cultured human retinal pigment epithelial cells exposed to H(2)O(2). METHODS: ARPE-19 cells were exposed to H(2)O(2) to induce oxidative cell death. Intracellular reactive oxygen species (ROS) were measured using 2',7' dichlorofluorescein diacetate. MTT assay was performed to quantify mitochondrial stress. Cell apoptosis was determined by TUNEL assay. Human XIAP was delivered with bicistronic expression of green fluorescent protein (GFP), using recombinant adeno-associated virus (AAV-XIAP-GFP). The null vector, containing identical sequences but without XIAP, was used as a control (AAV-NULL-GFP). Transduced cells underwent fluorescence-activated cell sorting. XIAP overexpression was examined by immunostaining and Western blot analysis. RESULTS: ARPE-19 cells exposed to 0.25 mM H(2)O(2) for 1 hour showed increased TUNEL staining compared with nonstressed cells (17 +/- 1.4 vs. 1.8 +/- 0.4 cells per 20 * field; P = 0.000006), accompanied by a significant increase in intracellular ROS (207 +/- 46% vs. 100 +/- 9.5%; P = 0.0002). The AAV-XIAP-GFP transduced cells had 11-fold higher XIAP expression than the AAV-NULL-GFP controls (1300 +/- 126% vs. 120 +/- 10%; P = 0.0006). XIAP over-expression significantly reduced the number of apoptotic cells after stress compared with the AAV-NULL-GFP controls (3.2 +/- 0.6 vs. 18 +/- 1.6 cells per 20 * field; P = 0.00003). Mitochondrial stress was reduced by AAV-XIAP-GFP, but did not reach a statistical significance (68 +/- 3.5% vs. 74 +/- 3.8%; P = 0.24). CONCLUSIONS: Overexpression of human XIAP protects ARPE-19 cells against H(2)O(2)-induced oxidative cell death by acting downstream on the apoptotic pathway. XIAP gene therapy using AAV may provide a means of reducing the effect of oxidative stress to RPE cells in age-related macular degeneration. PMID- 22039249 TI - Automated discovery and quantification of image-based complex phenotypes: a twin study of drusen phenotypes in age-related macular degeneration. AB - PURPOSE: Determining the relationships between phenotype and genotype of many disorders can improve clinical diagnoses, identify disease mechanisms, and enhance therapy. Most genetic disorders result from interaction of many genes that obscure the discovery of such relationships. The hypothesis for this study was that image analysis has the potential to enable formalized discovery of new visible phenotypes. It was tested in twins affected with age-related macular degeneration (AMD). METHODS: Fundus images from 43 monozygotic (MZ) and 32 dizygotic (DZ) twin pairs with AMD were examined. First, soft and hard drusen were segmented. Then newly defined phenotypes were identified by using drusen distribution statistics that significantly separate MZ from DZ twins. The ACE model was used to identify the contributions of additive genetic (A), common environmental (C), and nonshared environmental (E) effects on drusen distribution phenotypes. RESULTS: Four drusen distribution characteristics significantly separated MZ from DZ twin pairs. One encoded the quantity, and the remaining three encoded the spatial distribution of drusen, achieving a zygosity prediction accuracy of 76%, 74%, 68%, and 68%. Three of the four phenotypes had a 55% to 77% genetic effect in an AE model, and the fourth phenotype showed a nonshared environmental effect (E model). CONCLUSIONS: Computational discovery of genetically determined features can reveal quantifiable AMD phenotypes that are genetically determined without explicitly linking them to specific genes. In addition, it can identify phenotypes that appear to result predominantly from environmental exposure. The approach is rapid and unbiased, suitable for large datasets, and can be used to reveal unknown phenotype-genotype relationships. PMID- 22039250 TI - Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy. AB - PURPOSE: To establish, using adaptive optics scanning laser ophthalmoscopy (AOSLO), that the retinal parafoveal capillary network is altered before the onset of diabetic retinopathy in adult patients with type 2 diabetes. METHODS: AOSLO videos were acquired in the parafoveal region of one eye from control subjects and from patients with type 2 diabetes and no retinopathy. Detailed images of the parafoveal capillary network were generated with custom motion contrast enhancement algorithms. The combination of AOSLO images and videos enabled the simultaneous assessment of several features of the parafoveal capillary network. Arteriovenous (AV) channels were identified by finding the least tortuous capillary channels connecting terminal arterioles to postcapillary venules. Measures of capillary dropout and capillary hemodynamics were also quantified. RESULTS: The average tortuosity of AV channels was 26% higher in patients with type 2 diabetes when compared with controls, even though there were no signs of diabetic retinopathy in any of the eyes that were assessed (P < 0.05). In addition, the metrics of capillary dropout showed small changes (between 3% and 7%), leukocyte speed 14% lower, and pulsatility 25% higher, but none of these differences was statistically significant. CONCLUSIONS: It is often difficult to find consistent changes in the retinal microvasculature due to large intersubject variability. However, with a novel application of AOSLO imaging, it is possible to visualize parafoveal capillaries and identify AV channels noninvasively. AV channels are disrupted in type 2 diabetes, even before the onset of diabetic retinopathy. PMID- 22039251 TI - New grading criteria allow for earlier detection of geographic atrophy in clinical trials. AB - PURPOSE: To evaluate new grading criteria for geographic atrophy (GA), as detected by annual stereoscopic color fundus photographs and fluorescein angiograms, and to assess whether application of the revised criteria provides earlier identification of GA than previous criteria involving only color fundus photography. METHODS: Annual fundus image sets from 114 CAPT patients who developed GA in the untreated eye during 5 to 6 years of follow-up were reassessed for the presence of GA, using revised grading criteria, in which GA was defined by (1) the presence of hyperfluorescence on fluorescein angiography; and (2) at least one other characteristic indicative of involution of the retinal pigment epithelium (i.e., sharp edges, excavation of the retina, or visible choroidal vessels on either color images or fluorescein angiograms). Reliability and time of initial detection of GA using the revised criteria were assessed. RESULTS: The revised criteria are reliable (97.8% intragrader, 93.3% intergrader agreement) and accurate (false-positive rate, 0.8%) for detecting individual early GA lesions. Using this revised method, individual GA lesions were identified 1-year earlier on average than was possible with criteria used in previous CFP studies. The use of two imaging modalities was more sensitive in detecting GA and its features than either imaging modality alone (P <= 0.0001). CONCLUSIONS: Early GA areas can be reliably identified when defining criteria are based on both color photographs and fluorescein angiograms. These methods can be used to investigate the natural history of GA earlier in the course of disease than previously possible and to facilitate the design of future clinical trials of treatments for GA. (ClinicalTrials.gov number, NCT00000167). PMID- 22039252 TI - Patient-specific computational modeling of keratoconus progression and differential responses to collagen cross-linking. AB - PURPOSE: To model keratoconus (KC) progression and investigate the differential responses of central and eccentric cones to standard and alternative collagen cross-linking (CXL) patterns. METHODS: Three-dimensional finite element models (FEMs) were generated with clinical tomography and IOP measurements. Graded reductions in regional corneal hyperelastic properties and thickness were imposed separately in the less affected eye of a KC patient. Topographic results, including maximum curvature and first-surface, higher-order aberrations (HOAs), were compared to those of the more affected contralateral eye. In two eyes with central and eccentric cones, a standard broad-beam CXL protocol was simulated with 200- and 300-MUm treatment depths and compared to spatially graded broad beam and cone-centered CXL simulations. RESULTS: In a model of KC progression, maximum curvature and HOA increased as regional corneal hyperelastic properties were decreased. A topographic cone could be generated without a reduction in corneal thickness. Simulation of standard 9-mm-diameter CXL produced decreases in corneal curvature comparable to clinical reports and affected cone location. A 100-MUm increase in CXL depth enhanced flattening by 24% to 34% and decreased HOA by 22% to 31%. Topographic effects were greatest with cone-centered CXL simulations. CONCLUSIONS: Progressive hyperelastic weakening of a cornea with subclinical KC produced topographic features of manifest KC. The clinical phenomenon of topographic flattening after CXL was replicated. The magnitude and higher-order optics of this response depended on IOP and the spatial distribution of stiffening relative to the cone location. Smaller diameter simulated treatments centered on the cone provided greater reductions in curvature and HOA than a standard broad-beam CXL pattern. PMID- 22039253 TI - Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. AB - The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph(+)) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (-Y) and 41 patients (3.6%) had ACAs except -Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), -Y, minor- and major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis. PMID- 22039254 TI - A shared gene expression signature in mouse models of EBV-associated and non-EBV associated Burkitt lymphoma. AB - The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional profiles of tumor cells from LMP2A/lambda-MYC and lambda-MYC mice are strikingly similar, with fewer than 20 genes differentially expressed. We evaluated the functional significance of one of the most interesting differentially expressed genes, Egr1, and found that it was not required for acceleration of tumor onset by LMP2A. Our studies demonstrate the remarkable ability of LMP2A to affect the pretumor B-cell phenotype and tumorigenesis without substantially altering gene expression in tumor cells. PMID- 22039255 TI - Regulation of murine hematopoietic stem cell quiescence by Dmtf1. AB - The cell-cycle status of hematopoietic stem cells (HSCs) is tightly regulated, most likely to balance maintenance of stem-cell status through quiescence and expansion/differentiation of the hematopoietic system. Tumor-suppressor genes (TSGs), with their cell cycle-regulatory functions, play important roles in HSC regulation. The cyclin-D binding myb-like transcription factor 1 (Dmtf1) was recently recognized as a TSG involved in human cancers by repressing oncogenic Ras/Raf signaling. However, the role of Dmtf1 in the hematopoietic system is entirely unknown. In the present study, we demonstrate that Dmtf1 regulates HSC function under both steady-state and stress conditions. Dmtf1(-/-) mice showed increased blood cell counts in multiple parameters, and their progenitor cells had increased proliferation and accelerated cell-cycle progression. In addition, long-term HSCs from Dmtf1(-/-) mice had a higher self-renewal capacity that was clearly demonstrated in secondary recipients in serial transplantation studies. Dmtf1(-/-) BM cells showed hyper proliferation after 5-fluorouracil-induced myeloablation. Steady-state expression and Induction of CDKN1a (p21) and Arf were impaired in HSCs from Dmtf1(-/-) mice. The function of Dmtf1 was mediated by both Arf-dependent and Arf-independent pathways. Our results implicate Dmtf1 in the regulation of HSC function through novel cell cycle-regulatory mechanisms. PMID- 22039256 TI - Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study. AB - Patients with chronic myeloproliferative neoplasms, including essential thrombocythemia (ET), polycythemia vera (PV), and chronic myeloid leukemia (CML), are at increased risk of new hematologic malignancies, but their risk of nonhematologic malignancies remains unknown. In the present study, we assessed the risk of both types of malignancies after an ET, PV, or CML diagnosis. We linked 2 population-based nationwide registries, the Danish National Registry of Patients, covering all Danish hospitals and the Danish Cancer Registry, and assessed subsequent cancer risk in a cohort of all 7229 patients diagnosed with a chronic myeloproliferative neoplasm during 1977-2008. We compared the incidence of subsequent cancer in this cohort with that expected on the basis of cancer incidence in the general population (standardized incidence ratio). Overall, ET, PV, and CML patients were at increased risk of developing both new hematologic and nonhematologic cancers. The standardized incidence ratio for developing a nonhematologic cancer was 1.2 (95% confidence interval [95% CI]): 1.0-1.4) for patients with ET, 1.4 (95% CI: 1.3-1.5) for patients with PV, and 1.6 (95% CI: 1.3-2.0) for patients with CML. We conclude that patients with chronic myeloproliferative neoplasms are at increased risk of developing a new malignant disease. PMID- 22039257 TI - Bioengineered human vascular networks transplanted into secondary mice reconnect with the host vasculature and re-establish perfusion. AB - The ability to form anastomoses with the host circulation is essential for vascular networks incorporated within cell-seeded bioengineered tissues. Here, we tested whether and how rapidly human endothelial colony forming cell (ECFC)/mesenchymal progenitor cell (MPC)-derived bioengineered vessels, originally perfused in one mouse, could become reperfused in a secondary mouse. Using in vivo labeling with a systemically injected mixture of human- and murine specific lectins, we demonstrate that ECFC/MPC blood vessels reconnect and are perfused at day 3 after transplantation. Furthermore, we quantified the longitudinal change in perfusion volume in the same implants before and after transplantation using contrast-enhanced micro-ultrasonic imaging. Perfusion was restored at day 3 after transplantation and increased with time, suggesting an important new feature of ECFC/MPC blood vessels: the bioengineered vessels can reconnect with the vasculature when transplanted to a new site. This feature extends the potential applications of this postnatal progenitor cell-based technology for transplantable large tissue-engineered constructs. PMID- 22039258 TI - Blood consult: treating del(5q) myelodysplastic syndromes. PMID- 22039259 TI - Publication bias is present in blood and marrow transplantation: an analysis of abstracts at an international meeting. AB - Publication bias is the preferential publication of research with positive results, and is a threat to the validity of medical literature. Preliminary evidence suggests that research in blood and marrow transplantation (BMT) lacks publication bias. We evaluated publication bias at an international conference, the 2006 Center for International Blood and Marrow Transplant Research (CIBMTR)/American Society for Blood and Marrow Transplantation (ASBMT) "tandem" meeting. All abstracts were categorized by type of research, funding status, number of centers, sample size, and direction of the results. Publication status was then determined for the abstracts by searching PubMed. Of 501 abstracts, 217 (43%) were later published as complete manuscripts. Abstracts with positive results were more likely to be published than those with negative or unstated results (P = .001). Furthermore, positive studies were published in journals with a mean impact factor of 6.92, whereas journals in which negative/unstated studies were published had an impact factor of only 4.30 (P = .02). We conclude that publication bias exists in the BMT literature. Full publication of research, regardless of direction of results, should be encouraged and the BMT community should be aware of the existence of publication bias. PMID- 22039260 TI - Prognostic and therapeutic implications of minimal residual disease detection in acute myeloid leukemia. AB - The choice of either induction or postremission therapy for adults with acute myeloid leukemia is still largely based on the "one size fits all" principle. Moreover, pretreatment prognostic parameters, especially chromosome and gene abnormalities, may fail in predicting individual patient outcome. Measurement of minimal residual disease (MRD) is nowadays recognized as a potential critical tool to assess the quality of response after chemotherapy and to plan postremission strategies that are, therefore, driven by the individual risk of relapse. PCR and multiparametric flow cytometry have become the most popular methods to investigate MRD because they have been established as sensitive and specific enough to allow MRD to be studied serially. In the present review, we examine the evidence supporting the appropriateness of incorporating MRD detection into the AML risk assessment process. A comprehensive prognostic algorithm, generated by combining pretreatment cytogenetics/genetics and posttreatment MRD determination, should promote advances in development of personalized therapeutic approaches. PMID- 22039261 TI - Lymph node B lymphocyte trafficking is constrained by anatomy and highly dependent upon chemoattractant desensitization. AB - B lymphocyte recirculation through lymph nodes (LNs) requires crossing endothelial barriers and chemoattractant-triggered cell migration. Here we show how LN anatomy and chemoattractant receptor signaling organize B lymphocyte LN trafficking. Blood-borne B cells predominately used CCR7 signaling to adhere to high endothelial venules (HEVs). New B cell emigrants slowly transited the HEV perivenule space, and thereafter localized nearby, avoiding the follicle. Eventually, the newly arrived B cells entered the basal portion of the follicle gradually populating it. In contrast, newly arriving activated B cells rapidly crossed HEVs and migrated toward the lymph node follicle. During their LN residency, recirculating B cells reacquired their sphingosine-1 phospate receptor 1 (S1P1) receptors and markedly attenuated their sensitivity to chemokines. Eventually, the B cells exited the LN follicle by entering the cortical lymphatics or returning to the paracortical cords. Upon entering the lymph, the B cells lost their polarity, down-regulated their S1P1 receptors, and subsequently strongly up-regulated their sensitivity to chemokines. These results are summarized in a model of homeostatic trafficking of B cells through LNs. PMID- 22039262 TI - The redox-sensitive transcription factor Nrf2 regulates murine hematopoietic stem cell survival independently of ROS levels. AB - Several studies have found that high levels of reactive oxidative species (ROS) are associated with stem cell dysfunction. In the present study, we investigated the role of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, and found that it is required for hematopoietic stem progenitor cell (HSPC) survival and myeloid development. Although the loss of Nrf2 leads to increased ROS in most tissues, basal ROS levels in Nrf2-deficient (Nrf2(-/-)) BM were not elevated compared with wild type. Nrf2(-/-) HSPCs, however, had increased rates of spontaneous apoptosis and showed decreased survival when exposed to oxidative stress. Nrf2(-/-) BM demonstrated defective stem cell function, as evidenced by reduced chimerism after transplantation that was not rescued by treatment with the antioxidant N acetyl cysteine. Gene-expression profiling revealed that the levels of prosurvival cytokines were reduced in Nrf2(-/-) HSPCs. Treatment with the cytokine G-CSF improved HSPC survival after exposure to oxidative stress and rescued the transplantation defect in Nrf2(-/-) cells despite increases in ROS induced by cytokine signaling. These findings demonstrate a critical role for Nrf2 in hematopoiesis and stem cell survival that is independent of ROS levels. PMID- 22039263 TI - Engineering pro-angiogenic peptides using stable, disulfide-rich cyclic scaffolds. AB - Fragments from the extracellular matrix proteins laminin and osteopontin and a sequence from VEGF have potent proangiogenic activity despite their small size (< 10 residues). However, these linear peptides have limited potential as drug candidates for therapeutic angiogenesis because of their poor stability. In the present study, we show that the therapeutic potential of these peptides can be significantly improved by "grafting" them into cyclic peptide scaffolds. Momordica cochinchinensis trypsin inhibitor-II (MCoTI-II) and sunflower trypsin inhibitor-1 (SFTI-1), naturally occurring, plant-derived cyclic peptides of 34 and 14 residues, respectively, were used as scaffolds in this study. Using this approach, we have designed a peptide that, in contrast to the small peptide fragments, is stable in human serum and at nanomolar concentration induces angiogenesis in vivo. This is the first report of using these scaffolds to improve the activity and stability of angiogenic peptide sequences and is a promising approach for promoting angiogenesis for therapeutic uses. PMID- 22039264 TI - Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. AB - The genetic lesions identified in chronic lymphocytic leukemia (CLL) do not entirely recapitulate the disease pathogenesis and the development of serious complications, such as chemorefractoriness. While investigating the coding genome of fludarabine-refractory CLL, we observed that mutations of SF3B1, encoding a splicing factor and representing a critical component of the cell spliceosome, were recurrent in 10 of 59 (17%) fludarabine-refractory cases, with a frequency significantly greater than that observed in a consecutive CLL cohort sampled at diagnosis (17/301, 5%; P = .002). Mutations were somatically acquired, were generally represented by missense nucleotide changes, clustered in selected HEAT repeats of the SF3B1 protein, recurrently targeted 3 hotspots (codons 662, 666, and 700), and were predictive of a poor prognosis. In fludarabine-refractory CLL, SF3B1 mutations and TP53 disruption distributed in a mutually exclusive fashion (P = .046). The identification of SF3B1 mutations points to splicing regulation as a novel pathogenetic mechanism of potential clinical relevance in CLL. PMID- 22039265 TI - Tryptophan catabolism is associated with acute GVHD after human allogeneic stem cell transplantation and indicates activation of indoleamine 2,3-dioxygenase. AB - Induction of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation along the kynurenine pathway, acts as a potent immunoregulatory loop. To address its role in human allogeneic stem cell transplantation, we measured major tryptophan metabolites, such as quinolinic acid and kynurenine, in serial urine specimens from 51 patients by liquid chromatography-tandem mass spectrometry. Samples were collected between admission and day 90 after transplantation, and metabolite levels were correlated with early clinical events and outcome. In selected patients, IDO gene expression was assessed by quantitative RT-PCR in intestinal biopsies. Surviving patients had significantly lower metabolite levels on days 28, 42, and 90, respectively, compared with patients dying of GVHD and associated complications (n = 10). Kynurenine levels were directly correlated with severity and clinical course of GVHD: Mean urinary quinolinic acid levels were 4.5 +/- 0.3 MUmol/mmol creatinine in the absence of acute GVHD, 8.0 +/- 1.1 MUmol/mmol creatinine for GVHD grade 1 or 2, and 13.5 +/- 2.7 MUmol/mmol creatinine for GVHD grade 3 or 4 (P < .001), respectively. GVHD-dependent induction of IDO was further suggested by increased expression of IDO mRNA in intestinal biopsies from patients with severe GVHD. Our data indicate reactive release of kynurenines in GVHD-associated inflammation. PMID- 22039266 TI - IL-21 is the primary common gamma chain-binding cytokine required for human B cell differentiation in vivo. AB - SCID resulting from mutations in IL2RG or JAK3 is characterized by lack of T and natural killer cells; B cells are present in normal number, but antibody responses are defective. Hematopoietic cell transplantation (HCT) is curative for SCID. However, B-cell dysfunction persists in a substantial proportion of patients. We hypothesized that impaired B-cell responses after HCT in IL2RG/JAK3 deficiency results from poor donor B-cell engraftment and defective gammac dependent cytokine signaling in host B cells. To test this, and to identify which gammac cytokine(s) is critical for humoral immunity, we studied 28 transplanted patients with IL2RG/JAK3 deficiency. Lack of donor B-cell engraftment associated with persistent humoral dysfunction and significantly reduced memory B cells. B cell proliferation induced by CD40L alone or together with CpG, anti-Ig, IL-4, IL 10, or IL-13 was comparable in healthy controls and in post-HCT SCID patients, irrespective of their chimerism status. However, in vitro stimulation with CD40L/IL-21 induced B-cell proliferation, plasmablast differentiation, and antibody secretion in patients with donor B cells, but not in patients with autologous B cells. These data imply that IL-21-mediated signaling is critical for long-lived humoral immunity and to restore antibody responses in IL2RG/JAK3 deficient patients after HCT. Furthermore, in vitro stimulation with CD40L/IL-21 can predict in vivo B-cell immunity in IL2RG/JAK3 SCID after transplantation. PMID- 22039267 TI - Value of ANCA measurements during remission to predict a relapse of ANCA associated vasculitis--a meta-analysis. AB - OBJECTIVE: The value of repeated ANCA measurements among patients with an established diagnosis of ANCA-associated vasculitis (AAV) remains controversial. The aim of this study was to explore whether either of the two distinct patterns of ANCA values during remission, a rise in ANCA or persistently positive ANCA, predicted future relapse. METHODS: MEDLINE and EMBASE searches were performed. Studies with at least 10 subjects with AAV from which both sensitivity and specificity of a rise in ANCA and/or persistent ANCA for future disease relapse could be calculated were included. Likelihood ratios were calculated for each study and pooled to arrive at summary estimates. I(2)-values were calculated as a measure of heterogeneity and meta-regression was used to explore sources of heterogeneity. RESULTS: Nine articles on a rise in ANCA and nine articles on persistent ANCA were included. The summary estimates for positive likelihood ratio (LR(+)) and negative likelihood ratio (LR(-)) of a rise in ANCA during remission on subsequent relapse of disease were 2.84 (95% CI 1.65, 4.90) and 0.49 (95% CI 0.27, 0.87), respectively. The summary estimates for LR(+) and LR(-) of persistent ANCA during remission for subsequent disease relapse were 1.97 (95% CI 1.43, 2.70) and 0.73 (95% CI 0.50, 1.06), respectively. There was substantial between-study heterogeneity, which was partially explained by the frequency of ANCA measurements. CONCLUSION: Among patients with AAV, a rise in or persistence of ANCA during remission is only modestly predictive of future disease relapse. There is limited use to serial ANCA measurements during disease remission to guide treatment decisions for individual patients with AAV. PMID- 22039268 TI - Systemic lupus erythematosus risk factors for coronary artery calcifications. AB - OBJECTIVE: Premature atherosclerosis in patients with SLE is partially explained by traditional risk factors; therefore, we aimed to identify lupus-related risk factors for coronary artery calcifications. METHODS: An inception cohort of 139 lupus patients (93% females) was screened for coronary artery calcifications using Multidetector CT, after 5.1 years of follow-up. Clinical and immunological variables and cardiovascular risk factors were assessed longitudinally. Also, 100 age- and sex-matched healthy subjects were studied. Correlates for calcifications were analysed in lupus patients, including levels of lipids and inflammatory molecules in samples obtained at enrolment, mid-term follow-up and at screening. RESULTS: At enrolment, lupus patients were 27.2 (9.1) years of age and with a disease duration of 5.4 (3.8) months. Calcifications were detected in 7.2% of patients and 1% of controls [unadjusted odds ratio (OR) 7.7, 95% CI 1.05, 336.3, P = 0.02]. In lupus, calcifications were detected since the age of 23 years and from 3 years of diagnosis. Patients with calcifications were older, post menopausal, and had higher levels of serum apolipoprotein B and Framingham risk scores (P < 0.05). Lupus-related factors identified included age at diagnosis, IgG aCLs, cumulative lupus activity, length of moderate/severe activity and cumulative dose of prednisone and CYC (P < 0.05). Use of anti-malarials was protective (P = 0.006). Logistic regression analysis showed as predictors of calcification: disease duration (OR 15.1, 95% CI 2.6, 87.2), age at enrolment (OR 8.5, 95% CI 1.7, 43.0) and SLEDAI 2000 update (SLEDAI-2K) mean area under the curve (OR 12.3, 95% CI 2.5, 61.8). Longitudinal analyses of lipids and inflammatory molecules did not differ between patients. CONCLUSIONS: Disease activity is a potentially modifiable risk factor for coronary artery calcifications in SLE. Therefore, management of traditional risk factors plus tight control of lupus activity, including the use of anti-malarials, is recommended. PMID- 22039269 TI - Treatment of trigger finger: randomized clinical trial comparing the methods of corticosteroid injection, percutaneous release and open surgery. AB - OBJECTIVE: The aim of this study is to evaluate the effectiveness of CS injection, percutaneous pulley release and conventional open surgery for treating trigger finger in terms of cure, relapse and complication rates. METHODS: One hundred and thirty-seven patients with a total of 150 fingers were randomly assigned and allocated into one of the treatment groups, with treatments allocated into 150 opaque and sealed envelopes. We included patients >15 years of age with a trigger on any finger of the hand (Types II-IV) and used a minimum follow-up time of 6 months. The primary outcome measures were cures, relapses and failures. RESULTS: Forty-nine patients were assigned to the conservative group to undergo CS injections, whereas 45 and 56 were assigned to undergo percutaneous release and outpatient open surgery, respectively. The trigger cure rate for patients in the injection method group was 57%, and wherever necessary, two injections were administered, which increased the cure rate to 86%. For the percutaneous and open release methods, remission of the trigger was achieved in all cases. CONCLUSIONS: The percutaneous and open surgery methods displayed similar effectiveness and proved superior to the conservative CS method regarding the trigger cure and relapse rates. Trial registration. Current Controlled Trials, http://www.controlled-trials.com/, ISRCTN19255926. PMID- 22039270 TI - Radon progeny in hydrometeors at the earth's surface. AB - During atmospheric thermal inversions, dew and hoarfrost concentrate gamma emitting radionuclides of the short-lived (222)Rn progeny ((214)Pb and (214)Bi), causing an increase in the total natural gamma background from the ground. To highlight this phenomenon, a volcanic zone of high (222)Rn flux was studied during the winter season 2010-11. High-specific short-lived radon progeny activities up to 122 Bq g(-1) were detected in hydrometeors forming at the earth's surface (ESHs), corresponding to a mean increase of up to 17 % of the normal gamma background value. A theoretical model, depending on radon flux from soil and predicting the radon progeny concentrations in hydrometeors forming at the ESHs is presented. The comparison between model and field data shows a good correspondence. Around nuclear power plants or in nuclear facilities that use automatic NaI or CsI total gamma spectroscopy systems for monitoring radioactive contamination, hydrometeors forming at the ESHs in sites with a high radon flux could represent a relevant source of false alarms of radioactive contamination. PMID- 22039271 TI - Organ dose evaluation for multi-slice spiral CT scans based on China Sichuan chest anthropomorphic phantom measurements. AB - The authors measured organ radiation doses during multi-slice computed tomography (MSCT) chest scans using a China Sichuan anthropomorphic phantom (CDP-1C). Chest CT images from live volunteers based on automatic tube current modulation (ATCM) techniques were similar to those obtained using the CDP-1C phantom, indicating that the phantom accurately modelled the anatomic structure and X-ray absorbance of the human torso. Indeed, attenuation values differed by <5%. Organ radiation doses were measured using thermoluminescence dosemeters in the CDP-1C. With increased noise index, the CT dose index, the dose-length product and the average organ dose all decreased. Thus, the CDP-1C phantom can also assess dose levels during CT examinations in Chinese patients. The noise index (based on ATCM techniques) should be set to 8.5 or higher to reduce X-ray exposure while maintaining appropriate resolution for diagnosis. PMID- 22039272 TI - Management of ankle fractures. PMID- 22039273 TI - Centres of health innovation are established in Africa to promote research and development. PMID- 22039274 TI - Mcl-1 reduction due to caspase-dependent cleavage during endoplasmic reticulum stress-induced apoptosis. PMID- 22039275 TI - Disulphide linkage in mouse ST6Gal-I: determination of linkage positions and mutant analysis. AB - All cloned sialyltransferases from vertebrates are classified into four subfamilies and are characterized as having type II transmembrane topology. The catalytic domain has highly conserved motifs known as sialylmotifs. Besides sialylmotifs, each family has several unique conserved cysteine (Cys) residues mainly in the catalytic domain. The number and loci of conserved amino acids, however, differ with each subfamily, suggesting that the conserved Cys-residues and/or disulphide linkages they make may contribute to linkage specificity. Using Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF)-mass spectrometry, the present study performed disulphide linkage analysis on soluble mouse ST6Gal-I, which has six Cys-residues. Results confirmed that there were no free Cys-residues, and all six residues contributed to disulphide linkage formation, C(139)-C(403), C(181)-C(332) and C(350)-C(361). Study of single amino acid-substituted mutants revealed that the disulphide linkage C(181)-C(332) was necessary for molecular expression of the enzyme, and that the disulphide linkage C(350)-C(361) was necessary for enzyme activity. The remaining disulphide linkage C(139)-C(403) was not necessary for enzyme expression or for activity, including substrate specificity. Crystallographic study of pig ST3Gal I has recently been reported. Interestingly, the loci of disulphide linkages in ST6Gal-I differ from those in ST3Gal I, suggesting that the linkage specificity of sialyltransferase may results from significant structural differences, including the loci of disulphide linkages. PMID- 22039276 TI - Biological meaning of DNA compositional biases evaluated by ratio of membrane proteins. AB - Membrane spanning regions can be used as markers for studying the robustness of biologically important units of proteins against evolutionary change (R. Sawada and S. Mitaku, Genes to Cells, 2010). We carried out computational experiments of extensive DNA mutations on the assumption of constant GC content or constant codon positional nucleotide biases. Randomized sequences were evaluated by membrane protein prediction systems SOSUI and SOSUIsignal. When all amino acid sequences from the total real genomes of 538 prokaryotes were analysed, ratios of membrane proteins to all genes in the total genomes were almost constant around a ratio of 22% with a standard deviation of 1.56. When the nucleotide sequences were randomized, keeping only the GC contents constant, the ratios of membrane proteins became highly diverse with a standard deviation of 10.1. When the codon positional nucleotide biases were taken into account; however, the diverse ratios of membrane proteins converged to a value of ~25% with a standard deviation of 3.55. These results suggest that codon compositional biases play an important role in the evolution of prokaryotes for maintaining a constant ratio of membrane proteins. Further detailed analysis suggested that non-uniform nucleotide compositional biases at the terminal regions are the reason for the small but significant deviation. PMID- 22039277 TI - Toshiaki Osawa: biochemistry of lectins and their applications in immunochemistry and cellular biology. AB - Lectins are proteins that agglutinate cells and exhibit an antibody like, sugar binding specificity. Professor Toshiaki Osawa has discovered, purified and characterized many plant lectins that display diverse biological activities. Using lectins as biochemical tools, he developed methods to determine the biochemical structures of glycoprotein glycans that react with lectins; separated and characterized glycoproteins and cell populations; analysed the mechanisms by which lectins activate cells; and characterized several cytokines produced by immune cells stimulated by lectins. The studies on lectins, the field he took strong leadership, developed into an essential hub of the biology of multicellular organisms. PMID- 22039278 TI - Shigeru Tsuiki: a pioneer in the research fields of complex carbohydrates and protein phosphatases. AB - Dr Tsuiki made three major contributions during his illustrious career as a biochemist. First, he developed the procedure for mucin isolation from bovine submaxillary glands. His work became the basis for mucin biochemistry. Second, he identified four distinct molecular species of mammalian sialidase. Subsequent studies based on his work led to the discovery that sialidase plays a unique role as an intracellular signalling factor involved in the regulation of a variety of cellular functions. Finally, he established the molecular basis for the diversity of mammalian protein phosphatases through protein purification and molecular cloning. His work prompted the functional studies of protein phosphatases. PMID- 22039279 TI - Best practice in primary care pathology: review 13. AB - This 13th best practice review examines tumour marker requesting primary care situations. The review is presented in question--answer format, referenced for each question. This review considers carcinoembryonic antigen carbohydrate antigen 15-3 (Ca15-3) and carbohydrate antigen 19-9 (Ca19-9). The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They will be updated periodically to take account of new information. PMID- 22039280 TI - Change in meticillin-resistant Staphylococcus aureus clones at a tertiary care hospital in the United Arab Emirates over a 5-year period. AB - AIMS: Meticillin-resistant Staphylococcus aureus (MRSA) strains isolated in Tawam Hospital, a tertiary care hospital in the United Arab Emirates, were examined in order to understand the reasons for a doubling of its incidence between 2003 and 2008 while maintaining the same infection control measures. METHODS: All consecutive non-duplicate clinically relevant MRSA isolates recovered between January and December 2003 and between May and October 2008 were studied. The antibiotic susceptibility, pulsed field gel electrophoresis, toxin gene, staphylococcal cassette chromosome mec (SCCmec), spa, agr and multilocus sequence types of the strains were tested. RESULTS: In 2003, typical healthcare-associated (HA-MRSA) genotypes (ST239-MRSA-III, ST22-MRSA-IV and ST5-MRSA-II) represented the majority (61.5%) of the isolates. By 2008 this pattern had changed and clonal types considered as community-associated (CA) MRSA comprised 73.1% of the strains with ST80-MRSA-IV, ST5-MRSA-IV and ST1-MRSA with non-typable SCCmec types being the most frequent. However, further epidemiological investigations showed that only one-third of the CA-MRSA infections were actually acquired in the community, indicating that CA-MRSA clones have entered and spread within the hospital. CONCLUSIONS: The emergence of CA-MRSA clones with subsequent entry to and spread within the hospital has contributed to the increasing incidence of MRSA observed in Tawam Hospital and probably also in other hospitals in the UAE. PMID- 22039281 TI - The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC. AB - The majority of patients with non-small-cell lung cancer (NSCLC) present with advanced disease, with targeted therapies providing some improvement in clinical outcomes. The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. Tyrosine kinase inhibitors (TKIs), which target the EGFR TK domain, have proven to be an effective treatment strategy; however, patient responses to treatment vary considerably. Therefore, the identification of patients most likely to respond to treatment is essential to optimise the benefit of TKIs. Tumour-associated activating mutations in EGFR can identify patients with NSCLC who are likely to have a good response to TKIs. Nonetheless, the majority of patients relapse within a year of starting treatment. Studies of tumours at relapse have demonstrated expression of a T790M mutation in exon 20 of the EGFR TK domain in approximately 50% of cases. Although conferring resistance to reversible TKIs, these patients may remain sensitive to new-generation irreversible/pan-erb inhibitors. A number of techniques have been employed for genotypic assessment of tumour-associated DNA to identify EGFR mutations, each of which has advantages and disadvantages. This review presents an overview of the current methodologies used to identify such molecular markers. Recent developments in technology may make the monitoring of changes in patients' tumour genotypes easier in clinical practice, which may enable patients' treatment regimens to be tailored during the course of their disease, potentially leading to improved patient outcomes. PMID- 22039282 TI - Diagnosis of breast lesions: fine-needle aspiration cytology or core needle biopsy? A review. AB - Diagnosis of breast lesions is routinely performed by the triple assessment of a specialised surgeon, radiologist and pathologist. In this setting, fine-needle aspiration cytology (FNAC) and core needle biopsy (CNB) are the current methods of choice for pathological diagnosis, both with their specific advantages and limitations. Evidence-based literature discussing which of both modalities is preferable in breast lesion diagnosis is sparse and there is no consensus among different specialised breast cancer centres. This study reviews FNAC and CNB for diagnosing breast lesions, comparing methodological issues, diagnostic performance indices, possibilities for additional prognostic and predictive tests and cost effectiveness. Overall, CNB achieved better sensitivity and specificity especially in those lesions that were not definitively benign or malignant, non palpable and/or calcified lesions. Although FNAC is easier to perform, interpretation requires vast experience and even then, it is more often inconclusive requiring additional CNB. The authors conclude that overall CNB is to be preferred as a diagnostic method. PMID- 22039283 TI - LMP1 expression is positively associated with metastasis of nasopharyngeal carcinoma: evidence from a meta-analysis. AB - OBJECTIVE: Latent membrane protein 1 (LMP1) is an oncogene of Epstein-Barr virus (EBV). Although EBV is associated with 90% of nasopharyngeal carcinoma (NPC), the reported detectable expression rates of LMP1 determined by current techniques were from 50% to 80%. This study evaluates the association of LMP1 expression with metastasis in NPC. METHODS: Data from published case-control studies on LMP1 expression and metastasis in NPC were collected up to 30 March 2011. The databases of Pubmed, Medline, Embase, Chinese National Knowledge Infrastructure and the Cochrane Library were searched with keywords 'LMP1 or latent membrane protein 1', 'NPC or nasopharyngeal carcinoma' and 'metastasis' to identify articles published in English or Chinese. Review manager V.5.0.24 software was applied for calculating OR and corresponding 95% CI and for statistical analysis. The combined OR and 95% CI for the cumulative metastasis rate in the LMP1 expression cases versus those in the LMP1-negative cases were estimated by using fixed-effects and random-effects models. RESULTS: 718 cases from 12 articles, including 403 cases with LMP1 expression and 315 cases without LMP1 expression, were reviewed. The cumulative metastasis rates were 66.75% (269/403) in cases with LMP1 expression and 46.98% (148/315) in those without LMP1 expression. The combined OR for the cumulative metastasis rates were 1.98 (95% CI 1.38 to 2.837) in the fixed-effects model and 2.27 (95% CI 1.10 to 4.69) in the random-effects model. CONCLUSION: LMP1 expression is positively associated with metastasis in NPC, thus LMP1 detection in primary NPC might be an effective and feasible means to predict metastasis. PMID- 22039284 TI - Authors' response - the prognostic benefits of routine staining with elastica to increase detection of venous invasion in colorectal cancer specimens. PMID- 22039285 TI - Measurement of folate. PMID- 22039286 TI - Detection of HER2 and Topo 2 in breast cancers: comparison between MLPA and FISH approaches. AB - A significant proportion of breast cancers with HER2 amplification show simultaneous amplification or deletion of Topo 2. Amplification of Topo 2 may lead to the overexpression of the Topo 2 protein and ultimately to hypersensitivity to Topo 2 inhibitors. HER2 and Topo 2 gene status in breast cancer patients has been determined in several studies using immunohistochemistry, florescence in situ hybridisation (FISH) and multiplex ligation-dependent probe amplification (MLPA). Although comparisons of FISH and MLPA have been reported for HER2, it is believed that there are no similar studies for Topo 2. In this study, HER2 and Topo 2 were analysed by MLPA and FISH. There was a high agreement between the two approaches, although MLPA was easier to perform and cheaper than FISH. In conclusion, MLPA is a fast and accurate quantitative method to detect HER2 and Topo 2 amplification, and could be considered a good alternative to FISH. PMID- 22039287 TI - The last time. PMID- 22039288 TI - Coordinated expression of oestrogen and androgen receptors in HER2-positive breast carcinomas: impact on proliferative activity. AB - AIMS: Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are aggressive neoplasms associated with a variable response to systemic therapies. Therefore, the identification of biomarkers to better characterise this heterogeneity would improve treatment efficacy. The aim of this study was to evaluate the influence of androgen receptor (AR) and oestrogen receptor (ER) on clinicopathological features in a series of HER2-positive breast carcinomas. METHODS: A total of 104 carcinomas were selected and reviewed. Immunohistochemical studies for ER, progesterone receptor and Ki-67 were analysed on tumour whole histological sections. AR expression was analysed on samples represented on tissue microarrays. According to steroid receptor expression, cases were classified into three groups: AR positive/ER positive (48 cases), AR positive/ER negative (41 cases) and AR negative/ER negative (13 cases). RESULTS: AR-positive tumours corresponded to 89 (85.6%) of 104 carcinomas. AR-positive carcinomas were associated with a higher frequency of ER and progesterone receptor co-expression and lower proliferative activity determined by the expression of Ki-67. AR-negative carcinomas were more often high grade. The group of AR-positive/ER-negative carcinomas was associated with the highest frequency of apocrine morphological features. The group of AR-negative/ER-negative carcinomas was associated with the highest proliferative activity and the highest frequency of high histological and nuclear grade. The lowest frequency of high grade tumours and the lowest proliferative activity were seen among tumours with expression of both receptors. CONCLUSIONS: These results suggest that co expression of AR and ER can provide a protective effect based on phenotypical presentation of HER2-positive carcinomas. Furthermore, lack of both steroid hormone receptors characterises the most aggressive phenotype. PMID- 22039289 TI - Pharmacokinetics and safety of coadministered oseltamivir and rimantadine in healthy volunteers: an open-label, multiple-dose, randomized, crossover study. AB - Preclinical data suggest increased antiviral activity and less viral resistance when neuraminidase inhibitors and adamantanes are used in combination to harness the complementary effects of their different mechanisms of action. Healthy volunteers were randomized to 5-day oral treatment with oseltamivir 75 mg or rimantadine 100 mg twice daily as monotherapy or to combination treatment. Each participant received all 3 regimens in 1 of 6 treatment sequences, with a minimum of 7 days' washout between periods. Final follow-up was 10 to 14 days after the final dose. Drug exposure, elimination, safety, and tolerability were assessed. There were no clinically relevant differences in 12-hour areas under the concentration-time curves of drug in plasma or peak plasma drug concentrations with combination versus monotherapy. Elimination half-life was unaffected by coadministration. There were no safety/tolerability concerns. One case of vomiting and 1 of paresthesia were considered remotely related to combination treatment, and 1 episode of toothache and 1 of acne were considered unrelated. There were no serious adverse events and no deaths. Combination therapy with oseltamivir and rimantadine at recommended dosages in adults had no discernible effect on the pharmacokinetics of either drug and raised no tolerability issues. PMID- 22039290 TI - Armodafinil and modafinil in patients with excessive sleepiness associated with shift work disorder: a pharmacokinetic/pharmacodynamic model for predicting and comparing their concentration-effect relationships. AB - Armodafinil, the longer lasting R-isomer of racemic modafinil, improves wakefulness in patients with excessive sleepiness associated with shift work disorder (SWD). Pharmacokinetic studies suggest that armodafinil achieves higher plasma concentrations than modafinil late in a dose interval following equal oral doses. Pooled Multiple Sleep Latency Test (MSLT) data from 2 randomized, double blind, placebo-controlled trials in 463 patients with SWD, 1 with armodafinil 150 mg/d and 1 with modafinil 200 mg/d (both administered around 2200 h before night shifts), were used to build a pharmacokinetic/pharmacodynamic model. Predicted plasma drug concentrations were obtained by developing and applying a population pharmacokinetic model using nonlinear mixed-effects modeling. Armodafinil 200 mg produced a plasma concentration above the EC(50) (4.6 ug/mL) for 9 hours, whereas modafinil 200 mg did not exceed the EC(50). Consequently, armodafinil produced greater increases in predicted placebo-subtracted MSLT times of 0.5-1 minute (up to 10 hours after dosing) compared with modafinil. On a milligram-to-milligram basis, armodafinil 200 mg consistently increased wakefulness more than modafinil 200 mg, including times late in the 8-hour shift. PMID- 22039291 TI - The pharmacokinetic interaction between an oral contraceptive containing ethinyl estradiol and norethindrone and the HCV protease inhibitor telaprevir. AB - BACKGROUND: Telaprevir is a hepatitis C virus protease inhibitor that is both a substrate and an inhibitor of CYP3A. STUDY DESIGN: The effect of steady-state telaprevir (administered 750 mg every 8 hours) on the steady-state pharmacokinetics of ethinyl estradiol (EE) and norethindrone (NE) was evaluated in 24 healthy women receiving oral contraceptives (OC) containing 0.5 mg NE and 0.035 mg EE for at least 3 months at the time of screening. This was a phase 1, open-label, single-center, nonrandomized study that included a cycle 1 (OC only for 21 days, followed by no OC for 7 days), cycle 2 (OC plus telaprevir for 21 days, followed by telaprevir alone for 7 days), and a follow-up period. RESULTS: When administration with or without telaprevir was compared, the least-squares mean ratios (90% confidence limits) for EE were 0.74 (0.68; 0.80) for C(max), 0.67 (0.63; 0.71) for C(min), and 0.72 (0.69; 0.75) for AUC; neither NE nor telaprevir exposure was affected. CONCLUSIONS: The efficacy of the OC may be compromised by the 26% to 33% reduction in EE exposure. Therefore, alternative methods of nonhormonal contraception should be used when hormonal contraceptives are coadministered with telaprevir and for up to 2 weeks following cessation of telaprevir. PMID- 22039292 TI - The radioprotection management of a PET department with a cyclotron and radiopharmacy laboratory, in accordance with Italian legislation. AB - The possibility of setting up a positron emission tomography (PET) facility with a cyclotron and radiopharmaceutical laboratory in situ, at a feasible price and in a very restricted space, has led to a steady increase both in the use of the PET technique in diagnostic clinical routine imaging and in the number of cyclotrons for drug production. Owing to the progress made in the PET procedures, it is now possible to have not only a highly innovative system of diagnostic examination, with a remarkable improvement in the diagnostic quality and patient care, but also a considerable increase in the number of daily examinations. In this paper, the authors show how the acquired know-how, with respect to radioprotection, has applied to the planning, running and management of the PET/CT unit, installed in the Imaging Diagnostic Department of the Policlinico Tor Vergata (PTV), at Tor Vergata University, Rome. PMID- 22039293 TI - Release criteria for patients having undergone radionuclide therapy and criteria for their crossing the state border of the Russian Federation. AB - By means of a conservative dosimetry model, the values of operational radiological criteria for patients released from hospital--residual activity in a body and dose rate near the patient's body--are substantiated based on the effective dose limit of 5 mSv for persons helping the patient or living with him and 1 mSv for other adults and children. Two sets of operative criteria for radionuclides (125)I, (131)I, (153)Sm and (188)Re used in Russia for radionuclide therapy were derived. Release criteria for (125)I well differ from such values in other countries because in this work absorption of (125)I low-energy photon radiation in the patient was taken into account. When a patient having undergone radionuclide therapy crosses the frontier of Russia, high-sensitivity devices for radiation control at the custom can detect the patient. A simplified radiological assessment of the patient was suggested aimed at provision of radiation safety for patient companions in transport. PMID- 22039294 TI - Effective education in radiation safety for nurses. AB - In order to establish an efficient training program of radiation safety for nurses, studies have been carried out on the basis of questionnaires. Collaboration of nurses, who are usually standing closest to the patient, is necessary in order to offer safe radiological diagnostics/treatment. The authors distributed the questionnaire to 134 nurses in five polyclinic hospitals in Japan. Important questions were: fear of radiation exposure, knowledge on the radiation treatment, understanding the impact on pregnancy, and so on. Most of the nurses feel themselves uneasy against exposure to radiation. They do not have enough knowledge of radiological treatment. They do not know exactly what is the impact of the radiation on pregnant women. Such tendency is more pronounced, when nurses spend less time working in the radiological department. Nurses play important roles in radiological diagnostics/treatment. Therefore, a well developed education system for radiation safety is essential. The training for the radiation safety in medicine should be done in the context of general safety in medicine. Education programs in undergraduate school and at the working place should be coordinated efficiently in order to ensure that both nurses and patients are informed about the meaning of radiation safety. PMID- 22039295 TI - Infant homicide in the USA between 1940 and 2005. PMID- 22039296 TI - Use of natural variation reveals core genes in the transcriptome of iron deficient Arabidopsis thaliana roots. AB - Iron (Fe) is an essential mineral micronutrient for plants and animals. Plants respond to Fe deficiency by increasing root uptake capacity. Identification of gene networks for Fe uptake and homeostasis could result in improved crop growth and nutritional value. Previous studies have used microarrays to identify a large number of genes regulated by Fe deficiency in roots of three Arabidopsis ecotypes. However, a large proportion of these genes may be involved in secondary or genotype-influenced responses rather than in a universal role in Fe uptake or homeostasis. Here we show that a small percentage of the Fe deficiency transcriptome of two contrasting ecotypes, Kas-1 and Tsu-1, was shared with other ecotypes. Kas-1 and Tsu-1 had different timing and magnitude of ferric reductase activity upon Fe withdrawal, and different categories of overrepresented Fe regulated genes. To gain insights into universal responses of Arabidopsis to Fe deficiency, the Kas-1 and Tsu-1 transcriptomes were compared with those of Col-0, Ler, and C24. In early Fe deficiency (24-48 h), no Fe-downregulated genes and only 10 upregulated genes were found in all ecotypes, and only 20 Fe downregulated and 58 upregulated genes were found in at least three of the five ecotypes. Supernode gene networks were constructed to visualize conserved Fe homeostasis responses. Contrasting gene expression highlighted different responses to Fe deficiency between ecotypes. This study demonstrates the use of natural variation to identify central Fe-deficiency-regulated genes in plants, and identified genes with potential new roles in signalling during Fe deficiency. PMID- 22039297 TI - Cavitation induced by a surfactant leads to a transient release of water stress and subsequent 'run away' embolism in Scots pine (Pinus sylvestris) seedlings. AB - Cavitation decreases the hydraulic conductance of the xylem and has, therefore, detrimental effects on plant water balance. However, cavitation is also hypothesized to relieve water stress temporarily by releasing water from embolizing conduits to the transpiration stream. Stomatal closure in response to decreasing water potentials in order to avoid excessive cavitation has been well documented in numerous previous studies. However, it has remained unclear whether the stomata sense cavitation events themselves or whether they act in response to a decrease in leaf water potential to a level at which cavitation is initiated. The effects of massive cavitation on leaf water potential, transpiration, and stomatal behaviour were studied by feeding a surfactant into the transpiration stream of Scots pine (Pinus sylvestris) seedlings. The stomatal response to cavitation in connection with the capacitive effect was also studied. A major transient increase in leaf water potential was found due to cavitation in the seedlings. As cavitation was induced by lowering the surface tension, the two mechanisms could be uncoupled, as the usual relation between xylem water potential and the onset of cavitation did not hold. Our results indicate that the seedlings responded more to leaf water potential and less to cavitation itself, as stomatal closure was insufficient to prevent the seedlings from being driven to 'run-away' cavitation in a manner of hours. PMID- 22039298 TI - Homeologous gene expression in response to growing temperature in a recent Allopolyploid (Coffea arabica L.). AB - Allopolyploidy is considered as a major factor contributing to speciation, diversification, and plant ecological adaptation. In particular, the expression of duplicate genes (homeologs) can be altered leading to functional plasticity and to phenotypic novelty. This study investigated the influence of growing temperatures on homeologous gene expression in Coffea arabica L., a recent allopolyploid involving 2 closely related diploid parental species. The relative expression of homeologs of 13 genes all located in the same genomic region was analyzed using an SNP ratio quantification method based on dideoxy-terminated sequences of cDNA amplicons. The relative expression of homeologous genes varied depending on the gene, the organ, and the growing condition. Nevertheless, expression of both homeologs was always detected (i.e., no silencing). Although the growing conditions were suitable for one or other of the parental species, neither subgenome appeared preferentially expressed. Furthermore, relative homeologous expression showed moderate variations across organs and conditions and appeared uncorrelated between adjacent genes. These results indicate the absence of signs of subfunctionalization suggesting C. arabica has not undergone noticeable diploidization. Furthermore, these results suggest that the expression of homeologous genes in C. arabica is regulated by a shared trans-regulation mechanism acting similarly on the 2 subgenomes and that the observed biases in the relative homeolog expression may result from cis fine-scale factors. PMID- 22039299 TI - T cell factor 1 regulates thymocyte survival via a RORgammat-dependent pathway. AB - Survival of CD4(+)CD8(+) double-positive (DP) thymocytes plays a critical role in shaping the peripheral T cell repertoire. However, the mechanisms responsible for the regulation of DP thymocyte lifespan remain poorly understood. In this work, we demonstrate that T cell factor (TCF)-1 regulates DP thymocyte survival by upregulating RORgammat. Microarray analysis revealed that RORgammat was significantly downregulated in TCF-1(-/-) thymocytes that underwent accelerated apoptosis, whereas RORgammat was greatly upregulated in thymocytes that had enhanced survival due to transgenic expression of a stabilized beta-catenin (beta cat(Tg)), a TCF-1 activator. Both TCF-1(-/-) and RORgammat(-/-) DP thymocytes underwent similar accelerated apoptosis. Forced expression of RORgammat successfully rescued TCF-1(-/-) DP thymocytes from apoptosis, whereas ectopically expressed TCF-1 was not able to rescue the defective T cell development because of the lack of RORgammat-supported survival. Furthermore, activation of TCF-1 by stabilized beta-catenin was able to enhance DP thymocyte survival only in the presence of RORgammat, indicating that RORgammat acts downstream of TCF-1 in the regulation of DP thymocyte survival. Moreover, beta-catenin/TCF-1 directly interacted with the RORgammat promoter region and stimulated its activity. Therefore, our data demonstrated that TCF-1 enhances DP thymocyte survival through transcriptional upregulation of RORgammat, which we previously showed is an essential prosurvival molecule for DP thymocytes. PMID- 22039300 TI - A p53 defect sensitizes various stages of B cell development to lymphomagenesis in mice carrying an IgH 3' regulatory region-driven c-myc transgene. AB - Although c-myc is classically described as the driving oncogene in Burkitt's lymphoma (BL), deregulation and mutations of c-myc have been reported in multiple solid tumors and in other mature B cell malignancies such as mantle cell lymphoma (MCL), myeloma, and plasma cell lymphoma (PCL). After translocation into the IgH locus, c-myc is constitutively expressed under the control of active IgH enhancers. Those located in the IgH 3' regulatory region (3'RR) are master control elements of class switch recombination and of the transcriptional burst associated with plasma cell differentiation. c-myc-3'RR mice are prone to lymphomas with rather homogeneous, most often BL-like, phenotypes with incomplete penetrance (75% tumor incidence) and long latencies (10-12 mo). To reproduce c myc-induced mature B cell lymphomagenesis in the context of an additional defect often observed in human lymphomas, we intercrossed c-myc-3'RR with p53(+/-) mice. Double transgenic c-myc-3'RR/p53(+/-) mice developed lymphoma with short latency (2-4 mo) and full penetrance (100% tumor incidence). The spectrum of B lymphomas occurring in c-myc-3'RR/p53(+/-) mice was widened, including nonactivated (CD43( )) BL, activated (CD43(+)) BL, MCL-like lymphoma, and PCL, thus showing that 3'RR mediated deregulation of c-myc can promote various types of B lymphoproliferation in cells that first acquired a p53 defect. c-myc/p53(+/-) mice closely reproduce many features of BL, MCL, and PCL and provide a novel and efficient model to dissect the molecular events leading to c-myc-induced lymphomagenesis and an important tool to test potential therapeutic agents on malignant B cells featuring various maturation stages. PMID- 22039301 TI - Glycogen synthase kinase-3beta is a prosurvival signal for the maintenance of human mast cell homeostasis. AB - Homeostasis of mature tissue-resident mast cells is dependent on the relative activation of pro- and antiapoptotic regulators. In this study, we investigated the role of glycogen synthase kinase 3beta (GSK3beta) in the survival of neoplastic and nonneoplastic human mast cells. GSK3beta was observed to be phosphorylated at the Y(216) activating residue under resting conditions in both the neoplastic HMC1.2 cell line and in peripheral blood-derived primary human mast cells (HuMCs), suggesting constitutive activation of GSK3beta in these cells. Lentiviral-transduced short hairpin RNA knockdown of GSK3beta in both the HMC1.2 cells and HuMCs resulted in a significant reduction in cell survival as determined with the MTT assay. The decrease in stem cell factor (SCF)-mediated survival in the GSK3beta knockdown HuMCs was reflected by enhancement of SCF withdrawal-induced apoptosis, as determined by Annexin V staining and caspase cleavage, and this was associated with a pronounced reduction in SCF-mediated phosphorylation of Src homology 2 domain-containing phosphatase 2 and ERK1/2 and reduced expression of the antiapoptotic proteins Bcl-xl and Bcl-2. These data show that GSK3beta is an essential antiapoptotic factor in both neopastic and nontransformed primary human mast cells through the regulation of SCF-mediated Src homology 2 domain-containing phosphatase 2 and ERK activation. Our data suggest that targeting of GSK3beta with small m.w. inhibitors such as CHIR 99021 may thus provide a mechanism for limiting mast cell survival and subsequently decreasing the intensity of the allergic inflammatory response. PMID- 22039302 TI - Adenosinergic regulation of the expansion and immunosuppressive activity of CD11b+Gr1+ cells. AB - Extracellular adenosine and purine nucleotides are elevated in many pathological situations associated with the expansion of CD11b(+)Gr1(+) myeloid-derived suppressor cells (MDSCs). Therefore, we tested whether adenosinergic pathways play a role in MDSC expansion and functions. We found that A(2B) adenosine receptors on hematopoietic cells play an important role in accumulation of intratumoral CD11b(+)Gr1(high) cells in a mouse Lewis lung carcinoma model in vivo and demonstrated that these receptors promote preferential expansion of the granulocytic CD11b(+)Gr1(high) subset of MDSCs in vitro. Flow cytometry analysis of MDSCs generated from mouse hematopoietic progenitor cells revealed that the CD11b(+)Gr-1(high) subset had the highest levels of CD73 (ecto-5'-nucleotidase) expression (Deltamean fluorescence intensity [MFI] of 118.5 +/- 16.8), followed by CD11b(+)Gr-1(int) (DeltaMFI of 57.9 +/- 6.8) and CD11b(+)Gr-1(-/low) (DeltaMFI of 12.4 +/- 1.0) subsets. Even lower levels of CD73 expression were found on Lewis lung carcinoma tumor cells (DeltaMFI of 3.2 +/- 0.2). The high levels of CD73 expression in granulocytic CD11b(+)Gr-1(high) cells correlated with high levels of ecto-5'-nucleotidase enzymatic activity. We further demonstrated that the ability of granulocytic MDSCs to suppress CD3/CD28-induced T cell proliferation was significantly facilitated in the presence of the ecto-5' nucleotidase substrate 5'-AMP. We propose that generation of adenosine by CD73 expressed at high levels on granulocytic MDSCs may promote their expansion and facilitate their immunosuppressive activity. PMID- 22039303 TI - Cutting edge: Nicastrin and related components of gamma-secretase generate a peptide epitope facilitating immune recognition of intracellular mycobacteria, through MHC class II-dependent priming of T cells. AB - Bacillus Calmette-Guerin (BCG), the antituberculosis vaccine, localizes within immature phagosomes of macrophages and dendritic cells (APCs), and avoids lysosomal degradation. BCG-derived antigenic peptides are thus inefficiently processed by APCs, and we investigated alternate mechanisms of Ag processing. Proteomics identified that BCG phagosomes are enriched for nicastrin, APH, and presenilin components of gamma-secretase, a multimeric protease. Using an in vitro Ag presentation assay and BCG-infected APCs, we found gamma-secretase components to cleave BCG-derived Ag85B to produce a peptide epitope, which, in turn, primed IL-2 release from Ag85B-specific T cell hybridoma. siRNA knockdown or chemical inhibition of gamma-secretase components using L685458 decreased the ability of BCG or Mycobacterium tuberculosis-infected APCs to present Ag85B. In addition, L685485 inhibition of gamma-secretase led to a decreased ability of BCG dendritic cells to immunize mice and induce Ag85B-specific CD4 T cells in vivo. Because BCG and M. tuberculosis sequester within APCs preventing immune recognition, gamma-secretase components appear to fortuitously process the immunodominant Ag85B, facilitating immune recognition. PMID- 22039305 TI - Affinity thresholds for naive CD8+ CTL activation by peptides and engineered influenza A viruses. AB - High-avidity interactions between TCRs and peptide + class I MHC (pMHCI) epitopes drive CTL activation and expansion. Intriguing questions remain concerning the constraints determining optimal TCR/pMHCI binding. The present analysis uses the TCR transgenic OT-I model to assess how varying profiles of TCR/pMHCI avidity influence naive CTL proliferation and the acquisition of effector function following exposure to the cognate H-2K(b)/OVA(257-264) (SIINFEKL) epitope and to mutants provided as peptide or in engineered influenza A viruses. Stimulating naive OT-I CD8(+) T cells in vitro with SIINFEKL induced full CTL proliferation and differentiation that was largely independent of any need for costimulation. By contrast, in vitro activation with the low-affinity EIINFEKL or SIIGFEKL ligands depended on the provision of IL-2 and other costimulatory signals. Importantly, although they did generate potent endogenous responses, infection of mice with influenza A viruses expressing these same OVA(257) variants failed to induce the activation of adoptively transferred naive OT-I CTLps, an effect that was only partially overcome by priming with a lipopeptide vaccine. Subsequent structural and biophysical analysis of H2-K(b)OVA(257), H2-K(b)E1, and H2-K(b)G4 established that these variations introduce small changes at the pMHCI interface and decrease epitope stability in ways that would likely impact cell surface presentation and recognition. Overall, it seems that there is an activation threshold for naive CTLps, that minimal alterations in peptide sequence can have profound effects, and that the antigenic requirements for the in vitro and in vivo induction of CTL proliferation and effector function differ substantially. PMID- 22039304 TI - c-Myb and GATA-3 cooperatively regulate IL-13 expression via conserved GATA-3 response element and recruit mixed lineage leukemia (MLL) for histone modification of the IL-13 locus. AB - The c-Myb and GATA-3 transcription factors play important roles in T cell development. We recently reported that c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression and ultimately Th2 cell development in human peripheral blood T cells. However, c-Myb roles for Th2 cytokine expression were not demonstrated. In this article, we report that c-Myb and GATA-3 cooperatively play an essential role in IL-13 expression though direct binding to a conserved GATA-3 response element (CGRE), an enhancer for IL-13 expression. c-Myb and GATA-3 were shown to activate the CGRE-IL-13 promoter by ~160-fold, and mutation of the canonical Myb binding site completely abrogated CGRE enhancer activity. In contrast, mutation of the GATA binding site partially decreased CGRE enhancer activity. GATA-3 did not bind to CGRE when c-myb expression was silenced. c-Myb, GATA-3, Menin, and mixed lineage leukemia (MLL) bound to CGRE in human primary CD4(+) effector/memory cells. Moreover, c-myb silencing significantly decreased both methylation of histone H3K4 and acetylation of histone H3K9 at the IL-13 locus in CD4(+) effector/memory cells. Therefore, in addition to the strong enhancer effect for the transcription of IL 13, the c-Myb/GATA-3 complex recruits MLL to the CGRE for histone modification of the IL-13 locus during the differentiation of memory Th2 cells. PMID- 22039306 TI - alpha9beta1 integrin-mediated signaling serves as an intrinsic regulator of pathogenic Th17 cell generation. AB - The interaction between matricellular proteins such as tenascin-C (TN-C) and osteopontin (OPN) and integrins has been implicated in the pathology of rheumatoid arthritis in which Th17 cells are recognized as primary pathogenic cells. The differentiation of Th17 cells is tightly regulated by cytokines derived from APCs, receiving various signals including TLR stimuli. In this study, we used a collagen-induced arthritis model and found that increased numbers of alpha(9) integrin-positive conventional dendritic cells and macrophage were detectable in the draining lymph node (dLN) shortly following first immunization, and these cells produced both TN-C and OPN, ligands for alpha(9) integrin. alpha(9) integrin-mediated signaling, induced by TN-C and OPN, promoted the production of Th17-related cytokines by conventional dendritic cells and macrophages in synergy with TLR2 and 4 signaling. This led to the Th17 cell differentiation and arthritis development. Moreover, Th17 cells generated under blocking of alpha(9) integrin-mediated signaling showed low level of CCR6 expression and impaired migration ability toward CCL20. Thus, we have identified alpha(9) integrin-mediated signaling by TN-C and OPN as a novel intrinsic regulator of pathogenic Th17 cell generation that contributes to the development of rheumatoid arthritis. PMID- 22039307 TI - EphB receptors trigger Akt activation and suppress Fas receptor-induced apoptosis in malignant T lymphocytes. AB - Treatment of hematopoietic malignancies often requires allogeneic bone marrow transplantation, and the subsequent graft-versus-leukemia response is crucial for the elimination of malignant cells. Cytotoxic T lymphocytes and NK cells responsible for the immunoelimination express Fas ligand and strongly rely on the induction of Fas receptor-mediated apoptosis for their action. Although cancer cells are removed successfully by graft-versus-leukemia reactions in myeloid malignancies, their efficiency is low in T cell leukemias. This may be partially because of the ability of malignant T cells to escape apoptosis. Our work shows that Eph family receptor EphB3 is consistently expressed by malignant T lymphocytes, most frequently in combination with EphB6, and that stimulation with their common ligands, ephrin-B1 and ephrin-B2, strongly suppresses Fas-induced apoptosis in these cells. This effect is associated with Akt activation and with the inhibition of the Fas receptor-initiated caspase proteolytic cascade. Akt proved to be crucial for the prosurvival response, because inhibition of Akt, but not of other molecules central to T cell biology, including Src kinases, MEK1 and MEK2, blocked the antiapoptotic effect. Overall, this demonstrates a new role for EphB receptors in the protection of malignant T cells from Fas-induced apoptosis through Akt engagement and prevention of caspase activation. Because Fas triggered apoptosis is actively involved in the graft-versus-leukemia response and cytotoxic T cells express ephrin-Bs, our observations suggest that EphB receptors are likely to support immunoevasivenes of T cell malignancies and may represent promising targets for therapies, aiming to enhance immunoelimination of cancerous T cells. PMID- 22039308 TI - LED-Based Optical Device for Chronic In Vivo Cerebral Blood Volume Measurement. AB - We demonstrate a reflectivity-based cerebral blood volume sensor comprised of surface-mount light-emitting diodes on a flexible substrate with integrated photodetectors in a form factor suitable for direct brain contact and chronic implantation. This reflectivity monitor is able to measure blood flow through the change of the surface reflectivity and, through this mechanism, detect the cerebral-blood-volume changes associated with epileptic seizures with a signal-to noise (SNR) response of 42 dB. The device is tested in an in vivo model confirming its compatibility and sensitivity. The data taken demonstrate that placing the sensor into direct brain contact improves the SNR by more than four orders of magnitude over current noncontact technologies. PMID- 22039309 TI - Intergenerational Coresidence and Family Transitions in the United States, 1850 - 1880. AB - This study uses a new source of linked census data (N = 6,734) to test theories proposed to explain the high intergenerational coresidence in 19th-century America. Was it a system of support for dependent elderly, or did it reflect intergenerational interdependence? I focus on transitions from middle age to old age, and I assess key predictors of family transitions, including widowhood, retirement, disability, migration, and wealth. The results show that adverse events precipitated changes in the headship of intergenerational families but did not increase the likelihood of residing in an intergenerational family. The findings suggest that 19th-century intergenerational coresidence was not principally a means of old-age support; more often, probably, there was a reciprocal relationship between generations. PMID- 22039310 TI - Nickel-Catalyzed Cycloisomerization of Enynes: Catalyst Generation via C-H Activation of Carbene Ligands. AB - The combination of Ni(0) and an N-heterocyclic carbene act as a precatalyst for the cycloisomerization of enynes to afford 1,3-dienes. During the course of the reaction, a nickel hydride is formed from oxidative addition of the ortho C-H on the carbene ligand. Deuteriumn labeling studies are presented. PMID- 22039311 TI - Thermodynamic properties of liquid Au-Cu-Sn alloys determined from electromotive force measurements. AB - The thermodynamic properties of the ternary Au-Cu-Sn system were determined with the electromotive force (EMF) method using a liquid electrolyte. Three different cross-sections with constant Au:Cu ratios of 3:1, 1:1, and 1:3 were applied to measure the thermodynamic properties of the ternary system in the temperature range between the liquidus temperature of the alloys and 1023 K. The partial free energies of Sn in liquid Au-Cu-Sn alloys were obtained from EMF data. The integral Gibbs free energy and the integral enthalpy at 900 K were calculated by Gibbs-Duhem integration. The ternary interaction parameters were evaluated using the Redlich-Kister-Muggianu polynomial. PMID- 22039312 TI - Patterns and Predictors of Early Care and Education for Children in Foster Care. PMID- 22039313 TI - Cross-Location Analysis of the Impact of Household Socioeconomic Status on Participation in Urban and Peri-Urban Agriculture in West Africa. AB - This study explores the relation between household socioeconomic status (SES) and participation in urban and periurban agriculture (UPA) in three West African cities. We used a structured questionnaire to survey 700 randomly selected households: 250 in Kano, Nigeria, 250 in Bobo Dioulasso, Burkina Faso, and 200 in Sikasso, Mali. Multiple correspondence analysis was applied on household asset variables to create an index of assets which was used as a proxy for household SES. The results showed no significant differences in households' rate of participation in UPA across socioeconomic groups. Participation in UPA was rather significantly (P < 0.001) and positively related to household size. Interestingly, the analysis revealed that field crop cultivation and gardening were more common among households in the low and medium SES groups while those in the high SES group were more likely to keep livestock. PMID- 22039315 TI - Incentive-Related Human Resource Practices for Substance Use Disorder Counselors: Salaries, Benefits, and Training. AB - Understanding factors associated with incentive-related human resource practices for substance use disorder counselors can help promote a stable workforce in this occupation. We examined three counselor incentives-salaries, benefits, training and the link with organizational, counselor, and patient characteristics. Data were collected in 2007/08 via face-to-face interviews with 345 administrators/clinical directors in private treatment centers. Centers paid counselors an average of $38,800 annually and provided a mean of 2.83 benefits and 1.61 training (0-4 scales). Characteristics differed based on the incentive. Centers' managements need to be aware of different incentives that can help attract and retain counselors. PMID- 22039316 TI - An Evaluation of the Relation Between Distress Tolerance and Posttraumatic Stress within a Trauma-Exposed Sample. AB - The present investigation examined the incremental associations between distress tolerance, or the perceived capacity to tolerate emotional distress, and global posttraumatic stress symptom severity as well as symptom cluster severity, beyond the variance accounted for by number of trauma exposure types and negative affectivity. The sample consisted of 140 adults (72 women; M(age)=25.9, SD=11.1) who endorsed exposure to traumatic life events, as defined by posttraumatic stress disorder diagnostic criterion A (American Psychiatric Association 2000). Participants did not meet diagnostic criteria for current axis I psychopathology. Distress tolerance demonstrated significant incremental associations with global posttraumatic stress symptom severity (p<.01) as well as re-experiencing (p<.05), avoidance (p=.05), and hyperarousal (p<.001) symptom cluster severity. Given the cross-sectional study design, causation cannot be inferred. Theoretical implications and future directions for better understanding associations between distress tolerance and posttraumatic stress are discussed. PMID- 22039317 TI - II. Electrodeposition/removal of nickel in a spouted electrochemical reactor. AB - An investigation is presented of nickel electrodeposition from acidic solutions in a cylindrical spouted electrochemical reactor. The effects of solution pH, temperature, and applied current on nickel removal/recovery rate, current efficiency, and corrosion rate of deposited nickel on the cathodic particles were explored under galvanostatic operation. Nitrogen sparging was used to decrease the dissolved oxygen concentration in the electrolyte in order to reduce the nickel corrosion rate, thereby increasing the nickel electrowinning rate and current efficiency. A numerical model of electrodeposition, including corrosion and mass transfer in the particulate cathode moving bed, is presented that describes the behavior of the experimental net nickel electrodeposition data quite well. PMID- 22039318 TI - Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis. AB - Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease. A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis. Due to the obesity epidemic, fatty liver is now a significant problem in clinical practice. Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes. An association between hepatitis C virus (HCV) infection, steatosis and the onset of insulin resistance has been reported. Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections. Moreover, hyperinsulinemia has a deleterious effect on the management of chronic HCV. Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin. The underlying mechanisms of this complex interaction are not fully understood. A direct cytopathic effect of HCV has been suggested. The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides), lipid metabolism, the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated. PMID- 22039319 TI - Digestive manifestations of parathyroid disorders. AB - The parathyroid glands are the main regulator of plasma calcium and have a direct influence on the digestive tract. Parathyroid disturbances often result in unknown long-standing symptoms. The main manifestation of hypoparathyroidism is steatorrhea due to a deficit in exocrine pancreas secretion. The association with celiac sprue may contribute to malabsorption. Hyperparathyroidism causes smooth muscle atony, with upper and lower gastrointestinal symptoms such as nausea, heartburn and constipation. Hyperparathyroidism and peptic ulcer were strongly linked before the advent of proton pump inhibitors. Nowadays, this association remains likely only in the particular context of multiple endocrine neoplasia type 1/Zollinger-Ellison syndrome. In contrast to chronic pancreatitis, acute pancreatitis due to primary hyperparathyroidism is one of the most studied topics. The causative effect of high calcium level is confirmed and the distinction from secondary hyperparathyroidism is mandatory. The digestive manifestations of parathyroid malfunction are often overlooked and serum calcium level must be included in the routine workup for abdominal symptoms. PMID- 22039320 TI - Current treatment for colorectal liver metastases. AB - Surgical resection offers the best opportunity for survival in patients with colorectal cancer metastatic to the liver, with five-year survival rates up to 58% in selected cases. However, only a minority are resectable at the time of diagnosis. Continuous research in this field aims at increasing the percentage of patients eligible for resection, refining the indications and contraindications for surgery, and improving overall survival. The use of surgical innovations, such as staged resection, portal vein embolization, and repeat resection has allowed higher resection rates in patients with bilobar disease. The use of neoadjuvant chemotherapy allows up to 38% of patients previously considered unresectable to be significantly downstaged and eligible for hepatic resection. Ablative techniques have gained wide acceptance as an adjunct to surgical resection and in the management of patients who are not surgical candidates. Current management of colorectal liver metastases requires a multidisciplinary approach, which should be individualized in each case. PMID- 22039321 TI - Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis. AB - AIM: To determine the effect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfon-ic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a non-selective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL 1beta and tumor necrosis factor (TNF)-alpha were assessed. The effects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro 4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL-1beta and TNF-alpha levels. These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NO(x) content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1beta and TNF-alpha mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASA-induced improvement of colonic healing and the accompanying increase in the CBF. These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals. CONCLUSION: NO-releasing ASA, in contrast to ASA, COX-1 inhibitors, and SC-560, accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP. PMID- 22039322 TI - Inhibition of high-mobility group box 1 expression by siRNA in rat hepatic stellate cells. AB - AIM: To explore the role of high-mobility group box 1 (HMGB1) protein during liver fibrogenesis and investigate the functional effects of HMGB1 gene silencing in hepatic stellate cells (HSCs) using siRNA. METHODS: Hepatic fibrosis in rats was induced throu-gh serial subcutaneous injections of dimethylnitrosamine, and expression of HMGB1 was detected by immunohistochemistry. HMGB1 siRNAs were developed and transiently transfected into HSC-T6 cells using Lipofectamine 2000. HMGB1 expression was evaluated by real-time polymerase chain reaction (PCR) and Western blotting analysis. Expression of alpha-smooth muscle actin (alpha-SMA) and collagen types I and III was evaluated by real-time PCR. Cell proliferation and the cell cycle were determined using the methyl thiazolyl tetrazolium method. Finally, collagen content in HSC supernatant was evaluated by an enzyme-linked immunosorbent assay. RESULTS: The results showed that HMGB1 was upregulated during liver fibrosis and that its expression was closely correlated with the deposition of collagen. siRNA molecules were successfully transfected into HSCs and induced inhibition of HMGB1 expression in a time-dependent manner. Moreover, HMGB1 siRNA treatment inhibited synthesis of alpha-SMA and collagen types I and III in transfected HSCs. CONCLUSION: This study suggests a significant fun ctional role for HMGB1 in the development of liver fibrosis. It also demonstrates that downregulation of HMGB1 expression might be a potential strategy to treat liver fibrosis. PMID- 22039323 TI - Antioxidative potential of a combined therapy of anti TNFalpha and Zn acetate in experimental colitis. AB - AIM: To evaluate whether combination therapy with anti-tumour necrosis factor alpha (TNFalpha) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis. METHODS: Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d. The experimental mice were then randomised into the following subgroups: standard diet + DSS treated (induced colitis group); standard diet + DSS + subcutaneous 25 MUg anti-TNFalpha treated group; Zn acetate treated group + DSS + subcutaneous 25 MUg anti-TNFalpha; standard diet + DSS + subcutaneous 6.25 MUg anti-TNFalpha treated group and Zn acetate treated group + DSS + subcutaneous 6.25 MUg anti-TNFalpha. Each group of mice was matched with a similar group of sham control animals. Macroscopic and histological features were scored blindly. Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage. RESULTS: DSS produced submucosal erosions, ulcers, inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFalpha alone or combined with zinc. The effect was more pronounced in the latter group (vs Zn diet, P < 0.02). Myeloperoxidase activity (vs controls, P < 0.02) and DNA adducts, greatly elevated in the DSS fed colitis group (vs controls, P < 0.05), were significantly reduced in the treated groups, with a more remarkable effect in the group receiving combined therapy (vs standard diet, P < 0.04). CONCLUSION: DSS induces colonic inflammation which is modulated by the administration of anti-TNFalpha. Combining anti-TNFalpha with Zn acetate offers marginal benefit in colitis severity. PMID- 22039324 TI - Helicobacter species and gut bacterial DNA in Meckel's diverticulum and the appendix. AB - AIM: To analyse the possible association of various Helicobacter species and certain common gut bacteria in patients with Meckel's diverticulum and appendicitis. METHODS: A nested-polymerase chain reaction (PCR), specific to 16S rRNA of the Helicobacter genus, was performed on paraffin embedded samples, 50 with acute appendicitis, 50 normal appendixes, and 33 Meckel's diverticulum with gastric heterotopia and/or ulcer. Helicobacter genus positive samples were sequenced for species identification. All samples were also analysed for certain gut bacteria by PCR. RESULTS: Helicobacter pullorum DNA was found in one out of 33 cases and Enterobacteria in two cases of Meckel's diverticulum. Helicobacter pylori (H. pylori) was found in three, Enterobacter in 18, and Bacteroides in 19 out of 100 appendix samples by PCR. Enterococcus was not found in any MD or appendix samples. All H. pylori positive cases were from normal appendixes. CONCLUSION: Helicobacter is not an etiological agent in the pathogenesis of symptomatic Meckel's diverticulum or in acute appendicitis. PMID- 22039325 TI - Epinephrine plus argon plasma or heater probe coagulation in ulcer bleeding. AB - AIM: To compare the effectiveness of argon plasma coagulation (APC) and heater probe coagulation (HPC) in non-variceal upper gastrointestinal bleeding. METHODS: Eighty-five (18 female, 67 male) patients admitted for acute gastrointestinal bleeding due to gastric or duodenal ulcer were included in the study. Upper endoscopy was performed and HPC or APC were chosen randomly to stop the bleeding. Initial hemostasis and rebleeding rates were primary and secondary end-points of the study. RESULTS: Initial hemostasis was achieved in 97.7% (42/43) and 81% (36/42) of the APC and HPC groups, respectively (P < 0.05). Rebleeding rates were 2.4% (1/42) and 8.3% (3/36) in the APC and HPC groups, respectively, at 4 wk (P > 0.05). CONCLUSION: APC is an effective hemostatic method in bleeding peptic ulcers. Larger multicenter trials are necessary to confirm these results. PMID- 22039326 TI - Role of cyclooxygenase-2 gene polymorphisms in pancreatic carcinogenesis. AB - AIM: To evaluate the clinical significance of -765G/C and -1195G/A cyclooxygenase 2 (COX-2) gene polymorphisms in patients with pancreatic cancer (PC). METHODS: The study included 201 patients: 85 with PC and 116 healthy controls. -765G/C and -1195G/A COX-2 gene polymorphisms were studied in DNA isolated from blood samples. The associations of the analyzed genotypes and clinical data at diagnosis were evaluated. RESULTS: We found an increased frequency of the homozygous -1195AA COX-2 genotype in patients with PC (53.7%) compared with the control group (21%) (P < 0.01). In contrast, the distribution of genotype and allele frequencies of the -765G/C COX-2 polymorphism in the PC patients were not different from those in control groups. A correlation between presence of homozygous -1195AA COX-2 genotype and tumor size > 3 cm was observed (P < 0.05). Analyzed polymorphisms were unrelated to the patients' sex and age, nor to the presence of regional or distant metastases. CONCLUSION: These preliminary results indicate that the -1195G/A COX-2 polymorphism may play an important role in PC prognosis and carcinogenesis. PMID- 22039327 TI - Does the bile duct angulation affect recurrence of choledocholithiasis? AB - AIM: To investigate whether bile duct angulation and T-tube choledochostomy influence the recurrence of choledocholithiasis. METHODS: We conducted a retrospective study inclu-ding 259 patients who underwent endoscopic sphincterotomy and cholecystectomy for choledocholithiasis between 2000 and 2007. The imaginary line was drawn along the center of the bile duct and each internal angle was measured at the two angulation sites of the bile duct respectively. The values of both angles were added together. We then tested our hypothesis by examining whether T-tube choledochostomy was performed and stone recurrence occurred by reviewing each subject's medical records. RESULTS: The overall recurrence rate was 9.3% (24 of 259 patients). The mean value of sums of angles in the recurrence group was 268.3 degrees +/- 29.6 degrees , while that in the non-recurrence group was 314.8 degrees +/- 19.9 degrees (P < 0.05). Recurrence rate of the T-tube group was 15.9% (17 of 107), while that of the non T-tube group was 4.6% (7 of 152) (P < 0.05). Mean value of sums of angles after T-tube drainage was 262.5 degrees +/- 24.6 degrees and that before T-tube drainage was 298.0 degrees +/- 23.9 degrees in 22 patients (P < 0.05). CONCLUSION: The bile duct angulation and T-tube choledochostomy may be risk factors of recurrence of bile duct stones. PMID- 22039328 TI - Assessment of participant satisfaction with upper gastrointestinal endoscopy in South Korea. AB - AIM: To measure the perceived satisfaction with gastric cancer screening as part of the National Cancer Screening Program (NCSP) in South Korea. METHODS: Data were derived from the participants in a satisfaction survey of the Quality Evaluation of National Cancer Screening in 2009. This is a population-based nationwide telephone survey of participants who were screened by the NCSP between May and October 2009. This study included 4412 participants who provided full sets of data and who had upper endoscopies for the purpose of gastric cancer screening. RESULTS: The negative appraisal percentages for each of the seven questions were as follows: explanation in preparation for the upper endoscopy, 12.3%; explanation about the process and procedure of the upper endoscopy, 13.8%; explanation about any pain or discomfort related to the upper endoscopy, 27.5%; level of pain during the procedure, 30.3%; physical environment, 16.2%; manner of the staff, 11.2%, and privacy protection, 8.8%. CONCLUSION: The critical issues identified by the Pareto analysis include the adequacy of the explanation about any pain or discomfort associated with the upper endoscopy and the level of pain experienced during the procedure. PMID- 22039329 TI - Anti-hepatitis A seroprevalence among chronic viral hepatitis patients in Kelantan, Malaysia. AB - AIM: To determine the seroprevalence of anti-hepatitis A virus (HAV) antibodies in patients with chronic liver disease (CLD) and to justify the need for hepatitis A vaccination. METHODS: Patients (n = 119) were enrolled between July and September 2009. The diagnosis of CLD was based on the presence of viral markers for more than 6 mo. The diagnosis of liver cirrhosis was based on clinical, biochemical and radiological profiles. Patient serum was tested for anti-HAV IgG. RESULTS: The overall anti-HAV seroprevalence was 88.2%. The aetiology of CLD was hepatitis B in 96 patients (80.7%) and hepatitis C in 23 patients (19.3%). Mean age was 44.4 +/- 14 years. Patients were grouped according to age as follows: 24 (20.2%) patients in the 21-30 years age group, 22 (18.5%) in the 31-40 years age group, 31 (26.1%) in the 41-50 years age group, 23 (19.3%) in the 51-60 years age group and 19 (16.0%) patients aged greater than 60 years, with reported seroprevalences of 66.7%, 95.5%, 93.5%, 91.3% and 94.7%, respectively. There was a marked increase of seroprevalence in subjects older than 30 years (P = 0.001). CONCLUSION: Our study demonstrated that patients aged greater than 30 years of age were likely to have natural immunity to hepatitis A. Therefore, hepatitis A vaccination may not be routinely required in this age group. PMID- 22039330 TI - Viral kinetics of enterovirus 71 in human abdomyosarcoma cells. AB - AIM: To characterise the viral kinetics of enterovirus 71 (EV71). METHODS: In this study, human rhabdomyosarcoma (RD) cells were infected with EV71 at different multiplicity of infection (MOI). After infection, the cytopathic effect (CPE) was monitored and recorded using a phase contrast microscope associated with a CCD camera at different time points post viral infection (0, 6, 12, 24 h post infection). Cell growth and viability were measured by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in both EV71 infected and mock infected cells at each time point. EV71 replication kinetics in RD cells was determined by measuring the total intracellular viral RNA with real time reverse-transcription polymerase chain reaction (qRT-PCR). Also, the intracellular and extracellular virion RNA was isolated and quantified at different time points to analyze the viral package and secretion. The expression of viral protein was determined by analyze the levels of viral structure protein VP1 with Western blotting. RESULTS: EV71 infection induced a significant CPE as early as 6 h post infection (p.i.) in both RD cells infected with high ratio of virus (MOI 10) and low ratio of virus (MOI 1). In EV71 infected cells, the cell growth was inhibited and the number of viable cells was rapidly decreased in the later phase of infection. EV71 virions were uncoated immediately after entry. The intracellular viral RNA began to increase at as early as 3 h p.i. and the exponential increase was found between 3 h to 6 h p.i. in both infected groups. For viral structure protein synthesis, results from western-blot showed that intracellular viral protein VP1 could not be detected until 6 h p.i. in the cells infected at either MOI 1 or MOI 10; and reached the peak at 9 h p.i. in the cells infected with EV71 at both MOI 1 and MOI 10. Simultaneously, the viral package and secretion were also actively processed as the virus underwent rapid replication. The viral package kinetics was comparable for both MOI 1 and MOI 10 infected groups. It was observed that at 3 h p.i, the intracellular virions obviously decreased, thereafter, the intracellular virions began to increase and enter into the exponential phase until 12 h p.i. The total amounts of intracellular virons were decreased from 12 to 24 h p.i. Consistent with this result, the increase of virus secretion occurred during 6 to 12 h p.i. CONCLUSION: The viral kinetics of EV71 were established by analyzing viral replication, package and secretion in RD cells. PMID- 22039331 TI - Radiofrequency ablation vs hepatic resection for solitary colorectal liver metastasis: a meta-analysis. AB - AIM: To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection (HR) for solitary colorectal liver metastases (CLM). METHODS: A literature search was performed to identify comparative studies reporting outcomes for both RFA and HR for solitary CLM. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using either the fixed effects model or random effects model. RESULTS: Seven nonrandomized controlled trials studies were included in this analysis. These studies included a total of 847 patients: 273 treated with RFA and 574 treated with HR. The 5 years overall survival rates in the HR group were significantly better than those in the RFA group (OR: 0.41, 95% CI: 0.22-0.90, P = 0.008). RFA had a higher rate of local intrahepatic recurrence compared to HR (OR: 4.89, 95% CI: 1.73-13.87, P = 0.003). No differences were found between the two groups with respect to postoperative morbidity and mortality. CONCLUSION: HR was superior to RFA in the treatment of patients with solitary CLM. However, the findings have to be carefully interpreted due to the lower level of evidence. PMID- 22039332 TI - CD133 and membrane microdomains: old facets for future hypotheses. AB - Understanding all facets of membrane microdomains in normal and cancerous cells within the digestive tract is highly important, not only from a clinical point of view, but also in terms of our basic knowledge of cellular transformation. By studying the normal and cancer stem cell-associated molecule CD133 (prominin-1), novel aspects of the organization and dynamics of polarized epithelial cells have been revealed during the last decade. Its association with particular membrane microdomains is highly relevant in these contexts and might also offer new avenues in diagnosis and/or targeting of cancer stem cells. PMID- 22039333 TI - Hook-up Sexual Experiences and Problem Behaviors Among Adolescents. AB - This study focused on the sexual phenomenon of "hooking-up." A hook-up is defined as a single sexual encounter that may or may not include sexual intercourse with someone who is a stranger, brief acquaintance, or friend. The aim of this study was to document the prevalence of hook-ups in a sample of 1,011 urban, middle and high school students and to examine the relationship between hooking-up and a variety of problem behaviors, including, alcohol, cigarette, illicit drug use, truancy, and school suspensions. The results revealed that 28% of the sample had engaged in at least one hook-up experience, and this percentage increased with age. Hook-ups were correlated moderately with all problem behaviors examined. PMID- 22039334 TI - Cerium oxide and platinum nanoparticles protect cells from oxidant-mediated apoptosis. AB - Catalytic nanoparticles represent a potential clinical approach to replace or correct aberrant enzymatic activities in patients. Several diseases, including many blinding eye diseases, are promoted by excessive oxidant stress due to reactive oxygen species (ROS). Cerium oxide and platinum nanoparticles represent two potentially therapeutic nanoparticles that de-toxify ROS. In the present study we directly compare these two classes of catalytic nanoparticles. Cerium oxide and platinum nanoparticles were found to be 16+/-2.4 nm and 1.9+/-0.2 nm in diameter, respectively. Using surface plasmon enhanced microscopy, we find that these nanoparticles associate with cells. Furthermore, cerium oxide and platinum nanoparticles demonstrated superoxide dismutase catalytic activity, but did not promote hemolytic or cytolytic pathways in living cells. Importantly, both cerium oxide and platinum nanoparticles reduce oxidant-mediated apoptosis in target cells as judged by the activation of caspase 3. The ability to diminish apoptosis may contribute to maintaining healthy tissues. PMID- 22039335 TI - Minimizing Skin Color Differences Does Not Eliminate the Own-Race Recognition Advantage in Infants. AB - An abundance of experience with own-race faces and limited to no experience with other-race faces has been associated with better recognition memory for own-race faces in infants, children, and adults. This study investigated the developmental origins of this other-race effect (ORE) by examining the role of a salient perceptual property of faces-that of skin color. Six- and 9-month-olds' recognition memory for own- and other-race faces was examined using infant controlled habituation and visual-paired comparison at test. Infants were shown own- or other-race faces in color or with skin color cues minimized in grayscale images. Results for the color stimuli replicated previous findings that infants show an ORE in face recognition memory. Results for the grayscale stimuli showed that even when a salient perceptual cue to race, such as skin color information, is minimized, 6- to 9-month-olds, nonetheless, show an ORE in their face recognition memory. Infants' use of shape-based and configural cues for face recognition is discussed. PMID- 22039336 TI - Auditory Stream Segregation Improves Infants' Selective Attention to Target Tones Amid Distractors. AB - The present study examined the role of auditory stream segregation in the selective attention to target tones in infancy. Using a task adapted from Bregman and Rudnicky's (1975) study and implemented in a conditioned head-turn procedure, infant and adult listeners had to discriminate the temporal order of 2200 and 2400 Hz target tones presented alone, preceded and followed by 1460 Hz flanker tones, and presented within a series of 1460 Hz captor tones meant to release the target tones from the effects of the flankers by capturing the flankers into a separate stream. Infants showed the same pattern of discrimination across conditions as adults: discrimination of target tones in the target-alone condition, a decrease in performance when flanker tones were introduced, and a return to target-alone level in the captor condition. These results suggest that infants' perceptual organization of tones is similar to that of adults, and that their ability to selectively attend to target sounds and ignore distractors depends on the structural properties and perceptual organization of the non target sounds. PMID- 22039337 TI - Approaches to biology teaching and learning: lesson study-building communities of learning among educators. PMID- 22039338 TI - From the National Academies. PMID- 22039339 TI - WWW. Cell biology education. PMID- 22039340 TI - Review of: PLoS biology--a freely available, open access online journal. PMID- 22039341 TI - Biology for the utilitarian. PMID- 22039343 TI - Meeting the challenge of science literacy: project 2061 efforts to improve science education. PMID- 22039344 TI - Characterization of pathogenic human MSH2 missense mutations using yeast as a model system: a laboratory course in molecular biology. AB - This work describes the project for an advanced undergraduate laboratory course in cell and molecular biology. One objective of the course is to teach students a variety of cellular and molecular techniques while conducting original research. A second objective is to provide instruction in science writing and data presentation by requiring comprehensive laboratory reports modeled on the primary literature. The project for the course focuses on a gene, MSH2, implicated in the most common form of inherited colorectal cancer. Msh2 is important for maintaining the fidelity of genetic material where it functions as an important component of the DNA mismatch repair machinery. The goal of the project has two parts. The first part is to create mapped missense mutation listed in the human databases in the cognate yeast MSH2 gene and to assay for defects in DNA mismatch repair. The second part of the course is directed towards understanding in what way are the variant proteins defective for mismatch repair. Protein levels are analyzed to determine if the missense alleles display decreased expression. Furthermore, the students establish whether the Msh2p variants are properly localized to the nucleus using indirect immunofluorescence and whether the altered proteins have lost their ability to interact with other subunits of the MMR complex by creating recombinant DNA molecules and employing the yeast 2 hybrid assay. PMID- 22039345 TI - Just-in-Time Teaching in biology: creating an active learner classroom using the Internet. PMID- 22039346 TI - Mystery of the toxic flea dip: an interactive approach to teaching aerobic cellular respiration. AB - We designed an interrupted case study to teach aerobic cellular respiration to major and nonmajor biology students. The case is based loosely on a real-life incident of rotenone poisoning. It places students in the role of a coroner who must determine the cause of death of the victim. The case is presented to the students in four parts. Each part is followed by discussion questions that the students answer in small groups prior to a classwide discussion. Successive parts of the case provide additional clues to the mystery and help the students focus on the physiological processes involved in aerobic respiration. Students learn the information required to solve the mystery by reading the course textbook prior to class, listening to short lectures interspersed throughout the case, and discussing the case in small groups. The case ends with small group discussions in which the students are given the names and specific molecular targets of other poisons of aerobic respiration and asked to determine which process (i.e., glycolysis, citric acid cycle, or the electron transport chain) the toxin disrupts. PMID- 22039347 TI - Teaching how to bridge neuroscience, society, and culture. PMID- 22039348 TI - Genetic origins of birth defects revealed by new animal model. PMID- 22039349 TI - Multifactorial origins of heart and gut defects in nipbl-deficient zebrafish, a model of Cornelia de Lange Syndrome. AB - Cornelia de Lange Syndrome (CdLS) is the founding member of a class of multi organ system birth defect syndromes termed cohesinopathies, named for the chromatin-associated protein complex cohesin, which mediates sister chromatid cohesion. Most cases of CdLS are caused by haploinsufficiency for Nipped-B-like (Nipbl), a highly conserved protein that facilitates cohesin loading. Consistent with recent evidence implicating cohesin and Nipbl in transcriptional regulation, both CdLS cell lines and tissues of Nipbl-deficient mice show changes in the expression of hundreds of genes. Nearly all such changes are modest, however- usually less than 1.5-fold--raising the intriguing possibility that, in CdLS, severe developmental defects result from the collective action of many otherwise innocuous perturbations. As a step toward testing this hypothesis, we developed a model of nipbl-deficiency in zebrafish, an organism in which we can quantitatively investigate the combinatorial effects of gene expression changes. After characterizing the structure and embryonic expression of the two zebrafish nipbl genes, we showed that morpholino knockdown of these genes produces a spectrum of specific heart and gut/visceral organ defects with similarities to those in CdLS. Analysis of nipbl morphants further revealed that, as early as gastrulation, expression of genes involved in endodermal differentiation (sox32, sox17, foxa2, and gata5) and left-right patterning (spaw, lefty2, and dnah9) is altered. Experimental manipulation of the levels of several such genes--using RNA injection or morpholino knockdown--implicated both additive and synergistic interactions in causing observed developmental defects. These findings support the view that birth defects in CdLS arise from collective effects of quantitative changes in gene expression. Interestingly, both the phenotypes and gene expression changes in nipbl morphants differed from those in mutants or morphants for genes encoding cohesin subunits, suggesting that the transcriptional functions of Nipbl cannot be ascribed simply to its role in cohesin loading. PMID- 22039350 TI - Dpp signaling activity requires Pentagone to scale with tissue size in the growing Drosophila wing imaginal disc. AB - The wing of the fruit fly, Drosophila melanogaster, with its simple, two dimensional structure, is a model organ well suited for a systems biology approach. The wing arises from an epithelial sac referred to as the wing imaginal disc, which undergoes a phase of massive growth and concomitant patterning during larval stages. The Decapentaplegic (Dpp) morphogen plays a central role in wing formation with its ability to co-coordinately regulate patterning and growth. Here, we asked whether the Dpp signaling activity scales, i.e. expands proportionally, with the growing wing imaginal disc. Using new methods for spatial and temporal quantification of Dpp activity and its scaling properties, we found that the Dpp response scales with the size of the growing tissue. Notably, scaling is not perfect at all positions in the field and the scaling of target gene domains is ensured specifically where they define vein positions. We also found that the target gene domains are not defined at constant concentration thresholds of the downstream Dpp activity gradients P-Mad and Brinker. Most interestingly, Pentagone, an important secreted feedback regulator of the pathway, plays a central role in scaling and acts as an expander of the Dpp gradient during disc growth. PMID- 22039351 TI - Regulation of nucleotide excision repair by UV-DDB: prioritization of damage recognition to internucleosomal DNA. AB - How tightly packed chromatin is thoroughly inspected for DNA damage is one of the fundamental unanswered questions in biology. In particular, the effective excision of carcinogenic lesions caused by the ultraviolet (UV) radiation of sunlight depends on UV-damaged DNA-binding protein (UV-DDB), but the mechanism by which this DDB1-DDB2 heterodimer stimulates DNA repair remained enigmatic. We hypothesized that a distinctive function of this unique sensor is to coordinate damage recognition in the nucleosome repeat landscape of chromatin. Therefore, the nucleosomes of human cells have been dissected by micrococcal nuclease, thus revealing, to our knowledge for the first time, that UV-DDB associates preferentially with lesions in hypersensitive, hence, highly accessible internucleosomal sites joining the core particles. Surprisingly, the accompanying CUL4A ubiquitin ligase activity is necessary to retain the xeroderma pigmentosum group C (XPC) partner at such internucleosomal repair hotspots that undergo very fast excision kinetics. This CUL4A complex thereby counteracts an unexpected affinity of XPC for core particles that are less permissive than hypersensitive sites to downstream repair subunits. That UV-DDB also adopts a ubiquitin independent function is evidenced by domain mapping and in situ protein dynamics studies, revealing direct but transient interactions that promote a thermodynamically unfavorable beta-hairpin insertion of XPC into substrate DNA. We conclude that the evolutionary advent of UV-DDB correlates with the need for a spatiotemporal organizer of XPC positioning in higher eukaryotic chromatin. PMID- 22039352 TI - Structure and evolution of Streptomyces interaction networks in soil and in silico. AB - Soil grains harbor an astonishing diversity of Streptomyces strains producing diverse secondary metabolites. However, it is not understood how this genotypic and chemical diversity is ecologically maintained. While secondary metabolites are known to mediate signaling and warfare among strains, no systematic measurement of the resulting interaction networks has been available. We developed a high-throughput platform to measure all pairwise interactions among 64 Streptomyces strains isolated from several individual grains of soil. We acquired more than 10,000 time-lapse movies of colony development of each isolate on media containing compounds produced by each of the other isolates. We observed a rich set of such sender-receiver interactions, including inhibition and promotion of growth and aerial mycelium formation. The probability that two random isolates interact is balanced; it is neither close to zero nor one. The interactions are not random: the distribution of the number of interactions per sender is bimodal and there is enrichment for reciprocity--if strain A inhibits or promotes B, it is likely that B also inhibits or promotes A. Such reciprocity is further enriched in strains derived from the same soil grain, suggesting that it may be a property of coexisting communities. Interactions appear to evolve rapidly: isolates with identical 16S rRNA sequences can have very different interaction patterns. A simple eco-evolutionary model of bacteria interacting through antibiotic production shows how fast evolution of production and resistance can lead to the observed statistical properties of the network. In the model, communities are evolutionarily unstable--they are constantly being invaded by strains with new sets of interactions. This combination of experimental and theoretical observations suggests that diverse Streptomyces communities do not represent a stable ecological state but an intrinsically dynamic eco-evolutionary phenomenon. PMID- 22039353 TI - Measuring the performance of vaccination programs using cross-sectional surveys: a likelihood framework and retrospective analysis. AB - BACKGROUND: The performance of routine and supplemental immunization activities is usually measured by the administrative method: dividing the number of doses distributed by the size of the target population. This method leads to coverage estimates that are sometimes impossible (e.g., vaccination of 102% of the target population), and are generally inconsistent with the proportion found to be vaccinated in Demographic and Health Surveys (DHS). We describe a method that estimates the fraction of the population accessible to vaccination activities, as well as within-campaign inefficiencies, thus providing a consistent estimate of vaccination coverage. METHODS AND FINDINGS: We developed a likelihood framework for estimating the effective coverage of vaccination programs using cross sectional surveys of vaccine coverage combined with administrative data. We applied our method to measles vaccination in three African countries: Ghana, Madagascar, and Sierra Leone, using data from each country's most recent DHS survey and administrative coverage data reported to the World Health Organization. We estimate that 93% (95% CI: 91, 94) of the population in Ghana was ever covered by any measles vaccination activity, 77% (95% CI: 78, 81) in Madagascar, and 69% (95% CI: 67, 70) in Sierra Leone. "Within-activity" inefficiencies were estimated to be low in Ghana, and higher in Sierra Leone and Madagascar. Our model successfully fits age-specific vaccination coverage levels seen in DHS data, which differ markedly from those predicted by naive extrapolation from country-reported and World Health Organization-adjusted vaccination coverage. CONCLUSIONS: Combining administrative data with survey data substantially improves estimates of vaccination coverage. Estimates of the inefficiency of past vaccination activities and the proportion not covered by any activity allow us to more accurately predict the results of future activities and provide insight into the ways in which vaccination programs are failing to meet their goals. Please see later in the article for the Editors' Summary. PMID- 22039354 TI - Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies. AB - BACKGROUND: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded. METHODS AND FINDINGS: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders. CONCLUSIONS: Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions. Please see later in the article for the Editors' Summary. PMID- 22039355 TI - Speed and convenience aren't everything with diagnostics. PMID- 22039356 TI - STrengthening the Reporting of OBservational studies in Epidemiology--Molecular Epidemiology (STROBE-ME): an extension of the STROBE Statement. PMID- 22039358 TI - Multi-Level Ewald: A hybrid multigrid / Fast Fourier Transform approach to the electrostatic particle-mesh problem. AB - We present a new method for decomposing the one convolution required by standard Particle-Particle Particle-Mesh (P(3)M) electrostatic methods into a series of convolutions over slab-shaped subregions of the original simulation cell. Most of the convolutions derive data from separate regions of the cell and can thus be computed independently via FFTs, in some cases with a small amount of zero padding so that the results of these sub-problems may be reunited with minimal error. A single convolution over the entire cell is also performed, but using a much coarser mesh than the original problem would have required. This "Multi Level Ewald" (MLE) method therefore requires moderately more FFT work plus the tasks of interpolating between different sizes of mesh and accumulating the results from neighboring sub-problems, but we show that the added expense can be less than 10% of the total simulation cost. We implement MLE as an approximation to the Smooth Particle Mesh Ewald (SPME) style of P(3)M, and identify a number of tunable parameters in MLE. With reasonable settings pertaining to the degree of overlap between the various sub-problems and the accuracy of interpolation between meshes, the errors obtained by MLE can be smaller than those obtained in molecular simulations with typical SPME settings. We compare simulations of a box of water molecules performed with MLE and SPME, and show that the energy conservation, structural, and dynamical properties of the system are more affected by the accuracy of the SPME calculation itself than by the additional MLE approximation. We anticipate that the MLE method's ability to break a single convolution into many independent sub-problems will be useful for extending the parallel scaling of molecular simulations. PMID- 22039357 TI - Universal definition of loss to follow-up in HIV treatment programs: a statistical analysis of 111 facilities in Africa, Asia, and Latin America. AB - BACKGROUND: Although patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition. METHODS AND FINDINGS: At a set "status classification" date, patients were categorized as either "active" or "LTFU" according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities-representing 180,718 patients from 19 countries-were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173 181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%-7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean=150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean=1.2%, 95% CI: 1.0%-1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean=19.9%, 95% CI: 19.1%-21.7%). CONCLUSIONS: Based on this evaluation, we recommend the adoption of >=180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide. Please see later in the article for the Editors' Summary. PMID- 22039359 TI - Calibration of DFT Functionals for the Prediction of Fe Mossbauer Spectral Parameters in Iron-Nitrosyl and Iron-Sulfur Complexes: Accurate Geometries Prove Essential. AB - Six popular density functionals in conjunction with the conductor-like screening (COSMO) solvation model have been used to obtain linear Mossbauer isomer shift (IS) and quadrupole splitting (QS) parameters for a test set of 20 complexes (with 24 sites) comprised of nonheme nitrosyls (Fe-NO) and non-nitrosyl (Fe-S) complexes. For the first time in an IS analysis, the Fe electron density was calculated both directly at the nucleus, rho(0)(N), which is the typical procedure, and on a small sphere surrounding the nucleus, rho(0)(S), which is the new standard algorithm implemented in the ADF software package. We find that both methods yield (near) identical slopes from each linear regression analysis but are shifted with respect to rho(0) along the x-axis. Therefore, the calculation of the Fe electron density with either method gives calibration fits with equal predictive value. Calibration parameters obtained from the complete test set for OLYP, OPBE, PW91, and BP86 yield correlation coefficients (r(2)) of approximately 0.90, indicating that the calibration fit is of good quality. However, fits obtained from B3LYP and B3LYP* with both Slater-type and Gaussian-type orbitals are generally found to be of poorer quality. For several of the complexes examined in this study, we find that B3LYP and B3LYP* give geometries that possess significantly larger deviations from the experimental structures than OLYP, OPBE, PW91 or BP86. This phenomenon is particularly true for the di- and tetranuclear Fe complexes examined in this study. Previous Mossbauer calibration fit studies using these functionals have usually included mononuclear Fe complexes alone, where these discrepancies are less pronounced. An examination of spin expectation values reveals B3LYP and B3LYP* approach the weak-coupling limit more closely than the GGA exchange-correlation functionals. The high degree of variability in our calculated S(2) values for the Fe-NO complexes highlights their challenging electronic structure. Significant improvements to the isomer shift calibrations are obtained for B3LYP and B3LYP* when geometries obtained with the OLYP functional are used. In addition, greatly improved performance of these functionals is found if the complete test set is grouped separately into Fe NO and Fe-S complexes. Calibration fits including only Fe-NO complexes are found to be excellent, while those containing the non-nitrosyl Fe-S complexes alone are found to demonstrate less accurate correlations. Similar trends are also found with OLYP, OPBE, PW91, and BP86. Correlations between experimental and calculated QSs were also investigated. Generally, universal and separate Fe-NO and Fe-S fit parameters obtained to determine QSs are found to be of good to excellent quality for every density functional examined, especially if [Fe(4)(NO)(4)(MU(3)-S)(4)]( ) is removed from the test set. PMID- 22039361 TI - Accelerated Profile HMM Searches. AB - Profile hidden Markov models (profile HMMs) and probabilistic inference methods have made important contributions to the theory of sequence database homology search. However, practical use of profile HMM methods has been hindered by the computational expense of existing software implementations. Here I describe an acceleration heuristic for profile HMMs, the "multiple segment Viterbi" (MSV) algorithm. The MSV algorithm computes an optimal sum of multiple ungapped local alignment segments using a striped vector-parallel approach previously described for fast Smith/Waterman alignment. MSV scores follow the same statistical distribution as gapped optimal local alignment scores, allowing rapid evaluation of significance of an MSV score and thus facilitating its use as a heuristic filter. I also describe a 20-fold acceleration of the standard profile HMM Forward/Backward algorithms using a method I call "sparse rescaling". These methods are assembled in a pipeline in which high-scoring MSV hits are passed on for reanalysis with the full HMM Forward/Backward algorithm. This accelerated pipeline is implemented in the freely available HMMER3 software package. Performance benchmarks show that the use of the heuristic MSV filter sacrifices negligible sensitivity compared to unaccelerated profile HMM searches. HMMER3 is substantially more sensitive and 100- to 1000-fold faster than HMMER2. HMMER3 is now about as fast as BLAST for protein searches. PMID- 22039362 TI - Discovery of an ebolavirus-like filovirus in europe. AB - Filoviruses, amongst the most lethal of primate pathogens, have only been reported as natural infections in sub-Saharan Africa and the Philippines. Infections of bats with the ebolaviruses and marburgviruses do not appear to be associated with disease. Here we report identification in dead insectivorous bats of a genetically distinct filovirus, provisionally named Lloviu virus, after the site of detection, Cueva del Lloviu, in Spain. PMID- 22039363 TI - Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population. AB - Pathogens are believed to drive genetic diversity at host loci involved in immunity to infectious disease. To date, studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC); the role of genetic variation elsewhere in the genome as a basis for variation in pathogen resistance has rarely been explored in natural populations. Cytokines are signalling molecules with a role in many immunological and physiological processes. Here we use a natural population of field voles (Microtus agrestis) to examine how genetic diversity at a suite of cytokine and other immune loci impacts the immune response phenotype and resistance to several endemic pathogen species. By using linear models to first control for a range of non-genetic factors, we demonstrate strong effects of genetic variation at cytokine loci both on host immunological parameters and on resistance to multiple pathogens. These effects were primarily localized to three cytokine genes (Interleukin 1 beta (Il1b), Il2, and Il12b), rather than to other cytokines tested, or to membrane-bound, non-cytokine immune loci. The observed genetic effects were as great as for other intrinsic factors such as sex and body weight. Our results demonstrate that genetic diversity at cytokine loci is a novel and important source of individual variation in immune function and pathogen resistance in natural populations. The products of these loci are therefore likely to affect interactions between pathogens and help determine survival and reproductive success in natural populations. Our study also highlights the utility of wild rodents as a model of ecological immunology, to better understand the causes and consequences of variation in immune function in natural populations including humans. PMID- 22039364 TI - Development and validation of a standardized protocol to monitor human dietary exposure by metabolite fingerprinting of urine samples. AB - Conventional tools for measuring dietary exposure have well recognized limitations. Measurement of food-derived metabolites in biofluids provides an alternative approach and our aim was to develop an experimental protocol which ensures that extraneous variability does not obscure metabolic signals from ingested foods. Healthy adults consumed a standardized meal in the evening before each test day and collected pooled overnight urine. On each test day of three different studies, urine was collected in the fasted state and at different time points after consumption of a standardized breakfast. Metabolite fingerprinting of samples using Flow Infusion Electrospray-Ionization Mass Spectrometry followed by multivariate data analysis showed strong discrimination between overnight, fasting and postprandial samples, in each study separately and when data from the three studies were pooled. Such differences were robust and highly reproducible within individuals on separate occasions. Urine volume was an efficient data normalization factor for metabolite fingerprinting data. Postprandial urines had a stable chemical composition over a period of 2-4 h after eating a standardized breakfast, suggesting that there is a flexible time window for urine collection. Fasting urine samples provided a stable baseline for universal comparisons with postprandial samples. A dietary exposure biomarker discovery protocol was validated by demonstrating that top-ranked signals discriminating between fasting and 2-4 h postprandial urine samples could be linked to metabolites abundant in some components of the standardized breakfast. We conclude that the protocol developed will have value in the search for biomarker leads of dietary exposure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-011-0289-0) contains supplementary material, which is available to authorized users. PMID- 22039365 TI - LC/MS profiling of flavonoid glycoconjugates isolated from hairy roots, suspension root cell cultures and seedling roots of Medicago truncatula. AB - Hairy roots and suspension cell cultures are commonly used in deciphering different problems related to the biochemistry and physiology of plant secondary metabolites. Here, we address about the issue of possible differences in the profiles of flavonoid compounds and their glycoconjugates derived from various plant materials grown in a standard culture media. We compared profiles of flavonoids isolated from seedling roots, hairy roots, and suspension root cell cultures of a model legume plant, Medicago truncatula. The analyses were conducted with plant isolates as well as the media. The LC/MS profiles of target natural products obtained from M. truncatula seedling roots, hairy roots, and suspension root cell cultures differed substantially. The most abundant compounds in seedlings roots were mono- and diglucuronides of isoflavones and/or flavones. This type of glycosylation was not observed in hairy roots or suspension root cell cultures. The only recognized glycoconjugates in the latter samples were glucose derivatives of isoflavones. Application of a high-resolution mass spectrometer helped evaluate the elemental composition of protonated molecules, such as [M + H](+). Comparison of collision-induced dissociation MS/MS spectra registered with a quadrupole time-of-flight analyzer for tissue extracts and standards allowed us to estimate the aglycone structure on the basis of the pseudo-MS(3) experiment. Structures of these natural products were described according to the registered mass spectra and literature data. The analyses conducted represent an overview of flavonoids and their conjugates in different types of plant material representing the model legume, M. truncatula. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306 011-0287-2) contains supplementary material, which is available to authorized users. PMID- 22039366 TI - Stimulatory Effect of beta-glucans on Immune Cells. AB - beta-Glucans are naturally occurring polysaccharides that are produced by bacteria, yeast, fungi, and many plants. Although their pharmacological activities, such as immunomodulatory, anti-infective and anti-cancer effects, have been well studied, it is still unclear how beta-glucans exert their activities. However, recent studies on the beta-glucan receptors shed some light on their mechanism of action. Since beta-glucans have large molecular weights, they must bind surface receptors to activate immune cells. In this review, we summarize the immunopharmacological activities and the potential receptors of beta-glucans in immune cells. PMID- 22039367 TI - Activin A Stimulates Mouse APCs to Express BAFF via ALK4-Smad3 Pathway. AB - BACKGROUND: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. METHODS: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. RESULTS: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. CONCLUSION: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway. PMID- 22039368 TI - Identification of CCL1 as a Gene Differentially Expressed in CD4 T Cells Expressing TIM-3. AB - BACKGROUND: T cell immunoglobulin mucin containing molecule (TIM)-3 is expressed in differentiated Th1 cells and is involved in the suppression of the cytokine production by these cells. However, the regulation of the expression of other T cell genes by TIM-3 is unclear. Herein, we attempted to identify differentially expressed genes in cells abundantly expressing TIM-3 compared to cells with low expression of TIM-3. METHODS: TIM-3 overexpressing cell clones were established by transfection of Jurkat T cells with TIM-3 expression vector. For screening of differentially expressed genes, gene fishing technology based on reverse transcription-polymerase chain reaction (RT-PCR) using an annealing control primer system was used. The selected candidate genes were validated by semi quantitative and real-time RT-PCR. RESULTS: The transcription of TIMP-1, IFITM1, PAR3 and CCL1 was different between TIM-3 overexpressing cells and control cells. However, only CCL1 transcription was significantly different in cells transiently transfected with TIM3 expression vector compared with control cells. CCL1 transcription was increased in primary human CD4(+) T cells abundantly expressing TIM-3 but not in cells with low expression of TIM-3. CONCLUSION: CCL1 was identified as a differentially transcribed gene in TIM-3-expressing CD4(+) T cells. PMID- 22039369 TI - The Anti-tumor Activity of Vitamin C via the Increase of Fas (CD95) and MHC I Expression on Human Stomach Cancer Cell Line, SNU1. AB - BACKGROUND: It is already known that high concentration of vitamin C induces apoptosis on tumor cells. However, there is no report regarding the function of vitamin C on the modulation of immune susceptibility of cancer. Therefore, we investigated whether vitamin C can modulate immune susceptibility of tumor cells, especially on the induction of Fas-mediated apoptosis. METHODS: First, the optimal concentration of vitamin C, which cannot induce damages on tumor cells for 36 hrs. We found that 2 mM of vitamin C did not show harmful effect. In addition, the optimal concentration of agonistic anti-Fas Abs for 18 hrs was examined. RESULTS: As a result, 400 ng/ml of agonistic anti-Fas Abs did not induce apoptosis on tumor cells. Next, we tried to find the effect of 2 mM of vitamin C on the modulation of the susceptibility to agonistic anti-Fas Abs. When tumor cells were cultured with 400 ng/ml of agonistic anti-Fas Abs for 18 hrs, after pre-treatment with 2 mM of vitamin C for 24 hrs, viability of cells was decreased. Interestingly, we found that the expression of Fas (CD95) and MHC class I was increased by the treatment of vitamin C. CONCLUSION: Taken together, vitamin C increases the susceptibility of tumor cells to anti-Fas Abs and the expression of Fas (CD95) and MHC class I on tumor cells. PMID- 22039371 TI - IGF-I Exerts an Anti-inflammatory Effect on Skeletal Muscle Cells through Down regulation of TLR4 Signaling. AB - Although exercise-induced growth factors such as Insulin-like growth factor-I (IGF-I) are known to affect various aspects of physiology in skeletal muscle cells, the molecular mechanism by which IGF-I modulates anti-inflammatory effects in these cells is presently unknown. Here, we showed that IGF-I stimulation suppresses the expression of toll-like receptor 4 (TLR4), a key innate immune receptor. A pharmacological inhibitor study further showed that PI3K/Akt signaling pathway is required for IGF-I-mediated negative regulation of TLR4 expression. Furthermore, IGF-I treatment reduced the expression of various NF kappaB-target genes such as TNF-alpha and IL-6. Taken together, these findings indicate that the anti-inflammatory effect of exercise may be due, at least in part, to IGF-I-induced suppression of TLR4 and subsequent downregulation of the TLR4-dependent inflammatory signaling pathway. PMID- 22039370 TI - Recombinant TAT-CD137 Ligand Cytoplasmic Domain Fusion Protein Induces the Production of IL-6 and TNF-alpha in Peritoneal Macrophages. AB - BACKGROUND: The ligand for CD137 (CD137L; also called 4-1BBL) is mainly expressed on activated APCs such as dendritic cells, B cells and macrophages. Even though CD137L functions as a trigger of the CD137 signaling pathway for T cell activation and expansion, engagement of CD137L can deliver a signal leading to the production of proinflammatory cytokines in macrophages. METHODS: We generated cell-permeable TAT-CD137L cytoplasmic domain fusion protein (TAT-CD137Lct) and examined its ability to initiate the CD137L reverse signaling pathway. RESULTS: Treatment of TAT-CD137Lct induced the production of high levels of IL-6 and TNF alpha mRNAs and proteins in peritoneal macrophages. TAT-CD137Lct increased phosphorylation of Erk, p38 MAPK and Jnk, and activated transcription factors C/EBP and CREB. However, TAT-CD137Lct did not visibly affect the degradation of the inhibitor of NF-kB (IkBalpha). We further demonstrated that JNK activation was required for TAT-CD137Lct-induced production of TNF-alpha, while activation of Erk and p38 MAPK were involved in IL-6 and TNF-alpha production. CONCLUSION: Our results suggest that TAT-CD137Lct is an effective activator for the CD137L reverse signaling pathway. PMID- 22039372 TI - Association of Allelic Variation in Genes Mediating Aspects of Energy Homeostasis with Weight Gain during Administration of Antipsychotic Drugs (CATIE Study). AB - Antipsychotic drugs are widely used in treating schizophrenia, bipolar disorder, and other psychiatric disorders. Many of these drugs, despite their therapeutic advantages, substantially increase body weight. We assessed the association of alleles of 31 genes implicated in body weight regulation with weight gain among patients being treated with specific antipsychotic medications in the clinical antipsychotic trials in intervention effectiveness study, we found that rs2237988 in Potassium Channel Inwardly Rectifying Subfamily J Member 11 (KCNJ11), rs13269119 in Solute carrier family 30 member 8 (SLC30A8), and rs9922047 in fat mass and obesity associated (FTO) were associated with percent weight gain. We also observed the significant interaction of rs11643744 by treatment effect on the weight gain. PMID- 22039373 TI - The effect of reflexotherapy on patients' vital signs before coronary artery bypass graft surgery. AB - BACKGROUND: Medical operation is an anxious factor that causes physiological reactions in body which consequently increases respiratory rate, heart rate and blood pressure. The aim of this study is assessing the effect of reflexotherapy on vital signs of patients before coronary artery bypass surgery in Shahid Chamran hospital of Isfahan. METHODS: Fifty volunteer patients candidated for coronary artery bypass surgery were enrolled in this clinical trial. They were divided in two (control and treatment) groups. Vital signs were measured pre and post 30 minutes reflexotherapy in treatment group. Vital signs were also measured in patients in control group at the same condition of the treatment group, but reflexotherapy was not performed. RESULTS: The mean differences of vital signs was not significant in control and treatment groups at the baseline. But post reflexotherapy intervention, systolic and diastolic blood pressure lowered significantly in the treatment group in comparison with control group (p < 0.05). No significant changes were observed for other vital sign. CONCLUSIONS: The findings of the study shows that reflexotherapy is a safe, effective, cheep nursing intervention in reducing systolic and diastolic blood pressure of patients before coronary artery bypass surgery. PMID- 22039374 TI - Experiences of nursing students in caring of patients in source isolation. AB - BACKGROUND: Infectious disease control is one of the important components of patient care which can assist in reducing morbidity and mortality. Source isolation is one of the strategies that have used in order to prevent from the spread of contagious infectious diseases. Since nursing student should be able to do the caring in source isolation patients after learning the principles, it's necessary to assess the students' perception of caring for this client group in order to prepare them for the role of caring. METHODS: This is a qualitative phenomenological study; its participants were selected with maximum variation by purposed sampling from first to fourth year nursing and midwifery students of Isfahan School of Nursing and Midwifery. The students used to do the patient caring during the clinical internship. The sampling done until 10 interview data saturation was obtained. In order to collect data, researcher used depth interview method. Data analysis was performed by seven-stage Collaizzi method. RESULTS: The findings of this study included 6 main concept (themes) from participants' experiences as following: 1. Stressor agents of caring, 2. Response to stress, 3. Care requirments, 4. Care provider performance, 5. Consequence of care, and 6. Improper caring. CONCLUSIONS: Providing educational programs in terms of isolated patients can reduce anxiety in students which this can lead to more control and prevent the spread of infectious diseases. In addition, studying about patients' needs can be useful for improving practical interventions and clinical care. PMID- 22039375 TI - Psychiatric team's experience of working in psychiatric wards. AB - BACKGROUND: Psychiatric team plays an important role in treating and taking care of psychiatric patients. Using this team's experience seems necessary for enhancing care services. The aim of this study was to assess psychiatric team's experience of working in different psychiatric groups. METHODS: This is a qualitative study with phenomenological approach. Samples were chosen using purposive sampling method. Samples included 10 personnel from psychiatric wards of 4 hospitals in Isfahan city in 2007. Data was gathered using deep interviews which were recorded on tapes. Data was analyzed using Colaizzi's seven steps method. RESULTS: Results from participants' experiences were summarized in 3 main concepts: "communication", "ability" and "conflict"; and 5 sub concepts: "cooperation", "self acknowledgement", "hope", "qualification" and "multiple roles". CONCLUSIONS: Results of this study could be used in future programming to enhance care services for psychiatric patients in hospitals. PMID- 22039376 TI - Designing the Vocal Alarm and improving medical ventilator. AB - BACKGROUND: Today, as many as 1.5 million Americans use ventilators once in a year. Response to mechanical ventilation alarms remains to be one of the most challenging tasks facing physicians, nurses or other medical personnel in the ICU. In the present study we aimed to compare the response times to "vocal alarms" and "visual or audible ones". METHODS: In the present study we developed a system to evaluate the "Vocal Alarm" and improve the medical ventilator "Benet 7200 Alarms" with it. Ventilator generates the alarms when patient has any problem. The time of Activation & Deactivation is recorded. The survey was done in central ICU for six days, 3 days with vocal alarm, and 3days with "Beep" alarms and detected Alarm events then recorded seventy-two hours of data for each type of alarms. All of events information saved in the memory and SPSS was used to determine difference between two types of alarms. RESULTS: On the average, the duration of the ventilator alarms activation were 33 +/- 21 seconds for vocal alarms and 60 +/- 46 for audible "Beep" alarms. The response times for vocal alarms were significantly lower (P = 0.001). CONCLUSIONS: The response times for normal "Beep" alarms were longer than vocal alarms. PMID- 22039377 TI - Knowledge, awareness, attitudes and practice about hypertension in hypertensive patients referring to public health care centers in Khoor & Biabanak. AB - BACKGROUND: Hypertension is one of the most crucial health problems and the most common chronic disease in developed and underdeveloped countries. It is called the silent killer which is usually diagnosed incidentally. Although hypertension is a preventable and treatable condition but without treatment it leads to serious and life threatening complications such as heart, kidney and brain disorders which in most cases result in patient's disability. Prevention, plays significant role in controlling this disease which is achieved by increasing the knowledge and awareness of the public and changing their attitude and practice. METHODS: A cross-sectional, correlation-descriptive study was conducted in one stage, by one group. Two hundred and thirty four patients were recruited by random sampling among hypertensive patients referring to public health care centers in Khoor & Biabanak in Isfahan province, IRAN. Data gathering was carried out with a questionnaire. RESULTS: Our findings indicate that there is significant relationship between awareness and knowledge; awareness and attitude; awareness and practice. There is no significant relationship between knowledge and attitude or knowledge and practice. In addition, there is a significant relationship between attitude and practice of the patients. CONCLUSIONS: Although patients relatively had high awareness, knowledge, attitude and practice about their disease but their hypertension was not still under control. Several barriers are associated with uncontrolled hypertension particularly treatment related barriers. Findings suggest further studies to determine new effective strategies to solve this problem. PMID- 22039378 TI - Sources of occupational stress and coping strategies among nurses who work in Admission and Emergency Departments of Hospitals related to Shiraz University of Medical Sciences. AB - BACKGROUND: Occupational stress is a recognized problem in health care workers. Nursing has been identified as an occupation that has high levels of stress. This study aimed to investigate the sources of job stress and the adopted coping strategies of nurses who were working in an Accident and emergency department. METHODS: In this descriptive survey ninety emergency ward nurses from three large teaching hospitals in Shiraz were involved. The data was collected through a self administered questionnaire to identify the sources of job stress and nurse's profile and Lazarus standard questionnaires to determine the types of coping strategies. RESULTS: The greatest proportion of respondents was women (86.7%), between 23-50 years old with less than 5 years of experience (56.7%). The following stressors were identified: problems related to physical environment, work load, dealing with patients or their relatives and handling their anger, being exposed to health and safety hazards, lack of support by nursing administrators, absence of the corresponding physician in the emergency room and lack of equipment. The most common strategy used by nurses was self-controlling and Positive Reappraisal and the least common strategy was accepting the responsibility. In this study large proportion of nurses used an emotion-focused strategy while Problem-focused approaches were generally less used. CONCLUSIONS: It was concluded that coping skills, positive reappraisal and self-controlling are extremely important for emergency department nurses. PMID- 22039379 TI - Prevalence of HBsAg and high-risk behaviors in pregnant women rerring to Urban Health Centers in Isfahan province. AB - BACKGROUND: About 5% of the world population are carriers of the hepatitis B virus which is not the same in different areas of the world. Iran, with a rate of 2-3%, is among the countries with average prevalence. The aim of this study was to determine the prevalence of HBsAg and its associated factors in pregnant women who referred to urban health centers in Isfahan Province. METHODS: This was a descriptive study conducted on 1078 pregnant women who had referred to the urban health centers of Isfahan, Borkhar, Meymeh, Khomeini Shahr, Lenjan and Najaf Abad in 2009 in order to register their physical condition and receive pregnancy care. Random sampling method by quota was done. First, a questionnaire including demographic characteristics and history of high-risk behaviors in mothers and their husbands was completed. Then, a blood sample was taken and evaluated for the HB virus surface antigen. Finally, the data was analyzed using SPSS software, Chi-square, Fisher and Logistic Regression tests. RESULTS: HB virus surface antigen was traced in the serum of 0.5% of the participants. The average age of subjects was 26.1+/- 4.9 (mean+/-sd) years old and the average pregnancy number was 1.79 + 1.0 (mean+/-sd). Using Fisher's test as well as logistic regression test and based on the previous history of high-risk sexual behaviors and tattooing, a significant difference was observed between the two groups with positive and negative HBsAg (p <= 0.05). CONCLUSIONS: Instructing the target groups and close monitoring of the high-risk centers such as beauty shops, tattooing centers and etc, and also staff training on how to use disposable and sterilized equipments have to be accomplished at the right time. PMID- 22039380 TI - The effect of Ti Chi exercise on the sleep quality of the elderly residents in Isfahan, Sadeghieh elderly home. AB - BACKGROUND: Sleep disturbances are common among older adults. Recently there is much interest in complementary and alternative medicine (CAM) from the population in general, and the elderly are no exception. Tai Chi exercise as a CAM can be performed by older adults. The purpose of this study was to evaluate the effects of Tai Chi Exercise on sleep quality of elderly residents in Sadeghiyeh elderly care home. METHODS: In this Clinical Trial, 62 older subjects aged older than 65 years residents of elderly home in Isfahan were studied. They randomized in two experimental and control groups. The intervention was the Tai Chi Exercise sessions were held three times per week for 12 weeks. Duration of exercise was 5 minutes at first session which gradually increased to 20 to 25 minutes by the midpoint of intervention. The Pittsburgh Sleep Quality Index (PSQI) was used for pre and post evaluation of older adult sleep quality. Data analyzed using the SPSS(14) software. RESULTS: There were no differences in demographic characteristics or psychological variables between two groups. Mean age of studied subjects in experimental and control groups was 68.74(5.48) and 69.42(5.34), respectively. In the Tai Chi group sleep quality was improved significantly with decrease in PSQI global score. In control group sleep quality was not changed significantly. At the end of study, mean differences of PSQI global score between two groups different significantly. CONCLUSIONS: Our finding is coherent with other studies in this field indicated that the Tai Chi Exercise can have a significant effect on sleep quality in older adults. PMID- 22039381 TI - The effect of massage therapy on blood pressure of women with pre-hypertension. AB - BACKGROUND: Prehypertension is considered as a cardiovascular disease predicator. Management of prehypertension is an appropriate objective for clinicians in a wide range of medical centers. Treatment of prehypertension is primarily non pharmacological, one of which is massage therapy that is used to control the blood pressure. This study aimed to evaluate the effect of Swedish massage (face, neck, shoulders and chest) on blood pressure (BP) of the women with prehypertension. METHODS: This was a single-blind clinical trial study. Fifty prehypertensive women selected by simple random sampling which divided into control and test groups. The test group (25 patients) received Swedish massage 10 15 min, three times a week for 10 sessions and the control groups (25 patients) also were relaxed at the same environment with receiving no massage. Their BP was measured before and after each session. Analyzing the data was done using descriptive and inferential statistical methods (chi square, Mann-Whitney, paired t-test and student t-test) through SPSS software. RESULTS: The results indicated that mean systolic and diastolic blood pressure in the massage group was significantly lower in comparison with the control group (p < 0.001). CONCLUSIONS: Findings of the study indicated that massage therapy was a safe, effective, applicable and cost-effective intervention in controlling BP of the prehypertension women and it can be used in the health care centers and even at home. PMID- 22039382 TI - The Effect of self-care on the lives of children suffering from acute lymphocytic leukemia. AB - BACKGROUND: Acute lymphocytic leukemia is one of the common cancers of childhood and currently, 80 percent of these children survive more than 5 years by getting the right treatment. Since long-term treatment is painful and invasive, preventing the side effects and their influence on quality of life is an important issue which introduces consideration for self-care. Consequently, the present study was conducted in 2007-2008 about the effects of self-care on the lives of children suffering from acute lymphocytic leukemia, referring to treatment centers in Isfahan City. METHODS: The present study was a two-staged, two-group clinical trial. 48 children aging 5-18 and suffering from acute lymphocytic leukemia were selected through convenient sampling method and the training program was administered before them and afterwards, they were divided randomly into two groups of experiment (n = 24) and control (n = 24). The General Scale and Cancer Scale Quality of Life Identification Questionnaires were used to define the quality of life of the children. The validity and reliability of the questionnaire were in turn defined by content validity method and Cronbach's alpha test. The experiment group received the self-care checklist after training and was controlled and examined for 3 months. The pre-and-post self care Quality of Life Questionnaire were both filled out in both groups and accordingly, the SPSS software, independent t test, chi-square and paired t tests were used to analyze the data. RESULTS: The findings of the study showed that both groups were homogeneous by virtue of influential factors on quality of life, like age, gender, type, stage and duration of treatment (p > 0.05). There was no significant difference between the experiment and control groups' quality of life average scores before administering the self-care training program. The results of paired-t test in the experiment group after administering the self-care program showed a significant difference in General and Cancer Scale Questionnaires Quality of Life with that before administering the program, while no significant difference was observed in the control group. Also, the independent t-test showed a significant difference in the average of quality of life score shift after administering the self care between the experiment and control groups. CONCLUSIONS: Quality of life improved after administering self care training program in the experiment group while it did not improve in the control group and even the increase in average score of quality of life in Cancer Scale in this group was an indicator of an increase in problems related to disease, treatment and care. The results of this study showed the positive effects of administering self-care on the quality of life of children suffering from acute lymphocytic leukemia. PMID- 22039383 TI - Dissatisfaction with contraceptive methods. AB - BACKGROUND: Almost two thirds of Iranians eligible for using contraceptive methods use these methods. Their dissatisfaction with the methods would directly and indirectly affect the quality of family planning services and would bring about detrimental results for the service recipients and consequently for other family members. Therefore, identification and evaluation of the factors leading to dissatisfaction with contraceptive methods can help the authorities responsible for family planning services to provide some solutions to increase satisfaction with these methods. METHODS: This research was a qualitative phenomenological study. The study population consisted of the women using intrauterine device (IUD) or contraceptive pills only as contraception, referred to 14-Masoum, Amir Hamzeh, Ebn-e Sina, Shahid Motamed, and Navab Safavi clinical centers. Sampling was goal-based, and 14 individuals participated in the study. Data collection was carried out in four months using deep interview. Data analysis was performed using seven-step Colaizzi's method. RESULTS: The findings of the interviews were assigned 104 codes categorized into three groups; 1- physical and psychological harms experienced by the method, 2- the shortcomings of the methods, and 3- continuation in spite of dissatisfaction with the method. CONCLUSIONS: According to the results, the users of contraceptive methods would have some experiences, which lead to their dissatisfaction with the methods. Since dissatisfaction with the methods will result in a decrease in continuation of use of the methods or discontinuation of the method, providing some policies to increase the satisfaction with contraceptive methods can cause more effective use of the methods and continuation of their use. PMID- 22039384 TI - The relationship between family planning methods, individual hygiene, and fertility with vaginal infections among the women referring to selected health centers in Isfahan city. AB - BACKGROUND: With regard to the high commonality of vaginal infections among pregnancy-age women, especially gardnerella, candidiasis vaginitis, trichomonal vaginitis and chlamydia and by attending to this fact that these infections have a high cost, including the medical expenses and other services like missing working hours and bear a negative effect on the life quality of women as influential individuals in family and society, we decided to examine the commonality of some of these infections and their related factors among women referring to selected health centers in Isfahan City. METHODS: This research was of an analytical-descriptive type conducted on 266 samples referred to the midwifery unit of selected health centers in Isfahan City due to one of the common vaginal infections (gardnerella, candidiasis vaginitis, trichomonal vaginitis and chlamydia). The collection of data was carried out via conducting interview with women and filling out the researcher-made questionnaire with close ended answers (38 questions) and open-ended answers (25 questions). Data analysis was done by descriptive and analytical statistics (variance analysis and chi square test). RESULTS: The findings of the study showed a significant relationship (p = 0.04) between suffering from different kinds of vaginal infection and fertility factors (the treatment record of the spouse). But, there was no significant statistical relationship between suffering from these infections and delivery type, period regulation, seeing stains and the pregnancy prevention type. Meanwhile, a significant relationship was found between suffering from vaginitis and demographic and individual factors like women's job (p=0.001), their educational level (p = 0.006), body mass index (p = 0.01) and their weight (p = 0.02). However, no significant relationship was found between suffering from common vaginal infections and individual health factors. CONCLUSIONS: With regard to the research findings, knowledge of the factors related to vaginal infection, including the fertility factors, can be instrumental in preventing and reducing the suffering from these infections. Therefore, training related to mothers' educational level and consulting with women for knowing the susceptibility factors like the effect of weight, attending to mothers' professional issues and prevention methods by following individual and sexual health-related issues by men and women can reduce the rate of suffering from these infections and promote the health level of mothers and hence, the society's health status. PMID- 22039385 TI - Effect of end-of-life care education on the attitudes of nurses in infants' and children's wards. AB - BACKGROUND: Infants palliative care becomes an important aspect of nursing when providing welfare and promoting children's life quality are the objectives of care. The number of children with life threatening diseases has increased alongside the developments in technology and medical treatment in medicine. It is a pure fact that our attitudes are related to our behaviors and performances. This research was conducted with the aim of assessing the effect of intensive course of children's palliative care on the attitudes of children and infants' nurses in Isfahan University of Medical Sciences. METHODS: This was a quasi experimental, two-group and two-stage study in which 56 nurses working at Infants' and children's wards who met inclusion criteria were divided into experiment and control groups. The participants of experiment group attended in the infants' palliative care training course which lasted for 3 weeks. A reliable and already validated questionnaire of Infants and Children Wards Nurses' Attitudes Regarding the Dying Children was used before and after training. RESULTS: There was no significant difference between the two groups regarding demographic characteristics, except for marital status which was found the study findings were not confounded by it. There was a significant difference between mean test and re-test scores in the experiment group and also between the mean scores of control and experiment groups after training. There was no significant difference between mean scores before and after training in the control group. CONCLUSIONS: End-of-life children care is one of the issues in modern medicine which has not gained a definite status in Iran. It is hoped that nurses would be the forerunners of this modern science in Iran. PMID- 22039386 TI - The comparative examination of the effect of two oxytocin administration methods of labor induction on labor duration stages. AB - BACKGROUND: Oxytocin is the most consumed medication in modern midwifery. The consumption of oxytocin in inducing and strengthening delivery in delivery wards requires an efficient method for making use of this medication with maximum effect and minimum side effects. In this regard, this study has been conducted aiming at comparing the effect of two methods of prescribing oxytocin in inducing delivery on the duration of stages. METHODS: The present study is of a clinical trial kind with three-blinded parties which was conducted in 2010 on 120 research volunteers who had the inclusion criteria. The samples were randomly assigned into two groups of control and experiment. The data collection means consisted of a questionnaire and a checklist. In order to analyze the data, the SPSS software, version 17, Student T-test and Chi-square test were used. RESULTS: There was no statistically significant difference between two groups regarding the duration of the first and the first stages and the active phase. The duration of the third stage of delivery was shorter than the group which had stopped using oxytocin at the active phase. There has been no significant difference between the mean of oxytocin dosage from the initiation of the delivery induction till the active phase. The mean of oxytocin dosage has been significantly different between two groups during all stages of delivery so much so that this rate has been lower in the experiment group. CONCLUSIONS: The results of the data analysis show that the continuation of oxytocin after the active phase not only does not have any advantage regarding the shortening of duration of stages and its cutting but also it leads to a decrease in the consumption dosage of oxytocin in the active phase and the second stage of delivery and on the other hand leads to a decrease in the side effects of the medication on mother and infant. PMID- 22039387 TI - Reviewing the effect of nursing interventions on delirious patients admitted to intensive care unit of neurosurgery ward in Al-Zahra Hospital, Isfahan University of Medical Sciences. AB - BACKGROUND: Disease is an abnormal process that affects all aspects of the human life. The hospital environment and particularly the intensive care unit (ICU) causes stress in the patient and hi/her family. Delirium, due to its sudden onset and startle, unconsciousness, memory impairment, illusion and dynamic or sedentary behaviors, is known as one of the stressor agents. Despite its high prevalence and the high cost complications such as long term mechanical ventilation, hospital pneumonia, pressure ulcer, prolongation of hospitalization in the hospital or the intensive care units, performance reduction and increase in mortality, this disorder remains unknown in most cases. In line with the other treatment team members, nurses should also participate in controlling the discountable factors, helping patients to cope with uncontrollable factors and using pharmacological methods to manage the delirium and feature their own unique capacity more through quick recognition, reviewing the causes and providing scientific care in improving the quality of patient care and improving the patients' health status. Hence, this study aimed to review the effect of nursing interventions on delirium of the patients admitted to ICU of the neurosurgery ward in Al-Zahra hospital in Isfahan. METHODS: A two-group multi-stage clinical trial study was carried out on 40 patients with hyperactive delirium admitted to ICU. The questionnaire included demographic data, Richmond Agitation Sedation Scale to assess the irritability rate and study method and also cognitive confusion in intensive care unit to determine delirium status of the study population. Simple sampling method was conducted and the study samples were randomly divided into two intervention and control groups. The following nursing interventions performed on the intervention group: assuring, emotional support, clear information and effective communication with the patients and their families and also allowing family visits twice a day. In the control group, the sample received the normal and routine ICU cares. The irritability and delirium severity status of the samples were analyzed on the day of admission and the fifth day using descriptive and inferential statistical methods and also SPSS software. RESULTS: Statistical analysis showed that although there was no significant difference between the groups on the first day of admission in terms of the irritability and delirium severity status, this was significant on the fifth day of the study. Wilcoxon test in the intervention and control groups indicated a significant difference between the study subjects in terms of the irritability and delirium severity status on the first day of admission and the fifth day which indicated the reduction in the irritability severity. But, this reduction was higher in the intervention group than in the control group. Furthermore, McNemar test showed that the number of the subjects with delirium in both groups reduced on the fifth day compared to the first day of admission and there was a significant difference between these two days, the number of samples without delirium in the intervention group was almost two times higher than that in the control group on the fifth day. CONCLUSIONS: Nursing interventions are considered as one of the non-pharmacological methods in treating delirium and by using these methods appropriately in ICUs, the patients' hypoactive delirium can be reduced. PMID- 22039388 TI - Effect of heat therapy on pain severity in primigravida women. AB - BACKGROUND: Labor pain relief has been considered since many years ago. Heat as a non pharmacological method of pain relief helps reducing the pain intensity and increases the pain consistency. The aim of the study was to determine the effect of the heat therapy on the labor pain in primigravida women. METHODS: In this clinical trial study, 64 low risk nulliparous women were randomly divided into two heat therapy and routine care groups. In addition to the routine cares, warm bag were used for the heat therapy group for the low back, from cervix dilatation of 3-4 cm to the end of the labor's first stage and for perinea at the second stage. The pain intensity was determined by McGill pain questionnaire in dilatation of 3-4, 6-7 and 9-10 cm and at the end of the labor's second stage. Data was analyzed using t-test and chi square test by using SPSS 11. RESULTS: Results of research showed a significant decrease in the pain intensity in the heat therapy group at the first stage and the second stage of labor and comparing two groups showed significant difference(p < 0.001). CONCLUSIONS: According to the results of this study, it seems that heat therapy in addition to its beneficial effects, causes the mother to sense the labor pain in a lower pain severity. PMID- 22039389 TI - Why differences exist? an interpretive approach to nurses' perceptions of cancer patients' quality of life. AB - BACKGROUND: Based on the literature review that was conducted, no research study has been found in Australia to provide a detailed understanding of why nurses differ in their perceptions about cancer patients' Quality of Life (QoL) when they communicate with patients in oncology wards. METHODS: This descriptive exploratory qualitative study was completed in 2007 in two major public hospitals in Adelaide, South Australia. 10 nurses from different inpatient and outpatient oncology services and a palliative setting took part in semi-structured interviews. RESULTS: After the data collection and analysis six main themes were identified. Differences in nurses' perceptions about cancer patients' QoL were discussed in the light of the sub theme "relationship and rapport". CONCLUSIONS: In general, participants commented that differences existing between patients' and nurses' perceptions about cancer patients' QoL were due to a poor relationship and rapport between cancer patients and their nurses. Therefore, nurses need to have a genuine interest to make an open relationship with patients in a non-judgmental way. This rapport needs to go beyond the patient and include other health care professionals as well as the patient's family. PMID- 22039390 TI - Spiritual care in hospitalized patients. AB - BACKGROUND: Spiritual needs are among an individual's essential needs in all places and times. With his physical and spiritual dimensions and the mutual effect of these two dimensions, human has spiritual needs as well. These needs are an intrinsic need throughout the life; therefore, they will remain as a major element of holistic nursing care. One of the greatest challenges for nurses is to satisfy the patients' spiritual needs. METHODS: This is a qualitative study with hermeneutic phenomenological approach. Data were collected from 16 patients hospitalized in internal medicine-surgery wards and 6 nurses in the respective wards. Data were generated by open-ended interview and analyzed using Diekelmann's seven-stage method. Rigorousness of findings was confirmed by use of this method as well as team interpretation, and referring to the text and participants. RESULTS: In final interpretation of the findings, totally 10 sub themes, three themes including formation of mutual relation with patient, encouraging the patient, and providing the necessary conditions for patient's connection with God, and one constitutive pattern, namely spiritual need of hospitalized patients. CONCLUSIONS: Spiritual needs are those needs whose satisfaction causes the person's spiritual growth and make the person a social, hopeful individual who always thanks God. They include the need for communication with others, communication with God, and being hopeful. In this study, the three obtained themes are the spiritual needs whose satisfaction is possible in nursing system. Considering these spiritual aspects accelerates patient's treatment. PMID- 22039391 TI - Reviewing the parental standpoint about origin of the dental fear in children referred to dentistry centers of Isfahan University of Medical Sciences. AB - BACKGROUND: Dental fear leads to lack of child cooperation. In general, without the patient's cooperation, success in remedy is impossible. This study aimed to evaluate parental view about the origins of the dental fear in children as well as their view about factors contributing to the prevention of child dental fear. METHODS: This was a cross sectional descriptive and analytical study which was carried out on 200 parents of children aged 6-12 years referred to dentistry center of Isfahan University of Medical Sciences. The level of dental fear in these children was screened using Children's Fear Survey Schedule - Dental Subscale (CFSS-DS). This questionnaire consisted of 15 questions and each question had a 5-point Likert-type Scale. Total scores ranged from 15 to 75. Based on the scores, children were divided into two groups: Group with low fear (score of 25 or less) and group with high fear (score of 37 or more). The parents were asked about the causes of their child's dental fear. RESULTS: There was an inverse significant correlation between the average score of fear and the age of the children. In the group with high fear, most of the parents (31%) had chosen previous dental experiences as the cause of their child's fear. There was no significant relationship between parental belief and their gender, the level of education, the level of their own dental fear and the child's age and fear score. CONCLUSIONS: According to the parent's standpoint, previous dental experience was a major factor in the development of childhood dental fear. Temperamental factors also played a major role in some of the fearful children. Most of the parents in group with high fear attributed their child's fear to the external factors and seemed they were unable to control and prevent it. Therefore, more attention should be given to the behavior and attitude of the parents as well as dentists in the future researches. PMID- 22039392 TI - Depletion forces drive polymer-like self-assembly in vibrofluidized granular materials. AB - Ranging from nano- to granular-scales, control of particle assembly can be achieved by limiting the available free space, for example by increasing the concentration of particles ("crowding") or through their restriction to 2D environments. It is unclear, however, if self-assembly principles governing thermally-equilibrated molecules can also apply to mechanically-excited macroscopic particles in non-equilibrium steady-state. Here we show that low densities of vibrofluidized steel rods, when crowded by high densities of spheres and confined to quasi-2D planes, can self-assemble into linear polymer-like structures. Our 2D Monte Carlo simulations show similar finite sized aggregates in thermally equilibrated binary mixtures. Using theory and simulations, we demonstrate how depletion interactions create oriented "binding" forces between rigid rods to form these "living polymers." Unlike rod-sphere mixtures in 3D that can demonstrate well-defined equilibrium phases, our mixtures confined to 2D lack these transitions because lower dimensionality favors the formation of linear aggregates, thus suppressing a true phase transition. The qualitative and quantitative agreement between equilibrium and granular patterning for these mixtures suggests that entropy maximization is the determining driving force for bundling. Furthermore, this study uncovers a previously unknown patterning behavior at both the granular and nanoscales, and may provide insights into the role of crowding at interfaces in molecular assembly. PMID- 22039393 TI - Deactivation of TEM-1 beta-Lactamase Investigated by Isothermal Batch and Non Isothermal Continuous Enzyme Membrane Reactor Methods. AB - The thermal deactivation of TEM-1 beta-lactamase was examined using two experimental techniques: a series of isothermal batch assays and a single, continuous, non-isothermal assay in an enzyme membrane reactor (EMR). The isothermal batch-mode technique was coupled with the three-state "Equilibrium Model" of enzyme deactivation, while the results of the EMR experiment were fitted to a four-state "molten globule model". The two methods both led to the conclusions that the thermal deactivation of TEM-1 beta-lactamase does not follow the Lumry-Eyring model and that the T(eq) of the enzyme (the point at which active and inactive states are present in equal amounts due to thermodynamic equilibrium) is at least 10 degrees C from the T(m) (melting temperature), contrary to the idea that the true temperature optimum of a biocatalyst is necessarily close to the melting temperature. PMID- 22039394 TI - Ampicillin Synthesis Using a Two-Enzyme Cascade with Both alpha-Amino Ester Hydrolase and Penicillin G Acylase. AB - The current enzymatic production of semisynthetic beta-lactam antibiotics requires isolation and purification of the intermediate 6-aminopenicillanic acid which adds cost and complexity to the manufacturing process. In this work, we took advantage of the unique substrate specificity of a-amino ester hydrolases to perform a purely aqueous one-pot production of ampicillin from penicillin G and D phenylglycine methyl ester, catalyzed by alpha-amino ester hydrolase and penicillin G acylase. The synthesis was performed in both a one-pot, one-step synthesis resulting in a maximum conversion of 39%, and a one-pot, two-step process resulting in a maximum conversion of 47%. The two-enzyme cascade reported in this paper is a promising alternative to the current enzymatic two-step, two pot manufacturing process for semisynthetic beta-lactam antibiotics which requires intermittent isolation of 6-aminopenicillanic acid. PMID- 22039395 TI - Relationship between Insulin Sensitivity and Muscle Lipids may Differ with Muscle Group and Ethnicity. AB - Intramyocellular lipid (IMCL) has been inversely associated with insulin sensitivity in some, but not all, studies. This study utilized fast, high resolution, magnetic resonance spectroscopic imaging (MRSI) to: investigate relationships between muscle lipids (IMCL and extramyocellular lipid (EMCL)) and insulin sensitivity in muscles of varying oxidative capacity, explore ethnic differences in these relationships, and determine whether a eucaloric, low-fat dietary intervention would reduce IMCL and increase insulin sensitivity. Subjects were 30 healthy, African-American (AA; n=14) and European-American (EA; n=16) males, BMI 26.49 (+/-5.57) kg/m(2), age 21.80 (+/-7.84) yrs. Soleus and tibialis anterior muscle lipids were quantified using MRSI. Insulin sensitivity was assessed via intravenous glucose tolerance test. A 2-week, eucaloric, low-fat diet intervention was conducted in a sub-group (n=12) subjects with assessments at baseline and post-intervention. Neither IMCL nor EMCL levels differed between ethnicities. In the total group, and within EA (but not AA), both tibialis anterior IMCL and EMCL were inversely associated with insulin sensitivity (P<0.05 for both); soleus muscle lipids were not associated with insulin sensitivity. Soleus, but not tibialis anterior, IMCL declined in both ethnic groups (average 25.3%; p<0.01) following dietary intervention; insulin sensitivity was unchanged. Results suggest that an association of muscle lipids with insulin sensitivity may be influenced by the oxidative capacity of the muscle group studied and may vary with ethnicity. PMID- 22039398 TI - A robust and rapid method of producing soluble, stable, and functional G-protein coupled receptors. AB - Membrane proteins, particularly G-protein coupled receptors (GPCRs), are notoriously difficult to express. Using commercial E. coli cell-free systems with the detergent Brij-35, we could rapidly produce milligram quantities of 13 unique GPCRs. Immunoaffinity purification yielded receptors at >90% purity. Secondary structure analysis using circular dichroism indicated that the purified receptors were properly folded. Microscale thermophoresis, a novel label-free and surface free detection technique that uses thermal gradients, showed that these receptors bound their ligands. The secondary structure and ligand-binding results from cell free produced proteins were comparable to those expressed and purified from HEK293 cells. Our study demonstrates that cell-free protein production using commercially available kits and optimal detergents is a robust technology that can be used to produce sufficient GPCRs for biochemical, structural, and functional analyses. This robust and simple method may further stimulate others to study the structure and function of membrane proteins. PMID- 22039399 TI - microRNA-150 regulates mobilization and migration of bone marrow-derived mononuclear cells by targeting Cxcr4. AB - The interaction between chemokine receptor type 4 (CXCR4) and its ligand, stromal cell-derived factor (SDF)-1, plays an important role in stem cell mobilization and migration in ischemic tissues. MicroRNAs (miRs) are key regulators of stem cell function and are involved in regulation of stem cell survival and differentiation to adopt different cell lineages. In this study, we show that ischemia inhibits the expression of miR-150 in BM-derived mononuclear cells (MNC) and activates its target Cxcr4 gene. Our results show that miR-150/CXCR4 cascade enhances MNC mobilization and migration. By using mouse acute myocardial infarction (MI) model, we found that MNCs in peripheral blood (PB) were increased significantly at day 5 after AMI as compared to control group and the number of CXCR4 positive MNCs both in bone marrow (BM) and PB was also markedly increased after MI. Analysis by microarray-based miRNA profiling and real-time PCR revealed that the expression of miR-150 which targets Cxcr4 gene as predicted was significantly downregulated in BM-MNCs after MI. Abrogation of miR-150 markedly increased CXCR4 protein expression suggesting its target gene. To show that miR 150 regulates MNC mobilization, knockdown of miR-150 in BM-MNCs by specific antisense inhibitor resulted in their higher migration ability in vitro as compared to scramble-transfected MNCs. Furthermore, in vivo BM transplantation of MNCs lacking miR-150 expression by lentiviral vector into the irradiated wild type mice resulted in the increased number of MNCs in PB after AMI as compared to control. In conclusion, this study demonstrates that ischemia mobilizes BM stem cells via miR-150/CXCR4 dependent mechanism and miR-150 may be a novel therapeutic target for stem cell migration to the ischemic tissue for neovascularization and repair. PMID- 22039400 TI - miRNA regulatory circuits in ES cells differentiation: a chemical kinetics modeling approach. AB - MicroRNAs (miRNAs) play an important role in gene regulation for Embryonic Stem cells (ES cells), where they either down-regulate target mRNA genes by degradation or repress protein expression of these mRNA genes by inhibiting translation. Well known tables TargetScan and miRanda may predict quite long lists of potential miRNAs inhibitors for each mRNA gene, and one of our goals was to strongly narrow down the list of mRNA targets potentially repressed by a known large list of 400 miRNAs. Our paper focuses on algorithmic analysis of ES cells microarray data to reliably detect repressive interactions between miRNAs and mRNAs. We model, by chemical kinetics equations, the interaction architectures implementing the two basic silencing processes of miRNAs, namely "direct degradation" or "translation inhibition" of targeted mRNAs. For each pair (M,G) of potentially interacting miRMA gene M and mRNA gene G, we parameterize our associated kinetic equations by optimizing their fit with microarray data. When this fit is high enough, we validate the pair (M,G) as a highly probable repressive interaction. This approach leads to the computation of a highly selective and drastically reduced list of repressive pairs (M,G) involved in ES cells differentiation. PMID- 22039401 TI - How accessible was information about H1N1 flu? Literacy assessments of CDC guidance documents for different audiences. AB - We assessed the literacy level and readability of online communications about H1N1/09 influenza issued by the Centers for Disease Control and Prevention (CDC) during the first month of outbreak. Documents were classified as targeting one of six audiences ranging in technical expertise. Flesch-Kincaid (FK) measure assessed literacy level for each group of documents. ANOVA models tested for differences in FK scores across target audiences and over time. Readability was assessed for documents targeting non-technical audiences using the Suitability Assessment of Materials (SAM). Overall, there was a main-effect by audience, F(5, 82) = 29.72, P<.001, but FK scores did not vary over time, F(2, 82) = .34, P>.05. A time-by-audience interaction was significant, F(10, 82) = 2.11, P<.05. Documents targeting non-technical audiences were found to be text-heavy and densely-formatted. The vocabulary and writing style were found to adequately reflect audience needs. The reading level of CDC guidance documents about H1N1/09 influenza varied appropriately according to the intended audience; sub-optimal formatting and layout may have rendered some text difficult to comprehend. PMID- 22039402 TI - Magnetic field is the dominant factor to induce the response of Streptomyces avermitilis in altered gravity simulated by diamagnetic levitation. AB - BACKGROUND: Diamagnetic levitation is a technique that uses a strong, spatially varying magnetic field to simulate an altered gravity environment, as in space. In this study, using Streptomyces avermitilis as the test organism, we investigate whether changes in magnetic field and altered gravity induce changes in morphology and secondary metabolism. We find that a strong magnetic field (12T) inhibit the morphological development of S. avermitilis in solid culture, and increase the production of secondary metabolites. METHODOLOGY/PRINCIPAL FINDINGS: S. avermitilis on solid medium was levitated at 0 g*, 1 g* and 2 g* in an altered gravity environment simulated by diamagnetic levitation and under a strong magnetic field, denoted by the asterix. The morphology was obtained by electromicroscopy. The production of the secondary metabolite, avermectin, was determined by OD(245 nm). The results showed that diamagnetic levitation could induce a physiological response in S. avermitilis. The difference between 1 g* and the control group grown without the strong magnetic field (1 g), showed that the magnetic field was a more dominant factor influencing changes in morphology and secondary metabolite production, than altered gravity. CONCLUSION/SIGNIFICANCE: We have discovered that magnetic field, rather than altered gravity, is the dominant factor in altered gravity simulated by diamagnetic levitation, therefore care should to be taken in the interpretation of results when using diamagnetic levitation as a technique to simulate altered gravity. Hence, these results are significant, and timely to researchers considering the use of diamagnetic levitation to explore effects of weightlessness on living organisms and on physical phenomena. PMID- 22039403 TI - Sabretoothed carnivores and the killing of large prey. AB - Sabre-like canines clearly have the potential to inflict grievous wounds leading to massive blood loss and rapid death. Hypotheses concerning sabretooth killing modes include attack to soft parts such as the belly or throat, where biting deep is essential to generate strikes reaching major blood vessels. Sabretoothed carnivorans are widely interpreted as hunters of larger and more powerful prey than that of their present-day nonsabretoothed relatives. However, the precise functional advantage of the sabretooth bite, particularly in relation to prey size, is unknown. Here, we present a new point-to-point bite model and show that, for sabretooths, depth of the killing bite decreases dramatically with increasing prey size. The extended gape of sabretooths only results in considerable increase in bite depth when biting into prey with a radius of less than ~10 cm. For sabretooths, this size-reversed functional advantage suggests predation on species within a similar size range to those attacked by present-day carnivorans, rather than "megaherbivores" as previously believed. The development of the sabretooth condition appears to represent a shift in function and killing behaviour, rather than one in predator-prey relations. Furthermore, our results demonstrate how sabretoothed carnivorans are likely to have evolved along a functionally continuous trajectory: beginning as an extension of a jaw-powered killing bite, as adopted by present-day pantherine cats, followed by neck-powered biting and thereafter shifting to neck-powered shear-biting. We anticipate this new insight to be a starting point for detailed study of the evolution of pathways that encompass extreme specialisation, for example, understanding how neck-powered biting shifts into shear-biting and its significance for predator prey interactions. We also expect that our model for point-to-point biting and bite depth estimations will yield new insights into the behaviours of a broad range of extinct predators including therocephalians (gorgonopsian + cynodont, sabretoothed mammal-like reptiles), sauropterygians (marine reptiles) and theropod dinosaurs. PMID- 22039404 TI - Mining virulence genes using metagenomics. AB - When a bacterial genome is compared to the metagenome of an environment it inhabits, most genes recruit at high sequence identity. In free-living bacteria (for instance marine bacteria compared against the ocean metagenome) certain genomic regions are totally absent in recruitment plots, representing therefore genes unique to individual bacterial isolates. We show that these Metagenomic Islands (MIs) are also visible in bacteria living in human hosts when their genomes are compared to sequences from the human microbiome, despite the compartmentalized structure of human-related environments such as the gut. From an applied point of view, MIs of human pathogens (e.g. those identified in enterohaemorragic Escherichia coli against the gut metagenome or in pathogenic Neisseria meningitidis against the oral metagenome) include virulence genes that appear to be absent in related strains or species present in the microbiome of healthy individuals. We propose that this strategy (i.e. recruitment analysis of pathogenic bacteria against the metagenome of healthy subjects) can be used to detect pathogenicity regions in species where the genes involved in virulence are poorly characterized. Using this approach, we detect well-known pathogenicity islands and identify new potential virulence genes in several human pathogens. PMID- 22039405 TI - SNPpy--database management for SNP data from genome wide association studies. AB - BACKGROUND: We describe SNPpy, a hybrid script database system using the Python SQLAlchemy library coupled with the PostgreSQL database to manage genotype data from Genome-Wide Association Studies (GWAS). This system makes it possible to merge study data with HapMap data and merge across studies for meta-analyses, including data filtering based on the values of phenotype and Single-Nucleotide Polymorphism (SNP) data. SNPpy and its dependencies are open source software. RESULTS: The current version of SNPpy offers utility functions to import genotype and annotation data from two commercial platforms. We use these to import data from two GWAS studies and the HapMap Project. We then export these individual datasets to standard data format files that can be imported into statistical software for downstream analyses. CONCLUSIONS: By leveraging the power of relational databases, SNPpy offers integrated management and manipulation of genotype and phenotype data from GWAS studies. The analysis of these studies requires merging across GWAS datasets as well as patient and marker selection. To this end, SNPpy enables the user to filter the data and output the results as standardized GWAS file formats. It does low level and flexible data validation, including validation of patient data. SNPpy is a practical and extensible solution for investigators who seek to deploy central management of their GWAS data. PMID- 22039406 TI - Conflict of interest in clinical practice guideline development: a systematic review. AB - BACKGROUND: There is an emerging literature on the existence and effect of industry relationships on physician and researcher behavior. Much less is known, however, about the effects of these relationships and other conflicts of interest (COI) on clinical practice guideline (CPG) development and recommendations. We performed a systematic review of the prevalence of COI and its effect on CPG recommendations. METHODOLOGY/PRINCIPAL FINDINGS: We searched Medline (1980 to March, 2011) for studies that examined the effect of COI on CPG development and/or recommendations. Data synthesis was qualitative. Twelve studies fulfilled inclusion criteria; 9 were conducted in the US. All studies reported on financial relationships of CPG authors with the pharmaceutical industry; 1 study also examined relationships with diagnostic testing and insurance companies. The majority of guidelines had authors with industry affiliations, including consultancies (authors with relationship, range 6-80%); research support (4-78%); equity/stock ownership (2-17%); or any COI (56-87%). Four studies reported multiple types of financial interactions for individual authors (number of types per author: range 2 to 10 or more). Data on the effect of COI on CPG recommendations were confined to case studies wherein authors with specific financial ties appeared to benefit from the related CPG recommendations. In a single study, few authors believed that their relationships influenced their recommendations. No studies reported on intellectual COI in CPGs. CONCLUSIONS/SIGNIFICANCE: There are limited data describing the high prevalence of COI among CPG authors, and only case studies of the effect of COI on CPG recommendations. Further research is needed to explore this potential source of bias. PMID- 22039407 TI - Can research assessments themselves cause bias in behaviour change trials? A systematic review of evidence from solomon 4-group studies. AB - BACKGROUND: The possible effects of research assessments on participant behaviour have attracted research interest, especially in studies with behavioural interventions and/or outcomes. Assessments may introduce bias in randomised controlled trials by altering receptivity to intervention in experimental groups and differentially impacting on the behaviour of control groups. In a Solomon 4 group design, participants are randomly allocated to one of four arms: (1) assessed experimental group; (2) unassessed experimental group (3) assessed control group; or (4) unassessed control group. This design provides a test of the internal validity of effect sizes obtained in conventional two-group trials by controlling for the effects of baseline assessment, and assessing interactions between the intervention and baseline assessment. The aim of this systematic review is to evaluate evidence from Solomon 4-group studies with behavioural outcomes that baseline research assessments themselves can introduce bias into trials. METHODOLOGY/PRINCIPAL FINDINGS: Electronic databases were searched, supplemented by citation searching. Studies were eligible if they reported appropriately analysed results in peer-reviewed journals and used Solomon 4-group designs in non-laboratory settings with behavioural outcome measures and sample sizes of 20 per group or greater. Ten studies from a range of applied areas were included. There was inconsistent evidence of main effects of assessment, sparse evidence of interactions with behavioural interventions, and a lack of convincing data in relation to the research question for this review. CONCLUSIONS/SIGNIFICANCE: There were too few high quality completed studies to infer conclusively that biases stemming from baseline research assessments do or do not exist. There is, therefore a need for new rigorous Solomon 4-group studies that are purposively designed to evaluate the potential for research assessments to cause bias in behaviour change trials. PMID- 22039408 TI - Proliferation of acid-secretory cells in the kidney during adaptive remodelling of the collecting duct. AB - The renal collecting duct adapts to changes in acid-base metabolism by remodelling and altering the relative number of acid or alkali secreting cells, a phenomenon termed plasticity. Acid secretory A intercalated cells (A-IC) express apical H(+)-ATPases and basolateral bicarbonate exchanger AE1 whereas bicarbonate secretory B intercalated cells (B-IC) express basolateral (and apical) H(+) ATPases and the apical bicarbonate exchanger pendrin. Intercalated cells were thought to be terminally differentiated and unable to proliferate. However, a recent report in mouse kidney suggested that intercalated cells may proliferate and that this process is in part dependent on GDF-15. Here we extend these observations to rat kidney and provide a detailed analysis of regional differences and demonstrate that differentiated A-IC proliferate massively during adaptation to systemic acidosis. We used markers of proliferation (PCNA, Ki67, BrdU incorporation) and cell-specific markers for A-IC (AE1) and B-IC (pendrin). Induction of remodelling in rats with metabolic acidosis (with NH(4)Cl for 12 hrs, 4 and 7 days) or treatment with acetazolamide for 10 days resulted in a larger fraction of AE1 positive cells in the cortical collecting duct. A large number of AE1 expressing A-IC was labelled with proliferative markers in the cortical and outer medullary collecting duct whereas no labeling was found in B IC. In addition, chronic acidosis also increased the rate of proliferation of principal collecting duct cells. The fact that both NH(4)Cl as well as acetazolamide stimulated proliferation suggests that systemic but not urinary pH triggers this response. Thus, during chronic acidosis proliferation of AE1 containing acid-secretory cells occurs and may contribute to the remodelling of the collecting duct or replace A-IC due to a shortened life span under these conditions. PMID- 22039409 TI - Perinatal flavour learning and adaptation to being weaned: all the pig needs is smell. AB - Perinatal flavour learning through the maternal diet is known to enhance flavour preference and acceptance of flavoured food in many species, yet still little is known about the mechanism underlying perinatal flavour learning. Previously we found positive effects of perinatal flavour learning on food intake, growth and behaviour of piglets postweaning, but no increased preference for the flavour. This suggests that flavour learning in pigs works through a reduction of weaning stress by the presence of the familiar flavour instead. The aim of this study was to investigate whether perinatal flavour learning reduces stress at weaning, and whether the effect is stronger when the familiar flavour is present in the food. Sows were offered an anethol-flavoured diet (Flavour treatment) or control diet (Control treatment) during late gestation and lactation. Flavour and Control piglets were provided with anethol either in their food (Food treatment) or in the air (Air treatment) after weaning. Preweaning and postweaning treatments did not affect food intake, preference or growth in the first two weeks postweaning but flavour treatment reduced the latency to eat (24 versus 35 hours, P = 0.02) and within-pen variation in growth (SD within-pen: 0.7 versus 1.2 kg, P<0.001). Salivary cortisol levels tended to be lower four and seven hours postweaning for Flavour piglets compared to Control piglets (4 hours: 2.5 versus 3.0 ng/ml, P = 0.05, 7 hours: 3.1 versus 3.4 ng/ml, P = 0.08). Flavour piglets played more and showed less damaging behaviours than Control piglets, indicating that the familiar flavour reduced stress around weaning. Few interaction effects were found between preweaning and postweaning treatment, and no effects of postweaning treatment. We conclude that in the newly weaned pig, perinatal flavour learning results in a reduction of stress when the familiar flavour is present, regardless of providing the flavour in the food or in the air. PMID- 22039410 TI - Lack of an association of PD-1 and its ligand genes with Behcet's disease in a Chinese Han population. AB - BACKGROUND: Behcet's disease is a chronic, multi-systemic autoimmune disease. Programmed cell death 1 (PD-1) gene is one of non-human leucocyte antigen genes. It has been demonstrated to be associated with several autoimmune diseases. However, only a few studies have addressed the association of ligand genes of PD 1, PD-L1 and PD-L2 with autoimmune disease. The purpose of this study was to analyze the potential association of the PD-1 and its ligand genes with Behcet's disease in a Chinese Han population. METHODOLOGY/PRINCIPAL FINDINGS: Four single nucleotide polymorphism (SNPs) rs2227981 and rs10204525 of PD-1, rs1970000 of PD L1 and rs7854303 of PD-L2 were genotyped in 405 Behcet's patients and 414 age-, sex-, ethnic-matched healthy controls using polymerase chain reaction-restriction fragment length polymorphism assay. The results revealed that there were no significant differences in the genotype and allele frequencies of PD-1 rs2227981 and rs10204525 between the Behcet's patients and controls. A similar result was found for PD-L1 rs1970000 versus healthy controls. Only the C allele and the CC genotype of PD-L2 rs7854303 were identified in patients and controls. Stratification analysis based on gender and clinical findings did not show any associations between PD-1 or its ligand polymorphisms and Behcet's disease. CONCLUSIONS/SIGNIFICANCE: None of the currently studied SNPs, PD-1 rs2227981 and rs10204525, PD-L1 rs1970000 and PD-L2 rs7854303, are associated with the susceptibility to Behcet's disease in a Chinese Han population. More studies are needed to confirm these findings in Behcet's patients with other ethnic backgrounds. PMID- 22039411 TI - Areca users in combination with tobacco and alcohol use are associated with younger age of diagnosed esophageal cancer in Taiwanese men. AB - BACKGROUND: Whether the habitual use of substances (tobacco, alcohol, or areca nut (seed of the Areca palm)) can affect the age of esophageal squamous cell carcinoma (ESCC) presentation has rarely been examined. METHODS: The study subjects were those who were males and the first time to be diagnosed as ESCC (ICD-9 150) and who visited any of three medical centers in Taiwan between 2000 and 2009. A standardized questionnaire was used to collect substance uses and other variables. RESULTS: Mean age (+/-SD) at presentation of ESCC was 59.2 (+/ 11.3) years in a total of 668 cases. After adjusting for other covariates, alcohol drinkers were 3.58 years younger to have ESCC than non-drinkers (p = 0.002). A similar result was found among areca chewers, who were 6.34 years younger to have ESCC than non-chewers (p<0.0001), but not among cigarette smokers (p = 0.10). When compared to the group using 0-1 substances, subjects using both cigarettes and alcohol were nearly 3 years younger to contract ESCC. Furthermore, those who use areca plus another substance were 7-8 years younger. Subjects using all three substances had the greatest age difference, 9.20 years younger (p<0.0001), compared to the comparison group. CONCLUSION: Our findings suggest that habitually consuming tobacco, alcohol, and areca nut can influence the age onset of ESCC. Since the development of ESCC is insidious and life-threatening, our observation is worthy to be reconfirmed in the large-scale and long-term follow-up prospective cohort studies to recommend the screening strategy of this disease. PMID- 22039412 TI - Direct ex-vivo evaluation of pneumococcal specific T-cells in healthy adults. AB - Streptococcus pneumoniae is an encapsulated bacterium that causes significant global morbidity and mortality. The nasopharynxes of children are believed to be the natural reservoir of pneumococcus and by adulthood nasopharyngeal carriage is infrequent; such infrequency may be due to demonstrable pneumococcal specific T and B-cell responses. HLA Class 2 tetrameric complexes have been used to characterise antigen specific T-cell responses in a variety of models of infection. We therefore sought to determine the frequency and phenotype of pneumococcal specific T-cells, using a novel HLA-DRB1*1501 tetramer complex incorporating a recently defined T-cell epitope derived from the conserved pneumococcal serine/threonine kinase (StkP). We were able to detect direct ex vivo StkP(446-60)-tetramer binding in HLA-DRB1*1501 adults. These StkP(446-60) tetramer binding T-cells had increased CD38 expression and were enriched in CCR7- CD45RA+ expression indicating recent and on-going activation and differentiation. Furthermore, these StkP(446-60)-tetramer binding T-cells demonstrated rapid effector function by secreting interferon-gamma on stimulation with recombinant StkP. This is the first study to directly enumerate and characterise pneumococcal specific T-cells using HLA class 2 tetrameric complexes. We found that ex-vivo pneumococcal-specific T cells were detectable in healthy adults and that they were enriched with cell surface markers associated with recent antigen exposure and later stages of antigen-driven differentiation. It is likely that these activated pneumococcal specific T-cells reflect recent immunostimulatory pneumococcal exposure in the nasopharynx and it is possible that they may be preventing subsequent colonisation and disease. PMID- 22039414 TI - Geographically widespread swordfish barcode stock identification: a case study of its application. AB - BACKGROUND: The swordfish (Xiphias gladius) is a cosmopolitan large pelagic fish inhabiting tempered and tropical waters and it is a target species for fisheries all around the world. The present study investigated the ability of COI barcoding to reliably identify swordfish and particularly specific stocks of this commercially important species. METHODOLOGY: We applied the classical DNA barcoding technology, upon a 682 bp segment of COI, and compared swordfish sequences from different geographical sources (Atlantic, Indian Oceans and Mediterranean Sea). The sequences of the 5' hyper-variable fragment of the control region (5'dloop), were also used to validate the efficacy of COI as a stock-specific marker. CASE REPORT: This information was successfully applied to the discrimination of unknown samples from the market, detecting in some cases mislabeled seafood products. CONCLUSIONS: The NJ distance-based phenogram (K2P model) obtained with COI sequences allowed us to correlate the swordfish haplotypes to the different geographical stocks. Similar results were obtained with 5'dloop. Our preliminary data in swordfish Xiphias gladius confirm that Cytochrome Oxidase I can be proposed as an efficient species-specific marker that has also the potential to assign geographical provenance. This information might speed the samples analysis in commercial application of barcoding. PMID- 22039413 TI - A cross-sectional study of HPV vaccine acceptability in Gaborone, Botswana. AB - BACKGROUND: Cervical cancer is the most common cancer among women in Botswana and elsewhere in Sub-Saharan Africa. We sought to examine whether HPV vaccine is acceptable among parents in Botswana, which recently licensed the vaccine to prevent cervical cancer. METHODS AND FINDINGS: We conducted a cross-sectional survey in 2009, around the time the vaccine was first licensed, with adults recruited in general medicine and HIV clinics in Gaborone, the capital of Botswana. Although only 9% (32/376) of respondents had heard of HPV vaccine prior to the survey, 88% (329/376) said they definitely will have their adolescent daughters receive HPV vaccine. Most respondents would get the vaccine for their daughters at a public or community clinic (42%) or a gynecology or obstetrician's office (39%), and 74% would get it for a daughter if it were available at her school. Respondents were more likely to say that they definitely will get HPV vaccine for their daughters if they had less education (OR = 0.20, 95% CI = 0.07 0.58) or lived more than 30 kilometers from the capital, Gaborone (OR = 2.29, 95% CI = 1.06-4.93). Other correlates of acceptability were expecting to be involved in the decision to get HPV vaccine, thinking the vaccine would be hard to obtain, and perceiving greater severity of HPV-related diseases. CONCLUSIONS: HPV vaccination of adolescent girls would be highly acceptable if the vaccine became widely available to the daughters of healthcare seeking parents in Gaborone, Botswana. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine as well as work to minimize barriers. PMID- 22039415 TI - Disgust sensitivity and the neurophysiology of left-right political orientations. AB - Disgust has been described as the most primitive and central of emotions. Thus, it is not surprising that it shapes behaviors in a variety of organisms and in a variety of contexts--including homo sapien politics. People who believe they would be bothered by a range of hypothetical disgusting situations display an increased likelihood of displaying right-of-center rather than left-of-center political orientations. Given its primal nature and essential value in avoiding pathogens disgust likely has an effect even without registering in conscious beliefs. In this article, we demonstrate that individuals with marked involuntary physiological responses to disgusting images, such as of a man eating a large mouthful of writhing worms, are more likely to self-identify as conservative and, especially, to oppose gay marriage than are individuals with more muted physiological responses to the same images. This relationship holds even when controlling for the degree to which respondents believe themselves to be disgust sensitive and suggests that people's physiological predispositions help to shape their political orientations. PMID- 22039416 TI - Network fluctuations hinder cooperation in evolutionary games. AB - In this paper we study the influence of random network fluctuations on the behavior of evolutionary games on Barabasi-Albert networks. This network class has been shown to promote cooperation on social dilemmas such as the Prisoner's Dilemma and the Snowdrift games when the population network is fixed. Here we introduce exogenous random fluctuations of the network links through several noise models, and we investigate the evolutionary dynamics comparing them with the known static network case. The results we obtain show that even a moderate amount of random noise on the network links causes a significant loss of cooperation, to the point that cooperation vanishes altogether in the Prisoner's Dilemma when the noise rate is the same as the agents' strategy revision rate. The results appear to be robust since they are essentially the same whatever the type of the exogenous noise. Besides, it turns out that random network noise is more important than strategy noise in suppressing cooperation. Thus, even in the more favorable situation of accumulated payoff in which links have no cost, the mere presence of random external network fluctuations act as a powerful limitation to the attainment of high levels of cooperation. PMID- 22039417 TI - Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer. AB - FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10) human hepatocellular carcinoma, 66.7% (6/9) liver cancer cell lines and 100% (6/6) colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2'-deoxycytidine (Aza), indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS) generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis. PMID- 22039418 TI - Event-related potential correlates of performance-monitoring in a lateralized time-estimation task. AB - Performance-monitoring as a key function of cognitive control covers a wide range of diverse processes to enable goal directed behavior and to avoid maladjustments. Several event-related brain potentials (ERP) are associated with performance-monitoring, but their conceptual background differs. For example, the feedback-related negativity (FRN) is associated with unexpected performance feedback and might serve as a teaching signal for adaptational processes, whereas the error-related negativity (ERN) is associated with error commission and subsequent behavioral adaptation. The N2 is visible in the EEG when the participant successfully inhibits a response following a cue and thereby adapts to a given stop-signal. Here, we present an innovative paradigm to concurrently study these different performance-monitoring-related ERPs. In 24 participants a tactile time-estimation task interspersed with infrequent stop-signal trials reliably elicited all three ERPs. Sensory input and motor output were completely lateralized, in order to estimate any hemispheric processing preferences for the different aspects of performance monitoring associated with these ERPs. In accordance with the literature our data suggest augmented inhibitory capabilities in the right hemisphere given that stop-trial performance was significantly better with left- as compared to right-hand stop-signals. In line with this, the N2 scalp distribution was generally shifted to the right in addition to an ipsilateral shift in relation to the response hand. Other than that, task lateralization affected neither behavior related to error and feedback processing nor ERN or FRN. Comparing the ERP topographies using the Global Map Dissimilarity index, a large topographic overlap was found between all considered components.With an evenly distributed set of trials and a split-half reliability for all ERP components >=.85 the task is well suited to efficiently study N2, ERN, and FRN concurrently which might prove useful for group comparisons, especially in clinical populations. PMID- 22039419 TI - Development of non-natural flavanones as antimicrobial agents. AB - With growing concerns over multidrug resistance microorganisms, particularly strains of bacteria and fungi, evolving to become resistant to the antimicrobial agents used against them, the identification of new molecular targets becomes paramount for novel treatment options. Recently, the use of new treatments containing multiple active ingredients has been shown to increase the effectiveness of existing molecules for some infections, often with these added compounds enabling the transport of a toxic molecule into the infecting species. Flavonoids are among the most abundant plant secondary metabolites and have been shown to have natural abilities as microbial deterrents and anti-infection agents in plants. Combining these ideas we first sought to investigate the potency of natural flavonoids in the presence of efflux pump inhibitors to limit Escherichia coli growth. Then we used the natural flavonoid scaffold to synthesize non natural flavanone molecules and further evaluate their antimicrobial efficacy on Escherichia coli, Bacillus subtilis and the fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus. Of those screened, we identified the synthetic molecule 4-chloro-flavanone as the most potent antimicrobial compound with a MIC value of 70 ug/mL in E. coli when combined with the inhibitor Phe-Arg beta-naphthylamide, and MICs of 30 ug/mL in S. cerevesiae and 30 ug/mL in C. neoformans when used alone. Through this study we have demonstrated that combinatorial synthesis of non-natural flavonones can identify novel antimicrobial agents with activity against bacteria and fungi but with minimal toxicity to human cells. PMID- 22039420 TI - Hypervirulent Clostridium difficile PCR-ribotypes exhibit resistance to widely used disinfectants. AB - The increased prevalence of Clostridium difficile infection (CDI) has coincided with enhanced transmissibility and severity of disease, which is often linked to two distinct clonal lineages designated PCR-ribotype 027 and 017 responsible for CDI outbreaks in the USA, Europe and Asia. We assessed sporulation and susceptibility of three PCR-ribotypes; 012, 017 and 027 to four classes of disinfectants; chlorine releasing agents (CRAs), peroxygens, quaternary ammonium compounds (QAC) and biguanides. The 017 PCR-ribotype, showed the highest sporulation frequency under these test conditions. The oxidizing biocides and CRAs were the most efficacious in decontamination of C. difficile vegetative cells and spores, the efficacy of the CRAs were concentration dependent irrespective of PCR-ribotype. However, there were differences observed in the susceptibility of the PCR-ribotypes, independent of the concentrations tested for Virkon(r), Newgenn(r), Proceine 40(r) and Hibiscrub(r). Whereas, for Steri7(r) and Biocleanse(r) the difference observed between the disinfectants were dependent on both PCR-ribotype and concentration. The oxidizing agent Perasafe(r) was consistently efficacious across all three PCR ribotypes at varying concentrations; with a consistent five Log10 reduction in spore titre. The PCR ribotype and concentration dependent differences in the efficacy of the disinfectants in this study indicate that disinfectant choice is a factor for llimiting the survival and transmission of C. difficile spores in healthcare settings. PMID- 22039421 TI - Alternative transcript initiation and splicing as a response to DNA damage. AB - Humans are exposed to the DNA damaging agent, ionizing radiation (IR), from background radiation, medical treatments, occupational and accidental exposures. IR causes changes in transcription, but little is known about alternative transcription in response to IR on a genome-wide basis. These investigations examine the response to IR at the exon level in human cells, using exon arrays to comprehensively characterize radiation-induced transcriptional expression products. Previously uncharacterized alternative transcripts that preferentially occur following IR exposure have been discovered. A large number of genes showed alternative transcription initiation as a response to IR. Dose-response and time course kinetics have also been characterized. Interestingly, most genes showing alternative transcript induction maintained these isoforms over the dose range and times tested. Finally, clusters of co-ordinately up- and down-regulated radiation response genes were identified at specific chromosomal loci. These data provide the first genome-wide view of the transcriptional response to ionizing radiation at the exon level. This study provides novel insights into alternative transcripts as a mechanism for response to DNA damage and cell stress responses in general. PMID- 22039422 TI - Biodiversity offsets: a cost-effective interim solution to seabird bycatch in fisheries? AB - The concept of biodiversity offsets is well established as an approach to environmental management. The concept has been suggested for environmental management in fisheries, particularly in relation to the substantial numbers of non-target species--seabirds in particular--caught and killed as incidental bycatch during fishing activities. Substantial areas of fisheries are being closed to protect these species at great cost to the fishing industry. However, other actions may be taken to offset the impact of fishing on these populations at lower cost to the fishing industry. This idea, however, has attracted severe criticism largely as it does not address the underlying externality problems created by the fishing sector, namely seabird fishing mortality. In this paper, we re-examine the potential role of compensatory mitigation as a fisheries management tool, although from the perspective of being an interim management measure while more long-lasting solutions to the problem are found. We re-model an example previously examined by both proponents and opponents of the approach, namely the cost effectiveness of rodent control relative to fishery area closures for the conservation of a seabird population adversely affected by an Australian tuna fishery. We find that, in the example being examined, invasive rodent eradication is at least 10 times more cost effective than area closures. We conclude that, while this does not solve the actual bycatch problem, it may provide breathing space for both the seabird species and the industry to find longer term means of reducing bycatch. PMID- 22039423 TI - Inner speech during silent reading reflects the reader's regional accent. AB - While reading silently, we often have the subjective experience of inner speech. However, there is currently little evidence regarding whether this inner voice resembles our own voice while we are speaking out loud. To investigate this issue, we compared reading behaviour of Northern and Southern English participants who have differing pronunciations for words like 'glass', in which the vowel duration is short in a Northern accent and long in a Southern accent. Participants' eye movements were monitored while they silently read limericks in which the end words of the first two lines (e.g., glass/class) would be pronounced differently by Northern and Southern participants. The final word of the limerick (e.g., mass/sparse) then either did or did not rhyme, depending on the reader's accent. Results showed disruption to eye movement behaviour when the final word did not rhyme, determined by the reader's accent, suggesting that inner speech resembles our own voice. PMID- 22039424 TI - H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination. AB - BACKGROUND: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection. METHODS AND FINDINGS: To study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject. CONCLUSION: The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains. PMID- 22039425 TI - BRAF mutations in advanced cancers: clinical characteristics and outcomes. AB - BACKGROUND: Oncogenic BRAF mutations have been found in diverse malignancies and activate RAF/MEK/ERK signaling, a critical pathway of tumorigenesis. We examined the clinical characteristics and outcomes of patients with mutant (mut) BRAF advanced cancer referred to phase 1 clinic. METHODS: We reviewed the records of 80 consecutive patients with mutBRAF advanced malignancies and 149 with wild-type (wt) BRAF (matched by tumor type) referred to the Clinical Center for Targeted Therapy and analyzed their outcome. RESULTS: Of 80 patients with mutBRAF advanced cancer, 56 had melanoma, 10 colorectal, 11 papillary thyroid, 2 ovarian and 1 esophageal cancer. Mutations in codon 600 were found in 77 patients (62, V600E; 13, V600K; 1, V600R; 1, unreported). Multivariate analysis showed less soft tissue (Odds ratio (OR) = 0.39, 95%CI: 0.20-0.77, P = 0.007), lung (OR = 0.38, 95%CI: 0.19-0.73, p = 0.004) and retroperitoneal metastases (OR = 0.34, 95%CI: 0.13-0.86, p = 0.024) and more brain metastases (OR = 2.05, 95%CI: 1.02-4.11, P = 0.043) in patients with mutBRAF versus wtBRAF. Comparing to the corresponding wtBRAF, mutBRAF melanoma patients had insignificant trend to longer median survival from diagnosis (131 vs. 78 months, p = 0.14), while mutBRAF colorectal cancer patients had an insignificant trend to shorter median survival from diagnosis (48 vs. 53 months, p = 0.22). In melanoma, V600K mutations in comparison to other BRAF mutations were associated with more frequent brain (75% vs. 36.3%, p = 0.02) and lung metastases (91.6% vs. 47.7%, p = 0.007), and shorter time from diagnosis to metastasis and to death (19 vs. 53 months, p = 0.046 and 78 vs. 322 months, p = 0.024 respectively). Treatment with RAF/MEK targeting agents (Hazard ratio (HR) = 0.16, 95%CI: 0.03-0.89, p = 0.037) and any decrease in tumor size after referral (HR = 0.07, 95%CI: 0.015-0.35, p = 0.001) correlated with longer survival in mutBRAF patients. CONCLUSIONS: BRAF appears to be a druggable mutation that also defines subgroups of patients with phenotypic overlap, albeit with differences that correlate with histology or site of mutation. PMID- 22039426 TI - Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein. AB - Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS), but no nuclear export signal (NES) has yet been identified.We show here that the aa(109-133) region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126) in the identified NES or in the sequence encoding the mature core aa(1 173) significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication.Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection. PMID- 22039427 TI - Genomic analyses, gene expression and antigenic profile of the trans-sialidase superfamily of Trypanosoma cruzi reveal an undetected level of complexity. AB - The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a highly debilitating human pathology that affects millions of people in the Americas. The sequencing of this parasite's genome reveals that trans sialidase/trans-sialidase-like (TcS), a polymorphic protein family known to be involved in several aspects of T. cruzi biology, is the largest T. cruzi gene family, encoding more than 1,400 genes. Despite the fact that four TcS groups are well characterized and only one of the groups contains active trans-sialidases, all members of the family are annotated in the T. cruzi genome database as trans sialidase. After performing sequence clustering analysis with all TcS complete genes, we identified four additional groups, demonstrating that the TcS family is even more heterogeneous than previously thought. Interestingly, members of distinct TcS groups show distinctive patterns of chromosome localization. Members of the TcSgroupII, which harbor proteins involved in host cell attachment/invasion, are preferentially located in subtelomeric regions, whereas members of the largest and new TcSgroupV have internal chromosomal locations. Real-time RT-PCR confirms the expression of genes derived from new groups and shows that the pattern of expression is not similar within and between groups. We also performed B-cell epitope prediction on the family and constructed a TcS specific peptide array, which was screened with sera from T. cruzi-infected mice. We demonstrated that all seven groups represented in the array are antigenic. A highly reactive peptide occurs in sixty TcS proteins including members of two new groups and may contribute to the known cross-reactivity of T. cruzi epitopes during infection. Taken together, our results contribute to a better understanding of the real complexity of the TcS family and open new avenues for investigating novel roles of this family during T. cruzi infection. PMID- 22039428 TI - Abnormal parietal function in conversion paresis. AB - The etiology of medically unexplained symptoms such as conversion disorder is poorly understood. This is partly because the interpretation of neuroimaging results in conversion paresis has been complicated by the use of different control groups, tasks and statistical comparisons. The present study includes these different aspects in a single data set. In our study we included both normal controls and feigners to control for conversion paresis. We studied both movement execution and imagery, and we contrasted both within-group and between group activation. Moreover, to reveal hemisphere-specific effects that have not been reported before, we performed these analyses using both flipped and unflipped data. This approach resulted in the identification of abnormal parietal activation which was specific for conversion paresis patients. Patients also showed reduced activity in the prefrontal cortex, supramarginal gyrus and precuneus, including hemisphere-specific activation that is lateralized in the same hemisphere, regardless of right- or left-sided paresis. We propose that these regions are candidates for an interface between psychological mechanisms and disturbed higher-order motor control. Our study presents an integrative neurophysiological view of the mechanisms that contribute to the etiology of this puzzling psychological disorder, which can be further investigated with other types of conversion symptoms. PMID- 22039429 TI - Estimated glomerular filtration rate and the risk of major vascular events and all-cause mortality: a meta-analysis. AB - BACKGROUND: Lower estimated glomerular filtration rate (eGFR) has been associated with an increased risk of major vascular events (MVEs) and death, but differences in methodology make between-study comparisons difficult. We used a novel method to summarise the published results. METHODS AND FINDINGS: Studies assessing the relationship between baseline eGFR and subsequent MVEs or all cause mortality were identified using Pubmed. Those which involved at least 500 individuals, planned at least 1 year of follow-up, reported age and sex adjusted relative risks, and provided the mean eGFR in each category (or sufficient information to allow its estimation) were included. To take account of differences in underlying risk between studies, proportional within-study differences in eGFR (rather than absolute eGFR values) were related to risk. Fifty studies (2 million participants) assessing MVEs and 67 studies (5 million participants) assessing all cause mortality were eligible. There was an inverse relationship between lower eGFR and the risk of MVEs and of death. In studies among people without prior vascular disease, a 30% lower eGFR level was on average associated with a 29% (SE 0.2%) increase in the risk of a MVE and a 31% (SE 0.2%) increase in the risk of death from any cause. In studies among people with prior vascular disease, these estimates were 26% (SE 1.0%) and 23% (SE 0.2%) respectively. While there was substantial statistical heterogeneity between the results of individual studies, a 30% lower eGFR was consistently associated with a 20-30% higher risk of both outcomes, irrespective of prior history of vascular disease or study design. CONCLUSIONS: Lower eGFR was consistently associated with a moderate increase in the risk of death and MVEs. If these relationships are causal and continuous, then around one fifth of vascular events among those over 70 years might be attributable to renal impairment. PMID- 22039430 TI - A multi-compartment, single and multiple dose pharmacokinetic study of the vaginal candidate microbicide 1% tenofovir gel. AB - BACKGROUND: Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. METHODS AND FINDINGS: Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median C(max) was 4.0 and 3.4 ng/mL, respectively (C<=29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2*10(4) to 9.9*10(6) ng/mL and 2.1*10(2) to 1.4*10(6) ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1*10(3) to 8.8*10(6) ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8*10(2) to 3.5*10(4) ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. CONCLUSIONS: Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00561496. PMID- 22039431 TI - Molecular basis of Bcl-X(L)-p53 interaction: insights from molecular dynamics simulations. AB - Bcl-X(L), an antiapoptotic Bcl-2 family protein, plays a central role in the regulation of the apoptotic pathway. Heterodimerization of the antiapoptotic Bcl 2 family proteins with the proapoptotic family members such as Bad, Bak, Bim and Bid is a crucial step in the apoptotic regulation. In addition to these conventional binding partners, recent evidences reveal that the Bcl-2 family proteins also interact with noncanonical binding partners such as p53. Our previous NMR studies showed that Bcl-X(L): BH3 peptide and Bcl-X(L): SN15 peptide (a peptide derived from residues S15-N29 of p53) complex structures share similar modes of bindings. To further elucidate the molecular basis of the interactions, here we have employed molecular dynamics simulations coupled with MM/PBSA approach. Bcl-X(L) and other Bcl-2 family proteins have 4 hydrophobic pockets (p1 p4), which are occupied by four systematically spaced hydrophobic residues (h1 h4) of the proapoptotic Bad and Bak BH3 peptides. We observed that three conserved hydrophobic residues (F19, W23 and L26) of p53 (SN15) peptide anchor into three hydrophobic pockets (p2-p4) of Bcl-X(L) in a similar manner as BH3 peptide. Our results provide insights into the novel molecular recognition by Bcl X(L) with p53. PMID- 22039432 TI - Excision of an unstable pathogenicity island in Salmonella enterica serovar Enteritidis is induced during infection of phagocytic cells. AB - The availability of the complete genome sequence of several Salmonella enterica serovars has revealed the presence of unstable genetic elements in these bacteria, such as pathogenicity islands and prophages. This is the case of Salmonella enterica serovar Enteritidis (S. Enteritidis), a bacterium that causes gastroenteritis in humans and systemic infection in mice. The whole genome sequence analysis for S. Enteritidis unveiled the presence of several genetic regions that are absent in other Salmonella serovars. These regions have been denominated "regions of difference" (ROD). In this study we show that ROD21, one of such regions, behaves as an unstable pathogenicity island. We observed that ROD21 undergoes spontaneous excision by two independent recombination events, either under laboratory growth conditions or during infection of murine cells. Importantly, we also found that one type of excision occurred at higher rates when S. Enteritidis was residing inside murine phagocytic cells. These data suggest that ROD21 is an unstable pathogenicity island, whose frequency of excision depends on the environmental conditions found inside phagocytic cells. PMID- 22039433 TI - Rapid high yield production of different glycoforms of Ebola virus monoclonal antibody. AB - BACKGROUND: Fc-glycosylation of monoclonal antibodies (mAbs) has profound implications on the Fc-mediated effector functions. Alteration of this glycosylation may affect the efficiency of an antibody. However, difficulties in the production of mAbs with homogeneous N-glycosylation profiles in sufficient amounts hamper investigations of the potential biological impact of different glycan residues. METHODOLOGY/PRINCIPAL FINDINGS: Here we set out to evaluate a transient plant viral based production system for the rapid generation of different glycoforms of a monoclonal antibody. Ebola virus mAb h-13F6 was generated using magnICON expression system in Nicotiana benthamiana, a plant species developed for commercial scale production of therapeutic proteins. h-13F6 was co-expressed with a series of modified mammalian enzymes involved in the processing of complex N-glycans. Using wild type (WT) plants and the glycosylation mutant DeltaXTFT that synthesizes human like biantennary N-glycans with terminal N-acetylglucosamine on each branch (GnGn structures) as expression hosts we demonstrate the generation of h-13F6 complex N-glycans with (i) bisected structures, (ii) core alpha1,6 fucosylation and (iii) beta1,4 galactosylated oligosaccharides. In addition we emphasize the significance of precise sub Golgi localization of enzymes for engineering of IgG Fc-glycosylation. CONCLUSION: The method described here allows the efficient generation of a series of different human-like glycoforms at large homogeneity of virtually any antibody within one week after cDNA delivery to plants. This accelerates follow up functional studies and thus may contribute to study the biological role of N-glycan residues on Fcs and maximizing the clinical efficacy of therapeutic antibodies. PMID- 22039434 TI - FilmArray, an automated nested multiplex PCR system for multi-pathogen detection: development and application to respiratory tract infection. AB - The ideal clinical diagnostic system should deliver rapid, sensitive, specific and reproducible results while minimizing the requirements for specialized laboratory facilities and skilled technicians. We describe an integrated diagnostic platform, the "FilmArray", which fully automates the detection and identification of multiple organisms from a single sample in about one hour. An unprocessed biologic/clinical sample is subjected to nucleic acid purification, reverse transcription, a high-order nested multiplex polymerase chain reaction and amplicon melt curve analysis. Biochemical reactions are enclosed in a disposable pouch, minimizing the PCR contamination risk. FilmArray has the potential to detect greater than 100 different nucleic acid targets at one time. These features make the system well-suited for molecular detection of infectious agents. Validation of the FilmArray technology was achieved through development of a panel of assays capable of identifying 21 common viral and bacterial respiratory pathogens. Initial testing of the system using both cultured organisms and clinical nasal aspirates obtained from children demonstrated an analytical and clinical sensitivity and specificity comparable to existing diagnostic platforms. We demonstrate that automated identification of pathogens from their corresponding target amplicon(s) can be accomplished by analysis of the DNA melting curve of the amplicon. PMID- 22039436 TI - Use of recombinant adenovirus vectored consensus IFN-alpha to avert severe arenavirus infection. AB - Several arenaviruses can cause viral hemorrhagic fever, a severe disease with case-fatality rates in hospitalized individuals ranging from 15-30%. Because of limited prophylaxis and treatment options, new medical countermeasures are needed for these viruses classified by the National Institutes of Allergy and Infectious Diseases (NIAID) as top priority biodefense Category A pathogens. Recombinant consensus interferon alpha (cIFN-alpha) is a licensed protein with broad clinical appeal. However, while cIFN-alpha has great therapeutic value, its utility for biodefense applications is hindered by its short in vivo half-life, mode and frequency of administration, and costly production. To address these limitations, we describe the use of DEF201, a replication-deficient adenovirus vector that drives the expression of cIFN-alpha, for pre- and post-exposure prophylaxis of acute arenaviral infection modeled in hamsters. Intranasal administration of DEF201 24 h prior to challenge with Pichinde virus (PICV) was highly effective at protecting animals from mortality and preventing viral replication and liver associated disease. A significant protective effect was still observed with a single dosing of DEF201 given two weeks prior to PICV challenge. DEF201 was also efficacious when administered as a treatment 24 to 48 h post-virus exposure. The protective effect of DEF201 was largely attributed to the expression of cIFN alpha, as dosing with a control empty vector adenovirus did not protect hamsters from lethal PICV challenge. Effective countermeasures that are highly stable, easily administered, and elicit long lasting protective immunity are much needed for arena and other viral infections. The DEF201 technology has the potential to address all of these issues and may serve as a broad-spectrum antiviral to enhance host defense against a number of viral pathogens. PMID- 22039435 TI - Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation. AB - The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP), global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs). We further document that a Myc core signature (MCS) set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in EMU-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells. PMID- 22039437 TI - Warfarin anticoagulation exacerbates the risk of hemorrhagic transformation after rt-PA treatment in experimental stroke: therapeutic potential of PCC. AB - BACKGROUND: Oral anticoagulant therapy (OAT) with warfarin is the standard of stroke prevention in patients with atrial fibrillation. Approximately 30% of patients with cardioembolic strokes are on OAT at the time of symptom onset. We investigated whether warfarin exacerbates the risk of thrombolysis-associated hemorrhagic transformation (HT) in a mouse model of ischemic stroke. METHODS: 62 C57BL/6 mice were used for this study. To achieve effective anticoagulation, warfarin was administered orally. We performed right middle cerebral artery occlusion (MCAO) for 3 h and assessed functional deficit and HT blood volume after 24 h. RESULTS: In non-anticoagulated mice, treatment with rt-PA (10 mg/kg i.v.) after 3 h MCAO led to a 5-fold higher degree of HT compared to vehicle treated controls (4.0+/-0.5 ul vs. 0.8+/-0.1, p<0.001). Mice on warfarin revealed larger amounts of HT after rt-PA treatment in comparison to non-anticoagulated mice (9.2+/-3.2 ul vs. 2.8+/-1.0, p<0.05). The rapid reversal of anticoagulation by means of prothrombin complex concentrates (PCC, 100 IU/kg) at the end of the 3 h MCAO period, but prior to rt-PA administration, neutralized the exacerbated risk of HT as compared to sham-treated controls (3.8+/-0.7 ul vs. 15.0+/-3.8, p<0.001). CONCLUSION: In view of the vastly increased risk of HT, it seems to be justified to withhold tPA therapy in effectively anticoagulated patients with acute ischemic stroke. The rapid reversal of anticoagulation with PCC prior to tPA application reduces the risk attributed to warfarin pretreatment and may constitute an interesting therapeutic option. PMID- 22039438 TI - On the implications of a sex difference in the reaction times of sprinters at the Beijing Olympics. AB - Elite sprinters offer insights into the fastest whole body auditory reaction times. When, however, is a reaction so fast that it represents a false start? Currently, a false start is awarded if an athlete increases the force on their starting block above a given threshold before 100 ms has elapsed after the starting gun. To test the hypothesis that the fastest valid reaction times of sprinters really is 100 ms and that no sex difference exists in that time, we analyzed the fastest reaction times achieved by each of the 425 male and female sprinters who competed at the 2008 Beijing Olympics. After power transformation of the skewed data, a fixed effects ANOVA was used to analyze the effects of sex, race, round and lane position. The lower bounds of the 95, 99 and 99.9% confidence intervals were then calculated and back transformed. The mean fastest reaction time recorded by men was significantly faster than women (p<0.001). At the 99.9% confidence level, neither men nor women can react in 100 ms, but they can react in as little as 109 ms and 121 ms, respectively. However, that sex difference in reaction time is likely an artifact caused by using the same force threshold in women as men, and it permits a woman to false start by up to 21 ms without penalty. We estimate that female sprinters would have similar reaction times to male sprinters if the force threshold used at Beijing was lowered by 22% in order to account for their lesser muscle strength. PMID- 22039439 TI - Galectin-3 and Beclin1/Atg6 genes in human cancers: using cDNA tissue panel, qRT PCR, and logistic regression model to identify cancer cell biomarkers. AB - BACKGROUND: Cancer biomarkers are sought to support cancer diagnosis, predict cancer patient response to treatment and survival. Identifying reliable biomarkers for predicting cancer treatment response needs understanding of all aspects of cancer cell death and survival. Galectin-3 and Beclin1 are involved in two coordinated pathways of programmed cell death, apoptosis and autophagy and are linked to necroptosis/necrosis. The aim of the study was to quantify galectin 3 and Beclin1 mRNA in human cancer tissue cDNA panels and determine their utility as biomarkers of cancer cell survival. METHODS AND RESULTS: A panel of 96 cDNAs from eight (8) different normal and cancer tissue types were used for quantitative real-time polymerase chain reaction (qRT-PCR) using ABI7900HT. Miner2.0, a web-based 4- and 3-parameter logistic regression software was used to derive individual well polymerase chain reaction efficiencies (E) and cycle threshold (Ct) values. Miner software derived formula was used to calculate mRNA levels and then fold changes. The ratios of cancer to normal tissue levels of galectin-3 and Beclin1 were calculated (using the mean for each tissue type). Relative mRNA expressions for galectin-3 were higher than for Beclin1 in all tissue (normal and cancer) types. In cancer tissues, breast, kidney, thyroid and prostate had the highest galectin-3 mRNA levels compared to normal tissues. High levels of Beclin1 mRNA levels were in liver and prostate cancers when compared to normal tissues. Breast, kidney and thyroid cancers had high galectin-3 levels and low Beclin1 levels. CONCLUSION: Galectin-3 expression patterns in normal and cancer tissues support its reported roles in human cancer. Beclin1 expression pattern supports its roles in cancer cell survival and in treatment response. qRT PCR analysis method used may enable high throughput studies to generate molecular biomarker sets for diagnosis and predicting cancer treatment response. PMID- 22039440 TI - Cysteamine attenuates the decreases in TrkB protein levels and the anxiety/depression-like behaviors in mice induced by corticosterone treatment. AB - OBJECTIVE: Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders. MATERIALS AND METHODS: We examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure. RESULTS: Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine. CONCLUSIONS: The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders. PMID- 22039441 TI - Nasal chemosensory-stimulation evoked activity patterns in the rat trigeminal ganglion visualized by in vivo voltage-sensitive dye imaging. AB - Mammalian nasal chemosensation is predominantly mediated by two independent neuronal pathways, the olfactory and the trigeminal system. Within the early olfactory system, spatiotemporal responses of the olfactory bulb to various odorants have been mapped in great detail. In contrast, far less is known about the representation of volatile chemical stimuli at an early stage in the trigeminal system, the trigeminal ganglion (TG), which contains neurons directly projecting to the nasal cavity. We have established an in vivo preparation that allows high-resolution imaging of neuronal population activity from a large region of the rat TG using voltage-sensitive dyes (VSDs). Application of different chemical stimuli to the nasal cavity elicited distinct, stimulus category specific, spatiotemporal activation patterns that comprised activated as well as suppressed areas. Thus, our results provide the first direct insights into the spatial representation of nasal chemosensory information within the trigeminal ganglion imaged at high temporal resolution. PMID- 22039442 TI - Comprehensive evaluation of one-carbon metabolism pathway gene variants and renal cell cancer risk. AB - INTRODUCTION: Folate and one-carbon metabolism are linked to cancer risk through their integral role in DNA synthesis and methylation. Variation in one-carbon metabolism genes, particularly MTHFR, has been associated with risk of a number of cancers in epidemiologic studies, but little is known regarding renal cancer. METHODS: Tag single nucleotide polymorphisms (SNPs) selected to produce high genomic coverage of 13 gene regions of one-carbon metabolism (ALDH1L1, BHMT, CBS, FOLR1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, TYMS) and the closely associated glutathione synthesis pathway (CTH, GGH, GSS) were genotyped for 777 renal cell carcinoma (RCC) cases and 1,035 controls in the Central and Eastern European Renal Cancer case-control study. Associations of individual SNPs (n = 163) with RCC risk were calculated using unconditional logistic regression adjusted for age, sex and study center. Minimum p-value permutation (Min-P) tests were used to identify gene regions associated with risk, and haplotypes were evaluated within these genes. RESULTS: The strongest associations with RCC risk were observed for SLC19A1 (P(min-P) = 0.03) and MTHFR (P(min-P) = 0.13). A haplotype consisting of four SNPs in SLC19A1 (rs12483553, rs2838950, rs2838951, and rs17004785) was associated with a 37% increased risk (p = 0.02), and exploratory stratified analysis suggested the association was only significant among those in the lowest tertile of vegetable intake. CONCLUSIONS: To our knowledge, this is the first study to comprehensively examine variation in one-carbon metabolism genes in relation to RCC risk. We identified a novel association with SLC19A1, which is important for transport of folate into cells. Replication in other populations is required to confirm these findings. PMID- 22039443 TI - IL-27 imparts immunoregulatory function to human NK cell subsets. AB - Interleukin-27 (IL-27) is a cytokine with multiple roles in regulating the immune response, but its effect on human CD56(bright) and CD56(dim) NK cell subsets is unknown. NK cell subsets interact with other components of the immune system, leading to cytotoxicity or immunoregulation depending on stimulating factors. We found that IL-27 treatment results in increased IL-10 and IFN-gamma expression, increased viability and decreased proliferation in both CD56(bright) and CD56(dim) NK cell subsets. More importantly, IL-27 treatment imparts regulatory activity to CD56(bright) NK cells, which mediates its suppressive function on T cells in a contact-dependent manner. There is growing evidence that CD56(bright) NK cell-mediated immunoregulation plays an important role in the control of autoimmunity. Thus, understanding the role of IL-27 in NK cell function has important implications for treatment of autoimmune disorders. PMID- 22039444 TI - OmniChange: the sequence independent method for simultaneous site-saturation of five codons. AB - Focused mutant library generation methods have been developed to improve mainly "localizable" enzyme properties such as activity and selectivity. Current multi site saturation methods are restricted by the gene sequence, require subsequent PCR steps and/or additional enzymatic modifications. Here we report, a multiple site saturation mutagenesis method, OmniChange, which simultaneously and efficiently saturates five independent codons. As proof of principle, five chemically cleaved DNA fragments, each carrying one NNK-degenerated codon, were generated and assembled to full gene length in a one-pot-reaction without additional PCR-amplification or use of restriction enzymes or ligases. Sequencing revealed the presence of up to 27 different codons at individual positions, corresponding to 84.4% of the theoretical diversity offered by NNK-degeneration. OmniChange is absolutely sequence independent, does not require a minimal distance between mutated codons and can be accomplished within a day. PMID- 22039445 TI - High-fat diet with acyl-ghrelin treatment leads to weight gain with low inflammation, high oxidative capacity and normal triglycerides in rat muscle. AB - Obesity is associated with muscle lipid accumulation. Experimental models suggest that inflammatory cytokines, low mitochondrial oxidative capacity and paradoxically high insulin signaling activation favor this alteration. The gastric orexigenic hormone acylated ghrelin (A-Ghr) has antiinflammatory effects in vitro and it lowers muscle triglycerides while modulating mitochondrial oxidative capacity in lean rodents. We tested the hypothesis that A-Ghr treatment in high-fat feeding results in a model of weight gain characterized by low muscle inflammation and triglycerides with high muscle mitochondrial oxidative capacity. A-Ghr at a non-orexigenic dose (HFG: twice-daily 200-ug s.c.) or saline (HF) were administered for 4 days to rats fed a high-fat diet for one month. Compared to lean control (C) HF had higher body weight and plasma free fatty acids (FFA), and HFG partially prevented FFA elevation (P<0.05). HFG also had the lowest muscle inflammation (nuclear NFkB, tissue TNF-alpha) with mitochondrial enzyme activities higher than C (P<0.05 vs C, P = NS vs HF). Under these conditions HFG prevented the HF-associated muscle triglyceride accumulation (P<0.05). The above effects were independent of changes in redox state (total-oxidized glutathione, glutathione peroxidase activity) and were not associated with changes in phosphorylation of AKT and selected AKT targets. Ghrelin administration following high-fat feeding results in a novel model of weight gain with low inflammation, high mitochondrial enzyme activities and normalized triglycerides in skeletal muscle. These effects are independent of changes in tissue redox state and insulin signaling, and they suggest a potential positive metabolic impact of ghrelin in fat-induced obesity. PMID- 22039446 TI - Occurrence of grapevine leafroll-associated virus complex in Napa Valley. AB - Grapevine leafroll disease (GLD) is caused by a complex of several virus species (grapevine leafroll-associated viruses, GLRaV) in the family Closteroviridae. Because of its increasing importance, it is critical to determine which species of GLRaV is predominant in each region where this disease is occurring. A structured sampling design, utilizing a combination of RT-PCR based testing and sequencing methods, was used to survey GLRaVs in Napa Valley (California, USA) vineyards (n = 36). Of the 216 samples tested for GLRaV-1, -2, -3, -4, -5, and 9, 62% (n = 134) were GLRaV positive. Of the positives, 81% (n = 109) were single infections with GLRaV-3, followed by GLRaV-2 (4%, n = 5), while the remaining samples (15%, n = 20) were mixed infections of GLRaV-3 with GLRaV-1, 2, 4, or 9. Additionally, 468 samples were tested for genetic variants of GLRaV-3, and of the 65% (n = 306) of samples positive for GLRaV-3, 22% were infected with multiple GLRaV-3 variants. Phylogenetic analysis utilizing sequence data from the single infection GLRaV-3 samples produced seven well-supported GLRaV-3 variants, of which three represented 71% of all GLRaV-3 positive samples in Napa Valley. Furthermore, two novel variants, which grouped with a divergent isolate from New Zealand (NZ-1), were identified, and these variants comprised 6% of all positive GLRaV-3 samples. Spatial analyses showed that GLRaV-3a, 3b, and 3c were not homogeneously distributed across Napa Valley. Overall, 86% of all blocks (n = 31) were positive for GLRaVs and 90% of positive blocks (n = 28) had two or more GLRaV-3 variants, suggesting complex disease dynamics that might include multiple insect-mediated introduction events. PMID- 22039447 TI - Deep sequencing of pyrethroid-resistant bed bugs reveals multiple mechanisms of resistance within a single population. AB - A frightening resurgence of bed bug infestations has occurred over the last 10 years in the U.S. and current chemical methods have been inadequate for controlling this pest due to widespread insecticide resistance. Little is known about the mechanisms of resistance present in U.S. bed bug populations, making it extremely difficult to develop intelligent strategies for their control. We have identified bed bugs collected in Richmond, VA which exhibit both kdr-type (L925I) and metabolic resistance to pyrethroid insecticides. Using LD(50) bioassays, we determined that resistance ratios for Richmond strain bed bugs were ~5200-fold to the insecticide deltamethrin. To identify metabolic genes potentially involved in the detoxification of pyrethroids, we performed deep-sequencing of the adult bed bug transcriptome, obtaining more than 2.5 million reads on the 454 titanium platform. Following assembly, analysis of newly identified gene transcripts in both Harlan (susceptible) and Richmond (resistant) bed bugs revealed several candidate cytochrome P450 and carboxylesterase genes which were significantly over-expressed in the resistant strain, consistent with the idea of increased metabolic resistance. These data will accelerate efforts to understand the biochemical basis for insecticide resistance in bed bugs, and provide molecular markers to assist in the surveillance of metabolic resistance. PMID- 22039448 TI - Contributions of the MyD88-dependent receptors IL-18R, IL-1R, and TLR9 to host defenses following pulmonary challenge with Cryptococcus neoformans. AB - Signaling via the adapter protein, MyD88, is important in the host defense against Cryptococcus neoformans infection. While certain Toll-like receptors (TLRs) can enhance the clearance of Cryptococcus, the contributions of MyD88 dependent, TLR-independent pathways have not been fully investigated. We examined the roles of IL-1R and IL-18R in vivo by challenging C57BL/6 mice with a lethal strain of Cryptococcus. We found that the absence of IL-18R, but not IL-1R, causes a shift in the survival curve following pulmonary delivery of a virulent strain of C. neoformans (H99). Specifically, IL-18R-deficient mice have significantly shorter median survival times compared to wild-type mice following infection. Cytokine analysis of lung homogenates revealed that deficiency of IL IR, IL-18R, or MyD88 is associated with diminished lung levels of IL-1beta. In order to compare these findings with those related to TLR-deficiency, we studied the effects of TLR9-deficiency and found that deficiency of TLR9 also affects the survival curve of mice following challenge with C. neoformans. Yet the lungs from infected TLR9-deficient mice have robust levels of IL-1beta. In summary, we found that multiple signaling components can contribute the MyD88-dependent host responses to cryptococcal infection in vivo and each drives distinct pulmonary responses. PMID- 22039449 TI - Molecular analysis of virulent determinants of enterovirus 71. AB - Enterovirus 71 (EV71) is the most important causative agent of hand, foot and mouth disease (HFMD) in children. In most cases, it is a self-limiting illness. However some EV71 infectious cases can develop severe clinical outcomes, such as encephalitis, meningitis, poliomyelitis like paralysis, and even death. To identify the determinants of virulence, the deduced amino acid sequence of polyprotein and nucleotide sequence of 5'-NTR and 3'-NTR in 25 SC-EV71 strains (strains from severe cases) and 31 MC-EV71 strains (strains from mild cases) were analyzed. Results showed four amino acids on two positions (Gly(P710)/Gln(P710)/Arg(P710) and Glu(P729)) on the DE and EF loop of VP1, one (Lys(P930)) on the surface of protease 2A and four nucleotides on three positions (G(P272), U(P488) and A(P700)/U(P700)) in the 5'-NTR region are associated with EV71 virulent phenotype. Predicted secondary structure of RNA using the consensus sequence of 5'-NTR by RNAStructure showed the mutation of nucleotide at position 488 in strain BJ08-Z004-3 (position 491 in prototype strain BrCr) can result in the discrepancy of an additional pair of nucleotides and thus change the stability of the second structure of IRES. Fragment base content analysis showed that in the region 696 to 714 bp at the 5'-NTR, where the A(P700)/U(P700) was located, the nucleotide constitution ratios differed significantly between SC EV71 and MC-EV71 strains. In conclusion, comparative genomic analysis showed that virulence of EV71 strains are mainly determined by the amino acids on two positions of VP1, one position of protease 2A and the nucleotides on three positions in 5'-NTR. PMID- 22039450 TI - Molecular characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and impact of T-cell epitope mutations on HLA recognition (ANRS 12159). AB - BACKGROUND: To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding. METHODS: We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores) and HLA binding (MHC score). RESULTS: All sequences clustered with CRF01_AE. HLA class I genotyping showed the predominance of Asian alleles as A*11:01 and B*46:01 with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (+/-0.9) versus 2 (+/-0.7) in non-divergent ones (p<0.0001). CONCLUSIONS: Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area. PMID- 22039451 TI - Functional ramifications for the loss of P-selectin expression on hematopoietic and leukemic stem cells. AB - Hematopoiesis is a tightly regulated biological process that relies upon complicated interactions between blood cells and their microenvironment to preserve the homeostatic balance of long-term hematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs), multipotent progenitors (MPPs), and differentiated cells. Adhesion molecules like P-selectin (encoded by the Selp gene) are essential to hematopoiesis, and their dysregulation has been linked to leukemogenesis. Like HSCs, leukemic stem cells (LSCs) depend upon their microenvironments for survival and propagation. P-selectin plays a crucial role in Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML). In this paper, we show that cells deficient in P-selectin expression can repopulate the marrow more efficiently than wild type controls. This results from an increase in HSC self-renewal rather than alternative possibilities like increased homing velocity or cell cycle defects. We also show that P-selectin expression on LT-HSCs, but not ST-HSCs and MPPs, increases with aging. In the absence of P selectin expression, mice at 6 months of age possess increased levels of short term HSCs and multipotent progenitors. By 11 months of age, there is a shift towards increased levels of long-term HSCs. Recipients of BCR-ABL-transduced bone marrow cells from P-selectin-deficient donors develop a more aggressive CML, with increased percentages of LSCs and progenitors. Taken together, our data reveal that P-selectin expression on HSCs and LSCs has important functional ramifications for both hematopoiesis and leukemogenesis, which is most likely attributable to an intrinsic effect on stem cell self-renewal. PMID- 22039452 TI - Quercetin inhibits IL-1beta-induced inflammation, hyaluronan production and adipogenesis in orbital fibroblasts from Graves' orbitopathy. AB - Management of Graves' orbitopathy (GO) is challenging, as no reliable, specific, and safe medical therapeutic agents have yet been developed. We investigated the effect of quercetin in primary cultured orbital fibroblasts from GO, targeting pathways of inflammation, aberrant accumulation of extracellular matrix macromolecules, and adipose tissue expansion. Quercetin significantly attenuated intercellular adhesion molecule-1 (ICAM-1), interleukin (IL) -6, IL-8, and cyclooxygenase (COX) -2 mRNA expression, and inhibited IL-1beta-induced increases in ICAM-1, IL-6, and IL-8 mRNA. Increased hyaluronan production induced by IL 1beta or tumor necrosis factor-alpha was suppressed by quercetin in a dose- and time-dependent manner. Treatment with noncytotoxic doses of quercetin inhibited accumulation of intracytoplasmic lipid droplets and resulted in a dose-dependent decrease in expression of peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein (C/EBP) alpha, and C/EBPbeta proteins. In conclusion, inhibition of inflammation, hyaluronan production, and adipogenesis by the natural plant product quercetin in vitro provides the basis for further study of its potential use in the treatment of GO. PMID- 22039453 TI - Ulcerogenic Helicobacter pylori strains isolated from children: a contribution to get insight into the virulence of the bacteria. AB - Infection with Helicobacter pylori is the major cause for the development of peptic ulcer disease (PUD). In children, with no other etiology for the disease, this rare event occurs shortly after infection. In these young patients, habits of smoking, diet, consumption of alcohol and non-steroid anti-inflammatory drugs and stress, in addition to the genetic susceptibility of the patient, represent a minor influence. Accordingly, the virulence of the implicated H. pylori strain should play a crucial role in the development of PUD. Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins. To uncover virulence features, we compared the proteome of these two groups of H. pylori strains. Two-dimensional gel electrophoresis followed by mass-spectrometry allowed us to detect 27 differentially expressed proteins between them. In addition to the presence of genes encoding well established virulence factors, namely cagA, vacAs1, oipA "on" status, homB and jhp562 genes, the pediatric ulcerogenic strains shared a proteome profile characterized by changes in the abundance of: motility associated proteins, accounting for higher motility; antioxidant proteins, which may confer increased resistance to inflammation; and enzymes involved in key steps in the metabolism of glucose, amino acids and urea, which may be advantageous to face fluctuations of nutrients. In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors. PMID- 22039454 TI - Effect of acute Plasmodium falciparum malaria on reactivation and shedding of the eight human herpes viruses. AB - Human herpes viruses (HHVs) are widely distributed pathogens. In immuno-competent individuals their clinical outcomes are generally benign but in immuno compromised hosts, primary infection or extensive viral reactivation can lead to critical diseases. Plasmodium falciparum malaria profoundly affects the host immune system. In this retrospective study, we evaluated the direct effect of acute P. falciparum infection on reactivation and shedding of all known human herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8). We monitored their presence by real time PCR in plasma and saliva of Ugandan children with malaria at the day of admission to the hospital (day-0) and 14 days later (after treatment), or in children with mild infections unrelated to malaria. For each child screened in this study, at least one type of HHV was detected in the saliva. HHV-7 and HHV-6 were detected in more than 70% of the samples and CMV in approximately half. HSV-1, HSV-2, VZV and HHV-8 were detected at lower frequency. During salivary shedding the highest mean viral load was observed for HSV-1 followed by EBV, HHV-7, HHV-6, CMV and HHV-8. After anti-malarial treatment the salivary HSV-1 levels were profoundly diminished or totally cleared. Similarly, four children with malaria had high levels of circulating EBV at day-0, levels that were cleared after anti-malarial treatment confirming the association between P. falciparum infection and EBV reactivation. This study shows that acute P. falciparum infection can contribute to EBV reactivation in the blood and HSV-1 reactivation in the oral cavity. Taken together our results call for further studies investigating the potential clinical implications of HHVs reactivation in children suffering from malaria. PMID- 22039455 TI - RMRP is a non-coding RNA essential for early murine development. AB - RMRP is a non-coding RNA that is ubiquitously expressed in both humans and mice. RMRP mutations that lead to decreased RMRP levels are found in the pleiotropic syndrome Cartilage Hair Hypoplasia. To assess the effects of deleting RMRP, we engineered a targeting vector that contains loxP sequences flanking RMRP and created hemizygous mice harboring this engineered allele (RMRP conditional). We found that insertion of this cassette suppressed RMRP expression, and we failed to obtain viable mice homozygous for the RMRP conditional allele. Furthermore, we were unable to obtain viable homozygous RMRP null mice, indicating that RMRP is essential for early embryonic development. PMID- 22039456 TI - Excess risk of maternal death from sickle cell disease in Jamaica: 1998-2007. AB - BACKGROUND: Decreases in direct maternal deaths in Jamaica have been negated by growing indirect deaths. With sickle cell disease (SCD) a consistent underlying cause, we describe the epidemiology of maternal deaths in this population. METHODS: Demographic, service delivery and cause specific mortality rates were compared among women with (n = 42) and without SCD (n = 376), and between SCD women who died in 1998-2002 and 2003-7. RESULTS: Women with SCD had fewer viable pregnancies (p: 0.02) despite greater access to high risk antenatal care (p: 0.001), and more often died in an intensive care unit (p: 0.002). In the most recent period (2003-7) SCD women achieved more pregnancies (median 2 vs. 3; p: 0.009), made more antenatal visits (mean 3.3 vs. 7.3; p: 0.01) and were more often admitted antenatally (p:<0.0001). The maternal mortality ratio for SCD decedents was 7-11 times higher than the general population, with 41% of deaths attributable to their disorder. Cause specific mortality was higher for cardiovascular complications, gestational hypertension and haemorrhage. Respiratory failure was the leading immediate cause of death. CONCLUSIONS: Women with SCD experience a significant excess risk of dying in pregnancy and childbirth [MMR: (SCD) 719/100,000, (non SCD) 78/100,000]. MDG5 cannot be realised without improving care for women with SCD. Tertiary services (e.g. ventilator support) are needed at regional centres to improve outcomes in this and other high risk populations. Universal SCD screening in pregnancy in populations of African and Mediterranean descent is needed as are guidelines for managing SCD pregnancies and educating families with SCD. PMID- 22039457 TI - Modulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex. AB - The outcome of many infections depends on the initial interactions between agent and host. Aiming at elucidating the effect of the M. tuberculosis Mce1 protein complex on host transcriptional and immunological responses to infection with M. tuberculosis, RNA from murine macrophages at 15, 30, 60 min, 4 and 10 hrs post infection with M. tuberculosis H37Rv or Delta-mce1 H37Rv was analyzed by whole genome microarrays and RT-QPCR. Immunological responses were measured using a 23 plex cytokine assay. Compared to uninfected controls, 524 versus 64 genes were up regulated by 15 min post H37Rv- and Delta-mce1 H37Rv-infection, respectively. By 15 min post-H37Rv infection, a decline of 17 cytokines combined with up regulation of Ccl24 (26.5-fold), Clec4a2 (23.2-fold) and Ppargamma (10.5-fold) indicated an anti-inflammatory response initiated by IL-13. Down-regulation of Il13ra1 combined with up-regulation of Il12b (30.2-fold), suggested switch to a pro-inflammatory response by 4 hrs post H37Rv-infection. Whereas no significant change in cytokine concentration or transcription was observed during the first hour post Delta-mce1 H37Rv-infection, a significant decline of IL-1b, IL-9, IL 13, Eotaxin and GM-CSF combined with increased transcription of Il12b (25.1-fold) and Inb1 (17.9-fold) by 4 hrs, indicated a pro-inflammatory response. The balance between pro-and anti-inflammatory responses during the early stages of infection may have significant bearing on outcome. PMID- 22039458 TI - Determinants of functional coupling between astrocytes and respiratory neurons in the pre-Botzinger complex. AB - Respiratory neuronal network activity is thought to require efficient functioning of astrocytes. Here, we analyzed neuron-astrocyte communication in the pre Botzinger Complex (preBotC) of rhythmic slice preparations from neonatal mice. In astrocytes that exhibited rhythmic potassium fluxes and glutamate transporter currents, we did not find a translation of respiratory neuronal activity into phase-locked astroglial calcium signals. In up to 20% of astrocytes, 2-photon calcium imaging revealed spontaneous calcium fluctuations, although with no correlation to neuronal activity. Calcium signals could be elicited in preBotC astrocytes by metabotropic glutamate receptor activation or after inhibition of glial glutamate uptake. In the latter case, astrocyte calcium elevation preceded a surge of respiratory neuron discharge activity followed by network failure. We conclude that astrocytes do not exhibit respiratory-rhythmic calcium fluctuations when they are able to prevent synaptic glutamate accumulation. Calcium signaling is, however, observed when glutamate transport processes in astrocytes are suppressed or neuronal discharge activity is excessive. PMID- 22039459 TI - Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies. AB - Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis. PMID- 22039460 TI - ConDeTri--a content dependent read trimmer for Illumina data. AB - During the last few years, DNA and RNA sequencing have started to play an increasingly important role in biological and medical applications, especially due to the greater amount of sequencing data yielded from the new sequencing machines and the enormous decrease in sequencing costs. Particularly, Illumina/Solexa sequencing has had an increasing impact on gathering data from model and non-model organisms. However, accurate and easy to use tools for quality filtering have not yet been established. We present ConDeTri, a method for content dependent read trimming for next generation sequencing data using quality scores of each individual base. The main focus of the method is to remove sequencing errors from reads so that sequencing reads can be standardized. Another aspect of the method is to incorporate read trimming in next-generation sequencing data processing and analysis pipelines. It can process single-end and paired-end sequence data of arbitrary length and it is independent from sequencing coverage and user interaction. ConDeTri is able to trim and remove reads with low quality scores to save computational time and memory usage during de novo assemblies. Low coverage or large genome sequencing projects will especially gain from trimming reads. The method can easily be incorporated into preprocessing and analysis pipelines for Illumina data. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://code.google.com/p/condetri. PMID- 22039461 TI - Mechanism of disruption of the Amt-GlnK complex by P(II)-mediated sensing of 2 oxoglutarate. AB - GlnK proteins regulate the active uptake of ammonium by Amt transport proteins by inserting their regulatory T-loops into the transport channels of the Amt trimer and physically blocking substrate passage. They sense the cellular nitrogen status through 2-oxoglutarate, and the energy level of the cell by binding both ATP and ADP with different affinities. The hyperthermophilic euryarchaeon Archaeoglobus fulgidus possesses three Amt proteins, each encoded in an operon with a GlnK ortholog. One of these proteins, GlnK2 was recently found to be incapable of binding 2-OG, and in order to understand the implications of this finding we conducted a detailed structural and functional analysis of a second GlnK protein from A. fulgidus, GlnK3. Contrary to Af-GlnK2 this protein was able to bind both ATP/2-OG and ADP to yield inactive and functional states, respectively. Due to the thermostable nature of the protein we could observe the exact positioning of the notoriously flexible T-loops and explain the binding behavior of GlnK proteins to their interaction partner, the Amt proteins. A thermodynamic analysis of these binding events using microcalorimetry evaluated by microstate modeling revealed significant differences in binding cooperativity compared to other characterized P(II) proteins, underlining the diversity and adaptability of this class of regulatory signaling proteins. PMID- 22039462 TI - Recognition and avoidance of contaminated flowers by foraging bumblebees (Bombus terrestris). AB - Bumblebee colonies are founded by a single-mated queen. Due to this life history trait, bumblebees are more susceptible to parasites and diseases than polyandrous and/or polygynous social insects. A greater resistance towards parasites is shown when the genetic variability within a colony is increased. The parasite resistance may be divided into different levels regarding the step of the parasite infection (e.g. parasite uptake, parasite intake, parasite's establishment in the nest, parasite transmission). We investigate the prophylactic behaviour of bumblebees. Bumblebees were observed during their foraging flights on two artificial flowers; one of these was contaminated by Crithidia bombi, a naturally occurring gut parasite of bumblebees (in a control experiment the non-specific pathogen Escherichia coli was used). For C. bombi, bumblebees were preferentially observed feeding on the non-contaminated flower. Whereas for E. coli, the number of visits between flowers was the same, bumblebees spent more time feeding on the non-contaminated flower. These results demonstrate the ability of bumblebees to recognise the contamination of food sources. In addition, bumblebees have a stronger preference for the non contaminated flower when C. bombi is present in the other flower than with E. coli which might be explained as an adaptive behaviour of bumblebees towards this specific gut parasite. It seems that the more specific the parasite is, the more it reduces the reward of the flower. PMID- 22039463 TI - A component of retinal light adaptation mediated by the thyroid hormone cascade. AB - Analysis with DNA-microrrays and real time PCR show that several genes involved in the thyroid hormone cascade, such as deiodinase 2 and 3 (Dio2 and Dio3) are differentially regulated by the circadian clock and by changes of the ambient light. The expression level of Dio2 in adult rats (2-3 months of age) kept continuously in darkness is modulated by the circadian clock and is up-regulated by 2 fold at midday. When the diurnal ambient light was on, the expression level of Dio2 increased by 4-8 fold and a consequent increase of the related protein was detected around the nuclei of retinal photoreceptors and of neurons in inner and outer nuclear layers. The expression level of Dio3 had a different temporal pattern and was down-regulated by diurnal light. Our results suggest that DIO2 and DIO3 have a role not only in the developing retina but also in the adult retina and are powerfully regulated by light. As the thyroid hormone is a ligand inducible transcription factor controlling the expression of several target genes, the transcriptional activation of Dio2 could be a novel genomic component of light adaptation. PMID- 22039464 TI - A contributing role for anti-neuraminidase antibodies on immunity to pandemic H1N1 2009 influenza A virus. AB - BACKGROUND: Exposure to contemporary seasonal influenza A viruses affords partial immunity to pandemic H1N1 2009 influenza A virus (pH1N1) infection. The impact of antibodies to the neuraminidase (NA) of seasonal influenza A viruses to cross immunity against pH1N1 infection is unknown. METHODS AND RESULTS: Antibodies to the NA of different seasonal H1N1 influenza strains were tested for cross reactivity against A/California/04/09 (pH1N1). A panel of reverse genetic (rg) recombinant viruses was generated containing 7 genes of the H1N1 influenza strain A/Puerto Rico/08/34 (PR8) and the NA gene of either the pandemic H1N1 2009 strain (pH1N1) or one of the following contemporary seasonal H1N1 strains: A/Solomon/03/06 (rg Solomon) or A/Brisbane/59/07 (rg Brisbane). Convalescent sera collected from mice infected with recombinant viruses were measured for cross reactive antibodies to pH1N1 via Hemagglutinin Inhibition (HI) or Enzyme-Linked Immunosorbent Assay (ELISA). The ectodomain of a recombinant NA protein from the pH1N1 strain (pNA-ecto) was expressed, purified and used in ELISA to measure cross-reactive antibodies. Analysis of sera from elderly humans immunized with trivalent split-inactivated influenza (TIV) seasonal vaccines prior to 2009 revealed considerable cross-reactivity to pNA-ecto. High titers of cross-reactive antibodies were detected in mice inoculated with either rg Solomon or rg Brisbane. Convalescent sera from mice inoculated with recombinant viruses were used to immunize naive recipient Balb/c mice by passive transfer prior to challenge with pH1N1. Mice receiving rg California sera were better protected than animals receiving rg Solomon or rg Brisbane sera. CONCLUSIONS: The NA of contemporary seasonal H1N1 influenza strains induces a cross-reactive antibody response to pH1N1 that correlates with reduced lethality from pH1N1 challenge, albeit less efficiently than anti-pH1N1 NA antibodies. These findings demonstrate that seasonal NA antibodies contribute to but are not sufficient for cross reactive immunity to pH1N1. PMID- 22039465 TI - PI3K-dependent GSK3beta(Ser9)-phosphorylation is implicated in the intestinal epithelial cell wound-healing response. AB - INTRODUCTION: The ability of the intestinal epithelial barrier to respond to various injurious insults is an essential component of intestinal homeostasis. However, the molecular mechanisms responsible for wound-healing and repair in the intestine are poorly understood. The glycogen synthase kinase 3beta (GSK3beta) has been implicated in various biological processes such as cellular motility, cell spreading and recently inflammation. AIM: To investigate the role of GSK3beta in intestinal epithelial cell restitution. METHODS: Rat intestinal epithelial IEC18 cells were serum-starved for 16 to 24 h and wounded by multiple scraping. Akt(Ser473)-, GSK3beta(Ser9)- and RelA(Ser536)-phosphorylation were determined by Western blot using specific phospho-antibodies. The inhibitors AG1478 (1 uM) and Ly294002 (25 uM) were used to block EGF-R autophosphorylation and PI3K-activation, respectively. beta-Catenin/LEF/TCF dependent transcription was determined by reporter gene assay (TOP/FOP system). C-myc gene expression was evaluated by real-time RT-PCR. GSK3beta(-/-) mouse embryonic fibroblasts were used to characterize the role of GSK3beta in wounding-induced cell migration. RESULTS: Wounding induced GSK3beta(Ser9) phosphorylation in IEC-18 cells, which led to beta-catenin accumulation as well as nuclear translocation of beta catenin. beta-Catenin stabilization/nuclear translocation led to enhanced LEF-TCF transcriptional activity and subsequent c-myc mRNA accumulation in wounded cell monolayers. Blocking PI3K/Akt signaling with Ly294002 prevented wound-induced GSK3beta(Ser9) phosphorylation as well as beta-catenin nuclear translocation and significantly attenuated restitution. Additionally, wounding induced rapid NF kB(Ser536) phosphorylation, which was inhibited by AG1478, but not by Ly294002. GSK3beta(-/-) cells demonstrated significantly attenuated wound-induced restitution compared to wild-type cells. CONCLUSION: We conclude that PI3K mediated GSK3beta phosphorylation is involved in the intestinal epithelial wound healing response. Phosphorylation of GSK3beta may be important for intestinal restitution by promoting cell motility in response to wounding. PMID- 22039466 TI - A mechanism for synergy with combined mTOR and PI3 kinase inhibitors. AB - Dysregulation of the mammalian target of rapamycin (mTOR) signaling has been found in many human cancers, particularly those with loss of the tumor suppressor PTEN. However, mTORC1 inhibitors such as temsirolimus have only modest activity when used alone and may induce acquired resistance by activating upstream mTORC2 and Akt. Other tumors that do not depend upon PI3K/Akt/mTOR signaling for survival are primarily resistant. This study tested the hypothesis that the limited clinical efficacy of temsirolimus is due to a compensatory increase in survival signaling pathways downstream of Akt as well as an incomplete block of 4E-BP1-controlled proliferative processes downstream of mTOR. We explored the addition of a PI3K inhibitor to temsirolimus and identified the mechanism of combinatorial synergy. Proliferation assays revealed that BEZ235 (dual PI3K/mTOR inhibitor) or ZSTK474 (pan PI3K inhibitor) combined with temsirolimus synergistically inhibited cell growth compared to cells treated with any of the agents alone. Co-treatment resulted in G0/G1 cell cycle arrest and up-regulation of p27. Cell death occurred through massive autophagy and subsequent apoptosis. While molecular profiling revealed that, in most cases, sensitivity to temsirolimus alone was most marked in cells with high basal phospho-Akt resulting from PTEN inactivation, combining a PI3K inhibitor with temsirolimus prevented compensatory Akt phosphorylation and synergistically enhanced cell death regardless of PTEN status. Another molecular correlate of synergy was the finding that temsirolimus treatment alone blocks downstream S6 kinase signaling, but not 4E-BP1. Adding BEZ235 completely abrogated 4E-BP1 phosphorylation. We conclude that the addition of a PI3K inhibitor overcomes cellular resistance to mTORC1 inhibitors regardless of PTEN status, and thus substantially expands the molecular phenotype of tumors likely to respond. PMID- 22039467 TI - Inhibition of HERG potassium channels by celecoxib and its mechanism. AB - BACKGROUND: Celecoxib (Celebrex), a widely prescribed selective inhibitor of cyclooxygenase-2, can modulate ion channels independently of cyclooxygenase inhibition. Clinically relevant concentrations of celecoxib can affect ionic currents and alter functioning of neurons and myocytes. In particular, inhibition of Kv2.1 channels by celecoxib leads to arrhythmic beating of Drosophila heart and of rat heart cells in culture. However, the spectrum of ion channels involved in human cardiac excitability differs from that in animal models, including mammalian models, making it difficult to evaluate the relevance of these observations to humans. Our aim was to examine the effects of celecoxib on hERG and other human channels critically involved in regulating human cardiac rhythm, and to explore the mechanisms of any observed effect on the hERG channels. METHODS AND RESULTS: Celecoxib inhibited the hERG, SCN5A, KCNQ1 and KCNQ1/MinK channels expressed in HEK-293 cells with IC(50)s of 6.0 uM, 7.5 uM, 3.5 uM and 3.7 uM respectively, and the KCND3/KChiP2 channels expressed in CHO cells with an IC(50) of 10.6 uM. Analysis of celecoxib's effects on hERG channels suggested gating modification as the mechanism of drug action. CONCLUSIONS: The above channels play a significant role in drug-induced long QT syndrome (LQTS) and short QT syndrome (SQTS). Regulatory guidelines require that all new drugs under development be tested for effects on the hERG channel prior to first administration in humans. Our observations raise the question of celecoxib's potential to induce cardiac arrhythmias or other channel related adverse effects, and make a case for examining such possibilities. PMID- 22039468 TI - The minimal domain of adipose triglyceride lipase (ATGL) ranges until leucine 254 and can be activated and inhibited by CGI-58 and G0S2, respectively. AB - Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. ATGL specifically hydrolyzes triacylglycerols (TGs), thereby generating diacylglycerols and free fatty acids. ATGL's enzymatic activity is co-activated by the protein comparative gene identification-58 (CGI-58) and inhibited by the protein G0/G1 switch gene 2 (G0S2). The enzyme is predicted to act through a catalytic dyad (Ser47, Asp166) located within the conserved patatin domain (Ile10 Leu178). Yet, neither an experimentally determined 3D structure nor a model of ATGL is currently available, which would help to understand how CGI-58 and G0S2 modulate ATGL's activity. In this study we determined the minimal active domain of ATGL. This minimal fragment of ATGL could still be activated and inhibited by CGI-58 and G0S2, respectively. Furthermore, we show that this minimal domain is sufficient for protein-protein interaction of ATGL with its regulatory proteins. Based on these data, we generated a 3D homology model for the minimal domain. It strengthens our experimental finding that amino acids between Leu178 and Leu254 are essential for the formation of a stable protein domain related to the patatin fold. Our data provide insights into the structure-function relationship of ATGL and indicate higher structural similarities in the N-terminal halves of mammalian patatin-like phospholipase domain containing proteins, (PNPLA1, -2,- 3 and -5) than originally anticipated. PMID- 22039469 TI - Age shall not weary us: deleterious effects of self-regulation depletion are specific to younger adults. AB - Self-regulation depletion (SRD), or ego-depletion, refers to decrements in self regulation performance immediately following a different self-regulation demanding activity. There are now over a hundred studies reporting SRD across a broad range of tasks and conditions. However, most studies have used young student samples. Because prefrontal brain regions thought to subserve self regulation do not fully mature until 25 years of age, it is possible that SRD effects are confined to younger populations and are attenuated or disappear in older samples. We investigated this using the Stroop color task as an SRD induction and an autobiographical memory task as the outcome measure. We found that younger participants (<25 years) were susceptible to depletion effects, but found no support for such effects in an older group (40-65 years). This suggests that the widely-reported phenomenon of SRD has important developmental boundary conditions casting doubt on claims that it represents a general feature of human cognition. PMID- 22039470 TI - High levels of sediment contamination have little influence on estuarine beach fish communities. AB - While contaminants are predicted to have measurable impacts on fish assemblages, studies have rarely assessed this potential in the context of natural variability in physico-chemical conditions within and between estuaries. We investigated links between the distribution of sediment contamination (metals and PAHs), physico-chemical variables (pH, salinity, temperature, turbidity) and beach fish assemblages in estuarine environments. Fish communities were sampled using a beach seine within the inner and outer zones of six estuaries that were either heavily modified or relatively unmodified by urbanization and industrial activity. All sampling was replicated over two years with two periods sampled each year. Shannon diversity, biomass and abundance were all significantly higher in the inner zone of estuaries while fish were larger on average in the outer zone. Strong differences in community composition were also detected between the inner and outer zones. Few differences were detected between fish assemblages in heavily modified versus relatively unmodified estuaries despite high concentrations of sediment contaminants in the inner zones of modified estuaries that exceeded recognized sediment quality guidelines. Trends in species distributions, community composition, abundance, Shannon diversity, and average fish weight were strongly correlated to physico-chemical variables and showed a weaker relationship to sediment metal contamination. Sediment PAH concentrations were not significantly related to the fish assemblage. These findings suggest that variation in some physico-chemical factors (salinity, temperature, pH) or variables that co-vary with these factors (e.g., wave activity or grain size) have a much greater influence on this fish assemblage than anthropogenic stressors such as contamination. PMID- 22039471 TI - Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. AB - BACKGROUND: Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. Major CFS symptom relief during cancer chemotherapy in a patient with synchronous CFS and lymphoma spurred a pilot study of B-lymphocyte depletion using the anti CD20 antibody Rituximab, which demonstrated significant clinical response in three CFS patients. METHODS AND FINDINGS: In this double-blind, placebo controlled phase II study (NCT00848692), 30 CFS patients were randomised to either Rituximab 500 mg/m(2) or saline, given twice two weeks apart, with follow up for 12 months. Xenotropic murine leukemia virus-related virus (XMRV) was not detected in any of the patients. The responses generally affected all CFS symptoms. Major or moderate overall response, defined as lasting improvements in self-reported Fatigue score during follow-up, was seen in 10 out of 15 patients (67%) in the Rituximab group and in two out of 15 patients (13%) in the Placebo group (p = 0.003). Mean response duration within the follow-up period for the 10 responders to Rituximab was 25 weeks (range 8-44). Four Rituximab patients had clinical response durations past the study period. General linear models for repeated measures of Fatigue scores during follow-up showed a significant interaction between time and intervention group (p = 0.018 for self-reported, and p = 0.024 for physician-assessed), with differences between the Rituximab and Placebo groups between 6-10 months after intervention. The primary end-point, defined as effect on self-reported Fatigue score 3 months after intervention, was negative. There were no serious adverse events. Two patients in the Rituximab group with pre-existing psoriasis experienced moderate psoriasis worsening. CONCLUSION: The delayed responses starting from 2-7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact future research efforts in CFS. TRIAL REGISTRATION: ClinicalTrials.gov NCT00848692. PMID- 22039472 TI - Discrete redox signaling pathways regulate photosynthetic light-harvesting and chloroplast gene transcription. AB - In photosynthesis in chloroplasts, two related regulatory processes balance the actions of photosystems I and II. These processes are short-term, post translational redistribution of light-harvesting capacity, and long-term adjustment of photosystem stoichiometry initiated by control of chloroplast DNA transcription. Both responses are initiated by changes in the redox state of the electron carrier, plastoquinone, which connects the two photosystems. Chloroplast Sensor Kinase (CSK) is a regulator of transcription of chloroplast genes for reaction centres of the two photosystems, and a sensor of plastoquinone redox state. We asked whether CSK is also involved in regulation of absorbed light energy distribution by phosphorylation of light-harvesting complex II (LHC II). Chloroplast thylakoid membranes isolated from a CSK T-DNA insertion mutant and from wild-type Arabidopsis thaliana exhibit similar light- and redox-induced (32)P-labelling of LHC II and changes in 77 K chlorophyll fluorescence emission spectra, while room-temperature chlorophyll fluorescence emission transients from Arabidopsis leaves are perturbed by inactivation of CSK. The results indicate indirect, pleiotropic effects of reaction centre gene transcription on regulation of photosynthetic light-harvesting in vivo. A single, direct redox signal is transmitted separately to discrete transcriptional and post-translational branches of an integrated cytoplasmic regulatory system. PMID- 22039473 TI - Deactivation of the default mode network as a marker of impaired consciousness: an fMRI study. AB - Diagnosis of patients with a disorder of consciousness is very challenging. Previous studies investigating resting state networks demonstrate that 2 main features of the so-called default mode network (DMN), metabolism and functional connectivity, are impaired in patients with a disorder of consciousness. However, task-induced deactivation--a third main feature of the DMN--has not been explored in a group of patients. Deactivation of the DMN is supposed to reflect interruptions of introspective processes. Seventeen patients with unresponsive wakefulness syndrome (UWS, former vegetative state), 8 patients in minimally conscious state (MCS), and 25 healthy controls were investigated with functional magnetic resonance imaging during a passive sentence listening task. Results show that deactivation in medial regions is reduced in MCS and absent in UWS patients compared to healthy controls. Moreover, behavioral scores assessing the level of consciousness correlate with deactivation in patients. On single-subject level, all control subjects but only 2 patients in MCS and 6 with UWS exposed deactivation. Interestingly, all patients who deactivated during speech processing (except for one) showed activation in left frontal regions which are associated with conscious processing. Our results indicate that deactivation of the DMN can be associated with the level of consciousness by selecting those who are able to interrupt ongoing introspective processes. In consequence, deactivation of the DMN may function as a marker of consciousness. PMID- 22039474 TI - The existence of a hypnotic state revealed by eye movements. AB - Hypnosis has had a long and controversial history in psychology, psychiatry and neurology, but the basic nature of hypnotic phenomena still remains unclear. Different theoretical approaches disagree as to whether or not hypnosis may involve an altered mental state. So far, a hypnotic state has never been convincingly demonstrated, if the criteria for the state are that it involves some objectively measurable and replicable behavioural or physiological phenomena that cannot be faked or simulated by non-hypnotized control subjects. We present a detailed case study of a highly hypnotizable subject who reliably shows a range of changes in both automatic and volitional eye movements when given a hypnotic induction. These changes correspond well with the phenomenon referred to as the "trance stare" in the hypnosis literature. Our results show that this 'trance stare' is associated with large and objective changes in the optokinetic reflex, the pupillary reflex and programming a saccade to a single target. Control subjects could not imitate these changes voluntarily. For the majority of people, hypnotic induction brings about states resembling normal focused attention or mental imagery. Our data nevertheless highlight that in some cases hypnosis may involve a special state, which qualitatively differs from the normal state of consciousness. PMID- 22039475 TI - Simulation of near-infrared light absorption considering individual head and prefrontal cortex anatomy: implications for optical neuroimaging. AB - Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: 25.0+/-2.8 years), we characterized the individual distribution of tissue specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes (V(gray)) traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of (23.6+/-0.7) mm considering the deepest 5% of light. Of the detected photon packages scalp and bone absorbed (96.4+/-9.7)% and V(gray) absorbed (3.1+/-1.8)% of the energy. The mean V(gray) volume (1.1+/-0.4) cm3 was negatively correlated (r=-.76) with the SCD and frontal sinus volume (r=-.57) and was reduced by 41.5% in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD (r=.46) and the traversed frontal sinus volume (r=.43). Sulcal morphology had no significant impact on V(gray). Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance. PMID- 22039476 TI - Targeted cell fusion facilitates stable heterokaryon generation in vitro and in vivo. AB - Induced cell fusion has enabled several important discoveries, including the phenomenon of nuclear reprogramming and may yet be applied as a novel therapy for degenerative diseases. However, existing fusogens lack the efficiency required to enable investigation of the epigenetic modifications underlying nuclear reprogramming and the specificity required for clinical application. Here we present a chimeric measles hemagglutinin, Halpha7, which specifically and efficiently mediates the fusion of diverse cell types with skeletal muscle both in vitro and in vivo. When compared directly to polyethylene glycol, Halpha7 consistently generated a substantial increase in heterokaryon yield and exhibited insignificant levels of toxicity. Moreover, this increased fusion efficiency enabled detection of chromatin modifications associated with nuclear reprogramming following Halpha7-mediated fusion of human fibroblasts and mouse myotubes. Finally, Halpha7 was also capable of increasing the contribution of transplanted fibroblasts to skeletal muscle repair in vivo, suggesting that this strategy could be used for therapeutic gene delivery. PMID- 22039477 TI - Systematic analysis of gene expression differences between left and right atria in different mouse strains and in human atrial tissue. AB - BACKGROUND: Normal development of the atria requires left-right differentiation during embryonic development. Reduced expression of Pitx2c (paired-like homeodomain transcription factor 2, isoform c), a key regulator of left-right asymmetry, has recently been linked to atrial fibrillation. We therefore systematically studied the molecular composition of left and right atrial tissue in adult murine and human atria. METHODS: We compared left and right atrial gene expression in healthy, adult mice of different strains and ages by employing whole genome array analyses on freshly frozen atrial tissue. Selected genes with enriched expression in either atrium were validated by RT-qPCR and Western blot in further animals and in shock-frozen left and right atrial appendages of patients undergoing open heart surgery. RESULTS: We identified 77 genes with preferential expression in one atrium that were common in all strains and age groups analysed. Independent of strain and age, Pitx2c was the gene with the highest enrichment in left atrium, while Bmp10, a member of the TGFbeta family, showed highest enrichment in right atrium. These differences were validated by RT qPCR in murine and human tissue. Western blot showed a 2-fold left-right concentration gradient in PITX2 protein in adult human atria. Several of the genes and gene groups enriched in left atria have a known biological role for maintenance of healthy physiology, specifically the prevention of atrial pathologies involved in atrial fibrillation, including membrane electrophysiology, metabolic cellular function, and regulation of inflammatory processes. Comparison of the array datasets with published array analyses in heterozygous Pitx2c(+/-) atria suggested that approximately half of the genes with left-sided enrichment are regulated by Pitx2c. CONCLUSIONS: Our study reveals systematic differences between left and right atrial gene expression and supports the hypothesis that Pitx2c has a functional role in maintaining "leftness" in the atrium in adult murine and human hearts. PMID- 22039478 TI - Presence of cartilage stem/progenitor cells in adult mice auricular perichondrium. AB - BACKGROUND: Based on evidence from several other tissues, cartilage stem/progenitor cells in the auricular cartilage presumably contribute to tissue development or homeostasis of the auricle. However, no definitive studies have identified or characterized a stem/progenitor population in mice auricle. METHODOLOGY/PRINCIPAL FINDINGS: The 5-bromo-2'-deoxyuridine (BrdU) label retaining technique was used to label dividing cells in fetal mice. Observations one year following the labeling revealed that label-retaining cells (LRCs) were present specifically in auricular perichondrium at a rate of 0.08+/-0.06%, but LRCs were not present in chondrium. Furthermore, LRCs were successfully isolated and cultivated from auricular cartilage. Immunocytochemical analyses showed that LRCs express CD44 and integrin-alpha(5). These LRCs, putative stem/progenitor cells, possess clonogenicity and chondrogenic capability in vitro. CONCLUSIONS/SIGNIFICANCE: We have identified a population of putative cartilage stem/progenitor cells in the auricular perichondrium of mice. Further characterization and utilization of the cell population should improve our understanding of basic cartilage biology and lead to advances in cartilage tissue engineering and novel therapeutic strategies for patients with craniofacial defects, including long-term tissue restoration. PMID- 22039479 TI - Rapid maxillary anterior teeth retraction en masse by bone compression: a canine model. AB - OBJECTIVE: The present study sought to establish an animal model to study the feasibility and safety of rapid retraction of maxillary anterior teeth en masse aided by alveolar surgery in order to reduce orthodontic treatment time. METHOD: Extraction of the maxillary canine and alveolar surgery were performed on twelve adult beagle dogs. After that, the custom-made tooth-borne distraction devices were placed on beagles' teeth. Nine of the dogs were applied compression at 0.5 mm/d for 12 days continuously. The other three received no force as the control group. The animals were killed in 1, 14, and 28 days after the end of the application of compression. RESULTS: The tissue responses were assessed by craniometric measurement as well as histological examination. Gross alterations were evident in the experimental group, characterized by anterior teeth crossbite. The average total movements of incisors within 12 days were 4.63+/ 0.10 mm and the average anchorage losses were 1.25+/-0.12 mm. Considerable root resorption extending into the dentine could be observed 1 and 14 days after the compression. But after consolidation of 28 days, there were regenerated cementum on the dentine. There was no apparent change in the control group. No obvious tooth loosening, gingival necrosis, pulp degeneration, or other adverse complications appeared in any of the dogs. CONCLUSIONS: This is the first experimental study for testing the technique of rapid anterior teeth retraction en masse aided by modified alveolar surgery. Despite a preliminary animal model study, the current findings pave the way for the potential clinical application that can accelerate orthodontic tooth movement without many adverse complications. CLINICAL RELEVANCE: It may become a novel method to shorten the clinical orthodontic treatment time in the future. PMID- 22039480 TI - The Streptococcus sanguinis competence regulon is not required for infective endocarditis virulence in a rabbit model. AB - Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon in addition to DNA uptake, including virulence. We investigated this possibility in S. sanguinis. Strains deleted for the comCDE or comX master regulatory genes were created. Using a rabbit endocarditis model in conjunction with a variety of virulence assays, we determined that both mutants possessed infectivity equivalent to that of a virulent control strain, and that measures of disease were similar in rabbits infected with each strain. These results suggest that the com regulon is not required for S. sanguinis infective endocarditis virulence in this model. We propose that the different roles of the S. sanguinis, S. pneumoniae, and S. mutans com regulons in virulence can be understood in relation to the pathogenic mechanisms employed by each species. PMID- 22039481 TI - Imprinted genes that regulate early mammalian growth are coexpressed in somatic stem cells. AB - Lifelong, many somatic tissues are replenished by specialized adult stem cells. These stem cells are generally rare, infrequently dividing, occupy a unique niche, and can rapidly respond to injury to maintain a steady tissue size. Despite these commonalities, few shared regulatory mechanisms have been identified. Here, we scrutinized data comparing genes expressed in murine long term hematopoietic stem cells with their differentiated counterparts and observed that a disproportionate number were members of the developmentally-important, monoallelically expressed imprinted genes. Studying a subset, which are members of a purported imprinted gene network (IGN), we found their expression in HSCs rapidly altered upon hematopoietic perturbations. These imprinted genes were also predominantly expressed in stem/progenitor cells of the adult epidermis and skeletal muscle in mice, relative to their differentiated counterparts. The parallel down-regulation of these genes postnatally in response to proliferation and differentiation suggests that the IGN could play a mechanistic role in both cell growth and tissue homeostasis. PMID- 22039482 TI - Rac1-regulated endothelial radiation response stimulates extravasation and metastasis that can be blocked by HMG-CoA reductase inhibitors. AB - Radiotherapy (RT) plays a key role in cancer treatment. Although the benefit of ionizing radiation (IR) is well established, some findings raise the possibility that irradiation of the primary tumor not only triggers a killing response but also increases the metastatic potential of surviving tumor cells. Here we addressed the question of whether irradiation of normal cells outside of the primary tumor augments metastasis by stimulating the extravasation of circulating tumor cells. We show that IR exposure of human endothelial cells (EC), tumor cells (TC) or both increases TC-EC adhesion in vitro. IR-stimulated TC-EC adhesion was blocked by the HMG-CoA reductase inhibitor lovastatin. Glycyrrhizic acid from liquorice root, which acts as a Sialyl-Lewis X mimetic drug, and the Rac1 inhibitor NSC23766 also reduced TC-EC adhesion. To examine the in vivo relevance of these findings, tumorigenic cells were injected into the tail vein of immunodeficient mice followed by total body irradiation (TBI). The data obtained show that TBI dramatically enhances tumor cell extravasation and lung metastasis. This pro-metastatic radiation effect was blocked by pre-treating mice with lovastatin, glycyrrhizic acid or NSC23766. TBI of mice prior to tumor cell transplantation also stimulated metastasis, which was again blocked by lovastatin. The data point to a pro-metastatic trans-effect of RT, which likely rests on the endothelial radiation response promoting the extravasation of circulating tumor cells. Administration of the widely used lipid-lowering drug lovastatin prior to irradiation counteracts this process, likely by suppressing Rac1-regulated E-selectin expression following irradiation. The data support the concern that radiation exposure might increase the extravasation of circulating tumor cells and recommend co-administration of lipid-lowering drugs to avoid this adverse effect of ionizing radiation. PMID- 22039483 TI - Relative quantification of protein-protein interactions using a dual luciferase reporter pull-down assay system. AB - The identification and quantitative analysis of protein-protein interactions are essential to the functional characterization of proteins in the post-proteomics era. The methods currently available are generally time-consuming, technically complicated, insensitive and/or semi-quantitative. The lack of simple, sensitive approaches to precisely quantify protein-protein interactions still prevents our understanding of the functions of many proteins. Here, we develop a novel dual luciferase reporter pull-down assay by combining a biotinylated Firefly luciferase pull-down assay with a dual luciferase reporter assay. The biotinylated Firefly luciferase-tagged protein enables rapid and efficient isolation of a putative Renilla luciferase-tagged binding protein from a relatively small amount of sample. Both of these proteins can be quantitatively detected using the dual luciferase reporter assay system. Protein-protein interactions, including Fos-Jun located in the nucleus; MAVS-TRAF3 in cytoplasm; inducible IRF3 dimerization; viral protein-regulated interactions, such as MAVS MAVS and MAVS-TRAF3; IRF3 dimerization; and protein interaction domain mapping, are studied using this novel assay system. Herein, we demonstrate that this dual luciferase reporter pull-down assay enables the quantification of the relative amounts of interacting proteins that bind to streptavidin-coupled beads for protein purification. This study provides a simple, rapid, sensitive, and efficient approach to identify and quantify relative protein-protein interactions. Importantly, the dual luciferase reporter pull-down method will facilitate the functional determination of proteins. PMID- 22039484 TI - Quantifying and modeling birth order effects in autism. AB - Autism is a complex genetic disorder with multiple etiologies whose molecular genetic basis is not fully understood. Although a number of rare mutations and dosage abnormalities are specific to autism, these explain no more than 10% of all cases. The high heritability of autism and low recurrence risk suggests multifactorial inheritance from numerous loci but other factors also intervene to modulate risk. In this study, we examine the effect of birth rank on disease risk which is not expected for purely hereditary genetic models. We analyzed the data from three publicly available autism family collections in the USA for potential birth order effects and studied the statistical properties of three tests to show that adequate power to detect these effects exist. We detect statistically significant, yet varying, patterns of birth order effects across these collections. In multiplex families, we identify V-shaped effects where middle births are at high risk; in simplex families, we demonstrate linear effects where risk increases with each additional birth. Moreover, the birth order effect is gender-dependent in the simplex collection. It is currently unknown whether these patterns arise from ascertainment biases or biological factors. Nevertheless, further investigation of parental age-dependent risks yields patterns similar to those observed and could potentially explain part of the increased risk. A search for genes considering these patterns is likely to increase statistical power and uncover novel molecular etiologies. PMID- 22039485 TI - A low-cost library construction protocol and data analysis pipeline for Illumina based strand-specific multiplex RNA-seq. AB - The emergence of NextGen sequencing technology has generated much interest in the exploration of transcriptomes. Currently, Illumina Inc. (San Diego, CA) provides one of the most widely utilized sequencing platforms for gene expression analysis. While Illumina reagents and protocols perform adequately in RNA sequencing (RNA-seq), alternative reagents and protocols promise a higher throughput at a much lower cost. We have developed a low-cost and robust protocol to produce Illumina-compatible (GAIIx and HiSeq2000 platforms) RNA-seq libraries by combining several recent improvements. First, we designed balanced adapter sequences for multiplexing of samples; second, dUTP incorporation in 2(nd) strand synthesis was used to enforce strand-specificity; third, we simplified RNA purification, fragmentation and library size-selection steps thus drastically reducing the time and increasing throughput of library construction; fourth, we included an RNA spike-in control for validation and normalization purposes. To streamline informatics analysis for the community, we established a pipeline within the iPlant Collaborative. These scripts are easily customized to meet specific research needs and improve on existing informatics and statistical treatments of RNA-seq data. In particular, we apply significance tests for determining differential gene expression and intron retention events. To demonstrate the potential of both the library-construction protocol and data analysis pipeline, we characterized the transcriptome of the rice leaf. Our data supports novel gene models and can be used to improve current rice genome annotation. Additionally, using the rice transcriptome data, we compared different methods of calculating gene expression and discuss the advantages of a strand-specific approach to detect bona-fide anti-sense transcripts and to detect intron retention events. Our results demonstrate the potential of this low cost and robust method for RNA-seq library construction and data analysis. PMID- 22039486 TI - Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo. AB - Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 ul; 5*10(12) vg/ml) application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and CD31 immunoblotting. Real-time PCR quantified mRNA expression of pro- and anti-angiogenic genes. Corneal health in live animals was monitored with clinical, slit-lamp and optical coherence tomography biomicroscopic examinations. Selective decorin delivery into stroma showed significant 52% (p<0.05), 66% (p<0.001), and 63% (p<0.01) reduction at early (day 5), mid (day 10), and late (day 14) stages of CNV in decorin-delivered rabbit corneas compared to control (no decorin delivered) corneas in morphometric analysis. The H&E staining, lectin, collagen type IV, CD31 immunostaining (57-65, p<0.5), and CD31 immunoblotting (62-67%, p<0.05) supported morphometric findings. Quantitative PCR studies demonstrated decorin gene therapy down-regulated expression of VEGF, MCP1 and angiopoietin (pro-angiogenic) and up-regulated PEDF (anti-angiogenic) genes. The clinical, biomicroscopy and transmission electron microscopy studies revealed that AAV5-mediated decorin gene therapy is safe for the cornea. Tissue-targeted AAV5-mediated decorin gene therapy decreases CNV with no major side effects, and could potentially be used for treating patients. PMID- 22039487 TI - Deterioration of the Galphao vomeronasal pathway in sexually dimorphic mammals. AB - In mammals, social and sexual behaviours are largely mediated by the vomeronasal system (VNS). The accessory olfactory bulb (AOB) is the first synaptic locus of the VNS and ranges from very large in Caviomorph rodents, small in carnivores and ungulates, to its complete absence in apes, elephants, most bats and aquatic species. Two pathways have been described in the VNS of mammals. In mice, vomeronasal neurons expressing Galphai2 protein project to the rostral portion of the AOB and respond mostly to small volatile molecules, whereas neurons expressing Galphao project to the caudal AOB and respond mostly to large non volatile molecules. However, the Galphao-expressing pathway is absent in several species (horses, dogs, musk shrews, goats and marmosets) but no hypotheses have been proposed to date to explain the loss of that pathway. We noted that the species that lost the Galphao pathway belong to Laurasiatheria and Primates lineages, both clades with ubiquitous sexual dimorphisms across species. To assess whether similar events of Galphao pathway loss could have occurred convergently in dimorphic species we studied G-protein expression in the AOB of two species that independently evolved sexually dimorphic traits: the California ground squirrel Spermophilus beecheyi (Rodentia; Sciurognathi) and the cape hyrax Procavia capensis (Afrotheria; Hyracoidea). We found that both species show uniform expression of Galphai2-protein throughout AOB glomeruli, while Galphao expression is restricted to main olfactory glomeruli only. Our results suggest that the degeneration of the Galphao-expressing vomeronasal pathway has occurred independently at least four times in Eutheria, possibly related to the emergence of sexual dimorphisms and the ability of detecting the gender of conspecifics at distance. PMID- 22039488 TI - Genetic association of multiple sclerosis with the marker rs391745 near the endogenous retroviral locus HERV-Fc1: analysis of disease subtypes. AB - We have previously described the occurrence of multiple sclerosis (MS) to be associated with human endogenous retroviruses, specifically the X-linked viral locus HERV-Fc1. The aim of this study was to investigate a possible association of the HERV-Fc1 locus with subtypes of MS. MS patients are generally subdivided into three categories: Remitting/Relapsing and Secondary Progressive, which together constitute Bout Onset MS, and Primary Progressive. In this study of 1181 MS patients and 1886 controls we found that Bout Onset MS was associated with the C-allele of the marker rs391745 near the HERV-Fc1 locus (p = 0.003), while primary progressive disease was not. The ability to see genetic differences between subtypes of MS near this gene speaks for the involvement of the virus HERV-Fc1 locus in modifying the disease course of MS. PMID- 22039489 TI - S-diclofenac protects against doxorubicin-induced cardiomyopathy in mice via ameliorating cardiac gap junction remodeling. AB - Hydrogen sulfide (H(2)S), as a novel gaseous mediator, plays important roles in mammalian cardiovascular tissues. In the present study, we investigated the cardioprotective effect of S-diclofenac (2-[(2,6-dichlorophenyl)amino] benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester), a novel H(2)S releasing derivative of diclofenac, in a murine model of doxorubicin-induced cardiomyopathy. After a single dose injection of doxorubicin (15 mg/kg, i.p.), male C57BL/6J mice were given daily treatment of S-diclofenac (25 and 50 umol/kg, i.p.), diclofenac (25 and 50 umol/kg, i.p.), NaHS (50 umol/kg, i.p.), or same volume of vehicle. The cardioprotective effect of S-diclofenac was observed after 14 days. It showed that S-diclofenac, but not diclofenac, dose-dependently inhibited the doxorubicin-induced downregulation of cardiac gap junction proteins (connexin 43 and connexin 45) and thus reversed the remodeling of gap junctions in hearts. It also dose-dependently suppressed doxorubicin-induced activation of JNK in hearts. Furthermore, S-diclofenac produced a dose-dependent anti inflammatory and anti-oxidative effect in this model. As a result, S-diclofenac significantly attenuated doxorubicin-related cardiac injury and cardiac dysfunction, and improved the survival rate of mice with doxorubicin-induced cardiomyopathy. These effects of S-diclofenac were mimicked in large part by NaHS. Therefore, we propose that H(2)S released from S-diclofenac in vivo contributes to the protective effect in doxorubicin-induced cardiomyopathy. These data also provide evidence for a critical role of H(2)S in the pathogenesis of doxorubicin-induced cardiomyopathy. PMID- 22039490 TI - Quantitative proteomics of Spodoptera frugiperda cells during growth and baculovirus infection. AB - Baculovirus infection of Spodoptera frugiperda cells is a system of choice to produce a range of recombinant proteins, vaccines and, potentially, gene therapy vectors. While baculovirus genomes are well characterized, the genome of S. frugiperda is not sequenced and the virus-host molecular interplay is sparsely known. Herein, we describe the application of stable isotope labeling by amino acids in cell culture (SILAC) to obtain the first comparative proteome quantitation of S. frugiperda cells during growth and early baculovirus infection. The proteome coverage was maximized by compiling a search database with protein annotations from insect species. Of interest were differentially proteins related to energy metabolism, endoplasmic reticulum and oxidative stress, yet not investigated in the scope of baculovirus infection. Further, the reduced expression of key viral-encoded proteins early in the infection cycle is suggested to be related with decreased viral replication at high cell density culture. These findings have implications for virological research and improvement of baculovirus-based bioprocesses. PMID- 22039491 TI - The group-level consequences of sexual conflict in multigroup populations. AB - In typical sexual conflict scenarios, males best equipped to exploit females are favored locally over more prudent males, despite reducing female fitness. However, local advantage is not the only relevant form of selection. In multigroup populations, groups with less sexual conflict will contribute more offspring to the next generation than higher conflict groups, countering the local advantage of harmful males. Here, we varied male aggression within- and between-groups in a laboratory population of water striders and measured resulting differences in local population growth over a period of three weeks. The overall pool fitness (i.e., adults produced) of less aggressive pools exceeded that of high aggression pools by a factor of three, with the high aggression pools essentially experiencing no population growth over the course of the study. When comparing the fitness of individuals across groups, aggression appeared to be under stabilizing selection in the multigroup population. The use of contextual analysis revealed that overall stabilizing selection was a product of selection favoring aggression within groups, but selected against it at the group-level. Therefore, this report provides further evidence to show that what evolves in the total population is not merely an extension of within-group dynamics. PMID- 22039492 TI - Identification of direct target engagement biomarkers for kinase-targeted therapeutics. AB - Pharmacodynamic (PD) biomarkers are an increasingly valuable tool for decision making and prioritization of lead compounds during preclinical and clinical studies as they link drug-target inhibition in cells with biological activity. They are of particular importance for novel, first-in-class mechanisms, where the ability of a targeted therapeutic to impact disease outcome is often unknown. By definition, proximal PD biomarkers aim to measure the interaction of a drug with its biological target. For kinase drug discovery, protein substrate phosphorylation sites represent candidate PD biomarkers. However, substrate phosphorylation is often controlled by input from multiple converging pathways complicating assessment of how potently a small molecule drug hits its target based on substrate phoshorylation measurements alone. Here, we report the use of quantitative, differential mass-spectrometry to identify and monitor novel drug regulated phosphorylation sites on target kinases. Autophosphorylation sites constitute clinically validated biomarkers for select protein tyrosine kinase inhibitors. The present study extends this principle to phosphorylation sites in serine/threonine kinases looking beyond the T-loop autophosphorylation site. Specifically, for the 3'-phosphoinositide-dependent protein kinase 1 (PDK1), two phospho-residues p-PDK1(Ser410) and p-PDK1(Thr513) are modulated by small molecule PDK1 inhibitors, and their degree of dephosphorylation correlates with inhibitor potency. We note that classical, ATP-competitive PDK1 inhibitors do not modulate PDK1 T-loop phosphorylation (p-PDK1(Ser241)), highlighting the value of an unbiased approach to identify drug target-regulated phosphorylation sites as these are complementary to pathway PD biomarkers. Finally, we extend our analysis to another protein Ser/Thr kinase, highlighting a broader utility of our approach for identification of kinase drug-target engagement biomarkers. PMID- 22039493 TI - Defining obesity cut-off points for migrant South Asians. AB - BACKGROUND: Body mass index (BMI) and waist circumference (WC) are used to define cardiovascular and type 2 diabetes risk. We aimed to derive appropriate BMI and WC obesity cut-off points in a migrant South Asian population. METHODS: 4688 White Europeans and 1333 South Asians resident in the UK aged 40-75 years inclusive were screened for type 2 diabetes. Principal components analysis was used to derive a glycaemia, lipid, and a blood pressure factor. Regression models for each factor, adjusted for age and stratified by sex, were used to identify BMI and WC cut-off points in South Asians that correspond to those defined for White Europeans. FINDINGS: For South Asian males, derived BMI obesity cut-off points equivalent to 30.0 kg/m(2) in White Europeans were 22.6 kg/m(2) (95% Confidence Interval (95% CI) 20.7 kg/m(2) to 24.5 kg/m(2)) for the glycaemia factor, 26.0 kg/m(2) (95% CI 24.7 kg/m(2) to 27.3 kg/m(2)) for the lipid factor, and 28.4 kg/m(2) (95% CI 26.5 kg/m(2) to 30.4 kg/m(2)) for the blood pressure factor. For WC, derived cut-off points for South Asian males equivalent to 102 cm in White Europeans were 83.8 cm (95% CI 79.3 cm to 88.2 cm) for the glycaemia factor, 91.4 cm (95% CI 86.9 cm to 95.8 cm) for the lipid factor, and 99.3 cm (95% CI 93.3 cm to 105.2 cm) for the blood pressure factor. Lower ethnicity cut off points were seen for females for both BMI and WC. CONCLUSIONS: Substantially lower obesity cut-off points are needed in South Asians to detect an equivalent level of dysglycemia and dyslipidemia as observed in White Europeans. South Asian ethnicity could be considered as a similar level of risk as obesity (in White Europeans) for the development of type 2 diabetes. PMID- 22039494 TI - Identification of hypoxia-induced genes in human SGBS adipocytes by microarray analysis. AB - Hypoxia in adipose tissue is suggested to be involved in the development of a chronic mild inflammation, which in obesity can further lead to insulin resistance. The effect of hypoxia on gene expression in adipocytes appears to play a central role in this inflammatory response observed in obesity. However, the global impact of hypoxia on transcriptional changes in human adipocytes is unclear. Therefore, we compared gene expression profiles of human Simpson-Golabi Behmel syndrome (SGBS) adipocytes under normoxic or hypoxic conditions to detect hypoxia-responsive genes in adipocytes by using whole human genome microarrays. Microarray analysis showed more than 500 significantly differentially regulated mRNAs after incubation of the cells under low oxygen levels. To gain further insight into the biological processes, hypoxia-regulated genes after 16 hours of hypoxia were classified according to their function. We identified an enrichment of genes involved in important biological processes such as glycolysis, response to hypoxia, regulation of cellular component movement, response to nutrient levels, regulation of cell migration, and transcription regulator activity. Real time PCR confirmed eight genes to be consistently upregulated in response to 3, 6 and 16 hours of hypoxia. For adipocytes the hypoxia-induced regulation of these genes is shown here for the first time. Moreover in six of these eight genes we identified HIF response elements in the proximal promoters, specific for the HIF transcription factor family members HIF1A and HIF2A. In the present study, we demonstrated that hypoxia has an extensive effect on gene expression of SGBS adipocytes. In addition, the identified hypoxia-regulated genes are likely involved in the regulation of obesity, the incidence of type 2 diabetes, and the metabolic syndrome. PMID- 22039495 TI - High-dose siRNAs upregulate mouse Eri-1 at both transcription and posttranscription levels. AB - The eri-1 gene encodes a 3' exonuclease that can negatively regulate RNA interference via siRNase activity. High-dose siRNAs (hd-siRNAs) can enhance Eri-1 expression, which in return degrade siRNAs and greatly reduces RNAi efficiency. Here we report that hd-siRNAs induce mouse Eri-1 (meri-1) expression through the recruitment of Sp1, Ets-1, and STAT3 to the meri-1 promoter and the formation of an Sp1-Ets-1-STAT3 complex. In addition, hd-siRNAs also abolish the 3' untranslated region (UTR) mediated posttranscriptional repression of meri-1. Our findings demonstrate the molecular mechanism underlying the upregulation of meri 1 by hd-siRNA. PMID- 22039496 TI - Cues paired with either rapid or slower self-administered cocaine injections acquire similar conditioned rewarding properties. AB - The faster drugs of abuse reach the brain, the more addictive they can be. It is not known why this is. Environmental stimuli associated with drugs can promote the development and persistence of addiction by invigorating and precipitating drug-seeking behaviour. We determined, therefore, whether cues associated with the self-administration of rapidly delivered cocaine (injected intravenously over 5 versus 90 seconds) would acquire greater conditioned rewarding properties, as assessed by the performance of an operant response reinforced solely by the cues. Rats nose-poked for intravenous cocaine infusions delivered either over 5 or 90 seconds. Discrete visual cues accompanied each infusion. The rats could then press a lever to obtain the cues--now a conditioned reward--or an inactive lever. Rats in both the 5- and 90-second groups pressed more on the active versus inactive lever following extensive (24 sessions) but not following limited (3 sessions) self-administration training. There were no group differences in this behaviour. Following withdrawal from cocaine self-administration, lever discrimination progressively abated in both groups and was lost by withdrawal day 30. However, the rewarding properties of the cues were not "forgotten" because on withdrawal days 32-33, amphetamine selectively enhanced active-lever pressing, and did so to a similar extent in both groups. Thus, cues paired with rapid or slower cocaine delivery acquire similar conditioned rewarding properties. We conclude, therefore, that the rapid delivery of cocaine to the brain promotes addiction by mechanisms that might not involve a greater ability of drug cues to control behaviour. PMID- 22039497 TI - Habitat correlates of the red panda in the temperate forests of Bhutan. AB - Anthropogenic activities and associated global climate change are threatening the biodiversity in the Himalayas against a backdrop of poor knowledge of the region's threatened species. The red panda (Ailurus fulgens) is a threatened mammal confined to the eastern Himalayas, and because of Bhutan's central location in the distributional range of red pandas, its forests are integral to the long-term viability of wild populations. Detailed habitat requirements of the red panda are largely speculative, and there is virtually no ecological information available on this species in Bhutan. Between 2007 and 2009, we established 615 presence/absence plots in a systematic sampling of resident habitat types within Jigme Dorji and Thrumshingla National Parks, Bhutan, to investigate broad and fine-scale red panda habitat associations. Additional locality records of red pandas were obtained from interviewing 664 park residents. Red pandas were generally confined to cool broadleaf and conifer forests from 2,110-4,389 m above sea level (asl), with the majority of records between 2,400-3,700 m asl on south and east-facing slopes. At a finer scale, multivariate analysis revealed that red pandas were strongly associated with old growth Bhutan Fir (Abies densa) forest dominated by a dense cover of Yushania and Arundanaria bamboo with a high density of fallen logs and tree stumps at ground level; a high density of trees, dead snags, and rhododendron shrubs in the mid storey; and locations that were close to water. Because Bhutan's temperate forests that encompass prime red panda habitat are also integral to human subsistence and socio-economic development, there exists an inadvertent conflict between the needs of people and red pandas. As such, careful sustainable management of Bhutan's temperate forests is necessary if a balance is to be met between the socioeconomic needs of people and the conservation goals for red pandas. PMID- 22039498 TI - Undirected (solitary) birdsong in female and male blue-capped cordon-bleus (Uraeginthus cyanocephalus) and its endocrine correlates. AB - BACKGROUND: Birdsong is a popular model system in research areas such as vocal communication, neuroethology or neuroendocrinology of behaviour. As most research has been conducted on species with male-only song production, the hormone dependency of male song is well established. However, female singing and its mechanisms are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: We characterised the song and its endocrine correlates of blue-capped cordon-bleus (Uraeginthus cyanocephalus), a species in which both sexes sing. Like other estrildids, they produce directed song during courtship and undirected (or solitary) song in isolation, i.e. when the mate is not visible or absent. We compare solitary song of blue-capped cordon-bleus to published descriptions of the song of its relative, the zebra finch (Taeniopygia guttata). Solitary song of cordon-bleus shared some overall song features with that of zebra finches but differed in spectro-temporal song features, sequential stereotypy and sequential organisation. The song of cordon-bleus was dimorphic with respect to the larger size of syllable repertoires, the higher song duration and the lower variability of pitch goodness (measuring the pureness of harmonic sounds) in males. However, in both sexes the overall plasma testosterone concentrations were low (ca. 300 pg/ml) and did not correlate with the sexually dimorphic song motor pattern. Despite such low concentrations, the increase in the rate of solitary song coincided with an increase in the level of testosterone. Furthermore, the latency to start singing after the separation from the mate was related to hormone levels. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the occurrence of solitary song but not its motor pattern might be under the control of testosterone in female and male cordon-bleus. PMID- 22039499 TI - Teleological reasoning in 4-month-old infants: pupil dilations and contextual constraints. AB - Four-month-old infants were presented with feeding actions performed in a rational or irrational manner. Infants reacted to the irrational feeding actions by dilating their pupils, but only in the presence of rich contextual constraints. The study demonstrates that teleological processes are online at 4 months of age and illustrates the usefulness of pupil dilations as a measure of social cognitive processes early in infancy. PMID- 22039500 TI - Human leukocyte antigen (HLA) class I restricted epitope discovery in yellow fewer and dengue viruses: importance of HLA binding strength. AB - Epitopes from all available full-length sequences of yellow fever virus (YFV) and dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV epitopes were selected using the EpiSelect algorithm to allow for optimal coverage of viral strains. The selected predicted epitopes were synthesized and approximately 75% were found to bind the predicted restricting HLA molecule with an affinity, K(D), stronger than 500 nM. The immunogenicity of 25 HLA-A*02:01, 28 HLA-A*24:02 and 28 HLA-B*07:02 binding peptides was tested in three HLA-transgenic mice models and led to the identification of 17 HLA-A*02:01, 4 HLA-A*2402 and 4 HLA-B*07:02 immunogenic peptides. The immunogenic peptides bound HLA significantly stronger than the non immunogenic peptides. All except one of the immunogenic peptides had K(D) below 100 nM and the peptides with K(D) below 5 nM were more likely to be immunogenic. In addition, all the immunogenic peptides that were identified as having a high functional avidity had K(D) below 20 nM. A*02:01 transgenic mice were also inoculated twice with the 17DD YFV vaccine strain. Three of the YFV A*02:01 restricted peptides activated T-cells from the infected mice in vitro. All three peptides that elicited responses had an HLA binding affinity of 2 nM or less. The results indicate the importance of the strength of HLA binding in shaping the immune response. PMID- 22039501 TI - Identification and characterisation of an iron-responsive candidate probiotic. AB - BACKGROUND: Iron is an essential cofactor in almost all biological systems. The lactic acid bacteria (LAB), frequently employed as probiotics, are unusual in having little or no requirement for iron. Iron in the human body is sequestered by transferrins and lactoferrin, limiting bacterial growth. An increase in the availability of iron in the intestine by bleeding, surgery, or under stress leads to an increase in the growth and virulence of many pathogens. Under these high iron conditions, LAB are rapidly out-competed; for the levels of probiotic bacteria to be maintained under high iron conditions they must be able to respond by increasing growth rate to compete with the normal flora. Despite this, iron responsive genera are poorly characterised as probiotics. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that a panel of probiotics are not able to respond to increased iron availability, and identify an isolate of Streptococcus thermophilus that can increase growth rate in response to increased iron availability. The isolate of S. thermophilus selected was able to reduce epithelial cell death as well as NF-kappaB signalling and IL-8 production triggered by pathogens. It was capable of crossing an epithelial cell barrier in conjunction with E. coli and downregulating Th1 and Th17 responses in primary human intestinal leukocytes. CONCLUSIONS/SIGNIFICANCE: We propose that an inability to compete with potential pathogens under conditions of high iron availability such as stress and trauma may contribute to the lack of efficacy of many LAB-based probiotics in treating disease. Therefore, we offer an alternative paradigm which considers that probiotics should be able to be competitive during periods of intestinal bleeding, trauma or stress. PMID- 22039502 TI - Molecular-genetic mapping of zebrafish mutants with variable phenotypic penetrance. AB - Forward genetic screens in vertebrates are powerful tools to generate models relevant to human diseases, including neuropsychiatric disorders. Variability in phenotypic penetrance and expressivity is common in these disorders and behavioral mutant models, making their molecular-genetic mapping a formidable task. Using a 'phenotyping by segregation' strategy, we molecularly map the hypersensitive zebrafish houdini mutant despite its variable phenotypic penetrance, providing a generally applicable strategy to map zebrafish mutants with subtle phenotypes. PMID- 22039503 TI - Is mitochondrial tRNA(phe) variant m.593T>C a synergistically pathogenic mutation in Chinese LHON families with m.11778G>A? AB - Mitochondrial transfer RNA (mt-tRNA) mutations have been reported to be associated with a variety of diseases. In a previous paper that studied the mtDNA background effect on clinical expression of Leber's hereditary optic neuropathy (LHON) in 182 Chinese families with m.11778G>A, we found a strikingly high frequency (7/182) of m.593T>C in the mitochondrially encoded tRNA phenylalanine (MT-TF) gene in unrelated LHON patients. To determine the potential role of m.593T>C in LHON, we compared the frequency of this variant in 479 LHON patients with m.11778G>A, 843 patients with clinical features of LHON but without the three known primary mutations, and 2374 Han Chinese from the general populations. The frequency of m.593T>C was higher in LHON patients (14/479) than in suspected LHON subjects (12/843) or in general controls (49/2374), but the difference was not statistically significant. The overall penetrance of LHON in families with both m.11778G>A and m.593T>C (44.6%) was also substantially higher than that of families with only m.11778G>A (32.9%) (P = 0.083). Secondary structure prediction of the MT-TF gene with the wild type or m.593T>C showed that this nucleotide change decreases the free energy. Electrophoretic mobility of the MT-TF genes with the wild type or m.593T>C transcribed in vitro further confirmed the change of secondary structure in the presence of this variant. Although our results could suggest a modest synergistic effect of variant m.593T>C on the LHON causing mutation m.11778G>A, the lack of statistical significance probably due to the relatively small sample size analyzed, makes necessary more studies to confirm this effect. PMID- 22039504 TI - Evidence of MexT-independent overexpression of MexEF-OprN multidrug efflux pump of Pseudomonas aeruginosa in presence of metabolic stress. AB - BACKGROUND: The Pseudomonas aeruginosa MexEF-OprN efflux pump confers resistance to clinically significant antibiotics. Regulation of mexEF-oprN operon expression is multifaceted with the MexT activator being one of the most prominent regulatory proteins. METHODOLOGY: We have exploited the impaired metabolic fitness of a P. aeruginosa mutant strain lacking several efflux pump of the resistance nodulation cell division superfamily and the TolC homolog OpmH, and isolated derivatives (large colony variants) that regained fitness by incubation on nutrient-rich medium in the absence of antibiotics. Although the mexEF-oprN operon is uninducible in this mutant due to a 8-bp mexT insertion present in some P. aeruginosa PAO1 strains, the large colony variants expressed high levels of MexEF-OprN. Unlike large colony variants obtained after plating on antibiotic containing medium which expressed mexEF-oprN in a MexT-dependent fashion as evidenced by clean excision of the 8-bp insertion from mexT, mexEF-oprN expression was MexT-independent in the large colony variants obtained by plating on LB alone since the mexT gene remained inactivated. A search for possible regulators of mexEF-oprN expression using transposon mutagenesis and genomic library expression approaches yielded several candidates but proved inconclusive. SIGNIFICANCE: Our results show that antibiotic and metabolic stress lead to up regulation of MexEF-OprN expression via different mechanisms and that MexEF-OprN does not only extrude antimicrobials but rather serves other important metabolic functions. PMID- 22039505 TI - Increased number of Tc17 and correlation with Th17 cells in patients with immune thrombocytopenia. AB - BACKGROUND: IL-17-secreting CD8+ T cells (Tc17 subset) have recently been defined as a subpopulation of effector T cells implicated in the pathogenesis of autoimmune diseases. The role of Tc17 and correlation with Th17 cells in the pathophysiology of immune thrombocytopenia (ITP) remain unsettled. DESIGN AND METHODS: We studied 47 ITP patients (20 newly-diagnosed and 27 with complete response) and 34 healthy controls. IL-17-producing CD3+CD8+ cells (Tc17) and IL 17-producing CD3+CD8- cells (Th17) were evaluated by flow cytometry and expressed as a percentage of the total number of CD3+ cells. Specific anti-platelet glycoprotein (GP) GPIIb/IIIa and/or GPIb/IX autoantibodies were measured by modified monoclonal antibody specific immobilization of platelet antigens. Peripheral blood mononuclear cells of ITP patients were isolated, incubated in the presence of 0, 0.25, 0.5, or 1 umol/L of dexamethasone for 72 h, and collected to detect Tc17 and Th17 cells by flow cytometric analysis. RESULTS: IL 17 was expressed on CD3+CD8- and CD3+CD8+ T cells. The percentages of Tc17 and Th17 cells in newly-diagnosed patients were significantly elevated compared to controls, and Tc17 was decreased after clinical treatment. The Th17?Tc17 ratio was significantly lower in newly-diagnosed patients compared with controls, and was increased in patients who had complete response. There was a significantly positive correlation between Tc17 and Th17 cells in the control group, but not in the ITP patients. A positive correlation existed between Tc17 and the CD8?CD4 ratio, as well as CD8+ cells in patients with ITP. The frequencies of Tc17 were marginally higher in autoantibody-negative patients than autoantibody-positive patients. Moreover, both Tc17 and Th17 cell percentages decreased as the concentration of dexamethasone in the culture media increased in ITP patients. CONCLUSIONS: Tc17 and the Th17 subset are involved in the immunopathology of ITP. Blocking the abnormally increased number of Tc17 may be a reasonable therapeutic strategy for ITP. PMID- 22039506 TI - Elevated level of Wnt5a protein in localized prostate cancer tissue is associated with better outcome. AB - BACKGROUND: Wnt5a is a non-canonical secreted glycoprotein of the Wnt family that plays an important role in cancer development and progression. Previous studies report that Wnt5a is upregulated in prostate cancer and suggested that Wnt5a affects migration and invasion of prostate tumor cell. This study aimed to evaluate the prognostic value of Wnt5a protein expression in prostate cancer tissue and its potential to predict outcome after radical prostatectomy in patients with localized prostate cancer. METHODOLOGY AND RESULTS: Immunohistochemical analysis of a tissue microarray containing prostate specimens of 503 patients with localized prostate cancer showed significantly higher Wnt5a protein expression in cancer compared to benign cores from the same patients (p<0.0001). Patients with high expression of Wnt5a protein had significantly better outcome in terms of time to biochemical recurrence compared to patients with low expression levels (p = 0.001, 95%CI 1.361-3.570, Hazard's ratio 2.204). A combination of high Wnt5a expression with low levels of Ki-67 or androgen receptor expression had even better outcome compared to all other groups. Furthermore, we found that Wnt5a expression significantly correlated with VEGF and with Ki-67 and androgen receptor expression, although not highly significant. In vitro, we demonstrated that recombinant Wnt5a decreased invasion of 22Rv1 and DU145 cells and that siRNA knockdown of endogenous Wnt5a protein led to increased invasion of 22Rv1 and LNCaP cells. CONCLUSION: We demonstrate that preserved overexpression of Wnt5a protein in patients with localized prostate cancer predicts a favorable outcome after surgery. This finding together with our in vitro data demonstrating the ability of Wnt5a to impair the invasive properties of prostate cancer cells, suggests a tumor suppressing effect of Wnt5a in localized prostate cancer. These results indicate that Wnt5a can be used as a predictive marker and that it also is a plausible therapeutic target for treatment of localized prostate cancer. PMID- 22039507 TI - Def6 is required for convergent extension movements during zebrafish gastrulation downstream of Wnt5b signaling. AB - During gastrulation, convergent extension (CE) cell movements are regulated through the non-canonical Wnt signaling pathway. Wnt signaling results in downstream activation of Rho GTPases that in turn regulate actin cytoskeleton rearrangements essential for co-ordinated CE cell movement. Rho GTPases are bi molecular switches that are inactive in their GDP-bound stage but can be activated to bind GTP through guanine nucleotide exchange factors (GEFs). Here we show that def6, a novel GEF, regulates CE cell movement during zebrafish gastrulation. Def6 morphants exhibit broadened and shortened body axis with normal cell fate specification, reminiscent of the zebrafish mutants silberblick and pipetail that lack Wnt11 or Wnt5b, respectively. Indeed, def6 morphants phenocopy Wnt5b mutants and ectopic overexpression of def6 essentially rescues Wnt5b morphants, indicating a novel role for def6 as a central GEF downstream of Wnt5b signaling. In addition, by knocking down both def6 and Wnt11, we show that def6 synergises with the Wnt11 signaling pathway. PMID- 22039508 TI - Homologous expression of a subcomplex of Pyrococcus furiosus hydrogenase that interacts with pyruvate ferredoxin oxidoreductase. AB - Hydrogen gas is an attractive alternative fuel as it is carbon neutral and has higher energy content per unit mass than fossil fuels. The biological enzyme responsible for utilizing molecular hydrogen is hydrogenase, a heteromeric metalloenzyme requiring a complex maturation process to assemble its O(2) sensitive dinuclear-catalytic site containing nickel and iron atoms. To facilitate their utility in applied processes, it is essential that tools are available to engineer hydrogenases to tailor catalytic activity and electron carrier specificity, and decrease oxygen sensitivity using standard molecular biology techniques. As a model system we are using hydrogen-producing Pyrococcus furiosus, which grows optimally at 100 degrees C. We have taken advantage of a recently developed genetic system that allows markerless chromosomal integrations via homologous recombination. We have combined a new gene marker system with a highly-expressed constitutive promoter to enable high-level homologous expression of an engineered form of the cytoplasmic NADP-dependent hydrogenase (SHI) of P. furiosus. In a step towards obtaining 'minimal' hydrogenases, we have successfully produced the heterodimeric form of SHI that contains only two of the four subunits found in the native heterotetrameric enzyme. The heterodimeric form is highly active (150 units mg(-1) in H(2) production using the artificial electron donor methyl viologen) and thermostable (t(1/2) ~0.5 hour at 90 degrees C). Moreover, the heterodimer does not use NADPH and instead can directly utilize reductant supplied by pyruvate ferredoxin oxidoreductase from P. furiosus. The SHI heterodimer and POR therefore represent a two-enzyme system that oxidizes pyruvate and produces H(2) in vitro without the need for an intermediate electron carrier. PMID- 22039509 TI - Human embryonic stem cells derived from embryos at different stages of development share similar transcription profiles. AB - We have derived hESC from biopsied blastomeres of cleavage stage embryos under virtually the same conditions we used for the derivation of hESC lines from inner cell mass of blastocyst stage embryos. Blastomere-derived hESC lines exhibited all the standard characteristics of hESC including undifferentiated proliferation, genomic stability, expression of pluripotency markers and the ability to differentiate into the cells of all three germ layers both in vitro and in vivo. To examine whether hESC lines derived from two developmental stages of the embryo differ in gene expression, we have subjected three blastomere derived hESC lines and two ICM-derived hESC lines grown under identical culture conditions to transcriptome analysis using gene expression arrays. Unlike previously reported comparisons of hESC lines which demonstrated, apart from core hESC-associated pluripotency signature, significant variations in gene expression profiles of different lines, our data show that hESC lines derived and grown under well-controlled defined culture conditions adopt nearly identical gene expression profiles. Moreover, blastomere-derived and ICM-derived hESC exhibited very similar transcriptional profiles independent of the developmental stage of the embryo from which they originated. Furthermore, this profile was evident in very early passages of the cells and did not appear to be affected by extensive passaging. These results suggest that during derivation process cells which give rise to hESC acquire virtually identical stable phenotype and are not affected by the developmental stage of the starting cell population. PMID- 22039510 TI - Development of a middle cerebral artery occlusion model in the nonhuman primate and a safety study of i.v. infusion of human mesenchymal stem cells. AB - BACKGROUND: Most experimental stroke research is carried out in rodents, but given differences between rodents and human, nonhuman primate (NHP) models may provide a valuable tool to study therapeutic interventions. The authors developed a surgical method for transient occlusion of the M1 branch of middle cerebral artery (MCA) in the African green monkey to evaluate safety aspects of intravenous infusion of mesenchymal stem cells (hMSCs) derived from human bone marrow. METHODS: The left Sylvian fissure was exposed by a small fronto-temporal craniotomy. The M1 branch of the MCA was exposed by microsurgical dissection and clipped for 2 to 4 hours. Neurological examinations and magnetic resonance imaging (MRI) were carried out at regular post-operative course. hMSCs were infused 1 hour after reperfusion (clip release) in the 3-hour occlusion model. RESULTS: During M1 occlusion, two patterns of changes were observed in the lateral hemisphere surface. One pattern (Pattern 1) was darkening of venous blood, small vessel collapse, and blood pooling with no venous return in cortical veins. Animals with these three features had severe and lasting hemiplegia and MRI demonstrated extensive MCA territory infarction. Animals in the second pattern (Pattern 2) displayed darkening of venous blood, small vessel collapse, and reduced but incompletely occluded venous flow and the functional deficit was much less severe and MRI indicated smaller infarction areas in brain. The severe group (Pattern 1) likely had less extensive collateral circulation than the less severe group (Pattern 2) where venous pooling of blood was not observed. The hMSC infused animals showed a trend for greater functional improvement that was not statistically significant in the acute phase and no additive negative effects. CONCLUSIONS: These results indicate inter-animal variability of collateral circulation after complete M1 occlusion and that hMSC infusion is safe in the developed NHP stroke model. PMID- 22039511 TI - Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala. AB - Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment. PMID- 22039512 TI - Efficient construction of homozygous diploid strains identifies genes required for the hyper-filamentous phenotype in Saccharomyces cerevisiae. AB - Yeast cells undergo diploid-specific developments such as spore formation via meiosis and pseudohyphal development under certain nutrient-limited conditions. Studies on these aspects require homozygous diploid mutants, which are generally constructed by crossing strains of opposite mating-type with the same genetic mutation. So far, there has been no direct way to generate and select diploids from haploid cells. Here, we developed a method for efficient construction of homozygous diploids using a PGAL1-HO gene (galactose-inducible mating-type switch) and a PSTE18-URA3 gene (counter selection marker for diploids). Diploids are generated by transient induction of the HO endonuclease, which is followed by mating of part of the haploid population. Since the STE18 promoter is repressed in diploids, diploids carrying PSTE18-URA3 can be selected on 5-fluoroorotic acid (5-FOA) plates where the uracil prototrophic haploids cannot grow. To demonstrate that this method is useful for genetic studies, we screened suppressor mutations of the complex colony morphology, strong agar invasion and/or hyper-filamentous growth caused by lack of the Hog1 MAPK in the diploid Sigma1278b strain background. Following this approach, we identified 49 suppressor mutations. Those include well-known positive regulator genes for filamentous growth signaling pathways, genes involved in mitochondrial function, DNA damage checkpoint, chromatin remodeling, and cell cycle, and also previously uncharacterized genes. Our results indicate that combinatorial use of the PGAL1-HO and PSTE18-URA3 genes is suitable to efficiently construct and select diploids and that this approach is useful for genetic studies especially when combined with large-scale screening. PMID- 22039513 TI - Targeted deletion of Nrf2 reduces urethane-induced lung tumor development in mice. AB - Nrf2 is a key transcription factor that regulates cellular redox and defense responses. However, permanent Nrf2 activation in human lung carcinomas promotes pulmonary malignancy and chemoresistance. We tested the hypothesis that Nrf2 has cell survival properties and lack of Nrf2 suppresses chemically-induced pulmonary neoplasia by treating Nrf2(+/+) and Nrf2(-/-) mice with urethane. Airway inflammation and injury were assessed by bronchoalveolar lavage analyses and histopathology, and lung tumors were analyzed by gross and histologic analysis. We used transcriptomics to assess Nrf2-dependent changes in pulmonary gene transcripts at multiple stages of neoplasia. Lung hyperpermeability, cell death and apoptosis, and inflammatory cell infiltration were significantly higher in Nrf2(-/-) mice compared to Nrf2(+/+) mice 9 and 11 wk after urethane. Significantly fewer lung adenomas were found in Nrf2(-/-) mice than in Nrf2(+/+) mice at 12 and 22 wk. Nrf2 modulated expression of genes involved cell-cell signaling, glutathione metabolism and oxidative stress response, and immune responses during early stage neoplasia. In lung tumors, Nrf2-altered genes had roles in transcriptional regulation of cell cycle and proliferation, carcinogenesis, organismal injury and abnormalities, xenobiotic metabolism, and cell-cell signaling genes. Collectively, Nrf2 deficiency decreased susceptibility to urethane-induced lung tumorigenesis in mice. Cell survival properties of Nrf2 were supported, at least in part, by reduced early death of initiated cells and heightened advantage for tumor cell expansion in Nrf2(+/+) mice relative to Nrf2( /-) mice. Our results were consistent with the concept that Nrf2 over-activation is an adaptive response of cancer conferring resistance to anti-cancer drugs and promoting malignancy. PMID- 22039514 TI - Tau enhances alpha-synuclein aggregation and toxicity in cellular models of synucleinopathy. AB - BACKGROUND: The simultaneous accumulation of different misfolded proteins in the central nervous system is a common feature in many neurodegenerative diseases. In most cases, co-occurrence of abnormal deposited proteins is observed in different brain regions and cell populations, but, in some instances, the proteins can be found in the same cellular aggregates. Co-occurrence of tau and alpha-synuclein (alpha-syn) aggregates has been described in neurodegenerative disorders with primary deposition of alpha-syn, such as Parkinson's disease and dementia with Lewy bodies. Although it is known that tau and alpha-syn have pathological synergistic effects on their mutual fibrillization, the underlying biological effects remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: We used different cell models of synucleinopathy to investigate the effects of tau on alpha-syn aggregation. Using confocal microscopy and FRET-based techniques we observed that tau colocalized and interacted with alpha-syn aggregates. We also found that tau overexpression changed the pattern of alpha-syn aggregation, reducing the size and increasing the number of aggregates. This shift was accompanied by an increase in the levels of insoluble alpha-syn. Furthermore, co-transfection of tau increased secreted alpha-syn and cytotoxicity. CONCLUSIONS/SIGNIFICANCE: Our data suggest that tau enhances alpha-syn aggregation and toxicity and disrupts alpha-syn inclusion formation. This pathological synergistic effect between tau and alpha-syn may amplify the deleterious process and spread the damage in neurodegenerative diseases that show co-occurrence of both pathologies. PMID- 22039515 TI - Direct evidence for the co-expression of URP and GnRH in a sub-population of rat hypothalamic neurones: anatomical and functional correlation. AB - Urotensin-II-related peptide (URP) is an eight amino-acid neuropeptide recently isolated from rat brain and considered as the endogenous ligand for the GPR14 receptor. Using single and double immunohistochemical labelling, in situ hybridization and ultrastructural immunocytochemistry, we explored the cellular and subcellular localization of URP in the male rat brain. URP peptide was detected in numerous varicose fibres of the median eminence (ME) and organum vasculosum laminae terminalis (OVLT) as well as in neuronal cell bodies of the medial septal nucleus and diagonal band of Broca where corresponding mRNA were also detected. Combining in situ hybridization with immunohistochemistry, we showed that cell bodies of the rat anterior hypothalamus contained both URP mRNA and GnRH peptide. In addition, double ultrastructural immunodetection of URP and GnRH peptides clearly revealed, in the median eminence, the co-localization of both peptides in the same neuronal processes in the vicinity of fenestrated portal vessels. This remarkable cellular and subcellular distribution led us to test the effect of URP on the GnRH-induced gonadotrophins release in the anterior pituitary, and to discuss its putative role at the level of the median eminence. PMID- 22039516 TI - Notch activation by phenethyl isothiocyanate attenuates its inhibitory effect on prostate cancer cell migration. AB - Phenethyl isothiocyanate (PEITC) is a promising cancer chemopreventive component of edible cruciferous vegetables with in vivo efficacy against prostate cancer in experimental rodents. Cancer chemopreventive response to PEITC is characterized by its ability to inhibit multiple oncogenic signaling pathways, including nuclear factor-kappaB, Akt, and androgen receptor. The present study demonstrates, for the first time, that PEITC treatment activates Notch signaling in malignant as well as normal human prostate cells. Exposure of human prostate cancer cells (LNCaP, PC-3, and DU145) and a normal human prostate epithelial cell line (PrEC) to PEITC resulted in cleavage (active form) of Notch1 and Notch2, and increased transcriptional activity of Notch. In PC-3 and LNCaP cells, PEITC treatment caused induction of Notch ligands Jagged1 and Jagged2 (PC-3), overexpression of gamma-secretase complex components Presenilin1 and Nicastrin (PC-3), nuclear enrichment of cleaved Notch2, and/or up-regulation of Notch1, Notch2, Jagged1, and/or Jagged2 mRNA. PEITC-induced apoptosis in LNCaP and PC-3 cells was significantly attenuated by RNA interference of Notch2, but not by pharmacological inhibition of Notch1. Inhibition of PC-3 and LNCaP cell migration resulting from PEITC exposure was significantly augmented by knockdown of Notch2 protein as well as pharmacological inhibition of Notch1 activation. Nuclear expression of cleaved Notch2 protein was significantly higher in PC-3 xenografts from PEITC-treated mice and dorsolateral prostates from PEITC-fed TRAMP mice compared with respective control. Because Notch signaling is implicated in epithelial-mesenchymal transition and metastasis, the present study suggests that anti-metastatic effect of PEITC may be augmented by a combination regimen involving a Notch inhibitor. PMID- 22039517 TI - Comparing the usefulness of distance, monophyly and character-based DNA barcoding methods in species identification: a case study of neogastropoda. AB - BACKGROUND: DNA barcoding has recently been proposed as a promising tool for the rapid species identification in a wide range of animal taxa. Two broad methods (distance and monophyly-based methods) have been used. One method is based on degree of DNA sequence variation within and between species while another method requires the recovery of species as discrete clades (monophyly) on a phylogenetic tree. Nevertheless, some issues complicate the use of both methods. A recently applied new technique, the character-based DNA barcode method, however, characterizes species through a unique combination of diagnostic characters. METHODOLOGY/PRINCIPAL FINDINGS: Here we analyzed 108 COI and 102 16S rDNA sequences of 40 species of Neogastropoda from a wide phylogenetic range to assess the performance of distance, monophyly and character-based methods of DNA barcoding. The distance-based method for both COI and 16S rDNA genes performed poorly in terms of species identification. Obvious overlap between intraspecific and interspecific divergences for both genes was found. The "10* rule" threshold resulted in lumping about half of distinct species for both genes. The neighbour joining phylogenetic tree of COI could distinguish all species studied. However, the 16S rDNA tree could not distinguish some closely related species. In contrast, the character-based barcode method for both genes successfully identified 100% of the neogastropod species included, and performed well in discriminating neogastropod genera. CONCLUSIONS/SIGNIFICANCE: This present study demonstrates the effectiveness of the character-based barcoding method for species identification in different taxonomic levels, especially for discriminating the closely related species. While distance and monophyly-based methods commonly use COI as the ideal gene for barcoding, the character-based approach can perform well for species identification using relatively conserved gene markers (e.g., 16S rDNA in this study). Nevertheless, distance and monophyly based methods, especially the monophyly-based method, can still be used to flag species. PMID- 22039518 TI - Sleep loss reduces the DNA-binding of BMAL1, CLOCK, and NPAS2 to specific clock genes in the mouse cerebral cortex. AB - We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA binding of CLOCK and BMAL1 to target clock genes changes in function of time-of day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), 6, -12, and -18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and -6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven. PMID- 22039519 TI - Endo-lysosomal vesicles positive for Rab7 and LAMP1 are terminal vesicles for the transport of dextran. AB - The endo-lysosomal pathway is essential for intracellular transport and the degradation of extracellular cargo. The relationship between three populations of endo-lysosomal vesicles--Rab7-positive, LAMP1-positive, and both Rab7- and LAMP1 postive--was probed with fluorescence microscopy and single particle tracking. Of specific interest was determining if these vesicles were intermediate or terminal vesicles in the transport of extracellular cargo. We find that the major organelle in the endo-lysosomal pathway, both in terms of population and cargo transport, is positive for Rab7 and LAMP1. Dextran, a fluid phase cargo, shifts from localization within all three populations of vesicles at 30 minutes and 1 hour to primarily LAMP1- and Rab7/LAMP1-vesicles at longer times. This demonstrates that LAMP1- and Rab7/LAMP1-vesicles are terminal vesicles in the endo-lysosomal pathway. We tested two possible mechanisms for this distribution of cargo, delivery to mannose 6-phosphate receptor (M6PR)-negative vesicles and the fusion dynamics of individual vesicles. We find no correlation with M6PR but do find that Rab7-vesicles undergo significantly fewer fusion events than LAMP1- or Rab7/LAMP1-vesicles suggesting that the distribution of fluid phase cargo is driven by vesicle dynamics. PMID- 22039520 TI - LL37 and cationic peptides enhance TLR3 signaling by viral double-stranded RNAs. AB - BACKGROUND: Toll-like Receptor 3 (TLR3) detects viral dsRNA during viral infection. However, most natural viral dsRNAs are poor activators of TLR3 in cell based systems, leading us to hypothesize that TLR3 needs additional factors to be activated by viral dsRNAs. The anti-microbial peptide LL37 is the only known human member of the cathelicidin family of anti-microbial peptides. LL37 complexes with bacterial lipopolysaccharide (LPS) to prevent activation of TLR4, binds to ssDNA to modulate TLR9 and ssRNA to modulate TLR7 and 8. It synergizes with TLR2/1, TLR3 and TLR5 agonists to increase IL8 and IL6 production. This work seeks to determine whether LL37 enhances viral dsRNA recognition by TLR3. METHODOLOGY/PRINCIPAL FINDINGS: Using a human bronchial epithelial cell line (BEAS2B) and human embryonic kidney cells (HEK 293T) transiently transfected with TLR3, we found that LL37 enhanced poly(I:C)-induced TLR3 signaling and enabled the recognition of viral dsRNAs by TLR3. The presence of LL37 also increased the cytokine response to rhinovirus infection in BEAS2B cells and in activated human peripheral blood mononuclear cells. Confocal microscopy determined that LL37 could co-localize with TLR3. Electron microscopy showed that LL37 and poly(I:C) individually formed globular structures, but a complex of the two formed filamentous structures. To separate the effects of LL37 on TLR3 and TLR4, other peptides that bind RNA and transport the complex into cells were tested and found to activate TLR3 signaling in response to dsRNAs, but had no effect on TLR4 signaling. This is the first demonstration that LL37 and other RNA-binding peptides with cell penetrating motifs can activate TLR3 signaling and facilitate the recognition of viral ligands. CONCLUSIONS/SIGNIFICANCE: LL37 and several cell penetrating peptides can enhance signaling by TLR3 and enable TLR3 to respond to viral dsRNA. PMID- 22039521 TI - Lipoprotein lipase inhibits hepatitis C virus (HCV) infection by blocking virus cell entry. AB - A distinctive feature of HCV is that its life cycle depends on lipoprotein metabolism. Viral morphogenesis and secretion follow the very low-density lipoprotein (VLDL) biogenesis pathway and, consequently, infectious HCV in the serum is associated with triglyceride-rich lipoproteins (TRL). Lipoprotein lipase (LPL) hydrolyzes TRL within chylomicrons and VLDL but, independently of its catalytic activity, it has a bridging activity, mediating the hepatic uptake of chylomicrons and VLDL remnants. We previously showed that exogenously added LPL increases HCV binding to hepatoma cells by acting as a bridge between virus associated lipoproteins and cell surface heparan sulfate, while simultaneously decreasing infection levels. We show here that LPL efficiently inhibits cell infection with two HCV strains produced in hepatoma cells or in primary human hepatocytes transplanted into uPA-SCID mice with fully functional human ApoB lipoprotein profiles. Viruses produced in vitro or in vivo were separated on iodixanol gradients into low and higher density populations, and the infection of Huh 7.5 cells by both virus populations was inhibited by LPL. The effect of LPL depended on its enzymatic activity. However, the lipase inhibitor tetrahydrolipstatin restored only a minor part of HCV infectivity, suggesting an important role of the LPL bridging function in the inhibition of infection. We followed HCV cell entry by immunoelectron microscopy with anti-envelope and anti core antibodies. These analyses demonstrated the internalization of virus particles into hepatoma cells and their presence in intracellular vesicles and associated with lipid droplets. In the presence of LPL, HCV was retained at the cell surface. We conclude that LPL efficiently inhibits HCV infection by acting on TRL associated with HCV particles through mechanisms involving its lipolytic function, but mostly its bridging function. These mechanisms lead to immobilization of the virus at the cell surface. HCV-associated lipoproteins may therefore be a promising target for the development of new therapeutic approaches. PMID- 22039522 TI - Alcohol dysregulates corticotropin-releasing-hormone (CRH) promoter activity by interfering with the negative glucocorticoid response element (nGRE). AB - EtOH exposure in male rats increases corticotropin-releasing hormone (CRH) mRNA in the paraventricular nucleus of the hypothalamus (PVN), a brain region responsible for coordinating stress and anxiety responses. In this study we identified the molecular mechanisms involved in mediating these effects by examining the direct effects of EtOH on CRH promoter activity in a neuronal cell line derived from the PVN (IVB). In addition, we investigated the potential interactions of EtOH and glucocorticoids on the CRH promoter by concomitantly treating cells with EtOH and the glucocorticoid receptor (GR) antagonist RU486, and by sequentially deleting GR binding sites within glucocorticoid response element (GRE) on the CRH promoter. Cells were transiently transfected with a firefly luciferase reporter construct containing 2.5 kb of the rat wild type (WT) or mutated CRH promoter. Our results showed that EtOH treatment induced a biphasic response in CRH promoter activity. EtOH exposure for 0.5 h significantly decreased promoter activity compared to vehicle treated controls, whereas promoter activity was significantly increased after 2.0 h of EtOH exposure. Treatment with RU486, or deletion of the GR binding sites 1 and 2 within the GRE, abolished the EtOH-induced increase in the promoter activity, however did not affect EtOH-induced decrease in CRH promoter activity at an earlier time point. Overall, our data suggest that alcohol exposure directly regulates CRH promoter activity by interfering with the normal feedback mechanisms of glucocorticoids mediated by GR signaling at the GRE site of the CRH promoter. PMID- 22039523 TI - piggyBac transposon somatic mutagenesis with an activated reporter and tracker (PB-SMART) for genetic screens in mice. AB - Somatic forward genetic screens have the power to interrogate thousands of genes in a single animal. Retroviral and transposon mutagenesis systems in mice have been designed and deployed in somatic tissues for surveying hematopoietic and solid tumor formation. In the context of cancer, the ability to visually mark mutant cells would present tremendous advantages for identifying tumor formation, monitoring tumor growth over time, and tracking tumor infiltrations and metastases into wild-type tissues. Furthermore, locating mutant clones is a prerequisite for screening and analyzing most other somatic phenotypes. For this purpose, we developed a system using the piggyBac (PB) transposon for somatic mutagenesis with an activated reporter and tracker, called PB-SMART. The PB-SMART mouse genetic screening system can simultaneously induce somatic mutations and mark mutated cells using bioluminescence or fluorescence. The marking of mutant cells enable analyses that are not possible with current somatic mutagenesis systems, such as tracking cell proliferation and tumor growth, detecting tumor cell infiltrations, and reporting tissue mutagenesis levels by a simple ex vivo visual readout. We demonstrate that PB-SMART is highly mutagenic, capable of tumor induction with low copy transposons, which facilitates the mapping and identification of causative insertions. We further integrated a conditional transposase with the PB-SMART system, permitting tissue-specific mutagenesis with a single cross to any available Cre line. Targeting the germline, the system could also be used to conduct F1 screens. With these features, PB-SMART provides an integrated platform for individual investigators to harness the power of somatic mutagenesis and phenotypic screens to decipher the genetic basis of mammalian biology and disease. PMID- 22039524 TI - Violating social norms when choosing friends: how rule-breakers affect social networks. AB - Social networks rely on basic rules of conduct to yield functioning societies in both human and animal populations. As individuals follow established rules, their behavioral decisions shape the social network and give it structure. Using dynamic, self-organizing social network models we demonstrate that defying conventions in a social system can affect multiple levels of social and organizational success independently. Such actions primarily affect actors' own positions within the network, but individuals can also affect the overall structure of a network even without immediately affecting themselves or others. These results indicate that defying the established social norms can help individuals to change the properties of a social system via seemingly neutral behaviors, highlighting the power of rule-breaking behavior to transform convention-based societies, even before direct impacts on individuals can be measured. PMID- 22039525 TI - Thrombospondin1 deficiency reduces obesity-associated inflammation and improves insulin sensitivity in a diet-induced obese mouse model. AB - BACKGROUND: Obesity is prevalent worldwide and is associated with insulin resistance. Advanced studies suggest that obesity-associated low-grade chronic inflammation contributes to the development of insulin resistance and other metabolic complications. Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix protein that is up-regulated in inflamed adipose tissue. A recent study suggests a positive correlation of TSP1 with obesity, adipose inflammation, and insulin resistance. However, the direct effect of TSP1 on obesity and insulin resistance is not known. Therefore, we investigated the role of TSP1 in mediating obesity-associated inflammation and insulin resistance by using TSP1 knockout mice. METHODOLOGY/PRINCIPAL FINDINGS: Male TSP1-/- mice and wild type littermate controls were fed a low-fat (LF) or a high-fat (HF) diet for 16 weeks. Throughout the study, body weight and fat mass increased similarly between the TSP1-/- mice and WT mice under HF feeding conditions, suggesting that TSP1 deficiency does not affect the development of obesity. However, obese TSP1-/ mice had improved glucose tolerance and increased insulin sensitivity compared to the obese wild type mice. Macrophage accumulation and inflammatory cytokine expression in adipose tissue were reduced in obese TSP1-/- mice. Consistent with the local decrease in pro-inflammatory cytokine levels, systemic inflammation was also decreased in the obese TSP1-/- mice. Furthermore, in vitro data demonstrated that TSP1 deficient macrophages had decreased mobility and a reduced inflammatory phenotype. CONCLUSION: TSP1 deficiency did not affect the development of high-fat diet induced obesity. However, TSP1 deficiency reduced macrophage accumulation in adipose tissue and protected against obesity related inflammation and insulin resistance. Our data demonstrate that TSP1 may play an important role in regulating macrophage function and mediating obesity-induced inflammation and insulin resistance. These data suggest that TSP1 may serve as a potential therapeutic target to improve the inflammatory and metabolic complications of obesity. PMID- 22039526 TI - Fractalkine expression induces endothelial progenitor cell lysis by natural killer cells. AB - BACKGROUND: Circulating CD34(+) cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis. We hypothesized that cell surface expression of the chemokine fractalkine (FKN) could target progenitor cell injury by Natural Killer (NK) cells, thereby limiting their availability for vascular repair. METHODOLOGY/PRINCIPAL FINDINGS: We show that CD34(+)-derived Endothelial Colony Forming Cells (ECFC) can express FKN in response to TNF-alpha and IFN-gamma inflammatory cytokines and that FKN expression by ECFC stimulates NK cell adhesion, NK cell-mediated ECFC lysis and microparticles release in vitro. The specific involvement of membrane FKN in these processes was demonstrated using FKN-transfected ECFC and anti-FKN blocking antibody. FKN expression was also evidenced on circulating CD34(+) progenitor cells and was detected at higher frequency in kidney transplant recipients, when compared to healthy controls. The proportion of CD34(+) cells expressing FKN was identified as an independent variable inversely correlated to CD34(+) progenitor cell count. We further showed that treatment of CD34(+) circulating cells isolated from adult blood donors with transplant serum or TNF-alpha/IFN-gamma can induce FKN expression. CONCLUSIONS: Our data highlights a novel mechanism by which FKN expression on CD34(+) progenitor cells may target their NK cell mediated killing and participate to their immune depletion in transplant recipients. Considering the numerous diseased contexts shown to promote FKN expression, our data identify FKN as a hallmark of altered progenitor cell homeostasis with potential implications in better evaluation of vascular repair in patients. PMID- 22039527 TI - Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice. AB - Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP) dynamics immediately following status epilepticus (SE) in mice. SE was induced by intraperitoneal (i.p.) injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+) imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV). No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst) firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP), was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP)-induced Ca(2+) signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+) and K(+) current components. PMID- 22039528 TI - Picomolar dichotomous activity of gnidimacrin against HIV-1. AB - Highly active antiretroviral therapy (HAART) has offered a promising approach for controlling HIV-1 replication in infected individuals. However, with HARRT, HIV-1 is suppressed rather than eradicated due to persistence of HIV-1 in latent viral reservoirs. Thus, purging the virus from latent reservoirs is an important strategy toward eradicating HIV-1 infection. In this study, we discovered that the daphnane diterpene gnidimacrin, which was previously reported to have potent anti-cancer cell activity, activated HIV-1 replication and killed persistently infected cells at picomolar concentrations. In addition to its potential to purge HIV-1 from latently infected cells, gnidimacrin potently inhibited a panel of HIV 1 R5 virus infection of peripheral blood mononuclear cells (PBMCs) at an average concentration lower than 10 pM. In contrast, gnidimacrin only partially inhibited HIV-1 *4 virus infection of PBMCs. The strong anti-HIV-1 R5 virus activity of gnidimacrin was correlated with its effect on down-regulation of the HIV-1 coreceptor CCR5. The anti-R5 virus activity of gnidimacrin was completely abrogated by a selective protein kinase C beta inhibitor enzastaurin, which suggests that protein kinase C beta plays a key role in the potent anti-HIV-1 activity of gnidimacrin in PBMCs. In summary, these results suggest that gnidimacrin could activate latent HIV-1, specifically kill HIV-1 persistently infected cells, and inhibit R5 viruses at picomolar concentrations. PMID- 22039529 TI - Weighted correlation network analysis (WGCNA) applied to the tomato fruit metabolome. AB - BACKGROUND: Advances in "omics" technologies have revolutionized the collection of biological data. A matching revolution in our understanding of biological systems, however, will only be realized when similar advances are made in informatic analysis of the resulting "big data." Here, we compare the capabilities of three conventional and novel statistical approaches to summarize and decipher the tomato metabolome. METHODOLOGY: Principal component analysis (PCA), batch learning self-organizing maps (BL-SOM) and weighted gene co expression network analysis (WGCNA) were applied to a multivariate NMR dataset collected from developmentally staged tomato fruits belonging to several genotypes. While PCA and BL-SOM are appropriate and commonly used methods, WGCNA holds several advantages in the analysis of highly multivariate, complex data. CONCLUSIONS: PCA separated the two major genetic backgrounds (AC and NC), but provided little further information. Both BL-SOM and WGCNA clustered metabolites by expression, but WGCNA additionally defined "modules" of co-expressed metabolites explicitly and provided additional network statistics that described the systems properties of the tomato metabolic network. Our first application of WGCNA to tomato metabolomics data identified three major modules of metabolites that were associated with ripening-related traits and genetic background. PMID- 22039530 TI - Amphidromy links a newly documented fish community of continental Australian streams, to oceanic islands of the west Pacific. AB - BACKGROUND: Indo-Pacific high island streams experience extreme hydrological variation, and are characterised by freshwater fish species with an amphidromous life history. Amphidromy is a likely adaptation for colonisation of island streams following stochastic events that lead to local extirpation. In the Wet Tropics of north-eastern Australia, steep coastal mountain streams share similar physical characteristics to island systems. These streams are poorly surveyed, but may provide suitable habitat for amphidromous species. However, due to their ephemeral nature, common non-diadromous freshwater species of continental Australia are unlikely to persist. Consequently, we hypothesise that coastal Wet Tropics streams are faunally more similar, to distant Pacific island communities, than to nearby faunas of large continental rivers. METHODS/PRINCIPAL FINDINGS: Surveys of coastal Wet Tropics streams recorded 26 species, 10 of which are first records for Australia, with three species undescribed. This fish community is unique in an Australian context in that it contains mostly amphidromous species, including sicydiine gobies of the genera Sicyopterus, Sicyopus, Smilosicyopus and Stiphodon. Species presence/absence data of coastal Wet Tropics streams were compared to both Wet Tropics river networks and Pacific island faunas. ANOSIM indicated the fish fauna of north-eastern Australian coastal streams were more similar to distant Pacific islands (R = 0.76), than to nearby continental rivers (R = 0.98). MAIN CONCLUSIONS/SIGNIFICANCE: Coastal Wet Tropics streams are faunally more similar to distant Pacific islands (79% of species shared), than to nearby continental fauna due to two factors. First, coastal Wet Tropics streams lack many non-diadromous freshwater fish which are common in nearby large rivers. Second, many amphidromous species found in coastal Wet Tropics streams and Indo Pacific islands remain absent from large rivers of the Wet Tropics. The evolutionary and conservation significance of this newly discovered Australian fauna requires clarification in the context of the wider amphidromous fish community of the Pacific. PMID- 22039531 TI - Homeostatic proliferation and IL-7R alpha expression do not correlate with enhanced T cell proliferation and protection in chronic mouse malaria. AB - While chronic infection has been shown to enhance protection from disease caused by several pathogens, the mechanisms are not known. The gamma-c family of cytokines IL-7, IL-2, and IL-15 are implicated in homeostatic proliferation, which is thought to maintain T cell memory. However in chronic infection, prolonged antigen exposure itself may contribute to lymphocyte survival. We have previously observed that chronic malaria infection enhances protection to re infection, as well as enhancing B cell responses. Here, we show that chronic Plasmodium chabaudi malaria infection in mice enhances the expansion of CD4(+) T cells in a second infection, and that this correlates with increased expression of the IL-2/15 Receptor beta (CD122) on memory T cells, as well as increasing IL 2 producers on re-infection. IL-2 has been recently linked to improved secondary proliferation, while the role of IL-7 in maintenance of CD4(+) memory cells has been demonstrated in homeostatic proliferation, but its role in protective memory populations in infectious disease protective has not been fully investigated. Increased IL-7Ralpha (CD127) expression correlated, as previously reported with increased turnover of CD4 memory cells, however, this was not linked to protection or enhanced response to rechallenge, These data support the idea that antigen or IL-2 production resulting from chronic stimulation may play a role in an enhanced secondary T cell response. PMID- 22039532 TI - Differential responses of the coral host and their algal symbiont to thermal stress. AB - The success of any symbiosis under stress conditions is dependent upon the responses of both partners to that stress. The coral symbiosis is particularly susceptible to small increases of temperature above the long term summer maxima, which leads to the phenomenon known as coral bleaching, where the intracellular dinoflagellate symbionts are expelled. Here we for the first time used quantitative PCR to simultaneously examine the gene expression response of orthologs of the coral Acropora aspera and their dinoflagellate symbiont Symbiodinium. During an experimental bleaching event significant up-regulation of genes involved in stress response (HSP90 and HSP70) and carbon metabolism (glyceraldehyde-3-phosphate dehydrogenase, alpha-ketoglutarate dehydrogenase, glycogen synthase and glycogen phosphorylase) from the coral host were observed. In contrast in the symbiont, HSP90 expression decreased, while HSP70 levels were increased on only one day, and only the alpha-ketoglutarate dehydrogenase expression levels were found to increase. In addition the changes seen in expression patterns of the coral host were much larger, up to 10.5 fold, compared to the symbiont response, which in all cases was less than 2-fold. This targeted study of the expression of key metabolic and stress genes demonstrates that the response of the coral and their symbiont vary significantly, also a response in the host transcriptome was observed prior to what has previously been thought to be the temperatures at which thermal stress events occur. PMID- 22039533 TI - Effects of artesunate on parasite recrudescence and dormancy in the rodent malaria model Plasmodium vinckei. AB - Artemisinin (ART) is the recommended first line therapy for treating uncomplicated and drug-resistant Plasmodium falciparum, the most pathogenic form of malaria. However, treatment failure following ART monotherapy is not uncommon and resistance to this rapidly acting drug has been reported in the Thai Cambodian border. Recent in vitro studies have shown that following treatment with dihydroartemisinin (DHA), the development of ring-stage parasites is arrested for up to 20 days. These arrested (i.e. dormant) rings could be responsible for the recrudescence of infection that is observed following ART monotherapy. To develop a better understanding of the stage-specific effects of ART and determine if dormancy occurs in vivo, the ART derivative artesunate (AS) was used to treat mice infected with the synchronous rodent malaria parasites P. vinckei petteri (non-lethal) and P. v. vinckei (lethal). Results show that in both the non-lethal and lethal strains, ring-stage parasites are the least susceptible to treatment with AS and that the day of treatment has more of an impact on recrudescence than the total dose administered. Additionally, 24 hrs post-treatment with AS, dormant forms similar in morphology to those seen in vitro were observed. Finally, rate of recrudescence studies suggest that there is a positive correlation between the number of dormant parasites present and when recrudescence occurs in the vertebrate host. Collectively, these data suggest that dormancy occurs in vivo and contributes to recrudescence that is observed following AS treatment. It is possible that this may represent a novel mechanism of parasite survival following treatment with AS. PMID- 22039534 TI - Modulation of cardiac ryanodine receptor channels by alkaline earth cations. AB - Cardiac ryanodine receptor (RyR2) function is modulated by Ca(2+) and Mg(2+). To better characterize Ca(2+) and Mg(2+) binding sites involved in RyR2 regulation, the effects of cytosolic and luminal earth alkaline divalent cations (M(2+): Mg(2+), Ca(2+), Sr(2+), Ba(2+)) were studied on RyR2 from pig ventricle reconstituted in bilayers. RyR2 were activated by M(2+) binding to high affinity activating sites at the cytosolic channel surface, specific for Ca(2+) or Sr(2+). This activation was interfered by Mg(2+) and Ba(2+) acting at low affinity M(2+) unspecific binding sites. When testing the effects of luminal M(2+) as current carriers, all M(2+) increased maximal RyR2 open probability (compared to Cs(+)), suggesting the existence of low affinity activating M(2+)-unspecific sites at the luminal surface. Responses to M(2+) vary from channel to channel (heterogeneity). However, with luminal Ba(2+)or Mg(2+), RyR2 were less sensitive to cytosolic Ca(2+) and caffeine-mediated activation, openings were shorter and voltage dependence was more marked (compared to RyR2 with luminal Ca(2+)or Sr(2+)). Kinetics of RyR2 with mixtures of luminal Ba(2+)/Ca(2+) and additive action of luminal plus cytosolic Ba(2+) or Mg(2+) suggest luminal M(2+) differentially act on luminal sites rather than accessing cytosolic sites through the pore. This suggests the presence of additional luminal activating Ca(2+)/Sr(2+)-specific sites, which stabilize high P(o) mode (less voltage-dependent) and increase RyR2 sensitivity to cytosolic Ca(2+) activation. In summary, RyR2 luminal and cytosolic surfaces have at least two sets of M(2+) binding sites (specific for Ca(2+) and unspecific for Ca(2+)/Mg(2+)) that dynamically modulate channel activity and gating status, depending on SR voltage. PMID- 22039535 TI - Characterization of Brca2-deficient plants excludes the role of NHEJ and SSA in the meiotic chromosomal defect phenotype. AB - In somatic cells, three major pathways are involved in the repair of DNA double strand breaks (DBS): Non-Homologous End Joining (NHEJ), Single-Strand Annealing (SSA) and Homologous Recombination (HR). In somatic and meiotic HR, DNA DSB are 5' to 3' resected, producing long 3' single-stranded DNA extensions. Brca2 is essential to load the Rad51 recombinase onto these 3' overhangs. The resulting nucleofilament can thus invade a homologous DNA sequence to copy and restore the original genetic information. In Arabidopsis, the inactivation of Brca2 specifically during meiosis by an RNAi approach results in aberrant chromosome aggregates, chromosomal fragmentation and missegregation leading to a sterility phenotype. We had previously suggested that such chromosomal behaviour could be due to NHEJ. In this study, we show that knock-out plants affected in both BRCA2 genes show the same meiotic phenotype as the RNAi-inactivated plants. Moreover, it is demonstrated that during meiosis, neither NHEJ nor SSA compensate for HR deficiency in BRCA2-inactivated plants. The role of the plant-specific DNA Ligase6 is also excluded. The possible mechanism(s) involved in the formation of these aberrant chromosomal bridges in the absence of HR during meiosis are discussed. PMID- 22039536 TI - A thiopurine drug inhibits West Nile virus production in cell culture, but not in mice. AB - Many viruses within the Flavivirus genus cause significant disease in humans; however, effective antivirals against these viruses are not currently available. We have previously shown that a thiopurine drug, 6-methylmercaptopurine riboside (6MMPr), inhibits replication of distantly related viruses within the Flaviviridae family in cell culture, including bovine viral diarrhea virus and hepatitis C virus replicon. Here we further examined the potential antiviral effect of 6MMPr on several diverse flaviviruses. In cell culture, 6MMPr inhibited virus production of yellow fever virus, dengue virus-2 (DENV-2) and West Nile virus (WNV) in a dose-dependent manner, and DENV-2 was significantly more sensitive to 6MMPr treatment than WNV. We then explored the use of 6MMPr as an antiviral against WNV in an immunocompetent mouse model. Once a day treatment of mice with 0.5 mg 6MMPr was just below the toxic dose in our mouse model, and this dose was used in subsequent studies. Mice were treated with 6MMPr immediately after subcutaneous inoculation with WNV for eight consecutive days. Treatment with 6MMPr exacerbated weight loss in WNV-inoculated mice and did not significantly affect mortality. We hypothesized that 6MMPr has low bioavailability in the central nervous system (CNS) and examined the effect of pre-treatment with 6MMPr on viral loads in the periphery and CNS. Pre-treatment with 6MMPr had no significant effect on viremia or viral titers in the periphery, but resulted in significantly higher viral loads in the brain, suggesting that the effect of 6MMPr is tissue-dependent. In conclusion, despite being a potent inhibitor of flaviviruses in cell culture, 6MMPr was not effective against West Nile disease in mice; however, further studies are warranted to reduce the toxicity and/or improve the bioavailability of this potential antiviral drug. PMID- 22039537 TI - Electrical stimulation of the primate lateral habenula suppresses saccadic eye movement through a learning mechanism. AB - The lateral habenula (LHb) is a brain structure which represents negative motivational value. Neurons in the LHb are excited by unpleasant events such as reward omission and aversive stimuli, and transmit these signals to midbrain dopamine neurons which are involved in learning and motivation. However, it remains unclear whether these phasic changes in LHb neuronal activity actually influence animal behavior. To answer this question, we artificially activated the LHb by electrical stimulation while monkeys were performing a visually guided saccade task. In one block of trials, saccades to one fixed direction (e.g., right direction) were followed by electrical stimulation of the LHb while saccades to the other direction (e.g., left direction) were not. The direction stimulation contingency was reversed in the next block. We found that the post saccadic stimulation of the LHb increased the latencies of saccades in subsequent trials. Notably, the increase of the latency occurred gradually as the saccade was repeatedly followed by the stimulation, suggesting that the effect of the post-saccadic stimulation was accumulated across trials. LHb stimulation starting before saccades, on the other hand, had no effect on saccade latency. Together with previous studies showing LHb activation by reward omission and aversive stimuli, the present stimulation experiment suggests that LHb activity contributes to learning to suppress actions which lead to unpleasant events. PMID- 22039538 TI - CcpA ensures optimal metabolic fitness of Streptococcus pneumoniae. AB - In gram-positive bacteria, the transcriptional regulator CcpA is at the core of catabolite control mechanisms. In the human pathogen Streptococcus pneumoniae, links between CcpA and virulence have been established, but its role as a master regulator in different nutritional environments remains to be elucidated. Thus, we performed whole-transcriptome and metabolic analyses of S. pneumoniae D39 and its isogenic ccpA mutant during growth on glucose or galactose, rapidly and slowly metabolized carbohydrates presumably encountered by the bacterium in different host niches. CcpA affected the expression of up to 19% of the genome covering multiple cellular processes, including virulence, regulatory networks and central metabolism. Its prevalent function as a repressor was observed on glucose, but unexpectedly also on galactose. Carbohydrate-dependent CcpA regulation was also observed, as for the tagatose 6-phosphate pathway genes, which were activated by galactose and repressed by glucose. Metabolite analyses revealed that two pathways for galactose catabolism are functionally active, despite repression of the Leloir genes by CcpA. Surprisingly, galactose-induced mixed-acid fermentation apparently required CcpA, since genes involved in this type of metabolism were mostly under CcpA-repression. These findings indicate that the role of CcpA extends beyond transcriptional regulation, which seemingly is overlaid by other regulatory mechanisms. In agreement, CcpA influenced the level of many intracellular metabolites potentially involved in metabolic regulation. Our data strengthen the view that a true understanding of cell physiology demands thorough analyses at different cellular levels. Moreover, integration of transcriptional and metabolic data uncovered a link between CcpA and the association of surface molecules (e.g. capsule) to the cell wall. Hence, CcpA may play a key role in mediating the interaction of S. pneumoniae with its host. Overall, our results support the hypothesis that S. pneumoniae optimizes basic metabolic processes, likely enhancing in vivo fitness, in a CcpA-mediated manner. PMID- 22039540 TI - Development and characterization of microsatellite markers for the Cape gooseberry Physalis peruviana. AB - Physalis peruviana, commonly known as Cape gooseberry, is an Andean Solanaceae fruit with high nutritional value and interesting medicinal properties. In the present study we report the development and characterization of microsatellite loci from a P. peruviana commercial Colombian genotype. We identified 932 imperfect and 201 perfect Simple Sequence Repeats (SSR) loci in untranslated regions (UTRs) and 304 imperfect and 83 perfect SSR loci in coding regions from the assembled Physalis peruviana leaf transcriptome. The UTR SSR loci were used for the development of 162 primers for amplification. The efficiency of these primers was tested via PCR in a panel of seven P. peruviana accessions including Colombia, Kenya and Ecuador ecotypes and one closely related species Physalis floridana. We obtained an amplification rate of 83% and a polymorphic rate of 22%. Here we report the first P. peruviana specific microsatellite set, a valuable tool for a wide variety of applications, including functional diversity, conservation and improvement of the species. PMID- 22039539 TI - Patterns of predicted T-cell epitopes associated with antigenic drift in influenza H3N2 hemagglutinin. AB - Antigenic drift allowing escape from neutralizing antibodies is an important feature of transmission and survival of influenza viruses in host populations. Antigenic drift has been studied in particular detail for influenza A H3N2 and well defined antigenic clusters of this virus documented. We examine how host immunogenetics contributes to determination of the antibody spectrum, and hence the immune pressure bringing about antigenic drift. Using uTOPETM bioinformatics analysis of predicted MHC binding, based on amino acid physical property principal components, we examined the binding affinity of all 9-mer and 15-mer peptides within the hemagglutinin 1 (HA1) of 447 H3N2 virus isolates to 35 MHC-I and 14 MHC-II alleles. We provide a comprehensive map of predicted MHC-I and MHC II binding affinity for a broad array of HLA alleles for the H3N2 influenza HA1 protein. Each HLA allele exhibited a characteristic predicted binding pattern. Cluster analysis for each HLA allele shows that patterns based on predicted MHC binding mirror those described based on antibody binding. A single amino acid mutation or position displacement can result in a marked difference in MHC binding and hence potential T-helper function. We assessed the impact of individual amino acid changes in HA1 sequences between 10 virus isolates from 1968-2002, representative of antigenic clusters, to understand the changes in MHC binding over time. Gain and loss of predicted high affinity MHC-II binding sites with cluster transitions were documented. Predicted high affinity MHC-II binding sites were adjacent to antibody binding sites. We conclude that host MHC diversity may have a major determinant role in the antigenic drift of influenza A H3N2. PMID- 22039541 TI - Investigation by imaging mass spectrometry of biomarker candidates for aging in the hair cortex. AB - BACKGROUND: Human hair is one of the essential components that define appearance and is a useful source of samples for non-invasive biomonitoring. We describe a novel application of imaging mass spectrometry (IMS) of hair biomolecules for advanced molecular characterization and a better understanding of hair aging. As a cosmetic and biomedical application, molecules whose levels in hair altered with aging were comprehensively investigated. METHODS: Human hair was collected from 15 young (20+/-5 years old) and 15 older (50+/-5 years old) volunteers. Matrix-free laser desorption/ionization IMS was used to visualize molecular distribution in the hair sections. Hair-specific ions displaying a significant difference in the intensities between the 2 age groups were extracted as candidate markers for aging. Tissue localization of the molecules and alterations in their levels in the cortex and medulla in the young and old groups were determined. RESULTS: Among the 31 molecules detected specifically in hair sections, 2--one at m/z 153.00, tentatively assigned to be dihydrouracil, and the other at m/z 207.04, identified to be 3,4-dihydroxymandelic acid (DHMA)- exhibited a higher signal intensity in the young group than in the old, and 1 molecule at m/z 164.00, presumed to be O-phosphoethanolamine, displayed a higher intensity in the old group. Among the 3, putative O-phosphoethanolamine showed a cortex-specific distribution. The 3 molecules in cortex presented the same pattern of alteration in signal intensity with aging, whereas those in medulla did not exhibit significant alteration. CONCLUSION: Three molecules whose levels in hair altered with age were extracted. While they are all possible markers for aging, putative dihydrouracil and DHMA, are also suspected to play a role in maintaining hair properties and could be targets for cosmetic supplementation. Mapping of ion localization in hair by IMS is a powerful method to extract biomolecules in specified regions and determine their tissue distribution. PMID- 22039542 TI - Hypervirulent K. pneumoniae secretes more and more active iron-acquisition molecules than "classical" K. pneumoniae thereby enhancing its virulence. AB - BACKGROUND: A new hypervirulent (hypermucoviscous) clinical variant of Klebsiella pneumoniae (hvKP) has emerged over the last decade. Our goal is to identify new mechanisms, which increase the virulence hvKP compared to "classic" K. pneumoniae (cKP). METHODOLOGY/PRINCIPAL FINDINGS: Various growth assays were performed in human ascites, human serum, and laboratory medium with the hvKP strain hvKP1 (wt), randomly chosen blood isolates of cKP strains (cKP1-4), and mutant constructs deficient in the secretion of selected compounds. An in vivo mouse model that mimics infection due to hvKP and a quantitative siderophore assay were also used. It was established that a molecule(s)/factor(s) was secreted by hvKP1 significantly enhanced its growth and/or survival in human ascites. This molecule(s)/factor(s) also increased the growth and/or survival of hvKP1 in serum ex vivo and in an in vivo mouse model that measures metastatic spread after subcutaneous challenge, thereby further establishing biologic significance. Although features such as a size of <3kD, heat stability, and growth characteristics in ascites suggested this molecule(s) was a quorum-sensing compound, data presented demonstrates that this molecule(s)/factor(s) is involved in iron uptake and is likely a siderophore(s) or another iron-acquisition molecule. Although it is known that iron acquisition is critical for virulence, a novel aspect of this observation is that hvKP1 produces quantitatively more siderophores that appear to be biologically more active (increased affinity for iron or more resistant to host factors) than those produced by cKP strains. CONCLUSIONS/SIGNIFICANCE: The data presented delineates a new mechanism by which hvKP increases its pathogenic potential compared to cKP strains. This paradigm may be broadly applicable to other extraintestinal gram-negative bacilli. PMID- 22039543 TI - Functional redundancy patterns reveal non-random assembly rules in a species-rich marine assemblage. AB - The relationship between species and the functional diversity of assemblages is fundamental in ecology because it contains key information on functional redundancy, and functionally redundant ecosystems are thought to be more resilient, resistant and stable. However, this relationship is poorly understood and undocumented for species-rich coastal marine ecosystems. Here, we used underwater visual censuses to examine the patterns of functional redundancy for one of the most diverse vertebrate assemblages, the coral reef fishes of New Caledonia, South Pacific. First, we found that the relationship between functional and species diversity displayed a non-asymptotic power-shaped curve, implying that rare functions and species mainly occur in highly diverse assemblages. Second, we showed that the distribution of species amongst possible functions was significantly different from a random distribution up to a threshold of ~90 species/transect. Redundancy patterns for each function further revealed that some functions displayed fast rates of increase in redundancy at low species diversity, whereas others were only becoming redundant past a certain threshold. This suggested non-random assembly rules and the existence of some primordial functions that would need to be fulfilled in priority so that coral reef fish assemblages can gain a basic ecological structure. Last, we found little effect of habitat on the shape of the functional-species diversity relationship and on the redundancy of functions, although habitat is known to largely determine assemblage characteristics such as species composition, biomass, and abundance. Our study shows that low functional redundancy is characteristic of this highly diverse fish assemblage, and, therefore, that even species-rich ecosystems such as coral reefs may be vulnerable to the removal of a few keystone species. PMID- 22039544 TI - A highly stable plastidic-type ferredoxin-NADP(H) reductase in the pathogenic bacterium Leptospira interrogans. AB - Leptospira interrogans is a bacterium that is capable of infecting animals and humans, and its infection causes leptospirosis with a range of symptoms from flu like to severe illness and death. Despite being a bacteria, Leptospira interrogans contains a plastidic class ferredoxin-NADP(H) reductase (FNR) with high catalytic efficiency, at difference from the bacterial class FNRs. These flavoenzymes catalyze the electron transfer between NADP(H) and ferredoxins or flavodoxins. The inclusion of a plastidic FNR in Leptospira metabolism and in its parasitic life cycle is not currently understood. Bioinformatic analyses of the available genomic and proteins sequences showed that the presence of this enzyme in nonphotosynthetic bacteria is restricted to the Leptospira genus and that a [4Fe-4S] ferredoxin (LB107) encoded by the Leptospira genome may be the natural substrate of the enzyme. Leptospira FNR (LepFNR) displayed high diaphorase activity using artificial acceptors and functioned as a ferric reductase. LepFNR displayed cytochrome c reductase activity with the Leptospira LB107 ferredoxin with an optimum at pH 6.5. Structural stability analysis demonstrates that LepFNR is one of the most stable FNRs analyzed to date. The persistence of a native folded LepFNR structure was detected in up to 6 M urea, a condition in which the enzyme retains 38% activity. In silico analysis indicates that the high LepFNR stability might be due to robust interactions between the FAD and the NADP(+) domains of the protein. The limited bacterial distribution of plastidic class FNRs and the biochemical and structural properties of LepFNR emphasize the uniqueness of this enzyme in the Leptospira metabolism. Our studies show that in L. interrogans a plastidic-type FNR exchanges electrons with a bacterial-type ferredoxin, process which has not been previously observed in nature. PMID- 22039545 TI - Determination of the crystal structure and active residues of FabV, the enoyl-ACP reductase from Xanthomonas oryzae. AB - BACKGROUND: Enoyl-ACP reductase (ENR) catalyses the last reduction reaction in the fatty acid elongation cycle in bacteria and is a good antimicrobial target candidate. FabV is the most recently discovered class of ENR, but we lack information about the atomic structure and the key residues involved in reductase activity except for the known conserved tyrosine and lysine residues in the Y X(8)-K active site motif. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the crystal structure of FabV from Xanthomonas oryzae (xoFabV). The crystal structure of this enzyme has been solved to 1.6 A resolution in space group P2(1)2(1)2(1). The model of xoFabV consists of one monomer in the asymmetric unit which is composed of 13 alpha-helices and 11 beta-strands, representing a canonical Rossmann fold architecture. Structural comparison presents that the locations of the conserved tyrosine (Y236) and lysine (K245) residues in the Y-X(8)-K active site motif of xoFabV and the Y-X(6)-K motif of ecFabI are notably similar. However, the conformations of Y236 in xoFabV and Y156 in ecFabI are distinct. Structure-based site-directed mutagenesis and enzymatic activity assays reveal that in addition to the conserved Y236 and K245 in the Y-X(8)-K motif, Y53, D111 and Y226 are key residues implicated in the reductase activity, and F113 and T276 are also important for enzyme function. Moreover, a proposed active lysine located immediately after the Y-X(8)-K motif in FabV from Burkholderia mallei (bmFabV) is altered to an inactive V246 in xoFabV. CONCLUSIONS/SIGNIFICANCE: We determine the first crystal structure of the FabV enzyme and identify several residues important for its enzymatic activity. These findings lay a solid foundation for the development of specific antibacterial inhibitors of the pathogenic bacteria, such as Vibrio cholerae, Burkholderia species and Xanthomonas species. PMID- 22039546 TI - A comparison of parallel pyrosequencing and sanger clone-based sequencing and its impact on the characterization of the genetic diversity of HIV-1. AB - BACKGROUND: Pyrosequencing technology has the potential to rapidly sequence HIV-1 viral quasispecies without requiring the traditional approach of cloning. In this study, we investigated the utility of ultra-deep pyrosequencing to characterize genetic diversity of the HIV-1 gag quasispecies and assessed the possible contribution of pyrosequencing technology in studying HIV-1 biology and evolution. METHODOLOGY/PRINCIPAL FINDINGS: HIV-1 gag gene was amplified from 96 patients using nested PCR. The PCR products were cloned and sequenced using capillary based Sanger fluorescent dideoxy termination sequencing. The same PCR products were also directly sequenced using the 454 pyrosequencing technology. The two sequencing methods were evaluated for their ability to characterize quasispecies variation, and to reveal sites under host immune pressure for their putative functional significance. A total of 14,034 variations were identified by 454 pyrosequencing versus 3,632 variations by Sanger clone-based (SCB) sequencing. 11,050 of these variations were detected only by pyrosequencing. These undetected variations were located in the HIV-1 Gag region which is known to contain putative cytotoxic T lymphocyte (CTL) and neutralizing antibody epitopes, and sites related to virus assembly and packaging. Analysis of the positively selected sites derived by the two sequencing methods identified several differences. All of them were located within the CTL epitope regions. CONCLUSIONS/SIGNIFICANCE: Ultra-deep pyrosequencing has proven to be a powerful tool for characterization of HIV-1 genetic diversity with enhanced sensitivity, efficiency, and accuracy. It also improved reliability of downstream evolutionary and functional analysis of HIV-1 quasispecies. PMID- 22039547 TI - Biological responses to diesel exhaust particles (DEPs) depend on the physicochemical properties of the DEPs. AB - Diesel exhaust particles (DEPs) are the main components of ambient particulate materials, including polyaromatic hydrocarbons (PAHs), n-PAHs, heavy metals, and gaseous materials. Many epidemiological, clinical, and toxicological studies have shown that ambient particles, including DEPs, are associated with respiratory disorders, such as asthma, allergic rhinitis, and lung cancer. However, the relationship between the biological response to DEPs and their chemical composition remains unclear. In this study, we investigated the physicochemical properties of DEPs before toxicological studies, and then administered a single intratracheal instillation of DEPs to mice. The mice were then killed 1, 7, 14 and 28 days after DEP exposure to observe the biological responses induced by DEPs over time. Our findings suggest that DEPs engulfed into cells induced a Th2 type inflammatory response followed by DNA damage, whereas DEPs not engulfed into cells induced a Th1-type inflammatory response. Further, the physicochemical properties, including surface charge, particle size, and chemical composition, of DEPs play a crucial role in determining the biological responses to DEPs. Consequently, we suggest that the biological response to DEPs depend on cell particle interaction and the physicochemical properties of the particles. PMID- 22039548 TI - Action representation in patients with bilateral vestibular impairments. AB - During mental actions subjects feel themselves performing a movement without any corresponding motor output. Although broad information is available regarding the influence of central lesions on action representation, little is known about how peripheral damages affect mental events. In the current study, we investigated whether lack of vestibular information influences action representation. Twelve healthy adults and twelve patients with bilateral vestibular damage actually performed and mentally simulated walking and drawing. The locomotor paths implied one (first walking task) and four (second walking task) changes in the walking direction. In the drawing task, participants drew on a sheet of paper a path that was similar to that of the second walking task. We recorded and compared between the two groups the timing of actual and mental movements. We found significant temporal discrepancies between actual and mental walking movements in the group of patients. Conversely, drawing actual and drawing mental durations were similar. For the control group, an isochrony between mental and actual movements was observed for the three tasks. This result denotes an inconsistency between action representation and action execution following vestibular damage, which is specific to walking movements, and emphasizes the role of the vestibular system upon mental states of actions. This observation may have important clinical implications. During action planning vestibular patients may overestimate the capacity of their motor system (imaging faster, executing slower) with harmful consequences for their health. PMID- 22039549 TI - Identification of human NK17/NK1 cells. AB - BACKGROUND: Natural killer (NK) cells have both cytolytic and immunoregulatory functions. We recently described that these cells release the inflammatory cytokines IL-17 and IFN-gamma. However, the precise identity of the NK cell subset(s) that secrete these cytokines is not known. METHODOLOGY/PRINCIPAL FINDINGS: To isolate the cells secreting IL-17 and IFN-gamma, we took advantage of the findings that Th17/Th1 cells express chemokine receptors. Therefore, CD56(+)NK cells were stained with antibodies against various chemokine receptors and intracellularly with antibodies toward IL-17 and IFN-gamma. Consequently, we identified previously unrecognized subset of NK cells generated from normal human peripheral blood after activation with IL-2 but not PMA plus ionomycin. The cells are characterized by the expression of CD56(+) and CCR4(+), produce IL-17 and IFN gamma and are consequently named NK17/NK1 cells. They also express CD161, NKp30, NKp44, NKp46, NKG2D, CD158, CCL22, IL-2Rbeta and the common gamma chain but not CD127 or IL-23R. Further, they possess T-bet and RORgammat transcription factors. Antibodies to IL-1beta, IL-6, IL-21, or TGF-beta1 do not inhibit IL-2-induced generation of NK17/NK1 cells, suggesting that IL-2 has the capacity to polarize these cells. Notably, NK17/NK1 cells are abundant in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) without activation, and are generated from the peripheral blood of these patients after activation with IL-2. CONCLUSIONS/SIGNIFICANCE: NK17/NK1 cells identified here have not been previously described in healthy or MS patients. PMID- 22039550 TI - Misleading population estimates: biases and consistency of visual surveys and matrix modelling in the endangered bearded vulture. AB - Conservation strategies for long-lived vertebrates require accurate estimates of parameters relative to the populations' size, numbers of non-breeding individuals (the "cryptic" fraction of the population) and the age structure. Frequently, visual survey techniques are used to make these estimates but the accuracy of these approaches is questionable, mainly because of the existence of numerous potential biases. Here we compare data on population trends and age structure in a bearded vulture (Gypaetus barbatus) population from visual surveys performed at supplementary feeding stations with data derived from population matrix-modelling approximations. Our results suggest that visual surveys overestimate the number of immature (<2 years old) birds, whereas subadults (3-5 y.o.) and adults (>6 y.o.) were underestimated in comparison with the predictions of a population model using a stable-age distribution. In addition, we found that visual surveys did not provide conclusive information on true variations in the size of the focal population. Our results suggest that although long-term studies (i.e. population matrix modelling based on capture-recapture procedures) are a more time-consuming method, they provide more reliable and robust estimates of population parameters needed in designing and applying conservation strategies. The findings shown here are likely transferable to the management and conservation of other long-lived vertebrate populations that share similar life history traits and ecological requirements. PMID- 22039551 TI - Tyrosine deprotonation and associated hydrogen bond rearrangements in a photosynthetic reaction center. AB - Photosynthetic reaction centers from Blastochloris viridis possess Tyr-L162 located mid-way between the special pair chlorophyll (P) and the heme (heme3). While mutation of the tyrosine does not affect the kinetics of electron transfer from heme3 to P, recent time-resolved Laue diffraction studies reported displacement of Tyr-L162 in response to the formation of the photo-oxidized P(+*), implying a possible tyrosine deprotonation event. pK(a) values for Tyr L162 were calculated using the corresponding crystal structures. Movement of deprotonated Tyr-L162 toward Thr-M185 was observed in P(+*) formation. It was associated with rearrangement of the H-bond network that proceeds to P via Thr M185 and His-L168. PMID- 22039552 TI - Finnish Campylobacter jejuni strains of multilocus sequence type ST-22 complex have two lineages with different characteristics. AB - BACKGROUND: Campylobacter jejuni is the major cause of human bacterial gastroenteritis worldwide, and in a minority of cases, post-infectious complications may occur. ST-22 complex (usually Penner serotype 19) strains have been overrepresented among patients with postinfectious complications of campylobacteriosis. We here present a characterization of a collection of 27 Finnish C. jejuni strains of ST-22 complex, from humans (22 strains) and animal sources (five strains), with the aim of contributing to our knowledge of the pathogenesis of C. jejuni infections. METHODOLOGY/PRINCIPAL FINDINGS: All strains were analyzed by pulsed-field gel electrophoresis (PFGE) genotyping, lipo oligosaccharide (LOS) locus class, Y-glutamyl transpeptidase (GGT) activity, in vitro biofilm formation ability, invasion and adhesion in HeLa cells and induction of IL-8 production. ST-22 complex contained five STs (ST-22; ST-1947; ST-1966; ST-3892; ST-3996) which were homogeneous in having sialylated LOS class A(1) but on the other hand were distinguished into two major lineages according to the major STs (ST-22 and ST-1947) by different PFGE genotypes and certain other characteristics. All ST-22 strains had similar SmaI PFGE profiles, were GGT positive, and formed biofilms, except one strain, while ST-1947 strains were all GGT negative, did not form biofilm, had significantly higher motility than ST-22 (p<0.05) and had their SmaI PFGE profile. Invasion and adhesion as well as induction of IL-8 production on HeLa cells were strain-dependent characteristics. CONCLUSIONS/SIGNIFICANCE: ST-22 complex strains, reveal potential for molecular mimicry in host interactions upon infection as they all express sialylated LOS class A(1). The two major STs, ST-22 and ST-1947 formed two homogeneous lineages, which differed from each other both phenotypically and genetically, suggesting that the strains may have evolved separately, perhaps by interacting with different spectra of hosts. Further studies are needed in order to understand if these two lineages are associated with different disease outcomes. PMID- 22039553 TI - The neglected tropical diseases of India and South Asia: review of their prevalence, distribution, and control or elimination. PMID- 22039554 TI - Congenital Chagas disease: recommendations for diagnosis, treatment and control of newborns, siblings and pregnant women. PMID- 22039555 TI - Spontaneous clearance of Mycobacterium ulcerans in a case of Buruli ulcer. PMID- 22039556 TI - Alternative oxidase mediates pathogen resistance in Paracoccidioides brasiliensis infection. AB - BACKGROUND: Paracoccidioides brasiliensis is a human thermal dimorphic pathogenic fungus. Survival of P. brasiliensis inside the host depends on the adaptation of this fungal pathogen to different conditions, namely oxidative stress imposed by immune cells. AIMS AND METHODOLOGY: In this study, we evaluated the role of alternative oxidase (AOX), an enzyme involved in the intracellular redox balancing, during host-P. brasiliensis interaction. We generated a mitotically stable P. brasiliensis AOX (PbAOX) antisense RNA (aRNA) strain with a 70% reduction in gene expression. We evaluated the relevance of PbAOX during interaction of conidia and yeast cells with IFN-gamma activated alveolar macrophages and in a mouse model of infection. Additionally, we determined the fungal cell's viability and PbAOX in the presence of H2O2. RESULTS: Interaction with IFN-gamma activated alveolar macrophages induced higher levels of PbAOX gene expression in PbWt conidia than PbWt yeast cells. PbAOX-aRNA conidia and yeast cells had decreased viability after interaction with macrophages. Moreover, in a mouse model of infection, we showed that absence of wild-type levels of PbAOX in P. brasiliensis results in a reduced fungal burden in lungs at weeks 8 and 24 post-challenge and an increased survival rate. In the presence of H2O2, we observed that PbWt yeast cells increased PbAOX expression and presented a higher viability in comparison with PbAOX-aRNA yeast cells. CONCLUSIONS: These data further support the hypothesis that PbAOX is important in the fungal defense against oxidative stress imposed by immune cells and is relevant in the virulence of P. brasiliensis. PMID- 22039557 TI - Rodent abundance dynamics and leptospirosis carriage in an area of hyper endemicity in New Caledonia. AB - BACKGROUND: Widespread but particularly incident in the tropics, leptospirosis is transmitted to humans directly or indirectly by virtually any Mammal species. However, rodents are recognized as the most important reservoir. In endemic regions, seasonal outbreaks are observed during hot rainy periods. In such regions, hot spots can be evidenced, where leptospirosis is "hyper-endemic", its incidence reaching 500 annual cases per 100,000. A better knowledge of how rodent populations and their Leptospira prevalence respond to seasonal and meteorological fluctuations might help implement relevant control measures. METHODOLOGY/PRINCIPAL FINDINGS: In two tribes in New Caledonia with hyper-endemic leptospirosis, rodent abundance and Leptospira prevalence was studied twice a year, in hot and cool seasons for two consecutive years. Highly contrasted meteorological situations, particularly rainfall intensities, were noted between the two hot seasons studied. Our results show that during a hot and rainy period, both the rodent populations and their Leptospira carriage were higher. This pattern was more salient in commensal rodents than in the sylvatic rats. CONCLUSIONS/SIGNIFICANCE: The dynamics of rodents and their Leptospira carriage changed during the survey, probably under the influence of meteorology. Rodents were both more numerous and more frequently carrying (therefore disseminating) leptospires during a hot rainy period, also corresponding to a flooding period with higher risks of human exposure to waters and watered soils. The outbreaks of leptospirosis in hyper-endemic areas could arise from meteorological conditions leading to both an increased risk of exposure of humans and an increased volume of the rodent reservoir. Rodent control measures would therefore be most effective during cool and dry seasons, when rodent populations and leptospirosis incidence are low. PMID- 22039558 TI - Post-treatment follow-up study of abdominal cystic echinococcosis in tibetan communities of northwest Sichuan Province, China. AB - BACKGROUND: Human cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, with the liver as the most frequently affected organ, is known to be highly endemic in Tibetan communities of northwest Sichuan Province. Antiparasitic treatment with albendazole remains the primary choice for the great majority of patients in this resource-poor remote area, though surgery is the most common approach for CE therapy that has the potential to remove cysts and lead to complete cure. The current prospective study aimed to assess the effectiveness of community based use of cyclic albendazole treatment in Tibetan CE cases, and concurrently monitor the changes of serum specific antibody levels during treatment. METHODOLOGY/PRINCIPAL FINDINGS: Ultrasonography was applied for diagnosis and follow-up of CE cases after cyclic albendazole treatment in Tibetan communities of Sichuan Province during 2006 to 2008, and serum specific IgG antibody levels against Echinococcus granulosus recombinant antigen B in ELISA was concurrently monitored in these cases. A total of 196 CE cases were identified by ultrasound, of which 37 (18.9%) showed evidence of spontaneous healing/involution of hepatic cyst(s) with CE4 or CE5 presentations. Of 49 enrolled CE cases for treatment follow-up, 32.7% (16) were considered to be cured based on B-ultrasound after 6 months to 30 months regular albendazole treatment, 49.0% (24) were improved, 14.3% (7) remained unchanged, and 4.1% (2) became aggravated. In general, patients with CE2 type cysts (daughter cysts present) needed a longer treatment course for cure (26.4 months), compared to cases with CE1 (univesicular cysts) (20.4 months) or CE3 type (detached cyst membrane or partial degeneration of daughter cysts) (9 months). In addition, the curative duration was longer in patients with large (>10 cm) cysts (22.3 months), compared to cases with medium (5-10 cm) cysts (17.3 months) or patients with small (<5 cm) cysts (6 months). At diagnosis, seven (53.8%) of 13 cases with CE1 type cysts without any previous intervention showed negative specific IgG antibody response to E. granulosus recombinant antigen B (rAgB). However, following 3 months to 18 months albendazole therapy, six of these 7 initially seronegative CE1 cases sero converted to be specific IgG antibody positive, and concurrently ultrasound scan showed that cysts changed to CE3a from CE1 type in all the six CE cases. Two major profiles of serum specific IgG antibody dynamics during albendazole treatment were apparent in CE cases: (i) presenting as initial elevation followed by subsequent decline, or (ii) a persistent decline. Despite a decline, however, specific antibody levels remained positive in most improved or cured CE cases. CONCLUSIONS: This was the first attempt to follow up community-screened cystic echinococcosis patients after albendazole therapy using ultrasonography and serology in an endemic Tibetan region. Cyclic albendazole treatment proved to be effective in the great majority of CE cases in this resource-poor area, but periodic abdominal ultrasound examination was necessary to guide appropriate treatment. Oral albendazole for over 18 months was more likely to result in CE cure. Poor drug compliance resulted in less good outcomes. Serology with recombinant antigen B could provide additional limited information about the effectiveness of albendazole in CE cases. Post-treatment positive specific IgG antibody seroconversion, in initially seronegative, CE1 patients was considered a good indication for positive therapeutic efficacy of albendazole. PMID- 22039559 TI - Hidden sylvatic foci of the main vector of Chagas disease Triatoma infestans: threats to the vector elimination campaign? AB - BACKGROUND: Establishing the sources of reinfestation after residual insecticide spraying is crucial for vector elimination programs. Triatoma infestans, traditionally considered to be limited to domestic or peridomestic (abbreviated as D/PD) habitats throughout most of its range, is the target of an elimination program that has achieved limited success in the Gran Chaco region in South America. METHODOLOGY/PRINCIPAL FINDINGS: During a two-year period we conducted semi-annual searches for triatomine bugs in every D/PD site and surrounding sylvatic habitats after full-coverage spraying of pyrethroid insecticides of all houses in a well-defined rural area in northwestern Argentina. We found six low density sylvatic foci with 24 T. infestans in fallen or standing trees located 110-2,300 m from the nearest house or infested D/PD site detected after insecticide spraying, when house infestations were rare. Analysis of two mitochondrial gene fragments of 20 sylvatic specimens confirmed their species identity as T. infestans and showed that their composite haplotypes were the same as or closely related to D/PD haplotypes. Population studies with 10 polymorphic microsatellite loci and wing geometric morphometry consistently indicated the occurrence of unrestricted gene flow between local D/PD and sylvatic populations. Mitochondrial DNA and microsatellite sibship analyses in the most abundant sylvatic colony revealed descendents from five different females. Spatial analysis showed a significant association between two sylvatic foci and the nearest D/PD bug population found before insecticide spraying. CONCLUSIONS: Our study shows that, despite of its high degree of domesticity, T. infestans has sylvatic colonies with normal chromatic characters (not melanic morphs) highly connected to D/PD conspecifics in the Argentinean Chaco. Sylvatic habitats may provide a transient or permanent refuge after control interventions, and function as sources for D/PD reinfestation. The occurrence of sylvatic foci of T. infestans in the Gran Chaco may pose additional threats to ongoing vector elimination efforts. PMID- 22039560 TI - Optimal timing of insecticide fogging to minimize dengue cases: modeling dengue transmission among various seasonalities and transmission intensities. AB - BACKGROUND: Dengue infection is endemic in many regions throughout the world. While insecticide fogging targeting the vector mosquito Aedes aegypti is a major control measure against dengue epidemics, the impact of this method remains controversial. A previous mathematical simulation study indicated that insecticide fogging minimized cases when conducted soon after peak disease prevalence, although the impact was minimal, possibly because seasonality and population immunity were not considered. Periodic outbreak patterns are also highly influenced by seasonal climatic conditions. Thus, these factors are important considerations when assessing the effect of vector control against dengue. We used mathematical simulations to identify the appropriate timing of insecticide fogging, considering seasonal change of vector populations, and to evaluate its impact on reducing dengue cases with various levels of transmission intensity. METHODOLOGY/PRINCIPAL FINDINGS: We created the Susceptible-Exposed Infectious-Recovered (SEIR) model of dengue virus transmission. Mosquito lifespan was assumed to change seasonally and the optimal timing of insecticide fogging to minimize dengue incidence under various lengths of the wet season was investigated. We also assessed whether insecticide fogging was equally effective at higher and lower endemic levels by running simulations over a 500-year period with various transmission intensities to produce an endemic state. In contrast to the previous study, the optimal application of insecticide fogging was between the onset of the wet season and the prevalence peak. Although it has less impact in areas that have higher endemicity and longer wet seasons, insecticide fogging can prevent a considerable number of dengue cases if applied at the optimal time. CONCLUSIONS/SIGNIFICANCE: The optimal timing of insecticide fogging and its impact on reducing dengue cases were greatly influenced by seasonality and the level of transmission intensity. We suggest that these factors should be considered when planning a control strategy against dengue vectors. PMID- 22039561 TI - Proteomic identification of IPSE/alpha-1 as a major hepatotoxin secreted by Schistosoma mansoni eggs. AB - BACKGROUND: Eggs deposited in the liver of the mammalian host by the blood fluke parasite, Schistosoma mansoni, normally drive a T-helper-2 (Th2)-mediated granulomatous response in immune-competent mice. By contrast, in mice deprived of T-cells and incapable of producing granulomata, egg-secreted proteins (ESP) induce acute hepatic injury and death. Previous work has shown that one such ESP, the T2 ribonuclease known as omega-1, is hepatotoxic in vivo in that specific antisera to omega-1 prevent hepatocyte damage. METHODOLOGY/PRINCIPAL FINDINGS: Using an in vitro culture system employing mouse primary hepatocytes and alanine transaminase (ALT) activity as a marker of heptocyte injury, we demonstrated that S. mansoni eggs, egg-secreted proteins (ESP), soluble-egg antigen (SEA), and omega-1 are directly hepatotoxic and in a dose-dependent manner. Depletion of omega-1 using a monoclonal antibody abolished the toxicity of pure omega-1 and diminished the toxicity in ESP and SEA by 47 and 33%, respectively. Anion exchange chromatography of ESP yielded one predominant hepatotoxic fraction. Proteomics of that fraction identified the presence of IPSE/alpha-1 (IL-4 inducing principle from S. mansoni eggs), a known activator of basophils and inducer of Th2-type responses. Pure recombinant IPSE/alpha-1 also displayed a dose-dependent hepatotoxicity in vitro. Monoclonal antibody depletion of IPSE/alpha-1 abolished the latter's toxicity and diminished the total toxicity of ESP and SEA by 32 and 35%, respectively. Combined depletion of omega-1 and IPSE/alpha-1 diminished hepatotoxicity of ESP and SEA by 60 and 58% respectively. CONCLUSIONS: We identified IPSE/alpha-1 as a novel hepatotoxin and conclude that both IPSE/alpha-1 and omega-1 account for the majority of the hepatotoxicity secreted by S. mansoni eggs. PMID- 22039562 TI - Proteomic analysis of excretory-secretory products of Heligmosomoides polygyrus assessed with next-generation sequencing transcriptomic information. AB - The murine parasite Heligmosomoides polygyrus is a convenient experimental model to study immune responses and pathology associated with gastrointestinal nematode infections. The excretory-secretory products (ESP) produced by this parasite have potent immunomodulatory activity, but the protein(s) responsible has not been defined. Identification of the protein composition of ESP derived from H. polygyrus and other relevant nematode species has been hampered by the lack of genomic sequence information required for proteomic analysis based on database searches. To overcome this, a transcriptome next generation sequencing (RNA-seq) de novo assembly containing 33,641 transcripts was generated, annotated, and used to interrogate mass spectrometry (MS) data derived from 1D-SDS PAGE and LC-MS/MS analysis of ESP. Using the database generated from the 6 open reading frames deduced from the RNA-seq assembly and conventional identification programs, 209 proteins were identified in ESP including homologues of vitellogenins, retinol- and fatty acid-binding proteins, globins, and the allergen V5/Tpx-1-related family of proteins. Several potential immunomodulators, such as macrophage migration inhibitory factor, cysteine protease inhibitors, galectins, C-type lectins, peroxiredoxin, and glutathione S-transferase, were also identified. Comparative analysis of protein annotations based on the RNA-seq assembly and proteomics revealed processes and proteins that may contribute to the functional specialization of ESP, including proteins involved in signalling pathways and in nutrient transport and/or uptake. Together, these findings provide important information that will help to illuminate molecular, biochemical, and in particular immunomodulatory aspects of host-H. polygyrus biology. In addition, the methods and analyses presented here are applicable to study biochemical and molecular aspects of the host-parasite relationship in species for which sequence information is not available. PMID- 22039563 TI - Toward sustainable and comprehensive control of schistosomiasis in China: lessons from Sichuan. AB - Triggered by a fascinating publication in the New England Journal of Medicine detailing China's new multi-pronged strategy to control and eventually interrupt the transmission of Schistosoma japonicum, this PLoS Neglected Tropical Diseases Debate critically examines the generalizability and financial costs of the studies presented from the marshlands of the lake region. Edmund Seto from the University of California and colleagues emphasize that the epidemiology and control of schistosomiasis varies according to the social-ecological context. They conjecture that the successful intervention packages piloted in the lake region is not fully fit for the hilly and mountainous environments in Sichuan and Yunnan provinces, and hence call for more flexible, setting-specific, and less expensive control strategies. In response, Xiao-Nong Zhou from the National Institute of Parasitic Diseases at the Chinese Center of Disease Control and Prevention and colleagues explain the steps from designing pilot studies to the articulation and implementation of a new national control strategy through a careful process of scaling-up and adaptations. Finally, the two opponents converge. The need for integrated, intersectoral, and setting-specific control measures is stressed, supported by rigorous surveillance and continuous research. Experiences and lessons from China are important for shaping the schistosomiasis elimination agenda. PMID- 22039564 TI - Development of face processing. AB - This article reviews the development of the face-processing system from birth, during infancy and through childhood, until it becomes the sophisticated system observed in adults. We begin by discussing the following major theoretical issues concerning the development of face expertise: (1) nature versus nurture or the role of experience in face processing, (2) level of processing (i.e., global, basic, subordinate, individual) and expertise, and (3) type of processing (i.e., holistic, configural, featural). This general overview will be followed by a closer examination of individual studies that investigate the development of face processing. These studies will include a review of (1) development of differential processing of faces and objects, (2) development of differential processing of faces of different species, (3) developmental changes in processing facial identity, and (4) developmental changes in the categorization of faces. Our review of the developmental literature reveals early competence in face processing abilities with infants presenting a preference for face stimuli and facial discrimination using featural, configural, and holistic cues. This early competence is then later refined as evidenced by age-related changes throughout childhood. Some of the refinements are likely due to the development of general cognitive abilities, whereas some others may be face-specific. WIREs Cogni Sci 2011 2 666-675 DOI: 10.1002/wcs.146 This article is categorized under: Psychology > Development and Aging. PMID- 22039565 TI - Emotion and perception: the role of affective information. AB - Visual perception and emotion are traditionally considered separate domains of study. In this article, however, we review research showing them to be less separable than usually assumed. In fact, emotions routinely affect how and what we see. Fear, for example, can affect low-level visual processes, sad moods can alter susceptibility to visual illusions, and goal-directed desires can change the apparent size of goal-relevant objects. In addition, the layout of the physical environment, including the apparent steepness of a hill and the distance to the ground from a balcony can both be affected by emotional states. We propose that emotions provide embodied information about the costs and benefits of anticipated action, information that can be used automatically and immediately, circumventing the need for cogitating on the possible consequences of potential actions. Emotions thus provide a strong motivating influence on how the environment is perceived. WIREs Cogni Sci 2011 2 676-685 DOI: 10.1002/wcs.147 This article is categorized under: Psychology > Emotion and Motivation. PMID- 22039566 TI - Mechanical Loading of Articular Cartilage Reduces IL-1-Induced Enzyme Expression. AB - OBJECTIVE: Exposure of articular cartilage to interleukin-1 (IL-1) results in increased synthesis of matrix degrading enzymes. Previously mechanical load applied together with IL-1 stimulation was found to reduce aggrecan cleavage by ADAMTS-4 and 5 and MMP-1, -3, -9, and -13 and reduce proteoglycan loss from the extracellular matrix. To further delineate the inhibition mechanism the gene expression of ADAMTS-4 and 5; MMP-1, -3, -9, and -13; and TIMP-1, -2, and -3 were measured. DESIGN: Mature bovine articular cartilage was stimulated with a 0.5 MPa compressive stress and 10 ng/ml of IL-1alpha for 3 days and then allowed to recover without stimulation for 1 additional day. The media was assayed for proteoglycan content on a daily basis, while chondrocyte gene expression (mRNA) was measured during stimulation and 1 day of recovery. RESULTS: Mechanical load alone did not change the gene expression for ADAMTS, MMP, or TIMP. IL-1 caused an increase in gene expression for all enzymes after 1 day of stimulation while not affecting the TIMP levels. Load applied together with IL-1 decreased the expression levels of ADAMTS-4 and -5 and MMP-1 and -3 and increased TIMP-3 expression. CONCLUSIONS: A mechanical load appears to modify cartilage degradation by IL-1 at the cellular level by reducing mRNA. PMID- 22039567 TI - The first common cold sore susceptibility gene. PMID- 22039568 TI - C21orf91 genotypes correlate with herpes simplex labialis (cold sore) frequency: description of a cold sore susceptibility gene. AB - BACKGROUND: Herpes simplex virus type 1 (HSV-1) infects >70% of the United States population. We identified a 3-megabase region on human chromosome 21 containing 6 candidate genes associated with herpes simplex labialis (HSL, "cold sores"). METHODS: We conducted single nucleotide polymorphism (SNP) scans of the chromosome 21 region to define which of 6 possible candidate genes were associated with cold sore frequency. We obtained the annual HSL frequency for 355 HSV-1 seropositive individuals and determined the individual genotypes by SNPlex for linkage analysis and parental transmission disequilibrium testing (ParenTDT). RESULTS: Two-point linkage analysis showed positive linkage between cold sore frequency and 2 SNPs within the C21orf91 region, 1 of which is nonsynonymous. ParenTDT analysis revealed a strong association between another C21orf91 SNP, predicted to lie in the 3' untranslated region, and frequent HSL (P = .0047). C21orf 91 is a predicted open reading frame of unknown function that encodes a cytosolic protein. CONCLUSIONS: We evaluated candidate genes in the cold sore susceptibility region using fine mapping with 45 SNP markers. 2 complementary techniques identified C21orf91 as a gene of interest for susceptibility to HSL. We propose that C21orf91 be designated the Cold Sore Susceptibility Gene-1 (CSSG1). PMID- 22039574 TI - Anthrax lethal toxin-induced gene expression changes in mouse lung. AB - A major virulence factor of Bacillus anthracis is the anthrax Lethal Toxin (LeTx), a bipartite toxin composed of Protective Antigen and Lethal Factor. Systemic administration of LeTx to laboratory animals leads to death associated with vascular leakage and pulmonary edema. In this study, we investigated whether systemic exposure of mice to LeTx would induce gene expression changes associated with vascular/capillary leakage in lung tissue. We observed enhanced susceptibility of A/J mice to death by systemic LeTx administration compared to the C57BL/6 strain. LeTx-induced groups of both up- and down-regulated genes were observed in mouse lungs 6 h after systemic administration of wild type toxin compared to lungs of mice exposed to an inactive mutant form of the toxin. Lungs of the less susceptible C57BL/6 strain showed 80% fewer differentially expressed genes compared to lungs of the more sensitive A/J strain. Expression of genes known to regulate vascular permeability was modulated by LeTx in the lungs of the more susceptible A/J strain. Unexpectedly, the largest set of genes with altered expression was immune specific, characterized by the up-regulation of lymphoid genes and the down-regulation of myeloid genes. Transcripts encoding neutrophil chemoattractants, modulators of tumor regulation and angiogenesis were also differentially expressed in both mouse strains. These studies provide new directions for the investigation of vascular leakage and pulmonary edema induced by anthrax LeTx. PMID- 22039575 TI - THE INDO-PACIFIC GEMMULA SPECIES IN THE SUBFAMILY TURRINAE: ASPECTS OF FIELD DISTRIBUTION, MOLECULAR PHYLOGENY, RADULAR ANATOMY AND FEEDING ECOLOGY. AB - The biology, feeding ecology and phylogenetic relationships of marine snails in the family Turridae remain poorly understood. Here we report our study on four deep-water species in the genus Gemmula, a major group in this family. The four species G. speciosa (Reeve 1843), G. sogodensis (Olivera 2005), G. kieneri (Doumet 1940) and G. diomedea (Powell 1964) were collected at five different sites in the Philippines, and their pattern of distribution in the sites, their feeding behaviour as well as their phylogenetic relationships with each other and with other members of the subfamily Turrinae were investigated. The radular morphology (of two Gemmula species) and potential prey (for one Gemmula species) were also examined. Actual feeding observations were also conducted for Gemmula speciosa and compared with two turrids from other genera.All four Gemmula species showed strikingly different patterns of distribution; each species was found to be relatively much more abundant at one site but not at the other sites. Molecular phylogenetic analysis based on 16S sequences correlated with previously reported 12S sequences and revealed that the four species all belong to a well supported Gemmula clade within the subfamily Turrinae; and that this clade appeared more closely related to the clades Xenuroturris, Turris and Lophiotoma than to the other clades in the subfamily (i.e., Turridrupa, Unedogemmula and Polystira). Morphological analysis of the radula of both G. speciosa and G. sogodensis revealed that the radulae of the two species were similar but differed from the other turrids, Lophiotoma acuta and Unedogemmula bisaya, by the absence of central teeth, consistent with the separation of the Gemmula clade from the Lophiotoma and Unedogemmula clade.To identify the polychaete group that is targeted as prey by species of Gemmula, analysis of regurgitated food fragments was made; phylogenetic analysis of an mtCOI gene fragment that was PCR-amplified from the regurgitated tissue of one specimen (G. diomedea) indicated close affinity of the prey to the terebellid polychaete Amphitritides. Specimens of Gemmula speciosa, when challenged with the terebellid polychaete Loimia sp., were observed to attack the worm suggesting that Gemmula species feed on terebellid polychaetes. Lophiotoma acuta were also observed to feed on the same species of terebellid but were usually group-feeding in contrast to the solitary feeding of G. speciosa. Unedogemmula bisaya did not feed on the terebellid which also supports the separation of the Gemmula and Unedogemmula clade.Two lines of proof (i.e. the molecular phylogenetic analysis and the feeding challenge) supporting the toxin homology findings previously reported, provide consistent evidence that Gemmula is a distinct clade of worm-hunting Turrinae that feeds on Terebellidae. PMID- 22039577 TI - Evaluation of F-nifene binding to alpha4beta2 nicotinic receptors in the rat brain using microPET imaging. AB - MicroPET imaging studies using (18)F-nifene, a new positron emission tomography (PET) radiotracer for nicotinic acetylcholinergic receptors (nAChR) alpha4beta2 receptors in rats, have been carried out. Rats were imaged for 90 min after intravenous injection of (18)F-nifene (0.8 to 1 mCi), and binding potential (BP(ND)) was measured. (18)F-Nifene binding to thalamic and extrathalamic brain regions was consistent with the alpha4beta2 nAChR distribution in the rat brain. Using the cerebellum as a reference, the values for the thalamus varied less than 5% (BP(ND) = 1.30, n = 3), confirming reproducibility of (18)F-nifene binding. (18)F-Nifene microPET imaging was also used to evaluate effects of nicotine in a group of Sprague-Dawley rats under isoflurane anesthesia. Nicotine challenge postadministration of (18)F-nifene demonstrated reversibility of (18)F-nifene binding in vivo. For alpha4beta2 nAChR receptor occupancy (nAChR(OCC)), various doses of nicotine (0, 0.02, 0.1, 0.25, and 0.50 mg/kg nicotine free base) 15 min prior to (18)F-nifene were administered. Low-dose nicotine (0.02 mg) reached > 80% nAChR(OCC) while at higher doses (0.25 mg) > 90% nAChR(OCC) was measured. The small amount of (18)F-nifene binding with reference to the cerebellum affects an accurate evaluation of nAChR(OCC). Efforts are underway to identify alternate reference regions for (18)F-nifene microPET studies in rodents. PMID- 22039576 TI - Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. AB - Immune-regulated pathways influence multiple aspects of cancer development. In this article we demonstrate that both macrophage abundance and T-cell abundance in breast cancer represent prognostic indicators for recurrence-free and overall survival. We provide evidence that response to chemotherapy is in part regulated by these leukocytes; cytotoxic therapies induce mammary epithelial cells to produce monocyte/macrophage recruitment factors, including colony stimulating factor 1 (CSF1) and interleukin-34, which together enhance CSF1 receptor (CSF1R) dependent macrophage infiltration. Blockade of macrophage recruitment with CSF1R signaling antagonists, in combination with paclitaxel, improved survival of mammary tumor-bearing mice by slowing primary tumor development and reducing pulmonary metastasis. These improved aspects of mammary carcinogenesis were accompanied by decreased vessel density and appearance of antitumor immune programs fostering tumor suppression in a CD8+ T-cell-dependent manner. These data provide a rationale for targeting macrophage recruitment/response pathways, notably CSF1R, in combination with cytotoxic therapy, and identification of a breast cancer population likely to benefit from this novel therapeutic approach. SIGNIFICANCE: These findings reveal that response to chemotherapy is in part regulated by the tumor immune microenvironment and that common cytotoxic drugs induce neoplastic cells to produce monocyte/macrophage recruitment factors, which in turn enhance macrophage infiltration into mammary adenocarcinomas. Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8+ T-cell-dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy. PMID- 22039578 TI - Limited liver resection: a good indication for the treatment of hepatocellular carcinoma in elderly patients. AB - OBJECTIVE: Hepatocellular carcinoma is often diagnosed in elderly people. METHODS: One hundred and seventy-five patients older than 70 years were operated on for hepatocellular carcinoma (Group 1). The results were compared with 276 resected patients younger than 70 (Group 2) and to 108 aged patients with chronic liver disease without hepatocellular carcinoma (Group 3). RESULTS: Hepatocellular carcinoma in the elderly is more frequently associated with hepatitis C virus, less frequently capsulated and less frequently diagnosed by screening programs than in young patients. After resection, no difference was noted in post operative complications and in mortality rates (3.2%); major hepatic resection in cirrhosis carried a high risk of death (22%). Five years survival was 42%, comparable with the young surgical patients but significantly lower than the medical patients in Group 3. Recurrence of hepatocellular carcinoma was the main reason of death, but it was suitable for a radical treatment in 37.6% of cases, including surgery, with a mean survival of 31 months. CONCLUSIONS: Liver resection is a valid option for the treatment of hepatocellular carcinoma in the elderly; major resections in cirrhotic old patients must be reserved for selected cases. Recurrence may be suitable of a radical approach, including surgery. PMID- 22039579 TI - Tumor and breast volume ratio as a predictive factor for axillary lymph node metastases in T1c ductal invasive breast cancer: prospective observational clinico-pathological study. AB - OBJECTIVE: The status of the axilla is the single most important prognostic indicator of overall survival in patients with breast cancer. Sentinel-node biopsy has false-negative rates of 5-10%. The aim of this study was to assess the importance of tumor and breast volume ratio as a predictive factor for axillary lymph node metastases in patients with T1c ductal invasive breast cancer. METHODS: This study included 136 consecutive patients with T1c ductal invasive breast cancer. Three tumor diameters were measured. Tumor volume was calculated by the formula for ellipse. Breast volume was measured preoperatively. Tumor and breast volume ratio was calculated and shown per thousand. RESULTS: Tumor and breast volume ratio is a new independent predictive factor for axillary lymph node metastase in T1c ductal invasive breast cancer. CONCLUSIONS: This predictive factor could help to define a subgroup of patients who will be at a higher risk for axillary lymph node metastase and would benefit from additional close follow up or axillary lymph node dissection. PMID- 22039580 TI - Pyridine encapsulated hyperbranched polymers as mimetic models of haeme containing proteins, that also provide interesting and unusual porphyrin-ligand geometries. AB - This communication describes the use of non-covalent chemistry to construct recyclable porphyrin cored HBPs. The non-covalent design allows the polymeric backbone to be rescued and reused after porphyrin degradation. The steric environment within the polymeric encapsulated ligand notably affected the porphyrin coordination geometry. PMID- 22039581 TI - Severe hepatocellular disease in mice lacking one or both CaaX prenyltransferases. AB - Protein farnesyltransferase (FTase) and protein geranylgeranyltransferase-I (GGTase-I) add 15- or 20-carbon lipids, respectively, to proteins that terminate with a CaaX motif. These posttranslational modifications of proteins with lipids promote protein interactions with membrane surfaces in cells, but the in vivo importance of the CaaX prenyltransferases and the protein lipidation reactions they catalyze remain incompletely defined. One study concluded that a deficiency of FTase was inconsequential in adult mice and led to little or no tissue pathology. To assess the physiologic importance of the CaaX prenyltransferases, we used conditional knockout alleles and an albumin-Cre transgene to produce mice lacking FTase, GGTase-I, or both enzymes in hepatocytes. The hepatocyte-specific FTase knockout mice survived but exhibited hepatocellular disease and elevated transaminases. Mice lacking GGTase-I not only had elevated transaminases but also had dilated bile cannaliculi, hyperbilirubinemia, hepatosplenomegaly, and reduced survival. Of note, GGTase-I-deficient hepatocytes had a rounded shape and markedly reduced numbers of actin stress fibers. Hepatocyte-specific FTase/GGTase I double-knockout mice closely resembled mice lacking GGTase-I alone, but the disease was slightly more severe. Our studies refute the notion that FTase is dispensable and demonstrate that GGTase-I is crucial for the vitality of hepatocytes. PMID- 22039583 TI - NHC-carbene cyclopentadienyl iron based catalyst for a general and efficient hydrosilylation of imines. AB - A general and efficient hydrosilylation of imines catalysed by a well defined NHC carbene cyclopentadienyl iron complex has been developed. Both aldimines and ketimines are converted to the corresponding amines under mild conditions, and under visible light activation. PMID- 22039582 TI - Endothelial expression of human ABCA1 in mice increases plasma HDL cholesterol and reduces diet-induced atherosclerosis. AB - The role of endothelial ABCA1 expression in reverse cholesterol transport (RCT) was examined in transgenic mice, using the endothelial-specific Tie2 promoter. Human ABCA1 (hABCA1) was significantly expressed in endothelial cells (EC) of most tissues except the liver. Increased expression of ABCA1 was not observed in resident peritoneal macrophages. ApoA-I-mediated cholesterol efflux from aortic EC was 2.6-fold higher (P < 0.0001) for cells from transgenic versus control mice. On normal chow diet, Tie2 hABCA1 transgenic mice had a 25% (P < 0.0001) increase in HDL-cholesterol (HDL-C) and more than a 2-fold increase of eNOS mRNA in the aorta (P < 0.04). After 6 months on a high-fat, high-cholesterol (HFHC) diet, transgenic mice compared with controls had a 40% increase in plasma HDL-C (P < 0.003) and close to 40% decrease in aortic lesions (P < 0.02). Aortas from HFHC-fed transgenic mice also showed gene expression changes consistent with decreased inflammation and apoptosis. Beneficial effects of the ABCA1 transgene on HDL-C levels or on atherosclerosis were absent when the transgene was transferred onto ApoE or Abca1 knockout mice. In summary, expression of hABCA1 in EC appears to play a role in decreasing diet-induced atherosclerosis in mice and is associated with increased plasma HDL-C levels and beneficial gene expression changes in EC. PMID- 22039584 TI - Substituent and counterion effects on the formation of pi-dimer dications of end capped heptathienoacenes. AB - We have investigated the impact of the functionalization and the chemical nature of counterions on the pi-dimer dications formation in two end-capped heptathienoacenes. Radical cations of an alpha-substituted heptathienoacene with triisopropylsilyl groups do not pi-dimerize, while those of an alpha,beta substituted heptathienoacene with four n-decyl side chains show a high propensity toward pi-dimerization, increased by PF(6)(-) counterions. PMID- 22039585 TI - Pathogenic aberrations revealed exclusively by single nucleotide polymorphism (SNP) genotyping data in 5000 samples tested by molecular karyotyping. AB - BACKGROUND: Several recent studies have demonstrated the use of single nucleotide polymorphism (SNP) arrays for the investigation of intellectual disability, developmental delay, autism or congenital abnormalities. In addition to LogR 'copy number' data, these arrays provide SNP genotyping data for gene level autozygosity mapping, estimating low levels of mosaicism, assessing long continuous stretches of homozygosity (LCSH), detection of uniparental disomy, and 'autozygous' regions. However, there remains little specific information on the clinical utility of this genotyping data. METHODS: Molecular karyotyping, using SNP array, was performed on 5000 clinical samples. RESULTS: Clinically significant 'LogR neutral' genotyping abnormalities were detected in 0.5% of cases. Among these were a single case of chimerism, 12 cases with low level chromosome mosaicism, and 11 cases with an LCSH associated with uniparental disomy. In addition, the genotyping data revealed several LCSH associated with clinically relevant 'recessive type' genetic defects. CONCLUSIONS: These results demonstrate the utility of SNP genotyping data for detection of clinically significant abnormalities, including chimerism/mosaicism and recessive Mendelian disorders associated with autozygosity. The incidence of clinically significant low level mosaicism inferred from these cases suggests that this has hitherto been underestimated and chromosome mosaicism frequently occurs in the absence of indicative clinical features. The growing appreciation among clinicians and demand for SNP genotyping data poses significant challenges for the interpretation of LCSH, especially where there is no detailed phenotypic description to direct laboratory analysis. Finally, reporting of unexpected or hidden consanguinity revealed by SNP array analysis raises potential ethical and legal issues. PMID- 22039586 TI - Polyacrylamide hydrogels as substrates for studying bacteria. AB - Polyacrylamide hydrogels can be used as chemically and physically defined substrates for bacterial cell culture, and enable studies of the influence of surfaces on cell growth and behaviour. PMID- 22039587 TI - Hydrogen bonds in protic ionic liquids and their correlation with physicochemical properties. AB - The temperature dependence of the N-H proton chemical shift in protic ionic liquids (PILs) and FT-IR spectra of the N-H bonds indicated the presence of strong hydrogen bonds between the protonated cation and the anion, depending on the DeltapK(a) of the constituent acid and base, and their successive breaking with temperature, which may explain the characteristic properties of PILs such as relatively low ionicity and its decrease with temperature. PMID- 22039588 TI - Graphene oxide: an efficient and reusable carbocatalyst for aza-Michael addition of amines to activated alkenes. AB - Graphene oxide was found to be a highly efficient, reusable and cost-effective organocatalyst for the aza-Michael addition of amines to activated alkenes to furnish corresponding beta-amino compounds in excellent yields. PMID- 22039589 TI - Exploiting nature's rich source of proteasome inhibitors as starting points in drug development. AB - Cancer is the No. 2 cause of death in the Western world and one of the most expensive diseases to treat. Thus, it is not surprising, that every major pharmaceutical and biotechnology company has a blockbuster oncology product. In 2003, Millennium Pharmaceuticals entered the race with Velcade(r), a first-in class proteasome inhibitor that has been approved by the FDA for treatment of multiple myeloma and its sales have passed the billion dollar mark. Velcade(r)'s extremely toxic boronic acid pharmacophore, however, contributes to a number of severe side effects. Nevertheless, the launching of this product has validated the proteasome as a target in fighting cancer and further proteasome inhibitors have entered the market as anti-cancer drugs. Additionally, proteasome inhibitors have found application as crop protection agents, anti-parasitics, immunosuppressives, as well as in new therapies for muscular dystrophies and inflammation. Many of these compounds are based on microbial metabolites. In this review, we emphasize the important role of the structural elucidation of the various unique binding mechanisms of these compounds that have been optimized throughout evolution to target the proteasome. Based on this knowledge, medicinal chemists have further optimized these natural products, resulting in potential drugs with reduced off-target activities. PMID- 22039590 TI - Guest editor's introduction special section on the Virtual Reality Conference (VR). PMID- 22039591 TI - Letter from the editor: the fragility of medicine. PMID- 22039592 TI - Letter from the Chairman & CEO: national health reform takes center stage. PMID- 22039593 TI - European Medicines Agency review of post-authorisation studies with implications for the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. AB - PURPOSE: A review of post-authorisation studies requested in 2007 by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) was undertaken to determine compliance and the need for research capacity in the European Union (EU), with implications for the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). METHODS: Information from the EMA's electronic records management systems was analysed. RESULTS: As of 31 January 2010, of the 60 relevant studies identified, 52 had been progressed to being able to start data collection (including six merged into a single study). Of the remaining eight studies, the agreement of the CHMP that a proposed study was no longer required is documented for six, with a final decision having not been reached for another study and an acknowledgement by the CHMP that a further study would not be progressed. Of the 47 studies that could therefore have commenced data collection or extraction, 38 were ongoing, four were complete and five had not yet started. Most studies were conducted within the EU. CONCLUSION: Compliance with the request of the CHMP to conduct studies is very good. The review identified the need for careful consideration of the necessity of studies and of timely dialogue on protocols in advance of a CHMP opinion. The need for expertise and capacity within the EU for the conduct of post-authorisation studies is confirmed. ENCePP as a transparency and excellence network and as an initiative to build research capacity will enhance post authorisation medicines research. PMID- 22039594 TI - Major bleeding risk associated with warfarin and co-medications in the elderly population. AB - PURPOSE: Warfarin management in the elderly population is complex as medicines prescribed for concomitant diseases may further increase the risk of major bleeding associated with warfarin use. We aimed to quantify the excess risk of bleeding-related hospitalisation when warfarin was co-dispensed with potentially interacting medicines. METHODS: A retrospective cohort study was undertaken over a 4-year period from July 2002 to June 2006 to examine bleeding risk associated with medications co-administered in patients taking warfarin using an administrative claims database from the Australian Department of Veterans' Affairs. All veterans aged 65 years and over who were new users of warfarin were followed until death or study end. Risk of bleeding was assessed using a Poisson GEE model adjusting for age, gender, socioeconomic status, co-morbidity index, previous bleeding related hospitalisations and indicators of health service use. RESULTS: Overall, 17661 veterans who used warfarin at any time during the study period were included. The overall incidence rate of bleeding-related hospitalisations was 4.1 (95% CI 3.7-4.6) per 100 person-years in veterans who were not receiving potentially interacting medicines. Bleeding-related hospitalisation rates were significantly increased when warfarin was co prescribed with low-dose aspirin (Adjusted rate ratio (AdjRR) 1.44, 95% CI 1.00 2.07), clopidogrel (AdjRR 2.23, 95% CI 1.48-3.36), clopidogrel with aspirin (AdjRR 3.44, 95% CI 1.28-9.23), amiodarone (AdjRR 3.33, 95% CI 1.38-8.00) and antibiotics (AdjRR 2.34, 95% CI 1.55-3.54). CONCLUSIONS: Models assessing bleeding risk with warfarin should take account of the range of potentially harmful medicine combinations used in elderly people with comorbid conditions. PMID- 22039595 TI - A novel superhydrophilic and underwater superoleophobic hydrogel-coated mesh for oil/water separation. PMID- 22039596 TI - Clicking well-defined biodegradable nanoparticles and nanocapsules by UV-induced thiol-ene cross-linking in transparent miniemulsions. PMID- 22039598 TI - Integrated carbon nanotube array as dry adhesive for high-temperature silicon processing. PMID- 22039597 TI - Mineral coatings for temporally controlled delivery of multiple proteins. PMID- 22039599 TI - Surface-initiated phase separation--fabrication of two-layer organic light emitting devices in a single processing step. PMID- 22039600 TI - Minority carrier lifetime and surface effects in VLS-grown axial p-n junction silicon nanowires. PMID- 22039601 TI - Bending materials with light: photoreversible macroscopic deformations in a disordered polymer. PMID- 22039602 TI - Interfacial mechanics of carbon nanotube@amorphous-Si coaxial nanostructures. PMID- 22039603 TI - Self-assembled transparent conductive electrodes from Au nanoparticles in surfactant monolayer templates. PMID- 22039604 TI - Analysis of visual toxicity after gamma knife radiosurgery for treatment of choroidal melanoma: identification of multiple targets and mechanisms of toxicity. AB - OBJECTIVES: Identification of the targets of radiation damage after radiosurgical treatment of ocular melanoma will potentially allow for sparing of vision with improved treatment planning. MATERIALS AND METHODS: Six patients with ocular melanoma, who had useful vision before therapy, were treated with gamma knife stereotactic radiosurgery with curative intent. Dosimetric analysis of functional targets of radiation damage including the fovea, optic nerve, lens, and iris was carried out. Serial testing of visual acuity and fundoscopic examination were carried out after treatment. RESULTS: Visual sparing was achieved in 3 of 6 patients at last followup with a median follow-up of 2 years. The causes of loss of vision in those patients who lost useful vision were retinal detachment, neovascular glaucoma, and optic neuropathy. CONCLUSIONS: Preradiosurgical size and location are likely predictors of posttreatment visual outcomes. PMID- 22039605 TI - Inducible cassette exchange: a rapid and efficient system enabling conditional gene expression in embryonic stem and primary cells. AB - Genetic modification is critically enabling for studies addressing specification and maintenance of cell fate; however, methods for engineering modifications are inefficient. We demonstrate a rapid and efficient recombination system in which an inducible, floxed cre allele replaces itself with an incoming transgene. We target this inducible cassette exchange (ICE) allele to the (HPRT) locus and demonstrate recombination in murine embryonic stem cells (ESCs) and primary cells from derivative ICE mice. Using lentivectors, we demonstrate recombination at a randomly integrated ICE locus in human ESCs. To illustrate the utility of this system, we insert the myogenic regulator, Myf5, into the ICE locus in each platform. This enables efficient directed differentiation of mouse and human ESCs into skeletal muscle and conditional myogenic transdetermination of primary cells cultured in vitro. This versatile tool is thus well suited to gain-of-function studies probing gene function in the specification and reprogramming of cell fate. PMID- 22039606 TI - Readmission rates after abdominal surgery: the role of surgeon, primary caregiver, home health, and subacute rehab. AB - OBJECTIVE: To prospectively evaluate predictive factors of hospital readmission rates in patients undergoing abdominal surgical procedures. BACKGROUND: Recommendations from MedPAC that the Centers for Medicare and Medicaid Services (CMS) report upon and determine payments based in part on readmission rates have led to an attendant interest by payers, hospital administrators and far-sighted physicians. METHODS: Analysis of 266 prospective treated patients undergoing major abdominal surgical procedures from September 2009 to September 2010. All patients were prospectively evaluated for underlying comorbidities, number of preop meds, surgical procedure, incision type, complications, presence or absence of primary and/or secondary caregiver, their education level, discharge number of medications, and discharge location. Univariate and multivariate analyses were performed. RESULTS: Two hundred twenty-six patients were reviewed with 48 (18%) gastric-esophageal, 39(14%) gastrointestinal, 88 (34%) liver, 58 (22%) pancreas, and 33 (12%) other. Seventy-eight (30%) were readmitted for various diagnoses the most common being dehydration (26%). Certain preoperative and intraoperative factors were not found to be significant for readmission being, comorbidities, diagnosis, number of preoperative medications, patient education level, type of operation, blood loss, and complications. Significant predictive factors for readmission were age (>=69 years), number of discharged (DC) meds (>=9 medications), <=50% oral intake (52% vs. 23%), and DC home with a home health agency (62% vs. 11%) CONCLUSION: Readmission rates for surgeons WILL become a quality indicator of performance. Quality parameters among Home Health agencies are nonexistent, but will reflect on surgeon's performance. Greater awareness regarding predictors of readmission rates is necessary to demonstrate improved surgical quality. PMID- 22039607 TI - Toroidal micelles of polystyrene- block -poly(acrylic acid). PMID- 22039608 TI - Cost-effectiveness of the National Surgical Quality Improvement Program. AB - OBJECTIVE: The purpose of this study was to compare the cost-effectiveness of the National Surgical Quality Improvement Program (NSQIP) at an academic medical center between the first 6 months and through the first and second years of implementation. BACKGROUND: The NSQIP has been extended to private-sector hospitals since 1999, but little is known about its cost-effectiveness. METHODS: Data included 2229 general or vascular surgeries, 699 of which were conducted after NSQIP was in place for 6 months. We estimated an incremental cost effectiveness ratio (ICER) comparing costs and benefits before and after the adoption of NSQIP. Costs were estimated from the perspective of the hospital and included hospital costs for each admission plus the total annual cost of program adoption and maintenance, including administrator salary, training, and information technology costs. Effectiveness was defined as events avoided. Confidence intervals and a cost-effectiveness acceptability curve were computed by using a set of 10,000 bootstrap replicates. The time periods we compared were (1) July 2007 to December 2007 to July 2008 to December 2008 and (2) July 2007 to June 2008 to July 2008 to June 2009. RESULTS: The incremental costs of the NSQIP program were $832 and $266 for time periods 1 and 2, respectively, yielding ICERs of $25,471 and $7319 per event avoided. The cost-effectiveness acceptability curves suggested a high probability that NSQIP was cost-effective at reasonable levels of willingness to pay. CONCLUSIONS: In these data, not only did NSQIP appear cost-effective, but also its cost-effectiveness improved with greater duration of participation in the program, resulting in a decline to 28.7% of the initial cost. PMID- 22039609 TI - Brief report: chimeric pigs produced from induced pluripotent stem cells demonstrate germline transmission and no evidence of tumor formation in young pigs. AB - The recent development of porcine induced pluripotent stem cells (piPSCs) capable of generating chimeric animals, a feat not previously accomplished with embryonic stem cells or iPSCs in a species outside of rodents, has opened the doors for in depth study of iPSC tumorigenicity, autologous transplantation, and other key aspects to safely move iPSC therapies to the clinic. The study of iPSC tumorigenicity is critical as previous research in the mouse showed that iPSC derived chimeras possessed large numbers of tumors, rising significant concerns about the safety of iPSC therapies. Additionally, piPSCs capable of generating germline chimeras could revolutionize the transgenic animal field by enabling complex genetic manipulations (e.g., knockout or knockin of genes) to produce biomedically important large animal models or improve livestock production. In this study, we demonstrate for the first time in a nonrodent species germline transmission of iPSCs with the live birth of a transgenic piglet that possessed genome integration of the human POU5F1 and NANOG genes. In addition, gross and histological examination of necropsied porcine chimeras at 2, 7, and 9 months showed that these animals lacked tumor formation and demonstrated normal development. Tissue samples positive for human POU5F1 DNA showed no C-MYC gene expression, further implicating C-MYC as a cause of tumorigenicity. The development of germline-competent porcine iPSCs that do not produce tumors in young chimeric animals presents an attractive and powerful translational model to study the efficacy and safety of stem cell therapies and perhaps to efficiently produce complex transgenic animals. PMID- 22039610 TI - Use of a chondroitin sulfate isomer as an effective and removable dispersant of single-walled carbon nanotubes. AB - Three isomers of chondroitin sulfate (CS), i.e., CS-A, CS-B, and CS-C, are investigated as nanotube dispersants and are found to have vastly different abilities to disperse single-walled carbon nanotubes (SWNTs) in water due to their different intramolecular interactions. Only CS-A and CS-C effectively disperse SWNTs into small bundles or individual tubes while CS-B disperses SWNTs poorly. Computer simulation and circular dichrosim show that neat CS-A and CS-C have weak intramolecular hydrogen bonding and extended conformations in solution resulting in energetically more favorable interactions with nanotubes. CS-B has relatively strong intramolecular Coulombic interaction and more alpha-helical secondary structure in solution resulting in energetically less favorable interaction with the nanotubes. Atomic force microscopy images show helical wrappings of CS-A and CS-C around the SWNTs. Transmission electron microscopy corroborates the helical wrapping of CS-A. Different isomeric forms of a polymer can have vastly different dispersing power because of their different intramolecular interactions and conformations. The easy removability of CS-A from nanotubes is confirmed with X-ray photoelectron spectroscopy showing almost no detectable sulphur content after washing with water and by application of washed CS-A dispersed SWNTs in field-effect transistors. PMID- 22039611 TI - Fabrication of silicon/polymer composite nanopost arrays and their sensing applications. AB - A novel technique is reported for fabricating silicon/polymer composite nanopost arrays by combining colloidal lithography and surface-initiated atom-transfer radical polymerization. The composite nanopost arrays possess a core/shell nanoarchitecture, with shells of poly(2-hydroxyethyl methacrylate) and cores of silicon nanoposts. The polymer brush possesses quasi-3D homogeneous nanoarchitectures due to the controllable polymerization process using the surface-initiated atom-transfer radical polymerization technique. The composite nanopost arrays are durable due to the particular nanoarchitectures. The backbone templates of the composites are silicon nanopost arrays directly etched from silicon substrates, and the polymer shell is covalently grafted from the arrays. The composite nanopost arrays exhibit vivid colors. Moreover, the colors of the composite nanopost arrays can be tuned from green to red by changing the thickness of fi lm. Specifically, the composite nanopost arrays can be used as sensors to rapidly detect water vapors with high stability and reproducibility. Many different functional surfaces could be prepared through this technique using other functional monomers. PMID- 22039612 TI - Second brain death examination may negatively affect organ donation. PMID- 22039613 TI - Second brain death examination may negatively affect organ donation. PMID- 22039614 TI - On the nonidentifiability of migration time estimates in isolation with migration models. PMID- 22039615 TI - Study shows Keystone program achieved significant savings. AB - Study helps relieve dearth of evidence that QI programs save money. Savings range from four times the cost of initiative to more than ten times the cost. Human capital represents the single largest component of hospital costs. PMID- 22039616 TI - Teach-back program reduces readmissions. AB - Work group reviews the literature for evidence-based models to emulate. EMR reminder includes a description of program for nurses logging on. Extensive staff education helps set up the initiative for success. PMID- 22039617 TI - CM enhances telemedicine program. AB - Program achieves reduced ED visits, hospitalizations, and mortality, plus 13% in cost savings. Medicare demonstration project involved patients with diabetes, COPD, heart failure, and co-morbidities. Patients are asked questions specifically related to factors that could exacerbate their disease. PMID- 22039618 TI - Nocturnists help avoid night, weekend danger. PMID- 22039620 TI - TJC readies new performance standard. PMID- 22039619 TI - Response changes as gram neg HAIs rise. PMID- 22039621 TI - Preserve vascular health to lower risk of dementia. Treating atherosclerosis may help preserve cognitive function later in life. PMID- 22039622 TI - What are the benefits of eating more fruit? PMID- 22039623 TI - Post-heart attack fracture risk increases. But the odds of surviving that heart attack are better than ever--almost doubled since 1979. PMID- 22039624 TI - Soluble fiber helps reduce visceral fat. An apple a day, along with a cup of beans, could help reduce the dangerous fat that lies deep in the abdomen and surrounds vital organs. PMID- 22039625 TI - Cigarette smoke alters airway tissue in chronic obstructive pulmonary disease. Lung damage appears to last long after exposure to smoke ends, but quitting at any age has beneficial effects. PMID- 22039626 TI - Possible gender link in knee injuries; males at higher risk. Researchers see an association between gender and severity of cartilage lesions. PMID- 22039628 TI - I've heard of a treatment for prostate cancer called "focal therapy" that is said to be organ-sparing and may have fewer side effects than more traditional treatments. What can you tell me about this? PMID- 22039627 TI - I find myself becoming increasing distracted when I try to concentrate, whether it's reading, working on the computer or tackling my correspondence. Are there any self-help suggestions or is this simply a function of aging that I should get used to? PMID- 22039629 TI - 50 years old and looking great. PMID- 22039630 TI - "Drug-besotten, sin-begotten fiends of filth": New Zealanders and the Oriental other, 1850-1920. PMID- 22039631 TI - Temperance, Father Mathew, and the Irish clergy. PMID- 22039632 TI - The dark side of democracy: the modern tradition of ethnic cleansing and political cleansing. PMID- 22039633 TI - The politics of poor relief in the late Ottoman Empire, 1876-1914. PMID- 22039634 TI - [Rice cultivation in Tonkin from the late 19th century to the mid-20th century]. PMID- 22039635 TI - Anti-Darwinism in France: science and the myth of nation. PMID- 22039636 TI - Direct farming on the estates of Cheshire landowners, c. 1570-c. 1700. PMID- 22039637 TI - Epidemics and public health in late colonial Somaliland. PMID- 22039638 TI - Gynocentric matrimony: the fin-de-siecie alliance of Rosa Bonheur and Anna Klumpke. PMID- 22039639 TI - Homoeroticism and the quest for originality in Girodet's "Revolt at Cairo" (1810). PMID- 22039640 TI - Linguistic analysis of the 1994 Ethiopian census. PMID- 22039641 TI - Romanticism and the end of childhood. PMID- 22039642 TI - The company of women. PMID- 22039643 TI - The "Eastern-woman question": Martineau and Nightingale visit the harem. PMID- 22039644 TI - "The Hound of the Baskervilles," the Man on the Tor , and a metaphor for the mind. PMID- 22039645 TI - An interview with Dr Michael MacEntee. PMID- 22039646 TI - [Women's activities and roles in times of significant social change]. PMID- 22039647 TI - "You don't make a torpedo gunner out of a drunkard": Agnes Weston, temperance, and the British navy. PMID- 22039648 TI - Landlord policies and population change in north-east Scotland and the Western Isles, 1755-1841. PMID- 22039649 TI - [Childhood economies: material resources and the management of inheritances for Extremadura orphans during the modern age]. PMID- 22039650 TI - ["Single" women in semiurban Galician society in the 18th century]. PMID- 22039651 TI - Rationalizing charity in fifteenth-century Milan: the "Scuola delle quattro Marie" (1447-1451). PMID- 22039652 TI - The premier body: Sarah Netanyahu, Nava Barak, and the discourse of womanhood in Israel. PMID- 22039653 TI - Wives, widows, and workers: Corazon Aquino, Imelda Marcos, and the Filipina "other". PMID- 22039654 TI - [The investment patterns and lifestyle of the cosmopolitan merchants of Trieste toward the end of the 19th century]. PMID- 22039655 TI - [The abolishment of the rationing system in the USSR in 1934-35]. PMID- 22039656 TI - Can China be a clean tiger?: Growth strategies and environmental realities. PMID- 22039657 TI - [Russia's population at the turn of the 20th century]. PMID- 22039658 TI - Management of organisational changes in a case of de-institutionalisation. AB - PURPOSE: This paper seeks to explore the development of a discharge programme in one learning disability hospital in Scotland. The study aims to concentrate on organisational developmental changes in that institution. The model of the management during the discharge programme was investigated. The aim of the study is to explore how the discharge programme developed, as seen under the lens of organisational change, in order to find out what kind of model of management is more suitable in similar programmes. DESIGN/METHODOLOGY/APPROACH: A case study was employed. Data were collected by means of interviews. The interviews followed a structured format. The sample of the study had to be a purposive sample and the method of snowball sampling was used; finally, 28 interviews were conducted. A grounded approach was adopted for the data analysis. The software program QSR "NUD*IST" (version "N6") was used as a technical tool, in order to facilitate the data analysis. FINDINGS: The findings of this study show that various management models were adopted in the four phases of the discharge programme. These different models represent a "quest" by the institution's management regarding the most appropriate model for managing the discharge programme. This study shows that this goes on continuously in organisations under transition until they settle down to a more permanent state. ORIGINALITY/VALUE: It was concluded that management models, which are composed of characteristics from the organic theory of organisational management, could apply in discharge programmes. The data gathered enabled the researcher to arrive at a model of management which is suitable for managing organisational changes in discharge programmes, the named "stakeholder management model". PMID- 22039659 TI - Power in health care organizations: contemplations from the first-line management perspective. AB - PURPOSE: The aim of this paper is to examine health care organizations' power structures from the first-line management perspective. What liable power structures derive from the theoretical bases of bureaucratic, professional and result based organizations, and what power type do health care organizations represent, according to the empirical data? The paper seeks to perform an analysis using Mintzberg's power configurations of instrument, closed system, meritocracy and political arena. DESIGN/METHODOLOGY/APPROACH: The empirical study was executed at the end of 2005 through a survey in ten Finnish hospital districts in both specialized and primary care. Respondents were all first-line managers in the area and a sample of staff members from internal disease, surgical and psychiatric units, as well as out-patient and primary care units. The number of respondents was 1,197 and the response percentage was 38. The data were analyzed statistically. FINDINGS: As a result, it can be seen that a certain kind of organization structure supports the generation of a certain power type. A bureaucratic organization generates an instrument or closed system organization, a professional organization generates meritocracy and also political arena, and a result-based organization has a connection to political arena and meritocracy. First line managers regarded health care organizations as instruments when staff regarded them mainly as meritocracies having features of political arena. Managers felt their position to be limited by rules, whereas staff members regarded their position as having lots of space and influence potential. PRACTICAL IMPLICATIONS: If the organizations seek innovative and active managers at the unit level, they should change the organizational structure and redistribute the work so that there could be more space for meaningful management. ORIGINALITY/VALUE: This research adds to the literature and gives helpful suggestions that will be of interest to those in the position of first line management in health care. PMID- 22039660 TI - Barriers to implementing health sector administrative decentralisation in Ghana: a study of the Nkwanta district health management team. AB - PURPOSE: This paper aims to examine empirically the ways in which workforce knowledge and organisational factors of an implementing agency affected the implementation of health sector administration decentralisation in Ghana with insights from the Nkwanta district health administration. DESIGN/METHODOLOGY/APPROACH: This is a qualitative study using data from individual and group interviews through purposive selection of health officials, who were directly involved in the work of actual implementation of the programme. Specifically, participants included senior management, middle management and junior workers, who had worked at least for the past three months in the district. FINDINGS: The study found that most of the interviewees involved in the implementation process are knowledgeable of the objectives of the decentralisation process. Also, major factors that are militating against effective decentralisation in the district include inadequate funds, lack of qualified personnel, inadequate logistics and equipment, poor interpersonal relationships, lack of transparency and a good operational system, lack of incentives to motivate the staff, political interference, poor infrastructure and high rate of illiteracy. ORIGINALITY/VALUE: The findings of this study will help improve the implementation of decentralisation within the health sector in Ghana. The paper provides recommendations, which, if considered for implementation, will help improve the decentralisation process. PMID- 22039661 TI - Culture in community pharmacy organisations: what can we glean from the literature? AB - PURPOSE: The aim of this paper is to report on the findings of a systematic literature review-seeking to elicit existing evidence of the nature of organisational culture in community pharmacy organisations. DESIGN/METHODOLOGY/APPROACH: This review takes a novel approach to systematically identifying and synthesising the peer-reviewed research literature pertaining to organisational culture in this setting, its antecedents and outcomes. FINDINGS: The review provides an overview of the scope of and research methods used in the identified literature, together with a narrative synthesis of its findings, framed within five dimensions of organisational culture: the professional business role dichotomy; workload, management style, social support and autonomy; professional culture; attitudes to change and innovation; and entrepreneurial orientation. RESEARCH LIMITATIONS/IMPLICATIONS: There is a need for more detailed and holistic exploration of organisational culture in community pharmacy, using a greater diversity of research methods and a greater focus on patient-related outcomes. ORIGINALITY/VALUE: This paper demonstrates that, whilst little research has explicitly investigated organisational culture in this context, there exists a range of evidence describing aspects of that culture, some of the environmental and organisational factors helping to shape it, and its impact on the pharmacy workforce, services delivered and business outcomes. It highlights the importance of the business-professional role dichotomy in community pharmacy; the influence of individual pharmacists' characteristics and organisational setting; and the impact on pharmacists' wellbeing and job satisfaction and the services delivered. It provides less evidence of the impact of organisational culture on the quality and safety of service provision. PMID- 22039662 TI - Surviving multiple obligations through stimulation, autonomy, and variation. AB - PURPOSE: Professionals in academic health centers (AMCs) face multiple obligations, such as those from research, teaching and clinical care. The purpose of this study is to explore and develop an understanding about how well findings generated from two previous studies about the influence of multiple obligations on health care personnel fit those within health care associated with academic institutions. DESIGN/METHODOLOGY/APPROACH: A total of 11 professionals engaged in teaching, research, and clinical work were interviewed. Data from the open-ended interactive interviews were transcribed and compared with findings from the two previous studies, using modified analytic induction. FINDINGS: Work at an AMC can entail balancing three tasks: research, education, and clinical care. These tasks as well as the different employers associated with them can be a source of conflict. For a group of committed professionals, these conflicts were accepted and balanced as long as they experienced stimulus, autonomy, and variation. RESEARCH LIMITATIONS/IMPLICATIONS: Modified analytic induction, an uncommon analysis method, is useful for comparing findings from previous studies in another context and with different subjects. PRACTICAL IMPLICATIONS: Stimulation, autonomy, and variation could play a vital role as driving factors in coping and dealing with the unavoidable presence of multiple obligations in today's health care systems. ORIGINALITY/VALUE: Although AMCs combine clinical care, research, and teaching, the intersection of all three has in contrast not been investigated so thoroughly at the individual level. PMID- 22039663 TI - Project delivery in HIV/AIDS and TB in Southern Africa: the cross-cultural management imperative. AB - PURPOSE: The purpose of this paper is to report the findings of a broad-based study that initially investigated a possible gap in global inputs into the fight against HIV/AIDS and TB co-infection, and outputs in terms of results achieved. It is proposed that such a gap may be hypothesized to be due, at least in part, to inappropriate management regimes within the global health governance structure. The research does not simply question the effectiveness of the management of programs and projects, but rather the inappropriateness resulting from the lack of addressing cross-cultural issues. DESIGN/METHODOLOGY/APPROACH: The factors facilitating or hampering project service delivery were examined, by looking at 12 case studies in Botswana and South Africa. These data were complemented with seven semi-structured interviews with donor organizations and NGOs, conducted in the North. Cultural interactions were investigated by using the concept of "interfaces". FINDINGS: The results suggest that there is a disjuncture between the global and local level that affects project delivery. The main issues hampering project outcomes can be summarized as systemic, structural and cultural. ORIGINALITY/VALUE: The article's main contributions are both theoretical, looking at global project delivery from a cross-cultural management perspective, as well as to development praxis by highlighting the need to focus more critically on cross-cultural management issues within the global health governance structure, and indeed within international development as a whole. PMID- 22039664 TI - [Long-term survival results according to cytogenetic risk in patients with acute myeloid leukemia--singl center experience]. AB - Cytogenetic analysis of leukemic blasts has become a part of the standard diagnosis approach of acute myeloid leukemia patients. Chromosomal aberrations findings separate AML patients into three broad prognostic categories: favorable, intermediate and high risk. We analyzed retrospectively 179 adults with de novo acute myeloid leukemia (AML), younger than 60 years admitted to our Department between January 1999 and April 2009 to evaluate the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, disease free survival (DFS), and overall survival (OS). All patients received similar induction therapy. Median follow-up of 3.8 years for favorable cytogenetic group CR rate was 85%, 3-year DFS was 70% and 3-year OS was 65%, for intermediate group CR rate, 3-year DFS and 3-year OS were respectively: 64%, 43%, and 38%. Among high risk patient CR rate was 40%, 3-year DFS was 24%, 3-year OS was 17%. We conclude that cytogenetics is among the most useful factors in predicting attainment of CR, DFS, and long-term overall survival in adult de novo AML patients younger than 60 years. PMID- 22039665 TI - [The usefulness of severity scoring systems in elderly intensive care unit (ICU) patients with non-traumatic haemorrhagic shock]. AB - Digestive tract acute haemorrhage has been recognized as one of the major risk factors in mortality of surgical patients. A group of 68 elderly ICU patients with non-traumatic haemorrhagic shock (aged 65-95 yrs) was observed. The patients were evaluated according to commonly used severity-of-illness scoring systems: SAPS2, LODS and POSSUM. A retrospective analysis was based on two groups: a) survivors, and b) nonsurvivors. In both groups there was calculated predicted death rate (PDR): on hospital admittance (in SAPS 2 22.3 in survivors vs 34.8 in non-survivors, in LODS 17.4 vs 30.6, respectively), 2 hrs after surgery (in SAPS 2 25.1 in survivors vs 62.3 in non-survivors, in LODS 21.4 vs 57.2, and in POSSUM 61,6 vs 85.4, respectively), and after the first day of ICU treatment (in SAPS 2 35.0 in survivors vs 70.2 in non-survivors, in LODS 32.5 vs 58.2 respectively); p<001. Similarly, numbers of collected points in Therapeutic Intervention Scoring system (TISS-28) were statistically significant between the groups: 36.1 in survivors vs 47.1 in non-survivors, and in TISS-76: 34.0 vs 45.1, respectively p<0.001. The difference was also noticed during collecting points in severity scoring systems: MODS and SOFA; a number of collected points was twice higher when measured after the surgery, than when comparing the MODS and SOFA values, calculated on hospital admittance in non-survivor group. PMID- 22039666 TI - [Use of the percutaneous drainage in the treatment of patients with hepatic abscesses]. AB - AIM OF THE STUDY: The aim of this study was to review our results in managing liver abscess with the use of sonographically-guided percutaneous drainage. MATERIAL AND METHODS: There were 24 patients (including 12 male and 12 female patients) with liver abscesses treated from 1993 to 2009 in our department. Mean age in the male group amounted to 52 (17-70), while in the female group - 60 (46 72). The group of 22 patients (91,6%) were treated with the use of percutaneously inserted "pigtail drain". RESULTS: The group of 22 patients (11 male and 11 female patients) was treated with the use of percutaneous sonographically-guided drainage. Eschericha coli constituted the most common etiological factor isolated from the purulent content. An average drainage time amounted to 9,5 days. Percutaneous drainage proved ineffective only in 4 patients (2 male and 2 female). In 2 of those cases failure was due to recurrent obstruction of the catheter and in remaining 2--due to migration of the drain outside the abscess. 2 of those patients were treated successfully with another sonographically-guided drainage, while 2 patients required open surgical operation. CONCLUSIONS: Percutaneous sonographically-guided drainage together with antimicrobial therapy constitutes valuable method of choice in the management of liver abscess. The technique has small morbidity and complication ratio allowing avoidance of more invasive surgical interventions. PMID- 22039667 TI - [Effectiveness and safety of intra-articular use of hyaluronic acid (Suplasyn) in the treatment of knee osteoarthritis]. AB - Osteoarthritis (OA) is one of the leading causes of disability in the elderly. The changes in the lubricating properties of synovial fluid lead to significant pain and loss of function. Viscosupplemen-tation, in which hyaluronic acid (HA) is injected into the knee joint, has evolved into an important part of our current therapeutic regimen in addressing the patient with knee pain due to OA. Intra-articular HA or hylan have proven to be an effective, safe, and tolerable treatment for symptomatic knee OA. In an effort to limit cardiovascular, gastrointestinal, and renal safety concerns with COX-2 selective and nonselective NSAIDs and maximize HA efficacy, it is even proposed using HA earlier in the treatment paradigm for knee OA and also as part of a comprehensive treatment strategy. Our study reconfirmed effectiveness and safety of intra-articular use of hyaluronic acid (Suplasyn) in the treatment of knee osteoarthritis. PMID- 22039668 TI - [Thyroid dysfunctions in children with chronic hepatitis C during interferon alpha-2b therapy]. AB - Thyroid dysfunctions are the most frequently described extrahepatic syndromes which complicate HCV infection. Application of interferon in the treatment of chronic hepatitis C increases the frequency their occurrence. The aim of this study was analysis of the frequency of thyroid dysfunctions in children with chronic hepatitis C treated with recombined and pegylated interferon alpha-2b. The study was comprised of 50 children (19 girls, 31 boys) aged from 4 years to 18 years (average 14 years and 6 months) with chronic hepatitis C. Thirty children were treated with recombined interferon alpha-2b and ribavirin, while twenty children received the pegylated interferon alpha-2b and ribavirin. In all children the concentration of thyroid hormones: TSH, fT3 and fT4; as well as the concentration of thyroid antibodies: anty-TG and anty-TPO were examined before beginning of treatment and immediately on its completion. The control group was comprised of 25 children (13 girls, 12 boys) aged from 5 years to 18 years (average 13 years and 6 months) with no observed diseases of liver or thyroid gland. The conducted examinations did not reveal any significant difference in frequency of abnormal concentration occurrence of TSH and fT4 in children with chronic hepatitis C in relation to the control group (respectively: 34% and 20%). However, an abnormal concentration of fT3 was more frequently observed in children infected with HCV, but the average values of this hormone concentration did not significantly differ in both analysed groups of children (respectively: 3.8112 pg/ml and 3.8012 pg/ml). The combined treatment of interferon alpha and ribavirin did not influence more frequent occurrences of abnormal thyroid hormone concentrations, in comparison to their values before treatment. Clinical symptoms of thyroid dysfunction did not accompany the incorrect concentrations of thyroid hormones. Before the treatment, incresed concentration of antithyroid antibodies was observed in a similar percentage of the HCV infected children, as of the healthy children (respectively: 8 and 12%). However, in the group treated with ribavirin and interferon alpha, and especially its pegylated form, the increased concentration of antithyroid antibodies was frequently observed (32% children). The abnormal values of antithyroid antibodies appeared more frequently in girls (10/16). The conducted examinations showed frequent appearance of abnormal values of thyroid hormones and antithyroid antibodies, which indicates the necessity of a systematic control of thyroid gland function in children with chronic hepatitis C treated with interferonem alpha. PMID- 22039669 TI - The prevalence rate of overweight and obesity among adult patient population in Poland, according to the LIPIDOGRAM2004 and LIPIDOGRAM2006 studies, in context of previous Polish national screening surveys. AB - An increase of the body mass often aggravates cardiovascular risk factors. In Poland, over the past 25 years, some epidemiological studies, focused on body mass disorders were conducted. Their results suggest an increase of the prevalence rate of overweight and obesity. The goal of the studies LIPIDOGRAM2004 and LIPIDOGRAM2006 was to assess the prevalence rate of abnormal body mass among adult patients remaining under the care of family physicians in Poland. 17.065 patients in 2004 and 17.152 in 2006, older than 30 years, recruited by 675 study physicians in 444 sites across Poland, were involved into these studies. It was found that approximately 3/4 of the patients included into these studies had BMI > or = 25 kg/m2. Overweight rate was much more prevalent among men than women (48,0% vs. 39,2% in 2004, p<0,0001; 47,4% vs. 39,7% in 2006, p<0,0001). In 2004, obesity was present in above 30% of the participants, including small, but statistically significant difference in the population of men (32,8% vs. 31,2%, p<0,05). In 2006, an increase in the prevalence of obesity in men, compared to women was reported (34,7% vs. 31,6%, p<0,001). Health care actions aimed at decreasing these phenomena would require targeted efforts of family physicians, in collaboration with a multidisciplinary team of specialists. PMID- 22039670 TI - [Plasma cell leukemia: a highly aggressive monoclonal gammopathy with a very poor prognosis]. AB - Plasma cell leukemia (PCL) is an aggressive variant of multiple myeloma and is characterized by the presence of greater then 20% absolute number of plasma cells circulating in the peripheral blood. PCL represents approximately 2-4% of all MM diagnosis and exists in two forms: primary PCL (PPCL, 60% of cases) presents de novo; whereas secondary PCL (SPCL, accounts for the remaining 40%) consists of a leukemic transformation in patients with a previously diagnosed MM. Because the mechanisms contributing to the pathogenesis of PCL are not fully understood, immunophenotyping, genetic evaluation (conventional karyotype, FISH, GEP and array-CGH), and immunohistochemistry are very important tools to investigate why plasma cells escape from bone marrow and become highly aggressive. Since treatment with standard agents and steroids is poorly effective, a combination of new drugs as part of the induction regimens and haematopoietic stem cell transplantation (autologous and allogeneic approaches) may overcome the poor prognosis exhibited by PCL patients. PMID- 22039671 TI - [Serum amyloid A (SAA) as a diagnostic marker in periodontal diseases]. AB - The contemporary knowledge of serum amyloid A (SAA) as a diagnostic marker in periodontal diseases was presented on the basis of the chosen literature. PMID- 22039672 TI - [Placenta endocrine function influence on fetal hypothalamo-hypophyseo-thyroid axis]. AB - The conteporary views on the influence of placenta on the fetal hypothalamo hypophyseo-thyroid axis has been given. The role of hCG, estrogens, deiodineses, transfereses and arylosulphateses has been presented. Transthyretin role has been mentioned. PMID- 22039673 TI - [Taurine chloramine and its potential therapeutical application]. AB - Taurine chloramine (TauCl) is generated at the site of inflammation as a result of reaction of taurine with hypochlorous acid (HOCl), the product of myeloperoxidase-halide system of neutrophils. It has been shown in vitro that TauCl exerts both anti-inflammatory and anti-microbial properties. This review is an attempt to summarize the recent clinical studies in which TauCl was used for local treatment of infectious and inflammatory diseases. PMID- 22039674 TI - [Atypical clinical presentation of autoimmune polyglandular syndrome type 4]. AB - Autoimmune polyglandular syndromes (APS) are rarely diagnosed conditions characterised by the combination of two or more autoimmune endocrinopathies and nonendocrine autoimmunopathies. They comprise a wide spectrum of autoimmune disorders, differing in the immunologic features of their pathogenesis. Based on their clinical manifestation, APS are divided into four different types. Primary hypoparathyroidism is characteristic for APS type 1, the major disease components of which are adrenal insufficiency, hypoparathyroidism, and candidiasis. However, the literature is sparse regarding the presence of hypoparathyroidism in the remaining types of APS. In our article, we present a case of a young female with primary hypoparathyroidism and a family history of autoimmune disorders who after several years developed type 1 diabetes. She also had anti-transglutaminase and anti-parietal cell antibodies. This constellation of two endocrine disorders and non-endocrine abnormalities led to the diagnosis of APS type 4. We show in details diagnostic and treatment strategies undertaken in our patient and their impact on the course of APS. PMID- 22039675 TI - Reinventing the "sick house". PMID- 22039676 TI - Hotel management. PMID- 22039677 TI - Not your grandmother's auxiliary. PMID- 22039678 TI - Body and soul. PMID- 22039679 TI - The futurist: a conversation with Minnesota's Chief Hospital Executive. Interview by Carmen Peota. PMID- 22039680 TI - Slowing the revolving door: Minnesota's hospitals are leading the way in reducing preventable readmissions. PMID- 22039681 TI - A turning point: an experience in the ICU leads a medical student to shift her focus. PMID- 22039682 TI - Critical access hospitals: hubs for rural health care. AB - A 1997 federal law created a new type of rural hospital called the Critical Access Hospital (CAH). Having CAH designation allows a facility to receive cost based reimbursement from Medicare in exchange for providing services such as emergency care and limiting the number of beds and the average length of stay. Minnesota has 79 CAHs. This article describes how having the designation has allowed these facilities to better meet the needs of the populations they serve. It also describes the challenges all CAHs face in light of federal budget constraints and health care reform. PMID- 22039683 TI - The role of the long-term acute care hospital. AB - Long-term acute care hospitals (LTACHs) have a niche role in the health care system. They specialize in caring for patients who are ventilator-dependent, are on inpatient dialysis, or have multi-organ or multi-system failure, postsurgical or organ transplant complications, complex wounds that need care, or traumatic or acquired brain injury. Many physicians are unfamiliar with the work done by the interdisciplinary teams that serve these facilities.This article describes LTACHs and their approach to care. PMID- 22039684 TI - Hyperbaric oxygen for treatment of problem wounds. AB - Hyperbaric oxygen treatment has seen a resurgence of interest in recent years, with more academic medical centers building facilities and more physicians becoming board-certified in undersea and hyperbaric medicine.The reason for the growing interest is better understanding of the role of hypoxia in wound healing and an appreciation for the role of HBOT in reversing tissue hypoxia and enhancing the healing process.This has resulted in a number of new evidence-based indications for HBOT. This article describes the role of HBOT in wound healing and how it specifically applies to treatment of delayed radiation injury, one of the conditions for which it is commonly used. PMID- 22039685 TI - Philanthropy and scientific medicine: the history of the University of Minnesota's Cancer Institute. AB - The University of Minnesota's Cancer Institute was established in 1925 with a gift from the Citizens Aid Society. The Institute was the first cancer hospital in Minnesota, and its focus on patient care, research, and education laid the foundation for the eventual formation of the Masonic Cancer Center. This article describes the origins of interdisciplinary cancer care at the University of Minnesota. PMID- 22039686 TI - Reflections of the PAST while looking to the FUTURE. PMID- 22039687 TI - Facial piercings: do children prefer a dental assistant with or without them? PMID- 22039688 TI - Being green is fabulous in the office and at home. PMID- 22039689 TI - Under pressure. PMID- 22039690 TI - Clinical techniques of performing suctioning tasks and of positioning the high volume evacuation (HVE) attachment and inlet when assisting a dentist. A guide for dental assistants: Part 1. AB - When assisting a dentist, an assistant may need to hold the high volume evacuation (HVE) attachment and use it to suction aerosols produced by the dentist's tools, particularly the high speed hand piece or the cavitron. The main objective of suctioning is to hold the inlet of the HVE attachment close enough to the source of aerosols to evacuate those aerosols, while avoiding suctioning of the patient's intra-oral soft tissues, and avoiding contact of the HVE attachment with the hand piece, cavitron or other instrument that the dentist is using. In general, assisting a dentist with suctioning is a somewhat complex skill that may require months of experience before an assistant develops an intuition for suctioning. This is the first part of a two-part article. The first part describes the basic concepts and clinical techniques that an assistant should be conscious of in order to be able to properly assist a dentist in performing evacuation tasks, describes retraction techniques for use while suctioning, and describes use of the saliva ejector and surgical suction attachment. PMID- 22039691 TI - Streamlining safety and efficiency. PMID- 22039692 TI - [Clinical forensic examination findings and legal outcome in cases of suspected physical child abuse]. AB - Clinical forensic examinations performed at the Institute of Legal Medicine of the Hanover Medical School between 1999 and 2008 in cases of suspected physical abuse of children were analyzed retrospectively with special emphasis on the legal consequences. Altogether, 192 children (85 girls, 107 boys) with a median age of 4.4 years were examined. In 47 cases (24.5 %), the clinical forensic examination findings were interpreted as accidental injuries, birth traumas or unspecific findings. 29 victims (20.0 %) had suffered a shaken baby syndrome. Only part of the presented cases ended with conviction, which was more likely if the victims were aged between 7 and 11 years. Prison terms of 2 years and more were imposed only if the child suffered potentially or acute life-threatening injuries or if additional anogenital lesions were diagnosed indicating sexual child abuse. PMID- 22039693 TI - [Autoerotic fatalities in Greater Dusseldorf]. AB - Autoerotic fatalities in the Greater Dusseldorf area correspond to the relevant medicolegal literature. Our results included exclusively young to middle-aged, usually single men who were found dead in their city apartments. Clothing and devices used showed a great variety. Women's or fetish clothing and complex shackling or hanging devices were disproportionately frequent. In most cases, death occurred due to hanging or ligature strangulation. There was no increased incidence of underlying psychiatric disorders. In most of the deceased no or at least no remarkable alcohol intoxication was found. Occasionally, it may be difficult to reliably differentiate autoerotic accidents, accidents occurring in connection with practices of bondage & discipline, dominance & submission (BDSM) from natural death, suicide or homicide. PMID- 22039694 TI - [From alcohol to liquid ecstasy (GHB)--a survey of old and modern knockout agents. Part 1: historic and classic knockout agents]. AB - Alcohol has been the most important knockout drug in history and literature and continues to play an essential role up to now. Blunt force to the head in the form of a knockout punch is another mechanism leading to a transient loss of consciousness. Diethyl ether and chloroform are among the classical knockout substances. Although they have meanwhile been replaced by modern sedatives and hypnotics, their use is still observed in isolated cases. PMID- 22039695 TI - [Suicide by hypothermia with intentional partial undressing]. AB - Most cases of fatal hypothermia are accidental, often in connection with alcoholisation, homelessness, age-related confusedness and others. The phenomenon of paradoxical undressing may be observed. A paradoxical feeling of warmth in the advanced condition of hypothermia leads to the behaviour of undressing, partly or completely. Suicides with intentional hypothermia are rare. Fatal hypothermia often appears as a concomitant mechanism, e. g. in drug poisoning. The case report describes the fatality of a young woman dying from suicidal hypothermia. She was found partly undressed. This was part of her scheduled plan and not a consequence of paradoxical undressing. PMID- 22039696 TI - [Aiming at the chest, but hitting the back]. AB - Gunshot injuries in the back may suggest the unjustified use of firearms. A wound in the back inflicted by a firearm should not automatically imply that the shooter aimed at the back. A previous study demonstrated that it is possible for men to turn their trunk faster than it takes for a shooter to fire or throw a hand-operated weapon. With a high speed motion camera the authors were able to demonstrate that it is also possible for women to turn their trunk fast enough, so that a shot in the back could have been aimed at the front of the body. This conclusion is also likely to apply to hand-operated or thrown weapons, since the velocity of their projectiles is considerably lower than that of firearms. PMID- 22039697 TI - [Bumping into a knife--exculpatory statement or (tragic) accident?]. AB - Assessing stab wounds is a common task in forensic medicine. Quite often an accused claims that the victim bumped into the knife. Taking into account all the facts ascertained in the investigations conducted, such a statement can be rapidly disproved in most cases. The present case of a 14-year-old boy fatally wounded by his mother with a kitchen knife examines the aspect of walking into a knife. It is an example that this statement cannot always be regarded as implausible and that every single case has to be reconstructed in detail on the basis of all the investigation results. PMID- 22039698 TI - [Application of the hexagon-OBTI test and the RSID blood test for the determination of the post-mortem interval of bone samples]. AB - In this serial experiment, five human bones with known post-mortem intervals (PMI) in a soil environment from five different epochs (0.2 to approximately 2000 years) were tested in a blind setup with two established rapid tests for the identification of human blood traces (Hexagon-OBTI test and RSID blood test). Based on previous study results concerning the usability of the Luminol test for the first assessment of the PMI of osseous remains, the question arising was whether those test procedures, which are highly sensitive for the detection of human blood components, could also be used to narrow down the post-mortem interval. Five test series were conducted applying modified standard protocols of the manufactures. The aim was to find out whether with prior reaction steps or a prolonged time of incubation hemoglobin or its metabolites can be dissolved from the bone and positive test results can be achieved dependent on the PMI. Four test series yielded negative results for all bone samples and one test series a uniformly weak positive result. The results indicate that rapid tests based on the detection of blood are not suitable for the determination of the PMI of bone samples despite the modification of the standard protocols. Further thorough research is required to clarify the postmortem degradation of hemoglobin in bones. PMID- 22039699 TI - [Survived stab to the heart in a schizophrenic man]. AB - Schizophrenia is associated with a significant risk of suicide. According to recent research, 10-15 % of all schizophrenic patients die by suicide. It is not uncommon that the victims show sharp force injuries, so that the forensic pathologist first has to differentiate between self-infliction and involvement of another person. The authors' case report presents a 68-year-old schizophrenic patient who committed suicide by jumping out of a window of his apartment located on the second floor after inflicting multiple stab wounds to his thoracic region. At autopsy, an older stab wound to the apex of the heart was detected. In the criminal investigation, a suicide attempt made 13 days before could be ascertained. As the patient did not want to be taken to a hospital at that time, the injury had never been examined or documented. Since there was no evidence suggesting homicide, the older stab to the heart was interpreted as a tentative injury. PMID- 22039700 TI - [Advances in molecular genetics and treatment of gliomas]. AB - Malignant gliomas are histologically and clinically heterogeneous tumors carrying a poor prognosis despite surgery, radiotherapy and chemotherapy. Recent molecular genetic studies have led to the classification of gliomas into distinct biological entities with prognostic significance, and to the identification of new therapeutic targets. Advances in our knowledge of gliomagenesis and the biological bases of chemoresistance hold promise for improved patient management. We are entering a new era in which individualized and targeted treatment (antiangiogenic therapy, signaling pathway inhibitors) will become increasingly important, in conculsion with conventional treatments and guided by plasma and tumor biomarkers. PMID- 22039701 TI - [Mathematical modeling of low-grade glioma]. AB - Magnetic resonance imaging can be used to quantify low-grade glioma growth with millimetric accuracy. Mathematical modeling helps to analyze individual glioma growth curves and tumor dynamics. Here we focus on the most extensively studied model, based on a proliferation-diffusion equation. We examine how this model offers a new quantitative approach to the natural history of low-grade glioma, including tumor kinetics and other well-known prognostic factors. This approach, based on quantitative imaging coupled with mathematical modeling, has the potential to help optimize treatment strategies. PMID- 22039702 TI - [Update on surgery for diffuse low-grade gliomas: brain mapping, hodotopy and neuroplasticity]. AB - A better understanding of the natural history of diffuse low-grade gliomas (DLGG) and of their interaction with the mechanisms of reactive brain plasticity has led to a switch from a "wait and see" attitude to active therapeutic management. Advances in functional mapping techniques, both preoperatively (neuroimaging) and intraoperatively (awake surgery), have challenged the classical static and localizationist view of brain organization, in favor of a hodotopical model of parallel cortico-subcortical distributed and dynamic networks capable of compensating for one another. Early radical surgical resection is currently the first-line treatment for DLGG, because it delays anaplastic transformation and significantly increases median survival. It also preserves and may improve quality of life, even in patients whose gliomas involve eloquent areas, that were previously considered unresectable. PMID- 22039703 TI - [Genetics and pathophysiology of systemic sclerosis]. AB - Systemic sclerosis (SSc) is a connective tissue disease characterized by early generalized microangiopathy, immunological disorders, and massive overproduction and accumulation of collagen and other matrix components in connective tissue. Although rare, SSc may be considered as is the most severe connective tissue disorder and a major medical challenge. Molecular biology has led to notable progress into genetic predisposing factors and the complex pathogenesis of SSc. Large scale studies have revealed robust genetic associations with severalfactors involved in autoimmunity, while associations with vascular and fibrotic factors are weaker or have not been independently replicated The major histocompatibility complex genes are the most important genomic region in many autoimmune disorders, including SSc. Candidate-gene and genome-wide studies point to a key role of genes encoding proteins involved in innate and adaptive immunity Interactions between genes and environmental factors need to be further investigated. Improvements in diagnostic and prognostic tools are anticipated in the near future, together with more specific immune therapy for these patients, for whom specific treatment is not currently available. PMID- 22039704 TI - [Primary scleroderma myocardial disease]. AB - "Primary" myocardial disease is common in patients with systemic sclerosis and appears to be a factor of poor prognosis when clinically evident. An increasing body of evidence suggests that myocardial involvement is due, at least in part, to abnormal vasospasm, with or without associated structural abnormalities, of the small coronary arteries or arterioles. Impaired myocardial perfusion, as well as left and right ventricular dysfunction, have recently been confirmed in this setting, using more sensitive techniques such as tissue Doppler echocardiography and magnetic resonance imaging. Vasodilators such as calcium channel blockers, angiotensin-converting-enzyme inhibitors and an endothelin receptor antagonist improve both myocardial perfusion and functional abnormalities, and their systematic long-term administration might help to prevent these major complications. PMID- 22039705 TI - [Pulmonary involvement in systemic scleroderma]. AB - Pulmonary involvement in progressive systemic sclerosis can affect either the parenchyma or the vasculature. Both forms are fatal within a few months or years, due to respiratory and/or cardiac failure. Patients must be screened for pulmonary hypertension by ultrasonography, to be confirmed by right heart catheterization if necessary, as early diagnosis and immediate treatment improves the prognosis. The interstitial pulmonary disease progresses slowly, leading to respiratory failure, secondary pulmonary hypertension, and heart failure. Immunosuppressive treatments are disappointing but if prescribed early may prevent or delay the otherwise ineluctable aggravation. Pulmonary involvement threatens the vital and functional prognosis of patients with scleroderma, who may also develop several other complica- tions (especially infections and adverse effects of drugs) that are not dealt with here. This paper focuses on the most significant disease manifestations and current therapeutic options. PMID- 22039706 TI - [Cancer of the esophagus and gastroesophageal junction: evolution of surgical management]. AB - Management of esophageal cancer has evolvedmarkedly in the last two decades. Advances in neoadjuvant treatment combined with refinements in surgical techniques and perioperative care have resulted in better postoperative outcomes and long-term survival. We investigated trends in the outcome of esophagectomy for esophageal cancer over the past 20 years at our high-volume institution. We studied patients who underwent surgery for primary cancer of the esophagus or gastroesophageal junction from 1988 through 2008 (N = 1153). Four study periods (P) were compared: 1988-1993 (P1), 1994-1998 (P2), 1999-2003 (P3) and 2004-2008 (P4). Demographic parameters, tumor characteristics, post-operative morbidity, in hospital mortality and long-term survival were recorded prospectively and the four periods were compared retrospectively. Squamous cell carcinoma accountedfor 77.4% of the 1153 malignancies. The ratio of squamous cell carcinoma to adenocarcinoma fell from 12.0 to 1.3 during the study period (P1 vs P4, P < 0.001), with aparallel increase in the number tumors of the lower esophagus or gastroesophageal junction. The post-operative mortality and morbidity rates were respectively 5.6% and 42.7% overall and remained stable during the study period. The five-year survival rate among all resected patients improved significantly, from 24.3% to 42.7% (P1 vs P4, P< 0.001). The complete (RO) resection rate was 80.7% overall and increased from 74.1% to 82.1% (P1 vs P4, P < 0.05). The five year survival rate improved significantly among RO-resected patients, from 32.7 % to 52.3 % (PI vs P4, P<.0001). The proportion of patients who received neoadjuvant treatment (mainly chemoradiotherapy) rose from 46.8% to 66.5%. The completeness of the pathologic response after neoadjuvant chemoradiotherapy correlated with long-term survival (P < 0.001): five-year survival rates among pathologically complete, partial and non responders were 52.1%, 24.8% and 10%, respectively. Short-term outcomes after resection remained stable during the study period and comparedfavorably with those reported by other high-volume institutions. Long-term survival improved significantly. Advances in staging methods andsurgical management, combined with more stringent patient selection and use of neoadjuvant chemoradiation, may explain this progress. More reliable predictors of complete RO resection and of the response to chemoradiation therapy are needed in order to tailor management to the individual patient. PMID- 22039707 TI - [Keratoconus, the most common corneal dystrophy. Can keratoplasty be avoided?]. AB - Keratoconus is the most common form of corneal dystrophy. It consists of a non inflammatory progressive thinning process that leads to conical ectasia of the cornea, causing high myopia and astigmatism. In more advanced cases, opacities can be seen at the apex of the cone. Traditional conservative management of keratoconus begins with spectacle correction and contact lenses. Surgery is recommended when a stable contact lens fit fails to provide adequate vision. Keratoplasty was long the only surgical treatment, but recent years have seen the introduction of new surgical options:--Collagen cross-linking stiffens the cornea and can halt disease progression;--Intrastromal corneal rings can reduce astigmatism and improve visual acuity;--Intraocular lenses are valuable additional options for the correction of refractive errors. Currently, keratoplasty is mainly restricted to patients with opacities of the central cornea. PMID- 22039708 TI - [Basic surgical training in 2010]. AB - Initial surgical training must take into account the major changes that have taken place in recent years. Training in surgical technique, clinical expertise, communication skills, clinical and experimental surgical research, team work and risk management is required to maintain the leadership position of future surgeons. PMID- 22039709 TI - [Type 1 diabetes impairs compensatory response after myocardial infarction; role of tissue hypothyroidism and effects of thyroid hormone administration]. AB - Type 1 diabetes (TOD) increases the risk of coronary artery disease and myocardial infarction and is characterized by baseline cardiac dysfunction. We investigated the influence of TOD in post-infarct remodeling (REM) and the role of thyroid hormone (TH) signaling in this response. Acute myocardial infarction (AMI) was induced in rats with type I diabetes (TOD) and in non diabetic rats (NTOD-AMI), sham-operated rats serving as controls (SHAM). AMI resulted in tissue hypothyroidism due to significant downregulation of the TH receptors TRa1 and TRbeta1 in the TOD myocardium, while no change in plasma T3 or T4 was observed This response was associated with increased expression of beta-MHC and distinct changes in cardiac function and geometry: EF % was decreased in TOD-AMI as compared to NTOD-AMI. Systolic and diastolic chamber dimensions were increased, with no concomitant increase in wall thickness. Thus, WTI (the ratio of LVIDd/2 x posterior wall thickness), an index of wall stress, was significantly increased in TOD-AMI. The absence of wall thickening in TOD-AMI hearts was associated with changes in stretch-induced kinase hypertrophic signaling: phosporylated (p) ERK and p-p38 MAPK levels were not changed in TOD-AMI in comparison with non infarcted hearts (TOD-SHAM) and NTOD-A MI hearts. TH administration after AMI prevented tissue hypothyroidism and resulted in decreased beta-MHC expression, increased wall thickening and normalized wallstress, while stretch-induced p38 MAPK activation was increased. We conclude that diabetes exacerbates post ischemic cardiac remodeling and that tissue hypothyroidism may be involved in this response. PMID- 22039710 TI - [Streamlining of medical orders in an intensive care unit]. AB - OBJECTIVES: To We assessed whether intensivists ICU physician acceptance of a system designed to would accept to optimise e their orders for ings of biological samplesings, X-rays and target drugs, and to assess the consequences of this rationalization for on patient's outcome. STUDY DESIGN: Monocentric evaluation of medical economic procedure. The medical ordering process started to be assessed in our ICU in late 2006, METHODS: Mat meetings of consultants, registrars and residents, held started on Dec. 21, 2006 with 2-3 2 or 3 times a year sessions a year in order to evaluate the process of medical ordering. The p Physicians and pharmacists provided ordering data at each meeting Orderings of routine samplesings, bedside X-rays and unjustified expansive costly drugs were was discouraged, while targeted sampling ings and lung chest ultrasonography were encouraged. New residents were systematically taught about informed of the this programme. Meanwhile m Monthly morbidity-mortality meetings were pursued in order to assess the consequences impact of this politicspolicy. RESULTS: While Although ICU total ICU activity increased by 3.4%, and potentially evitable avoidable deaths decreased fell by 34%, % and annual expenses decreased dropped by approximatively about 777 750 000 euros from 2006 to 2008. This cost saving was due to decreased orderings fewer orders in for biological samples y by (-30%), bedside X-rays by (-10%), computed tomographic scans computed tomography by ( 16%) and target drugs? by (-35%). However, an increased ordering in use of 4 target drugs was increased observed in between 2008 as compared with 2007 and 2008. CONCLUSION: Multidisciplinary optimisation of medical ordering can thus be efficient effective in an in ICU, although. However a profit-sharing with ordering physicians would be necessary to might help to prolong the system. PMID- 22039711 TI - [Mediterranean visceral leishmaniasis]. AB - Mediterranean visceral leishmaniasis is a parasitic zoonosis due to Leishmania infantum. The dog is the reservoir species and also the main victim. The vector is the female Phlebotomus sand fly. In the southern Mediterranean region the disease is most frequent in children, whereas in Europe, and particularly in France, it is mostly an opportunistic infection associated with immunosuppression. Frequent asymptomatic carriage has been detected in southern Europe. The classic symptom triad consists of fever, pallor and splenomegaly. Biological signs include low cell blood counts (anemia, leukoneutropenia, and thrombocytopenia) and an inflammatory syndrome. Commercial serologic tests such as those based on immunoblotting are very useful. The gold standard for diagnosis is parasite detection in bone marrow or blood. PCR is useful for therapeutic follow-up. Treatment is currently based on liposomal amphotericin B (AmBisome). PMID- 22039712 TI - [Pregnant women's oral hygiene knowledge and habits after the second millennium in South-East Hungary]. AB - Among the predisposing agents for inflammatory periodontal lesion dental plaque is the most important, but different local and systemic factors may influence the seriousness or progression of periodontitis. Hormonal changes during pregnancy belong to the systemic aggravating factors. The aim of the present study was to assess pregnant women's oral hygiene knowledge and habits, and if these have a relationship with age, residence, educational level and profession/occupation. Questionnaires were used for the data collection. 275 pregnant women, who underwent prenatal care at the Department of Obstetrics and Gynecology in Szeged, volunteered to answer the questions. The results showed that almost all the women brushed their teeth daily, but only about one third of them used special oral hygiene tools, like dental floss. Many of the women claimed to have gingival bleeding when brushing their teeth. More then 70% visited a dentist during pregnancy. There was a significant relationship between educational level and the use of dental floss (p=0.004) and gingival bleeding (p=0.023) Oral hygiene education, dental and periodontal treatment of pregnant women need more emphasis during prenatal care. PMID- 22039713 TI - [Restoration of profound tooth damage caused by intrinsic erosion, with porcelain crowns. A case report]. AB - In the presented case extensive tooth damage has been caused by an eating disorder (bulimia nervosa coupled with frequent vomiting). Although the patient's premised disorder has been treated successfully, palatal and occlusal surfaces of the upper teeth were profoundly damaged due to previous acidic erosion. There was also a significant hypersensitivity of upper teeth, and the patient was dissatisfied with the aesthetics of the upper teeth as well. In order to treat pain symptom, replace lost hard dental tissues, and restore aesthetics, porcelain covered zirconium dioxide crowns of upper teeth were prepared. Tooth hypersensitivity disappeared as a result of the insertion of crowns following a careful minimal-invasive preparation. Patient's high aesthetic needs were also fulfilled by using high quality materials. At the 6-months-follow-up examination disappearance of tooth sensitivity and satisfaction with the aesthetics were reported by the patient. Long run gingival and mucosal health as well as proper condition of dental hard tissues and dentures were determined by the intraoral control examination. The patient also presented high level of oral hygiene. PMID- 22039714 TI - [Possible correlations between periodontitis and chronic obstructive pulmonary disease. Review of the literature]. AB - Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial inflammatory disease of the airways and the pulmonary parenchyme, caused by infection, air pollution and particles. 4-7% of the adult population is involved. COPD is the 4th-6th common cause of death throughout the world. The main aetiological factor is smoking. Bacteria, such as bacteria from the oral cavity, could play a keyrole in the progression of the disease. Epidemiologic studies have noted a relationship between poor oral hygiene or periodontal bone loss and chronic obstructive pulmonary disease. The prevalence and mortality of the disease is increasing worldwide, the treatment is expensive, the efficiency of the present pharmacotherapy is poor, so the importance of prevention should be increasing. Patients with chronic obstructive pulmonary disease (COPD) are prone to frequent exacerbations which are a significant cause of morbidity and mortality. This review is a short summary of studies about the possible relationship between periodontitis and COPD. PMID- 22039715 TI - [Diagnosis of masticatory organ dysfunction craniomandibular system dysfunction (CMD)]. AB - A practising dentist often meets pains of different location and limited ability of mouth opening, locomotor disorder, the cause of which is difficult to identify and explain. There is a particular group of patients with functional disorder who turn to several doctors with their varied and colorful symptoms. Most of these patients suffer from cranio-mandibular disfunction (CMD). You must not indicate any treatment especially not an invasive one without a diagnosis. While relieving the patient's pains, you have to determine the cause and effect. The authors suggest discussing the issue of giving a unanimous definition of masticatory organ disfunction as an interdisciplinary diagnosis which is in accord with international bibliography. They review the algorithm of diagnosis, indication of medical examination by demonstrating some typical cases. They share their experience gained during several decades of clinical practise involving about 2,000 patients. PMID- 22039716 TI - [Alzheimer: destiny of a disease]. PMID- 22039717 TI - [Is anonymous childbirth a sustainable option?]. PMID- 22039718 TI - [Segond fracture]. PMID- 22039719 TI - [Raynaud's phenomenon, disease or syndrome?]. AB - Raynaud's phenomenon is a common symptom. More often it is usually an idiopathic and benign condition. But it can be an early manifestation of a connective tissue disease especially scleroderma and primary Sjogren's syndrom. Thus it is necessary to develop reasonable screening model. If the vasomotor symptoms are localized, a diagnosis of secondary Raynaud's phenomenon is highly probable and the main etiology is an arterial disease. Occupational arterial lesions are a particularly aspect of secondary Raynaud's phenomenon. Calcium channel blockers are the reference for the symptomatic treatment of Raynaud's phenomenon. In severe secondary forms, intravenous iloprost infusion is effective. New drugs as endothelin antagonist and phospodiesterase type 5 inhibitors are still to be evaluated. PMID- 22039720 TI - [Vocal cord dysfunction]. AB - Vocal cord dysfunction is characterized by paradoxical vocal cord adduction, especially during inspiration. Clinical symptoms can mistakenly lead to a diagnosis of asthma. Some patients, thought to be asthmatic, are sometimes considered as having severe asthma. Positive diagnosis rests on the finding of paradoxical vocal cord adduction on laryngoscopic examination. The main limitation of this examination is associated with the intermittent nature of the symptoms. The diagnosis of vocal cord dysfunction can thus be mistakenly ruled out based on the absence of abnormalities on laryngoscopic examination. Therapeutic management focuses on phoniatric rehabilitation. PMID- 22039721 TI - [Alzheimer's diseases. Even in absence of progress, we must do better!]. PMID- 22039722 TI - [How to define Alzheimer's disease]. AB - Alzheimer's disease, which was considered to be a rare disease in subjects aged under 65 until the seventies/eighties, has become a very common disease affecting mostly older subjects. Many consider that it is important to review the meaning of the eponym "Alzheimer's disease", and a revolution, quite literally, is likely to occur. The role of vascular lesions in the onset of dementias among older subjects is widely acknowledged; considering those dementias as Alzheimer's disease may have negative consequences for patient management. Indeed, vascular lesions can be prevented and treated, while Alzheimer's lesions cannot. It may be justified to use "Alzheimer syndrome" instead of "Alzheimer's disease" when vascular risk factors and, all the more so, vascular lesions are present. Significant progress has been made in the understanding of the pathological proteins involved in Alzheimer's disease, as well as their effects on neurons and synapses. However, the etiology of the disease is still unknown, except in the rare hereditary cases, and there is no cure for Alzheimer's disease at present. Clinical research is progressing, and diagnostic criteria for the pre-dementia stage of Alzheimer's disease were suggested. In France, the outstanding Alzheimer plan 2008-2012 should play an important role in enhancing the understanding of Alzheimer's disease, Alzheimer's syndromes and related disorders. PMID- 22039723 TI - [Epidemiology of Alzheimer's diseases]. PMID- 22039724 TI - [Rethinking Alzheimer's diseases]. PMID- 22039725 TI - [Are Alzheimer's diseases dementia?]. PMID- 22039726 TI - [Genetics of Alzheimer's disease]. PMID- 22039727 TI - [Alzheimer's disease: early diagnosis]. AB - Alzheimers disease and the other forms of dementia are frequently ignored in the general population, particularly after 80 years. This under-diagnosis concerns approximately one of every two patients, and is particularly common in early stage dementia, in which only one of every three patients is diagnosed. Under diagnosis is due to patients and families not consulting, as well as to diagnosis procedures not being performed by the general practitioner to explore cognitive complaint. However, once they have been initiated, the diagnostic procedures are adequately performed, and over-diagnosis is uncommon. PMID- 22039728 TI - [CSF proteins: useful markers in Alzheimer's disease]. PMID- 22039729 TI - [Specific care plan in different stages of Alzheimer's disease]. AB - The management and follow-up of patients with Alzheimers disease have stage specific characteristics. In the mild stage, the key challenges are above all to improve the early diagnosis and the communication of the diagnosis. With the patient's agreement, a follow-up should be scheduled to assess, at each stage of the disease, cognitive and functional decline, and detect psycho-behavioral, nutritional or mobility complications. In the moderate or severe stages, prevention and treatment of caregiver burnout should be included in the follow up. Finally, in the very severe stage, end of life and ethical issues should be considered. The followup and the intervention plan should be adapted to each patient, and require coordination between health care professionals and social workers. However, the practical aspects of the follow-up and the ways in which those can be improved are yet to be defined. PMID- 22039730 TI - [Importance of physical activity in Alzheimer's disease]. PMID- 22039731 TI - [Weight loss in Alzheimer's disease]. PMID- 22039732 TI - [Treatment of behavioral disorders in Alzheimer's disease]. AB - Behavioural and psychological symptoms (BPSD) are now known to be frequently associated to cognitive and functional decline in Alzheimer's disease and related disorders. Recommendations for the management of BPSD have been proposed. Non pharmacological interventions should be the first-line treatment. Anti-dementia agents (cholinesterase inhibitors, memantine) and psychotropic drugs (antipsychotics, antidepressants and anticonvulsivants) could be associated to non-pharmacological interventions only in case of limited response with non pharmacologic approaches. Low-dose antipsychotics should only be prescribed for limited periods of time, in case of psychotic and/or aggressive refractory symptoms. PMID- 22039733 TI - [Non pharmacologic intervention therapy in Alzheimer's disease]. AB - Actually, no curative treatment is available to fight against Alzheimer's disease. Previous non pharmacologic intervention trials had promising findings. However the lack of scientific validation and standardized modelling restrict their use. Among these techniques, sparing skills therapy (SST) seems promising. This form of care is for patients with early stage of the disease and combines the use of cognitive and functional residual, taking into account the wishes of the patient and their caregiver, the rehabilitation of their environment and the education of the caregiver. The SST is developing in France within specialized teams inside the nursing services at home and is currently the subject of further research. PMID- 22039734 TI - [Rights of people with Alzheimer's disease]. AB - Population aging and the increasing prevalence of Alzheimer's disease and related disorders raise the question about the existence of legal tools to protect and maintain patient autonomy. Against this background, it is essential that physicians are aware of the different legal options that allow them to help patients in need. Justice protection (sauvegarde de justice), guardianship (curatelle) and trusteeship (tutelle) are useful tools, but they leave no room for anticipation. While these emergency tools have to be constantly adapted to the condition of the protected adult, they are still imposed. Thus the emergence of a new tool, the future power of attorney (mandat de protection future), asserts the right to foresight, and allows the patient to regain a central position in their future management. PMID- 22039735 TI - [Explosion in PubMed/MEDLINE]. PMID- 22039737 TI - [Approach to urinary incontinence in women]. AB - Urinary incontinence is a very common problem in women; it can lead to a specific alteration of quality of life which is necessary to evaluate before any treatment. Various types of incontinence can be described: stress incontinence, urge incontinence, mixed incontinence. Clinical examination is always necessary to exclude a specific cause of incontinence particularly neurogenic dysfunction in which incontinence may be the first symptom before motor or sensitive alterations appearance. Urodynamic investigations can easily determine pathophysiologic factors and allow a best choice of therapeutic strategies. Concerning stress urinary incontinence, first line treatment consists of pelvic floor exercices before surgical therapy, and anticholinergic drugs are always tried in urge incontinence before sacral neuromodulation. PMID- 22039736 TI - [Epidemiology of female urinary incontinence]. AB - Female urinary incontinence becomes a real public health issue in France, with high frequency and outcomes on 20 to 30% of concerned women. Prevalence of incontinence is widely under-estimated because few women consult a physician for this problem, and because of the lack of epidemiologic data about it. Despite female urinary incontinence will increase in the next future with "baby boom" population, and in spite of new treatments, medical help is not suitable. Physicians but also nurses and physical therapists must have better professional training to help and care better these women. PMID- 22039738 TI - [Urinary incontinence in pregnant women]. PMID- 22039739 TI - [Conservative treatment of female urinary incontinence]. AB - Female urinary incontinence can be improved by nonsurgical pharmacologic as well as non-pharmacologic treatments. Hygiene and dietary rules apply to all forms of incontinence. If overweight, weight loss improves stress urinary incontinence. There are levels of evidence to show that pelvic floor muscle training and behavioral therapy improve incontinence. Duloxetine is better than placebo for improvement of quality of life and for the impression of an improvement, but its place is still not determined in the algorithm of conservative treatments. The effects of vaginal electrostimulation and oestrogen are inconsistent or inhomogeneous. In case of urgency incontinence, anticholinergics remain the first line treatment and the place of stimulation of posterieur tibial nerve is still to be defined. PMID- 22039740 TI - [Obesity and female urinary incontinence]. PMID- 22039741 TI - [Surgical treatment of female urinary stress incontinence]. AB - Since the description of the sub urethral technique for genuine stress incontinence all the others have been abandoned. The surgical indications have not changed and are related to the poor quality of life of the patient induced by stress incontinence. A careful clinical examination and a pre operative urodynamique investigation should prevent from the failures due to a wrong indication. All the techniques are the same when it comes to the result except the mini slings which still have to be evaluated. There are two types of complications: the ones which are specific to the using of a hexogen material by vaginal way and the ones linked to the technique itself. The results are excellent, more than 80% success and last for a long period. PMID- 22039742 TI - [Grand rounds on medical education]. PMID- 22039743 TI - [Food intake, nutritional status and health]. PMID- 22039744 TI - [Diagnosing acute appendicitis]. PMID- 22039745 TI - [Human infertility: management of the first consultation]. PMID- 22039746 TI - [Bacterial and mycotic cutaneomucosal infections]. PMID- 22039747 TI - [Ankylosing spondylitis]. PMID- 22039748 TI - [Follow-up of patients with artificial heart valves]. PMID- 22039749 TI - [Pleural effusion]. PMID- 22039750 TI - [The Fragonard museum of the National Verinary School of Alfort]. PMID- 22039751 TI - Changing individual-level risk factors for malaria with declining transmission in southern Zambia: a cross-sectional study. AB - BACKGROUND: Malaria elimination will require that both symptomatic- and asymptomatic-infected persons be identified and treated. However, well characterized, individual-level risk factors for malaria may not be valid in regions with declining malaria transmission. Changes in individual-level correlates of malaria infection were evaluated over three years in a region of declining malaria transmission in southern Zambia. METHODS: Malaria surveys were conducted in two study areas within the catchment area of Macha Hospital, Zambia in 2007 and 2008/2009. A random sample of households was identified from a digitized satellite image of the study areas. Cross-sectional surveys were conducted approximately five times throughout the year in each of the two study areas. During study visits, adults and caretakers of children were administered questionnaires and a blood sample was obtained for a rapid diagnostic test (RDT) for malaria. RESULTS: In the 2007 study area, 330 individuals were surveyed. 40.9% of participants lived in a household with at least one insecticide-treated bed net (ITN); however, only 45.2% reported sleeping under the ITN. 23.9% of participants were RDT positive. Correlates of RDT positivity included younger age, the presence of symptoms, testing during the rainy season, using an open water source, and not sleeping under an ITN. In the 2008 study area, 435 individuals were surveyed. 77.0% of participants lived in a household with at least one ITN; however, only 56.4% reported sleeping under the ITN. 8.1% of participants were RDT positive. RDT positivity was negatively correlated with the presence of symptoms within the last two weeks but positively correlated with documented fever. In 2009, 716 individuals were surveyed in the same area as 2008. 63.7% of participants lived in a household with at least one ITN; however, only 57.7% reported sleeping under the ITN. 1.5% of participants were RDT positive. Only self-reported fever was significantly correlated with RDT positivity. CONCLUSIONS: With declining malaria prevalence, few individual-level characteristics were correlated with RDT positivity. This lack of correlation with individual characteristics hampers identification of individuals infected with malaria. Strategies based on ecological or environmental risk factors may be needed to target control efforts and achieve further reductions and elimination. PMID- 22039753 TI - Prevalence of antibodies to equine viruses in the Netherlands. AB - Summary The prevalence of antibodies to various viruses was investigated in a series of serum samples collected from horses in the Netherlands between 1963 and 1966 and from 1972 onwards. Neutralizing antibodies to equine rhinopneumonitis virus, equine arteritis virus and to equine rhinovirus types 1 and 2 were detected in respectively 76%, 14%, 66% and 59% of the equine serum samples tested. The observed incidence of serum samples positive to equine adenovirus in the complement fixation test was 39%. Precipitating antibodies to equine infectious anaemia virus were detected only in serum samples from two horses imported from abroad. Haemagglutination inhibiting antibodies to Myxovirus influenzae A / equi-1, M. Influenzae A / equi-2, and Reovirus types 1, 2, and 3 were present in respectively 82%, 50%, 10%, 33% and 3.6% of the serum samples tested. The most frequently observed incidence of antibodies to the various equine respiratory viruses occurred in the groups of horses having repeatedly contact with other horses. PMID- 22039752 TI - Affective reactivity during smoking cessation of never-quitters as compared with that of abstainers, relapsers, and continuing smokers. AB - Much effort has been devoted to examining the differences in postcessation affective experience between smoking abstainers and relapsers. However, little attention has been given to the affective changes of smokers who, despite their motivation to quit, fail to achieve even a brief period of abstinence. Using affect-modulated startle response and self-report questionnaires, we measured the postcessation affective changes of 115 smokers (60 men, 55 women) who participated in a laboratory investigation of affective reactivity during smoking cessation. Among our participants, 34 were abstainers (16 men, 18 women), 16 were never-quitters (8 men, 8 women), 19 were relapsers (8 men, 11 women), and 46 were controls (28 men, 18 women). We found a significant Stimulus Valence * Session * Group interaction effect on startle responses, which suggested that while abstainers, relapsers, and control exhibited the prototypical affect-modulated startle response across postcessation sessions, never-quitters displayed an atypical response pattern in which emotional pictures no longer modulated the startle response. Never-quitters also reported increasingly higher negative and lower positive affect across postcessation sessions. Using affect-modulated startle response and self-report questionnaires, this study found a significant difference in the affective reactivity between smokers who could and smokers who could not establish an initial abstinence of 24 hours. PMID- 22039754 TI - Perilobular fibrosis in chronic bovine fascioliasis. AB - Summary The character, extent, and localization of perilobular fibrosis were studied in cattle experimentally infected with Fasciola hepatica. Such fibrosis is indirectly due to the liver flukes. The regionally localized fibrosis results from cholestasis due to transient occlusion of branches of the biliary tree. In perilobular fibrosis it is possible to distinguish a florid, an intermediate, and an uncomplicated form. The florid phase is marked by proliferation of the biliary epithelium and is followed by infiltration of inflammatory cells. PMID- 22039755 TI - Milk production increase following treatment of Dutch dairy cattle with thiabendazole. AB - Summary In a trial involving 542 dairy cattle on 28 farms, 276 were treated once with thiabendazole within two days of calving. The treated group showed an average increase in milk yielded over the non-return group of 229.8 kg during the subsequent lactation. In the treated group, total milk fat production was increased over that of the controls by 7.4 kg per cow; milk protein was increased by 6.9 kg per cow. All treatment parameter differences were highly significant at the 1% level of probability. PMID- 22039756 TI - Contribution to the aetiology of synovitis in chickens, with special reference to non-infective factors. IV. AB - Summary The comparative study reported in the present paper was undertaken to collect data on the collagen content and collagen quality of tendons showing high (low) tensile strength levels and a compact (loose) histological structure. It was shown that tendon tissues of these two groups do not differ in this regard. The effect of administering a number of nutrients (known to be essential in collagenesis) was tested during this study. Administration of these nutrients did not prevent synovitis and did not increase tensile strength. PMID- 22039757 TI - Some biochemical parameters for qualification of bull semen. AB - Summary Since the macroscopical and microscopical examination of bull semen does not in all cases appear to give conclusive indications concerning the fertilizing capacity, an investigation of some biochemical parameters was undertaken. It was shown that the following biochemical examination could furnish some more information about the quality of the semen: 1. Determination of the phenylalanine- alpha-ketoglutarate transaminase activity both in the seminal plasma and in the whole semen. A high transaminase activity in the plasma points to leakage out of the spermatozoa, thus indicating an affection of the spermatozoa. In that case larger amounts of basic amino acids and of leucine were often found in the seminal plasma than would normally be observed. 2. Gas chromatographic examination of the steroids occurring both in the seminal plasma and in the spermatozoa. In a number of infertile bulls small peaks of progesterone were found together with those of other, unidentified compounds. 3. Investigation of the carbohydrate metabolism in the semen. In a number of fertile bulls the following deviations were found: a. the presence of quite a lot of fructose in the spermatozoa; b. the presence of glucuronic acid and / of other foreign compounds in the spermatozoa or in the plasma; c. an elevated pH in the seminal plasma some 2 to 3 hours after ejaculation; d. a low phenylalanine-alpha -ketoglutarate transaminase activity in the whole semen (the spermatozoa had been disrupted by freezing). 4. Investigation of the presence of reducing aldehydes (glycolaldehyde and glyceraldehyde) inside the spermatozoa. The determinations mentioned under 1, 3c and 3d can easily be carried out in the laboratories of each District Animal Health Service and of the A.I. stations; the same is true of the occurrence of amino acids in the seminal plasma and of fructose and aldehydes inside the spermatozoa if facilities are available for electrophoresis and chromatography. PMID- 22039758 TI - Possible aspects of normal and unphysiological commercial conditions on the estrus and early pregnancy in pigs. AB - Summary Gilts and sows kept under unphysiological commercial conditions may show delayed puberty, delayed estrus postweaning and delayed returns after insemination. It is postulated that in all three manifestations gonadotropic insufficiency is the causative factor, produced by inadequate exteroceptive stimulation, mainly of olfactory origin, or by a configuration of stimuli which is experienced as in-appropriate by the individual organism. Pituitary L.H. is necessary to induce tertiary follicles to secrete estrogens, which play a prominent part in estrus expression and in turn evoke the pre-ovulatory L.H. peak flow. Pituitary L.H. also appears to be necessary for persistence of the corpora lutea during early pregnancy and this L.H. release may also be inhibited under inadequate physiological conditions. Therefore anaphrodisia in big commercial piggeries can be a normal physiologic reaction of the animal and more or less an adaptation to these unfavourable circumstances. For the greater part delayed puberty and delayed estrus postweaning seem to be coupled with anestrus and can easily be overcome by gonadotropin treatment in this case. Resulting fertility can be normal, even under severe stressful conditions. The delayed returns after insemination are partly caused by embryonal mortality. This mortality is at least for a part caused by gonadotropin insufficiency which in future may be prevented by application of a proper treatment as well. PMID- 22039759 TI - The therapy of otitis externa. AB - Summary The clinical findings following the instillation of an aqueous solution containing natamycin, neomycin and hydrocortisone into the ears of dogs exhibiting the signs of otitis externa are described. Out of a total of 143 cases, 50 were also examined microbiologically both before and after treatment in order to evaluate the antibacterial and antifungal properties of the solution. The severity of the complaint appeared to be of little significance as far as the respons is concerned. A favourable response was noted clinically in 95% and microbiologically in 86% of the cases treated. PMID- 22039762 TI - Specific labeling of threonine methyl groups for NMR studies of protein-nucleic acid complexes. AB - Specific (13)C labeling of Thr methyl groups has been accomplished via the growth of a standard laboratory strain of Escherichia coli on [2-(13)C]glycerol in the presence of deuterated isoketovalerate, Ile, and Ala. Diversion of the label from the Thr biosynthetic pathway is suppressed by including Lys, Met, and Ile in the growth medium. This method complements the repertoire of methyl labeling schemes for NMR structural and dynamic studies of proteins and is particularly useful for the study of nucleic acid binding proteins because of the high propensity of Thr residues at protein-DNA and -RNA interfaces. PMID- 22039763 TI - TBX3 over-expression causes mammary gland hyperplasia and increases mammary stem like cells in an inducible transgenic mouse model. AB - BACKGROUND: The T-box transcription factor TBX3 is necessary for early embryonic development and for the normal development of the mammary gland. Homozygous mutations, in mice, are embryonic lethal while heterozygous mutations result in perturbed mammary gland development. In humans, mutations that result in the haploinsufficiency of TBX3 causes Ulnar Mammary Syndrome (UMS) characterized by mammary gland hypoplasia as well as other congenital defects. In addition to its role in mammary gland development, various studies have also supported a role for Tbx3 in breast cancer development. TBX3 is over-expressed in various breast cancer cell lines as well as cancer tissue and has been found to contribute to breast cancer cell migration. Previous studies have suggested that TBX3 contributes to cancer development by its ability to bypass senescence by repressing the expression of p14(ARF)-tumor suppressor. Although many studies have shown that a dysregulation of TBX3 expression may contribute to cancer progression, no direct evidence shows TBX3 causes breast cancer. RESULTS: In this study, we created doxycycline inducible double transgenic mice (MMTV-rtTA;tet-myc TBX3-IRES-Luciferase) to test whether TBX3 over-expression can induce tumor formation within the mammary gland. Although over-expression of TBX3, alone, did not induce tumor formation it did promote accelerated mammary gland development by increasing mammary epithelial cell proliferation. We also show that TBX3 directly binds to and represses NFkappaBIB, an inhibitor of the NF-kappaB pathway known to play a role in regulating cell proliferation. Lastly, we also show that the over-expression of TBX3 is associated with an increase in mammary stem-like cells. CONCLUSIONS: Overall, our data suggests that over-expression of TBX3 may contribute to breast cancer development by promoting accelerated mammary gland development through the inhibition of the NF-kappaB pathway and stimulation of both mammary epithelial cell and stem-like cell proliferation. PMID- 22039764 TI - Polygalacturonase-inhibiting proteins--leucine-rich repeat proteins in plant defence. AB - Plant polygalacturonase-inhibiting proteins (PGIPs) belong to the leucine-rich repeat (LRR) family and are known to prevent pathogen invasion by inhibiting the plant cell wall degrading enzyme, polygalacturonase. Our study reveals that these multigene-encoded defence proteins found in flowering plants only exhibit identical domain architecture with 10 tandemly-arranged LRRs. This implies that variations of PGIP inhibitory properties are not associated with the number of the repeats but with subtle changes in the sequence content of the repeats. The first and eighth repeat contain more mutations compared to the strict conservation of the plant-specific LRRs or any repeat at other positions. Each of these repeats forms a separate cluster in the phylogenetic tree, both within and across plant families, thus suggesting uniqueness with respect to their position. A study of the genes encoding PGIPs, shows the existence of two categories (i) single exon and hence no intron; and (ii) two exons with an intron in between. Analyses of the intron phase and correlation of the exon-intron structure with the compact structural modules in PGIPs support insertion of introns in the pre existing single exon genes and thus the intron late model. Lack of conservation of phase across families and formation of individual clusters for each family in the phylogenetic tree drawn with the intron sequences illustrate the event of insertion that took place separately in each of these families. PMID- 22039765 TI - Electronic and magnetic properties and structural stability of BeO sheet and nanoribbons. AB - The novel electronic and magnetic properties of BeO nanoribbons (BeO NRs) as well as their stability are investigated through extensive density functional theory calculations. Different from semiconducting graphene nanoribbons and insulating BN ribbons, all zigzag edged BeO NRs are revealed to display ferromagnetic and metallic natures independent of the ribbon width and edge passivation. The polarized electron spins in H-passivated zigzag BeO NRs are from the unpaired electrons around the weakly formed Be-H bonds, while those of bare zigzag BeO NRs are due to the 2p states of edge O atoms. In sharp contrast, all armchair BeO NRs are nonmagnetic insulators regardless of the edge passivation. In particular, all bare armchair BeO NRs have a nearly constant band gap due to a peculiar edge localization effect. Interestingly, the band gaps of all armchair BeO NRs can be markedly reduced by an applied transverse electric field and even completely closed at a critical field. The critical electric field required for gap closing decreases with increasing ribbon width, thus the results have practical importance. Further stability analysis shows that bare BeO NRs are more stable than H-passivated BeO NRs of similar ribbon widths and bare armchair BeO NRs are energetically the most favorable among all the nanoribbons. PMID- 22039766 TI - Doc, what would you do if you were me? On self-other discrepancies in medical decision making. AB - Doctors often make decisions for their patients and predict their patients' preferences and decisions to customize advice to their particular situation. We investigated how doctors make decisions about medical treatments for their patients and themselves and how they predict their patients' decisions. We also studied whether these decisions and predictions coincide with the decisions that the patients make for themselves. We document 3 important findings. First, doctors made more conservative decisions for their patients than for themselves (i.e., they more often selected a safer medical treatment). Second, doctors did so even if they accurately predicted that their patients would want a riskier treatment than the one they selected. Doctors, therefore, showed substantial self other discrepancies in medical decision making and did not make decisions that accurately reflected their patients' preferences. Finally, patients were not aware of these discrepancies and thought that the decisions their doctors made for themselves would be similar to the decisions they made for their patients. We explain these results in light of 2 current theories of self-other discrepancies in judgment and decision making: the risk-as-feelings hypothesis and the cognitive hypothesis. Our results have important implications for research on expert decision making and for medical practice, and shed some light on the process underlying self-other discrepancies in decision making. PMID- 22039767 TI - Reducing probabilistic weather forecasts to the worst-case scenario: anchoring effects. AB - Many weather forecast providers believe that forecast uncertainty in the form of the worst-case scenario would be useful for general public end users. We tested this suggestion in 4 studies using realistic weather-related decision tasks involving high winds and low temperatures. College undergraduates, given the statistical equivalent of the worst-case scenario (1 boundary of the 80% predictive interval), demonstrated biased understanding of future weather conditions compared with those given both bounds or no uncertainty information. We argue that this was due to an anchoring effect on numeric estimates, which were closer to the worst-case scenario than was warranted and increased linearly as the anchor became more extreme. In many situations tested here, anchoring in numeric estimates also extended to subsequent binary decisions, leading participants with the worst-case scenario to take action more often than did other participants. These results suggest that worst-case scenario forecasts can mislead the user. They appear to convince people that wind speeds will be higher and temperatures will be lower than what are indicated by the forecast. In addition, participants systematically "corrected" the forecast they were given. This effect was most prominent in the condition in which no uncertainty was provided, suggesting that people feel compelled to take uncertainty into account, even when it is not acknowledged by the forecast. Both the anchoring and correction biases were least evident when both bounds were provided, suggesting that balanced uncertainty leads to the best understanding of future weather conditions. PMID- 22039768 TI - Chromosome studies in cattle with hereditary zinc deficiency (lethal trait A 46). AB - Summary Blood lymphocyte and skin fibroblast cultures from cattle with hereditary zinc deficiency (lethal trait A 46) have not revealed unusually large numbers of cells with chromosomal aberrations as reported by Herzog and Hohn (6). PMID- 22039769 TI - An investigation of the pathology of Mycoplasma mastitis in the cow. AB - Summary A field case of mastitis in cows, caused by Mycoplasma agalactiae var. bovis, formed the occasion to conduct an infection experiment. Five lactating heifers were infected in the udder at different times. The cows were slaughtered 2, 5, 7, 9 and 12 days p. i. and the pathological changes were studied. The investigation indicated that the pathological picture differed with time: in the acute stage, the inflammation was characterized by exudation of mostly eosinophils in the alveoli; later on, the mastitis was identified by an interstitial reaction with eosinophils and mononuclear cells, including plasma cells and lymphocytes; in the chronic stage, progressive fibroplasia around ductuli and alveoli, with hypertrophy of alveolar epithelium, was characteristic. The pathological findings are discussed. PMID- 22039770 TI - Severe extrapyramidal syndrome in a dog caused by a Haloperidol (Serenase(r)) intoxication. AB - Summary The case history of a one-year-old male mongrel dog intoxicated with 120 mg haloperidol is described. The dog showed a coma with a severe extrapyramidal syndrome and was treated with orphenadrine. Symptoms, occurrence, and therapy of the extrapyramidal syndrome are discussed. Emphasis is laid on the importance to differentiate this syndrome from epilepsy and other neurological disorders. PMID- 22039771 TI - Diagnosis of infectious bovine rhinotracheitis by direct immunofluorescence. AB - Summary Clinical signs, virus excretion and immunofluorescence in nasal smears were studied in nine susceptible steers during a two week period, following intranasal expo-sure with IBR-virus. All animals responded with fever (ay. 3.9 days) and nasal discharge. IBR-virus was isolated from nasal swabs from 1 to 11 days after exposure (ay. 10 days), whereas fluorescence in nasal smears was observed from the second till the seventh day after infection (ay. 5.5 days). Fluorescence was most distinct 3 to 5 days after infection, which coincided with the period of fever and a serous nasal discharge. Smears from animals with a mucopurulent or slightly haemorrhagic nasal discharge were nearly always negative. For a reliable diagnosis on live animals by immunofluorescence, it is necessary to take nasal smears from several healthy looking animals with fever and a slight, preferably serous discharge. Air dried smears should be fixed in acetone within 24 hours. Seven yearlings were autopsied 3 to 11 days after intranasal exposure and subjected to a detailed investigation by the cryostat immunofluorescence technique (IFT). The tonsils of all animals were positive, followed in declining frequency by the larynx, namharynx, nasal mucosa, and pharyngeal mucosa. Besides the organs already mentioned, fluorescence was often observed in the lungs and tracheal mucosa of animals that had suffered a fatal infection of IBR in the field. The tonsils should be regarded as the organ of choice. Fluorescent foci were localized in the epithelial lining of the tonsillar crypts and in the surface epithelium of the mucosae. The direct IFT on nasal smears of suspected animals and on cryostat sections of tissues collected at autopsy offers veterinary laboratories with no facilities for tissue culture a possibility of a rapid and reliable diagnosis of IBR infections. PMID- 22039772 TI - Induction of parturition in the sow with a prostaglandin analogue (I.C.I. 80996). AB - Summary Parturition was induced in 112 gilts and sows on day 111, 112, and 113 of gestation by means of a single intramuscular injection of 175 mcg of a prostaglandin F2alpha analogue (Cloprostenol, I.C.I. 80996). No side effects were detected immediately after injection and the course of the induced parturition was normal. The interval between injection and parturition was approximately 28 hours. Induction of parturition on day 113 resulted in a significant shortening of this interval as compared with day 111 and 112. The average weights of the piglets at birth and at 5 weeks were within the normal range. The percentage of stillbirths and the loss of piglets up to weaning did not differ significantly between control and experimental groups. The practical applications of induction of parturition are discussed. PMID- 22039773 TI - Nutritional and metabolic aspects of fatty liver disease in poultry. AB - Summary There are two metabolic disorders of major commercial importance in poultry that involve the occurrence of fatty deposits in the liver. Fatty Liver and Kidney Syndrome (FLKS) affects young birds and the main manifestations, lipid infiltrations into liver and many other organs, are apparently secondary effects of the primary lesion that lies in carbohydrate metabolism. Although several nutritional and environmental factors influence FLKS, the main factor is the vitamin, biotin. In the absence of an adequate supply of biotin, the hepatic activity of pyruvate carboxylase, a biotin-dependent enzyme, becomes so low that gluconeogenesis in the liver via pyruvate becomes negligible. When the bird is then subject to a mild stress and 1or short term fasting, liver glycogen reserves become rapidly depleted and a progressive hypoglycaemia develops that ultimately proves fatal. Supplementing diets with adequate amounts of biotin can prevent the syndrome. Fatty Liver Haemorrhagic Syndrome (FLHS) is brought about by an excessive accumulation of fat in the livers of adult hens which weakens the cellular structure of the liver and allows fatal haemorrhaging to occur. The aetiology of the syndrome is not clear, but a major factor is an excessive intake of dietary energy. However, Me involvement of hormonal and toxicological factors, as well as other nutritional factors, is also possible. PMID- 22039774 TI - Haemadsorption inhibition test for the identification of Mycoplasma gallisepticum and Mycoplasma synoviae. AB - Summary Colonies of the avian mycoplasma strains Mycoplasma gallisepticum S6 and Mycoplasma synoviae WVU 1853 and two Mycoplasma synoviae isolates from this laboratory were shown to be haemadsorption positive for chicken erythrocytes. Three Mycoplasma synoviae isolates from this laboratory proved to be haemadsorption and haemagglutination negative. The haemadsorption of the mycoplasma colonies mentioned above was inhibited with specific antisera of either high or low titre. No cross-inhibition was observed. It is suggested that this test could be used for a quick tentative identification of the two avian mycoplasmas on primary solid-medium cultures. PMID- 22039775 TI - Common diseases of pet animals in West Africa. AB - Summary A brief review of the major disease of exotic pet animals in West Africa is presented, based on experience, mainly in Nigeria, with pet animals imported from Europe. The conditions mentioned are: ticks and tickborne diseases, rabies, distemper, feline panleukopenia, trypanosomiasis, hookworm and tumbu-fly infections. The control measures before departure are emphasized. PMID- 22039776 TI - Report 1977-1978 concerning Trichinella spiralis studies in the Netherlands. PMID- 22039778 TI - How the stereochemistry of a central cyclopentyl ring influences the self assembling properties of archaeal lipid analogues: synthesis and cryoTEM observations. AB - The relative stereochemistry (cis or trans) of a 1,3-disubstituted cyclopentane unit placed in the middle of tetraether archaeal bipolar lipid analogues was found to have a dramatic influence on their supramolecular self-assembling properties. The synthesis of two diastereomers varying only by the stereochemistry of the cyclopentyl unit was achieved following a multistep diastereoselective route. The corresponding lipid films were hydrated and were observed by cryoTEM. The micrographs showed several types of unilamellar nano objects such as lamellas or irregular vesicles for the cis-isomer, whereas the trans-isomer exhibited exclusively multilamellar vesicles with a regular spherical shape. Even if the cyclopentyl ring takes part of a long alkyl chain (32 carbon atoms), the pseudorotation of the carbocycle would influence the global conformation of the bipolar lipid and consequently would modify the orientation of the lactosyl polar headgroups. PMID- 22039779 TI - Contribution of individual histidines to prion protein copper binding. AB - The prion protein is well-established as a copper binding protein. The N-terminus of the protein contains an octameric repeat region with each of the four repeats containing a histidine. The N-terminus has two additional histidines distal to the repeat region that has been commonly known as the fifth site. While binding of copper by the protein has been extensively studied, the contribution of each histidine to copper binding in the full-length protein has not. Here we used a battery of mutants of the recombinant mouse prion protein to assess copper binding with both isothermal titration calorimetry and cyclic voltammetry. The findings indicate that there is extensive cooperativity between different binding sites in the protein. The two highest-affinity binding events occur at the fifth site and at the octameric repeat region. However, the first binding is that to the octameric repeat region. Subsequent binding events after the two initial binding events have lower affinities within the octameric repeat region. PMID- 22039780 TI - The ACTwatch project: methods to describe anti-malarial markets in seven countries. AB - BACKGROUND: Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti malarial drug policy decision-making. METHODS: The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012.ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. DISCUSSION: The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate findings widely for decision-making. CONCLUSIONS: ACTwatch is a unique multi-country research project that threads together anti-malarial supply and consumer behaviour to provide an evidence base to policy makers that can help determine where interventions may positively impact access to and use of quality assured ACT and RDTs. Because of its ability to detect change over time, it is well suited to monitor the effects of policy or intervention developments in a country. PMID- 22039781 TI - Gone with the plate: the opening of the Western Mediterranean basin drove the diversification of ground-dweller spiders. AB - BACKGROUND: The major islands of the Western Mediterranean--Corsica, Sardinia, and the Balearic Islands--are continental terrenes that drifted towards their present day location following a retreat from their original position on the eastern Iberian Peninsula about 30 million years ago. Several studies have taken advantage of this well-dated geological scenario to calibrate molecular rates in species for which distributions seemed to match this tectonic event. Nevertheless, the use of external calibration points has revealed that most of the present-day fauna on these islands post-dated the opening of the western Mediterranean basin. In this study, we use sequence information of the cox1, nad1, 16S, L1, and 12S mitochondrial genes and the 18S, 28S, and h3 nuclear genes, along with relaxed clock models and a combination of biogeographic and fossil external calibration points, to test alternative historical scenarios of the evolutionary history of the ground-dweller spider genus Parachtes (Dysderidae), which is endemic to the region. RESULTS: We analyse 49 specimens representing populations of most Parachtes species and close relatives. Our results reveal that both the sequence of species formation in Parachtes and the estimated divergence times match the geochronological sequence of separation of the main islands, suggesting that the diversification of the group was driven by Tertiary plate tectonics. In addition, the confirmation that Parachtes diversification matches well-dated geological events provides a model framework to infer substitution rates of molecular markers. Divergence rates estimates ranged from 3.5% My(-1) (nad1) to 0.12% My(-1) (28S), and the average divergence rate for the mitochondrial genes was 2.25% My(-1), very close to the "standard" arthropod mitochondrial rate (2.3% My(-1)). CONCLUSIONS: Our study provides the first unequivocal evidence of terrestrial endemic fauna of the major western Mediterranean islands, whose origin can be traced back to the Oligocene separation of these islands from the continent. Moreover, our study provides useful information on the divergence rate estimates of the most commonly used genes for phylogenetic inference in non-model arthropods. PMID- 22039783 TI - The chemotherapy of parasitic diseases: macrocyclic lactones. PMID- 22039782 TI - Selective, electrochemically activated biofunctionalization of In2O3 nanowires using an air-stable surface modifier. AB - Selective electrochemically activated biofunctionalization of In(2)O(3) nanowires (NWs) has been achieved, using monolayer coatings of p-dimethoxybenzene derivatives. Monolayer coatings of 4-(2,5-dimethoxyphenyl)butyl-phosphonic acid (DMP-PA) were deposited on planar indium-tin oxide (ITO) electrodes and In(2)O(3) NWs. The electrochemical behavior of the monolayer coating was first studied using ITO electrodes, as a model system for In(2)O(3) nanowires. When a potential of 950 mV vs a Ag/AgCl reference electrode is applied to an ITO electrode coated with DMP-PA in PBS buffer, the p-dimethoxyphenyl groups are converted to p benzoquinone (BQ). The electrochemically formed benzoquinone groups react readily with alkyl thiol groups via a Michael addition. The reaction strategy optimized on ITO was applied to an In(2)O(3) NW mat sample coated with DMP-PA. Applying a potential of 950 mV to metal electrodes deposited on NWs converts the DMP-PA NW coating to BQ-PA, which reacts with a thiol-terminated 20-base oligonucleotide. These NWs showed strong fluorescence response after paring with the dye labeled compliment, demonstrating that the probe was bound to the NW surface and that it remained active toward hybridization with its compliment. The unactivated DMP-PA coated NWs showed no response, demonstrating the selective electrochemical functionalization of NWs and the potential of using them in multiplex sensing. We also compared the p-dimethoxybenzene derivative to the conventional hydroquinone analog. The results show that the former can largely enhance the selectivity during the functionalization of both ITO and In(2)O(3) NWs. PMID- 22039784 TI - History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents. AB - The macrocyclic lactones enjoy a position of prominence in the control of parasites, and their history may be of interest, and even of use, in an age in which the search for chemotherapeutic agents has been transformed by modern technology. Much of their history has been recorded piecemeal in a wide variety of publications. The present review provides additional detail, and offers a personal perspective on the history of ivermectin and related avermectins. Brief notes are included on the subsequent development of other macrocyclic lactones. Milbemycin preceded the avermectins as a macrocyclic lactone of agricultural importance, but was used for a different purpose. Development of the avermectins arose from the isolation, in the laboratories of the Kitasato Institute, of a novel soil-dwelling bacterium and its transmittal (in 1974) to the laboratories of Merck & Co., Inc. There it was found (in 1975) to produce a potent anthelmintic substance, which was then identified and transmuted by interdisciplinary research into an antiparasitic product. Initially the focus was on its applicability to veterinary science and animal husbandry; and after developmental research by many scientific teams, the product was introduced commercially (in 1981) for the control of endoparasitic nematodes and ectoparasitic arthropods in livestock. Subsequently, special applications in human medicine were developed, and were successfully implemented in partnership with World Health Organization and several non-governmental organizations (NGOs). PMID- 22039785 TI - Macrocyclic lactone anthelmintics: spectrum of activity and mechanism of action. AB - Macrocyclic lactones (MLs), exemplified by the prototype of the class, ivermectin (IVM), are mainstays of programs for the control of nematode and arthropod parasites and pests. Since their introduction 30 years ago, research has revealed that they act on a family of ligand-gated chloride channels gated by glutamate, which is largely restricted to animals in the phyla Nematoda and Arthropoda. Studies on IVM in model organisms have contributed greatly to our understanding of ML pharmacology, but our understanding of the basis for differences among species and among MLs in potency and spectrum remains far from complete. PMID- 22039786 TI - Resistance to macrocyclic lactones. AB - Resistance to the macrocyclic lactones (MLs) has been confirmed or suspected in many target organisms and is a serious problem in some. For some species, such as parasitic nematodes of small ruminants, ML resistance has become severe enough to threaten effective worm control worm control. Resistance is also a major concern in horse parasites and an emerging problem in cattle. Despite this, we have insufficient understanding of the mechanisms of ML resistance, especially in nematodes. Some insect and mite agricultural pests express higher levels of detoxifying enzymes, leading to cross-resistance to other pesticide classes. A major difficulty is in the identification of true resistance and distinguishing this from other causes of treatment or prophylaxis failure--some in vitro assays for ML resistance are available but more are badly needed. Changes in the way anthelmintic drugs are used in livestock farming have been proposed, based on the treatment of those animals that would benefit most, and schemes have been devised for identifying those animals, flocks and herds. The continued sustainable use of these invaluable drugs may depend on the adoption and improvement of such schemes, as resistance is likely to become an ever more serious problem. PMID- 22039787 TI - Pharmacokinetic features of the antiparasitic macrocyclic lactones. AB - The macrocyclic lactones have pharmacokinetic properties which enhance their use against endo- and ectoparasites in animals and man. The most consistent physico chemical feature of the group which contributes to their kinetic characteristics is high lipid solubility. This appears to be necessary for their pharmacodynamic action as well as common kinetic features such as large volumes of distribution and the influence of body fat composition on their disposition. They are used in all domestic animal species and are undoubtedly influenced by the anatomical and physiological differences in these species, however body fat composition also appears to exert a major influence on distribution, metabolism and persistence between species and between breeds and individuals. A myriad of formulations have been developed to enhance the convenience of administration in the different domestic animals and the macrocyclic lactones are delivered orally, subcutaneously and topically to good effect. Lipid based excipients have been developed in "depot" formulations to extend the period of effective prevention of parasite re-infection. Subtle structural changes have been made to the macrocyclic lactone molecules to reduce distribution to the central nervous system and mammary gland, thus allowing use of some compounds such as selamectin (SLM) in "toxicity sensitive" breeds of collie dog which lack P-glycoprotein efflux systems in their central nervous systems and the use of eprinomectin (EPM) in dairy cattle with a nil-milk withdrawal period. Gender differences exist in the pharmacokinetics of these compounds which may be associated with body (fat) composition or metabolism. Feeding may also reduce the availability of macrocyclic lactones which bind particulate digestive material and parasitism may impact the kinetics of the drugs because parasitized animals have altered pathophysiological processes, especially in the gastro intestinal tract but also because of the impact which parasitism may have on the body condition (and fat deposition) in animals. The pharmacokinetics of macrocyclic lactones may be affected by coadministration with compounds which interfere with P-glycoprotein transporters and these interactions have been explored as possible mechanisms for enhancing the effectiveness of these antiparasitics. The objective of this article is to provide a comprehensive review of the pharmacokinetics of macrocyclic lactones and to interpret where that information may prove clinically useful. PMID- 22039788 TI - Macrocyclic lactones and cellular transport-related drug interactions: a perspective from in vitro assays to nematode control in the field. AB - Macrocyclic lactones (MLs) are antiparasitic drugs used against endo ectoparasites. Regarding the wide use of MLs in different species, it is likely that drug-drug interactions may occur after their co-administration with other compounds. A new paradigm was introduced in the study of the pharmacology of MLs during the last years since the interactions of MLs with ATP-binding cassete (ABC) transporters have been described. The current review article gives an update on the available information concerning drug-drug interactions involving the MLs. The basis of the methodological approaches used to evaluate transport interactions, and the impact of the pharmacology-based modulation of drug transport on the MLs disposition kinetics and clinical efficacy, are discussed in an integrated manner. A different number of in vitro and ex vivo methods have been reported to study the characterization of the interactions between MLs and ABC transporters. The production of the ABC transporters knockout mice has provided valuable in vivo tools to study this type of drug-drug interaction. In vivo trials performed in different species corroborated the effects of ABC transporter modulators on the pharmacokinetics behaviour of MLs. Important pharmacokinetic changes on plasma disposition of MLs have been observed when these compounds are co-administered with P-glycoprotein modulators. The modulation of the activity of P-glycoprotein was evaluated as a strategy not only to increase the systemic availability of MLs but also to improve their clinical efficacy. The understanding of the MLs interactions may supply relevant information to optimize their use in veterinary and human therapeutics. PMID- 22039789 TI - Extra-label use of ivermectin in some minor ruminant species: pharmacokinetic aspects. AB - The characterisation of ivermectin pharmacokinetics can be used to predict and to ensure an optimal activity in the target species and for designing programmes aimed for parasite control. Ivermectin pharmacokinetic studies performed in several minor ruminant species are reviewed in this paper with the aim of facilitating the adoption of rational basis for the establishment of appropriate dosage schedules. PMID- 22039790 TI - Recent developments in the analysis of avermectin and milbemycin residues in food safety and the environment. AB - A review of the developments on the analysis of residues of avermectins and milbemycins (both macrocyclic lactones) is presented. The macrocyclic lactones (MLs) are an important class of chemicals, which are used worldwide as veterinary drugs and as crop protection agents. As a result, residues of MLs are important from both a food safety and environmental perspective. A review of the developments in ML residues in food was carried out in detail in 2006. As a result, this paper covers recent developments in the area of food analysis, which are mainly multi-residue assays based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A brief coverage of HPLC fluorescence (HPLC-FLD) based methods is included for completeness. The paper will carry out a comprehensive review of ML residues in environmental samples. These additional sections are reflective of the growing number of research papers published on LC MS/MS and environmental applications in recent years. PMID- 22039791 TI - Toxicity in animals: target species. AB - The macrocyclic lactone endectocides typified by ivermectin are safe and effective drugs when used according to label directions. However, off-label use, misuse and overdosing can result in toxicity in animal patients as revealed by pharmacovigilance activities. Preclinical toxicity studies demonstrates that the major clinical signs of toxicity are those associated with neurotoxic effects and these are the most common adverse drug reactions noted in overdosed treated animals. Subpopulations of some strains or breeds of some species appear to be uniquely sensitive to the neurotoxic effects of the macrocyclic lactones due to enhanced brain penetration by these drugs as a result of a deficiency in P glycoprotein arising as a result of a mutation in the MDR1 gene. PMID- 22039793 TI - Ivermectin residue depletion in food producing species and its presence in animal foodstuffs with a view to human safety. AB - From a human safety perspective, the administration of ivermectin to food producing animal species entails potential risks related to the presence of drug residues in edible tissues, milk, and other derived products. The European Medicines Agency has established the maximum residue limits for ivermectin in the European Union, with values of 100 MUg.kg(-1) in fat and liver and 30 MUg.kg(-1) in kidney for all mammalian food producing species, in order to ensure that the amount of ivermectin that can be found in animal foodstuff is below dangerous levels for the consumers. According to these values, withdrawal periods after subcutaneous injection were recently established in the European Union (2009), in 49 days for products containing ivermectin as a single active substance or in combination with closantel, and in 66 days when combined with clorsulon. The marker residue for ivermectin was found to be H(2)B(1a), which is the major component of the parent compound. The tissue distribution of residues and the overall ratios of marker to total residues were generally similar in most species, and the highest concentrations of ivermectin residues were found in fat and liver with high levels also detected in injection site muscles. Ivermectin is not licensed for use in animals from which milk is produced for human consumption, however its extra-label use should be considered regarding human safety, due to its long persistence in milk and milk-derived products. PMID- 22039792 TI - Treatment of MDR1 mutant dogs with macrocyclic lactones. AB - P-glycoprotein, encoded by the multidrug resistance gene MDR1, is an ATP-driven drug efflux pump which is highly expressed at the blood-brain barrier of vertebrates. Drug efflux of macrocyclic lactones by P-glycoprotein is highly relevant for the therapeutic safety of macrocyclic lactones, as thereby GABA gated chloride channels, which are confined to the central nervous system in vertebrates, are protected from high drug concentrations that otherwise would induce neurological toxicity. A 4-bp deletion mutation exists in the MDR1 gene of many dog breeds such as the Collie and the Australian Shepherd, which results in the expression of a non-functional P-glycoprotein and is associated with multiple drug sensitivity. Accordingly, dogs with homozygous MDR1 mutation are in general prone to neurotoxicity by macrocyclic lactones due to their increased brain penetration. Nevertheless, treatment of these dogs with macrocyclic lactones does not inevitably result in neurological symptoms, since, the safety of treatment highly depends on the treatment indication, dosage, route of application, and the individual compound used as outlined in this review. Whereas all available macrocyclic lactones can safely be administered to MDR1 mutant dogs at doses usually used for heartworm prevention, these dogs will experience neurological toxicity following a high dose regimen which is common for mange treatment in dogs. Here, we review and discuss the neurotoxicological potential of different macrocyclic lactones as well as their treatment options in MDR1 mutant dogs. PMID- 22039794 TI - Acute human toxicity of macrocyclic lactones. AB - Macrocyclic lactones, including avermectins and milbemycins, are novel parasiticides and insecticides that are produced through fermentation by soil dwelling microorganisms. Although various macrocyclic lactones may differ in their potency and safety, all of them are believed to share common pharmacologic/toxicologic mechanisms, i.e. leading to paralysis and death of parasites and other target organisms via the activation of a glutamate-gated chloride channel in the invertebrate nerve and muscle cells and/or through the effect on gamma-aminobutyric acid (GABA) receptors. Ivermectin is the first macrocyclic lactone that was released for use in both animals and humans, and has demonstrated both excellent efficacy and high tolerability in the treatment of parasite infestations. Other macrocyclic lactones, such as abamectin, emamectin, and moxidectin were subsequently commercialized and have been used as insecticides and acaricides for crop protection or parasiticides for animal health. Although ivermectin therapy is generally well tolerated, adverse effects that are usually transient and mild-to-moderate can occur. Severe adverse effects are rare and can generally be effectively controlled by symptomatic measures. Non therapeutic exposures to ivermectin and other macrocyclic lactones may also result in toxic effects; significant toxicity however probably develops only after large amount of oral ingestion. Although the exact mechanisms remain unclear, macrocyclic lactones in large doses may pass through the blood-brain barrier (BBB) to produce GABA-mimetic toxic effects. Severely poisoned patients usually present with coma, hypotension, respiratory failure, and even death. Despite the lack of specific therapy, the prognosis is likely to be favorable unless the poisoned patients are complicated with severe hypotension or respiratory failure. PMID- 22039796 TI - Use of macrocyclic lactones in cattle in the USA. AB - The use of macrocyclic lactones has become the main stay for the treatment of endo- and ectoparasites in the cattle industry. Here we review those drugs that are currently approved for use in cattle in the United States. The general efficacy, tissue distribution and toxicity of each drug formulation are discussed. Included is a discussion regarding the current status for nematode anthelmintic resistance in cattle populations within the United States. Also provided is a current summary of ecological effects of macrocyclic lactones residues in manure. PMID- 22039797 TI - Macrocyclic lactones for parasite control in equids. AB - Macrocyclic lactones (MLs) revolutionized parasite control in horses and other animals. They are unique in that they are effective against arthropods and nematodes. The first of the widely used avermectins was ivermectin. In 1983, it was marketed for use in horses as an injectable formulation but was withdrawn in 1984 after about a year and half on the market because of adverse problems. It was replaced by a paste formulation and an oral/stomach tube liquid formulation. Ivermectin is highly active on bots, ascarids, large and small strongyles, pinworms, strongyloides, stomach worms, and some other internal parasite species. Another ML, moxidectin, became available in 1997 as a gel formulation for oral administration. The parasiticidal activity of this compound is similar to ivermectin except efficacy is less on the common bot (Gastrophilus intestinalis) but high on encysted small strongyles. Recently however lower than initial activity on ascarids and small strongyles has been found for both ivermectin and moxidectin. PMID- 22039795 TI - A review on the toxicity and non-target effects of macrocyclic lactones in terrestrial and aquatic environments. AB - The avermectins, milbemycins and spinosyns are collectively referred to as macrocyclic lactones (MLs) which comprise several classes of chemicals derived from cultures of soil micro-organisms. These compounds are extensively and increasingly used in veterinary medicine and agriculture. Due to their potential effects on non-target organisms, large amounts of information on their impact in the environment has been compiled in recent years, mainly caused by legal requirements related to their marketing authorization or registration. The main objective of this paper is to critically review the present knowledge about the acute and chronic ecotoxicological effects of MLs on organisms, mainly invertebrates, in the terrestrial and aquatic environment. Detailed information is presented on the mode-of-action as well as the ecotoxicity of the most important compounds representing the three groups of MLs. This information, based on more than 360 references, is mainly provided in nine tables, presenting the effects of abamectin, ivermectin, eprinomectin, doramectin, emamectin, moxidectin, and spinosad on individual species of terrestrial and aquatic invertebrates as well as plants and algae. Since dung dwelling organisms are particularly important non-targets, as they are exposed via dung from treated animals over their whole life-cycle, the information on the effects of MLs on dung communities is compiled in an additional table. The results of this review clearly demonstrate that regarding environmental impacts many macrocyclic lactones are substances of high concern particularly with larval instars of invertebrates. Recent studies have also shown that susceptibility varies with life cycle stage and impacts can be mitigated by using MLs when these stages are not present. However information on the environmental impact of the MLs is scattered across a wide range of specialised scientific journals with research focusing mainly on ivermectin and to a lesser extent on abamectin doramectin and moxidectin. By comparison, information on compounds such as eprinomectin, emamectin and selamectin is still relatively scarce. PMID- 22039798 TI - Macrocyclic lactones in the treatment and control of parasitism in small companion animals. AB - Macrocyclic lactones (MLs) have many anti-parasitic applications in small companion animal medicine. They were first developed as chemoprophylactics against heartworm (Dirofilaria immitis) infection to be applied monthly for retroactive killing of third- and fourth-stage larvae. ML-containing products formulated for oral (ivermectin, milbemycin oxime), topical (selamectin, moxidectin) or injectable sustained release (moxidectin, ivermectin) are approved for heartworm prevention in dogs or cats. Clearance of microfilariae and gradual or "soft" killing of adult heartworms constitute increasingly prevalent extra label uses of MLs against D. immitis. Some commercial ML formulations contain sufficient levels of active ingredient (milbemycin oxime, selamectin, moxidectin) to support additional label claims against gastrointestinal nematode parasites such as hookworms (Ancylostoma spp.) and ascarid round worms (Toxocara spp. and Toxascaris leonina). Beyond these approved applications, safe, extra-label uses of MLs against nematodes parasitizing the urinary tract, such as Capillaria spp., and parasites of the tissues, such as Dipetalonema reconditum, Dirofilaria repens, Thelazia spp. and Spirocerca lupi, in dogs and cats as well as exotic pets have been reported. MLs as a group have intrinsic insecticidal and acaricidal activity, and topical or otic formulations of certain compounds (selamectin, moxidectin, milbemycin oxime or ivermectin) are approved for treatment and control of fleas, certain ixodid ticks, sarcoptiform and demodectic mange mites and psoroptiform ear mites. Extra-label applications of MLs against ectoparasites include notoedric mange mites, dermanyssids such as Ornythonussus bacoti, numerous species of fur mite (e.g. Cheyletiella spp. and Lynxacarus) and trombiculids ("chiggers") in cats, dogs and nontraditional or exotic pets. PMID- 22039799 TI - Avermectin use in aquaculture. AB - The main indication for use of avermectins in aquaculture-produced fish is infestations with ectoparasitic copepods. The compounds ivermectin and emamectin benzoate are predominantly used as in-feed formulations on salmonid fish against copepods in the family Caligidae: Lepeophtheirus salmonis, Caligus elongatus and C. rogercresseyi. These agents are well-documented as very effective on all developmental stages of the parasites. The duration of effect can be up to 10 weeks. The safety margin for ivermectin is narrow, but better for emamectin benzoate. Environmental impact from these chemicals on bottom-dwelling and sediment-dwelling organisms occurs, but these are restricted to the immediate area around the production site. Avermectins are incompletely absorbed from the intestine of the fish and slowly excreted. They penetrate the blood-brain barrier of the fish, ivermectin more than emamectin benzoate. Resistance has developed against these agents in L. salmonis in almost all major salmon producing areas. The situation must be viewed as serious and can render these agents completely ineffective for salmon lice control. PMID- 22039800 TI - Ivermectin in human medicine, an overview of the current status of its clinical applications. AB - Ivermectin is a broad spectrum antiparasitic veterinary drug introduced in human medicine in 1987. It is considered the drug of choice in onchocerciasis and strongyloidiasis infections, and remains as a therapeutic option for mass treatment in lymphatic filariasis, for which it has widely proved its efficacy. While research continued for human use, new therapeutic targets for ivermectin have emerged. It is currently the better therapeutic option in the treatment of gnathostomiasis and crusted scabies, and could be an alternative option in ascariasis and Mansonella infections. Although these uses are already included in clinical guidelines, more trials are needed to increase their grade of evidence and to obtain their official approval. Concerning other minor uses such as the treatment of enterobiasis or against Trichuris trichiura, more research is still needed in order to test the real activity of ivermectin. The use of ivermectin in human medicine has shown an outstanding low rate of adverse reactions, with the exception of treatment of loiasis and onchocerciasis, where the death of a high microfilarial load may cause severe encephalopathy. However special attention must be paid to the emergence of the first documented cases of resistance in treatment of scabies. PMID- 22039801 TI - Beyond providing drugs: the Mectizan(r) donation stimulates new strategies in service delivery and in strengthening health systems. AB - The donation of Mectizan(r) by Merck & Co Inc. in 1987 "as much as was needed for as long as was needed for onchocerciasis control" was a major change from traditional corporate drug donations. The company realised that those who needed the drug most would never be able to purchase it, and so gave it away. The donation enabled the Onchocerciasis Control Programme in West Africa to add Mectizan distribution to its ongoing control strategy. For the first time there was hope for those living in other areas of Africa, Latin America and Yemen. Governments and non-governmental development organizations quickly got together to begin treatment in these new areas. Two new programmes and partnerships were created; the African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas. These programmes have been in the forefront of developing new strategies, including the Community Directed approach, which has now expanded into other disease control programmes at the community level, such as Vitamin A distribution and malaria control. This donation has led not only to the probability of elimination of onchocerciasis in the Americas in the near future, but is stimulating approaches to the elimination in Africa, in areas considered impossible five years ago. Other major pharmaceutical donations have followed, initiating the plan to eliminate lymphatic filariasis worldwide, and also stimulating interest in controlling other "neglected tropical diseases," which affect the poorest billion of the world's population, making this now a reality. PMID- 22039802 TI - Editorial: Current optical procedures used in cell biology. PMID- 22039803 TI - Image analysis of colocalization of nuclear DNA and GFP labelled HIF-1alpha in stable transformants. AB - HIF-1alpha is regarded as a target for drug development in several diseases such as cancer. For high throughput screening of HIF-1alpha-targeted drug, we need to examine the activity quantitatively. In the present study, we proposed a method where stable expression system of HIF-1alpha was combined with image correlation analysis. When the stable transformants were labeled with DRAQ5, we could detect Co2+-induced nuclear translocation by the use of cross-correlation analysis of the dual labeling images. In the case of high throughput screening for HIF-1alpha targeted drug, we should use Pearson's correlation coefficient to judge nuclear translocation. PMID- 22039804 TI - The reaction mechanism of calcium-activated photoprotein bioluminescence. AB - Calcium-activated photoproteins are important and useful bioluminescent reagents for detecting the calcium ion (Ca2+) in biological systems. In conjunction with photon imaging technology, they can be used to observe Ca2+-related life processes in a living cell. To develop useful applications of calcium-activated photoproteins, we need to understand the molecular basis of the bioluminescence reaction. For this purpose, this review describes the oxygenation, chemiexcitation, and light emission processes of calcium-activated photoproteins in the bioluminescence reaction together with the fundamental chemistry of the luminous substrate, coelenterazine, based on recent results from mechanistic chemical studies of these primary processes. Finally, the whole reaction mechanism, including the active site structures of apoproteins, along with available information about the molecular mechanism and the crystallographic structures of calcium-activated photoproteins are summarized. PMID- 22039805 TI - Low-coherence dynamic light scattering and its potential for measuring cell dynamics. AB - Fluorescence correlation spectroscopy is a powerful technique for studying the structures and dynamics of living cells. Dynamic light scattering (DLS) is also used to study dynamic characteristics and it has the potential to measure cell dynamics. However, it is difficult to apply DLS to highly scattering media. In this article, we review low-coherence dynamic light scattering (LC-DLS). It strongly suppresses the influence of multiple scattering and has a greater potential for measuring cell dynamics than conventional DLS. The properties of LC DLS are described theoretically and experimentally. Measurement of the diffusion coefficients of macromolecules in turbid media and interparticle and molecular interactions by LC-DLS is demonstrated. PMID- 22039806 TI - A novel molecular design strategy for efficient two-photon absorption materials. AB - This paper describes a novel molecular design strategy for obtaining efficient two-photon absorption (TPA) materials. The most popular strategy for enhancing the TPA cross-section (sigma(2)) of a molecule is to enhance its transition dipole moment. However, this strategy also red shifts the one-photon absorption (OPA) band. Consequently, molecules with large transition dipole moments typically exhibit strong OPA at visible wavelengths, making it difficult to use such molecules for TPA-related applications in the visible wavelength region. Therefore, an alternative molecular design principle for TPA materials to enhance the transition dipole moment is strongly required. The present paper describes a novel molecular design strategy for reducing the detuning energy by incorporating an azulenyl moiety in a large, planar pi- electron system. This strategy enhances sigma(2) without significantly red shifting the OPA band. PMID- 22039807 TI - Magnetically-modulated atomic force microscopy for analysis of soft matter systems. AB - Experimental method of studying viscoelasticity, a common idea to understand properties of microscopic biological soft matter systems, especially single biopolymer chains, using atomic force microscopy (AFM) with magnetically- driven cantilever is surveyed. The experimental setup of applying well-characterized excitation to the cantilever and the analysis method to derive the viscoelasticity of the system under study are briefly introduced. Examples of measuring viscoelasticity of single peptide molecule and single titin molecule are shown. Considering the close relation of viscoelasticity and the time-scale for nonequilibrium dynamics in soft matter, extension of the method to a frequency-resolved analysis is attempted. A result of measuring viscoelasticity spectrum of a single dextran chain is shown. Challenges in further progress of the method are also described. PMID- 22039808 TI - Single molecular observation of DNA and DNA complexes by atomic force microscopy. AB - Atomic force microscopy (AFM) provides a novel way to understand the structure function relationship of protein synthesis at a single-molecular level. High resolution AFM imaging in air, liquid and vacuum allows for single DNA, RNA and proteins to be observed at the nano-scale in addition to their conformational transitions, bound states, temporal behavior, and assembly. The recent development of frequency modulation mode AFM has led to imaging hydration structures of DNA in water and molecular polarization of DNA complexes in vacuum. Real-time imaging in near-physiological environments captures transcriptional activation with characteristic conformation of DNA-protein complexes. We review current achievements and the future potential of methodological and biological AFM to reveal insights into DNA, RNA and their complexes. PMID- 22039809 TI - Effect of isoproterenol on local contractile behaviors of rat cardiomyocytes measured by atomic force microscopy. AB - Inotropic agents induce changes in the contraction amplitude and frequency of cardiomyocytes (CMs). However, it is unknown how local contractions of CMs treated by inotropic agents behave spatiotemporally. In this study, the effect of isoproterenol, a positive inotropic agent, on local contractions of isolated neonatal rat CMs was explored by atomic force microscopy (AFM). We observed that changes in local contraction amplitude of CM in the presence of isoproterenol were heterogeneous; they were unchanged or increased, at different positions, with respect to the amplitude of untreated CMs. Interestingly, spatial heterogeneities of local contraction amplitude of CM in the presence of isoproterenol did not obviously correlate with the local elasticity, indicating that the local contractions were facilitated by cooperative dynamics of the cytoskeletal structure in relatively large regions, rather than those just under AFM indentation. Moreover, local contraction amplitude of CM in the presence of isoproterenol was not proportional to that in the control condition, showing that the former change was no longer additive in local scales. PMID- 22039810 TI - Current research on protein-protein interactions among auxin-signaling factors in regulation of plant growth and development. AB - In many signaling pathways, various factors have been isolated by molecular genetic studies and wholegenome analysis. Understanding the interactions among these factors is crucial to understanding the signaling process as a whole. Recent studies on auxin signaling in the regulation of plant growth and development have discovered primary factors interacting with each other, and elucidated a very simple pathway modulating gene expression in response to auxin. However, these studies of auxin-signaling led to the question of how such a simple pathway generates multiple types of regulation in various processes of different cells throughout the life of a plant. Here, we provide an overview of recent progress in auxin biology focusing on protein-protein interactions in the signal transduction pathway and discuss various possibilities and approaches to resolve the issue. PMID- 22039811 TI - Use of carbohydrate-conjugated nanoparticles for an integrated approach to functional imaging of glycans and understanding of their molecular mechanisms. AB - Functional analysis of carbohydrates is needed to understand the initial interface between membranes and the outer world. For this analysis we need individual protocols such as a method to modify the surfaces of nanoparticles with a variety of carbohydrates effectively and exhaustively, to synthesize an oligosaccharide on each particle's surface by chemical or enzymatic sugar elongation reaction, and to analyze the binding properties of carbohydrates. In this article, we describe the basic strategies for scooping up proteins from crude sample mixtures via interaction with carbohydrates. This approach was used to identify proteins that interacted with GM2, a ganglioside that is abundant on the surfaces of human lung cancer cells. PMID- 22039812 TI - Direct quantification of mitochondria and mitochondrial DNA dynamics. AB - Mitochondria are known to be one of major organelles within a cell and to play a crucial role in many cellular functions. These organelles show the dynamic behaviors such as fusion, fission and the movement along cytoskeletal tracks. Besides mitochondria, mitochondrial DNA is also highly motile. Molecular analysis revealed that several proteins are involved in mitochondria and mitochondrial DNA dynamics. In addition to the degeneration of specific nerves with high energy requirement, mutation of genes coding these proteins results in metabolic diseases. During the last few years, a significant amount of relevant data has been obtained on molecular basis of these diseases but mitochondrial dynamics in cells derived from the patients is poorly understood. So far time-lapse fluorescence microscopy, fluorescence recovery after photo bleaching and image correlation methods have been used to study organellar motion. Especially, image correlation method has possibility to evaluate diffusion coefficient of mitochondria and mitochondrial DNA simultaneously and directly. When we search candidates for compounds that modulate mitochondrial dynamics by high throughput screening, image correlation method may be useful although the careful interpretation is required for crowded and heterogeneous environment within a cell. PMID- 22039813 TI - Atomic force microscopy for the examination of single cell rheology. AB - Rheological properties of living cells play important roles in regulating their various biological functions. Therefore, measuring cell rheology is crucial for not only elucidating the relationship between the cell mechanics and functions, but also mechanical diagnosis of single cells. Atomic force microscopy (AFM) is becoming a useful technique for single cell diagnosis because it allows us to measure the rheological properties of adherent cells at any region on the surface without any modifications. In this review, we summarize AFM techniques for examining single cell rheology in frequency and time domains. Recent applications of AFM for investigating the statistical analysis of single cell rheology in comparison to other micro-rheological techniques are reviewed, and we discuss what specificity and universality of cell rheology are extracted using AFM. PMID- 22039814 TI - Current status and future prospects for research on tyrosine sulfation. AB - Tyrosine (Tyr) sulfation is a common posttranslational modification of secreted proteins or membrane-bound proteins that is implicated in numerous physiological and pathological processes. The Tyr sulfation modifies proteinprotein interactions involved in leukocyte adhesion, homeostasis, and receptor-mediated signaling. To data, 80 Tyrsulfated proteins have been identified. As new methodologies and bioinformatics for the detection of Tyr sulfation become available, the number of Tyr-sulfated acceptor proteins discovered is bound to increase. Further, recent advances in microscopy and fluorescence technology will provide information on the true spatial and temporal nature of Tyr-sulfated proteins within the intact cell. This review summarizes the methods for the detection of Tyr O-sulfation as well as the biological functions of sulfated Tyr. Further, illustrative examples of the impact of Tyr sulfation on the pharmacological properties are presented. PMID- 22039815 TI - Synthesis and application of visible light sensitive azobenzene. AB - Methods for regulating peptide conformation by non-harmful light stimuli can be useful for remotely controlling cellular functions in vitro. Here, we synthesized a series of p-heteroatom-substituted azobenzenes and studied their photoisomerization properties. The trans-isomer of p-sulfur-substituted azobenzene was effectively isomerized by visible light irradiation and the cis isomer was thermally stable at physiological temperature. We developed a novel visible light sensitive amino acid (AZO), via p-sulfur-substituted azobenzene, and utilized it as a photosensitive modulator of the SV40 nuclear localization signal (NLS). The cellular uptake of the AZO-NLS conjugate was controlled by visible light irradiation. Our technology can be utilized for regulating not only the cellular uptake, but also the function of peptides within cells by non harmful visible light irradiation. PMID- 22039816 TI - Fluorescence imaging of mitochondria in living cells using a novel fluorene derivative with a large two-photon absorption cross-section. AB - We have examined optical properties of a fluorene derivative with two positively charged substituents, 1,1'- diethyl-4,4'-(9,9-diethyl-2,7-fluorenediyl-2,1 ethanediyl)dipyridinium perchlorate (1), in water. The photoluminescence quantum yield of 1 was relatively high (35%) for use as a fluorescent probe in water. We also examined two-photon absorption (TPA) properties of 1 in methanol. The maximum value of the TPA cross-section (730 GM at 750 nm, 1 GM = 10(-50) cm4 s photon-1 molecule-1) was larger than that for most two-photon-excited fluorescent dyes including a classical mitochondria-selective fluorescent dye rhodamine 123. Preliminary fluorescence imaging experiments of the mitochondria in living Paramecium caudatum and HeLa cells were carried out with 1. Bright green fluorescence was observed from the mitochondria in both living cells loaded 1 without toxicity effects. These our results indicate that water-soluble fluorene derivative 1 is a promising candidate as a two-photon-excited fluorescence probe for mitochondria in living cells. PMID- 22039817 TI - Highly controllable optical tweezers using dynamic electronic holograms. AB - Dielectric particles including living cells are trapped within focused laser beam spots, and as a result, they can be transferred by displacing the beam spots. Such the particle manipulating technique is called optical tweezers. Holographic optical tweezers (HOT) enables highly flexible and precise control of particles, introducing holography technique to them. HOT is one of the most expected techniques for investigations of cell-cell signaling which require precise arraying of living cells. We had developed a new highly controllable HOT system where two different intensity patterns, a carrier beam spot and a beam array, are generated quasi-simultaneously by time-division multiplexing. Particles are transferred to the beam array by the carrier beam spot displaced in real time by phase shifting of holograms. In this review, we introduce our work, the construction of the system, demonstration of manipulating particles and investigations of the spatio- temporal stability of trapped particles in our system. PMID- 22039818 TI - Recent advances in the study of glycosphingolipids. AB - Glycosphingolipids (GSLs) are present in all mammalian cell plasma membranes and intracellular membrane structures. They are especially concentrated in plasma membrane lipid domains that are specialized for cell signaling. Plasma membranes show typical structures called rafts and caveola domain structures, with large amounts of sphingolipids, cholesterol, and sphingomyelin in the cell membranes. Plasma membranes have two faces, many kinds of receptors for intercellular signal transducers such as GPI-anchored proteins on the exoplasmic faces of the rafts/caveolae and src family kinases on the cytosolic face. Thus they play a role in transmembrane signal transduction, following the phosphorylation of some substrates and gene expression. On the other hand, their functions have become clear through the study of gene-manipulated mice. For further advances, a visual method to display diversity of biological functions is necessary. For this purpose, the use of high-performance microscopes and live cell imaging technologies are useful for more detailed understanding. PMID- 22039819 TI - Editorial: novel high through-put approach and molecular modelling in drug discovery from natural products and clinical implications. PMID- 22039820 TI - In silico search for drug targets of natural compounds. AB - Natural compounds represent a significant source for the development of novel medicines. Finding the target proteins for a natural compound is the most important step towards understanding its molecular mechanism for therapeutic usage. In fact, the search for target proteins could be considered the first step of the drug discovery and development pipeline. While experimental determination of compound-protein interactions remains very challenging, effective in silico approaches have been developed and have demonstrated appealing advantages, including their low-cost and capability to scale up easily. The goal of this article is to provide an introduction to in silico search for drug targets of natural compounds. I first review currently available natural compounds databases and human gene/protein databases, and the rapidly emerging databases for known drug-target interactions. These resources provide the 'materials' for in silico approaches and define the gold standard of 'positives' for evaluating them. I then introduce three classes of computational methods for target identification of natural compounds, namely molecular docking, quantitative structure-activity relationship (QSAR) modeling, and data mining and integrative analysis. Use of these methods is explained using real examples, and the advantages and disadvantages of each method are compared. As these state-of-the-art methods continue to mature amid significant challenges, this field appears poised for a period of significant growth, with untold benefits to drug discovery and natural product development. PMID- 22039821 TI - Pharmacophore, QSAR, and binding mode studies of substrates of human cytochrome P450 2D6 (CYP2D6) using molecular docking and virtual mutations and an application to chinese herbal medicine screening. AB - The highly polymorphic human cytochrome P450 2D6 (CYP2D6) metabolizes about 25% of currently used drugs. In this study, we have explored the interaction of a large number of substrates (n = 120) with wild-type and mutated CYP2D6 by molecular docking using the CDOCKER module. Before we conducted the molecular docking and virtual mutations, the pharmacophore and QSAR models of CYP2D6 substrates were developed and validated. Finally, we explored the interaction of a traditional Chinese herbal formula, Fangjifuling decoction, with CYP2D6 by virtual screening. The optimized pharmacophore model derived from 20 substrates of CYP2D6 contained two hydrophobic features and one hydrogen bond acceptor feature, giving a relevance ratio of 76% when a validation set of substrates were tested. However, our QSAR models gave poor prediction of the binding affinity of substrates. Our docking study demonstrated that 117 out of 120 substrates could be docked into the active site of CYP2D6. Forty one out of 117 substrates (35.04%) formed hydrogen bonds with various active site residues of CYP2D6 and 53 (45.30%) substrates formed a strong pi-pi interaction with Phe120 (53/54), with only carvedilol showing pi-pi interaction with Phe483. The active site residues involving hydrogen bond formation with substrates included Leu213, Lys214, Glu216, Ser217, Gln244, Asp301, Ser304, Ala305, Phe483, and Phe484. Furthermore, the CDOCKER algorithm was further applied to study the impact of mutations of 28 active site residues (mostly non-conserved) of CYP2D6 on substrate binding modes using five probe substrates including bufuralol, debrisoquine, dextromethorphan, sparteine, and tramadol. All mutations of the residues examined altered the hydrogen bond formation and/or aromatic interactions, depending on the probe used in molecular docking. Apparent changes of the binding modes have been observed with the Glu216Asp and Asp301Glu mutants. Overall, 60 compounds out of 130 from Fangjifuling decoction matched our pharmacophore model for CYP2D6 substrates. Fifty four out of these 60 compounds could be docked into the active site of CYP2D6 and 24 of 54 compounds formed hydrogen bonds with Glu216, Asp301, Ser304, and Ala305 in CYP2D6. These results have provided further insights into the factors that determining the binding modes of substrates to CYP2D6. Screening of high-affinity ligands for CYP2D6 from herbal formula using computational models is a useful approach to identify potential herb-drug interactions. PMID- 22039822 TI - Integrated analysis on the physicochemical properties of dihydropyridine calcium channel blockers in grapefruit juice interactions. AB - Concomitant consumption of grapefruit juice (GFJ) causes increases in the plasma concentration of a variety of drugs due to inhibition of intestinal CYP3A enzyme. Dihydropyridine calcium channel blockers belong to the category of drugs that are most prone to undergo such interaction. Increases in area under the plasma concentration-time curve (AUC) due to GFJ differ greatly depending on the dihydropyridine administered. Therefore, a meta-analysis of each dihydropyridine was performed based on available literature. The criteria for using a publication were: subjects were healthy adults, dihydropyridines were taken with GFJ concomitantly or within one hour after intake of the juice, and the control group administered water in place of GFJ. In these studies, the investigations on GFJ interactions with 13 dihydropyridines such as amlodipine, azelnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine and pranidipine were reported. As a result of meta-analyses, statistically significant interactions were not identified in amlodipine. Next, correlation analyses between the physicochemical properties and interaction strengths of the dihydropyridines were performed to clarify the cause of the variation in the strengths that was dependent on the dihydropyridine. LogP, molecular weight, topological polar surface area (tPSA), molar refractivity, water diffusion, molecular volume, molecular density, molecular polarizability, and refractive index were calculated from the chemical structures. The interaction strength was defined as the logarithmic values of the increasing AUC ratio. The correlation analyses indicated a relationship of logP and tPSA with the interaction strengths. These findings suggest that the wide difference in the potency of interaction of each dihydropyridine may be explained by the presence of hydrophobic and electrostatic interactions between dihydropyridines and intestinal CYP3A enzyme. PMID- 22039823 TI - Herb-drug interactions: methods to identify potential influence of genetic variations in genes encoding drug metabolizing enzymes and drug transporters. AB - Herbal supplements are often used concomitantly with conventional medications resulting in considerable potential for herb-drug interactions. These interactions, which are generally through interfering with pharmacokinetic and/or pharmacodynamic pathways, may result in beneficial effects or more often adverse reactions such as toxicity or treatment failure and may be influenced by multiple environmental and/or genetic factors. The pharmacogenetic approach may help to identify some interactions which may be more pronounced or only occur in specific groups of subjects although the complex nature of the herbal medicines may limit the discovery of such an interaction. Preclinical studies such as gene expression profiling in rodent liver may help to define metabolic pathways influenced by herbal medicines and facilitate more accurate targeting of human in vivo studies. This review discusses the mechanisms of herb-drugs interaction and the potential influence of genetic variation on herb-drug interactions based on available clinical evidence. PMID- 22039824 TI - Detection of the K99 antigen of Escherichia coli in calf faeces by enzyme-linked immunosorbent assay (ELISA). AB - Summary An enzyme-linked immunosorbent assay (ELISA) is presented for the detection of the K99 antigen of Escherichia coli in calf faeces. False-positive reactions were not observed with K99-negative strains and with several viral antigens. Only bovine coronavirus caused slight positive reactions which could be eliminated by a blocking test. As compared with the conventional procedure for the detection of the K99 antigen, ELISA seemed to be at least as sensitive and had the advantage that samples could be stored at -20 degrees C before testing. In addition many samples could be handled at the same time and the results became available quickly. By carrying out the assay as a blocking test, specific antibody against K99 in serum or colostrum could be detected and titrated. PMID- 22039825 TI - Egg drop syndrome, 1976 (EDS'76). AB - Summary A description is given of the new clinical condition in fowl now known as EDS 76. This is characterised by the production of thin shelled, soft shelled and shell less eggs by apparently healthy birds. The effects on egg production are seen around 30 weeks of age and are seen either as an apparent fall in production or as a failure to obtain predicted production targets. Haemagglutinating viruses have been isolated from these flocks and evidence from experimental and field investigations suggest these are the aetiological agents of EDS 76. Biochemical and biological studies indicate that these viruses are duck adenoviruses. Epidemiological evidence suggests the virus is egg transmitted and that lateral spread between flocks is not important if care is taken whilst bleeding and vaccinating flocks. It is postulated that this virus may have been introduced into flocks by the use of a contaminated vaccine. Control in Northern Ireland has been by eradication of the virus from the basic breeding stock. PMID- 22039826 TI - The activity of albendazole against adult and larval gastrointestinal nematodes in naturally infected calves in the Netherlands. AB - Summary The activity of albendazole against gastrointestinal helminths in naturally infected calves in the Netherlands was tested. The calves were in their fist grazing season and kept in two groups of ten. One of these groups was grazed alternately with sheep. Five out of each group were drenched with albendazole (7.5 mg/kg) on the day they were housed (November 1). Before and 2, 14, and 28 days after treatment individual faecal samples were taken from all calves and larval cultures were made. Ten calves, six treated and four untreated, were killed for post mortem studies 14 days after treatment The remaining calves were slaughtered 14 days later. The drug was highly effective in reducing the egg output, measured as the number of larvae cultured per gram of faeces. Compared with the untreated calves, the reduction was more than 99% two days after treatment, 100% at 14 days, and 99% after 28 days. It was shown that egg output 28 days after treatment came from worms which had developed from arrested larvae of Ostertagia ostertagi that had survived treatment. Post mortem results showed an efficacy of 100% against adult O. ostertagi, of almost 100% against Trichostrongylus axei, and 100% against adult and larval Cooperia oncophora. Twenty-eight days after treatment, the reduction of arrested early fourth stages of O. ostertagi was 85% in comparison with the untreated calves. Apparently less effect was found against Trichuris ovis at the given dose rate. PMID- 22039827 TI - Persistent right aortic arch associated with a persistent left ductus arteriosus and an interventricular septal defect in a horse. AB - Summary In this article a description is given of the clinical and postmortem findings of a persistent right aortic arch in association with a persistent left ductus arteriosus and a ventricular septal defect in a horse. PMID- 22039828 TI - Preliminary investigation into the usefulness of the indirect haemagglutination. AB - Summary To give an impression of the usefulness of indirect haemagglutination (IHA) in the diagnosis of lungworm infections in cattle under practical conditions, five calves vaccinated against Dictyocaulus viviparus and five unvaccinated calves were periodically subjected to clinical, parasitological, and serological examinations over a period of seven months. All calves grazed on a lungworm-infected plot. 82% of the observations in unvaccinated calves, which were positive with respect to one or more of the used parameters, concerned IHA positive animals which, however, showed negative results with the parasitic parameters. The titre variation of the serological examination was a further indication of the fact that the IHA detected antibodies against lungworm antigens. No indications of false positive reactions were obtained. An investigation carried out on 46 farms on the correlation between serological and clinical findings on lungworm infections revealed a positive correlation in 80% of the groups between results obtained with both methods. The authors consider that IHA offers good prospects for the diagnosis of lung-worm infections. PMID- 22039829 TI - Comparison of dairy cows with low or high rate of udder infection. AB - Summary Within farms, animals with low and high rate of udder infection were selected from data of a mastitis-prevention field experiment during 3.5 years. Differences between the groups in udder conformation and milkability appeared to be small but were consistently to the disadvantage of the high infection rate group. In the course of at least three preceding lactations the percentage of quarters infected at any time was 53 per cent in the low and 91 percent in the high infection rate group. The number of infections per quarter infected was 1.53 for the low infection rate group and 2.53 for the high infection rate group. As compared with infection-free quarters it was shown that the duration of infections with udder pathogens was significantly shortened if a quarter was already infected with secondary, i.e. less or non-pathogenic, bacteria. It was not possible to demonstrate differences in cell count or immunoglobulin levels in infection-free quarters between the low and high infection rate groups. PMID- 22039830 TI - Veterinary experiences as a Japanese prisoner of war and ex-POW along the Burma railroad from 1942 to January 1946. AB - Summary As a prisoner of war the writer was working for nearly three years in different POW camps, and outside them, along the Burma railway from Thanbyuyzat in southern Burma up to Kanchanabury in Thailand. In the army of the Netherlands Indian archipelago (KNIL) he had the military rank of reserve horse-doctor. In civilian life he was attached to the Veterinary Institute in Buitenzorg (now Bogor) as a veterinary bacteriologist. His task as a POW became that of meathygienist and supervisor of the living animals in the camps. In this function he diagnosed swine fever in growing pigs which had mainly been fed on the offal of the Japanese kitchen. The acute course and the pathological alterations observed during the post-mortem examinations were identical with those of the Southern-African type of the disease. In slaughter cattle the author diagnosed some cases of lung tuberculosis, one of anthrax, several of rinderpest, some of rhinal granulomatosis and one of foot and mouth disease. In chickens he found NCD (pseudo-fowlpest) and in ducklings a mortal disease which the author then called 'keeling disease' but which he many years later, recognized as virus hepatitis. As assistant bacteriologist and ex-POW he joined the British regimental hospital in Bangkok. Here he had the opportunity to assist the bacteriologist pathologist, Maj. C. R. Peck IMS / IAMC in diagnosing the first case of melioidosis in an ex POW of the KNIL who died from the sub-acute infection, notwithstanding treatment in the hospital with sulfa-drugs and penicillin. PMID- 22039832 TI - Twist does a twist to the reactivity: stoichiometric and catalytic oxidations with twisted tetramethyl-IBX. AB - The methyl groups in TetMe-IBX lower the activation energy corresponding to the rate-determining hypervalent twisting (theoretical calculations), and the steric relay between successive methyl groups twists the structure, which manifests in significant solubility in common organic solvents. Consequently, oxidations of alcohols and sulfides occur at room temperature in common organic solvents. In situ generation of the reactive TetMe-IBX from its precursor iodo-acid, i.e., 3,4,5,6-tetramethyl-2-iodobenzoic acid, in the presence of oxone as a co-oxidant facilitates the oxidation of diverse alcohols at room temperature. PMID- 22039833 TI - Heat shock protein 70 prevents both tau aggregation and the inhibitory effects of preexisting tau aggregates on fast axonal transport. AB - Aggregation and accumulation of the microtubule-associated protein tau are associated with cognitive decline and neuronal degeneration in Alzheimer's disease and other tauopathies. Thus, preventing the transition of tau from a soluble state to insoluble aggregates and/or reversing the toxicity of existing aggregates would represent a reasonable therapeutic strategy for treating these neurodegenerative diseases. Here we demonstrate that molecular chaperones of the heat shock protein 70 (Hsp70) family are potent inhibitors of tau aggregation in vitro, preventing the formation of both mature fibrils and oligomeric intermediates. Remarkably, addition of Hsp70 to a mixture of oligomeric and fibrillar tau aggregates prevents the toxic effect of these tau species on fast axonal transport, a critical process for neuronal function. When incubated with preformed tau aggregates, Hsp70 preferentially associated with oligomeric over fibrillar tau, suggesting that prefibrillar oligomeric tau aggregates play a prominent role in tau toxicity. Taken together, our data provide a novel molecular basis for the protective effect of Hsp70 in tauopathies. PMID- 22039834 TI - Parental transfer of polybrominated diphenyl ethers (PBDEs) and thyroid endocrine disruption in zebrafish. AB - Polybrominated diphenyl ethers (PBDEs) have the potential to disrupt the thyroid endocrine system. The objective of the present study was to characterize the disrupting effects of long-term exposure on the thyroid endocrine system in adult fish and their progeny following parental exposure to PBDEs. Zebrafish (Danio rerio) embryos were exposed to environmentally relevant concentrations (1, 3, and 10 MUg/L) of the PBDE mixture DE-71 for 5 months until sexual maturation. In the F0 generation, exposure to DE-71 significantly increased plasma thyroxine (T4) but not 3,5,3'-triiodothyronine (T3) in females. This increased T4 was accompanied by decreased mRNA levels of corticotropin-releasing hormone (CRH) and thyrotropin beta-subunit (TSHbeta) in the brain. The F1 generation was further examined with or without continued DE-71 treatment conditions. Exposure to DE-71 in the F0 fish caused significant increases in T4 and T3 levels in the F1 larvae and modified gene expressions in the hypothalamic-pituitary-thyroid axis (HPT axis) under both conditions. Decreased hatching and inhibition of growth in the F1 offspring were observed in the condition without DE-71 treatment. Continued DE 71 treatment in the F1 embryos/larvae resulted in further decreased hatching, and increased malformation rates compared with those without DE-71 exposure. Analysis of F1 eggs indicated that parental exposure to DE-71 could result in a transfer of PBDEs and thyroid hormones (THs) to their offspring. For the first time, we demonstrated that parental exposure to low concentrations of PBDEs could affect THs in the offspring and the transgenerational PBDE-induced toxicity in subsequent nonexposed generations. PMID- 22039835 TI - The relative effect of citral on mitotic microtubules in wheat roots and BY2 cells. AB - The plant volatile monoterpene citral is a highly active compound with suggested allelopathic traits. Seed germination and seedling development are inhibited in the presence of citral, and it disrupts microtubules in both plant and animal cells in interphase. We addressed the following additional questions: can citral interfere with cell division; what is the relative effect of citral on mitotic microtubules compared to interphase cortical microtubules; what is its effect on newly formed cell plates; and how does it affect the association of microtubules with gamma-tubulin? In wheat seedlings, citral led to inhibition of root elongation, curvature of newly formed cell walls and deformation of microtubule arrays. Citral's effect on microtubules was both dose- and time-dependent, with mitotic microtubules appearing to be more sensitive to citral than cortical microtubules. Association of gamma-tubulin with microtubules was more sensitive to citral than were the microtubules themselves. To reveal the role of disrupted mitotic microtubules in dictating aberrations in cell plates in the presence of citral, we used tobacco BY2 cells expressing GFP-Tua6. Citral disrupted mitotic microtubules, inhibited the cell cycle and increased the frequency of asymmetric cell plates in these cells. The time scale of citral's effect in BY2 cells suggested a direct influence on cell plates during their formation. Taken together, we suggest that at lower concentrations, citral interferes with cell division by disrupting mitotic microtubules and cell plates, and at higher concentrations it inhibits cell elongation by disrupting cortical microtubules. PMID- 22039836 TI - Optimization of a potent class of arylamide colony-stimulating factor-1 receptor inhibitors leading to anti-inflammatory clinical candidate 4-cyano-N-[2-(1 cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1H-imidazole 2-carboxamide (JNJ-28312141). AB - A class of potent inhibitors of colony-stimulating factor-1 receptor (CSF-1R or FMS), as exemplified by 8 and 21, was optimized to improve pharmacokinetic and pharmacodynamic properties and potential toxicological liabilities. Early stage absorption, distribution, metabolism, and excretion assays were employed to ensure the incorporation of druglike properties resulting in the selection of several compounds with good activity in a pharmacodynamic screening assay in mice. Further investigation, utilizing the type II collagen-induced arthritis model in mice, culminated in the selection of anti-inflammatory development candidate JNJ-28312141 (23, FMS IC(50) = 0.69 nM, cell assay IC(50) = 2.6 nM). Compound 23 also demonstrated efficacy in rat adjuvant and streptococcal cell wall-induced models of arthritis and has entered phase I clinical trials. PMID- 22039837 TI - Inbreeding depression in red deer calves. AB - BACKGROUND: Understanding the fitness consequences of inbreeding is of major importance for evolutionary and conservation biology. However, there are few studies using pedigree-based estimates of inbreeding or investigating the influence of environment and age variation on inbreeding depression in natural populations. Here we investigated the consequences of variation in inbreeding coefficient for three juvenile traits, birth date, birth weight and first year survival, in a wild population of red deer, considering both calf and mother's inbreeding coefficient. We also tested whether inbreeding depression varied with environmental conditions and maternal age. RESULTS: We detected non-zero inbreeding coefficients for 22% of individuals with both parents and at least one grandparent known (increasing to 42% if the dataset was restricted to those with four known grandparents). Inbreeding depression was evident for birth weight and first year survival but not for birth date: the first year survival of offspring with an inbreeding coefficient of 0.25 was reduced by 77% compared to offspring with an inbreeding coefficient of zero. However, it was independent of measures of environmental variation and maternal age. The effect of inbreeding on birth weight appeared to be driven by highly inbred individuals (F = 0.25). On the other hand first year survival showed strong inbreeding depression that was not solely driven by individuals with the highest inbreeding coefficients, corresponding to an estimate of 4.35 lethal equivalents. CONCLUSIONS: These results represent a rare demonstration of inbreeding depression using pedigree based estimates in a wild mammal population and highlight the potential strength of effects on key components of fitness. PMID- 22039838 TI - Got ACTs? Availability, price, market share and provider knowledge of anti malarial medicines in public and private sector outlets in six malaria-endemic countries. AB - BACKGROUND: Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. METHODS: Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. RESULTS: 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (< 25%). In the public/not-for-profit sector, first-line quality-assured ACT was available for free in all countries except Benin and the DRC (US$1.29 [Inter Quartile Range (IQR): $1.29-$1.29] and $0.52[IQR: $0.00-$1.29] per adult equivalent dose respectively). In the private sector, first-line quality-assured ACT was 5-24 times more expensive than non-artemisinin therapies. The exception was Madagascar where, due to national social marketing of subsidized ACT, the price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share. Most anti-malarials were distributed through the private sector, but often comprised non-artemisinin therapies, and in the DRC and Nigeria, oral artemisinin monotherapies. Provider knowledge of the first-line treatment was significantly lower in the private sector than in the public/not for-profit sector. CONCLUSIONS: These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria. PMID- 22039839 TI - Critical assessment of progress of medical sciences in Iran and Turkey: the way developing countries with limited resources should make effective contributions to the production of science. AB - BACKGROUND: Scientific progress is an important indicator for the social and economic developments of any country. According to various reports, worldwide, Iran has the most growth in the field of science due to a high increase in the numbers of publications during the past decade. The aim of this study is to assess not only the quantity, but also the quality of publications of indexed Iranian journals and compare them to Turkey, as an Islamic neighboring country, in addition to the contributions of these two countries to our knowledge. A number of international journals with high impact factors were selected to assess the contributions of scientists from Iran and Turkey to the medical sciences. METHODS: English medical journals from Iran and Turkey indexed by the ISI Web of Sciences with known impact factors (IF) announced at the beginning of 2010 were included for evaluation. We calculated the number of all articles published from the beginning of 2007 until the October 2010, the number of total citations, and citations from authors outside both countries for each journal. In addition, we selected all articles cited at least six times by authors outside of both countries and discussed their content with regard to originality and novelty, as well as their contributions to current knowledge. Furthermore, 60 international journals in basic or clinical research with IF greater than 6 were selected for the magnitude of contributions of both countries to our scientific knowledge. RESULTS: In 2010, out of a total of 21 Iranian journals indexed in ISI since 2007, only 12 have a known IF with a mean of 0.39 (range: 0.07-0.97), whereas out of 28 Turkish medical journals indexed in ISI, 15 have a known IF (mean: 0.35, range: 0.05-0.82). The total number of articles published since 2007 from Iran, total citations and total citations by authors from outside Iran were 2080, 1218, and 463, respectively. The same data related to Turkish journals were 4876, 2036, and 1331, respectively. Indeed, the mean citations per article by foreign authors for Iranian and Turkish researchers were 0.19 and 0.3, respectively. Of the total articles during this period, only seven from Iran and nine from Turkey have been cited at least six times by authors outside the two countries. Iran had 23 and Turkey 37 original publications in highly reputable international journals. Turkey was more represented in basic research and clinical observational studies than Iran. CONCLUSION: Despite high numbers of published articles, both countries have medical journals with very low comparable citation rates and IF. Only one out of three Turkish articles is cited once by authors outside of Turkey and one of five Iranian articles is cited by authors outside Iran. The few high-cited articles address new therapies and interventional studies or diseases commonly encountered regionally, and are the results of the efforts of a few individuals in highly specialized fields. Turkish scientists are inclined to publish their scientific works more than Iranians in distinguished international journals. These articles deal more with regional diseases that are not common in Western countries. Developing countries can only contribute to world science when they focus their efforts on teamwork in order to research ways to solve country specific diseases and their own health problems. PMID- 22039840 TI - Six-year follow up of imatinib therapy for newly diagnosed chronic myeloid leukemia in Iranian patients. AB - BACKGROUND: The present study reported a six-year follow up of patients with chronic myeloid leukemia who were on imatinib therapy. METHODS: We performed a retrospective study on a total of 417 patients diagnosed with chronic-phase, Philadelphia-positive (Ph+) chronic myeloid leukemia within six months before study entry. Patients were eligible for the study if they were between 18 and 70 years of age. Enrolled patients were treated at an initial dose of 400 mg of imatinib. RESULTS: The mean age of 417 patients was 40.9+/-14.5 years; 220 (52%) were men and 197 (47.2%) were women. Complete hematologic response at three months occurred in 99% of patients, 221 (53%) before four weeks and 196 (47%) after four weeks. Adverse events occurred in 17 (4.1%) of patients, relapse in 46 (11%) and death in 31 (7.4%) of our studied population. At 72 months, the estimated rate of overall survival rate was 89%. DISCUSSION: Our findings showed the efficacy and safety of imatinib mesylate among Iranian patients with chronic myeloid leukemia by hematological and molecular response. PMID- 22039841 TI - Assessment of a real-time PCR method to detect human non-cryptococcal fungal meningitis. AB - BACKGROUND: The signs and symptoms associated with fungal meningitis are similar to those seen with more common bacterial infections. In this study, we investigate whether Aspergillus or Candida DNA can be detected in cerebrospinal fluid (CSF) samples from patients suspected of fungal meningitis using real-time PCR assay. METHODS: From April 2007 to November 2009, we evaluated CSF samples and sera from patients with risk factors for cerebral fungal meningitis in Nemazi Hospital, Shiraz University of Medical Sciences, Iran, by real-time PCR assay and routine mycological studies (direct microscopy examination and culture). Two CSF and two serum samples from each patient were examined. RESULTS: CSF and serum samples from 38 patients (total: 152) suspected of fungal meningitis were examined. India ink staining and KOH smear were negative for all patients. C. albicans was isolated from two CSF samples. There were ten patients with positive real-time PCR results in their CSF samples: three patients had C. albicans, one with C. glabrata, four with Aspergillus species and two with both C. albicans and Aspergillus species DNA. Four patients had positive serum results for Aspergillus or Candida infections. CONCLUSION: Considering the findings, it seems that molecular examination can help in the diagnosis of fungal meningitis in patients with clinical and radiological presentations. Further studies should be conducted in other regions and settings to confirm these findings. PMID- 22039842 TI - Association between apolipoprotein E-polymorphism and Ischemic heart disease patients with or without type 2 diabetes mellitus: a preliminary study in Kuwait. AB - BACKGROUND: We investigated the association between apolipoprotein E polymorphism and ischemic heart disease with or without type 2 diabetes in Kuwait and examined the impact of apolipoprotein E polymorphism in diabetic patients. METHODS: The present study was conducted from January 2005 to June 2006 in the Diabetic Clinic of Al-Amiri and Al-Sabah Hospitals in Kuwait City. Apolipoprotein E polymorphism was assessed in 250 subjects of which 83 were ischemic heart disease patients (41 diabetic and 42 non-diabetic) and 105 were diabetic patients without ischemic heart disease. Results were compared with 62 healthy controls. Apolipoprotein E polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Apolipoprotein E3 allele was the most commonly occurring form. The frequency of apolipoprotein E4 was higher in ischemic heart disease patients with type 2 diabetes (39%) and the non-diabetic (31%) group, but lower in the diabetic (20%) and control groups (16%). CONCLUSION: Apolipoprotein E4 allele may be related to the development of ischemic heart disease in patients with or without type 2 diabetes in Kuwait. However, future studies with larger population sizes are needed to establish such relationship. PMID- 22039843 TI - Modulation of WIN55,212-2 state-dependent memory by alpha2-adrenergic receptors of the dorsal hippocampus. AB - BACKGROUND: An overlapping distribution of alpha2-adrenergic receptors with cannabinoid receptors has been reported in certain brain structures such as the dorsal hippocampus. Thus, functional interactions between cannabinoid and alpha2 adrenergic systems in cognitive control seem possible. In the present study, we examine the possible role of alpha2-adrenergic receptors of the dorsal hippocampus on WIN55,212-2 state-dependent learning. METHODS: Adult male Wistar rats were bilaterally implanted with chronic cannulae in the CA1 regions of their dorsal hippocampi trained in a step-down type inhibitory avoidance task and tested 24 hr after training, to measure step-down latency. RESULTS: Post-training or pre-test intra-CA1 administration of the cannabinoid receptor agonist, WIN 55,212-2 (0.25 and 0.5 ug/rat) induced amnesia. Amnesia produced by post-training WIN55,212-2 (0.5 ug/rat) was reversed by pre-test administration of WIN55,212-2, that was due to a state-dependent effect. Pre-test intra-CA1 microinjections of clonidine (0.25, 0.5 and 1 MUg/rat) or yohimbine (0.5, 0.75, and 1 MUg/rat) did not affect memory retrieval per se. Pre-test intra-CA1 administration of clonidine (0.5 and 1 MUg/rat) or clonidine (0.25, 0.5, and 1 MUg/rat) with an ineffective dose of WIN 55,212-2 (0.25 ug/rat) reversed post-training WIN55,212-2 (0.5 ug/rat,intra-CA1) induced memory impairment. Pre-test intra-CA1 microinjection of yohimbine (1 MUg/rat) before administration of WIN55,212-2 (0.5 ug/rat, intra-CA1), however, dose-dependently inhibited WIN55,212-2 state dependent memory. CONCLUSION: Modulation of alpha2-adrenergic receptors in the dorsal hippocampal CA1 regions can influence WIN55,212-2 induced amnesia and WIN55,212-2 state-dependent learning of an inhibitory avoidance task by pre- or post-synaptic mechanism(s). PMID- 22039844 TI - Rapid low-cost detection of hepatitis C virus RNA in HCV-infected patients by real-time RT-PCR using SYBR Green I. AB - BACKGROUND: We intend to design and validate a low-cost assay for the detection of hepatitis C virus (HCV) RNA using rapid-cycle RT-PCR. The procedure is performed in a closed system with little risk of contamination allowing PCR and product identification to be performed within one or two hours. METHODS: A SYBR Green-based real-time RT-PCR for rapid detection of HCV. Amplicon synthesis was monitored continuously by SYBR Green I, which binds to double stranded DNA during PCR. The PCR products were identified by melting curve analysis. Standard sera with known concentrations of HCV RNA and 150 clinical samples were used to validate our assay. RESULTS: The minimum detection level of our assay was less than 50 IU/mL. The results on 100 plasma samples were comparable with commercial assays. CONCLUSIONS: This method is useful for rapid qualitative detection of HCV infection and particularly suitable for routine diagnostic applications. PMID- 22039845 TI - Management of acquired thrombophilic disorders in 2011: focus on heparin-induced thrombocytopenia, antiphospholipid syndrome, myeloproliferative neoplasms and paroxysmal nocturnal hemoglobinuria. AB - Arterial and venous thrombosis are interrelated disorders at the interplay of platelets and fibrin. Arterial thrombi are platelet-rich and occur at sites vulnerable to atherosclerotic plaque rupture where blood shear rates are high; on the contrary, venous thrombi occur in association with slow blood flow and shear rates. These differences may underlie why anti-platelet agents are more effective in prevention of arterial thrombosis, while anticoagulants are preferred for venous thrombosis. Although some common thrombophilic disorders (e.g., Factor V Leiden, prothrombin gene mutation, etc.) are almost exclusively associated with venous thromboembolism, there are several disorders that are important to consider when caring for patients with both arterial and venous thromboembolism. This article will review the evidence-based management of heparin induced thrombocytopenia with thrombosis, anti-phospholipid antibody syndrome and catastrophic anti-phospholipid antibody syndrome, thrombohemorrhagic manifestations of Philadelphia chromosome-negative chronic myeloproliferative neoplasms including polycythemia vera, essential thrombocythemia and primary myelofibrosis, as well as paroxysmal nocturnal hemoglobinuria. PMID- 22039846 TI - Risk factors for pre-eclampsia: a study in Tehran, Iran. AB - This study evaluated some risk factors for pre-eclampsia, which is one of the most problematic complications of pregnancy. This was a retrospective case control study conducted on 318 pre-eclamptic women (case group) and 318 women who were normotensive at the time of delivery as the control group. Evaluated factors were: maternal age, gestational age, nuliparity, mother's educational status, maternal body mass index (BMI), maternal hemoglobin and blood Rh, familial history of pre-eclampsia, history of pre-eclampsia in a previous pregnancy, marital relations, urinary infection (UTI) during the present pregnancy, season of delivery, and method of contraception. Risk factors for pre-eclampsia were: UTI (P=0.04); history of pre-eclampsia during previous pregnancy (P=0.003), and winter season (P=0.001). Maternal age of more than 20 years, high educational status of mother, parity more than one, and oral contraceptive pills were protective for pre-eclampsia. After adjusting for all possible confounding factors using multiple logistic regression, only preexisting pre-eclampsia (P=0.004) was a risk factor, whereas parity more than three (P=0.007) and anemia (P=0.01) were protective for pre-eclampsia. The rate of cesarean delivery was more common in the pre-eclamptic group (245 cases, 77%) than the control group (85 cases, 26.7%). The one minute Apgar score of neonates less than 8 was more common in the case group (28.6% vs. 47.4%, P<0.001). Gestational age at the time of delivery was lower in the case group (36.48+/-3.4 weeks vs. 37.12+/-3.3 weeks, P<0.001). Awareness of risk factors of pre-eclampsia can help to monitor patients, ensure earlier diagnosis and predict which patients are more likely to develop pre-eclampsia. PMID- 22039847 TI - Glandular odontogenic cyst of the posterior maxilla. AB - The glandular odontogenic cyst is an uncommon developmental odontogenic cyst described as a distinct entity by Gardner et al. in 1988. The Glandular odontogenic cyst occurs more commonly in middle-aged people and has a predilection for the mandible. Only histopathological examinations allow for certain diagnosis of the cyst. The increased recurrence rate can be due to its multilocularity and incomplete removal of the lining following conservative treatment. This article presents a case of glandular odontogenic cyst in a 28 year-old male patient in the posterior region of the maxilla, which is quite rare. PMID- 22039848 TI - Leiomyoma of the adrenal gland presenting as an incidentaloma. AB - This was an unusual case of a primary leiomyoma tumor of the adrenal gland in a 26-year-old woman incidentally found during workup for mild, dull abdominal pain. PMID- 22039849 TI - Photoclinic. Hypoplasia of the left lung and bronchial asthma. PMID- 22039850 TI - A history of leprosy in Iran during the 19th and 20th centuries. AB - From ancient time leprosy has been regarded as a terrifying, stigmatized disease; nevertheless, its cause remained unidentified up to the late 19th century. For centuries numerous leprosy victims worldwide suffered from its morbidity and were socially isolated. The afflicted individuals were segregated because they were considered 'unclean' and had to live in leper colonies, generally under very poor conditions. Physicians believed that leprosy was an incurable, highly contagious, and hereditary disease. In 1873 the Norwegian physician, Gerhard Armauer Hansen (1841-1912), ended the myth of leprosy and discovered its causative agent, known as Mycobacterium leprae. Hansen's discovery was a great triumph in the fight against leprosy. In the 1930's, the first effective antileprosy drug, dapsone, was introduced and in the early 1980's multi-drug therapy was popularized because of high efficacy in resistant cases. Here, we have presented a brief look at the history of leprosy in the world with special focus on the historical account of leprosy in Iran, particularly during the 19th and 20th centuries. PMID- 22039852 TI - At the start of volume 2. PMID- 22039853 TI - Blood parasites of sheep in the Netherlands. II. Babesia motasi (Sporozoa, Babesiidae). AB - Summary A large Babesia species occurs in sheep on the North Sea islands of the Netherlands. The tick Haemaphysalis punctata is a vector. Its pathogenicity appears to be low. It is morphologically similar to a Turkish strain, considered to be B. motasi, which is also transmitted by Haemaphysalis ticks. It differs from the Turkish parasite serologically as well as in cross-immunity tests and in not being effective to goats. There may be a group of morphologically similar parasites with serological differences and different infectivity for sheep and goats. As it is impossible to know which one is to be considered as the original B. motasi, we designate the Dutch parasite as B. motasi (Netherlands). Anaplasma mesaeterum was found to occur on the island of Texel as well as on Ameland, where it had been found initially. PMID- 22039854 TI - Egg production in relation to the results of a long term serological survey of 73 flocks of fowl. AB - Summary Seventy-three flocks of fowl were tested at regular intervals for the presence of precipitins to fowl adenovirus (AV) and infectious bronchitis virus (IBV), haem-agglutinating inhibiting antibodies to BC14 virus, and of agglutinins to Mycoplasma gallisepticum (M.g.) and Mycoplasma synoviae (M.s.). In all the eight flocks affected with Egg Drop Syndrome (EDS '76), egg production problems were associated with increasing numbers of BCI4 virus reactors and AV reactors. In flocks showing production problems other than EDS '76 without any apparent cause, the average percentage of AV reactors increased significantly after the rearing period; this was not true of IBV reactors. BC14 reactors were either absent or present only once, in small numbers and with low titres, during the test period. The average percentage of AV reactors did not increase after the rearing period either in normally producing flocks or in flocks with production problems for which other diseases or dietary errors plausibly accounted for these problems. All this suggests a pathogenic role of AV in production problems. One can conclude from the high percentage of reactors in all groups of flocks that sub-clinical IBV infections are common. The percentage of IBV reactors during the laying period of flocks with EDS '76 was significantly higher than that of normally producing flocks. It is therefore suggested that subclinical IBV infection could be among the factors causing stress, acting as a trigger for EDS '76. All M.g.-infected flocks showed production problems; M.s. infections could not be related to egg production disturbances. PMID- 22039855 TI - Corynebacterium equi in cattle and pigs. AB - Summary The cervical lymph nodes of pigs, the retropharyngeal and submandibular lymph nodes of cattle and faecal samples from both animal species were examined for the presence of Corynebacterium equi. The organism was recovered from 19 (35 per cent) of 54 porcine cervical lymph nodes and from 0 of 54 bovine retropharyngeal and submandibular lymph nodes. Fifteen (50 per cent) of 30 bovine faecal and 11 (35 per cent) of 31 porcine faecal samples yielded C. equi. PMID- 22039856 TI - Osteochondrosis in six breeds of slaughter pigs. AB - Summary The severity and extent of osteochondral lesions have been examined, macroscopically, radiographically as well as histopathologically, in six different breeds of pigs (Belgian Landrace (B), Duroc (D), Dutch Landrace (N), Dutch Yorkshire (G), Hampshire (H) and Pietrain (P)). In these pigs three different levels of feeding were used. Duroc pigs had significantly more severe lesions in the fore limbs than Dutch Landrace (N), Dutch Yorkshire (G), Hampshire (H) and Pietrain (P) pigs, while Belgian Landrace pigs (B) had significant more severe lesions than Dutch Yorkshire (G) pigs. The differences between breeds related more to the degree of severity of the lesions in the articular surfaces of the distal humerus and proximal radius-ulna and in the distal ulnar growth plate than to the presence of the lesions per se. In the hind limbs Belgian Landrace pigs (B) had significantly more severe osteochondral lesions than all other breeds, while Dutch Landrace pigs (N) had significantly more severe lesions than Duroc (D), Dutch Yorkshire (G), Hampshire (H) and Pietran (P) pigs. Pigs with the highest growth rate showed sginificantly more severe osteochondral lesions in the distal ulnar growth plate and in the medial fe,moral condyle than pigs with a more restricted growth rate. PMID- 22039857 TI - Osteochondrosis in six breeds of slaughter pigs. AB - Summary Coefficients of correlation have been calculated between morphological lesion scores of osteochondrosis that were made on the bones of porcine fore and hind limbs and some carcass characteristics. It was found that carcass length, as well as the relative weights of the hams were significantly correlated with the lesions that were observed in the proximal site of the femur and the medial femoral condyle. Despite these significant correlations, the values of the correlation coefficients were too small to be of any use for selection purposes. This applies the whole animal population, consisting of 6 breeds of pigs. It is shown that the coefficients of correlation between the morphological lesion scores of the femur and the relative weights of the hams in some of the individual breeds were much higher, implying a possibility for the prediction of osteochondrosis based on carcass characteristics. PMID- 22039858 TI - Investigations on live vaccines against infectious bursal disease of chicks. AB - Summary Four live virus vaccines against Infectious Bursal Disease (IBD) were studied with regard to their safety, immune response and applicability. None of the vaccines caused clinical symptoms or had an adverse impact on bodyweight. Differences between these vaccins were observed in their effect on the Bursa/ Bodyweight Ratio and the severity of the microscopical lesions of the bursa Fabricii. The immunosuppressive effect of IBD vaccination at one day of age on the response to Newcastle disease vaccine applied was rather low. Three of the four vaccines induced antibodies associated with protection against challenge. Vaccination of SPF rearing chickens by drinking water at an age of 15 weeks produced an antibody response (Agar Gel Precipitin Test) whereas at an age of 23, 32 and 60 weeks it did not. Chickens of all age groups responded serologically to an intramusculair vaccination. A correlation was found between the immunological response and the effect of the vaccines on the bursa Fabricii. PMID- 22039859 TI - Congenital bicuspid stenosis with left ventricular hypoplasia in a kitten. AB - Summary Congenital bicuspid stenosis with left ventricular hypoplasia was diagnosed in a kitten. Clinical weakness, dyspnoea and marked cardiomegaly (X rays) were related to postmortem findings. The cardiomegaly had resulted from an enlargement of the left auricular appendage. It is supposed the cardiomegaly developed after the closing of the foramen ovale. PMID- 22039861 TI - Aza-crown macrocycles as chiral solvating agents for mandelic acid derivatives. AB - A series of new chiral macrocycles containing the trans-1,2-diaminocyclohexane (DACH) subunit and arene- and oligoethylene glycol-derived spacers has been prepared in enantiomerically pure form. Four of the macrocycles have been characterized by X-ray crystallography, which reveals a consistent mode of intramolecular N-H...N hydrogen bonding and conformational variations about the N benzylic bonds. Most of the macrocycles were found to differentiate the enantiomers of mandelic acid (MA) by (1)H NMR spectroscopy in CDCl(3); within the series of macrocycles tested, enantiodiscrimination was promoted by (i) a meta linkage geometry about the arene spacer, (ii) the presence of naphthalene- rather than phenylene-derived arene spacers, and (iii) increasing length of the oligoethylene glycol bridge. (1)H NMR titrations were performed with optically pure MA samples, and the data were fitted to a simultaneous 1:1 and 2:1 binding model, yielding estimates of 2:1 binding constants between some of the macrocycles and MA enantiomers. In several cases, NOESY spectra of the MA:macrocycle complexes show differential intramolecular correlations between protons adjacent to the amine and carboxylic acid groups of the macrocycles and MA enantiomers, respectively, thus demonstrating geometric differences between the diastereomeric intermolecular complexes. The three most effective macrocycles were employed as chiral solvating agents (CSAs) to determine the enantiomeric excess (ee) of 18 MA samples over a wide ee range and with very high accuracy (1% absolute error). PMID- 22039862 TI - Iatrogenic dura mater exposure post-radiotherapy: a management dilemma. PMID- 22039864 TI - Differential effects in mammalian cells induced by chemical mixtures in environmental biota as profiled using infrared spectroscopy. AB - Environmental contaminants accumulate in many organisms and induce a number of adverse effects. As contaminants mostly occur in the environment as mixtures, it remains to be fully understood which chemical interactions induce the most important toxic responses. In this study, we set out to determine the effects of chemical contaminants extracted from Northern Gannet (Morus bassanus) eggs (collected from the UK coast from three sampling years (1987, 1990, and 1992) on cell cultures using infrared (IR) spectroscopy with computational data handling approaches. Gannet extracts were chemically analyzed for different contaminants, and MCF-7 cell lines were treated for 24 h in a dose-related manner with individual-year extracts varying in their polybrominated diphenyl ether (PBDE) to polychlorinated biphenyl (PCB) ratios. Treated cellular material was then fixed and interrogated using attenuated total reflection Fourier-transform IR (ATR FTIR) spectroscopy; resultant IR spectra were computationally analyzed to derive dose-response relationships and to identify biomarkers associated with each contaminant mixture treatment. The results show distinct biomarkers of effect are related to each contamination scenario, with an inverse relationship with dose observed. This study suggests that specific contaminant mixtures induce cellular alterations in the DNA/RNA spectral region that are most pronounced at low doses. It also suggests alterations in the "biochemical-cell fingerprint" of IR spectra can be indicative of mixture exposures. PMID- 22039863 TI - Accuracy of physical activity assessment during pregnancy: an observational study. AB - BACKGROUND: Prenatal physical activity may improve maternal and infant health and lower future disease risk for both mother and baby; however, very few physical activity assessment methods have been validated for use during pregnancy. The purpose of this study was to evaluate the accuracy of a subjective physical activity record (PAR) and an objective activity monitor, against a reference standard to quantify moderate and vigorous physical activity (MVPA) in pregnant women. The reference standard was based on participant interviews to determine if a woman was an exerciser and confirmed with information obtained from the PAR and a heart rate monitor. METHODS: Fifty-two pregnant women completed a physical activity record (PAR) and wore a SenseWear(r) Mini Armband (SWA) activity monitor over a 7-day period at 18 weeks gestation. Total minutes spent in MVPA were totaled from both modalities and evaluated against the reference standard using contingency analysis and Pearson's chi-square test to evaluate the number of women meeting minimum prenatal physical activity recommendations (at least 3, 30 minute sessions of exercise per week). Both modalities were also tested individually and collectively to assess their ability as indicators of activity using empirically determined cut-offs as indicated by receiver-operator characteristic curves. These experimentally-derived criteria were also tested with Pearson's chi-square test. RESULTS: According to the reference standard, 13 of 52 participants (25%) met the criterion of 3, 30 minute sessions of volitional, moderate-intensity activity. When compared to the reference standard, both the PAR and SWA overestimated exercise status; 42 (81%) and 52 (100%) participants, respectively, achieved 90 minutes of MVPA (P < 0.0001 for both comparisons). Single-modality predictors of MVPA did not show a significant correlation. A composite predictor of MVPA offered the most favorable option for sensitivity and specificity (true positives, n = 8 and true negatives, n = 36) using cut-offs of 280 and 385 minutes/week for the PAR and SWA, respectively. CONCLUSION: Compared to the reference standard, time spent in MVPA obtained from the PAR or SWA overestimated the prevalence of women meeting prenatal exercise recommendations. The most accurate predictor of women meeting current prenatal exercise guidelines was identified by using the PAR and SWA collectively. PMID- 22039865 TI - Metal containing complexes with anticancer properties. PMID- 22039866 TI - Molecular mechanisms and proposed targets for selected anticancer gold compounds. AB - Nowadays, gold compounds constitute a family of very promising experimental agents for cancer treatment. Indeed, several gold(I) and gold(III) compounds were shown to manifest outstanding antiproliferative properties in vitro against selected human tumor cell lines and some of them performed remarkably well even in tumor models in vivo. Notably, the peculiar chemical properties of the gold centre impart innovative pharmacological profiles to gold-based metallodrugs most likely in relation to novel molecular mechanisms. The precise mechanisms through which cytotoxic gold compounds produce their biological effects are still largely unknown. Within this frame, the major aim of this review is to define the possible modes of action and the most probable biomolecular targets for a few representative gold compounds on which extensive biochemical and cellular data have been gathered. In particular, we will focus on auranofin and analogues, on gold(III) porphyrins and gold(III) dithiocarbamates. For these three families markedly distinct molecular mechanisms were recently invoked: a direct mitochondrial mechanism involving thioredoxin reductase inhibition in the case of the gold(I) complexes, the influence on some apoptotic proteins--i.e. MAPKs and Bcl-2--for gold(III) porphyrins, and the proteasome inhibition for gold(III) dithiocarbamates. In a few cases the distinct mechanisms may overlap. The general perspectives for the development of new gold compounds as effective anticancer agents with innovative modes of action are critically discussed. PMID- 22039867 TI - Platinum formulations as anticancer drugs clinical and pre-clinical studies. AB - This review summarizes clinical and pre-clinical results on platinum anti-cancer drug formulations. A concise summary of the use of oxidation state to modulate cancer pharmacology is given for Pt(IV) complexes, distinct from the clinically used Pt(II) drugs. The chemistry of platinum drug formulation combines aspects of kinetics of active moiety release from nominally weak-binding ligands (bond cleavage from platinum-carboxylate and platinum-phosphate) in polymers and nanoparticles with pharmacological considerations of plasma distribution and cellular accumulation. The action of any molecular entity as a drug is influenced by its ADME profile--absorption, distribution, metabolism and excretion. The purpose of drug formulation is to alter any or all of these parameters with the ultimate goal of improving the efficacy and reducing side effects with the possibility to target drugs directly to the tumor site. The diverse array of approaches includes liposomes, polymers (not limited to peptides, dendrimers, biodegradable polymers, polysaccharides, and metallic nanoparticles). Functionalization of the surfaces of nanoparticles with antibodies or cellular surface recognition motifs may further target specific cancers. PMID- 22039868 TI - Bioanalytical and biophysical techniques for the elucidation of the mode of action of metal-based drugs. AB - Platinum-based drugs present one of the pillars of anticancer chemotherapy, and pharmaceuticals incorporating metals such as ruthenium, gallium, titanium and gold, some of which have already entered clinical trials, show promising features including activity against platinum-resistant tumors and/or reduced side-effects. The mode of action of these novel metallodrugs has only been partly elucidated, and even for established treatments, some questions concerning the interactions with targets such as DNA and proteins on a molecular level remain unanswered. In order to tackle the challenging problem of characterizing the behavior of metallodrugs in complex biological media and tissues in vitro and in vivo, bioanalytical and biophysical methodologies are employed. The current state of these techniques, their strengths and limitations, and the information they can provide for achieving this demanding goal, are described in this review. PMID- 22039869 TI - Anticancer platinum (IV) prodrugs with novel modes of activity. AB - Over the past four decades, the search for improved platinum drugs based on the classical platinum (II)-diam(m)ine pharmacophore has yielded only a handful of successful candidates. New methodologies centred on platinum (IV) complexes, with better stability and expanded coordination spheres, offer the possibility of overcoming limitations inherent to platinum (II) drugs. In this review, novel strategies of targeting and killing cancer cells using platinum (IV) constructs are discussed. These approaches exploit the unique electrochemical characteristics and structural attributes of platinum (IV) complexes as a means of developing anticancer prodrugs that can target and selectively destroy cancer cells. Anticancer platinum (IV) prodrugs represent promising new strategies as targeted chemotherapeutic agents in the ongoing battle against cancer. PMID- 22039870 TI - Metal-based antioxidants--potential therapeutic candidates for prevention the oxidative stress-related carcinogenesis: mini-review. AB - The oxidative stress that is associated with the abnormal level of reactive oxygen species (ROS) is considered to be involved in the carcinogenesis process. The antioxidative defense system in the living organism regulates the toxic impact of ROS and there is strong evidence that the antioxidants prevent carcinogenesis. This review will focus on a novel approach to design synthetic metal-based antioxidants and to study their in vitro, ex vivo and in vivo activities in the cellular oxidation processes that might be involved in promotion of carcinogenesis. The antioxidants are divided into several groups depending on the nature of the ligands used: 2,6-dialkylphenols, flavonoids, polyphenols, peptides, purines, pyridines and their derivatives. Some currently achieved results in testing metal complexes as antioxidants show that they could potentially facilitate the scavenging of excess ROS, and thus restore redox balance in the damaged cells and organs. Therefore there is a strong need of the design of novel potential therapeutic candidates for prevention the oxidative stress-related carcinogenesis based on metal complexes. PMID- 22039871 TI - Polynuclear ruthenium, osmium and gold complexes. The quest for innovative anticancer chemotherapeutics. AB - Polynuclear compounds are a relatively new and successful approach in metal-based cancer chemotherapy as typified by the trinuclear Pt compound BBR3464 which was evaluated in clinical trials. In this review, we discuss newer developments of polynuclear ruthenium, osmium and gold complexes, focusing on their anticancer activity. The compounds presented are often supposed to exert their anticancer activity by different modes of action as compared to established drugs, including newly proposed mechanisms such as enzyme inhibition, crosslinking of biomacromolecules or through photo-activation, though many of the examples are also capable of binding to DNA nucleobases. Important metabolization and chemical characteristics of such compounds are discussed, and if the appropriate data is available, molecular modes of action are highlighted. PMID- 22039872 TI - Non-classical structures among current platinum complexes with potential as antitumor drugs. AB - The potential and limitations of the non classical metallodrugs with platinum as metal are discussed in this section, focusing not only in their design but in their mechanism of action and interaction with other biomolecules to introduce and encourage the readers on the potential of this field. PMID- 22039873 TI - Interactions of metal ions with DNA, its constituents and derivatives, which may be relevant for anticancer research. AB - In this review several types of interactions between metal ions and DNA are given, starting from basic binding to the use of metal complexes in cancer treatment and diagnostics. Metal cations help to neutralize the negative charge of DNA and thus enable the normal functions of DNA but many other interactions are also possible and are discussed in this paper. Various consequences of such interactions can be reversible (e. g. conformational changes) or irreversible (e. g. cleavage). It is known that some metal ions can also damage DNA which can provoke mutations and in some cases leads to cancer. It is clear that we know a lot about metal-DNA interactions but much more information is needed to understand the role of metal ions completely and to use this knowledge successfully. PMID- 22039874 TI - The medicinal chemistry of hybrid-based drugs targeting multiple sites of action. PMID- 22039875 TI - Hybrid-based multi-target ligands for the treatment of Alzheimer's disease. AB - Progresses in medicinal chemistry over the last few years have focused on the design and synthesis of hybrid compounds, molecules encompassing in a single scaffold two pharmacophores from known entities endowed with well established biological activities. The interest in this topic is related to the increasing emphasis on the identification of the different factors involved in a number of disorders, such as the complex multifactorial Alzheimer's disease (AD), and hybrid- based strategy has become a focal point in this medicinal chemistry field since it could lead to derivatives with an improved biological profile. Using this strategy, acetylcholinesterase inhibitors (AChEIs) have been extensively coupled with properly selected bioactive molecules to obtain homo- and heterodimers endowed with increased potency together with supplementary actions. In the past decade the inhibition of the AChE induced aggregation of the -amyloid peptide into the senile plaques, which is a key event in the neurotoxic cascade of AD, has been considered a relevant approach leading to several dual binding site inhibitors, able to contact both the peripheral anionic site of AChE and the active site. In recent years, pioneering efforts have been performed to obtain novel AChEIs that, beyond the capability to inhibit AChE, were able to hit a number of specific AD targets. In particular, these compounds proved to possess antioxidant, anti-inflammatory, or neuroprotective activities, useful to block or revert the progression of the disease. This review summarizes the progresses that have been made in the design of hybrid molecules for the treatment of AD. PMID- 22039876 TI - A hydrazide linker strategy for heterobivalent compounds as ortho- and allosteric ligands of acetylcholine-binding proteins. AB - The occurrence of orthosteric and allosteric binding sites is a characteristic common feature of several acetylcholine- binding proteins, like acetylcholinesterase or the nicotinic and muscarinic acetylcholine receptors. These proteins are involved in a number of neurological disorders, such as Alzheimer's disease, and represent important therapeutic targets for the development of heterodimeric ligands addressing both of their binding sites. Among the pharmacophores, which have been combined in such heterodimers, the tetrahydroacridine derivative tacrine has attracted particular interest. This review discusses the chemistry behind the linker connection of tacrine to other pharmacophores and summarizes the types of linkers established to date. Especially, the development of a hydrazide linker for tacrine-derived heterodimers is highlighted by applications in the inhibition of cholinesterases, the bivalent binding to nicotinic and muscarinic acetylcholine receptors, as well as the histochemical imaging of acetylcholinesterase and amyloid-beta. PMID- 22039877 TI - Epigenetic multiple modulators. AB - The development of ligands that as single chemical entities are able to modulate multiple epigenetic targets simultaneously (designed epigenetic multiple ligands) is still in its infancy. We are witnessing some advances with combinations of the fused or linked pharmacophores of an epi-drug and other anticancer agents. More recently, however, a very promising approach has been developed in which a single chemical entity exerts several therapeutic activities simultaneously, such as a compound that inhibits several epigenetic enzymes and as a consequence displays multiple biological profiles that address synergistically a particular multifactorial disease. Despite their promiscuity, these multiple epigenetic ligands have exciting conceptual advantages, as they (i) lower the risk of drug drug interactions compared to cocktails or multicomponent drugs and facilitate ADMET and toxicology studies, (ii) minimize the development of drug resistance, (iii) exploit synergies between the targeted pathways/factors and (iv) can generally be used at lower therapeutically effective concentrations than the single target drugs. The obvious problem with such compounds is to find/design drugs which target multiple effectors with high selectivity and efficiency without displaying extensive off-target effects. In addition, the rational design of multiple epi-ligands is a major challenge. In this review we provide structurally-based principles and the optimization of activities towards the different epigenetic targets. PMID- 22039878 TI - Lights and shadows on monoamine oxidase inhibition in neuroprotective pharmacological therapies. AB - Playing a pivotal role in the metabolism of neurotransmitters in the central nervous system, the mitochondrial enzymes monoamine oxidases A and B (MAO A and B) have been for long studied as drug targets for neurodegenerative and neurological diseases. MAO inhibitors (MAOIs) are clinically used to treat Parkinson's disease and depression by blocking the degradation of neuroactive catecholamines and providing a symptomatic relief in the patients. More recent is the idea that the neuroprotective effect of MAOIs may result from the prevention of oxidative stress produced by the MAO reaction rather than being simply related to the inhibition of neurotransmitters degradation. Tranylcypromine and phenelzine are among the first developed MAOI drugs and have been used for years to treat depression. Their usage is now limited to cases of refractory depression because of their negative side effects, which are due to both the lack of MAO A/MAO B selectivity and the inhibition of other enzymes such as the drug metabolizing cytochromes P450. Although the multi-target action of these MAOIs determines negative implications, the most newly developed compounds have improved properties not only for their specificity relatively to MAO A/MAO B selectivity but also because they function through multiple mechanisms that produce beneficial effects. In particular, safinamide, a MAO B selective inhibitor in clinical trials for Parkinson's disease, is neuroprotective by blocking the voltage-dependent Na+ and Ca2+ channels and the Ca2+-mediated glutamate release processes. Rasagiline is a drug used in combination with L-dopa in the treatment of parkinsonian patients and the metabolic products of its degradation exert neuroprotective effects. Moreover, rasagiline scaffold is used to design analogs by addition of pharmacophores that act on other neurological targets. This multi-target approach may prove successful in order to find new and more effective therapies for the complexity of neurodegenerative diseases. PMID- 22039879 TI - Multitarget-directed ligands: innovative chemical probes and therapeutic tools against Alzheimer's disease. AB - Multitarget agents directed at selected molecular targets involved in the pathogenic cascade of Alzheimer's disease (AD) have been increasingly sought after in recent years, with the aim of achieving enhanced therapeutic efficiency with respect to single-target drugs and drug candidates. At the same time, much attention has been devoted to identifying high quality pharmacological tools to help explore the molecular mechanisms underlying AD without being exposed to physicochemical challenges. Herein, we discuss several examples of both types of compounds, taken from our own research and derived from the leads memoquin, lipocrine and bis(7)tacrine. PMID- 22039880 TI - Multi-target-directed ligands as innovative tools to combat trypanosomatid diseases. AB - Of the tropical diseases, trypanosomiases and leishmaniases should most concern the pharmaceutical community because of their high prevalence in developing countries and the lack of effective drug treatments. Despite this, they have not historically received much attention in terms of investment and research effort, nor do they now. In very recent years, thanks to the involvement of several nonprofit organizations, the chemotherapeutic options have expanded with the introduction of the first combination therapy. The optimal efficacy and safety of nifurtimox-eflornithine combination against second-stage human African trypanosomiasis is an encouraging first step towards simpler and more affordable therapies. Along the same line, I propose that single chemical entities able to modulate more than one target may prove more efficacious and tolerable than the available arsenal of drugs. Herein, I discuss the pros and cons of this approach, together with examples taken from the recent literature. PMID- 22039881 TI - 1,8-Naphthyridine derivatives as cholinesterases inhibitors and cell Ca2+ regulators, a multitarget strategy for Alzheimer's disease. AB - The synthesis and the pharmacological evaluation of 1,8-naphthyridine derivatives and related compounds as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as voltage-dependant Ca(2+) channels (VDCC) modulators of are summarized. These compounds are closely related to the anticholinesterasic tacrine and the well-known Ca(2+)-antagonists 1,4 dihydropyridines. They were obtained from polyfunctionalized 2-amino-3 cyanoheterocycles via Friedlander-type reaction with selected cycloalkanones. Most of the compounds showed moderate inhibitory activity of cholinesterases, with selectivity to the AChE inhibition, and blocked Ca(2+) channels, preferentially the L-subtype, when a 4-aryl-1,4-DHP-like moiety were present in its chemical structure. Taking into account that the regulation of Ca(2+) entry to cells has been described to play a key role in cell death/survival processes, some of them were studied as cytoprotective agentes against different toxic stimuli. Specifically, the 1,8-naphthyridine derivative 30 was described to exert a tiny positive effect on Ca(2+) entry to cells, as single cell, isolated organ, and (45)Ca(2+) uptake experiments showed. This slight "Ca(2+)-promoter" behavior was related to its cytoprotective effect against several toxic stimuli, as Ca(2+) chelating and antiapoptotic protein Bcl-2 was overexpressed in bovine chromaffin cells preincubated with 30. In fact, the relationship between small elevations of [Ca(2+)](c) and neuroprotection has been deeply studied by our group and others, concluding that a huge blockade of Ca(2+) entry does not have to generate neuroprotection, but the precise regulation, up or down, of such [Ca(2+)] concentrations. PMID- 22039882 TI - Multitarget antithrombotic drugs. AB - Thromboembolic disorders are still the leading causes of morbidity and mortality in developed societies. Therefore, prophylaxis and treatment of arterial and venous thrombosis are among the main therapeutic challenges nowadays. Simultaneous action on several targets involved in pathology of thrombosis offers potential advantages compared to existing drugs which were developed as selective modulators of single targets. The review focuses on dual inhibitors of coagulation enzymes, dual antiaggregatory compounds exerting their action on different combinations of platelet targets, as well as on anticoagulant/antiaggregatory compounds which interfere with at least one target involved in blood coagulation and at least one target engaged in the process leading to platelet aggregation. PMID- 22039884 TI - Experiences of Syrian women with breast cancer regarding chemotherapy: a qualitative study. AB - The purpose of this study was to explore the experiences of Syrian women with breast cancer regarding their chemotherapy. A qualitative design, based on the content analysis approach, was used for the data collection and analysis of the perspectives of women with breast cancer in Syria. Semistructured interviews were carried out with 17 women who underwent chemotherapy after mastectomy in a chemotherapy center in Latakia between June and October 2010. Four main themes emerged from the study: psychological discomfort (negative emotion, body image, and depressive symtoms), physical problems (acute consequences of chemotherapy and general aspects of chemotherapy), social dysfunction (social isolation and lack of marriage opportunites), and failure in the family role (mother role and sexual relationship). Understanding the experiences of women with breast cancer regarding chemotherapy enables nurses to devise appropriate strategies to provide better support and care to patients in order to improve their quality of life. PMID- 22039883 TI - Targeting a DNA binding motif of the EVI1 protein by a pyrrole-imidazole polyamide. AB - The zinc finger protein EVI1 is causally associated with acute myeloid leukemogenesis, and inhibition of its function with a small molecule therapeutic may provide effective therapy for EVI1-expressing leukemias. In this paper we describe the development of a pyrrole-imidazole polyamide to specifically block EVI1 binding to DNA. We first identify essential domains for leukemogenesis through structure-function studies on both EVI1 and the t(3;21)(q26;q22)-derived RUNX1-MDS1-EVI1 (RME) protein, which revealed that DNA binding to the cognate motif GACAAGATA via the first of two zinc finger domains (ZF1, encompassing fingers 1-7) is essential transforming activity. To inhibit DNA binding via ZF1, we synthesized a pyrrole-imidazole polyamide 1, designed to bind to a subsite within the GACAAGATA motif and thereby block EVI1 binding. DNase I footprinting and electromobility shift assays revealed a specific and high affinity interaction between polyamide 1 and the GACAAGATA motif. In an in vivo CAT reporter assay using NIH-3T3-derived cell line with a chromosome-embedded tet inducible EVI1-VP16 as well as an EVI1-responsive reporter, polyamide 1 completely blocked EVI1-responsive reporter activity. Growth of a leukemic cell line bearing overexpressed EVI1 was also inhibited by treatment with polyamide 1, while a control cell line lacking EVI1 was not. Finally, colony formation by RME was attenuated by polyamide 1 in a serial replating assay. These studies provide evidence that a cell permeable small molecule may effectively block the activity of a leukemogenic transcription factor and provide a valuable tool to dissect critical functions of EVI1 in leukemogenesis. PMID- 22039885 TI - Medical simulation for professional development--science and practice. AB - From the earliest days of medical practice, when surgeons used cadavers to explore the possibilities of surgical intervention, simulation has been employed to advance the practice of health care. In the last 10 years, technological advances have allowed for a wider availability and greater realism of simulation, and this has encouraged a great expansion in its use. Simulation aims to create a virtuous cycle of professional development to improve patient outcomes. Although it seems eminently logical to believe that simulation will result in better outcomes, there is a need to test these new training interventions rigorously to be sure of their worth and to understand any limitations. The purpose of this BJOG supplement is to examine in depth several paradigms of medical simulation within maternity care and gynaecology, in different settings, looking at what can be achieved and how. In this opening review, we look at the potential use of medical simulation in broad terms and describe the types of evidence that can be employed to support its use. PMID- 22039886 TI - Integration of laparoscopic virtual-reality simulation into gynaecology training. AB - Surgery carries the risk of serious harm, as well as benefit, to patients. For healthcare organisations, theatre time is an expensive commodity and litigation costs for surgical specialities are very high. Advanced laparoscopic surgery, now widely used in gynaecology for improved outcomes and reduced length of stay, involves longer operation times and a higher rate of complications for surgeons in training. Virtual-reality (VR) simulation is a relatively new training method that has the potential to promote surgical skill development before advancing to surgery on patients themselves. VR simulators have now been on the market for more than 10 years and, yet, few countries in the world have fully integrated VR simulation training into their gynaecology surgical training programmes. In this review, we aim to summarise the VR simulators currently available together with evidence of their effectiveness in gynaecology, to understand their limitations and to discuss their incorporation into national training curricula. PMID- 22039887 TI - Practical simulation training for maternity care--where we are and where next. AB - Improving maternal and perinatal care is a global priority. Practical simulation training for maternity care might prevent many of these deaths. There have been numerous evaluation studies published on the effectiveness of simulation training for obstetric emergencies, with increasing evidence that it is associated with improvement in clinical outcomes. Evidence has begun to move from subjective assessment of participants' experiences towards objective assessment of clinical outcomes. However, the results are not entirely consistent and, at present, all of the evidence associating training with improvements in clinical outcomes relates to neonatal outcomes. This review summarises recent progress in the evaluation of the effectiveness of simulation training for maternity care in both high- and low-resource settings, and presents a vision for ensuring that practical simulation training for maternity care can become an effective tool to reduce global maternal and perinatal morbidity and mortality. PMID- 22039888 TI - Serious gaming in women's health care. AB - Computer-based (serious) gaming is a new field in medical education, which has the potential to become an important tool for healthcare professionals for learning a range of clinical skills. To evaluate the current status of serious gaming in medicine, we performed a systematic literature review. In June 2011, we undertook a search in PubMed and Embase databases with the MeSH terms video games, education, training, gaming and healthcare. Thirty relevant papers were identified, reviewed and summarised. The studies showed that serious gaming is a stimulating learning method and that students are enthusiastic about its use. Studies have shown that previous recreational gaming is associated with greater surgical skill, especially for laparoscopy. In addition to surgical skills, serious gaming is potentially a good method for learning clinical decision-making and patient interaction. Games are already being developed for teaching specific clinical skills, for example in cardiology and orthopaedics for example. Initial studies suggest that serious gaming is likely to be an effective training method; however, there is a paucity of studies showing the conclusive clinical benefit of serious gaming. Future studies should focus on demonstrating the clinical effectiveness of serious gaming on skills used in patient care. PMID- 22039889 TI - Sustaining simulation training programmes--experience from maternity care. AB - There is little scientific evidence to support the majority of simulation-based maternity training programmes, but some characteristics appear to be associated with sustainability. Among these are a clear institutional-level commitment to the course, strong leadership in course organisation, a curriculum relevant to clinical practice, a nonthreatening learning environment, the establishment of multiprofessional training and the use of simulators appropriate to the learning objectives. There is still some debate on whether simulation-based sessions should be carried out in dedicated training time outside normal working hours or in ad-hoc drills that are run during clinical sessions, whether they should be located in clinical areas, simulation centres, or both, and whether or not they should include standardised generic teamwork training sessions. In this review, we discuss the main characteristics that appear to make a simulation-based training programme a sustainable initiative. PMID- 22039890 TI - Identification of novel antitubulin agents by using a virtual screening approach based on a 7-point pharmacophore model of the tubulin colchi-site. AB - Tubulin inhibition represents an established target in the field of anticancer research, and over the last 20 years, an intensive search for new antimicrotubule agents has occurred. Indeed, in silico models have been presented that might aid the discovery of novel agents. Among these, a 7-point pharmacophore model has been recently proposed. As a formal proof of this model, we carried out a ligand based virtual screening on the colchicine-binding site. In vitro testing demonstrated that two compounds displayed a cytotoxic profile on neuroblastoma cancer cells (SH-SY5H) and one had an antitubulinic profile. PMID- 22039891 TI - Analysis of porcine MUC4 gene as a candidate gene for prolificacy QTL on SSC13 in an Iberian * Meishan F2 population. AB - BACKGROUND: Reproductive traits, such as prolificacy, are of great interest to the pig industry. Better understanding of their genetic architecture should help to increase the efficiency of pig productivity through the implementation of marker assisted selection (MAS) programmes. RESULTS: The Mucin 4 (MUC4) gene has been evaluated as a candidate gene for a prolificacy QTL described in an Iberian * Meishan (Ib * Me) F2 intercross. For association analyses, two previously described SNPs (DQ124298:g.243A>G and DQ124298:g.344A>G) were genotyped in 347 pigs from the Ib * Me population. QTL for the number of piglets born alive (NBA) and for the total number of piglets born (TNB) were confirmed on SSC13 at positions 44 cM and 51 cM, respectively. The MUC4 gene was successfully located within the confidence intervals of both QTL. Only DQ124298:g.344A>G MUC4 polymorphism was significantly associated with both NBA and TNB (P-value < 0.05) with favourable effects coming from the Meishan origin. MUC4 expression level was determined in F2 sows displaying extreme phenotypes for the number of embryos (NE) at 30-32 days of gestation. Differences in the uterine expression of MUC4 were found between high (NE >= 13) and low (NE <= 11) prolificacy sows. Overall, MUC4 expression in high prolificacy sows was almost two-fold increased compared with low prolificacy sows. CONCLUSIONS: Our data suggest that MUC4 could play an important role in the establishment of an optimal uterine environment that would increase embryonic survival during pig gestation. PMID- 22039893 TI - Micro-photoluminescence of GaAs/AlGaAs triple concentric quantum rings. AB - A systematic optical study, including micro, ensemble and time resolved photoluminescence of GaAs/AlGaAs triple concentric quantum rings, self-assembled via droplet epitaxy, is presented. Clear emission from localized states belonging to the ring structures is reported. The triple rings show a fast decay dynamics, around 40 ps, which is expected to be useful for ultrafast optical switching applications. PMID- 22039892 TI - Monitoring fever treatment behaviour and equitable access to effective medicines in the context of initiatives to improve ACT access: baseline results and implications for programming in six African countries. AB - BACKGROUND: Access to artemisinin-based combination therapy (ACT) remains limited in high malaria-burden countries, and there are concerns that the poorest people are particularly disadvantaged. This paper presents new evidence on household treatment-seeking behaviour in six African countries. These data provide a baseline for monitoring interventions to increase ACT coverage, such as the Affordable Medicines Facility for malaria (AMFm). METHODS: Nationally representative household surveys were conducted in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia between 2008 and 2010. Caregivers responded to questions about management of recent fevers in children under five. Treatment indicators were tabulated across countries, and differences in case management provided by the public versus private sector were examined using chi-square tests. Logistic regression was used to test for association between socioeconomic status and 1) malaria blood testing, and 2) ACT treatment. RESULTS: Fever treatment with an ACT is low in Benin (10%), the DRC (5%), Madagascar (3%) and Nigeria (5%), but higher in Uganda (21%) and Zambia (21%). The wealthiest children are significantly more likely to receive ACT compared to the poorest children in Benin (OR = 2.68, 95% CI = 1.12-6.42); the DRC (OR = 2.18, 95% CI = 1.12-4.24); Madagascar (OR = 5.37, 95% CI = 1.58-18.24); and Nigeria (OR = 6.59, 95% CI = 2.73-15.89). Most caregivers seek treatment outside of the home, and private sector outlets are commonly the sole external source of treatment (except in Zambia). However, children treated in the public sector are significantly more likely to receive ACT treatment than those treated in the private sector (except in Madagascar). Nonetheless, levels of testing and ACT treatment in the public sector are low. Few caregivers name the national first line drug as most effective for treating malaria in Madagascar (2%), the DRC (2%), Nigeria (4%) and Benin (10%). Awareness is higher in Zambia (49%) and Uganda (33%). CONCLUSIONS: Levels of effective fever treatment are low and inequitable in many contexts. The private sector is frequently accessed however case management practices are relatively poor in comparison with the public sector. Supporting interventions to inform caregiver demand for ACT and to improve provider behaviour in both the public and private sectors are needed to achieve maximum gains in the context of improved access to effective treatment. PMID- 22039894 TI - Does rural residence limit access to mental health services? AB - INTRODUCTION: Rural residence may reduce access to specialized mental health services. The objective of this study was to examine the role of rural residence in relation to service utilization. Using Canadian data collected in 2002, service use was examined as a function of the presence of anxiety or mood disorders and rural/urban residence. Use of four different types of professional mental health services was examined in relation to rural residence and additional demographic, social, and health status factors known to predict use of services. METHODS: Data were obtained from Statistics Canada's Canadian Mental Health Survey Cycle 1.2. Rural residence was defined as living in a rural community with a population of 1000 or less. For all participants, associations between the presence of anxiety or mood disorders, rural/urban residence, and any service use or use of specialized mental health services (psychiatry and psychology) were examined. For participants who had used professional services, associations were examined between 17 predictor variables, including location of residence, and the use of four types of service providers (family doctor or GP; nurse, social worker, counsellor, or psychotherapist; psychiatrist; or psychologist). Predictors included demographic, social, and health status variables. Cross tabulated counts and adjusted odds ratios with 99% confidence intervals based on bootstrapped variance estimates were used to evaluate predictors. RESULTS: Among the total sample (n = 35 140), 7.9% had used professional mental health services in the previous year. Among people who were likely to have had anxiety or mood disorders, rural or urban residence was not differentially related to past-year use of any professional services or specialized mental health services. Multivariate logistic regression was used to model factors predicting past year use of four different types of professional services. Location of residence was not a significant predictor of service utilization. Age, sex, race, level of education, degree of psychological distress, chronicity of distress, and the presence of anxiety or mood disorders predicted type of service used. CONCLUSIONS: The notion that rural residence limits access to mental health services was not supported. Other demographic and health status indicators such as age, sex, race, education, distress, and type of illness were more important predictors of service utilization. However, null findings related to geographic residence must be interpreted cautiously due to the small sample of rural residents who sought mental health services. The mental health system in Canada must provide a variety of professional services in order to meet the preferences of diverse groups, and mental health specialists must find ways to adequately support general practice physicians and counsellors who provide mental health services. PMID- 22039895 TI - The importance of hearing evaluation in the study of simulated visual impairment in speech reading abilities. PMID- 22039896 TI - Pressure ulcers: knowledge and attitude of nurses and nursing assistants in Belgian nursing homes. AB - AIMS: To gain insight into the knowledge and attitudes of nurses and nursing assistants and to study the correlation between knowledge, attitudes and the compliance with the pressure ulcer prevention guidelines provided to residents at risk of pressure ulcers in nursing homes. BACKGROUND: There is a lack of evidence on knowledge and attitudes of nurses and nursing assistants towards pressure ulcer prevention in nursing homes. DESIGN: A cross-sectional multi-centre study. METHODS: A convenience sample of nine Belgian nursing homes, representing 18 wards was chosen in the study. In total, 145 nurses and nursing assistants were included. The compliance with the guidelines was evaluated in 615 residents, and data were collected using validated instruments. RESULTS: Fully compliant prevention was found in only 6.9% of the residents at risk. The mean knowledge score of the nurses was 29.3 vs. 28.7% for the nursing assistants. The overall attitude score was 74.5%, and attitude scores were significantly different between nurses and nursing assistants. Nurses showed to have a more positive attitude towards pressure ulcer prevention than nursing assistants, respectively 78.3 and 72.3%. A more positive attitude was a significant predictor of pressure ulcer prevention compliance with the guidelines provided to residents at risk of pressure ulcers in nursing homes. CONCLUSIONS: Knowledge about pressure ulcer prevention of both nurses and nursing assistants in nursing homes was low. Attitudes were a significant predictor of the application of fully compliant prevention in residents at risk. RELEVANCE TO CLINICAL PRACTICE: Pressure ulcer prevention is an important aspect in daily care for residents at risk in nursing homes. These insights will contribute to evidence-based practice in this area of care and will form the basis for the development of an education strategy for pressure ulcer prevention and management in nursing homes. PMID- 22039898 TI - Indirect fluorescence antibody studies of porcine cytomegalo virus infections in the Netherlands. AB - Summary Sera from 683 pigs of 41 swine herds with clinical atrophic rhinitis (A R), from 477 pigs of 37 herds with no A R history, from 267 breeding sows and breeding boars for slaughtering, from 22 boars at an artifical insemination centre, and from 103 SPF pigs were tested for the presence of antibodies to porcine cytomegalo virus (PCMV). The herds examined were spread all over the Netherlands. For the presence of antibodies to PCM V the indirect fluorescence antibody test was used. To obtain the antigen, the PCMV had been grown in pig lung macrophage cultures in Petri dishes for 10-12 days. These macrophages were dropped into the wells of slides. The serum dilution 1:20 of all the 103 sera from SPF pigs were negative, but 93 per cent of the other sera were positive. No marked differences were found between swine herds with clinical atrophic rhinitis and herds with no A R history. The FA titres in both types of herds seem to be at a comparable level. PMID- 22039897 TI - Green tea and theanine: health benefits. AB - Historically, the medicinal use of green tea dates back to China 4700 years ago and drinking tea continues to be regarded traditionally in Asia as a general healthful practice. Numerous scientific publications now attest to the health benefits of both black and green teas, including clinical and epidemiological studies. Although all tea contains beneficial antioxidants, high-quality green and white teas have them in greater concentrations than black tea. Today, scientists believe that the main active ingredients of green tea include the polyphenols, in particular the catechins and the amino acid, theanine. Studies on the health benefits of drinking tea, particularly green tea, are finding exciting results, particularly in cancer research. Modern studies in both Asia and the West have provided encouraging results indicating that drinking green tea contributes to fighting many different kinds of cancers including stomach, oesophageal, ovarian and colon. Recent studies describing the health benefits of these compounds will be reviewed. PMID- 22039899 TI - Feline mammary tumours and dysplasias conclusions based on personal studies and some suggestions for future research. AB - Summary Feline mammary tumours and dysplasias were studied by various methods: morphological, electron-microscopical, immunological and virological. The most important conclusion was that cats with mammary tumours (benign and malignant tumours and lesions, the significance of which is not known so far) may be suitable animal models for the study of certain features of human mammary tumours; for instance, the study of the relationship between particular histological and biological characteristics of mammary carcinoma and the prognosis; the study of the question whether a virus (or viruses) does (do) or does (do) not play a role in the pathogenesis or growth of mammary tumours; the study of the possible presence of specific cellular and/or humoral immunity to mammary tumours and the study of the possible effects of progestogens on the mammary gland. As the study can not be regarded as a self-contained entity, it should be continued; this applies particularly to those parts of the study, that offer the best prospects for comparative investigations. PMID- 22039901 TI - Effect of zinc and molybdenum supplementation of the feed concentrate on the storage of copper in the liver of lambs. AB - Summary During a 98-day trial, eight groups of eight male weanling Texel x Friesian milk sheep lambs were fed the same hay and concentrates, the latter differing only in the contents of Cu, Zn, and Mo. At high (+/- 30 ppm) and moderately low (+/- 15 ppm) copper levels in the concentrates, additions of Zn (respectively 0, 150, and 340 ppm) and Mo (0 and 16 ppm) to the concentrates were studied with regard to effect on the accumulation of copper in the liver. At the higher copper level, the addition of 150 or 340ppm Zn resulted in a significant decrease of the Cu accumulation in the liver, while at a moderately low copper level the effect of these additions on the Cu accumulation was only slight. The two Zn doses given appeared to be equally effective in reducing the Cu accumulation. Additions of zinc did not increase liver and kidney Zn. The addition of Mo. resulted in higher levels of Mo in liver and kidney. At either copper level the addition of 16 ppm Mo was more effective in reducing the Cu accumulation in the liver than the addition of 150 or 340 ppm Zn. The additions of Zn and Mo, had no visible influence on the health of the lambs. This agrees with the finding that the blood parameters (determination of haemoglobin, haematocryt, protein, copper, zinc, enzymes) and the growth of the lambs were in the normal range. These results suggest that zinc may be a useful alternative to the somewhat toxic molybdenum as an additive to concentrates for sheep in preventing Cu intoxication. PMID- 22039900 TI - Skin test as herd diagnosis for Aujeszky's disease (Pseudorabies) in swine. AB - Summary The value of a skin test for the diagnosis of Aujeszky's disease (pseudorabies) in swine was examined. Semipurified and concentrated antigens, obtained by ether/tween 80 inactivation of Aujeszky's disease virus, were inoculated intradermally into seronegative, experimentally infected and vaccinated swine and into pigs with maternal antibodies. A specific skin reaction, characterized by a visible indurated swelling, was observed within 24 hours in animals with active immunity, No reaction was seen in pigs with maternal immunity or in seronegative uninfected and unvaccinated animals. In the infected and vaccinated groups, 89% and 58% respectively of the animals with seroneutralizing antibodies were positive by the skin test response. Positive reactions were observed as early as 8 days after the infection. All but one seronegative animals remained free of antibodies after 2 consecutive skin tests and the course of decline of maternal antibodies was not changed. An earlier skin test did not lead to sensitization for a later application. The present results, together with field experience on 8 farms, revealed that the skin test could be considered a reliable method for diagnosis of Aujeszky's disease in swine on a herd basis. PMID- 22039902 TI - Studies on bovine demodecosis in northern Nigeria. AB - Summary The study reported in the present paper discusses the clinical and histological picture of bovine demodecosis and the morphology of Demodex mites as seen in four cows suffering from generalized demodecosis. There were no clinical signs of other skin affections. Changes in both the number and the appearance of visible skin lesions were seen and related to the level of nutrition and the exposure to sunshine of the cattle. Histological sections of some skin nodules showed the presence of mite colonies in the hair follicles. Only adults were seen in the sebaceous glands. Microscopical study of the morphology of the mites revealed the presence of two types of demodicids in the skin lesions and three types from epilated eyelashes. Morphological criteria are presented to aid in identification of species and of life stages. PMID- 22039903 TI - Squamous cell carcinoma of the equine stomach. AB - Summary Both clinical and pathological features of seven horses suffering from a squamous cell carcinoma of the stomach are presented. The main complaints in the horses, aged six years or more, were loss both of weight and of condition. Metastases had often developed. The diagnostic difficulties and possibilities are discussed. PMID- 22039904 TI - Cyanides and their toxicity: A literature review. AB - Summary Cyanide is a potent and rapidly-acting asphyxiant which prevents tissue utilization of oxygen by inhibition of the cellular respiratory enzyme, cytochrome oxidase. Inhalation or ingestion of cyanide produces reactions within a few seconds and death within minutes. Cyanide toxicity of dietary origin has been implicated in acute animal deaths and as major etiologic factors in toxic ataxic neuropathy in man and as a cause of vision failure in humans suffering from tobacco amblyopia and leber's hereditary optic atrophy. Diagnosis of cyanide toxicity may be confirmed by a variety of laboratory procedures, but accurate assay is essential for proper conclusions from analysis of animal tissues several hours after death or from human samples in instances of chronic dietary exposure. Biological detoxification of cyanide is available through several routes, and the application of sodium nitrite with sodium thiosulfate or administration of methylene blue are effective treatment procedure. The environmental availability of cyanide in its various forms necessitates an understanding of its pathophysiology and responsible management of hazardous situations. PMID- 22039905 TI - On some factors influencing the output of the larvae of Prostrongylids of sheep in natural infections. AB - Summary The output of first stage Protostrongvlid larvae of sheep was studied in natural infections. Three sets of observations were obtained from October 1977 to December 1978 in three regions. The larval output varied with the species harboured by sheep and with the density of worm populations. Anthelmintic treatments influenced the fecundity of worms. The age of the animals was an important cause of variation in the size of larval output; a rise of the latter was observed in pregnant ewes at the period of lambing. A seasonal variation in output was recorded. The fauna was characterized by the high prevalence of Muellerius and Neostrongylus. PMID- 22039906 TI - Milk cell count in machine milked dairy goats. AB - Summary Milk samples from 3 machine milked herds with 185 goats were examined for mastitis. Bacteriologically positive results were very few but the cell counts were high. These findings are in contrast to the results obtained with cows' milk samples. PMID- 22039908 TI - Chemoenzymatic synthesis of each enantiomer of orthogonally protected 4,4 difluoroglutamic acid: a candidate monomer for chiral Bronsted acid peptide-based catalysts. AB - We have accomplished an asymmetric synthesis of each enantiomer of 4,4 difluoroglutamic acid. This alpha-amino acid has been of interest in medicinal chemistry circles. Key features of the synthesis include highly scalable procedures, a Reformatsky-based coupling reaction, and straightforward functional group manipulations to make the parent amino acid. Enantioenrichment derives from an enzymatic resolution of the synthetic material. Conversion of the optically enriched compounds to orthogonally protected forms allows for the selective formation of peptide bonds. 4,4-Difluoroglutamic acid, in a suitably protected form, is also shown to exhibit enhanced catalytic activity in both an oxidation reaction and a reduction reaction, in comparison to the analogous glutamic acid derivative. PMID- 22039909 TI - Differential ordering of the protein backbone and side chains during protein folding revealed by site-specific recombinant infrared probes. AB - The time scale for ordering of the polypeptide backbone relative to the side chains is a critical issue in protein folding. The interplay between ordering of the backbone and ordering of the side chains is particularly important for the formation of beta-sheet structures, as the polypeptide chain searches for the native stabilizing cross-strand interactions. We have studied these issues in the N-terminal domain of protein L9 (NTL9), a model protein with mixed alpha/beta structure. We have developed a general approach for introducing site-specific IR probes for the side chains (azide) and backbone ((13)C?(18)O) using recombinant protein expression. Temperature-jump time-resolved IR spectroscopy combined with site-specific labeling enables independent measurement of the respective backbone and side-chain dynamics with single residue resolution. We have found that side chain ordering in a key region of the beta-sheet structure occurs on a slower time scale than ordering of the backbone during the folding of NTL9, likely as a result of the transient formation of non-native side-chain interactions. PMID- 22039911 TI - Two novel frameshift mutations of the DSRAD gene in Chinese pedigrees with dyschromatosis symmetrica hereditaria. AB - BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant disorder characterized by a mixture of hyperpigmented and hypopigmented macules localized on the back of the extremities and caused by the mutations in the DSRAD gene. METHODS: Two Chinese pedigrees of typical DSH were subjected to mutation detection in DSRAD. Direct sequencing of all PCR products of the whole coding regions of DSRAD was performed to identify the mutation. RESULTS: The c.1615delG (p.V539fs) mutation was found in the affected members but not in the healthy individuals in family 1 and the c.ins1372-9 CCACAGAT (p.D458fs) mutation was found in patients but not in the healthy members of family 2. CONCLUSION: Our study found two novel frameshift mutations in the DSRAD gene. We add new variants to the knowledge of DSRAD mutations in DSH. PMID- 22039910 TI - Development and characterization of a novel C-terminal inhibitor of Hsp90 in androgen dependent and independent prostate cancer cells. AB - BACKGROUND: The molecular chaperone, heat shock protein 90 (Hsp90) has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity and resistance resulting from induction of the heat shock response (HSR) has led to both scheduling and administration concerns. Therefore, Hsp90 inhibitors that do not induce the heat shock response represent a promising new direction for the treatment of prostate cancer. Herein, the development of a C-terminal Hsp90 inhibitor, KU174, is described, which demonstrates anti-cancer activity in prostate cancer cells in the absence of a HSR and describe a novel approach to characterize Hsp90 inhibition in cancer cells. METHODS: PC3-MM2 and LNCaP-LN3 cells were used in both direct and indirect in vitro Hsp90 inhibition assays (DARTS, Surface Plasmon Resonance, co-immunoprecipitation, luciferase, Western blot, anti-proliferative, cytotoxicity and size exclusion chromatography) to characterize the effects of KU174 in prostate cancer cells. Pilot in vivo efficacy studies were also conducted with KU174 in PC3-MM2 xenograft studies. RESULTS: KU174 exhibits robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a HSR. Furthermore, KU174 demonstrates direct binding to the Hsp90 protein and Hsp90 complexes in cancer cells. In addition, in pilot in-vivo proof of-concept studies KU174 demonstrates efficacy at 75 mg/kg in a PC3-MM2 rat tumor model. CONCLUSIONS: Overall, these findings suggest C-terminal Hsp90 inhibitors have potential as therapeutic agents for the treatment of prostate cancer. PMID- 22039912 TI - Physicochemical characterization of particulate emissions from a compression ignition engine: the influence of biodiesel feedstock. AB - This study undertook a physicochemical characterization of particle emissions from a single compression ignition engine operated at one test mode with 3 biodiesel fuels made from 3 different feedstocks (i.e., soy, tallow, and canola) at 4 different blend percentages (20%, 40%, 60%, and 80%) to gain insights into their particle-related health effects. Particle physical properties were inferred by measuring particle number size distributions both with and without heating within a thermodenuder (TD) and also by measuring particulate matter (PM) emission factors with an aerodynamic diameter less than 10 MUm (PM(10)). The chemical properties of particulates were investigated by measuring particle and vapor phase Polycyclic Aromatic Hydrocarbons (PAHs) and also Reactive Oxygen Species (ROS) concentrations. The particle number size distributions showed strong dependency on feedstock and blend percentage with some fuel types showing increased particle number emissions, while others showed particle number reductions. In addition, the median particle diameter decreased as the blend percentage was increased. Particle and vapor phase PAHs were generally reduced with biodiesel, with the results being relatively independent of the blend percentage. The ROS concentrations increased monotonically with biodiesel blend percentage but did not exhibit strong feedstock variability. Furthermore, the ROS concentrations correlated quite well with the organic volume percentage of particles - a quantity which increased with increasing blend percentage. At higher blend percentages, the particle surface area was significantly reduced, but the particles were internally mixed with a greater organic volume percentage (containing ROS) which has implications for using surface area as a regulatory metric for diesel particulate matter (DPM) emissions. PMID- 22039913 TI - Understanding the pH-dependent behavior of graphene oxide aqueous solutions: a comparative experimental and molecular dynamics simulation study. AB - Understanding the pH-dependent behavior of graphene oxide (GO) aqueous solutions is important to the production of assembled GO or reduced GO films for electronic, optical, and biological applications. We have carried out a comparative experimental and molecular dynamics (MD) simulation study to uncover the mechanisms behind the aggregation and the surface activity of GO at different pH values. At low pH, the carboxyl groups are protonated such that the GO sheets become less hydrophilic and form aggregates. MD simulations further suggest that the aggregates exhibit a GO-water-GO sandwichlike structure and as a result are stable in water instead of precipitating. However, at high pH, the deprotonated carboxyl groups are very hydrophilic such that individual GO sheets prefer to dissolve in bulk water like a regular salt. The GO aggregates formed at low pH are found to be surface-active and do not exhibit characteristic features of surfactant micelles. Our findings suggest that GO does not behave like conventional surfactants in pH 1 and 14 aqueous solutions. The molecular-level understanding of the solution behavior of GO presented here can facilitate and improve the experimental techniques used to synthesize and sort large, uniform GO dispersions in a solution phase. PMID- 22039914 TI - Selective activation of heme oxygenase-2 by menadione. AB - While substantial progress has been made in elucidating the roles of heme oxygenases-1 (HO-1) and -2 (HO-2) in mammals, our understanding of the functions of these enzymes in health and disease is still incomplete. A significant amount of our knowledge has been garnered through the use of nonselective inhibitors of HOs, and our laboratory has recently described more selective inhibitors for HO 1. In addition, our appreciation of HO-1 has benefitted from the availability of tools for increasing its activity through enzyme induction. By comparison, there is a paucity of information about HO-2 activation, with only a few reports appearing in the literature. This communication describes our observations of the up to 30-fold increase in the in-vitro activation of HO-2 by menadione. This activation was due to an increase in Vmax and was selective, in that menadione did not increase HO-1 activity. PMID- 22039915 TI - Analysis of abstracts presented at the prosthodontic research section of IADR General Sessions 2004-2005: demographics, publication rates, and factors contributing to publication. AB - PURPOSE: The purposes of this study were to describe the demographics of abstracts presented at the prosthodontics section of IADR General Sessions from 2004 to 2005, evaluate the publication rate of abstracts, and analyze the relationship between variables in abstracts and publication. MATERIALS AND METHODS: Prosthodontics research section abstracts from the IADR General Session in 2004 and 2005 were evaluated for: number of authors, presentation type, origin, affiliation, topic, study design, statistics, study outcome, and funding. The publication rate was calculated following a PubMed search. The journal of publication, year of publication, and the length of time before publication were analyzed. Descriptive statistics were used for the data analysis; the relationships between presentation type, study design, study outcome, statistics, funding, and publication were analyzed using logistic regression (alpha= 0.05). RESULTS: From 346 abstracts, 37.0% were published. For oral presentations, 40.7% were published; 35.8% of poster presentations were published. The mean duration before publication was 26.4 months. North America had the most abstracts, and Europe had the most publications. Fixed prosthodontic research had the highest number and proportion for publication. A significant association with publication was noted for neutral study outcomes (p= 0.018), studies with funding (p= 0.035), and abstracts from Europe (p= 0.001). CONCLUSIONS: The majority of abstracts from the prosthodontics research section of IADR General Sessions from 2004 and 2005 remain unpublished. A significant association for publication was noted with neutral outcomes, funding, and abstracts from Europe. PMID- 22039916 TI - Can sputum collection practices for tuberculosis improve laboratory diagnosis of pneumonic plague in developing countries? AB - Africa reports 90% of human plague cases yet no guidelines currently exist for the safe and accurate collection of sputum from patients with suspected pneumonic plague. Using existing tuberculosis guidelines as a model and in conjunction with epidemiological and clinical features of pneumonic plague, the authors describe the importance of formal guidelines to enhance sputum collection practices and improve safety in developing countries. A model for suggested guidelines is given. PMID- 22039917 TI - Online recognition of music is influenced by relative and absolute pitch information. AB - Three experiments explored online recognition in a nonspeech domain, using a novel experimental paradigm. Adults learned to associate abstract shapes with particular melodies, and at test they identified a played melody's associated shape. To implicitly measure recognition, visual fixations to the associated shape versus a distractor shape were measured as the melody played. Degree of similarity between associated melodies was varied to assess what types of pitch information adults use in recognition. Fixation and error data suggest that adults naturally recognize music, like language, incrementally, computing matches to representations before melody offset, despite the fact that music, unlike language, provides no pressure to execute recognition rapidly. Further, adults use both absolute and relative pitch information in recognition. The implicit nature of the dependent measure should permit use with a range of populations to evaluate postulated developmental and evolutionary changes in pitch encoding. PMID- 22039918 TI - Enhanced hot-carrier cooling and ultrafast spectral diffusion in strongly coupled PbSe quantum-dot solids. AB - PbSe quantum-dot solids are of great interest for low cost and efficient photodetectors and solar cells. We have prepared PbSe quantum-dot solids with high charge carrier mobilities using layer-by-layer dip-coating with 1,2 ethanediamine as substitute capping ligands. Here we present a time and energy resolved transient absorption spectroscopy study on the kinetics of photogenerated charge carriers, focusing on 0-5 ps after photoexcitation. We compare the observed carrier kinetics to those for quantum dots in dispersion and show that the intraband carrier cooling is significantly faster in quantum-dot solids. In addition we find that carriers diffuse from higher to lower energy sites in the quantum-dot solid within several picoseconds. PMID- 22039919 TI - Protective effect of folic acid on cyclosporine-induced bone loss in rats. AB - Hyperhomocysteinemia is seen in patients with decreased bone mineral density. Cyclosporine can cause alveolar bone loss and osteopenia. It is also associated with elevated serum homocysteine levels. We aimed to investigate the effect of cyclosporine on serum homocysteine level, bone volume, and bone density, and determine whether folic acid had a protective effect against bone loss. In an experimental study, 40 male Sprague-Dawley rats were randomly assigned to five groups and received dietary supplementation for 6 weeks with olive oil (Group A), cyclosporine (Group B), folic acid (Group C), and cyclosporine plus folic acid (Group D), or no supplementation (Group F, control). Serum homocysteine, calcium, alkaline phosphatase, total bone volume, periodontal ligament volume, and volume density of bone were compared between groups. Mean serum homocysteine level (10.84 +/- 0.93 MUmol/l) was significantly higher in group B (cyclosporine supplementation) compared with the other groups (P = 0.001). Mean total mandibular volume was 46.3 +/- 13.6 mm(3) in rats treated with cyclosporine, 80.4 +/- 15.70 mm(3) in rats treated with folic acid (P = 0.004), and 73.9 +/- 21.3 mm(3) in rats treated with cyclosporine plus folic acid (P = 0.028). In our experimental model, cyclosporine increased serum homocysteine levels and decreased bone volume and density. Folic acid may have a preventive role against bone loss in rats treated with cyclosporine. PMID- 22039920 TI - Phosphorodiamidates as a promising new phosphate prodrug motif for antiviral drug discovery: application to anti-HCV agents. AB - We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterified amino acids, both d and l, and also from various simple amines. All of the compounds were evaluated versus hepatitis C virus in replicon assay, and nanomolar activity levels were observed. Many compounds were noncytotoxic at 100 MUM, leading to high antiviral selectivities. The agents are stable in acidic, neutral, and moderately basic media and in selected biological media but show efficient processing by carboxypeptidases and efficiently yield the free nucleoside monophosphate in cells. On the basis of in vitro data, eight leads were selected for additional in vivo evaluation, with the intent of selecting one candidate for progression toward clinical studies. This phosphorodiamidate prodrug method may have broad application outside of HCV and antivirals as it offers many of the advantages of phosphoramidate ProTides but without the chirality issues present in most cases. PMID- 22039921 TI - Chemical and structural status of copper associated with oxygenic and anoxygenic phototrophs and heterotrophs: possible evolutionary consequences. AB - Copper adsorption on the surface and intracellular uptake inside the cells of four representative taxons of soil and aquatic micro-organisms: aerobic rhizospheric heterotrophs (Pseudomonas aureofaciens), anoxygenic (Rhodovulum steppense) and oxygenic (cyanobacteria Gloeocapsa sp. and freshwater diatoms Navicula minima) phototrophs were studied in a wide range of pH, copper concentration, and time of exposure. Chemical status of adsorbed and assimilated Cu was investigated using in situ X-ray absorption spectroscopy. In case of adsorbed copper, XANES spectra demonstrated significant fractions of Cu(I) likely in the form of tri-coordinate complexes with O/N and/or S ligands. Upon short term reversible adsorption at all four studied micro-organisms' cell surface, Cu(II) is coordinated by 4.0 +/- 0.5 planar oxygens at an average distance of 1.97 +/- 0.02 A, which is tentatively assigned to the carboxylate groups. The atomic environment of copper incorporated into diatoms and cyanobacteria during long-term growth is similar to that of the adsorbed metal with slightly shorter distances to the first O/N neighbor (1.95 A). In contrast to the common view of Cu status in phototrophic micro-organisms, XAFS failed to detect sulfur in the nearest atomic environment of Cu assimilated by freshwater plankton (cyanobacteria) and periphyton (diatoms). The appearance of S in Cu 1st coordination shell at 2.27-2.32 A was revealed only after long-term interaction of Cu with anoxygenic phototrophs (and Cu uptake by soil heterotrophs), suggesting Cu scavenging in the form of sulfhydryl, histidine/carboxyl or a mixture of carboxylate and sulfhydryl complexes. These new structural constraints suggest that adsorbed Cu(II) is partially reduced to Cu(I) already at the cell surface, where as intracellular Cu uptake and storage occur in the form of both Cu(I)-S linked proteins and Cu(II) carboxylates. Obtained results allow to better understand how, in the course of biological evolution, micro-organisms elaborated various mechanisms of Cu uptake and storage, from passive adsorption and uptake to active, protein-controlled surface reduction, and intracellular storage. PMID- 22039922 TI - Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys. AB - BACKGROUND: Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT). The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. METHODS: Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti malarial treatment based on malaria diagnostic testing were examined. RESULTS: Most public outlets (85%) and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%), drug stores (14%), mobile providers (4%) and grocery stores (2%). Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61%) and private (42%) sectors. CONCLUSIONS: While data on the anti-malarial market shows favourable progress towards replacing artemisinin monotherapies with ACT, the widespread use of drug cocktails to treat malaria is a barrier to effective case management. Significant achievements have been made in availability of diagnostic testing and effective treatment in the public and private sectors. However, interventions to improve case management are urgently required, particularly in the private sector. Evidence-based interventions that target provider and consumer behaviour are needed to support uptake of diagnostic testing and treatment with full-course first-line anti malarials. PMID- 22039923 TI - Why are some patients admitted to psychiatric hospital while others are not? A study assessing risk during the admission interview and relationship to outcome. AB - The aim of this study was to determine what patient characteristics are used to decide whether a patient is or is not admitted to a psychiatric hospital, and what happens to those not admitted. A further aim was to determine if high levels of risk on admission predict seclusions, length of stay, or readmission within 28 days. Data were collected prospectively on consecutive presentations to an admission office via case notes and electronic databases. Eighty percent (100/127) of the adults presenting to the admission office over a typical month were admitted to hospital. Patients were more likely to be admitted if they were experiencing psychosis or exacerbation of schizophrenia, referred by other doctors or mental health teams, had a legal reason for referral, or if they were homeless. There was no association between risk for violence or suicide and seclusion rates, length of stay, or being readmitted within 28 days. It was reassuring to find that 85% of those not admitted were referred to other mental health providers, and none required admission over the following month. This study found high rates of seclusion and readmissions within 1 year, which requires further study to find strategies to reduce these rates. PMID- 22039924 TI - Comparative genomics of Helicobacter pylori and the human-derived Helicobacter bizzozeronii CIII-1 strain reveal the molecular basis of the zoonotic nature of non-pylori gastric Helicobacter infections in humans. AB - BACKGROUND: The canine Gram-negative Helicobacter bizzozeronii is one of seven species in Helicobacter heilmannii sensu lato that are detected in 0.17-2.3% of the gastric biopsies of human patients with gastric symptoms. At the present, H. bizzozeronii is the only non-pylori gastric Helicobacter sp. cultivated from human patients and is therefore a good alternative model of human gastric Helicobacter disease. We recently sequenced the genome of the H. bizzozeronii human strain CIII-1, isolated in 2008 from a 47-year old Finnish woman suffering from severe dyspeptic symptoms. In this study, we performed a detailed comparative genome analysis with H. pylori, providing new insights into non pylori Helicobacter infections and the mechanisms of transmission between the primary animal host and humans. RESULTS: H. bizzozeronii possesses all the genes necessary for its specialised life in the stomach. However, H. bizzozeronii differs from H. pylori by having a wider metabolic flexibility in terms of its energy sources and electron transport chain. Moreover, H. bizzozeronii harbours a higher number of methyl-accepting chemotaxis proteins, allowing it to respond to a wider spectrum of environmental signals. In this study, H. bizzozeronii has been shown to have high level of genome plasticity. We were able to identify a total of 43 contingency genes, 5 insertion sequences (ISs), 22 mini-IS elements, 1 genomic island and a putative prophage. Although H. bizzozeronii lacks homologues of some of the major H. pylori virulence genes, other candidate virulence factors are present. In particular, we identified a polysaccharide lyase (HBZC1_15820) as a potential new virulence factor of H. bizzozeronii. CONCLUSIONS: The comparative genome analysis performed in this study increased the knowledge of the biology of gastric Helicobacter species. In particular, we propose the hypothesis that the high metabolic versatility and the ability to react to a range of environmental signals, factors which differentiate H. bizzozeronii as well as H. felis and H. suis from H. pylori, are the molecular basis of the of the zoonotic nature of H. heilmannii sensu lato infection in humans. PMID- 22039925 TI - Grain dormancy and light quality effects on germination in the model grass Brachypodium distachyon. AB - * Lack of grain dormancy in cereal crops such as barley and wheat is a common problem affecting farming areas around the world, causing losses in yield and quality because of preharvest sprouting. Control of seed or grain dormancy has been investigated extensively using various approaches in different species, including Arabidopsis and cereals. However, the use of a monocot model plant such as Brachypodium distachyon presents opportunities for the discovery of new genes related to grain dormancy that are not present in modern commercial crops. * In this work we present an anatomical description of the Brachypodium caryopsis, and we describe the dormancy behaviour of six common diploid Brachypodium inbred genotypes. We also study the effect of light quality (blue, red and far-red) on germination, and analyse changes in abscisic acid levels and gene expression between a dormant and a non-dormant Brachypodium genotype. * Our results indicate that different genotypes display high natural variability in grain dormancy and that the characteristics of dormancy and germination are similar to those found in other cereals. * We propose that Brachypodium is an ideal model for studies of grain dormancy in grasses and can be used to identify new strategies for increasing grain dormancy in crop species. PMID- 22039926 TI - Mass spectrometry based on a coupled Cooper-pair box and nanomechanical resonator system. AB - Nanomechanical resonators (NRs) with very high frequency have a great potential for mass sensing with unprecedented sensitivity. In this study, we propose a scheme for mass sensing based on the NR capacitively coupled to a Cooper-pair box (CPB) driven by two microwave currents. The accreted mass landing on the resonator can be measured conveniently by tracking the resonance frequency shifts because of mass changes in the signal absorption spectrum. We demonstrate that frequency shifts induced by adsorption of ten 1587 bp DNA molecules can be well resolved in the absorption spectrum. Integration with the CPB enables capacitive readout of the mechanical resonance directly on the chip. PMID- 22039929 TI - Methoxy stilbenes as potent, specific, untransported, and noncytotoxic inhibitors of breast cancer resistance protein. AB - The ABCG2 multidrug transporter is known to confer cancer cell multidrug resistance by causing the efflux of anticancer drugs; therefore, selective inhibitors have the potential to improve chemotherapeutic treatments. Here, various methoxy derivatives of resveratrol are shown to be potent inhibitors of mitoxantrone efflux by ABCG2: among a series of 11 derivatives, compound 9 (3,5,3',4'-tetramethoxy trans-stilbene) had an IC(50) of 0.16 MUM and showed a maximal inhibition of 75%, as measured by flow cytometry. It was not transported, as shown by HPLC fractionation and mass spectrometry titration and the lack of any cross-resistance in cell survival experiments. Compound 9 had a very low intrinsic cytotoxicity and was able to chemosensitize the growth of resistant ABCG2-transfected HEK293 cells at submicromolar concentrations. Drug-efflux inhibition was specific for ABCG2 since very low effects were observed with ABCB1 and ABCC1. The action mechanism of compound 9 was different from that of GF120918, which produced a complete and partly competitive but not ABCG2-specific inhibition, since ABCB1 was even more strongly inhibited. The two inhibitors also displayed different effects on the ABCG2 vanadate-sensitive ATPase activity, suggesting that they either bound to distinct sites or induced different conformational changes. Mitoxantrone efflux was fully inhibited by combining low concentrations of compound 9 with either GF120918 or a transport substrate such as prazosin or nilotinib. We conclude that methoxy derivatives of stilbene are good candidates for investigating future in vivo modulation of ABCG2 drug-efflux activity. PMID- 22039930 TI - Panax ginseng, Rhodiola rosea and Schisandra chinensis. AB - Panax ginseng (Ginseng), Rhodiola rosea (Hong Jing Tian) and Schisandra chinensis (Wu Wei Zi) are well-known herbs in traditional Chinese medicine (TCM). Recently, there have been a number of studies on these three herbs. This review discusses their active components and major pharmacological effects. For P. ginseng, it has been shown to have an anti-inflammatory activity, affects pulmonary function and erectile dysfunction, improves cognition in patients with Alzheimer's disease and promotes sexual arousal in menopausal women as well as prevents cancer. For R. rosea, its effectiveness in alleviating depression and reducing fatigue is summarized in this review. Additionally, anti-cancer and other clinical effects of S. chinensis are also discussed. These three herbs are considered as adaptogens as they bear multiple functions and their effects were found to be very different in patients depending on the circumstances (age, gender, environment, diet, season, etc.). Thus, in most cases, the art of the TCM practitioner is to prescribe these herbs after a complete evaluation of overall heath status of the patients. PMID- 22039931 TI - Neurotoxin II bound to acetylcholine receptors in native membranes studied by dynamic nuclear polarization NMR. AB - Methods enabling structural studies of membrane-integrated receptor systems without the necessity of purification provide an attractive perspective in membrane protein structural and molecular biology. This has become feasible in principle since the advent of dynamic nuclear polarization (DNP) magic-angle spinning NMR spectroscopy, which delivers the required sensitivity. In this pilot study, we observed well-resolved solid-state NMR spectra of extensively (13)C labeled neurotoxin II bound to the nicotinic acetylcholine receptor (nAChR) in native membranes. We show that TOTAPOL, a biradical required for DNP, is localized at membrane and protein surfaces. The concentration of active, membrane attached biradical decreases with time, probably because of reactive components of the membrane preparation. An optimal distribution of active biradical has strong effects on the NMR data. The presence of inactive TOTAPOL in membrane proximal situations but active biradical in the surrounding water/glycerol "glass" leads to well-resolved spectra, yet a considerable enhancement (epsilon = 12) is observed. The resulting spectra of a protein ligand bound to its receptor are paving the way for further DNP investigations of proteins embedded in native membrane patches. PMID- 22039932 TI - Does a Coeliac School increase psychological well-being in women suffering from coeliac disease, living on a gluten-free diet? AB - AIM AND OBJECTIVE: To assess the effects of an active method of patient education on the psychological well-being of women with coeliac disease in remission. BACKGROUND: Despite remission with a gluten-free diet, adults with coeliac disease and especially women experience a subjective poor health. Self-management education seems to be promising tool to help patients suffering from coeliac disease to cope with their disorder. DESIGN: A randomised controlled trial. METHODS: A total of 106 women, >= 20 years, with confirmed coeliac disease, who had been on a gluten-free diet for a minimum of five years. The intervention group (n = 54) underwent a 10-session educational programme, 'Coeliac School', based on problem-based learning. The controls (n = 52) received information regarding coeliac disease sent home on a regular basis. The primary outcomes were psychological general well-being measured with a validated questionnaire. RESULTS: Participants in the Coeliac School reported a significant improvement in psychological well-being at 10 weeks, whereas the controls given usual care reported a worsening in psychological well-being. After six months, a significant improvement remained for the index of vitality. CONCLUSIONS: Patient education increased psychological well-being in women with coeliac disease. There is a need to refine the methods of patient education to make the effects of well-being more pronounced over time. RELEVANCE TO CLINICAL PRACTICE: Patient education using problem-based learning promotes self-management in coeliac disease by improving the well-being of patients who have been struggling with the gluten-free diet for years. PMID- 22039933 TI - Torsion of the abomasum in ruminants: Diagrammatic representation of rotary movements based on post-mortem findings. AB - Summary A theoretical analysis of the types of displacement of the abomasum in the abdomen is presented based on a stud of forty-seven post-mortem examinations of calves, cows, lambs and sheep showing right-sided abomasal displacement and production of knots. These displacements are quantified following the introduction of a dual-axial system. One system (XYZ) related to displacements of the abomasum on a pendulum model, the point of suspension being situated on the visceral surface of the liver and the arms consisting of parts of the digestive tract adjacent to the abomasum. The other system (x (1) y (1)z(1) ) comprises axes centered on the abomasum, about which this organ was able to rotate without changing its position in the abdomen. In order to make quantification of the displacements and deformations possible, the term twine is introduced. Twining results from interlacing of sections of the digestive tract, which are not normally adjacent. This limits the concept of torsion to helices appearing in the pyloro-duodenal region and the omaso-abomasal junction. To identify the various forms of abomasal displacement, a new terminology is introduced and basic elements suggested to make quantifications possible. PMID- 22039934 TI - Coronavirus infection in a litter of pups. AB - Summary An outbreak of a coronavirus infection in a litter of 10-week-old poodle pups from a commercial kennel is described. Coronavirus-like particles were demonstrated by electron microscopy in the intestinal contents and in the colonic mucosa. Treponemas and campylobacters were excreted in great numbers in the faeces. The gastrointestinal disturbances were complicated by hepatic and renal degeneration and severe bronchopneumonia. PMID- 22039935 TI - A seroepizootiologic study of vomiting and wasting disease virus in pigs. AB - Summary Neutralizing antibodies to Vomiting and Wasting Disease virus were found in 95 per cent of the sera collected from Belgian sows at slaughter. Piglets suckled by immune sows and kept in isolation acquired maternal antibodies; these had disappeared in all the animals at the age of 15 weeks. Most pigs had lost their maternal antibodies at the age of 11 or 12 weeks (respectively 57 per cent or 86 per cent). A serologic study on two conventional breeding farms showed that this passive immunity was replaced by active immunity between the ages of 8 and 16 weeks. No clinical disturbances appeared to be associated with the infection. The present data indicate that Vomiting and Wasting Disease virus persists on the majority of the conventional breeding farms. PMID- 22039936 TI - Nitrate poisoning in cattle. AB - Summary In a series of experiments the effect of administering KNO(2) was studied, during parturition, on the capability of oxygen transport of maternal blood and on oxygen transfer to foetal blood. The following blood parameters were analysed, MHb percentage, pO(2), O(2)-saturation, pH, pCO(2), and (NO(2)) in maternal arterial blood (carotid art.) and venous blood (jugular vein) and in foetal arterial blood (umbilical art.) and venous blood (umbilical vein). The relative O(2)-saturation was calculated from the estimated O(2)-saturation by multiplying with the factor Hb (mmol/1) minus MHb (mmol/1), divided by Hb (mmol/1). In addition, blood pressure in the carotid artery, heart rate, and respiration rate in the dam were continuously recorded for some hours. A dosage of 9 to 12 mg of NO(2)/kg body weight intravenously or of 30 mg of NO(2)/kg body weight orally to the dam caused much higher MHb percentages and NO(2) contents in the maternal blood than in the foetal blood. In maternal blood the ratio of NO(2) content td MHb percentage was proportional to that in foetal blood. In the arterial blood, MHb percentages were almost as high as in the venous blood. After administering of nitrite, relative O(2)-saturation dropped simultaneously with the increase in methaemoglobin. Nitrite treatment caused a drop in the maternal blood pressure; heart rate and respiration rate increased. O(2)-saturation in the blood in the umbilical vein was much lower in the animals with nitrite treatment than in those without. These experimental results show clearly that the oxygen capacity of the blood decreases after nitrite treatment. In pregnant cows the oxygen supply to the foetus will be adversely affected after nitrate intake, especially by the lower oxygen transfer via the placenta, though hardly at all by methaemoglobin formation in the foetal blood. When the oxygen transfer to the foetal blood decreases too sharply, intra-uterine death and ultimately abortion may result. PMID- 22039937 TI - Genuine concurrent muscular subvalvular subaortic stenosis and muscular infundibular stenosis of the right ventricle in the heart of the pig. AB - Summary Two cases of genuine concurrent muscular subvalvular aortic and muscular infundibular pulmonary stenosis in pigs are reported. The character of this morphophy-siological syndrome is discussed. The morphology of the heart of the pig predisposes this animal to the syndrome. PMID- 22039938 TI - Immunological aspects of some parasitic infections. AB - Summary In this review article, some recent developments in the immunology of parasitic infections are presented. After an introduction in which the major human parasitic infectious diseases, including malaria, african and american trypanosomiasis, leishmaniasis, filariasis an schistosomiasis are mentioned, a description of the host / parasite relationship in malaria presented. The possibility for the development of vaccins against malaria are described. The close relation between the immunological responses and the inflammatory reactions present both in Schistosoma mansoni and Trichinella spiralis infections is stressed. Particularly the recently recognized direct anti-parasitic activity of eosinophils was emphasized. Next, ways of escape of parasites from the host defence were described, with special emphasis on the immunomodulating properties of parasitic infections. Finally, the development and improvement of new immunodiagnostic methods, including the detection of circulating antigens were discussed. PMID- 22039939 TI - Egg transmission of egg drop syndrome 1976 virus in fowl. AB - Summary Egg transmission of egg drop syndrome 1976 virus (BC14 virus) in fowl was demonstrated in the second and third week after experimental infection. Eggs of BC14 virus infected hens were incubated weekly after disinfection with formaline gas. After 18 days of incubation, eggs with live embryos were homogenized. This egg material was fed to adult hens, housed in isolators. Seroconversion in these birds demonstrated egg transmission. It is suggested that egg transmission occurs as a result of viremia. PMID- 22039940 TI - The reaction of imported British Shire horses to African Horse Sickness: A case report. AB - Summary Twelve (12) heavy horses of the Shire breed imported into Nigeria in 1974 died within two months after importation. This was because of inclement weather and non-availability of AHS vaccine. PMID- 22039942 TI - Our Jungian heritage. PMID- 22039943 TI - What is The Red Book for analytical psychology? AB - The Red Book enters the field of analytical psychology belatedly, yet presents itself as a foundational text. In this paper, I try to estimate how it will affect the field and to reflect on how it can be used by contemporary readers and clinicians. Jung's own works remain the baseline for theorizing and teaching the fundamental perspectives of analytical psychology, and yet the field has grown far beyond his own contributions. Is this late inheritance of central value or only of peripheral interest for the field? It can be used in various ways and certainly shows many interesting features that link it to Jung's later works, but does it detract or does it add? And if it adds, what does it add? In The Red Book, Jung is speaking to us from the grave. What is he saying? In this paper, I explore how it can be used as an inspirational text for keeping alive the spirit of the ancestors in the field and for linking the present to the deep past. PMID- 22039944 TI - Healing the wounds of our fathers: intergenerational trauma, memory, symbolization and narrative. AB - This paper explores the history of psychoanalytical approaches to intergenerational trauma, both from the Freudian and from the Jungian schools, and addresses the need when we speak of intergenerational or transmitted trauma to better define the nature and the different categories of trauma with particular reference to extreme and cumulative traumas such as those experienced by the survivors of the Nazi death camps and the Russian gulags. Therapy with survivors and with their children requires a particular adaptation of analytical technique as what is at stake is not so much the analysis of the here and now of the transference and countertransference dynamics which indeed can in the early stages be counterproductive, but the capacity of the analyst to accept the reality of the trauma with all its devastating and mind-shattering emotions without losing the capacity to imagine and to play metaphorically with images, essential if the patient is to be able to create a space for representation. PMID- 22039945 TI - Fifteen minute stories about training. AB - This panel presentation at the Journal's conference in St Petersburg responded to the conference theme of 'Ancestors in Personal, Professional and Social History' by relating it to the experience of training and being trained on the IAAP 'router' programme in Russia. The two organizers of the programme (JW and CC) have worked in Russia for over 12 years, bringing analysts from Britain to Moscow and St Petersburg on a 'shuttle' basis as supervisors and personal analysts. A few months after handing over the router programme in December 2010 to the Russian colleagues they had trained, they invited four analysts, three Russian and one Belarusian, to tell a short personal story about their training, linking it to the theme of 'the Ancestors'. The resulting four stories are very different but complement each other, using imagery to illustrate issues concerning both value and ambivalence. JW and CC jointly wrote their story about the programme in response to the four stories, reflecting on some of their themes and from them, giving consideration to the flexibility and limits of such a model of cross cultural training. Themes in the stories included the possibility of mutual adaptation to another culture without losing tradition and identity; moving on from doctrinaire Soviet attitudes in education to embrace 'not knowing'; both organizers and routers learning from mistakes and from joint experience without guilt or shame; the need to protect reflective space amidst the constraints of time and geography. All Russian and UK contributors could finally acknowledge their shared luck to find themselves in the right place at the right time to respond to the collective revival of psychoanalytic practice in Russia. PMID- 22039946 TI - The grandfather. AB - The author, grandson of C.G. Jung, architect and historian, resident in the Kusnacht house, offers perspectives on the role of the grandfather. C.G. had a difficult relationship with his father but felt a strong rapport with his grandfather Karl Gustav Jung, even though he died before C.G.'s birth. Andreas notes that there were many parallels in the lives of the two men; C.G.'s memories and the touching personal diary left behind by Karl Gustav will be discussed. Many of Jung's other ancestors will be described from his own personal angle. The paper also encompasses C.G.'s spiritual forerunners and finally the dead, our common nameless ancestors. PMID- 22039947 TI - Jung's shadow: negation and narcissism of the Self. AB - The cave walls of prehistoric man record two contrasting hand impressions: the one positive - a direct imprint; the other negative - a blank defined by a halo of colour. Jung's disturbed, displaced contact with his mother led to a struggle in establishing an integrated sense of 'I'; instead to create a sense of Self he brilliantly contrived to illuminate the darkness around that blank impress. The resulting lifework, enhanced by Jung's multifarious capacities as artist and philosopher as well as physician, is deeply impressive; yet Winnicott (1964) in his review of Memories, Dreams, Reflections (1963) nevertheless alludes to Jung's 'own need to search for a self with which to know' (p. 450). Passages from the autobiography are considered that appear to corroborate Winnicott's contention that Jung had a 'blank', potentially psychotic, core. Yet it is also argued that the psychoanalytic mainstream has undervalued the subtlety and creativity of Jung's own intuitive response to his shadow and that a sympathetic appreciation of this can still valuably inform our contemporary approaches to narcissistic disorders, especially dissociation. PMID- 22039948 TI - Faint voices from Greenwich Village: Jung's impact on the first American avant garde. AB - In 1913 Jung made a trip to New York which was to have an important impact on the creation of modern American culture. At the invitation of Beatrice Hinkle, the first Jungian analyst in the country, he spoke to the Liberal Club, a forum for discussing progressive topics. Jung was the leading spokesman for psychoanalysis and his ideas about creative fantasy resonated with popular interest in the ideas of William James and Henri Bergson. This paper will document that visit and the influence that Hinkle had on the young people who had gravitated to Greenwich Village. She promoted Jungian psychology through her analytical practice and her translation of Jung's Wandlungen und Symbole der Libido as Psychology of the Unconscious. Her influence is evident in four key neighbourhood institutions: The Masses, a socialist magazine, The Seven Arts, an avant-garde literary magazine, the Provincetown Players theatre ensemble, and the Heterodoxy Club, America's first feminist group. Her influence is also evident at The New School where several pioneering anthropologists employed the theory of psychological types as a tool for understanding social behaviour. This paper will demonstrate that a cultural moment usually seen through a Freudian lens had, in fact, a remarkably Jungian character. PMID- 22039949 TI - Endnotes. PMID- 22039952 TI - Relationship between commuting and health outcomes in a cross-sectional population survey in southern Sweden. AB - BACKGROUND: The need for a mobile workforce inevitably means that the length of the total work day (working and traveling time) will increase, but the health effects of commuting have been surprisingly little studied apart from perceived stress and the benefits of physically active commuting. METHODS: We used data from two cross-sectional population-based public health surveys performed in 2004 and 2008 in Scania, Sweden (56% response rate). The final study population was 21, 088 persons aged 18-65, working > 30 h/week. Duration (one-way) and mode of commuting were reported. The outcomes studied were perceived poor sleep quality, everyday stress, low vitality, mental health, self-reported health, and absence from work due to sickness during the past 12 months. Covariates indicating socioeconomic status and family situation, overtime, job strain and urban/rural residency were included in multivariate analyses. Subjects walking or cycling to work < 30 min were used as a reference category. RESULTS: Monotonous relations were found between duration of public transport commuting and the health outcomes. For the category commuting > 60 min odds ratios (ORs) ranged from 1.2 - 1.6 for the different outcomes. For car commuting, the relationships were concave downward or flat, with increasing subjective health complaints up to 30-60 min (ORs ranging from 1.2 - 1.4), and lower ORs in the > 60 min category. A similar concave downward relationship was observed for sickness absence, regardless of mode of transport. CONCLUSIONS: The results of this study are concordant with the few earlier studies in the field, in that associations were found between commutation and negative health outcomes. This further demonstrates the need to consider the negative side-effects of commuting when discussing policies aimed at increasing the mobility of the workforce. Studies identifying population groups with increased susceptibility are warranted. PMID- 22039953 TI - Reexamining the boundaries of the 'normal' in ageing. AB - Textbooks and policy documents tend to present the boundary between normal and abnormal ageing as natural and clearly demarcated. In this study, we trouble the notion of natural and clearly demarcated boundaries between normal and abnormal ageing by considering how these boundaries have been established and maintained in present-day Western contexts. We draw on both Canguilhem's discussion of the normal and the abnormal and Foucault's emphasis on the role of the sociohistorical context in the social practice of boundary generation. In doing so, we critically examine common conceptualizations of normal and abnormal ageing, including those found in antiageing science, successful ageing and healthy ageing policy discourses and in health education textbooks. We argue that the growing emphasis on 'healthy' ageing both reflects and shapes the societal views of those individuals who are not able to remain disease-free and represents a kind of mystification of ageing where ageing without functional or cognitive decline is instituted as the norm. Awareness of the role that the social context plays in shaping definitions of normal and abnormal ageing encourages critical consideration of the effects that Western conceptualizations of normal ageing may have for older adults who continue to age with cognitive or functional decline. PMID- 22039954 TI - Effects of diesel particle filter retrofits and accelerated fleet turnover on drayage truck emissions at the Port of Oakland. AB - Heavy-duty diesel drayage trucks have a disproportionate impact on the air quality of communities surrounding major freight-handling facilities. In an attempt to mitigate this impact, the state of California has mandated new emission control requirements for drayage trucks accessing ports and rail yards in the state beginning in 2010. This control rule prompted an accelerated diesel particle filter (DPF) retrofit and truck replacement program at the Port of Oakland. The impact of this program was evaluated by measuring emission factor distributions for diesel trucks operating at the Port of Oakland prior to and following the implementation of the emission control rule. Emission factors for black carbon (BC) and oxides of nitrogen (NO(x)) were quantified in terms of grams of pollutant emitted per kilogram of fuel burned using a carbon balance method. Concentrations of these species along with carbon dioxide were measured in the exhaust plumes of individual diesel trucks as they drove by en route to the Port. A comparison of emissions measured before and after the implementation of the truck retrofit/replacement rule shows a 54 +/- 11% reduction in the fleet average BC emission factor, accompanied by a shift to a more highly skewed emission factor distribution. Although only particulate matter mass reductions were required in the first year of the program, a significant reduction in the fleet-average NO(x) emission factor (41 +/- 5%) was observed, most likely due to the replacement of older trucks with new ones. PMID- 22039955 TI - Effect of surface fluorination on the electrochemical and photoelectrocatalytic properties of nanoporous titanium dioxide electrodes. AB - Titanium dioxide is a widely used photocatalyst whose properties can be modified by fluoride adsorption. This work is focused on the effect of surface fluorination on the electrochemical and photoelectrocatalytic properties of TiO(2) nanoporous thin films. Surface fluorination was achieved by simple addition of HF to the working solution (pH 3.5). Open circuit potential as well as ex situ XPS measurements verify that surface modification takes place. Fluorination triggers a significant capacitance increase in the accumulation potential region, as revealed by dark voltammetric measurements for all the TiO(2) samples studied. The photoelectrocatalytic properties (measured as photocurrents under white light illumination) depend on the substrate being oxidized and, in some cases, on the nature of the TiO(2) sample. In particular, the results obtained for electrodes prepared with a mixed phase (rutile + anatase) commercial nanopowder (PI-KEM) indicate that the processes mediated by surface trapped holes, such as the photooxidation of water or methanol, are accelerated while those occurring by direct hole capture from the adsorbed state (formic acid) are retarded. The photooxidation of catechol and phenol is also enhanced upon fluorination. In such a case, the effect can be rationalized on the basis of a diminished recombination and a surface displacement of both the oxidizable organic substrates and the poisoning species formed as a result of the organics oxidation. Photoelectrochemical and in situ infrared spectroscopic measurements support these ideas. In a more general vein, the results pave the way toward a better understanding of the photocatalysis phenomena, unravelling the importance of the reactant adsorption processes. PMID- 22039956 TI - Core temperature is a greater influence than endogenous 17beta-estradiol on the exercise-induced accumulation of myocardial heat shock protein mRNA. AB - Female rats typically do not show significant increases in myocardial Hsp70 after exercise unless trained (exercise over days or weeks). 17beta-Estradiol (E2) has been linked to this inhibition, but it varies considerably over the rodent estrus cycle. Consequently, we examined whether the inhibitory effects of endogenously produced E2 (measured immediately pre-exercise) were acute in exercised female Sprague-Dawley rats (60 min treadmill running at 30 m.min(-1)). Myocardial hsp70 1 and hsp70-2 mRNA were measured 30 min post-exercise, and their expression was inversely correlated with pre-exercise plasma Epsilon2 ( hsp70-1 mRNA, r(2) = 0.308, p = 0.011; hsp70-2 mRNA, r(2) = 0.238, p = 0.029). However, hsp70-1 and hsp70-2 mRNA exhibited much stronger correlations with core temperature achieved during exercise (r(2) = 0.812, p = 0.000; and r(2) = 0.738, p = 0.000, respectively). Consequently, although endogenous Epsilon2 in gonadally intact female rats may attenuate myocardial hsp70 mRNA accumulation, suggesting a reason why training maximizes this response in females, core temperature during exercise is still a greater stimulus to this response. PMID- 22039957 TI - Calculation of relative free energies for ligand-protein binding, solvation, and conformational transitions using the GROMOS software. AB - The calculation of the relative free energies of ligand-protein binding, of solvation for different compounds, and of different conformational states of a polypeptide is of considerable interest in the design or selection of potential enzyme inhibitors. Since such processes in aqueous solution generally comprise energetic and entropic contributions from many molecular configurations, adequate sampling of the relevant parts of configurational space is required and can be achieved through molecular dynamics simulations. Various techniques to obtain converged ensemble averages and their implementation in the GROMOS software for biomolecular simulation are discussed, and examples of their application to biomolecules in aqueous solution are given. PMID- 22039958 TI - A deep rough type structure in Bordetella bronchiseptica lipopolysaccharide modulates host immune responses. AB - The present authors have previously obtained the Bordetella bronchiseptica mutant BbLP39, which contains a deep-rough lipopolysaccharide (LPS) instead the wild type smooth LPS with O antigen. This mutant was found to be altered in the expression of some proteins and in its ability to colonize mouse lungs. Particularly, in BbLP39 the expression of pertactin is decreased. To differentiate the contribution of each bacterial component to the observed phenotype, here mice defective in the LPS sensing receptor TLR4 (TLR4-defective mice) were used. In contrast to wild-type mice, infection of TLR4-defective mice with BbLP39 resulted in lung infection, which persisted for more than 10 days post-challenge. Comparative analysis of the immune responses induced by purified mutant and wild type LPSs showed that the mutant LPS induced significantly higher degrees of expression of TNF-alpha and IL-10 mRNA than did the wild type. UV matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometry analysis revealed that both LPSs had the same penta-acylated lipid A structure. However, the lipid A from BbLP39 contained pyrophosphate instead of phosphate at position 1. This structural difference, in addition to the lack of O antigen in BbLP39, may explain the functional differences between BbLP39 and wild type strains. PMID- 22039959 TI - DNA methylation status in tissues of sheep clones. AB - Genomic imprinting and DNA methylation play an important role in mammalian development. Many cloned animals showed heterogeneous DNA methylation profiles. However, there are fewer reports in cloned lambs because of a lack of genomic imprinting information. In this study, we investigated DNA methylation patterns in CpG islands and differentially methylated regions of putative imprinted gene Peg10 and imprinted genes Dlk1, Igf2R and H19 in cloned lambs. Five organs from two cloned lambs died shortly after birth and two normal controls were investigated. We observed normal DNA methylation profiles in cloned lambs. The imprinted genes Dlk1, Igf2R and H19 in livers, kidneys, hearts, muscles and lungs of the two cloned lambs exhibited relatively normal DNA methylation, except for Peg10 showing some differences between controls and cloned lambs. Our results indicate that somatic cell nuclear transfer-produced sheep exhibited relatively normal DNA methylation pattern and experienced normal DNA methylation reprogramming at imprinted loci. PMID- 22039960 TI - Practices to improve identification of adult antiretroviral therapy failure at the Lighthouse Trust clinic in Lilongwe, Malawi. AB - OBJECTIVES: Evaluating treatment failure is critical when deciding to modify antiretroviral therapy (ART). Virologic Assessment Forms (VAFs) were implemented in July 2008 as a prerequisite for ordering viral load. The form requires assessment of clinical and immunologic status. METHODS: Using the Electronic Medical Record (EMR), we retrospectively evaluated patients who met 2006 WHO guidelines for immunologic failure (>=15 years old; on ART >=6 months; CD4 count 50% drop from peak OR CD4 persistently <100 cells) at the Lighthouse Trust clinic from December 2007 to December 2009. We compared virologic screening, VAF implementation and ART modification during the same period using Fisher's exact tests and unpaired t-tests as appropriate. RESULTS: Of 7000 enrolled ART patients >=15 years old with at least two CD4 counts, 10% had immunologic failure with a median follow-up time on ART of 1.4 years (IQR: 0.8-2.3). Forty (6%) viral loads were ordered: 14 (35%) were detectable (>400 HIV RNA copies/mL) and one (7%) patient was switched to second-line therapy. Overall, 259 VAFs were completed: 67% for immunologic failure and 33% for WHO Stage 4 condition. Before VAF implementation, 1% of patients had viral loads drawn during routine care, whereas afterwards, 8% did (P<0.0001; 95% CI: 0.03-0.08). CONCLUSIONS: Clinicians did not identify a large proportion of immunologic failure patients for screening. Implementation of VAFs produced little improvement in virologic screening during routine care. Better training and monitoring systems are needed. PMID- 22039961 TI - Evaluation of 18F-labeled benzodioxine piperazine-based dopamine D4 receptor ligands: lipophilicity as a determinate of nonspecific binding. AB - Derivatization of the putative neuroleptic 1-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-4 (4-fluorobenzyl)piperazine (3a) led to a series of new dopamine receptor D4 ligands displaying high affinity (Ki=1.1-15 nM) and D2/D4 subtype selectivities of about 800-6700. These ligands were labeled with the short-lived positron emitter fluorine-18 and analyzed for their potential application for imaging studies by positron emission tomography (PET). In vitro autoradiography was used to determine their nonspecific binding behavior as a result of their structural and thus physicochemical properties. The biodistribution, in vivo stability, and brain uptake of the most promising D4 radioligand candidate were determined. This proved to be 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-4-((6-fluoropyridin-3 yl)methyl)piperazine ([18F]3d), which revealed an excellent binding pattern with a high selectivity and limited nonspecific binding in vitro. This analogue also exhibited a high stability and an extremely high brain uptake in vivo with specific binding in hippocampus, cortex, colliculus, and cerebellum as determined by ex vivo autoradiography. Thus, [18F]3d appears as a suitable D4 radioligand for in vivo imaging, encouraging continued evaluation by PET studies. PMID- 22039963 TI - The nature of transient dark states in a photoactivatable fluorescent protein. AB - Fluorescent proteins (FPs) of the green fluorescent protein family blink and bleach like all fluorophores. However, contrary to organic dyes, the mechanisms by which transient losses of fluorescence occur in FPs have received little attention. Here, we focus on the photoactivatable IrisFP, for which a transient non-fluorescent chromophoric state with distorted geometry was recently reported (Adam, V.; et al. J. Am. Chem. Soc. 009, 131, 18063). We investigated the chemical nature of this blinked state by employing quantum chemical/molecular mechanical calculations. Our findings suggest two previously unidentified dark states that display similar distorted chromophores with a transiently ruptured pi electron system. Both are protonated at atom C(alpha) of the chromophore methylene bridge. Transient protonation may occur via proton transfer from the nearby Arg66 either in the triplet state T(1) after intersystem crossing or in an anionic radical (doublet) ground state. As Arg66 is conserved in green-to-red photoconvertible FPs, these dark states are predicted to be common to all these proteins. We also suggest that C(alpha) protonated dark states may accelerate photobleaching by favoring decarboxylation of the fully conserved Glu212. PMID- 22039962 TI - Sexual recombination is a signature of a persisting malaria epidemic in Peru. AB - BACKGROUND: The aim of this study was to consider the impact that multi-clone, complex infections have on a parasite population structure in a low transmission setting. In general, complexity of infection (minimum number of clones within an infection) and the overall population level diversity is expected to be minimal in low transmission settings. Additionally, the parasite population structure is predicted to be clonal, rather than sexual due to infrequent parasite inoculation and lack of recombination between genetically distinct clones. However, in this low transmission of the Peruvian Amazon, complex infections are becoming more frequent, in spite of decreasing infection prevalence. In this study, it was hypothesized that sexual recombination between distinct clonal lineages of Plasmodium falciparum parasites were altering the subpopulation structure and effectively maintaining the population-level diversity. METHODS: Fourteen microsatellite markers were chosen to describe the genetic diversity in 313 naturally occurring P. falciparum infections from Peruvian Amazon. The population and subpopulation structure was characterized by measuring: clusteredness, expected heterozygosity (He), allelic richness, private allelic richness, and linkage disequilibrium. Next, microsatellite haplotypes and alleles were correlated with P. falciparum merozoite surface protein 1 Block 2 (Pfmsp1-B2) to examine the presence of recombinant microsatellite haplotypes. RESULTS: The parasite population structure consists of six genetically diverse subpopulations of clones, called "clusters". Clusters 1, 3, 4, and 6 have unique haplotypes that exceed 70% of the total number of clones within each cluster, while Clusters 2 and 5 have a lower proportion of unique haplotypes, but still exceed 46%. By measuring the He, allelic richness, and private allelic richness within each of the six subpopulations, relatively low levels of genetic diversity within each subpopulation (except Cluster 4) are observed. This indicated that the number of alleles, and not the combination of alleles, are limited. Next, the standard index of association (IAS) was measured, which revealed a significant decay in linkage disequilibrium (LD) associated with Cluster 6, which is indicative of independent assortment of alleles. This decay in LD is a signature of this subpopulation approaching linkage equilibrium by undergoing sexual recombination. To trace possible recombination events, the two most frequent microsatellite haplotypes observed over time (defined by either a K1 or Mad20) were selected as the progenitors and then potential recombinants were identified in within the natural population. CONCLUSIONS: Contrary to conventional low transmission models, this study provides evidence of a parasite population structure that is superficially defined by a clonal backbone. Sexual recombination does occur and even arguably is responsible for maintaining the substructure of this population. PMID- 22039964 TI - Direct condensation of sulfonamide and formamide: NaI-catalyzed synthesis of N sulfonyl formamidine using TBHP as oxidant. AB - A new N-sulfonyl formamidine synthesis was developed via NaI-catalyzed direct condensation of sulfonamide and formamide. The green methodology is featured by high atom economy, easily available starting materials, the lack of need for a transition-metal catalyst, no requirement of hazardous reagent, operational simplicity, and good tolerance with diverse functional groups. Mechanistic studies suggest that the protocol proceeds based upon in situ generated TsN.NaI. PMID- 22039965 TI - Polyamidoamine (PAMAM) dendrimer conjugate specifically activates the A3 adenosine receptor to improve post-ischemic/reperfusion function in isolated mouse hearts. AB - BACKGROUND: When stimulated by small molecular agonists, the A3 adenosine receptor (AR) mediates cardioprotective effects without inducing detrimental hemodynamic side effects. We have examined pharmacologically the protective properties of a multivalent dendrimeric conjugate of a nucleoside as a selective multivalent agonist for the mouse A3AR. RESULTS: A PAMAM dendrimer fully substituted by click chemistry on its peripheral groups with 64 moieties of a nucleoside agonist was shown to be potent and selective in binding to the mouse A3AR and effective in cardioprotection in an isolated mouse heart model of ischemia/reperfusion (I/R) injury. This conjugate MRS5246 and a structurally related model compound MRS5233 displayed binding Ki values of 0.04 and 3.94 nM, respectively, and were potent in in vitro functional assays to inhibit cAMP production. A methanocarba (bicyclo[3.1.0]hexane) ring system in place of ribose maintained a North conformation that is preferred at the A3AR. These analogues also contained a triazole linker along with 5'-N-methyl-carboxamido and 2-alkynyl substitution, previously shown to be associated with species-independent A3AR selectivity. Both MRS5233 and MRS5246 (1 and 10 nM) were effective at increasing functional recovery of isolated mouse hearts after 20 min ischemia followed by 45 min reperfusion. A statistically significant greater improvement in the left ventricular developed pressure (LVDP) by MRS5246 compared to MRS5233 occurred when the hearts were observed throughout reperfusion. Unliganded PAMAM dendrimer alone did not have any effect on functional recovery of isolated perfused mouse hearts. 10 nM MRS5246 did not improve functional recovery after I/R in hearts from A3AR gene "knock-out" (A3KO) mice compared to control, indicating the effects of MRS5246 were A3AR-specific. CONCLUSIONS: Covalent conjugation to a versatile drug carrier enhanced the functional potency and selectivity at the mouse A3AR and maintained the cardioprotective properties. Thus, this large molecular weight conjugate is not prevented from extravasation through the coronary microvasculature. PMID- 22039966 TI - A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania. AB - BACKGROUND: Children with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately. METHODS: 255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin. RESULTS: There was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n=22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI=0.12, 1.10; p=0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p<0.01). HIV infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n=48; 2 cm, compared to 1 cm in the placebo group; 95% CI=0.20, 1.70; p=0.01; p for interaction by age group=0.01). CONCLUSIONS: Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure. CLINICALTRIALS.GOV IDENTIFIER: NCT00145184. PMID- 22039967 TI - Resolving the contributions of the membrane-bound and periplasmic nitrate reductase systems to nitric oxide and nitrous oxide production in Salmonella enterica serovar Typhimurium. AB - The production of cytotoxic nitric oxide (NO) and conversion into the neuropharmacological agent and potent greenhouse gas nitrous oxide (N2O) is linked with anoxic nitrate catabolism by Salmonella enterica serovar Typhimurium. Salmonella can synthesize two types of nitrate reductase: a membrane-bound form (Nar) and a periplasmic form (Nap). Nitrate catabolism was studied under nitrate rich and nitrate-limited conditions in chemostat cultures following transition from oxic to anoxic conditions. Intracellular NO production was reported qualitatively by assessing transcription of the NO-regulated genes encoding flavohaemoglobin (Hmp), flavorubredoxin (NorV) and hybrid cluster protein (Hcp). A more quantitative analysis of the extent of NO formation was gained by measuring production of N2O, the end-product of anoxic NO-detoxification. Under nitrate-rich conditions, the nar, nap, hmp, norV and hcp genes were all induced following transition from the oxic to anoxic state, and 20% of nitrate consumed in steady-state was released as N2O when nitrite had accumulated to millimolar levels. The kinetics of nitrate consumption, nitrite accumulation and N2O production were similar to those of wild-type in nitrate-sufficient cultures of a nap mutant. In contrast, in a narG mutant, the steady-state rate of N2O production was ~30-fold lower than that of the wild-type. Under nitrate-limited conditions, nap, but not nar, was up-regulated following transition from oxic to anoxic metabolism and very little N2O production was observed. Thus a combination of nitrate-sufficiency, nitrite accumulation and an active Nar-type nitrate reductase leads to NO and thence N2O production, and this can account for up to 20% of the nitrate catabolized. PMID- 22039968 TI - Fires enhance flammability in Ulex parviflorus. PMID- 22039969 TI - Drug-eluting Ti wires with titania nanotube arrays for bone fixation and reduced bone infection. AB - Current bone fixation technology which uses stainless steel wires known as Kirschner wires for fracture fixing often causes infection and reduced skeletal load resulting in implant failure. Creating new wires with drug-eluting properties to locally deliver drugs is an appealing approach to address some of these problems. This study presents the use of titanium [Ti] wires with titania nanotube [TNT] arrays formed with a drug delivery capability to design alternative bone fixation tools for orthopaedic applications. A titania layer with an array of nanotube structures was synthesised on the surface of a Ti wire by electrochemical anodisation and loaded with antibiotic (gentamicin) used as a model of bone anti-bacterial drug. Successful fabrication of TNT structures with pore diameters of approximately 170 nm and length of 70 MUm is demonstrated for the first time in the form of wires. The drug release characteristics of TNT-Ti wires were evaluated, showing a two-phase release, with a burst release (37%) and a slow release with zero-order kinetics over 11 days. These results confirmed our system's ability to be applied as a drug-eluting tool for orthopaedic applications. The established biocompatibility of TNT structures, closer modulus of elasticity to natural bones and possible inclusion of desired drugs, proteins or growth factors make this system a promising alternative to replace conventional bone implants to prevent bone infection and to be used for targeted treatment of bone cancer, osteomyelitis and other orthopaedic diseases. PMID- 22039970 TI - Structural characterization of inhibitors with selectivity against members of a homologous enzyme family. AB - The aspartate biosynthetic pathway provides essential metabolites for many important biological functions, including the production of four essential amino acids. As this critical pathway is only present in plants and microbes, any disruptions will be fatal to these organisms. An early pathway enzyme, l aspartate-beta-semialdehyde dehydrogenase, produces a key intermediate at the first branch point of this pathway. Developing potent and selective inhibitors against several orthologs in the l-aspartate-beta-semialdehyde dehydrogenase family can serve as lead compounds for antibiotic development. Kinetic studies of two small molecule fragment libraries have identified inhibitors that show good selectivity against l-aspartate-beta-semialdehyde dehydrogenases from two different bacterial species, Streptococcus pneumoniae and Vibrio cholerae, despite the presence of an identical constellation of active site amino acids in this homologous enzyme family. Structural characterization of enzyme-inhibitor complexes have elucidated different modes of binding between these structurally related enzymes. This information provides the basis for a structure-guided approach to the development of more potent and more selective inhibitors. PMID- 22039971 TI - Anxiety sensitivity and anxiety as correlates of expected, experienced and recalled labor pain. AB - There has been a good deal of research on the role of anxiety sensitivity in pain perception, but only recently have investigators begun to assess its role in labor pain. The aim of this study was to investigate the nature of this relationship as well as the relationship of state and trait anxiety with labor pain. Assessments of maximum and average labor pain were completed in three different time periods (before, during and immediately after labor, and 1 month postpartum). Anxiety and anxiety sensitivity measures were completed during the late stage of pregnancy. A total of 46 primiparous healthy pregnant women, carrying a single child, participated in the study. State anxiety correlated significantly with maximum (r?=?0.352, p?100-fold selectivity against PI3K/AKT-pathway kinases. The cellular potency of these analogues was assessed by the inhibition of AKT phosphorylation (T308) and by their antiproliferation activity against a number of tumor cell lines. PMID- 22040024 TI - Differential proteolysis of sigma regulators controls cell-surface signalling in Pseudomonas aeruginosa. AB - Cell-surface signalling systems are widespread in Gram-negative bacteria. In these systems gene expression occurs following binding of a ligand, commonly a siderophore, to a receptor protein in the outer membrane. The receptor interacts with a sigma regulator protein that extends from the periplasm into the cytoplasm to control the activity of a cognate sigma factor. The mechanisms of signal transduction in cell-surface signalling systems have not been determined. Here we investigate signal transduction in the pyoverdine, ferrichrome and desferrioxamine siderophore systems of Pseudomonas aeruginosa. When pyoverdine is present the sigma regulator FpvR undergoes complete proteolysis resulting in activation of two sigma factors PvdS and FpvI and expression of genes for pyoverdine synthesis and uptake. When pyoverdine is absent subfragments of FpvR inhibit PvdS and FpvI. Similarly, subfragments of the sigma regulators FoxR and FiuR are formed in the absence of desferrioxamine and ferrichrome. These are much less abundant when the siderophores are present and downstream gene expression takes place. In all three systems RseP (MucP/YaeL) is required for complete proteolysis of the sigma regulator and sigma factor activity. These findings indicate that regulated proteolysis is a general mechanism for signal transduction in cell-surface signalling. PMID- 22040022 TI - Pulmonary adenocarcinoma: a renewed entity in 2011. AB - Lung cancer, of which non-small-cell lung cancer comprises the majority, is the leading cause of cancer-related deaths in the United States and worldwide. Lung adenocarcinomas are a major subtype of non-small-cell lung cancers, are increasing in incidence globally in both males and females and in smokers and non smokers, and are the cause for almost 50% of deaths attributable to lung cancer. Lung adenocarcinoma is a tumour with complex biology that we have recently started to understand with the advent of various histological, transcriptomic, genomic and proteomic technologies. However, the histological and molecular pathogenesis of this malignancy is still largely unknown. This review will describe advances in the molecular pathology of lung adenocarcinoma with emphasis on genomics and DNA alterations of this disease. Moreover, the review will discuss recognized lung adenocarcinoma preneoplastic lesions and current concepts of the early pathogenesis and progression of the disease. We will also portray the field cancerization phenomenon and lineage-specific oncogene expression pattern in lung cancer and how both remerging concepts can be exploited to increase our understanding of lung adenocarcinoma pathogenesis for subsequent development of biomarkers for early detection of adenocarcinomas and possibly personalized prevention. PMID- 22040026 TI - Enhanced photo-sensitivity through an increased light-trapping on Si by surface nano-structuring using MWCNT etch mask. AB - We demonstrate an enhanced photo-sensitivity (PS) through an increased light trapping using surface nano-structuring technique by inductively coupled plasma (ICP) etching on multi-walled carbon nanotube (MWCNT) etch masked Si with hexamethyl-disilazane (HMDS) dispersion. In order for a systematic comparison, four samples are prepared, respectively, by conventional photolithography and ICP etching using MWCNT as a etch mask. MWCNT-etched Si with HMDS dispersion shows the highest RMS roughness and the lowest reflectance of the four. Two test device structures are fabricated with active regions of bare-Si as a reference and MWCNT etch masked Si with HMDS dispersion. The increased light-trapping was most significant at mid-UV, somewhat less at visible and less noticeable at infrared. With an ICP-etched Si using CNT HMDS dispersion, PS is very sharply increased. This result can lead to applications in optoelectronics where the enhancement in light-trapping is important. PMID- 22040027 TI - Functional studies of CYP21A2 mutants complement structural and clinical predictions of disease severity in CAH. PMID- 22040025 TI - Evaluation of diverse alpha/beta-backbone patterns for functional alpha-helix mimicry: analogues of the Bim BH3 domain. AB - Peptidic oligomers that contain both alpha- and beta-amino acid residues, in regular patterns throughout the backbone, are emerging as structural mimics of alpha-helix-forming conventional peptides (composed exclusively of alpha-amino acid residues). Here we describe a comprehensive evaluation of diverse alpha/beta peptide homologues of the Bim BH3 domain in terms of their ability to bind to the BH3-recognition sites on two partner proteins, Bcl-x(L) and Mcl-1. These proteins are members of the anti-apoptotic Bcl-2 family, and both bind tightly to the Bim BH3 domain itself. All alpha/beta-peptide homologues retain the side-chain sequence of the Bim BH3 domain, but each homologue contains periodic alpha residue -> beta(3)-residue substitutions. Previous work has shown that the alphaalphabetaalphaalphaalphabeta pattern, which aligns the beta(3)-residues in a 'stripe' along one side of the helix, can support functional alpha-helix mimicry, and the results reported here strengthen this conclusion. The present study provides the first evaluation of functional mimicry by alphaalphabeta and alphaalphaalphabeta patterns, which cause the beta(3)-residues to spiral around the helix periphery. We find that the alphaalphaalphabeta pattern can support effective mimicry of the Bim BH3 domain, as manifested by the crystal structure of an alpha/beta-peptide bound to Bcl-x(L), affinity for a variety of Bcl-2 family proteins, and induction of apoptotic signaling in mouse embryonic fibroblast extracts. The best alphaalphaalphabeta homologue shows substantial protection from proteolytic degradation relative to the Bim BH3 alpha-peptide. PMID- 22040028 TI - Satellite cell pool enhancement in rat plantaris muscle by endurance training depends on intensity rather than duration. AB - AIM: Increases in the number of satellite cells are necessary for the maintenance of normal muscle function. Endurance training enhances the satellite cell pool. However, it remains unclear whether exercise intensity or exercise duration is more important to enhance the satellite cell pool. This study examined the effects of different intensity and duration of endurance training on the satellite cell pool in rat skeletal muscle. METHODS: Forty-one 17-week-old female Sprague-Dawley rats were assigned to control (n = 8), high intensity and high duration (n = 7), high intensity and low duration (n = 8), low intensity and high duration (n = 9) and low intensity and low duration (n = 9) groups. Training groups exercised 5 days per week on a motor driven treadmill for 10 weeks. After the training period, animals were anaesthetized and the plantaris muscles were removed, weighed and analysed for immunohistochemical and histochemical properties. RESULTS: Although no significant differences were found in muscle mass, mean fibre area and myonuclei per muscle fibre between all groups, the percentage of satellite cells was significantly higher in the high-intensity groups than in the other groups (P < 0.05). CONCLUSION: Increases in the satellite cell pool of skeletal muscle following endurance training depend on the intensity rather than duration of exercise. PMID- 22040029 TI - Retrospective chart review of catatonia in child and adolescent psychiatric patients. AB - OBJECTIVE: Identify the frequency of catatonia among at-risk children and adolescents receiving psychiatric treatment. METHOD: Subjects were children and adolescents (<18 years), who had received psychiatric treatment at a University Hospital during 2004-2009, and were diagnosed with disorders with known risk for catatonia or displayed symptoms suggestive of catatonia. Approval was obtained from the Investigational Review Board (IRB). The first 101 (n = 101) subjects were selected among 570 subjects identified by psychiatric diagnoses: any pervasive developmental disorder, psychosis-NOS (Not Otherwise Specified), intermittent explosive disorder, mental retardation, catatonia and neuroleptic malignant syndrome. Subjects met study-defined criteria for catatonia, if they had three or more of the following symptoms: unexplained agitation/excitement, disturbed or unusual movements, reduced movements, repetitive or stereotyped movements, or reduced or loss of speech. RESULTS: Eighteen (17.8%) subjects, among a group suspected to be at a higher risk for catatonia, met the study defined criteria for this syndrome. However, only two subjects had been diagnosed by their treatment providers. Higher rates of intellectual disability and aggression were found among the group that met study-criteria. CONCLUSION: We concluded that catatonia is under recognized and undertreated among children and adolescents receiving psychiatric treatment. PMID- 22040030 TI - Discrepancies between survey and administrative data on the use of mental health services in the general population: findings from a study conducted in Quebec. AB - BACKGROUND: Population surveys and health services registers are the main source of data for the management of public health. Yet, the validity of survey data on the use of mental health services has been questioned repeatedly due to the sensitive nature of mental illness and to the risk of recall bias. The main objectives of this study were to compare data on the use of mental health services from a large scale population survey and a national health services register and to identify the factors associated with the discrepancies observed between these two sources of data. METHODS: This study was based on the individual linkage of data from the cycle 1.2 of the Canadian Community Health Survey (CCHS-1.2) and from the health services register of the Regie de l'assurance maladie du Quebec (RAMQ). The RAMQ is the governmental agency managing the Quebec national health insurance program. The analyses mostly focused on the 637 Quebecer respondents who were recorded as users of mental health services in the RAMQ and who were self-reported users or non users of these services in the CCHS-1.2. RESULTS: Roughly 75%, of those recorded as users of mental health services users in the RAMQ's register did not report using mental health services in the CCHS-1.2. The odds of disagreement between survey and administrative data were higher in seniors, individuals with a lower level of education, legal or de facto spouses and mothers of young children. They were lower in individuals with a psychiatric disorder and in frequent and more recent users of mental health services according to the RAMQ's register. CONCLUSIONS: These findings support the hypotheses that social desirability and recall bias are likely to affect the self-reported use of mental health services in a population survey. They stress the need to refine the investigation of mental health services in population surveys and to combine survey and administrative data, whenever possible, to obtain an optimal estimation of the population need for mental health care. PMID- 22040032 TI - Metabolic effects of intra-abdominal fat in GHRKO mice. AB - Mice with targeted deletion of the growth hormone receptor (GHRKO mice) are growth hormone (GH) resistant, small, obese, hypoinsulinemic, highly insulin sensitive and remarkably long-lived. To elucidate the unexpected coexistence of adiposity with improved insulin sensitivity and extended longevity, we examined effects of surgical removal of visceral (epididymal and perinephric) fat on metabolic traits related to insulin signaling and longevity. Comparison of results obtained in GHRKO mice and in normal animals from the same strain revealed disparate effects of visceral fat removal (VFR) on insulin and glucose tolerance, adiponectin levels, accumulation of ectopic fat, phosphorylation of insulin signaling intermediates, body temperature, and respiratory quotient (RQ). Overall, VFR produced the expected improvements in insulin sensitivity and reduced body temperature and RQ in normal mice and had opposite effects in GHRKO mice. Some of the examined parameters were altered by VFR in opposite directions in GHRKO and normal mice, and others were affected in only one genotype or exhibited significant genotype * treatment interactions. Functional differences between visceral fat of GHRKO and normal mice were confirmed by measurements of adipokine secretion, lipolysis, and expression of genes related to fat metabolism. We conclude that in the absence of GH signaling, the secretory activity of visceral fat is profoundly altered and unexpectedly promotes enhanced insulin sensitivity. The apparent beneficial effects of visceral fat in GHRKO mice may also explain why reducing adiposity by calorie restriction fails to improve insulin signaling or further extend longevity in these animals. PMID- 22040033 TI - Total synthesis of hirsutellone B via Ullmann-type direct 13-membered macrocyclization. AB - Total synthesis of Hirsutellone B has been achieved by a convergent synthetic strategy. This synthesis features direct construction of the highly strained 13 membered macrocycle of Hirsutellone B utilizing the Ullmann-type reaction. To the best of our knowledge, this is the first application of macrocyclization utilizing an intramolecular Ullmann-type reaction between an aliphatic alcohol and aryl halide. PMID- 22040034 TI - Perinatal immunoproteins predict the risk of cerebral palsy in preterm children. AB - OBJECTIVE: To investigate whether blood cytokines during the perinatal period predict the risk of cerebral palsy (CP) in preterm infants. METHODS: This prospective cohort study comprised 169 children born before 32 weeks of gestation. Cord blood was drawn at birth, and 109 cytokines were analyzed using microarrays. Eleven cytokines were further measured from both cord and peripheral blood on days 1 and 7. Cerebral palsy was confirmed at 5 years of age. RESULTS: Cerebral palsy was diagnosed in 19 children. Five clusters of cord blood cytokines were scored using factor analysis. According to logistic regression analysis, the scores of factors 1 and 2 independently predicted the risk of CP. These cytokines included several growth factors and chemokines, and they all tended to be higher in children with CP than in children without CP. Inflammatory cytokine levels were associated with CP risk on days 1 and 7 after birth. CONCLUSION: The high blood concentrations of various cytokines during the perinatal period may relate to CP, and these cytokines may influence the pathways leading to early insult in the central nervous system. The risk profile of inflammatory cytokines is different at birth than during the first week after birth. PMID- 22040035 TI - An optimized relaxation-based coherence transfer NMR experiment for the measurement of side-chain order in methyl-protonated, highly deuterated proteins. AB - Relaxation violated coherence transfer NMR spectroscopy has emerged as a powerful experimental tool for the quantitative measurement of amplitudes of motion of methyl containing side-chains. Typically, the experiments, performed on proteins that are highly deuterated and methyl-protonated, monitor the build-up of methyl (1)H double-quantum magnetization. Because all three protons in a methyl group are degenerate, such coherences can only result from differential relaxation of transverse magnetization components, which in turn reflect the extent and time scale of motion of the methyl probe [Tugarinov, V., Sprangers, R.; Kay, L.E. J. Am. Chem. Soc. 2007, 129, 1743-1750]. We show here that a 50% gain in the sensitivity of the experiment can be achieved through selection of (1)H triple quantum coherence, thereby significantly increasing the utility of the approach. A theoretical treatment rationalizes the sensitivity gain that is subsequently verified through experiment. The utility of the methodology is demonstrated on a number of proteins, including the 360 kDa alpha(7)alpha(7) "half-proteasome". PMID- 22040037 TI - Cyclic di-GMP, an established secondary messenger still speeding up. AB - The secondary messenger cyclic di-GMP coordinately regulates the transition between motility/sessility/virulence in bacterial populations and upon adaptation to novel habitats. Thereby, multiple independent regulatory circuits regulate a diversity of targets. This specific output response is surprising considering the diverse physiological processes regulated by this signalling molecule, which range from transcription to proteolysis and clearly demonstrates the presence of sophisticated developmental programmes in these so-called simple organisms. PMID- 22040036 TI - Estrogenicity of outer scales of onion on uteri of immature mice. AB - We aimed to investigate the estrogen-like activities of the outer scales of onion and garlic on the uteri of immature mice. This work compared the estrogenic effects induced by estradiol with the effects of plant extract (onion, garlic) in models of immature mice (n = 72). The animals were divided into 6 groups, with 12 animals in each group, as follows: Group I (control group), Group II (estradiol treated group), Group III (onion extract treated group), Group IV (onion extract treated group after blockage of estrogen receptors), Group V (garlic extract treated group), and Group VI (garlic extract treated group after blockage of estrogen receptors). Uterine wet weight/body mass ratios were determined. Uterotrophic bioassay, immunohistochemical assay for estrogen receptor and proliferative marker Ki67, uterine contractility, and serum estrogen levels were investigated. Onion extract induced proliferative changes in the uterus, it also increased the uterine mass and epithelial cell height. Also, the frequency and amplitude of myometrial contractility were significantly increased in the group treated with onion extract. This estrogenic activity could be attributed to the quercetin and daidzein content, and activation of estrogenic receptors, as these effects disappeared after blockage of E2 receptors. Our results support the possible estrogenic properties of the onion extract, which could be attributed to quercetin and daidzein, but not that of garlic extract. PMID- 22040038 TI - Application of XPS and solution chemistry analyses to investigate soluble manganese removal by MnO(x)(s)-coated media. AB - X-ray photoelectron spectroscopy (XPS) was applied to investigate Mn(II) removal by MnO(x)(s)-coated media under experimental conditions similar to the engineered environment of drinking water treatment plants in the absence and presence of chlorine. Macroscopic and spectroscopic results suggest that Mn(II) removal at pH 6.3 and pH 7.2 in the absence of chlorine was mainly due to adsorption onto the MnO(x)(s) surface coating, while removal in the presence of chlorine was due to a combination of initial surface adsorption followed by subsequent surface catalyzed oxidation. However, Mn(III) was identified by XPS analyses of the Mn 3p photoline for experiments performed in the absence of chlorine at pH 6.3 and pH 7.2, suggesting that surface-catalyzed Mn oxidation also occurred at these conditions. Results obtained at pH 8.2 at 8 and 0.5 mg.L(-1) dissolved oxygen in the absence of chlorine suggest that Mn(II) removal was mainly due to initial adsorption followed by surface-catalyzed oxidation. XPS analyses suggest that Mn(IV) was the predominant species in experiments operated in the presence of chlorine. This study confirms that the use of chlorine combined with the catalytic action of MnO(x)(s) oxides is effective for Mn(II) removal from drinking water filtration systems. PMID- 22040039 TI - General practitioners' experience and benefits from patient evaluations. AB - BACKGROUND: It has now for many years been recognised that patient evaluations should be undertaken as an integral part of the complex task of improving the quality of general practice care. Yet little is known about the general practitioners' (GPs') benefit from patient evaluations. Aim 1 was to study the impact on the GPs of a patient evaluation and subsequent feedback of results presented at a plenary session comprising a study guide for the results and group discussions. Aim 2 was to study possible facilitators and barriers to the implementations of the results raised by the patient evaluation process. METHODS: A patient evaluation survey of 597 voluntarily participating GPs was performed by means of the EUROPEP questionnaire. Evaluation results were fed back to the GPs as written reports at a single feedback meeting with group discussions of the results. Between 3 and 17 months after the feedback, the 597 GPs received a questionnaire with items addressing their experience with and perceived benefit from the evaluations. RESULTS: 79.4% of the GPs responded. 33% of the responding GPs reported that the patient evaluation had raised their attention to the patient perspective on the quality of general practice care. Job satisfaction had improved among 26%, and 21% had developed a more positive attitude to patient evaluations. 77% of the GPs reported having learnt from the evaluation. 54% had made changes to improve practice, 82% would recommend a patient evaluation to a colleague and 75% would do another patient evaluation if invited. 14% of the GPs had become less positive towards patient evaluations, and job satisfaction had decreased among 3%. CONCLUSIONS: We found a significant impact on the GPs regarding satisfaction with the process and attitude towards patient evaluations, GPs' attention to the patients' perspective on care quality and their job satisfaction. Being benchmarked against the average seemed to raise barriers to the concept of patient evaluations and difficulties interpreting the results may have formed a barrier to their implementation which was partly overcome by adding qualitative data to the quantitative results. The GPs' significant willingness to share and discuss the results with others may have served as a facilitator. PMID- 22040040 TI - Letter to the editor--Increasing body weight of motorcycle riders. PMID- 22040041 TI - Commentary on: Kremer C, Racette S, Dionne CA, Sauvageau A. Discrimination of falls and blows in blunt head trauma: systematic study of the hat brim rule in relation to skull fractures. J Forensic Sci 2008 May; 53(3):716-9. PMID- 22040043 TI - Commentary on: Horvath F, Palmatier JJ. Critique of Horvath-Palmatier Laboratory study on effectiveness of exclusive v. non-exclusive control questions in polygraph examination. J Forensic Sci 2008;53(4):889-99. PMID- 22040045 TI - Author's response: My response to Dr. Dawes et al.'s letter follows (owing to the U.S. Air Force Research Laboratory's approval process required of authors, the response could not be submitted to the Journal of Forensic Sciences in a timely manner. PMID- 22040046 TI - Carbon nanotube wiring: a tool for straightforward electrochemical biosensing at magnetic particles. AB - Here, we combine the unique properties of carbon nanotubes (CNTs) and magnetic particles (MPs) to develop a novel biosensing approach for the specific detection of electroactive labels and targets. The assay is based on label/target capture and concentration using MPs. It follows addition of CNTs, which adsorb onto the surface of the beads. The subsequent magnetic entrapment of the CNT/MP complexes onto an electrode allows straightforward electrochemical sensing of the MP surface by exploiting CNT wiring. As a proof of concept, the assay has been applied to detection of ferrocene labels, and to the specific immunodetection of dopamine in both artificial saline solutions and real sample matrixes. The results demonstrate the applicability of CNT as wiring tools for enzymeless and substrateless electrochemical biosensing. PMID- 22040047 TI - Anti-inflammatory properties of intestinal Bifidobacterium strains isolated from healthy infants. AB - Certain Bifidobacterium strains have been shown to inhibit inflammatory responses in intestinal epithelial cells. However, the precise mechanisms of these effects, including the chemical nature of the active compounds, remain to be elucidated. Here partial characterization of the anti-inflammatory properties of Bifidobacterium strains isolated from feces of healthy infants is reported. It was found that conditioned media (CM) of all strains studied are capable of attenuating tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide- (LPS) induced inflammatory responses in the HT-29 cell line. In contrast, neither killed bifidobacterial cells, nor cell-free extracts showed such activities. Further investigations resulted in attribution of this activity to heat-stable, non-lipophilic compound(s) resistant to protease and nuclease treatments and of molecular weight less than 3 kDa. The anti-inflammatory effects were dose- and time-dependent and associated with inhibition of IkappaB phosphorylation and nuclear factor-kappa light chain enhancer of activated B cells (NF-kappaB) dependent promoter activation. The combined treatments of cells with CMs and either LPS or TNF-alpha, but not with CMs alone, resulted in upregulation of transforming growth factor-beta1, IkappaBzeta, and p21(CIP) mRNAs. Our data suggest certain species-specificities of the anti-inflammatory properties of bifidobacteria. This observation should prompt additional validation studies using larger set of strains and employing the tools of comparative genomics. PMID- 22040049 TI - Impact of obesity on respiratory function. AB - Obesity has long been recognized as having significant effects on respiratory function. The topic has been studied for at least the last half century, and some clear patterns have emerged. Obese patients tend to have higher respiratory rates and lower tidal volumes. Total respiratory system compliance is reduced for a variety of reasons, which will be discussed. Lung volumes tend to be decreased, especially expiratory reserve volume. Spirometry, gas exchange and airway resistance all tend to be relatively well preserved when adjusted for lung volumes. Patients may be mildly hypoxaemic, possibly due to ventilation-perfusion mismatching at the base of the lungs, where microatelectasis is likely to occur. Weight loss leads to a reversal of these changes. For all of these changes, the distribution of fat, that is, upper versus lower body, may be more important than body mass index. PMID- 22040048 TI - An amino-terminal signal peptide of Vfr protein negatively influences RopB dependent SpeB expression and attenuates virulence in Streptococcus pyogenes. AB - Streptococcal pyrogenic exotoxin B (SpeB) is an extracellular cysteine protease that is a critical virulence factor made by the major human pathogen group A Streptococcus (GAS). speB expression is dependent on the regulator of proteinase B (RopB) and is upregulated with increasing cell density and during infection. Because computer modelling suggested significant structural similarity between RopB and peptide-sensing regulatory proteins made by other Gram-positive bacteria, we hypothesized that speB expression is influenced by RopB-peptide interactions. Inactivation of the gene (vfr) encoding the virulence factor related (Vfr) protein resulted in increased speB transcript level during the exponential growth phase, whereas provision of only the amino-terminal region of Vfr comprising the secretion signal sequence in trans restored a wild-type speB expression profile. Addition of the culture supernatant from a Vfr signal peptide expressing GAS strain restored wild-type speB transcript level to a vfr inactivated isogenic mutant strain. A distinct peptide in the Vfr secretion signal sequence specifically bound to recombinant RopB. Finally, overexpression of the Vfr secretion signal sequence significantly decreased speB transcript level and attenuated GAS virulence in two mouse models of invasive infection. Taken together, these data delineate a previously unknown small peptide-mediated regulatory system that controls GAS virulence factor production. PMID- 22040051 TI - Correction. PMID- 22040050 TI - HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a cancer targeting gene-viro-therapy strategy. AB - BACKGROUND: In previously published studies, oncolytic adenovirus-mediated gene therapy has produced good results in targeting cancer cells. However, safety and efficacy, the two most important aspects in cancer therapy, remain serious challenges. The specific expression or deletion of replication related genes in an adenovirus has been frequently utilized to regulate the cancer cell specificity of a virus. Accordingly, in this study, we deleted 24 bp in E1A (bp924-bp947) and the entirety of E1B, including those genes encoding E1B 55kDa and E1B19kDa. We used the survivin promoter (SP) to control E1A in order to construct a new adenovirus vector named Ad.SP.E1A(Delta24).DeltaE1B (briefly Ad.SPDD). HCCS1 (hepatocellular carcinoma suppressor 1) is a novel tumor suppressor gene that is able to specifically induce apoptosis in cancer cells. The expression cassette AFP-HCCS1-WPRE-SV40 was inserted into Ad.SPDD to form Ad.SPDD-HCCS1, enabling us to improve the safety and efficacy of oncolytic mediated gene therapy for liver cancer. RESULTS: Ad.SPDD showed a decreased viral yield and less toxicity in normal cells but enhanced toxicity in liver cancer cells, compared with the cancer-specific adenovirus ZD55 (E1B55K deletion). Ad.SPDD-HCCS1 exhibited a potent anti-liver-cancer ability and decreased toxicity in vitro. Ad.SPDD-HCCS1 also showed a measurable capacity to inhibit Huh-7 xenograft tumor growth on nude mice. The underlying mechanism of Ad.SPDD-HCCS1 induced liver cancer cell death was found to be via the mitochondrial apoptosis pathway. CONCLUSIONS: These results demonstrate that Ad.SPDD-HCCS1 was able to elicit reduced toxicity and enhanced efficacy both in vitro and in vivo compared to a previously constructed oncolytic adenovirus. Ad.SPDD-HCCS1 could be a promising candidate for liver cancer therapy. PMID- 22040053 TI - Alkaloids from the Chinese vine Gnetum montanum. AB - During a high-throughput screening campaign of a prefractionated natural product library, fractions from the Chinese vine Gnetum montanum showed in vitro activity against Pseudomonas aeruginosa wild-type strain, PAO1. UV-directed isolation of the organic extract from the vine leaves resulted in the purification of the new natural products N-methyllaudanosolinium trifluoroacetate (1), 3'-hydroxy-N,N dimethylcoclaurinium trifluoroacetate (2), 1,9,10-trihydroxy-2-methoxy-6 methylaporphinium trifluoroacetate (3), and 6a,7-didehydro-1,9,10-trihydroxy-2 methoxy-6-methylaporphinium trifluoroacetate (4). Compound 4 is described here for the first time, and this is the first report of compounds 1-3 as natural products. Compounds 1-3 were found to racemize over time. Starting from commercially available (+)-boldine, through a series of semisynthetic reactions, a mechanism for the racemization of the isolated compounds is proposed. The known natural products (-)-latifolian A (5) and magnocurarine (6) were also isolated during these studies. The antibacterial activity was explained by the presence of 5, which displayed an IC50 value of 9.8 MUM (MIC = 35 MUM). PMID- 22040054 TI - Accurate sperm morphology assessment predicts sperm function. AB - Sperm morphology has been associated with in vitro as well as in vivo fertilisation. The study aimed to evaluate the possible relation between the percentage of spermatozoa with normal morphology and the following sperm functional assays: (i) zona-induced acrosome reaction (ZIAR); (ii) DNA integrity; (iii) chromatin condensation; (iv) sperm apoptosis; and (v) fertilisation rates. Regression analysis was employed to calculate the association between morphology and different functional tests. Normal sperm morphology correlated significantly with the percentages of live acrosome-reacted spermatozoa in the ZIAR (r = 0.518; P < 0.0001; n = 92), DNA integrity (r = -0.515; P = 0.0018; n = 34), CMA(3) positive spermatozoa (r = -0.745; P < 0.0001; n = 92), sperm apoptosis (r = 0.395; P = 0.0206; n = 34) and necrosis (r = -0.545; P = 0.0009; n = 34). Negative correlations existed between for the acrosome reaction, and DNA integrity, while negative associations were recorded with the percentages of CMA(3) -positive spermatozoa, apoptotic and necrotic spermatozoa. Sperm morphology is related to sperm dysfunction such as poor chromatin condensation, acrosome reaction and DNA integrity. Negative and significant correlations existed between normal sperm morphology and chromatin condensation, the percentage of spermatozoa with abnormal DNA and spermatozoa with apoptotic activity. The authors do not regard sperm morphology as the only test for the diagnosis of male fertility, but sperm morphology can serve as a valuable indicator of underlying dysfunction. PMID- 22040055 TI - Development of robust organosilica membranes for reverse osmosis. AB - Hybrid organically bridged silica membranes have attracted considerable attention because of their high performances in a variety of applications. Development of robust reverse osmosis (RO) membranes to withstand aggressive operating conditions is still a major challenge. Here, a new type of microporous organosilica membrane has been developed and applied in reverse osmosis. Sol-gel derived organosilica RO membranes reject isopropanol with rejection higher than 95%, demonstrating superior molecular sieving ability for neutral solutes of low molecular weight. Due to the introduction of an inherently stable hybrid network structure, the membrane withstands higher temperatures in comparison with commercial polyamide RO membranes, and is resistant to water to at least 90 degrees C with no obvious changes in filtration performance. Furthermore, both an accelerated chlorine-resistance test and Fourier transform infrared analysis confirm excellent chlorine stability in this material, which demonstrates promise for a new generation of chlorine-resistant RO membrane materials. PMID- 22040056 TI - Degradable self-assembling dendrons for gene delivery: experimental and theoretical insights into the barriers to cellular uptake. AB - This paper uses a combined experimental and theoretical approach to gain unique insight into gene delivery. We report the synthesis and investigation of a new family of second-generation dendrons with four triamine surface ligands capable of binding to DNA, degradable aliphatic-ester dendritic scaffolds, and hydrophobic units at their focal points. Dendron self-assembly significantly enhances DNA binding as monitored by a range of experimental methods and confirmed by multiscale modeling. Cellular uptake studies indicate that some of these dendrons are highly effective at transporting DNA into cells (ca. 10 times better than poly(ethyleneimine), PEI). However, levels of transgene expression are relatively low (ca. 10% of PEI). This indicates that these dendrons cannot navigate all of the intracellular barriers to gene delivery. The addition of chloroquine indicates that endosomal escape is not the limiting factor in this case, and it is shown, both experimentally and theoretically, that gene delivery can be correlated with the ability of the dendron assemblies to release DNA. Mass spectrometric assays demonstrate that the dendrons, as intended, do degrade under biologically relevant conditions over a period of hours. Multiscale modeling of degraded dendron structures suggests that complete dendron degradation would be required for DNA release. Importantly, in the presence of the lower pH associated with endosomes, or when bound to DNA, complete degradation of these dendrons becomes ineffective on the transfection time scale-we propose this explains the poor transfection performance of these dendrons. As such, this paper demonstrates that taking this kind of multidisciplinary approach can yield a fundamental insight into the way in which dendrons can navigate barriers to cellular uptake. Lessons learned from this work will inform future dendron design for enhanced gene delivery. PMID- 22040057 TI - Combinatorial screening of highly active Pd binary catalysts for electrochemical oxygen reduction. AB - Electro-catalysts omitting platinum are of interest to reduce the cost of fuel cells. The development of non-Pt alloys for this purpose would require a large number of experiments. Palladium-based bimetallic electro-catalysts using eight different metals were computationally evaluated for the oxygen reduction reaction (ORR) and were made and tested in acidic media using combinatorial methods. A Pd Co alloy showed the closest oxygen adsorption energy to platinum in simple theoretical model calculations, suggesting the highest ORR activity. This prediction was confirmed experimentally, suggesting that the single parameter of oxygen adsorption energy can be a useful guide to developing non-Pt oxygen reduction catalysts in the future. PMID- 22040058 TI - Position Statement of the Chinese Diabetes Society regarding stem cell therapy for diabetes. PMID- 22040059 TI - STEM nanoanalysis of Au/Pt/Ti-Si3N4 interfacial defects and reactions during local stress of SiGe HBTs. AB - A new insight on the behavior of metal contact-insulating interfaces in SiGe heterojunction bipolar transistor is given by high-performance aberration corrected scanning transmission electron microscopy (STEM) analysis tools equipped with sub-nanometric probe size. It is demonstrated that the presence of initial defects introduced during technological processes play a major role in the acceleration of degradation mechanisms of the structure during stress. A combination of energy-filtered transmission electron microscopy analysis with high angle annular dark field STEM and energy dispersive spectroscopy provides strong evidence that migration of Au-Pt from the metal contacts to Ti/Si3N4 interface is one of the precursors to species interdiffusion and reactions. High current densities and related local heating effects induce the evolution of the pure Ti initial layer into mixture layer composed of Ti, O, and N. Local contamination of Ti layers by fluorine atoms is also pointed out, as well as rupture of TiN thin barrier layer. PMID- 22040060 TI - Involvement of bystander effect in suppression of the cytokine production induced by heavy-ion broad beams. AB - PURPOSE: Immune cells accumulate in and around cancers and cooperate with each other using specific cytokines to attack the cancer cells. The heavy-ion beams for cancer therapy may stimulate immune cells and affect on the immune system. However, it is still poorly understood how the immune cells are stimulated by ion beams. Here, we irradiated immune cells using heavy-ion beams and analyzed changes in production of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) that are important cytokine for the cancer treatment. MATERIALS AND METHODS: The human THP-1 monocytes were differentiated into macrophages and then irradiated using carbon-ion broad-beams (108 keV MUm(-1)). To examine the bystander response after heavy-ion irradiation, a very small fraction (approx. 0.45%) of the cell population was irradiated using heavy-ion microbeams. After irradiation, we examined the cytokine productions. RESULTS: When cells were irradiated with 5 Gy, cytokine levels were reduced after both microbeam irradiation and broad-beam irradiation. TNF-alpha production of macrophages with the nitric oxide (NO) inhibitor-treatment increased after carbon-ion broad-beam. NO was involved in the radiation-induced suppression of TNF-alpha production. CONCLUSIONS: The suppression of cytokine production arose after irradiation with heavy-ions, and may also be induced in the surrounding non-irradiated cells via the bystander effect. PMID- 22040061 TI - Long-term follow-up of patients with portal vein thrombosis and myeloproliferative neoplasms. AB - BACKGROUND: Myeloproliferative neoplasms (MPNs) are frequently identified as an underlying cause in patients with non-cirrhotic portal vein thrombosis (PVT). The aim of this study was to describe the long-term outcome of patients with PVT and MPN. METHODS: A cohort study was performed including all adult patients referred to our hospital between 1980 and 2008 with non-cirrhotic, non-malignant PVT and confirmed MPN. RESULTS: A total of 44 patients (70% female) were included, with a median age at PVT-diagnosis of 48 years (range 18-79). In 31 patients (70%) PVT was the first manifestation of an MPN. Additional risk factors for thrombosis were present in 20 patients (45%). Median follow-up was 5.8 years (range 0.4-21). Twenty-three patients (52%) were treated with oral anticoagulants after diagnosis of PVT, of whom 15 (34%) received long-term therapy. During follow-up, 17 patients (39%) experienced at least one episode of gastrointestinal bleeding. Additional thrombotic events occurred in 12 patients (27%). Twelve patients (27%) had progression of the underlying MPN. Seventeen patients (39%) died at a median age of 64 years (range 30-88). Death was directly related to end-stage MPN in eight patients (47%) and to a new thrombotic event in three patients (18%). No patients died from gastrointestinal bleeding. CONCLUSIONS: PVT is often the presenting symptom of an underlying MPN, highlighting the need for thorough screening for this disease. Recurrent thrombosis is a common and severe complication in patients with PVT and MPN. Mortality is primarily related to the underlying MPN and not to complications of portal hypertension. PMID- 22040062 TI - Michael Ernest Nesheim (February 5, 1945 - June 4, 2011). PMID- 22040063 TI - Synthesis of biaryls via AlCl3 catalyzed domino reaction involving cyclization, dehydration, and oxidation. AB - A new chemical access has been developed to synthesize biaryls from substituted acetophenones, phenylacetones, dihydrochalcone, and 2-acetylnaphthalene in reasonably good yields at room temperature via a domino reaction sequence of AlCl(3) catalyzed cyclization, dehydration, and then oxidation. PMID- 22040064 TI - Frequencies of SLC44A2 alleles encoding human neutrophil antigen-3 variants in the African American population. AB - BACKGROUND: The human neutrophil antigen-3 (HNA-3) epitopes reside on the choline transporter-like protein-2 (CTL2). A single-nucleotide substitution (461G>A; Arg154Gln) on the CTL2 gene (SLC44A2) defines the allele SLC44A2*1, which expresses HNA-3a, and SLC44A2*2, which expresses HNA-3b; an additional substitution (457C>T; Leu153Phe) in SLC44A2*1:2 may impact genotyping systems. People who only express HNA-3b may develop anti-HNA-3a. These alloantibodies have been linked to severe transfusion-related acute lung injury, which may be a reason to screen blood donors for SLC44A2*2 homozygosity. For Caucasian and Asian populations, SLC44A2 allele frequencies are known. Our primary objective was to determine the SLC44A2 allele frequencies in the African American population. STUDY DESIGN AND METHODS: Purified DNA from 334 individuals (202 male, 132 female; 241 African American, 93 Caucasian) was collected. Two real-time polymerase chain reaction assays were developed to genotype all samples; results were confirmed by nucleotide sequencing. RESULTS: In 241 African American donors, the allele frequency of SLC44A2*1 was 93% (85%-<100%; 95% confidence intervals, Poisson distribution) while SLC44A2*2 was 7% (5%-10%). In 93 Caucasian donors, the allele frequency of SLC44A2*1 was 83% (71%-98%) and SLC44A2*2 was 17% (11% 24%), matching previously reported data for Caucasians but differing from African Americans (p < 0.001, Fisher's exact test). CONCLUSIONS: This study describes the allele frequencies of the three known HNA-3 variants in an African American population. We found that African Americans have a significantly lower probability of possessing the SLC44A2*2 allele and may thus be less likely to form the clinically relevant anti-HNA-3a. PMID- 22040065 TI - Borrowing strength with nonexchangeable priors over subpopulations. AB - We introduce a nonparametric Bayesian model for a phase II clinical trial with patients presenting different subtypes of the disease under study. The objective is to estimate the success probability of an experimental therapy for each subtype. We consider the case when small sample sizes require extensive borrowing of information across subtypes, but the subtypes are not a priori exchangeable. The lack of a priori exchangeability hinders the straightforward use of traditional hierarchical models to implement borrowing of strength across disease subtypes. We introduce instead a random partition model for the set of disease subtypes. This is a variation of the product partition model that allows us to model a nonexchangeable prior structure. Like a hierarchical model, the proposed clustering approach considers all observations, across all disease subtypes, to estimate individual success probabilities. But in contrast to standard hierarchical models, the model considers disease subtypes a priori nonexchangeable. This implies that when assessing the success probability for a particular type our model borrows more information from the outcome of the patients sharing the same prognosis than from the others. Our data arise from a phase II clinical trial of patients with sarcoma, a rare type of cancer affecting connective or supportive tissues and soft tissue (e.g., cartilage and fat). Each patient presents one subtype of the disease and subtypes are grouped by good, intermediate, and poor prognosis. The prior model should respect the varying prognosis across disease subtypes. The practical motivation for the proposed approach is that the number of accrued patients within each disease subtype is small. Thus it is not possible to carry out a clinical study of possible new therapies for rare conditions, because it would be impossible to plan for sufficiently large sample size to achieve the desired power. We carry out a simulation study to compare the proposed model with a model that assumes similar success probabilities for all subtypes with the same prognosis, i.e., a fixed partition of subtypes by prognosis. When the assumption is satisfied the two models perform comparably. But the proposed model outperforms the competing model when the assumption is incorrect. PMID- 22040066 TI - Interventions to improve work outcomes in work-related PTSD: a systematic review. AB - BACKGROUND: Posttraumatic stress disorder acquired at work can be debilitating both for workers and their employers. The disorder can result in increased sick leave, reduced productivity, and even unemployment. Furthermore, workers are especially unlikely to return to their previous place of employment after a traumatic incident at work because of the traumatic memories and symptoms of avoidance that typically accompany the disorder. Therefore, intervening in work related PTSD becomes especially important in order to get workers back to the workplace. METHODS: A systematic literature search was conducted using Medline, PsycINFO, Embase, and Web of Science. The articles were independently screened based on inclusion and exclusion criteria, followed by a quality assessment of all included articles. RESULTS: The systematic search identified seven articles for inclusion in the review. These consisted of six research articles and one systematic review. The review focused specifically on interventions using real exposure techniques for anxiety disorders in the workplace. In the research articles addressed in the current review, study populations included police officers, public transportation workers, and employees injured at work. The studies examined the effectiveness of EMDR, cognitive-behavioural techniques, and an integrative therapy approach called brief eclectic psychotherapy. Interestingly, 2 of the 6 research articles addressed add-on treatments for workplace PTSD, which were designed to treat workers with PTSD who failed to respond to traditional evidence-based psychotherapy. CONCLUSIONS: Results of the current review suggest that work-related interventions show promise as effective strategies for promoting return to work in employees who acquired PTSD in the workplace. Further research is needed in this area to determine how different occupational groups with specific types of traumatic exposure might respond differently to work-tailored treatments. PMID- 22040067 TI - A false sense of security? The U.S. Food and Drug Administration's framework for evaluating new supplement ingredients. AB - The evidence sufficient to establish the expectation of safety for new ingredients in dietary supplements is an area of considerable controversy. Recently, the U.S. Food and Drug Administration (FDA) proposed a sound scientific framework for evaluating the safety of new ingredients. The level of evidence the FDA requires (i.e., in vitro, animal or human testing) hinges on three key factors: (1) documented history of use; (2) the dose and formulation of the new ingredient compared with the historically used ingredient; and (3) the supplement's recommended use (i.e., daily or as needed). Despite its strengths, the framework requires four key modifications to ensure the expectation of safety: (1) historical use should rarely, if ever, be sufficient to replace experimental data; (2) entirely novel ingredients should undergo, at a minimum, a 90-day human testing; (3) manufacturers should be required to submit to the FDA all available data regarding new ingredients, both favorable and unfavorable; and (4) before assuming that consumers follow instructions on supplement labels, this assumption should be empirically confirmed. In the absence of significant modifications, the FDA's guidance may have the effect of providing a false sense of security to consumers seeking safe dietary supplements. PMID- 22040068 TI - Complete mitochondrial genome of the Hodgson's bat Myotis formosus (Mammalia, Chiroptera, Vespertilionidae). AB - The first complete mitochondrial genome (17,159 bp) of the Hodgson's bat Myotis formosus, which is an endangered species in South Korea, was sequenced and characterized. The genome included 13 protein-coding, 22 tRNA, and 2 rRNA genes, and 1 control region. It has high AT content and the same gene arrangement pattern as those of typical vertebrate mitochondrial genome. Within the control region, a 80 bp tandem repeat unit was iterated five times which was found in Domain I. It has been observed only in the vespertilionid bat group, and could contribute to identifying the species or genus, and also distinguishing it from other bat families. PMID- 22040069 TI - Complete mitochondrial genome of the Baikal teal Anas formosa (Aves, Anseriformes, Anatidae). AB - The Baikal teal Anas formosa (Aves, Anseriformes, Anatidae) is classified as "Vulnerable" on the IUCN Red List. Here, whole mitochondrial genome of A. formosa was amplified and sequenced. The total length of the Baikal teal mitochondrial genome is 16,594 bp, which consists of 13 protein-coding, 2 rRNA, 22 tRNA genes and 1 control region. The characteristics of the mitochondrial genomes were analyzed and discussed in detail. PMID- 22040070 TI - Complete mitochondrial genome of the black-headed snake Sibynophis collaris (Squamata, Serpentes, Colubridae). AB - The black-headed snake Sibynophis collaris (Reptilia, Squamata, Colubridae) is a least concern species in the world. Two universal and two specific polymerase chain reaction (PCR) primers were used for long PCRs to amplify the whole mitochondrial genome of S. collaris. The products were subjected to do sequencing reactions. The complete genome is 17,163 bp in size, containing 37 genes coding for 13 proteins, 2 rRNAs, 22 tRNAs, and 2 control regions (CRI and CRII). The results could play an important role in the preservation of genetic resources for helping conservation of the endangered species. PMID- 22040071 TI - Complete mitochondrial genome sequence of the Korean water deer Hydropotes inermis argyropus (Cervidae, Capreolinae). AB - The complete mitochondrial genome sequence of Hydropotes inermis argyropus consists of 13 protein-coding, 22 tRNA, and two rRNA genes, and 1 control region (CR). Three overlaps among the 13 protein-coding genes were found: ATP8/ATP6, ND4L/ND4, and ND5/ND6. The CR was located between the tRNA-Pro and tRNA-Phe genes and is 928 bp in length. The typical conserved domains, such as TAS and CSB, were identified in the CR. PMID- 22040072 TI - Complete mitochondrial genome of the nerippe fritillary butterfly, Argynnis nerippe (Lepidoptera: Nymphalidae). AB - The complete mitochondrial genome sequence of the nerippe fritillary butterfly, Argynnis nerippe, which is listed as an endangered species in Korea, is described with an emphasis on the A+T-rich region. The 15,140-bp long circular molecule consisted of 13 protein-coding genes, two rRNA genes, 22 tRNA genes and 1 control region, known in insect as the A+T-rich region, as found in typical metazoans. The 329-bp long A+T-rich region located between srRNA and tRNA(Met) possessed the highest A/T content (95.7%) than any other region of the genome. Along with the several conserved sequences found typically in the lepidopteran insects the genome contained one tRNA(Met)-like and tRNA(Leu)(UUR)-like sequence in the A+T rich region. PMID- 22040073 TI - The complete mitochondrial genome sequence of the Amur leopard cat, Prionailurus bengalensis euptilurus. AB - The total length of the Prionailurus bengalensis euptilurus genome is 16,990 bp, with a total base composition of 33% A, 27.4% T, 26% C, and 13.5% G. The base compositions present clearly the A-T skew, which is most obvious in the tRNA genes (64%). PMID- 22040074 TI - The complete mitochondrial genome of human parasitic roundworm, Ascaris lumbricoides. AB - The genome length of the Ascaris lumbricoides, human parasitic roundworm, is 14,281 bp with a nucleotide composition of 22.1% A, 49.8% T, 7.8% C, and 20.3% G. The genome consists of 12 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 1 control region. PMID- 22040075 TI - The complete mitochondrial genome of the Japanese mud shrimp Upogebia major (Crustacea, Decapoda). AB - We determined a full-length sequence of mitochondrial (mt) genome from Upogebia major. This is the first complete mt genome report for infraorder Thalassinidea in Decapoda, Crustacea. Our result showed that U. major generally followed a typical pancrustacean gene order but some tRNA genes showed a very unique gene arrangement such as duplication or translocation. Since none of the complete mt genome sequences in the infraorder Thalassinidea are available yet, this report will provide additional information in relation to mt genome diversity and evolution of the decapods. PMID- 22040076 TI - The complete mitochondrial genome of the Korean field mouse Apodemus peninsulae (Rodentia, Murinae) from Korea. AB - We have determined the complete mitochondrial genome of a subspecies of the Korean field mouse, Apodemus peninsulae peninsulae, from South Korea. The total length of the A. p. peninsulae genome is 16,268 bp with a base composition of 34.5% A, 30.7% T, 22.6% C, and 12.2% G. PMID- 22040078 TI - The complete mitochondrial genome of the greater horseshoe bat subspecies, Rhinolophus ferrumequinum korai (Chiroptera: Rhinolophidae). AB - The total length of the mitogenome of Rhinolophus ferrumequinum korai is 16,839 bp with a total base composition of 31.8% A, 25.4% T, 28.7% C, and 14.0% G. The mitogenome consists of 13 protein-coding genes, 2 rRNA (12S and 16S RNA) genes, 22 tRNA genes, and 1 control region. PMID- 22040077 TI - The mitochondrial genome of Apodemus peninsulae (Rodentia, Muridae). AB - The complete mitochondrial (mt) genome of the Korean field mouse Apodemus peninsulae was sequenced and found to be 16,266 bp in length. The mt protein coding genes of A. peninsulae had ATG, GTG, ATC, and ATA as initiation codons and TAA, TAG, TA, and T as termination codons. Two forms each of trnL and trnS and the three tRNA clusters, IQM, WANCY, and HSL were identified, as in the typical Rodentia mt genome. Among tRNAs, abnormal cloverleaf structure of trnS((AGY)) was identified in DHU arm. The l-strand replication origin has the potential to form a stable stem-loop structure and control region has several conserved sequence elements. PMID- 22040079 TI - Analysis of the mitochondrial haplogroups of farm and wild-living raccoon dogs in Poland. AB - Raccoon dogs' mitochondrial DNA genes (MT-CYTB, MT-CO1 and MT-CO2) containing a total of 1.5 kbp exhibited 11 synonymous substitutions in the polymorphism described, with almost 73% found in the gene MT-CO2. The polymorphism was observed in 27.3% of the loci in wild-living animals, and in over 90% of the loci in farm raccoon dogs. Seven mitochondrial haplogroups have been determined, among which three (Np1, Np2 and Np4) were found in the wild-living raccoon dogs and the other four (Np3, Np5, Np6 and Np7) in the farm animals. The occurrence of new haplogroups in the farm animals indicates the appearance of adaptive mutations. Differences were observed between the sequence under study and the reference sequence in MT-CYTB; they involved two non-synonymous substitutions (T304I and F332L). Analyses carried out to determine the deleterious effect of mutations indicated an almost 50% probability that a single amino acid substitution (T304I) in the protein has a negative impact on its function. PMID- 22040080 TI - The complete mitochondrial genome of the taimen, Hucho taimen, and its unusual features in the control region. AB - The whole mitochondrial genome of Hucho taimen was firstly sequenced and characterized. The genome is 16,833 bp in length and contains 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a noncoding control region. Twelve protein-coding genes on the heavy strand showed that the content of A+T was higher than that of G+C, whereas the nd6 protein-coding gene on the light strand displayed an opposite pattern. We described the secondary structure of the origin of light strand (oriL) replication and found that the conserved 5'-GCCGG-3' sequence motif is variable in H. taimen and some other salmonids. We conclude that the control region is variable in length and represents the high A+T content, compared with other mitochondrial control regions available in Salmonidae and other non-salmonids. Additionally, another interesting feature of H. taimen mitogenome is that a T-type mononucleotide microsatellite and an 82 bp tandem repeat were identified in the control region. PMID- 22040081 TI - The complete mitogenome of the snakehead Channa argus (Perciformes: Channoidei): genome characterization and phylogenetic implications. AB - To better understand the phylogenetic status of the snakehead, Channa argus, we determined its complete mitogenome sequence using long-polymerase chain reaction and the direct sequencing method. The complete mitogenome sequence was 16,559 bp in length and contained 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 1 control region (D-loop), the gene composition/order of which was identical to that observed in most other vertebrates. This was the first report of the mitogenome sequence in suborder Channoidei. Phylogenetic relationships of 14 perciform suborders based on mitogenome sequences were reconstructed using Bayesian inference and maximum likelihood methods. The results strongly supported the monophyly of Perciformes and the snakehead, as a representative species of suborder Channoidei, formed the most basal branch having sister relationship with the clade containing all other analyzed perciform fishes. The further phylogenetic analyses of six channid species, based on cytochrome b gene, suggested that two channid genera constituted reciprocally monophyletic clades. In addition, the relaxed molecular clock method was used to estimate divergence dates among major suborders of Perciformes and major species in Channoidei. PMID- 22040082 TI - DNA barcoding of fishes of Laguna de Bay, Philippines. AB - Laguna de Bay, the largest lake in the Philippines, is an important part of the country's fisheries industry. It is also home to a number of endemic fishes including Gobiopterus lacustris (Herre 1927) of family Gobiidae, Leiopotherapon plumbeus (Kner 1864) of family Terapontidae, Zenarchopterus philippinus (Peters 1868) of family Hemiramphidae and Arius manillensis Valenciennes 1840 of family Ariidae. Over the years, a steady decline has been observed in the abundance and diversity of native fishes in the lake due to anthropogenic disturbances. In this study, a total of 71 specimens of 18 different species belonging to 18 genera, 16 families, and seven orders were DNA barcoded using the mitochondrial cytochrome c oxidase subunit I (COI) gene. All of the fish species were discriminated by their COI sequences and one endemic species G. lacustris, showing deep genetic divergence, was highlighted for further taxonomic investigation. Average Kimura 2 parameter genetic distances within species, family, and order were 1.33%, 18.91%, and 24.22%, respectively. These values show that COI divergence increases as taxa become less exclusive. All of the COI sequences obtained were grouped together according to their species designation in the Neighbor-joining tree that was constructed. This study demonstrated that DNA barcoding has great potential as a tool for fast and accurate species identification and also for highlighting species that warrant further taxonomic investigation. PMID- 22040083 TI - Fixed-dose single tablet combinations: an alternative for initial therapy of patients with type 2 diabetes? PMID- 22040084 TI - Stability of foam films of oppositely charged polyelectrolyte/surfactant mixtures: effect of isoelectric point. AB - In the present paper, the influence of the surfactant concentration and the degree of charge of a polymer on foam film properties of oppositely charged polyelectrolyte/surfactant mixtures has been investigated. To verify the assumption that the position of the isoelectric point (IEP) does not change the character of the foam film stabilities, the position of the IEP of the polyelectrolyte/surfactant mixtures has been shifted in two different ways. Within the first series of experiments, the foam film properties were studied using a fixed surfactant concentration of 3 * 10(-5) M in the mixture. Due to the low surfactant concentration, this is a rather dilute system. In the second approach, a copolymer of nonionic and ionic monomer units was used to lower the charge density of the polymer. This gave rise to additional interactions between the polyelectrolyte and the surfactant, which makes the description of the foam film behavior more complex. In both systems, the same characteristics of the foam film stabilities were found: The foam film stability is reduced toward the IEP of the system, followed by a destabilization around the IEP. At polyelectrolyte concentrations above the IEP, foam films are very stable. However, the concentration range where unstable films were formed was rather broad, and the mechanisms leading to the destabilization had different origins. The results were compared with former findings on PAMPS/C(14)TAB mixtures with an IEP of 10(-4) M. PMID- 22040085 TI - Synthesis and hydride transfer reactions of cobalt and nickel hydride complexes to BX3 compounds. AB - Hydrides of numerous transition metal complexes can be generated by the heterolytic cleavage of H(2) gas such that they offer alternatives to using main group hydrides in the regeneration of ammonia borane, a compound that has been intensely studied for hydrogen storage applications. Previously, we reported that HRh(dmpe)(2) (dmpe = 1,2-bis(dimethylphosphinoethane)) was capable of reducing a variety of BX(3) compounds having a hydride affinity (HA) greater than or equal to the HA of BEt(3). This study examines the reactivity of less expensive cobalt and nickel hydride complexes, HCo(dmpe)(2) and [HNi(dmpe)(2)](+), to form B-H bonds. The hydride donor abilities (DeltaG(H(-)) degrees ) of HCo(dmpe)(2) and [HNi(dmpe)(2)](+) were positioned on a previously established scale in acetonitrile that is cross-referenced with calculated HAs of BX(3) compounds. The collective data guided our selection of BX(3) compounds to investigate and aided our analysis of factors that determine favorability of hydride transfer. HCo(dmpe)(2) was observed to transfer H(-) to BX(3) compounds with X = H, OC(6)F(5), and SPh. The reaction with B(SPh)(3) is accompanied by the formation of dmpe-(BH(3))(2) and dmpe-(BH(2)(SPh))(2) products that follow from a reduction of multiple B-SPh bonds and a loss of dmpe ligands from cobalt. Reactions between HCo(dmpe)(2) and B(SPh)(3) in the presence of triethylamine result in the formation of Et(3)N-BH(2)SPh and Et(3)N-BH(3) with no loss of a dmpe ligand. Reactions of the cationic complex [HNi(dmpe)(2)](+) with B(SPh)(3) under analogous conditions give Et(3)N-BH(2)SPh as the final product along with the nickel-thiolate complex [Ni(dmpe)(2)(SPh)](+). The synthesis and characterization of HCo(dedpe)(2) (dedpe = Et(2)PCH(2)CH(2)PPh(2)) from H(2) and a base is also discussed, including the formation of an uncommon trans dihydride species, trans [(H)(2)Co(dedpe)(2)][BF(4)]. PMID- 22040086 TI - The Crp regulator of Pseudomonas putida: evidence of an unusually high affinity for its physiological effector, cAMP. AB - Although the genome of Pseudomonas putida KT2440 encodes an orthologue of the crp gene of Escherichia coli (encoding the cAMP receptor protein), the regulatory scope of this factor seems to be predominantly co-opted in this bacterium for controlling non-metabolic functions. In order to investigate the reasons for such a functional divergence in otherwise nearly identical proteins, the Crp regulator of P. putida (Crp(P. putida)) was purified to apparent homogeneity and subject to a battery of in vitro assays aimed at determining its principal physicochemical properties. Analytical ultracentrifugation indicated effector-free Crp(P. putida) to be a dimer in solution that undergoes a significant change in its hydrodynamic shape in the presence of cAMP. Such a conformational transition was confirmed by limited proteolysis of the protein in the absence or presence of the inducer. Thermodynamic parameters calculated by isothermal titration calorimetry revealed a tight cAMP-Crp(P. putida) association with an apparent K(D) of 22.5 +/- 2.8 nM, i.e. much greater affinity than that reported for the E. coli's counterpart. The regulator also bound cGMP, but with a K(D) = 2.6 +/- 0.3 uM. An in vitro transcription system was then set up with purified P. putida's RNA polymerase for examining the preservation of the correct protein-protein architecture that makes Crp to activate target promoters. These results, along with cognate gel retardation assays indicated that all basic features of the reference Crp(E. coli) protein are kept in the P. putida's counterpart, albeit operating under a different set of parameters, the extraordinarily high affinity for cAMP being the most noticeable. PMID- 22040087 TI - Patient safety culture measurement in general practice. Clinimetric properties of 'SCOPE'. AB - BACKGROUND: A supportive patient safety culture is considered to be an essential condition for improving patient safety. Assessing the current safety culture in general practice may be a first step to target improvements. To that end, we studied internal consistency and construct validity of a safety culture questionnaire for general practice (SCOPE) which was derived from a comparable questionnaire for hospitals (Dutch-HSOPS). METHODS: The survey was conducted among caregivers of Dutch general practice as part of an ongoing quality accreditation process using a 46 item questionnaire. We conducted factor analyses and studied validity by calculating correlations between the subscales and testing the hypothesis that respondents' patient safety grade of their practices correlated with their scores on the questionnaire. RESULTS: Of 72 practices 294 respondents completed the questionnaire. Eight factors were identified concerning handover and teamwork, support and fellowship, communication openness, feedback and learning from error, intention to report events, adequate procedures and staffing, overall perceptions of patient safety and expectations and actions of managers. Cronbach's alpha of the factors rated between 0.64 and 0.85. The subscales intercorrelated moderately, except for the factor about intention to report events. Respondents who graded patient safety highly scored significantly higher on the questionnaire than those who did not. CONCLUSIONS: The SCOPE questionnaire seems an appropriate instrument to assess patient safety culture in general practice. The clinimetric properties of the SCOPE are promising, but future research should confirm the factor structure and construct of the SCOPE and delineate its responsiveness to changes in safety culture over time. PMID- 22040088 TI - Ubiquitin and ubiquitin-modified proteins activate the Pseudomonas aeruginosa T3SS cytotoxin, ExoU. AB - Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that possesses a type III secretion system (T3SS) critical for evading innate immunity and establishing acute infections in compromised patients. Our research has focused on the structure-activity relationships of ExoU, the most toxic and destructive type III effector produced by P. aeruginosa. ExoU possesses phospholipase activity, which is detectable in vitro only when a eukaryotic cofactor is provided with membrane substrates. We report here that a subpopulation of ubiquitylated yeast SOD1 and other ubiquitylated mammalian proteins activate ExoU. Phospholipase activity was detected using purified ubiquitin of various chain lengths and linkage types; however, free monoubiquitin is sufficient in a genetically engineered dual expression system. The use of ubiquitin by a bacterial enzyme as an activator is unprecedented and represents a new aspect in the manipulation of the eukaryotic ubiquitin system to facilitate bacterial replication and dissemination. PMID- 22040090 TI - Bayesian adaptive approach to estimating sample sizes for seizures of illicit drugs. AB - A considerable amount of discussion can be found in the forensics literature about the issue of using statistical sampling to obtain for chemical analyses an appropriate subset of units from a police seizure suspected to contain illicit material. Use of the Bayesian paradigm has been suggested as the most suitable statistical approach to solving the question of how large a sample needs to be to ensure legally and practically acceptable purposes. Here, we introduce a hypergeometric sampling model combined with a specific prior distribution for the homogeneity of the seizure, where a parameter for the analyst's expectation of homogeneity (alpha) is included. Our results show how an adaptive approach to sampling can minimize the practical efforts needed in the laboratory analyses, as the model allows the scientist to decide sequentially how to proceed, while maintaining a sufficiently high confidence in the conclusions. PMID- 22040089 TI - Helicobacter pylori antigens as potential modulators of lymphocytes' cytotoxic activity. AB - Helicobacter pylori (H.p) colonizes human gastric mucosa and causes gastric and duodenal ulcer disease or gastric cancer. Various H.p compounds may modulate the host immune response in regards to tolerance of the infection or disease development. The aim of this study was to determine whether H.p lipopolysaccharide (LPS) and glycine acid extract antigens (GE) or E. coli LPS influence the cytotoxic activity of peripheral blood lymphocytes from H.p infected - H.p (+) or uninfected - H.p (-) individuals, in the presence or absence of exogenous interleukin (IL)12. Individual H.p status was defined by the urea breath test. Lymphocytes, stimulated or not with H.p, and control antigens, with or without IL-12, were used as effector cells and epithelial HeLa cells as targets. The cytotoxicity of lymphocytes was expressed as the percentage of dead target cells unable to reduce tetrazolium salt. The supernatants from HeLa/lymphocyte cultures were used for detection of the cellular cytotoxicity markers granzyme B and caspase 8. The natural cytotoxic activity of lymphocytes from H.p (+) was less than that of H.p (-) donors. This may have been due to fewer natural killer cells of CD3(-) CD56(+) Nkp46(+) phenotype in H.p (+) in comparison to H.p (-) subjects. H.p GE and standard E. coli LPS enhanced the cytotoxicity of lymphocytes towards target cells whereas H.p LPS downregulated this activity. The decrease in lymphocyte cytotoxicity in response to H.p LPS correlated with a lack of IL-2 and IL-12 production, inhibition of interferon gamma production, and low IL-10 secretion by mononuclear leukocytes. IL-12 significantly enhanced the natural as well as H.p LPS and H.p GE driven cytotoxic capacity of lymphocytes. In conclusion, H.p LPS may negatively modulate natural cytotoxic activity and cytokine secretion by immunocompetent cells and thus be involved in the maintenance of infection and development of gastric pathologies. PMID- 22040091 TI - Periodic projector augmented wave density functional calculations on the hexachlorobenzene crystal and comparison with the experimental multipolar charge density model. AB - The projector augmented wave (PAW) methodology has been used to calculate a high precision electron density distribution rho(r) for the hexachlorobenzene crystal phase. Implementing the calculation of the crystallographic structure factors in the VASP code has permitted one to obtain the theoretical multipolar rho(r). This electron density is compared with both the DFT electron density and the experimental multipolar model obtained from high-resolution X-ray diffraction data. This comparison has been carried out in intra- and intermolecular regions within the framework of the quantum theory of atoms-in-molecules (QTAIM) developed by Bader and co-workers. The characterization of the electron density in both C-Cl and Cl...Cl regions, as well as within the atomic basins, shows similar features for the three models. As a consequence, the observation of charge depletion and charge concentration regions around the halogen nuclei (along the C-Cl bonding axis and in the perpendicular plane, respectively) underlines the nature of halogen bonding in terms of electrophilic and nucleophilic interactions. PMID- 22040092 TI - Liver uptake of gold nanoparticles after intraperitoneal administration in vivo: a fluorescence study. AB - BACKGROUND: One particularly exciting field of research involves the use of gold nanoparticles (GNPs) in the detection and treatment of cancer cells in the liver. The detection and treatment of cancer is an area in which the light absorption and emission characteristics of GNPs have become useful. Currently, there are no data available regarding the fluorescence spectra or in vivo accumulation of nanoparticles (NPs) in rat liver after repeated administration. In an attempt to characterise the potential toxicity or hazards of GNPs in therapeutic or diagnostic use, the present study measured fluorescence spectra, bioaccumulation and toxic effects of GNPs at 3 and 7 days following intraperitoneal administration of a 50 MUl/day dose of 10, 20 or 50 nm GNPs in rats. METHODS: The experimental rats were divided into one normal group (Ng) and six experimental groups (G1A, G1B, G2A, G2B, G3A and G3B; G1: 20 nm; G2: 10 nm; G3: 50 nm; A: infusion of GNPs for 3 days; B: infusion of GNPs for 7 days). A 50 MUl dose of GNPs (0.1% Au by volume) was administered to the animals via intraperitoneal injection, and fluorescence measurements were used to identify the toxicity and tissue distribution of GNPs in vivo. Seventy healthy male Wistar-Kyoto rats were exposed to GNPs, and tissue distribution and toxicity were evaluated after 3 or 7 days of repeated exposure. RESULTS: After administration of 10 and 20 nm GNPs into the experimental rats, two fluorescence peaks were observed at 438 nm and 487 nm in the digested liver tissue. The fluorescence intensity for 10 and 20 nm GNPs (both first and second peaks) increased with the infusion time of GNPs in test rats compared to normal rats. The position of the first peak was similar for G1A, G2A, G1B, G2B, G3B and the normal (438 nm); that for G3A was shifted to a longer wavelength (444 nm) compared to the normal. The position of the second peak was similar for G1A, G1B, G2A, G2B and the control (487 nm), while it was shifted to a shorter wavelength for G3A (483 nm) and G3B (483 nm). The fluorescence intensity of the first and second peaks increased for G1A, G2A, G1B and G2B, while it decreased for G3A and G3B compared to the control. CONCLUSIONS: The fluorescence intensity of GNPs varied with the number, size and shape of particles and with the ratio of surface area to volume in a given sample. Fluorescence intensity changes during infusion depended on the size and shape of GNPs, with smaller particles experiencing larger changes during the infusion time in addition to the quenching produced by the larger GNPs. It is likely that smaller particles, which have a much higher ratio of surface area to volume compared to larger particles, are more prone to aggregation and surface interaction with biological components. This study suggests that fluorescence intensity can be used to evaluate bioaccumulation and the toxicity of gold nanoparticles in rats. PMID- 22040093 TI - Role of neutrophils in persistent airway obstruction due to refractory asthma. AB - BACKGROUND AND OBJECTIVE: One of the clinical manifestations of refractory asthma (RA) in a certain group of patients is persistent airway obstruction (PAO), despite treatment with high doses of inhaled and/or systemic corticosteroids. Airway neutrophilic inflammation is frequently observed in RA; however, the relationship between neutrophilic inflammation and PAO has not been evaluated in this group of patients. The aim of this study was to compare the clinical parameters and patterns of inflammatory cells between patients with or without PAO due to RA, and to identify the factors associated with PAO. METHODS: Seventy seven patients with RA were recruited from a cohort of 2298 asthmatic patients. Sputum differential cell counts were performed at initial presentation. Clinical and physiological parameters were compared between patients with (n = 19) or without PAO (n = 58). RESULTS: The group with PAO had a longer duration of asthma and a higher frequency of near-fatal asthma than the non-PAO group, although higher doses of inhaled corticosteroids were used in the PAO group (P = 0.037). Neutrophilic inflammation was predominant in the group with PAO, whereas eosinophilic inflammation was predominant in the non-PAO group (P = 0.003). When both groups were stratified according to smoking status, the non-smoking PAO group had the longest duration of asthma, with early onset of asthma (P < 0.05). The non-smoking PAO group tended to have the highest percentage of sputum neutrophils. Irrespective of smoking status, the percentage of sputum eosinophils was significantly higher in the non-PAO group than in the PAO group. CONCLUSIONS: Patients with PAO due to RA show different clinical manifestations when compared with those without PAO and have neutrophil-dominant airway inflammation. PMID- 22040095 TI - Microfluidic electrochemical array for detection of reactive metabolites formed by cytochrome P450 enzymes. AB - A novel, simple, rapid microfluidic array using bioelectronically driven cytochrome P450 enzyme catalysis for reactive metabolite screening is reported for the first time. The device incorporates an eight-electrode screen-printed carbon array coated with thin films of DNA, [Ru(bpy)(2)(PVP)(10)](ClO(4)) {RuPVP}, and rat liver microsomes (RLM) as enzyme sources. Catalysis features electron donation to cyt P450 reductase in the RLMs and subsequent cyt P450 reduction while flowing an oxygenated substrate solution past sensor electrodes. Metabolites react with DNA in the film if they are able, and damaged DNA is detected by catalytic square wave voltammetry (SWV) utilizing the RuPVP polymer. The microfluidic device was tested for a set of common pollutants known to form DNA-reactive metabolites. Logarithmic turnover rates based on SWV responses gave excellent correlation with the rodent liver TD(50) toxicity metric, supporting the utility of the device for toxicity screening. The microfluidic array gave much better S/N and reproducibility than single-electrode sensors based on similar principles. PMID- 22040096 TI - Three regimes of water adsorption in annealed silica opals and optical assessment. AB - Physisorbed and structurally bound (surface and internal) water in silica opals are distinguished and quantified by thermogravimetry. By controlled dehydroxylation with thermal annealing, we correlate these forms of water with the silica chemistry. In particular, we find that the silica capability to physically adsorb water from ambient moisture exhibits three regimes, associated with the distinct condensation behavior of bonded and unbonded surface silanols. Features in both opal IR absorbance and photonic band gap reproduce the physisorbed water regimes. This allows direct assessment of the water content and its evolution just by routine optical spectroscopy, being a useful tool for local and nondestructive analysis of colloidal silica. Besides, this provides a simple recipe for accurate tuning of the opal photonic band gap (about 10% in position and width) by just selecting the annealing temperature. PMID- 22040097 TI - Protein and mineral composition of osteogenic extracellular matrix constructs generated with a flow perfusion bioreactor. AB - This study investigated the temporal composition of an osteogenic extracellular matrix construct generated by culturing mesenchymal stem cells in an electrospun biodegradable poly(epsilon-caprolactone) fiber mesh scaffold within a flow perfusion bioreactor. Constructs of different extracellular matrix maturities were analyzed for their protein and mineral composition at several culture durations by liquid chromatography-tandem mass spectrometry, scanning electron microscopy, energy-dispersive X-ray diffraction, X-ray diffraction, and calcium and phosphate assays. The analysis revealed that at short culture durations the cells deposited cellular adhesion proteins as a prerequisite protein network for further bone formation. At the later culture durations, the extracellular matrix was composed of collagen 1, hydroxyapatite, matrix remodeling proteins, and regulatory proteins. These results suggest that the later culture duration constructs would allow for improved bone regeneration due to the ability to mineralize and the capabilities for future remodeling. PMID- 22040098 TI - Drug-inducing gynaecomastia--a critical review. AB - Gynaecomastia has been associated with a large variety of drugs in the literature. However, a causal relation of the incidence of gynaecomastia to a certain drug should be considered only if sufficient and significant evidence can be obtained from the studies published. In this review, studies quoted in Medline were evaluated according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system for clinical studies. Reports on 92 drugs were found in Medline in combination with gynaecomastia. An imbalance of the oestrogen/androgen ratio causes gynaecomastia. Also, prolactin has gynaecomastia-inducing properties. In 14 of the drugs quoted, the studies lead to a level of recommendation 'A'. All these drugs have been designed to interfere with the production and action of sexual hormones or of prolactin. In 25 of the drugs, the level of recommendation was 'B'. Besides those drugs in this group that have been designed for interference with the metabolism of steroid hormones or of prolactin, in drugs for acid-related disorders, diuretics, antiretroviral drugs, antimycotics, psychoanaleptics, alcohol gynaecomastia was described as an unexpected adverse effect. Studies on the association of drugs and gynaecomastia do not share a generally accepted definition of gynaecomastia; in this way, the informational value is limited. PMID- 22040099 TI - p-Cu2O-shell/n-TiO2-nanowire-core heterostucture photodiodes. AB - This study reports the deposition of cuprous oxide [Cu2O] onto titanium dioxide [TiO2] nanowires [NWs] prepared on TiO2/glass templates. The average length and average diameter of these thermally oxidized and evaporated TiO2 NWs are 0.1 to 0.4 MUm and 30 to 100 nm, respectively. The deposited Cu2O fills gaps between the TiO2 NWs with good step coverage to form nanoshells surrounding the TiO2 cores. The p-Cu2O/n-TiO2 NW heterostructure exhibits a rectifying behavior with a sharp turn-on at approximately 0.9 V. Furthermore, the fabricated p-Cu2O-shell/n-TiO2 nanowire-core photodiodes exhibit reasonably large photocurrent-to-dark-current contrast ratios and fast responses. PMID- 22040100 TI - Potent taccalonolides, AF and AJ, inform significant structure-activity relationships and tubulin as the binding site of these microtubule stabilizers. AB - The taccalonolides are a class of microtubule stabilizing agents isolated from plants of the genus Tacca. In efforts to define their structure-activity relationships, we isolated five new taccalonolides, AC-AF and H2, from one fraction of an ethanol extract of Tacca plantaginea. The structures were elucidated using a combination of spectroscopic methods, including 1D and 2D NMR and HR-ESI-MS. Taccalonolide AJ, an epoxidation product of taccalonolide B, was generated by semisynthesis. Five of these taccalonolides demonstrated cellular microtubule-stabilizing activities and antiproliferative actions against cancer cells, with taccalonolide AJ exhibiting the highest potency with an IC(50) value of 4.2 nM. The range of potencies of these compounds, from 4.2 nM to >50 MUM, for the first time provides the opportunity to identify specific structural moieties crucial for potent biological activities as well as those that impede optimal cellular effects. In mechanistic assays, taccalonolides AF and AJ stimulated the polymerization of purified tubulin, an activity that had not previously been observed for taccalonolides A and B, providing the first evidence that this class of microtubule stabilizers can interact directly with tubulin/microtubules. Taccalonolides AF and AJ were able to enhance tubulin polymerization to the same extent as paclitaxel but exhibited a distinct kinetic profile, suggesting a distinct binding mode or the possibility of a new binding site. The potencies of taccalonolides AF and AJ and their direct interaction with tubulin, together with the previous excellent in vivo antitumor activity of this class, reveal the potential of the taccalonolides as new anticancer agents. PMID- 22040101 TI - Inhibition of staphylothrombin by dabigatran reduces Staphylococcus aureus virulence. AB - BACKGROUND: Staphylocoagulase and von Willebrand binding protein (VWbp) bind to prothrombin to form the staphylothrombin complex that converts fibrinogen into fibrin. OBJECTIVES: To study the role of staphylothrombin and its inhibition by dabigatran on Staphylococcus aureus virulence. METHODS: We studied the effect of staphylothrombin inhibition on bacterial attachment to polystyrene surfaces, leukocyte activation and bactericidal activity for S. aureus ATCC 25923, S. aureus Newman, and staphylocoagulase- and VWbp-negative S. aureus Newman mutants in the presence or absence of prothrombin and fibrinogen. We measured the abscess size after subcutaneous (s.c.) injection of S. aureus ATCC 25923 and S. aureus Newman, as well as an S. aureus Newman mutant strain lacking staphylocoagulase and VWbp, in mice treated with either dabigatran or placebo. RESULTS: Staphylothrombin-mediated fibrin increased the association of S. aureus to polystyrene surfaces and reduced the bactericidal activity of leukocytes. The absence or inhibition of staphylothrombin decreased the bacterial association, enhanced leukocyte activation and reduced bacterial survival in vitro. Abscess size was smaller in mice treated with dabigatran or infected with a coagulase negative mutant. CONCLUSION: Inhibition or the absence of staphylothrombin reduced S. aureus virulence in in vitro and in vivo models. PMID- 22040102 TI - A comparison of X-ray and proton beam low energy secondary electron track structures using the low energy models of Geant4. AB - PURPOSE: Lethal cell damage by ionising radiation is generally initiated by the formation of complex strand breaks, resulting from ionisation clusters in the DNA molecule. A better understanding of the effect of the distribution of ionisation clusters within the cell and particularly in regard to DNA segments could be beneficial to radiation therapy treatment planning. Low energy X-rays generate an abundance of low energy electrons similar to that associated with MeV protons. The study and comparison of the track structure of photon and proton beams could permit the substitution of photon microbeams for single cell ion irradiations at proton facilities used to predict the relative biological effectiveness (RBE) of charged particle fields. MATERIALS AND METHODS: The track structure of X-ray photons is compared with proton pencil beams in voxels of approximate DNA strand size (2 * 2 * 5 nm). The Very Low Energy extension models of the Monte Carlo simulation toolkit GEometry ANd Tracking 4 (Geant4) is used. Simulations were performed in a water phantom for an X-ray and proton beam of energies 100 keV and 20 MeV, respectively. RESULTS: The track structure of the photon and proton beams are evaluated using the ionisation cluster size distribution as well as the radial dose deposition of the beam. CONCLUSIONS: A comparative analysis of the ionisation cluster distribution and radial dose deposition obtained is presented, which suggest that low energy X-rays could produce similar ionisation cluster distributions to MeV protons on the DNA scale of size at depths greater than ~10 MUm and at distances greater than ~1 MUm from the beam centre. Here the ionisation cluster size for each beam is less than ~100. The radial dose deposition is also approximately equal at large depths and at distances greater than 10 MUm from the beam centre. PMID- 22040103 TI - Gaining absolute control of the regiochemistry in the cobalt-catalyzed 1,4 hydrovinylation reaction. AB - The absolute control of the regiochemistry of a cobalt-catalyzed 1,4 hydrovinylation reaction is achieved by alternation of the ligands applied. While the dppe/dppp ligands led to the formation of the branched product, the herein described application of the SchmalzPhos ligand generates the corresponding linear product in both excellent yields and regioselectivities. The catalyst system exhibits a high tolerance toward functional groups, and the very mild reaction conditions allow the synthesis of 1,4-dienes without isomerization into conjugated systems. PMID- 22040104 TI - Effects of incretins on blood pressure: a promising therapy for type 2 diabetes mellitus with hypertension. AB - The prevalence of type 2 diabetes mellitus (T2DM) has increased markedly worldwide. A recent epidemiological study reported that approximately 63% of T2DM patients also have high blood pressure (>130/80 mmHg), which doubles their risk of cardiac events. Of the medications used to treat T2DM, the incretins are a group of peptides that not only regulate blood glucose effectively and moderately, but also protect patients against cardiovascular events and improve several cardiovascular parameters. Here were review data from preclinical and short- and long-term clinical studies investigating the antihypertensive effects of incretins. We also elucidate four possible mechanisms underlying the antihypertensive effects of incretins. We conclude that incretins can lower blood pressure of T2DM patients, independent of weight loss, and will surely improve the prognosis of these patients. PMID- 22040105 TI - Folding of a tryptophan zipper peptide investigated on the basis of the nuclear Overhauser effect and thermal denaturation. AB - Short, secondary-structure-containing peptides are suitable models for the study of protein folding due to their relative simplicity. Here, we investigate thermal denaturation of the tryptophan zipper peptide, trpzip4, a peptide that forms a beta-hairpin in solution. In order to monitor the thermal denaturation of peptides or small proteins, chemical shift values of H(alpha) or H(N) may be used. However, various factors other than secondary structure can influence chemical shift values, such as side-chain orientation of nearby aromatic residues. Nuclear Overhauser effect (NOE) intensity from backbone interproton cross peaks is an alternative way to study thermal denaturation, as long as various factors that give rise to a change in NOE intensity upon changing the temperature are considered. As a relative indicator for denaturation, we define a cutoff temperature, where half of the initial NOE intensity is lost for each backbone interproton cross peak. For trpzip4, this cutoff temperature is highest for residues in the central part of the structure and lowest for residues near the termini. These observations support the notion that the structure of the trpzip4 peptide is stabilized by a hydrophobic cluster formed by tryptophan residues located in the central region of the beta-hairpin. PMID- 22040108 TI - Myocardial improvement with human embryonic stem cell-derived cardiomyocytes enriched by p38MAPK inhibition. AB - BACKGROUND AIMS: We have shown previously that inhibition of the p38 mitogen activated protein kinase (p38MAPK) directs the differentiation of human embryonic stem cell (hESC)-derived cardiomyocytes (hCM). We investigated the therapeutic benefits of intramyocardial injection of hCM differentiated from hESC by p38MAPK inhibition using closed-chest ultrasound-guided injection at a clinically relevant time post-myocardial infarction (MI) in a mouse model. METHODS: MI was induced in mice and the animals treated at day 3 with: (a) hCM, (b) human fetal fibroblasts (hFF) as cell control, or (c) medium control (n = 10 animals/group). Left ventricular ejection fraction (LVEF) was evaluated post-MI prior to therapy, and at days 28 and 60 post-cell therapy. Hearts were analyzed at day 60 for infarct size, angiogenesis, cell fate and teratoma formation. RESULTS: LVEF was improved in the hCM-treated animals compared with both hFF and medium control treated animals at day 28 (39.03 +/- 1.79% versus 27.89 +/- 1.27%, P < 0.05, versus 32.90 +/- 1.46%, P < 0.05, respectively), with sustained benefit until day 60. hCM therapy resulted in significantly smaller scar size, increased capillary bed area, increased number of arterioles, less native cardiomyocyte (CM) apoptosis, and increased CM proliferation compared with the other two groups. These benefits were achieved despite a very low retention rate of the injected cells at day 60, as assessed by immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). Therapy with hCM did not result in intramyocardial teratoma formation at day 60. CONCLUSIONS: This study demonstrates that hCM derived from p38MAPK-treated hESC have encouraging therapeutic potential. PMID- 22040109 TI - Early endothelial progenitor cells in bone marrow are a biomarker of cell therapy success in patients with critical limb ischemia. AB - BACKGROUND AIMS: Endothelial progenitor cells (EPC) have been proposed for autologous angiogenic therapy. The objectives of this study were to quantify EPC in the peripheral blood and bone marrow mononuclear cells (BM-MNC) of patients with critical limb ischemia that had received BM-MNC as a cell therapy product, and to study the putative relationship between the presence of EPC and the process of neovascularization in toe or transmetatarsal amputation specimens. METHODS: Early and late endothelial progenitor cells (CFU-EC and ECFC) were cultivated and quantified according to published methods in peripheral blood and BM-MNC from patients with critical limb ischemia (CLI; n = 11) enrolled in the OPTIPEC trial ( http://clinicaltrials.gov/ct2/show/NCT00377897 ) to receive BM MNC as a cell therapy product. RESULTS: Eight out of the 11 patients had undergone amputations. Three of the patients displayed a neoangiogenic process that was associated with a higher number of CFU-EC in BM-MNC, while CD3+ , CFU-GM and CD34+ in BM-MNC, and EPC in peripheral blood, did not correlate with the appearance of newly formed vessels. As expected, circulating CFU-EC and ECFC counts were significantly lower in CLI patients compared with age-matched controls. CONCLUSIONS: In patients with critical limb ischemia, EPC in peripheral blood were decreased compared with healthy individuals. However, in BM-MNC we found that relative numbers of CFU-EC could be used as an indicator to discriminate patients with neoangiogenic processes. These results need to be confirmed in a randomized study. PMID- 22040110 TI - Placental mesenchymal stromal cells induced into neurotrophic factor-producing cells protect neuronal cells from hypoxia and oxidative stress. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSC) may be useful in a range of clinical applications. The placenta has been suggested as an abundant, ethically acceptable, less immunogenic and easily accessible source of MSC. The aim of this study was to evaluate the capacity of induced placental MSC to differentiate into neurotrophic factor-producing cells (NTF) and their protective effect on neuronal cells. METHODS: MSC were isolated from placentas and characterized by fluorescence-activated cell sorting (FACS). The cells underwent an induction protocol to differentiate them into NTF. Analysis of the cellular differentiation was done using polymerase chain reactions (PCR), immunocytochemical staining and enzyme-linked immunosorbent assays (ELISA). Conditioned media from placental MSC (PL-MSC) and differentiated MSC (PL-DIFF) were collected and examined for their ability to protect neural cells. RESULTS: The immunocytochemical studies showed that the cells displayed typical MSC membrane markers. The cells differentiated into osteoblasts and adipocytes. PCR and immunohistology staining demonstrated that the induced cells expressed typical astrocytes markers and neurotrophic factors. Vascular endothelial growth factor (VEGF) levels were higher in the conditioned media from PL-DIFF compared with PL-MSC, as indicated by ELISA. Both PL-DIFF and PL-MSC conditioned media markedly protected neural cells from oxidative stress induced by H(2)O(2) and 6-hydroxydopamine. PL-DIFF conditioned medium had a superior effect on neuronal cell survival. Anti-VEGF antibodies (Bevacizumab) reduced the protective effect of the conditioned media from differentiated and undifferentiated MSC. CONCLUSIONS: This study has demonstrated a neuroprotective effect of MSC of placental origin subjected to an induction differentiation protocol. These data offer the prospect of using placenta as a source for stem cell-based therapies. PMID- 22040111 TI - The contribution of home-based technology to older people's quality of life in extra care housing. AB - BACKGROUND: British government policy for older people focuses on a vision of active ageing and independent living. In the face of diminishing personal capacities, the use of appropriate home-based technology (HBT) devices could potentially meet a wide range of needs and consequently improve many aspects of older people's quality of life such as physical health, psychosocial well-being, social relationships, and their physical or living environment. This study aimed to examine the use of HBT devices and the correlation between use of such devices and quality of life among older people living in extra-care housing (ECH). METHODS: A structured questionnaire was administered for this study. Using purposive sampling 160 older people living in extra-care housing schemes were selected from 23 schemes in England. A face-to-face interview was conducted in each participant's living unit. In order to measure quality of life, the SEIQoL Adapted and CASP-19 were used. RESULTS: Although most basic appliances and emergency call systems were used in the living units, communally provided facilities such as personal computers, washing machines, and assisted bathing equipment in the schemes were not well utilised. Multiple regression analysis adjusted for confounders including age, sex, marital status, living arrangement and mobility use indicated a coefficient of 1.17 with 95% CI (0.05, 2.29) and p = 0.04 [SEIQoL-Adapted] and 2.83 with 95% CI (1.17, 4.50) and p = 0.001 [CASP-19]. CONCLUSIONS: The findings of the present study will be value to those who are developing new form of specialised housing for older people with functional limitations and, in particular, guiding investments in technological aids. The results of the present study also indicate that the home is an essential site for developing residential technologies. PMID- 22040112 TI - Hydrolysis of serine-containing peptides at neutral pH promoted by [MoO4]2- oxyanion. AB - Hydrolysis of the dipeptides glycylserine (GlySer), leucylserine (LeuSer), histidylserine (HisSer), glycylalanine (GlyAla), and serylglycine (SerGly) was examined in oxomolybdate solutions by means of (1)H, (13)C, and (95)Mo NMR spectroscopy. In the presence of a mixture of oxomolybdates, the hydrolysis of the peptide bond in GlySer proceeded under neutral pD conditions (pD = 7.0, 60 degrees C) with a rate constant of k(obs) = 5.9 * 10(-6) s(-1). NMR spectra did not show evidence of the formation of paramagnetic species, excluding the possibility of Mo(VI) reduction to Mo(V), indicating that the cleavage of the peptide bond is purely hydrolytic. The pD dependence of k(obs) exhibits a bell shaped profile, with the fastest cleavage observed at pD 7.0. Comparison of the rate profile with the concentration profile of oxomolybdate species implicated monomolybdate MoO(4)(2-) as the kinetically active complex. Kinetics experiments at pD 7.0 using a fixed amount of GlySer and increasing amounts of MoO(4)(2-) allowed for calculation of the catalytic rate constant (k(2) = 9.25 * 10(-6) s( 1)) and the formation constant for the GlySer-MoO(4)(2-) complex (K(f) = 15.25 M( 1)). The origin of the hydrolytic activity of molybdate is most likely a combination of the polarization of amide oxygen in GlySer due to the binding to molybdate, followed by the intramolecular attack of the Ser hydroxyl group. PMID- 22040114 TI - O-H stretch overtone excitation of ethyl hydroperoxide conformers. AB - We present laser photoacoustic spectra of ethyl hydroperoxide (EHP) for 3-6 quanta of O-H stretch. Spectra are consistent with ab initio spectral simulations that take into account the influence of torsional motion about the O-O bond on O H stretch overtone excitation. Experimental and simulated spectra share two trends. First, spectral features due to torsional excitation, including hot bands, become more prominent with increasing O-H stretch excitation, as has been shown previously for similar molecules such as methyl hydroperoxide. Second, contributions from the two different EHP conformers become clearly distinguishable at higher O-H stretch excitation, mainly due to the role of torsional motion. Results are consistent with a higher energy separation (330 cm( 1)) between the lower energy anti and the higher energy gauche conformers than predicted by electronic structure calculations (137 cm(-1)). Calculated absorption intensities are consistently higher than experimental values by ~30% but within the experimental uncertainty. With each additional O-H stretch overtone, the dropoff in calculated integrated absorption intensities at room temperature becomes less extreme, with a 14-fold dropoff from 3nu(OH) to 4nu(OH) and an 8-fold decrease from 5nu(OH) to 6nu(OH). PMID- 22040113 TI - Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity. AB - Fusobacterium nucleatum is a Gram-negative oral anaerobe, capable of systemic dissemination causing infections and abscesses, often in mixed-species, at different body sites. We have shown previously that F. nucleatum adheres to and invades host epithelial and endothelial cells via a novel FadA adhesin. In this study, vascular endothelial (VE)-cadherin, a member of the cadherin family and a cell-cell junction molecule, was identified as the endothelial receptor for FadA, required for F. nucleatum binding to the cells. FadA colocalized with VE-cadherin on endothelial cells, causing relocation of VE-cadherin away from the cell-cell junctions. As a result, the endothelial permeability was increased, allowing the bacteria to cross the endothelium through loosened junctions. This crossing mechanism may explain why the organism is able to disseminate systemically to colonize in different body sites and even overcome the placental and blood-brain barriers. Co-incubation of F. nucleatum and Escherichia coli enhanced penetration of the endothelial cells by the latter in the transwell assays, suggesting F. nucleatum may serve as an 'enabler' for other microorganisms to spread systemically. This may explain why F. nucleatum is often found in mixed infections. This study reveals a possible novel dissemination mechanism utilized by pathogens. PMID- 22040116 TI - Prof. dr.h.van. genderen's farewell. PMID- 22040115 TI - Spatially balanced sampling through the pivotal method. AB - A simple method to select a spatially balanced sample using equal or unequal inclusion probabilities is presented. For populations with spatial trends in the variables of interest, the estimation can be much improved by selecting samples that are well spread over the population. The method can be used for any number of dimensions and can hence also select spatially balanced samples in a space spanned by several auxiliary variables. Analysis and examples indicate that the suggested method achieves a high degree of spatial balance and is therefore efficient for populations with trends. PMID- 22040118 TI - The role of microcystins in maintaining colonies of bloom-forming Microcystis spp. AB - Microcystis is a cosmopolitan genus of cyanobacteria and occurs in many different forms. Large surface blooms of the cyanobacterium are well known in eutrophic lakes throughout the globe. We evaluated the role of microcystins (MCs) in promoting and maintaining bloom-forming cell aggregates at environmentally relevant MC concentrations (0.25-10 ug l(-1)). MCs significantly enhanced Microcystis colony sizes. Colonial diameters in microcystin-RR (MC-RR)-treated cultures (at 1 ug l(-1)) were significantly larger than control colonies, by factors of 1.5, 2.6 and 2.7 in Microcystis wesenbergii DC-M1, M. ichthyoblabe TH M1 and Microcystis sp. FACHB1027 respectively. Depletion of extracellular MC concentrations caused Microcystis colony size to decrease, suggesting that released MCs are intimately involved in the maintenance of Microcystis colonial size. MC-RR exposure did not influence Microcystis growth rate, but did significantly increase the production of extracellular polysaccharides (EPS). In addition, MC-RR exposure appeared to trigger upregulation of certain parts of four polysaccharide biosynthesis-related genes: capD, csaB, tagH and epsL. These results strongly indicate that induction of polysaccharides by MC-RR was the major mechanism through which MCs enhanced colony formation in Microcystis spp. Cellular release of MCs, therefore, may play a key role in the persistence of algal colonies and the dominance of Microcystis. PMID- 22040119 TI - Reliability of maximal isometric knee strength testing with modified hand-held dynamometry in patients awaiting total knee arthroplasty: useful in research and individual patient settings? A reliability study. AB - BACKGROUND: Patients undergoing total knee arthroplasty (TKA) often experience strength deficits both pre- and post-operatively. As these deficits may have a direct impact on functional recovery, strength assessment should be performed in this patient population. For these assessments, reliable measurements should be used. This study aimed to determine the inter- and intrarater reliability of hand held dynamometry (HHD) in measuring isometric knee strength in patients awaiting TKA. METHODS: To determine interrater reliability, 32 patients (81.3% female) were assessed by two examiners. Patients were assessed consecutively by both examiners on the same individual test dates. To determine intrarater reliability, a subgroup (n = 13) was again assessed by the examiners within four weeks of the initial testing procedure. Maximal isometric knee flexor and extensor strength were tested using a modified Citec hand-held dynamometer. Both the affected and unaffected knee were tested. Reliability was assessed using the Intraclass Correlation Coefficient (ICC). In addition, the Standard Error of Measurement (SEM) and the Smallest Detectable Difference (SDD) were used to determine reliability. RESULTS: In both the affected and unaffected knee, the inter- and intrarater reliability were good for knee flexors (ICC range 0.76-0.94) and excellent for knee extensors (ICC range 0.92-0.97). However, measurement error was high, displaying SDD ranges between 21.7% and 36.2% for interrater reliability and between 19.0% and 57.5% for intrarater reliability. Overall, measurement error was higher for the knee flexors than for the knee extensors. CONCLUSIONS: Modified HHD appears to be a reliable strength measure, producing good to excellent ICC values for both inter- and intrarater reliability in a group of TKA patients. High SEM and SDD values, however, indicate high measurement error for individual measures. This study demonstrates that a modified HHD is appropriate to evaluate knee strength changes in TKA patient groups. However, it also demonstrates that modified HHD is not suitable to measure individual strength changes. The use of modified HHD is, therefore, not advised for use in a clinical setting. PMID- 22040120 TI - The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo. AB - BACKGROUND: The initial pharmacokinetic study of a new anticancer agent (OC-6-43) bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins that serve as markers of LA-12 treatment, response and therapy monitoring. METHODS: Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) in 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis. RESULTS: We identified Retinol-binding protein 4 (RBP4) whose level correlated with LA-12 level in treated rats. Similar results were observed in randomly selected patients involved in Phase I clinical trials. CONCLUSIONS: RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs. PMID- 22040121 TI - Microbial resistance in relation to catalase activity to oxidative stress induced by photolysis of hydrogen peroxide. AB - The purpose of the present study was to evaluate the mechanism of microbial resistance to oxidative stress induced by photolysis of hydrogen peroxide (H(2)O(2)) in relation to microbial catalase activity. In microbicidal tests, Staphylococcus aureus and Candida albicans were killed and this was accompanied by production of hydroxyl radicals. C. albicans was more resistant to hydroxyl radicals generated by photolysis of H(2)O(2) than was S. aureus. A catalase activity assay demonstrated that C. albicans had stronger catalase activity; accordingly, catalase activity could be one of the reasons for the resistance of the fungus to photolysis of H(2)O(2). Indeed, it was demonstrated that C. albicans with strong catalase activity was more resistant to photolysis of H(2)O(2) than that with weak catalase activity. Kinetic analysis using a modified Lineweaver-Burk plot also demonstrated that the microorganisms reacted directly with hydroxyl radicals and that this was accompanied by decomposition of H(2)O(2). The results of the present study suggest that the microbicidal effects of hydroxyl radicals generated by photolysis of H(2)O(2) can be alleviated by decomposition of H(2)O(2) by catalase in microorganisms. PMID- 22040122 TI - Identification of binding sites for acetaldehyde adsorption on titania nanorod surfaces using CIMS. AB - The interaction of acetaldehyde with TiO(2) nanorods has been studied under low pressures (acetaldehyde partial pressure range 10(-4)-10(-8) Torr) using chemical ionization mass spectrometry (CIMS). We quantitatively separate irreversible adsorption, reversible adsorption, and an uptake of acetaldehyde assigned to a thermally activated surface reaction. We find that, at room temperature and 1.2 Torr total pressure, 2.1 +/- 0.4 molecules/nm(2) adsorb irreversibly, but this value exhibits a sharp decrease as the analyte partial pressure is lowered below 4 * 10(-4) Torr, regardless of exposure time. The number of reversible binding sites at saturation amounts to 0.09 +/- 0.02 molecules/nm(2) with a free energy of adsorption of 43.8 +/- 0.2 kJ/mol. We complement our measurements with FTIR spectroscopy and identify the thermal dark reaction as a combination of an aldol condensation and an oxidative adsorption that converts acetaldehyde to acetate or formate and CO, at a measured combined initial rate of 7 +/- 1 * 10(-4) molecules/nm(2) s. By characterizing binding to different types of sites under dark conditions in the absence of oxygen and gas phase water, we set the stage to analyze site-specific photoefficiencies involved in the light-assisted mineralization of acetaldehyde to CO(2). PMID- 22040123 TI - Pathologic evaluation of the cervical spine following surgical and chiropractic interventions. AB - When patients die after chiropractic or surgical interventions of the cervical spine, pathologists tasked with the autopsy are frequently overwhelmed by the complicated anatomy, laborious dissections, complex operative procedures and surgical hardware, and the necessity to differentiate artifacts from trauma and disease. However, abundant data can be obtained from careful evaluation of the cervical spine in situ; extensive postmortem diagnostic imaging procedures; detailed dissections of the removed, formalin-fixed and decalcified spine; and histology. This study presents a regimented, stepwise approach to the evaluation of the cervical spine in these difficult cases, promotes uniform assessment, facilitates diagnoses, and supports the accumulation of otherwise hard-to-come-by reference material that can be of value in future cases. The resultant detailed autopsy findings may prove useful in the medico-legal death investigation process. Autopsy findings may also be of great value to health care providers involved in quality assurance processes. PMID- 22040124 TI - High-efficiency GaAs and GaInP solar cells grown by all solid-state molecular beam-epitaxy. AB - We report the initial results of GaAs and GaInP solar cells grown by all solid state molecular-beam-epitaxy (MBE) technique. For GaAs single-junction solar cell, with the application of AlInP as the window layer and GaInP as the back surface field layer, the photovoltaic conversion efficiency of 26% at one sun concentration and air mass 1.5 global (AM1.5G) is realized. The efficiency of 16.4% is also reached for GaInP solar cell. Our results demonstrate that the MBE grown phosphide-contained III-V compound semiconductor solar cell can be quite comparable to the metal-organic-chemical-vapor-deposition-grown high-efficiency solar cell. PMID- 22040125 TI - A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis. AB - BACKGROUND AND OBJECTIVE: A disintegrin and metalloproteinase (ADAM) 33 is a susceptibility gene associated with inflammatory lung and skin diseases. It is selectively expressed in mesenchymal cells, and its metalloprotease activity has been linked to angiogenesis and tissue remodelling. A soluble form of ADAM33 (sADAM33) has been identified in the bronchoalveolar lavage fluid (BALF) of asthmatic patients, and its levels inversely correlate with lung function. Because of its association with inflammatory lung diseases, it was hypothesized that sADAM33 is elevated in BALF of patients with pulmonary sarcoidosis. METHODS: After removal of Ig using Protein A/G and enrichment using Concanavalin A beads, sADAM33 was identified in BALF by Western blotting. A fluorescence resonance energy transfer peptide cleavage assay was used to assess ADAM33-like activity in BALF. RESULTS: sADAM33 protein in BALF was detected as a 25 kDa fragment, and levels were significantly increased in samples from sarcoid patients when compared to healthy controls (P < 0.05). Levels of sADAM33 were inversely correlated with lung function (FVC%) (P < 0.05) and DL(CO) % predicted (P < 0.01). No difference in sADAM33 enzymatic activity was observed between healthy and sarcoid BALF samples. CONCLUSIONS: Release of sADAM33 is increased in sarcoid and may be associated with abnormal lung function. sADAM33 may be a biomarker of lung tissue inflammation and remodelling in sarcoid. PMID- 22040126 TI - Impurity profiling to match a nerve agent to its precursor source for chemical forensics applications. AB - Chemical forensics is a developing field that aims to attribute a chemical (or mixture) of interest to its source by the analysis of the chemical itself or associated material constituents. Herein, for the first time, trace impurities detected by gas chromatography/mass spectrometry and originating from a chemical precursor were used to match a synthesized nerve agent to its precursor source. Specifically, six batches of sarin (GB, isopropyl methylphosphonofluoridate) and its intermediate methylphosphonic difluoride (DF) were synthesized from two commercial stocks of 97% pure methylphosphonic dichloride (DC); the GB and DF were then matched by impurity profiling to their DC stocks from a collection of five possible stocks. Source matching was objectively demonstrated through the grouping by hierarchal cluster analysis of the GB and DF synthetic batches with their respective DC precursor stocks based solely upon the impurities previously detected in five DC stocks. This was possible because each tested DC stock had a unique impurity profile that had 57% to 88% of its impurities persisting through product synthesis, decontamination, and sample preparation. This work forms a basis for the use of impurity profiling to help find and prosecute perpetrators of chemical attacks. PMID- 22040127 TI - Activation of neurokinin-1 receptors up-regulates substance P and neurokinin-1 receptor expression in murine pancreatic acinar cells. AB - Acute pancreatitis (AP) has been associated with an up-regulation of substance P (SP) and neurokinin-1 receptor (NK1R) in the pancreas. Increased SP-NK1R interaction was suggested to be pro-inflammatory during AP. Previously, we showed that caerulein treatment increased SP/NK1R expression in mouse pancreatic acinar cells, but the effect of SP treatment was not evaluated. Pancreatic acinar cells were obtained from pancreas of male swiss mice (25-30 g). We measured mRNA expression of preprotachykinin-A (PPTA) and NK1R following treatment of SP (10( 6) M). SP treatment increased PPTA and NK1R expression in isolated pancreatic acinar cells, which was abolished by pretreatment of a selective NK1R antagonist, CP96,345. SP also time dependently increased protein expression of NK1R. Treatment of cells with a specific NK1R agonist, GR73,632, up-regulated SP protein levels in the cells. Using previously established concentrations, pre treatment of pancreatic acinar cells with Go6976 (10 nM), rottlerin (5 MUM), PD98059 (30 MUM), SP600125 (30 MUM) or Bay11-7082 (30 MUM) significantly inhibited up-regulation of SP and NK1R. These observations suggested that the PKC ERK/JNK-NF-kappaB pathway is necessary for the modulation of expression levels. In comparison, pre-treatment of CP96,345 reversed gene expression in SP-induced cells, but not in caerulein-treated cells. Overall, the findings in this study suggested a possible auto-regulatory mechanism of SP/NK1R expression in mouse pancreatic acinar cells, via activation of NK1R. Elevated SP levels during AP might increase the occurrence of a positive feedback loop that contributes to abnormally high expression of SP and NK1R. PMID- 22040128 TI - Near-infrared fluorescent nanocapsules with reversible response to thermal/pH modulation for optical imaging. AB - Polymeric near-infrared (NIR) fluorescent nanocapsules were developed, of which the fluorescence exhibited reversible response to local thermal/pH modulation. Our strategy was to use polymeric micelles made of temperature-sensitive Pluronic F-127 to encapsulate an amphiphilic NIR fluorescent dye-indocyanine green (ICG) within the core and then cross-link the micelle corona by pH-sensitive poly(ethylenimine) (PEI). The size swelling/shrinking property of the micelles induced by temperature decrease/increase was used as a switch to control the fluorescence yield of the nanocapsules. It was found that the fluorescence yield significantly increased with the increase in temperature. The PEI cross-link made the fluorescence yield also sensitive to local pH change and enhanced intracellular delivery of the nanocapsules as well. Preliminary results suggest the NIR fluorescent probes could be potentially used as a contrast agent sensitive to local environment for translational optical imaging/sensing. PMID- 22040129 TI - An improved model for teaching use of electronic apex locators. AB - AIM: To develop a simple, practical and inexpensive model, which enables the use of electronic apex locators (EALs) during pre-clinical and continuing education. METHODOLOGY: Extracted teeth were placed in a mould and embedded in acrylic resin. The resin was applied in two consecutive steps to form a cavity around the root apices. A closable plastic tube serves as a valve, and a steel wire connects to the EAL. RESULTS: With its semi-closed reservoir for conductive fluids surrounding the root apices, the new model enables working length measurements of root canals using EALs. CONCLUSIONS: The model simulates the clinical situation for endodontic teaching purposes, as it allows working length determination of root canals as recommended. The measuring results of the EAL can be verified by radiography. At the same time, the roots are not directly visible and accessible to the user, allowing a precise evaluation and grading of the treatment. PMID- 22040130 TI - The shortage of essential chemotherapy drugs in the United States. PMID- 22040131 TI - [Biomedical update in bioethics: a primordial ethical imperative]. AB - In this brief article we continue our reflection about the relations that should exist between the knowledge of biomedical sciences and the development of bioethics. After stating the principle of not absolute concordance between empirical and philosophical data as well as the former data are partial truths and highly contextualized by the experiment, we propose a certain criteria that should govern the use of biomedical sciences in bioethics. These criteria are based on ability to distinguish the two areas of knowledge and, without confusing each other, achieve their integration in a new unit of knowledge. Approximating the two disciplines in this way each will be more able to accommodate the other. From contiguity to integration into a higher order unit, without that both losing their own nature. We conclude that not only this posture avoid the mistake of deducting the bioethics from experimental scientific date but also not to manipulate biomedical data based on previous philosophical positions. Furthermore we also reached a more comprehensive and real understanding of bioethics. This implies that both scientists and humanists that work in bioethics must live an ethical imperative in their research that we have described as essential. This consist in a continuously update in biomedicine for research and development the bioethics. PMID- 22040132 TI - [Retraction of papers in bioethics: proposal for a paradigmatic case]. AB - The phenomenon of ethically deficient publication in the field of bioethics is practically unknown. In contrast to the numerous articles and regulations on the ethics of biomedical publications, there is a practical absence of articles devoted to consider the nature, types and prevalence of ethically defective publications in the bioethical literature. No regulatory framework for misbehavior in this field has been proposed until now. Certainly, this is a difficult subject. On one side, it is not easy to draw the ethical limits of the freedoms of thought and expression in bioethics, a discipline that flourishes in the open debate of principles, norms, cases, and imaginary scenarios, where the boundaries between rhetoric and misrepresentation are frequently blurred. After showing some examples of minor violations taken from the literature, the author deals with the moral duty to retract fraudulent bioethical articles, especially when they include deliberate distortions of the data or conclusions from published biomedical research. A detailed analysis of a fraudulent article is made (Haring B. "New Dimensions of Responsible Parenthood. " Theological Studies 37, (1976), 120-132), in which an almost systematic distortion of data and opinions of the cited literature has been made. The article, published in a time of intense and critical protest against the encyclical Humanae vitae, pretends to condemn the methods of natural family planning, the only acceptable means to the Pope, on the allegation that those methods were harmful for the embryo and fetus. According to the author, the retraction of Haring's article is necessary. PMID- 22040133 TI - [Bias in publications about the mechanism of action of the morning-after pill]. AB - The morning-after pill or ECP (levonorgestrel) first came into use in the late 20th century, but has only become widely available in the last ten years. Its introduction has been facilitated by health policies which have led to the removal of certain obstacles hindering its use. In this context, sociological, statistical and scientific data have been employed which have often turned out to be biased or partial in nature. The reliability of the information provided by health authorities, pharmaceutical companies and other social entities has been called into question in various respects, particularly as far as the mechanism of action, side effects and pregnancy rate are concerned. This study focuses on the mechanism by which levonorgestrel acts, since a wider discussion would fall beyond the scope of a single study, and the mechanism of action is the aspect which is least understood and most controversial. It remains to be determined whether levonorgestrel is a product which only acts prior to ovulation or which has an effect on the human embryo. PMID- 22040134 TI - [Estrogens and feminine brain maturation during adolescence: emergency contraceptive pill]. AB - In the period between puberty and maturity takes place the process of brain maturation. Hormone levels induce changes in neurons and direct the architecture and structural functionality thus affecting patterns of development of different brain areas. The onset of puberty brings with it the invasion of the female brain by high levels of hormones, cyclic surges of estrogen and progesterone in addition to steroids produced in situ. Control centers of emotions (amygdala), memory and learning (hippocampus) and sexual activity (hypothalamus) are modified according to the cyclical concentrations of both hormones. Sex hormones stimulate multimodal actions, both short and longer terms, because neurons in various brain areas have different types of receptors, membrane, cytoplasmic and nuclear. The composition of emergency contraceptive pill (postcoital pill) with high hormonal content raises the urgency of a thorough knowledge about the possible effect that the lack of control of the menstrual cycle in a time of consolidation of brain maturation, can bring in structuring and development of brain circuitry. Changes in the availability of sex steroids during puberty and adolescence underlie psychiatric disorders whose prevalence is typically feminine, such as depression, anxiety disorders. It is a fundamental ethical duty to present scientific data about the influence of estrogen in young female brain maturation, both for full information to potential users, and also to induce the appropriate public health measures. PMID- 22040135 TI - [Assisted human reproduction techniques: determination of parentage and users in comparative law]. AB - The paper undertakes the determination of parentage and users of assisted reproduction techniques in comparative law, particularly in three European Union countries: Italy, France and Spain. The idea of artificially conceived child protection, present in the Italian provision, is substituted, partially in French law, and totally in Spanish law, by an exclusively individualistic outlook, configuring a true "right to maternity" for married women and for those not living with a male partner (single women, divorced or widowed) or with a female partner (lesbians), and for women inseminated artificially by the semen of the husband before or after their death, and for women already having culminated their fertile life. PMID- 22040136 TI - [Proposals for social policies to improve the quality of life in attention deficit/hyperactivity disorder [ADHD]]. AB - This article describes the effects of pre and postnatal stress on the cerebral morphological findings described as attention deficit/hyperactivity disorder. [ADHD]. The consequences of ADHD cause social problems because these children have difficulties with family, school and social integration. Previous treatments are reviewed up to the present day. The drug that has been used most frequently is Metilphenidate, a psychostimulant, and recently, a new drug, Atomoxetine, a non psychostimulant was introduced. The therapy is combined with physiological training. These drugs give relief to the symptoms but their long term side effects are unknown. Recent investigations have shown that children with ADHD who are receiving either cognitive or control training have increased cerebral activity without previous medication. With these facts in mind the European ADHD Guidelines group suggests a new focus of attention on the children and adults with this problem with the aim of modifying the treatment followed until now. The ethical motives for this review are: a) to make society more aware of the problems of ADHD with the aim of taking measures to avoid the possible causes of the illness; b) to take into account that the effects of long term psychostimulant drugs on the developing mind are unknown; c) to gather information that supports the view that diagnosis of ADHD has increased. PMID- 22040137 TI - [Select embryos: preimplantation genetic diagnosis]. AB - The ability to detect chromosomal or genetic defects in embryos in vitro, associated with assisted human reproduction techniques before his possible transfer to the uterus to complete its development was presented as an alternative to eugenic abortion. And an option for older women to procreate, to avoid pregnancy of embryos with chromosomal defects. Genetic diagnosis before implantation (PGD) and screening of embryos in vitro (by the acronym, PSC), offers the image of the disabled person as an individual excluded from society. It assumes a direct human experimentation without therapeutic purposes or to manipulate the embryo that is chosen or discarded according to diagnosis or for advancement in perinatal medicine. Because these techniques can have multiple embryos, eugenics has also generated a "positive eugenics" that seeks to select embryos according to a third party, having certain characteristics, sex, or lack of predisposition to disease. Several issues demand unavoidable ethical duty to report on this form of eugenics, in addition to be directly and intentionally directed to destroy human life in its early stages, and does not meet the minimum requirements of rigorous scientific research or biotechnology. There have been no previous animal tests to validate the techniques so that there are serious errors in diagnosis with false positives and false negatives. Recently it has been shown that some discarded embryos can eliminate their detected defects two days after the biopsy. Moreover, the study about what may or may not be diagnosed is retrospective and unrecoverable damage. And, of particular importance is the fact that it is not known with certainty the effects that an embryo biopsy may cause to those diagnosed. PMID- 22040138 TI - [Delay the age of procreation, decline in fertility and increased use of assisted reproduction: risk of birth defects]. AB - In recent years there has been a progressive decline in fertility, originated mainly on women by the aging of ovules and on man through changes in genetic material of sperm due to cumulative environmental factors over time. Infertility treatments and techniques of assisted reproduction, IVF or insemination, consist of, or preceded by ovarian stimulation treatment aimed to obtain a large number of mature ovules in one cycle. This stimulation does not resolve the crucial issue of changing the pattern of chemical modification, parental imprinting, which occurs in the epigenetic process of oogenesis. Ovules induced to mature and / or forced to fertilization, do not to provide a fresh genome to be passed in each generation passes from parents to children. These changes affect the regulation of expression of a gene cluster (known as imprinted genes) during embryonic development of the child, give him a predisposition to rare diseases that originate precisely in the chaos of such genes. Some factors that cause infertility can be traced to early stages of development. Therefore, infertility is already a generational issue. It is therefore necessary to inform and alert to important factors, and ways of life, giving rise to emerging problems. PMID- 22040139 TI - Dynamic nuclear polarization-enhanced solid-state NMR of a 13C-labeled signal peptide bound to lipid-reconstituted Sec translocon. AB - Dynamic nuclear polarization (DNP) has made it possible to record 2D double quantum-filtered (DQF) solid-state NMR (ssNMR) spectra of a signal peptide bound to a lipid-reconstituted SecYEG translocon complex. The small quantity of peptide in the sample (~40 nmol) normally prohibits multidimensional ssNMR experiments. Such small amounts are not the exception, because for samples involving membrane proteins, most of the limited sample space is occupied by lipids. As a consequence, a conventional 2D DQF ssNMR spectrum with the sample used here would require many weeks if not months of measurement time. With the help of DNP, however, we were able to acquire such a 2D spectrum within 20 h. This development opens up new possibilities for membrane protein studies, particularly in the exploitation of high-resolution spectroscopy and the assignment of individual amino acid signals, in this case for a signal peptide bound to the translocon complex. PMID- 22040140 TI - Genotyping success of historical Eurasian lynx (Lynx lynx L.) samples. AB - Historical samples, like tanned hides and trophy skulls, can be extremely important for genetic studies of endangered or elusive species. Selection of a sampling protocol that is likely to provide sufficient amount and quality of DNA with a minimum damage to the original specimen is often critical for a success of the study. We investigated microsatellite genotyping success of DNA isolated from three different types of Eurasian lynx historical samples. We analysed a total of 20 microsatellite loci in 106 historical samples from the endangered Dinaric lynx population, established from re-introduction of three pairs of lynx in 1973 from Slovakian Carpathians. Of the three tested sample types, turbinal bone and septum from the nasal cavity of the trophy skulls had the lowest percentage of samples successfully genotyped for all 20 microsatellite loci. Footpad samples, collected using a cork drill, exhibited better results in polymerase chain reaction amplification and genotyping than samples of footpad epidermis cut with a scalpel. We report simple and efficient sampling protocols, which could be widely applied for future studies utilizing historical samples. PMID- 22040141 TI - Investigation of biomarkers of bile tolerance in Lactobacillus casei using comparative proteomics. AB - The identification of cell determinants involved in probiotic features is a challenge in current probiotic research. In this work, markers of bile tolerance in Lactobacillus casei were investigated using comparative proteomics. Six L. casei strains were classified on the basis of their ability to grow in the presence of bile salts in vitro. Constitutive differences between whole cell proteomes of the most tolerant strain (L. casei Rosell-215), the most sensitive one (L. casei ATCC 334), and a moderately tolerant strain (L. casei DN-114 001) were investigated. The ascertained subproteome was further studied for the six strains in both standard and bile stressing conditions. Focus was on proteins whose expression levels were correlated with observed levels of bile tolerance in vitro, particularly those previously reported to be involved in the bile tolerance process of lactobacilli. Analysis revealed that 12 proteins involved in membrane modification (NagA, NagB, and RmlC), cell protection and detoxification (ClpL and OpuA), as well as central metabolism (Eno, GndA, Pgm, Pta, Pyk, Rp1l, and ThRS) were likely to be key determinants of bile tolerance in L. casei and may serve as potential biomarkers for phenotyping or screening purposes. The approach used enabled the correlation of expression levels of particular proteins with a specific probiotic trait. PMID- 22040142 TI - The Wolinella succinogenes mcc gene cluster encodes an unconventional respiratory sulphite reduction system. AB - Assimilatory and dissimilatory sulphite reductions are key reactions in the biogeochemical sulphur cycle and several distinct sirohaem-containing sulphite reductases have been characterized. Here, we describe that the Epsilonproteobacterium Wolinella succinogenes is able to grow by sulphite respiration (yielding sulphide) with formate as electron donor. Sulphite is reduced by MccA, a prototypical member of an emerging new class of periplasmic cytochrome c sulphite reductases that, phylogenetically, belongs to a multihaem cytochrome c superfamily whose members play crucial roles in the global sulphur and nitrogen cycles. Within this family, MccA represents an unconventional octahaem cytochrome c containing a special haem c group that is bound via two cysteine residues arranged in a unique CX(15)CH haem c binding motif. The phenotypes of numerous W.succinogenes mutants producing MccA variants underlined the structural importance of this motif. Several open reading frames of the mcc gene cluster were individually inactivated and characterization of the corresponding mutants indicated that the predicted iron-sulphur protein MccC, the putative quinol dehydrogenase MccD (a member of the NrfD/PsrC family) as well as a peptidyl-prolyl cis-trans isomerase, MccB, are essential for sulphite respiration. MccA synthesis in W. succinogenes was found to be induced by sulphite (but not by thiosulphate or sulphide) and repressed in the presence of fumarate or nitrate. Based on the results, a sophisticated model of respiratory sulphite reduction by the Mcc system is presented. PMID- 22040143 TI - Electrochemiluminescent peptide nucleic acid-like monomers containing Ru(II) dipyridoquinoxaline and Ru(II)-dipyridophenazine complexes. AB - A series of Ru(II)-peptide nucleic acid (PNA)-like monomers, [Ru(bpy)(2)(dpq-L PNA-OH)](2+) (M1), [Ru(phen)(2)(dpq-L-PNA-OH)](2+) (M2), [Ru(bpy)(2)(dppz-L-PNA OH)](2+) (M3), and [Ru(phen)(2)(dppz-L-PNA-OH)](2+) (M4) (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, dpq-L-PNA-OH = 2-(N-(2-(((9H-fluoren-9 yl)methoxy)carbonylamino)ethyl)-6-(dipyrido[3,2-a:2',3'-c]phenazine-11 carboxamido)hexanamido)acetic acid, dppz-L-PNA-OH = 2-(N-(2-(((9H-fluoren-9-yl) methoxy)carbonylamino)ethyl)-6-(dipyrido[3,2-f:2',3'-h]quinoxaline-2 carboxamido)acetic acid) have been synthesized and characterized by IR and (1)H NMR spectroscopy, mass spectrometry, and elemental analysis. As is typical for Ru(II)-tris(diimine) complexes, acetonitrile solutions of these complexes (M1-M4) show MLCT transitions in the 443-455 nm region and emission maxima at 618, 613, 658, and 660 nm, respectively, upon photoexcitation at 450 nm. Changes in the ligand environment around the Ru(II) center are reflected in the luminescence and electrochemical response obtained from these monomers. The emission intensity and quantum yield for M1 and M2 were found to be higher than for M3 and M4. Electrochemical studies in acetonitrile show the Ru(II)-PNA monomers to undergo a one-electron redox process associated with Ru(II) to Ru(III) oxidation. A positive shift was observed in the reversible redox potentials for M1-M4 (962, 951, 936, and 938 mV, respectively, vs Fc(0/+) (Fc = ferrocene)) in comparison with [Ru(bpy)(3)](2+) (888 mV vs Fc(0/+)). The ability of the Ru(II)-PNA monomers to generate electrochemiluminescence (ECL) was assessed in acetonitrile solutions containing tripropylamine (TPA) as a coreactant. Intense ECL signals were observed with emission maxima for M1-M4 at 622, 616, 673, and 675 nm, respectively. At an applied potential sufficiently positive to oxidize the ruthenium center, the integrated intensity for ECL from the PNA monomers was found to vary in the order M1 (62%) > M3 (60%) > M4 (46%) > M2 (44%) with respect to [Ru(bpy)(3)](2+) (100%). These findings indicate that such Ru(II)-PNA bioconjugates could be investigated as multimodal labels for biosensing applications. PMID- 22040144 TI - Prevention of urinary tract infections in nursing homes: lack of evidence-based prescription? AB - BACKGROUND: Urinary tract infections (UTIs, including upper and lower symptomatic) are the most common infections in nursing homes and prevention may reduce patient suffering, antibiotic use and resistance. The spectre of agents used in preventing UTIs in nursing homes is scarcely documented and the aim of this study was to explore which agents are prescribed for this purpose. METHODS: We conducted a one-day, point-prevalence study in 44 Norwegian nursing homes during April-May 2006. Nursing home residents prescribed any agent for UTI prophylaxis were included. Information recorded was type of agent and dose, patient age and gender, together with nursing home characteristics. Appropriateness of prophylactic prescribing was evaluated with references to evidence in the literature and current national guidelines. RESULTS: The study included 1473 residents. 18% (n = 269) of the residents had at least one agent recorded as prophylaxis of UTI, varying between 0-50% among the nursing homes. Methenamine was used by 48% of residents prescribed prophylaxis, vitamin C by 32%, and cranberry products by 10%. Estrogens were used by 30% but only one third was for vaginal administration. Trimethoprim and nitrofurantoin were used as prophylaxis by 5% and 4%, respectively. CONCLUSIONS: The agents frequently prescribed to prevent UTIs in Norwegian nursing homes lack documented efficacy including methenamine and vitamin C. Recommended agents like trimethoprim, nitrofurantoin and vaginal estrogens are infrequently used. We conclude that prescribing of prophylactic agents for UTIs in nursing homes is not evidence based. PMID- 22040145 TI - Neurological disorders, virus persistence and hypomyelination in calves due to intra-uterine infections with bovine virus diarrhoea virus. AB - Summary The clinical and pathological findings after a natural intra-uterine infection with BVD-virus in a Friesian dairy herd are described. The virological and serological aspects will be discussed in a separate paper (30). In a period of 4 years, 11 calves were hum with the following nervous symptoms: more or less serious incoordination, tremor, oscillating nystagmus, and a negative blinking reflex. The pupillary and sucking reflexe's were normal. No ocular defects, such as lenticular opacity or retinal atrophy were observed. The first calf was born in 1979. Within 6 months the symptoms disappeared. After a normal conception and pregnancy this animal gave b(i)rth to 2 clinically normal calves in 1981 and 1982. The second calf died at the age of 2 months, due to an ulcerating enteritis. In 1980, again 8 calves with the same nervous symptoms were born within a period of 3 months. Two calves died at the age of 3 days and 5 weeks respectively; 2 calves were sold when 10 days and 3 weeks old; one calf did not improve and was necropsied at the age of 17 days. The remaining 3 calves showed only a slight hypermetria when examined after 6 months. At that time nystagmus was only visible with ophthalmoscopy. Two calves were slaughtered when 10 months old. The last one, a bull, proved to be sterile and was necropsied at the age of 1 1/2> year. A calf, born in 1981, recovered within a week and was necropsied at the age of 15 days. The last calf, born in 1982, did not improve at all and was necropsied at the age of 14 days. During these 4 years none of the other animals in the herd showed any symptoms due to an acute or chronic BVD-virus infection. At post mortem examination of 6 animals no macroscopically visible malformations were found. Hypomyelination and abnormal glial cells were evident in 5 cases, especially in the two youngest calves which did not show any improvement. One of them had an obvious thymic hypoplasia. The calf which recovered within a week showed only very slight changes. In one of the calves slaughtered at 10 months, inflammatory lesions were found in the brain. The diagnosis was confirmed by virological investigations. Clinically as well as pathologically there was a close resemblance to Border disease in lambs and congenital tremor in piglets after prenatal exposure to Hog cholera virus. PMID- 22040146 TI - Guide to Receptors and Channels (GRAC), 5th edition. AB - The Fifth Edition of the 'Guide to Receptors and Channels' is a compilation of the major pharmacological targets divided into seven sections: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside suggestions for further reading. Available alongside this publication is a portal at http://www.GuideToPharmacology.org which is produced in close association with NC-IUPHAR and allows free online access to the information presented in the Fifth Edition. PMID- 22040155 TI - Inequalities in utilisation of general practitioner and specialist services in 9 European countries. AB - BACKGROUND: The aim of this study is to describe the magnitude of educational inequalities in utilisation of general practitioner (GP) and specialist services in 9 European countries. In addition to West European countries, we have included 3 Eastern European countries: Hungary, Estonia and Latvia. To cover the gap in knowledge we pay a special attention to the magnitude of inequalities among patients with chronic conditions. METHODS: Data on the use of GP and specialist services were derived from national health surveys of Belgium, Estonia, France, Germany, Hungary, Ireland, Latvia, the Netherlands and Norway. For each country and education level we calculated the absolute prevalence and relative inequalities in utilisation of GP and specialist services. In order to account for the need for care, the results were adjusted by the measure of self-assessed health. RESULTS: People with lower education used GP services equally often in most countries (except Belgium and Germany) compared with those with a higher level of education. At the same time people with a higher education used specialist care services significantly more often in all countries, except in the Netherlands. The general pattern of educational inequalities in utilisation of specialist care was similar for both men and women. Inequalities in utilisation of specialist care were equally large in Eastern European and in Western European countries, except for Latvia where the inequalities were somewhat larger. Similarly, large inequalities were found in the utilisation of specialist care among patients with chronic diseases, diabetes, and hypertension. CONCLUSIONS: We found large inequalities in the utilisation of specialist care. These inequalities were not compensated by utilisation of GP services. Of particular concern is the presence of inequalities among patients with a high need for specialist care, such as those with chronic diseases. PMID- 22040156 TI - Ecological and evolutive implications of bacterial defences against predators. AB - Bacterial communities are often heavily consumed by microfaunal predators, such as protozoa and nematodes. Predation is an important cause of mortality and determines the structure and activity of microbial communities in both terrestrial and aquatic ecosystems, and bacteria evolved various defence mechanisms helping them to resist predation. In this review, I summarize known antipredator defence strategies and their regulation, and explore their importance for bacterial fitness in various environmental conditions, and their implications for bacterial evolution and diversification under predation pressure. I discuss how defence mechanisms affect competition and cooperation within bacterial communities. Finally I present some implications of bacterial defence mechanisms for ecosystem services provided by microbial communities, such as nutrient cycling, virulence and the biological control of plant diseases. PMID- 22040157 TI - The positive mental health instrument: development and validation of a culturally relevant scale in a multi-ethnic Asian population. AB - BACKGROUND: Instruments to measure mental health and well-being are largely developed and often used within Western populations and this compromises their validity in other cultures. A previous qualitative study in Singapore demonstrated the relevance of spiritual and religious practices to mental health, a dimension currently not included in exiting multi-dimensional measures. The objective of this study was to develop a self-administered measure that covers all key and culturally appropriate domains of mental health, which can be applied to compare levels of mental health across different age, gender and ethnic groups. We present the item reduction and validation of the Positive Mental Health (PMH) instrument in a community-based adult sample in Singapore. METHODS: Surveys were conducted among adult (21-65 years) residents belonging to Chinese, Malay and Indian ethnicities. Exploratory and confirmatory factor analysis (EFA, CFA) were conducted and items were reduced using item response theory tests (IRT). The final version of the PMH instrument was tested for internal consistency and criterion validity. Items were tested for differential item functioning (DIF) to check if items functioned in the same way across all subgroups. RESULTS: EFA and CFA identified six first-order factor structure (General coping, Personal growth and autonomy, Spirituality, Interpersonal skills, Emotional support, and Global affect) under one higher-order dimension of Positive Mental Health (RMSEA=0.05, CFI=0.96, TLI=0.96). A 47-item self administered multi-dimensional instrument with a six-point Likert response scale was constructed. The slope estimates and strength of the relation to the theta for all items in each six PMH subscales were high (range:1.39 to 5.69), suggesting good discrimination properties. The threshold estimates for the instrument ranged from -3.45 to 1.61 indicating that the instrument covers entire spectrums for the six dimensions. The instrument demonstrated high internal consistency and had significant and expected correlations with other well-being measures. Results confirmed absence of DIF. CONCLUSIONS: The PMH instrument is a reliable and valid instrument that can be used to measure and compare level of mental health across different age, gender and ethnic groups in Singapore. PMID- 22040158 TI - Theoretical studies on molecular and structures of mono- and binuclear chromium carbazole derivatives for optoelectronics. AB - Studies on the molecular geometries, electronic properties and second-order nonlinearities of a series of mono- and binuclear chromium carbazole complexes: (N-vinylcarbazole)Cr(CO)(3) (M1), (N-vinylcarbazole)Cr(CO)(2)PPh(3) (M2), (CO)(3)Cr(N-vinylcarbazole)Cr(CO)(3) (B1), and (CO)(3)Cr(N vinylcarbazole)Cr(CO)(2)PPh(3) (B2) were carried out, using the density functional theory (DFT) at the B3LYP//LanL2DZ/6-31G(d) level. The experimental singlet metal-to-ligand charge transfer ((1)MLCT) spectra of these complexes can also be well simulated and discussed by the time-dependent DFT (TDDFT) at the B3LYP//LanL2DZ/6-311+G(d) level associated with the polarizable continuum model (PCM). The computational results show that an unusual characteristic of chromium carbazole structures is explained in terms of interaction between frontier molecular orbitals of the metal and its ligands. The highest occupied molecular orbitals (HOMOs) of these complexes are composed of a set of distorted degenerated Cr 3d orbitals, whereas the lowest unoccupied molecular orbitals (LUMOs) are predominantly the N-vinylcarbazole ligand pi* orbitals. The HOMO-LUMO energy gaps decrease in the order NVC > M1 > B1 > M2 > B2. The considerable coupling between the carbazole and (CO)(3) in M1 creates an asymmetric environment about the chromium atom, leading to modest second-order responses. The PPh(3) ligand is acting as a donor which increases the donating strength of the d(pi) orbitals in chromium carbazole species, resulting in the large electronic asymmetry in M2. As for the binuclear chromium carbazole chromophores, a wide-range (1)MLCT band and large oscillator strength are found, allowing for the electronic interactions between two metal centers which can be modified by altering the ligand bound to the metals to induce peculiar asymmetry. Essentially, Cr(CO)(3) acceptor and Cr(CO)(2)PPh(3) donor units in B2 make significant contribution to the charge-transfer process or NLO responses via conventional push-pull chromophoric architecture. PMID- 22040159 TI - Validation of X-ray fluorescence spectrometry for determining osseous or dental origin of unknown material. AB - Forensic anthropological examinations typically involve the analysis of human skeletal remains, but in cases where samples are very small and/or physically compromised, it may first be necessary to determine whether the material is even osseous or dental in origin. X-ray fluorescence spectrometry (XRF) is a technique that reveals the elemental composition of materials and is hypothesized to have utility in such cases. XRF analysis was conducted on a variety of tissues and materials in unaltered and altered (damaged) states. With few exceptions, osseous and dental tissues in unaltered and altered conditions contained characteristic levels of calcium and phosphorus, while other materials did not. Materials could be accurately identified as osseous or dental in origin based on the calcium and phosphorus levels identified by XRF, and we therefore conclude that XRF analysis is a valid and effective means of determining osseous or dental origin of unknown material. PMID- 22040160 TI - 1-Dodecanethiol self-assembled monolayers on cobalt. AB - Cobalt and its alloys are used in a broad range of application fields. However, the use of this metal is especially limited by its strongly oxidizable nature. The use of alkanethiol self-assembled monolayers (SAMs) is a very efficient way to protect against such oxidation and/or to inhibit corrosion. This surface modification method has been particularly applied to oxidizable metals such as copper or nickel, yet the modification of cobalt surfaces by alkanethiol SAMs received limited attention up to now. In this work, we study the influence of parameters by which to control the self-assembly process of 1-dodecanethiol monolayers on cobalt: nature of the surface pretreatment, solvent, immersion time, and concentration. Each of these parameters has been optimized to obtain a densely packed and stable monolayer able to efficiently prevent the reoxidation of the modified cobalt substrates. The obtained monolayers were characterized by X-ray photoelectron spectroscopy (XPS), polarization modulation infrared reflection-absorption spectroscopy, and contact angle measurements. The stability of the optimized 1-dodecanethiol monolayer upon air exposure for 28 days has been confirmed by XPS. PMID- 22040161 TI - Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men. AB - With increasing evidence for faulty paternal contribution to reproduction, there has been a steady increase in studies highlighting an association between sperm DNA damage, failed/delayed fertilisation and aberrant embryo development. Owing to prevailing ambiguity, the aims of the study were to analyse the genetic integrity of the male gamete and then to understand its association with age, standard semen parameters, lifestyle and occupational factors. The study included 504 subjects, attending university infertility clinic for fertility evaluation and treatment. Semen characteristics were analysed by standard criteria; terminal deoxynucelotidyl transferase-mediated nick end-labelling assay was employed for DNA damage assessment. The average incidence of sperm DNA damage in patients with normozoospermic semen parameters was <10%. Patients with oligozoospermia, severe oligozoospermia, oligoasthenoteratospermia, asthenoteratozoospermia and necrozoospermia had significantly higher level of sperm DNA damage (P < 0.001). Patients above 40 years of age had significantly high levels of DNA damage (P < 0.001) compared with their counterparts. Patients with varicocele and a history of alcohol consumption had higher incidence of spermatozoa with DNA damage (P < 0.01). Poor sperm characteristics in the ejaculate are associated with increased sperm DNA damage. Age-related increase in sperm DNA damage and association of the same with varicocele and alcohol consumption are also demonstrated. PMID- 22040162 TI - A one-dimensional extremely covalent material: monatomic carbon linear chain. AB - Polyyne and cumulene of infinite length as the typical covalent one-dimensional (1D) monatomic linear chains of carbon have been demonstrated to be metallic and semiconductor (Eg = 1.859 eV), respectively, by first-principles calculations. Comparing with single-walled carbon nanotubes, the densities are evidently low and the thermodynamic properties are similar below room temperature but much different at the high temperature range. Polyyne possesses a Young's modulus as high as 1.304 TPa, which means it is even much stiffer than carbon nanotubes and to be the superlative strong 1D material along the axial direction. The Young's modulus of cumulene is estimated to be 760.78 GPa. In addition, polyyne is predicted to be as a one-dimensional electronic material with very high mobility. PMID- 22040163 TI - Receptor tyrosine kinases: from biology to pathology. AB - Receptor tyrosine kinases (RTKs) are transmembrane proteins involved in the control of fundamental cellular processes in metazoans. RTKs possess a general structure that includes an extracellular domain, a transmembrane domain and a highly conserved tyrosine kinase domain. RTKs are classified according to their variable extracellular ligand-binding domain. Studies of human RTK members have yielded a wealth of information elucidating their importance. Improper functioning of these enzymes due to mutations, mainly in the kinase domain, is often manifested in various human diseases and is known to be involved in several types of cancer. Here we summarize most of human RTKs, their cognate ligands, as well as related diseases and discuss the eventual use of certain RTKs as new therapeutic targets. PMID- 22040164 TI - Multifunctional encoded self-assembling protein nanofibrils as platform for high throughput and multiplexed detection of biomolecules. AB - A one-dimensional nanofibrillar array formed by the co-assembly of native and biotin-functionalized beta-amyloid (Abeta) peptide was developed for biomolecule sensing. With the presence of biotin moiety, a variety of biomolecular probes can be conjugated onto the nanofibrils, thus converting the protein assembly into a miniature biosensor. In this work, DNA probes were immobilized onto the fibril for the detection of cDNA sequences. The as-developed "DNA-nanoarray" achieved a detection limit at subattomole level (183 fM in 10 MUL). This highly sensitive, yet simple, assay requires a trace amount of sample consumption (<10 MUL) and is pretreatment-free. In addition, we reported the preparation of alternate segmented amyloid nanofibrils with multifunctionality. The fibrils hereby serve as an encoded template that can be visualized with various fluorescence labeling dyes for barcode recognition purpose, and, hence, multiplex detection of biomolecules was achieved. Regarding that each protein nanofibril represents a single detection platform, a large number of single fibrils simultaneously are monitored with the dual-color TIRFM in a high-throughput manner. PMID- 22040165 TI - Self-reported oral health, oral hygiene habits and dental service utilization among pregnant women in United Arab Emirates. AB - AIM: The aim of this study was to describe self-reported oral health, oral hygiene habits and frequency of visits to a dentist among pregnant women visiting maternity hospitals in the United Arab Emirates. MATERIAL AND METHODS: A cross sectional study was conducted, with anonymous structured questionnaires distributed to 800 pregnant women who were chosen at random from attendants of three maternity and child health centres from various geographical areas of UAE, during January-March 2010. RESULTS: The response rate was 93.7% (n = 750). Less than quarter of the participated pregnant women were in their first trimester. Almost a quarter (23.5%) of the women believed that they had periodontal problem currently, while 46.3% reported having carious teeth. More than 44% reported having dental pain, and about 40% women felt that her oral health was poor. About 60% reported having heard about the possible connection between pregnancy and the oral health. About 94% of the women were brushing their teeth at least once a day. More than half of the women (58.3%) visited the dentist during their most recent pregnancy, mostly for dental pain. CONCLUSIONS: A large proportion of the pregnant women in this study had oral health problems; however, more than 40% of those women had not visited a dentist during their pregnancy, and the majority of those utilized dental services when they had dental pain only. To provide better oral health care, more knowledge needs to be made available to the pregnant women and the medical community. PMID- 22040166 TI - Organic photocatalysts for the oxidation of pollutants and model compounds. PMID- 22040167 TI - Drug shortages--a critical challenge for the generic-drug market. PMID- 22040168 TI - Are elderly patients at increased risk of complications following pacemaker implantation? A meta-analysis of randomized trials. AB - BACKGROUND: Patients over the age of 75 represent more than half the recipients of permanent pacemakers. It is not known if they have a different risk of complications than younger patients. METHODS: Patient-level data were pooled from the CTOPP, UKPACE, and Danish pacing trials. These three randomized trials of pacing mode systematically captured early and late complications following pacemaker insertion. Early postimplant complications included lead dislodgement or loss of capture, cardiac perforation, pneumothorax, hematoma, infection, and death. Lead fracture was considered a late complication. RESULTS: A total of 4,814 patients were included in this analysis, with an average follow-up of 5.1 years. The average age was 76 years and 43% were female. Any early complication occurred in 5.1% of patients >=75 years of age compared to 3.4% of patients aged <75 years (P = 0.006). This was driven by an increased risk of pneumothorax (1.6% vs 0.8%, P = 0.07) and both atrial and ventricular lead dislodgement/loss of capture (2.0% vs 1.1%, P = 0.07). Early complications were higher in patients receiving atrial-based pacemakers in both age groups (<75 years: 4.6% vs 2.4%; >=75 years: 6.6% vs 3.7%); however, the relative risk was not influenced by age group. Older patients had a lower risk of lead fracture (3.6% vs 2.7%, P = 0.08). CONCLUSION: Elderly patients (>=75 years of age) are at increased risk of early postimplant complications but are at lower risk for lead fracture. PMID- 22040169 TI - Objectives of teaching direct ophthalmoscopy to medical students. AB - PURPOSE: To propose the objectives of undergraduate training in direct ophthalmoscopy (DO). METHOD: Narrative review of the literature on (i) opinions about the expected proficiency from students in DO, and (ii) estimates of its diagnostic value. RESULTS: (i) Authorities disagree on the proficiency in DO that they expect from students. Textbooks of physical diagnosis differ in their coverage of DO. Surveys have indicated that US physicians expect students to be able to detect optic nerve head abnormalities. The Association of American Medical Colleges expects students to perform ophthalmoscopic examination and describe observations. The International Council of Ophthalmology expects students to recognize also diabetic and hypertensive retinopathies. The Association of University Professors in Ophthalmology requires that students recognize papilloedema, cholesterol emboli, glaucomatous cupping and macular degeneration. (ii) There is evidence that DO, even by ophthalmologists, is inadequate for screening for glaucoma, diabetic and hypertensive retinopathies. Two studies have suggested a limited value of DO in detecting clinical emergencies. CONCLUSIONS: The evidence that DO, even by ophthalmologists, is sub optimal in detecting common abnormalities challenges existing the notions of training medical students. On pending the results of additional studies of the value of DO in detecting emergencies, we suggest that undergraduate teaching of DO should impart the following: (i) an ability to identify the red fundus reflex and optic disc; (ii) an ability to recognize signs of clinical emergencies in patients, mannequins or fundus photographs; and (iii) knowledge about, but not an ability to detect, other retinopathies. PMID- 22040171 TI - Mass spectrometric characterization of human N-acylethanolamine-hydrolyzing acid amidase. AB - N-Acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal enzyme that primarily degrades palmitoylethanolamine (PEA), a lipid amide that inhibits inflammatory responses. We developed a HEK293 cell line stably expressing the NAAA pro-enzyme (zymogen) and a single step chromatographic purification of the protein from the media. Matrix-assisted laser desorption/ionization time-of flight mass spectrometry MALDI-TOF MS analysis of the zymogen (47.7 kDa) treated with peptide-N-glycosidase F (PNGase F) identified 4 glycosylation sites, and acid cleavage of the zymogen into alpha- and beta-subunits (14.6 and 33.3 kDa) activated the enzyme. Size exclusion chromatography estimated the mass of the active enzyme as 45 +/- 3 kDa, suggesting formation of an alpha/beta heterodimer. MALDI-TOF MS fingerprinting covered more than 80% of the amino acid sequence, including the N-terminal peptides, and evidence for the lack of a disulfide bond between subunits. The significance of the cysteine residues was established by their selective alkylation resulting in almost complete loss of activity. The purified enzyme was kinetically characterized with PEA and a novel fluorogenic substrate, N-(4-methyl coumarin) palmitamide (PAMCA). The production of sufficient quantities of NAAA and a high throughput assay could be useful in discovering novel inhibitors and determining the structure and function of this enzyme. PMID- 22040172 TI - The alpha(2C)-Del322-325 adrenoceptor polymorphism and the occurrence of left ventricular hypertrophy in hypertensives. AB - OBJECTIVES: Sympathetic activation has a role in the development of left ventricular hypertrophy (LVH). The presynaptic alpha(2C)-adrenoceptor inhibits the release of norepinephrine from sympathetic nerve terminals in the heart. A deletion polymorphism in the alpha(2C)-adrenoceptor (alpha(2C)Del322-325) generates a hypofunctional alpha(2C)-adrenoceptor, which may result in chronic adrenergic signalling. This study aimed to investigate whether the alpha(2C)Del322-325 polymorphism was associated with an increased prevalence of LVH in patients with systemic hypertension. METHODS: Left ventricular mass was measured in 205 patients with systemic hypertension and 60 normal volunteers using a 1.5-T Philips MRI system. Genotyping was performed using a restriction fragment length polymorphism assay. RESULTS: No significant difference was observed between the distribution of the alpha(2C)Del322-325 genotypes in hypertensive patients with LVH compared with those without LVH. Adjusting for confounding variables the odds ratio (OR) of being ins/del for the alpha(2C)Del322-325 and having LVH was 0.49 (95% CI 0.14-1.69, p = 0.256). CONCLUSIONS: These observations suggest that there is little evidence for an association between alpha(2C)Del322-325 polymorphism and an increased prevalence of LVH in patients with systemic hypertension. PMID- 22040173 TI - Mechanism of NO photodissociation in photolabile manganese-NO complexes with pentadentate N5 ligands. AB - The Mn-nitrosyl complexes [Mn(PaPy(3))(NO)](ClO(4)) (1; PaPy(3)(-) = N,N-bis(2 pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide) and [Mn(PaPy(2)Q)(NO)](ClO(4)) (2, PaPy(2)Q(-) = N,N-bis(2-pyridylmethyl)amine-N ethyl-2-quinoline-2-carboxamide) show a remarkable photolability of the NO ligand upon irradiation of the complexes with UV-vis-NIR light [Eroy-Reveles, A. A.; Leung, Y.; Beavers, C. M.; Olmstead, M. M.; Mascharak, P. K. J. Am. Chem. Soc. 2008, 130, 4447]. Here we report detailed spectroscopic and theoretical studies on complexes 1 and 2 that provide key insight into the mechanism of NO photolabilization in these compounds. IR- and FT-Raman spectroscopy show N-O and Mn-NO stretching frequencies in the 1720-1750 and 630-650 cm(-1) range, respectively, for these Mn-nitrosyls. The latter value for nu(Mn-NO) is one of the highest transition-metal-NO stretching frequencies reported to this date, indicating that the Mn-NO bond is very strong in these complexes. The electronic structure of 1 and 2 is best described as Mn(I)-NO(+), where the Mn(I) center is in the diamagnetic low-spin state and the NO(+) ligand forms two very strong pi backbonds with the d(xz) and d(yz) orbitals of the metal. This explains the very strong Mn-NO bonds observed in these complexes, which even supersede the strengths of the Fe- and Ru-NO bonds in analogous (isoelectronic) Fe/Ru(II)-NO(+) complexes. Using time-dependent density functional theory (TD-DFT) calculations, we were able to assign the electronic spectra of 1 and 2, and to gain key insight into the mechanism of NO photorelease in these complexes. Upon irradiation in the UV region, NO is released because of the direct excitation of d(pi)_pi* -> pi*_d(pi) charge transfer (CT) states (direct mechanism), which is similar to analogous NO adducts of Ru(III) and Fe(III) complexes. These are transitions from the Mn-NO bonding (d(pi)_pi*) into the Mn-NO antibonding (pi*_d(pi)) orbitals within the Mn-NO pi backbond. Since these transitions lead to the population of Mn-NO antibonding orbitals, they promote the photorelease of NO. In the case of 1 and 2, further transitions with distinct d(pi)_pi* -> pi*_d(pi) CT character are observed in the 450-500 nm spectral range, again promoting photorelease of NO. This is confirmed by resonance Raman spectroscopy, showing strong resonance enhancement of the Mn-NO stretch at 450-500 nm excitation. The extraordinary photolability of the Mn-nitrosyls upon irradiation in the vis-NIR region is due to the presence of low-lying d(xy) -> pi*_d(pi) singlet and triplet excited states. These have zero oscillator strengths, but can be populated by initial excitation into d(xy) -> L(Py/Q_pi*) CT transitions between Mn and the coligand, followed by interconversion into the d(xy) -> pi*_d(pi) singlet excited states. These show strong spin-orbit coupling with the analogous d(xy) -> pi*_d(pi) triplet excited states, which promotes intersystem crossing. TD-DFT shows that the d(xy) -> pi*_d(pi) triplet excited states are indeed found at very low energy. These states are strongly Mn-NO antibonding in nature, and hence, promote dissociation of the NO ligand (indirect mechanism). The Mn-nitrosyls therefore show the long sought-after potential for easy tunability of the NO photorelease properties by simple changes in the coligand. PMID- 22040174 TI - Competition among Hfq-binding small RNAs in Escherichia coli. AB - A major class of small bacterial RNAs (sRNAs) regulate translation and mRNA stability by pairing with target mRNAs, dependent upon the RNA chaperone Hfq. Hfq, related to the Lsm/Sm families of splicing proteins, binds the sRNAs and stabilizes them in vivo and stimulates pairing with mRNAs in vitro. Although Hfq is abundant, the sRNAs, when induced, are similarly abundant. Therefore, Hfq may be limiting for sRNA function. We find that, when overexpressed, a number of sRNAs competed with endogenous sRNAs for binding to Hfq. This correlated with lower accumulation of the sRNAs (presumably a reflection of the loss of Hfq binding), and lower activity of the sRNAs in regulating gene expression. Hfq was limiting for both positive and negative regulation by the sRNAs. In addition, deletion of the gene for an expressed and particularly effective competitor sRNA improved the regulation of genes by other sRNAs, suggesting that Hfq is limiting during normal growth conditions. These results support the existence of a hierarchy of sRNA competition for Hfq, modulating the function of some sRNAs. PMID- 22040175 TI - Elacytarabine--lipid vector technology overcoming drug resistance in acute myeloid leukemia. AB - INTRODUCTION: Ara-C (cytarabine arabinoside) is a deoxycytidine analog that has an established role in the treatment of hematologic malignancies, especially acute myeloid leukemia. Resistance to ara-C occurs and impacts negatively on survival. To combat this, an elaidic acid ester of ara-C, called elacytarabine, has been developed. This novel agent is highly efficacious in cells with demonstrable resistance to the parent agent, including in solid tumor xenografts. AREAS COVERED: The mechanisms that account for the increased clinical activity of elacytarabine are discussed, including its ability to bypass the specialized transmembrane nucleoside transport system on which ara-C depends, its prolonged retention within the cell and its alternative effect on the cell cycle. The development and synthesis and pharmacokinetics are outlined, with emphasis on lipid vector technology. Ten clinical trials involving elacytarabine, either as monotherapy or part of a combination regimen, have been carried out in both solid tumor and hematologic malignancies. The efficacy and side effect profile results are summarized. EXPERT OPINION: Clinical trials in patients with hematological malignancies are reporting very encouraging efficacy results with an acceptable side effect profile. Elacytarabine has the potential to play an important role in the treatment of multiple malignancies in the future and results from an ongoing Phase III clinical trial are eagerly awaited. PMID- 22040176 TI - Nocardia transvalensis keratitis: an emerging pathology among travelers returning from Asia. AB - BACKGROUND: The incidence rate of Nocardia keratitis is increasing, with new species identified thanks to molecular methods. We herein report a case of Nocardia transvalensis keratitis, illustrating this emerging pathology among travellers returning from Asia. CASE PRESENTATION: A 23-year-old man presented with a 10-week history of ocular pain, redness, and blurred vision in his right eye following a projectile foreign body impacting the cornea while motor biking in Thailand. At presentation, a central epithelial defect with a central whitish stromal infiltrate associated with pinhead satellite infiltrates was observed. Identification with 16S rRNA PCR sequencing and microbiological culture of corneal scraping and revealed N. transvalensis as the causative organism. Treatment was initiated with intensive topical amikacin, oral ketoconazole and oral doxycycline. After a four-week treatment period, the corneal infiltrate decreased so that only a faint subepithelial opacity remained. CONCLUSION: Nocardia organisms should be suspected as the causative agent of any case of keratitis in travelers returning from Asia. With appropriate therapy, Nocardia keratitis resolves, resulting in good visual outcome. PMID- 22040177 TI - Synthesis of the butatriene C4 function: methodology and applications. PMID- 22040179 TI - Peer reviewers. PMID- 22040178 TI - Biophysical modeling to simulate the response to multisite left ventricular stimulation using a quadripolar pacing lead. AB - BACKGROUND: Response to cardiac resynchronization therapy (CRT) is reduced in patients with posterolateral scar. Multipolar pacing leads offer the ability to select desirable pacing sites and/or stimulate from multiple pacing sites concurrently using a single lead position. Despite this potential, the clinical evaluation and identification of metrics for optimization of multisite CRT (MCRT) has not been performed. METHODS: The efficacy of MCRT via a quadripolar lead with two left ventricular (LV) pacing sites in conjunction with right ventricular pacing was compared with single-site LV pacing using a coupled electromechanical biophysical model of the human heart with no, mild, or severe scar in the LV posterolateral wall. RESULT: The maximum dP/dt(max) improvement from baseline was 21%, 23%, and 21% for standard CRT versus 22%, 24%, and 25% for MCRT for no, mild, and severe scar, respectively. In the presence of severe scar, there was an incremental benefit of multisite versus standard CRT (25% vs 21%, 19% relative improvement in response). Minimizing total activation time (analogous to QRS duration) or minimizing the activation time of short-axis slices of the heart did not correlate with CRT response. The peak electrical activation wave area in the LV corresponded with CRT response with an R(2) value between 0.42 and 0.75. CONCLUSION: Biophysical modeling predicts that in the presence of posterolateral scar MCRT offers an improved response over conventional CRT. Maximizing the activation wave area in the LV had the most consistent correlation with CRT response, independent of pacing protocol, scar size, or lead location. PMID- 22040180 TI - Harmonic focus in total thyroidectomy plus level III-IV and VI dissection: a prospective randomized study. AB - The aim of this study was to compare operating time, postoperative outcomes, and surgical complications of total thyroidectomy plus level III-IV and VI dissection between the no-tie technique using the Harmonic Focus and classic suture ligation for hemostasis. Fifty-four patients underwent total thyroidectomy plus level III IV and VI dissection by classic suture ligation and 51 patients by the Harmonic Focus. There was obvious distinction as to the operating time between the Focus and classic group (102.8 and 150.1 minutes, respectively, P < 0.05). Drainage volume (202.7 +/- 187.0 mL vs 299.7 +/- 201.4 mL, P < 0.05) were significantly lower in the Focus group. Transient hypoparathyroidism had no statistically significant difference between the groups (17.6% vs 18.5%, P > 0 .05). No patient experienced nerve injury or permanent hypocalcemia. The use of Harmonic Focus for the control of thyroid vessels during thyroid surgery is reliable and safe. The device can offer extraordinary capabilities for delicate tissue grasping and dissection. PMID- 22040181 TI - Theoretical study of the structural properties of plutonium(IV) and (VI) complexes. AB - The structural properties of several plutonium(IV) and (VI) complexes have been examined in the gaseous and aqueous phases using Kohn-Sham density functional theory calculations with scalar relativistic effective core potentials and the polarizable continuum solvation model. The aquo and nitrate complexes of PuO(2)(2+) and Pu(4+) were considered in addition to the aquo-chloro complexes of PuO(2)(2+). The nitrate and chloro- complexes formed with triphenylphosphine oxide (TPPO) and tributylphosphate (TBP) respectively were also studied. The structural parameters of the plutonyl complexes were compared to their uranyl and neptunyl analogues. The bond lengths and vibrational frequencies of the plutonyl complexes can generally be computed with sufficient accuracy with the pure PBE density functional with shorter bond lengths being predicted by the B3LYP functional. The structural parameters of the [PuO(2)Cl(2)L(2)] systems formed with TPPO and TBP as well as the aqueous [PuO(2)Cl(2)(H(2)O)(3)] complex are matched to previous experimental results. Overall, the inclusion of ligands in the equatorial region results in significant changes in the stretching frequency of the plutonyl group. The structural features of the plutonyl (VI) systems are rather similar to those of their 5f(0) uranyl and 5f(1) neptunyl counterparts. For the Pu(IV) aquo and nitrate complexes, the average of the calculated Pu-OH(2) and Pu-O(nitrate) bond lengths are generally within 0.04 A of the reported experimental values. Overall Kohn-Sham DFT can be used successfully in predicting the structures of this diverse set of Pu(VI) and Pu(IV) complexes. PMID- 22040182 TI - Sensitivity of protein adsorption to architectural variations in a protein resistant polymer brush containing engineered nanoscale adhesive sites. AB - Patchy polymer brushes contain nanoscale (5-15 nm) adhesive elements, such as polymer coils or nanoparticles, embedded at their base at random positions on the surface. The competition between the brush's steric (protein resistant) repulsions and the attractions from the discrete adhesive elements provides a precise means to control bioadhesion. This differs from the classical approach, where functionality is placed on the brush's periphery. The current study demonstrates the impact of poly(etheylene glycol) (PEG) brush architecture and ionic strength on fibrinogen adsorption on brushes containing embedded poly-l lysine (PLL, 20K MW) coils or "patches". The consistent appearance of a fibrinogen adsorption threshold, a minimum loading of patches on the surface, below which protein adsorption does not occur, suggests multivalent protein capture: Adsorbing proteins simultaneously engage several patches. The surface composition (patch loading) at the threshold is extremely sensitive to the brush height and ionic strength, varying up to a factor of 5 in the surface loading of the PLL patches (~50% of the range of possible surfaces). Variations in ionic strength have a similar effect, with the smallest thresholds seen for the largest Debye lengths. While trends with brush height were the clearest and most dominant, consideration of the PEG loading within the brush or its persistence length did not reveal a critical brush parameter for the onset of adsorption. The lack of straightforward correlation on brush physics was likely a result of multivalent binding, (producing an additional dependence on patch loading), and might be resolved for univalent adsorption onto more strongly binding patches. While studies with similar brushes placed uniformly on a surface revealed that the PEG loading within the brush is the best indicator of protein resistance, the current results suggest that brush height is more important for patchy brushes. Likely the interactions producing brush extension normal to the interface act similarly to drive lateral tether extension to obstruct patches. PMID- 22040183 TI - Two opinions about one child--what's the clinician to do? PMID- 22040184 TI - When parent and teacher ratings don't agree: the Tracking Adolescents' Individual Lives Survey (TRAILS). AB - OBJECTIVES: A commonly encountered situation for evaluating clinicians is a history of significant problems in one setting with little or no difficulties in another. This study aims to describe this phenomenon and to examine its relations with other child and family characteristics. METHOD: A total of 1,730 children (mean age 11.05 years) was studied from the first wave of the Tracking Adolescents' Individual Lives Survey (TRAILS), a large population-based study of Dutch youth. Parent and teacher ratings of aggression, rule breaking, inattention, and hyperactivity were obtained. Children were assigned to groups according to the presence of clinically relevant problems at home only, at school only, or in both settings. The rate of setting specific problems was calculated and comparisons between groups were made. RESULTS: Setting specific, especially home-specific, problems were quite common. Among children whom parents rated as having at least borderline-clinical problems, teachers reported clear or very clear behaviors at school at the following rates: aggression (22%), rule breaking (12.5%), inattention (55%), and hyperactivity/impulsivity (33%). Compared with the school-specific group, the home-specific group contained a significantly higher percentage of girls with regard to inattention or hyperactivity and a significantly lower percentage of girls with regards to rule breaking. Logistic regression analyses revealed that home- versus school-specific problems were related to sex, child effortful control, and parental stress. CONCLUSION: Externalizing problems are frequently encountered only in one setting between home and school and are related to sex, child effortful control, and parental stress. PMID- 22040185 TI - Diagnostic implications of informant disagreement for manic symptoms. AB - OBJECTIVE: This study examines diagnoses that occur in an outpatient sample when both parent and teacher endorse significant manic symptoms and when only a parent observes them. We hypothesized that the diagnosis of mania/bipolar (BP) disorder would occur when there is parent/teacher concordance on high mania symptom scores. METHODS: Subjects were 911 5-18-year-old psychiatrically diagnosed youths with caregiver and teacher completed Child Mania Rating Scales (CMRSs) and Achenbach parent and teacher forms. Parent-teacher concordance on the CMRS was defined as both informants >=75 percentile on the CMRS; discordance on the CMRS was defined as parent >=75 percentile and teacher <=25 percentile. Logistic regression examined factors associated with a child's parent and teacher ratings concordant for high CMRS total scores. RESULTS: Correlation between parent CMRS (CMRS-P) and teacher CMRS (CMRS-T) scores was r=0.27 (p<0.000). Correlation between the CMRS-P and the Child Behavior Checklist "bipolar/dysregulation" phenotype was r=0.757 and between the CMRS-T and Teacher Report Form "bipolar/dysregulation" phenotype was r=0.786. A total of 66 (7.3%) of the 911 children were diagnosed with BP I (n=20) or II (n=3) or BP disorder not otherwise specified (BPNOS, n=43). If the CMRS-P score was >=15, 14.7% (vs. 4.4%) had any BP (odds ratio: 3.6; 95% confidence interval: 2.1, 6.2). Teacher agreement or disagreement did not add to diagnostic accuracy for students with BP I or II. BPNOS was more common in children with concordant high CMRS-P and CMRS-T ratings (10.5% vs. 4.8%) but the difference was not statistically significant. However, logistic regression indicated 10-fold greater odds of both parents and teachers, providing high CMRS ratings among children who were diagnosed with externalizing disorders (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, or any combination of these). Children with internalizing disorders (anxiety and depressive disorders) were 3.7 times more likely to have discordant CMRS-P/CMRS-T ratings. CONCLUSION: Parent and teacher concordance on high mania rating scale scores was most associated with externalizing disorders, and discordance was most associated with internalizing disorders. PMID- 22040186 TI - Informants are not all equal: predictors and correlates of clinician judgments about caregiver and youth credibility. AB - OBJECTIVE: The objectives of this study were to examine how often clinicians judged youths or caregivers to not be credible informants, to identify the associated features of youth or caregiver credibility, and to examine credibility's impact on the validity of mood and behavior checklists. BACKGROUND: Clinicians often have the experience of talking to a parent or a youth and judging that the credibility of the information offered is unusually poor. Little is known about the correlates of poor credibility or about the extent to which credibility changes the validity of commonly used checklists. METHODS: Interviewers rated the credibility of 646 youths aged 5-18 and their primary caregivers after completing a Kiddie Schedule for Affective Disorders and Schizophrenia. Ratings and diagnoses were blind to the behavior checklists completed by caregivers, youths, and teachers. A subset of youths also had intelligent quotient tests and behavioral observations available. RESULTS: Caregivers were perceived as more credible on average than youths, though this dropped sharply with adolescents. Caregiver credibility was higher for better functioning families, more credible youths, younger youths, and more educated caregivers; it was unrelated to caregiver mood symptoms or being the mother. Youth credibility was strongly connected to age, cognitive ability, caregiver credibility, and independent observations of youth behavior. Credibility ratings markedly altered the validity of checklists compared with interview ratings, diagnoses, or cross-informant criteria. CONCLUSION: Clinicians' judgments about informant credibility are associated with different characteristics for youths versus caregivers, though youth age is important to both. Credibility affects the validity of information from checklists measured against several different independent criteria. PMID- 22040187 TI - Informant discrepancies in clinical reports of youths and interviewers' impressions of the reliability of informants. AB - OBJECTIVE: In this study the authors examined whether discrepancies between parent and youth reports of the youth's emotional and behavioral functioning are related to interviewers' reliability ratings of parents and youths. METHODS: In a consecutive case series analysis of 328 parents and youths aged 11-17 years, parents and youths provided reports of youth emotional and behavioral functioning and participated in structured clinical interviews. At the conclusion of the interviews, interviewers rated the reliability of informants. Interviewers rated youths' clinical severity and parents and youths provided information on youth demographics. Nominal logistic regressions tested patterns of discrepancies between parent and youth reports (i.e., which informant consistently reported greater degrees of youth emotional and behavioral concerns than the other) as predictors of interviewers' ratings of the reliability of parents and youths. All analyses controlled for variance explained by youth demographics and youth severity. RESULTS: When parents reported greater degrees of youth emotional and behavioral concerns than youths self-reported, interviewers were likely to rate the youth as an unreliable informant, and were unlikely to rate the youth as an unreliable informant when parents reported less concerns than youths self reported. However, interviewers' ratings of parents' reliability did not relate to the discrepancies between reports, regardless of which informant reported greater degrees of youth concerns. CONCLUSIONS: Prior research indicates that informant discrepancies potentially reveal important information of youths' emotional and behavioral concerns, such as the settings in which youths express these concerns. Yet, when parents and youths disagree in their clinical reports of the youth's functioning, this relates to whether a clinical interviewer views the youth as a reliable informant of their own functioning. To increase the cost effectiveness and clinical utility of multi-informant clinical evaluations, practitioners and researchers should anticipate informant discrepancies and predict what they may represent before conducting clinical evaluations. PMID- 22040188 TI - Is caregiver-adolescent disagreement due to differences in thresholds for reporting manic symptoms? AB - INTRODUCTION: Cross-informant disagreement is common and results in different interpretations of a youth's behavior. Theoretical explanations for discrepancies typically rely on scale level analyses. This article explores whether caregivers and adolescents differ in when they notice and report symptoms of youth mania depending on the severity of overall manic disturbance. METHOD: Participants were 459 adolescent-caregiver pairs recruited at either a community mental health center or an academic medical center. Adolescents were most likely to have a primary diagnosis of unipolar depression (37%) or attention-deficit/hyperactivity disorder/disruptive behavior disorder (36%). Nineteen percent of adolescents received a bipolar spectrum disorder diagnosis (4% bipolar I and 15% bipolar II, cyclothymia, or bipolar not otherwise specificed). Caregivers were primarily biological mothers (74%) or grandparents (8%). Adolescents and caregivers independently completed the Mood Disorder Questionnaire (MDQ) about the adolescent. RESULTS: Item response theory analyses of the entire sample indicated that in general, both caregivers and adolescents reserved endorsement of mania symptoms for the most severely ill half of participants. Comparisons of caregiver and adolescent report of symptoms on the MDQ indicated two significant differences. Caregivers were more likely to report irritability at significantly lower severity of mania than adolescents. Adolescents endorsed only increased energy or hyperactivity at lower severities than caregivers. CONCLUSIONS: Adolescents and caregivers will have different concerns and might report different symptoms consistent with whom the symptom impacts first. Caregivers are more likely to report behaviors such as irritability, whereas adolescents are more likely to report subjective feelings such as feeling more energetic or more hyperactive. PMID- 22040189 TI - Neuropsychological outcomes across the day in children with attention deficit/hyperactivity disorder treated with atomoxetine: results from a placebo controlled study using a computer-based continuous performance test combined with an infra-red motion-tracking device. AB - The effect of atomoxetine (ATX) on executive function has been assessed by means of questionnaires only. The aim of this study was therefore to evaluate the efficacy of ATX using standard variables of a computer-based continuous performance test (cb-CPT) combined with an infra-red motion-tracking device at different times of the day. One hundred twenty-eight girls and boys aged 6 to 12 years with a diagnosis of ADHD according to DSM-IV-TR criteria were randomized in the study. The primary efficacy measures were the q-scores of the cb-CPT combined with an infra-red motion-tracking device. The test comprises 13 neuropsychological variables that can be taken to reflect hyperactivity, inattention, or impulsivity. One hundred five patients completed the study (ATX group: n=54; placebo group: n=51). ATX (target dose 1.2 mg/kg/day) over 8 weeks was significantly superior to placebo in reducing hyperactivity, inattention, and impulsivity as measured by q-scores of 10 primary variables of the cb-CPT. Both groups of patients showed a circadian pattern of neuropsychological outcomes across the day as reflected by the cb-CPT combined with an infra-red motion tracking device. In summary, this study demonstrated a positive effect of ATX on some aspects of executive function, inhibitory control, and hyperactivity compared with placebo. PMID- 22040190 TI - Subjective effects, misuse, and adverse effects of osmotic-release methylphenidate treatment in adolescent substance abusers with attention deficit/hyperactivity disorder. AB - OBJECTIVE: Psychostimulants are effective treatments for attention deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD. METHOD: Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (13-18) with at least one non-nicotine SUD and one with 255 adult smokers (18-55), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs). RESULTS: Euphoric effects and misuse/diversion of OROS MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults. CONCLUSIONS: With good monitoring, and in the context of substance abuse treatment, OROS-MPH can be safely used in adolescents with an SUD despite non-abstinence. PMID- 22040191 TI - Impulsivity in adolescents with bipolar disorder and/or attention deficit/hyperactivity disorder and healthy controls as measured by the Barratt Impulsiveness Scale. AB - OBJECTIVE: To compare the type and degree of impulsivity among adolescents with bipolar disorder (BD), adolescents with attention-deficit/hyperactivity disorder (ADHD), and healthy comparison subjects using the Barratt Impulsiveness Scale, Version 11 (BIS-11). METHODS: Manic adolescents with BD (n=31), adolescents with ADHD (n=30), and healthy subjects (n=25) completed the BIS-11, a 30-item, self report scale with three subscales (cognitive, motor, and nonplanning). The BIS-11 total and subscale scores were compared among groups. We also examined associations among the BIS-11, Young Mania Rating Scale and co-occurring disruptive behavioral disorders (DBDs) within the BD group. RESULTS: Total and each subscale scores were significantly higher for the BD group than for the healthy controls (p<0.05). The total scores and the cognitive and motor subscale scores were significantly higher for the ADHD group than for the healthy control group (p<0.05). However, there was no statistically significant difference between the nonplanning subscale scores of the ADHD group and the healthy control group (p>0.05). There were no significant differences between the BD and ADHD groups or between the BD groups with and without ADHD. The BD patients with DBDs (i.e., oppositional defiant disorder or conduct disorder) scored significantly higher on the motor subscale than did BD patients without DBDs. There were no statistically significant associations between the Young Mania Rating Scale and BIS-11 scores within the BD group. CONCLUSION: Our findings suggest that impulsivity is elevated in adolescents with BD as well as adolescents with ADHD, except for nonplanning impulsivity, which was not significantly different between adolescents with ADHD and the healthy comparison group. This may suggest that nonplanning impulsivity is relatively specific to adolescents with BD. Additionally, our data indicate that elevations in impulsivity, as measured by the BIS-11, may be independent of symptoms severity and, therefore, may be a stable, trait-related component of BD. PMID- 22040192 TI - A randomized controlled trial of sertraline to prevent posttraumatic stress disorder in burned children. AB - BACKGROUND: This study evaluated the potential benefits of a centrally acting selective serotonin reuptake inhibitor, sertraline, versus placebo for prevention of symptoms of posttraumatic stress disorder (PTSD) and depression in burned children. This is the first controlled investigation based on our review of the early use of a medication to prevent PTSD in children. METHODS: Twenty-six children aged 6-20 were assessed in a 24-week double-blind placebo-controlled design. Each child received either flexibly dosed sertraline between 25-150 mg/day or placebo. At each reassessment, information was collected in compliance with the study medication, parental assessment of the child's symptomatology and functioning, and the child's self-report of symptomatology. The protocol was approved by the Human Studies Committees of Massachusetts General Hospital and Shriners Hospitals for Children. RESULTS: The final sample was 17 subjects who received sertraline versus 9 placebo control subjects matched for age, severity of injury, and type of hospitalization. There was no significant difference in change from baseline with child-reported symptoms; however, the sertraline group demonstrated a greater decrease in parent-reported symptoms over 8 weeks (-4.1 vs. -0.5, p=0.005), over 12 weeks (-4.4 vs. -1.2, p=.008), and over 24 weeks ( 4.0 vs. -0.2, p=0.017). CONCLUSIONS: Sertraline was a safe drug, and it was somewhat more effective in preventing PTSD symptoms than placebo according to parent report but not child report. Based on this study, sertraline may prevent the emergence of PTSD symptoms in children. PMID- 22040195 TI - Drug-induced movement disorders and Syndenham's chorea in an antipsychotic treated young child. PMID- 22040193 TI - Preliminary findings regarding proinflammatory markers and brain-derived neurotrophic factor among adolescents with bipolar spectrum disorders. AB - Mood symptoms in adult bipolar disorder are associated with increased proinflammatory markers and decreased brain-derived neurotrophic factor (BDNF). We examined serum interleukin-6, high-sensitivity C-reactive protein (hsCRP), and BDNF among 30 bipolar disorder adolescents. Hypomanic/manic symptoms were positively associated with hsCRP. BDNF levels were negatively associated with interleukin-6. Forty percent had cardiovascular high-risk hsCRP levels. Larger longitudinal studies are warranted. PMID- 22040196 TI - Paliperidone palmitate in a child with autistic disorder. PMID- 22040197 TI - Methylphenidate transdermal system in preschool children with attention deficit/hyperactivity disorder. PMID- 22040198 TI - Biperiden-induced delirium in an adolescent patient. PMID- 22040199 TI - The configuration of cervical spinous processes in black and white South African skeletal samples. AB - The present study investigates the frequency of bifidity/nonbifidity in the black and white South African populations. Four-hundred skeletons of known race, sex, and tribal group were examined. Spinous processes were classified as bifid (bifurcate and cleft subtypes) and nonbifid (obtuse, pediculate, acinate, and clavate subtypes). Statistical analysis using the chi-squared probability test (p < 0.05) was carried out. Bifid spinous processes were present significantly more frequently in the white sample (58.9%) than in the black (31.6%). A bifid spinous process occurred most commonly in C2 (89%) followed by C5 (83%), C4 (79%), C3 (59.4%), and C6 (41.7%) in the white sample. A similar order of decrease in bifidity occurred in the black sample. C2 most commonly displayed the bifurcate subtype of spinous process, while the clavate subtype of nonbifid spinous process was the most common in both populations. The significantly higher frequency of bifidity in the white South African sample when compared to the black sample may suggest a population difference. PMID- 22040200 TI - Improvement of photon extraction efficiency of GaN-based LED using micro and nano complex polymer structures. AB - A micro- and nanoscale complex structure made of a high refractive index polymer (n = 2.08) was formed on the ITO electrode layer of an edge-emitting type GaN blue light-emitting diode (LED), in order to improve the photon extraction efficiency by suppressing total internal reflection of photons. The nanoimprint lithography process was used to form the micro- and nanoscale complex structures, using a polymer resin with dispersed TiO2 nano-particles as an imprint resin. Plasma processing, such as reactive ion etching, was used to form the micro- and nano-scale complex structure; thus, plasma-induced damage to the LED device can be avoided. Due to the high refractive index polymeric micro- and nanostructure on the ITO layer, the electroluminescence emission was increased up to 20%, compared to an identical LED that was grown on a patterned sapphire substrate to improve photon extraction efficiency. PMID- 22040201 TI - Breast cancer misclassification: a major obstacle to treatment? PMID- 22040202 TI - Missed opportunities for chronic disease prevention after breast cancer. PMID- 22040203 TI - Can ovarian reserve assessment predict fertility following breast cancer treatment? PMID- 22040205 TI - Mammographic screening: keeping women alive. AB - Evaluation of: Tabar L, Vitak B, Chen TH et al. Swedish Two-County Trial: impact of mammographic screening on breast cancer mortality during 3 decades. Radiology 260(3), 658-663 (2011). In the 1980s, the periodic invitation of women aged 40-69 years for mammographic screening in the Swedish Two-County Trial showed a strong 30% reduction in breast cancer mortality. The result of 2-3-yearly mammographic examinations has persisted throughout the long follow-up of three decades. Through the richness of the collected and verified data, the trial has also demonstrated a substantial and absolute reduction in mortality risk. For each 414 women screened for 7 years (approximately four screening examinations), one breast cancer death was prevented. Transferring these outcomes to, for example, the national program of the UK, for every 1000 women aged 47-73 years attending the 3-yearly screenings (nine screening examinations) at least five to seven breast cancer deaths would be prevented. In recent follow-up papers by the Swedish trial group, the major human cost of screening (false-positive outcome, occurrence of interval cancer, overdiagnosis and radiation exposure) were judged to be in balance with the accurately demonstrated mortality benefit. PMID- 22040206 TI - Preservation of ovarian function and minimizing premature ovarian failure during chemotherapy using gonadotropin-releasing hormone analogs. AB - Evaluation of: Del Mastro L, Boni L, Michelotti A et al. Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA 306(3), 269-276 (2011). This study is a randomized, open label, Phase III trial, conducted in 16 Italian centers that enrolled 281 patients between 2003 and 2008. The recruited patients were prospectively and randomly allocated to either chemotherapy alone or combined with monthly triptorelin gonadotropin-releasing hormone analog, started before chemotherapy and repeated every month throughout chemotherapy. The clinical and tumor characteristics of the patients in the control or treatment groups were similar. A total of 12 months after ending chemotherapy, the premature ovarian failure rate was 25.9% in the chemotherapy-alone group versus 8.9% in the chemotherapy and gonadotropin-releasing hormone analog group, an absolute difference of -17% (95% CI: -26 to -7.9%; p < 0.001). The odds ratio for treatment-induced premature ovarian failure was 0.28 (95% CI: 0.14-0.59; p < 0.001). The authors concluded that use of gonadotropin-releasing hormone analog chemotherapy in premenopausal breast cancer patients can significantly reduce the occurrence of chemotherapy induced early menopause. PMID- 22040207 TI - Reducing excessive gestational weight gain: lessons from the weight control literature and avenues for future research. AB - Excessive gestational weight gain is a prevalent problem and an independent predictor of future obesity in both mothers and offspring. Intervention research to prevent excessive gestational weight gain is still in its infancy but results to date have been quite modest. Research in weight control outside of pregnancy over the past 30 years has been more robust and identified several key components of effective programs, including use of caloric restriction, daily diet self monitoring, self-weighing, behavior therapy and ongoing patient-provider contact. The aim of this article is to summarize intervention components shown to be effective in promoting successful weight control outside of pregnancy and explore potential applications in pregnancy. Available evidence suggests that the strategies shown to be effective for weight control outside of pregnancy may also promote better weight control in pregnancy, but several lines for future investigation remain. PMID- 22040208 TI - Bipolar disorder differences between genders: special considerations for women. AB - The objective of this article is to review clinical differences between men and women with bipolar disorder. The secondary objective is to analyze the differences in adherence to medication between genders. Men usually present with manic episodes and have comorbid drug abuse, while women usually present with major depressive episode, the onset is often later, comorbidity of physical pathology is common and adherence to medication is greater than in men. In women who have an earlier onset of the illness and are single, the risk of nonadherence is higher than in other groups of women. There are two time periods that are very important in women: pregnancy and postpartum. Both are critical periods and a relapse or recurrence of symptoms at either stage can have serious consequences for the woman and/or her baby. In addition, the effect of medication on the fetus is unclear. In conclusion, there is a clear need for more studies on gender differences in bipolar disorder and how to improve adherence to treatment. Moreover, a better understanding of how to treat women with bipolar disorder during pregnancy and lactation will undoubtedly lead to improved outcomes for both the mother and her child. PMID- 22040209 TI - Ethnic differences in breast cancer survival: status and determinants. AB - Ethnic differences in breast cancer survival have been a long-standing concern. The objective of this article is to present relevant studies for all major US racial/ethnic groups including African-Americans, Latinos, Native Americans, Japanese-Americans and Native Hawaiians, and to discuss underlying causes of disparity. In comparison to Caucasian women, African-American women continue to experience the poorest breast cancer-specific survival of all ethnic groups in the USA. The prognosis for Latinos, Native Hawaiians and Native Americans is intermediate, better than for African-Americans but not as good as for Caucasians, whereas Japanese-American women tend to have better outcomes. The following possible contributors to the observed differences are discussed in detail: unfavorable distribution of stage at diagnosis due to low screening rates, limited access to care and treatment, tumor type, comorbidities, socioeconomic status, obesity and physical activity. PMID- 22040210 TI - Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options. AB - Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry based measurements of bone mineral density. However, within the last 20 years, biochemical markers of bone turnover have been implemented to a larger degree, and especially within the field of drug development. Numerous clinical studies have underscored that the markers have promise in terms of predicting patients at high risk of losing bone, future fracture events and importantly also the fracture efficacy of drugs in development. Furthermore, while classical methods often require years to monitor the changes, the bone turnover markers do so within a shorter time span. The aims of this article are to provide an update on the different biochemical markers of bone turnover, and to give an overview of their applications in epidemiological and clinical research especially in women. The main emphasis will be on their utility in clinical trials testing the efficacy of drugs for the treatment of osteoporosis, and their ability to supplement bone mass measurements. Finally, recent evidence suggests that biochemical markers may provide information on bone age that may indirectly relate to bone quality, and this is discussed together with future possibilities for measuring bone quality using bone turnover markers. In summary, a more targeted use of biomarkers could assist in the identification of high-risk patients, the process of drug discovery and monitoring of the efficacy of osteoporosis treatment in clinical settings. PMID- 22040211 TI - Opinions and expectations of women in the treatment of cervical and uterine cancer in Spain. AB - AIM: To know the experiences, needs and expectations of women in the treatment of cervical and uterine cancer in the Andalusian Health Service. METHODS: Focus groups and in-depth interviews with women being treated for cervical-uterine cancer within the Andalusian Health Service. Analysis with Nudist Vivo 1.0 (QSR International Pty Ltd, Doncaster, Victoria, Australia). RESULTS: The needs and expectations detected were: coherence in the promotion strategies and the presence of a proactive approach by health professionals, availability of comprehensive information and understanding, possibility of expressing to health professionals one's doubts and fears, and of participation in decision-making, technical quality, humane treatment and continuity of care and attention to psychosocial aspects. CONCLUSION: The knowledge of women in the treatment of cancer of the cervix and uterus plays a crucial part in improving the delivery of these services. PMID- 22040212 TI - Association between socioeconomic position in earlier and later life and age at natural menopause: Estudo Pro-Saude, Brazil. AB - This study was based on a prospective cohort of university staff in Rio de Janeiro, Brazil (the Estudo Pro-Saude). In this article the association between socioeconomic position (SEP) earlier and later in life and age at menopause is investigated. The main indicators investigated were for earlier SEP: mother's and father's schooling; stature; leg and trunk length. For later SEP they were: schooling; home and/or car ownership. Median age at menopause was estimated and survival curves were generated by the Kaplan-Meier method, while the association between indicators of SEP and age at menopause was explored by means of Cox semiparametric models. Associations were found between earlier SEP - represented by trunk length - and earlier menopause and between later SEP - represented by the indicator 'present schooling' - and earlier menopause. The association between earlier and later SEP was confirmed. Adverse situations over the life course can impact age at menopause and related health outcomes. PMID- 22040214 TI - Long-term medical utilization following ventilator-associated pneumonia in acute stroke and traumatic brain injury patients: a case-control study. AB - BACKGROUND: The economic burden of ventilator-associated pneumonia (VAP) during the index hospitalization has been confirmed in previous studies. However, the long-term economic impact is still unclear. The aim of this study is to examine the effect of VAP on medical utilization in the long term. METHODS: This is a retrospective case-control study. Study subjects were patients experiencing their first traumatic brain injury, acute hemorrhagic stroke, or acute ischemic stroke during 2004. All subjects underwent endotracheal intubation in the emergency room (ER) on the day of admission or the day before admission, were transferred to the intensive care unit (ICU) and were mechanically ventilated for 48 hours or more. A total of 943 patients who developed VAP were included as the case group, and each was matched with two control patients without VAP by age ( +/- 2 years), gender, diagnosis, date of admission ( +/- 1 month) and hospital size, resulting in a total of 2,802 patients in the study. Using robust regression and Poisson regression models we examined the effect of VAP on medical utilization including hospitalization expenses, outpatient expenses, total medical expenses, number of ER visits, number of readmissions, number of hospitalization days and number of ICU days, during the index hospitalization and during the following 2-year period. RESULTS: Patients in the VAP group had higher hospitalization expenses, longer length of stay in hospital and in ICU, and a greater number of readmissions than the control group patients. CONCLUSIONS: VAP has a significant impact on medical expenses and utilization, both during the index hospitalization during which VAP developed and in the longer term. PMID- 22040215 TI - Cultural issues in child maltreatment. AB - AIMS: Waves of immigration from the latter half of the 20th century have changed the cultural and ethnic mix of major regions of the world. Dynamic multicultural societies now are a reality across the Western world. The relationship and influence of these diverse cultures to the understanding and identification of child abuse and neglect is challenging and complex. Health professionals working with children from culturally and linguistically diverse groups often find themselves with the challenge of exploring and resolving the tension between definitions of harm in child protection practice and various cultural and child rearing practices. In this paper, we set out ways of thinking about the influence of culture when approaching and dealing with the suspicion of child maltreatment. METHODS: We will explore how culture shapes the experiences of childhood, child rearing practices, and identify common barriers in working with children and families from culturally diverse backgrounds when presenting with child maltreatment. We will use case examples from Europe and Australia to illustrate the real life challenges of working in the area of child maltreatment across cultures. We will review the scientific literature exploring the nexus between culture and child maltreatment, identifying the gaps in the literature and highlight areas for future research. RESULTS: We suggest a model for dealing with cultural issues in child maltreatment that is culturally competent and respectful. CONCLUSIONS: The model for cultural competency in child health and child protective services incorporates four domains for advocacy and action - individual, professional, organisational and systemic. PMID- 22040216 TI - Mechanisms of ellipticine-mediated resistance in UKF-NB-4 neuroblastoma cells. AB - Most high-risk neuroblastomas develop resistance to cytostatics and therefore there is a need to develop new drugs. In previous studies, we found that ellipticine induces apoptosis in human neuroblastoma cells. We also investigated whether ellipticine was able to induce resistance in the UKF-NB-4 neuroblastoma line and concluded that it may be possible after long-term treatment with increasing concentrations of ellipticine. The aim of the present study was to investigate the mechanisms responsible for ellipticine resistance. To elucidate the mechanisms involved, we used the ellipticine-resistant subline UKF-NB-4(ELLI) and performed comparative genomic hybridization, multicolor and interphase FISH, expression microarray, real-time RT-PCR, flow cytometry and western blotting analysis of proteins. On the basis of our results, it appears that ellipticine resistance in neuroblastoma is caused by a combination of overexpression of Bcl 2, efflux or degradation of the drug and downregulation of topoisomerases. Other mechanisms, such as upregulation of enzymes involved in oxidative phosphorylation, cellular respiration, V-ATPases, aerobic respiration or spermine synthetase, as well as reduced growth rate, may also be involved. Some changes are expressed at the DNA level, including gains, amplifications or deletions. The present study demonstrates that resistance to ellipticine is caused by a combination of mechanisms. PMID- 22040217 TI - Novel and recurrent JAG1 mutations in patients with tetralogy of Fallot. PMID- 22040218 TI - Diagnostic accuracy of non-invasive prenatal sex determination: a large-scale study. PMID- 22040219 TI - A GPHN point mutation leading to molybdenum cofactor deficiency. PMID- 22040220 TI - Pitt-Hopkins syndrome should be in the differential diagnosis for males presenting with an ATR-X phenotype. PMID- 22040221 TI - Mental health literacy: empowering the community to take action for better mental health. AB - For major physical diseases, it is widely accepted that members of the public will benefit by knowing what actions they can take for prevention, early intervention, and treatment. However, this type of public knowledge about mental disorders (mental health literacy) has received much less attention. There is evidence from surveys in several countries for deficiencies in (a) the public's knowledge of how to prevent mental disorders, (b) recognition of when a disorder is developing, (c) knowledge of help-seeking options and treatments available, (d) knowledge of effective self-help strategies for milder problems, and (e) first aid skills to support others affected by mental health problems. Nevertheless, there is evidence that a range of interventions can improve mental health literacy, including whole-of-community campaigns, interventions in educational settings, Mental Health First Aid training, and information websites. There is also evidence for historical improvements in mental health literacy in some countries. Increasing the community's mental health literacy needs to be a focus for national policy and population monitoring so that the whole community is empowered to take action for better mental health. PMID- 22040222 TI - Metagenomic analysis of DNA viruses in a wastewater treatment plant in tropical climate. AB - Viruses have been detected in the different stages of wastewater treatment plants (WWTPs) at concentrations of 10(8) -10(10) ml(-1) of virus-like particles (VLPs), 10-1000 times higher than in natural aquatic environments, suggesting that WWTPs can be considered as an important reservoir and source of viruses. This study revealed novel diversity and function with the DNA viral communities in the influent, activated sludge, anaerobic digester, and effluent of a domestic WWTP using metagenomics. WWTP was a very specific environment, with less than 5% of the > 936 000 metagenomic sequences obtained (~70-119 Mbp per sample) similar to sequences present in other environmental viromes. Many viruses found in the WWTP were novel, resulting in only < 5-20% of the reads being phylogenetically or functionally assigned. DNA metabolism was observed as the most abundant function with DNA methylase detected at levels 4.2-fold higher than other published viromes, while carbohydrate and amino acids metabolisms were 3.7- and 4.2-fold less abundant respectively. These specific aspects of the WWTP community functions are likely due to high biomass concentration, turnover rate and microbial activity in WWTPs, and likely include mechanisms that help viruses increase their infectivity. Among ~500 genotypes estimated in individual WWTP viromes, > 82% were shared. These data suggested that VLPs of most viral types could be present between 1 and 30 days in the process before they were discharged. Viruses in WWTP and the discharged ones can have potential impacts on the functioning of the wastewater treatment system and on the dynamics of microbial community in the surrounding aquatic environments respectively. PMID- 22040224 TI - XyliMelts time-release adhering discs for night-time oral dryness. AB - Dry mouth can be caused by medication, CPAP use, radiation treatment and a variety of connective tissue diseases, with the prevalence increasing with age. In most individuals, daytime dryness is easily managed. However, except for a new product tested in this study, there is no product lasting longer than an hour that can be used at night to reduce the perception of oral dryness while sleeping. The purpose of this study was to assess whether a self-adhering, slowly dissolving disc that time-releases 500 mg of xylitol, cellulose gum (lubricant and humectant) and mild mint flavour (XyliMelts for Dry Mouth, OraHealth Corp.) used during sleep would reduce perceived morning oral dryness and discomfort. Fifteen subjects self-identified as having morning oral dryness were evaluated first without treatment and again with the use of XyliMelts for Dry Mouth. Measures of initial morning discomfort and perceived wetness demonstrated significant improvement. Perceived oral wetness scores increased more than threefold with the use of XyliMelts for Dry Mouth while sleeping. These findings suggest that XyliMelts for Dry Mouth may be an effective strategy for managing oral dryness that occurs at night. PMID- 22040225 TI - The neuroprotective effect of pyrroloquinoline quinone on traumatic brain injury. AB - Pyrroloquinoline quinone (PQQ) is a water-soluble, anionic, quinonoid substance that has been established as an essential nutrient in animals. Owing to the inherent properties of PQQ as an antioxidant and redox modulator in various systems, PQQ is expected to be used in pharmacological applications in the near future. Although many recent studies have investigated its neuroprotective effects, the effect of PQQ on traumatic brain injury (TBI) has not been examined. In this study we employed Morris water maze (MWM) training, the results of which showed that PQQ led to improved behavioral performance in post-TBI animals. Considering that many experiments have suggested that beta-1,4 galactosyltransferase I (beta-1,4-GalT-I) and -V play significant roles in inflammation and the nervous system, in the present study we used Western blot analysis to study the effect of PQQ on the expression of beta-1,4-GalT-I and -V. We found apparent expression upregulation of beta-1,4-GalT-I and -V after PQQ was systemically administered. Lectin-fluorescent staining with RCA-I also revealed that PQQ contributed to expression upregulation of the galactosidase beta-1 (Gal beta-1), 4-galactosyltransferase N-acylsphingosine (4-GlcNAc) group in microglia and neurons of the cortex and hippocampal CA2 region. In summary, our experiment established that PQQ may play an important role in recovery post-TBI. PMID- 22040226 TI - Pulmonary and hepatic nodular lesions precede the diagnosis of Crohn's disease in an 8-year-old girl: a case study and review of the literature. AB - AIM: To describe a novel clinical observation and to provide a review the literature about lung involvement in children with Crohn disease (CD). METHODS: An 8-year-old girl presented with pulmonary and hepatic granulomatous lesions, followed 6 months later by abdominal and general symptoms, resulting in the diagnosis of CD. Differential diagnosis between CD and sarcoidosis and a review of the literature about lung lesions in children with CD are discussed. RESULTS: Crohn disease can be associated with pulmonary lesions, developing before, at the same time or after occurrence of digestive symptoms. CONCLUSIONS: This report highlights not only the importance of looking for lung lesions in CD but also underscores the necessity of considering the diagnosis of CD in incomplete presentation evoking sarcoidosis. PMID- 22040227 TI - Role of polytetrahedral structures in the elongation and rupture of gold nanowires. AB - We report comprehensive high-accuracy molecular dynamics simulations using the ReaxFF force field to explore the structural changes that occur as Au nanowires are elongated, establishing trends as a function of both temperature and nanowire diameter. Our simulations and subsequent quantitative structural analysis reveal that polytetrahedral structures (e.g., icosahedra) form within the "amorphous" neck regions, most prominently for systems with small diameter at high temperature. We demonstrate that the formation of polytetrahedra diminishes the conductance quantization as compared to systems without this structural motif. We demonstrate that use of the ReaxFF force field, fitted to high-accuracy first principles calculations of Au, combines the accuracy of quantum calculations with the speed of semiempirical methods. PMID- 22040228 TI - Serum adiponectin and type 1 diabetes: the real myth. PMID- 22040229 TI - Influence of chewing force on salivary stress markers as indicator of mental stress. AB - The aim of this study was to investigate the influence of chewing force on salivary stress markers (alpha-amylase activity, salivary cortisol level and secretory immunoglobulin A secretion rate) as indicators of mental stress. Participants comprised 20 healthy men. The first set of saliva specimens (S1) was collected at immediately after a 20-min rest to evaluate stress markers. As stress loading, the participants were required to perform arithmetic calculations for 20 min, after which the second set of saliva specimens (S2) was collected. Each participant was then required to chew a piece of tasteless gum for 10 min, after which the third set of saliva specimens (S3) was collected. After a 20-min rest, the fourth set of saliva specimens (S4) was collected. Weak, habitual and strong chewing forces were assigned. Change rates of stress markers between S2 and S3, and S2 and S4 were calculated. A significant difference was observed in the change rate of cortisol levels between S2 and S3. Cortisol level decreased more under strong chewing than under weak chewing. No significant differences were observed in the change rate of amylase activity or s-IgA secretion rate among the three chewing forces. The results suggest that differences in chewing force influence the salivary cortisol level of the three stress markers, and that a strong chewing force induces a greater reduction in mental stress than a weak one. PMID- 22040230 TI - Candidate mucosal and surrogate biomarkers of inflammatory bowel disease in the era of new technology. AB - OBJECTIVE: There is increasing knowledge of the pathophysiology behind inflammatory bowel disease (IBD) although the exact mechanism is far from fully understood. In the era of new technology, over the last years molecular approaches have shed light on the inflammatory mechanisms and their metabolic end products. This opens for a molecular fingerprinting that can be used in the biomarker field of IBD. There is a great need of biomarkers for prediction of clinical outcome and prognostic biomarker for prediction of therapeutic effects in IBD. Although the biomarker concept is old, so far very few really useful biomarkers exist in IBD. MATERIAL AND METHODS: Here, we review the predictive and prognostic biomarkers in IBD in the era of new technologies with emphasis on the potential of molecular fingerprinting. RESULTS: Very few candidate biomarkers have been documented. The most promising candidate predictor is tumor necrosis factor-alpha, but there is a lack of validation. CONCLUSION: So far, there are few biomarkers documented in IBD, but we are at the start of a new scientific field that will be of great value for the handling of the disease. PMID- 22040231 TI - Retrospective study of necrotizing fasciitis and characterization of its associated methicillin-resistant Staphylococcus aureus in Taiwan. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a prevalent pathogen of necrotizing fasciitis (NF) in Taiwan. A four-year NF cases and clinical and genetic differences between hospital acquired (HA)- and community-acquired (CA)-MRSA infection and isolates were investigated. METHODS: A retrospective study of 247 NF cases in 2004-2008 and antimicrobial susceptibilities, staphylococcal chromosomal cassette mec (SCCmec) types, pulsed field gel electrophoresis (PFGE) patterns, virulence factors, and multilocus sequence typing (MLST) of 16 NF-associated MRSA in 2008 were also evaluated. RESULTS: In 247 cases, 42 microbial species were identified. S. aureus was the major prevalent pathogen and MRSA accounted for 19.8% of NF cases. Most patients had many coexisting medical conditions, including diabetes mellitus, followed by hypertension, chronic azotemia and chronic hepatic disease in order of decreasing prevalence. Patients with MRSA infection tended to have more severe clinical outcomes in terms of amputation rate (p < 0.05) and reconstruction rate (p = 0.001) than those with methicillin-sensitive S. aureus or non-S. aureus infection. NF patients infected by HA-MRSA had a significantly higher amputation rate, comorbidity, C-reactive protein level, and involvement of lower extremity than those infected by CA-MRSA. In addition to over 90% of MRSA resistant to erythromycin and clindamycin, HA-MRSA was more resistant than CA-MRSA to trimethoprim-sulfamethoxazole (45.8% vs. 4%). ST59/pulsotype C/SCCmec IV and ST239/pulsotype A/SCCmec III isolates were the most prevalent CA- and HA-MRSA, respectively in 16 isolates obtained in 2008. In contrast to the gene for gamma hemolysin found in all MRSA, the gene for Panton-Valentine leukocidin was only identified in ST59 MRSA isolates. Other three virulence factors TSST-1, ETA, and ETB were occasionally identified in MRSA isolates tested. CONCLUSION: NF patients with MRSA infection, especially HA-MRSA infection, had more severe clinical outcomes than those infected by other microbial. The prevalent NF-associated MRSA clones in Taiwan differed distinctly from the most predominant NF-associated USA300 CA-MRSA clone in the USA. Initial empiric antimicrobials with a broad coverage for MRSA should be considered in the treatment of NF patients in an endemic area. PMID- 22040232 TI - Death and near death from cardiac arrest during the Boston Marathon. AB - The Boston Marathon has been run for 115 years during which there were three sudden cardiac arrests. The most recent was a near death avoided by rapid cardiopulmonary resuscitation (CPR) and defibrillation. Awareness of the dangers of participating in a marathon, the risk factors associated with sudden death during competition, and the life-saving importance of rapid CPR and defibrillation are essential for participants and event organizers. Available records and reports of the three known cases of cardiac arrest during the Boston Marathon were examined. These cases were identified by representatives of the Boston Athletic Association, which has organized each marathon since its inception. Pertinent literature was reviewed and new information was obtained during interviews of witnesses and rescuers. The data were analyzed in search of shared risk factors for cardiac arrest, death, and the optimal requirements for survival. In 115 years, there were two cardiac deaths and one near death from cardiac arrest. A history of coronary artery disease, advanced age, and prolonged race time are risk factors for sudden cardiac arrest. Rapid application of CPR and defibrillation are essential for survival. Prevention or reduction of life threatening cardiac incidents during marathon races might be achieved if participants of advanced age or with a history of coronary artery disease seek medical clearance prior to entering an event. Those with coronary risk factors should have a discussion with their physician. Availability of trained personnel and defibrillators are important considerations in marathon planning. PMID- 22040233 TI - Fluorescent chemosensors based on spiroring-opening of xanthenes and related derivatives. PMID- 22040234 TI - Caprine prion gene polymorphisms are associated with decreased incidence of classical scrapie in goat herds in the United Kingdom. AB - The application of genetic breeding programmes to eradicate transmissible spongiform encephalopathies in goats is an important aim for reasons of animal welfare as well as human food safety and food security. Based on the positive impact of Prnp genetics on sheep scrapie in Europe in the past decade, we have established caprine Prnp gene variation in more than 1100 goats from the United Kingdom and studied the association of Prnp alleles with disease phenotypes in 150 scrapie-positive goats. This investigation confirms the association of the Met142 encoding Prnp allele with increased resistance to preclinical and clinical scrapie. It reveals a novel association of the Ser127 encoding allele with a reduced probability to develop clinical signs of scrapie in goats that are already positive for the accumulation of disease-specific prion protein in brain or periphery. A United Kingdom survey of Prnp genotypes in eight common breeds revealed eleven alleles in over thirty genotypes. The Met142 encoding allele had a high overall mean allele frequency of 22.6%, whereas the Ser127 encoding allele frequency was considerably lower with 6.4%. In contrast, a well known resistance associated allele encoding Lys222 was found to be rare (0.9%) in this survey. The analysis of Prnp genotypes in Mexican Criollas goats revealed nine alleles, including a novel Phe to Leu substitution in codon 201, confirming that high genetic variability of Prnp can be found in scrapie-free populations. Our study implies that it should be feasible to lower scrapie prevalence in goat herds in the United Kingdom by genetic selection. PMID- 22040235 TI - Huh-7 cell line as an alternative cultural model for the production of human like erythropoietin (EPO). AB - BACKGROUND AND AIMS: Erythropoietin (EPO) is a glycoprotein hormone which is required to regulate the production of red blood cells. Deficiency of EPO is known to cause anemia in chronically infected renal patients and they require regular blood transfusion. Availability of recombinant EPO has eliminated the need for blood transfusion and now it is extensively used for the treatment of anemia. Glycosylation of erythropoietin is essential for its secretion, stability, protein conformation and biological activity. However, maintenance of human like glycosylation pattern during manufacturing of EPO is a major challenge in biotechnology. Currently, Chinese hamster ovary (CHO) cell line is used for the commercial production of erythropoietin but this cell line does not maintain glycosylation resembling human system. With the trend to eliminate non-human constituent from biopharmaceutical products, as a preliminary approach, we have investigated the potential of human hepatoma cell line (Huh-7) to produce recombinant EPO. MATERIALS AND METHODS: Initially, the secretory signal and Kozak sequences was added before the EPO mature protein sequence using overlap extension PCR technique. PCR-amplified cDNA fragments of EPO was inserted into mammalian expression vector under the control of the cytomegalovirus (CMV) promoter and transiently expressed in CHO and Huh-7 cell lines. After RT-PCR analysis, ELISA and Western blotting was performed to verify the immunochemical properties of secreted EPO. RESULTS: Addition of secretory signal and Kozak sequence facilitated the extra-cellular secretion and enhanced the expression of EPO protein. Significant expression (P < 0.05) of EPO was observed in the medium from Huh-7 cell line. CONCLUSION: Huh-7 cell line has a great potential to produce glycosylated EPO, suggesting the use of this cell line to produce glycoproteins of the therapeutic importance resembling to the natural human system. PMID- 22040236 TI - The effect of body coverings on the formation of adipocere in an aqueous environment. AB - Adipocere is a postmortem decomposition product that consists of a mixture of fatty acids. The rate of formation of adipocere from pig adipose tissue in an aqueous environment has been monitored. The effect of various clothing and carpet material types on the process was investigated. The fatty acid composition of the adipocere was determined at regular intervals using gas chromatography-mass spectrometry. Examination of the changes to fatty acid concentrations allowed the degree of adipocere formation in the different environments to be estimated. The study demonstrated that the rate at which adipocere forms is particularly accelerated by the presence of coverings produced from natural materials. Elemental analysis by inductively coupled plasma-mass spectrometry revealed, for the most part, little change to the cations present in the adipocere formed. However, an increase in Ca concentration was observed for tissue wrapped in acrylic carpet, which was associated with a CaCO(3) additive used in the carpet manufacture. PMID- 22040237 TI - Lupus anticoagulant testing: analyzing fresh samples after a single centrifugation and after a 6-8 h delay. AB - BACKGROUND: For automation it is important to know the effect of analyzing fresh samples after a single rather than after two centrifugations, and to determine test stability. METHODS: This study compared silica clotting times (SCT) and dilute Russel's viper venom tests (dRVVT) after one and two centrifugations in 50 fresh plasma samples. Then it compared test results within 4 h to those after 6-8 h of blood drawing in 40 samples. Means, minimums, maximums and quartiles of the paired screen were compared, test ratios were confirmed and correlations, linear regressions and Bland-Altman statistics were calculated. RESULTS: The distributions of test results were nearly identical, regardless of the number of centrifugations or timing of the analysis. The first centrifugation explained 97.7% and 94.8% of the variance of tests results after the second centrifugation for the SCT and dRVVT, respectively. The test results after 6-8 h explained 98.3% and 96.3% of the variance of the SCT-ratios and dRVVT-ratios, respectively, tested within 4 h. Inter-day coefficients of correlation of ratio comparisons were similar to those of the controls values. CONCLUSIONS: Testing of fresh samples after a single centrifugation might replace batch testing of frozen samples after double centrifugation, providing timelier reporting of results and resulting in savings of technician time. PMID- 22040238 TI - Strategies of reducing input sample volume for extracting circulating cell-free nuclear DNA and mitochondrial DNA in plasma. AB - BACKGROUND: Circulating cell-free (ccf) DNA in blood has been suggested as a potential biomarker in many conditions regarding early diagnosis and prognosis. However, misdiagnosis can result due to the limited DNA resources in Biobank's plasma samples or insufficient DNA targets from a predominant DNA background in genetic tests. This study explored several strategies for an efficient DNA extraction to increase DNA amount from limited plasma input. METHODS: Ccf plasma DNA was extracted with three different methods, a phenol-chloroform isoamylalcohol (PCI) method, a High Pure PCR Template Preparation Kit method and a method used for single cell PCR in this group. Subsequently, the total DNA was measured by Nanodrop and the genome equivalents (GE) of the GAPDH housekeeping gene and MTATP 8 gene were measured using a multiplex real-time quantitative PCR for the quantitative assessment of nDNA and mtDNA. RESULTS: Instead of 400-800 MUL (routine input in the laboratory), 50 MULof plasma input enabled the extraction of ccf DNA sufficient for quantitative analysis. Using the PCI method and the kit method, both nDNA and mtDNA could be successfully detected in plasma samples, but nDNA extracted using protocol for single cell PCR was not detectable in 25% of plasma samples. In comparison to the other two methods, the PCI method showed lower DNA purity, but higher concentrations and more GE of nDNA and mtDNA. CONCLUSIONS: The PCI method was more efficient than the other two methods in the extraction of ccf DNA in plasma. Limited plasma is available for ccf DNA analysis. PMID- 22040239 TI - Functional polymorphisms of GSTA1 and GSTO2 genes associated with asthma in Italian children. AB - BACKGROUND: Asthma is an airway disorder characterized by bronchial inflammation. An imbalance between the oxidative forces and the antioxidant defense systems has been implicated in the pathogenesis of asthma. Glutathione S-transferases (GSTs) play an important role in cellular protection against inflammation. Several studies have investigated the genetic variability of GSTM1, GSTP1 and GSTT1 enzymes in asthma development with conflicting results. Moreover, in our previous independent case-control study on GSTs and asthma, we have found that GSTA1 and GSTO2 gene polymorphisms are associated with asthma. The aim of the present study is to analyze if some functional polymorphisms of GSTA1, GSTM1, GSTP1, GSTO2 and GSTT1 are associated with asthma in pediatric patients from Chieti (Italy). METHODS: In this study, we performed an association study on 127 asthmatic children and 126 controls. We screened single nucleotide polymorphisms at GSTA1, GSTO2 and GSTP1 loci. The effects of GSTM1 and GSTT1 null genotype were also investigated. RESULTS: The GSTA1*-69T and GSTO2*D142 variants are associated with the significant increased risk of asthma development in our study population, while GSTM1, GSTP1 and GSTT1 genotype distributions were nearly equal between the control group and asthmatics. CONCLUSIONS: Confirming our previous study, these findings suggest that the GSTA1 and the GSTO2 are asthma susceptible genes involved in increasing the risk of asthma development in the Italian population. PMID- 22040240 TI - The plagiarism project. AB - Plagiarism has been a problem plaguing academia for centuries. The Internet has made it easier than ever to copy material from one electronic document and paste it into another. Many cases are unintentional, as writers are unaware of the rules regarding plagiarism. This paper provides an overview of plagiarism and describes a project in which librarians partnered with the assistant dean of a graduate science program to educate students about the perils of plagiarism and encourage ethical writing practices. PMID- 22040241 TI - Co-streaming classes: a follow-up study in improving the user experience to better reach users. AB - Co-streaming classes have enabled library staff to extend open classes to distance education students and other users. Student evaluations showed that the model could be improved. Two areas required attention: audio problems experienced by online participants and staff teaching methods. Staff tested equipment and adjusted software configuration to improve user experience. Staff training increased familiarity with specialized teaching techniques and troubleshooting procedures. Technology testing and staff training were completed, and best practices were developed and applied. Class evaluations indicate improvements in classroom experience. Future plans include expanding co-streaming to more classes and on-going data collection, evaluation, and improvement of classes. PMID- 22040242 TI - Sharing MedlinePlus(r)/MEDLINE(r) for information literacy education (SMILE): a dental public health information project. AB - The SMILE project represented a partnership among the University of Texas Health Science Center at San Antonio Libraries, the Gateway Clinic in Laredo, and the San Antonio Metropolitan Health District. The project focused on improving dental practitioners' access to reliable information resources and integrating the best evidence into public health dental practice. Through its training program, SMILE cultivated a set of "power information users" among the dentists, dental hygienists, and community health workers (promotores) who provided public health preventive care and oral health education. The dental public health practitioners gained information literacy skills and increased their knowledge about reliable sites such as blogs, PubMed(r), and MedlinePlus(r). This project fostered opportunities for expanded partnerships with public health personnel. PMID- 22040243 TI - Supporting evidence-based medicine: a survey of U.S. medical librarians. AB - This study sought to identify medical librarians' roles in supporting evidence based medicine (EBM) practice; determine whether medical librarians' work settings, work experiences, or job titles made a difference in their EBM responsibilities; and find out medical librarians' perceptions of their roles in EBM practice. An online survey was distributed to U.S. medical librarians. The results showed that medical librarians had positive perceptions of their EBM related responsibilities, which were diverse and specific. Their work experience, work settings, and job title categories related to some of their EBM responsibilities, as well as the nature of some of the responsibilities. PMID- 22040244 TI - Pillbox: a solid dosage medication identification tool. AB - Pillbox is a tool that can be used to rapidly identify solid dosage medications. The database, created and maintained by the National Library of Medicine with the support of the Food and Drug Administration, seeks to enhance patient safety through the identification of solid dosage medication. Users enter physical characteristics of a medication, possible matches are provided, and links to additional resources are offered. A comparison with comparable resources was conducted, and future enhancements to Pillbox are discussed. PMID- 22040245 TI - Lesbian, gay, bisexual, and transgender health issues, disparities, and information resources. AB - Lesbian, gay, bisexual, and transgender (LGBT) persons, while widely diverse in many ways, share health disparities related to the stigma and discrimination they experience, including disproportionate rates of psychiatric disorders, substance abuse, and suicide. Lesbians, gay men, bisexuals, and the transgender communities have additional health concerns and disparities unique to each population. This paper highlights the national recognition of these health issues and disparities and presents web-based information resources about them and their mitigation. PMID- 22040246 TI - Enhancing resident morning report with "daily learning packages". AB - The daily "Morning Report" is a fixture in many residency programs. In the past, librarians have attended this meeting and, in various ways, worked to enhance the resident learning experience. At the academic children's hospital discussed in this study, the concept was taken a step further. Together with the chief residents, the librarian provided a complete "learning package" consisting of the case write-up along with relevant, librarian-filtered, evidence-based information. The learning package was then e-mailed to all residents and some of the attending physicians. This program led to a huge increase in the use of library resources and services as well as a renewed recognition of the value of the library and the librarians. PMID- 22040247 TI - Continual evolution: the experience over three semesters of a librarian embedded in an online evidence-based medicine course for physician assistant students. AB - This column examines the experience, over three years, of a librarian embedded in an online Epidemiology and Evidence-based Medicine course, which is a requirement for students pursuing a Master of Science in Physician Assistant Studies at Pace University. Student learning outcomes were determined, a video lecture was created, and student learning was assessed via a five-point Blackboard test during year one. For years two and three, the course instructor asked the librarian to be responsible for two weeks of course instruction and a total of 15 out of 100 possible points for the course. This gave the librarian flexibility to measure additional outcomes and gather more in-depth assessment data. The librarian then used the assessment data to target areas for improvement in the lessons and Blackboard tests. Revisions made by the librarian positively affected student achievement of learning outcomes, as measured by the assessment conducted the subsequent semester. Plans for further changes are also discussed. PMID- 22040254 TI - Sopranos but not tenors live longer. AB - The longer life spans of females compared to males has been attributed to the effects of sex hormones. Since experimental tests of this possibility in humans are unethical, indirect studies have been relied on for evidence. The present study offers such indirect evidence by comparing life spans of female and male opera singers, since sex hormones are known to influence development of voice. Life spans of sopranos were found to be significantly greater than those of lower voice registered contraltos, even after controlling for birth year. Differences among male opera singers were not statistically significant. The data support the hypothesis that females live longer than males because of the beneficial effects of estrogens on longevity-related genes. PMID- 22040255 TI - Cylindroma appearing in a pre-existing nevus sebaceous. PMID- 22040256 TI - DRG coding practice: a nationwide hospital survey in Thailand. AB - BACKGROUND: Diagnosis Related Group (DRG) payment is preferred by healthcare reform in various countries but its implementation in resource-limited countries has not been fully explored. OBJECTIVES: This study was aimed (1) to compare the characteristics of hospitals in Thailand that were audited with those that were not and (2) to develop a simplified scale to measure hospital coding practice. METHODS: A questionnaire survey was conducted of 920 hospitals in the Summary and Coding Audit Database (SCAD hospitals, all of which were audited in 2008 because of suspicious reports of possible DRG miscoding); the questionnaire also included 390 non-SCAD hospitals. The questionnaire asked about general demographics of the hospitals, hospital coding structure and process, and also included a set of 63 opinion-oriented items on the current hospital coding practice. Descriptive statistics and exploratory factor analysis (EFA) were used for data analysis. RESULTS: SCAD and Non-SCAD hospitals were different in many aspects, especially the number of medical statisticians, experience of medical statisticians and physicians, as well as number of certified coders. Factor analysis revealed a simplified 3-factor, 20-item model to assess hospital coding practice and classify hospital intention. CONCLUSION: Hospital providers should not be assumed capable of producing high quality DRG codes, especially in resource-limited settings. PMID- 22040257 TI - Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats. AB - BACKGROUND: Traumatic brain injury (TBI) evokes a systemic immune response including leukocyte migration into the brain and release of pro-inflammatory cytokines; however, the mechanisms underlying TBI pathogenesis and protection are poorly understood. Due to the high incidence of head trauma in the sports field, battlefield and automobile accidents identification of the molecular signals involved in TBI progression is critical for the development of novel therapeutics. METHODS: In this report, we used a rat lateral fluid percussion impact (LFPI) model of TBI to characterize neurodegeneration, apoptosis and alterations in pro-inflammatory mediators at two time points within the secondary injury phase. Brain histopathology was evaluated by fluoro-jade (FJ) staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, polymerase chain reaction (qRT PCR), enzyme linked immunosorbent assay (ELISA) and immunohistochemistry were employed to evaluate the CCL20 gene expression in different tissues. RESULTS: Histological analysis of neurodegeneration by FJ staining showed mild injury in the cerebral cortex, hippocampus and thalamus. TUNEL staining confirmed the presence of apoptotic cells and CD11b+ microglia indicated initiation of an inflammatory reaction leading to secondary damage in these areas. Analysis of spleen mRNA by PCR microarray of an inflammation panel led to the identification of CCL20 as an important pro-inflammatory signal upregulated 24 h after TBI. Although, CCL20 expression was observed in spleen and thymus after 24 h of TBI, it was not expressed in degenerating cortex or hippocampal neurons until 48 h after insult. Splenectomy partially but significantly decreased the CCL20 expression in brain tissues. CONCLUSION: These results demonstrate that the systemic inflammatory reaction to TBI starts earlier than the local brain response and suggest that spleen- and/ or thymus-derived CCL20 might play a role in promoting neuronal injury and central nervous system inflammation in response to mild TBI. PMID- 22040258 TI - Conventional brain MRI in neuromyelitis optica. AB - BACKGROUND AND PURPOSE: Numerous case series have demonstrated that lesions on brain MRI are common in neuromyelitis optica (NMO), but there has not been an attempt to survey and synthesize the literature on neuro-radiology of brain findings in NMO. OBJECTIVES: To review the studies on conventional brain MRI in NMO and to propose to incorporate characteristic brain MRI lesions into the diagnostic criteria of NMO. METHODS: We searched for articles with descriptions of brain MRI findings in NMO in EBSCO, EMBASE, PubMed/Medline, Science Citation Index, and SCOPUS. RESULTS: Brain abnormalities are seen in majority of NMO patients as disease duration increases. A minority of NMO patients meet Barkhof criteria for space dissemination in multiple sclerosis (MS), and these criteria should not be used to exclude NMO diagnosis. Distinctive brain lesions of NMO are cataloged and described. CONCLUSIONS: Brain lesions in NMO are a consistent feature of the disease. International consensus MRI criteria are needed for NMO analogous to the existing criteria for MS. PMID- 22040260 TI - Methanogenic toluene metabolism: community structure and intermediates. AB - Toluene is a model compound used to study the anaerobic biotransformation of aromatic hydrocarbons. Reports indicate that toluene is transformed via fumarate addition to form benzylsuccinate or by unknown mechanisms to form hydroxylated intermediates under methanogenic conditions. We investigated the mechanism(s) of syntrophic toluene metabolism by a newly described methanogenic enrichment from a gas condensate-contaminated aquifer. Pyrosequencing of 16S rDNA revealed that the culture was comprised mainly of Clostridiales. The predominant methanogens affiliated with the Methanomicrobiales. Methane production from toluene ranged from 72% to 79% of that stoichiometrically predicted. Isotope studies using (13)C(7) toluene showed that benzylsuccinate and benzoate transiently accumulated revealing that members of this consortium can catalyse fumarate addition and subsequent reactions. Detection of a BssA gene fragment in this culture further supported fumarate addition as a mechanism of toluene activation. Transient formation of cresols, benzylalcohol, hydroquinone and methylhydroquinone suggested alternative mechanism(s) for toluene metabolism. However, incubations of the consortium with (18)O-H(2)O showed that the hydroxyl group in these metabolites did not originate from water and abiotic control experiments revealed abiotic formation of hydroxylated species due to reactions of toluene with sulfide and oxygen. Our results suggest that toluene is activated by fumarate addition, presumably by the dominant Clostridiales. PMID- 22040259 TI - Incentive device improves spacer technique but not clinical outcome in preschool children with asthma. AB - AIM: To investigate the influence of an incentive device, the Funhaler, on spacer technique and symptom control in young children with asthma and recurrent wheeze. METHODS: Randomised controlled trial where 132 2-6 year old asthmatic children received regular inhaled fluticasone through Aerochamber Plus, or Funhaler. The setting was a research clinic at Princess Margaret Hospital for Children, Perth, Australia. Subjects were followed up for a year. The main outcome measure was asthma symptoms. Proficiency in spacer technique was measured as salbutamol inhaled from spacer onto filter. Quality of life was measured every three months. Groups were compared in terms of spacer technique, symptoms and quality of life. The relationship between spacer technique and clinical outcome was examined. RESULTS: There was no difference between Funhaler and Aerochamber groups in wheeze free days, cough free days, bronchodilator free days or quality of life (P = 0.90, 0.87, 0.74 and 0.11 respectively). Spacer technique was better in the Funhaler group (P = 0.05), particularly in subjects younger than 4 years of age (P = 0.002). Drug dose on filter (as the mean of five 100 mg doses) ranged from zero to 136 mg. CONCLUSIONS: Use of Funhaler incentive device does not improve clinical outcome, but improves spacer technique in children younger than 4 years. Variability in drug delivery is large in young children using pressurised metered dose inhalers and spacers. PMID- 22040261 TI - National cultures, performance appraisal practices, and organizational absenteeism and turnover: a study across 21 countries. AB - Performance appraisal (PA) is a key human resource activity in organizations. However, in this global economy, we know little about how societal cultures affect PA practices. In this study, we address this gap by focusing on 2 complementary issues: (a) the influence of societal (national) cultural practices on PA practices adopted by organizations and (b) the contribution of the level of congruence between societal cultural practices and the characteristics of organizational PA practices to absenteeism and turnover. The results, based on a large data set across multiple countries and over 2 time periods, support the hypothesized effects of societal (national) cultural practices on particular PA practices and the interactive effects of societal cultural practices and PA practices on absenteeism and turnover. We discuss theoretical and practical implications of our findings. PMID- 22040262 TI - Within-person relationships between mood and creativity. AB - State mood has been proposed as a facilitator of creative behavior. Whereas positive mood compared to neutral mood generally facilitates creative performance, mood effects are weaker and less consistent when positive mood is compared to negative mood. These inconsistent results may be due to focusing only on mood valence, while neglecting or confounding mood activation. The current study is based on the dual-pathway model, which describes separate roles for mood valence and mood activation in facilitating creativity. We used experience sampling methodology to investigate the concurrent and lagged effects of mood valence and activation on creative process engagement (CPE) within-person over time among individuals working on a long-term project requiring creativity. We also investigated the moderating effects of individual differences in goal orientation and supervisory support on within-person mood-creativity relationships. As expected, we found that activating positive and activating negative moods were positively associated with concurrent CPE, whereas deactivating moods of both valences were negatively related to CPE. Activating negative mood had a significant lagged effect on CPE, whereas activating positive mood did not. We also found that activating positive mood was more strongly related to concurrent CPE among individuals with high rather than low learning goal orientation. Further, activating positive mood interacted with prove goal orientation and supervisory support for creativity, such that activating positive mood had the strongest association with CPE when both prove goal orientation and supervisory support were high. PMID- 22040263 TI - Personnel selection as a signaling game. AB - Personnel selection involves exchanges of information between job market actors (applicants and organizations). These actors do not have an incentive to exchange accurate information about their ability and commitment to the employment relationship unless it is to their advantage. This state of affairs explains numerous phenomena in personnel selection (e.g., faking). Signaling theory describes a mechanism by which parties with partly conflicting interests (and thus an incentive for deception) can nevertheless exchange accurate information. We apply signaling theory to personnel selection, distinguishing between adaptive relationships between applicants and organizations, among applicants, and among organizations. In each case, repeated adaptations and counteradaptations between actors can lead to situations of equilibrium or escalation (arms races). We show that viewing personnel selection as a network of adaptive relationships among job market actors enables an understanding of both classic and underexplored micro- and macro-level selection phenomena and their dynamic interactions. PMID- 22040264 TI - An observational study to quantify manual adjustments of the inspired oxygen fraction in extremely low birth weight infants. AB - AIM: To quantify manual fraction of inspired oxygen (FiO(2)) adjustments performed by caregivers in extremely low birth weight (ELBW; <=1000 g) infants, in relation to oxygen saturation (SpO(2)) and bedside care. METHODS: In a single centre study, FiO(2) , SpO(2) and alarm limits of ELBW infants were collected for 3 days continuously, while caregivers were filmed. A descriptive analysis, focused on manual FiO(2) adjustments, was performed. RESULTS: Twelve ELWB infants were included. Total recording time was 726 h. FiO(2) was increased 851 times and decreased 1309 times; median (range) step size was 5% (1% to 65%) and -3% (-1% to -65%), respectively. Wide variation of FiO(2) adjustments for equal levels of SpO(2) was observed in all included infants. One hundred and twenty-six of 136 FiO(2) adjustments with a step size >=15% and 111 of 171 desaturations <70% were associated with medical or nursing procedures. When FiO(2) was >21%, alarm limits for SpO(2) were set according to protocol (88-94%) in 64% of the time. Within these periods, SpO(2) was >94% for 30% and <88% for 16% of the time. CONCLUSIONS: Manual FiO(2) adjustments varied widely in frequency and step size. Deep desaturations and large FiO(2) adjustments were associated with medical or nursing procedures. When large adjustments are really necessary, it will be challenging to implement them in an automatic adjustment device. PMID- 22040265 TI - Organometallic complexes of graphene: toward atomic spintronics using a graphene web. AB - Graphene|metal|ligand systems open a new realm in surface magnetochemistry. We show that by trapping metal atoms in the two-dimensional potential lattice of a graphene-ligand interface it is possible to build a chemical analogue of an optical lattice, a key setup in quantum information and strongly correlated systems. Employing sophisticated first-principles calculations, we studied electronic and dynamic properties of graphene|metal|ligand assemblies and showed that there is a general principle--spin-charge separation in pi-d systems--that underlies the possibility of synthesizing and controlling such systems. We find that ligands can work as a local gate to control the properties of trapped metal atoms and can impose bosonic or fermionic character on such atomic nets, depending on the ligand's nature. Remarkably, the magnetization energy in such systems reaches record-high values of ca. 400 meV, which makes the respective magnetic phenomena utilizable at room temperature. Accompanied by spin polarization of the graphene pi-conjugated system it leads to spin-valve materials and brings the realization of quantum computing one step closer. PMID- 22040266 TI - Atrionatriuretic peptide improves left ventricular function after myocardial global ischemia-reperfusion in hypoxic hearts. AB - Atrionatriuretic peptide (ANP) is reported to be useful for attenuating myocardial ischemia-reperfusion injury and improving left ventricular function after reperfusion. However, ANP may be either ineffectual or harmful in cases where the myocardium has been chronically hypoxic since birth. This can be a result of the concomitant high levels of cyclic guanosine monophosphate (cGMP) produced within the myocardium. This study aimed to verify the validity of using ANP to improve left ventricular function after myocardial ischemia-reperfusion injury. For this purpose, a cyanotic congenital disease model that was developed using isolated rat hearts was used. Hearts were obtained from Sprague-Dawley rats that were housed from birth until 6 weeks of age either in a hypoxic environment with 13-14% FiO(2) (hypoxic group) or in ambient air (normoxic group). These hearts were subjected to 30min of normothermic global ischemia followed by 30min of reperfusion using the Langendorff technique. Left ventricular functional recovery in hearts administered ANP (0.1uM) into the reperfusion solution was compared with those hearts that were not administered ANP in both hypoxic (without ANP: n=6, with ANP: n=6, with ANP and HS-142-1[an antagonist of ANP]: n=6) and normoxic hearts (without ANP: n =6, with ANP: n=6). In the hypoxic hearts, ANP administration improved the percent recovery of the left ventricular developed pressure (76.3+/-9.2% without ANP vs. 86.9+/-6.7% with ANP), maximum first derivative of the left ventricular pressure (82.4+/-1.1% without ANP vs. 95.8+/-6.5% with ANP), and heart rate (85.6+/-4.7% without ANP vs. 96.1+/-5.2% with ANP) after reperfusion. The improvement and recovery of these cardiac functions were closely related to significantly increased levels of postischemic cGMP release after ANP administration. The effect of ANP was blocked by HS-142-1. The improvements observed in the hypoxic group were similar to those found in the normoxic group. ANP administration during reperfusion improved left ventricular function after myocardial acute global ischemia-reperfusion equally in both the chronically hypoxic and age-matched normoxic groups. PMID- 22040267 TI - Near infrared transcranial laser therapy applied at various modes to mice following traumatic brain injury significantly reduces long-term neurological deficits. AB - Near-infrared transcranial laser therapy (TLT) has been found to modulate various biological processes including traumatic brain injury (TBI). Following TBI in mice, in this study we assessed the possibility of various near-infrared TLT modes (pulsed versus continuous) in producing a beneficial effect on the long term neurobehavioral outcome and brain lesions of these mice. TBI was induced by a weight-drop device, and neurobehavioral function was assessed from 1 h to 56 days post-trauma using the Neurological Severity Score (NSS). The extent of recovery is expressed as the difference in NSS (dNSS), the difference between the initial score and that at any other later time point. An 808-nm Ga-Al-As diode laser was employed transcranially 4, 6, or 8 h post-trauma to illuminate the entire cortex of the brain. Mice were divided into several groups of 6-8 mice: one control group that received a sham treatment and experimental groups that received either TLT continuous wave (CW) or pulsed wave (PW) mode transcranially. MRI was taken prior to sacrifice at 56 days post-injury. From 5-28 days post-TBI, the NSS of the laser-treated mice were significantly lower (p<0.05) than those of the non-laser-treated control mice. The percentage of surviving mice that demonstrated full recovery at 56 days post-CHI (NSS=0, as in intact mice) was the highest (63%) in the group that had received TLT in the PW mode at 100 Hz. In addition, magnetic resonance imaging (MRI) analysis demonstrated significantly smaller infarct lesion volumes in laser-treated mice compared to controls. Our data suggest that non-invasive TLT of mice post-TBI provides a significant long term functional neurological benefit, and that the pulsed laser mode at 100 Hz is the preferred mode for such treatment. PMID- 22040269 TI - Protective effects of phlorotannins against ultraviolet B radiation in zebrafish (Danio rerio). AB - Exposure to ultraviolet B (UV-B) radiation has been associated with a variety of adverse effects in all forms of life, including micro-organisms, plants, animals and humans. Ultraviolet B induces cell damage at the molecular level and consequently organisms must employ strategies to protect themselves from sunlight and to repair UV-B-induced cellular damage. In this study, the UV-B protective effects of four different phlorotannins isolated from a brown alga (Ecklonia cava) were determined using zebrafish (Danio rerio) as an in vivo model. Zebrafish embryos were pretreated with phlorotannins and exposed to UV-B (50 mJ/cm(2)). The heart rate, generation of reactive oxygen species and nitric oxide, cell death and hyperpigmentation were assessed in order to evaluate UV-B induced photo-damage. Treatment of the embryos with the algal phorotannins reduced UV-B-induced reactive oxygen species and nitric oxide levels, protected against UV-B-induced cell death and significantly reduced hyperpigmentation. We therefore suggest that phlorotannins isolated from E. cava can protect against UV B radiation. Editor Note. Readers of the journal may be unfamiliar with the use of zebrafish embryos in research studies. There is no indication in this article of an ethical review of the study. This is because the use of fish embryos in research, at least in the UK, is not subject to a licensing procedure if they are less than 5 days post fertilization (dpf). In this study the embryos were 2 dpf. PMID- 22040268 TI - Community-associated methicillin-resistant Staphylococcus aureus bacteremia and endocarditis among HIV patients: a cohort study. AB - BACKGROUND: HIV patients are at increased risk of development of infections and infection-associated poor health outcomes. We aimed to 1) assess the prevalence of USA300 community-associated methicillin-resistant Staphylococcus aureus (CA MRSA) among HIV-infected patients with S. aureus bloodstream infections and. 2) determine risk factors for infective endocarditis and in-hospital mortality among patients in this population. METHODS: All adult HIV-infected patients with documented S. aureus bacteremia admitted to the University of Maryland Medical Center between January 1, 2003 and December 31, 2005 were included. CA-MRSA was defined as a USA 300 MRSA isolate with the MBQBLO spa-type motif and positive for both the arginine catabolic mobile element and Panton-Valentin Leukocidin. Risk factors for S. aureus-associated infective endocarditis and mortality were determined using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Potential risk factors included demographic variables, comorbid illnesses, and intravenous drug use. RESULTS: Among 131 episodes of S. aureus bacteremia, 85 (66%) were MRSA of which 47 (54%) were CA-MRSA. Sixty-three patients (48%) developed endocarditis and 10 patients (8%) died in the hospital on the index admission Patients with CA-MRSA were significantly more likely to develop endocarditis (OR = 2.73, 95% CI = 1.30, 5.71). No other variables including comorbid conditions, current receipt of antiretroviral therapy, pre culture severity of illness, or CD4 count were significantly associated with endocarditis and none were associated with in-hospital mortality. CONCLUSIONS: CA MRSA was significantly associated with an increased incidence of endocarditis in this cohort of HIV patients with MRSA bacteremia. In populations such as these, in which the prevalence of intravenous drug use and probability of endocarditis are both high, efforts must be made for early detection, which may improve treatment outcomes. PMID- 22040270 TI - Right ventricular dysfunction is a predictor of non-response and clinical outcome following cardiac resynchronization therapy. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) is an established treatment in advanced heart failure (HF). However, an important subset does not derive a significant benefit. Despite an established predictive role in HF, the significance of right ventricular (RV) dysfunction in predicting clinical benefit from CRT remains unclear. We investigated the role of RV function, assessed by cardiovascular magnetic resonance (CMR), in predicting response to and major adverse clinical events in HF patients undergoing CRT. METHODS: Sixty consecutive patients were evaluated with CMR prior to CRT implantation in a tertiary cardiac centre. The primary end-point was a composite of death from any cause or unplanned hospitalization for a major cardiovascular event. The secondary end point was response to therapy, defined as improvement in left ventricular ejection fraction >= 5% on echocardiography at one year. RESULTS: Eighteen patients (30%) met the primary end-point over a median follow-up period of 26 months, and 27 out of 56 patients (48%) were considered responders to CRT. On time-to-event analysis, only atrial fibrillation (HR 2.6, 95% CI 1.02-6.84, p = 0.047) and RV dysfunction, either by a reduced right ventricular ejection fraction-RVEF (HR 0.96, 95% CI 0.94-0.99, p = 0.006) or tricuspid annular plane systolic excursion-TAPSE (HR 0.88, 95% CI, 0.80-0.96, p = 0.006), were significant predictors of adverse events. On logistic regression analysis, preserved RVEF (OR 1.05, 95% CI 1.01-1.09, p = 0.01) and myocardial scar burden (OR 0.90, 95% CI 0.83-0.96, p = 0.004) were the sole independent predictors of response to CRT. Patients with marked RV dysfunction (RVEF < 30%) had a particularly low response rate (18.2%) to CRT. CONCLUSIONS: Right ventricular function is an important predictor of both response to CRT and long-term clinical outcome. Routine assessment of the right ventricle should be considered in the evaluation of patients for CRT. PMID- 22040271 TI - What helps children to be more active and less sedentary? Perceptions of mothers living in disadvantaged neighbourhoods. AB - BACKGROUND: Increasing children's participation in physical activity and decreasing time spent in sedentary behaviours is of great importance to public health. Despite living in disadvantaged neighbourhoods, some children manage to engage in health-promoting physical activity and avoid high levels of screen based activities (i.e. watching TV, computer use and playing electronic games). Understanding how these children manage to do well and whether there are unique features of their home or neighbourhood that explain their success is important for informing strategies targeting less active and more sedentary children. The aim of this qualitative study was to gain in-depth insights from mothers regarding their child's resilience to low physical activity and high screen-time. METHODS: Semi-structured face-to-face interviews were conducted with 38 mothers of children who lived in disadvantaged neighbourhoods in urban and rural areas of Victoria, Australia. The interviews were designed to gain in-depth insights about perceived individual, social and physical environmental factors influencing resilience to low physical activity and high screen-time. RESULTS: Themes relating to physical activity that emerged from the interviews included: parental encouragement, support and modelling; sports culture in a rural town; the physical home and neighbourhood environment; child's individual personality; and dog ownership. Themes relating to screen-time behaviours encompassed: parental control; and child's individual preferences. CONCLUSIONS: The results offer important insights into potential avenues for developing 'resilience' and increasing physical activity and reducing screen-time among children living in disadvantaged neighbourhoods. In light of the negative effects of low physical activity and high levels of screen-time on children's health, this evidence is urgently needed. PMID- 22040272 TI - Family resources study: part 1: family resources, family function and caregiver strain in childhood cancer. AB - BACKGROUND: Severe illness can disrupt family life, cause family dysfunction, strain resources, and cause caregiver burden. The family's ability to cope with crises depends on their resources. This study sought to assess families of children with cancer in terms of family function-dysfunction, family caregiver strain and the adequacy of family resources using a new family resources assessment instrument. METHODS: This is a cross-sectional study involving 90 Filipino family caregivers of children undergoing cancer treatment. This used a self-administered questionnaire composed of a new 12-item family resources questionnaire (SCREEM-RES) based on the SCREEM method of analysis, Family APGAR to assess family function-dysfunction; and Modified Caregiver Strain Index to assess strain in caring for the patient. RESULTS: More than half of families were either moderately or severely dysfunctional. Close to half of caregivers were either predisposed to strain or experienced severe strain, majority disclosed that their families have inadequate economic resources; many also report inaccessibility to medical help in the community and insufficient educational resources to understand and care for their patients. Resources most often reported as adequate were: family's faith and religion; help from within the family and from health providers. SCREEM-RES showed to be reliable with Cronbach's alpha of 0.80. There is good inter-item correlation between items in each domain: 0.24-0.70. Internal consistency reliability for each domain was also good: 0.40-0.92. Using 2-point scoring system, Cronbach's alpha were slightly lower: full scale (0.70) and for each domain 0.26-.82. Results showed evidence of association between family resources and family function based on the family APGAR but none between family resources and caregiver strain and between family function and caregiver strain. CONCLUSION: Many Filipino families of children with cancer have inadequate resources, especially economic; and are moderately or severely dysfunctional. Many caregivers are predisposed to caregiver strain or are already experiencing severe strain. To provide appropriate care for these families, physicians should regularly assess family function, resources and strain experienced by caregivers. The SCREEM-RES questionnaire used in this study is a helpful and reliable instrument to assess adequacy of family resources. PMID- 22040273 TI - Rapid in situ repeatable analysis of drugs in powder form using reflectance near infrared spectroscopy and multivariate calibration. AB - This study takes the first step toward in situ analysis of powder drugs which does not require any alteration of the samples. A fast, inexpensive analytical method based on reflectance near-infrared (NIR) spectrometry and multivariate calibration was applied. A diode-array fiber-optic portable spectrometer in the 900-1700 nm range was employed. Samples were laboratory-prepared ternary powders (diacetylmorphine, caffeine, and paracetamol). Partial least squares regression was applied. The choice of the standard samples for calibration and validation was performed through a D-optimal experimental design. The explained variance was higher than 90%, and the relative root mean square errors were <2%. The number of principal components (6) was very low when compared with the number of raw variables (356 absorbance values). Response plots showed slopes and intercepts were very close to optimal values. Correlation coefficients ranged between 0.909 and 0.989. The method here proposed proved to be competitive with Fourier transform NIR spectrometry. PMID- 22040275 TI - Transcriptomic responses to aluminum stress in soybean roots. AB - Aluminum (Al) toxicity is the primary limitation to crop production and plant growth in acid soils. Soybean has multiple mechanisms of Al resistance including the complexing and exclusion of Al in root apices by Al-induced citrate secretion. Microarray analysis is available for the identification of genes in soybean. In the present study, Affymetrix soybean genome array was used to identify the Al-induced differentially expressed genes in Al-resistant genotype Jiyu 70. With a cutoff of > 2.0-fold (p < 0.05) between non Al-treated and Al treated root apices, 561 genes were upregulated and 78 genes were downregulated when roots were exposed to 30 MUmol/L AlCl(3) for 4 h. Quantitative real-time PCR was used to test the microarray data. The analysis showed that nearly half of the Al-responsive genes were of unknown biological function. A higher proportion of genes related to transcription regulation and cell wall processes were observed in Al-induced up- and downregulated genes, respectively. Some genes homologous to the citrate transporter MATE family gene or C(2)H(2) family transcription factor gene, STOP1, were detected in our analysis. Some genes related to lignin deposition were upregulated, which might be related to Al-induced root elongation inhibition. PMID- 22040276 TI - Predicting the wetting dynamics of a two-liquid system. AB - We propose a new theoretical model of dynamic wetting for systems comprising two immiscible liquids, in which one liquid displaces another from the surface of a solid. Such systems are important in many industrial processes and the natural world. The new model is an extension of the molecular-kinetic theory of wetting and offers a way to predict the dynamics of a two-liquid system from the individual wetting dynamics of its parent liquids. We also present the results of large-scale molecular dynamics simulations for one- and two-liquid systems and show them to be in good agreement with the new model. Finally, we show that the new model is consistent with the limited data currently available from experiment. PMID- 22040277 TI - Easier detection of invertebrate "identification-key characters" with light of different wavelengths. AB - The marine alpha-taxonomist often encounters two problems. Firstly, the "environmental dirt" that is frequently present on the specimens and secondly the difficulty in distinguishing key-features due to the uniform colours which fixed animals often adopt.Here we show that illuminating animals with deep-blue or ultraviolet light instead of the normal white-light abrogates both difficulties; dirt disappears and important details become clearly visible. This light regime has also two other advantages. It allows easy detection of very small, normally invisible, animals (0.1 MUm range). And as these light wavelengths can induce fluorescence, new identification markers may be discovered by this approach. PMID- 22040278 TI - Zn(II)-bis(cyclen) complexes and the imaging of apoptosis/necrosis. AB - In vivo cell-death imaging is still a challenging issue. Until now, only (99m)Tc labeled HYNIC-rh-annexin A5 has been extensively studied in clinical trials. In the ongoing search for an alternative imaging agent, we synthesized a series of fluorescent zinc-cyclen complexes as annexin A5 mimics and studied structural variations on the uptake behavior of cells undergoing apoptosis/necrosis. The number of cyclen chelators was varied and the spacer separating cyclen from the central scaffold was modified. Five zinc-cyclen complexes were labeled with fluorescein for flow cytometric studies and one was labeled with (18)F for in vivo applications. Jurkat cells were treated with staurosporine to induce apoptosis/necrosis, incubated with the fluorescein-labeled zinc complexes and analyzed them by flow cytometry. Fluorescent annexin A5 and propidium iodide were applied as reference dyes. Flow cytometry revealed greater accumulation of zinc cyclen complexes in staurosporine treated cells. The uptake was contingent on the presence of zinc and the fluorescence intensity was dependent on the number of zinc-cyclen groups. Confocal laser scanning microscopy showed the {bis[Zn(cyclen)]}(4+) complex distributed throughout the cytosol different to annexin A5. Owing to the structural similarity of the bis-cyclen ligands with CXCR4 binding bis-cyclam derivatives the zinc-cyclen complex uptake was challenged with the meta derivative of AMD3100. Lack of uptake depletion in staurosporine treated cells ruled out measurable CXCR4 interaction. PET imaging using the (18)F labeled zinc-cyclen complex revealed significantly higher uptake in an irradiated Dunning R3327-AT1 prostate tumor as compared to the contralateral control tumor. PET imaging of a HelaMatu tumor model additionally showed an increased uptake after taxol treatment. It could be demonstrated that the fluorescent zinc-cyclen complexes offer potential as new agents for flow cytometry and microscopic imaging of cell death. In addition, the (18)F labeled analogue holds promise for in vivo applications providing informations about cell death after radiation therapy and cytostatic drug treatment. PMID- 22040279 TI - Erosive pustular dermatosis of the scalp from topical minoxidil 5% solution. PMID- 22040280 TI - A comparison of active ingredients and preservatives between brand name and generic topical glaucoma medications using liquid chromatography-tandem mass spectrometry. AB - BACKGROUND: This work compares the concentration of active ingredients and preservatives in commonly used brand name versus generic glaucoma medications. MATERIALS AND METHODS: Active ingredient and benzalkonium chloride (BAK) concentrations in brand name latanoprost and dorzolamide-timolol were each compared to two generic counterparts using liquid chromatography-mass spectrometry at baseline and after exposure to 25 degrees C and 50 degrees C for 30 days. Micro flow imaging was used to quantify particulate material greater than one micron in diameter. RESULTS: Brand name formulations contained active ingredients and BAK in concentrations that were generally in agreement with their package inserts at baseline. The two generic formulations of latanoprost contained baseline levels of active ingredients that were 10% greater than their labeled value. Generic latanoprost formulations had significant loss of active ingredient concentration after exposure to 25 degrees C and 50 degrees C for 30 days. Both generic and brand name dorzolamide-timolol appeared relatively resistant to degradation. BAK concentrations remained stable at 25 degrees C but decreased in some bottles at 50 degrees C. Bottles of both generic medications had higher levels of particulate matter compared to brand name versions. CONCLUSIONS: Exposure to temperatures at the high end of the labeled value may lead to a significant decrease in concentration of active ingredients in generic formulations that could influence clinical efficacy. Re-evaluation of intraocular pressure lowering efficacy may be indicated in glaucoma patients switching from brand name to generic formulations. PMID- 22040281 TI - Determining level of care appropriateness in the patient journey from acute care to rehabilitation. AB - BACKGROUND: The selection of patients for rehabilitation, and the timing of transfer from acute care, are important clinical decisions that impact on care quality and patient flow. This paper reports utilization review data on inpatients in acute care with stroke, hip fracture or elective joint replacement, and other inpatients referred for rehabilitation. It examines reasons why acute level of care criteria are not met and explores differences in decision making between acute care and rehabilitation teams around patient appropriateness and readiness for transfer. METHODS: Cohort study of patients in a large acute referral hospital in Australia followed with the InterQual utilization review tool, modified to also include reasons why utilization criteria are not met. Additional data on team decision making about appropriateness for rehabilitation, and readiness for transfer, were collected on a subset of patients. RESULTS: There were 696 episodes of care (7189 bed days). Days meeting acute level of care criteria were 56% (stroke, hip fracture and joint replacement patients) and 33% (other patients, from the time of referral). Most inappropriate days in acute care were due to delays in processes/scheduling (45%) or being more appropriate for rehabilitation or lower level of care (30%).On the subset of patients, the acute care team and the utilization review tool deemed patients ready for rehabilitation transfer earlier than the rehabilitation team (means of 1.4, 1.3 and 4.0 days from the date of referral, respectively). From when deemed medically stable for transfer by the acute care team, 28% of patients became unstable. From when deemed stable by the rehabilitation team or utilization review, 9% and 11%, respectively, became unstable. CONCLUSIONS: A high proportion of patient days did not meet acute level of care criteria, due predominantly to inefficiencies in care processes, or to patients being more appropriate for an alternative level of care, including rehabilitation. The rehabilitation team was the most accurate in determining ongoing medical stability, but at the cost of a longer acute stay.To avoid inpatients remaining in acute care in a state of 'terra nullius', clinical models which provide rehabilitation within acute care, and more efficient movement to a rehabilitation setting, is required. Utilization review could have a decision support role in the determination of medical stability. PMID- 22040282 TI - Are there ethnic differences in impulsive/compulsive behaviors in Parkinson's disease? AB - BACKGROUND AND PURPOSE: Recent studies have suggested increased prevalence of impulsive/compulsive behaviors (ICB) in patients with Parkinson's disease (PD) as compared to general population in different ethnic groups. The spectrum of these behaviors includes dopamine dysregulation syndrome (DDS), punding, pathological gambling (PG), hypersexuality (HS), binge eating (BE), and compulsive shopping (CS). METHODS: Two hundred and seventy-eight consecutive patients with idiopathic PD regularly followed-up at an outpatient clinic were interviewed and screened for the ICB between September 2008 and December 2008 using designated diagnostic criteria. All patients who screened positive for ICB or obsessive-compulsive disorder (OCD) were further confirmed by an experienced psychiatrist. RESULTS: Of all the studied patients, 15 patients confirmed to have ICB (lifetime prevalence: 5.60%), 3 (1.12%) were diagnosed to have DDS, 1 (0.37%) punding, 4 (1.49%) PG, 8 (2.99%) HS, 1 (0.37%) BE, 0 (0%) CS. OCD was found in one patient (0.37%). CONCLUSIONS: The prevalence of ICB is lower in Taiwan as compared with the Caucasians, with similar risk factors. The possible reasons include differences in ethnicity, environmental, cultural, and social factors as well as the dosage and selection of dopaminergic medications. PMID- 22040283 TI - Unveiling microbial life in the new deep-sea hypersaline Lake Thetis. Part II: a metagenomic study. AB - So far only little is known about the microbial ecology of Mediterranean deep-sea hypersaline anoxic lakes (DHALs). These brine lakes were formed by evaporite dissolution/brine seeps and are important model environments to provide insights into possible metabolisms and distributions of microorganisms on the early Earth. Our study on the Lake Thetis, a new thalassohaline DHAL located South-East of the Medriff Corridor, has revealed microbial communities of contrasting compositions with a high number of novel prokaryotic candidate divisions. The major finding of our present work is co-occurrence of at least three autotrophic carbon dioxide fixation pathways in the brine-seawater interface that are likely fuelled by an active ramified sulphur cycle. Genes for the reductive acetyl-CoA and reductive TCA pathways were also found in the brine suggesting that these pathways are operational even at extremely elevated salinities and that autotrophy is more important in hypersaline environments than previously assumed. Surprisingly, genes coding for RuBisCo were found in the highly reduced brine. Three types of sulphide oxidation pathways were found in the interface. The first involves a multienzyme Sox complex catalysing the complete oxidation of reduced sulphur compounds to sulphate, the second type recruits SQR sulphide:quinone reductase for oxidation of sulphide to elemental sulphur, which, in the presence of sulphide, could further be reduced by polysulphide reductases in the third pathway. The presence of the latter two allows a maximal energy yield from the oxidation of sulphide and at the same time prevents the acidification and the accumulation of S(0) deposits. Amino acid composition analysis of deduced proteins revealed a significant overrepresentation of acidic residues in the brine compared with the interface. This trait is typical for halophilic organisms as an adaptation to the brine's extreme hypersalinity. This work presents the first metagenomic survey of the microbial communities of the recently discovered Lake Thetis whose brine constitutes one of saltiest water bodies ever reported. PMID- 22040284 TI - Effect on the production of soluble endoglin from human choriocarcinoma cells by preeclampsia sera. AB - PROBLEM: The soluble endoglin (sEng) is an antiangiogenic protein that may inhibit TGF-beta1 signaling and endothelial nitric oxide synthase activation in endothelial cells. The levels of sEng increased in sera obtained from preeclampsia. The factors that increase the sEng in preeclampsia have not been known well. To investigate the factors that may increase sEng in preeclampsia, we examined the effect of preeclampsia sera on the production of sEng from human choriocarcinoma (JEG-3) cells. METHODS: Serum samples were taken from women with normal pregnancy and from those with preeclampsia. JEG-3 cells were cultured with serum for 24 hrs, and the sEng levels in supernatants and expression of sEng and Hemo oxygenase-1 (HO-1) mRNA in cells were measured. RESULTS: The addition of preeclampsia sera into JEG-3 cells led to increased release of sEng and expression of Eng mRNA. Preeclampsia sera inhibited the expression of HO-1 mRNA in JEG-3 cells. CONCLUSION: The results suggest that preeclampsia sera may increase the protein production of sEng and mRNA expression of Eng from JEG-3 cells like trophoblast without hypoxia and that in addition to hypoxia, preeclampsia sera may play a role of high level of serum sEng in preeclampsia patients. Decreased HO-1 activity may relate to increased sEng release. PMID- 22040285 TI - Slow and steady wins the race: a randomized clinical trial of acceptance and commitment therapy targeting shame in substance use disorders. AB - OBJECTIVE: Shame has long been seen as relevant to substance use disorders, but interventions have not been tested in randomized trials. This study examined a group-based intervention for shame based on the principles of acceptance and commitment therapy (ACT) in patients (N = 133; 61% female; M = 34 years old; 86% Caucasian) in a 28-day residential addictions treatment program. METHOD: Consecutive cohort pairs were assigned in a pairwise random fashion to receive treatment as usual (TAU) or the ACT intervention in place of 6 hr of treatment that would have occurred at that same time. The ACT intervention consisted of three 2-hr group sessions scheduled during a single week. RESULTS: Intent-to treat analyses demonstrated that the ACT intervention resulted in smaller immediate gains in shame, but larger reductions at 4-month follow-up. Those attending the ACT group also evidenced fewer days of substance use and higher treatment attendance at follow-up. Effects of the ACT intervention on treatment utilization at follow-up were statistically mediated by posttreatment levels of shame, in that those evidencing higher levels of shame at posttreatment were more likely to be attending treatment at follow-up. Intervention effects on substance use at follow-up were mediated by treatment utilization at follow-up, suggesting that the intervention may have had its effects, at least in part, through improving treatment attendance. CONCLUSIONS: These results demonstrate that an approach to shame based on mindfulness and acceptance appears to produce better treatment attendance and reduced substance use. PMID- 22040286 TI - Examining the stability of DSM-IV and empirically derived eating disorder classification: implications for DSM-5. AB - OBJECTIVE: The purpose of this investigation was to derive an empirical classification of eating disorder symptoms in a heterogeneous eating disorder sample using latent class analysis (LCA) and to examine the longitudinal stability of these latent classes (LCs) and the stability of DSM-IV eating disorder (ED) diagnoses. METHOD: A total of 429 females with ED symptoms were assessed using the Eating Disorder Examination every 6 months for 2 years. LCA was used to derive empirical classification at baseline. Latent transition analysis (LTA) was used to examine the longitudinal stability of LCs, and Markov modeling procedures were used to examine DSM-IV ED diagnoses over all the time points. RESULTS: LCA yielded a 3-class solution: binge eating and purging, binge eating only, and low body mass index. LTA indicated that these LCs showed greater stability over 2 years than DSM-IV diagnoses with the probability of remaining in the same class ranging from 0.69 to 0.91 for LCs and from 0.40 to 0.75 for DSM-IV diagnoses. Transition patterns also revealed more stability for LCs with only 21% changing classes compared with 63% of the DSM-IV diagnostic categories. CONCLUSION: Empirically derived classes of ED symptoms showed greater longitudinal stability than DSM-IV diagnoses over a 2-year time period, suggesting that modifying the criteria to be consistent with empirically based classification (e.g., reducing frequency requirements of binge eating and purging) may reduce ED diagnostic crossover in DSM-5. PMID- 22040287 TI - The role of phytochrome in stress tolerance. AB - It is well-documented that phytochromes can control plant growth and development from germination to flowering. Additionally, these photoreceptors have been shown to modulate both biotic and abiotic stress. This has led to a series of studies exploring the molecular and biochemical basis by which phytochromes modulate stresses, such as salinity, drought, high light or herbivory. Evidence for a role of phytrochromes in plant stress tolerance is explored and reviewed. PMID- 22040289 TI - Is a routine voiding cystourethrogram necessary in children after the first febrile urinary tract infection? AB - AIM: The aim of this study was to estimate the value of identifying vesicoureteral reflux (VUR) on a voiding cystourethrogram (VCUG) and the benefit of VUR management according to imaging strategies at the first febrile urinary tract infection (UTI). METHODS: Children aged 1-144 months (n = 618) with the first febrile UTI admitted at our hospital from 2000 to 2009 were enrolled. In all patients, renal sonogram (US), (99m) Tc-dimercaptosuccinic acid (DMSA) renal scanning and VCUG were performed. Retrospective analyses per patient and per renal unit were performed. RESULTS: Abnormal US or DMSA scans had a sensitivity of 100% and a negative predictive value (NPV) of 100% to detect high-grade reflux. In hydronephrotic kidneys, DMSA scanning had a sensitivity of 88.2% and a NPV of 97.1% to detect high-grade reflux. CONCLUSION: Routine VCUG is not required after the first febrile UTI in patients with normal US or normal DMSA scan. Even if the US reveals hydronephrosis, routine VCUG is not necessary if the DMSA findings are normal. It is recommended that children who did not receive both a DMSA scan and VCUG after the first febrile UTI should be followed up over the long term. PMID- 22040290 TI - Epilysin (matrix metalloproteinase-28) contributes to airway epithelial cell survival. AB - MMP28 is constitutively expressed by epithelial cells in many tissues, including the respiratory epithelium in the lung and keratinocytes in the skin. This constitutive expression suggests that MMP28 may serve a role in epithelial cell homeostasis. In an effort to determine its function in epithelial cell biology, we generated cell lines expressing wild-type or catalytically-inactive mutant MMP28 in two pulmonary epithelial cell lines, A549 and BEAS-2B. We observed that over-expression of MMP28 provided protection against apoptosis induced by either serum-deprivation or treatment with a protein kinase inhibitor, staurosporine. Furthermore, we observed increased caspase-3/7 activity in influenza-infected lungs from Mmp28-/- mice compared to wild-type mice, and this activity localized to the airway epithelium but was not associated with a change in viral load. Thus, we have identified a novel role of MMP28 in promoting epithelial cell survival in the lung. PMID- 22040291 TI - The SCO2 protein disulphide isomerase is required for thylakoid biogenesis and interacts with LHCB1 chlorophyll a/b binding proteins which affects chlorophyll biosynthesis in Arabidopsis seedlings. AB - The process of chloroplast biogenesis requires a multitude of pathways and processes to establish chloroplast function. In cotyledons of seedlings, chloroplasts develop either directly from proplastids (also named eoplasts) or, if germinated in the dark, via etioplasts, whereas in leaves chloroplasts derive from proplastids in the apical meristem and are then multiplied by division. The snowy cotyledon 2, sco2, mutations specifically disrupt chloroplast biogenesis in cotyledons. SCO2 encodes a chloroplast-localized protein disulphide isomerase, hypothesized to be involved in protein folding. Analysis of co-expressed genes with SCO2 revealed that genes with similar expression patterns encode chloroplast proteins involved in protein translation and in chlorophyll biosynthesis. Indeed, sco2-1 accumulates increased levels of the chlorophyll precursor, protochlorophyllide, in both dark grown cotyledons and leaves. Yeast two-hybrid analyses demonstrated that SCO2 directly interacts with the chlorophyll-binding LHCB1 proteins, being confirmed in planta using bimolecular fluorescence complementation (BIFC). Furthermore, ultrastructural analysis of sco2-1 chloroplasts revealed that formation and movement of transport vesicles from the inner envelope to the thylakoids is perturbed. SCO2 does not interact with the signal recognition particle proteins SRP54 and FtsY, which were shown to be involved in targeting of LHCB1 to the thylakoids. We hypothesize that SCO2 provides an alternative targeting pathway for light-harvesting chlorophyll binding (LHCB) proteins to the thylakoids via transport vesicles predominantly in cotyledons, with the signal recognition particle (SRP) pathway predominant in rosette leaves. Therefore, we propose that SCO2 is involved in the integration of LHCB1 proteins into the thylakoids that feeds back on the regulation of the tetrapyrrole biosynthetic pathway and nuclear gene expression. PMID- 22040292 TI - Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis. AB - BACKGROUND: The immature granulocyte count has been reported to be a marker of infection and sepsis. The difference in leukocyte subfractions (delta neutrophil index, DNI) in ADVIA 2120 reflects the fraction of circulating immature granulocytes in the blood. This study evaluated the clinical utility of DNI as a severity and prediction marker in critically ill patients with sepsis. METHODS: One hundred and three patients admitted to the medical intensive care unit with sepsis were studied. DNI (the difference in leukocyte subfractions identified by myeloperoxidase and nuclear lobularity channels) was determined using a specific blood cell analyzer. RESULTS: Forty four patients (42.7%) were diagnosed with severe sepsis/septic shock. Overt disseminated intravascular coagulation (DIC) occurred in 40 (38.8%). DNI was significantly higher in patients with severe sepsis/septic shock and overt DIC than in patients without (p < 0.05). DNI correlated with DIC score (r = 0.54, p < 0.001). We observed a monotonic increase in the proportion of overt DIC and severe sepsis/septic shock associated with increasing quartiles of DNI (p < 0.001). A DNI value > 6.5% was a better indicator of severe sepsis/septic shock than C-reactive protein, lactate, white blood cell count, and absolute neutrophil count (sensitivity, 81.3%; specificity, 91.0%; positive predictive value, 88.6%; and negative predictive value, 84.7%). In 36 (82%) of the 44 patients with severe sepsis/septic shock, DNI values were already elevated up to 12 hours before the onset of organ/circulatory failure. CONCLUSIONS: DNI may be used as a marker of disease severity in critically ill patients with sepsis. High levels of DNI may help to identify patients with an impending risk of developing severe sepsis/septic shock. PMID- 22040293 TI - Chemically doped random network carbon nanotube p-n junction diode for rectifier. AB - Semiconductors with higher carrier mobility and carrier density are required to fabricate a p-n junction diode for high-speed device operation and high-frequency signal processing. Here, we use a chemically doped semiconducting single-walled carbon nanotube (SWCNT) random network for a field effect transistor (FET) and demonstrate a rectifier operated at a wide range of frequencies by fabricating a p-n junction diode. The p-n diode was fabricated by using a pristine p-type SWCNT FET where half was covered by SiO(2) and the other half was chemically doped by using benzyl viologen molecules, which was converted into an n-type channel. The half-wave rectifier of the random network SWCNT p-n junction diode clearly highlights the device operation under high input signal frequencies up to 10 MHz with very low output distortion, which a commercial silicon p-n junction diode cannot access. These results indicate that the random network SWCNT p-n junction diodes can be used as building blocks of complex circuits in a range of applications in microelectronics, optoelectronics, sensors, and other systems. PMID- 22040294 TI - Default mode network in concussed individuals in response to the YMCA physical stress test. AB - We hypothesize that the evolution of mild traumatic brain injury (mTBI) may be related to differential effects of a concussive blow on the functional integrity of the brain default mode network (DMN) at rest and/or in response to physical stress. Accordingly, in this resting-state functional magnetic resonance imaging (fMRI) study, we examined 14 subjects 10+/-2 days post-sports-related mTBI and 15 age-matched normal volunteers (NVs) to investigate the possibility that the integrity of the DMN is disrupted at the resting state and/or following the physical stress test. First, all mTBI subjects were asymptomatic based upon clinical evaluation and neuropsychological (NP) assessments prior to the MRI session. Second, the functional integrity within the DMN, a main resting-state network, remained resilient to a single concussive blow. Specifically, the major regions of interest (ROIs) constituting the DMN (e.g., the posterior cingulate cortex [PCC]/precuneus area, the medial prefrontal cortex [MPFC], and left and right lateral parietal cortices [LLP and RLP]) and the connectivity within these four ROIs was similar between NVs and mTBI subjects prior to the YMCA physical stress test. However, the YMCA physical stress test disrupted the DMN, significantly reducing the magnitude of the connection between the PCC and left lateral parietal ROI, and PCC and right lateral parietal ROI, as well as between the PCC and MPFC in mTBI subjects. Thus while the DMN remained resilient to a single mTBI without exertion at 10 days post-injury, it was altered in response to limited physical stress. This may explain some clinical features of mTBI and provide some insight into its mechanism. This important finding should be considered by clinical practitioners when making decisions regarding return-to play and clearing mTBI athletes for sports participation. PMID- 22040295 TI - Direct synthesis and characterization of optically transparent conformal zinc oxide nanocrystalline thin films by rapid thermal plasma CVD. AB - We report a rapid, self-catalyzed, solid precursor-based thermal plasma chemical vapor deposition process for depositing a conformal, nonporous, and optically transparent nanocrystalline ZnO thin film at 130 Torr (0.17 atm). Pure solid zinc is inductively heated and melted, followed by ionization by thermal induction argon/oxygen plasma to produce conformal, nonporous nanocrystalline ZnO films at a growth rate of up to 50 nm/min on amorphous and crystalline substrates including Si (100), fused quartz, glass, muscovite, c- and a-plane sapphire (Al2O3), gold, titanium, and polyimide. X-ray diffraction indicates the grains of as-deposited ZnO to be highly textured, with the fastest growth occurring along the c-axis. The individual grains are observed to be faceted by (103) planes which are the slowest growth planes. ZnO nanocrystalline films of nominal thicknesses of 200 nm are deposited at substrate temperatures of 330 degrees C and 160 degrees C on metal/ceramic substrates and polymer substrates, respectively. In addition, 20-nm- and 200-nm-thick films are also deposited on quartz substrates for optical characterization. At optical spectra above 375 nm, the measured optical transmittance of a 200-nm-thick ZnO film is greater than 80%, while that of a 20-nm-thick film is close to 100%. For a 200-nm-thick ZnO film with an average grain size of 100 nm, a four-point probe measurement shows electrical conductivity of up to 910 S/m. Annealing of 200-nm-thick ZnO films in 300 sccm pure argon at temperatures ranging from 750 degrees C to 950 degrees C (at homologous temperatures between 0.46 and 0.54) alters the textures and morphologies of the thin film. Based on scanning electron microscope images, higher annealing temperatures appear to restructure the ZnO nanocrystalline films to form nanorods of ZnO due to a combination of grain boundary diffusion and bulk diffusion.PACS: films and coatings, 81.15.-z; nanocrystalline materials, 81.07.Bc; II-VI semiconductors, 81.05.Dz. PMID- 22040296 TI - Physiologic effect and safety of the pumpless extracorporeal interventional lung assist system in patients with acute respiratory failure--a pilot study. AB - Interventional lung assist (iLA) effectively reduces CO(2) tension and permits protective lung ventilation in patients with acute respiratory distress syndrome. However, there is little experience in using iLA in acute respiratory failure from various causes and no experience for small body sizes such as Asian patients. We evaluated the physiologic effect and safety of the iLA device in patients with acute respiratory failure from various causes. We enrolled 11 consecutive patients with severe respiratory failure from various causes. Wire enforced cannulae (13-15 Fr) were inserted under ultrasound guidance and connected to iLA. Arterial blood gas analysis, ventilator parameters, hemodynamic parameter, and adverse events were recorded serially. During the first 24h of iLA use, mean blood flow was 1.08+/-0.15L/min, PaCO(2) decreased from 83.9+/-23.4mmHg to 40.7+/-10.2mmHg, and PaO(2) /FiO(2) ratio increased from 110+/-37 to 141+/-74. Minute ventilation decreased from 9.4+/-2.5 to 6.3+/-1.5L/min, and peak inspiratory pressure decreased from 30.3+/-7.1cm H(2) O to 28.8+/-9.4cm H(2) O. No serious adverse events were observed during iLA use. iLA showed effective CO(2) removal, allowed for reducing the invasiveness of mechanical ventilation in patients with severe respiratory failure from various causes even using a small sized catheter and was safe in small body-sized patients. PMID- 22040297 TI - Rank-based ant system method for non-linear QSPR analysis: QSPR studies of the solubility parameter. AB - The solubility parameter (delta) plays a unique role in the development of stable pharmaceutical formulations for assessing phase segregation during product synthesis. Understanding this parameter helps to determine how a drug substance will behave when processed or when dosed in vivo. The aim of this work was to develop a novel comprehensive yet rapid and accurate Quantitative Structure Property Relationship (QSPR) method based on the rank-based ant system feature selection. The method was coupled with the multiple linear regression and support vector regression and applied to the assessment of solubility parameters for a diverse dataset of 1804 chemical compounds. The models were validated by solubility prediction of 360 test set compounds which were not used in building models. The developed models have high prediction power characterized by r (2) values 0.75 and 0.82, and RMSE values 1.96 and 1.65 (J/(cm(3)))(0.5) for the external test set. Various validation techniques and comparison results with the novel optimized support vector regression indicate that the developed models can be used to determine the solubility parameters for a diverse set of chemicals with an acceptable accuracy. The developed models can be beneficial for designing new chemical materials with desired solubility parameter values. PMID- 22040298 TI - The association between maternal serious psychological distress and child obesity at 3 years: a cross-sectional analysis of the UK Millennium Cohort Data. AB - BACKGROUND: The prevalence of child obesity is increasing rapidly worldwide. Early childhood has been identified as a critical time period for the development of obesity. Maternal mental health and early life environment are crucial factors and have been linked to adverse child outcomes. The objective of the study was to examine the relationship between maternal serious psychological distress and obesity in early childhood. METHODS: A cross-sectional analysis of data from the Millennium Cohort Study was conducted. Subjects consisted of all natural mothers (n= 10 465) who had complete and plausible data for Kessler-6 scores, socio-demographic and anthropometric variables, and their children for whom anthropometric measurements were completed at age 3. Maternal serious psychological distress was defined as a score of 13 or more on the Kessler-6 scale. Obesity was defined as body mass index >=95th centile of the 1990 reference chart for age and sex in children. The data were analysed using spss 16. Maternal socio-demographic factors that are known to influence maternal mental health and child obesity were identified and adjusted using multivariate logistic regression. RESULTS: Of the 10 465 mother-child dyads, 3.5% of mothers had serious psychological distress and 5.5% of children were obese at 3 years of age. Logistic regression analysis showed that maternal serious psychological distress was associated with early childhood obesity (P= 0.01; OR 1.62, 95% CI 1.11, 2.37). After adjusting for potential confounding factors using multivariate logistic regression, maternal serious psychological distress remained significantly associated with early childhood obesity (P= 0.01; OR 1.59, 95% CI 1.08, 2.34). CONCLUSIONS: The results show that maternal serious psychological distress is independently associated with early childhood obesity. PMID- 22040299 TI - Metabolomic screening and identification of the bioactivation pathways of ritonavir. AB - Ritonavir-boosted protease inhibitor regimens are widely used for HIV chemotherapy. However, ritonavir causes multiple side effects, and the mechanisms are not fully understood. The current study was designed to explore the metabolic pathways of ritonavir that may be related to its toxicity. Metabolomic analysis screened out 26 ritonavir metabolites in mice, and half of them are novel. These novel ritonavir metabolites include two glycine conjugated, two N-acetylcysteine conjugated, and three ring-open products. Accompanied with the generation of ritonavir ring-open metabolites, the formation of methanethioamide and 2 methylpropanethioamide were expected. Upon the basis of the structures of these novel metabolites, five bioactivation pathways are proposed, which may be associated with sulfation and epoxidation. By using Cyp3a-null mice, we confirmed that CYP3A is involved in four pathways of RTV bioactivation. In addition, all these five bioactivation pathways were recapitulated in the incubation of ritonavir in human liver microsomes. Further studies are suggested to determine the role of CYP3A and these bioactivation pathways in ritonavir toxicity. PMID- 22040300 TI - Revisiting the dispersion mechanism of grafted nanoparticles in polymer matrix: a detailed molecular dynamics simulation. AB - By focusing on the grafted nanoparticles (NPs) embedded in polymer melts, a detailed coarse-grained molecular dynamics simulation is adopted to investigate the effects of the grafting density, the length of the matrix and grafted chains on the dispersion of the NPs. We have employed visualization snapshots, radial distribution functions (RDFs), the interaction energy between NPs, the number of neighbor NPs, and the conformation of the brush chains to clearly analyze the dispersion state of the grafted NPs. Our simulated results generally indicate that the dispersion of the NPs is controlled by both the excluded volume of the grafted NPs and the interface between the brushes and the matrix. It is found that increasing grafting density or grafted chain length leads to better dispersion, owing to larger excluded volume; however, increasing the length of the matrix chains leads to aggregation of NPs, attributed to both a progressive loss of the interface between the brushes and the matrix and the overlap between brushes of different NPs, intrinsically driven by entropy. Meanwhile, it is found that there exists an optimum grafting density (sigma(c)) for the dispersion of the NPs, which roughly obeys the following mathematical relation: sigma(c) is proportional to N(m)(K)/N(g)(L), where K, L > 0 and N(m) and N(g) represent the length of the matrix and grafted chain length, respectively. Considering the practical situation that the grafted brushes and the matrix polymer are mostly not chemically identical, we also studied the effect of the compatibility between the brushes and the matrix polymer by taking into account the attraction between the grafted chains and the matrix chains. In general, our comprehensive simulation results are believed to guide the design and preparation of high performance polymer nanocomposites with good or even tailored dispersion of NPs. PMID- 22040302 TI - Four cases of subepidermal calcified nodule on a child's sole. PMID- 22040301 TI - Development of a 3D immersive videogame to improve arm-postural coordination in patients with TBI. AB - BACKGROUND: Traumatic brain injury (TBI) disrupts the central and executive mechanisms of arm(s) and postural (trunk and legs) coordination. To address these issues, we developed a 3D immersive videogame--Octopus. The game was developed using the basic principles of videogame design and previous experience of using videogames for rehabilitation of patients with acquired brain injuries. Unlike many other custom-designed virtual environments, Octopus included an actual gaming component with a system of multiple rewards, making the game challenging, competitive, motivating and fun. Effect of a short-term practice with the Octopus game on arm-postural coordination in patients with TBI was tested. METHODS: The game was developed using WorldViz Vizard software, integrated with the Qualysis system for motion analysis. Avatars of the participant's hands precisely reproducing the real-time kinematic patterns were synchronized with the simulated environment, presented in the first person 3D view on an 82-inch DLP screen. 13 individuals with mild-to-moderate manifestations of TBI participated in the study. While standing in front of the screen, the participants interacted with a computer-generated environment by popping bubbles blown by the Octopus. The bubbles followed a specific trajectory. Interception of the bubbles with the left or right hand avatar allowed flexible use of the postural segments for balance maintenance and arm transport. All participants practiced ten 90-s gaming trials during a single session, followed by a retention test. Arm-postural coordination was analysed using principal component analysis. RESULTS: As a result of the short-term practice, the participants improved in game performance, arm movement time, and precision. Improvements were achieved mostly by adapting efficient arm postural coordination strategies. Of the 13 participants, 10 showed an immediate increase in arm forward reach and single-leg stance time. CONCLUSION: These results support the feasibility of using the custom-made 3D game for retraining of arm-postural coordination disrupted as a result of TBI. PMID- 22040303 TI - Role of ligand to control the mechanism of nitric oxide reduction of copper(II) complexes and ligand nitrosation. AB - The nitric oxide reactivity of two copper(II) complexes, 1 and 2 with ligands L(1) and L(2), respectively, [L(1) = 5,5,7,12,12,14-hexamethyl-1,4,8,11 tetraazacyclotetradecane, L(2) = 5,5,7-trimethyl-[1,4]-diazepane] have been studied. The copper(II) center in complex 1 was found to be unreactive toward nitric oxide in pure acetonitrile; however, it displayed reduction in methanol solvent in presence of base. The copper(II) center in 2, in acetonitrile solvent, on exposure to nitric oxide has been found to be reduced to copper(I). The same reduction was observed in methanol, also, in case of complex 2. In case of complex 1, presumably, the attack of nitric oxide on the deprotonated amine is the first step, followed by electron transfer to the copper(II) center to afford the reduction. Alternatively, first NO coordination to the Cu(II) followed by NO(+) migration to the secondary amine is the most probable in case of complex 2. The observation of the transient intermediate in UV-visible and FT-IR spectroscopy prior to reduction in case of complex 2 also supports this possibility. In both cases, the reduction resulted into N-nitrosation; in 1, only mononitrosation was observed whereas complex 2 afforded dinitrosation as major product along with a minor amount of mononitrosation. Thus, it is evident from the present study that the macrocyclic ligands prefer the deprotonation pathway leading to mononitrosation; whereas nonmacrocyclic ones prefer the [Cu(II)-NO] intermediate pathway resulting into nitrosation at all the available sites of the ligand as major product. PMID- 22040304 TI - Inhibitory effect of intravitreal injection of bevacizumab on nerve growth factor. AB - PURPOSE: To investigate the inhibitory effect of intravitreal injection of bevacizumab on the expression of nerve growth factor (NGF) in rabbit retina. METHODS: The right eyes of 40 New Zealand white rabbits were injected with 1.25 mg (0.05 cc) bevacizumab three times monthly; as controls, the left eyes received sham injections. Apoptosis in retinal cells was evaluated by immunohistochemical staining for caspase-3, and by in situ terminal deoxynucleotidyl transferase mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments. NGF and vascular endothelial growth factor (VEGF) proteins in rabbit retinas were measured quantitatively (Enzyme linked immunosorbent assay (ELISA)) and qualitatively (immunohistochemical staining) 1 and 4 months after injection. NGF and VEGF messenger RNAs in rabbit retinas were evaluated by real-time polymerase chain reaction (RT-PCR). RESULTS: As shown by the TUNEL assay and caspase-3 immunostaining, the bevacizumab-injected group had significantly more apoptotic activity than did the control group. Levels of retinal NGF and VEGF proteins in the bevacizumab group were lower than those in the control group (p < 0.05). Immunohistochemical staining of NGF and VEGF was weaker in the bevacizumab group than in the control group. NGF and VEGF mRNA levels in the bevacizumab group were lower than those of the control group (p < 0.05). CONCLUSIONS: Findings of the present study suggest that apoptosis in retinal cells after intravitreal bevacizumab injection is increased by down-regulated NGF, caused by VEGF inhibition in rabbits. PMID- 22040306 TI - Risk assessment of methyl-mercury intake through cephalopods consumption in Portugal. AB - The intake of methyl-mercury (methyl-Hg) through the consumption of three common cephalopod species, cuttlefish (Sepia officinalis), squid (Loligo vulgaris) and octopus (Octopus vulgaris), in Portugal as well as the associated probability of exceeding the provisional tolerable weekly intake (PTWI) were estimated by combining methyl-Hg contamination levels in these three cephalopods with constructed consumption scenarios and with a hypothesised consumption distribution for the general Portuguese population. It was found that squid presents no serious health concern with respect to methyl-Hg, but cuttlefish and octopus consumption should not exceed two 150 g meals per week. Moreover, the methyl-Hg risk assessment for Portuguese consumers showed no risk concerning the observed cephalopods consumption levels. However, besides methyl-Hg, other toxic metals present in cephalopods, such as cadmium, may be a serious health concern and the methyl-Hg risk can be compounded by the risk of other foods containing significant methyl-Hg levels, especially long-lived sea predators. Accordingly, a cautionary note must be attached to advised maximum consumptions, which may be revised by future studies. Tail estimation (TE) estimator was more accurate for lower probabilities, rendering accurate risk estimations different from zero. However, for higher probabilities, the much simpler plug-in (PI) estimator could be applied. Additionally, limitations of a deterministic approach were identified. PMID- 22040305 TI - Aeromonas salmonicida-secreted protein AopP is a potent inducer of apoptosis in a mammalian and a Drosophila model. AB - Some pathogens are able to establish themselves within the host because they have evolved mechanisms to disrupt host innate immunity. For example, a number of pathogens secrete preformed effector proteins via type III secretion apparatuses that influence innate immune or apoptotic signalling pathways. One group of effector proteins that usurp innate immune signalling is the YopJ-like family of bacterial effector proteins, which includes AopP from Aeromonas salmonicida. Aeromonas species are known to cause gastrointestinal disease in humans, and are associated mainly with subcutaneous wound infections and septicaemia in other metazoans, particularly fish. AopP has been reported to have inhibitory activity against the NF-kappaB pathway in cultured cells, although the pathological outcomes of AopP activity have not been examined. Here, we show that AopP has potent pro-apoptotic activity when expressed in cultured mammalian macrophage or epithelial cells, or when ectopically expressed in Drosophila melanogaster haemocytes or imaginal disk epithelial cells. Furthermore, apoptosis was significantly elevated upon concurrent AopP expression and TNF-alpha cellular stimulation. Together, our results demonstrate how the specificity of a YopJ-like protein towards signalling pathways directly governs cellular pathological outcome in disease. PMID- 22040307 TI - A pharmacist-led intervention for increasing the uptake of Home Medicines Review (HMR) among residents of retirement villages (PHARMER): protocol for a cluster randomised controlled trial. AB - BACKGROUND: The majority of retirement village residents are at risk of medication misadventure. In a recent survey of retirement village residents in Victoria, two-thirds had at least one medication-related risk factor, and hence were eligible to receive a government-subsidised Home Medicines Review (HMR). However, only 6% of eligible residents had received a HMR in the previous 12 months. Reasons for the poor uptake of HMR, and interventions for improving HMR uptake, have been identified and developed with input from stakeholders. The trial will test the effect of Pharmacist-conducted HMR to Address the Risk of Medication-related Events in Retirement Villages (PHARMER) in improving the uptake of HMRs among retirement village residents. METHODS/DESIGN: This is a multicentre prospective cluster randomised controlled trial. Ten retirement villages in Victoria, Australia will be recruited for this trial. Retirement villages will be selected in consultation with the Residents of Retirement Villages Victoria Inc. (RRVV), based on geographical locations (e.g. northeast or southwest), size and other factors. Residents from selected villages will be recruited with the help of RRVV Resident Liaison Officers using a range of strategies. Randomisation will be by geographical location to minimise contamination. Participating villages and residents will be allocated to either Pharmacist Intervention Group (PIG) or Usual Care Group (UCG). Each group will include five retirement villages and will have at least 77 residents in total. The intervention (PHARMER) comprises educating residents regarding HMR, and using a risk assessment checklist by residents to notify their General Practitioners of their medication risk. Uptake of HMR and medication adherence will be assessed in both PIG and UCG at three and six months using telephone interviews and questionnaires. DISCUSSION: This study is the first to develop and test an intervention to improve the uptake of HMR among Australian residents in retirement villages, with a view to decreasing medication risk. A multi-faceted interventional approach will be used as suggested by stakeholders. The trial is expected to be complete by late 2011 and results will be available in 2012. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12611000109909). PMID- 22040308 TI - Functional MRI and motor behavioral changes obtained with constraint-induced movement therapy in chronic stroke. AB - BACKGROUND: The clinical benefits of intensive stroke rehabilitation vary individually. We used multimodal functional imaging to assess the relationship of clinical gain and imaging changes in patients with chronic stroke whose voluntary motor control improved after constraint-induced movement therapy (CIMT). METHODS: Eleven patients (37.6 +/- 36.8 months from stroke) were studied by functional MRI (fMRI), transcranial magnetic stimulation (TMS), and behavioral assessment of hand motor control (Wolf Motor Function Test) before and after 2 weeks of CIMT. Individual and group-level changes in imaging and behavioral parameters were investigated. RESULTS: Increase in fMRI activation in the sensorimotor areas was greater amongst those subjects who had poor hand motor behavior before therapy and/or whose motor behavior improved notably because of therapy than amongst subjects with relatively good motor behavior already before therapy. The magnitude of CIMT-induced changes in task-related fMRI activation differed between lesioned and non-lesioned hemispheres, and the fMRI laterality index was different for paretic and non-paretic hand tasks. The corticospinal conduction time in TMS was significantly decreased after CIM therapy. CONCLUSIONS: Alterations in sensorimotor cortical activations (fMRI) and corticospinal conductivity (TMS) were observed after intensive rehabilitation in patients with chronic stroke. Activation and functional changes in fMRI and TMS correlated significantly with the degree of clinical improvement in hand motor behavior. The present data advance the understanding of the functional underpinnings of motor recovery, which may be obtained even years after the stroke. PMID- 22040309 TI - Fatigue and fracture resistance of zirconia crowns prepared with different finish line designs. AB - PURPOSE: The aim of this study was to evaluate the effect of finish line design on the fatigue, fracture resistance, and failure type of veneered zirconia restorations. MATERIALS AND METHODS: A CAD/CAM system (Cercon) was used to prepare zirconia frameworks (0.5 mm thick) for a maxillary central incisor. Three finish line designs were evaluated: a complete narrow chamfer, a narrow chamfer with a lingual ledge, and a complete ledge. The prepared frameworks were veneered using a press-on ceramic (Ceram Press) and were cemented on the corresponding prepared teeth using a resin cement (Panavia F2.0). The cemented specimens were thermocycled, subjected to dynamic fatigue, and finally loaded till fracture. Fractured specimens were examined under a scanning electron microscope to assess fracture type. One-way ANOVA and Bonferroni post hoc tests were used to analyze the data (alpha= 0.05). RESULTS: The finish line design did not have any significant statistical influence on the fracture resistance (F = 1.9, p= 0.346) or on the failure type of the tested specimens. Adjusted R squared value (R = 0.049) indicated a weak correlation between finish line design and fracture load of the tested specimens. All specimens failed due to cracking and fracture of the veneer ceramic. Meanwhile, the framework remained entirely intact. Three narrow chamfer finish line specimens demonstrated adhesive fracture of the veneer ceramic during dynamic fatigue testing, related to overextension of the veneer ceramic during the layering procedure. CONCLUSION: Within the limitations of this study, the finish line design did not influence the fatigue or the fracture resistance of veneered zirconia crowns. Selection of any of the finish line designs should be based on the clinical condition of the restored tooth. PMID- 22040310 TI - Stable carbon and nitrogen isotope ratios of sodium and potassium cyanide as a forensic signature. AB - Sodium and potassium cyanide are highly toxic, produced in large amounts by the chemical industry, and linked to numerous high-profile crimes. The U.S. Centers for Disease Control and Prevention has identified cyanide as one of the most probable agents to be used in a chemical terrorism event. We investigated whether stable C and N isotopic content of sodium and potassium cyanide could serve as a forensic signature for sample matching, using a collection of 65 cyanide samples. Upon analysis, a few of the cyanide samples displayed nonhomogeneous isotopic content associated with degradation to a carbonate salt and loss of hydrogen cyanide. Most samples had highly reproducible isotope content. Of the 65 cyanide samples, >95% could be properly matched based on C and N isotope ratios, with a false match rate <3%. These results suggest that stable C and N isotope ratios are a useful forensic signature for matching cyanide samples. PMID- 22040311 TI - Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial. AB - AIM: To compare the incidence of hyponatremia in full-term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET). METHODS: In this double-blind, randomized, controlled trial, full-term newborns (>=37 weeks), appropriate for gestational age, with severe non haemolytic hyperbilirubinemia (serum bilirubin >= 20 mg/dL) were enrolled. Eligible neonates were randomized to receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5% dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary outcome was proportion of neonates developing hyponatremia (serum Na < 135 mmol/L) after 8 h. RESULTS: Forty-two neonates were analysed in each group. Proportion of neonates developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to isotonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was similar in both groups. CONCLUSION: In full-term neonates with severe hyperbilirubinemia, administration of hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia while isotonic fluid was associated with an increased incidence of hypernatremia. PMID- 22040312 TI - Early puzzle play: a predictor of preschoolers' spatial transformation skill. AB - Individual differences in spatial skill emerge prior to kindergarten entry. However, little is known about the early experiences that may contribute to these differences. The current study examined the relation between children's early puzzle play and their spatial skill. Children and parents (n = 53) were observed at home for 90 min every 4 months (6 times) between 2 and 4 years of age (26 to 46 months). When children were 4 years 6 months old, they completed a spatial task involving mental transformations of 2-dimensional shapes. Children who were observed playing with puzzles performed better on this task than those who did not, controlling for parent education, income, and overall parent word types. Moreover, among those children who played with puzzles, frequency of puzzle play predicted performance on the spatial transformation task. Although the frequency of puzzle play did not differ for boys and girls, the quality of puzzle play (a composite of puzzle difficulty, parent engagement, and parent spatial language) was higher for boys than for girls. In addition, variation in puzzle play quality predicted performance on the spatial transformation task for girls but not for boys. Implications of these findings as well as future directions for research on the role of puzzle play in the development of spatial skill are discussed. PMID- 22040313 TI - Academic adjustment across middle school: the role of public regard and parenting. AB - In the current longitudinal study, we examined associations between Black and Latino youths' perceptions of the public's opinion of their racial/ethnic group (i.e., public regard) and changes in academic adjustment outcomes across middle school. We also tested combinations of racial/ethnic socialization and parent involvement in academic activities as moderators of this association. We used a 2nd-order latent trajectory model to test changes in academic adjustment outcomes in a sample of 345 Black and Latino urban youth across 6th, 7th, and 8th grades (51% female). Results revealed a significant average linear decline in academic adjustment from 6th to 8th grade, as well as significant variation around this decline. We found that parenting moderated the association between public regard and the latent trajectory of academic adjustment. Specifically, for youth who reported high racial/ethnic socialization and low parent academic involvement, lower public regard predicted lower academic adjustment in 6th grade. For youth who reported both low racial/ethnic socialization and low parent academic involvement, lower public regard predicted a steeper decline in academic adjustment over time. Finally, among youth who reported high racial/ethnic socialization and high parent academic involvement, public regard was not associated with either the intercept or the slope of academic adjustment. Thus, the combination of high racial/ethnic socialization and parent academic involvement may protect youths' academic motivation and performance from the negative effects of believing the public has low opinions of one's racial/ethnic group. Implications for protecting Black and Latino youths' academic outcomes from decline during middle school are discussed. PMID- 22040314 TI - Three-year-olds understand appearance and reality--just not about the same object at the same time. AB - Young children struggle in the classic tests of appearance versus reality. In the current Study 1, 3-year-olds had to determine which of 2 objects (a deceptive or a nondeceptive one) an adult requested when asking for the "real X" versus "the one that looks like X." In Study 2, children of the same age had to indicate what a single deceptive object (e.g., a chocolate-eraser) looked like and what it really was by selecting one of two items that represented this object's appearance (a chocolate bar) or identity (a regular eraser). Children were mainly successful in Study 1 but not in Study 2. The findings are discussed with a focus on young children's difficulty with "confronting" perspectives, which may be involved in their struggles with a number of classic theory of mind tasks. PMID- 22040315 TI - A longitudinal study of the association between violent video game play and aggression among adolescents. AB - In the past 2 decades, correlational and experimental studies have found a positive association between violent video game play and aggression. There is less evidence, however, to support a long-term relation between these behaviors. This study examined sustained violent video game play and adolescent aggressive behavior across the high school years and directly assessed the socialization (violent video game play predicts aggression over time) versus selection hypotheses (aggression predicts violent video game play over time). Adolescents (N = 1,492, 50.8% female) were surveyed annually from Grade 9 to Grade 12 about their video game play and aggressive behaviors. Nonviolent video game play, frequency of overall video game play, and a comprehensive set of potential 3rd variables were included as covariates in each analysis. Sustained violent video game play was significantly related to steeper increases in adolescents' trajectory of aggressive behavior over time. Moreover, greater violent video game play predicted higher levels of aggression over time, after controlling for previous levels of aggression, supporting the socialization hypothesis. In contrast, no support was found for the selection hypothesis. Nonviolent video game play also did not predict higher levels of aggressive behavior over time. Our findings, and the fact that many adolescents play video games for several hours every day, underscore the need for a greater understanding of the long-term relation between violent video games and aggression, as well as the specific game characteristics (e.g., violent content, competition, pace of action) that may be responsible for this association. PMID- 22040316 TI - Hydride as a leaving group in the reaction of pinacolborane with halides under ambient Grignard and Barbier conditions. One-pot synthesis of alkyl, aryl, heteroaryl, vinyl, and allyl pinacolboronic esters. AB - Grignard reagents (aliphatic, aromatic, heteroaromatic, vinyl, or allylic) react with 1 equiv of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (pinacolborane, PinBH) at ambient temperature in tetrahydrofuran (THF) to afford the corresponding pinacolboronates. The initially formed dialkoxy alkylborohydride intermediate quickly eliminates hydridomagnesium bromide (HMgBr) and affords the product boronic ester in very good yield. Hydridomagnesium bromide (HMgBr) in turn disproportionates to a 1:1 mixture of magnesium hydride (MgH(2)) and magnesium bromide (MgBr(2)) on addition of pentane to the reaction mixture. DFT calculations (Gaussian09) at the B3LYP/6-31G(d) level of theory show that disproportionation of HMgBr to MgH(2) and MgBr(2) is viable in the coordinating ethereal solvents. This reaction also can be carried out under Barbier conditions, where the neat PinBH is added to the flask prior to the in situ formation of Grignard reagent from the corresponding organic halide and magnesium metal. Pinacolboronic ester synthesis under Barbier conditions does not give Wurtz coupling side products from reactive halides, such as benzylic and allylic halides. The reaction between PinBH and various Grignard reagents is an efficient, mild, and general method for the synthesis of pinacolboronates. PMID- 22040317 TI - Assessment of a tissue-engineered gastric wall patch in a rat model. AB - Stenosis or deformity of the remaining stomach can occur after gastrectomy and result in stomach malfunction. The objective of this study is to demonstrate the feasibility of transplanting a tissue-engineered gastric wall patch in a rat model to alleviate the complications after resection of a large area of the gastric wall. Tissue-engineered gastric wall patches were created from gastric epithelial organoid units and biodegradable polymer scaffolds. In the first treatment group, gastric wall defects were created in recipient rats and covered with fresh tissue-engineered gastric wall patches (simultaneous transplantation). In the second treatment group, the tissue-engineered gastric wall patches were frozen for 12weeks, and then transplanted in recipient rats (metachronous transplantation). Tissue-engineered gastric wall patches were successfully used as a substitute of the resected native gastric wall in both simultaneous and metachronous transplantation groups. The defrosted wall patches showed almost the same cell viability as the fresh ones. Twenty-four weeks after transplantation, the defect in the gastric wall was well-covered with tissue-engineered gastric wall patch, and the repaired stomach showed no deformity macroscopically in both groups. Histology showed continuous mucosa and smooth muscle layers at the tissue engineered stomach wall margin. The feasibility of transplanting a tissue engineered patch to repair a defect in the native gastric wall has been successfully shown in a rat model, thereby taking one step closer toward the transplantation of an entire tissue-engineered stomach in the future. PMID- 22040318 TI - Sporadic fatal insomnia in a young woman: a diagnostic challenge: case report. AB - BACKGROUND: Sporadic fatal insomnia (sFI) and fatal familial insomnia (FFI) are rare human prion diseases. CASE PRESENTATION: We report a case of a 33-year-old female who died of a prion disease for whom the diagnosis of sFI or FFI was not considered clinically. Following death of this patient, an interview with a close family member indicated the patient's illness included a major change in her sleep pattern, corroborating the reported autopsy diagnosis of sFI. Genetic tests identified no prion protein (PrP) gene mutation, but neuropathological examination and molecular study showed protease-resistant PrP (PrPres) in several brain regions and severe atrophy of the anterior-ventral and medial-dorsal thalamic nuclei similar to that described in FFI. CONCLUSIONS: In patients with suspected prion disease, a characteristic change in sleep pattern can be an important clinical clue for identifying sFI or FFI; polysomnography (PSG), genetic analysis, and nuclear imaging may aid in diagnosis. PMID- 22040319 TI - The myth of participation in occupational therapy: reconceptualizing a client centred approach. AB - Participation is often the comprehensive objective of treatment but also an indication of the extent to which the process of occupational therapy is client centred. The purpose of this study was to explore levels of participation during occupational therapy among clients in the area of mental health from the occupational therapists' perspectives. Additionally the authors sought to identify factors that might hinder client participation. Postal questionnaires were sent out to 670 Swedish occupational therapists working with persons with mental illness and learning disabilities. The questionnaire required therapists to rate clients' levels of participation during occupational therapy. Findings indicated that the most common level of participation for the clients was interdependent, meaning that problems, goals, and plans were identified jointly and collaboratively with the occupational therapist. However, more than 20% of the clients were described as being dependent. Almost 90% of the occupational therapists rated client participation in therapy to be very important and nearly 70% claimed that client participation in general needed to be increased. Occupational therapists rated the primary barriers to participation as being clients' inability to participate and organizational and financial problems. Implications of these findings for education in client-centred practice approaches are discussed. PMID- 22040320 TI - 3-(3-amino-3-carboxypropyl)-5,6-dihydrouridine is one of two novel post transcriptional modifications in tRNALys(UUU) from Trypanosoma brucei. AB - tRNA is the most heavily modified of all RNA types, with typically 10-20% of the residues being post-transcriptionally altered. Unravelling the modification pattern of a tRNA is a challenging task; there are 92 currently known tRNA modifications, many of which are chemically similar. Furthermore, the tRNA has to be investigated with single-nucleotide resolution in order to ensure complete mapping of all modifications. In the present work, we characterized tRNA(Lys)(UUU) from Trypanosoma brucei, and provide a complete overview of its post-transcriptional modifications. The first step was MALDI-TOF MS of two independent digests of the tRNA, with RNase A and RNase T1, respectively. This revealed digestion products harbouring mass-changing modifications. Next, the modifications were mapped at the nucleotide level in the RNase products by tandem MS. Comparison with the sequence of the unmodified tRNA revealed the modified residues. The modifications were further characterized at the nucleoside level by chromatographic retention time and fragmentation pattern upon higher-order tandem MS. Phylogenetic comparison with modifications in tRNA(Lys) from other organisms was used through the entire analysis. We identified modifications on 12 nucleosides in tRNA(Lys)(UUU), where U47 exhibited a novel modification, 3-(3 amino-3-carboxypropyl)-5,6-dihydrouridine, based on identical chromatographic retention and MS fragmentation as the synthetic nucleoside. A37 was observed in two versions: a minor fraction with the previously described 2-methylthio-N(6) threonylcarbamoyl-modification, and a major fraction with A37 being modified by a 294.0-Da moiety. The latter product is the largest adenosine modification reported so far, and we discuss its nature and origin. PMID- 22040321 TI - Control over self-assembly of diblock copolymers on hexagonal and square templates for high area density circuit boards. AB - Self-assembled diblock copolymer melts on patterned substrates can induce a smaller characteristic domain spacing compared to predefined lithographic patterns and enable the manufacture of circuit boards with a high area density of computing and storage units. Monte Carlo simulation using coarse-grain models of polystyrene-b-polydimethylsiloxane shows that the generation of high-density hexagonal and square patterns is controlled by the ratio N(D) of the surface area per post and the surface area per spherical domain of neat block copolymer. N(D) represents the preferred number of block copolymer domains per post. Selected integer numbers support the formation of ordered structures on hexagonal (1, 3, 4, 7, 9) and square (1, 2, 5, 7) templates. On square templates, only smaller numbers of block copolymer domains per post support the formation of ordered arrays with significant stabilization energies relative to hexagonal morphology. Deviation from suitable integer numbers N(D) increases the likelihood of transitional morphologies between square and hexagonal. Upon increasing the spacing of posts on the substrate, square arrays, nested square arrays, and disordered hexagonal morphologies with multiple coordination numbers were identified, accompanied by a decrease in stabilization energy. Control over the main design parameter N(D) may allow an up to 7-fold increase in density of spherical block copolymer domains per surface area in comparison to the density of square posts and provide access to a wide range of high-density nanostructures to pattern electronic devices. PMID- 22040322 TI - MolabIS--an integrated information system for storing and managing molecular genetics data. AB - BACKGROUND: Long-term sample storage, tracing of data flow and data export for subsequent analyses are of great importance in genetics studies. Therefore, molecular labs do need a proper information system to handle an increasing amount of data from different projects. RESULTS: We have developed a molecular labs information management system (MolabIS). It was implemented as a web-based system allowing the users to capture original data at each step of their workflow. MolabIS provides essential functionality for managing information on individuals, tracking samples and storage locations, capturing raw files, importing final data from external files, searching results, accessing and modifying data. Further important features are options to generate ready-to-print reports and convert sequence and microsatellite data into various data formats, which can be used as input files in subsequent analyses. Moreover, MolabIS also provides a tool for data migration. CONCLUSIONS: MolabIS is designed for small-to-medium sized labs conducting Sanger sequencing and microsatellite genotyping to store and efficiently handle a relative large amount of data. MolabIS not only helps to avoid time consuming tasks but also ensures the availability of data for further analyses. The software is packaged as a virtual appliance which can run on different platforms (e.g. Linux, Windows). MolabIS can be distributed to a wide range of molecular genetics labs since it was developed according to a general data model. Released under GPL, MolabIS is freely available at http://www.molabis.org. PMID- 22040323 TI - Functional characterisation of HvCO1, the barley (Hordeum vulgare) flowering time ortholog of CONSTANS. AB - Variation in photoperiod response is a major factor determining plant development and the agronomic performance of crops. The genetic control of photoperiodic flowering has been elucidated in the model plant Arabidopsis, and many of the identified genes are structurally conserved in the grasses. In this study, HvCO1, the closest barley ortholog of the key photoperiod response gene CONSTANS in Arabidopsis, was over-expressed in the spring barley Golden Promise. Over expression of HvCO1 accelerated time to flowering in long- and short-day conditions and caused up-regulation of HvFT1 mRNA under long-day conditions. However, the transgenic plants retained a response to photoperiod, suggesting the presence of photoperiod response factors acting downstream of HvCO1 transcription. Analysis of a population segregating for HvCO1 over-expression and natural genetic variation at Ppd-H1 demonstrated that Ppd-H1 acts downstream of HvCO1 transcription on HvFT1 expression and flowering. Furthermore, variation at Ppd-H1 did not affect diurnal expression of HvCO1 or HvCO2. Over-expression of HvCO1 increased transcription of the spring allele of Vrn-H1 in long- and short day conditions, while genetic variation at Ppd-H1 did not affect Vrn-H1 expression. Over-expression of HvCO1 and natural genetic variation at Ppd-H1 accelerated inflorescence development and stem elongation. Thus, HvCO1 probably induces flowering by activating HvFT1 whilst Ppd-H1 regulates HvFT1 independently of HvCO1 mRNA, and all three genes also appear to have a strong effect in promoting inflorescence development. PMID- 22040324 TI - Full-term extrauterine abdominal pregnancy: a case report. AB - INTRODUCTION: Extrauterine abdominal pregnancy is extremely rare and is frequently missed during antenatal care. This is a report of a full-term extrauterine abdominal pregnancy in a primigravida who likely had a ruptured ectopic pregnancy with secondary implantation and subsequently delivered a healthy baby. CASE PRESENTATION: A 23-year-old, Middle Eastern, primigravida presented at 14 weeks gestation with intermittent suprapubic pain and dysuria. An abdominal ultrasound examination showed a single viable fetus with free fluid in her abdomen. A follow-up examination at term showed a breech presentation and the possibility of a bicornute uterus with the fetus present in the left horn of her uterus. Our patient underwent Cesarean delivery under general anesthesia and was found to have a small intact uterus with the fetus lying in her abdomen and surrounded by an amniotic fluid-filled sac. The baby was extracted uneventfully, but the placenta was implanted in the left broad ligament and its removal resulted in massive intraoperative bleeding that necessitated blood and blood products transfusion and the administration of Factor VII to control the bleeding. Both the mother and newborn were discharged home in good condition. CONCLUSIONS: An extrauterine abdominal pregnancy secondary to a ruptured ectopic pregnancy with secondary implantation could be missed during antenatal care and continue to term with good maternal and fetal outcome. An advanced extrauterine pregnancy should not result in the automatic termination of the pregnancy. PMID- 22040325 TI - Children's adjustment in non-traditional families in Israel: the effect of parental sexual orientation and the number of parents on children's development. AB - OBJECTIVES: This study examined differences in children's psychological and social indicators in non-traditional families in Israel, focusing on fatherless families headed by lesbian mothers and single mothers by choice. Although Israel is considered an industrialized westernized country, centrality of the traditional nuclear family predominates this country. METHODS: This factorial design study included four family types: lesbian and heterosexual mothers, each in both single and coupled parenthood. Children's measures included the Child Behavior Checklist, perception of peer relations and perceived self-competence. RESULTS: Children from single parent as opposed to two-parent families exhibited more externalizing behaviour problems and aggressiveness. Children of lesbian mothers reported more prosocial behaviours and less loneliness than children from heterosexual families. No differences emerged for perceived self-competence across family types. CONCLUSION: Mother's sexual orientation did not affect children's adjustment negatively, whereas single parenthood placed children at greater risk for some difficulties. Implications include the need for apprising health professionals of effects of family types on children's development. PMID- 22040327 TI - Development predictive QSAR models for artemisinin analogues by various feature selection methods: a comparative study. AB - Quantitative structure-activity relationship (QSAR) models were derived for 179 analogues of artemisinin, a potent antimalarial agent. The activities of these compounds were investigated by means of multiple linear regression (MLR). To select relevant descriptors, several methods including stepwise selection, successive projection algorithm and an ant colony optimization algorithm (called memorized_ACS) were employed. A wide variety of molecular descriptors belonging to various structural properties were calculated for each molecule. Two matrixes (D1 and D2) of molecular properties were built. The D1 matrix included the calculated descriptors and the D2 matrix contained the first to third orders of the calculated descriptors and the logarithm of absolute values of the calculated descriptors. For both data matrixes, significant QSAR models were obtained by the memorized_ACS algorithm. The reactive and PEOE (partial equalization of orbital electronegativity) descriptors represented the highest impact on the antimalarial activity. The PEOE descriptors belong to partial charge descriptors and the reactive descriptor is an indicator of the presence of the reactive groups in the molecule. The best MLR model has a training error of 0.71 log RA units (r (2 )= 0.81) and a prediction error of 0.48 log RA units (r (2) = 0.88). PMID- 22040326 TI - Quantifying the quality of hand movement in stroke patients through three dimensional curvature. AB - BACKGROUND: To more accurately evaluate rehabilitation outcomes in stroke patients, movement irregularities should be quantified. Previous work in stroke patients has revealed a reduction in the trajectory smoothness and segmentation of continuous movements. Clinically, the Stroke Impairment Assessment Set (SIAS) evaluates the clumsiness of arm movements using an ordinal scale based on the examiner's observations. In this study, we focused on three-dimensional curvature of hand trajectory to quantify movement, and aimed to establish a novel measurement that is independent of movement duration. We compared the proposed measurement with the SIAS score and the jerk measure representing temporal smoothness. METHODS: Sixteen stroke patients with SIAS upper limb proximal motor function (Knee-Mouth test) scores ranging from 2 (incomplete performance) to 4 (mild clumsiness) were recruited. Nine healthy participant with a SIAS score of 5 (normal) also participated. Participants were asked to grasp a plastic glass and repetitively move it from the lap to the mouth and back at a conformable speed for 30 s, during which the hand movement was measured using OPTOTRAK. The position data was numerically differentiated and the three-dimensional curvature was computed. To compare against a previously proposed measure, the mean squared jerk normalized by its minimum value was computed. Age-matched healthy participants were instructed to move the glass at three different movement speeds. RESULTS: There was an inverse relationship between the curvature of the movement trajectory and the patient's SIAS score. The median of the -log of curvature (MedianLC) correlated well with the SIAS score, upper extremity subsection of Fugl-Meyer Assessment, and the jerk measure in the paretic arm. When the healthy participants moved slowly, the increase in the jerk measure was comparable to the paretic movements with a SIAS score of 2 to 4, while the MedianLC was distinguishable from paretic movements. CONCLUSIONS: Measurement based on curvature was able to quantify movement irregularities and matched well with the examiner's observations. The results suggest that the quality of paretic movements is well characterized using spatial smoothness represented by curvature. The smaller computational costs associated with this measurement suggest that this method has potential clinical utility. PMID- 22040328 TI - Why is Kikuchi-Fujimoto disease misleading? AB - BACKGROUND: Kikuchi-Fujimoto disease (KFD) or histiocytic necrotizing lymphadenitis is a rare, benign, autoimmune condition characterized by lymphadenopathy, fever, and neutropenia. KFD has also been frequently reported in association with systemic lupus erythematosus (SLE). REPORT: We report a case of skin manifestations in KFD characterized by malar rash, photosensitivity, panniculitic lesions, positive antinuclear antibodies and nDNA, and negative extractable nuclear antigen. A biopsy performed on deep nodules on the arms revealed an infiltrate of monocytic cells. Electron microscopy showed no lymphocytic infiltrate at or below the basal membrane and no necrotic keratinocytes within the basal cells of the epidermis. CONCLUSION: Histological and ultrastructural data showed that skin manifestations of KFD and SLE share some common features. Electron microscopy analysis can help discriminate between the two diagnoses. PMID- 22040329 TI - Editorial comment on the use of botulinum toxin. PMID- 22040330 TI - Extending ideas about animal welfare assessment to include 'quality of life' and related concepts. AB - Ideas within the animal welfare science arena have evolved continuously throughout the last 30 years, and will continue to do so. This paper outlines some of these developments. These included reformulation of the five freedoms concept into the five domains of potential welfare compromise. This accommodated weaknesses in the former by distinguishing between the physical/functional and the mental factors that contribute to an animal's welfare state. This development reflected a rising scientific acceptance that the mental experiences of animals were legitimate foci for study and highlighted that what the animal itself experiences represents its welfare status. Initially, most concepts of animal welfare emphasised predominantly negative subjective experiences, such as thirst, hunger and pain, and negative affective states or feelings including anxiety, fear and boredom, but today positive experiences or emotions such as satiety, vitality, reward, contentment, curiosity and playfulness are also considered to be important. During the same period, the focus shifted from evaluating the impacts of individual mental subjective experiences or emotions towards seeking a more comprehensive, multifactorial understanding. The five domains concept was specifically designed to achieve this. Subsequent notions about quality of life (QoL) had the same objective, and emphasised the importance of positive experiences. However, some approaches to QoL assessment relied heavily on empathetic speculation about what animals may experience subjectively and this raised concerns about inappropriate anthropomorphic projections. Such pitfalls may be minimised when informed personnel rigorously apply objectively based methodologies to QoL assessments limited to a short time frame. It is clear that both formal and somewhat less formal QoL assessments of this type are already used to guide decision-making about the ongoing care and therapeutic management of animals on a daily basis. However, application of the recently introduced concepts of 'a life not worth living', 'a life worth avoiding', 'a life worth living' and 'a good life' is problematical, because extending the assessment time scale to the whole of life is attended by a number of as yet unresolved difficulties. Accordingly, their value in the practical management of animals is limited so that, at present, reliance on the minimum standards and recommendations for best practice outlined in codes of practice or welfare will continue to be necessary and worthwhile. Nevertheless, these concepts have value in providing a contextual theme that strongly focuses attention on the promotion of a lifelong QoL with an overall balance that is positive. PMID- 22040331 TI - Development and spatial distribution of the free-living stages of Teladorsagia circumcincta and Trichostrongylus colubriformis on pasture: a pilot study. AB - AIMS: To measure the development of Teladorsagia (=Ostertagia) circumcincta and Trichostrongylus colubriformis eggs to third-stage infective larvae (L3) at different times of the year. Also, to measure the spatial distribution of L3 across herbage, soil and faeces, in order to assess whether spatial issues could be important in larval dynamics on pasture. METHODS: Field plots were contaminated with sheep faeces containing approximately 20,000 eggs of each of T. circumcincta and T. colubriformis on five separate occasions, viz 01 December 1996 (summer), 18 March 1998 (autumn), 17 June 1998 (winter), 15 October 1998 (spring), and 23 July 1999 (winter). Replicate plots (n=10) were harvested at intervals for up to 12 months after deposition of faeces, and the number and distribution of L3 were measured. Larvae were sampled from faeces (where these remained), herbage, and three soil zones to a depth of 145 mm. RESULTS: There were large differences between contamination dates in the percentage of eggs that developed to L3. For both species the highest percentage development was for eggs deposited in December (7.8% and 25.9% for T. circumcincta and T. colubriformis, respectively) and the lowest for June (0.4% and 0.03% T. circumcincta and T. colubriformis, respectively). Development in winter was often delayed, and this was always associated with a low yield of larvae, probably due to compounding mortalities associated with long periods of exposure to low temperatures. The relative distribution of L3 present on herbage, in faeces or in the soil varied between sampling times. However, overall the most L3 were recovered from soil (74% and 66% for T.circumcincta and T. colubriformis, respectively, averaged over all samples), and the lowest recoveries were from the herbage. CONCLUSIONS: Although the data are limited, the results indicated that the highest percentage of eggs developed to infective larvae in summer and only minimal development occurred in winter. The data do not support the view that substantial contamination of pastures with sheep parasites occurs over winter. Large numbers of larvae were recovered from soil, which indicates that, assuming they can subsequently migrate onto herbage, soil is a potentially important reservoir of infective larvae in New Zealand. Therefore, the spatial distribution of L3 on pasture may affect both the dynamics and transmission of parasite populations. Further work on both these issues is warranted. PMID- 22040332 TI - Dynamics of the free-living stages of sheep intestinal parasites on pasture in the North Island of New Zealand. 1. Patterns of seasonal development. AB - AIM: To describe the seasonal pattern of development of third-stage infective larvae (L3) from eggs of Teladorsagia (=Ostertagia) circumcincta, Trichostrongylus colubriformis and Haemonchus contortus on pasture in the North Island of New Zealand. METHODS: Sheep faeces containing known numbers of eggs of all three nematode species were deposited on, or buried in, pasture plots at three sites, viz coastal Manawatu, Upper Hutt Valley, and East Cape hill country. Development was measured by recovering L3 from faeces, herbage and soil 28-31 days after deposition on 13-18 occasions, between January 2005 and July 2006. Analysis of the number of larvae recovered used a mixed model including number of eggs deposited, weight of faeces recovered (an assumed indicator of earthworm activity), site, contamination date, and position of deposited faeces, i.e. on the surface or buried. RESULTS: There was a significant effect of contamination date on development of all three species, with maximum numbers of L3 developing between late spring (November) and early autumn (March), and minimum numbers in June and July. There were large differences between species, with H. contortus exhibiting a long period (April to October) where development was close to zero, whereas T. circumcincta developed to some extent all year round. Development of T. colubriformis was intermediate between the other two species. Burying faeces containing nematode eggs increased the number of L3 recovered compared with surface deposition (p <= 0.001), although there were a small number of exceptions involving only T. colubriformis. The weight of faeces recovered at harvest, which was assumed to be an indication of earthworm activity, was correlated with the number of L3 recovered for all species (p<0.001). In a separate analysis, earthworms were assumed to have been active if <5 g faeces remained at harvest. Where this occurred, the number of L3 of T. colubriformis and T.circumcincta recovered was reduced by 56% and 58%, respectively (p<0.001). CONCLUSIONS: A marked seasonal pattern of development was observed for all three species, with the most larvae developing in spring-early autumn and the least in winter. This seasonal pattern was most pronounced in H. contortus and least obvious in T. circumcincta. Burying faeces containing eggs generally resulted in more L3 being recovered, whilst the apparent activity of earthworms resulted in fewer larvae being recovered. PMID- 22040333 TI - Dynamics of the free-living stages of sheep intestinal parasites on pasture in the North Island of New Zealand. 2. Weather variables associated with development. AB - AIM: To identify weather variables associated with the development of eggs of Teladorsagia (=Ostertagia) circumcincta, Trichostrongylus colubriformis and Haemonchus contortus to third-stage infective larvae (L3) under a range of climatic conditions on pasture in the North Island of New Zealand. METHODS: Sheep faeces containing known numbers of eggs of all three nematode species were deposited on, or buried in, pasture plots at three sites, viz coastal Manawatu, Upper Hutt Valley, and East Cape hill country. Development was measured by recovering L3 from faeces, herbage and soil 28-31 days after deposition, on 13-18 occasions between January 2005 until July 2006. Weather data were recorded at each site, and the association between weather variables and number of L3 recovered was analysed using subsets regression to select best-fitting models from several candidate variables, after adjustment for efficiency of recovery of L3. A multiple linear regression model was then developed for each species, to select weather variables that had both significant and substantive effects on the number of L3 recovered. RESULTS: For all species, mean daily temperature was the best predictor of the number of L3 recovered (p=0.001). For T.circumcincta the final model included mean daily temperature and soil temperature (R2=51%), and for T. colubriformis the model only included mean daily temperature (R2=55%). For development of H. contortus, mean daily temperature was the most significant variable, but moisture in the form of rainfall entropy, i.e. the temporal distribution of rainfall, over the first 14 days was also significant in the final model (R2=34%). CONCLUSIONS: Temperature was the most important determinant of developmental success of free-living nematodes on pasture at the study sites, and probably also for other parts of New Zealand with similar climates. Moisture was not significant in the development of T. circumcincta or T.colubriformis, implying that under the generally moist temperate climate in New Zealand, moisture is seldom limiting for development of these species. Haemonchus contortus appeared to be sensitive to moisture availability and precipitation in the first 14 days after deposition of faeces. The results of this study will be further developed as part of species-specific climate-driven models of parasite development in New Zealand. PMID- 22040334 TI - Mycobacterium avium subsp. paratuberculosis infection in wildlife on three deer farms with a history of Johne's disease. AB - AIM: To determine the prevalence of Mycobacterium avium subsp. paratuberculosis (Map) infection in wildlife, in pastoral landscapes with a recent history of clinical Johne's disease in livestock. METHODS: A total of 449 wild mammals and birds from three farms in the South Island of New Zealand with recent histories of clinical Johne's disease in their deer herds were trapped and examined for gross pathological changes in the gastrointestinal tract. Additionally, individual mesenteric lymph nodes from 380 mammals, and segments of gastrointestinal tract from 32 birds were excised, homogenised and cultured for viable Map bacilli. The prevalence of Map infection was then calculated for the various species. Faecal samples from those mammals which had culture-positive tissues were further cultured for the presence of Map. RESULTS: Gross pathological changes were identified in the gastrointestinal tract of four brushtail possums, one cat, six ferrets, 12 hares, six hedgehogs, three rabbits, one stoat, and one paradise shelduck. Infection with Map in the gastrointestinal tract was confirmed in only three of these cases, one each of brushtail possums, hares and hedgehogs. In contrast, Map infection in the absence of gross pathological changes was frequently recorded in enteric tract tissues of mammals and birds. Among mammals, Map infection was recorded in 18/73 (25%) brushtail possums, 4/23 (17%) cats, 15/42 (36%) hedgehogs and 29/113 (26%) rabbits. Among birds, intestinal tract tissue Map infection was recorded in 3/17 (18%) paradise shelducks. Among 64 of the 74 mammals which had Map culture-positive tissues, 38% (n=5) of hedgehogs and 11% (n=3) of rabbits also had culture-positive faecal samples. CONCLUSIONS: This study is the first to identify that Map infection can be prevalent in wildlife in New Zealand. There was a high prevalence of Map infection among both scavenging and grazing wild animals. Both mammals and birds are capable of harbouring viable Map organisms in their gastrointestinal tract; further, viable Map was excreted into the environment via faeces by hedgehogs and rabbits. CLINICAL RELEVANCE: Previous studies overseas have postulated a role of wildlife as reservoirs of Map infection and possible vectors of Johne's disease to livestock. Here, brushtail possums, hedgehogs and rabbits and in particular were identified as potential wildlife hosts for Map infection in New Zealand. This suggests that several wildlife species could contribute to the persistence of Map infection within a wildlife/livestock complex, and potentially, perhaps more importantly, to the spread of infection between farms. PMID- 22040335 TI - Relationship between estimated breeding value for somatic cell count and prevalence of intramammary infection in dairy goats. AB - Abstract AIM: The objective of the study was to determine if dairy goats selected as having either Low or High estimated breeding values for somatic cell count (EBV SCC) would differ in prevalence of intramammary infection (IMI). METHODS: The EBV SCC for all does in two dairy goat herds were calculated based on the three or four herd test results for somatic cell count (SCC) from the preceding lactations. Within each herd does were categorised into six age groups (i.e. 2, 3, 4, 5, 6 and >6 years old) and ranked on EBV SCC. Approximately the top (High group; n=149) and bottom (Low group; n=148) 12.5% of the does within each age group within each herd had milk samples collected from each gland on one calendar day for subsequent microbiology. The presence of any IMI or IMI due to a major pathogen at goat level was modelled using a GLM with a binomial link function. RESULTS: There was no difference between the High and Low groups in terms of age, days in milk at the time of sampling or in the proportion of the Saanen breed. Mean EBV SCC was -1.0 (SD 0.4) vs 0.8 (SD 0.4) for the Low and High groups, respectively, and there was no overlap in EBV SCC between groups. Goats in the Low group had lower prevalence of any IMI than those in the High group (0.67 (95% CI=0.58-0.76) vs 0.81 (95% CI=0.74-0.88); p=0.002). Goats in the High group were 8.4 (95% CI=1.9-38.0) times more likely to have IMI due to a major pathogen infection than goats in the Low group (p=0.006). CONCLUSIONS: Does with a high EBV SCC had a higher prevalence of any IMI and were more likely to have an IMI due to a major pathogen than does with a low EBV SCC. Thus selection for EBV SCC is likely to result in a lower SCC and also lower prevalence of IMI. PMID- 22040336 TI - Attitudes towards perception and management of pain in rabbits and guinea pigs by a sample of veterinarians in New Zealand. AB - AIMS: To determine the perceptions of a sample of veterinarians in New Zealand regarding pain and pain management in rabbits and guinea pigs. METHODS: Questionnaires were distributed to all members of the Companion Animal Society, part of the New Zealand Veterinary Association. The questionnaire gathered information on the demographics of respondents, obtained an assessment by veterinarians of the level of pain associated with clinical procedures for rabbits and guinea pigs, established the willingness of respondents to perform these, obtained information on the anaesthetics and analgesics used during these procedures, and the factors associated with selecting different types of drug. The level of knowledge of respondents and interest in continuing education regarding pain recognition and management in these species was also assessed. RESULTS: A total of 155/610 (25.4%) responses were obtained. Rodents and lagomorphs accounted for 0-5% of the total caseload in the practices of most (133/155; 86%) respondents. Anticipated pain scores differed for different procedures (p<0.001) but did not differ between male and female respondents or between species of animal. There were also differences between procedures in the respondents willingness to perform them (p<0.001). Selection of anaesthetics and analgesics was mainly determined by the amount of information available for the species, and ketamine was the drug most commonly used. Many veterinarians felt their level of knowledge regarding the recognition and treatment of pain in rabbits and guinea pigs was inadequate. CONCLUSIONS: Rabbits and guinea pigs represented a small percentage of the caseload of veterinarians in this study. From an animal welfare perspective this may be of concern as, anecdotally, these species are common pets. However, further study regarding the actual number of these animals kept as pets in New Zealand is required for validation. Veterinary perception of anticipated pain, and willingness to perform procedures, varied between procedures, but was not influenced by gender of veterinarian. Many respondents felt their knowledge of issues relating to pain recognition, anaesthesia and analgesia in rabbits and guinea pigs was inadequate. CLINICAL RELEVANCE: Understanding how veterinarians choose to provide analgesia or when they decline to perform surgeries for rabbits and guinea pigs may provide significant information for targeting professional development, and improving animal welfare. PMID- 22040337 TI - The effects of farming system and season on the prevalence of lameness in sheep in northwest Iran. AB - AIMS: To determine the prevalence of lameness in sheep in Urmia, northwest Iran, and compare the effects of production system and season on prevalence. METHODS: A cross-sectional study, using cluster sampling, was conducted. The selected flocks included 18 with 2,315 sheep from farmed production and 28 with 7,619 sheep from semi-migratory systems, and were visited once in summer (grazing season) and once in winter (housing season). Sheep showing signs of lameness were examined to detect the causes of lameness. Bacteriology and histopathology were also performed if required. RESULTS: The probability of overall lameness was not affected by farming system (p = 0.40), but in the grazing season was less (OR = 0.62; 95% CI = 0.56-0.69) than in the housing season. Footrot was most the common cause of lameness, occurring in 1,047/1,880 (56%) cases. Among flocks, 40/46 (87%) had >= 1 case of footrot. Farming system had no effect on occurrence of footrot (p = 0.85), but the probability of footrot in the grazing season was less (OR = 0.21; 95% CI = 0.18-0.25) than in the housing season. Semi-migratory flocks had less hoof overgrowth (OR = 0.30; 95% CI = 0.16-0.56) than farmed flocks, and the probability of hoof overgrowth in the grazing season was less (OR = 0.19; 95% CI = 0.12-0.29) than in the housing season. The probability of digital abscess was less in semi-migratory flocks (OR = 0.64; 95% CI = 0.46-0.88) than farmed flocks, and in the grazing season was more (OR = 2.14; 95 CI = 1.61-2.85) than in the housing season. The probability of interdigital gland infection was higher (OR = 7.15; 95% CI = 5.36-9.55) in the grazing season than in the housing season. Staphylococcus aureus was isolated from 9/11 (82%) sheep affected with interdigital gland infection. CONCLUSIONS: Footrot was the main cause of lameness in sheep in both farmed and semi-migratory farming systems in this study, especially in the housing season. In the grazing season, digital abscess and interdigital gland infection should be considered as common causes of sporadic lameness in sheep. CLINICAL RELEVANCE: In practice, lameness in sheep can be a major concern both in farmed and semi-migratory farming systems, with a high occurrence in the housing season. Footrot was a main cause of lameness in sheep in northwest Iran. PMID- 22040338 TI - Culture results from milk samples submitted to veterinary diagnostic laboratories from August 2003 to December 2006 in New Zealand. AB - AIMS: To determine the pattern of isolation of major mastitis-causing organisms isolated from milk samples submitted to five veterinary diagnostic laboratories in New Zealand. METHODS: The culture results of 25,288 milk samples that were collected from dairy cows throughout New Zealand from August 2003 to December 2006 and submitted to a group of veterinary diagnostic laboratories were assembled, reviewed and summarised. Logistic regression was used to analyse the effect of year, region (i.e. North vs South Island), and season on the probability of isolating the two most common organisms. RESULTS: The most commonly isolated mastitis causing organisms from all samples were: Streptococcus uberis (23.6%), Staphylococcus aureus (23.5%), coagulase-negative staphylococci (CNS; 7.2%), Strep. dysgalactiae (6.2%), Bacillus spp. (4.0%), and coliforms (3.7%). The percentage of samples with isolates of Strep. uberis or Staph. aureus was affected by island, year and season (p<0.001). For most of the year, except in late winter and early spring when Strep. uberis was much more common, the percentage of isolates of Strep. uberis and Staph. aureus were not apparently different despite the former being an environmental pathogen and the other a contagious one. CONCLUSION: The pattern of isolation of major mastitis-causing organisms, as determined from culture of milk samples submitted to diagnostic laboratories in New Zealand, has changed significantly over the last 40 years, with a substantial increase in the percentage of isolates that are Strep. uberis and a decrease in isolates of Strep. agalactiae. There is a clear seasonal pattern to the isolation of both Strep. uberis and Staph. aureus, particularly the former. CLINICAL RELEVANCE: Knowledge of the aetiological agents causing bovine mastitis on a farm is of value in determining the choice of treatment. This dataset shows that, although there is seasonal pattern to the isolation of mastitis-causing organisms in New Zealand, both Strep. uberis and Staph. aureus are isolated throughout the year, so bacteriology is of value in determining aetiology even in late winter/early spring. PMID- 22040339 TI - The relationship of training milestones with racing success in a population of Standardbred horses in New Zealand. AB - AIM: To investigate the association between attainment of training milestones by 2-year-old horses with racing outcomes in a population of Standardbred racehorses in New Zealand. METHODS: Retrospective records of the 2001/2002-born Standardbred foals were obtained. The three training milestones used were: registered with a trainer, entered in a trial, and competed in a race. The racing outcomes were length of career in years raced and number of race starts, and total earnings. Cox regression analysis was used to assess the association between attainment of the three milestones by 2-year-olds and the number of race starts and years raced. Logistic regression models were used to determine the association between attainment of the milestones by 2-year-olds and the outcomes won and placed in a race. Linear regression was used to model the association between attainment of the milestones by 2-year-olds and annual earnings and total earnings (transformed using Ln (earnings+NZ$100)). RESULTS: Of 3,032 horses in the population, 1,018 (33.6%) registered with a trainer, 609 (20.1%) trialled, and 272 (9.0%) raced as 2-year-olds. Horses that first raced as 2-year-olds had a longer racing career and more race starts than those that that did not race as 2-year-olds (p<0.001); this was also true when starts in the 2-year-olds were omitted from analyses. Horses that were registered with a trainer, trialled or raced as 2-year-olds were more likely to have won or placed in a race than those that did not achieve the milestones as 2-year-olds (p<0.001). Linear regression showed horses that trialled and raced as 2-year-olds had greater total earnings than those that did not, and male horses had a greater total earnings than female horses. CONCLUSION: Only one third the Standardbred racehorses born in 2001/2002 registered with a trainer as 2-year-olds, but the results of this study indicate that horses that began training, trialling, or racing as 2-year-olds had longer and more successful careers than those that did not achieve the milestones as 2-year-olds. Further investigation is required to quantify the management practices of these horses to determine the factors that may be associated with a successful racing career. PMID- 22040340 TI - Efficacy of tropicamide, homatropine, cyclopentolate, atropine and hyoscine as mydriatics in Angora goats. AB - AIM: To document the efficacy of five commercially available mydriatics for their potential for diagnostic and therapeutic use in Angora goats. METHODS: Over 8 weeks, the mydriatic effects of 1% tropicamide, 2% homatropine, 1% cyclopentolate, 1% atropine and 0.25% hyoscine were evaluated. Given as block treatments, drugs were applied randomly to one eye of 10 Angora goats, and the contralateral eye served as a control. Vertical and horizontal pupil diameters were measured to document onset of effect, time to reach a difference of 5 mm in the vertical/horizontal pupil diameter between eyes, time to maximum pupillary dilation, and duration of mydriatic action. RESULTS: Onset of mydriasis for all drugs occurred within 15 minutes. Time to reach a difference of 5 mm in the vertical pupil diameter between eyes was shortest for 1% tropicamide and 0.25% hyoscine (0.5 h), then 2% homatropine and 1% atropine (0.75 h), and longest for 1% cyclopentolate (1.5 h). The maximum vertical pupillary dilation occurred earliest with 1% tropicamide and 1% atropine (2 h), followed by 0.25% hyoscine (3 h), 2% homatropine (4 h), and latest with 1% cyclopentolate (8 h). The duration of vertical dilation of the pupil was shortest with 1% tropicamide (6 h), then 2% homatropine (12 h), 1% cyclopentolate (12 h), 1% atropine (24 h), and longest for 0.25% hyoscine (96 h). The time to reach maximum horizontal dilation of the pupil in treated eyes was shortest with 1% cyclopentolate (1 h), followed by 1% tropicamide (1.5 h), 0.25% hyoscine (3 h), 2% homatropine (3.5 h), and 1% atropine (4 h). The duration of horizontal pupil dilation was shortest with 1% tropicamide (4.5 h), and longest with 0.25% hyoscine (48 h). CONCLUSION: All five mydriatics induced clinical dilation. Tropicamide (1%) had the shortest duration of effect, but gave incomplete dilation. Good dilation was achieved with 1% cyclopentolate and 2% homatropine, but took too long to reach maximum dilation for routine mydriasis. The largest vertical dilation of the pupil was achieved with 1% atropine and 0.25% hyoscine, but pupils remained dilated for more than 24 h. CLINICAL RELEVANCE: For routine mydriasis in goats, it is recommended that 1% tropicamide be used, though there may be incomplete dilation. For a longer duration of mydriasis, such as in the treatment of anterior uveitis, 1% atropine or 0.25% hyoscine would be the drugs of choice. PMID- 22040341 TI - Haemangiosarcoma of the interventricular septum in a dog. AB - Abstract CASE HISTORY: A 5-year-old male neutered Labrador Retriever Afghan crossbred dog was examined after collapsing. The dog was recumbent, dyspnoeic and mildly tachypnoeic. There was a tachyarrhythmia (300 beats per minute) and subcutaneous oedema of the ventral neck and right forelimb. CLINICAL FINDINGS: The dog had a sustained ventricular tachycardia originating in the right ventricle and on echocardiography a mass was identified in the interventricular septum. Due to the poor prognosis the owners agreed to euthanasia of the dog. PATHOLOGICAL FINDINGS: A reddish-grey mass was found in the interventricular septum and smaller red foci found scattered throughout the myocardium. There was a single, raised, splenic nodule with several smaller red foci within the splenic parenchyma. Hepatic congestion, pancreatic oedema, ascites and subcutaneous oedema of the right forelimb and neck were present. Sections of the splenic nodule, interventricular septal mass and both ventricular-free walls showed neoplastic mesenchymal cells. DIAGNOSIS: Haemangiosarcoma of the myocardium and spleen with right-sided congestive heart failure. CLINICAL RELEVANCE: This case report describes an atypical location for haemangiosarcoma. The investigation supports the use of echocardiography as a component of the protocol for staging haemangiosarcoma even in the absence of apericardial effusion. It also provides further evidence for the inclusion of intracardiac neoplasia as a differential diagnosis for dogs with unexplained cardiac arrhythmias. PMID- 22040346 TI - Significance of CO2 donor on the production of succinic acid by Actinobacillus succinogenes ATCC 55618. AB - BACKGROUND: Succinic acid is a building-block chemical which could be used as the precursor of many industrial products. The dissolved CO2 concentration in the fermentation broth could strongly regulate the metabolic flux of carbon and the activity of phosphoenolpyruvate (PEP) carboxykinase, which are the important committed steps for the biosynthesis of succinic acid by Actinobacillus succinogenes. Previous reports showed that succinic acid production could be promoted by regulating the supply of CO2 donor in the fermentation broth. Therefore, the effects of dissolved CO2 concentration and MgCO3 on the fermentation process should be investigated. In this article, we studied the impacts of gaseous CO2 partial pressure, dissolved CO2 concentration, and the addition amount of MgCO3 on succinic acid production by Actinobacillus succinogenes ATCC 55618. We also demonstrated that gaseous CO2 could be removed when MgCO3 was fully supplied. RESULTS: An effective CO2 quantitative mathematical model was developed to calculate the dissolved CO2 concentration in the fermentation broth. The highest succinic acid production of 61.92 g/L was obtained at 159.22 mM dissolved CO2 concentration, which was supplied by 40 g/L MgCO3 at the CO2 partial pressure of 101.33 kPa. When MgCO3 was used as the only CO2 donor, a maximal succinic acid production of 56.1 g/L was obtained, which was just decreased by 7.03% compared with that obtained under the supply of gaseous CO2 and MgCO3. CONCLUSIONS: Besides the high dissolved CO2 concentration, the excessive addition of MgCO3 was beneficial to promote the succinic acid synthesis. This was the first report investigating the replaceable of gaseous CO2 in the fermentation of succinic acid. The results obtained in this study may be useful for reducing the cost of succinic acid fermentation process. PMID- 22040347 TI - Structural flexibility and role of vicinal 2-thienyl rings in 2,3-dicyano-5,6 di(2-thienyl)-1,4-pyrazine, [(CN)2Th2Pyz], its palladium(II) complex [(CN)2Th2Pyz(PdCl2)2], and the related pentametallic pyrazinoporphyrazines [(PdCl2)4Th8TPyzPzM] (M = Mg(II)(H2O), Zn(II)). AB - The solid state and solution structure of 2,3-dicyano-5,6-di(2-thienyl)-1,4 pyrazine, [(CN)(2)Th(2)Pyz], and its Pd(II) derivative, [(CN)(2)Th(2)Pyz(PdCl(2))(2)].H(2)O, formed by reaction of [(CN)(2)Th(2)Pyz] with [(C(6)H(5)CN)(2)PdCl(2)] were characterized by X-ray, UV-visible, (1)H and (13)C NMR, and extended X-ray absorption fine structure (EXAFS) spectral measurements. The X-ray crystal structure of [(CN)(2)Th(2)Pyz] shows the presence of one thienyl ring positioned orthogonal to the rest of the molecule, with the two vicinal thienyl rings lying orthogonal to each other in a rare arrangement. NMR studies of [(CN)(2)Th(2)Pyz] in the solid state and in solutions of dimethylformamide or dimethyl sulfoxide confirm a nonequivalence of the thienyl rings in the solid state and also in solution. EXAFS results indicate that two distinct Pd(II) coordination sites are formed at the di(2-thienyl)pyrazino moiety of [(CN)(2)Th(2)Pyz(PdCl(2))(2)].H(2)O, with identical Pd-N(pyz) (2.03(3) A) and Pd-Cl (2.36(3) A) bond lengths but with different Pd-S1 (2.25(4) A) and Pd-S2 (3.21(5) A) bond distances in an overall asymmetric molecular framework. Density functional theory (DFT) and time-dependent DFT (TDDFT) theoretical studies also provide information about the structure and spectral behavior of the precursor and its metalated Pd(II) derivative. (1)H/(13)C NMR and UV-visible spectral measurements were also carried out on two heteropentametallic porphyrazine macrocycles which were prepared by a reaction of PdCl(2) with [Th(8)TPyzPzM] where Th(8)TPyzPz = tetrakis-2,3-[5,6-di-(2-thienyl)-pyrazino]porphyrazinato dianion and M = Mg(II)(H(2)O) or Zn(II). Spectroscopic data on the newly synthesized [(PdCl(2))(4)Th(8)TPyzPzM] compounds suggest that the binding of PdCl(2) involves coordination sites of the type S(2(th))PdCl(2) with the two thienyl rings of each di(2-thienyl)pyrazino fragment bound to Pd(II) in an equivalent manner ("th-th" coordination). This is similar to what was found for the corresponding octapyridinated analogues ("py-py" coordination). PMID- 22040348 TI - Policy implications for familial searching. AB - In the United States, several states have made policy decisions regarding whether and how to use familial searching of the Combined DNA Index System (CODIS) database in criminal investigations. Familial searching pushes DNA typing beyond merely identifying individuals to detecting genetic relatedness, an application previously reserved for missing persons identifications and custody battles. The intentional search of CODIS for partial matches to an item of evidence offers law enforcement agencies a powerful tool for developing investigative leads, apprehending criminals, revitalizing cold cases and exonerating wrongfully convicted individuals. As familial searching involves a range of logistical, social, ethical and legal considerations, states are now grappling with policy options for implementing familial searching to balance crime fighting with its potential impact on society. When developing policies for familial searching, legislators should take into account the impact of familial searching on select populations and the need to minimize personal intrusion on relatives of individuals in the DNA database. This review describes the approaches used to narrow a suspect pool from a partial match search of CODIS and summarizes the economic, ethical, logistical and political challenges of implementing familial searching. We examine particular US state policies and the policy options adopted to address these issues. The aim of this review is to provide objective background information on the controversial approach of familial searching to inform policy decisions in this area. Herein we highlight key policy options and recommendations regarding effective utilization of familial searching that minimize harm to and afford maximum protection of US citizens. PMID- 22040349 TI - Infection after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use. AB - Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Septicaemia is the most frequent cause of hospitalization after transtrectal prostate biopsy; fatalities have been reported and the incidence is on the rise. This study shows that men with a history of recent international travel or antibiotic use have up to four times increased risk of septicaemia and hospitalization. When they do occur, infections are usually due to multi-resistant E coli and additional care, e.g. delay before biopsy, different antibiotic prophylaxis or transperineal biopsy, should be considered in these cases. OBJECTIVE * To study the infection rate after prostate biopsy in those who have travelled overseas or used antibiotics in the 4 weeks before biopsy. PATIENTS AND METHODS * A total of 316 men with a mean (range) age of 61 (45-85) years were studied. All had undergone transrectal ultrasonography (TRUS)-guided prostate biopsy after standard antibiotic prophylaxis. * Before their biopsy the patients were risk stratified and a history of recent international travel or antibiotic use was recorded. * Those who suffered sufficiently severe infection/sepsis so as to require hospitalization were identified at the end of the study period. * The characteristics of these patients and the types of infections were explored and the relative risk (RR) of infection after recent travel or antibiotic use was calculated. RESULTS * Of the 316 men, 16 were hospitalized with infection. * The group with (n= 16) and without (n= 300) infection were equivalent in age, prostate-specific antigen level, disease status and number of biopsy cores taken. * Either recent travel or antibiotic use were independent risk factors for infection [travel: 8/16 vs 76/300; P= 0.04; RR 2.7 and antibiotic use: 4/16 vs 20/300; P= 0.025; RR 4]. There was no significant pattern in the countries visited or the type of antibiotic used. * Culture results were positive in 10/16 men, and all cultures grew multiresistant Escherichia coli. The strains were uniformly resistant to ciprofloxacin and amoxycillin, and variably resistant to gentamicin and co amoxiclav, but nearly all were sensitive to meropenem. * All patients made a full recovery after antibiotic and supportive treatment. CONCLUSIONS * Either recent international travel or antibiotic use are independent risk factors for severe infection after TRUS-guided prostate biopsy. * When infection does occur it should be treated aggressively as the causative agent is usually a multiresistant E. coli. PMID- 22040350 TI - Patients with univentricular heart in early childhood: parenting stress and child behaviour. AB - AIMS: To assess perceptions of child behaviour and parenting stress among the parents of young children with hypoplastic left heart syndrome (HLHS) and other forms of functionally univentricular heart defects (UVH). METHODS: As part of our prospective nation-wide neurodevelopmental follow-up study, the parents of 23 patients with HLHS, 14 with UVH and 46 healthy controls at the mean age of 18 months received the questionnaires Child Behavior Checklist and Parenting Stress Index. RESULTS: The reported level of total parenting stress was significantly higher among the mothers (mean score 241 vs 205, p < 0.001) and fathers (235 vs 202, p = 0.003) of patients with HLHS compared with those of controls. The parents of patients with HLHS reported significantly more total (mean T score 52 vs 45, p = 0.005) and internalizing (51 vs 41, p < 0.001) behaviour problems than the controls, but among the syndrome scales, a significant difference was only found in somatic complaints. The parents of patients with UVH did not report more parenting stress or emotional problems than the controls. CONCLUSION: Hypoplastic left heart syndrome, a severe congenital heart defect, increases parenting stress. The reported emotional maladjustment in affected children might in part be owing to somatic complaints. PMID- 22040351 TI - Variable agronomic practices, cultivar, strain source and initial contamination dose differentially affect survival of Escherichia coli on spinach. AB - AIMS: Greenhouse and field trials were conducted under different agronomic practices and inoculum doses of environmental Escherichia coli and attenuated E. coli O157:H7, to comparatively determine whether these factors influence their survival on leaves and within the rhizosphere. METHODS AND RESULTS: Hydroponic conditions: E. coli spray-inoculated at log 4 CFU ml(-1) was recovered from leaf surfaces at a mean population of 1.6 log CFU g(-1) at 15 days. E. coli O157:H7 sprayed at log 2 or 4 CFU ml(-1) levelled off on spinach leaf surfaces at a mean average population of 1.4 log CFU g(-1) after 14 days, regardless of initial dose. Quantitative recovery was inconsistent across leaf developmental age. Field conditions: Average populations of E. coli O157:H7 spray-inoculated at log 1.45 or 3.4 CFU m(-2) levelled off at log 1.2 CFU g(-1) over a 14-day period. Pathogen recovery from leaves was inconsistent when compared to regularly positive detection on basal shoot tissue. Pathogen recovery from soil was inconsistent among sampling locations. Moisture content varied up to 40% DW and was associated with 50% (P < 0.05) decrease in positive locations for E. coli O157:H7 but not for E. coli. CONCLUSIONS: Overall, similar populations of environmental E. coli and E. coli O157:H7 were recovered from plants despite differences in inoculum dose and agronomic conditions. Strain source had a significant impact on the quantitative level and duration of survival on leaves and in soil. Water availability appeared to be the determinant factor in survival of E. coli and E. coli O157:H7; however, E. coli showed greater environmental fitness. SIGNIFICANCE AND IMPACT OF THE STUDY: Persistence of surrogate, indicator E. coli and E. coli O157:H7, irrespective of variable growing conditions in spinach is predominantly limited by water availability, strain source and localization within the plant. These findings are anticipated to ultimately be adopted into routine and investigative pathogen testing protocols and mechanical harvest practices of spinach. PMID- 22040352 TI - Dancing on coke: smuggling cocaine dispersed in polyvinyl alcohol. AB - Recent trends suggest that cocaine smugglers have become more and more inventive to avoid seizures of large amounts of cocaine transported between countries. We report a case of a mail parcel containing a dance pad which was seized at the Customs Department of Brussels Airport, Belgium. After investigation, the inside of the dance pad was found to contain a thick polymer, which tested positive for cocaine. Analysis was performed using a routine colorimetric swipe test, gas chromatography coupled with mass spectrometry and nuclear magnetic resonance spectroscopy. The polymer was identified as polyvinyl alcohol (PVA) and contained 18% cocaine, corresponding to a street value of ? 20,000. Laboratory experiments showed that cocaine could be easily extracted from the PVA matrix. This case report reveals a new smuggling technique for the transportation of large amounts of cocaine from one country to another. PMID- 22040353 TI - Why do even satisfied newlyweds eventually go on to divorce? AB - Although divorce typically follows an extended period of unhappiness that begins early in marriage, some couples who are very happy throughout the first several years of marriage will also go on to divorce. This study aimed to identify risk factors early in marriage that distinguish initially satisfied couples who eventually divorce from those who remain married. We identified 136 couples reporting stably high levels of relationship satisfaction in the first 4 years of marriage. We compared the couples who went on to divorce by the 10-year follow-up with the couples who remained married on initial measures of commitment, observed communication, stress, and personality. Divorcing couples displayed more negative communication, emotion, and social support as newlyweds compared with couples who did not divorce. No significant differences were found in the other domains, in relationship satisfaction, or in positive behaviors. Overall, results indicate that even couples who are very successful at navigating the early years of marriage can be vulnerable to later dissolution if their interpersonal exchanges are poorly regulated. We speculate that, paradoxically, the many strengths possessed by these couples may mask their potent interpersonal liabilities, posing challenges for educational interventions designed to help these couples. PMID- 22040354 TI - Disinfection of bacterially contaminated hydrophilic PVS impression materials. AB - PURPOSE: This study evaluated disinfection of bacterially contaminated hydrophilic polyvinylsiloxane (PVS) and polyether impressions. MATERIALS AND METHODS: Four light-bodied PVS (Examix, Genie, Take 1, Aquasil) and one polyether (Impregum) impression materials were evaluated using three disinfectants (EcoTru [EnviroSystems], ProSpray [Certol], and bleach [diluted 1:9]) as spray and immersion disinfections for 10-minute exposures. Pseudomonas aeruginosa ATCC 15442, Salmonella choleraesius ATCC 10708, and Staphylococcus aureus ATCC 6538 was the microbial challenge. Test specimens were prepared using aluminum molds with ten tapered cones. Mucin covered each cone, followed by 0.01 mL of each bacterium. Impressions were made using low viscosity impression material that was injected over the cones and filled custom trays. One-half of the impressions were spray disinfected, while the others underwent immersion disinfection. Trays that were contaminated but not disinfected served as positive controls, while those not bacterially contaminated or disinfected served as negative controls. The impressions were poured with Silky Rock Die Stone, and after setting, two cones were placed within a sterile capsule and triturated into powder. Four milliliters of TRIS buffer (0.05 M, pH 7.0) containing sodium thiosulfate (0.0055% w/v) were poured in each tube. After mixing, the solution was serially diluted and spread plated onto selective agars. After incubation, colony counting occurred. RESULTS: No viable bacteria transferred to casts from either spray- or immersion disinfected impressions. Negative controls produced no microbial colonies. Positive controls produced on average 3.35 * 10(5) bacterial cells. CONCLUSION: Results suggest the methods used could disinfect contaminated impression materials. Microbial transfer from nondisinfected impressions to cones approached 33.5%. PMID- 22040355 TI - Synthesis of well-ordered COF monolayers: surface growth of nanocrystalline precursors versus direct on-surface polycondensation. AB - Two different straightforward synthetic approaches are presented to fabricate long-range-ordered monolayers of a covalent organic framework (COF) on an inert, catalytically inactive graphite surface. Boronic acid condensation (dehydration) is employed as the polymerization reaction. In the first approach, the monomer is prepolymerized by a mere thermal treatment into nanocrystalline precursor COFs. The precursors are then deposited by drop-casting onto a graphite substrate and characterized by scanning tunneling microscopy (STM). While in the precursors monomers are already covalently interlinked into the final COF structure, the resulting domain size is still rather small. We show that a thermal treatment under reversible reaction conditions facilitates on-surface ripening associated with a striking increase of the domain size. Although this first approach allows studying different stages of the polymerization, the direct polymerization, that is, without the necessity of preceding reaction steps, is desirable. We demonstrate that even for a comparatively small diboronic acid monomer a direct thermally activated polymerization into extended COF monolayers is achievable. PMID- 22040356 TI - Validation of an axial flow blood pump: computational fluid dynamics results using particle image velocimetry. AB - A magnetically suspended axial flow blood pump is studied experimentally in this article. The pump casing enclosed a three-blade straightener, a two-blade impeller shrouded by a permanent magnet-embedded cylinder, and a three-blade diffuser. The internal flow fields were simulated earlier using computational fluid dynamics (CFD), and the pump characteristic curves were determined. The simulation results showed that the internal flow field was basically streamlined, except the diffuser region. Particle image velocimetry (PIV) measurement of the 1:1 pump model was conducted to validate the CFD result. In order to ensure the optical access, an acrylic prototype was fabricated with the impeller driven by a servomotor instead, as the magnet is opaque. In addition to the transparent model, the blood analog fluid with the refractive index close to that of acrylic was used to avoid refraction. According to the CFD results, the axial flow blood pump could generate adequate pressure head at the rotating speed of 9500rpm and flow rate of 5L/min, and the same flow condition was applied during the PIV measurement. Through the comparisons, it was found that the experimental results were close to those obtained by CFD and had thus validated the CFD model, which could complement the limitation of the measurement in assessing the more detailed flow fields of the axial flow pump. PMID- 22040357 TI - Inhibition of highly pathogenic PRRSV replication in MARC-145 cells by artificial microRNAs. AB - BACKGROUND: Highly pathogenic porcine reproductive and respiratory syndrome (HP PRRS) has caused large economic losses in swine industry in recent years. However, current antiviral strategy could not effectively prevent and control this disease. In this research, five artificial microRNAs (amiRNAs) respectively targeted towards ORF5 (amirGP5-243, -370) and ORF6 (amirM-82, -217,-263) were designed and incorporated into a miRNA-based vector that mimics the backbone of murine miR-155 and permits high expression of amiRNAs in a GFP fused form mediated by RNA Pol II promoter CMV. RESULTS: It was found that amirGP5-370 could effectively inhibit H-PRRSV replication. The amirM-263-M-263, which was a dual pre-amiRNA expression cassette where two amirM-263s were chained, showed stronger virus inhibitory effects than single amirM-263. H-PRRSV replication was inhibited up to 120 hours in the MARC-145 cells which were stably transduced by recombinant lentiviruses (Lenti-amirGP5-370, -amirM-263-M-263). Additionally, efficacious dose of amirGP5-370 and amirM-263 expression did not trigger the innate interferon response. CONCLUSIONS: Our study is the first attempt to suppress H PRRSV replication in MARC-145 cells through vector-based and lentiviral mediated amiRNAs targeting GP5 or M proteins coding sequences of PRRSV, which indicated that artificial microRNAs and recombinant lentiviruses might be applied to be a new potent anti-PRRSV strategy. PMID- 22040358 TI - Nasopharyngeal cancer mimicking otitic barotrauma in a resource-challenged center: a case report. AB - INTRODUCTION: Nasopharyngeal cancer commonly manifests with cervical lymphadenopathy, recurrent epistaxis and progressive nasal obstruction. Neuro ophthalmic and otologic manifestations can also occur. Isolated otologic presentations of nasopharyngeal cancer are rare and the diagnosis of nasopharyngeal cancer may not be foremost in the list of differentials. CASE PRESENTATION: We present the case of a 29-year-old Nigerian woman with bilateral conductive hearing loss and tinnitus after air travel. There were no other symptoms. The persistence of the symptoms after adequate treatment for otitic barotrauma necessitated re-evaluation, which led to a diagnosis of nasopharyngeal cancer. CONCLUSION: Isolated otologic manifestations of nasopharyngeal cancer are rare in regions with low incidence of the disease. There is a need for it to be considered as a possible differential in patients presenting with bilateral serous otitis media. PMID- 22040360 TI - Growth, clinical chemistry and immune function in domestic piglets fed varying ratios of arachidonic acid and DHA. AB - In the USA, infant formulas contain long-chain PUFA arachidonic acid (ARA) and DHA in a ratio of 2:1 and comprise roughly 0.66 g/100 g and 0.33 g/100 g total fatty acids (FA). Higher levels of dietary DHA appear to provide some advantages in visual or cognitive performance. The present study evaluated the effect of physiologically high dietary ARA on growth, clinical chemistry, haematology and immune function when DHA is 1.0 g/100 g total FA. On day 3 of age, formula-reared (FR) piglets were matched for weight and assigned to one of six milk replacer formulas. Diets varied in the ratio of ARA:DHA as follows (g/100 g FA/FA): A1, 0.1/1.0; A2, 0.53/1.0; A3-D3, 0.69/1.0; A4, 1.1/1.0; D2, 0.67/0.62; D1, 0.66/0.33. A seventh group was maternal-reared (MR) and remained with the dam during the study. Blood collection and body weight measurements were performed weekly, and piglets were killed on day 28 of age. No significant differences were found among any of the FR groups for formula intake, growth, clinical chemistry, haematology or immune status measurements. A few differences in clinical chemistry, haematology and immune function parameters between the MR pigs and the FR groups probably reflected a difference in growth rate. We conclude that the dietary ARA level up to 1.0 g/100 g total FA is safe and has no adverse effect on any of the safety outcomes measured, and confirm that DHA has no adverse effect when ARA is at 0.66 g/100 g FA. PMID- 22040359 TI - Thermal stability of hepatitis E virus assessed by a molecular biological approach. AB - BACKGROUND: Hepatitis E virus (HEV) is a pathogen of emerging concern in industrialized countries. The consumption of wild boar meat has been identified as one risk factor for autochthonous HEV infections. Only limited information is available about thermal stability of HEV, mainly due to the lack of rapid and efficient cell culture systems for measurement of HEV infectivity. METHODS: A molecular biological method was implemented in order to distinguish disassembled from intact viral particles using RNase treatment followed by quantitative real time RT-PCR. The method was applied to a wild boar liver suspension containing HEV genotype 3. RESULTS: Time-course analyses indicated that the decline of protected RNA could be described by a biphasic model with an initial decrease followed by a stationary phase. The stationary phase was reached after 1 hour at 4 degrees C, 3 days at 22 degrees C and 7 days at 37 degrees C with log reductions of 0.34, 0.45 and 1.24, respectively. Protected RNA was detectable until the end of the experiments at day 50 or 70. Heat exposure for 1 minute resulted in a log reduction of 0.48 at 70 degrees C and increased with higher temperatures to 3.67 at 95 degrees C. Although HEV infectivity titration by inoculation of the liver suspension onto three cell lines did not succeed, the results of the RNase-based method are in accordance with published cell culture based data. CONCLUSIONS: Measurement of intact viral particles using the RNase based method may provide data on the stability of RNA viruses when cell culture based infectivity titrations are not efficient or not available. The method enables processing of large sample numbers and may be suitable to estimate stability of HEV in different types of food. PMID- 22040361 TI - Misconceptions about the side effects of combined oral contraceptive pills. AB - OBJECTIVE: Although combined oral contraceptive pills (COCPs) are one of the most commonly used methods of contraception in western countries, they are taken by only a minority of sexually active women in Turkey. The purpose of this research has been to define women's specific misconceptions with regard to the side effects of COCPs. METHODS: This descriptive and cross-sectional research was conducted on 418 reproductive aged women who agreed to participate. Data were collected through face-to-face interviews with a questionnaire which assessed socio-demographic characteristics and women's beliefs about the side effects of COCPs. RESULTS: It is observed that 45.2% believed that the pills cause weight gain. Another 7.9% of the cases held the belief that COCPs cause cancer. A group of 13.4% of the subjects thought that COCPs lead to infertility, 28.7% believed that they cause headache, 41.1% believed that they cause acne and/or an increase in body hair, and 11.7% were afraid that they cause a decrease in libido. CONCLUSION: The present study has shown that misconceptions about the side effects of COCPs were considerably prevalent among this cohort group of Turkish women. Healthcare professionals have the potential of playing an important role in dispersing these misconceptions. PMID- 22040362 TI - Characterization of the Asian myopathy patients with VCP mutations. AB - BACKGROUND AND PURPOSE: Mutations in the valosin-containing protein (VCP) gene are known to cause inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and familial amyotrophic lateral sclerosis (ALS). Despite an increasing number of clinical reports, only one Asian family with IBMPFD has been described. METHODS: To characterize patients with VCP mutations, we screened a total of 152 unrelated Asian families who were suspected to have rimmed vacuolar myopathy. RESULTS: We identified VCP mutations in seven patients from six unrelated Asian families. Five different missense mutations were found, including a novel p.Ala439Pro substitution. All patients had adult onset progressive muscle wasting with variable involvement of axial, proximal, and distal muscles. Two of seven patients were suggested to have mild brain involvement including cerebellar ataxia, and only one showed radiological findings indicating a change in bone. Findings from skeletal muscle indicated mixed neurogenic and myogenic changes, fibers with rimmed vacuoles, and the presence of cytoplasmic and nuclear inclusions. These inclusions were immunopositive for VCP, ubiquitin, transactivation response DNA-binding protein 43, and also histone deacetylase 6 (HDAC6), of which function is regulated by VCP. Evidence of early nuclear and mitochondrial damage was also characteristic. CONCLUSIONS: Valosin-containing protein mutations are not rare in Asian patients, and gene analysis should be considered for patients with adult-onset rimmed vacuolar myopathy with neurogenic changes. A wide variety of central and peripheral nervous system symptoms coupled with rare bone abnormalities may complicate diagnosis. PMID- 22040363 TI - Uncovering genetic and molecular interactions among floral meristem identity genes in Arabidopsis thaliana. AB - The inflorescence meristem produces floral primordia that remain undifferentiated during the first stages of flower development. Genes controlling floral meristem identity include LEAFY (LFY), APETALA1 (AP1), CAULIFLOWER (CAL), LATE MERISTEM IDENTITY 1 (LMI1), SHORT VEGETATIVE PHASE (SVP) and AGAMOUS-LIKE24 (AGL24). The lfy mutant shows partial reversions of flowers into inflorescence shoot-like structures and this phenotype is enhanced in the lfy ap1 double mutant. Here we show that combining the lfy mutant with agl24 and svp single mutants or with the agl24 svp double mutant enhances the lfy phenotype and that the lfy agl24 svp triple mutant phenocopies the lfy ap1 double mutant. Analysis of the molecular interactions between LFY, AGL24 and SVP showed that LFY is a repressor of AGL24 and SVP, whereas LMI1 is a positive regulator of these genes. Moreover, AGL24 and SVP positively regulate AP1 and LFY by direct binding to their regulatory regions. Since all these genes are important for establishing floral meristem identity, regulatory loops are probably important to maintain the correct relative expression levels of these genes. PMID- 22040364 TI - An immunohistochemical study of the origin of the solid strand in syringoma, using carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin 5. AB - BACKGROUND: Although much research has been conducted into the origin of syringoma, the histogenesis and differentiation of it remains controversial. The published studies examined various antibodies, and our study is an additional immunohistochemical work-up. OBJECTIVE: We attempted to identify the cell that acts as the precise origin of a syringoma, based on a comparative analysis of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratin (CK) 5 through immunohistochemical staining in the solid strand of basophilic epithelial cells of syringoma. METHODS: A total of 31 patients with biopsy-confirmed syringoma were included in this study. Each sample was analyzed with antibodies to CEA, EMA, and CK5. These markers were indicating each part of the normal sweat gland structure: CEA stains the luminal surface of sweat ductal structures; EMA stains the peripheral cells of normal dermal ducts and the intraepidermal duct; CK5 stains the outer cells of the dermal duct and lower intraepidermal duct but does not stain the intraepidermal duct located in the upper epidermis. RESULTS: We were able to confirm that the solid strands stained for EMA and CK5, as did the outer cells of the ductal structure. However, the solid strands did not stain with CEA. CONCLUSIONS: The results indicated that solid strands observed in syringomas originate from the outer cells of the two layers of cells that compose the lower epidermal duct or the transitional portion between the intraepidermal duct and dermal duct in the normal eccrine or apocrine structure. Thus, we surmise that a syringoma is developed by the proliferation of these cells. PMID- 22040365 TI - Rational design of 3D dendritic TiO2 nanostructures with favorable architectures. AB - Controlling the morphology and size of titanium dioxide (TiO(2)) nanostructures is crucial to obtain superior photocatalytic, photovoltaic, and electrochemical properties. However, the synthetic techniques for preparing such structures, especially those with complex configurations, still remain a challenge because of the rapid hydrolysis of Ti-containing polymer precursors in aqueous solution. Herein, we report a completely novel approach-three-dimensional (3D) TiO(2) nanostructures with favorable dendritic architectures-through a simple hydrothermal synthesis. The size of the 3D TiO(2) dendrites and the morphology of the constituent nano-units, in the form of nanorods, nanoribbons, and nanowires, are controlled by adjusting the precursor hydrolysis rate and the surfactant aggregation. These novel configurations of TiO(2) nanostructures possess higher surface area and superior electrochemical properties compared to nanoparticles with smooth surfaces. Our findings provide an effective solution for the synthesis of complex TiO(2) nano-architectures, which can pave the way to further improve the energy storage and energy conversion efficiency of TiO(2)-based devices. PMID- 22040366 TI - Countertransference feelings in one year of individual therapy: an evaluation of the factor structure in the Feeling Word Checklist-58. AB - Although countertransference phenomena have been given much attention within psychotherapy theory, single-case studies and clinical anecdotes, empirical research is still conspicuous by its absence. To assess the therapists' emotional reactions, which are understood to be part of the countertransference (CT), we used the Feeling Word Checklist 58 (Rossberg, Hoffart, & Friis, 2003); a self report questionnaire, comprising 58 feeling words. The aims of the present study were to examine the underlying factor structure and psychometric properties of these factors, and to validate the factors by exploring the relationships between countertransference feelings and the following variables: therapeutic alliance, patient personality pathology, suitability for psychodynamic therapy, interpersonal problems, level of general functioning, and symptoms. Six therapists, who treated 75 patients, with weekly, psychodynamic therapy, over 1 year, completed the checklist after each session. To establish the number of subscales in the checklist, a principal component analysis with promax rotation was conducted. The analysis revealed four clinically meaningful factors named Confident, Inadequate, Parental and Disengaged. The psychometric properties of all subscales proved to be acceptable. Alliance as reported by both patient and therapist showed differential correlations with the subscales. The patients' relational functioning showed stronger correlations with the CT feelings than the patients' symptoms and level of functioning. The four subscales found in the Feeling Word Checklist-58 seem to capture clinically meaningful aspects of the therapeutic dyad, and countertransference feelings are systematically related to different relational variables. PMID- 22040367 TI - Chemical and sensory quantification of geosmin and 2-methylisoborneol in rainbow trout (Oncorhynchus mykiss) from recirculated aquacultures in relation to concentrations in basin water. AB - Globally, aquaculture systems with water recirculation experience increasing problems with microbial taste and odor compounds (TOCs) such as geosmin and 2 methylisoborneol (MIB). This study investigated the content of geosmin and MIB in water and the flesh of 200 rainbow trouts from eight recirculated aquaculture systems in Denmark. TOC content in the fish flesh was measured by a dynamic headspace extraction method and was evaluated by a sensory panel. The results showed significant correlations between TOC content in water and fish and between chemical analysis and sensory perception. When geosmin exceeded 20 ng/L in the water, 96% of the fish had an intense muddy flavor, but below 10 ng geosmin/L, 18% of the fish (only 3% in special depuration ponds) had an intense muddy flavor. The results indicate that TOC levels <10 ng/L will ensure that a negligible portion of the fish obtains an unpalatable taste and flavor due to TOCs. PMID- 22040368 TI - Increasing incidence of invasive pneumococcal disease and pneumonia despite improved vaccination uptake: surveillance in Hull and East Yorkshire, UK, 2002 2009. AB - Introduction of pneumococcal polysaccharide (PPV23) and conjugate vaccine (PCV7) programmes were expected to change the epidemiology of invasive pneumococcal disease (IPD) and pneumonia in the UK. We describe the epidemiology of IPD and hospitalization with pneumonia using high-quality surveillance data over an 8 year period, 2002-2009. Although PPV23 uptake increased from 49% to 70% and PCV7 uptake reached 98% by 2009, the overall incidence of IPD increased from 11.8/100 000 to 16.4/100 000 (P=0.13), and the incidence of hospitalization with pneumonia increased from 143/100 000 to 207/100 000 (P<0.001). Although a reduction in the proportion of IPD caused by PCV7 serotypes was observed, concurrent increases in PPV23 and non-vaccine serotype IPD contributed to an increased IPD burden overall. Marked inequalities in the geographical distribution of disease were observed. Existing vaccination programmes have, so far, not been sufficient to address an increasing burden of pneumococcal disease in our locality. PMID- 22040369 TI - Modified Field stain - rapid viability test for Trichomonas vaginalis. AB - AIMS: We previously reported that Modified Field Stain (MF) can be used as a rapid stain for diagnosis. In the present study we extend the observation to include the stain as an alternative method to assess viability of the cells. METHODS AND RESULTS: Six isolates of Trichomonas vaginalis were used to assess the utility of the Modified Field stain as a rapid viability test for T. vaginalis and to compare with 0.4% Trypan Blue dye exclusion test in three conditions; normal in vitro culture growth using Hollander medium, lysed in distilled water and treated with metronidazole. MF stain showed similar growth profile pattern as Trypan Blue dye exclusion for identifying viable cells of T. vaginalis. Although, Trypan Blue dye exclusion test is ready made, rapid and widely used in laboratory as reliable viability assay, however, the limitation using Trypan Blue is the dye was unable to show internal morphological changes during the parasite's transition from being viable to non-viable. On day 3 where cultures peaked the correlation factor of both assays done to assess the viability of parasites harvested from the controls, metronidazole and distilled water treated parasites were more than 0.9 respectively. CONCLUSIONS: This confirms that MF staining does not only record permanently the morphological changes and retain internal structural details but also provides a reliable and rapid viability assay for the parasites. SIGNIFICANCE AND IMPACT OF THE STUDY: Therefore, in our study, Modified Field's stain may offer the researchers and laboratory technologists the opportunity to get the result on the same day and the most important thing is the ability to differentiate between viable and non viable of T. vaginalis under three different conditions (normal culture, drug and distilled water condition). Modified Field's staining method enhanced the morphological identification of T. vaginalis compared to Trypan Blue dye exclusion. PMID- 22040370 TI - Growth charts for monitoring postnatal growth at NICU of extreme preterm-born infants. AB - AIM: To provide growth charts for clinical monitoring of extra-uterine growth from birth to full-term age, in infants born before 26 weeks of gestation, hospitalized at neonatal intensive care unit (NICU), and compare it to the commonly used Swedish preterm birth-size reference. METHODS: This retrospective longitudinal cohort comprised all infants born before 26 + 0 weeks of gestation and surviving to full-term age (n = 162), admitted to the NICU, Karolinska Hospital during the period January 1990 to December 2002. Body weight was recorded daily, head circumference (HC) weekly and length twice a month. RESULTS: Birth weight (BW), length and HC showed a normal distribution without significant gender difference. The majority of the infants showed a pronounced postnatal growth restriction for all growth variables with increasing deviation from the reference with age. The mean initial weight loss was 16% with nadir at 6 days of age and a mean time to regain BW of 18 days. At discharge from NICU, 75% of those initially appropriate for gestational age infants were below -2 standard deviation scores for at least one of the body size variables. CONCLUSION: The poor extra-uterine growth pattern points to the need of growth curves for extra uterine growth of extremely premature infants. PMID- 22040371 TI - Many tests of significance: new methods for controlling type I errors. AB - There have been many discussions of how Type I errors should be controlled when many hypotheses are tested (e.g., all possible comparisons of means, correlations, proportions, the coefficients in hierarchical models, etc.). By and large, researchers have adopted familywise (FWER) control, though this practice certainly is not universal. Familywise control is intended to deal with the multiplicity issue of computing many tests of significance, yet such control is conservative--that is, less powerful--compared to per test/hypothesis control. The purpose of our article is to introduce the readership, particularly those readers familiar with issues related to controlling Type I errors when many tests of significance are computed, to newer methods that provide protection from the effects of multiple testing, yet are more powerful than familywise controlling methods. Specifically, we introduce a number of procedures that control the k FWER. These methods--say, 2-FWER instead of 1-FWER (i.e., FWER)--are equivalent to specifying that the probability of 2 or more false rejections is controlled at .05, whereas FWER controls the probability of any (i.e., 1 or more) false rejections at .05. 2-FWER implicitly tolerates 1 false rejection and makes no explicit attempt to control the probability of its occurrence, unlike FWER, which tolerates no false rejections at all. More generally, k-FWER tolerates k - 1 false rejections, but controls the probability of k or more false rejections at alpha =.05. We demonstrate with two published data sets how more hypotheses can be rejected with k-FWER methods compared to FWER control. PMID- 22040372 TI - Fitting multilevel models with ordinal outcomes: performance of alternative specifications and methods of estimation. AB - Previous research has compared methods of estimation for fitting multilevel models to binary data, but there are reasons to believe that the results will not always generalize to the ordinal case. This article thus evaluates (a) whether and when fitting multilevel linear models to ordinal outcome data is justified and (b) which estimator to employ when instead fitting multilevel cumulative logit models to ordinal data, maximum likelihood (ML), or penalized quasi likelihood (PQL). ML and PQL are compared across variations in sample size, magnitude of variance components, number of outcome categories, and distribution shape. Fitting a multilevel linear model to ordinal outcomes is shown to be inferior in virtually all circumstances. PQL performance improves markedly with the number of ordinal categories, regardless of distribution shape. In contrast to binary data, PQL often performs as well as ML when used with ordinal data. Further, the performance of PQL is typically superior to ML when the data include a small to moderate number of clusters (i.e., <= 50 clusters). PMID- 22040373 TI - The design and analysis of state-trace experiments. AB - State-trace analysis (Bamber, 1979) addresses a question of interest in many areas of psychological research: Does 1 or more than 1 latent (i.e., not directly observed) variable mediate an interaction between 2 experimental manipulations? There is little guidance available on how to design an experiment suited to state trace analysis, despite its increasing use, and existing statistical methods for state-trace analysis are problematic. We provide a framework for designing and refining a state-trace experiment and statistical procedures for the analysis of accuracy data using Klugkist, Kato, and Hoijtink's (2005) method of estimating Bayes factors. The statistical procedures provide estimates of the evidence favoring 1 versus more than 1 latent variable, as well as evidence that can be used to refine experimental methodology. PMID- 22040374 TI - Heterochrony and developmental modularity of cranial osteogenesis in lipotyphlan mammals. AB - BACKGROUND: Here we provide the most comprehensive study to date on the cranial ossification sequence in Lipotyphla, the group which includes shrews, moles and hedgehogs. This unique group, which encapsulates diverse ecological modes, such as terrestrial, subterranean, and aquatic lifestyles, is used to examine the evolutionary lability of cranial osteogenesis and to investigate the modularity of development. RESULTS: An acceleration of developmental timing of the vomeronasal complex has occurred in the common ancestor of moles. However, ossification of the nasal bone has shifted late in the more terrestrial shrew mole. Among the lipotyphlans, sequence heterochrony shows no significant association with modules derived from developmental origins (that is, neural crest cells vs. mesoderm derived parts) or with those derived from ossification modes (that is, dermal vs. endochondral ossification). CONCLUSIONS: The drastic acceleration of vomeronasal development in moles is most likely coupled with the increased importance of the rostrum for digging and its use as a specialized tactile surface, both fossorial adaptations. The late development of the nasal in shrew moles, a condition also displayed by hedgehogs and shrews, is suggested to be the result of an ecological reversal to terrestrial lifestyle and reduced functional importance of the rostrum. As an overall pattern in lipotyphlans, our results reject the hypothesis that ossification sequence heterochrony occurs in modular fashion when considering the developmental patterns of the skull. We suggest that shifts in the cranial ossification sequence are not evolutionarily constrained by developmental origins or mode of ossification. PMID- 22040375 TI - Infection after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use. PMID- 22040376 TI - Comparative genomics study of polyhydroxyalkanoates (PHA) and ectoine relevant genes from Halomonas sp. TD01 revealed extensive horizontal gene transfer events and co-evolutionary relationships. AB - BACKGROUND: Halophilic bacteria have shown their significance in industrial production of polyhydroxyalkanoates (PHA) and are gaining more attention for genetic engineering modification. Yet, little information on the genomics and PHA related genes from halophilic bacteria have been disclosed so far. RESULTS: The draft genome of moderately halophilic bacterium, Halomonas sp. TD01, a strain of great potential for industrial production of short-chain-length polyhydroxyalkanoates (PHA), was analyzed through computational methods to reveal the osmoregulation mechanism and the evolutionary relationship of the enzymes relevant to PHA and ectoine syntheses. Genes involved in the metabolism of PHA and osmolytes were annotated and studied in silico. Although PHA synthase, depolymerase, regulator/repressor and phasin were all involved in PHA metabolic pathways, they demonstrated different horizontal gene transfer (HGT) events between the genomes of different strains. In contrast, co-occurrence of ectoine genes in the same genome was more frequently observed, and ectoine genes were more likely under coincidental horizontal gene transfer than PHA related genes. In addition, the adjacent organization of the homologues of PHA synthase phaC1 and PHA granule binding protein phaP was conserved in the strain TD01, which was also observed in some halophiles and non-halophiles exclusively from gamma proteobacteria. In contrast to haloarchaea, the proteome of Halomonas sp. TD01 did not show obvious inclination towards acidity relative to non-halophilic Escherichia coli MG1655, which signified that Halomonas sp. TD01 preferred the accumulation of organic osmolytes to ions in order to balance the intracellular osmotic pressure with the environment. CONCLUSIONS: The accessibility of genome information would facilitate research on the genetic engineering of halophilic bacteria including Halomonas sp. TD01. PMID- 22040377 TI - The 'F-words' in childhood disability: I swear this is how we should think! AB - The 21st century is witnessing a sea change in our thinking about 'disability'. Nowhere are these developments more apparent than in the field of childhood disability, where traditional biomedical concepts are being incorporated into- but expanded considerably by--new ways of formulating ideas about children, child development, social-ecological forces in the lives of children with chronic conditions and their families, and 'points of entry' for professionals to be helpful. In this paper, we have tried to package a set of ideas, grounded in the World Health Organization's International Classification of Functioning, Disability and Health (the ICF), into a series of what we have called 'F-words' in child neurodisability--function, family, fitness, fun, friends and future. We hope this will be an appealing way for people to incorporate these concepts into every aspect of clinical service, research and advocacy regarding disabled children and their families. PMID- 22040378 TI - WITHDRAWN: AB - Ahead of Print article withdrawn by publisher. PMID- 22040379 TI - Strategies to facilitate the development of uncloned or cloned infectious full length viral cDNAs: Apple chlorotic leaf spot virus as a case study. AB - BACKGROUND: Approaches to simplify and streamline the construction of full-length infectious cDNA clones (FL-cDNAs) are needed. Among desirable improvements are the ability to use total nucleic acids (TNA) extracts from infected hosts (to bypass viral purification limitations) for the direct one-step amplification of large FL-cDNAs, the possibility to inoculate plants with uncloned FL-cDNAs and the simplified cloning of these large molecules. RESULTS: Using the 7.55 kb genome of Apple chlorotic leaf spot trichovirus (ACLSV) approaches allowing the rapid generation from TNA extracts of FL-cDNAs under the control of the T7 promoter and the successful inoculation of plants using in vitro transcripts obtained from these uncloned amplification products have been developed. We also show that the yeast homologous recombination system permits efficient cloning of FL-cDNAs and the simultaneous one-step tailoring of a ternary Yeast-Escherichia coli-Agrobacterium tumefaciens shuttle vector allowing efficient inoculation of both herbaceous and woody host plants by agroinfiltration. CONCLUSIONS: The fast and efficient strategies described here should have broad applications, in particular for the study of "difficult" plant viruses, such as those infecting woody hosts, and potentially for other, non plant-infecting viral agents. PMID- 22040380 TI - Small noncoding RNA modulates Japanese encephalitis virus replication and translation in trans. AB - BACKGROUND: Sequence and structural elements in the 3'-untranslated region (UTR) of Japanese encephalitis virus (JEV) are known to regulate translation and replication. We previously reported an abundant accumulation of small subgenomic flaviviral RNA (sfRNA) which is collinear with the highly conserved regions of the 3'-UTR in JEV-infected cells. However, function of the sfRNA in JEV life cycle remains unknown. RESULTS: Northern blot and real-time RT-PCR analyses indicated that the sfRNA becomes apparent at the time point at which minus-strand RNA (antigenome) reaches a plateau suggesting a role for sfRNA in the regulation of antigenome synthesis. Transfection of minus-sense sfRNA into JEV-infected cells, in order to counter the effects of plus-sense sfRNA, resulted in higher levels of antigenome suggesting that the presence of the sfRNA inhibits antigenome synthesis. Trans-acting effect of sfRNA on JEV translation was studied using a reporter mRNA containing the luciferase gene fused to partial coding regions of JEV and flanked by the respective JEV UTRs. In vivo and in vitro translation revealed that sfRNA inhibited JEV translation. CONCLUSIONS: Our results indicate that sfRNA modulates viral translation and replication in trans. PMID- 22040381 TI - Metallographic analysis and fire dynamics simulation for electrical fire scene reconstruction. AB - This study demonstrated the use of metallographic analysis and NIST's Fire Dynamics Simulator (FDS) program to identify the cause of an actual electrical fire. A severely carbonized steel plate and a cable with a bead were found inside a damaged switchboard from the debris of a factory fire. By metallographic analysis, the copper spatter on the steel plate was found to imply a short circuit has occurred and that this was the probable ignition source of the fire was supported by the presence of a small amount of copper oxide and by the cavities with the tree-like grain microstructures in the bead. The heat estimated to have been released per unit area of the switchboard in question (approximately 236.29 MJ/m(2)) served as key input data for applying the FDS simulation of the blaze. The simulation indicated that thermal insulation polyethylene (PE) played an important role in the rapid fire spread. PMID- 22040382 TI - Takotsubo cardiomyopathy after a dancing session: a case report. AB - INTRODUCTION: Stress-induced (Takotsubo) cardiomyopathy is a rare form of cardiomyopathy which presents in a manner similar to that of acute coronary syndrome. This sometimes leads to unnecessary thrombolysis therapy. The pathogenesis of this disease is still poorly understood. We believe that reporting all cases of Takotsubo cardiomyopathy will contribute to a better understanding of this disease. Here, we report a patient who, in the absence of any recent stressful events in her life, developed the disease after a session of dancing. CASE PRESENTATION: A 69-year-old Caucasian woman presented with features suggestive of acute coronary syndrome shortly after a session of dancing. Echocardiography and a coronary angiogram showed typical features of Takotsubo cardiomyopathy and our patient was treated accordingly. Eight weeks later, her condition resolved completely and the results of echocardiography were totally normal. CONCLUSIONS: Takotsubo cardiomyopathy, though transient, is a rare and serious condition. Although it is commonly precipitated by stressful life events, these are not necessarily present. Our patient was enjoying one of her hobbies (that is, dancing) when she developed the disease. This case has particular interest in medicine, especially for the specialties of cardiology and emergency medicine. We hope that it will add more information to the literature about this rare condition. PMID- 22040383 TI - Early-stage cognitive impairment in Parkinson's disease and the influence of dopamine replacement therapy. AB - BACKGROUND AND PURPOSE: The aim of this study was to establish the cognitive profile of newly diagnosed untreated (de novo) patients with Parkinson's disease (PD) and more advanced, treated patients, and to determine the effects of dopamine (DA) replacement therapy. METHODS: A cohort of 23 de novo patients, 55 mild to moderately advanced, medicated PD patients and 21 healthy controls participated. Cognitive tests included the Cambridge Examination for Mental Disorders and a battery of neuropsychological tests taken from the Cambridge Neuropsychological Test Automated Battery and the Vienna Test System. RESULTS: De novo patients with PD were more impaired in working memory strategy use than healthy controls and treated patients with PD. Furthermore, the generation of random motor behaviour was more impaired in both de novo and treated PD patients than in healthy controls. Correlation analysis revealed that in treated patients with PD, ascending doses of dopaminergic medication were associated with poorer performance on a pattern recognition task. CONCLUSION: Selective impairments in strategy use and the generation of random motor behaviour are a very early feature of PD and might be of predictive value in further frontal cognitive deterioration. Furthermore, DA replacement therapy seems to improve frontal lobe function (strategy use) and worsen temporal lobe function (visual memory). PMID- 22040384 TI - Switching in polaritonic-photonic crystal nanofibers doped with quantum dots. AB - We have studied the acousto-optic effect in polaritonic nanofibers made by embedding a cylindrical polaritonic nanowire within a photonic crystal. Here the nanowire consists of either a phonon-polaritonic or an exciton-polaritonic material. The nanowire is doped with ensemble of noninteracting quantum dots. Quantum dots interact with the nanofiber via the exciton-polariton interaction. It is found that for the certain acoustic strain intensity the nanofiber has a localized-to-delocalized polariton transition similar to the metal-to-insulator transitions in doped semiconductors. It is also found that nanofiber has a transparent state due to the exciton-bound polariton coupling. The transparent state can be switched ON or OFF by the external acoustic strain intensity. These are very useful discoveries that can be used to fabricate new types of polaritonic nanoswitches and nanosensors. PMID- 22040385 TI - Toward an image-guided microbeam radiation therapy using gadolinium-based nanoparticles. AB - Ultrasmall gadolinium-based nanoparticles (GBNs) induce both a positive contrast for magnetic resonance imaging and a radiosentizing effect. The exploitation of these characteristics leads to a greater increase in lifespan of rats bearing brain tumors since the radiosensitizing effect of GBNs can be activated by X-ray microbeams when the gadolinium content is, at the same time, sufficiently high in the tumor and low in the surrounding healthy tissue. GBNs exhibit therefore an interesting potential for image-guided radiotherapy. PMID- 22040386 TI - Comparison of native and capric acid-enriched mustard oil effects on oxidative stress and antioxidant protection in rats. AB - The present study evaluated the effect of mustard oil enriched in capric acid, a medium-chain fatty acid, on antioxidant enzyme activities in liver and brain and on the levels of malondialdehyde (MDA) in liver, brain and plasma in rats; the effect of adding cholesterol to the diet was also investigated. Charles Foster male albino rats weighing 80-100 g were fed one of four diets for 30 d (six rats per group). In the absence of added dietary cholesterol, the addition of capric acid to the diet resulted in lower plasma total cholesterol, non-HDL-cholesterol and TAG concentrations, higher HDL-cholesterol concentrations, higher antioxidant enzyme activities in liver and brain and lower MDA concentrations in liver, brain and plasma. Adding cholesterol to the diet increased plasma total cholesterol, non-HDL-cholesterol and TAG concentrations, decreased HDL-cholesterol concentration, decreased the activities of antioxidant enzymes and increased tissue and plasma MDA concentrations. Including capric acid in the diet of rats receiving cholesterol at least partly prevented the effects of the increased cholesterol. It is concluded that compared with native mustard oil, capric acid enriched mustard oil improves blood lipids, enhances antioxidant protection and reduces lipid peroxidation. PMID- 22040387 TI - The potential for web-based social network sites and self-regulation for health promotion. PMID- 22040388 TI - Randomized trial of a computer-tailored intervention for patients with depression. AB - PURPOSE. Examine the efficacy of a computer-tailored intervention (CTI) based on the transtheoretical model (TTM) for reducing depression, an increasingly important component of health promotion programs. DESIGN. Pretest-posttest randomized trial. Setting . Participants were recruited and treated at home after being identified in two primary care clinics in Eastern Massachusetts and Chicago, Illinois. SUBJECTS. A total of 350 adults experiencing at least mild symptoms of depression but not involved in or planning to seek treatment for depression. INTERVENTION. A print manual and three CTI reports tailored to stage of change for using effective methods to prevent or reduce depression, other TTM variables, level of depression, and behavior. . Pre-post changes and reliable and clinically significant change on the Beck Depression scale II and pre-post changes on the 20-item Medical Outcomes Study Short Form survey-based measure of physical functioning at 9 months' follow-up. ANALYSIS. t-tests and chi(2) tests. Complete-case analysis and two intention-to-treat analyses-assumption of no change and multiple imputation (MI)-are reported. Exploratory analyses examined whether the effects of the intervention on depression were moderated by five subject characteristics: baseline level of depression, baseline level of physical functioning, baseline stage of change for preventing or managing depression, age, and education. RESULTS. Complete-case and intention-to-treat analyses showed that the intervention group experienced significantly greater improvements in depression (d = .220-.355); results for physical functioning were weaker (d = .150-.309) and did not reach statistical significance in the MI analysis. The effects of the intervention on reliable and clinically significant change in depression were largest among participants who were experiencing moderate depression (d = .363-.519) or severe depression (d = .603-.718) or who were in the precontemplation or contemplation stage (d = .573-.856) at baseline. PMID- 22040389 TI - Assessing digital literacy in web-based physical activity surveillance: the WIN study. AB - PURPOSE. Investigate relations between demographic characteristics and submission method, Internet or paper, when physical activity behaviors are reported. DESIGN. Observational. SETTING . Metropolitan. SUBJECTS. Adult women (N = 918) observed weekly for 2 years (total number of weekly reports, 44,963). MEASURES. Independent variables included age, race, education, income, employment status, and Internet skills. Dependent variables were method of submission (Internet or paper) and adherence. ANALYSIS . Logistic regression to analyze weekly odds of submitting data online and meeting study adherence criteria. Model 1 investigated method of submission, model 2 analyzed meeting study's Internet adherence, and model 3 analyzed meeting total adherence regardless of submission method. RESULTS. Whites, those with good Internet skills, and those reporting higher incomes were more likely to log online. Those who were white, older, and reported good Internet skills were more likely to be at least 75% adherent online. Older women were more likely to be adherent regardless of method. Employed women were less likely to log online or be adherent. CONCLUSION . Providing participants with multiple submission methods may reduce potential bias and provide more generalizable results relevant for future Internet-based research. PMID- 22040390 TI - Community capacity as an "inside job": evolution of perceived ownership within a university-aboriginal community partnership. AB - PURPOSE. To assess the evolution of perceived ownership of a university Aboriginal community partnership across three project stages. DESIGN. Survey administration to project partners during project formalization (1996-T1), mobilization (1999-T2), and maintenance (2004-T3). SETTING. Aboriginal community of Kahnawake, outside Montreal, Quebec, Canada. PARTICIPANTS. Partners involved in influencing decision making in the Kahnawake Schools Diabetes Prevention Project (KSDPP). MEASURE AND ANALYSIS . A measure of perceived primary ownership subjected to linear trend analysis. RESULTS. KSDPP staff were perceived as primary owner at T1 and shared ownership with Community Advisory Board (CAB) members at T2 and T3. Trend tests indicated greater perceived ownership between T1 and T3 for CAB (chi(2)(1) = 12.3, p < .0001) and declining KSDPP staff (chi(2)(1) = 10.5, p < .001) ownership over time. Academic partners were never perceived as primary owners. CONCLUSION. This project was community driven from the beginning. It was not dependent on an external academic change agent to activate the community and develop the community's capacity to plan and implement a solution. It still took several years for the grassroots CAB to take responsibility from KSDPP staff, thus indicating the need for sustained funding to build grassroots community capacity. PMID- 22040391 TI - Health risk behaviors of Afghanistan and Iraq war veterans attending college. AB - PURPOSE. The population of military veterans attending college is rapidly growing as veterans return from Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF). We sought to describe patterns of student veterans' health-related behaviors and how they might differ from their nonveteran peers. DESIGN. We analyzed data from the 2008 Boynton College Student Health Survey (CSHS). SETTING. CSHS participants completed an anonymous online survey. SUBJECTS. The CSHS sampled students (n = 8651) attending public, private, 2-year, and 4-year postsecondary educational institutions in Minnesota. MEASURES. The CSHS included items on substance use (including alcohol and tobacco), safety, nutrition, and physical activity. ANALYSIS. We described demographics of OEF/OIF veteran, non OEF/OIF veteran, and nonveteran students and used Poisson regression to compute adjusted relative risks (ARRs) with 95% confidence intervals (CIs) to characterize associations between veteran status and health behaviors. RESULTS. After controlling for demographics, veteran students reported more safety-, tobacco-, and alcohol-related risk behaviors compared to nonveteran students. For instance, compared to the nonveteran reference group, the ARR for past year smokeless tobacco use and physical fighting among for OEF/OIF veterans was 1.76 (95% CI = 1.31-2.35) and 1.48 (95% CI = 1.22-1.79) respectively. Veteran and nonveteran students display similar weight-related behaviors, though OEF/OIF veteran students were more likely to engage in strengthening exercises. CONCLUSIONS. There are specific health risk behaviors that are particularly relevant for veterans attending postsecondary institutions. As veterans enroll in postsecondary education, there is a unique window of opportunity for health promotion in this population. PMID- 22040392 TI - An examination of the relationship between neighborhood income inequality, social resources, and obesity in Los Angeles county. AB - PURPOSE. This study examines whether local income inequality is associated with an increased likelihood of obesity among Los Angeles County residents and whether collective efficacy mediates the relationship. DESIGN. A cross-sectional study of 2875 adults in 65 neighborhoods that took part in wave 1 of the Los Angeles Family and Neighborhood Survey in 2000-2001. Neighborhood measures are taken from the Los Angeles Neighborhood Services and Characteristics Database and decennial census. MEASURES. Obesity is defined as a body mass index over 30. Income inequality is operationalized with the Gini coefficient. Collective efficacy is a neighborhood-level measure comprised of aggregated responses to items that capture trust, cohesion, and the willingness to intervene for the common good among residents. Controls are included at the individual level for demographics and health characteristics, and at the neighborhood level for median household income. ANALYSIS. Logistic regression models of individuals within neighborhoods. RESULTS. When neighborhood economic well-being is controlled, income inequality is associated with a significant reduction in the likelihood of obesity while also controlling for individual demographic and health-related characteristics. Collective efficacy exerts an independent and beneficial effect but does not mediate the relationship between inequality and obesity. CONCLUSION. Neighborhood social resources and economic heterogeneity are associated with a lower likelihood of obesity. It may be that economically heterogeneous neighborhoods, perhaps especially in Los Angeles County, contain characteristics that promote health. PMID- 22040393 TI - Improving data accuracy of commercial food outlet databases. AB - PURPOSE. Assessing food environments often requires using commercially available data. Disparate methods used for classifying food outlets in these databases call for creating a classification approach using common definitions. A systematic strategy for reclassifying food stores and restaurants, as they appear in commercial databases, into categories that differentiate the availability of healthy options is described here. DESIGN AND SETTING. Commercially available data on food outlets including names, addresses, North American Industry Classification System codes, and associated characteristics was obtained for five New Jersey communities. ANALYSIS. A reclassification methodology was developed using criteria and definitions from the literature to categorize food outlets based on availability of healthy options. Information in the database was supplemented by systematic Internet and key word searches, and from phone calls to food outlets. RESULTS. The methodology resulted in 622 supermarket/grocery stores, 183 convenience stores, and 148 specialty stores in the original data to be reclassified into 58 supermarkets, 30 grocery stores, 692 convenience stores, and 115 specialty stores. Outlets from the original list of 1485 full-service restaurants and 506 limited-service restaurants were reclassified as 563 full service restaurants and 1247 limited-service restaurants. Reclassification resulted in less than one-seventh the number of supermarkets and grocery stores, more than three times the number of convenience stores, and twice as many limited service restaurants-a much less healthy profile than the one generated by using exclusively the commercial databases. CONCLUSION. An explicit and replicable strategy is proposed for reclassifying food outlets in commercial databases into categories that differentiate on the basis of healthy food availability. The intent is to contribute towards building a consensus among researchers on definitions used in public health research for characterizing different types of food outlets. PMID- 22040397 TI - Development and implementation of the guiding stars nutrition guidance program. AB - PURPOSE . To describe the collaborative process between a grocery retailer and a panel of nutrition experts used to develop a nutrition guidance system (Guiding Stars) that evaluates the nutrient profile of all edible products in the supermarket, and to report the results of the food and beverage ratings. DESIGN . A collaboration between a private retailer and members of the scientific community that led to the development of a scoring algorithm used to evaluate the nutritional quality of foods and beverages. SETTING/SUBJECTS . Northeast supermarkets (n = 160). MEASURES . Food and beverage nutrition ratings and distribution of stars across different grocery categories. ANALYSIS . Descriptive statistics for rating distributions were computed. T-tests were conducted to assess differences in mean nutrient values between foods with zero versus three stars or a dichotomized variable representing all foods with one to three stars. RESULTS . All edible grocery items (n = 27,466) were evaluated, with 23.6% earning at least one star. Items receiving at least one star had lower mean levels of sodium, saturated fat, and sugars and higher amounts of fiber than products not earning stars. CONCLUSION . The Guiding Stars system rates edible products without regard to brand or manufacturer, and provides consumers with a simple tool to quickly identify more nutritious choices while shopping. The low percentage of products qualifying for stars reflects poorly on the food choices available to Americans. PMID- 22040398 TI - The ACTIVATE study: results from a group-randomized controlled trial comparing a traditional worksite health promotion program with an activated consumer program. AB - PURPOSE. This study compares a traditional worksite-based health promotion program with an activated consumer program and a control program DESIGN. Group randomized controlled trial with 18-month intervention. SETTING. Two large Midwestern companies. SUBJECTS. Three hundred and twenty employees (51% response). INTERVENTION. The traditional health promotion intervention offered population-level campaigns on physical activity, nutrition, and stress management. The activated consumer intervention included population-level campaigns for evaluating health information, choosing a health benefits plan, and understanding the risks of not taking medications as prescribed. The personal development intervention (control group) offered information on hobbies. The interventions also offered individual-level coaching for high risk individuals in both active intervention groups. MEASURES. Health risk status, general health status, consumer activation, productivity, and the ability to evaluate health information. ANALYSIS. Multivariate analyses controlled for baseline differences among the study groups. RESULTS. At the population level, compared with baseline performance, the traditional health promotion intervention improved health risk status, consumer activation, and the ability to recognize reliable health websites. Compared with baseline performance, the activated consumer intervention improved consumer activation, productivity, and the ability to recognize reliable health websites. At the population level, however, only the activated consumer intervention improved any outcome more than the control group did; that outcome was consumer activation. At the individual level for high risk individuals, both traditional health coaching and activated consumer coaching positively affected health risk status and consumer activation. In addition, both coaching interventions improved participant ability to recognize a reliable health website. Consumer activation coaching also significantly improved self-reported productivity. CONCLUSION. An effective intervention can change employee health risk status and activation both at the population level and at the individual high risk level. However, program engagement at the population level was low, indicating that additional promotional strategies, such as greater use of incentives, need to be examined. Less intensive coaching can be as effective as more intensive, albeit both interventions produced modest behavior change and retention in the consumer activation arm was most difficult. Further research is needed concerning recruitment and retention methods that will enable populations to realize the full potential of activated consumerism. PMID- 22040399 TI - Environmental influences on children's physical activity and eating habits in a rural Oregon County. AB - PURPOSE. To identify environmental barriers and facilitators of children's physical activity and healthy eating in a rural county. DESIGN. Community-based participatory research using mixed methods, primarily qualitative. SETTING. A rural Oregon county. SUBJECTS. Ninety-five adults, 6 high school students, and 41 fifth-grade students. MEASURES. In-depth interviews, focus groups, Photovoice, and structured observations using the Physical Activity Resource Assessment, System for Observing Play and Leisure Activity, Community Food Security Assessment Toolkit, and School Food and Beverage Marketing Assessment Tool. ANALYSIS. Qualitative data were coded by investigators; observational data were analyzed using descriptive statistics. The findings were triangulated to produce a composite of environmental barriers and assets. RESULTS. Limited recreational resources, street-related hazards, fear of strangers, inadequate physical education, and denial of recess hindered physical activity, whereas popularity of youth sports and proximity to natural areas promoted physical activity. Limited availability and high cost of healthy food, busy lifestyles, convenience stores near schools, few healthy meal choices at school, children's being permitted to bring snacks to school, candy used as incentives, and teachers' modeling unhealthy eating habits hindered healthy eating, whereas the agricultural setting and popularity of gardening promoted healthy eating. CONCLUSIONS. This study provides data on a neglected area of research, namely environmental determinants of rural childhood obesity, and points to the need for multifaceted and multilevel environmental change interventions. PMID- 22040400 TI - Can we reduce our federal deficit and create jobs by making the healthy choice the easiest choice? PMID- 22040401 TI - Integrating wellness into hospital systems. PMID- 22040402 TI - Thiolated glycol chitosan bearing alpha-cyclodextrin for sustained delivery of PEGylated human growth hormone. AB - The extensive use of human growth hormone (hGH), emerging as protein therapeutics, has been limited by its instability in biological fluids and short biological half-life. In this study, thiolated glycol chitosan bearing alpha cyclodextrin (TGC-CD), in situ cross-linked by poly(ethylene glycol)-diacrylate (PEG-DA), was synthesized to develop a sustained release system for PEGylated hGH (PEG-hGH). TGC-CD could form a stable inclusion complex with PEG-hGH by the physical interaction between the inner cavity of CD and PEG. Such a complex was readily cross-linked in the presence of PEG-DA via a Michael-type addition reaction. From the in vitro release experiments of PEG-hGH, it was confirmed that PEG-hGH was completely released from the complex for 12 h in PBS (pH 7.4), whereas the release rate of PEG-hGH was significantly reduced by the chemical cross-linking of the complex. PEG-hGH, released from the cross-linked complexes, maintained its structural integrity, which was demonstrated using circular dichroism spectroscopy. Overall, TGC-CD might be useful for sustained delivery of PEG-hGH. PMID- 22040403 TI - Evaluation of the efficacy of a prosthodontic stent in determining the position of dental implants. AB - PURPOSE: To evaluate the efficacy of a dual purpose (diagnostic and surgical) acrylic resin stent with gutta percha marker used in conjunction with 3D imaging in determination of the position and inclination of dental implants. MATERIALS AND METHODS: This study was performed as a case control study. A total of 41 implants, of which 20 had been placed without the use of stents and 3D imaging (control group) and 21 were placed using stents and 3D imaging (study group), were studied. A diagnostic and surgical stent with radio-opaque indicator (gutta percha) was fabricated to determine the planned prosthetic position and inclination of the implant. Computed tomography images were obtained and were analyzed using Denta Scan software. The position of the implant was analyzed in mesiodistal and buccolingual dimensions in terms of both position and angulation. SPSS v15.0 was used for statistical analysis (p < 0.05 was considered statistically significant). RESULTS: The study group demonstrated an overall 98.9% efficacy of the test technique being used in the study. On qualitative assessment, the results obtained were within the defined ideal threshold level for four of five parameters (distance from buccal and lingual cortical plate, inter-implant distance, and buccolingual angulation of the implant relative to underlying alveolar bone). For mesiodistal distance from adjacent teeth, the observation was not above threshold value for only one case. For the control group, the overall efficacy was 66.9%. CONCLUSION: The technique of combined use of a prosthodontic stent and 3D imaging is an efficacious and better technique in achieving an ideal position of dental implants as compared to conventional techniques using periapical and panoramic radiographs and a cast. PMID- 22040404 TI - Oncogene addiction and non-oncogene addiction in glioblastoma therapy. PMID- 22040405 TI - Current status of cerebral glioma surgery in China. AB - The treatment of gliomas is highly individualized. Surgery for gliomas is essentially for histological diagnosis, to alleviate mass effect, and most importantly, to favor longer survival expectancy. During the past two decades, many surgical techniques and adjuvants have been applied to glioma surgery in China, which lead to a rapid development in the field of cerebral glioma surgery. This article broadly and critically reviewed the existing studies on cerebral glioma surgery and to portrait the current status of glioma surgery in China. A literature search was conducted covering major innovative surgical techniques and adjuvants for glioma surgery in China. The following databases were searched: the Pubmed (January 1995 to date); China Knowledge Resource Integrated Database (January 1995 to date) and VIP Database for Chinese Technical Periodicals (January 1995 to date). A selection criterion was established to exclude duplicates and irrelevant studies. The outcome measures were extracted from included studies. A total of 3307 articles were initially searched. After excluded by abstracts and full texts, 69 studies conducted in the mainland of China were included and went through further analysis. The philosophy of surgical strategies for cerebral gliomas in China is undergoing tremendous change. Nowadays Chinese neurosurgeons pay more attention to the postoperative neurofunctional status of the patients. The aim of the glioma surgery is not only the more extensive tumor resection but also the maximal safety of intervention. The well balance of longer overall survival and higher quality of life should be judged with respect to each individual patient. PMID- 22040406 TI - Prevalence estimates for primary brain tumors in China: a multi-center cross sectional study. AB - BACKGROUND: Although the first leading cause of death in China was malignant neoplasms (mortality, 374.1 per 100,000 person-years), the full impact of primary brain tumors (PBT) on the healthcare system is not completely described because there are a few well documented reports about the epidemiologic features of brain tumors. This study aimed to report a comprehensive assessment on the prevalence of PBT. METHODS: A multicenter cross-sectional study on brain tumor (MCSBT) in China was initiated in five regional centers: Daqing (northeast), Puyang (north of China), Shiyan (center of China), Ma'anshan (center of China) and Shanghai (southeast). Prevalence rate was calculated by counting the number of people living with a PBT between October 1, 2005 and September 30, 2006 and dividing by the total population of the five communities at January 1, 2006. Estimates of prevalence were expressed as percentages and grouped according to gender and to age in fifteen-year categories. Within these strata, the rates were estimated with 95% confidence intervals (CI) using the accurate calculation of CI for Poisson distribution. A chi-square test was used to compare the various frequencies with alpha < 0.05. Age-standardized prevalence with the direct method was calculated with the ten-year age-specific prevalence and the age distribution of the Chinese population in 2010, obtained from World population prospects: the 2008 revision. RESULTS: We estimated that the overall prevalence of PBT was 24.56 per 100,000 (95%CI, 14.85 to 34.27), and the overall prevalence of PBT in female population (30.57 per 100,000 and its 95%CI ranged from 19.73 to 41.41) was higher than that in male population (18.84 per 100,000 and its 95%CI ranged from 10.33 to 27.35). However, the discrepancy between genders was not statistically significant because the 95%CI overlapped. Of 272 cases of newly diagnosed PBT, the proportion of histological subtypes by age groups, gender was statistically different (chi(2) = 52.6510, P < 0.0001). More than half of all reported tumors (52.57%) were either gliomas or meningiomas. For the youngest (aged from 0 - 19) strata of the population, glioma appeared to occur more than other subtypes, accounting for 55.56% of all of cases. The majority of brain tumors presented in those aged from 20 to 59 years was pituitary adenomas (45.12%) and gliomas (31.10%). Opposed to brain tumors in adults and teenage, gliomas only accounted for 22.22%. Meanwhile, the median ages at diagnosis of the patients with PBT were similar between males and females except for pituitary adenomas (male: 59 years old; female: 45 years old). CONCLUSIONS: Age standardized prevalence of PBT is 22.52 per 100,000 (95%CI, 13.22 to 31.82) for all populations, 17.64 per 100,000 (95%CI, 9.41 to 25.87) for men, and 27.94 per 100,000 (95%CI, 17.58 to 38.30) for women. Age standardization to China's 2010 population yielded an estimated population of 304 954 cases with PBT. Our prevalence estimates provide a conservative basis on which to plan health care services and to develop programmatic strategies for surviving. In the future, it would be helpful to have long-term observed survival rates that would make the assumptions and the resulting imprecision in the current estimates unnecessary. PMID- 22040407 TI - Gene expression profiling reveals Ki-67 associated proliferation signature in human glioblastoma. AB - BACKGROUND: Everlasting cellular proliferation is the fundamental feature during gliomagenesis and Ki-67 is one of the classical proliferation markers in human glioblastoma multiforme (GBM). However, the driver genes or core pathways for cellular proliferation in GBM have not been elucidated systematically. METHODS: We evaluated by immunohistochemistry the prognostic value of Ki-67 expression in the clinical outcome of 156 Chinese patients with GBM and a total of 64 GBM samples were selected for further Agilent genome-wide microarray analysis. On the basis of the microarray data from Tiantan (n = 64) and The Cancer Genome Atlas (TCGA) (n = 202) database, differentially expressed genes between the GBM subgroups with high or low level of Ki-67 expression were identified using Significance Analysis of Microarrays (SAM). Gene Ontology (GO) and KEGG Pathway analyses were then undertaken for the Ki-67 associated genes to identify the most significant biological processes and signaling pathways. RESULTS: We confirmed that Ki-67 was an independent prognostic indicator in the largest Chinese patient cohort of 156 GBM samples via immunohistochemical staining. Survival analysis of Ki-67 over-expression revealed a highly significant association with a worse clinical outcome (P = 0.010 for progression-free survival; P = 0.007 for overall survival). Comparative and integrated analysis between Tiantan and TCGA database identified a 247-gene "proliferation signature" (205 up-regulated and 42 down regulated genes) that distinguished Ki-67 expression phenotypes. GO and KEGG Pathway analyses further indicated that Ki-67 expression phenotype was associated with distinct changes in gene expression associated with the regulation of cellular growth and proliferation. CONCLUSIONS: Proliferation marker Ki-67 is an independent prognostic indicator in Chinese GBM patients. And Ki-67 associated proliferation signature identified through genome-wide microarray analysis may provide potential targets for anti-proliferation therapy in GBM. PMID- 22040408 TI - Relationship between magnetic resonance imaging and molecular pathology in patients with glioblastoma multiforme. AB - BACKGROUND: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor in adults. Magnetic resonance imaging (MRI) is routinely used in the diagnosis, characterization and clinical management of GBM. The diagnosis and treatment of GBM is largely guided by histopathology and immunohistochemistry. This study aimed to identify the relationship between magnetic resonance features and molecular pathology of GBM. METHODS: MRI images of 43 glioblastoma patients were collected. Four imaging features, degree of edema, contrast tumor enhanced/T2 ratio, multiple lesions and tumor across the midline, were selected to identify their relationship with P53, Ki-67 and O(6)-methylguanine-DNA methyltransferase (MGMT) expression in patients with GBM. The relationship between imaging features and molecular pathology was studied by chi-square test using the software SPSS 13.0. RESULTS: High expression of P53 was found correlated with low contrast tumor enhanced/T2 ratio, low expression of Ki-67 was correlated with multiple lesions and high expression of KI-67 may be related with tumor across the midline, low expression of MGMT was correlated with edema. CONCLUSION: Some MRI features such as the degree of edema, contrast tumor enhanced/T2 ratio, multiple lesions and tumor acrossing the midline are correlated with P53, Ki-67 and MGMT of GBM. PMID- 22040409 TI - Emotion and cognitive function assessment of patients with central neurocytoma resection through transcortical frontal approach: a 5-year postoperative follow up study. AB - BACKGROUND: Central neurocytoma accounts for 0.1% of primary brain tumor that often occurs in young adults. Surgery is the main treatment for central neurocytoma and the rate of 5-year survival reaches up to over 90%. This study aimed to assess the effect of transcortical frontal approach to surgical resection of central neurocytoma on emotion and cognitive function 5 years after surgery. METHODS: Telephone following-up visits were used in this study. By means of neuropsychological testing, assayed emotion, memory and abstract thinking ability of 18 patients undergoing central neurocytoma resection by transcortical frontal approach for 5 years or more, with another 21 normal cases as control group were enrolled. The data were analyzed statistically by paired t test with SPSS11.5. RESULTS: Patients whose central neurocytoma was removed by transcortical frontal approach were not affected on calculating ability 5 years after operation while ability of memory declined sharply (P = 0.000), the older, the more sharply (P = 0.036). Ability of abstract thinking was significantly reduced (P = 0.000), the older, the more significantly as well (P = 0.012); additionally, anxiety and depression occurred in patients rather more than those of control group (P = 0.000), especially cognitive impairment. CONCLUSIONS: Transcortical frontal approach for surgical resection of central neurocytoma has certain long-term influence on patients' life quality, vulnerable to anxiety, depression and cognitive impairment, the severity of which was correlated to age. Therefore, improving surgical approach will be of value for better long-term life quality of patients. PMID- 22040410 TI - Enhanced invasion in vitro and the distribution patterns in vivo of CD133+ glioma stem cells. AB - BACKGROUND: Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies, it is not clear whether cancer stem cells are involved in invasiveness. This study aimed to assess invasive ability of glioma stem cells (GSCs) derived from C6 glioma cell line and the distribution patterns of GSCs in Sprague-Dawley (SD) rat brain tumor. METHODS: Serum-free medium culture and magnetic isolation were used to gain purely CD133(+) GSCs. The invasive ability of CD133(+) and CD133(-) C6 cells were determined using matrigel invasion assay. Immunohistochemical staining for stem cell markers and luxol fast blue staining for white matter tracts were performed to show the distribution patterns of GSCs in brain tumor of rats and the relationship among GSCs, vessels, and white matter tracts. The results of matrigel invasion assay were estimated using the Student's t test and the analysis of Western blotting was performed using the one-way analysis of variance (ANOVA) test. RESULTS: CD133(+) GSCs (number: 85.3 +/- 4.0) were significantly more invasive in vitro than matched CD133(-) cells (number: 25.9 +/- 3.1) (t = 14.5, P < 0.005). GSCs invaded into the brain diffusely and located in perivascular niche of tumor-brain interface or resided within perivascular niche next to white fiber tracts. The polarity of glioma cells containing GSCs was parallel to the white matter tracts. CONCLUSIONS: Our data suggest that CD133(+) GSCs exhibit more aggressive invasion in vitro and GSCs in vivo probably disseminate along the long axis of blood vessels and transit through the white matter tracts. The therapies targeting GSCs invasion combined with traditional glioblastoma multiforme therapeutic paradigms might be a new approach for avoiding malignant glioma recurrence. PMID- 22040411 TI - Silencing of MGMT with small interference RNA reversed resistance in human BCUN resistant glioma cell lines. AB - BACKGROUND: Our previous study had cloned two glioma cell lines SWOZ1 and SWOZ2 isolated from parental glioma cell line SWO38. The 1,3-bis(2-chloroethyl)-1 nitrosourea (BCNU) resistance of SWOZ1 was higher than that of SWOZ2. Since O6 methylguanine-DNA methyltransferase (MGMT) was thought to be closely related to BCNU resistance in glioma, this study aimed to explore the function of MGMT in glioma resistant to BCNU. METHODS: A BCNU resistant glioma cell line SWOZ2-BCNU was established. The expression of MGMT was detected in SWOZ1, SWOZ2 and SWOZ2 BCNU. Small interferencing RNA targeting MGMT was used to silence the expression of MGMT in resistant cell lines SWOZ1 and SWOZ2-BCNU. The cytotoxicity of BCNU to these cells was measured using the cell counting kit-8 assay. Statistical analysis was carried out by one-way analysis of variance in statistical package SPSS 13.0. RESULTS: The resistance of SWOZ1 and SWOZ2-BCNU against BCNU was 4.9 fold and 5.3-fold higher than that of SWOZ2. The results of quantitative RT-PCR and Western blotting confirmed that MGMT was both significantly increased in SWOZ1 and SWOZ2-BCNU compared to SOWZ2. After transfection with small interferencing RNA targeting MGMT, a decreased level of MGMT mRNA expression in SWOZ1 and SWOZ2-BCNU for more than 75% compared to negative control was found and confirmed by Western blotting. As a result, the resistance against BCNU was reversed for about 50% both in the BCNU-resistant cell lines SWOZ1 and SWOZ2 BCNU. CONCLUSIONS: Silencing MGMT with specific small interferencing RNA can reverse the BCNU resistant phenotype in these glioma cell lines. MGMT may play an important role both in intrinsic and acquired BCNU-resistance in glioma. PMID- 22040412 TI - Virtual mutagenesis of isocitrate dehydrogenase 1 involved in glioblastoma multiforme. AB - BACKGROUND: Site A132Arg mutations potentially impair the affinity of isocitrate dehydrogenase 1 (IDH1) for its substrate isocitrate (ICT), consequently reducing the production of alpha-ketoglutarate and leading to tumor growth through the induction of the hypoxia-inducible factor-1 (HIF-1) pathway. However, given that the roles of other active sites in IDH1 substrate binding remain unclear, we aimed to investigate IDH1 mutation pattern and its influence on enzyme function. METHODS: Fifteen IDH1 catalytic active site candidates were selected for in silico mutagenesis and protein homology modeling. Binding free energy of the IDH1/ICT complexes with single-site mutations was compared with that of the wild type. The affinity of 10 IDH1 catalytic active sites for the ICT substrate was further calculated. RESULTS: The IDH1 active site included seven residues from chain A (A77Thr, A94Ser, A100Arg, A132Arg, A109Arg, A275Asp, and A279Asp) and three residues from chain B (B214Thr, B212Lys, and B252Asp) that constituted the substrate ICT-binding site. These residues were located within 0.5 nm of ICT, indicating a potential interaction with the substrate. IDH1 changes of binding free energy (DeltaE) suggested that the A132Arg residue from chain A contributes three hydrogen bonds to the ICT alpha-carboxyl and beta-carboxyl groups, while the other nine residues involved in ICT binding form only one or two hydrogen bonds. Amino acid substitutes at A132Arg, A109Arg, and B212Lys sites, had the greatest effect on enzyme affinity for its substrate. CONCLUSIONS: Mutations at sites A132Arg, A109Arg, and B212Lys reduced IDH1 affinity for ICT, indicating these active sites may play a central role in substrate binding. Mutations at sites A77Thr, A94Ser, and A275Asp increased the affinity of IDH1 for ICT, which may enhance IDN1 catalytic activity. Mutant IDH1 proteins with higher catalytic activity than the wild-type IDH1 could potentially be used as a novel gene therapy for glioblastoma multiforme. PMID- 22040413 TI - MicroRNA-7 regulates glioblastoma cell invasion via targeting focal adhesion kinase expression. AB - BACKGROUND: Invasion growth is the most characteristic biological phenotype of glioblastoma, but the molecular mechanism in glioma cell invasion is poorly understood. Recent data have showed that microRNA plays an essential role in tumor invasion. Our study aimed to explore the mechanism of miR-7 involved in the control of glioblastoma cell invasion. METHODS: Glioma cell invasion was evaluated by transwell and scratch assays after up-regulation of miR-7 using miR 7 mimics in U87 and U251 cells. Luciferase reporter assay was used to determine focal adhesion kinase (FAK) as a target of miR-7. The levels of miR-7, matrix metalloproteinases (MMP)-2 and MMP-9 mRNA were detected by PCR assay, and the levels of FAK, MMP-2, MMP-9, total and phosphorylation serine/threonine kinase (AKT), and extracellular signal-regulated kinase (ERK) 1/2 were measured by Western blotting analysis. RESULTS: Over-expression of miR-7 inhibited the invasion and migration activity of U87 and U251 cells. And up-regulation of miR-7 reduced FAK protein expression, Further, luciferase reporter assay showed that miR-7 modulated FAK expression directly by binding 3'UTR of FAK mRNA. In addition, miR-7 repressed p-ERK1/2 and p-AKT level, MMP-2 and MMP-9 expression. Finally, the inverse relationship between FAK and miR-7 expression was certificated in human glioma tissues. CONCLUSION: To our knowledge, these data indicate for the first time that miR-7 directly regulates cell invasion by targeting FAK in glioblastoma and that miR-7 could be a potential therapeutic target for glioblastoma intervention. PMID- 22040414 TI - Changes of glucocorticoid receptor mRNA expression in basolateral amygdale kindled rats. AB - BACKGROUND: Glucocorticoid receptor (GR) is believed to be a major factor in brain maturation and in modulation of a series of brain activity. Hippocampal neurons are abundant in glucocorticoid receptor, and there is significant change in GR expression under certain pathological state. Epilepsy is a special pathological state of the central nervous system. This study aimed to explore the role of GR in epilepsy by observing the change and functions of GR in hippocampus with a basolateral amygdale-electrical kindled rat epilepsy model. METHODS: Firstly, we established the basolateral amygdale-electrical kindled rat epilepsy model. Then GR mRNA expression in the hippocampus was assayed by semi quantitative reverse transcription-PCR in this experiment. In addition, the processes of epileptic seizures were observed and electroencephalograms were recorded. One-way analysis of variance (ANOVA) was employed for comparing means of multiple groups, followed Fisher's least significant difference (LSD) for paired comparison. RESULTS: The rats were successfully kindled after an average of (13.50 +/- 3.99) times electrical stimulation, in which it was showed that GR mRNA expression reduced obviously as compared with the control group and the sham groups (P < 0.001). The down-regulation of GR mRNA expression was abated or reversed by some anti-epilepsy drugs (P < 0.001 compared with the epilepsy group), accompanied by attenuation of seizures and improvement of electroencephalograms. CONCLUSIONS: Down-regulation of hippocampal GR mRNA expression may be related to the kindling. Anti-epilepsy drugs exposure can retard this change. PMID- 22040415 TI - 1,5-dicaffeoylquinic acid protects primary neurons from amyloid beta 1-42-induced apoptosis via PI3K/Akt signaling pathway. AB - BACKGROUND: Recently, 1,5-dicaffeoylquinic acid (1,5-DQA), a caffeoylquinic acid derivative isolated from Aster scaber, was found to have neuroprotective effects. However, the protective mechanisms of 1,5-DQA have not yet been clearly identified. The purpose of this study was to explore the protective mechanisms of 1,5-DQA on neuronal culture. METHODS: We investigated the neuroprotective effects of 1,5-DQA against amyloid beta(1-42) (Abeta(42))-induced neurotoxicity in primary neuronal culture. To evaluate the neuroprotective effects of 1,5-DQA, primary cultured cortical neurons from neonate rats were pretreated with 1,5-DQA for 2 hours and then treated with 40 umol/L Abeta(42) for 6 hours. Cell counting kit-8, Hoechst staining and Western blotting were used for detecting the protective mechanism. Comparisons between two groups were evaluated by independent t test, and multiple comparisons were analyzed by one-way analysis of variance (ANOVA). RESULTS: 1,5-DQA treated neurons showed increased neuronal cell viability against Abeta(42) toxicity in a concentration-dependent manner, both phosphoinositide 3-kinase (PI3K)/Akt and extracellular regulated protein kinase 1/2 (Erk1/2) were activated by 1,5-DQA with stimulating their upstream tyrosine kinase A (Trk A). However, the neuroprotective effects of 1,5-DQA were blocked by LY294002, a PI3K inhibitor, but not by PD98059, an inhibitor of mitogen-activated protein kinase kinase. Furthermore, 1,5-DQA's anti-apoptotic potential was related to the enhanced inactivating phosphorylation of glycogen synthase kinase 3beta (GSK3beta) and the modulation of expression of apoptosis-related protein Bcl-2/Bax. CONCLUSION: These results suggest that 1,5-DQA prevents Abeta(42) induced neurotoxicity through the activation of PI3K/Akt followed by the stimulation of Trk A, then the inhibition of GSK3beta as well as the modulation of Bcl-2/Bax. PMID- 22040416 TI - Amyloid beta 3-10 DNA vaccination suggests a potential new treatment for Alzheimer's disease in BALB/c mice. AB - BACKGROUND: Amyloid beta(1-42) (Abeta(42)) peptide vaccination has been proved to be effective in reducing amyloid burden in brain and improving cognitive function in Alzheimer's disease (AD) mouse models. But the phase II trial of Abeta(42) peptide vaccine was halted because of T cell-mediated meningoencephalitis. In this study, a DNA vaccine, p(Abeta(3-10))(10)-CpG, was constructed to test whether it would induce predominant T(H)2 immune response upon immunization of BALB/c mice. METHODS: BALB/c mice were vaccinated intramuscularly with p(Abeta(3 10))(10)-CpG plasmids. Abeta(42) peptide, pcDNA3.1(+) empty vector and PBS were injected to the control groups. Expression of interesting gene in injected muscle was identified by immunohistochemistry. Anti-Abeta antibody titers, isotype profiles as well as cytokines in ex vivo splenocytes culture supernatants were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: P(Abeta(3 10))(10)-CpG plasmid was expressed in muscle after injection detected by immunohistochemistry. The p(Abeta(3-10))(10)-CpG vaccine induced high titers of anti-Abeta antibodies in BALB/c mice. And isotype of the antibodies was mainly IgG1, the IgG1/IgG2a ratio for the p(Abeta(3-10))(10)-CpG group was approximately 5 times greater than that for the Abeta(42) peptide group. Ex vivo cultured splenocytes isolated from mice immunized with p(Abeta(3-10))(10)-CpG exhibited high interleukin-4 response and low interleukin-gamma (IFN-gamma) response. CONCLUSIONS: Immunization with p(Abeta(3-10))(10)-CpG vaccine primarily induces a T(H)2 type of response, thus reduces the probability of inflammation. This p(Abeta(3-10))(10)-CpG vaccine possesses the basic factors required for a safe and effective AD vaccine. PMID- 22040417 TI - Intracerebroventricular transplantation of human amniotic epithelial cells ameliorates spatial memory deficit in the doubly transgenic mice coexpressing APPswe and PS1DeltaE9-deleted genes. AB - BACKGROUND: Human amniotic epithelial cells (HAECs), which have characteristics of both embryonic and pluripotent stem cells, are therefore a candidate in cell therapy without creating legal or ethical problems. In the present study, we aimed to investigate the effects of intracerebroventricular transplantation of HAECs on doubly transgenic mice of Alzheimer's disease (AD) coexpressing presenilin-1 (PS1) and mutant Sweden amyloid precursor protein (APPswe) genes. METHODS: The offspring mice genotypes were detected using PCR identification of APPswe and PS1 gene. The doubly transgenic (TG) mice (n = 20) and wild-type (WT) mice (n = 20) were randomly divided into two groups respectively: the transplantation group treated with HAECs and the control group with phosphate buffered saline. Six radial arm water maze test was used to assess the spatial memory in the TG and WT mice. Amyloid plaques and neurofibrillary tangles were analyzed using congo red and acid-silver methenamine staining respectively. Immunofluorescence cytochemistry was used to track the survival of HAECs. Immunohistochemistry was used to determine the expression of octamer-binding protein 4 (Oct-4) and Nanog in the HAECs. High performance liquid chromatography was used to measure acetylcholine in hippocampus. The density of cholinergic neurons in basal forebrain and nerve fibers in hippocampus was measured using acetylcholinesterase staining. RESULTS: Amyloid deposition occurred in hippocampus and frontal cortex in the double TG mice aged 8 months, but not in WT mice. The results also showed that transplanted HAECs can survive for at least 8 weeks and migrate to the third ventricle without immune rejection. The graft HAECs can also express the specific marker Oct-4 and Nanog of stem cell. Compared with the control group, transplantation of HAECs can not only significantly improve the spatial memory of the TG mice, but also increase acetylcholine concentration and the number of hippocampal cholinergic neurites. CONCLUSIONS: These results demonstrate that intracerebroventricular transplantation of HAECs can improve the spatial memory of the double TG mice. The higher content of acetylcholine in hippocampus released by more survived cholinergic neurites is one of the causes of this improvement. PMID- 22040418 TI - Flunarizine inhibits sensory neuron excitability by blocking voltage-gated Na+ and Ca2+ currents in trigeminal ganglion neurons. AB - BACKGROUND: Although flunarizine has been widely used for migraine prophylaxis with clear success, the mechanisms of its actions in migraine prophylaxis are not completely understood. The aim of this study was to investigate the effects of flunarizine on tetrodotoxin-resistant Na(+) channels and high-voltage activated Ca(2+) channels of acutely isolated mouse trigeminal ganglion neurons. METHODS: Sodium currents and calcium currents in trigeminal ganglion neurons were monitored using whole-cell patch-clamp recordings. Paired Student's t test was used as appropriate to evaluate the statistical significance of differences between two group means. RESULTS: Both tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were blocked by flunarizine in a concentration-dependent manner with the concentration producing half-maximal current block values of 2.89 umol/L and 2.73 umol/L, respectively. The steady state inactivation curves of tetrodotoxin-resistant sodium currents and high voltage activated calcium currents were shifted towards more hyperpolarizing potentials after exposure to flunarizine. Furthermore, the actions of flunarizine in blocking tetrodotoxin-resistant sodium currents and high-voltage activated calcium currents were use-dependent, with effects enhanced at higher rates of channel activation. CONCLUSION: Blockades of these currents might help explain the peripheral mechanism underlying the preventive effect of flunarizine on migraine attacks. PMID- 22040419 TI - Ultrastructure and electrophysiology of astrocytes differentiated from adult adipose-derived stromal cells. AB - BACKGROUND: Adipose-derived stromal cell (ADSC) differentiation into neural cells in vitro is becoming widely studied. However, there are few reports on astrocytes following differentiation, and particularly on maturation and electrophysiology. In this study, we used various methods to determine ADSC-derived astrocyte maturity. METHODS: Chemical induction with isobutylmethylxanthine (IBMX) was used to differentiate adult ADSCs into astrocytes followed by hematoxylin-eosin (HE) staining to observe morphology and transmission electron microscopy for cellular ultrastructure assessment. Immunofluorescence was used to detect expression of neural stem cell marker nestin as well as glial markers glial fibrillary acidic protein (GFAP) and S-100. In addition, we measured membrane potentials in bis (1,3-dibarbituric acid) trimethine oxanol-labeled ADSCs and astrocytes by stimulation with a high potassium solution under an inverted fluorescence microscope. Finally, cell cycle distribution was detected by flow cytometry. RESULTS: Typical astrocyte morphology was shown by HE staining after 48-hour differentiation. Glial fibril was observed with transmission electron microscopy. GFAP and S-100 were not expressed in the control group, but were expressed within 24-hour differentiation and reached a maximum at day 14 with no change up to day 28. Nestin was weakly expressed in control cells and also reached a maximum at day 14 with the percentage of positive cells constant until day 21 followed by a decrease. Differentiated cell membrane potentials after stimulation with potassium were slightly increased, and then gradually declined over time. There was no significant membrane potential change in the control group. Flow cytometry showed that the percentage of cells in G0/G1 phase was 93% and only 5% in S phase. CONCLUSION: ADSCs were differentiated into mature astrocytes with typical characteristics including morphology, ultrastructure, marker protein expression, mature potassium channels and mitotic capacity. PMID- 22040420 TI - Etiology and prevalence of abnormal serum alanine aminotransferase levels in a general population in Northeast China. AB - BACKGROUND: Chronic liver diseases are a major burden in China. Alanine aminotransferase (ALT) can be used as an indicator of hepatocyte damage. In this study, we determined the prevalence and etiologies of elevated ALT in an adult population in Jilin, China. METHODS: A total of 4072 individuals aged between 18 and 79 years were first interviewed, and then underwent ultrasonography and blood tests. RESULTS: The prevalence of elevated ALT was 17.53%. The most noticeable risk factor for ALT elevation was non-alcoholic fatty liver disease (NAFLD) (accounting for 10.79%), metabolic syndrome (16.25%), or both (20.31%). The development of NAFLD occurred mostly in female peasants and small businessmen with increased income, age, fasting plasma glucose, body mass index, triglyceridemia, and low-density lipoprotein and decreased education level, high density lipoprotein. Elevated ALT frequently occurred in low education level, male peasants and small businessmen with increased income, body mass index and triglyceride who had NAFLD and/or metabolic syndrome. However, elevated ALT with infection of hepatitis B or C virus was not associated with metabolic disorders, but rather with gender, occupation and increased age. CONCLUSION: The results from the current study demonstrate that elevated ALT is fairly high in the Northeast population (17.53%) and that the cause of its elevation is mostly due to NAFLD and metabolic syndrome. PMID- 22040421 TI - Influenza A (H1N1) pneumonia: an analysis of 63 cases by chest CT. AB - BACKGROUND: In early April 2009, cases of human infection with 2009 pandemic influenza A (H1N1) virus were identified in Mexico. The virus then spread rapidly to other regions of the world. From October 2009, sporadic imported cases of novel influenza A (H1N1) were continuously confirmed in Suzhou. The aim of the study was to review the chest CT findings in 63 patients with laboratory confirmed novel swine-origin influenza A (H1N1) virus (S-OIV) infection. METHODS: Chest CT examinations were collected from 63 S-OIV infected patients during their hospital stay. Three experienced radiologists inspected images to qualitatively and quantitatively characterize S-OIV induced image changes. CT scores of lesion severity were calculated based on the percentage of affected area to determine severity of infectious lesions. Patients were divided into two groups based on the leukocyte counts. Lesion patterns, local distributions, and quantitative measures were investigated and compared between the two groups. RESULTS: Various degrees of bilateral multifocal lesions of ground-glass opacities were found with or without consolidations on the chest CT images. The lesions were both bronchocentric and centrilobular. Patients with elevated leukocyte counts had more extensive lesions, in terms of severity and affected area, than the patients with normal leukocyte counts. The lesion severity scores of patients in the elevated leukocyte group were significantly higher than those of the normal leukocyte group in terms of the entire lung area (P < 0.01), and upper (P < 0.05) and lower (P < 0.01) lobes as well. There were changes in the CT characteristics seen at follow-up as demonstrated by lesions absorption (P < 0.01), especially in the upper lobe of the lung (P < 0.01), but less so in the middle lobe/lingual and lower lobe of the lung (P > 0.05). CONCLUSIONS: The most common CT findings in S OIV infection patients were bilateral multifocal distributed ground-glass opacities and consolidations. The lesions were located dominantly at bronchocentric and centrilobular areas. Lung lesions were more obviously absorbed in upper lobes between two examinations. The observations and analysis from this study provide information that may be useful in image understanding and patient management for future pandemic influenza. PMID- 22040422 TI - Myocardial injury resulting from radiofrequency catheter ablation: comparison of circumferential pulmonary vein isolation and complex fractionated atrial electrograms ablation. AB - BACKGROUND: Radiofrequency catheter ablation (RFCA) necessarily produces an area of myocardial necrosis. However, the difference of the extent of myocardial injury between circumferential pulmonary vein isolation (CPVI) and complex fractionated atrial electrograms (CFAE) ablation in patients with atrial fibrillation (AF) has not been investigated before. METHODS: Twenty-nine consecutive male patients (n = 29) with either paroxysmal or persistent AF were selected for CPVI or CFAE ablation. The CPVI or CFAE ablation was performed with a three-dimensional electroanatomical mapping system (CARTO). Serum cardiac biomarkers, for example, cardiac troponin T (cTnT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase myocardial bound (CKMB) were determined by the Elecsys STATE immunoassay. Cardiac structure and function were measured with echocardiography. RESULTS: Echocardiography showed that there was no significant difference of atrioventricular structure or function parameters between the CPVI group and the CFAE ablation group. Serum cTnT showed a significant increase in the CFAE ablation group over the CPVI group at 12 and 24 hours after the procedure (P < 0.05, respectively), and then it was reduced to a normal level after 48 hours. Serum AST showed a significant increase in the CFAE ablation group over the CPVI group at post-procedure, 4 and 12 hours after the procedure (P < 0.05, respectively), and then it reached to a normal level after 24 hours. There was no significant difference in LDH, CK, or CKMB levels between the CFAE ablation group and the CPVI group at any time point (P > 0.05). CONCLUSIONS: cTnT and AST other than LDH, total CK or CKMB activity significantly increased more in the CFAE ablation group than the CPVI group. However, the difference of the serum levels of cTnT, AST between two groups was temporary. PMID- 22040423 TI - Role of plasma C-reactive protein and white blood cell count in predicting in hospital clinical events of acute type A aortic dissection. AB - BACKGROUND: A few recent studies have reported that inflammation is associated with the prognosis of acute aortic dissection (AD). There is, however, no systemic investigation regarding the role of plasma C-reactive protein (CRP) and white blood cell (WBC) levels in predicting in-hospital clinical events of acute type A AD. METHODS: The levels of high-sensitivity CRP and WBC counts were systemically determined after admission in 36 patients with acute type A AD. The variations of plasma CRP and WBC levels in different time windows (admission, 1, 2, 3, 4, 6, 8 days) in patients with acute type A AD were analyzed between patients with events and without events. RESULTS: During hospitalization, five patients died, and increased levels of CRP and WBC were found in patients died with acute type A AD compared with patients survived (P < 0.01, respectively). Medical treatment may significantly decrease inflammatory response in survived patients with acute type A AD. Additionally, patients with complication of pleural effusion showed higher CRP and WBC levels (P = 0.046, P = 0.018, respectively). Lower WBC levels were found in survived patients treated medically (P = 0.001). Moreover, mean CRP and WBC levels had positive correlations with aortic diameter (r = 0.364, P = 0.000; r = 0.333, P = 0.000, respectively) and age (r = 0.270, P = 0.000, respectively), while negative correlations with the time from onset of symptoms to hospital admission (r = -0.229, P = 0.000, r = 0.200, P = 0.002, respectively). Univariate analysis showed that age >= 65 years, CRP >= 12.05 mg/L, WBC >= 12.16 * 10(9)/L, aortic diameter >= 48 mm, pleural effusion and diastolic blood pressure >= 105 mmHg were associated with hospital mortality. While CRP >= 12.05 mg/L, WBC >= 12.16 * 10(9)/L, aortic diameter >= 48 mm were strongly associated with hospital mortality in multiple Logistic regression analysis. CONCLUSIONS: The results suggested that CRP and WBC were preferred markers for predicting the clinical events in patients with acute type A AD, especially death during hospitalization. Therefore, further study enrolling larger cohort, prospective study would be warranted. PMID- 22040424 TI - A clinical comparative study of polymerase chain reaction assay for diagnosis of pneumocystis pneumonia in non-AIDS patients. AB - BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is one of the most common and fatal infections in non-AIDS immunocompromised patients, which is difficult to diagnose by traditional morphologic methods. This study evaluated polymerase chain reaction (PCR) assays of Pneumocystis jirovecii mitochondrial large subunits ribosomal RNA in sputum and bronchioalveolar lavage fluid (BALF) for diagnosing PCP. METHODS: Sputum and BALF specimens from two groups were collected: one group (PCP group) included 20 patients definitely diagnosed of PCP by Gomori methenamine silver (GMS) stains of BALF; the other group (non-PCP group) included 40 patients. Each specimen was examined by GMS stains and PCR assays. RESULTS: GMS stains of BALF in PCP group were 100% positive (20/20), GMS stains of sputum in PCP group were 35% positive (7/20); GMS stains of BALF in non PCP group were 100% negative (40/40), GMS stains of sputum in non-PCP group were 100% negative (40/40). PCR assays of BALF in PCP group were 100% positive (20/20), PCR assays of sputum in PCP group were 100% positive (20/20); PCR assays of BALF in non-PCP group were 100% negative (40/40), PCR assays of sputum in non PCP group were 100% negative (40/40). Sensitivity and specificity of PCR assays of sputum and BALF were both 100%; positive and negative predictive values were also both 100%. CONCLUSION: The diagnostic value of PCR assays of Pneumocystis jirovecii mitochondrial large subunits ribosomal RNA on sputum and BALF for pneumocystis pneumonia are both high and equivalent. PMID- 22040425 TI - Rehabilitation of vision disorder and improved quality of life in patients with primary open angle glaucoma. AB - BACKGROUND: Primary open angle glaucoma (POAG) is a common cause of irreversible blindness. The variable etiology of POAG poses significant challenges for treatment and rehabilitation. We analyzed a large POAG patient cohort during treatment to reveal possible causes of vision disorder, assess vision-related quality of life (VRQL), and to evaluate the efficacy of rehabilitative treatments. METHODS: We analyzed the visional disturbances in 500 POAG patients (890 eyes) by regular ophthalmic examination and visual field examination using Humphrey 30 degrees perimetry. Appropriate rehabilitative treatments for POAG were prescribed based on results of clinical examination and included correction of ametropia, health education, counseling, and the fitting of typoscopes. VRQL was assessed before and after treatment by a VRQL self-assessment questionnaire. RESULTS: Scores on the VRQL self-assessment were significantly lower compared to healthy controls. The primary cause of the vision disturbances was ametropia (97.99%), and 51.61% of the ametropia eyes had not received appropriate correction. The secondary causes of visual impairment were glaucomatous neurodegeneration (26.29%), complicated cataract, or other accompanying eye diseases. The causes of the clinical low vision (44 patients) were glaucomatous neurodegeneration (32 eyes), fundus diseases (23 eyes), keratopathy (11 eyes), and other eye diseases (10 eyes). The VRQL scores of patients improved significantly after rehabilitation and the correction of ametropia (P < 0.01). Twenty-five patients with low vision were provided with typoscopes, and 21 (84%) experienced significant functional recovery, while the remaining low vision patients could see letter lines two or more levels lower (smaller) on visual charts in a near vision test. CONCLUSIONS: Vision disorders in POAG patients are common and severe. Appropriate rehabilitation, especially the correction of ametropia, can significantly improve VRQL as revealed by the self-assessment of POAG patients. PMID- 22040426 TI - Predictive value of serum cholinesterase for the prognosis of aged patients with systemic inflammatory response syndrome. AB - BACKGROUND: Some studies found that cholinesterase (ChE) can be an independent risk factor for patients with multiple organ dysfunction syndrome. To assess aged patients with systemic inflammatory response syndrome (SIRS) early and predict their prognosis, the predictive value of ChE for the prognosis of aged patients with SIRS was analyzed. METHODS: From September 2009 to September 2010, all aged patients with SIRS in the ICU of the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed if they met inclusion criteria: patients aged >= 65 years and met American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria for SIRS. Serum ChE, albumin, D-dimer, lactic acid and C-reactive protein (CRP) were measured, and the Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow Coma Scale (GCS) scores were evaluated within the first 24 hours in the ICU. Fisher's exact test was used for comparison of the primary disease between the deceased group and surviving group. For comparison of study variables between the two groups, the Student's t test or Mann-Whitney U test was used. Multivariate significance was tested with binary Logistic regression analysis. RESULTS: The clinical data of 124 aged patients with SIRS were collected and analyzed. Sixty-six patients (46 male, 20 female, mean age (78.70 +/- 8.08) years) who died were included in the deceased group and 58 patients (34 male, 24 female, mean age (76.02 +/- 6.57) years) who survived were included in the surviving group. There were no significant differences in age, gender, APACHE II score and GCS score between the deceased group and surviving group (all P > 0.05), but there were significant differences in lactic acid (P = 0.011), D-dimer (P = 0.011), albumin (P = 0.007), CRP (P = 0.008), and ChE (P < 0.0001). The correlation analysis showed that the APACHE II score and CRP were not correlated with ChE (both P < 0.05). D-dimer and albumin were correlated with ChE (Spearman's rho correlation coefficients were -0.206 and 0.324, the corresponding P values were 0.022 and < 0.0001). Multiple Logistic regression analysis showed that age, gender, lactic acid, D-dimer, albumin, CRP, APACHE II score, and GCS score were not independent risk factors for prognosis of aged patients with SIRS, but that ChE was (P < 0.0001). The receiver operating characteristic curve of ChE had an area under the curve of 0.797 (standard error = 0.04; P < 0.0001), and a ChE of 103.00 U/L was the cut-off value with sensitivity = 0.793, specificity = 0.742. CONCLUSION: Serum ChE might be a predictive marker for the prognosis of aged patients with SIRS, with low serum ChE levels indicating poor prognosis. PMID- 22040427 TI - Successfully managing a rapidly growing peritoneal dialysis program in Southern China. AB - BACKGROUND: The maximal use of the limited resource to improve peritoneal dialysis (PD) penetration and clinical outcomes is a challenge for all PD centers. In this study, we reported the experience and outcomes in successfully managing a rapidly growing PD center in Southern China. METHODS: A standard PD program with a team consisted of 6 nephrologists (3 doctors were in charge of catheter insertion and in-patients care, the other 3 doctors focused on PD patients' follow-up and education) and 11 nurses in a PD center at Sun Yat-sen University was established for PD patients follow-up in 2005. A prospective and observational study was conducted in all patients undergoing continuous ambulatory PD (CAPD) at our center from January 1, 2006 to December 31, 2009. RESULTS: The yearly number of prevalent CAPD patients was 297, 409, 547 and 695 in 2006, 2007, 2008 and 2009, respectively. The PD catheter insertion was performed by the nephrologists with open surgical procedure and 94% of catheters were patent at one year. In 841 incident CAPD patients, the survival rates at the end of 1, 2, 3 and 4 years were 94%, 87%, 83% and 76%, respectively, while cumulative technique survival rates (death-censored) were 98%, 95%, 91% and 90%, respectively. Peritonitis rate was 1/68.5 patient months. CONCLUSIONS: Better patient and technical survival rates as well as lower peritonitis episode have been achieved in our rapidly growing PD center. A standardized PD program, well trained team members of PD doctors and nurses, and continuous quality improvement of PD are important elements in managing a successful PD program. PMID- 22040428 TI - Antimicrobial resistance, genotypic characterization and pulsed-field gel electrophoresis typing of extended spectrum beta-lactamases-producing clinical Escherichia coli strains in Macao, China. AB - BACKGROUND: The rise of the production of CTX-M class extended spectrum beta lactamases (ESBLs) has been well documented in traveling countries but no data are found for Macao, an international travel city. The objectives of this study were to identify the antimicrobial resistance pattern, and determine the prevalence, genotype and clonal relationship of ESBLs in 209 clinical Escherichia coli strains from Macao, China. METHODS: Antimicrobial susceptibility test was performed to determine the resistance patterns of the isolates using the disk diffusion method with 17 antimicrobial agents. Phenotypic detection was screened and confirmed according to the Clinical and Laboratory Standards Institute. Genotypic characterization was detected by isoelectric focusing analysis, polymerase chain reaction and sequencing. The clonal relationship between the different ESBL isolates was studied by pulsed-field gel electrophoresis (PFGE). RESULTS: Imipenem and meropenem exhibited 100% susceptible among 209 strains. Overall, 82.3%, 67.3%, 52.9%, 51.2% and 51.0% of the isolates displayed resistance to ampicillin, tetracycline, ciprofloxacin, sulfamethoxazole trimethoprim and gentamycin. The prevalence rate of ESBLs was 30.1%. Antibiotic resistances were found to be significantly higher among the ESBL producing group compared to non-ESBL producing group. We detected CTX-M-14 to be the major genotypic characterization of ESBLs (76.2%). Two strains showed indistinguishable patterns by PFGE. CONCLUSIONS: The prevalence of antimicrobial resistance is alarming high in Macao. Antimicrobial resistance is significantly higher among the ESBL producing group. This study documented CTX-M-14 as the predominant ESBL type. Although indistinguishable pattern was found between two strains, it was too small to decide whether any of the investigated strains was epidemic. Our findings may be also pertinent for other geographic areas undergoing similar travel characteristics to understand the corresponding effects on bacterial populations. PMID- 22040429 TI - Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice. AB - BACKGROUND: The potential application of retinoic acid receptor activators, such as all trans-retinoic acid (ATRA), for treating various cancers have been studied both pre-clinically and clinically. Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown. We have explored the anticancer effect of ATRA in ESCC, and in this study, the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line, EC9706, in nude mice. METHODS: The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice. Reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues. RESULTS: Compared to the control group, the tumor inhibition rates in the low dose ATRA, high dose ATRA, and 5-FU groups were 83.21%, 88.32%, 91.02%, respectively. The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P < 0.05). The study also revealed that ATRA specifically down regulated VEGF and the component of the VEGF signal transduction pathway of CD31, CD34, and CD105 (component of the TGF-beta receptor) in ESCC xenograft tissues (P < 0.05). CONCLUSIONS: ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice. These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction, which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells. PMID- 22040430 TI - Bone marrow-derived mesenchymal stem cells protect rats from endotoxin-induced acute lung injury. AB - BACKGROUND: Acute lung injury (ALI) is a serious and common condition for which there are currently no specific strategies for treatment. Recent studies have suggested that bone marrow-derived multipotent mesenchymal stem cells (MSCs) may have therapeutic applications in multiple clinical disorders. We explored the biological effects of MSCs during endotoxin-induced ALI and the mechanisms involved. METHODS: MSCs were isolated from male rat bone marrow and the ALI model was induced by intravenous endotoxin injection. Female rats were sacrificed at 6 hours, 24 hours, 4 days, 1 week and 3 weeks post-injection of MSCs or saline and the lung tissue, bronchoalveolar lavage fluid, and serum were harvested for analysis. We further evaluated the survival of the rats and examined the effects of endotoxin-induced injury on the interaction between alveolar macrophages (AMs) and MSCs in ex vivo. RESULTS: There was a significant decrease in numbers of neutrophils in bronchoalveolar lavage fluid (P < 0.05), and myeloperoxidase activity in the lung (P < 0.01), and of TNF-alpha and IL-1beta in serum (P < 0.05) in the MSC treated rats at 4 days. Furthermore, MSC treated rats exhibited improved survival, lower lung injury score, higher concentration of IL-10 in the serum and a reduced hydroxyproline content, but these differences were not statistically significant. Moreover, co-cultures of MSCs and AMs had significantly reduced levels of TNF-alpha, IL-1beta and macrophage inflammatory protein (MIP)-1alpha and significantly increased levels of IL-10 (P < 0.05) in the culture supernatants. CONCLUSIONS: Treatment with intravenous injection of bone marrow-derived MSCs have beneficial effects on endotoxin-induced ALI in rats. The beneficial effect might be achieved through the engraftment of differentiated MSCs in the lungs and appears derive more from their capacity to secrete soluble factors that modulate immune responses. PMID- 22040431 TI - An improved method for rat intubation and thymectomy. AB - BACKGROUND: Thymokidney has been reported as an approach for a vascularized thymus for transplantation to induce donor specific tolerance. A completely thymectomized model which ensures that the obtained thymus is not injured has not been developed yet and it would be useful for evaluating autologous thymokidney function in rats. METHODS: Adult Sprague-Dawley male rats weighing 150 - 300 g (n = 30) underwent non-invasive intubation with the assistance of an improved self made wedge-shaped cannula made from a 2-ml plastic syringe and transillumination from the anterior tracheal area by an operation spotlight. The rats then received a thoracotomy while their breathing was supported by a small animal ventilator, and both lobes of the thymus were entirely extirpated under a 10* microscope. The postoperative survival rate of the rats was recorded, and changes in the T-cell reservoir from 9 of 30 rats within 21 days after surgery were monitored using flow cytometry. The complete thymectomy rate was confirmed by autopsy and histological examination on 21 days post-operation. RESULTS: The postoperative survival rate of rats was 100%. The exsected thymus was free of injury and the rate of complete thymectomy was 100%. CONCLUSIONS: This model has a stable survival rate and complete thymectomy is able to be achieved. The obtained thymus tissue is free of injury and can be used for transplantation. PMID- 22040432 TI - Tumor necrosis factor alpha affect hydrocortisone expression in mice adrenal cortex cells mainly through tumor necrosis factor alpha-receptor 1. AB - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is important in promoting relative adrenal insufficiency (RAI) due to systemic inflammatory response syndrome (SIRS). We identified the TNF-alpha receptor involved in the inhibition of adrenal corticotrophin (ACTH)-stimulated hydrocortisone release by studying the expression of TNF-alpha receptors in adrenal cortex Y1 cells and the effect of downregulating TNF receptors on ACTH-stimulated hydrocortisone release. METHODS: We used real-time PCR and immunocytochemistry to evaluate the expression of TNF receptors on Y1 cells. TNF-receptor 1 (TNF-R1) DNA fragments corresponding to the short hairpin RNA (shRNA)-sequences were synthesized and cloned into pcDNA(TM) 6.2-GW/EmGFP expression vector. Knockdown efficiency of TNF-R1 expression was evaluated in miRNA transfected and mock-miRNA transfected Y1 cells by quantitative real-time PCR (Q-PCR). Hydro-cortisone expression levels were determined in TNF-R1-knockdown and control Y1 cells treated with TNF-alpha and ACTH. RESULTS: Mouse adrenal cortex Y1 cells were positive for type I TNF-R1, but not type II TNF-receptor (TNF-R2). Blocking TNF-R1 expression resulted in loss of TNF-alpha-mediated inhibition of ACTH-stimulated hydrocortisone expression, suggesting a role for the TNF-R1 related signaling pathway in ACTH-stimulated hydrocortisone synthesis. CONCLUSION: The inhibitory effect of TNF-alpha on ACTH stimulated hydrocortisone synthesis was mediated via TNF-R1 in adrenal cortex. PMID- 22040433 TI - Sildenafil potentiates the proliferative effect of porcine pulmonary artery smooth muscle cells induced by serotonin in vitro. AB - BACKGROUND: Sildenafil is one of the selective phosphodiesterase 5 inhibitors that has been proven by many investigators to suppress growth factor stimulated (e.g. platelet-derived growth factor (PDGF) or epidermal growth factor (EGF)) proliferation and hypertrophy of pulmonary artery smooth muscle cells (PASMCs) via cGMP/cGKIa pathway. Serotonin promotes cell cycle progression leading to cell mitogenesis and plays a key role in the pathogenesis of pulmonary artery hypertension. The role of sildenafil in proliferation of PASMCs induced by serotonin has not been investigated so far. In this study we explored the underlying mechanism of the effect of sildenafil on serotonin induced proliferation of porcine PASMCs. METHODS: PASMCs were cells from primary cultures by the explant method from the pulmonary artery of swine and cells at passage 3 - 5 were used in this study. MTT colorimetric assay and flow cytometry analysis were used to evaluate the cell proliferation and alterations in cell cycle progression respectively. Western blotting analysis was applied to determine the expression of phosphorylated extracellular signal-regulated kinase (ERK), proliferating cell nuclear antigen (PCNA) and mitogen activated protein kinase (MAPK) phosphatase-1 (MKP-1). RESULTS: Serotonin (10 umol/L) induced the upregulation of phosphorylation of ERK1/ERK2 and PCNA, an increase in the percentage of cells in S phase and subsequent cell proliferation. Pretreatment with 1 umol/L sildenafil potentiated the phosphorylation of ERK1/ERK2, an increase in the percentage of cells in S phase and cell proliferation, compared with serotonin stimulation alone (P < 0.05). Furthermore, 30-minute pretreatment with 10 umol/L U0126, specific antagonist for ERK kinase (MEK) prevented the increase in phosphorylation of ERK1/ERK2 and abolished cell cycle progression and the proliferation of PASMCs induced by sildenafil. CONCLUSION: This study shows that sildenafil potentiated the proliferative effect of serotonin on PASMCs via phosphorylation of ERK1/ERK2. PMID- 22040434 TI - Construction of a capsule associated protein 10 gene eukaryotic expression vector for RNA interference and confirmation of biologic relevance. AB - BACKGROUND: The capsule associated protein 10 gene (cap10) is indispensible for the formation of the polysaccharide capsule, and is important in maintaining virulence of the Cryptococcus (C.) neoformans. In this study, we aimed to construct an short hairpin RNA (shRNA) expression vector targeting C. neoformans cap10 gene expression and confirm its biologic relevance. METHODS: A pair of oligonucleotides targeting the cap10 cDNA sequence was designed and synthesized. It was cloned into the plasmid psilencer4.1-CMV neo to construct an eukaryotic shRNA expression vector. The vector was transfected into C. neoformans cells using the LiAc method. The expression of cap10 was assessed by real-time fluorescence quantitative PCR. Groups of C. neoformans cells were incubated with murine macrophage-like J774A.1 cells, and the phagocytic indexes and ratios were determined by the microscopic observation method. RESULTS: The expression of cap10 in C. neoformans cells transfected with ps4.1 neo-cap10 ((175,535.00 +/- 47,004.00) copies/ul) was lower than that of cells transfected with the empty vector ((512,698.89 +/- 32,318.02) copies/ul) and mock transfected cells ((562,931.66 +/- 65,928.41) copies/ul). The average phagocytic ratio and phagocytic index of J774A.1 cells following incubation with C. neoformans were higher for cells transfected with ps4.1 neo-cap10 (0.21 +/- 0.02, (19.06 +/- 1.66)%) than for the control experimental group (0.08 +/- 0.02, (6.57 +/- 1.23)%) and the blank experimental group ((0.07 +/- 0.01), (5.89 +/- 1.07)%) (P < 0.05). CONCLUSIONS: The cap10 shRNA vector was successfully prepared and transfected into C. neoformans cells. The effect of RNA interference on the expression of the C. neoformans cap10 gene is effective, and it can induce phagocytosis of C. neoformans. PMID- 22040435 TI - Kaiyuqingre formula improves insulin secretion via regulating uncoupling protein 2 and KATP channel. AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) results from the complex association of insulin resistance and pancreatic beta-cell failure. Recent studies have shown that patients diagnosed with T2DM present with a significant decrease in beta cell function, which can be further compromised during the progression of the disease. Several mechanisms have been shown to play a role in this process such as glucotoxicity and lipotoxicity, which contribute to accelerating insulin secretion. In this regard, Chinese medicine has a certain advantage. This experiment was performed to observe the effect of a Chinese medicine named Kaiyuqingre formula (KYQRF) on beta-cell function and its mechanisms of action therein. METHODS: High glucose was used to set up a model of beta-cell function failure. At the same time, medicated serum of KYQRF with different doses were administered to the cells. Rosiglitazone was taken as a control to observe the changes in insulin secretion, ATP-sensitive K(+) channels (K(ATP) channel) and uncoupling protein-2 (UCP-2) in each group. RESULTS: KYQRF had some effects on the insulin secretion. In a low glucose environment, no effective change in insulin secretion was observed (P > 0.05). However, insulin levels increased significantly when INS-1 cells were exposed to a high glucose environment (P < 0.05). KYQRF could also enhance cell viability (P < 0.05) in an effect similar to rosiglitazone. Although KYQRF had no effect on inwardly rectifying potassium channels (Kir6.2) (P > 0.05), it could decrease the overexpression of both UCP-2 and sulfonylurea receptor 1 (P < 0.05). CONCLUSION: KYQRF can protect islet function by decreasing UCP-2 and sulfonylurea receptor 1. PMID- 22040436 TI - Chloramphenicol improved expression of recombinant cholera toxin B subunit in Escherichia coli and its adjuvanticity. AB - BACKGROUND: Cholera toxin B subunit (CTB) was shown to be a potent adjuvant for protein immunogen, especially when inoculated through mucosal route. We aimed to optimize the expression approach for CTB and thereafter to determine the adjuvant effect on DNA vaccine. METHODS: Wild type CTB coding gene was amplified and cloned into prokaryotic expression vector pET-30a, and the recombinant CTB was expressed in the presence of different concentration of chloramphenicol and isopropyl beta-D-thiogalactoside. Purified recombinant CTB was mixed with HIV-1 AE2f tat-rev-integrase-vif-nef fusion gene DNA vaccine and female BALB/c mice were vaccinated with a DNA priming-recombinant vaccinia vectored vaccine boosting regimen through intramuscular injection. Interferon gamma (IFN-gamma) enzyme linked immunospot (Elispot) assay was used to read out the specific T-cell immunity. RESULTS: Chloramphenicol was essential for the efficient expression of recombinant CTB (rCTB) in pET-30a/BL21 (DE3) system and could be optimized at the concentration of 0.625 ug/ml in the presence of chloramphenicol. The purified rCTB could bind with GM1 efficiently. INF-gamma Elispot data showed the T-cell response induced in CTB adjuvanted group ((734 +/- 240) spot forming cells/10(6) splenocytes) was higher than that induced by non-adjuvanted ((520 +/- 150) spot forming cells/10(6) splenocytes), all responses against different antigens were enhanced in parallel. CONCLUSION: CTB could be efficiently expressed in the presence of chloramphenicol and purified CTB is functional and capable of enhancing the specific T cell responses elicited by DNA vaccine, the mechanism needs to be explored in the future. PMID- 22040437 TI - Targeting glioma stem cells: enough to terminate gliomagenesis? AB - OBJECTIVE: To review the leading roles of glioma stem cells (GSCs) and their sophisticated interactions with other cells in the tissue remodeling process of gliomagenesis. DATA SOURCES: Published articles about assessing GSCs in tumor initiation, progression, and multiple interactions with other cells in the special microenvironment were selected using PubMed. The search terms were "glioma stem cells", "tumorigenesis", and "microenvironment". STUDY SELECTION: Articles regarding the tissue remodeling of GSCs in gliomagenesis were selected. RESULTS: GSCs exhibit enhanced tumor-initiating ability, could reestablish tumor, and were resistant to radiotherapy and chemotherapy. Studying the role of GSCs in gliomagenesis helps to develop targeting therapy against GSCs, which seems to be a cure for gliomas. However, sophisticated interactions between GSCs and their local microenvironment during tumor remodeling, including integrating with partially differentiated tumor cells, GSCs niche, neural stem cells (NSCs), normal glia, tumor-infiltrating lymphocytes, may obscure the leading role of GSCs during gliomagenesis, and make single targeting therapy unsuccessful. CONCLUSIONS: Understanding the biological behaviour of GSCs and their regulatory mechanisms may directly impact current efforts for more directed therapeutics against the highly aggressive gliomas. For multiple possible sources to turning into GSCs, simply eradicating the existing GSCs is not enough to be a cure for gliomas, blocking the potential sources of GSCs and ameliorating the local tumor inducing/promoting microenvironment should be a reasonable strategy. PMID- 22040438 TI - Effects of immediate and delayed mild hypothermia on endogenous antioxidant enzymes and energy metabolites following global cerebral ischemia. AB - BACKGROUND: The optimal time window for the administration of hypothermia following cerebral ischemia has been studied for decades, with disparity outcomes. In this study, the efficacy of mild brain hypothermia beginning at different time intervals on brain endogenous antioxidant enzyme and energy metabolites was investigated in a model of global cerebral ischemia. METHODS: Forty-eight male Sprague-Dawley rats were divided into a sham-operated group, a normothermia (37 degrees C - 38 degrees C) ischemic group and a mild hypothermic (31 degrees C - 32 degrees C) ischemia groups. Rats in the last group were subdivided into four groups: 240 minutes of hypothermia, 30 minutes of normothermia plus 210 minutes of hypothermia, 60 minutes of normothermia plus 180 minutes of hypothermia and 90 minutes of normothermia plus 150 minutes of hypothermia (n = 8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model for 20 minutes and mild hypothermia was applied after 20 minutes of ischemia. Brain tissue was collected following 20 minutes of cerebral ischemia and 240 minutes of reperfusion, and used to measure the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reduced glutathione (GSH) and adenosine triphosphate (ATP). RESULTS: Mild hypothermia that was started within 0 to 60 minutes delayed the consumption of SOD, GSH-Px, GSH, and ATP (P < 0.05 or P < 0.01) in ischemic tissue, as compared to a normothermic ischemia group. In contrast, mild hypothermia beginning at 90 minutes had little effect on the levels of SOD, GSH-Px, GSH, and ATP (P > 0.05). CONCLUSIONS: Postischemic mild brain hypothermia can significantly delay the consumption of endogenous antioxidant enzymes and energy metabolites, which are critical to the process of cerebral protection by mild hypothermia. These results show that mild hypothermia limits ischemic injury if started within 60 minutes, but loses its protective effects when delayed until 90 minutes following cerebral ischemia. PMID- 22040439 TI - Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1 1639A/A. AB - BACKGROUND: Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported. METHODS: Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium. RESULTS: Both cases (68 year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses. CONCLUSIONS: Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy. PMID- 22040440 TI - Acute pancreatitis in pregnancy: a 6-year single center clinical experience. AB - BACKGROUND: The acute abdomen remains a challenge for all obstetricians and physicians who take part in the care of women in pregnancy. To add substantially to our understanding of acute pancreatitis (AP) in pregnancy, in particular affirming the increased risks for mother and fetus associated with AP, we explored features of clinical manifestation and the strategy of management of this disease during pregnancy, and its effects on maternal and fetal outcomes. METHODS: A retrospective review of medical records of all pregnant patients diagnosed with AP admitted to the Department of Obstetrics and Gynecology, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University between 2005 and 2010 was performed. Information was collected from presentation, management, and outcome from medical records. RESULTS: There were 11 cases in 2010, accounting for 44% of 25 cases. Among these cases, mild AP (MAP) occurred in 15 cases (60%), while the rest cases were severe AP (SAP) (40%). The major etiology of AP in pregnancy was due to gallstone and cholecystitis. Clinical features together with elevation of the plasma concentrations of pancreatic enzymes were the cornerstones of diagnosis. Positive conservative treatment was taken in most of the cases (21 cases, 84%) with a favorable outcome. Seven cases of critically ill patients were monitored in intensive care unit, and 4 patients underwent surgical interventions. As a result, all of 25 patients had better prognosis, no maternal death was observed. There were 8 preterm labors and 2 fetal losses, accounting for the perinatal mortality of 8%. Fetal malformation was not observed. CONCLUSIONS: While a pregnant woman suffers acute abdominal pain, early diagnosis and severity assessment of AP are very important. Conservative comprehensive treatment with intensive care is recommended. Surgical intervention should be performed as late as possible. PMID- 22040441 TI - Expression of interleukin-2 in Candidal balanoposthitis and its clinical significance. AB - BACKGROUND: Candidal balanoposthitis (CB) is a common male genital infection. Autoimmune mechanisms may play an important role in the pathogenesis of CB. Interleukin-2 (IL-2) is an important molecule in cell-mediated immunity. METHODS: One hundred and one patients were diagnosed with CB using mycology culture in the dermatology and urology clinics in our hospital. Ninety-four healthy males were randomly selected as controls. We studied serum levels of IL-2 of patients with CB using ELISA and analyzed the correlations between serum IL-2 and clinical data. RESULTS: Serum IL-2 concentrations in CB patients were significantly lower than that in the control group ((7.80 +/- 4.78) vs. (15.44 +/- 7.90) ng/L; t = 2.27, P < 0.05). The incidence of CB in the low-level group was significantly higher than that in the high-level group (70% (71/101) vs. 36% (30/84), P < 0.05). Low levels of serum IL-2, comorbidity with other sexually transmitted diseases (STDs), and sexual partners with vulvovaginal candidiasis (VVC) increased the risk of CB. CONCLUSION: The pathogenesis of CB is a complex procedure that includes internal autoimmune factors. PMID- 22040442 TI - Congenital quadricuspid aortic valve: analysis of 11 surgical cases. AB - BACKGROUND: Congenital quadricuspid aortic valve is rarely seen during aortic valve replacement (AVR). The diagnosis and treatment of the disease were reported in 11 cases. METHODS: Eleven patients (nine men and two women, mean age 33.4 years) with quadricuspid aortic valve were retrospectively evaluated. Medical records, echocardiograms and surgical treatment were reviewed. RESULTS: In accordance with the Hurwitz and Roberts classification, the patients were classified as type A (n = 2), type B (n = 7), type F (n = 1) and type G (n = 1). Three patients were associated with other heart diseases, including infective endocarditis and mitral prolaps, left superior vena cava, aortic aneurysm. All had aortic regurgitation (AR) except two with aortic stenosis (AS), detected by color-flow Doppler echocardiography. The congenital quadricuspid aortic valve deformity in seven patients was diagnosed by echocardiography. All patients underwent successful aortic valve replacement. CONCLUSION: Quadricuspid aortic valve is a rare cause of aortic insufficiency, while echocardiography plays an important role in diagnosing the disease. Aortic valve replacement is the major therapy for the disease. PMID- 22040443 TI - Primary angiitis of the central nervous system: a case report. AB - Primary angiitis of the central nervous system is a rare and difficult entity. Here we represented the clinical and pathological features of a patient with little response to steroid before definite diagnosis. The 50-year-old male had a fluctuating disease course for more than 3 years. He presented visual disorders, seizure, cognitive impairment, hypersomnia, unsteady gait, dysphasia, dysphagia, and incontinence. Magnetic resonance imaging showed multiple, supratentorial and infratentorial abnormal signals, while cerebrospinal fluid and cerebral angiography were normal. Magnetic resonance spectrum showed a decrease of N acetyl-aspartate. Brain biopsy revealed nongranulomatous lymphatic vasculitis with reactive gliosis, cicatrization, demyelination and focal hemorrhages. PMID- 22040444 TI - Recurrent Fisher-Bickerstaff syndrome: report of a Chinese case. AB - Fisher-Bickerstaff syndrome (FBS) was recently proposed to help to diagnose the conditions that overlap Fisher syndrome and Bickerstaff's brainstem encephalitis, as well as the unclassified conditions that had ophthalmoplegia and ataxia with clear consciousness, flexor plantar response and preserved tendon reflexes. Recurrences are exceptional with Guillain-Barre syndrome and its variants. Here we reported a patient with diagnosis of recurrent FBS. The patient presented with recurrent drowsiness, unsteady gait, diplopia and reduced deep tendon reflexes, which met the diagnostic criteria for FBS. The interval was eight months. He was treated with intravenous immunoglobulins during each episode and got good recovery. To our knowledge, this is a relatively early report about recurrent FBS case that had central and peripheral involvement during each episode in China. PMID- 22040445 TI - Localized Castleman disease of plasma cell type in the abdomen. AB - Castleman disease is a relatively rare entity, with the hyaline-vascular type the predominant form. Although the plasma cell type is uncommon, it still comprises approximately 10% of cases of localized diseases. In addition, the abdomen is a rare site for involvement and localized Castleman disease of the plasma cell type in the abdomen is rare. The radiologic features of localized plasma cell type in the abdomen are mostly limited to case reports. In addition to the conventional imaging findings, we present some new imaging findings of localized plasma cell type in the abdomen. PMID- 22040446 TI - Contrast-enhanced ultrasound in detection and follow-up of pancreaticoduodenal artery pseudoaneurysm: a case report. AB - Pancreaticoduodenal artery pseudoaneurysm is one kind of rare splanchnic artery aneurysm. Hemorrhage from the lesion could be life-threatening. We present a case which color Doppler ultrasound and computed tomography angiography (CTA) only showed pancreatic pseudocyst on the background of chronic pancreatitis at first, but contrast-enhanced ultrasound detected blood flow in the pseudocyst and a pancreaticoduodenal artery pseudoaneurysm was worked up several days after. Finally, the pancreaticoduodenal artery pseudoaneurysm was confirmed by digital subtracted angiography. It might suggest the potential advantage of contrast enhanced ultrasound in evaluating this kind of disease in comparison of CTA. PMID- 22040447 TI - ShikaniTM Seeing Optical Stylet-aided tracheal intubation in patients with a large epiglottic cyst. AB - Large epiglottic cysts can block the glottis, leading to serious consequences. This condition presents a challenge in terms of airway management for anesthesiologists during induction of anesthesia. We report the use of a ShikaniTM Seeing Optical Stylet combined with a Macintosh laryngoscope to aid tracheal intubation in seven patients with large epiglottic cysts. Use of this technique can avoid cyst rupture and allow smooth, safe intubation. PMID- 22040448 TI - Giant epithelial splenic cyst. AB - Splenic cysts are unusual in daily surgical practice and less than 1000 cases have been reported. Primary, true or epithelial splenic cysts, are even rarer. Usually, most of the cysts are asymptomatic until of significant size, at which time they are then detected incidentally on ultrasonography or CT scan. We report a case of a 25-year-old woman with giant epithelial splenic cyst with about 3000 ml of clear-yellow fluid was collected from the cyst. The splenectomy specimen measured 205 mm * 192 mm * 137 mm and weighed 4000 g. PMID- 22040449 TI - Corresponding instability of patient and therapist process ratings in psychodynamic psychotherapies. AB - The transference relationship within the psychodynamic process was conceived of as a self-organizing system under the assumption that patient and therapist instability trajectories prove similar. Nine patients and therapists each rated their experience of the therapeutic interaction (Intrex, SASB) over the course of therapy (29 to 35 sessions). A measure of instability was calculated for these ratings across the resulting time series. The degree of synchronicity (correlation) and the correspondence of instability levels (measure of difference) were calculated for each patient-therapist dyad. Destabilization of ratings was highly synchronous and the level of destabilization corresponded highly in successful therapies. Destabilization in non-successful cases showed low synchronicity and/or therapist ratings proved more instable. The results suggest that systematically including a measure of instability and associations between patient and therapist ratings may prove fruitful in process research. PMID- 22040450 TI - Optimising the dose of oral midazolam sedation for dental procedures in children: a prospective, randomised, and controlled study. AB - BACKGROUND: Midazolam sedation poses a significant dilemma in paediatric dentistry, which is to find out the optimal dosing with minimal undesirable adverse events. In this study, we aimed to compare the effect of three doses of oral midazolam (0.5, 0.75, and 1 mg/kg) on the sedative state and cooperative behaviour of children during dental treatment. We further compared completion rates, parent satisfaction, and all adverse events. DESIGN: Ninety children aged 3-10 years were randomised to three equal groups. Groups A, B, and C received 0.5, 0.75, and 1 mg/kg of oral midazolam, respectively. Levels of sedation, cooperative behaviour, procedures completion rates, parent satisfaction, and adverse events were prospectively recorded. RESULTS: Sedation scores in B and C were higher (P < 0.001) than in A. Cooperation scores (CS) in B and C were higher (P < 0.001) than in A. Significant increase in completion rates was observed between A and C (P = 0.025). Parent satisfaction was greater in B and C (P < 0.001) compared to A. Adverse events were higher in C (P < 0.05) than in A or B. CONCLUSION: Amount of 0.75 mg/kg oral midazolam appears to be the optimal oral dose in terms of effectiveness, acceptability, and safety for dental treatments in paediatric patients, when administered by an experienced, paediatric anaesthetist. PMID- 22040451 TI - Quantitative evaluation of cryptococcal pathogenesis and antifungal drugs using a silkworm infection model with Cryptococcus neoformans. AB - AIMS: To develop an in vivo system that could quantitatively evaluate the therapeutic effects of antifungal drugs using a silkworm infection model with Cryptococcus neoformans. METHODS AND RESULTS: Silkworms reared at 37 degrees C died after an injection of viable serotype A C. neoformans fungus into the haemolymph. The serotype A C. neoformans, which is known to have higher mammal pathogenicity than the serotype D, was also more virulent against the silkworm. Furthermore, the deletion mutants of genes gpa1, pka1 and cna1, which are genes known to be necessary for the pathogenesis in mammals, showed an increase in the number of fungal cells necessary to kill half of the silkworm population (LD(50) value). Antifungal drugs, amphotericin B, flucytosine, fluconazole and ketoconazole, showed therapeutic effects in silkworms infected with C. neoformans. However, amphotericin B was not therapeutically effective when injected into the silkworm intestine, comparable to the fact that amphotericin B is not absorbed by the intestine in mammals. CONCLUSIONS: The silkworm-C. neoformans infection model is useful for evaluating the therapeutic effects of antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The silkworm infection model has various advantages for screening antifungal drug candidates. We can also elucidate the cryptococcal pathogenesis and evaluate the in vivo pharmacokinetics and toxicity of each drug. PMID- 22040452 TI - Mortality due to pandemic (H1N1) 2009 influenza in England: a comparison of the first and second waves. AB - Deaths in England attributable to pandemic (H1N1) 2009 deaths were investigated through a mandatory reporting system. The pandemic came in two waves. The second caused greater population mortality than the first (5.4 vs. 1.6 deaths per million, P<0.001). Mortality was particularly high in those with chronic neurological disease, chronic heart disease and immune suppression (450, 100, and 94 deaths per million, respectively); significantly higher than in those with chronic respiratory disease (39 per million) and those with no risk factors (2.4 per million). Greater mortality in the second wave has been observed in all previous influenza pandemics. This time, the explanation appears to be behavioural. This emphasizes the importance of maintaining public and clinical awareness of risks associated with pandemic influenza beyond the initial high profile period. PMID- 22040453 TI - Effect of constipation on serum total prostate-specific antigen levels in men. AB - OBJECTIVES: Many factors affecting serum prostate-specific antigen (PSA) levels have been described. The aim of this study was to examine the effect of constipation on serum PSA levels in men. METHODS: Serum total PSA values were measured in 136 constipated patients before and after treatment for constipation. Moreover, they were compared with 45 control patients. RESULTS: Serum total PSA values in the constipated patients before treatment were significantly higher than those in the control group (2.29 +/- 1.29 ng/mL vs 1.28 +/- 0.86 ng/mL, P < 0.0001). After the treatment of constipation, serum total PSA values in the constipated patients were still higher than those in the control group, but this difference was not statistically significant (P = 0.0871). After the treatment of constipation, prostate biopsy rates were 6.6% and 2.2% in the study and control group, respectively (P = 0.2769). No prostate cancer was found in both groups. CONCLUSIONS: Constipation increases serum PSA levels in men. The presence of constipation must be considered in patients whose PSA is examined, especially in those with PSA levels that are borderline high or in the range of 2-10 ng/mL. Constipated patients must be first treated and then re-evaluated. PMID- 22040454 TI - Chemical characterization of Klason lignin preparations from plant-based foods. AB - To analyze the accuracy of the Klason lignin method as applied for the determination of lignin contents in plant based-food products, Klason lignin preparations from curly kale, pears, whole wheat grains, and corn bran were chemically characterized. Characterization included routine ash and protein determinations and the extraction of fat/waxes as well as cutin/suberin depolymerization and extraction of the liberated monomers. Fat/wax and cutin/suberin amounts in the Klason lignin preparations were determined gravimetrically, and their compositions were analyzed by using GC-MS. Typical fat, wax, and cutin (and suberin) constituents such as saturated and unsaturated fatty acids, hydroxy and/or epoxy fatty acids, and phenolic acids were identified in all samples, whereas the detection of long-chain hydrocarbons, alcohols, and ketones, sterols, stanols, and dioic acids was dependent on the sample analyzed. Estimation of the contribution of non-lignin compounds to the Klason lignin contents reduced the noncorrected Klason lignin contents of the insoluble fibers from 28.7% (kale), 22.8% (pear), 14.8% (wheat), and 9.9% (corn) to maximum lignin contents of 6.5% (kale), 16.4% (pear), 4.9% (wheat), and 2.3% (corn). These data demonstrate that certain commonly used statements such as "cereal brans are highly lignified" need to be revised. PMID- 22040457 TI - Hospital utilization and costs for spinal cord stimulation compared with enhanced external counterpulsation for refractory angina pectoris. AB - RATIONALE, AIMS AND OBJECTIVES: The aim of this study was to compare acute hospital utilization and costs for patients with refractory angina pectoris undergoing spinal cord stimulation (SCS) versus enhanced external counterpulsation (EECP). METHOD: Seventy-three persons were included in this register study. The acute hospital utilization and costs for SCS and EECP were followed over a period from 12 months before treatment to 24 months after treatment using Patient Administrative Support in Skane for publicly organized care. RESULTS: SCS was significantly more expensive than EECP (P < 0.001). Both SCS and EECP entailed fewer days of hospitalization for coronary artery disease in the 12-month follow-up compared with the 12 months preceding treatment. Patients treated with EECP showed an association between reduced hospital admissions and an improved Canadian Cardiovascular Society classification class compared with 1 year before treatment. A significant reduction in cost was seen in both the SCS group (P = 0.018 and P = 0.001, respectively) and the EECP group (P = 0.002 and P = 0.045, respectively) during 12 and 24 months of follow-up compared with before treatment. There were no significant differences between the groups for hospitalization days or admissions, including costs, at the different follow-ups. CONCLUSIONS: Cost-effective treatment modalities such as SCS and EECP are valuable additions to medical and revascularization therapy in patients with refractory angina pectoris. Pre-existing conditions and the patient's preferences should be taken in consideration when clinicians choose between treatments for this group of patients. PMID- 22040455 TI - Differential genetic interactions between Sgs1, DNA-damage checkpoint components and DNA repair factors in the maintenance of chromosome stability. AB - BACKGROUND: Genome instability is associated with human cancers and chromosome breakage syndromes, including Bloom's syndrome, caused by inactivation of BLM helicase. Numerous mutations that lead to genome instability are known, yet how they interact genetically is poorly understood. RESULTS: We show that spontaneous translocations that arise by nonallelic homologous recombination in DNA-damage checkpoint-defective yeast lacking the BLM-related Sgs1 helicase (sgs1Delta mec3Delta) are inhibited if cells lack Mec1/ATR kinase. Tel1/ATM, in contrast, acts as a suppressor independently of Mec3 and Sgs1. Translocations are also inhibited in cells lacking Dun1 kinase, but not in cells defective in a parallel checkpoint branch defined by Chk1 kinase. While we had previously shown that RAD51 deletion did not inhibit translocation formation, RAD59 deletion led to inhibition comparable to the rad52Delta mutation. A candidate screen of other DNA metabolic factors identified Exo1 as a strong suppressor of chromosomal rearrangements in the sgs1Delta mutant, becoming even more important for chromosomal stability upon MEC3 deletion. We determined that the C-terminal third of Exo1, harboring mismatch repair protein binding sites and phosphorylation sites, is dispensable for Exo1's roles in chromosomal rearrangement suppression, mutation avoidance and resistance to DNA-damaging agents. CONCLUSIONS: Our findings suggest that translocations between related genes can form by Rad59 dependent, Rad51-independent homologous recombination, which is independently suppressed by Sgs1, Tel1, Mec3 and Exo1 but promoted by Dun1 and the telomerase inhibitor Mec1. We propose a model for the functional interaction between mitotic recombination and the DNA-damage checkpoint in the suppression of chromosomal rearrangements in sgs1Delta cells. PMID- 22040458 TI - The species-specific mode of action of the antimicrobial peptide subtilosin against Listeria monocytogenes Scott A. AB - AIMS: To elucidate the molecular mechanism of action of the antimicrobial peptide subtilosin against the foodborne pathogen Listeria monocytogenes Scott A. METHODS AND RESULTS: Subtilosin was purified from a culture of Bacillus amyloliquefaciens. The minimal inhibitory concentration of subtilosin against L. monocytogenes Scott A was determined by broth microdilution method. The effect of subtilosin on the transmembrane electrical potential (DeltaPsi) and pH gradient (DeltapH), and its ability to induce efflux of intracellular ATP, was investigated. Subtilosin fully inhibited L. monocytogenes growth at a concentration of 19 MUg ml(-1) . Subtilosin caused a partial depletion of the DeltaPsi and had a similar minor effect on the DeltapH. There was no significant efflux of intracellular ATP. CONCLUSION: Subtilosin likely acts upon L. monocytogenes Scott A by perturbing the lipid bilayer of the cellular membrane and causing intracellular damage, leading to eventual cell death. Subtilosin's mode of action against L. monocytogenes Scott A differs from the one previously described for another human pathogen, Gardnerella vaginalis. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the specific mode of action of subtilosin against L. monocytogenes and the first report of a bacteriocin with a species-specific mode of action. PMID- 22040459 TI - Rapid typing of foot-and-mouth disease serotype Asia 1 by reverse transcription loop-mediated isothermal amplification. AB - A reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay was rapidly used to detect serotype Asia 1 of foot-and-mouth disease virus (FMDV) within 45 min at 61 degrees C. All FMDV serotype Asia 1 reference strains were positive by RT-LAMP, while other viruses such as FMDV serotypes O, C, A and classical swine fever virus, swine vesicular disease virus, porcine reproductive and respiratory syndrome virus and Japanese encephalitis virus remained negative. Furthermore, FMDV sreotype Asia 1 positive samples were able to detect by RT-LAMP assay. This RT-LAMP assay may be suitable particularly for diagnosis of FMDV serotype Asia 1 infection in field stations. PMID- 22040460 TI - Leaf extracts from Nitraria retusa promote cell population growth of human cancer cells by inducing apoptosis. AB - BACKGROUND: In this report the phytochemical profile of Nitraria. Retusa (N. Retusa) leaf extracts were identified and their ability to induce apoptosis in human chronic myelogenous erythroleukaemia (K562) was evaluated. METHODS: Apoptosis of the human chronic myelogenous erythroleukaemia (K562) was evidenced by investigating DNA fragmentation, PARP cleavage and caspases 3 and 8 inducing activities, in the presence of N. retusa extracts. RESULTS: Our study revealed that the tested extracts from N. Retusa contain many useful bioactive compounds. They induced in a time-dependent manner the apoptosis the tested cancerous our cell line. This result was confirmed by ladder DNA fragmentation profile and PARP cleavage, as well as a release in caspase-3 and caspase-8 level. CONCLUSION: Our results indicate that the tested compounds have a significant antiproliferative effect which may be due to their involvement in the induction of the extrinsic apoptosic pathway. PMID- 22040462 TI - Plasmonic photosensitization of a wide band gap semiconductor: converting plasmons to charge carriers. AB - A fruitful paradigm in the development of low-cost and efficient photovoltaics is to dope or otherwise photosensitize wide band gap semiconductors in order to improve their light harvesting ability for light with sub-band-gap photon energies.(1-8) Here, we report significant photosensitization of TiO2 due to the direct injection by quantum tunneling of hot electrons produced in the decay of localized surface-plasmon polaritons excited in gold nanoparticles (AuNPs) embedded in the semiconductor (TiO2). Surface plasmon decay produces electron hole pairs in the gold.(9-15) We propose that a significant fraction of these electrons tunnel into the semiconductor's conduction band resulting in a significant electron current in the TiO2 even when the device is illuminated with light with photon energies well below the semiconductor's band gap. Devices fabricated with (nonpercolating) multilayers of AuNPs in a TiO2 film produced over 1000-fold increase in photoconductance when illuminated at 600 nm over what TiO2 films devoid of AuNPs produced. The overall current resulting from illumination with visible light is ~50% of the device current measured with UV (homega>Eg band gap) illumination. The above observations suggest that plasmonic nanostructures (which can be fabricated with absorption properties that cover the full solar spectrum) can function as a viable alternative to organic photosensitizers for photovoltaic and photodetection applications. PMID- 22040461 TI - Effect of L-carnitine on the hepatic transcript profile in piglets as animal model. AB - BACKGROUND: Carnitine has attracted scientific interest due to several health related effects, like protection against neurodegeneration, mitochondrial decay, and oxidative stress as well as improvement of glucose tolerance and insulin sensitivity. The mechanisms underlying most of the health-related effects of carnitine are largely unknown. METHODS: To gain insight into mechanisms through which carnitine exerts its beneficial metabolic effects, we fed piglets either a control or a carnitine supplemented diet, and analysed the transcriptome in the liver. RESULTS: Transcript profiling revealed 563 genes to be differentially expressed in liver by carnitine supplementation. Clustering analysis of the identified genes revealed that most of the top-ranked annotation term clusters were dealing with metabolic processes. Representative genes of these clusters which were significantly up-regulated by carnitine were involved in cellular fatty acid uptake, fatty acid activation, fatty acid beta-oxidation, glucose uptake, and glycolysis. In contrast, genes involved in gluconeogenesis were down regulated by carnitine. Moreover, clustering analysis identified genes involved in the insulin signaling cascade to be significantly associated with carnitine supplementation. Furthermore, clustering analysis revealed that biological processes dealing with posttranscriptional RNA processing were significantly associated with carnitine supplementation. CONCLUSION: The data suggest that carnitine supplementation has beneficial effects on lipid and glucose homeostasis by inducing genes involved in fatty acid catabolism and glycolysis and repressing genes involved in gluconeogenesis. PMID- 22040463 TI - Preventive chemotherapy in human helminthiasis: theoretical and operational aspects. AB - Preventive chemotherapy (PC), the large-scale distribution of anthelminthic drugs to population groups at risk, is the core intervention recommended by the WHO for reducing morbidity and transmission of the four main helminth infections, namely lymphatic filariasis, onchocerciasis, schistosomiasis and soil-transmitted helminthiasis. The strategy is widely implemented worldwide but its general theoretical foundations have not been described so far in a comprehensive and cohesive manner. Starting from the information available on the biological and epidemiological characteristics of helminth infections, as well as from the experience generated by disease control and elimination interventions across the world, we extrapolate the fundamentals and synthesise the principles that regulate PC and justify its implementation as a sound and essential public health intervention. The outline of the theoretical aspects of PC contributes to a thorough understanding of the different facets of this strategy and helps comprehend opportunities and limits of control and elimination interventions directed against helminth infections. PMID- 22040464 TI - Autism in Glasgow: cumulative incidence and the effects of referral age, deprivation and geographical location. AB - BACKGROUND: Referrals to the Greater Glasgow Community Autism Team (CAT) made before the child's sixth birthday were analysed to obtain an estimation of the proportion of children in Greater Glasgow with childhood autism and investigate whether there were any variations in diagnosis rates, or in age at referral and diagnosis, depending on deprivation or geographical location. METHODS: An analysis was made of the database recording referrals to Greater Glasgow CAT, between 2004 and 2007 inclusive, of children referred by age 6 years, comprising 584 cases. Cumulative incidence was calculated for childhood autism. Ages at referral and diagnosis were also analysed. RESULTS: For this subset of children, there were 246 diagnosed cases of childhood autism, a cumulative incidence from 2004 until 2007 of 11.1 per year per 10,000 children aged 0-6 years. Of children with an eventual diagnosis of autism by age 6, 72% were referred by the age of 4 years. Deprivation was found to have an association with referral and diagnostic rates, with higher rates seen in the most deprived. There was geographical variation in the cumulative incidence of autism. CONCLUSION: Given that the populations were not known to differ in any manner that would lead to a true variation, the geographical variation in the cumulative incidence of autism in children up to 6 years in Greater Glasgow observed in this study is likely to represent differences in the care pathway between areas. Such differences may also explain the observed association with deprivation. Reasons for the variation are being explored. PMID- 22040465 TI - Enteral n-3 fatty acids and micronutrients enhance percentage of positive neutrophil and lymphocyte adhesion molecules: a potential mediator of pressure ulcer healing in critically ill patients. AB - n-3 Fatty acids are recognised as influencing both wound healing and immunity. We assessed the impact of a fish oil- and micronutrient-enriched formula (study formula) on the healing of pressure ulcers and on immune function in critically ill patients in an intensive care unit. A total of forty patients with pressure ulcers and receiving nutritional support were enrolled (intervention group, n 20, received study formula; and a control group, n 20, received an isoenergetic formula). Total and differential leucocyte count and percentage of adhesion molecule positive granulocyte and lymphocyte cells (CD11a, CD11b, CD18 and CD49b) were measured on days 0, 7 and 14. Percentage of positive lymphocytes for CD54, CD49b, CD49d and CD8 were also measured on days 0, 7 and 14. The state of pressure ulcers was assessed by using the pressure ulcer scale for healing tool score on days 7, 14 and 28 of treatment. No between-group differences in patient demographics, anthropometry or diagnostic class were observed. Patients who received the study formula showed significant increases in the percentage of positive CD18 and CD11a lymphocytes and of CD49b granulocytes as compared to controls (P < 0.05). While the severity of pressure ulcers was not significantly different between the two groups on admission, severity increased significantly over time for the control group (P < 0.05), but not for the study group. The present study suggests that a fish oil- and micronutrient-enriched formula may prevent worsening of pressure ulcers and that this effect may be mediated by an effect on adhesion molecule expression. PMID- 22040466 TI - Transient psychosis due to painless thyroiditis in a patient with anxiety disorder: a case report. AB - INTRODUCTION: There are few reports on thyrotoxic psychosis caused by diseases other than Graves' disease or toxic nodular goiter. CASE PRESENTATION: A 64-year old Japanese woman was treated for anxiety disorder in our clinic for 10 years. She had five episodes of transient psychosis during the first five years. When she developed psychosis without neck pain 10 years after her first visit, a laboratory reexamination revealed that she had subclinical hyperthyroidism, and tested positive for antithyroid autoantibodies, negative for thyroid stimulating hormone receptor antibody and had decreased radioactive iodine uptake. She was diagnosed as having painless thyroiditis. The hyperthyroidism disappeared within a month, and the psychosis lasted for three months. CONCLUSION: To the best of our knowledge, this is the first report of psychosis due to painless thyroiditis induced hyperthyroidism. Physical symptoms of painless thyroiditis are often so mild that careful differential diagnosis is necessary in the cases of transient psychosis. PMID- 22040467 TI - Prospective observation of a new bioactive luting cement: 2-year follow-up. AB - PURPOSE: A pilot study was conducted to determine the 2-year clinical performance of a new bioactive dental cement (Ceramir C&B, formerly XeraCem) for permanent cementation. MATERIALS AND METHODS: The cement used in this study is a new formulation class, a hybrid material comprising calcium aluminate and glass ionomer. Thirty-eight crowns and fixed partial denture (FPD) abutments were cemented in 17 patients. Thirty-one of the abutment teeth were vital, 7 nonvital. Six reconstructions were FPDs comprising 14 abutment teeth (12 vital/2 nonvital). A two-unit fixed splint was also included. Preparation parameters and cement characteristics (dispensing, working time, seating characteristics, ease of cement removal) were recorded. Baseline and postcementation data were recorded for marginal integrity, marginal discoloration, secondary caries, retention, and gingival inflammation. Tooth sensitivity was assessed at pre- and postcementation time points using categorical and visual analogue scale (VAS) assessment measures. RESULTS: Mixing of the cement was reported as "easy." Clinical working time for this cement was deemed acceptable. Assessment of seating characteristics indicated all restorations were seated completely after cementation. Cement removal was determined to be "easy." Fifteen of 17 subjects were available for 1 year recall examination; 13 patients were available for the 2-year recall examination. Restorations at 2-year recall examination included 17 single-unit, full-coverage crown restorations, four 3-unit FPDs comprising 8 abutments, and one 2-unit splint. No retentive failures or sensitivity were recorded at 2-year recall. Marginal integrities of all restorations/abutments at 2 years were rated in the "alpha" category. Average VAS score for tooth sensitivity decreased from 7.63 mm at baseline to 0.44 mm at 6-month recall, 0.20 mm at 1-year recall, and 0.00 mm at 2-year recall. The average gingival index score for gingival inflammation decreased from 0.56 at baseline to 0.11 at 6-month recall, then 0.16 at 1-year recall, and 0.21 at 2-year recall. CONCLUSIONS: Two-year recall data yielded no loss of retention, no secondary caries, no marginal discolorations, and no subjective sensitivity. All restorations rated "alpha" for marginal integrity at the 2-year recall. After periodic recalls up to 2 years, the new bioactive cement tested thus far has performed favorably as a luting agent for permanent cementation. PMID- 22040468 TI - Humoral immunity to AAV-6, 8, and 9 in normal and dystrophic dogs. AB - Adeno-associated virus (AAV)-6, 8, and 9 are promising gene-delivery vectors for testing novel Duchenne muscular dystrophy gene therapy in the canine model. Humoral immunity greatly influences in vivo AAV transduction. However, neutralizing antibodies to AAV-6, 8, and 9 have not been systemically examined in normal and dystrophic dogs. To gain information on the seroprevalence of antibodies to AAV-6, 8, and 9, we measured neutralizing antibody titers using an in vitro transduction inhibition assay. We examined 72 naive serum samples and 26 serum samples obtained from dogs that had received AAV gene transfer. Our data demonstrated that AAV-6 neutralizing antibody was the most prevalent antibody in dogs irrespective of age, gender, disease status (dystrophic or not), and prior parvovirus vaccination history. Surprisingly, high-level anti-AAV-6 antibody was detected at birth in newborn puppies. Further, a robust antibody response was induced in affected, but not normal newborn dogs following systemic AAV gene transfer. Taken together, our data have provided an important baseline on the seroprevalence of AAV-6, 8, and 9 neutralizing antibodies in normal and Duchenne muscular dystrophy dogs. These results will help guide translational AAV gene therapy studies in dog models of muscular dystrophy. PMID- 22040470 TI - Aims and scope. PMID- 22040469 TI - Introducing the veterinary quarterly. PMID- 22040471 TI - Food-borne parasitic infections - old stories and new facts. AB - Summary A review is presented of food-borne parasitic infections. Parasitic infections with public health hazards both from conventional slaughter animals and from seafood (fish and shellfis) are discussed. The former category includes cysticercosis, echinococcosis, and trichinosis, the latter category covers various trematode, cestode, nematode, and possibly also protozoan infections. Examples of trematode infections are heterophyidiasis, transmitted to man by marine fish, and Paragonimus spp parasites, transmitted by crustaceans. Cestode infections include diphyllobothriasis transmitted by both fresh waterfish and fish from brackish waters. Special attention is drawn to the condition known as sparganosis. Of the nematode infections, the eosinophilic granulomatous enteritis due to the genera A nisakis, Phocanema, and Contracaecum, transmitted to man by either marine fish or crustaceans, is mentioned. Two other nematode infections. Angiostrongylus cantonensis and Capillaria philippinensis, can also be transmitted to man by marine fish. Free living amoebae (a.o. Naegleria) may be transmitted to man via shellfish as vehicles. Apart from a possible direct effect of these parasites, chemical alterations in seafood resulting from the presence of parasites may also be deleterious to the consumer. Special attention is drawn to a newly developed serological detection method, the enzyme linked immunosorbent assay, which makes detection of infection possible not only at the slaughterhouse but also at the farm or in large herds. Strategies to control parasitic infections both in conventional slaughter animals and in seafood are discussed. PMID- 22040472 TI - Blood parasites of sheep in the Netherlands. I. Anaplasma mesaeterum sp.n. (Rickettsiales, Anaplasmataceae). AB - Summary On two occasions an anaplasm was isolated from sheep on the Dutch island of Ameland. The organism proved to be highly pathogenic for splenectomised sheep; a non-splenectomised animal recovered spontaneously after the packed cell volume had decreased by 40%. Treatment with oxytetracycline was effective. Its pathogenicity for goats appeared to be low, and the organism was apparently not infective to splenectomised cattle. This anaplasm differs from Anaplasma ovis in that less than 30% of the organisms are marginally situated in the red cell, as against over 70% in A. ovis; cross-immunity with A. ovis was incomplete and the latter appeared to be far more pathogenic to goats than the Dutch anaplasm, for which the name Anaplasma mesaeterum sp.n. is proposed. Its ultrastructure is similar to that of A. marginale and A. ovis. The vector is either Ixodes ricinus or Haemaphysalis punctata. Its practical importance remains to be ascertained. PMID- 22040473 TI - The control of lymphoid leukosis in a flock White Plymouth Rock chickens. AB - Summary Lymphoid leukosis (LL) was successfully controlled in a commercial basic breeding line of White Plymouth Rock chickens. The control method has been developed for breeder flocks and consists of three elements: - In the flock under study, homogenates of embryos from all eggs collected during a number of I4-day periods are tested for the presence of LL viruses. - Only eggs from hens that have been shown not to shed virus in their eggs are used for the production of progeny. The offspring are reared in isolation during the first two months of life, at which time the age-related resistance against tumour formation by LL viruses appears to be sufficiently developed. - The chickens are subsequently inoculated intramuscularly with LL viruses of subgroups A and B transferred to a conventional chicken house. The vaccination raises a solid immunity to horizontal LL virus exposure and, due to the age-related resistance, tumour formation does not follow. No excretion of LL viruses could be detected in three generations of White Plymouth Rock chickens to which the three elements of the control procedure were applied. Clinical disease was not observed in any of the chickens under notice. PMID- 22040474 TI - Influence of ante- and peri-mortem factors on biochemical and physical characteristics of turkey breast muscle. AB - Summary The course of post-mortem breakdown of glycogen and ATP in turkey pectoralis major muscle was markedly influenced by several ante- and peri-mortem variables. Application of a proper stunning procedure was highly effective in preventing peri- and post-mortem muscle stress reactions. The physiological level of glycogen and ATP was not significantly affected by road transportation covering 260 km. Birds which rested for 24 hrs following transportation had lower glycogen and ATP levels at the moment of slaughter than non-rested birds. According to the changes in the rate and extent of post-mortem biochemical reactions, several meat characteristics such as water-holding capacity, colour, and tenderness were significantly changed. Furthermore, the results also indicate that turkey breast muscle is susceptible to a PSE-like condition as described in pork. PMID- 22040475 TI - Differences in mastitis susceptibility between Holstein Friesian, Dutch Friesian and Dutch Red and White cows. AB - Summary On an experimental farm 3 dairy breeds were compared with regard to mastitis by various parameters. Higher cell counts and more udder infections were present in the Dutch Red and White (DRW) in comparison with the Holstein Friesian (HF) and the Dutch Friesian (DF). Within the HF breed a negative correlation between cell count and production was established and also in this breed, a negative correlation between maximum rate of milk flow and cell count. There is no evidence that higher procuction and easier milking are connected with more mastitis. On the contrary, within the breeds an opposite trend appeared. Selection against mastitis does not conflict with selection for production and ease of milking. An addition trial revealed that sampling after too quick preparation of the cows before milking resulted in much higher cell counts in quarter samples. Cows which were selected for drying off with antibiotics recovered from their infection but these more susceptible animals maintained a higher cell count to a certain extent. PMID- 22040476 TI - Serum chloramphenicol levels and the intramuscular bioavailability of several parenteral formulations of chloramphenicol in ruminants. AB - Summary Serum chloramphenicol concentrations were determined by microbiological and chemical assay methods in cows, ewes, and goats treated parenterally with seven different veterinary parenteral chloramphenicol products, including the water soluble sodium succinate ester of chloramphenicol and solutions of 20%, 25% and 50% of chloramphenicol base in various organic solvents. Serum drug concentrations were analyzed for the effect of product formulation differences, dosage, whether the drug was administered i.m. at a single body site or to two sites, and the method of assay, on the absorption from the injection site, peak drug levels, and the persistence in serum of effective concentrations of the drug i.e. 5 to 10 ug / ml. Although differences were observed among the 6 products containing chloramphenicol base in respect to absorption rate and peak serum drug levels, and although these differences significantly influenced the persistence of microbiologically-active serum drug concentrations at the level of >= 10 MUg / ml, they did not at the level of >= 5 MUg / ml. In the animal species examined, injections given at 2 sites appeared to influence the duration of predetermined serum drug levels more than the differences among the products in respect of the absorption and elimination rates from serum, the peak serum concentrations, and the dose. The shapes of the concentration-to-time curves in cows and ewes injected with the same dose of a given product were essentially the same, but they were different in goats. Serum chloramphenicol concentrations measured chemically after treatment with chloramphenicol base were 20% to 46% higher than those measured microbiologically. For 60 minutes after the sodium succinate ester had been administered i.v. and i.m. to ewes, the chemically determined chloramphenicol levels were more than twice as high as the respective concentrations determined by microbiological assay, but thereafter, the magnitude of those differences was not greater than observed after treatment with chloramphenicol base. Intramuscular bioavailability of the products containing chloramphenicol base injected at 2 sites was rather poor (51% to 80.5%ofthe dose) and even lower values were calculated after injection at a single site. Results are briefly discussed of the effect of dosage form on the persistence of microbiologically effective serum drug levels. A dose of at least 50 mg / kg to be administered i.m. at two sites are essential prerequisits for chloramphenicol therapy in ruminants. PMID- 22040477 TI - ELISA for the serology of FIP virus. AB - Summary An enzyme linked immunosorbent assay (ELISA) for feline infectious peritonitis (FIP) virus serology is described. The assay is analogous to a previously developed indirect heterologous immunofluorescence test (IFT) in which transmissible gastroenteritis (TGE) viral antigen was used. Comparative testing of selected feline sera in both assays resulted in corresponding titers, which justifies the conclusion that the ELISA is a reliable test for the serology of FIP virus. PMID- 22040480 TI - Investigation into the use of complementary and alternative medicine and affecting factors in Turkish asthmatic patients. AB - AIMS: The purpose of this study was to examine the frequency of complementary and alternative medicine usage in asthmatic patients living in the west of Turkey, the most frequently used complementary and alternative medicine methods and socio demographic factors affecting this and factors related to the disease. BACKGROUND: While the rate of complementary and alternative medicine usage in asthmatic patients and the reasons for using it vary, practices specific to different countries and regions are of interest. Differing cultural and social factors even in geographically similar regions can affect the type of complementary and alternative medicine used. METHODS: Two hundred asthmatic patients registered in the asthma outpatient clinic of a large hospital in Turkey and who had undergone pulmonary function tests within the previous six months were included in this study, which was planned according to a descriptive design. The patients filled out a questionnaire on their demographic characteristics and complementary and alternative medicine usage. RESULTS: The proportion of patients who reported using one or more of the complementary and alternative medicine methods was 63.0%. Of these patients, 61.9% were using plants and herbal treatments, 53.2% were doing exercises and 36.5% said that they prayed. The objectives of their use of complementary and alternative medicine were to reduce asthma-related complaints (58%) and to feel better (37.8%). The proportion of people experiencing adverse effects was 3.3% (n = 4). Factors motivating asthmatic patients to use complementary and alternative medicine were the existence of comorbid diseases and a long period since diagnosis (p < 0.05). No statistically significant difference was found between the use of complementary and alternative medicine and the severity of the disease, pulmonary function test parameters, the number of asthma attacks or hospitalisations because of asthma within the last year (p > 0.05). RELEVANCE TO CLINICAL PRACTICE: Understanding by nurses of the causes and patterns of the use of complementary and alternative medicine in asthmatic patients helps them in directing patient care and patient safety. Nurses should conduct comprehensive diagnostics in the light of complementary and alternative medicine use, and they should be aware of the potential risks. PMID- 22040481 TI - Weak and strong publics: drawing on Nancy Fraser to explore parental participation in neonatal networks. AB - AIMS: We draw on the work of Nancy Fraser, and in particular her concepts of weak and strong publics, to analyze the process of parental involvement in managed neonatal network boards. BACKGROUND: Public involvement has moved beyond the individual level to include greater involvement of both patients and the public in governance. However, there is relatively little literature that explores the nature and outcomes of long-term patient involvement initiatives or has attempted to theorize, particularly at the level of corporate decision making, the process of patient and public involvement. METHODS: A repeated survey of all neonatal network managers in England was carried out in 2006-07 to capture developments and changes in parental representation over this time period. This elicited information about the current status of parent representation on neonatal network boards. Four networks were also selected as case studies. This involved interviews with key members of each network board, interviews with parent representatives, observation of meetings and access to board minutes. RESULTS: Data collected show that a wide range of approaches to involving parents has been adopted. These range from decisions not to involve parents at this level to relatively well-developed systems designed to link parent representatives on network boards to parents in neonatal units. CONCLUSION: Despite these variations, we suggest that parental participation within neonatal services remains an example of a weak public because the parent representatives had limited participation with little influence on decision making. PMID- 22040482 TI - Recent trends in the epidemiology of non-typhoidal Salmonella in Israel, 1999 2009. AB - The aim of the present study was to assess the recent trends in the epidemiology of non-typhoid Salmonella in Israel using a sentinel laboratory-based surveillance network. Between 1999 and 2009, 8758 Salmonella stool isolates were reported by five sentinel laboratories. There was a significant decrease in the incidence rate of Salmonella isolates from 70.5/100,000 in 1999 to 21.6/100,000 in 2005 followed by a slight increase to 30.3/100,000 in 2009. Of all Salmonella, 64.3% were isolated from children in the 0-4 years age group. Up to 2008, S. Enteritidis was the most prevalent serotype and in 2009 S. Infantis emerged as the most common Salmonella serotype. The decrease in the incidence of S. Enteritidis and S. Typhimurium and increase in S. Infantis among humans were associated with a similar trend among breeding flocks, which followed significant preventive interventions conducted against S. Enteritidis and S. Typhimurium infections in poultry. Tight surveillance and education of food handlers and consumers should be enhanced to reduce the foodborne transmission of Salmonella in Israel. PMID- 22040483 TI - Auto-versus allo-transplantation of the liver for end-stage alveolar echinococcosis? PMID- 22040484 TI - Hydatid cyst/cystic echinococcosis: anatomical and surgical nomenclature and method to quantify the cyst content solidification. AB - The terminology related to the hydatid cyst is sometimes inappropriate and wrong designations are used, based on incorrect concepts. "Hydatid cyst" is the larval form of the tapeworms of the genus Echinococcus granulosus, a parasite found in the small intestine of carnivores. The disease, called cystic echinococcosis, is among the most neglected parasitic diseases despite the development of new drugs and other treatment modalities. Although all of us know the vital cycle of the parasite and the different aspects of the disease, the designations around the parasite, its evolution and some therapeutic procedures are not uniform. It would be useful, for all of us, to use the same nomenclature and it is absolutely necessary that the nomenclature is correct and universally accepted. In this paper I remember the correct terms related to all aspects of the hydatid cyst's nomenclature, including especially the anatomical and surgical terminology, as well as the criteria to define the cyst inactivity and the way to know when the cyst range the inactive stage after therapy. PMID- 22040485 TI - Ex vivo liver resection followed by autotransplantation for end-stage hepatic alveolar echinococcosis. AB - BACKGROUND: For patients with end-stage hepatic alveolar echinococcosis (AE), in vivo resection of the involved parts of the liver is usually very difficult, therefore, allogenic liver transplantation is indicated. However, we hypothesize that for selected patents, ex vivo liver resection for thorough elimination of the involved tissues and liver autotransplantation may offer a chance for clinical cure. METHODS: We presented a 24-year-old women with a giant hepatic AE lesion who was treated with hepatectomy, ex vivo resection of the involved tissue and hepatic autotransplantation. The patient had moderate jaundice and advanced hepatic AE lesion which involved segments I, IV, V, VI, VII, VIII and retrohepatic inferior vena cava. The lateral segments (II and III) of the left liver remained normal with over 1000 ml in its volume. No extrahepatic metastases (such as to the lung or brain) could be found. As the first step of treatment, X ray guided percutaneous transhepatic cholangiodrainage (PTCD) was performed twice for bile drainage in segment III and II separately until her serum total bilirubin decreased gradually from 236 to 88 umol/L. Total liver resection was then performed, followed by extended right hepatic trisegmentectomy and the entire retrohepatic vena cava was surgically removed en bloc while her hemodynamics parameters were stable. Neither veino-veinous bypass nor temporary intracorporeal cavo-caval or porto-caval shunt was used during the 5.7-hour anhepatic phase. The remained AE-free lateral segments of the left liver were re implanted in situ. The left hepatic vein was directly anastomosed end-to-end to the suprahepatic inferior vena cava due to the lack of the retrohepatic inferior vena cava with AE total infiltration. Because compensatory retroperitoneal porto caval collateral circulation developed, we enclosed remained infrahepatic inferior vena cava at renal vein level without any haemodynamics problems. RESULTS: During a 60-day following-up after operation, the patient had a good recovery except for a mildly elevated serum total bilirubin. CONCLUSIONS: As a radical approach, ex vivo liver resection and liver autotransplantation in a case has shown a optimal potential for treatment of the end-stage hepatic AE. Strict compliance with its indications, evaluation of vessels of patients pre operatively, and precise surgical techniques are the keys to improve the prognosis of patients. PMID- 22040486 TI - Suppression of acute rejective response following orthotopic liver transplantation in experimental rats infected with Echinococcus multilocularis. AB - BACKGROUND: Hepatic alveolar echinococcosis (AE) is a parasitic disease in humans and caused by the Echinococcus multilocularis (Em). Orthotopic liver transplantation (OLT) may be the only effective treatment for end-stage hepatic AE. However, in some AE patients, extrahepatic Em can not be completely eliminated after OLT. We aimed to study whether the immunological changes caused by Em evasion may influence the rejective response. METHODS: Rat modles of AE were established by injecting the Em suspension into abdomen of Brown Norway (BN) rats. Three months later, in the experimental group, the liver was transplanted from Lewis (LEW) rats to Em-infected BN rats. In the control group, transplantation was from LEW rats to healthy BN rats. Liver tissue and peripheral blood (PB) samples were collected on days 1, 3, 5, and 7 after OLT. Liver tissue was analyzed after hematoxylin and eosin (H&E) staining; numbers of CD4, CD8, and CD28 on peripheral blood cells were detected by flow cytometry; and expression of the chemokine fractalkine (Fkn) was detected by reverse transcription PCR (RT PCR). Interleukin-10 (IL-10) was measured in the serum by enzyme-linked immunosorbent assay (ELISA). In every group, eight BN rats were retained for observing survival time. RESULTS: The survival times of recipients in the experimental group were prolonged compared with those in the control group. The rejective response occurred later and was milder in the experimental group. percentage of CD4, CD8, CD28 T-cells and Fkn mRNA expression were lower in the experimental group. While the serum IL-10 levels were higher in the experimental group than those in the control group. CONCLUSIONS: Acute rejective response after OLT was attenuated in the rats with Em infection, and the recipients' survival time was prolonged. Em may play a role in this process by elevating IL 10 secretion, decreasing the effector T cells, inhibiting the expression of Fkn, which lead to reduce the inflammatory cells infiltration into the liver. PMID- 22040487 TI - A molecular survey on cystic echinococcosis in Sinnar area, Blue Nile state (Sudan). AB - BACKGROUND: Cystic echinococcosis (CE) is a zoonosis caused by the cestodes of the Echinococcus species. Its life cycle involves dogs and other canids as definitive hosts for the intestinal tapeworm, as well as domestic and wild ungulates as intermediate hosts for the tissue-invading metacestode (larval) stage. The disease has a special impact on disadvantaged pastoralist communities and is listed now among the three top priority neglected tropical disease (NTD). Therefore, CE is a neglected disease even in high endemicity regions. This study aimed at investigation of the prevalence of CE in different animals slaughtered for food consumption in Sinnar area, Blue Nile states in Sudan. METHODS: A survey of CE in livestock was conducted from April 2009 to March 2011 in Sinnar area, Blue Nile state in Sudan. Location, parasitological status and fertility conditions were determined. In addition, 120 hydatid cysts (30 from camels, 62 from cattle and 28 from sheep) were examined by polymerase chain reaction (PCR) and mitochondrial gene sequencing for the genetic allocation of Echinococcus strains or species RESULTS: The prevalence of CE was 29.7% (30/101) in camels, 2.7% (62/2310) in cattle and 0.6% (26/4378) in sheep. It was shown that infection rates increased with age in camels, cattle and sheep. In camels, 67% (20/30) of the infected animals were aged between 2 - 5 years whereas 58% (36/62) of the infected cattle were > 5 years. In sheep, the prevalence rate was distributed equally between animals ranging 2 - 5 years and > 5 years. Even though multiple cysts were found in some animals, the average number of cysts per animal was close to 1 in all examined species. Lungs were found to be the predilection sites for the parasite in both camels and cattle, while most of the cysts found in sheep were located in the liver. About 63.4% of cysts encountered in camels were considered as large (5 - 7 cm), whereas those in cattle and sheep were medium (2 4 cm) and small (< 2 cm) respectively. The highest fertility rate was found in camel cysts with 85.4% (35/41) followed by cattle (50.0%, 32/64) and sheep (39.0%, 11/28). All examined cysts belonged to Echinococcus canadensis G6, which was confirmed to be the overwhelmingly predominant species in that area. CONCLUSION: The epidemiological situation in Sinnar area, Blue Nile state is characterized by intense transmission of Echinococcus canadensis G6, thereby closely resembling the situation in most other regions of Sudan. PMID- 22040488 TI - Distribution of the intermediate hosts of Echinococcus multilocularis in Shiqu County, Sichuan, China. AB - BACKGROUND: The rodentia and lagomorpha animals are the intermediate hosts of Echinococcus multilocularis, their distribution and infection of this parasite may facilitate the infection of definitive hosts such as dogs. The aim of this study was to determine the distribution of the intermediate hosts of Echinococcus multilocularis in Shiqu County, Sichuan, China. METHODS: A systematic sampling method was used to investigate the density of burrows of rodents and lagomorphs at 97 pasture sites in winter and summer pastureland and remote sensing (RS) technology was used to correlate their densities to the distribution of these animals in different landscape types. RESULTS: Based on the densities of Ochotona curzoniae, Microtus fuscus (dependent variable) and their burrow densities (independent variable) in survey points, regression equations were fitted respectively (Ochotona curzoniae, P < 0.0001, R(2) = 0.8705; Microtus fuscus, P < 0.0001, R(2) = 0.9736). Their burrow density in summer pastureland was higher than in winter pastureland (F = 36.65, P < 0.0001). The burrow densities of Ochotona curzoniae and Microtus fuscus in bareland and half-bareland are higher than in grassland (F = 7.73, P < 0.001). CONCLUSIONS: The regression relationship between the densities of Ochotona curzoniae and Microtus fuscus and their burrow densities indicate that the burrow densities could reflect the animal densities and that the burrow density was greater in summer pastureland than in winter pastureland. The main distribution areas of the intermediate hosts were in bareland and half-bareland. PMID- 22040489 TI - Molecular characterization of a signal-regulated kinase homolog from Echinococcus granulosus. AB - BACKGROUND: Cystic echinococcosis due to Echinococcus granulosus (E. granulosus) is one of the most important chronic helminthic diseases, especially in sheep/cattle-raising regions. The larval stage of the parasite forms a cyst that grows in the liver, lung, or other organs of the host. To ensure a long life in the host tissues, the parasite establishes complex inter-cellular communication systems between its host to allow its differentiation toward each larval stage. Recent studies have reported that this communication is associated with the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade in helminth parasites, and in particular that these protein kinases might serve as effective targets for a novel chemotherapy for cystic echinococcosis. The aim of the present study investigated the biological function of a novel ERK ortholog from E. granulosus, EgERK. METHODS: DNA encoding EgERK was isolated from protoscolices of E. granulosus and analyzed using the LA Taq polymerase chain reaction (PCR) approach and bioinformatics. Reverse transcription PCR (RT-PCR) was used to determine the transcription level of the gene at two different larval tissues. Western blotting was used to detect levels of EgERK protein. The expression profile of EgERK in protoscolices was examined by immunofluorescence. RESULTS: We cloned the entire Egerk genomic locus from E. granulosus. In addition, two alternatively spliced transcripts of Egerk, Egerk-A, and Egerk-B were identified. Egerk-A was found to constitutively expressed at the transcriptional and protein levels in two different larval tissues (cyst membranes and protoscolices). Egerk-A was expressed in the tegumental structures, hooklets, and suckers and in the tissue surrounding the rostellum of E. granulosus protoscolices. CONCLUSIONS: We have cloned the genomic DNA of a novel ERK ortholog from E. granulosus, EgERK (GenBank ID HQ585923), and found that it is constitutively expressed in cyst membrane and protoscolex. These findings will be useful in further study of the biological functions of the gene in the growth and development of Echinococcus and will contribute to research on novel anti echinococcosis drug targets. PMID- 22040490 TI - Curative effect of radiotherapy at various doses on subcutaneous alveolar echinococcosis in rats. AB - BACKGROUND: Alveolar echinococcosis (AE) is a disease in human and animals, and the cure rate is unsatisfactory. This study aimed to investigate the curative efficacy of different doses of locally applied radiotherapy on alveolar echinococcosis in rats. METHODS: Rats infected with Echinococcus multilocularis were randomly divided into 4 groups of 15 rats each: low-, middle-, and high irradiation groups and a control group. Rats in the control group underwent no treatment, while rats in the irradiation groups received 6-MeV radiotherapy at 20 Gy/8 f, 40 Gy/8 f, and 60 Gy/8 f respectively, once every 3 days for a total of 8 times. One month after radiotherapy, wet weight and AE vesicle inhibitory rate were detected in rats of each group. Histopathologic and ultrastructural observations of tissues with AE lesions were performed. RESULTS: In the treatment groups, an obvious inhibitory effect was found in AE rats; the inhibitory rates were 50%, 72%, and 82%, respectively. There were also statistical differences in pathological changes and average wet weight of the lesions compared with the control group (P < 0.05). In the treatment groups, injuries of various degrees were found in the ultrastructure of the laminated and germinal layers in the capsular wall of AE, and injury was most severe in the high-dose group. CONCLUSION: Radiotherapy has a dose-dependent inhibitory effect on the growth of AE. PMID- 22040491 TI - Genetic variation of the 8-kDa glycoprotein family from Echinococcus granulosus, Taenia multiceps and Taenia hydatigena. AB - BACKGROUND: Echinococcosis, coenurosis and cysticercosis are debilitating diseases which prevail in China. Immunological diagnosis of metacestodosis is important in disease control. The 8-kDa glycoproteins from taeniid cestodes have successfully been used for diagnosis of human cysticercosis in immunological assays. The aim of the present study was to investigate genetic variations and phylogenetic relationships of the 8-kDa proteins for evaluating the possibility of utilizing these proteins as diagnostic antigens for other metacestode infections. METHODS: The genes and complementary DNAs (cDNAs) encoding the 8-kDa proteins from Echinococcus (E.) granulosus, Taenia (T.) multiceps and T. hydatigena were amplified using PCR method. Their amplicons were cloned into the vector pMD18 and the positive clones were sequenced. Sequence data were analyzed with the SeqMan program, and sequence homology searches were performed using the BLAST program. Alignments were conducted using the ClustalX program, and the phylogenetic analyses were performed with the Protein Sequences Program and the Puzzle Program using the Neighbor-joining method. RESULTS: Fifteen, 18 and 22 different genomic DNA sequences were identified as members of the 8-kDa protein gene family from E. granulosus, T. multiceps and T. hydatigena, respectively. Eight, four and six different cDNA clones respectively from E. granulosus, T. multiceps and T. hydatigena were characterized. Analysis of these sequences revealed 54 unique 8-kDa protein sequences. Phylogenetic trees demonstrated that the taeniid 8-kDa proteins are clustered into eight clades at least: Ts18, Ts14, TsRS1, TsRS2, T8kDa-1, T8kDa-2, T8kDa-3 and T8kDa-4. CONCLUSION: We found that the gene family encoding for the taeniid 8-kDa antigens is comprised of many members with high diversity, which will provide molecular evidence for cross reaction or specific reaction among metacestode infections and may contribute to the development of promising immunological methods for diagnosis of metacestodosis. PMID- 22040492 TI - Pericyst may be a new pharmacological and therapeutic target for hydatid disease. AB - BACKGROUND: Most hydatid cysts with calcified walls are biologically and clinically silent and inactive. Transforming growth factor-beta 1 (TGF-beta1) plays a critical role in the calcification process of cells. The aim of this study was to assess the effect of modulating TGF-beta1 signaling on the calcification of hydatid cysts. METHODS: Pericyst cells isolated from hepatic hydatid cysts were cultured with osteogenic media. These cells were assessed for alkaline phosphatase activity and mineralization capacity using Alizarin Red staining. Cells were also treated with recombinant human TGF-beta1 and TGF-beta inhibitor, and the expression profiles of osteoblast markers (RUNX2, osterix, and osteocalcin) were analyzed using Western blotting. The effects of inhibiting TGF beta1 signaling on calcification of pericyst walls were assessed using different doses of TGF-beta inhibitor for 7 weeks in a preclinical disease model of liver cystic echinococcosis. RESULTS: Cells within the pericyst displayed high levels of alkaline phosphatase activity and mineralized nodule formation, as induced by osteogenic media. These activities, as well as expression profiles of osteoblast markers (RUNX2, osterix, and osteocalcin) could be inhibited by addition of recombinant human TGF-beta1 (rhTGF-beta1) and enhanced by TGF-beta inhibitor. In the animal model of cystic echinococcosis, inhibition of TGF-beta1 signaling increased calcification of the pericyst wall, which was associated with decreased cyst load index and lower viability of protoscoleces. CONCLUSIONS: Cells within the pericysts adopt an osteoblast-like phenotype and have osteogenic potential. Inhibition of TGF-beta1 signaling increases hydatid cyst calcification. Pharmacological modulation of calcification in pericysts may be a new therapeutic target in the treatment of hydatid disease. PMID- 22040493 TI - Rs548234 polymorphism at PRDM1-ATG5 region susceptible to rheumatoid arthritis in Caucasians is not associated with rheumatoid arthritis in Chinese Han population. AB - BACKGROUND: A previous study has shown that rs548234 polymorphism at PRDM1-ATG5 region is associated with rheumatoid arthritis (RA) in Caucasian populations. The aim of this study was to investigate the effect of rs548234 polymorphism at PRDM1 ATG5 region on susceptibility to RA in Chinese Han population. METHODS: We genotyped 848 RA patients and 1431 matched healthy controls for rs548234 single nucleotide polymorphism (SNP) with a predesigned TaqMan SNP genotyping assay. Association analyses were performed on the whole data set and on rheumatoid factors (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibody. Finally, we carried out combined analysis of rs548234 association with RA based on the published data. RESULTS: No significant difference in the genotype distribution between RA patients and healthy controls for rs548234 (C/T) polymorphism was found in Chinese Han population, neither in whole data set nor in stratified subsets, e.g. RF and anti-CCP status. Association analysis in different ethnic groups showed that rs548234 at PRDM1-ATG5 region was associated with RA in Caucasian ancestry but not in East Asian population. CONCLUSIONS: Our results showed no involvement of rs548234 at PRDM1-ATG5 region in the susceptibility or clinical relevance of RA in Chinese Han population. PMID- 22040494 TI - Factors influencing recovery of left ventricular structure in patients with chronic heart failure. AB - BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and beta-blockers (betaB) have beneficial effects on left ventricular (LV) remodeling, alleviate symptoms and reduce morbidity and mortality in patients with chronic heart failure (CHF). However the correlation between the d osages of ACE inhibitors, betaB, and recovery of LV structure remains controversial. Clinical factors associated with recovery of normal ventricular structure in CHF patients receiving medical therapy are poorly defined. Here we aimed to identify variables associated with recovery of normal or near-normal structure in patients with CHF. METHODS: We recruited 231 consecutive CHF outpatients, left ventricular ejection fraction (LVEF) <= 40% and left ventricular end diastolic diameter (LVEDD) > 55/50 mm (male/female), who were receiving optimal pharmacotherapy between January 2001 and June 2009, and followed them until December 31, 2009. They were divided into three groups according to LVEDD and whether they were still alive at final follow-up: group A, LVEDD <= 60/55 mm (male/female); group B, LVEDD > 60/55 mm (male/female); and group C, those who died before final follow-up. Apart from group C, univariate analysis was performed followed by Logistic multivariate analysis to determine the predictors of recovery of LV structure. RESULTS: A total of 217 patients completed follow-up, and median follow-up time was 35 months (range 6 - 108). Twenty-five patients died during that period; the all cause mortality rate was 11.5%. Group A showed clinical characteristics as follows: the shortest duration of disease and shortest QRS width, the lowest N terminal brain natriuretic peptide (NT-proBNP) at baseline, the highest dose of betaB usage, the highest systolic blood pressure (SBP), diastolic blood pressure (DBP) and the lowest New York Heart Association (NYHA) classification, serum creatinine, uric acid, total bilirubin and NT-proBNP after treatment. Logistic multivariate analysis was performed according to recovery or no recovery of LV structure. Data showed that LVEF at follow-up (P = 0.013), mitral regurgitation at baseline (P = 0.020), LVEDD at baseline (P = 0.031), and betaB dosage (P = 0.041) were independently associated with recovery of LV diameter. CONCLUSION: Our study suggests that four clinical variables may predict recovery of LV structure to normal or near-normal values with optimal drug therapy alone, and may be used to discriminate between patients who should receive optimal pharmacotherapy and those who require more aggressive therapeutic interventions. PMID- 22040495 TI - Combination of donor splenocyte transfusion with blockade of gammac signal synergizes to inhibit alloreactive T-cell proliferation and induces apoptosis. AB - BACKGROUND: The common gamma chain (gammac) plays a critical role in regulating proliferation, differentiation, and apoptosis of peripheral T-cells. It was previously confirmed that blocking the gammac signal can successfully induce transplant tolerance in a murine model. Here we investigated the potential mechanism. METHODS: Splenocytes from C57BL/6 mice were transfused into T-cell deficient Balb/c nude mice that were reconstituted with syngeneic wild-type T cells labeled with 5-carboxyfluorescein diacetate succinimidyl ester (CFSE). After 24 hours, recipients received i.p. injection of mixture of anti-gammac mAbs, or with isotype control IgG2a. The labeled T-cells were harvested from recipient spleens after 12 and 48 hours. T-cell proliferation and apoptosis were detected by flow cytometry. RESULTS: T-cell proliferation was markedly inhibited and apoptotic T cells could be detected at 12 hours after the mAbs injection. Proliferation was inhibited at 48 hours, but the proportion of apoptotic T-cells was not more than at 12 hours. In the control group, however, T-cells actively proliferated and no significant apoptosis was detected at either time point. CONCLUSIONS: The results suggested that blockade of gammac signals can synergize with donor splenocyte transfusion and lead to inhibition of antigen-specific T cell proliferation and induction of apoptotic T-cell death. This protocol may develop a novel approach to induce donor-specific tolerance. PMID- 22040496 TI - Current treatment status in patients with severe aortic valve stenosis and outcome of long term follow-up at advanced age: a Chinese single center study. AB - BACKGROUND: Surgical aortic valve replacement is the standard treatment for patients with severe aortic stenosis, but some registries have indicated that 30% to 60% of these patients are not treated surgically, usually due to advanced age and/or comorbidities. This single center study in China investigated the current treatment status in the patients with severe aortic stenosis and evaluated the long term clinical outcome in advanced age patients whether or not undergoing aortic valve replacement. METHODS: Clinical data of 867 consecutive patients with severe aortic stenosis between January 2000 and December 2006 were retrospectively analyzed. The patients >= 65 years old were followed up by telephone or information from medical records. The primary end-point was all cause mortality. RESULTS: The patients' average age was (52 +/- 19) years (range, 1 - 91 years), and 34% were women. The percentages of the patients aged < 15 years, between 15 and 34 years, between 35 and 54 years, between 55 and 64 years, between 65 and 74 years, and >= 75 years who underwent surgical aortic valve replacement were 82.3%, 87.2%, 88.8%, 78.2%, 65.3% and 22.2% respectively. In the patients (n = 256) >= 65 years old, 43.4% had New York Heart Association class III and IV symptoms, 39.1% had hypertension, 33.2% had coronary heart disease, and 3.1% had stroke. In the patients not undergoing aortic valve replacement, 1.6% had renal insufficiency, 4.7% had chronic obstructive pulmonary disease, 2.0% had critical hematopathy, and 0.4% had mammary cancer. A total of 186 (72.7%) patients finished the follow-up, and the average duration of the follow up was (60 +/- 26) months. In the patients between 65 and 74 years old, the total deaths and cardiac deaths in the patients undergoing aortic valve replacement decreased significantly compared with those with conservative treatment (10.3% vs. 53.7%, P < 0.001 and 6.3% vs. 50.7%, P < 0.001). Similarly, in the patients >= 75 years old, there was a significant difference between patients who had surgery and those who had conservative treatment in the total deaths and cardiac deaths (21.4% vs. 63.3%, P = 0.007 and 14.3% vs. 46.9%, P = 0.033). The total deaths in the patients aged between 65 and 74 years were significantly fewer compared with = 75 years old patients (25.4% vs. 54.0%, P < 0.001). Cox regression revealed that aortic valve replacement was the only independent predictor of mortality (HR 0.183; 95% CI, 0.101 - 0.332, P < 0.001). CONCLUSIONS: This single centre study showed that surgical aortic valve replacement was still the standard treatment for the patients with severe aortic stenosis and had a satisfying prognosis. However, the high risk patients with advanced age and comorbidities usually selected conservative treatment and had an unfavorable prognosis. PMID- 22040497 TI - Comparison of the effects of recombinant human endostatin and docetaxel on human umbilical vein endothelial cells in different growth states. AB - BACKGROUND: Recombinant human endostatin (rh-endostatin, Endostar) has been proved to be an inhibitor of angiogenesis. Docetaxel has been also considered as a common chemotherapeutic agent with inhibition of angiogenesis of malignancies. However, their function has been seldom compared and a best synergism protocol is not determined. This study aimed to compare the effects of two drugs, investigate their combined impact on human umbilical vein endothelial cells (HUVECs), a molecular basis and find ideal protocols to inhibit endothelial cell proliferation. METHODS: HUVECs on confluent growth or activated by vascular endothelial growth factor (VEGF) were treated by rh-endostatin or/and docetaxel at respective gradient concentration in following operations as cell proliferation determined by MTT assay, cell cycle distribution, apoptosis and markers of CD146, CD62E and CD105 detected by flow cytometery, the structure of the channel formed by HUVECs measured by tube formation count. RESULTS: Rh endostatin exhibited time dependent inhibition of proliferation while docetaxel showed both time and dose dependent inhibition. HUVECs accumulated in G(0)-G(1) with decreased numbers of cells in G(2) after a single treatment of rh-endostatin or that followed by docetaxel treatment. Cells accumulated in G(2) after both a single docetaxel and simultaneous administration. Both the number of cells in G(0)-G(1) and apoptotic cells were increased by docetaxel followed by rh endostatin treatment. The number of non-apoptotic cells at G(0)-G(1) was increased by first administering rh-endostatin then docetaxel. Sequential treatment of docetaxel followed by rh-endostatin resulted in the greatest increase in apoptosis (34.7%) and the second highest apoptosis was seen with simultaneous administration (18.2%). Expression of CD146 and CD105 on confluent HUVECs was reduced at certain doses of rh-endostatin and/or docetaxel. However, rh-endostatin reduced CD105 without any apparent impact on either CD146 or CD62E expression, whereas these markers were down-regulated by docetaxel after pre activation by VEGF. Rh-endostatin treatment maintained tube-like structures for a limited time. In contrast, docetaxel swiftly reduced tube formation. Simultaneous treatment, or docetaxel followed by rh-endostatin, exhibited a stronger inhibition on tube formation than either agent alone. CONCLUSIONS: Both rh endostatin and docetaxel can inhibit HUVEC proliferation while the high apoptotic rate after combined administration was probably owing to different sequent administration by docetaxel followed by rh-endostatin or simultaneous treatment. Both proliferation and adhesion molecules on HUVECs of confluent growth are down regulated by the two drugs. The rh-endostatin decreased proliferation markers, but only slightly modified adhesion molecules, while both markers were down regulated by docetaxel on HUVECs activated by VEGF. Rh-endostatin could maintain adhesion of HUVECs at first then induce cells apoptosis to damage tube formation. We hypothesize that it could lead to vascular normalization in short time. In contrast, docetaxel can suppress HUVEC proliferation, adhesion, and reduced tube formation swiftly due to its cytotoxicity. Combined treatments can induce a synergistic inhibition of tube formation. PMID- 22040498 TI - Visualization of Medpor implants using surface rendering. AB - BACKGROUND: The Medpor surgical implant is one of the easiest implants in clinical practice, especially in craniomaxillofacial surgery. It is often used as a bone substitute material for the repair of skull defects and facial deformities. The Medpor implant has several advantages but its use is limited because it is radiolucent in both direct radiography and conventional computed tomography, causing serious problems with visualization. METHODS: In this study, a new technique for visualizing Medpor implants was evaluated in 10 patients who had undergone facial reconstruction using the material. Continuous volume scans were made using a 16-channel tomographic scanner and 3D reconstruction software was used to create surface renderings. The threshold values for surface renderings of the implant ranged from -70 HU to -20 HU, with bone as the default. RESULTS: The shape of the implants and the spatial relationship between bone and implant could both be displayed. CONCLUSION: Surface rendering can allow successful visualization of Medpor implants in the body. PMID- 22040499 TI - Expression level of novel tumor suppressor gene FATS is associated with the outcome of node positive breast cancer. AB - BACKGROUND: Recently, we reported the identification of a previously uncharacterized and evolutionarily conserved gene, fragile-site associated tumor suppressor (FATS), at a frequently deleted region in irradiation (IR)-induced tumors. However, the role of FATS in breast cancer development and its clinical significance has not been defined. The aim of this study was to determine the role of FATS in breast cancer development and to evaluate its clinical significance in breast cancer. METHODS: The expression level of FATS mRNA was determined in 106 breast carcinomas and 23 paired normal breast tissues using quantitative real time reverse transcription-polymerase chain reaction (RT-PCR). The relationship between FATS expression and clinicopathological parameters were also analyzed. RESULTS: The mRNA level of FATS was down-regulated in breast cancer compared with paired normal tissues. Low expression of FATS was correlated with high nuclear grade. There was a tendency to a favorable outcome for patients with high expression of FATS (P = 0.346). However, low expression of FATS was associated with poor outcome of breast cancer patients with node positive (P = 0.011). Furthermore, the mRNA level of FATS showed an independent value in predicting the outcome of breast cancer patients with positive lymph nodes. CONCLUSION: FATS is involved in the carcinogenesis and development of breast cancer and could be a potential biomarker and prognostic factor for breast cancer therapy. PMID- 22040500 TI - Molecular mechanism of icariin on rat asthmatic model. AB - BACKGROUND: Effects of icariin on airway inflammation in asthmatic rats and the intervention of LPS induced inflammation are interfered with the machanism of icariin. Our study aimed to observe the effect of icariin on ovalbumin-induced imbalance of Th1/Th2 cytokine expression and its mechanism. METHODS: Sixty male SD rats were randomly divided into control group (PBS), asthma group (ovalbumin (OVA)-induced), dexamethasone group, and OVA+icariin low, medium and high dose groups (5, 10, 20 mg/kg, respectively). Each group had ten rats. The model of OVA sensitization was a rat asthma model. Enzyme-linked immunosorbent assay (ELISA) method was used to observe the effects of icariin on interleukin-4 (IL-4) and inerferon gamma (IFN-gamma) in rats' lung tissue. Immunohistochemical staining was applied to detect the intervention effects of icariin on T cells (T-bet) and gatabinding protein 3 (GATA-3) in rat pulmonary tissue. Realtime RT-PCR was used to observe the intervention effects of icariin on T-bet and GATA-3 mRNA expression in rat pulmonary tissue and spleen lymphocytes. Western blotting was used to observe the icariin intervention effects on T-bet, GATA-3 and nuclear factor-Kappa B (NF-kappaB) p65 protein expressions in rat pulmonary tissue. RESULTS: The ELISA results from pulmonary tissue showed that IL-4 expression was significantly reduced (P < 0.05), while the IFN-gamma expression increased but not significantly when we compared OVA+icariin medium and high dose groups with the asthma group. Immunohistochemical staining of pulmonary tissue showed that the GATA-3 decreased significantly while the T-bet staining did not change in the OVA+icariin high dose group. In pulmonary tissue and spleen lymphocytes T-bet and GATA-3 mRNA expressions were significantly reduced (P < 0.05) in icariin treatment groups compared with the asthma model group. GATA-3 and T-bet mRNA in rat spleen lymphocytes in the asthma group were higher than in the control group. GATA-3 mRNA expression in pulmonary tissue significantly decreased (P < 0.05) while T-bet mRNA expression decreased but not significantly in the icariin treatment group compared with the asthma group. T-bet and GATA-3 protein expressions in pulmonary tissue increased significantly compared with the asthma group, which meant that icariin could inhibit the increase of GATA-3 protein, but not of T-bet. The bronchus, blood vessels and periphery pulmonary tissue had infiltration of inflammatory cells in the OVA+icariin high dose group while NF kappaB p65 cells were reduced, and expression of NF-kappaB p65 in this group was less than in the asthma group. The expression of total p65 protein decreased with icariin treatment while the expression of cytoplasmic p65 protein increased. CONCLUSIONS: Icariin could regulate the imbalance of Th1/Th2 cytokines in asthmatic rat pulmonary tissue. Icariin could regulate the imbalance of Th1/Th2 associated transcription factors T-bet and GATA-3 in asthmatic rat pulmonary tissue and spleen lymphocytes. Icariin could inhibit the activation of NF-kappaB p65 protein in asthmatic rat pulmonary tissue. PMID- 22040501 TI - Relative apparent diffusion coefficient: a promising tool to differentiate metastatic from benign lymph nodes in animal models. AB - BACKGROUND: Diffusion-weighted imaging has been widely used to differentiate the character of lymphadenopathy. But there are significant differences between prior studies. The aim of the study was to compare the benefit of apparent diffusion coefficient (ADC) and rADC in the differentiation of metastatic and benign lymph nodes in a rabbit model. METHODS: Two observers independently measured ADCs in quadriceps of every rabbit on diffusion-weighted images with different sizes of regions of interest (ROI). The appropriate ROI for rADC was determined using the interobserver coefficient. rADC was calculated by ADC(lesion)/ADC(reference site). Receiver operating characteristics (ROC) analysis was performed to compare the diagnostic value of the ADC values and rADC values in differentiating metastatic from benign lymph nodes. RESULTS: When the ROIs included five pixels, the ICC was 0.816, indicating a good interobserver agreement. The differences of ADC and rADC values between metastatic and benign lymph nodes were both statistically significant. The area under the ROC curve was greater for the rADC than for the ADC. With the rADC criteria of 0.640, the sensitivity and specificity for differentiating metastatic from benign lymph nodes were 93% and 90%, respectively. CONCLUSION: As a reference site, muscles reveal a good repeatability using a small ROI and the rADC may improve diagnostic accuracy for detecting metastatic nodes in animal models. PMID- 22040502 TI - Reassessment of the predictive role of perivesical fat invasion in invasive bladder cancer prognosis in 151 Chinese patients. AB - BACKGROUND: Perivesical fat invasion is considered as an important prognostic factor for bladder cancer. However, the predictive role of perivesical fat invasion in invasive bladder cancer prognosis has never been reported in Chinese patients. The aim of the study was to assess the predictive value of perivesical fat invasion for prognoses of T2 and T3 bladder cancer in Chinese patients. METHODS: One hundred and fifty-one patients who underwent radical cystectomy for pT2-3N0M0 invasive bladder cancer from 2001 to 2007 were studied. Cancer-specific survival rate (CSS) and recurrence-free survival rate (RFS) were compared between the pT2 and pT3 patient groups. Other clinicopathological parameters were also retrospectively analyzed by univariate and multivariate analyses to identify the independent predictor for the prognoses of this cohort. RESULTS: Average patient age at surgery was 58 years. Ninety (60.3%) patients had grade I and II disease. During follow-up (median 66 months), 27 patients (17.9%) had tumor recurrence and 18 (11.9%) died of bladder cancer. In the univariate analysis, the CSS and RFS curves between T2 and T3 patients showed no significant difference (P = 0.756 and 0.354, respectively). Multivariate Cox regression showed that histological classification and grade were independent predictors for CSS, while grade was the sole independent predictor for RFS. CONCLUSIONS: For this group of Chinese patients, perivesical fat invasion did not demonstrate a statistically significant difference in prognosis between T2 and T3 patients. Nontransitional cell carcinoma (non-TCC) and high-grade patients had short CSS, and patients with high-grade tumor had higher recurrent risk. PMID- 22040503 TI - Efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma. AB - BACKGROUND: The tyrosine kinase inhibitors (TKIs) sunitinib, the first targeted agent for the first line treatment of metastatic renal cell carcinoma (RCC), targets the vascular endothelial growth factor (VEGF) pathway. The objective of this study was to investigate the efficacy and safety of sunitinib in treating metastatic clear-cell RCC and to confirm if hypertension is an effective predictive factor. METHODS: A total of 36 patients with metastatic RCC were enrolled between June 2008 and December 2010. Among them 29 cases were first line therapy and 7 cases were in progression on first-line cytokine or sorafinib therapy. The pathology of all patients was confirmed predominant in clear cell type. Sunitinib mono-therapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients; and 3 patients were administered with 37.5 mg/d continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. We divided patients into Group A and Group B according to the blood pressure level. RESULTS: The median follow-up was 15 months (10 cycles, range 1.5 - 30.0 months (1 - 20 cycles)). Ten patients (29.4%) achieved partial responses (PR); 23 patients (67.6%) demonstrated stable disease (SD) lasting >= 2 cycles. Seventeen patients (50%) developed progressive disease (PD) during follow-up. The median progression-free survival (PFS) was 15 months (range 3.0 - 28.5) months. A total of 9 patients died; the overall survival has not been reached; the median survival time of the deceased patients was 13 months (range 7 - 24) months. The most common adverse events were hand-foot syndrome (77.8%), thrombocytopenia (75.0%), hypertension (61.1%) and diarrhea (46.0%). Most adverse events were reversible by treatment interruption. Twenty-two patients (61.1%) developed hypertension; and hypertension was associated with a long time to disease progression and long overall survival (P = 0.004, 0.000, respectively). CONCLUSIONS: The results of this study demonstrate the efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic clear cell RCC. Further, sunitinib associated hypertension may be a strong predictive marker for treatment efficacy in metastatic RCC. PMID- 22040504 TI - Natural herbal medicine Lianhuaqingwen capsule anti-influenza A (H1N1) trial: a randomized, double blind, positive controlled clinical trial. AB - BACKGROUND: The 2009 influenza A (H1N1) virus infection is associated with the high risk of severe complications and is spreading more rapidly throughout the world than other reported seasonal influenzas. This study aimed to evaluate the efficacy and safety of the nature herbal medicine Lianhuaqingwen capsule (LHC) in patients infected with influenza A (H1N1) virus. METHODS: A total of 244 patients aged 16 - 65 years confirmed with influenza A (H1N1) virus infection by the real time RT-PCR were randomized to one of two treatment groups of 122 patients each. Each group assigned to receive either LHC or Oseltamivir for five days and observation for seven days. The patients were enrolled within 36 hours of illness onset if they had an axillary temperature of >= 37.4 degrees C and with at least one of the following symptoms: nasal obstruction, runny nose, cough, sore throat, fatigue, headache, myalgia, chills and sweating. The primary end point was the duration of illness. RESULTS: Of 244 patients, 240 (98.36%) patients with a median age 21 years completed the study between October 24, 2009 and November 23, 2009. There were no significant overall differences between LHC treated and Oseltamivir treated patients in the median duration of illness (LHC 69 hours vs. Oseltamivir 85 hours P > 0.05) or the median duration of viral shedding (LHC 103 hours vs. Oseltamivir 96 hours, P > 0.05). However, it was worthwhile to note that LHC significantly reduced the severity of illness and the duration of symptoms including fever, cough, sore throat, and fatigue (P < 0.05). Both study medications were well tolerated. No drug related serious adverse events occurred during the study. CONCLUSIONS: Compared with Oseltamivir, LHC achieved a similar therapeutic effectiveness reduction of the duration of illness and duration of viral shedding. Therefore, LHC might be an alternative therapeutic measure for influenza A (H1N1) virus infections. PMID- 22040505 TI - Enrichment of breast cancer stem cells using a keratinocyte serum-free medium. AB - BACKGROUND: Keratinocyte serum-free medium (K-SFM) is a defined medium used to support the growth of primary keratinocytes and embryonic stem cell. The aim of this research was to optimize enrichment of breast cancer stem cells (CSCs) using K-SFM. METHODS: A K-SFM was used to enrich CSCs from two breast cancer cell lines and a primary culture of breast cancer. RPMI-1640 supplemented with 10% fetal calf serum (FCS) was used as a control. CSCs were identified with flow cytometry using CD44(+)/CD24(-) as molecular markers. The expression of a variety of CSC markers (Oct-4, ABCG2, Nanog, N-cadherin, and E-cadherin) was analyzed with real time PCR. RESULTS: Much higher percentage of CSCs was achieved with K-SFM: 17.3% for MCF-7 cells, 17.4% for SKBR-3, and 20.0% for primary breast cancer culture. Less than 1% CSC was achieved using RPMI-1640 supplemented with 10% FCS. In comparison to the CSCs obtained with RPMI-1640, CSCs in the K-SFM expressed higher levels of Oct-4, ABCG2, Nanog and N-cadherin, and lower level of E cadherin. CONCLUSION: K-SFM is an optimal culture medium to maintain and to enrich breast CSCs. PMID- 22040506 TI - Effects of different pacing algorithms on cumulative ventricular pacing proportion in patients with pacemakers. AB - BACKGROUND: It is well known that increased cumulative ventricular pacing proportion (CumVP%) is one of the most important causes for adverse cardiovascular events. Therefore, how to reduce CumVP% has been a treatment issue in recent years. This study aimed to investigate the effects of different pacing algorithms on CumVP% in patients with pacemakers. METHODS: Pacemakers with three pacing algorithms, i.e., conventional dual chamber rate adaptive pacing (DDDR), search atrioventricular conduction plus (SAV+) and managed ventricular pacing (MVP), were implanted in 42 patients including 41 with bradycardia arrhythmias and one with ventricular tachycardia. Pacemakers were programmed to work in conventional DDDR, SAV+ and MVP during the follow-up periods of the first, the second and the third month. In each pacing algorithm, the time percentages of four pacing and sense status including atrial sense-ventricular sense (AS-VS), atrial sense-ventricular pacing (AS-VP), atrial pacing-ventricular sense (AP-VS) and atrial pacing-ventricular pacing (AP-VP) were calculated. Cumulative ventricular pacing proportions were compared in the three pacing algorithms in the first, the second and the third month postoperatively. RESULTS: In the DDDR algorithm AS-VS, AS-VP, AP-VS and AP-VP were 2.4%, 52.3%, 2.5% and 42.8% respectively, while in SAV+ they were 19.3%, 34.9%, 33.9% and 12.0%, in MVP they were 38.9%, 13.2%, 41.6% and 6.4%. In the above the DDDR, SAV+ and MVP algorithms, cumulative ventricular pacing proportions were 95.1%, 46.9% and 19.6%, respectively (P < 0.05) and the percentages of CumVP% < 40% in patients were 0, 23.8% and 95.2.0% (P < 0.05). CONCLUSIONS: Compared with the conventional DDDR algorithm, both SAV+ and MVP significantly reduced the CumVP%, especially the MVP algorithm. Patients may benefit from MVP algorithm due to reduced CumVP%. PMID- 22040507 TI - A historical view of alveolar echinococcosis, 160 years after the discovery of the first case in humans: part 1. What have we learnt on the distribution of the disease and on its parasitic agent? AB - Since the first 2 cases observed in southern Germany and the correct identification of a parasite at the origin of the disease by the famous scientist Rudolf Virchow in 1855, the borders of the endemic area of alveolar echinococcosis (AE) have never stopped to expand. The parasite was successively recognized in Switzerland, then in Russia, Austria and France which were long considered as the only endemic areas for the disease. Cases were disclosed in Turkey in 1939; then much attention was paid to Alaska and to Hokkaido, in Japan. The situation totally changed in 1991 after the recognition of the Chinese endemic areas by the international community of scientists. The world map was completed in the beginning of the 21st century by the identification of AE in most of the countries of central/eastern Europe and Baltic States, and by the recognition of cases in central Asia. Up to now, the disease has however never been reported in the South hemisphere and in the United Kingdom. In the mid 1950s, demonstration by Rausch and Schiller in Alaska, and by Vogel in Germany, of the distinction between 2 parasite species responsible respectively for cystic echinococcosis ("hydatid disease") and AE put an end to the long-lasting debate between the "dualists", who believed in that theory which eventually proved to be true, and the "unicists", who believed in a single species responsible for both diseases. At the end of the 20th century, molecular biology fully confirmed the "dualist" theory while adding several new species to the initially described E. granulosus; within the past decade, it also confirmed that little variation existed within Echinococcus (E.) multilocularis species, and that AE-looking infection in some intermediate animal hosts on the Tibetan plateau was indeed due to a new species, distinct from E. multilocularis, named E. shiquicus. Since the 1970s, the unique ecological interactions between the landscape, the hosts, and E. multilocularis have progressively been delineated. The important role of the rodent/lagomorph reservoir size for the maintenance of the parasite cycle has been recognized within the last 2 decades of the 20th century. And the discovery of a close relationship between high densities of small mammals and particularities in land use by agriculture/forestry has stressed the responsibility of political/economic decisions on the contamination pressure. Urbanization of foxes in Europe and Japan and the major role of dogs in China represent the new deals at the beginning of the 21st century regarding definitive hosts and prevention measures. PMID- 22040508 TI - Treatment of intracranial hydatid cysts. AB - BACKGROUND: Echinococcosis is still endemic in many countries, including China, where it is especially prevalent in the northwest. The aim of this study was to enrich the international literature about the treatment of intracranial hydatid cysts. METHODS: We retrospectively reviewed the clinical features, radiological manifestations, and surgical outcome of 97 patients with intracranial hydatid cysts, who received surgical treatment at the Neurosurgical Department of First Affiliated Hospital of Xinjiang Medical University from 1985 to 2010 and followed up the patient via sending a questionnaire or telephone contact. Clinical outcome was evaluated using the Karnofsky Performance Scale Index. RESULTS: Headache and vomiting were the most common initial symptoms in our patients. Neurological deficits caused by the mass effect of the cysts were seen in 82 cases. On the X ray, significant bone erosion was seen in only two cases with epidural hydatid cysts. Round-shaped and thin-walled homogeneous low-density cystic lesions without surrounding edema and enhancement were the main findings on computerized tomography (CT) in 95 patients with intraparenchymal hydatid cysts, while two cases with epidural hydatid cysts presented as a heterodensity lesions. On magnetic resonance imaging (MRI), hydatid cyst presented as a round-shaped low signal lesion in T1-weighted images and high signal lesion in T2-weighted images, without enhancement after contrast media injection, while the two cases with epidural cysts presented as mixed signal masses. Surgical removal of cyst was performed in all cases. Total removal was achieved in 93 cases without rupturing the cyst wall. Only two cysts ruptured during the dissection, resulting in two surgery-related mortalities. There was no other additional neurological deficit caused directly by surgery. In 97.2% of the patients, the Karnofsky Performance Scale score was 80 to 90 at the last follow-up. CONCLUSIONS: Intracranial hydatid cyst is still a main cause of increased intracranial pressure among the patients in endemic areas for echinococcosis. CT and MRI are the best diagnostic methods and surgery is the treatment of choice for intracranial hydatid cysts. PMID- 22040510 TI - Nail digital dermoscopy (onychoscopy) in the diagnosis of onychomycosis. AB - BACKGROUND: Distal subungual onychomycosis and traumatic onycholysis are the most common causes of toenail abnormalities, and differential diagnosis is often impossible without mycology. OBJECTIVES: To identify and describe dermoscopic signs specific for distal subungual onychomycosis that could facilitate its diagnosis and differentiation from traumatic mycologically negative onycholysis and to determine the sensitivity and specificity of these dermoscopic features. METHODS: We performed a retrospective study at the Outpatient Consultation for Nail Diseases of the Department of Dermatology of the University of Bologna. Dermoscopic digital images of 57 consecutive patients who underwent global photography, videodermoscopy and mycological examination for onycholysis of a single toenail between 1 December, 2010 and 30 June, 2011, were evaluated and compared. Digital dermoscopic images of onycholysis of the great toenail were evaluated for the presence of peculiar dermoscopic features. The presumptive dermoscopic diagnosis was compared with results of mycology. RESULTS: Evaluation of videodermoscopic images allowed us to identify three recurring peculiar dermoscopic features, two of which were present only in distal subungual onychomycosis (jagged proximal edge with spikes of the onycholytic area and longitudinal striae) and one only in traumatic onycholysis (linear edge - without spikes - of the onycholytic area). CONCLUSIONS: We found distinctive dermoscopic signs that are exclusive to distal subungual onychomycosis and to traumatic onycholysis. Detection of these signs is simple and can, in selected cases, help to avoid mycology. PMID- 22040511 TI - Synthesis and properties of a star-shaped poly(epsilon-caprolactone)-ibuprofen conjugate. AB - A series of novel star-shaped poly(epsilon-caprolactone) (PCL) biodegradable polyesters were synthesized through ring-opening polymerization of epsilon caprolactone in the presence of a poly(amidoamine) (PAMAM) dendrimer initiator. The polymers (PAMAM/PCLs) were obtained with a high yield (92%) and a number average molecular weight of up to 14 000 g/mol. The nonlinear structure of PAMAM/PCLs was confirmed by nuclear magnetic resonance, gel-permeation chromatography, thermogravimetric analysis and differential scanning calorimetry. Thermal analysis indicated that the star-shaped PAMAM/PCLs had a melting point, degree of crystallinity, glass transition temperature and maximum decomposition temperature all lower than those of linear PCL. Ibuprofen (IBU), a popular non steroidal anti-inflammatory drug, was co-valently (ester) bonded to the PAMAM/PCL molecules using the DCC/DMAP coupling method (DCC, N,N'-dicyclohexylcarbodiimide; DMAP, 4-(dimethylamino)pyridine). A high drug content (33.1 mol%) in the conjugate was obtained. The in-vitro drug-release profiles of IBU from the PAMAM/PCL/IBU conjugate were examined and found adequate for drug-carrier applications of our star-shaped polymers. PMID- 22040512 TI - Quantifying experts' uncertainty about the future cost of exotic diseases. AB - Since the foot-and-mouth disease outbreak of 2001 in the United Kingdom, there has been debate about the sharing, between government and industry, both the costs of livestock disease outbreaks and responsibility for the decisions that give rise to them. As part of a consultation into the formation of a new body to manage livestock diseases, government veterinarians and economists produced estimates of the average annual costs for a number of exotic infectious diseases. In this article, we demonstrate how the government experts were helped to quantify their uncertainties about the cost estimates using formal expert elicitation techniques. This has enabled the decisionmakers to have a greater appreciation of government experts' uncertainty in this policy area. PMID- 22040513 TI - Photosynthetic pathway and ecological adaptation explain stomatal trait diversity amongst grasses. AB - * The evolution of C(4) photosynthesis in plants has allowed the maintenance of high CO(2) assimilation rates despite lower stomatal conductances. This underpins the greater water-use efficiency in C(4) species and their tendency to occupy drier, more seasonal environments than their C(3) relatives. * The basis of interspecific variation in maximum stomatal conductance to water (g(max) ), as defined by stomatal density and size, was investigated in a common-environment screening experiment. Stomatal traits were measured in 28 species from seven grass lineages, and comparative methods were used to test for predicted effects of C(3) and C(4) photosynthesis, annual precipitation and habitat wetness on g(max) . * Novel results were as follows: significant phylogenetic patterns exist in g(max) and its determinants, stomatal size and stomatal density; C(4) species consistently have lower g(max) than their C(3) relatives, associated with a shift towards smaller stomata at a given density. A direct relationship between g(max) and precipitation was not supported. However, we confirmed associations between C(4) photosynthesis and lower precipitation, and showed steeper stomatal size-density relationships and higher g(max) in wetter habitats. * The observed relationships between stomatal patterning, photosynthetic pathway and habitat provide a clear example of the interplay between anatomical traits, physiological innovation and ecological adaptation in plants. PMID- 22040514 TI - Item analysis and differential item functioning of a brief conduct problem screen. AB - Research has shown that boys display higher levels of childhood conduct problems than girls, and Black children display higher levels than White children, but few studies have tested for scalar equivalence of conduct problems across gender and race. The authors conducted a 2-parameter item response theory (IRT) model to examine item characteristics of the Authority Acceptance scale from the Teacher Observation of Classroom Adaptation-Revised (AA-TOCA-R; L. Larsson-Werthamer, S. G. Kellam, & L. Wheeler, 1991) in 8,820 kindergarten children and estimated the degree of differential item functioning (DIF) by gender and race/urban status. The mean level of latent conduct problems was best represented by behaviors such as being stubborn, breaking rules, and being disobedient, whereas breaking things and taking others' property best represented the construct at one standard deviation above the mean. DIF by gender was detected, such that at equivalent levels of latent conduct problems, males received more endorsements of overt behaviors from teachers, whereas females received more endorsements of nonphysical behaviors. Moreover, overt behaviors were better discriminators of latent conduct problems for males, and nonphysical behaviors were better discriminators of latent conduct problems for females. Differences across race/urban status were not found to be conceptually meaningful. The authors' analyses also suggest that the item scaling of the AA-TOCA-R may be best represented by 5e categories instead of 6. These findings provide support for the use of IRT modeling to examine item characteristics of conduct problem scales and DIF to test for scalar equivalence across diverse subpopulations. PMID- 22040515 TI - Construct validity and case validity in assessment. AB - Clinical assessment relies on both construct validity, which focuses on the accuracy of conclusions about a psychological phenomenon drawn from responses to a measure, and case validity, which focuses on the synthesis of the full range of psychological phenomena pertaining to the concern or question at hand. Whereas construct validity is grounded in understanding causal influences of a distinct phenomenon on responses to various measures and life contexts, case validity encompasses the joint influences of multiple phenomena on individuals' responses. Two sets of distinctions essential to understanding psychological phenomena, hence to understanding construct validity, are (a) implicit and explicit versions of personality constructs and (b) ability and personality as versions of constructs measured by performance tests presenting maximal and typical conditions, respectively. Since both implicit and explicit versions of constructs interface with maximal or typical performance conditions, case validity requires systematic inclusion of these distinctions in assessment protocols. PMID- 22040516 TI - Comparison of deck- and trial-based approaches to advantageous decision making on the Iowa Gambling Task. AB - We compared the original deck-based model of advantageous decision making assessed with the Iowa Gambling Task (IGT) with a trial-based approach across behavioral and physiological outcomes in 33 younger adults (15 men, 18 women; 22.2 +/- 3.7 years of age). One administration of the IGT with simultaneous measurement of skin conductance responses (SCRs) was performed and the two methods applied: (a) the original approach of subtracting disadvantageous picks of Decks A and B from advantageous picks of Decks C and D and (b) a trial-based approach focused on the financial outcome for each deck leading up to the trial in question. When directly compared, the deck-based approach resulted in a more advantageous behavioral profile than did the trial-based approach. Analysis of SCR data revealed no significant differences between methods for physiological measurements of SCR fluctuations or anticipatory responses to disadvantageous picks. Post hoc investigation of the trial-based method revealed Deck B contributed to both advantageous and disadvantageous decision making for the majority of participants. When divided by blocks of 20, the number of advantageous to disadvantageous choices reversed as the task progressed despite the total number of picks from Deck B remaining high. SCR fluctuations for Deck B, although not significantly different from the other decks, did show a sharp decline after the first block of 20 and remained below levels for Decks C and D toward the end of the task, suggesting that participants may have gained knowledge of the frequency of loss for this deck. PMID- 22040517 TI - Metabonomics-based omics study and atherosclerosis. AB - Atherosclerosis results from dyslipidemia and systemic inflammation, associated with the strong metabolism and interaction between diet and disease. Strategies based on the global profiling of metabolism would be important to define the mechanisms involved in pathological alterations. Metabonomics is the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification. Metabonomics has been used in combination with proteomics and transcriptomics as the part of a systems biology description to understand the genome interaction with the development of atherosclerosis. The present review describes the application of metabonomics to explore the potential role of metabolic disturbances and inflammation in the initiation and development of atherosclerosis. Metabonomics-based omics study offers a new potential for biomarker discovery by disentangling the impacts of diet, environment and lifestyle. PMID- 22040518 TI - Development and evaluation of a single-step multiplex PCR to differentiate the aquatic stages of morphologically similar Aedes (subgenus: Stegomyia) species. AB - OBJECTIVE: To develop a single-step multiplex PCR to differentiate the aquatic stages of Aedes aegypti, Aedes albopictus and Aedes vittatus collected from different breeding spots in arbovirus endemic/epidemic areas and to detect the most abundant species by the multiplex PCR. METHODS: Aquatic stages of different mosquito species were sampled by inspecting artificial and natural breeding sites in domestic and peridomestic areas. DNA was isolated from different stages of the three Aedes species. Using novel primers based on 18S rDNA sequence, a single step multiplex PCR was developed to clearly distinguish the three Aedes species. It was then evaluated in the aquatic stages of Aedes species collected from different areas. RESULTS: A total of 1150 aquatic stages were collected from 294 breeding spots, of which 156 contained Aedes species. Discarded tires were the major breeding spots of Aedes species. The aquatic stages were clustered into 230 pools; Ae. albopictus was detected in the largest number of pools, followed by Ae. aegypti and Ae. vittatus. CONCLUSIONS: The Multiplex PCR clearly differentiated the aquatic stages of the three Aedes species and detected that Ae. albopictus was most profuse in different breeding spots surveyed, hence indicating to be the main vector in this region. So control measures can be designed against Ae. albopictus at an early stage to prevent any arboviral outbreak. This method is a convenient tool for precise identification of Aedes vectors during entomological surveys in arbovirus endemic/epidemic areas where several species coexist. PMID- 22040519 TI - The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats. AB - BACKGROUND/OBJECTIVE: This study was designed to evaluate the potential chemopreventive activities of Ginkgo biloba extract (EGb) and Silybum marianum extract (silymarin) against hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) in rats. METHODS: Rats were divided into 6 groups. Group 1 served as normal control rats. Group 2 animals were intragastrically administrated NDEA at a dose of 10 mg/kg five times a week for 12 weeks to induce hepatocellular carcinoma (HCC). Groups 3 and 4 animals were pretreated with silymarin and EGb respectively. Groups 5 and 6 animals were posttreated with silymarin and EGb respectively. The investigated parameters in serum are alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and vascular endothelial growth factor (VEGF). The investigated parameters in liver tissue are malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and comet assay parameters. RESULTS: In NDEA group, MDA level was elevated with subsequent decrease in GSH level and SOD, GPx and GR activities. In addition, NDEA group revealed a significant increase in serum ALT, AST and GGT activities and VEGF level. Furthermore, NDEA administrated animals showed a marked increase in comet assay parameters. These biochemical alterations induced by NDEA were confirmed by the histopathological examination of rat livers intoxicated with NDEA that showed an obvious cellular damage and well differentiated HCC.In contrast, silymarin+NDEA treated groups (3&5) and EGb+NDEA treated groups (4&6) showed a significant decrease in MDA level and a significant increase in GSH content and SOD, GPx and GR activities compared to NDEA group. Silymarin and EGb also beneficially down-regulated the increase in serum ALT, AST, GGT activities and VEGF level induced by NDEA. In addition, silymarin and EGb significantly decreased comet assay parameters. Histopathological examination of rat livers treated with either silymarin or EGb exhibited an improvement in the liver architecture compared to NDEA group. CONCLUSIONS: The obtained findings suggested that silymarin and EGb may have beneficial chemopreventive roles against hepatocarcinogenesis through their antioxidant, antiangiogenic and antigenotoxic activities. PMID- 22040520 TI - The dipeptide Phe-Phe amide attenuates signs of hyperalgesia, allodynia and nociception in diabetic mice using a mechanism involving the sigma receptor system. AB - BACKGROUND: Previous studies have demonstrated that intrathecal administration of the substance P amino-terminal metabolite substance P1-7 (SP1-7) and its C terminal amidated congener induced antihyperalgesic effects in diabetic mice. In this study, we studied a small synthetic dipeptide related to SP1-7 and endomorphin-2, i.e. Phe-Phe amide, using the tail-flick test and von Frey filament test in diabetic and non-diabetic mice. RESULTS: Intrathecal treatment with the dipeptide increased the tail-flick latency in both diabetic and non diabetic mice. This effect of Phe-Phe amide was significantly greater in diabetic mice than non-diabetic mice. The Phe-Phe amide-induced antinociceptive effect in both diabetic and non-diabetic mice was reversed by the sigma1 receptor agonist (+)-pentazocine. Moreover, Phe-Phe amide attenuated mechanical allodynia in diabetic mice, which was reversible by (+)-pentazocine. The expression of spinal sigma1 receptor mRNA and protein did not differ between diabetic mice and non diabetic mice. On the other hand, the expression of phosphorylated extracellular signal-regulated protein kinase 1 (ERK1) and ERK2 proteins was enhanced in diabetic mice. (+)-Pentazocine caused phosphorylation of ERK1 and ERK2 proteins in non-diabetic mice, but not in diabetic mice. CONCLUSIONS: These results suggest that the spinal sigma1 receptor system might contribute to diabetic mechanical allodynia and thermal hyperalgesia, which could be potently attenuated by Phe-Phe amide. PMID- 22040521 TI - Effects of ketoconazole and valproic acid on the pharmacokinetics of the next generation NNRTI, lersivirine (UK-453,061), in healthy adult subjects. AB - AIMS: To investigate the effect of inhibitors of cytochrome P450 (CYP) 3A4 and glucuronidation (UGT2B7) on the pharmacokinetics of lersivirine (UK-453,061), a next generation non-nucleoside reverse transcriptase inhibitor with a unique resistance profile, and to investigate the safety and tolerability of co administration of lersivirine with these inhibitors. METHODS: Two open-label, randomized, placebo-controlled, crossover studies were conducted in healthy subjects. Study 1 investigated the effect of ketoconazole (400 mg once daily) on the pharmacokinetics of lersivirine (250 mg once daily). Subjects received ketoconazole 400 mg once daily or placebo on days 1-2 and received lersivirine 250 mg once daily and ketoconazole 400 mg once daily or placebo on days 3-9. Study 2 investigated the effect of valproic acid (VPA, sodium valproate, 1000 mg once daily) on the PK of lersivirine (500 mg once daily). On days 1-7, subjects received lersivirine 500 mg once daily plus either VPA 1000 mg or placebo. RESULTS: Compared with lersivirine alone, co-administration with ketoconazole increased the lersivirine mean area under the curve (AUC(0,24 h)) and maximum plasma concentration (C(max) ) by 82% (90% CI 74%, 91%) and 61% (90% CI 41%, 83%), respectively. VPA increased the mean lersivirine AUC(0,24 h) by 25% (90% CI 16%, 35%), with little effect on C(max) (2.5%, 90% CI -9%, 16%). There were no serious adverse events and no treatment-related discontinuations from either study. CONCLUSIONS: Inhibition of CYP3A4 and UGT2B7 by ketoconazole increased lersivirine exposure. Inhibition of UGT2B7-mediated glucuronidation by VPA had a modest effect on lersivirine exposure. Co-administration of lersivirine with either ketoconazole or VPA appeared to be well tolerated. PMID- 22040522 TI - Unilateral thalamic infarction presenting as vertical gaze palsy: a case report. AB - INTRODUCTION: Vertical gaze palsy is a recognized manifestation of midbrain lesions. It rarely is a consequence of unilateral thalamic infarction. CASE PRESENTATION: We report the case of a 48-year-old African-American woman who presented to our facility with vertical gaze palsy and evidence of left medial thalamic infarct on diffusion-weighted imaging without coexisting midbrain ischemia. The etiology of infarct was determined to be small vessel disease after extensive investigation. CONCLUSIONS: This report suggests a possible role of the thalamus as a vertical gaze control center. Clinicoradiological studies are needed to further define the role of the thalamus in vertical gaze control. PMID- 22040523 TI - Comparison of standardised dietary folate intake across ten countries participating in the European Prospective Investigation into Cancer and Nutrition. AB - Folate plays an important role in the synthesis and methylation of DNA as a cofactor in one-carbon metabolism. Inadequate folate intake has been linked to adverse health events. However, comparable information on dietary folate intake across European countries has never been reported. The objective of the present study was to describe the dietary folate intake and its food sources in ten countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cross-sectional analysis was conducted in 36 034 participants (aged 35-74 years) who completed a single 24 h dietary recall using a computerised interview software program, EPIC-Soft(r) (International Agency for Research on Cancer, Lyon). Dietary folate intake was estimated using the standardised EPIC Nutrient DataBase, adjusted for age, energy intake, weight and height and weighted by season and day of recall. Adjusted mean dietary folate intake in most centres ranged from 250 to 350 MUg/d in men and 200 to 300 MUg/d in women. Folate intake tended to be lower among current smokers and heavier alcohol drinkers and to increase with educational level, especially in women. Supplement users (any types) were likely to report higher dietary folate intake in most centres. Vegetables, cereals and fruits, nuts and seeds were the main contributors to folate intake. Nonetheless, the type and pattern of consumption of these main food items varied across the centres. These first comparisons of standardised dietary folate intakes across different European populations show moderate regional differences (except the UK health conscious group), and variation by sex, educational level, smoking and alcohol-drinking status, and supplement use. PMID- 22040524 TI - Size-dependent electron transfer from PbSe quantum dots to SnO2 monitored by picosecond Terahertz spectroscopy. AB - We report the direct and unambiguous determination of electron transfer rates and efficiencies from PbSe quantum dots (QDs) to mesoporous SnO2 films. We monitor the time-dependent electron density within the oxide with picosecond time resolution using Terahertz spectroscopy, following optical excitation of the QDs using a femtosecond laser pulse. QD-oxide electron transfer occurs with efficiencies of ~2% in our samples under 800 nm pumping with a marked dependence on QD size, ranging from ~100 ps injection times for the smallest, ~2 nm diameter QDs, to ~1 ns time scale for ~7 nm QDs. The size-dependent electron transfer rates are modeled within the framework of Marcus theory and the implications of the results for device design are discussed. PMID- 22040525 TI - Effects of non-fermented and fermented soybean milk intake on faecal microbiota and faecal metabolites in humans. AB - The effects of non-fermented soybean milk (NFSM) and fermented soybean milk (FSM) intake on the faecal microbiota and metabolic activities in 10 healthy volunteers were investigated. Soybean oligosaccharides, raffinose and stachyose were utilized by bifidobacteria except for Bifidobacterium bifidum, but most strains of Escherichia coli and Clostridium perfringens could not use them. During the dietary administration of FSM, the number of bifidobacteria and lactobacilli in the faeces increased (p < 0.05), and clostridia decreased (p < 0.05). Moreover, the concentrations of faecal sulphide were decreased (p < 0.01) in the intake of FSM. During the dietary administration of NFSM, the number of bifidobacteria tended to increase. These results indicate that the consumption of soybean milk, especially FSM, is related to improvement of the intestinal environment. PMID- 22040526 TI - Patient expectations of 'effectiveness' in health care: an example from medical herbalism. AB - AIMS AND OBJECTIVES: The study explored people's experiences of medical herbalism, with the aim of enhancing understanding about the use of herbalism in the context of contemporary UK health care. BACKGROUND: The popularity and use of complementary and alternative medicine in westernised societies is now well documented, and medical herbalism, in particular, is enjoying a particularly strong revival of interest. Despite this, the reasons for its sustained popularity remain unclear. DESIGN: The study was underpinned by Gadamerian hermeneutic phenomenology. METHOD: Nineteen adult clients of medical herbalists were interviewed about their experiences. The processes of data collection and data analysis were informed predominantly by van Manen's phenomenological framework and by Kvale's framework for interview-based studies. RESULTS: Herbalism more closely met participants' expectations of effective health care. The themes 'dealing with illness causation', 'patient-practitioner collaboration' and 'provision of authentic evidence' were fundamental to achieving effectiveness but were perceived as more easily attainable in the context of medical herbalism. CONCLUSIONS: Health care is more likely to meet the expectations of patients when its purposes, methods and goals are negotiated and made explicit, from the perspectives of both patient and health care professional. Medical herbalism has the potential to contribute usefully to participants' healthcare, especially when used selectively and in conjunction with conventional health care. RELEVANCE TO CLINICAL PRACTICE: The continued popularity of complementary and alternative medicine amongst the general public makes its acknowledgement in conventional health care more important than ever. In the context of the integrative health movement, it is therefore essential that health care professionals develop their understanding about patient practices and preferences, if a responsive health care system is to be maintained. Nurses are in a prime position to influence the knowledge base and future direction of integrative health care, especially in relation to the patient perspective. PMID- 22040527 TI - Color stability of resins and nylon as denture base material in beverages. AB - PURPOSE: Staining of prosthodontic materials may result in patient dissatisfaction and additional expense for replacement. This study aimed to determine the color stability of two heat-cured denture base acrylic (Lucitone 550, Vipi Cril) and one nylon denture base resin (Transflex) after immersion in beverages. MATERIALS AND METHODS: Forty disks of each resin (20.0-mm diameter, 3.0-mm thick) were prepared and stored in distilled water for 24 hours at 37 degrees C. During that time (T(0) ), the color of all specimens was spectrophotometrically measured. Each specimen was immersed in coffee, cola, red wine, and distilled water as a means of control. After 15-day (T(1) ) and 30-day (T(2) ) periods of immersion, the color of the specimens was measured again. The CIE (Commission Internationale de L' Eclairage) L*a*b* system was used to determine mean DeltaE (color changes) values for each material and compared statistically with two-way ANOVA and Bonferroni intervals at 0.95. RESULTS: In DeltaET(0) T(1) and DeltaET(0) T(2) the most severe staining was apparent with red wine (p < 0.001), followed by coffee (p < 0.01), when compared to the specimens stored in distilled water. Transflex also showed significant color change after immersion in cola (p < 0.01). In DeltaET(1) T(2) only red wine promoted significant staining of all resins (p < 0.0001). CONCLUSION: Chromatic changes were exhibited by specimens immersed in red wine, followed by coffee. For Transflex, cola also promoted color changes. The values of color changes converted to National Bureau of Standard units showed them to be perceivable to the human eye. PMID- 22040528 TI - Experience of an information aid for newly diagnosed multiple sclerosis patients: a qualitative study on the SIMS-Trial. AB - BACKGROUND: The SIMS-Trial (ISRCTN81072971) proved the effectiveness, in terms of patient's knowledge and care satisfaction, of an add-on information aid (personal interview with a physician using a navigable CD and take-home booklet) in 120 newly diagnosed patients with multiple sclerosis (MS) from five Italian centres. OBJECTIVE: To scrutinize the experience of SIMS-Trial participants in order to gain better understanding of the effectiveness of the information aid and its components. DESIGN: We performed (i) nine individual semi-structured interviews with a purposeful sample of SIMS-Trial patients who received the information aid, (ii) focus group meeting (FGM) with the physicians who conducted the personal interview, and (iii) FGM with patients' caring neurologists. RESULTS: Patients' experience with the information aid was positive as it enhanced their understanding of their disease, being viewed as a guided tour of their medical condition. The physicians who conducted the personal interviews were also positive in their overall evaluation but noted an initial difficulty in using the CD. The caring neurologists had limited direct experience of the aid, and their views were confined to utility of the information aid in general. All participants considered the combination of personal interview, CD navigation and take-home booklet essential, but urged a more flexible scheduling of the personal interview. It also emerged that some content required revision and that the aid was unsuitable for patients with primary progressive MS. CONCLUSIONS: The results of the study further support the value of the aid and also provide important indications for improving it and refining indications for use. PMID- 22040529 TI - Bacterial aetiology of diarrhoeal diseases and antimicrobial resistance in Dhaka, Bangladesh, 2005-2008. AB - Infectious diarrhoea caused by bacterial pathogens contributes to the high level of mortality in developing countries like Bangladesh. Following standard bacteriological procedures, a total of 14 428 bacterial pathogens were isolated from 56 132 stool samples and rectal swabs collected from diarrhoeal patients between 2005 and 2008. The rate of isolation and antimicrobial susceptibility data were retrospectively analysed for these isolates and among them Vibrio spp. (42.9%) were the most predominant, followed by Shigella spp. (20.3%), Aeromonas spp. (12.8%) and Salmonella spp. (6.4%). A decreasing trend in isolation of Vibrio spp. (P<0.001) and Salmonella spp. (P<0.001) was observed. While Vibrio cholerae isolates remained susceptible to ciprofloxacin, an increase in resistance was observed in Campylobacter spp. and Shigella flexneri. Variations in susceptibility to other tested antibiotics were observed among the isolated pathogens. Access to this current data will help in understanding the local burden of diarrhoeal disease and contribute to better design of prevention programmes. PMID- 22040530 TI - Does ampicillin-sulbactam cause false positivity of (1,3)-beta-D-glucan assay? A prospective evaluation of 15 patients without invasive fungal infections. AB - The purpose of this study was to investigate the interaction between intravenous ampicillin-sulbactam treatment and (1,3)-beta-D-glucan (BDG) assay. Fifteen patients with a median age of 60 (16-81) without known risk factors for invasive fungal infections who received a daily dose of 3*2g ampicillin-sulbactam monotherapy from different batches were included in the study. Thirteen patients had soft tissue infections. The 5 of 13 patients who went under surgery had surgical dressings. Serum samples were obtained both before and after antibiotic infusion on the first, third, seventh and tenth days of an ampicillin-sulbactam treatment course. BDG was assayed using the Fungitell kit (Associates of Cape Cod, East Falmouth, MA, USA) according to manufacturers' specifications. All serum samples were also tested for galactomannan (GM) antigenemia by Platelia Aspergillus ELISA (Bio-Rad Laboratories, Marnes-la-Coquette, France). A total of 37 of 117 serum samples were positive for BDG at a threshold of 80pg ml(-1) . Seven of 37 BDG positive serum samples had a GM index >=0.5. When a cutoff value of >=0.5 was used for GM positivity, 16 (13.3%) serum samples were positive. For a cutoff value of >=0.7, eight (6.6%) serum samples were positive. There were no statistically significant differences in the median BDG levels (P=0.47) or median GM indices (P =0.28) of the various sampling times. None of the SAM vials tested positive for BDG or GM. After ruling out fungal infections and all known potential causes of false BDG positivity, environmental contamination remained possible cause of BDG reactivity. We did not observe any significant association of ampicillin-sulbactam administration and positive assays for BDG or GM. PMID- 22040531 TI - [Travelers with Chikungunya infection: a threat for Europe]. PMID- 22040532 TI - Over-the-counter beta2-agonist purchase versus script: a cross-sectional study. AB - BACKGROUND: Purchase of short-acting beta(2)-agonist (SABA), but not anti inflammatory asthma medication, is permitted in Australia without a doctor's prescription. This has been associated with worse asthma outcomes. We sought to compare the asthma outcomes between those purchasing SABA with and without a doctor's prescription. METHODS: DESIGN: Cross-sectional study, using stratified randomisation of pharmacies. SETTING: 43 pharmacies in Victoria, Australia. PARTICIPANTS: Up to 10 consecutive adults purchasing beta(2)-agonists were recruited from each pharmacy, with 316 adults in total. OUTCOME MEASURES: Participants underwent spirometry and questionnaires on respiratory health, asthma control, Quality of Life and medication adherence. Asthma severity was determined by GINA medication step. Regression analyses were performed that allowed for clustering by pharmacy. RESULTS: Of 316 individuals recruited (65% participation rate), 191 (60%) purchased a beta(2)-agonist with a prescription. Purchase of SABA without prescription was not associated with worse asthma outcomes or lung function. Mean (+/-SD) asthma control score (ACQ) was 1.65 +/- 1.03; only 63 (20%) had well-controlled asthma (ACQ < 0.75). Anti-inflammatory asthma medication was owned by 188 (60%) of participants, of whom 157 (83%) reported using this in the last 7 days. There was no correlation between medication adherence scores and asthma control. Forty-seven participants (15%) had an FEV(1) below 80% predicted and did not own an anti-inflammatory asthma medication. CONCLUSION: Purchase of SABA without prescription was not associated with worse asthma outcomes in Australia. Although many patients reported symptoms of asthma, this did not appear to be associated with reported adherence to anti inflammatory asthma medication. PMID- 22040533 TI - Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD. AB - BACKGROUND: Combining maintenance medications with different mechanisms of action may improve outcomes in COPD. In this study we evaluated the efficacy and safety of fluticasone/salmeterol (FSC) (250/50 mcg twice daily) when added to tiotropium (18 mcg once daily) (TIO) in subjects with symptomatic moderate to severe COPD. METHODS: This was a 24-week, randomized, double-blind, parallel group, multi center study. Subjects 40 years or older with cigarette smoking history >=10 pack years and with the diagnosis of COPD and post-bronchodilator FEV(1) >=40 to <= 80% of predicted normal and FEV(1)/FVC of <=0.70 were enrolled. Following a 4 week treatment with open-label TIO 18 mcg once daily, subjects were randomized in a double-blind fashion to either the addition of FSC 250/50 DISKUS twice daily or matching placebo. The primary efficacy endpoint was AM pre-dose FEV(1) and secondary endpoints included other measures of lung function, rescue albuterol use, health status and exacerbations. RESULTS: The addition of FSC to TIO significantly improved lung function indices including AM pre-dose FEV(1), 2 h post-dose FEV(1), AM pre-dose FVC, 2 h post-dose FVC and AM pre-dose IC compared with TIO alone. Furthermore, this combination was superior to TIO alone in reducing rescue albuterol use. However, there were no significant differences between the treatment groups in health status or COPD exacerbations. The incidence of adverse events was similar in both groups. CONCLUSIONS: The addition of FSC to subjects with COPD treated with TIO significantly improves lung function without increasing the risk of adverse events. NCT00784550. PMID- 22040535 TI - Self-images and related autobiographical memories in schizophrenia. AB - Schizophrenia is a severe mental illness, which affects sense of identity. While the ability to have a coherent vision of the self (i.e., self-images) relies partly on its reciprocal relationships with autobiographical memories, little is known about how memories ground "self-images" in schizophrenia. Twenty-five patients with schizophrenia and 25 controls were asked to give six autobiographical memories related to four self-statements they considered essential for defining their identity. Results showed that patients' self-images were more passive than those of controls. Autobiographical memories underlying self-images were less thematically linked to these self-images in patients. We also found evidence of a weakened sense of self and a deficient organization of autobiographical memories grounding the self in schizophrenia. These abnormalities may account for the poor cohesiveness of the self in schizophrenia. PMID- 22040534 TI - PPARdelta regulates satellite cell proliferation and skeletal muscle regeneration. AB - Peroxisome proliferator-activated receptors (PPARs) are a class of nuclear receptors that play important roles in development and energy metabolism. Whereas PPARdelta has been shown to regulate mitochondrial biosynthesis and slow-muscle fiber types, its function in skeletal muscle progenitors (satellite cells) is unknown. Since constitutive mutation of Ppardelta leads to embryonic lethality, we sought to address this question by conditional knockout (cKO) of Ppardelta using Myf5-Cre/Ppardeltaflox/flox alleles to ablate PPARdelta in myogenic progenitor cells. Although Ppardelta-cKO mice were born normally and initially displayed no difference in body weight, muscle size or muscle composition, they later developed metabolic syndrome, which manifested as increased body weight and reduced response to glucose challenge at age nine months. Ppardelta-cKO mice had 40% fewer satellite cells than their wild-type littermates, and these satellite cells exhibited reduced growth kinetics and proliferation in vitro. Furthermore, regeneration of Ppardelta-cKO muscles was impaired after cardiotoxin-induced injury. Gene expression analysis showed reduced expression of the Forkhead box class O transcription factor 1 (FoxO1) gene in Ppardelta-cKO muscles under both quiescent and regenerating conditions, suggesting that PPARdelta acts through FoxO1 in regulating muscle progenitor cells. These results support a function of PPARdelta in regulating skeletal muscle metabolism and insulin sensitivity, and they establish a novel role of PPARdelta in muscle progenitor cells and postnatal muscle regeneration. PMID- 22040536 TI - Strategic consideration on treatment of multiple myeloma. PMID- 22040537 TI - Different dose combinations of bortezomib and dexamethasone in the treatment of relapsed or refractory myeloma: an open-label, observational, multi-center study in China. AB - BACKGROUND: Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma (RRMM), the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China. METHODS: A total of 168 patients with relapsed multiple myeloma (MM) who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m(2) of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose (group 1); 66 patients received less than 1.3 mg/m(2) (0.7 - 1.0 mg/m(2)) of bortezomib and dexamethasone 20 mg on the same schedule (group 2); 37 patients received 1.3 mg/m(2)2 of bortezomib and dexamethasone 40 mg (group 3) and 45 patients received less than 1.3 mg/m(2) (0.7 - 1.0 mg/m(2)) of bortezomib and dexamethasone 40 mg (group 4). The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. RESULTS: The median age of groups 1 to 4 was 61, 62, 56, and 60 years, respectively. Most patients were in stages II/III of MM and the most common subtype was IgG. The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2% (13/18), 73.8% (48/65), 78.8% (26/33) and 78.0% (32/41) (P = 0.91), including a complete response rate of 22.2% (4/18), 20.0% (13/65), 33.3% (11/33) and 29.3% (12/41) (P = 0.67), respectively. There was no statistical significance in time to progression and overall survival among these 4 groups (P > 0.05). The most commonly adverse events of any grade in the entire 4 groups were fatigue, gastrointestinal effects, peripheral neuropathy and thrombocytopenia, and there was no significance in the number of adverse events among the 4 groups (P > 0.05) except that peripheral neuropathy was reported more frequently in group 3 (36.3%) than in group 2 (13.8%, P < 0.05) and group 4 (14.6%, P < 0.05). CONCLUSIONS: The combination of bortezomib and dexamethasone was associated with high responses in Chinese RRMM patients. No significant differences of efficacy were detected in different dose combinations of bortezomib and dexamethasone. Moreover, low dose of bortezomib reduced the incidence of peripheral neuropathy without affecting outcome in the treatment of patients with RRMM in China. PMID- 22040538 TI - Clinical effects of autologous stem cell transplantation as consolidation treatment in 70 multiple myeloma patients: a case-controlled study. AB - BACKGROUND: Autologous stem cell transplantation (ASCT) is a part of the standard induction therapy of multiple myeloma (MM). This case-controlled clinical trial aimed to further evaluate the therapeutic effects of ASCT as a consolidation therapy for MM and discuss factors influencing the prognosis. METHODS: Clinical data of 70 patients diagnosed as MM who received ASCT as a consolidation therapy in our hospital between October 1998 and August 2010 were analyzed retrospectively (ASCT group). Other 70 MM patients receiving routine chemotherapy without ASCT (non-ASCT group) during the same period were used as controls. Differences in the degree and duration of remission, progression-free survival (PFS) and overall survival (OS) were compared to explore factors that may influence the prognosis. RESULTS: The median follow-up period was 38 months (range 1 - 128 months). The complete response (CR) rate of ASCT group increased from 27.1% (19/70) before ASCT to 51.4% (36/70) after ASCT. The median PFS of ASCT group was significantly higher than non-ASCT group (45 months vs. 25 months, P < 0.001). The median OS of ASCT group was also significantly higher (55 months vs. 30 months, P = 0.016). Single-factor analysis showed that International Staging System (ISS) stage, very good partial response (VGPR) or better outcome were significantly correlated with PFS and OS (P < 0.001). Multi-factor analysis showed that whether or not VGPR or better outcome was achieved were independent factors influencing the disease prognosis. CONCLUSION: Used as a consolidation therapy, ASCT can achieve better responses and higher OS and PFS of MM patients. PMID- 22040539 TI - Clinical significance of chromosomal abnormalities detected by interphase fluorescence in situ hybridization in newly diagnosed multiple myeloma patients. AB - BACKGROUND: Chromosome 13q14 deletion (del13q14), chromosome 1q21 gain (amp1q21) and chromosome 17p13 deletion (del17p13) are the most frequent chromosomal aberrations in multiple myeloma (MM). They play an important role in prognosis. The aim of this study was to investigate the clinical significance of the chromosomal changes in Chinese MM patients. METHODS: Interphase fluorescence in situ hybridization (FISH) on bone marrow (BM) cells was performed in 72 enrolled MM patients. Relationships between chromosomal abnormalities and clinical features, response to therapies and prognosis were analyzed. RESULTS: As a result of interphase FISH, 77.8% (56/72) patients had chromosome changes. The incidences of each probe were RB1 51.4% (37/72), D13S319 47.2% (34/72), 1q21 45.8% (33/72) and p53 22.2% (12/72). Osteolytic lesion, BM plasma cells index, serum calcium and serum M component were significantly correlated to del13q14. BM plasma cells and hemoglobin were correlated to amp1q21. Serum lactate dehydrogenase (LDH) was correlated with del17p13. Patients with del13q14 treated with bortezomib had a notably higher overall response rate than the patients treated with traditional chemotherapies (93% vs. 65%, P = 0.048). Patients carrying amp1q21 or/and del17p13 did not achieve satisfactory response to bortezomib. The median progression-free survival (PFS) for patients with amp1q21 was 5 months and patients without amp1q21 got 9-month PFS (P = 0.001). The median PFS for patients with del13q14 was 5 months (vs. 8 months, P = 0.026). The median PFS for patients with del17p13 was 3 months (vs. 8 months, P = 0.002). Patients with beta(2) microglobulin > 5.5 mg/L also had a worse outcome, whose median PFS was 5 months (vs. 8 months, P = 0.016). CONCLUSIONS: The prevalence of chromosomal abnormalities of MM patients was similar in Chinese and Caucasian people. Genetic changes were associated with patients' responses to therapies and prognosis. PMID- 22040540 TI - Use of arterial conduit for arterial revascularization during liver and multivisceral transplantation. AB - BACKGROUND: At present, revascularization is still one of the most critical technologies in orthotopic liver transplantation (OLT). Hepatic artery (HA) variations occur frequently in both donors and recipients. Moreover, there are always some pathological changes in the recipient hepatic artery. If handled improperly, it may cause complications after anastomosis. Therefore, arterial conduit could be used in primary OLT, re-OLT and multiple-OLT. This study aimed to investigate the indications, methods and techniques with usage of arterial conduit for HA revascularization during adult OLT. METHODS: We reviewed 1200 patients of consecutive OLTs performed during 2000 - 2009 in the First Affiliated Hospital of Sun Yat-sen University. Of these patients, 48 recipients with artery variations received HA revascularization with usage of arterial conduit and special postoperative managements. The indications, methods, techniques, and the managements of postoperative complications in adult OLT with usage of arterial conduit for HA revascularization were analyzed. RESULTS: In 48 cases with artery bypass, the arterial conduit were anastomosed between donor hepatic artery and recipient infrarenal aorta (n = 32), between donor hepatic artery and recipient suprarenal aorta (n = 10), and between donor upper abdominal organ cluster artery and recipient suprarenal aorta (n = 6). The technique was applied in 4% (48/1200 cases) of the whole OLTs performed in the same period, and the patency rate of the conduits was 100%. Forty patients (83.3%) survived, and the average survival time was 3.9 years. Eight patients (16.7%) died (all due to tumor recurrence), while the average survival time was 1.2 years. All these patients have not experienced artery-related complications in their survival time. CONCLUSIONS: When recipient HA has variations or pathological changes in OLT, the donor artery should be anastomosed to recipient abdominal aorta with an arterial conduit to achieve satisfactory outcomes. For arterial anastomosis can not be routinely performed, donor iliac artery as a conduit to be anastomosed with the recipient abdominal aorta is safe and effective. PMID- 22040541 TI - Simultaneous laparoscopic excision for rectal carcinoma and synchronous hepatic metastasis. AB - BACKGROUND: Rectal carcinoma patients are often accompanied by hepatic metastasis. The aim of this study was to evaluate the therapeutic efficacy of simultaneous laparoscopic excision for rectal carcinoma with synchronous hepatic metastasis. METHODS: A total of 41 patients with rectal carcinoma and synchronous hepatic metastasis detected by CT scan were included in this study. Among them, 23 patients underwent laparoscopic surgery and 18 patients underwent traditional open surgery to simultaneously remove the rectal tumor and hepatic metastasis lesions. All patients received postoperative adjuvant chemotherapy. All the patients were followed up from 36 to 72 months (mean 45.3 months). RESULTS: All the operations were performed successfully and no patient was turned to open surgery in laparoscopic group. The mean blood loss, the mean postoperative hospital stay, the mean blood transfusion and the mean intestinal functional recovery time showed a significant difference between the two groups (P < 0.05). The 1-, 3- and 5-year survival rates were 82.6%, 43.5% and 8.6% in the laparoscopic group, without significant difference compared with the open group (77.8%, 38.9% and 0) (P > 0.05). CONCLUSIONS: Simultaneous laparoscopic excision for rectal carcinoma and synchronous hepatic metastasis is safe and effective with similar survival achieved by the traditional open abdominal surgery. PMID- 22040542 TI - Therapeutic effects of endoscopic therapy combined with enteral nutrition on acute severe biliary pancreatitis. AB - BACKGROUND: Acute severe biliary pancreatitis (ASBP) is a severe and fatal disease, and the expenditure is huge and therapeutic effects are still not satisfactory. This study aimed to improve the therapeutic effects and reduce the expenditure of ASBP treatment. METHODS: One hundred and five patients diagnosed with ASBP were referred to our department from January 2004 to July 2009. Diagnosis was based on the 2007 criteria of the Chinese Society of Surgery. Patients were divided into two groups; the E group: 50 patients who underwent endoscopic retrograde choledochopancreatography (ERCP) + endoscopic sphincterotomy (EST) + endoscopic lithotripsy basket (ESR) + endoscopic retrograde biliary drainage (ERBD) and enteral nutrition (EN), and the R group: 55 patients who underwent traditional treatment without ERCP. Subsequently, subjective symptoms, signs, biochemical analysis, serum endotoxin, tumor necrosis factor a, grades by computed tomography (CT), cost of hospitalization and length of stay were compared between the two groups. RESULTS: All enrolled patients complied well with all therapeutic regimens. Endoscopic therapy that combined EN could significantly improve symptoms, clinical signs, laboratory values, tumor necrosis factor a and endotoxin while significantly reducing hospital expenditure and length of hospital stay. The experimental findings revealed that there were obvious advantages in the E group compared with the R group. CONCLUSIONS: Endoscopic therapy combined with EN is an effective, safe and economic therapeutic regimen of ASBP. PMID- 22040543 TI - Phase II clinical study on the modified DCF regimen for treatment of advanced gastric carcinoma. AB - BACKGROUND: A phase III trial involving docetaxel, cisplatin, and fluorouracil (DCF) in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but with a high rate of hematologic toxicity. To reduce toxicity while maintaining the efficacy of DCF, we reduced the doses of docetaxel (D) and cis-platinum (CDDP), and administered 5 fluorouracil (5-FU) via a continuous intravenous (CIV) infusion. METHODS: Chemotherapy-naive patients with gastric adenocarcinomas received D (60 mg/m(2) 1 hour on day 1), CDDP (30 mg/m(2) on days 1 and 2), and 5-FU (1500 mg*m(-2)*24 h( 1) CIV on days 1 and 8 every 3 weeks). The primary endpoint was the response rate. RESULTS: Fourteen patients were enrolled. Based on the efficacy evaluation following at least 2 cycles of treatment, there was 7.1% complete remission (CR), 71% partial remission (PR), 14% stable disease (NC/SD), and 7.1% progressive disease (PD). The median survival time was 13 months. Nine patients (64%) had grade III-IV neutropenia, and 4 patients (29%) had grade IV neutropenia, among whom 1 had grade IV neutropenia with grade III nausea and vomiting. CONCLUSION: The modified DCF regimen is highly active and has a favorable toxicity profile in Chinese patients with gastric cancer. PMID- 22040544 TI - Management with the insufficient proximal landing zone for endovascular repair in aortic dissection. AB - BACKGROUND: Sufficient length of the proximal landing zone (PLZ) is the key for a successful thoracic endovascular aortic repair (TEVAR) of an aortic lesion. The aim of this research was to investigate the safety, feasibility, efficacy, and problems of endovascular repair for aortic dissection with insufficient PLZ. METHODS: The clinical data between August 2005 and February 2010 from patients with insufficient PLZ for endovascular repair of aortic dissection were retrospectively reviewed. According to the classification proposed by Ishimaru, aortic zone 0 was involved in 3 cases, zone 1 in 10 cases, and zone 2 in 11 cases. A hybrid surgical procedure of supraortic debranching and revascularization, directly coverage the orifice of left subclavian artery, or a left common carotid artery chimney graft technique were performed to obtain an adequate proximal aortic landing zone. RESULTS: There was no significant difference in risk factors and diameter of the PLZ between Zone 0, Zone 1, and Zone 2. But the length of the PLZ was significantly different in the three groups (P < 0.01). There was no significant difference in technical and clinical success rate between the groups. CONCLUSIONS: The procedure for extending an insufficient PLZ for endovascular repair for aortic arch pathology is feasible and relatively safe. The applicability of TEVAR in such aortic disorders may be expanded. PMID- 22040545 TI - Clinical analysis of vascular anomalies: a hospital-based retrospective study of 592 patients in southeast China. AB - BACKGROUND: Vascular anomalies are common and multidisciplinary involved diseases. The greatest impediment to their treatment in the past was their confusing terminology and clinical heterogeneities. This hospital-based retrospective study assessed some clinical characteristics, diagnosis, therapies and outcomes of patients with vascular anomalies in southeast China. METHODS: A total of 592 vascular anomalies patients (patients with intracranial tissues or viscera involved were excluded), admitted to the First Affiliated Hospital of Sun Yat-sen University from January 2006 to September 2009, were enrolled in the study. Data for clinical characteristics, diagnosis, therapies and outcomes were collected and analyzed. RESULTS: Of the 592 patients, the male:female ratios in the vascular tumor group (n = 187) and the vascular malformation group (n = 405) were 1:1.49 and 1:1.06 respectively, with no significant difference between them. The mean onset age of the vascular tumor group was significantly younger than that of the vascular malformation group (p < 0.001). The head and neck were the most commonly (31.4%) involved areas in vascular anomalies. A total of 23.8% of the patients with vascular anomalies had definite symptoms caused by the vascular lesions. In the vascular tumor group, 94.1% of them were infantile hemangiomas. Venous malformation was the most common (41.0%) subtype of vascular malformations. Surgical therapy was undertaken in 94.2% of the patients with vascular anomalies. Of the 519 patients available for the 16 - 58 month follow up, 322 patients (62.0%) were cured, 108 patients (20.8%) were markedly improved, 57 patients (11.0%) were partially improved, and 32 patients (6.2%) were uncured. CONCLUSIONS: Vascular anomalies are clinically heterogeneous. While the outcome is generally favorable, further effort should be made to determine the appropriate terminology and management. PMID- 22040546 TI - Aesthetic fingertip reconstruction with partial second toe transfer. AB - BACKGROUND: Fingertip defect significantly affects the appearance of the hand. The aim of this research was to evaluate the clinical effect of aesthetic fingertip reconstruction with partial second toe transfer. METHODS: Between July 2005 and December 2008, 17 patients underwent aesthetic fingertip reconstruction with partial second toe transfer. The mean size of fingertip defects was 0.7 cm (ranging from 0.5 - 1.1 cm). Anastomosis was performed between one dominant plantar digital artery and one proper digital artery, between two dorsal digital veins of the toe and two dorsal digital veins of the finger, respectively, for the reconstruction of blood supply to the reconstructed finger. Two plantar digital nerves of the toe were then sutured to two proper digital nerves of the finger for the restoration of fingertip sensation. RESULTS: All reconstructed fingers survived completely. The follow-up period ranged from 6 to 24 months, and the appearance of the reconstructed fingertip was similar to that of the normal fingertip. Two-point discrimination of the reconstructed fingertip was (7.8 +/- 1.3) mm. The recovered pinch strength of the reconstructed finger was about (89.0 +/- 5.1)% of that of the normal finger. Donor site healed well without complications. CONCLUSIONS: Partial second toe transfer is an ideal aesthetic reconstruction method for fingertip defects; it can not only achieve a satisfactory appearance of the fingertip, but can also obtain excellent sensory and motor functions. PMID- 22040547 TI - Off-pump sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system. AB - BACKGROUND: Off-pump coronary artery bypass surgery (OPCAB) has been widely applied in recent years as a less invasive method of myocardial revascularization. This study evaluated the sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system during OPCAB. METHODS: From April 2004 to August 2010, patients with diffuse right coronary lesions were studied retrospectively and divided into two groups. Group 1 included seventeen patients who underwent this surgery while group 2 included twenty-one patients without right coronary artery surgical therapy. All patients presented with symptoms of angina. Blood flow of bridged vessels was measured. The perioperative ventricular parameters including left ventricular ejection fraction and end diastolic diameter were compared. During follow-up, myocardial nuclide imaging and coronary angiography were carried out. RESULTS: Off-pump coronary artery bypass was performed with an average of 3.6 grafts per patient. Hospital mortality was zero. At the time of follow-up, the patients in group 1 recovered better than in group 2 (P < 0.05). In both groups, the mean New York Heart Association (NYHA) class and ejection fraction increased significantly (P < 0.001) and the mean left ventricular end-diastolic diameter decreased significantly (P < 0.05). Myocardial blood supply of inferior wall in group 1 was obviously improved by myocardial nuclide imaging. Coronary angiography for eight patients in group 1 verified that there was blood flow to myocardium in the arterialized vein. CONCLUSIONS: Sequential bilateral internal mammary artery grafting combined with selective arterialization of the coronary venous system can be performed during OPCAB. A postoperative improvement in the cardiac functions and the quality of life was documented, increasing our expectation for extensive application. PMID- 22040548 TI - Increased plasma C-reactive protein level predicts rapid progression of non target atherosclerotic lesions in patients with stable angina after stenting. AB - BACKGROUND: Although the role of C-reactive protein (CRP) in predicting rapid progression of atherosclerotic lesions has been intensively studied in unstable coronary artery disease, the data from patients with stable angina (SA) are largely absent. The present study evaluated a middle-size patient cohort who underwent percutaneous coronary intervention (PCI) with stent implantation and follow-up coronary angiography (CAG) and tested the hypothesis that increased plasma level of high-sensitive CRP would indicate rapid progression of de novo non-target coronary artery lesions in Chinese patients with SA. METHODS: The study population comprised of 311 consecutive patients with chronic SA who underwent coronary stent implantation on initial admission and angiographic follow-up ((8.5 +/- 1.2) months). Rapid angiographic progression of non-target lesion was angiographically assessed and the patients were classified into two groups according to whether the progression existed or not. The relation of plasma CRP levels to the progression of atherosclerosis was investigated. RESULTS: Baseline demographic, clinical, and angiographic data were similar in patients with and without progression. Rapid angiographic progression of non target lesions occurred in 136 patients (43.7%) at follow-up: 77 had a >= 10% diameter reduction of pre-existing stenosis >= 50%, 26 had a >= 30% diameter reduction of a pre-existing stenosis < 50%, 64 developed a new lesion >= 30% in a previously normal segment, and 4 had progression of a lesion to total occlusion. Progression of non-target lesions was not associated with target lesion restenosis formation. High-sensitive CRP levels were markedly higher in progression patients than in non-progression ones (1.60 (0.80 - 3.46) mg/L vs. 0.96 (0.55 - 1.87) mg/L, P < 0.001). Multivariate regression analysis showed that plasma CRP independently predicted rapid angiographic progression of non-target lesions (P = 0.001). High-sensitive CRP levels above 1.32 mg/L (the cutoff value) were associated with a 3.5-fold increase in the risk of developing rapid atherosclerotic progression (OR = 3.497, 95%CI 2.045 - 5.980). CONCLUSION: The data confirmed and extended previous studies that plasma CRP might independently predict non-target lesion progression in patients with SA after stent implantation. PMID- 22040549 TI - Reasons for the upsetting cholesterol level during the community investigation from residents, physicians, and social aspects: the China Cholesterol Education Program (CCEP). AB - BACKGROUND: The community medical center is the first barrier for lipid control. We aimed to survey the residents' cholesterol condition in the community, and pursue the reasons for the upsetting results from various aspects. METHODS: Residents and physicians were recruited from four community centers. Residents completed questionnaires and a physical examination as well as biochemical analysis. Physicians were also asked to complete a questionnaire, some of which were about basic knowledge of lipids. RESULTS: About 37.0% male and 48.1% female had elevated cholesterol levels. Residents' blood pressure (BP), fasting glucose (FG), body mass index (BMI), and waist circumference (WC) were positively associated with their low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Framingham risk scoring (FRS) was strongly related to cholesterol (P < 0.001 for LDL-C and TC). Residents' higher education grade was positively related to a normal cholesterol condition (P < 0.001), while personal income was negatively related to it. Rural residents had higher percent of population with normal cholesterol level (normal cholesterol rate) than their city counterpart (P < 0.001). Although physicians with college education had a much higher lipid knowledge level themselves, the physicians' factors had almost no relationship with the residents' cholesterol levels. CONCLUSIONS: Management of hypercholesterolemia should be an important component of health strategy in Beijing. Education is imperative for residents as well as for physicians. PMID- 22040550 TI - Three core techniques in surgery of neuroepithelial tumors in eloquent areas: awake anaesthesia, intraoperative direct electrical stimulation and ultrasonography. AB - BACKGROUND: The goal of surgery in the treatment of intrinsic cerebral tumors is to resect the maximum tumor volume, and to spare the eloquent areas. However, it is difficult to discover the eloquent areas intraoperatively due to individual anatomo-functional variability both for sensori-motor and language functions. Consequently, the surgery of intrinsic cerebral tumors frequently results in poor extent of resection or permanent postoperative deficits, or both, and remains a difficult problem for neurosurgeons. METHODS: From January 2003 to January 2010, 112 patients with neuroepithelial tumors in/close to the eloquent areas were operated on under awake anesthesia with the intraoperative direct electrical stimulation for functional mapping of the eloquent areas. The extent of the tumors was verified by intraoperative ultrasonography. The maximal resection of the tumors and minimal damage of the eloquent areas were the surgical goal of all patients. RESULTS: Totally 356 cortical sites in 99 patients were detected for motor response by intraoperative direct electrical stimulation, 50 sites in 16 patients for sensory, 72 sites in 48 patients for language. Sixty-six patients (58.9%) achieved total resection, 34 (30.4%) subtotal and 12 (10.7%) partial. Fifty-eight patients (51.8%) had no postoperative deficit, while 37 patients (33.0%) had transitory postoperative paralysis, 26 patients (23.2%) with transitory postoperative language disturbance and 3 patients (2.7%) with permanent neurological deficits. No patient complained of pain recollection following operation. CONCLUSIONS: Awake anesthesia, intraoperative direct electrical stimulation and ultrasonography are three core techniques for the resection of intrinsic cerebral tumors near the eloquent areas. This new concept allows an improvement in the quality of surgery for neuroepithelial tumors in/adjacent to eloquent areas. PMID- 22040551 TI - Increase of plasma IgE during treatment correlates with better outcome of patients with glioblastoma. AB - BACKGROUND: Previous studies have shown that glioma patients have lower blood IgE levels than controls. To evaluate its potential as a surrogate biomarker for glioma, we measured plasma IgE levels in glioma patients and healthy controls, and correlated them with clinicopathological factors and the patients' outcome. METHODS: We used enzyme-linked immunosorbant assay (ELISA) to determine the plasma IgE levels of 25 normal subjects and 252 glioma patients (85 patients with grade II glioma, 46 patients with grade III glioma, and 121 patients with glioblastoma). We also collected longitudinal plasma samples from glioblastoma patients and compared the plasma IgE levels before operation, one week after operation, in the middle of radiotherapy, after two cycles of chemotherapy, and after recurrence. The correlations between plasma IgE levels and the outcomes of the patients were determined. RESULTS: Plasma IgE levels were significantly lower in glioma patients (P = 0.004); patients with low-grade glioma have lower IgE levels than patients with high-grade glioma do (P = 0.029). In 24 patients with both preoperative plasma and two-cycle chemotherapy plasma samples, IgE levels increased after successful removal of the tumor (P = 0.021), and the increase correlated with the patients' survival (increase > 100 ng/ml vs. <= 100 ng/ml, 127.5 weeks vs. 62.3 weeks. P = 0.012, log-rank). Plasma IgE level increase of > 100 ng/ml has a specificity of 80% and a sensitivity of 78% to predict the patients' long survival (> 18 months). CONCLUSIONS: Our results suggest that plasma IgE level correlates with clinical and pathological factors in glioma patients. It has the potential to be a biomarker for glioma patients. PMID- 22040552 TI - Retraction: Prognostic analysis of transarterial chemoembolization combined with a traditional Chinese herbal medicine formula for treatment of unresectable hepatocellular carcinoma. PMID- 22040553 TI - Benefit of infusions with ibandronate treatment in children with osteogenesis imperfecta. AB - BACKGROUND: Osteogenesis imperfecta (OI) is a rare bone disease and its effective treatment is relatively deficient. We tried to assess the effects of new bisphosphonate, ibandronate on children with OI. METHODS: In this open-label, prospective, controlled study, 30 children with OI were enrolled. They received either infusions of ibandronate (2 mg) in every three months or oral calcitriol 0.25 ug daily for 24 months. All patients took 500 mg calcium plus 200 U vitamin D daily together. The endpoints were the change of annual new fracture rate (observed by case history and X ray films of spine), bone mineral density (BMD, measured by dual energy X-ray absortiometry), serum concentration of carboxy telopeptide cross-links of type I collagen (CTX, bone resorption marker) and alkaline phosphatase (ALP, bone formation marker) during the follow-up. RESULTS: After the cyclic infusions of ibandronate, the annual new fracture rate was significantly decreased from 1.9 to 0.13 time, obviously lower than that of calcitriol group, which decreased from 1.8 to 1.0 time after the treatment (P < 0.001). The significant increase of BMD at the lumbar spine, femoral neck, trochanter, total hip was found in the group of ibandronate by 59.0%, 42.0%, 47.5% and 36.6% in time dependent manner (compared with the baseline, P < 0.001). The increase of BMD in ibandronate group was greater than that of calcitriol group (P < 0.001). The concentrations of ALP and CTX were obviously decreased in ibandronate group, and the reduction of CTX was more significant than that of ALP (P < 0.001). The tolerance of the children to ibandronate was quite well. Mild fever and muscle pain were found in 9 cases within 1 - 3 days after the first infusion of ibandronate, which could relieve after 1 - 2 days without special management. CONCLUSIONS: The benefits of cyclic infusions of ibandronate to children with OI are significant because ibandronate could significantly reduce annual bone fracture rate, increase lumbar and hip BMD, preserve vertebral morphometry of patients through inhibition of bone resorption. PMID- 22040554 TI - Mutation analysis and prenatal diagnosis of EXT1 gene mutations in Chinese patients with multiple osteochondromas. AB - BACKGROUND: Multiple osteochondromas (MO), an inherited autosomal dominant disorder, is characterized by the presence of multiple exostoses on the long bones. MO is caused by mutations in the EXT1 or EXT2 genes which encode glycosyltransferases implicated in heparin sulfate biosynthesis. METHODS: In this study, efforts were made to identify the underlying disease-causing mutations in patients from two MO families in China. RESULTS: Two novel EXT1 gene mutations were identified and no mutation was found in EXT2 gene. The mutation c.497T > A in exon 1 of the EXT1 gene was cosegregated with the disease phenotype in family 1 and formed a stop codon at amino acid site 166. The fetus of the proband was diagnosed negative. In family 2, the mutation c.1430-1431delCC in exon 6 of the EXT1 gene would cause frameshift and introduce a premature stop codon after the reading frame being open for 42 amino acids. The fetus of this family inherited this mutation from the father. CONCLUSIONS: Mutation analysis of two MO families in this study demonstrates its further application in MO genetic counseling and prenatal diagnosis. PMID- 22040555 TI - Changes in serum levels of soluble osteoclast-associated receptor in human rheumatoid arthritis. AB - BACKGROUND: Osteoclast-associated receptor (OSCAR) is a member of the newly identified leukocyte receptor complex, and has recently been described as a key molecule in osteoclastogenesis. In this study, we measured the levels of soluble osteoclast-associated receptor (sOSCAR) in the serum of rheumatoid arthritis (RA) patients and healthy controls to examine whether sOSCAR may play a role in the process of inflammatory arthritis. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of sOSCAR in the serum of 40 healthy controls and 40 RA patients. RESULTS: The serum levels of sOSCAR were significantly lower in RA patients than in healthy controls, and were inversely associated with inflammatory activity. CONCLUSION: sOSCAR is decreased in patients with RA and reduced levels of the protein are associated with increased inflammatory response. PMID- 22040556 TI - Expression of aquaporin 8 and its relationship with melanosis coli. AB - BACKGROUND: The relationship between melanosis coli (MC) and aquaporin 8 (AQP8) has not yet been elucidated. The aim of this research was to investigate the relationship between the expression of AQP8 and the pathological mechanism of MC. METHODS: Expression of AQP8 was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) in 37 MC colon tissues and 13 control colon tissues. Global gene expression analysis was also used to identify differently expressed genes. Its relationship with MC was analyzed by SPSS 11.5 statistical software. RESULTS: The positive rate of AQP8 expression detected by immunohistochemistry in the MC group was 24.3% (9/37), significantly lower than the 69.2% (9/13) in the control group (P < 0.05). The relative expression level of AQP8 in MC group was 0.639 +/- 0.160, lower than 0.921 +/- 0.148 of controls (P < 0.05). Global gene expression analysis showed that AQP8 mRNA expression was downregulated in MC patients. CONCLUSIONS: The decreased AQP8 expression in MC patients indicates that chronic use of laxatives containing anthraquinone may cause reduced water absorption. The expression of AQP8 may be related to MC. PMID- 22040557 TI - Long-term intraocular pressure fluctuation of primary angle closure disease following laser peripheral iridotomy/iridoplasty. AB - BACKGROUND: Many studies indicated that short-term and long-term intraocular pressure (IOP) fluctuations in primary open angle glaucoma patients might lead to glaucomatous progression. However, seldom study has evaluated the long-term fluctuation of IOP in primary chronic angle closure diseases. The objective of this study was to investigate the long-term IOP fluctuation of primary angle closure diseases and its associations following laser peripheral iridotomy (LPI) with or without laser peripheral iridoplasty. METHODS: A total of 158 patients with primary angle closure suspect (PACS, n = 21), primary angle closure (PAC, n = 81) and primary angle closure glaucoma (PACG, n = 55) had been treated by LPI with or without laser peripheral iridoplasty and followed up for more than 12 months. IOP was measured with Goldman applanation tonometer. Multivariate linear regression with generalized estimating equation (GEE) regression models was used to evaluate the association of long-term IOP fluctuation (maximum IOP minus minimum IOP) with gender, age, baseline IOP, baseline peripheral anterior synechia (PAS), baseline vertical cup/disc ratio (VCDR), baseline mean deviation (MD), need for IOP-lowering medications. RESULTS: IOP fluctuation during follow up in PACS, PAC and PACG groups were (4.83 +/- 2.90), (5.67 +/- 3.35), and (9.40 +/- 7.14) mmHg, respectively. IOP fluctuation was strongly correlated with baseline IOP (r = 0.356, P < 0.001), PAS (r = 0.374, P < 0.001). IOP fluctuation was higher in patients with higher baseline IOP (0.18 mmHg per unit increase, 95%CI: 0.05 - 0.31 mmHg). CONCLUSIONS: Long-term IOP fluctuation in PACG group was larger than that in PACS or PAC group. Eyes with higher baseline IOP were observed to have larger long-term IOP fluctuation. PMID- 22040558 TI - Effect of periodontal treatment on glycosylated hemoglobin levels in elderly patients with periodontal disease and type 2 diabetes. AB - BACKGROUND: Periodontal disease is closely related to type 2 diabetes and is an important complication of diabetes. This study aimed to investigate the effect of periodontal treatment on levels of blood glucose (Glu) and glycosylated hemoglobin (HbA1c) among elderly patients with type 2 diabetes and periodontal disease. METHODS: A total of 107 elderly patients with type 2 diabetes and periodontal disease were selected and divided into two groups according to their HbA1c levels. Group A was a well-controlled diabetic group and group B was uncontrolled. Their probing depth (PD), attachment loss (AL), the value of Glu and HbA1c were analyzed before periodontal treatment and 4 months later. RESULTS: There was a significant difference in periodontal condition between groups A and B (P < 0.01). The periodontal condition for both groups was significantly (P < 0.01) improved after periodontal therapy. The effect of treatment in group A was more pronounced than group B, and the difference was significant (P < 0.01). After the periodontal treatment, Glu and HbA1c were reduced significantly in both groups (P < 0.05). CONCLUSIONS: Periodontal condition is related to the control of Glu level among elderly patients with type 2 diabetes and periodontal disease. Periodontal treatment can effectively reduce the level of Glu and HbA1c as well as improve the periodontal condition in elderly type-2 diabetes patients with periodontal disease. PMID- 22040559 TI - SLAM family predicting the initiation potential of human acute lymphoblastic leukemia in NOD/SCID mice. AB - BACKGROUND: The SLAM family recently has been reported to show an important biological role in lymphocyte development and immunological function, and it is efficient to highly purify hematopoietic stem cells using a simple combination of SLAM family members. To elucidate the presence of this family on acute lymphoblastic leukemia (ALL), as well as its relationship with the leukemia initiating potential, we analyzed the expression pattern of this family members on human ALL progenitor cells, combined with serial xenotransplantation assay. METHODS: Expression analysis was carried out by flow cytometry. We combined the expression pattern of human CD(150), CD(244) and CD(48) with serial xenotransplantation of B-ALL progenitor cells to indicate their relationship. RESULTS: CD(48) and CD(244) were expressed on most B-ALL progenitor cells, the percentage being (93.08 +/- 6.46)% and (63.37 +/- 29.31)%, respectively. Interestingly, the proportion of CD(150)(+) cells declined obviously in engrafted cases ((24.94 +/- 7.32)%) compared with non-engrafted cases ((77.54 +/- 5.93)%, P < 0.01), which indicated that only blast cells with low percentage of CD(150)(+) population were able to reconstitute leukemia into primary, secondary and tertiary NOD/SCID mice. CONCLUSIONS: SLAM family members are present on B-ALL progenitor cells and the leukemia-initiating potential of leukemic blasts is correlated negatively with the proportion of CD(150)(+) cells, the percentage of which can serve as a useful predictor for engraftment success of B-ALL to immune deficient mice. PMID- 22040560 TI - In vitro chondrogenesis of the goat bone marrow mesenchymal stem cells directed by chondrocytes in monolayer and 3-dimetional indirect co-culture system. AB - BACKGROUND: Cartilage injury has a very poor capacity for intrinsic regeneration. The cell-based treatment strategy for the cartilage repair using differentiated bone marrow mesenchymal stem cells (BMSCs) is, however, a promising approach to the chondral repair. This study was aimed to explore the chondrogenic potential of the goat BMSCs in the Transwell co-culture system and the poly-laetide-co glycolide (PLGA) scaffolds. METHODS: The BMSCs were isolated from the goat iliac crest while the chondrocytes were obtained from the goat's last costal cartilage. In the Transwell co-culture system, the BMSCs co-cultured with chondrocytes were designed as group A, whereas the goat's BMSCs induced with the chondrogenic medium were group B. Both groups A and B were the experimental groups, while group C that only contained BMSCs was the control group. In the PLGA scaffolds co culture system, BMSCs were seeded into the PLGA scaffolds, which were suspended in the 24-well plate, and the control group was established by presence or absence of chondrocytes at the bottom of the 24-well plate. Toluidine blue staining, Alcian blue staining, collagen II immunofluoresence, collagen II immunochemical staining, collagen I, collagen II, COL2a Q-PCR and osteopontin Q PCR were used to examine the chondrogenic conditions as well as the expressions of chondrogenic and osteogenic genes. RESULTS: Cells isolated from the aspirates of the goat bone marrow proliferated rapidly and gained characteristics of stem cells in Passage 4. However, the differentiations of chondrocytes were not apparent in Passage 3. The results from Toluidine blue staining, collagen II immunofluoresence and PCR showed the transformation of BMSCs to chondrocytes in the Transwell co-culture system and PLGA scaffolds. Although the cartilage gene expressions were upgraded in both chondrogenesis group and co-culture system, the osteopontin gene expression, which represents osteogenic level, was also up regulated. CONCLUSIONS: The Transwell co-culture system and the PLGA scaffolds co culture system can promote the chondrogenic differentiation of the goat's BMSCs, while up-regulated osteopontin gene expression in the Transwell co-culture system implies the osteogenic potential of BMSCs. PMID- 22040561 TI - A surface-modified biodegradable urethral scaffold seeded with urethral epithelial cells. AB - BACKGROUND: Efficient cell adhesion and proliferation is a central issue in cell based tissue engineering, which offers great promise for repair of urethral defects or strictures. This study evaluated the adhesion and growth of rabbit uroepithelium on a surface-modified three-dimensional poly-L-lactic acid (PLLA) scaffold. METHODS: Urethral mucosa were harvested from male New Zealand rabbits and the urothelium were dissociated and then cultured. Immunocytochemistry on cultured uroepithelium for pancytokeratin and uroplakin II and TE-7 confirmed pure populations. After in vitro proliferation, cells were seeded onto a surface modified urethral scaffold with non-knitted filaments. The morphology and viability of the cells were examined by immunohistochemical and fluorescence staining. Inverted and scanning microscopes were used to document cell growth and adhesion. RESULTS: Three to five days after primary culture, the uroepithelial cells gradually became confluent, assuming a cobblestone pattern. The filaments of the urethral scaffold had excellent biocompatibility and allowed growth of the uroepithelium, without affecting viability. The uroepithelial cells adhered to and grew well on the scaffold. After 3 - 7 days, the cells grew vigorously and meshes of the scaffold were full of uroepitheliums. CONCLUSIONS: The surface modified urethral scaffold with non-knitted filaments allows the growth of uroepithelium and can serve as a carrier for the tissue engineering of urethra. PMID- 22040562 TI - Over-expression of VEGF165 in the adipose tissue-derived stem cells via the lentiviral vector. AB - BACKGROUND: Many researchers studied the possibility of using stem cells as gene therapeutic vector. But few related reports on the adipose tissue-derived stem cells (ADSCs) are available. Therefore we intended to construct a lentiviral VEGF(165) expression vector and then infect the ADSCs to produce therapeutic seed cells. METHODS: EHS1001-68950485313912 clone was mutated by PCR method to produce consensus fragment of VEGF(165) transcript (NM_001025368). Lentivirus was enveloped with pGC-FU, pHelper 1.0 and pHelper 2.0 plasmids in 293T cells. And then the ADSCs (multiplicity of infection = 20) were transfected with the vectors after titer determination. Stable expression of VEGF(165) in ADSCs was confirmed by immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA) and Western blotting analysis. RESULTS: DNA sequencing and 293T transfection verified VEGF(165) was linked to the GFP fused vector. The virus titer is up to 2 * 10(8) determined by quantitative PCR. VEGF(165) transduced cells could show green fluorescence confirmed by immunofluorescence staining (almost 95%). ELISA analyses could detect out the density of VEGF was 850.86 - 1202.13 pg/ml (mean (923.00 +/- 31.22) pg/ml) in the supernatant of VEGF(165)-transduced cells but not detected in the GFP-transduced cells (P < 0.001) and the Western blotting analyses also confirmed VEGF(165) expression in VEGF(165)-transduced cells. CONCLUSIONS: The VEGF(165) over-expression ADSCs were obtained and may be used as a cell therapeutic tool and may be applied for vascular regeneration, especially in the treatment of erectile dysfunction. PMID- 22040563 TI - Fasudil inhibits platelet-derived growth factor-induced human pulmonary artery smooth muscle cell proliferation by up-regulation of p27kip1 via the ERK signal pathway. AB - BACKGROUND: RhoA/Rho kinase (ROCK) pathway is involved in pulmonary arterial hypertension (PAH) and pulmonary artery smooth muscle cell (PASMC) proliferation. Inhibition of ROCK has been proposed as a treatment for PAH. But the mechanism of RhoA/ROCK pathway and its downstream signaling in proliferation of human PASMCs is unclear. We investigated the effect of fasudil, a selective ROCK inhibitor, on platelet-derived growth factor (PDGF) induced human PASMC proliferation, and the possible association between RhoA/ROCK and extracellular signal-regulated kinase (ERK), p27(Kip1). METHODS: Human PASMCs were cultured with the stimulation of 10 ng/ml PDGF, and different concentrations of fasudil were added before the addition of mitogen. Cell viability and cell cycle were determined with MTT and flow cytometry respectively. ROCK activity, ERK activity and protein expression of proliferating cell nuclear angigen (PCNA) and p27(Kip1) were measured by immunoblotting. RESULTS: By MTT assay, PDGF significantly increased the OD value that represented human PASMC proliferation, and pretreatment with fasudil significantly reversed this effect in a dose-dependent manner. After PDGF stimulation, the percentage of cells in S phase increased dramatically from 15.6% to 24.3%, while the percentage in G(0)/G(1) phase was reduced from 80.6% to 59%. And pretreatment with fasudil reversed the cell cycle effect of PDGF significantly in a dose-dependent manner. PDGF markedly induced ROCK activity and ERK activity with a peak at 15 minutes, which were significantly inhibited by fasudil. In addition, fasudil significantly inhibited PDGF-induced PCNA expression and fasudil also upregulated p27(Kip1) expression in human PASMCs, which decreased after PDGF stimulation. CONCLUSION: RhoA/ROCK is vital for PDFG induced human PASMC proliferation, and fasudil effectively inhibited PDGF-induced human PASMC proliferation by up-regulation of p27(Kip1), which may be associated with inhibition of ERK activity. PMID- 22040564 TI - The effects of paeoniflorin monomer of a Chinese herb on cardiac ion channels. AB - BACKGROUND: Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels. METHODS: Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current (I(Ca-L)), inward rectifier potassium current (I(K1)), and transient outward potassium current (I(to1)) were studied in rat ventricular myocytes and sodium current (I(Na)), slow delayed rectifier current (I(Ks)), and HERG current (I(Kr)) were investigated in transfected human embryonic kidney 293 cells. RESULTS: One hundred umol/L paeoniflorin reduced the peak I(Ca-L) by 40.29% at the test potential of +10 mV (from (-9.78 +/- 0.52) pA/pF to (-5.84 +/- 0.89) pA/pF, n = 5, P = 0.028). The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were ( 11.22 +/- 0.27) mV vs. (-5.95 +/- 0.84) mV (n = 5, P = 0.007), respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred umol/L paeoniflorin completely inhibited the peak I(Na) and the effect was reversible. Moreover, paeoniflorin inhibited the I(K1) by 30.13% at the test potential of -100 mV (from -25.26 +/- 8.21) pA/pF to (-17.65 +/- 6.52) pA/pF, n = 6, P = 0.015) without effects on the reversal potential and the rectification property. By contrast, 100 umol/L paeoniflorin had no effects on I(to1), I(Ks) or I(Kr) channels. CONCLUSIONS: The study demonstrated that paeoniflorin blocked I(Ca-L), I(Na), and I(K1) without affecting I(to1), I(Ks), or I(Kr). The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential. PMID- 22040565 TI - Inactivation of mammalian target of rapamycin (mTOR) by rapamycin in a murine model of lipopolysaccharide-induced acute lung injury. AB - BACKGROUND: The mammalian target of rapamycin (mTOR) pathway, a key cellular signaling pathway associated with various cellular functions, has distinct roles in the inflammatory process. In this study, the mTOR inhibitor rapamycin (Rapa) was used to test whether inhibition of mTOR activation attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a murine model. METHODS: Mice pretreated with Rapa or vehicle were given LPS intratracheally. Local cell numbers and inflammatory cytokines present in the bronchoalveolar lavage fluid (BAL), wet-to-dry weight ratio, histopathology of the lungs, and survival were evaluated. RESULTS: The phosphorylation of S6, a major downstream target of mTOR, had a 3-fold increase in lung tissue after LPS stimulation, but the increase was blocked by Rapa. Rapa reduced the levels of TNF-alpha (LPS vs. LPS + Rapa, (1672.74 +/- 193.73) vs. (539.17 +/- 140.48) pg/ml, respectively; P < 0.01) and IL-6 (LPS vs. LPS + Rapa: (7790.88 +/- 1170.54) vs. (1968.57 +/- 474.62) pg/ml, respectively; P < 0.01) in the BAL fluid. However, Rapa had limited effects on the overall severity of ALI, as determined by the wet-to-dry weight ratio of the lungs, number of neutrophils in the BAL fluid, and changes in histopathology. In addition, Rapa failed to reduce mortality in the LPS-induced ALI model. CONCLUSIONS: We confirmed that mTOR was activated during LPS-induced ALI and strongly inhibited by Rapa. Although Rapa reduced the levels of the mediators of inflammation, the overall severity and survival of the ALI murine model were unchanged. PMID- 22040566 TI - Comparative study on the stem cell phenotypes of C6 cells under different culture conditions. AB - BACKGROUND: Glioma stem cell (GSC) hypothesis posits that a subpopulation of cells within gliomas have true clonogenic and tumorigenic potential. Significantly, a more controversial correlate to GSC is that cells in different culture conditions might display distinct stem cell properties. Considering these possibilities, we applied an approach comparing stem cell characteristics of C6 glioma cells under different culture conditions. METHODS: C6 cells were cultured under three different growth conditions, i.e., adherent growth in conventional 10% serum medium, non-adherent spheres growth in serum-free medium, as well as adherent growth on laminin-coated flask in serum-free medium. Growth characteristics were detected contrastively through neurosphere formation assay and cell cycle analysis. Markers were determined by immunofluorescence, relative quantitative reverse transcription (RT)-PCR, Western blotting and flow cytometry. Side population cells were analyzed via flow cytometry. Tumor models were detected by magnetic resonance imaging and hematoxylin & eosin staining. Data analyses were performed with SPSS software (17.0). RESULTS: C6 cells (C6-Adh, C6 SC-Sph and C6-SC-Adh) showed distinctive growth patterns and proliferation capacity. Compared to suspending C6-SC-Sph, adherent C6-Adh and C6-SC-Adh displayed higher growth ratio. C6-SC-Sph and C6-SC-Adh showed enhanced capability of neurosphere formation and self-renewal. High side population ratio was detected in C6-SC-Sph and C6-SC-Adh. CD133 was not detected in all three kinds of cells. Conversely, Nestin and beta-III-tubulin were demonstrated positive, nonetheless with no statistical significance (P > 0.05). Interestingly, lower expression of glial fibrillary acidic protein was demonstrated in C6-SC-Sph and C6-SC-Adh. C6-Adh, C6-SC-Sph and C6-SC-Adh were all displayed in situ oncogenicity, while statistical difference of survival time was not confirmed. CONCLUSIONS: C6 glioma cell line is endowed with some GSC phenotypes that can be moderately enriched in vitro when transferred into stem cell culture condition. The resultant tumor-spheres may be not a prerequisite or sound source of GSCs and adherent culture in stem cell medium is not a growth condition in favor of GSCs expanding in vivo. PMID- 22040567 TI - Corticosterone rapidly promotes respiratory burst of mouse peritoneal macrophages via non-genomic mechanism. AB - BACKGROUND: The immunomodulatory effects of glucocorticoids (GCs) have been described as bimodal. High concentration of GCs exerts immunosuppressive effects and low levels of GCs are immunopermissive. While the immunosuppressive mechanisms of GCs have been investigated intensely, the immunopermissive effects of GCs remain unclear. A lot of studies showed GCs could exert rapid non-genomic actions. We herein studied the rapid immunopromoting effects of GCs. METHODS: We observed the rapid (within 30 minutes) effects of corticosterone on respiratory burst of mouse peritoneal macrophages and studied their mechanisms. The superoxide anions were measured by cytochrome C reduction assay. Protein kinase C phosphorylation was measured by Western blotting and membrane fluidity was evaluated by fluorescence polarization measurement. RESULTS: The 10(-8) mol/L and 10(-7) mol/L corticosterone rapidly increased the superoxide anions production by macrophages, which were insensitive to GC-receptor antagonist, mifepristone, and protein-synthesis inhibitor, cycloheximide. Corticosterone coupled to bovine serum albumin was able to mimic the effects of corticosterone. The effects were independent of protein kinase C pathway and the change in membrane fluidity. CONCLUSIONS: The results indicate that corticosterone rapidly promote the superoxide anions production by mouse peritoneal macrophages may through non genomic mechanisms. This study may contribute to understanding the effects of GCs under stress condition and the physiological significance of nongenomic effects of GCs. PMID- 22040568 TI - Effect of human epididymis protein 4 gene silencing on the malignant phenotype in ovarian cancer. AB - BACKGROUND: Human epididymis secretory protein 4 (HE4) has been proved to be a promising novel biomarker for the detection of epithelial ovarian carcinomas. Compared with CA125, HE4 assay demonstrated an improved ability to discriminate between pelvic mass with malignant and benign disease. Though it is well known that HE4 is overexpressed in ovarian cancer, however, the role of HE4 in the carcinogenesis and progression of ovarian cancer remains unkown. METHODS: In this study, we explored the role of HE4 in the carcinogenesis and progression of ovarian cancer. We screened nine ovarian cancer cell lines for HE4 expression, and using RNA interference (RNAi), we silenced HE4 gene expression in CaoV3 and SKOV3.ip1 ovarian cancer cell lines. We assessed the effect of HE4 gene silencing on the transformed phenotype by examining the cell cycle, apoptosis, proliferation and transwell migration/invasion in vitro. RESULTS: HE4 gene silencing induces G0/G1 arrest and blocks the progression from the G1 to S phase in CaoV3 and SKOV3.ip1 cells. HE4 knockdown also inhibited cell proliferation, migration and invasion in SKOV3.ip1 cells in vitro. CONCLUSION: HE4 may be involved in the regulation of the cell cycle and promote ovarian cancer migration and invasion. PMID- 22040569 TI - Inhibition of nitric oxide synthase lowers fatty acid oxidation in preeclampsia like mice at early gestational stage. AB - BACKGROUND: Preeclampsia is one of hypertensive disorders in pregnancy. It is associated with abnormal lipid metabolism, including fatty acid oxidation metabolism. Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) plays an indispensable role in the oxidation of fatty acids. It has been reported that nitric oxide (NO) is one of the regulatory factors of the fatty acid oxidation pathway. The aim of this research was to investigate whether the nitric oxide synthase (NOS) inhibitor L-NAME may cause down-regulation of LCHAD in the pathogenesis of preeclampsia. METHODS: Pregnant wild-type (WT) mice were treated with L-NAME or normal saline (NS) during gestation days 7 - 18 (early group), days 11 - 18 (mid group) and days 16 - 18 (late group), and apoE-/- mice served as a control. Systolic blood pressure (SBP), urine protein, feto-placental outcome, plasma lipid levels and NO concentrations were measured, and the expression of mRNA and protein for LCHAD in placental tissue were determined by real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively. RESULTS: In WT and apoE-/- mice, SBP and urinary protein increased following L NAME injection. Fetal and placental weights and NO concentrations were reduced and total cholesterol, triglycerides and free fatty acid levels were increased in early and mid L-NAME groups in WT and apoE-/- mice, compared with the NS group. There was no significant difference between the late L-NAME group and NS group. RT-PCR and Western blotting analysis showed that the mRNA and protein levels of LCHAD expression were significantly down-regulated in the early and mid L-NAME groups but not in the late L-NAME group in the WT and apoE-/- mice compared with the corresponding NS groups. CONCLUSIONS: Inhibition of NO in early and mid gestation in mice may cause hyperlipidemia and suppression of fatty acid oxidation, whereas preeclampsia-like conditions in late gestation may be a maternal vascular response to inhibition of NO. PMID- 22040570 TI - Reperfusion of the rat brain tissues following acute ischemia: the correlation among diffusion-weighted imaging, histopathology, and aquaporin-4 expression. AB - BACKGROUND: Although some studies have reported that aquaporin-4 (AQP4) plays a role in the post-ischemic edema formation and diffusion-weighted imaging (DWI), little is known about the AQP4 expression in stage of the reperfusion following acute cerebral ischemia, as well as the correlation between histopathology and DWI. The aim of the study was to investigate the correlation among DWI, histopathology and the AQP4 expression in the reperfused rat brain tissues following acute ischemia. METHODS: Seventy Wistar rats were randomly divided into a control group (group A), and several occluded and reperfusion groups. They had their middle cerebral artery unilaterally occluded (MCAO) for 30 minutes (group B) followed by 30 minutes (group D) or 60 minutes (group E) of reperfusion, or 60 minutes of MCAO (group C) followed by 30 minutes (group F), or 60 minutes (group G) of reperfusion (n = 10 for each group). All rats underwent DWI scanning. The relative apparent diffusion coefficient (rADC) value of each rat was calculated. All the rats were sacrificed and the cerebral ischemic tissues were examined for histopathology. Real-time fluro-quantitative polymerase chain reaction (RT-PCR) and Western-blotting were performed. The amount of AQP4 mRNA (Ex(-DeltaDeltaCt)) and AQP4 protein (Q) was statistically analyzed. The correlation between rADC values and AQP4 mRNA expression was analyzed with the Pearson correlation test. RESULTS: In all the reperfusion groups, the areas of hyper-intensity signal in DWI were decreased, and the rADC value increased and the AQP4 expression decreased significantly compared with the occluded group (t = 26.89, t = 18.26, P < 0.01). There was a negative correlation between AQP4 mRNA expression and rADC values (r = -0.72, P < 0.01). A mixed edema, composed of cerebral intracelluar edema and vasogenic brain edema, was observed in all the reperfusion groups. It was more prevalent in groups D and F than in the groups E and G. With the reperfusion time postponed, the cerebral intracelluar edema of the rat was significantly mitigated, but the vasogenic brain edema was not significantly changed. CONCLUSIONS: There is a close correlation between AQP4 expression and the cerebral intracellular edema. The change of ADC values may indirectly reflect the level of the AQP4 expression. DWI may become a promising, noninvasive imaging modality to predict early stroke and reperfusion injury. PMID- 22040571 TI - T-cell proliferation is inhibited by the induction of indoleamine 2,3-dioxygenase in spleen-derived dendritic cells in rat. AB - BACKGROUND: Increasing evidence suggests that, by the production of indoleamine 2,3-dioxygenase (IDO), dendritic cells (DC) may reduce the activity of T lymphocytes and inhibit T lymphocyte proliferation-induced immune tolerance. One promising way is inspired by increasing IDO expression in DC cells for immune tolerance after transplantation. The aim of this work was to examine the effect of interferon-gamma (IFN-gamma) on the expression of IDO by DC. METHODS: Spleen derived rat DCs were cultured and induced by cytokines, and the expression of OX62 and surface molecules CD80 and CD86 were measured with flow cytometry. After the DCs were induced by IFN-gamma at different concentrations (0, 100, 300, 500 U/ml), the expression levels of IDO mRNA were measured with real-time PCR, and the expression levels of IDO protein in DCs were measured with Western blotting. The allogeneic mixed lymphocyte reaction (MLR) was used to test the effects of DCs incubated with different concentrations of IFN-gamma on allogeneic T lymphocyte proliferation. RESULTS: Under the microscope, the DCs induced by IFN gamma showed a typical dendritic morphology. The expression rate of OX62 was above 80% and the positive expression rates of CD80 and CD86 were both about 80%. The expressions of IDO mRNA and IDO protein increased gradually with the increase of IFN-gamma concentration, showing statistical significance in the differences between the groups (P < 0.05). Compared with the control DC, the DC incubated with IFN-gamma had a notable decrease in allostimulatory activity (P < 0.05). With the increasing IFN-gamma concentration, the T lymphocyte proliferation decreased, and the difference between the groups was also statistically significant (P < 0.05). CONCLUSIONS: The highly purified spleen derived rat DCs can be successfully acquired through the improved adhesion in-vitro method. IFN gamma can induce increased expression of IDO in spleen-derived rat DCs and reduce the spleen DCs' capacity to stimulate the proliferation of allogeneic T cells. PMID- 22040572 TI - Recombinant adenovirus with human indoleamine-2,3-dioxygenase and hepatitis B virus preS was constructed and expressed in HepG2 cells. AB - BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) is proven to suppress hepatitis B virus (HBV) specific immune response and depletion of IDO may be a useful approach for HBV therapy. To test this concept, we constructed recombinant adenovirus with human IDO and HBV preS, which would form the basis for future in vivo experiments. METHODS: The fragment of human IDO and HBV preS cDNA were subcloned into multiple cloning sites in an adenoviral vector system containing two cytomegalovirus (CMV) promoters. Recombination was conducted in the Escherichia coli BJ5183. The recombinant adenovirus containing hIDO gene and HBVpreS gene was packaged and amplified in 293 cells. Integration was confirmed by polymerase chain reaction as well as the quantification of viral titers. HepG2 cells were infected with the recombinant adenovirus and mRNA and protein specific for hIDO and HBVpreS was detected by RT-PCR and Western blotting respectively. RESULTS: The recombinant adenovirus was produced successfully. Its titer was 2.5 * 10(9) efu/ml. IDO and HBVpreS mRNA as well as the encoded proteins could be found in transfected HepG2 cells, but not in control HepG2 cells. CONCLUSION: The transfer of hIDO-HBVpreS with double-promoter adenoviral vector was efficient. The recombinant adenovirus with hIDO and HBV preS would provide the experimental basis for future studies. PMID- 22040573 TI - miRNA deregulation in multiple myeloma. AB - Multiple myeloma (MM) is an incurable plasma cell malignancy and is the second most common hematological cancer. It is characterized by complex, recurrent genetic and epigenetic abnormalities. Recent publications have linked miRNAs, a novel class of gene regulators to cancer including MM. miRNAs are about 20 nucleotide, single strand, non-coding RNAs that repress gene expression by mRNA degradation or translational repression. Aberrant miRNA expression profiles have been described in MM, and their functional roles in MM pathogenesis are being increasingly recognized. This review summarizes the current literature on the role of miRNAs in MM and offers perspectives on future research and utilization of miRNAs in MM management. PMID- 22040574 TI - Translational research and its effects on medicine in China. AB - Translational research has become a globally recognized model of medical research. Chinese government and doctors have begun to discuss the plan for its development. But most articles are focusing on the advantages rather than its pros and cons. In this essay, the authors discuss the disadvantages of translational research, its effects on clinical work and medical education, highlighting some potential problems and risks in theory and practice on case basis. Some important research management requirements are summarized in this essay to help bring the therapy from the research laboratory to the patient's bedside. PMID- 22040575 TI - Community survey, treatment and long-term follow-up for human cystic echinococcosis in northwest China. AB - BACKGROUND: Human cystic echinococcosis (CE) is a parasitic zoonosis of major public health importance throughout the world. CE is endemic throughout central Asia including northwestern China. In China, CE has been reported in 21 provinces, autonomous regions and municipalities, covering approximately 87% of China's territories. It is most common in the pastoral and semi-pastoral western provinces and regions. This study aimed to reveal the natural history, curative effect and possible re-infection risk factors of human CE through long termed follow-up of treated and untreated CE cases in Hobukesar, Xingjiang, China. METHODS: Follow-up studies on CE were performed twice in Hobukesar from August 2005 to October 2008, after an initial mass screening performed in 1995 and 1996. Ultrasound scan was the primary diagnostic method. RESULTS: Among 24 patients with confirmed CE, 22 were treated (surgery in 19 and chemotherapy in three). Two recurrent cases and one re-infection case were subsequently found during follow up. The CE type of one of the recurrent cases reverted from CE4 to CE3, as classified using World Health Organization (WHO) guidelines. CONCLUSIONS: Ultrasound was required to differentiate primary, recurrent and re-infection cases during epidemiological investigation and follow-up of CE. Most patients did not change their habits, which may be one possible cause of reinfection. One recurrent case suggested that, despite initial suggestion from the WHO Informal Working Group on Echinococcosis, CE4-type cysts are not inactive. PMID- 22040576 TI - Thin steel plate with thumbtack fixation in the treatment of massive presacral venous plexus hemorrhage. AB - BACKGROUND: Massive presacral venous plexus hemorrhage during radical resection of rectal carcinoma is rare, but when it occurs, bleeding can be uncontrollable, leading to death in some cases. Medical adhesive gauze sticking and packing and thumbtack compressive fixation are often used for hemostasis, but these methods are not effective in cases of uncontrollable massive hemorrhage. Therefore, identifying a practical, accurate, and reliable method of hemostasis in these cases is essential. METHODS: Between January 2004 and December 2009, we treated 3 patients with massive presacral venous plexus hemorrhage during resection of rectal carcinoma by placing small, trimmed thin steel plates at the bleeding sites. The plates were fixed with a saddle-type application of thumbtacks. RESULTS: Bleeding was successfully controlled in all 3 patients, and intestinal anastomosis was carried out after hemostasis. No complications were observed. CONCLUSIONS: Application of a small, thin steel plate to the bleeding site with thumbtack fixation is a simple and effective method of hemostasis in patients with massive presacral venous plexus hemorrhage during resection of rectal carcinoma. PMID- 22040577 TI - Fibrovascular polyp of the hypopharynx and esophagus. AB - Fibrovascular polyp of the hypopharynx and esophagus, a rare, benign, intraluminal and submucosal tumor, is most commonly originated from the proximal esophagus. We discussed four cases with regurgitation, respiratory symptom or the feeling of a mass in the throat. All the patients were examined with laryngoscope under general anesthesia. A transverse cervical incision was performed in one patient and the polyps were excised under laryngoscope with CO2 laser in the other three patients. All the lesions were removed successfully. Diagnostic and therapeutic principles involved in these cases are presented and discussed. The recognition of fibrovascular polyp of the hypopharynx and esophagus as a potential cause of regurgitation is paramount. Surgical excision is recommended because of the satisfactory outcome. PMID- 22040578 TI - Biological artificial vessel graft in distal arterial bypass for treating diabetic lower limb ischemia: a case report. AB - A 68-year-old female patient was treated for unhealed ulcer in the fourth toe of the left foot. Clinical examinations identified severe stenosis of the proximal segment and occlusion of the distal segment of the left anterior tibial artery, and occlusion of the left posterior tibial artery and the peroneal artery. The proximal stenotic segment of the left anterior tibial artery was dilated, but the distal occlusive part failed to be re-canalized. Left anterior tibial artery to dorsal pedal artery bypass was performed on the patient with an epoxide crosslinked, special radicals antigen-sealed, porcine-derived biological graft; debridement of the left 4th digiti pedis was also performed. Postoperation course was uneventful. The pulse of the left dorsal pedal artery was strong. The ankle brachial index (ABI) increased from 0.60 to 1.09. Warfarin and two antiplatelet drugs were given after the operation. Six months after operation, computed tomographic angiogram (CTA) identified the patent graft. PMID- 22040579 TI - Recombinant activated factor VII in hemophagocytic lymphohistiocytosis with disseminated intravascular coagulation. AB - Hemophagocytic lymphohistiocytosis (HLH) is a lifethreatening disorder due to hyperinflammation resulting in infiltration of different organs with extensive hemophagocytosis. Severe coagulopathy was one of the main reasons for death in HLH. Over secretion of plasminogen activator by activated macrophages leads to hyperfibrinolysis. We reported a 36-year-old woman who was diagnosed as HLH probably secondary to lymphoma. Massive bleeding from gut and retroperitoneal area were not able to be controlled by conventional hemostatic treatments. This patient received one dose recombinant activated factor VII (rFVIIa) 3.6 mg (70 MUg/kg). Hemostatic effect was achieved in 0.5 hour and lasted 24 hours. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were quickly corrected to normal ranges. Fibrinogen level elevated from 0.5 g/L before using rFVIIa to 1.8 g/L 20 hours after. Although dexamethasone and etopside were administrated to treat HLH, this patient died from septic shock after persistent neutropenia. This suggests that rFVIIa may be effective in the management of intractable hemorrhage in patients with HLH. PMID- 22040580 TI - Atypical Cogan's syndrome associated with coronary disease. AB - Cogan's syndrome (CS) is a rare inflammatory disorder characterized by interstitial keratitis and vestibuloauditory abnormalities often associated with various systemic manifestations. Involvement of cardiovascular system resembling systemic vasculitis may lead to severe complications and death. The present report describes a case of a female patient with atypical Cogan's syndrome presented with systemic manifestations and severe coronary and femoral artery stenosis. Despite the clinical improvement after glucocorticoids and cyclophosphamide, the patient required double aortocoronal bypass grafting one year letter. During three years follow-up, she was in stable condition, without stenocardial symptoms and claudication and her inflammatory parameters remain normal. This case highlights the rare involvement of coronary arteries without associated large-vessel vasculitis of the aortic arch in CS. PMID- 22040581 TI - Magnetic resonance imaging of unilateral vertical retraction syndrome with atypical strabismus. AB - We report two patients with unilateral vertical retraction syndrome. Magnetic resonance imaging (MRI) of the orbits of the two cases showed similar size and location of the orbital structure, but with dramatically different strabismus type. MRI sagittal reconstruction of the orbits suggested that abnormal muscle tissue arised from the inferior rectus, which might be associated with retraction and narrowing of the palpebral fissure and atypical strabismus as well. PMID- 22040582 TI - Late recurrent high degree atrioventricular block after percutaneous closure of a perimembranous ventricular septal defect. AB - High degree atrioventricular block (HDAVB) is a serious complication of transcatheter closure of a perimembranous ventricular septal defect (PMVSD). We report one patient who developed transient HDAVB seven days after transcathter closure of PMVSD and had recurrent HDAVB 42 months after the procedure. PMID- 22040584 TI - Infrared imaging and spectral-domain optical coherence tomography findings correlate with microperimetry in acute macular neuroretinopathy: a case report. AB - INTRODUCTION: Spectral-domain optical coherence tomography findings in a patient with acute macular neuroretinopathy, and correlation with functional defects on microperimetry, are presented. CASE PRESENTATION: A 25-year old Caucasian woman presented with bitemporal field defects following an upper respiratory tract infection. Her visual acuity was 20/20 in both eyes and a dilated fundus examination revealed bilateral hyperpigmentary changes in the papillomacular bundle. Our patient underwent further evaluation with spectral-domain optical coherence tomography, infrared and fundus autofluorescence imaging. Functional changes were assessed by microperimetry. Infrared imaging showed the classic wedge-shaped defects and spectral-domain optical coherence tomography exhibited changes at the inner segment-outer segment junction, with a thickened outer plexiform layer overlying these areas. Fluorescein and indocyanine green angiography did not demonstrate any perfusion defects or any other abnormality. Microperimetry demonstrated focal elevation in threshold correlating with the wedge-shaped defects in both eyes. CONCLUSION: Spectral-domain optical coherence tomography findings provide new evidence of the involvement of the outer plexiform layer of the retina in acute macular neuroretinopathy. PMID- 22040585 TI - Post-traumatic stress disorder and health risk behaviors among Afghanistan and Iraq War veterans attending college. AB - OBJECTIVE: To determine if post-traumatic stress disorder (PTSD) is associated with health risk behaviors among Operations Enduring and Iraqi Freedom (OEF/OIF) veterans attending college. METHOD: Using 2008 Boynton College Student Health Survey data, we tested associations between self-reported PTSD diagnosis and self reported risk behaviors (n=406). RESULTS: We found PTSD diagnosis to be significantly associated with reporting involvement in a physical fight in the past year (ARR = 3.1; 95% CI: 2.2, 4.4) and marginally associated with highrisk drinking (ARR = 1.3; 95% CI: 1.1, 1.6). However, no association was seen between PTSD and the tobacco use and other safety behaviors that we examined. CONCLUSION: PTSD is likely a factor that contributes to the relationship between military service and certain health risk behaviors. PMID- 22040586 TI - Knowledge and attitudes about colon cancer screening among African Americans. AB - OBJECTIVES: To explore knowledge and attitudes about colorectal cancer (CRC) screening among African American patients age 45 and older at a community health center serving low-income and uninsured patients. METHODS: We conducted 7 focus groups and 17 additional semistructured interviews. Sessions were audio recorded, transcribed, and analyzed using standard text analysis. RESULTS: Most participants who were age eligible for CRC screening were nonadherent according to national guidelines. Themes included low CRC knowledge, low perceived norms, high barriers, and other screening beliefs. CONCLUSION: Lack of knowledge, low perceived risk, and attitudes about CRC screening may be important targets for interventions in low-income African American patients. PMID- 22040587 TI - The role of hope in engaging in healthy behaviors among college students. AB - OBJECTIVES: To examine hope in relation to alcohol use, binge drinking, smoking, exercise, and limiting of dietary fat among college students. METHODS: Undergraduate students (N=2265) completed an online survey. RESULTS: Lower hope scores were related to binge drinking and smoking in the past month and more frequent drinking and binge drinking, controlling for sociodemographics. Higher hope scores were related to greater likelihood of and more frequent exercising and fat limitation in the past month. CONCLUSIONS: Interventions to improve college student health behaviors should target hope. PMID- 22040588 TI - APC modeling of smoking prevalence among US adolescents and young adults. AB - OBJECTIVE: To investigate the association of age, period, and cohort with the changing pattern of cigarette smoking among youth and young adults for better planning tobacco control in the United States. METHODS: Age-period-cohort analysis of the 1990-2005 National Survey on Drug Use and Health data. RESULTS: Rates of lifetime and 30-day smoking for adolescents fluctuated between 1990 and 1996 before they declined; the same rates for young adults progressively increased until 2002 before declining. There were significant cohort effects on changes in the prevalence rates of cigarette smoking. CONCLUSIONS: The cohort effects on smoking underscore the need for sustained tobacco control policies. PMID- 22040589 TI - Social cognitive mediators of parent-child sexual communication. AB - OBJECTIVE: To test a social cognitive behavior change model and identify mediators of the effects of the Parents Speak Up National Campaign (PSUNC) on parent-child sexual communication. METHODS: Investigators used 5 waves of data from an online randomized controlled trial. Latent variables were developed based on item response theory and confirmatory factor analysis. Structural equation modeling was used to test mediation. RESULTS: Outcome expectations mediated effects of social norms and self-efficacy on sexual communication. Other hypothesized mediators were not confirmed. CONCLUSIONS: Interventions to promote parent-child sexual communication should target outcome expectations. Future research should investigate parents' health information seeking. PMID- 22040590 TI - Consumption of sport-related dietary supplements among NCAA Division 1 female student athletes. AB - OBJECTIVES: To determine factors that influence sport-related dietary supplement consumption among NCAA Division 1 female student athletes and to estimate the plausibility of the theory of planned behavior (TPB) for predicting the use of sport-related dietary supplements among NCAA Division 1 female student athletes. METHOD: Self-report data were collected by questionnaire from 207 NCAA Division 1 female student athletes. Parameter estimates of 3 TPB-based models were calculated using Mplus software. RESULTS: The TPB-based models explained 64-66% and 18% of variance in behavioral intention and behavior, respectively, with subjective norm being the strongest predictor of dietary supplement consumption intention. CONCLUSIONS: Results support plausibility for the TPB to predict sport related dietary supplement consumption among NCAA Division 1 female student athletes. PMID- 22040591 TI - Using zero-inflated models to explain chronic illness, pain, and complementary and alternative medicine use. AB - OBJECTIVE: To extend knowledge of complementary and alternative medicine (CAM) use by understanding how poor health influences both trying CAM and number of CAM types used. METHODS: Using the 2002 National Health Interview Survey's Supplemental Section, zero-inflated models were employed to examine CAM use across 5 domains. RESULTS: Results indicate that level of pain is the only consistent predictor of both the likelihood of trying CAM and how many types of CAM are used. Pain increased the odds ratio and number of CAM types used across all domains. Findings, however, were mixed for health status and chronic conditions. Only prayer was associated with higher odds ratio (OR=1.705, P<.001) and number of CAM types used for chronic illnesses (OR=1.024, P<.01). CONCLUSIONS: Expanding to zero-inflated models demonstrates variation in CAM use behaviors. Pain is the only consistent predictor of both trying CAM and the number of CAM types used. Chronic illness is only consistently influential for prayer. PMID- 22040592 TI - A qualitative investigation of obese men's experiences with their weight. AB - OBJECTIVES: To investigate obese men's health behaviors and strategies for change. METHODS: Qualitative interviews with 36 men (BMI 30 and over). RESULTS: All men felt personally responsible for their weight gain. Sedentary lifestyles, stress, lack of worklife balance and weight-based stigma were all significant causes of weight gain and barriers to weight loss. These factors also contributed to men's unwillingness to seek help for their over-weight. CONCLUSION: Addressing the self-blame and stigma associated with obesity is important in developing strategies to improve the health and well-being of obese men. PMID- 22040593 TI - Modifiable prostate cancer risk reduction and early detection behaviors in black men. AB - OBJECTIVE: To explore the personal factors related to modifiable prostate cancer risk-reduction and detection behaviors among black men. METHODS: Three thousand four hundred thirty (3430) black men were surveyed and structural equation modeling employed to test study hypotheses. RESULTS: Modifiable prostate cancer risk-reduction behavior was found to be influenced by perceived severity, cues to action, knowledge, and behavioral control. Prostate cancer detection behavior was determined by perceived susceptibility, attitude, perceived behavioral control, knowledge, and acculturation. CONCLUSION: The confirmed associations underscore the importance of cognitive-behavioral factors in the promotion of CaP risk reduction behavior as well as early detection among black men. PMID- 22040594 TI - Who's behind the wheel? Driving with medically intractable epilepsy. AB - OBJECTIVES: To examine driving in the context of people with medically intractable epilepsy, a population generally discouraged from driving. METHODS: This study tested the relationship between a comprehensive set of factors and driving among 190 patients with a currently valid driver's license who were being evaluated for epilepsy surgery. RESULTS: Almost one third (32.6%) of the sample reported currently driving. Distributional comparisons by current driving status revealed driving was significantly more prevalent among patients who were employed full-time and those who had not experienced a seizure-related MVA. CONCLUSIONS: The decision not to drive in the context of a chronic medical condition is complex and influenced by a myriad of factors such as perceived illness susceptibility and severity. PMID- 22040595 TI - Correlates of overweight status in Chinese youth: an East-West paradox. AB - OBJECTIVE: To examine the odds of overweight and related correlates in Chinese adolescents. METHOD: Cross-sectional study in 9023 adolescents. RESULTS: Chinese youth were more likely to be overweight if they spent more time being sedentary; slept <7 hours/night; were male; were younger; participated more in vigorous physical activity; and had higher levels of parental education, a higher frequency of vegetable intake, and a lower frequency of sweet/fast food intake. CONCLUSIONS: Overweight-related correlates seem to play different roles in the Chinese culture than in Western cultures. This may be due to culture-specific perceptions and changes in lifestyle accompanying socioeconomic transitions. PMID- 22040596 TI - Independent modulation of motion and vection aftereffects revealed by using coherent oscillation and random jitter in optic flow. AB - We added simulated vertical viewpoint jitter and oscillation to radial optic flow displays designed to induce forward vection. Display jitter and oscillation were both found to increase vection strength during, and reduce motion aftereffects (MAE) following, exposure to the optic flow (compared to no-jitter controls). Display jitter, which induced the strongest vection of all the conditions tested, was also found to increase the duration of vection aftereffects (VAE). PMID- 22040597 TI - Outcomes of usual chiropractic, harm & efficacy, the ouch study: study protocol for a randomized controlled trial. AB - BACKGROUND: Previous studies have demonstrated that adverse events occur during chiropractic treatment. However, because of these studies design we do not know the frequency and extent of these events when compared to sham treatment. The principal aims of this study are to establish the frequency and severity of adverse effects from short term usual chiropractic treatment of the spine when compared to a sham treatment group. The secondary aim of this study is to establish the efficacy of usual short term chiropractic care for spinal pain when compared to a sham intervention. METHODS: One hundred and eighty participants will be randomly allocated to either usual chiropractic care or a sham intervention group. To be considered for inclusion the participants must have experienced non-specific spinal pain for at least one week. The study will be conducted at the clinics of registered chiropractors in Western Australia. Participants in each group will receive two treatments at intervals no less than one week. For the usual chiropractic care group, the selection of therapeutic techniques will be left to the chiropractors' discretion. For the sham intervention group, de-tuned ultrasound and de-tuned activator treatment will be applied by the chiropractors to the regions where spinal pain is experienced. Adverse events will be assessed two days after each appointment using a questionnaire developed for this study. The efficacy of short term chiropractic care for spinal pain will be examined at two week follow-up by assessing pain, physical function, minimum acceptable outcome, and satisfaction with care, with the use of the following outcome measures: Numerical Rating Scale, Functional Rating Index, Neck Disability Index, Minimum Acceptable Outcome Questionnaire, Oswestry Disability Index, and a global measure of treatment satisfaction. The statistician, outcome assessor, and participants will be blinded to treatment allocation. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000542998. PMID- 22040598 TI - Parents' dietary patterns are significantly correlated: findings from the Melbourne Infant Feeding Activity and Nutrition Trial Program. AB - The objectives of the present study were to identify dietary patterns independently in first-time mothers and fathers, and to examine whether these patterns were correlated within families. Dietary intakes were collected at baseline in the Melbourne Infant Feeding Activity and Nutrition Trial Program using a validated FFQ in 454 pairs of first-time mothers and fathers. Education level was reported in associated questionnaires. Principal components analyses included frequencies of fifty-five food groups and were performed independently in mothers and fathers. Spearman's correlation coefficients were used to assess associations between dietary pattern scores. A total of four dietary patterns were identified in mothers and fathers. Of these, three dietary patterns had similar characteristics between these two populations, namely 'Fruits and vegetables', 'High-energy snack and processed foods', 'High-fat foods' in mothers; and 'Fruits', 'High-energy snack and processed foods', 'High-fat foods' in fathers. The following two additional patterns were identified: 'Cereals and sweet foods' in mothers and 'Potatoes and vegetables' in fathers. Patterns incorporating healthier food items were found to be positively associated with parent education. An inverse association with education was found for the 'High fat foods' and 'High-energy snack and processed foods' dietary patterns. Qualitatively similar patterns between corresponding mothers and fathers were the most strongly correlated (rho = 0.34-0.45, P < 0.001). There were some differences in dietary patterns between mothers and fathers, suggesting that it is worth deriving patterns separately when considering couples, and more generally between men and women. Exploring how these various patterns correlate within households provides important insights to guide the development and implementation of family-based interventions. PMID- 22040599 TI - Adipocyte-secreted factors increase osteoblast proliferation and the OPG/RANKL ratio to influence osteoclast formation. AB - Several studies have reported a positive relationship of the body fat mass and bone density. However, it is not clear whether adipocyte-derived signaling molecules directly act on osteoblasts or osteoclasts. Therefore, we investigated the effect of fat cell-secreted factors on the proliferation and differentiation of preosteoblasts and the molecular mechanisms involved. This stimulation led to an increased proliferation of MC3T3-E1 and primary preosteoblastic cells (2.8 fold and 1.5-fold, respectively; p<0.0001), which could be reduced with inhibitors of protein tyrosine kinases, FGFR1 and PI3K. Concordantly, we found human adipocytes to secrete bFGF and bFGF to mimic the effect of adipocyte secreted factors. The ratio of OPG/RANKL secretion in primary human preosteoblasts increased 9-fold (mRNA and protein) when stimulated with adipocyte secreted factors. Moreover, osteoblasts which were prestimulated with adipocyte secreted factors inhibited the formation of osteoclasts. In conclusion, human adipocytes secrete factors that directly act on preosteoblasts and alter their crosstalk with osteoclasts. These in vitro findings reflect the higher bone mass in obese people and attribute it to effects of adipocyte-secreted factors on bone formation. PMID- 22040600 TI - The International Pediatric Adrenocortical Tumor Registry initiative: contributions to clinical, biological, and treatment advances in pediatric adrenocortical tumors. AB - Adrenocortical tumor (ACT), a rare tumor with a heterogeneous presentation, incompletely understood pathogenesis, and generally poor prognosis, occurs in 1-2 people per million and is even more uncommon in the pediatric population. Such rare cancers are a challenge to clinical practice. Exchange of experience, information, and data on rare cancers is lacking, and outcomes for these rare cancers could be improved through the establishment of an international registry. The establishment of the International Pediatric Adrenocortical Tumor Registry (IPACTR) in 1990 by the St. Jude Children's Research Hospital International Outreach Program offered a new opportunity to collect clinical and laboratory features, treatment practices, and outcome data for children with ACT, research this disease, and systematically investigate how to improve patient outcomes. These efforts will improve the availability of information for both patients and the medical community. PMID- 22040601 TI - Characterization of a novel five-transmembrane domain cholecystokinin-2 receptor splice variant identified in human tumors. AB - The cholecystokinin-2 receptor (CCK2R), is expressed in cancers where it contributes to tumor progression. The CCK2R is over-expressed in a sub-set of tumors, allowing its use in tumor targeting with a radiolabel ligand. Since discrepancies between mRNA levels and CCK2R binding sites were noticed, we searched for abnormally spliced variants in tumors from various origins having been previously reported to frequently express cholecystokinin receptors, such as medullary thyroid carcinomas, gastrointestinal stromal tumors, leiomyomas and leiomyosarcomas, and gastroenteropancreatic tumors. A variant of the CCK2R coding for a putative five-transmembrane domains receptor has been cloned. This variant represented as much as 6% of CCK2R levels. Ectopic expression in COS-7 cells revealed that this variant lacks biological activity due to its sequestration in endoplasmic reticulum. When co-expressed with the CCK2R, this variant diminished membrane density of the CCK2R and CCK2R-mediated activity (phospholipase-C and ERK activation). In conclusion, a novel splice variant acting as a dominant negative on membrane density of the CCK2R may be of importance for the pathophysiology of certain tumors and for their in vivo CCK2R-targeting. PMID- 22040602 TI - Recessive protective effect of ADIPOQ rs1501299 on cardiovascular diseases with type 2 diabetes: a meta-analysis. AB - The association between a common variant of the ADIPOQ gene rs1501299 (+276G>T) and cardiovascular diseases (CVDs) outcomes has been reported with many studies. However, the evidence is insufficient for strong conclusions regarding CVDs and ADIPOQ rs15011299 (+276G>T). We performed a meta-analysis about the association between ADIPOQ rs1501299 (+276G>T) and CVDs risk using a predefined protocol, including 15 published studies with 5868 cases and 10,744 controls. The pooled data suggested a recessive protective effect of ADIPOQ rs1501299 (+276G>T) on CVDs for type 2 diabetes (T2D) population: the TT homozygote individuals had a reduced risk of developing CVDs compared to the carriers of G allele (OR=0.74, 95% confidence interval (CI): 0.58, 0.94; p=0.013). But there is still not enough evidence to indicate the association of the ADIPOQ rs1501299 (+276G>T) and the development of cardiovascular diseases (CVDs) outcomes in general population. In conclusion, our meta-analysis suggested that the ADIPOQ rs1501299 (+276G>T) polymorphism is a low-risk factor for the development of CVDs with T2D, but the association of this polymorphism with the susceptibility to CVDs in other populations remains unknown. It could be presumed that the ADIPOQ rs1501299 (+276G>T) be a potential cause of susceptibility to CVDs in persons with T2D, and it gives a new opportunity to investigate the mechanisms of CVDs susceptibility in T2D patients. PMID- 22040604 TI - Proteomic profiling of hempseed proteins from Cheungsam. AB - Proteomic profiling of hempseed proteins from a non-drug type of industrial hemp (Cannabis sativa L.), Cheungsam, was conducted using two-dimensional gel electrophoresis and mass spectrometry. A total of 1102 protein spots were resolved on pH 3-10 immobilized pH gradient strips, and 168 unique protein spots were identified. The proteins were categorized based on function, including involvement in energy regulation (23%), metabolism (18%), stress response (16%), unclassified (12%), cytoskeleton (11%), binding function (5%), and protein synthesis (3%). These proteins might have important biological functions in hempseed, such as germination, storage, or development. PMID- 22040603 TI - Biosynthesis and antimicrobial evaluation of backbone-cyclized alpha-defensins. AB - Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. Upon stimulation by bacterial antigens, enteric alpha defensins are secreted into the intestinal lumen where they have potent microbicidal activities. Cryptdin-4 (Crp4) is an alpha-defensin expressed in Paneth cells of the mouse small intestine and the most bactericidal of the known cryptdin isoforms. The structure of Crp4 consists of a triple-stranded antiparallel beta-sheet but lacks three amino acids between the fourth and fifth cysteine residues, making them distinct from other alpha-defensins. The structure also reveals that the alpha-amino and C-terminal carboxylic groups are in the proximity of each other (d ~ 3 A) in the folded structure. We present here the biosynthesis of backbone-cyclized Crp4 using a modified protein splicing unit or intein. Our data show that cyclized Crp4 can be biosynthesized by using this approach both in vitro and in vivo, although the expression yield was significantly lower when the protein was produced inside the cell. The resulting cyclic defensins retained the native alpha-defensin fold and showed equivalent or better microbicidal activities against several Gram-positive and Gram-negative bacteria when compared to native Crp4. No detectable hemolytic activity against human red blood cells was observed for either native Crp4 or its cyclized variants. Moreover, both forms of Crp4 also showed high stability to degradation when incubated with human serum. Altogether, these results indicate the potential for backbone-cyclized defensins in the development of novel peptide-based antimicrobial compounds. PMID- 22040605 TI - Does theatre improve the quality of life of people with dementia? AB - BACKGROUND: A new communication method, the "Veder method", has recently been developed. Caregivers are trained to apply this method in a group activity ("living-room theatre activity") for people with dementia in which theatrical stimuli are used in combination with proven emotion-oriented care methods. The aim of this exploratory study was to evaluate the added value of the Veder method group activity compared to a regular reminiscence group activity and to investigate whether professional carers can achieve the same effects with the Veder method as professional actors. METHODS: A quasi-experimental three-group design was used. Experimental group 1 (E1; n = 65) joined a living-room theatre activity offered by trained professional caregivers. Experimental group 2 (E2; n = 31) joined a living-room theatre activity offered by professional actors. The control group (n = 55) received a usual reminiscence group activity. Behavior, mood and aspects of quality of life were measured using standardized observation scales at three points in time: (T1) pretest; (T2) during the intervention and; (T3) post-test, two hours after the intervention. RESULTS: During the intervention, significant differences were found in favor of the group that was offered a living-room theatre activity by actors (E2) on different aspects of behavior, mood and quality of life. At post-test, people in E2 were more alert compared to the control group. Moreover, they recalled more memories and showed less socially isolated behavior compared to the control group. CONCLUSION: This exploratory study shows that the Veder method has some clear positive effects on behavior and mood of people with dementia when applied by professional actors. PMID- 22040606 TI - Prokaryotic expression of woodchuck cytotoxic T lymphocyte antigen 4 (wCTLA-4) and preparation of polyclonal antibody to wCTLA-4. AB - Cytotoxic T lymphocyte antigen 4 (CTLA-4) is an inhibitory T cell receptor predominately expressed on activated T cells and plays an important role in regulation of specific T cell responses to viral infection. The woodchuck model is an informative animal model for hepatitis B virus (HBV) infection. In this study, the extracellular region of woodchuck CTLA-4 (wCTLA-4) was cloned and the fusion protein of GST-wCTLA-4 was expressed and purified. Polyclonal antibody against GST-wCTLA-4 (anti-GST-wCTLA-4) was prepared. The full length wCTLA-4 protein expressed in transfected baby hamster kidney cells was detected by anti GST-wCTLA-4 in western blot analysis and immunofluorescence staining. Anti-GST wCTLA-4 provides a useful tool to study the role of CTLA-4 in T-cell response in the woodchuck model. Further, the blocking of CTLA-4 with anti-GST-wCTLA-4, as a novel therapy approach for chronic hepatitis B virus infection, could be studied in woodchuck model now. PMID- 22040607 TI - Large-scale preparation and characterization of non-pegylated and pegylated superactive ovine leptin antagonist. AB - Superactive ovine leptin antagonist (SOLA) was prepared by rational mutagenesis of the ovine leptin antagonist L39A/D40A/F41A mutant prepared previously in our lab by mutating wild type leptin to D23L/L39A/D40A/F41A. SOLA was expressed in Escherichia coli as insoluble inclusion bodies, refolded and purified to homogeneity (as evidenced by SDS-PAGE and analytical gel filtration) by ion exchange chromatography. The purified protein was mono-pegylated at its N terminus by 20-kDa linear pegylation reagent. The D23L mutation resulted in ca. 5 to 6-fold increased affinity toward soluble human leptin binding domain and 6- to 8-fold increased inhibitory activity in two different in vitro bioassays. This increase was similar, though not identical, to our previous results with superactive mouse and human leptin antagonists. Pegylation decreased overall activity by 5- to 8-fold, but as shown previously for superactive mouse leptin antagonist, the prolonged half life in the circulation will likely result in higher activity in vivo. As amino acids 6-31 (VQDDTKTLIKTIVTRINDISHTQSVS), making up a main part of the first alpha-helix, are identical in human, mouse, rat, ovine, bovine and pig leptins, we anticipate that D23L mutations of the respective leptins will result in similar increases in affinity and consequent activity of other leptin antagonists. PMID- 22040608 TI - Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders. AB - BACKGROUND: Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene based, cell-based or pharmacological biotherapies. METHODS: Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders. RESULTS: The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both in vitro and in vivo after transplantation into regenerating muscle of immunodeficient mice. CONCLUSIONS: Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess in vivo the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies. PMID- 22040609 TI - Silage produces biofuel for local consumption. AB - BACKGROUND: In the normal process of bioethanol production, biomass is transported to integrated large factories for degradation to sugar, fermentation, and recovery of ethanol by distillation. Biomass nutrient loss occurs during preservation and degradation. Our aim was to develop a decentralized ethanol production system appropriate for farm or co-operative level production that uses a solid-state fermentation method for producing bio-ethanol from whole crops, provides cattle feed, and produces no wastes. The idea is to incorporate traditional silage methods with simultaneous saccharification and fermentation. Harvested, fresh biomass is ensiled with biomass-degrading enzymes and yeast. Multiple parallel reactions for biomass degradation and ethanol and lactic acid production are induced in solid culture in hermetically sealed containers at a ranch. After fermentation, ethanol is collected on site from the vapor from heated fermented products. RESULTS: The parallel reactions of simultaneous saccharification and fermentation were induced efficiently in the model fermentation system. In a laboratory-scale feasibility study of the process, 250 g of freshly harvested forage rice with 62% moisture was treated with 0.86 filter paper units/g dry matter (DM) of cellulase and 0.32 U/g DM of glucoamylase. After 20 days of incubation at 28 degrees C, 6.4 wt.% of ethanol in fresh matter (equivalent to 169 g/kg DM) was produced. When the 46 wt.% moisture was gathered as vapor from the fermented product, 74% of the produced ethanol was collected. Organic cellular contents (such as the amylase and pronase degradable fractions) were decreased by 63% and organic cell wall (fiber) content by 7% compared to silage prepared from the same material. CONCLUSIONS: We confirmed that efficient ethanol production is induced in nonsterilized whole rice plants in a laboratory scale solid-state fermentation system. For practical use of the method, further study is needed to scale-up the fermentation volume, develop an efficient ethanol recovery method, and evaluate the fermentation residue as an actual cattle feed. PMID- 22040610 TI - Generation of referring expressions: assessing the Incremental Algorithm. AB - A substantial amount of recent work in natural language generation has focused on the generation of ''one-shot'' referring expressions whose only aim is to identify a target referent. Dale and Reiter's Incremental Algorithm (IA) is often thought to be the best algorithm for maximizing the similarity to referring expressions produced by people. We test this hypothesis by eliciting referring expressions from human subjects and computing the similarity between the expressions elicited and the ones generated by algorithms. It turns out that the success of the IA depends substantially on the ''preference order'' (PO) employed by the IA, particularly in complex domains. While some POs cause the IA to produce referring expressions that are very similar to expressions produced by human subjects, others cause the IA to perform worse than its main competitors; moreover, it turns out to be difficult to predict the success of a PO on the basis of existing psycholinguistic findings or frequencies in corpora. We also examine the computational complexity of the algorithms in question and argue that there are no compelling reasons for preferring the IA over some of its main competitors on these grounds. We conclude that future research on the generation of referring expressions should explore alternatives to the IA, focusing on algorithms, inspired by the Greedy Algorithm, which do not work with a fixed PO. PMID- 22040611 TI - Piezoelectric-assisted removal of a benign fibrous histiocytoma of the mandible: an innovative technique for prevention of dentoalveolar nerve injury. AB - In this article, we present our experience with a piezoelectric-assisted surgical device by resection of a benign fibrous histiocytoma of the mandible.A 41 year old male was admitted to our hospital because of slowly progressive right buccal swelling. After further radiographic diagnosis surgical removal of the yellowish white mass was performed. Histologic analysis showed proliferating histiocytic cells with foamy, granular cytoplasm and no signs of malignancy. The tumor was positive for CD68 and vimentin in immunohistochemical staining. Therefore the tumor was diagnosed as primary benign fibrous histiocytoma. This work provides a new treatment device for benign mandibular tumour disease. By using a novel piezoelectric-assisted cutting device, protection of the dentoalveolar nerve could be achieved. PMID- 22040612 TI - Suction sampling as a significant source of error in molecular analysis of predator diets. AB - The molecular detection of predation is a fast growing field, allowing highly specific and sensitive detection of prey DNA within the gut contents or faeces of a predator. Like all molecular methods, this technique is prone to potential sources of error that can result in both false positive and false negative results. Here, we test the hypothesis that the use of suction samplers to collect predators from the field for later molecular analysis of predation will lead to high numbers of false positive results. We show that, contrary to previous published work, the use of suction samplers resulted in previously starved predators testing positive for aphid and collembolan DNA, either as a results of ectopic contamination or active predation in the collecting cup/bag. The contradictory evidence for false positive results, across different sampling protocols, sampling devices and different predator-prey systems, highlights the need for experimentation prior to mass field collections of predators to find techniques that minimise the risk of false positives. PMID- 22040613 TI - Parental youth assets and sexual activity: differences by race/ethnicity. AB - OBJECTIVES: To examine how the relationship between parental-related youth assets and youth sexual activity differed by race/ethnicity. METHODS: A random sample of 976 youth and their parents living in a Midwestern city participated in the study. Multivariate logistic regression analyses were conducted for 3 major ethnic groups controlling for the other demographics. RESULTS: Parental monitoring had the strongest association with sexual abstinence for all 3 ethnic/racial groups. Family communication and relationship with mother were also important for white and black youth respectively. CONCLUSIONS: Parental youth assets, especially parental monitoring, can be important in the decision to delay sexual intercourse. PMID- 22040614 TI - Men's knowledge and beliefs about colorectal cancer and 3 screenings: education, race, and screening status. AB - OBJECTIVE: To compare how education, race, and screening status affected men's knowledge about colorectal cancer and their views of 3 screenings: the fecal occult blood test (FOBT), sigmoidoscopy, and colonoscopy. METHODS: In-depth interviews were conducted with 65 African American and white men with diverse education backgrounds with similar numbers screened and unscreened. RESULTS: Education was associated with knowledge about colorectal cancer and the colonoscopy. Screening status and education were related to FOBT knowledge. Men knew little about the sigmoidoscopy. CONCLUSION: Intervention programs should tailor education about colorectal cancer and screening by educational attainment levels, not by race. PMID- 22040615 TI - Alcohol intoxication and occasional smoking: a field investigation. AB - OBJECTIVES: To test the relationship between alcohol intoxication and smoking behaviors in a field sample of 1139 young adults. METHODS: A self-administered survey and an objective measure of intoxication were used for data collection. We tested the relationship between smoking status and alcohol intoxication as well as the relationship between alcohol intoxication and smoking behaviors/intentions among occasional smokers. RESULTS: Occasional smokers were significantly more intoxicated than never smokers. Among occasional smokers, higher levels of intoxication were significantly associated with smoking behavior. CONCLUSIONS: The importance of using field studies to investigate the co-occurring use of alcohol and cigarettes is discussed. PMID- 22040617 TI - Potentials of qualitative modeling of complex health issues. AB - OBJECTIVE: To demonstrate the potentials of nutrition-ecological modeling (NutriMod) for integrative problem solving concerning complex health issues. METHODS: Causes and effects of the example overweight/obesity were depicted in their interrelatedness in a qualitative model within and across the dimensions health, environment, economy, and society. RESULTS: NutriMod facilitates problem analysis by visualizing the multitude of interrelated factors and promoting awareness to dynamics, multicausality, and multidimensionality. It allows considering key factors, underlying causes, and feedback loops. It supports discipline-transcending problem solving and predicting impacts of measurements. CONCLUSIONS: Modeling helps to understand complex health issues and to deal with their complexity and knowledge fragmentation. PMID- 22040616 TI - Emergency department-initiated tobacco dependence treatment. AB - OBJECTIVE: To examine the feasibility of a fax referral program to increase enrollment in tobacco dependence treatment in emergency department (ED) patients. METHODS: The control group received quit advice and printed information; the intervention group also received a faxed referral that generated telephone contacts. RESULTS: Treatment enrollment was higher in the intervention group (13.5% vs 2.7%). Only the faxed referral was associated with treatment enrollment. CONCLUSIONS: An ED intervention is feasible. Faxed referral resulted in a 5-fold increase in tobacco treatment enrollment. The ED may be an opportune setting to facilitate smoking-cessation behavior change among lower income, underserved patients. PMID- 22040618 TI - Changing intentions to use smokeless tobacco: an application of the IMB model. AB - OBJECTIVE: To determine if the Information-Motivation-Behavioral Skills model was effective for development of a smokeless tobacco educational unit (STEU) and analysis of STEU effects. METHODS: Structural equation modeling was used to test component relations proposed by the IMB model and STEU effects on parallel growth of IMB components. RESULTS: Results confirmed IMB model component relationships and indicated that STEU effects were primarily on information with indirect effects on expectancies and self-efficacy change through information. CONCLUSIONS: Prevention programming needs to address all IMB model components. Organizing analysis around the IMB model provides better understanding of program outcomes. PMID- 22040619 TI - The theory of planned behavior and helmet use among college students. AB - OBJECTIVES: To assess undergraduate helmet use attitudes and behaviors in accordance with the theory of planned behavior (TPB). We predicted helmet wearers and nonwearers would differ on our subscales. METHODS: Participants (N=414, 69% female, 84% white) completed a survey. RESULTS: Principal component analysis and reliability analysis guided the creation of subscales. Group differences were detected on 9 of 10 subscales: F(18,788) = 10.721, P=.001, eta(2) = .187. Few ethnicity and sex differences were detected. CONCLUSIONS: This study supports the validity of the TPB in predicting college student helmet use and offers a new scale for future research purposes. PMID- 22040620 TI - Variables associated with fruit and vegetable intake in adolescents. AB - OBJECTIVES: To assess individual, social, and family environmental factors related to fruit and vegetable intake among white and black adolescents aged 11 15 years (n=736). METHODS: Self-report questionnaire. RESULTS: Preferences, availability at home, family dinner frequency, snack choice, self-efficacy, modeling, normative beliefs, and social outcome expectations were significant associates of fruit and vegetable intake. Multivariate models indicated that these associations varied by categories of intake. Availability was the most consistent associate whereas fruit preference, availability, family dinner frequency, and self-efficacy were the strongest associates. CONCLUSIONS: Results highlight the important influence of the family environment on fruit and vegetable intake. PMID- 22040621 TI - Firefighter fitness, coronary heart disease, and sudden cardiac death risk. AB - OBJECTIVE: To determine the roles physical fitness, coronary heart disease, and sudden cardiac death risk play in firefighter culture, via an emic (insider's) perspective within the culture of the fire service. METHODS: Key informant interviews and focus group discussions with full-time, acculturated firefighters, framed within a social ecological framework. RESULTS: Physical fitness is a complex, cultural construct, based on functional capacity and management normative expectations. Coronary heart disease is not a culturally relevant reason for workplace fitness program adherence. CONCLUSIONS: Fitness interventions must culturally adapt to the unique nature of the fire service, emphasizing functional capacity, crew dependability, and fitness/well-being strategies. PMID- 22040622 TI - Home food and exercise environments of normal-weight and overweight adults. AB - OBJECTIVE: To examine the home environments of overweight and normal-weight adults and the relationships between the environment and weight-regulating behaviors. METHODS: Overweight (n=201) and normal-weight adults (n=213) assessed their homes via checklist and self-reported their eating and activity habits. RESULTS: OW adults had less exercise equipment, fewer low-fat snacks and fruits/vegetables, and more TVs, high-fat snacks, and spreads than did NW adults (Ps<.01). These variables were associated (Ps<.05) with weight-regulating behaviors. CONCLUSIONS: Increasing healthy foods and opportunities for physical activity within the home may improve weight-control efforts in adults. PMID- 22040623 TI - Relationship between smoking and obesity among women. AB - OBJECTIVES: To examine the relationship between smoking and weight status in adult women and whether this association differed by race. METHODS: The study sample consisted of 22,949 African American and 7831 white women enrolled in the Southern Community Cohort Study from 2002 to 2006. RESULTS: Both African American and white current smokers had decreased odds of being overweight or obese compared to normal-weight nonsmokers, and the inverse trends between current smoking and BMI held for both groups. CONCLUSION: A strong relationship exists between smoking and weight status, with patterns nearly identical for African Americans and white women. PMID- 22040624 TI - Development of microsatellite markers in Actinidia arguta (Actinidiaceae) based on the NCBI data platform. AB - PREMISE OF THE STUDY: Expressed sequence tag (EST)-derived microsatellite markers in Actinidia arguta were developed for genotyping and genetic mapping. METHODS AND RESULTS: One hundred and fifty EST-simple sequence repeat (SSR) primer pairs were obtained from the National Center for Biotechnology Information (NCBI) A. chinensis database using SSR Hunter 1.3. With the other 20 reported primers, 170 primer pairs were screened using 16 samples. A total of 72 primers pairs were successively developed for A. arguta. Fifteen of the developed markers were characterized in A. arguta populations from Changbai Mountain and Daba Mountain. The mean number of alleles per locus in the Changbai and Daba populations was 5.133 and 4.133, respectively. CONCLUSIONS: Development of Actinidia ESTs from the NCBI database is an effective method of obtaining SSR markers for A. arguta. These markers will be useful for genome mapping and molecular breeding in A. arguta. PMID- 22040625 TI - How young trees cope with removal of whole or parts of shoots: an analysis of local and distant responses to pruning in 1-year-old apple (Malus xdomestica; Rosaceae) trees. AB - PREMISE OF STUDY: Manipulation of tree architecture by pruning provides an experimental context to analyze architectural plasticity resulting from competition between developing organs. The objective of this study was to quantify the effects of the removal of all or part of shoots through pruning on the redistribution of growth and flowering at spatial and temporal levels. METHODS: Two types of pruning cuts were applied: (1) heading cuts of either the main stem or laterals and (2) thinning cuts (i.e., complete removal) of laterals. These two types of cuts were applied in summer and winter on 1-yr-old cultivars of Fuji and Braeburn apple trees. Tree topology and geometry were described over 3 years, and responses were analyzed for both local and distant scales. RESULTS: Heading cuts induced quasi-deterministic local responses on pruned axes, whereas responses to thinning cuts were more variable. For the main stem and laterals, responses over greater spatial and temporal scales were highlighted with (1) stronger growth the year after summer pruning and (2) modification of branching and flowering along the unpruned parts after winter pruning. CONCLUSIONS: Pruning typically induced growth redistribution toward traumatic reiterations and enhanced growth of the remaining unpruned axes with a concomitant decrease of flowering and cambial growth. Although results could be interpreted in relation to the root-shoot balance, tree responses appeared highly cultivar-specific. PMID- 22040626 TI - Psychometric evaluation of the Swedish version of the Person-Centered Care Assessment Tool (P-CAT). AB - BACKGROUND: Person-centered care is a multidimensional concept describing good care, especially within aged care and care for people with dementia. Research studies evaluating person-centered care interventions seldom use direct measurement of levels of person-centeredness. Existing scales that measure person centeredness need further testing. This study evaluated the psychometric properties of the Swedish version of the Person-Centered Care Assessment Tool (P CAT). METHODS: A cross-sectional sample of 1465 staff from 195 residential care units for older people in Sweden participated in the study. Validity, reliability, and discrimination ability of the scale were evaluated. RESULTS: Confirmatory factor analysis, parallel analysis and exploratory factor analysis supported the construct validity of a two-factor solution. Reliability and homogeneity were satisfactory for the whole P-CAT as demonstrated by a Cronbach's alpha of 0.75. Test-retest reliability showed temporal stability of the scale, and the discrimination ability of the scale was satisfactory. CONCLUSION: The Swedish version of the P-CAT was found to be valid, reliable, and applicable for further use. Two subscales are recommended for the Swedish version. PMID- 22040627 TI - Application of microtechnologies for the vascularization of engineered tissues. AB - Recent advances in medicine and healthcare allow people to live longer, increasing the need for the number of organ transplants. However, the number of organ donors has not been able to meet the demand, resulting in an organ shortage. The field of tissue engineering has emerged to produce organs to overcome this limitation. While tissue engineering of connective tissues such as skin and blood vessels have currently reached clinical studies, more complex organs are still far away from commercial availability due to pending challenges with in vitro engineering of 3D tissues. One of the major limitations of engineering large tissue structures is cell death resulting from the inability of nutrients to diffuse across large distances inside a scaffold. This task, carried out by the vasculature inside the body, has largely been described as one of the foremost important challenges in engineering 3D tissues since it remains one of the key steps for both in vitro production of tissue engineered construct and the in vivo integration of a transplanted tissue. This short review highlights the important challenges for vascularization and control of the microcirculatory system within engineered tissues, with particular emphasis on the use of microfabrication approaches. PMID- 22040628 TI - The cutting edge in esophageal physiology testing: equipment, uses, and analysis. AB - Advancements in foregut diagnostic technologies have led to improvements in the esophagologist's ability to accurately diagnose and classify esophageal pathophysiology and increased patient satisfaction and compliance in undergoing testing. The esophageal surgeon's ability to bring about a successful outcome is dependent on the proper application and interpretation of these diagnostic modalities. The ability to reliably and consistently differentiate foregut disorders from other potential contributors is an essential ingredient in assuring appropriate therapy and predicting success. The physician or surgeon treating esophageal disorders is well advised to keep abreast of ongoing advancements and to implement them into their diagnostic armamentarium. PMID- 22040629 TI - High-resolution manometry: an atlas of esophageal motility disorders and findings of GERD using esophageal pressure topography. AB - High-resolution manometry (HRM) has now become widely available and currently is moving into mainstream clinical practice. This article provides an HRM-related atlas of esophageal motility disorders focused on dysphagia and gastroesophageal reflux disease (GERD). Although there is some overlap between esophageal motor disorders associated with dysphagia and the defects and esophageal motor function that would predispose the patient to more severe GERD, this review is organized to differentiate the distinct pathophysiologic components of the two disease groups. A section on impaired bolus transit is also included to highlight the important aspect of impaired clearance in the pathogenesis of GERD. PMID- 22040630 TI - Evaluation and treatment of laryngopharyngeal reflux symptoms. AB - Gastroesophageal reflux disease (GERD) is a well-defined disease characterized by symptoms or complications caused by an abnormal amount of GER, which is a retrograde movement of gastric contents into the esophagus. Laryngopharyngeal reflux (LPR) is a subset of GERD and given its own identity, because the main symptomatic regions are the larynx and pharynx. Accurate diagnosis and effective treatment of LPR has been challenging. Much research has been dedicated to the elucidation of its complex pathophysiology and the development of accurate diagnostic modalities and effective treatment. Considerable advancements have been made in the evaluation and treatment of LPR. PMID- 22040631 TI - Management of the obese patient with gastroesophageal reflux disease. AB - Obesity and gastroesophageal reflux disease (GERD) are common chronic illnesses. They often coexist and need to be treated concomitantly. Fundoplication may be effective for the short-term control of GERD in the obese patient; however, this procedure does not induce weight loss or treat the comorbid conditions related to obesity. Roux-en-Y gastric bypass is a highly effective treatment of GERD, obesity, and the associated comorbidities. Surgeons who are not comfortable with a bariatric surgical procedure in these patients should either complete appropriate advanced training in bariatric surgery or refer those patients to a qualified surgeon who can offer these options. PMID- 22040632 TI - Diagnosis and management of GERD before and after lung transplantation. AB - The strong association between gastroesophageal reflux disease (GERD) and the development and progression of pulmonary diseases has been suggested, and GERD has been focused on as a potential cause and thus a target for prevention and/or therapy. Because GERD is curable, the proper diagnosis and management of underlying GERD would theoretically improve the outcomes. This article reviews the existing literature and discusses the strategy to manage GERD in patients with end-stage pulmonary diseases before and after lung transplantation. PMID- 22040633 TI - Management of cricopharyngeal dysphagia with and without Zenker's diverticulum. AB - Cricopharyngeal dysphagia and Zenker 's diverticulum result from cricopharyngeal dysfunction, a failure of the upper esophageal sphincter to relax at the initiation of swallowing. The focus of surgical management involves a cricopharyngeal myotomy that is performed by either an open or an endoscopic approach. The endoscopic approach offers faster operating times, a shorter hospital stay, earlier time to oral intake, and lower complication rates, but a role for open cricopharyngeal myotomy remains. PMID- 22040634 TI - Peroral endoscopic myotomy for esophageal achalasia: technique, indication, and outcomes. AB - Peroral endoscopic myotomy (POEM) has been developed as an incisionless, minimally invasive endoscopic treatment intending a permanent cure for esophageal achalasia. The concept of endoscopic myotomy was first reported about 3 decades ago, but the direct incision method through the mucosal layer was not considered to be a safe and reliable approach. A novel method of endoscopic myotomy was developed and established by the authors. In this article, the current techniques, applications, and clinical results of POEM are described. PMID- 22040635 TI - Esophageal preservation in esophageal high-grade dysplasia and intramucosal adenocarcinoma. AB - The management of esophageal high-grade dysplasia (HGD) and intramucosal adenocarcinoma remains controversial. Because lymph node involvement is unlikely in this setting, interest in the treatment strategies for esophageal preservation has grown. Esophageal preservation indicates any endoluminal procedure that is used in an attempt to completely eradicate disease while preserving the anatomic structure of the esophagus. The goal of esophagus-preserving approaches is to provide definitive therapy while avoiding the morbidity of esophagectomy. This article describes the patient selection and the status of currently available esophagus-preserving options, and discusses the strategy for treating HGD and intramusocal adenocarcinoma. PMID- 22040636 TI - Advances in the management of esophageal perforation. AB - Therapy for acute esophageal perforation in the last decade has benefited from newer technology in endoscopy and imaging. Success with nonoperative therapies such as endoluminal stenting and clipping has improved outcomes and shortened length of stay in selected patients. Iatrogenic injury currently comprises most acute esophageal perforation, and nonoperative therapy may be appropriate in a significant percentage of patients. The decision regarding operative vs non operative therapy is best done by a dedicated surgical team with experience in all the surgical and endoscopic treatment options. Boerhaave syndrome occurs less often and may be treated with endoscopic therapy, although it more likely requires operative intervention. This article reviews current advances in the diagnosis and management of acute esophageal perforation. PMID- 22040637 TI - New pharmacologic approaches in gastroesophageal reflux disease. AB - This article highlights current and emerging pharmacological treatments for gastroesophageal reflux disease (GERD), opportunities for improving medical treatment, the extent to which improvements may be achieved with current therapy, and where new therapies may be required. These issues are discussed in the context of current thinking on the pathogenesis of GERD and its various manifestations and on the pharmacologic basis of current treatments. PMID- 22040638 TI - The natural history and complications of eosinophilic esophagitis. AB - Eosinophilic esophagitis is a chronic disease limited to the esophagus and has a persistent or spontaneously fluctuating course. So far it does not seem to limit life expectancy, but it often substantially impairs the quality of life. To date, there has been no association with malignant conditions, but there is concern that the chronic, uncontrolled inflammation will evoke irreversible structural alterations of the esophagus, leading to tissue fibrosis, stricture formation, and impaired function. This esophageal remodeling may result in several disease inherent and procedure-related complications. PMID- 22040640 TI - [Usefulness of the new Spectral-Domain Optical Coherence Tomography (SD-OCT) devices in the study of degenerative dementias]. PMID- 22040641 TI - [Short-tau inversion-recovery (STIR) sequence magnetic resonance imaging evaluation of orbital structures in Graves' orbitopathy]. AB - OBJECTIVE: To evaluate the orbital structures and to establish correlations with disease activity and severity in patients with Graves' hyperthyroidism and orbitopathy (GO) using short-tau inversion-recovery (STIR) sequence magnetic resonance imaging (MRI). METHODS: Observational, cross-sectional, case-control study. Twenty-eight patients with euthyroid status after treatment and GO (GO group) and 15 control subjects (control group) were included. Patients underwent a complete ophthalmologic examination and were then assessed according to the EUGOGO (European Group on Graves' Orbitopathy) recommendations. Muscle cross sectional areas, orbital tissue volumes and the signal intensity ratio (SIR) from the most inflamed extraocular muscle were calculated using a STIR-T2 weighted sequence MRI. Correlations between clinical and MRI measurements were analyzed. RESULTS: Enlargements in the cross-sectional areas and volumes were significant for most EOMs (P<.001), but not for the lateral rectus muscle cross-sectional area. A significant difference in SIR values between patients with GO and control subjects (P<.001) was found. No significant correlations were found between muscle cross-sectional areas, orbital tissue volumes, SIR values and the clinical activity parameters. CONCLUSIONS: Given the small sample size of our study, with the obvious need for larger clinical trials, we were unable to demonstrate that the STIR sequences in MRI are a sensitive tool in assessing patients with longstanding GO in order to detect inflammatory changes and activity follow-up, possibly because it is in inactive phase. Meanwhile, it is still necessary to continue performing a thorough clinical evaluation in the therapeutic management of GO. PMID- 22040642 TI - [Horizontal sensory strabismus: characteristics and treatment results]. AB - PURPOSE: To study the types of horizontal sensory strabismus, their causes, and treatment outcomes. METHODS: A retrospective analysis of 44 patients with horizontal sensory strabismus who were treated from 2002 to 2007. Patients whose worse eye vision was inferior or equal to 0.2 were included. The deviation angle in primary position, causes, type of treatment, and pre-operative or post operative diplopia were studied. A good result was considered if the final deviation was less than 10 prism diopters (pd). RESULTS: Of the patients studied, 63.6% had exotropia and the 36.4% had esotropia. The visual acuity was between 0.1 and no light perception in 75% of patients. The causes responsible for low vision were congenital in 28, and acquired in 16 cases. The mean deviation was 46.7 pd. Diplopia was present in 5 cases, which were resolved with surgical treatment in 3 of them. The eye with reduced vision was operated on in 37 patients, both eyes in 6 cases, and botulinum toxin was injected in 1 case. The final outcome was successful in 90.6% of the cases which were surgically treated. The mean follow up was 31.84 months. CONCLUSIONS: There were twice as many exotropias as esotropias. Strabismus surgery of the amblyopic eye shows excellent results without the need of new operations. There were no new diplopia cases. PMID- 22040643 TI - [Effects of encircling scleral buckling on the morphology and biomechanical properties of the cornea]. AB - OBJECTIVE: To investigate the effects of encircling scleral buckle (SB) on corneal biomechanical properties of the cornea and its morphological parameters. METHODS: We prospectively examined twelve eyes diagnosed with vitreous haemorrhage undergoing pars plana vitrectomy (PPV), and fifteen eyes undergoing combined PPV and scleral buckle (PPV/SB) for repair of rhegmatogenous retinal detachment (RRD). Corneal biomechanical properties, including corneal hysteresis (CH) and corneal resistance factor (CRF), were measured with an Ocular Response Analyser (ORA) before and 1-month postoperatively. The ORA also determined the values of intraocular pressure (IOPg) and corneal compensated IOP (IOPcc). Finally, four morphological parameters of the cornea were measured with the Orbscan II topographer (Orbtek, Inc.): mean corneal power, thinnest corneal point (MUm), and anterior chamber depth (ACD). RESULTS: CH decreased significantly from 10.2+/-1.7mmHg to 7.6+/-1.1mmHg after PPV/SB (p=0.003), but not after PPV alone (9.8+/-3.2mmHg vs 11.6+/-2.7mmHg, P=.465). CRF did not change significantly after surgery in both groups. IOPg and IOPcc increased significantly in the PPV/SB group (P=.019 and P=.010, respectively) but not in PPV group (P=.715 and P=.273, respectively). Unlike the PPV group, values were significantly higher than IOPg values before (P=.001) and after surgery (P=.003) in the PPV/SB group IOPcc. Neither the PPV/SB group nor the PPV group showed any significant changes in the corneal morphological parameters after surgery (P>.05). CONCLUSIONS: SB surgery leads to a change in the corneal biomechanical properties without altering corneal morphological parameters. It may cause an underestimation error in IOP measurement. PPV may be a less invasive surgical approach for the repair of noncomplex RRD than PPV/SB. PMID- 22040644 TI - [Diode laser photocoagulation of retinopathy of prematurity]. AB - OBJECTIVE: To describe diode laser photocoagulation results in retinopathy of prematurity (ROP) in our hospital. MATERIAL AND METHOD: Retrospective cross sectional study based on clinical histories of the premature infants treated during the period from 2004 to 2008. RESULTS: In the treated group we found a predominance of pre-threshold retinopathy versus threshold retinopathy (84.35% vs 15.65%). The anatomic results were good in 96.5% of 147 eyes. None of the treated eyes in pre-threshold stage showed a poor result. Nine months after treatment, 84.85% of 132 eyes showed good functional results. A poor visual response was associated in most of the cases with neurological diseases. Infants with intraventricular haemorrhages had the worst anatomical and functional results. Strabismus (23.5%) and nystagmus (10.3%) rates were high, probably due to the increased prevalence of neurological diseases. The mortality rate in treated children was 7.3%. CONCLUSIONS: Diode laser photocoagulation in ROP offers very good anatomical results when performed at the appropriate time. Nevertheless, prematurity is still a very important cause of visual dysfunction in infancy due to the associated neurological disturbances. PMID- 22040645 TI - [Effectiveness of topical bevacizumab in bilateral primary lipid keratopathy]. AB - CASE REPORT: A 75-year-old man with bilateral idiopathic lipid keratopathy underwent a penetrating keratoplasty in the left eye. One month later, there was deep corneal neovascularisation extending across the bed and the graft-host interface, with a whitish opacity surrounding the vessels. Topical bevacizumab (25mg/mL) was administered 4 times daily for 2 months with partial regression of corneal neovascularization. DISCUSSION: Topical bevacizumab may be useful in preventing a recurrence of lipid deposition after penetrating keratoplasty in patients with bilateral primary lipid keratopathy, although its long-term efficacy needs to be assessed. PMID- 22040646 TI - [Horner syndrome as a manifestation of carotid artery dissection]. AB - CLINICAL CASE: A 42-year-old man presented with ptosis and miosis in his left eye and a history of headache over the last 20 days. An angioresonance showed dissection of internal carotid artery. DISCUSSION: "Painful Horner's Syndrome" is considered to be a medical emergency due possible onset of an internal carotid artery dissection. We consider that awareness of neuro-ophthalmologic emergencies is very important in the clinical praxis of an ophthalmologist. Multidisciplinary treatment and follow-up of these patients is required. PMID- 22040647 TI - [Use of intravitreal bevacizumab for the treatment of choroidal neovascularization secondary to choroidal rupture]. AB - CASE REPORT: A 28 year-old male attended our Emergency Department with a traumatic choroidal rupture and macular haemorrhage. After pneumatic displacement of the haemorrhage with C(3)F(8) and tissue plasminogen activator, the haemorrhage was reabsorbed and visual acuity (VA) improved. Three months later the patient presented with decreased VA and a juxtafoveal choroidal neovascularisation (CNV) that was treated with intravitreal bevacizumab. One year after a single bevacizumab injection the CNV remained inactive, with a final VA of 0.5. DISCUSSION: Intravitreal bevacizumab injection is a new and effective treatment for traumatic CNV. In our patient, in contrast to other aetiologies, the CNV needed no more than one Avastin((r)) injection to be inactivated, after one year of follow-up. PMID- 22040648 TI - [Francesco Giamberti's temporal arteritis? Eye pathology in the paintings of Piero di Cosimo]. PMID- 22040649 TI - The Jinniushan hominin pedal skeleton from the late Middle Pleistocene of China. AB - Bipedalism has long been recognized as the seminal adaptation of the hominin radiation and thus used to distinguish hominins from great ape fossils. Notwithstanding preconceptions and varied interpretations, the distinctive features of the modern human foot and accompanying striding gait, appear to be recent innovations that are largely absent in the earliest facultative bipeds. These distinctive features are mainly components of fixed longitudinal and transverse pedal arches, and of a uniquely derived hallucal metatarsophalangeal joint. They enhance ankle joint plantar flexor function and accommodate localized peak plantar pressures at the medial ball during terminal stance. To date, the paleontological record has yielded very little of the hominin foot, especially of the Middle Pleistocene hominins. New specimens from this time interval should help provide insights into the timing and pattern of what appears to be a mosaic pattern of evolution of the modern human foot features. Here we describe the fossil hominin foot skeleton recovered from the Jinniushan site, Liaoning Province, People's Republic of China. It affords a singular glimpse of the pedal morphology of a late Middle Pleistocene hominin (c.f. Homo heidlebergensis). Dated to 200ka or older, this foot offers the earliest evidence for increased stability of the medial longitudinal arch, while retaining a number of primitive features apparently characteristic of robust premodern hominins, including lower arches and a less stable hallucal metatarsophalangeal joint (medial ball) than in modern humans. These features reflect different foot capabilities and suggest the bipedal stride of the Jinniushan hominin differed subtlety from that of modern humans. PMID- 22040650 TI - Sparse signal representation and its applications in ultrasonic NDE. AB - Many sparse signal representation (SSR) algorithms have been developed in the past decade. The advantages of SSR such as compact representations and super resolution lead to the state of the art performance of SSR for processing ultrasonic non-destructive evaluation (NDE) signals. Choosing a suitable SSR algorithm and designing an appropriate overcomplete dictionary is a key for success. After a brief review of sparse signal representation methods and the design of overcomplete dictionaries, this paper addresses the recent accomplishments of SSR for processing ultrasonic NDE signals. The advantages and limitations of SSR algorithms and various overcomplete dictionaries widely-used in ultrasonic NDE applications are explored in depth. Their performance improvement compared to conventional signal processing methods in many applications such as ultrasonic flaw detection and noise suppression, echo separation and echo estimation, and ultrasonic imaging is investigated. The challenging issues met in practical ultrasonic NDE applications for example the design of a good dictionary are discussed. Representative experimental results are presented for demonstration. PMID- 22040651 TI - Quantification of hydroxyprolyl-glycine (Hyp-Gly) in human blood after ingestion of collagen hydrolysate. AB - Plasma levels of prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp Gly) in healthy volunteers (n=5) after ingestion of collagen hydrolysate were estimated by liquid chromatography-tandem mass spectrometry. The ratio of Hyp-Gly to Pro-Hyp was distributed in the range of 0.063-0.221. This is a first report for quantification of food-derived Hyp-Gly in human plasma. PMID- 22040652 TI - Heart disease among adults exposed to the September 11, 2001 World Trade Center disaster: results from the World Trade Center Health Registry. AB - OBJECTIVE: To examine associations between 9/11-related exposures, posttraumatic stress disorder (PTSD), and subsequent development of heart disease (HD). METHODS: We prospectively followed 39,324 WTC Health Registry participants aged >=18 on 9/11 for an average of 2.9 years. HD was defined as self-reported physician-diagnosed angina, heart attack, and/or other HD reported between study enrollment (2003-2004) and a follow-up survey (2006-2008) in enrollees without previous HD. A PTSD Checklist (PCL) score >=44 was considered PTSD. We calculated adjusted hazard ratios (AHR) and 95% confidence intervals (CI) to examine relationships between 9/11-related exposures and HD. RESULTS: We identified 1162 HD cases (381 women, 781 men). In women, intense dust cloud exposure was significantly associated with HD (AHR 1.28, 95% CI 1.02-1.61). Injury on 9/11 was significantly associated with HD in women (AHR 1.46, 95% CI 1.19-1.79) and in men (AHR 1.33, 95% CI 1.15-1.53). Participants with PTSD at enrollment had an elevated HD risk (AHR 1.68, 95% CI 1.33-2.12 in women, AHR 1.62, 95% CI 1.34-1.96 in men). A dose-response relationship was observed between PCL score and HD risk. CONCLUSION: This exploratory study suggests that exposure to the WTC dust cloud, injury on 9/11 and 9/11-related PTSD may be risk factors for HD. PMID- 22040653 TI - Integrating levels of complexity: a trend in developmental biology. PMID- 22040654 TI - Steady-state kinetic mechanism of the proline:ubiquinone oxidoreductase activity of proline utilization A (PutA) from Escherichia coli. AB - The multifunctional proline utilization A (PutA) flavoenzyme from Escherichia coli performs the oxidation of proline to glutamate in two catalytic steps using separate proline dehydrogenase (PRODH) and Delta(1)-pyrroline-5-carboxylate (P5C) dehydrogenase domains. In the first reaction, the oxidation of proline is coupled to the reduction of ubiquinone (CoQ) by the PRODH domain, which has a beta(8)alpha(8)-barrel structure that is conserved in bacterial and eukaryotic PRODH enzymes. The structural requirements of the benzoquinone moiety were examined by steady-state kinetics using CoQ analogs. PutA displayed activity with all the analogs tested; the highest k(cat)/K(m) was obtained with CoQ(2). The kinetic mechanism of the PRODH reaction was investigated use a variety of steady state approaches. Initial velocity patterns measured using proline and CoQ(1), combined with dead-end and product inhibition studies, suggested a two-site ping pong mechanism for PutA. The kinetic parameters for PutA were not strongly influenced by solvent viscosity suggesting that diffusive steps do not significantly limit the overall reaction rate. In summary, the kinetic data reported here, along with analysis of the crystal structure data for the PRODH domain, suggest that the proline:ubiquinone oxidoreductase reaction of PutA occurs via a rapid equilibrium ping-pong mechanism with proline and ubiquinone binding at two distinct sites. PMID- 22040656 TI - [Should treatment of Achilles tendon rupture be changed?]. PMID- 22040655 TI - Nek family of kinases in cell cycle, checkpoint control and cancer. AB - Early studies in lower Eukaryotes have defined a role for the members of the NimA related kinase (Nek) family of protein kinases in cell cycle control. Expansion of the Nek family throughout evolution has been accompanied by their broader involvement in checkpoint regulation and cilia biology. Moreover, mutations of Nek family members have been identified as drivers behind the development of ciliopathies and cancer. Recent advances in studying the physiological roles of Nek family members utilizing mouse genetics and RNAi mediated knockdown are revealing intricate associations of Nek family members with fundamental biological processes. Here, we aim to provide a comprehensive account of our understanding of Nek kinase biology and their involvement in cell cycle, checkpoint control and cancer. PMID- 22040657 TI - [Promising conservative treatment using dynamic mobilisation after Achilles tendon rupture]. AB - There is no consensus regarding the optimal treatment of acute Achilles tendon ruptures. This review of the literature on the subject shows a significantly higher rate of reruptures (RR) in the conservatively treated group compared to the surgically treated group when the foot is immobilised in the aftertreatment. Recent studies that used early dynamic mobilisation in the conservatively treated group did not show this difference in the RR rate. The latest literature on the subject indicates that non-operative treatment, followed by dynamic aftertreatment, results in the lowest complication rate and a good functional outcome. PMID- 22040658 TI - [Coronary angiography should be considered after out-of-hospital cardiac arrest]. AB - Cardiac arrest has a poor prognosis. Ischaemic heart disease is the main cause of out-of-hospital cardiac arrest. This paper is a review of the essential studies on acute coronary angiography and angioplasty in post resuscitation care. No randomised studies were found. Observational studies support the use of acute angiography in ST-segment elevation myocardial infarction. The negative predictive value of ST-segment elevation can be low after out-of-hospital cardiac arrest, and acute angiography should be considered regardless of electrocardiographic findings. PMID- 22040659 TI - [Rater bias in postgraduate medical education]. AB - In-training assessment is a cornerstone in outcome based postgraduate medical education. When assessing the trainee the trainer should be aware of potential pitfalls and biases and how to avoid these. This paper summarises assessor biases and pitfalls and gives recommendations on how to avoid these. PMID- 22040660 TI - [Spinal manipulation for chronic low back pain--a survey of a chronic review]. AB - A new Cochrane review based on 26 studies - 18 new since the last Cochrane review from 2003 - on spinal manipulation for chronic low back pain has been published by Rubinstein et al. Generally, manipulation for these patients was not clinically relevant better than other treatments like e.g. physical training. In general, the widespread use of manipulation should be reduced. The issues of specific subgroups with possible relevance/irrelevance of such treatment to obtain short-lasting pain relief in selected cases are discussed. PMID- 22040661 TI - [The personal electronic medicine profile contributes to the avoidance of wrong medication at transfer from primary to secondary sector]. AB - INTRODUCTION: It is a well-known phenomenon that there is a lack of information about patients' medicines at their admittance to hospital. By using data from the electronic medicine profile (PEM) the extra information is to be evaluated and compared to normal procedure for collecting medicine information. MATERIAL AND METHODS: This cross-section investigation involves patients admitted with acute hip fractures at Amager Hospital, Copenhagen. After registration of the patients' medication history extra information was extracted from PEM with the consent of the patient. Information from medication history, patient, general practitioner, and PEM was compared in order to reach an overall view of the patients' current medicine status. RESULTS: Sixty-three patients participated; 58 gave consent. The average age was 80 years, and the patients used on average five medicaments each, totalling 323 out of which PEM stated the use of 99, which were not supplied by other sources. Out of 39 patients 2.5 lacked medicaments. 55% of these medicaments were estimated to be of significant clinical importance for further treatment. Two patients could have been exposed to a potential lethal occurrence had information from PEM not been applied. Every third drug that PEM added belonged to the Anatomical Therapeutic Chemical-systemets group N, which has the indication for the nervous system, including pain and depression. CONCLUSION: Information from PEM helps improve medication history. The possibility of wrong medication especially in the form of insufficient medication and interaction due to lack of information on the patients' current medicine is minimised through the use of PEM. PMID- 22040662 TI - [Biliary papillomatosis is a rare cause of intermittent obstructive icterus]. AB - Over a five-year period a 67 year-old male had been experiencing recurring bouts of biliary obstruction with occasional superimposed cholangitis. Renewed endoscopic retrograde cholangiopancreatography revealed amorphous filling defects and excessive mucinous discharge from the papilla of Vater. Subsequent choledochoscopy demonstrated exophytic papillomatous lesions in the common and left hepatic bile duct. An extended left hemihepatectomy and resection of the common hepatic bile duct was performed. Histological examination revealed biliary papillomatosis - a rare lesion believed to be premalignant. PMID- 22040663 TI - [Eosinophilic myocarditis and sudden unexpected death in a younger patient treated with antipsychotics]. AB - A 36 year-old man suffering from schizophrenia was found dead in his apartment. Forensic autopsy was performed due to sudden unexpected death but did not yield the cause of death. Histological examination of the heart showed eosinophilic myocarditis (EM) while forensic chemistry showed a raised level of aripripazol. We discuss the risk of sudden cardiac death in patients receiving antipsychotic drugs and the possible connection between raised drug levels and EM, and we emphasise the importance of autopsy and hope for better means in the future of finding patients at risk. PMID- 22040664 TI - [Gastrointestinal bleeding and intussusception caused by Peutz-Jeghers syndrome]. AB - Peutz-Jeghers syndrome (PJS) is an inherited, autosomal dominant disorder characterised by haematomatous polyps in the gastrointestinal tract and mucocutaneus hyperpigmentation. A girl 15 years of age presented with microcytic, hypochrome anaemia. Endoscopy revealed several polyps in the stomach and colon. The patient was later operated due to an intussusception from polyps in the jejunum. Histology proved the polyps to be haematomatous as seen in PJS. Patients with PJS have an increased risk of developing both gastrointestinal and extra gastrointestinal cancers. Screening recommendation for PJS is outlined. PMID- 22040665 TI - [Large fibrovascular polyp in the oesophagus]. AB - We describe a 45 year-old man with a fibrovascular polyp attached to the entrance of the oesophagus. The patient had a history with regurgitation of polypose foreign body 4-5 years ago with spontaneous remission. Later the patient developed dysphagia, chest pain and weight loss. Gastroscopy revealed a large polyp in the oesophagus and biopsies showed no malignancy. Excision was intended to be performed endoscopically, but due to size, risk of bleeding and recurrence the operation was changed to a transcervical procedure. After one week the patient could eat and drink normally. PMID- 22040666 TI - [Picture of the month: retroperitoneal abscess]. PMID- 22040667 TI - Optineurin with amyotrophic lateral sclerosis-related mutations abrogates inhibition of interferon regulatory factor-3 activation. AB - Optineurin has been shown to be involved in primary open-angle glaucoma. We recently found that optineurin is involved in familial amyotrophic lateral sclerosis (ALS). On the other hand, optineurin has been shown to inhibit transcription factors related to innate immunity such as NF-kappaB and interferon regulatory factor-3 (IRF3). In the present study, the effect of ALS-associated optineurin mutations on IRF3 activation was investigated. Optineurin inhibited IRF3 activation induced by melanoma differentiation-associated gene 5 or Toll-IL 1 receptor domain-containing adaptor-inducing interferon-beta. The inhibition was abrogated by mutations related to ALS but not by a mutation related to glaucoma. Reporter assay indicated that the JAK-STAT signaling pathway was not affected by optineurin. These results show that ALS-related optineurin is involved in the IRF3 activation pathway. Pathogenesis of ALS may be associated with some kind of innate immunity, especially that against virus infection, through IRF3 activation. PMID- 22040668 TI - Impact of exercise on mitochondrial transcription factor expression and damage in the striatum of a chronic mouse model of Parkinson's disease. AB - The etiology of neurodegenerative disorders like Parkinson's disease remains unknown, although many genetic and environmental factors are suggested as likely causes. Neuronal oxidative stress and mitochondrial dysfunction have been implicated as possible triggers for the onset and progression of Parkinson's neurodegeneration. We have recently shown that long-term treadmill exercise prevented neurological, mitochondrial and locomotor deficits in a chronic 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid-induced mouse model of Parkinson's disease that was originally established in our laboratory. In the present study, we further demonstrated that long-term exercise attenuated both cytochrome c release and elevated levels of p53, which are known to be associated with mitochondrial dysfunction in the striatum of this chronic model. On the other hand, the expressions of mitochondrial transcription factor A and peroxisome proliferator-activated receptor gamma coactivator 1alpha were unexpectedly upregulated in the striatum of this chronic model, but long-term exercise training brought their levels down closer to normal. Our findings suggest that maintaining normal mitochondrial function is essential for preventing the process of Parkinson's disease-like neurodegeneration, whereas stimulating the mitochondrial transcription factors for biogenesis is not obligatory. PMID- 22040669 TI - Edaravone, a free radical scavenger, attenuates behavioral deficits following transient forebrain ischemia by inhibiting oxidative damage in gerbils. AB - The present study investigates the neurological protective effects of edaravone against global brain ischemia. Gerbils were treated with edaravone (3mg/kg; i.p.) 30min before transient forebrain ischemia, which was induced by occluding the bilateral common carotid artery for 5min. The effects of edaravone were examined by measuring neuronal damage and behavioral deficits. Hexanoyl-lysine adduct (HEL) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), oxidative stress markers, were also examined to assess the anti-oxidative effects of edaravone. Edaravone treatment significantly inhibited both lipid and DNA oxidative damage 72h after ischemia, and decreased neuronal damage. Edaravone also significantly reduced the locomotor activity deficit 72h after ischemia and improved memory impairment. These findings suggest that edaravone inhibits oxidative stress and attenuates neuronal damage induced by transient forebrain ischemia in gerbils and which may contribute to improvements in behavioral deficits. PMID- 22040670 TI - Regulatory effects of costunolide on dopamine metabolism-associated genes inhibit dopamine-induced apoptosis in human dopaminergic SH-SY5Y cells. AB - Parkinson's disease (PD) is characterized by the selective loss of dopaminergic (DAergic) neurons in the substantia nigra and the subsequent depletion of dopamine (DA). This study assessed the protective effects of costunolide on DA induced apoptosis in human DAergic SH-SY5Y cells, and its regulation of DA metabolism-associated gene and protein expression. Annexin V and propidium iodide (PI) staining using flow cytometric analysis (FACS) revealed that costunolide significantly protected human DAergic SH-SY5Y cells against DA-induced apoptosis. In addition, co-treatment of costunolide with DA in SH-SY5Y cells regulated DA metabolism-associated gene expression, as we observed an increase in both mRNA and protein levels of nuclear receptor related-1 (Nurr1), DA transporter (DAT), and vesicular monoamine transporter type 2 (VMAT2). In contrast, alpha-synuclein (ASYN) protein levels were decreased. Our findings suggest that costunolide has anti-apoptotic activity, presumably due to its regulatory effects on DA metabolism-associated genes. Therefore, costunolide could be considered as a candidate therapy for the treatment of Parkinson's disease. PMID- 22040671 TI - Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the upregulation of glucose uptake after subsequent reoxygenation in brain endothelial cells. AB - During stroke the blood-brain barrier (BBB) is damaged which can result in vasogenic brain edema and inflammation. The reduced blood supply leads to decreased delivery of oxygen and glucose to affected areas of the brain. Oxygen and glucose deprivation (OGD) can cause upregulation of glucose uptake of brain endothelial cells. In this letter, we investigated the influence of MK801, a non competitive inhibitor of the NMDA-receptor, on the regulation of the glucose uptake and of the main glucose transporters glut1 and sglt1 in murine BBB cell line cerebEND during OGD. mRNA expression of glut1 was upregulated 68.7-fold after 6h OGD, which was significantly reduced by 10MUM MK801 to 28.9-fold. Sglt1 mRNA expression decreased during OGD which was further reduced by MK801. Glucose uptake was significantly increased up to 907% after 6h OGD and was still higher (210%) after the 20h reoxygenation phase compared to normoxia. Ten micromolar MK801 during OGD was able to reduce upregulated glucose uptake after OGD and reoxygenation significantly. Presence of several NMDAR subunits was proven on the mRNA level in cerebEND cells. Furthermore, it was shown that NMDAR subunit NR1 was upregulated during OGD and that this was inhibitable by MK801. In conclusion, the addition of MK801 during the OGD phase reduced significantly the glucose uptake after the subsequent reoxygenation phase in brain endothelial cells. PMID- 22040672 TI - Unchanged expression of the ceramide transfer protein in the acute 6-OHDA neurodegenerative model. AB - Ceramides are lipids that are abundant in brain tissue where they have an important structural role in cellular membranes. Ceramides are also powerful intracellular signalling molecules controlling cell death, growth and differentiation. So far, the ceramide transfer protein (CERT), a shorter splice variant of the Goodpasture antigen-binding protein (GPBP), is the only known protein with the ability to shuttle ceramide from the endoplasmic reticulum to the Golgi apparatus. GPBP/CERT are widely distributed in the central nervous system where they act as key factors for normal brain development and homeostasis. Ceramide accumulates in neurons during acute neurodegeneration. The objective of this study was to define whether levels of the ceramide transfer protein GPBP/CERT are altered in the acute neurodegenerative process. We used design-based stereology to quantify the number of GPBP/CERT immunoreactive cells in the striatum of 6-hydroxydopamine (6-OHDA) lesioned rats as an animal model of Parkinson's disease (PD). In addition, gray value measurement was performed to quantify GPBP/CERT immunoreactivity-levels within individual cells. No difference in the striatal expression levels of GPBP/CERT proteins was found between diseased and control animals, suggesting that the expression pattern of GPBP/CERT in the striatum is not affected in the 6-OHDA rat model of PD. PMID- 22040673 TI - Neuronal activity reflecting progression of trials in the pre-supplementary motor area of macaque monkey: an expression of neuronal flexibility. AB - We studied the activity of single neurons in the pre-supplementary motor area (pre-SMA) of macaque monkeys as they performed two visuomotor tasks, called the visual fixation task and the visual fixation-blink task. Both tasks involved a sequence of three visual stimuli, red followed by yellow and green. The tasks differed in that the latter one had a gap within the period of the red stimulus, called a "blink". The tasks were performed in two modes, one of which included movements of both the arm and eye and the other of which involved only eye movements. In the arm-eye mode, the monkeys had to press a bar and fixate the red stimulus that appeared after bar press. To receive a reward, both the bar press and visual fixation had to be maintained until the green stimulus triggered bar release. In the eye mode, bar press and bar release were eliminated from the task. Of the 42 neurons active during the visual fixation task, 15 showed task related activity in both arm-eye and eye modes, and our analysis focused on these cells. We found that the introduction of the blink in visual fixation-blink task abolished the task-related activity of these cells over the course of 2-4 trials. This finding suggests a role for the pre-SMA in reflecting progression of trials as an updating of motor instruction. PMID- 22040674 TI - Pneumosinus dilatans, pneumocoele or air cyst? A case report and literature review. AB - BACKGROUND: Pathological paranasal sinus expansion secondary to air is uncommon. However, this condition may be symptomatic or cosmetically apparent, requiring surgical intervention. Various terms have been used to describe this condition, and nomenclature is controversial. METHOD: An 18-year-old man presented with right facial pain, and was subsequently found to have pneumosinus dilatans of the maxillary sinus. A search was conducted of the PubMed, Medline and Embase databases, using the key words 'pneumosinus dilatans', 'pneumoc(o)ele', 'pneumatoc(o)ele' and 'maxillary sinus'. Articles were also hand-searched. Relevant articles published in English were reviewed. RESULTS: The literature review identified 36 cases involving the maxillary sinus (including the present case), with 19 cases reported as pneumosinus dilatans, 12 as pneumocoeles, two as pneumatocoeles, two as pneumosinus dilatans multiplex and one as an air cyst. However, based on the strict classification described by Urken et al., the majority of these cases should be reclassified as pneumocoeles. CONCLUSION: Whilst the nomenclature of this pathology is confusing, distinctions of terminology do not alter the management. Hence, we support the use of the term 'air cyst', to incorporate all these lesions. PMID- 22040675 TI - In vivo innate immune responses of groper (Polyprion oxygeneios) against Miamiensis avidus infection and lack of protection following dietary vitamin C administration. AB - Scuticociliates are extracellular histophagous parasites that affect farmed fish worldwide. One of the most common pathogenic species is Miamiensis avidus, a pathogen of New Zealand groper (Polyprion oxygeneios). The aim of this study was to characterise both the host (groper)-parasite (M. avidus) immune interactions and the possible protective role of dietary sodium ascorbate. Head-kidney leucocytes (HKLs) from naturally infected adult groper showed decreased respiratory burst response and peroxidase (Px) levels than healthy individuals. Infected groper also had significantly higher serum Px levels compared to controls. Myeloperoxidase (MPO) was inhibited in the head-kidney (HK) whereas MPO(+) cells were observed in the skin and muscle lesions. The inhibition of the innate immune responses was further studied in experimental infections with M. avidus, which confirmed depletion of Px inside leucocytes and marked increases in serum Px in infected individuals. Groper juveniles were fed a diet supplemented with sodium ascorbate (Vitamin C) (2g Kg(-1)) for 21 days and then challenged by subcutaneous injection or immersion exposure with live M. avidus cells. No protection was observed in the sodium ascorbate fed groper compared to the control diet following challenge by either injection or immersion. In vitro assays showed that sodium ascorbate itself results in the inhibition of Px and respiratory burst of groper HKLs, supporting the results obtained in vivo. Our results show that histophagous protozoa such as M. avidus hamper innate immune defences of fish hosts and that dietary sodium ascorbate does not protect groper against experimental infection with this parasite. PMID- 22040676 TI - Direct visualization of pH-dependent evolution of structure and dynamics in microgel suspensions. AB - We use 3D confocal microscopy combined with image analysis and particle tracking techniques to study the structure and dynamics of aqueous suspensions of fluorescently labelled p(NIPAm-co-AAc) microgel particles. By adjusting the pH we can tune the interactions between the microgel particles from purely repulsive near neutral pH, to weakly attractive at low pH. This change in the interaction potential has a pronounced effect on the manner in which the suspensions solidify. We directly follow the evolution of the system after a quench from the liquid state to obtain detailed information on the route to kinetic arrest. At low pH and low concentration, dynamic arrest results mainly from crystallization driven by the attraction between particles; crystal nucleation occurs homogeneously throughout the sample and does not appear to be localized to geometric boundaries. Moreover, the growth of crystals is characterized by nucleation-limited kinetics where a rapid growth of crystal domains takes place after a long concentration-dependent lag time. At low pH and high concentration, relaxation of the suspension is constrained and it evolves only slightly, resulting in a disordered solid. At neutral pH, the dynamics are a function of the particle number concentration only; a high concentration leads to the formation of a disordered soft glassy solid. PMID- 22040677 TI - Mychonastes afer HSO-3-1 as a potential new source of biodiesel. AB - BACKGROUND: Biodiesel is considered to be a promising future substitute for fossil fuels, and microalgae are one source of biodiesel. The ratios of lipid, carbohydrates and proteins are different in different microalgal species, and finding a good strain for oil production remains a difficult prospect. Strains producing valuable co-products would improve the viability of biofuel production. RESULTS: In this study, we performed sequence analysis of the 18S rRNA gene and internal transcribed spacer (ITS) of an algal strain designated HSO-3-1, and found that it was closely related to the Mychonastes afer strain CCAP 260/6. Morphology and cellular structure observation also supported the identification of strain HSO-3-1 as M. afer. We also investigated the effects of nitrogen on the growth and lipid accumulation of the naturally occurring M. afer HSO-3-1, and its potential for biodiesel production. In total, 17 fatty acid methyl esters (FAMEs) were identified in M. afer HSO-3-1, using gas chromatography/mass spectrometry. The total lipid content of M. afer HSO-3-1 was 53.9% of the dry cell weight, and we also detected nervonic acid (C24:1), which has biomedical applications, making up 3.8% of total fatty acids. The highest biomass and lipid yields achieved were 3.29 g/l and 1.62 g/l, respectively, under optimized conditions. CONCLUSION: The presence of octadecenoic and hexadecanoic acids as major components, with the presence of a high-value component, nervonic acid, renders M. afer HSO-3-1 biomass an economic feedstock for biodiesel production. PMID- 22040678 TI - The basic property of Lys385 is important for potentiation of the human alpha1 glycine receptor by ethanol. AB - Ethanol alters the function of several members of the Cys-loop ligand-gated ion channel superfamily. Recent studies have shown that the sensitivity of the alpha1 glycine receptor (GlyR) to ethanol can be affected by the state of G protein activation mediated by the interaction of Gbetagamma with intracellular amino acids in the GlyR. Here, we evaluated the physicochemical property of Lys385 that contributes to ethanol modulation by using mutagenesis, patch-clamp, and biochemical techniques. A conserved substitution (K385R) did not affect either the apparent glycine EC50 (40 +/- 1 versus 41 +/- 0.5 MUM) or the ethanol-induced potentiation (53 +/- 5 versus 46 +/- 5%) of the human alpha1 GlyR. On the other hand, replacement of this residue with glutamic acid (K385E), an acidic amino acid, reduced the potentiation of the GlyR to 10 +/- 1%. Furthermore, mutations with a hydrophobic leucine (K385L), a hydrogen bond donor glutamine (K385Q), or a neutral residue (K385A) also reduced ethanol modulation. Finally, substitution by a large and hydrophobic residue (K385F) and deletion of 385 (Lys385_) reduced ethanol modulation to 10 +/- 4 and 17 +/- 0.4%, respectively. Experiments using dynamic cysteine substitution with a methanethiosulfonate reagent and homology modeling indicate that the basic property and the position of Lys385, probably because of its interaction with Gbetagamma, is critical for ethanol potentiation of the receptor. PMID- 22040679 TI - gamma-Tocotrienol protects against mitochondrial dysfunction and renal cell death. AB - Oxidative stress is a major mechanism of a variety of renal diseases. Tocopherols and tocotrienols are well known antioxidants. This study aimed to determine whether gamma-tocotrienol (GT3) protects against mitochondrial dysfunction and renal proximal tubular cell (RPTC) injury caused by oxidants. Primary cultures of RPTCs were injured by using tert-butyl hydroperoxide (TBHP) in the absence and presence of GT3 or alpha-tocopherol (AT). Reactive oxygen species (ROS) production increased 300% in TBHP-injured RPTCs. State 3 respiration, oligomycin sensitive respiration, and respiratory control ratio (RCR) decreased 50, 63, and 47%, respectively. The number of RPTCs with polarized mitochondria decreased 54%. F0F1-ATPase activity and ATP content decreased 31 and 65%, respectively. Cell lysis increased from 3% in controls to 26 and 52% at 4 and 24 h, respectively, after TBHP exposure. GT3 blocked ROS production, ameliorated decreases in state 3 and oligomycin-sensitive respirations and F0F1-ATPase activity, and maintained RCR and mitochondrial membrane potential (DeltaPsi(m)) in injured RPTCs. GT3 maintained ATP content, blocked RPTC lysis at 4 h, and reduced it to 13% at 24 h after injury. Treatment with equivalent concentrations of AT did not block ROS production and cell lysis and moderately improved mitochondrial respiration and coupling. This is the first report demonstrating the protective effects of GT3 against RPTC injury by: 1) decreasing production of ROS, 2) improving mitochondrial respiration, coupling, DeltaPsi(m), and F0F1-ATPase function, 3) maintaining ATP levels, and 4) preventing RPTC lysis. Our data suggest that GT3 is superior to AT in protecting RPTCs against oxidant injury and may prove therapeutically valuable for preventing renal injury associated with oxidative stress. PMID- 22040680 TI - Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritis. AB - Based on genetic studies that establish the role of spleen tyrosine kinase (Syk) in immune function, inhibitors of this kinase are being investigated as therapeutic agents for inflammatory diseases. Because genetic studies eliminate both adapter functions and kinase activity of Syk, it is difficult to delineate the effect of kinase inhibition alone as would be the goal with small-molecule kinase inhibitors. We tested the hypothesis that specific pharmacological inhibition of Syk activity retains the immunomodulatory potential of Syk genetic deficiency. We report here on the discovery of (4-(3-(2H-1,2,3-triazol-2 yl)phenylamino)-2-((1R,2S)-2-aminocyclohexylamino) pyrimidine-5-carboxamide acetate (P505-15), a highly specific and potent inhibitor of purified Syk (IC50 1 2 nM). In human whole blood, P505-15 potently inhibited B cell antigen receptor mediated B cell signaling and activation (IC50 0.27 and 0.28 MUM, respectively) and Fcepsilon receptor 1-mediated basophil degranulation (IC50 0.15 MUM). Similar levels of ex vivo inhibition were measured after dosing in mice (Syk signaling IC50 0.32 MUM). Syk-independent signaling and activation were unaffected at much higher concentrations, demonstrating the specificity of kinase inhibition in cellular systems. Oral administration of P505-15 produced dose-dependent anti inflammatory activity in two rodent models of rheumatoid arthritis. Statistically significant efficacy was observed at concentrations that specifically suppressed Syk activity by ~67%. Thus specific Syk inhibition can mimic Syk genetic deficiency to modulate immune function, providing a therapeutic strategy in P505 15 for the treatment of human diseases. PMID- 22040681 TI - Relationship between Rgs2 gene expression level and anxiety and depression-like behaviour in a mutant mouse model: serotonergic involvement. AB - RGS2 is a member of a family of proteins that negatively modulate G-protein coupled receptor transmission. Variations in the RGS2 gene were found to be associated in humans with anxious and depressive phenotypes. We sought to study the relationship of Rgs2 expression level to depression and anxiety-like behavioural features, sociability and brain 5-HT1A and 5-HT1B receptor expression. We studied male mice carrying a mutation that causes lower Rgs2 gene expression, employing mice heterozygous (Het) or homozygous (Hom) for this mutation, or wild-type (WT). Mice were subjected to behavioural tests reflecting depressive-like behaviour [forced swim test (FST), novelty suppressed feeding test (NSFT)], elevated plus maze (EPM) for evaluation of anxiety levels and the three-chamber sociability test. The possible involvement of raphe nucleus 5-HT1A receptors in these behavioural features was examined by 8-OH-DPAT-induced hypothermia. Expression levels of 5-HT1A and 5-HT1B receptors in the cortex, raphe nucleus and hypothalamus were compared among mice of the different Rgs2 genotype groups. NSFT results demonstrated that Hom mice showed more depressive like features than Rgs2 Het and WT mice. A trend for such a relationship was also suggested by the FST results. EPM and sociability test results showed Hom and Het mice to be more anxious and less sociable than WT mice. In addition Hom and Het mice were characterized by lower basal body temperature and demonstrated less 8 OH-DPAT-induced hypothermia than WT mice. Finally, Hom and Het mice had significantly lower 5-HT1A and 5-HT1B receptor expression levels in the raphe than WT mice. Our findings demonstrate a relationship between Rgs2 gene expression level and a propensity for anxious and depressive-like behaviour and reduced social interaction that may involve changes in serotonergic receptor expression. PMID- 22040682 TI - TiO2 nanotubes as drug nanoreservoirs for the regulation of mobility and differentiation of mesenchymal stem cells. AB - The extracellular microenvironment plays a key role in the regulation of cellular behavior. To mimic the natural extracellular microenvironment, TiO(2) nanotube (TNT) arrays as drug nanoreservoirs for loading of bone morphogenetic protein 2 (BMP2) were constructed on titanium substrates and then covered with multilayered coatings of gelatin/chitosan (Gel/Chi) for controlled drug release. The multilayered coatings were constructed via a spin-assisted layer-by-layer assembly technique. The successful fabrication of this system was monitored by field emission scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy and contact angle measurements. Multilayered coating with Gel/Chi retained the drug bioactivity and release properties, which were revealed by superoxide dismutase activity measurement. In addition, cytoskeleton observation and wound healing assay confirmed that BMP2-loaded and multilayer coated TNT arrays were able to stimulate motogenic responses of mesenchymal stem cells (MSCs). More importantly, the system demonstrated that it was capable of promoting the osteoblastic differentiation of MSCs. This study may have potential impact on the development of bone implants for enhanced bone osseointegration. PMID- 22040683 TI - Fabrication and in vitro evaluation of the collagen/hyaluronic acid PEM coating crosslinked with functionalized RGD peptide on titanium. AB - Surface modification of titanium (Ti) using biomolecules has attracted much attention recently. In this study, a new strategy has been employed to construct a stable and bioactive coating on Ti. To this end, a derivative of hyaluronic acid (HA), i.e. HA-GRGDSPC-(SH), was synthesized. The disulfide-crosslinked Arg Gly-Asp (RGD)-containing collagen/hyaluronic acid polyelectrolyte membrane (PEM) coating was then fabricated on Ti through the alternate deposition of collagen and HA-GRGDSPC-(SH) with five assembly cycles and subsequent crosslinking via converting free sulphydryl groups into disulfide linkages (RGD-CHC-Ti group). The assembly processes for PEM coating and the physicochemical properties of the coating were carefully characterized. The stability of PEM coating in phosphate buffered saline solution could be adjusted by the crosslinking degree, while its degradation behaviors in the presence of glutathione were glutathione concentration dependent. The adhesion and proliferation of MC3T3-E1 cells were significantly enhanced in the RGD-CHC-Ti group. Up-regulated bone specific genes, enhanced alkaline phosphatase activity and osteocalcin production, the increased areas of mineralization were also observed in the RGD-CHC-Ti group. These results indicate that the strategy employed herein may function as an effective way to construct stable, RGD-containing bioactive coatings on Ti. PMID- 22040684 TI - Surface immobilization of bone morphogenetic protein 2 via a self-assembled monolayer formation induces cell differentiation. AB - Bone extracellular matrix consists of a network of proteins in which growth factors, like bone morphogenetic protein 2 (BMP-2), are embedded and released upon matrix turnover and degradation. Recombinant human (rh)BMP-2 shows promise in enhancing bone fracture repair, although issues regarding finding a suitable delivery system still limit its extensive clinical use. The aim of this study is to determine which cell activities are triggered by the presentation of immobilized rhBMP-2. For this purpose gold surfaces were first decorated with a self-assembled monolayer consisting of a hetero-bifunctional linker. rhBMP-2 was covalently bound to the surfaces via this linker and used to investigate the cellular responses of C2C12 myoblasts. We show that covalently immobilized rhBMP 2 (iBMP-2) initiates short-term signaling events. Using a BMP-responsive reporter gene assay and western blotting to monitor phosphorylation of Smad1/5/8 we prove that iBMP-2 activates BMP-dependent signal transduction. Furthermore, we demonstrate that iBMP-2 suppresses myotube formation and promotes the osteoblast phenotype in C2C12 cells. The bioactivity of surface-bound rhBMP-2 presented in this study is not due to its release into the medium. As such, our simple approach paves the way for the controlled local presentation of immobilized growth factors, limiting degradation while still maintaining biological activity. PMID- 22040685 TI - Copper-releasing, boron-containing bioactive glass-based scaffolds coated with alginate for bone tissue engineering. AB - The aim of this study was to synthesize and characterize new boron-containing bioactive glass-based scaffolds coated with alginate cross-linked with copper ions. A recently developed bioactive glass powder with nominal composition (wt.%) 65 SiO2, 15 CaO, 18.4 Na2O, 0.1 MgO and 1.5 B2O3 was fabricated as porous scaffolds by the foam replica method. Scaffolds were alginate coated by dipping them in alginate solution. Scanning electron microscopy investigations indicated that the alginate effectively attached on the surface of the three-dimensional scaffolds leading to a homogeneous coating. It was confirmed that the scaffold structure remained amorphous after the sintering process and that the alginate coating improved the scaffold bioactivity and mechanical properties. Copper release studies showed that the alginate-coated scaffolds allowed controlled release of copper ions. The novel copper-releasing composite scaffolds represent promising candidates for bone regeneration. PMID- 22040686 TI - Calcium phosphate coatings on magnesium alloys for biomedical applications: a review. AB - Magnesium has been suggested as a revolutionary biodegradable metal for use as an orthopaedic material. As a biocompatible and degradable metal, it has several advantages over the permanent metallic materials currently in use, including eliminating the effects of stress shielding, improving biocompatibility concerns in vivo and improving degradation properties, removing the requirement of a second surgery for implant removal. The rapid degradation of magnesium, however, is a double-edged sword as it is necessary to control the corrosion rates of the materials to match the rates of bone healing. In response, calcium phosphate coatings have been suggested as a means to control these corrosion rates. The potential calcium phosphate phases and their coating techniques on substrates are numerous and can provide several different properties for different applications. The reactivity and low melting point of magnesium, however, require specific parameters for calcium phosphate coatings to be successful. Within this review, an overview of the different calcium phosphate phases, their properties and their behaviour in vitro and in vivo has been provided, followed by the current coating techniques used for calcium phosphates that may be or may have been adapted for magnesium substrates. PMID- 22040687 TI - Structure and properties of bioactive eutectic glasses based on the Ca3(PO4)2 CaSiO3-CaMg(SiO3)2 system. AB - Taking into account the phase equilibrium relationships within the Ca3(PO4)2 CaSiO3-CaMg(SiO3)2 ternary system, three bioactive glasses with a eutectic composition and analogous amounts of Ca3(PO4)2 (~40 wt.%) have been prepared. The structure of the glasses was investigated by 31P and 29Si magic angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopy. The glasses exhibited thermal expansion coefficients (50-600 degrees C) of 11.8-13.3*10(-6) degrees C(-1), a glass transition temperature of 790-720 degrees C and a softening temperature of 811-750 degrees C. The mechanical properties of the glasses were as follows: bending strength ~100 MPa, Young's modulus 94-83 GPa, Vickers microhardness 7.1 4.1 GPa and toughness 0.8 MPa m1/2. The bioactive properties were discussed in terms of their structure deduced by MAS-NMR spectroscopy and the field strength of the network modifiers (Mg2+ and Ca2+). A knowledge of the glass structure was important in predicting its bioactivity. PMID- 22040688 TI - Effective inhibition of the early copper ion burst release with ultra-fine grained copper and single crystal copper for intrauterine device application. AB - To solve the main problems of existing coarse grained copper (CG Cu) intrauterine devices (IUD)-namely burst release and a low transfer efficiency of the cupric ions during usage-ultra-fine grained copper (UFG Cu) and single crystal copper (SC Cu) have been investigated as potential substitutes. Their corrosion properties with CG Cu as a control have been studied in simulated uterine fluid (SUF) under different conditions using electrochemical measurement methods. Long term immersion of UFG Cu, SC Cu and CG Cu samples in SUF at 37 degrees C have been studied for 300 days. A lower copper ion burst release and a higher efficiency release of cupric ions were observed for UFG Cu and SC Cu compared with CG Cu in the first month of immersion and 2 months later. The respective corrosion mechanisms for UFG Cu, SC Cu and CG Cu in SUF are proposed. In vitro biocompatibility tests show a better cellular response to UFG Cu and SC Cu than CG Cu. In terms of instantaneous corrosion behavior, long-term corrosion performance and in vitro biocompatibility, the three pure copper materials follow the order: UFG Cu>SC Cu>CG Cu, which indicates that UFG Cu could be the most suitable candidate material for intrauterine devices. PMID- 22040689 TI - Declining needs for total joint replacements for rheumatoid arthritis. AB - This millennium brings new views to rheumatology. Total joint replacement surgery is needed less often as active treatment strategies combined with availability of new medications has led to more effective rheumatoid arthritis control. This was beautifully shown in a recent issue of Arthritis Research & Therapy by a Swedish study that uses data from national registers and compares incidence rates for total hip and knee arthroplasties before and after the establishment of biologic agents use for rheumatoid arthritis. PMID- 22040690 TI - Antiphospholipid antibodies in patients with persistent Lyme disease symptoms. PMID- 22040691 TI - Cutaneous lupus erythematosus on the elbows: a peculiar localization. AB - BACKGROUND: The presence of lesions limited to the elbows as expression of a cutaneous lupus erythematosus (CLE) is very unusual. OBJECTIVES: To describe the clinical and microscopic characteristics of these lesions, as well as their relationship with the different cutaneous lupus erythematosus subsets. METHODS: Seven cases of CLE with lesions on the elbows, collected from 1998 to 2009, were retrospectively analysed. All patients had a previous or concomitant diagnosis of lupus erythematosus based on other typical skin lesions for each subtype of lupus erythematosus, and they all met clinical and microscopic criteria. RESULTS: Six patients were women with a mean age of 33.8 years. Five cases had been previously diagnosed with CLE (three lupus erythematosus [LE] tumidus, one subacute CLE and one acute CLE). In the other two cases, these lesions were the first manifestation of the disease. The lesions consisted of pruriginous, erythematous papules and plaques with a slightly scaly surface, located on both elbows. Microscopically, in addition to the typical features of CLE, other changes were observed, including alterations in the texture and the staining properties of collagen fibres (five cases), an interstitial histiocytic infiltrate (four cases), eosinophils (one case) and a Churg-Strauss granuloma (one case). CONCLUSIONS: These peculiar lesions located on the elbows should be included in the spectrum of cutaneous manifestations of LE. Their histopathology combines changes of both LE and interstitial granulomatous dermatitis. PMID- 22040692 TI - Enhancing bone healing during distraction osteogenesis with platelet-rich plasma: a novel molecular mechanism. PMID- 22040693 TI - Reverse oblique intertrochanteric femoral fractures treated with the intramedullary hip screw (IMHS). AB - AIMS: Recent studies have recommended the use of cephalo-medullary devices for the treatment of reverse oblique intertrochanteric femoral fractures (Orthopaedic Trauma Association/Arbeitsgemeinschaft fur Osteosynthesefragen, OTA/AO 31-A3). Both the proximal femoral nail (PFN) and the gamma nail (GN) have shown good outcome results but the results of treatment with the intramedullary hip screw (IMHS) have not been reported in the literature. Our aim was to review the outcomes of these unstable fractures treated with the IMHS implant at our institute. METHODS: Between 1999 and 2008, 6724 consecutive hip fractures were treated at our institute. There were 115 reverse oblique intertrochanteric fractures and 63 of these were treated with the IMHS. We retrospectively reviewed clinical and radiological records for these fractures treated with the IMHS. Follow-up duration ranged from 1 to 6 years. RESULTS: Amongst the 63 patients treated with the IMHS, 57 (90.5%) fractures were reduced satisfactorily with one poorly positioned hip screw and one breach of the anterior femoral cortex. The mean operative time was 115 min, 22 patients required a blood transfusion and 20 had postoperative medical complications. The major orthopaedic complications included two cases of malrotation, three nonunions and one traumatic periprosthetic fracture with a total failure rate of 7.9%. There were four cases of distal locking bolts breaking or backing out. The 30-day mortality was 6.5%. CONCLUSION: The clinical and radiological outcomes achieved with the IMHS compare favourably to the results achieved with other cephalo-medullary devices. We consider the long IMHS a good implant for the treatment of these unstable fractures. PMID- 22040694 TI - Accuracy of in situ neck-shaft angle and shortening measurements of the anatomically reduced, varus malreduced and shortened proximal femur: can we believe what we see on the postoperative films? AB - OBJECTIVES: Measuring the neck-shaft angle (NSA) and amount of shortening of the femoral neck on the anterior to posterior (AP) X-ray is important when treating proximal femur fractures. To compensate for proximal femoral external rotation, the X-rays need to be taken with the leg internally rotated, an act that cannot always be performed or verified. This study aims to define the utility of in situ AP X-ray in NSA and shortening measurements. METHODS: Computed tomography (CT) scans of 50 patients undergoing abdominal CT scans were assessed for the in situ rotation of the femoral neck relative to the AP beam. Three proximal femur fracture Sawbones models were made and AP X-rays of the models were taken with changing proximal femur rotation. NSA and shortening were measured on all X-rays. RESULTS: In situ femoral neck rotation averaged 25.4+/-10.6 degrees of external rotation (range, 0.9-51.8 degrees , 80% of measurements less than 35 degrees ). NSA measurements varied less than 5 degrees with less than 35 degrees of rotation in all models, and were always greater than the true value. Femoral neck vertical length (VL) measurement was independent of proximal femur rotation whereas the horizontal length component was found to be highly dependent on the same. CONCLUSIONS: NSA measured on AP X-ray will be accurate to within 5 degrees in 80% of patients with the hip left in situ and in 100% of the patients if the hip is internally rotated 15 degrees . Measurement of significant varus or loss of VL of the femoral neck can be considered accurate regardless of leg rotation at the time of X-rays being taken. PMID- 22040695 TI - Effects of accidental hypothermia on posttraumatic complications and outcome in multiple trauma patients. AB - INTRODUCTION: Accidental hypothermia seems to predispose multiple trauma patients to the development of posttraumatic complications, such as Systemic Inflammatory Response Syndrome (SIRS), sepsis, Multiple Organ Dysfunction Syndrome (MODS), and increased mortality. However, the role of accidental hypothermia as an independent prognostic factor is controversially discussed. The aim of the present study was to evaluate the incidence of accidental hypothermia in multiple trauma patients and its effects on the development of posttraumatic complications and mortality. PATIENTS AND METHODS: Inclusion criteria for patients in this retrospective study (2005-2009) were an Injury Severity Score (ISS) >=16, age >=16 years, admission to our Level I trauma centre within 6h after the accident. Accidental hypothermia was defined as body temperature less than 35 degrees C measured within 2 h after admission, but always before first surgical procedure in the operation theatre. The association between accidental hypothermia and the development of posttraumatic complications as well as mortality was investigated. Statistical analysis was performed with chi(2)-test, Student's t-test, ANOVA and logistic regression. Statistical significance was considered at p<0.05. RESULTS: 310 multiple trauma patients were enrolled in the present study. Patients' mean age was 41.9 (SD 17.5) years, the mean injury severity score was 29.7 (SD 10.2). The overall incidence of accidental hypothermia was 36.8%. The overall incidence of posttraumatic complications was 77.4% (SIRS), 42.9% (sepsis) and 7.4% (MODS), respectively. No association was shown between accidental hypothermia and the development of posttraumatic complications. Overall, 8.7% died during the posttraumatic course. Despite an increased mortality rate in hypothermic patients, hypothermia failed to be an independent risk factor for mortality in multivariate analysis. CONCLUSIONS: Accidental hypothermia is very common in multiply injured patients. However, it could be assumed that the increase of mortality in hypothermic patients is primarily caused by the injury severity and does not reflect an independent adverse effect of hypothermia. Furthermore, hypothermia was not shown to be an independent risk factor for posttraumatic complications. PMID- 22040696 TI - Chaperoning alpha7 neuronal nicotinic acetylcholine receptors. AB - The alpha7 subtype of nicotinic acetylcholine receptors (AChRs) is one of the most abundant members of the Cys-loop family of receptors present in the central nervous system. It participates in various physiological processes and has received much attention as a potential therapeutic target for a variety of pathologies. The importance of understanding the mechanisms controlling AChR assembly and cell-surface delivery lies in the fact that these two processes are key to determining the functional pool of receptors actively engaged in synaptic transmission. Here we review recent studies showing that RIC-3, a protein originally identified in the worm Caenorhabditis elegans, modulates the expression of alpha7 AChRs in a subtype-specific manner. Potentiation of AChR expression by post-transcriptional events is also critically assessed. PMID- 22040697 TI - Leptin as an immunomodulator. AB - Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. In humans, leptin influences energy homeostasis and regulates neuroendocrine function primarily in states of energy deficiency. Initially described as an antiobesity hormone, leptin has subsequently been shown also to influence basal metabolism, hematopoiesis, thermogenesis, reproduction, and angiogenesis. As a cytokine, leptin can affect thymic homeostasis and the secretion of acute-phase reactants such as interleukin 1 (IL-1) and tumor-necrosis factor-alpha (TNF-alpha). Leptin links nutritional status and proinflammatory T helper 1 (Th1) immune responses and the decrease in leptin plasma concentration during food deprivation leads to impaired immune function. Similar to other pro-inflammatory cytokines, leptin promotes Th1-cell differentiation and can modulate the onset and progression of autoimmune responses in several animal models of disease. Here, we review the advances and controversy for a role of leptin in the pathophysiology of immune responses and discuss novel possible therapeutic implications for leptin modulators. PMID- 22040698 TI - Immunity as a link between obesity and insulin resistance. AB - Obesity is a major public health problem in the United States and worldwide. Further, obesity is causally linked to the pathogenesis of insulin resistance, metabolic syndrome and type-2 diabetes (T2D). A chronic low-grade inflammation occurring in adipose tissue is at least in part responsible for the obesity induced insulin resistance. This adipose tissue inflammation is characterized by changes in immune cell populations giving rise to altered adipo/cytokine profiles, which in turn induces skeletal muscle and hepatic insulin resistance. Detailed molecular mechanisms of insulin resistance, adipose tissue inflammation and the implications of these findings on therapeutic strategies are discussed in this review. PMID- 22040699 TI - Acute heart failure syndromes: initial management. AB - Postdischarge mortality and morbidity from acute heart failure syndrome (AHFS) are high, affecting nearly half of all discharged patients within 90 days. Emergency department therapy remains largely empiric, with minimal evidence to support definitive recommendations to guide therapy. However, lessons learned from recent registries and trials suggest an approach to initial management based on clinical profiles, as defined by high, normal, or low blood pressure. Clinicians are provided with a practical and consensus-driven approach to everyday AHFS management. PMID- 22040700 TI - Acute coronary syndrome clinical presentations and diagnostic approaches in the emergency department. AB - This article discusses clinical presentations and diagnostic approaches to acute coronary syndrome in the emergency department. PMID- 22040701 TI - Emergency department treatment of acute coronary syndromes. AB - Acute coronary syndrome (ACS) is a broad term encompassing a spectrum of acute myocardial ischemia and injury ranging from unstable angina and non-ST-segment elevation myocardial infarction to ST-segment elevation myocardial infarction. ACS accounts for approximately 1.2 million hospital admissions in the United States annually. The aging of the United States population, along with the national obesity epidemic and the associated increase in metabolic syndrome, means that the number of individuals at risk for ACS will continue to increase for the foreseeable future. This article reviews the current evidence and guidelines for the treatment of patients along the continuum of ACS. PMID- 22040702 TI - A phased approach to cardiac arrest resuscitation involving ventricular fibrillation and pulseless ventricular tachycardia. AB - With the release of the 2010 American Heart Association (AHA) Guidelines for cardiopulmonary resuscitation and emergency cardiac care, evidence regarding management of out-of-hospital cardiac arrest suggests a more fundamental approach. To aid in understanding and learning, this article proposes a method that optimizes the timing and delivery of evidence-proven therapies with a 3 phase approach for out-of-hospital resuscitation from ventricular fibrillation and pulseless ventricular tachycardia. Although this model is not a new concept, it is largely based on the 2010 AHA Guidelines, enhancing the philosophy of the "CAB" concept (Chest compressions/Airway management/Breathing rescue). PMID- 22040703 TI - Approach to the ED patient with "low-risk" chest pain. AB - Patients who present to the ED with chest pain (or its equivalent) but have no electrocardiographic changes or elevation in cardiac biomarkers after an appropriate interval can be considered low risk for acute coronary syndrome. Combined with a low demographic risk for coronary artery disease (eg, using Framingham criteria), such patients can be said to be "low risk" for a subsequent coronary event. Whether there is a role for further risk stratification with provocative testing and/or coronary imaging before discharge remains open to debate. PMID- 22040704 TI - Rhythm disturbances. AB - Patients with cardiac rhythm disturbances may present in a variety of conditions. Patients may be unstable, requiring immediate interventions, or stable, allowing for a more deliberate approach. Rapid assessment of patient stability, underlying rhythm, and determination of appropriate interventions guides timely therapy. This article discusses the differential diagnosis and treatment of adult patients presenting with primary bradyarrhythmias and tachyarrhythmias, with the exception of atrial fibrillation and atrial flutter, covered elsewhere in this issue. A concise approach to diagnosis and determination of appropriate therapy is presented. PMID- 22040705 TI - Atrial fibrillation. AB - Atrial fibrillation (AF) results from the chaotic depolarization of atrial tissue and is the most common dysrhythmia diagnosed in United States (US) emergency departments. AF affects greater than 1% of the general population, with a peak prevalence of 10% in those greater than 80 years of age. By 2050, it is estimated that nearly 16 million US patients will suffer from AF. AF has significant health effects, and places a considerable economic burden on the health care system. This article discusses recommendations that are derived from a combination of existing guidelines, additional evidence, and consensus. PMID- 22040706 TI - Emergency echocardiography. AB - Emergency echocardiography refers to the use of cardiac ultrasound to address critical and time-sensitive clinical questions during the initial evaluation and treatment of the critically ill patient presenting to the emergency department. The information obtained can be pivotal to a physician's clinical decision making and can guide further diagnostic or therapeutic interventions. This article provides an evidence-based discussion of the common uses of emergency transthoracic echocardiography, as well as its benefits and limitations in the current practice of emergency medicine. PMID- 22040707 TI - Aortic emergencies. AB - Aortic emergencies present a diagnostic and treatment challenge for emergency physicians. Both acute aortic dissection and abdominal aortic aneurysms can be difficult to recognize, and a missed or delayed diagnosis may be fatal. A high clinical suspicion and rapid patient evaluation are important. Although many patients ultimately require surgical intervention, early and aggressive attention to hemodynamic stability by the emergency physician can provide a window to definitive treatment. PMID- 22040708 TI - Diagnosis and management of valvular heart disease in emergency medicine. AB - A popular saying holds that if one can hear a heart murmur in the middle of a loud and busy emergency department, then by definition the murmur is significant. Whether or not this is actually true, it does capture the frustration emergency physicians feel when trying to diagnose or manage valvular pathologic conditions with familiar yet limited tools. This article focuses on the valve-related issues the emergency physician will face, from the trauma patient with a mechanical valve who may need his or her anticoagulation reversed to the febrile patient with a new murmur. PMID- 22040709 TI - Congenital heart disease. AB - Pediatric congenital heart disease comprises a wide spectrum of structural defects. These lesions present in a limited number of ways. An infant presenting with profound shock, cyanosis, or evidence of congestive heart failure should raise the suspicion of congenital heart disease. Although most congenital lesions are diagnosed in utero, the emergency physician must be aware of these cardinal presentations because many patients present in the postnatal period around the time that the ductus arteriosus closes. Aggressive management of cardiopulmonary instability combined with empiric use of prostaglandin E(1) and early pediatric cardiology consultation is essential for positive outcomes. PMID- 22040710 TI - Foreword: cardiovascular emergencies. PMID- 22040711 TI - Preface: cardiovascular emergencies. PMID- 22040712 TI - Environmental assessment of recycled printing and writing paper: a case study in China. AB - A life cycle assessment was conducted using IMPACT2002+ to estimate the environmental impact of producing printing and writing paper, which is entirely made with wastepaper. To confirm and add credibility to the study, uncertainty analysis was conducted using Taylor series expansion. Printing and writing paper produced from wood pulp was assessed for comparison. Compared with the wood pulp contained scenario, printing and writing paper made from wastepaper represented environmental benefit on non-carcinogens, respiratory inorganics, global warming, and non-renewable energy categories. In both scenarios, the technologies significantly contribute to the potential impacts of non-carcinogens, respiratory inorganics, terrestrial ecotoxicity, global warming, and non-renewable energy. The influence of the technologies on the way other categories affect the environment was negligible. Improved efficiency in electricity consumption, decreased transport distance from raw material buyers to suppliers, and change in the end-life treatment of solid waste from landfill to incineration are the key factors in reducing the overall environmental impact. PMID- 22040713 TI - Nitrogen removal assessment through nitrification rates and media biofilm accumulation in an IFAS process demonstration study. AB - An IFAS demonstration study was conducted at the 76,000 m(3)/day (20MGD) James River Wastewater Treatment Plant (JRTP) located in Newport News, Virginia by converting one fully-aerobic conventional aeration basin with dedicated secondary clarification to a 7041 m(3)/day (8404 m(3)/day max month) IFAS train in a modified Ludzack-Ettinger (MLE) configuration. During the study, biomass concentrations on the biofilm carriers were monitored (weekly) as well as nitrogen species concentrations in the IFAS reactor to quantify the nitrogen transformations occurring within the demonstration tank. In a related effort, nitrification kinetics for ammonia and nitrite oxidizing bacteria were monitored on a weekly basis for IFAS media alone, IFAS process mixed liquor without media, and IFAS mixed liquor and media together in an effort to identify the location of nitrification activity (i.e. on the media or in the suspended culture) in the IFAS process. Biomass quantity on the media was generally observed to be inversely related to temperature except during a period when an auxiliary carbon source contaminated with fungi was introduced. Both ammonia oxidizing and nitrite oxidizing bacterial activity were elevated on the carriers compared to the suspended culture (AOB(media): 4.97 mgNOx/gMLSS/hr; AOB(suspended): 1.72 mgNOx/gMLSS/hr; NOB(media): 7.55 mgNOx/gMLSS/hr; NOB(suspended): 0.82 mgNOx/gMLSS/hr) during all periods of the study. In-basin nitrification rates calculated based on nitrogen profiling efforts averaged 0.90 mgNOx/m(2)/day which was in good agreement with the average of 0.89 mgNOx/m(2)/day for IFAS mixed liquor and media from batch testing. PMID- 22040714 TI - Frequency of use controls chemical leaching from drinking-water containers subject to disinfection. AB - Microbial-, and chemical-based burden of disease associated with lack of access to safe water continues to primarily impact developing countries. Cost-effective health risk-mitigating measures, such as of solar disinfection applied to microbial-contaminated water stored in plastic bottles have been increasingly tested in developing countries adversely impacted by epidemic water-borne diseases. Public health concerns associated with chemical leaching from water packaging materials led us to investigate the magnitude and variability of antimony (Sb) and bromine (Br) leaching from reused plastic containers (polyethylene terephthalate, PET; and polycarbonate, PC) subject to UV and/or temperature-driven disinfection. The overall objective of this study was to determine the main and interactive effects of temperature, UV exposure duration, and frequency of bottle reuse on the extent of leaching of Sb and Br from plastic bottles into water. Regardless of UV exposure duration, frequency of reuse (up to 27 times) was the major factor that linearly increased Sb leaching from PET bottles at all temperatures tested (13-47 degrees C). Leached Sb concentrations (~360 ng L(-1)) from the highly reused (27 times) PET bottles (minimal Sb leaching from PC bottles, <15 ng L(-1)) did not pose a serious risk to human health according to current daily Sb acceptable intake estimates. Leached Br concentrations from both PET and PC containers (up to ~15 MUg L(-1)) did not pose a consumer health risk either, however, no acceptable daily dose estimates exist for oral ingestion of organo-brominated, or other plasticizers/additives compounds if they were to be found in bottled water at much lower concentrations. Additional research on potential leaching of organic chemicals from water packaging materials is deemed necessary under relevant environmental conditions. PMID- 22040715 TI - Mortality in patients with hip fracture aged over 90 years: a report from a progressively aging island. AB - INTRODUCTION: In our aging society, hip fractures are common in elderly patients, especially those aged above 90 years. Improving mortality rates after this injury is an important part of medical management for the elderly. This study assessed mortality rates after hip fracture in patients aged >=90 years and examined factors that contribute to mortality. METHOD: Between April 2003 and March 2009, 186 patients aged >=65 years were studied. Of these, 50 patients were aged >=90 years. Walking ability before injury and at discharge, preoperative physical status, number of comorbidities, postoperative survival, sex, fracture type, and patients' residential status were investigated. RESULTS: One-year mortality was higher in patients aged >=90 years (24%) than in younger patients (10%) (p=0.01). Moreover, older patients were less likely to retain walking ability at discharge, and poor postoperative ambulatory levels were associated with increased mortality. Preoperative physical status according to the grading system of the American Society of Anesthesiologists (ASA) did not differ between the two age groups. Poor ASA grade was associated with mortality in the entire population, but this association was not significant in the older group. Although older patients had a higher number of trochanteric fractures, fracture type and mortality did not significantly correlate with age. CONCLUSION: Acceptable outcomes of hip fracture surgery can be achieved in very old patients. In addition, postoperative ambulatory level may be a predictor of mortality. PMID- 22040716 TI - Outcome predictors affecting the efficacy of clonazepam therapy for the management of burning mouth syndrome (BMS). AB - BMS is a common condition characterized by chronic oral mucosal pain condition and primarily affects elderly women. Although clonazepam therapy has been widely used due to its efficacy, it is not always effective because of the complexity of BMS pathogenesis. In this study, we have investigated outcome predictors of clonazepam therapy in patients with BMS. One hundred patients with BMS (7 men and 93 women, mean age 58.5 +/- 10.8 years) were instructed to take 0.5mg of clonazepam once or twice daily for 4 weeks. The patients were sub-grouped according to psychological status, salivary flow rate, presence of psychiatric medications, symptom area and duration, symptom severity, presence of oral parafunctions, and accompanying oral complaints. The changes in symptoms were analyzed and compared between the sub-groups. Subjects with T-scores <=50 for each psychological symptom dimension, a greater degree of initial symptoms (visual analog scale (VAS)>=5), and accompanying oral complaints, such as xerostomia and taste disturbance, displayed greater decreases in symptoms compared with their counterparts. In conclusion, psychological status, initial symptom severity, and the presence of xerostomia and/or taste disturbance can serve as outcome predictors of clonazepam therapy for patients with BMS. PMID- 22040717 TI - A genetic polymorphism in the CAV1 gene associates with the development of bronchiolitis obliterans syndrome after lung transplantation. AB - BACKGROUND: Caveolin 1 (Cav-1) is the primary structural component of cell membrane invaginations called 'caveolae'. Expression of Cav-1 is implicated in the pathogenesis of pulmonary fibrosis. Genetic polymorphisms in the CAV1 gene influence the function of Cav-1 in malignancies and associate with renal allograft fibrosis. Chronic allograft rejection after lung transplantation, called 'bronchiolitis obliterans syndrome' (BOS), is also characterised by the development of fibrosis.In this study, we investigated whether CAV1 genotypes associate with BOS and whether Cav-1 serum levels are influenced by the CAV1 genotype and can be used as a biomarker to predict the development of BOS. METHODS: Twenty lung transplant recipients with BOS (BOSpos), ninety without BOS (BOSneg) and four hundred twenty-two healthy individuals donated DNA samples. Four SNPs in CAV1 were genotyped. Serial Cav-1 serum levels were measured in a matched cohort of 10 BOSpos patients and 10 BOSneg patients. Furthermore, single time point Cav-1 serum levels were measured in 33 unmatched BOSneg patients and 60 healthy controls. RESULTS: Homozygosity of the minor allele of rs3807989 was associated with an increased risk for BOS (odds ratio: 6.13; P = 0.0013). The median Cav-1 serum level was significantly higher in the BOSpos patients than in the matched BOSneg patients (P = 0.026). Longitudinal analysis did not show changes in Cav-1 serum levels over time in both groups. The median Cav-1 serum level in the group of 43 BOSneg patients was lower than that in the healthy control group (P = 0.046).In lung transplant recipients, homozygosity of the minor allele of rs3807989 and rs3807994 was associated with increased Cav-1 serum levels. CONCLUSION: In lung transplant recipients, the CAV1 SNP rs3807989 was associated with the development of BOS and Cav-1 serum levels were influenced by the CAV1 genotype. PMID- 22040718 TI - The editor's roundtable: role of percutaneous coronary intervention and drug eluting stents in patients with stable coronary heart disease. PMID- 22040719 TI - Comparison of ascending aortic size in patients with severe bicuspid aortic valve stenosis treated with versus without a statin drug. AB - Ascending aortic dilation commonly occurs in patients with bicuspid aortic valve (BAV). Statins have been shown to reduce the expression of matrix metalloproteinases and slow the progression of abdominal aortic aneurysms. The role of statins in slowing ascending aortic dilation in patients with BAV is unknown. We sought to compare the ascending aortic dimensions in patients with BAV stenosis treated with versus without a statin. From our catheterization laboratory database, all patients undergoing preoperative coronary angiography before aortic valve with or without ascending aorta replacement for bicuspid aortic stenosis (AS) from 2004 to 2007 were identified. The ascending aortic size was measured on their preoperative transesophageal echocardiogram. Data on statin use were obtained from chart review, and the ascending aortic size was compared between patients taking and not taking a statin. The study sample included 147 patients, of whom 76 were treated with statins (mean age 62 +/- 9 years, 72% men) and 71 were not (mean age 59 +/- 12 years, 68% men). The total and low-density lipoprotein cholesterol and triglyceride levels were significantly lower in the statin group. The ascending aorta size was significantly lower in the statin subgroup of the pure severe AS group (3.6 +/- 0.7 cm vs 3.9 +/- 0.6 cm, p < 0.01) but not in the mixed severe AS and severe aortic regurgitation group. In the pure severe AS group, significantly fewer patients taking a statin had an ascending aorta >= 4 cm (29% vs 52%, p < 0.02). On multivariate analysis, statin use was the only independent predictor of aortic size and was associated with a 0.33-cm reduction in aortic size (95% confidence interval 0.06 to 0.59, p < 0.01). In conclusion, patients with statin-treated BAV stenosis have a smaller ascending aortic size than patients with BAV untreated with statins. PMID- 22040721 TI - Right-dominant unbalanced atrioventricular canal and genetic syndromes. PMID- 22040722 TI - The transfer of iron between ceruloplasmin and transferrins. AB - BACKGROUND: It is over 60years since the discovery and isolation of the serum ferroxidase ceruloplasmin. In that time much basic information about the protein has been elucidated including its catalytic and kinetic properties as an enzyme, expression, sequence and structure. The importance of its biological role is indicated in genetic diseases such as aceruloplasminemia where its function is lost through mutation. Despite this wealth of data, fundamental questions about its action remain unanswered and in this article we address the question of how ferric iron produced by the ferroxidase activity of ceruloplasmin could be taken up by transferrins or lactoferrins. METHODS: Overlapping peptide libraries for human ceruloplasmin have been probed with a number of different lactoferrins to identify putative lactoferrin-binding regions on human ceruloplasmin. Docking software, 3D-Garden, has been used to model the binding of human lactoferrin to human ceruloplasmin. RESULTS: Upon probing the human ceruloplasmin library with human lactoferrin, three predominantly acidic lactoferrin-binding peptides, located in domains 2, 5 and 6 of human ceruloplasmin, were identified. The docking software identified a complex such that the N-lobe of human apo lactoferrin interacts with the catalytic ferroxidase centre on human ceruloplasmin. GENERAL SIGNIFICANCE: In vitro binding studies and molecular modelling indicate that lactoferrin can bind to ceruloplasmin such that a direct transfer of ferric iron between the two proteins is possible. A direct transfer of ferric iron from ceruloplasmin to lactoferrin would prevent both the formation of potentially toxic hydroxyl radicals and the utilization of iron by pathogenic bacteria. PMID- 22040723 TI - Fundamental properties of Ca2+ signals. AB - BACKGROUND: Ca2+ is a ubiquitous and versatile second messenger that transmits information through changes of the cytosolic Ca2+ concentration. Recent investigations changed basic ideas on the dynamic character of Ca2+ signals and challenge traditional ideas on information transmission. SCOPE OF REVIEW: We present recent findings on key characteristics of the cytosolic Ca2+ dynamics and theoretical concepts that explain the wide range of experimentally observed Ca2+ signals. Further, we relate properties of the dynamical regulation of the cytosolic Ca2+ concentration to ideas about information transmission by stochastic signals. MAJOR CONCLUSIONS: We demonstrate the importance of the hierarchal arrangement of Ca2+ release sites on the emergence of cellular Ca2+ spikes. Stochastic Ca2+ signals are functionally robust and adaptive to changing environmental conditions. Fluctuations of interspike intervals (ISIs) and the moment relation derived from ISI distributions contain information on the channel cluster open probability and on pathway properties. GENERAL SIGNIFICANCE: Robust and reliable signal transduction pathways that entail Ca2+ dynamics are essential for eukaryotic organisms. Moreover, we expect that the design of a stochastic mechanism which provides robustness and adaptivity will be found also in other biological systems. Ca2+ dynamics demonstrate that the fluctuations of cellular signals contain information on molecular behavior. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling. PMID- 22040724 TI - Potentiation of C1-esterase inhibitor by heparin and interactions with C1s protease as assessed by surface plasmon resonance. AB - BACKGROUND: Human C1-esterase inhibitor (C1-INH) is a multifunctional plasma protein with a wide range of inhibitory and non-inhibitory properties, mainly recognized as a key down-regulator of the complement and contact cascades. The potentiation of C1-INH by heparin and other glycosaminoglycans (GAGs) regulates a broad spectrum of C1-INH activities in vivo both in normal and disease states. SCOPE OF RESEARCH: We have studied the potentiation of human C1-INH by heparin using Surface Plasmon Resonance (SPR), circular dichroism (CD) and a functional assay. To advance a SPR for multiple-unit interaction studies of C1-INH we have developed a novel (consecutive double capture) approach exploring different immobilization and layout. MAJOR CONCLUSIONS: Our SPR experiments conducted in three different design versions showed marked acceleration in C1-INH interactions with complement protease C1s as a result of potentiation of C1-INH by heparin (from 5- to 11-fold increase of the association rate). Far-UV CD studies suggested that heparin binding did not alter C1-INH secondary structure. Functional assay using chromogenic substrate confirmed that heparin does not affect the amidolytic activity of C1s, but does accelerate its consumption due to C1-INH potentiation. GENERAL SIGNIFICANCE: This is the first report that directly demonstrates a significant acceleration of the C1-INH interactions with C1s due to heparin by using a consecutive double capture SPR approach. The results of this study may be useful for further C-INH therapeutic development, ultimately for the enhancement of current C1-INH replacement therapies. PMID- 22040725 TI - A case of Powassan viral hemorrhagic encephalitis involving bilateral thalami. PMID- 22040726 TI - Glioblastoma multiforme of the conus medullaris in a 28-year-old female: a case report and review of the literature. PMID- 22040727 TI - Shunt overdrainage after mild head trauma. PMID- 22040728 TI - Glutamate input to noradrenergic neurons plays an essential role in the development of morphine dependence and psychomotor sensitization. AB - The brain's noradrenergic system is involved in the development of behaviours induced by drugs of abuse, e.g. dependence and withdrawal, and also reward or psychomotor effects. To investigate how noradrenergic system activity is controlled in the context associated with drug-induced behaviours, we generated a Cre/loxP mouse model in which the essential glutamate NMDA receptor subunit NR1 is ablated in cells expressing dopamine beta-hydroxylase (Dbh). As a result, the noradrenergic cells in NR1DbhCre mice lack the NMDA receptor-dependent component of excitatory post-synaptic currents. The mutant mice displayed no obvious behavioural alterations, had unchanged noradrenaline content and mild increase in dopamine levels in the nucleus accumbens. Interestingly, NR1DbhCre animals did not develop morphine-induced psychomotor sensitization. However, when the morphine injections were preceded by treatment with RX821002, an antagonist of alpha2-adrenergic receptors, the development of sensitization was restored. Conversely, pretreatment with clonidine, an agonist of alpha2-adrenergic receptors, blocked development of sensitization in wild-type mice. We also found that while the development of tolerance to morphine was normal in mutant mice, withdrawal symptoms were attenuated. These data reveal that NMDA receptors on noradrenergic neurons regulate development of opiate dependence and psychomotor sensitization, by controlling drug-induced noradrenaline signalling. PMID- 22040729 TI - Simultaneous determination of flucloxacillin and ampicillin in human plasma by ultra performance liquid chromatography-tandem mass spectrometry and subsequent application to a clinical study in healthy Chinese volunteers. AB - A novel method has been developed for the simultaneous determination of flucloxacillin and ampicillin in human plasma by ultra performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS). The plasma was treated by single step of protein precipitation (PPT) with acetonitrile. The chromatographic separation was performed with a mobile phase consisting of 10mM ammonium formate and acetonitrile (68:32, v/v). The analyses were carried out by multiple reaction monitoring (MRM) using the precursor-to-product combinations of m/z 454.1->160.3 (flucloxacillin), m/z 350.1->106.4 (ampicillin) and m/z 436.1 >277.3 (IS). Validation results indicated that the lower limit of quantification (LLOQ) were both 0.2 MUg/mL and both assay exhibited a linear range of 0.2-500 MUg/mL. The intra-batch precision (R.S.D.) was less than 10.6% and inter-batch R.S.D. was less than 11.2%, while accuracy was with +/-8% and +/-9.9%, determined from QC samples for flucloxacillin and ampicillin. A rapid, sensitive and specific method for simultaneous quantifying flucloxacillin and ampicillin in human plasma have been devised and successfully applied to a clinic pharmacokinetic study. PMID- 22040730 TI - Imbalanced pro- and anti-Th17 responses (IL-17/granulocyte colony-stimulating factor) predict fatal outcome in 2009 pandemic influenza. PMID- 22040731 TI - Biochemical and structural analysis of Gox2181, a new member of the SDR superfamily from Gluconobacter oxydans. AB - Gluconobacter oxydans enable to oxidize sugars and polyols incompletely to corresponding materials with potential industrial applications, containing around 75 putative dehydrogenases. One of these putative dehydrogenases, Gox2181, was cloned and expressed in Escherichia coli BL21 (DE3), and its X-ray crystal structure was determined to a resolution of 1.8 A. Gox2181 formed a homo-tetramer in the crystal that was coincident with the apparent molecular mass determined in the solution. Gox2181 displayed alpha/beta-folding patterns, the conserved catalytic tetrad of Asn119-Ser147-Tyr162-Lys166, and the NAD-binding pocket, which aligned well with the 'classical' type of short-chain dehydrogenase/reductase (SDR) enzymes. Gox2181 was denoted SDR51C based on the SDR nomenclature system. The purified recombinant Gox2181 was demonstrated to be NAD(H)-dependent and active towards a wide range of substrates, including sugar alcohols, secondary alcohols, ketones, and ketoses. Among the substrates tested, Gox2181 displayed preference for secondary hydroxyl or carbonyl groups, showing low K(m) values with d-arabitol and butanedione. PMID- 22040732 TI - The signal-anchor sequence of CYP2C1 inserts into the membrane as a hairpin structure. AB - Microsomal cytochrome P450s (CYPs) are anchored to the endoplasmic reticulum membrane by the N-terminal signal-anchor sequence which is predicted to insert into the membrane as a type 1 transmembrane helix with a luminally located N terminus. We have mapped amino acids of the CYP2C1 signal-anchor, fused to Cys free glutathione S-transferase, within the membrane by Cys-specific labeling with membrane-impermeant maleimide polyethylene glycol. At the C-terminal end of the signal-anchor, Trp-20 was mapped to the membrane-cytosol interface and Leu-19 was within the membrane. Unexpectedly, at the N-terminal end, Glu-2 and Pro-3 were mapped to the cytoplasmic side of the membrane rather than the luminal side as expected of a type 1 transmembrane helix. Similar results were observed for the N terminal amino acids of the signal-anchor sequences of CYP3A4 and CYP2E1. These observations indicate that contrary to the current model of the signal-anchor of CYPs as a type 1 transmembrane helix, CYP2C1, CYP2E1, and CYP3A4 are monotopic membrane proteins with N-terminal signal-anchors that have a hairpin or wedge orientation in the membrane. PMID- 22040733 TI - Identification of a second catalytically active trans-sialidase in Trypanosoma brucei. AB - The procyclic stage of Trypanosoma brucei is covered by glycosylphosphatidylinositol (GPI)-anchored surface proteins called procyclins. The procyclin GPI anchor contains a side chain of N-acetyllactosamine repeats terminated by sialic acids. Sialic acid modification is mediated by trans sialidases expressed on the parasite's cell surface. Previous studies suggested the presence of more than one active trans-sialidases, but only one has so far been reported. Here we cloned and examined enzyme activities of four additional trans-sialidase homologs, and show that one of them, Tb927.8.7350, encodes another active trans-sialidase, designated as TbSA C2. In an in vitro assay, TbSA C2 utilized alpha2-3 sialyllactose as a donor, and produced an alpha2-3 sialylated product, suggesting that it is an alpha2-3 trans-sialidase. We suggest that TbSA C2 plays a role in the sialic acid modification of the trypanosome cell surface. PMID- 22040734 TI - Is decreased bone mineral density associated with development of scoliosis? A bipedal osteopenic rat model. AB - BACKGROUND: An association between adolescent idiopathic scoliosis and osteopenia has been proposed to exist. It is still not clear whether there is such an association and if so, whether osteopenia is a causative factor or a consequence. Our previous pilot studies have suggested the presence of osteopenia in scoliotic animals. The aim of this study was to investigate the development of scoliosis in an unpinealectomized bipedal osteopenic rat model, implementing osteoporosis as a causative factor. METHODS: Fifty Sprague-Dawley rats were rendered bipedal at the 3rd postnatal week and separated into control (25 rats) and heparin (25 rats receiving 1 IU/gr body weight/day) groups. DEXA scans after 4 weeks of heparin administration showed low bone mass in the heparin group. Anteroposterior and lateral x-rays of the surviving 42 animals (19 in heparin and 23 in control groups) were taken under anesthesia at the 40th week to evaluate for spinal deformity. Additional histomorphometric analysis was done on spine specimens to confirm the low bone mass in heparin receiving animals. Results of the DEXA scans, histomorphometric analysis and radiological data were compared between the groups. RESULTS: Bone mineral densities of rats in the heparin group were significantly lower than the control group as evidenced by both the DEXA scans and histomorphometric analyses. However, the incidence of scoliosis (82% in heparin and 65% in control; p > 0.05) as well as the curve magnitudes (12.1 +/- 3.8 in heparin versus 10.1 +/- 4.3 degrees in control; p > 0.05) were not significantly different. Osteopenic rats were significantly less kyphotic compared to control specimens (p = 0.001). CONCLUSIONS: This study has revealed two important findings. One is that bipedality (in the absence of pinealectomy) by itself may be a cause of scoliosis in this animal model. Further studies on animal models need to consider bipedality as an independent factor. Secondly, relative hypokyphosis in osteopenic animals may have important implications. The absence of sagittal plane analyses in previous studies makes comparison impossible, but nonetheless these findings suggest that osteopenia may be important in the development of 3D deformity in adolescent idiopathic scoliosis. PMID- 22040735 TI - Retinotopic maps and hemodynamic delays in the human visual cortex measured using arterial spin labeling. AB - Cortical representations of the visual field are organized retinotopically, such that nearby neurons have receptive fields at nearby locations in the image. Many studies have used blood oxygenation level-dependent (BOLD) fMRI to non-invasively construct retinotopic maps in humans. The accuracy of the maps depends on the spatial extent of the metabolic and hemodynamic changes induced by the neural activity. Several studies using gradient-echo MRI at 1.5 T and 3T showed that most of the BOLD signal originates from veins, which might lead to a spatial displacement from the actual site of neuronal activation, thus reducing the specificity of the functional localization. In contrast to BOLD signal, cerebral blood flow (CBF) as measured using arterial spin labeling (ASL) is less or not at all affected by remote draining veins, and therefore spatially and temporally more closely linked to the underlying neural activity. In the present study, we determined retinotopic maps in the human brain using CBF as well as using BOLD signal in order to compare their spatial relationship and the temporal delays of each imaging modality for visual areas V1, V2, V3, hV4 and V3AB. We tested the robustness and reproducibility of the maps across different sessions, calculated the overlap as well as signal delay times across visual areas. While area boundaries were relatively well preserved, we found systematic differences of response latencies between CBF and the BOLD signal between areas. In summary, CBF data obtained using ASL allows reliable retinotopic maps to be constructed; this approach is, therefore, suitable for studying visual areas especially in close proximity to large veins where the BOLD signal is spatially inaccurate. PMID- 22040736 TI - Diffuse and spatially variable white matter disruptions are associated with blast related mild traumatic brain injury. AB - Mild traumatic brain injury (mTBI) due to explosive blast is common among military service members and often associated with long term psychological and cognitive disruptions. Little is known about the neurological effects of blast related mTBI and whether they differ from those of civilian, non-blast mTBI. Given that brain damage from blasts may be diffuse and heterogeneous, we tested the hypothesis that blast mTBI is associated with subtle white matter disruptions in the brain that are spatially inconsistent across individuals. We used diffusion tensor imaging to examine white matter integrity, as quantified by fractional anisotropy (FA), in a group of American military service members with (n=25) or without (n=33) blast-related mTBI who had been deployed as part of Operation Iraqi Freedom or Operation Enduring Freedom. History of civilian non blast mTBI was equally common across groups, which enabled testing of both blast and non-blast mTBI effects on measures sensitive to (1) concentrated, spatially consistent (average FA within a region of interest [ROI]), (2) concentrated, spatially variable (number of ROIs with low average FA), and (3) diffuse (number of voxels with low FA) disruptions of white matter integrity. Blast mTBI was associated with a diffuse, global pattern of lower white matter integrity, and this pattern was not affected by previous civilian mTBI. Neither type of mTBI had an effect on the measures sensitive to more concentrated and spatially consistent white matter disruptions. Additionally, individuals with more than one blast mTBI tended to have a larger number of low FA voxels than individuals with a single blast injury. These results indicate that blast mTBI is associated with disrupted integrity of several white matter tracts, and that these disruptions are diluted by averaging across the large number of voxels within an ROI. The reported pattern of effects supports the conclusion that the neurological effects of blast mTBI are diffuse, widespread, and spatially variable. PMID- 22040737 TI - Response selection versus feedback analysis in conditional visuo-motor learning. AB - Conditional associative sensori-motor learning (i.e. the acquisition of specific arbitrary sensori-motor mappings) involves several processes that depend upon the integrity of the fronto-striatal system. The specific role of the different components of the fronto-striatal system in this type of learning is still unclear and was examined in the present functional Magnetic Resonance Imaging (fMRI) study in humans. The subjects had to learn by trial and error arbitrary associations between visual stimuli and motor responses in an experimental paradigm designed to dissociate between the neuronal substrates specifically involved in the selection of the appropriate response and in the analysis of the feedback obtained during the learning and post-learning periods. First, the results demonstrate that the dorsal premotor (PMd) cortex is the critical structure for the acquisition and execution of arbitrary mappings of visual stimuli to motor responses. Second, they reveal an important shift in activation from the cognitive fronto-striatal network (involving the caudate nucleus, the dorsolateral prefrontal cortex, and the PMd) to the motor fronto-striatal network (involving the putamen and the PMd) as we move from initial learning of sensori motor relations to the post-learning selection of the responses. Finally, they show that feedback processing, but not response selection, increased activity in the anterior cingulate and orbitofrontal cortical regions, demonstrating the selective involvement of these limbic frontal regions in the processing of the consequences of a given action. Altogether our data suggest that, in conditional visuo-motor learning, the associations are critically regulated by the dorsal premotor cortex and the striatum, with additional brain areas contributing to specific aspects of the learning and performance of such associations. PMID- 22040738 TI - Disentangling visual imagery and perception of real-world objects. AB - During mental imagery, visual representations can be evoked in the absence of "bottom-up" sensory input. Prior studies have reported similar neural substrates for imagery and perception, but studies of brain-damaged patients have revealed a double dissociation with some patients showing preserved imagery in spite of impaired perception and others vice versa. Here, we used fMRI and multi-voxel pattern analysis to investigate the specificity, distribution, and similarity of information for individual seen and imagined objects to try and resolve this apparent contradiction. In an event-related design, participants either viewed or imagined individual named object images on which they had been trained prior to the scan. We found that the identity of both seen and imagined objects could be decoded from the pattern of activity throughout the ventral visual processing stream. Further, there was enough correspondence between imagery and perception to allow discrimination of individual imagined objects based on the response during perception. However, the distribution of object information across visual areas was strikingly different during imagery and perception. While there was an obvious posterior-anterior gradient along the ventral visual stream for seen objects, there was an opposite gradient for imagined objects. Moreover, the structure of representations (i.e. the pattern of similarity between responses to all objects) was more similar during imagery than perception in all regions along the visual stream. These results suggest that while imagery and perception have similar neural substrates, they involve different network dynamics, resolving the tension between previous imaging and neuropsychological studies. PMID- 22040740 TI - Characterization of the immunoglobulin repertoire of the spiny dogfish (Squalus acanthias). AB - The cartilaginous fish (chimeras, sharks, skates and rays) are the oldest group relative to mammals in which an adaptive immune system founded upon immunoglobulins has been found. In this manuscript we characterize the immunoglobulins of the spiny dogfish (Squalus acanthias) at both the molecular and expressed protein levels. Despite the presence of hundreds of IgM clusters in this species the serum levels of this isotype are comparatively low. However, analysis of cDNA sequences and serum protein suggests microheterogeneity in the IgM heavy chains and supports the proposal that different clusters are preferentially used in the two forms (monomer or pentamer) of this isotype. We also found that the IgNAR isotype in this species exists in a previously unknown multimeric format in serum. Finally, we identified a new form of the IgW isotype (the shark IgD orthologue), in which the leader is spliced directly to the first constant domain, resulting in a molecule lacking an antigen-binding domain. PMID- 22040739 TI - Ongoing physiological processes in the cerebral cortex. AB - Functional magnetic resonance imaging (fMRI) has revealed that the human brain undergoes prominent, regional hemodynamic fluctuations when a subject is at rest. These ongoing fluctuations exhibit distinct patterns of spatiotemporal synchronization that have been dubbed "resting state functional connectivity", and which currently serve as a principal tool to investigate neural networks in the normal and pathological human brain. Despite the wide application of this approach in human neuroscience, the neural mechanisms that give rise to spontaneous fMRI correlations are largely unknown. Here we review results of recent electrophysiological studies in the cerebral cortex of humans and nonhuman primates that link neural activity to ongoing fMRI fluctuations. We begin by describing results obtained with simultaneous fMRI and electrophysiological measurements that allow for the identification of direct neural correlates of resting state functional connectivity. We next highlight experiments that investigate the correlational structure of spontaneous neural signals, including the spatial variation of signal coherence over the cortical surface, across cortical laminae, and between the two hemispheres. In the final section we speculate on the origins and potential consequences of ongoing signals for normal brain function, and point out inherent limitations of the fMRI correlation approach. PMID- 22040741 TI - A proteome reference map and virulence factors analysis of Yersinia pestis 91001. AB - In this report, we carried out the in-depth proteomic analysis of Yersinia pestis strain 91001 under in vitro flea-simulated condition using three technique routes, SDS-PAGE combined with LTQ-FT, two-dimensional liquid chromatography peptide (2D-LC peptide) separation combined with LTQ-FT and intact protein separation followed by 2D-LC peptide separation combined with LTQ-FT. Totally, 1926 proteins (13082 peptides) were identified, covering 46.50% (1926/4142) of the predicted proteome. Transcriptome analysis based on a whole genome DNA microarray of Y. pestis defined 1655 genes with the coincidence of 56.65% to the proteomic results. Through analyzing the identifications of virulence factors involving in the life cycle of Y. pestis, it was found that Hms system and murine toxin, which are virulence factors involved in Y. pestis maintenance in flea, were highly expressed in our analysis. Moreover, some virulence factors also appeared with different extents, such as plasminogen activator, PhoP/PhoQ two component system, type III secretion system, iron acquisition systems (Ybt, Yfe and Yfu) and ferric uptake regulator. These results indicated that Y. pestis may prepare itself with various strategies in advance for its survival when it evades the hosts. The protein identifications can be accessed through PRIDE database (http://www.ebi.ac.uk/pride) with accession number 18578-18605 PMID- 22040742 TI - Plasma membrane proteomes of differentially matured dendritic cells identified by LC-MS/MS combined with iTRAQ labelling. AB - Dendritic cells (DCs) play a pivotal role in polarising Th lymphocyte subsets but it is unclear what molecular events occur when DCs generate Th2-type responses. Here, we analysed plasma membrane-enriched fractions from immature, pro-Th1 and pro-Th2 DCs and used a combination of iTRAQ labelling and LC-MS/MS to quantify changes in the proteomes. Analysis was performed on triplicate biological samples and changes verified by flow cytometry. MHC class II molecules and CD29 were up regulated in pro-Th1 DCs whilst CD18 and CD44 were up-regulated in pro-Th2 DCs. One of the most down-regulated molecules in pro-Th1 DCs was YM-1 whilst the greatest decrease in pro-Th2 DCs was NAP-22. Other molecules up-regulated in pro Th2 DC compared to pro-Th1 DCs included some potentially involved in protein folding during antigen processing (clathrin and Rab-7), whilst other non-membrane proteins such as enzymes/transporters related to cell metabolism (malate dehydrogenase, pyruvate kinase, and ATPase Na(+)/K(+)) were also recorded. This suggests that pro-Th2 DCs are more metabolically active while pro-Th1 DCs have a mature 'end state'. Overall, although several molecules were preferentially expressed on pro-Th2 DCs, our proteomics data support the view of a 'limited maturation' of pro-Th2 DCs compared to pro-Th1 DCs. PMID- 22040743 TI - Absence of Helicobacter pylori in healthy laryngeal mucosa. AB - OBJECTIVES: To evaluate the presence of Helicobacter pylori in healthy laryngeal mucosa. DESIGN: Prospective analysis of Helicobacter pylori colonisation in healthy laryngeal mucosa, using the 13C urea breath test and polymerase chain reaction analysis. SUBJECTS: Twenty randomly chosen men (28-78 years) without laryngeal pathology or gastrointestinal disease were investigated. All subjects were scheduled for elective operative procedures, under general, endotracheal anaesthesia. Cytobrush samples were taken for Helicobacter pylori DNA detection. Nested polymerase chain reaction testing was performed on DNA solutions using two primer pairs from the urease A gene of the Helicobacter pylori genome. The 13C urea breath test was performed on two exhalation samples. RESULTS: Eight (40 per cent) of the subjects were positive for urease on urea breath testing; none were positive for Helicobacter pylori DNA on polymerase chain reaction testing. CONCLUSION: Based on these results, we do not consider Helicobacter pylori to be a normal constituent of healthy laryngeal microflora. PMID- 22040745 TI - Metabotropic glutamate receptors and the control of chronic pain. AB - Over the past two decades metabotropic glutamate (mGlu) receptor ligands have been investigated for their potential therapeutic effects in different disorders of the central nervous system (CNS), including anxiety, depression, schizophrenia, and neurodegenerative diseases. In addition, it has been widely demonstrated that mGlu receptors are able to modulate pain transmission both in inflammatory and neuropathic pain models. A large number of preclinical studies combining the use of selective ligands with the knockout strategy have revealed more details about the role of the different mGlu receptor subtypes in the modulation of pain information. This review will address the role of mGlu receptors in pain sensitivity focusing on different strategies to achieve pain control by targeting specific mGlu receptor subtypes. Specifically, pharmacological interventions aimed at inhibiting group I mGlu receptor-mediated signaling and/or potentiating groups II and III mGlu receptor signaling together with an epigenetic approach leading to an increased expression of mGlu2 receptors will be discussed. PMID- 22040746 TI - The potential application of a poly(3,4-ethylenedioxythiopene) modified platinum DNA biosensor in mutation analysis. AB - In this study, we have fabricated a label free DNA biosensor by modifying the platinum wire with electrochemically synthesized poly(3,4-ethylenedioxythiopene) and poly(p-aminobenzoic acid). A designed single-strand DNA oligo was immobilized with the carboxyl group of poly(p-aminobenzoic acid) and served as the probe, a target DNA was then hybridized with the probe under a proper condition. Differential pulse voltammetry was performed to characterize the hybridization efficiency in the presence of daunorubicin hydrochloride that was able to be intercalated into the hybridized double-strand DNA and possessed the redox activity. Our results revealed a satisfied linear correlation between the peak current of differential pulse voltammetry and the concentration of complementary target DNA. On the other hand, the mismatches between the target- and probe-DNA caused a significant reduction of electrochemical response, in which was correlated with the amount of mismatched base pairs, therefore the current DNA biosensor had potential applications not only in DNA quantification but also in mutation detection for clinical diagnostics and laboratory applications. PMID- 22040744 TI - The more the better? The role of polyploidy in facilitating plant invasions. AB - BACKGROUND: Biological invasions are a major ecological and socio-economic problem in many parts of the world. Despite an explosion of research in recent decades, much remains to be understood about why some species become invasive whereas others do not. Recently, polyploidy (whole genome duplication) has been proposed as an important determinant of invasiveness in plants. Genome duplication has played a major role in plant evolution and can drastically alter a plant's genetic make-up, morphology, physiology and ecology within only one or a few generations. This may allow some polyploids to succeed in strongly fluctuating environments and/or effectively colonize new habitats and, thus, increase their potential to be invasive. SCOPE: We synthesize current knowledge on the importance of polyploidy for the invasion (i.e. spread) of introduced plants. We first aim to elucidate general mechanisms that are involved in the success of polyploid plants and translate this to that of plant invaders. Secondly, we provide an overview of ploidal levels in selected invasive alien plants and explain how ploidy might have contributed to their success. CONCLUSIONS: Polyploidy can be an important factor in species invasion success through a combination of (1) 'pre-adaptation', whereby polyploid lineages are predisposed to conditions in the new range and, therefore, have higher survival rates and fitness in the earliest establishment phase; and (2) the possibility for subsequent adaptation due to a larger genetic diversity that may assist the 'evolution of invasiveness'. Alternatively, polyploidization may play an important role by (3) restoring sexual reproduction following hybridization or, conversely, (4) asexual reproduction in the absence of suitable mates. We, therefore, encourage invasion biologists to incorporate assessments of ploidy in their studies of invasive alien species. PMID- 22040747 TI - Sensing small neurotransmitter-enzyme interaction with nanoporous gated ion sensitive field effect transistors. AB - Ion-sensitive field effect transistors with gates having a high density of nanopores were fabricated and employed to sense the neurotransmitter dopamine with high selectivity and detectability at micromolar range. The nanoporous structure of the gates was produced by applying a relatively simple anodizing process, which yielded a porous alumina layer with pores exhibiting a mean diameter ranging from 20 to 35 nm. Gate-source voltages of the transistors demonstrated a pH-dependence that was linear over a wide range and could be understood as changes in surface charges during protonation and deprotonation. The large surface area provided by the pores allowed the physical immobilization of tyrosinase, which is an enzyme that oxidizes dopamine, on the gates of the transistors, and thus, changes the acid-base behavior on their surfaces. Concentration-dependent dopamine interacting with immobilized tyrosinase showed a linear dependence into a physiological range of interest for dopamine concentration in the changes of gate-source voltages. In comparison with previous approaches, a response time relatively fast for detecting dopamine was obtained. Additionally, selectivity assays for other neurotransmitters that are abundantly found in the brain were examined. These results demonstrate that the nanoporous structure of ion-sensitive field effect transistors can easily be used to immobilize specific enzyme that can readily and selectively detect small neurotransmitter molecule based on its acid-base interaction with the receptor. Therefore, it could serve as a technology platform for molecular studies of neurotransmitter-enzyme binding and drugs screening. PMID- 22040748 TI - A biomimetic olfactory-based biosensor with high efficiency immobilization of molecular detectors. AB - The immobilization efficiency of molecular detectors is of great importance with regard to the performances of biosensors such as the sensitivity, stability, and reproducibility. This paper presents a biomimetic olfactory receptor-based biosensor with better performances by improving the immobilization efficiency of molecular detectors for odorant sensing. A mixed self-assembled monolayers (SAMs) functionalized with specific olfactory receptors (ODR-10) was constructed on the sensitive area of surface acoustic wave (SAW) chip. The immobilization of ODR-10 was characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The responses of this biosensor to various odorants were recorded by monitoring the resonance frequency shifts of SAW, which is correlated to the mass loading on its sensitive area. All the results demonstrate this biosensor can specifically respond to the natural ligand of ODR-10, diacetyl, with high sensitivity and stability. The sensitivity is 4 kHz/ng, which is 2* higher than that of previous work. The detection limit is 1.2*10(-11) mM. The major advances on immobilization efficiency of molecular detectors presented in this work could substantially promote and accelerate the researches and applications of olfactory receptor-based biosensors with different transducers, such as quartz crystal microbalance (QCM), surface plasma resonance (SPR), and field effect transistors (FET). PMID- 22040749 TI - Mediator-less highly sensitive voltammetric detection of glutamate using glutamate dehydrogenase/vertically aligned CNTs grown on silicon substrate. AB - A sensitive glutamate biosensor is prepared based on glutamate dehydrogenase/vertically aligned carbon nanotubes (GLDH, VACNTs). Vertically aligned carbon nanotubes were grown on a silicon substrate by direct current plasma enhanced chemical vapor deposition (DC-PECVD) method. The electrochemical behavior of the synthesized VACNTs was investigated by cyclic voltammetry and electrochemical impedance spectroscopic methods. Glutamate dehydrogenase covalently attached on tip of VACNTs. The electrochemical performance of the electrode for detection of glutamate was investigated by cyclic and differential pulse voltammetry. Differential pulse voltammetric determinations of glutamate are performed in mediator-less condition and also, in the presence of 1 and 5 MUM thionine as electron mediator. The linear calibration curve of the concentration of glutamate versus peak current is investigated in a wide range of 0.1-500 MUM. The mediator-less biosensor has a low detection limit of 57 nM and two linear ranges of 0.1-20 MUM with a sensitivity of 0.976 mA mM(-1) cm(-2) and 20-300 MUM with a sensitivity of 0.182 mA mM(-1) cm(-2). In the presence of 1 MUM thionine as an electron mediator, the prepared biosensor shows a low detection limit of 68 nM and two linear ranges of 0.1-20 with a calibration sensitivity of 1.17 mA mM( 1) cm(-2) and 20-500 MUM with a sensitivity of 0.153 mA mM(-1) cm(-2). The effects of the other biological compounds on the voltammetric behavior of the prepared biosensor and its response stability are investigated. The results are demonstrated that the GLDH/VACNTs electrode even without electron mediator is a suitable basic electrode for detection of glutamate. PMID- 22040750 TI - Two steps forward, one step back. PMID- 22040751 TI - Rotator cuff repair healing influenced by platelet-rich plasma construct augmentation: a novel molecular mechanism. PMID- 22040753 TI - Curious about "put your 'extended' finger on the bleeder". PMID- 22040755 TI - Vitamin D status and musculoskeletal health in adolescent male ballet dancers a pilot study. AB - Adequate vitamin D levels during growth are critical to ensuring optimal bone development. Vitamin D synthesis requires sun exposure; thus, athletes engaged in indoor activities such as ballet dancing may be at relatively high risk of vitamin D insufficiency. The objective of this study was to investigate the prevalence of low vitamin D levels in young male ballet dancers and its impact on musculoskeletal health. Eighteen male ballet dancers, aged 10 to 19 years and training for at least 6 hours per week, were recruited from the Australian Ballet School, Melbourne, Australia. Serum 25(OH)D and intact PTH were measured in winter (July) from a non-fasting blood sample. Pubertal stage was determined using self-assessed Tanner criteria. Body composition and areal bone mineral density (aBMD) at the whole body and lumbar spine were measured using dual-energy x-ray absorptiometry (DXA). Injury history and physical activity levels were assessed by questionnaire. Blood samples were obtained from 16 participants. Serum 25(OH)D levels ranged from 20.8 to 94.3 nmol/L, with a group mean of 50.5 nmol/L. Two participants (12.5%) showed vitamin D deficiency [serum 25(OH)D level < 25 nmol/L], seven dancers (44%) had vitamin D insufficiency (25 to 50 nmol/L), and the remaining seven dancers (44%) had normal levels (> 50 nmol/L). No relationship was found between vitamin D status, PTH levels, body composition, and aBMD. The most commonly reported injuries were muscle tears and back pain. The average number of injuries reported by each dancer was 1.9 +/- 0.4 (range: 0 to 5). There was no difference in the frequency of reported injuries between subjects with vitamin D deficiency or insufficiency (2.1 +/- 0.6 injuries) and those with normal vitamin D levels (1.4 +/- 0.6 injuries). This pilot study showed that more than half of highly-trained young male ballet dancers presented with low levels of vitamin D in winter. Further investigations in larger samples of adolescent athletes are needed to determine if this could negatively impact bone growth and place them at higher risk for musculoskeletal injuries. PMID- 22040756 TI - The impact of mirrors on body image and performance in high and low performing female ballet students. AB - This study assesses the effect of mirrors on body image and performance in high and low performing female collegiate ballet students. Twenty-three females enrolled in a beginning ballet class were taught using mirrors, and a second group of 23 beginning females were taught without mirrors. All participants completed the Cash 69-item Body Self-Relations Questionnaire during the first and last class of a 14-week semester. They were videotaped performing in the studio during the fifth and fourteenth weeks. Two ballet teachers independently viewed the videotapes to evaluate the dancers' rhythmic accuracy, ease and flow of movement, and mastery of steps and alignment, and rated the students' skill level on a 1-5 scale. For analysis purposes, students whose scores averaged three or higher were categorized as "high performers," and those who averaged less than three were "low performers." Two (mirror, non-mirror) by two (high performance, low performance) by two (pre-test, post-test) repeated measures ANOVAs were used to test class differences over the course of the semester. There were significant 3-way interactions for overweight preoccupation (p < 0.01) and body-areas satisfaction (p < 0.05). Low performers increased in overweight preoccupation in the non-mirror class while decreasing in the mirror class. High performers significantly increased in satisfaction for most areas of their body in the non mirror class, while there were smaller increases for both low and high performers in the mirror class. It is concluded that while use of the mirror has some benefits in training, higher performing dancers feel better about their body image when they do not use the mirror. Lower performers who use the mirror worry less about their weight; those who do not use the mirror worry more. The mirror may provide feedback that helps low performing dancers feel more comfortable with their weight. PMID- 22040757 TI - Injuries in a modern dance company effect of comprehensive management on injury incidence and cost. AB - Injury costs strain the finances of many dance companies. The objectives of this study were to analyze the effect of comprehensive management on injury patterns, incidence, and time loss and examine its financial impact on workers compensation premiums in a modern dance company. In this retrospective-prospective cohort study, injury was defined as any physical insult that required financial outlay (workers compensation or self insurance) or caused a dancer to cease dancing beyond the day of injury (time-loss injury). Injury data and insurance premiums were analyzed over an eight-year period. Injuries were compared using a mixed linear model with phase and gender as fixed effects. It was found that comprehensive management resulted in 34% decline in total injury incidence, 66% decrease in workers compensation claims, and 56% decrease in lost days. These outcomes achieved substantial savings in workers compensation premiums. Thus, this study demonstrates the effectiveness of an injury prevention program in reducing injury-related costs and promoting dancers' health and wellness in a modern dance company. PMID- 22040758 TI - Development, validity, and reliability of a ballet-specific aerobic fitness test. AB - The aim of this study was to develop and assess the reliability and validity of a multi-stage, ballet-specific aerobic fitness test to be used in a dance studio setting. The test consists of five stages, each four minutes long, that increase in intensity. It uses classical ballet movement of an intermediate-level of difficulty, thus emphasizing physiological demand rather than skill. The demand of each stage was determined by calculating the mean oxygen uptake during its final minute using a portable gas analyser. After an initial familiarization period, eight female subjects performed the test twice within seven days. The results showed significant differences in oxygen consumption between stages (p < 0.001), but not between trials. Pearson correlation co-efficients produced a very good linear relationship between trials (r = 0.998, p < 0.001). Bland-Altman reliability analysis revealed the 95% limits of agreement to be +/- 6.2 ml.kg( 1).min(-1), showing good agreement between trials. The oxygen uptake in our subjects equated positively to previous estimates for class and performance, confirming validity. It was concluded that the test is suitable for use among classical ballet dancers, with many possible applications. PMID- 22040759 TI - The effect of sprung (suspended) floors on leg stiffness during grand jete landings in ballet. AB - This study compared stiffness of the landing leg in ballet dancers performing grand jete on a sprung floor to leg stiffness during the same movement on a hard floor (wood on concrete). Leg stiffness was calculated as the ratio of vertical ground reaction force (in Newtons) to compression of the lower limb (in meters). Thirteen female dancers were measured for five repetitions each at the point of maximum leg compression while landing grand jete on both of the surfaces, such that 20 milliseconds of data were represented for each trial. The stiffness of the landing leg at the point of maximum compression was decreased by a mean difference score of 6168.0 N/m +/- 11,519.5 N/m on the hard floor compared to the sprung floor. Paired t-test yielded a one-tailed probability of p = 0.038. This effect was seen in 11 of the 13 participants. The finding of increased stiffness of the landing leg in the sprung floor condition suggests that some of the force of landing the leap was absorbed by the surface, and therefore did not need to be absorbed by the landing leg itself. This in turn implies that a sprung dance floor may help to prevent dance-related injuries. PMID- 22040760 TI - Follow-up study to "The effect of sprung (suspended) floors on leg stiffness during grand jete landings in ballet". PMID- 22040761 TI - The use of stabilization exercises and movement reeducation to manage pain and improve function in a dancer with focal degenerative joint disease of the spine. AB - Little has been written about rehabilitation of low back pain (LBP) specific to the professional dancer. However, there is a rapidly increasing amount of rehabilitation research related to the care of LBP in the general population that may be applied to the dancer population. The purpose of this case report is to describe the physical therapy management of a 37-year-old female professional dancer with a 5-year history of spinal pain and loss of function in the presence of degenerative joint disease at a single segment (T12-L1). Patient interventions focused on stabilization exercises and movement reeducation. The dancer returned to limited dance performance at 6 weeks. At 5 months she had returned to complete dance function, with pain and functional (Oswestry) levels improved from initial values of 7/10 and 48%, respectively, to 1/10 and 26%. PMID- 22040763 TI - Phylogeny and historical biogeography of ancient assassin spiders (Araneae: Archaeidae) in the Australian mesic zone: evidence for Miocene speciation within Tertiary refugia. AB - The rainforests, wet sclerophyll forests and temperate heathlands of the Australian mesic zone are home to a diverse and highly endemic biota, including numerous old endemic lineages restricted to refugial, mesic biomes. A growing number of phylogeographic studies have attempted to explain the origins and diversification of the Australian mesic zone biota, in order to test and better understand the mode and tempo of historical speciation within Australia. Assassin spiders (family Archaeidae) are a lineage of iconic araneomorph spiders, characterised by their antiquity, remarkable morphology and relictual biogeography on the southern continents. The Australian assassin spider fauna is characterised by a high diversity of allopatric species, many of which are restricted to individual mountains or montane systems, and all of which are closely tied to mesic and/or refugial habitats in the east and extreme south-west of mainland Australia. We tested the phylogeny and vicariant biogeography of the Australian Archaeidae (genus Austrarchaea Forster & Platnick), using a multi locus molecular approach. Fragments from six mitochondrial genes (COI, COII, tRNA K, tRNA-D, ATP8, ATP6) and one nuclear protein-coding gene (Histone H3) were used to infer phylogenetic relationships and to explore the phylogeographic origins of the diverse Australian fauna. Bayesian analyses of the complete molecular dataset, along with differentially-partitioned Bayesian and parsimony analyses of a smaller concatenated dataset, revealed the presence of three major Australian lineages, each with non-overlapping distributions in north-eastern Queensland, mid-eastern Australia and southern Australia, respectively. Divergence date estimation using mitochondrial data and a rate-calibrated relaxed molecular clock revealed that major lineages diverged in the early Tertiary period, prior to the final rifting of Australia from East Antarctica. Subsequent speciation occurred during the Miocene (23-5.3 million years ago), with tropical and subtropical taxa diverging in the early-mid Miocene, prior to southern and temperate taxa in the mid-late Miocene. Area cladograms reconciled with Bayesian chronograms for all known Archaeidae in southern and south-eastern Australia revealed seven potentially vicariant biogeographic barriers in eastern Queensland, New South Wales and southern Australia, each proposed and discussed in relation to other mesic zone taxa. Five of these barriers were inferred as being of early Miocene age, and implicated in the initial vicariant separation of endemic regional clades. Phylogeographic results for Australian Archaeidae are congruent with a model of sequential allopatric speciation in Tertiary refugia, as driven by the contraction and fragmentation of Australia's mesic biomes during the Miocene. Assassin spiders clearly offer great potential for further testing historical biogeographic processes in temperate and eastern Australia, and are a useful group for better understanding the biology and biogeography of the Australian mesic zone. PMID- 22040762 TI - Bilateral kidney preservation by volumetric-modulated arc therapy (RapidArc) compared to conventional radiation therapy (3D-CRT) in pancreatic and bile duct malignancies. AB - BACKGROUND: To compare volumetric-modulated arc therapy plans with conventional radiation therapy (3D-CRT) plans in pancreatic and bile duct cancers, especially for bilateral kidney preservation. METHODS: A dosimetric analysis was performed in 21 patients who had undergone radiotherapy for pancreatic or bile duct carcinoma at our institution. We compared 4-field 3D-CRT and 2 arcs RapidArc (RA) plans. The treatment plan was designed to deliver a dose of 50.4 Gy to the planning target volume (PTV) based on the gross disease in a 1.8 Gy daily fraction, 5 days a week. Planning objectives were 95% of the PTV receiving 95% of the prescribed dose and no more than 2% of the PTV receiving more than 107%. Dose volume histograms (DVH) for the target volume and the organs at risk (right and left kidneys, bowel tract, liver and healthy tissue) were compared. Monitor units and delivery treatment time were also reported. RESULTS: All plans achieved objectives, with 95% of the PTV receiving >= 95% of the dose (D95% for 3D-CRT = 48.9 Gy and for RA = 48.6 Gy). RapidArc was shown to be superior to 3D-CRT in terms of organ at risk sparing except for contralateral kidney: for bowel tract, the mean dose was reduced by RA compared to 3D-CRT (16.7 vs 20.8 Gy, p = 0.0001). Similar result was observed for homolateral kidney (mean dose of 4.7 Gy for RA vs 12.6 Gy for 3D-CRT, p < 0.0001), but 3D-CRT significantly reduced controlateral kidney dose with a mean dose of 1.8 Gy vs 3.9 Gy, p < 0.0007. Compared to 3D-CRT, mean MUs for each fraction was significantly increased with RapidArc: 207 vs 589, (p < 0.0001) but the treatment time was not significantly different (2 and 2.66 minutes, p = ns). CONCLUSION: RapidArc allows significant dose reduction, in particular for homolateral kidney and bowel, while maintaining target coverage. This would have a promising impact on reducing toxicities. PMID- 22040764 TI - Codon usage patterns and adaptive evolution of marine unicellular cyanobacteria Synechococcus and Prochlorococcus. AB - Marine unicellular cyanobacteria, represented by Synechococcus and Prochlorococcus, dominate the total phytoplankton biomass and production in oligotrophic ocean. In this study, we employed comparative genomics approaches to extensively investigate synonymous codon usage bias and evolutionary rates in a large number of closely related species of marine unicellular cyanobacteria. Although these two groups of marine cyanobacteria have a close phylogenetic relationship, we find that they are highly divergent not only in codon usage patterns but also in the driving forces behind the diversification. It is revealed that in Prochlorococcus, mutation and genome compositional constraints are the main forces contributing to codon usage bias, whereas in Synechococcus, translational selection. In addition, nucleotide substitution rate analysis indicates that they are not evolving at a constant rate after the divergence and that the average d(N)/d(S) values of core genes in Synechococcus are significantly higher than those in Prochlorococcus. Our evolutionary genomic analysis provides the first insight into codon usage, evolutionary genetic mechanisms and environmental adaptation of Synechococcus and Prochlorococcus after divergence. PMID- 22040765 TI - Estimation of divergence times in cnidarian evolution based on mitochondrial protein-coding genes and the fossil record. AB - The phylum Cnidaria is comprised of remarkably diverse and ecologically significant taxa, such as the reef-forming corals, and occupies a basal position in metazoan evolution. The origin of this phylum and the most recent common ancestors (MRCAs) of its modern classes remain mostly unknown, although scattered fossil evidence provides some insights on this topic. Here, we investigate the molecular divergence times of the major taxonomic groups of Cnidaria (27 Hexacorallia, 16 Octocorallia, and 5 Medusozoa) on the basis of mitochondrial DNA sequences of 13 protein-coding genes. For this analysis, the complete mitochondrial genomes of seven octocoral and two scyphozoan species were newly sequenced and combined with all available mitogenomic data from GenBank. Five reliable fossil dates were used to calibrate the Bayesian estimates of divergence times. The molecular evidence suggests that cnidarians originated 741 million years ago (Ma) (95% credible region of 686-819), and the major taxa diversified prior to the Cambrian (543 Ma). The Octocorallia and Scleractinia may have originated from radiations of survivors of the Permian-Triassic mass extinction, which matches their fossil record well. PMID- 22040766 TI - Evolution of arid zone birds in Australia: leapfrog distribution patterns and mesic-arid connections in quail-thrush (Cinclosoma, Cinclosomatidae). AB - The quail-thrush, Cinclosoma, include between five and seven species distributed broadly across arid and semi-arid inland Australia, mesic forests of south eastern Australia and New Guinea. It has been suggested that the arid zone species of quail-thrush arose from forest ancestors as Australia changed from a warm wet climate to a cooler drier climate since the late-Miocene. We generated multilocus (mitochondrial ND2 and eight nuclear loci) gene and species trees with complete taxon sampling of Cinclosoma to investigate evolutionary relationships and species status of some taxa. Topologies reconstructed in congruent, highly resolved gene trees and species trees that supported the recognition of seven species. Ancestral state reconstruction and divergence time estimates suggest that arid-adapted taxa radiated in parallel with a drying climate and changing habitat. A 'leapfrog' distribution in phenotypes of arid zone taxa was likely a result of ancestral retention of inconspicuous (or camouflaged) plumage patterns. A specimen-based report from 1968 of hybridization between non-sister taxa Cinclosoma castanotum and Cinclosoma marginatum was verified using molecular analysis on specimens collected at the same locality 40 years later. We discuss the implications of hybridization to the evolution of this species group. PMID- 22040768 TI - Simultaneous occurrence of a thyroglossal duct cyst and a lingual thyroid in the absence of an orthotopic thyroid gland. AB - OBJECTIVE: We report an extremely rare case of the simultaneous occurrence of a thyroglossal duct cyst and a lingual thyroid in the absence of an orthotopic thyroid gland, in a seven-year-old girl from South India. METHOD: Case report and a review of the English language literature on the subject. RESULTS: The patient presented with a mass on the tongue that had been present for three years, and an anterior neck swelling that had been present for two years. Examination revealed a midline, pinkish, firm mass present on the posterior one-third of the tongue. The neck showed a midline cystic swelling in the infrahyoid position. Radiological imaging confirmed the clinical findings, revealing the absence of her thyroid gland in the normal location. Sistrunk's procedure was performed leaving behind a lingual thyroid. At 13-month follow up, the patient was euthyroid with no recurrence. CONCLUSION: To our knowledge the association of a lingual thyroid and a thyroglossal cyst has only been reported once in the literature. The presence of a lingual thyroid in the absence of a normally located thyroid gland or functioning thyroid tissue along the thyroglossal tract, confirmed by radionuclide and computed tomography imaging, may indicate the failure of the normal descent of the thyroid gland during embryonic development. This probable absence of the descent of the thyroid raises questions regarding the origin of thyroglossal duct cysts. PMID- 22040767 TI - Reconciling molecules and morphology: molecular systematics and biogeography of Neotropical blennies (Acanthemblemaria). AB - Neotropical reef fish communities are species-poor compared to those of the Indo West Pacific. An exception to that pattern is the blenny clade Chaenopsidae, one of only three rocky and coral reef fish families largely endemic to the Neotropics. Within the chaenopsids, the genus Acanthemblemaria is the most species-rich and is characterized by elaborate spinous processes on the skull. Here we construct a species tree using five nuclear markers and compare the results to those from Bayesian and parsimony phylogenetic analyses of 60 morphological characters. The sequence-based species tree conflicted with the morphological phylogenies for Acanthemblemaria, primarily due to the convergence of a suite of characters describing the distribution of spines on the head. However, we were able to resolve some of these conflicts by performing phylogenetic analyses on suites of characters not associated with head spines. By using the species tree as a guide, we used a quantitative method to identify suites of correlated morphological characters that, together, produce the distinctive skull phenotypes found in these fishes. A time calibrated phylogeny with nearly complete taxon sampling provided divergence time estimates that recovered a mid-Miocene origin for the genus, with a temporally and geographically complex pattern of speciation both before and after the closure of the Isthmus of Panama. Some sister taxa are broadly sympatric, but many occur in allopatry. The ability to infer the geography of speciation in Acanthemblemaria is complicated by extinctions, incomplete knowledge of their present geographic ranges and by wide-spread taxa that likely represent cryptic species complexes. PMID- 22040769 TI - An unusual presentation of a chronic ingested foreign body in an adult. AB - BACKGROUND: Sore throat is a common complaint for patients presenting to the emergency department (ED). Although most are caused by viral and bacterial sources, an ingested foreign body must be considered in the right patient population. Retained foreign bodies occur in both children and adults. In children, the objects are usually non-food items, whereas adults are more likely to have impacted food boluses. Typically, patients present acutely, and chronic foreign bodies are rare, especially in adults. OBJECTIVE: We use an unusual presentation of a retained foreign body in a previously undiagnosed Zenker diverticulum to review ingested foreign bodies and Zenker diverticuli. CASE REPORT: We report the case of an 82-year-old woman who presented to the ED with a chief complaint of 12 h of worsening pharyngitis and odynophagia. She reported she had a capsule endoscopy performed approximately 4 months earlier during which the device had malfunctioned and no images were transmitted from beyond the esophagus. A soft tissue film of the neck showed the endoscopic capsule retained at the level of the clavicles. Esophagogastroduodenoscopy demonstrated a previously undiagnosed Zenker diverticulum containing the endoscope capsule. This was subsequently removed with laryngoscopy. CONCLUSION: Complaints related to sore throat commonly have a simple explanation. Recurrent symptoms and a physical examination inconsistent with common explanations require the differential to be broadened and less common causes considered. PMID- 22040770 TI - Acute surgical abdomen due to phytobezoar-induced ileal obstruction. AB - BACKGROUND: Phytobezoar-induced small bowel obstruction is an uncommon clinical entity accounting for 2-4.8% of all mechanical intestinal obstructions. In addition, presentation with features of acute surgical abdomen is extremely rare, accounting for only 1% of the patients. OBJECTIVES: The aim of this report is to present a very rare case of a phytobezoar-induced small bowel obstruction in a male patient who presented with acute surgical abdomen. A correct preoperative diagnosis was made based on the patient's history and characteristic imaging features on the emergency computed tomography (CT) scan. CASE REPORT: A 55-year old man with previous gastrectomy presented with typical manifestations of acute abdomen. CT scan demonstrated dilatated small bowel loops and an intraluminal ileal mass with a mottled appearance. At exploratory laparotomy, a phytobezoar was found impacted in the terminal ileum and was removed through an enterotomy. CONCLUSIONS: Phytobezoar should be considered in patients with previous gastric outlet surgery who present with bowel obstruction and features of acute surgical abdomen. The presence of a well-defined intraluminal mass with a mottled gas pattern on emergency CT scan is suggestive of an intestinal phytobezoar. PMID- 22040771 TI - Characteristics of frequent geriatric users of an urban emergency department. AB - BACKGROUND: As the population ages, it is projected that older adults will increase emergency department (ED) utilization and contribute to ED crowding. Older patients are at risk of decreased health-related quality of life after an ED visit. Characteristics of older adults that frequently use the ED have not been well studied, and prior studies have shown that lack of access to primary care may influence ED utilization. OBJECTIVE: Determine factors associated with frequent Emergency Department (ED) utilization by older adults. METHODS: Retrospective chart review of all patients >= 65 years of age seen in an urban ED between December 2007 and September 2008. A prospective telephone survey was done of "frequent" (>= 4 ED visits over a 6-month period) geriatric users. "Frequent" and "infrequent" geriatric ED users were compared using chi-squared and t-test. Survey results are univariate descriptive statistics. RESULTS: There were 8520 ED visits of adults >= 65 years of age analyzed, of which 5718 were unique patients. Of these, 268 (5%) were frequent ED users. Frequent geriatric ED users were more likely to be Black or Hispanic and were considered less urgent at triage. Of the 59 surveyed frequent users of the ED, 95% reported having a usual source of care, though only 36% contacted their outpatient provider before a visit to the ED. CONCLUSION: Frequent geriatric users of the ED were considered less urgent at triage, and although most identified themselves as having a primary care provider in the community, many did not contact them before going to the ED. PMID- 22040772 TI - Supraspinal regulation of physical fatigue. AB - Fatigue, defined as difficulty in initiating or sustaining voluntary activities, can be classified as physical or mental, and physical fatigue can be classified as peripheral or central (spinal or supraspinal). It has been reported that during physical fatigue, sensory input from the peripheral system activates an inhibition system to limit motor output from the primary motor cortex (M1) (supraspinal fatigue) while a motivational input activates a facilitation system to increase motor output from M1 in order to overcome supraspinal fatigue. Hence, the motor output from M1 is primarily determined by the balance between the inhibition and facilitation systems. Here, we review data from behavioral, electrophysiological, and neuroimaging experiments related to supraspinal mechanisms that are thought to regulate motor output from M1 during physical fatigue, and we propose a supraspinal model to regulate physical fatigue as well as a hypothetical model of fatigue in human diseases or syndromes. PMID- 22040773 TI - An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression. AB - Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of major depressive disorder (MDD). We used proton magnetic resonance spectroscopy (1H-MRS) to investigate whether prefrontal levels of amino acid neurotransmitters predict antidepressant response to a single intravenous infusion of the N-methyl-D-aspartate (NMDA) antagonist ketamine in MDD patients. Fourteen drug-free patients with MDD were scanned 1-3 d before receiving a single intravenous infusion of ketamine (0.5 mg/kg). We measured gamma aminobutyric acid (GABA), glutamate, and Glx/glutamate ratio (a surrogate marker of glutamine) in the ventromedial prefrontal cortex (VM-PFC) and the dorsomedial/dorsal anterolateral prefrontal cortex (DM/DA-PFC). Correlation analyses were conducted to determine whether pretreatment GABA, glutamate, or Glx/glutamate ratio predicted change in depressive and anxiety symptoms 230 min after ketamine administration. Pretreatment GABA or glutamate did not correlate with improved depressive symptoms in either of the two regions of interest (p>0.1); pretreatment Glx/glutamate ratio in the DM/DA-PFC was negatively correlated with improvement in depressive symptoms [r s(11)=-0.57, p<0.05]. Pretreatment glutamate levels in the VM-PFC were positively correlated with improvement in anxiety symptoms [r s(11)=0.57, p<0.05]. The findings suggest an association between lower Glx/glutamate ratio and greater improvement in response to ketamine treatment. Because glutamine is mainly contained in glia, the decreased Glx/glutamate ratio observed in this study may reflect the reduction in glial cells found in the same regions in post-mortem studies of individuals with MDD, and suggests that the presence of this neuropathological construct may be associated with antidepressant responsiveness to ketamine. PMID- 22040774 TI - The synthetic tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis. AB - INTRODUCTION: Angiopoietin-1 (Angpt1), the natural agonist ligand for the endothelial Tie2 receptor, is a non-redundant endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte endothelium interactions. Here we evaluate the efficacy of a novel polyethylene glycol (PEG)-clustered Tie2 agonist peptide, Vasculotide (VT), to protect against vascular leakage and mortality in a murine model of polymicrobial abdominal sepsis. METHODS: Polymicrobial abdominal sepsis in C57BL6 mice was induced by cecal-ligation-and-puncture (CLP). Mice were treated with different dosages of VT or equal volume of phosphate-buffered saline (PBS). Sham-operated animals served as time-matched controls. RESULTS: Systemic administration of VT induced long lasting Tie2 activation in vivo. VT protected against sepsis-induced endothelial barrier dysfunction, as evidenced by attenuation of vascular leakage and leukocyte transmigration into the peritoneal cavity. Histological analysis revealed that VT treatment ameliorated leukocyte infiltration in kidneys of septic mice, probably due to reduced endothelial adhesion molecule expression. VT driven effects were associated with significantly improved organ function and reduced circulating cytokine levels. The endothelial-specific action of VT was supported by additional in vitro studies showing no effect of VT on either cytokine release from isolated peritoneal macrophages, or migratory capacity of isolated neutrophils. Finally, administration of VT pre-CLP (Hazard Ratio 0.39 [95% Confidence interval 0.19-0.81] P < 0.001) and post-CLP reduced mortality in septic mice (HR 0.22 [95% CI 0.06-0.83] P < 0.05). CONCLUSIONS: We provide proof of principle in support of the efficacious use of PEGylated VT, a drug-like Tie2 receptor agonist, to counteract microvascular endothelial barrier dysfunction and reduce mortality in a clinically relevant murine sepsis model. Further studies are needed to pave the road for clinical application of this therapeutic concept. PMID- 22040775 TI - Comparison of internal dosimetry factors for three classes of adult computational phantoms with emphasis on I-131 in the thyroid. AB - The S values for 11 major target organs for I-131 in the thyroid were compared for three classes of adult computational human phantoms: stylized, voxel and hybrid phantoms. In addition, we compared specific absorbed fractions (SAFs) with the thyroid as a source region over a broader photon energy range than the x- and gamma-rays of I-131. The S and SAF values were calculated for the International Commission on Radiological Protection (ICRP) reference voxel phantoms and the University of Florida (UF) hybrid phantoms by using the Monte Carlo transport method, while the S and SAF values for the Oak Ridge National Laboratory (ORNL) stylized phantoms were obtained from earlier publications. Phantoms in our calculations were for adults of both genders. The 11 target organs and tissues that were selected for the comparison of S values are brain, breast, stomach wall, small intestine wall, colon wall, heart wall, pancreas, salivary glands, thyroid, lungs and active marrow for I-131 and thyroid as a source region. The comparisons showed, in general, an underestimation of S values reported for the stylized phantoms compared to the values based on the ICRP voxel and UF hybrid phantoms and relatively good agreement between the S values obtained for the ICRP and UF phantoms. Substantial differences were observed for some organs between the three types of phantoms. For example, the small intestine wall of ICRP male phantom and heart wall of ICRP female phantom showed up to eightfold and fourfold greater S values, respectively, compared to the reported values for the ORNL phantoms. UF male and female phantoms also showed significant differences compared to the ORNL phantom, 4.0-fold greater for the small intestine wall and 3.3-fold greater for the heart wall. In our method, we directly calculated the S values without using the SAFs as commonly done. Hence, we sought to confirm the differences observed in our S values by comparing the SAFs among the phantoms with the thyroid as a source region for selected target organs--small intestine wall, lungs, pancreas and breast--as well as illustrate differences in energy deposition across the energy range (12 photon energies from 0.01 to 4 MeV). Differences were found in the SAFs between phantoms in a similar manner as the differences observed in S values but with larger differences at lower photon energies. To investigate the differences observed in the S and SAF values, the chord length distributions (CLDs) were computed for the selected source--target pairs and compared across the phantoms. As demonstrated by the CLDs, we found that the differences between phantoms in those factors used in internal dosimetry were governed to a significant degree by inter-organ distances which are a function of organ shape as well as organ location. PMID- 22040776 TI - CPR policies and the patient's best interests. AB - Standard hospital CPR policies in many countries require CPR to be attempted on all patients having a cardiac arrest unless a Not-for-CPR order is in place. It has recently been shown that this approach is legally inappropriate in New Zealand. It appears that this argument may also potentially apply in other common law countries given the role that 'best interests' has in these jurisdictions in providing treatment to patients lacking decision-making capacity. Not-for-CPR orders provide an important and transparent mechanism for making advanced decisions regarding resuscitation. However, advanced planning is not always possible and it is legally inappropriate to require CPR to be performed when it is not in the patient's best interests. Notwithstanding the difficult practical balance that exists at the time of arrest between initiating CPR without delay or interruption for it to be effective for those whom CPR is in their best interests, and recognising as quickly as possible those patients for who CPR is not appropriate, it is argued that policies should be modified to allow clinicians to consider whether CPR is appropriate at time of arrest. Such a change may require ALS training to include a stronger emphasis on early recognition of patients for whom CPR is not in their best interests. PMID- 22040777 TI - Expertise in prehospital endotracheal intubation by emergency medicine physicians Comparing 'proficient performers' and 'experts'. AB - BACKGROUND: Training requirements to perform safe prehospital endotracheal intubation (ETI) are not clearly known. This study aimed to determine differences in ETI performance between 'proficient performers' and 'experts' according to the Dreyfus & Dreyfus framework of expertise. As a model for 'proficient performers' EMS physicians with a clinical background in internal medicine were compared to EMS physicians with a background in anaesthesiology as a model for 'experts'. METHODS: Over a one-year period all ETIs performed by the EMS physicians of our institution were prospectively evaluated. 'Proficient performers' and 'experts' were compared regarding incidence of difficult ETI, ability to predict difficult ETI, and decision for ETI. RESULTS: Mean years of professional experience were similar between the physician groups, but the median ETI experience differed significantly with 18/year for 'proficients' and 304/year for 'experts' (p<0.001). 'Proficient performers' intubated 130 of their 2170 treated patients (6.0%), while 'experts' did so in 146 of 1809 cases (8.1%, p=0.01 for difference). The incidence of difficult ETI was 17.7% for 'proficient performers', and 8.9% for 'experts' (p<0.05). In 4 cases ETI was impossible, all managed by 'proficient performers', but all patients could be ventilated sufficiently. Unexpected difficult ETI occurred in 6.1% for 'proficient performers', and 2.0% for 'experts' (p=0.08). CONCLUSIONS: In a prehospital setting 'expert' status was associated with a significantly lower incidence of 'difficult ETI' and a higher proportion of ETI decisions. In addition, ability to predict difficult ETI was higher, although non-significant. There was no difference in the incidence of impossible ventilation. PMID- 22040778 TI - Topical hemostatic agents in surgical practice. AB - Hemostasis is of critical importance in achieving a positive outcome in any surgical intervention. Different hemostatic methods can be employed and topical hemostatic agents are used in a wide variety of surgical settings. Procoagulation agents have different hemostatic properties and the choice of a specific one is determined by the type of surgical procedure and bleeding. Hemostatic treatments include fibrin sealants, microfibrillar collagen, gelatin hemostatic agents, oxidized regenerated cellulose and cyanoacrylates adhesives. Surgeons should be familiar with topical hemostatics to ensure an appropriate use. Our purpose is to illustrate the currently available agents, their mechanism of action and their effective applications, in order to ensure an optimal use in operating room. PMID- 22040779 TI - Effects of red blood cell transfusions on exercise tolerance and rehabilitation time after cardiac surgery. AB - Transfusions in cardiac surgery are associated with an increased morbidity and mortality rate. However, no information is available with respect to the recovery process of transfused patients after discharge from the hospital. Two-hundred seventeen patients who underwent cardiac surgery operations requiring packed red cells transfusions were studied during the rehabilitation stay. The exercise tolerance (6-min walk test) was not dependent on the number of packed red cells units transfused. Conversely, the length of stay in the rehabilitation hospital was independently associated (P=0.004) with the number of packed red cells transfused, with an increase of 0.6 days per each unit transfused. PMID- 22040780 TI - Molecular epidemiology of hepatitis C infection in Cyprus within the general population and high-risk cohorts. AB - BACKGROUND: Initial data on the molecular epidemiology of HCV infection in Cyprus showed a highly polyphyletic infection and multiple points of introduction into the general population. The continuation and expansion of this investigation is presented here including high risk groups. FINDINGS: The samples include additional subjects from the general population, a group of inmates and HIV/HCV coinfected individuals, whose strains were amplified by RT-PCR and sequenced in partial Core-E1 and NS5B regions. The results confirm the broad genotype distribution and polyphyletic infection on the island, and no new subtypes were found. Monophyletic clusters between strains of the prisoners and the injecting drug users imply sharing of infected equipment, and highlight the risk of widespread transmission in these cohorts, although no spill-over to the general population was observed. CONCLUSIONS: The results of this study underline the impact of population movements and high-risk population groups on the changing molecular epidemiology of HCV, with strains moving to Europe from Asia, Africa and Eastern Europe by means of immigration and modern transmission routes. PMID- 22040781 TI - Increased clopidogrel response is associated with ABCC3 expression: a pilot study. AB - BACKGROUND: The aim of this study was investigate the relationship between ABCB1 and ABCC3 gene expressions in peripheral blood cells (PBC) and the response to clopidogrel in patients with coronary arterial disease (CAD). METHODS: Twenty-six male CAD patients (50-70 years) under treatment with clopidogrel (75 mg/day) for at least 5 days were selected. Blood samples were obtained to evaluate platelet reactivity and ABCB1 and ABCC3 mRNA expression. Platelet reactivity was measured in P2Y12 Reaction Units (PRU) using VerifyNow. RNA was extracted from PBC and mRNA levels were measured by qPCR, using GAPD as a reference gene. RESULTS: Platelet response to clopidogrel was categorized in to PRU quartiles. Individuals with PRU values within the first quartile (Q1, <151 units) were considered good responders, while those who had PRU within the fourth quartile (Q4, PRU>260) were considered non-responders. ABCC3 was 1.7 times more expressed in Q4 than in Q1 PRU group (p=0.048). Moreover, CAD patients with low ABCC3 expression (Qe1, <2.5*10(-3)) had higher probability to have a good response to clopidogrel (OR: 18.00, 95%CI: 1.90-169.99, p=0.001). Univariate linear regression analysis demonstrated that low ABCC3 mRNA expression contributed with a reduction of 73 PRU in relation to the patients with expression value higher than 2.5*10(-3) (p=0.027). Neither ABCB1 mRNA levels nor clinical variables studied influenced PRU values. CONCLUSIONS: Low ABCC3 mRNA expression in peripheral blood cells is associated with increased clopidogrel response, but further studies are needed to describe the functional relationship of clopidogrel with the ABCC3. PMID- 22040782 TI - A competitive immunochromatographic strip assay for 17-alpha-hydroxy progesterone using colloidal gold nanoparticles. AB - BACKGROUND: A rapid and competitive immunochromatographic strip (ICS) test has been developed using colloidal gold as nanoprobe for measuring 17-alpha-hydroxy progesterone in serum which is a marker for congenital adrenal hyperplasia, an inborn error of metabolism. METHODS: Colloidal gold nanoparticles (NPs) were prepared by reducing chloroauric acid with sodium citrate. The corresponding protein conjugate was prepared by passive adsorption of 17-alpha-hydroxy progesterone-3-carboxymethyl-bovine serum albumin (17-OHP-3-CMO-BSA) immunogen on the colloidal gold surface. Both colloidal gold and its protein conjugates were characterized using standard techniques like transmission electron microscopy (TEM) and atomic force microscopy (AFM) in addition to the optical characterization. The test line antibody was raised against 17-alpha-hydroxy progesterone-BSA immunogen and control line antibody was raised against BSA in New Zealand white rabbits. RESULTS: This test antibody showed high immunoreactivity and specificity when characterized by ELISA for 17-alpha-hydroxy progesterone on microtiter plate. The primary antibody was coated on the nitrocellulose membrane as test line and anti-BSA antibody was coated as control line. The ICS test was developed in competitive assay format. The sensitivity of the present immunochromatographic strip assay was reported to be 2.5 MUg/l by visual observation. The signal at the test line was easily readable to the naked eye even at higher concentrations of 17-alpha-hydroxy progesterone normally associated with congenital adrenal hyperplasia. CONCLUSION: The present immunoassay takes 15 min for completion. There has not been any other lateral flow immunoassay for 17-alpha-hydroxy progesterone reported. PMID- 22040783 TI - Acetazolamide-challenged perfusion magnetic resonance imaging for assessment of cerebrovascular reserve capacity in patients with symptomatic middle cerebral artery stenosis: comparison with technetium-99m-hexamethylpropyleneamine oxime single-photon emission computed tomography. AB - OBJECTIVES: Acetazolamide-challenged perfusion magnetic resonance imaging (MRI) has been shown as a method for assessment of cerebrovascular reserve (CVR) capacity in patients with atherosclerotic steno-occlusive disease of internal carotid artery. We have assessed the feasibility of the acetazolamide-challenged perfusion MRI for evaluating CVR in symptomatic patients with severe middle cerebral artery (MCA) stenosis (>=70%) by comparison with the acetazolamide challenged technetium-99m-hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). METHODS: Seventeen prospectively enrolled patients with symptomatic unilateral MCA stenosis underwent technetium-99m hexamethylpropyleneamine oxime SPECT and perfusion MRI without and with acetazolamide challenge, respectively. Acetazolamide-challenged SPECT and perfusion MRI were compared quantitatively by Region of interest (ROI) analysis. RESULTS: At all ROIs, there were no significant differences in percent change between SPECT and perfusion MRI. Patients with impaired CVR showed significant decreases in the percent changes of respective cerebral blood flow (P=.016) and respective cerebral blood volume (P=.029). CONCLUSION: Acetazolamide-challenged perfusion MRI is feasible for evaluating CVR in symptomatic patients with severe MCA stenosis quantitatively. PMID- 22040784 TI - Radiologic-pathologic correlation in acute appendicitis: can we use it as a quality measure to assess interpretive accuracy of radiologists? AB - Radiologic-pathologic correlation was evaluated as a quality assurance tool by documenting error rates of 18 radiologists interpreting computed tomographic (CT) scans for acute appendicitis in 763 patients. The departmental error rate was 3.1%. Meaningful individual error rates could be determined in only the seven radiologists who interpreted >=30 CT scans for acute appendicitis. Radiologic pathologic correlation is an effective departmental monitor of interpretive accuracy, but individual accuracy can be assessed only for radiologists reading a large number of cases with pathologic proof. PMID- 22040785 TI - Taking advantage of chemical shift imaging: using opposed-phase images to locate the normal appendix on MR. AB - Multiple sequences of 50 consecutive adult pelvic MRI exams were retrospectively reviewed by two radiologists to determine if opposed-phase T1 gradient echo imaging can assist in locating the normal appendix on pelvic MRI. If the appendix was visualized, it was always seen on the T2 sequence, except for one exam. The opposed-phase sequence had the second highest visualization rate, and the appendix was identified the least on the post-gadolinium sequence. The presence of a "button nose" sign was also assessed and was present in one third of cases. PMID- 22040786 TI - Toxic megacolon in patients with severe acute colitis: computed tomographic features. AB - OBJECTIVE: The objective of the study was to evaluate computed tomography (CT) in the differential diagnosis of patients with toxic megacolon (TM) complicating severe acute colitis (SAC) and patients with SAC but no TM. MATERIALS AND METHODS: We identified 16 patients who presented clinically complicated SAC and CT examination before surgery. The CT scans of these patients were retrospectively evaluated in consensus by two abdominal radiologists blinded to the clinical and pathological results for CT findings of SAC, i.e., diffuse colonic wall thickening, submucosal edema, pericolonic fat stranding and ascites, and CT findings of TM reported in the literature, i.e., segmental colonic wall thinning, air-filled colonic distension over 6 cm with abnormal haustral pattern, nodular pseudopolyps and associated small bowel distension. Fisher's Exact Test was used for all statistical analyses. RESULTS: Segmental colonic wall thinning with abnormal haustral pattern was noted in TM only (P=.001). As compared to patients with SAC but no TM as a complication, patients with TM showed statistically more frequent air-filled colonic distension over 6 cm (P=.001) and nodular pseudopolyps (P=.001). Diffuse colonic wall thickening (P=.036) and submucosal edema (P=.036) were more present in cases of uncomplicated SAC. Pericolonic fat stranding (P=.12), ascites (P=.6), and small bowel and gastric distension (P=1) were not distinctive criteria. CONCLUSION: Computed tomography is useful in distinguishing patients with TM from patients with SAC but no TM as a complication. The association of air-filled colonic distension >6 cm, abnormal haustral pattern and segmental colonic parietal thinning seems pathognomonic of TM and should lead to rapid surgery. PMID- 22040787 TI - The negative impact of fatty liver on maximum standard uptake value of liver on FDG PET. AB - PURPOSE: The purpose of the study is to evaluate the impact of fatty liver on maximum standard uptake value (SUVmax) of liver on 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET). MATERIALS AND METHODS: A total of 173 consecutive healthy subjects were retrospectively recruited for analysis. Subjects with acute renal disease, chronic renal disease, or malignancy were excluded. Demographic data were collected from chart records. All subjects performed whole-body FDG PET, sonography of liver, and glutamic pyruvic transaminase (GPT) level. The SUVmax of liver on FDG PET was calculated. The relationship between the severity of fatty liver and SUVmax of liver on FDG PET was analyzed. RESULTS: There were significant differences in SUVmax of liver on FDG PET in four groups: no fatty liver, mild-degree, moderate-degree, and severe degree fatty liver on sonography diagnosis (P=.041). After adjusting for possible covariates age, sex, body mass index, and GPT, there was a significantly negative correlation between the severity of fatty liver and SUVmax of liver on FDG PET (beta=-.20, P<.001). CONCLUSION: Based on the results of this study, the liver cannot be used as a comparator of extrahepatic foci of equivocal increased FDG activity in patients with fatty liver disease. PMID- 22040788 TI - Retroportal main pancreatic duct with circumportal pancreas: radiographic visualization. AB - PURPOSE: The aim of this study was to investigate the imaging findings of retroportal main pancreatic duct (RMPD), a rare anomaly of the pancreas, and circumportal pancreas (CP) on computed tomography (CT) and magnetic resonance (MR) imaging. We also reviewed the previous literature and discussed its best imaging method, etiology and clinical importance. METHODS: This work is a retrospective study. Two cases of RMPD were enrolled. The imaging findings of RMPD and CP were reviewed among the various CT and MR images obtained. Differences in visualization among the scans were evaluated using a four-stage model. RESULTS: RMPD was always accompanied by CP. RMPD was detectable on contrast-enhanced CT but not on noncontrasted CT. RMPD was shown most clearly on arterial, portal and late phases of contrast-enhanced CT, contrast-enhanced fat suppressed T1-weighted images and fat-suppressed T2-weighted images. CP was much easier to detect than RMPD and could be identified even on noncontrasted images. CONCLUSIONS: We described the fourth and the fifth reported cases of RMPD. This is the first study to describe its MR imaging findings. CP was always present in cases of RMPD and was easily detectable on tomographic images. When radiologists or surgeons notice CP, it is necessary to pay attention to the course of the main pancreatic duct, particularly preoperatively to avoid surgical complications. It should be noted that these anomalies are undetectable on projection images. PMID- 22040789 TI - Evaluating the perfusion of occupying lesions of kidney and bladder with contrast enhanced ultrasound. AB - PURPOSE: To evaluate the clinical diagnostic value of contrast-enhanced ultrasound (CEUS) for occupying lesions of kidney and bladder. MATERIALS AND METHODS: CEUS was performed for a total of 50 kidney and bladder occupying lesions in 47 cases, and CEUS manifestations of these lesions were observed and analyzed. Patterns of dynamic changes in perfusion phases of CEUS were summarized and compared with results of postoperative pathology, enhanced computed tomography (CT), magnetic resonance imaging (MRI), and follow-ups. RESULTS: CEUS results showed that there were 22 cases of malignant renal tumors, 11 cases of benign lesions, two cases of renal column hypertrophy, and 12 cases of malignant bladder tumors (15 lesions). Renal cell carcinoma exhibited various CEUS manifestation, with the majority showing fast filling and hyper-enhancement. CEUS manifestation of renal hamartoma was characterized by slow filling and slow outflow. Renal cystic lesions always exhibited no enhancement within the cysts. Renal column hypertrophy exhibited the same enhancement pattern as the renal cortex. CEUS manifestation of bladder carcinoma was mainly characterized by quick filling, quick outflow, and hyperenhancement. CONCLUSIONS: CEUS offers real-time observation of perfusion in occupying lesions of kidney and bladder, but the enhancement pattern of kidney occupying lesions was complex; therefore, combination of enhanced CT, MRI, and CEUS may be necessary. PMID- 22040790 TI - Multimodality imaging of melanoma metastases to the abdomen and pelvis. AB - Disease in the abdomen and pelvis is frequent in patients with metastatic melanoma (MM). Multidetector row computed tomography is the imaging modality of choice for diagnosis and follow-up of MM. However, positron emission tomographic scan may be used as well as other newer imaging modalities, particularly for imaging of the abdominal and pelvic metastases. The aim if this exhibit is to review the distribution and features of melanoma metastases to the abdomen and pelvis as well as the role of currently available imaging modalities. PMID- 22040791 TI - MRI findings of sarcomatoid renal cell carcinoma in nine cases. AB - PURPOSE: To assess the magnetic resonance imaging (MRI) features of a series of 9 cases of pathologically proven sarcomatoid renal cell carcinoma (SRCC). METHODS: Two radiologists in consensus retrospectively reviewed a spectrum of MRI features of nine cases of SRCC imaged at our institution between 2003 and 2009. RESULTS: SRCC had a mean diameter of 9.9 cm. All cases had an irregular or infiltrative morphology and demonstrated heterogeneous T2 signal intensity and enhancement. Internal necrosis was present in all cases, with four cases demonstrating >50% necrosis. Evidence of aggressive local behavior and/or distant spread was frequently observed. CONCLUSIONS: We have presented the largest case series to our knowledge of the MRI appearance of SRCC, with the lesions tending to appear as large heterogeneous masses with internal necrosis and evidence of aggressive local or distant behavior. However, these imaging features are non-specific, and histology remains necessary to establish the diagnosis. PMID- 22040792 TI - Sacroiliac joint vacuum phenomenon--underreported finding. AB - BACKGROUND AND PURPOSE: Vacuum phenomenon (VP) is commonly found in sacroiliac joints, and its significance in patients with back pain has been debated. We investigated the prevalence of sacroiliac joint vacuum phenomenon (SJVP) and the rate at which it is reported on abdominopelvic and lumbosacral spine computed tomography (CT) images by body imagers and neuroradiologists. We hypothesized that it would be more common than not and that neuroradiologists would identify it more frequently than body imagers and on spine images more commonly than abdominopelvic studies due to the search for the source of back pain in the former. MATERIALS AND METHODS: CT images of the pelvis and lumbar spine from January to February 2009 were retrospectively reviewed. Six hundred fifty-two patients were studied during this period. Axial thin-section images were reviewed under default lung and bone window settings. Age, sex, and radiologist reports were assessed from electronic medical records. RESULTS: The prevalence of SJVP on CT imaging was 34%, with higher rates found in female (41%, P<.001) and older (39%, P<.05) patients. Eighty-five percent of the phenomena were present bilaterally. Among the 223 patients with SJVP, only 17% were reported. There were no statistically significant differences between reporting rates for body radiologists and neuroradiologists. CONCLUSION: SJVP is a prevalent condition with higher rates among older and female individuals. The phenomenon is underreported on CT images whether the studies performed are abdominopelvic scans or spine studies and whether they are interpreted by body imagers or neuroradiologists. PMID- 22040793 TI - Suspiciously malignant findings on ultrasound after fine needle aspiration biopsy in a thyroid nodule with initially benign ultrasound and cytologic result: to repeat or to follow-up. AB - PURPOSE: The purposes of this study were to evaluate the incidence of suspiciously malignant change on ultrasound (US) in thyroid nodules after initial benign US and cytologic results and to investigate the associated US characteristics and the management of these nodules. MATERIALS AND METHODS: Among the patients who underwent thyroid fine needle aspiration biopsy (FNAB) from October 2003 to December 2004, 550 patients who had thyroid nodules with initial benign US and cytologic results were included. Reference standards were established by pathologic results, follow-up cytologic results or follow-up US. We evaluated the incidence of morphologic changes to suspiciously malignant US findings of these thyroid nodules after FNAB. We also evaluated the initial US features associated with the nodules showing suspiciously malignant findings on US after FNAB in these patients. RESULTS: Of 550 patients, 28 nodules (5.1%) showed morphologic changes into nodules with suspiciously malignant US findings on follow-up US. All thyroid nodules showing morphologic changes had mixed solid and cystic components (P<.001). Suspiciously malignant changes on US were associated with the percentage of the cystic portion, but all changed nodules were confirmed as benign. CONCLUSION: Follow-up US should be recommended rather than to repeat FNAB for thyroid nodules with initial benign US and cytologic results even if they later develop suspiciously malignant US features after FNAB. PMID- 22040794 TI - PET-CT in the diagnosis of localized malignant pleural mesothelioma. AB - A 67-year-old man presented with right-sided chest and shoulder pain. Chest roentgenogram demonstrated a right upper zone shadow. Computed tomography (CT) revealed a pleural mass and adjacent chest wall disease. Image-guided percutaneous biopsy suggested malignant mesothelioma. We describe the use of 18 fluorodeoxyglucose-positron emission tomography (PET-CT) in the diagnosis and management of localized malignant mesothelioma. PMID- 22040795 TI - Uterine inversion caused by a submucous leiomyoma. AB - Uterine inversion secondary to a pathological process of the myometrium is very rare. We report the case of a woman presenting with a submucosal pedunculated leiomyoma in whom a study by 3-T magnetic resonance imaging (MRI) demonstrated a uterine inversion. The MRI findings were characteristic and permitted a correct diagnosis before the surgical intervention. PMID- 22040796 TI - Primary seminal vesicle adenocarcinoma. AB - We describe the case of a 48-year-old male with primary seminal vesicle carcinoma. Although most malignant lesions involving the seminal vesicles are the result of secondary spread from other tumors, primary seminal vesicle carcinoma must be considered in the differential diagnosis, as the prognosis for this condition is dismal. Magnetic resonance imaging plays a crucial role in assessment, as it can exquisitely depict the anatomy of this region and define the extent of a seminal vesicle lesion. PMID- 22040797 TI - Radiologic-pathologic findings of primary osseous adamantinoma with unusual metastasis to the posterior cul-de-sac in pregnancy. AB - Adamantinoma is a rare primary bone malignancy with a predilection for the tibial cortex. Metastases have been reported to the long bones, lung, pleura and spine. We present a 26-year-old pregnant woman with metastatic disease to the posterior cul-de-sac, lungs, liver and retroperitoneum, which collectively have not been previously reported in a single patient to our knowledge. PMID- 22040799 TI - Selective recovery of gold from waste mobile phone PCBs by hydrometallurgical process. AB - The leaching of gold from the scrap mobile phone PCBs by electro-generated chlorine as an oxidant and its recovery by ion exchange process was investigated. The leaching experiments were carried out by employing separate leaching reactor connected with the anode compartment of a Cl(2) gas generator. The leaching of gold increased with increase in temperature and initial concentration of chlorine, and was favorable even at low concentration of acid, whereas copper leaching increased with increase in concentration of acid and decrease in temperature. In a two-stage leaching process, copper was mostly dissolved (97%) in 165 min at 25 degrees C during the 1st stage leaching in 2.0 mol/L HCl by electro-generated chlorine at a current density of 714A/m(2) along with a minor recovery of gold (5%). In the 2nd stage gold was mostly leached out (93% recovery, ~67 mg/L) from the residue of the 1st stage by the electro-generated chlorine in 0.1 mol/L HCl. Gold recovery from the leach liquor by ion exchange using Amberlite XAD-7HP resin was found to be 95% with the maximum amount of gold adsorbed as 46.03 mg/g resin. A concentrated gold solution, 6034 mg/L with 99.9% purity was obtained in the ion exchange process. PMID- 22040798 TI - Isoflurane postconditioning induces neuroprotection via Akt activation and attenuation of increased mitochondrial membrane permeability. AB - We have shown that isoflurane application at the onset of reperfusion (postconditioning) reduces brain ischemic injury in rats. This study was designed to determine whether this protection involved activation of prosurvival protein kinases and maintenance of normal mitochondrial membrane permeability. Two-month old male rats were subjected to a 90-min middle cerebral arterial occlusion. They then were exposed or were not exposed to 2% isoflurane for 1 h. Ischemic penumbral cerebral cortex was harvested immediately and separated into the mitochondrial and cytosolic fractions. We showed that the mitochondrial nicotinamide adenine dinucleotide content in the ischemic penumbral cortex was significantly reduced, suggesting an increased mitochondrial membrane permeability. This increase was partly attenuated by isoflurane postconditioning. The mitochondrial adenosine diphosphate content in the penumbral cortex was reduced no matter whether the animals were postconditioned with isoflurane. The mitochondrial adenosine triphosphate concentration was not different among various experimental conditions. The phospho-Akt in the cytosolic and mitochondrial fractions of the ischemic penumbral cortex was higher than that in the control cortex. This increase trended to be higher in animals with isoflurane postconditioning. A similar change pattern was observed in the mitochondrial phospho-glycogen synthase kinase 3beta, an Akt substrate that can regulate the mitochondrial membrane permeability. Isoflurane postconditioning reduced oxygen glucose deprivation-induced injury of rat cortical neuronal cultures and increased phospho-Akt in these cells. The isoflurane postconditioning-induced protection in the neuronal cultures was decreased by the Akt inhibitor LY294002. These results suggest that isoflurane postconditioning effects may be mediated by Akt and involve reduced mitochondrial membrane permeability. PMID- 22040800 TI - Removal of methylene blue from aqueous solution with magnetite loaded multi-wall carbon nanotube: kinetic, isotherm and mechanism analysis. AB - In this study, we have demonstrated the efficient removal of cationic dye, methylene blue (MB), from aqueous solution with the one-pot solvothermal synthesized magnetite-loaded multi-walled carbon nanotubes (M-MWCNTs). The as prepared M-MWCNTs were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The effects of contact time, initial dye concentration, and solution pH on the adsorption of MB onto M-MWCNTs were systematically studied. It was shown that the MB adsorption was pH-dependent. Adsorption kinetics was best described by the pseudo-second-order model. Equilibrium data were well fitted to the Langmuir isotherm model, yielding maximum monolayer adsorption capacity of 48.06 mg g(-1). FTIR analysis suggested that the adsorption mechanism was possibly attributed to the electrostatic attraction and pi-pi stacking interactions between MWCNTs and MB. PMID- 22040801 TI - Electron microscopy studies of nucleosome remodelers. AB - ATP-dependent chromatin remodeling complexes, or remodelers, are large protein assemblies that use the energy from ATP hydrolysis to non-covalently modify the structure of nucleosomes, playing a central role in the regulation of chromatin dynamics. Our understanding of the mechanism and regulation of this remodeling activity and the diversity of products that chromatin remodelers can generate remains limited, partly because very little structural data are available on these challenging samples. Electron microscopy (EM) and single-particle approaches have made inroads into the structural characterization of a number of remodeling complexes. Here I will review the work done to date, focusing on functional insights we have gained from these structures. PMID- 22040802 TI - Binding phylacteries: mind and body meet in the operating room. PMID- 22040804 TI - Circadian variation in ghrelin and certain stress hormones in crib-biting horses. AB - Crib-biting is classified as an oral stereotypy, which may be initiated by stress susceptibility, management factors, genetic factors and gastrointestinal irritation. Ghrelin has been identified in the gastric mucosa and is involved in the control of food intake and reward, but its relationship to crib-biting is not yet known. The aim of this study was to examine the concentration and circadian variation of plasma ghrelin, cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin in crib-biting horses and non-crib-biting controls. Plasma samples were collected every second hour for 24h in the daily environment of eight horses with stereotypic crib-biting and eight non-crib-biting controls. The crib-biting horses had significantly higher mean plasma ghrelin concentrations than the control horses. The circadian rhythm of cortisol was evident, indicating that the sampling protocol did not inhibit the circadian regulation in these horses. Crib biting had no statistically significant effect on cortisol, ACTH or beta endorphin concentrations. The inter-individual variations in beta-endorphin and ACTH were higher than the intra-individual differences, which made inter individual comparisons difficult and complicated the interpretation of results. Further research is therefore needed to determine the relationship between crib biting and ghrelin concentration. PMID- 22040805 TI - Mycobacterial infections in multiple species: implications for diagnosis and control. PMID- 22040803 TI - MVP and vaults: a role in the radiation response. AB - Vaults are evolutionary highly conserved ribonucleoproteins particles with a hollow barrel-like structure. The main component of vaults represents the 110 kDa major vault protein (MVP), whereas two minor vaults proteins comprise the 193 kDa vault poly(ADP-ribose) polymerase (vPARP) and the 240 kDa telomerase-associated protein-1 (TEP-1). Additionally, at least one small and untranslated RNA is found as a constitutive component. MVP seems to play an important role in the development of multidrug resistance. This particle has also been implicated in the regulation of several cellular processes including transport mechanisms, signal transmission and immune responses. Vaults are considered a prognostic marker for different cancer types. The level of MVP expression predicts the clinical outcome after chemotherapy in different tumour types. Recently, new roles have been assigned to MVP and vaults including the association with the insulin-like growth factor-1, hypoxia-inducible factor-1alpha, and the two major DNA double-strand break repair machineries: non-homologous endjoining and homologous recombination. Furthermore, MVP has been proposed as a useful prognostic factor associated with radiotherapy resistance. Here, we review these novel actions of vaults and discuss a putative role of MVP and vaults in the response to radiotherapy. PMID- 22040806 TI - Overexpression of histidine-rich calcium binding protein in equine ventricular myocardium. AB - Histidine-rich calcium binding protein (HRC) is a high capacity, low affinity Ca(2+) binding protein, specifically expressed in striated muscles of mammals. In rabbit skeletal and cardiac muscles, HRC binds to sarcoplasmic reticulum (SR) membranes via triadin, a junctional SR protein. Recently, a potential role in heart failure and arrhythmogenesis has been assigned to HRC due to its activity as regulator of SR Ca(2+) uptake and Ca(2+) release. HRC might play a particularly relevant role in the equine heart, given its slower resting heart rate (20-35 beats/min) and longer action potential duration (APD) (0.6-1.0 s) than are found in other mammals. The results from this study showed for the first time direct evidence that HRC protein in equine cardiac muscle was expressed in association with the SR membranes and that HRC transcriptional activity was three times higher in the ventricles compared to the atria. The predominance of HRC mRNA up-regulation in ventricular myocardium was specific to the horse heart, since a more even distribution between atria and ventricles was found in animals of similar body size or species, such as cattle or domestic donkeys. PMID- 22040807 TI - The effect of rosiglitazone on LRP1 expression and amyloid beta uptake in human brain microvascular endothelial cells: a possible role of a low-dose thiazolidinedione for dementia treatment. AB - Thiazolidinediones, such as rosiglitazone or pioglitazone, are anti-diabetic agents that have been expected to show a beneficial effect in Alzheimer's disease (AD) because of their anti-inflammatory effect. However, these agents have failed to show a significant beneficial effect on AD in recent clinical trials. Here, we suggest that low-dose rosiglitazone treatment, and not the conventional doses, has an amyloid beta (Abeta)-clearing effect by increasing LRP1, an Abeta outward transporter in the blood-brain barrier. Rosiglitazone up-regulated LRP1 mRNA and protein expression and LRP1 promoter activity in human brain microvascular endothelial cells (HBMECs). Abeta uptake through LRP1 in HBMECs was also increased by rosiglitazone. This increase in LRP1 and Abeta uptake was observed in up to 10 nm rosiglitazone concentration. At concentrations above 20 nm rosiglitazone, the LRP1 expression and Abeta uptake in HBMECs were not altered. The possible mechanism of this unusual dose response is discussed. This study suggests a new therapeutic application of thiazolidinediones for AD at a much lower dose than the doses used for diabetes treatment. PMID- 22040808 TI - Endoscopic treatment of glottic stenosis: a report on the safety and efficacy of CO2 laser. AB - BACKGROUND: Treatment of glottic stenosis is a considerable challenge to the otolaryngologist. Glottic airway patency can be compromised by bilateral vocal fold palsy, anterior webbing or a posterior segment scar, which may be significant enough to impair arytenoid movement. METHOD: A retrospective analysis of a prospective database of patients (n = 34) treated by a specialist airway surgeon. All patients underwent endoscopic treatment with a CO(2) laser in an attempt to improve airway calibre and, in 12 patients, to decannulate tracheostomy tubes. RESULTS: Twenty-one patients had bilateral vocal fold palsy and 13 had predominantly posterior glottic stenosis. A variety of pathology directed treatment approaches were used to achieve good functional results. Four patients required a second endoscopic procedure. The overall revision rate was 5 per cent for bilateral fold palsy and 23 per cent for posterior glottic stenosis (p < 0.05). All patients had an adequate functional airway calibre, and all 12 tracheotomised patients were decannulated. DISCUSSION: Pathology-directed endoscopic laser surgery is safe and effective treatment for glottic stenosis. Rather prescriptive use of unilateral or bilateral cordotomy or combined cordo arytenoidectomy, clinicians must perform the procedure that will treat the lesion most adequately. Our success rate compared favourably with the best reported results. PMID- 22040809 TI - Interference by o-phenanthroline in the radioimmunoassay of angiotensin II in small volume blood samples. AB - OBJECTIVES: To investigate the ratio of enzyme inhibitor volume to blood volume in angiotensin II (Ang II) blood collection tubes. DESIGN AND METHODS: Whole blood was mixed with known volumes of inhibitor prior to angiotensin II analysis. RESULTS: Imunoreactive Ang II levels increased at low blood volume to high inhibitor volume ratios, due to interference by o-phenanthroline. CONCLUSION: To prevent falsely elevated Ang II levels in low volume blood samples an appropriate volume of inhibitor solution must be used. PMID- 22040810 TI - Homozygous bisalbuminemia or homozygous mutant albumin? AB - INTRODUCTION: Bisalbuminemia is a genetic condition in which an albumin variant is found in serum in addition to normal albumin. METHODS AND MATERIALS: Serum protein electrophoresis using the Sebia HYDRASYS electrophoresis system was performed on an 84 year old male. RESULTS: Serum protein electrophoresis showed a single albumin band migrating faster than normal albumin. CONCLUSION: The presence of a homozygous albumin variant band, albumin Naskapi, is noted. PMID- 22040811 TI - Molar expression: Interconverting results of highly sensitive troponin I and T while preserving clinical significance. PMID- 22040812 TI - Comparison of tear proteins between healthy and early diabetic retinopathy patients. AB - OBJECTIVES: To identify potential prognostic or diagnostic marker tear proteins for early diabetic retinopathy (DR) and to investigate the pathogenesis of this disease using proteomics techniques. DESIGN AND METHODS: The tear proteins expressed in patients suffering from diabetes mellitus without the retinopathy symptoms, nonproliferative diabetic retinopathy and healthy volunteers were analyzed by 2-DE. The differentially expressed proteins in patients were identified by ESI-Q-TOF and confirmed by Western blotting. RESULTS: Proteins which were differentially expressed with statistical significance (P<0.05) in two diabetic groups as compared to those in healthy group were selected and identified by ESI-Q-TOF MS/MS. Among these proteins, three proteins (LCN-1, HSP27 and B2M) were found to exhibit a progressive reduction in two disease groups. The expression levels of which might be useful as diagnostic biomarkers of DR were verified by Western blotting CONCLUSIONS: Proteomic analysis using tear is a novel approach that can provide insight into possible biomarker and the pathogenesis of early DR. PMID- 22040813 TI - Causes of rejection of blood samples handled in the clinical laboratory of a University Hospital in Porto Alegre. AB - OBJECTIVE: Errors in clinical laboratories have a great impact on safety and care of patients. The pre-analytical phase is responsible for about 70% of errors. Hence, the objective was to determine what types of pre-analytical errors for improvements at this stage, and contribute data to the literature. DESIGN AND METHODS: Every three months during the study, the rejected blood samples were assessed for type of pre-analytical error and home care. RESULTS: 77,051 blood samples were collected in the search period, whereof 441 (0.57%) were rejected by some type of pre-analytical error and therefore had to be recollected. Clot was found to be the major cause of rejection of samples, 43.8%, followed by insufficient sample volume, 24%. CONCLUSION: This study has shown that the most frequent causes of pre-analytical errors and rejection of samples corroborate those found in the literature. PMID- 22040814 TI - Association of single nucleotide polymorphisms in IL-12 and IL-27 genes with colorectal cancer risk. AB - OBJECTIVES: Interleukin-12 (IL-12) plays an important role in antitumor immunity. Interleukin-27 (IL-27) is a novel IL-12 family member. The present studies demonstrate that IL-27 mediates potent antitumor activity. However, No studies have examined the association of these polymorphism with colorectal cancer (CRC). Therefore, we investigated the relationship of IL-12 and IL-27 gene polymorphisms and CRC. DESIGN AND METHODS: We analyzed polymorphisms of IL-12 gene 16974 A/C and IL-27 gene -964 A/G, 2905 T/G, 4730 T/C in 410 patients with CRC and 450 controls, using PCR-RFLP method. RESULTS: There were no significant differences in the genotype and allele frequencies of IL-12 and IL-27 gene polymorphisms between the group of patients with CRC and the controls. Furthermore, no association was found between IL-12 family gene polymorphisms and different clinical stages in patients with CRC. CONCLUSION: These findings suggest that IL 12 and IL-27 gene polymorphisms may not be involved in susceptibility to CRC. PMID- 22040815 TI - Serum uric acid levels and the clinical characteristics of depression. AB - OBJECTIVE: This study was designed to investigate the correlation between serum uric acid (UA) levels and the clinical characteristics of depression. DESIGN AND METHODS: The serum UA levels were measured in 124 patients with depression, 660 patients with different types of other mental disorders (OMD) and 42 healthy subjects. Clinical characteristics of depression and OMD were also investigated. RESULTS: Depressive patients (271.97 +/- 77.50 MUmol/L) had significantly lower UA levels than those with delirium, dementia, amnesia and other cognitive disorders (339.95 +/- 141.74 MUmol/L, P=0.004), substances related disorders (359.61 +/- 125.02 MUmol/L, P=0.022), schizophrenia (341.03 +/- 106.84 MUmol/L, P=0.000), schizoaffective disorder (336.78 +/- 155.49 MUmol/L, P=0.024), bipolar disorder (323.04 +/- 108.70 MUmol/L, P=0.008) and the healthy control group (315.76 +/- 87.50 MUmol/L, P=0.012). We also found that the UA levels of depressive patients normalised after a five week treatment with antidepressants. CONCLUSION: Our data suggested that a lowered UA level is another characteristic of depression. PMID- 22040816 TI - [Frontiers in vitamin D; basic research and clinical application. Vitamin D deficiency, insufficiency and sufficiency]. AB - In November 2010, IOM (Institute of Medicine) of USA issued a report on DRI (Dietary Reference Intakes) for calcium and vitamin D, which challenged then widespread view among many in US that vitamin D sufficiency is defined by serum 25 (OH) D level more than 30 ng/mL. The IOM report concluded serum 25 (OH) D level of 20 ng/mL would be sufficient for 97.5% of general healthy population, and recommended vitamin D intake much lower than that had been believed among many experts. After much discussion, disputes, in July 2011, American Endocrine Society issued a guideline for Vitamin D deficiency, which contrasted to IOM report in many aspects. In this article, differences between those two guidelines are reviewed and current issues surrounding vitamin D deficiency/sufficiency are discussed. PMID- 22040817 TI - [Frontiers in vitamin D; basic Research and clinical application. Effect of active vitamin D3 on osteoporosis]. AB - Although active vitamin D3 only slightly increases bone mineral density (BMD) , it prevents fractures to a greater extent than is predicted, based on measurements of BMD. This effect is partly attributed to enhanced muscle strength and increased physical capabilities by vitamin D, which, in turn, decreases the risk of falls and fractures. In addition, active vitamin D3 has been reported in animal studies to improve bone quality by enhancing trabecular bone microarchitecture and increasing enzymatic collagen cross-links in bone. A (large scale of) randomized controlled trial in Japanese postmenopausal women verified that the combination therapy of bisphosphonate (alendronate) plus active vitamin D3 was more effective than monotherapy in terms of fracture prevention in high fracture risk group. PMID- 22040818 TI - [Frontiers in vitamin D; basic research and clinical application. Vitamin D and secondary hyperparathyroidism]. AB - In chronic kidney disease (CKD) , phosphate retention and low 1, 25 dihydroxyvitamin D [1, 25 (OH) 2D] due to a decrease in the number of functioning nephrons had long been considered to contribute to the pathogenesis of secondary hyperparathyroidism (SHPT) . The discovery of fibroblast growth factor 23 (FGF23) drastically changed our understanding and provided new implication of the development of SHPT. In addition, CKD impairs the maintenance of normal 25 hydoxyvitamin D [25 (OH) D] levels which can act directly on the parathyroid glands to repress PTH synthesis. Active vitamin D therapy is widely used for the treatment of SHPT. However, the active form of vitamin D, 1, 25 (OH) 2D and its analogs increase the calcium and phosphate levels by increasing the intestinal calcium and phosphate absorption. To suppress PTH secretion without these potential complications, several vitamin D analogs including paricalcitol, maxacalcitol and doxercalciferol are already in clinical use. A novel therapeutic concept in new vitamin D therapies are expected to improve patient outcome. PMID- 22040819 TI - [Frontiers in vitamin D; basic research and clinical application. Activated vitamin D in psoriasis]. AB - Psoriasis is a chronic immune-mediated disease that appears on the skin. It occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms. Activated vitamin D3 is the first-line treatment for psoriasis. Psoriasis is often treated with combination therapy of activated vitamin D3 and other treatment. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Thus, the goal for the treatment of psoriasis is to control the signs and symptoms over a long period and to ameliorate the quality of life of psoriasis patients. PMID- 22040820 TI - [Frontiers in vitamin D; basic research and clinical application. Is VDR a factor of bone volume regulator in bone tissues?]. AB - Vitamin D is one of the best established hormone to exert beneficial action for bone mass control and bone metabolism. Such vitamin D action for bone tissue is recapitulated in intact animals, while vitamin D is well known to potentiate bone resorption by inducing gene of RANKL an osteoclastic inducer. By genetic characterization of VDR in mice, VDR was found to serve as a negative regulator in intact bone. Moreover, RANKL gene expression level in intact bone was down regulated in osteoblast-specific VDR KO mice. Thus, these findings indicate that VDR in bone tissue is a negative regulator for bone mass control. PMID- 22040821 TI - [Frontiers in vitamin D; basic research and clinical application. Exploratory research, biological characteristic and pharmacokinetics of eldecalcitol, a new active vitamin D derivative]. AB - In 1981 when a clinical application of alfacalcidol, a prodrug of active vitamin D, started, differentiation inducing properties of active vitamin D were found at the same year. This indicated the diversity of the physiological actions of active vitamin D, which initially had been thought only to contribute to bone and calcium metabolism. Because these physiological actions were clinically useful, the discovery revealed opportunities for the development of drugs appropriate to specific purpose by synthesizing derivatives to separate biological effects. Several active vitamin D derivatives are now commercially available and contributing to current clinical practice in the fields of psoriasis and secondary hyperparathyroidism treatments. Eldecalcitol was also joined into clinically useful derivatives as a new drug for the treatment of osteoporosis in this year. In this chapter, exploratory research, biological characteristic and pharmacokinetics including putative metabolites based on structural appearances of eldecalcitol are introduced. PMID- 22040823 TI - [Frontiers in vitamin D; basic research and clinical application. Vitamin D and falls]. AB - Along with aging, the synthesis of vitamin D3 in the skin declines with insufficient sunlight exposure, leading to vitamin D deficiency. In the elderly, vitamin D deficiency results not only in impaired bone mineralization, but also myopathy. Low vitamin D has also been shown to be associated with decline of muscle strength, sarcopenia, functional limitation, and disability. Several recent studies have shown that low serum vitamin D concentration is associated with lower physical function and falls in older adults. The previous study of Japanese community elderly aged 65 years and older has also shown that low serum 25-hydroxyvitamin D [25 (OH) D] level is significantly associated with inferior physical performance and experience of fall. In this chapter, a prospective follow-up study conducted to clarify the association between serum 25 (OH) D level and the risk of falls is introduced. The subjects were the community dwelling elderly women aged 75 years or older (n = 1,393) who participated in a mass health examination. The baseline prevalence of 25 (OH) D insufficiency [blood level<20 ng/mL] was 35.2%. In a multiple logistic regression model adjusted for age, women in the lowest tertile of 25 (OH) D (<= 19 ng/mL) were at significantly higher risk of any fall (OR = 1.56 ; 95% CI = 1.14-2.14 ; p = 0.005) and recurrent fall (OR = 1.75 ; 95% CI = 1.15-2.68, p = 0.010) compared to women in the highest tertile [25 (OH) D >= 25 ng/mL] . A multiple logistic regression model adjusted for various confounding variables showed that serum 25 (OH) D level was independently associated with the risk of falls (p = 0.023) . In conclusion, these results indicate that lower 25 (OH) D, particularly levels below 20 ng/mL, is independently and significantly associated with an increased risk of falling. PMID- 22040822 TI - [Frontiers in vitamin D; basic research and clinical application. A review on histological findings in bones administered with eldecalcitol]. AB - This review will show the histological findings in femora of ovariectomized (OVX) rats administered with or without eldecalcitol, a second-generation of vitamin D analog, which were published in our recent article. The OVX group showed markedly reduced bone mineral density, and the decreased trabecular number and thickness, which was consistent to increased osteoclastic number and bone resorption parameters. After eldecalcitol administration, the number of osteoclasts was diminished, accompanied with elevated bone mineral density. Interestingly, eldecalcitol did promote a type of focal bone formation that is independent of bone resorption, a process known as bone mini-modeling. Taken together, our findings suggest that eldecalcitol mainly inhibits osteoclastic bone resorption, but, in part, stimulates focal bone formation in the OVX bone. PMID- 22040824 TI - [Frontiers in vitamin D; basic research and clinical application. Vitamin D regulation of macrophage -dependent innate immunity]. AB - Among various pleiotropic actions of vitamin D, its immunomodulatory role has been well recognized for more than 30 years. However, despite the presence of vitamin D receptors in immune cells including lymphocytes and monocytes/macrorphages, the impact of vitamin D system on immune regulation remained unclear. Recently, two key functions of vitamin D : induction of antimicrobial peptides and autophagy in cells of the monocyte/macrophage lineage, have been described, revealing a much clearer picture of the role of vitamin D as an immunomodulator, particularly in innate immunity against pathogens such as Mycobacterium tuberculosis. This review summarizes recent advances in research of vitamin D as a regulator of innate immunity, and clinical trials of vitamin D as a potential anti-infectious agent. PMID- 22040825 TI - [Frontiers in vitamin D; basic research and clinical application. Inhibitory effects of eldecalcitol, an active vitamin D derivative, on bone resorption in vivo]. AB - Eldecalcitol is a new vitamin D(3) derivative recently approved for the treatment of osteoporosis in Japan. Previous studies showed that daily administration of eldecalcitol increased bone mineral density (BMD) by suppressing bone resorption in animals and in patients with osteoporosis. We examined how eldecalcitol suppresses bone resorption in vivo . Daily administration of eldecalcitol into mice did not affect properties of osteoclast precursors, but suppressed RANKL expression in bone. These results suggest that daily administration of eldecalcitol increase BMD by suppressing RANKL expression in bone. PMID- 22040826 TI - [Frontiers in vitamin D; basic research and clinical application. Eldecalcitol: the effect on bones and calcium metabolism]. AB - Eldecalcitol is a new active vitamin D3 compound, bearing a hydroxypropyloxy residue at the 2beta-position of 1alpha, 25 (OH) 2D3. In ovariectomized rats, eldecalcitol increased vertebral bone mass and bone strength by inhibiting bone resorption and maintaining bone formation. In randomized, placebo-controlled, double-blinded clinical trial for osteoporotic subjects, eldecalcitol increased lumber vertebral and hip bone mineral density independent of vitamin D status. Furthermore, in patients with osteoporosis, eldecalcitol treatment was associated with a lower risk of vertebral and wrist fractures, with greater decrease in bone turnover markers compared with alfacalcidol. The incidence of adverse events was similar between the two treatments. Therefore, eldecalcitol can become a new treatment of choice for osteoporosis. PMID- 22040827 TI - [Frontiers in vitamin D; Basic research and clinical application. The effects of eldecalcitol on bone mineral density and fracture prevention--Post hoc analysis]. AB - We conducted a post-hoc analysis of the phase III clinical trial of eldecalcitol (in comparison with alfacalcidol) . Enrolled subjects were divided into subgroups according to age, vitamin D levels, prevalent vertebral fractures, and baseline lumbar bone mineral density (LBMD) . In the eldecalcitol group, LBMD increased more than 3% in 3 years, which was significantly higher than that in the alfacalcidol group in all 4 subgroups. Incidence of new vertebral fractures was lower in the eldecalcitol group than in the alfacalcidol group in each of the first 3 subgroups, and the difference between eldecalcitol and alfacalcidol was significant in the age group of 70 years and over. When we compared the fracture risk with the placebo group reported in the minodronic acid phase III fracture prevention trial, the reductions in relative risk in the alfacalcidol and eldecalcitol group were about 30% and 50%, respectively (not direct comparisons) . Eldecalcitol is beneficial for a wide range of patients with osteoporosis, since its effects of increasing BMD and preventing fractures were not impaired by age, vitamin D levels, prevalent vertebral fractures, or baseline BMD. PMID- 22040828 TI - [Frontiers in vitamin D; Basic research and clinical application. Effect of eldecalcitol on bone structure]. AB - Eldecalcitol, a new active vitamin D compound, has revealed to have its superiority to alfacalcidol in preventing vertebral fractures in osteoporotic subjects, as well as in preventing major non-vertebral fracture. Several animal studies demonstrated the greater efficacy in bone metabolism comparing the traditional active vitamin D, partly in relation to improvement of trabecular bone microstructure ; increase in BV/TV, Tb.N and Tb.Th, and decrease in Tb.Sp. Furthermore, three years longitudinal observation of hip geometry and biomechanical properties using clinical CT (multi-detector row CT) has disclosed an unexpected potential of eldecalcitol to improve biomechanical parameters by the increase in cortical cross-sectional area, cortical bone mass, and cortical perimeter, and by maintaining clinical thickness, probably through a more potent effect of eldecalcitol in mitigating endocortical bone resorption compared to alfacalcidol. PMID- 22040829 TI - [Calcium Pros and Cons--Which method is useful for diagnosis of vertebral body fracture; radiograph or MRI?--Vertebral radiograph is the useful method for diagnosis and monitoring of vertebral body fractures]. AB - Vertebral radiograph is very useful to assess the vertebral body fracture and the severity of deformity due to fracture. To decrease the severity of vertebral body fracture deformity, treatment should be started as soon as possible after diagnosis. We can diagnose the early stage of vertebral body fracture to get the special findings on radiographs. Furthermore, the process of fracture healing could be monitored by X-ray radiograph of vertebrae. Vertebral radiograph could be the best method for assessing and monitoring the vertebral body fracture, especially for clinical use. PMID- 22040830 TI - [Calcium Pros and Cons--Which method is useful for diagnosis of vertebral body fracture; radiograph or MRI?--X-ray examination is not enough for diagnosis of fresh vertebral body fractures]. AB - The vertebral fractures of the elderly people are correctly diagnosed about 60% of the time if the X-ray is the only one used for diagnosis.The additional physical examination increases the rate dramatically, but it does not help locate the fracture.The follow-up X-ray examination increases the rate ; it becomes, however, too late to start an effective treatment. MRI is the best tool for the accurate diagnosis in the early stage. PMID- 22040831 TI - Health technology assessment: an evidence-based medicine perspective. AB - A challenge of health technology assessment is integrating the information from different disciplines. This talk focuses on the evidence-based medicine perspective and challenges 3 assumptions of health technology assessment: assumptions about effectiveness, assumptions about coverage by health technology assessment, and assumptions about costs being immutable. Challenging these assumptions has several implications. First is the need for better evidence on effects: both low-volume, high-cost technologies and low-cost, high-volume technologies that are ineffective drains on health care systems' resources. Second, cheap but effective technologies should be better promoted, as they can displace high-cost technologies. Finally, for effective but expensive technologies, we should work to lower the price and/or costs. PMID- 22040832 TI - Vulnerable patients' perceptions of health care quality and quality data. AB - BACKGROUND: Little is known about how patients served by safety-net hospitals utilize and respond to hospital quality data. OBJECTIVE: To understand how vulnerable, lower income patients make health care decisions and define quality of care and whether hospital quality data factor into such decisions and definitions. METHODS: Mixed quantitative and qualitative methods were used to gather primary data from patients at an urban, tertiary-care safety-net hospital. The study hospital is a member of the first public hospital system to voluntarily post hospital quality data online for public access. Patients were recruited from outpatient and inpatient clinics. Surveys were used to collect data on participants' sociodemographic characteristics, health literacy, health care experiences, and satisfaction variables. Focus groups were used to explore a representative sample of 24 patients' health care decision making and views of quality. Data from focus group transcripts were iteratively coded and analyzed by the authors. RESULTS: Focus group participants were similar to the broader diverse, low-income clinic. Participants reported exercising choice in making decisions about where to seek health care. Multiple sources influenced decision making processes including participants' own beliefs and values, social influences, and prior experiences. Hospital quality data were notably absent as a source of influence in health care decision making for this population largely because participants were unaware of its existence. Participants' views of hospital quality were influenced by the quality and efficiency of services provided (with an emphasis on the doctor-patient relationship) and patient centeredness. When presented with it, patients appreciated the hospital quality data and, with guidance, were interested in incorporating it into health care decision making. CONCLUSIONS: Results suggest directions for optimizing the presentation, content, and availability of hospital quality data. Future research will explore how similar populations form and make choices based on presentation of hospital quality data. PMID- 22040833 TI - Ultrastaging for micrometastases in para-aortic lymph nodes in patients with carcinoma of the uterine cervix. PMID- 22040834 TI - Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta analysis. AB - OBJECTIVE: The presence of T cells within the epithelial component of tumors, as histologic evidence of anti-tumor immunity, has been associated with a survival advantage in multiple studies across diverse patient cohorts. We performed a meta analysis of studies evaluating the prognostic value of tumor-infiltrating lymphocytes (TIL) on survival among women with ovarian cancer and to investigate factors associated with variations in this effect, including patient characteristics, surgical outcomes, tumor histology, and study protocols. METHOD: Published studies that evaluated the association between TIL and patient survival were identified. Descriptive statistics, outcome data, and study quality were extracted from studies that met inclusion criteria. Hazard ratios and 95% confidence intervals were pooled across studies using the random-effects model. Publication bias was investigated using a funnel plot and heterogeneity was assessed with subgroup analysis and I(2) statistics. RESULTS: Ten suitable studies comprising 1815 patients with ovarian cancer were analyzed. Our results demonstrate that a lack of intraepithelial TILs is significantly associated with a worse survival among patients (pooled HR: 2.24, 95% CI; 1.71-2.91). Variations in the prognostic value of TIL status based on debulking status, scoring method, and geographic regions were identified. CONCLUSIONS: Intraepithelial TILs are a robust predictor of outcome in ovarian cancer and define a specific class of patients, whose distinct tumor biology should be taken into account in devising appropriate therapeutic strategies. PMID- 22040835 TI - Functional interaction between peritoneal mesothelial cells and stem cells of ovarian yolk sac tumor (SC-OYST) in peritoneal dissemination. AB - OBJECTIVE: In recent years it has been indicated that ecological niches play important roles in the maintenance of cancer stem cells (CSCs). We investigated interactions between peritoneal mesothelial cells and SC-OYST based on the hypothesis that peritoneal mesothelial cells have the potential to provide one of the niches for SC-OYST. METHODS: We divided NOY1 cells into CD133-positive and negative cells. Using the co-culture of NOY1 and peritoneal mesothelial cells, we compared the expression of CD133, colony formation, and the capacity for migration and invasion. In addition, we assessed the inhibitory effects of AMD3100, a neutralizing antibody against a chemokine receptor (CXCR4). Then, we examined whether AMD3100 affects the tumorigenicity of NOY1-CD133+ cells in vivo. RESULTS: When NOY1 cells were co-cultured with peritoneal mesothelial cells, we observed the high-level expression of CD133. The number of colonies of NOY1 CD133+ cells was 2.4 times that of NOY1-CD133- cells. In contrast, on co-culture with peritoneal mesothelial cells, it was 4.3 times. When NOY1 cells were cultivated in the upper layer and peritoneal mesothelial cells were cultivated in the lower chamber, NOY1-CD133+ cells showed a greater capacity for migration and invasion than NOY1-CD133- cells. By adding AMD3100 to the co-culture systems, the colony formation, migration, and invasion of NOY1-CD133+ cells were inhibited. In addition, AMD3100 inhibited the tumorigenicity of NOY1-CD133+ cells in vivo. CONCLUSIONS: Our data suggest that peritoneal mesothelial cells have the potential to provide one of the niches for NOY1 cells. Investigation of the niches of SC-OYST will help elucidate important targets for therapeutic approaches. PMID- 22040836 TI - The more things change the more they stay the same. PMID- 22040837 TI - Differential effects of stimulus characteristics during knee joint perturbation on hamstring and quadriceps reflex responses. AB - When stretching muscles of the ankle joint, stretch velocity and amplitude were shown to selectively influence specific parts of the stretch reflex. The present study investigated whether similar effects can be observed at the knee joint. Seventeen subjects were exposed to sudden anterior tibial translations. The influence of stimulus amplitude was analyzed by applying a low (LIMP) or high impulse (HIMP). To investigate the influence of velocity, rate of force development of the perturbation was chosen either low (LRFD) or high (HRFD). Activation of biceps femoris (BF), semitendinosus (ST), vastus medialis (VM) and vastus lateralis (VL) was calculated in four consecutive timeframes (P0, P1, P2, P3). During P1, RFD (ST: p<.05; BF: p<.01; VM: p<.05; VL: p>.05) and during P2, impulse (ST: p<.05; BF: p<.01; VM: p<.01; VL: p<.01) did significantly influence reflex activation. The present study showed that stimulus characteristics influenced specific reflex components of knee joint muscles. As only hamstring muscles were stretched, whereas quadriceps was unloaded, it is concluded that different mechanisms like homonymous and heteronymous muscle afferents as well as joint and skin afferents might contribute to the reflex responses. PMID- 22040838 TI - Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. AB - OBJECTIVE: Physical activity or metformin enhances insulin sensitivity and opposes the progression from prediabetes to type 2 diabetes. The combination may be more effective because each treatment stimulates AMP-activated protein kinase activity in skeletal muscle. We evaluated the effects of exercise training plus metformin on insulin sensitivity in men and women with prediabetes, compared with each treatment alone. RESEARCH DESIGN AND METHODS: For 12 weeks, men and women with prediabetes were assigned to the following groups: placebo (P), 2,000 mg/day metformin (M), exercise training with placebo (EP), or exercise training with metformin (EM) (n = 8 per group). Before and after the intervention, insulin sensitivity was measured by euglycemic hyperinsulinemic (80 mU/m(2)/min) clamp enriched with [6,6-(2)H]glucose. Changes due to intervention were compared across groups by repeated-measures ANOVA. RESULTS: All three interventions increased insulin sensitivity (P < 0.05) relative to the control group. The mean rise was 25-30% higher after EP than after either EM or M, but this difference was not significant. CONCLUSIONS: Insulin sensitivity was considerably higher after 12 weeks of exercise training and/or metformin in men and women with prediabetes. Subtle differences among condition means suggest that adding metformin blunted the full effect of exercise training. PMID- 22040839 TI - Vitamin D levels and asymptomatic coronary artery disease in type 2 diabetic patients with elevated urinary albumin excretion rate. AB - OBJECTIVE: Coronary artery disease (CAD) is the major cause of morbidity and mortality in type 2 diabetic patients. Severe vitamin D deficiency has been shown to predict cardiovascular mortality in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We investigated the association among severe vitamin D deficiency, coronary calcium score (CCS), and asymptomatic CAD in type 2 diabetic patients with elevated urinary albumin excretion rate (UAER) >30 mg/24 h. This was a cross sectional study including 200 type 2 diabetic patients without a history of CAD. Severe vitamin D deficiency was defined as plasma 25-hydroxyvitamin D (p 25[OH]D3) <12.5 nmol/L. Patients with plasma N-terminal pro-brain natriuretic peptide >45.2 ng/L or CCS >=400 were stratified as being high risk for CAD (n= 133). High-risk patients were examined by myocardial perfusion imaging (MPI; n = 109), computed tomography angiography (n = 20), or coronary angiography (CAG; n = 86). Patients' p-25(OH)D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry. RESULTS: The median (range) vitamin D level was 36.9 (3.8-118.6) nmol/L. The prevalence of severe vitamin D deficiency was 9.5% (19/200). MPI or CAG demonstrated significant CAD in 70 patients (35%). The prevalence of CCS >=400 was 34% (68/200). Severe vitamin D deficiency was associated with CCS >=400 (odds ratio [OR] 4.3, 95% CI [1.5-12.1], P = 0.005). This association persisted after adjusting for risk factors (4.6, 1.5-13.9, P = 0.007). Furthermore, severe vitamin D deficiency was associated with asymptomatic CAD (adjusted OR 2.9, 1.02-7.66, P = 0.047). CONCLUSIONS: In high-risk type 2 diabetic patients with elevated UAER, low levels of vitamin D are associated with asymptomatic CAD. PMID- 22040840 TI - Short-term exenatide treatment leads to significant weight loss in a subset of obese women without diabetes. AB - OBJECTIVE: To investigate the effect of treatment with the glucagon-like peptide 1 receptor agonist exenatide on weight loss and metabolic parameters in obese nondiabetic women. RESEARCH DESIGN AND METHODS: Forty-one obese women (aged 48 +/ 11 years and BMI 33.1 +/- 4.1 kg/m(2)) participated in a 35-week randomized, double-blind, placebo-controlled, crossover study, including two 16-week treatment periods separated by a 3-week washout period. There was no lifestyle intervention. The primary outcome was change in body weight. RESULTS: Subjects treated with exenatide lost an average of 2.49 +/- 0.66 kg compared with a 0.43 +/- 0.63 kg weight gain during placebo treatment. Weight loss with exenatide treatment was noted at 2 weeks. The degree of weight loss could be stratified. A total of 30% of subjects were high responders who lost >=5% body weight (-7.96 +/ 0.52%), 39% were moderate responders who lost <5% body weight (-2.43 +/- 0.45%), and 31% were nonresponders who gained weight (1.93 +/- 0.53%). Waist circumference also decreased significantly with exenatide treatment. Subjects experienced more nausea during exenatide treatment compared with placebo, but the severity decreased over time and did not correlate with weight loss. CONCLUSIONS: Short-term exenatide treatment was associated with modest weight loss and decreased waist circumference in a cohort of obese nondiabetic women. A subset of individuals demonstrated robust weight loss that was detected very early in the course of treatment. PMID- 22040841 TI - Hepatic and peripheral insulin sensitivity and diabetes remission at 1 month after Roux-en-Y gastric bypass surgery in patients randomized to omentectomy. AB - OBJECTIVE: Early after Roux-en-Y gastric bypass (RYGB), there is improvement in type 2 diabetes, which is characterized by insulin resistance. We determined the acute effects of RYGB, with and without omentectomy, on hepatic and peripheral insulin sensitivity. We also investigated whether preoperative diabetes or postoperative diabetes remission influenced tissue-specific insulin sensitivity after RYGB. RESEARCH DESIGN AND METHODS: We studied 40 obese (BMI 48 +/- 8 kg/m(2)) participants, 17 with diabetes. Participants were randomized to RYGB alone or in conjunction with omentectomy. Hyperinsulinemic-euglycemic clamps with isotopic-tracer infusion were completed at baseline and at 1 month postoperatively to assess insulin sensitivity. RESULTS: Participants lost 11 +/- 4% of body weight at 1 month after RYGB, without an improvement in peripheral insulin sensitivity; these outcomes were not affected by omentectomy, preoperative diabetes, or remission of diabetes. Hepatic glucose production (HGP) and the hepatic insulin sensitivity index improved in all subjects, irrespective of omentectomy (P <= 0.001). Participants with diabetes had higher baseline HGP values (P = 0.003) that improved to a greater extent after RYGB (P = 0.006). Of the 17 participants with diabetes, 10 (59%) had remission at 1 month. Diabetes remission had a group * time effect (P = 0.041) on HGP; those with diabetes remission had lower preoperative and postoperative HGP. CONCLUSIONS: Peripheral insulin sensitivity did not improve 1 month after RYGB, irrespective of omentectomy, diabetes, or diabetes remission. Hepatic insulin sensitivity improved at 1 month after RYGB and was more pronounced in patients with diabetes. Improvement in HGP may influence diabetes remission early after RYGB. PMID- 22040842 TI - Usefulness of the high triglyceride-to-HDL cholesterol ratio to identify cardiometabolic risk factors and preclinical signs of organ damage in outpatient children. AB - OBJECTIVE: To evaluate whether the high triglyceride-to-HDL cholesterol (TG-to HDL-C) ratio is associated with cardiometabolic risk (CMR) factors and preclinical signs of organ damage in an outpatient population of white children and adolescents. RESEARCH DESIGN AND METHODS: The study population included 884 subjects (aged 6-16 years), of whom 206 (23%) were normal weight, 135 (15%) were overweight, and 543 (61%) were obese. Biochemical variables were analyzed in the whole sample, whereas homocysteine and left ventricular (LV) geometry and function were evaluated in 536 and 258 children, respectively. RESULTS: The percentage of pubertal children (P < 0.001), as well as measurements of BMI, waist circumference, homeostasis model assessment of insulin resistance, white blood cell count, alanine aminotransferase (ALT), systolic blood pressure (P < 0.0001, for all), creatinine (P < 0.001), and diastolic blood pressure (P < 0.02), increased from the lowest to the highest tertile of the TG-to-HDL-C ratio. Age, sex, homocysteine, and glomerular filtration rate did not change. Moreover, interventricular septum thickness, relative wall thickness, and LV mass index (P = 0.01 to P < 0.0001) increased across tertiles of the TG-to-HDL-C ratio. Children with a TG-to-HDL-C ratio >=2.0 showed a two- to threefold higher risk of elevated ALT levels and concentric LV hypertrophy than those with a TG-to-HDL-C ratio <2.0, independent of confounding factors. CONCLUSIONS: The high TG-to-HDL-C ratio is associated with several CMR factors and preclinical signs of liver and cardiac abnormalities in the outpatient, white pediatric population. Thus, a TG to-HDL-C ratio >=2.0 may be useful in clinical practice to detect children with a worsened CMR profile who need monitoring to prevent cardiovascular disease in adulthood. PMID- 22040843 TI - Outcomes of allogeneic hematopoietic cell transplantation for adolescent and young adults compared with children and older adults with acute myeloid leukemia. AB - Adolescents and young adults (AYAs) with cancer have not experienced improvements in survival to the same extent as children and older adults. We compared outcomes among children (<15 years), AYAs (15-40 years) and older adults (>40 years) receiving allogeneic hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML). Our cohort consisted of 900 children, 2,708 AYA, and 2,728 older adult recipients of HLA-identical sibling or unrelated donor (URD) transplantation using myeloablative or reduced-intensity/nonmyeloablative conditioning. Outcomes were assessed over three time periods (1980-1988, 1989 1997, 1998-2005) for siblings and two time periods (1989-1997, 1998-2005) for URD HCT. Analyses were stratified by donor type. Results showed overall survival for AYAs using either siblings or URD improved over time. Although children had better and older adults had worse survival compared with AYAs, improvements in survival for AYAs did not lag behind those for children and older adults. After sibling donor HCT, 5-year adjusted survival for the three time periods was 40%, 48%, and 53% for children, 35%, 41%, and 42% for AYAs, and 22%, 30%, and 34% for older adults. Among URD HCT recipients, 5-year adjusted survival for the two time periods was 38% and 37% for children, 24% and 28% for AYAs, and 19% and 23% for older adults. Improvements in survival occurred because of a reduction in risk of treatment-related mortality. The risk of relapse did not change over time. Improvements in survival among AYAs undergoing allogeneic HCT for AML have paralleled those among children and older adults. PMID- 22040844 TI - Risk factors for 30-day hospital readmission following myeloablative allogeneic hematopoietic cell transplantation (allo-HCT). AB - Patient readmission within 30 days from discharge has been perceived by the Centers for Medicare and Medical Services as an indicator of poor healthcare quality for specific high-cost medical conditions. Patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are often being readmitted. Our study identified the risk factors for 30-day readmission among 618 adult recipients of myeloablative allo-HCT from 1990 to 2009. Two hundred forty-two (39%) of 618 patients (median age = 42 years [range: 18-66]) were readmitted a median of 10 days (range: 1-30) from their hospital discharge. Median duration of readmission was 8 days (range: 0-103). Infections (n = 68), fever with or without identified source of infection (n = 63), gastrointestinal complications (n = 44), graft-versus-host disease (GVHD) (n = 38), and other reasons (n = 29) accounted for 28%, 26%, 18%, 16%, and 12% of readmissions, respectively. During their index admission, patients who were subsequently readmitted had more documented infections (P < .001), higher hematopoietic cell transplantation comorbidity index (HCT-CI) (P < .01), total body irridiation (TBI)-based conditioning (P < .001), unrelated donor (P < .001), and peripheral stem cell (P = .014) transplantation. In multivariable analysis, HCT-CI (odds ratio [OR] = 1.78; 95% confidence interval [CI], 1.25-2.52), TBI-based preparative regimen (OR = 2.63; 95% CI, 1.67-4.13), and infection during admission for allo-HSCT (OR = 2.00; 95% CI, 1.37-2.92) predicted 30-day readmission. Thirty-day readmission itself was an independent predictor of all cause mortality (hazard ratio [HR](Adj) = 1.66; 95% CI, 1.36-2.10). Our data emphasize the importance of a risk-standardized approach to 30-day hospital readmission if it is used as a quality-of-care metric for bone marrow transplantation. PMID- 22040845 TI - Psychosis after epilepsy surgery: report of three cases. AB - Temporal lobe epilepsy surgery has become a successful alternative in patients with refractory epilepsy. However, the outcome of epilepsy surgery may be affected by the occurrence of postsurgical psychiatric symptoms, such as psychosis. This report describes three cases of refractory temporal lobe epilepsy and hippocampal sclerosis, which, after anterior temporal lobectomy, presented with acute psychosis. One of them had a history of acute psychosis, and all of them met criteria for Cluster A personality disorder (schizoid/schizotypal) during psychiatric assessment prior to surgery. The three cases had a good seizure outcome (Engel I), but, on follow-up during the first year after surgery, developed an acute psychotic episode compatible with schizoaffective disorder; brief psychotic disorder; and a delusional disorder, respectively, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Treatment with low-dose risperidone was successful. PMID- 22040846 TI - Monoclonal antibodies against dengue NS2B and NS3 proteins for the study of protein interactions in the flaviviral replication complex. AB - The replication of dengue virus (DENV) RNA requires at least two viral non structural (NS) proteins, NS3 and NS5. To facilitate the study of the DENV replication complex, human monoclonal IgG that are specific for NS proteins have been generated and characterised. The anti-NS3 IgG, 3F8, binds a conserved epitope (aa526-531) in the NS3 helicase domain, and cross-reacts with NS3 from all four DENV serotypes and the related yellow fever virus. The anti-NS2B IgG, 3F10, binds aa49-66 of NS2B (CF18), which forms part of the 47 aa hydrophilic cofactor region required for NS3 protease activity. The specificity of the IgG for their respective non-structural proteins has been demonstrated by immunofluorescence of cells infected with DENV and Western blotting. 3F8 is able to co-immunoprecipitate NS3 and NS5 from BHK-21 cells infected with DENV2, and 3F10 is able to detect an interaction between recombinant NS2B(CF18)NS3 full length protein and the NS5 RNA-dependent RNA polymerase (RdRp) domain in an ELISA based binding assay. The assay is specific and highly reproducible, with a clear binding curve seen when RdRp is incubated with increasing amounts of full-length NS3, but not the NS3 protease domain. The NS3 helicase domain competes with NS3 full-length for NS5 RdRp binding, with a K(d.) of 2.5MUM. Since NS3 and NS5 are required for DENV replication, this fascile assay could be used to screen for non nucleoside, allosteric inhibitors that disrupt the interaction between the two proteins. PMID- 22040847 TI - A hybrid-capture assay to detect HPV mRNA ratios in cervical specimens. AB - Human papillomavirus (HPV) DNA screening benefits cervical cancer diagnosis, but a few HPV infections result in cancer. Assays that predict cancer are desirable. A potential biomarker is the ratio of HPV E6-7 over E2 transcripts, which may increase during early cancer progression. Modified hybrid-capture technology detected, in separate wells, HPV E6-7 or E2 mRNA of HPV 16 or HPV 18 in samples. The limit of detection was approximately 1000 copies of in vitro transcribed RNA with linear dynamic range approximately four logs. No cross-reactivity between HPV 16 and HPV 18 mRNAs was detected. RNA of SiHa cells was stable in clinical specimen pools for 67 days, as determined by RT-PCR. The ratio of HPV E6-7:E2 mRNAs was relatively high for cancer cells lines, SiHa, Caski and HeLa cells preserved in clinical specimen pools. A broad distribution of HPV 16 E6-7:E2 mRNA ratio was detected in a small set of clinical specimens with various histological diagnoses. Some specimen ratios were so high for cancer cell lines, but the significance of the results needs to be determined. This method may help determine the pattern of gene expression in HPV-related disease or in other systems. PMID- 22040848 TI - Getting the signal to noise ratio right in the management of diabetes in primary care: time to stratify risk and focus on outcomes rather than process. PMID- 22040849 TI - A bibliometric analysis of Australian general practice publications from 1980 to 2007 using PubMed. AB - BACKGROUND: We analysed Australian general practice (GP) publications in PubMed from 1980 to 2007 to determine journals, authors, publication types, national health priority areas (NHPA) and compared the results with those from three specialties (public health, cardiology and medical informatics) and two countries (the UK and New Zealand). METHOD: Australian GP publications were downloaded in MEDLINE format using PubMed queries and were written to a Microsoft Access database using a software application. Search Query Language and online PubMed queries were used for further analysis. RESULTS: There were 4777 publications from 1980 to 2007. Australian Family Physician (38.1%) and the Medical Journal of Australia (17.6%) contributed 55.7% of publications. Reviews (12.7%), letters (6.6%), clinical trials (6.5%) and systematic reviews (5%) were the main PubMed publication types. Thirty five percent of publications addressed National Health Priority Areas with material on mental health (13.7%), neoplasms (6.5%) and cardiovascular conditions (5.9%). The comparable numbers of publications for the three specialties were: public health - 80 911, cardiology - 15 130 and medical informatics - 3338; total country GP comparisons were: UK - 14 658 and New Zealand - 1111. DISCUSSION: Australian GP publications have shown an impressive growth from 1980 to 2007 with a 15-fold increase. This increase may be due in part to the actions of the Australian government over the past decade to financially support research in primary care, as well as the maturing of academic general practice. This analysis can assist governments, researchers, policy makers and others to target resources so that further developments can be encouraged, supported and monitored. PMID- 22040850 TI - Presentation of body mass index within an electronic health record to improve weight assessment and counselling in children and adolescents. AB - BACKGROUND: Assessment of weight and counselling on nutrition and physical activity is infrequently conducted during well child visits, despite recent expert recommendations. OBJECTIVE: We investigated whether automatic calculation of body mass index (BMI) in an electronic health record improved assessment of weight and counselling on nutrition and physical activity. METHODS: Retrospective review of well child visit records of children between two and 18 years of age (n =550) before and after implementation of an electronic health record system at an academic medical centre's paediatric clinic. Body mass index was automatically calculated and presented within the electronic health record. We measured clinicians' documentation of assessment of weight status, and assessment of and counselling for nutrition and physical activity risk factors. RESULTS: Documentation of assessment of BMI and weight status did not increase. There were no consistent increases in assessment for or counselling on specific nutrition and physical activity behaviours, except with respect to high calorie food intake. Although overall assessment of physical activity decreased, physical activity counselling significantly increased. Documentation of the presence of high-risk family history increased significantly; the provision of counselling for high-risk family history did not show any corresponding increase. Patients with higher BMI percentile scores were more completely assessed for weight status. Completeness of weight status assessment was associated with increased counselling for nutrition and physical activity. CONCLUSIONS: Passive changes, such as automatic calculation of BMI, are insufficient to result in systematic improvements in assessment of weight and counselling for nutrition and physical activity. PMID- 22040851 TI - Adoption and use of health information technology in physician practice organisations: systematic review. AB - BACKGROUND: Health information technology (HIT) has the potential to improve clinical outcomes, increase health provider productivity and reduce healthcare costs. Over half of all patient care is delivered in physician practice organisations, yet adoption and utilisation of HIT in these groups lags behind inpatient facilities. OBJECTIVE: To better understand current utilisation rates along with benefits and barriers to HIT adoption in physician practice organisations. METHODS: Published literature on the adoption and use of HIT in physician practice organisations within the USA between 12 January 2004 and 12 January 2009 and indexed in MEDLINE and EMBASE was included in the systematic review. Grey literature was also searched. Studies related to the adoption and use of HIT in hospitals and community health centres were excluded. RESULTS: A total of 119 articles were eligible for inclusion in the review. Adoption rates across physician groups remain low, with between 9% and 29% of practices having implemented electronic medical records. HIT improves clinical outcomes, increases the use of vaccinations and improves medication adherence. Furthermore, HIT adoption leads to cost savings for physician groups, improves staff productivity and enriches patient-provider interactions. The largest barrier to HIT adoption in physician groups is the high initial and ongoing costs of electronic systems. Lack of sufficient training, a disorganised or non-receptive practice culture and technological problems such as inadequate connectivity appear to impede effective HIT use. CONCLUSIONS: HIT has the potential to positively impact on physician practice organisations, although significant and diverse barriers block adoption. Research into these obstacles should be coupled with efforts to understand barriers to effective implementation after HIT adoption. PMID- 22040852 TI - General practitioners' and nurses' experiences of using computerised decision support in screening for diabetic foot disease: implementing Scottish Clinical Information - Diabetes Care in routine clinical practice. AB - OBJECTIVE: The Scottish Care Information - Diabetes Collaboration (SCI-DC) developed a computer-based information system to create a shared electronic record for use by all involved in the care of patients with diabetes mellitus. The objectives of this study were to understand primary care practitioners' views towards screening for diabetic foot disease and their experience of the SCI-DC system. METHOD: We conducted an exploratory study using qualitative methods. Semi structured interviews were audiotape-recorded, transcribed and subjected to thematic analysis. Seven practice nurses and six general practitioners (GPs) with special responsibility for diabetes care in NHS Lothian participated. RESULTS: Primary care clinicians reported good systems in place to screen for diabetes related complications and to refer their patients to specialist care. Foot ulceration was rarely observed; other diabetes related conditions were seen as a higher priority. Most had heard of the SCI-DC foot assessment tool, but its failure to integrate with other primary care information technology (IT) systems meant it was not used in these general practices. CONCLUSIONS: Adoption of the SCI-DC foot assessment tool in primary care is not perceived as clinically necessary. Although information recorded by specialist services on SCI-DC is helpful, important structural barriers to its implementation mean the potential benefits associated with its use are unlikely to be realised; greater engagement with primary care priorities for diabetes management is needed to assist its successful implementation and adoption. PMID- 22040853 TI - Implementing an integrated computerised information system about foot problems in diabetes is not enough to ensure adoption. Commentary on: general practitioners' and nurses' experiences of using computerised decision support in screening for diabetic foot disease: implementing Scottish Clinical Information - Diabetes Care in routine clinical practice. PMID- 22040854 TI - Using routine data to conduct small area health needs assessment through observing trends in demographics, recording of common mental health problems (CMHPs) and sickness certificates: longitudinal analysis of a northern and London locality. AB - BACKGROUND: Many practices in the UK have computerised information dating back to the 1990s. These health records provide contemporaneous collected longitudinal data for analysis of health trends and their management in primary care over time. OBJECTIVE: This study examines the trends in common mental health problems (CMHPs), prescription of antidepressant, anxiolytics and hypnotics and medical certificates over four years to highlight the strengths and pitfalls in trends analysis using primary care data. METHOD: Relevant clinical information for the first six months of each of the calendar years 2004, 2005, 2006 and 2007 were extracted from participating practices in a London locality and in the North. RESULTS: Between 2004 and 2007 recorded episodes of CMHPs rose from 33 to 45 per thousand adults in the northern site, and from 19 to 22 in the London site. Prescriptions of antidepressants, anxiolytics and hypnotics rose (from 381.4 to 418 per thousand adults) in the northern site but did not increase in the London site. Medical certificates increased steadily (from 32.7 to 61.6 per thousand adults with a CMHP) in the London site but not in the northern. Recorded episodes of CMHPs and prescriptions of antidepressants, anxiolytics or hypnotics are much higher in the northern site than the London site; the rate of medical certificates per thousand adults with CMHPs in the northern site is more than ten times that in the London site. CONCLUSIONS: Demographics, diagnostic and prescribing data are of high quality in primary care, and they could be used more to understand local health needs and inform commissioning decisions. PMID- 22040855 TI - Creating a diabetes foot reminder-based registry using the electronic medical record. AB - OBJECTIVE: We created a new diabetes foot examination clinical reminder to directly populate a foot risk registry and examined its accuracy versus administrative data. METHODS: A pre- and post-test design assessed accuracy of coding foot risk and clinician acceptability. The intervention hospital's reminder was replaced with a dialogue tick box containing the International Diabetic Foot Classification System to populate risk using health factors. RESULTS: There were no hospital agreement differences for each foot condition except diabetes and peripheral neuropathy, demonstrating higher agreement at the intervention hospital. There were no differences in service agreement adherence or consulting rates although both demonstrated significantly lower consulting rates at study end. The intervention hospital had a significantly lower patient cancellation rate (1% v. 5%, P=0.01) and better coding for grade 3 patients. The new reminder demonstrated high acceptability. CONCLUSIONS: The registry system resulted in improved discrimination of the highest foot risk. Further testing is recommended. PMID- 22040856 TI - Commentary on: creating a diabetes foot reminder-based registry using the electronic medical record. PMID- 22040857 TI - [Therapeutic patient education in heart failure: a program's assessment]. AB - Heart failure is a chronic, common and severe disease. It leads to frequent hospitalizations and decrease of patient's quality of life. A therapeutic patient education program, named "school of heart failure" was implemented at Antoine Beclere hospital. AIM OF THE STUDY: To assess the effectiveness of this program. PATIENTS AND METHODS: This therapeutic patient education program included patients with heart failure, hospitalized in a cardiology unit. Four types of evaluation were carried out: evaluation of patients' skills before they leave the hospital, patient's knowledge (associated with the degree of certainty), satisfaction regarding the program and self-assessment of changes in their lifestyle 3 months after discharge. RESULTS: Twenty-four patients were included in 9 months. The program's evaluation showed promising results with respect to the acquisition of skills (94%), the improvement of patients' knowledge associated with self-confidence increase, their satisfaction towards the program (80%) and their ability to change their habits (75%). Self-assessment has demonstrated changes in their lifestyle. CONCLUSION: These preliminary results are promising according to the program's effectiveness and its ability to meet patients' educational needs. The program was certified by French authorities in 2011. Knowledge and skills acquisition will have to be confirmed on long term. PMID- 22040858 TI - [Renal artery denervation for treating refractory hypertension]. AB - Arterial hypertension is a major healthcare issue affecting between 30 and 40% of the adult population in industrialized countries. Despite the availability of numerous pharmaceutical treatments, arterial hypertension often remains uncontrolled. A non-negligible percentage of patients are refractory to multiple drug therapy, which exposes them to an increased risk of cardiovascular events. Percutaneous, renal denervation using a catheter connected to a low energy radiofrequency generator has proven effective in decreasing arterial pressure in patients resistant to medical therapy, by reducing afferent nerve activity. In order to be eligible for this therapeutic approach, patients must have uncontrolled essential hypertension despite treatment with a combination of three anti-hypertensive drugs including a diuretic agent, and >= 45mL/min glomerular filtration rate. The initial registry study demonstrated that catheter-based sympathetic renal denervation was a simple and safe procedure resulting in a significant and durable reduction in arterial pressure. Subsequently, a randomized controlled trial (the Symplicity HTN-2 trial) showed a mean 32/12 mmHg decrease in blood pressure measurements in the group of patients who underwent renal denervation whereas no difference was observed in the control group. The reduction in blood pressure was still present at 24-month follow-up. No procedure related complications were reported and no instances of renal artery stenosis or aneurysmal dilatation were evidenced during the follow-up period. No cases of renal function impairment or deterioration were recorded. This technique seems to be a promising strategy in patients suffering from this serious condition. In order to demonstrate the actual benefit of this technique, we report the case of two patients who underwent renal denervation in our institution. PMID- 22040859 TI - Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment. AB - Reduction of cerebral blood flow is an important risk factor for dementia states and other brain dysfunctions. In present study, the effects of permanent occlusion of common carotid arteries (2VO), a well established experimental model of brain ischemia, on memory function were investigated, as assessed by reference and working spatial memory protocols and the object recognition task; cell damage to the hippocampus, as measured through changes in immunoreactivity for GFAP and the neuronal marker NeuN was also studied. The working hypothesis is that metabolic impairment following hypoperfusion will affect neuron and glial function and result in functional damage. Adult male Wistar rats were submitted to the modified 2VO method, with the right common carotid artery being occluded first and the left one week later, and tested seven days, three and six months after the ischemic event. A significant cognitive deficit was found in both reference and working spatial memory, as well as in the object recognition task, three and six months after surgery. Neuronal death and reactive astrogliosis were already present at 7 days and continued for up to 3 months after the occlusion; interestingly, there was no significant reduction in hippocampal volume. Present data suggests that cognitive impairment caused by brain hypoperfusion is long - lasting and persists beyond the time point of recovery from glial activation and neuronal loss. PMID- 22040860 TI - Acute and chronic methylphenidate modulates the neuronal activity of the caudate nucleus recorded from freely behaving rats. AB - Methylphenidate (MPD) is currently one of the most prescribed drug therapies for attention deficit/hyperactivity disorder (ADHD) and moreover is abused for cognitive enhancement and used for recreation by the young and adults. Methylphenidate is used for prolonged periods of time and its mechanism of action on the brain is still unknown. The main action of MPD is known to act on the motive circuit of the brain, and one of these structures is the caudate nucleus (CN). The objective of this study was to investigate the neurophysiological properties of the CN neurons in response to acute and chronic administration of MPD in freely behaving animals, previously implanted with permanent semi microelectrodes. Twenty-six rats were permanently implanted with semi microelectrodes into the CN using general anesthesia. On experimental day one (ED1) the rat was placed into the testing chamber, and neuronal activity was recorded using a wireless (telemetric) headstage device following both a saline and a 2.5 mg/kg MPD injection. From ED2 to ED6 daily injections of 2.5 mg/kg MPD were administered without recordings to induce a chronic effect of the drug, preceded by three days of washout (ED7-ED9) where no injections were given. On ED10 rats were placed back into the testing chamber, the wireless headstage device was attached to skull cap and recordings were resumed for 1 h each following both a saline and re-challenge administration of 2.5 mg/kg MPD. Sixty seven CN neuronal recorded units from twenty-six animals with identical shape and amplitude at ED1 and ED10 were evaluated. All the 67 CN units responded to MPD administration, 70% (47/67) CN units exhibited an increase in activity following initial 2.5 mg/kg MPD administration and 30% (20/67) exhibited a decrease in neuronal activity. On ED10 all the CN units showed a significant change in their firing rate baseline compared to ED1 baseline, 52% (35/67) exhibiting an increase in their ED10 baseline activity compared to ED1 baseline activity and 48% (32/67) of the CN units at ED10 exhibited decreasing activity. All the CN units responded significantly to MPD rechallenge at ED10, 57% (38/67) of the units exhibited increased neuronal activity while 43% (29/67) exhibited decreasing neuronal activity. The results indicate that the majority of the CN units exhibited neurophysiological sensitization. PMID- 22040861 TI - Reproducibility of sodium MRI measures of articular cartilage of the knee in osteoarthritis. AB - OBJECTIVE: To determine the stability and reproducibility of the sodium magnetic resonance imaging (MRI) signal measured in the articular cartilage of the knee in both healthy volunteers and osteoarthritis (OA) patients. DESIGN: This was a prospective Research Ethics Committee approved study that acquired sodium and proton MRI data from 15 subjects with OA (three males, age 64 +/- 10) and five healthy controls age and sex matched over the group. Each subject underwent standing planar radiographs of their knees for radiological scoring as well as symptomatological assessment questionnaires. In two MRI sessions on the same day, high resolution double-echo steady state (DESS) and 3D short echo time sodium MRI images of the most diseased knee were acquired and co-registered in each session. A blinded reader (LT) manually delineated the articular cartilage into four discrete regions, and two combined regions, on the DESS images. These regions were applied to the sodium images, and a median sodium signal from each reported. Within-subject and between-subject coefficients of variation were estimated and intraclass correlation coefficients for the healthy control group, OA subject group, and all pooled subjects group were calculated. RESULTS: Within-subject variability of sodium MRI at 3T was 3.2% overall, and 2.0% in healthy age-matched volunteers compared to a reproducibility of 3.6% on OA subjects. CONCLUSIONS: The reproducibility of sodium MRI was similar in both healthy controls and OA subjects. Researchers piloting techniques in healthy controls thus may expect a similar reproducibility in a controlled trial involving subjects with American College of Rheumatology (ACR)-defined OA of the knee. PMID- 22040862 TI - TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya. AB - BACKGROUND: Squamous Cell Carcinoma of Esophagus is one of the most common malignancies in both men and women in eastern and south-eastern Africa. In Kenya, clinical observations suggest that this cancer is frequent in the Rift Valley area. However, so far, there has been no report on the molecular characteristics of esophageal squamous cell carcinoma (ESCC) in this area. RESULTS: We have analyzed TP53 mutations, the presence of human papilloma virus (HPV) DNA and expression of inflammation markers Cyclooxygenase 2 (Cox-2) and Nitrotyrosine (NTyR) in 28 cases (13 males and 15 females) of archived ESCC tissues collected at the Moi Teaching and Referral Hospital in Eldoret, Kenya. Eleven mutations were detected in TP53 exons 5 to 8 (39%). All ESCC samples were negative for HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82. Immunohistochemical analysis of Cox-2 and NTyR showed a low proportion of positive cases (17.4% and 39.1%, respectively). No association between the above markers and suspected risk factors (alcohol or tobacco use, hot tea drinking, use of charcoal for cooking) was found. CONCLUSION: Our findings suggest that mechanisms of esophageal carcinogenesis in eastern Africa might be different from other parts of the world. Low prevalence of TP53 mutation compared with other intermediate or high incidence areas of the world highlights this hypothesis. Our data did not support a possible ole of HPV in this series of cases. Further studies are needed to assess and compare the molecular patterns of ESCC from Kenya with those of high-incidence areas such as China or Central Asia. PMID- 22040863 TI - Advancing obstetric and neonatal care in a regional hospital in Ghana via continuous quality improvement. AB - OBJECTIVE: To reduce maternal and neonatal death at a large regional hospital through the use of quality improvement methodologies. METHODS: In 2007, Kybele and the Ghana Health Service formed a partnership to analyze systems and patient care processes at a regional hospital in Accra, Ghana. A model encompassing continuous assessment, implementation, advocacy, outputs, and outcomes was designed. Key areas for improvement were grouped into "bundles" based on personnel, systems management, and service quality. Primary outcomes included maternal and perinatal mortality, and case fatality rates for hemorrhage and hypertensive disorders. Implementation and outcomes were evaluated tri-annually between 2007 and 2009. RESULTS: During the study period, there was a 34% decrease in maternal mortality despite a 36% increase in patient admission. Case fatality rates for pre-eclampsia and hemorrhage decreased from 3.1% to 1.1% (P<0.05) and from 14.8% to 1.9% (P<0.001), respectively. Stillbirths were reduced by 36% (P<0.05). Overall, the maternal mortality ratio decreased from 496 per 100000 live births in 2007 to 328 per 100,000 in 2009. CONCLUSION: Maternal and newborn mortality were reduced in a low-resource setting when appropriate models for continuous quality improvement were developed and employed. PMID- 22040864 TI - [Postoperative diaphragmatic paralysis after kidney transplantation]. PMID- 22040865 TI - [Acute respiratory distress syndrome treated by pumpless extracorporeal lung assist device]. PMID- 22040866 TI - [Ischaemic stroke after total knee arthroplasty in patient with atrial fibrillation]. PMID- 22040867 TI - [Cerebral amyloid angiopathy is difficult to diagnose in the intensive care unit]. AB - Cerebral amyloid angiopathy is a common cause of intracerebral haemorrhage in elderly patients. The diagnosis of cerebral amyloid angiopathy is based on the Boston criteria combining clinical and radiological criteria with no other cause of intracerebral haemorrhage. We describe the case of a 60-year-old female admitted to the intensive care unit for agitation and spatial disorientation. She had multiple intracerebral haematomas on brain CT scan. Typical cerebral microbleeds using MRI and the absence of other cause of intracerebral haemorrhage argued in favour of the diagnosis of cerebral amyloid angiopathy. The patient outcome was favourable with a discharge from the intensive care unit on day 16. PMID- 22040868 TI - [Exceptional medical circumstances: interest of an interhospital support strategy within the North Alps emergency trauma network]. AB - The Northern French Alps Emergency Network (RENAU) has a main objective the improvement of the quality of the care in the field of the emergency medical treatment. With this French medical system, we developed a procedure allowing the detachment of a medical-surgical team of the university hospital to help general hospital team in the event of immediate vital emergency situation with untransportable patient. We reported the successful implementation of this support strategy for a 51-year-old patient arrived in a hospital of the network in extremely serious hemodynamic shock due to an important hemorrhagic pericardial effusion with tamponnade 1 day after percutaneous closure of the patent foramen ovale (PFO). PMID- 22040869 TI - [Undesirable events during the perioperative period and communication deficiencies]. AB - In recent decades, anaesthesia and surgery have undergone major scientific and technical developments. However, these improvements have not solved a recurring problem, communication deficiencies within teams in charge of surgical patients. Current figures show that 21% to 65% of accidents and errors in patient management during the perioperative period are related to communication problems. These problems occur when gaps arise in the continuity and coordination of care within teams. Some of the contributing factors to these gaps are emergency status of patients, staff shifts and handovers following patient transfers. To minimize the impact of these phenomena, it is important to improve standardization of information flow within operating theatres and to improve teamwork between anaesthetists and surgeons. This can be done through crew resource management training programs or simulation. This should ultimately contribute to minimise medical error and improve the overall quality of care provided to patients in operating theatres and during all the perioperative period. PMID- 22040870 TI - Effect of interaction between PPARG, PPARA and ADIPOQ gene variants and dietary fatty acids on plasma lipid profile and adiponectin concentration in a large intervention study. AB - Unsaturated fatty acids are ligands of PPAR-gamma, which up-regulates genes involved in fatty acid transport and TAG synthesis and the insulin-sensitising adipokine adiponectin, which activates fatty acid beta-oxidation via PPAR-alpha action in liver. We investigated the effect of dietary fatty acid interaction with PPARG, PPARA and ADIPOQ gene variants on plasma lipid and adiponectin concentrations in the Reading Imperial Surrey Cambridge King's study, a five centre, parallel design, randomised controlled trial of 466 subjects at increased cardiometabolic risk. After a 4-week run-in to baseline, SFA was replaced by MUFA or carbohydrate (low fat) in isoenergetic diets for 24 weeks. Habitual dietary PUFA:SFA ratio*PPARG Pro12Ala genotype interaction influenced plasma total cholesterol (P=0.02), LDL-cholesterol (P=0.002) and TAG (P=0.02) concentrations in White subjects. PPARA Val162Leu*PPARG Pro12Ala genotype interaction influenced total cholesterol (P=0.04) and TAG (P=0.03) concentrations at baseline. After high-MUFA and low-fat diets, total cholesterol and LDL-cholesterol were reduced (P<0.001) and gene*gene interaction determined LDL-cholesterol (P=0.003) and small dense LDL as a proportion of LDL (P=0.012). At baseline, ADIPOQ -10066 G/A A-allele was associated with lower serum adiponectin (n 360; P=0.03) in White subjects. After the high-MUFA diet, serum adiponectin increased in GG subjects and decreased in A-allele carriers (P=0.006 for difference). In GG, adiponectin increased with age after the high MUFA and decreased after the low-fat diet (P=0.003 for difference at 60 years). In conclusion, in Whites, high dietary PUFA:SFA would help to reduce plasma cholesterol and TAG in PPARG Ala12 carriers. In ADIPOQ -10066 GG homozygotes, a high-MUFA diet may help to increase adiponectin with advancing age. PMID- 22040871 TI - Mesodermal retinoic acid signaling regulates endothelial cell coalescence in caudal pharyngeal arch artery vasculogenesis. AB - Disruption of retinoic acid signaling causes a variety of pharyngeal arch artery and great vessel defects, as well as malformations in many other tissues, including those derived from the pharyngeal endoderm. Previous studies implied that arch artery defects in the context of defective RA signaling occur secondary to pharyngeal pouch segmentation defects, although this model has never been experimentally verified. In this study, we examined arch artery morphogenesis during mouse development, and the role of RA in this process. We show in normal embryos that the arch arteries form by vasculogenic differentiation of pharyngeal mesoderm. Using various genetic backgrounds and tissue-specific mutation approaches, we segregate pharyngeal arch artery and pharyngeal pouch defects in RA receptor mutants, and show that RA signal transduction only in pharyngeal mesoderm is required for arch artery formation. RA does not control pharyngeal mesodermal differentiation to endothelium, but instead promotes the aggregation of endothelial cells into nascent vessels. Expression of VE-cadherin was substantially reduced in RAR mutants, and this deficiency may underlie the arch artery defects. The consequences of disrupted mesodermal and endodermal RA signaling were restricted to the 4th and 6th arch arteries and to the 4th pharyngeal pouch, respectively, suggesting that different regulatory mechanisms control the formation of the more anterior arch arteries and pouches. PMID- 22040872 TI - Influence of mesodermal Fgf8 on the differentiation of neural crest-derived postganglionic neurons. AB - The interaction between the cranial neural crest (NC) and the epibranchial placode is critical for the formation of parasympathetic and visceral sensory ganglia, respectively. However, the molecular mechanism that controls this intercellular interaction is unknown. Here we show that the spatiotemporal expression of Fibroblast growth factor 8 (Fgf8) is strategically poised to control this cellular relationship. A global reduction of Fgf8 in hypomorph embryos leads to an early loss of placode-derived sensory ganglia and reduced number of NC-derived postganglionic (PG) neurons. The latter finding is associated with the early loss of NC cells by apoptosis. This loss occurs concurrent with the interaction between the NC and placode-derived ganglia. Conditional knockout of Fgf8 in the anterior mesoderm shows that this tissue source of Fgf8 has a specific influence on the formation of PG neurons. Unlike the global reduction of Fgf8, mesodermal loss of Fgf8 leads to a deficiency in PG neurons that is independent of NC apoptosis or defects in placode-derived ganglia. We further examined the differentiation of PG precursors by using a quantitative approach to measure the intensity of Phox2b, a PG neuronal determinant. We found reduced numbers and immature state of PG precursors emerging from the placode-derived ganglia en route to their terminal target areas. Our findings support the view that global expression of Fgf8 is required for early NC survival and differentiation of placode-derived sensory neurons, and reveal a novel role for mesodermal Fgf8 on the early differentiation of the NC along the parasympathetic PG lineage. PMID- 22040874 TI - Intramedullary nailing of the femur and the systemic activation of monocytes and neutrophils. AB - BACKGROUND: Trauma such as found patients with femur fractures, induces a systemic inflammatory response, which ranges from mild SIRS to ARDS. Neutrophils (i.e. PMN) play an important role in the pathogenesis of this inflammatory condition. Additional activation of PMNs during intramedullary nailing (IMN) is thought to act as a second immunological hit. Damage control orthopedics has been developed to limit this putative exacerbation of the inflammatory response. The hypothesis is tested that IMN exacerbates systemic inflammation, thereby increasing the risk for ARDS. METHODS: Thirty-eight trauma patients who required IMN for femur fracture were included. The development of SIRS and ARDS was recorded. Blood samples were taken prior and 18 hours after IMN. Inflammatory response was analyzed by changes in plasma IL-6 levels, monocyte (HLA-DR) and PMN phenotype (MAC-1 and responsiveness for the innate immune stimulus fMLP in the context of active FcgammaRII). RESULTS: Plasma IL-6 was significantly enhanced in severely injured patients compared to patients with isolated femur fractures and matched controls (P = 0.005; P = 0.018). This enhanced inflammatory tone was associated with a lower percentage HLA-DR positive monocytes (P = 0.002). The systemic PMN compartment was activated, characterized by an increased MAC-1 expression and a significantly decreased sensitivity for the innate stimulus fMLP Interestingly the PMN compartment was not affected by IMN. CONCLUSIONS: Multitrauma patients were characterized by a marked activation of the systemic inflammatory response, associated with a systemic activation of the monocyte and PMN compartments. IMN particularly affected the monocyte arm of the systemic innate immune system. PMID- 22040875 TI - Molecular mechanisms of alpha-crystallinopathy and its therapeutic strategy. AB - alpha-B-Crystallin (CryAB, gene map locus: 11q22.3-q23.1) is a member of the small heat shock protein (HSP) family, a group of proteins that prevent protein aggregation upon exposure of a cell to heat and/or restore the biological activity of cell substrates. The missense mutation and the deletion mutation of CryAB can cause various forms of muscular disorder, including restrictive, hypertrophic, and dilated cardiomyopathies, heart failure, and skeletal muscle weakness. Collectively, these diseases constitute a rare autosomal-dominant inherited disorder called alpha-crystallinopathy (crystallinopathy), also known as desmin-related cardiomyopathy. The disease is a misfolded protein-related disease characterized by the formation of insoluble protein aggregates consisting of the CryAB protein in the patient's cardiomyocytes and skeletal myocytes. The details of crystallinopathy are unclear at the present time; what has been discovered concerning the disease mechanisms underlying crystallinopathy has been through experiments with genetically modified mice such as the CryAB knockout mouse and various mutant CryAB transgenic (TG) mice. Crystallinopathy can be recapitulated in TG mice by expressing the mutant CryAB Arg120Gly (R120G) protein, a causal mutation of crystallinopathy, specifically in the cardiomyocytes. CryAB R120G causes perinuclear formation of aggresomes containing preamyloid oligomer intermediates, which are wellknown as a primary toxic species in neurodegenerative disease. This suggests that crystallinopathy caused by the CryAB mutation could be considered one of the aggresomal and amyloid-related diseases. Moreover, recent findings have indicated that enhancement of HSP induction and inhibition of apoptotic cell death by mitochondrial protection may be a new therapeutic strategy for patients with crystallinopathy. PMID- 22040876 TI - Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model. AB - Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor beta1 (TGF-beta1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with alpha-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-beta1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine. PMID- 22040877 TI - Protective mechanism of andrographolide against carbon tetrachloride-induced acute liver injury in mice. AB - The aim of this study was to investigate the protective effects of andrographolide (AP), a bioactive component isolated from Andrographis paniculata, on carbon tetrachloride (CCl(4))-induced liver injury as well as the possible mechanisms involved in this protection in mice. Acute liver injury was induced by CCl(4) intoxication in mice. Serum biological analysis, lipid peroxides and antioxidant estimation, histopathological studies, reverse transcription polymerase chain reaction (RT-PCR) and Western blot assay were carried out. CCl(4) treatment resulted in severe hepatic injury, as evidenced by significant elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and typical histopathological changes, such as hepatocyte necrosis. Additionally, CCl(4) administration led to oxidative stress in mice, as indicated by a remarkable increase in the hepatic malondialdehyde (MDA) level, together with a significant decrease in liver reduced glutathione (GSH) content. However, CCl(4)-induced hepatotoxicity was significantly attenuated by pretreatment with AP, as demonstrated by significant reduction of serum ALT, AST levels and hepatic MDA activity, along with a remarkable increase in hepatic GSH content. Histopathological changes induced by CCl(4) were also ameliorated by AP pretreatment. The marked increase of tumor necrosis factor alpha (TNF-alpha) induced by CCl(4) was attenuated by AP, and the dramatic elevation of heme oxygenase-1 (HO-1) at transcriptional and protein levels was augmented following AP pretreatment. AP can effectively prevent liver injury induced by CCl(4), which may be due to inhibition of oxidative stress and inflammatory responses. PMID- 22040878 TI - Histological study on the effect of electrolyzed reduced water-bathing on UVB radiation-induced skin injury in hairless mice. AB - Electrolyzed reduced water (ERW), functional water, has various beneficial effects via antioxidant mechanism in vivo and in vitro. However there is no study about beneficial effects of ERW bathing. This study aimed to determine the effect of ERW bathing on the UVB-induced skin injury in hairless mice. For this purpose, mice were irradiated with UVB to cause skin injury, followed by individually taken a bath in ERW (ERW-bathing) and tap water (TW-bathing) for 21 d. We examined cytokines profile in acute period, and histological and ultrastructural observation of skin in chronic period. We found that UVB-mediated skin injury of ERW-bathing group was significantly low compared to TW control group in the early stage of experiment. Consistently, epidermal thickening as well as the number of dermal mast cell was significantly lowered in ERW-bathing group. Defection of corneocytes under the scanning electron microscope was less observed in ERW bathing group than in TW-bathing group. Further, the level of interleukin (IL) 1beta, tumor necrosis factor (TNF)-alpha and IL-12p70 in ERW group decreased whereas those of IL-10 increased. Collectively, our data indicate that ERW bathing significantly reduces UVB-induced skin damage through influencing pro /anti-inflammatory cytokine balance in hairless mice. This suggests that ERW bathing has a positive effect on acute UVB-mediated skin disorders. This is the first report on bathing effects of ERW in UVB-induced skin injury. PMID- 22040879 TI - Cyclic Limulus anti-lipopolysaccharide (LPS) factor-derived peptide CLP-19 antagonizes LPS function by blocking binding to LPS binding protein. AB - Inflammation and septic shock due to endotoxins from Gram-negative bacteria infection continue to pose significant challenges to human healthcare. It is, therefore, necessary to develop therapeutic strategies targeting endotoxins, such as lipopolysaccharide (LPS), to prevent their potentially systemic effects. Pathogenesis due to Gram-negative bacteria involves LPS binding to the host LPS binding protein (LBP), causing detrimental downstream signaling cascades. Our previous study showed that CLP-19, a synthetic peptide derived from the Limulus anti-LPS factor (LALF), could effectively neutralize LPS toxicity; however, the detailed mechanisms underlying this anti-LPS effect remained unexplained. Thus, we carried out investigations to determine how the CLP-19 neutralizes LPS toxicity. CLP-19 was found to block LPS binding to LBP in a dose-dependent manner, as evidenced by competitive enzyme-linked immunosorbent assay (ELISA). In peripheral blood mononuclear cells, CLP-19 blocked LPS-induced phosphorylation of mitogen activated protein kinase (MAPK) signaling proteins p38, extracellular signal-regulating kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK)1/2. Furthermore, CLP-19 potency in LPS antagonism in vitro and in vivo was directly associated with its ability to block the LPS-LBP interaction. Taken together, the results suggested that CLP-19's inhibitory effect on LPS-LBP binding and on the subsequent MAPK pathway signaling may be responsible for its anti-LPS mechanism. This peptide appears to represent a potential therapeutic agent for clinical treatment of sepsis. PMID- 22040880 TI - Rho kinase inhibition by fasudil has anti-inflammatory effects in hypercholesterolemic rats. AB - Inhibition of Rho kinase (ROCK) ameliorates many cardiovascular dysfunctions. The aim of the current study is to investigate the anti-inflammatory effects of fasudil, a selective ROCK inhibitor, on high cholesterol diet-induced hypercholesterolemic rats and its possible mechanisms. In hypercholesterolemic rats, we found the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and several inflammatory markers including interleukin (IL)-8, IL-6, C-reaction protein (CRP) and soluble intercellular adhesion molecule (sICAM)-1 significantly elevated, while those of high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) decreased. Moreover, mRNA expressions of ROCK and nuclear factor-kappa B (NF-kappaB) and activity of ROCK in thoracic aorta were greatly up-regulated. Remarkably, administrating fasudil (10, 30 mg/kg per day) or simvastatin (10 mg/kg per day) to hypercholesterolemic rats for 2 weeks, activation of ROCK and NF-kappaB in thoracic aorta were suppressed, status of dyslipidemia were improved and inflammatory markers lowered. From the histopathological examination, fasudil treatment was found to lessen the thickening noted in the aortic intima and media of the hypercholesterolemic rats. These results suggested fasudil-induced inhibition of ROCK may improve lipid metabolism and has anti-inflammatory effect, which might expand the clinical application of fasudil as a new therapy for hypercholesterolemia and preventing the development of atherosclerosis. PMID- 22040881 TI - The effects of gap junction modulators on the rhythmic contractions in aortas isolated from rats subjected with sinoaortic denervation. AB - Following sinoaortic denervation (SAD) rats present intense arterial pressure lability without sustained hypertension. This study aimed to verify the effects of heptanol (a putative gap-junction blocker) and tetraethylammonium (TEA, a putative gap-junction activator) on rhythmic contractions (RCs) and vascular reactivity in the aortas isolated from SAD and Sham-operated (SO) rats. Rhythmic contractions were observed with phenylephrine in endothelium-removed aortic rings from SAD rats. We evaluated the effects of the gap-junction modulators heptanol or TEA on the frequency and amplitude of these oscillations. Additionally, concentration-response curves were constructed to TEA and KCl and in pre contracted arteries (with phenylephrine or KCl) to heptanol in order to verify the effects of those gap-junction modulators. Comparatively, rhythmic contractions were observed in 10/10 SAD rat aortas vs. 2/10 controls. Heptanol decreased the frequency of oscillations in a concentration-dependent manner. TEA increased the amplitude and frequency of RCs. In the experiments of concentration response curves to TEA, the maximal contractile effect was similar in both groups, although the potency was lower in SAD than in SO rat aortas. The relaxation to heptanol was different between the groups only after pre contraction induced by phenylephrine. Heptanol showed higher potency in SAD as compared to SO rat aortas. In conclusion, arterial pressure lability occurs only in SAD rats, and their isolated aortas exhibit intense RCs. These RCs seem to be dependent of the gap-junction communication, since these oscillations are intensified by TEA and inhibited by heptanol. After SAD, aortas are more sensitive to heptanol and less sensitive to TEA. PMID- 22040882 TI - Antihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive rats. AB - To determine whether the antihypertensive effect of nattokinase is associated with the protease activity of this enzyme, we compared nattokinase with the fragments derived from nattokinase, which possessed no protease activity, in terms of the effect on hypertension in spontaneously hypertensive rats (SHR). In the continuous oral administration test, the groups were given a basic diet alone (control), the basic diet containing nattokinase (0.2, 2.6 mg/g diet) or the basic diet containing the fragments derived from nattokinase (0.2, 0.6 mg/g diet). The group fed the basic diet containing high-dosage nattokinase (2.6 mg/g diet) showed significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma fibrinogen level, compared with control group and no influence on activities of renin and angiotensin-converting enzyme (ACE, EC 3.4.15.1), and plasma angiotensin II level in the renin-angiotensin system. The treatment of the basic diet containing high-dosage fragments (0.6 mg/g diet) significantly decreased SBP, DBP and plasma angiotensin II level in plasma but the treatment did not influence on plasma fibrinogen level. These results suggest that nattokinase and its fragments are different from each other in the mechanism to reduce hypertension. Nattokinase, retained its protease activity after absorbance across the intestines, may decrease blood pressure through cleavage of fibrinogen in plasma. The fragments, which absorbed as nattokinase-degradation products, prevents the elevation of plasma angiotensin II level to suppress hypertension. PMID- 22040883 TI - Oral administration of ethyl acetate-soluble portion of Terminalia chebula conferring protection from streptozotocin-induced diabetic mellitus and its complications. AB - Terminalia chebula has been widely used in India as a folk medicine. This study investigated the in vivo anti-hyperglycemia and anti-diabetic complication effects of the EtOAc-soluble portion of ethanolic extract of T. chebula fruit (EETC) containing 29.4% chebulic acid. Rats were divided into non-diabetic, untreated diabetic and diabetic groups. Streptozotocin (40 mg/kg body weight (BW))-induced diabetic rats were orally administered the aminoguanidine (100 mg/kg BW), high dose (500 mg/kg BW; HEETC) and low dose (100 mg/kg BW; LEETC) for 13 weeks. HEETC administration reduced the levels of blood glucose and serum lipids, decreased malondialdehyde concentrations of serum and thoracic aorta in diabetic rats, and significantly improved serum biochemical values and the pathomorphological changes of the liver and kidney in diabetic rats. Also, HEETC decreased the advanced glycation end products (AGEs) distribution in testis seminiferous tubules. Therefore, HEETC has a merit to be a potent candidate to control glycemic and diabetic complications. PMID- 22040884 TI - Scattered regulatory regions of the chicken immunoglobulin-beta gene and two adjacent promoters of ubiquitously expressed genes interact with the immunoglobulin-beta promoter in DT40 cells. AB - Recent studies indicate that several transcription units assemble to form a 'transcription factory' where active transcription occurs in the nuclei. Previously, we generated chicken B-lymphocyte-derived DT40 cells lacking six transcriptional regulatory regions scattered in and around the immunoglobulin (Ig)-beta gene. The deletions caused a complete shut down of transcription and epigenetic regulation of the Ig-beta gene, demonstrating that the scattered regulatory regions cooperated in the transcriptional and epigenetic regulation of the gene. However, the in vivo 3-dimensional spatial relationships between the Ig beta promoter and these six regulatory regions were not investigated. In this study, we used chromosome conformation capture (3C) technology and demonstrated that the Ig-beta promoter physically interacted with the scattered regulatory regions. We found that the Ig-beta promoter also interacted with two downstream promoters of ubiquitously expressed genes, rad motif 1 (RDM1) and Plekhm1, to form a transcription factory, but not with three ubiquitously expressed genes, BAF60b, p45/SUG, and RRMJ3, located upstream of the Ig-beta gene. In this factory, the chromatin from the three promoters and the scattered regulatory regions of the Ig-beta gene formed a complex structure with many chromatin loops. PMID- 22040885 TI - Sensitive fern (Onoclea sensibilis) extract suppresses proliferation and migration of vascular smooth muscle cells inflamed by neighboring macrophages. AB - Vascular smooth muscle cell (SMC) migration and proliferation contribute to arterial wound repair and thickening of the intimal layer in atherosclerosis. SMC can physically interact with monocytes and macrophages within the intima. This study evaluated whether macrophages modulated proliferation and migration of SMC in close proximity, which was suppressed by 1-25 ug/ml sensitive fern (Onoclea sensibilis) extract (SFE) inhibiting protein-tyrosine phosphatase-1B activity. The addition of conditioned media of THP-1-derived macrophages substantially promoted human aortic smooth muscle cell (HAoSMC) proliferation by ~30%. HAoSMC proliferation was significantly attenuated by >=10 ug/ml SFE most likely due to its diminution of platelet derived growth factor (PDGF)-BB secreted by neighbor macrophages. HAoSMC migration was also enhanced by culturing in THP-1 macrophage conditioned media, as evidenced by a scratch wound assay. However, the presence of >=10 ug/ml SFE did not allow such migaration. When SFE was treated to THP-1 macrophages, the secretion of the adipokines, visfatin and resistin, was abrogated. SFE at 1-25 ug/ml dose-dependently diminished resistin-stimulated secretion of collagen IV and connective tissue growth factor (CTGF) in HAoSMC, indicating that macrophage resistin plays a role in the extracellular matrix (ECM) production of vascular SMC. These results demonstrate that SFE disturbed proliferation and migration of SMC instigated by inflammatory macrophages in close proximity. Therefore, this study provides novel information that SFE has the potential capability to prevent atherosclerosis involving SMC proliferation, migration and fibrogenic activation within the vessels. PMID- 22040886 TI - Dihydrotestosterone inhibits interleukin-1alpha or tumor necrosis factor alpha induced proinflammatory cytokine production via androgen receptor-dependent inhibition of nuclear factor-kappaB activation in rheumatoid fibroblast-like synovial cell line. AB - Rheumatoid arthritis (RA) is a disease with significant gender differences in its prevalence and clinical features. Interleukin (IL)-1 and tumor necrosis factor (TNF) alpha produced by synoviocytes are principle inflammatory and destructive mediators of RA. We found that a potent androgen, 5alpha-dihydrotestosterone (DHT) inhibits IL-1alpha-induced production and mRNA expression of IL-8, IL-6 and IL-1beta from RA patient-derived fibroblast-like synovial cell line MH7A. Promoter analysis of the IL-8 gene revealed that nuclear factor (NF)-kappaB activation is critical for its transcriptional activation by IL-1alpha, and DHT inhibited the IL-1alpha-induced NF-kappaB activation in a manner dependent on the androgen receptor (AR). DHT also inhibited the effects of TNFalpha on the cells overexpressed with AR, indicating that sufficient expression level of functional AR was necessary for the inhibitory effect of DHT on TNFalpha. These results suggest that androgen contributes to the prevention against RA and its gender difference by inhibiting IL-1alpha or TNFalpha-induced proinflammatory cytokine production from synovial fibroblast-like cells by inhibiting NF-kappaB activation in a manner depending on AR. PMID- 22040887 TI - Factors affecting the absorption of nilvadipine from disintegration-controlled matrix tablet in dogs. AB - The purpose of this study was to investigate the pharmacokinetics of nilvadipine (NiD) from disintegration-controlled matrix tablets (DCMT). A further purpose was to clarify biological factors that affect the absorption of NiD from DCMT. Two DCMT formulations, which released approximately 80% of NiD in 6 h (DCMT-M) and 10 h (DCMT-S) in vitro, were prepared and compared with immediate-release (IR) tablets. The T(max) and mean residence time from DCMT-M and DCMT-S were significantly longer than those from IR tablets in fasted dogs. The area under the plasma concentration-time curve (AUC) (0-infinity) from DCMT-M in both fed and fasted dogs and IR tablets were comparable in both fed and fasted dogs, indicating complete drug release and absorption without food effect. In contrast, the AUC from DCMT-S was significantly lower than the AUC from IR tablets in fasted dogs. The AUC from DCMT-S increased in fed dogs, but it was still lower than the AUC from IR tablets. In vivo absorption profiles calculated by deconvolution method suggested that the duration of drug absorption from DCMT-S was prolonged from 6 h in fasted condition to 8 h in fed condition, suggesting longer gastro-intestinal (GI) transit time in fed condition allowed longer drug release duration from DCMT-S. Regional drug absorption was also evaluated using NiD solution. The results indicated NiD was almost completely absorbed from canine jejunum, ileum and colon, indicating drug permeation is not a rate limiting factor of NiD absorption. Therefore, limited GI transit time is the primary factor that affects the drug release from DCMT and subsequent NiD absorption. PMID- 22040888 TI - Effect of aminoguanidine on ischemia/reperfusion injury in rat small intestine. AB - Ischemia/reperfusion (I/R) injury is induced by reactive oxygen species (ROS). During intestinal I/R, the amount of nitric oxide (NO), which is a ROS, is increased. In this study, we examined the protection against I/R injury by inhibition of NO generation. Wistar/ST rats were exposed to 1 h of ischemia, followed by reperfusion for 4 h. The rats were intravenously injected with 100 mg/kg aminoguanidine (AG), which is a selective inducible NO synthase (iNOS) inhibitor, for 5 min before ischemia. The increase in NO(2)(-) by intestinal I/R was significantly inhibited by AG 1 h after reperfusion. Moreover, the increase in area under curve of 0 to 1 h after reperfusion (AUC(0-1)) of paracellular marker was inhibited. However, 3 h after reperfusion, the survival ratio of rats was significantly decreased in the intestinal I/R condition with AG. The amount of NO(2)(-) and AUC of 3 to 4 h after reperfusion (AUC(3-4)) of paracellular marker in intestinal I/R groups were increased by AG compared with those in the I/R condition without AG 3 h after reperfusion. These data indicated that AG, which was given by single pre-administration, can clearly inhibit intestinal I/R injury 1 h after reperfusion. However, the injury occurs again 3 h after reperfusion and grows worse. PMID- 22040889 TI - Absorption and excretion of ascorbic acid alone and in acerola (Malpighia emarginata) juice: comparison in healthy Japanese subjects. AB - It has been suggested that some food components, such as bioflavonoids, affect the bioavailability of ascorbic acid in humans. Since little is known in Japan about the effective intake of this dietary requirement, we tested young Japanese males after the ingestion of commercial ascorbic acid or acerola (Malpighia emarginata DC.) juice to compare the quantities absorbed and excreted. Healthy Japanese subjects received a single oral dose of ascorbic acid solution (50, 100, 200 or 500 mg) and received distilled water as a reference at intervals of 14 d or longer. All subjects were collected blood and urine until 6 h after ingestion and evaluated for time-dependent changes in plasma and urinary ascorbic acid levels. Predictably, the area under the curve (AUC) values in plasma and urine after ingestion increased dose-dependently. Next, each subject received diluted acerola juice containing 50 mg ascorbic acid. Likewise, their plasma and urinary ascorbic acid concentrations were measured. In plasma, the AUC value of ascorbic acid after ingestion of acerola juice tended to be higher than that from ascorbic acid alone. In contrast, the urinary excretion of ascorbic acid at 1, 2 and 5 h after ingestion of acerola juice were significantly less than that of ascorbic acid. These results indicate that some component of acerola juice favorably affected the absorption and excretion of ascorbic acid. PMID- 22040890 TI - Involvement of c-Met- and phosphatidylinositol 3-kinase dependent pathways in arsenite-induced downregulation of catalase in hepatoma cells. AB - Catalase protects cells from reactive oxygen species-induced damage by catalyzing the breakdown of hydrogen peroxide to oxygen and water. Arsenite decreases catalase activity; it activates phosphatidylinositol 3-kinase (PI3K) and its key downstream effector Akt in a variety of cells. The PI3K pathway is known to inhibit catalase expression. c-Met, an upstream regulator of PI3K and Akt, is also involved in the regulation of catalase expression. To examine the involvement of c-Met and PI3K pathways in the arsenite-induced downregulation of catalase, catalase mRNA and protein expression were analyzed in the human hepatoma cell line HepG2 treated with arsenite and either an inhibitor of c-Met (PHA665752 (PHA)) or of PI3K (LY294002 (LY)). Arsenite treatment markedly activated Akt and decreased the levels of both catalase mRNA and protein. Both PHA and LY attenuated arsenite-induced activation of Akt. PHA and LY treatment also prevented the inhibitory effect of arsenite on catalase protein expression but did not affect the level of catalase mRNA. These findings suggest that arsenite-induced inhibition of catalase expression is regulated at the mRNA and post-transcriptional levels in HepG2 cells, and that the post-transcriptional regulation is mediated via c-Met- and PI3K-dependent mechanisms. PMID- 22040891 TI - Excessive expression of hippocampal ezrin is induced by intrastriatal injection of 6-hydroxydopamine. AB - Accumulating evidence in humans demonstrates that visuo-spatial deficits are the most consistently reported cognitive abnormalities in Parkinson's disease (PD). Ezrin, radixin, and moesin are collectively known as ERM proteins. Although ERM proteins have important implications in cell-shape determination and relevant signaling pathway, they have not been studied in the hippocampus in association with visuo-spatial memory impairments. The purpose of the present study is to examine whether the expression level of ERM proteins in the hippocampus is changed by an intrastriatal injection of 6-hydroxydopamine (6-OHDA) in mice. The intrastriatal injection of 6-OHDA induced partial dopaminergic deficits and spatial memory impairments. We also found that ezrin was increased in the hippocampus by the microinjection of 6-OHDA. On the other hand, protein levels of radixin and moesin were not influenced by 6-OHDA lesions. These results suggest that excessive ezrin may be related to visuo-spatial memory impairments. PMID- 22040892 TI - Evidence for neuroprotective effect of sulbutiamine against oxygen-glucose deprivation in rat hippocampal CA1 pyramidal neurons. AB - Hippocampus is one of the earliest brain regions that gets affected by ischemia, however, no pharmacological therapy exists yet that can fully counteract the ischemic damage. Here we study the effect of sulbutiamine, a synthetic thiamine analogue that can cross the blood-brain barrier easily, on hippocampal neurons under an in vitro model of ischemia, oxygen-glucose deprivation (OGD). We find that exposure to OGD in the presence of sulbutiamine significantly increases neuronal viability and enhances electrophysiological properties such as excitatory synaptic transmissions and intrinsic neuronal membrane input resistance in a concentration-dependent manner. Overall, here we report, for the first time, the neuroprotective evidence of sulbutiamine on hippocampal CA1 pyramidal neurons under OGD, which may have beneficial implications as a possible therapeutic agent/substance against ischemic insult. PMID- 22040893 TI - The relationship between treatment time of gemcitabine and development of hematologic toxicity in cancer patients. AB - Although gemcitabine is frequently used in the treatment of cancer, it is associated with myelosuppression. An animal study showed that the tolerability of gemcitabine varied with changes in treatment time; however, no clinical data have verified this finding. The purpose of this study was to determine the relationship between treatment time and development of hematologic toxicity in patients treated with gemcitabine. Gemcitabine-induced hematologic toxicity was retrospectively investigated in 77 patients. Patients were divided into two treatment-time groups: 9:00 and 15:00. Hematologic toxicity was evaluated on day 8 and 15 after treatment. On day 8 and 15, the changing count of white blood cells was significantly reduced in patients treated at 15:00 compared with those treated at 9:00 (p<0.01 and p<0.05, respectively). On days 8 and 15, the changing count of platelet was significantly reduced in patients treated at 15:00 compared with those treated at 9:00 (p<0.05). The incident of over common terminology criteria for adverse events (CTCAE) grade 2 white blood cell decreased was significantly reduced in patients treated at 15:00 compared with those treated at 9:00 (p=0.048, odds ratio=2.92). In conclusion, this cohort study demonstrated that gemcitabine-induced hematologic toxicity could be alleviated by treating patients at 9:00. PMID- 22040894 TI - Manassantin A isolated from Saururus chinensis inhibits 5-lipoxygenase-dependent leukotriene C4 generation by blocking mitogen-activated protein kinase activation in mast cells. AB - In this study, manassantin A (Man A), an herbal medicine isolated from Saururus chinensis (S. chinensis), markedly inhibited 5-lipoxygenase (5-LO)-dependent leukotriene C(4) (LTC(4)) generation in bone marrow-derived mast cells (BMMCs) in a concentration-dependent manner. To investigate the molecular mechanisms underlying the inhibition of LTC(4) generation by Man A, we assessed the effects of Man A on phosphorylation of cytosolic phospholipase A(2) (cPLA(2)) and mitogen activated protein kinases (MAPKs). Inhibition of LTC(4) generation by Man A was accompanied by a decrease in cPLA(2) phosphorylation, which occurred via the MAPKs including extracellular signal-regulated protein kinase-1/2 (ERK1/2) as well as p38 and c-Jun N-terminal kinase (JNK) pathways. Taken together, the present study suggests the Man A represents a potential therapeutic approach for the treatment of airway allergic-inflammatory diseases. PMID- 22040895 TI - Introduction: a life course perspective on activity and neurocognitive health. PMID- 22040896 TI - A review of the relation of aerobic fitness and physical activity to brain structure and function in children. AB - A growing number of schools have increasingly de-emphasized the importance of providing physical activity opportunities during the school day, despite emerging research that illustrates the deleterious relationship between low levels of aerobic fitness and neurocognition in children. Accordingly, a brief review of studies that link fitness-related differences in brain structure and brain function to cognitive abilities is provided herein. Overall, the extant literature suggests that childhood aerobic fitness is associated with higher levels of cognition and differences in regional brain structure and function. Indeed, it has recently been found that aerobic fitness level even predicts cognition over time. Given the paucity of work in this area, several avenues for future investigations are also highlighted. PMID- 22040897 TI - Physical activity associated with increased resting-state functional connectivity in multiple sclerosis. AB - Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, resulting in physical, cognitive and affective disturbances, with notable declines in the ability to learn and retain new information. In this study, we examined if higher levels of physical activity in MS individuals were associated with an increased resting-state connectivity of the hippocampus and cortex, resulting in better performance on a task of episodic memory. Forty-five individuals with a clinically definite diagnosis of MS were recruited for the study. Consistent with previous reports, hippocampus was functionally connected to the posteromedial cortex, parahippocampal gyrus, superior frontal gyrus, and the medial frontal cortex. Higher levels of physical activity in MS patients were associated with an increased coherence between the hippocampus and the posteromedial cortex (PMC). The increased connectivity between these two regions, in turn, was predictive of better relational memory, such that MS patients who showed an increased coherence between the left (not right) hippocampus and the PMC also showed better relational memory. Results of the study are interpreted in light of the challenge of disentangling effects of physical activity from effects of disease severity and its neuropathological correlates. PMID- 22040898 TI - Late-life social activity and cognitive decline in old age. AB - We examined the association of social activity with cognitive decline in 1138 persons without dementia at baseline with a mean age of 79.6 (SD = 7.5) who were followed for up to 12 years (mean = 5.2; SD = 2.8). Using mixed models adjusted for age, sex, education, race, social network size, depression, chronic conditions, disability, neuroticism, extraversion, cognitive activity, and physical activity, more social activity was associated with less cognitive decline during average follow-up of 5.2 years (SD = 2.7). A one point increase in social activity score (range = 1-4.2; mean = 2.6; SD = 0.6) was associated with a 47% decrease in the rate of decline in global cognitive function (p < .001). The rate of global cognitive decline was reduced by an average of 70% in persons who were frequently socially active (score = 3.33, 90th percentile) compared to persons who were infrequently socially active (score = 1.83, 10th percentile). This association was similar across five domains of cognitive function. Sensitivity analyses revealed that individuals with the lowest levels of cognition or with mild cognitive impairment at baseline did not drive this relationship. These results confirm that more socially active older adults experience less cognitive decline in old age. PMID- 22040899 TI - Association of crossword puzzle participation with memory decline in persons who develop dementia. AB - Participation in cognitively stimulating leisure activities such as crossword puzzles may delay onset of the memory decline in the preclinical stages of dementia, possibly via its effect on improving cognitive reserve. We followed 488 initially cognitively intact community residing individuals with clinical and cognitive assessments every 12-18 months in the Bronx Aging Study. We assessed the influence of crossword puzzle participation on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Crossword puzzle participation at baseline delayed onset of accelerated memory decline by 2.54 years. Inclusion of education or participation in other cognitively stimulating activities did not significantly add to the fit of the model beyond the effect of puzzles. Our findings show that late life crossword puzzle participation, independent of education, was associated with delayed onset of memory decline in persons who developed dementia. Given the wide availability and accessibility of crossword puzzles, their role in preventing cognitive decline should be validated in future clinical trials. PMID- 22040900 TI - Apathy and depression: separate factors in Parkinson's disease. AB - The objective of this study was to test the hypothesis that apathy and depression are dissociable in Parkinson disease (PD) by conducting a confirmatory factor analysis (CFA) of items from two commonly used mood scales. A total of 161 non demented PD patients (age = 64.1; +/- 8.4 years) were administered the Apathy Scale and the Beck Depression Inventory-II. Items were hypothesized to load onto four factors: (1) an apathy factor representing loss of motivation, (2) dysphoric mood factor representing sadness and negativity, (3) loss of interest/pleasure factor representing the features common to both apathy and depression, and (4) a somatic factor representing bodily complaints. Results indicated a good fit for the overall CFA model, chi2 (128, N = 146) = 194.9; p<.01. RMSEA was .060 (p = .16). The four-factor model was significantly better than all alternative nested models at p < .001, including an overarching single factor model, representing "depression." Results support the concept that apathy and depression are discrete constructs. We suggest a "factor based" scoring of the Apathy Scale and Beck Depression Inventory-II that disentangles symptoms related to apathy, depression, overlapping symptoms, and somatic complaints. Such scoring may be important in providing useful information regarding differential treatment options. PMID- 22040901 TI - Reaction time and rapid serial processing measures of information processing speed in multiple sclerosis: complexity, compounding, and augmentation. AB - Information processing speed is frequently cited as the primary cognitive domain impacted by multiple sclerosis (MS) and is usually evaluated with reaction time (RT) or rapid serial processing (RSP) measures. The present study compared the efficacy of RT and RSP measures to distinguish between patients with MS (N = 42) and healthy controls (N = 40). The RT measure was patterned after the Computerized Tests of Information Processing and included measures of simple, choice, and semantic RT. The RSP measures consisted of the Symbol Digit Modalities Test (SDMT) and the Stroop Test. Substantial differences in information processing speed between patients and controls were found on all tests, with slightly larger effect sizes for RSP measures than RT measures and for the SDMT than the Stroop Test. Binary logistic regression analyses showed RSP measures performed better than RT measures at distinguishing patients from controls, and likewise, the SDMT score performed better than the scores derived from the Stroop Test. Results are discussed in the context of three effects associated with common measures of processing speed: complexity, compounding, and augmentation. PMID- 22040902 TI - Genetic and histologic evidence for autophagy in asthma pathogenesis. PMID- 22040903 TI - Berries contamination by microfungi in Slovakia vineyard regions: impact of climate conditions on microfungi biodiversity. AB - BACKGROUND: Weather conditions can selectively promote the growth of particular fungal species, which cause rotting and spoilage of grape berries before harvest. The presence of pathogenic fungi can lead to the development of opportunist microfungi that can produce mycotoxins and cause grapes and wine contamination. OBJECTIVE: The variation of climatic conditions allowed to design a pilot study and address relevant questions for risk assessment of climate related mycotoxins production in grapes and in wine. METHODS: Microfungi contaminating berries during the vegetative period of year 2008 and 2009 in vineyards regions of Slovakia at the early veraison and at the ripening in harvest time have been identified. RESULTS: Spoilage fungi were more abundant in veraison for both years in all the studied geographical regions, with an average temperature of 20 degrees C, humidity between 60 and 80%, and precipitation in the range 6-5mm. Much more strains of toxigenic fungi were found during veraison and ripening in the case of a year temperature variation in the range 17-22.5 degrees C, humidity values ranging from 58 to 80% and precipitations in the range 0.7-8.4mm. CONCLUSIONS: The results suggest that there is an effect of the climatic conditions on microfungi biodiversity. PMID- 22040904 TI - Three new acetylated benzyl-beta-resorcylate glycosides from Cassia obtusifolia. AB - Three new acetylated benzyl-beta-resorcylate glycosides (1-3) were isolated from seeds of Cassia obtusifolia. Their structures were determined on the basis of the spectroscopic methods and physicochemical properties as 2-benzyl-4,6-dihydroxy benzoic acid-6-O-[2,6-O-diacetyl]-D-glucopyranoside (1), 2-benzyl-4,6-dihydroxy benzoic acid-6-O-[3,6-O-diacetyl]-D-glucopyranoside (2) and 2-benzyl-4, 6 dihydroxy benzoic acid-6-O-[4,6-O-diacetyl]-D-glucopyranoside (3), respectively. PMID- 22040905 TI - Moving and being moved: differences in cerebral activation during recollection of whole-body motion. AB - While moving through the world, humans as well as animals can make use of motion cues during both active and passive whole-body motion to track their own position in space. However, the functional neuroanatomy of self-motion processing remains poorly understood. In the present study we aimed to characterize brain networks reflecting whole-body self-motion experience. We used retrieval of previously experienced events, which is known to involve cortical representations of the modalities used to perceive these events. Recollection of self-motion experience may thus engage motor and sensory brain areas, reflecting the active or passive nature of the experienced movement, but may engage also common brain areas processing self-motion. We further compared the retrieval networks of self- and observed motion: even though actual action observation has been shown to recruit brain networks similar to those active during mental simulation, it is unclear to which extent recollection networks of these experiences overlap. Brain activation patterns were recorded using fMRI during mental simulation of recent episodes of (1) experiencing linear whole-body motion (active locomotion and passive transport) and (2) observing another person performing the same tasks. Following the experiential phase, participants recalled the episodes during a MR session. We found that primary sensorimotor brain areas dominate the composition of the recollection network of active walking, while recalling passive transport recruits higher level association areas. Common to both self-motion conditions was activation in the medial temporal lobe. Recollection of self-experienced and observed movement overlapped in motor planning areas. Our results provide evidence that the medial temporal lobe is specifically relevant for retrieval of self-motion information and that motor coding during action observation is reflected in recollection networks. PMID- 22040906 TI - Abnormal nuclear envelope in the cerebellar Purkinje cells and impaired motor learning in DYT11 myoclonus-dystonia mouse models. AB - Myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonia. DYT11 M-D is caused by mutations in SGCE which codes for E sarcoglycan. SGCE is maternally imprinted and paternally expressed. Abnormal nuclear envelope has been reported in mouse models of DYT1 generalized torsion dystonia. However, it is not known whether similar alterations occur in DYT11 M D. We developed a mouse model of DYT11 M-D using paternally inherited Sgce heterozygous knockout (Sgce KO) mice and reported that they had myoclonus and motor coordination and learning deficits in the beam-walking test. However, the specific brain regions that contribute to these phenotypes have not been identified. Since E-sarcoglycan is highly expressed in the cerebellar Purkinje cells, here we examined the nuclear envelope in these cells using a transmission electron microscope and found that they are abnormal in Sgce KO mice. Our results put DYT11 M-D in a growing family of nuclear envelopathies. To analyze the effect of loss of E-sarcoglycan function in the cerebellar Purkinje cells, we produced paternally inherited cerebellar Purkinje cell-specific Sgce conditional knockout (Sgce pKO) mice. Sgce pKO mice showed motor learning deficits, while they did not show abnormal nuclear envelope in the cerebellar Purkinje cells, robust motor deficits, or myoclonus. The results suggest that E-sarcoglycan in the cerebellar Purkinje cells contributes to the motor learning, while loss of E-sarcoglycan in other brain regions may contribute to nuclear envelope abnormality, myoclonus and motor coordination deficits. PMID- 22040907 TI - Cyclic stretch increases splicing noise rate in cultured human fibroblasts. AB - BACKGROUND: Mechanical forces are known to alter the expression of genes, but it has so far not been reported whether they may influence the fidelity of nucleus based processes. One experimental approach permitting to address this question is the application of cyclic stretch to cultured human fibroblasts. As a marker for the precision of nucleus-based processes, the number of errors that occur during co-transcriptional splicing can then be measured. This so-called splicing noise is found at low frequency in pre-mRNA splicing. FINDINGS: The amount of splicing noise was measured by RT-qPCR of seven exon skips from the test genes AATF, MAP3K11, NF1, PCGF2, POLR2A and RABAC1. In cells treated by altered uniaxial cyclic stretching for 18 h, a uniform and significant increase of splicing noise was found for all detectable exon skips. CONCLUSION: Our data demonstrate that application of cyclic stretch to cultured fibroblasts correlates with a reduced transcriptional fidelity caused by increasing splicing noise. PMID- 22040908 TI - Individual and institutional factors affecting cardiac monitoring in coronary care units: a national survey of Chinese nurses. AB - BACKGROUND: As cardiovascular diseases have become the leading cause of death in many countries including China, nurses are increasingly required to be abreast of technological advances and the skills necessary to manage this increasing health care problem. Chinese nurses are under pressure to provide skilled electrocardiography monitoring, and be sufficiently skilled to detect myocardial ischemia and infarction, in this large patient population. This presents a challenge for the nursing profession in China, particularly for nurses working in coronary care in a country where advancement has been so rapid, yet little research has been conducted or reported in the literature. OBJECTIVES: The two main objectives were: to explore the demographic and educational factors that affect the use of ST-segment monitoring and correct electrode placement by CCU/ICU nurses in China; and to explore the factors both individual and institutional that affect monitoring and lead placement. METHODS: A self administered questionnaire was distributed to nurses in 126 randomly selected tertiary hospitals, which were stratified into three homogeneous regions across China. The instrument examined demographics, information about hospitals, electrocardiogram devices, current practice patterns and perceptions toward monitoring and lead placement. Data from 734 nurses and 59 nurse managers from 59 hospitals were analyzed using t-tests, ANOVA, Chi-square test and logistic regression. RESULTS: Electrocardiogram monitoring was used to detect myocardial ischemia by 43.7% of respondents, and 35.1% selected leads according to electrocardiogram or angiography findings. Most (70%) agreed that monitoring for acute coronary syndrome was important, while 39.2% did so, and 15.7% were able to identify correct placement. Logistic regression revealed a significant relationship between the uses of ST-segment monitoring and number of hospital beds, continuing education and a belief in its use and ease of use. Correct electrode placement was significantly correlated with respondents from university hospitals, hospitals with more acute coronary syndrome admissions and more independent thinking nurses. CONCLUSIONS: Despite best practice evidence, less than half of the sample used electrocardiogram monitoring to detect myocardial ischemia and the majority could not identify correct electrode placement, while ST-segment monitoring was not used routinely. This paper highlights the need for improvements in education both in universities and hospitals and discussion addresses conventions in units, which inhibit development of nurses' skills. PMID- 22040909 TI - Release of monomeric sugars from Miscanthus sinensis by microwave-assisted ammonia and phosphoric acid treatments. AB - Microwave-assisted ammonium hydroxide (NH4OH) followed by phosphoric acid (H3PO4) treatments were used to release monomeric sugars from Miscanthus sinensis grown in Cha-Chueng-Sao province, Thailand. Treatment with 1.0% (w/v) NH4OH, 15:1 liquid-to-solid ratio (LSR) at 120 degrees C temperature for 15 min liberated 2.9 g of monomeric sugars per 100 g of dried biomass, whereas the corresponding yield for a treatment with 1.78% v/v H3PO4, 15:1 LSR at 140 degrees C for 30 min was 62.3 g/100 g. The two-stage pretreatment, treatment with NH4OH at 120 degrees C temperature for 15 min followed by treatment with H3PO4 at 140 degrees C for 30 min, impressively provided the highest total monomeric sugar yield of 71.6 g/100 g dried biomass. PMID- 22040910 TI - Eph/ephrin signaling in epidermal differentiation and disease. AB - Eph receptor tyrosine kinases mediate cell-cell communication by interacting with ephrin ligands residing on adjacent cell surfaces. In doing so, these juxtamembrane signaling complexes provide important contextual information about the cellular microenvironment that helps orchestrate tissue morphogenesis and maintain homeostasis. Eph/ephrin signaling has been implicated in various aspects of mammalian skin physiology, with several members of this large family of receptor tyrosine kinases and their ligands present in the epidermis, hair follicles, sebaceous glands, and underlying dermis. This review focuses on the emerging role of Eph receptors and ephrins in epidermal keratinocytes where they can modulate proliferation, migration, differentiation, and death. The activation of Eph receptors by ephrins at sites of cell-cell contact also appears to play a key role in the maturation of intercellular junctional complexes as keratinocytes move out of the basal layer and differentiate in the suprabasal layers of this stratified, squamous epithelium. Furthermore, alterations in the epidermal Eph/ephrin axis have been associated with cutaneous malignancy, wound healing defects and inflammatory skin conditions. These collective observations suggest that the Eph/ephrin cell-cell communication pathway may be amenable to therapeutic intervention for the purpose of restoring epidermal tissue homeostasis and integrity in dermatological disorders. PMID- 22040911 TI - Ephs and ephrins in cancer: ephrin-A1 signalling. AB - Ephrin-A1 and its primary receptor, EphA2, are involved in numerous physiological processes and have been intensely studied for their roles in malignancy. Ephrin Eph signalling is complex on its own and is also cell-type dependent, making elucidation of the exact role of ephrin-A1 in neoplasia challenging. Multiple oncogenic signalling pathways, such as MAP/ERK and PI3K are affected by ephrin A1, and in some cases evidence suggests the promotion of a specific pathway in one cell or cancer type and inhibition of the same pathway in another type of cell or cancer. Ephrin-A1 also plays an integral role in angiogenesis and tumor neovascularization. Until recently, studies investigating ephrins focused on the ligands as GPI-anchored proteins that required membrane anchoring or artificial clustering for Eph receptor activation. However, recent studies have demonstrated a functional role for soluble, monomeric ephrin-A1. This review will focus on various forms of ephrin-A1-specific signalling in human malignancy. PMID- 22040913 TI - Axonal ephrinA/EphA interactions, and the emergence of order in topographic projections. AB - In the classical view of axon guidance, neurons send out axons which are endowed with guidance receptors enabling them to find their (distant) target areas by an interaction with their ligands expressed in specific spatio-temporal patterns along their pathways and in their target area. However, this view has recently been confounded by more detailed analyses of, for example, the expression patterns of EphAs and ephrinAs in the retinotectal projection. Here ephrinA 'ligands' are expressed not only in the target area but also on the projecting RGC axons, and EphA 'receptors' not only on retinal ganglion cell (RGC) axons but also in the target area itself. This review describes the on-going functional characterisation of the surprising co-expression of ephrinAs and EphAs on retinal ganglion cell (RGC) axons and other cell types. It also investigates the function of ephrinAs as receptors and describes their interaction with co-receptors involved in mediating this function. PMID- 22040912 TI - Clinical relevance of Ephs and ephrins in cancer: lessons from breast, colorectal, and lung cancer profiling. AB - Pre-clinical studies provide compelling evidence that members of the Eph family of receptor tyrosine kinases and their ephrin ligands promote tumor growth, invasion and metastasis, and neovascularization. Tumor suppressive roles have also been reported for the receptors, and ligand-dependent versus ligand independent signaling has emerged as one key mechanism underlying tumor suppressive function as opposed to oncogenic effects. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. Expression profiling in human patient samples bridges this gap and provides valuable clinical relevance to laboratory observations. In addition to analyses performed using privately assembled patient tumor samples, publically available microarray datasets and tissue microarrays linked to clinical data have emerged as tractable tools for addressing the clinical relevance of specific molecules and families of related molecules. This review summarizes the clinical relevance of specific Eph and ephrin molecules in human breast, colorectal, and lung cancers. PMID- 22040914 TI - Non-SH2/PDZ reverse signaling by ephrins. AB - Great strides have been made regarding our understanding of the processes and signaling events influenced by Eph/ephrin signaling that play a role in cell adhesion and cell movement. However, the precise mechanisms by which these signaling events regulate cell and tissue architecture still need further resolution. The Eph/ephrin signaling pathways and the ability to regulate cell cell adhesion and motility constitutes an impressive system for regulating tissue separation and morphogenesis (Pasquale, 2005, 2008 [1,2]). Moreover, the de regulation of this signaling system is linked to the promotion of aggressive and metastatic tumors in humans [2]. In the following section, we discuss some of the interesting mechanisms by which ephrins can signal through their own intracellular domains (reverse signaling) either independent of forward signaling or in addition to forward signaling through a cognate receptor. In this review we discuss how ephrins (Eph ligands) "reverse signal" through their intracellular domains to affect cell adhesion and movement, but the focus is on modes of action that are independent of SH2 and PDZ interactions. PMID- 22040916 TI - Eph and ephrin signaling: lessons learned from spinal motor neurons. AB - In nervous system assembly, Eph/ephrin signaling mediates many axon guidance events that shape the formation of precise neuronal connections. However, due to the complexity of interactions between Ephs and ephrins, the molecular logic of their action is still being unraveled. Considerable advances have been made by studying the innervation of the limb by spinal motor neurons, a series of events governed by Eph/ephrin signaling. Here, we discuss the contributions of different Eph/ephrin modes of interaction, downstream signaling and electrical activity, and how these systems may interact both with each other and with other guidance molecules in limb muscle innervation. This simple model system has emerged as a very powerful tool to study this set of molecules, and will continue to be so by virtue of its simplicity, accessibility and the wealth of pioneering cellular studies. PMID- 22040915 TI - EphA receptor signaling--complexity and emerging themes. AB - The impact of Eph and ephrin signaling on cell behavior is complex and highly context dependent. Forward signaling initiated by Eph receptor activation and reverse signaling initiated by ephrin activation often mediate opposite effects. The apparent ligand-independent functions of Eph receptors recognized recently add another layer of complexity. This review will attempt to sort out the information generated recently on signaling by the A subfamily of Eph receptors and ephrin ligands. We will focus on EphA/ephrin-A signaling in the context of several physiological and disease processes, where new progresses have been made lately and unifying themes are emerging amid previous confusions. For more comprehensive survey of literature on Eph/ephrin signaling pathways and networks, readers are referred to outstanding reviews both in this volume and in other recent publications. PMID- 22040917 TI - Looking forward to EphB signaling in synapses. AB - Eph receptors and their ligands ephrins comprise a complex signaling system with diverse functions that span a wide range of tissues and developmental stages. The variety of Eph receptor functions stems from their ability to mediate bidirectional signaling through trans-cellular Eph/ephrin interactions. Initially thought to act by directing repulsion between cells, Ephs have also been demonstrated to induce and maintain cell adhesive responses at excitatory synapses in the central nervous system. EphB receptors are essential to the development and maintenance of dendritic spines, which accommodate the postsynaptic sites of most glutamatergic excitatory synapses in the brain. Functions of EphB receptors are not limited to control of the actin cytoskeleton in dendritic spines, as EphB receptors are also involved in the formation of functional synaptic specializations through the regulation of glutamate receptor trafficking and functions. In addition, EphB receptors have recently been linked to the pathophysiology of Alzheimer's disease and neuropathic pain, thus becoming promising targets for therapeutic interventions. In this review, we discuss recent findings on EphB receptor functions in synapses, as well as the mechanisms of bidirectional trans-synaptic ephrin-B/EphB receptor signaling that shape dendritic spines and influence post-synaptic differentiation. PMID- 22040918 TI - Eph/ephrin signaling: genetic, phosphoproteomic, and transcriptomic approaches. AB - The Eph receptor tyrosine kinases and their ephrin partners compose a large and complex family of signaling molecules involved in a wide variety of processes in development, homeostasis, and disease. The complexity inherent to Eph/ephrin signaling derives from several characteristics of the family. First, the large size and functional redundancy/compensation by family members presents a challenge in defining their in vivo roles. Second, the capacity for bidirectional signaling doubles the potential complexity, since every member has the ability to act both as a ligand and a receptor. Third, Ephs and ephrins can utilize a wide array of signal transduction pathways with a tremendous diversity of cell biological effect. The daunting complexity of Eph/ephrin signaling has increasingly prompted investigators to resort to multiple technological approaches to gain mechanistic insight. Here we review recent progress in the use of advanced mouse genetics in combination with proteomic and transcriptomic approaches to gain a more complete understanding of signaling mechanism in vivo. Integrating insights from such disparate approaches provides advantages in continuing to advance our understanding of how this multifarious group of signaling molecules functions in a diverse array of biological contexts. PMID- 22040919 TI - Biochemical and pharmacological profile of darexaban, an oral direct factor Xa inhibitor. AB - Darexaban (YM150) is an oral factor Xa inhibitor developed for the prophylaxis of venous and arterial thromboembolic disease. This study was conducted to investigate the biochemical and pharmacological profiles of darexaban and its active metabolite darexaban glucuronide (YM-222714), which predominantly determines the antithrombotic effect after oral administration of darexaban. In vitro activity was evaluated by enzyme and coagulation assays, and a prothrombin activation assay using reconstituted prothrombinase or whole blood clot. In vivo effects were examined in venous thrombosis, arterio-venous (A-V) shunt thrombosis, and bleeding models in rats. Both darexaban and darexaban glucuronide competitively and selectively inhibited human factor Xa with Ki values of 0.031 and 0.020 MUM, respectively. They showed anticoagulant activity in human plasma, with doubling concentrations of darexaban and darexaban glucuronide for prothrombin time of 1.2 and 0.95 MUM, respectively. Anticoagulant activity was independent of antithrombin. Darexaban and darexaban glucuronide inhibited the prothrombin activation induced by prothrombinase complex or whole blood clot with similar potency to free factor Xa. In contrast, prothrombinase- and clot-induced prothrombin activation were resistant to inhibition by enoxaparin. In venous and A-V shunt thrombosis models in rats, darexaban strongly suppressed thrombus formation without affecting bleeding time, with ID50 values of 0.97 and 16.7 mg/kg, respectively. Warfarin also suppressed thrombus formation in these models, but caused a marked prolongation of bleeding time at antithrombotic dose. In conclusion, darexaban is a selective and direct factor Xa inhibitor and a promising oral anticoagulant for the prophylaxis and treatment of thromboembolic diseases. PMID- 22040920 TI - Comparative effects of high and low-dose simvastatin on prostate epithelial cells: the role of LDL. AB - Epidemiological studies have linked statin use with a decreased risk of advanced prostate cancer and an improved recurrence-free survival after radical therapy. It is unclear, however, whether statins could have direct effects against prostate cancer in a clinical setting, as their growth-inhibiting effects on prostate cancer cells have been demonstrated at drug concentrations which exceed the level in plasma during standard clinical dosing. We compared responses to high-dose and therapeutic-dose simvastatin in normal and cancerous prostate epithelial cells. Simvastatin was more effective at inhibiting the growth of normal prostate epithelial cells than of cancer cells. At therapeutic 100 nM concentration simvastatin had a cytostatic effect on normal cells: apoptosis was only slightly induced, but a decrease in cell cycle activity and an increase in senescence were observed. At therapeutic concentrations, lipophilic simvastatin caused a stronger growth inhibition than did hydrophilic rosuvastatin. In contrast, 10 MUM simvastatin had a cytotoxic effect both on normal and cancer cells. Addition of LDL-cholesterol effectively reversed the cytostatic effect in all cell lines, but overcoming the cytotoxicity of 10 MUM simvastatin required a combination of LDL-cholesterol and mevalonate. As LDL-cholesterol completely prevented the growth-inhibiting effect of therapeutic-dose simvastatin already at low, subphysiological concentrations it is unlikely that statins have direct effects on growth of prostate epithelial cells in vivo. Statins' possible benefits against prostate cancer could be due to systemic cholesterol-lowering, as suggested by epidemiological studies. Future clinical studies evaluating the effects of statins on prostate cancer prevention should monitor serum LDL and should probably administer statins at higher concentrations than those currently used in the treatment of hypercholesterolemia. PMID- 22040921 TI - Agomelatine suppresses locomotor hyperactivity in olfactory bulbectomised rats: a comparison to melatonin and to the 5-HT(2c) antagonist, S32006. AB - The novel melatonergic agonist/5-HT(2C) antagonist agomelatine displays robust antidepressant properties in humans and is active in pre-clinical models predictive of antidepressant effects. In this study, we investigated its potential influence on the locomotor hyperactivity displayed by olfactory bulbectomised rats, a putative measure of potential antidepressant activity. In addition, we compared the actions of agomelatine to those of melatonin and S32006, a selective antagonist at 5-HT(2C) receptors. Vehicle, agomelatine (10 and 50mg/kg), melatonin (10 and 50mg/kg), S32006 (0.16mg/kg to 10mg/kg) and the prototypical tricyclic antidepressant, imipramine (10mg/kg), were administered by intraperitoneal injection for 14days to male, Sprague-Dawley sham-operated and bulbectomised rats. In agreement with previous studies, imipramine was active in the model and both the lower and higher doses of agomelatine also significantly and markedly reversed the bulbectomy-induced hyperactivity to a level comparable to that seen in sham operated animals, in which agomelatine exerted no effect. Similarly the 5-HT(2C) antagonist, S32006, dose-dependently and significantly attenuated hyperactivity of bulbectomised animals, albeit with a maximal effect somewhat less marked than that of agomelatine. On the other hand, melatonin did not affect the locomotor behaviour of bulbectomised rats. The activity of agomelatine in the model is consistent with its known antidepressant properties in the clinic. PMID- 22040922 TI - Tangeretin, a citrus flavonoid, inhibits PGDF-BB-induced proliferation and migration of aortic smooth muscle cells by blocking AKT activation. AB - Tangeretin, a natural polymethoxylated flavone concentrated in the peel of citrus fruits, is known to have antiproliferative, antiinvasive, antimetastatic and antioxidant activities. However, the effect of tangeretin on vascular smooth muscle cells (VSMCs) is unknown. This study examined the effect of tangeretin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of rat aortic smooth muscle cells (RASMCs) as well as its underlying mechanisms. Tangeretin significantly inhibited proliferation, DNA synthesis and migration of PDGF-BB-stimulated RASMCs without inducing cell death. Treatment with tangeretin induced cell-cycle arrest in the G0/G1 phase was associated with down-regulation of cyclin D1 and cyclin E in addition to up-regulation of p27(kip1). We also showed that tangeretin inhibited PDGF-BB-induced phosphorylation of AKT, while it had no effect on the phosphorylation of phospholipase Cgamma (PLCgamma), PDGF receptor beta-chain (PDGF-Rbeta) and extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs). An in vitro kinase assay revealed that tangeretin inhibited AKT activity in a dose-dependent manner. Moreover, treatment of LY294002, a phosphoinositide 3 kinase (PI3K) inhibitor, had similar effects than that of tangeretin on the expression of p27(kip1) and cyclin D1, as well as cell migration in PDFG-BB stimulated RASMCs. Taken together, these findings suggest that tangeretin could suppress PDGF-BB-induced proliferation and migration of RASMCs through the suppression of PI3K/AKT signaling pathway, and may be a potential candidate for preventing or treating vascular diseases, such as atherosclerosis and restenosis. PMID- 22040923 TI - Noradrenaline contracts rat retinal arterioles via stimulation of alpha(1A)- and alpha(1D)-adrenoceptors. AB - The aim of this study was to characterize the alpha1-adrenoceptor subtype(s) involved in the noradrenaline-induced contraction of retinal arterioles in rats. In vivo ocular fundus images were captured with a digital camera equipped with a special objective lens. By measuring changes in diameter of retinal arterioles in the fundus images, retinal vascular response was assessed. The systemic blood pressure and heart rate in the animals were also continuously recorded. Following blockade of beta1/beta2-adrenoceptors with propranolol, noradrenaline (0.03-3 MUg/kg/min, i.v.) decreased the diameter of retinal arterioles and increased the mean blood pressure in a dose-dependent manner. The highest dose (3 MUg/kg/min, i.v.) of noradrenaline caused a small increase in heart rate. The alpha(1A) adrenoceptor antagonist RS100329 (0.1 mg/kg, i.v.) and the alpha(1D)-adrenoceptor antagonist BMY 7378 (1 mg/kg, i.v.) significantly prevented noradrenaline-induced contraction of retinal arterioles and pressor responses whereas the alpha(1B) adrenoceptor antagonist L-765314 (1 mg/kg, i.v.) did not. The alpha(1A) adrenoceptor agonist, A 61603 (0.03-0.3 MUg/kg/min, i.v.), also caused contractile responses of retinal arterioles and pressor responses. These responses were almost completely prevented by RS100329 (0.1 mg/kg, i.v.), but not by BMY 7378 (1 mg/kg, i.v.). These results suggest that the contractile effects of noradrenaline on retinal arterioles and peripheral resistance vessels are, at least in part, mediated by stimulation of alpha(1A)- and alpha(1D)-adrenoceptors. Furthermore, it is likely that the alpha1-adrenoceptor subtype(s) involved in rat vascular responses are similar in both retinal and peripheral circulation. PMID- 22040924 TI - Galactomannan detection in bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in patients with hematological diseases-the role of factors affecting assay performance. AB - BACKGROUND: We evaluated the performance of a galactomannan (GM) assay in bronchoalveolar lavage (BAL) fluid compared to serum samples for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematological diseases. METHODS: Two hundred and fifty-five bronchoscopies were performed on 230 patients. Bronchial and alveolar samples from BAL fluid as well as serum samples were analyzed in the GM assay. RESULTS: Twenty-eight cases of IPA (11%) were diagnosed. The sensitivity, specificity, positive predictive value, and negative predictive value of the GM assay using a cut-off of 0.5 were 57.1%, 99.3%, 94.1%, and 92.5%, respectively, for the alveolar sample; 44.0%, 99.3%, 91.7%, and 91.4%, respectively, for the bronchial sample; and 60.7%, 100%, 100%, and 92.9%, respectively, for serum. The highest sensitivity (78.6%) with good specificity (98.6%) was obtained with a 'triple detection' of GM in bronchial, alveolar, and serum samples. Neutropenia and antifungal therapy for only 24h increased the sensitivity, while antifungal treatment for >= 2 days decreased assay performance. Moreover, a trend towards a higher volume of aspirated fluid in GM negative BAL (p=0.092) was observed. CONCLUSIONS: In contrast to recently published data, we found only moderate sensitivity, but high specificity and high positive predictive value of the detection of GM in BAL fluid. In addition, neutropenia, antifungal therapy, and BAL standardization affected GM assay performance. PMID- 22040926 TI - Serum 25-hydroxyvitamin D and muscle atrophy in the elderly. AB - The objective of this review is to consider the mechanisms by which vitamin D affects muscle and the evidence that vitamin D status is important for muscle performance and fall prevention in older adults. Vitamin D receptors have been identified in human skeletal-muscle cells. Activation of these receptors by 1,25 dihydroxyvitamin D is involved in the action of vitamin D on the myocyte. Several studies have examined the effect of supplemental vitamin D on muscle strength, balance and falls. Among those examining muscle strength, results have been either positive for vitamin D or null. A recent meta-analysis of seventeen such trials revealed no significant effect of vitamin D overall, but a significant improvement in strength was observed in the trials in which the mean starting level of 25-hydroxyvitamin D was 25 nmol/l or below. Evidence for an effect of vitamin D on balance, measured as sway, is less abundant but more consistently positive. Many trials have evaluated the effect of supplemental vitamin D on falls. Overall, there is about a 20% lower risk of falling with supplementation. One meta-analysis considered the vitamin D dose administered and concluded that doses up through 15 MUg (600 IU) were ineffective and doses of 17.5-25 MUg/d (700 1000 IU/d) significantly lowered fall risk. The minimal 25-hydroxyvitamin D level needed for benefit was 60 nmol/l. PMID- 22040925 TI - Skin colonization by superantigen-producing Staphylococcus aureus in Egyptian patients with atopic dermatitis and its relation to disease severity and serum interleukin-4 level. AB - OBJECTIVE: The objective of the current study was to detect Staphylococcus aureus colonization and the presence of superantigen in atopic dermatitis (AD) in Egyptian patients, and to determine its effect on disease severity and serum interleukin (IL)-4 levels. METHODS: Swabs were taken from the skin of 30 patients with AD. S. aureus isolates were screened for the presence of genes of exotoxins with superantigen properties by multiplex PCR. Serum IL-4 was determined by ELISA. The rate of S. aureus colonization and the presence of superantigen were correlated with disease severity and IL-4 level. RESULTS: Twenty-six of 30 patients (87%) were colonized by S. aureus, and 14 of the 26 (54%) patients were colonized with toxigenic strains. The most frequent superantigen gene present in S. aureus isolates was that coding for staphylococcal enterotoxin B (SEB), followed by both staphylococcal enterotoxin C (SEC) and toxic shock syndrome toxin-1 (TSST-1) genes. The mean 'severity scoring in AD' (SCORAD) score of AD patients colonized with S. aureus harboring superantigen genes (74 +/- 8) was significantly higher than that in those colonized with S. aureus isolates without superantigen genes (56 +/- 6) (p<0.001). Serum IL-4 levels followed the same pattern. CONCLUSIONS: S. aureus may play an important role as an aggravating factor in AD patients. Reducing the colonization of atopic skin by S. aureus is therefore the best way to reduce superantigen-induced allergic skin inflammation. PMID- 22040927 TI - Do current criteria for 'healthy BMI' in adolescence warrant a re-think? PMID- 22040928 TI - Incidence of early burn-induced effects on liver function as reflected by the plasma disappearance rate of indocyanine green: a prospective descriptive cohort study. AB - Organ dysfunction and failure are important for burned patients as they increase morbidity and mortality. Recent evidence has suggested that organ injuries are occurring earlier after burns, and are more common than previously thought. In this study we have assessed the extent to which liver function, assessed by the plasma disappearance rate of indocyanine green (PDR(ICG)), is affected in patients with severe burns. This is a prospective, descriptive exploratory study at a national burn centre. Consecutive adult patients with a percent total body surface area burned (TBSA%) of 20% or more, were examined prospectively by dynamic (PDR(ICG)) and static liver function tests (plasma: bilirubin concentration, prothrombin complex, and alanine aminotransferase and alkaline phosphatase activities). Early liver dysfunction was common, as it is assessed by both dynamic (7 of 17) and static liver function tests (6-17 of 17). A regression model showed that changes in PDR(ICG) were associated with age, TBSA%, plasma bilirubin concentration, plasma C-reactive protein concentration, and cardiac index. Persistent and advanced hepatic dysfunction was associated with mortality. The PDR(ICG) seems to give a comprehensive assessment of liver function after major burns. Hepatic dysfunction seems to be as common as dysfunction in other organs. We interpret the recorded effects on liver function as part of a multiple organ dysfunction syndrome, primarily induced by the burn itself. However, this needs to be further investigated. PMID- 22040929 TI - Burns, inhalation injury and ventilator-associated pneumonia: value of routine surveillance cultures. AB - PURPOSE: Burn patients with inhalation injury are at particular risk for ventilator-associated pneumonia (VAP). Routine endotracheal surveillance cultures may provide information about the causative pathogen in subsequent VAP, improving antibiotic therapy. Our objective was to assess the incidence of VAP in burn patients with inhalation injury, and the benefit of routine surveillance cultures to predict multidrug resistant (MDR) pathogens. PROCEDURES: Historical cohort (n=53) including all burn patients with inhalation injury requiring mechanical ventilation, admitted to the Ghent burn unit (2002-2010). MAIN FINDINGS: Median (interquartile range) age and total burned surface area were 44y (39-55y) and 35% (19-50%). Overall, 70 episodes of VAP occurred in 46 patients (86.8%). Median mechanical ventilation days (MVD) prior to VAP onset were 7d (4-9d). The incidence was 55 episodes/1000 MVD. In 23 episodes (32.9%) at least one MDR causative pathogen was involved, mostly Pseudomonas aeruginosa and Enterobacter spp. The sensitivity and specificity of surveillance cultures to predict MDR etiology in subsequent VAP was respectively 83.0% and 96.2%. The positive and negative predictive value was 87.0% and 95.0%, respectively. CONCLUSIONS: The incidence of VAP in burn patients with inhalation injury is high. In this cohort routine surveillance cultures had excellent operating characteristics to predict MDR pathogen involvement. PMID- 22040930 TI - A high prevalence of mupirocin and macrolide resistance determinant among Staphylococcus aureus strains isolated from burnt patients. AB - Infections due to Staphylococcus aureus have become increasingly common among burn patients. The antibiotic resistance profile of S. aureus isolates and inducible resistance against clindamycin were investigated in this study. The presence of mecA gene, mupA gene and macrolide resistance genes were detected using PCR and multiplex-PCR. The resistance rate to methicillin, erythromycin and mupirocin were 58.5%, 58% and 40%, respectively. The prevalence of constitutive and inducible resistance among macrolide resistant isolates was 75% and 25%, respectively. Ninety five percent of the isolates were positive for one or more erm genes. The most common genes were ermA (75%), ermC (72%) and ermB (69%), respectively. The ermA gene predominated in the strains with the inducible phenotype, while ermC was more common in the isolates with the constitutive phenotype. The msrA gene was only found in one MRSA isolate with the constitutive phenotype. A total of 27 isolates (25%) carried the mupA gene. All the mupirocin resistant isolates and almost all the erythromycin resistant isolates were also resistant against methicillin which may indicate an outbreak of MRSA isolates with high-level mupirocin and erythromycin resistance in the burn unit assessed. PMID- 22040931 TI - Evaluation of long term health-related quality of life in extensive burns: a 12 year experience in a burn center. AB - OBJECTIVES: We sought to evaluate the long term health-related quality of life (HRQOL) in patients survived severely extensive burn and identify their clinical predicting factors correlated with HRQOL. METHODS: A cross-sectional study was conducted in 20 patients survived more than 2 years with extensive burn involving >=70% total body surface area (TBSA) between 1997 and 2009 in a burn center in Shanghai. Short Form-36 Medical Outcomes Survey (SF-36), Brief Version of Burn Specific Health Scale (BSHS-B) and Michigan Hand Outcome Questionnaire (MHQ) were used for the present evaluation. SF-36 scores were compared with a healthy Chinese population, and linear correlation analysis was performed to screen the clinical relating factors predicting physical and mental component summary (PCS and MCS) scores from SF-36. RESULTS: HRQOL scores from SF-36 were significantly lower in the domains of physical functioning, role limitations due to physical problems, pain, social functioning and role limitations due to emotional problems compared with population norms. Multiple linear regression analysis demonstrated that only return to work (RTW) predicted improved PCS. While age at injury, facial burns, skin grafting and length of hospital stay were correlated with MCS. Work, body image and heat sensitivity obtained the lowest BSHS-B scores in all 9 domains. Improvements of HRQOL could still be seen in BSHS-B scores in domains of simple abilities, hand function, work and affect even after a quite long interval between burns and testing. Hand function of extensive burn patients obtained relatively poor MHQ scores, especially in those without RTW. CONCLUSIONS: Patients with extensive burns have a poorer quality of life compared with that of general population. Relatively poor physical and psychological problems still exist even after a long period. Meanwhile, a trend of gradual improvements was noted. This information will aid clinicians in decision-making of comprehensive systematic regimens for long term rehabilitation and psychosocial treatment. PMID- 22040932 TI - Enhanced secretion of TIMP-1 by human hypertrophic scar keratinocytes could contribute to fibrosis. AB - Hypertrophic scars are a pathological process characterized by an excessive deposition of extracellular matrix components. Using a tissue-engineered reconstructed human skin (RHS) method, we previously reported that pathological keratinocytes induce formation of a fibrotic dermal matrix. We further investigated keratinocyte action using conditioned media. Results showed that conditioned media induce a similar action on dermal thickness similar to when an epidermis is present. Using a two-dimensional electrophoresis technique, we then compared conditioned media from normal or hypertrophic scar keratinocytes and determined that TIMP-1 was increased in conditioned media from hypertrophic scar keratinocytes. This differential profile was confirmed using ELISA, assaying TIMP 1 presence on media from monolayer cultured keratinocytes and from RHS. The dermal matrix of these RHS was recreated using mesenchymal cells from three different origins (skin, wound and hypertrophic scar). The effect of increased TIMP-1 levels on dermal fibrosis was also validated independently from the mesenchymal cell origin. Immunodetection of TIMP-1 showed that this protein was increased in the epidermis of hypertrophic scar biopsies. The findings of this study represent an important advance in understanding the role of keratinocytes as a direct potent modulator for matrix degradation and scar tissue remodeling, possibly through inactivation of MMPs. PMID- 22040933 TI - The use of lignocaine gel as a shaving gel for facial burns. PMID- 22040934 TI - Time and regeneration in burns treatment: heading into the first worldwide clinical trial with cadaveric mesenchymal stem cells. PMID- 22040935 TI - Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice. AB - BACKGROUND: Lutein is an important eye-protective nutrient. This study investigates the protective effects and mechanisms of lutein on lipopolysaccharides (LPS)-induced uveitis in mice. METHODS: Lutein, suspended in drinking water at a final concentration of 12.5 and 25 mg/mL, was administered to mice at 0.1 mL/10 g body weight for five consecutive days. Control and model group received drinking water only. Uveitis was induced by injecting LPS (100 mg per mouse) into the footpad in the model and lutein groups on day 5 after the last drug administration. Eyes of the mice were collected 24 hours after the LPS injection for the detection of indicators using commercial kits and reverse transcription-polymerase chain reaction. RESULTS: LPS-induced uveitis was confirmed by significant pathological damage and increased the nitric oxide level in eye tissue of BALB/C mice 24 hours after the footpad injection. The elevated nitric oxide level was significantly reduced by oral administration of lutein (125 and 500 mg/kg/d for five days) before LPS injection. Moreover, lutein decreased the malondialdehyde content, increased the oxygen radical absorbance capacity level, glutathione, the vitamin C contents and total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Lutein further increased expressions of copper-zinc SOD, manganese SOD and GPx mRNA. Conclusion The antioxidant properties of lutein contribute to the protection against LPS induced uveitis, partially through the intervention of inflammation process. PMID- 22040936 TI - Three-year follow-up of sirolimus-eluting stents vs. bare metal stents for acute myocardial infarction. AB - BACKGROUND: The long-term safety and efficacy of drug-eluting stents for patients with acute myocardial infarction (AMI) remain controversial. METHODS AND RESULTS: A total of 143 consecutive patients who presented between August 2004 and July 2006 with AMI and who underwent primary percutaneous coronary intervention (PCI) using sirolimus-eluting stents (SES), were compared with a historical control cohort of 129 consecutive patients who presented between August 2002 and July 2004 and who underwent primary PCI using bare metal stents (BMS). The rate of major adverse cardiovascular events at 3 years was significantly lower in the SES group than in the BMS group (20.3% vs. 33.1%, respectively; P=0.01). This reduction was mainly driven by a decrease in the rate of target vessel revascularization (12.3% vs. 22.4%, respectively; P=0.02). There was no significant difference in the rate of cardiovascular death (4.5% vs. 5.7%, respectively; P=0.67), non-fatal myocardial infarction (4.5% vs. 9.2%, respectively; P=0.16), coronary artery bypass grafting (2.3% vs. 2.5%, respectively; P=0.93), stroke (2.4% vs. 0.8%, respectively; P=0.35), and stent thrombosis (2.9% vs. 2.3%, respectively; P=0.80) between the 2 groups. CONCLUSIONS: SES can be used safely and effectively in patients with AMI. PMID- 22040937 TI - Medetomidine, an alpha(2)-adrenergic agonist, activates cardiac vagal nerve through modulation of baroreflex control. AB - BACKGROUND: Although alpha(2)-adrenergic agonists have been reported to induce a vagal-dominant condition through suppression of sympathetic nerve activity, there is little direct evidence that they directly increase cardiac vagal nerve activity. Using a cardiac microdialysis technique, we investigated the effects of medetomidine, an alpha(2)-adrenergic agonist, on norepinephrine (NE) and acetylcholine (ACh) release from cardiac nerve endings. METHODS AND RESULTS: A microdialysis probe was implanted into the right atrial wall near the sinoatrial node in anesthetized rabbits and perfused with Ringer's solution containing eserine. Dialysate NE and ACh concentrations were measured using high-performance liquid chromatography. Both 10 and 100ug/kg of intravenous medetomidine significantly decreased mean blood pressure (BP) and the dialysate NE concentration, but only 100ug/kg of medetomidine enhanced ACh release. Combined administration of medetomidine and phenylephrine maintained mean BP at baseline level, and augmented the medetomidine-induced ACh release. When we varied the mean BP using intravenous administration of phenylephrine, treatment with medetomidine significantly steepened the slope of the regression line between mean BP and log ACh concentration. CONCLUSIONS: Medetomidine increased ACh release from cardiac vagal nerve endings and augmented baroreflex control of vagal nerve activity. PMID- 22040939 TI - Clinical significance of microalbuminuria in high-risk patients with coronary artery disease. PMID- 22040938 TI - Nitroglycerin use in myocardial infarction patients. AB - Acute myocardial infarction (MI) and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin (glyceryl trinitrate [GTN]) remains a first-line treatment for angina pectoris and acute MI. Nitroglycerin achieves its benefit by giving rise to nitric oxide (NO), which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of GTN results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is caused, at least in part, by inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts GTN to the vasodilator, NO. We recently found that in a MI model in animals, in addition to GTN's effect on the vasculature, sustained treatment negatively affected cardiomyocyte viability following ischemia, thus resulting in increased infarct size. Coadministration of Alda-1, an activator of ALDH2, with GTN improves metabolism of reactive aldehyde adducts and prevents the GTN-induced increase in cardiac dysfunction following MI. In this review, we describe the molecular mechanisms associated with the benefits and risks of GTN administration in MI. PMID- 22040940 TI - Application of high-sensitivity cardiac troponin values. PMID- 22040941 TI - Tobacco or health. In the historical context of epidemiology. PMID- 22040942 TI - Continuity and change: the future for Health Services Management Research. PMID- 22040943 TI - Improving patient satisfaction in hospital care settings. AB - Health-care managers have to address many aspects of the organization, and patient satisfaction is clearly one of the critical aspects for managers. To respond to the need of health-care managers, there have been many patient satisfaction studies. However, these studies focus on which attributes (factors such as nursing care and physician care) are more influential; they do not provide specific aspects for each attribute. In order to develop an effective intervention programme to improve patient satisfaction, more specific research outcomes are needed. This study utilized data collected between January 2007 and June 2008 from 32 hospitals representing a large, national private not-for-profit hospital system. The patient satisfaction survey included the Consumer Assessment of Healthcare Providers and Systems, Hospital version questionnaire items, and there are 31,471 cases. Two-stage multiple linear regression analyses were conducted with control variables (age, gender, perceived health, education and race). It was found that patients' highest priority is to be treated with courtesy and respect by nurses and physicians. An effective intervention programme to improve patient satisfaction would include a training programme, where care providers understand that patients want them to show courtesy and respect. Then, well-trained and empathetic nurses and staff members can comfort patients, and consequently improve patient satisfaction. PMID- 22040944 TI - A study of relationship between job stress, quality of working life and turnover intention among hospital employees. AB - Job stress is a serious threat to the quality of working life (QWL) of health care employees and can cause hostility, aggression, absenteeism and turnover, as well as reduced productivity. In addition, job stress among employees affects the quality of health-care services. The purpose of this study was to gain a better understanding of the relationships between job stress and QWL of employees, and their impact on turnover intention at Isfahan hospitals, Iran. The study employed a cross-sectional research design. A validated questionnaire was used to collect data from hospital employees. Overall, 26% of employees graded their job stress high. The major sources of stress were inadequate pay, inequality at work, too much work, staff shortage, lack of recognition and promotion prospects, time pressure, lack of job security and lack of management support. An inverse relationship was found between job stress and QWL among hospital employees. The most important predictor of QWL was disturbance handling, followed by job proud, job security and job stress. Finally, while QWL was negatively associated with turnover intentions, job stress was positively related to employees' intention to quit. Since job stress has a strong correlation with employee QWL and turnover intention, it is very important to apply the right human resources policies to increase employees' QWL and decrease subsequent turnover. This study invites further research to explore, implement and evaluate intervention strategies for prevention of occupational stress and improvement in QWL. PMID- 22040945 TI - Evaluation and measurement for improvement in service-level quality improvement initiatives. AB - The National Health Service (NHS) in England, as with other health services worldwide, currently faces the need to reduce costs and to improve the quality of patient care. Evidence gathered through effective and appropriate measurement and evaluation, is essential to achieving this. Through interviews with service improvement managers and analysis of comments in a seminar of NHS staff involved in health service improvement, we found a lack of understanding regarding the definition and methodology of both measurement and evaluation, which decreases the likelihood that NHS staff will be competent to commission or provide these skills. In addition, we highlight the importance of managers assessing their organizations' 'readiness' to undergo change before embarking on a quality improvement (QI) initiative, to ensure that the initiative's impact can be adequately judged. We provide definitions of measurement for improvement and of evaluation, and propose a comparative framework from which to gauge an appropriate approach. Examples of two large-scale QI initiatives are also given, along with descriptions of some of their problems and solutions, to illustrate the use of the framework. We recommend that health service managers use the framework to determine the most appropriate approach to evaluation and measurement for improvement for their context, to ensure that their decisions are evidence based. PMID- 22040946 TI - A professional challenge: the development of skill-mix in UK primary care dentistry. AB - The future health-care workforce and the changing skill-mix within occupational teams is a current topic of discussion. This paper contributes to the skill-mix debate by focusing on UK primary care dentistry, revealing unintended as well as intended consequences of a modularized, technocratic view of dentistry. In part one, relevant literature about dental therapists and skill-mix in dentistry is organized into a framework used to review factors operating at macro, meso and micro levels. Part two considers the role that education and training may play in realizing skill-mix change. Part three synthesizes conditions required for modifying skill-mix in UK primary dental care and sets out the dimensions of seven factors: funding focus, the profession's response, workforce, the practice, dentist's knowledge, dental therapist's motivations and patient attitude. A review of these factors could be used to inform the policy decisions of managers operating at the macro level, as well as more local staffing decisions. Without consideration of the complex interplay of these factors, skill-mix in dentistry will be slow to develop and could bring unwelcome consequences. PMID- 22040947 TI - Empowering health-care managers in Australia: an action learning approach. AB - This paper reports on a training programme using action learning sets designed to enhance the management abilities of health-care managers. Numerous independent reports in Australia, and around the world, have related the lack of management systems and processes to substandard health-care delivery. This has suggested a need for better approaches to the education, training and ongoing development of health-care managers, and this paper reports on an action learning approach trialled over a three-year period. Participant managers reported significantly greater levels of empowerment and self-efficacy after participation in the year long action learning sets intervention. While too early to measure the translation of these reported individual improvements into specific management practice, the literature strongly supports more effective management practice among managers who report high levels of empowerment and self-efficacy. PMID- 22040948 TI - Well-structured teams and the buffering of hospital employees from stress. AB - Membership in well-structured teams, which show clarity in team and individual goals, meet regularly, and recognize diverse skills of their members, is known to reduce stress. This study examined how membership of well-structured teams was associated with lower levels of strain, when testing a work stressors-to-strains relationship model across the three levels of team structure, namely well structured, poorly structured (do not fulfill all the criteria of well-structured teams) and no team. The work stressors tested, were quantitative overload and hostile environment, whereas strains were measured through job satisfaction and intention to leave job. This investigation was carried out on a random sample of 65,142 respondents in acute/specialist National Health Service hospitals across the UK. Using multivariate analysis of variance, statistically significant differences between means across the three groups of team structure, with mostly moderate effect sizes, were found for the study variables. Those in well structured teams have the highest levels of job satisfaction and the least intention to leave job. Multigroup structural equation modelling confirmed the model's robustness across the three groups of team structure. Work stressors explained 45%, 50% and 65% of the variance of strains for well-structured, poorly structured and no team membership, respectively. An increase of one standard deviation in work stressors, resulted in an increase in 0.67, 0.70 and 0.81 standard deviations in strains for well-structured, poorly structured and no team membership, respectively. This investigation is an eye-opener for hospitals to work towards achieving well-structured teams, as this study shows weaker stressor to-strain relationships for members of these teams. PMID- 22040949 TI - Organizational readiness for innovation in health care: some lessons from the recent literature. AB - There is no single intervention that will trigger or ensure innovation in health care, as the interaction between the innovation and the context of its introduction is necessarily complex and variable. Although academic attention has recently turned to the role of organizations in promoting and embedding innovation, this literature remains light on prescription, and tends to ignore the issue of substitution and disengagement. Innovation needs to be adapted as well as adopted into organizational contexts and receptive climates for innovation can only be developed incrementally over time. This paper identifies recommendations for increasing the readiness of health-care organizations for innovation. Key organizational strategies for embedding innovation include: development of incentives; sophisticated knowledge management; interfunctional and interorganizational coordination and collaboration; and development of an innovation infrastructure. More attention is required to substitution and disengagement of interventions and practices (exnovation) in the current economic climate. PMID- 22040950 TI - [The role of PDGF/PDGFR in the regulation of platelet formation]. AB - Platelet-derived growth factor (PDGF), a potent chemotactic and mitogenic factor, is involved in the regulation of hematopoiesis and platelet production. Our studies demonstrate the presence of functional PDGF receptors (PDGFR) on human megakaryocytes/platelets and CD34(+) cells, and their ability to mediate a mitogenic response. PDGF promotes the ex vivo expansion of human hematopoietic stem (CD34(+)) and progenitor (CD41(+)) cells. More significantly, PDGF enhances the engraftment of human CD45(+) cells and their myeloid subsets (CD33(+), CD14(+) cells) in NOD/SCID mice. PDGF also stimulates in vitro megakaryocytopoiesis via PDGFR and/or the indirect effect on bone marrow microenvironment to produce TPO and other cytokines. It also shows a direct stimulatory effect of PDGF on c-Fos, GATA-1 and NF-E2 expressions in megakaryocytes. We speculate that these transcription factors may be involved in the signal transduction of PDGF on the regulation of megakaryocytopoiesis. PDGF also enhances platelet recovery in mouse model with radiation-induced thrombocytopenia. This radioprotective effect is likely to be mediated via PDGFR with subsequent activation of the PI3K/Akt pathway. It provides a possible explanation that blockage of PDGFR may reduce thrombopoiesis and play a role in imatinib mesylate-induced thrombocytopenia. PMID- 22040951 TI - [Resistance of leukemia KG1a cells with positive N-cadherin in phase G(0) against killing activity of VP16]. AB - Drug resistance is an important character of leukemic stem cells. To explore the mechanism of the chemotherapy resistance of N-cadherin positive leukemia cells, the quiescent state of N-cadherin positive leukemia cells was determined by flow cytometry and the relationship of G(0) phase cell ratio with the chemotherapy resistance was analyzed. After KG1a cells were induced to enter cell cycle, the G(0) phase cell ratio and the sensitivity of cells to VP16 were determined. Finally the quiescent state and drug resistance properties of KG1a cells were determined after inhibiting N-cadherin-mediated cell-cell interaction by EGTA treatment. The results showed that the G(0) phase cell ratio in N-cadherin positive KG1a cells was higher than that in N-cadherin negative KG1a cells. After KG1a cells were induced to enter cell cycle, the G(0) phase cell ratio was decreased significantly and the sensitivity of KG1a cells to VP16 increased. Following EGTA treatment for 24 hours, the G(0) phase cell ratio decreased and the drug-sensitivity was enhanced significantly. It is concluded that N-cadherin mediated adhesion keeps N-cadherin positive leukemia cells in quiescent state of G(0) phase, thus protect these leukemia cells against VP16 chemotherapy. PMID- 22040952 TI - [Silence mechanism of WT1 gene in leukemic cell line U937]. AB - This study was aimed to investigate the methylation status of WT1 gene in leukemia cell lines and its relation with expression of WT1 gene. The WT1 gene was silenced by DNA methylation or histone deacetylation, and the expression of WT1 gene was induced by using HDAC inhibitor and/or demethylation agent of DNA. Some leukemia cell lines (U937, HL-60, K562, KG1) were detected by RT-PCR, MS PCR, restriction analysis, and DNA sequencing. U937 leukemic cells without WT1 mRNA expression were incubated with HDAC inhibitor Trichostatin A (TSA) and/or demethylation agent decitabine. The results showed that the U937 cells did not express WT1 gene, but HL-60, K562 and KG1 cells highly expressed WT1 gene; WT1 gene was unmethylated in HL-60 cells, but methylated in K562 and U937 cells. WT1 expression could be reactivated by co-incubation with TSA and decitabine, but not was observed by using single drug. It is concluded that WT1 promoter is methylated in some leukemia cells, however, the methylation can not affect its expression. DNA methylation and deacetylation of histones are synergistic to inhibit the expression of WT1 in leukemic U937 cells, the combination of TSA with decitabine can induce expression of WT1 gene. PMID- 22040953 TI - [Establishment of stable subline of K562 cells expressing human leucocyte antigen a1101]. AB - The aim of this study was to establish a stable subline of K562 cells expressing the HLA-A(*)1101 protein, which was expected to provide target cells for characterizing the HLA-I restrictive antigen specific cytotoxic T lymphocyte (CTL) effects against chronic myeloid leukemia (CML). The HLA-A(*)1101 protein encoding gene was amplified from peripheral blood mononuclear cell (PBMNC) of CML patient by RT-PCR; the 2A peptide linker (D-V-E-X-N-P-G-P) gene was linked to the 3'terminal of the HLA-A(*)1101 gene by recombinant PCR, then the recombinant was cloned into the pEGFP-N3 plasmid which contains an enhanced green fluorescent protein gene, and the eukaryotic recombinant expression vector containing HLA A(*)1101-T2A-EGFP transcription box was constructed; the pEGFP-N3 vector and recombinant vector was separately electroporated into K562 cells. The expression of GFP was monitored by fluorescence microscopy, finally stably transfected sublines of K562 cells containing HLA-A(*)1101 gene, and of K562 containing pEGFP N3 vector were obtained by G418 selection; the transcriptional or translational expression of HLA-A(*)1101 gene was detected with RT-PCR and flow cytometry respectively. The results indicated that the eukaryotic expression vector HLA A(*)1101-T2A-EGFP plasmid was successfully constructed; after G418 selection for 2 months, two sublines of K562 cells (HLA-A(*)1101(+)K562, pEGFP-N3(+)K562) expressing GFP were constructed. The expression of HLA-A*A1101 gene could be determined in HLA-A(*)1101(+)K562 cell line by RT-PCR, while the pEGFP-N3(+)K562 cells could not express HLA-A*A1101 gene. HLA-A(*)1101 protein and GFP double positive HLA-A(*)1101(+)K562 cells were up to 88.5%, which was obviously higher than pEGFP-N3(+)K562 cells (0.698%) by flow cytometric analysis. It is concluded that a simple and effective method to select HLA-A(*)1101(+)K562 cells has been established and a subline of K562 cell expressing HLA-A(*)1101 protein on its cell membrane was successfully constructed, which provides the tool cells for further studying the specific cellular immunity against-CML. PMID- 22040954 TI - [Effect of homoharringtonine combined with AG490 on JAK2-STAT5 associated signal pathway in HEL cells]. AB - This study was aimed to explore the effect of homoharringtonine in combination with AG490 on JAK2-STAT5 associated signal pathway in HEL cells, and analyze its mechanism so as to provide theoretical basis for therapy of chronic myeloproliferative neoplasma by new program. The cell survival rates were tested by MTT, apoptosis was tested by flow cytometry after HEL cells were treated by 20 ng/ml HHT, 100 umol/L AG490 and 20 ng/ml HHT in combination with 100 umol/L AG490, while the signal proteins such as P-JAK2, P-STAT5 and BCL-xL activated by abnormal activated JAK2 were tested by Western blot. The results showed that both HHT and AG490 could inhabit the HEL cell proliferation after being treated for 24 hours, and Annexin V-PI double staining confirmed early apoptosis while HHT effect was more obvious, Western blot showed that the expressions of P-JAK2 and P STAT5 were down-regulated, while the total protein levels of JAK2 and STAT5 were stable. It is concluded that HHT combined with AG490 can obviously inhibit the proliferation and induce early apoptosis of HEL cells, and there is synergistic effect between the two drugs. HHT possibly acts as a broad-spectrum PTK inhibitor and synergistically with AG490 inhibits the phosphorylation of signal proteins caused by JAK2V617F, thus down-regulating the transcription of STAT5. PMID- 22040955 TI - [Effects of emodin on human erythroleukemia cell line HEL]. AB - This study was aimed to investigate the inhibitory effect of emodin on the proliferation of HEL cells, the inducing apoptosis effect of HEL cells and their mechanisms. The proliferation inhibition was detected by MTT method; the change of morphology was observed by AO/EB stains; the cell cycle and apoptosis was analyzed by flow cytometry; the expressions of Akt, P-Akt, P-GSK3beta and HSP70 proteins were determined by Western blot. The results indicated that emodin displayed significant anti-proliferative effect on HEL cells in a dose dependent manner(r = 0.99), with IC(50) value of 4.19 umol/L; AO/EB stains showed that the morphology of HEL cells obviously changed after emodin treatment for 24 hours, and at 24 and 48 hours the apoptosis rates of HEL cells treated by emodin were (27.35 +/- 1.68)% and (58.49 +/- 1.55)% respectively. Compared with blank control group, the cell ratio in G(0)/G(1) phase increased while that in S phase decreased (p < 0.01); the expression of Akt protein was not changed (p > 0.05), and that of P-Akt, P-GSK3beta and HSP70 proteins were down-regulated (p < 0.05). It is concluded that emodin efficiently inhibits the HEL cell proliferation and induces apoptosis of HEL cells, which may be related to the down-regulation of P Akt, P-GSK3beta and HSP70 proteins expression. PMID- 22040956 TI - [Effect of APN/CD13 on bestatin enhancing all-trans-retinoic acid-inducing differentiation in NB4 cells]. AB - This study was purposed to investigate the effect of aminopeptidase N/CD13 on bestatin enhancing all-trans-retinoic acid (ATRA)-inducing differentiation in NB4 cells. The nitroblue-tetrazolium (NBT) reduction assay was performed to determine the differentiation of NB4 cells, MR2 cells and primary APL blasts. The expression of P38 MAPK protein and the phosphorylation of P38 MAPK protein in NB4, MR2 and K562 cells were detected by Western blot. The results showed that pre-incubation with 5 ug/ml WM-15 blocked the enhancement effect of bestatin on differentiation of NB4 cells induced by ATRA. 5 ug/ml CD13 antibody WM-15 partly blocked the inhibition of bestatin on the phosphorylation of P38 MAPK in NB4 cells. 100 ug/ml bestatin inhibited the phosphorylation of P38 MAPK in NB4 cells and MR2 cells in a time-dependent manner. 100 ug/ml bestatin had no effect on the phosphorylation of P38 MAPK in K562 cells with low level of CD13. Bestatin could not restore the sensitivity to ATRA in ATRA-resistant primary APL blasts and MR2 cells. It is concluded that aminopeptidase N/CD13 inhibitor bestatin may enhance the differentiation-inducing activity of ATRA through inhibiting the phosphorylation of P38 MAPK in NB4 cells mediated by the cell surface APN/CD13. PMID- 22040957 TI - [Expression and clinical significances of hedgehog signaling pathway in non Hodgkin's lymphoma]. AB - This study was aimed to investigate the expression and clinicopathologic significance of Gli1 and Gli2, 2 factors of Hedgehog(Hh) signaling pathway, in non-Hodgkin's lymphoma (NHL). Gli1 and Gli2 mRNA and protein in 18 cases of NHL and 10 cases of reactive lymphadenitis were amplified and identified by real-time PCR, and were assayed by immunohistochemical staining respectively. The results showed that (1) Gli1 and Gli2 mRNA in NHL group (RQ 2.05, 2.31) were expressed higher than that in reactive lymphadenitis group (RQ 0.82, 0.89). Gli1 mRNA activated level was positively related with Gli2 (r = 0.63, p < 0.01). In addition, Gli2 also positively correlated to clinical stages of NHL (p = 0.03), but the expressions of Gli1 and Gli2 mRNA had no significant correlation to B symptoms, blood beta(2)-microglobulin, age and sex. (2) The positive expression rate of Gli1 and Gli2 protein in NHL group were 80% and 68% respectively, which were extremely higher than that in reactive lymphadenitis group. Gli1 protein level was positively related with Gli2 (r = 0.62, p < 0.05). Both Gli1 and Gli2 protein expression positively correlated to clinical staging of NHL (p = 0.05, p = 0.01). It is concluded that the Gli1 and Gli2 of Hh signaling pathway have been found to higher express in patients with NHL, and have significance for clinical staging and predicting prognosis of NHL. To further investigate the role of Hh signaling pathway in NHL will contribute to elucidate the occurrence and development of NHL, and provide a favorable method for therapy of NHL. PMID- 22040958 TI - [Characteristics of T-cell lineage immunophenotype in 95 patients with acute lymphoid leukemia]. AB - The objective of this study was to investigate the immunophenotype of T-lineage acute lymphoid leukemia (T-ALL) and to find valuable immunologic markers in T-ALL diagnosis and therapy. Four-color multiparametric flow cytometry(FCM) with CD45/SSC gating was used for immunophenotyping of 95 patients with newly diagnosed T-ALL. The results demonstrated that T-ALL occurred more frequently in males younger than 30 years of age and was usually accompanied by a high WBC count and tumor mass at diagnosis. Univariate analysis showed an influence on achievement of CR1 for age (< 30 years) but not for WBC count and tumor mass. According to WHO (2008) classification of tumors of haematopoietic and lymphoid tissues, 87 patients with confirmed subtype included 27 cases of Pro-T-ALL (31.0%), 31 cases of Pre-T-ALL (35.6%), 23 cases of cortical-T-ALL (26.4%), 6 cases of medullary-T-ALL (6.9%). CD34 expression in Pro-T-ALL was significantly higher than that of Pre-T-ALL (p = 0.001). After the first chemotherapy, the complete remission rate in Pro-T-ALL was statistically lower than that of Pre-T ALL. Besides, the complete remission rate of immature T-ALL (including Pro-T-ALL and Pre-T-ALL) was also significantly lower than that in mature T-ALL (including cortical-T-ALL and medullary-T-ALL). Myeloid antigen (CD13, CD33) expression was associated with T-ALL subtype and treatment effect. While 66.7% of CD13(+) patients belonged to Pre-T-ALL, most (60.0%) of CD33(+) patients were classified into Pro-T-ALL; CD13 expression had no effect on CR1 rate whereas CD33(+) patients had worse treatment effect compared with CD33(-) groups (p = 0.001). Notably, the expression of CD117 reached up to 26.7% and the positive cases were primarily distributed in pro-T-TAll and pre-T-ALL. It is found that CD117 expression in CD34(-) group was homogeneous and CD117 expression level was less than 10% in 73.2% patients, but CD117 expression level in CD34(+) group was not homogenous, in which group the CD117 expression levels < 10%, 10% - 20% and > 20% were 44.2%, 17.3% and 38.5% respectively. As compared with CD34(-) group, the proportion of patients with CD117 expression levels < 10%, > 20% in CD34(+) group was higher, and there was significant difference between these 2 group. It is concluded that immunophenotype has great value in T-ALL diagnosis, classification as well as treatment. Flow cytometry provides access to find valuable immunologic markers for T-ALL biological research. PMID- 22040959 TI - [Characteristics and clinical significance of CD73 expression in subtypes of leukemia]. AB - The study was purposed to investigate the expression of CD73 on bone marrow nucleated cells (BMMNC) in various leukemia subtypes and its relationship with cell differentiation of leukemia. Immunocytochemistry staining and Wright-Giemsa staining of BMMNC from 75 cases of leukemia, 11 cases of myelodysplastic syndrome (MDS), 13 cases of non-leukemic patients and 9 healthy adults were performed, and the CD73(+) ratio in BMMNC and its relationship with differentiation of leukemia cells were analyzed. The results showed that the ratios of CD73(+) in BMMNC of com-B ALL, pre-B ALL and PLL were significantly higher than those in B-CLL (p < 0.05). CD73(+) ratios in AML subtypes of M(1), M(2a), t (8; 21), t (15; 17), M(4) and M(5) were markedly higher than those in MDS respectively, but in M(6) and MDS were lower and had no statistical difference between them. CD73(+) ratios in T ALL, B-CLL, M(6), MDS, non-leukemia patients and healthy adults were close to each other and all of them were lower than those in B-ALL and other AML subtypes. It is concluded that the expression of CD73 is associated with leukemia subtype, differentiation and development. The higher differentiation of leukemia cells, the lower of CD73 expression in myeloid and B lymphoid leukemia, but T-ALL does not meet this pattern. PMID- 22040960 TI - [mRNA levels detected by real-time quantitative RT-PCR in chronic lymphocytic leukemia and their clinical significance]. AB - This study was aimed to investigate the expression level of murine double minute 4 (MDM4) mRNA in chronic lymphocytic leukemia (CLL) and its prognostic value in CLL. By means of beta-actin as internal reference, the real-time quantitative RT PCR was set up. The expression of MDM4 mRNA in 66 CLL patients was measured by fluorescence dye SYBR Green I. The dispersion of MDM4 expression ratio of groups with different prognostic factors was described by using Mann-Whitney U test. The results showed that the median MDM4 mRNA expression level was 0.037098 (0.088245 0.014875) in CLL patients. The expression level of MDM4 mRNA was significantly higher in patients with P53 gene deletion than that in patients without P53 gene deletion (0.13167 vs 0.030927) (p < 0.001), and also significantly higher in patients with P53 mutation than that in patients without P53 mutation (0.13167 vs 0.03077) (p < 0.001). MDM4 expression was also associated with Binet stages (p = 0.044) and ATM gene deletion (p = 0.046), but was not associated with LDH (p = 0.216), beta(2)-MG (p = 0.314), TK1 (p = 0.300), ZAP-70 (p = 0.559), CD38 (p = 0.513) and IgVH mutation status (p = 0.333). It is concluded that the expression level of MDM4 is significantly higher in patients with P53 deletion or mutation. MDM4 expression is significantly associated with Binet stages and ATM gene deletion. MDM4 may be an important prognostic factor in CLL. PMID- 22040961 TI - [Clinical significance of leukemia stem/progenitor cell related gene expression in acute leukemia]. AB - This study was aimed to detect the expression of leukemia stem/progenitor cell (LSPC) related genes (ABCB1, BMI-1, HOXB4) in the patients with acute leukemia, and to explore its clinical significance in acute leukemia. Bone marrow samples were collected from de novo acute leukemia patients (41 cases), patients with complete remission (CR, 16 cases) and the patients with non-malignant hematologic diseases (10 cases) respectively. And the expressions of ABCB1, BMI-1, HOXB4 genes were detected by comparative real-time quantitative PCR (RQ-PCR) with SYBR Green assay. The results showed that the expressions of ABCB1, BMI-1, HOXB4 were not detected in the patients with non-malignant hematologic diseases, but were higher (relative expressive level: 4.26 +/- 2.26, 3.72 +/- 1.91, 3.74 +/- 2.38) in de novo acute leukemia patients and lower (relative expressive level: 2.14 +/- 1.47, 2.07 +/- 0.99, 1.47 +/- 0.89) in the acute leukemia patients with CR (p < 0.05). The expressions of LSPC related genes were lower (relative expressive level: 1.77 +/- 1.29, 2.09 +/- 1.26, 1.78 +/- 1.49) in the patients acquired CR/partial remission (PR) than those in the patients not acquired CR/PR (relative expressive level: 7.23 +/- 1.78, 3.96 +/- 0.92, 4.48 +/- 2.57) (p < 0.01). Univariate analysis revealed that there were more cases with the expression of LSPC immunophenotype (CD34(+)CD38(-)CD96(+) and CD34(+)CD38(-)CD123(+)) and more hyperleukocytosis cases in patients with any higher expression of LSPC related gene (p < 0.05). Analysis of multiple parameters discovered larger significance (p < 0.01). It is concluded that there is a good relationship between LSPC related genes (ABCB1, BMI-1, HOXB4) and LSPC immunophenotype. The expression of LSPC-related genes is higher in de novo acute leukemia patients, and lower in patients acquired CR/PR. The patients with higher expressed LSPC-related genes display worse response to chemotherapy, lower CR/PR rate and higher leukocytosis, the analysis of multiple parameters may be a good method for assessing the therapeutic efficacy/prognosis of acute leukemia. PMID- 22040962 TI - [Clinical value of interphase fluorescent in situ hybridization in diagnosis of core-binding factor acute myelocytic leukemia]. AB - The purpose of this study was to evaluate the clinical value of interphase fluorescence in situ hybridization (I-FISH) in diagnosis of core-binding factor acute myelocytic leukemia (CBF AML). The cytogenetic characteristics in leukemia cells from 82 cases of AML-M(2) and 43 cases of AML-M(4)/M(5) were detected by using I-FISH with AML1-ETO double color double fusion probe and double color break point isolated gene probe CBFbeta-MYH11, and the detected results were compared with results detected by conventional cytogenetic R banding technique (CC). The results indicated that AML1-ETO fusion gene was detected in 30.5% cases (25/82) by FISH, and t(8;21)(q22;q22) karyotypic aberrations was found in 28.0% cases (23/82) by CC method. Among 25 FISH positive cases, typical FISH positive signal pattern (1R1G2F) was displayed in 22 cases and atypical signal pattern (1R2G1F and 2R1G2F) was found in the other 3 cases. Among all 43 AML-M(4)/M(5) cases, the CBFbeta-MYH11 fusion gene was detected in 23.3% cases (10/43) by FISH, which sensitivity was significant higher than that by CC method (2/43) (p < 0.05). It is concluded that some insufficiency of CC technique can be compensated by FISH, and combination of I-FISH with CC technique play a crucial role in diagnosis of CBF AML and in monitoring of minimal residual disease. PMID- 22040963 TI - [Analysis of ITD characteristics in acute myeloid leukemia patients with FLT3-ITD positive]. AB - The aim of this study was to analyze the FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) allelic ratios (AR), number of ITD, ITD length and positions of ITD insertions in de novo acute myeloid leukemia (AML) patients with FLT3-ITD positive, and the relationship between mutant level and therapeutic efficacy. Genomic DNA was amplified by PCR, capillary electrophoresis was used to detect the ITD characteristics in 31 de novo AML patients, and DNA sequences analysis of FLT3-ITD(+) were performed in 13 patients. The results showed that the ratios of mutant to wild type FLT3 allele ranged from 0.01 to 2.8; 28 patients (90.32%) had a single ITD, the remaining 3 patients had more than one ITD; the ITD length ranged from 3 to 144 bp in all FLT3-ITD(+) patients. 13 sequence-analyzed patients, 4 patients were of pure duplications, and 2 patients had foreign bases inserted, and the other 7 patients were partial duplications. The ITD occurred in the regions from p.E573 to p.P606 of the FLT3 protein, with the majority clustered in a stretch between p.F590 and p.R595. The complete remission (CR) rate in AR < 0.5 patients (43.75%) were more prevalent as compared with AR >= 0.5 patients (16.67%) (p > 0.05). It is concluded that the ITD length and AR are vary widely. Some of the insertions are foreign bases, and all of the 13 sequences-analyzed ITD were concentrated on the juxtamembrane domain. The CR rate in patients of AR < 0.5 had no statistical significance compared with patients of AR >= 0.5. PMID- 22040964 TI - [Characteristics of "pre-ALIP" in bone marrow sections of patients with acute myeloid leukemia]. AB - To detect the characteristics of "pre-ALIP" and to investigate their relevance with the development of acute myeloid leukemia (AML) by computer image procession technology, bone marrow (BM) was collected by aspiration/trephine biopsy from AML patients during the complete remission (CR). BM sections were stained by HGF (haematoxylin-Giemsa-acid fuchsin) and photographed by optical microscope imaging system. 4 kinds of computer image segmentation technologies were compared to select the best one for detecting the localization and quantitation of the precursor cells. Planimetry was combined with morphology to segment bone trabeculae. The number of single and double-cluster precursor cells and their distance from bone trabeculae was detected with Euclidean distance change method in BM images of AML patients, and compared with the normal controls. Moreover, the morphological characteristics of "pre-ALIP" were investigated, and the correlation with the development of AML was analyzed. The results showed that the computer image segmentation method based on morphology could identify the precursor cells and bone trabeculae more exactly in BM image, as compared with the methods of 8-Sobel operater. Canny operator and watershed algorithm. Bone trabeculae could be segmented with combinative methods of morphology and planimetry. The number of single precursor cells (19.27 +/- 11.60)/mm(2) and double-cluster precursor cells (1.77 +/- 1.76)/mm(2) in CR group were higher than that in normal controls (p < 0.05). The distance of single precursor cells from bone trabeculae in CR group were closer to bone trabeculae than that in controls [(230.12 +/- 97.68) um vs (260.92 +/- 99.88 um)] (p < 0.05), but the distance of double-cluster precursor cells from bone trabeculae in AML patients was (274.56 +/- 139.48) um, which showed no statistically significant different from controls (p > 0.05), while the double-cluster precursor cells showed the tendency of migrating to the intermediate zone of bone trabeculae compared with the single precursor cells in CR group (p < 0.05). It is concluded that the structure of "pre-ALIP" in BM tissue exists before the occurrence of ALIP. The characteristics of "pre-ALIP" are single and double-cluster precursor cells with abnormal localization or quantitation, which showed correlation with the development of AML. PMID- 22040965 TI - Gene expression of helicase antigen in patients with acute and chronic myeloid leukemia. AB - The aim of this study was to investigate the expression status of the helicase antigen (HAGE) transcript and its clinical significance in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). The expression of HAGE cDNA in bone marrow mononuclear cells from AML and CML patients was detected by using real-time quantitative PCR. The results indicated that overexpression of HAGE transcript (117.12% - 9842.70%, median 434.96%) was detected in 14.8% (11/74) AML patients. AML patients with HAGE cDNA expression were significantly older than those HAGE-negative patients (median 67 and 45 years, respectively, p = 0.001). HAGE cDNA expression was more frequently present among the patients with acute monoblastic leukemia (M(4) and M(5), 7 of 20, 35.0%), compared to the patients with acute non-monoblastic leukemia (M(1), M(2), M(3) and M(6), 4 of 54, 7.4%) (p = 0.007). 28.6% (8/28) cases with normal karyotypes showed HAGE cDNA overexpression, significantly higher than 7.5% (3 of 40) in those with chromosomal abnormalities (p = 0.041). Overexpression of HAGE transcript was found in 9 (34.6%) CML cases and more frequently observed at accelerated phase and blast crisis (4/4, 100%) than that at chronic phase (5/22, 22.7%) (p = 0.008). It is concluded that HAGE cDNA expression is relevant to specific subtypes of AML and to the progression of CML. PMID- 22040966 TI - [Detecting phospho-signaling protein of bone marrow leukemia cells by phospho signaling flow cytometry]. AB - The purpose of this study was to establish the phospho-specific flow cytometry (phospho-flow) to detect the phosphorylated signaling proteins of leukemia cells and to evaluate its useful value in leukemia study. The bone marrow of leukemia children was collected, and treated by phospho-flow of extracted mononuclear cells (MNC) and phospho-flow of directly fixed bone marrow (BM) respectively. In phospho-flow of extracted MNC, the MNC extracted from BM were fixed and permeabilized, then were cultured with P-AKT and P-ERK1/2, finally were analyzed by flow cytometry. In phospho-flow of directly fixed BM, the BM was treated with fixation/lysis buffer and 90% methanol, then were incubated with the surface CD antibody, P-AKT and P-ERK1/2, finally the treated BM cells were analyzed by flow cytometry. The results showed that the positive rates of P-AKT and P-ERK1/2 in MNC treated by phospho-flow of extracted MNC of 26 leukemia children were 46.2% and 30.8% respectively, while the positive rates of P-AKT and P-ERK1/2 in BM treated by phospho-flow of directly fixed BM were 50.0% and 38.5% respectively. The comparison of positive rates of P-AKT and P-ERK1/2 between the 2 treatment protocol showed no difference (p > 0.05). It is concluded that the phospho-flow of directly fixed BM established by our laboratory can be used to analyze the signaling proteins of leukemia cells. PMID- 22040967 TI - [Expression of DNA-dependent protein kinase catalytic subunit in adult acute leukemia and its significance]. AB - This study was aimed to explore the expression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in adult acute leukemia and its correlation with clinical characteristics, karyotype and prognosis. Indirect immunofluorescent cytometry was used to detect the expression of DNA-PKcs in bone marrow mononuclear cells of 105 patients with acute leukemia before chemotherapy and 41 of them after 2 cycles of chemotherapy. Cytogenetic data were obtained from 26 of them by R band karyotypic analysis. The results showed that the expression of DNA PKcs was correlated with higher WBC count level in peripheral blood (p < 0.05), but was not obviously associated with median age, gender, percentage of bone marrow blasts, clinical classification, median hemoglobin level and median platelet count (p > 0.05). The middle and strong positive expression of DNA-Pkcs in non-remission group was significantly higher than that in remission group (p < 0.05). The positive rate of DNA-PKcs in abnormal chromosome group was significantly higher than that in chromosome normal group (p < 0.05). It is concluded that the DNA-PKcs expression level is closely related with the increased WBC count, and the expression of DNA-PKcs is correlated also with karyotype and clinical prognosis in adult acute leukemia. PMID- 22040968 TI - [Plasma levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in patients with newly diagnosed lymphomas]. AB - The objective of this study was to detect the expression levels of VEGF-C, VEGF D, VEGFR-2 and VEGFR-3 in plasma of newly diagnosed lymphoma patients, and analyze their possible relationships with clinicopathological characteristics and prognosis. The expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma from 86 newly diagnosed lymphoma patients were detected by enzyme-linked immunosorbent assay (ELISA). As a results, the multivariate analysis showed that VEGF-C level in non-Hodgkin's lymphoma patients was low, but high in Hodgkin's lymphoma patients; VEGFR-2 level was higher in patients > 60 years, while VEGF-D level was lower in patients with IPI > 2. The univariate analysis showed that VEGF-D level was lower in patients with IPI > 2, while VEGF-D and VEGF-C levels were higher in patients without B symptoms. Relationship analysis between these factors indicated that the relation of VEGF-D expression level with VEGFR-2 and VEGFR-3 was positive. It is concluded that VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 play important roles in the pathogenesis of lymphoma, and may be used as indicators of prognosis evaluation or even guide for the antiangiogenesis treatment of lymphoma. PMID- 22040969 TI - [Sequentially inducting murine embryonic stem cells into hematopoietic stem cells in vitro by hematopoietic development procedure for reconstitution of hematopoiesis in vivo]. AB - This study was purposed to directly induce murine embryonic stem cells (ESC) into hematopoietic stem cells (HSC) by simulating the spatial and temporal hematopoietic microenvironment changes in embryonic development, and to investigate the function of in vivo hematopoietic reconstitution of these HSC. E14 ESC were induced into embryoid body (EB) firstly. Then the cells from EB were further co-cultured with human aorta-gonad-mesonephros (AGM) region, fetal liver (FL) and bone marrow (BM) stromal cells in Transwell non-contact system in sequential orders. After 6 days of each co-cultured stage, the induced cells derived from EB were collected to analyze the Sca-1(+)c-Kit(+) cells by flow cytometry, check teratoma formation and transplant to BALB/C female mice exposed to lethal dose (60)Co gamma-ray. The recipient mice were divided randomly into 5 groups: AGM, AGM + FL, AGM + FL + BM, irradiation control and normal control groups. The survival rates, hematopoietic reconstitution and engraftment of donor cells in the different groups were monitored. The results showed that Sca-1(+)c Kit(+) cell level in EB cells co-cultured with human AGM region and FL stromal cells reached to peak value (21.96 +/- 2.54)%. Teratomas could be found in NOD SCID mice after subcutaneous injection of EB cells co-cultured with human AGM region stromal cells, while there was no teratoma in the mice after subcutaneous injection of EB cells induced by human AGM region and FL stromal cells. The recipients in AGM group and irradiation control group all died. The survival rate was 77.8% in AGM+FL group, and 66.7% in AGM+FL+BM group. The peripheral blood cell count was near normal at day 21 after transplantation, and Sry gene copies from donor could be detected in recipient mice of these two groups. It is concluded that sequentially inductive system with feeder cells from human AGM region, fetal liver and bone marrow simulating embryonic defined hematopoiesis procedures can enhance the directed differentiation of ESC into HSC which can safely reconstitute hematopoiesis in vivo. PMID- 22040970 TI - [Analyzing hematopoietic development of mouse embryonic AGM region by tissue culture]. AB - To analyze hematopoietic kinetics of mouse embryonic aorta-gonad-mesonephros (AGM) region, an in vitro tissue culture method was developed in this study, partly based on previous reports. After 2 days of tissue culture, a significant number of erythro myeloid progenitors, as quantitated by colony forming assay was detected in the AGM region. Moreover, the cells from cultured E10.5 AGM region could generate 10.8 +/- 3.5 colony-forming unit in spleen (CFU-S) per tissue on average. Transplantation of cultured E10.5-E11.0 AGM cells resulted in efficient (85.7% repopulated) and long-term (> 4 months) reconstitution of lethally irradiated adult recipients with remarkable chimerism [(51.12 +/- 21.17)%]. The multilineage contribution of donor cells was validated by significant engraftment of myeloid and/or lymphoid cells in peripheral blood, bone marrow, spleen and thymus of recipients. Taken together, the tissue culture method can enable us to manipulate the AGM region in vitro, fulfilling a systematic evaluation of developmental kinetics of various hematopoietic precursor cells, particularly HSC, in normal and mutant mid-gestation mouse embryos. PMID- 22040971 TI - [RUNX1 regulates transcription activity of WNT5A in mouse bone marrow derived mesenchymal stem cells]. AB - This study was purposed to investigate the effect of RUNX1 on transcription activity of WNT5A promoter in mouse bone marrow derived mesenchymal stem cells (MSC), and to explore the mechanism by which bone marrow environments regulate MSC. RT-PCR was used to detect the expression of RUNX1 in MSC isolated from mouse bone marrow and cultured in vitro; the chromatin immunoprecipitation (ChIP) was used to investigate the direct in vivo interaction between the RUNX1 and WNT5A promoter; retrovirus system was utilized to introduce the RUNX1 gene into MSC to detect the regulation of RUNX1 on the transcription activity of WNT5A promoter. The results showed that mouse bone marrow derived MSC was positive for Oil Red O, van Kossa and toluidine blue staining respectively and RUNX1 expressed in MSC. WNT5A promoter could be bound by RUNX1, and the expression level of WNT5A was enhanced with the increase of RUNX1. It is concluded that RUNX1 expresses in mouse bone marrow derived MSC, WNT5A is a direct target gene of RUNX1 and its transcriptional activity is regulated by RUNX1. PMID- 22040972 TI - [Effect of proteasome inhibitor on migration ability and hepatocyte growth factor expression of bone marrow mesenchymal stem cells in multiple myeloma patients]. AB - This study was aimed to investigate the effect of proteasome inhibitor bortezomib on the migration ability and hepatocyte growth factor (HGF) expression of bone marrow mesenchymal stem cells (MSC) in multiple myeloma patients. Transwell assay was employed to measure the migration ability of bone marrow MSC in vitro before and after treatment with bortezomib. The HGF mRNA expression level was determined by real-time quantitative PCR. The results indicated that after treated with bortezomib of concentrations of 2.5 nmol/L for 48 hours, the migration activity of MSC decreased significantly as compared with control cohorts (p < 0.05). The HGF mRNA level in MSC after bortezomib treatment was significantly lower than that of control group (p < 0.05). It is concluded that bortezomib can inhibit the migration and down-regulate HGF mRNA expression of bone marrow MSC in multiple myeloma patients. PMID- 22040973 TI - [Effects of mesenchymal stem cells on lymphocyte proliferation of sensitized mice in vitro and their action manner]. AB - This study was purposed to investigate the effects of mesenchymal stem cells (MSC) on lymphocyte proliferation of sensitized mice in vitro and their action manner so as to more understand the possible mechanisms of bone marrow-derived MSC action on the engraftment of hematopoietic stem/progenitor cells in sensitized mice. Bone marrow-derived MSC were cultured by adherent culture method, the MSC or culture supernatant were used as immune cells or immunologic factor, the spleen lymphocytes of sensitized mice were used as effector cells. The phytohemagglutinin (PHA) was used to stimulate the lymphocyte proliferation, the MTT method was used to detect the mixed lymphocyte reaction. The results showed that bone marrow-derived MSC could inhibit the lymphocyte proliferation of sensitized mice, the MSC cultured supernatant also exhibit this effect. Moreover, the inhibitory effect of MSC supernatent increased along with the increase of cell ratio and concentration, while ratio of these two kind of cells was 1:1, the inhibitory effect was the highest (p < 0.05). It is concluded that the MSC can suppress lymphocyte proliferation of sensitized mice in vitro through cell-cell direct contact or cell-cell indirect interaction. PMID- 22040974 TI - [Biological effects of low dose X-irradiation on human bone marrow mesenchymal stem cells]. AB - Recent studies have shown that low dose X-irradiation shows specific effect different from high dose exposures. However, the biologic responses of bone marrow mesenchymal stem cells (BM-MSC) to low dose X-irradiation have rarely been described in the literature. This study was purposed to investigate the biologic responses of human bone marrow-derived MSC to low dose X-irradiation. The proliferation of cells was tested with MTT assay, so that the cell growth curve was drawn at 1 to 7 days. The expression of survivin mRNA was detected by RT-PCR assay; the BM-MSC DNA damage induced by X-irradiation were detected with mononuclear cell gel electrophoresis. The results indicated that the proliferative ability of BM-MSC exposed to low doses of X rays was obviously enhanced as compared with control group. The low dose X-irradiation caused the damage of DNA in X-ray dose dependent manner. X-irradiation enhanced expression of survivin in MSC. It is concluded that the low dose below 20 cGy of X irradiation has a promoting effect on survivin expression in BM-MSC. Whether the high expression of survivin plays an important role to resist ionizing radiation needs to be further studied. PMID- 22040975 TI - [Infection of the mononuclear cell subpopulations in murine bone marrow with murine cytomegalovirus]. AB - This study was aimed to explore the infection characteristics of murine mononuclear cell subpopulations in bone marrow with murine cytomegalovirus (MCMV). Subpopulations of mononuclear cells, including lin(+), lin(-), lin( )CD117(+) and lin(-)CD117(-) cells, were infected with MCMV after being separated by MACS, and induced to differentiation by adding cytokines or inducer, then nucleic acid and proteins were detected. The results indicated that the MCMV DNA, IE transcripts and IE protein could be detected in the lin(+) cells infected with MCMV; no virus products were detected in infected lin(-) cells without adding any stimulating factors, while IE and E transcripts and proteins were detected after adding GM-CSF, rhEPO or phorbol ester in the lin(-) cells infected with MCMV. Furthermore, no IE or E gene transcripts were detected in the lin(-)CD117(+) and lin(-)CD117(-) cells, but the cell colony formation of lin(-)CD117(+) hematopoietic stem and progenitor cells was inhibited after MCMV infection and expression of CD117 antigen on cell surface of the lin(-) cells was downregulated. It is concluded that MCMV can latently infect subpopulations of mononuclear cells in the murine bone marrow. Cells which are of characteristics of primitive stem and progenitor cells are not susceptible to MCMV, but infection of these cells with MCMV can inhibit functions of cells and downregulate the expression of antigen on cells surface. PMID- 22040976 TI - [Comparison of immunologic regulatory characteristics of mesenchymal stem cells derived from human umbilical cord amnion and adult bone marrow]. AB - This study was aimed to compare the immunoregulatory effects of mesenchymal stem cells derived from human umbilical cord amnion (AMSC) and adult bone marrow (BMMSC) in vitro, so as to provide the experimental basis for allogeneic hematopoietic stem cell transplantation in clinic. The AMSC were isolated from human umbilical cord amnion by using digestion with collagenase. They were identified by morphology, growth characteristics, immunophenotyping and differentiation ability. Furthermore, the immunoregulatory effects of AMSC and BMMSC were tested by lymphocyte transformation and mixed lymphocyte reaction. The results showed that AMSC and BMMSC possessed similar biological characteristics such as exhibition of fibroblastic morphology and strong proliferation ability in vitro. Flow cytometric analysis revealed that the AMSC highly expressed CD73, CD90, CD105, but negative for CD34, CD45, HLA-DR, and CD86 of BMMSC. Functionally, they all could differentiate into adipocyte, osteocytes and chondrocytes. Moreover, AMSC could inhibit cellular or nonspecific mitogenic stimuli-induced T cell proliferation with a dose-dependent manner. Reverse transcriptional-polymerase chain reaction also demonstrated expression of the similar immune cytokines in AMSC and BMNSC. It is concluded that the MSC derived from human umbilical cord amnion may be an excellent alternative source for experimental and clinical application. PMID- 22040977 TI - [Effect of endothelium-specific deletion of PTEN on hemangioblast development in mouse embryo AGM region]. AB - This study was aimed to investigate whether endothelium-specific deletion of PTEN can affect hemangioblast development in the AGM region of mouse embryos. Based on Cre/loxP system, the Tie2CrePten(loxp/loxp) and Tie2CrePten(loxp/wt) mouse embryos were obtained. The genotype was identified by PCR. After treated with type I collagenase, the AGM region was dispersed into single-cell suspension, and then was cultured in blast colony-forming cell (BL-CFC) media. The number of BL CFC was counted 4 or 5 days later. The hematopoietic capacity of BL-CFC was detected in methylcellulose culture system and the endothelial potential was assessed by tube-like structure formation on Matrigel. The results showed that the number of BL-CFC in AGM region of Tie2CrePten(loxp/loxp) mouse embryo decreased as compared with Tie2CrePten(loxp/wt) embryo. Whereas the hematopoietic capacity of mutant BL-CFC was enhanced, the endothelial potential, as evaluated by tube-like structure formation in vitro, was significantly reduced. It is concluded that the endothelial PTEN is capable of exerting regulatory functions on both the numbers and the dual potential of hemangioblast in mouse AGM region. PMID- 22040978 TI - [Bortezomib combined with autologous peripheral blood hematopoietic stem cell transplantation for therapy of patients with multiple myeloma]. AB - This study was aimed to evaluate the therapeutic efficacy of bortezomib combined with autologous peripheral blood hematopoietic stem cell transplantation (autoPBSCT) for patients with multiple myeloma (MM). 5 patients underwent autologous hematopoietic stem cell transplantation. Bortezomib treatment was supplied for patients before autoPBSCT and in the conditioning of transplantation, it was also used in maintaining treatment. Patients with transplantation adopted bortezomib plus melphalan conditioning regimen. The number of infused MNC and number of CD34(+) cells were 4.06*10(8) (4.09*10(8) - 4.37*10(8))/kg and 3.98*10(6) (2.49*10(6) - 8.2*10(6))/kg respectively. The results showed that hematopoiesis was reconstituted in 5 patients, with a neutrophil cell count more than 0.5*10(9)/L at day 14 (13 - 25 days) after transplantation and platelet count more than 50*10(9)/L at day 28 (21 - 41 days) after transplantation. Transplantation-associated death was not observed. 5 patients were disease-free survival. In conclusion, treatment of bortezomib combined with autologous peripheral hematopoietic stem cell transplantation is an effective method for patients with multiple myeloma. Use of bortezomib after transplantation might still be favourable to MM patients, for survival prolongation and life quality improvement. PMID- 22040979 TI - [Peripheral blood stem cell collection from ABO incompatible allogeneic donors and its effect in hematopoietic stem cell transplantation]. AB - The study was aimed to evaluate the yield of the COBE Spectra blood cell separator with auto-peripheral blood stem cell program for collection of peripheral blood hematopoietic stem cells (PBHSC) from HLA-matched ABO incompatible allogeneic PBHSC donor, and observe the safety and effect of allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBHSCT) without removal of erythrocytes and plasma. PBHSC from 28 allogeneic donors were collected by COBE Spectra blood cell separator with auto-peripheral blood hematopoiEtic stem cell (auto-PBHSCT) program. Control group included 15 HLA matched patients who received allo-PBHSCT with ABO-compatible grafts. The amount of PBHSC was harvested and the parameter was modified according to the hematocrit and mononuclear cell (MNC) counts of donors. The nucleated cell count, proportion of MNC, number of CD34(+) cells were detected, and reconstitution status of hematopoietic function and time for change into donor's blood group were observed. The results showed that the nucleated cell count proportion of MNC and number of CD34(+) cells showed no significant difference between groups of ABO incompatible and compatible (p > 0.05). All their hematopoietic functions were reconstituted. Between the ABO incompatibility and the compatible groups, the time of neutrophil and platelet recovery was not significantly different (p > 0.05), In ABO blood major incompatible and the compatible groups, the recovery of erythropoiesis were significantly delayed (p < 0.01). The blood type of 18 patients in ABO incompatible group was turned into donor's blood type successfully at 35-139 days after transplantation. It is concluded that major ABO incompatibility did not affect the erythropoiesis reconstitution in HLA matched allo-HSCT. the major incompatibility may be a main reason of erythropoietic delay. PMID- 22040980 TI - [Efficacy of haploidentical allogeneic bone marrow hematopoietic stem cell transplantation combined with umbilical cord blood derived mesenchymal stem cells for severe aplastic anemia]. AB - The aim of this study was to investigate the effect of haploidentical allogeneic bone marrow or peripheral blood hematopoietic stem cell transplantation (allo HSCT) combined with umbilical cord blood mesenchymal stem cell (MSC) infusion in treatment of severe aplastic anemia (SAA). Five SAA patients received haploidentical allo-HSCT combined MSC infusion. HSC and MSC were collected from bone marrow or peripheral blood of haploidentical donors and umbilical cord blood respectively. After transplantation, the clinical hematopoietic reconstitution and early complications were monitored. The results indicated that all the 5 patients achieved hematopoietic reconstitution. The average time for WBC count > 2*10(9)/L was 13.8 days, and average time for Plt level > 20*10(9)/L was 17.8 days. The STR-PCR detection of patient peripheral blood at day 30 after transplantation showed that engraftment was complete donor's gene type. The communication with 1 patient was broken off because of his epilepsy, other 4 patients are all alive in diseases-free state. In conclusion, the haploidentical allo-HSCT combined with umbilical cord MSC infusion is an effective approach to cure SAA, which needs to be further studied in a large number of cases. PMID- 22040981 TI - [Polymorphism in BP1 binding site upstream of beta-globin gene in Chinese Han population]. AB - This study was aimed to analyze the BP1 binding site sequence upstream of beta globin gene in Chinese Han population, and to investigate polymorphism in the BP1 binding site upstream of beta-globin gene, so as to provide the basis for exploration of relation between polymorphisms in the BP1 binding site and beta globin expression. Genomic DNA was extracted from peripheral leukocytes of 110 healthy individuals in Chinese Han population. Sequence of the BP1 binding site upstream of beta-globin gene was amplified by polymerase chain reaction, the polymorphic variation in the BP1 binding site was determined by DNA sequencing. The results indicated that 2 polymorphism loci were found in the BP1 binding site upstream of beta-globin gene, they were C/T at the -551 bp region and (AC)(n)(AT)(x)T(y) at the -530 bp region in Chinese Han population. Frequencies of C and T were 60.4% and 39.6% at position -551. Analysis of the (AC)(n)(AT)(x)T(y) polymorphism revealed 9 different genotypes: (AC)(2)(AT)(9)T(5), (AC)(2)(AT)(8)T(5), (AC)(2)(AT)(7)T(7), (AC)(3)(AT)(7)T(5), (AC)(2)(AT)(8)T(9), (AC)(3)(AT)(8)T(5), (AC)(2)(AT)(10)T(3), (AC)(2)(AT)(11)T(3), and (AC)(2)(AT)(7)T(5) at position -530. Frequencies of 9 (AC)(n)(AT)(x)T(y) polymorphisms were 33.2%, 29.1%, 24.1%, 5.4%, 3.2%, 1.8%, 1.4%, 0.9%, and 0.9% respectively. It is concluded that rich (AC)(n)(AT)(x)T(y) polymorphisms at the 530 bp region in the BP1 binding site upstream of beta-globin gene are found in Chinese Han population. (AC)(2)(AT)(9)T(5), (AC)(2)(AT)(8)T(5), and (AC)(2)(AT)(7)T(7) are 3 major polymorphisms among Chinese Han population, and (AC)(3)(AT)(8)T(5) is a novel polymorphism at the -530 bp region. More studies should be done to explore relation between (AC)(n)(AT)(x)T(y) polymorphisms and beta-globin expression. PMID- 22040982 TI - [Construction and expression of recombinant plasmid to initiate polarization and activation of regulatory T cells]. AB - In order to construct a recombinant plasmid initiating the polarization and activation of the regulatory T cells (Treg), the fragments of hTGF-beta1 and C2 C4 of gp120 amplified by RT-PCR and cloned into pCR2.1 vector respectively. hTGF beta1 and C2-C4 DNA fragments were obtained, then sub-cloned to generate the prokaryotic expression vector named pET-28a/C2-C4-Linker- hTGF-beta1. The expression of recombinant protein was induced by IPTG (0.1 mmol/L) for 6 hours. The results showed that the fragments of hTGF-beta1 and C2-C4 were amplified and cloned into pCR2.1, the prokaryotic expression vector pET-28a/C2-C4-Linker- hTGF beta1 was constructed successfully. The recombinant protein was expressed as inclusion body after being induced by IPTG. It is concluded that this recombinant protein can initiate the polarization and activation of Treg cells, indicating the engineering E.coli strain is successfully obtained. PMID- 22040983 TI - Infection and eradication of Helicobacter Pylorus affecting etiology and curative effect of idiopathic thrombocytopenic purpura: a META analysis. AB - The study was aimed to explore the relationship between infection of Helicobacter Pylorus (H. Pylorus) and etiology of idiopathic thrombocytopenic purpura (ITP) and evaluate whether H. Pylorus eradication can increase platelet count in patients with ITP. The data-bases of cqvip, Wanfang, TsingHua TongFang, CNKI and PubMed were searched, inclusion and exclusion criteria and heterogeneity test were determined. The studies of H. Pylorus infection and ITP were investigated with fixed effect mode Meta-analysis. Relationship between H. Pylorus infection and etiology of ITP, H. Pylorus eradication and curative effect of ITP were comprehensively and quantitatively evaluated. OR > 1 indicated that factor of exposure was the risk factor of disease; OR < 1 suggested that factor of exposure was the protective factor of disease; OR = 1 revealed that there were no correlation between factor of exposure and diseases. 95%CI was the confidence interval of total OR. The results showed that a total of 211 cases and 210 controls from 5 studies was included to evaluate the exposure of H. Pylorus between ITP patients and controls, the pooled OR was 1.73 (95%CI = 1.12 - 2.67); a total of 458 cases and 305 controls from 13 studies was included to evaluate the relationship between H. Pylorus eradication and curative effect of ITP, the pooled OR was 6.53 (95%CI = 4.44 - 9.61). It is concluded that H. Pylorus infection plays a role in the etiology of ITP. Eradication of H. Pylorus increases platelet count in patients with ITP. H. Pylorus eradication can be used as the first line measure to treat H. Pylorus-positive ITP. PMID- 22040984 TI - [Cyclooxygenase inhibitors in some dietary vegetables inhibit platelet aggregation function induced by arachidonic acid]. AB - The study was purposed to investigate whether the cyclooxygenase inhibitors from some dietary vegetables can inhibit platelet aggregation function by the arachidonic acid (AA). The vegetable juice was mixed with platelet rich plasma (PRP), and asprin was used as positive control. The maximum ratio of platelet aggregation induced by AA was measured on the aggregometer; heme and cyclooxygenase-1 (COX(1)) or cyclooxygenase-2 (COX(2)) were added to test tubes containing COX reaction buffer, the mixture was vortex-mixed and exposed to aspirin or vegetable juice, followed by addition of AA and then hydrochloric acid (1 mol/L) was added to stop the COX reaction, followed by chemical reduction with stannous chloride solution. The concentration of COX inhibitors was detected by the enzyme immunoassay kit; vegetable juice (aspirin as positive control) was mixed with whole blood, which was followed by the addition of AA, and then the reaction was stopped by adding indomethacin, centrifuged, then the supernatant was collected, and the plasma thromboxane B(2) (TXB(2)) was measured by radioimmunoassay. The results showed that spinach juice, garlic bolt juice, blanched garlic leave juice and Chinese leek juice could inhibit by 80% human platelet aggregation induced by AA. 4 kinds of vegetables were all found a certain amount of cyclooxygenase inhibitors, which COX(1) and COX(2) inhibitor concentrations of spinach were higher than that of aspirin; 4 vegetable juice could significantly reduce the human plasma concentrations of TXB(2) induced by AA (p < 0.05). It is concluded that 4 kinds of raw vegetables containing cyclooxygenase inhibitors inhibit the production of TXA(2) and thus hinder platelet aggregation. Raw spinach, garlic bolt, blanched garlic and chinese leek inhibit significantly AA-induced human platelet aggregation in vitro. 4 kinds of vegetables may have a good potential perspective of anti-platelet aggregation therapy or prevention of thrombosis. PMID- 22040985 TI - [Expression and clinical significance of CD4(+)CD25(+)Treg cells, sFas and sFasL in peripheral blood of patients with autoimmune thrombocytopenic purpura]. AB - This study was aimed to detect the expression of CD4(+)CD25(+) regulatory T cells (Treg), sFas and sFasL in patients with autoimmune thrombocytopenic purpura (AITP), and to explore their roles in the pathogenesis of AITP and clinical significance, so as to provide a theoretical basis for effective treatment for AITP. The expressions of CD4(+)T, Treg, CD4(+)CD25(-)T, Treg/CD4(+)T in peripheral blood of 30 the patients with AITP and 18 controls were detected by flow cytometry, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of sFas and sFasL in peripheral blood of controls and the patients with AITP before and after treatment. The results indicated that the expression rate of CD4(+)T in AITP patients was lower than that in the control (p < 0.05), and the expression rates of Treg and Treg/CD4(+)T were significantly lower than those of control (p < 0.01), but the expression rate of Treg between the two group had no difference (p > 0.05). The levels of sFas and sFasL in the peripheral blood of the patients before treatment were significantly higher than that after treatment and control group (p < 0.01), and no difference between the patients after treatment and the control group (p > 0.05) was found. The expression rates of Treg, Treg/CD4(+)T were positively related with the platelet count and the level of sFas was positively related with the level of sFasL in the peripheral blood of AITP before treatment. There were no significant correlation between the levels of CD4(+)T, Treg, sFas, sFasL and the platelet count. No correlation was seen between the expression of Treg and sFas, sFasL. It is concluded that CD4(+)CD25(+) Treg play a role in the pathogenesis of AITP; the expression rate of Treg is associated with the severity of AITP; the abnormal levels of sFas and sFasL participate in the immune pathogenesis of AITP. PMID- 22040986 TI - [Proportion of CD34(+)CD38(-) cell population in bone marrow of patients with de novo AML as prognostic factor of complete remission at first course of induction chemotherapy]. AB - This study was to investigate the relationship between the CD34(+)CD38(-) cell population and its proportion in G(0) phase of de novo AML non-M(3) at diagnosis and the clinical and experimental characteristics. The flow cytometry was used to detect the expression of the cell surface antigen CD34 and CD38 in the bone marrow mononuclear cells (MNC) of the AML non-M(3) at diagnosis and investigate the cell cycle of the subpopulations, and then the relationships between the proportion of CD34(+)CD38(-)cell population and its G(0) state and the complete remission (CR) rate after the first induction chemotherapy was analyzed. The results showed that the proportion of the CD34(+)CD38(-) cell population and its G(0) phase had no relationship with the karyotypes and WBC count at new diagnosis and the Flt3/ITD status, but correlate with the blasts in the bone marrow after the first course induction chemotherapy. The proportion of the CD34(+)CD38(-) cells in patients who have visible blasts in the bone marrow at day 7 after completion of the first course induction chemotherapy was (12.47 +/- 26.26)%, but the counterparts was (2.62 +/- 7.20)% in the group of patients whose bone marrow had no visible blasts (p = 0.031). The proportion of the CD34(+) cell population in patients who had visible blasts in the bone marrow at day 1 after completion of the first course induction chemotherapy was (17.40 +/- 21.20)%, yet the proportion of the CD34(+) cell populations was (5.64 +/- 6.96)% in the patients who had no visible blasts in the bone marrow (p = 0.001). The proportion of the CD34(+)CD38(-) cell populations in the patients who achieved CR after the first course induction chemotherapy was (2.51 +/- 9.72)%, which was lower than the proportion (24.92 +/- 27.04%) of the non-CR patients (p = 0.001). Furthermore, the proportion (1.60 +/- 4.82%) of the CD34(+)CD38(-) cell population in the AML non-M(2b) CR patients was more obviously lower than that in the non-CR patients (p < 0.001). In univariate analysis, whether or not achieved CR after the first course induction chemotherapy correlated with age (p = 0.022), the proportion of the CD34(+)CD38(-) cell population (p = 0.008) and the proportion of the visible blasts in the bone marrow at day 7 after induction therapy (p = 0.011). Multivariate analysis showed that only the proportion of the CD34(+)CD38(-) cells had correlation tendency with CR rate. It is concluded that the proportion of the CD34(+)CD38(-) cells in bone marrow of de novo AML non-M(3) is a prognostic factor to anticipate the CR rate of the first course for induction therapy. PMID- 22040987 TI - [Clinical significance of serum NGF level and CD271 expression in patients with acute B lymphoid leukemia]. AB - The aim of this study was to detect the nerve growth factor (NGF) level in serum and NGF low affinity acceptor CD271 expression on bone marrow leukemic cells in acute B lymphoid leukemia (B-ALL) patients and to analyze their clinical significance. The NGF level in serum and CD271 expression on leukemic cells in bone marrow were detected by enzyme linked immunosorbent assay and flow cytometry in B-ALL patients respectively. The results indicated that compared with control group, the NGF level in serum of patient group significantly increased (t = 4.191, p < 0.05), but CD271 expression on leukemic cells in bone marrow decreased significantly (t = 4.898, p < 0.05). The complete remission (CR) rate of 25 B-ALL patients was 64% (16/25) after one course of CVAD chemotherapy. There were statistically significant differences of NGF level and CD271 expression in non remission (NR) group and control group (t = 3.976, p < 0.05 vs t = 5.052, p < 0.05), but there were no statistically difference of NGF level and CD271 expression in CR group (t = 1.102, p > 0.05 vs t = 1.150, p > 0.05) as compared with control group. The CD271 expression before and after chemotherapy between CR and NR groups showed statistically significant differences (t = 3.889, p < 0.05; t = 3.751, p < 0.05 and t = 4.678, p < 0.05 respectively), but NGF level before and after chemotherapy showed no statistical difference between these 2 groups (t = 0.476, p > 0.05). 50% (8/16) patients relapsed during following up, and of their NGF level [(168.00 +/- 61.66) pg/ml] and CD271 expression [(52.29 +/- 13.00)%] showed the significantly differences, compared with those in control group (t = 5.284, p < 0.05 vs. t = 6.073, p < 0.05), but the NGF level [(81.13 +/ 25.32) pg/ml] and CD271 expression [(78.45 +/- 7.12)%] of other 8 patients showed no statistical difference as compared with control group (t = 1.228, p > 0.05 vs t = 1.144, p > 0.05). Compared with low NGF level and CD271 low expression groups, the survival time of B-ALL patients with high NGF level and CD271 expression was not changed significantly (p = 0.750 vs p = 0.170). It is concluded that the increased NGF level in serum and decreased CD271 expression on bone marrow leukemic cells in B-ALL patients are related with leukemia development and may be the useful indexes to evaluate curative effect and prognosis. PMID- 22040988 TI - [Clinical study on combination of homoharringtonine, Ara-C and idarubicin induction for treatment of newly diagnosed acute myeloid leukemia patients]. AB - The purpose of this study was to assess the efficacy and toxicity of HAI regimen [(homoharringtonine 2.5 mg/(m(2)*d), days 1 - 7; cytarabine 150 mg/(m(2)*d), days 1 - 7; idarubicin 9 mg/(m(2)*d), days 1 - 7)] for induction treatment of newly diagnosed acute myeloid leukemia (AML) (except acute promyelocytic leukemia). 31 patients with newly diagnosed AML, aged 39 (14 - 58) years, were enrolled in this clinical study. The complete remission (CR) rate, especially after one course, the overall survival (OS) rate and relapse free survival (RFS) rate were estimated. The outcomes were compared between different prognostic groups according to World Health Organization (WHO) classification, genetics and initial WBC count. Safety was evaluated using standard WHO criteria. The results showed that 26 patients (84%) achieved CR after 1 course of induction. The CR rate for the patients with favorable, intermediate and unfavorable cytogenetics was 90%, 88% and 60% respectively. All 7 patients with a high initial WBC count (>= 100*10(9)/L) obtained CR, while 19 out of 24 without a high initial WBC count obtained CR. With a median follow-up of 15(range 2-56) months, the estimated 3 year OS rate for all patients and the patients with CR was 44% and 52% respectively. The 3-year RFS rate was 51%. The patients receiving induction chemotherapy died of the chemotherapy. Profound myelosuppression was seen in all patients after the HAI induction with the median duration of neutropenia (ANC < 0.2*10(9)/L) of 16 (6 - 24) days. As the most common toxicity, severe infections (grade III-IV) involved in all the patients and the duration of febris was 6 (1 - 36) days. The incidence of septemia and invasive fungus infection were 19.4% and 45.2% respectively. The incidence of non-infection fever, increased glutamic pyruvic transaminase (GPT), diarrhea, increased bilirubin and oral cavity mucositis were 6.5%, 6.5%, 3.2%, 3.2%, 3.2% respectively, as the more frequent severe non-hematological toxicities. It is concluded that HAI regimen is a high efficient induction schedule for the newly diagnosed AML, and archive the higher CR rate after one course than DNR/Ara-C standard induction regimen. Side effects are acceptable, except severe infection. PMID- 22040989 TI - [Detection of BCR/ABL fusion gene by fluorescence in situ hybridization and its clinical application]. AB - This study was aimed to investigate the clinical value of detecting BCR/ABL fusion gene by fluorescence in situ hybridization (FISH). The conventional cytogenetic test and detection of BCR/ABL fusion gene by FISH for bone marrow of patients with newly diagnosed chronic myeloproliferative disease or myelodysplastic and myeloproliferative disorders, acute lymphocytic leukemia and chronic myelogenous leukemia (CML) after allogeneic hematopoietic stem cell transplantation were carried out. The results showed that (1) out of 46 newly diagnosed as chronic myeloproliferative disease or myelodysplastic and myeloproliferative disorders, 22 cases were diagnosed as CML, the FISH detection showed all positive (100%), while cytogenetic test showed 86.4% (19/22) positive, in the other 24 patients who were diagnosed as other chronic myeloproliferative disease or myelodysplastic and myeloproliferative disorders, BCR/ABL fusion gene all were be detected as negative 100% by FISH, while the cytogenetic test of bone marrow in 3 cases supported the diagnosis of CML, and the diagnosis of myelodysplastic disorder in 1 case; (2) in 3 out of 7 acute lymphocytic leukemia cases the BCR/ABL fusion gene could not be detected by FISH; (3) the BCR/ABL fusion gene could be detected by FISH in 2 cases of CML received allogeneic hematopoietic stem cell transplantation, with abnormal threshold 6.5% and 1.2% respectively. It is concluded that the detection of BCR/ABL fusion gene by FISH is sensitive and reliable, which is very important for the diagnosis and differential diagnosis of chronic myeloproliferative disorders, myelodysplastic and myeloproliferative disease, as well as definite diagnosis of Ph(+) acute lymphoblastic leukemia. This method also has an important significance for monitor of minimal residual disease in CML patients received allogeneic hematopoietic stem cell transplantation. PMID- 22040990 TI - [Clinical characteristics and efficacy of anti-Aspergillus therapy in patients with hematological malignancies and invasive aspergillosis]. AB - This study was aimed to analyze the clinical features, anti-fungal therapeutic efficacy and safety in hematological malignancy patients with invasive aspergillosis (IA) after hematopoietic stem cell transplantation (HSCT) or chemotherapy. The patients with hematological malignancies received chemotherapy or HSCT were analyzed retrospectively, then the clinical characteristics and diagnosis were analyzed according to the diagnostic criteria for IA. The efficacy and safety of anti- Aspergillus therapy, and the factors influencing therapeutic response were evaluated. The results showed that out of 30 cases with IA, 2 were proven, 19 were probable, 9 were possible, and 19 were diagnosed after HSCT, most in the late period after-HSCT (> 40 d). 8 cases received fluconazol only, 6 received caspofungin only, 7 received combined therapy. The efficacy and time interval from the first day of treatment to successful response (TTR) were 87.5%, 50% and 85.7% and 38, 20 and 36 days, respectively. Combined therapy is better than single drug treatment (p < 0.05) while the TTR was not significantly different between them. The factors influencing the therapeutic efficacy were as follows: age, HSCT, GVHD and CMV, previous IFI and so on (p < 0.05). All the anti Aspergillus medicines resulted in some injury of hepatic and renal function. However, there were no significant difference between the drugs or between combination and single drug therapy (p > 0.05). It is concluded that IA is also the major and severe complication in the patients with hematological malignancies or received HSCT. Combined therapy for anti- aspergillus is better than single drug in efficacy and safety, without increasing the adverse drug reactions for hepatic and renal function. The efficacy of anti- aspergillus may be related to age, HSCT, GVHD and CMV, previous IFI and so on. PMID- 22040991 TI - [Effect of G-CSF on murine thymocyte emigration and cell cycle alteration after a sublethal dose of irradiation]. AB - This study was aimed to investigate the effect of recombinant human granulocyte colony-stimulating factor(G-CSF) on murine thymocyte emigration and cell cycle alteration after a sublethal dose of gamma-irradiation. Female BALB/c mice were given 6.0 Gy gamma-ray total body irradiation and then randomly divided into G CSF and control groups. Mice in the G-CSF group were injected recombinant human G CSF 100 ug/(kg.d) subcutaneously once daily for 14 consecutive days and mice in the control group were given the same volume of phosphate buffered solution. Thymocyte cycle alteration and the proportion of apoptosis cells were detected by flow cytometry within 72 hours after irradiation. Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTREC) of the thymic cells at 30 and 60 day after the irradiation. The results showed that at 6 hour after irradiation G-CSF could significantly increase the thymic cells in G(0)/G(1) phase, G-CSF vs control: (82.0 +/- 5.0)% vs (75.9 +/- 2.8)% (p < 0.05), and decrease the thymic cells in S phase, G-CSF vs control: (10.2 +/- 4.8)% vs (15.7 +/- 2.3)% (p < 0.05), but G-CSF seemed have no evident effects on the percentage of thymic cells in G(2)/M phase. G-CSF could also protect thymocytes from apoptosis at 6 hour and 12 hour after irradiation the percentages of apoptosis cells in G-CSF group were (11.5 +/- 2.4)% and (15.5 +/- 3.3)%, respectively, which were significantly lower than that of the control group (16.5 +/- 2.2)% and (22.6 +/- 0.7)%, respectively (p < 0.05). The sjTREC copy amount was conspicuously higher in G-CSF group than that in the control at 30 day after irradiation (p < 0.01), but the preponderance disappeared 60 days later. It is concluded that G-CSF has a positive effect on the thymic cell cycle alteration to protect thymocytes from apoptosis and enhance the recent thymocyte emigration, which may contribute to the central immune reconstitution after irradiation. PMID- 22040992 TI - [PML-RARalpha and p21 are key factors for maintaining acute promyelocytic leukemia stem cells survival]. AB - Tumor stem/progenitor cells are the cells with the characteristics of self renewal, differentiating to all the other cell populations within tumor, which are also regarded as the source of tumor relapse, drug-resistance and metastasis. As a subtype of acute myeloid leukemia, acute promyelocytic leukemia (APL) represents the target of therapy due to the good response of the oncogenic protein PML-RARalpha to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). This review summarizes the latest research results of APL as follows: (1) there probably are two APL stem/progenitor cell populations within APL, and self renewal and survival of APL stem/progenitor cells highly depend on PML-RARalpha expression, cell cycle inhibitor p21, self-renewal associated molecules and chemokines; and (2) ATRA and ATO eradicate APL stem/progenitor cells mainly by PML-RARalpha degradation, FOXO3A activation and the inhibition of self-renewal associated signaling pathway of sonic hedgehog. These findings are helpful to improve other tumor therapy. PMID- 22040993 TI - [An update on epigenetic regulator gene mutations and pathogenesis of myelodysplastic syndromes]. AB - The myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disorders. So far, the etiology and pathogenesis of MDS is poorly understood. Recently, more and more epigenetic regulator gene such as TET2, ASXL1, EZH2, DNMT3A and UTX mutations were detected in patients with MDS: TET2 may convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC). TET2 is the most frequently mutated gene in MDS known so far and it may act as tumor-suppressor gene. ASXL1 belongs to the enhancer of trithorax and Polycomb (ETP) gene group. MDS phenotypes may be caused not only by loss-of-function of ASXL1 but also by gain-of-function mutations, overexpression of this gene and so on. EZH2 is a kind of histone methyltransferase. EZH2 is frequently over-expressed in a wide variety of cancerous tissue types, which reveals it has oncogenic activity. While, defined mutations resulted in dysfunction of histone methyltransferase activity, suggesting that EZH2 acts as a tumor suppressor for myeloid malignancies. DNMT3A belongs to the DNA methyltransferases (DNMT) gene family. It may be correlated with abnormal methylation status in patients with MDS. UTX coding protein is a histone demethylase, and UTX can affect cell proliferation as well as cell fate decision. Inactivating UTX mutations are found in multiple cancer types recently. These gene mutations may play key roles in the pathogenesis of MDS, which are summarized in this review. PMID- 22040994 TI - [Progress of studies on microenvironment of lymphoma]. AB - Many studies indicate that lymphoid neoplasms are related with chromosome translocations and the molecular alterations involving in the cell cycle and/or apoptotic pathways. However, survival of B and T tumor cells also depends on interactions of these cells with the accompanying cells comprising the lymphoma microenvironment. Immune cells, stromal cells and numerous molecular together make up the microenvironment and have functional interaction with tumor cells, promoting tumor growth and drug resistance. Different types of lymphoma have various clinical courses, therapy responses and prognoses, which show a close relationship with the microenvironment. This review summarizes several components of lymphoma microenvironment including macrophages, adhesion molecules and chemokines and the roles of microenvironment in classic non-Hodgkin's lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, suggesting that the microenvironment influence the prognosis of lymphoma, targeting microenvironment may be a potential method in lymphoma therapy. PMID- 22040995 TI - [Molecular mechanism of imatinib-induced thrombocytopenia in treatment of patients with CML]. AB - Imatinib mesylate has been commonly used in the treatment of patients with chronic myeloid leukemia (CML). However, a significant number of CML patients treated with imatinib developed thrombocytopenia. Platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor (PDGFR) plays a significant role in the regulation of thrombopoiesis. It is suggested that imatinib may block the PDGF/PDGFR and PI3-K/Akt pathway, then inducing the apoptosis of megakaryocytes and developing thrombocytopenia in these patients. In this review, the potential molecular mechanism of imatinib-induced thrombocytopenia in the treatment of CML patients is discussed, including imatinib and thrombocytopenia, PDGF/PDGFR and thrombopoiesis, potential mechanism of imatinib-induced thrombocytopenia in treatment of patients with CML and so on. PMID- 22040996 TI - [Current research advance on abnormalities of mesenchymal stem cells in hematological malignancies]. AB - Mesenchymal stem cells (MSC) have attracted high attention to their various origins, capability of multi-lineage differentiation, supporting hematopoiesis and regulating immunity. Consequently, MSC show great potential for tissue engineering and cell/gene therapy. The bone marrow microenvironment plays an important role in the pathogenesis of several hematological malignancies. It was confirmed that as key components of the hematopoietic microenvironment, MSC correlated complexly with tumor microenvironment. Recent reports showed that MSC from some patients with AML, MDS, ALL and MM harboured cytogenetic alterations. In addition, the phenotype, ability of differentiation and immunoregulatory function of MSC displayed different degree of abnormalities, suggesting that MSC played a role in the pathophysiological mechanism of malignant hematopoietic diseases. Besides, MSC have been found to participate in drug resistance of antileukemic therapy. Hematopoietic stem cell transplantation (HSCT) has become an important treatment approach for the malignant hematopoietic diseases in recent years. Because of the advantages of supporting hematopoiesis and regulating immunity, MSC are used to promote the engraftment and prophylaxis/treatment of GVHD. This review summarized briefly the abnormalities of mesenchymal stem cells in malignant hematological diseases and MSC research advances on cell therapy. PMID- 22040997 TI - [Influence of HLA-G on immunoregulatory function of human amniotic mesenchymal cells]. AB - Human leukocyte antigen G (HLA-G), a kind of non-classical major histocompatibility complex class I antigens, can inhibit inflammatory reaction, assist tumor cells to escape from immune surveillance and promote the immunologic tolerance of the graft. HLA-G, expressed and secreted by human amniotic mesenchymal cells (HAMC), suppresses the functions of NK cells, T cells and B cells and modulates the activity of dendritic cells (DC). These findings provide a theoretical basis for illustrating the mechanism of immunosuppression on HAMC. In this article, the recent advances on not only the gene and the molecular structure of HLA-G, but also the possible mechanisms of HLA-G in immunoregulatory function of HAMC, as well as the relation of HLA-G with HAMC, NK, DC, T and B cells are reviewed. PMID- 22040998 TI - [Progress of study on JAK2V617F mutation in myeloproliferative neoplasm]. AB - Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell diseases characterized by proliferation of one or more myeloid cell lineages in the bone marrow and increased mature and immature cells in peripheral blood. As the most important discovery in recent studies of MPN, JAk2V617F mutation is considered to closely relate with the pathogenesis of MPN. The mutated JAK2 lost self inhibition, and then, the sustained activation leads to a series of disorders in downstream signal transduction pathways, eventually resulting in malignant cell proliferation. A variety of methods have been used in quantitative/qualitative detection of JAK2V617F mutation, and researches about JAK2V617F mutation and its clinical features have also made some progress. However, it must be noted that there are still some unsolved problems, such as the role of JAk2V617F mutation in pathogenesis of MPN needs further exploration, effective targeted therapy for JAK2 is a attractive topic, and the application of JAK2V617F mutation in disease diagnosis also requires a deep research. In this review, the latest progress from different aspects is summarized briefly, including JAK2 and JAK2V617F mutation, effects of JAK2V617F mutation on the pathogenesis, clinical correlation of JAK2V617F with MPN, and targeting therapy. PMID- 22040999 TI - [Recent advances of studies on interaction of natural killer cells and fungi]. AB - Natural killer (NK) cells are important innate immune effector cells with broad applications in killing the tumor cells and pathogens due to its cytotoxicity without prior immune sensitization. Unfortunately, in humans, the activity of NK cells against fungi is poorly characterized. Insight progress in the fields of NK cells activating, pattern recognition receptors, signal modulating and correlated cell factors (IFN-gamma, GM-CSF, IL-10 and so on) has revolutionized understanding of the selective killing fungi by NK cells. Different morphotypes also can affect the immune status of NK cells. This article reviews the mechanism of fungi immune reaction, and the interaction between NK cells and fungi, and provides some new ideas for further study on pathogenesis of fungus and other infectious diseases and NK cell adoptively transferred immunotherapy. PMID- 22041000 TI - [New progress of study on labeling methods in vitro and distribution in vivo of mesenchymal stem cells]. AB - Mesenchymal stem cells (MSC) are a kind of non-hematopoietic adult stem cells with highly self-renewal and multilineage differentiation potential. Because MSC can be easily obtained and expanded in large amount in vitro, they have become a hot field of stem cell research in recent years. MSC as a seed carrier of cells and gene therapy have been widely used in cardiovascular, nervous, respiratory diseases, wound healing and other aspects in clinic. But some biological characteristics and the molecular control mechanisms of MSC are not very clear and need further explorations. The MSC isolated and cultured in vitro are a type of multipotent differentiation cells, which differentiation potential in vivo has still uncertained, the effectiveness and safety such as gene mutations and canceration in vivo remains to be explored. Deepgoing studys on homing characteristics, mechanisms and influence factors of MSC also contribute to the clinical application, and the studys on the MSC differentiation fate in microenvironment in vivo would be better for clinical application. So how stably and efficiently label MSC in vitro is the key problem to monitoring the survival, migration, distribution, proliferation and differentiation of MSC in vivo. This review summarizes the current progress of study on the new labeling methods in vitro of MSC, discussing the advantages and disadvantages of different in vitro labeling methods and application of appropriate conditions. PMID- 22041001 TI - The in vitro antimicrobial activity of natural infant fluoride-free toothpastes on oral micro-organisms. AB - PURPOSE: The objective of this study was to evaluate the antimicrobial activity of six toothpastes for infants: 3 fluoride-free experimental toothpastes--cashew based, mango-based and without plant extract and fluoride compared with 2 commercially fluoride-free toothpastes and 1 fluoridated toothpastes. METHODS: Six toothpastes for infants were evaluated in this study: (1) experimental cashew based toothpaste; (2) experimental mango-based toothpaste; (3) experimental toothpaste without plant extract and fluoride (negative control); (4) First Teeth brand toothpaste; (5) Weleda brand toothpaste; and (6) Tandy brand toothpaste (positive control). The antimicrobial activity was recorded against Streptococcus mutans, Streptococcus sobrinus, Lactobacillus acidophilus, and Candida albicans using the agar plate diffusion test. RESULTS: First Teeth, Weleda, mango-based toothpaste, and toothpaste without plant extract presented no antimicrobial effect against any of the tested micro-organisms. Cashew toothpaste had antimicrobial activity against S mutans, S sobrinus, and L acidophilus, but it showed no antimicrobial activity against C albicans. There was no statistical difference between the inhibition halo of cashew and Tandy toothpastes against S mutans and L acidophilus. CONCLUSIONS: Cashew fluoride-free toothpaste had inhibitory activity against Streptococcus mutans and Lactobacillus acidophilus, and these results were similar to those obtained for fluoridated toothpaste. PMID- 22041002 TI - Effective teaching of tooth-brushing to preschool children. AB - PURPOSE: The purpose of the present study was to compare artificial tooth brushing models (TBM) and individual modeling regarding their efficacy in teaching the correct brushing movements to younger preschool children. METHODS: A total of 141 30- to 50-month-old preschool children who had not been previously instructed on tooth-brushing were enrolled in the present trial. Four different model types/groups were compared: (1) giant TBM; (2) animal TBM puppet; (3) child him/herself in front of the mirror; (4) another person with the child in the mirror. Parameters of imitational learning were investigated by means of single person monitoring on the basis of a standardized observational method. The subjects were randomly assigned to 4 experimental groups, which were comparable regarding gender and age. Statistical analysis was performed using the chi square test. RESULTS: This study demonstrated that behavioral modeling types 3 and 4 were more suitable as a methodological basis than TBM. Correct tooth brushing position and movement were correlated with the attractiveness of the model and its similarity to the child. It was shown that human models achieved greatest learning success. CONCLUSION: It is important to find a "helper" and an attractive model person assisting in guiding the brush with a feedback in a mirror. PMID- 22041003 TI - Comparative study of 2 palatoplasty techniques to assess speech and fistula in primary cleft palate patients. AB - PURPOSE: To assess the Quality of speech and the incidence of post operative fistula in each technique after 6 months follow up study. METHODS: This prospective study consists of 24 patients in the age group of 18 to 36 months, male 12 and female 12. All the patients were divided into two groups-Group I-12 patients for two layer closure, Group II-12 patients for three layer closure. Exclusion criteria was submucous clefts, any identified syndrome and patients with hearing loss. All the patients have undergone pre-operative speech assessment by the speech therapist. At end of 6 months, speech analysis was done based on three parameters, i.e. nasality (A), Articulation (B) and intelligibility (C). RESULTS: Patients with radical muscle dissection (three layer) group had statistically significant (P=0.023) improvement in nasal resonance compared to the conservative technique (two layer) in the younger age group. But there was no statistically significant difference in the articulation and the intelligibility of speech. CONCLUSION: Radical dissection and palatal muscle reconstruction confers better functional results regarding nasal resonanace, especially in younger age group. Quality of speech in the elder group, patients 25-36 months old in both the technique groups was almost the same. The incidence of fistula was slightly more in the radical dissection group. PMID- 22041004 TI - Transmigration of mandibular canines: a rare case report and review of literature. AB - Transmigration of permanent mandibular canines is a very rare phenomenon and has no definite etiology. Most of them are asymptomatic, impacted, and commonly involve the left canines. The eruption of transmigrated canines is even rarer. The purpose of this paper was to review the literature on erupted transmigrated mandibular canines and report a rare case of it in a 13-year-old girl with a transmigrated permanent right canine corresponding to the least frequent Mupparapu type 5 pattern. PMID- 22041005 TI - Current status of nitrous oxide as a behavior management practice routine in pediatric dentistry. AB - Nitrous oxide (N(2)O) as a behavioral management intervention in children has attained an excellent safety record and is, therefore, used widely. As is true of any diagnostic or therapeutic dental intervention, however, its usage merits periodic review, even if-or particularly when-it is routinely applied. For example, when N(2)O is used in combination with other sedatives, such polypharmacy can produce potentially serious side effects. There are also bioenvironmental risks to patients and staff if ambient air is not properly monitored. Using historical publications, current empirical articles, professional usage policies, and educational textbooks, the purpose of this article was to review indications and contraindications of N(2)O and discuss various factors that should or should not be considered about its use in the United States. Even though today's parents may be more accepting of pharmacologic approaches such as N(2)O, the choice to use it should always be made with the child's best interest in mind. PMID- 22041006 TI - In vivo comparison of reduction in bacterial count after caries excavation with 3 different techniques. AB - PURPOSE: The purpose of this in vivo study was to evaluate and compare the reduction in bacterial count in dentin after caries excavation with a spoon excavator, carbide bur, and polymer bur. METHODS: Forty-five primary molar teeth from 36 children with occlusal dentinal carious lesions without pulpal involvement were chosen and divided into 3 groups: (1) caries was excavated using a brand new round bur with a slow-speed handpiece at 800 rpm from the occlusal aspect; (2) new polymer burs were used with slow-speed handpiece at 800 rpm, according to the lesion's size; (3) caries was excavated using a sterile spoon excavator. RESULTS: The mean difference in colony forming units of Streptococcus mutans and lactobacilli before and after caries excavation was found to be significant (P<.01) in all 3 groups. Further intergroup comparison of percentage reduction in bacterial counts between different groups was statistically significant, except when the percentage reduction in S mutans of group 2 was compared to that of group 3 (P=.26). Reduction in S mutans count was highly significant (P<.001) for group 1 vs group 3. CONCLUSIONS: Caries removal with a carbide bur, polymer bur, and spoon excavator produced significant reduction in viable count of both Streptococcus mutans and lactobacilli. Carbide burs, however, produced greater reduction in the viable count of bacteria followed by polymer bur and spoon excavator. PMID- 22041007 TI - Use of dental care and prevalence of caries among immigrant and Spanish-born children. AB - PURPOSE: The purpose of this paper was to describe the use of dental services and the prevalence of dental caries in children living in Madrid, Spain. METHODS: A descriptive, cross-sectional study was conducted using data from the Madrid City Health Survey. The questions asked were: (1) When was the last time your child visited the dentist? (2) What was the reason for your child's last visit? and (3) Is your child currently suffering from caries, fillings, or bleeding from the gums when brushing? The independent variables included: sex; age; education level; and nationality. RESULTS: Data from 960 children (approximately 27% of whom were immigrants) were analyzed. Over the last year, approximately 59% of the children had received dental care and 28% suffered from caries. After multivariate analysis, we observed that 3- to 6-year-old children, immigrants, and children of parents with low education levels are more likely not to have received dental care during the last year. We also found that children are more likely to suffer from caries as they get older and if they are immigrants. CONCLUSIONS: Being an immigrant and from a lower education level typically results in a less frequent use of dental health services, and children of immigrants have a greater risk of suffering from dental caries. It is essential to investigate the reasons why and introduce strategies to reduce barriers to dental health access among immigrants. PMID- 22041008 TI - Remineralization of primary tooth enamel from individuals with Down syndrome. AB - PURPOSE: The purpose of this study was to clarify the characteristics of primary tooth enamel of Down syndrome patients (DSPs). We examined 9 primary teeth of Down syndrome children and 11 primary teeth of normally developed children to investigate the remineralization processes of enamel by transverse microradiography and X ray micro analyzer (XMA). METHODS: Mineral loss, lesion depth, maximum mineral value, minimum mineral value, depth of maximum mineral value, and depth of minimum mineral value were used to analyze transverse microradiography (TMR). In addition, we calculated the percentage of enamel remineralization. RESULTS: All the parameters in the 2 groups showed marked recovery. The results indicated that the Down syndrome group was significantly remineralized the same way as the control group. According to the comparison of mineral content distribution by XMA, the content distribution of magnesium was different between the 2 groups. CONCLUSION: While recovery through remineralization of primary teeth was similar between Down syndrome children and normally developed children, the mechanism of remineralization process may be different between the 2 groups; consequently, magnesium may be considered as one of the factors affecting recovery. PMID- 22041009 TI - Wiscott Aldrich syndrome with oral involvement: a case report. AB - Wiskott Aldrich syndrome is an X-linked recessive disorder characterized by thrombocytopenia with microplatelets, eczema, recurrent infections, and predisposition to autoimmune disease and malignancy. It is a rare syndrome, and the incidence rate is approximately 4 in every 1 million live male births with no clear ethnic or racial predilection. The purpose of this paper was to report a case of Wiskott Aldrich syndrome with oral involvement demonstrated by 2 male siblings. PMID- 22041010 TI - Oligodontia associated with osteopetrosis: a rare case report. AB - Osteopetrosis is a descriptive term that refers to a group of rare hereditary disorders of the skeleton characterized by increased density of the bones. It was first described in 1904 by Albers-Schonberg, a German radiologist. This disease varies greatly in its presentation and severity ranging from neonatal onset with life threatening conditions such as bone marrow failure to incidental finding of osteopetrosis on radiographs. Dental abnormality may be attributed to pathological changes in the bone. Dentists should be aware of patients with the disease because of its effect on osteoclast function which results in impaired wound healing. This paper presents the case of a five-year-old girl exhibiting oligodontia associated with osteopetrosis. PMID- 22041011 TI - Complications of surgical extraction of ankylosed primary teeth and distal shoe space maintainers. AB - The purpose of this report was to present the iatrogenic complications that may result from the management of ankylosed primary teeth as well as describe the case of a patient with an ankylosed primary mandibular left second molar which was surgically extracted and an adjacent primary first molar that was cemented with a distal shoe space maintainer. Aggressive surgical removal of the ankylosed tooth caused damage to the developing crown of the successor. Improper placement of the appliance caused perforation of the developing tooth follicle. Orthodontic therapy and a polycarbonate temporary crown were used to restore occlusion. Nonsurgical extractions and alternative appliances should be considered when treating patients with ankylosed primary second molars. PMID- 22041012 TI - Mandibular buccal bifurcation cyst: a case report and literature review. AB - The mandibular buccal bifurcation cyst is a cystic lesion occurring on the buccal surface of the permanent mandibular first molar in 6- to 8-year-old children. The purpose of this article was to present a case report of an 8-year-old with a radiolucent area on the permanent mandibular left first molar, with clinical, radiological, and histological characteristics compatible with the pathological entity mentioned. The treatment adopted in this case was enucleation without extraction. The patient is still under observation without any sign of recurrence. PMID- 22041013 TI - Root canal treatment of an immature dens invaginatus with apical periodontitis: a case report. AB - The purpose of this paper was to describe the case of an 11-year-old patient who presented a dens invaginatus, detected in the permanent maxillary left lateral incisor, with an immature open apex and extensive apical periodontitis and sinus tract. The mineralized invaginated barrier was removed, and a nonsurgical root canal treatment was performed using both calcium hydroxide as a root canal dressing to stimulate apexification and a mineral trioxide aggregate (MTA) plug to permit root canal filling. After a 14-month period of root canal dressing changes, no evidence of apical periodontitis was observed, and the MTA plug was placed in the root canal's apical portion. The root canal filling was performed using the thermoplasticized gutta-percha technique. At the 12-month follow-up, complete radiographic periapical healing, characterized by bone formation in the area around the tooth apex, and no clinical or radiographic evidence of refractory apical periodontitis were detected. PMID- 22041014 TI - Unusual dens evaginatus on maxillary premolars: a case report. AB - Dens evaginatus is a developmental anomaly that can be defined as a tubercle from the surface of an affected tooth. It is composed of enamel and dentin usually enclosing pulp tissue. It is a rare dental anomaly commonly seen on premolars. A 12-year-old boy reported for the management of dental caries. He had bilateral occurrence of dens evaginatus on maxillary second premolars. The tubercle on the right side was unusually long without occlusal interference with the opposing primary mandibular second molar. Carious teeth were restored and the tubercle was left untreated. Management of dens evaginatus is determined by various factors which are discussed in decision-support system. Pulpal complication due to caries or fracture of tubercle can occur; hence it should be periodically monitored. PMID- 22041015 TI - Agenesis of permanent mandibular anterior teeth: a case report. AB - Tooth agenesis is one of the common congenital anomalies seen in humans. Hypodontia is the congenital absence of 1 or a few teeth only, with a prevalence of approximately 2% to 10% in the permanent dentition. The number of patients exhibiting congenitally missing mandibular incisors is low, with a prevalence rate of less than 1% observed. The purpose of this paper was to report a case of congenitally missing permanent mandibular incisors and canines in a 10-year-old girl. PMID- 22041016 TI - 1alpha,25-Dihydroxyvitamin D3 inhibits osteoblastic differentiation of mouse periodontal fibroblasts. AB - OBJECTIVE: Periodontal ligament (PDL) is a non-mineralized tissue connecting cementum and alveolar bone. Recent studies have suggested that periodontal fibroblasts can differentiate into mineralized tissue-forming cells such as osteoblasts and cementoblasts. We elucidated the immunolocalization of vitamin D receptor (VDR) and the effects of vitamin D(3) (VD(3)) on mouse periodontal fibroblasts to clarify the role of VDR and VD(3) in the differentiation of periodontal fibroblasts. DESIGN: Immunohistochemical analysis using anti-VDR antibody was performed in paraffin sections of mouse mandibles at E13, E14, E17, P10, and P35. The roles of VD(3) in osteoblastic differentiation and mineralization were estimated by alkaline phosphatase (ALP) and alizarin red (AR) staining. In addition, the mRNA expression of osteoblast markers and mineralization inhibitors was examined by real-time PCR. RESULTS: At the bud, cap and early bell stages, immunoreactivity for VDR was scarcely seen in the cells of dental follicles. Labelling was detected in the nuclei of cemetoblasts, periodontal fibroblasts and osteoblasts during root formation. VD(3) inhibited ALP activity and AR-positive mineralized nodule formation of periodontal fibroblasts in osteogenic culture medium. Real-time PCR revealed that VD(3) down regulated the levels of osteoblast markers. In contrast, VD(3) significantly up regulated the level of periodontal ligament associated protein (PLAP)-1, a negative regulator of osteoblastic differentiation. CONCLUSION: These results suggest that VD(3) negatively regulates the osteoblastic differentiation of mouse periodontal fibroblasts and prevents the periodontal ligament from mineralization via increase of PLAP-1. PMID- 22041017 TI - Association of interferon-gamma gene polymorphisms with susceptibility to oral lichen planus in the Thai population. AB - OBJECTIVE: Interferon-gamma (IFN-gamma) is highly expressed in oral lichen planus (OLP). The IFN-gamma (+874 in intron 1, rs2430561) TT genotype, which has been reported to be associated with high IFN-gamma production, was hypothesized to be associated with susceptibility to OLP in the Thai population. DESIGN: Genomic DNA samples from 74 OLP and 268 healthy controls were evaluated for IFN-gamma polymorphisms by polymerase chain reaction with sequence-specific primers (PCR SSP) and direct sequencing method. RESULTS: The T allele was significantly associated with an increased risk of OLP development as compared to the A allele (OR=1.76, P=0.004; P(c)=0.02). The effect of the T allele was similar to an autosomal recessive disorder; the presence of TT genotype (when compared to AA and AT) conferred an OR of 2.61, P=0.008; P(c)=0.04. CONCLUSIONS: We found an association between IFN-gamma +874A/T polymorphism and susceptibility to OLP. However, an association study utilising a larger sample size and patients from other races apart from the Asian population should be performed to further verify these findings. PMID- 22041018 TI - Recombinant bone morphogenetic protein-2 induces up-regulation of vascular endothelial growth factor and interleukin 6 in human pre-osteoblasts: role of reactive oxygen species. AB - OBJECTIVE: Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) have been reported in many studies to play a major role in the communication between endothelial cells and osteoblasts. The inflammatory reaction and relative hypoxia at the site of bone injury are the first stages of the fracture repair. rhBMP-2 has been used extensively in spinal fusion and reconstruction of maxillofacial bone defects with main complication is the formation of seroma. The aim of this study was to test whether rhBMP-2 regulates the expression of the angiogenic and inflammatory mediators in pre-osteoblasts via generating reactive oxygen species (ROS). METHODS: rhBMP-2 effect on angiogenesis and inflammatory genes was assessed using normal human osteoblasts (NHOst). Angiogenesis genes were measured using angiogenic PCR array. VEGF and IL6 production were analysed using ELISA kit and real-time PCR. ROS production was assessed using dihydroethidine and dichlorofluorescein staining and lipid peroxidation. HIF-1alpha immunoreactivity was performed using immunofluorescence staining. RESULTS: There was an increase in the pro-angiogenic and -inflammatory genes as well as VEGF and IL6 protein expression in NHOst by rhBMP-2. This increase in VEGF and IL6 was blocked by the ROS scavenger N-acetyl cysteine (NAC). CONCLUSION: The regulatory effect of rhBMP-2 on angiogenesis and inflammation is mediated through a ROS-dependent mechanism, which involves upregulation of crucial angiogenic and inflammatory mediators such as VEGF and IL6. These findings highlight the need for future studies to identify new therapeutic targets downstream from rhBMP-2 to potentiate its beneficial effect or limit its complications such as seroma formation. PMID- 22041019 TI - Demineralised human dentine matrix stimulates the expression of VEGF and accelerates the bone repair in tooth sockets of rats. AB - OBJECTIVE: In this study we investigated the possible use of human demineralised dentine matrix (DHDM), obtained from the extracted teeth, as bone graft material and evaluated the expression of vascular endothelial growth factor (VEGF) induced by this material in the healing process of tooth sockets of rats. DESIGN: To evaluate bone regeneration and expression of VEGF induced by DHDM, thirty-two male Wistar rats weighing approximately 200 g were used. After maxillary second molar extraction, the left sockets were filled with DHDM and the right sockets were naturally filled by blood clot (control). The animals were sacrificed at 3, 7, 14 and 21 days after surgery and upper maxillaries were processed for histological, morphometric and immunohistochemical analyses. DHDM was used to evaluate the mechanical effect of bone graft material into sockets. Expression of VEGF was determined by immunohistochemistry in all groups. RESULTS: Our results demonstrated a significant increase in the newly formed bone tissue in sockets of 7, 14 and 21 days and a significant increase in VEGF expression at days 7 and 14 on treated sockets. CONCLUSIONS: Our results showed that DHDM increases the expression of VEGF and accelerates the healing process in rats tooth sockets, by stimulating bone deposition and also vessels formation. These results suggest that DHDM has osteoinductive/osteoconductive potential and may represent an efficient grafting material on guided bone regeneration. PMID- 22041020 TI - Changes in condylar cartilage after anterior mandibular displacement in juvenile pigs. AB - Adaptive remodelling of the mandibular condyle in response to mandibular advancement is the mechanism exploited by orthodontic forward displacement devices. OBJECTIVE: This work investigated the expression of collagens, matrix metalloproteinases and vascular endothelial growth factor during this process. DESIGN: Twenty juvenile pigs were randomly divided into two experimental groups, where the treatment group was fitted with mandibular advancement splints, and the control group was not. Changes in the mRNA content of condylar cartilage tissue was then were measured by real-time PCR using specific primers after 4weeks of treatment. RESULTS: The temporal pattern of the expression of Col1 and MMP13 during condylar adaptation coincided with that during natural condylar growth. The amount of the expression of Col10 during condylar adaptation was significantly lower (p<0.05), whereas the expression of Col2, MMP8 and VEGF was significantly higher compared to natural growth (p<0.05). CONCLUSIONS: It is suggested that condylar adaptation in growing pigs triggered by mandibular forward positioning results not only from passive adaptation of cartilage, but also involves growth affected processes. Our results showed that mechanical strain produced by mandibular advancement induced remodelling and revascularization in the posteriocranial mandibular condyle. These results are mostly consistent with former published histological and histomorphometrical analyses. PMID- 22041021 TI - An in vitro investigation of Lactococcus lactis antagonizing cariogenic bacterium Streptococcus mutans. AB - OBJECTIVES: The present study tested the antagonism between Lactococcus lactis and Streptococcus mutans and evaluated the feasibility of the application of L. lactis for the inhibition of S. mutans in the oral cavity. METHODS: Competition assays on plates were employed to determine whether L. lactis antagonises S. mutans under different nutritional conditions, and real-time reverse transcriptase PCR was used to evaluate the effects of metabolites of S. mutans on the bacteriocin nisin genes in L. lactis. Furthermore, the colonisation and effects of L. lactis on the surface of a tooth were examined by scanning electron microscopy. RESULTS: L. lactis competitively inhibited S. mutans growth under nutritional deficiency, and the metabolites of S. mutans, including several exogenous molecular signals, enhanced the expression of genes related to nisin synthesis, nisA, nisB and nisI. Additionally, L. lactis effectively colonised the surface of tooth enamel, which showed substantially less decay with L. lactis adhesion compared to S. mutans adhesion. CONCLUSIONS: These findings suggest avenues of research into a new strategy to reduce major cariogenic S. mutans adhesion on the surfaces of teeth. PMID- 22041022 TI - In situ remineralisation of eroded enamel lesions by NaF rinses. AB - OBJECTIVE: The purpose of this pilot study was to evaluate the remineralisation of eroded enamel by NaF rinses in an intra-oral model. METHODS: Serving as their own control, subjects (N=80) participated in a randomised, four-leg (20 subjects/leg), 28-day, parallel design study. In each leg, each participant wore a customised orthodontic bracket attached to a mandibular molar that contained one tooth block having an initial erosive lesion (0.3% citric acid, pH 3.75, 2 h). Within the 28-day period, participants engaged in twice-daily brushing for 1 min with a fluoride-free dentifrice followed by 1-min rinsing with one of the following aqueous rinses: fluoride-free (0 ppm F), 225 ppm F, 225 ppm F plus functionalised beta-tricalcium phosphate (fTCP), and 450 ppm F. Following intra oral exposure, appliances were removed and specimens were analysed using surface microhardness (SMH) and transverse microradiography (TMR). RESULTS: Statistically significant (p<0.05) remineralisation, as determined by SMH and TMR, of the eroded enamel relative to baseline occurred for each fluoride system. No significant differences in SMH were observed amongst the fluoride groups (p>0.05), however, 225 ppm plus fTCP produced 27% and 7% SMH indent length reduction relative to 225 ppm F and 450 ppm F, respectively. No significant differences in TMR were observed amongst the fluoride groups (p>0.05), however, 225 ppm F plus fTCP and 450 ppm F produced significant (p<0.05) mineral gains relative to the fluoride-free control, whilst 225 ppm F did not (p>0.05). Relative to the 225 ppm F group, the 450 ppm F and 225 ppm F plus fTCP groups produced 65% and 61% greater mineral change, respectively. CONCLUSIONS: These pilot results demonstrate this model is sensitive to fluoride and that addition of fTCP to an aqueous rinse containing 225 ppm F may provide significant remineralisation benefits. Therefore, the combination of relatively low levels of fluoride and fTCP might be an effective alternative to a high fluoride treatment for anti-erosion benefits. PMID- 22041023 TI - In vitro repair of DNA hairpins containing various numbers of CAG/CTG trinucleotide repeats. AB - Expansion of CAG/CTG trinucleotide repeats (TNRs) in humans is associated with a number of neurological and neurodegenerative disorders including Huntington's disease. Increasing evidence suggests that formation of a stable DNA hairpin within CAG/CTG repeats during DNA metabolism leads to TNR instability. However, the molecular mechanism by which cells recognize and repair CAG/CTG hairpins is largely unknown. Recent studies have identified a novel DNA repair pathway specifically removing (CAG)(n)/(CTG)(n) hairpins, which is considered a major mechanism responsible for TNR instability. The hairpin repair (HPR) system targets the repeat tracts for incisions in the nicked strand in an error-free manner. To determine the substrate spectrum of the HPR system and its ability to process smaller hairpins, which may be the intermediates for CAG/CTG expansions, we constructed a series of CAG/CTG hairpin heteroduplexes containing different numbers of repeats (from 5 to 25) and examined their repair in human nuclear extracts. We show here that although repair efficiencies differ slightly among these substrates, removal of the individual hairpin structures all involve endonucleolytic incisions within the repeat tracts in the nicked DNA strand. Analysis of the repair intermediates defined specific incision sites for each substrate, which were all located within the repeat regions. Mismatch repair proteins are not required for, nor do they inhibit, the processing of smaller hairpin structures. These results suggest that the HPR system ensures CAG/CTG stability primarily by removing various sizes of (CAG)(n)/(CTG)(n) hairpin structures during DNA metabolism. PMID- 22041024 TI - Trypanosoma brucei AP endonuclease 1 has a major role in the repair of abasic sites and protection against DNA-damaging agents. AB - DNA repair mechanisms guarantee the maintenance of genome integrity, which is critical for cell viability and proliferation in all organisms. As part of the cellular defenses to DNA damage, apurinic/apyrimidinic (AP) endonucleases repair the abasic sites produced by spontaneous hydrolysis, oxidative or alkylation base damage and during base excision repair (BER). Trypanosoma brucei, the protozoan pathogen responsible of human sleeping sickness, has a class II AP endonuclease (TBAPE1) with a high degree of homology to human APE1 and bacterial exonuclease III. The purified recombinant enzyme cleaves AP sites and removes 3' phosphoglycolate groups from 3'-ends. To study its cellular function, we have established TBAPE1-deficient cell lines derived from bloodstream stage trypanosomes, thus confirming that the AP endonuclease is not essential for viability in this cell type under in vitro culture conditions. The role of TBAPE1 in the removal of AP sites is supported by the inverse correlation between the level of AP endonuclease in the cell and the number of endogenously generated abasic sites in its genomic DNA. Furthermore, depletion of TBAPE1 renders cells hypersensitive to AP site and strand break-inducing agents such as methotrexate and phleomycin respectively but not to alkylating agents. Finally, the increased susceptibility that TBAPE1-depleted cells show to nitric oxide suggests an essential role for this DNA repair enzyme in protection against the immune defenses of the mammalian host. PMID- 22041027 TI - Proline accumulation in baker's yeast enhances high-sucrose stress tolerance and fermentation ability in sweet dough. AB - During bread-making processes, yeast cells are exposed to various baking associated stresses. High-sucrose concentrations exert severe osmotic stress that seriously damages cellular components by generation of reactive oxygen species (ROS). Previously, we found that the accumulation of proline conferred freeze thaw stress tolerance and the baker's yeast strain that accumulated proline retained higher-level fermentation abilities in frozen doughs than the wild-type strain. In this study, we constructed self-cloning diploid baker's yeast strains that accumulate proline. These resultant strains showed higher cell viability and lower intracellular oxidation levels than that observed in the wild-type strain under high-sucrose stress condition. Proline accumulation also enhanced the fermentation ability in high-sucrose-containing dough. These results demonstrate the usefulness of proline-accumulating baker's yeast for sweet dough baking. PMID- 22041025 TI - XRCC1 and base excision repair balance in response to nitric oxide. AB - Inflammation associated reactive oxygen and nitrogen species (RONs), including peroxynitrite (ONOO(-)) and nitric oxide (NO), create base lesions that potentially play a role in the toxicity and large genomic rearrangements associated with many malignancies. Little is known about the role of base excision repair (BER) in removing these endogenous DNA lesions. Here, we explore the role of X-ray repair cross-complementing group 1 (XRCC1) in attenuating RONs induced genotoxicity. XRCC1 is a scaffold protein critical for BER for which polymorphisms modulate the risk of cancer. We exploited CHO and human glioblastoma cell lines engineered to express varied levels of BER proteins to study XRCC1. Cytotoxicity and the levels of DNA repair intermediates (single strand breaks; SSB) were evaluated following exposure of the cells to the ONOO(-) donor, SIN-1, and to gaseous NO. XRCC1 null cells were slightly more sensitive to SIN-1 than wild-type cells. We used small-scale bioreactors to expose cells to NO and found that XRCC1-deficient CHO cells were not sensitive. However, using a molecular beacon assay to test lesion removal in vitro, we found that XRCC1 facilitates AAG-initiated excision of two key NO-induced DNA lesions: 1,N(6) ethenoadenine and hypoxanthine. Furthermore, overexpression of AAG rendered XRCC1 deficient cells sensitive to NO-induced DNA damage. These results show that AAG is a key glycosylase for BER of NO-induced DNA damage and that XRCC1's role in modulating sensitivity to RONs is dependent upon the cellular level of AAG. This demonstrates the importance of considering the expression of other components of the BER pathway when evaluating the impact of XRCC1 polymorphisms on cancer risk. PMID- 22041028 TI - P-selectin glycoprotein ligand-1 deficiency leads to cytokine resistance and protection against atherosclerosis in apolipoprotein E deficient mice. AB - Adhesive interactions between endothelial cells and leukocytes contribute to atherosclerotic plaque growth. However, mechanism(s) responsible for endothelial priming and deactivation in inflammatory diseases such as atherosclerosis are not clear. Apolipoprotein E deficient mice were generated with deficiency of P selectin glycoprotein ligand-1 (Psgl-1(-/-), ApoE(-/-)). On both standard chow and Western diet, Psgl-1(-/-), ApoE(-/-) mice were protected against atherosclerosis compared to Psgl-1(+/+), ApoE(-/-) controls. Psgl-1(-/-), ApoE(-/ ) mice also showed reduced leukocyte rolling and firm attachment on endothelial cells, however, adoptively transferred Psgl-1(+/+), ApoE(-/-) leukocytes into Psgl-1(-/-), ApoE(-/-) hosts displayed similar reduced rolling as Psgl-1(-/-), ApoE(-/-) leukocytes. Hematopoietic deficiency of Psgl-1 conferred resistance to the effects of interleukin-1beta (IL-1beta) on leukocyte rolling along with reduced circulating levels of sP-sel and sE-sel. Antibody blockade of Psgl-1 also reduced endothelial activation in response to IL-1beta, eliminated leukocyte rolling, and was protective against atherosclerosis in ApoE(-/-) mice. Monocyte depletion with clodronate restored the endothelial response to IL-1beta in Psgl 1(-/-) mice. This study suggests that Psgl-1 deficiency leads to reduced atherosclerosis and adhesive interactions between endothelial cells and leukocytes by indirectly regulating endothelial responses to cytokine stimulation. PMID- 22041029 TI - Survivin expression induced by endothelin-1 promotes myofibroblast resistance to apoptosis. AB - Fibrosis of the lungs and other organs is characterized by the accumulation of myofibroblasts, effectors of wound-repair that are responsible for the deposition and organization of new extracellular matrix (ECM) in response to tissue injury. During the resolution phase of normal wound repair, myofibroblast apoptosis limits the continued deposition of ECM. Mounting evidence suggests that myofibroblasts from fibrotic wounds acquire resistance to apoptosis, but the mechanisms regulating this resistance have not been fully elucidated. Endothelin 1 (ET-1), a soluble peptide strongly associated with fibrogenesis, decreases myofibroblast susceptibility to apoptosis through activation of phosphatidylinositol 3'-OH kinase (PI3K)/AKT. Focal adhesion kinase (FAK) also promotes myofibroblast resistance to apoptosis through PI3K/AKT-dependent and independent mechanisms, although the role of FAK in ET-1 mediated resistance to apoptosis has not been explored. The goal of this study was to investigate whether FAK contributes to ET-1 mediated myofibroblast resistance to apoptosis and to examine potential mechanisms downstream of FAK and PI3K/AKT by which ET-1 regulates myofibroblast survival. Here, we show that ET-1 regulates myofibroblast survival by Rho/ROCK-dependent activation of FAK. The anti-apoptotic actions of FAK are, in turn, dependent on activation of PI3K/AKT and the subsequent increased expression of Survivin, a member of the inhibitor of apoptosis protein (IAP) family. Collectively, these studies define a novel mechanism by which ET-1 promotes myofibroblast resistance to apoptosis through upregulation of Survivin. PMID- 22041031 TI - [Metabolically active volumes automatic delineation methodologies in PET imaging: review and perspectives]. AB - PET imaging is now considered a gold standard tool in clinical oncology, especially for diagnosis purposes. More recent applications such as therapy follow-up or tumor targeting in radiotherapy require a fast, accurate and robust metabolically active tumor volumes delineation on emission images, which cannot be obtained through manual contouring. This clinical need has sprung a large number of methodological developments regarding automatic methods to define tumor volumes on PET images. This paper reviews most of the methodologies that have been recently proposed and discusses their framework and methodological and/or clinical validation. Perspectives regarding the future work to be done are also suggested. PMID- 22041032 TI - PARTNER B: where will it take us? AB - PARTNER trial, cohort B has taken our cardiovascular community to new heights in multidisciplinary collaboration while raising awareness in the primary care community regarding the shortcomings of noninterventional treatment of symptomatic AS. With a rate of death from any cause at 1 year that is 20% lower with transcatheter aortic valve replacement (TAVR) in comparison with standard medical therapy, TAVR should be considered the new standard of care for patients with AS who are not suitable candidates for surgery. Despite TAVR's initial success, this landmark trial leaves questions about durability, paravalvular regurgitation, and procedural complications unanswered. Nonetheless, TAVR is clearly and unequivocally a new and successful treatment for symptomatic AS. Complication rates in this early stage of experience with a first-generation device are much lower than many had expected, and will not prevent TAVR from moving steadily down the risk spectrum. PMID- 22041033 TI - Is the predictive ability of positron emission tomography after neoadjuvant treatment for esophageal cancer ready for prime-time? AB - Monjazeb et al performed a single-institution, retrospective study of 163 patients with histologically confirmed stage I to IVa esophageal cancer to assess the utility of positron-emission tomography (PET) in delineating which patients would most likely benefit from esophagectomy after induction chemoradiation therapy. They found that patients who achieve a PET complete response after definitive chemoradiation therapy had similar outcomes to patients treated with trimodal therapy and concluded that patients who achieve a PET complete response after induction therapy may not benefit from esophagectomy. Though their study is interesting, their results should be validated by a prospective trial before they are incorporated into clinical practice. PMID- 22041034 TI - Retrieval practice as a means of primary learning: Socrates had the right idea. AB - In a recent publication, investigators examined the ways in which learners most effectively acquired new knowledge. The authors found that students achieved the most meaningful and long-lasting learning through retrieval practice, a method consisting of taking tests on the curricular material covered as part of the primary learning activity. The findings from this study may be useful in enhancing the ways that we prepare our surgical trainees. Further, these data have important implications as we consider our own processes for lifelong learning. PMID- 22041035 TI - Increasing the lung donor pool: recruitment of the gift of life. AB - Lungs suitable for organ donation are a scarce resource. Recent efforts with alternative ventilatory strategies have yielded promise to the potential expansion of lungs suitable for transplantation. PMID- 22041030 TI - Computational analysis of expression of human embryonic stem cell-associated signatures in tumors. AB - BACKGROUND: The cancer stem cell model has been proposed based on the linkage between human embryonic stem cells and human cancer cells. However, the evidences supporting the cancer stem cell model remain to be collected. In this study, we extensively examined the expression of human embryonic stem cell-associated signatures including core genes, transcription factors, pathways and microRNAs in various cancers using the computational biology approach. RESULTS: We used the class comparison analysis and survival analysis algorithms to identify differentially expressed genes and their associated transcription factors, pathways and microRNAs among normal vs. tumor or good prognosis vs. poor prognosis phenotypes classes based on numerous human cancer gene expression data. We found that most of the human embryonic stem cell- associated signatures were frequently identified in the analysis, suggesting a strong linkage between human embryonic stem cells and cancer cells. CONCLUSIONS: The present study revealed the close linkage between the human embryonic stem cell associated gene expression profiles and cancer-associated gene expression profiles, and therefore offered an indirect support for the cancer stem cell theory. However, many interest issues remain to be addressed further. PMID- 22041036 TI - Surgical resection or stereotactic body radiation therapy in elderly patients with early-stage lung cancer: evolving treatment algorithms and a call for reliable comparisons. AB - David Palma and colleagues report on the impact of stereotactic body radiation therapy (SBRT) on treatment patterns of elderly patients in the Netherlands. This study, published recently in the Journal of Clinical Oncology, is a retrospective review of data collected by the Amsterdam Cancer Registry. This study highlights many of the difficulties encountered when comparing the effectiveness of surgical resection and SBRT. PMID- 22041037 TI - Killing two birds with one salicylate: aspirin's dual roles in preventative health. AB - In a recent article published in The Lancet, investigators studied the impact of daily aspirin use on subsequent cancer deaths. Utilizing data from more than 25,000 patients enrolled in 8 large trials, which were originally intended to study the impact of daily aspirin use on the incidence of cardiovascular events, the authors found a substantial decrease in risk of fatal solid organ malignancies. In particular, the risk reduction was specific to adenocarcinomas. The findings from this study are highly relevant to the thoracic surgeon, with adenocarcinomas of the lung and esophagus among those tumors demonstrating the most profound risk reduction. PMID- 22041038 TI - The SYNTAX score and SYNTAX-based clinical risk scores. AB - Risk stratification is an important and essential component in appropriately informing patients electing to undergo coronary artery bypass graft or percutaneous coronary intervention. This process is an integral part of the SYNTAX pioneered Heart Team approach in selecting the most appropriate revascularization modality in patients with complex coronary artery disease. The SYNTAX score was pioneered as an anatomical-based risk score that aided in this decision-making process. The purpose of this review is to examine the SYNTAX score and subsequent risk models that have been developed on the basis of this landmark anatomical-based risk score. PMID- 22041039 TI - Quantitation of mitral regurgitation. AB - Mitral regurgitation (MR) is the most frequent valve disease. Nevertheless, evaluation of MR severity is difficult because standard color flow imaging is plagued by considerable pitfalls. Modern surgical indications in asymptomatic patients require precise assessment of MR severity. MR severity assessment is always comprehensive, utilizing all views and methods. Determining trivial/mild MR is usually easy, based on small jet and flow convergence. Specific signs of severe MR (pulmonary venous flow systolic reversal or severe mitral lesion) are useful but insensitive. Quantitative methods, quantitative Doppler (measuring stroke volumes) and flow convergence (aka PISA method), measure the lesion severity as effective regurgitant orifice (ERO) and volume overload as regurgitant volume (RVol). Interpretation of these numbers should be performed in context of specific MR type. In organic MR (intrinsic valve lesions) ERO >= 0.40 cm(2) and RVol >= 60 mL are associated with poor outcome, while in functional MR ERO >= 0.20 cm(2) and RVol >= 30 mL mark reduced survival. While MR assessment should always be comprehensive, quantitative assessment of MR provides measures that are strongly predictive of outcome and should be the preferred approach. The ERO and RVol measured by these methods require interpretation in causal context to best predict outcome and determine MR management. PMID- 22041040 TI - The Ross procedure: state of the art 2011. AB - The purpose of this paper is to review the current literature and practice of the Ross concept of using the autologous pulmonary valve to replace a diseased aortic valve. The potential advantages and disadvantages of these operations will be evaluated in the context of alternative options and relative risks. The different surgical techniques of subcoronary and full root methods will be discussed and important technical aspects reviewed. Long-term outcomes will be described to the extent these are available, including recent publications describing a survival advantage for the Ross. Brief discussions will be presented regarding hemodynamics, child-bearing, endocarditis, and the use of the Ross in pediatric patients as well as biological adaptability of the living pulmonary autograft. PMID- 22041041 TI - Sex and gender in thoracic aortic aneurysms and dissection. AB - Disease of the aorta affects more than 40,000 Americans annually, with a portion of these presentations involving the thoracic aorta. Studies have revealed gender differences in the presentation, management, and outcome of patients with aortic disease. However, most of this work focuses on the abdominal aorta; the data are then extrapolated to the thorax. It is currently established that women with abdominal aortic disease have worse outcomes, are less likely to undergo surgical treatment, and have higher morbidity and mortality. Similar results are seen in the management of women with thoracic aortic dissection. Herein we review the issue of sex and gender differences in thoracic aortic disease. PMID- 22041042 TI - Sex and gender differences in coronary artery disease. AB - Significant sex differences exist between men and women with regard to coronary artery disease. Most notably, this lethal disease kills more women than men each year and remains the leading cause of death for both men and women. Women and men clearly have different risk profiles when diagnosed with coronary artery disease and fare much differently after myocardial infarction and coronary artery bypass grafting. This review summarizes the sex differences in clinical presentation, diagnosis, and the surgical treatment of coronary artery disease between men and women; and potential multifactorial reasons for sex disparities are suggested. PMID- 22041043 TI - The esophagus: do sex and gender matter? AB - The esophagus has a single rudimentary function of active transport of solids and liquids from the pharynx to the stomach and, rarely, venting of the stomach with retrograde passage of gastric contents into the pharynx. It is void of any digestive, absorptive, metabolic, or endocrine functions. Despite this simplicity of function, sex (biological and physiological characteristics, ie, male versus female) and gender (roles, behaviors, activities, and attributes that a given society considers appropriate, ie, man versus woman) differences exist in both normal esophageal function and esophageal disease. Some components of esophageal function are sex-dependent, and these differences must be considered in the interpretation of functional testing. In esophageal disease, particularly gastroesophageal reflux disease, Barrett esophagus, esophageal cancer, acquired immune deficiency syndrome, and scleroderma, there are sex and gender differences in the pathophysiology and response to treatment. Although discussions of treatment and outcomes might differ between the sexes and genders, there are no important data to support different care on the basis of sex or gender. PMID- 22041044 TI - Sex and gender differences in non-small cell lung cancer. AB - Historically, lung cancer has been viewed as a male disease, but during the past 50 years there has been a dramatic increase in the incidence of lung cancer in women. Lung cancer is currently the most common cause of cancer death in American women, accounting for more than one quarter of all cancer deaths. This has been attributed to a significant increase in tobacco consumption by women; however, approximately 1 in 5 women with lung cancer never smoked. As the incidence of lung cancer in women has increased, significant gender-based differences in epidemiology, biology, and treatment responses have become evident and warrant further investigation to advance the treatment of lung cancer in all patients. PMID- 22041045 TI - Aortic valve sparing operations. AB - Aortic valve sparing operations were developed to preserve the aortic valve in patients with ascending aortic aneurysm and aortic insufficiency or patients with aortic root aneurysm. There are 2 types of aortic valve sparing operations, remodeling of the aortic root and reimplantation of the aortic valve. The author believes that remodeling of the aortic root is more appropriate for older patients with ascending aortic aneurysm, dilated aortic sinuses, and normal aortic annulus, whereas reimplantation of the aortic valve is more appropriate for young patients with aortic root aneurysm in whom dilation of the aortic annulus is commonly associated. Although remodeling of the aortic root has been extensively used in patients with aortic root aneurysm, the long-term results are somewhat inferior to reimplantation in most series. The late results of aortic valve sparing operations have been excellent, and these operations have become an important addition to the surgical armamentarium to treat patients with proximal aortic aneurysms. PMID- 22041046 TI - Aortic valve repair for leaflet prolapse. PMID- 22041047 TI - Introduction: esophageal stents for anastomotic leaks and perforations. PMID- 22041048 TI - Esophageal stent placement for the treatment of perforation, fistula, or anastomotic leak. PMID- 22041049 TI - Esophageal stents for leaks and perforations. AB - Stenting of esophageal leaks, ie, anastomotic leaks or perforations, might be a minimally invasive alternative to surgery in most clinical situations. However, it must be emphasized that surgery should be considered if stent treatment in combination with drainage and antibiotics does not improve the clinical condition of the patient. Stent insertion should be performed as soon as possible after diagnosis of the leak. PMID- 22041050 TI - Esophageal stents for leaks and perforations. PMID- 22041051 TI - Introduction: thoracoscopic basilar segmentectomy. PMID- 22041052 TI - Characteristics of the pain observed in the focal vulvodynia syndrome (VVS). AB - Symptoms and signs of patients with focal vulvodynia or vulvo-vestibulitis syndrome (VVS) are variable in location and severity. It is not known whether the location of the most severe pain in the vestibulum is linked to the complaints and perhaps a different entity. A clinical gut feeling suggests that two distinct varieties of focal vulvodynia may be either focused at 2 points (5 and 7 o' clock) or at 4 points (5, 7, 1 and 11 o' clock). A questionnaire was filled out by 30 women with focal vulvodynia during 147 visits and checked for completeness by an independent study nurse. Another investigator to evaluated the clinical signs of VVS, blinded to the patients history or complaints. The visual analogue score (VAS) of pain experienced upon attempt of sexual contact was used as a marker of severity. Focal vulvar pain was assessed using Q-tip with a score from 1 to 10 on 7 areas of the vestibulum. Besides pain during sexual contact, 47% also had pain on inserting a tampon. More than 40% of women suffer since more than 3 years, 70% had to interrupt the act of sexual intercourse mostly or always due to unbearable pain and 25% never had satisfactory sex due to this pain. Feeling deep pain, burning lasting for 12-24h after sexual contact, and stopping the attempt of intercourse were more prominent in women with high pain scores (VAS): 26% of women with VAS>7 had no sex during the last year versus 6% in the group with low pain score (p=0.004). Patients suffering from para-urethral pain zones at 1 and 11 o' clock, have more often pain upon deep penetration, and experienced more pain when inserting tampons than patients with only painful areas at 5 and 7 o' clock (p=0.001). We conclude that patients with severe disease display a different panel of complaints than women with less pain. Patients with focal pain at 1 and 11 o' clock have more deep pain sensations, but feel less pain during insertion of tampons. Hence disease with bi-focal disease may have a different ethiopathogenesis that 4-focal disease. Glands of Bartholin and Skene may be involved in this pathogenenis. PMID- 22041053 TI - Common psychotic symptoms can be explained by the theory of ecological perception. AB - The symptoms of psychiatric illness are diverse, as are the causes of the conditions that cause them. Yet, regardless of the heterogeneity of cause and presentation, a great deal of symptoms can be explained by the failure of a single perceptual function--the reprocessing of ecological perception. It is a central tenet of the ecological theory of perception that we perceive opportunities to act. It has also been found that perception automatically causes actions and thoughts to occur unless this primary action pathway is inhibited. Inhibition allows perceptions to be reprocessed into more appropriate alternative actions and thoughts. Reprocessing of this kind takes place over the entire frontal lobe and it renders action optional. Choice about what action to take (if any) is the basis for the feeling of autonomy and ultimately for the sense-of self. When thoughts and actions occur automatically (without choice) they appear to originate outside of the self, thereby providing prima facie evidence for some of the bizarre delusions that define schizophrenia such as delusional misidentification, delusions of control and Cotard's delusion. Automatic actions and thoughts are triggered by residual stimulation whenever reprocessing is insufficient to balance automatic excitatory cues (for whatever reason). These may not be noticed if they are neutral and therefore unimportant or where actions and thoughts have a positive bias and are desirable. Responses to negative stimulus, on the other hand, are always unwelcome, because the actions that are triggered will carry the negative bias. Automatic thoughts may include spontaneous positive feelings of love and joy, but automatic negative thoughts and visualisations are experienced as hallucinations. Not only do these feel like they emerge from elsewhere but they carry a negative bias (they are most commonly critical, rude and are irrationally paranoid). Automatic positive actions may include laughter and smiling and these are welcome. Automatic behaviours that carry a negative bias, however, are unwelcome and like hallucinations, occur without a sense of choice. These include crying, stereotypies, perseveration, ataxia, utilization and imitation behaviours and catatonia. PMID- 22041054 TI - Complete mitochondrial genome sequences of three bats species and whole genome mitochondrial analyses reveal patterns of codon bias and lend support to a basal split in Chiroptera. AB - Order Chiroptera is a unique group of mammals whose members have attained self powered flight as their main mode of locomotion. Much speculation persists regarding bat evolution; however, lack of sufficient molecular data hampers evolutionary and conservation studies. Of ~1200 species, complete mitochondrial genome sequences are available for only eleven. Additional sequences should be generated if we are to resolve many questions concerning these fascinating mammals. Herein, we describe the complete mitochondrial genomes of three bats: Corynorhinus rafinesquii, Lasiurus borealis and Artibeus lituratus. We also compare the currently available mitochondrial genomes and analyze codon usage in Chiroptera. C. rafinesquii, L. borealis and A. lituratus mitochondrial genomes are 16438 bp, 17048 bp and 16709 bp, respectively. Genome organization and gene arrangements are similar to other bats. Phylogenetic analyses using complete mitochondrial genome sequences support previously established phylogenetic relationships and suggest utility in future studies focusing on the evolutionary aspects of these species. Comprehensive analyses of available bat mitochondrial genomes reveal distinct nucleotide patterns and synonymous codon preferences corresponding to different chiropteran families. These patterns suggest that mutational and selection forces are acting to different extents within Chiroptera and shape their mitochondrial genomes. PMID- 22041055 TI - Cytotoxic and apoptotic effects of six herbal plants against the human hepatocarcinoma (HepG2) cell line. AB - BACKGROUND: Six plants from Thailand were evaluated for their cytotoxicity and apoptosis induction in human hepatocarcinoma (HepG2) as compared to normal African green monkey kidney epithelial cell lines. METHODS: Ethanol-water crude extracts of the six plants were tested with neutral red assay for their cytotoxicity after 24 hours of exposure to the cells. Apoptotic induction was tested in the HepG2 cells with diamidino-2-phenylindole staining. DNA fragmentation, indicative of apoptosis, was analyzed with agarose gel electrophoresis. Alkylation, indicative of DNA damage, was also evaluated in vitro by 4-(4'-nitrobenzyl) pyridine assay. RESULTS: The extract of Pinus kesiya showed the highest selectivity (selectivity index = 9.6) and potent cytotoxicity in the HepG2 cell line, with an IC50 value of 52.0 +/- 5.8 MUg/ml (mean +/- standard deviation). Extract of Catimbium speciosum exerted cytotoxicity with an IC50 value of 55.7 +/- 8.1 MUg/ml. Crude extracts from Glochidion daltonii, Cladogynos orientalis, Acorus tatarinowii and Amomum villosum exhibited cytotoxicity with IC50 values ranging 100-500 MUg/ml. All crude extracts showed different alkylating abilities in vitro. Extracts of P. kesiya, C. speciosum and C. orientalis caused nuclei morphological changes and DNA laddering. CONCLUSION: The extracts of C. speciosum, C. orientalis and P. kesiya induced apoptosis. Among the three plants, P. kesiya possessed the most robust anticancer activity, with specific selectivity against HepG2 cells. PMID- 22041056 TI - Polymersome surface decoration by an EGFP fusion protein employing Cecropin A as peptide "anchor". AB - Polymer based nanocompartments have potential applications in synthetic biology, medicine (drug release) and industrial biotechnology (chiral nanoreactors, multistep syntheses, selective product recovery). A step towards the aforementioned goals is the polymer membrane functionalization through covalent bonding of chemical anchors or insertion of proteins/peptides, to obtain specific properties like recognition, catalytic activity and facilitated diffusion, mimicking the complexity of a biological membrane. The use of genetic engineering techniques widens the possible applications of peptides and proteins specifically designed for polymer membrane interactions. A fusion protein (CecEGFP) based on the antibacterial peptide Cecropin A and the EGFP (Enhanced Green Fluorescent Protein) was designed, expressed and biophysically characterized. CecEGFP interaction with the tri-block copolymer PIB-PEG-PIB (PIB=polyisobutylene, PEG=polyethylene glycol) based polymersome membrane was analyzed by circular dichroism as well as EGFP and Trp fluorescence measurements. Results proved that Cecropin A is usable as a "membrane surface anchor" for water soluble proteins, as it inserts into the polymer membrane. The aim and novelty of this study is within the design of fusion proteins specifically developed for polymer membrane interactions. The use of amphiphilic Cecropin A "anchoring" water soluble proteins to the polymersome surface, avoids chemical coupling between polymers and proteins. PMID- 22041057 TI - Pyrrolamide DNA gyrase inhibitors: optimization of antibacterial activity and efficacy. AB - The pyrrolamides are a new class of antibacterial agents targeting DNA gyrase, an essential enzyme across bacterial species and inhibition results in the disruption of DNA synthesis and subsequently, cell death. The optimization of biochemical activity and other drug-like properties through substitutions to the pyrrole, piperidine, and heterocycle portions of the molecule resulted in pyrrolamides with improved cellular activity and in vivo efficacy. PMID- 22041058 TI - Arylsulfonamidopiperidone derivatives as a novel class of factor Xa inhibitors. AB - The design, synthesis and SAR of a novel class of valerolactam-based arylsulfonamides as potent and selective FXa inhibitors is reported. The arylsulfonamide-valerolactam scaffold was derived based on the proposed bioisosterism to the arylcyanoguanidine-caprolactam core in known FXa inhibitors. The SAR study led to compound 46 as the most potent FXa inhibitor in this series, with an IC(50) of 7 nM and EC(2*PT) of 1.7 MUM. The X-ray structure of compound 40 bound to FXa shows that the sulfonamide-valerolactam scaffold anchors the aryl group in the S1 and the novel acylcytisine pharmacophore in the S4 pockets. PMID- 22041059 TI - Synthesis and growth regulatory activity of a prototype member of a new family of aminothiol radioprotectors. AB - The synthesis, growth inhibition and radioprotective activity of the PrC-210 aminothiol, 3-(methylamino)-2-((methylamino)methyl)propane-1-thiol, and its polyamine and thiolated polyamine progenitors are reported. All of the molecules significantly inhibited growth of cultured normal human fibroblasts. The combination of an ROS-scavenging thiol group and a positively charged alkyl-amine backbone provided the most radioprotective aminothiol molecule. PMID- 22041060 TI - 2,7-Pyrrolo[2,1-f][1,2,4]triazines as JAK2 inhibitors: modification of target structure to minimize reactive metabolite formation. AB - The JAK2/STAT pathway has important roles in hematopoiesis. With the discovery of the JAK2 V617F mutation and its presence in many patients with myeloproliferative neoplasms, research in the JAK2 inhibitor arena has dramatically increased. We report a novel series of potent JAK2 inhibitors containing a 2,7-pyrrolotriazine core. To minimize potential drug-induced toxicity, targets were analyzed for the ability to form a glutathione adduct. Glutathione adduct formation was decreased by modification of the aniline substituent at C2. PMID- 22041061 TI - Synthesis of locked pyranosyl nucleic acid (LpNA). AB - A new locked pyranosyl nucleoside was synthesized by phenylsulfinyl-assisted chemistry. The novel building block was inserted into oligonucleotides and provides new insight on conformational restricted pyranosyl nucleosides on duplex formation. PMID- 22041062 TI - Synthetase polyspecificity as a tool to modulate protein function. AB - The site-specific incorporation of unnatural amino acids (UAAs) into proteins in bacteria is made possible by the evolution of aminoacyl-tRNA synthetases that selectively recognize and aminoacylate the amino acid of interest. Recently we have discovered that some of the previously evolved aaRSs display a degree of polyspecificity and are capable of recognizing multiple UAAs. Herein we report the polyspecificity of an aaRS evolved to encode a comarin containing amino acid. This polyspecificity was then exploited to introduce several UAAs into the fluorophore of GFP, altering its photophysical properties. PMID- 22041063 TI - Carbamates of 4'-demethyl-4-deoxypodophyllotoxin: synthesis, cytotoxicity and cell cycle effects. AB - In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4'-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4' demethyl- 4-deoxypodophyllic)-alpha-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4'-demethyl-4 deoxypodophyllic)-d-alpha-methine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells. PMID- 22041064 TI - Butamben derivatives enhance BMP-2-stimulated commitment of C2C12 cells into osteoblasts with induction of voltage-gated potassium channel expression. AB - As the primary step for 'drug repositioning', we evaluated the effect of 2000 drugs and drug candidates on the commitment of bi-potential mesenchymal precursor C2C12 cells into osteoblasts in the presence of bone morphogenetic protein (BMP) 2 and found that butamben enhanced BMP-2-stimulated induction of alkaline phosphatase, a biomarker of osteoblastogenesis. Investigating the underlying mechanism of its anabolic actions, we found anabolic action of its derivative (compound 4) relies on BMP-2 signaling and mRNA induction of BMPs and voltage gated potassium channels. PMID- 22041065 TI - Flavonol glycosides from Epimedium pubescens. AB - Five new flavonol glycosides (1, 3, 5-7) were isolated from the aerial parts of Epimedium pubescens Maxim., along with two known compounds, sagittasine C (2) and 4',5-dihydroxyl-8-(3,3-dimethylallyl)-flavonol 3-O-[beta-D-xylopyranosyl(1->3)-4 O-acetyl-alpha-L-rhamnopyranoside]-7-O-beta-D-glucopyranoside (4). The structures were elucidated on the basis of their 1D-, 2D-NMR, MS, UV and IR spectra data. PMID- 22041066 TI - Simultaneous determination of ten flavonoids from Viscum coloratum grown on different host species and different sources by LC-MS. AB - A high-performance liquid chromatographic-mass spectrometric method was developed for the simultaneous determination of 10 flavonoids in Viscum coloratum obtained from different host species and different sources. Viscum coloratum was extracted with 50% methanol. The extracts were separated on a C(18) column with a gradient of 0.1% (v/v) formic acid and methanol. The flavonoids in the extracts were detected by negative electrospray ionization mass spectrometry in selective ion monitoring mode. The calibration curves showed good linearity (r>0.998) within the test ranges (homoeriodictyol: 0.149-8.940 ug/ml, homoeriodictyol-7-O-beta-D glycoside: 0.230-13.80 ug/ml, homoeriodictyol-7-O-beta-D-apiose (1->2)-beta-D glycoside: 5.000-300.0 ug/ml, homoeriodictyol-7-O-beta-D-apiose (1->5)-beta-D apiose (1->2)-beta-D-glycoside: 0.835-125.3 ug/ml, rhamnazin-3-O-beta-D glucoside: 0.064-3.840 ug/ml, rhamnazin-3-O-beta-D-(6"-beta-hydroxy-beta methyglutaryl)-glucoside: 1.435-86.10 ug/ml, isorhamnetin-3-O-beta-D-glucoside: 0.930-55.80 ug/ml, 5-hydroxy-3,7,3'-trimethoxyflavone-4'-O-beta-D-glucoside: 0.067-4.020 ug/ml, 5,7,4'-trihydroxy-3,3'-dimethoxyflavone: 0.270-16.20 ug/ml, pachypodol: 0.110-6.600 ug/ml). The limits of quantification were between 0.006 0.720 ug/ml. The assay was reproducible and the overall intra- and inter-day variations were less than 4.6%. The recoveries varied from 93.4 to 103.9% at three different concentration levels. The validation method was used to determine the contents of 10 flavonoids in Viscum coloratum. A one-way analysis of variance was applied to evaluate Viscum coloratum-host-source interactions. Compared with the host species, the sample source had a significant impact on the sample content. PMID- 22041067 TI - Oleanene glycosides of the aerial parts and seeds of Bupleurum falcatum and the aerial parts of Bupleurum rotundifolium, and their evaluation as anti-hepatitis agents. AB - To facilitate effective resource utilization, we have investigated triterpene saponins such as saikosaponin from the aerial parts of Bupleurum (B.) falcatum L., which are commonly discarded. Seven oleanene saponins were isolated from this plant; they were classified as the 13,28-epoxy type, 12-ene type, 9(11),12-diene type, and 28-acid type on the basis of their structural characteristics. For comparison, we also examined the oleanene saponins of the seeds of B. falcatum and the aerial parts of B. rotundifolium L. to obtain seven saponins and one sapogenol from the former and thirteen oleanene saponins from the latter. Several compounds obtained from them were investigated for their hepatoprotective activity and hepatotoxicity. The 13,28-epoxy type saponins had hepatoprotectivity. Ursane type showed hepatotoxicity from middle concentration. The 11,13(18)-diene type saponins did not express hepatoprotective activity. The 28-acid type saponin which has a glucosyl carboxy group showed hepatoprotective action. PMID- 22041068 TI - Garlicnin A from the fraction regulating macrophage activation of Allium sativum. AB - Garlicnin A (1), a new stable, sulfur-containing compound isolated from a fraction of the acetone extracts of Allium sativum L. garlic bulbs, showed the potential to suppress tumor cell proliferation by inhibiting the polarization of M2 alternatively activated macrophages, and its structure was characterized as 3,4-dimethyl-5-(4,5-dithia-1E,7-octadiene)-tetrahydrothiophene-2-sulfoxide-S oxide, on the basis of the results of spectroscopic analysis results. PMID- 22041069 TI - Neolignans from Schisandra wilsoniana and their anti-human immunodeficiency virus 1 activities. AB - Four new neolignans, marphenols G-J (1-4), together with two known ones, were isolated from the leaves and stems of Schisandra wilsoniana. The structures of 1 4 were elucidated by spectroscopic methods, including extensive 1D- and 2D-NMR techniques. New compounds 1-4 were tested for their anti-human immunodeficiency virus (HIV)-1 activities and they showed weak bioactivities. PMID- 22041070 TI - Three new nortriterpene glycosides and two new triterpene glycosides from the bulbs of Scilla scilloides. AB - Three new norlanostane-type triterpene glycosides, scillanostasides A, B, and C, and two new lanostane-type triterpene glycosides, scillanostasides D and E, were isolated from the bulbs of Scilla scilloides Druce (Liliaceae) along with one known norlanostane-type triterpene heptaglycoside, scillascilloside G-1. Their chemical structures were determined on the basis of spectroscopic data as well as chemical evidence. PMID- 22041071 TI - Photochemical cleavage reaction of 8-quinolinyl sulfonates that are halogenated and nitrated at the 7-position. AB - Photochemical bond-cleavage reactions are potentially useful in chemistry, bioorganic chemistry and medicinal chemistry. We previously reported on a photochemical cleavage reaction of 8-quinolinyl sulfonate (8-QS) derivatives in aqueous solution at neutral pH, which we proposed to proceed via an excited triplet state. In this report, we report on the synthesis of some new photocleavable 8-QS derivatives, in which halogen atoms or a nitro group was introduced at the 7-position, in an attempt to improve photoreactive properties and to produce a red-shift in the irradiation wavelength. The introduction of bromine and iodine resulted in an acceleration in the photoreaction by about 1.5 times, possibly due to a heavy atom effect. It was also found that 7-nitro-8-QS absorbs at >360 nm, and, as a result, the S-O bond of this compound can be cleaved by photoirradiation with a fluorescent lamp in aqueous solution and on silicon surface. PMID- 22041072 TI - Androgen receptor antagonists and anti-prostate cancer activities of some synthesized steroidal candidates. AB - In continuation of our previous work, a novel series of steroid derivatives were synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic properties were evaluated. Twenty-one heterocyclic derivatives containing a cyanopyrane ring fused to a steroidal moiety were conveniently synthesized and screened for their antagonistic, antiandrogen and prostate anticancer activities comparable to that of bicalutamide as the reference control. Some of the compounds exhibited better antagonistic, antiandrogen and prostate anticancer activities than the reference controls. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). Synthetic steroidal structures fused to a substituted cyanopyrane ring seem to be a promising approach in the search for novel leads for potent antagonistic, antiandrogen and prostate anticancer agents. PMID- 22041073 TI - Discovery of a novel acyl-CoA: cholesterol acyltransferase inhibitor: the synthesis, biological evaluation, and reduced adrenal toxicity of (4 phenylcoumarin)acetanilide derivatives with a carboxylic acid moiety. AB - As a part of our research for novel potent and orally available acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors that can be used as anti atherosclerotic agents, we recently reported the discovery of the (4 phenylcoumarine)acetanilide derivative 1. However, compound 1 showed adrenal toxicity in animal models. In order to search for safer ACAT inhibitors that do not have adrenal toxicity, we examined the inhibitory activity of ACAT in human macrophage and adrenal cells. The introduction of a carboxylic acid moiety on the pendant phenyl ring and the adjustment of the lipophilicity led to the discovery of (2E)-3-[7-chloro-3-[2-[[4-fluoro-2-(trifluoromethyl)phenyl]amino]-2-oxoethyl] 6-methyl-2-oxo-2H-chromen-4-yl]phenyl]acrylic acid (21e), which showed potent ACAT inhibitory activity in macrophages and a selectivity of around 30-fold over adrenal cells. In addition, compound 21e showed high adrenal safety in guinea pigs. PMID- 22041074 TI - Synthesis and pharmacological evaluation of 1-alkyl-N-[(1R)-1-(4-fluorophenyl)-2 methylpropyl]piperidine-4-carboxamide derivatives as novel antihypertensive agents. AB - We synthesized and evaluated inhibitory activity against T-type Ca(2+) channels for a series of 1-alkyl-N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]piperidine-4 carboxamide derivatives. Structure-activity relationship studies have revealed that the isopropyl substituent at the benzylic position plays an important role in exerting potent inhibitory activity, and the absolute configuration of the benzylic position was found to be opposite that of mibefradil, which was first launched as a new class of T-type Ca(2+) channel blocker. Oral administration of N-[(1R)-1-(4-fluorophenyl)-2-methylpropyl]-1-[2-(3-methoxyphenyl)ethyl]piperidine 4-carboxamide (17f) lowered blood pressure in spontaneously hypertensive rats without inducing reflex tachycardia, an adverse effect often caused by traditional L-type Ca(2+) channel blockers. PMID- 22041075 TI - Antitumor effect of liposomal histone deacetylase inhibitor-lipid conjugates in vitro. AB - Histone deacetylase inhibitor (HDACI), suberoylanilide hydroxamic acid (SAHA), approved by the Food and Drug Administration (FDA) for the treatment of cutaneous T cell lymphoma, is a promising new treatment strategy for various cancers. In this study, we hypothesized that a liposomal formulation of HDACI might efficiently deliver HDACI into tumors. To incorporate HDACI efficiently into the liposomal membrane, we synthesized six HDACI-lipid conjugates, in which polyethylene glycol(2000) (PEG(2000))-lipid or cholesterol (Chol) was linked with a potent hydroxamic acid, HDACI, SAHA or K-182, by cleavable linkers, such as ester, carbamide and disulfide bonds. Liposomal HDACI-lipid conjugates were prepared with distearoylphosphatidylcholine (DSPC) and HDACI-Chol conjugate or with DSPC, Chol and HDACI-PEG-lipid conjugates, and their cytotoxicities were evaluated for human cervix tumor HeLa and mouse colon tumor Colon 26 cells. Among the liposomes, liposomal oleyl-PEG(2000)-SAHA conjugated with SAHA and oleyl PEG(2000) via a carbamate linker showed higher cytotoxicity via hyperacetylation of histone H3 and induction of caspase 3/7 activity. These results suggested that liposomal HDACI-lipid conjugates may be a potential tool for cancer therapy. PMID- 22041076 TI - Two new flavone C-glycosides from Trollius ledebourii. AB - Two new flavone C-glycosides, trollisin A (1) and trollisin B (2), along with seven known flavonoids, isoswertisin (3), isoswertiajaponin (4), orientin (5), 2" O-beta-L-galactopyranosylvitexin (6), 2"-O-beta-L-galactopyranosylorientin (7), neodiosmin (8) and acacetin-7-O-neohesperidoside (9) were isolated from the flowers of Trollius ledebourii REICHB. The structures of the new compounds were elucidated based on spectral analysis, including MS, 1D- and 2D-NMR experimentation. PMID- 22041077 TI - Chemical constituents from Sambucus adnata and their protein-tyrosine phosphatase 1B inhibitory activities. AB - The MeOH extract from the whole plants of Sambucus adnata has shown significant protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity. Chemical study on the extract resulted in the isolation of thirteen compounds, including a novel triterpene (1). The structure of 1 was determined to be 1alpha,3beta-dihydroxy urs-12-en-11-one-3-yl palmitate on the basis of extensive spectroscopic analyses. Among the isolated compounds, ursolic acid, oleanolic acid and (+/-)-boehmenan showed the most potent PTP1B inhibitory activity in vitro with the IC(50) values of 4.1, 14.4 and 43.5 um, respectively. The kinetic analysis indicated that (+/-) boehmenan inhibits PTP1B activity in a competitive manner. PMID- 22041078 TI - Adsorption of cadmium ions by wheat bran treated with pectinase. AB - In this study, we investigated the surface properties of raw wheat bran (R-WB) and wheat bran treated with Pectinase PL (P-WB) to evaluating its efficacy for removal of cadmium from waste water. The concentration of cadmium ions adsorbed by them was evaluated. The concentration of carboxyl groups of R-WB (3.56 mmol/g) was greater than that of P-WB (2.11 mmol/g), which indicated that the pectin of R WB was broken down, resulting in a decrease in the concentration of carboxyl groups due to the enzyme treatment. From the scanning electron microscope (SEM) images of P-WB, the pores were newly generated with enzyme treatment. The concentration of cadmium ions adsorbed onto R-WB was greater than that of cadmium ions adsorbed onto P-WB. These results show that the adsorption mechanism of cadmium ions onto R-WB and P-WB depends on the carboxyl groups of pectin. PMID- 22041079 TI - New solanocapsine-type tomato glycoside from ripe fruit of Solanum lycopersicum. AB - A new solanocapsine-type tomato glycoside, a novel and interesting natural steroidal glycoside, was isolated from a mini tomato, Solanum lycopersicum L. The chemical structure of the new minor glycoside, esculeoside B-5 (3), was determined to be (5S,22R,23S,24R,25S)-22,26-epimino-16beta,23-epoxy-3beta,23,24 trihydroxycholestane 3-O-beta-lycotetraoside. PMID- 22041080 TI - Efficient improved extraction of tomato saponin using shock waves. AB - In the conventional method of mixer blending extraction, the yields of the tomato saponin, esculeoside A, in the mini and middy tomatoes were found to be 0.043% and 0.046%, respectively. In order to improve the yields, we attempted a more efficient extraction using shock waves. The yields of esculeoside A were 0.0987% in air after 1 shock, 0.0792% in air after two shots, 0.0648% in half water after 1 or 2 shocks, and 0.0599% in water after 1 or 2 shocks. The yields obtained by the proposed method were approximately twice those of the conventional mixer blending method; therefore, this method is regarded to be very efficient. Moreover, two spirosolane glycosides, tomatine and lycoperoside A, were obtained for the first time from the ripe tomato fruit in this method. To date, these compounds have not been obtained with the mixer blending method. However, whether these glycosides are produced from esculeoside A or are newly extracted from the plant organ by the shock wave is still unclear. PMID- 22041081 TI - New cannabinoid-like chromane and chromene derivatives from Rhododendron anthopogonoides. AB - Two new cannabinoid-like chromane and chromene derivatives named anthopogocyclolic acid (1) and anthopogochromenic acid (2) and five related compounds (3-7) which are known as synthetic analogues of cannabinoids: cannabichromene (CBC) type, cannabicyclol (CBL) type, and cannabicitran (CBT) type, have been isolated together with geranyl orsellinic acid (8) from the Chinese medicinal plant Rhododendron anthopogonoides. Their structures were elucidated based on spectroscopic and chemical evidence. The absolute configuration of the asymmetric carbons at C-2 of 1-7 was determined to be S from their circular dichroism (CD) spectra. Compounds 2, 4 and 6 inhibited compound 48/80-induced histamine release from rat peritoneal mast cells. PMID- 22041082 TI - Cytotoxicity of new 5-phenyl-4,5-dihydro-1,3,4-thiadiazole analogues. AB - A series of 5-phenyl-4,5-dihydro-1,3,4-thiadiazoles were synthesized and their cytotoxicity was examined against four human cancer cell lines, e.g. lung cancer (A549), ovarian cancer (SK-OV-3), skin cancer (SK-MEL-2), and colon cancer (HCT15). The title compounds were synthesized by condensation of thiosemicarbazide with substituted benzaldehydes, followed by cyclization with acetic anhydrides in good yields. Most of the compounds exhibited significant suppressive activity against the growth of all of the cancer cell lines. The 4 hydroxy analogue of 5-phenyl-4,5-dihydro-1,3,4-thiadiazole (2h) was most active in the inhibition of growth of the SK-MEL-2 cell line, with an IC(50) value of 4.27 ug/ml; followed by compound 2a (IC(50) 5.16 ug/ml). The compounds 2j, 2h, and 2b, bearing 3-methoxy-4-hydroxy-, 4-hydroxy- and 4-methyl substituents in the C-5 phenyl ring respectively, exhibited the highest activity against the SK-OV-3 (IC(50) 7.35 ug/ml), HCT15 (IC(50) 8.25 ug/ml) and A549 (IC(50) 9.40 ug/ml) cell lines, respectively. A structure-activity relationship study revealed that an optimal electron density on the C-5 phenyl ring of 1,3,4-thiadiazoles is crucial for their cytotoxic activity against the human cancer cell lines used in the present study. PMID- 22041083 TI - Oleanolic triterpene saponins from the roots of Panax bipinnatifidus. AB - Ten oleanane-type saponins (1-10), including three new compounds, namely bifinosides A-C (1-3), were isolated from the roots of Panax bipinnatifidus SEEM. Their structures were elucidated on the basis of chemical and spectroscopic methods. PMID- 22041084 TI - Secolignans, neolignans and phenylpropanoids from Daphne feddei and their biological activities. AB - Two new secolignans and one new neolignan, named feddeiphenols A-C (1-3), together with eight known compounds (4-11), were isolated from the leaves and stems of Daphne feddei. Their structures were established on the base of spectroscopic methods, mainly extensive NMR, UV spectroscopy, and MS spectrometry. Compounds 1-11 were tested for their anti-human immunodeficiency virus (HIV)-1 activity and cytotoxicity. The results revealed that compounds 1, 2, 3, 7, and 9 showed therapeutic index (TI) values above 30, respectively, and the other compounds also showed weak anti-HIV-1 activity. Compound 1 showed modest cytotoxic activity. The other compounds also showed weak cytotoxic activity. PMID- 22041085 TI - Bioactive phenolic constituents from the seeds of Pharbitis nil. AB - Two new lignans, termed pharsyringaresinol (1) and pharbilignoside (2), a new phenylethanoid glycoside, termed pharbiniloside (3), and 22 known compounds, were isolated from the ethanol extract of the seeds of Pharbitis nil. The structures of the new compounds (1-3) were determined on the basis of spectroscopic analyses, including 2D-NMR and circular dichroism (CD) spectroscopy studies. Among the isolates, compounds 2, 11, 12, and 24 exhibited significant cytotoxicity against human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) with IC(50) values ranging from 8.07 to 28.30 uM. In addition, compounds 11, 12 and 24 potently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, a microglia cells with IC(50) values ranging from 14.7 to 19.9 uM. PMID- 22041086 TI - Sesquiterpenes from the secondary metabolites of Streptomyces sp. (YIM 56130). AB - Three new sesquiterpenes were isolated from the fermentation broth of Streptomyces sp. and their structures were determined as caryolane-1,7alpha-diol (1), 1,6,11-eudesmanetriol; (1alpha,6beta)-form (2), 11-eudesmene-1,6-diol; (1alpha,6beta)-form (3), together with nine known compounds as caryolane-1,9alpha diol (4), 2-methyl-5-nonanol (5), soyasaponin I (6), cyclo (Ala-Leu) (7), homononatinic acid (8), beta-sitosteryl glucoside-3'-O-heptadecoicate (9), 2' deoxythymidine (10), 2'-deoxyuridine (11), trehalose (12). The structures were elucidated by spectral analysis. PMID- 22041087 TI - Ethnicity differences in child and parental outcomes following involvement the PACE program. AB - This study investigated ethnic differences in the extent to which engagement (i.e., attendance and quality of participation) in the PACE (Parenting our Children to Excellence) program predicted positive child and parent outcomes. PACE is an 8-week preventive intervention aimed at parents of preschool children. The study investigated the relation of engagement to outcomes in an ethnically diverse sample of 298 African American and 280 European American parents. Overall results demonstrated that engagement in PACE significantly improved child and parent outcomes for both African American and European American participants. Some improvements were evident at post-assessment already and were maintained or became stronger at a one-year follow-up assessment, whereas others only became evident at follow-up. Specifically, results revealed that attendance in PACE significantly improved child coping competence and parenting stress for both the African American and European American samples. PACE attendance also significantly improved child behavior problems, parental satisfaction and parental efficacy for the European American sample. Findings indicate that PACE is a promising intervention for parents of African American and Caucasian preschoolers; although further research and program refinement is necessary in order to understand the mechanisms with the PACE intervention that seem to vary for African American compared to Caucasian families. PMID- 22041088 TI - Determination of the new anthelmintic monepantel and its sulfone metabolite in milk and muscle using a UHPLC-MS/MS and QuEChERS method. AB - This is the first paper to report a method for the detection of the new anthelmintic monepantel and its sulfone metabolite in goat's milk and ovine muscle. Samples were extracted and purified using a modified QuEChERS method. A concentration step was included when analyzing in the low MUg kg(-1) range. Analysis was carried out by ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in a 13min run time using atmospheric pressure electrospray ionisation in the negative mode (ESI(-)) and multiple reaction monitoring (MRM) scanning. Monepantel (m/z 472) and monepantel-sulfone (m/z 504) both had product ions at m/z 186 and m/z 166. The method has been single laboratory validated according to the 2002/657/EC guidelines. The mean recovery in milk was 108 and 106% for monepantel and monepantel-sulfone, respectively. The mean recovery in muscle was 109 and 108% for monepantel and monepantel-sulfone, respectively. The coefficients of variation for the within laboratory repeatability and reproducibility were <=6.4% in milk and <=14.2% in muscle. The decision limits (CCalpha) in milk were 2.20 and 2.08 MUg kg(-1) for monepantel and monepantel-sulfone, respectively. The decision limits (CCalpha) in muscle were 771 and 746 MUg kg(-1) for monepantel and monepantel-sulfone, respectively. PMID- 22041089 TI - Direct analysis of carbohydrates in animal plasma by ion chromatography coupled with mass spectrometry and pulsed amperometric detection for use as a non invasive diagnostic tool. AB - The present paper demonstrates that electrochemical detection (ECD) coupled to ion chromatography and electrospray ionization tandem mass spectrometry (IC-ECD ESI/MS/MS) can be used to rapidly estimate some indications of the health status of organisms. The lactulose to mannitol ratio (L/M) is used as a non-invasive assay to investigate small intestinal absorption pathways and mucosal integrity. In the present study, an evaluation of the negative effects of nonsteroidal anti inflammatory drug meloxicam perorally administrated to a group of dogs was carried out by determining the lactulose/mannitol index using the IC-ECD ESI/MS/MS hyphenated technique. According to the results of the study, meloxicam altered gastrointestinal permeability. Coenzyme Q(10) (CoQ(10)) was tested to determine if it could prevent meloxicam induced gastrointestinal damage and it was found that CoQ(10) could be an effective preventive treatment. Furthermore, plasma glucose concentration level was determined to be an indirect indicator of the oxidative state in the blood. To find out the beneficial effects of a double antioxidant combination (alpha-lipoic acid (ALA) and CoQ(10)) on the total glucose level in chickens, ALA and CoQ(10) were provided as food additives in factory farm raised chicken. The results of the pilot study indicate that the glucose level in the plasma of chickens group fed with CoQ(10) and ALA was significantly decreased compared to the control group. Ion chromatography (IC) utilizing pulsed amperometric detection (PAD) was compared to ion chromatography coupled with tandem mass spectrometry (MS/MS) as an analytical tool for monitoring the carbohydrate level in biological fluids. In electrochemical detection, the newly developed two-pulse waveform successfully withstands matrix effects in biological samples. Continuous on-line desalting of the high salt concentrations used as the eluent for carbohydrate separation from the anion exchange column allows coupling of IC and MS techniques. A make-up solution (0.5mM LiCl) was delivered prior to MS detection for efficient ionization of eluted carbohydrates. Method validation showed that both used techniques are practically comparable and some advantages of each are presented. PMID- 22041090 TI - Quantification of lactose content in human and cow's milk using UPLC-tandem mass spectrometry. AB - A sensitive, accurate, and specific quantitative UPLC-MS/MS method was developed for lactose measurement of cow's and human milk and validated with cow's milk samples certified by an external laboratory. The new method employs only a dilution of raw cow's and human milk for simple preparation with no need to remove protein and fat prior to analysis with UPLC-MS/MS. It was operated in negative mode to detect lactose molecules and labeled (13)C(12)-lactose with the highest sensitivity. The principle advantages of the new LC-MS/MS method were: completed lactose determination in 5 min, absolute recovery of 97-107%, lower limit of detection <5 ng/L, and 99% linearity over the concentration range of 0.7 4.4 mg/L for both cow's and human milk. The mean lactose concentration of 51 human milk samples was measured as 56.8 +/- 5.5 g/L ranging from 43 to 65 g/L. The described method represents validated lactose analysis with high accuracy and precision for a routine lactose determination in raw human milk. PMID- 22041091 TI - Disappearance of cerebrospinal fluid oligoclonal bands after natalizumab treatment of multiple sclerosis patients. AB - Intrathecal immunoglobulin synthesis in an oligoclonal pattern is the most common immunologic abnormality detected in MS patients. Various treatments, such as immunomodulators and immunosuppressors, have not been found to modify it. Natalizumab hinders migration of encephalitogenic T-cells into the central nervous system (CNS), reducing inflammatory response. Its impact on CSF oligoclonal bands (OCBs) has not been demonstrated. This report describes its effect in four out of six patients with multiple sclerosis after a mean of 10 infusions: the CSF was negative for OCBs at the second lumbar puncture. In conclusion, natalizumab treatment can reduce CSF OCBs to undetectable levels, although the clinical significance of this observation is not yet known. PMID- 22041092 TI - Month of birth is associated with multiple sclerosis but not with HLA-DR15 in Finland. AB - BACKGROUND: Spring birth has been found to be associated with increase in the risk of MS. However, this effect is reportedly found particularly in HLA-DR15 positive patients. OBJECTIVE: Examine the month of birth (MOB) effect in Finnish MS patients and its association with HLA-DR15. METHODS: Using the national register on hospitalizations during 1979-2004 we identified 8359 MS patients. We used a chi(2)-analysis to compare the distribution of MOB in MS patients versus age-adjusted controls. Patients were subdivided into 10-year birth cohorts to analyse temporal variations in MOB. A subgroup of HLA-typed MS patients (n = 657) and a population sample of healthy donors from the Finnish Bone Marrow Donor Registry (n = 19,805) were included to analyse connections between HLA-DR15 and MOB. RESULTS: An April birth was associated with a 9.4% increased risk of MS (p = 0.008), whereas November birth was associated with an 11.1% decreased risk (p = 0.004) compared with the expected birth distribution. No temporal clustering in the MOB effect was found during 1900-1988. Both HLA-DR15 positive (34% increase, p = 0.043) and DR15 negative (48% increase, p = 0.0095) MS patients exhibited an increase in spring births (in May). HLA-DR15 in healthy subjects was not associated with MOB. CONCLUSIONS: We confirm that spring birth increases MS risk. This phenomenon was not associated with HLA-DR15 and there was no evidence of temporal clustering. The MOB effect suggests that early developmental processes may modulate MS risk. PMID- 22041093 TI - Screening for the risk of job loss in multiple sclerosis (MS): development of an MS-specific Work Instability Scale (MS-WIS). AB - BACKGROUND: Multiple sclerosis (MS) mainly presents amongst those of working age. Depending upon the type of MS, many people embark upon a long period of managing their day-to-day work-related needs in the face of intermittent and sometimes persistent disabling symptoms. The objective of this study was to explore the concept of work instability (WI) following the onset of MS and develop a Work Instability Scale (WIS) specific to this population. METHOD: WI amongst those with MS in work was explored through qualitative interviews which were then used to generate items for a WIS. Rasch analysis was used to refine the scaling properties of the MS-WIS, which was then validated against expert vocational assessment by occupational health physiotherapists and ergonomists. RESULTS: The resulting measure is a 22-item, self-administered scale which can be scored in three bands indicating low, medium and high risk of WI (job retention) problems. The scale meets modern psychometric requirements for measurement, indicated by adequate fit to the Rasch model with absence of local dependency and differential item functioning (DIF) by age, gender and hours worked. CONCLUSIONS: The scale presents an opportunity in routine clinical practice to take positive action to reduce sickness absence and prevent job loss. PMID- 22041094 TI - Mixed effect of tocilizumab in spondylarthritis. Comments about the article by Wendling et al. entitled "Short-term effect of IL-6 inhibition in spondylarthritis". Joint Bone Spine 2010;77:624-5. PMID- 22041095 TI - Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients. AB - BACKGROUND: Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, reduced dose 0.5 mg/kg/m), or switch to agalsidase alpha (administered dose 0.2 mg/kg/eow). An assessment report from the European Medicines Agency (EMA) raised serious concerns about an increase in adverse events at lower dosages of agalsidase beta. We determined the influence of the shortage on clinical event incidence and the most sensitive biochemical marker (lysoGb3) in Dutch Fabry patients. METHODS: The incidence of clinical events per person per year was calculated from start of agalsidase beta treatment until the shortage, and was compared to the incidence of clinical events during the shortage period. In addition, plasma lysoGb3, eGFR, quality of life (SF-36) and brief pain inventory (BPI) questionnaires were analysed. RESULTS: All thirty-five Dutch Fabry patients using agalsidase beta (17 males) were included. Mean clinical event incidence was unchanged: 0.15 events per person per year before versus 0.15 during the shortage (p = 0.68). In total 28 clinical events occurred in 14 patients during 4.6 treatment years, compared to 7 events in 6 patients during the 1.3 year shortage period. eGFR and BPI scores were not significantly altered. Two SF-36 subscales were significantly but minimally reduced in females. In males, lysoGb3 increased with a median of 8.1 nM (range 2.5-29.2) after 1 year of shortage (p = 0.001). Increases in lysoGb3 were found in both patients switching to agalsidase alpha and on a reduced agalsidase beta dose. Antibody status, treatment duration or clinical event incidence showed no clear correlation to lysoGb3 increases. CONCLUSIONS: No increase in clinical event incidence was found in the adult Dutch Fabry cohort during the agalsidase beta shortage. Increases in lysoGb3, however, suggest recurrence of disease activity. PMID- 22041096 TI - Reliability and Minimal Detectible Change values for gait kinematics and kinetics in healthy adults. AB - Computerized assessment of gait is commonly used in both research and clinical settings to quantify gait mechanics and detect change in performance. Minimal Detectable Change values have only recently been reported, are only available for patient populations, and in many cases exceed 10 degrees . Twenty nine healthy individuals underwent two biomechanical gait assessments separated by 5.6 (SD 2.2) days, with two raters for each session. All subjects walked at a self selected pace and three controlled velocities. ICC, SEM and MDC for kinematic and kinetic measures were calculated for interrater-intrasession, intrarater intersession and interrater-intersession. ICC values were in the good to excellent range (r>0.75) for all kinematic and kinetic variables and all comparisons. MDC values were lower than previously published data for all similar comparisons. The results of the current study suggest that reliability is good to excellent across a range of controlled walking velocities and the introduction of a second rater does not appreciably impact ICC or MDC values. In young healthy adults changes in gait kinematics of greater than approximately 5 degrees can be identified when comparing between sessions. PMID- 22041097 TI - Age- and speed-related differences in harmonic ratios during walking. AB - Harmonic ratios (HRs), derived from trunk accelerations, measure smoothness of trunk motion during gait; higher ratios indicate greater smoothness. Previous research indicates that young adults optimize HRs at preferred pace, exhibiting reduced HRs at speeds faster and slower than preferred. Recent studies examining HRs and other trunk acceleration measures challenge this finding. The purpose of this study was to examine age-related differences in HRs across a range of self selected overground walking speeds. Anteroposterior (AP), vertical (VT), and mediolateral (ML) HRs were examined in 13 young adults (ages 20-23), 13 healthy older adults (ages 60-69), and 13 healthy old-old adults (ages 80-86) while walking overground at very slow, slow, preferred, fast, and very fast speeds. Young and older adults exhibited similar HRs in all directions of motion across speeds, while old-old adults exhibited lower AP- and VT-HRs. All groups exhibited reduced HRs at speeds slower than preferred. However, there were no differences in HRs between preferred and faster speeds, with the exception of reduced VT-HRs in the very fast condition for the older groups. The ML-HR was not different between groups, and varied less across speeds. Stride time variability exhibited inverse relations with, and independently contributed to, HRs across speeds; lower stride time variability was associated with greater smoothness of trunk motion. Older groups were not disproportionately affected by walking more slowly and smoothness of trunk motion did not show a clear pattern of optimization at preferred pace for any group. PMID- 22041098 TI - Acute responses of brown mussel (Perna perna) exposed to sub-lethal copper levels: integration of physiological and cellular responses. AB - This study examined the effect of sub-lethal copper levels on selected physiological and cellular responses of the marine bivalve Perna perna. Animals were exposed to five environmentally relevant concentrations of 12.5, 25.0, 37.5 and 50.0 MUg L-1 copper and metal accumulation was found to be significantly increased at the two higher copper concentrations after 24 h of exposure. Physiological responses found to increase during acute copper exposure included mucus secretion rate (at 25 and 50 MUg L-1 copper), nitrogen excretion rates and oxygen consumption rates (both at 25 and 50 MUg L-1 copper). Perna perna changed its substrate utilisation at 25, 37.5 and 50 MUg L-1 copper in favour of protein based metabolism. A higher degree of ROS induced DNA damage was observed at acute exposure to 37.5 and 50 MUg L-1 copper. Filtration rate was unchanged during acute copper exposure. A model is proposed that integrates cellular and physiological responses to copper during short-term acute and long-term chronic exposures. PMID- 22041099 TI - Evolution of pH during immersion of meat protein matrices in acidic marinades. AB - The pH value is a fundamental datum to be monitored during marination. A method is proposed for calculating the evolution of pH of turkey meat cubes during marination in an acetic acid solution. It is based on measurement of the buffering capacity by acidification using a strong acid. A calculation based on the dissociation equilibrium of acetic acid is used to estimate the mean pH reached, factoring in the acid content of the meat. For long marination times, the calculated pH is over-evaluated in relation to the experimental value. This can be explained by the significant loss of buffering substances during immersion. After 6h of immersion, the matrix's proton binding capacity may be reduced to just 20% of the initial value. Hence to improve the prediction of meat cut pH during marination, it is necessary to factor in the outgoing flow of buffering substances. PMID- 22041100 TI - Movable computer ruler (MCR): a new method for measuring the size of Toxoplasma gondii cysts, tachyzoites and other selected parasites. AB - A new method for measuring the size of parasites and other objects using optical microscopy was developed using a specifically designed movable computer ruler (MCR) derived from digital images of a stage micrometer. Subsequently, MCR can be superimposed on images of parasites to measure their size. MCR derived from the stage micrometer under a particular objective lens can be used to measure the size of an object acquired by the same lens/microscope/camera system. The conditions are fixed for every superimposed image including width, height, pixel number and density. The MCR was tested using selected parasites, and shown to be as accurate as the ocular micrometer disk, screw micrometer eyepiece and image analysis software. The lower technical complexity of the MCR method makes it applicable even in laboratories with limited resources. PMID- 22041101 TI - Morphology and distribution of blood fluke eggs and associated pathology in the gills of cultured Pacific bluefin tuna, Thunnus orientalis. AB - Infestations of blood flukes of the genus Cardicola have been observed in juvenile Pacific bluefin tuna (PBT) cultured in Japan. Infected fish harbor large numbers of parasite eggs in their gills. Although the link between blood fluke infection and juvenile mortality is not clear, accumulation of parasite eggs appears to be pathogenic to the fish. We investigated the origins, general morphology/distribution, and histopathology of these eggs in artificially produced 0 yr old PBT. Dead and live fish were sampled on several occasions from two culture facilities in Wakayama prefecture, Japan. The number of eggs in each gill filament was enumerated under a microscope. In addition, we estimated the total number of eggs by dissolving the gills in a weak NaOH solution. We observed two morphologically distinct egg types in the gill filaments, smaller, oval shaped eggs in the gill lamellae and larger, crescent shaped eggs that occurred primarily in the filamentary arteries. Based on the ITS2 sequence, the ovoid and crescent shaped eggs were identified as C. orientalis and C. opisthorchis, respectively. Eggs of the former species were more abundant (maximum: 6400 per filament) than the latter (maximum: 1400), but the number was highly variable among filaments. The eggs of the latter species were relatively evenly distributed among the filaments. In a heavily infected individual, we estimated a total of >4.5 million eggs were present in the gills on one side of the fish. The number of eggs from the two species was positively correlated to each other and the dead fish tended to harbor more eggs than the live fish. Histological observation revealed host responses around the eggs, including encapsulation by fibroblasts and nodule formation, as seen in response to other aporocotylid eggs. In addition, we observed widespread fusion of gill lamellae and blockage of the filamentary arteries in some instances. Our results provide information that can be used for routine diagnosis of Cardicola blood flukes in cultured tuna and suggest they represent a risk to juvenile PBT. PMID- 22041102 TI - Intestinal parasitosis and shigellosis among diarrheal patients in Gondar teaching hospital, northwest Ethiopia. AB - BACKGROUND: Diarrheal diseases are the major causes of morbidity and mortality in developing world. Understanding the etiologic agents of diarrheal diseases and their association with socio-demographic characteristics of patients would help to design better preventive measures. Thus, this study was aimed to determine the prevalence of intestinal parasites and enteropathogenic bacteria in diarrheic patients. METHODS: A cross-sectional study involving 384 consecutive diarrheal patients who visited Gondar teaching hospital, Gondar, Ethiopia from October 2006 to March 2007 was conducted. Stool specimens were collected and examined for intestinal parasites and enteropathogenic bacteria following standard parasitological and microbiological procedures. RESULTS: Intestinal parasites were diagnosed in 36.5% of the patients. The most frequently encountered protozoan parasite was Entamoeba histolytica/dispar (7.3%) followed by Giardia lamblia (5.0%), Cryptosporidium parvum (1.8%) and Isospora belli (1.3%). The dominant helminthic parasite identified was Ascaris lumbricoides (5.5%) followed by Strongyloides stercoralis and Schistosoma mansoni (3.1% each), hookworm infection (1.8%), and Hymenolepis species (1.3%). Multiple infections of intestinal parasites were also observed in 6.3% of the patients. Among the enteropathogenic bacteria Shigella and Salmonella species were isolated from 15.6% and 1.6%, respectively, of the patients. Escherichia coli O57:H7 was not found in any of the stool samples tested. Eighty eight percent and 83.3% of the Shigella and Salmonella isolates were resistant to one or more commonly used antibiotics, respectively.Intestinal parasitosis was higher in patients who live in rural area, in patients who were washing their hands after visiting toilet either irregularly with soap and without soap or not at all, in patients who used well and spring water for household consumption, and in patients who had nausea (P < 0.05). Statistically significant associations were also observed between Shigella infections and patients who were using well and spring water for household consumption, and patients who had dysentery and mucoid stool (P < 0.05). CONCLUSIONS: The high prevalence of intestinal parasites and Shigella species in diarrheic patients calls for institution of appropriate public health intervention measures to reduce morbidity and mortality associated with these diseases. The rational use of antibiotics should also be practiced. PMID- 22041104 TI - Iridoids as chemical markers of false ipecac (Ronabea emetica), a previously confused medicinal plant. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Several roots or rhizomes of rubiaceous species are reportedly used as the emetic and antiamoebic drug ipecac. True ipecac (Carapichea ipecacuanha) is chemically well characterized, in contrast to striated or false ipecac derived from the rhizomes of Ronabea emetica (syn. Psychotria emetica). Besides its previous use as substitute of ipecac, the latter species is applied in traditional medicine of Panama and fruits of its relative Ronabea latifolia are reported as curare additives from Colombia. MATERIALS AND METHODS: Compounds of Ronabea emetica were isolated using standard chromatographic techniques, and structurally characterized by NMR spectroscopy and mass spectrometry. Organ specific distribution in Ronabea emetica as well as in Ronabea latifolia was further assessed by comparative HPLC analysis. RESULTS: Four iridoid-glucosides, asperuloside (1), 6alpha-hydroxygeniposide (2), deacetylasperulosidic acid (3) and asperulosidic acid (4) were extracted from leaves of Ronabea emetica. Rhizomes, used in traditional medicine, were dominated by 3. HPLC profiles of Ronabea latifolia were largely corresponding. These results contrast to the general tendency of producing emetine-type and indole alkaloids in species of Psychotria and closely related genera and merit chemotaxonomic significance, characterizing the newly delimited genus Ronabea. CONCLUSIONS: The aim of the work was to resolve the historic problem of adulteration of ipecac by establishing the chemical profile of Ronabea emetica, the false ipecac, as one of its less known sources. The paper demonstrates that different sources of ipecac can be distinguished by their phytochemistry, thus contributing to identifying adulterations of true ipecac. PMID- 22041103 TI - Inhibitory effects of the root extract of Dipsacus asperoides C.Y. Cheng et al T.M.Ai on collagen-induced arthritis in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Dipsaci radix, the dried root of Dipsacus asperoides C.Y. Cheng et al T.M.Ai is used as a medicinal plant in oriental clinics for the treatment of bone diseases and functions by strengthening bone and healing bone fractures. AIM OF THE STUDY: This study investigated the therapeutic efficacy of Dipsaci radix in treating rheumatoid arthritis using a type II collagen (CII)-induced arthritis (CIA) mouse model. MATERIALS AND METHODS: Arthritis was induced in male DBA/1 mice by immunization with CII. Dipsaci radix water (DR-W) extract at 50mg/kg and 100mg/kg was orally administered from days to after the induction of arthritis. Arthritic score, serum levels of anti-CII IgG2a, the inflammatory mediator prostaglandin E(2) (PGE(2)), and inflammatory cytokines (TNF-alpha, IL-1beta and IL-6), and histological changes in the ankle joint were analyzed in CIA mice. RESULTS: Arthritic induction increased the arthritic score, as well as serum levels of anti-CII IgG2a antibody, PGE(2), TNF-alpha, IL-1beta and IL-6 in mice. However, administration of DR-W extract in CIA mice significantly reduced arthritic scores and serum levels of anti-CII IgG2a antibody, PGE(2), TNF-alpha, IL-1beta and IL-6 compared with those in vehicle-treated CIA mice. Furthermore, histopathological improvement in joint architecture was also observed in DR-W extract-treated CIA mice. CONCLUSIONS: DR-W extract has anti-inflammatory and anti-arthritic effects in arthritic mice. This suggests that Dipsaci radix might be used as a therapeutic agent for the treatment of human arthritis. PMID- 22041105 TI - In vitro chemo-preventative activity of Crotalaria agatiflora subspecies agatiflora Schweinf. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Crotalaria species have been widely used in Chinese traditional medicine to treat several types of internal cancers. Crotalaria agatiflora is used as a medicinal plant in several African countries for the treatment of bacterial and viral infections as well as for cancer. MATERIALS AND METHODS: Water and ethanol extracts of the leaves of Crotalaria agatiflora were evaluated for cytotoxicity on four cancerous and one noncancerous cell lines, using XTT (Sodium 3'-[1-(phenyl amino-carbonyl)-3,4-tetrazolium]-bis [4-methoxy-6-nitro] benzene sulfonic acid hydrate) colorimetric assay. Antioxidant activity was determined using DPPH (1,1-diphenyl-2-picryl hydrazyl). Light microscopy (eosin and haematoxylin staining) and flow cytometry (Annexin-V and propidium iodide) were used to evaluate the mechanism of action of the ethanol extract and one of the isolated compounds. RESULTS: The 50% inhibitory concentration (IC(50)) of the ethanol extract was found to be 73.9 MUg/mL against leukemic U-937 cells. Good antioxidant activity (IC(50)=18.89 MUg/mL) of the ethanol extract indicated the potential of Crotalaria agatiflora as chemo preventative supplement. A bioassay guided fractionation of the ethanol extract led to the isolation of two pure compounds, namely madurensine and doronenine. Madurensine and doronenine showed moderate cytotoxicity on cancerous U-937 cells (IC(50) values: 47.97 and 29.57 M respectively). The crude extract treated U-937 cells showed definite signs of cell death during light microscopic investigation, while little apoptosis (10-20%) and necrosis (<2%) were detected in cells treated with the extract or madurensine. CONCLUSIONS: The results indicated that Crotalaria agatiflora possesses potential chemopreventative and therapeutic properties. The exact mechanism of action should still be determined in future studies. It is hypothesized that the ethanolic extract as well as madurensine induces autophagy, which in prolonged circumstances may lead to autophagic cell death. PMID- 22041106 TI - Evaluation of antihyperglycemic activity of Cocos nucifera Linn. on streptozotocin induced type 2 diabetic rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The plant Cocos nucifera Linn. (Arecaceae) is commonly known as coconut. Traditionally the juice of the young spadix when fresh is used in diarrhea and diabetes. The objective of the present study was to investigate the effect of antidiabetic activity and effect on lipid profile as well as cardioprotective effect of hydro-methanol extract of Cocos nucifera (HECN) on streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: After 72 h of STZ (50 mg/kg, b.w. i.p.) administration, animals showing plasma sugar level more than 250 mg/dl were considered as diabetic rat. Fasting blood glucose (FBG) levels were measured on 0th (after 72 h of STZ), 5th, 10th, and 15th day. On the 15th day all the animals were sacrificed and the serum biochemical parameters and antioxidant enzyme status were measured. RESULTS: HECN treated animals showed a significant reduction in FBG level as compared with diabetic control group. Serum enzyme level (SGOT, SGPT, SALP), lipid peroxidation and antioxidant enzyme level such as CAT, GSH, SOD and cholesterol and triglycerides in the HECN treated groups were restored towards normal level as compared to diabetic control groups and the values were comparable with the standard groups (glibenclamide). CONCLUSION: Improvement in the FBG and the restoration of all other biomarker as well as enzymes indicates that HECN has very good antidiabetic activity with very low side effects and provides a scientific rationale for the use as an antidiabetic agent. PMID- 22041107 TI - Oxidative modification of rat sulfotransferase 1A1 activity in hepatic tissue slices correlates with effects on the purified enzyme. AB - Mammalian cytosolic sulfotransferases (SULTs) catalyze the sulfation of xenobiotics as well as numerous endogenous molecules. The major aryl (phenol) SULT in rat liver, rSULT1A1, has been used extensively as a model enzyme for understanding the catalytic function of SULTs. Previous studies showed that purified rSULT1A1 displays significant catalytic changes in the presence of GSSG and other oxidants. In the present study, the effects of diamide [1,1'-azobis(N,N dimethylformamide)] and tert-butyl hydroperoxide (TBHP) on the activity of rSULT1A1 in rat hepatic slices were compared with the effects of these oxidants on a homogeneous preparation of the enzyme. Precision-cut hepatic slices were incubated with 10 MUM 7-hydroxycoumarin (7-HC) in the presence of varied concentrations of either diamide or TBHP. Analysis of the 7-hydroxycoumarin sulfate released into the incubation medium indicated that both oxidants significantly increased the sulfation of 7-HC, and this occurred at optimal concentrations of 5 and 10 MUM, respectively. Cellular GSH and GSSG levels in the hepatic slices were not significantly altered from control values at these concentrations of diamide and TBHP. Exposure of homogeneous rSULT1A1 to diamide or TBHP also increased the rate of sulfation of 7-HC, although the optimal concentrations of diamide and TBHP were lower (50- and 100-fold, respectively) than those required for effects with the hepatic slices. These results indicate that both diamide and TBHP may modify the rSULT1A1 in intact cells in a manner similar to that observed with the homogeneous purified enzyme. PMID- 22041108 TI - Use of baculovirus BacMam vectors for expression of ABC drug transporters in mammalian cells. AB - ATP-binding cassette (ABC) drug transporters ABCB1 [P-glycoprotein (Pgp)] and ABCG2 are expressed in many tissues including those of the intestines, the liver, the kidney and the brain and are known to influence the pharmacokinetics and toxicity of therapeutic drugs. In vitro studies involving their functional characteristics provide important information that allows improvements in drug delivery or drug design. In this study, we report use of the BacMam (baculovirus based expression in mammalian cells) expression system to express and characterize the function of Pgp and ABCG2 in mammalian cell lines. BacMam-Pgp and BacMam-ABCG2 baculovirus-transduced cell lines showed similar cell surface expression (as detected by monoclonal antibodies with an external epitope) and transport function of these transporters compared to drug-resistant cell lines that overexpress the two transporters. Transient expression of Pgp was maintained in HeLa cells for up to 72 h after transduction (48 h after removal of the BacMam virus). These BacMam-baculovirus-transduced mammalian cells expressing Pgp or ABCG2 were used for assessing the functional activity of these transporters. Crude membranes isolated from these cells were further used to study the activity of these transporters by biochemical techniques such as photo-cross-linking with transport substrate and adenosine triphosphatase assays. In addition, we show that the BacMam expression system can be exploited to coexpress both Pgp and ABCG2 in mammalian cells to determine their contribution to the transport of a common anticancer drug substrate. Collectively, these data demonstrate that the BacMam-baculovirus-based expression system can be used to simultaneously study the transport function and biochemical properties of ABC transporters. PMID- 22041109 TI - Mass balance study of [14C]eribulin in patients with advanced solid tumors. AB - This mass balance study investigated the metabolism and excretion of eribulin, a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, in patients with advanced solid tumors. A single approximately 2 mg (approximately 80 MUCi) dose of [14C]eribulin acetate was administered as a 2 to 5 min bolus injection to six patients on day 1. Blood, urine, and fecal samples were collected at specified time points on days 1 to 8 or until sample radioactivity was <=1% of the administered dose. Mean plasma eribulin exposure (627 ng . h/ml) was comparable with that of total radioactivity (568 ng Eq . h/ml). Time-matched concentration ratios of eribulin to total radioactivity approached unity in blood and plasma, indicating that unchanged parent compound constituted almost all of the eribulin-derived radioactivity. Only minor metabolites were detected in plasma samples up to 60 min postdose, pooled across patients, each metabolite representing <=0.6% of eribulin. Elimination half-lives for eribulin (45.6 h) and total radioactivity (42.3 h) were comparable. Eribulin-derived radioactivity excreted in feces was 81.5%, and that of unchanged eribulin was 61.9%. Renal clearance (0.301 l/h) was a minor component of total eribulin clearance (3.93 l/h). Eribulin-derived radioactivity excreted in urine (8.9%) was comparable with that of unchanged eribulin (8.1%), indicating minimal excretion of metabolite(s) in urine. Total recovery of the radioactive dose was 90.4% in urine and feces. Overall, no major metabolites of eribulin were detected in plasma. Eribulin is eliminated primarily unchanged in feces, whereas urine constitutes a minor route of elimination. PMID- 22041110 TI - Ghrelin in neuroendocrine tumors. AB - Ghrelin is a 28 amino acid peptide, primarily produced by the oxyntic mucosa X/A like neuroendocrine cells in the stomach. It is also found in the small intestine, hypothalamus, pituitary gland, pancreas, heart, adipose tissue, and immune system. In gastrointestinal neuroendocrine tumors (NETs) ghrelin release has been well documented. Ghrelin is a brain-gut circuit peptide with an important role in the physiological regulation of appetite, response to hunger and starvation, metabolic and endocrine functions as energy expenditure, gastric motility and acid secretion, insulin secretion and glucose homeostasis, as well as in the potential connection to the central nervous system. Recently, there has been a significant interest in the biological effects of ghrelin in NETs. In this article, we present a comprehensive review of ghrelin's expression and a brief summary of ghrelin's physiological role in NETs patients with carcinoids, type A chronic atrophic gastritis (CAG), with or without MEN-1, and with and without liver metastases. We hope, with the research reviewed here, to offer compelling evidence of the potential significance of ghrelin in NETs, as well as to provide a useful guide to the future work in this area. PMID- 22041111 TI - Conjugation of both on-axis and off-axis light in Nipkow disk confocal microscope to increase availability of incoherent light source. AB - Laser-scanning confocal microscopy has been employed for exploring structures at subcellular, cellular and tissue level in three dimensions. To acquire the confocal image, a coherent light source, such as laser, is generally required in conventional single-point scanning microscopy. The illuminating beam must be focused onto a small spot with diffraction-limited size, and this determines the spatial resolution of the microscopy system. In contrast, multipoint scanning confocal microscopy using a Nipkow disk enables the use of an incoherent light source. We previously demonstrated successful application of a 100 W mercury arc lamp as a light source for the Yokogawa confocal scanner unit in which a microlens array was coupled with a Nipkow disk to focus the collimated incident light onto a pinhole (Saito et al., Cell Struct. Funct., 33: 133-141, 2008). However, transmission efficiency of incident light through the pinhole array was low because off-axis light, the major component of the incident light, was blocked by the non-aperture area of the disk. To improve transmission efficiency, we propose an optical system in which off-axis light is able to be transmitted through pinholes surrounding the pinhole located on the optical axis of the collimator lens. This optical system facilitates the use of not only the on-axis but also the off-axis light such that the available incident light is considerably improved. As a result, we apply the proposed system to high-speed confocal and multicolor imaging both with a satisfactory signal-to-noise ratio. PMID- 22041112 TI - Conversion degrees of a colored compomer in different colors utilized by various curing times. AB - PURPOSE: Compomers are widely used in primary teeth and are manufactured in different colors in order to make dental treatment acceptable in children. The aim of this in vitro study was to evaluate the degree of conversion (DC) of different colored compomers and of compomers with various curing times. METHODS: Sixty three cylindrical samples were prepared from a colored compomer (Twinky Star). These samples were of 7 different color groups, with 9 samples of each color. Each group was divided into 3 sub-groups, according to the curing time (20 30-40 seconds) with a light emitting diode light curing unit. The DC values from 3 different regions and depths were evaluated with a Fourier Transform Infrared Spectrometer before and after curing procedures for all groups. Data were calculated by using the baseline values; statistical analyses were done by using ANOVA test. RESULTS: Significant differences in DC results before and after curing were found among the groups (P<0.05). For all curing times, the silver colored samples showed the poorest DC results, which ranged from 13% to 18%. CONCLUSIONS: It was concluded that DC values of different colors were variable. The material properties could be improved by defining the proper polymerization time for each color. PMID- 22041113 TI - Effect of light curing methods on microleakage and microhardness of different resin sealants. AB - PURPOSE: This study's purpose was to evaluate the effect of light curing methods on the microleakage and microhardness of sealants. METHODS: The Elipar Free Light 2 light emitting diode (LED) with 10- and 20-second curing times, and the Elipar 2500 halogen light with a 20-second curing time were compared. Four different sealants were used: (1) Delton Clear; (2) Delton Opaque; (3) UltraSeal XT Clear; and (4) UltraSeal XT Opaque. Specimens were fabricated in a silicone mold (2-mm thick) and cured. Knoop hardness was measured at the bottom and top surfaces. For the microleakage evaluation, 120 human molars were divided into 12 groups and sealed with the sealants and curing methods, as stated previously. The teeth were thermocycled and immersed in 2% methylene blue for 24 hours. Each tooth was sectioned and examined for dye penetration. RESULTS: There were no statistically significant differences in the microleakage of sealants polymerized by either the halogen or LED curing methods. The microhardness of sealants varied according to the type of material and curing method. CONCLUSIONS: A 10-second polymerization time with light emitting diodes was not sufficient to cure the 2-mm-thick opaque or high filler loaded sealants. Decreasing the curing time, however, had no effect on the microleakage of the sealants. PMID- 22041114 TI - Gingival health status of 2- to 15-year-old Benghazi children with type-I diabetes mellitus. AB - PURPOSE: The influence of diabetes on the risk of developing gingivitis has been the subject of much discussion in the literature. Most of the previous literature has focused on adults, with limited studies available on children. The purpose of this study was to evaluate and compare the plaque and gingival health status of diabetic children with healthy controls. METHODS: A comparative study was conducted between 72 children with type-I diabetes mellitus (average age=10.18+/ 3.91-years-old) and 72 healthy controls (average age=10.8+/-2.78- years-old). Both groups were compared statistically regarding plaque and gingival indices using the t test for equality of means. RESULTS: The experimental group showed higher mean plaque and gingival scores vs the control group. A statistically significant difference (P<.01) in plaque and gingival scores were observed between the groups in the primary, mixed, and permanent dentition. CONCLUSIONS: Higher dental plaque levels and gingival scores were observed in the diabetic children vs the nondiabetic controls. Additional care for prevention of plaque accumulation and gingivitis should be highly recommended, particularly in diabetic youth. PMID- 22041115 TI - Temporomandibular joint ankylosis surgery in a child: case report. AB - Temporomandibular joint ankylosis is one of the most significant disorders of the stomatognathic system because it causes pain associated with severe functional limitations, such as difficulty in chewing and psychological and clinical problems due to poor oral hygiene. These disorders are quite significant in children, since the treatment is even more complex due to the fact that the condylar region is a site of active growth. The earlier the diagnosis is established, the better the treatment prognosis. Ankylosis can be treated by interposition arthroplasty of the temporalis muscle fascia in conjunction with ipsilateral coronoidectomy. The purpose of the present study was to report a clinical case of temporomandibular joint ankylosis in a pediatric patient treated by interposition arthroplasty of the temporalis muscle fascia associated with coronoidectomy. PMID- 22041116 TI - Management of a case of ectodermal dysplasia: a multidisciplinary approach. AB - Ectodermal dysplasia (ED) is a rare disorder involving 2 or more of the ectodermal structures, which include the skin, hair, nails, teeth, mucus glands, and sweat glands. Each person with ectodermal dysplasia may have a different combination of defects. The most common form of ED is linked to the X chromosome and usually affects men. Another form of the disease affects men and women equally. The patient's special needs are taken into consideration in a treatment plan. The purpose of this case report was to describe the dental management of a 9-year-old boy with ectodermal dysplasia whose maxilla showed the presence of mobile, conical teeth that were unrestorable and a solitary permanent left molar, while his mandible was completely edentulous. These mobile, conical teeth were extracted, and a complete denture was constructed to restore the patient's esthetics, form, and function. PMID- 22041117 TI - Treatment of a large dentigerous cyst in a child. AB - A dentigerous cyst is a developmental odontogenic cyst that develops when fluid accumulates between the reduced enamel epithelium and the tooth crown of an unerupted tooth. Treatment modalities range from marsupialization to enucleation and are based on the premise that the pathological process can be controlled locally with minimal injury to the adjacent host structures. The purpose of this case report was to describe the diagnosis of a large expansible dentigerous cyst in an 11-year-old boy. The chosen treatment was an initial decompression to reduce the size of the osseous defect, followed by enucleation and tooth extraction. PMID- 22041118 TI - Ascorbic acid deficiency: a case report. AB - Scurvy is well known since ancient times, but it is rarely seen in the developed world today owing to the discovery of its link to the dietary deficiency of ascorbic acid. It is very uncommon in the pediatric population, and is usually seen in children with severely restricted diet attributable to psychiatric or developmental disturbances. The condition presents itself by the formation of perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We report a case of scurvy in a 10-year-old developmentally delayed boy who had a diet markedly deficient in vitamin C resulting from extremely limited food choices. He presented with debilitating bone pain, inflammatory gingival disease, and perifollicular hyperkeratosis. The diagnosis was made based on clinical and radiographic findings. The importance of diet history is emphasized. We present this case with the aim to help the clinician identify scurvy and implement treatment for a potentially fatal but easily curable disease. PMID- 22041119 TI - Surgical treatment of tongue lymphangioma in a pediatric patient: a case report. AB - Lymphangiomas are benign tumors that occur predominantly in the head and neck regions. They are very common in children and are usually diagnosed at birth or during the first years of life. Understanding their clinical features is crucial to an early diagnosis. The purpose of this paper was to report the case of a 3 year-old patient with a nodular lesion that evolved for 2 years on the tongue's dorsal surface, highlight the surgical treatment and characteristics of this kind of pathology, and explore the differential diagnosis. PMID- 22041120 TI - Maxillary reconstruction with particulate bone graft and titanium mesh: a treatment option for large complex odontoma of the maxilla. AB - Odontomas are the most common type of odontogenic tumor and are generally asymptomatic. The purpose of this paper was to describe the case of a complex odontoma in a patient who had asymptomatic swelling in the central maxillary region, along with unerupted central and lateral incisors. In this case, surgical excision of the lesion was performed and an iliac bone graft was introduced into the defect area with a titanium mesh covering up the grafted harvesting bone. After 2 years of followup, no recurrence was identified. Patient followup is still in progress to evaluate bone graft resorption, and the patient awaits complete bone development. Oral rehabilitation with an osseointegrated titanium implant is expected in the future. An option of the large complex odontoma treatment is discussed. PMID- 22041121 TI - Retrieval of concrete words involves more contextual information than abstract words: multiple components for the concreteness effect. AB - The current study used the directed forgetting paradigm in implicit and explicit memory to investigate the concreteness effect. Event-related potentials (ERPs) were recorded to explore the neural basis of this phenomenon. The behavioral results showed a clear concreteness effect in both implicit and explicit memory tests; participants responded significantly faster to concrete words than to abstract words. The ERP results revealed a concreteness effect (N400) in both the encoding and retrieval phases. In addition, behavioral and ERP results showed an interaction between word concreteness and memory instruction (to-be-forgotten vs. to-be-remembered) in the late epoch of the explicit retrieval phase, revealing a significant concreteness effect only under the to-be-remembered instruction condition. This concreteness effect was realized as an increased P600-like component in response to concrete words relative to abstract words, likely reflecting retrieval of contextual details. The time course of the concreteness effect suggests advantages of concrete words over abstract words due to greater contextual information. PMID- 22041122 TI - Detailed discussion on evidence for the further prevention of traffic fatalities in Japan: a comparison of trends in three countries. AB - The total number of traffic fatalities has decreased in recent years. To further reduce the number of traffic fatalities, details regarding traffic fatalities and various aspects of traffic accidents must be studied. Therefore, this research examined the number of traffic fatalities by age group and the number of traffic fatalities by situation in Japan from 2003 to 2007, and the percentage of traffic fatalities by age group and the percentage of traffic fatalities by situation during the same period were calculated. In addition, aspects of traffic accidents in Japan were compared with those in Germany and France, and additional measures to counter traffic accidents that need to be taken in Japan in order to further reduce the number of traffic fatalities were studied. Results indicated that in each year of the period studied the highest percentage of traffic fatalities involved the 25-64 age group in Germany and France and the 65-or-over age group in recent years in Japan. In addition, additional measures to counter traffic accidents involving the elderly are needed in Japan, Germany and France. The percentage of traffic fatalities by situation indicated that attention should be paid to 'fatalities of pedestrians' in Japan and to 'fatalities of motor vehicle occupants' in all the three countries studied. In particular, measures to counter traffic accidents leading to 'fatalities of pedestrians' must be studied further in Japan. With the above findings in mind, bodies involved in implementing measures to counter traffic accidents must formulate specific measures. PMID- 22041123 TI - Assessment of bruise age on dark-skinned individuals using tristimulus colorimetry. AB - INTRODUCTION: Studies on the ageing of bruises have been reported on Caucasians or individuals of fair ethnicity. This study focuses on bruise changes in dark skinned individuals using tristimulus colorimetry for forensic analysis in such individuals. METHODS: Eighteen subjects of South Indian or Sri-Lankan ethnicity were recruited. Subjects were bruised using a vacuum pump and then daily colour measurements were taken of the bruise using a tristimulus colorimeter. The L*a*b* readings were recorded of a control area and of the bruise until it disappeared. Two Caucasians were used for comparison. RESULTS: This study showed that, using colorimetry, bruises on dark-skinned individuals can be measured and analysed even if the bruises are unclear visually. As the bruise is beneath the skin, the colour difference DeltaL*, Deltaa* and Deltab* were calculated. All values showed a trend, indicating that the L*a*b* measuring technique is a reliable method to analyse bruises on dark-skinned individuals. Comparisons of Asian subjects and Caucasian subjects were performed. The largest difference was seen in the b* value. Statistical analysis showed that DeltaL* colour difference was the most consistent (95% CI -4.05 to -2.49) showing a significant difference between days 1-4 and 5-8. CONCLUSION: Objective assessment of bruises on dark-skinned individuals using the L*a*b* method of measuring gave reproducible results. Furthermore, the study showed that the yellowing of a bruise cannot be seen or measured with a tristimulus colorimeter on dark-skinned individuals due to the pigmentation of the skin. With further studies and more subjects, the age of bruises could potentially be assessed for use in forensic analysis. PMID- 22041124 TI - Body weight and wages: evidence from Add Health. AB - This note uses data from the National Longitudinal Study of Adolescent Health to examine the relationship between body weight and wages. Ordinary least squares (OLS) and individual fixed effects estimates provide evidence that overweight and obese white women are paid substantially less per hour than their slimmer counterparts. Two-stage least squares (2SLS) estimation confirms this relationship, suggesting that it is not driven by time-variant unobservables. PMID- 22041126 TI - High-intensity aerobic training improves endothelium-dependent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus. AB - BACKGROUND: The aim of this study is to compare the effect of physical exercise program on the endothelial function of patients with metabolic syndrome and type 2 diabetes mellitus. METHODS: Patients were randomized for high intensity aerobic training (HI: 80% maximum heart rate, n=10), low intensity aerobic training (LI: 55% of maximum heart rate, n=10) and control (n=11). Before and after 6 weeks of training, subjects performed the maximal exercise test and a study of the endothelial function, through a high resolution ultrasound of the brachial artery, which was assessed after reactive hyperemia (endothelium dependent vasodilation) and nitrate administration (endothelium independent vasodilation). RESULTS: A total of 31 patients with metabolic syndrome and type 2 diabetes mellitus were studied, with mean age of 58+/-6 years, The percentage diameter difference of the vessel after hyperemia was significantly higher for the high intensity group (HI before 2.52+/-2.85% and after 31.81+/-12.21%; LI before 3.23+/-3.52% and after 20.61+/-7.76%; controls before 3.56+/-2.33% and after 2.43+/-2.14%; p<0.05). CONCLUSIONS: High intensity aerobic training improved the functional capability and endothelium dependent vasodilator response, but it does not improve the endothelium independent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus. PMID- 22041125 TI - Increased 90-kDa ribosomal S6 kinase (Rsk) activity is protective against mutant huntingtin toxicity. AB - BACKGROUND: The 90-kDa ribosomal S6 kinase (Rsk) family is involved in cell survival. Rsk activation is regulated by sequential phosphorylations controlled by extracellular signal-regulated kinase (ERK) 1/2 and 3-phosphoinositide dependent protein kinase 1 (PDK1). Altered ERK1/2 and PDK1 phosphorylation have been described in Huntington's disease (HD), characterized by the expression of mutant huntingtin (mhtt) and striatal degeneration. However, the role of Rsk in this neurodegenerative disease remains unknown. Here, we analyzed the protein levels, activity and role of Rsk in in vivo and in vitro HD models. RESULTS: We observed increased protein levels of Rsk1 and Rsk2 in the striatum of Hdh(Q111/Q111) and R6/1 mice, STHdh(Q111/Q111) cells and striatal cells transfected with full-length mhtt. Analysis of the phosphorylation of Rsk in Hdh mice and STHdh cells showed reduced levels of phospho Ser-380 (dependent on ERK1/2), whereas phosphorylation at Ser-221 (dependent on PDK1) was increased. Moreover, we found that elevated Rsk activity in STHdh(Q111/Q111) cells was mainly due to PDK1 activity, as assessed by transfection with Rsk mutant constructs. The increase of Rsk in STHdh(Q111/Q111) cells occurred in the cytosol and in the nucleus, which results in enhanced phosphorylation of both cytosolic and nuclear Rsk targets. Finally, pharmacological inhibition of Rsk, knock-down and overexpression experiments indicated that Rsk activity exerts a protective effect against mhtt-induced cell death in STHdh(Q7/Q7) cells transfected with mhtt. CONCLUSION: The increase of Rsk levels and activity would act as a compensatory mechanism with capacity to prevent mhtt-mediated cell death. We propose Rsk as a good target for neuroprotective therapies in HD. PMID- 22041127 TI - Brain connectivity of patients with Alzheimer's disease by coherence and cross mutual information of electroencephalograms during photic stimulation. AB - Alzheimer's disease (AD) is a neurodegenerative disease, usually diagnosed by neuropsychological tests, and excluded from other cerebral diseases by brain images. An electroencephalogram (EEG) provides a means of disclosing the reduced functional couplings between brain regions that occurs with AD. In the present study, 16 probable AD patients and 15 age-matched, gender-matched normal subjects were enrolled. Spectral coherence and cross mutual information (CMI) were used to analyze EEGs during intermittent photic stimulation (PS). Ocular- and heartbeat related source components (SCs) obtained from multi-channel EEGs by the independent component analysis were discarded, and the photic-related SCs were reduced using a comb filter. The undisturbed SCs and photic-related SCs before and after photic reduction were used to reconstruct photic-preserved EEGs and photic-reduced EEGs, from which harmonic coherences (direct photic-driving response) and rhythmic coherences and CMI (indirect photic affection) were computed, respectively. Our results indicate that the rhythmic coherences (particularly in the alpha and beta bands) and CMI variables as well as the harmonic coherences (particularly related to 3-Hz PS) were significantly lower in the probable AD than in normal subjects, whereas the variables derived from the resting EEGs were not statistically significant. This finding implied that the variables obtained during PS could be used to disclose impaired intra-brain associations in probable AD. PMID- 22041128 TI - A mathematical model for simulation of early decelerations in the cardiotocogram during labor. AB - Fetal welfare during labor and delivery is commonly monitored through the cardiotocogram (CTG), the combined registration of uterus contractions and fetal heart rate (FHR). The CTG gives an indication of the main determinant of the acute fetal condition, namely its oxygen state. However, interpretation is complicated by the complex relationship between the two. Mathematical models can be used to assist with the interpretation of the CTG, since they enable quantitative modeling of the cascade of events through which uterine contractions affect fetal oxygenation and FHR. We developed a mathematical model to simulate 'early decelerations', i.e. variations in FHR originating from caput compression during uterine contractions, as mediated by cerebral flow reduction, cerebral hypoxia and a vagal nerve response to hypoxia. Simulation results show a realistic response, both for fetal and maternal hemodynamics at term, as for FHR variation during early decelerations. The model is intended to be used as a training tool for gynaecologists. Therefore 6 clinical experts were asked to rate 5 real and 5 model-generated CTG tracings on overall realism and realism of selected aspects. Results show no significant differences between real and computer-generated CTG tracings. PMID- 22041129 TI - Automated clarity assessment of retinal images using regionally based structural and statistical measures. AB - An automated image analysis system for application in mass medical screening must assess the clarity of the images before analysing their content. This is the case in grading for diabetic retinopathy screening where the failure to assess clarity could result in retinal images of people with retinopathy being erroneously classed as normal. This paper compares methods of clarity assessment based on the degradation of visible structures and based on the deviation of image properties outside expected norms caused by clarity loss. Vessel visibility measures and statistical measures were determined at locations in the image which have high saliency and these were used to obtain an image clarity assessment using supervised classification. The usefulness of the measures as indicators of image clarity was assessed. Tests were performed on 987 disc-centred and macula-centred retinal photographs (347 with inadequate clarity) obtained from the English National Screening Programme. Images with inadequate clarity were detected with 92.6% sensitivity at 90% specificity. In a set of 2000 macula-centred images (200 with inadequate clarity) from the Scottish Screening Programme, inadequate clarity was detected with 96.7% sensitivity at 90% specificity. This study has shown that structural and statistical measures are equally useful for retinal image clarity assessment. PMID- 22041130 TI - The effects of flute shape and thread profile on the insertion torque and primary stability of dental implants. AB - Easy insertion of the implant and stable bone purchase is essential for an ideal dental implantation. At the implant tip, the cutting flutes and conical profile are respectively designed to reduce insertion resistance and facilitate the initial insertion. However, the tapered tip might reduce the self-tapping and bone-purchasing abilities of the flutes and the tip threads. Using sawbone blocks as standard specimens, this study experimentally measures the insertion torque, holding power, and bending strength of eight varieties of implant (4 shapes*2 profiles). The bony contact, interfacial mechanism, and the altered shape of the flutes, at different section planes, are used to explain the experimental results. The results reveal that the bone-implant gaps at the tip region significantly suppress both the self-tapping and bone-purchasing abilities of the flutes and the tip threads. This makes initial insertion of the conical implant easier. However, the conical implant eventually requires a higher insertion torque and holding power, due to tighter bony contact, at the tail threads. The bowl-fluted design has the least flute space to store the squeezed bone chips, so both insertion torque and bending strength are significantly higher. For the conical group, the holding powers of three flute designs are nearly comparable. Overall, the conical implant with bowl flutes is the optimal design, with a lower resistance to initial insertion and higher stability, for final instrumentation. PMID- 22041131 TI - An outcome analysis of two different procedures of burr-hole trephine and external ventricular drainage in acute hydrocephalus. AB - Burr-hole trephine and insertion of external ventricular drainage (EVD) is the most common neurosurgical treatment of acute hydrocephalus. Until 2005, we performed this procedure conventionally in the operating room (OR) using a mechanical drill but in 2004 we started to use a manual drill and a skull screw (Bolt Kit System [BKS], Raumedic, Munchberg, Germany) for creating burr-holes in the Intensive Care Unit (ICU) exclusively. This retrospective study compares the outcomes after both surgical procedures of 312 consecutive patients (190 patients, conventional procedure; 122, the BKS system; total female 171, male 141; mean age 59.0 years) who suffered from acute hemorrhage-related hydrocephalus and who had undergone EVD via a frontal burr-hole from January 2004 until April 2010. We reviewed the charts for surgical procedure, number of attempted insertions, radiological signs of misplacement and procedural-related hemorrhage, cerebrospinal fluid (CSF) infection rate and shunt-dependency. The CSF infection rate, the number of attempted insertions and the procedural-related hemorrhage were significantly lower in the BKS group (p=0.034; p=0.018 and 0.015 respectively). Our data indicate that the application of the manually driven drill and the skull screw in the ICU is safe and effective. In addition, there is no need for transfer and transportation of critically ill patients from the ICU to the OR. PMID- 22041132 TI - Human papillomavirus genotypes in Iranian patients with cervical cancer. AB - The aim of this study was to determine the frequency of HPV genotypes isolated from cervical intra-epithelial neoplasia grade III and invasive carcinomas of Iranian patients. A total of 94 cases were selected in five years from 2003 to 2007. After nucleic acid purification, real-time PCR was performed by means of GP5+/GP6+ primers. Subsequently, PCR products were sequenced, on the basis of which a phylogenetic tree was constructed. Negative samples and twelve randomly selected positive samples were also typed by reverse hybridization to increase the sensitivity and to confirm the results. Of 94 evaluated samples, 7 were negative for internal control gene and were excluded from the study. The overall genotyping results of phylogenetic analysis and hybridization methods were as follows: HPV 16: 75% (65/87); HPV 18: 3% (2/87); HPV 31: 1% (1/87); HPV 45: 1% (1/87). High frequency of HPV 16 and low frequency of HPV 18 were found in this study. Information about HPV genotype distribution is important in cervical cancer screening and prevention. PMID- 22041133 TI - Evaluating the potential of the sterile insect technique for malaria control: relative fitness and mating compatibility between laboratory colonized and a wild population of Anopheles arabiensis from the Kruger National Park, South Africa. AB - BACKGROUND: The successful suppression of a target insect population using the sterile insect technique (SIT) partly depends on the premise that the laboratory insects used for mass rearing are genetically compatible with the target population, that the mating competitiveness of laboratory reared males is at least comparable to that of their wild counterparts, and that mass rearing and sterilization processes do not in themselves compromise male fitness to a degree that precludes them from successfully competing for mates in the wild. This study investigated the fitness and sexual cross-compatibility between samples of field collected and laboratory reared An. arabiensis under laboratory conditions. RESULTS: The physiological and reproductive fitness of the MALPAN laboratory strain is not substantially modified with respect to the field population at Malahlapanga. Further, a high degree of mating compatibility between MALPAN and the Malahlapanga population was established based on cross-mating experiments. Lastly, the morphological characteristics of hybrid ovarian polytene chromosomes further support the contention that the MALPAN laboratory colony and the An. arabiensis population at Malahlapanga are genetically homogenous and therefore compatible. CONCLUSIONS: It is concluded that the presence of a perennial and isolated population of An. arabiensis at Malahlapanga presents a unique opportunity for assessing the feasibility of SIT as a malaria vector control option. The MALPAN laboratory colony has retained sufficient enough measures of reproductive and physiological fitness to present as a suitable candidate for male sterilization, mass rearing and subsequent mass release of sterile males at Malahlapanga in order to further assess the feasibility of SIT in a field setting. PMID- 22041135 TI - Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans. AB - Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB 100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions. PMID- 22041136 TI - Acute abdomen in a woman with celiac disease. PMID- 22041134 TI - Fish oil -- how does it reduce plasma triglycerides? AB - Long chain omega-3 fatty acids (FAs) are effective for reducing plasma triglyceride (TG) levels. At the pharmaceutical dose, 3.4g/day, they reduce plasma TG by about 25-50% after one month of treatment, resulting primarily from the decline in hepatic very low density lipoprotein (VLDL-TG) production, and secondarily from the increase in VLDL clearance. Numerous mechanisms have been shown to contribute to the TG overproduction, but a key component is an increase in the availability of FAs in the liver. The liver derives FAs from three sources: diet (delivered via chylomicron remnants), de novo lipogenesis, and circulating non-esterified FAs (NEFAs). Of these, NEFAs contribute the largest fraction to VLDL-TG production in both normotriglyceridemic subjects and hypertriglyceridemic, insulin resistant patients. Thus reducing NEFA delivery to the liver would be a likely locus of action for fish oils (FO). The key regulator of plasma NEFA is intracellular adipocyte lipolysis via hormone sensitive lipase (HSL), which increases as insulin sensitivity worsens. FO counteracts intracellular lipolysis in adipocytes by suppressing adipose tissue inflammation. In addition, FO increases extracellular lipolysis by lipoprotein lipase (LpL) in adipose, heart and skeletal muscle and enhances hepatic and skeletal muscle beta oxidation which contributes to reduced FA delivery to the liver. FO could activate transcription factors which control metabolic pathways in a tissue specific manner regulating nutrient traffic and reducing plasma TG. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID- 22041137 TI - Pharmacogenomics of tamoxifen: roles of drug metabolizing enzymes and transporters. AB - Tamoxifen has been widely used for the prevention of recurrence in patients with hormone receptor-positive breast cancer. Tamoxifen requires metabolic activation by cytochrome P450 (CYP) enzymes for formation of active metabolites, 4 hydroxytamoxifen and endoxifen, which have 30- to 100-fold greater affinity to the estrogen receptor and the potency to suppress estrogen-dependent breast cancer cell proliferation. CYP2D6 is a key enzyme in this metabolic activation and it has been suggested that the genetic polymorphisms of CYP2D6 influence the plasma concentrations of active tamoxifen metabolites and clinical outcomes for breast cancer patients treated with tamoxifen. The genetic polymorphisms in the other drug-metabolizing enzymes, including other CYP isoforms, sulfotransferases and UDP-glucuronosyltransferases might contribute to individual differences in the tamoxifen metabolism and clinical outcome of tamoxifen therapy although their contributions would be small. Recently, involvement of a drug transporter in the disposition of active tamoxifen metabolites was identified. The genetic polymorphisms of transporter genes have the potential to improve the prediction of clinical outcome for the treatment of hormone receptor-positive breast cancer. This review summarizes current knowledge on the roles of polymorphisms in the drug-metabolizing enzymes and transporters in tamoxifen pharmacogenomics. PMID- 22041138 TI - In vitro assessment of the allelic variants of cytochrome P450. AB - The cytochrome P450 (CYP) superfamily is one of the most important groups of enzymes involved in drug metabolism. It is responsible for the metabolism of a large number of drugs. Many CYP isoforms are expressed polymorphically, and catalytic alterations of allelic variant proteins can affect the metabolic activities of many drugs. The CYP2D6, CYP2C9, CYP2C19, and CYP2B6 genes are particularly polymorphic, whereas CYP1A1, CYP1A2, CYP2E1, and CYP3A4 are relatively well conserved without common functional polymorphisms. In vitro studies using cDNA expression systems are useful tools for evaluating functional alterations of the allelic variants of CYP, particularly for low-frequency alleles. Recombinant CYPs have been successfully expressed in bacteria, yeast, baculoviruses, and several mammalian cells. Determination of CYP variant-mediated kinetic parameters (Km and Vmax) in vitro can be useful for predicting drug dosing and clearance in humans. This review focuses on the advantages and disadvantages of the various cDNA-expression systems used to determine the kinetic parameters for CYP allelic variants, the methods for determining the kinetic parameters, and the findings of in vitro studies on highly polymorphic CYPs, including CYP2D6, CYP2C9, CYP2C19, and CYP2B6. PMID- 22041139 TI - A recent update of pharmacogenomics in drug-induced severe skin reactions. AB - In some adverse drug reactions (ADRs), genetic predisposition plays a significant role in pathogenesis, and the skin is the most frequently reported target. These severe cutaneous ADRs include bullous fixed drug eruptions (FDE), acute generalized exanthematous pustulosis (AGEP), drug-induced hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The putative contribution of individual effector cells in drug hypersensitivity is briefly mentioned. To trigger these drug hypersensitivities, certain class I HLA alleles (e.g., HLA-A and HLA-B alleles) and certain class II HLA alleles (e.g., HLA-DR alleles) have been recently found to be the genetic determinants. One of the best characterized examples mentioned in this article is HLA-B*1502 to determine the incidence of carbamazepine-induced SJS. How drugs are processed and presented by these HLA alleles to activate immune responses has been explained by several hypotheses. Further implication of pharmagenomic findings to prevent drug-induced severe skin reactions can be achieved by pre screening putative risk HLA alleles before using drugs. PMID- 22041140 TI - Combination of capillary electrophoresis, molecular modelling and nuclear magnetic resonance to study the interaction mechanisms between single-isomer anionic cyclodextrin derivatives and basic drug enantiomers in a methanolic background electrolyte. AB - In order to improve our knowledge of the mechanisms of enantiomer recognition pattern in nonaqueous systems, an approach combining nonaqueous CE (NACE), molecular modelling and NMR was undertaken. Bupivacaine and propranolol were selected as model compounds and their interactions with two single-isomer highly charged beta-CD derivatives, namely heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-CD (HDMS-beta-CD) and heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-CD (HDAS-beta-CD), were studied. The CD-bupivacaine complexes were evaluated by 2-D Rotating-frame Overhauser Effect SpectroscopY (ROESY) experiments. From these experiments, it can be assumed that inclusion complexes are not formed, whatever the CD derivative used. Molecular modelling was performed at the RHF/MINI-1 or B3LYP/6 31G(d) level. External as well as inclusion type complexes with the alkyl chain of propranolol into both CD cavities were located. Interaction energies calculated for bupivacaine and propranolol correlated with the enantiomer migration order observed in the NACE experiments using both anionic CD derivatives. The interaction of propranolol with HDMS-beta-CD or HDAS-beta-CD gives rise to a family of external and inclusion complexes in which some are more probably obtained. PMID- 22041141 TI - Combination of corona discharge ion mobility spectrometry with a novel reagent gas and two immiscible organic solvent liquid-liquid-liquid microextraction for analysis of clomipramine in biological samples. AB - A novel and sensitive method based on combination of two immiscible organic solvents hollow fiber-based liquid-liquid-liquid microextraction and corona discharge ion mobility spectrometry (HF-LLLME-CD-IMS) was employed for the analysis of clomipramine in human urine and plasma. The effect of formic, acetic and propionic acid as the reagent gas (dopant) on the corona discharge ion mobility signal was investigated. The influence of dopant amount was also studied. Optimum mass flow rates of the dopants were 3.7, 1.1 and 1.0 MUmol min( 1) for formic, acetic and propionic acid, respectively. Experimental parameters influencing the extraction efficiency of HF-LLLME, such as NaOH concentration as donor solution, ionic strength of the sample, stirring rate, and extraction time were investigated and optimized. Under the optimum conditions, analytical parameters such as linearity, precision and limit of detection were also evaluated. The linear dynamic range was from 1 to 100 MUg L(-1) (r(2)=0.9980) and the limit of detection was 0.35 MUg L(-1). Intra- and inter-day precisions were satisfactory with a relative standard deviation (RSD) of 5.9 and 6.7%, respectively. The proposed method was satisfactorily applied for the determination of clomipramine in human plasma and urine. PMID- 22041142 TI - Comprehensive separation and analysis of alkaloids from Stephania yunnanensis by counter-current chromatography coupled with liquid chromatography tandem mass spectrometry analysis. AB - The polar compounds such as alkaloid compounds are important bioactive components in traditional Chinese medicines. In present study, a comprehensive method for separation and analysis of polar compounds from the polar fraction of traditional Chinese medicine Stephania yunnanensis was established. Both the major components and minor components were analyzed by counter-current chromatography combined with liquid chromatography tandem mass spectrometry (LC-MS(n)). From 50 mg polar fraction of crude extract, 15.2mg corydine and 4.8 mg stepharine with purities over 90% were successfully separated via a polar solvent system n-butanol: methanol: water (4:1:5, v/v) with 10 mM NaOH as an additive in the lower phase, in one step operation. Their structures were further identified by 1H NMR and FTICR-MS. Besides, three minor components were identified by HPLC-MS(n) based on the fragmentation behavior of the purified compounds. PMID- 22041143 TI - Assessment of chiral stationary phases for suitability for combined enantiomeric impurity/related substances assays. AB - Chiral stationary phases (CSP) for LC had a major impact on pharmaceutical R&D when they first became commercially available in the 1980s. Even although the use of CSP in pharmaceutical R&D is now very much a mature area, there is still scope for using CSP more effectively to bring about efficiencies. One such instance is the possibility of combining the chiral LC test for the level of a trace enantiomeric impurity in a chiral drug substance and the LC test for related substances into one test. It was envisaged that this could be achieved by carrying out reversed-phase LC on an ODS silica/CSP coupled column system. In evaluating Chiralpak QD-AX, Cyclobond I 2000 DNP and Whelk-O1 CSP using a polar organic - aqueous mobile phase it was found that the Whelk-O1 CSP had good achiral selectivity, the required match of retentivity with the ODS silica material, ACE 5 C18 and also exhibited an encouraging degree of enantioselectivity in the reversed-phase mode. Following consideration of the selectivity of the ACE 5 C18 and Whelk-O1 phases it became apparent that it might be possible to achieve the desired goal of achieving both the enantiomeric impurity and related substances separations in one system by using the Whelk-O1 CSP on its own. This was subsequently demonstrated to be the case using S naproxen, laevokalim and S-flurbiprofen as illustrative examples. PMID- 22041144 TI - 'Clinical scaphoid fracture': is it time to abolish this phrase? AB - INTRODUCTION: Most patients with post-traumatic painful wrists and negative radiographs are treated as having a clinical scaphoid fracture. Such cases are usually followed up with repeat radiographs. If the radiographs are inconclusive further imaging is done. However, this traditional approach results in the vast majority of patients being unnecessarily immobilised for an unspecified period, leading to loss of productivity and income to the patient and the community. A number of studies have highlighted the use of early CT or MRI scans to identify these fractures. The aim of this study was to evaluate our current practice in managing patients with suspected fractures of the scaphoid. PATIENTS AND METHODS: A retrospective audit was carried out. The period studied was from January to August 2008. Fifty consecutive patients who were investigated for occult fractures of the scaphoid were included. RESULTS: 92% of the patients studied had a repeat radiograph in the fracture clinic. 84% of the patients had their wrists immobilised in a cast while awaiting further imaging. Only 6% had confirmed fracture of the scaphoid; all of these healed uneventfully. 76% of patients with negative scans had their wrists immobilised for an average period of 30.63 days. CONCLUSIONS: It is time we rethink this dogmatic approach to patients with clinical signs but negative radiographs. We recommend that patients with a painful wrist following an injury and negative radiographs should be referred early to an appropriate clinician and earlier recourse to advanced imaging should be advocated. PMID- 22041145 TI - The role of a multidisciplinary pre-assessment clinic in reducing mortality after complex orthopaedic surgery. AB - INTRODUCTION: This paper describes an audit loop. The aim of this study was to audit the effect of a specialised preoperative anaesthetic assessment clinic after hip and knee arthroplasty and revision arthroplasty. PATIENTS AND METHODS: We studied patients undergoing hip and knee surgery (arthroplasty and revision arthroplasty). We collected data concerning postoperative admissions to the high dependency unit (HDU), intensive care unit (ICU) and post-anaesthesia care unit (PACU) (planned and unplanned rates of admission, length of stay). We also noted mortality. In the first part of the study (April 2005 to March 2006) we studied 298 patients. All patients were assessed independently by an anaesthetist on the day of surgery. A multidisciplinary preoperative assessment clinic commenced in April 2006. After this date all patients were assessed preoperatively by a multidisciplinary anaesthetic lead team. In the second part of the study (May 2006 to April 2009) a further 1,147 arthroplasty patients were studied. Data were again collected regarding HDU, ICU, PACU and mortality, as noted above. RESULTS: We found statistically significant (p = 0.001) reductions in the admissions to PACU (22% down to 10%) and in mortality (6.1% down to 1.2%) after the introduction of the pre-assessment clinic. There was also a statistically significant (p = 0.01) reduction in the HDU length of stay (2.1 days to 1.6 days), ICU unplanned admissions (1.3% to 0.4%) and the ICU length of stay (2.3 to 1.9 days). We estimated cost savings of nearly L50,000 in the second part of the study. This is based on the average decrease in HDU and ICU length of stay. CONCLUSIONS: We recommend the use of a multidisciplinary pre-assessment clinic for complex orthopaedic surgery. PMID- 22041146 TI - Face, content and construct validity of a virtual reality simulator for robotic surgery (SEP Robot). AB - INTRODUCTION: This study aims to establish face, content and construct validation of the SEP Robot (SimSurgery, Oslo, Norway) in order to determine its value as a training tool. SUBJECTS AND METHODS: The tasks used in the validation of this simulator were arrow manipulation and performing a surgeon's knot. Thirty participants (18 novices, 12 experts) completed the procedures. RESULTS: The simulator was able to differentiate between experts and novices in several respects. The novice group required more time to complete the tasks than the expert group, especially suturing. During the surgeon's knot exercise, experts significantly outperformed novices in maximum tightening stretch, instruments dropped, maximum winding stretch and tool collisions in addition to total task time. A trend was found towards the use of less force by the more experienced participants. CONCLUSIONS: The SEP robotic simulator has demonstrated face, content and construct validity as a virtual reality simulator for robotic surgery. With steady increase in adoption of robotic surgery world-wide, this simulator may prove to be a valuable adjunct to clinical mentorship. PMID- 22041149 TI - Use of a modified Bradford sling for the positioning of orthopaedic patients. PMID- 22041147 TI - Intraoperative red blood cell salvage and autologous transfusion during open radical retropubic prostatectomy: a cost-benefit analysis. AB - INTRODUCTION: Open radical retropubic prostatectomy (RRP) has an average blood loss of over 1,000 ml. This has been reported even from high volume centres of excellence. We have looked at the clinical and financial benefits of using intraoperative cell salvage (ICS) as a method of reducing the autologous blood transfusion requirements for our RRP patients. MATERIALS AND METHODS: Group A comprised 25 consecutive patients who underwent RRP immediately prior to the acquisition of a cell saver machine. Group B consisted of the next 25 consecutive patients undergoing surgery using the Dideco Electa (Sorin Group, Italy) cell saver machine. Blood transfusion costs for both groups were calculated and compared. RESULTS: The mean postoperative haemoglobin was similar in both groups (11.1 gm/dl in Group A and 11.4 gm/dl in Group B). All Group B patients received autologous blood (average 506 ml, range: 103-1,023 ml). In addition, 5 patients (20%) in Group B received a group total of 16 units (average 0.6 units) of homologous blood. For Group A the total cost of transfusing the 69 units of homologous blood was estimated as L9,315, based on a per blood unit cost of L135. This cost did not include consumables or nursing costs. CONCLUSIONS: We found no evidence that autologous transfusions increased the risk of early biochemical relapse or of disease dissemination. ICS reduced our dependence on donated homologous blood. PMID- 22041150 TI - An easy, low-cost method for achieving adequate facial hair coverage for surgeons. PMID- 22041151 TI - A simple method to prevent spectacle lenses misting up on wearing a face mask. PMID- 22041152 TI - Stapled mesh stoma reinforcement technique (SMART)--a procedure to prevent parastomal herniation. PMID- 22041153 TI - Yarl vein flap fistuloplasties for juxta-anastomotic stenoses. PMID- 22041154 TI - A simple, cosmetically superior method of securing a post-surgical drain in facial surgery. PMID- 22041155 TI - The use of ink to define the position of intra-osseous wire suture apertures in bone fixation. PMID- 22041156 TI - Intra-operative ultrasound localisation of a parathyroid adenoma. PMID- 22041157 TI - A technique for bone grafting tibial and femoral tunnels in revision anterior cruciate ligament reconstruction. PMID- 22041158 TI - Simple technique to reduce stoma-bowel size discrepancy. PMID- 22041159 TI - Fingerless gloves for hand trauma cases. PMID- 22041160 TI - Bare below the elbows. PMID- 22041161 TI - Minimising the risk of extensor pollicis longus rupture following volar plate fixation of distal radius fractures: a cadaveric study. PMID- 22041162 TI - Absorbable or non-absorbable sutures? PMID- 22041163 TI - White cell count and C-reactive protein measurement in patients with possible appendicitis. PMID- 22041164 TI - GABAergic neurosteroids: the "endogenous benzodiazepines" of acute liver failure. AB - Acute liver failure (ALF) or fulminant hepatic failure represents a serious life threatening condition. ALF is characterized by a significant liver injury that leads to a rapid onset of hepatic encephalopathy (HE). In ALF, patients manifest rapid deterioration in consciousness leading to hepatic coma together with an onset of brain edema which induces high intracranial pressure that frequently leads to herniation and death. It is well accepted that hyperammonemia is a cardinal, but not the sole, mediator in the pathophysiology of ALF. There is increasing evidence that neurosteroids, including the parent neurosteroid pregnenolone, and the progesterone metabolites tetrahydroprogesterone (allopregnanolone) and tetrahydrodeoxycorticosterone (THDOC) accumulate in brain in experimental models of ALF. Neurosteroids in ALF represent good candidates to explain the phenomenon of "increased GABAergic tone" in chronic and ALF, and the beneficial effects of benzodiazepine drugs. The mechanisms that trigger brain neurosteroid changes in ALF are not yet well known, but could involve partially de novo neurosteroidogenesis following activation of the translocator protein (TSPO). The factors that contribute to TSPO changes in ALF may include ammonia and cytokines. It is possible that increases in brain levels of neurosteroids in ALF may result in auto-regulatory mechanisms where hypothermia may play a significant role. Possible mechanisms that may involve neurosteroids in the pathophysiology of HE, and more speculatively in brain edema, and inflammatory processes in ALF are suggested. PMID- 22041165 TI - Immobilized Candida antarctica lipase B: Hydration, stripping off and application in ring opening polyester synthesis. AB - This work reviews the stripping off, role of water molecules in activity, and flexibility of immobilized Candida antarctica lipase B (CALB). Employment of CALB in ring opening polyester synthesis emphasizing on a polylactide is discussed in detail. Execution of enzymes in place of inorganic catalysts is the most green alternative for sustainable and environment friendly synthesis of products on an industrial scale. Robust immobilization and consequently performance of enzyme is the essential objective of enzyme application in industry. Water bound to the surface of an enzyme (contact class of water molecules) is inevitable for enzyme performance; it controls enzyme dynamics via flexibility changes and has intensive influence on enzyme activity. The value of pH during immobilization of CALB plays a critical role in fixing the active conformation of an enzyme. Comprehensive selection of support and protocol can develop a robust immobilized enzyme thus enhancing its performance. Organic solvents with a log P value higher than four are more suitable for enzymatic catalysis as these solvents tend to strip away very little of the enzyme surface bound water molecules. Alternatively ionic liquid can work as a more promising reaction media. Covalent immobilization is an exclusively reliable technique to circumvent the leaching of enzymes and to enhance stability. Activated polystyrene nanoparticles can prove to be a practical and economical support for chemical immobilization of CALB. In order to reduce the E-factor for the synthesis of biodegradable polymers; enzymatic ring opening polyester synthesis (eROPS) of cyclic monomers is a more sensible route for polyester synthesis. Synergies obtained from ionic liquids and immobilized enzyme can be much effective eROPS. PMID- 22041166 TI - From short peptides to nanofibers to macromolecular assemblies in biomedicine. AB - In the last few years, a variety of self-assembling short peptides that consist exclusively of simple amino acids have been designed and modified. These peptides exhibit self-assembling dynamic behaviors. At the molecular structural level, they form alpha-helical, beta-sheet and beta-hairpins structures in water. These structures further undergo spontaneous assembly to form nanofibers which aggregate into supramolecular scaffolds that entrap large volumes of water. Furthermore, nanostructures and supramolecular structures that self-organized from these short peptides also have a broad spectrum of biotechnological applications. They are useful as biological materials for 2D and 3D tissue cell cultures, regenerative and reparative medicine, tissue engineering as well as injectable drug delivery matrices that gel in situ. We have endeavored to do a comprehensive review of short peptides that form nanofibrous hydrogels. In particular, we have focused on recent advances in peptide assembly motifs and applications. PMID- 22041167 TI - Clinical characteristics of urosepsis caused by extended-spectrum beta-lactamase producing Escherichia coli or Klebsiella pneumonia and their emergence in the community. AB - BACKGROUND: The purpose of this study is to delineate clinical characteristics of urosepsis caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) in different clinical settings, with an emphasis on community-acquired infections. METHODS: A retrospective study was conducted at two medical centers in Taiwan. From May 2002 to August 2007, clinical data of adults with urosepsis caused by ESBL-EK were collected. Patients were categorized into three groups according to the place of acquisition. Baseline characteristics, microbiological data and clinical outcomes were compared. RESULTS: Ninety-three cases of ESBL-EK urosepsis were included. Their mean age was 69.4 years, and 48.4% were men. Eleven (11.8%), 41 (44.1%), and 41 (44.1%) patients were categorized as having community-acquired, healthcare associated, and hospital-acquired infections, respectively. Cases of ESBL-EK urosepsis from different settings shared similar characteristics in terms of age, gender, comorbidity and resistance profiles of bacterial strains. Of the bacterial isolates, 75% and 38.7% were resistant to fluoroquinolones and aminoglycosides, respectively. Cases of community-acquired urosepsis had a lower disease severity than those acquired in healthcare facilities or hospitals. Of note, there was no case fatality in 11 cases of community-acquired urosepsis and, in contrast, a crude mortality rate of 41.5% was found among adults with hospital acquired urosepsis (p < 0.001). CONCLUSION: A limited number of adults with community-acquired urosepsis caused by ESBL-EK in the present study had a favorable outcome. Nonetheless, clinicians should be cautious of the emergence of urinary tract infections caused by ESBL-producers in the community setting. PMID- 22041168 TI - Staphylococcus lugdunensis endocarditis with isolated tricuspid valve involvement. AB - Staphylococcus lugdunensis is often misidentified as S aureus and as a rare cause of infective endocarditis. The clinical course of S lugdunensis endocarditis is aggressive and the mortality rate is high in contrast to S epidermidis endocarditis. Most reported cases of S lugdunensis endocarditis have involved mitral or aortic valves. Herein, we present a case with isolated tricuspid endocarditis due to S lugdunensis. PMID- 22041169 TI - How blind dates, internet dating, and facebook can inform the building of effective organizational partnerships. AB - To have a significant impact on public health, partnerships are essential - especially among researchers and organizations that can translate such research into action. Based on the experience of YMCA of the USA, this commentary describes how to develop a partnership strategy. It also highlights the opportunities and challenges associated with developing partnerships and translating theory into action. PMID- 22041170 TI - Targeting pancreatic cancer with a G-quadruplex ligand. AB - The integrity of telomeres in most cancer cells is maintained by the action of the telomerase enzyme complex, which catalyzes the synthesis of telomeric DNA repeats in order to replace those lost during replication. Telomerase is especially up-regulated in metastatic cancer and is thus emerging as a major therapeutic target. One approach to telomerase inhibition involves the sequestration of the single-stranded 3' ends of telomeric DNA into higher-order quadruplex structures. We have recently shown that tetra-substituted naphthalene diimide compounds are potent quadruplex-stabilizing molecules with telomerase inhibitory activity in cells. We show here that one such compound, BMSG-SH-3, which has been optimized by computer modeling, has significant in vivo antitumor activity against a model for pancreatic cancer, a cancer that is especially resistant to current therapies. A large reduction in telomerase activity in treated tumors was observed and the naphthalene diimide compound was found to be selectively localized in the treated tumors. We find that the expression of the therapeutically important chaperone protein HSP90, a regulator of telomerase is also reduced in vivo by BMSG-SH-3 treatment. The compound is a potent stabilizer of two G-quadruplex sequences found in the promoter region of the HSP90 gene, as well as a G-quadruplex from human telomeric DNA. It is proposed that the simultaneous targeting of these quadruplexes may be an effective anti-tumor strategy. PMID- 22041171 TI - Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors. AB - In a previous paper we identified several 1-aryl-6,7-dimethoxy-1,2,3,4 tetrahydroisoquinoline-2-sulfonamides that displayed inhibitory effects toward selected carbonic anhydrase isozymes at micromolar concentration. In order to deepen the structure-activity relationships (SARs) and identify novel compounds with improved activity, we synthesized a series of monomethoxy analogues of the previously investigated dimethoxy derivatives. The evaluation of biological profile has been focused on in vitro effects against several CA isoforms. The new monomethoxy derivatives showed higher hCA inhibitory effects against several isoforms compared to the dimethoxy analogues. Particularly, some of these compounds (e.g., 1b and 1h) showed low nanomolar K(I) values and excellent selectivity for hCA IX and hCA XIV versus hCA I and II inhibition. PMID- 22041172 TI - Benzenediol-berberine hybrids: multifunctional agents for Alzheimer's disease. AB - We designed and synthesized a series of hybrid molecules, in an effort to identify novel multifunctional drug candidates for Alzheimer's disease (AD), by reacting berberine with benzenediol, melatonin, and ferulic acid. The products were evaluated for: (i) the ability to inhibit multiple cholinesterases (ChEs); (ii) the capacity to prevent amyloid beta (Abeta) aggregation; and (iii) antioxidant activity. All of the derivatives were better antioxidants, and inhibited Abeta aggregation to a greater extent, than the lead compound, berberine. Two of the hybrids, in particular, have the potential to be excellent candidates for AD therapy: the berberine-pyrocatechol hybrid (compound 8) was a much better inhibitor of acetylcholinesterase (AChE) than unconjugated berberine (IC(50): 0.123 vs 0.374 MUM); and the berberine-hydroquinone hybrid (compound 12) displayed high antioxidant activity, could inhibit AChE (IC(50) of 0.460 MUM), and had the greatest ability to inhibit Abeta aggregation. PMID- 22041173 TI - Design, synthesis, and biological evaluation of a novel series of bisintercalating DNA-binding piperazine-linked bisanthrapyrazole compounds as anticancer agents. AB - A series of bisintercalating DNA binding bisanthrapyrazole compounds containing piperazine linkers were designed by molecular modeling and docking techniques. Because the anthrapyrazoles are not quinones they are unable to be reductively activated like doxorubicin and other anthracyclines and thus they should not be cardiotoxic. The concentration dependent increase in DNA melting temperature was used to determine the strength of DNA binding and the bisintercalation potential of the compounds. Compounds with more than a three-carbon linker that could span four DNA base pairs achieved bisintercalation. All of the bisanthrapyrazoles inhibited human erythroleukemic K562 cell growth in the low to submicromolar concentration range. They also strongly inhibited the decatenation activity of topoisomerase IIalpha and the relaxation activity of topoisomerase I. However, as measured by their ability to induce double strand breaks in plasmid DNA, the bisanthrapyrazole compounds did not act as topoisomerase IIalpha poisons. In conclusion, a novel group of bisanthrapyrazole compounds were designed, synthesized, and biologically evaluated as potential anticancer agents. PMID- 22041174 TI - Synthesis and activity of new macrolones: conjugates between 6(7)-(2'-aminoethyl) amino-1-cyclopropyl-3-carboxylic acid (2'-hydroxyethyl) amides and 4"-propenoyl azithromycin. AB - A set of novel macrolones containing the flexible C8 basic linker and quinolone 3 (2'-hydroxyethyl)carboxamido group has been prepared and structurally characterized by NMR and IR spectroscopy, mass spectrometry and molecular modeling. The new compounds were evaluated in vitro against a panel of erythromycin-susceptible and erythromycin-resistant Gram-positive and Gram negative bacterial strains. Compared to azithromycin, most of the compounds exhibited improved in vitro potency against the key respiratory pathogens. PMID- 22041175 TI - Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors. AB - Pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives are new chemical entities with good and attractive druglikeness properties. A series of pyrazolo-pyrido-diazepine dione analogs demonstrated to be particularly amenable to lead optimization through a couple of cycles in order to improve specificity for isoforms Nox4 and Nox1 and had excellent pharmacokinetic parameters by oral route. Several molecules such as compound 7c proved to be highly potent in in vitro assays on human lung fibroblasts differentiation as well as in curative murine models of bleomycin-induced pulmonary fibrosis with superior efficiency over Pirfenidone. Pyrazolo-pyrido-diazepine dione derivatives targeting Nox4 and Nox1 isoforms appear highly promising therapeutics for the treatment of idiopathic pulmonary fibrosis. PMID- 22041176 TI - [Influence of age on antibody titers following rabies post-exposure prophylaxis]. PMID- 22041177 TI - [Effects of food restriction imposed to adult rats on the bone growth and the histological structure of the thyroid in their youth]. AB - STUDY PURPOSE: Our objective was the study of the development and the maturation of pups whose mothers were subjected to intermittent fasting. MATERIALS AND METHODS: Eight pregnant female Wistar rats were distributed into two groups of four adult females. The rats of the first group were subjected to intermittent fasting beginning on the 14th day of gestation and continued 21 days after parturition. The rats of the second group were normally fed. The young of both groups of rats were sacrificed at the age of 21 days. RESULTS: The pups of the female rats submitted to food restriction showed a reduction of the body weight ( 35%), of the thyroid iodine content (P<0.001) and of segment thyroxin (P<0.05). The histological study revealed that these pups presented colloid depletion of this follicular thyroid, non-anastomosing trabeculae, cortical bone thinning, decreased bone mineral content, absence of osteoid formation and decreased number of osteoclasts. CONCLUSION: Dietary restriction imposed on adult rats, from gestation, led to the installation in their pups of a state of malnutrition and a description of thyroid histology. This thyroid abnormality is associated with hypothyroidism that led, at least in part, to the collapse of the ability to regulate bone remodeling. PMID- 22041178 TI - Ultrasound imaging for the rheumatologist XXXV. Sonographic assessment of the foot in patients with osteoarthritis. AB - OBJECTIVES: The aims of our study were to investigate the prevalence of ultrasound (US) abnormalities in the foot of patients with osteoarthritis (OA) and to compare them with clinical findings. METHODS: Consecutive patients with foot OA were investigated by clinical and US examinations. Bilateral US of the midfoot and forefoot joints was performed by using a Logiq9 machine, equipped with a multi-frequency linear probe, operating at 14 MHz; in addition, power Doppler was applied (frequency 7.5 MHz; gain 50%; PRF 750 Hz). Clinical evaluation included the registration of demographic data, disease duration, current treatment undergone, joint swelling and tenderness. US study included the assessment of both inflammatory (joint effusion, synovial hypertrophy, local pathologic vascularisation at PD, big-toe bursitis) and structural (osteophytes, MTP joints subluxation) abnormalities. RESULTS: One hundred patients were studied. At midfoot level, clinical examination demonstrated signs suggestive for joint inflammation (tenderness and/or swelling) in at least one joint in 43/200 feet (21.5%) of 23 patients; US showed inflammatory abnormalities in 87/200 feet (43.5%) of 63 patients and structural lesions in 100/200 feet (50%) of 70 patients. At forefoot level, clinical examination found inflammatory signs in at least one joint in 128 feet (64%) of 64 patients; US showed inflammatory abnormalities in at least one joint in 176 feet (88%) of 88 patients and structural lesions in 189 feet (86%) of 86 patients. CONCLUSIONS: US is a useful imaging tool for analysing both inflammatory and structural damage lesions at foot joints level in OA. In addition, it demonstrated to be more sensitive than clinical examination in the detection of inflammatory abnormalities. PMID- 22041179 TI - Association between Th-17 cytokine profile and clinical features in patients with spondyloarthritis. AB - OBJECTIVES: In recent years, a substantial amount of information has become available on the relationship between cytokines associated with the Th-17 profile and the development of spondyloarthritis (SpA). The purpose of this study was to evaluate inflammation markers in serum and synovial fluid (SF) and levels of cytokines related to the Th-17 profile in patients with different subtypes of SpA and healthy subjects. METHODS: We evaluated this cytokine profile in light of the clinical activity of the disease in 62 patients. Serum cytokine levels (IL-17, IL 6, IL-1 alpha, TNF alpha, IFN-gamma) were measured by flow cytometry. IL-23, serum amyloid (SAA) and metalloproteinase 3 (MMP-3) were measured with ELISA. In all patients, clinical evaluation was performed using the activity and function indexes of the disease. RESULTS: A comparison showed that IL-17, IL-23, IL-1 alpha, IL-6, and TNF-alpha levels were significantly higher in the serum of SpA patients than healthy subjects (HS), and there were no differences among SpA subtypes. In SF we found higher concentrations of cytokines, but only IL-23 showed significant differences (p<0.05). We found a relationship between enthesitis and peripheral involvement and serum IL-17 levels (9 to 63 pg / ml). There was a correlation between levels above 63 pg/ml and a history of infection. Higher levels of IL-23 in synovial fluid could suggest local amplification of the Th-17 cytokine profile. CONCLUSIONS: These results suggest a possible relationship between IL-17 and enthesis involvement in SpA. PMID- 22041180 TI - Etanercept in spondyloarthropathies. Part I: current evidence of efficacy. AB - Etanercept is a recombinant soluble tumour necrosis factor alpha receptor administered subcutaneously at the dose of 50 mg weekly (or 25 mg/twice weekly) for the treatment of the main chronic arthritides: rheumatoid arthritis and spondyloarthropathies. It shows high qualities in terms of efficacy and manageability. Favourable results were reported in all localisations of spondyloarthropathies: axial disease, peripheral arthritis, and enthesitis. In particular, several studies demonstrated its efficacy on the clinical and functional indicators of ankylosing spondylitis. Similar data were also reported for psoriatic arthritis in which, in addition, a significant reduction in the progression of erosive damages was widely described. Furthermore, although only a few studies are available, very interesting results have been obtained in patients suffering from undifferentiated spondyloarthropathies and severe enthesitis. PMID- 22041181 TI - Etanercept in spondyloarthopathies. Part II: safety and pharmacoeconomic issues. AB - Etanercept (ETN) and other anti-TNF-alpha agents have revolutionised the management of spondyloarthropathies (SpA). With the increasingly widespread and prolonged use of these drugs an assessment of their long-term safety is extremely important. An additional concern regarding biological agents is their higher costs compared with conventional drugs. We examined safety data regarding ETN from clinical reports, clinical trials, review articles, databases and registries. In addition, evidence was reviewed about the cost effectiveness of ETN in the treatment of patients with SpA. Our review suggests that ETN is well tolerated as long-term, continuous treatment of SpA with a favourable risk benefit ratio maintained from 4 to 5 years. Diversity in structure and mode of action could explain some differences in the safety profile of ETN with respect to the other anti-TNF agents. In particular, ETN is less immunogenic and is less likely to induce tuberculosis re-activation than the other TNF-alpha antagonists. Although ETN is considerably more expensive than conventional therapy, it reduces direct and indirect costs associated to SpA by improving disease activity and quality of life. Recent pharmacoeconomic studies have demonstrated its cost effectiveness in the treatment of SpA. PMID- 22041182 TI - Control of hypothalamic-pituitary-adrenal stress axis activity by the intermediate conductance calcium-activated potassium channel, SK4. AB - The anterior pituitary corticotroph is a major control point for the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the neuroendocrine response to stress. Although corticotrophs are known to be electrically excitable, ion channels controlling the electrical properties of corticotrophs are poorly understood. Here, we exploited a lentiviral transduction system to allow the unequivocal identification of live murine corticotrophs in culture. We demonstrate that corticotrophs display highly heterogeneous spontaneous action potential firing patterns and their resting membrane potential is modulated by a background sodium conductance. Physiological concentrations of corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) cause a depolarization of corticotrophs, leading to a sustained increase in action potential firing. A major component of the outward potassium conductance was mediated via intermediate conductance calcium-activated (SK4) potassium channels. Inhibition of SK4 channels with TRAM-34 resulted in an increase in corticotroph excitability and exaggerated CRH/AVP-stimulated ACTH secretion in vitro. In accordance with a physiological role for SK4 channels in vivo, restraint stress-induced plasma ACTH and corticosterone concentrations were significantly enhanced in gene-targeted mice lacking SK4 channels (Kcnn4(-/-)). In addition, Kcnn4(-/-) mutant mice displayed enhanced hypothalamic c-fos and nur77 mRNA expression following restraint, suggesting increased neuronal activation. Thus, stress hyperresponsiveness observed in Kcnn4(-/-) mice results from enhanced secretagogue-induced ACTH output from anterior pituitary corticotrophs and may also involve increased hypothalamic drive, thereby suggesting an important role for SK4 channels in HPA axis function. PMID- 22041183 TI - Heterosynaptic long-term potentiation at interneuron-principal neuron synapses in the amygdala requires nitric oxide signalling. AB - Long-lasting changes of synaptic efficacy are thought to be a prerequisite for memory formation and maintenance. In the basolateral complex of the amygdala (BLA), one of the main regions for fear and extinction learning of the brain, various forms of long-term potentiation (LTP) have been described for excitatory glutamatergic synapses. In contrast, little is known about the mechanisms of LTP at inhibitory GABAergic synapses. Here we provide evidence that (1) LTP at inhibitory GABAergic synapses (LTP(i)) between inhibitory interneurons and principal neurons (PNs) can be induced by theta-burst stimulation (TBS), (2) this LTP(i) is prevented by AMPA- or NMDA-receptor antagonists, and (3) this LTP(i) is abolished by the NO synthase (NOS) inhibitor L-NAME or the NO scavenger PTIO, and thus is critically dependent on nitric oxide (NO) signalling. These findings are corroborated by immunocytochemical stainings for neuronal (n) NOS, which revealed the existence of nNOS-positive neurons and fibres in the BLA. We conclude that LTP of GABAergic synaptic transmission to PNs is induced by activation of AMPA and NMDA receptors at glutamatergic synapses and subsequent retrograde NO signalling to enhance GABAergic transmission. This form of LTP at GABAergic synapses comprises a novel form of heterosynaptic plasticity within the BLA, apt to shape conditioned fear responses. PMID- 22041184 TI - Fast calcium and voltage-sensitive dye imaging in enteric neurones reveal calcium peaks associated with single action potential discharge. AB - Slow changes in [Ca(2+)](i) reflect increased neuronal activity. Our study demonstrates that single-trial fast [Ca(2+)](i) imaging (>=200 Hz sampling rate) revealed peaks each of which are associated with single spike discharge recorded by consecutive voltage-sensitive dye (VSD) imaging in enteric neurones and nerve fibres. Fast [Ca(2+)](i) imaging also revealed subthreshold fast excitatory postsynaptic potentials. Nicotine-evoked [Ca(2+)](i) peaks were reduced by conotoxin and blocked by ruthenium red or tetrodotoxin. Fast [Ca(2+)](i) imaging can be used to directly record single action potentials in enteric neurones. [Ca(2+)](i) peaks required opening of voltage-gated sodium and calcium channels as well as Ca(2+) release from intracellular stores. PMID- 22041185 TI - Serine racemase deletion abolishes light-evoked NMDA receptor currents in retinal ganglion cells. AB - Glycine and/or D-serine are obligatory coagonists of the N-methyl-D-aspartate receptor (NMDAR). Serine racemase, the D-serine-synthesizing enzyme, is expressed by astrocytes and Muller cells of the retina, but little is known about its role in retinal signalling. In this study, we utilize a serine racemase knockout (SRKO) mouse to explore the contribution of D-serine to inner-retinal function. Retinal tissue levels of D-serine in SRKO mice are reduced by 85%. Whole-cell recordings from SRKO retinal ganglion cells showed markedly reduced coagonist occupancy of NMDARs and consequently a dramatic reduction in the NMDAR component of light-evoked responses. NMDAR currents in SRKOs could be rescued by applying exogenous coagonist, but SRKO ganglion cells still displayed lower NMDA/AMPA receptor ratios than wild-type (WT) controls when the coagonist site was saturated. Despite having abnormalities in synaptic glutamatergic transmission, SRKO mice displayed no obvious signs of visual impairment in behavioural testing. These findings raise interesting questions about the role of D-serine in inner retinal function and development. PMID- 22041186 TI - Differential effects of Kv7 (M-) channels on synaptic integration in distinct subcellular compartments of rat hippocampal pyramidal neurons. AB - The K(V)7/M-current is an important determinant of neuronal excitability and plays a critical role in modulating action potential firing. In this study, using a combination of electrophysiology and computational modelling, we show that these channels selectively influence peri-somatic but not dendritic post-synaptic excitatory synaptic potential (EPSP) integration in CA1 pyramidal cells. K(V)7/M channels are highly concentrated in axons. However, the competing peptide, ankyrin G binding peptide (ABP) that disrupts axonal K(V)7/M-channel function, had little effect on somatic EPSP integration, suggesting that this effect was due to local somatic channels only. This interpretation was confirmed using computer simulations. Further, in accordance with the biophysical properties of the K(V)7/M-current, the effect of somatic K(V)7/M-channels on synaptic potential summation was dependent upon the neuronal membrane potential. Somatic K(V)7/M channels thus affect EPSP-spike coupling by altering EPSP integration. Interestingly, disruption of axonal channels enhanced EPSP-spike coupling by lowering the action potential threshold. Hence, somatic and axonal K(V)7/M channels influence EPSP-spike coupling via different mechanisms. This may be important for their relative contributions to physiological processes such as synaptic plasticity as well as patho-physiological conditions such as epilepsy. PMID- 22041187 TI - Characterization of Trpm1 desensitization in ON bipolar cells and its role in downstream signalling. AB - ON bipolar cells invert the sign of light responses from hyperpolarizing to depolarizing before passing them on to ganglion cells. Light responses are generated when a cation channel, recently identified as Trpm1, opens. The amplitude of the light response rapidly decays due to desensitization of Trpm1 current. The role of Trpm1 desensitization in shaping light responses both in bipolar and downstream ganglion cells has not been well characterized. Here we show that two parameters, the amount and the rate of recovery from desensitization, depend on the strength of the presynaptic stimulus. Stimuli that activate less than 20% of the maximum Trpm1 current did not promote any detectable desensitization, even for prolonged periods. Beyond this threshold there was a linear relationship between the amount of desensitization and the fractional Trpm1 current. In response to stimuli that open all available channels, desensitization reduced the response to approximately 40% of the peak, with a time constant of 1 s, and recovery was slow, with a time constant of more than 20 s. In dye-filled bipolar cells classified as transient or sustained using morphological criteria, there were no significant differences in Trpm1 desensitization parameters. Trpm1 activation evoked robust EPSCs in ganglion cells, and removal of Trpm1 desensitization strongly augmented a sustained component of the ganglion cell EPSC irrespective of whether ganglion cells were of the ON or ON/OFF type. We conclude that Trpm1 desensitization impacts the kinetics of ganglion cell EPSCs, but does not underlie the sustained/transient dichotomy of neurons in the ON pathway. PMID- 22041189 TI - Skin sympathetic nerve activity component synchronizing with cardiac cycle is involved in hypovolaemic suppression of cutaneous vasodilatation in hyperthermia. AB - Although cutaneous vasodilatation in hyperthermia was suppressed during hypovolaemia, the efferent neural pathway mediating this suppression has not been identified. To determine the electrical nerve signals which account for the suppression of cutaneous vasodilatation during hypovolaemia, skin sympathetic nerve activity (SSNA; microneurography) from the peroneal nerve, laser-Doppler blood flow (LDF) on the ipsilateral dorsal foot, mean arterial pressure (MAP; sonometry) and oesophageal temperature (T(oes)) were measured before and during 45 min of passive warming in 20 healthy subjects during normovolaemia (n = 10) or hypovolaemia (n = 10) conditions. Hypovolaemia was achieved by diuretic administration. Cutaneous vascular conductance (CVC = LDF/MAP), SSNA burst frequency and total SSNA obtained from rectified and filtered SSNA signal increased as T(oes) increased by ~0.5 degrees C by the end of warming in both groups. The increase in CVC was significantly lower in hypovolaemia than normovolaemia (P < 0.0001), but with no significant difference in the increase in burst frequency and total SSNA between groups (P > 0.32). However, using an alternative analysis that constructed spike incidence histograms from the original signal using 0.05 s bins during the 5 s following a given R-wave, we found a SSNA component synchronized with the cardiac cycle with a 1.1-1.3 s latency. This component increased with an increase in T(oes) and the increase was significantly suppressed by hypovolaemia (P < 0.0001). In conclusion, hypovolaemic suppression of cutaneous vasodilatation during hyperthermia might be caused by a reduction in the SSNA component synchronized with cardiac cycle. PMID- 22041188 TI - Orai3--the 'exceptional' Orai? AB - The field of agonist-activated Ca(2+) entry in non-excitable cells underwent a revolution some 5 years ago with the discovery of the Orai proteins as the essential pore-forming components of the low-conductance, highly Ca(2+)-selective CRAC channels whose activation is dependent on depletion of intracellular stores. Mammals possess three distinct Orai proteins (Orai1, 2 and 3) of which Orai3 is unique to this class, apparently evolving from Orai1. However, the sequence of Orai3 shows marked differences from that of Orai1, particularly in those regions of the protein outside of the essential pore-forming domains. Correspondingly, studies from several different groups have indicated that the inclusion of Orai3 is associated with the appearance of conductances that display unique features in their gating, selectivity, regulation and mode of activation. In this Topical Review, these features are discussed with the purpose of proposing that the evolutionary appearance of Orai3 in mammals, and the consequent development of conductances displaying novel properties - whether formed by Orai3 alone or in conjunction with the other Orai proteins - is associated with the specific role of this member of the Orai family in a unique range of distinct cellular activities. PMID- 22041190 TI - MicroRNAs in vascular biology, an introduction to the Vascular Pharmacology special issue on microRNAs. PMID- 22041192 TI - Thrombolysis for massive pulmonary embolism in pregnancy: a case report. AB - Mortality from pulmonary embolism (PE) in pregnancy might be related to challenges in targeting the right population for prevention. Such targeting could help ensure that the correct diagnosis is suspected and adequately investigated, and allow the initiation of the timely and best possible treatment of this disease. In the literature to date only 18 case reports of thrombolysis in pregnant women with PE have been reported, and showed beneficial effects for both mother and fetus in terms of mortality and complications with acceptable bleeding risks. We present here the case of a pregnant patient with massive PE who underwent successful thrombolysis. A 26-year-old pregnant (at 24 weeks) woman was admitted 4 h after onset of sudden acute dyspnea and chest pain. An immediate electrocardiogram showed a typical S1-Q3-T3 pattern. The echocardiogram showed a distended right ventricle with free-wall hypokinesia and displacement of the interventricular septum toward the left ventricle. Thrombolysis with recombinant tissue plasminogen activator (alteplase 10 mg bolus, then 90 mg over 2 h) was administered. Pelvic examination and ultrasound showed regular fetal heart beat, and regular placental and liquid presence. No problems developed for the mother or fetus in the subsequent days or at discharge. In conclusion, in pregnant patients with life-threatening massive PE, thrombolytic therapy can be administered, and the use of echocardiographic, laboratory, and clinical data can be useful tools to achieve a rapid diagnosis and make a therapeutic decision, but additional studies need to be performed to further define its use. PMID- 22041191 TI - A multi-tissue type genome-scale metabolic network for analysis of whole-body systems physiology. AB - BACKGROUND: Genome-scale metabolic reconstructions provide a biologically meaningful mechanistic basis for the genotype-phenotype relationship. The global human metabolic network, termed Recon 1, has recently been reconstructed allowing the systems analysis of human metabolic physiology and pathology. Utilizing high throughput data, Recon 1 has recently been tailored to different cells and tissues, including the liver, kidney, brain, and alveolar macrophage. These models have shown utility in the study of systems medicine. However, no integrated analysis between human tissues has been done. RESULTS: To describe tissue-specific functions, Recon 1 was tailored to describe metabolism in three human cells: adipocytes, hepatocytes, and myocytes. These cell-specific networks were manually curated and validated based on known cellular metabolic functions. To study intercellular interactions, a novel multi-tissue type modeling approach was developed to integrate the metabolic functions for the three cell types, and subsequently used to simulate known integrated metabolic cycles. In addition, the multi-tissue model was used to study diabetes: a pathology with systemic properties. High-throughput data was integrated with the network to determine differential metabolic activity between obese and type II obese gastric bypass patients in a whole-body context. CONCLUSION: The multi-tissue type modeling approach presented provides a platform to study integrated metabolic states. As more cell and tissue-specific models are released, it is critical to develop a framework in which to study their interdependencies. PMID- 22041193 TI - Synthesis and characterization of Mn doped ZnS d-dots with controllable dual color emissions. AB - High-quality Mn doped ZnS d-dots were successfully synthesized via an alternative route based on the solvothermal method using oleic acid as stabilizing agent. X ray diffraction (XRD), transmission electron microscopy (TEM) as well as photoluminescence (PL) spectra were employed to characterize the obtained samples. The as-obtained d-dots are highly crystalline and uniform sized, and they can be well dispersed in hexane to form stable and clear colloidal solution. The optical properties of the d-dots with different Mn doped concentration are investigated in detail. The Mn doped ZnS d-dots have two emission bands, including surface state emission (blue) and Mn emission (orange), which are both sensitivity to the Mn doped concentration. By varying the Mn doped concentration, the relative PL intensities of dual-color emissions can be well manipulated, showing their application in tunable color output. Furthermore, a subsequent ligand exchange has been introduced to give the d-dots hydrophilic surfaces, which are favorable for biological applications. PMID- 22041194 TI - Binary mixtures with novel monomeric and dimeric surfactants: influence of the head group nature and number of hydrophobic chains on non-ideality. AB - The micellization and micellar growth in the mixtures of N,N-dimethyl, N-phenyl,N dodecylammonium bromide, PH12, N,N-dimethyl,N-ciclohexylmethyl,N-dodecylammonium bromide, CH12, and their two dimeric counterparts m-dimethylphenyl-alpha-omega bis(dodecyldimethylammonium) bromide, 12PH12, and m-dimethylciclohexyl-alpha omega-bis(dodecyldimethylammonium) bromide, 12CH12, with dodecyltrimethylammoniumbromide, DTAB, and with N-decanoyl N-methylglucamide, MEGA10, were investigated at 303 K. Circular dichroism, CD, experiments showed the formation of mixed micelles. Two-dimensional, 2D, rotating frame nuclear Overhauser effect spectroscopy (ROESY) experiments indicated that the arrangement of the rings in the pure and mixed micelles is similar, with the rings bent into the micelle interior avoiding contact with water. Application of different theoretical approaches shows that PH12 and CH12 mixtures with DTAB and with MEGA10 behave almost ideally. The binary systems of 12PH12 and 12CH12 with DTAB and with MEGA10 show a non-ideal behavior. An increment in the solution mole fraction of MEGA10 and DTAB diminishes the tendency of the micellar aggregates to grow. PMID- 22041195 TI - Selective surface reactions for Janus ORMOSIL particles with multiple functional groups using an ordered monolayer film at liquid-liquid interface. AB - Monodispersed, submicron-sized Janus ORMOSIL particles with multiple functional groups were prepared by the selective surface reaction of a monolayer film formed at a hexane-water interface. A well-ordered monolayer film was obtained by self assembly of ORMOSIL particles with multiple functional groups at hexane-water interface. The photopolymerization of an ordered monolayer containing ORMOSIL particles yields a rigid film strong enough to maintain its integrity for transfer and further chemical reaction. The chemical reaction of this ordered film with organic and inorganic functional groups produced Janus ORMOSIL particles with multiple functional groups. The morphologies, structures, and chemical compositions of monolayer films and Janus ORMOSIL particles were characterized by FT-IR, solid state NMR, X-ray diffraction (XRD), optical microscopy (OM), electron microscopies (SEM and TEM), and confocal laser scanning microscopy. PMID- 22041196 TI - Effect of cosolvent organic molecules on the adsorption and structural properties of soft-templated ordered mesoporous alumina. AB - Ordered mesoporous aluminas with high surface areas (up to 783 m(2)/g), large pore volumes (up to 0.82 cm(3)/g) and the presence of complementary micropores (up to 0.17 cm(3)/g) are synthesized with Pluronic(r) F127 or P123 triblock copolymers in a one-pot synthesis of metal alkoxide, template and cosolvent molecules such as 1,3,5-trimethylbenzene or 1,3,5-triisopropylbenzene in an acidic ethanol solution at 15 degrees C. Materials are characterized by nitrogen adsorption analysis, small-angle X-ray diffraction and transmission electron microscopy. PMID- 22041197 TI - Water adsorption-desorption isotherms of two-dimensional hexagonal mesoporous silica around freezing point. AB - Zr-doped mesoporous silica with a diameter of approximately 3.8 nm was synthesized via an evaporation-induced self-assembly process, and the adsorption desorption isotherms of water vapor were measured in the temperature range of 263 298 K. The measured adsorption-desorption isotherms below 273 K indicated that water confined in the mesopores did not freeze at any relative pressure. All isotherms had a steep curve, resulting from capillary condensation/evaporation, and a pronounced hysteresis. The hysteresis loop, which is associated with a delayed adsorption process, increased with a decrease in temperature. Furthermore, the curvature radius where capillary evaporation/condensation occurs was evaluated by the combined Kelvin and Gibbs-Tolman-Koening-Buff (GTKB) equations for the modification of the interfacial tension due to the interfacial curvature. The thickness of the water adsorption layer for capillary condensation was slightly larger, whereas that for capillary evaporation was slightly smaller than 0.7 nm. PMID- 22041198 TI - Influence of temperature on the colloidal stability of the F-DPPC and DPPC liposomes induced by lanthanum ions. AB - The influence of La(3+) on the colloidal stability of liposomes made up by two zwitterionic phospholipids, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-[16-fluoropalmitoyl-phosphatidylcholine (F-DPPC), in aqueous media has been investigated by dynamic light scattering and electrophoretic mobility. The critical aggregation concentration (c.a.c.) of La(3+) for F-DPPC and DPPC liposomes were experimentally obtained, and the results were compared with theoretical predictions using the Derjaguin-Landau-Verwey-Overbeek theory. In order to evaluate the influence of the state of the bilayer on the stability of liposomes, all experiments were performed at temperatures below and above the chain-melting phase-transition temperature of lipids (transition temperature of lipids). Changes in the size of both types of liposomes and high values of polydispersity in the presence of La(3+) showed that these ions induce aggregation of liposomes at 25 degrees C and at 60 degrees C. At 25 degrees C, when the bilayer of F-DPPC liposomes is interdigited, DPPC liposomes are more resistant to aggregation than the liposomes formed with F-DPPC. However, this difference disappears at 60 degrees C, when both bilayers have the same conformation. The experimental results also indicate that the c.a.c. is higher at 60 degrees C than at 25 degrees C for both types of liposomes. In fact, it has been observed by dynamic light scattering measurements that aggregation of liposomes at 25 degrees C can be prevented by increasing the solution temperature for La(3+) concentrations near to the c.a.c. Moreover, the behavior of these liposomes in the presence of the ion was studied at temperatures above and below the transition temperature of the phospholipids. PMID- 22041199 TI - Self-assembly in surfactant-based liquid mixtures: octanoic acid/Bis(2 ethylhexyl)amine systems. AB - The physico-chemical properties of Bis(2-ethylhexyl)amine (BEEA) plus octanoic acid (OA) mixtures have been investigated by IR, SAXS, WAXS, viscosimetry, and AC complex impedance spectroscopy in the whole composition range. Mainly driven by proton transfer from the acidic OA to the basic BEEA, the formation of stoichiometrically well-defined adducts takes place in the mixtures. This causes the slowing down of molecular dynamics and the increase in charge carrier number density. Interestingly, while the pure components possess no significant conductivity (about 10(-12) S cm(-1) at 25 degrees C), their mixtures show a composition-dependent enhanced conductivity (up to about 10(-5) S cm(-1)), i.e., more than seven orders of magnitude higher than that of the pure components. The comparison of the composition dependence of viscosity, direct-current conductivity, and static permittivity indicates the concurrence of contributions of different adducts and that the dynamics controlling molecular reorientation and momentum and charge transfer, even if ultimately related to the proton transfer from OA to BEEA, are different. The results can be used not only to design novel materials for application purposes, but also to shed more light on the principles regulating molecular self-assembly in surfactant-based liquid systems. PMID- 22041200 TI - Wafer-scale thin encapsulated two-dimensional nanochannels and its application toward visualization of single molecules. AB - We present a new and simple approach to fabricate wafer-scale, thin encapsulated, two-dimensional nanochannels by using conventional surface-micromachining technology and thin-film evaporation. The key steps to the realization of two dimensional nanochannels are a fine etching of a sacrificial layer to create underetching spaces at the nanometer regime, and an accurate thin-film evaporation for encapsulation. Well-defined cross-sectional, encapsulated nanochannel arrays with dimensions as small as 20 nm in both width and height have been realized at the wafer-scale. The fabricated nanochannels with a channel length of 10mm have been used as a suitable fluidic platform for confining a solution containing nanomolar concentrations of Alexa fluorescent molecules. Initial results toward visualization of single Alexa molecules in the confined solution are reported. PMID- 22041201 TI - Genome sequence of SeIV-1, a novel virus from the Iflaviridae family infective to Spodoptera exigua. AB - Analysis of the transcriptome of Spodoptera exigua larvae revealed the presence of several ESTs with homology to virus of the order Picornavirales and with the highest similarity to Infectious flacherie virus (Iflaviridae) that infects Bombyx mori larvae. Iflaviridae is a recently defined family of insect-infecting viruses that consist of positive single strand RNA genomes translated into a single polyprotein of around 3000 amino acids long. Using the sequence information derived from the obtained ESTs, we have completed the genomic sequence of this virus. The novel S. exigua iflavirus (SeIV-1) has a genome of 10.3 kb and codes for a 3222 aa polyprotein. Expression analysis has revealed the presence of the virus in all tissues tested and insect stages, being more abundant in the midgut of the larvae. High infectivity of this virus against S. exigua has been demonstrated after observing the presence of this virus in different colonies that were reared in the same chamber with the virus-infected colony, despite no evidence of pathological effects. Further study of viral covert infections of SeIV-1 could lead to a better understanding of its pathological effect as well as any possible interaction with other microbial pathogens used for the control of this pest. PMID- 22041202 TI - Analysis of a naturally-occurring deletion mutant of Spodoptera frugiperda multiple nucleopolyhedrovirus reveals sf58 as a new per os infectivity factor of lepidopteran-infecting baculoviruses. AB - The Nicaraguan population of Spodoptera frugiperda multiple nucleopolyhedrovirus, SfMNPV-NIC, is structured as a mixture of nine genotypes (A-I). Occlusion bodies (OBs) of SfMNPV-C, -D and -G pure genotypes are incapable of oral transmission; a phenotype which in SfMNPV-C and -D is due to the absence of pif1 and pif2 genes. The complete sequence of the SfMNPV-G genome was determined to identify possible factors involved in this phenotype. Deletions of 4860 bp (22,366-27,225) and 60 bp (119,759-119,818) were observed in SfMNPV-G genome compared with that of the predominant complete genotype SfMNPV-B (132,954 bp). However no genes homologous to previously described per os infectivity factors were located within the deleted sequences. Significant differences were detected in the nucleotide sequence in sf58 gene (unknown function) that produced changes in the amino acid sequence and the predicted secondary structure of the corresponding protein. This gene is conserved only in lepidopteran baculoviruses (alpha- and betabaculoviruses). To determine the role of sf58 in peroral infectivity a deletion mutant was constructed using bacmid technology. OBs of the deletion mutant (Sf58null) were not orally infectious for S. frugiperda larvae, whereas Sf58null rescue virus OBs recovered oral infectivity. Sf58null DNA and occlusion derived virions (ODVs) were as infective as SfMNPV bacmid DNA and ODVs in intrahemocelically infected larvae or cell culture, indicating that defects in ODV or OB morphogenesis were not involved in the loss of peroral infectivity. Addition of optical brightener or the presence of the orally infectious SfMNPV-B OBs in mixtures with SfMNPV-G OBs did not recover Sf58null OB infectivity. According to these results sf58 is a new per os infectivity factor present only in lepidopteran baculoviruses. PMID- 22041203 TI - Oral toxicity of Photorhabdus culture media on gene expression of the adult sweetpotato whitefly, Bemisia tabaci. AB - The oral toxicity of culture media of the symbiotic bacteria, Photorhabdus temperata, mutually associated with entomopathogenic nematode Heterorhabditis megidis and Photorhabdus luminescens ssp. laumondii (TT01) mutually associated with Heterorhabditis bacteriophora, were investigated in the adults of Bemisia tabaci. The oral ingestion of sucrose diet solutions (20%) containing bacteria free supernatant of the culture media from symbiotic bacteria gradually increased mortalities and was completely lethal at 60 h after the treatments, whereas the mortalities of the controls, sucrose solutions with or without media that uncultured with bacteria, were less than 17% up to 84 h of incubation. The effects of oral ingestion of symbiont culture media were demonstrated on the expression rates of several genes of B. tabaci using quantitative real-time RT PCR analysis. Genes associated with immunity (knottin) and nervous system (acetylcholine receptor, acetylcholine esterase and sodium channel) were up regulated while genes involved in metabolism (cytochromep450 and carboxylesterase) were down-regulated, but genes involved in development (ecdysone receptor), reproduction (vitellogenin) and stress (hsp70, hsp90 and shsp) did not change transcription rates. Our results provide information for the understanding of the mechanism of symbiont pathogenic factors for the manipulation of host physiology at the transcription level. PMID- 22041204 TI - Canine distemper spillover in domestic dogs from urban wildlife. AB - Canine distemper virus (CDV) causes a major disease of domestic dogs that develops as a serious systemic infection in unvaccinated or improperly vaccinated dogs. Domesticated dogs are the main reservoir of CDV, a multihost pathogen. This virus of the genus Morbillivirus in the family Paramyxoviridae occurs in other carnivorous species including all members of the Canidae and Mustelidae families and in some members of the Procyonidae, Hyaenidae, Ursidae, and Viverridae families. Canine distemper also has been reported in the Felidae family and marine mammals. The spread and incidences of CDV epidemics in dogs and wildlife here and worldwide are increasing. PMID- 22041205 TI - Astroviruses in dogs. AB - Canine astroviruses appear to be widespread geographically. The prevalence may be significantly higher in pups with gastroenteric disease than in asymptomatic animals and virus shedding has been shown to correlate with gastroenteric signs in naturally infected dogs. Animal experiments are required to understand better the pathogenic role of astroviruses in dogs. PMID- 22041206 TI - Canine reproductive, respiratory, and ocular diseases due to canine herpesvirus. AB - This review documents how clinical inquiry expands as our knowledge base about canine herpesvirus (CHV) increases. We must understand the various forms of CHV infection that may occur in the dog population. This has prompted the veterinary community to develop more sensitive diagnostic assays. CHV is more common than we considered a decade ago. Up to 70% of some high-risk dog populations have been infected with and are latent carriers of CHV. Recognition of the various forms of CHV-induced disease, availability of diagnostic assays with increased sensitivity, and the formation of reliable biosecurity measures will allow for better control steps. PMID- 22041207 TI - Canine coronavirus: not only an enteric pathogen. AB - This article reviews the currently available literature on pantropic canine coronavirus (CCoV), providing a meaningful update on the virologic, epidemiologic, clinical, diagnostic, and prophylactic aspects of the infections caused by this emerging pathogen of dogs. It also describes pantropic CCoV induced disease reproduced under experimental conditions. PMID- 22041208 TI - Feline coronavirus in multicat environments. AB - Feline infectious peritonitis (FIP), a fatal disease in cats worldwide, is caused by FCoV infection, which commonly occurs in multicat environments. The enteric FCoV, referred to as feline enteric virus (FECV), is considered a mostly benign biotype infecting the gut, whereas the FIP virus biotype is considered the highly pathogenic etiologic agent for FIP. Current laboratory tests are unable to distinguish between virus biotypes of FCoV. FECV is highly contagious and easily spreads in multicat environments; therefore, the challenges to animal shelters are tremendous. This review summarizes interdisciplinary current knowledge in regard to virology, immunology, pathology, diagnostics, and treatment options in the context of multicat environments. PMID- 22041209 TI - Canine noroviruses. AB - Noroviruses are recognized as emerging enteric pathogens of humans and have been identified in recent years in a number of mammalian species. The role of noroviruses as pathogens in immune-competent animals and under natural conditions remains uncertain, although both homologous and heterologous animal models are now available to investigate the pathogenesis, the immune response, and the molecular mechanism regulating norovirus infection. Recently, evidence has been gathered that noroviruses may also circulate in domestic carnivores. The zoonotic implications of these novel viruses deserve more attention, due to the strict social interactions between humans and pets. PMID- 22041210 TI - Canine papillomaviruses. AB - Papillomaviruses can infect epithelia and induce proliferative disorders. Different types of canine papillomaviruses have been found to be associated with distinct pathologies including exophytic warts as in canine oral papillomatosis, endophytic warts, and pigmented plaques and, in some cases, squamous cell carcinomas. Virus infection is followed by a phase of subclinical infection before the onset of symptoms. A diagnosis can in some cases be made clinically but should be verified if there are any doubts. Most papillomas do regress spontaneously within a few months. Preventative vaccination is possible but not on the market. PMID- 22041211 TI - Feline immunodeficiency virus: disease association versus causation in domestic and nondomestic felids. AB - Feline immunodeficiency virus (FIV) is an important infection in both domestic and nondomestic cats. Although many studies have provided insight into FIV pathophysiology and immunologic responses to infection in cats, questions remain regarding the association of FIV with specific disease syndromes. For many diseases, both association and causation of disease with FIV remain to be confirmed and clarified. The use of experimental infection models is unlikely to yield answers about naturally infected domestic cats and is not feasible in nondomestic felids, many of which are endangered species. Researches might consider further study of naturally occurring disease with an emphasis on confirming which diseases have a likely association with FIV. PMID- 22041212 TI - Canine brucellosis management. AB - Infertility in dogs is a growing concern in breeding kennels. There are a number of bacteria, viruses, and husbandry practices that must be considered to determine the cause of decreased litter sizes, abortions, weak puppies, and lack of pregnancy, but brucellosis should be at the top of the differential list. PMID- 22041213 TI - Hepatozoon spp infections in the United States. AB - Two Hepatozoon spp are recognized as parasites of domestic dogs in the United States, H. canis and H. americanum. H. canis was first described in India in 1905 and has been documented in many areas of the world, although not definitively identified in North America until recently. H. americanum, causing American canine hepatozoonosis, was first documented in a coyote in 1978 and is now considered an emerging etiologic agent of disease in domestic dogs throughout the United States. The authors review current knowledge of canine hepatozoonosis caused by H. canis and H. americanum and elaborate on more recent research findings. PMID- 22041214 TI - North American snake envenomation in the dog and cat. AB - Snake envenomation can be a cause of significant morbidity in dogs and cats in North America. Being familiar with the venomous snakes in your area and understanding the mechanisms of action of their venom will allow for successful treatment of envenomation cases. Treatment of snake envenomation revolves around supportive care in mild to moderate cases and venom neutralization with antivenom in severe cases. Dogs and cats envenomated by North American snakes have a good prognosis if treated appropriately. PMID- 22041215 TI - Disease transmission from companion parrots to dogs and cats: what is the real risk? AB - A number of common misconceptions exist regarding the degree of transmission from companion parrots to dogs and cats. Concern regarding bacterial, viral, fungal, and parasitic transmission is generally unfounded, because disease transmission between companion parrots and dogs and cats is not well-documented. Infections with Mycobacterium spp, Aspergillus spp, Giardia spp, Chlamydophila psittaci, Salmonella spp, Yersinia pseudotuberculosis, Cryptococcus neoformans, Histoplasma capsulatum, Cryptosporidium spp, and avian influenza are often considered possible transmissible diseases, causing pet caregivers unwarranted concerns. PMID- 22041216 TI - Feline respiratory disease complex. AB - Feline respiratory disease complex (FRDC) refers to the characteristic acute presentation of a contagious respiratory or ocular disease caused by one or multiple pathogens. Environmental and host factors impact the transmission, clinical presentation, preventive strategy, and treatment of affected cats. The FRDC is especially problematic in settings where large numbers of cats cohabit, including animal shelters, catteries, and semi-feral colonies. Although elimination of FRDC is an unrealistic goal, improved understanding can lead to strategies to minimize disease impact. PMID- 22041218 TI - Location and progression of white-matter lesions, lacunar infarcts and atrophy associated with motivational and mood symptoms in patients with symptomatic atherosclerotic disease: things to ponder. PMID- 22041220 TI - Limited Rank Matrix Learning, discriminative dimension reduction and visualization. AB - We present an extension of the recently introduced Generalized Matrix Learning Vector Quantization algorithm. In the original scheme, adaptive square matrices of relevance factors parameterize a discriminative distance measure. We extend the scheme to matrices of limited rank corresponding to low-dimensional representations of the data. This allows to incorporate prior knowledge of the intrinsic dimension and to reduce the number of adaptive parameters efficiently. In particular, for very large dimensional data, the limitation of the rank can reduce computation time and memory requirements significantly. Furthermore, two- or three-dimensional representations constitute an efficient visualization method for labeled data sets. The identification of a suitable projection is not treated as a pre-processing step but as an integral part of the supervised training. Several real world data sets serve as an illustration and demonstrate the usefulness of the suggested method. PMID- 22041221 TI - The use of sudafed for priapism in pediatric patients with sickle cell disease. PMID- 22041222 TI - Perioperative management of obstructive sleep apnea: a survey of Veterans Affairs health care providers. AB - OBJECTIVES/HYPOTHESIS: (1) To determine the presence of Veterans Affairs (VA) institutional guidelines for the perioperative management of obstructive sleep apnea (OSA); (2) to examine current use of preoperative screening tools for OSA in the VA; and (3) to understand current VA practice patterns regarding postoperative disposition of patients with OSA. STUDY DESIGN: Survey study. SETTING: Veterans Affairs hospitals with surgical services; sample size 102 facilities. SUBJECTS: Veterans Affairs health care providers. METHODS: The authors surveyed health care providers at VA hospitals using a survey tool developed by the authors. RESULTS: The response rate was 80%. A variety of preoperative screening tools for OSA were used by respondents, most commonly American Society of Anesthesiologists guidelines (53%). A policy for postoperative disposition of known and presumed OSA was present in 26% and 19% of responses, respectively. Of those respondents reporting a formal postoperative care policy, 48% and 30% admitted patients to a monitored ward bed and surgical intensive care unit, respectively. Of the 74% of respondents unaware of an institutional policy, Anesthesia and Surgery worked together to dictate postoperative disposition of patients with known OSA 73% of the time. The degree of OSA was ranked as the most important factor (58%) influencing postoperative disposition. Ten percent of respondents reported a major perioperative complication attributable to OSA in the past year. CONCLUSION: This survey study elucidates the heterogeneity of preoperative screening for and postoperative care of veterans with OSA. Future investigators may use these data to formalize institutional policies with regard to patients with OSA, with potentially significant impacts on patient care and usage of financial resources. PMID- 22041223 TI - Inhibition of alpha folate receptor resulting in a reversal of taxol resistance in nasopharyngeal carcinoma. AB - OBJECTIVE: To further determine the role of FOLR1 in taxol resistance of nasopharyngeal carcinoma (NPC) and whether inhibition of FOLR1 expression reverses the taxol-resistant phenotype. STUDY DESIGN: Correlation study between gene expression and cancer cell survival. SETTING: University hospital. SUBJECTS AND METHODS: Three taxol-resistant sub-cell lines with a different resistant index were established from the parental CNE-1 NPC cell line. The correlation between FOLR1 expression and taxol sensitivity was statistically analyzed. Inhibition of FOLR1 expression was carried out by RNA interference and by a FOLR1 specific monoclonal antibody, and taxol sensitivity was examined by colony formation assays. FOLR1 expression was also examined in 72 NPC patient specimens by immunohistochemistry. RESULTS: The levels of FOLR1 expression were positively and significantly correlated with a taxol resistance phenotype (P < .05). Inhibition of FOLR1 expression resulted in a significantly increased sensitivity of taxol to taxol-resistant NPC cells (P < .05). An increase of FOLR1 expression by gene transfection caused a taxol-resistant phenotype in parental NPC cells. The level of FOLR1 expression was found to be related to clinical stage in NPC tissue samples. CONCLUSION: These results suggest that FOLR1 plays an important role in taxol resistance of NPC cells. PMID- 22041224 TI - A closed-loop stimulation system supplemented with motoneurone dynamic sensitivity replicates natural eye blinks. AB - OBJECTIVE: The authors are designing an implantable device that will electrically stimulate a paretic eyelid when electrodes implanted into the contralateral healthy orbicularis oculi muscle detect a spontaneous blink activity. As a novelty, the stimulation pattern includes the dynamic sensitivity of motor units, thus obtaining complete eyelid closure, tailored on the kinematics of the natural eye blink. STUDY DESIGN: A preliminary study was performed on 10 healthy subjects, to observe, first, the kinematics of their natural eye blink and, second, the eye blink stimulated by a dynamic vs nondynamic pattern. SETTING: A microaccelerometer taped onto the left upper eyelid detected its kinematics. A dedicated LabView software built up and triggered the stimulation pattern. A webcam recorded the behavioral effect. SUBJECTS AND METHODS: The kinematics of spontaneous eye blinks was detected. Then, an epicutaneous stimulation of the facial nerve branch for the left orbicularis oculi muscle was performed on the same subjects. Muscle recruitment curves were studied, and acceleration of the bionic blink was measured and compared with the natural one. RESULTS: Kinematics of the natural eyelid is highly variable within subjects. The stimulation pattern frequency was set case by case in order to obtain the desired eyelid acceleration of the contralateral eye. A custom-fit dynamic stimulation leads to a symmetrical natural-like eye blink. CONCLUSIONS: By adding the dynamic pulse, the authors were able to tailor a bionic eye blink, which was hardly distinguishable from the subject's natural one. PMID- 22041225 TI - The control of chromosome segregation during mitosis in epithelial cells by substrate elasticity. AB - Materials of defined elasticity, including synthetic material scaffolds and tissue-derived matrices, can regulate biological responses of cells and in particular adhesion, migration, growth and differentiation which are essential parameters for tissue integration. These responses have been extensively investigated in interphase cells, but little is known whether and how material elasticity affects mitotic cells. We used polyelectrolyte multilayer films as model substrates with elastic modulus ranging from Eap = 0 up to Eap = 500 kPa and mitotic PtK2 epithelial cells to address these important questions. Soft substrates (Eap < 50 kPa) led to abnormal morphology in chromosome segregation, materialized by chromatin bridges and chromosome lagging. Frequency of these damages increased with decreasing substrate stiffness and was correlated with a pro-apoptotic phenotype. Mitotic spindle was not observed on soft substrates where formation of chromatin damages is due to low beta1-integrin engagement and decrease of Rac1 activities. This work constitutes the first evidence that soft substrates hinder epithelial cell division. In perspective, our findings emphasize the prime incidence of the material elasticity on the fate of the phenotype, especially of stem cells in the mitotic phase. PMID- 22041226 TI - The ventrolateral preoptic nucleus is not required for isoflurane general anesthesia. AB - Neurons of the ventrolateral preoptic nucleus (VLPO) promote sleep and VLPO loss produces insomnia. Previous studies show that general anesthetics including isoflurane activate VLPO neurons, and may contribute to their sedative effects. However, it is not clear to what extent the activation of VLPO neurons contributes to general anesthesia. We tested whether destruction of the VLPO neurons would affect the onset, depth, or recovery from isoflurane's general anesthetic effects. The VLPO was ablated in 25 rats by bilateral local injection of orexin-saporin, and polysomnography was performed to measure baseline sleep loss and responses to isoflurane anesthesia at 1% and 2%. Eight rats received sham (saline) injections. We measured isoflurane effects on time to loss of righting reflex, onset of continuous slow wave activity, and burst suppression; burst-suppression ratio; and time to recovery of righting reflex and desynchronized EEG. VLPO neuron cell loss was quantified by post hoc histology. Loss of VLPO neurons as well as lesion size were associated with cumulative sleep loss (r=0.77 and r=0.62, respectively), and cumulative sleep loss was the strongest predictor of high sensitivity to anesthesia, expressed as decreased time to loss of righting reflex (-0.59), increased burst-suppression ratio (r=0.52) , and increased emergence time (r=0.54); an interaction-effect of isoflurane dose was observed (burst-suppression ratio: p<0.001). We conclude that the sleep loss caused by ablation of VLPO neurons sensitizes animals to the general anesthetic effects of isoflurane, but that the sedation produced by VLPO neurons themselves is not required for isoflurane anesthesia. PMID- 22041227 TI - Modeling fast stimulus-response association learning along the occipito-parieto frontal pathway following rule instructions. AB - On the basis of instructions, humans are able to set up associations between sensory and motor areas of the brain separated by several neuronal relays, within a few seconds. This paper proposes a model of fast learning along the dorsal pathway, from primary visual areas to pre-motor cortex. A new synaptic learning rule is proposed where synaptic efficacies converge rapidly toward a specific value determined by the number of active inputs of a neuron, respecting a principle of resource limitation in terms of total synaptic input efficacy available to a neuron. The efficacies are stable with regards to repeated arrival of spikes in a spike train. This rule reproduces the inverse relationship between initial and final synaptic efficacy observed in long-term potentiation (LTP) experiments. Simulations of learning experiments are conducted in a multilayer network of leaky integrate-and-fire (LIF) spiking neuron models. It is proposed that cortical feedback connections convey a top-down learning-enabling signal that guides bottom-up learning in "hidden" neurons that are not directly exposed to input or output activity. Simulations of repeated presentation of the same stimulus-response pair, show that, under conditions of fast learning with probabilistic synaptic transmission, the networks tend to recruit a new sub network at each presentation to represent the association, rather than re-using a previously trained one. This increasing allocation of neural resources results in progressively shorter execution times, in line with experimentally observed reduction in response time with practice. This article is part of a Special Issue entitled: Neural Coding. PMID- 22041228 TI - Olfactory and respiratory lamina propria transplantation after spinal cord transection in rats: effects on functional recovery and axonal regeneration. AB - Spinal cord injury (SCI) has very poor clinical prospects, resulting in irreversible loss of function below the injury site. Although applied in clinical trials, olfactory ensheathing cells transplantation (OEC) derived from lamina propria (OLP) is still a controversial repair strategy. The present study explored the efficacy of OLP or respiratory lamina propria (RLP) transplantation and the optimum period after SCI for application of this potential therapy. Adult male rats were submitted to spinal cord transection and underwent acute, 2-week or 4-week post-injury transplantation with pieces of OLP (containing OECs) or RLP (without OECs). After grafting, animals with OLP and RLP showed discrete and similar hindlimb motor improvement, with comparable spinal cord tissue sparing and sprouting in the lesion area. Acute transplantation of OLP and RLP seems to foster limited supraspinal axonal regeneration as shown by the presence of neurons stained by retrograde tracing in the brainstem nuclei. A larger number of 5-HT positive fibers were found in the cranial stump of the OLP and RLP groups compared to the lesion and caudal regions. Calcitonin gene-related peptide fibers were present in considerable numbers at the SCI site in both types of transplantation. Our results failed to verify differences between acute, 2-week and 4-week delayed transplantation of OLP and RLP, suggesting that the limited functional and axon reparative effects observed could not be exclusively related to OECs. A greater understanding of the effects of these tissue grafts is necessary to strengthen the rationale for application of this treatment in humans. PMID- 22041229 TI - Serotonin syndrome: take a closer look at the unwell surgical patient. AB - This article describes the sequence of acute clinical deterioration seen in a head and neck oncology patient who developed serotonin syndrome peri-operatively. It highlights the clinical dilemma that can be encountered when a septic picture masks the onset of serotonin syndrome and reinforces the importance of awareness of the potential interactions and side effects associated with drugs that surgeons prescribe. We discuss the pathophysiology, causal factors, clinical presentation and diagnosis of serotonin syndrome as well as highlighting some of the dilemmas that this condition presents in the surgical setting. PMID- 22041230 TI - Sleep apnoea and the surgical list. PMID- 22041231 TI - Current concepts of surveillance and its significance in head and neck cancer. AB - Follow-up in head and neck cancer (hNC) is essential to detect and manage locoregional recurrence or metastases, or second primary tumours at the earliest opportunity. A variety of guidelines and investigations have been published in the literature. This has led to oncologists using different guidelines across the globe. The follow-up protocols may have unnecessary investigations that may cause morbidity or discomfort to the patient and may have significant cost implications. In this evidence-based review we have tried to evaluate and address important issues like the frequency of follow-up visits, clinical and imaging strategies adopted, and biochemical methods used for the purpose. This review summarises strategies for follow-up, imaging modalities and key investigations in the literature published between 1980 and 2009. A set of recommendations is also presented for cost-effective, simple yet efficient surveillance in patients with head and neck cancer. PMID- 22041232 TI - A systematic review of enhanced recovery protocols in colorectal surgery. AB - INTRODUCTION: Colorectal surgery has been associated with a complication rate of 15-20% and mean post-operative inpatient stays of 6-11 days. The principles of enhanced recovery after surgery (ERAS) are well established and have been developed to optimise peri-operative care and facilitate discharge. The purpose of this systematic review is to present an updated review of peri-operative care in colorectal surgery from the available evidence and ERAS group recommendations. METHODS: Systematic searches of the PubMed and EmbaseTM databases and the Cochrane library were conducted. A hand search of bibliographies of identified studies was conducted to identify any additional articles missed by the initial search strategy. RESULTS: A total of 59 relevant studies were identified. These included six randomised controlled trials and seven clinical controlled trials that fulfilled the inclusion criteria. These studies showed reductions in duration of inpatient stays in the ERAS groups compared with more traditional care as well as reductions in morbidity and mortality rates. CONCLUSIONS: Reviewing the data reveals that ERAS protocols have a role in reducing post operative morbidity and result in an accelerated recovery following colorectal surgery. Similarly, both primary and overall hospital stays are reduced significantly. However, the available evidence suggests that ERAS protocols do not reduce hospital readmissions or mortality. These findings help to confirm that ERAS protocols should now be implemented as the standard approach for peri operative care in colorectal surgery. PMID- 22041233 TI - The effect of sterile versus non-sterile tourniquets on microbiological colonisation in lower limb surgery. AB - INTRODUCTION: Surgical tourniquets are commonplace in lower limb surgery. Several studies have shown that tourniquets can be a potential source of microbial contamination but have not compared the use of sterile versus non-sterile tourniquets in the same procedures. METHODS: Patients undergoing elective orthopaedic lower limb surgery were randomised prospectively to use of non sterile pneumatic tourniquet or sterile elastic exsanguination tourniquet (S MARTTM, OHK Medical Devices, haifa, Israel). Samples were taken from the ties of the non-sterile tourniquet prior to surgery and from the sterile tourniquets at the end of the operation in a sterile fashion. These were then sealed in universal containers and immediately analysed by the microbiology department on agar plates, cultured and incubated. RESULTS: Thirty-four non-sterile tourniquets were sampled prior to surgical application, twenty-three of which were contaminated with several different organisms including coagulase-negative Staphylococcus spp, Staphylococcus aureus, Sphingomonas paucimobilis, Bacillus spp, and coliforms. Thirty-six sterile tourniquets were used, with no associated contamination. CONCLUSIONS: There was significant contamination of 68% of orthopaedic surgical tourniquets. These are used regularly in procedures involving the placement of prosthesis and metalwork, and can act as a potential source of infection. We recommend the use of sterile single-use disposable tourniquets where possible. The availability of an alternative should now set the new standard of care and we recommend adopting this as a current NICE guideline for control of surgical site infection. PMID- 22041234 TI - Quality of life after treatment of laryngeal carcinoma: a single centre cross sectional study. AB - INTRODUCTION: Laryngeal cancer treatment inherently affects life's most basic functions and significantly affects quality of life (QOL). We aimed to identify which aspects of QOL and which patients are most affected by the various treatment options. METHODS: The University of Washington Quality of Life (UW QOL) questionnaire was administered to all patients with laryngeal cancer treated at a single institution over a seven-year period (2003-2010). RESULTS: In total, 41 patients responded. All had been treated for squamous cell carcinoma of the larynx. Questionnaires were completed at a median of 18.5 months after treatment. The overall quality of life was 81.1/100 as assessed by the UW-QOL scale, with only 4.9% reporting 'poor' or worse QOL. Neither patient age nor time after treatment significantly affected any aspect of QOL. Patients undergoing primary radiotherapy reported the best QOL. Those undergoing chemoradiotherapy or combined surgical treatment and chemoradiotherapy reported the worst QOL, particularly in terms of social eating, taste and saliva production. Patients with a T stage >=2 and those with nodal metastases reported a significantly worse QOL. CONCLUSIONS: Overall, QOL in our patients was good. This study highlights the aspects of QOL most affected by various treatments for laryngeal cancer and identifies areas in which therapeutic intervention may be focused. It also provides information to guide clinicians when assisting patients to make informed decisions regarding treatment of their head and neck cancer. PMID- 22041235 TI - Classification and management of cervical paragangliomas. AB - INTRODUCTION: Cervical paragangliomas are slow-growing tumours that eventually cause lower cranial nerve palsies and infiltrate the skull base. Surgical treatment may cause the same deficits and, in some, risks more serious neurological deficits. We describe a classification used to guide investigation, consent and management of cervical paragangliomas based on extensive experience. METHODS: The case notes of patients managed by the senior author at a tertiary referral skull base unit between 1987 and 2010 were reviewed retrospectively. A total of 87 cervical paragangliomas were identified in 70 patients (mean age: 46 years, range: 13-77 years). Of these, 35 patients had 36 vagal paragangliomas, 43 patients had 50 carotid body paragangliomas and 8 had both. One cervical paraganglioma arose from neither the carotid body nor the nodose ganglion. The main outcome measures were death, stroke, gastrostomy and tracheotomy. RESULTS: All tumours were classified pre-operatively based on their relationship to the carotid artery, skull base and lower cranial nerves. Type 1 tumours were excised with a transcervical approach, type 2 with a transcervical-parotid approach and type 3 with a combined transcervical-parotid and infratemporal fossa approach. Type 4 patients underwent careful assessment and genetic counselling before any treatment was undertaken. There were no peri-operative deaths; two patients had strokes, one required a long-term feeding gastrostomy and none required a tracheotomy. CONCLUSIONS: The use of a pre-operative classification system guides management and surgical approach, improves accuracy of consent, facilitates audit and clarifies which patients should be referred to specialised centres. PMID- 22041236 TI - Clinical outcome of laparoscopic and open colectomy for right colonic carcinoma. AB - INTRODUCTION: Laparoscopic colorectal surgery has gained widespread acceptance. While many studies have compared laparoscopic and open left-sided resections, there is limited literature on right colonic resections. We aimed to analyse the short-term outcome of laparoscopic (LRH) and open right hemicolectomy (ORH) in our unit. METHODS: Consecutive patients undergoing elective right hemicolectomies over a period of 28 months were included in the study. No selection criteria were used to allocate the surgical approach. Study parameters included surgical technique, demographic details, ASA grade, body mass index (BMI), length of hospital stay (LOS), post-operative mortality and morbidity, readmission rate and histopathological data. RESULTS: A total of 164 patients underwent right hemicolectomies during the study period (LRH: 89, ORH: 75). Both groups were comparable in age, sex, BMI, ASA grade, tumour stage and lymph node harvest. Four patients (4.5%) in the laparoscopic group required conversion to open surgery. In resections with curative intent, microscopic margins were positive in two patients (3%) in the ORH group compared with one (1%) in the LRH group. Seven ORH patients had an adverse post-operative outcome (three anastomotic leaks, four deaths); there were no deaths/immediate complications in the LRH group (p<0.05). The median LOS for LRH patients (4 days, range: 2-21 days) was significantly shorter than for ORH patients (8 days, range: 3-38 days) (p<0.0001, Mann-Whitney U test). By day 5, 77% of LRH patients were discharged compared with only 21% of patients in the ORH group. There were two readmissions (2.7%) in the ORH group and nine (10.1%) in the LRH group. CONCLUSIONS: Our findings demonstrate advantages in favour of LRH in terms of a shorter hospital stay and reduced post-operative major complications. LRH is safe and should therefore be available to all patients requiring colonic resection. PMID- 22041237 TI - Total adventitial resection of the cardia: 'optimal local resection' for tumours of the oesophagogastric junction. AB - INTRODUCTION: Little is published about the local resection of oesophageal cancers. We adopted the principles of rectal cancer surgery, ie standard surgical dissection techniques as well as standard pathological processing and reporting, and assessed the feasibility of applying them to oesophagogastric junction (OGJ) cancer. METHODS: Over a two-year period consecutive patients with invasive cancers of the OGJ were studied. Following staging and neoadjuvant chemotherapy (NAC), a standard dissection defined as a total adventitial resection of the cardia (TARC) was performed. Standard histopathological processing involved external inking, photographing, transverse slicing and mounting of cut samples on megablocks. Hospital morbidity and mortality as well as survival at five years' follow-up were assessed. RESULTS: Forty consecutive patients had a TARC for OGJ carcinoma. Of these, 32 were offered NAC. Introducing TARC did not result in increased morbidity or mortality. Twenty-seven patients (68%) had an R0 resection that was directly related to the tumour stage and significantly related to a response to chemotherapy. Sixteen patients (42%) were alive five years after their TARC operation. CONCLUSIONS: Although the adventitia of the OGJ is not as well developed as that of the rectum, TARC can be performed safely as a standardised resection for OGJ cancers. Whereas the R0 rate for early stage tumours is very high, it remains disappointingly low for T3N1 tumours despite NAC. Improved long-term survival for these advanced tumours will only be achieved with better neoadjuvant and adjuvant therapies. PMID- 22041238 TI - Management of perforated peptic ulcer in a district general hospital. AB - INTRODUCTION: Laparoscopic surgery has become increasingly popular for elective surgery but it has gained slow transference to emergency surgery. The management of perforated peptic ulcers (PPU) laparoscopically is an accepted strategy yet it still remains infrequently used. The purpose of this study was to analyse the utility and outcomes of laparoscopy versus open repair for PPU in a district general hospital. In addition, we evaluated whether the subspecialty of the on call consultant affected the method of repair performed and the training opportunities for trainee surgeons. METHODS: Between 2003 and 2009, 53 patients underwent laparoscopic repair, 89 patients underwent open repair and a further 20 patients had laparoscopic repair that was converted to open repair for PPU. The results from a prospectively compiled database were analysed with primary outcome measures including operative time, length of hospital stay and mortality. RESULTS: The median operating time in the laparoscopic group was 60.0 minutes compared with 50.5 minutes in the open group. Hospital stay in surviving patients was significantly shorter in patients treated completely laparoscopically (5 days) when compared with the open group (6 days) ( p <0.01). There were six deaths in the laparoscopic group (11%) compared with 13 in the open group (15%) and one in the converted group (5%). Trainees performed 53% (47/89) of open repairs and 13% (7/54) of laparoscopic repairs. CONCLUSIONS: Both laparoscopic and open repair are equally safe in the management of PPU. Our findings support the view that this procedure can be successfully used as a training operation. PMID- 22041239 TI - Increased use of pre-operative imaging and laparoscopy has no impact on clinical outcomes in patients undergoing appendicectomy. AB - INTRODUCTION: The aim of this study was to review changes in the management of acute appendicitis in a ten-year period at a large university teaching hospital in London. METHODS: This was a retrospective cohort study reviewing the medical records of patients who underwent an appendicectomy over a period of 12 months either in 1999 or 2009. Data collected included use of radiological investigations (ultrasonography, computed tomography [CT]), technique of appendicectomy (open [OA] or laparoscopic [LA]), operative time, histopathology and post-operative complications. Univariate and multivariate analysis was performed to assess the influence of variables on the incidence of negative appendicectomy, appendiceal perforation and post-operative complications. RESULTS: All of the patients operated on in 1999 (n=109) had OA. Of the patients operated on in 2009 (n=164), 67 had OA, 91 had LA and 6 had LA converted to OA. None of the patients in 1999 had CT whereas in 2009 26% of patients had CT (sensitivity 94.7%, specificity 75.0%). This increased use of pre-operative imaging had no effect on negative appendicectomy (25.7% vs 12.8%, p=0.445), perforation (30.0% vs 21.3%, p=0.308) or complication rates (9.2% vs 10.4%). The complication rate was also similar regardless of whether patients had OA or LA (11.9% vs 9.9%). Multivariate analysis revealed that age was the only predictor of negative appendicectomy (p=0.029) or perforation (p=0.014). CONCLUSIONS: This study shows that significant increase in the use of pre-operative imaging and laparoscopy in the management of patients with acute appendicitis failed to reduce negative appendicectomy, perforation and complications rates. The patient's age was the only predictor of negative appendicectomy and perforation. PMID- 22041240 TI - Temporary gastric neuromodulation for intractable nausea and vomiting. AB - INTRODUCTION: Gastric neuromodulation (GNM) has been advocated for the treatment of drug refractory gastroparesis or persistent nausea and vomiting in the absence of a mechanical bowel obstruction. There is, however, little in the way of objective data to support its use, particularly with regards to its effects on gastric emptying. METHODS: Six patients (male-to-female ratio: 4:2, mean age: 49 years, range: 44-57 years) underwent the GNM between April and August 2010. Three patients had confirmed slow gastrointestinal transit. Aetiology included previous gastric surgery in two, diabetes in one and idiopathic nausea and vomiting in three patients. GNM pacing wires were placed endoscopically and left in situ for seven days. Patients underwent gastric scintigraphy before and 24 hours after the commencement of GNM. Total gastroparesis symptom scores (TSS), weekly vomiting frequency scores (VFS), health-related quality of life (using the SF-12((r)) questionnaire), gastric emptying, nutritional status and weight were compared before and after GNM. RESULTS: TSS improved after GNM in comparison with baseline data. VFS improved in three of four symptomatic patients. The SF-12((r)) physical composite score improved in four patients (27.5 vs 34.3) and the mental composite score improved in five patients (34.9 vs 35.9). All patients reported an improvement in oral intake. A significant weight gain (mean: 1kg, range: 0.3 2.4kg) was observed over seven days. Gastric emptying half-time improved in four patients. CONCLUSIONS: GNM improved upper gastrointestinal symptoms, quality of life and nutritional status in patients with intractable nausea and vomiting. GNM merits further investigation. PMID- 22041241 TI - The range of the Oxford Shoulder Score in the asymptomatic population: a marker for post-operative improvement. AB - INTRODUCTION: The Oxford Shoulder Score (OSS) is a validated scoring system used to assess the degree of pain and disability caused by shoulder pathology. To date there is no knowledge of the range of the OSS in the healthy adult population. This study aimed to establish the range in asymptomatic individuals. METHODS: The OSS of 100 asymptomatic volunteers was compared with the pre-operative OSS of 100 symptomatic individuals who had had elective shoulder surgery performed at the Royal Preston hospital. RESULTS: The difference in mean scores in the operated group (36.7) and the asymptomatic group (15.3) was statistically significant (p<0.0001). There was, however, a substantial overlap between the scores of the two groups (operated group range: 19-55, asymptomatic group range: 12-47). Factors such as age, sex, body mass index, co-morbidities and smoking did not have a statistically significant impact on the eventual score in the asymptomatic group. CONCLUSIONS: This study has established the range of OSS in the asymptomatic adult population. Symptom scores can only be used effectively when the range in the asymptomatic population is known. This is so that disease severity can be gauged in the context of the normal population and post-operative improvements can be forecast more accurately. PMID- 22041242 TI - Validation of a one-stop carpal tunnel clinic including nerve conduction studies and hand therapy. AB - INTRODUCTION: Carpal tunnel syndrome is the most common hand disorder. We describe a pathway that includes clinical assessment, neurophysiological testing, surgery and physical therapy all at the same visit. METHODS: All referrals for carpal tunnel syndrome were screened for inclusion in a 'one-stop' surgeon-led clinic. Prospective clinical data collected included patient reported outcome measures and satisfaction scores, touch threshold, pinch and grip strength. Patients were assessed clinically, underwent nerve conduction studies and surgery as indicated, all on the same day. Baseline and one-year follow-up data were analysed for 57 patients (62 hands). RESULTS: There was significant improvement in all domains of the Boston Carpal Tunnel and Michigan hand Outcomes questionnaires, grip strength and touch threshold. There were no adverse events. The total mean operating time was 12.8 minutes (range: 5-15 minutes) and the mean tourniquet time was 2.5 minutes (range: 1-11 minutes). Using a dual theatre model produced a short mean turnaround time of 14.8 minutes (range: 2-37 minutes). Patient satisfaction as judged using a Picker questionnaire was very high. CONCLUSIONS: A highly efficient clinical service involving both diagnostics and treatment can be delivered at a single hospital visit while maintaining optimal outcomes and high patient satisfaction. PMID- 22041243 TI - Computed tomography versus ureteroscopy in identification of renal tract stone with ureteral stent in situ. AB - INTRODUCTION: The aim of this study was to validate the use of non-contrast computed tomography (CT) with a ureteral stent in situ instead of ureteroscopy for identification of renal tract stones. METHODS: All patients who had stents inserted for renal tract stones and underwent non-contrast CT with the stent in situ followed by ureteroscopy between May 2008 and October 2009 at The Canberra hospital, Australia, were analysed retrospectively. Statistical analysis was performed to compare any differences between CT and ureteroscopy in the identification of stones. RESULTS: Overall, 57 patients were included in the study. The difference between CT and ureteroscopy findings was statistically significant. CT identification of stones with a stent in situ had a sensitivity of 86%, a specificity of 46%, a positive predictive value of 63%, a negative predictive value of 76% and an accuracy of 67%. CONCLUSIONS: Our study suggests that non-contrast CT is inferior to the 'gold standard' of ureteroscopy. It lacks sensitivity, specificity, positive predictive value, negative predictive value and accuracy. Therefore, we cannot recommend using non-contrast CT to replace ureteroscopy. PMID- 22041245 TI - A simple method of securing the safety wire during ureteroscopy. PMID- 22041246 TI - Vacuum-assisted sterile drainage of large post-operative seromas: the Royal Marsden technique. PMID- 22041247 TI - External rotation of the draining vein improves flow in arteriovenous fistulas. PMID- 22041248 TI - Improving the success of nipple reconstruction. PMID- 22041249 TI - Tension free vaginal tape in static facial reanimation: new use for a well tested device. PMID- 22041250 TI - Keeping the shoulder arthroscopy patient dry. PMID- 22041251 TI - Positioning for elbow fixation in young children. PMID- 22041252 TI - Simple technique for closure of skin lacerations under tension. PMID- 22041253 TI - Field effect of two commercial preparations of botulinum toxin type A: a prospective, double-blind, randomized clinical trial. AB - BACKGROUND: The dose equivalence of commonly used commercial preparations of botulinum toxin type A, Dysport (abotulinumtoxinA [ABO] 500 U, Ipsen Biopharm Limited, Wrexham, United Kingdom) and Botox (onabotulinumtoxinA [ONA] 100 U, Allergan, Irvine, CA), remains unclear. OBJECTIVE: We sought to evaluate the field effect for ABO and ONA at dose equivalences of 2.5:1.0 U and 2.0:1.0 U, in both muscular and sweat gland activity. METHODS: In all, 59 female patients with forehead wrinkles were enrolled. Patients were randomized for dose equivalence between ABO and ONA, group A (2.0:1.0 U, ABO:ONA) or group B (2.5:1.0 U, ABO:ONA) administered in the frontalis muscles. Clinical assessment, Minor test, and electromyography evaluations were performed at baseline, 28 days, and 112 days. RESULTS: In group B, the field of anhidrotic effect of ABO showed a greater area and larger horizontal diameter than ONA at 28 and 112 days. At maximum frontalis muscle activity (day 112) patients receiving ABO demonstrated greater improvement based on the Wrinkle Severity Scale. No differences were found in frontalis muscle activity at rest between groups A and B based on results of Wrinkle Severity Scale, electromyography, and interindividual variability data at 28 and 112 days. LIMITATIONS: Currently, there are no objective measurements other than electromyography to evaluate the field effect of botulinum toxin type A in muscles. CONCLUSION: At a dose equivalence of 2.0:1.0 U (ABO:ONA), similar field effects were found for both muscle and sweat gland activity. At a higher dose equivalence of 2.5:1.0 U (ABO:ONA), injections of ABO showed greater area and larger horizontal diameter in field of anhidrotic effect at 28 and 112 days than ONA. PMID- 22041254 TI - Physician Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI): why do both? A systematic analysis of randomized controlled trials of biologic agents for moderate to severe plaque psoriasis. AB - BACKGROUND: Although there are many psoriasis assessment tools currently published, one of the unmet needs in psoriasis research remains consensus about the single best validated and reproducible assessment tool. OBJECTIVES: In this systematic review we sought to determine the degree of correlation between two commonly used psoriasis assessment tools, the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). METHODS: Randomized controlled systemic trials in moderate to severe psoriasis were reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We recorded and compared the percent of patients achieving both 75% reduction in PASI score (PASI 75) and PGA 0 or 1 (clear or almost clear) at 8 to 16 weeks, 17 to 24 weeks, and greater than 24 weeks of treatment with the investigational drug. RESULTS: Our literature review yielded 30 randomized controlled trials using biologic agents in moderate to severe psoriasis. We found that the two assessment tools correlate very tightly except at the lower bounds of therapeutic efficacy. The r(2) values for the correlation between PASI 75 and a score of clear or almost clear on the PGA were 0.9157 at 8 to 16 weeks and 0.892 at 17 to 24 weeks. LIMITATIONS: Limitations of our study include the small number of randomized controlled trials publishing the percent of patients achieving 75% reduction in PASI score and a score of clear or almost clear on the PGA after 24 weeks of therapy. In addition, our results are not generalizable beyond the patients with moderate to severe plaque psoriasis. CONCLUSION: The two assessment tools are substantially redundant and either alone is a sufficient tool for assessing psoriasis severity in patients with moderate to severe disease. Because the PASI is better validated and more detailed, it remains the score of choice for clinical trials, but the simpler PGA may be well suited for community-based outcomes projects. PMID- 22041255 TI - Pregnancies exposed to methadone, methadone and other illicit substances, and poly-drugs without methadone: a comparison of fetal neurobehaviors and infant outcomes. AB - BACKGROUND: It is suspected that there is a continuum of impairment among prenatally drug-exposed infants, such that opioid and/or poly-drug exposure confers the highest risk for adverse neonatal outcomes than other classes of substances or single substance exposures. Suitable control groups are difficult to identify. This study compared fetal neurobehavioral development and infant outcomes in offspring of three groups of pregnant women in drug treatment. Exposure groups include: Methadone+other illicit substances (MM+Poly) and two groups currently abstinent for poly drug exposures: Methadone only (MM/A) and Non Methadone (NM/A). METHODS: Forty-nine women (19 MM+Poly, 18 MM/A, and 12 NM/A) underwent fetal monitoring at 36 weeks gestation at peak and trough levels of methadone (MM+Poly; MM/A) or at comparable morning and afternoon times (NM/A). Fetal heart rate (FHR), heart rate variability (FHRV) and motor activity (FM) data were collected. Infant measures included birth outcomes and Neonatal Abstinence Syndrome (NAS) assessment. RESULTS: As compared to the NM/A group, cardiac measures were decreased in methadone-exposed fetuses at peak levels. FHR was significantly more suppressed in the MM+Poly group. FM was significantly lower in the MM/A vs. the NM/A group at both peak and trough, indicative of more persistent exposure effects. The MM+Poly group delivered 1 week earlier and required NAS pharmacological treatment twice as often as the MM/A group. CONCLUSIONS: Results support the notion that poly-drug exposure may potentiate the effects of methadone on the fetus and infant and highlights the need for intensified treatment for methadone-maintained women who abuse other substances. PMID- 22041256 TI - A preliminary study of the neural effects of behavioral therapy for substance use disorders. AB - BACKGROUND: The mechanisms by which behavioral therapies for substance use disorders (SUDs) exert their effects and the components of treatment that contribute most to substance use outcome remain unclear. Disruptions to aspects of impulse control and attention have been hypothesized to contribute to the development and maintenance of addiction; moreover, alterations in these processes may underlie responses to treatment. METHODS: Individuals participating in a randomized clinical trial evaluating computer-assisted cognitive behavioral therapy (CBT) for substance abuse participated in fMRI Stroop before and after treatment. A non-substance-using comparison group performed the same task under test-retest conditions. RESULTS: The patient group demonstrated decreased Stroop related BOLD signal in regions including the anterior cingulate, inferior frontal gyrus and midbrain at post-treatment relative to pre-treatment, and displayed a greater decrease in the subthalamic nucleus and surrounding regions compared to healthy controls following test-retest. CONCLUSIONS: Behavioral therapies may be associated with reduction in substance use and effects on neural systems involved in cognitive control, impulsivity, motivation and attention. PMID- 22041259 TI - [Control of hypertension in patients with chronic kidney disease]. PMID- 22041260 TI - [Pay attention to the application of Doppler echocardiography in intensive care unit]. PMID- 22041261 TI - [Updated interpretation of the classification of chronic kidney disease]. PMID- 22041262 TI - [Certain issues concerning continuous ambulatory peritoneal dialysis in patients with cirrhosis]. PMID- 22041263 TI - [The relationship between urinary albumin excretion and serum uric acid in general population]. AB - OBJECTIVE: To investigate the relationship between the urinary albumin excretion (UAE) and serum uric acid in general population. METHODS: The study participants were derived from the epidemiological study on the association of metabolic syndrome and chronic kidney disease (CKD) in Pinggu district, Beijing. A total of 992 participants (463 men and 529 women) aged from 30 to 75 years were enrolled in this study. For each participant, UAE, serum uric acid, serum creatinine, and serum lipids were detected and other potential risk factors for CKD were surveyed. RESULTS: (1) The frequencies of microalbuminuria, macroalbuminuria and hyperuricemia were 12.9%, 1.8% and 4.3% respectively. The persons with hyperuricemia had significantly higher frequency of albuminuria than those without hyperuricemia (37.2% vs 13.7%, P < 0.01). (2) The participants were divided according to the quartiles (25%, 50%, 75%) of serum uric acid level, and the frequencies of albuminuria in males were 13.2%, 13.9%, 17.2% and 25.4%, while those in females were 8.4%, 6.2%, 9.6% and 24.8%. (3) Multivariate logistic regression analysis showed, hyperuricemia was significantly associated with albuminuria in females (OR = 2.31, 95%CI 1.15-4.68; P = 0.02), but not in males. If the persons with reduced renal function were excluded, similar result still could be gained. CONCLUSIONS: The prevalence of albuminuria increases gradually with uric acid elevation. Serum uric acid is an independent risk factor of elevated UAE, especially in females. PMID- 22041264 TI - [The correlation between uric acid and the incidence and prognosis of kidney diseases: a systematic review and meta-analysis of cohort studies]. AB - OBJECTIVE: To evaluate the association of serum uric acid and the incidence and prognosis of kidney diseases systematically, so as to provide reference for the treatment and prevention of kidney diseases. METHODS: Literatures related to the associations between serum uric acid and incidence and prognosis of kidney diseases were selected from the Chinese Biomedical Literature Database (CBM) (January 1982 to March 2010), EMBASE (January 1966 to March 2010) and Medline (January 1950 to March 2010) for cohort studies. Two researchers independently screened the studies, assessed the risk of bias of included studies using the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and extracted data. Stata 10.0 was used to calculate the pooled relative risk. RESULTS: Twenty-one eligible cohort studies were selected, of which 11 on incidence of kidney diseases (n = 276 801), and 10 on the prognosis of kidney diseases (n = 3004). Meta analysis was performed based on data influencing incidence and prognosis factors of kidney diseases except for serum uric acid. The results showed, (1) uric acid and incidence of kidney diseases: hyperuricemia could increase the risk of kidney diseases (RR = 1.49, 95%CI 1.27 - 1.75); (2) uric acid and prognosis of patients with kidney diseases:hyperuricemia could deteriorate the kidney function (RR = 1.35, 95%CI 1.12 - 1.63) and increase the risk of mortality (RR = 1.67, 95%CI 1.29 - 2.16). CONCLUSION: Uric acid is an independent risk factor for incidence of kidney diseases and poor prognosis of patients with kidney diseases. Further high quality clinical trials with long-term follow up should be conducted to determine whether lowering uric acid levels would be of clinical benefit in the prevention and treatment of kidney diseases, so as to provide direct evidence for clarifying correlation between uric acid and kidney diseases and the prevention and treatment for patients with high uric acid. PMID- 22041265 TI - [Total parathyroidectomy in treatment of Sagliker syndrome in 10 cases of hemodialysing patients with secondary hyperparathyroidism]. AB - OBJECTIVE: To evaluate the efficacy of the parathyroidectomy (PTX) in the treatment of severe secondary hyperparathyroidism (SHPT) with Sagliker syndrome (SS). METHODS: A retrospective review was undertaken among 212 SS patients underwent PTX in our hospital and with more than 3 years' follow up. The definitions of the efficacy were based on the postoperative intact parathyroid hormone level (iPTH). "Cure" showed that the iPTH was < 150 ng/L; "marked effectiveness" was 150 - 300 ng/L; "effectiveness" was 301 - 500 ng/L; "ineffectiveness" was > 500 ng/L. The status was defined as persistent SHPT if iPTH was > 150 ng/L after surgery. The status was considered as SHPT recurrence if iPTH was < 100 ng/L in the first week after surgery, and gradually increased and > 150 ng/L with the follow-up. RESULTS: (1) Ten patients were involved and the average dialysis time was 142 months [male/female: 4/6; age 30 - 54 (39.3 +/- 10.4) years]. All patients had severe bone and joint pain, accompanied with progressive facial increases, chicken breast, kyphosis, hip bone deformities, and body height shortening. (2) Preoperative tests: the median of iPTH 2000 (1800 - 2863) ng/L; serum calcium (2.45 +/- 0.21) mmol/L, phosphorus (2.19 +/- 0.51) mmol/L, alkaline phosphatase (ALP) (1189.8 +/- 780.0) IU/L. Two to four enlarged parathyroid glands were confirmed by ultrasound and (99)Tc(m)-MIBI parathyroid scintigraphy. (3) Surgical procedures: local or general anesthesia for PTX. Supplement with calcium and calcitriol implemented low serum calcium after PTX. (4) FOLLOW-UP: symptoms, including bone pain, muscle weakness, skin itching, and insomnia, were significantly improved after surgery. Transient hoarseness occurred in 2 cases. The iPTHs of all patients were decreased significantly after surgery. The median of iPTH was 55.5 (10 - 967) ng/L at 1 month post PTX, and was significantly less than prior to PTX (P < 0.001). Eight patients were "cure", 1 "marked effectiveness", and 1 "ineffectiveness". Two patients were persistent SHPT, and 1 died of heart failure in the 4(th) year after PTX. The development of bone deformities was stopped and malnutrition was improved in long-time follow up. The level of iPTH 135 (28 - 390) ng/L (P < 0.001), serum calcium, phosphorus, and ALP showed normal in the third year. The SHPT recurrence was appeared in the 2(nd) and 3(rd) year in 2 out of 8 patients, respectively. CONCLUSIONS: Total PTX can effectively treat SS by SHPT. It can improve prognosis for patients, such as bone pain disappearing, bone deformities stopping and malnutrition improving, etc. The level of iPTH may rise again in some patients in the future. Therefore, more attentions should be paid to monitoring. PMID- 22041266 TI - [The risk factors for worsening renal function in patients with chronic heart failure]. AB - OBJECTIVE: To investigate the risk factors of worsening renal function (WRF) in patients with chronic heart failure (CHF) and WRF influence on prognosis. METHODS: A case-control study were undertaken to analyze independent risk factor statistically related to incidence of WRF, and to assess the influence of WRF on prognosis. RESULTS: The independent predictors of WRF were creatinine level at admission (OR 2.248, 95%CI 1.088 - 4.647, P = 0.029) and NYHA class on admission (OR 2.485, 95%CI 1.385 - 4.459, P = 0.002). The mortality of patient with WRF was obviously higher than that of control group during hospitalization (OR 3.824, 95%CI 2.452 - 5.637, P < 0.015). CONCLUSIONS: WRF is a common complication among patients hospitalized for CHF, and is obviously associated with mortality during hospitalization. Higher creatinine level and weak heart function are independent risk factors for incidence of WRF of patients with CHF. PMID- 22041267 TI - [The clinical analysis of nephrotic syndrome after allogeneic hematopoietic stem cell transplantation in one single center]. AB - OBJECTIVE: To explore the incidence, diagnosis and treatment of nephrotic syndrome (NS) following allogeneic hematopoietic stem cell transplantation (allo HSCT) in one single center. METHODS: Analysis were carried out based on the records of 1464 patients following allo-HSCT hospitalized in Peking University People's Hospital from January 1996 to April 2009, so as to evaluate the incidence and outcomes of NS. A total of 1464 patients whose survival time was longer than 100 d were enrolled. Eight patients (0.6%) had NS following allo HSCT. Using the nested case-controlled study, 56 cases who received transplantation within the same period were selected as control group for risk factors analysis. RESULTS: The median time of NS was 488 (54 - 1185) d after allo HSCT. Lower extremities' edema and heavy proteinuria were present in all the patients. Two patients were accompanied with impaired renal function. Six patients suffered from chronic graft-versus-host disease (GVHD). Three patients with NS were accompanied with other symptoms of GVHD. Renal biopsy examination showed typical features of minimal change diseases in 3 patients and membranous nephropathy in 1 patient. All cases achieved complete remission (CR) after taking combined immunosuppressant agents. One patient relapsed soon after all the immunosuppressant agents were stopped. Six patients were still surviving with disease free. One patient died of the relapse of leukemia and another patient died of early discharge from hospital after allo-HSCT. The possible factors correlated with the occurrence of NS were analyzed, and the occurrence of chronic GVHD was identified as an independent factor of NS. CONCLUSIONS: NS should be carefully taken into consideration when edema and proteinuria are present in patients following allo-HSCT. The occurrence of NS is probably related with chronic GVHD. NS responds well to immunosuppressant agents. PMID- 22041268 TI - [The clinical and pathologic features of vascular amyloid deposits of amyloid nephropathy in 6 patients]. AB - OBJECTIVE: To analyze clinical and pathologic features of a rare vascular amyloid deposits of amyloid nephropathy (VADAN) in 6 patients, so as to improve its diagnosis and treatment. METHODS: All patients received immunopathology, microscopy and electron microscopy examination, and amyloid types were analyzed. RESULTS: There were 3 males and 3 females with ages ranging from 52 to 73 years. Two patients suffered from multiple myeloma. Majority patients had slight albuminuria and hematuria. One patient combined with minimal change glomerular disease presented nephrotic syndrome. One patient combined with IgA nephropathy had albuminuria and hematuria. And one patient had myeloma cast nephropathy with acute renal failure. Kidney biopsy proved amyloid deposits along interlobular arterial wall only in all 6 patients. Two cases secondary from multiple myeloma were kappa amyloid, and the rests were lambda amyloid. CONCLUSIONS: VADAN is a rare type of amyloid nephropathy. Its clinical manifestation is different from common amyloid nephropathy. Kidney biopsy will benefit its differential diagnosis. PMID- 22041269 TI - [The effect of fasudil via Rho/ROCK signaling pathway on the inflammation and fibrosis in human mesangial cells in high glucose medium]. AB - OBJECTIVE: To study the effect of fasudil on inhibiting the Rho/ROCK signaling pathway under high glucose in human mesangial cells (HMCs) inflammation and fibrosis. METHODS: Synchronized HMCs were divided into following groups: (1) Normal glucose control group (NG, 5.5 mmol/L glucose); (2) High glucose group (HG, 30 mmol/L glucose); (3) Mannitol group (Man, 5.5 mmol/L glucose + 24.5 mmol/L mannitol); (4) High glucose + fasudil group (HG + F, the concentrations of fasudil were 25, 50 and 100 umol/L, respectively). Collect the supernatant and cells at 0, 12, 24, 36, 48 and 72 h respectively, and determine the concentration changes of the RhoA, ROCK-I, connective tissue growth factor (CTGF)mRNA with real time PCR method in the cells, then used the ELISA method to check the protein content of the fibronectin (FN), CTGF, TNFalpha in the supernatant. RESULTS: (1) RhoA, ROCK-I and CTGF mRNA of the HMCs cultured under the high glucose expressed significantly higher than those in the normal group, and there was certain time dependence. Besides, there was no statistic significance by comparing Man and NG. (2)Under the high glucose situation, after the fasudil pretreatment with different concentrations and 24 h or 48 h culture with high glucose, RhoA, ROCK I, CTGF mRNA expression was significantly decreased in HG + F, compared with HG, and there was certain concentration-dependence. (3) High glucose increased the FN, CTGF, TNFalpha protein secretion of HMCs in a time-dependent manner, but normal glucose and mannitol had no such effect. (4) After the fasudil pretreatment with different concentrations and culture with high glucose for 12, 24, 36, 48, 72 h, the FN, CTGF, TNFalpha protein secretion was significantly reduced compared with HG. CONCLUSION: Fasudil can reduce the secretion of downstream inflammatory factors and cytokines by inhibiting high glucose activated HMCs Rho/ROCK signaling pathway, and reduce the inflammation and fibrosis of HMCs. This provides a new basis for the therapeutic target in the treatment of diabetic nephropathy. PMID- 22041270 TI - [The clinical outcomes of patients undergoing revascularization for acute coronary syndrome]. AB - OBJECTIVE: To evaluate short-term and long-term prognosis of revascularization in patients with acute coronary syndrome. METHODS: A total of 6005 patients who received coronary revascularization in our institution between July 2003 and September 2005 were enrolled. The patients were followed up in clinic or by telephone after discharge between September 2006 and November 2006. The clinical and prognosis data of all-cause mortality, neo-myocardial infarction, nonfatal stroke, and re-revascularization of ST-segment elevation myocardial infarction (STEMI), non ST-segment elevation myocardial infarction (NSTEMI) and major adverse cardiovascular and cerebrovascular events (MACCE) were analyzed. RESULTS: Among 4865 acute coronary syndrome patients, 955 cases were STEMI; 263 cases were NSTEMI; and 3647 cases were unstable angina (UA) pectoris. There were no significant difference for in-hospital mortality and late mortality (18 month survival 96%, 98% and 98%) between patients with STEMI, NSTEMI and UA. Patients with UA had lower MACCE rate (18 month non-MACCE survival of STEMI, NSTEMI and UA group were 86%, 86%, and 89% respectively). CONCLUSIONS: Despite different clinical characteristics, patients with STEMI, NSTEMI and UA undergoing revascularization had similar short-term and long-term mortality. Patients with UA had lower MACCE rate. PMID- 22041271 TI - [The clinicopathologic analysis in autopsy patients with cardiovascular disease]. AB - OBJECTIVE: To investigate the clinical autopsy results of patients died of cardiovascular disease or other disease complicated with cardiac damage. METHODS: Complete autopsy was performed on 86 cases with uncertain cause of death. Through integrating clinical diagnosis and treatment with gross autopsy findings and microscopic observations, 86 autopsies were determined the major cause of death. RESULTS: In 86 autopsies, 69 cases were heart disease. Differences between pathological diagnosis and clinical diagnosis were compared. Twenty-seven cases were cardiac deaths, with diagnosis accordance rate of 81.5%. Forty-two cases died of non-cardiac disease but complicated with heart disease or involving the heart which accelerated the death in patients, with accordance rate of 78.6%. CONCLUSION: Scientific and correct performance of autopsy was important to determine the causes of death, to promote development of related disciplines and to improve the diagnosis and treatment of the diseases. PMID- 22041272 TI - [The clinical application of pulmonary vascular permeability index on differential diagnosis of acute pulmonary edema]. AB - OBJECTIVE: To assess the value of pulmonary vascular permeability index in differentiating acute lung injury (ALI) from cardiac pulmonary edema. METHODS: Critically ill patients with acute pulmonary edema were included from May, 2004 to September, 2008. Patients were divided into two groups, the ALI group and the cardiac pulmonary edema group (C group). Pulmonary vascular permeability index (PVPI), intrathoracic blood volume (ITBVI) were determined by pulse indicator continuous cardiac output (PiCCO) system. RESULTS: (1) Thirty-four patients were enrolled, 22 cases in ALI group and 12 cases in C group. (2) The PVPI in patients of ALI group (2.7 +/- 1.4) was higher than that of C group (1.9 +/- 0.6; P < 0.05). EVLWI and ITBVI did not have the significant difference between the two groups (P > 0.05). (3) PVPI was positively correlated with EVLWI (r = 0.762), negatively correlated with PaO2/FiO2 (r = -0.478). (4) ARDS was diagnosed in 13 cases, including 8 pulmonary cause (ARDSp) and 5 extra-pulmonary cause (ARDSexp). PVPI, EVLW/ITBV and EVLWI of patients with ARDSexp were obviously higher than those with ARDSp. CONCLUSIONS: PVPI may be useful for differentiating the types of pulmonary edema in the critically ill. PMID- 22041273 TI - [A comparative study of incidence and prevalence of Crohn's disease in mainland China in different periods]. AB - OBJECTIVE: To collect data and analyze the current status and prevalence changes of Crohn's disease (CD) in mainland China in recent decades. METHODS: A computer based literature search was previously performed by using 50-year (1950 to 2002) of records of CD from the Chinese Database of Biology and Medicine (CBM) (1979 to 2002) and a manual year-by-year search of the literature (1950 to 1978). Using similar method, descriptive epidemiological data from 2003 to 2007 were collected, analyzed and compared with previous research. RESULTS: Four hundred and seventeen relevant papers during 2003 and 2007 were collected and 62 papers were eligible for inclusion. Within 62 papers, a total of 2149 cases with CD from 2003 to 2007 have been reported nationwide, comprising 1288 male and 861 female patients, with a 1.50:1 male predominance, and indicating 1.41 time of increment as compared with our previous result (ie, 1526 cases from 1950 - 2002). There were no obvious changes in incidence age (younger and middle age were main components) and sex ratio (number of male was still larger than that of female). The extrapolated CD incidence and prevalence rates were 1.21/100 000 person.year and 2.29/100 000, respectively, which were higher than that of year 1950 - 2002, 0.28/100 000 person.year and 1.38/100 000, respectively. CONCLUSIONS: The incidence and prevalence rates of CD have been increasing rapidly, but these rates are still lower than those in Western world. PMID- 22041274 TI - [The clinical evaluation of piperacillin and sulbactam sodium in treatment of respiratory, urinary tracts and other infections in 579 patients]. AB - OBJECTIVE: To evaluate the clinical efficacy and safety of piperacillin and sulbactam sodium combinations in the treatment of common infections. METHODS: This was a multi-centre, prospective and open study. All subjects from 57 wards caught common infection like respiratory (RTI) or urinary diseases (UTI). The dosages of piperacillin and sulbactam sodium combinations 2.5 g injection were determined according to indications: for adult, 2.5 g or 5 g per time, 2 time/day; for severe or obstinate infection, 2.5 g or 5 g per time, 3 time/day. General information, clinical response pre- and post-treatment, infected locus, drug recipe and protocol, prognosis and adverse reaction were recorded. RESULTS: Data of 579 cases were collected with 388 males and 191 females. The average age was (66.8 +/- 17.0) years. There were 500 patients who were suffering with RTI, with 362 cases of pneumonia, 102 of acute exacerbation of chronic bronchitis, and 36 of other infections. There were 50 cases with UTI, with 31 of simple urinary tract infection, and 19 of complex urinary tract infection. In addition, there were 9 cases of combined RTI and UTI, and 20 of other infections including peritonitis. The average duration of anti-microbial for RTI and UTI was (8.65 +/- 3.78) days and (7.45 +/- 3.46) days respectively with the total efficacy rate was 92.6% and 98.0% respectively for RTI and UTI. The incidence of adverse events was only 0.86% (5 cases), including nausea, rash, itching, ALT elevation and suspected drug induced fever in each one. CONCLUSION: Piperacillin and sulbactam sodium compound had high clinical efficacy and safety in the treatment of common infections including RTI and UTI. PMID- 22041275 TI - [The effects of pronase on drugs concentrations for treatment of Helicobacter pylori infection in gastric tissue]. AB - OBJECTIVE: To evaluate the effect of pronase on amoxicillin and metronidazole concentrations in gastric tissue. METHODS: C57BL/6 mice were randomly divided into experimental group (n = 70) and control group (n = 70). Amoxicillin (28.6 mg/kg), metronidazole (22.5 mg/kg) and omeprazole (138.2 mg/kg) were administered orally to C57BL/6 mice, combined with pronase (110 mg/kg) or same amount of sterile PBS. Gastric tissue and blood plasma samples were taken at 10 point-in time (7 mice/time) from 15 min up to 360 min after administration. Concentrations of amoxicillin and metronidazole were detected by high performance liquid chromatography. Gastritis index of gastric mucosa (hematoxylin-eosin staining) and the gastric tissue expressions of mucin 5AC (Western blot) were detected at 120 min and 360 min after administration. RESULTS: The time to peak concentration of amoxicillin and metronidazole in gastric tissue appeared earlier than that in blood plasma (15 min vs 60 min). Tissue concentrations of amoxicillin and metronidazole of experimental group were significantly higher than those of control, and they were mainly at 15 min to 90 min (P < 0.05). Plasma concentrations of amoxicillin and metronidazole of experimental group at 15 min and 30 min were higher than those of control (P < 0.05). There was no difference in gastritis index between experimental group and control at 120 min and 360 min after administration (0.28 +/- 0.18 vs 0.14 +/- 0.14, P > 0.05; 0.43 +/- 0.20 vs 0.28 +/- 0.18, P > 0.05). The expressions of mucin 5AC in experimental group were lower than those of control (0.036 +/- 0.006 vs 0.197 +/- 0.058; P < 0.05; 0.039 +/- 0.008 vs 0.208 +/- 0.072, P < 0.05). CONCLUSIONS: Pronase can significantly enhance the drugs penetration from mucus into gastric tissue. Concentrations of amoxicillin and metronidazole of experimental group in local gastric tissue and plasma are higher than those of control, especially in improving concentrations of gastric tissue and prolongation of exposed time. PMID- 22041276 TI - Brucellosis Ontology (IDOBRU) as an extension of the Infectious Disease Ontology. AB - BACKGROUND: Caused by intracellular Gram-negative bacteria Brucella spp., brucellosis is the most common bacterial zoonotic disease. Extensive studies in brucellosis have yielded a large number of publications and data covering various topics ranging from basic Brucella genetic study to vaccine clinical trials. To support data interoperability and reasoning, a community-based brucellosis specific biomedical ontology is needed. RESULTS: The Brucellosis Ontology (IDOBRU: http://sourceforge.net/projects/idobru), a biomedical ontology in the brucellosis domain, is an extension ontology of the core Infectious Disease Ontology (IDO-core) and follows OBO Foundry principles. Currently IDOBRU contains 1503 ontology terms, which includes 739 Brucella-specific terms, 414 IDO-core terms, and 350 terms imported from 10 existing ontologies. IDOBRU has been used to model different aspects of brucellosis, including host infection, zoonotic disease transmission, symptoms, virulence factors and pathogenesis, diagnosis, intentional release, vaccine prevention, and treatment. Case studies are typically used in our IDOBRU modeling. For example, diurnal temperature variation in Brucella patients, a Brucella-specific PCR method, and a WHO-recommended brucellosis treatment were selected as use cases to model brucellosis symptom, diagnosis, and treatment, respectively. Developed using OWL, IDOBRU supports OWL based ontological reasoning. For example, by performing a Description Logic (DL) query in the OWL editor Protege 4 or a SPARQL query in an IDOBRU SPARQL server, a check of Brucella virulence factors showed that eight of them are known protective antigens based on the biological knowledge captured within the ontology. CONCLUSIONS: IDOBRU is the first reported bacterial infectious disease ontology developed to represent different disease aspects in a formal logical format. It serves as a brucellosis knowledgebase and supports brucellosis data integration and automated reasoning. PMID- 22041277 TI - Optimization of a protocol for cryopreservation of mouse spermatozoa using cryotubes. AB - The rapid increase in the number of genetically modified mouse strains has produced a high demand for their frozen spermatozoa from laboratories and mouse banking facilities. Historically, plastic straws have been used preferentially as containers for frozen mammalian spermatozoa because spermatozoa frozen in plastic straws have a high survival rate after thawing. However, plastic straws are more fragile and are used less often than the cryotubes used for conventional cell freezing. In this study, we sought to develop a new protocol for sperm freezing using cryotubes as the container to increase the accessibility of mouse sperm cryopreservation. Epididymal spermatozoa were collected from mature ICR or C57BL/6J (B6) males and were suspended in 18% raffinose and 3% skim milk solution. We then optimized the following conditions using the sperm survival rate as an index: 1) distance of cryotubes from the surface of the liquid nitrogen at freezing, 2) volume of the sperm suspension in the cryotube and 3) temperature of warming sperm during thawing. The best result was obtained when cryotubes containing 10 ul of sperm suspension were immersed 1 cm below the surface of the liquid nitrogen and then thawed at 50 C. The fertilization rates using spermatozoa frozen and thawed using this method were 63.1% in ICR mice and 28.2% in B6 mice. The latter rate was increased to 62.3% by adding reduced glutathione to the fertilization medium. After embryo transfer, 68% and 62% of the fertilized oocytes developed into normal offspring in the ICR and B6 strains, respectively. These results show that cryotubes can be used for cryopreservation of mouse spermatozoa under optimized conditions. This protocol is easy and reproducible, and it may be used in laboratories that do not specialize in sperm cryopreservation. PMID- 22041279 TI - Transmitochondrial mice as models for mitochondrial DNA-based diseases. AB - Mitochondrial genome (mtDNA) mutations and the resultant mitochondrial respiratory abnormalities are associated with a wide variety of disorders, such as mitochondrial diseases, neurodegenerative diseases, diabetes, and cancer, as well as aging. Generation of model animals carrying mutant mtDNAs is important for understanding the pathophysiological mechanisms of the mtDNA-based diseases. We have succeeded in generating three kinds of mice with pathogenic mutant mtDNAs, named "mito-mice," by the introduction of mitochondria carrying pathogenic mutant mtDNAs into mouse zygotes and mouse embryonic stem (ES) cells. In the case of mito-mice possessing the heteroplasmic state of wild-type mtDNA and pathogenic mtDNA with a large-scale deletion (DeltamtDNA, mito-miceDelta), a high load of DeltamtDNA induced mitochondrial respiration defects in various tissues, resulting in mitochondrial disease phenotypes, such as low body weight, lactic acidosis, ischemia, myopathy, heart block, deafness, male infertility, long-term memory defects, and renal failure. In this review, we summarize generation and clinical phenotypes of three types of mito-mice and we introduce several treatment trials for mitochondrial diseases using mito-miceDelta. PMID- 22041280 TI - Roles of serine protease inhibitor Kazal type 1 (SPINK1) in pancreatic diseases. AB - Serine protease inhibitor Kazal type 1 (SPINK1) was originally identified as a trypsin inhibitor by Kazal et al. in 1948. SPINK1 is strongly elevated in pancreatitis and the elevation correlates with the severity of disease. In 2000, mutations in the SPINK1 gene were shown to be associated with chronic pancreatitis. Since then, there have been many reports on association between mutations in the SPINK1 genes and patients with pancreatitis. In 1982, SPINK1 was shown to be identical to tumor associated trypsin inhibitor (TATI). In addition, sequence similarities were detected between human epidermal growth factor (EGF) and human SPINK1 in 1983. Actually, SPINK1 was shown to stimulate growth of several cell lines including cancer cells in 1985. Recent clinical studies showed that high levels of SPINK1 protein in serum or urine were associated with adverse outcome in various cancer types. However, there was little evidence that showed in vivo function of SPINK1. Surprisingly, mice deficient in Spink3 (a mouse homologue gene of human SPINK1) showed excessive autophagy, but not pancreatitis in the exocrine pancreas, leading to autophagic cell death. We also demonstrated that SPINK1 acts as a growth factor through EGFR signaling. These data indicate that the role of the SPINK1 is not just as a trypsin inhibitor, but also as a growth factor as well as a negative regulator of autophagy. In this review, we summarize the roles of SPINK1/Spink3 in pancreatic diseases based on the data obtained from analyses using mouse models. PMID- 22041281 TI - Quinestrol treatment induced testicular damage via oxidative stress in male Mongolian gerbils (Meriones unguiculatus). AB - The hypothesis that quinestrol exerts testicular damage via oxidative stress was investigated in male gerbils using a daily oral gavage of 3.5 mg/kg body weight for 2 weeks (the multidose-treated group) or 35 mg/kg body weight (the single dose-treated group). The testicular histological morphology, antioxidant capacity and malondialdehyde (MDA) concentration in testicular tissue and plasma were assessed at 15, 30, and 60 days following treatment. The results showed that the activity of the antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxide (GSH-Px), and total antioxidant capacity (T-AOC), at 15 days after treatment in testicular tissue decreased, which led to the MDA concentration increasing while at the same time germ cells were rarefied and showed an irregular distribution in seminiferous tubules of quinestrol-treated gerbils. At 30 days, the testicular weight and antioxidant capacity continued to decrease, while the MDA concentration continued to increase, and testicular histopathological changes were more pronounced. Single-dose and multidose drug treatment had a similar effect on the antioxidant enzymes and MDA, but testicular damage was relatively severe at 15 and 30 days after multidose treatment. By 60 days of treatment withdrawal, however, the above parameters recovered to control levels. The results show that quinestrol causes reversible damage to gerbil testes that might be caused by the oxidative stress and that multidose treatment has more effects on testicular damage compared with one-dose treatment. PMID- 22041278 TI - Moderate ethanol ingestion and cardiovascular protection: from epidemiologic associations to cellular mechanisms. AB - While ethanol intake at high levels (3-4 or more drinks), either in acute (occasional binge drinking) or chronic (daily) settings, increases the risk for myocardial infarction and stroke, an inverse relationship between regular consumption of alcoholic beverages at light to moderate levels (1-2 drinks per day) and cardiovascular risk has been consistently noted in a large number of epidemiologic studies. Although initially attributed to polyphenolic antioxidants in red wine, subsequent work has established that the ethanol component contributes to the beneficial effects associated with moderate intake of alcoholic beverages regardless of type (red versus white wine, beer, spirits). Concerns have been raised with regard to interpretation of epidemiologic evidence for this association including heterogeneity of the reference groups examined in many studies, different lifestyles of moderate drinkers versus abstainers, and favorable risk profiles in moderate drinkers. However, better controlled epidemiologic studies and especially work conducted in animal models and cell culture systems have substantiated this association and clearly established a cause and effect relationship between alcohol consumption and reductions in tissue injury induced by ischemia/reperfusion (I/R), respectively. The aims of this review are to summarize the epidemiologic evidence supporting the effectiveness of ethanol ingestion in reducing the likelihood of adverse cardiovascular events such as myocardial infarction and ischemic stroke, even in patients with co-existing risk factors, to discuss the ideal quantities, drinking patterns, and types of alcoholic beverages that confer protective effects in the cardiovascular system, and to review the findings of recent experimental studies directed at uncovering the mechanisms that underlie the cardiovascular protective effects of antecedent ethanol ingestion. Mechanistic interrogation of the signaling pathways invoked by antecedent ethanol ingestion may point the way towards development of new therapeutic approaches that mimic the powerful protective effects of socially relevant alcohol intake to limit I/R injury, but minimize the negative psychosocial impact and pathologic outcomes that also accompany consumption of ethanol. PMID- 22041282 TI - Distribution of bone marrow-derived cells in the fracture callus during plate fixation in a green fluorescent protein-chimeric mouse model. AB - To clarify the distribution of bone-marrow-derived cells in fractures treated by plate fixation, fracture models were created using the green fluorescent protein (GFP) chimeric mouse. We observed 2 types of fracture healing processes with different types of callus formation and cellular events by using Mouse FixTM, a device allowing plate fixation on the mouse femur, and differences in the distribution of bone-marrow-derived cells between the 2 types. The GFP chimeric mice were created by bone marrow transplantation. Fractures were created on the left femurs of mice and stabilized with either rigid (Group R) or flexible (Group F) plates to prepare undecalcified fresh-frozen sections. In Group F, a large external callus and a large intramedullary callus were formed mostly by endochondral ossification. The cells that made up the intramedullary callus and callus in the fracture gap were GFP positive, but most cells of the external callus were not. In Group R, bone union was achieved mostly without external callus formation, bone apposition occurred directly in the gap, and a small intramedullary callus was formed. As observed in Group F, this group had GFP positive cells in the callus within the fracture gap and in the intramedullary calluses. The results of this study provided direct evidence of the distribution of bone-marrow-derived cells in the callus of fractures treated by plate fixation under different stability conditions. PMID- 22041283 TI - Pathogenicity of Pasteurella pneumotropica in immunodeficient NOD/ShiJic-scid/Jcl and immunocompetent Crlj:CD1 (ICR) mice. AB - Pasteurella pneumotropica is an opportunistic pathogen in rodents. Natural infection in immunodeficient animals suggests that immunodeficiency is a major factor in P. pneumotropica pathogenesis. To understand this process, we performed clinical, pathological and bacteriological studies of immunodeficient NOD/ShiJic scid/Jcl and immunocompetent Crlj:CD1 (ICR) mice experimentally infected with P. pneumotropica ATCC 35149. From 14 days postinoculation, some of P. pneumotropica infected NOD/ShiJic-scid/Jcl mice developed clinical signs of weight loss. Three of 10 P. pneumotropica-infected NOD/ShiJic-scid/Jcl mice developed clinical signs of depression, ruffled coat, and weight loss and died at 27, 34, and 59 days postinoculation. At 35 days postinoculation, almost all P. pneumotropica-infected NOD/ShiJic-scid/Jcl mice had lung abscesses. The bacteria were isolated from the upper and lower respiratory tracts, including the lungs, and blood. In contrast, P. pneumotropica-infected ICR mice exhibited no clinical signs or lesions. The bacteria were isolated from the upper, but not the lower respiratory tracts. We developed an animal model for understanding host interactions with P. pneumotropica. PMID- 22041284 TI - Phenotypic and functional characterization of freshly isolated and expanded canine regulatory T cells. AB - Regulatory T cells (T(reg)) are CD4(+) T lymphocytes with constitutive expression of CD25 and FOXP3, as well as the ability to modulate cellular immune responses. In this study, the phenotypic characteristics, function and feasibility of enrichment and expansion of canine T(reg) were examined. Canine peripheral blood mononuclear cells were isolated and enriched by labelling of CD25, and expansion of T(reg) was achieved by adding interleukin (IL)-2 for 1 week. Phenotypic and functional analyses of T(reg) were performed prior to and after expansion. Canine T(reg) could be phenotypically characterized by CD4, CD25, and FOXP3 expression. Isolation and enrichment of canine T(reg) is possible, but high purities are difficult to achieve without significant cell loss. Expansion of canine T(reg) was possible by adding IL-2 without other growth factors. Higher initial cell numbers seeded allow more substantial T(reg) expansion in vitro. Canine T(reg) have the potential to suppress proliferation of effector T cells (T(eff)). By adding expanded T(reg), a higher capability for suppressing T(eff) could be shown in comparison with freshly isolated T(reg). Enrichment and expansion of canine T(reg) is feasible, and canine T(reg) had similar characteristics to T(reg) from other species. PMID- 22041285 TI - Effect of three types of mixed anesthetic agents alternate to ketamine in mice. AB - Ketamine is usually used for murine anesthesia in animal experiments with other anesthetics for its sedation and analgesic effects. However, ketamine was categorized as a narcotic drug in Japan on January 1, 2007. After this act came into effect, a narcotic handling license became necessary for using and possessing ketamine. Pentobarbital sodium, which is also used for laboratory animal experiments as Nembutal, is no longer being manufactured. For these reasons, other anesthetic agents that can be used without a license are needed. In this paper, we examined the use of anesthetics other than ketamine and pentobarbital sodium. A combination anesthetic (M/M/B: 0.3/4/5) was prepared with 0.3 mg/kg of medetomidine, 4.0 mg/kg of midazolam, and 5.0 mg/kg of butorphanol. The anesthetics were administered to male ICR mice by intraperitoneal injection. In order to assess anesthetic depth and duration, we stimulated the mice directly after loss of righting reflexes to recovery of these same reflexes and then recorded four parameters--a tail pinch reflex, a pedal withdrawal reflex in the forelimbs, a pedal withdrawal reflex in the hindlimbs, and corneal reflex. Each parameter was scored, and the anesthetic depth, expressed by the total score, was summed. The surgical anesthesia duration of M/M/B: 0.3/4/5 mg/kg was almost identical to the surgical anesthetic duration with a ketamine and xylazine mixture (80-8 mg/kg). These data suggested that mice can be anesthetized by M/M/B: 0.3/4/5 as an alternate to ketamine. We thus can recommend M/M/B: 0.3/4/5 for murine surgical anesthesia. PMID- 22041286 TI - Effects of quinestrol as a contraceptive in mongolian gerbils (Meriones unguiculatus). AB - The contraceptive effects of quinestrol in Mongolian gerbils were examined. The results showed that body weight significantly increased after quinestrol treatment, except in the group that received the highest dose. The gonadosomatic index of ovaries decreased, whereas that of uteri increased, and uterine edema appeared after quinestrol treatment. Histological examination revealed that the ovaries had a lack of mature follicles and corpora lutea and that the myometrium and endometrium of the uteri became thin after quinestrol treatment. Persistent estrous appeared after quinestrol treatment, and time to persistent estrous shortened with increasing doses of quinestrol. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels decreased, whereas estradiol (E2) and progesterone (P4) levels increased after quinestrol treatment, and the effects were dose-dependent. During gestation, the serum E2 levels in the different treatment groups were not significantly different. During gestation in the control groups, the serum P4 levels from days 0 to 15 were higher than in the quinestrol-treated groups; however, they did not show significant differences from days 18 to 24. Doses of 0.1 to 2.7 ug/g quinestrol over 6 days completely inhibited fertility. Birth time was prolonged with increasing doses of quinestrol. The findings suggest that quinestrol has marked estrogenic effects in Mongolian gerbils and may inhibit follicle maturation and ovulation through lowered gonadotropin levels. Uterine edema and abnormal E2 and P4 levels during gestation are important causes of pregnancy failure in quinestrol-treated Mongolian gerbils. Quinestrol causes prolonged inhibition of fertility in Mongolian gerbils. PMID- 22041287 TI - Vinyl isolator breeding induces insulin resistance in C57BL/6JJcl mice. AB - As basic probiotics studies, the glucose tolerance test (GTT), insulin tolerance test (ITT), and adipokine and hepatic enzyme activities were investigated in male C57BL/6JJcl (B6J) mice under germfree (GF) or specific pathogen free (SPF) conditions. GF B6J mice were reproduced by reproductive engineering and cesarean section using a vinyl isolators (GF group). Some GF group mice were transferred to other vinyl isolators under SPF conditions (SPF group). In addition, conventional B6J mice bred in an open room were defined as controls (Conv group). GTT, ITT, and the sampling of blood, liver, white adipose tissue, and pancreas were performed when these B6J mice were at the age of 8 weeks. As a result, the GF and SPF groups showed hyperglycemia, impaired glucose tolerance and insulin resistance when compared with the Conv group. The adipose tissues and plasma TNFalpha concentrations in the GF and SPF groups were enlarged and increased when compared with the Conv group. Hepatic enzyme activities associated with glucose uptake in the GF and SPF groups were higher than those in the Conv group. However, hepatic enzyme activities associated with gluconeogenesis in the GF and SPF groups were lower than those in the Conv group. We assumed that these results were reactions by the liver to recover from the impaired glucose tolerance and the insulin resistance caused by vinyl isolator breeding of the GF and SPF groups by control of glucose metabolism. PMID- 22041288 TI - Endocrinological differences between Hatano high- and low-avoidance rats during early two-way avoidance acquisition. AB - Hatano high (HAA)- and low (LAA)-avoidance rats were selected from Sprague-Dawley rats genetically on the basis of their active avoidance behavior in a shuttle-box test. The purpose of this study was to investigate stress-related alterations of hormones corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP), prolactin, and adrenocorticotropin (ACTH) in the brain and blood during early avoidance acquisition using two lines of Hatano rats. In paraventricular nucleus (PVN) of the hypothalamus, the CRH levels in HAA rats were significantly increased after shuttle-box tasks compared with before the tasks, whereas the CRH levels in LAA rats significantly decreased after shuttle-box tasks compared with before the tasks. In the HAA rats, the CRH and AVP levels in the median eminence decreased after shuttle-box tasks, whereas there were no significant differences in the levels between before and after shuttle-box tasks in LAA rats. The plasma concentrations of ACTH were significantly higher in HAA rats than in LAA rats after shuttle-box tasks. These results show that the response of CRH-ACTH was higher in HAA rats than in LAA rats. This phenotype may be an important reason for the high avoidance rates of shuttle-box tasks in HAA rats. These endocrine differences in early avoidance acquisition may be involved in regulation of their avoidance responses in the shuttle-box task. PMID- 22041290 TI - Environmental contamination because of multidrug-resistant Acinetobacter baumannii surrounding colonized or infected patients. AB - BACKGROUND: Multidrug-resistant (MDR) Acinetobacter baumannii (MDR-AB) is an important nosocomial pathogen associated with significant morbidity and mortality. METHODS: We conducted a prospective cohort study of intensive care unit patients colonized or infected with MDR-AB at a tertiary care hospital from October 2008 to January 2009. For each patient, 10 surfaces in the patient room were sampled and evaluated for the presence of A baumannii. Pulsed-field gel electrophoresis was performed on all environmental isolates and a clinical isolate if available. RESULTS: Fifty rooms were sampled; 48% (24/50) were positive at 1 or more environmental sites. Supply carts (10/50, 20%), floors (8/50, 16%), infusion pumps (7/50, 14%), and ventilator touch pads (5/44, 11.4%) were most commonly contaminated. Patients with a recent history of MDR-AB were no more likely to contaminate their environment than patients with a remote history (51% vs 36%, respectively, P value = .50). In 85% (17/20) of cases, the environmental isolate was classified as genetically similar to the patient isolate. CONCLUSION: For patients with MDR-AB, the surrounding environment is frequently contaminated, even among patients with a remote history of MDR-AB. Surfaces often touched by health care workers during routine patient care are commonly contaminated and may be a source of nosocomial spread. PMID- 22041292 TI - Memory in paediatric temporal lobe epilepsy: effects of lesion type and side. AB - This study investigated the role of underlying pathology on memory function of children with temporal lobe epilepsy (TLE). Memory was assessed in 44 children with TLE resulting from hippocampal sclerosis (HS) or dysembryoplastic neuroepithelial tumours (DNT), and 22 control children. Delayed story and paired associate recall performance was significantly more impaired in children with HS compared to those with DNT, irrespective of the affected side. Semantic memory was impaired in both HS groups, and also in the left DNT group. These results suggest a role for type, and to a lesser extent, side of pathology in the memory profile of children with TLE. PMID- 22041291 TI - Smooth muscle and other cell sources for human blood vessel engineering. AB - Despite substantial progress in the field of vascular tissue engineering over the past decades, transition to human models has been rather challenging. The limited replicative life spans of human adult vascular cells, and their slow rate of collagenous matrix production in vitro, have posed important hurdles in the development of mechanically robust and biologically functional engineered grafts. With the more recent advances in the field of stem cells, investigators now have access to a plethora of new cell source alternatives for vascular engineering. In this paper, we review various alternative cell sources made available more recently for blood vessel engineering and also present some recent data on the derivation of smooth muscle cells from human induced pluripotent stem cells. PMID- 22041293 TI - Predicting miRNA-mediated gene silencing mode based on miRNA-target duplex features. AB - There are two main mechanisms of miRNA-mediated gene silencing: either mRNA degradation or translational repression. However, the precise mechanism of target mRNAs regulated by miRNA remains unclear. As a complementary approach to experiment, a computational method was proposed to recognize the mechanism of miRNA-mediated gene silencing in human. We have analyzed extensive features correlated with miRNA-mediated silencing mechanism of mRNA. It is found that, the duplex structure, the number of binding sites and the structural accessibility of target site region are effective factors in determining whether a target mRNA is cleaved or only translationally inhibited. An SVM-based classifier was constructed to predict the regulation mode of miRNA based on these informative features. The results indicated that the approach proposed is effective in distinguishing whether a target mRNA is cleaved or translationally inhibited in human. Furthermore, the web server microDoR (http://reprod.njmu.edu.cn/microdor) has been developed and is freely available for users. PMID- 22041294 TI - Immunohistochemical detection of meconium in the fetal membrane, placenta and umbilical cord. AB - OBJECTIVE: To develop the immunohistochemistry specific for meconium in the placenta, fetal membrane and umbilical cord. STUDY DESIGN: We previously reported the specific presence of zinc coproporphyrin I (ZnCP-I) in human meconium and demonstrated the possible diagnostic use of an elevation in maternal plasma ZnCP I levels in cases of amniotic fluid embolism. In this study, we developed a new specific monoclonal antibody for ZnCP-I and applied it to the immunostaining of meconium in the placenta, fetal membrane, and umbilical cord. RESULTS: Immunoreactivity of ZnCP-I clearly and specifically identified meconium in the placenta, fetal membrane, and umbilical cord. It was especially useful in cases of severe chorioamnionitis to detect meconium in the macrophages surrounded by numerous neutrophils. In more than half of the cases, meconium was detected in clear amniotic fluid at delivery, suggesting previous exposure. CONCLUSIONS: Immunohistochemical detection of ZnCP-I is a highly sensitive histological diagnosis of meconium. PMID- 22041296 TI - Glucocorticoids mediate stress-induced priming of microglial pro-inflammatory responses. AB - Acute and chronic stress sensitizes or "primes" the neuroinflammatory response to a subsequent pro-inflammatory challenge. While prior evidence shows that glucocorticoids (GCs) play a pivotal role in stress-induced potentiation of neuroinflammatory responses, it remains unclear whether stress-induced GCs sensitize the response of key CNS immune substrates (i.e. microglia) to pro inflammatory stimuli. An ex vivo approach was used to address this question. Here, stress-induced GC signaling was manipulated in vivo and hippocampal microglia challenged with the pro-inflammatory stimulus LPS ex vivo. Male Sprague Dawley rats were either pretreated in vivo with the GC receptor antagonist RU486 or adrenalectomized (ADX). Animals were then exposed to an acute stressor (inescapable tailshock; IS) and 24 h later hippocampal microglia were isolated and challenged with LPS to probe for stress-induced sensitization of pro inflammatory responses. Prior exposure to IS resulted in a potentiated pro inflammatory cytokine response (e.g. IL-1beta gene expression) to LPS in isolated microglia. Treatment in vivo with RU486 and ADX inhibited or completely blocked this IS-induced sensitization of the microglial pro-inflammatory response. The present results suggest that stress-induced GCs function to sensitize the microglial pro-inflammatory response (IL-1beta, IL-6, NFkappaBIalpha) to immunologic challenges. PMID- 22041297 TI - CD200 fusion protein decreases microglial activation in the hippocampus of aged rats. AB - The glycoprotein, CD200, is primarily expressed on neurons and its cognate receptor CD200R is expressed principally on cells of the myeloid lineage, including microglia. The interaction of CD200 with its receptor plays a significant role in maintaining microglia in a quiescent state and therefore a decrease in CD200 expression in brain is associated with evidence of microglial activation. Conversely, activation of CD200R, for example using a CD200 fusion protein (CD200Fc), should result in a decrease in microglial activation. Here we assessed the effect of delivery of CD200Fc intrahippocampally on microglial activation and on long-term potentiation (LTP) in perforant path-granule cell synapses in young and aged rats. We hypothesized that the age-related changes in microglial activation would be attenuated by CD200Fc resulting in an improved ability of aged rats to sustain LTP. The data indicate that expression of markers of microglial activation including major histocompatibility complex Class II (MHCII) and CD40 mRNA, as well as MHCII immunoreactivity, were increased in hippocampus of aged, compared with young, rats and that these changes were associated with a deficit in LTP; these changes were attenuated in hippocampal tissue prepared from aged rats which received CD200Fc. Microglial activation and a deficit in LTP have also been reported in lipopolysaccharide (LPS)-treated rats and, here, we report that these changes were also attenuated in CD200Fc-treated animals. Thus the negative impact of microglial activation on the ability of aged and LPS-treated rats to sustain LTP is ameliorated when CD200R is activated by CD200Fc. PMID- 22041298 TI - A comparative study of color quenching correction methods for Cerenkov counting. AB - The color quenching correction for Cerenkov counting is normally based on indexes defined for liquid scintillation spectra. Because of the differences in the spectrum shapes, these indexes are not optimal, and a different method was proposed based on the integral counting of the external (152)Eu source spectra of a 1200 Quantulus system. We have shown that this method, named ESAR (external source area ratio), is superior to all the other correction methods, offering the highest sensitivity and the widest range of application. PMID- 22041299 TI - Cross sections of the 36Ar(d,alpha)34mCl, 40Ar(d,alpha)38Cl, and 40Ar(d,p)41Ar nuclear reactions below 8.4 MeV. AB - We have measured the cross section for production of the medically interesting isotope (34m)Cl, along with (38)Cl and (41)Ar, using deuteron bombardments of (36)Ar and (40)Ar below 8.4 MeV. ALICE/ASH analytical codes were employed to determine the shape of nuclear excitation functions, and experiments were performed using the University of Wisconsin tandem electrostatic accelerator to irradiate thin targets of argon gas. PMID- 22041300 TI - New neutralizing antibody epitopes in hepatitis C virus envelope glycoproteins are revealed by dissecting peptide recognition profiles. AB - One of the greatest challenges to HCV vaccine development is the induction of effective immune responses using recombinant proteins or vectors. In order to better understand which vaccine-induced antibodies contribute to neutralization of HCV the quality of polyclonal anti-E1E2 antibody responses in immunized mice and chimpanzees was assessed at the level of epitope recognition using peptide scanning and neutralization of chimeric 1a/2a, 1b/2a and 2a HCVcc after blocking or affinity elution of specific antibodies. Mice and chimpanzees were immunized with genotype 1a (H77) HCV gpE1E2; all samples contained cross-neutralizing antibody against HCVcc. By functionally dissecting the polyclonal immune responses we identified three new regions important for neutralization within E1 (aa264-318) and E2 (aa448-483 and aa496-515) of the HCV glycoproteins, the third of which (aa496-515) is highly conserved (85-95%) amongst genotypes. Antibodies to aa496-515 were isolated by affinity binding and elution from the serum of a vaccinated chimpanzee and found to specifically neutralize chimeric 1a/2a, 1b/2a and 2a HCVcc. IC50 titres (IgG ng/mL) for the aa496-515 eluate were calculated as 142.1, 239.37 and 487.62 against 1a/2a, 1b/2a and 2a HCVcc, respectively. Further analysis demonstrated that although antibody to this new, conserved neutralization epitope is efficiently induced with recombinant proteins in mice and chimpanzees; it is poorly induced during natural infection in patients and chimpanzees (7 out of 68 samples positive) suggesting the epitope is poorly presented to the immune system in the context of the viral particle. These findings have important implications for the development of HCV vaccines and strategies designed to protect against heterologous viruses. The data also suggest that recombinant or synthetic antigens may be more efficient at inducing neutralizing antibodies to certain epitopes and that screening virally infected patients may not be the best approach for finding new cross-reactive epitopes. PMID- 22041301 TI - When an aluminium adjuvant is not an aluminium adjuvant used in human vaccination programmes. PMID- 22041303 TI - Immunological Correlates of Vaccine-Derived Protection Fondation Merieux Conference Center 'Les Pensieres' Veyrier-Du-Lac, France, Sept. 20-22, 2010. PMID- 22041302 TI - Vaccination by delayed treatment of infection. AB - Two medical interventions allow us to combat infectious diseases: vaccination which can be administered well in advance of exposure, and antimicrobials which are most often administered contemporaneously with exposure. In this paper we show how they can, in principle, be combined - with infection followed by treatment being used as a form of vaccination. We use mathematical models to examine how appropriately administered antimicrobial treatment following natural infection can be used to reduce the pathology caused by the infection, and also generate long-lasting immunological memory to the pathogen. The models explore the tradeoff between reduction in pathology and strength of immunization. This tradeoff suggests a limited treatment window during which antimicrobial treatment can be started and provide both amelioration of disease symptoms and long-term immunity. This approach may be particularly well suited to combat the emergence of novel pandemic influenza infections particularly for individuals such as medical healthcare professionals at greatest risk for exposure during the initial stages of a pandemic. PMID- 22041304 TI - The influence of the stigma of obesity on H1N1 influenza vaccine sequencing in Canada in 2009. AB - In 2009, the Public Health Agency of Canada (PHAC) provided guidelines about which groups should be given first access to the H1N1 influenza vaccine. These guidelines recommended that people under 65 with chronic health conditions should be among the first groups to receive the H1N1 influenza vaccine. Severe obesity was among the relevant chronic health conditions identified by PHAC. Since health care is under the jurisdiction of the ten Canadian provinces, the provinces were not required to follow these recommendations in their respective mass vaccination campaigns. Only one province (Manitoba) followed the PHAC recommendations with respect to severe obesity. Four provinces did not offer early vaccination to this group. Other provinces listed severe obesity as a sequencing category late in the vaccination campaign or placed narrow age restrictions on those who were given early access. This commentary argues that the Canadian provinces demonstrated an ambiguous commitment to the early vaccination of people who were severely obese, and that there is evidence that the stigma of obesity influenced H1N1 influenza vaccine sequencing decisions in many Canadian provinces. PMID- 22041306 TI - Effect of individual and neighborhood socioeconomic status on oral cancer survival. AB - This population-based study investigated the relationship between individual and neighborhood socioeconomic status (SES) and oral cancer mortality. A population based follow-up study was conducted of 3607 oral cancer patients (predominantly male) who were diagnosed between 2004 and 2005. Each patient was traced to death or for 2 years. Individual SES was defined by enrollee category. Neighborhood SES was defined by income, and numbers of doctors, and neighborhoods were grouped into advantaged and disadvantaged areas. The Cox proportional hazards model was used to compare the death-free survival rate between the different SES groups after adjusting for possible confounding and risk factors. In oral cancer patients aged below 65 years, death rates among those with low SES were highest in disadvantaged neighborhoods. After adjusting for patient characteristics (age, gender, Charlson Comorbidity Index Score, urbanization, and area of residence), tumor extent, treatment modalities (operation, adjuvant therapy), hospital characteristics (ownership, teaching level, caseload), and year of diagnosis, oral cancer patients with low individual SES in disadvantaged neighborhoods conferred a 1.46- to 1.64-fold higher risk for death, compared with patients with high individual SES in advantaged neighborhoods. No statistically significant difference was found in risk of death between different SES groups in patients aged 65 and above. Our findings indicate that oral cancer patients with low individual SES have the highest risk of mortality even under a universal health care system. Public health strategies and welfare policies must continue to focus on this vulnerable group. PMID- 22041305 TI - TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4+ memory T cell loss in SIVmac251-challenged rhesus macaques. AB - Adjuvant plays an important role in increasing and directing vaccine-induced immune responses. In a previous study, we found that a mucosal SIV vaccine using a combination of IL-15 and TLR agonists as adjuvant mediated partial protection against SIVmac251 rectal challenge, whereas neither IL-15 nor TLR agonists alone as an adjuvant impacted the plasma viral loads. In this study, dissociation of CD4(+) T cell preservation with viral loads was observed in the animals vaccinated with adjuvants. Significantly higher levels of memory CD4(+) T cell numbers were preserved after SIVmac251 infection in the colons of the animals vaccinated with vaccine containing any of these adjuvants compared to no adjuvant. When we measured the viral-specific CD8(+) tetramer responses in the colon lamina propria, we found significantly higher levels of gag, tat, and pol epitope tetramer(+) T cell responses in these animals compared to ones without adjuvant, even if some of the animals had similarly high viral loads. Furthermore, this CD4(+) T preservation was positively correlated with increased levels of gag and Tat, but not pol tetramer(+) T cell responses, and inversely correlated with beta-chemokine expression. The pre-challenged APOBEC3G expression level, which has previously been shown inversely associated with viral loads, was further found positively correlated with CD4(+) T cell number preservation. Overall, these data highlight one unrecognized role of adjuvant in HIV vaccine development, and show that vaccines can produce a surprising discordance between CD4(+) T cell levels and SIV viral load. PMID- 22041307 TI - Immunological fecal occult blood test vs. serum ferritin for detection of colorectal neoplasia in high risk asymptomatic population. AB - INTRODUCTION: Fecal occult blood tests (FOBT) (biochemical or immunological) are based on the fact that most of the polyps or cancers bleed. Anemia due to iron deficiency is a wellknown sign for colorectal cancer (CRC). Ferritin is frequently used to select candidates for colonoscopy. OBJECTIVE: To determine and compare the diagnostic value of immunological fecal occult blood test vs. ferritin for the detection of colorectal neoplasia (cancer or polyps) in high risk patients. METHODS: A transversal prospective study at National Cancer Institute, Mexico City, in consecutive asymptomatic subjects at high risk for CRC was performed, comparing two tests (immunological against serum ferritin) with colonoscopy plus histopathology. Both tests were performed in a blindly fashion previous to colonoscopy. RESULTS: Fifty patients were included in the study; twenty-eight patients had colorectal neoplasia (21 CRC, 7 adenomas). All immunologic tests for fecaloccult blood were positive in patients with colorectal lesions (sensitivity, 98%). There was no difference between the mean ferritin levels in patients with CRC or adenomas vs. those with negative colonoscopy (p = 0.58). The cutoff point where significant relationship between serum ferritin levels and colon lesions was established was ?46 ng/mL. In anemic patients with serum ferritin levels <46 ng/mL, the test had a sensitivity 53%, specificity 86%, positive predictive value 83%, and negative predictive value of 59% (p = 0.003). CONCLUSIONS: The immunological FOBT is a better diagnostic tool than serum ferritin for screening of colonic neoplasms. PMID- 22041308 TI - [Esophageal motor disorders in asymptomatic subjects with Trypanosoma cruzi infection]. AB - BACKGROUND: The indeterminate chronic or "asymptomatic" phase of Trypanosoma cruzi (Chagas' disease) infection is characterized by the absence of gastrointestinal symptoms, and has an estimated duration of 20 to 30 years. However, the intramural denervation that induces dysfunction of the gastrointestinal tract is progressive. Recently, epidemiological studies have shown that the seroprevalence for this infection in our area ranges between 2% and 3% of the population. OBJECTIVE: To detect the presence of esophageal motor disorders in asymptomatic individuals chronically infected with Trypanosoma cruzi using standard esophageal manometry. METHODS: A cross sectional study in 28 asymptomatic subjects (27 men, age 40.39 +/- 10.79) with serological evidence of infection with Trypanosoma cruzi was performed. In all cases demographic characteristics, gastrointestinal symptoms and esophageal motility disorders using conventional manometry were analyzed. RESULTS: In this study 54% (n = 15) of asymptomatic subjects had an esophageal motor disorder: 5 (18%) had nutcracker esophagus, 5 (18%) nonspecific esophageal motor disorders, 3 (11%) hypertensive lower esophageal sphincter (LES), 1 (4%) an incomplete relaxation of the LES and 1 (4%) had chagasic achalasia. CONCLUSIONS: More than half of patients that course with Chagas' disease in the indeterminate phase and that are apparently asymptomatic have impaired esophageal motility. Presence of hypertensive LES raises the possibility that this alteration represents an early stage in the development of chagasic achalasia. PMID- 22041309 TI - The importance of socioeconomic factors in symptoms of heartburn. AB - INTRODUCTION: Patients' socioeconomic status is rarely assessed during medical consultations. OBJECTIVE: To correlate patients' socioeconomic conditions with symptoms of heartburn. METHODS: 1184 patients who answered a questionnaire in three cities on the coast of the State of Sa Paulo, Brazil, were evaluated prospectively. Socioeconomic status was assessed using several criteria: number of bathrooms, consumer goods present at home, health conditions at home, comfort (cars and/or home helps), monthly family income and head of household's educational level. RESULTS: 583 patients (49.2%) reported occurrences of heartburn over the 30 days preceding the consultation, with frequencies ranging from five to thirty episodes over this period. Among patients from the city of Guaruja (low socioeconomic condition), 9.7% had never felt heartburn, while 65.7% reported occurrences, reaching statistical significance in relation to patients of medium socioeconomic condition (city of Sa Vicente) (p = 0.012). There was no difference between patients from medium socioeconomic condition and patients from Santos (high socioeconomic condition) (p = 0.997). There was a statistically significant difference in occurrence of heartburn between the patients with high socioeconomic condition and those of low socioeconomic condition (p = 0.002). CONCLUSIONS: The least favored socioeconomic status patients, as confirmed according to a variety of socioeconomic factors, presented greater incidence of heartburn than did the most favored social class. PMID- 22041310 TI - [IT-Knife-2 electroincision as primary treatment of anastomotic strictures]. AB - BACKGROUND: Dysphagia is a common problem after surgical stenosis (5% to 55%) and can be refractory to conventional endoscopic treatment in 22% of cases. It has been proposed that electro-incision is an alternative and effective treatment. OBJECTIVE: To evaluate the effectiveness of electro-incision with the insulation tipped diathermic Knife-2 (IT-Knife-2) in the treatment of dysphagia produced by surgical anastomotic strictures. METHODS: Longitudinal and case-series study from August 2009 to June 2010. Eight consecutive patients with anastomotic stricture associated dysphagia and naive to endoscopic treatment were included. We performed three or more radiated cuts in the stricture until passage of the gastroscope was achieved with IT-Knife-2 and electrocautery (ERBE IC 200) with a 70-100 W energy cut-off and 25 W coagulation. We carried out measurements at baseline and 15 days after the intervention, evaluating the dysphagia by the Atkinson grading scale and endoscopic changes. RESULTS: The majority of patients were at clinical stage IV with an Eastern Cooperative Oncology Group score of 1 - 3 and Karnofsky between 40 and 90. At the time of endoscopic diagnosis, patients had dysphagia grade II and III. Strictures in all of the cases were short in length and had a diameter of minor than 5 mm. At 15 days of the intervention, no patient demonstrated dysphagia (p = 0.0013) and the anastomotic diameters was more than 9.5 mm and without evidence of stenosis (p = 0.0001). None of our patients presented postincisional complications. CONCLUSIONS: Electro-incision with IT-Knife-2 is effective as primary treatment for the relief of benign dysphagia associated with postsurgical anastomotic stenosis." PMID- 22041312 TI - Clinical and manometric findings on elderly patients with achalasia. AB - INTRODUCTION: Data regarding the age impact on the clinical presentation and esophageal motility in adults with idiopathic achalasia are scarce. OBJECTIVE: To asses the clinical and manometric features of elderly patients with idiopathic achalasia. METHODS: The medical charts of 159 patients diagnosed with achalasia were divided into two groups according to the patients' age: ?60 years (n = 123) and >60 years (n = 36). Clinical and manometric findings [esophageal body aperistalsis, basal lower esophageal sphincter (LES) pressure and abnormal LES relaxation] of both groups were compared upon diagnosis. Patients with previous esophageal interventions were excluded. RESULTS: Only chest pain was more common in the ?60 year-old group (51.2% vs. 22.2%, p <0.003). This difference remained when comparing the group of men <=60 years. Other presenting features (including sex, weight loss, and presence of dysphagia, regurgitation and heartburn) did not differ between the groups. The LES relaxation was incomplete in 70.4% of the cases. No differences on the basal LES pressure, residual LES pressure or the amplitude of the esophageal body contractions between both groups were found. Considering only the classic achalasia cases, symptomatic time before diagnosis was greater in <=60 years compared with older patients: 24 vs. 12 months (p <0.05), respectively. CONCLUSIONS: These results suggest that chest pain is more common in younger male achalasia patients and residual LES pressure decreases with age. PMID- 22041311 TI - [The value of targeted biopsies with endoscopic magnification and narrow band image vs. chromoendoscopy for the diagnosis of gastric metaplasia]. AB - INTRODUCTION: Endoscopy is the better test to detect premalignant lesions, but its main problem is the sampling error. OBJECTIVES: To evaluate the diagnostic usefulness of endoscopic biopsies using narrow band imaging (NBI) vs. chromoendoscopy for diagnosing gastric intestinal metaplasia. METHODS: Forty one patients were studied with conventional endoscopy, NBI magnification endoscopy and chromoendoscopy (3% acetic acid, 0.6% indigo carmine) for examination of gastric antrum. Biopsies were taken randomly from the antrum, body and incisura angularis. Additional biopsies were taken from areas with villous or crypt pattern according to NBI and chromoendoscopy examination (targeted biopsies). RESULTS: 240 biopsies were taken, 205 randomized biopsies and 35 targeted biopsies. Intestinal metaplasia was found in 25 randomized biopsies and 9 directed samples (12% vs. 25.7%). The NBI and chromoendoscopy had sensitivity of 70% vs. 77%, specificity of 97% vs. 98%, with diagnostic accuracy of 96% vs. 97%, respectively. Random biopsies and targeted biopsies had a sensitivity of 91% vs. 74%, specificity of 51% vs. 95%, and diagnostic accuracy of 93% vs. 86%, respectively. The intra-observer variability showed a k value of 0.86 (range 0.74 to 0.99). CONCLUSION: Targeted biopsies are more specific than random biopsies to detect gastric intestinal metaplasia. NBI and chromoendoscopy may be used similarly to guide biopsies. PMID- 22041313 TI - [If no-acid, no-heartburn? New physiopathological mechanisms of the gastroesophageal reflux disease]. AB - The role of acid is very well established in the pathogenesis of gastroesophageal reflux disease (GERD). In the current era of frequent use of proton pump inhibitors, we are seeing increasing numbers of patients with symptoms that are refractory to acid suppression. Recent studies suggest that in patients being treated with proton pump inhibitors, non-acid reflux (composed of buffered gastric contents), esophageal hypersensitivity, esophageal motor dysfunction and psychological comorbidity can cause persistent symptoms. Concepts surrounding possible pathogenetic mechanisms leading to heartburn as a result of nonacid reflux and other mechanisms are explored, and potential treatments for this type of reflux are outlined in this review. PMID- 22041314 TI - [Laparoscopic low anterior resection for rectal endometriosis]. PMID- 22041315 TI - [Esophageal squamous papilloma: an uncommon endoscopic finding]. PMID- 22041316 TI - [Dystrophic osseus metaplasia on small bowell mesentery in a patient with multiple abdominal sugeries: a case report]. AB - Heteropropic ossification was initially described by Riedel in 1883. This is a rare disease but well documented in gastrointestinal tract. Several mechanisms have been proposed to determine the etiology of this metaplasia. We present a 59 year old male that was treated in the National Institute of Medicine Sciences and Nutrition Salvador Zubiran in whom after various abdominal surgical procedures the presence of bowel osseous metaplasia was documented. PMID- 22041317 TI - [Case report: laparoscopic cholecystectomy and common bile duct exploration in a 60 year-old patient with situs inversus]. AB - This is a case report of a 60 year-old male patient with acute cholecystitis and jaundice, unaware of having situs inversus. Patient underwent successfully laparoscopic cholecystectomy with bile duct exploration in spite of the unusual clinical situation. A literature review using Pubmed database, since 1989, in Spanish and English literature was performed. We found only two reports of cholecystectomy and common bile duct exploration in patients with situs inversus. This is the first case reported in our country. PMID- 22041318 TI - [Gastric duplication in adults: a case report and literature review]. AB - Duplications of the gastrointestinal tract are a rare congenital malformations that usually presents in the first 2 years of life with symptoms of poor weight gain and abdominal palpable mass. The present is a case report of 41 year-old woman who was evaluated for upper abdominal pain. Upper endoscopy revealed a submucosal mass in the greater curvature of the stomach with initial suspect diagnosis of gastrointestinal stromal tumor. Endoscopic ultrasound confirmed partially cystic submucosal mass which was removed with a distal gastric wedge resection without complications. Histopathological report was congenital gastric duplication. PMID- 22041319 TI - Gastric perforation and subarachnoid hemorrhage secondary to intragastric balloon device. AB - Obesity is a major health problem worldwide that leads to high morbidity and mortality rates. Medical options for obesity treatment are multiple and invasive therapy may be classified as surgical and non-surgical. Intragastric balloon device placement is an invasive non-surgical option that may benefit some obese patients. Potential complications related to intragastric balloon placement are multiple and perforations at the esophagus or stomach are the most hazardous. Prompt surgical management is mandatory upon the diagnosis of gastric perforation secondary to intragastric balloon to avoid further complications and mortality. Here we report an unusual case of patient that suffered both a subarachnoid hemorrhage as well as a gastric perforation related to intragastric balloon in which early diagnosis and prompt surgical treatment lead to a successful outcome. PMID- 22041320 TI - Successful endoscopic ultrasound-guided overstenting biliary drainage through a pre-existing proximal migrated metal biliary stent. AB - Biliary endoscopic drainage using metallic self-expanded stents has become a well established method for palliative treatment of malignant biliary obstruction. However, its occlusion, mainly by tumor overgrowth, is still the main complication without a standard treatment. We here describe a new method of treatment for biliary metallic stent occlusion, through the echo guided biliary drainage. We present a 68-year-old patient with metastatic pancreatic cancer previously treated for jaundice with ERCP and self-expandable metallic stent insertion. Four weeks later, the patient developed jaundice and symptoms of gastric outlet obstruction. A new ERCP confirmed obstruction of the second portion of the duodenum, due to diffuse tumor growth. EUS was performed, and the previous metal biliary stent was seen occluded at the distal portion in the common bile duct. A EUS-guided choledocododenostomy was performed and then, an overlapping self-expanding metal enteral stent was placed through the malignant obstruction. There were no early complications and the procedure was also clinically effective in relieving jaundice and gastric outlet obstruction symptoms. If ERCP fails in the management of occluded biliary metallic stents, EUS biliary drain can provide effective biliary decompression and should be considered an alternative to other endoscopic techniques. PMID- 22041321 TI - [Buschke-Lowenstein Tumor associated to nasopharyngeal condillomatosis]. AB - Giant Acuminata Condyloma or Buschke-Lowenstein Tumor (BLT) is a rare disease characterized typically by its perineal location, local aggressiveness and its cauliflower-like aspect. BLT is associated with Human Papilloma Virus (HPV) infection. Because malignant transformation of BLT is high, radical local excision and histopathological examination are needed. We report a 26-year-old male, seropositive for HIV with giant verrucous lesions in the inguinal, perineal, suprapubic and genital area. Rectosismoidoscopy revealed anal canal involvement. Oropharyngeal papillomatosis was also found. Wide local excision was performed, including inguinoperineal and oropharyngeal lesions. Pathology studies show papillomatosis with koilocytes and no evidence of malignant transformation. PMID- 22041322 TI - [Epidermolysis bullosa acquisita complicated by esophageal stenosis. Endoscopic treatment with thermoplastic dilators and intralesional steroid injection]. AB - Epidermolysis bullosa acquisita (EBA) is a rare auto-immune dermatologic disease, produced by auto-antibodies against colagen VII. We report a 44 years old male patient with EBA diagnosed 15 years before, who presented with progressive disphagia, being diagnosed an esophageal involvement of EBA. The patient was submitted to endoscopic treatment with thermoplastic bougie dilation and intralesional corticosteroid injection. The patient improved clinically with recovery of nutritional status. Esophageal involvement in EBA is very rare and its reason is still unknown. Endoscopic approach must be cautiously performed with the use of small diameter endoscopes, small caliber dilators, intralesional injection of corticosteroid and enteral tube in order to minimize the risks of complications, as well as esophageal rest from food trauma and better reparatory molding of the epithelium. PMID- 22041323 TI - Statins do not significantly affect muscle sympathetic nerve activity in humans with nonischemic heart failure: a double-blind placebo-controlled trial. AB - BACKGROUND: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) have been shown to reduce sympathetic nervous system (SNS) activation in experimental heart failure (HF). However, this potential mechanism of action of statins in HF has not been well studied in humans. METHODS AND RESULTS: Twenty-six patients with nonischemic systolic HF (left ventricular ejection fraction [LVEF] <=35%) were randomized to atorvastatin (10 mg) or placebo for 3 months. Pre- and posttreatment testing included echocardiography, laboratory assays, quality of life (QOL) questionnaires, and peroneal nerve muscle sympathetic nerve activity (MSNA) via microneurography. Eighteen subjects had technically adequate MSNA tracings before and after treatment. The cohort was 65% male, 81% New York Heart Association functional class II, LVEF 26 +/- 6%, and low-density lipoprotein cholesterol (LDL-C) 108 +/- 26 mg/dL. Baseline MSNA was 41 +/- 2 bursts/min. LDL C significantly decreased in the atorvastatin (-36.8%) versus the placebo (-0.1%) group (P < .0001). However, there was no significant change in MSNA (-16.2% vs 2.5%), LVEF, B-type natriuretic peptide, or QOL score in the atorvastatin compared with the placebo group. CONCLUSIONS: Short-term statin therapy in patients with nonischemic HF does not result in a significant decrease in SNS activation as measured by MSNA. These findings are consistent with the neutral outcomes of large clinical trials of statins in HF. PMID- 22041324 TI - Assessing health literacy in heart failure patients. AB - BACKGROUND: Health literacy has important implications for health interventions and clinical outcomes. The Shortened Test of Functional Health Literacy in Adults (S-TOFHLA) is a timed test used to assess health literacy in many clinical populations. However, its usefulness in heart failure (HF) patients, many of whom are elderly with compromised cognitive function, is unknown. We investigated the relationship between the S-TOFHLA total score at the recommended 7-minute limit and with no time limit (NTL). METHODS AND RESULTS: We enrolled 612 rural-dwelling adults with HF (mean age 66.0 +/- 13.0 years, 58.8% male). Characteristics affecting health literacy were identified by multiple regression. Percentage of correct scores improved from 71% to 86% (mean percent change 15.1 +/- 18.1%) between the 7-minute and NTL scores. Twenty-seven percent of patients improved >=1 literacy level with NTL scores (P < .001). Demographic variables explained 24.2% and 11.1% of the variance in % correct scores in the 7-minute and the NTL scores, respectively. Female gender, younger age, higher education, and higher income were related to higher scores. CONCLUSION: Patients with HF may be inaccurately categorized as having low or marginal health literacy when the S TOFHLA time limits are enforced. New ways to assess health literacy in older adults are needed. PMID- 22041325 TI - Uncovering interim clinical events at the time of clinical encounter by reviewing intrathoracic impedance threshold crossings. AB - BACKGROUND: Acute decreases in intrathoracic impedance monitored by implanted devices have been shown to precede heart failure exacerbations, although there is still debate regarding its clinical utility in predicting and preventing future events. However, the usefulness of such information to direct patient encounter and enhance patient recall of relevant preceding clinical events at the point of care has not been carefully examined. METHODS AND RESULTS: In this multicenter study, we interviewed 326 patients with heart failure who received an implanted device with intrathoracic impedance-monitoring capabilities both before and after device information was reviewed. We compared the self-reported clinically relevant events (including heart failure hospitalizations, signs and symptoms of worsening heart failure, changes in diuretic therapy, or other fluid-related events) obtained before and after device interrogation, and then examined the relationship between such events with impedance trends documented by the devices. Over 333 +/- 96 days of device monitoring, 215 of 326 patients experienced 590 intrathoracic impedance fluid index threshold-crossing events at the nominal threshold value (60 Omega-d). Review of device-derived information led to the discovery of 221 (37%) previously unreported clinically relevant events in 138 subjects. This included 60 subjects not previously identified as having had clinically relevant events (or 35% of the 171 subjects who did not report events). CONCLUSIONS: Our data demonstrated that reviewing device-derived intrathoracic impedance trends at the time of clinical encounter may help uncover self-reporting of potential clinically relevant events. PMID- 22041326 TI - Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure. AB - BACKGROUND: Iron is an indispensable element of hemoglobin, myoglobin, and cytochromes, and, beyond erythropoiesis, is involved in oxidative metabolism and cellular energetics. Hence, iron deficiency (ID) is anticipated to limit exercise capacity. We investigated whether ID predicted exercise intolerance in patients with systolic chronic heart failure (CHF). METHODS AND RESULTS: We prospectively studied 443 patients with stable systolic CHF (age 54 +/- 10 years, males 90%, ejection fraction 26 +/- 7%, New York Heart Association Class I/II/III/IV 49/188/180/26). ID was defined as: serum ferritin <100 MUg/L or serum ferritin 100-300 MUg/L with serum transferrin saturation <20%. Exercise capacity was expressed as peak oxygen consumption (VO(2)) and ventilatory response to exercise (VE-VCO(2) slope). ID was present in 35 +/- 4% (+/-95% confidence interval) of patients with systolic CHF. Those with ID had reduced peak VO(2) and increased VE VCO(2) slope as compared to subjects without ID (peak VO(2): 13.3 +/- 4.0 versus 15.3 +/- 4.5 mL*min*kg, VE-VCO(2) slope: 50.9 +/- 15.8 versus 43.1 +/- 11.1, respectively, both P < .001, P < .05). In multivariable models, the presence of ID was associated with reduced peak VO(2) (beta = -0.14, P < .01 P < .05) and higher VE-VCO(2) slope (beta = 0.14, P < .01 P < .05), adjusted for demographics and clinical variables. Analogous associations were found between serum ferritin, and both peak VO(2) and VE-VCO(2) slope (P < .05). CONCLUSIONS: ID independently predicts exercise intolerance in patients with systolic CHF, but the strength of these associations is relatively weak. Whether iron supplementation would improve exercise capacity in iron-deficient subjects requires further studies. PMID- 22041327 TI - Low systolic blood pressure at admission predicts long-term mortality in heart failure with preserved ejection fraction. AB - BACKGROUND: Systolic blood pressure (SBP) at hospital admission predicts in hospital and postdischarge mortality in patients with left ventricular systolic dysfunction. The relationship between admission SBP and mortality in heart failure with preserved (>=50%) ejection fraction (HFPEF) is still unclear. METHODS AND RESULTS: We aimed to investigate the relationship between admission SBP and 5-year outcome in 368 consecutive patients hospitalized for new-onset HFPEF. Five-year all-cause mortality rates according to admission SBP categories (<120, 120-139, 140-159, 160-179, and >=180 mm Hg) were 75 +/- 7%, 53 +/- 6%, 52 +/- 7%, 55 +/- 4%, and 60 +/- 7%, respectively (P = .029). Survival analysis showed an inverse relation between admission SBP and mortality with increased risk of death for SBP <120 mm Hg. SBP <120 mm Hg independently predicted 5-year all-cause mortality (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.08-2.63) and cardiovascular mortality (adjusted HR 1.89, 95% CI 1.21 2.97). In patients discharged alive, after adjustment for medical treatment at discharge, admission SBP <120 mm Hg remained predictive of all-cause mortality (adjusted HR 1.52, 95% CI 1.04-2.43) and cardiovascular mortality (adjusted HR 1.69, 95% CI 1.06-2.73). There was no interaction between any of the therapeutic classes and outcome prediction of SBP. CONCLUSIONS: In HFPEF, low SBP (<120 mm Hg) at the time of hospital admission is associated with excess long-term mortality. Further studies are required to determine the mechanism of this association. PMID- 22041328 TI - Hemodynamic effects of exercise training in heart failure. AB - BACKGROUND: Exercise performance improvement after training in heart failure (HF) can be due to central or peripheral changes. METHODS AND RESULTS: In 70 HF stable patients we measured peak VO(2) and cardiac output (CO, inert gas rebreathing technique) and calculated arteriovenous O(2) differences (a-v O(2)diff) before and after an 8-week training program. Peak VO(2) changed from 1111 +/- 403 mL/minute to 1191 +/- 441 (P < .001), peak workload from 68 +/- 29 watts to 76 +/ 32 (P < .0001), peakCO from 6.6 +/- 2.2 L/minute to 7.3 +/- 2.5 (P < .0001), and peak a-v O(2)diff from 17.5 +/- 5.1 mL/100 mL to 16.6 +/- 4.1 (P = .081). Changes in peak CO and a-v O(2)diff allowed to identify 4 behaviors: group 1: (n = 15) reduction in peak CO and increase in a-v O(2)diff (peak VO(2) unchanged, peak workload +9.5%); group 2: (n = 16) both peak CO and a-v O(2)diff increased as well as peak VO(2) (23%) and workload (18%); group 3: (n = 4) peak CO and a-v O(2)diff reduced as well as peak VO(2) (-18%) and workload (-5%); group 4: (n = 35) peak CO increased with a-v O(2)diff reduced (increase in peak VO(2) by 5.5 and workload by 8.4%). CONCLUSIONS: Exercise training improves peakVO(2) by increasing CO with unchanged a-v O(2)diff. A reduction after training of a-v O(2)diff with an increase in CO is frequent (50% of cases), is suggestive of blood flow redistribution and, per se, not a sign of reduced muscle performance been associated with improved exercise capacity. PMID- 22041329 TI - A cellular microRNA, let-7i, is a novel biomarker for clinical outcome in patients with dilated cardiomyopathy. AB - BACKGROUND: Our previous studies have reported that activation of Toll-like receptor (TLR) 4 is implicated in the etiology of human dilated cardiomyopathy (DCM). A recent report has demonstrated that let-7i, a member of the let-7 family of cellular microRNAs (miRs) miR-21, miR-126, and miR-155, directly regulate TLR4 expression. The aim of this study was to determine whether let-7i, miR-21, miR 126, and miR-155 are expressed with TLR4 in human DCM, and whether let-7i levels are related to clinical outcomes. METHODS AND RESULTS: Endomyocardial biopsy tissues were obtained from 103 patients with DCM and 37 subjects without left ventricular (LV) dysfunction as control subjects. Levels of let-7i, miR-126, and miR-155 were lower in the DCM group than in the controls, whereas levels of miR 21 and TLR4 (both mRNA and protein) were higher in the DCM group than in the control group. Levels of let-7i were negatively correlated with TLR4 protein levels in all subjects. After a mean follow-up period of 509 days, 6 DCM patients (5.8%) had died due to a cardiac cause and 15 (14.6%) had developed heart failure. When patients with DCM were divided into tertiles according to let-7i levels, log-rank analysis showed that the DCM subgroup with low let-7i levels was associated with poor clinical outcomes (P = .02). CONCLUSIONS: A decrease in let 7i may be related to poor clinical outcomes in patients with DCM. PMID- 22041330 TI - Left ventricular geometry, global function, and dyssynchrony in infants and children with pompe cardiomyopathy undergoing enzyme replacement therapy. AB - BACKGROUND: Enzyme replacement therapy (ERT) for infantile-onset Pompe disease effectively reduces the left ventricular (LV) mass. This study sought to explore detailed process of LV reverse remodeling after ERT with the use of tissue Doppler and stain rate imaging. METHODS AND RESULTS: Nine infants and children with Pompe cardiomyopathy undergoing ERT for >=1 year, as well as 36 healthy control subjects, were studied. Global systolic and diastolic function was evaluated by peak systolic and early-diastolic velocity at mitral annulus. Temporal systolic and diastolic dyssynchrony was evaluated by the coefficient of variation of the time from the QRS complex to peak systolic and early-diastolic strain rate among 12 LV segments. All pre-ERT patients had impaired global systolic and diastolic function as well as increased regional dyssynchrony (P < .001 for each of all). During the regression of LV hypertrophy, all of these functional indices improved (P for trend <.001), with temporal diastolic dyssynchrony being a significant factor linking to LV mass index in multivariate analysis (P < .001). CONCLUSIONS: ERT improved global LV function and dyssynchrony in Pompe patients. The relationship between LV mass and temporal diastolic dyssynchrony during reverse remodeling suggested a pathophysiologic role of dyssynchrony in Pompe cardiomyopathy. PMID- 22041331 TI - Body temperature circadian rhythm variability corresponds to left ventricular systolic dysfunction in decompensated cardiomyopathic hamsters. AB - BACKGROUND: A declining amplitude of body temperature circadian rhythm (BTCR) predicts decompensation or death in cardiomyopathic hamsters. We tested the hypothesis that changes in BTCR amplitude accompany significant changes in left ventricular (LV) size and function. METHODS AND RESULTS: Using intraperitoneal transmitters, we continuously monitored the temperature of 30 male BIO TO-2 Syrian dilated cardiomyopathic hamsters. Cosinor analysis was used to detect significant changes--defined as changes >1 standard deviation from the baseline amplitude for 3 consecutive days--in BTCR amplitude over each hamster's lifespan. The Student t-test was used to compare BTCR variability and LV size and function (as assessed by 2D echocardiography) between baseline and the time that BTCR amplitude declined. All hamsters received 10 mg/kg furosemide daily. At the time of BTCR amplitude decline, functional parameters had changed significantly (P < .0001) from baseline: ejection fraction (0.31 +/- 0.09% vs. 0.52 +/- 0.08%), LV end-systolic volume (0.11 +/- 0.03 vs. 0.05 +/- 0.02 cm(3)), and LV end-diastolic volume (0.16 +/- 0.04 vs. 0.10 +/- 0.03 cm(3)). CONCLUSIONS: In decompensated cardiomyopathic hamsters, a decline in BTCR amplitude was associated with progression of heart failure and cardiac decompensation. Variation in BTCR warrants further investigation because of its potential implications for the diagnosis and treatment of cardiovascular disorders. PMID- 22041332 TI - Flexible diuretic titration in chronic heart failure: where is the evidence? AB - BACKGROUND: Several sets of heart failure (HF) consensus/guideline statements support the use of a flexible diuretic dosing regimen for HF outpatient management of fluid overload-related signs and symptoms. However, despite the widespread acceptance of such an approach, the evidence supporting the effectiveness of this approach in improving clinical outcomes is unknown. The primary objective of this manuscript was to summarize and review the evidence supporting the use of a flexible diuretic regimen in the management of outpatient heart failure patients. METHODS AND RESULTS: A systematic review was performed, and 9 studies were identified relevant to the question of flexible diuretic titration in the setting of chronic heart failure. Among the 9 studies, 5 were randomized. Three of the randomized trials included flexible diuretic titration as part of a broader multifaceted disease management program, and only 2 were designed to specifically evaluate the sole contribution of flexible diuretic titration. Collectively, data from all of the studies reviewed supported the idea that flexible and individualized diuretic dosing is potentially associated with reduced emergency room visits, reduced rehospitalization, and improved quality of life in HF patients with reduced ejection fraction. CONCLUSIONS: To date, only 2 randomized clinical studies were identified that were designed to determine the effects of a flexible diuretic dosing regimen in outpatient HF patients with reduced ejection fraction. Data are lacking in HF patients with preserved ejection fraction. There is a critical need to test this strategy in well designed prospective randomized clinical trials. PMID- 22041333 TI - The evidence base for diuretic therapy. PMID- 22041334 TI - Left ventricular function in adult patients with atrial septal defect: implication for development of heart failure after transcatheter closure. AB - Despite advances in device closure for atrial septal defect (ASD), post-closure heart failure observed in adult patients remains a clinical problem. Although right heart volume overload is the fundamental pathophysiology in ASD, the post closure heart failure characterized by acute pulmonary congestion is likely because of age-related left ventricular diastolic dysfunction, which is manifested by acute volume loading with ASD closure. Aging also appears to play important roles in the pathophysiology of heart failure through several mechanisms other than diastolic dysfunction, including ventricular systolic and vascular stiffening and increased incidence of comorbidities that significantly affect cardiovascular function. Recent studies suggested that accurate assessment of preclosure diastolic function, such as test ASD occlusion, may help identify high-risk patients for post-closure heart failure. Anti-heart failure therapy before device closure or the use of fenestrated device appears to be effective in preventing post-closure heart failure in the high-risk patients. However, the long-term outcome of such patients remains to be elucidated. Future studies are warranted to construct an algorithm to identify and treat patients at high risk for heart failure after device closure of ASD. PMID- 22041335 TI - Catheter ablation for atrial fibrillation in patients with left ventricular systolic dysfunction. A systematic review and meta-analysis. AB - BACKGROUND: Atrial fibrillation (AF) and heart failure are often coexisting major public health burdens. Although several studies have reported partial restoration of systolic left ventricular (LV) function after catheter ablation for AF, the method is not widely applied in patients with LV dysfunction. We reviewed the results of AF ablation in patients with systolic LV dysfunction. METHODS AND RESULTS: PubMed was searched for studies published after 2000 reporting original data on AF catheter ablation in adult patients with systolic LV dysfunction. Primary end point was the change of LV ejection fraction (LVEF) after catheter ablation; secondary endpoints were the changes of exercise capacity and quality of life after the procedure. We calculated mean difference (MD) of LVEF and 95% confidence interval (95% CI) using random-effects models. Heterogeneity was investigated by I(2) statistic, publication bias with Egger's test. The impact of covariates on LVEF improvement was evaluated with meta-regression analyses. Nine studies with a total of 354 patients with systolic LV dysfunction were analyzed. Study patients were mainly male with mean age 49 to 62 years, LVEF was moderately impaired and ranged in all but 1 study from 35% to 43%. LVEF improved after ablation with a MD of 11.1% (95% CI: 7.1-15.2, P < .001). Heterogeneity among analyzed studies was significant (I(2) = 92.9, P < .001). No potential publication bias was found. In meta-regression analyses, the proportion of patients with coronary artery disease was inversely related with LVEF improvement (P < .0001) whereas there was no association between the LVEF change and the proportion of patients with nonparoxysmal AF or the proportion of patients without AF recurrences during follow-up. CONCLUSIONS: AF ablation in patients with systolic LV dysfunction results in significant improvement of LV function, but the extent of this improvement is heterogeneous. Patients with coronary artery disease seem to benefit less than patients with other underlying diseases. These results may be explained by patient selection. PMID- 22041337 TI - Functional results of burned hands treated with Integra(r). AB - INTRODUCTION: Dermal substitutes, such as Integra((r)) introduced as a new alternative to our surgical arsenal and its use in burn treatment, in both acute and chronic phases, have gained great importance. OBJECTIVE: The aim of the experiment is to describe the results of the functional evaluation of patients with burned hands treated with Integra((r)) in both acute and chronic phases. MATERIAL AND METHODS: A retrospective review of a transversal cohort. Patient characteristics evaluated were sociodemographic characteristics, burn mechanism, burn extension and depth, treatments received previous to Integra((r)) and complications related to its use. Clinical and photographic evaluations were performed evaluating skin elasticity, range of articular movement, prehensile strength, pain and functional evaluation using the validated 400 Point Evaluation Test. RESULTS: A total of 17 burned hands in 14 right-handed patients, were treated with Integra((r)), three being bilateral hand burns. Eleven were treated in the acute phase and in nine in the scar reconstruction phase. Range of articular motion was complete in 15 of 17 hands. In 88% of the hands, flexible skin coverage was achieved. No statistically significant difference was observed in prehension strength of the burned hand versus the contralateral non-burned hand. Sixteen hands had a painless evolution. The 400 Point Evaluation score was 92.8 +/- 6.3% (80 - 100%). Nearly four-fifths (79%) of the patients returned to normal active working activities. PMID- 22041338 TI - Creating a working group for prenatal diagnosis and management as a venue to facilitate neurosurgery health care delivery. AB - BACKGROUND/AIMS: To facilitate the communication and engagement with the parents of a fetus with a neurosurgical condition, as well as subsequent care of the newborn, the Division of Pediatric Neurosurgery of the University of Florida College of Medicine Jacksonville created a multidisciplinary working group. METHODS: The University of Florida Division of Pediatric Neurosurgery performed a staged process to develop a multidisciplinary prenatal working group. Phase I: establish communications with perinatology, neonatology and radiology. Phase II: initiate clinical working sessions with neurosurgery, neonatology, perinatology, radiology. Phase III: the working sessions were progressively expanded to include other specialties of interest. RESULTS: This report addresses the development and the subsequent monthly meetings that were held between March 2004 and October 2008. There were a total of 246 pregnancies in which a significant fetal condition was present. Of these, 53 generated neurosurgical consultations on the basis of fetal imaging (ultrasound and/or MRI). Those that required postnatal surgery were able to have timely coordinated scheduled delivery and subsequent neurosurgical procedures. CONCLUSIONS: If neurosurgeons do not have access to a multidisciplinary prenatal working group, they may take the lead and facilitate the establishment of such a team approach. This can lead to better prenatal communications with the parents/families, coordination of delivery and timely postnatal neurosurgical management. PMID- 22041339 TI - Neuropathological investigation of the hypometabolic regions on positron emission tomography with [18F] fluorodeoxyglucose in patients with dementia with Lewy bodies. AB - We performed a quantitative neuropathological examination of the hypometabolic regions on FDG PET in dementia with Lewy bodies (DLB), Alzheimer's disease (AD) and control cases. When the DLB cases were divided into two groups according to concomitant AD pathology (ADP), neuronal loss in the temporo-parietal association area was milder in the DLB groups than in the AD group, although there were no differences between the two DLB groups. Tau and Abeta immunoreactivities were observed in the AD group and the DLB group with ADP, but were rare in the DLB group without ADP. Tau and Abeta immunoreactivities as well as numbers of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) were more common in the AD group than in the DLB group with ADP. There was no difference in neuronal loss in the occipital area among the three groups. alpha-Synuclein immunoreactivity was observed in the DLB groups but not in the AD group. There were no differences in alpha-synuclein immunoreactivity and number of Lewy bodies (LBs) between the two DLB groups. These findings indicate that the neuropathological bases of the hypometabolic regions in the temporo-parietal association and occipital area in DLB may be AD pathology and Lewy pathology, respectively. PMID- 22041340 TI - Cigarette smoking and its association with overlapping gastroesophageal reflux disease, functional dyspepsia, or irritable bowel syndrome. AB - BACKGROUND: Gastroesophageal reflux disease (GERD), functional dyspepsia (FD), and irritable bowel syndrome (IBS) are common gastrointestinal diseases. Several studies have shown a significant occurrence of overlap among these 3 diseases. The purpose of this study was to examine the factors associated with such disease overlap in Japanese adults. METHODS: We performed a cross-sectional study on Japanese workers who visited a clinic for a routine health check-up and asked them to fill out a self-report questionnaire. GERD was defined as episodes of heartburn and/or acid regurgitation at least once a week, and the diagnosis of FD and IBS was based on Rome III criteria. A logistic regression model was used to identify risk factors, and odds ratio (OR) was calculated with 95% confidence intervals (CIs). RESULTS: Disease overlaps were found in 160 (6.0%) of the 2680 eligible subjects. Female gender was associated with GERD + IBS (OR=1.99; 95% CI, 1.06-3.75), and FD + IBS (OR=1.72; 95% CI, 1.03-2.85), and lower body mass index was negatively associated with FD + IBS (OR=0.54; 96% CI, 0.34-0.87). Cigarette smoking was a common factor associated with the overlaps: GERD + FD (OR=2.14; 95% CI, 1.22-3.76), GERD + IBS (OR=3.16; 95% CI, 1.75-3.71), FD + IBS (OR=2.26; 95% CI, 1.40-3.66), and GERD + FD + IBS (OR=4.08; 95% CI, 1.66-10.07). The associations between smoking habits and overlaps were stronger in smokers who smoked >=1 pack per day as compared to those who smoked <1 pack per day. CONCLUSION: Cigarette smoking was significantly associated with overlaps among GERD, FD, and IBS in Japanese adults. PMID- 22041341 TI - Time-course of changes of visceral fat area, liver volume and liver fat area during intragastric balloon therapy in Japanese super-obese patients. AB - OBJECTIVE: The aim of this study was to assess the changes in the clinical parameters during intragastric balloon therapy for Japanese obese patients. METHODS: Between March 2009 and September 2010, 8 patients underwent intragastric balloon therapy at our hospital. The visceral fat area, liver volume and the liver-spleen ratio were measured by computed tomography. Blood examination and computerized tomography were performed before the balloon placement, and at 1, 3 and 6 months after the balloon placement in all of the patients. RESULTS: Eight patients (5 males and 3 females, median age, 39 years; median BMI, 44.0 kg/m(2)) underwent intragastric balloon therapy without severe complications. The median weight loss was 8.6 kg, mean BMI loss was 2.8 kg/m(2), and the percent excess weight loss was 14.8% at 6 months after the balloon placement. The body weight and liver volume decreased significantly during the first month, and the results were maintained at the same levels until after the second month. The liver-spleen ratio also improved significantly during the first month, but worsened again during the last 3 months. The visceral fat area showed no significant differences during the treatment as well as no differences in liver enzymes, glucose and lipid metabolism. CONCLUSION: Intragastric balloon therapy achieved a moderate effect in weight and liver volume reduction during the early months of the treatment. Intragastric balloon therapy may have a role as a minimally invasive method for pretreatment before laparoscopic surgery. PMID- 22041342 TI - CCR2 polymorphism in chronic renal failure patients requiring long-term hemodialysis. AB - OBJECTIVE: A number of chemokines and chemokine receptors are produced by intrinsic renal cells as well as by infiltrating cells during renal inflammation. The CCR2 chemokine receptor mediates leukocyte chemoattraction in the initiation and amplification phase of renal inflammation. The polymorphism, CCR2-V64I, changes valine 64 of CCR2 to isoleucine. We aimed to determine the frequency of CCR2-V64I polymorphism in patients with chronic renal failure requiring long-term hemodialysis. METHODS AND PATIENTS: The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the gene frequencies of CCR2 641 in CRF patients (n=210) and healthy controls (n=139) in the current study. RESULTS: The frequencies of the CCR2 genotype were 0.68 for V/V, 0.28 for V/I, and 0.4 for I/I in the CRF patients and 0.81 for V/V, 018 for V/I and 0.1 for I/I in healthy controls. The distribution of the CCR2-V64I mutant genotype was significantly different between subjects with CRF and healthy control subjects (X2=7.197 and p=0.027). CONCLUSION: We found that the CCR2-V64I polymorphism was significantly high in CRF patients. In addition to the contribution to disease pathogenesis, it was recently found that chemokines have therapeutic importance in chronic renal failure. The frequency of CCR2-V64I and other chemokine and chemokine receptor polymorphisms in renal pathologies must be further investigated in larger study populations and in different renal diseases. PMID- 22041343 TI - Retrospective comparison of the clinical and angiographic outcomes of the sirolimus-eluting stent and the bare-metal stent in 2031 nonrandomized consecutive de novo native coronary lesions. AB - OBJECTIVE: To evaluate the mid-term outcomes of sirolimus-eluting stents (SES; Cypher Bx Velocity) for de novo coronary stenosis in a Japanese clinical setting, and to compare these with the outcomes using bare-metal stents (BMS). METHODS: This study was a nonrandomized, lesion-based, and single-center study, retrospectively investigated in October 2010. We enrolled 2031 consecutive cases with de novo coronary lesions treated with BMS (n=587) or SES (n=1,444) from January 2003 to May 2007. SES use ratio during the available interval was 95.5%. The primary endpoint was the incidence of target vessel failure (TVF: comprising cardiac death, nonfatal recurrent MI, definite stent thrombosis (ST), and severe restenosis [% diameter stenosis (%DS) at secondary angiography >=70%]. The secondary endpoint was the incidence of binary in-stent restenosis (%DS >50%). RESULTS: The TVF ratio after SES placement (6.6%) was significantly lower than that after BMS placement (11.8%, p<0.001), despite many disadvantageous variables in the SES group. SES related to the risk of TVF (mean follow-up for SES, 1,411 +/- 539 days; BMS, 1,818 +/- 825 days) (hazard ratio of 0.428 at 95% CI, 0.292 0.627, p<0.001). The ratio of binary in-stent restenosis after SES placement (13.4%) was significantly lower than that after BMS placement (25.1%; p<0.001). SES was significantly related to binary in-stent restenosis (odds ratio of 0.267 at 95% CI, 0.195-0.366, p<0.001). CONCLUSION: SES has a more favorable mid-term clinical and angiographic outcome than BMS for de novo coronary stenosis in clinical settings in Japan. PMID- 22041344 TI - Admission glucose level and in-hospital outcomes in diabetic and non-diabetic patients with ST-elevation acute myocardial infarction. AB - BACKGROUND: Hyperglycemia on admission is a predictor of an unfavorable prognosis in patients with ST-elevation Acute Myocardial Infarction (AMI). Data concerning associations between an elevated glucose level on admission and other in-hospital complications are still limited. METHODS: A total of 1,137 AMI patients with complete admission blood glucose level (ABGL) analysis were identified and stratified according to ABGL. RESULTS: A total of 16.1% patients had admission glucose level <5 mmol/L, 36.1% <7 mmol/L, 20.2% <9 mmol/L, 9.9% <11 mmol/L and 17.7% >=11 mmol/L. Compared with the euglycemia group, both the hypo- and hyperglycemia groups were associated with higher in-hospital mortality. In hospital mortality of diabetic patients with hypoglycemia (12.2%) was higher than that of diabetic patients with either euglycemia or mild hyperglycemia (11.1%, or 10.7% relatively). The same results were seen in non-diabetic patients. In the logistic regression analysis, admission glucose and cardiac function of Killip grade were the independent predictors of in-hospital death for patients with AMI. CONCLUSION: Elevated admission glucose levels are associated with an increased risk of life-threatening complications in diabetic and non-diabetic AMI patients. Compared with the euglycemia group, hypoglycemia was associated with a higher trend of in-hospital mortality. PMID- 22041345 TI - Comparison of the efficacy and safety of single-pill fixed-dose combinations of losartan/hydrochlorothiazide and valsartan/hydrochlorothiazide in patients with hypertension (SALT-VAT study). AB - OBJECTIVE: We analyzed the efficacy and safety of Preminent((r)) [losartan (50 mg/day)/HCTZ (12.5 mg/day)] compared to CodioMD((r)) [valsartan (80 mg/day)/HCTZ (6.25 mg/day)]. METHODS: In this study, 31 hypertensive patients after receiving 3 months of Preminent((r)) (Stage A) were enrolled. We applied a changeover with switching from Preminent((r)) to CodioMD((r)) (Stage B). We then applied another changeover with switching from CodioMD((r)) to Preminent((r)) after 3 months (Stage C). RESULTS: Average values of 24-h blood pressure (BP), daytime BP and nighttime BP using ambulatory BP monitoring (ABPM) significantly increased from Stage A to B [4/3 mmHg, 5/3 mmHg and 3/3 mmHg, respectively]. Average values of 24-h BP, morning BP, daytime BP, nighttime BP significantly decreased from the end of Stage B to C [-5/-5 mmHg, -4/-6 mmHg, -5/-5 mmHg and -6/-4 mmHg, respectively]. Interestingly, the serum levels of uric acid and the urinary albumin/creatinine ratio showed a significant increase after the change to CodioMD((r)). Since these adverse effects did not disappear after the return to Preminent((r)) at the end of Stage C, we performed an additional 3-month follow up (extended stage). These adverse effects finally disappeared at the end of this extended stage. CONCLUSION: Single-pill fixed-dose combination therapy using Preminent((r)) showed significant 24-h BP-lowering effects and was safe when compared with CodioMD((r)). PMID- 22041346 TI - Elevated depressive symptoms are associated with hypertriglyceridemia in Japanese male workers. AB - OBJECTIVE: The aim of this study was to determine whether elevated depressive symptoms are associated with metabolic syndrome and its components in the Japanese population. METHODS: Out of 1,386 male workers who underwent measurements of variables of metabolic syndrome components in their health checkup, 1,186 subjects (44.5 +/- 9.6 years) completed the Zung self-rating depression scale (ZSDS) (response rate 85.6%). In this study, metabolic syndrome was defined according to the joint scientific statement proposed by 6 major organizations, including the International Diabetes Federation. RESULTS: The overall frequency of elevated depressive symptoms (ZSDS scores >=40) was 42.1% (n=499). The incidence of metabolic syndrome was significantly higher in subjects with elevated depressive symptoms than in those without (13.2% vs. 8.9%, p<0.05). Of all the metabolic syndrome components, mean triglyceride levels were significantly higher in subjects with elevated depressive symptoms than in those without [124.7 (95% confidence interval (CI): 117.8-131.7) mg/dL vs. 111.5 (95% CI: 107.2-115.9) mg/dL, p<0.05]. Consequently, hypertriglyceridemia (28.9% vs. 21.0%, p<0.01) was the main component correlated with the between-group difference of metabolic syndrome incidence. In the logistic regression analysis after adjustment for potential confounders, the odds ratio of the total ZSDS scores for the diagnosis of hypertriglyceridemia was 1.52 (95% CI: 1.13-2.04; p<0.01), and the major depressive symptom was psychomotor agitation (odds ratio: 1.47; 95% CI: 1.10-1.94; p<0.01). CONCLUSION: This study showed that elevated depressive symptoms were associated with hypertriglyceridemia in Japanese male workers, which affected the clinical diagnosis of metabolic syndrome. PMID- 22041347 TI - Longitudinal study on white blood cell count and the incidence of metabolic syndrome. AB - OBJECTIVE: Many studies have revealed that white blood cell count (WBC) is related to insulin resistance which is a central mechanism of metabolic syndrome (MetS). However, few cohort studies have examined the role of WBC in the development of MetS. We hypothesized that WBC is associated with the future development of MetS, and investigated the longitudinal incidence of MetS in healthy workers. METHODS: WBC was measured in 5,073 workers (mean age 42.5 years) without MetS at baseline. The incidence of MetS was monitored over 7 years of follow-up, in relation to quartiles of WBC. During the follow-up, 925 participants were diagnosed as MetS. RESULTS: Incidence of MetS was increased in participants with higher WBC: the rates of incidence of MetS were 22.6, 32.9, 42.9, and 57.5 per 1,000 person-years of follow-up in the 1st, 2nd, 3rd, and 4th quartiles of WBC, respectively. After adjustments for confounding factors, the adjusted hazards ratio (95% confidence interval) for MetS was 1.00 (reference), 1.22 (0.98 to 1.51), 1.52 (1.24 to 1.87), and 1.66 (1.35 to 2.04) through the quartiles of WBC, respectively, (p <0.001). This relationship was consistent among current smokers and never smokers, and among male and female genders, respectively. CONCLUSION: WBC is useful in predicting the future development of MetS which leads to atherosclerotic diseases. PMID- 22041348 TI - Association of short sleep duration with obesity, diabetes, fatty liver and behavioral factors in Japanese men. AB - OBJECTIVE: Sleep is one of the major means to maintain health. The association of short sleep duration with obesity, diabetes, fatty liver and behavioral factors requires further exploration. METHODS: A total of 8157 Japanese men who underwent health evaluations were divided into 3 groups by sleep duration <5 hours, 5~<7 hours and >=7 hours. Poor sleep was self-reported, being defined as difficulty of getting to sleep or awakening easily. The age-adjusted and age and poor sleep adjusted odds ratios of the 3 groups for obesity, diabetes, fatty liver, mental stress, poor sleep, regular exercise and late dinner time were investigated. RESULTS: Compared to the sleep duration 5~<7 hours group, the age-adjusted odds ratios of the <5 hours group were significantly higher for obesity (1.42), diabetes (1.63), mental stress (1.75), poor sleep (1.85), late dinner time (1.47), and significantly lower for regular exercise (0.61); while those of the >=7 hours group were significantly lower for obesity (0.73), fatty liver (0.82), mental stress (0.73), poor sleep (0.69), late dinner time (0.45), and significantly higher for regular exercise (1.27). Above significances still existed after adjustment for age and poor sleep. CONCLUSION: Short sleep duration is associated with obesity, diabetes, fatty liver and multiple behavioral factors. The optimal sleep duration for health promotion and effective actions for obtaining optimal sleep, including modifications of behavioral and environmental factors, should be one of the major concerns of public health. PMID- 22041349 TI - Antithrombotic drug therapy for IgA nephropathy: a meta analysis of randomized controlled trials. AB - BACKGROUND: Antithrombotic agents, including antiplatelet agents, anticoagulants and thrombolysis agents, have been widely used in the management of immunoglobulin A (IgA) nephropathy in Chinese and Japanese populations. To systematically evaluate the effects of antithrombotic agents for IgA nephropathy. METHODS: Data sources consisted of MEDLINE, EMBASE, the Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodicals Databases (CNKI) and Japana Centra Revuo Medicina (http://www.jamas.gr.jp) up to April 5, 2011. The quality of the studies was evaluated from the intention to treat analysis and allocation concealment, as well as by the Jadad method. Meta analyses were performed on the outcomes of proteinuria and renal function. RESULTS: Six articles met the predetermined inclusion criteria. Antithrombotic agents showed statistically significant effects on proteinuria (p<0.0001) but not on the protection of renal function (p=0.07). The pooled risk ratio for proteinuria was 0.53, [95% confidence intervals (CI): 0.41-0.68; I(2)=0%] and for renal function it was 0.42 (95% CI 0.17-1.06; I(2)=72%). Subgroup analysis showed that dipyridamole was beneficial for proteinuria (p=0.0003) but had no significant effects on protecting renal function. Urokinase had statistically significant effects both on the reduction of proteinuria (p=0.0005) and protecting renal function (p<0.00001) when compared with the control group. CONCLUSION: Antithrombotic agents had statistically significant effects on the reduction of proteinuria but not on the protection of renal function in patients with IgAN. Urokinase had statistically significant effects both on the reduction of proteinuria and on protecting renal function. Urokinase was shown to be a promising medication and should be investigated further. PMID- 22041350 TI - Clinical features of renal amyloidosis: an analysis of 40 patients in a 28-year follow-up. AB - OBJECTIVE: Although rare, renal amyloidosis is an important diagnosis that bares a significant morbidity and mortality. The purpose of this study was to present current single center experience in the past 28 years. METHODS: A total of 6151 kidney biopsies were performed in our hospital from Jan. 1983 to Dec. 2010; 5844 were native kidney biopsies. Cases with a diagnosis of renal amyloidosis were identified through a search of our data bank and the clinical data were retrieved from medical charts. The patients were further classified as AL type and non-AL type. The trend of incidence was analyzed and the clinical features were compared. Risk factors that predict patient mortality were discovered by logistic regression analysis. RESULTS: Forty out of 5844 native kidney biopsies (0.68%) were identified as renal amyloidosis. Eighteen (45%) were of AL type. The mean age at diagnosis was 62.6 +/- 13.4 years. Male was the predominant gender that was involved. Clinically, most (80%) have nephrotic range proteinuria (mean 24 hours urine protein: 6.9 +/- 4.7 g). With a mean follow-up duration of 1155 day, the 1-year and 5-year patient survival were 42.9% and 17.9%, respectively. eGFR at biopsy was the sole predictive factor for patient survival. CONCLUSION: Senile patients with nephrotic syndrome should elicit the suspicion of renal amyloidosis. The incidence appeared to be increasing and the prognosis poor. PMID- 22041351 TI - Prognosis of patients on continuous ambulatory peritoneal dialysis (CAPD) for over 10 years. AB - BACKGROUND: Patients who have been on continuous ambulatory peritoneal dialysis (CAPD) for over 10 years are known to have a risk of developing encapsulating peritoneal sclerosis (EPS). However, the prognosis of patients on CAPD for over 10 years remains unclear. METHODS: To better understand the efficacy of a variety of treatments for EPS, we retrospectively reviewed 25 patients who started CAPD at Toranomon Hospital from 1981 to 1997 and continued it for longer than 10 years. RESULTS: The CAPD catheter was removed without peritoneal lavage in the initial 3 patients and they developed massive ascites. They all died of infection without resolution of the ascites. Accordingly, in the remaining 13 patients who did not undergo kidney transplantation, peritoneal lavage therapy was performed for 12 months before removing the CAPD catheter. As a result, 4 patients did not develop EPS. However, 9 patients had EPS with ascites, among whom 4 died of EPS related diseases and 5 are alive. Five patients underwent cadaveric donor kidney transplantation. At the time of surgery, the CAPD catheter was removed without peritoneal lavage; 1 patient suffered from massive ascites immediately, although this subsided within 3 months after kidney transplantation, and 4 patients remain free from EPS-related symptoms and are doing well. CONCLUSION: Kidney transplantation may be an option for preventing EPS. This study showed that improvement of the uremic state as well as treatment with immunosuppressants including corticosteroids may contribute to preventing EPS. PMID- 22041352 TI - The role of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of mediastinal and hilar lymph node metastases in patients with extrapulmonary malignancy. AB - OBJECTIVE: The determination of mediastinal lymphadenopathy is important in the management of extrapulmonary malignancy. The purpose of this study was to determine the diagnostic performance of EBUS-TBNA in the diagnosis of mediastinal and hilar lymphadenopathy in patients with proven or suspicious extrapulmonary malignancy. PATIENTS AND METHODS: Retrospective analysis was performed in 57 patients (81 lesions) with proven (n=51) or suspicious (n=6) extrapulmonary malignancies who underwent EBUS-TBNA between May 2009 and January 2011. RESULTS: There were 37 male and 20 female patients, with a median age of 64 years. Thirty five (61.4%) patients were confirmed as malignancy (34 extrapulmonary malignancy and 1 primary lung cancer) and 22 (38.6%) patients were confirmed as benign. EBUS TBNA identified malignancy in 30 patients. One patient who was diagnosed as primary lung cancer was excluded from diagnostic performance analysis. Overall cancer prevalence was 61% in 56 study patients. The diagnostic sensitivity, accuracy, and negative predictive value of EBUS-TBNA per patient were 88%, 93%, and 85%. The diagnostic sensitivity, accuracy, and negative predictive value of PET/CT scan per patient were 81%, 82%, and 71%, respectively. There were no serious complications related to EBUS-TBNA. CONCLUSION: Since mediastinal and hilar lymphadenopathy do not always result from metastases in patients with extrapulmonary malignancy, histopathologic confirmation is mandatory. EBUS-TBNA is a sensitive modality and can be considered as the initial test for the histopathological diagnosis of mediastinal and hilar lymphadenopathy in patients with extrapulmonary malignancy. PMID- 22041353 TI - Improvements in quadriceps force and work efficiency are related to improvements in endurance capacity following pulmonary rehabilitation in COPD patients. AB - BACKGROUND AND OBJECTIVE: The endurance time has been reported to be the most sensitive measure of improved exercise capacity in response to a variety of interventions for COPD. The aim of the present study was to determine whether the improvements in quadriceps force and measures obtained from a symptom-limited maximal test contributed to the improvements in endurance time following pulmonary rehabilitation. METHODS: Fifty-seven consecutive COPD subjects completed a 10-week pulmonary rehabilitation program. The subjects completed a symptom-limited incremental cycle ergometry test and a constant work rate test before and after pulmonary rehabilitation. Peripheral and respiratory muscle strength was also measured. The relationships between the change in endurance time and the changes obtained from the incremental test and muscle strength test were investigated. RESULTS: The endurance time showed the greatest improvement among the exercise capacity indices. The changes in endurance time were significantly correlated to changes in quadriceps force, peak work rate, anaerobic threshold and work efficiency on the incremental load test. In the multiple stepwise regression analysis, changes in quadriceps force and work efficiency measured on the maximal exercise test were selected. CONCLUSION: These findings suggest that the improvements in endurance time after pulmonary rehabilitation may be explained by increased quadriceps force and improvements in peak work rate and work efficiency. PMID- 22041354 TI - Nutritional assessment in patients with pulmonary nontuberculous mycobacteriosis. AB - OBJECTIVE: To determine the nutritional factors that influence disease spread in patients with pulmonary Mycobacterium avium complex (MAC) infection. METHODS: A prospective observational study. PATIENTS: Patients with pulmonary MAC infection were enrolled in this study. Chest computed tomography (CT), abdominal CT, and physical, clinical, and nutritional laboratory data were collected after obtaining informed consent. RESULTS: Seventy-eight patients (16 males and 62 females) were consecutively enrolled. While the mean body mass index (BMI) was low (19.6 +/- 2.7 kg/m(2)), the mean serum albumin concentration was within normal range (4.2 +/- 0.2 g/dL). We evaluated the number of affected lung segments to define the degree of disease spread, and examined the relationships between various parameters and disease spread. Multivariate analysis identified the duration of the disease (+1.6 segment/100 months, p=0.03), BMI (-0.5 segment/BMI, p=0.003), and white blood cell count (+0.7 segment/1,000 WBC, p=0.03) as factors contributing to disease spread. CONCLUSION: BMI is an excellent marker for nutritional assessment and for predicting disease spread in patients with pulmonary MAC infection. PMID- 22041355 TI - Impact of cigarette smoking on maximal expiratory flows in a general population: the Takahata study. AB - BACKGROUND: Maximal expiratory flows (MEFs) depend on the elastic recoil pressure in the alveoli, airway resistance and bronchial collapsibility. MEFs at lower levels of vital capacity [MEFs at x% FVC (MEF(x))] would indicate the patency of peripheral airways. In Japan, a ratio of MEF(50) to MEF(25) (MEF(50)/MEF(25)) greater than 4.0 is used as an index of injury to the small airways in subjects without airflow limitation. However, to date there have been no epidemiological investigations relating to this index. The aim of this study was to evaluate the impact of cigarette smoking on MEFs in a general population, and to assess the validity of using this index to evaluate injury to the small airways. METHODS: Subjects aged 40 years or older (n=2,917), who had participated in a community based annual health-check in Takahata, Japan, were enrolled in the study. MEF(75), MEF(50) and MEF(25) were measured in these subjects. RESULTS: In smokers, as compared with never-smokers, the percentage predicted MEFs (%MEFs) decreased according to the aging of the population, except in the case of %MEF(25) in females. In males, but not in females, %MEFs decreased significantly with an increase in cigarette consumption. In both genders, MEF(50)/MEF(25) was slightly, but significantly, elevated with aging of the population. In addition, 36.5% of subjects who participated in this health-check had MEF(50)/MEF(25) values greater than 4.0. No difference in MEF(50)/MEF(25) was observed between smokers and never-smokers. CONCLUSION: Cigarette smoking enhanced the age-related decline in MEFs. Since many healthy subjects aged 40 years or older have MEF(50)/MEF(25) values greater than 4.0, the use of this criterion may over estimate the presence of small airway disease. PMID- 22041356 TI - Differences in the JAK2 and MPL mutation status in the cell lineages of the bcr/abl-negative chronic myeloproliferative neoplasm subtypes. AB - OBJECTIVE: While the somatic mutation of Janus Kinase 2 (JAK2) and the thrombopoietin receptor (c-MPL) gene are thought to affect the pathogenesis of bcr/abl negative chronic myeloproliferative neoplasm (MPN), the relationship between the mutation and the clinical features remain obscure. METHODS: The mutation status of these genes in granulocytes, platelets, T-cells, and erythroid colonies (BFU-E) was obtained from 115 MPN patients, and then the clinical features of the MPN subtypes were compared. RESULTS: The JAK2-V617F mutation was observed in three lineages of granulocytes, platelets, and BFU-E in almost all polycythemia vera (PV) and primary myelofibrosis (PMF) patients. In contrast, 68% of essential thrombocythemia (ET) patients have the JAK2-V617F mutation in at least one of the lineages, of which 70% of these patients have the JAK2-V617F mutation in three lineages; the remaining ET patients with the JAK2-V617F mutation only exhibited the mutation in one or two lineages. Further, the ET patients that exhibited the JAK2-V617F mutation in three lineages had higher WBC and granulocyte counts as compared to the ET patients that did not have the JAK2 V617F mutation or only had the mutation in one or two lineages. Concerning the MPL gene, two ET patients had the MPL-W515L gene mutation in their platelets, although the lineage of the JAK2-V617F mutation involved differed from case to case. CONCLUSION: The progenitor cells that are involved with the JAK2-V617F mutation in MPNs are different in each subtype and this difference may also affect the clinical features of MPNs. PMID- 22041357 TI - Is liver cirrhosis a risk factor for osteonecrosis of the femoral head in adults? A population-based 3-year follow-up study. AB - BACKGROUND: The relationship between osteonecrosis of the femoral head (OFH) and liver cirrhosis is controversial. The aim of this study was to determine whether liver cirrhosis is associated with the occurrence of OFH. METHODS: We used the National Health Insurance Database, derived from the Taiwan National Health Insurance program. The study cohort comprised 40,769 adult patients with liver cirrhosis. The comparison cohort consisted of 40,769 randomly selected age- and sex-matched subjects. RESULTS: During the 3-year follow-up period, there were 321 (0.8%) cirrhotic patients with OFH, and 126 (0.3%) non-cirrhotic patients with OFH (p<0.001). Cox's regression analysis, adjusted by the patients' age, sex, and other confounding factors, showed that the cirrhotic patients had a higher risk for occurrence of OFH than non-cirrhotic patients during the 3-year period (hazard ratio=2.38, p<0.001). In this 3-year study, the incidence density of cirrhotic patients hospitalized for OFH was 3 episodes/1,000 person-year. CONCLUSION: We conclude that cirrhotic patients have a higher risk for occurrence of OFH than non-cirrhotic patients. PMID- 22041358 TI - A case of rectal cancer arising from long-standing prolapsed mucosa of the rectum. AB - Mucosal prolapse syndrome (MPS) has been recognized as a chronic benign inflammatory disorder, characterized mainly by rectal mucosal prolapse. Disorders representing this condition include solitary rectal ulcer syndrome (SRUS), rectal prolapse, proctitis cystica profunda, and inflammatory cap polyps. The gross appearance of rectal MPS can be occasionally misinterpreted as rectal cancer. In contrast, there have been a few reports of colorectal cancer originating from prolapsed mucosa. Herein, we report a case of MPS associated with two independent rectal cancers extending into the submucosal layer. We speculate that long standing MPS may increase the risk of malignant transformation. PMID- 22041359 TI - Small intestine Crohn's disease presenting as fever mistaken for adult onset Still's disease. AB - Crohn's disease (CD) is not rare in recent years, but it is sometimes difficult to make a definite diagnosis particularly if it is in the small intestine. We report a patient with fever for 8 months whose disease was mistaken to be Adult onset Still's disease. The patient was diagnosed small intestine Crohn's disease at last by pathology. We want to emphasize that doctors should not forget small intestine Crohn's disease when encountering an unidentified feverish patient, they should not diagnose a feverish patient of Adult onset Still's disease at once. It is important to note that corticosteroids can conceal many diseases and they should not be considered lightly even if the patient is diagnosed with Adult onset Still's disease. PMID- 22041360 TI - Mesentery neurilemmoma: CT, MRI and angiographic findings. AB - Mesenteric neurilemmoma is extremely rare. We present a case of a 45-year-old man with mesenteric neurilemmoma, with CT, MRI and angiographic findings. The patient was healthy and had had no symptoms previously. CT and MRI images revealed a 2.2 cm well-defined, soft-tissue mass adjacent to the posterior border of the left lobe of the liver. The tumor mass displayed a heterogenous low signal on T2 weighted image and peripheral enhancement after gadolinium administration. Angiography showed a hypervascular mass beneath the tail of pancreas, which was supplied by small branches of middle splenic artery. Histopathology revealed a mesentery neurilemmoma composed of spindle tumor cells. PMID- 22041361 TI - A rare case of infectious colitis with ulcers in the cecum caused by Mycobacterium gordonae. AB - A 69-year-old female complained of persistent abdominal pain, and annular ulcers and ulcer scars were detected endoscopically in the cecum. Pathological findings included caseous granulomas with some Langhans giant cells, and Ziehl-Neelsen staining was negative. Mycobacterium gordonae (M. gordonae) was identified by the DNA-DNA hybridization method and culture (Ogawa medium) of biopsy samples from ulcerous cecal lesions. After 6 months of antibiotic therapy, ulcerous cecal lesions were healed, and no acid-fast bacteria were detected by culture of biopsy samples from scar tissue. We believe this is the first report of M. gordonae infection in the alimentary tract. PMID- 22041362 TI - Recurrent variant angina pectoris due to Behcet's syndrome. AB - We report a case of recurrent variant angina pectoris which occurred even while receiving antispastic treatment. Coronary angiography revealed no obvious lesion. Behcet's syndrome was diagnosed based on recurrent oral aphthous and genital ulcer as well as skin manifestation. After treatment with immunosuppressant, neither angina nor oral ulcer relapsed. We strongly believe that the variant angina is due to coronary vasospasm induced by Behcet's syndrome in this patient. PMID- 22041363 TI - Incessant monomorphic ventricular tachycardia induced by the proarrhythmic effect of amiodarone. AB - This case report describes incessant monomorphic ventricular tachycardia (VT), not torsade de pointes, induced by intravenous amiodarone in a 48-year-old woman with dilated cardiomyopathy. VT was reproducibly triggered by short coupled premature ventricular complex (PVC) with different morphology from VT. After amiodarone infusion, the coupling interval of initiating PVC was prolonged, and moreover, the morphology of initiating PVC became the same as that of VT. Though amiodarone has become the first line drug to treat ventricular tachyarrhythmias in patients with cardiac dysfunction, it is important to be aware of its proarrhythmic effect, which may lead to an electrical storm of monomorphic VT. PMID- 22041364 TI - An adult patient with isolated left ventricular noncompaction presented with atrial fibrillation and complete atrioventricular block. AB - Isolated left ventricular noncompaction (IVNC) is a rare congenital anomaly. The clinical manifestations include congestive heart failure, systemic thromboemboli, arrhythmias and sudden death. We report a case of IVNC in a male patient who presented with atrial fibrillation with complete heart block. PMID- 22041365 TI - Variant angina associated with coronary artery endothelial dysfunction and myocardial bridge: a case report and review of the literature. AB - The association of variant angina (VA) and myocardial bridges is a rare finding. We describe a case of VA with recurrent coronary spasm triggered by different stimuli at the site of a myocardial bridge. The interplay of endothelial dysfunction, coronary vasoconstriction and myocardial bridging was detected by intracoronary acetylcholine test and IVUS. We speculate that mechanical stimulation at the bridge site caused endothelial dysfunction and enhanced local susceptibility to vasoconstrictor stimuli. Variant angina should always be suspected in cases of ST-elevation acute coronary syndrome without any significant angiographic coronary stenosis. PMID- 22041366 TI - A case of carbon monoxide poisoning presenting with supraventricular tachycardia. AB - Carbon monoxide intoxication is one of the most common types of poisoning in the world. Cardiac manifestations after exposure to carbon monoxide including myocardial ischemia, heart failure and arrhythmias have been reported. A 17-year old woman was admitted to the emergency service with the complaints of palpitation, headache and nausea. Electrocardiogram revealed supraventricular tachycardia. The arterial blood gas analysis was normal. Her carboxyhemoglobin level was 19% and oxygen treatment was started promptly. Echocardiographic examination demonstrated normal cardiac function. To the best of our knowledge, this case report is the first carbon monoxide intoxication case in the literature presenting with supraventricular tachycardia attack. PMID- 22041367 TI - Bleeding from the small intestine and aortic regurgitation in Noonan syndrome. AB - A 62-year-old man was admitted to our hospital because of melena. On admission physical examination revealed that he had typical features of Noonan syndrome (NS). Investigation via upper endoscopy with the single balloon demonstrated oozing from the small intestine. Bleeding sometimes occurs in patients with NS. We speculated that coagulation defects or vascular malformations might have been present at the first visit in this case. However, coagulation function was normal. By upper endoscopy with the single balloon we clearly revealed the angioectasia in the small intestine. This case documents the first association among NS, aortic regurgitation and angioectasia in the small intestine. PMID- 22041368 TI - Plasmablastic extramedullary plasmacytoma associated with Epstein-Barr virus arising in an immunocompetent patient with multiple myeloma. AB - We encountered a case of plasmablastic extramedullary plasmacytoma with multiple myeloma. Histological findings revealed that the extramedullary plasmacytoma of this patient was of the plasmablastic type, which was positive for lambda-stain and EBV-encoded RNA. In contrast, bone marrow aspiration demonstrated a common type multiple myeloma, which was positive for lambda-stain and negative for EBV encoded RNA. This was a rare case of plasmablastic extramedullary plasmacytoma associated with Epstein-Barr virus arising in an immunocompetent patient with multiple myeloma. PMID- 22041369 TI - Long-term efficacy of trilostane for Cushing's syndrome due to adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia. AB - A 66-year-old man with Cushing's syndrome due to adrenocorticotropin-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) was treated for 7 years with trilostane, a 3beta-hydroxysteroid dehydrogenase inhibitor. Administration of trilostane reduced the serum cortisol level to around the upper limit of normal for 7 years, and symptoms of excessive glucocorticoid production (such as moon face and obesity) were gradually improved. On the other hand, the size of both adrenal glands gradually increased despite treatment with trilostane. Though trilostane therapy could not prevent adrenal growth, it did suppress cortisol secretion over the long term, so it might be a reasonable option for AIMAH in addition to adrenalectomy. PMID- 22041370 TI - A case of consciousness disturbance resulting from severe hypothyroidism due to chronic thyroiditis and excess iodine absorption. AB - An 82-year-old Japanese man had consciousness disturbance due to severe hypothyroidism triggered by percutaneous absorption of iodine from an iodine containing ointment used in diabetic gangrene treatment. Laboratory data revealed extremely high urinary iodine concentrations, and chronic thyroiditis-induced hypothyroidism. Excess iodine intake can also cause hypothyroidism. It was unlikely that iodine intoxication or Hashimoto's encephalopathy had caused the consciousness disturbance. The patient regained consciousness after discontinuing the use of the ointment and commencing thyroid hormone therapy. We conclude that consciousness disturbance resulted from severe hypothyroidism caused by chronic thyroiditis and excess iodine absorption. PMID- 22041371 TI - An exceedingly rare cause of secondary hypertension: bilateral renal artery dissection possibly secondary to extracorporeal shock-wave lithotripsy (ESWL). AB - Extracorporeal shock-wave lithotripsy (ESWL) is an effective and relatively non invasive treatment modality for ureteral or renal calculi. Although it has been accepted as a safe procedure, minor and major complications have been reported after ESWL. Spontaneous renal artery dissection (SRAD) is a rare and usually misdiagnosed condition because of non-specific presentation of the patients. Depending on the severity of the extent of the dissection non-operative or surgical treatment modalities could be performed. We represent a patient with complaints of bilateral flank pain, hematuria and hypertensive urgency who was diagnosed as having bilateral SRAD possibly secondary to ESWL and chronic hypertension. PMID- 22041372 TI - A case of adult T cell leukemia/lymphoma presenting as severe tracheal stenosis. AB - A 57-year-old woman was referred to our hospital for further examination of a tracheal stenosis shown on computed tomography findings. Bronchoscopy revealed multiple protruding tumors in the lumen of the trachea. Cytological findings of the cell block material from pleural effusion indicated that the T-cell lymphoma was composed of pleomorphic lymphoid cells. Serum human T-cell leukemia virus type 1 antibody was positive and supported the clinical diagnosis of ATLL. Systemic chemotherapy induced the remarkable improvement of the lesions, the infiltrative lung shadow and the soft tissue neoplasm. We report a rare case of adult T cell leukemia/lymphoma (ATLL) with endobronchial involvement. PMID- 22041373 TI - Iliopsoas hematoma in Gaucher's disease. AB - Gaucher's disease is an autosomal recessive inherited disease characterized by oraganomegaly, cytopenia and bone destruction. Clotting disorders and platelet dysfunctions are described. We report the case of a 22-year-old man who presented subacute groin pain due to spontaneous iliopsoas hematoma. Laboratory investigations found moderate thrombocytopenia, normal coagulation factor activities and unspecific platelet function test disturbances. His spleen was moderately enlarged and no significant bone lesions were found. Iliopsoas hematoma is a rare complication in Gaucher's disease and should be included in the differential diagnosis of pain localized to the groin-hip area, which could rather evoke hip osteonecrosis in this context. PMID- 22041374 TI - A case of myeloid sarcoma with correlation to JAK2V617F mutation, complicated by myelofibrosis and secondary acute myeloid leukemia. AB - The activating mutation of JAK2, V617F, has been found as a frequent mutation in myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). This mutation is observed not only in MPNs, but also in chronic myelomonocytic leukemia, myelodysplastic syndrome and acute myeloid leukemia (AML). We report a case of myeloid sarcoma and myelofibrosis, followed by secondary AML, with detection of homozygous JAK2 V617F mutation. This report describes the first case of myeloid sarcoma with JAK2 V617F mutation and implication of its progression to AML. PMID- 22041376 TI - Double-hit lymphoma with t(8;14)(q24;q32) and t(12;14)(q24;q32) chromosomal translocations. AB - A 50-year-old man presented with an ileocecal tumor and a large amount of ascites. Lymphoma cells obtained from the ascitic fluid were CD10(+), CD20(+), CD38(+), HLA-DR(+), BCL6(-), MUM1/IRF4(+), BCL2(+), and immunoglobulin u/gamma(+). The karyotype determined by G-banding and spectral karyotyping was 46, XY, der(3)t(1;3)(q12;p12), -4, +7, t(8;14)(q24;q32), t(12;14)(q24;q32), der(17)t(4;17)(q21;p11). Fluorescence in situ hybridization disclosed that 93% of interphase cells were positive for the c-MYC and immunoglobulin heavy chain gene fusion. The patient was treated with intensive chemo-immunotherapy, resulting in a complete response. The t(8;14)-t(12;14) double-hit may have generated molecular abnormalities analogous to those of a previously cloned three-way translocation t(8;12;14). PMID- 22041375 TI - Successful treatment of immunoglobulin D myeloma by bortezomib and dexamethasone therapy. AB - Immunoglobulin D (IgD) myeloma is a rare subtype and it is widely accepted as an aggressive disease. Here, we report a 66-year-old woman with IgD myeloma who had anemia, lumbago, multiple osteolytic lesions and hypercalcemia. The patient refused a blood transfusion because of her beliefs, so we administered bortezomib and dexamethasone (BD) after high-dose dexamethasone therapy. Marked improvement of anemia and elevated serum alkaline phosphatase levels was recognized. After 5 cycles of BD therapy, the patient achieved a stringent complete response according to International Myeloma Working Group Response Criteria. BD therapy might be a feasible and useful treatment option for IgD myeloma. PMID- 22041377 TI - A case of late onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency manifesting as recurrent rhabdomyolysis and acute renal failure. AB - We report an adult case of late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD) characterized by episodic recurrent rhabdomyolysis and acute renal failure after the age of 46. Muscle biopsy revealed lipid storage myopathy and the finding of serum acylcarnitine and urine organic acid analyses were consistent with MADD. A compound heterozygous mutation was identified in the electron-transferring-flavoprotein dehydrogenase (ETFDH) gene, including a novel missense mutation, which confirmed the diagnosis of MADD. After administration of riboflavin and L-carnitine, the muscle weakness and fatigability gradually improved. Acylcarnitine and urine organic acid were also normalized after supplementation. Thus, MADD should be included in one of the differential diagnoses for adult recurrent rhabdomyolysis. Gene analysis is useful to confirm the diagnosis, and early diagnosis is important because riboflavin treatment has been effective in a significant number of patients with MADD. PMID- 22041378 TI - Systemic lupus erythematosus complicated with acute myocardial infarction and ischemic colitis. AB - Acute myocardial infarction (AMI) is one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Ischemic colitis, mainly caused by intestinal vasculitis, is also one of the most serious, but uncommon, complications in SLE patients. "SLE vasculitis" simultaneously involving cardiac and gastrointestinal vessels has yet to be reported. This is the first report of SLE accompanying AMI, ischemic colitis and perforation of the digestive tract possibly due to SLE vasculitis, which was dramatically improved by treatment with high-dose glucocorticoid. PMID- 22041380 TI - Pseudoaneurysm with candidal infection after renal transplantation. PMID- 22041379 TI - Scrub typhus-induced serious gastric ulcer bleeding. AB - A 67-year-old woman presented with melena and general weakness. Upper gastrointestinal (GI) endoscopy revealed multiple ulcers and projectile bleeding in the stomach. She also complained of a 10-day history of a fever and was diagnosed with scrub typhus based on a positive result of the eschar polymerase chain reaction (PCR) testing. She fully recovered with endoscopic hemostasis, and administration of minocycline and omeprazole. In a patient with GI manifestations, scrub typhus, a condition with pathologically systemic vasculitis, should be considered in the possible background in endemic areas. The eschar PCR testing is a rapid and useful diagnostic tool to identify a specific strain. PMID- 22041381 TI - Esophagopericardial fistula with pyopneumopericardium secondary to esophageal carcinoma. PMID- 22041382 TI - Three-dimensional transesophageal echocardiography of P2 chordae tendinae rupture. PMID- 22041383 TI - Trabecular meshwork at the left ventricular apex. PMID- 22041384 TI - Giant pelvic calcification. PMID- 22041385 TI - Salmonella septicemia with iliac mycotic aneurysm and spondylitis. PMID- 22041386 TI - Respiratory failure and coma in an international traveler. PMID- 22041387 TI - Massive brain calcifications associated with vitamin D deficiency. PMID- 22041388 TI - Autosomal dominant osteopetrosis type II. PMID- 22041389 TI - Reversible "brain atrophy" in anti-NMDA receptor encephalitis. PMID- 22041390 TI - Hypoglycemic white matter lesion along the pyramidal tracts. PMID- 22041391 TI - Isolated hypoglossal nerve palsy caused by neurovascular compression. PMID- 22041392 TI - Low-dose tacrolimus with methotrexate repairs rheumatoid fingers. PMID- 22041393 TI - Ecthyma on the forehead: rare condition in the community setting. PMID- 22041394 TI - A case of idiopathic harlequin syndrome. PMID- 22041395 TI - Ovarian inguinal hernia in an elderly female. PMID- 22041396 TI - Renal infarction: a delayed complication of cardiac catheterization. PMID- 22041397 TI - Vasculitis in a patient with hairy cell leukemia. PMID- 22041398 TI - Staghorn blood clot. PMID- 22041399 TI - Is culture necessary before first-line treatment for Helicobacter pylori infection? PMID- 22041401 TI - Lophomonas misidentification in bronchoalveolar lavages. PMID- 22041403 TI - The spider-man principle. PMID- 22041404 TI - Composites and amalgam. PMID- 22041406 TI - Ethical referrals. PMID- 22041408 TI - Oral HPV. PMID- 22041409 TI - Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs. AB - BACKGROUND: This narrative review of osteonecrosis of the jaw in patients with low bone mass receiving treatment with antiresorptive agents is based on an appraisal of the literature by an advisory committee of the American Dental Association Council on Scientific Affairs. It updates the committee's 2008 advisory statement. METHODS: The authors searched MEDLINE for literature published between May 2008 (the end date of the last search) and February 2011. RESULTS: This report contains recommendations based on the findings of the literature search and on expert opinion that relate to general dentistry; periodontal disease management; implant placement and maintenance; oral and maxillofacial surgery; endodontics; restorative dentistry and prosthodontics; orthodontics; and C-terminal telopeptide testing and drug holidays. CONCLUSIONS: The highest reliable estimate of antiresorptive agent-induced osteonecrosis of the jaw (ARONJ) prevalence is approximately 0.10 percent. Osteoporosis is responsible for considerable morbidity and mortality. Therefore, the benefit provided by antiresorptive therapy outweighs the low risk of developing osteonecrosis of the jaw. CLINICAL IMPLICATIONS: An oral health program consisting of sound hygiene practices and regular dental care may be the optimal approach for lowering ARONJ risk. No validated diagnostic technique exists to determine which patients are at increased risk of developing ARONJ. Discontinuing bisphosphonate therapy may not lower the risk but may have a negative effect on low-bone-mass-treatment outcomes. PMID- 22041410 TI - A retrospective review of clinical international normalized ratio results and their implications. AB - BACKGROUND: Warfarin is a key element in therapy for atrial fibrillation, deep venous thrombosis (DVT), stroke (cerebrovascular accident) and cardiac valve replacement. Often, patients' warfarin blood levels are not tightly controlled with regard to accepted therapeutic ranges, by virtue of the drug's unpredictable nature. METHODS: The authors searched 16,017 active clinical charts for active patients of record from the three campuses of the School of Dentistry, Marquette University (MU), Milwaukee, for the years 2009 and 2010. Dental records of 315 patients contained entries including "INR," the abbreviation for the term "international normalized ratio." Only 247 of those records contained an indication of whether the patient's INR values were within therapeutic range. The authors found that 1.96 percent of the total MU dental clinic patient population had a history of warfarin use. RESULTS: When the authors compared the INR values for patients with diagnoses of atrial fibrillation, DVT, stroke and cardiac valve replacement, they found that INR values for 107 of the 247 patients (43.3 percent) were not within therapeutic range for the respective diagnoses. For example, only 50 percent of the patients being treated for atrial fibrillation presented themselves for surgical dental treatment while their INR values were in tight control. CONCLUSION: The INR values for a significant number of dental patients are not within the therapeutic range for their medical conditions. These patients need to seek follow-up care from their medical care providers. CLINICAL IMPLICATIONS: Screening for INR in the dental office-especially before invasive dental treatment such as periodontal surgery, tooth extraction and dental implant placement-can help prevent postoperative complications. It also can aid the clinician in evaluating whether a patient's INR is within therapeutic range and, subsequently, whether the patient's physician needs to adjust the warfarin dosage. PMID- 22041411 TI - Treating a maxillary midline diastema in adult patients: a general dentist's perspective. AB - BACKGROUND: A maxillary midline diastema (MMD) often is a primary concern of patients during a dental consultation. Although an MMD can be transient owing to the developing dentition and, thus, requires no active treatment, management of MMDs in the permanent dentition requires a detailed examination and appropriate care. CASE DESCRIPTION: . The authors present five cases of MMDs in adults to illustrate a range of restorative and orthodontic options. In the first case, the clinician used resin-based composite buildup to close an MMD resulting from small teeth and generalized spacing in the dental arch. In the second case, the clinician placed porcelain veneers to treat an MMD in a patient with discolored dentition. In the third case, the clinician fitted a removable appliance to close an MMD by tipping the incisors palatally. In the fourth case, the clinician fitted a sectional fixed appliance to promote mesial bodily movement of the incisors. In the fifth case, the clinician placed a full-arch fixed appliance to treat an MMD caused by tilted incisors. CONCLUSIONS: and CLINICAL IMPLICATIONS: Effective treatment requires an accurate diagnosis and appropriate intervention. General dentists can perform a range of restorative and orthodontic treatments in appropriate clinical situations to address patients' concerns. PMID- 22041412 TI - Gingival enlargement. PMID- 22041413 TI - Controlling bacterial contamination of dental impression guns. AB - BACKGROUND: Dental impression material handgun cartridge dispensers are contaminated easily during clinical use. The authors attempted to quantify contamination by bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), of impression guns used in an academic dental clinic after five infection prevention protocols were followed. METHODS: The authors obtained samples from four commercially available impression guns at four specific sites (button, handle, latch, trigger) after routine clinical use, disinfection, steam sterilization (also known as autoclaving), steam sterilization followed by use of plastic impression gun covers and steam sterilization followed by use of plastic impression gun covers and disinfection. RESULTS: The authors found that after routine clinical use, bacteria-including MRSA-heavily contaminated the impression guns. After the impression guns underwent disinfection, there was a 6 percent decrease in bacterial counts. The use of steam sterilization achieved sterility without harming the impression guns. Use of steam-sterilized impression guns with plastic impression gun covers decreased bacterial isolates by approximately 60 percent. Use of steam-sterilized impression guns plus covers and disinfection resulted in an approximately 95 percent reduction in contamination. CONCLUSIONS: The use of common infection-prevention methods appears to reduce the bacterial counts, including those of MRSA. Bacterial contamination was lowest after steam sterilization, followed by the use of plastic impression gun covers and disinfection. CLINICAL IMPLICATIONS: Use of contaminated impression guns on successive patients could increase the risk of causing cross-transmission of disease. The use of sterilization, plus plastic impression gun covers and disinfection, for impression guns after each use could be an effective and practical infection-control method for dental practices. PMID- 22041414 TI - Knowledge and beliefs regarding oral health among pregnant women. AB - BACKGROUND: Racial or ethnic and economic disparities exist in terms of oral diseases among pregnant women and children. The authors hypothesized that women of a racial or ethnic minority have less oral health knowledge than do women not of a racial or ethnic minority. Therefore, the authors conducted a study to assess and compare maternal oral health knowledge and beliefs and to determine if maternal race and ethnicity or other maternal factors contributed to women's knowledge or beliefs. METHODS: The authors administered a written oral health questionnaire to pregnant women. The authors calculated the participants' knowledge and belief scores on the basis of correct answers or answers supporting positive oral health behaviors. They conducted multivariable analysis of variance to assess associations between oral health knowledge and belief scores and characteristics. RESULTS: The authors enrolled 615 women in the study, and 599 (97.4 percent) completed the questionnaire. Of 599 participants, 573 (95.7 percent) knew that sugar intake is associated with caries. Almost one-half (295 participants [49.2 percent]) did not know that caries and periodontal disease are oral infections. Median (interquartile range) knowledge and belief scores were 6.0 (5.5-7.0) and 6.0 (5.0-7.0), respectively. Hispanic women had median (interquartile range) knowledge and belief scores significantly lower than those of white or African American women (6.0 [4.0-7.0] versus 7.0 [6.0-7.0] versus 7.0 [6.0-7.0], respectively [P < .001]; and 5.0 [4.0-6.0] versus 6.0 [5.0-7.0] versus 6.0 [5.0-7.0], respectively [P < .001]). Multivariable analysis of variance results showed that being of Hispanic ethnicity was associated significantly with a lower knowledge score, and that an education level of eighth grade or less was associated significantly with a lower belief score. CONCLUSIONS: Pregnant women have some oral health knowledge. Knowledge varied according to maternal race or ethnicity, and beliefs varied according to maternal education. Including oral health education as a part of prenatal care may improve knowledge regarding the importance of oral health among vulnerable pregnant women, thereby improving their oral health and that of their children. CLINICAL IMPLICATIONS: Including oral health education as a part of prenatal care should be considered. PMID- 22041416 TI - Modest improvement in temporomandibular disorder-related pain associated with use of hard stabilization appliances compared with use of nonoccluding appliances or no therapy. PMID- 22041415 TI - Prenatal exposure to dental amalgam: evidence from the Seychelles Child Development Study main cohort. AB - BACKGROUND: Dental amalgams contain approximately 50 percent metallic mercury and emit mercury vapor during the life of the restoration. Controversy surrounds whether fetal exposure to mercury vapor resulting from maternal dental amalgam restorations has neurodevelopmental consequences. METHODS: The authors determined maternal amalgam restoration status during gestation (prenatal exposure to mercury vapor [Hg(0)]) retrospectively in 587 mother-child pairs enrolled in the Seychelles Child Development Study, a prospective longitudinal cohort study of the effects of prenatal and recent postnatal methylmercury (MeHg) exposure on neurodevelopment. They examined covariate-adjusted associations between prenatal maternal amalgam restoration status and the results of six age-appropriate neurodevelopmental tests administered at age 66 months. The authors fit the models without and with adjustment for prenatal and recent postnatal MeHg exposure metrics. RESULTS: The mean number of maternal amalgam restorations present during gestation was 5.1 surfaces (range, 1-22) in the 42.4 percent of mothers who had amalgam restorations. The authors found no significant adverse associations between the number of amalgam surfaces present during gestation and any of the six outcomes, with or without adjustment for prenatal and postnatal MeHg exposure. Results of analyses with the secondary metric, prenatal amalgam occlusal point scores, showed an adverse association in boys only on a letter- and word-identification subtest of a frequently used test of scholastic achievement, whereas girls scored better on several other tests with increasing exposure. CONCLUSIONS: This study's results provide no support for the hypothesis that prenatal Hg(0) exposure arising from maternal dental amalgam restorations results in neurobehavioral consequences in the child. These findings require confirmation from a prospective study of coexposure to MeHg and Hg(0). PMID- 22041417 TI - The reality of competition. PMID- 22041418 TI - What are my obligations when purchasing new technologies? PMID- 22041419 TI - Osteoporosis medications and your dental health. PMID- 22041420 TI - [Pattern recognition receptors]. AB - Immunity is based on self/nonself discrimination. In vertebrates, two major systems, innate and adaptive immune systems, constitute host defense against invading microbes. Adaptive immunity is characterized by specific immune responses through B- or T-cell antigen receptors that are generated by somatic recombination, whereas nonspecific responses to microbes had been accentuated in innate immunity. However, the discovery of pattern recognition receptors (PRRs) that are encoded in the germ-line, including Toll-like receptors, RIG-I-like receptors, NOD-like receptors and AIM2-like receptors, advanced our understanding of a mechanism for innate immune recognition. These types of PRR recognize pathogen- or damage-associated molecular patterns (PAMPs or DAMPs) during infection or tissue damage, and commonly evoke the downstream gene induction programme, such as expression of type I interferons, inflammatory cytokines and chemokines. Dysregulation of PRR-triggered signal activation leads to pathologic inflammatory responses. In this regard, it has been shown that many of "autoinflammatory diseases", recently defined clinical entity, have putatively causative mutations in the genes that encode PRRs or their signaling mediators. In this review article, we describe recent overview of PRRs as innate sensors and update knowledge of "autoinflammatory diseases" particularly by focusing on their association with innate signaling. PMID- 22041421 TI - ["The inflammasomes"]. AB - Inflammation is a host adaptational response to cell injury caused by various exogenous and endogenous stimuli. IL-1beta, which is an important proinflammatory cytokine secreted at the site of cellular injury, plays an important role in inflammation. Inflammasome is an intracellular multi-protein complex that mediates caspase-1-dependent processing of IL-1beta. In this review, inflammasome function and its dysregulation are discussed in relation to autoinflammatory diseases. PMID- 22041422 TI - [Clinical aspects of Familial Mediterranean fever]. AB - Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent and short duration (1-3 days) of fever, and serositis. Based on the nationwide survey of FMF in Japan, the estimated number of Japanese FMF patients is about three hundred. High grade fever was observed in 95.5%, chest pain in 35.8% abdominal pain in 62.7% and arthritis in 31.3% among Japanese FMF patients. AA amyloidosis was confirmed in 5 patients (3.7%). Colchicine was effective in 91.8% of Japanese FMF patients. A significant number of FMF patients exist in Japan, and early diagnosis and treatments should be required to prevent AA amyloidosis. PMID- 22041423 TI - [Progress in classification and treatment for TNF receptor-associated periodic syndrome]. AB - TNF receptor-associated periodic syndrome (TRAPS) is an autosomal dominant autoinflammatory disorder characterized by recurrent febrile attacks. TRAPS is associated with mutation in the gene encoding TNF Receptor I (TNFRI) and seven mutations have been reported in Japan. Molecular modeling experiments indicate that the mutant TNFRI accumulates intracellularly in the endoplasmic reticulum due to misfolding and activates MAP kinase (MAPK) through induction of mitochondrial reactive oxygen species production. MAPK activation is further enhanced by the stimulation through toll-like receptor, resulting in the enhanced proinflammatory cytokine production. Febrile attacks last 21 days on average and occur every one to several months. Myalgia, erythematous macular rash, abdominal pain, conjunctivitis, periorbital edema, chest pain and arthralgia are commonly seen during the attacks. Glucocorticoid is effective in decreasing the severity and duration of the febrile attacks. Soluble TNF receptor etanercept, IL-1 receptor antagonist Anakinra(TM) and IL-6 receptor antagonist tocilizumab are effective in some patients. Japanese study group of TRAPS conducted national survey to make new diagnostic criteria in 2010. PMID- 22041424 TI - [CAPS: cryopyrin-associated periodic syndrome]. AB - Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory syndrome caused by heterozygous mutations of NLRP3 gene. CAPS consists of three phenotypically similar but distinct syndromes: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome and CINCA syndrome. Among them, FCAS shows the mildest phenotype while CINCA is the severest. Common symptoms include sporadic or cold-induced nonpruritic urticarial rash and fever. Severe cases suffers from deafness, meningitis, articular contracture and secondary amyloidosis. Gain-of-function mutations of NLRP3 causes excessive production of a potent proinflammatory cytokine IL-1beta, thereby evokes autoinflammatory symptoms of CAPS. Recent advances of anti-IL-1 therapy dramatically improved the prognosis of CAPS. Currently three anti-IL-1 medicines are available, and all of them significantly improved clinical symptoms of CAPS patients. Although long term observation is still needed, the molecular-targeted therapy has opened up a new opportunity for managing CAPS. PMID- 22041425 TI - [Early-onset sarcoidosis/Blau syndrome]. AB - Familial Blau syndrome and sporadic early-onset sarcoidosis (EOS) are both systemic granulomatous diseases evoked by the spontaneous activation of mutated NOD2. In Japan, the R334W amino acid substitution is more frequently identified, whereas the R334Q mutation is rare and, in contrast to western countries where disease causing mutations are typically hereditary, most Japanese cases derive from sporadic mutations. Recently, a case with a six-base deletion in the NOD2 gene was reported. This Blau syndrome/EOS patient presented with the unpainful soft swelling of the dorsal side of the wrist and ankles, as well as flexion contracture at the proximal interphalangeal joint that gradually appeared during their clinical course. These features are useful for the differential diagnosis of Blau syndrome/EOS from juvenile idiopathic arthritis. Owing to their characteristic clinical symptoms, Blau and EOS patients can be identified earlier if medical experts become more acquainted with these distinctions. Even though specific treatment based on pathophysiologic mechanism has not been explored yet, early diagnosis will prevent the progression to severe impairment, which can severely affect patients' lives. PMID- 22041426 TI - [Hyperimmunoglobulinemia D and periodic fever syndrome]. AB - Hyperimmunogloblinemia D and periodic fever syndrome (HIDS) is inherited autoinflammatory syndrome caused by deficiency of the mevalonate kinase (MK), which is involved in metabolism of cholesterol. The disease is characterized as periodic fever from early infancy accompanied by elevated serum C-reactive protein. Since clinical symptoms such as abdominal symptom, skin rash, and arthritis are common to other autoinflammatory disease, the diagnosis of HIDS during clinical work is difficult for the physicians without suspicion of HIDS for infants suffering from fever of unknown origin. Moreover, serum IgD levels are not high during infancy conflicting to the name of the disease, which is often misunderstood in the clinicians. Thus, the diagnosis of HIDS in Japan is bothering, depending on the lack of correct recognition of the disease and on the lack of commercially available examination for the disease. It is important for clinicians, especially pediatricians to update current knowledge about HIDS and to learn the appropriate way to the definitive diagnosis of HIDS, because HIDS patients exist also in Japan and the specific therapies for HIDS would be developed in the near future. PMID- 22041427 TI - [Nakajo-Nishimura syndrome]. AB - Nakajo-Nishimura syndrome (NNS) (MIM256040, ORPHA2615) is a distinct inherited inflammatory and wasting disease, which usually begins in early infancy with a pernio-like rash. The patients develop periodic high fever and nodular erythema like eruptions, and gradually progress lipomuscular atrophy in the upper body, mainly the face and the upper extremities, to show the characteristic long clubbed fingers with joint contractures. So far about 30 cases have been reported from Kansai, especially Wakayama and Osaka, Tohoku and Kanto areas. In addition to 10 cases in Kansai area, which have been confirmed to be alive by national surveillance, an infant case has newly been discovered in Wakayama and more cases will be added. Although cause of the disease has long been undefined, a homozygous mutation of the PSMB8 gene, which encodes the beta5i subunit of immunoproteasome, has been identified by homozygosity mapping. By analyses of the patients-derived cells and tissues, it has been suggested that accumulation of ubiquitinated and oxidated proteins due to deficiency of proteasome activities cause hyperactivation of p38 MAPK and overproduction of IL-6. Similar diseases with PSMB8 mutations have recently been reported from Europe and the U.S.A., and therefore, it is becoming clear that proteasome deficiency syndromes are globally distributed as a new category of the autoinflammatory diseases. PMID- 22041428 TI - [Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome]. AB - Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is a non-hereditary autoinflammatory disease, characterized by relatively regular recurrence of febrile episodes of 3-6 days duration, accompanied by aphthous stomatitis, pharyngitis/tonsillitis, and/or cervical adenititis. It is considered to be the most common periodic fever syndrome in Japan. Although no responsible gene is identified, some genetic factors may confer the predisposition toward this disorder. Important differential diagnosis includes hereditary periodic syndromes and cyclic neutropenia. Although its etiology is still to be elucidated, a recent study suggested an environmentally triggered activation of complement and IL-1beta/IL-18 during PFAPA syndrome flares, with induction of Th1 chemokines and subsequent retention of activated T cells in peripheral tissues. This study also demonstrated the possibility that IP-10/CXCL10 might serve as a potential biomarker to differentiate PFAPA syndrome from other periodic fever syndromes. Therapeutic strategy for PFAPA syndrome has not been well established. Recent advances in the understating of etiology and pathophysiology might lead to re-evaluation of recent therapeutic options and/or development of new treatment. PMID- 22041429 TI - [Behcet's disease from the aspect of autoinflammatory disease]. AB - Behcet's disease is a systemic inflammatory disease presented with recurrent oral aphtha, cutaneous manifestations, uveitis, and genital ulcer. The etiology of Behcet's disease is still unknown, but both genetic background and environmental factors are thought to be important in the pathogenesis of Behcet's disease. Behcet's disease has long been regarded as a Th1 type autoimmune disease, because of the association with HLA-B51 and hyperreactivity against streptococcal antigen. However, it was recently found that Behcet's disease and autoinflammatory diseases share several clinical features. Furthermore, increased activity of neutrophils and elevated levels of interleukin-1beta are observed in both Behcet's disease and autoinflammatory diseases. The relationship between Behcet's disease and autoinflammatory diseases, especially Familial Mediterranean fever, is speculated, because both diseases are prevalent in the Mediterranean basin and treated with colchicine. Genetic researches on Behcet's disease and FMF suggest that the MEFV gene mutated in Familial Mediterranean fever is a probable susceptibility gene for Behcet's disease. Although many observations suggest that Behcet's disease might be autoinflammatory, there is evidence implying autoimmune pathogenesis of Behcet's disease. For example, some symptoms of Behcet's disease is treated with T cell suppressing agents. Recent data suggest that a novel subset of T cells, Th17, plays a crucial role in pathogenesis of Behcet's disease, and genome-wide association researches verified it. IL-17, which is the secreted from of Th17 activates neutrophils. Hence, IL-17 might cause the symptoms resembling autoinflammatory diseases. Recently, Anti-IL-1 treatment proved to be effective and other susceptibility genes are being investigated. These new findings will shed light on the long-sought pathogenesis of Behcet's disease. PMID- 22041430 TI - [Pneumocystis pneumonia developed in two patients with rheumatoid arthritis during treatment of adalimumab]. AB - While tumor necrosis factor (TNF) inhibitors have dramatically improved the clinical outcomes of rheumatoid arthritis (RA) in recent years, infectious complications are a serious concern. Adalimumab (ADA) is a newly-developed human monoclonal antibody against TNF-alpha. Here we report 2 cases of pneumocystis pneumonia (PCP) which developed in RA patients during ADA therapy. One patient is a 66-year-old woman who had a history of RA for 6 months. The patient was given ADA at 40 mg biweekly for her active arthritis which had been refractory to 6 mg/week of methotrexate (MTX), and 5 mg/day of prednisolone (PSL). One hundred and six days later, she was admitted to our hospital because of fever, cough, and dyspnea. Another patient is a 62-year-old man who had a history of RA for 3 years. Since his arthritis was so active even under the treatment with MTX (8 mg/week) and PSL (15 mg/day), the patient started to be given ADA at 40 mg biweekly. After 28 days, the patient was admitted to the hospital because of dyspnea. Chest roentgenogram and computed tomography revealed interstitial pneumonia in both patients. Beta-D-glucan levels were so high in their serum suggesting the diagnosis of PCP, which was confirmed by the detection of Pneumocystis jirovecii DNA in the sputa by polymerase chain reaction. The patients were immediately treated with sulfamethoxazole/trimethoprim and high dose prednisolone, which successfully improved pneumonia, and they were discharged from the hospital on the 8(th) and 16(th) day, respectively. PCR and beta-D-glucan were useful for the early diagnosis of PCP and lead to the timely induction of adequate treatment and the rescue of these patients. PMID- 22041431 TI - [Simultaneous relapse of Basedow's disease in a patient with adult-onset Still's disease]. AB - This report describes a 50-year-old woman with coexisting Basedow's disease and adult-onset Still's disease (AOSD) that relapsed simultaneously. She was diagnosed with Basedow's disease in 1999, and treatment with antithyroid agents was started. However, the treatment was soon stopped because of severe side effects. A partial thyroidectomy was performed and the thyroid function stayed well-controlled after the surgery. In August 2007, she was admitted to our hospital with fever, a sore throat, skin rashes, arthritis and leukocytosis, and was diagnosed with AOSD. At the same time, her laboratory data revealed decreased serum TSH and elevated serum free T4, suggesting a relapse of Basedow's disease. After initiation of steroid pulse therapy accompanied by oral prednisolone, both diseases improved significantly. Prednisolone was gradually reduced, and the disease activity remained in remission. Immediately after prednisolone reached 3 mg/day in November 2009, both diseases relapsed. Prednisolone was increased to 30 mg/day, and the diseases became well-controlled again. In this case, Basedow's disease was aggravated when AOSD was in the active stage. Literature searches revealed five previously reported cases with coexisting Basedow's disease and AOSD. In four of the six cases, including our case, both diseases were activated simultaneously. AOSD in the active stage is known to cause hypercytokinemia and immunological derangement. Our case indicated that the pathogenesis of AOSD might lead to relapse of coexisting Basedow's disease. PMID- 22041432 TI - [Case of Fusobacterium necrophorum sepsis (Lemierre's syndrome) with pulmonary septic emboli and liver abscess]. AB - The present article documents a case of Fusobacterium sepsis with a transient anticardiolipin antibody increase in an otherwise healthy 24-year-old patient. He was presented to the emergency room with headache and fever. His temperature was 39.5 degrees C, laboratory results revealed a white blood count of 15.2*10(3)/MUl and C reactive protein 22.6 mg/dl. The patient was admitted. Chest X-ray showed the infiltrate in bilateral lower lung area. He received 400 mg of clarithromycin per day. His all symptoms did not change. On the 8(th) day in the hospital, the patient's antibiotics were switched to pazufloxacin. Chest and abdominal CT scan showed some irregular patchy nodules of around 1 cm in diameter in the bilateral lower lung fields and a round low density lesion 3 cm in diameter in the right upper segment (S8) in the liver. Blood culture revealed Fusobacterium necrophorum. On the 10(th) day, the antibacterial agent was changed from pazufloxacin to ampicillin sulbactam. On the 17(th) day, we added clindamycin. As a result his temperature gradually returned to normal. It is reported that the titer of anticardiolipin antibody increases in the sepsis patients caused by Fusobacterium necrophorum. As his symptoms disappeared, his titer of anticardiolipin antibody also decreased. So we considered he had a transient anticardiolipin titer increase. PMID- 22041433 TI - CYP2F2-generated metabolites, not styrene oxide, are a key event mediating the mode of action of styrene-induced mouse lung tumors. AB - Styrene induces lung tumors in mice but not in rats. Although metabolism of styrene to 7,8-styrene oxide (SO) by CYP2E1 has been suggested as a mediator of styrene toxicity, lung toxicity is not attenuated in CYP2E1 knockout mice. However, styrene and/or SO metabolism by mouse lung Clara cell-localized CYP2F2 to ring-oxidized cytotoxic metabolite(s) has been postulated as a key metabolic gateway responsible for both lung toxicity and possible tumorigenicity. To test this hypothesis, the lung toxicity of styrene and SO was evaluated in C57BL/6 (WT) and CYP2F2-/- knockout mice treated with styrene (400 mg/kg/day, gavage, or 200 or 400 mg/kg/day, ip) or S- or R-SO (200 mg/kg/day, ip) for 5 days. Styrene treated WT mice displayed significant necrosis and exfoliation of Clara cells, and cumulative BrdU-labeling index of S-phase cells was markedly increased in terminal bronchioles of WT mice exposed to styrene or S- or RSO. In contrast, Clara and terminal bronchiole cell toxicity was not observed in CYP2F2-/- mice exposed to either styrene or SO. This study clearly demonstrates that the mouse lung toxicity of both styrene and SO is critically dependent on metabolism by CYP2F2. Importantly, the human isoform of CYP2F, CYP2F1, is expressed at much lower levels and likely does not catalyze significant styrene metabolism, supporting the hypothesis that styrene-induced mouse lung tumors may not quantitatively, or possibly qualitatively, predict lung tumor potential in humans. PMID- 22041434 TI - Baclofen toxicity in patients with advanced nephropathy: proposal for new labeling. AB - BACKGROUND: Despite several reports in the literature of baclofen toxicity in patients with renal dysfunction, the drug is being used for many patients. METHODS: Herein we report a case of baclofen-induced encephalopathy in a patient with pre-end-stage renal disease and review the literature regarding the magnitude of baclofen toxicity in patients with renal insufficiency. A Medline search for studies in English was performed. Twenty-one case reports involving 41 patients (including our patient) were identified. RESULTS: The majority of patients were elderly (62.5% above 60 years) males (56.3%) on dialysis (62.9%). Neurotoxicities were almost always present at presentation. Manifestations of baclofen toxicity usually started 2-3 days after starting baclofen; however, periods as long as 16 weeks have been reported. The daily dose of baclofen ranged from 5 to 60 mg with a mean dose of 20 mg. Hemodialysis (HD) was the most common treatment modality used for drug elimination (65.7%). The recovery time ranged from 2 h in patients who received HD, to 8 days with conservative treatment. CONCLUSION: The literature does not mention a clear recommendation about baclofen safety and dose adjustment, or a minimum level of kidney function below which the drug should not be used. PMID- 22041435 TI - Endocrine orbitopathy: 11 years retrospective study and review of 102 patients & 196 orbits. AB - BACKGROUND: Endocrine Orbitopathy (EO) is the most frequent and important extrathyroidal stigma of Graves' disease. In the active stage of the orbitopathy fibrosis and hypertrophy of the extra-ocular muscles can lead to visual impairment and diplopia. In the stable phase of the disease surgical treatment by orbital expansion and/or orbital decompression can improve the quality of life and it is indicated for morpho-aesthetic and functional reasons. METHODS: From 1998 to 2009 a consecutive series of 131 patients (251 orbits) with endocrine orbitopathy underwent surgery by different techniques. The medical records of 102 patients (78%) and 196 orbits were available to be assessed retrospectively. Ninety-four patients had bilateral involvement of the orbits and eight unilateral. A total of 556 operations were performed. RESULTS: Mean pre-operative exophthalmos was 24.7 +/- 2.5 mm (max-min 20-34), mean post-operative exophthalmos was 21 +/- 1.8 mm (max-min 18-26), and mean differential exophthalmos was 3.9 +/- 1.7 mm (max-min 1-9). The reduction in exophthalmos after surgery had a mean value of 3.8 mm (min 1, max 9). Kaplan Meier algorithm demonstrates that intra-operative cortisone injection had an adverse effect on post-operative diplopia. CONCLUSIONS: The surgical technique used should be adapted to the individual patients' needs. In severe cases intraorbital fat removal and bony decompression can be and carried out in one surgical procedure. An integrated global approach by a multidisciplinary team is strongly recommended. Strabismus surgery is a significant part of the overall treatment. The Authors suggest general surgical guidelines and an algorithm of treatment in EO. PMID- 22041437 TI - [Case-control study on influence factors of birth defects]. AB - OBJECTIVE: To investigate the influence factors of birth defects. METHODS: The congenital malformational fetuses born from 13 week of gestation to 7 days after birth were selected as the study group between April 1st, 2009 and March 31st, 2010. The health born fetuses were set as control in the same period. Case control and the three-level of monitor network of birth defects were used in the study in the participating 75 hospitals (Qingdao Women and Children's Medical Center, Affiliated Hospital of Medical College Qingdao University, Qingdao Municipal Hospital, etc.). The study and control group's parents were interviewed by an uniformed questionnaire which was designed specially with influence factors of birth defects. RESULTS: (1) There are 466 congenital malformational fetuses in the total of 77 231 fetuses collected in 75 hospitals. The congenital malformational rate accounts for about 6.0340/00. The top six defect diseases were congenital heart disease (112 cases), total harelip (cleft lip; cleft lip with palate: 85 cases), polydactyly (53 cases), neural tube defects (38 cases), congenital hydrocephalus (37 cases) and limb reduction defect (27 cases) in turn, which amounts to 353 cases (54.48%, 353/648). (2) Their mother education level in the birth-defect group (25.6%) were significantly lower than that in control group (30.0%, P<0.05). (3) The rate of passive smoking, drinking, raising pets of the parents in birth-defect group were significantly higher than that in control group (P<0.05). (4) The rate of exposure to harmful chemical and physical factors of mothers in birth defects group (13.9% and 20.5%, respectively) was higher than that in control group (1.1% and 11.7%, respectively), the difference between which were significant (P<0.01). The rate of disease (34.3%), fever (13.1%), taking drugs (33.8%) in pregnancy period in birth defect group were higher than that in control group (13.5%, 1.5% and 9.9%, respectively), the difference between which were significant (P<0.01). The rate of bad moral irritation to the mother in pregnancy in birth defect group (11.3%) was significantly higher than that in control group (1.4%, P<0.01). (5) There were 19 cases (2.9%, 19/648) with family heredity medical history in birth defect group, but there were none in the control group, the difference between which were significant (P<0.01). There were 89 cases (13.7%, 89/648) with unusual birth history of their mothers in birth defect group, but there were 31 cases (4.8%, 31/650) in control group, the difference between which were significant (P<0.01). (6) Conditional Logistic Regression model was used for univalent and multivariate analysis. The results showed that main influence factors were identified as having important effect on birth defects, including mothers' exposure to harmful chemical factors (OR=13.46), disease (OR=3.37), taking drugs (OR=2.20), exposure to bad moral irritation (OR=5.44), food-choosy (OR=1.90), anemia (OR=1.52) in gestational period, polyembryony (OR=4.40), father drinking (OR=1.55). While it was protective factors to supplement microelements such as the calcium iron and nutrient, etc.in pregnancy period (OR=0.45). CONCLUSIONS: First, the main birth defects were congenital heart disease, total harelip(cleft lip; cleft lip with palate), polydactyly, neural tube defects, congenital hydrocephalus and limb reduction defect in turn. Second, the main influence factors identified as having important effect on birth defects were mothers' exposure to harmful chemical factors, ill, taking drugs, exposure to bad moral irritation, food-choosy, anemia in gestational period, polyembryony, father drinking. But it is protective factors to supplement microelements such as the calcium iron and nutrient, etc. in pregnancy period. Finally, it is the important part to prevent the birth defects by reducing and controlling dangerous factors in pregnancy period. PMID- 22041438 TI - [Comparison and analysis of different diagnostic criteria for peripartum cardiomyopathy]. AB - OBJECTIVE: To compare the differences and similarities between the diagnostic criteria of obstetrics and internal medicine in China with that of Hibbard for peripartum cardiomyopathy (PPCM). METHODS: From March 1995 to September 2009, a total of 49 patients were diagnosed as PPCM at the Peking University People's Hospital and the Fu Wai Hospital in Beijing, China. Obstetric diagnostic criteria was: PPCM was one of dilated cardiomyopathy, occurred during the third trimester of pregnancy through the 6th month postpartum, and without cardiovascular diseases before. Internal medicine diagnostic criteria was: PPCM was unexplained cardiomegaly and heart failure, occurred during the last month of pregnancy through the 5th month postpartum, and meet the echocardiographic criteria of dialated cardiomyopathy as follows:left ventricular end-diastolic dimension (LVEDd) greater than 5.0 cm; left ventricular ejection fraction (LVEF) less than 45%, and(or) left ventricular fractional shortening (LVFS) less than 30%; or LVEDd greater than 2.7 cm/body surface area (m2); or LVEDd>117% of age and body surface area predictive value. Hibbard diagnostic criteria was: All four of the following: (1) heart failure within last month of pregnancy and 5 months postpartum; (2) absence of prior heart disease; (3) no determinable cause; (4) strict echocardiographic indication of left ventricular dysfunction: LVEF less than 45%, and/or LVFS less than 30%, and LVEDd greater than 2.7 cm/m2. The compliance between obstetric and internal criteria with Hibbard criteria, and the reasons of incompliance between Chinese and international criteria were analyzed. RESULTS: Eight patients were diagnosed of PPCM by obstetricians according to Chinese obstetric criteria. Among them, 6 patients (6/8) did not meet Hibbard criteria.2 of the six did not reach the time regulated in the criteria. All of the six had other determinable causes for heart failure, and their echocardiographic results did not meet the diagnostic standard either. The other 41 patients were diagnosed of PPCM by physicians according to Chinese internal medicine criteria. Among them, 7 patients (17%) did not meet Hibbard criteria, 3 of the seven did not reach the time regulated in the criteria, and had other determinable causes for heart failure either.4 of the seven did not meet the echocardiographic standard part in the criteria. The Chinese internal medicine diagnostic criteria has a significant higher coincidence rate with Hibbard criteria, compared to Chinese obstetric criteria (83% vs. 25%; P<0.01). Among all 13 patients whose PPCM diagnosis did not meet Hibbard criteria, 5 cases did not reach the time regulated in the criteria, 9 cases had other determinable causes for heart failure, and 10 cases did not meet the echocardiographic standard part in the criteria. Preeclampsia was the most common determinable causes for heart failure, accounted for 7 cases. CONCLUSION: There is obvious difference between Chinese and Hibbard diagnostic criteria for PPCM, especially Chinese obstetric criteria. PMID- 22041439 TI - [Investigation on bone health conditions in 1637 aged women]. AB - OBJECTIVE: To investigate bone health conditions in 1637 aged women. METHODS: From May 2004 to October 2008, Bone mineral density (BMD) of 1637 women at age of more than 60 years old were measured by Hologic DephiA dual energy X-ray absorptiometry (DXEA) in Huadong hospital affiliated to Fudan University. All data were compared and analyzed among each group which will be divided by every ten years. Those women were divided into groups on 10 years range. BMD of lumbar vertebral and hip bone, fracture incidence and bone turnover marker were compared and analyzed. RESULTS: (1) BMD: at age of >=90, 80-89, 70-79, 60-69, BMD of the lumbar vertebral 2-4 (L2-4) values were (0.96+/-0.18), (0.90+/-0.20), (0.81+/ 0.16), (0.83+/-0.14) g/cm2, respectively. There were significantly increased BMD of lumbar of women at the age of 80-89 and >=90 year-old compared with those of 60-69 year-old (P<0.05). At age of >=90, 80-89, 70-79, 60-69 BMD of femur neck, Total, Torch, Ward's trianger were (0.60+/-0.11), (0.65+/-0.11), (0.47+/-0.09), (0.37+/-0.09) g/cm2; at age of 80-89 BMD of FN, Total, Torch, Ward's trianger were (0.57+/-0.10), (0.68+/-0.13), (0.48+/-0.11), (0.35+/-0.10) g/cm2; at age of 70-79 BMD of FN, Total, Torch, Ward's trianger were (0.57+/-0.10), (0.69+/-0.12), (0.49+/-0.10), (0.36+/-0.11) g/cm2; at age of 60-69 BMD of FN, Total, Torch, Ward's trianger were (0.63+/-0.10), (0.76+/-0.12), (0.54+/-0.10), (0.45+/-0.15) g/cm2; There were significantly decreased in BMD of hip at the age of 70-79, 80 89, >=90 year-old compared with those of 60-69 year-old (P<0.05). (2) Fracture incidence:one time fracture incidence at age of 60-69, 70-79, 80-89, >=90 were 34.8% (242/695), 45.0% (296/658), 51.3% (137/267), 5/17. There were increasing trend of fracture in aged women. (3) Bone turnover marker of bone Gla protein (BGP) N-mid (N-midBGP) in serum and C-terminal telopeptide of type I collagen/Cr (CTX/Cr) in urine values were (17+/-5) ug/L, (106+/-56) ug/mmol at age of more than 90 years, (17+/-7) ug/L, (128+/-99) ug/mmol at age of 80-89 years, (21+/-14) ug/L, (182+/-173) ug/mmol at age of 70-79 years, (25+/-13) ug/L, (190+/-168) ug/mmol at age of 60-69 years. There were significant decreased trends of N midBGP at age of 70-79, 80-89 compared with that of 60-year (P<0.05). There were significant decreased trends of CTX/Cr 80-89 compared with that of 60-year (P<0.05). CONCLUSIONS: There were significant decreased bone metabolism in aged women. The risk of hip fracture is significantly increased in aged women. Diagnosis of osteoporosis based on BMD of hip in aged women is more reliable. PMID- 22041440 TI - [Study on the relationship between vaginal and intestinal candida in patients with vulvovaginal candidiasis]. AB - OBJECTIVE: To investigate the relationship between vaginal and intestinal candida in patients with vulvovaginal candidiasis by using microbiological and molecular methods. METHODS: The samples of vaginal discharge and anal swabs were collected from 148 cases with vulvovaginal candidiasis, followed by fungal culture, identification, purification and genome DNA extraction. The genome sequences from respective locations were aligned and typed according to their homology analyzed by internal transcribed spacer (ITS) PCR and random amplified polymorphic DNA (RAPD) PCR. Patients with vulvovaginal infection or those with infections in intestine and vulvovagina were pooled respectively, while the recurrent incidences after local anti-fungal treatments were analyzed. RESULTS: Candida albicans is the dominant pathogen in 148 cases with vulvovaginal candidiasis (91.9%, 136/148); 33.1% (49/148) of patients with vulvovaginal candidiasis were infected in both intestine and vulvovagina. While 92% (22/24) of patients with intestinal and vaginal candida infection showed high homology. The recurrent rate of patients with vulvovaginal candidiasis complicated with concurrent intestinal candida infection (7/14) was significantly higher than that of solo vaginal infected patients [21% (6/29)] after vaginal treatment (P<0.05). CONCLUSIONS: The infection of vulvovaginal candidiasis is highly associated with the concurrent infection of intestinal candida. The recurrent rate is high in patients with vulvovaginal candidiasis with concurrent infection of intestinal candida after vaginal treatment. The general management to those patients infected by both vulvovaginal and intestinal candida is necessary in reducing the recurrence of the disease. PMID- 22041441 TI - [Study of quantitative detection of circulating DNA in the plasma of patients with cervical lesion]. AB - OBJECTIVE: To quantitatively detect circulating DNA levels in the plasma of patients withcervical lesion and to determine the value for diagnosis of cervical lesion and cervical cancer. METHODS: Preoperative blood samples were collected from 53 cases of low-grade lesions, 49 cases of high-grade lesions, 44 cases of cervical invasive cancer and 70 cases of healthy women. Plasma DNA was extracted by magnetic bead method (BILATEST DNA kit). The quantity of plasma DNA was determined by duplex real-time quantitative PCR. RESULTS: Median plasma DNA level of invasive cervical cancer patients was 61.59 mg/L (32.06-162.16 mg/L), which was significantly higher than that of healthy women [16.35 mg/L (11.98-22.71 mg/L), P<0.01]. Among invasive cervical cancer patients, median plasma DNA level of squamous carcinoma patients was slightly higher than that of adenocarcinoma (50.43 versus 47.31 mg/L, P>0.05). Median plasma DNA level of stage I patients was lower than that of stage II-III patients (46.02 versus 71.35 mg/L, P<0.05). CONCLUSION: Quantitatively detecting plasma circulating DNA may be with some application prospect in the diagnosis of cervical diseases. PMID- 22041442 TI - [Validation of incontinence impact questionnaire short form in Chinese population]. AB - OBJECTIVE: To study reliability and validity of incontinence impact questionnaire short form (IIQ-7) in the Chinese population. METHODS: IIQ-7 form was translated into Chinese; 74 patients with urinary incontinence completed the IIQ-7 simplified Chinese version and short-form 12-item health survey (SF-12) questionnaires. The urinary incontinence patient also ran a 1 hour pad test. Then, reliability and validity of those forms were analyzed. RESULTS: The Cronbach's alpha of IIQ-7 simplified Chinese version was 0.824 (P<0.01). The intra-class correlation coefficient of IIQ-7 simplified Chinese version was 0.749 (P<0.01). IIQ-7 simplified Chinese version scores were negatively correlated with SF-12 scores (Spearman correlation coefficient: -0.570, P<0.01), IIQ-7 simplified Chinese version scores were positively correlated with 1 hour pad test (Spearman correlation coefficient: 0.461, P<0.01), IIQ-7 simplified Chinese version scores were also positively correlated with the course of disease (Spearman correlation coefficient: 0.235, P<0.05). Factor analysis of IIQ-7 simplified Chinese version showed good construct validity. CONCLUSIONS: The simplified Chinese version of IIQ-7 has higher reliability and validity in the Chinese population. They are highly recommended for clinical treatment and research. PMID- 22041443 TI - [Expression and significance of LMP2 and PPM1A in gestational trophoblastic disease]. AB - OBJECTIVE: To investigate the expression of low molecular mass polypeptide-2 (LMP2) and protein phosphatase 1A (PPM1A) in gestational trophoblastic disease and elucidate their predictive value in malignant transformation of hydatidiform mole. METHODS: The expressions of LMP2 and PPM1A protein in 196 complete hydatidiform moles (in which 28 cases with malignant transformation), 7 invasive moles, 5 choriocarcinomas and 20 normal chorionic villus were detected with the method of EnVision immunohistochemistry. Their clinicopathologic data were retrospectively analyzed. RESULTS: LMP2 and PPM1A protein expressed in cytotrophocytes, syncytiotrophoblast and extravillous trophoblast. The level of LMP2 expression in deteriorative hydatidiform mole was significantly higher than that in non-deteriorative hydatidiform mole or normal chorionic villus (6.79+/ 2.38, 5.26+/-2.63 and 3.10+/-1.65, all P<0.01), while there were no difference compared with gestational trophoblastic neoplasms (6.42+/-2.68, P=0.113). The level of PPM1A expression was highest in normal chorionic villus, and decreased gradually in hydatidiform mole (non-deteriorative and deteriorative) and gestational trophoblastic neoplasms (6.30+/-2.98, 4.93+/-2.50, 4.43+/-2.04 and 3.33+/-2.06, all P<0.01); the level of PPM1A expression in deteriorative hydatidiform mole was significantly lower than that in non-deteriorative hydatidiform mole (P=0.001). The expression of LMP2 protein was correlated to theca lutein ovarian cyst, the expression of PPM1A protein was related with uterine size (P<0.05). While, there was no correlation between the expressions of the two proteins (P>0.05). CONCLUSIONS: High expression of LMP2 and low expression of PPM1A might play an important role in the motility and invasiveness of trophoblast cells and malignant transformation of hydatidiform mole. Testing the expression of LMP2 and PPM1A in hydatidiform mole tissues of initial uterine evacuation might be have some reference significance in judging outcomes of hydatidiform mole. PMID- 22041444 TI - [Application of pathological diagnosis by rapid paraffin sections for biopsy in the diagnosis and treatment of cervical diseases]. AB - OBJECTIVE: To evaluate the application of pathological diagnosis by rapid paraffin sections in the diagnosis and treatment of cervical diseases. METHODS: A total of 176 cases from our hospital between September 2009 and January 2010 with abnormal cervical cancer screening (including abnormal cytology result and high risk HPV continuous positive) were randomly divided into 2 groups. Eighty-seven cases of them whose biopsy were got by Belinson forceps under the direction of colposcopy with rapid paraffin sections by ultrasonic histopathological rapid processor and BT transparent agents were selected as group A, while 89 cases with conventional paraffin sections were selected as group B. The production time and quality for paraffin sections were analyzed in the two groups. Those diagnosed as cervical intraepithelial neoplasia (CIN) II or even worse and some special patients with CINI in the two groups received surgery, including loop electrosurgical procedure (LEEP), cold knife conization (CKC), hysterectomy or radical hysterectomy. Tissue obtained after surgery was sent for routine pathological examination. If the results of postoperative routine pathological examination were inconsistent with the rapid or routine biopsy pathological examination, the heavier results were regard as the final diagnoses. The pathological results and diagnose accordance rates were recorded and compared between group A and group B. RESULTS: The quality of sections in two groups were all satisfied or basically satisfied to meet the diagnostic requirements. There were statistically significant difference in average production time between group A and B (40 minutes vs 24 hours, P<0.05). Thirty patients in group A and 32 patients in group B received surgery. The coincidence rate of biopsy pathological results and final diagnoses were 93% (28/30) for group A and 91% (29/32) for group B, in which there were not statistically significant difference (P>0.05). CONCLUSION: Rapid paraffin sections technology is safe, accurate and economical for rapid pathological diagnosis of cervical diseases, which is worthy for being widely used in hospitals. PMID- 22041445 TI - [Effect of epidermal growth factor on the expression of matrix metalloproteinase 9 and the signalling pathways involved in the trophoblast cell line JEG-3]. AB - OBJECTIVE: To investigate the effect of epidermal growth factor (EGF) on the expression of Matrix metalloproteinase-9 (MMP-9) and the signalling pathways involved in the trophoblast cell line JEG-3. METHODS: The JEG-3 trophoblast cell line was used in this study. (1) JEG-3 cells were cultured with various concentrations of EGF (0, 1, 10, 20 ng/ml) for 24 hours and the expression of MMP 9 was tested by western blotting and reverse transcription PCR (RT-PCR). (2) Western blotting and RT-PCR were also used to investigate the expression of MMP-9 expression after incubation for 0, 4, 12 and 24 hours with EGF treatment (10 ng/ml) in JEG-3 cells. (3) According to the different added ingredients, JEG-3 cells were divided into some groups: control group (without EGF), EGF group (exposure to 10 ng/ml EGF), EGF+ inhibitors group (exposure to 10 ng/ml EGF+ 20 ng/ml SB203580 or exposure to 10 ng/ml EGF+ 10 ng/ml U0126), inhibitors group (exposure to 20 ng/ml SB203580 or exposure to 10 ng/ml U0126). Western blotting were used to investigate the expression levels of MMP-9, nuclear factor kappa B (NF-kappaB), p38MAPK, phospho-p38MAPK (p-p38MAPK), extracellular-signal regulated kinase (ERK) and phospho-ERK (p-ERK) protein in JEG-3 cells after incubation for 24 hours. RESULTS: (1) The profiles of MMP-9 mRNA were increased by various concentrations of EGF (0, 1, 10, 20 ng/ml) in JEG-3 cells after 24 h-culture. The expression of MMP-9 mRNA in JEG-3 cells exposure at 1 ng/ml of EGF (0.567+/ 0.056), 10 ng/ml of EGF (1.392+/-0.133), 20 ng/ml of EGF (1.971+/-0.067) were significantly higher respectively (P<0.05), compared with 0 ng/ml of EGF treatment (0.166+/-0.015). Similarly, MMP-9 mRNAs were also increased with the increasing incubation time. Compared to EGF (10 ng/ml) stimulation for 0 h (0.253+/-0.044), the MMP-9 mRNA profiles were 0.470+/-0.026, 1.061+/-0.115, 1.453+/-0.180 for 4, 12 and 24 hours, respectively (P<0.05). (2) In accordance to the mRNA profiles, the expression of MMP-9 protein was also increased by different concentrations of EGF (0, 1, 10, 20 ng/ml) in JEG-3 cells after 24 h culture. The abundance of MMP-9 protein in the three groups was 0.043+/-0.012, 0.085+/-0.008, 0.142+/-0.015, with a significantly higher expression, compared with 0 ng/ml of EGF treatment (0.004+/-0.001, P<0.05) respectively. Similarly, MMP-9 proteins were also increased with the increasing incubation time. Compared to EGF (10 ng/ml) stimulation for 0 h (0.030+/-0.009), the profiles of MMP-9 protein were 0.137+/-0.010, 0.240+/-0.010, 1.240+/-0.061 for 4, 12 and 24 hours, respectively (P<0.05). (3) Both p38MAPK and ERK signalling pathways were activated by EGF in JEG-3 cells. The expression of p-p38MAPK was significantly higher (without or with 10 ng/ml EGF, 234.1+/-4.1 vs. 260.9+/-2.5, P<0.05), however, the p38MAPK inhibitor SB203580 markedly suppressed the increase in p p38MAPK content induced by EGF (227.9+/-2.4 vs. 260.9+/-2.5, P<0.05). Similarly, the expression of p-ERK was significantly higher with EGF treatment (812.2+/-3.5) vs. without EGF group (453.4+/-5.8) (P<0.05), while the ERK inhibitor U0126 significantly inhibited the increased p-ERK content in response to EGF treatment (71.0+/-1.2 vs. 812.2+/-3.5, P<0.05). (4) The p38MAPK inhibitor SB203580 significantly reduced the expression of EGF-induced MMP-9 (0.645+/-0.270 vs. 1.476+/-0.452, P<0.05) and NF-kappaB (0.530+/-0.026 vs. 0.959+/-0.017, P<0.05). (5) The ERK inhibitor U0126 also significantly reduced the expression of EGF induced MMP-9 (0.623+/-0.030 vs. 2.112+/-0.056, P<0.05) and NF-kappaB (0.325+/ 0.082 vs. 0.939+/-0.153, P<0.05). CONCLUSION: EGF induced the expression of MMP-9 in a time and dose-dependant manner in JEG-3 cells. EGF enhanced MMP-9 expression through the activation of p38MAPK and ERK signalling pathways in JEG-3 cells. PMID- 22041446 TI - [Study on oriented differentiation of bone marrow mesenchymal stem cells by fibroblast in rat uterine ligament with mechanical stretch]. AB - OBJECTIVE: To investigate the effect on the differentiation of bone marrow mesenchymal stem cells (BMSC) with non-contact co-culture with mechanical stimulated ligament fibroblasts. METHODS: A cyclic 10% uniaxia strain at 1 Hz was applied on rat pelvic ligament fibroblasts, then were co-cultured with BMSC for 3, 6 and 12 days in non-contact condition. The protein expression of collagen I, III in BMSC were detected by SP method and revealed by the mean gray value. The mRNA expressions of collagens type I and type III in the BMSCs were measured with real-time (RT)-PCR, and the results were indicated by the ratio between the mRNA and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). RESULTS: (1) Protein expression: after 3 days co-culture with pelvic ligament fibroblasts, expression of collagen I and III in BMSC are 82.4+/-3.4 and 76.8+/-2.5. When compared with 80.2+/-2.6 and 74.6+/-1.1 in BMSC without co-culture, there was no significant difference (P>0.05). After 6 days co-culture with pelvic ligament fibroblasts, the expression of collagen I and III of 126.6+/-2.2 and 118.6+/-1.4 in BMSC were significantly higher than 82.7+/-3.0 and 76.2+/-1.3 in BMSC without co-culture (P<0.05). Similarly, after 12 days co-culture with pelvic ligament fibroblasts, the expression of collagen I and III of 135.3+/-3.4 and 128.7+/-2.6 in BMSC were significantly higher than 86.6+/-1.3 and 81.8+/-1.4 in BMSC without co-culture (P<0.05). (2) mRNA expression: after 3 days co-culture with pelvic ligament fibroblasts, the mRNA expression of type I and type III collagens in BMSC are 2.10+/-0.20 and 1.20+/-0.30. When compared with mRNA expression of 2.01+/-0.12 and 1.13+/-0.21 in BMSC without co-culture, no significant difference were observed (P>0.05). After 6 days co-culture with pelvic ligament fibroblasts, the mRNA expressions of type I and type III collagens mRNA were 5.60+/-0.21 and 2.61+/-0.20, which were significantly higher than 3.70+/-0.33 and 1.82+/-0.14 in BMSC without coculture (P<0.05). After 12 days co-culture with pelvic ligament fibroblasts, the mRNA expressions of type I and type III collagens of 5.91+/-0.31 and 2.92+/-0.23 were significantly higher than 4.04+/-0.21 and 2.04+/-0.13 in BMSC without co-culture (P<0.05). CONCLUSION: Non-contact co-culture with mechanical stretch stimulated ligament fibroblasts, it might promote synthesis of types Iand III collagen in rat BMSCs and induced BMSC differentiated into pelvic ligament fibroblasts. PMID- 22041447 TI - [Establishment of cisplatin-resistant human endometrial cancer cell line and the study of its resistant mechanisms]. AB - OBJECTIVE: To establish the cisplatin (DDP)-resistant cell line from human endometrial cancer cell line Ishikawa and to investigate its resistant mechanism to DDP. METHODS: A resistant endometrial cancer cell line ISH/DDP was established by gradually increasing dose of cisplatin and high-dose stimulation. The resistant index was estimated by 3-(4,5-dimethylthiazol-zyl)-5-(3 carboxymethoxyphenyl-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Cell growth curve, doubling time and cell cycle phase distribution were measured; drug-resistant protein of breast cancer resistance protein (BCRP), P-glycoprotein (P-gp) and glutathione-S-transferase-pi (GST-pi) were examined by immuocytochemistry. Results The DDP-resistant cell line ISH/DDP was established with the resistant index of 3.77. The proliferation of ISH/DDP got slow, doubling time prolonged, which were 40.1 hours, while it was 34.1 hours in Ishikawa (P<0.05); and the cell number of G0/G1 phase [(44.3+/-5.7)% and (39.0+/-10.7)%, P>0.05] and G2/M phase [(11.9+/-0.7)% and (5.7+/-2.4)%, P<0.05] decreased, while S-phase [(44.2+/-6.1)% and (55.3+/-8.4)%, P<0.05] increased compared with parent cells. The comprehensive score of the expression of BCRP in ISH/DDP was 16.3+/ 2.0, while it was 13.4+/-1.5 in Ishikawa (P<0.05). The score of the expression of P-gp in ISH/DDP and Ishikawa were 15.5+/-1.2 and 16.1+/-1.0 (P>0.05), respectively. The score of the expression of GST-pi in ISH/DDP and Ishikawa were 15.2+/-1.9 and 14.9+/-1.1 (P>0.05). CONCLUSION: ISH/DDP cell line showed a typical resistant phenotype and biological characteristics, which may be accounted for high BCRP expression. PMID- 22041448 TI - Prevalence and characteristics of quinolone resistance in Escherichia coli in veal calves. AB - Quinolone resistance is studied and reported increasingly in isolates from humans, food-producing animals and companion animals. Resistance can be caused by chromosomal mutations in topoisomerase genes, plasmid-mediated resistance genes, and active transport through efflux pumps. Cross sectional data on quinolone resistance mechanisms in non-pathogenic bacteria from healthy veal calves is limited. The purpose of this study was to determine the prevalence and characteristics of quinolone resistance mechanisms in Escherichia coli isolates from veal calves, after more than 20 years of quinolone usage in veal calves. MIC values were determined for all isolates collected as part of a national surveillance program on antimicrobial resistance in commensal bacteria in food producing animals in The Netherlands. From the strains collected from veal calves in 2007 (n=175) all isolates with ciprofloxacin MIC >= 0.125 mg/L (n=25) were selected for this study, and screened for the presence of known quinolone resistance determinants. In this selection only chromosomal mutations in the topoisomerase type II and IV genes were detected. The number of mutations found per isolate correlated with an increasing ciprofloxacin MIC. No plasmid-mediated quinolone resistance genes were found. The contribution of efflux pumps varied from no contribution to a 16-fold increase in susceptibility. No correlation was found with the presence of resistance genes of other antimicrobial classes, even though all quinolone non-wild type isolates were resistant to 3 or more classes of antibiotics other than quinolones. Over twenty years of quinolone usage in veal calves in The Netherlands did not result in a widespread occurrence of plasmid-mediated quinolone resistance, limiting the transmission of quinolone resistance to clonal distribution. PMID- 22041450 TI - Human cardiac myosin binding protein C: structural flexibility within an extended modular architecture. AB - New insights into the modular organization and flexibility of the N-terminal half of human cardiac myosin binding protein C (cMyBP-C) and information on the association state of the full-length protein have been deduced from a combined small-angle X-ray scattering (SAXS) and NMR study. SAXS data show that the first five immunoglobulin domains of cMyBP-C, which include those implicated in interactions with both myosin and actin, remain monodisperse and monomeric in solution and have a highly extended yet distinctively 'bent' modular arrangement that is similar to the giant elastic muscle protein titin. Analyses of the NMR and SAXS data indicate that a proline/alanine-rich linker connecting the cardiac specific N-terminal C0 domain to the C1 domain provides significant structural flexibility at the N-terminus of the human isoform, while the modular arrangement of domains C1-C2-C3-C4 is relatively fixed. Domain fragments from the C-terminal half of the protein have a propensity to self-associate in vitro, while full length bacterially expressed cMyBP-C forms flexible extended dimers at micromolar protein concentrations. In summary, our studies reveal that human cMyBP-C combines a distinctive modular architecture with regions of flexibility and that the N-terminal half of the protein is sufficiently extended to span the range of interfilament distances sampled within the dynamic environment of heart muscle. These structural features of cMyBP-C could facilitate its putative role as a molecular switch between actin and myosin and may contribute to modulating the transverse pliancy of the C-zone of the A-band across muscle sarcomeres. PMID- 22041449 TI - Crystal structure of the ligand binding domain of netrin G2. AB - Netrin G proteins represent a small family of synaptic cell adhesion molecules related to netrins and to the polymerization domains of laminins. Two netrin G proteins are encoded in vertebrate genomes, netrins G1 and G2, which are known to bind the leucine-rich repeat proteins netrin G ligand (NGL)-1 and NGL-2, respectively. Netrin G proteins share a common multi-domain architecture comprising a laminin N-terminal (LN) domain followed by three laminin epidermal growth factor-like (LE) domains and a C' region containing a glycosylphosphatidylinositol anchor. Here, we use deletion analysis to show that the LN domain region of netrin Gs contains the binding site for NGLs to which they bind with 1:1 stoichiometry and sub-micromolar affinity. Netrin Gs are alternatively spliced in their LE domain regions, but the binding region, the LN domain, is identical in all splice forms. We determined the crystal structure for a fragment comprising the LN domain and domain LE1 of netrin G2 by sulfur single wavelength anomalous diffraction phasing and refined it to 1.8 A resolution. The structure reveals an overall architecture similar to that of laminin alpha chain LN domains but includes significant differences including a Ca(2+) binding site in the LN domain. These results reveal the minimal binding unit for interaction of netrin Gs with NGLs, define structural features specific to netrin Gs, and suggest that netrin G alternative splicing is not involved in NGL recognition. PMID- 22041451 TI - The role of tropomyosin domains in cooperative activation of the actin-myosin interaction. AB - To establish alpha-tropomyosin (Tm)'s structure-function relationships in cooperative regulation of muscle contraction, thin filaments were reconstituted with a variety of Tm mutants (Delta2Tm, Delta3Tm, Delta6Tm, P2sTm, P3sTm, P2P3sTm, P1P5Tm, and wtTm), and force and sliding velocity of the thin filament were studied using an in vitro motility assay. In the case of deletion mutants, Delta indicates which of the quasi-equivalent repeats in Tm was deleted. In the case of period (P) mutants, an Ala cluster was introduced into the indicated period to strengthen the Tm-actin interaction. In P1P5Tm, the N-terminal half of period 5 was substituted with that of period 1 to test the quasi-equivalence of these two Tm periods. The reconstitution included bovine cardiac troponin. Deletion studies revealed that period 3 is important for the positive cooperative effect of Tm on actin filament regulation and that period 2 also contributes to this effect at low ionic strength, but to a lesser degree. Furthermore, Tm with one extra Ala cluster at period 2 (P2s) or period 3 (P3s) did not increase force or velocity, whereas Tm with two extra Ala clusters (P2P3s) increased both force and velocity, demonstrating interaction between these periods. Most mutants did not move in the absence of Ca(2+). Notable exceptions were Delta6Tm and P1P5Tm, which moved near at the full velocity, but with reduced force, which indicate impaired relaxation. These results are consistent with the mechanism that the Tm actin interaction cooperatively affects actin to result in generation of greater force and velocity. PMID- 22041452 TI - A repeated coiled-coil interruption in the Escherichia coli condensin MukB. AB - MukB, a divergent structural maintenance of chromosomes (SMC) protein, is important for chromosome segregation and condensation in Escherichia coli and other gamma-proteobacteria. MukB and canonical SMC proteins share a common five domain structure in which globular N- and C-terminal regions combine to form an ATP-binding-cassette-like ATPase domain. This ATPase domain is connected to a central, globular dimerization domain by a long antiparallel coiled coil. The structures of both globular domains have been solved recently. In contrast, little is known about the coiled coil, in spite of its clear importance for SMC function. Recently, we identified interacting regions on the N- and C-terminal halves of the MukB coiled coil through photoaffinity cross-linking experiments. On the basis of these low-resolution experimental constraints, phylogenetic data, and coiled-coil prediction analysis, we proposed a preliminary model in which the MukB coiled coil is divided into multiple segments. Here, we use a disulfide cross-linking assay to detect paired residues on opposite strands of MukB's coiled coil. This method provides accurate register data and demonstrates the presence of at least five coiled-coil segments in this domain. Moreover, these studies show that the segments are interrupted by a repeated, unprecedented deviation from canonical coiled-coil structure. These experiments provide a sufficiently detailed view of the MukB coiled coil to allow rational manipulation of this region for the first time, opening the door for structure-function studies of this domain. PMID- 22041453 TI - Stopping the control arm in response to the DSMB: mother's choice of HIV prophylaxis during breastfeeding in the BAN Study. AB - The Data and Safety Monitoring Board (DSMB) for the Breastfeeding, Antiretrovirals, and Nutrition study, a clinical trial aimed to prevent postnatal HIV transmission, recommended halting randomization to the enhanced standard-of care (control) arm. The 67 mother-infant pairs on the control arm and less than 21 weeks postpartum at the time of the DSMB recommendation were read a script informing them of the DSMB decision and offering them the maternal or infant antiretroviral interventions for the remainder of the 28-week breastfeeding period. This paper describes the BAN study response to the DSMB decision and what the women on the control arm chose, when given a choice to start the maternal or infant antiretroviral interventions. PMID- 22041454 TI - Oxidants, metabolism, and stem cell biology. AB - Adult stem cells persist throughout the lifetime of the organism and may therefore require specific mechanisms to limit the effects of chronic oxidative stress. Recently, several instructive genetic mouse models have demonstrated the unique susceptibility of stem cells to perturbations in metabolic or redox homeostasis. These results have implications not only for stem cell biology but also suggest a mechanistic link between intracellular oxidants and the decline in regenerative function that occurs as a normal consequence of aging. PMID- 22041455 TI - Monascin from red mold dioscorea as a novel antidiabetic and antioxidative stress agent in rats and Caenorhabditis elegans. AB - Monascin is a major yellow compound from red mold dioscorea. We investigated monascin to test whether this compound acts as an antidiabetic and antioxidative stress agent in diabetic rats and Caenorhabditis elegans. The mechanisms by which monascin exerts its action in vivo were also examined. Streptozotocin (STZ) induced diabetic rats were given monascin at 30 mg/kg/day and sacrificed after 8 weeks. Blood glucose and serum insulin, triglyceride, total cholesterol, and high density lipoprotein and antioxidative enzymes in the pancreas of rats were measured. In addition, monascin was evaluated for stress resistance and potential associated mechanisms in C. elegans. Throughout the 8-week experimental period, significantly lowered blood glucose, serum triglyceride, and total cholesterol and higher high-density lipoprotein levels were observed in monascin-treated rats. Monascin-treated rats showed higher serum insulin level, lower reactive oxygen species production, and higher activities of glutathione peroxidase, superoxide dismutase, and catalase in the pancreas compared to diabetic control rats. In addition, monascin significantly induced the hepatic mRNA levels of FOXO3a, FOXO1, MnSOD, and catalase in STZ-induced diabetic rats. Monascin-treated C. elegans showed an increased survival rate during oxidative stress and heat stress treatments compared to untreated controls. Moreover, monascin extended the life span under high-glucose conditions and enhanced expression of small heat shock protein (sHSP-16.2), superoxide dismutase (SOD-3), and glutathione S transferase (GST-4) in C. elegans. Finally, we showed that monascin affected the subcellular distribution of the FOXO transcription factor DAF-16, whereas it was unable to enhance oxidative stress resistance in the daf-16 deletion mutant in C. elegans. Mechanistic studies in rats and C. elegans suggest that the protective effects of monascin are mediated via regulation of the FOXO/DAF-16-dependent insulin signaling pathway by inducing the expression of stress response/antioxidant genes, thereby enhancing oxidative stress resistance. PMID- 22041456 TI - Genomic instability induced by mutant succinate dehydrogenase subunit D (SDHD) is mediated by O2(-*) and H2O2. AB - SDHD mutations are associated with human cancers but the mechanisms that may contribute to transformation are unknown. The hypothesis that mutations in SDHD increase levels of superoxide leading to genomic instability was tested using site-directed mutagenesis to generate a truncated SDHD cDNA that was expressed in Chinese hamster fibroblasts. Stable expression of mutant SDHD resulted in 2-fold increases in steady-state levels of superoxide that were accompanied by a significantly increased mutation rate as well as a 70-fold increase in mutation frequency at the hprt locus. Overexpression of MnSOD or treatment with polyethylene glycol conjugated (PEG)-catalase suppressed mutation frequency in SDHD mutant cells by 50% (P<0.05). Simultaneous treatment with PEG-catalase and PEG-SOD suppressed mutation frequency in SDHD mutant cells by 90% (P<0.0005). Finally, 95% depletion of glutathione using l-buthionine-[S,R]-sulfoximine (BSO) in SDHD mutant cells caused a 4-fold increase in mutation frequency (P<0.05). These results demonstrate that mutations in SDHD cause increased steady-state levels of superoxide which significantly contributed to increases in mutation rates and frequency mediated by superoxide and hydrogen peroxide. These results support the hypothesis that mutations in SDHD may contribute to carcinogenesis by increasing genomic instability mediated by increased steady-state levels of reactive oxygen species. PMID- 22041457 TI - Wnt/beta-catenin pathway forms a negative feedback loop during TGF-beta1 induced human normal skin fibroblast-to-myofibroblast transition. AB - BACKGROUND: Fibroblast-to-myofibroblast transition is a key event during wound healing and hypertrophic scar formation. Previous studies suggested Wnt/beta catenin signaling might be involved in the wound healing. However, its specific role in skin fibroblast-to-myofibroblast transition remains unclear. OBJECTIVE: To investigate the specific role of beta-catenin during the transforming growth factor-beta1 induced normal skin myofibroblasts transition. METHODS: By real-time quantitative polymerase chain reaction, Western-blot and immunocytochemistry, the activation of Wnt/beta-catenin pathway in cultured human normal skin fibroblasts during TGF-beta1 induced fibroblast-to-myofibroblast transition was investigated. The effects of beta-catenin on myofibroblasts transition were also investigated when SB-216763, over-expression and siRNA of beta-catenin were utilized. In addition, fibroblasts populated collagen lattices contraction assays were conducted to examine the effects of beta-catenin on the contractility of the fibroblasts induced by TGF-beta1. Furthermore, the effects of beta-catenin on the expression of alpha-smooth muscle actin and collagen types I and III in hypertrophic scar derived fibroblasts were studied. RESULTS: The expression of Wnts mRNA and beta-catenin protein was up-regulated by TGF-beta1 stimulation during the myofibroblasts transition. Both of SB-216763 and beta-catenin over expression was paralleled with decreased expression of alpha-smooth muscle actin, collagen types I and III, while siRNA targeting beta-catenin leads to up regulation of alpha-smooth muscle actin, collagen types I and III. The increased contractility and alpha-smooth muscle actin expression of the fibroblasts in the collagen lattices induced by TGF-beta1 was inhibited by SB-216763. In addition, the expression levels of alpha-smooth muscle actin, collagen types I and III in hypertrophic scar derived fibroblasts were also down-regulated by SB-216763. CONCLUSION: Specifically in normal skin fibroblasts, beta-catenin might be involved in the myofibroblasts transition and negatively regulate the TGF-beta1 induced myofibroblast transition. PMID- 22041458 TI - Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D. AB - BACKGROUND: Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression. METHOD: We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries. RESULTS: Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p = 4.98 * 10(-7), q = 0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1. CONCLUSIONS: Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication. PMID- 22041459 TI - DNA methylation in stem cell renewal and multipotency. AB - Owing to their potential for differentiation into multiple cell types, multipotent stem cells extracted from many adult tissues are an attractive stem cell resource for the replacement of damaged tissues in regenerative medicine. The requirements for cellular differentiation of an adult stem cell are a loss of proliferation potential and a gain of cell-type identity. These processes could be restricted by epigenetic modifications that prevent the risks of lineage unrelated gene expression or the undifferentiated features of stem cells in adult somatic cells. In this review, we focus on the role of DNA methylation in controlling the transcriptional activity of genes important for self-renewal, the dynamism of CpG methylation of tissue-specific genes during several differentiation programs, and whether the multilineage potential of adult stem cells could be imposed early in the original precursor stem cells through CpG methylation. Additionally, we draw attention to the role of DNA methylation in adult stem cell differentiation by reviewing the reports on spontaneous differentiation after treatment with demethylating agents and by considering the evidence provided by reprogramming of somatic cells into undifferentiated cells (that is, somatic nuclear transfer or generation of induced pluripotent cells). It is clear from the evidence that DNA methylation is necessary for controlling stem cell proliferation and differentiation, but their exact contribution in each lineage program is still unclear. As a consequence, in a clinical setting, caution should be exerted before employing adult stem cells or their derivatives in regenerative medicine and appropriate tests should be applied to ensure the integrity of the genome and epigenome. PMID- 22041460 TI - Stereoselective synthesis of (RP)-8-substituted-N6-acylated and N6-alkylated adenosine-3',5'-cyclic phosphorothioic acids as cAMP antagonists. AB - N(6)-Monoalkylated, N(6)-dialkylated and N(6)-acylated (R(P))-adenosine 3',5' cyclic phosphorothioic acids have been prepared by stereoselective syntheses from cAMP for a study of protein kinase A antagonist activity. The antagonist activity of the parent primary 6-amino cAMP derivative was reduced after N-monoalkylation. No significant activity was detected in the N,N-dialkylated derivative. Mono N acylation had little effect on the activity. Hydrogen bonding involving the 6 amino group in cAMPS seems necessary for activity. PMID- 22041461 TI - Randomised trials in child health in developing countries 2011. PMID- 22041462 TI - Big hopes for the children of the world: a review of the Millennium Development Goals. AB - The Millennium Development Goals are a set of eight goals drafted by the United Nations in 2000 with the aim of improving the health and welfare of people worldwide. The goals provide specific targets to be met by 2015, using the 1990 basis as a standard. This review presents these goals as they relate to children, discussing progress and future aims. Although not all eight goals specifically address children, each has its own impact on global child health. Thus far, much progress has been made, but increased rates of improvement must be achieved in order to meet the goals by 2015 and improve the health of children worldwide. PMID- 22041463 TI - Missed opportunities for prevention of tuberculosis in children. PMID- 22041464 TI - Opportunities for chemoprophylaxis in children with culture-confirmed tuberculosis. AB - BACKGROUND AND OBJECTIVES: Chemoprophylaxis is an effective strategy to prevent progression of tuberculosis (TB) in vulnerable children who have had contact with an infectious source of TB. However, many operational gaps prevent implementation of routine chemoprophylaxis in high-burden settings. The TB exposure status and disease spectrum in children diagnosed with culture-confirmed TB are described and missed opportunities for chemoprophylaxis are highlighted. METHODS: All children <13 years of age diagnosed with culture-confirmed TB at a tertiary referral hospital between March 2003 and February 2007 were included. Clinical data were collected from retrospective review of files. TB was classified as pulmonary and extra-pulmonary; disseminated TB included miliary disease and TB meningitis. RESULTS: During the study period, 614 children (327, 53.3% boys, median age 32 months) were diagnosed with culture-confirmed TB. Contact with an infectious adult source case was documented in 333 (54.2%), 237 (71.2%) of whom were <5 years of age, and 24 (7.2%) were HIV-infected and >=5 years of age. Of those eligible for chemoprophylaxis, missed opportunities were identified in 156/221 (70.6%) children; 127 (81.4%) were <3 years of age, 39 (25%) had disseminated TB and 8 (5.1%) died. The TB source case was the mother or father in 74/156 (47.4%) children. CONCLUSION: Opportunities for initiation of chemoprophylaxis in vulnerable children following TB exposure are often missed. Awareness should be increased among health-care workers and in the community at large regarding the importance of chemoprophylaxis in young and HIV-infected children. Health system strengthening is required to improve delivery of chemoprophylaxis to vulnerable children in close contact with newly diagnosed infectious TB cases. PMID- 22041465 TI - Co-morbidity: exploring the clinical overlap between pneumonia and diarrhoea in a hospital in Dhaka, Bangladesh. AB - BACKGROUND: There is limited information on risk factors for pneumonia and pneumonia-related deaths in children who also have diarrhoea. AIM: To identify risk factors for the above in order to improve strategies for case management and to develop appropriate public health messages. METHODS: All children under 5 years of age admitted to the Special Care Ward, Dhaka Hospital of the International Centre for Diarrhoeal Disease Research (ICDDR,B) from 1 September to 31 December 2007 were considered for enrollment if they also had diarrhoea. Of the 258 children with diarrhoea enrolled, those with (n=198) or without (n=60) WHO-defined pneumonia constituted the pneumonia and comparison groups, respectively. Among the 198 children with pneumonia, children who survived (n=174) were compared with those who died in hospital (n=24). RESULTS: After adjusting for socio-demographic factors, including low levels of literacy of either parent, low household income, not having a window or exhaust fan in the kitchen, household smoking and over-crowding, children with pneumonia were more likely to sleep on a bare wooden-slatted or bamboo bed (OR 2.7, 95% CI 1.40-5.21, p = 0.003) than on other bedding, and were also more likely to have a parent/care giver with poor knowledge of pneumonia (OR 1.94, 95% CI 1.02-3.70, p=0.043). Independent risk factors for death include severe underweight (OR 5.2, 95% CI 1.2 22.0, p=0.03), hypoxaemia (OR 17.5, 95% CI I 1.9-160.0, p=0.01), severe sepsis (OR 8.7, 95% CI I 1.8-41.5, p=0.007) and lobar consolidation (OR 11.9, 95% CI 2.3 61.6, p=0.003). CONCLUSIONS: Increased public awareness of signs of pneumonia and severe sepsis in children under 5 is important to mitigate the risks of pneumonia and pneumonia-related deaths, and the importance of appropriate bedding for young children in reducing the risk of pneumonia needs to be addressed. PMID- 22041466 TI - Relationship of household food insecurity to anaemia in children aged 6-59 months among families in rural Indonesia. AB - BACKGROUND: Anaemia is a significant global public health problem in developing countries with adverse health effects on young children. Household food insecurity, which reflects a household's access, availability and utilisation of food, has not been well characterised in relation to anaemia in children. OBJECTIVE: To examine the relationship of household food insecurity with anaemia (Hb <11 g/dl) in children. METHODS: In a cross-sectional study of 4940 rural households participating in the Indonesian Nutrition Surveillance System, household food insecurity was measured using a modified 9-item food security questionnaire and related to anaemia in children aged 6-59 months. RESULTS: The proportion of households with an anaemic child was 56.6%. In households with and without anaemic children, the mean (SD) food insecurity score was 1.82 (1.72) vs 1.55 (1.54) (p<0.0001), respectively. In a multivariate logistic regression model, food insecurity score was related to anaemia in children (odds ratio 0.77, 95% confidence interval 0.63-0.95, p=0.01) when the highest quintile of food insecurity score was compared with the lowest quintile, adjusting for potential confounders. CONCLUSION: A higher household food insecurity score is associated with greater prevalence of anaemia in children in rural families in Indonesia. PMID- 22041467 TI - Adherence to antiretroviral therapy and its correlates among HIV-infected children at an HIV clinic in New Delhi. AB - BACKGROUND: With the introduction of antiretroviral therapy (ART), the mortality and morbidity of HIV/AIDS have decreased markedly. However, high adherence to ART (>95%) is necessary for a good therapeutic outcome. There is a paucity of data on paediatric adherence to ART and its correlates from developing countries, particularly India. AIM: To determine the rate of adherence to ART in HIV infected Indian children and the factors associated with adherence. METHODS: A cross-sectional study was conducted at an ART clinic in New Delhi, north India. Caregivers of 90 children were interviewed using a pre-designed, structured questionnaire and checklist. The primary measure of adherence was 4-day caregiver's recall. Adherence rates were correlated with 3-monthly CD4 counts. RESULTS: Mean (SD, range) adherence was 91.4% (12.3, 75-100%). Adherence was low (<95%) in 31 (34.4%) patients. On multivariate logistic regression analysis, increasing time since ART initiation (OR 1.08, 95% CI 1.02-1.13), low caregiver educational status (OR 4.19, 95% CI 1.37-10.88), orphanhood (OR 3.57, 95% CI 1.13-9.25), efavirenz-based ART regimens (OR 3.65, 95% CI 1.05-10.69) and female gender (OR 3.15, 95% CI 1.03-7.68) were associated with lower adherence. The rise in CD4 count after ART initiation was more marked in the high adherence group, with the difference in the two groups becoming statistically significant after 6 months of ART (median CD4 count 698 vs 355, p=0.016). CONCLUSIONS: It is possible to achieve high adherence to ART in a resource-limited setting. Caregiver recall is a reliable and inexpensive tool for measuring adherence. Paediatric adherence to ART is influenced by numerous factors and larger studies are needed to address the issue in India. PMID- 22041468 TI - Immediate versus as-needed acetaminophen for post-immunisation pyrexia. AB - BACKGROUND: Local and minor systemic adverse events are frequently seen after routine immunisation with diphtheria-pertussis-tetanus. Antipyretics are frequently prescribed for these events and prophylactic administration of acetaminophen is occasionally recommended. OBJECTIVE: To determine whether prophylactic administration of acetaminophen has any effect in reducing the incidence of post-vaccination side-effects. DESIGN: A prospective, comparative trial with telephone interview-based outcome assessment. SETTING: OPD and immunisation room of a tertiary-care paediatric hospital. SUBJECTS AND METHODS: 167 children aged between 1.5 and 24 months presenting for routine immunisation were enrolled and allocated to the 'immediate' or 'as-needed' group. The immediate group had received acetaminophen syrup (10-15 mg/kg, single dose) immediately after vaccination (n=89); children in the as-needed group were not given prophylactic acetaminophen (n=78). Parents of both groups were free to give further doses of acetaminophen for fever, pain or irritability. The primary outcome was the incidence of parent-reported fever needing rescue acetaminophen, and the secondary outcome was the incidence of local side-effects. RESULTS: There was a statistically significant higher incidence of fever and irritability in the 1st 6 hours following vaccination in the as-needed group (p=0.04). No difference was observed in the incidence of local and systemic side-effects or the median number of acetaminophen doses required by the children in the two groups. CONCLUSIONS: Routine prophylactic acetaminophen after DPT vaccination was effective in reducing the frequency of fever and irritability in the initial 6 hours. However, given that a similar number of doses of acetaminophen was required in both groups, it seems inappropriate to expose all infants receiving DPT vaccination to the possible adverse effects of routine administration of acetaminophen. PMID- 22041469 TI - Serum zinc levels are low in children with simple febrile seizures compared with those in children with epileptic seizures and controls. AB - AIM: To investigate serum zinc levels in children with simple febrile and epileptic seizures and compare them with controls. METHODS: A prospective, case control study was conducted between July 2009 and September 2010 in Kanchi Kamakoti CHILDS Trust Hospital, Chennai. Sixty-seven children (22 with epileptic seizures, 23 with simple febrile seizures and 22 controls) were enrolled. Serum zinc level was estimated using atomic absorption spectrometry. RESULTS: Mean (SD) serum zinc level in children with epileptic seizures, simple febrile seizures and controls were 969.8 (177.3), 638.1 (206.8) and 939.9 (258.4) ug/L, respectively (p<0.05). CONCLUSION: Serum zinc levels are lower in children with febrile seizures than in those with epileptic seizures and normal children. Zinc supplementation of children at risk of febrile seizures requires further study. PMID- 22041470 TI - Clinical profiles of 13 children with Plasmodium vivax cerebral malaria. AB - BACKGROUND: Bikaner region is endemic for both P. vivax and P. falciparum malaria. Usually, cerebral malaria is caused by P. falciparum but it has been reported recently also in P. vivax mono-infection. Epidemiologic studies and clinical descriptions of P. vivax cerebral malaria in children are rare. AIMS: To describe the clinical features of PCR-confirmed cerebral malaria owing to P. vivax mono-infection and its clinico-laboratory profile in Bikaner, Northwest India. METHODS: This observational prospective study was based on detailed clinical and laboratory investigation of children admitted with cerebral malaria owing to P. vivax between November 2008 and December 2010. Cerebral malaria was categorised according to the WHO (2000) criteria for P. falciparum and the diagnosis of P. vivax mono-infection was established by peripheral blood film and rapid diagnostic tests and confirmed by polymerase chain reaction. The possibility of other diseases/infections causing similar illness were investigated thoroughly. RESULTS: Thirteen children with P. vivax cerebral malaria were studied, eight of whom (61.5%) had multi-organ (two or more organs) dysfunction. Other associated severe manifestations included severe anaemia (7), hepatic dysfunction (2), renal dysfunction (2), bleeding manifestation (2), respiratory distress (2), metabolic acidosis (2) and shock (one). Hypoglycaemia was not observed in any patient. There was no evidence of neurological sequelae. All the children were managed according to WHO guidelines using intravenous artisunate. Thrombocytopenia was detected in five and hyponatraemia in four children. CONCLUSION: P. vivax mono-infection can cause cerebral malaria and multi-organ dysfunction. PMID- 22041471 TI - Pulmonary langerhans cell histiocytosis masquerading as tuberculosis in an infant. AB - A 4-month-old infant presented with continued fever, unresolving bronchopneumonia and household contact with sputum-smear-positive tuberculosis (TB) and showed marginal improvement on anti-TB chemotherapy. Recurrent pneumothorax prompted the clinical diagnosis of TB to be revised. High-resolution CT scan of the chest and open lung biopsy confirmed the diagnosis of pulmonary Langerhans cell histiocytosis. Treatment with prednisolone and vinblastin resulted in settling of fever and resolution of respiratory symptoms and signs. In communities where the prevalence of TB is high, unusual presentations should prompt consideration of alternative diagnoses. PMID- 22041472 TI - Bilateral symmetrical facial swelling owing to tuberculous gummas. AB - Metastatic tuberculous abscesses and gummas are unusual forms of cutaneous tuberculosis. They result from haematogeneous spread of the mycobacterium from a primary focus during a period of impaired immunity. A 5-year-old boy is reported who presented with spinal tuberculosis and bilateral subcutaneous swelling of the cheeks owing to tuberculous gummas. PMID- 22041473 TI - Primary tuberculous cerebellar abscess: case report. AB - Tuberculous cerebellar abscess is a rare manifestation of central nervous system tuberculosis. An 8-year-old boy is described who presented with acute hydrocephalus and right hemiparesis owing to a cerebellar abscess. PMID- 22041475 TI - Epilepsy surgery in children compared to adults. AB - AIM: The purpose of this study was to compare the frequency of various surgical techniques and surgical outcome between pediatric and adult populations that underwent epilepsy surgery by the same team. METHODS: All patients who underwent epilepsy surgery at the Tel Aviv Medical Center between 1997 and 2006 and had been followed up for >2 years were eligible for this study. The majority (90%) of all epilepsy surgeries carried out in Israel were performed in this institution and by a single neurosurgeon. Only patients that underwent video-EEG monitoring as part of the presurgical evaluation were included in the study. RESULTS: A total of 186 patients (131 adults and 55 children) underwent epilepsy surgery in our institute during the study period, and follow-up was available for 177 patients (95%). While the adults underwent significantly more temporal lobe resections (51 vs. 20%, p < 0.0001), the children had significantly more extra temporal non-lesional resections (18 vs. 1%, p < 0.0001) and hemispherectomies (5 vs. 1%, p = 0.002). Over one half (54%) of all the patients had a postoperative reduction in seizures of >90%, and 72% had a reduction of >50%, with no group difference in surgical success. Among the lesionectomies, the outcome was better for tumors, especially those in the temporal lobe. Only 1% of the patients had a long-term neurological deficit. CONCLUSIONS: Children comprised 30% of the epilepsy surgical cases during the study period. Children underwent more non lesional resections and hemispherectomies, while adults underwent more temporal lobe resections. There was no age-related difference in surgical outcome. PMID- 22041476 TI - Medullary decussation of the lateral corticospinal tract. PMID- 22041477 TI - The occurrence of Listeria monocytogenes in imported ready-to-eat foods in Japan. AB - Quantitative analyses of Listeria monocytogenes in imported ready-to-eat (RTE) foods sold at retail stores in Japan were performed. Of the 77 non-cooked meat products, 6 samples (7.8%) tested positive. The levels of contamination of 4 of the samples were below 100 colony-forming units (CFU)/g, which is the microbiological criterion for L. monocytogenes in RTE foods as determined by Codex. However, Listeria cells at levels of 100 and 400 CFU/g were detected in a salami sample and a raw ham sample, respectively. All of the 70 cheese samples and the 3 samples made from raw ham and cheese showed negative test results. These results suggest that imported RTE foods are potential sources of the causative agent of listeriosis. PMID- 22041479 TI - [Paying more attention on the effects of excimer laser corneal refractive surgeries on the corneal biomechanical integrality]. AB - Until now, in the territory of surgical methods, excimer laser refractive surgeries have being the main stream for correcting the ametropic eyes. The main cause of iatrogenic corneal ectasia and keratoconus, one of the most severe complications of corneal refractive surgeries, is the destruction of corneal biomechanics. Keeping corneal biomechanical integrality is the basis for long term effectiveness, stableness, and safety of the corneal refractive surgeries. The reasonable indication and surgical method decision, perioperative medical cares play very important roles in preventing those severe complications. PMID- 22041478 TI - Reduction of oxidative damage reflects a better kidney transplantation outcome. AB - BACKGROUND/AIMS: DNA fragmentation is one of the typical features of apoptosis, frequently induced by oxidative stress. Increased oxidative stress is known to be related to several pathological processes. In this study, we assessed oxidative damage in the early follow-up period after kidney transplantation measuring DNA oxidation and fragmentation of mononuclear cells and the circulating levels of inflammatory cytokines. METHODS: Blood samples from 30 kidney transplant recipients were collected before transplantation and after 2 days, 1 month and 6 months. Oxidative DNA fragmentation was measured by Comet Assay, whereas DNA oxidation was evaluated measuring 8-OHdG leukocyte levels. Serum IL-1beta, IL-4, IL-6, IL-8, IL-10, IFN-gamma and TNF-alpha were assayed using a multiplex ELISA analysis. RESULTS: At 6 months after transplantation, a significant reduction in DNA fragmentation and IL-6 plasma levels was observed; DNA oxidation was higher in patients with a worse outcome, with delayed graft function and low nutritional status. We also found a correlation of IL-6 and IL-10 levels with DNA fragmentation and of IL-10 levels with DNA oxidation. CONCLUSION: Low levels of oxidation and apoptosis at 6 months after transplantation correlate with a better recovery of renal function in kidney allografts. The measurement of cytokine levels confirmed a reduction of inflammatory parameters within 6 months of follow up. PMID- 22041480 TI - [Whether does the granular corneal dystrophy indicate for the excimer laser ablation surgery or not]. AB - With the development of excimer laser technologies, the corneal refractive surgical procedures are improved constantly and the indication of excimer laser keratectomy is expanded. In clinic, PRK or LASEK or PTK or LASIK were performed on the eyes of granular corneal dystrophy with refractive error and the early results were satisfied, but the reoccurrence and server opacity of cornea are worried. Is this corneal disease the indication of excimer laser keratectomy? Nowadays, the exact indication for the disease should be declared in clinic. In this article, the customized treatment nomogram for three types of granular corneal dystrophy is explicated according to the clear classification and exact diagnosis on this disease, in order to apply the excimer laser keratectomy reasonably and correctly for the patient approaching the safe, effective and long term satisfactory result. PMID- 22041481 TI - [The clinical study of femtosecond lenticule extraction for myopia]. AB - OBJECTIVE: To evaluate the clinical efficacy, safety and predictability of femtosecond lenticule extraction (FLEx) for myopia. METHODS: This is a prospective Clinical trial involved 10 cases (10 eyes). The patients aged from 18 years old to 53 years old, an average of (34 +/- 11) years old. Femtosecond lenticule extraction (FLEx) was used to treat myopia from -4.88 DS to -9.25 DS, an average of (-6.94 +/- 1.50) DS with cylinder from 0.50 DC to 3.0 um DC an average of (1.28 +/- 0.73)DC. Their corneal thickness were (527.10 +/- 29.05) um in an average. The patients were followed up for 6 to 10 months with visual acuity, manifest refraction, intraocular pressure, wavefront aberration, corneal topography and optical coherence tomography (OCT). SPSS software was used to analysis. RESULTS: FLEx procedure was done well in every patients without any scanning problem. No infection happened to in the trial. The patients' UCVA improved to 0.6 - 1.2 while BCVA improved 0.7 - 1.2 postoperatively. BCVA improved more than 2 lines in 2 eyes whereas 1 line in 2 eyes. No eye lost BCVA. The difference between pre-and postoperative refraction was within +/- 0.75 DS, an average of SE (-0.25 +/- 0.33) DS. No epicenter showed in topography. Spherical aberration increased slightly in 8 eyes but decreased in 2 eyes. OCT showed that stroma bed fit to each other very well. CONCLUSION: Femtosecond lenticule extraction appears to be efficiency, safety and predictable for myopia. Femtosecond lenticule extraction could have a good stroma fit. Its wavefront aberration changes need to further investigation. PMID- 22041482 TI - [Analysis of light scatter changes and relevant factors after laser refractive surgery]. AB - OBJECTIVE: To investigate the changes and relevant factors of forward scatter after Epipolis laser in situ keratomileusis (Epi-LASIK)and laser in situ keratomileusis (LASIK). METHODS: It was a prospective clinical comparative study. 45 patients (45 eyes) were scheduled for Epi-LASIK and 42 patients (42 eyes) for LASIK. Straylight examinations were performed using the C-Quant straylight meter before and 1, 4, 10 months after surgery. The data was analyzed for statistical significance by one-way ANOVA and the correlation was tested by Pearson's test by using SPSS 13.0 software. RESULTS: The straylight values were (0.91 +/- 0.17), (1.03 +/- 0.15), (1.11 +/- 0.13), (1.01 +/- 0.16) of Epi-LASIK group and (0.96 +/ 0.14), (1.05 +/- 0.12), (1.10 +/- 0.12), (0.98 +/- 0.15) of LASIK group preoperatively and 1, 4, 10 months postoperatively respectively, which there were significant increase postoperatively in both groups (F = 12.29, 8.11; P < 0.05). Compared with preoperative values, the changes in straylight values at 1, 4 and 10 months postoperatively were (0.12 +/- 0.18), (0.19 +/- 0.20), (0.08 +/- 0.16) of Epi-LASIK group and (0.09 +/- 0.13), (0.15 +/- 0.17), (-0.01 +/- 0.17) of LASIK group. In Epi-LASIK group, the preoperative refractive error, RBT/CCT, and ablation ratio have significant relevance with straylight values at 4 months postoperatively (r = -0.344, -0.361, 0.361; P < 0.05), no such correlation was found in LASIK group (r = 0.186, 0.162, -0.206; P > 0.05). For corneal haze which was found from 1 to 4 months after Epi-LASIK, grade 2, 1, 0.5 appeared in 1, 2, 4 eyes respectively and the changes of straylight values were 0.52, (0.37, 0.42), (0.06, 0.09, 0.07, 0.17) at 4 months postoperatively. 10 months postoperatively, the increases of straylight values for the eye with grade 2 haze declined from 0.52 to 0.11 after the haze disappeared. CONCLUSION: Straylight values increase significantly at early time after Epi-LASIK and LASIK, but decrease partially as time going. Corneal wound healing response may be the reasons induced the increases of light scatter after Epi-LASIK. For LASIK, flap interface factors may be the reasons. Corneal haze especially above mild grade, can affect the straylight obviously. PMID- 22041483 TI - [Preliminary study on preventive effects of timolol on myopic regression after laser in situ keratomileusis]. AB - OBJECTIVE: To assess the preventive effects of early timolol eye drops application in patients after laser in situ keratomileusis (LASIK). METHODS: Sixty patients (60 eyes) were randomly assigned to the treatment group and the control group. Timolol was administered topically twice per day to the treatment group from the second week through the end of the first month. We observed the changes of intraocular pressure (IOP), spherical equivalent correction (SE), stimulated curvature (Simk), anterior chamber depth (ACD) and different value (Diff) both preoperatively and postoperatively, i.e. before and 1 week after LASIK, 1 month and 3 months after LASIK, respectively. All examinations were completed in person. Independent-samples T test, repeated-measures ANOVA, one-way ANOVA were used for statistical comparisons. Significance level was set to alpha = 0.05. RESULTS: The manifest refraction of treatment group was (-0.07 +/- 0.25) D, (0.04 +/- 0.21) D and (-0.05 +/- 0.12) D, respectively, while the control group was (-0.08 +/- 0.22) D, (-0.15 +/- 0.17) D and (-0.14 +/- 0.18) D, respectively, at 1 week, 1 and 3 months postoperatively. The difference between the two groups was significant (F = 5.68, P < 0.05) regardless of time. The IOP of treatment group was (12.63 +/- 2.56) mm Hg (1 mm Hg = 0.133 kPa), (9.70 +/- 1.88) mm Hg and (11.41 +/- 1.22) mm Hg, respectively, at 1 week, 1 and 3 months postoperatively. The control group did not change significantly throughout follow period. The changes of treatment group was significant in different periods (F = 34.62, P < 0.01). After surgery, the posterior corneal surface of the treatment group displayed mean forward shift of (35.73 +/- 14.55) um and the control group did (45.80 +/- 19.86) um (t = 2.83, P < 0.05). The stimulated curvature (Simk) and anterior chamber depth (ACD) was not significantly different between the two groups at any postoperative visit. CONCLUSIONS: Our prospective study demonstrates that timolol is effective to stabilize the refraction after LASIK. Reduction of IOP and corneal ectasia may play a significant role in preventing myopic regression. PMID- 22041484 TI - [Changes of ocular higher order aberration in keratoconus eyes wearing rigid gas permeable contact lens]. AB - OBJECTIVE: To compare the wavefront characteristics of normal and keratoconus eyes with and without rigid gas-permeable contact lens (RGPCL), and to evaluate the visual quality in keratoconus eyes corrected by RGPCL. METHODS: Retrospective study. Higher order aberrations (HOAs) of 90 eyes in 56 keratoconus patients and 30 eyes of 17 subjects with refractive errors were quantified with a Bausch&Lomb Zywave Wavefront Analyzer. The keratoconus eyes were divided into mild (28 eyes), moderate (33 eyes) and severe (29 eyes) groups. Zernike's polynomial was used to describe the wavefront measurements. Root mean square (RMS) values of the total HOAs, S3, S4, S5, total coma (T. Coma) and total spherical aberrations (T. Sph) were obtained in the same eye with and without contact lenses. We used paired sample t-test and independent-samples t-test to analyze the data. RESULTS: Mean RMS values for High (F = 72.12, P(1) = 0.00), S3 (F = 68.15, P = 0.00), S4 (F = 24.95, P(1) = 0.00), T. Coma (F = 44.67, P = 0.00), T. Sph (F = 28.90, P = 0.01) increased significantly from mild to sever keratoconus eyes RMS values of the total HOAs (t = 4.83), S3 (t = 4.39), total coma (t = 3.71) of refractive error eyes decreased significantly after fitting with RGPCL (P < 0.05). RMS values of the total HOAs (t = 8.27), S3 (t = 8.14), S4 (t = 2.29), total coma (t = 4.38) of mild keratoconus eyes decreased significantly after fitting with RGPCL (P < 0.05) RMS values of the total HOAs (t = 8.03), S3 (t = 7.22), s4 (t = 4.38), S5 (t = 4.53), total coma (t = 5.26) and total spherical (t = 2.77) of moderate keratoconus eyes decreased significantly after fitting with RGPCL (P < 0.05). Every high front-wave aberration of mild keratoconus eyes decreased to refractive error eyes'level after RGPCL fitting. Moderate (t(HOAs) = 0.63, t(s3) = 0.31, t(s4) = 1.70, t(s5) = 0.95, t(coma) = 0.06, t(spherical) = 1.99) and sever keratoconus eyes' higher order aberrations decreased significantly after RGPCL fitting (t(HOAs) = 7.50, t(s3) = 5.25, t(s4) = 5.50, t(s5) = 3.02, t(coma) = 5.90, t(spherical) = 4.60), but they still degrade compared with refractive error eyes (P < 0.05). CONCLUSIONS: RGPCL could reduce high aberrations and improve optical quality in keratoconus eyes. But the visual performance in moderate and severe keratoconus eyes with a RGPCLs is still poorer than that of normal eyes even if the corrected visual acuity is good. PMID- 22041485 TI - [The analysis of axial length changes in the phakic eyes after posterior chamber implantation of lens to correct high myopia]. AB - OBJECTIVE: To definitive axial length measuring mode of the phakic eyes after posterior chamber implantation of lens. METHODS: All patients came from the Ophthalmology Hospital of China Medical University. Seventy patients with 135 eyes, aged 21 - 48 years old. Among this group 28 were male, 53 eyes; 42 were female, 82 eyes. A-ultrasound and IOL-Master was used to measure axial length one week before preoperative and three months after ICL implantation. There are two measuring mode in A-ultrasound and IOL-Master: normal and special. All the results were analysed by the SPSS11.5 statistical methods. RESULTS: (1) preoperative AXL of A-ultrasound and IOL-Master average are: (27.81 +/- 0.22) mm, (28.02 +/- 0.22) mm; (2) postoperative AXL of phakic and Pseudophakic PMMA mode of IOL-Master average are: (28.01 +/- 0.22) mm, (28.12 +/- 0.22) mm; (3) postoperative AXL of normal and special mode of A-ultrasound average are: (27.82 +/- 0.22) mm, (26.40 +/- 0.21) mm. CONCLUSION: According to the different measuring mode, there are some difference of AXL between the preoperative and postoperative ICL. The more accurately measuring mode is IOL-Master phakic mode before and after operation. A-ultrasound normal mode can be used if the lens become so turbid that the AXL can't be obtained by IOL-Master. PMID- 22041486 TI - [Conductive keratoplasty for presbyopia and two years follow-up]. AB - OBJECTIVE: To investigate the effect of conductive keratoplasty (CK) for presbyopia and 2 years follow-up. METHODS: This study is prospective clinical trial. CK was performed on 34 patients for presbyopia, in which 26 hyperopic patients underwent binocular operations and 8 emmetropic patients underwent monocular operation. The following-up time was 24 months. RESULTS: At 24 months postoperatively, for the hyperopia group, binocular uncorrected near visual acuity (33 cm) (5-logMAR) (4.63 +/- 0.12) was increased significantly (t = 9.237, P < 0.001) compared pre-operatively (4.06 +/- 0.15); binocular uncorrected distance visual acuity (4.99 +/- 0.02) was significantly increased (t = 6.718, P < 0.05) compared pre-operatively (4.82 +/- 0.21); for the emmetropia group, binocular uncorrected near visual acuity (33 cm) (5-logMAR) (4.68 +/- 0.16) was increased significantly (t = 10.413, P < 0.001) compared pre-operatively (4.13 +/ 0.18); binocular uncorrected distance visual acuity was same as pre-operative one; compared pre-operatively (+0.97 +/- 0.63D), manifest refractive spherical equivalent was decreased significantly (P < 0.001) to peak value (-1.21 +/- 1.00) D at 1 week, and then regressed to a relative plateau (-0.40 +/- 0.70) D at 24 months; the regressive rate was decreased from (+0.35 +/- 0.44) D/month at 1 month postoperatively to (+0.01 +/- 0.01) D/months at 24 months postoperatively. Contrast sensitivity and glare sensitivity, intraocular pressure, tear break-up time, endothelial cell count, central corneal thickness, stereopsis function and best corrected visual acuity were not significantly changed. CONCLUSIONS: For treatment of presbyopia, CK appeared to be safe, effective, refractive predictable and controllable, and relatively stable at 24 months post operatively. More long-time follow-up is necessary for further evaluation. PMID- 22041487 TI - [Selection of Chinese characters for visual acuity charts using psychophysical methods]. AB - OBJECTIVE: This study investigated the legibility in use of psycho-physical methods to select Chinese characters for visual acuity charts. METHODS: Twenty eight subjects with the raw visual acuity or best corrected visual acuity of 0.11 +/- 0.06 (LogMAR) were recruited for this study. Ninety Chinese characters with similar Fourier frequency spectrum were used as candidates for the selection of visual targets. Thirty-seven Chinese characters with each consisted of horizontal, vertical and oblique strokes were selected from these candidates. Six different-sized BMP images for each selected Chinese character were made based on the average visual acuity threshold of all the selected characters. The accuracy rate for all subjects to read each size of the BMP images was averaged. Graphs correlating the font sizes with the accuracy rates were formed using Weibull function imitation, which provided a visual acuity (VA) threshold and slope for each Chinese character selected. RESULTS: Among the 37 Chinese characters selected, 17 had a VA threshold 6.16 +/- 0.54 (unit: arc) and 20 had a VA threshold of 8.20 +/- 0.71. The slope for characters with low stroke number and medium stroke number was 5.91 +/- 2.18 and 11.18 +/- 3.55, respectively. Based on the similarity in VA thresholds and slopes, 10 Chinese characters were finally determined as the visual targets for a lower stroke-number Chinese visual acuity chart (tb: 5.84 +/- 0.36, beta: 4.72 +/- 0.85). Another 10 characters "rdquo; (tb: 8.38 +/- 0.24, beta: 10.47 +/- 3.9) were determined as the visual targets for a medium stroke-number Chinese visual chart. CONCLUSION: Analysis using Fourier frequency spectrum provides an objective method in the selection of Chinese characters for Chinese visual acuity charts. A psychological test for this selection would further confirm the legibility of the method used in this study. PMID- 22041488 TI - [Research of the change tendency of corneal transplantation indications from 2000 to 2009]. AB - OBJECTIVE: To analyzed retrospectively the indications of corneal transplantations, including penetrating keratoplasty (PKP), lamellar keratoplasty (LKP) and corneal transplantation combined with anterior and posterior segment surgery in Qingdao Eye Hospital, Shandong Eye Institute. And compare the changes of the indications between the first five years and the last five years. METHODS: The patients who received PKP, LKP and corneal transplantation combined with anterior and posterior segment surgeries in Qingdao Eye Hospital, Shandong Eye Institute between January 2000 and December 2009 were reviewed retrospectively. From 2000 to 2009, 3649 cases (3741 eyes) of corneal transplantations have complete data, including male 2518 cases (2582 eyes), female 1131 cases (1159 eyes); PKP 2594 cases (2667 eyes), LKP 1055 cases (1074 eyes). Compare and analysis the indications and its changes between 2000 - 2004 and 2005 - 2009 two periods. RESULTS: During the first period, the leading indications for PKP, in order of decreasing frequency, were purulent keratitis (440 cases, 442 eyes), keratoconus (241 cases, 274 eyes), herpes simplex keratitis (HSK) (229 cases, 229 eyes), the leading indications for LKP were purulent keratitis (221 cases, 221 eyes), corneal burn (including thermal and chemical burn) (106 cases, 106 eyes), others (mainly refers to the phlyctenular keratitis, interstitial keratitis, et al) (79 cases, 79 eyes), the ratio of PKP and LKP is 2.5 to 1.0. During the second period the leading indications for PKP, in order of decreasing frequency, were purulent keratitis (330 cases, 330 eyes), HSK (124 cases, 124 eyes), keratoconus (99 cases, 105 eyes), the leading indications for LKP were purulent keratitis (230 cases, 236 eyes), keratoconus (97 cases, 101 eyes), corneal dystrophy and degeneration (42 cases, 49 eyes), the ratio of PKP and LKP is 1.7 to 1.0. CONCLUSIONS: Purulent keratitis is the main indication of corneal transplantation, the choice of LKP significantly increase. LKP has become the first surgical choice of purulent keratitis and keratoconus. PMID- 22041489 TI - [Relationship between central visual acuity and retinal volume of macular fovea accessed by spectral domain optical coherence tomography in Stargardt disease]. AB - OBJECTIVE: To assess the relationship between central visual acuity and retinal volume of macular fovea in patients with Stargardt disease by spectral-domain optical coherence tomography (SD OCT). METHODS: It was a retrospective case series study. Twenty eyes of 10 patients with Stargardt disease were investigated by three-dimensional spectral-domain optical coherence tomography. SD OCT images were obtained and retrospectively analyzed. The retinal volumes of macular fovea were measured by SD OCT, whose diameters were set as 3 mm and 1 mm separately (volume 3 and volume 1). The retinal thickness of macular fovea (macular thickness) and the width of IS/OS conjunction loss of macular fovea (IS/OS loss) were also measured by SD OCT. We correlated the logMAR BCVA with IS/OS loss, macular thickness, volume 3 and volume 1 by linear regression analysis. RESULTS: LogMAR BCVA was from 0.3 to 1.22. IS/OS loss was from 847 um to 5306 um. Macular thickness was from 20 um to 126 um. Volume 3 and volume 1 was from 1.06 to 1.76 mm(3) and 0.06 to 0.13 mm(3). LogMAR BCVA correlated with the IS/OS loss (r = 0.695, P < 0.05), macular thickness (r = -0.601, P < 0.05), and volume 3(r = 0.725, P < 0.05). LogMAR BCVA did not correlate with volume 1(r = -0.364, P > 0.05). CONCLUSIONS: SD OCT could demonstrate the retinal structure of Stargardt disease clearly. The retinal volume of macular fovea accessed by SD OCT correlated with the visual acuity of Stargardt disease. PMID- 22041490 TI - [Pathological changes of grafted vein after repairing lacrimal canaliculus with autogenous vein graft in rabbits]. AB - OBJECTIVE: To observe the pathological changes of grafted vein after repairing lacrimal canaliculus with autogenous vein graft in rabbits. METHODS: Experimental research. Sixty rabbits were used in the present study. One side of lacrimal canaliculus was disconnected to produce an experimental model. The canaliculus injury was repaired by autogenous vein graft. Pathological changes and cell proliferation of grafted vein segment were observed by routine HE stain and immunohistochemistry. The cell ultrastructure changes were observed by scanning electron microscope at 1, 3, 5, 7, 14 and 28 day after the operation. RESULTS: Experimental models were successfully established in 60 rabbits. Endothelial cells of grafted vein segment gradually disappeared after operation, the vein lumen was covered by canalicular epithelial cells 7 days after the operation. At the same time some variations of epithelial cells and exposed collagen fiber structure in subendothelial layer were found by scanning electron microscope. The vein lumen was completely covered with stratified squamous epithelium 28 days after the operation and no epithelial defect could be found by scanning electron microscope. Inflammatory cell infiltration, smooth muscle cell degeneration and fibroblast proliferation were observed in the subepithelial connective tissues. The reconstruction of propria lamina required more than 28 day. CONCLUSION: After autogenous vein graft repairing lacrimal canaliculus, endothelial cells of grafted vein were replaced by canalicular epithelial cells and the propria lamina of grafted vein segment was reconstructed. PMID- 22041491 TI - [Research of factors related to invasion and metastasis in choroidal melanoma]. AB - OBJECTIVE: To investigate the expression of factors related to invasion and metastasis in choroidal melanoma and to determine their relationships with malignant features. METHODS: The expression of Connexin43 (Cx43), epithelial cadherin (E-cadherin), phosphatidylinositol 3-kinase (PI3K) and connective tissue growth factor (CTGF) in choroidal melanoma and nevi were detected by immunohistochemistry, and the correlation between these factors and clinicopathological features were analyzed. RESULTS: Positive rates of Cx43, E cadherin, PI3K and CTGF were 74.07% (20/27), 44.4% (12/27), 74.07% (20/27) and 66.67% (18/27) in choroidal melanoma tissues, respectively; and 33.33% (5/15), 86.67% (13/15), 33.33% (5/15) and 20.00% (3/15) in the nevi tissues, respectively. There were significant differences in the expression of these markers between the two groups (chi(2) = 5.060, P = 0.024; chi(2) = 5.490, P = 0.019; chi(2) = 5.060, P = 0.024; chi(2) = 6.637, P = 0.010). The expression rates of Cx43 protein were 40% (4/10), 88.89% (8/9) and 100% (8/8) in spindle, mixed and epithelioid cell type, respectively. The expression of these data was related to histological type (chi(2) = 9.874, P = 0.007). The expression rates of PI3K protein were 42.86% (3/7), 75% (9/12) and 100% (8/8), in small, medium and large tumors, respectively, and their expression were co-related to the tumor size (chi(2) = 6.357, P = 0.042). Positive rates of Cx43, E-cadherin, PI3K and CTGF were 50% (6/12), 83.33% (10/12), 50% (6/12) and 41.66% (5/12), respectively, in choroidal melanoma tissues without sclera invasion and were 93.33% (14/15), 40% (6/15), 93.33% (14/15) and 86.67% (13/15), respectively, in choroidal melanoma tissues with violation involved the sclera. There were significant differences of the expression of these markers between the two groups (chi(2) = 4.457, P = 0.016; chi(2) = 3.546, P = 0.028; chi(2) = 4.457, P = 0.016; chi(2) = 4.218, P = 0.019). CONCLUSION: Increased expression of Cx43, PI3K and CTGF and decreased expression of E-cadherin are involved in the processes of invasion and metastasis of choroidal melanoma. PMID- 22041492 TI - [Analysis of authors and endemic distribution of articles published in Chinese Journal of Ophthalmology from 2000 to 2009]. AB - OBJECTIVE: To investigate the authors, the institution and endemic distribution of these authors of Chinese Journal of Ophthalmology, and understand the current situation and problems in the field of Ophthalmology. METHODS: Using the bibliometrics methods, we analyzed the authors, the co-authors and the core authors of papers published between 2000 to 2009. The distribution of institution and region and highly quantitative organization were also analyzed. RESULTS: The 2495 papers were published by the Journal within 10 years. 1091 authors (72.68% of total first authors) published only one paper. There were 705 (28.26%) papers from 105 (7.00%) core authors. There were 2238 papers with one or more co authors, the cooperative rate and degree were 89.70% and 3.91, respectively. 257 papers were written by single author, which accounted for 10.30% of total papers. According to the distribution of Province, Beijing was the first of rank with 726 (29.10%) papers, the second was Guangdong Province by 335 (13.43%) papers, Shanghai was the third with 257 (10.30%) papers. The number of papers from affiliated hospital, provincial or municipal hospitals, county hospitals, military hospitals were 1853 (74.27%), 227 (9.10%), 17 (0.68%) and 164 (6.57%), respectively. 1391 (55.75%) papers were from 16 high-productivity institutes. CONCLUSIONS: Authors of the Chinese Journal of Ophthalmology are from widely distributed area and have a highly cooperative rate, but the distribution was disproportion. The core authors are active and talented, who have a great influence on this journal. The highly-productivity Province are Beijing, Guangdong and Shanghai, even the authors were from widely distributed area. PMID- 22041493 TI - [Protein post-translational modification and age-related cataract]. AB - Cataract is the main cause of vision impairment, and age-related cataract is the most common type of cataract. Protein post-translational modification is the enzymatic processing of a polypeptide chain after translation from messenger RNA and after peptide bond formation has occurred. Deamidation, glycation and oxidation are age-related processes. They can change the structure or solubility of crystallin and result in the opacity of lens while acetylation and methylation may be related to the protection of lens protein. Although much effort has been directed towards slowing progression or preventing the occurrence of cataract, the management of cataract remains surgical. This review deals with the relations between different kinds of protein post-translational modification and age related cataract as well as some protective methods aiming at the process of post translational modification. PMID- 22041494 TI - [Ocular toxicity associated with drugs]. AB - The clinical manifestation of ocular toxicity associated with drugs are various. The ocular toxic manifestations and the degree of impairment are different due to the variety, dose, and routes of exposure and so on. It is difficult to diagnose the cause of the toxicity. If we can't find the toxic factor immediately, stop the damage to the eyes, and treat in time, the patient's vision will be impaired or even lose. This article reviews ocular toxicity caused by drugs, including the variety of drugs, clinical manifestations, etiopathogenesis, diagnosis, treatment and prevention. PMID- 22041495 TI - Prevalence, awareness, treatment, and control of dyslipidemia among adults in Beijing, China. AB - AIM: The present study aimed to determine the up-to-date prevalence, awareness, treatment, and control of dyslipidemia, and their distribution and related influencing factors in adults in Beijing, China. METHOD: A cross-sectional study was conducted in 2008, using a four-stratified cluster sampling. Data from a questionnaire, physical examination, and blood sampling were obtained from 5761 adults aged 18-79 years. RESULTS: The prevalence of high TC, high LDL-C, low HDL C and TG was 12.2%, 17.9%, 12.0% and 15.1%, respectively. The prevalence of dyslipidemia was 35.4% (42.9% in men and 30.1% in women), and was similar in rural (35.3%) and urban (35.8%) areas. Dyslipidemia was associated with male gender, age, a family history of dyslipidemia, education at college or above, current smoker, overweight and obesity, intermediate and high waist circumference, hypertension and diabetes. Among all participants with dyslipidemia, 22.2% were aware of the diagnosis, 10.2% were receiving treatment, and 3.8% had dyslipidemia controlled. The proportion of those aware of their condition and those who were treated increased with age in both sexes. Of those aware of their dyslipidemia, 46.1% were on treatment, 51.0% had modified their lifestyle, and 24.5% were not receiving treatment or modifying their lifestyle. CONCLUSIONS: The major type of dyslipidemia in Beijing is high LDL-C rather than high TG. The prevalence of dyslipidemia is similarly high in rural and urban areas, with low awareness, treatment and control. A comprehensive strategy toward the prevention, screening, treatment, and control of dyslipidemia is needed to slow the epidemic of cardiovascular disease. PMID- 22041496 TI - [Impact factor, H-index and other variable to observe the relative importance of an investigator]. PMID- 22041497 TI - Assessment of sacrificial anode impact by aluminum accumulation in mussel Mytilus edulis: a large-scale laboratory test. AB - Since the early 1960s, the application of aluminum alloy sacrificial anodes to mitigate marine corrosion has been well known. The aim of this work was to study aluminum bioconcentration in Mytilus edulis by an in vitro test performed in two tanks: the first containing non-contaminated water (NCW) and the second containing aluminum-contaminated water (CW) (530 MUg L(-1)) released by sacrificial anode. The mussels were collected and examined over a period of 8 weeks. A comparison between the aluminum concentrations in the digestive glands of mussels from the CW and NCW tanks shows that the highest value (1700 mg/kg d.w.) was found in the CW mussels collected after 13 days. In NCW, the mean aluminum concentration in digestive glands during the test was 281 mg/kg d.w. The rapid concentration decrease in digestive glands is probably due to the inhibition of filtering activity due to valve closure at the high concentration as well as the induction of the detoxification response. PMID- 22041498 TI - Fish consumption and risk of contamination by mercury---considerations on the definition of edible parts based on the case study of European sea bass. AB - In the present study, the risk to humans by consuming European sea bass (Dicentrarchus labrax), captured at three sites along a Hg contamination gradient, was evaluated by comparing muscle and kidney total Hg (T-Hg) levels with the European regulations for marketed fish. Moreover, T-Hg and organic Hg (O Hg) levels in muscle were compared with the Provisional Tolerable Weekly Intake (PTWI) and the Reference Dose (RfD). Although T-Hg levels in muscle were below the European value allowable for marketed fish, kidney's levels were higher than the set value, stressing the importance of redefining the concept of edible tissue and which tissues should be considered. Mercury weekly ingestion in the contaminated areas was higher than the PTWI, and O-Hg daily ingestion rates were higher than the RfD in all sampling sites. Thus, populations consuming sea bass from the contaminated sites may be at risk, with particular relevance for children and pregnant women. PMID- 22041499 TI - Shock priming enhances the efficacy of SSRIs in the foot shock-induced ultrasonic vocalization test. AB - Data on the effect of acutely administered serotonin reuptake inhibitors (SSRIs) in animal anxiety models have been inconsistent. In some of the models these compounds showed anxiolytic properties, while in others they were ineffective or even anxiogenic. In the foot shock-induced ultrasonic vocalization (USV) test in the adult rat, SSRIs were reported to be effective, however, they were only tested with protocols using multiple shocking design. In the present study, anxiolytic effects of various SSRI compounds (sertraline, fluoxetine, paroxetine, escitalopram) were tested in three distinct USV test protocols in comparison with alprazolam and 8-OH-DPAT. In the single shocking protocol, animals were exposed to one shocking session after the drug treatment. In the multiple shocking protocol, rats went through a foot shock priming session before each drug test. On priming days animals received foot shocks without drug treatment. On the test day (the day after), rats received drug treatment and then were shocked again. In the context conditioning protocol animals were exposed to foot shocks on two consecutive days before the drug test. On the third, test day, after drug treatment animals were replaced to the shocking chamber, but this time shocks were not delivered. SSRIs were ineffective using the single shocking protocol. In the context conditioned protocol, all SSRIs showed linear dose-response relationship with ED50 values of 8.5, 2.2, 0.77 and 0.93 mg/kg i.p. for fluoxetine, sertraline, paroxetine and escitalopram, respectively. Using the multiple shocking protocol, SSRIs were only partially effective with maximum inhibitions ranging between 44% and 62%. In contrast to SSRIs, the benzodiazepine anxiolytics, alprazolam showed anxiolytic activity with linear dose-response relationship in all of the test protocols, with ED50 values varying from 1.3 to 4.0 mg/kg i.p. The serotonin 5HT1A receptor antagonist 8-OH-DPAT also showed linear dose-response relationship in all protocols, but this compound was less potent in the single shocking design (ED50 values were 0.27, 0.04 and 0.07 mg/kg i.p. in the single shocking, multiple shocking and context conditioned protocol, respectively). In conclusion, our results show that priming has a major impact on the effectiveness of SSRIs in the USV test, and the three test protocols applied in this study have different predictive and face validity. PMID- 22041500 TI - Dietary choline deficiency causes DNA strand breaks and alters epigenetic marks on DNA and histones. AB - Dietary choline is an important modulator of gene expression (via epigenetic marks) and of DNA integrity. Choline was discovered to be an essential nutrient for some humans approximately one decade ago. This requirement is diminished in young women because estrogen drives endogenous synthesis of phosphatidylcholine, from which choline can be derived. Almost half of women have a single nucleotide polymorphism that abrogates estrogen-induction of endogenous synthesis, and these women require dietary choline just as do men. In the US, dietary intake of choline is marginal. Choline deficiency in people is associated with liver and muscle dysfunction and damage, with apoptosis, and with increased DNA strand breaks. Several mechanisms explain these modifications to DNA. Choline deficiency increases leakage of reactive oxygen species from mitochondria consequent to altered mitochondrial membrane composition and enhanced fatty acid oxidation. Choline deficiency impairs folate metabolism, resulting in decreased thymidylate synthesis and increased uracil misincorporation into DNA, with strand breaks resulting during error-prone repair attempts. Choline deficiency alters DNA methylation, which alters gene expression for critical genes involved in DNA mismatch repair, resulting in increased mutation rates. Any dietary deficiency which increases mutation rates should be associated with increased risk of cancers, and this is the case for choline deficiency. In rodent models, diets low in choline and methyl-groups result in spontaneous hepatocarcinomas. In human epidemiological studies, there are interesting data that suggest that this also may be the case for humans, especially those with SNPs that increase the dietary requirement for choline. PMID- 22041501 TI - Effect of one-year subcutaneous and sublingual immunotherapy on clinical and laboratory parameters in children with rhinitis and asthma: a randomized, placebo controlled, double-blind, double-dummy study. AB - BACKGROUND: It has been reported that both sublingual (SLIT) and subcutaneous (SCIT) allergen-specific immunotherapy have clinical efficacy, yet there are rather few comparative placebo studies of children. We aimed to investigate the clinical and immunological efficacy of mite-specific SLIT and SCIT versus a placebo in rhinitis and asthma in children. METHODS: The outcomes of this 1-year, randomized, placebo-controlled, double-blind, double-dummy study were symptom and medication scores, visual analog scores (VAS), titrated skin prick tests, nasal and bronchial allergen provocation doses, serum house dust mite-specific immunglobulin E (HDM-sIgE), sIgG4, IL-10 and IFN-gamma levels. RESULTS: Clinical and laboratory parameters were evaluated in 30 patients. SCIT significantly diminished symptom and medication scores for rhinitis and asthma (p = 0.03 and p = 0.05 for rhinitis; p = 0.01 and p = 0.05 for asthma) and VAS. SLIT also reduced VAS, symptoms associated with rhinitis and asthma as well as medication usage for rhinitis, but this reduction was not significant when compared with the placebo. Skin reactivitiy to HDM and HDM-sIgE levels was reduced significantly in both immunotherapy groups. Serum IL-10 levels and nasal provocative doses increased significantly with both SCIT and SLIT. Nasal eosinophil increments after nasal challenge decreased with two treatment modes, but bronchial provocative doses and sputum eosinophil increments after bronchial challenge were reduced only with SCIT. In both treatment arms, there was no change in IFN-gamma levels. Serum sIgG4 levels increased significantly only in the SCIT group. CONCLUSION: Based on the limited number of patients at the end of the 1-year immunotherapy, the clinical efficacy of SCIT on rhinitis and asthma symptoms was more evident when compared with the placebo. PMID- 22041502 TI - The synthesis of highly water-dispersible and targeted CdS quantum dots and it is used for bioimaging by confocal microscopy. AB - Synthesis of a highly dispersed hydrophilic CdS nanocrystals and their use as fluorescence labeling for live cell imaging is reported here. By carefully manipulating the surface of CdS nanocrystals, the dispersions of CdS-MAA-PEI-FA nanocrystals with high photostability is prepared. The receptor-mediated delivery of folic acid conjugated quantum dots into folate-receptor-positive cell lines such as CBRH7919 liver cancer cells was demonstrated by confocal microscopy. In the future, the further modified CdS nanoparticles can be used for the tissue imaging in vivo studies. PMID- 22041503 TI - Inclusion complexes of phosphorylated daidzein derivatives with beta cyclodextrin: Preparation and inclusion behavior study. AB - In the present work the feasibility of beta-cyclodextrin in complexation was explored, as a tool for improving the solubility and biological ability of daidzein derivatives. A series of phosphorylated daidzein derivatives featuring different chain lengths were synthesized through a modified Atherton-Todd reaction and their inclusion complexes with betaCD were prepared by coprecipitation method. The inclusion complexation behavior was studied by fluorescence, UV, FT-IR, MS and (1)H NMR. The results showed that only phosphorylated daidzein derivative carrying small substituent group ((C(2)H(5)O)(2)PO) entered the cavity of betaCD and formed 1:1 inclusion complex. The formation constant was 175(mol/L)(-1). PMID- 22041504 TI - Population genetic analysis of Mycobacterium tuberculosis Beijing subgroup strains. AB - Population genetic analysis using variable-number tandem repeat (VNTR) data of 23 loci (15 "optimized MIRU" loci and eight "Beijing option" loci) was done on Mycobacterium tuberculosis Beijing lineage strains isolated in Japan. These strains were divided into Beijing subgroups (B(SUB)) B1-B5 and T2 by minimum spanning tree (MST) analysis. The Phi(PT) values among the B(SUB), a measure of their molecular variance, were significantly different from zero with 999 permutations, indicating the validity of B(SUB) classification using the 23 VNTR loci. Higher number of migrants (Nm) values were observed between B1 and T2, B4 and T2, B3 and T2, and B3 and B4 in a phylogenetic network model reconstructed from previously reported single-nucleotide polymorphism (SNP) data. These B(SUB) combinations, except B3 and B4, shared SNP types; i.e., ST19 was in B1 and T2 and in B4 and T2, and STK was in B3 and T2. These results taken together suggested that shared SNP types were not due to homoplasy, but to strong genetic relatedness between those B(SUB). Haploid genetic diversity and standardized index of association values were different in each B(SUB), indicating that the diversity of each B(SUB) was different. Although the differences in B(SUB) diversity were mostly in accordance with the relative divergence order of the B(SUB) in a phylogenetic network model, the diversity of B4 was biased by a significant increase in the number of strains in this study from patients born after 1964 (Fisher's exact test P<0.01). The different diversity of each B(SUB) indicated increased diversity of Beijing lineage strains, perhaps contributing to the survival and dissemination of these strains. PMID- 22041505 TI - Molecular epidemiological approaches to study the epidemiology of tuberculosis in low-incidence settings receiving immigrants. AB - Although in most wealthy western countries the total incidence of tuberculosis (TB) steadily decreased in the last decades, the proportion of cases in immigrants from high-burden TB countries generally increased and to date a large proportion of all new active cases, often exceeding 50%, occurs among foreign born individuals. In this context, molecular typing of Mycobacterium tuberculosis isolates has significantly contributed to understand the epidemiology of TB, allowing an objective evaluation of the dynamics and the risk of TB importation and transmission within low-incidence host countries. Many molecular studies have shown that a large part of active TB cases in immigrants yield unique, unclustered DNA fingerprints; this finding reflects reactivation of remote latent infections, rather than recent TB infections, and, at the same time, indicates a low rate of disease transmission within the host country. Some studies however express more concern on the basis of higher rates of transmission within the host country with foreign-born index cases. Molecular analysis of isolates also showed that TB infections in migrants may be acquired after arrival in the host country and that TB transmission between foreign-born and autochthonous individuals may occur in both directions. Molecular typing of isolates has been also profitably used to evaluate the diffusion of M. tuberculosis strain families across different geographic areas and human populations and to monitor the diffusion of threatening strains, such as Beijing and/or (multi)drug-resistant strains. To date, based on the contribution of molecular epidemiology, it is possible to adapt or design appropriate strategies for a rational control of TB in low incidence countries. PMID- 22041506 TI - Evidence for inter- and intra-clade recombinations in rabies virus. AB - Homologous recombination is considered rare in negative-strand RNA viruses and has not been reported for rabies virus. In this study, full-length genomes of 44 rabies virus strains were analyzed for potential homologous recombination events. Phylogenetic analysis classified these strains into three clades. By applying six different recombination detection methods, one inter-clade and one intra-clade potential recombination events were identified with high confidence values. Software-predicted recombination break points of the two events were all located within the polymerase gene. This report presents the first evidence suggesting the possibility of homologous recombination in rabies virus, which could provide valuable insights for understanding the diversity and evolution of rabies virus as well as other negative-strand RNA viruses. PMID- 22041507 TI - Intrahost passage alters SigB-dependent acid resistance and host cell-associated kinetics of Listeria monocytogenes. AB - Listeria monocytogenes is a foodborne pathogen that causes gastroenteritis, maternofetal infections and meningoencephalitis in humans. Here we report that an intrahost genome mutation alters bacterial acid resistance and the abilities for replication/invasion in tissue cell culture. Among the L. monocytogenes isolates from the recent outbreak in Japan, we found that one food strain, 668, exhibited the greatest acid resistance, whereas one human clinical strain, 690, sharing identical pulsed-field gel electrophoresis (PFGE) and ribotyping patterns, exhibited an acid-sensitive phenotype. Passage of the 668 food strain through the mouse intestine increased its acid sensitivity without altering the macrogenotypes, indicating intrahost alteration of the bacterial acid-resistant phenotype. Genetic and proteomic analyses revealed a link between acid resistance and SigB (RNA polymerase SigmaB subunit) activity. Compared with the strain 668, the clinical and 4 of 5 mice-passaged strains showed a mutation in the rsbW locus, whose product controls the regulation of SigB activity. Corresponding to the SigB activity, the host-passaged strains had reduced abilities to survive inside macrophages and to invade Caco-2 cells, compared with the food strain 668. Overall, we have demonstrated the first example of a host environment promoting the alteration of SigB-dependent acid resistance and host cell-associated actions of L. monocytogenes. Our study provides new insight into the potential role of intrahost environment in the process of bacterial evolution. PMID- 22041508 TI - In vitro activity of avibactam (NXL104) in combination with beta-lactams against Gram-negative bacteria, including OXA-48 beta-lactamase-producing Klebsiella pneumoniae. AB - The objective of this study was to investigate the in vitro antibacterial activity of avibactam (formerly NXL104) in combination with imipenem, cefepime or ceftazidime against Gram-negative bacteria. Bacterial isolates included: Pseudomonas aeruginosa harbouring PER-1 beta-lactamase (n=14); Acinetobacter baumannii harbouring PER-1, OXA-51 and OXA-58 (n=20); carbapenem-non-susceptible Klebsiella pneumoniae (n=25) and Escherichia coli (n=1) harbouring OXA-48; carbapenem-non-susceptible E. coli (n=1) harbouring both IMP-1 metallo-beta lactamase and extended-spectrum beta-lactamase (ESBL); carbapenem-non-susceptible Serratia marcescens (n=1); and carbapenem-susceptible E. coli (n=20) and K. pneumoniae isolates (n=12) with CTX-M-15 ESBL. Minimum inhibitory concentrations (MICs) of imipenem, cefepime and ceftazidime were determined in combination with 4 mg/L avibactam by the Clinical and Laboratory Standards Institute (CLSI) method on Mueller-Hinton agar. Imipenem/avibactam and ceftazidime/avibactam displayed limited potency against A. baumannii isolates, whereas cefepime/avibactam and ceftazidime/avibactam were active against P. aeruginosa. Klebsiella pneumoniae isolates with OXA-48 beta-lactamase were resistant to imipenem [MIC for 90% of the organisms (MIC(90)) >=4 mg/L]. MIC(90) values for the combination of avibactam 4 mg/L with imipenem, cefepime and ceftazidime were in the susceptible range for all strains (MIC(90)<=0.5mg/L). All E. coli and K. pneumoniae isolates with CTX-M-15 beta-lactamase were inhibited at <=1 mg/L for combinations with avibactam and 100% were susceptible by CLSI breakpoint criteria to imipenem, cefepime and ceftazidime. In conclusion, combinations of imipenem, cefepime and ceftazidime with avibactam may present a promising therapeutic strategy to treat infections due to K. pneumoniae with OXA-48 enzyme as well as K. pneumoniae and E. coli with CTX-M-15 enzyme. PMID- 22041509 TI - Chemotherapy before liver resection of colorectal metastases: friend or foe? AB - OBJECTIVE: We conducted a systematic review of the published literature to critically assess benefits and risks of the use of preoperative chemotherapy in patients presenting with colorectal liver metastases. BACKGROUND: In many centers, chemotherapy is used before hepatic resection of colorectal metastases, even in the presence of a single lesion. Application of chemotherapy requires clear conceptual distinction between patients presenting with resectable lesions (neoadjuvant) versus patients presenting with unresectable lesions, for which chemotherapy is used to reach a resectable situation (downsizing). METHODS: The literature (PubMed) was systematically reviewed for publications related to liver surgery and chemotherapy according to the methodology recommended by the Cochrane Collaboration. RESULTS: For unresectable liver metastases, combination regimens result in enhanced tumor response and resectability rates up to 30%, although the additional benefit from targeted agents such as bevacizumab or cetuximab is marginal. For resectable lesions, studies on neoadjuvant chemotherapy failed to convincingly demonstrate a survival benefit. Most reports described increased postoperative complications in a subset of patients due to parenchymal alterations such as chemotherapy-associated steatohepatitis or sinusoidal obstruction syndrome. CONCLUSION: Preoperative standard chemotherapy can be recommended for downsizing unresectable liver metastases, but not for resectable lesions, for which adjuvant chemotherapy is preferred. PMID- 22041510 TI - Cytology adds value to imaging studies for risk assessment of malignancy in pancreatic mucinous cysts. AB - OBJECTIVE: Evaluate the value of cytology relative to imaging features in risk assessment for malignancy as defined in the Sendai Guidelines. BACKGROUND: The Sendai Guidelines list symptoms, cyst size >30 mm, dilated main pancreatic duct (MPD) >6 mm, mural nodule (MN) and "positive" cytology as high risk stigmata for malignancy warranting surgical triage. METHODS: We reviewed clinical, radiological and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas evaluated in a single tertiary medical center. Cytology slides were blindly re-reviewed and epithelial cells grouped as either benign or high-grade atypia (HGA) [>=high-grade dysplasia]. Histologically, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (in situ and invasive carcinoma). Performance characteristics of cytology relative to other risk factors were evaluated. RESULTS: Dilated MPD, MN, and HGA were independent predictors of malignancy (p < 0.0001), but not symptoms (p = 0.29) or cyst size >30 mm (p = 0.51). HGA was the most sensitive predictor of malignancy in all cysts (72%) and in small (<=30 mm) branch-duct intraductal papillary mucinous neoplasm (BD IPMN; 67%), whereas also being specific (85 and 88%, respectively). MN and dilated MPD were highly specific (>90%), but insensitive (39%-44%). Cytology detected 30% more cancers in small cysts than dilated MPD or MN and half of the cancers without either of these high-risk imaging features. CONCLUSIONS: Cytology adds value to the radiological assessment of predicting malignancy in mucinous cysts, particularly in small BD IPMN. PMID- 22041512 TI - Time for a (re) definition of (recurrent) sigmoid diverticulitis? PMID- 22041514 TI - Risk of cancer in Meckel's diverticulum. PMID- 22041515 TI - Natural orifice transluminal endoscopic surgery: where should we draw the line? PMID- 22041516 TI - Impact of age, and cognitive and coping resources on coping. AB - To explore the predictive value of cognitive and coping resources for problem- and emotion-focused coping with age, we collected data from community-dwelling adults between 20 and 90 years old. We hypothesized that age, perceived stress, self-efficacy, working-memory capacity, and mental flexibility were predictors of coping. We collected data using French versions of the Perceived Stress Scale, General Self-Efficacy Scale, and Way of Coping Checklist. Cognitive assessments comprised the WAIS III digit-span subtest and the Trail Making Test parts A and B. In multivariate analyses, neither working-memory nor mental-flexibility deficit predicted problem-focused coping. Age was found to predict only problem focused coping. Self-efficacy predicted problem-focused coping, and perceived stress predicted emotion-focused coping. Our results confirmed that use of an emotion-focused coping style would not significantly change with age. Problem focused coping increases with age and depends primarily on participants' confidence in their ability to successfully solve problems (i.e., self-efficacy). PMID- 22041517 TI - The planar cell polarity pathway in vertebrate epidermal development, homeostasis and repair. AB - The planar cell polarity (PCP) pathway plays a critical role in diverse developmental processes that require coordinated cellular movement, including neural tube closure and renal tubulogenesis. Recent studies have demonstrated that this pathway also has emerging relevance to the epidermis, as PCP signaling underpins many aspects of skin biology and pathology, including epidermal development, hair orientation, stem cell division and cancer. Coordinated cellular movement required for epidermal repair in mammals is also regulated by PCP signaling, and in this context, a new PCP gene encoding the developmental transcription factor Grainyhead-like 3 (Grhl3) is critical. This review focuses on the role that PCP signaling plays in the skin across a variety of epidermal functions and highlights perturbations that induce epidermal pathologies. PMID- 22041518 TI - Ganglioglioma of the thoracolumbar spinal cord in a patient with neurofibromatosis type 1: a case report and literature review. AB - Gangliogliomas of the spinal cord are rare, and the conus medullaris is an extremely rare site for their occurrence. The authors present a case in which a ganglioglioma was found in the thoracolumbar spinal cord, including the conus medullaris, of a 5-year-old female patient with neurofibromatosis type 1 (NF1) who presented with paraparesis and urinary disturbance. MRI revealed an intramedullary lesion within the thoracolumbar spinal cord, including the conus medullaris, which was surgically removed. Pathological investigation showed a ganglioglioma consisting of glioneuronal tumor cells. This is the first report to provide a pathological description of a spinal cord ganglioglioma in a patient with NF1. Because gangliogliomas usually have a good prognosis following resection, it is important to clearly distinguish them from other NF1-associated lesions, even though ganglioglioma of the thoracolumbar spinal cord, including the conus medullaris, is an extremely rare condition. PMID- 22041519 TI - [Thrombosis and new antithrombotic agents]. PMID- 22041520 TI - Predictive factors for ovarian necrosis in torsion of ovarian tumor. AB - Most cases of ovarian torsion require emergency surgery; the ovary has become necrotic and cannot be conserved. Preoperative determination of the ovarian necrosis extent is difficult but it may increase the likelihood of the ovary conservation. In this study, we retrospectively evaluated the findings in ovarian torsion among patients with ovarian tumors who underwent emergency surgery at a single hospital for possible preoperative indicators of ovarian viability. We thus evaluated 77 patients who were intraoperatively diagnosed with torsion of ovarian tumor between 1995 and 2010. These patients were classified into three groups depending on the postoperative histopathological findings: necrotic, congestive, and normal. Preoperative C-reactive protein (CRP) level, leukocyte count, and body temperature, along with tumor size, degree of torsion, time from the onset of abdominal pain to surgery, and incidence of acute abdomen were compared among the three groups. The sensitivity, specificity, and positive and negative predictive values of the preoperative serum CRP levels for ovarian necrosis were calculated. The CRP level, degree of torsion, and time from the onset of abdominal pain to surgery were significantly higher in the necrotic group than in the normal group. The sensitivity and specificity of the CRP level for necrosis were 35% and 83%, respectively, and positive and negative predictive values were 38% and 82% respectively. The potential for ovary conservation in suspected ovarian torsion should be greater if the tumor is non-malignant, the time from the onset of abdominal pain to operation is short, and the CRP level is < 0.3 mg/dl. PMID- 22041521 TI - A p53 gene mutation in malignant fibrous histiocytoma associated with bone infarction. AB - Transformed sarcomas rarely arise from bone infarct lesions, although the majority of bone sarcomas are primary in origin. However, the pathogenesis of the condition is unknown. In this report, we describe a malignant fibrous histiocytoma with a p53 gene mutation. A 59-year-old woman complained of having pain in her left knee for three months. Plain radiographs of the distal metaphysis of her left femur revealed an ill-defined lytic lesion, which was consistent with a malignant tumor in the infarct lesion. An open biopsy specimen did not show any evidence of malignancy. Immunohistochemical examination of the biopsy specimen failed to show p53 protein-positive cells. However, a mutation in the p53 gene was detected when polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) analysis was performed. A functionally relevant p53 missense mutation in codon 273 of exon 8 [CGT (Arg) -> CAT (His)] was confirmed by direct sequencing. We concluded that this lesion was a malignant bone tumor arising from the bone infarct lesion, and we thus performed a wide resection. The histopathological diagnosis of the resected specimen was that it was a malignant fibrous histiocytoma associated with bone infarction. Immunohistochemistry revealed that the tumor cells were positive for the p53 protein. To our knowledge, our patient is the first patient having a bone infarct-associated sarcoma with a p53 gene mutation. Identification of the p53 mutation helps in diagnosing the malignant transformation of the bone infarct lesion. One pathogenesis of this condition may be a mutation in the p53 gene. PMID- 22041522 TI - Monoamine oxidase A gene polymorphism and suicide: an association study and meta analysis. AB - BACKGROUND: Abnormalities in brain monoamine transmission have been implicated in the pathogenesis of suicidal behavior. Studies examining the association between monoamine oxidase A (MAOA)-uVNTR polymorphism and suicide revealed inconsistent findings. This study aims to evaluate the possible association between the MAOA uVNTR polymorphism and suicidal behaviors by examining our own subjects and conducting a meta-analytic review. METHODS: 373 unrelated psychiatric patients (including 160 suicide attempters and 213 non-suicide attempters) were genotyped for the MAOA-uVNTR polymorphism. A meta-analysis was then performed by pooling data from seven case-control association studies by random effects model. RESULTS: Our results indicate that there is no association between the MAOA-uVNTR polymorphism and suicide attempts in both genders. It also reveals that there is no association with violent suicide attempts. In the meta-analysis, there is no association between the polymorphism and suicidal behaviors. Also, there is no difference in the allelic distribution between psychiatric patients with and without suicidal behaviors. Limitations Our study was constrained by the insufficient information about environmental risk factors of suicide. CONCLUSIONS: Our study is the first one to use meta-analysis in exploring the role of the MAOA-uVNTR polymorphism in suicidal behavior in psychiatric patients. No significant association was found in our study, suggesting MAOA-uVNTR polymorphism is unlikely to contribute significantly to suicide behavior. Further studies investigating the gene-environment interaction or focusing on the genetic risk factors of endophenotypes of suicidal behaviors are warranted. PMID- 22041523 TI - Assessment in vitro of cytogenetic and genotoxic effects of propolis on human lymphocytes. AB - We evaluated the genetic damage by ethanolic extract of propolis (EEP) induced to human lymphocytes which were exposed to increasing concentrations (0-2000MUgml( 1)). The results indicated that EEP reduced significantly the mitotic index (MI) and proliferation index (PI) when high concentrations of EEP were used. Sister chromatid exchange (SCE) rates indicated that EEP could have genotoxic effects at high concentrations. Exposure of the cells to the amount of ethanol used as solvent did not alter either the MI and cell proliferation kinetics (CPK), or the rate of SCE. The results showed: (a) statistical increase in the percentage the cells with CAs and in the frequency of SCE at the highest concentrations, (b) a decrease in MI and in the CPK values was observed, (c) no effect was noticed in negative controls. In conclusion, it can be assumed that high concentrations of EEP have a cyto and genotoxic effect, in vitro, for human peripheral lymphocytes. PMID- 22041524 TI - DSM Science & Technology Awards (south) event 2011: the role of micronutrients in human nutrition. AB - On 21 June 2011, the DSM Science & Technology Awards recognized and rewarded outstanding innovative young scientists active in fundamental and applied research. As in previous years, an international judging committee honored creative and groundbreaking PhD research. Twelve finalists, the top candidates from Switzerland, Austria, France and southern Germany, were invited for the final competition followed by the award ceremony attended by numerous representatives of universities, non-governmental organizations, institutes of technology and industry. PMID- 22041525 TI - Negativity of the basophil activation test in quinolone hypersensitivity: a breakthrough for provocation test decision-making. AB - BACKGROUND: Quinolone hypersensitivity reactions are being more frequently reported. Skin tests in investigations of patients are known to not be fully reliable. The provocation test thus remains the gold standard in the definitive diagnosis of allergy, despite the risks involved. The aim of this study was to evaluate basophil activation tests (BATs) in the diagnosis of immediate-type reactions to quinolones. METHODS: Thirty-four patients who presented an immediate type hypersensivity reaction less than an hour after quinolone administration were studied. The allergologic workup of these patients consisted of a careful clinical history, a skin test and a BAT with the culprit quinolone. If not contraindicated, and in the case of high probability of a nonallergic reaction, provocation tests were performed to assess the nonimmunologic nature of the hypersensitivity. RESULTS: Among the 34 patients studied, 17 (50%) presented a negative BAT to the suspected quinolone, while the other 17 (50%) patients presented a positive BAT for quinolone at the time of their reaction. Among the 17 patients with negative BATs, 15 (2 of whom had had positive skin tests) had quinolone successfully reintroduced. CONCLUSIONS: Our report suggests that the BAT, if negative for the culprit quinolone, is a valuable tool in the decision whether or not to perform provocation tests in patients with a history of immediate-type reaction to quinolones, in order to exclude an allergic reaction. PMID- 22041526 TI - Anti-neutrophilic inflammatory activity of ASP3258, a novel phosphodiesterase type 4 inhibitor. AB - Neutrophil-dominant pulmonary inflammation is an important feature of chronic obstructive pulmonary disease (COPD). Here, we evaluated the in vitro and in vivo anti-neutrophilic inflammatory activities of ASP3258, a novel, orally active, and selective phosphodiesterase (PDE) 4 inhibitor with anti-inflammatory potency comparable to that of second-generation compound roflumilast but with lower emetic activity in vivo. In in vitro experiments using human peripheral blood neutrophils, PDE4 inhibitors ASP3258, cilomilast, and roflumilast inhibited fMLP induced superoxide production in a concentration-dependent manner with IC50 values of 5.0, 96, and 4.7 nM, respectively. ASP3258, cilomilast, and roflumilast also attenuated fMLP-induced neutrophil chemotaxis in a concentration-dependent manner with IC30 values of 18, 270, and 9.7 nM, respectively. In contrast, the glucocorticoid prednisolone inhibited neither superoxide production nor chemotaxis up to 1 MUM. In a rat model of lipopolysaccharide (LPS)-induced lung inflammation, orally administered ASP3258, cilomilast, roflumilast, and prednisolone (at 10 or 30 mg/kg) dose-dependently attenuated pulmonary accumulation of neutrophils. The inhibitory effect of ASP3258 was more potent than cilomilast and almost the same as roflumilast and prednisolone. Treatment with ASP3258 inhibited the elevation of TNF-alpha in the bronchoalveolar lavage fluid following LPS instillation. Histological examination revealed significant inhibition of neutrophil and macrophage infiltration into alveoli by ASP3258. Overall, these findings suggest that ASP3258 has therapeutic potential for treating neutrophilic inflammation such as COPD, partly through direct inhibition of neutrophil activation as well as possibly through inhibition of the TNF-alpha mediated pathway. PMID- 22041527 TI - Ready or not? Here it comes! PMID- 22041528 TI - Hepatitis B and C virus infection and hepatocellular carcinoma in China: a review of epidemiology and control measures. AB - China has one of the highest carrier prevalences of hepatitis B virus (HBV) in the world: nearly 10% of the general population. The disease burden of HBV infection and hepatocellular carcinoma (HCC) is also believed to be among the world's largest, and that of hepatitis C virus (HCV) infection is likely to be substantial as well. However, the epidemiology and measures to control HBV and HCV infection in China remain relatively unknown outside the country. We review the epidemiology of HBV and HCV infection, the disease burden of and risk factors for HCC, and current control measures against HBV and HCV infection in China. We also discuss the relevant literature and implications for future studies of hepatitis and HCC in China. PMID- 22041529 TI - Association between feeling upon awakening and use of information technology devices in Japanese children. AB - BACKGROUND: The objective of this study was to clarify the relationship between feeling upon awakening (FA) and time spent using information technology (IT) devices by children in kindergartens, elementary schools, and junior high schools in Shimane, Japan. METHODS: In October 2008, a self-report survey was distributed to 2075 children in kindergartens (n = 261), elementary schools (n = 1162), and junior high schools (n = 652) in Shimane, Japan. The questionnaire gathered data on sex, school year, feeling upon awakening, and time spent using IT devices after school (television, videos on television, video games, personal computers, and cellular phones). After adjusting for sex and school year, data were analyzed by multivariate logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 2030 children completed this survey (response rate, 97.8%). Negative FA was associated with watching television more than 2 hours/day (OR = 1.51, 95% CI = 1.23-1.85), playing video games more than 30 minutes/day (1.50, 1.20-1.87), and using personal computers more than 30 minutes/day (1.35, 1.04-1.75). CONCLUSIONS: Time spent using IT devices affected the FA of children in kindergarten through junior high school. We propose the development of guidelines regarding the appropriate amount of time this population should spend using IT devices. PMID- 22041530 TI - Effect of the interaction between outdoor air pollution and extreme temperature on daily mortality in Shanghai, China. AB - BACKGROUND: Both outdoor air pollution and extreme temperature have been associated with daily mortality; however, the effect of their interaction is not known. METHODS: This time-series analysis examined the effect of the interaction between outdoor air pollutants and extreme temperature on daily mortality in Shanghai, China. A generalized additive model (GAM) with penalized splines was used to analyze mortality, air pollution, temperature, and covariate data. The effects of air pollutants were stratified by temperature stratum to examine the interaction effect of air pollutants and extreme temperature. RESULTS: We found a statistically significant interaction between PM10/O3 and extreme low temperatures for both total nonaccidental and cause-specific mortality. On days with "normal" temperatures (15th-85th percentile), a 10-ug/m3 increment in PM10 corresponded to a 0.17% (95% CI: 0.03%, 0.32%) increase in total mortality, a 0.23% (0.02%, 0.44%) increase in cardiovascular mortality, and a 0.26% (-0.07%, 0.60%) increase in respiratory mortality. On low-temperature days (<15th percentile), the estimates changed to 0.40% (0.21%, 0.58%) for total mortality, 0.49% (0.13%, 0.86%) for cardiovascular mortality, and 0.24% (-0.33%, 0.82%) for respiratory mortality. The interaction pattern of O3 with lower temperature was similar. The interaction between PM10/O3 and lower temperature remained robust when alternative cut-points were used for temperature strata. CONCLUSIONS: The acute health effects of air pollution might vary by temperature level. PMID- 22041531 TI - White matter hyperintensities and prepulse inhibition in a mixed elderly population. AB - Prepulse inhibition (PPI) of the startle response, a measure for sensorimotor gating, exhibits a relatively high inter-individual variability in elderly subjects. The aim of this study was to investigate whether white matter hyperintensities (WMH), frequently identified on cranial magnetic resonance imaging (MRI) in elderly subjects with and without cognitive impairment, may contribute to variations in PPI. A passive acoustic PPI paradigm was applied in 92 human subjects (53 healthy and 39 patients with Alzheimer's disease or mild cognitive impairment) between 60 and 85years of age. WMH were rated visually on craniel MRI FLAIR images using the Fazekas scale. WMH were identified in 70% of all subjects. The latency to peak of the startle response increased significantly with increasing WMH load, whereas the inhibition of the startle response (PPI) was neither significantly related to the degree of WMH nor to cognitive performance. We conclude that the presence of WMH in the fronto-striatal brain circuit may affect the latency of the startle response, but not information processing in elderly subjects. PMID- 22041533 TI - No seasonal variation in human midbrain serotonin transporter availability in Taiwan. AB - Sunlight exposure is considered responsible for seasonal serotonin changes. Sixty six healthy participants were recruited, and single photon emission computed tomography ([123I]-ADAM SPECT) was used to investigate the association between serotonin transporter (SERT) availability and duration of sunlight exposure in Taiwan, a subtropical country. No significant correlation between SERT availability and the duration of sunlight exposure was found. PMID- 22041532 TI - Amygdalar, hippocampal, and thalamic volumes in youth at high risk for development of bipolar disorder. AB - Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are at significantly high risk for developing BD. As we have previously shown amygdalar reductions in pediatric BD, the current study examined amygdalar volumes in offspring of parents (BD offspring) who have not yet developed a full manic episode. Youth participating in the study included 22 BD offspring and 22 healthy controls of comparable age, gender, handedness, and IQ. Subjects had no history of a manic episode, but met criteria for ADHD and moderate mood symptoms. MRI was performed on a 3T GE scanner, using a 3D volumetric spoiled gradient echo series. Amygdalae were manually traced using BrainImage Java software on positionally normalized brain stacks. Bipolar offspring had similar amygdalar volumes compared to the control group. Exploratory analyses yielded no differences in hippocampal or thalamic volumes. Bipolar offspring do not show decreased amygdalar volume, possibly because these abnormalities occur after more prolonged illness rather than as a preexisting risk factor. Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD. PMID- 22041534 TI - The implication of functional connectivity strength in predicting treatment response of major depressive disorder: a resting EEG study. AB - Predicting treatment response in major depressive disorder (MDD) has been an important clinical issue given that the initial intent-to-treat response rate is only 50 to 60%. This study was designed to examine whether functional connectivity strengths of resting EEG could be potential biomarkers in predicting treatment response at 8 weeks of treatment. Resting state 3-min eyes-closed EEG activity was recorded at baseline and compared in 108 depressed patients. All patients were being treated with selective serotonin-reuptake inhibitors. Baseline coherence and power series correlation were compared between responders and non-responders evaluated at the 8th week by Hamilton Depression Rating Scale. Pearson correlation and receiver operating characteristic (ROC) analyses were applied to evaluate the performance of connectivity strengths in predicting/classifying treatment responses. The connectivity strengths of right fronto-temporal network at delta/theta frequencies differentiated responders and non-responders at the 8th week of treatment, such that the stronger the connectivity strengths, the poorer the treatment response. ROC analyses supported the value of these measures in classifying responders/non-responders. Our results suggest that fronto-temporal connectivity strengths could be potential biomarkers to differentiate responders and slow responders or non-responders in MDD. PMID- 22041535 TI - Lateral ventricle volume and psychotic features in adolescents and adults with bipolar disorder. AB - This magnetic resonance imaging study demonstrates increased lateral ventricle volume (LVV) in adolescents and adults with bipolar disorder (BD) with psychotic symptoms, but not without psychosis, compared to healthy adolescents and adults. This suggests LVV is a morphologic feature associated with psychosis in BD, present by adolescence. PMID- 22041536 TI - Supreme Court asked to decide future of US health care. PMID- 22041537 TI - The World Cancer Declaration: from resolution to action. PMID- 22041538 TI - Pharmacokinetics of gefitinib and erlotinib. PMID- 22041539 TI - The MARS feasibility trial: conclusions not supported by data. PMID- 22041541 TI - Pitfalls in the assessment of prognostic factors. PMID- 22041542 TI - Herbal medicine regulation: buyers beware. PMID- 22041543 TI - Reduction of serum lipids by the intake of the extract of garlic fermented with Monascus pilosus: a randomized, double-blind, placebo-controlled clinical trial. AB - BACKGROUND & AIMS: A dietary supplement containing garlic fermented with Monascus pilosus (MGFE) may be useful to decrease the lipid concentrations in serum without serious adverse effects. The aim of the study was to assess whether MGFE decreases serum lipid contents in volunteers with mild hyperlipidemia in a randomized, double-blind, placebo-controlled, parallel-group trial. METHODS: Healthy subjects (n = 55) with serum triglyceride concentrations of 120-200mg/dL were randomly assigned to take either MGFE or placebo capsules for 12 wk. RESULTS: A borderline, but not significant effect, to decrease triglyceride concentrations in serum (approximately 15% reduction at maximum, P = 0.062, in time * treatment interaction effect) was observed by the MGFE intake for 12 wk. The decreased reading exhibited a significant difference at wk-8 between the MGFE and placebo groups (unpaired t test, P = 0.007). The total cholesterol (P = 0.003) and LDL cholesterol (P = 0.001) contents in the serum and the LDL/HDL ratio (P < 0.001) were significant in time * treatment interaction effects by the MGFE intake. However, no alteration in the body fat percentage and abdominal circumference was observed. CONCLUSIONS: The intake of MGFE decreased triglyceride and cholesterol in serum with no appreciable adverse effects in normal to mildly hyperlipidemic individuals, suggesting that it may be effective to improve and prevent the metabolic syndrome. This clinical trial was registered with Clinicaltrials.gov as NCT00938249. PMID- 22041544 TI - Efficacy of Seprafilm(r) in abdominal surgery for ventriculoperitoneal shunt malfunction: a report of two pediatric cases. AB - Temporary external drainage with adequate antibiotic treatment followed by ventriculoperitoneal (VP) shunt reinsertion is necessary to treat VP shunt malfunction with infection. In surgeries for VP shunt reinsertion, the key factors that determine whether the reinserted VP shunt will function sufficiently are adequate adhesiolysis and safe placement of the VP shunt within a satisfactory peritoneal location. Based on these factors, the prevention of postoperative adhesions after surgery for VP shunt malfunction is very important. We present two cases of shunt malfunction related to infection and report their successful treatment using Seprafilm(r). Seprafilm may improve the safety of VP shunt reinsertion and preserve the function of the reinserted VP shunt after VP shunt malfunction with infection. PMID- 22041545 TI - Cause, care, cure: research priorities for Alzheimer's disease and related dementias. AB - Part of Ontario's strategy on Alzheimer's disease and related dementias (ADRD) was to develop research priorities and recommend strategies for building research capacity. The process to achieve these objectives included an environmental scan, key informant interviews, surveys, and a consensus workshop; this process involved over 100 researchers, clinicians, persons with early dementia, and family caregivers. This article describes the process undertaken, key issues identified, and recommendations for research priorities and for building research capacity; and provides a strategic direction for dementia research in Ontario that is relevant for other jurisdictions. ADRD research in all aspects is required to advance knowledge of ADRD cause, care, and cure; gaps currently exist in understanding effective approaches to care and knowledge transfer. Capacity for high-calibre research hinges on maintaining attractive career paths for researchers, solid infrastructures, and strong partnerships. For research to inform policy and practice, better mechanisms are needed for knowledge exchange. PMID- 22041546 TI - Recognition of greater diversity of Bacillus species and related bacteria in human faeces. AB - In a study looking at culturable aerobic Actinobacteria associated with the human gastrointestinal tract, the vast majority of isolates obtained from dried human faeces belonged to the genus Bacillus and related bacteria. A total of 124 isolates were recovered from the faeces of 10 healthy adult donors. 16S rRNA gene sequence analyses showed the majority belonged to the families Bacillaceae (n=81) and Paenibacillaceae (n=3), with Bacillus species isolated from all donors. Isolates tentatively identified as Bacillus clausii (n=32) and Bacillus licheniformis (n=28) were recovered most frequently, with the genera Lysinibacillus, Ureibacillus, Oceanobacillus, Ornithinibacillus and Virgibacillus represented in some donors. Phenotypic data confirmed the identities of isolates belonging to well-characterized species. Representatives of the phylum Actinobacteria were recovered in much lower numbers (n=11). Many of the bacilli exhibited antimicrobial activity against one or more strains of Clostridium difficile, Clostridium perfringens, Listeria monocytogenes and Staphylococcus aureus, with some (n=12) found to have no detectable cytopathic effect on HEp-2 cells. This study has revealed greater diversity within gut-associated aerobic spore-formers than previous studies, and suggests that bacilli with potential as probiotics could be isolated from the human gut. PMID- 22041547 TI - Discovery of novel biopreservation agents with inhibitory effects on growth of food-borne pathogens and their application to seafood products. AB - Selection of protective cultures is relevant in order to biopreserve and improve the functional safety of food products, mainly through inhibition of spoilage and/or pathogenic bacteria. Accordingly, the present study investigated potential applications of lactic acid bacteria (LAB) in the biopreservation of fish and shellfish products. For this purpose, a collection of 84 LAB strains isolated from sea bass (Dicentrarchus labrax) and sea bream (Sparus aurata) was identified and characterized for their inhibitory activities against the most relevant seafood-spoilage and pathogenic bacteria potentially present in commercial products. The bioactive strains belonged to the genus Enterococcus and exhibited inhibition against Carnobacterium sp, Bacillus sp, Listeria monocytogenes, Aeromonas salmonicida, Aeromonas hydrophila and Vibrio anguillarum. Treatment of cell-free extracts of the LAB strains with proteases revealed the proteinaceous nature of the inhibition. Interestingly, the cell-free extracts containing bacteriocins remained 100% active after treatment up to 100 degrees C for 30 min or 121 degrees C for 15 min. Molecular analysis led to identification of the bacteriocins investigated, including enterocins A, B, L50 and P. All of these proteins demonstrated remarkable anti-Listeria activity and were found to be heat resistant small class IIa bacteriocins. The results presented in this work open the way for potential applications of these LAB strains to the biopreservation of minimally-processed seafood products. PMID- 22041548 TI - From metallic cages to transient bioresorbable scaffolds: change in paradigm of coronary revascularization in the upcoming decade? PMID- 22041549 TI - Psychosis, depression, and high risk for sudden cardiac death: time for co operation between psychiatrists and cardiologists. PMID- 22041550 TI - Left atrial appendage closure: a percutaneous transcatheter approach for stroke prevention in atrial fibrillation. AB - Atrial fibrillation is a frequent cause of stroke; in the elderly, more than 20% of strokes are attributed to this common arrhythmia. Anticoagulation with warfarin reduces the risk of stroke by ~60%; however, a large proportion of patients with atrial fibrillation do not receive this treatment because of relative/absolute contraindications. Moreover, patients often discontinue warfarin for a variety of reasons and chronic warfarin administration rates remain suboptimal. Although the compliance with anticoagulation may improve with novel anticoagulants and bleeding risk can be somewhat reduced when compared with warfarin, there is still a progressive increase in bleeding complications over time. Accordingly, new approaches for stroke prevention in these patients are being explored and tested. In transoesophageal echocardiographic (TEE) studies, more than 90% of thrombi were found in the left atrial appendage (LAA) in non valvular atrial fibrillation, and transcatheter LAA closure is developed and examined as a novel approach to reduce the risk of stroke in these patients. The PROTECT-AF study provides first evidence from a randomized clinical trial that a strategy of LAA occlusion using the Watchman device can be non-inferior to anticoagulation with warfarin for a combined endpoint in patients with non valvular atrial fibrillation (mean CHADS(2) score 1.8). In successfully occluded patients fulfilling TEE criteria (86%), warfarin was stopped after 45 days, followed by aspirin and clopidogrel for 6 months after randomization and subsequently aspirin. The PREVAIL trial is further evaluating this concept. Limited data are available for another LAA occlusion system, the Amplatzer Cardiac Plug (ACP) device, for which the ACP trial has been initiated. Left atrial appendage occlusion needs to be performed with meticulous care by experienced operators because periprocedural complications such as pericardial effusion or stroke have been documented. With increased operator experience and technical improvements of the device, these complications can be minimized. PMID- 22041551 TI - De-risking the clinical development of cholesteryl ester transfer protein inhibitors: how much is good enough? PMID- 22041552 TI - An unusual cause of embolic myocardial infarction. PMID- 22041553 TI - Safety and efficacy of a pharmaco-invasive reperfusion strategy in rural ST elevation myocardial infarction patients with expected delays due to long distance transfers. AB - AIMS: To determine the safety and efficacy of a pharmaco-invasive reperfusion strategy utilizing half-dose fibrinolysis combined with transfer for immediate percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients presenting to remote rural hospitals. Primary PCI is preferred for STEMI if performed in a timely manner. However, <20% of STEMI patients transferred for PCI in the USA have door-to-balloon times <2 h. METHODS AND RESULTS: Prospective data from the Level 1 MI programme were analysed. All STEMI patients presenting to the Minneapolis Heart Institute or 31 referral hospitals received aspirin, clopidogrel, and unfractionated heparin (UFH) at the presenting hospital and those presenting to hospitals >=60 miles away also received half dose fibrinolytic with transfer for immediate PCI. From April 2003 through December 2009, we enrolled 2634 consecutive STEMI patients in the Level 1 MI database including 660 transferred from remote hospitals utilizing pharmaco invasive therapy and 600 patients who presented directly to the PCI centre. There were no significant differences in 30-day mortality (5.5 vs. 5.6%; P= 0.94), stroke (1.1 vs. 1.3%; P= 0.66) or major bleeding (1.5 vs. 1.8%; P= 0.65), or re infarction/ischaemia (1.2 vs. 2.5%; P= 0.088) in patients receiving a pharmaco invasive strategy compared with patients presenting directly to the PCI centre, despite a significantly longer door-to-balloon time. CONCLUSION: Within a regional STEMI system of care, half-dose fibrinolysis combined with immediate transfer for PCI may be a safe and effective option for STEMI patients with expected delays due to long-distance transfer. PMID- 22041554 TI - Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are beneficial in normotensive atherosclerotic patients: a collaborative meta analysis of randomized trials. AB - AIMS: It is unclear whether angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) are beneficial in individuals with, or at increased risk for, atherosclerotic vascular disease who are normotensive. METHODS AND RESULTS: Two investigators independently searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from 1980 to 2011, bibliographies, and contacted primary study authors for randomized placebo controlled outcome trials evaluating ACE-I or ARB which enrolled at least 1000 patients with, or at increased risk for, atherosclerotic vascular disease and followed them for at least 12 months. We approached all eligible trials to obtain data stratified by baseline systolic pressures. We pooled data from 13 trials of 80 594 patients; outcomes included 9043 all-cause deaths, 5674 cardiovascular deaths, 3106 myocardial infarctions, and 4452 strokes. Angiotensin-converting enzyme inhibitors or ARB reduced the composite primary outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke by 11% (95% confidence interval 7-15%), with no variation in efficacy across baseline systolic blood pressure strata. In patients with baseline systolic pressure <130 mmHg, ACE-I or ARB reduced the composite primary outcome by 16% (10-23%) and all cause mortality by 11% (4-18%)-this benefit was consistent across all subgroups examined including those without systolic heart failure (OR: 0.81, 95% CI: 0.75 0.88) and those without diabetes (OR: 0.79, 95% CI: 0.70-0.89). CONCLUSION: Angiotensin-converting enzyme inhibitors or ARB are beneficial in patients with, or at increased risk for, atherosclerotic disease even if their systolic pressure is <130 mmHg before treatment. PMID- 22041555 TI - Involvement of estrogen receptors in the resveratrol-mediated increase in dopamine transporter in human dopaminergic neurons and in striatum of female mice. AB - Treatment with resveratrol (RSV) has been shown to protect vulnerable neurons after various brain injuries and in neurodegenerative diseases. The mechanisms for the effects of RSV in brain are not fully understood, but RSV may affect the expression of various gene products. RSV is structurally related to the synthetic estrogen, diethylstilbestrol so the effects of RSV may be gender-specific. Here we studied the role of RSV in the regulation of dopamine transporter (DAT) in the striatum using male and female mice. The basic levels of DAT in the striatum showed no sex difference, but the levels increased significantly by RSV (20 mg/kg i.p.) in female but not in male mice. Pretreatment of mice with the selective estrogen receptor (ER), ERalpha- and ERbeta antagonist ICI 182,780, led to a complete block of RSV effect on DAT protein levels, suggesting that ERs are involved in the up-regulation of DAT by RSV. Similar data was also obtained in culture using human MESC2.10 and mouse SN4741 dopaminergic cells after treatment with RSV. Data further showed that RSV specifically induced gene transcription of DAT in the dopaminergic cells. These results show that estrogen receptors are involved in the up-regulation of DAT by RSV in the dopaminergic neurons, demonstrating a sex-dependent effect of RSV in the brain that may be of clinical importance. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22041556 TI - [Contributions to translational medicine from cancer epidemiological and etiological studies]. PMID- 22041557 TI - [Hybrid Escherichia coli: the pathogen of 2011 Germany pandemic]. PMID- 22041558 TI - [The association between polymorphism of transforming growth factor-beta1 and radiochemotherapy response and survival in esophageal squamous cell carcinoma patients]. AB - OBJECTIVE: To evaluate the association between polymorphism of transforming growth factor-beta1 (TGF-beta1)-509C/T and radiochemotherapy response and survival in esophageal squamous cell carcinoma (ESCC) patients. METHODS: The genotype of TGF-beta1-509C/T was detected by polymerase chain reaction-based restriction fragment length polymorphism assay (PCR-RFLP) in 230 ESCC patients receiving radiotherapy alone or in combination with chemotherapy. Unconditional multivariate logistic regression analysis was done to estimate adjusted odds ratios (ORs) along with the corresponding 95% confidence intervals (CIs) for the polymorphism and radiochemotherapy response. The associations between overall survival time or hazard ratio (HR) of ESCC patients and genetic variation or the clinical data were estimated by applying univariate and multivariate Cox regression analyses. RESULTS: Among 208 patients with upper gastrointestinal contrast assessment, 87 cases were susceptible to radiochemotherapy treatment and the TGF-beta1-509CC, CT and TT genotype patients were 17 (19.5%), 48 (55.2%) and 22 (25.3%), respectively. Among the patients who were insensitive to radiochemotherapy treatment (n = 121), the TGF-beta1-509CC, CT and TT genotype patients were 39 (32.2%), 54 (44.6%) and 28 (23.2%), respectively. Compared with TGF-beta1-509CC genotype, the CT and TT genotype carriers had a significantly better treatment response (adjusted OR = 2.07, 95%CI, 1.05 - 4.09, P = 0.036). The median survival time of CC genotype patients was 17.0 (95%CI, 12.0 - 23.0) months, CT genotype patients was 22.0 (95%CI, 16.0 - 33.0) months and TT genotype patients was 25.0 (95%CI, 15.0 - 41.0) months. Compared to CC genotype patients, the survival time difference of CT and TT group was close to the statistical break point (P = 0.063). Our data showed that the subjects with CT or TT genotype had an decreased HR respectively as compared with those with CC genotype (CT, adjusted HR = 0.81, 95%CI, 0.52 - 1.24; TT, adjusted HR = 0.86, 95%CI, 0.65 - 1.12), but the difference was not statistically significant (P > 0.05). However, tumor location, clinical stage and radiochemotherapy response affected the overall survival time of the patient significantly (adjusted HR = 1.28, 95%CI: 1.01 - 1.61, P = 0.040; 1.49, 95%CI, 1.17 - 1.88, P = 0.001; 1.55, 95%CI, 1.06 - 2.26, P = 0.023, respectively). CONCLUSION: These results suggest that TGF-beta1 509C/T polymorphisms were associated with radiochemotherapy for esophageal squamous cell carcinoma which might be genetic markers for prediction of the radiochemotherapy response in ESCC patients. PMID- 22041559 TI - [The correlation between polymorphisms of Toll-like receptor 2 and Toll-like receptor 9 and susceptibility to gastric cancer]. AB - OBJECTIVE: To explore the relationship between the polymorphisms of Toll-like receptor 2 (TLR2) and TLR9 and the susceptibility to gastric cancer. METHODS: A population-based case-control study was conducted at Linqu county, Shandong province, China, including a total of 248 cases of gastric cancer. Another total of 496 age and sex-matched controls were randomly selected from the same cohorts. TLR2 rs3804099 and TLR9 rs187084 were detected by polymerase chain reaction restriction fragment length polymorphism method. Odds ratios (ORs) and 95% confidence interval (CI) were computed from logistic regression models after adjusting for age, sex, Helicobacter pylori (H. pylori) infection and smoking status. RESULTS: The frequencies of TT, TC and CC genotype on TLR2 rs3804099 in control group were 43.5% (216/496), 46.6% (231/496) and 9.9% (49/496), respectively; whereas those in case group were 53.2% (132/248), 39.9% (99/248) and 6.9% (17/248), respectively. Significant differences in the frequencies of TLR2 rs3804099 were found between case and control groups (chi(2) = 6.665, P = 0.036). It was found that compared with the TT genotype, TC + CC genotype carriers obviously less susceptible to gastric cancer (OR = 0.68, 95%CI: 0.50 - 0.93). Joint effects analysis indicated that the TLR2 rs3804099 TT genotype carriers and H.pylori infectors had higher susceptibility to gastric cancer(OR = 3.42, 95%CI: 2.16 - 5.42), compared with TC + CC genotype carriers and non H.pylori infection group. The frequencies of TT, TC and CC genotype on TLR9 rs187084 in control group were 33.3% (165/496), 49.0% (243/496) and 17.7% (88/496), respectively; whereas those in case group were 35.9% (89/248), 50.0% (124/248) and 14.1% (35/248), respectively. No significant association with gastric cancer was observed for TLR9 rs187084 polymorphism (chi(2) = 1.684, P = 0.431). CONCLUSION: Our findings indicate that TLR2 rs3804099 is closely associated with susceptibility to gastric cancer. PMID- 22041560 TI - [The relationship between gene polymorphism of telomerase reverse transcriptase and susceptibility to hepatocellular carcinoma]. AB - OBJECTIVE: To explore the correlation between single-nucleotide polymorphisms (SNPs) of telomerase reverse transcriptase (TERT) rs2736098 and rs2736100 and the susceptibility to hepatocellular carcinoma (HCC). METHODS: This case-control study design included 1300 diagnosed HCC patients with HBsAg positive and 1344 HBsAg positive people as control-group.rs2736098 and rs2736100 on TERT were selected as research sites, whose polymorphisms were detected by TaqMan allelic discrimination assay. The OR values (95%CI) were calculated by logistic regression to compare the correlation between different genotype and susceptibility to HCC. RESULTS: The distribution frequencies of three genotypes as GG, AG and AA on rs2736098 were separately 39.3% (500/1273), 44.2% (563/1273) and 16.5% (210/1273) in case group; while respectively 39.6% (526/1328), 45.5% (604/1328) and 14.9% (198/1328) in control group. The distribution frequencies of three genotypes as AA, AC and CC on rs2736100 were separately 33.7% (428/1269), 49.9% (633/1269) and 16.4% (208/1269) in case group; while respectively 34.0% (449/1322), 49.2% (651/1322) and 16.8% (222/1322) in control group. The multi variates logistic regression analysis showed that there was no significant difference between rs2736098 mutated A carriers and genotype GG carriers in the susceptibility to HCC after adjusting by age, sex, smoking and drinking factors (rs2736098, AA + AG vs GG: adjusted OR = 1.00 (95%CI: 0.86 - 1.18)); and there was no significant different between rs2736100 mutated C carriers and genotype AA carriers in the susceptibility to HCC either (AC + CC vs AA: adjusted OR = 1.03 (95%CI: 0.87 - 1.22)). CONCLUSION: The polymorphisms of rs2736098 and rs2736100 on TERT may not play a landmark role in susceptibility to HCC among Chinese population. PMID- 22041561 TI - [Downregulation of chromobox protein homolog 7 expression in multiple human cancer tissues]. AB - OBJECTIVE: To investigate the relationship between chromobox protein homolog 7 (cbx7) expression and the occurrence and development of colorectal carcinoma (CRC), gastric carcinoma (GC) and hepatocarcinoma (HCC) tissues. METHODS: The samples of neoplastic tissues and the corresponding cutting-edge normal tissues from 22 cases of CRC, 20 cases of GC, 30 cases of HCC were surgically collected. Level of cbx7 mRNA was detected with a fluorescent quantitative RT-PCR assay, and the correlationship among expression of cbx7 mRNA, the patients' clinicopathologic features and the surviving time after surgery was analyzed. RESULTS: The relative copy number of cbx7 mRNA in carcinomas and the normal tissues was 0.010 +/- 0.015 vs 0.053 +/- 0.042 for CRCs, 0.197 +/- 0.195 vs 1.891 +/- 1.254 for GCs, and 0.008 +/- 0.008 vs 0.030 +/- 0.021 for HCCs, respectively. Compared with the corresponding normal tissues, cbx7 expression was significantly downregulated in CRCs, GCs, and HCCs (t = -7.351, -5.417 and -6.680, respectively, P < 0.01). The expression of cbx7 mRNA in CRCs had significant differences not only between two age groups (the relative copy number of cbx7 mRNA in age > 55 group was 0.007 +/- 0.015, but 0.017 +/- 0.012 in age <= 55 group, t = -2.586, P = 0.022); but also between vascular embolus-positive and negative groups (the level of cbx7 mRNA in positive and negative group was 0.022 +/- 0.021 vs 0.006 +/- 0.011, t = -3.175, P = 0.010). The area under the receiver operating characteristics (ROC) curve is 0.769 (P = 0.033). when the Cut-off value of the relative copy number of cbx7 mRNA was 0.002 in CRCs. The values less than 0.002 were defined as low expression. The CRC patients with low expression of cbx7 had a shorter overall survival time; whose 5 years survival rate was only 30.8% (4/13); while the rate was 77.8% (7/9) in high expression of cbx7 group. The difference had statistical significance (chi(2) = 4.329, P = 0.037). The similar differences could not be found among GC and HCC patients. CONCLUSION: Downregulation of cbx7 expression was very common among multiple carcinomas cases, and the downregulation influenced the prognosis of CRC patients. PMID- 22041562 TI - [Primary evaluation of a mass screening program for colorectal tumor in China]. AB - OBJECTIVE: To evaluate a colorectal cancer screening program by tumor detection rate and discussing its application values. METHOD: In total, 43 713 subjects were recruited in the screening program who were the registered people aged 40 - 74 in Xiacheng and Jiashan during year 2007 - 2009. The first screening involved questionnaire survey of colorectal cancer related risk factors and fecal occult blood test (FOBT), colonoscopy was performed when a positive result was observed in the first screening. If polyps were found during colonoscopy, biopsy and pathological diagnosis were carried out. The screening data were analyzed and the tumor detection rate was calculated according to age or sex. RESULTS: 6489 subjects (14.85%) belonged to the high risk group of colorectal cancer in the first screening, in which 4701 subjects finished complete colonoscopy. Finally, 569 colorectal neoplasm were diagnosed, the detection rate was 12.10% (95%CI: 11.17% - 13.04%). It included 52 colorectal cancer (1.11%, 95%CI: 0.81% - 1.41%), 183 advanced adenoma (3.89%, 95%CI: 3.34% - 4.45%), 334 non-advanced adenoma (7.10%, 95%CI: 6.37% - 7.84%). The highest detective rate was observed in male group that aged 70 - 74 (22.81%, 95%CI: 16.98% - 28.70%), the lowest detective rate was observed in female group aged 40 - 44 (2.49%, 95%CI: 0.79% - 4.20%). CONCLUSION: The current colorectal cancer screening program in China works well, but the revision of the program is necessary. PMID- 22041563 TI - [Analysis of sensitivity and specificity of sputum cytology screening for lung cancer with different positive criteria]. AB - OBJECTIVE: To discuss the effect of different positive criteria on the sensitivity and specificity of sputum cytology screening for lung cancer among Yunnan tin miners. METHODS: 9223 Yunnan tin miners who received at least one annual sputum cytology screening for lung cancer during the period between 1992 and 1999 were recruited in the study. At time of enrollment, all participants were aged over 40 years old, had at least 10 years of employment as an underground miner and(or) smelter, and had not been diagnosed with malignancy. In our study, a true positive was categorized as having at least one prior positive sputum screening and a diagnosis of lung cancer, while a true negative, by our definition, signified negative sputum examinations and no diagnosis of lung cancer during the follow up time. Based on different positive criteria, sensitivity and specificity of sputum cytology were computed and receiver operating characteristic (ROC) curve analysis was conducted. Z statistic was used to test the differences of the area under ROC based on Hanley and McNeil method. RESULTS: By the end of following up on December 31, 2001, a total 500 lung cancer cases were diagnosed among 9223 participants: most were squamous cell carcinoma (55.8% (222/398)) and central lung cancers (68.5% (316/461)). 150 lung cancer cases had a previous positive sputum screening result. When positive criteria were taken as grave atypical metaplasia, moderate atypical metaplasia and slight atypical metaplasia, the corresponding sensitivities were 30.0% (150/500), 36.4% (182/500), 53.0% (265/500) respectively; while the corresponding specificities were 98.9% (8628/8723), 95.1% (8611/8723), 77.9% (7033/8723) respectively. The areas under ROC curve according to different positive criterias were 0.645 (95%CI: 0.635 - 0.654), 0.657 (95%CI: 0.668 - 0.667), 0.655 (95%CI: 0.645 - 0.664) respectively. There were no significant differences found in the comparisons between grave and moderate atypical metaplasia, grave and slight atypical metaplasia, moderate and slight atypical metaplasia(Z statistics were 0.780, 0.645, 0.209 respectively, all P values > 0.05). CONCLUSION: While the standard of positive criteria for diagnosis of lung cancer decreased, the sensitivity of sputum cytology screening increased and the specificity decreased. Since there were no significant differences of accuracy for different positive criteria. PMID- 22041564 TI - [Survey and analysis of ethyl carbamate in commercial fermented foods in Hangzhou in 2010]. AB - OBJECTIVE: To observe the ethyl carbamate concentrations in different commercial fermented foods in Hangzhou in 2010. METHODS: In 2010, 237 commercial fermented food samples of eight categories, including yellow wine, white spirit, wine, beer, cooking wine, sauce, vinegar and fermented bean curd, were purchased from 3 different size markets respectively in Hangzhou. The ethyl carbamate was measured by gas chromatography-mass spectrometry in selection ion mode, after the samples were coupled with D5-ethyl carbamate, and purified by diatomite solid phase extraction column. RESULTS: The results showed that ethyl carbamate was detected in all samples analyzed (100%) with the range from 2.0 ug/kg to 515.0 ug/kg. The ethyl carbamate average (median) levels in 8 food categories were descending with fermented red bean curd (182.2 ug/kg (161.2 ug/kg)), yellow wine (159.6 ug/kg (121.0 ug/kg)), cooking wine (86.8 ug/kg (95.6 ug/kg)), white spirit (72.0 ug/kg (60.5 ug/kg)), soy sauce (47.2 ug/kg (40.7ug/kg)), vinegar (26.7 ug/kg (31.8 ug/kg)), wine (15.7 ug/kg (16.8 ug/kg)) and beer (2.2 ug/kg (2.3 ug/kg)). CONCLUSION: The ethyl carbamate was detected in all fermented foods in Hangzhou in 2010, and the levels of ethyl carbamate in red bean curd and yellow wine were higher than others. PMID- 22041565 TI - [Study on the mutations within the whole genome of influenza virus subtype A/H3N2 strains circulated in Zhejiang province from 1998 to 2009]. AB - OBJECTIVE: To analyze the consistency of evolution condition between HA gene and the whole genome of influenza virus subtype A/H3N2 strains isolated in Zhejiang province from 1998 to 2009, and to study the potential antigenic region on the whole genome. METHODS: The sequences of whole genome of 19 Zhejiang influenza virus isolates circulated from 1998 to 2009, which conserved by influenza laboratory of Zhejiang Provincial Centre for Disease Prevention and Control, were amplified using RT-PCR assays. The obtained sequences were used to conduct phylogenetic analysis with 10 contemporaneous vaccine strains. Three methods, including comparison of the amino acid substitutions, calculation of the entropy value and the filtering of positive selection sites, were used to confirm the mutable sites on each gene. RESULTS: The whole genome of influenza virus subtype A/H3N2 was 4466 amino acids in length, with 137 stable mutations. The 144, 158 aa of HA gene mutate four and three times respectively; 93, 143, 307, 370, 372 aa of NA gene and 450 aa of NP gene mutate twice, and there were 29% (12/41) and 77% (24/31) mutations of HA and NA genes occurred on the non-epitope regions respectively. Analysis of the entropy value suggest that many amino acid sites on the non-epitope regions were prone to mutation, including 3, 225, 361 aa of HA gene; 93, 143, 147, 150, 372 aa of NA gene; 113, 576, 586 aa of PB1 gene; 101,256, 382, 421, 437 aa of PA; 377, 450 aa of NP gene; 218 aa of M1 gene and 31 aa of M2 gene. CONCLUSION: Based on the whole genome of influenza virus subtype A/H3N2 strains isolated in Zhejiang province in 1998 to 2009, there may be several unknown or new antigen sites existing on the non-epitope regions of HA and NA genes and parts of internal genes. The phylogenetic tree constructed based on the complete sequence was more comprehensive than on the HA gene to reflect the genetic relationship and law of evolution among the influenza virus strains. PMID- 22041566 TI - [The prevalence of HIV-1 drug resistance and associated factors in AIDS patients receiving HAART in Zhecheng county, Henan province]. AB - OBJECTIVE: To understand the prevalence of HIV-1 drug resistance and its main factors in AIDS patients receiving to HAART in Zhecheng county, Henan province. METHODS: By cross-sectional survey, 378 AIDS patients who had received the national free antiretroviral therapy from July 2003 to March 2009 in Zhecheng county of Henan were selected. All recruits were interviewed and blood samples were collected. HIV-1 viral loads were measured by real-time polymerase chain reaction, HIV genotypic resistance was determined by an in-house polymerase chain reaction to amplify the HIV-1 pol gene region. RESULTS: Among 378 subjects receiving antiretroviral therapy, the prevalence of successful viral suppression was 42.9% (162/378), and HIV-1 drug resistance was detected in 47.1% (178/378) patients. The rate of resistance-associated mutations to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) was 46.6% (176/378), 37.8% (143/378) and 1.9% (7/378), respectively. Multivariate logistic regression analysis showed that the main risk factors associated with the prevalence of drug resistance included drug non-adherence (ratio of on-time drug intake in the past month < 90%:>= 90% = 64.5% (40/62):43.7% (138/316), OR = 2.3, 95%CI: 1.3 - 4.1), and initiation of anti-retroviral therapy (ART) with didanosine (DDI) (ART with DDI:ART with lamivudine (3TC) = 53.3% (137/257):33.9% (41/121), OR = 2.3, 95%CI = 1.1 - 4.5). CONCLUSION: The prevalence of HIV-1 drug resistance among ART patients in Zhecheng county of Henan was high. Drug non-adherence and initiation of ART with DDI were the main factors of drug resistance. PMID- 22041567 TI - [The etiological identification of an aseptic encephalitis outbreak (ten cases) in a hospital of Xiamen city, 2011]. AB - OBJECTIVE: To identify the etiology of an aseptic encephalitis outbreak (ten cases) in a hospital of Xiamen city from 11 to 17 May, 2011. METHODS: A total of ten patients' throat swabs, anal swabs and cerebrospinal fluid were collected and detected by RT-PCR for pan-enterovirus. The samples containing detectable pan enterovirus were tested by PCR with genotype-specific general primers located in VP1 region of enterovirus genotype A, B and C (HEV-A, B and C). The PCR products of VP1 segment were purified and sequenced, and phylogenetic analysis was performed. Meanwhile, the pathogens in those samples were isolated in Vero cell culture. Homologous analysis of VP1 sequences were carried out for the cultured virus samples and the original clinical samples to identify the outbreak etiology. RESULTS: Among the ten cases, seven cases were positive for pan enterovirus nucleic acid. When tested by genotype-specific PCR, the throat and anal swab samples from those 7 patients were positive with HEV-B VP1 primers. Meanwhile, the HEV-B VP1 segments were sequenced and phylogenetic analyzed, which indicated the seven cases were all infected by enterovirus Echo 30. The sequences from those samples had homology of 95.3% - 97.1% with the epidemic strains in Zhejiang, 2004. Out of the seven cases, the sequences of XM2, XM3, XM4, XM8 throat swab samples and XM3, XM6 throat samples showed 99.4% - 100.0% homology which were different from the sequence of XM1, and the homology was 92.8% - 93.4%. Furthermore, the viruses were isolated using Vero cells from XM1, XM2, XM3, XM4 and XM8 throat swab samples, and the VP1 sequence showed more than 99.9% homology with the original specimens. CONCLUSION: The local outbreak of aseptic encephalitis was caused by Echo 30 of enterovirus genotype B, and the epidemic strains may have different genetic background. PMID- 22041568 TI - [The cytotoxic effect and injury mechanism of deoxynivalenol on articular chondrocytes in human embryo]. AB - OBJECTIVE: This study was to explore the cytotoxic effect and the related injury mechanism of deoxynivalenol (DON) on articular chondrocytes in human embryo. METHODS: Articular cartilage cells were isolated from knees of human embryo and cultured in DMEM/F12 medium. The cells of the 4th generation were divided into five groups and incubated with varying concentrations of DON as the followings: control group and group with DON of 0.1, 0.2, 0.4, 1.0 ug/ml. The effects of DON were observed 72 hours after incubation. Cell apoptosis was assayed by flow cytometry (FCM) with Annexin V-FITC/PI staining; MMP-13 and PGE2 were detected by ELISA kits; NO was measured by Griess assay with spectrophotometer. Inducible nitric oxide synthase (iNOS) and collagen II in cells were detected by FCM. The expression levels of iNOS, mRNA and collagen II mRNA were measured with RT-PCR. RESULTS: The rates of cell apoptosis in DON groups were 6.78% - 19.05%, which were significantly higher than that in control (1.20%, F = 174.761, P < 0.05). The levels of NO in DON groups were 20.8 - 40.7 umol/L, which were significantly higher than that in control (10.2 umol/L, F = 91.966, P < 0.05). The levels of MMP-13 in DON groups were 0.25 - 0.56 umol/L, which were significantly higher than that in control (0 umol/L, F = 78.420, P < 0.05). The levels of PGE2 in DON groups were 3.2-20.6 umol/L, which were significantly higher than that in control (11.6 umol/L, F = 276.453, P < 0.05). The proportions of cells with positive iNOS in DON groups were 14.8% - 56.8% which were significantly higher than that in controls (7.1%, F = 214.614, P < 0.05). The proportions of cells with positive collagen II in groups with DON of 0.4 ug/ml and 1.0 ug/ml were 56.7% and 52.7%, which were significantly lower than that in control (62.2%, F = 5.134, P < 0.05). The relative absorbance values of iNOS mRNA in DON groups were 1.07 - 1.33, which were significantly higher than that in control (0.62, F = 8.358, P < 0.05). The levels of collagen II mRNA in groups with DON of 0.4 ug/ml and 1.0 ug/ml were 0.83 and 0.82, which were significantly lower than that in control (1.14, F = 7.887, P < 0.05). CONCLUSION: DON could promote anabolism of NO in articular cartilage cells by which up-regulated the expression of PGE2 and MMP-13, which both promoted resolution of articular cartilage matrix such as collagen II. DON induced apoptosis in articular cartilage cells. PMID- 22041569 TI - [The effect of birth weight and early growth on body fat composition and insulin sensitivity]. AB - OBJECTIVE: To investigate the effect of birth weight and early growth on body fat composition and insulin sensitivity. METHODS: The birth and growth data of 258 children of 6 to 7 years old in Guangzhou were collected from Jun.2009 to Feb. 2010. Physical and laboratory examination were preformed, which included body weight, body height and body fat composition index (body mass index (BMI), percentage of body fat (PBF), waist circumference to height ratio (WtHR), etc). Fasting blood glucose and insulin were measured. The homeostasis model assessment model for insulin resistance index (HOMA-IR) was calculated. According to birth weight, the children were divided into three groups from light to heavy: BW-I, BW II, BW-III group. Then according to change in weight SDS between 0 and 36 months, the children were divided into three groups: changers up (CU), non-changers (NC), changers down (CD) group. The effect of birth weight and early growth on body fat composition and insulin sensitivity were analyzed. RESULTS: Change in weight SDS between 0 and 36 months was higher in BW-I group (1.06 +/- 1.29) than in the BW II group (-0.19 +/- 0.94) and BW-III group (-0.10 +/- 1.20) (all P values < 0.01). Birth weight of the CU group ((2.90 +/- 0.47) kg) was lower than that of the NC group ((3.22 +/- 0.34) kg) and the CD group ((3.57 +/- 0.37) kg) (all P values < 0.01). The body fat composition index of BMI, PBF and WtHR were higher in the BW-III group ((16.35 +/- 2.13) kg/m(2), (17.03 +/- 5.88)%, (0.479 +/- 0.033)) than in the BW-I group ((15.46 +/- 2.06) kg/m(2), (14.06 +/- 5.25)%, (0.459 +/- 0.032)) and BW-II group ((15.47 +/- 1.58) kg/m(2), (14.09 +/- 5.01)%, (0.460 +/- 0.025)) (P < 0.01), while there was no significant difference between the BW-I group and the BW-II group (P > 0.05). The body fat composition index of BMI, PBF and WtHR were higher in the CU group ((16.44 +/- 2.20) kg/m(2), (16.51 +/- 5.78)%, (0.473 +/- 0.034)) than in the NC group ((15.62 +/- 1.74) kg/m(2), (14.49 +/- 5.30)%, (0.463 +/- 0.030)) and the CD group ((15.26 +/- 1.85) kg/m(2), (14.24 +/- 5.54)%, (0.462 +/- 0.031)) (all P values < 0.05). In the CU group, BMI, PBF and WtHR were higher in the BW-III-CU group ((18.76 +/- 2.56) kg/m(2), (22.19 +/- 8.28)%, (0.512 +/- 0.029)) than in the BW-I-CU group ((16.04 +/- 2.14) kg/m(2), (15.54 +/- 5.28)%, (0.467 +/- 0.034)) and BW-II-CU group ((16.70 +/- 1.36) kg/m(2), (17.12 +/- 4.44)%, (0.474 +/- 0.017)) (all P values < 0.05), while there was no significant difference between the BW-I-CU group and the BW-II-CU group (P > 0.05). HOMA-IR was higher in the CU group (1.27 +/- 0.44) than in the NC group (1.08 +/- 0.31) and the CD group (1.00 +/- 0.36) (all P values < 0.01). In the CU group, HOMA-IR was higher in the BW-III-CU group (1.69 +/- 0.48) than in the BW-I-CU group (1.21 +/- 0.41) and the BW-II-CU group (1.27 +/- 0.44) (all P values < 0.01), while there was no significant difference between the BW-I-CU and BW-II-CU group (P > 0.05). CONCLUSION: According to birth weight tertile, both lower birth weight individuals with more weight change-up growth postnatal early and higher birth weight individuals had greater body fat composition in childhood. They were high-risk people of insulin resistance. PMID- 22041570 TI - [The relationship between occupational stress and metabolic syndrome among policemen]. AB - OBJECTIVE: To explore the occupational stress factors associated with the prevalence of metabolic syndrome (MS) among male policemen. METHODS: Using cluster sampling method, we selected four Public Security Bureau within the jurisdiction of the station now in some city. All the male police were included as research objects, and finally 1490 persons were selected, health and occupational stress inventory-revised (OSI-R) questionnaire were used for epidemiological surveys, and anthropometric examination and chemical indicators were also measured at the same time. The analysis methods were chi-square test and unconditional logistical regression. RESULTS: Among the 1490 of research objects, 1483 completed the questionnaire, and 1480 of the eligible questionnaires were available.237 cases were MS, and the prevalence rate was 16.0%(237/1480). The number of cases who were high, moderate and lack of occupational stress in MS group were 8, 39 and 23, that in non-MS were 14, 114 and 131, respectively. The odds of occupational stress with the highest and medium among policemen than who were lack were 4.82 (95%CI: 1.50 - 15.41) and 3.33 (95%CI: 1.62 - 6.79); the average score of role ambiguity, role insufficiency and responsibility in the group of MS were (38.76 +/- 6.83), (25.74 +/- 7.22), (25.76 +/- 6.27); and that in non-MS were (37.55 +/- 6.85), (24.50 +/- 6.58), (25.05 +/- 5.95). The logistical regression analysis showed that: the likely three occupational risk stress factors which influencing the prevalence of MS were role ambiguity, role insufficiency and responsibility, and the OR (95%CI) were 1.06 (1.02 - 1.10), 1.04 (1.02 - 1.07) and 1.03 (1.01 - 1.06), respectively. CONCLUSION: Role ambiguity, role insufficiency and responsibility were the occupational risk stress factors associated with the prevalence of MS among male policemen. PMID- 22041571 TI - [Effect of early vitamin D supplementation on lung inflammatory factors in baby rat with asthma]. AB - OBJECTIVE: To explore the effect of different doses of 1,25-(OH)(2)VitD(3) early supplementation on airway inflammation and lung inflammatory factors in baby rats with asthma. METHODS: Forty male weaned Wistar rats were divided into normal group, model group, low 1,25-(OH)(2)VitD(3) group, middle 1,25-(OH)(2)VitD(3) group, high 1,25-(OH)(2)VitD(3) group using random number table (8 rats each group). The rats in low, middle and high 1,25-(OH)(2)VitD(3) groups were given 1, 4, 10 ug/kg of 1,25-(OH)(2)VitD(3) every other day by intraperitoneal injection respectively for 25 days. Except normal group, the rats in other groups were challenged with ovalbumin to establish the asthma model. The pathologic changes of lung tissue, the total white blood cell and classified cell counts in bronchoalveolar lavage fluid (BALF) were measured. The concentrations of IL-4, IL 5 and IFN-gamma in serum and BALF were measured by ELISA method. RESULTS: The level of total white blood cell counts in BALF were (5.98 +/- 1.67)*10(5)/ml, (25.34 +/- 4.28)*10(5)/ml, (17.24 +/- 3.3)*10(5)/ml, (9.31 +/- 3.37)*10(5)/ml, (45.1 +/- 15.75)*10(5)/ml, respectively (F = 33.453, P < 0.01). The percent ratio of EOS in BALF were (1.44 +/- 0.78)%, (17.81 +/- 6.88)%, (15.00 +/- 5.70)%, (8.89 +/- 3.66)%, (25.88 +/- 5.57)%, respectively (F = 27.299, P < 0.01). The level of IL-4 in serum of normal, model, low, middle and high-1,25-(OH)(2)VitD(3) groups were (0.62 +/- 0.54), (7.57 +/- 1.04), (3.58 +/- 0.56), (2.70 +/- 0.78) and (5.27 +/- 0.30) pg/ml, respectively (F = 116.287, P < 0.01); IL-5 in resume were (32.20 +/- 4.23), (67.14 +/- 18.14), (37.51 +/- 0.47), (40.69 +/- 2.47) and (124.60 +/- 36.19) pg/ml, respectively (F = 23.902, P < 0.01); IFN-gamma in serum were (79.71 +/- 10.08), (49.06 +/- 4.46), (59.15 +/- 2.51), (59.27 +/- 2.33) and (53.85 +/- 1.97) pg/ml, respectively (F = 39.954, P < 0.01). Also in BLAF, the IL-4 of all groups were (0.51 +/- 0.30), (102.92 +/- 54.61), (8.64 +/- 4.07), (3.10 +/- 1.28) and (33.67 +/- 8.1) pg/ml, respectively (F = 24.062, P < 0.01); the IFN-gamma were (247.37 +/- 189.18), (43.82 +/- 13.76), (81.32 +/- 17.07), (86.50 +/- 14.26) and (59.89 +/- 34.17) pg/ml, respectively (F = 7.157, P < 0.01); the IL-5 in BALF were (38.81 +/- 0.60), (80.48 +/- 17.90), (45.11 +/- 1.33), (43.39 +/- 1.11) and (149.60 +/- 45.87) pg/ml, respectively (F = 35.978, P < 0.01). Pathologic changes in lung of asthma rat groups were obvious. The lung pathologic changes in low and middle dose groups showed a significant improvement compared to the asthma group and high dosage group showed more serious pathologic changes compared to the low and middle dose groups. CONCLUSION: Intervention with appropriate dose of 1,25 (OH)(2)VitD(3) in the early life could improve lung pathologic changes and reduce the effect of inflammatory factors in air way of baby rat asthma model. However, overdose might play detrimental effect. PMID- 22041572 TI - [Translation and adjustment into Spanish language of the screening tool for mild cognitive impairment]. AB - BACKGROUND AND OBJECTIVES: The Test Your Memory (TYM) scale is a screening tool, which assesses mild cognitive impairment (MCI). It has shown better psychometric outcomes than the Mini-Mental State Examination (MMSE). We aimed to translate and adjust into Spanish a conceptually equivalent version. SUBJECTS AND METHOD: Translation-back translation method, complemented with qualitative methods, and pilot survey with 42 healthy Spanish people from different group of age to ensure the right comprehension. RESULTS: While translating, 54% of the items presented no difficulty at all; 27%, medium difficulty; 18% high difficulty. Some adaptations were made for cultural, grammatical and conceptual reasons. The pilot survey showed a good comprehension of the test. CONCLUSIONS: The TYM test could be a good choice for detecting MCI in the Spanish population and could resolve the problems caused by the limitations of the MMSE. PMID- 22041573 TI - Knee osteochondral fractures in skeletally immature patients: French multicenter study. AB - INTRODUCTION: Femoral or patellar osteochondral fractures complicating patellar dislocation are more frequently observed in adolescents than in adults. These incidental lesions of vulnerable joint cartilage are often neglected in the initial phase, which is regrettable given their good capacity for healing after repositioning. The objective of this study was to investigate the characteristics and analyze the results of repositioning these fractures in skeletally immature patients. MATERIAL AND METHODS: This retrospective multicenter study grouped 14 patients and knees (seven females). The mean age at the time of the accident was 12.9 years (range, 11.2-14.9 years) for the girls and 14 years (range, 12.2-15 years) for the boys. These fractures involved the lateral condyle in nine cases and the patella in five cases. The injury mechanism was secondary to demonstrated patellar dislocation (n=9) or a direct impact (n=4). In nine cases out of 14, a leisure sports accident was the cause. The injury was treated a mean 5.2 days (range, 0-20 days) after the accident. All of the detached fragments were repositioned surgically with screw fixation (n=5), resorbable pins (n=5), or pull out suture (n=4). Biological glue was added for six patients. Patellar stabilization was associated during the same procedure in two cases. RESULTS: No postoperative complications were observed. The results at the mean follow-up of 30 months (range, 15-89 months) showed no revision for failure, with all of the fractures demonstrating union at the final examination. The mean IKDC 2000 subjective score was 88+/-6 (range, 79-98) out of 100 points. The subjective satisfaction level was very satisfied in two cases and satisfied in the 12 others. The final IKDC score was A for eight patients, B for five patients, and C for one patient. Three patients underwent secondary patellar stabilization surgery. CONCLUSION: Better knowledge of this fracture and attentive reading of the radiographic images of a knee with hemarthrosis should result in more frequent diagnosis of this condition and adapted treatment. Unexplained hemarthrosis in a context of trochlear dysplasia should be considered to be associated with an OCF until proof of the contrary. A fragment released in a weightbearing zone should ideally be repositioned within 10 days but remains possible at 2 months. It regularly provides bone union and good results in children. PMID- 22041574 TI - Damage control orthopaedics in the context of battlefield injuries: the use of temporary external fixation on combat trauma soldiers. AB - INTRODUCTION: The purpose of this study was to analyze the use of temporary external fixation within the perspective of a damage control orthopedics attitude in the management of battlefield extremity injuries. HYPOTHESIS: Damage control orthopaedics (DCO) is a valuable treatment option for easy and rapid limb fracture stabilization in an unfavorable surgical environment. METHODS: Sixteen French soldiers wounded on the battlefield between 2004 and 2009 and managed by damage control orthopedics were included in this retrospective series. All patients were males with a mean age of 30 years (20-53 years). Eighteen external fixators were applied on the theater of operations for multiple injuries (five cases), closed fractures of the pelvis or long bones (three cases) and open osteoarticular lesions (ten cases). RESULTS: After medical evacuation from original theater, conversion to internal fixation was possible in five cases. External fixation was maintained in thirteen cases due to the severity of the lesions or infectious complications. Bone union was achieved in all cases. The mean time for bone union was 2.8 months (2 to 3 months) in case of conversion to internal fixation, and 6.3 months (1.5 to 17 months) when external fixation was extended. To achieve bone union, three devices were removed after a three or four month period and converted to rigid internal fixation associated with bone grafting. No case of septic complication was observed after early conversion. The only case of post-conversion infection occurred after three months of external fixation. After a mean follow-up of 19 months (6 to 49 months) all patients recovered functional autonomy and thirteen could return to duty. CONCLUSION: When possible, early conversion from external to internal fixation improves bone union and functional recovery after war limb injuries in properly selected patients. PMID- 22041575 TI - Extension of life span of Drosophila melanogaster by the inhibitors of tryptophan kynurenine metabolism. AB - Upregulation of kynurenine (KYN) formation from tryptophan (TRY) was associated with aging in animal and human studies. TRY - KYN metabolism is affected by the activities of TRY 2,3-dioxygenase 2 (TDO) and ATP-binding cassette (ABC) transporter regulating TRY access to intracellular TDO. We studied the effects of TDO inhibitor, alpha-methyl tryptophan (aMT), and ABC transported inhibitor, 5 methyl tryptophan (5MT), on the life span of wild strain female Drosophila flies (Oregon-R). aMT and 5MT prolonged mean and maximum life span (by 27% and 43%, and 21% and 23%, resp.). The present results are the first observation of the extension of life span of Drosophila melanogaster by inhibitors of TRY - KYN metabolism, and in line with literature and previous studies on prolonged life span of TDO- and ABC-deficient female Drosophila mutants. Inhibition of TDO and ABC transporter activity might offer the new target for anti-aging and anti-AAMPD interventions. PMID- 22041576 TI - Genetic characterization of ebi reveals its critical role in Drosophila wing growth. AB - The ebi gene of Drosophila melanogaster has been implicated in diverse signalling pathways, cellular functions and developmental processes. However, a thorough genetic analysis of this gene has been lacking and the true extent of its biological roles is unclear. Here, we characterize eleven ebi mutations and find that ebi has a novel role in promoting growth of the wing imaginal disc: viable combinations of mutant alleles give rise to adults with small wings. Wing discs with reduced EBI levels are correspondingly small and exhibit down-regulation of Notch target genes. Furthermore, we show that EBI colocalizes on polytene chromosomes with Smrter (SMR), a transcriptional corepressor, and Suppressor of Hairless (SU(H)), the primary transcription factor involved in Notch signalling. Interestingly, the mammalian orthologs of ebi, transducin beta-like 1 (TBL1) and TBL-related 1 (TBLR1), function as corepressor/coactivator exchange factors and are required for transcriptional activation of Notch target genes. We hypothesize that EBI acts to activate (de-repress) transcription of Notch target genes important for Drosophila wing growth by functioning as a corepressor/coactivator exchange factor for SU(H). PMID- 22041577 TI - Scratching for food: an original feeding behavior in an African flower breeding Drosophila. AB - Drosophila suma is a flower breeding species widespread in the Afrotropical region. We describe an original and so far unique feeding behavior in that species. Strong black spines on the fore tarsus of both sexes are used for scratching the surface of the petals: the juice pouring out from the scratched cells is immediately ingested and this might be the only source of food. D. suma has been investigated on two kinds of flowers, Ipomoea and Crinum. In spite of the very different shape and color of these flowers, the feeding behavior of the flies is the same. Various morphological and anatomical adaptations are described, especially those related to laying a few very big eggs. The taxonomic position of D. suma has long remained and still is elusive. Further taxonomic and phylogenetic investigations would thus be needed to understand how adaptation to flower breeding has evolved. PMID- 22041578 TI - Systemic lupus erythematosus one disease or many? AB - Systemic lupus erythematosus (SLE) characterizes by a variety of clinical manifestations and the presence of a wide profile of autoantibodies. This clinical and serological heterogeneity raised the question: is SLE a single disease with varied phenotypes, or a similar phenotype shared by different diseases with diverse pathogenic mechanisms? Herein we debate the clinical, genetic, hormonal and serological differences typically observed in SLE on the one hand, and the numerous similarities between subtypes of this disease on the other. Leading to the conclusion that SLE may be considered not as a single disease but rather as a single syndrome, which defines by a set of signs, symptoms, or phenomena that occur together and suggest a particular abnormality. Additionally, the accumulated knowledge on gene expression pathways, autoantibodies clusters, hormonal and environmental factors associated with SLE may allow a better classification of this syndrome and updating of SLE criteria. This may further allow targeted biologics and other therapies as well as "personalized medicine" to begin. PMID- 22041579 TI - Autoantibodies in lupus: culprits or passive bystanders? AB - Several autoantibodies are culprits in the pathogenesis of organ damage in systemic lupus erythematosus, by means of established or postulated mechanisms, whereby inducing a perturbation of cell structure and function, with consequent tissue-organ impairment. Common autoantibody-mediated mechanisms of damage include cell surface binding with or without cytolysis, immune complex-mediated damage, penetration into living cells, binding to cross-reactive extracellular molecules. Experimental data from both murine models and humans have recently clarified the key role of autoantibodies in severe organ involvements, including nephritis, neuropsychiatric (NP) dysfunction, and cerebrovascular disease (CVD). In lupus nephritis early and late phases are distinguishable and mediated by different processes in which anti-chromatin antibodies are both inducing and perpetuating agents, by immune-complex formation and massive deposition in mesangial matrix at first, and in glomerular basement membrane at end-stage. Also NP abnormalities occur very early, much earlier than other systemic manifestations, and exacerbate with the increase in autoantibody titers. Among the autoantibodies mainly implicated in neurolupus, anti-beta2 glycoprotein I (beta2GPI) antibodies are preferentially involved in focal NP events which are a consequence of non-inflammatory microangiopathy; otherwise, anti-ribosomal P protein antibodies and N-methyl-d-aspartate receptor (NMDAR) antibodies cause diffuse NP events through a direct cytotoxic effect on neuronal cells at specific brain zones. PMID- 22041580 TI - Genes, epigenetic regulation and environmental factors: which is the most relevant in developing autoimmune diseases? AB - Autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and inflammatory bowel disease, have complex pathogeneses and likely multifactorial etiologies. The current paradigm for understanding their development is that the disease is triggered in genetically-susceptible individuals by exposure to environmental factors. Some of these environmental factors have been specifically identified, while others are hypothesized and not yet proven, and it is likely that most have yet to be identified. One interesting hypothesis is that environmental effects on immune responses could be mediated by changes in epigenetic regulation. Major mechanisms of epigenetic gene regulation include DNA methylation and histone modification. In these cases, gene expression is modified without involving changes in DNA sequence. Epigenetics is a new and interesting research field in autoimmune diseases. We review the roles of genetic factors, epigenetic regulation and the most studied environmental risk factors such as cigarette smoke, crystalline silica, Epstein-Barr virus, and reproductive hormones in the pathogenesis of autoimmune disease. PMID- 22041581 TI - The role of liver transplantation for intrahepatic cholangiocarcinoma: a single center experience. AB - BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (ICC) is not a widely accepted indication for liver transplantation (LT). The present study describes our institutional experience with patients who underwent transplantation for ICC. METHODS: A retrospective analysis was performed on 11 consecutive patients with ICC who underwent LT between October 2003 and November 2008 at our institution. RESULTS: At a median patient follow-up interval of 10 months (2-56), the median survival time was 9 months (2.5-53). The perioperative mortality and the recurrence rate were 0 and 45.5%, respectively. Five patients are currently alive 10, 12, 41, 51 and 53 months after LT, respectively. One patient died 3 months after LT as a result of bile leak and toxic shock, and 5 patients died of tumor recurrences at 2.5, 8, 8, 9 and 10 months post-LT, respectively. The 1-, 2-, 3- and 4-year disease-free survival rates and overall survival rates of all the patients were 51.9, 51.9, 51.9 and 51.9%, and 50.5, 50.5, 50.5 and 50.5%, respectively. CONCLUSION: With better and strict patient selection, the prognosis of LT for ICC could be improved. ICC patients with lymph node involvement, vascular or bile duct invasion are contraindicated for LT. PMID- 22041582 TI - Kinetic and in silico analysis of the slow-binding inhibition of human poly(A) specific ribonuclease (PARN) by novel nucleoside analogues. AB - Poly(A)-specific ribonuclease (PARN) is a 3'-exoribonuclease that efficiently degrades poly(A) tails and regulates, in part, mRNA turnover rates. We have previously reported that adenosine- and cytosine-based glucopyranosyl nucleoside analogues with adequate tumour-inhibitory effect could effectively inhibit PARN. In the present study we dissect the mechanism of a more drastic inhibition of PARN by novel glucopyranosyl analogues bearing uracil, 5-fluorouracil or thymine as the base moiety. Kinetic analysis showed that three of the compounds are competitive inhibitors of PARN with K(i) values in the low MUM concentration and significantly lower (11- to 33-fold) compared to our previous studies. Detailed kinetic analysis of the most effective inhibitor, the uracil-based nucleoside analogue (named U1), revealed slow-binding behaviour. Subsequent molecular docking experiments showed that all the compounds which inhibited PARN can efficiently bind into the active site of the enzyme through specific interactions. The present study dissects the inhibitory mechanism of this novel uracil-based compound, which prolongs its inhibitory effect through a slow binding and slow-release mode at the active site of PARN, thus contributing to a more efficient inhibition. Such analogues could be used as leading compounds for further rationale design and synthesis of efficient and specific therapeutic agents. Moreover, our data reinforce the notion that human PARN can be established as a novel molecular target of potential anti-cancer agents through lowering mRNA turnover rates. PMID- 22041583 TI - Exposure to cadmium chloride influences astrocyte-elevated gene-1 (AEG-1) expression in MDA-MB231 human breast cancer cells. AB - It is known that cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity and intracellular signalization in normal and pathological human cells. We have already shown that Cd exerts a cytotoxic effect on neoplastic MDA-MB231 cells from the human breast, which is characterized by the onset of a "non-classical" apoptotic kind of death, impairment of mitochondrial activity and drastic changes in gene expression pattern. In the present study, employing a combination of conventional and differential display-PCR techniques, immunocytochemical, ELISA and Western analyses, we extended the knowledge on the transcriptional modulation exerted by the metal demonstrating that in MDA-MB231 cells 5 MUM CdCl(2) treatment for 96 h selectively down-regulates astrocyte-elevated gene-1 (AEG-1) and reduces the accumulation of its protein product which appears to be associated with the internal cytomembranes and also present in the nucleoplasm. In addition, due to the acknowledged role of AEG-1 in the intranuclear shuttling of NF-kappaB p65 subunit, we also showed that CdCl(2) treatment determines the decrease of p65 amount in nuclear extracts and the down-regulation of the NF-kappaB downstream genes c-fos and c-jun, thus providing a new contribution to the comprehension of the intracellular molecular mechanisms implicated in Cd-breast cancer cell interactions. PMID- 22041585 TI - On the relationship between mouth opening and "broken mirror neurons" in autistic individuals. AB - Electromyographies of the mylohyoid muscle (MH) during the execution of the goal oriented action "grasping to eat" have been used to determine the time relationship between the opening of the mouth and the beginning of the movement. This has been used to distinguish the behaviour of typical developing (TD) children from that of highly functioning autistic (ASD) individuals. The results of previous studies appeared to provide evidence of a deficit in action chain organization in ASD subjects and prompted the hypothesis of a "broken" mirror neuron system (MNS) for these individuals. Our results show the MH activation timing is not reliable in discriminating between TD and ASD children and the distance between the food and the subject plays a key role on the MH activation timing and cannot be neglected when analysing these type of data. The preliminary investigation on the effects of external perturbations also shows that these might have an effect on the results and further investigations are warranted. It appears that there is not enough evidence to support a link between ASD and a broken mirror network system (MNS), and the experimental results must be carefully interpreted before developing therapeutic or rehabilitative protocols. PMID- 22041584 TI - Caveolin-1 promotes pancreatic cancer cell differentiation and restores membranous E-cadherin via suppression of the epithelial-mesenchymal transition. AB - Pancreatic cancer is one of the deadliest cancers due to early rapid metastasis and chemoresistance. Recently, epithelial to mesenchymal transition (EMT) was shown to play a key role in the pathogenesis of pancreatic cancer. To understand the role of caveolin-1 (Cav-1) in EMT, we over-expressed Cav-1 in a pancreatic cancer cell line, Panc 10.05, that does not normally express Cav-1. Here, we show that Cav-1 expression in pancreatic cancer cells induces an epithelial phenotype and promotes cell-cell contact, with increased expression of plasma membrane bound E-cadherin and beta-catenin. Mechanistically, Cav-1 induces Snail downregulation and decreased activation of AKT, MAPK and TGF-beta-Smad signaling pathways. In vitro, Cav-1 expression reduces cell migration and invasion, and attenuates doxorubicin-chemoresistance of pancreatic cancer cells. Importantly, in vivo studies revealed that Cav-1 expression greatly suppresses tumor formation in a xenograft model. Most interestingly, Panc/Cav-1 tumors displayed organized nests of differentiated cells that were totally absent in control tumors. Confirming our in vitro results, these nests of differentiated cells showed reexpression of E-cadherin and beta-catenin at the cell membrane. Thus, we provide evidence that Cav-1 functions as a crucial modulator of EMT and cell differentiation in pancreatic cancer. PMID- 22041586 TI - Multiplex detection of bacteria in complex clinical and environmental samples using oligonucleotide-coupled fluorescent microspheres. AB - Bacterial vaginosis (BV) is a recurring polymicrobial syndrome that is characterized by a change in the "normal" microbiota from Lactobacillus-dominated to a microbiota dominated by a number of bacterial species, including Gardnerella vaginalis, Atopobium vaginae, and others. This condition is associated with a range of negative health outcomes, including HIV acquisition, and it can be difficult to manage clinically. Furthermore, diagnosis of BV has relied on the use of Gram stains of vaginal swab smears that are scored on various numerical criteria. While this diagnostic is simple, inexpensive, and well suited to resource-limited settings, it can suffer from problems related to subjective interpretations and it does not give a detailed profile of the composition of the vaginal microbiota. Recent deep sequencing efforts have revealed a rich, diverse vaginal microbiota with clear differences between samples taken from individuals that are diagnosed with BV compared to those individuals that are considered normal, which has resulted in the identification of a number of potential targets for molecular diagnosis of BV. These studies have provided a wealth of useful information, but deep sequencing is not yet practical as a diagnostic method in a clinical setting. We have recently described a method for rapidly profiling the vaginal microbiota in a multiplex format using oligonucleotide-coupled fluorescent beads with detection on a Luminex platform. This method, like current Gram stain-based methods, is rapid and simple but adds the additional advantage of exploiting molecular knowledge arising from sequencing studies in probe design. This method therefore provides a way to profile the major microorganisms that are present in a vaginal swab that can be used to diagnose BV with high specificity and sensitivity compared to Gram stain while providing additional information on species presence and abundance in a semi-quantitative and rapid manner. This multiplex method is expandable well beyond the range of current quantitative PCR assays for particular organisms, which is currently limited to 5 or 6 different assays in a single sample. Importantly, the method is not limited to the detection of bacteria in vaginal swabs and can be easily adapted to rapidly profile nearly any microbial community of interest. For example, we have recently begun to apply this methodology to the development of diagnostic tools for use in wastewater treatment plants. PMID- 22041587 TI - Contamination risk of reusing daily disposable contact lenses. AB - PURPOSE: This study investigated contamination of saline and daily disposable contact lens (DDCL) stored overnight after use in the original blister pack and the practices of a group of DDCL users. METHODS: Twenty DDCL wearers placed their lenses after 1 day's use back into the blister pack saline (BPS) and left them overnight before transferring both lens and BPS to a new CL case. The lens and BPS were cultured the following day, and total number of organisms, Staphylococci, and gram negative organisms enumerated. Each subject submitted five pairs of lenses over a 1 month period. RESULTS: Ninety-five percent of subjects had at least one pair of contaminated lenses, and the BPS yielded similar results to the contaminated lenses, with staphylococcal contamination being predominant. Three subjects admitted to not washing their hands before handling their lenses and six to habitual reuse of their lenses with storage in the BPS. There was a higher risk of contamination in male subjects. CONCLUSIONS: Reuse of lenses poses an important risk for DDCL users because they are unlikely to have received proper training in cleaning and disinfection of lenses and do not use a lens case or disinfecting solutions. Overnight storage in BPS results in contaminated lenses which if reused increases the infection risk especially with Staphylococci. It is important that practitioners carefully educate their patients in correct use of DDCL and, as cost of lenses is a major factor in willingness to reuse, ensure that DDCL is the most suitable choice when prescribing. PMID- 22041588 TI - New bi-sign aspheric IOL and its application. AB - PURPOSE: To present a bi-sign aspheric intraocular lens (IOL) and make theoretical comparisons with spherical and one-sign aspheric IOLs for retinal image quality in mesopic conditions and intermediate image capability in photopic conditions. METHODS: Using ray-tracing in pseudophakic eye models, retinal image quality in terms of modulation transfer function was analyzed between the bi-sign aspheric and three types of one-sign aspheric IOLs and the spherical IOL for the range of corneal asphericities and different lens misalignments at 5 mm pupil diameter; comparison is made with the spherical IOL at defocus conditions characterized by negative refractive errors at 3 mm pupil diameter. RESULTS: Retinal image quality of the bi-sign aspheric lens was equal to or exceeded the one-sign aspheric and spherical IOLs in the majority of anterior cornea asphericities and lens misalignments within the spatial frequencies of 6 to 15 c/deg. Intermediate image capability of the bi-sign aspheric exceeded the spherical IOL. CONCLUSIONS: A new bi-sign aspheric lens produces regions of opposite spherical aberrations in the eye model with pupil diameters above 3 mm to balance out aberrations within the lens itself in addition to compensating corneal aberration as with a one-sign aspheric lens. This allows reduction in the variability of the retinal image quality at different anterior cornea asphericities and lens misalignments, when compared with a one-sign aspheric and spherical lens. The bi-sign aspheric produces positive longitudinal spherical aberration in the eye model within 3 mm pupil diameter that improves intermediate image capability when compared with the spherical IOL. PMID- 22041589 TI - Effect of phospholipid deposits on adhesion of bacteria to contact lenses. AB - PURPOSE: Protein and lipid deposits on contact lenses may contribute to clinical complications. This study examined the effect of phospholipids on the adhesion of bacteria to contact lenses. METHODS: Worn balafilcon A (n = 11) and senofilcon A (n = 11) were collected after daily wear and phospholipids were extracted in chloroform:methanol. The amount of phospholipid was measured by electrospray ionization mass spectrometry. Unworn lenses soaked in phospholipids were exposed to Pseudomonas aeruginosa and Staphylococcus aureus. After 18 h incubation, the numbers of P. aeruginosa or S. aureus that adhered to the lenses were measured. Phospholipid was tested for possible effects on bacterial growth. RESULTS: A broad range of sphingomyelins (SM) and phosphatidylcholines (PC) were detected from both types of worn lenses. SM (16:0) (m/z 703) and PC (34:2) (m/z 758) were the major phospholipids detected in the lens extracts. Phospholipids did not alter the adhesion of any strain of P. aeruginosa or S. aureus (p > 0.05). Phospholipids (0.1 mg/mL) showed no effect on the growth of P. aeruginosa 6294 or S. aureus 031. CONCLUSIONS: Phospholipids adsorb/absorb to contact lenses during wear, however, the major types of phospholipids adsorbed to lenses do not alter bacterial adhesion or growth. PMID- 22041590 TI - Ametropias in school-age children in Fada N'Gourma (Burkina Faso, Africa). AB - PURPOSE: To assess epidemiological aspects of refractive errors in school-age children in Burkina Faso (west-central Africa). METHODS: A total of 315 school children (ranging from 6 to 16 years of age and belonging to different ethnic groups) taken at random from two urban schools in eastern Burkina Faso were examined to assess their refractive error, which was determined by non cycloplegic retinoscopy with optical fogging. The standard Refractive Error Study in Children (RESC) definitions of refractive errors were used: myopia <=-0.5 D spherical equivalent (SE) in at least one eye, hyperopia >=2 D SE in at least one eye, astigmatism <=-0.75 D cylinder in at least one eye, and anisometropia >=1 D SE difference between the two eyes. RESULTS: Unilateral myopia and bilateral myopia were found in 2.5 and 1%, respectively; unilateral hyperopia in 17.1%, bilateral hyperopia in 8.6%; astigmatism in at least one eye in 11.7%. The highest prevalence value (18.4%) of astigmatism (<=-0.75 D) in at least one eye was found in the Gourmantche ethnic group. The low prevalence of large refractive errors makes visual acuity in these children very good (visual acuity logarithm of the minimum angle of resolution -0.073 +/- 0.123 SD). CONCLUSIONS: There was a low prevalence of myopia in these African school children. Clinically significant high hyperopia (>=+2 D SE) was also uncommon. There were no significant differences between the distributions of refractive errors according to gender or ethnicity. With respect to age groups, the prevalences of hyperopia and astigmatism were significantly higher in the younger age groups. PMID- 22041591 TI - [How are the abstracts reviewed and submitted to the French Pediatric Society?]. PMID- 22041592 TI - [Multidisciplinary consultation at the home of children with cystic fibrosis: experience of a specialized center]. PMID- 22041593 TI - [Health care workers' knowledge and vaccination coverage against pertussis in a French pediatric and maternity ward]. PMID- 22041594 TI - [Prepubertal urethritis in boys]. PMID- 22041595 TI - [Interventional cardiac catheterization in children]. AB - With the technological progress, the role of the cardiac catheterization has dramatically changed, moving from diagnostic to therapeutic and becoming adjuvant to surgical procedures. In various congenital heart defects, it allows to postpone the need for surgery or even cancel the surgical indication being less invasive and as powerful as surgery. It is thanks to many technological advances, in particular with the development of devices with memory alloy, that the catheterization makes such great strides today, and the miniaturization of the prosthetic material makes it possible to push back more and more the limits of feasibility which remain related to the smallness of the vascular accesses at the newborn age. The future of this discipline lies in the hybrid procedures, where a true teamwork between the surgeons and the pediatric cardiologists makes it possible to bring the best therapeutic strategy for patients with congenital heart defects. PMID- 22041596 TI - [Turner Syndrome: what's new in medical care?]. AB - Turner syndrome is a rare genetic disorder, affecting approximately one in 2500 live-born female, due to total or partial absence of the X chromosome. Typical clinical features are short stature and premature ovarian failure and less constantly phenotypic particularities such as congenital malformations, acquired cardiovascular, otological (hearing impairment), autoimmune and metabolic pathologies. The phenotype is highly variable with slight or even normal phenotype. Several studies have shown that growth hormone treatment improves adult height. The possibility of pregnancies after oocyte donation highlights the high risk of these pregnancies requiring a careful follow-up, especially in terms of cardiovascular issues. Although the quality of life seems similar to the normal population, the presence of cardiovascular and otological diseases, and delayed feminisation are associated with an impaired quality of life. Early diagnosis and regular screening for potentials associated complications are essential in the medical follow-up of these patients. The recent publication of recommendations should lead to an optimization and harmonisation of the medical practices and follow-up from paediatric age to adulthood, a lowering morbidity and self-esteem improvement. The interest of ovarian cryopreservation at an early age in these patients is under investigation. PMID- 22041597 TI - [Streptococcal toxic shock syndrome or Kawasaki disease? Two case studies of children with group A streptococcal pneumonia empyema]. AB - We report 2 cases of children with group A streptococcus pyogenes pleuropneumonia, in one child associated with Kawasaki disease and in the other with streptococcal toxic shock syndrome. These 2 features, with theoretically well-defined clinical and biological criteria, are difficult to differentiate in clinical practice, however, likely due to their pathophysiological links. In case of clinical doubt, an echocardiography needs to be performed to search for coronary involvement and treatment including intravenous immunoglobulins, and an antibiotic with an anti-toxin effect such as clindamycin has to be started early. PMID- 22041598 TI - [Spinal muscular atrophy: frequent cause of congenital hypotonia in Morocco]. AB - INTRODUCTION: Congenital hypotonia is a non specific symptom frequently seen in newborns and infants, and whose etiological diagnosis is often difficult due to the lack of specialized and affordable explorations. Childhood-onset proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by degeneration of the anterior horn cells of the spinal cord, leading to progressive paralysis with muscular atrophy. In more than 95% of the cases, it results from deletion of exon 7 of the SMN gene localized on 5q13, easily identified by molecular biology. OBJECTIVE: To determine the prevalence of the deletion of exon 7 of the SMN gene in congenital hypotonia with an unknown cause in Morocco. PATIENTS AND METHODS: We investigated the deletion of exon 7 of the SMN gene in 87 newborns and infants with congenital hypotonia. The cause of congenital hypotonia could not be determined in 60 of them, while 27 had electrophysiological evidence for an involvement of the anterior horn cells. RESULTS: The homozygous deletion of the SMN gene was detected in 23 of the newborns with unknown cause for hypotonia (38%) and in 21 of the infants whose electromyogram suggested infantile spinal amyotrophy (78%). CONCLUSION: This study underlines the advantages of a systematic search for the deletion of exon 7 of the SMN gene in every infant suffering from congenital hypotonia due to an unknown cause, particularly when the child's vital prognosis is at stake. This genetic test, easily implemented, should be systematically proposed after an attentive clinical evaluation in countries where the etiological diagnosis of congenital hypotonia is not systematic. PMID- 22041599 TI - Cerebral aneurysmal childhood arteriopathy. PMID- 22041600 TI - Detection of chromogranin A in the adrenal gland extracts of different animal species by an enzyme-linked immunosorbent assay using Thomsen-Friedenreich antigen-specific Amaranthus caudatus lectin. AB - The reactivity of different lectins with crude chromogranin A (CgA) obtained from different animals, namely, cow, horse, dog, pig, and dolphin, was examined to identify lectin(s) that would be useful as coating reagent(s) in a sandwich enzyme-linked immunosorbent assay (ELISA). Of the different lectins studied, the Amaranthus caudatus lectin (ACA), which is specific for the Thomsen-Friedenreich (T)-antigen (Galbeta1-3GalNAc), was found to react with the CgA from different animals by western blotting. Purified rabbit anti-bovine CgA antibody was also found to cross-react with the crude CgA preparations. On the basis of these findings, a sandwich ELISA was developed with ACA as the coating reagent and anti bovine CgA antibody as the probing antibody. Using this method, concentration dependent curves ranging from 0.003 MUg/mL to 25 MUg/mL and from 0.02 MUg/mL to 25 MUg/mL were obtained for bovine CgA and canine CgA, respectively. Similarly, concentration-dependent curves were obtained for the equine, swine, and dolphin crude CgA extracts. Thus, ACA is concluded to be a valuable reagent for CgA detection in crude extracts from different animal species, and for CgA isolation/purification. PMID- 22041601 TI - A novel method to load topotecan into liposomes driven by a transmembrane NH4EDTA gradient. AB - Antitumor drugs not only cause cytocidal effect on cancer cells, but also damage on normal healthy tissues, resulting in side effects. Liposome encapsulation can result in reduced systematic distribution due to the enhanced permeability and retention (EPR) effect, accompanied by drug accumulation in liver, spleen, and other immune organs, which can cause damage to those organs. It has been demonstrated that EDTA, frequently used as a chelator, possesses a synergistic antitumor effect. Indeed, our previous study showed that EDTA could reduce the toxicity of anthracyclines to the heart and immune organs. In this study, we intended to encapsulate topotecan within liposome adopting transmembrane NH(4)EDTA gradient in order to increase the antitumor activity and decrease the toxicity against normal immune organs. Regarding the encapsulation efficiency of topotecan liposomes, both the pH value of the buffer and the cholesterol content showed significant effects on encapsulation and drug retention. Liposome encapsulation dramatically increased the antitumor activity of topotecan compared to free drug (p<0.05), while similar efficacy was obtained from liposomes prepared by a NH(4)EDTA gradient or a (NH(4))(2)SO(4) gradient (tumor inhibition ratios were 85.6% and 84.1%, respectively). However, a significant decrease in toxicity against the immune organs was found in liposomes prepared by a NH(4)EDTA gradient compared to those prepared by a (NH(4))(2)SO(4) gradient. These results suggest the superiority of the proposed gradient for topotecan encapsulation in decreasing its toxicity on immune systems. PMID- 22041602 TI - Bioavailability enhancement of zaleplon via proliposomes: Role of surface charge. AB - The present systematic study focused to investigate the combined advantage of proliposomes and surface charge for improved oral delivery of zaleplon. The zaleplon loaded proliposomes were prepared using hydrogenated soyphosphatidylcholine (HSPC) and cholesterol (CHOL) in varying ratios, and the optimized formulation was tailored with dicetyl phosphate and stearylamine to obtain negative and positive charged vesicles, respectively. The formulations were characterized for micromeritics, size, zeta potential, and entrapment efficiency. Further, in vitro release and dissolution study carried out provide an insight on the stability and enhanced dissolution of zaleplon from proliposome formulations. The solid state characterization (SEM, DSC, and PXRD) studies unravel the transformation of zaleplon to amorphous or molecular state from the native crystalline form. To depict the conclusions, in situ single-pass perfusion and bioavailability studies were carried out in rats. The significant increase in effective permeability coefficient (Peff) and rate and extent of absorption from cationic vesicles indicate the importance of surface charge for effective uptake across the gastrointestinal tract. Overall a two- to fivefold enhancement in bioavailability in comparison with control confers the potential of proliposomes as suitable carriers for improved oral delivery of zaleplon. PMID- 22041603 TI - Acute and general medicine on opposite sides of the world. PMID- 22041604 TI - Complications of emergency refeeding in anorexia nervosa: case series and review. AB - The refeeding syndrome is common among patients with anorexia nervosa. It may be lethal and has many manifestations. We report a case series of 14 anorexic patients admitted for feeding to a single British centre. There was a high prevalence of the refeeding syndrome, with three cases requiring higher dependency unit support and one death. We present a review of the refeeding syndrome in anorectics and highlight our impression that infection among such patients may be serious and under-recognised. PMID- 22041605 TI - Acute Angle Closure Glaucoma (AACG): an important differential diagnosis for acute severe headache. AB - Acute headache is a common presenting symptom in the acute medical unit. We present a case of Acute Angle Closure Glaucoma (AACG) presenting with acute severe headache. It highlights the importance of remembering this ophthalmologic emergency and reminds us of its clinical presentation. The rapid assessment and diagnosis of AACG allowed prompt treatment and likely prevented the patient from losing her vision. PMID- 22041606 TI - Isolated syncope - an uncommon presenting feature of pulmonary embolism. AB - We describe a case of a 62 year old man who presented with transient loss of consciousness following exertion. On presentation to hospital, he was haemodynamically stable and was not breathless, tachycardic or hypoxic at rest. The finding of exercise-induced desaturation on pulse oximetry triggered further investigations which confirmed the presence of PE. PMID- 22041607 TI - Mucositis, conjunctivitis but no rash - the "Atypical Stevens - Johnson syndrome". AB - The Stevens-Johnson syndrome (SJS) classically involves a rash, conjunctivitis and mucositis. We describe the case of a young adult male with isolated mucositis and conjunctivitis . Previous rare reports of severe SJS like syndromes without a rash are confined to children, usually with mycoplasma pnemoniae infection.(1) Terminology for this syndrome includes - "Stevens-Johnson Syndrome without skin lesions", or "Atypical Stevens - Johnson Syndrome".(2) This case highlights the importance of maintaining an open mind when a "full house" of clinical features is absent. It also illustrates the use of a rapid electronic literature review as a clinical tool. The importance of updating records when a drug has been cleared of causing harm is highlighted. PMID- 22041608 TI - Preventing deaths in ambulatory care from isolated pelvic vein deep vein thrombosis: Mortality and Mortality meetings have a key role. AB - Isolated Pelvic vein Deep Venous Thrombosis (DVT) is a relatively rare phenomenon, but is usually not identified by conventional lower limb duplex Ultrasound scanning. We present two cases of isolated iliac vein thrombosis; the first resulting in the patient's death from Pulmonary Embolism (PE) after normal lower limb duplex scan. The second case was identified and successfully treated after introduction of a revised investigation algorithm following the first case. The literature supports the use of magnetic resonance imaging, CT venography, or ascending venography, to diagnose this condition. PMID- 22041609 TI - The acute medicine - speciality interface: experience in a large teaching hospital. PMID- 22041610 TI - The acute medicine - speciality interface: experience in a district general hospital. PMID- 22041611 TI - Meeting the challenges of Acute Care Quality Indicators. AB - The Royal College of Physicians and Society of Acute Medicine have proposed the introduction of Acute Care Quality Indicators. These include the need for rapid initial patient assessment and instigation of a management plan.1 Reductions in junior doctor working hours may impact on our ability to meet these standards. We present the result of a service review of 297 consecutive admissions to a large acute medical unit. This has identified a marked dichotomy between waiting times during daytime and out-of-hours, despite appropriate response to initial triage. We conclude that further service redevelopment is required to reach the standards proposed in the current Acute Care Quality Indicators. PMID- 22041614 TI - Falls in older people - an overview for the acute physician. AB - Falls are common amongst older adults inflicting a substantial socioeconomic burden. Aetiology is often multifactorial. Comprehensive individualised assessment is pivotal to direct effective interventions. We provide an overview of falls and highlight an approach for acute physicians who will increasingly encounter this mode of presentation in an ageing population. PMID- 22041615 TI - The emergency management of the patient presenting with shock. PMID- 22041616 TI - Quality improvement and acute medicine. PMID- 22041617 TI - A traveller with haemoptysis. PMID- 22041618 TI - Hypokalaemia, drugs and the QT interval - a recipe for disaster. PMID- 22041619 TI - The clinician's responsibility in relation to DVLA guidance. PMID- 22041620 TI - Outpatient parenteral antibiotic therapy for cellulitis. PMID- 22041622 TI - Incidental detection of breast apocrine carcinoma via endometrial cytology. AB - Breast apocrine carcinoma is a rare malignancy characterized histologically by a predominance of acidophilic tumor cells exhibiting apocrine metaplasia. Apocrine tumors represent only about 0.4% of all breast cancers. Many cases are diagnosed at stage I or II; thus, the prognosis is better than that for other types of breast cancer. Here we present a 57-year-old female patient with primary apocrine breast carcinoma that was incidentally discovered by endometrial cytology. The patient had undergone routine uterine cancer screening at the age of 56 with resulting positive endometrial cytology. Subsequent histological examination of an endometrial biopsy revealed suspected metastatic uterine adenocarcinoma. Further evaluation revealed a 3-cm mass in the left breast, which was histopathologically diagnosed as breast cancer. Dual procedures were performed at the departments of gynecology and breast surgery. The patient underwent a modified radical mastectomy of the left breast and left axillary lymph node dissection. Laparotomy revealed multiple adhesions throughout the peritoneal cavity that suggested invasive metastatic cancer, and a right adnexectomy was performed. Histopathological examination of the resected left breast and right ovary tissues revealed apocrine carcinoma. Thus, stage IV breast cancer was diagnosed. The patient finished 6 cycles of paclitaxel and is now under observation on an outpatient basis. In this patient, breast cancer was discovered incidentally through a detailed work-up after a positive result of endometrial cytology. Uterine cancer screening has the potential, although rare, to detect metastatic cancer originating elsewhere. This should be taken into consideration during the work-up due to positive endometrial cytology. PMID- 22041623 TI - Evidence of mephedrone chronic abuse through hair analysis using GC/MS. AB - Mephedrone is a synthetic derivative of cathinone which is becoming more common on the recreational drug market. Several intoxications following mephedrone abuse have been reported though published papers have focused essentially on analytical approaches for biological fluids and only one has involved a hair sample. After the development and validation of a new method, the first series of positive results for mephedrone in hair specimens is reported here. After decontamination of the hair strand in methylene chloride, hair segments were cut into small pieces with scissors, weighed and incubated overnight in Soerensen buffer pH 7.0 in the presence of deuterated 3,4-methylenedioxymethamphetamine (MDMA) at 40 degrees C. The incubation medium was extracted using ethyl acetate after alkalinisation with 1N sodium hydroxide (NaOH). Before injection, the dry extract was derivatized using a mixture of heptafluorobutyric anhydride/ethyl acetate (100:50, v/v), evaporated and dissolved in ethyl acetate (25MUl). After introduction of 1MUl of the extract onto a splitless injector, chromatographic separation was achieved on a HP 6890 gas chromatograph equipped with a 5-MS capillary column. Detection was achieved in single ion monitoring mode (m/z 254 119-210 for mephedrone, m/z 258-213 for MDMA-d5) using a 5973 MSD operating in electron impact mode. Sixty-seven hair specimens were tested for mephedrone. Thirteen of them were found positive for mephedrone with concentrations ranging from 0.2 to 313.2ng/mg with a mean concentration of 26.8ng/mg. It was difficult to compare our findings due to a lack of reference data, nevertheless mephedrone seems well incorporated into hair (concentrations in the ng/mg range) like other stimulant drugs such as amphetamines or cocaine. The aim of this work was to develop a specific and accurate method for mephedrone analysis in hair specimens and its application to a large number of samples (n=67). The developed analytical method appears sensitive enough to reveal occasional to regular use of mephedrone. PMID- 22041624 TI - [Opportunity and challenge of sustainable development for oral and maxillofacial surgery]. PMID- 22041625 TI - [Early orthodontic treatment: indications and treatment modalities]. PMID- 22041626 TI - [Association of methylenetetrahydrofolate reductase A1298C polymorphisms with non syndromic cleft lip with or without cleft palate]. AB - OBJECTIVE: To investigate the association between a polymorphism of methylenetetrahydrofolate reductase with Non-syndromic cleft lip with or without cleft palate (NSCL/P) in Chinese population. METHODS: The polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) technique was used to detect a single nucleotide polymorphism (SNP), rs1801131, at the methylenetetrahydrofolate reductase (MTHFR) gene in both 158 patients with NSCL/P and 192 healthy individuals. The Hardy-Weinberg equilibrium for genotypic distributions was estimated by the goodness-of-fit test. The UNPHASED program was applied to perform the association analysis. RESULTS: The genotypic distribution of A1298C was not deviated from the Hardy-Weinberg equilibrium in both controls and patients. No association was found between cleft lip with or without palate (CL/P) and controls. There was significant difference of cleft palate only (CPO) and the healthy individuals (chi(2) = 4.256, P = 0.039). The frequency of AC + CC genotype was higher in control group than that in CPO group (OR = 0.8, 95%CI = 0.381 - 1.683), 26 among 100 healthy individuals carried AC + CC genetypes, which were carried by 22% of CPO patients. CONCLUSIONS: The polymorphism of MTHFR A1298C may be involved in the occurrence of non-syndromic cleft palate only in Chinese population. PMID- 22041627 TI - [Pilot clinical study of the dental cone beam CT examination before the impacted mandibular third molar extraction]. AB - OBJECTIVE: To evaluate the diagnostic accuracy of the cone beam computed tomography (CBCT) in judging the relationship between the impacted mandibular third molar (IMTM) and the inferior alveolar canal (IAC). METHODS: Sixty IMTM superimposing on the canal partially or touching the canal in line on panoramic radiograms were examined by CBCT. All CBCT images of these cases were observed by two dentists respectively. Then, all these IMTM were extracted by minimally invasive surgery, and the conditions of the IMTM sockets were observed. Two dentists observed the CBCT images independently and reached a consensus. Diagnosis test was performed in this study. RESULTS: Eight IMTM sockets were bleeding during the extracted operation, and whether the IAC wall was broken could not be judged. The other 52 IMTM sockets were clear and the walls of IAC were broken in 29 IMTM extractions. The sensitivity, specificity, Youden index, positive predictive value and negative predictive value of CBCT were 82.8%, 87.0%, 88.9% and 80.0% respectively. The diagnostic accuracy judged by the two dentists and Kappa coefficient were calculated as 84.6% and 0.800. CONCLUSIONS: The CBCT examination had good authenticity and reliability, and it was very helpful in predicting the actual relationship between the IMTM and IAC. PMID- 22041628 TI - [Effects of local application of zoledronic acid on bone healing of tooth extraction in rats]. AB - OBJECTIVE: To investigate the effect of local application of zoledronic acid (ZA) on the expression of type I collagen and vascular endothelial growth factor (VEGF). METHODS: Fifty-four male Wistar rats were divided into ZA group, gelatin sponge group, and blank control group after one-side tooth extraction. The expression of type I collagen and VEGF were detected with SP immunohistochemistry method 1, 2 and 4 weeks after operation. RESULTS: The gray value of type I collagen in ZA group (60.00 +/- 1.81, 63.47 +/- 3.02) was lower than those in gelatin sponge group (68.58 +/- 2.90, 71.15 +/- 5.57) and blank control group (69.16 +/- 9.63, 72.50 +/- 4.10, P < 0.05) in the 1 and 2 week. In the ZA and gelatin sponge groups, the gray values of type I collagen were higher in the 4th week than in the 1st and 2nd week (P < 0.05). The expression of VEGF was higher in ZA group (69.93 +/- 2.74) than in gelatin sponge group (60.86 +/- 4.79) and blank control group (61.52 +/- 2.28) in the 1st week (P < 0.05). There was significant difference in VEGF expression between the 2nd week and 1st and 4th week (P < 0.05). CONCLUSIONS: Local application of ZA could enhance the expression of type I collagen but inhibit the expression of VEGF in the early stage. PMID- 22041629 TI - [Effects of interleukin-1beta on mineralization potential of dental pulp stem cells]. AB - OBJECTIVE: To investigate the effects of pro-inflammatory cytokine interleukin 1beta (IL-1beta) on mineralization potential of dental pulp stem cells (DPSC). METHODS: Rat DPSC were cultured in vitro and randomly divided into three groups, IL-1beta (10 ug/L), osteogenic inductive medium and non-osteogenic inductive medium. After 3, 7, and 12 days of treatment, the cultures were evaluated for cell proliferation and calcium deposit. Real-time polymerase chain reaction was used to detect the gene expression levels of osteocalcin (OC), bone sialoprotein (BSP), dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP-1). In vivo test, after 3 day's treatment with IL-1beta, the cell-scaffold complexes were implanted subcutaneously in mice for 8 weeks. Histological analysis was performed to evaluate hard tissue formation. RESULTS: In vitro test, after 3 day's treatment, IL-1beta improved cell proliferation to 137.22 DNA ug/L and cell viability becomes (97.12 +/- 7.18)% of control. The gene expression levels of OC, BSP, DSPP and DMP-1 are (378.19 +/- 16.22)%, (427.12 +/- 18.22)%, (247.19 +/- 10.11)% and (198.29 +/- 10.23)% respectively. The results of IL-1beta's group was notable increased compared with non-osteogenic induction medium and the statistical differences are significant. IL-1beta induced the odontogenic differentiation of DPSC. However, these effects tended to continuously decrease with treatment time. Histological analysis demonstrated that in the group treated with IL-1beta hard tissue was markedly formed in vivo. CONCLUSIONS: IL-1beta may induce the mineralization of DPSC and play an important role in host defenses and tissue repair. PMID- 22041630 TI - [Effects of muramyl dipeptide on the differentiation of human dental pulp cells]. AB - OBJECTIVE: To investigate the nucleotide-binding oligomerization domain-2 (NOD-2) gene expression in deep caries and the effects of NOD-2 agonist muramyl dipeptide (MDP) on the differentiation of human dental pulp cells (hDPC). METHODS: NOD-2 gene level in deep caries and healthy pulp tissue was determined by real-time quantitative polymerase chain reaction (realtime-PCR). Realtime-PCR, Western blotting and immunofluorescence were performed to evaluate NOD-2 gene and protein expression. Dentin sialoprotein (DSP) protein level was assessed when hDPC were challenged by different concentrations of MDP for 24 hours, and sialophosphoprotein (DSPP), osteocalcin (OCN) mRNA and osteopontin (OPN) protein level were detected at different time points after incubation with 0.1 mg/L MDP. RESULTS: NOD-2 mRNA level was higher in pulp tissue of deep caries (0.2610 +/- 0.0824) than that in healthy controls (0.0024 +/- 0.0002), P < 0.05. The expression of NOD-2 gene and protein increased in a time denpendent manner upon stimulation with MDP. Immunofluorescence confirmed that NOD-2 protein was located in cytoplasm. Moreover, 0.1 mg/L MDP augmented DSP protein level. DSPP and OCN mRNA were elevated with time and reached the peak at 12 h and down-regulated. OPN protein level also increased with time. CONCLUSIONS: Dental pulp NOD-2 expression are up-regulated in pulp tissue of deep caries. MDP may be related to the differentiation of hDPC. PMID- 22041631 TI - [Three-dimensional finite element analysis of maxillary incisor retraction with step-shaped vertical closing loop]. AB - OBJECTIVE: To investigate the displacement and stress distribution of upper incisors in three-dimensional (3D) space controlled by step-shaped vertical closing loop. METHODS: The maxillary teeth and alveolar bone of a volunteer with normal occlusion were scanned with 3D spiral CT. Modeling and calculation were only carried out on right upper central incisor, lateral incisor and their alveolar bone in order to simplify the procedures. A 3D finite element model of archwire-brackets-upper incisors and periodontal tissues was developed using Ansys finite element package. Finally, a 3D finite element model of archwire brackets-upper incisors and periodontal tissues was established based on mirror symmetry principle. The displacement of maxillary incisors and stress distribution in periodontal tissues were analyzed. RESULTS: When step-shaped vertical closing loop was simply drew back 1 mm, the maximum displacement of upper central incisor in labial and lingual direction were 5.29 * 10(-2) and 0.71 * 10(-2) mm; 10.47 * 10(-3) and 10.20 * 10(-3) mm in gingival and occlusal direction, 10.26 * 10(-3) and 1.63 * 10(-3) mm in medial and distal direction; the maximum displacement of upper lateral incisor in labial and lingual direction were 3.31 * 10(-2) and 0.41 * 10(-2) mm, 10.52 * 10(-3) and 5.10 * 10(-3) mm in gingival and occlusal direction, 6.29 * 10(-3) and 4.64 * 10(-3) mm in medial and distal direction, the displacement trend of them were moving lingually and gingivally similar to bodily movement. The stress peach of upper central incisor, periodontal ligament and alveolar bone were 31.35, 2.52 and 4.64 MPa, the stress peach of upper lateral incisor, periodontal ligament and alveolar bone were 19.59, 1.28 and 4.12 Mpa, the stress distribution of them were similar and the periodontal ligament buffered the stress imposed on the tooth. PMID- 22041632 TI - [Application of computer aided design-computer aided manufacture technique in mandible defect reconstruction with individual titanium prosthesis]. AB - OBJECTIVE: To investigate the application of computer aided design-computer aided manufacture (CAD-CAM) technique in the reconstruction of mandible defect with individual titanium prosthesis. METHODS: Six patients with large mandibular ramus and angle tumor were spiral CT scanned preoperatively, and the CAD-CAM was used to design and make individual titanium prosthesis for reconstructing the mandibular defects after resection of the tumor. The prosthesis were assembled during operation. Postoperative follow-up period was 9 - 38 months. RESULTS: The design and manufacture of titanium prosthesis by use of CAD-CAM technique was convenient and the prosthesis fitted the defects very well. The outline of the face, the occlusion and function were restored. After 9 - 38 months of follow-up, the mandibular symmetry was good. CONCLUSIONS: The application of CAD-CAM provided accurate simulation and fast manufacturing process for the titanium prosthesis in the repair of mandibular defect. PMID- 22041633 TI - [The acceleration of titanium implant osseointegration by low intensity pulsed ultrasound: an experimental study in rats]. AB - OBJECTIVE: To establish an animal model of titanium implant and to investigate the effects of low intensity pulsed ultrasound (LIPUS) on the implant osseointegration. METHODS: Twenty-four female Sprague Dawley (SD) rats were used. Titanium implants were inserted into tibia metaphysis bilaterally in each SD rat. Since the second day following implant surgery, LIPUS stimulation were carried out around the implant on the right side for 20 minutes per day, and implants on the left side remain untouched as self-control. Eight rats were sacrificed and tibiae specimens were harvested on the end of the 4th, 8th, and 12th week respectively. X-ray picture, micro-CT analysis and histological sections were performed to evaluate the effects of LIPUS on the implant osseointegration. RESULTS: Osseointegration at the interface between the implant and bone tissue was observed bilaterally. In the micro-CT histomorphometry analysis, the percentage of osseointegration (%OI) of experiment side were (45.708 +/- 3.316)%, (46.231 +/- 1.954)%, and (46.807 +/- 1.451)% on the end of the 4th, 8th, and 12th week. Meanwhile, the %OI of control side were (43.021 +/- 3.558)%, (44.272 +/- 3.023)%, and (44.894 +/- 4.215)% respectively. The %OI on the 4th weekend, bone volume ratio (BV/TV) on the 4th and 8th weekend, trabecular thickness (Tb. Th) and degree of anisotropy (DA) on the 8th and 12th weekend of the experiment side tibia were significantly greater than those on the control side (P < 0.05). The histological examination showed that the thickness of new bone around the implant and the bone-implant contact area was obviously greater in the LIPUS treated side compared to the control side. CONCLUSIONS: The LIPUS therapy may accelerate the bone healing and osseointegration at the interface between titanium implant and bone, and promote remodeling of bone trabecula on the early stage. PMID- 22041634 TI - [Low intensity pulsed ultrasound combined with guided tissue regeneration for promoting the repair of defect at canines periodontal fenestration in Beagle dogs]. AB - OBJECTIVE: To evaluate the effects of low intensity pulsed ultrasound (LIPUS) combined with guided tissue regeneration (GTR) for the repair of the periodontal fenestration defect at the canines in Beagle dogs. METHODS: Four Beagle dogs were used for establishing the periodontal fenestration defect. Sixteen canines of four Beagle dogs were simple randomly assigned into experimental group 1 [LIPUS (60 mW/cm(2), 20 min/d) irradiation + GTR + the periodontal fenestration defect], experimental group 2 [LIPUS (60 mW/cm(2), 20 min/d) irradiation + the periodontal fenestration defect], experimental group 3 (GTR + the periodontal fenestration defect) and control group (the periodontal fenestration defect). Experiments conducted 28 d. The temperature of the gingive's surface of each group was tested every 14 days (analyzed by Wilcoxon rank sum test with SPSS 13.0). The demineralized bone tissue slices of the periodontal fenestration were obtained for histologic staining after 4 weeks treatment. RESULTS: Clinically all the treatment groups healed well. The change of gingive's surface temperature [M(Q)] before and after LIPUS irradiating were: 0.225 (0.463) degrees C (experimental group 1), 0.265 (0.133) degrees C (experimental group 2), 0.090 (0.115) degrees C (experimental group 3); -0.175 (0.370) degrees C (control group). The P value of experimental group 1 and 2 with pre-and post-treatment each time were both 0.027. Histology of the demineralized bone tissue revealed that in experimental group 1, the bone defect was filled with fresh bone-like tissues, proliferatively active osteoblasts and newly formed cementum-like tissues along the defect surface. In experimental group 3, there were more new cementum- and bone-like tissues than in experimental group 2 and control group. In experimental group 2, the new bone collagen was more mature than in experimental group 3 and control group. In control group, there was less growth of new cementum along the notch, and the new bone collagen was immature. CONCLUSIONS: LIPUS combined with GTR may have the potential of promoting the repair of periodontal fenestration defect. PMID- 22041635 TI - [Expression of excision repair cross-complementation gene in drug-resistant process of carboplatin administration in tongue squamous cell cancer (Tca8113)]. AB - OBJECTIVE: To investigate the correlations between the resistant degree of Tca8113 agaist carboplatin and the expression of excision repair cross complementation 1 (ERCC-1). METHODS: Tca8113 cells were exposed in the carboplatin solutions of gradually increasing concentration. Cancer cells were divided into six experimental groups and a control group. In the course of culture, the half inhibitory concentration (IC(50)) of each groups were detected by methyl thiazolyl tetrazolium (MTT). The expressions of ERCC-1 at mRNA and protein level were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: With the increase of drug resistance, the expression of ERCC-1 increased gradually at mRNA level (control group: 0.84 +/- 0.06, group 1: 0.96 +/- 0.06, group 2: 1.07 +/- 0.11, group 3: 1.13 +/- 0.09, group 4: 1.19 +/- 0.08, group 5: 1.29 +/- 0.07, group 6: 1.47 +/- 0.08), values between neighboring or interval groups have significant differences (P < 0.05); the expression of ERCC-1 increased gradually at protein level (control group: 0.69 +/- 0.05, group 1: 0.86 +/- 0.04, group 2: 1.01 +/- 0.04, group 3: 1.24 +/- 0.09, group 4: 1.44 +/- 0.14, group 5: 1.56 +/- 0.19, group 6: 1.88 +/- 0.22), values between neighboring or interval groups have significant differences (P < 0.05). The gradually increasing RT-PCR gray values were related to the gradually increasing IC(50) in all groups (r = 0.91, P < 0.01), and the gradually increasing western blotting gray values were also related to the gradually increasing IC(50) in all groups (r = 0.88, P < 0.01). CONCLUSIONS: The high expression of ERCC-1 may become an indicator of Tca8113 resisting carboplatin. This might provide a potential target to reverse tongue squamous cell cancer (Tca8113) that has resistance to carboplatin. PMID- 22041636 TI - [Fiber post and its key point of application]. PMID- 22041637 TI - Timing of coronary angiography and outcome in patients with non-ST elevation acute coronary syndromes and kidney disease: real-world data from the acute coronary syndromes Israeli survey. AB - OBJECTIVE: Patients with kidney disease (KD) who present with non-ST segment elevation acute coronary syndromes (NSTE-ACS) may benefit from coronary intervention. We evaluated the outcome of these patients who were referred for early or late coronary angiography. METHODS: The risk of 1-year mortality according to the presence of KD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)] and the time of coronary angiography [categorized as early (<=48 h from admission) or late (>48 h from admission)] was assessed among 2,001 NSTE-ACS patients enrolled in the ACS Israeli Survey between 2004 and 2008. A propensity score for early angiography was included in the proportional hazards modeling of mortality. RESULTS: Patients with KD (n = 729) experienced a 2.7-fold increased risk of death compared with non-KD patients (p < 0.001). Early coronary angiography was associated with a lower rate of in-hospital complications and 30 day mortality. Both early and late angiography were associated with a lower adjusted risk of 1-year mortality [hazard ratios (HRs) 0.46 (p < 0.001) and 0.59 (p = 0.002), respectively] compared with no angiography. In patients with severe KD (eGFR <30 ml/min/1.73 m(2)), only early coronary angiography was associated with a lower mortality risk (HR 0.25, 95% confidence interval 0.08-0.81). CONCLUSIONS: An early invasive strategy is associated with a low mortality risk in NSTE-ACS patients with KD and a more pronounced effect among those with severe KD. PMID- 22041638 TI - Utilizing environmental, socioeconomic data and GIS techniques to estimate the risk for ascariasis and trichuriasis in Minas Gerais, Brazil. AB - The impact of intestinal helminths on human health is well known among the population and health authorities because of their wide geographic distribution and the serious problems they cause. Geohelminths are highly prevalent and have a big impact on public health, mainly in underdeveloped and developing countries. Geohelminths are responsible for the high levels of debility found in the younger population and are often related to cases of chronic diarrhea and malnutrition, which put the physical and intellectual development of children at risk. These geohelminths have not been sufficiently studied. One obstacle in implementing a control program is the lack of knowledge of the prevalence and geographical distribution. Geographical information systems (GIS) and remote sensing (RS) have been utilized to improve understanding of infectious disease distribution and climatic patterns. In this study, GIS and RS technologies, as well as meteorological, social, and environmental variables were utilized for the modeling and prediction of ascariasis and trichuriasis. The GIS and RS technologies specifically used were those produced by orbital sensing including the Moderate Resolution Imaging Spectroradiometer (MODIS) and the Shuttle Radar Topography Mission (SRTM). The results of this study demonstrated important factors related to the transmission of ascariasis and trichuriasis and confirmed the key association between environmental variables and the poverty index, which enabled us to identify priority areas for intervention planning in the state of Minas Gerais in Brazil. PMID- 22041640 TI - Laparoscopic adrenalectomy: Single centre experience. AB - BACKGROUND: Laparoscopic adrenalectomy is an attractive alternative to the traditional open approach in the surgical excision of an adrenal gland. It has replaced open adrenalectomy in our institution and we review our experience to date. METHODS: All cases of laparoscopic adrenalectomies in our hospital over eight years (from 2001 to May 2009) were retrospectively reviewed. Patient demographics, diagnosis, length of hospital stay, histology and all operative and post-operative details were evaluated. RESULTS: Fifty-five laparoscopic adrenalectomies (LA) were performed on 51 patients over eight years. The mean age was 48 years (Range 16-86 years) with the male: female ratio 1:2. Twenty-three cases had a right adrenalectomy, 24 had a left adrenalectomy and the remaining four patients had bilateral adrenalectomies. 91% were successfully completed laparoscopically with five converted to an open approach. Adenomas (functional and non functional) were the leading indication for LA, followed by phaeochromocytomas. Other indications for LA included Cushing's disease, adrenal malignancies and rarer pathologies. There was one mortality from necrotising pancreatitis following a left adrenalectomy for severe Cushing's disease, with subsequent death 10 days later. CONCLUSION: Laparoscopic adrenalectomy is effective for the treatment of adrenal tumours, fulfilling the criteria for the ideal minimally invasive procedure. It has replaced the traditional open approach in our centre and is a safe and effective alternative. However, in the case of severe Cushing's disease, laparoscopic adrenalectomy has the potential for significant adverse outcomes and mortality. PMID- 22041641 TI - Acute pancreatitis in the elderly - Can we perform better? AB - BACKGROUND: Despite age traditionally being a criterion for stratification of severity in acute pancreatitis (AP), the condition is not common in the elderly population (>80 years) and very few studies have examined outcome in this cohort. The aim of this study was to evaluate our experience and outcome in this expanding population. METHODS: A retrospective analysis was performed of all patients over 80 years of age who were admitted with AP (defined as a serum amylase >400 IU/L) between January 2004 and January 2007. The modified Glasgow score was used for severity stratification. RESULTS: Forty patients with AP were admitted during the study period, of whom 23 were females. The mean age was 84 (SD 4.1) years. Fifteen patients (37%) had severe AP as indicated by a Glasgow score of 3 or more. The aetiologies were gallstones (n = 28; 70%), drug-induced (n = 4; 10%) and idiopathic (n = 8; 20%). Ten patients (25%) died during their initial admission to hospital, of whom 5 died before undergoing any form of imaging to determine the cause of AP. Six patients, 5 of whom had gallstones were subsequently readmitted with a further attack of AP. Eleven patients underwent an ERCP during their initial admission and a further 4 patients underwent ERCP during their subsequent admission. Only 3 patients with gallstone-induced AP underwent a cholecystectomy, all performed laparoscopically. CONCLUSIONS: AP in octogenarians is a significant problem and carries a high mortality irrespective of the Glasgow severity score. Early intervention by means of ERCP is indicated to try and improve outcome in this group with biliary pancreatitis. Laparoscopic cholecystectomy must be considered as a definitive treatment in these patients as available evidence suggests that this can be performed with acceptable morbidity and mortality in this group. PMID- 22041642 TI - Does using the WHO surgical checklist improve compliance to venous thromboembolism prophylaxis guidelines? AB - BACKGROUND: Using the World Health Organisation (WHO) surgical checklist has been shown to improve the safety of patients undergoing surgery. Its effect on the compliance to venous thromboembolism (VTE) guidelines has not been established before. Our objective was to assess if using the WHO checklist improved compliance to VTE prophylaxis guidelines. METHODS: Compliance to NICE VTE guidelines were prospectively assessed in all general surgery patients over two separate audit periods, before and after 6 months of the routine use of the WHO checklist. Correct completion of the checklist was verified. RESULTS: 370 patients (173 [47%] male, 197 [53%] female, mean age 61.6 yrs). Non compliance to NICE VTE guidelines was reduced form 16/233 (6.9%) to 3/137 (2.1%) after introduction of the checklist (p = 0.046 Fisher exact test). Non compliance was reduced in both emergency and elective procedures. CONCLUSIONS: Establishment of the WHO checklist for routine use in all general surgery patients may significantly improve VTE guideline compliance of all general surgery patients. PMID- 22041643 TI - Specialist anatomy: Is the structure of teaching adequate? AB - BACKGROUND: A knowledge and understanding of specialist anatomy, which includes radiological, laparoscopic, endoscopic and endovascular anatomy is essential for interpretation of imaging and development of procedural skills. METHODS AND MATERIALS: Medical students, specialist trainees and specialists from the London (England, UK) area were surveyed to investigate individual experiences and recommendations for: (1) timing of the introduction of specialist anatomy teaching, and (2) pedagogical methods used. Opinions relating to radiological, laparoscopic, endoscopic and endovascular anatomy were collected. Non-parametric tests were used to investigate differences in recommendations between specialist trainees and specialists. RESULTS: Two hundred and twenty-eight (53%) individuals responded to the survey. Imaging was most commonly used to learn radiological anatomy (94.5%). Procedural observation was most commonly used to learn laparoscopic (89.0%), endoscopic (87.3%) and endovascular anatomy (66.2%). Imaging was the most recommended method to learn radiological anatomy (92.1%). Procedural observation was the most recommended method for learning laparoscopic (80.0%), endoscopic (81.2%) and endovascular anatomy (42.5%). Specialist trainees and specialists recommended introduction of specialist anatomy during undergraduate training. CONCLUSION: Although the methods for specialist anatomy learning are in practice, there is no consensus on timing and structure within the anatomy curriculum. Recommendations from trainees and specialists should be considered so that the existing curriculum can be refined to maximise learning outcomes. PMID- 22041644 TI - Femoral neck fractures in patients on Clopidogrel. The effect of delaying surgery and the introduction of the new SIGN guidelines. AB - INTRODUCTION: Femoral neck fractures are an increasingly common injury in the elderly. Frequently these patients present taking Clopidogrel, an irreversible inhibitor of platelet aggregation. Although this is associated with an increased risk of intra-operative bleeding and also an increased risk of spinal haematoma where regional anaesthesia is employed, the recent SIGN (Scottish Intercollegiate Guidance Network) guidelines recommend that surgery should not be delayed. METHODS: We conducted a retrospective review of consecutive patients admitted with femoral neck fractures between April 2008 and October 2009. Patients on Clopidogrel were identified and data including ASA grade, time to operation, medical co-morbidities, and post-admission complications were recorded. Comparative information from the National Hip Fracture Database was used. RESULTS: 405 patients were included. 27 patients were taking Clopidogrel on admission and they were all ASA 3 or 4. Mean time to theatre was 8 days. Post admission medical complications occurred in 7 patients (25.9%). A further 4 patients (14.8%) died, 3 of them post-operatively. From the study population a control group of 72 ASA 3 and 4 patients was further studied. The mean time to operation was 2.3 days. Post-admission medical complications occurred in 13 patients (18%) and 8 patients (11%) died post-operatively. The difference in the mortality and morbidity of these two groups was found to be statistically not significant. In 2009 the national mean time to operation was 2.19 days with an associated mortality rate of 8.67%. DISCUSSION AND CONCLUSION: Patients receiving Clopidogrel have complex medical co-morbidities and a higher anaesthetic risk. Delaying operative management might be contributing to the increased rate of mortality and morbidity. In accordance with the SIGN guidelines we recommend early operative intervention in these high risk patients. PMID- 22041645 TI - Study on the feasibility of provision of distance learning programmes in surgery to Malawi. AB - Medical educational opportunities and resources are considerably limited in the developing world. The expansion of computing and Internet access means that there exists a potential to provide education to students through distance learning programmes. This study investigated the feasibility of providing distance learning course in surgery in Malawi. The study investigated the user requirements, technical requirements and Internet connections in two teaching hospitals in Malawi. In addition the appropriateness of current course material from the Edinburgh Surgical Sciences Qualification to Malawi trainees was assessed. The study found a high degree of interest from Malawian trainees in distance learning. The provision of basic science modules such as anatomy and physiology and the ability to access journals were considered highly desirable. The current ESSQ course would require extensive re-modelling to make it suitable to an African trainee's requirements. Internet speeds remain slow and access is currently expensive. There is considerable interest in distance learning programmes in Malawi but access to them is limited partly because of slow and expensive Internet access. Understanding the needs of trainees in countries such as Malawi will allow better direction of educational aid and resources to support surgical training. PMID- 22041646 TI - Gene therapy in vascular disease. AB - BACKGROUND AND PURPOSE OF THE STUDY: Peripheral artery disease is a highly prevalent disease which is characterised by high unmet medical need particularly in the more advanced stages of disease. Options comprise the need for vessel regeneration using therapeutic angiogenic gene therapy as well as the prevention of restenosis post-angioplasty using local gene therapy. Both problems have been addressed by extensive research. Recent advances in the knowledge of the complex regulation of angiogenesis and arteriogenesis and ways to its induction offer hope for a novel strategy that is based on the generation of such new vessels. This strategy termed "therapeutic angiogenesis" is a concept based on the use of angiogenic factors or stem cells or their combination to promote neovascularisation for the treatment of ischaemic tissues. This manuscript summarises the development of therapeutic angiogenic strategies using gene therapy. METHODS: Review of current publications of phase I, II and III clinical trials and websites. MAIN FINDINGS: Phase II trials performed so far are difficult to compare due to different genes, vectors and applications routes used and different endpoints evaluated. Recently, the largest phase III trial did not confirm efficacy of non-viral gene transfer using the gene for fibroblast growth factor 1 in critical limb ischaemia. CONCLUSIONS: Cardiovascular gene therapy, particularly, therapeutic angiogenesis has been shown to be safe, however, did not prove consistently efficacious in randomised controlled trials. PMID- 22041647 TI - Bionic prosthetic hands: A review of present technology and future aspirations. AB - BACKGROUND: Bionic prosthetic hands are rapidly evolving. An in-depth knowledge of this field of medicine is currently only required by a small number of individuals working in highly specialist units. However, with improving technology it is likely that the demand for and application of bionic hands will continue to increase and a wider understanding will be necessary. METHODS: We review the literature and summarise the important advances in medicine, computing and engineering that have led to the development of currently available bionic hand prostheses. FINDINGS: The bionic limb of today has progressed greatly since the hook prostheses that were introduced centuries ago. We discuss the ways that major functions of the human hand are being replicated artificially in modern bionic hands. Despite the impressive advances bionic prostheses remain an inferior replacement to their biological counterparts. Finally we discuss some of the key areas of research that could lead to vast improvements in bionic limb functionality that may one day be able to fully replicate the biological hand or perhaps even surpass its innate capabilities. CONCLUSION: It is important for the healthcare community to have an understanding of the development of bionic hands and the technology underpinning them as this area of medicine will expand. PMID- 22041648 TI - A clinical review of single-incision laparoscopic surgery. AB - Laparoscopic surgery is one of the most significant surgical advances of the twentieth century. Recently, the focus has been on the development of minimally invasive techniques in the form of single-incision laparoscopic surgery. The single-incision technique provides a less invasive alternative to conventional laparoscopic surgery, requiring only one incision disguised within the umbilical folds in contrast to the three to five incisions in conventional laparoscopic surgery. The availability of a number of specialised ports has aided the development of single-incision laparoscopic surgery, and led to its widespread use. The successful use of single-incision laparoscopic surgery has been reported for a number of surgical procedures, and offers several potential benefits versus conventional laparoscopic surgery, including reduced pain, reduced time to recovery and improved cosmesis. This review of international literature assesses the current status, as well as the experience, of single-incision laparoscopic surgery within general, colorectal, bariatric, metabolic, gynaecological and urological surgery. The challenges faced with single-incision laparoscopic surgery are discussed, as well as the clinical studies that are required in order to establish single-incision surgery as a significant improvement to conventional laparoscopic surgery in terms of reduced pain and improved cosmesis. PMID- 22041649 TI - Laparoscopic TAP block for laparoscopic cholecystectomy: Description of a novel technique. PMID- 22041650 TI - A novel traction assembly for shoulder arthroscopy. PMID- 22041651 TI - Laparoscopy through a groin hernia: An everyday application of natural orifice surgery. PMID- 22041652 TI - Red flag symptoms and signs for diagnosing perilunate dislocation. PMID- 22041653 TI - Condensation of the isoprenoid and amino precursors in the biosynthesis of domoic acid. AB - Understanding how environmental signals regulate production of domoic acid in blooms of Pseudo-nitzschia spp. at a molecular level requires description of the biochemical pathway to this kainoid neurotoxin. Precursor feeding studies have suggested domoic acid arises from the condensation of the C(10) isoprenoid geranyl diphosphate with glutamate, but the specific reactions leading to domoic acid from these precursors remain undescribed. Here, we develop a method to derivatize domoic acid with propyl chloroformate that enables gas chromatography mass spectrometry (GC-MS) analysis to measure incorporation of stable isotopes into domoic acid generated in cultures incubated with isotopically-labeled substrates. We apply this method to demonstrate that both (2)H from [1 (2)H(2)]geraniol are incorporated into domoic acid, suggesting that the condensation of geranyl diphosphate with an amino group occurs by nucleophilic substitution of the diphosphate rather than by oxidation of geraniol to the aldehyde before reaction with an amino group to form an imine. Ultimately, these and similar studies will facilitate the identification of DA biosynthetic enzymes and genes which will enable the study of how environmental factors regulate DA biosynthesis at the molecular level. PMID- 22041654 TI - Glial activation in the spinal ventral horn caudal to cervical injury. AB - Microglia and astrocytes play complex roles following spinal cord injury (SCI), contributing to inflammatory processes that both exacerbate injury and promote functional recovery by supporting neuro-protection and neuroplasticity. The crossed phrenic phenomenon (CPP) is an example of respiratory plasticity in which C(2) cervical hemisection (C(2)HS) strengthens crossed-spinal synaptic pathways to phrenic motor neurons ipsilateral to injury. We hypothesized that microglia and astrocytes are activated in the phrenic motor nucleus caudal and ipsilateral to C(2)HS, suggesting their potential for involvement in the CPP. To test this hypothesis, an incomplete cervical spinal hemisection (C(2) lateral injury; C(2)LI) was performed, and rats were allowed to recover for 1, 3, 14 or 28 days before collecting perfused spinal tissues. Microglia (via OX42) and astrocytes [via glial fibrillary acidic protein (GFAP)] were visualized with immunofluorescence microscopy in the C(4)-C(5) ventral horn, the region encompassing most of the phrenic motor nucleus. OX42-occupied fractional area ipsilateral to injury increased with C(2)LI (vs. sham) at 1 (12.5+/-1.8%, p<0.001), 3 (29.0+/-1.9%, p<0.001), 14 (26.1+/-3.1%, p<0.001) and 28 (19.2+/ 2.0%, p<0.001) days post-C(2)LI. GFAP-occupied fractional area also increased with C(2)LI at 3 (24.4+/-3.2%, p<0.001) and 14 (16.8+/-8.3%, p=0.012) days, but not at 1 (6.2+/-3.9%, p=0.262) or 28 (10.6+/-3.9%, p=0.059) days post-C(2)LI. Thus, microglia and astrocytes are activated in the phrenic motor nucleus caudal to C(2)LI, suggesting that they play a role in functional deficits and/or recovery following spinal injury. PMID- 22041655 TI - If at first you do not succeed: try another phase! Rescue reconstruction of an anomalous coronary artery in a patient with atrial fibrillation. PMID- 22041656 TI - GHRH antagonist MZ-5-156 increases the expression of AMPK in A549 lung cancer cells. AB - AMP-activated protein kinase (AMPK) regulates cellular proliferation, growth and metabolism. Targeted activation of AMPK is considered an important therapeutic strategy for cancer treatment. To evaluate the effect of growth hormone-releasing hormone (GHRH) and its antagonist MZ-5-156 on the phosphorylation of AMPK and other related regulatory intracellular proteins we employed human non-small cell lung cancer cell line A549, which expresses GHRH receptors. Treatment of A549 cells with GHRH antagonist decreased cell proliferation and activated AMPK as well as glycogen synthase kinase (GSK)3beta. Furthermore, MZ-5-156 inhibited Akt, the mammalian target of rapamycin (mTOR) and its downstream target eIF4E which controls protein synthesis and cell growth. GHRH(1-29)NH2 counteracted all these effects. HeLa human endometrial cancer cells which do not express any GHRH receptors were used as a negative control and GHRH did not induce the AMPK activation in these cells. Our results demonstrate for the first time that GHRH antagonists can regulate the AMPK metabolic pathway, which is crucial for the growth of non-small cell lung cancer and other major cancers. PMID- 22041657 TI - DNA ligase III: a spotty presence in eukaryotes, but an essential function where tested. AB - DNA ligases are crucial for most DNA transactions, including DNA replication, repair, and recombination. Recently, DNA ligase III (Lig3) has been demonstrated to be crucial for cell survival due to its catalytic function in mitochondria. This review summarizes these recent results and reports on a hitherto unappreciated widespread phylogenetic presence of Lig3 in eukaryotes, including in some organisms before the divergence of metazoa. Analysis of these putative Lig3 homologs suggests that many of them are likely to be found in mitochondria and to be critical for mitochondrial function. PMID- 22041658 TI - Epidemiology and diagnosis of multiple sclerosis. AB - Multiple sclerosis is an inflammatory disease of the CNS. The disease is predominantly diagnosed in young adults, with long-term implications for both their personal and professional lives. The economic impact of the condition is particularly significant as the majority of patients are of working age, costing the UK economy approximately L1.4 billion (McCrone et al, 2008). PMID- 22041659 TI - The critically ill patient: making the referral to intensive care. AB - Intensive care units are responsible for looking after patients with reversible life-threatening conditions, who need frequent and often invasive monitoring as well as support from mechanized equipment and pharmacological therapies to maintain normal body function and physiological parameters. A previous article highlighted how to recognize and stabilize the sick patient (Elnour and Shankar Hari, 2011). Some patients may continue to deteriorate despite appropriate and prompt intervention. This article outlines the criteria for advanced life support interventions and hence admission to critical care. The focus of discussion will be patients in need of level 2 to 3 care requiring priority 1 to 2 admissions. PMID- 22041660 TI - The Babinski sign. AB - Joseph Babinski (1857-1932), a French neurologist of Polish descent, was the first person to describe extension of the big toe following stimulation of the sole of the foot on 22 February 1896 (Babinski, 1896). He referred to the sign as 'phenomene des orteils' (toes phenomenon) but it is now usually referred to eponymously as the 'Babinski sign' or descriptively as the extensor plantar response. PMID- 22041661 TI - So you want a career in pain medicine. AB - The treatment of patients in pain is a fundamental skill of all doctors. From the junior doctor to the senior GP all will require an ability to manage the commonest presenting symptom. So why would you want to specialize in pain medicine? Well, the burden of pain is huge. Surveys estimate that almost 20% of adults in Britain are suffering from significant long-term painful symptoms. The consequences both to health of the nation and the economy are huge. But all is not lost - pain is rarely intractable and it is seldom that 'nothing can be done'. PMID- 22041662 TI - Functional calcium imaging in developing cortical networks. AB - A hallmark pattern of activity in developing nervous systems is spontaneous, synchronized network activity. Synchronized activity has been observed in intact spinal cord, brainstem, retina, cortex and dissociated neuronal culture preparations. During periods of spontaneous activity, neurons depolarize to fire single or bursts of action potentials, activating many ion channels. Depolarization activates voltage-gated calcium channels on dendrites and spines that mediate calcium influx. Highly synchronized electrical activity has been measured from local neuronal networks using field electrodes. This technique enables high temporal sampling rates but lower spatial resolution due to integrated read-out of multiple neurons at one electrode. Single cell resolution of neuronal activity is possible using patch-clamp electrophysiology on single neurons to measure firing activity. However, the ability to measure from a network is limited to the number of neurons patched simultaneously, and typically is only one or two neurons. The use of calcium-dependent fluorescent indicator dyes has enabled the measurement of synchronized activity across a network of cells. This technique gives both high spatial resolution and sufficient temporal sampling to record spontaneous activity of the developing network. A key feature of newly-forming cortical and hippocampal networks during pre- and early postnatal development is spontaneous, synchronized neuronal activity (Katz & Shatz, 1996; Khaziphov & Luhmann, 2006). This correlated network activity is believed to be essential for the generation of functional circuits in the developing nervous system (Spitzer, 2006). In both primate and rodent brain, early electrical and calcium network waves are observed pre- and postnatally in vivo and in vitro (Adelsberger et al., 2005; Garaschuk et al., 2000; Lamblin et al., 1999). These early activity patterns, which are known to control several developmental processes including neuronal differentiation, synaptogenesis and plasticity (Rakic & Komuro, 1995; Spitzer et al., 2004) are of critical importance for the correct development and maturation of the cortical circuitry. In this JoVE video, we demonstrate the methods used to image spontaneous activity in developing cortical networks. Calcium-sensitive indicators, such as Fura 2-AM ester diffuse across the cell membrane where intracellular esterase activity cleaves the AM esters to leave the cell-impermeant form of indicator dye. The impermeant form of indicator has carboxylic acid groups which are able to then detect and bind calcium ions intracellularly. The fluorescence of the calcium sensitive dye is transiently altered upon binding to calcium. Single or multi photon imaging techniques are used to measure the change in photons being emitted from the dye, and thus indicate an alteration in intracellular calcium. Furthermore, these calcium-dependent indicators can be combined with other fluorescent markers to investigate cell types within the active network. PMID- 22041663 TI - Fourth ventricular hamartoma presenting with status epilepticus treated with emergency surgery in an infant. AB - A 4-week-old infant presented with hemifacial spasms noticed from the 4th day after delivery. These progressed in severity, with generalization every 3-4 h. On admission, the infant went into refractory status epilepticus and had to be electively ventilated and taken for surgery on a semi-emergency basis. MRI showed a fourth ventricular hamartoma and video EEG showed spikes that were synchronous with the facial 'twitches' with generalization. Following the first surgery, the infant had an initial complete recovery, but developed recurrence of facial twitches after 2 weeks. Repeat MRI showed a small residual tumor which was re operated and completely excised (at 8 weeks). Following this, the patient had complete recovery from seizures (5-year follow-up). This is the youngest patient reported presenting with status epilepticus with a fourth ventricular hamartoma operated successfully. PMID- 22041664 TI - Study of the ascending lumbar and iliolumbar veins: surgical anatomy, clinical implications and review of the literature. AB - The surgical anatomy (geometrical features, metric relations, and drainage pattern) of the ascending lumbar vein (ALV) and iliolumbar vein (ILV) is clinically important. Notwithstanding, the available literature comprises but a small number of studies and a limited number of specimens involved. The present study constitutes a detailed description and classification of the drainage pattern of both these veins. The detailed anatomy of ALV and ILV was examined in both sides in 59 embalmed adult human cadavers of Caucasian origin. Cases with anatomical variations (9 cadavers) of the inferior vena cava (IVC), common iliac vein (CIV), external iliac vein (EIV) and internal iliac vein (IIV) were excluded from subsequent study and analysis. In the remaining 50 cadavers (100 sides) two main drainage types of the lower end of ALV were found. In Type I (54%, 54/100) the ALV presented the same pattern in both sides. In Type II, the ALV differed in pattern from one side to the other (46%, 46/100). Four subtypes were recorded for each Type. An ALV-ILV common trunk occurred in 15% (15/100). The percentage of variations of ALV was 34% and ILV 91%. The number of variations of the two veins differed significantly (p<0.001). No statistically significant difference was found relating to side or gender. Thorough knowledge of the surgical anatomy of ALV and ILV prevents injury, bleeding and further complication of many operations in the retroperitoneal space and pelvis. Awareness of the geometrical features of ALV and ILV helps avoiding or aids early recognition of a misplacement of a vascular catheter into the ALV during femoral vein catheterizations. PMID- 22041665 TI - Purinergic P2X3 heteroreceptors enhance parasympathetic motor drive in isolated porcine detrusor, a reliable model for development of P2X selective blockers for detrusor hyperactivity. AB - Various forms of low urinary tract symptoms (LUTS) seem dependant upon dysregulation of the purinergic pathway which produces sensory- or motor activated incontinence. A body of evidence in human urinary bladders supports a link between up-regulation of purinergic activity and the pathogenesis of detrusor instability. This study investigated the potential role of adenosine 5' triphosphate (ATP) in the control of detrusor motor drive in a model of porcine urinary bladder. The involvement of ATP on excitatory activity was assessed by measuring neurally-evoked [(3)H]-acetylcholine (ACh) release and smooth muscle contraction in detrusor strips. Epithelium-deprived preparations were used to minimize the influence of non-neural sources of ACh and ATP on parasympathetic neurotransmission. ACh release and smooth muscle contractility were not significantly affected by neural ATP in normal detrusor, but markedly enhanced when ATP hydrolysis was reduced by ectoATPase inhibitors, as well as by alpha,beta-methylene-ATP (ABMA), agonist resistant to ecto-enzymes degradation. Prejunctional P2X receptors located on cholinergic nerves are involved in such potentiating effect. These purinergic heteroreceptors were characterized as P2X(3) subunits by means of the putative antagonists: NF449 (P2X(1,3) selective), NF023 (P2X(1,3) selective), PPNDS (P2X(1) selective) and A-317491 (P2X(3) selective). In porcine detrusor, P2X(3) receptors are functionally expressed at neural site facilitating neurogenic ACh release. When purine breakdown is experimentally down-regulated to mimicking the impaired purinergic pathway observed in pathological human bladders, endogenous ATP can markedly enhance detrusor contractility through activation of these receptors. Since P2X(3) blockade represents a potential therapeutic approach for diseases of the urinary tract, isolated porcine detrusor represents a reliable model for development of novel selective P2X(3) antagonists beneficial in the treatment of detrusor hyperactivity. PMID- 22041666 TI - Limonoids from the fruits of Melia toosendan. AB - Fifteen limonoids, meliatoosenins E-S (1-15), and 10 known compounds were isolated from the fruits of Melia toosendan. Their structures were elucidated on the basis of extensive spectroscopic methods including DEPT, HSQC, HMBC, (1)H (1)H COSY, and ROESY experiments. All the compounds were evaluated for antiproliferative activity using A-549 and HL-60 cell lines. PMID- 22041667 TI - [Efforts to promote the innovation and development of arthroscopic surgery of China]. PMID- 22041668 TI - [International developing tendency and the rise of China in arthroscopic surgery]. PMID- 22041669 TI - [Both the medial and lateral meniscal allograft transplantation following the anterior cruciate ligament reconstruction by arthroscopic surgical technique]. AB - OBJECTIVE: To discuss the minimal invasive arthroscopic surgery technique and clinical results of both the medial and lateral meniscal transplantation following the anterior cruciate ligament reconstruction with double bundles and bone tunnels. METHODS: In August 2008 a minimal invasive surgery of both the medial and lateral meniscal allograft transplantation following anterior cruciate ligament reconstruction was preformed for 1 case with both the medial and lateral meniscectomy by arthroscopic surgery. The method of two bone plugs attached on tibial plateau was employed for medial meniscal allograft transplantation and the technique the bridge in slot for lateral meniscal allograft transplantation. The VAS, Lysholm score and IKDC rating were recorded before and after operation. The stability of knee was assessed by Lachman test, drawer sign and pivot shift test. RESULTS: The patient was followed up 26 month after the operations. The degrees of knee flexion, extension and function of walk were normal. The Lachman test, drawer sign and pivot shift test were nearly normal. The VAS after operation was 2 points lower than that before operation. The Lysholm score post-operation was 20 points higher than pre-operation. The IKDC became B degree in late following up from C degree before the operation. MRI revealed anterior cruciate ligament graft was continuous and the meniscal allograft was normal shape on year 1 after the operation. The posterior horn of medial meniscal allograft and anterior corner of lateral meniscal allograft showed slightly shrunk. The second-look arthroscopy showed that the healing occurring between meniscal allograft and the capsule and meniscal allograft was normal shape on month 18 after the operation. The anterior horn of medial and lateral meniscus was slightly worn. CONCLUSIONS: Both the medial and lateral meniscal transplantation following the anterior cruciate ligament reconstruction in appropriately selected patients with the medial and lateral meniscus-deficient knee may recover the knee mechanic balance and stability, which is a option of treatment for that young and activity patients. It is proposed that the medial and lateral meniscal grafts harvested from a single donator. Attention should be paid to the direction of the bone tunnels fixing the horns of the meniscus in order to avoid communication with the tunnels of anterior cruciate ligament reconstruction. PMID- 22041670 TI - [Arthroscopic anterior cruciate ligament reconstruction with remnant preservation: a prospective comparison study]. AB - OBJECTIVE: To evaluate the clinical significance of arthroscopic anterior cruciate ligament (ACL) reconstruction using the remnant-preserved technique. METHODS: From August 2008 to September 2009, 70 cases with the remnant of injured ACL were included in the trials, which were randomized into the remnant preservation (RP) group and the control group, 35 cases in each group. All patients in the two groups underwent arthroscopic ACL reconstruction surgeries, with ACL-remnant preserving technique in RP group and ACL-remnant resection in control group, respectively. The injured ACL was reconstructed with allograft in all cases. Postoperative follow-up assessment included the International Knee Documentation Committee (IKDC) grading and Lysholm score, Lachman test, pivot shift test and KT-1000 measurement, proprioception measurements and the arthroscopic second look evaluation. RESULTS: Sixty-one (61/70, 87%) cases were available for an average of 13.1 months follow-up assessment postoperatively. There were no significant differences between the RP and control group in functional outcome as evaluated with Lysholm score (96.4 vs. 94.9, P = 0.71) and IKDC grading (cases with A and B gradings: 30 vs. 29, P = 0.586). Regarding objective stability, there were no differences between the 2 group in mean side to-side difference of KT-1000 (1.69 mm vs. 1.65 mm, P = 0.83), Lachman test (negative cases: 29 vs. 28, P = 1.00) and pivot shift test (negative cases: 31 vs. 27, P = 0.225). There was also no difference between the groups in proprioception evaluation measured with angle repetitive test (4.56 degrees vs. 4.28 degrees , P = 0.522). During second look arthroscopic examination, the grafts synovial coverage rates were found to be 85% in the RP group and 84.2% in the control group, without significant difference (P > 0.05). CONCLUSIONS: Arthroscopic ACL reconstruction with the remnant preserving technique using tendon allograft do not improve the postoperative knee-joint function scores, stability, proprioception and synovial coverage of grafts. PMID- 22041671 TI - [Arthroscopic single-bundle anterior cruciate ligament reconstruction with six strand hamstring tendon and patellar tendon allograft]. AB - OBJECTIVE: To compare the outcome of arthroscopic single-bundle anterior cruciate ligament (ACL) reconstruction with six-strand hamstring tendon and patellar tendon allograft. METHODS: From October 2006 to December 2009, 108 patients with arthroscopic single-bundle ACL reconstruction were retrospectively reviewed, with 58 patients with six-strand hamstring tendon (Group H), and 50 patients with patellar tendon allograft (Group P). Patients were available for clinical evaluation with KT-1000 arthrometer measurements, Lachman and pivot-shift test, and knee function with the International Knee Documentation Committee (IKDC), Lysholm scores. RESULTS: All the patients were followed up at an average of 28.6 months (range 12 - 38 months). The average side-to-side difference was lesser for group H (1.2 +/- 1.2) mm than group P (1.8 +/- 1.5) mm (P < 0.05). On the pivot shift test, 55 (94.8%) patients were negative and 3 (5.2%) were positive in group H, whereas 41 (82.0%) were negative and 9 (18.0%) were positive in group P, with significant difference between two groups (P < 0.05). All knee function scores were improved postoperatively, without statistically significant difference between the two groups (P > 0.05). CONCLUSION: Arthroscopic single-bundle ACL reconstruction with six-strand hamstring tendon will achieve better knee stability than patellar tendon allograft. PMID- 22041672 TI - [Arthroscopic Bankart repair with suture anchors: results and risk factors of recurrence of instability]. AB - OBJECTIVE: To evaluate retrospectively the results of arthroscopic Bankart repair using suture anchors for recurrent anterior shoulder dislocation with a minimum 1 year follow-up and to assess risk factors for recurrence. METHODS: From March 2002 to March 2010, 259 patients with recurrent anterior shoulder dislocation underwent arthroscopic Bankart repair with suture anchors. And 188 patients (50 athletes, 138 nonathletes) were available for follow-up. The mean age at the time of surgery was 25.3 years (range, 13 - 58 years). The mean follow-up was 38.6 months (range, 12 - 110 months). All of the 188 patients were evaluated preoperatively and postoperatively with the American Shoulder and Elbow Society (ASES) shoulder score and Rowe score system. The rate of recurrent instability, range of motion, and risk factors for postoperative recurrence were evaluated. The ASES score was 72.6 preoperatively, and Rowe score was 33.4. RESULTS: The ASES scores improved significantly to 91.9 postoperatively (P < 0.001). The Rowe scores improved to 81.9 postoperatively (P < 0.001). And 152 patients were greatly satisfied with the results, 16 satisfied and 20 unsatisfied. The satisfactory rate was 89.4%. 24 patients (12.8%) suffered a recurrence after surgery, 14 athletes and 10 nonathletes. The recurrence rates were 28.0% in the athlete group and 7.2% in the nonathlete group. On average there was no significant loss of external rotation postoperatively (average, 75.2 degrees preoperatively and 67.2 degrees postoperatively). Patients under age 20, and athlete patients were associated with recurrence (P < 0.05). Other factors including length of time until surgery, type of anchors, number of anchors, presence of bony Bankart lesion, presence of a superior labrum, anterior and posterior tear, presence of posterior or inferior labrum lesion, presence of rotator cuff tear, ligamentous laxity and rotator interval closure did not influence the recurrence rate (P > 0.05). CONCLUSIONS: Arthroscopic Bankart repair is a good option for the treatment of recurrent anterior shoulder dislocation. Identification of risk factors for recurrence allows for consideration of open stabilization. In the series, patients under age 20 and athlete patients are the most important risk factors for recurrence. PMID- 22041673 TI - [Clinical results after all arthroscopic reduction and fixation of bony Bankart lesion]. AB - OBJECTIVE: To investigate the shoulder function after arthroscopic reduction and internal fixation in patients with bony Bankart lesion. METHODS: Between May 2004 and May 2008, 45 patients with bony Bankart lesion who were treated with all arthroscopic reduction and internal fixation with metal anchors were included in this study. Among them 40 patients were male and 5 patients were female. The average age at the surgery was 27.6 years (16.5 - 50.1 years). The average duration of follow-up was 29.7 months (24.8 - 49.0 months). A history of recurrent dislocation of affected shoulder was found in all patients. Metal anchors were used to fix the bony Bankart lesion during the surgery. Hill-Sachs remplissage technique was used to treat the Engaging Hill-Sachs lesion. The preoperative American Shoulder and Elbow Society (ASES) score, Constant-Murley score, Rowe score and the VAS score for instability were 84 +/- 14, 95.1 +/- 4.6, 39.4 +/- 2.9 and 5 +/- 3 respectively. RESULTS: No significant change was found regarding active forward elevation, external rotation and internal rotation after the surgery. The ASES score, Constant-Murley score, Rowe score and the VAS score of stability were 95 +/- 7, 98.3 +/- 2.2, 84.5 +/- 22.0 and 1 +/- 2, improved significantly higher after the surgery (P < 0.01). One subluxation and 3 redislocation were happened during follow-up. The overall failure rate was 8.9% (4/45). CONCLUSIONS: All arthroscopic reduction and fixation of bony Bankart lesion can achieve a good result. PMID- 22041674 TI - [Combination with vascular resection and reconstruction in resection of hilar cholangiocarcinoma]. AB - OBJECTIVE: To investigate the value of vascular resection and reconstruction in resection of hilar cholangiocarcinoma. METHODS: The clinical data of 17 patients with hilar cholangiocarcinoma received resection in combination with vascular resection and reconstruction from January 2000 to September 2009 was retrospectively analyzed. Among the 17 patients, 6 underwent portal vein segmental resection and end-to-end anastomosis, 3 underwent portal vein wedge resection, 1 underwent hepatic artery ligature, 2 underwent hepatic artery segmental resection and end-to-end anastomosis, 1 underwent portal vein arterialization, 1 underwent portal vein wedge resection and hepatic artery ligature simultaneously, 2 underwent portal vein segmental resection and hepatic artery segmental resection and end-to-end anastomosis simultaneously, 1 underwent portal vein segmental resection and right hepatic artery and gastroduodenal artery end-to-end anastomosis simultaneously. RESULTS: Four patients died and the mortality was 4/17. Three patients died of renal dysfunction followed with multiple organ dysfunction and 1 patient died of sepsis shock. Among the 13 survive patients, 6 had a smooth postoperative recover and 7 developed complications: 3 had bile leakage, 1 had respiratory failure, 1 had cholangitis due to obstruction of U tube, 1 had abdominal infection and thrombosis in portal vein system and 1 had portal vein stenosis and liver abscess. Follow-up investigation showed that the median survival time was 18 months and four patients still alive. CONCLUSIONS: Combination of vascular resection and reconstruction in the resection of hilar cholangiocarcinoma may help to improve the resection rate but still have a high postoperative risk. The complications of renal dysfunction should be alert during the postoperative observation. The procedure of hepatic arterial reconstruction may help to reduce postoperative morbidity. PMID- 22041675 TI - [Clinical analysis of level V occult metastasis of papillary thyroid carcinoma]. AB - OBJECTIVE: To analyze the occult level V lymph node (LN) metastases in papillary thyroid carcinoma (PTC) with clinical factors. METHODS: The clinical data of 203 PTC patients with clinical positive neck lymph nodes in level II, III and IV based on preoperative ultrasonography, who underwent therapeutic lateral neck dissection (level II-V) between January 2001 and June 2009 were retrospectively reviewed. There were 60 male and 143 female patients in the study. The median age at diagnosis was 42 years (ranging from 16 to 76 years). The 203 patients had undergone ipsilateral thyroidectomy and simultaneously neck dissections (II-VI). All patients had no suspicion of clinical positive neck nodes in level V. Univariate and Multivariate analysis were performed using the Pearson chi-square test and a binary logistic regression test, respectively. RESULTS: The rate of metastatic at levels II, III and IV was 47.3%(96/203), 79.8%(162/203), 81.3% (165/203), respectively. The rate of occult metastatic at level V were observed in 14.3%(29/203). In univariate analysis, LN metastasis in level V was statistically significantly more frequent in patients with positive level IV LNs (chi(2) = 5.651, P = 0.017) and positive LNs throughout the lateral neck (level III+IV) (chi(2) = 10.936, P = 0.001). Multivariate analysis showed that positive LN involvement in all lateral neck (level III+IV) is an independent predictive factor of level V LN metastasis (P = 0.046, OR = 4.550). CONCLUSION: In PTC patients without suspicious LNs in neck level IV by preoperative ultrasound, prophylactic level V LN dissection may be omitted. PMID- 22041676 TI - [Clinical application of redo coronary artery bypass grafting]. AB - OBJECTIVE: To determine the clinical characteristics and outcomes of redo CABG. METHODS: The outcomes of 42 consecutive patients who underwent redo CABG from January 2002 to December 2010 was analyzed. There were 29 males and 13 females, aging from 46 to 78 years old with a mean of (61.2 +/- 2.1) years. Off-pump CABG was applied for 31 patients and on-pump CABG for 11 patients. There were 1 patient underwent concomitant aortic valve replacement and 1 patient underwent aortic root and right aortic arch replacement respectively. RESULTS: Three patients died of right ventricle rupture, heart failure and multiple system organ failure respectively and the perioperative mortality rate was 4.8%. The post operatively mechanical ventilation time varied from 9 to 27 h with a mean of (17 +/- 7) h. There was no residual angina and perioperative myocardial infarction in the remaining patients who were all discharged uneventfully. Intraoperative 6 patients had accepted intraaortic balloon counterpulsation. During the follow-up from 6 months to 4.5 years for 38 patients, which showed no evidence of recurrent angina and postoperative coronary CT angiography in 12 patients showed the patency of grafts is good. CONCLUSION: Satisfactory outcome of redo coronary artery bypass grafting can be achieved if proper indication were choose and reasonable management were performed. PMID- 22041677 TI - [Treatment and prognostic analysis of 1638 patients with non-small cell lung cancer]. AB - OBJECTIVE: To study the prognosis and prognostic factors of non-small-cell lung carcinoma (NSCLC) according the new TNM stage system. METHODS: Clinic data of 1638 inpatient cases admitted from January 2001 to January 2005 were retrospectively reviewed. There were 1083 male and 555 female patients in the study and the average age was 59.5 years. All the patients received surgical procedures. RESULTS: The overall 1, 3, 5-year survival rate was 80.0%, 52.3%, 39.0%. The main prognostic factors were bronchial stump, operation type, T stage, N stage, the number of lymph nodes (LNs) in lymph nodes dissection (1 - 10, 11 - 20, and > 20), overall N stations (< 4 and >= 4) and postoperative radiotherapy (all P < 0.05). Cox regression suggested that T stage (P = 0.000), N stage (P = 0.000), operation type (P = 0.001) and LNs (P = 0.013) were independent factors affecting the prognosis. CONCLUSIONS: The overall survival rate of NSCLC is poor. T stage, N stage, operation type and LNs are independent factors affecting the prognosis. PMID- 22041678 TI - [Treatment of developmental dysplasia of hip by modified Sutherland pelvic osteotomy]. AB - OBJECTIVE: To investigate the clinical results of modified Sutherland pelvic osteotomy for developmental dysplasia of hip (DDH). METHODS: Sutherland pelvic osteotomy were performed in 10 patients (11 hips) with DDH. Among them, there were 3 male (3 hips) and 7 female (8 hips) patients, aged (32 +/- 8) years. During operation, arthroscopes were performed additionally to remove the existing hyperplasia tissue in the fossae ovalis and trimming acetabulum and glenoid labrum, thus to insure the better match between the femoral head and the realigned acetabulum. The change of imaging indexes were acquired by comparing the preoperative X-ray with the postoperative X-ray. The change of hip function and life quality were acknowledged according to contrast and analysis Harris hip score and Short Form 12-items Health Survey (SF-12) before and after osteotomy. RESULTS: All patients were followed up for a mean of (5.2 +/- 2.3) years, the osteotomy were all union in 3 months. The acetabular head index was 71 +/- 8 before operation, and 86 +/- 4 after operation. The pre- and post-operative centre edge angle were (7 +/- 9) degrees and (33 +/- 9) degrees , sharp angle were (48 +/- 4) degrees and (37 +/- 5) degrees , acetabular index angle were (24 +/- 8) degrees and (11 +/- 5) degrees respectively. The average Harris score improved from 42 +/- 13 preoperatively to 90 +/- 5 postoperatively, with 100% excellent and good results. Every domains of SF-12 was improved in the different extents postoperatively, the improvement of physical component summary was more conspicuous than mental component summary. The imaging indexes, Harris and SF-12 were all improved with significant difference (all P < 0.05). CONCLUSIONS: The modified Sutherland pelvic osteotomy is effective. It could increase the load bearing capacity of hip, and improve the quality of life. PMID- 22041679 TI - [Selective thoracic fusion in the scoliosis associated with syringomyelia]. AB - OBJECTIVE: To evaluate the surgical results of selective thoracic fusion (STF) for scoliosis associated with syringomyelia. METHODS: From January 2001 to January 2009, 93 cases of scoliosis associated with syringomyelia were retrospectively reviewed. There were 11 cases who underwent STF and were followed up more than 2 years, which included 8 female and 3 male, the mean age was 14.9 years (9 - 21 years). Curve type, coronal and sagittal Cobb angle, apical vertebral rotation apical vertebral translation, flexibility, trunk shift were recorded and analyzed. RESULTS: There were 9 double curves and 2 triple curves, the Lenke type of thoracolumbar/lumbar curve included Lenke A in 2 cases, Lenke B in 7 cases and Lenke C in 2 cases. The average coronal Cobb angle of thoracic curve before and after surgery were 62.6 degrees and 19.0 degrees respectively, and the average correction rate was 69.6%. The average coronal Cobb angle of thoracolumbar/lumbar curve before and after surgery were 36.1 degrees and 11.6 degrees respectively, and the average spontaneous correction rate was 67.9%. The followed up time ranged from 24 to 48 months (mean 29.5 months), the average loss of correction rate was 6.8%. Only one trunk decompensation was noted at final follow-up. Pedicle screw nut loosening occurred in one patient and this patient underwent revision surgery, no neurological complication was noted at final follow-up. CONCLUSIONS: STF could be safely performed in scoliosis associated with syringomyelia. Thoracolumbar/lumbar curve in these patients has similar spontaneous correction ability compared with idiopathic scoliosis patients. The satisfactory result could be achieved according to the STF criteria for IS. PMID- 22041680 TI - [Expression of chondromodulin-1 in the adult degenerative intervertebral disc]. AB - OBJECTIVES: To investigate the expression of chondromodulin-1 (ChM-I) in human adult degenerative intervertebral disc (IVD) cells and the relationship between ChM-I expression and disc degeneration. METHODS: Three degenerated disc specimens obtained from patients in the treatment of disc degenerative disease from March to April 2009 were used for cell culture. ChM-I expression in IVD cells was examined by RT-PCR and Western blot. The effect of basic fibroblast growth factor (bFGF) on the expression of ChM-I was assessed by real-time PCR and Western blot. From October 2008 to October 2009, 26 human IVD tissues were obtained from patients in the surgical treatment of disc degenerative disease at different stage of degeneration according to MRI. Six IVD tissues removed from patients with metastatic spinal tumor were used as normal control. The expression of ChM-I determined by immunohistochemical analysis was correlated with MRI degeneration grade. RESULTS: RT-PCR and Western blot examination showed that ChM-I was expressed in both adult degenerative anulus fibrosus and nucleus pulposus cells. The mRNA and protein expression of ChM-I were both down-regulated by administration of bFGF with dose-dependent way (P < 0.05). Immunohistochemical analysis showed the percent of ChM-I immunopositive cells in the control group was 0.12 +/- 0.03, and the number increased significantly in the advanced degeneration group (P < 0.05). CONCLUSIONS: The current results demonstrate that IVD cells express ChM-I. Administration of bFGF down-regulates the expression of ChM-I. The expression of ChM-I is correlated with the degree of IVD degeneration which means it may involve in the process of IVD degeneration. PMID- 22041681 TI - [Construction and biological assessment of tissue engineering intervertebral disc]. AB - OBJECTIVE: To investigate the value of bone marrow-mesenchymal stem cells (BM MSCs) transformed by nucleus pulposus (NPs) for construction of tissue engineering disc. METHODS: BM-MSCs and fetal NPs were cultured in vitro, planted on polylactic acid-polyglycolic acid copolymer (PLGA), and observed with inverted microscope and scanning electronic microscope. PLGA scaffolds with adherent BM MSCs and NPs, as well as BM-MSCs and NPs suspension were implanted into intervertebral discs of New Zealand white rabbits, respectively. Intervertebral signal intensity was evaluated by Thompson grading 12 weeks later. Proteoglycan and type IIcollagen were determined by spectrophotometric method and immunohistochemistry, respectively. RESULTS: Spindle or multi-angular BM-MSCs turned into fibro-like phenotype coculture of BM-MSCs and NPs, which grew well with normal morphology when they attached on PLGA scaffolds. There was statistical difference in intervertebral signal intensity, and the expression of proteoglycan and type IIcollagen between PLGA scaffolds group and control group (P < 0.05), the content of proteoglycan was (3.93 +/- 0.31) mg/100 mg in the PLGA scaffolds group whereas (3.52 +/- 0.26) mg/100 mg in the control group. CONCLUSIONS: BM-MSCs can be induced into NPs by cocultivation, and PLGA scaffolds can provide good growing conditions, and maintain high mechanical properties and spacial structure which meet the requirement of tissue engineering disc to prevent degeneration. PMID- 22041682 TI - [Clinical analysis of robotic mitral valve repair]. AB - OBJECTIVE: To determine the safety and efficacy of robotic mitral valve repair using da Vinci S Surgical system. Method From January 2007 to April 2011, over 400 cases of robotic cardiac surgery have been performed, in which 60 patients with isolated mitral valve insufficiency underwent robotic mitral valve repair, including 42 male and 18 female patients with a mean age of (44 +/- 13) years (ranging from 14 to 70 years). Forty-eight patients were in NYHA class I-II and 12 patients in class III. Fourteen patients were concomitant with atrial fibrillation. Surgery approach was achieved through 4 right chest ports with femoral perfusion and Chitwood aortic occlusion. Antegrade cold blood cardioplegia was administered directly via chest for myocardial protection. The transesophageal echocardiography was used intraoperatively to estimate the surgical results. RESULTS: All patients had successful valve repair including quadrangular resections, sliding plasties and chordal replacement. There was no conversion to median sternotomy. The mean cardiopulmonary bypass and arrested heart time were (132 +/- 30) min and (88 +/- 22) min. One patient had hemolysis after operation, and required mitral valve replacement. Echocardiographic follow up revealed trace to mild regurgitation in 2 patients with a mean of (16 +/- 9) months. CONCLUSION: Robotic mitral valve repair is safe and efficacious in the patients with isolated mitral valve insufficiency. PMID- 22041683 TI - [The application of cervical arthroplasty with Mobi-C for treatment of cervical spondylotic radiculopathy]. AB - OBJECTIVE: To investigate the clinical effectiveness of cervical arthroplasty with Mobi-C prosthesis for treatment of cervical spondylotic radiculopathy. METHODS: From March 2008 to November 2009, a group of 67 patients with cervical spondylotic radiculopathy were analyzed retrospectively. The short form-36 physical component summary (SF-36) and visual analogue scale (VAS) score were used to compare clinical outcome pre- and postoperatively. The follow-up was performed at 3 d, 3 months, 6 months and 1 year postoperatively. Static and dynamic radiography were taken to evaluate height of disc space, range of motion (ROM) and heterotopic ossification (HO) of index levels. RESULTS: Fifty-one cases were followed up, 16 cases were lost. Average follow-up was for 19.7 months (13 - 31 months). All of patients had improvement for clinical symptoms. There was a significant difference on SF-36 between pre- and postoperatively. The significant difference was found in VAS score in which neck pain was decreased from preoperative 4.6 +/- 0.4 to postoperative 2.0 +/- 0.5 (P < 0.05), arm pain was decreased from preoperative 6.5 +/- 0.4 to postoperative 1.3 +/- 0.4 (P < 0.05). There was a significant difference in height of disc space which was increased from preoperative (6.5 +/- 1.1) mm to (7.7 +/- 0.9) mm (P < 0.05). ROM was increased from preoperative 7.2 degrees +/- 3.1 degrees to latest follow-up 8.1 degrees +/- 3.2 degrees , however, no significant difference was found concerning ROM pre- and postoperatively (P > 0.05). No other complications were met during follow-up period other than the 17 cases of heterotopic ossification in ClassI, the 7 cases in Class II in 1 year postoperatively, but no any correlation were found between the radiographic finding in HO and clinical symptoms. CONCLUSIONS: Cervical arthroplasty with Mobi-C could improve neurofunctional symptoms, maintain ROM of index level and height of disc space. For accurate patient selection, long term follow-up is still needed in prospective randomized study. PMID- 22041688 TI - Relationship between oxidative stress and cardiomyopathic changes in ovariectomized rats. AB - OBJECTIVES: Menopause has a negative effect on cardiovascular functions. However, very little is known of the overall effect of menopause on the cardiac ultrastructure or the pathophysiological basis of this. METHODS: A group of 12 week-old female Sprague Dawley rats were randomly allocated to healthy control (n = 6) and ovariectomy groups (n = 6). Twelve weeks after ovariectomy, the rats' cardiac tissues were histopathologically analyzed for determination of oxidant and antioxidant enzymes [activities of catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) and amount of glutathione (GSH) and lipid peroxidation (LPO)]. RESULTS: When compared to the control group, the ovariectomy group showed cardiomyopathic changes. In tissue, activities of CAT (185 +/- 2.4 vs. 112 +/- 1.4 mmol/min/mg tissue; p < 0.05), SOD (153 +/- 1.0 vs. 146 +/- 0.7 mmol/min/mg tissue; p < 0.05) and MPO (19 +/- 0.8 vs. 8.6 +/- 0.11 MUmol/min/mg tissue; p < 0.05) and LPO levels (32.1 +/- 0.77 vs. 14.4 +/- 0.20 nmol/g tissue; p < 0.05) were significantly increased in the ovariectomy group when compared to the control group. However, GSH levels (3.43 +/- 0.02 vs. 3.73 +/- 0.01 nmol/g tissue; p < 0.05) were significantly lower in the ovariectomy group when compared to the control group. CONCLUSION: Using an experimental animal model, we were able to demonstrate that menopause causes cardiomyopathic changes, and we propose that these changes could be mediated by oxidative stress. PMID- 22041689 TI - Supramolecular assemblies of dimolybdenum transoids built by Mo2-enhanced perfluorophenyl-perfluorophenyl synthons. AB - Two supramolecular assemblies were developed by the dimmolybdenum paddlewheel complex trans-Mo(2)(DAniF)(2)(O(2)CC(6)F(5))(2) (1) (ancillary ligand DAniF = N,N'-di-(p-anisyl)formamidinate) through intermolecular offset face to face C(6)F(5)...C(6)F(5) interactions. The two networks are different because of the presence and absence of tetrahydrofuran (THF) axial coordination to the Mo(2) units, but feature commonly short interplanar distances between the two paired perfluorophenyl groups, that is, 3.30 A and 3.23 A, respectively, which are similar to the shortest intermolecular C...F contacts between two atoms in meta and ortho positions. Consistently, as indicated by the Mulliken population analysis, the dipole moments for the meta and ortho C-F bonds are considerably enlarged because the pentafluorobenzoate groups are bonded to the dimetal unit. In comparison, X-ray structural and theoretical analyses were also made for the parent molecule pentafluorobenzoic acid. The resultant data show that charge distribution on the perfluorophenyl group has a major influence on the C(6)F(5)...C(6)F(5) binding mode. Therefore, it is evidenced that the dimetal unit plays a role in further polarizing the highly polarized C-F bonds and the intermolecular perfluorophenyl-perfluorophenyl interactions are dominated by the C...F dipole-dipole interaction, rather than aromatic-aromatic pi-pi stacking. PMID- 22041690 TI - [Breast reconstruction with TRAM flap after selective embolization of the deep inferior epigastric artery (series of 69 patients)]. AB - Vascular complications of the unipedicled TRAM flap pointed out the need for solutions to decrease such occurrences. The flap surgical delay before transfer has been advocated to improve the blood supply but, at the same time, it increases the risk of wound infection at the donor site and imposes a general anesthesia. The DIEP and the free TRAM flap are more complex procedures and need heavy structural resources. Preferential use of the ipsilateral muscular pedicle suggests a lower partial flap necrosis rate. Selective embolization of the deep inferior epigastric arteries prior to surgery realizes an alternative delay and brings a decrease in the vascular complication rate as shown in a study of 40 patients by Scheufler in 2000. We present a series of 69 patients who were reconstructed by means of a delayed pedicled TRAM flap with selective embolization and a predominant use of the ispsilateral pedicle. Sonographic studies performed in 48 patients prior to surgery showed no significative difference in the diameter of the superior epigastic arteries, with or without previous radiotherapy. The mean interval between embolization and surgery was 30 days; the embolization was performed bilateraly in five patients (4 %), and unilaterally in 64 patients (96 %). The mean age of patients was 54 years, radiotherapy was applied in 43 patients (62 %), smoking patients: 11 (16 %), obesity: five (7 %). The ispsilateral pedicled was used in 67 patients (97 %), controlateral pedicle in two patients (3 %). Postoperative flap complications were comprised of partial flap necrosis in two cases (2,9 %), fat necrosis in six cases (8,7 %), impaired wound healing in three cases (4,3 %), abdominal wall weakness in two cases (2,9 %). We compared the present study of ispsilateral delayed pedicled flap to a study from the same authors concerning controlateral pedicled flaps without delay. It has been demonstrated that the complications rate of partial necrosis was divided by four in the first study compared to the second. The preoperative selective embolization of the deep inferior epigastric artery in association with the use of ipsilateral pedicule in TRAM flap decrease the complications rate significatively compared to the controlateral pedicled flap in TRAM flaps. PMID- 22041691 TI - [Historical research on cinchona cultivation in Japan]. AB - Cinchona is one of the most important medicinal plants as it contains quinine, a potent medicine for malaria. In this review, I reveal the history of cinchona introduction and cultivation in Japan. Cinchona was first introduced to Japan in 1876 from Java based on the proposal submitted by Takeaki Enomoto to the Meiji government. However, the cultivation attempt ended in failure. Later in 1922, Hoshi Pharmaceutical Co. succeeded for the first time in cultivating cinchona in Taiwan, which was then under Japanese colonial rule, and in manufacturing quinine from the cinchona tree in 1934. This was a historic feat in Japan, completing an entire process from cinchona cultivation to quinine manufacture all within the confines of the country. To commemorate this undertaking, the company dedicated a cinchona log harvested for the first time to the Imperial court. It was revealed that a log of unknown origin, which had been left untouched for years at Hoshi University, was the cinchona log from the time of commemoration. Yasusada Tashiro (1856-1928), who has made a great contribution to cinchona cultivation in Japan for over 50 years, led Hoshi Pharmaceutical Co. to success in cultivation. PMID- 22041692 TI - [Regulation and analysis of intracellular trafficking of nucleic acids based on quantitative and dynamic imaging]. AB - In the 21st century the category of biomedicine is now expanding from low molecular drugs to recombinant proteins, antibodies, and nucleic acids (e.q., siRNA and plasmid DNA). In this era also, development of a novel nanotechnology to control intracellular trafficking is highly desired. For a promising gene therapy, an efficient nuclear delivery vector is a minimum requirement. Quantitative and mechanism-based information on differences in transfection efficiency between viral and non-viral vectors would be highly useful to improve the effectiveness of non-viral vectors. In this review, we will summarize our recent progress in quantitative comparison and underlying mechanisms of the intracellular trafficking between adenovirus vectors and plasmid DNA (pDNA) transfected by non-viral vectors. Our analysis has revealed that poor post nuclear delivery events, as well as the nuclear delivery process itself are key processes to focus on. Especially, less effective transcription and translation are most likely due to poor nuclear decondensation and excess electrostatic interaction between mRNA and the gene carrier, respectively. Meanwhile, we have developed a multi-functional envelope-type nano device (MEND), in which the pDNA/polycation core is encapsulated in the lipid bilayers. Based on feedback information concerning the rate-limiting processes of gene carriers, we controlled the number of lipid envelopes to enhance the decoating of encapsulated pDNA from the envelope structure. As an expanded application of this concept, we have developed a tetra-lamellar MEND (T-MEND), which is designed to overcome the endosome and nuclear membranes by step-wise membrane fusion. PMID- 22041693 TI - [Novel therapeutic approach based on recent understanding of the development of metabolic syndrome]. AB - Obesity is associated with metabolic syndrome, a cluster of symptoms including diabetes, hyperlipidemia, hypertension and arteriosclerosis, which can cause serious health problems. Accumulating evidence suggests that endoplasmic reticulum stress (ER stress) is associated with metabolic syndrome. Leptin is an anti-obesity hormone, which is secreted from adipose tissue. Circulating leptin acts at the brain hypothalamus and reduces food intake. As most forms of obesity indicate a state of leptin resistance, elucidation of the mechanisms of leptin resistance would be an important subject. We and other groups have recently suggested that leptin resistance may be derived from ER stress. These results raised the possibility that attenuating ER stress would be effective treatment for the disease. In the present review article, recent understanding of the mechanisms of the development of obesity and the potential novel therapeutic approaches targeting ER stress are discussed. PMID- 22041694 TI - [Development of domino reactions based on skeletal rearrangement]. AB - Domino reactions, which enable formations of several chemical bonds and multi step transformation in one-pot process, have received much attention as an efficient synthetic methodology to preserve chemists from time-consuming purification protocols and protection-deprotection procedures. Furthermore, the domino processes containing skeletal rearrangement have been utilized for constructions of complex molecules because of their potential that they could afford entirely different valuable structures from readily available simple substrates. We recently developed novel domino reactions including ring enlargement process, which could afford biologically important cyclopentanones and nitrogen heterocycles. In this review, we will describe 1) a novel type of palladium-catalyzed domino insertion-ring expansion reaction of dienylcyclobutanols, which could enable a stereospecific synthesis of (Z)-2-(3 aryl-1-propenyl)cyclopentanones, 2) ruthenium-catalyzed domino ring expansion insertion reaction of 1-acetylenylcyclobutanols for a construction of 2 alkylidenecyclopentanones, and 3) DIBALH-mediated reductive ring expansion reaction of oximes and studies on the reaction mechanisms. The rationales for the observed stereoselectivities in each reaction are also discussed. PMID- 22041695 TI - [Ligand recognition mechanism of lipocalin-type prostaglandin D synthase]. AB - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is a multi functional protein acting as a PGD(2) synthesizing enzyme, a transporter or scavenger of various lipophilic ligands, and an amyloid beta chaperon in the brain. L-PGDS is a member of the lipocalin superfamily and has the ability to bind various lipophilic molecules such as prostanoid, retinoid, bile pigment, and amyloid beta peptide. However, the molecular mechanism for a wide variety of ligand binding has not been well understood. In this study, we determined by NMR the structure of recombinant mouse L-PGDS and L-PGDS/PGH(2) analog complex. L-PGDS has the typical lipocalin fold, consisting of an eight-stranded beta-barrel and a long alpha-helix. The interior of the barrel formed a hydrophobic cavity opening to the upper end of the barrel, the size of which was larger than those of other lipocalins and the cavity contained two pockets. Kinetic studies and molecular docking studies based on the result of NMR titration experiments provide the direct evidence for two binding sites for PGH(2) and retinoic acid in the large cavity of L-PGDS. Structural comparison of L-PGDS/U-46619 complex with apo-L-PGDS showed that the H2-helix, CD-loop, and EF-loop located at the upper end of the beta-barrel change the conformation to cover the entry of the cavity upon U-46619 binding. These results indicated that the two binding sites in the large cavity and induced fit mechanism were responsible for the broad ligand specificity of L PGDS. PMID- 22041696 TI - [Non-invasive drug delivery system with the claudin binder]. AB - The intercellular spaces between adjacent epithelial cells are sealed by tight junctions (TJs). Modulation of TJ-seal is a potent strategy for drug absorption. Claudin is a key structural and functional component of TJ-seal. Claudin comprises a tetra-transmembrane protein family consisting of more than 20 members, whose expression profiles and barrier-function differ among tissues. For instance, claudin-1 plays roles in the epidermal and mucosal barriers, and claudin-4 regulates the mucosal barrier. Claudin forms homo- and hetero-type TJ strands. Properties of TJ-seal are determined by combination of the claudin family members. Some claudin strands work as size-selective or charge-selective paracellular routes for solutes. Thus, claudin modulators will make it possible to deliver drugs in a solute- and tissue-specific manner. The C-terminal fragment of the Clostridium perfringens enterotoxin (C-CPE) is the most characterized claudin modulator. In this review, we describe potency of claudin-targeting mucosal absorption, and we mentioned development of a novel claudin modulator using C-CPE as a prototype. PMID- 22041697 TI - [Genetic polymorphisms of SLCO1B1 for drug pharmacokinetics and its clinical implications]. AB - Various drug transporters are selectively expressed in single or multiple tissues, such as the intestine, liver and kidney, where these transporters play various roles in drug absorption, distribution and excretion. Genetic polymorphisms in drug transporters as well as drug-metabolizing enzymes are associated with interindividual differences in drug disposition, efficacy and toxicity. Organic anion transporting polypeptide 1B1 (OATP1B1, gene SLCO1B1) is expressed on the basolateral membrane of hepatocytes and can facilitate hepatic uptake of certain clinically relevant drugs such as statins except for fluvastatin, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, antidiabetic drug (repaglinide) and anticancer drugs (SN-38 and methotrexate). Some single nucleotide polymorphisms or haplotypes of the SLCO1B1 gene have been identified and demonstrated to have functional significance for transporter activity. For examples, the SLCO1B1*15 haplotype (or 521T>C genotype) results in decreased uptake activity of SN-38 from systemic circulation, leading to increased plasma concentration of SN-38 and an enhanced risk of neutropenia. This review focuses on the impact of genetic polymorphisms of the SLCO1B1 gene on transport activity, and implications for the clinical efficacy and toxicity of clinically useful drugs. PMID- 22041698 TI - [Effect of the active adult learning/patient oriented clerkship on affective reaction of students ~ from the results of student survey]. AB - We have previously reported the efficacy of the Patient Oriented Clerkship (POC) in the clinical clerkship in Showa University Hospitals, by a trial with old four year pharmacy program students. In the unique clerkship, each student has a patient in charge, and follows his/her clinical conditions throughout the rotation. The aim of the POC is that having the students learn spontaneously (Active Learning) and actively (Adult Learning) promoted by student's commitment and responsibility by communicating with patients and health professionals in a team. As the POC requires students both Active Learning and Adult Learning, we define the POC as Active Adult Learning (AAL). Having a patient in charge for each student gives them many opportunities to participate in the medical team and foster their problem solving skills. Our previous study eventually showed positive results of the POC in the one-month short clerkship in the four-year program. On the other hand, the effect of the unique hospital clerkship in the new six-year program is not known. We conducted a student survey to clarify the learning effect in the new six-year education system which was revised and 2.5 month clinical clerkship was scheduled according to the model core clerkship curriculum. This report is the first report to show a challenge of the AAL/POC clerkship in the new six-year pharmacy education program. PMID- 22041699 TI - [Face-to-face questionnaire survey on the use of multiple antipsychotics and the manifestation of side effects in outpatients with schizophrenia]. AB - We investigated the use of multiple antipsychotics and the manifestation of side effects in outpatients with schizophrenia and compared the results of patients who received 1 antipsychotic (monotherapy) with those of patients who received more than 1 antipsychotic (multidrug therapy). To achieve this, we visited 8 community life-support centers and conducted a face-to-face questionnaire survey with 47 outpatients. Sixteen (34%) of these patients had received monotherapy and 31 (66%), multidrug therapy. Complaints involving the central nervous system, anticholinergic symptoms, metabolic symptoms (weight gain, increase in blood glucose, etc.), and extrapyramidal symptoms were seen across the patients. The average incidence of side effects was 2.2 per person in the monotherapy group and 4.8 in the multidrug-therapy group. The number of nonantipsychotic drugs used concomitantly in the monotherapy group was also smaller than that used in the multidrug-therapy group (2.3 and 5.0 per person, respectively). Further, we analyzed the 47 patients as described above; 20 patients received typical antipsychotics (TA group), 10 patients received atypical antipsychotics (AA group), and 17 patients received both typical and atypical antipsychotics (MIX group). The average incidence of side effects in the TA, AA, and MIX groups was 2.8, 3.2, and 5.5 per person, respectively, and the number of nonantipsychotic drugs used concomitantly was 2.2, 3.2, and 6.1, respectively. On the basis of our results, it can be suggested that monotherapy with an atypical antipsychotic can reduce both the number of nonantipsychotic drugs used concomitantly and the average incidence of side effects. PMID- 22041700 TI - Effects of keishibukuryoganryokayokuinin (gui-zhi-fu-ling-wanliao-jia-yiyiren) on the epidermal pigment cells from DBA/2 mice exposed to ultraviolet B (UVB) and/or progesterone. AB - The production of melanin is not only activated by external factors such as sunlight or UV-exposure, but is also considered to be triggered by hormonal factors, particularly sex hormones such as ovarian hormones. Previously, keishibukuryoganryokayokuinin (KBY) was reported to increase the pigmentation and moisture content of dermis in women during the luteal phase of the menstrual cycle, thus suggesting that progesterone could play a critical role in the development of skin pigmentation. In the present study, female DBA/2 mice, a dilute brown strain, were used to examine the effects of KBY on the increase in epidermal pigment cells in mice exposed to ultraviolet B (UVB) radiation or progesterone in an attempt to elucidate its mechanism. An increase in epidermal pigment cells was observed in mice exposed to progesterone. To the best of our knowledge, this is the first study to demonstrate that progesterone causes pigmentation in vivo. Furthermore, administration of KBY to progesterone-exposed mice significantly reduced the number of epidermal pigment cells. However, KBY had no such effects on UVB-induced pigmentation. Another important finding was the gain in body weight in progesterone-exposed mice, while body weight gain was reduced by KBY. The body weight gain was believed to be due to sodium and fluid retention, a kind of adverse effect of progesterone, which may further affect the intracellular pH of melanosomes, which synthesize melanin, in turn, leading to melanin production because tyrosinase activity is linked to the intracellular pH environment. This may help explain the mechanism of the role of KBY in pigmentation. PMID- 22041701 TI - Evaluation of a practical training program for drug information services for fifth-year pharmacy students in a hospital. AB - Drug information (DI) services is an essential resource for pharmacists to provide counseling to patients and guide appropriate medication use. We devised a DI practical training course that incorporated an inquiry-based practical training program and evaluated its effectiveness. A total of 91 fifth-year students in Pharmaceutical Sciences at Fukuoka University took part in the following DI sessions based on specific behavioral objectives (SBOs) for DI in the Model Core Curriculum for Practical Training: inquiry practice, simulated pharmacy and therapeutics committee, DI newsletter, use of emergency and safety information, off-label use in clinical trials, PRE-AVOID (Be prepared to avoid the adverse drug reactions), adverse drug reactions, and small group discussions about drug poisoning. The level of understanding of the SBOs for DI training was >4.2 for each item assessed, and the level of satisfaction for each practice was >3.9. This DI practical training successfully facilitated students' ability to provide DI. The number of students interested in DI services significantly increased (p<0.01). After the DI practical training, many students made statements such as "I realized that DI services is a very important job" and "I feel that pharmacists have much to contribute to DI services by evaluating the most appropriate information from a pharmacist's standpoint." It appears that students recognized the pharmacist's role and importance of DI services in clinical practice through the DI training. These results suggest that this DI practical training program was effective. PMID- 22041702 TI - [Evaluation of the symptoms, adherence and satisfaction after pharmaceutical care at asthma clinic for outpatient]. AB - In the present study, we investigated whether counseling at an outpatient asthma clinic improved asthma symptoms, adherence and patient satisfaction: The asthma control test (ACT) and asthma control questionnaire (ACQ) were used to assess subjective symptoms, 10-item version of the drug attitude inventory (DAI-10) was used to determine medication adherence, and 8-item Japanese version of the client satisfaction questionnaire (CSQ-8J) was used to ascertain patient satisfaction. All scores of inhalation technique, PEF (peak expiratory flow) value/predicted PEF value (%), ACT, ACQ and DAI-10 in 26 patients with asthma increased after counseling at the outpatient asthma clinic compared to those before counseling. The average CSQ-8J score of 28 points (highest possible score: 32 points) indicated that the patients were satisfied with services provided by this clinic. These results indicate that counseling provided by pharmacists at the outpatient clinic is a valuable way improving subjective symptoms, lung function and medication adherence. These results also indicate that counseling at the asthma clinic by pharmacists improves the quality of life of patients with asthma. PMID- 22041703 TI - [Physicopharmaceutical characteristics of ulinastatin vaginal suppositories prepared in a hospital]. AB - We studied a locally applied vaginal preparation (vaginal suppositories) of ulinastatin (urinary trypsin inhibitor, UTI), designed to threatened premature delivery and maintain pregnancy. Witepsol S55 was chosen as the basic component of the vaginal suppositories based on the physical pharmaceutical characteristics of three kinds of hard fats. The average particle size of the UTI aqueous injection was approximately 70% as compared with that of the UTI lyophilized product, used as the base material for the preparation of UTI vaginal suppositories. We compared the physical pharmaceutical properties of UTI vaginal suppositories with water contents of 2.5%, 5.0%, and 7.5%, respectively. Preparation strength negatively correlated with the water content. The coefficient of viscosity positively correlated with the water content of the preparation. UTI vaginal suppositories with a water content of 5.0% had the highest average drug release rate on moment analysis. A comprehensive evaluation of the properties of UTI vaginal suppositories, including high strength due to disintegration resistance, the coefficient of viscosity and its influence on local retention, and drug release and its influence on the duration of effect, indicated that a 5.0% UTI aqueous solution for injection combined with Witepsol S55 as the base was the optimal formulation for the hospital preparation of vaginal suppositories. PMID- 22041704 TI - [Comparison in dissolution behavior of ethical and over-the counter scopolamine butylbromide]. AB - Marketing authorization holders do not disclose any information on the pharmaceutical properties of over-the-counter drugs (OTC). When a drug is switched from a prescription drug to OTC, pharmacists can acquire that information from the corresponding ethical drug (ED) through the package insert, interview form, and so on. However, the pharmaceutical equivalence between ED and OTC is unclear. In this study, we examined the drug dissolution behavior of both ED and OTCs containing scopolamine butylbromide. Dissolution tests were performed by the paddle method using Japanese Pharmacopeia (JP) XV test fluids at pH 1.2, 4.0 and 6.8 and water based on the guidelines for bioequivalence studies of generic products. The dissolution profiles of OTCs differed significantly from ED showing a similarity factor (f2) value ranging from 8.9 to 42.9. Time until 85% dissolution ranged from 23 to 95 min and from 17 to 174 min at pH 1.2 and pH 6.8, respectively. Then JP XV disintegration tests were conducted to investigate differences in the disintegration process. The disintegration time of preparations showing delayed dissolution was prolonged compared to that of others, suggesting that the disintegration of the tablet or capsule is one of the important factors affecting the drug dissolution. These differences in the disintegration and drug dissolution might cause differences in the bioavailability of the drug. For patient safety, more detailed product information of OTCs should be supplied by the manufacturer, and not be assumed from that of corresponding ED. PMID- 22041705 TI - [Antimicrobial activity and frequency of spontaneous gentamicin-resistant mutants in bacteria related skin infections]. AB - Gentamicin is used in an ointment form for the treatment of skin infections. To investigate the effect of gentamicin used as an ointment, the antimicrobial susceptibilities against Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pyogenes, and Pseudomonas aeruginosa isolated from community and medical settings were studied and compared with other antibacterial agents such as fradiomycin, chloramphenicol, and bacitracin used as active ingredient for each ointment. Gentamicin showed antibacterial activities for all standard bacteria tested, but fradiomycin and chloramphenicol showed no such activities for St. pyogenes and P. aeruginosa, respectively. Bacitracin showed activity for St. pyogenes only. The strains of staphylococci isolated from healthy people were highly susceptible to gentamicin, while 49.3% of the isolates from the patients with skin infections were resistant to gentamicin and 96.4% of the gentamicin resistant staphylococci carried the aminoglycoside-resistance gene aacA-aphD. The growths of all strains tested, except for two strains of P. aeruginosa, were inhibited by close below 128 ug/ml of gentamicin. Furthermore, the frequencies of spontaneous mutants resistant to gentamicin, fradiomycin, and chloramphenicol were each investigated using S. aureus, S. epidermidis, St. pyogenes, and P. aeruginosa. At doses of more than 32 ug/ml of gentamicin, no resistant mutants in any of bacteria strains tested were obtained. The concentration of gentamicin on the skin was calculated at approximately 895 ug/ml at least when the commercially used 0.1% gentamicin ointment was applied to the skin. Therefore, our study strongly indicates that the gentamicin ointment used has a potency of sufficiently inhibiting the growth of bacteria, including gentamicin-resistant strains, which cause skin infections in the community. PMID- 22041706 TI - [Induced nausea and vomiting induced by mFOLFOX6 and FOLFIRI with advanced colorectal cancer: a retrospective survey]. AB - Controlling of chemotherapy-induced nausea and vomiting (CINV) is very important for the continuation of chemotherapy, especially for outpatients. CINV can significantly affect a patient's quality of life, leading to poor compliance with further chemotherapy treatment. In this retrospective study, we investigated the incidence of CINV induced by mFOLFOX6 and FOLFIRI in 59 outpatients (32 males and 27 females) with advanced colorectal cancer to evaluate CINV severity using the Common Terminology Criteria for Adverse Events v.3.0. The incidence of nausea in the female group receiving FOLFIRI (grade 1: 66.7% and grade 2: 20.0%) was significantly higher than that in the male group (grade 1: 23.1% and grade 2: 7.7%, p=0.0066). The incidence of nausea in the younger (<63 years old) group receiving FOLFIRI (grade 1: 57.1% and grade 2: 28.6%) was significantly higher than that in the older (?63 years old) group (grade 1: 35.7%, p=0.0031). Multivariable logistic regression analysis indicated that patients who were female or younger had a significantly higher incidence of nausea or vomiting than patients who were male or older, respectively, when treated with FOLFIRI. This suggests that gender (female) and age (younger) are factors predicting poor antiemetic control in outpatients receiving FOLFIRI, but not those treated with mFOLFOX6. Information on such predictive factors should be useful to promote the effectiveness of cancer chemotherapy. PMID- 22041707 TI - [Activation of natural killer T cells by NK-4, a criptocyanine dye]. AB - We previously reported that oral administration of NK-4, a criptocyanine dye, enhances interleukin (IL)-12-depend- ent interferon (IFN)-gamma production by lipopolysaccharide (LPS)-stimulated mouse splenocytes. These findings raised a possibility that NK-4 potentiated IFN-gamma production by T cells, natural killer (NK) cells or natural killer T (NKT) cells in response to IL-12 produced by macrophage and dendritic cells. To explore this possibility, we first analyzed percentages of T, NK or NKT cells in splenocytes of mice that were administered NK-4 orally for three days. The percentage of NKT cells in splenocytes from NK-4 treated mice was significantly (p<0.05) increased compared to vehicle-treated mice. When splenocytes were stimulated with alpha-galactosylceramide (alpha GalCer), an NKT cell ligand, IFN-gamma production by splenocytes from NK-4 treated mice tended to increase, while no difference in the IL-4 production and proliferation were observed between the vehicle- and NK-4-treated mice. When IFN gamma/IL-4 ratios were calculated in individual mice, the ratios were significantly (p<0.05) elevated in NK-4-treated mice. Furthermore, IL-12 production by alpha-GalCer-stimulated splenocytes from NK-4-treated mice was also significantly (p<0.05) increased. These results suggest that oral administration of NK-4 increases the population of type I NKT cells with potent IFN-gamma producing activities. Since IL-12 and IFN-gamma have been shown to play important roles in anti-tumor immunity as well as in the defence against bacterial infection, our results further imply that NK-4 may provide a potential therapeutic tool in cancer immunotherapy. PMID- 22041708 TI - 3D thermoplastic elastomer microfluidic devices for biological probe immobilization. AB - Microfluidics has emerged as a valuable tool for the high-resolution patterning of biological probes on solid supports. Yet, its widespread adoption as a universal biological immobilization tool is still limited by several technical challenges, particularly for the patterning of isolated spots using three dimensional (3D) channel networks. A key limitation arises from the difficulties to adapt the techniques and materials typically used in prototyping to low-cost mass-production. In this paper, we present the fabrication of thin thermoplastic elastomer membranes with microscopic through-holes using a hot-embossing process that is compatible with high-throughput manufacturing. The membranes provide the basis for the fabrication of highly integrated 3D microfluidic devices with a footprint of only 1 * 1 cm(2). When placed on a solid support, the device allows for the immobilization of up to 96 different probes in the form of a 10 * 10 array comprising isolated spots of 50 * 50 MUm(2). The design of the channel network is optimized using 3D simulations based on the Lattice-Boltzmann method to promote capillary action as the sole force distributing the liquid in the device. Finally, we demonstrate the patterning of DNA and protein arrays on hard thermoplastic substrates yielding spots of excellent definition that prove to be highly specific in subsequent hybridization experiments. PMID- 22041709 TI - An organocatalytic approach to enantiomerically enriched alpha-arylcyclohexenones and cyclohexanones. AB - The presence of a p-nitrophenyl group converts acetone into an excellent and versatile nucleophile in organocatalytic processes, able to react with alpha,beta unsaturated aldehydes affording beta-substituted alpha-arylcyclohexenones via a Michael reaction/aldol reaction/dehydration sequence, which occurs in good yields, ee up to 96% and complete diastereoselectivity. The resulting compounds are excellent synthons for the diastereoselective preparation of a variety of synthetically useful polysubstituted cyclohexanones and derivatives. PMID- 22041710 TI - Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. AB - Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors of the adrenal glands and the sympathetic and parasympathetic paraganglia. They can occur sporadically or as a part of different hereditary tumor syndromes. About 30% of PCCs and PGLs are currently believed to be caused by germline mutations and several novel susceptibility genes have recently been discovered. The clinical presentation, including localization, malignant potential, and age of onset, varies depending on the genetic background of the tumors. By reviewing more than 1700 reported cases of hereditary PCC and PGL, a thorough summary of the genetics and clinical features of these tumors is given, both as part of the classical syndromes such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau disease, neurofibromatosis type 1, and succinate dehydrogenase related PCC-PGL and within syndromes associated with a smaller fraction of PCCs/PGLs, such as Carney triad, Carney-Stratakis syndrome, and MEN1. The review also covers the most recently discovered susceptibility genes including KIF1Bbeta, EGLN1/PHD2, SDHAF2, TMEM127, SDHA, and MAX, as well as a comparison with the sporadic form. Further, the latest advances in elucidating the cellular pathways involved in PCC and PGL development are discussed in detail. Finally, an algorithm for genetic testing in patients with PCC and PGL is proposed. PMID- 22041712 TI - Iron-catalysed, hydride-mediated reductive cross-coupling of vinyl halides and Grignard reagents. AB - An iron-catalysed, hydride-mediated reductive cross-coupling reaction has been developed for the preparation of alkanes. Using a bench-stable iron(II) pre catalyst, reductive cross-coupling of vinyl iodides, bromides and chlorides with aryl- and alkyl Grignard reagents successfully gave the products of formal sp(3) sp(3) cross-coupling reactions. PMID- 22041711 TI - Regulation of beta-adrenergic receptor function: an emphasis on receptor resensitization. AB - G protein-coupled receptors are the largest family of cell surface receptors regulating multiple cellular processes. beta-adrenergic receptor (betaAR) is a prototypical member of GPCR family and has been one of the most well studied receptors in determining regulation of receptor function. Agonist activation of betaAR leads to conformational change resulting in coupling to G protein generating cAMP as secondary messenger. The activated betaAR is phosphorylated resulting in binding of beta-arrestin that physically interdicts further G protein coupling leading to receptor desensitization. The phosphorylated betaAR is internalized and undergoes resensitization by dephosphorylation mediated by protein phosphatase 2A in the early endosomes. Although desensitization and resensitization are two sides of the same coin maintaining the homeostatic functioning of the receptor, significant interest has revolved around understanding mechanisms of receptor desensitization while little is known about resensitization. In our current review we provide an overview on regulation of betaAR function with a special emphasis on receptor resensitization and its functional relevance in the context of fine tuning receptor signaling. PMID- 22041713 TI - Inhibition of X-linked inhibitor of apoptosis with embelin differentially affects male versus female behavioral outcome following neonatal hypoxia-ischemia in rats. AB - Hypoxia-ischemia (HI; concurrent oxygen/blood deficiency) and associated encephalopathy represent a common cause of neurological injury in premature/low birth-weight infants and term infants with birth complications. Resulting behavioral impairments include cognitive and/or sensory processing deficits, as well as language disabilities, and clinical evidence shows that male infants with HI exhibit more severe cognitive deficits compared to females with equivalent injury. Evidence also demonstrates activation of sex-dependent apoptotic pathways following HI events, with males preferentially activating a caspase-independent cascade of cell death and females preferentially activating a caspase-dependent cascade following neonatal hypoxic and/or ischemic insults. Based on these combined data, the 'female protection' following HI injury may reflect the endogenous X-linked inhibitor of apoptosis (XIAP), which effectively binds effector caspases and halts downstream cleavage of effector caspases (thus reducing cell death). To test this theory, the current study utilized neonatal injections of vehicle or embelin (a small molecule inhibitor of XIAP) in male and female rats with or without induced HI injury on postnatal day 7 (P7). Subsequent behavioral testing using a clinically relevant task revealed that the inhibition of XIAP exacerbated HI-induced persistent behavioral deficits in females, with no effect on HI males. These results support sex differences in mechanisms of cell death following early HI injuries, and suggest a potential clinical benefit from the development of sex-specific neuroprotectants for the treatment of HI. PMID- 22041714 TI - Distraction arthrodesis with intramedullary nail and mixed bone grafting after failed infected total knee arthroplasty. AB - PURPOSE: The purpose of this study was to determine the success rate of the distraction arthrodesis, which was attempted to maintain the limb length during arthrodesis using an intramedullary nail and mixed bone grafting, in terms of the eradication of infection, solid union, and functional outcome. The hypothesis was that distraction arthrodesis would be successful in union and elimination of infection with minimal limb shortening and a satisfactory functional outcome despite large bone defects. METHODS: Eight patients were managed by arthrodesis using a Huckstep intramedullary nail and massive corticocancellous bone chip grafts from autologous iliac bone and deep-frozen femoral head allografts were included in the study. The mean age of the patients was 65.5 +/- 7.1 years, and the follow-up duration was 52.1 +/- 21.3 months. A mean of 5.3 +/- 1.3 surgical procedures had been performed before arthrodesis. The mean longest and shortest distances of the bone defect were 58.6 +/- 10.3 and 34.6 +/- 7.0 mm, respectively. RESULTS: Radiological union was obtained in all cases at a mean of 9.9 +/- 1.9 months. The mean postoperative limb shortening was 11.0 +/- 7.3 mm when compared to the contralateral knee. The mean Knee Society score was 59.9 +/- 9.2, and the function score was 38.8 +/- 13.3. No additional procedures were required for any of the patients. CONCLUSION: Distraction arthrodesis of infected knees following total knee arthroplasty demonstrated union and eradication of infection in all patients and a large tibiofemoral gap due to the severe bone defect could be managed with massive bone chip grafts. This method of arthrodesis would be a reliable and an effective method for failed total knee arthroplasty when two-staged reimplantation fails or is not attainable. PMID- 22041715 TI - Alteration in skin sensation following knee arthroplasty and its impact on kneeling ability: a comparison of three common surgical incisions. AB - PURPOSE: Disturbance in skin sensation is a recognised, often unpleasant consequence of knee replacement for many patients and may affect function especially kneeling. The aim of this study was to compare post-operative changes in skin sensation following total (TKA) and unicompartmental knee (UKA) arthroplasties using three different incision types and its effect on kneeling ability. METHODS: Skin sensation was recorded using a purpose-designed grid over the front of the knee in 72 patients (78 knees) following knee arthroplasty. Surface area of sensory change, length of incision, and kneeling ability were recorded and compared between three different types of incision; long antero medial and midline for TKA, and short medial for UKA. RESULTS: The average length of the long antero-medial incision was 19 +/- 5 cm with an average area of sensory alteration of 88 +/- 56 cm(2). The average length of the midline incision was 18 +/- 3 cm with an average area of sensory alteration of 57 +/- 52 cm(2). The short medial incision used for UKA averaged 11 +/- 3 cm in length with an average area of sensory alteration of 54 +/- 45 cm(2). Long antero-medial produced a significantly greater area of sensory alteration than standard short medial (P = 0.017), but not the midline incision. There was a significant positive correlation of incision length with reduced sensation. Patients unable to kneel demonstrated a significantly larger area of hypersensitivity than patients who could kneel (P = 0.002). CONCLUSIONS: Increased length of incision results in a greater surface area of sensory change in the front of the knee. This finding was greatest in the long antero-medial incisions used in TKA. The inability to kneel following knee arthroplasty is associated with increased area of hypersensitivity of the anterior knee. LEVEL OF EVIDENCE: Prospective comparative study, Level II. PMID- 22041716 TI - Internal tibial rotation during in vivo, dynamic activity induces greater sliding of tibio-femoral joint contact on the medial compartment. AB - PURPOSE: Although extensive research has been conducted on rotational kinematics, the internal/external rotation of the tibio-femoral joint is perhaps less important for protecting joint health than its effect on joint contact mechanics. The purpose of this study was to evaluate tibio-femoral joint contact paths during a functional activity (running) and investigate the relationship between these arthrokinematic measures and traditional kinematics (internal/external rotation). METHODS: Tibio-femoral motion was assessed for the contralateral (uninjured) knees of 29 ACL-reconstructed individuals during downhill running, using dynamic stereo X-ray combined with three-dimensional CT bone models to produce knee kinematics and dynamic joint contact paths. The joint contact sliding length was estimated by comparing femoral and tibial contact paths. The difference in sliding length between compartments was compared to knee rotation. RESULTS: Sliding length was significantly larger on the medial side (10.2 +/- 3.8 mm) than the lateral side (2.3 +/- 4.0 mm). The difference in sliding length between compartments (mean 7.8 +/- 3.0 mm) was significantly correlated with internal tibial rotation (P < 0.01, R (2) = 0.74). CONCLUSION: The relationship between rotational knee kinematics and joint contact paths was specifically revealed as greater tibial internal rotation was associated with larger magnitude of sliding motion in the medial compartment. This could suggest that lateral pivot movement occurs during running. CLINICAL RELEVANCE: Rotational kinematics abnormality should be treated for restoring normal balance of joint sliding between medial and lateral compartments and preventing future osteoarthritis. LEVEL OF EVIDENCE: Prognostic studies, Level II. PMID- 22041717 TI - Second-generation arthroscopic autologous chondrocyte implantation for the treatment of degenerative cartilage lesions. AB - PURPOSE: Degenerative cartilage lesions present a negative joint environment, which may have a negative effect on the process of cartilage regeneration. The aim of this study is to analyze the clinical outcome obtained with the treatment for isolated degenerative knee cartilage lesions by second-generation arthroscopic autologous chondrocyte implantation (ACI). METHODS: Fifty-eight consecutive patients affected by focal degenerative chondral lesions of the femoral condyles and trochlea were treated by second-generation arthroscopic ACI. The mean age at surgery was 34.7 +/- 9.1 years and the average defect size was 2.3 +/- 0.9 cm(2). The patients were prospectively evaluated with IKDC, EQ-VAS, and Tegner scores preoperatively, at 2 and 6 years. RESULTS: A statistically significant improvement was observed in all scores from the basal evaluation to the final follow-up. The IKDC subjective score improved from 39.3 +/- 13.6 to 68.8 +/- 22.7 and 68.5 +/- 23.9 at the 2- and 6-year follow-ups, respectively, with a significant improvement (P < 0.0005) and stable results over time; the same trend was confirmed by the EQ-VAS and Tegner scores. The worst results were found in patients with a low physical activity level, women, and those having undergone previous surgery, whereas the symptom duration before surgery did not influence the final outcome. The failure rate was 18.5%. CONCLUSIONS: Despite a significant improvement, the results were lower with respect to the outcome reported in different study populations, and the number of failures was markedly higher, too. Tissue-engineered cartilage implantation is a promising approach for the treatment of degenerative chondral lesions, but graft properties, besides mechanical and biochemical joint environment, have to be improved. LEVEL OF EVIDENCE: Case series, Level IV. PMID- 22041718 TI - Caenorhabditis elegans as a chemical screening tool for the study o f neuromuscular disorders. Manual and semi-automated methods. AB - We previously reported the use of the cheap and fast-growing nematode Caenorhabditis elegans to search for molecules, which reduce muscle degeneration in a model for Duchenne Muscular Dystrophy (DMD). We showed that Prednisone, a steroid that is generally prescribed as a palliative treatment to DMD patients, also reduced muscle degeneration in the C. elegans DMD model. We further showed that this strategy could lead to the discovery of new and unsuspected small molecules, which have been further validated in a mammalian model of DMD, i.e. the mdx mouse model. These proof-of-principles demonstrate that C. elegans can serve as a screening tool to search for drugs against neuromuscular disorders. Here, we report and discuss two methodologies used to screen chemical libraries for drugs against muscle disorders in C. elegans. We first describe a manual method used to find drugs against DMD. We further present a semi-automated method, which is currently in use for the search of drugs against the Schwartz Jampel Syndrome (SJS). Both assays are simple to implement and can be readily transposed and/or adapted to screens against other muscle/neuromuscular diseases, which can be modeled in the worm. Finally we discuss, with respect to our experience and knowledge, the different parameters that have to be taken into account before choosing one or the other method. PMID- 22041719 TI - GPCR stabilization using the bicelle-like architecture of mixed sterol-detergent micelles. AB - The biophysical characterization of purified membrane proteins typically requires detergent mediated extraction from native lipid membrane environments. In the case of human G protein-coupled receptors (GPCRs), this process has been complicated by their conformational heterogeneity and the general lack of understanding the composition and interactions within the diverse human cellular membrane environment. Several successful GPCR structure determination efforts have shown that the addition of cholesterol analogs is often critical for maintaining protein stability. We have identified sterols that substantially increase the stability of the NOP receptor (ORL-1), a member of the opioid GPCR family, in a mixed micelle environment. Using dynamic light scattering and small angle X-ray scattering, we have determined that the most thermal stabilizing sterol, cholesteryl hemisuccinate, induces the formation of a bicelle-like micelle architecture when mixed with dodecyl maltoside detergent. Together with mutagenesis studies and recent GPCR structures, our results provide indications that stabilization is attained through a combination of specific sterol binding to GPCRs and modulation of micelle morphology. PMID- 22041720 TI - Translating the WHO Framework Convention on Tobacco Control (FCTC): can we use tobacco control as a model for other non-communicable disease control? AB - Tobacco use is the single most preventable cause of death in the world today. Unchecked, tobacco-related deaths will increase to more than eight million per year by 2030. Galvanized by the seriousness of the threat, the Member States of the World Health Organization (WHO) negotiated the WHO Framework Convention on Tobacco Control (WHO FCTC), which entered into force in 2005. The treaty has enjoyed tremendous global success, with more than 170 Parties, and is often called the most powerful tool in the fight against tobacco-related morbidity and mortality. As the world undergoes the long-predicted transition from communicable to noncommunicable diseases (NCDs) posing the greater health burden, seminal ideas, processes, and outcomes like the WHO FCTC can be used to inform decision making and policy-making. To help begin such knowledge transfer, this paper first examines how tobacco control evolved to become a reasonable, politically feasible topic for treating in the highly globalized context of public health and NCDs. Next, some of the key achievements and challenges that have occurred over the past six years of WHO FCTC implementation are discussed. Finally, a consideration of how some of the successes and lessons learned in tobacco control appear in other NCD contexts is presented. PMID- 22041721 TI - Celebrating 45 years of postgraduate medical education. AB - We are delighted to be celebrating 45 years of publication of the British Journal of Hospital Medicine. The first issue was published in October 1966 (see right) and its introductory editorial is reproduced on p. 546-7. Here we have some brief thoughts from Professor John Blandy, one of the original members of the editorial board, from Mark Allen, the publisher who took the journal over from its previous publishers Thomson in 1985, and from Professor Rob Miller and Rebecca Linssen, the current Editor-in-Chief and Editor. PMID- 22041722 TI - Patient safety: culture eats strategy for breakfast. AB - 'One morning recently, a professor conducted a ward round on an elderly medicine ward in a London teaching hospital. The entourage stopped at an 82-year-old man's bed. The elderly patient was confused and so, unfortunately, was the junior doctor who presented the case. PMID- 22041724 TI - Otitis externa: a clinical review. AB - This article provides a clinical overview of otitis externa, focusing on clinical aspects of the aetiology, diagnosis and management of this important and debilitating condition. PMID- 22041725 TI - Carotid body tumours. AB - Carotid body tumours are a rare class of paraganglionoma arising from the upper neck, but should be considered in the differential diagnosis of neck lumps. A wrong diagnosis of cervical lymphadenopathy followed by excision biopsy may have serious consequences. The only way to minimize such risk is to be aware of their existence. PMID- 22041726 TI - Use of coblation in otolaryngology, head and neck surgery. AB - Coblation is a relatively new, low-temperature electrosurgery technique that has established its place in various surgical fields. This article summarizes the published work on the use of coblation in the field of otorhinolaryngology. PMID- 22041727 TI - Management of the hyperthermic patient. AB - Undifferentiated body temperature of greater than 38 degreesC can herald a number of important clinical syndromes essential to diagnose besides just infectious aetiologies. This review examines the pathophysiology, clinical features and approach to the management of hyperthermia that will lead to appropriate diagnosis and treatment. PMID- 22041728 TI - Preventing fractures in the elderly. AB - Fractures in the elderly are devastating, causing premature death and compromised independence among survivors. With demographic changes, their occurrence is expected to double. Given their crippling consequences, the identification and treatment of osteoporosis and prevention of falls are priorities. PMID- 22041729 TI - Disproportionate elevation of jugular venous pressure in pleural effusion. AB - Constrictive pericarditis is characterized by elevation in jugular venous pressure disproportionate to the severity of concurrent breathlessness. As pleural effusion may be an associated feature it is recommended that jugular venous pressure should be documented in all patients who present with pleural effusion. PMID- 22041730 TI - Online generic induction for doctors in training: an end to repetition? AB - Multi-professional collaboration across the West Midlands has developed an online generic induction package consisting of 18 statutory, mandatory and general modules. The material incorporates best practises in e-learning, including an assessment component. PMID- 22041731 TI - Sporadic Creutzfeldt-Jakob disease presenting as a stroke mimic590. AB - Creutzfeldt-Jakob disease is a rare neurodegenerative disease in which there is an abnormal accumulation of prion protein. It occurs with an incidence of approximately 1 per million per year. Sporadic Creutzfeldt-Jakob disease occurs in approximately 85% of cases, with familial, variant and iatrogenic forms less common. Typically sporadic Creutzfeldt-Jakob disease presents with a rapidly progressive dementia, but sub-variants include the Heidenhain and Oppenheimer Brownell variants. The former presents with visual disturbance and the latter with ataxia. This article describes a 75-year-old man with a Heidenhain variant of sporadic Creutzfeldt-Jakob disease who presented with a sudden onset of homonymous hemianopia mimicking a stroke. PMID- 22041732 TI - A rare cause of haematemesis and chest pain. AB - This article discusses an elderly woman presenting with haematemesis and chest pain who underwent urgent oesophago-gastroduodenoscopy. This revealed a large dissecting intramural oesophageal haematoma, initially mistaken for a varix. This is a rare cause of haematemesis and chest pain but has characteristic endoscopic findings. It is a benign condition that may be managed conservatively and both clinicians and endoscopists should be aware of its classical presentation. Misdiagnosis of the chest pain as cardiac ischaemia may have an adverse outcome if antiplatelet or anticoagulation therapy is commenced. Follow up endoscopy a week later showed complete resolution of the lesion leaving a linear mucosal defect. PMID- 22041733 TI - Parkinson's tremor mimicking torsades de pointes. AB - A 72-year-old woman with Parkinson's disease presented to outpatients with a history of falls. The falls were not associated with loss of consciousness, and the history suggested gait and balance problems leading to falls. A 12-lead electrocardiogram, as shown in Figure 1, had the appearance of torsades de pointes. However, the patient was cardiologically asymptomatic, and the electrocardiogram appearance was thought to be caused by a Parkinson's disease associated artefact. PMID- 22041734 TI - Paraganglioma mimicking adrenal incidentaloma. AB - Paragangliomas can be confused with adrenal incidentalomas because of their proximity to the adrenal glands. A 71-year-old man presented with left-sided abdominal pain. A computed tomography scan showed a large cystic mass with a solid component arising from the left adrenal gland (Figure 1). PMID- 22041735 TI - Matthew Baillie: pioneer of systematic pathology. AB - This year is the 250th anniversary of the birth of Matthew Baillie, whose textbook Morbid Anatomy of the Human Body, published in 1793, and its accompanying atlas, published 6 years later, constituted the first textbook which dealt exclusively with system-based pathology. This adopted a new and convenient method of describing pathology according to the organs involved rather than according to symptoms, as Giovanni Morgagni (1682-1771) of Padua had adopted in his De Sedibus et Causis Morborum (On the sites and causes of disease). This, published in 1760, was rightly regarded as the first textbook which correlated symptoms in life with the appearance of the viscera at autopsy. PMID- 22041737 TI - Protect your most important asset: yourself. AB - You have worked hard to get to where you are today, so it would be foolish to risk it all by not ensuring your income and your assets are protected. Cars, homes and valuables are among the first things we insure, but many people forget about protecting the most valuable asset we have - our income. PMID- 22041739 TI - Should sevoflurane be used for maintenance of anaesthesia in children? AB - Sevoflurane is used for inhalational induction of anaesthesia because of its pleasant odour and quick onset. However, its use for maintenance of anaesthesia in children has been questioned because of the risk of emergence delirium. Emergence delirium is defined by Sikich and Lerman (2004) as a disturbance in awareness of, and attention to, the environment with disorientation and perceptual alterations including hypersensitivity to stimuli and hyperactive motor behaviour in the immediate post-anaesthesia period. Its incidence is between 10 and 80% following general anaesthesia, and it has the potential to cause injury to the child or care provider, may cause intravenous lines or drains to become dislodged, often requires additional nursing support and delays recovery time (Vlajkovic and Sindjelic, 2007). PMID- 22041740 TI - Public health and clinical importance of amoebiasis in Malaysia: a review. AB - Entamoeba histolytica, the causative agent of human amoebiasis remains a significant cause of morbidity and mortality in developing countries and is responsible for up to 100,000 deaths worldwide each year. Entamoeba dispar, morphologically indistinguishable from E. histolytica is more common in humans in many parts of the world. Similarly Entamoeba moshkovskii, which was long considered to be a free-living amoeba is also morphologically identical to E. histolytica and E. dispar, and is highly prevalent in some E. histolytica endemic countries. Humans are the host of infection and there would not appear to be other meaningful animal reservoirs of E. histolytica. Entamoeba. histolytica can be present in sewage and contaminated water. The infection is mainly transmitted via ingestion of water or food contaminated by faeces containing E. histolytica cysts. Clinical features of amoebiasis range from asymptomatic colonization to amoebic dysentery and invasive extraintestinal amoebiasis, which is manifested most commonly in the form of abscesses in liver and lungs. The epidemiology of amoebiasis has dramatically changed since the separation of E. histolytica and E. dispar species and the worldwide prevalence of these species has not been estimated until recently. Morever, E. moshkovskii, another morphologically indistinguishable human parasitic Entamoeba was not mentioned or considered as a contributor to the prevalence figures in endemic areas. Amoebiasis is still a major health problem especially in aboriginal settlements and amongst people living in remote area in Malaysia. However, until now there is only one data currently available to indicate the true prevalence and incidence of E. histolytica and E. dispar. Further studies are needed to determine the burden of E. histolytica, E. dispar and E. moshkovskii infections in Malaysia. In the present review, we briefly summarize all methods use in diagnosing Entamoeba species, ranging from microscopic identification to molecular detection such as culture and isoenzyme analysis, antibody detection tests, antigen detection tests, immunochromatographic assays, conventional PCR, real-time PCR and loop mediated isothermal amplification (LAMP). PMID- 22041741 TI - Antigenic profile of Blomia tropicalis, Aleuroglyphus ovatus and Glycycometus malaysiensis. AB - House dust mites and storage mites are well-known causes for allergenic diseases. The aim of this study was to investigate the immunogenic sites of Blomia tropicalis, Aleurogyphus ovatus and Glycycometus malaysiensis. The mites were maintained in a culture medium at 25oC and 75% relative humidity. Mites were harvested either with heat escape or floatation method, purified, homogenized, quantified and used for the production of polyclonal antibody and immunostaining. For each species of mites, five male mice and five male rats were randomly selected and immunized intraperitoneally with respective crude mite extract at two-weekly intervals. Blomia tropicalis, A. ovatus or G. malaysiensis whole mites and paraffin-embedded mite sections were immunostained with the respective polyclonal antibody. The faecal pellets of mites were intensely stained for all the three species in the present study. The legs of sectioned A. ovatus were not immunogenic as compared with those of G. malaysiensis and B. tropicalis. The outer layer (cuticle) of whole mites and the eggs for these species were very immunogenic. Hence, the polyclonal antibodies obtained in this study may serve as potential tools in detecting the eggs and immature mites in environmental samples. Future studies should focus on the antigenic components of eggs since they were relatively abundant in dust and highly antigenic as seen in the present study. PMID- 22041742 TI - Aedes larval population dynamics and risk for dengue epidemics in Malaysia. AB - Early detection of a dengue outbreak is an important first step towards implementing effective dengue interventions resulting in reduced mortality and morbidity. A dengue mathematical model would be useful for the prediction of an outbreak and evaluation of control measures. However, such a model must be carefully parameterized and validated with epidemiological, ecological and entomological data. A field study was conducted to collect and analyse various parameters to model dengue transmission and outbreak. Dengue prone areas in Kuala Lumpur, Pahang, Kedah and Johor were chosen for this study. Ovitraps were placed outdoor and used to determine the effects of meteorological parameters on vector breeding. Vector population in each area was monitored weekly for 87 weeks. Weather stations, consisting of a temperature and relative humidity data logger and an automated rain gauge, were installed at key locations in each study site. Correlation and Autoregressive Distributed Lag (ADL) model were used to study the relationship among the variables. Previous week rainfall plays a significant role in increasing the mosquito population, followed by maximum humidity and temperature. The secondary data of rainfall, temperature and humidity provided by the meteorological department showed an insignificant relationship with the mosquito population compared to the primary data recorded by the researchers. A well fit model was obtained for each locality to be used as a predictive model to foretell possible outbreak. PMID- 22041743 TI - The effect of Piper aduncum Linn. (Family: Piperaceae) essential oil as aerosol spray against Aedes aegypti (L.) and Aedes albopictus Skuse. AB - The bioefficacy of Piper aduncum L. essential oil formulated in aerosol cans was evaluated against Aedes aegypti and Aedes albopictus in a simulated room. The aerosol spray test was based on the Malaysian test standard for aerosol (MS 1221:1991UDC 632.982.2 modified from WHO 2009 methodology) and examined the knockdown effect within 20 minutes of exposure. Mortality rate after 24 hour of holding period was also determined. A commercial aerosol spray (0.09% prallethrin 0.05% d-phenothrin) was also tested as a comparison. Our results showed that the knockdown effect of the commercial aerosol spray and P. aduncum essential oil spray (8% and 10% concentrations) was significantly higher in Ae. albopictus adult females, when compared with that of Ae. aegypti adult females (P<0.05). There was a significant difference in knockdown between commercial aerosol spray and essential oil spray for both Aedes spp. (P<0.05). The essential oil induced significantly higher mortality in Ae. aegypti (80%) than in Ae. albopictus (71.6%) (P<0.05). The commercial aerosol spray caused 97.7% and 86.5% mortality against Ae. aegypti and Ae. albopictus respectively (P<0.05). Based on these data, P. aduncum essential oil has the potential to be used as an aerosol spray against Aedes spp. PMID- 22041744 TI - Morphometric and meristic characterization of Phlebotomus argentipes species complex in northern Sri Lanka: evidence for the presence of potential leishmaniasis vectors in the country. AB - The transmission of cutaneous leishmaniasis (CL) is of public health concern in Sri Lanka. The parasite Leishmania donovani is reported to be the causative agent for CL in Sri Lanka. However there is no report on the vector of CL in the country. Phlebotomus argentipes sensu lato is the well known vector of L. donovani which causes visceral leishmaniasis (VL) in the nearby South India. The taxon Ph. argentipes previously reported to occur as a species complex comprising of two morphospecies namely A and B. The taxonomy of the Argentipes complex was reassessed recently and reported to have three species viz. Phlebotomus glaucus, Ph. argentipes sensu stricto and Ph. annandalei. A study was carried out in Jaffna mainland, where three CL patients have been recorded, and two associated islands in northern Sri Lanka to record the presence of the members of the Argentipes complex. Sandflies were collected using human landing and cattle baited collections. Collected samples were analyzed based on reported morphometric and meristic characteristics. The study revealed the presence of all three members of the complex in which Ph. glaucus and Ph. argentipes s.s. are reported for the first time in Sri Lanka. PMID- 22041745 TI - Identification of local clinical Candida isolates using CHROMagar CandidaTM as a primary identification method for various Candida species. AB - The objective of our study was to study the effectiveness of CHROMagar CandidaTM as the primary identification method for various clinical Candida isolates, other than the three suggested species by the manufacturer. We studied 34 clinical isolates which were isolated from patients in a local teaching hospital and 7 ATCC strains. These strains were first cultured in Sabouraud dextrose broth (SDB) for 36 hours at 35oC, then on CHROMagar plates at 30oC, 35oC and 37oC. The sensitivity of this agar to identify Candida albicans, Candida dubliniensis, Candida tropicalis, Candida glabrata, Candida rugosa, Candida krusei and Candida parapsilosis ranged between 25 and 100% at 30oC, 14% and 100% at 35oC, 56% and 100% at 37oC. The specificity of this agar was 100% at 30oC, between 97% and 100% at 35oC, 92% and 100% at 37oC. The efficiency of this agar ranged between 88 and 100% at 30oC, 83% and 100% at 35oC, 88% and 100% at 37oC. Each species also gave rise to a variety of colony colours ranging from pink to green to blue of different colony characteristics. Therefore, the chromogenic agar was found to be useful in our study for identifying clinical Candida isolates. PMID- 22041746 TI - Scanning electron micrographs of medically important dust mite, Suidasia pontifica (Acari: Astigmata: Saproglyphidae) in Malaysia. AB - Scanning electron microscope (SEM) images of dust mites, Suidasia pontifica, is presented to provide an improved visualization of the taxonomic characters of these mites. Suidasia pontifica can easily be identified by its scale-like cuticle, presence of external vertical setae (ve), longer external scapular setae (sce) compared to internal scapular setae (sci) and 3 ventral spines on apex of tarsus I. The differences in morphology of male and female S. pontifica are also discussed. PMID- 22041747 TI - Tegumental alterations of Fasciola gigantica due to in vitro treatment with Ro 354. AB - Triclabendazole is the drug of choice against Fasciola infections in humans and animals. However, parasite resistance against triclabendazole is spreading in veterinary field, and there are no drugs of comparable activity currently available for the treatment and control of fascioliasis. The efficacy of a new rhodanine derivative Ro-354 against adult Fasciola gigantica in vitro was investigated. One hour post incubation, scanning and transmission electron microscopic examination revealed an evident disruption of the tegument of F. gigantica as blebbing, swelling and furrowing. Moreover, an increase in severity of tegumental damage as sloughing and absence of spines was observed. In conclusion, Ro-354 shows potent activity against F. gigantica in vitro, and, the authors recommend carrying out more studies to detect its efficacy in vivo. PMID- 22041748 TI - Protective efficacy of Anopheles minimus CYP6P7 and CYP6AA3 against cytotoxicity of pyrethroid insecticides in Spodoptera frugiperda (Sf9) insect cells. AB - Cytochrome P450 monooxygenases (P450s) are enzymes known to metabolize a wide variety of compounds including insecticides. Their overexpression leading to enhanced insecticide detoxification could result in insecticide resistance in insects. The increased mRNA expression of two P450 genes, CYP6P7 and CYP6AA3, has been previously observed in laboratory-selected deltamethrin-resistant Anopheles minimus, a major malaria vector in Southeast Asia, suggesting their role in detoxification of pyrethroids. In this study CYP6P7 and CYP6AA3 were expressed in insect Spodoptera frugiperda (Sf9) cells via baculovirusdirected expression system. Insecticide detoxification capabilities of Sf9 cells with and without expression of CYP6P7 or CYP6AA3 were evaluated using 3-(4,5-dimethyl thiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The results revealed that CYP6P7- or CYP6AA3-expressing cells showed significantly higher cytoprotective capability than parental Sf9 cells against cytotoxicity of pyrethroids including permethrin, cypermethrin and deltamethrin. Such cytoprotective effect was not observed for bioallethrin (pyrethroid), chlorpyrifos (organophosphate) and propoxur (carbamate). Moreover, expression of CYP6AA3, but not CYP6P7, could protect cells against lambda-cyhalothrin cytotoxicity. In MTT assays upon co-incubation with piperonyl butoxide (P450 inhibitor), cytoprotective ability of CYP6P7 and CYP6AA3 against deltamethrin was diminished, implying that pyrethroid detoxification was due to activities of P450 enzymes. Insecticide detoxification capabilities of CYP6P7 and CYP6AA3 observed from MTT assays were correlated to their pyrethroid metabolizing activities observed from in vitro reconstitution enzymatic assays. Thus MTT assays using cells expressing P450 enzymes of interest could be primarily used to determine detoxification activities of enzymes against cytotoxic insecticides. PMID- 22041749 TI - Factors influencing the seasonal abundance of Aedes (Stegomyia) aegypti and the control strategy of dengue and dengue haemorrhagic fever in Thanlyin Township, Yangon City, Myanmar. AB - From June 2006 to May 2007, mosquito surveys were conducted in Thanlyin Township, Yangon City, Myanmar, to determine factors influencing the abundance of Aedes aegypti (Stegomyia aegypti) during the rainy season. Both the biological and environmental factors were included in this study. Increase in the hatchability of egg, larval survival rate, the shortened larval life-span and increased pupation rates supplemented by rainfall (i.e. continuous flooding of the containers, stimulate the continuous hatching of eggs) were observed for correlation with the increase in population density of Ae. aegypti during the rainy season in the study area. Control strategy of Ae. aegypti to analyze the infestation in the community (study area) with larval Ae. aegypti, integrated management measures including health education, attitudes and practices regarding dengue and dengue haemorrhagic fever, transmission of the disease and possible preventive measures, reduction of breeding sites and testing the efficacy of Bacillus thuringiensis israelensis (B.t.i.) with respect to the reduction level of Ae. aegypti larvae in breeding sources, were taken into consideration. PMID- 22041750 TI - Field observation on the efficacy of Toxorhynchites splendens (Wiedemann) as a biocontrol agent against Aedes albopictus (Skuse) larvae in a cemetery. AB - This study explored the efficacy of Toxorhynchites splendens, predator of Aedes albopictus as a biocontrol agent. There was a negative correlation between Ae. albopictus larval population and Tx. splendens larval population in ovitraps (r= 0.287, R2=0.0821). The correlation is higher between the mean number of Ae. albopictus larvae per ovitrap and the number of Tx. splendens larvae in an ovitrap (r=-0.987, R2=0.9737). Larvae of Tx. splendens were observed to co-exist with larvae of Ae. albopictus and Culex fuscocephala in the ovitraps placed in the study area. The existence of Tx. splendens larvae in the study area coincides with their habit, preferring to breed in bamboo stumps. A total of 480 ovitraps were inspected for 30-week study period and 281 ovitraps were positive with Ae. albopictus larvae respectively. There was a significant difference between numbers of ovitrap positive for Ae. albopictus larvae with number of Tx. splendens larvae in the ovitraps (ANOVA, F((4,475)) 2.655, p<0.05). Of 281 ovitraps positive with Ae. albopictus larvae, 255 ovitraps contained only one Tx. splendens larva each. Only one ovitrap contained four, the most number of Tx. splendens larvae (p< 0.05). Thus, Tx. splendens could be utilised as an alternative for dengue vector control programme. PMID- 22041751 TI - Hepatitis B virus (HBV) genotypes in a group of Sri Lankan patients with chronic infection. AB - Hepatitis B infection causes a wide spectrum of liver diseases. Previous analyses of hepatitis B virus (HBV) genome have revealed eight HBV genotypes (A-H), with distinct geographical distribution worldwide. The epidemiology of HBV genotypes and their implications for natural history of disease progression and response to anti viral therapy have been increasingly recognized. This study was undertaken to determine the HBV genotypes in a group of Sri Lankan patients with chronic infection who presented for investigation prior to treatment. Genotypes were determined (2007-2009) in 25 patients with evidence of chronic HBV infection. A genotyping system based on multiplex-nested PCR using type specific primers was employed in assigning genotypes A through F. Genotypes G and H were not determined. Among the 25 patients tested, genotypes B [9 (36%)], C [4 (16%)], D [3 (12%)], A [2 (8%)] and E [1 (4%)] were detected. There was a relatively high prevalence of mixed infections with genotypes B+C (3), A+D (1), and B+D (2), which overall constituted 24% of patients. Although this is a non representative sample, HBV infections among this group of Sri Lankan patients were predominantly genotypes B, C and D. PMID- 22041752 TI - Scanning electron microscopic evaluation of the successful sterilization of Lucilia cuprina (Wiedemann) utilized in maggot debridement therapy (mdt). AB - In Malaysia, maggot debridement therapy (MDT) utilizes maggots of Lucilia cuprina (Wiedemann) to debride necrotic tissue from wound surface, reduce bacterial infection and therefore, enhance wound healing process. To evaluate the sterility of the sterile maggots produced after sterilization process before delivering onto patient wounds. Sterility of sterile maggots is crucial in ensuring the safe usage of MDT and patient's health. Eggs of L. cuprina collected from a laboratory colony were divided into treated group (sterilized) and control group (non-sterilized). Treated group underwent sterilization while eggs from control group were allowed to hatch without sterilization. Sodium hypochlorite and formaldehyde were the main disinfectants used in this sterilization process. Scanning electron microscope (SEM) was used to examine and ascertain the sterility of sterile maggots. SEM results showed that all sterilized L. cuprina eggs and maggots achieved sterility and all were cleared from bacterial contamination. In contrast, all non-sterilized eggs and maggots were found to be colonized by microorganisms. Sterilization method employed to sterilize eggs and maggots used in Malaysia MDT was proven successful and MDT is safe to be used as wound management tools. PMID- 22041753 TI - Mitochondrial DNA and STR analyses for human DNA from maggots crop contents: a forensic entomology case from central-southern China. AB - Insect larvae and adult insects found on human corpses can provide important forensic evidence however it is useful to be able to prove evidence of association. Without this, it could be claimed that the insect evidence was a contaminant or had been planted on the body. This paper describes how mitochondrial DNA (mtDNA) and STR analysis of the crop contents of larvae of the blowfly Aldrichina grahami collected from separated body parts was used to provide evidence of association. PMID- 22041754 TI - Neonatal Plasmodium vivax malaria. AB - Congenital malaria is a condition rarely diagnosed, even in endemic countries. This tropical disease is associated with high mortality in the absence of timely recognition and prompt therapy, particularly when is due to Plasmodium falciparum, however Plasmodium vivax can also lead to relevant morbidity and mortality. We report an unusual case of a 19- day-old male newborn with neonatal vivax malaria, suspected primarily on the basis of positive maternal history, which presented with low birth weight, thrombocytopenia and a significant parasitemia. He responded satisfactorily to chloroquine antimalarial therapy, being successfully discharged 10 days after admission. Blood smears remained negative during the first 2 months of follow up. At 8 weeks of follow up, she showed remarkable weight gain and was developing normally with age appropriate anthropometry with no subsequent complications. PMID- 22041755 TI - Toxicological properties of several medicinal plants from the Himalayas (India) against vectors of malaria, filariasis and dengue. AB - The leaves of five plants namely Nyctanthes arbortistis (Oleaceae), Catharanthus roseus (Apocynaceae), Boenininghusenia albiflora (Rutaceae), Valeriana hardwickii (Valerianaceae) and Eupatorium odoratum (Asteraceae) were selected for the first time from the Garhwal region of north west Himalaya to investigation its toxicological properties against mosquito vectors of malaria, filariasis and dengue. In a laboratory study, using different polarity solvents (petroleum ether, chloroform and methanol) were tested against important larvae of malaria, filariasis and dengue vectors in India. It was observed that petroleum ether fraction of all selected plant possess good larvicidal properties than other solvent fraction. The LC(50) values of isolates from Nyctanthes arbortistis (HAR-1), C. roseus (CAT-1), B. albiflora (BOA-1), V. hardwickii (SUG-1) and E. odoratum (EUP-1) against Anopheles stephensi were 185 ppm, 150 ppm, 105 ppm, 225 ppm and 135 ppm, respectively. The results therefore suggest that the fraction code BOA-1 has excellent larvicidal properties and could be incorporated as botanical insecticides against mosquito vectors with high safety to nontarget organisms. The same fraction was tested against adult vectors of malaria, filariasis and dengue, but no mortality was observed. PMID- 22041756 TI - Screening method for detection of immediate amino acid decarboxylases--producing bacteria implicated in food poisoning. AB - Assessment of amino acid decarboxylase activity can be conducted using tubed broth or plated agar. In this study, the test was carried out in microtitre plates containing lysine, ornithine, arginine, tyrosine, tryptophan, phenylalanine or histidine as biogenic amine precursors. Moller decarboxylase base broth (MDB) with or without 1% of a known amino acid were added to wells of a 96 well-microtitre plate. The wells were inoculated with Escherichia coli, Klebsiella pneumoniae, Acinetobacter anitratus or Staphylococcus aureus to the final concentration of 6.0 x 10(7) cfu/ml and incubated at 35oC. The absorbance of the culture broth was read at 570 nm at 0, 1.0, 2.0, 3.0, 4.0, 5.5, 6.5 and 7.5 hour. Comparison of means of A'(570) between 0 hour and a specified incubation time was determined statistically. Positive decarboxylase activities were detected in the media inoculated with E. coli and K. pneumoniae in less than 6 hours. The current method is suitable for immediate producers of amino acid decarboxylase enzymes. It costs less as it uses less amino acid and it has the potential to be used for screening aliquots of food materials for amino acid decarboxylase activities. PMID- 22041757 TI - Occurrence of gastrointestinal helminths in Bactrian camel in Iran. AB - A study on naturally acquired gastrointestinal helminthic parasites in Bactrian camel was carried out in Ardabil province, northwest of Iran, which is the main site of this species in Iran. This species has importance in Iran due to its low population. A total of 25 faecal samples (25% of population) were examined by Clayton Lane method to determine the egg count of different types of helminths in different age groups. Helminth eggs were found in 13 (52%) of the faecal samples (0-191 eggs/gm, 51.96+/-13.82). Bactrian camels were infected with Nematodirus sp. (32%), Trichuris sp. (32%), Marshallagia sp. (28%), Moniezia sp. (28%) and Strongyloides sp. (16%). The age of the infected Bactrian camels was significantly higher than the non-infected camels (p<0.01) and there was a significant correlation between age and the intensity of infection (r=0.583, p=0.002). No significant difference in the ratio of the affected camels and in the intensity of infection was found between the two sexes. The results of the current study showed that helminthic infection is a serious problem in this animal in Iran. PMID- 22041758 TI - Seasonal distribution of phlebotomine sand flies (Diptera: Psychodidae) in Tham Phra Phothisat temple, Saraburi province, Thailand. AB - Phlebotomine sand flies have long been incriminated as vectors of leishmaniasis in various parts of both the Old and New World. Prompted by recent indigenous cases of leishmaniasis in Thailand, a bionomic study of sand flies was undertaken in Tham Phra Phothisat temple, Saraburi province. In this study, sand flies were collected using Centers for Disease Control (CDC) light traps, to clarify the activity patterns and species composition of the sand flies. Traps were laid from August 2005 to July 2006. The insects were collected monthly between 1800-0600 hours. A total of 8,131 sand flies were collected with a female:male ratio of 1.9:1. Sixteen species were identified, of which 5 belonged to the genus Phlebotomus, 9 to Sergentomyia and 1 to Chinius. Species comprised the abundant species (Sergentomyia silvatica 35.6%, Sergentomyia barraudi 18.1%, Sergentomyia anodontis, 17.1%, Sergentomyia iyengari 11.9%, and Sergentomyia gemmea 11.2%); the less common species (<2%) were Sergentomyia dentata 1.8%, Phlebotomus stantoni 1.1%, Sergentomyia indica 1.0%, Phlebotomus argentipes 0.8%, Sergentomyia perturbans 0.4%, Chinius barbazani 0.3%, Phlebotomus asperulus 0.2%, Phlebotomus philippinensis gouldi 0.1%, Phlebotomus major major 0.1%, Sergentomyia quatei 0.1% and Sergentomyia bailyi 0.1%. The results revealed seasonal variation in sand fly prevalence, with the highest peak in July. Soil samples collected were characterized by alkaline (pH 7.6). PMID- 22041759 TI - Polytene chromosomes of Simulium arakawae, a pest species in the Simulium venustum group (Diptera: Simuliidae) from Japan. AB - The chromosomal relationships of Simulium arakawae, a black fly of medical veterinary importance, are resolved relative to other members of the Simulium venustum species group and to the standard reference map for the subgenus Simulium. Simulium arakawae differs from the subgeneric standard by eight fixed inversions, apparently none of which are shared with any of the other 17 chromosomally studied nominal members of the group. The chromosomal features that indicate group membership might have been lost in S. arakawae, particularly if they were polymorphic in an ancestor. PMID- 22041760 TI - Detection of faecal Cryptosporidium parvum antigen in diarrheic Holstein dairy cows. AB - Over a one-year period, based on a random cluster sampling design, 661 faecal samples from natural cases of diarrheic calves were taken in Fars province of Iran. The samples were taken from the 267 diarrheic calves of high and 394 diarrheic calves of average producing Holstein dairy cows. Faecal samples were collected directly from the rectum. Herd selection was based on geographical location and density of cattle in the region. Samples were collected based on 5 percent of herd population in 4 geographical regions: North, West, East and South of Fars province. The herds were stratified into small, medium and large size. Laboratory investigation consisted of a direct identification test for antigen of Cryptosporidium parvum. All herds had HPDC and APDC Cryptosporidium infected diarrheic calves in their population. Diarrheic Cryptosporidium infected HPDC calves in southern region of Fars province were at much lower risk (P<0.05) than APDC calves. The rate of Cryptosporidium infection in diarrheic APDC calves in southern region of Fars province was highest when compared to other geographical locations. When considering the effect of age, diarrheic Cryptosporidium affected APDC Holstein calves of younger dams (>2 to 3years) showed a higher rate of infection when compared to diarrheic HPDC Cryptosporidium infected ones. There were no differences among the occurrence of Cryptosporidium infection in diarrheic HPDC and APDC calves of different herd size groups. PMID- 22041761 TI - Simulium (Gomphostilbia) sofiani, a new species of black fly (Diptera: Simuliidae) from peninsular Malaysia. AB - Simulium (Gomphostilbia) sofiani sp. nov. is described on the basis of reared adult female, male, pupal and larval specimens collected from Cameron Highlands, Pahang state, Malaysia. This new species is placed in the ceylonicum species group within the subgenus Gomphostilbia and is easily distinguished from all the related known species by the combination of the following characteristics: an elongate sensory vesicle and yellow hair tuft on the stem vein of the wing in the female, the greater number of large upper-eye facets (15 or 16 vertical columns and 15 or 16 horizontal rows) and almost entirely darkened hind basitarsus in the male, and the gill bearing a long common basal stalk and 8 filaments arranged as [(1+2)+(1+2)] +2 filaments from dorsal to ventral in the pupa. PMID- 22041762 TI - How common is intestinal parasitism in HIV-infected patients in Malaysia? AB - Human immunodeficiency virus (HIV)-infected individuals have greater susceptibility to infections by a myriad of microorganisms which can cause significant morbidity and mortality compared to immunocompetent individuals. Of these microbial infections, intestinal parasitic infections (IPIs) however are receiving less attention than bacterial and viral infections, hence, the lack of information of parasitic infections in HIV individuals. Prevalence of IPIs among 346 HIV-infected individuals in Malaysia was determined in this study. The overall prevalence of intestinal parasitic infections (IPIs) was 37.9% (131 of 346) with protozoa infections (18.8%) being more common compared to helminth infections (7.5%). Observed protozoa include Entamoeba histolytica/dispar (16.8%), Cryptosporidium parvum (12.4%), Isospora belli (10.1%), Cyclospora cayetanensis (4.9%) and Giardia duodenalis (intestinalis) (3.2%) whilst helminthes which were detected comprised of Ascaris lumbricoides (13.9%), Trichuris trichiura (6.4%) and hookworms (0.6%). Among those 131 infected, 50.4% had multiple infections and 48.9% had single parasitic infection. The CD4 counts were significantly lower (i.e., 200 cells/mm3) in patients harbouring IPIs. Of those individuals infected with intestinal parasites, 49% were intravenous drug users and 58% were not on any antiretroviral therapy. Most were asymptomatic and had concurrent opportunistic infections (OIs) mainly with Mycobacterium tuberculosis infection. These results confirmed that IPIs are ubiquitous among HIV-infected individuals, especially those presenting with low CD4 T cells counts, and provide useful insights into the epidemiology of these infections among HIV-infected patients in Malaysia. It is therefore recommended, that diagnosis of these intestinal parasitic pathogens should be conducted on a routine basis for better management of gastrointestinal illnesses among HIV individuals. PMID- 22041763 TI - In vitro cultivation of axenic amastigotes and the comparison of antioxidant enzymes at different stages of Leishmania tropica. AB - The present study aimed to establish a simple method to yield large amounts of Leishmania tropica amastigote-like forms in axenic cultures and to compare the superoxide dismutase (SOD) and glutathione peroxidase (GPX) enzymes at different stages of L. tropica. Different culture conditions were tested to find the optimum condition of axenic amastigotes generation. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities were determined at logarithmic and stationary phases and axenic amastigote stage of the parasite. A high proportion (88%) of amastigote-like forms of L. tropica was observed in BHI medium supplemented with 20% FCS, pH 4.5, and incubated at 37oC with 5% CO(2). The results showed that SOD activity was at the lowest level in the logarithmic phase of promastigotes and increased towards the stationary phase of promastigotes and amastigote stage. The results showed that the optimum condition for differentiation of L. tropica promastigotes to axenic amastigotes was BHI medium containing 20% FCS at pH 4.5, incubated at 37oC in the presence of 5% CO(2). It seems that SOD, but not GPX is a major determinant of intracellular survival of the parasite. PMID- 22041764 TI - Treatment outcome of Paederus dermatitis due to rove beetles (Coleoptera: Staphylinidae) on guinea pigs. AB - Linear dermatitis (or dermatitis linearis, DL) is a skin blistering inflammatory lesion caused by exposure to the pederin toxin from rove beetles. Although it is prevalent in many countries of the Middle East region, this is not a notifiable disease. In recent years, a number of clinical symptoms outbreaks of DL has been reported from a few neighboring countries of Iran, but no report of experimental treatment among small laboratory rodents is known. This is a prerequisite to ascertain the nature of the best treatment strategy in cases of infestation with these beetles, as it occurs among local settlers during hot seasons in certain parts of the southern Iranian province of Fars. Live Paederus beetles were collected, identified to species level, sexed apart and partly processed to obtain their hemolymph toxin pederin in ethanol for dermal application on guinea pigs. Two Paederus species were found. Paederus ilsae (Bernhauer) (Coleoptera: Staphylinidae) was more abundant than P. iliensis (Coiffait). Recovery from DL due to live P. ilsae beetles was quicker and less complex than that of pederin in ethanol on guinea pigs. The application of potassium permanganate with calamine to heal DL was also more effective than fluocinolone treatment. This topical corticosteroid is thus considered less able to avert the cytotoxic action of pederin on the skin of guinea pigs than the antipruritic and cleansing agents. It seems likely that fluocinolone has certain effects which delays the recovery period for the treated skin. PMID- 22041765 TI - Insecticide resistance development in Aedes aegypti upon selection pressure with malathion. AB - Bioassay test against malathion had been carried out with larval and adult stages of Aedes aegypti. The mosquitoes were under selection pressure against malathion for forty-five consecutive generations. The rate of resistance development was measured by LC(50) and LT(50) values. The larvae and adult females, after subjection to malathion selection for 45 generations, developed high resistance level to malathion, with resistance ratio of 52.7 and 3.24 folds, respectively over control mosquitoes. Cross-resistance towards the same and different groups of insecticides was determined using the F44 and F45 malathion-selected adult females. Insecticides tested were DDT (4.0%), permethrin (0.75%), propoxur (0.1%), fenitrothion (1%), lambda-cyhalothrin (0.05%) and cyfluthrin (0.15%). Results indicated that the mosquitoes were highly resistant to DDT and fenitrothion, moderately resistant to propoxur, tolerant to permethrin and lambda cyhalothrin, and very low resistant to cyfluthrin. PMID- 22041766 TI - Diversity and killer activity of yeasts in Malaysian fermented food samples. AB - The biodiversity and the killer activity of yeasts isolated from various types of fermented food in Malaysia were investigated in this study. Of 252 yeasts isolated from 48 fermented food samples in this study, 19 yeast species were identified based on sequence analysis of the ITS1-5.8S-ITS2 partial fragments of the yeasts. A total of 29 (11.5%) of the yeast isolates demonstrated killer activity to at least one Candida species tested in this study; including 22 isolates of Trichosporon asahii, 4 isolates of Pichia anomala, and one isolate each of Pichia norvegensis, Pichia fermentans and Issatchenkia orientalis, respectively. The presence of killer yeasts reflects antagonism that occurs during microbial interaction in the fermented food, whereby certain yeasts produce killer toxins and possibly other toxic substances in competition for limited nutrients and space. The anti-Candida activity demonstrated by killer yeasts in this study should be further explored for development of alternative therapy against candidiasis. PMID- 22041767 TI - Cryptococcal osteomyelitis of the femur: a case report and review of literature. AB - Fungal osteomyelitis is a rare opportunistic infection. It exhibits some clinical and radiological similarities to several other bone pathologies. A diagnostic delay may result in significant increase in morbidity. We report a case of a 37 year-old man with underlying hypogammaglobulinaemia presented with isolated cryptococcal osteomyelitis of the femur. PMID- 22041768 TI - Human hydatidosis in Tehran, Iran: a retrospective epidemiological study of surgical cases between 1999 and 2009 at two university medical centers. AB - This study was conducted to evaluate retrospectively 203 patients diagnosed with hydatid cyst disease and treated surgically at two university medical centers between 1999 and 2009 in Tehran, the capital of Iran. Cystic echinococcosis (CE) affected more females 117 (57.6%) than males 86 (42.4%). A remarkable gender difference skewed towards females was observed, and the male/female ratio among CE cases <=20 and >=61 years old was 1.18 and 0.52, respectively. The age of the patients ranged from 8 to 82 years, and the age group 21-40 years (42.8%) was the most affected. A significantly higher number of hydatid cysts were recorded in the liver than in other sites (P<0.001), and more females had higher hepatic cysts (48.8%) than males (35.0%). The ratio of hepatic hydatidosis to pulmonary hydatidosis was about 11. There was a relative direct relationship between the ratio of liver to lung cases and age, and this ratio was significantly (P<0.01) higher in individuals >40 years of age (liver/lung ratio >=43) than in those <40 years of age (liver/lung ratio 2.8-7.6). Unusual cyst locations in kidneys, brain and pelvic area, followed by spleen and spine was also observed. Single organ involvement was found in 95% of the patients, and was more common in females (55.2%) than in males (39.9%). Housewives had the highest rate of infection (53.5%) followed by labourers with 14.8%, which showed a significant difference (P<0.001). Similarly, urban dwellers was also over-represented among the cases (87% urban vs. 13% rural; P<0.001). In 69.5% of cases there was only one cyst, 16.3% had two cysts, 4.7% with three cysts, and 9.5% had four cysts or more. The results showed that further studies are needed to determine the prevalence, economic impact and risk factors of the disease in the area. PMID- 22041769 TI - Sequence analysis on the mitochondrial COXI gene of recent clinical isolates of Plasmodium knowlesi in Klang Valley, peninsular Malaysia. AB - The cytochrome oxidase subunit I (COXI) gene sequences of three recent (2007 2008) clinical Plasmodium knowlesi isolates from Klang Valley, peninsular Malaysia, were determined and compared with those of older (1960's) peninsular Malaysia, recent isolates from Sarawak (on Borneo Island), and an isolate from Thailand. Multiple alignment of the sequences showed that the three clinical isolates were more similar to the older peninsular Malaysia isolates than to those from Sarawak and Thailand. Phylogenetic tree based on the COXI sequences revealed three distinct clusters of P. knowlesi. The first cluster consisted of isolates from peninsular Malaysia, the second consisted of Sarawak isolates and the third composed of the Thailand isolate. The findings of this study highlight the usefulness of mitochondrial COXI gene as a suitable marker for phylogeographic studies of P. knowlesi. PMID- 22041770 TI - Assessing the susceptibility status of Aedes albopictus on Penang Island using two different assays. AB - Routine surveillance on resistant status of field mosquito populations is important to implement suitable strategies in order to prevent pest outbreaks. WHO test kit bioassay is the most frequent bioassay used to investigate the susceptibility status of field-collected mosquitoes, as it is relatively convenient to be carried out in the field. In contrast, the topical application of active ingredient is less popular in investigating the susceptibility status of mosquitoes. In this study, we accessed the susceptibility status of Aedes albopictus Skuse collected from two dengue hotspots on Penang Island: Sungai Dua and Persiaran Mayang Pasir. Two active ingredients: permethrin and deltamethrin, were used. WHO test kit bioassay showed that both wild strains collected were susceptible to the two active ingredients; while topical application assay showed that they were resistant. This indicated that WHO test kit bioassay less sensitive to low level of resistance compared to topical application assay. Hence, topical application is expected to be more indicative when used in a resistance surveillance programme. PMID- 22041771 TI - [Old topic, new perspective: idiopathic pulmonary fibrosis]. PMID- 22041772 TI - [Evaluation of diagnostic methods for sarcoidosis]. PMID- 22041773 TI - [The effect of cyclophosphamide on cytokines in patients with primary Sjogren's syndrome-associated interstitial lung disease]. AB - OBJECTIVE: To investigate the mechanisms of cyclophosphamide sequential therapy for patients with primary Sjogren's syndrome-associated interstitial lung disease (PSS-ILD). METHODS: This was a retrospective review of 15 patients (2005 - 2008) with PSS-ILD who underwent cyclophosphamide sequential therapy. Peripheral blood and bronchoalveolar lavage (BALF) were obtain before and 3, 6, 12, 24 months after the treatment. The TNF-alpha and TGF-beta(1)mRNA levels in peripheral blood were measured using reverse transcription-polymerase chain reaction (RT-PCR). Serum and BALF TNF-alpha, TGF-beta(1)and MMP-9 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) The average levels of serum TNF-alpha (0.39 +/- 0.22) and TGF-beta(1) (0.31 +/- 0.18) mRNA in patients with PSS-ILD were higher compared with that in patients with PSS without ILD. TNF-alpha level (0.23 +/- 0.19) was significantly decreased 3 months after cyclophosphamide treatment (t = 2.533, P < 0.05), and TGF-beta(1) (0.31 +/- 0.18) level markedly decreased after 6 months of treatment (t = 2.617, P < 0.05). (2) The levels of serum TNF-alpha (11.2 +/- 2.6) ug/L, TGF-beta(1) (72 +/- 19) ug/L and MMP-9 (38 +/- 9) ug/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-beta(1) (36 +/- 12) ug/L level decreased significantly after 3 months of treatment (t = 2.526, P < 0.05), and TNF-alpha level (7.1 +/- 1.3) ug/L markedly decreased after 6 months of therapy (t = 2.578, P < 0.05). MMP-9 level (18 +/- 4) ug/L decreased significantly after 12-month treatment (t = 2.329, P < 0.05). (3) The levels of BALF TNF-alpha (17.1 +/- 3.5) ug/L, TGF-beta(1) (36 +/- 17) ug/L and MMP-9 (27 +/- 10) ug/L in patients with PSS-ILD were higher than that in patients with PSS without ILD. TGF-beta(1) (21 +/- 14) ug/L level decreased significantly after 3-month treatment, and TNF-alpha level (9.4 +/- 1.7) ug/L was decreased after 6 months of cyclophosphamide treatment (t = 2.215, P < 0.05). MMP-9 level (13 +/- 5) ug/L decreased after 12 months of cyclophosphamide treatment (t = 2.576, P < 0.05). CONCLUSION: The mechanisms of cyclophosphamide treatment may be associated with its inhibition on production of TNF-alpha, TGF-beta(1)and MMP-9. PMID- 22041774 TI - [The effect of plasminogen activator inhibitor-1 on embryonic lung fibroblasts from rats]. AB - OBJECTIVE: To explore the effect of plasminogen activator inhibitor-1 (PAI-1) on the proliferation and conversion of rat embryonic lung fibroblasts and the synthesis of collagen, and therefore to explore the function of PAI-1 in pulmonary fibrosis. METHODS: The embryonic lung fibroblasts from pregnant Wistar rats were isolated and cultured in vitro. The reproduction rate of fibroblasts at 12 h, 24 h, and 48 h after being stimulated by PAI-1 with different concentrations (5, 10, 20, 40, 80, and 100 ug/L) was measured by MTT assay. After being stimulated by PAI-1 with the most suitable concentration (20 ug/L) for 48 h and 72 h, the expression of proliferating cell nuclear antigen (PCNA) was measured by immunocytochemical technique, and the mRNA expression of alpha-SMA and type-1 collagen at 24 h and 48 h was measured by real-time PCR. RESULTS: PAI 1 with different concentrations stimulated the proliferation of fibroblasts. The highest proliferation rate and absorbance in concentration of 20 ug/L and at 12 h were 62.6% and 0.573 +/- 0.039. The comparison of different concentrations showed that the difference was significant (F = 111.112, P = 0.000). Therefore, 20 ug/L was selected as the most suitable concentration. Using immunocytochemical method, the optical density of PCNA at 48 h and 72 h were 3685 +/- 686 and 2530 +/- 477 after being stimulated with 20 ug/L PAI-1. The comparison showed significant difference (F = 7.85, P = 0.02). The expression of alpha-SMA increased (230 +/- 11)% and (159 +/- 9)% at 24 h and 48 h after being stimulated with 20 ug/L PAI-1, and the difference was significant (F = 39.92, P = 0.0003). The expression of type-1 collagen increased (92 +/- 8)% and (65 +/- 12)%, the difference being significant (F = 32.61, P = 0.0006). CONCLUSION: PAI-1 can promote the proliferation and conversion of fibroblasts and the synthesis of collagen, which may be involved in the pathogenesis of pulmonary interstitial fibrosis. PMID- 22041775 TI - [The values of fractional exhaled nitric oxide in the diagnosis and treatment of chronic cough]. AB - OBJECTIVE: To evaluate the values of fractional exhaled nitric oxide (FENO) in the diagnosis and treatment of chronic cough. METHODS: Based on the protocol from The Chinese Respiratory Society guidelines for management of cough, 75 consecutive subjects with chronic cough and normal chest radiographs were recruited from the outpatient clinic of the Department of Respiratory Diseases in China-Japan Friendship Hospital from January to June 2010. All the patients accepted FENO tests, sputum cell counts, pulmonary function tests, bronchial hyperresponsiveness (BHR), serum IgE, cough symptom scores and Leicester cough Questionnaire (LCQ) before and after treatment of 4 weeks. RESULTS: The final diagnosis of the subjects included 29 with cough variant asthma (CVA), 19 with eosinophilic bronchitis (EB) and 27 with other causes (Others). FENO levels in CVA (58 +/- 26) ppb were significantly higher than those in EB (36 +/- 18) ppb and Others (20 +/- 7) ppb, and the FENO levels in EB were higher than Others (F = 28.2, P < 0.01). FENO levels showed significant correlations with sputum eosinophils, BHR, cough symptom scores, non-specific IgE, and LCQ scores. The mean baseline FENO level of the subjects whose coughs were relieved after inhaled corticosteroid therapy was (63 +/- 42) ppb, higher than those of the non responders (28 +/- 13) ppb (t = 3.91, P < 0.01). There were significant correlations between the percentage of FENO decrease and the percentage of sputum eosinophil decrease or the cough symptom score decrease. CONCLUSION: FENO could be used as a inflammation marker of chronic cough because of its good correlation with sputum eosinophils, AHR, atopy, and cough symptoms. FENO also has a potential to predict the response of anti-inflammatory therapy because FENO decrease is correlated with the decrease of eosinophilic inflammation and improvement of cough symptoms. PMID- 22041776 TI - [A case-control study of the transmission of pandemic influenza A (H1N1) virus in families]. AB - OBJECTIVE: To explore the characteristics of transmission of pandemic influenza A/H1N1, and to analyze the possible factors of influencing transmission in families and to provide scientific evidence for formulating strategies of H1N1 prevention and control. METHODS: A 1:2 matched case-control study was conducted. The case was defined as a household with 2 or more cases and the control was defined as that with 1 case. Face-to-face interview with questionnaire was used to collect information of work and family life of the study participants. Conditional logistic regression was used to analyze the data. RESULTS: Univariate analysis showed that factors such as education level of the secondary case, the number of family members, per capita living space, flu-like symptom, insulation of case, ventilation, hand-washing, and influenza A/H1N1 vaccine immunization were all associated with infection of influenza A/H1N1. Results of multivariate logistic regression analysis showed that variables such as education level of secondary case (OR = 0.42), insulation of case (OR = 3.29), ventilation, (OR = 0.28), hand-washing (OR = 0.71), influenza A/H1N1 vaccine immunization (OR = 0.05) were all correlated to infection of influenza A/H1N1. CONCLUSIONS: Factors such as vaccine, insulation, ventilation, and hand-washing can help persons in protection from infection of influenza A/H1N1, suggesting the importance of good hygienic habit and immunization with influenza A/H1N1 vaccine. PMID- 22041777 TI - [Application of Berlin questionnaire in the screening of obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To investigate the value of Berlin questionnaire in screening obstructive sleep apnea hypopnea syndrome (OSAHS) among Chinese. METHODS: A total of 302 cases with suspected OSAHS were referred to our sleep laboratory. The Berlin questionnaire scores and polysomnography (PSG) monitoring data were analyzed. According to the Berlin questionnaire score, the patients were divided into high and lower risk groups for OSAHS. In terms of the PSG monitoring results, the patients were classified into non-OSAHS, mild, moderate and severe OSAHS groups. The age, gender, apnea hypopnea index (AHI), body mass index, and the Berlin questionnaire (BQ) result were compared among the 4 groups. The correlation of Berlin questionnaire result with age, AHI, the lowest SpO2 (LSpO2) and microarousal index (MAI) were analyzed. RESULTS: There were significant differences in the Berlin questionnaire results among non-OSAHS and the other 3 groups (chi(2) = 13.961, 8.466, 42.156, P < 0.0083); and between the severe OSAHS and the other 2 groups (chi(2) = 9.439, 11.162, P < 0.0083). There was no statistical difference between the mild and moderate groups (P > 0.0083). The ratio of the high BQ risk patients had an increasing tendency as the severity of OSAHS was increased (chi(2) = 34.211, P < 0.01). The Berlin questionnaire results showed a positive correlation with age, AHI or MAI (r = 0.125, 0.346, 0.198, all P < 0.05, respectively) but a negative correlation with LSpO2 (r = -0.371, P < 0.01). The Berlin questionnaire results showed no correlation with gender (P > 0.05). The sensitivity and the specificity of the Berlin questionnaire in predicting sleep apnea were 0.71 and 0.72, respectively. CONCLUSIONS: With the moderate sensitivity and the specificity, the Berlin questionnaire has some value in screening patients with OSAHS. However, it is not correlated with the severity of OSAHS in Chinese patients. Thus Berlin questionnaire has limited value in the screening of OSAHS among Chinese. PMID- 22041778 TI - [Expression of P-glycoprotein and multidrug resistance-associated protein in peripheral blood mononuclear cells from multidrug resistant tuberculosis patients]. AB - OBJECTIVE: To evaluate the expression of P-glycoprotein (P-pg) and multidrug resistance-associated protein (MRP) mRNA levels in peripheral blood mononuclear cells from multidrug resistant tuberculosis (MDR-TB) patients. METHODS: The subjects of this study included 3 groups: a non-TB control group, a TB control group and a MDR-TB group. The 31 subjects in the non-TB control group were staff from Wuhan Tuberculosis Prevention and Treatment Institute. The 55 cases in the TB control group were in-patients during September 2004 to December 2007 who were diagnosed as having pulmonary tuberculosis. The 89 cases in the MDR-TB group were in-patients during the same period, but who were diagnosed as having MDR-TB. Peripheral mononuclear cells were isolated and mRNA levels of P-pg and MRP were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK q was used for comparison between 2 groups. RESULTS: There was no significant difference in the relative P-pg mRNA levels among the MDR-TB group (1.34 +/- 0.32), the non-TB control group (1.05 +/- 0.16) and the TB control group (1.12 +/- 0.23), F = 0.536, P > 0.05. The relative MRP mRNA level (3.45 +/- 0.43) was the highest in the MDR-TB group (3.45 +/- 0.43), as compared to the TB control group (1.23 +/- 0.34) and the non-TB control group (1.04 +/- 0.12), F = 24.241, P < 0.05. CONCLUSION: Higher expression of MRP in peripheral mononuclear cells might be related to multidrug resistance in MDR TB patients. PMID- 22041779 TI - [The effect of erythromycin on transforming growth factor-beta(1) and secretory leukocyte proteinase inhibitor in a rat model of chronic obstructive pulmonary disease]. AB - OBJECTIVE: To study the protective mechanism of erythromycin in the process of COPD. METHODS: Thirty-six male Wistar rats, grade SPF, weight (220 +/- 20) g, were randomly divided into 3 groups, 12 each: a control group, a COPD model group and an erythromycin treated group. Measurement of rat pulmonary function and the pathological changes were performed, and the expression of transforming growth factor-beta(1) (TGF-beta(1)) and secretory leukocyte proteinase inhibitor (SLPI) in the lung of rats were evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Analysis of variance, pairwise comparison between groups using SNK-q test, Pearson linear correlation analysis were carried out for statistical analysis. RESULTS: The rats in the COPD model group showed sign of less activity, loss of appetite and weight, dry and yellow hair, and sometimes wheezing, which were less or milder in the group treated with erythromycin. FEV(0.3)/FVC [(58 +/- 7)%] and Cdyn [(0.16 +/- 0.07) L/cm H2O, 1 cm H2O = 0.098 kPa] were significantly lower in the model group as compared to the control group [(83 +/- 7)% and (0.33 +/- 0.16) L/cm H2O], RI [(0.69 +/- 0.14) cm H2O*L(-1)*s(-1)], but was significantly higher than the control group [(0.33 +/- 0.11) cm H2O*L(-1)*s(-1)]. FEV(0.3)/FVC [(65 +/- 9)%] and Cdyn [(0.23 +/- 0.08) L/cm H2O] were significantly higher in the erythromycin treated group as compared to the model group [(58 +/- 7)% and (0.16 +/- 0.07) L/cm H2O], RI [(0.50 +/- 0.13) cm H2O*L(-1)*s(-1)], but was significantly lower than the model group [(0.69 +/- 0.14) cm H2O*L(-1)*s(-1)]. The expression of TGF-beta(1)protein (integral optical density value) and mRNA (absorbance value) (6.7 +/- 1.5 and 0.45 +/- 0.13) were lower in the erythromycin treated group as compared to the model group (10.7 +/- 1.9 and 0.66 +/- 0.18), but the expression of SLPI protein (integral optical density value) and mRNA (absorbance value) (9.9 +/- 1.7 and 0.69 +/- 0.34) were higher than those of the model group (8.1 +/- 1.7 and 0.41 +/ 0.27). The expressions of TGF-beta(1)and SLPI were negatively associated (r = 0.686, P < 0.05). CONCLUSIONS: The expression of SLPI was decreased but the expression of TGF-beta(1)was increased significantly in the bronchial and lung tissues of rats with COPD. Airway inflammation was inhibited by erythromycin which was able to reduce the inhibitory effect of TGF-beta(1)to SLPI, indicating a partial protective effect of erythromycin. PMID- 22041780 TI - [Recent advances in IgG4-related lung disease]. PMID- 22041781 TI - [Research status of smoking cessation methods for chronic obstructive pulmonary disease]. PMID- 22041782 TI - [Progress of research on angiotensin-converting enzyme 2 in lung diseases]. PMID- 22041783 TI - Supramolecular dioxygen receptors composed of an anionic water-soluble porphinatoiron(II) and cyclodextrin dimers. AB - Three types of per-O-methylated beta-cyclodextrin dimers, Im2CD, Im3NHCD and Py3NHCD, were prepared as globin models. Im2CD was synthesized by the condensation reaction of mono(2(A)-amino)-per-O-methylated beta-cyclodextrin with 3-(1H-imidazol-1-yl)pentanedioic acid. Im3NHCD and Py3NHCD were obtained through the S(N)2 reactions of mono(2(A),3(A)-epoxy)-per-O-methylated beta-cyclodextrin with 3-(1H-imidazol-1-yl)pentane-1,5-diamine and 3,5-bis(aminomethyl)pyridine, respectively. These cyclodextrin dimers formed 1:1 supramolecular inclusion complexes of tetrakis(4-sulfonatophenyl)porphinatoiron(II) (Fe(II)TPPS) in aqueous solution. The supramolecular complexes bound dioxygen (O(2)), with the O(2) affinity of the Fe(II)TPPS/Im3NHCD complex (P(1/2)(O2) = 1.5 +/- 0.1 Torr) being much higher than those of the Fe(II)TPPS/Im2CD (36 +/- 2 Torr) and Fe(II)TPPS/Py3NHCD complexes (70 +/- 5 Torr). On the basis of the results of the present study and previous results, it is concluded that the imidazole axial ligand at the linker attached at the 3- and 3'-positions of the cyclodextrin units causes higher O(2) affinity as compared with the imidazole ligand at the 2- and 2'-positions and the pyridine ligand at the 2,2'- or 3,3'-positions. The electron donating ability and orientation of the axial ligand may control the O(2) affinity of a supramolecular receptor. PMID- 22041784 TI - The relation between 6-n-propylthiouracil sensitivity and caries activity in schoolchildren. AB - Caries activity tests are being used to assess caries risk in children. In recent years the purpose of most studies has been to develop practical, quick, reliable and economic tests. Clinical studies showed that the difference in sensitivity to the bitter taste of 6-n-propylthiouracil (PROP) is a heritable trait and may influence children's nutritional habits and caries development. The aim of this study was to investigate the relation between PROP sensitivity and caries activity in schoolchildren, in comparison with different caries activity tests. One hundred and twenty children aged between 7 and 12 years (mean age 9.97 +/- 1.59) were investigated to determine socioeconomic status and oral hygiene habits, fluoride consumption, DMFT, DMFS, df, dfs, plaque indexes, and nutritional habits. Children were divided into three groups according to their caries risk status based on the Cariogram. The solution test and the PROP impregnated filter paper test were used together to determine PROP sensitivity. After all associated factors had been controlled, stepwise regression analyses revealed that DMFT and dfs scores were important determinants of PROP. According to dfs, the sensitivity of the Cariogram and of PROP tests was 0.85 and 0.70, respectively, and specificity was 0.32 and 0.33, respectively. There was an inverse significant relationship between PROP sensitivity and DMFT, DMFS, and dfs results (p < 0.01). In conclusion, PROP nontasters were significantly more likely to have high caries risk than PROP tasters (p < 0.01). PMID- 22041788 TI - LC-MS-based metabolomics. AB - Metabolomics aims at identification and quantitation of small molecules involved in metabolic reactions. LC-MS has enjoyed a growing popularity as the platform for metabolomic studies due to its high throughput, soft ionization, and good coverage of metabolites. The success of a LC-MS-based metabolomic study often depends on multiple experimental, analytical, and computational steps. This review presents a workflow of a typical LC-MS-based metabolomic analysis for identification and quantitation of metabolites indicative of biological/environmental perturbations. Challenges and current solutions in each step of the workflow are reviewed. The review intends to help investigators understand the challenges in metabolomic studies and to determine appropriate experimental, analytical, and computational methods to address these challenges. PMID- 22041790 TI - Oligohydramnios, small for gestational age and pregnancy outcomes: an analysis using precise measures. AB - BACKGROUND/AIM: Marginal or decreased amniotic fluid volume by ultrasound estimate and fetal growth restriction have been shown to be significantly associated with perinatal mortality. The association of fetal growth restriction and precisely measured amniotic fluid volume is unknown. The purpose of this study was to determine if adverse pregnancy outcomes are more likely in pregnancies complicated by small-for-gestational-age (SGA) neonates and dye determined oligohydramnios. METHODS: Admissions to neonatal intensive care unit (NICU) and other pregnancy outcomes were analyzed in parturients with known amniotic fluid volume, calculated by the dye-dilution technique. The pregnancy outcomes of those with oligohydramnios and SGA were compared with pregnancies complicated by just one of these two conditions and pregnancies with normal fluid and birth weight. RESULTS: Of 202 patients, oligohydramnios was present in 26% (53), SGA in 15% (30) and both conditions in (5%) (11). Logistic regression, controlling for gestational age, demonstrated that the combination of oligohydramnios and SGA, compared to normal growth and fluid strongly predicted NICU admission (OR 11.1; 95% CI 2.1-59.2) but not other complications. (OR 4.8; 95% CI 0.3-62.9). CONCLUSIONS: SGA with oligohydramnios significantly increases the likelihood of a NICU admission, but not other morbidity. PMID- 22041791 TI - Content and completeness of care plans after implementation of standardized nursing terminologies and computerized records. AB - The nursing process and standardized nursing terminologies are essential elements to structure nursing documentation in daily nursing information management. The aim of this study was to describe sustainability and whether and how standardized nursing terminologies, in handwritten versus preprinted versus computerized nursing care plans, changed the content and completeness of documented nursing care. Three audits of patient records were performed: a pretest (n = 291) before a yearlong implementation of standardized nursing terminologies in nursing care plans followed by two posttests: (1) 3 weeks after implementation of nursing terminologies (n = 299) and (2) 22 months after implementation of nursing terminologies and 8 months after implementation of a computerized system (n = 281) in a university hospital. Content and completeness of documented nursing care improved after implementation of standardized nursing terminologies. Documentation of nursing care plans, signs and symptoms, related factors, and nursing interventions increased, whereas mean number of nursing diagnoses per patient did not change between audits. Computerized nursing care plans had the biggest impact, with more variety of nursing diagnoses and increased documentation of signs and symptoms, related factors, and nursing interventions. The use of standardized nursing terminologies improved nursing content in the nursing care plans. Moreover, computerized nursing care plans, in comparison with handwritten and preprinted care plans, increased documentation completeness. PMID- 22041789 TI - The rice thylakoid lumenal cyclophilin OsCYP20-2 confers enhanced environmental stress tolerance in tobacco and Arabidopsis. AB - The role that the putative thylakoid lumenal cyclophilin (CYP) CYP20-2 locates in the thylakoid, and whether CYP20-2 is an essential gene, have not yet been elucidated. Here, we show that CYP20-2 is well conserved in several photosynthetic plants and that the transcript level of the rice OsCYP20-2 gene is highly regulated under abiotic stress. We found that ectopic expression of rice OsCYP20-2 in both tobacco and Arabidopsis confers enhanced tolerance to osmotic stress and extremely high light. Based on these results, we suggest that although the exact biochemical function of OsCYP20-2 in the thylakoid lumen (TL) remains unclear, it may be involved in photosynthetic acclimation to help plants cope with environmental stress; the OsCYP20-2 gene may be a candidate for enhancing multiple abiotic stress tolerance. PMID- 22041792 TI - Highly diastereoselective Friedel-Crafts reaction of arenes with N-tert butanesulfinylimino ester towards the efficient synthesis of alpha-arylglycines. AB - Lewis acid-catalyzed highly diastereoselective asymmetric Friedel-Crafts alkylation of arenes with a chiral N-tert-butanesulfinylimino ester is described. The reaction can be accomplished with ease in the presence of a catalytic amount of In(OTf)(3) at room temperature, providing a series of enantiomerically enriched alpha-arylglycines in good yields and with excellent diastereoselectivities (up to 99% de). Highly stereoselective double Friedel Crafts alkylation to afford dialkylation product was also investigated. PMID- 22041793 TI - Laboratory evaluation in patients with anorexia nervosa: usefulness and limits. AB - OBJECTIVE: Eating Disorders (ED), anorexia nervosa (AN) in particular, are significant causes of morbidity and mortality. The purpose of this study is to evaluate how laboratory studies can help to diagnose AN and to choose the type of care according to the degree of medical compromission, particularly in primary care. PATIENTS AND METHODS: During the years 2002-2009, in our Eating Disorder Centre, we evaluated 298 ED patients diagnosed by criteria Diagnostic and Statistical Manual of Mental Disorders (DMS-IVR) using anthropometric and laboratory tests. RESULTS: In our 298 ED patients we identified 264 with a BMI value below 17.5 Kg/m(2) (Anorexia Nervosa patients) and 34 subjects with a BMI higher than 17.5 Kg/m(2), but lower than 20 (Eating Disorder Not Otherwise Specified patients). Sixty percent of the subjects showed normal values with respect to the 38 common laboratory tests used in the clinical setting. In the subgroup of AN patients with more severe malnutrition (BMI lower than 14.15 Kg/m(2)), the percentage of abnormal laboratory values was higher, but always below fifty percent; in 19 laboratory test we found a significant correlation between the BMI value and that of the laboratory test. CONCLUSIONS: The laboratory tests may result as normal even in AN subjects with severe malnutrition and their use without a multi-dimensional evaluation may be misleading, and can even delay the care of patients. PMID- 22041794 TI - Knowledge of iodoprophylaxis and iodized salt consumption among medical students in Italy. AB - OBJECTIVES: Iodine deficiency is still a notable health-care problem in several regions of Europe and can be responsible for maternal and fetal goiter, miscarriages, stillbirths, reduced fetal growth, congenital hypothyroidisms, damaged reproduction in adult life, and inadequate development and maturation of the fetal brain, which is the major preventable cause of mental defects. The aim of this study was to assess the medical students' knowledge and practices regarding the program of iodized-salt-use and active iodine prophylaxis program launched by the Italian Ministry of Health. MATERIALS AND METHODS: A self administered, anonymous, 19 single-item questionnaire was developed. We have collected 294 filled forms: 86 from first-year, 118 from fourth-year and 90 from sixth-year medical students at the First Medical School of 'Sapienza' University of Rome, Italy, in May 2009. RESULTS: Two hundred eighty four students (96.6%) affirm that they know of the existence iodized salt, even though only 199 (67.7%) report personal consumption. This level is quite far from the target (consumption by almost 80% of the general population) suggested by the international literature. No statistically relevant difference was observed between the answers of male and female students. CONCLUSIONS: Our study proves that clinical students have a more detailed knowledge on iodized salt if compared with pre-clinical students, but such knowledge remains overall defective and in some cases absolutely incorrect. Additional education is probably needed to prepare physicians to play a critical role in counseling about iodine prophylaxis. PMID- 22041795 TI - [Pain assessment in terminally-ill cancer patients on admission in hospice and its modification after the first three days of care. A monocentric experience]. AB - AIMS: Pain is among the most frequent and distressing symptoms in terminally-ill cancer and, to date, many patients still experience uncontrolled pain. In this paper we evaluated prevalence and intensity of pain on admission in our palliative care center and during the first three days of care. PATIENTS AND METHODS: From September 2009 to October 2009 we consecutively recruited 96 terminally-ill cancer patients : on admission more than 50% had severe pain and only 4% referred to be pain-free. 54% of patients was on treatment with strong opioids. RESULTS: After three days from admission in our palliative care unit only 7% of patients experienced severe pain, 25% reported absence of pain and 80% of patients was on treatment with strong opioids. CONCLUSIONS: The beginning of palliative care led to a meaningful and rapid reduction of pain in the vast majority of terminally-ill cancer patients evaluated in this study. PMID- 22041796 TI - Foramina on the zygomatic bone: its clinical significance. AB - AIM: To study the anatomy of zygomatico-orbital, zygomatico-facial and zygomatico temporal foramina in south Indian population. MATERIALS AND METHODS: 50 dry adult skulls of south Indian origin were studied. The number of ZO, ZF and ZT were recorded on each side. The distances of these foramina to the nearest palpable bony points, infero-lateral angle of the orbit and infra-orbital foramen were measured using Vernier's calipers. RESULTS: Variable number of ZO and ZF foramina, ranging from 0 to 4 was seen. Single ZO foramen in 56% and 44%, double in 6% and 12%, absent in 38% and 44% on right and left sides were seen. Distance of ZO foramen from inferolateral angle of orbit was 9+2.51 mm and 7.8+1.74 mm on right and left side respectively. The mean distance from infraorbital foramen was 29.93+2.76 mm and 30.19+ 3.52 mm on right and left side respectively. Single ZF foramen in 40% and 42%, double in 10% and 8%, 3 in 4% on right side and 4 in 2% on left sides were seen. In the remaining 46% and 48% of bones, the ZF foramen was absent. Mean distance from inferolateral angle of orbit was 8.05+2.68 and 9.15+2.11 mm respectively on the right and left side. Mean distance from infraorbital foramen was 25.45+4.35 mm and 25.42+4 mm respectively on right and left side. CONCLUSION: The location of ZO and ZF foramen can be population specific and knowledge of its location is important during stabilization of zygomatic fractures, in endoscopic subperiosteal facelift. PMID- 22041797 TI - Unilateral anomalous brachial and antebrachial musculature associated with duplication of anterior interosseous nerve: a case report. AB - The present case aims to provide an accurate anatomical description of coexistent accessory heads of flexor pollicis longus in the arm and forearm, extra muscular slips of the accessory belly of flexor pollicis longus to flexor digitorum profundus, and double anterior interosseous nerves. The morphology of the anomalous accessory muscle bellies is correlated with their clinical significance and embryological basis. Knowledge of such muscular and neuroanatomical variants is imperative prior to traumatic evaluation and reconstructive surgery. PMID- 22041798 TI - Aortic aneurysm: a case report with emphasize on microscopic and surgical anatomy. AB - We report a case of fusiform type of abdominal aortic aneurysm which was found during the routine dissection of a cadaver, done for teaching the undergraduate medical students. The aneurysm was seen unruptured and positioned below the renal arteries, just above the aortic bifurcation. This study illustrates the microscopic and surgical anatomy of the aneurysm with added literature review and clinical implications. We believe that the knowledge of this vascular pathology will be enlightening for broad specialties of medicine and medical science researchers alike. PMID- 22041799 TI - Papillary thyroid cancer in a young woman affected by giant congenital melanocytic nevus, ultrasound diagnosis. AB - Data literatures report numerous association between giant congenital nevus and development alteration; only two cases describe its coexistence with thyroid disorders. However, we report the association of papillary thyroid cancer and giant congenital nevus. Papillary thyroid cancer is the most common differentiated thyroid cancer and has high prevalence in young women. In this paper we report: the case of a 18 years-old woman, affected by giant congenital melanocytic nevus on her back, who came to our observation because of one month of fever and increased volume of latero-cervical lymph nodes. Negative serologic tests allowed us to exclude lymphoma and mononucleosis. Because of the high risk (6%) that giant congenital melanocytic nevi could transform into malignant melanoma, we performed an ultrasound examination (US) of the cervical lymph nodes. The examination extended to the thyroid gland enabled us to visualize the same parenchyma alteration in both thyroid gland and lymph nodes. At last, fine needle percoutaneus aspiration on thyroid lesion confirmed the presence of papillary carcinoma. In our case, thank to the optimal visualization of the parenchyma structure, US was diriment allowing a diagnosis of primitive thyroid lesion with an involvement of all lymph nodes in the neck. This findings legitimate the role of US as an accurate, noninvasive, radiation free and low cost imaging technique in detecting differential diagnosis in the cervical lymphadenopathy, as well in preoperative staging thyroid carcinoma. PMID- 22041800 TI - Anomalous disposition of profunda femoris artery: a clinicoanatomical appraisal. AB - During educational dissection of the left lower limb of an adult Indian male cadaver, an unusual variation of the branches of the femoral artery and profunda femoris artery (PFA), were observed. The profunda femoris artery and medial circumflex femoral artery took origin from a common arterial trunk from the medial side of femoral artery. The PFA coursed lateral to the femoral vein. The lateral circumflex femoral artery (LCFA) took origin, 1.2 cm proximal to the origin of the latter. The lateral circumflex femoral artery (LCFA) took origin directly from the femoral artery. The femoral vein was constantly medial to the PFA and coursed between it and femoral artery. The great saphenous vein was observed to course medial to the PFA and at its termination coursed anterior to the latter to drain into the femoral vein. Changes in caliber of femoral artery were recorded at the site of origin of the variant branches. PMID- 22041801 TI - An unique case of dyspareunia leading to the diagnosis of urachal cyst in a nulliparous 28-year-old woman. AB - Urachal cysts are usually asymptomatic. Symptoms, when present, are usually acute abdominal pain, fever, midline hypogastric tenderness, palpable mass, evidence of urinary infection or haematuria due to infection of the cyst. We report an unique case of dyspareunia and "abdominal fluid flowing feeling" caused by an urachal cyst in a 28 year-old nulliparous woman. Diagnosis was achieved by US and MRI. Cystography excluded any cyst-bladder communication. Laparoscopic surgery was performed without perioperative complications. Patient obtained immediate relief of symptoms still continuing at a 24 months follow up. PMID- 22041802 TI - Efficacy of electrochemotherapy in ulcerated basal cell carcinoma. AB - Basal cell carcinoma is the most common cutaneous malignant tumor, accounting for up to 80% of non melanoma skin cancers. Surgery, radiotherapy and chemotherapy have been for long time the main options for its treatment. Electrochemotherapy (ECT) is a novel local treatment successfully used in primary skin tumors. We report a case of a man affected by ulcerated basal cell carcinoma treated with ECT. In our case ECT was successful in the management of extensive basal cell carcinoma in clinical conditions whereas other approaches, would have been dangerous and inappropriate. To our knowledge, ECT must be considered as an alternative of traditional techniques when they are contraindicated in relation to the appearance of the lesions or the patient medical history. PMID- 22041803 TI - Atypical (symplastic) leiomyoma of the uterus--a case report. AB - A 30-year-old, nulliparous woman presented with a history of subfertility. On examination she was found to have uterine fibroid of 28 weeks size of gravid uterus and subsequently laporatomy myomectomy was performed. Multilobulated masses, with diameters ranging from 22 mm to 160 mm were found. Cut sections of the lobulated masses showed whitish whorled cut surface. One of the multilobulated masses had a cystic cavity, measuring 60x50x35 mm(3). Light microscopic findings of the mass with the cystic cavity showed a well circumscribed cellular tumour composed of cells exhibiting moderate nuclear atypia which were enlarged, nuclei with prominent chromatin clumping and were distributed in areas. Some tumour cells showed large nuclear pseudoinclusions, multinucleated or multilobated tumour giant cells, smudging and few enlarged nucleoli. Mitotic activity was 4 MFs per 10 HPFs. Occasional cells with intracytoplasmic inclusions resembling rhabdoid - like features were seen. There were no atypical mitoses or tumour necroses were noted. Diagnosis of atypical leiomyoma or symplastic leiomyoma was made. Atypical or symplastic leiomyomas are rare in the region of Malaysia and the present case discusses its incidence in younger age, its morphological features along with diagnosis and clinical outcome. PMID- 22041804 TI - Gallbladder metastases of breast cancer: from clinical-pathological patterns to diagnostic and therapeutic strategy. AB - Gallbladder metastasis of breast cancer are rare, particularly linked to lobular histotype and synchronous just in 1/4 cases. A review of the literature has been performed aimed to evidence the patterns of gallbladder metastases of breast cancer finding 15 cases to whom we added a 48 years old post-menopausal woman. 3 weeks after surgery for mixed ductal-lobular breast carcinoma she showed at the abdominal ultrasound, performed for staging, diffuse thickening of the gallbladder wall , coherent with a chronic cholecystitis and with the mild right upper-abdominal pain that the patient complained in the last months. After laparoscopic cholecystectomy, the pathology report showed a metastatic lobular carcinoma of the breast. Two years later she presented with SNC metastases and died four months later. Lobular histotype is the most frequent breast neoplasm associated with gallbladder metastases. Usually metachronous, these metastases are sinchronous in 28% of cases. Symptoms are usually linked to coexisting acute or cronic cholecystitis. Rarely massive invasions lead to acute abdomen or jaundice. Imaging is rarely diagnostic for neoplasm. Our experience and data from literature lead to careful evaluate every anomaly observed in breast cancer patients. A careful evaluation of abdominal symptoms and of routine imaging examinations performed for staging and for treatment planning, could consent to detect and radically treat the metastases and appropriately assign the chemotherapy. Such approach can lead to discrete survival even in these unfortunate patients. Surgeons and gastroenterologists should be aware of the risk hidden behind apparently benign, mild diseases in such patients. PMID- 22041805 TI - [Extramotor disorders in amyotrophic lateral sclerosis: multisystem disease?]. AB - The purpose of this article is to review several studies on extramotor feature in Amyotrophic Lateral Sclerosis (ALS), its association with cognitive impairment, dementia, sensory and autonomic abnormalities suggesting that ALS is a multisystem disorder rather than a pure motor neuron disease. Evidence from neuroimaging, neuropsychological and histologic studies suggests that other brain regions can be involved in the pathologic process. However, the extent of the extramotor involvement remains unclear. A recent finding on the deposition of pathological TDP-43 (43 kDA transactivating responsive sequence DNA binding protein) in the Central Nervous System of Amyotrophic Lateral Sclerosis patients implies that ALS may be situated of clinicopathological spectrum of multisystem degeneration including Fronto-Temporal Lobar degeneration, that is related to the same protein. PMID- 22041806 TI - [Media Studies: a diachronic and cross-curricular approach]. AB - Studies on Media have generated analysis and remarks involving many different disciplines. We have just entered the age of Mass Communication. Each media (papers, radio, movie, TV and web too) wants to interpret reality and offer it to its audience. Each message coming from media is sifted and proposed according to the structural and technical characteristics of the media itself (as M.McLuhan said "the medium is the message"). In time there have been interpretations in favour or against as well, as experts detractors or defenders of media; U Eco called them "apocalyptic" and "integrated". In Medicine there are many different pathologies referable to excessive or incorrect utilization of mass-media: obesity due to high-calorie intake caused by sedentary use of TV, anorexia caused by forced imitation of models created by media, anxiety and sleeping disorders in teen-agers caused by watching TV news. Research are being carried out on mental effort due to incorrect use of screen, similar to the research on VDU operators. Categories gathered from Cognitive Ergonomics are suggested to hypothesize models of correct use of media and maybe the capacity of getting free from the influence of media so that aware audience can have a conscious perspective and not the perception of reality based entirely on the use of any media. PMID- 22041807 TI - [Er:YAG laser: tissue interaction and histomorphological characterization]. AB - Authors describe Er:YAG laser interaction with tissues, in particular their histomorphological characteristics to identify a specific clinic area for laser application through the examination of different clinical international trials. This study includes experimental trials about pig and rat skin laser application to know laser Er: YAG capability and limits; investigation is extended to laser application in human soft tissues as mucosa, periosteum and bones, its utility in cutaneous pathologies and in antiageing treatments. PMID- 22041808 TI - Preliminary evidence of focal muscle vibration effects on spasticity due to cerebral palsy in a small sample of Italian children. AB - AIMS: Effects of muscle mechanical vibration on movement disorders still need accumulation of a pertinent body of evidence. The aim of this study was to explore the effects of repeated muscle vibration stimulation (rMV) using a protocol, previously demonstrated able to induce plastic reorganization of the primary motor cortex in an experimental model. PATIENTS AND METHODS: The study was carried out in a cohort of 8 pediatric patients (6-15 years) with lower limb spasticity due to cerebral palsy. rMV was applied for 3 consecutive days, 30 min/day, with fixed frequency (100 Hz) and low amplitude (<0.5 mm peak-to-peak), on the triceps surae. Outcome was measured using the modified Ashworth scale (MAS) and ankle range of movement (ROM) and spasticity was evaluated at T0, T1 (24 hours afterwards), T2 (30 days afterwards) and T3 (12 weeks afterwards). RESULTS: Spasticity ameliorated with a 40% reduction of the MAS value and a 7.7% improvement of the ankle ROM at T1. Similar results were observed in T2 and T3, thus suggesting long-lasting effects of the treatment. CONCLUSIONS: This study remarks the possible role of rMV in a mini-invasive and cost-effective setting of treatment for spasticity due to cerebral palsy. Further studies are needed in order to confirm this preliminary results. PMID- 22041809 TI - Histological examination of bone fragments of unknown origin. AB - OBJECTIVES: Recognition and identification of bone fragments are of primary importance to confirm or exclude the human origin of skeletal remains. When badly degraded fragments of bone are found, this may be impossible by gross morphology alone, and histological methods have to be used. Aim of this study is to correlate the compact bone tissue microstructure in various classes of mammals, including humans, and birds in order to find an adequate identification key. MATERIALS AND METHODS: We used long bone diaphysis samples. Bone fragments had been fixed in 4% formalin and then decalcified in EDTA (ethylene-diamin-tetra acetate). After decalcification, samples had been processed for routine paraffin inclusion. Transverse sections had been cut and stained with hematoxylin-eosin staining, and examined by light microscopy (Nikon Eclipse E400(r)). RESULTS: The results of our study show that in bone tissue samples from various classes of mammals, including humans, and birds the osteonic structure shows peculiar features, often depending on the rate of bone remodeling, different in different animal species. CONCLUSIONS: We conclude that a careful microscopic analysis of bone tissue and the characterization of distinctive osteonic features could give a major contribution to forensic medicine to obtain a more reliable recognition of bone fragments of unknown origin. PMID- 22041810 TI - Aminaphtone in the treatment of pseudophakic cystoid macular edema: a case report. AB - PURPOSE: Cystoid macular edema (CME) following cataract surgery has been recognized for over 50 years as an important cause of suboptimal post-operative vision. The incidence of CME varies widely, but is likely in the range of 1-2% using modern cataract extraction techniques. We report the case of resolution of post-operative CME after treatment with aminaphtone 75 mg three time a day for one month. METHODS: A 74-year-old causasian woman presented with reduced vision in the left eye after one month from uneventful cataract phacoemulsification. She underwent a complete ophthalmological examination comprehensive of spectral domain optical coherence tomography (SD-OCT) which showed CME and a central foveal thickness (CFT) of 703 micron. The patient was treated with aminaphtone for one month. RESULTS: CME disappeared, the CFT was within normal limits when aminaphtone was ceased, and best corrected visual acuity was 20/20 at the end of the treatment. CONCLUSION: Aminaphtone is a novel proposal in the treatment of pseudophakic cystoid macular edema. PMID- 22041811 TI - Migrating radicular pain caused by gas-collection in the lumbar epidural region: case report. AB - Finding gas into the intervertebral disc space is a relatively common occurrence, whereas lumbar disc herniations containing gas or lumbar epidural gas-collections are rarely observed. The Author reports a very rare case of a patient who first suffered from right-side sciatica and then, a few months after being treated, from left-side cruralgy; both symptoms were found to be caused by epidural gas collection at different levels of the spinal canal. PMID- 22041812 TI - Is non-directive communication in genetic counseling possible? AB - In 2007, over 560,000 genetic tests were performed in Italy. However, only 70,154 genetic counseling sessions were conducted. Some say that non-directive counseling is necessary so that the patient understands the test results and the different options available and that the physician should not influence the patient's free choice. We need to clarify the meaning of non-directive consultation and if it is in fact possible. Each doctor has his own values and, in order to achieve the intended purpose, he will give information that, with his verbal, para-verbal and body language will guide the patient to one decision or another. Taking into account the axiom of effective communication "You can't NOT communicate", non-directive counseling is very difficult or even impossible. In genetic counseling, the knowledge that the patient receives of the correct diagnosis and related medical facts and of the applicable genetic considerations is basic to the entire process. Nonetheless, such knowledge in itself is not sufficient if it cannot be appropriately imparted to the interested person or persons. We think "persuasion" is not the right method, but instead "convince" meaning "co-win", "win together" may be the best approach to a problem of such great importance. The counselor will have achieved the desired goal with his patient if he is able to channel the emotion towards a mutually beneficial objective. The primary goal is not to persuade but to win-together (convince) with the patient and the unborn child. PMID- 22041813 TI - [The ketogenic diet: an underappreciated therapeutic option?]. AB - Obesity is reaching epidemic proportions in Western countries and is a strong risk factor for cardiovascular disease. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Although there is a common agreement about the concept that exercise and diet are two key factors for the control of body weight, the ideal amount and type of exercise and also the ideal diet for weight control are still under debate. A widely accepted nutritional regime is the Mediterranean diet that has evident health benefits although less attention has been paid to see if the effects are due to other lifestyle factors which may contribute to the health benefits perhaps as much as specific food choices. There are several other options available to the physician that may produce good weight loss results in the short/medium term and also for maintenance of the goal achieved. One of these strategies is the ketogenic diet or VLCKD (very low carbohydrate ketogenic diet) that has been widely studied in recent years. Most studies show that this diet has a solid physiological and biochemical basis which is able to induce effective weight loss and improvement of several parameters of cardiovascular risk. This review discusses the physiological basis of VLCKD and the main applications together with its strengths and weaknesses compared to common dietary recommendations. PMID- 22041814 TI - Missing heritability in the tails of quantitative traits? A simulation study on the impact of slightly altered true genetic models. AB - OBJECTIVE: Genome-wide association studies have identified robust associations between single nucleotide polymorphisms and complex traits. As the proportion of phenotypic variance explained is still limited for most of the traits, larger and larger meta-analyses are being conducted to detect additional associations. Here we investigate the impact of the study design and the underlying assumption about the true genetic effect in a bimodal mixture situation on the power to detect associations. METHODS: We performed simulations of quantitative phenotypes analysed by standard linear regression and dichotomized case-control data sets from the extremes of the quantitative trait analysed by standard logistic regression. RESULTS: Using linear regression, markers with an effect in the extremes of the traits were almost undetectable, whereas analysing extremes by case-control design had superior power even for much smaller sample sizes. Two real data examples are provided to support our theoretical findings and to explore our mixture and parameter assumption. CONCLUSIONS: Our findings support the idea to re-analyse the available meta-analysis data sets to detect new loci in the extremes. Moreover, our investigation offers an explanation for discrepant findings when analysing quantitative traits in the general population and in the extremes. PMID- 22041815 TI - Protein-directed reduction of graphene oxide and intracellular imaging. AB - We demonstrate a facile, one-step, protein-directed approach to preparing a new functional reduced graphene oxide via simultaneous reduction and surface functionalization of graphene oxide sheets with herceptin and show its potential application as a novel biological imaging agent. PMID- 22041816 TI - Diagnostic value of some less frequently considered blink reflex parameters in idiopathic trigeminal neuralgia. AB - AIM OF THE STUDY: We have done a study investigating the value of some less frequently considered Blink reflex parameters for establishing the diagnosis of idiopathic trigeminal neuralgia. PATIENTS: The study was done on 50 patients suffering from idiopathic trigeminal neuralgia, diagnosed according to the guidelines of the International Classification of Headache Disorders, with no other apparent illness. METHODS: We have stimulated the supraorbital nerve at the forehead (foramen n. supraorbitalis) and recorded the reflex response on both mm. orbiculares oculi. Incidence of following findings was determined: (1) occurrence of ipsilateral R3 component, (2) prolonged duration (>25 ms) of R2 when stimulating the affected side and (3) occurrence of R1 component during the stimulation of contralateral supraorbital nerve. We have compared these findings to those of 50 healthy subjects from the control group (Chi-square, p < 0.05). Sensitivity, specificity and diagnostic value for individual parameters were determined. RESULTS AND CONCLUSION: All three parameters tested proved to have a significantly higher incidence in the group of subjects. The occurrence of R3 component on the affected side showed the highest diagnostic value. SIGNIFICANCE: We believe these findings could electrophysiologically reinforce the clinically established diagnosis of idiopathic trigeminal neuralgia. PMID- 22041817 TI - Notch signaling mediates p63-induced quiescence: a new facet of p63/Notch crosstalk. PMID- 22041818 TI - Effects of YC-1 on hypoxia-inducible factor 1 alpha in hypoxic human bladder transitional carcinoma cell line T24 cells. AB - OBJECTIVES: It was the aim of this study to explore the effects of 3-(5' hydroxymethyl-2'-furyl)-l-benzyl indazole (YC-1) on transcription activity, cell proliferation and apoptosis of hypoxic human bladder transitional carcinoma cells (BTCC), mediated by hypoxia-inducible factor 1alpha (HIF-1alpha). METHODS: BTCC cell line T24 cells were incubated under normoxic or hypoxic conditions, adding different doses of YC-1. The protein expression of HIF-1alpha and HIF-1alpha mediated genes was detected by Western blotting. RT-PCR was used to detect HIF 1alpha mRNA expression. Cell proliferation, apoptosis and migration activity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and transwell migration assay. The cells were pretreated by two ERK/p38 MAPK pathway-specific inhibitors, PD98059 or SB203580, and then incubated with YC-1 treatment under hypoxic condition. HIF-1alpha protein expression was detected by Western blotting. RESULTS: Hypoxic T24 cells expressed a higher level of HIF-1alpha, vascular endothelial growth factor, matrix metalloproteinases-2, B cell lymphoma/leukemia-2 protein and HIF-1alpha mRNA compared with normoxic controls, in which the above-mentioned expression was downregulated by YC-1 in a dose-dependent manner. Cell proliferation and migration activity were inhibited while apoptosis was induced by YC-1 under hypoxic condition. Moreover, YC-1 downregulated HIF-1alpha expression was reversed by PD98059 and SB203580, respectively. CONCLUSIONS: YC-1 inhibits HIF-1alpha and HIF-1alpha-mediated gene expression, cell proliferation and migration activity and induces apoptosis in hypoxic BTCC. The ERK/p38 MAPK pathway may be involved in YC-1-mediated inhibition of HIF-1alpha. PMID- 22041819 TI - [Lead poisoning and basal ganglia hyperintensities]. PMID- 22041820 TI - [Seizures in neurofibromatosis. What is the risk?]. AB - INTRODUCTION: The prevalence and the type of seizures associated with neurofibromatosis 1 (NF1) and 2 (NF2) are not adequately characterized. STATE OF THE ART: NF1 has a birth incidence of one in 2500, and NF2 one in 25000. Seizures are an occasional complication in NF1 patients and there is no data for NF2 patients. Central nervous system tumors are always suspected, since NF1 and NF2 are caused by mutations in tumor suppressor gene controlling cell proliferation and differentiation. PERSPECTIVES: The aim of this article is to provide a synthetic overview about epilepsy associated with NF1 and NF2 based on published studies. In NF1, the type of seizures and their response to therapy are reported, the heterogeneity of etiology is also discussed. For NF2 patients, no specific data are available; the current knowledge comes from series of NF2 patients for which seizures has revealed the disease or from isolated case reports of tumors associated with seizures. CONCLUSION: Cryptogenic epilepsy without anatomic defect is likely to be related to NF1, while seizures seem to be secondary to leptomeningeal tumors (meningioma, meningioangiomatosis) in NF2 patients. PMID- 22041821 TI - Neurosyphilis is a treatable cause of dementia not systematically searched for, but still worth to be considered. PMID- 22041822 TI - Metronidazole-cerebellopathy associated with peripheral neuropathy, downbeat nystagmus, and bilateral ocular abduction deficit. PMID- 22041823 TI - [Neuralgic amyotrophy revealed by diaphragmatic palsy]. AB - INTRODUCTION: Neuralgic amyotrophy is considered to be a form of mononeuropathy multiplex which generally involves the nerves of the upper limbs. OBSERVATIONS: We describe four cases of neuralgic amyotrophy revealed by dyspnea due to phrenic nerve involvement, with asymptomatic motor deficit in the upper part of the brachial plexus. CONCLUSION: Phrenic nerve involvement revealed by dyspnea is rare. Associated with neurologic signs, the diagnosis is evocative. In case of an isolated attack, the key to diagnosis is the electromyographic exam. PMID- 22041824 TI - [Psychiatric and cognitive signs associated with inborn errors of metabolism]. AB - BACKGROUND: Inborn errors of metabolism are rare disease and forms with presenting psychiatric signs are even rarer. However, some of them are treatable and early treatment (which may start when psychiatric signs are the only manifestation) may lead to more efficacy and better improvement for either psychiatric and organic signs. Recognition by psychiatrist, and non-specialized practionners, is therefore a major issue for patients and health care. OBSERVATION: After an illustrating case report, we propose a short description of psychiatric signs, focusing on presenting signs, associated with neurometabolic disease. We also propose a pragmatic and simple clinical diagnostic strategy for practionners when facing to atypical psychiatric signs leading to a minimum reasonable exploratory assessment. CONCLUSION: Atypical psychiatric signs must be known by psychiatrists in order to seek neurometabolic disease. Multidisciplinary approach, especially between psychiatrists and neurologists, is crucial in this topic. PMID- 22041825 TI - [Working memory in multiple sclerosis: a review]. AB - INTRODUCTION: Impairment of working memory (WM) is frequently reported in multiple sclerosis (MS) patients. However, the various methodologies used, as well as the populations selected for study, hinder the interpretation of results. The aim of this study is to propose a review about WM in MS. METHOD: Twenty studies have presented results on WM with neuropsychological assessment. RESULTS: All studies conclude that WM is impaired in MS. Reduced processing speed would be central, with major impact on WM performance. According to Baddeley's model, difficulties may be located at the level of the central executive. MS patients would be sensitive to tasks with a high cognitive load. However, performances seem to become better when the processing speed is adapted. Explanatory models relating to this kind of impairment have been proposed from imaging studies. Compensation could mask deficits in WM at the early stage of the disease, but would become blurred with advancing illness and increasing load required for the task. CONCLUSIONS/PROSPECTS: In order to assess WM, adapted tools should be proposed to MS patients. Focus should be placed on processing speed. Further studies are needed, for instance to examine the dissociation of the processes operating within the central executive as described in Miyake's model. Imaging investigations have provided essential data helpful for understanding compensation mechanisms. These data should be useful for developing adapted remediation plans to compensate for the crippling impairment observed in everyday life. PMID- 22041826 TI - The evolving role of surgeons and surgery in the changing NHS. PMID- 22041828 TI - Core Training: evidence-based medicine for doctors in training. PMID- 22041827 TI - Rivaroxaban: direct factor Xa inhibition to treat acute deep vein thrombosis. PMID- 22041829 TI - Preventing acute kidney injury: identifying risk and reducing injury. PMID- 22041830 TI - Renal failure in chronic liver disease and the hepatorenal syndrome. PMID- 22041831 TI - Medical management of renal stone disease. PMID- 22041832 TI - Venous complications of thoracic outlet syndrome. PMID- 22041833 TI - Anaesthesia in obese patients. PMID- 22041834 TI - How to self train in basic laparoscopic skills. PMID- 22041835 TI - Clinical leadership: the challenge for senior leaders. PMID- 22041836 TI - Removal of a titanium alloy ring. PMID- 22041837 TI - Conn's syndrome unmasked by thiazide-induced hypokalaemia. PMID- 22041839 TI - Dissecting thoracic aneurysm: an unusual presentation. PMID- 22041838 TI - Hepatorenal syndrome precipitated by infective endocarditis. PMID- 22041841 TI - Teaching of anatomy through cadaveric dissection: are we really satisfied? PMID- 22041842 TI - The increasing cost of education. PMID- 22041844 TI - Perioperative epidurals: the controversy goes on. PMID- 22041845 TI - Immunocytochemical studies on the effect of 405-nm low-power laser irradiation on human-derived A-172 glioblastoma cells. AB - The application of low-power laser irradiation (LLI) affects the cell cycle and cell proliferation in various kinds of cells. LLI at a wavelength of 808 nm and a power of 30 mW has been found to significantly decrease the proliferation rate of cells of the human-derived glioblastoma cell line A-172. To determine if this effect of LLI is specific to 808-nm LLI, the present study was designed to reveal the effects of 405-nm LLI under the same experimental conditions. A-172 glioblastoma cells were cultured in 96-well plates according to the conventional protocol. Two different schedules of 405-nm LLI (27 mW) were tested: longer periods of 20, 40 and 60 min and shorter periods of 1, 2, 3, 5, 10 and 15 min. Cells on a digital image displayed on a computer monitor were counted and the proliferation ratio was determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl-2H-tetrazolium bromide) staining. Annexin-V-FLUOS staining and acridine orange/ethidium-bromide staining were in an immunocytochemical assay to determine if cells were viable or dead (due to apoptosis or necrosis). Cell counting and MTT staining showed that longer 405-nm LLI significantly suppressed the proliferation of A-172 cells at 48 h after LLI (p < 0.05 or p < 0.01) and that the effect of LLI tended to be dose-dependent with morphological changes including cell death. At 90 min after LLI, shorter 405-nm LLI caused necrotic as well as apoptotic cell death, and these effects depended on irradiation time, power and energy density. Detailed analysis revealed that this lethal effect occurred after LLI and was not sustainable. It is concluded that 405-nm LLI has a lethal effect on human-derived glioblastoma A-172 cells, that is different from the suppressive effect without morphological changes induced by 808-nm LLI. PMID- 22041846 TI - Patient responses to Er:YAG laser when used for conservative dentistry. AB - The utilization of laser technology in conservative dentistry offers several advantages compared with traditional instruments, but one of the still unsolved problems is the difficulty in describing and explaining these advantages to patients. The aims of this study were to verify the efficacy of the way patients are informed and to evaluate their satisfaction with laser-assisted treatment. Before treatment, 100 patients were given a brochure that explained the relevant laser-assisted dental procedures, and after dental treatment an 11-item questionnaire was administered to the patients to evaluate their satisfaction with the treatment. Statistical analysis showed high levels of satisfaction for all the questions, especially those regarding the choice between laser therapy and traditional instruments (100%), choosing laser in the future (89%), and recommending it to family and friends (84%). This study may be relevant when determining the overall satisfaction of patients with this new technology. PMID- 22041847 TI - Air movements interfere with laser speckle contrast imaging recordings. PMID- 22041848 TI - Punctal occlusion is safe and efficient for the treatment of keratoconjunctivitis sicca in patients with ocular GvHD. AB - The use of punctal plugs in the treatment of keratoconjunctivitis sicca (KCS) in inflammatory eye disease remains controversial because of the potentially increased retention time of tears enriched with inflammatory cytokines that may aggravate eye inflammation. We describe the safety and efficacy of punctal occlusion in a retrospective analysis of 19 patients (16 men) with KCS due to chronic GvHD (cGvHD). Efficacy and safety were assessed by subjective and objective criteria (symptoms, corneal fluorescein staining, tear film break-up time (BUT), Schirmer I test, Jones test and visual acuity). Follow-up was from plug insertion until maximum one year after punctal occlusion. After punctal occlusion, patients reported a significant increase in subjective comfort (1.10 vs 0.59 on a scale ranging from no symptoms (0) to severe impairment (2), P<0.001). Pathological corneal fluorescein staining decreased significantly (P<0.001) and tear film BUT remained unchanged (5.98 vs 4.0 s, P=0.79). Measurement of tear secretion or retention time showed a non-significant trend for improvement in the Schirmer I (3.0 vs 3.40 mm, P=0.08) and Jones (1.36 vs 2.8 mm, P=0.08) tests. The logMAR visual acuity remained unchanged. Punctal occlusion achieved a significant improvement in subjective symptoms and objective findings in ocular GvHD without increasing ocular inflammation. PMID- 22041849 TI - Indolent T-cell large granular lymphocyte leukaemia after haematopoietic SCT: a clinicopathologic and molecular analysis. AB - Four women and three men after allogeneic (n=4) and autologous (n=3) haematopoietic SCT (HSCT) were observed to have an increase in T-cell large granular lymphocytes (T-LGLs) of CD3+CD8+ phenotype for a median of 41 (15-118) months. Clonal rearrangement of the T-cell receptor gene was verified by two PCR techniques and direct DNA sequencing, confirming that the cases were neoplastic and therefore classifiable as T-LGL leukaemia. In the allogeneic HSCT cases, T LGL leukaemia was derived from donor T cells in three patients, as shown by DNA chimerism analysis, and recipient T cells in one patient who had graft failure previously. None of the patients showed cytopenia, autoimmune phenomenon or organ infiltration, which were features typical of de novo T-LGL leukaemia. Six patients had remained asymptomatic with stable large granular lymphocyte counts. One patient died from cerebral relapse of the original lymphoma. T-LGL leukaemias occurring post-HSCT are distinct from de novo T-LGL leukaemia and may have a different pathogenesis and clinical course. Patients did not require specific treatment, and the disease remained stable for long periods. PMID- 22041850 TI - Factors associated with the efficiency of PBSC collection in POEMS syndrome patients undergoing autologous PBSC transplantation. PMID- 22041851 TI - Differences in mothers' and fathers' psychological distress after pediatric SCT: a longitudinal study. AB - The purpose of this study was to examine longitudinally psychological distress and its correlates in mothers and fathers of children who undergo SCT, up to 2 years post SCT. A total of 111 parents of patients diagnosed mainly with leukemia completed standardized measures of depression and anxiety symptoms as indicators of psychological distress, 85 at 1 year pre-SCT and 81 at 2 years post SCT. Parents' age and gender, child's age, diagnosis, radiation history, behavior and physical health were examined as potential related factors. Linear mixed models for repeated measures with appropriate covariance structure were used in the analysis. Depression and anxiety scores significantly decreased by 2 years for mothers and fathers. Mothers reported significantly more depression symptoms than did fathers, but reported comparable symptoms of anxiety. Pre-SCT depression and anxiety scores, mother's age (younger), child's behavior problems, radiation history and diagnosis of neuroblastoma predicted maternal distress 2 years post SCT; pre-SCT depression and anxiety scores, father's age (older) and child's diagnosis predicted father's distress. This study highlights differences and similarities in mothers' and fathers' psychological distress and identifies related risk factors. The results can guide interventions for mothers and fathers whose children undergo SCT based on their pre-SCT psychosocial risk. PMID- 22041852 TI - Subset characterization of myeloid-derived suppressor cells arising during induction of BM chimerism in mice. AB - To date, myeloid-derived suppressor cells (MDSC) have been best studied in cancer, where they represent an escape mechanism for immune surveillance. MDSC are now also gaining interest in the context of transplantation. Suppressive CD11b(+) myeloid progenitor cells have been reported to expand endogenously during BM chimerism induction in mice; in particular, in irradiated MHC-matched BM chimeras and in parent-in-F1 BM chimeras. Myeloid cell expansion coincided with a time frame where donor lymphocyte infusion (DLI) therapy-mediated GVL effects without GVHD. Hypothesizing that regulatory myeloid cells may have a role in regulating post-transplant T-cell alloreactivity, we performed a detailed phenotypic and functional characterization of these cells in the parent-in-F1 C57BL/6 -> [C57BL/6xDBA2] model. We found that transiently expanding CD11b(+) myeloid progenitor cells comprise the two phenotypically and functionally distinct mononuclear and polymorphonuclear MDSC subsets that were recently described in tumor-bearing mice. Both MDSC subsets suppressed in vitro and in vivo alloreactive T-cell proliferation. Also, both the subsets mediated enhanced in vitro suppression when harvested from chimeras, given a prior in vivo challenge with non-tolerant donor T cells, indicating that allo-activated T cells can activate MDSC in vivo. This study provides the basis to investigate the potentially beneficial-role of expanding MDSC in influencing the risk of GVHD during chimerism induction. PMID- 22041853 TI - Opportunistic screening of hospital staff using primary colonoscopy: participation, discomfort and willingness to repeat the procedure. AB - BACKGROUND: Participation in and tolerability of primary colonoscopy screening are presumed to be relatively low. The present study aimed to test its feasibility in a well-informed population of hospital staff using an intensive information campaign, and to identify factors associated with screening colonoscopy rated as uncomfortable. METHODS: Data were collected using standardized forms. RESULTS: Out of 1,090 invited employees (50-65 years), 447 (41.0%) participated. Bowel preparation and colonoscopy were rated as 'somewhat to very uncomfortable' by 79.5 and 21.9%, respectively. 96.3% of participants were willing to repeat colonoscopy in the future. Participants rating colonoscopy as uncomfortable were more likely unwilling to repeat the procedure (OR 8.026, CI 2.667-24.154). Multivariate analysis (age- and gender-adjusted) showed an association of colonoscopy rated as uncomfortable with: abdominal pain during colonoscopy (OR 3.185, CI 1.642-6.178), other pain (OR 2.428, CI 1.335-4.416), flatulence (OR 2.175, CI 1.219-3.881), embarrassment (OR 2.843, CI 1.350-5.989), abdominal pain after colonoscopy (OR 1.976, CI 1.041-3.751), and a prolonged procedure time (OR 1.000, CI 1.000-1.001). CONCLUSIONS: Acceptance of primary colonoscopy screening for colorectal neoplasia was high, although participants with symptoms during and after colonoscopy were more likely to rate colonoscopy as uncomfortable. This type of opportunistic screening procedure is suitable for the introduction of screening programs and may be useful in areas that have no access to population-based screening. PMID- 22041854 TI - Hollow mesoporous zeolite microspheres: hierarchical macro-/meso-/microporous structure and exceptionally enhanced adsorption properties. AB - We report the synthesis of a new kind of uniform hollow zeolite microspheres with hierarchical macro-/meso-/microporosity by an efficient strategy combining bi templating, steam-assisted crystallization and then a mild alkaline etching method. This novel product has a hollow architecture, highly crystallized zeolite shells and more importantly, high dye adsorption capabilities. PMID- 22041855 TI - Eligibility, compliance and persistence of sequential therapy with aromatase inhibitors following 2-3 years of tamoxifen in endocrine adjuvant breast cancer therapy. AB - OBJECTIVE: This study evaluated the eligibility, compliance and persistence of sequential therapy, i.e. a switch to an aromatase inhibitor (AI) following 2-3 years of tamoxifen, in adjuvant endocrine breast cancer (BC) treatment. METHODS: Data concerning 388 BC patients (age <=70 years) who started endocrine adjuvant therapy between 1998 and 2008 were analyzed. RESULTS: From the 263 patients who started therapy with tamoxifen, 167 (63.5%) were eligible for a sequential therapy. Fifty-nine patients (35.3%) were offered a switch by their physicians; women who had their follow-up at oncological units received the offer more often when compared to those treated by general practitioners (p < 0.001). Out of these 59 patients, 50 followed the proposal (compliance 84.7%). Of those who agreed to a sequential therapy, 2 (4%) were non-persistent to endocrine therapy; in 9 cases (18.0%), a re-switch to tamoxifen was done due to AI-related adverse side effects. CONCLUSIONS: Only a minority of the patients who started an endocrine adjuvant BC therapy was eligible for sequential therapy. Patients who underwent a switch had a high rate of persistence. Efforts should be made to make sure that all physicians, above all general practitioners, who are involved in the treatment of BC patients, are provided with current therapy guidelines. PMID- 22041856 TI - Twin epidemics: asthma and obesity. PMID- 22041857 TI - Clinical usefulness of CEA, CA19-9, and CYFRA 21-1 as tumor markers for urothelial bladder carcinoma. AB - OBJECTIVE: To evaluate the usefulness of measuring serum CEA, CA19-9, and CYFRA 21-1 levels for the diagnosis and monitoring of bladder cancer. MATERIALS AND METHODS: Serum levels of CEA, CA19-9, and CYFRA 21-1 were measured in 85 patients with bladder cancer. The absolute level of each marker and the positive rate were compared with the clinical stage and histological grade of the tumor. Changes of the markers were assessed in patients with or without disease progression, and the correlations between survival and positivity/negativity of these markers were also evaluated. RESULTS: A higher serum level of CYFRA 21-1 was significantly correlated with higher tumor stage (p < 0.01) and higher grade (p < 0.05). In contrast, serum CEA and CA19-9 levels did not differ significantly among each stage and grade. The CYFRA 21-1 level increased significantly along with disease progression (from 7.33 +/- 13.3 to 55.9 +/- 127 ng/ml, p < 0.01). Patients who were positive for CYFRA 21-1 had significantly worse disease-specific survival (p < 0.0001, log rank test). CONCLUSION: Serum CYFRA 21-1 seems to be a marker of advanced- and high-grade urothelial carcinoma of the bladder. It is useful for monitoring this disease and for predicting the prognosis. In contrast, the clinical usefulness of CEA and CA19-9 as tumor markers was not demonstrated. PMID- 22041858 TI - Titanium preferential binding sites in human serum transferrin at physiological concentrations. AB - Serum transferrin (Tf) is an iron binding glycoprotein that plays a central role in the metabolism of this essential metal but it also binds other metal ions. Four main transferrin forms containing different iron binding states can be distinguished in human serum samples: monoferric (C-site or N-site), holotransferrin (with two Fe atoms) and apotransferrin (with no metal). Recently, it has been reported that Tf binds also Ti even more tightly than does Fe, in artificially Ti(iv) spiked solutions. However, very limited work has been done on the Ti binding to Tf at physiological concentrations in patients carrying intramedullary Ti nails. Here we report the chemical association of Ti to Tf "in vivo" under different chromatographic conditions by elemental mass spectrometry using double focusing inductively coupled plasma (DF-ICP-MS) as detector. For the separation of the Ti/Fe-Tf forms different gradient conditions have been explored. The observed results reveal that human serum Ti (from patients carrying intramedullary Ti nails) is uniquely associated to the N-lobe of Tf. The investigation of the influence of sialic acid in the carbohydrate chain of human serum Tf, studied by incubating the protein with neuraminidase (sialidase) to obtain the monosialilated species, revealed that the binding affinity of Ti was similar for monosialo-Tf and for native-Tf and occurs in the N-lobe. These results suggest that the species Fe(C)Ti(N)-TF might provide a route for Ti entry into cells via the transferrin receptors after the release of the metal from its implants. PMID- 22041859 TI - Visible-light photoredox catalyzed oxidative Strecker reaction. AB - An aerobic photocatalytic oxidative cyanation of tertiary amines providing valuable alpha-aminonitriles in good to excellent yields was developed. Mild reaction conditions and low catalyst loading are attractive features of the protocol. PMID- 22041862 TI - Functionalized 2,3-dihydrofurans via palladium-catalyzed oxyarylation of alpha allyl-beta-ketoesters. AB - The palladium-catalyzed reaction of (hetero)aryl bromides, chlorides, and nonaflates with alpha-allyl-beta-ketoesters provides ready efficient access to functionalized 2,3-dihydrofurans. The reaction tolerates several useful substituents including chloro, fluoro, ether, ketone, ester, cyano, and nitro groups. PMID- 22041865 TI - IL-31 expression by inflammatory cells is preferentially elevated in atopic dermatitis. AB - Interleukin-31 (IL-31) is a recently discovered cytokine expressed in many human tissues, and predominantly by activated CD4(+) T cells. IL-31 signals through a heterodimeric receptor consisting of IL-31 receptor alpha (IL-31RA) and oncostatin M receptor beta (OSMR). Earlier studies have shown involvement of IL 31 and its receptor components IL-31RA and OSMR in atopic dermatitis, pruritus and Th2-weighted inflammation at the mRNA level. The aim of this study was to investigate IL-31 protein expression in skin of such conditions. Immunohistochemical staining for IL-31, IL-31RA and OSMR was performed in formalin-fixed paraffin-embedded biopsy specimens. IL-31 expression was increased in the inflammatory infiltrates from skin biopsies taken from subjects with atopic dermatitis, compared with controls (p <= 0.05). IL-31, IL-31RA and OSMR protein immunoreactivity was not increased in biopsies from subjects with other Th2-weighted and pruritic skin diseases. Our results confirm, at the protein level, the relationship between IL-31 expression and atopic dermatitis. Our results do not support a general relationship between expression of IL-31/IL-31R and pruritic or Th2-mediated diseases. PMID- 22041864 TI - Decreased serum sclerostin levels in patients with primary hyperparathyroidism: a cross-sectional and a longitudinal study. AB - Decreased serum sclerostin was evident in patients with primary hyperparathyroidism and was inversely related to parathyroid hormone (PTH). Sclerostin normalized earlier than biochemical bone turnover markers (BTMs) following parathyroidectomy. INTRODUCTION: There is limited information on the changes of serum sclerostin in conditions with chronic PTH excess in humans. The main objectives of the present study were to: (1) examine cross-sectionally the changes of serum sclerostin levels in patients with primary hyperparathyroidism (PHPT), (2) study the time course changes in serum sclerostin in PHPT patients following parathyroidectomy (PTX) followed up longitudinally for 12 months, and (3) compare the changes in serum sclerostin to that of BTMs. METHODS: We studied 60 PHPT patients and compared them with 74 PTX patients together with 268 age- and sex-matched healthy controls. Also, we followed 27 PTX patients longitudinally at 2, 4, 6, 10, 30, 60, 180, and 360 days postoperatively. Serum sclerostin, BTMs, and minerals were measured. Also, bone mineral density was determined by dual energy X-ray absorptiometry. RESULTS: Patients with PHPT exhibited significantly lower mean serum sclerostin [mean, in picomoles per liter; 95% confidence interval (CI)] (28.98; 27.94-30.03) than that obtained for PTX patients (37.01; 35.75-38.27) and healthy controls (46.22; 45.13-47.31) (P < 0.0001, for each case), respectively. Serum PTH inversely correlated with serum sclerostin (r = -0.651, P < 0.0001). Serum sclerostin was normalized in PTX patients by the tenth day postoperatively and remained within the expected reference range thereafter. CONCLUSIONS: Significantly decreased serum sclerostin was evidenced in PHPT patients as compared with PTX and euparathyroid controls. The inverse PTH and sclerostin relationship suggests that sclerostin is downregulated by PTH in humans. Serum sclerostin normalized earlier than BTMs following parathyroidectomy. PMID- 22041866 TI - Multicenter, randomized study of genetically modified recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in cancer patients receiving chemotherapy. AB - PURPOSE: The aim of this study is to evaluate the efficacy and safety of genetically modified recombinant human IL-11 (mIL-11), using original IL-11 as an active control, in a multicenter randomized trial involving 88 cancer patients undergoing chemotherapy METHODS: Eighty-eight subjects who had platelets <= 75 * 10(9)/L during the prior chemotherapy were randomized to the MR or RM group. Cohort MR consists of subcutaneous injection of mIL-11 (7.5 MUg/kg/day) for 10 days, beginning 72 h after chemotherapy for a 21-day chemotherapy cycle (cycle-1) followed by that of recombinant human interleukin-11 (rhIL-11) (25 MUg/kg/day) for another 10 days (cycle-2). Cohort RM represents the reverse sequence. Intent to-treat populations of mIL-11 (n = 73) or rhIL-11 (n = 80) were analyzed to evaluate the safety. RESULTS: The incidence of drug-related adverse events of mIL 11 (32.9%) was lower than that of rhIL-11 (51.3%) (p = 0.033). There were no unexpected >= grade-3 adverse events, and no subject developed antibodies to the mIL-11 protein. Sixty-two subjects were analyzed for efficacy by measuring average platelet levels. Both mIL-11 and rhIL-11 increased nadir platelet levels (62.6 +/- 34.9 * 10(9)/L for mIL-11 vs. 60.2 +/- 31.7 * 10(9)/L for rhIL-11) as compared with the untreated control group (41.2 +/- 17.7 * 10(9)/L) (p < 0.0001). There was no statistical difference in average platelet levels and platelet recovery rate between mIL-11 and rhIL-11. CONCLUSIONS: This study shows that mIL 11 is well tolerated and has thrombopoietic activity equivalent to one third of the clinical dose of rhIL-11, indicating the potential of mIL-11 for use in the treatment of CIT. PMID- 22041867 TI - Small cell carcinoma arising from the bulbar urethra: a case report and literature review. AB - Primary neuroendocrine carcinomas of the genitourinary tract are rare and aggressive tumors carrying a bad prognosis. With squamous cell and transitional cell carcinoma being the most commonly reported urethral malignancies, primary small cell carcinoma (SCC) of the urethra is extremely rare. To date, only 5 cases have been reported in the literature. We present the first case of primary SCC occurring in the bulbar urethra in an 89-year-old male. We discuss the clinical, histological and immunohistochemical features of SCC of the urethra. Furthermore, we summarize the available literature and discuss the possible treatment options for this rare yet aggressive neoplasm. PMID- 22041868 TI - The efficiency of micrometastasis by sentinel node navigation surgery using indocyanine green and infrared ray laparoscopy system for gastric cancer. AB - BACKGROUND: The clinical application of sentinel node navigation surgery (SNNS) for patients with gastric cancer requires accurate intraoperative diagnosis of lymph node metastasis. However, the clinical significance of the diagnosis of lymph node micrometastasis for gastric cancer has not been established. In this study, we evaluated lymph nodes dissected during SNNS by immunohistochemistry with anti-cytokeratin antibody (IHC) staining for gastric cancer to investigate the usefulness of SNNS. PATIENTS AND METHODS: The subjects were 130 patients with gastric cancer (3,381 lymph nodes) who underwent SNNS with infrared ray observation and lymph node dissection of D1+alpha or more. The dissected lymph nodes were stained with IHC (CAM 5.2), and the results were compared with intra- and postoperative diagnoses by hematoxylin and eosin (H&E) staining. In addition, the association of metastatic lymph nodes and ICG-positive lymph nodes was examined. RESULTS: The number of patients (lymph nodes) with lymph node metastasis by HE and IHC staining was 16 (52 nodes) and 31 (91 nodes), respectively. Fifteen patients (27 nodes) diagnosed with pN0 by HE staining were diagnosed to be metastatic by IHC staining. The tumor depth of these patients was pT1 in ten patients (m, 3; sm, 7) and pT2 in five (mp, 4; ss, 1). Regarding the histological type, three patients were classified as well-differentiated type, while six patients each had moderately and poorly differentiated types. The grade of lymphatic invasion was ly0 in 5, ly1 in 6, and ly2 in 4, respectively. Histological assessment of 27 IHC-positive and HE-negative cells indicated 5 single cells, 16 clusters, and 6 micrometastases. These lymph nodes were all included in the sentinel nodes (SN) identified during surgery. All but one patient (0.8%) were recurrence-free at 2-8 years after surgery (median 74.7 months). The one patient developed anastomotic recurrence 4.5 years after the first operation and died. CONCLUSION: Since all 27 lymph nodes in 15 patients with metastasis by IHC staining but not by HE staining were micrometastasis or less and included in the SN, ICG-positive lymphatic basin dissection by SNNS with infrared ray observation seems to be an adequate method of lymph node dissection for gastric cancer. PMID- 22041870 TI - Gender differences in examinee performance on the Step 2 Clinical Skills data gathering (DG) and patient note (PN) components. AB - Multiple studies examining the relationship between physician gender and performance on examinations have found consistent significant gender differences, but relatively little information is available related to any gender effect on interviewing and written communication skills. The United States Medical Licensing Examination (USMLE) Step 2 Clinical Skills (CS) examination is a multi station examination where examinees (physicians in training) interact with, and are rated by, standardized patients (SPs) portraying cases in an ambulatory setting. Data from a recent complete year (2009) were analyzed via a series of hierarchical linear models to examine the impact of examinee gender on performance on the data gathering (DG) and patient note (PN) components of this examination. Results from both components show that not only do women have higher scores on average, but women continue to perform significantly better than men when other examinee and case variables are taken into account. Generally, the effect sizes are moderate, reflecting an approximately 2% score advantage by encounter. The advantage for female examinees increased for encounters that did not require a physical examination (for the DG component only) and for encounters that involved a Women's Health issue (for both components). The gender of the SP did not have an impact on the examinee gender effect for DG, indicating a desirable lack of interaction between examinee and SP gender. The implications of the findings, especially with respect to the validity of the use of the examination outcomes, are discussed. PMID- 22041869 TI - The flow angle beneath the gastrojejunostomy predicts delayed gastric emptying in Roux-en-Y reconstruction after distal gastrectomy. AB - BACKGROUND: Delayed gastric emptying without mechanical obstruction after Roux-en Y reconstruction has been defined as Roux stasis syndrome. It occurs in 10-30% of patients after such reconstruction. So far, the cause of this stasis has not been completely identified. This study aimed to reduce Roux stasis using surgical techniques. METHODS: From November 2007 to October 2010, we performed 101 distal gastrectomies with Roux-en-Y reconstruction. All the gastrojejunostomies were performed with end-to-end anastomoses. Roux stasis was analyzed with respect to tumor location, extent of the dissection, tumor progression, operation time, antecolic/retrocolic reconstruction, and the shape of the gastrojejunostomy. The shape of the gastrojejunostomy was evaluated by contrast gastroradiography 4 days after the operation. RESULTS: Roux stasis syndrome was observed in 17 of the 101 patients. There was no relationship between the extent of the dissection, tumor progression, or operation time and the occurrence of Roux stasis. There was no difference in the incidence of Roux stasis between antecolic and retrocolic reconstructions. However, the group that displayed a straight anastomotic shape on contrast radiography demonstrated an apparently lower incidence of Roux stasis (p = 0.0003). In addition, Roux-en-Y reconstruction following gastric cancer was more frequently followed by Roux stasis in the antrum than in the midstomach (p = 0.0036). Cases of Roux stasis occurred 11.8 days after surgery on average and resolved within 2 weeks on average. CONCLUSIONS: Our findings demonstrate the substantial benefits of a straight anastomosis of the gastrojejunostomy for the prevention of Roux stasis syndrome. PMID- 22041871 TI - Student perceptions of the progress test in two settings and the implications for test deployment. AB - BACKGROUND: The Progress Test (PT) was developed to assess student learning within integrated curricula. Whilst it is effective in promoting and rewarding deep approaches to learning in some settings, we hypothesised that implementation of the curriculum (design and assessment) may impact on students' preparation for the PT and their learning. Aim To compare students' perceptions of and preparations for the PT at two medical schools. METHOD: Focus groups were used to generate items for a questionnaire. This was piloted, refined, and then delivered at both schools. Exploratory factor analysis identified the main factors underpinning response patterns. ANOVA was used to compare differences in response by school, year group and gender. RESULTS: Response rates were 640 (57%) and 414 (47%) at Schools A and B, respectively. Three major factors were identified: the PT's ability to (1) assess academic learning (2) support clinical learning; (3) the PT's impact on exam preparation. Significant differences were found between settings. In the school with early clinical contact, more frequent PTs and no end of unit tests, students were more likely to appreciate the PT as a support for learning, perceive it as fair and valid, and use a deeper approach to learning but they also spent longer preparing for the test. CONCLUSION: Different approaches to the delivery of the PT can impact significantly on student study patterns. The learning environment has an important impact on student perceptions of assessment and approach to learning. Careful decisions about PT deployment must be taken to ensure its optimal impact. PMID- 22041872 TI - Performance of fluorodeoxyglucose-positron-emission tomography/computed tomography for evaluating tumor response to nonsurgical treatment. PMID- 22041873 TI - Applications of statistics to medical science (1) Fundamental concepts. AB - The conceptual framework of statistical tests and statistical inferences are discussed, and the epidemiological background of statistics is briefly reviewed. This study is one of a series in which we survey the basics of statistics and practical methods used in medical statistics. Arguments related to actual statistical analysis procedures will be made in subsequent papers. PMID- 22041874 TI - Pathophysiology of functional dyspepsia. AB - Functional dyspepsia is a highly prevalent and heterogeneous disorder. Functional dyspepsia involves many pathogenic factors, such as gastric motility disorders, visceral hypersensitivity, psychological factors, Helicobacter pylori infection, and excessive gastric acid secretion. The present article provides an overview of pathogenetic factors and pathophysiologic mechanisms. PMID- 22041875 TI - Microinjection of different doses of corticotropin-releasing factor into the medial prefrontal cortex produces effects opposing anxiety-related behavior in rats. AB - Corticotropin-releasing factor (CRF) in the medial prefrontal cortex (mPFC) is suggested to play an important role in mediating fear, anxiety, and depression. The results of the studies of the actions of CRF in the mPFC regarding anxiety related behavior, however, seem contradictory. In one study, microinjection of CRF into the mPFC produced an increase in anxiety-related behavior on the elevated plus maze, whereas in another study CRF produced an anxiolytic-like effect. To test whether the different doses of CRF used in these experiments are responsible for the differing results, we examined the dose-dependent effects of CRF (0.015, 0.05, 0.15, 0.5, and 1.0 ug/0.5 uL/site) microinjected into the bilateral mPFC of male Wistar rats on anxiety-related behavior in the elevated plus maze. We found that microinjection of 0.05 ug CRF significantly decreased the number of open-arm entries, whereas 1.0 ug CRF significantly increased the time spent on the open arms. The results indicate that CRF has effects opposing anxiety-related behavior in the elevated plus maze: anxiety-related behavior at a lower dose and an anxiolytic-like effect at a higher dose. PMID- 22041876 TI - Use of ultrasonic cleansing in managing the couplers of dialyzer systems. AB - Dialysis-related complications have become a major concern as the number of patients receiving long-term maintenance dialysis increases. One cause of complications is contamination of the dialysis fluid. When dialysis fluid contaminated by bacteria or endotoxin (ET) or both has been used for a long time, cytokine production in vivo is enhanced and can lead to such complications as dialysis amyloidosis. The rate of dialysis-related complications might be reduced with a hemopurification method that uses a large amount of dialysis fluid as a substitution fluid (on-line hemodiafiltration) or an efficient dialyzer with enhanced internal filtration in which the dialysis fluid returns to the body as a replacement fluid; however, at the same time, there is an increased risk of ET entering the body because the dialysis fluid might be contaminated. Therefore, the dialysis fluid must be made aseptic, and the dialysis fluid line must be properly managed to prevent contamination of the dialysis fluid. A half-opened line is at great risk of contamination by living microbes, which can grow in dead spaces and where the flow of dialysis fluid is interrupted. The management of couplers is an important measure for maintaining cleanliness at the end of the dialysis fluid flow. We attempted to separate and regularly clean the main body of the coupler with ultrasonic equipment as a method of managing the conventional coupler. Using improved types of coupler, the water quality of the postcoupler flow was maintained at a level as high as that of the precoupler flow for the duration of the evaluation period without separate cleansing being done. Although separate once-a-week cleansing of the conventional coupler was able to keep ET values less than the detection limit, viable cell counts were unstable. On the other hand, twice-a-week ultrasonic cleansing eliminated almost all viable cells. No definite difference in ET values or viable cell counts was found between the cleansing groups, and ultrasonic cleansing was able, by itself, to provide a sufficient cleansing effect. We conclude that ultrasonic cleansing of conventional couplers is a useful method for maintaining the water quality of the postcoupler flow because the cleansing of the coupler twice or more a week is sufficient to keep the water quality of the postcoupler flow as high as that of the precoupler flow. PMID- 22041877 TI - Autopsy cases of miliary tuberculosis: clinicopathologic features including background factors. AB - To assist physicians, especially young physicians, in identifying tuberculosis (TB) infection before the terminal stage, we analyzed 7 cases of numerous tuberculous granulomas in multiple organs and compared clinical and autopsy findings between cases. Patients ranged in age from 41 to 86 years at the time of death. The main chief complaint was fever of unknown origin (3 of 7 cases [43%]). The main underlying conditions were liver cirrhosis (2 of 7 cases [29%]) and chronic renal failure (2 of 7 cases [29%]). Two patients (29%) had been given methylprednisolone pulse therapy for various lung disorders. Active TB was not diagnosed before autopsy in 4 of 7 (57%) patients. Calcified lesions indicative of old TB were present in 4 of 7 (57%) patients. Thus, miliary tuberculosis may represent a re-emergence of latent TB infection in these cases. Various histologic features of nonreactive exudative inflammation were seen, along with granulomas containing Langhans giant cells with or without caseous necrosis in hypervascular organs, such as the lung, liver, and bone marrow. Physicians should be mindful of the possibility of miliary TB when older patients with hepatorenal disease and a history of TB infection have undergone immunosuppressive treatment. Active tuberculous infection can depend on the presence of an underlying disease and immunocompromise. PMID- 22041878 TI - Intracystic hemorrhage required no treatment from one of multiple hepatic cysts. AB - We describe a patient with intracystic hemorrhage from one of multiple hepatic cysts. A 66-year-old woman was admitted to Nippon Medical School Hospital because of pain in the right upper quadrant of the abdomen. The medical history included multiple hepatic cysts and angina pectoris, which had been treated with aspirin. Three weeks before presentation, pain occurred in the right upper quadrant of the abdomen but resolved spontaneously. Ultrasonography revealed multiple hepatic cysts. One of the cysts in segment 8 had a hypoechoic structure and contained fluid. Computed tomography showed an area of homogenous density (diameter, 6 cm) which was slightly greater than that of the other hepatic cysts in segment 8. There was calcification of the cyst wall. On magnetic resonance imaging, this cyst showed heterogeneous hyperintensity on T1- and T2- weighted sequences which was greater than that of the other hepatic cysts. Intracystic hemorrhage of one of the multiple hepatic cysts was diagnosed. The pain gradually resolved without drainage, embolization, or operation, and the patient was discharged. After discharge, the upper abdominal pain did not recur. On magnetic resonance imaging 14 months later, the cyst showed heterogeneous hyperintensity on T1- and T2- weighted sequences which was less than that on the previous scan. PMID- 22041879 TI - Hepatic angiomyolipoma with a giant hemangioma. AB - Hepatic angiomyolipoma is a rare hepatic mesenchymal tumor. We report a case of hepatic angiomyolipoma that was successfully resected along with a giant hemangioma. A 53-year-old Japanese woman was admitted to our hospital for further evaluation of a liver tumor in segment 4. The tumor was detected on positron emission tomography during a health check-up. Abdominal ultrasonography revealed a well-defined mass of mixed echogenicity, 1.5 cm in diameter, in segment 4, and a giant hemangioma of mixed echogenicity, 7 cm in diameter, in segment 7. On enhanced computed tomography, the tumor in segment 4 showed hyperattenuation in the early phase and hypoattenuation in the delayed phase. On magnetic resonance imaging, the tumor in segment 4 showed hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and hyperintensity on diffusion-weighted images. On angiography, the tumor in segment 4 appeared as a circumscribed hypervascular mass in the early phase and a slightly hypovascular mass in the delayed phase. The imaging findings suggested a primary hepatocellular carcinoma. The patient consented to resection of the tumor in segment 4 along with the giant hemangioma in segment 7. These tumors were resected with tumor-free surgical margins by partial resection of segments 4 and 7 of the liver. The cut surface of the resected specimen of segment 4 showed a yellowish tumor consisting of mature adipose tissue. The histopathological diagnoses of the resected specimens were angiomyolipoma in segment 4 and cavernous hemangioma in segment 7. The tumor in segment 4 consisted of mature lipocytes with angiomatous and small lymphocytic components, but no mitotic figures. The tumor showed immunoreactivity to smooth muscle antigen and homatropine methylbromide 45 and no immunoreactivity to AE/E3. The postoperative course was uneventful, and the patient remains well 1 year after the operation. PMID- 22041880 TI - Infantile case of early manifestation of SLE-like symptoms in complete C1q deficiency. AB - C1q deficiency is a rare complement deficiency in the early part of the complement cascade. Patients with C1q deficiency have severe recurring life threatening infections and systemic lupus erythematosus (SLE)-like symptoms. We report on a boy with recurrent life-threatening infections and SLE-like recurrent skin conditions before 2 years of age. Immunological studies revealed an undetectable level of C1q. No abnormality was observed in the urine, but renal biopsy showed segmental granulonephritis. However, the changes observed were atypical for SLE nephritis. This case of C1q deficiency was unusual because the SLE-like symptoms appeared earlier than that normally seen in complement deficiency. Therefore, this case provides insights into the development of autoimmune disease, particularly in the early phase of component deficiency, and in managing renal disease that may develop in the future. PMID- 22041881 TI - Ritodrine-induced pustular eruptions distinctly resembling impetigo herpetiformis. AB - A 27-year-old nulligravida woman without a history of dermatosis was hospitalized for threatened preterm labor at 29 weeks' gestation; therefore, continuous infusion of ritodrine hydrochloride was started. At 31 weeks' gestation, erythematous plaques appeared and spread over the body surface; therefore, a topical steroid preparation was applied. At 32 weeks' gestation, the eruptions developed into irregular annular areas of erythema with multiple pustules accompanied by severe itching, and oral prednisolone treatment was started. Bacterial cultures of the pustules were negative, and a crural cutaneous biopsy revealed Kogoj's spongiform pustules. Based on the clinicopathological findings, the most likely diagnosis was impetigo herpetiformis, which causes cutaneous symptoms closely resembling pustular psoriasis in pregnant females without a history of psoriasis. To rule out ritodrine-induced pustular eruptions, the ritodrine infusion was stopped and treatment with an MgSO(4) preparation was started at 33 weeks' 3 days' gestation; however, the uterine contractions could not be suppressed. Because of the patient's highly edematous, severely painful feet, a cesarean section was performed the same day. Within several days of delivery, the eruptions began to resolve, and no recurrence was observed after treatment with oral prednisolone was stopped 31 days after delivery. On the basis of a positive patch test for ritodrine, we diagnosed pustular drug eruptions caused by ritodrine hydrochloride. Although ritodrine-induced pathognomonic cutaneous eruptions are rare, we would like to emphasize that ritodrine can cause drug-induced pustular eruptions distinctly resembling life-threatening impetigo herpetiformis. PMID- 22041883 TI - Electric-field response of discotic hexabenzocoronene (HBC) liquid crystals. AB - A HBC derivative bearing six branched, space-demanding, alkyl side chains containing ether linkages has been synthesized and its thermotropic properties were investigated by polarization optical microscopy (POM) and differential scanning calorimetry (DSC). To our surprise, this molecule can respond to electric fields, and the influences of alternating current (AC) and directing current (DC) electric field on the assembly of this molecule in liquid crystal cells were discussed. PMID- 22041882 TI - Birth before arrival at a hospital in eastern Tokyo, Japan. AB - Delivery before arrival at a hospital did not cause major perinatal complications; however, it may reflect a serious problem of perinatal medicine in eastern Tokyo, Japan. PMID- 22041884 TI - Structure of salvioccidentalin, a diterpenoid with a rearranged neo-clerodane skeleton from Salvia occidentalis. AB - From the aerial parts of Salvia occidentalis (Labiatae) a new diterpenoid with a rearranged neo-clerodane skeleton was isolated. This new compound was named salvioccidentalin and its structure was established by spectroscopic means. A probable biogenetic relationship with salvigenolide from S. fulgens and salvileucalin A and spiroleucantholide from Salvia leucantha is proposed. PMID- 22041885 TI - Discordant electrical and mechanical atrial delays affect intracavitary electrogram-based cardiac resynchronization therapy optimization. AB - AIMS: It has been shown that atrioventricular (AV) delay optimization improves cardiac resynchronization therapy (CRT) response. Recently, an automatic algorithm (QuickOptTM, St Jude Medical), able to quickly identify the individual optimal AV interval, has been developed. The algorithm suggests an AV delay based on atrial intracavitary electrogram (IEGM) duration. We hypothesized that the difference between electrical and mechanical atrial delays could affect the effectiveness of QuickOpt method. The aim of this study was to test this hypothesis in 23 CRT patients who were recipients of St. Jude Medical devices. METHODS AND RESULTS: Using echocardiography, aortic flow velocity time integral (VTI) was evaluated at baseline, at QuickOpt suggested AV delay and after reducing it by 25 and 50%. Mechanical inter-atrial delay (MIAD) derived from echo/Doppler and electrical inter-atrial delay (EIAD) derived from IEGM were also analysed. Optimal AV delay was identified by the maximal VTI. In 11 patients (Group 1) the maximal VTI was achieved at the AV delay suggested by the algorithm, in 6 patients (Group 2) after a 25% reduction, and in 6 patients (Group 3) after a 50% reduction. While EIAD was similar among the three groups, MIAD was significantly different (P< 0.001). MIAD was longer than EIAD in Group 1 (P= 0.028) and shorter than EIAD in Groups 2 (P= 0.028) and 3. (P< 0.001). Mechanical inter-atrial delay was the only independent predictor of the AV interval associated with the best VTI (R(2) = 0.77; P< 0.001). CONCLUSION: Our results show that MIAD plays the main role in determining the optimal AV delay, thus caution should be taken when optimizing AV by IEGM-based methods. PMID- 22041886 TI - The value of defibrillator far-field electrograms for ablation of idiopathic ventricular fibrillation. AB - We report a case of idiopathic ventricular fibrillation treated by catheter ablation of the monomorphic initiating premature beat. The initiating focus was identified using intacardiac defibrillator electrograms (EGMs). PMID- 22041888 TI - Ligand field-tuned single-molecule magnet behaviour of 2p-4f complexes. AB - Three new 2p-4f complexes of [Ln(acac)(3)(NIT-2Py)].0.5NIT-2Py [Ln(III) = Gd(1), Dy(2)] and [Dy(tfa)(3)(NIT-2Py)].0.5C(7)H(16) (3) (NIT-2Py = 2-(2'-pyridyl)- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; acac = acetylacetonate and tfa = trifluoroacetylacetonate) have been synthesized, and structurally and magnetically characterized. The X-ray structural analysis exhibits that the three complexes show similar mononuclear structures, in which NIT-2Py radical chelates the Ln(III) ion through the oxygen atom of the NO group and the nitrogen atom from the pyridine ring. The static magnetic measurements on the three complexes exhibit ferromagnetic coupling between the lanthanide ion and the radical. Compared to the silence of the out-of-phase ac susceptibility of complex 3, the magnetic relaxation behavior of complex 2 is observed, suggesting single-molecule magnet behavior. The different magnetic relaxation behaviours of 2 and 3 are due to their slightly different crystal structure around the Dy(III) ions. It was demonstrated that the spin dynamic can be modified by the careful adjustment of the ligand field around the metal center. PMID- 22041887 TI - Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells. AB - Here, we show that tamoxifen resistance is induced by cancer-associated fibroblasts (CAFs). Coculture of estrogen receptor positive (ER+) MCF7 cells with fibroblasts induces tamoxifen and fulvestrant resistance with 4.4 and 2.5-fold reductions, respectively, in apoptosis compared with homotypic MCF7 cell cultures. Treatment of MCF7 cells cultured alone with high-energy mitochondrial "fuels" (L-lactate or ketone bodies) is sufficient to confer tamoxifen resistance, mimicking the effects of coculture with fibroblasts. To further demonstrate that epithelial cancer cell mitochondrial activity is the origin of tamoxifen resistance, we employed complementary pharmacological and genetic approaches. First, we studied the effects of two mitochondrial "poisons," namely metformin and arsenic trioxide (ATO), on fibroblast-induced tamoxifen resistance. We show here that treatment with metformin or ATO overcomes fibroblast-induced tamoxifen resistance in MCF7 cells. Treatment with the combination of tamoxifen plus metformin or ATO leads to increases in glucose uptake in MCF7 cells, reflecting metabolic uncoupling between epithelial cancer cells and fibroblasts. In coculture, tamoxifen induces the upregulation of TIGAR (TP53-induced glycolysis and apoptosis regulator), a p53 regulated gene that simultaneously inhibits glycolysis, autophagy and apoptosis and reduces ROS generation, thereby promoting oxidative mitochondrial metabolism. To genetically mimic the effects of coculture, we next recombinantly overexpressed TIGAR in MCF7 cells. Remarkably, TIGAR overexpression protects epithelial cancer cells from tamoxifen-induced apoptosis, providing genetic evidence that increased mitochondrial function confers tamoxifen resistance. Finally, CAFs also protect MCF7 cells against apoptosis induced by other anticancer agents, such as the topoisomerase inhibitor doxorubicin (adriamycin) and the PARP-1 inhibitor ABT-888. These results suggest that the tumor microenvironment may be a general mechanism for conferring drug resistance. In summary, we have discovered that mitochondrial activity in epithelial cancer cells drives tamoxifen resistance in breast cancer and that mitochondrial "poisons" are able to re-sensitize these cancer cells to tamoxifen. In this context, TIGAR may be a key "druggable" target for preventing drug resistance in cancer cells, as it protects cancer cells against the onset of stress-induced mitochondrial dys-function and aerobic glycolysis. PMID- 22041889 TI - Improvement of non-steroidal anti-inflammatory drug-induced gastrointestinal symptoms during proton pump inhibitor treatment: are G-protein beta3 subunit genotype, Helicobacter pylori status, and environmental factors response modifiers? AB - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with significant upper and lower gastrointestinal (GI) morbidity. AIM: To determine the efficacy and safety of pantoprazole versus placebo in controlling GI symptoms during treatment with NSAIDs and to evaluate the influence of potential response modifiers. METHODS: 800 patients with GI complaints during NSAID treatment were randomized to pantoprazole 20 mg once daily or placebo for 4 weeks in this double blind, multicenter trial. Assessments included the difference in cumulated overall symptom load of any GI complaint during treatment (primary endpoint), proportion of days without GI symptoms, and influence of risk factors such as gender, age, alcohol consumption, smoking, Helicobacter pylori status, and GNB3 genotype SNP rs5443 (825C>T) on symptom load. RESULTS: At 4 weeks, cumulated overall symptom load was significantly lower in pantoprazole than placebo recipients [p < 0.0001; intent-to-treat (ITT)]; the effect was statistically significant after 7 days' treatment. Pantoprazole versus placebo recipients had 54 versus 29% of days without GI symptoms (p < 0.0001; ITT). Neither common risk factors nor GNB3 genotype were significantly associated with therapeutic response, while GNB3 825TT versus CT was associated with a significantly higher baseline symptom load (p < 0.05). CONCLUSION: In the population studied, treatment with the proton pump inhibitor pantoprazole significantly improves GI symptoms during NSAID therapy, irrespective of the risk factors investigated or GNB3 genotype. PMID- 22041890 TI - SNX3 controls Wingless/Wnt secretion through regulating retromer-dependent recycling of Wntless. AB - Drosophila Wingless (Wg) acts as a morphogen during development. Wg secretion is controlled by a seven-pass transmembrane cargo Wntless (Wls). We have recently identified retromer as a key regulator involved in Wls trafficking. As sorting nexin (SNX) molecules are essential components of the retromer complex, we hypothesized that specific SNX(s) is required for retromer-mediated Wnt secretion. Here, we generated Drosophila mutants for all of the eight snx members, and identified Drosophila SNX3 (DSNX3) as an essential molecule required for Wg secretion. We show that Wg secretion and its signaling activity are defective in Dsnx3 mutant clones in wing discs. Wg levels in the culture medium of Dsnx3-depleted S2 cells are also markedly reduced. Importantly, Wls levels are strikingly reduced in Dsnx3 mutant cells, and overexpression of Wls can rescue the Wg secretion defect observed in Dsnx3 mutant cells. Moreover, DSNX3 can interact with the retromer component Vps35, and co-localize with Vps35 in early endosomes. These data indicate that DSNX3 regulates Wg secretion via retromer dependent Wls recycling. In contrast, we found that Wg secretion is not defective in cells mutant for Drosophila snx1 and snx6, two components of the classical retromer complex. Ectopic expression of DSNX1 or DSNX6 fails to rescue the Wg secretion defect in Dsnx3 mutant wing discs and in Dsnx3 dsRNA-treated S2 cells. These data demonstrate the specificity of the DSNX3-retromer complex in Wls recycling. Together, our findings suggest that DSNX3 acts as a cargo-specific component of retromer, which is required for endocytic recycling of Wls and Wg/Wnt secretion. PMID- 22041891 TI - Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. AB - Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of 'MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D(2), or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. PMID- 22041892 TI - Towards the role of metal ions in the structural variability of proteins: CdII speciation of a metal ion binding loop motif. AB - A de novo designed dodecapeptide (HS), inspired by the metal binding loops of metal-responsive transcriptional activators, was synthesized. The aim was to create a model system for structurally promiscuous and intrinsically unstructured proteins, and explore the effect of metal ions on their structure and dynamics. The interaction with Cd(II) was investigated by UV, synchrotron radiation CD, (1)H NMR, and perturbed angular correlation (PAC) of gamma-rays spectroscopy, pH potentiometry, and molecular modelling. The peptide mainly displays characteristics of random coil in the CD spectra, and the molecular dynamics simulations demonstrate that it is unstructured with transient and varying helical content. The spectroscopic studies revealed the formation of loop structures with the coordination of the two Cys-thiolates close to each end of the HS peptide, in the presence of one equivalent of Cd(II) per ligand. The imidazole moiety from histidine is also bound to Cd(II) at neutral pH and above. In the presence of 0.5 equivalent of Cd(II) per HS metal bridged structures with e.g. CdS(2)N(2) and possibly CdS(4) coordination geometries are formed above pH ~6. In an equilibrium of several co-existing species the peptide is exchanging between a number of structures also in its metal ion bound state(s), as indicated by NMR and PAC data. PMID- 22041894 TI - The role of the organic layer functionalization in the formation of silicon/organic layer/metal junctions with coinage metals. AB - The design of silicon/alkyl layer/metal junctions for the formation of optimal top metal contacts requires knowledge of the mechanistic and energetic aspects of the interactions of metal atoms with the modified surface. This involves (a) the interaction of the metal with the terminal groups of the organic layer, (b) the diffusion of metal atoms through the organic layer and (c) the reactions of metal atoms with the silicon surface atoms. The diffusion through the monolayer and the metal catalyzed breakage of Si-C bonds must be avoided to obtain high quality junctions. In this work, we performed a comprehensive density functional theory investigation to identify the reaction pathways of all these processes. In the absence of a reactive terminal group, gold atoms may penetrate through a compact alkyl monolayer on Si(111) with no energy barrier. However, the presence of thiol terminal groups introduces a high energy barrier which blocks the diffusion of metals into the monolayer. The diffusion barriers increase in the order Ag < Au < Cu and correlate with the stability of metal-thiolate complexes whereas the barriers for the formation of metal silicides increase in the order Cu < Au < Ag in correlation with the increasing metallic radii. The reactivity of gold clusters with functionalized Si(111) surfaces was also investigated. Metal silicide formation can only be avoided by a compact monolayer terminated by a reactive functional group. The mechanistic and energetic picture obtained in this work contributes to understanding of the factors that influence the quality of top metal contacts during the formation of silicon/organic layer/metal junctions. PMID- 22041895 TI - Salt sensitivity of minimal twin arginine translocases. AB - Bacterial twin arginine translocation (Tat) pathways have evolved to facilitate transport of folded proteins across membranes. Gram-negative bacteria contain a TatABC translocase composed of three subunits named TatA, TatB, and TatC. In contrast, the Tat translocases of most Gram-positive bacteria consist of only TatA and TatC subunits. In these minimal TatAC translocases, a bifunctional TatA subunit fulfils the roles of both TatA and TatB. Here we have probed the importance of conserved residues in the bifunctional TatAy subunit of Bacillus subtilis by site-specific mutagenesis. A set of engineered TatAy proteins with mutations in the cytoplasmic hinge and amphipathic helix regions were found to be inactive in protein translocation under standard growth conditions for B. subtilis or when heterologously expressed in Escherichia coli. Nevertheless, these mutated TatAy proteins did assemble into TatAy and TatAyCy complexes, and they facilitated membrane association of twin arginine precursor proteins in E. coli. Interestingly, most of the mutated TatAyCy translocases were salt-sensitive in B. subtilis. Similarly, the TatAC translocases of Bacillus cereus and Staphylococcus aureus were salt-sensitive when expressed in B. subtilis. Taken together, our present observations imply that salt-sensitive electrostatic interactions have critical roles in the preprotein translocation activity of certain TatAC type translocases from Gram-positive bacteria. PMID- 22041896 TI - Early contacts between substrate proteins and TatA translocase component in twin arginine translocation. AB - Twin-arginine translocation (Tat) is a unique protein transport pathway in bacteria, archaea, and plastids. It mediates the transmembrane transport of fully folded proteins, which harbor a consensus twin-arginine motif in their signal sequences. In Gram-negative bacteria and plant chloroplasts, three membrane proteins, named TatA, TatB, and TatC, are required to enable Tat translocation. Available data suggest that TatA assembles into oligomeric pore-like structures that might function as the protein conduit across the lipid bilayer. Using site specific photo-cross-linking, we have investigated the molecular environment of TatA under resting and translocating conditions. We find that monomeric TatA is an early interacting partner of functionally targeted Tat substrates. This interaction with TatA likely precedes translocation of Tat substrates and is influenced by the proton-motive force. It strictly depends on the presence of TatB and TatC, the latter of which is shown to make contacts with the transmembrane helix of TatA. PMID- 22041897 TI - Monosaccharide absorption activity of Arabidopsis roots depends on expression profiles of transporter genes under high salinity conditions. AB - Plant roots are able to absorb sugars from the rhizosphere but also release sugars and other metabolites that are critical for growth and environmental signaling. Reabsorption of released sugar molecules could help reduce the loss of photosynthetically fixed carbon through the roots. Although biochemical analyses have revealed monosaccharide uptake mechanisms in roots, the transporters that are involved in this process have not yet been fully characterized. In the present study we demonstrate that Arabidopsis STP1 and STP13 play important roles in roots during the absorption of monosaccharides from the rhizosphere. Among 14 STP transporter genes, we found that STP1 had the highest transcript level and that STP1 was a major contributor for monosaccharide uptake under normal conditions. In contrast, STP13 was found to be induced by abiotic stress, with low expression under normal conditions. We analyzed the role of STP13 in roots under high salinity conditions where membranes of the epidermal cells were damaged, and we detected an increase in the amount of STP13-dependent glucose uptake. Furthermore, the amount of glucose efflux from stp13 mutants was higher than that from wild type plants under high salinity conditions. These results indicate that STP13 can reabsorb the monosaccharides that are released by damaged cells under high salinity conditions. Overall, our data indicate that sugar uptake capacity in Arabidopsis roots changes in response to environmental stresses and that this activity is dependent on the expression pattern of sugar transporters. PMID- 22041898 TI - Nitric oxide modulates sodium vitamin C transporter 2 (SVCT-2) protein expression via protein kinase G (PKG) and nuclear factor-kappaB (NF-kappaB). AB - Ascorbate is an important antioxidant, which also displays important functions in neuronal tissues, including the retina. The retina is responsible for the initial steps of visual processing, which is further refined in cerebral high-order centers. The retina is also a prototypical model for studying physiologic aspects of cells that comprise the nervous system. Of major importance also is the cellular messenger nitric oxide (NO). Previous studies have demonstrated the significance of NO for both survival and proliferation of cultured embryonic retinal cells. Cultured retinal cells express a high-affinity ascorbate transporter, and the release of ascorbate is delicately regulated by ionotropic glutamate receptors. Therefore, we proposed whether there is interplay between the ascorbate transport system and NO signaling pathway in retinal cells. Here we show compelling evidence that ascorbate uptake is tightly controlled by NO and its downstream signaling pathway in culture. NO also modulates the expression of SVCT-2, an effect mediated by cGMP and PKG. Kinetic studies suggest that NO increases the transport capacity for ascorbate, but not the affinity of SVCT-2 for its substrate. Interestingly, NO utilizes the NF-kappaB pathway, in a PKG dependent manner, to modulate both SVCT-2 expression and ascorbate uptake. These results demonstrate that NO exerts a fine-tuned control of the availability of ascorbate to cultured retinal cells and strongly reinforces ascorbate as an important bioactive molecule in neuronal tissues. PMID- 22041899 TI - Dual specificity of anti-CXCL10-CXCL9 antibodies is governed by structural mimicry. AB - Dual-specific antibodies are characterized by an antigen-combining site mediating specific interactions with two different antigens. We have generated five dual specific single chain variable fragments (scFv) that neutralize the activity of the two chemokines, CXCL9 and CXCL10, to bind to their receptor CXCR3. To better understand how these dual-specific scFvs bind these two chemokines that only share a 37% sequence identity, we mapped their epitopes on human CXCL9 and CXCL10 and identified serine 13 (Ser(13)) as a critical residue. It is conserved between the two chemokines but not in the third ligand for CXCR3, CXCL11. Furthermore, Ser(13) is exposed in the tetrameric structure of CXCL10, which is consistent with our finding that the scFvs are able to bind to CXCL9 and CXCL10 immobilized on glycosaminoglycans. Overall, the data indicate that these dual-specific scFvs bind to a conserved surface involved in CXCR3 receptor interaction for CXCL10 and CXCL9. Thus, structural mimicry between the two targets is likely to be responsible for the observed dual specificity of these antibody fragments. PMID- 22041900 TI - Phospholipase Cgamma2 (PLCgamma2) is key component in Dectin-2 signaling pathway, mediating anti-fungal innate immune responses. AB - C-type lectin receptors (CLRs) such as Dectin-2 function as pattern recognition receptors to sense fungal infection. However, the signaling pathways induced by these receptors remain largely unknown. Previous studies suggest that the CLR induced signaling pathway may utilize similar signaling components as the B cell receptor-induced signaling pathway. Phospholipase Cgamma2 (PLCgamma2) is a key component in B cell receptor signaling, but its role in other signaling pathways has not been fully characterized. Here, we show that PLCgamma2 functions downstream of Dectin-2 in response to the stimulation by the hyphal form of Candida albicans, an opportunistic pathogenic fungus. Using PLCgamma2- and PLCgamma1-deficient macrophages, we found that the lack of PLCgamma2, but not PLCgamma1, impairs cytokine production in response to infection with C. albicans. PLCgamma2 deficiency results in the defective activation of NF-kappaB and MAPK and a significantly reduced production of reactive oxygen species following fungal challenge. In addition, PLCgamma2-deficient mice are defective in clearing C. albicans infection in vivo. Together, these findings demonstrate that PLCgamma2 plays a critical role in CLR-induced signaling pathways, governing antifungal innate immune responses. PMID- 22041902 TI - Caenorhabditis elegans Delta12-desaturase FAT-2 is a bifunctional desaturase able to desaturate a diverse range of fatty acid substrates at the Delta12 and Delta15 positions. AB - Caenorhabditis elegans FAT-2 has been characterized as fatty acid Delta12 desaturase able to desaturate C16 and C18 fatty acids. However, in this report we show that when expressed in yeast cells this enzyme can also catalyze Delta15 desaturation. This results in the production of both linoleic acid (omega6 C18:2Delta9,12) and linolenic acid (omega3 C18:3Delta9,12,15) from oleic acid (C18:1Delta9) substrate, and hexadecadienoic acid (omega4 C16:2Delta9,12) and hexadecatrienoic acid (omega1 C16:3Delta9,12,15) from palmitoleic acid (C16:1Delta9) substrate. In addition, this enzyme can also produce C14:2Delta9,12, C15:2Delta9,12, C17:2Delta9,12, and C18:4Delta6,9,12,15 when C14:1Delta9, C15:1Delta9, C17:1Delta9, and C18:3Delta6,9,12 substrates are available in yeast cells. Mass spectrometry analysis of 2,4-dimethyloxazoline modification of fatty acid methyl esters confirms the positions of all newly formed double bonds. These results indicate that when expressed in yeast the C. elegans Delta12-desaturase CeFAT-2 shows a characteristic of a bifunctional Delta12/Delta15-desaturase and has a great deal of elasticity with respect to fatty acid chain length in being able to accept fatty acids ranging from C14 to C18. Interestingly, despite possessing a bifunctional Delta12/Delta15 desaturation activity, phylogenetic analysis suggests that C. elegans Delta12 desaturase CeFAT-2 might have arisen independently from other reported dual Delta12/Delta15-desaturases from fungi and protozoa. PMID- 22041901 TI - Type II arginine methyltransferase PRMT5 regulates gene expression of inhibitors of differentiation/DNA binding Id2 and Id4 during glial cell differentiation. AB - PRMT5 is a type II protein arginine methyltranferase that catalyzes monomethylation and symmetric dimethylation of arginine residues. PRMT5 is functionally involved in a variety of biological processes including embryo development and circadian clock regulation. However, the role of PRMT5 in oligodendrocyte differentiation and central nervous system myelination is unknown. Here we show that PRMT5 expression gradually increases throughout postnatal brain development, coinciding with the period of active myelination. PRMT5 expression was observed in neurons, astrocytes, and oligodendrocytes. siRNA mediated depletion of PRMT5 in mouse primary oligodendrocyte progenitor cells abrogated oligodendrocyte differentiation. In addition, the PRMT5-depleted oligodendrocyte progenitor and C6 glioma cells expressed high levels of the inhibitors of differentiation/DNA binding, Id2 and Id4, known repressors of glial cell differentiation. We observed that CpG-rich islands within the Id2 and Id4 genes were bound by PRMT5 and were hypomethylated in PRMT5-deficient cells, suggesting that PRMT5 plays a role in gene silencing during glial cell differentiation. Our findings define a role of PRMT5 in glial cell differentiation and link PRMT5 to epigenetic changes during oligodendrocyte differentiation. PMID- 22041903 TI - Survival impact of adjuvant paclitaxel and carboplatin for early-stage ovarian clear-cell carcinoma with complete surgical staging. AB - OBJECTIVES: The aim of this study was to estimate the survival impact of adjuvant paclitaxel and carboplatin (TC) compared to cisplatin (CDDP)-based chemotherapies for early-stage ovarian clear-cell carcinoma (CCC). METHODS: Clinicopathologic information on 99 stage I-II CCC patients was obtained between 1987 and 2005. All patients underwent complete surgical staging including systemic lymphadenectomy, followed by TC or various CDDP-based regimens. In the present study, only CCC patients with no residual tumor were enrolled. RESULTS: The median age was 53 years and ranged from 30 to 69 years. Fifty-three (53.5%) patients received TC and 46 (46.5%) patients underwent various CDDP-based chemotherapies after initial surgery. Five-year progression-free survival (PFS) rates of TC and various CDDP groups were 66.5 and 75.8%, respectively (n.s., p = 0.933). In addition, 5-year overall survival (OS) rates of TC and various CDDP groups were 82.4 and 82.3%, respectively (n.s., p = 0.583). In multivariate analyses of OS and PFS, the regimen of chemotherapywas not a significant prognostic factor (OS, p = 0.502; PFS, p = 0.977. CONCLUSIONS: In our current examination of the long-term survival of early-stage CCC patients, we did not identify a superiority of TC over various CDDP-based regimens as frontline adjuvant chemotherapy. PMID- 22041904 TI - Enhancement of affinity in molecular recognition via hydrogen bonds by POSS-core dendrimer and its application for selective complex formation between guanosine triphosphate and 1,8-naphthyridine derivatives. AB - We report that a polyhedral oligomeric silsesquioxane (POSS) core in a dendrimer can enhance the affinity of the molecular recognition via hydrogen bonds between 1,8-naphthyridine and guanosine nucleotides. The complexation of the naphthyridine ligands with a series of guanosine nucleotides was investigated, and it is shown that the POSS core should play a significant role in the stabilization of the complexes via hydrogen bonds. Finally, we demonstrate that the 1,8-naphthyridine ligand can selectively recognize guanosine triphosphate by assisting with the POSS-core dendrimer. PMID- 22041905 TI - Highly shape-selective guest encapsulation in the precisely defined cavity of a calix[4]arene-capped metalloporphyrin. AB - We developed a metalloporphyrin-based molecular container capped with a calix[4]arene, and its rigid cavity distinguished the slight structural differences in the aromatic guests. PMID- 22041906 TI - A case series of individuals with analytically confirmed acute diphenyl-2 pyrrolidinemethanol (D2PM) toxicity. AB - PURPOSE: There is increasing interest in the use of pipradrol and pipradrol derivatives, such as diphenylproplinol [diphenyl-2-pyrrolidinemethanol (D2PM)] and desoxypipradrol [2-diphenylmethylpiperidine (2-DPMP)], as recreational drugs. There is limited information on the acute toxicity related to both D2PM and 2 DPMP. We report here a case series of five individuals with acute toxicity related to the use of D2PM. CASE SERIES: Five patients aged between 21 and 33 years old presented to the Emergency Department (ED) on unrelated occasions having used a range of different novel psychoactive substances; none had actually purchased D2PM. They presented with ongoing prolonged neuropsychiatric symptoms of agitation, anxiety and insomnia lasting 24-96 h post-ingestion. None had evidence of sympathomimetic toxicity on presentation to the ED. All were reassured and discharged home after review. TOXICOLOGICAL SCREENING: Urine collection at the time of presentation to the ED was subsequently analysed by gas chromatography-mass spectrometry (GC-MS). All of the urine samples tested positive for D2PM and benzophenone. Additional screening by liquid chromatography tandem mass-spectrometry (LC-MS-MS) demonstrated that the benzophenone detected was an analytical artefact due to the high-injection temperature of the GC-MS analysis. CONCLUSIONS: This descriptive case series provides more detailed information on the acute toxicity related to the use of D2PM. This information is useful for clinical pharmacologists and clinicians managing these individuals to be able to provide more appropriate advice on the acute toxicity associated with the use of D2PM, particularly in relation to the prolonged neuropsychiatric symptoms seen. PMID- 22041907 TI - Continuous in situ generation and reaction of phosgene in a microflow system. AB - Continuous in situ generation of phosgene and its use in acid chloride formation in a microflow system were demonstrated. The acid chloride was subsequently coupled with an amine in high yield without severe epimerization. PMID- 22041908 TI - Flow behavior of digesta and the absorption of nutrients in the gastrointestine. AB - Digesta flow-behavior types in the intestinal lumen, such as turbulent and laminar flow, should define modes of digestion and absorption. This review presents a simulation of flow behavior in the intestinal lumen and discusses the behavior of nutrients and enzymes in the intestinal lumen under laminar-flow conditions. The significance of digesta viscosity for glucose and water absorption and digestion and fermentation in the intestine is also discussed. PMID- 22041909 TI - Vitamin K1 (phylloquinone) or vitamin K2 (menaquinone-4) induces intestinal alkaline phosphatase gene expression. AB - Alkaline phosphatase (ALP) hydrolyzes a variety of monophosphate esters into inorganic acid and alcohol at a high optimum pH (pH 8-10). Previously, we identified a significant increase of intestinal ALP (IAP) activity in the rat intestine on long-term dietary vitamin K supplementation. However, it was unclear whether the induction of ALP gene expression was caused by vitamin K intake. In the present study, we examined the effects of vitamin K on IAP gene expression. A total of 21 male ICR strain mice (7 wk old) were divided into three groups: control, PK, and MK groups. Mice were orally administered a 0.1-mL solution of physiological saline in the control group, phylloquinone (3 mg/kg mouse) in the PK group, and menaquinone-4 (3 mg/kg mouse) in the MK group. Four hours after administration, we determined the ALP activity of the intestinal mucosa in three areas (duodenum, jejunum, and ileum). In the MK groups, the levels of ALP activity in the jejunum increased significantly compared with the control. Moreover, reverse transcription-polymerase chain reaction (RT-PCR) analysis using specific primers revealed that IAP mRNA expression was significantly enhanced in the jejunum in both PK and MK groups. Interestingly, vitamin K administration also increased the expression of pregnane X receptor mRNA. This is the first report concerning IAP mRNA expression induced by oral administration of vitamin K. The results support the possible involvement of vitamin K in the regulation of IAP mRNA expression as a novel pharmacological effect of vitamin K. PMID- 22041910 TI - High dose of pyridoxine induces IGFBP-3 mRNA expression in MCF-7 cells and its induction is inhibited by the p53-specific inhibitor pifithrin-alpha. AB - It has been reported that supplementation with high-dose vitamin B(6) (B(6)) exerts antitumor effects in rodent models of cancer. However, the mechanism of these effects remains poorly understood. High-dose B(6) also suppresses cell proliferation and induces apoptosis of human breast adenocarcinoma MCF-7 cells. Based on preliminary experiments using DNA microarray analyses, we hypothesized that high-dose pyridoxine (PN) might induce IGF-binding protein-3 (IGFBP-3) expression in MCF-7 cells. In this study, we investigated IGFBP-3 induction by 3 or 10 mM PN using a quantitative real-time PCR method. We found that the induction reached a maximum of 24-fold with 10 mM PN for 72 h compared with non treated cells. The induction of IGFBP-3 by PN was inhibited by a p53-specific inhibitor, pifithrin-alpha, in a dose-dependent manner, but was not affected by PD169316 (MAPK inhibitor), AS601245 (c-Jun N-terminal kinase inhibitor) or SL327 (MEK1/2 inhibitor). High-dose PN did not induce p53 mRNA expression. The IGFBP-3 induction by PN seemed to be related to p53 activation. PMID- 22041911 TI - Effect of dietary gamma-aminobutyric acid on the brain protein synthesis rate in hypophysectomized aged rats. AB - The purpose of this study was to determine whether the regulation of brain protein synthesis was mediated through changes in the plasma concentration of growth hormone (GH) when dietary gamma-aminobutyric acid (GABA) treatment was manipulated in hypophysectomized or sham-operated aged rats. Experiments were done on four groups of hypophysectomized and sham-operated (24-wk-old) male rats given 0% or 0.5% GABA added to a 20% casein diet. The concentrations of plasma GH and fractional rates of protein synthesis in the brains increased significantly with the 20% casein+0.5% GABA compared with the 20% casein diet alone in the sham operated rats. However GABA treatment to the basal diet did not affect the rates of protein synthesis in the hypophysectomized rats. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA.d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was also related to the fractional rate of protein synthesis in these organs. The results suggest that treatment with GABA is likely to increase the concentrations of GH and the rate of brain protein synthesis in sham operated rats only, not in hypophysectomized rats, and that the GABA-induced increase in the concentration of GH may be primarily responsible for changes in the brain protein synthesis. The RNA activity is at least partly related to the fractional rate of brain protein synthesis. PMID- 22041912 TI - Acidic xylooligosaccharide preserves hepatic iron storage level in adult female rats fed a low-iron diet. AB - Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. This experiment was conducted to investigate whether acidic xylooligosaccharide (U-XOS), expected to have a high iron bioavailability, was useful in the prevention of iron deficiency. Experiment 1: Nineteen female Sprague-Dawley rats (20 wk old) were fed three different diets for 28 d; a U-XOS-supplemented low iron diet (LI-X, n=7), a low-iron diet (LI, n=6), and a control diet (C, n=6). On day 28, the LI-X and LI groups showed iron deficiency without anemia. A significant difference in the total and unsaturated iron binding capacity, and serum transferrin saturation level was shown in the LI-X and LI groups, compared with the C group. However, the decrease of hepatic iron content of the LI-X group was suppressed compared with the LI group. Experiment 2: Eleven male Sprague Dawley rats (7 wk old) were fed a U-XOS-supplemented diet (X, n=5) or a control diet (C, n=6) for 7 d. No significant difference in body weight gain or food intake was demonstrated between the two groups; the apparent iron absorption rate of the X group increased clearly compared with that of the C group. These results suggested that a U-XOS diet could preserve storage of hepatic iron in adult female rats fed a low-iron diet and could prevent IDA by promotion of dietary iron absorption, inhibition of iron excretion, and/or improvement of iron bioavailability. PMID- 22041913 TI - Mammalian selenocysteine lyase is involved in selenoprotein biosynthesis. AB - Selenocysteine lyase (SCL) catalyzes the decomposition of L-selenocysteine to yield L-alanine and selenium by acting exclusively on l-selenocysteine. The X-ray structural analysis of rat SCL has demonstrated how SCL discriminates L selenocysteine from L-cysteine on the molecular basis. SCL has been proposed to function in the recycling of the micronutrient selenium from degraded selenoproteins containing selenocysteine residues, but the role of SCL in selenium metabolism in vivo remains unclear. We here demonstrate that the (75)Se labeling efficiency of selenoproteins with (75)Se-labeled selenoprotein P (Sepp1) as a selenium source was decreased in HeLa cells transfected with SCL siRNA as compared to the cells transfected with control siRNA. Immunocytochemical analyses showed high SCL expression in kidney and liver cells, where selenocysteine is recovered from selenoproteins. Mature testes of mice exhibited a specific staining pattern of SCL in spermatids that actively produce selenoproteins. However, SCL was weakly expressed in Sertoli cells, which receive Sepp1 and supply selenium to germ cells. These demonstrate that SCL occurs in the cells requiring selenoproteins, probably to recycle selenium derived from selenoproteins such as Sepp1. PMID- 22041914 TI - Protective effect of red-stemmed type of Ipomoea aquatica Forsk against CCl4 induced oxidative damage in mice. AB - Water spinach (Ipomoea aquatica Forsk; I. aquatica) of the green-stemmed type (green type) is widely consumed, but there also exists a red-stemmed variety (red type). In the present study, the antioxidant capacity of the red type was compared to that of the green type in carbon tetrachloride (CCl(4))-treated mice. CCl(4)-induced thiobarbituric acid reactive substrate (TBARS) formation in the liver was significantly suppressed in mice fed 5% red-type I. aquatica, while the green type showed no effect. Hydrophobic oxygen radical absorbance capacity (H ORAC(FL)) in the red type showed a lower level than that in the green type; however, lipophilic ORAC (L-ORAC(FL)) and total-ORAC(FL) levels were significantly higher in the red type than in the green type. alpha-Tocopherol, anthocyanidin/proanthocyanidin, and beta-carotene contents were all significantly higher in the red type than in the green type. These results suggest that the wild red-type I. aquatica contains certain lipophilic components that exert antioxidant capacities not only in vitro but also in vivo. Such effective components in the red type would be beneficial phytochemicals for suppressing several diseases related to oxidative stress. PMID- 22041915 TI - Tube-enteral feeding for frail elderly patients with oropharyngeal dysphagia--not only yes or no, but when? PMID- 22041916 TI - IUNS Workshop on Capacity and Leadership Development in Nutritional Sciences held in Tokyo 2010. PMID- 22041917 TI - Chronic herpes zoster duplex bilateralis. AB - Although varicella zoster virus latency has been demonstrated in several sensory ganglia, herpes zoster usually effects only one single, either left or right, dermatome in half of the body. In immunocompromised patients, more than one contiguous unilateral dermatome may be involved. Bilateral non-contiguous herpes zoster, also termed herpes zoster duplex, is rarely reported. Chronic varicella zoster virus skin infection is another rare entity encountered in HIV-infected and immunocompromised patients, often associated with aciclovir resistance. We describe here a patient with chronic lymphocytic leukaemia, who presented simultaneously non-contiguous bilateral and chronic herpes zoster lasting for more than 2 months, with resistance to aciclovir. To our knowledge, this is the first report of chronic herpes zoster duplex bilateralis. Physicians should be aware of and recognize these atypical manifestations of varicella zoster virus. PMID- 22041918 TI - Combination of angiotensin II receptor blockers promotes proton pump inhibitor based healing of reflux esophagitis. AB - BACKGROUND: Several studies have described factors associated with the failure of proton pump inhibitors (PPIs) to effect endoscopic healing of reflux esophagitis (RE), but few studies have addressed factors promoting PPI-based endoscopic healing. We performed post hoc analysis of a multicenter prospective cohort of RE patients to identify factors encouraging endoscopic healing of this disorder. METHODS: Patients with RE received 10 or 20 mg rabeprazole for 8 weeks, and endoscopic findings before and after treatment were studied. To evaluate the effects of patient background factors on endoscopic healing, we performed multiple logistic regression analysis and determined the respective odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 454 patients who underwent endoscopy at baseline and again at week 8 were included in the analysis. After 8 weeks of treatment, improvement in endoscopic findings was observed in 94.1% (427/454) of patients, and endoscopic healing was seen in 76.7% (348/454). Multiple logistic regression analysis revealed that a combination of angiotensin II receptor blockers (ARBs) had a significant positive impact on endoscopic healing (OR 3.9, 95% CI 1.411-10.903), but no significant positive relationship was seen for other concomitant drugs such as nonsteroidal anti inflammatory drugs and calcium channel blockers. Severe RE at baseline (OR 0.365, 95% CI 0.281-0.475) and PPI therapy prior to enrollment (OR 0.154, 95% CI 0.052 0.453) were found to have significant negative effects on endoscopic healing. CONCLUSIONS: Concomitant use of ARBs may promote endoscopic healing of RE treated with PPIs. PMID- 22041920 TI - Glycogen synthase kinase 3beta inhibition sensitizes pancreatic cancer cells to gemcitabine. AB - BACKGROUND: Pancreatic cancer is obstinate and resistant to gemcitabine, a standard chemotherapeutic agent for the disease. We previously showed a therapeutic effect of glycogen synthase kinase-3beta (GSK3beta) inhibition against gastrointestinal cancer and glioblastoma. Here, we investigated the effect of GSK3beta inhibition on pancreatic cancer cell sensitivity to gemcitabine and the underlying molecular mechanism. METHODS: Expression, phosphorylation, and activity of GSK3beta in pancreatic cancer cells (PANC-1) were examined by Western immunoblotting and in vitro kinase assay. The combined effect of gemcitabine and a GSK3beta inhibitor (AR-A014418) against PANC-1 cells was examined by isobologram and PANC-1 xenografts in mice. Changes in gene expression in PANC-1 cells following GSK3beta inhibition were studied by cDNA microarray and reverse transcription (RT)-PCR. RESULTS: PANC-1 cells showed increased GSK3beta expression, phosphorylation at tyrosine 216 (active form), and activity compared with non-neoplastic HEK293 cells. Administration of AR-A014418 at pharmacological doses attenuated proliferation of PANC-1 cells and xenografts, and significantly sensitized them to gemcitabine. Isobologram analysis determined that the combined effect was synergistic. DNA microarray analysis detected GSK3beta inhibition-associated changes in gene expression in gemcitabine-treated PANC-1 cells. Among these changes, RT-PCR and Western blotting showed that expression of tumor protein 53-induced nuclear protein 1, a gene regulating cell death and DNA repair, was increased by gemcitabine treatment and substantially decreased by GSK3beta inhibition. CONCLUSIONS: The results indicate that GSK3beta inhibition sensitizes pancreatic cancer cells to gemcitabine with altered expression of genes involved in DNA repair. This study provides insight into the molecular mechanism of gemcitabine resistance and thus a new strategy for pancreatic cancer chemotherapy. PMID- 22041919 TI - Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression. AB - BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes. METHODS: Surgically resected IPMNs (n = 25) were classified into four subtypes by hematoxylin and eosin (H&E) and mucin immunostaining. Mutations in KRAS, BRAF, and PIK3CA genes and expression of CDKN2A, TP53, SMAD4, phospho-ERK, and phospho SMAD1/5/8 proteins were examined. RESULTS: There were 11 gastric, 11 intestinal, one pancreatobiliary, and two oncocytic types in this study. We then compared the two major subtypes, gastric-type and intestinal-type IPMN. Gastric-type IPMN showed a significantly higher incidence of KRAS mutations (9/11, 81.8%) compared with intestinal type (3/11, 27.3%; p < 0.05), although the intestinal type showed a higher grade of dysplasia than gastric type (p < 0.01). All cases with KRAS mutations showed phospho-ERK immunostaining. In contrast, intestinal type (9/11, 81.8%) showed more frequent SMAD1/5/8 phosphorylation compared with gastric-type IPMN (3/11, 27.3%; p < 0.05%). CONCLUSIONS: There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN. In particular, KRAS mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreatic cancer in IPMN patients. PMID- 22041921 TI - Diagnosis of gastroenterological diseases by metabolome analysis using gas chromatography-mass spectrometry. AB - Recently, metabolome analysis has been increasingly applied to biomarker detection and disease diagnosis in medical studies. Metabolome analysis is a strategy for studying the characteristics and interactions of low molecular weight metabolites under a specific set of conditions and is performed using mass spectrometry and nuclear magnetic resonance spectroscopy. There is a strong possibility that changes in metabolite levels reflect the functional status of a cell because alterations in their levels occur downstream of DNA, RNA, and protein. Therefore, the metabolite profile of a cell is more likely to represent the current status of a cell than DNA, RNA, or protein. Thus, owing to the rapid development of mass spectrometry analytical techniques metabolome analysis is becoming an important experimental method in life sciences including the medical field. Here, we describe metabolome analysis using liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry (GC-MS), capillary electrophoresis-mass spectrometry, and matrix assisted laser desorption ionization-mass spectrometry. Then, the findings of studies about GC-MS-based metabolome analysis of gastroenterological diseases are summarized, and our research results are also introduced. Finally, we discuss the realization of disease diagnosis by metabolome analysis. The development of metabolome analysis using mass spectrometry will aid the discovery of novel biomarkers, hopefully leading to the early detection of various diseases. PMID- 22041922 TI - Patterns of care studies in oncology: considerable potential utility, but risk of serious bias. PMID- 22041923 TI - Prevalence of lower urinary tract symptoms in Austrian males: update 2009. AB - INTRODUCTION: The prevalence of lower urinary tract symptoms (LUTS) in a representative sample of Austrian males aged 15-89 years was assessed in 2009. The results were compared with the findings of a similar study conducted in 1995. MATERIALS AND METHODS: A population-based cross-sectional survey on LUTS was conducted in 2009 in Austria. A quota sample of 1,926 Austrians was selected. The sample comprised 0.03% of the population and was representative in terms of age, sex, occupational status and area of residence. RESULTS: Some degree of LUTS is reported by 64.6% of the male population in Austria aged 15-89 years. IPSS correlates significantly with age. In all age groups storage symptoms are more prevalent than voiding symptoms. The prevalence of voiding symptoms (IPSS >0) among Austrian males is 35.5% and the prevalence of storage symptoms is 61.6%. In both groups the prevalence increases with age. Compared to 1995, the prevalence of dissatisfaction declined significantly. An extrapolated number of more than 35,000 men are 'terribly' dissatisfied with their current urinary condition. CONCLUSIONS: The prevalence of LUTS in Austria meliorated in Austria significantly between 1995 and 2009. This in part may be attributed to intensified contact of males with urologists in the past. PMID- 22041924 TI - Capsule-endoscopic findings of ulcerative colitis patients. AB - BACKGROUND/AIMS: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by diffuse mucosal inflammation, traditionally regarded as being limited to the colorectum. Although several gastroduodenal lesions have also been reported recently in cases of UC, in general, small-bowel lesions in UC are believed to be extremely rare. The aim of this study was to examine the small bowel by capsule endoscopy in patients with UC. METHODS: The study was conducted in 23 well-documented UC patients and 23 control volunteers. The frequency of small-bowel lesions, the number of small-bowel lesions per patient and the capsule endoscopy score were comparatively evaluated between the two groups. RESULTS: Of the 23 UC patients, 13 (57%) showed small-bowel lesions, and 8 (35%) had erosions. There were significant differences in the frequency of the small bowel lesions (p < 0.001) and erosions (p = 0.009) between the two groups. The capsule endoscopy score was correlated with the UC disease activity index (r = 0.718, p < 0.001). CONCLUSIONS: This is the first capsule-endoscopic study conducted to examine the small-bowel involvement in UC patients as compared with the healthy volunteers. It was concluded that UC, a chronic inflammatory bowel disease, can also involve the small bowel. PMID- 22041925 TI - CD1d-independent activation of mouse and human iNKT cells by bacterial superantigens. AB - Invariant NKT (iNKT) cells are infrequent but important immunomodulatory lymphocytes that exhibit CD1d-restricted reactivity with glycolipid Ags. iNKT cells express a unique T-cell receptor (TCR) composed of an invariant alpha chain, paired with a limited range of beta-chains. Superantigens (SAgs) are microbial toxins defined by their ability to activate conventional T cells in a TCR beta-chain variable domain (Vbeta)-specific manner. However, whether iNKT cells are directly activated by bacterial SAgs remains an open question. Herein, we explored the responsiveness of mouse and human iNKT cells to a panel of staphylococcal and streptococcal SAgs and examined the contribution of major histocompatibility complex (MHC) class II and CD1d to these responses. Bacterial SAgs that target mouse Vbeta8, such as staphylococcal enterotoxin B (SEB), were able to activate mouse hybridoma and primary hepatic iNKT cells in the presence of mouse APCs expressing human leukocyte antigen (HLA)-DR4. iNKT cell-mediated cytokine secretion in SEB-challenged HLA-DR4-transgenic mice was CD1d-independent and accompanied by a high interferon-gamma:interleukin-4 ratio consistent with an in vivo Th1 bias. Furthermore, iNKT cells from SEB-injected HLA-DR4-transgenic mice, and iNKT cells from SEB-treated human PBMCs, showed early activation by intracellular cytokine staining and CD69 expression. Unlike iNKT cell stimulation by alpha-galactosylceramide, stimulation by SEB did not induce TCR downregulation of either mouse or human iNKT cells. We conclude that Vbeta8-targeting bacterial SAgs can activate iNKT cells by utilizing a novel pathway that requires MHC class II interactions, but not CD1d. Therefore, iNKT cells fulfill important effector functions in response to bacterial SAgs and may provide attractive targets in the management of SAg-induced illnesses. PMID- 22041926 TI - Non-surgical approach to small cell carcinoma of the esophagus: does this rare disease have the same tumor behavior as SCLC? AB - BACKGROUND: We conducted a retrospective analysis to clarify the clinical profile of a nonsurgical approach to small cell carcinoma of the esophagus (SCEC). PATIENTS AND METHODS: SCEC patients in our database were reviewed. Consistent with the standard approach to small cell carcinoma of the lung (SCLC), chemoradiotherapy was the first choice for limited disease (LD)-SCEC in our institution while chemotherapy was the first choice for extensive disease (ED) SCEC. Our strategy did not include prophylactic cranial irradiation. RESULTS: Eighteen patients were treated between January 1996 and December 2006, of whom 10 had LD-SCEC and 8 had ED-SCEC. Regarding response to chemoradiotherapy in patients with LD-SCEC, CR rate at the primary site was 90% (9/10) and total CR rate was 80% (8/10). With a median follow-up period of 55.3 months, median survival time in LD-SCEC and ED-SCEC patients was 17.3 and 13.9 months, respectively, showing no significant difference (p = 0.57). Brain metastases occurred in only one patient. On follow-up, eight patients with LD-SCEC and seven with ED-SCEC died of disease. Only 2 patients died of local progression, while the remaining 13 died of disease progression of distant metastases. CONCLUSION: Despite providing good local control, chemoradiotherapy appeared to have insufficient potential to cure LD-SCEC. Prophylactic brain irradiation for SCEC is unnecessary. PMID- 22041927 TI - The prognostic analysis of clinical breast cancer subtypes among patients with liver metastases from breast cancer. AB - BACKGROUND: To determine whether the inferior outcome noted with triple-negative breast cancer (TNBC) reflects a higher risk population among patients with breast cancer liver metastases. METHODS: A total of 123 patients with breast cancer liver metastases diagnosed at Tianjin Medical University Cancer Hospital were included in this study. Breast cancer subtype was assigned using immunohistochemistry or fluorescence in situ hybridization: hormone receptor (HR) positive (+)/human epidermal growth factor receptor 2 (HER2) negative (-), HR+/HER2+, HR-/HER2+ and triple-negative subtype. Clinical features and survival were evaluated in different subtypes. RESULTS: The median age at breast cancer diagnosis was 47 years (range, 23-67 years). Breast cancer subtype was confirmed in all patients (39.8% with HR+/HER2-, 24.4% with HR+/HER2+, 15.3% with HR-/HER2+ and 20.3% with TNBC). The median overall survival after liver metastases was 29 months (range, 4-89 months), and the overall 1-, 2- and 3-year survival rate was 68.3, 48.0 and 34.1%, respectively. Survival was found to be impacted by breast cancer subtype (P = 0.001), and was shortest for patients with TNBC. Time to liver metastases (TTLM) less than 24 months and liver metastasis lesions >=3 were found to be important predictors of poor survival after liver metastases (P = 0.009 and 0.001, respectively). CONCLUSIONS: The results indicate that clinical breast cancer subtype remains an independent prognostic predictor among patients with breast cancer liver metastases. Liver metastases arising from TNBC confers the worst prognosis, and novel agents capable of controlling intrahepatic and extrahepatic TNBC are needed. PMID- 22041928 TI - Caffeine-potentiated chemotherapy for clear cell sarcoma: a report of five cases. AB - BACKGROUND: Clear cell sarcoma is a rare malignant tumor of soft tissue which is most commonly encountered in the extremities, especially in the foot and ankle. This tumor is slow-growing and looks like a benign tumor; it is therefore often treated inadequately and its high rate of recurrence and metastases results in a poor prognosis. Caffeine has been used as a chemotherapy potentiator that inhibits DNA damage repair and enhances the cytocidal effects of anti-cancer drugs. This study reports the effect of caffeine-potentiated chemotherapy for clear cell sarcoma in five patients. METHODS: Caffeine-potentiated chemotherapy was administered to five patients with clear cell sarcoma. Three to five courses of intra-arterial chemotherapy using cisplatin, doxorubicin and caffeine were administered preoperatively, at 3-week intervals. Conservatively, wide margin surgery was performed following the preoperative chemotherapy. Intravenous cisplatin and doxorubicin with caffeine were administered three to six times to the patients who responded to the preoperative chemotherapy. This study evaluated the response to chemotherapy, recurrence, metastasis and the overall prognosis in these five patients. RESULTS: Four of the eligible patients responded to preoperative chemotherapy. Local recurrence occurred in only one of the five patients. Distant metastasis newly developed in one patient. All five patients survive. CONCLUSION: Caffeine-potentiated chemotherapy can be effective treatment for clear cell sarcoma not only as initial therapy, but also as salvage therapy. PMID- 22041929 TI - A case of intimal sarcoma of the pulmonary artery successfully treated with chemotherapy. AB - Intimal sarcoma of pulmonary artery (PAIS) is a rare disease with no characteristic symptoms. No standard therapeutic guidelines have been established so far. A 55-year-old woman who underwent pulmonary endarterectomy in 2005 with a pathological and immunohistochemical result of PAIS was re-admitted to our hospital on August 24, 2009, presenting with cough and dyspnea. The thoracic computed tomography (CT) scan revealed a 12.5 cm * 9 cm well-defined mass in the right lobe, considered a local neoplasm recurrence after a 44 month symptom-free period. As surgical resection was not proposed, she received combined chemotherapy consisting of doxorubicin, cisplatin, and ifosfamide for two cycles. Because of intolerable side effects, she received vinorelbine and cisplatin for the next four cycles. CT scans after six cycles showed remarkable regression of the tumor. After that, she began to take oral cyclophosphamide (50 mg t.i.d) everyday as a maintenance therapy. As of the time of writing, 19 months after the onset of the recurrence, she remains stable. Several antineoplastic drugs have been reported to be used in PAIS, with poor effects in most cases. To our knowledge, this is the first case of PAIS that has been successfully treated by a vinorelbine-based regimen used as second-line chemotherapy. Vinorelbine is a promising drug that may be relatively well tolerated in heavily pretreated patients with PAIS. PMID- 22041932 TI - Vaginal cleansing practices in HIV infected Zambian women. AB - Vaginal practices are a variety of behavioral techniques that women use to manage their sexual life and personal hygiene. Women perceive vaginal practices as a beneficial practice. However, vaginal cleansing has been identified as one of the main risk factors for bacterial vaginosis and is potentially implicated in Human Immune Deficiency Virus (HIV) and sexually transmitted infection transmission. This study examined the prevalence of vaginal practices and the types of practices used among a sample of HIV positive women living in Lusaka, Zambia. Over 90% of all women recruited engaged in vaginal practices. Certain practices, such as use of water or soap, were more frequently used for hygiene reasons. Herbs and traditional medicines were mainly used to please sexual partner. Strategies to decrease VP appear urgently needed in the Zambian community. PMID- 22041930 TI - The role of multiple identities in adherence to medical appointments among gay/bisexual male adolescents living with HIV. AB - Adolescents living with HIV require engagement with care providers in order to access the critical medical and psychosocial services they need. The current study sought to explore developmental determinants of adherence to medical appointments as one aspect of engagement in care among a geographically diverse sample of 200 gay/bisexual male adolescents (16-24 years) living with HIV, with a specific focus on ethnic identity, sexual orientation identity, and identity as a young man living with HIV. Ethnic identity affirmation (OR = 0.6; 95% CI: 0.3, 0.9), morality of homosexuality (OR = 1.7; 95% CI: 1.2, 2.5), and HIV-positive identity salience (OR = 1.5; 95% CI: 0.9, 2.4) were associated with significantly higher risk for missed appointments in the past 3 months. These findings highlight the importance of attending to developmental factors, such as the development of multiple identities, when attempting to increase engagement in care for gay/bisexual male adolescents living with HIV. PMID- 22041933 TI - Bioluminescent yeast estrogen assay (BLYES) as a sensitive tool to monitor surface and drinking water for estrogenicity. AB - Estrogenic Endocrine Disrupting Chemicals (EDCs) are a concern due to their ubiquity and recognized adverse effects to humans and wildlife. Methods to assess exposure to and associated risks of their presence in aquatic environment are still under development. The aim of this work is to assess estrogenicity of raw and treated waters with different degrees of pollution. Chemical analyses of selected EDCs were performed by liquid chromatography-tandem mass spectrometry, and estrogenic activity was evaluated using in vitro bioluminescent yeast estrogen assay (BLYES). Most raw water samples (18/20) presented at least one EDC and 16 rendered positive in BLYES. When EDCs were detected, the bioassay usually provided a positive response, except when only bisphenol A was detected at low concentrations. The highest values of estrogenic activity were detected in the most polluted sites. The maximum estrogenic activity observed was 8.7 ng equiv. of E2 L(-1). We compared potencies observed in the bioassay to the relative potency of target compounds and their concentrations failed to fully explain the biological response. This indicates that bioassay is more sensitive than the chemical approach either detecting estrogenic target compounds at lower concentrations, other non-target compounds or even synergistic effects, which should be considered on further investigations. We have not detected either estrogenic activity or estrogenic compounds in drinking water. BLYES showed good sensitivity with a detection limit of 0.1 ng equiv. E2 L(-1) and it seems to be a suitable tool for water monitoring. PMID- 22041931 TI - HIV-infected individuals with co-occurring bipolar disorder evidence poor antiretroviral and psychiatric medication adherence. AB - The contribution of bipolar disorder (BD), a prevalent serious mental illness characterized by impulsivity and mood instability, to antiretroviral (ART) and psychiatric medication adherence among HIV-infected (HIV+) individuals is unknown. We examined medication adherence among 44 HIV+/BD+ persons as compared to 33 demographically- and medically-comparable HIV+/BD- persons. Classification of adherent (>= 90%) or non-adherent (<90%) based on proportion of correctly taken doses over 30 days was determined using electronic medication monitoring devices. HIV+/BD+ persons were significantly less likely to be ART adherent (47.7%) as compared to HIV+/BD- (90.9%) persons. Within the HIV+/BD+ group, mean psychiatric medication adherence was significantly worse than ART medication adherence, although there was a significant correlation between ART and psychiatric adherence levels. Importantly, 30-day ART adherence was associated with plasma virologic response among HIV+/BD+ individuals. Given the high overlap of HIV and BD, and the observed medication adherence difficulties for these persons, specialized adherence improvement interventions are needed. PMID- 22041934 TI - CPK12: A Ca2+-dependent protein kinase balancer in abscisic acid signaling. AB - Ca2+ is believed to be a critical second messenger in ABA signal transduction. Ca2+-dependent protein kinases (CDPKs) are the best characterized Ca2+ sensors in plants. Recently, we identified an Arabidopsis CDPK member CPK12 as a negative regulator of ABA signaling in seed germination and post-germination growth, which reveals that different members of the CDPK family may constitute a regulation loop by functioning positively and negatively in ABA signal transduction. We observed that both RNA interference and overexpression of CPK12 gene resulted in ABA-hypersensitive phenotypes in seed germination and post-germination growth, suggesting a high complexity of the CPK12-mediated ABA signaling pathway. CPK12 stimulates a negative ABA-signaling regulator (ABI2) and phosphorylates two positive ABA-signaling regulators (ABF1 and ABF4), which may partly explain the ABA hypersensitivity induced by both downregulation and upregulation of CPK12 expression. Our data indicate that CPK12 appears to function as a balancer in ABA signal transduction in Arabidopsis. PMID- 22041936 TI - Study of lead accumulation in bones of Wistar rats by X-ray fluorescence analysis: aging effect. AB - The accumulation of lead in several bones of Wistar rats with time was determined and compared for the different types of bones. Two groups were studied: a control group (n = 20), not exposed to lead and a contaminated group (n = 30), exposed to lead from birth, first indirectly through mother's milk, and then directly through a diet containing lead acetate in drinking water (0.2%). Rats age ranged from 1 to 11 months, with approximately 1 month intervals and each of the collections had 3 contaminated rats and 2 control rats. Iliac, femur, tibia fibula and skull have been analysed by Energy Dispersive X-ray Fluorescence Technique (EDXRF). Samples of formaldehyde used to preserve the bone tissues were also analysed by Electrothermal Atomic Absorption (ETAAS), showing that there was no significant loss of lead from the tissue to the preservative. The bones mean lead concentration of exposed rats range from 100 to 300 MUg g(-1) while control rats never exceeded 10 MUg g(-1). Mean bone lead concentrations were compared and the concentrations were higher in iliac, femur and tibia-fibula and after that skull. However, of all the concentrations in the different collections, only those in the skull were statistically significantly different (p < 0.05) from the other types of bones. Analysis of a radar chart also allowed us to say that these differences tend to diminish with age. The Spearman correlation test applied to mean lead concentrations showed strong and very strong positive correlations between all different types of bones. This test also showed that mean lead concentrations in bones are negatively correlated with the age of the animals. This correlation is strong in iliac and femur and very strong in tibia-fibula and skull. It was also shown that the decrease of lead accumulation with age is made by three plateaus of accumulation, which coincide, in all analysed bones, between 2nd-3rd and 9th-10th months. PMID- 22041935 TI - Knock-down of protein phosphatase 2A subunit B'gamma promotes phosphorylation of CALRETICULIN 1 in Arabidopsis thaliana. AB - Controlled protein dephosphorylation by protein phosphatase 2A (PP2A) regulates diverse signaling events in plants. Recently, we showed that a specific B'gamma regulatory subunit of PP2A mediates basal repression of immune reactions in Arabidopsis thaliana. Knock-down pp2a-b'gamma mutants display constitutive defense reactions and premature yellowing conditionally under moderate light intensity. Here we show that knock-down of PP2A-B'gamma renders CALRETI CULIN 1 (CRT 1) highly phosphorylated. Calreticulins are ER-resident chaperonins that operate in the unfolded protein response to prevent ER-stress, components of which are differentially regulated at mRNA level in pp2a-b'gamma leaves. We speculate that in dephosphorylated state, CRT 1 promotes the degradation of unfolded proteins in ER. Our findings suggest that in wild type plants, dephosphorylation of CRT 1 is mediated by PP2A-B'gamma dependent signaling effects. In pp2a-b'gamma, strong phosphorylation of CRT 1 may partially imbalance the quality control of protein folding, thereby eliciting ER-stress and premature yellowing in leaves. PMID- 22041937 TI - In search of a vaccine for mouse allergy: significant reduction of Mus m 1 allergenicity by structure-guided single-point mutations. AB - BACKGROUND: Mouse urinary proteins are relevant allergens from mice urine. We used the recombinant protein Mus m 1 as an allergen model to identify if, by altering Mus m 1 architecture via single-point mutations, we could effectively modify its allergenicity. METHODS: Based on structural considerations, we synthesized two single-point mutants, Mus m 1-Y120A and Mus m 1-Y120F, which were expected to harbor large structural alterations. Circular dichroism and fluorescence analysis showed significant conformational rearrangements of the aromatic side chains in the internal cavity of Mus m 1-Y120A when compared to Mus m 1-Y120F and Mus m 1. Evaluation of the allergenic potential of the recombinant molecules was performed in vitro with both immunochemical approaches and assays based on the measurement of basophil degranulation. Moreover, to assess the integrity of the T cell epitopes and as an in vitro measure of immunogenicity, we tested the reactivity of T lymphocytes from subjects allergic to mouse urine against proteins and synthetic peptides encompassing the immunodominant linear epitope containing the mutation. RESULTS: We found that the selected point mutation was able to modulate the protein allergenicity, and to severely impair the recognition of Mus m 1 by IgE, while T cell reactivity was fully maintained. CONCLUSIONS: In silico predicted, minimum selected structural modifications allowed to design one protein with reduced allergenicity and preserved immunogenicity. Structurally guided mutations can direct the design of proteins with reduced allergenicity which can be used as vaccines for a safer and more effective immunotherapy of allergic disorders. PMID- 22041941 TI - Complexes of amino acids with a crown-ether derivative of 4-styrylpyridine. Monotopic or ditopic? AB - An E-4-styrylpyridine derivative endowed with 18-crown-6 as a substituent (E-1) was prepared and evaluated in acetonitrile as a potential ditopic ligand for protonated amino acids. The interactions of E-1 with the protonated amino acid perchlorates, ClO(4)(-) H(3)N(+)(CH(2))(n)COOH (n = 2, 5 and 10, A2, A5 and A10, respectively), were studied by optical methods, (1)H NMR and mass spectroscopy. Complex formation involves coordination of the ammonium ion at the crown ether moiety of E-1. The spectral changes were evaluated by comparison with results obtained on protonation of E-1 with HClO(4) and on association with ammonium perchlorate. Protonation by the protonated amino acid perchlorates was thwarted due to reversal of carboxyl/pyridinium pK(A) order in acetonitrile relative to water. Evidence for ditopic hydrogen bonding complex formation was especially sought for A10 because its CH(2) chain is sufficiently long to bridge the distance between the crown ether and pyridyl N sites of E-1. Despite some subtle hints to the contrary, the absence of NOE interaction between the pyridyl protons of E-1 and the methylene protons of A10 indicates that the E-1.A10 complex is in the main monotopic, as is the case for A2 and A5. The photophysical and photochemical behaviour of the complexes change significantly on protonation by HClO(4). The optical response of E-1 on binding the amino acids as ammonium salts allows convenient monitoring of complex formation. PMID- 22041938 TI - Mechanistic insight into the h(2)o/d (2)o isotope effect in the proton transport of the influenza virus m2 protein. AB - The M2 proton channel is essential for the replication of the flu virus and is a known drug target. The functional mechanism of channel activation and conductance is key to both the basic biology of viral replication and the design of drugs that can withstand mutations. A quantitative model was previously developed for calculating the rate of proton transport through the M2 channel. The permeant proton was assumed to diffuse to the pore, obligatorily bind to the His37 tetrad, and then dissociate and be released to either side of the tetrad. Here the model is used to calculate the effect of a change in solvent from H(2)O to D(2)O on the rate of proton transport. The solvent substitution affects two parameters in the model: the proton diffusion constant and the pK (a) for proton binding to the His37 tetrad. When the known effects on these two parameters are included, the deuterium isotope effect calculated from the model is in quantitatively agreement with experimental results. This strict test of the theoretical model provides strong support for the hypothesis that the permeant proton obligatorily binds to and then unbinds from the His37 tetrad. This putatively essential role of the His37 tetrad in the functional mechanism of the M2 channel makes it a promising target for designing mutation-tolerant drugs. PMID- 22041942 TI - In vitro and in vivo effects of ketamine on generation and function of dendritic cells. AB - The question about how intravenous anesthetic reagents affect the development and function of dendritic cell subsets still has no comprehensive answers. Bone marrow cells differentiated with FMS-like tyrosine kinase 3 ligand in vitro represented the steady-state dendritic cell subsets. The effects of ketamine on the generation and function of dendritic cell subsets were investigated. We found that dendritic cell subsets responded to the anesthetic reagent ketamine in several aspects: 1) The in vitro and in vivo development of plasmacytoid dendritic cells were inhibited by ketamine at high concentrations; 2) The endocytosis of dendritic cells were not influenced by ketamine at concentrations from 50 - 200 uM; 3) The maturation markers of conventional dendritic cells were not changed by ketamine upon LPS or CpG stimulation, although the cytokines mRNA profiles were affected; 4) The allogenic-stimulatory activity of dendritic cells was suppressed by ketamine. In conclusion, ketamine hampered plasmacytoid dendritic cell subset development both in vivo and in vitro. The dendritic cells maturation and downstream responses towards different toll-like receptor stimuli were differently regulated by ketamine treatment. PMID- 22041943 TI - Protection against dopaminergic neurodegeneration in Parkinson's disease-model animals by a modulator of the oxidized form of DJ-1, a wild-type of familial Parkinson's disease-linked PARK7. AB - DJ-1, Parkinson's disease PARK7, acts as an oxidative stress sensor in neural cells. Recently, we identified the DJ-1 modulator UCP0054278 by in silico virtual screening. However, the effect of the peripheral administration of UCP0054278 on an in vivo Parkinson's disease (PD) model is unclear. Therefore, in the present study, we examined the effects of the peripheral administration of UCP0054278 on both 6-OHDA-microinjected rats and rotenone-treated mice as acute and chronic animal models of PD, respectively. The peripheral administration of UCP0054278 prevented 6-OHDA- and rotenone-induced dopaminergic neural cell death and restored the defect in locomotion in these models of PD. In addition, 6-OHDA- or rotenone-induced neural cell death and the production of reactive oxygen species were significantly inhibited by UCP0054278 in normal SH-SY5Y cells, but not in DJ 1-knockdown cells. These results suggest that UCP0054278 interacts with endogenous DJ-1 and then produces antioxidant and neuroprotective responses in both in vivo and in vitro models of PD. The present study raises the possibility that DJ-1 stimulatory modulators, such as UCP0054278, may be a new type of dopaminergic neuroprotective drug for the treatment of PD. PMID- 22041944 TI - Cutaneous diphtheria in a German man with travel history. PMID- 22041945 TI - Yoga for chronic low back pain: a randomized trial. AB - BACKGROUND: Previous studies indicate that yoga may be an effective treatment for chronic or recurrent low back pain. OBJECTIVE: To compare the effectiveness of yoga and usual care for chronic or recurrent low back pain. DESIGN: Parallel group, randomized, controlled trial using computer-generated randomization conducted from April 2007 to March 2010. Outcomes were assessed by postal questionnaire. (International Standard Randomised Controlled Trial Number Register: ISRCTN 81079604) SETTING: 13 non-National Health Service premises in the United Kingdom. PATIENTS: 313 adults with chronic or recurrent low back pain. INTERVENTION: Yoga (n = 156) or usual care (n = 157). All participants received a back pain education booklet. The intervention group was offered a 12-class, gradually progressing yoga program delivered by 12 teachers over 3 months. MEASUREMENTS: Scores on the Roland-Morris Disability Questionnaire (RMDQ) at 3 (primary outcome), 6, and 12 (secondary outcomes) months; pain, pain self efficacy, and general health measures at 3, 6, and 12 months (secondary outcomes). RESULTS: 93 (60%) patients offered yoga attended at least 3 of the first 6 sessions and at least 3 other sessions. The yoga group had better back function at 3, 6, and 12 months than the usual care group. The adjusted mean RMDQ score was 2.17 points (95% CI, 1.03 to 3.31 points) lower in the yoga group at 3 months, 1.48 points (CI, 0.33 to 2.62 points) lower at 6 months, and 1.57 points (CI, 0.42 to 2.71 points) lower at 12 months. The yoga and usual care groups had similar back pain and general health scores at 3, 6, and 12 months, and the yoga group had higher pain self-efficacy scores at 3 and 6 months but not at 12 months. Two of the 157 usual care participants and 12 of the 156 yoga participants reported adverse events, mostly increased pain. LIMITATION: There were missing data for the primary outcome (yoga group, n = 21; usual care group, n = 18) and differential missing data (more in the yoga group) for secondary outcomes. CONCLUSION: Offering a 12-week yoga program to adults with chronic or recurrent low back pain led to greater improvements in back function than did usual care. PRIMARY FUNDING SOURCE: Arthritis Research UK. PMID- 22041946 TI - Net clinical benefit of adding clopidogrel to aspirin therapy in patients with atrial fibrillation for whom vitamin K antagonists are unsuitable. AB - BACKGROUND: Adding clopidogrel to aspirin therapy reduces stroke in patients with atrial fibrillation (AF) but increases hemorrhage. OBJECTIVE: To quantify the net benefit of adding clopidogrel to aspirin therapy, accounting for differences in clinical significance between ischemic and hemorrhagic events. DESIGN: Observational cohort study to assign the relative weighting of events and post hoc analysis of randomized trial data to assess net benefit of dual antiplatelet therapy in the ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) clinical trials. SETTING: Global randomized clinical trial. PATIENTS: 10,041 patients with AF, 7554 of whom were not candidates for warfarin therapy. MEASUREMENTS: Ischemic events (ischemic stroke or myocardial infarction) and hemorrhagic events (hemorrhagic stroke or subdural or extracranial bleeding), weighted by the hazard ratio for death (or death or disability) after an event relative to death (or death or disability) after ischemic stroke. The net clinical benefit of dual antiplatelet therapy in the ACTIVE A trial participants was defined as the sum of weighted event incidence with dual antiplatelet therapy subtracted from the sum of weighted event incidence on control treatment, expressed as ischemic stroke equivalents prevented per 100 patients years. RESULTS: Adding clopidogrel to aspirin therapy prevented 0.57 ischemic stroke equivalent (95% CI, -0.12 to 1.24) per 100 patient years of treatment when weighted by hazard for death after ischemia or hemorrhage and 0.67 ischemic stroke equivalent (CI, -0.03 to 1.18) when weighted by death or disability after ischemia or hemorrhage. LIMITATION: No attempt was made to relate deaths used for weighting to events; disability data were missing for more than one half of patients. CONCLUSION: Adding clopidogrel to aspirin therapy resulted in a modest net benefit among patients with AF for whom warfarin was unsuitable. The benefit would probably be clinically relevant for some patients, but estimates could not exclude the possibility of either no benefit or very small harm in this population. PRIMARY FUNDING SOURCE: Bristol-Myers Squibb and sanofi-aventis. PMID- 22041947 TI - Safety of screening procedures with hand-held metal detectors among patients with implanted cardiac rhythm devices: a cross-sectional analysis. AB - BACKGROUND: Case reports suggest that the hand-held metal detectors used for security screening generate electromagnetic fields that may interfere with pacemaker and implantable cardioverter-defibrillator (ICD) function. OBJECTIVE: To assess changes in function of pacemakers and ICDs after exposure to hand-held metal detectors. DESIGN: Cross-sectional study. SETTING: Two medical centers in Europe. PATIENTS: 388 patients (209 with pacemakers and 179 with ICDs) presenting for routine follow-up of device function between September 2009 and December 2010. MEASUREMENTS: Abnormalities on electrocardiography suggestive of rhythm device malfunction (pacing inhibition, loss of capture, inappropriate mode switch, ventricular oversensing, and spontaneous reprogramming) after 30 seconds of exposure to 2 widely used hand-held metal detectors with a maximal electromagnetic flux density of 6.3 uT. RESULTS: No change in device function, including pacing or sensing abnormalities or device reprogramming, was observed in any patient. LIMITATIONS: The study included a convenience sample of patients, and the number of different device models tested was small. Testing was conducted in 2 clinic settings. CONCLUSION: Hand-held metal detectors did not affect the function of pacemakers or ICDs in this sample. The use of hand-held metal detectors for security screening is probably safe for patients with pacemakers and ICDs, but these findings require confirmation. PRIMARY FUNDING SOURCE: None. PMID- 22041948 TI - Enhancing communication between oncologists and patients with a computer-based training program: a randomized trial. AB - BACKGROUND: Quality cancer care requires addressing patients' emotions, which oncologists infrequently do. Multiday courses can teach oncologists skills to handle emotion; however, such workshops are long and costly. OBJECTIVE: To test whether a brief, computerized intervention improves oncologist responses to patient expressions of negative emotion. DESIGN: Randomized, controlled, parallel group trial stratified by site, sex, and oncologic specialty. Oncologists were randomly assigned to receive a communication lecture or the lecture plus a tailored CD-ROM. (ClinicalTrials.gov registration number: NCT00276627) SETTING: Oncology clinics at a comprehensive cancer center and Veterans Affairs Medical Center in Durham, North Carolina, and a comprehensive cancer center in Pittsburgh, Pennsylvania. PARTICIPANTS: 48 medical, gynecologic, and radiation oncologists and 264 patients with advanced cancer. INTERVENTION: Oncologists were randomly assigned in a 1:1 ratio to receive an interactive CD-ROM about responding to patients' negative emotions. The CD-ROM included tailored feedback on the oncologists' own recorded conversations. MEASUREMENTS: Postintervention audio recordings were used to identify the number of empathic statements and responses to patients' expressions of negative emotion. Surveys evaluated patients' trust in their oncologists and perceptions of their oncologists' communication skills. RESULTS: Oncologists in the intervention group used more empathic statements (relative risk, 1.9 [95% CI, 1.1 to 3.3]; P = 0.024) and were more likely to respond to negative emotions empathically (odds ratio, 2.1 [CI, 1.1 to 4.2]; P = 0.028) than control oncologists. Patients of intervention oncologists reported greater trust in their oncologists than did patients of control oncologists (estimated mean difference, 0.1 [CI, 0.0 to 0.2]; P = 0.036). There was no significant difference in perceptions of communication skills. LIMITATIONS: Long-term effects were not examined. The findings may not be generalizable outside of academic medical centers. CONCLUSION: A brief computerized intervention improves how oncologists respond to patients' expressions of negative emotions. PRIMARY FUNDING SOURCE: National Cancer Institute. PMID- 22041949 TI - Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians Clinical Practice Guideline. AB - BACKGROUND: Venous thromboembolism prophylaxis has been recommended for nonsurgical patients, but its effectiveness remains uncertain. PURPOSE: To assess the benefits and harms of prophylaxis in hospitalized adult medical patients and those with acute stroke. DATA SOURCES: MEDLINE and the Cochrane Library from 1950 through April 2011, reference lists, and study authors. STUDY SELECTION: English language randomized trials were included if they provided clinical outcomes and evaluated therapy with low-dose heparin or related agents or mechanical measures compared with placebo, no treatment, or other active prophylaxis in the target population. DATA EXTRACTION: Two independent investigators extracted data on study characteristics and clinical outcomes up to 120 days after randomization. The primary outcome was total mortality. DATA SYNTHESIS: In medical patients, heparin prophylaxis did not reduce total mortality but did result in fewer pulmonary embolisms (PEs) (odds ratio [OR], 0.69 [95% CI, 0.52 to 0.90], but with evidence of publication bias) and an increase in all bleeding events (risk ratio [RR], 1.34 [CI, 1.08 to 1.66]). Heparin prophylaxis had no statistically significant effect on any outcome in patients with acute stroke except for an increase in major bleeding events (OR, 1.66 [CI, 1.20 to 2.28]). When trials of medical patients and those with stroke were considered together (18 studies; 36,122 patients), heparin prophylaxis reduced the incidence of PE (OR, 0.70 [CI, 0.56 to 0.87]; absolute reduction, 3 events per 1000 patients treated [CI, 1 to 5 events]) but increased the incidence of all bleeding (RR, 1.28 [CI, 1.05 to 1.56]) and major bleeding events (OR, 1.61 [CI, 1.23 to 2.10]), with an absolute increase of 9 bleeding events per 1000 patients treated (CI, 2 to 18 events), 4 of which were major (CI, 1 to 7 events). A reduction in total mortality approached statistical significance (RR, 0.93 [CI, 0.86 to 1.00]; P = 0.056; absolute decrease, 6 deaths per 1000 patients treated [CI, 0 to 11 deaths]). No statistically significant differences in clinical outcomes were observed in the 14 trials that compared unfractionated heparin with low-molecular-weight heparin. No improvements in clinical outcomes were seen in the 3 studies of mechanical prophylaxis in patients with stroke, but more patients had lower-extremity skin damage (RR, 4.02 [CI, 2.34 to 6.91])-an increase of 39 events per 1000 patients treated (CI, 17 to 77 events). LIMITATION: Non-English-language studies were not included, but these were few and small. CONCLUSION: Heparin prophylaxis had no significant effect on mortality, may have reduced PE in medical patients and all patients combined, and led to more bleeding and major bleeding events, thus resulting in little or no net benefit. No differences in benefits or harms were found according to type of heparin used. Mechanical prophylaxis provided no benefit and resulted in clinically important harm to patients with stroke. PRIMARY FUNDING SOURCE: American College of Physicians. PMID- 22041950 TI - Emerging magnetic resonance imaging technologies for musculoskeletal imaging under loading stress: scope of the literature. AB - Imaging under loading stress is hypothesized to improve the diagnostic value of magnetic resonancel imaging (MRI) for musculoskeletal conditions. This article reviews 57 studies about MRI under physiologic loading stress performed in an upright or sitting position or under axial loading by using a compression device. The most commonly imaged regions were the spine (33 studies) and knee (13 studies). Most studies had a cross-sectional (n = 37) or case-control (n = 13) design and reported on anatomical measurements rather than patient-relevant end points. Studies were generally small: The median (25th, 75th percentile) number of case patients was 26 (17, 45), and the median (25th, 75th percentile) number of control participants was 13 (12, 20 for case-control studies). Fifteen of 57 studies used at least 2 imaging tests and reported on diagnostic or patient relevant outcomes but did not report meaningful information on the relative performance of the tests. In 10 studies that included information on adverse effects, 5% to 15% of participants reported new-onset or worsening pain and neuropathy during MRI under loading stress. Overall, evidence is insufficient to support the clinical utility of MRI under loading stress for musculoskeletal conditions. PMID- 22041951 TI - Venous thromboembolism prophylaxis in hospitalized patients: a clinical practice guideline from the American College of Physicians. AB - DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on prophylaxis of venous thromboembolism for hospitalized nonsurgical patients (medical patients and patients with acute stroke). METHODS: This guideline is based on published literature on the topic from 1950 through April 2011 that was identified by using MEDLINE, the Cochrane Library, and reference lists of pertinent randomized trials and systematic reviews to identify additional reports. Searches were limited to randomized trials and English-language publications. The primary outcome for this guideline was total mortality up to 120 days after randomization. Secondary outcomes included symptomatic deep venous thrombosis; all pulmonary embolisms; fatal pulmonary embolism; all bleeding events; major bleeding events; and, for mechanical prophylaxis, effects on skin. This guideline grades the evidence and recommendations by using the ACP's clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends assessment of the risk for thromboembolism and bleeding in medical (including stroke) patients prior to initiation of prophylaxis of venous thromboembolism (Grade: strong recommendation, moderate quality evidence). RECOMMENDATION 2: ACP recommends pharmacologic prophylaxis with heparin or a related drug for venous thromboembolism in medical (including stroke) patients unless the assessed risk for bleeding outweighs the likely benefits (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 3: ACP recommends against the use of mechanical prophylaxis with graduated compression stockings for prevention of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence). POLICY IMPLICATION: ACP does not support the application of performance measures in medical (including stroke) patients that promotes universal venous thromboembolism prophylaxis regardless of risk. PMID- 22041952 TI - Retainer medicine: an ethically legitimate form of practice that can improve primary care. AB - Retainer medicine has become an important yet controversial form of primary care practice in the United States, coming under attack for its purported failure to measure up to professional ethics. Critics opine that retainer medicine obstructs professional commitments to health care access and social justice. Some ethicists urge that society should restrict or ban retainer medicine; professional organizations have yet to take a stand. The authors believe that retainer medicine is compatible with professional ethics and will more likely aid in solving the difficulties facing primary care rather than add to them. Although professional ethics should evolve to address new conditions, a condemnation of retainer medicine is warranted neither by traditional ethical precepts nor by contemporary developments in medical ethics. Any move to sanction retainer medicine under the banner of professionalism or professional ethics will be counterproductive. The primary care shortage will only get worse if physicians in retainer practice leave primary care altogether, a likely outcome of legal or professional condemnation of retainer practice. PMID- 22041953 TI - Selecting the optimal stroke prevention therapy in atrial fibrillation. PMID- 22041954 TI - Evidence-based performance measures: preventing unintended consequences of quality measurement. PMID- 22041955 TI - Retainer medicine: why not for all? PMID- 22041956 TI - Discovery at the bedside. PMID- 22041957 TI - Chris' tears. PMID- 22041958 TI - Prognosis. PMID- 22041959 TI - Thyrotoxicosis: a lesson from the slaughterhouse. PMID- 22041960 TI - Human diphtheria infection from a cat bite. PMID- 22041961 TI - Episodic monocular vision loss after implantation of a vagal nerve stimulator. PMID- 22041962 TI - False-positive blood glucose and ketone values with lightening cream. PMID- 22041963 TI - Pharyngeal painful tonic spasms: paroxysmal painful swallowing. PMID- 22041964 TI - Summaries for patients: Are hand-held metal detectors used in airports safe for people with pacemakers and defibrillators? PMID- 22041965 TI - Summaries for patients: Preventing venous thromboembolism in hospitalized patients: recommendations from the American College of Physicians. PMID- 22041966 TI - In the clinic. Atopic dermatitis (eczema). AB - This issue provides a clinical overview of atopic dermatitis (exzema) focusing on prevention, diagnosis, treatment, practice improvement, and patient information. Readers can complete the accompanying CME quiz for 1.5 credits. Only ACP members and individual subscribers can access the electronic features of In the Clinic. Non-subscribers who wish to access this issue of In the Clinic can elect "Pay for View." Subscribers can receive 1.5 category 1 CME credits by completing the CME quiz that accompanies this issue of In the Clinic. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including PIER (Physicians' Information and Education Resource) and MKSAP (Medical Knowledge and Self Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing division and with assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult www.acponline.org, http://pier.acponline.org, and other resources referenced within each issue of In the Clinic. PMID- 22041967 TI - Sirtuins in neurodegenerative diseases: a biological-chemical perspective. AB - Sirtuins, commonly known as NAD(+)-dependent class III histone deacetylase enzymes, have been extensively studied to evaluate their potential role in different disease states. Based on the published literature, sirtuins have been implicated in providing a myriad of intrinsic and extrinsic biological effects, which in turn may play an important role in the treatment of various disorders such as type II diabetes, obesity, cancer, aging and different neurodegenerative diseases. In particular, a number of studies have unequivocally supported the idea of sirtuins having therapeutic potential in neurodegenerative diseases such as stroke, ischemic brain injury, Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. To exploit the therapeutic potential of sirtuins, their manipulation in terms of development of small-molecule modulators, inhibitors and analogs has increased dramatically since their inception, in both scientific and industrial worlds. Studies on the structure and catalytic core of sirtuins along with chemical mechanisms and substrate specificity have provided important input into the design and synthesis of sirtuin modulators. To study the role of sirtuins in the biological system, it has become extremely important to understand the molecular and chemical structure of sirtuins. In this review, we have discussed the biological role of sirtuins in various neurodegenerative diseases, and also provided an insight into their chemical structure. PMID- 22041968 TI - Distinct Young's modulus of nanostructured materials in comparison with nanocrystals. AB - Young's modulus (Y) of nanostructured materials (NSs) free of porosity is modeled with regard to the coordination number imperfection at grain boundaries. In light of it, Y of NSs is suppressed substantially in the whole solid temperature range, differing from the case of nanocrystals (NCs) where Y is enhanced at lower temperature (T) but weakened at higher T. It is found that, similar to NCs, the thermally-driven decline associated with the melting point depression plays an increasing role in suppressing Y of NSs on raising T. On the other hand, the lattice expansion and the bond weakening lead to a further suppression in Y of NSs independent of T, while the lattice contraction and the reinforced bonding strength result in an enhancement in Y of NCs, which should be responsible for the distinction in Y between NSs and NCs. The established functions were supported by available experimental and computer simulation results. PMID- 22041969 TI - Effects of neostigmine on bronchoconstriction with continuous electrical stimulation in rats. AB - PURPOSE: When neostigmine is used to reverse muscle relaxants in patients with asthma without signs of airway inflammation, asthma attack is occasionally encountered. It is likely that abnormally increased electrical impulses traveling from the brain through cholinergic nerves to airway smooth muscles may be one of the pathogeneses of asthma attack. We applied continuous electrical field stimulation (c-EFS) or continuous electrical stimulation (c-ES) of low frequency to the vagal nerve of the rat in vitro and in vivo to determine the role of cholinergic nerve activation in inducing airway constriction. METHODS: Fifty seven male Wistar rats were used. In an in vitro study we examined whether tetrodotoxin (TTX), an Na(+)-channel blocker, 4-DAMP, a muscarinic M(3) receptor antagonist, or neostigmine could affect c-EFS-induced contraction of the tracheal ring. In an in vivo study, we examined whether c-ES of the vagal nerve could increase maximum airway pressure (P (max)) and whether neostigmine could potentiate c-ES-induced P (max). RESULTS: TTX and 4-DAMP completely inhibited c EFS-induced contraction whereas neostigmine potentiated c-EFS-induced contraction dose-dependently. P (max) was not increased by neostigmine. P (max) was not increased by 2-Hz c-ES, but was increased by the addition of neostigmine. P (max) was increased by 5-Hz c-ES, and further increased by the addition of neostigmine. CONCLUSION: The contractile response of the tracheal ring to c-EFS is potentiated by neostigmine. P (max) is increased by c-ES of the vagal nerve, and is potentiated by neostigmine. These data suggest that increased activity of the cholinergic nerve could be involved in asthma attack. PMID- 22041970 TI - Safety and efficacy of oral rehydration therapy until 2 h before surgery: a multicenter randomized controlled trial. AB - PURPOSE: In many countries, patients are generally allowed to have clear fluids until 2-3 h before surgery. In Japan, long preoperative fasting is still common practice. To shorten the preoperative fasting period in Japan, we tested the safety and efficacy of oral rehydration therapy until 2 h before surgery. METHODS: Three hundred low-risk patients scheduled for morning surgery in six university-affiliated hospitals were randomly assigned to an oral rehydration solution (ORS) group or to a fasting group. Patients in the ORS group consumed up to 1,000 ml of ORS containing balanced glucose and electrolytes: 500 ml between 2100 the night before surgery and the time they woke up the next morning and 500 ml during the morning of surgery until 2 h before surgery. Patients in the fasting group started fasting at 2100 the night before surgery. Primary endpoints were gastric fluid volume and pH immediately after anesthesia induction. Several physiological measures of hydration and electrolytes including the fractional excretion of sodium (FENa) and the fractional excretion of urea nitrogen (FEUN) were also evaluated. RESULTS: Mean (SD) gastric fluid volume immediately after anesthesia induction was 15.1 (14.0) ml in the ORS group and 17.5 (23.2) ml in the fasting group (P = 0.30). The mean difference between the ORS group and fasting group was -2.5 ml. The 95% confidence interval ranged from -7.1 to +2.2 ml and did not include the noninferior limit of +8 ml. Mean (SD) gastric fluid pH was 2.1 (1.9) in the ORS group and 2.2 (2.0) in the fasting group (P = 0.59). In the ORS group, mean FENa and FEUN immediately after anesthesia induction were both significantly greater than those in the fasting group (P < 0.001 for both variables). The ORS group reported they had been less thirsty and hungry before surgery (P < 0.001, 0.01). CONCLUSIONS: Oral rehydration therapy until 2 h before surgery is safe and feasible in the low-risk Japanese surgical population. Physicians are encouraged to use this practice to maintain the amount of water in the body and electrolytes and to improve the patient's comfort. PMID- 22041971 TI - Peripheral nerve block in a patient with amyotrophic lateral sclerosis. PMID- 22041972 TI - Trastuzumab treatment beyond progression in advanced breast cancer: patterns of care in six Swiss breast cancer centers. AB - BACKGROUND: Trastuzumab is an established treatment for HER2-positive breast cancer (BC). We analyzed Swiss patterns of care in patients with HER2-positive BC after disease progression on trastuzumab-containing therapy for metastatic BC (MBC). PATIENTS AND METHODS: A retrospective analysis was performed in six Swiss BC centers. Patients with HER2-positive MBC treated with at least one infusion of trastuzumab for advanced disease between January 2006 and December 2007 were identified. Treatment patterns in first and further lines were analyzed. RESULTS: All of the 72 identified patients received trastuzumab as their first palliative anti-HER2 therapy, either as monotherapy (n = 23) or in combination with chemotherapy (typically taxane or vinorelbine; n = 49). Median time to progression was 8.1, 8.0 and 7.9 months in the monotherapy, trastuzumab-taxane and trastuzumab-vinorelbine cohorts, respectively. After progression on first line anti-HER2 therapy, trastuzumab was continued in 67 of 68 patients who received further therapy. One patient received second-line lapatinib plus capecitabine. The median duration of anti-HER2 therapy was 20 months. Patients received a median of 4 lines of anti-HER2 therapy. CONCLUSIONS: Durable responses were achieved with repeated exposure to anti-HER2 therapy. In a selected patient population, trastuzumab monotherapy appears to be a reasonable first-line treatment option. PMID- 22041973 TI - Structure, regulation and function of ghrelin. AB - Ghrelin is a stomach hormone that acts as an endogenous ligand of orphan G protein-coupled receptor. Ghrelin is a 28-amino acid peptide existing in two major forms: n-octanoyl-modified ghrelin, which possesses an n-octanoyl modification on serine-3 and des-acyl ghrelin. Fatty acid modification of ghrelin is essential for ghrelin-induced growth hormone release from the pituitary and appetite stimulation. This acyl-modification of ghrelin is catalysed by ghrelin-O acyl transferase recently identified. Despite the number of innovative advancements in this field of research, there are still many aspects of ghrelin function and biosynthesis process that remain to be clarified. Here, we review the current understanding of the structure, regulation and function of ghrelin; this review is intended for researchers who will be involved in this field in the future. PMID- 22041974 TI - Oral biofilm analysis of palatal expanders by fluorescence in-situ hybridization and confocal laser scanning microscopy. AB - Confocal laser scanning microscopy (CLSM) of natural heterogeneous biofilm is today facilitated by a comprehensive range of staining techniques, one of them being fluorescence in situ hybridization (FISH). We performed a pilot study in which oral biofilm samples collected from fixed orthodontic appliances (palatal expanders) were stained by FISH, the objective being to assess the three dimensional organization of natural biofilm and plaque accumulation. FISH creates an opportunity to stain cells in their native biofilm environment by the use of fluorescently labeled 16S rRNA-targeting probes. Compared to alternative techniques like immunofluorescent labeling, this is an inexpensive, precise and straightforward labeling technique to investigate different bacterial groups in mixed biofilm consortia. General probes were used that bind to Eubacteria (EUB338 + EUB338II + EUB338III; hereafter EUBmix), Firmicutes (LGC354 A-C; hereafter LGCmix), and Bacteroidetes (Bac303). In addition, specific probes binding to Streptococcus mutans (MUT590) and Porphyromonas gingivalis (POGI) were used. The extreme hardness of the surface materials involved (stainless steel and acrylic resin) compelled us to find new ways of preparing the biofilm. As these surface materials could not be readily cut with a cryotome, various sampling methods were explored to obtain intact oral biofilm. The most workable of these approaches is presented in this communication. Small flakes of the biofilm-carrying acrylic resin were scraped off with a sterile scalpel, taking care not to damage the biofilm structure. Forceps were used to collect biofilm from the steel surfaces. Once collected, the samples were fixed and placed directly on polysine coated glass slides. FISH was performed directly on these slides with the probes mentioned above. Various FISH protocols were combined and modified to create a new protocol that was easy to handle. Subsequently the samples were analyzed by confocal laser scanning microscopy. Well-known configurations could be visualized, including mushroom-style formations and clusters of coccoid bacteria pervaded by channels. In addition, the bacterial composition of these typical biofilm structures were analyzed and 2D and 3D images created. PMID- 22041975 TI - Expanded endonasal endoscopic approach for resection of a skull base low-grade smooth muscle neoplasm. AB - Benign smooth muscle tumors rarely occur in the head and neck and, to the best of our knowledge, have not been reported in the pterygopalatine fossa. In this report, we describe a 15-year-old adolescent who presented with facial pain and was found to have a large skull base tumor centered in the pterygopalatine fossa. The patient underwent an expanded endonasal endoscopic approach for complete resection of this lesion with resolution of his symptoms. Pathology revealed a well-differentiated smooth muscle neoplasm consistent with a leiomyoma. This case adds to the growing body of literature supporting a role for endoscopic procedures in the treatment of skull base pathologies in pediatric patients. PMID- 22041976 TI - Is the presence or absence of tumour necrosis a significant predictor of survival in renal cell cancer? AB - OBJECTIVE: Currently when renal cancer pathology is assessed the presence or absence of necrosis is simply reported. It has been suggested that a presence or absence response ignores heterogeneity and a classification based on the extent of necrosis involvement would aid prognostic value in cancer-specific survival. The aim of this study was to determine whether a quantitative assessment of tumour necrosis would provide additional prognostic information. METHODS: We studied the pathological features and cancer-specific survival of 47 patients with renal cancer undergoing surgery with curative intent. A quantitative assessment of tumour necrosis was compared to the presence or absence of necrosis. RESULTS: Tumour necrosis was present in 27 of 47 cases. A simple assessment of the presence or absence was not associated with cancer-specific survival (p = 0.052). When assessed quantitatively, tumour necrosis was associated with decreased cancer-specific survival (p < 0.001). A 2-tiered assessment, <25% and >25% involvement of necrosis, was further utilised and shown to predict cancer-specific survival (p < 0.001). On multivariate analysis, using this 2-tiered assessment of <25% and >25% involvement of necrosis was retained as a significant independent factor for cancer-specific survival (HR 11.84, 95% CI 3.81-36.75, p < 0.001). CONCLUSION: A simple assessment of the presence/absence of tumour necrosis is reported to be a prognostic factor in renal cell cancer. In this study, the presence/absence was not shown to be a significant prognostic marker of cancer-specific survival. However, a more accurate quantitative assessment of tumour necrosis, whereby a 2-tiered response is still utilised, but basing this on <25% and >25% involvement of necrosis was statistically significant and independent in predicting cancer-specific survival. PMID- 22041977 TI - Verminephrobacter aporrectodeae sp. nov. subsp. tuberculatae and subsp. caliginosae, the specific nephridial symbionts of the earthworms Aporrectodea tuberculata and A. caliginosa. AB - Clone library-based studies have shown that almost all lumbricid earthworm species harbour host-specific symbiotic bacteria belonging to the novel genus Verminephrobacter in their nephridia (excretory organs). To date the only described representative from this genus is Verminephrobacter eiseniae, the specific symbiont of the earthworm Eisenia fetida. In this study two novel rod shaped, non-endosporeforming, betaproteobacterial symbionts were isolated from the nephridia of two closely related earthworm species. Both isolates were affiliated with the genus Verminephrobacter by 16S rRNA gene sequence analysis. Similarly to V. eiseniae, the two isolates grew aerobically with a preference for low oxygen concentrations on a range of sugars, fatty acids and amino acids and fermentatively on glucose and pyruvate. These phenotypes match well with the conditions reported or inferred for the nephridial environment. Based on 16S rRNA gene similarity, DNA-DNA hybridization value and phenotypic characteristics the two isolates are clearly distinct from V. eiseniae. Phenotypic characteristics could not clearly differentiate the two strains as separate species but a low DNA DNA hybridization value of 57.3%, their earthworm host specificity, differing temperature ranges and pH optima suggest that they represent two subspecies of a novel species of Verminephrobacter. For this species, the name V. aporrectodeae sp. nov. is proposed, with the two subspecies V. aporrectodeae subsp. tuberculatae (type strain, At4(T) = DSM 21361(T) = LMG 25313(T)) and V. aporrectodeae subsp. caliginosae (type strain, Ac9(T) = DSM 21895(T) = LMG 25312(T)) isolated from the nephridia of the earthworms Aporrectodea tuberculata and A. caliginosa, respectively. PMID- 22041978 TI - Systematics of prokaryotes: the state of the art. AB - The term taxonomy is often used synonymously with systematics but it should be regarded more as a specific part of the latter and comprises the orderly arrangements of (defined) units in addition to the nomenclature, i.e. labelling of these units defined by classification, and also identification of these units defined by classification and labeled by nomenclature. Similar to all biological disciplines, taxonomic approaches in microbiology aim at the establishment of a system that mirrors the "order in nature" as closely as possible with the ultimate goal to describe the whole evolutionary order back to the origin of life. With the recognition of molecular markers present in all organisms (here in particular the small subunit rRNAs, ssRNSs), the achievement of this goal has become more and more feasible and the generation of gene and increasing numbers of genome sequences allow nowadays the generation of large amounts of data and often a very detailed insight into the genetic potential of prokaryotes. The possibility to generate whole genome sequences in a very short period of time leads to a strong tendency to base the taxonomic system more and more on sequence data. However, a comprehensive understanding of all the information behind sequence data is lagging far behind their accumulation. Genes and genomes may (or may not) function only in a given "environment", with the cell as basic entity for the display of this potential. Prokaryotic taxonomy still has its focus on the whole organism. In this context, natural selection drives evolution selecting the existing phenotypes and it is the phenotype that "exhibits" this process both in a given cellular and also environmental context. The term polyphasic taxonomy, which was coined almost 40 years ago and aimed at the integration of many levels of information (from molecular to ecological data) thereby allowing a more holistic view, should be revisited in the light of the enormous potential of the novel information associated with large data sets. PMID- 22041979 TI - The physiological characteristics of the yeast Dekkera bruxellensis in fully fermentative conditions with cell recycling and in mixed cultures with Saccharomyces cerevisiae. AB - The yeast Dekkera bruxellensis plays an important role in industrial fermentation processes, either as a contaminant or as a fermenting yeast. In this study, an analysis has been conducted of the fermentation characteristics of several industrial D. bruxellensis strains collected from distilleries from the Southeast and Northeast of Brazil, compared with Saccharomyces cerevisiae. It was found that all the strains of D. bruxellensis showed a lower fermentative capacity as a result of inefficient sugar assimilation, especially sucrose, under anaerobiosis, which is called the Custer effect. In addition, most of the sugar consumed by D. bruxellensis seemed to be used for biomass production, as was observed by the increase of its cell population during the fermentation recycles. In mixed populations, the surplus of D. bruxellensis over S. cerevisiae population could not be attributed to organic acid production by the first yeast, as previously suggested. Moreover, both yeast species showed similar sensitivity to lactic and acetic acids and were equally resistant to ethanol, when added exogenously to the fermentation medium. Thus, the effects that lead to the employment of D. bruxellensis in an industrial process and its effects on the production of ethanol are multivariate. The difficulty of using this yeast for ethanol production is that it requires the elimination of the Custer effect to allow an increase in the assimilation of sugar under anaerobic conditions. PMID- 22041980 TI - Kinetics of exercise-induced neural activation; interpretive dilemma of altered cerebral perfusion. AB - Neural activation decreases cerebral deoxyhaemoglobin (HHb(C)) and increases oxyhaemoglobin concentration (O(2)Hb(C)). In contrast, patients who present with restricted cerebral blood flow, such as those suffering from cerebral ischaemia or Alzheimer's disease, and during the course of ageing the converse occurs, in that HHb(C) increases and O(2)Hb(C) decreases during neural activation. In the present study, we examined the interpretive implications of altered exercise induced cerebral blood flow for cortical oxygenation in healthy subjects. Both O(2)Hb(C) and HHb(C) (prefrontal cortex) were determined in 11 healthy men using near-infrared spectroscopy (NIRS). Middle cerebral artery mean blood velocity (MCA V(mean)) was determined via transcranial Doppler ultrasonography. Measurements were performed during contralateral hand-grip exercise during suprasystolic bilateral thigh-cuff occlusion (Cuff+) and within 2 s of cuff release (Cuff-) for the acute manipulation of cerebral perfusion. During Cuff+, both MCA V(mean) and O(2)Hb(C) increased during exercise, whereas HHb(C) decreased. In contrast, the opposite occurred during the Cuff- manipulation. These findings highlight the inverse relationship between cerebral blood flow and cerebral oxygenation as determined by NIRS, which has interpretive implications for the kinetics underlying exercise-induced neural activation. PMID- 22041981 TI - Dopaminergic modulation of exercise hyperpnoea via D(2) receptors in mice. AB - Dopamine is related to behaviour (including arousal, motivation and motor control of locomotion), and its turnover in the brain is increased during exercise. We examined the hypothesis that dopamine D(2) receptors contribute to exercise hyperpnoea via central neural pathways using the D(2)-like receptor antagonist, raclopride. We simultaneously measured ventilation and pulmonary gas exchange for the first time in mice. Mice injected with saline and raclopride (2 mg (kg body weight)(-1); i.p.) were compared for respiratory responses to constant-load exercise at 6 m min(-1). Each mouse was set in an airtight treadmill chamber. In the resting state, raclopride-treated mice had reduced respiratory frequency (f(R)) and minute ventilation (V) compared with saline-treated mice, but arterial P(CO(2)) and pulmonary gas exchange were not affected, showing that alveolar ventilation was maintained. Inhalation of hyperoxic gas maintained V in saline treated mice, and hypercapnic ventilatory responses between the two groups were similar. Treadmill exercise produced an abrupt increase in V to a maximal level within 1 min and declined to a steady-state level in both groups. Raclopride treated mice had reduced f(R) and V compared with saline-treated mice during steady states, but showed a similar increase in f(R) and V at exercise onset. Minute ventilation in the steady state was controlled, along with the increase in pulmonary O(2) uptake in both groups, but was lowered in raclopride-treated mice. Thus, D(2) receptors participate in resting breathing patterns to raise f(R) and exercise hyperpnoea in the steady state, probably through behavioural control and not central motor command, at exercise onset. PMID- 22041982 TI - Cost-free and sustainable incentive increases healthy eating decisions during elementary school lunch. AB - We aimed to develop a cost-free and sustainable program to influence healthier eating decisions during elementary school lunch. Baseline food and beverage choices were assessed for 9 days during lunch service at two racially and economically diverse elementary schools in Spartanburg County, SC, USA. After being informed that the labeled items on the daily lunch menu represented the healthiest choice, students were allowed to ring a call bell in the cafeteria for public recognition when they chose all of the identified healthiest food and beverage items during lunch service. Using menus matched to the baseline phase, food and beverage choices were measured during a 9-day intervention phase. After 30 days, food and beverage choices were reassessed during a 3-day follow-up phase. Healthiest food & beverage choices increased 49% with >60% of students choosing non-flavored milk over flavored milk during the intervention phase. There was no difference in the success of the program between the two schools. The program continued and healthy eating decisions were significantly sustained at a 30-day follow-up assessment. Public recognition through bell ringing appears to be an effective practice to sustain increases in healthy eating decisions during elementary school lunch and warrants expansion to larger scale, longitudinal trials. PMID- 22041983 TI - Recapitulation of genome-wide association studies on body mass index in the Korean population. AB - Obesity is a risk factor for multiple disorders such as diabetes and cardiovascular disease. Recently, a genome-wide association study for body mass index (BMI) was conducted in 249 796 individuals of European ancestry by the Genetic Investigation of Anthropometric Traits (GIANT) consortium. They identified 14 known obesity susceptibility loci and 18 new loci associated with BMI at the genome-wide significance level (P<5 * 10-8). Because the prevalence and severity of obesity vary among ethnic groups, it is worthy to investigate these results in another ethnic population. We examined the BMI association of 19 single-nucleotide polymorphisms (SNPs) out of the 32 in 8842 individuals from the Korean Association Resource data, and found 12 SNPs to be associated with BMI in the Korean population. Eight loci, rs10968576 (BDNF), rs3817334 (MTCH2), rs1558902 (FTO), rs571312 (MC4R), rs543874 (SEC16B), rs987237 (TFAP2B), rs2867125 (TMEM18) and rs7138803 (FAIM2), were previously known obesity susceptibility loci, and the remaining four loci, rs1514175 (TNNI3K), rs206936 (NUDT3), rs4771122 (MTIF3) and rs2241423 (MAP2K5), were newly identified as BMI loci by the GIANT study. Further, all 12 SNPs showed the same direction of effect on BMI between the two ethnic groups, suggesting a similar genetic architecture governing the obesity. PMID- 22041984 TI - Sensitization of food reinforcement is related to weight status and baseline food reinforcement. AB - BACKGROUND: Food reinforcement is an empirical index of motivation to obtain food. Higher levels of food reinforcement are associated with increased energy intake and increased body weight. Food reinforcement can vary over repeated food presentations, as people may show reduced reinforcing value if they satiate to repeated reinforcers, or they may show sensitization, or an increase in reinforcing value with repeated presentations. Over the past few years, our laboratory has been studying the impact of repeated administration of large portions of high energy density snack foods on food reinforcement. We have shown in three separate studies that the majority of non-obese individuals become satiated after 2 weeks of the same snack food administration, but that a subset of obese individuals sensitize after this same manipulation. OBJECTIVE: The purpose of the study presented here was to identify predictors of reinforcer satiation or sensitization. SUBJECTS: For the analyses presented here, we combined data sets from three previous studies for a total of 67 adult participants. RESULTS: We found that higher body mass index (BMI) and higher baseline motivation to eat predicted sensitization, and baseline motivation to eat moderated the effects of BMI, such that higher baseline responding for food predicted sensitization in obese individuals, but satiation in non-obese individuals. CONCLUSIONS: These data suggest that repeated exposure to high energy density snack foods may result in sensitization to those foods, with similar effects as drugs of abuse in susceptible individuals, and that an individual's BMI and baseline responding act as predictors of this response. PMID- 22041985 TI - Childhood obesity and risk of the adult metabolic syndrome: a systematic review. AB - BACKGROUND: While many studies have demonstrated positive associations between childhood obesity and adult metabolic risk, important questions remain as to the nature of the relationship. In particular, it is unclear whether the associations reflect the tracking of body mass index (BMI) from childhood to adulthood or an independent level of risk. This systematic review aimed to investigate the relationship between childhood obesity and a range of metabolic risk factors during adult life. OBJECTIVE: To perform an unbiased systematic review to investigate the association between childhood BMI and risk of developing components of metabolic disease in adulthood, and whether the associations observed are independent of adult BMI. DESIGN: Electronic databases were searched from inception until July 2010 for studies investigating the association between childhood BMI and adult metabolic risk. Two investigators independently reviewed studies for eligibility according to the inclusion/exclusion criteria, extracted the data and assessed study quality using the Newcastle-Ottawa Scale. RESULTS: The search process identified 11 articles that fulfilled the inclusion and exclusion criteria. Although several identified weak positive associations between childhood BMI and adult total cholesterol, low-density lipo protein cholesterol, triglyceride and insulin concentrations, these associations were ameliorated or inversed when adjusted for adult BMI or body fatness. Of the four papers that considered metabolic syndrome as an end point, none showed evidence of an independent association with childhood obesity. CONCLUSIONS: Little evidence was found to support the view that childhood obesity is an independent risk factor for adult blood lipid status, insulin levels, metabolic syndrome or type 2 diabetes. The majority of studies failed to adjust for adult BMI and therefore the associations observed may reflect the tracking of BMI across the lifespan. Interestingly, where adult BMI was adjusted for, the data showed a weak negative association between childhood BMI and metabolic variables, with those at the lower end of the BMI range in childhood, but obese during adulthood at particular risk. PMID- 22041986 TI - The identification of two subgroups of obese women with differing endometrial proliferation levels: potential consequences in the development of endometrial cancer. AB - Enhanced endometrial proliferation correlates obesity to type-I (estrogen dependent) endometrial cancer (EC). Our aim was to distinguish obese women (without EC) with differing endometrial proliferation. Endometrial and blood samples were obtained from normal-weight and obese women without EC. Type-I EC samples were obtained from obese patients. On measuring endometrial proliferation (Ki67 and phosphorylated histone H3 (p-H3)), two groups of obese women without EC were identified: obese(High Proliferating) (O(HP)) and obese(Low Proliferating) (O(LP)). Increased Ki67 (88.5%, P<0.001), p-H3 (62.6%, P<0.01), 17beta estradiol/progesterone ratio (46.3%, P<0.01) and endometrial estrogen receptor alpha (ERalpha) (82.2%, P<0.001) were observed in O(HP) compared with O(LP) patients. ECs possessed similar ERalpha and enhanced proliferation as O(HP), suggesting that O(HP) women are at higher risk of type-I EC. O(LP) women were indistinguishable from normal-weight women regarding these determinants of endometrial proliferation, ERalpha and 17beta-estradiol/progesterone ratio. Our data may further define the obesity phenotype in regards to type-I EC risk and may help identify obese women more susceptible to develop type-I EC, allowing early intervention and a potential reduction in mortality. PMID- 22041987 TI - Usefulness of linezolid in the treatment of hospital-acquired pneumonia caused by MRSA: a prospective observational study. AB - Clinical results for linezolid (LZD) treatment of hospital-acquired pneumonia (HAP) caused by methicillin-resistant Staphylococcus aureus (MRSA), particularly microbiologically evaluable or severe cases, are limited in Japan. A prospective observational study was conducted in order to assess the usefulness of LZD in Japanese patients with MRSA pneumonia. The study tracked fifteen participants treated with LZD for pneumonia who met the criteria of the HAP guidelines and were confirmed to have pneumonia caused by MRSA. Of these, six were severe and 13 had received antibiotic treatment before treatment with LZD. Of the 13 participants assessed for their clinical responses, seven were rated as cures, three were rated as failures, and three were indeterminate. The overall cure rate (cure/cure + failure) was 70.0% (7/10), and the cure rate by severity was 33.3% (1/3) for severe cases and 85.5% (6/7) for moderate cases. The one severe case with a clinical response rating of cure had failed to respond to vancomycin. Among the seven participants with a clinical response rating of cure, the microbiological response was eradication in three, presumed eradication in three, and indeterminate in one. Three serious adverse events occurred in two of the 15 participants, but none were considered to be causally related to LZD. The results suggest that LZD has high potential for severe and multidrug-resistant cases. A higher cure rate was achieved in moderate cases. In cases of pneumonia that are most likely MRSA infections with poor prognosis, it was suggested to be important for patient outcome to implement the most effective therapy before the patient's condition becomes serious. PMID- 22041988 TI - Apoptosis of bladder cancer by sodium butyrate and cisplatin. AB - The effects of sodium butyrate (SB), a histone deacetylase inhibitor, in combination with cisplatin (CDDP), for inhibition of cell growth and induction of apoptosis were investigated in bladder cancer cell lines in vitro. Bladder cancer cell lines T24, 253J, and UMUC3 were treated with different concentrations of CDDP or SB. Cell proliferation was studied by XTT assay. Cell-cycle analysis and induction of apoptosis were analyzed by laser scanning cytometry (LSC). Western blot analysis was used to determine expression of p21, p27, TRADD, FADD, caspase 2, and caspase-7. We observed that SB in combination with CDDP induced significant inhibition of cell growth in a dose-dependent manner through G1 arrest and apoptosis, as determined by LSC. When bladder cancer cell lines were treated with SB plus CDDP, Western blotting showed increased expression of p21 but not p27 in T24 cells, whereas both p21 and p27 increased in 253J and UMUC3 cells. All cell lines exhibited a moderate increase in TRADD and decrease in procaspase-2 but no significant change in FADD and procaspase-7. The results showed the synergistic anticancer effect of SB in combination with CDDP, their potential for treatment of bladder cancer, and their mechanism of action in terms of cell signal transduction and induction of apoptosis. PMID- 22041989 TI - Influence of abiotic stress signals on secondary metabolites in plants. AB - Plant secondary metabolites are unique sources for pharmaceuticals, food additives, flavors, and industrially important biochemicals. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Secondary metabolites play a major role in the adaptation of plants to the environment and in overcoming stress conditions. Environmental factors viz. temperature, humidity, light intensity, the supply of water, minerals, and CO2 influence the growth of a plant and secondary metabolite production. Drought, high salinity, and freezing temperatures are environmental conditions that cause adverse effects on the growth of plants and the productivity of crops. Plant cell culture technologies have been effective tools for both studying and producing plant secondary metabolites under in vitro conditions and for plant improvement. This brief review summarizes the influence of different abiotic factors include salt, drought, light, heavy metals, frost etc. on secondary metabolites in plants. The focus of the present review is the influence of abiotic factors on secondary metabolite production and some of important plant pharmaceuticals. Also, we describe the results of in vitro cultures and production of some important secondary metabolites obtained in our laboratory. PMID- 22041990 TI - Delay of flower senescence and abscission in Arabidopsis transformed with an FOREVER YOUNG FLOWER homolog from Oncidium orchid. AB - The ectopic expression of FOREVER YOUNG FLOWER (FYF), a MADS box gene in Arabidopsis, caused significant delay of senescence and a deficiency of abscission in flowers of transgenic Arabidopsis. It was proposed that the function of the FYF gene was related to the regulation of senescence and abscission. This hypothesis was further supported by one line of evidence reported in this study. The evidence is the similar delay of flower senescence and abscission observed in transgenic Arabidopsis ectopically expressing OnFYF, an FYF homolog from the Oncidium orchid, a monocot. This data suggested that the function of FYF homologs in regulating flower senescence and abscission was highly conserved in both dicot and monocot plants. PMID- 22041991 TI - High throughput chemical screening supports the involvement of Ca2+ in cyclic nucleotide-gated ion channel-mediated programmed cell death in Arabidopsis. AB - Recently, we reported the role of Arabidopsis cyclic nucleotide-gated ion channel (AtCNGC) 11 and 12 in Ca2+-dependent physiological responses. AtCNGC11 and 12 have been reported to be involved in plant immunity, but whether these channels play additional physiological roles was not clear before. Using single and double knockout mutants, we have found that these channels play significant roles in Ca2+ signaling, which mediates several physiological processes, such as gravitropic bending and senescence. Here, we conducted a high throughput, non biased chemical screen using the gain-of-function mutant of AtCNGC11 and 12, cpr22. Our data presented here indicates that Ca2+ but not K+ channel blockers suppress AtCNGC11/12-induced lethality. Our data further suggest that AtCNGC11 and 12 are involved in Ca2+-dependent, but not K+-dependent physiological responses in planta. PMID- 22041992 TI - Chemical amination of graphene oxides and their extraordinary properties in the detection of lead ions. AB - A strategy for the ultra-sensitive detection of Pb(2+) in aqueous media has been developed. The combination of oxidative exfoliation of graphite and subsequent chemical amination resulted in an amine functionalized graphene oxide, which showed ultra-high sensitivity in detecting Pb(2+), as it is an active material in modified anodic stripping voltammetry. A detection limit of as low as 10(-13) M (0.1 pM) has been reached, which is comparable to the result obtained from atomic absorption spectrometry, but is dramatically lower than that from other reported electrochemical analysis methods. This simple and economic approach opens up a new window for the portable, quick, and ultra-sensitive detection of lead ions. PMID- 22041993 TI - Re: efficiency of percutaneous nephrolithotomy in pediatric patients using adult type instruments. PMID- 22041994 TI - Percutaneous nephrolithotomy: keeping the bridge for one night. AB - This study was conducted to compare nephrostomy-free percutaneous nephrolithotomy (PCNL) with early nephrostomy tube removal (after 1 day). A prospective study started from January 2008 through December 2009 and included patients who underwent non-complicated PCNL through a single tract without intra-operative residual stones. Nephrostomy-free technique was performed during 2008 (nephrostomy-free group). During 2009, a nephrostomy tube was placed for 1 day (1 day nephrostomy group). Both groups were compared for post-operative events, dose of analgesia, hemoglobin deficit and hospital stay. The study included 55 patients (27 in nephrostomy-free group and 28 in 1-day nephrostomy group). There were no statistically significant differences between patients, renal and stone characteristics of both groups. Post-operative events were significantly more in nephrostomy-free group (26 vs. 14.3%, p = 0.039). They include hematuria in three (11.1%) of nephrostomy-free patients and one (3.6%) of 1-day nephrostomy patient, severe renal colic in four patients of nephrostomy-free group (14.8%), and temporary urinary leakage via the nephrostomy site in three patients of 1-day nephrostomy group (10.7%). Mean dose of post-operative analgesia, mean hemoglobin deficit and hospital days were comparable for both groups (p = 0.946, 0.541, 0.807, respectively). A second look PCNL was performed through the already present tract to retrieve residual stones in two patients with nephrostomy. In conclusion, 1-day nephrostomy technique after PCNL showed significantly better post-operative course. It was comparable to nephrostomy-free technique in analgesic requirements and hospital stay. The nephrostomy tube provided a bridge for second look nephroscopy. PMID- 22041995 TI - The Munich outbreak of cutaneous cowpox infection: transmission by infected pet rats. AB - Cowpox virus infection of humans is an uncommon, potentially fatal, skin disease. It is largely confined to Europe, but is not found in Eire, or in the USA, Australasia, or the Middle or Far East. Patients having contact with infected cows, cats, or small rodents sporadically contract the disease from these animals. We report here clinical aspects of 8 patients from the Munich area who had purchased infected pet rats from a local supplier. Pet rats are a novel potential source of local outbreaks. The morphologically distinctive skin lesions are mostly restricted to the patients' necks, reflecting the infected animals' contact pattern. Individual lesions vaguely resemble orf or Milker's nodule, but show marked surrounding erythema, firm induration and local adenopathy. Older lesions develop eschar, leaving slow-healing, deep ulcerative defects after eschar separation. Severe flu-like illness may be present in the acute phase. Smallpox-vaccinated patients tend to develop less severe reactions and heal more quickly. The differential diagnosis may include other localized orthopoxvirus infections, herpes simplex, bacterial infection, anthrax, foreign body granuloma, and primary tuberculosis. Dermatologists should be aware of the diagnostic and therapeutic algorithms for handling this disease. PMID- 22041996 TI - Primary care health workforce in the United States. AB - As a result of the Patient Protection and Affordable Care Act, more than 30 million people are expected to be newly insured, many of whom will be seeking a source for primary care. At the same time, media reports and some studies are proclaiming a current or imminent shortage of primary care providers. This Synthesis examines the evidence on the primary care workforce including: the supply and distribution of the workforce; the historical and projected demand on the primary care workforce; the effects of payment policies and scope of practice laws on the workforce; and how the primary care workforce is evolving. PMID- 22041997 TI - Colonization and community structure of root-associated microorganisms of Sabina vulgaris with soil depth in a semiarid desert ecosystem with shallow groundwater. AB - Arbuscular mycorrhizal fungi (AMF) have been observed in deep soil layers in arid lands. However, change in AMF community structure with soil depth and vertical distributions of the other root-associated microorganisms are unclear. Here, we examined colonization by AMF and dark septate fungi (DSF), as well as the community structure of AMF and endophytic fungi (EF) and endophytic bacteria (EB) in association with soil depth in a semiarid desert with shallow groundwater. Roots of Sabina vulgaris and soils were collected from surface to groundwater level at 20-cm intervals. Soil chemistry (water content, total N, and available P) and colonization of AMF and DSF were measured. Community structures of AMF, EF, and EB were examined by terminal restriction fragment length polymorphism analysis. AMF colonization decreased with soil depth, although it was mostly higher than 50%. Number of AMF phylotypes decreased with soil depth, but more than five phylotypes were observed at depths up to 100 cm. Number of AMF phylotypes had a significant and positive relationship with soil moisture level within 0-15% of soil water content. DSF colonization was high but limited to soil surface. Number of phylotypes of EF and EB were diverse even in deep soil layers, and the community composition was associated with the colonization and community composition of AMF. This study indicates that AMF species richness in roots decreases but is maintained in deep soil layers in semiarid regions, and change in AMF colonization and community structure associates with community structure of the other root-associated microorganisms. PMID- 22041998 TI - Cereal fiber and coronary heart disease: a comparison of modeling approaches for repeated dietary measurements, intermediate outcomes, and long follow-up. AB - The appropriate manner of incorporating incident angina, coronary artery bypass surgery (CABG), percutaneous coronary intervention (PCI), diabetes, hypertension, and hypercholesterolemia, which may be both intermediate events and time dependent confounders, into analyses of diet and coronary heart disease (CHD) is not clear. Using data from 72,266 women in the Nurses' Health Study between 1984 and 2006, the authors examined the relation between report of intermediate events and change in cereal fiber intake and used different proportional hazards models to evaluate the association between cereal fiber and CHD. Cereal fiber intake increased significantly among participants who reported hypercholesterolemia (0.42 g/day; 95% CI: 0.34, 0.51 g/day) and diabetes (0.07 g/day with each additional 2-year increment; 95% CI: 0.01, 0.13 g/day). However, angina, CABG/PCI, and hypertension were not associated with a change in cereal fiber intake and thus were not important time-dependent confounders. Cereal fiber intake was inversely associated with risk of CHD in all proportional hazards models, but results varied modestly depending on the approach used to incorporate multiple measures of diet. Because stopping the updating of dietary variables when an intermediate event is diagnosed may lead to misclassification, future analyses should consider updating diet even after these diagnoses to best represent long-term intake. To best evaluate associations with incidence of disease, considerations should include the temporal trends in diet, changes in intake following intermediate events, and latency patterns. Sensitivity analyses can also be useful. PMID- 22041999 TI - Case fatality of acute myocardial infarction: an emerging gender gap. AB - There has been a cardiovascular revolution since the 1970s in many industrialized countries with rapidly declining mortality rates especially for coronary heart disease (CHD). This has been most striking for men. A slower decline in out-of hospital mortality for women below 55 has been demonstrated in Finland. This, and indications of increasing incidence of CHD in the younger segments of the female populations may be pointing at a shift in the incidence and mortality pattern of this disorder. These findings should be taken seriously, reminding us that younger women are not protected against coronary heart disease. PMID- 22042000 TI - Superposition-additive approach: thermodynamic parameters of clusterization of monosubstituted alkanes at the air/water interface. AB - The applicability of the superposition-additive approach for the calculation of the thermodynamic parameters of formation and atomization of conjugate systems, their dipole electric polarisabilities, molecular diamagnetic susceptibilities, pi-electron circular currents, as well as for the estimation of the thermodynamic parameters of substituted alkanes, was demonstrated earlier. Now the applicability of the superposition-additive approach for the description of clusterization of fatty alcohols, thioalcohols, amines, carboxylic acids at the air/water interface is studied. Two superposition-additive schemes are used that ensure the maximum superimposition of the graphs of the considered molecular structures including the intermolecular CH-HC interactions within the clusters. The thermodynamic parameters of clusterization are calculated for dimers, trimers and tetramers. The calculations are based on the values of enthalpy, entropy and Gibbs' energy of clusterization calculated earlier using the semiempirical quantum chemical PM3 method. It is shown that the proposed approach is capable of the reproduction with sufficiently enough accuracy of the values calculated previously. PMID- 22042003 TI - Lipid bilayer assembly at a gold nanocavity array. AB - The assembly of lipid bilayer membranes, using ultrasonic disruption of liposomes of L-alpha-Dimyristoyl phosphatidylcholine, across 820 nm diameter spherical cap gold cavity arrays is demonstrated. PMID- 22042002 TI - Walnut allergy in peanut-allergic patients: significance of sequential epitopes of walnut homologous to linear epitopes of Ara h 1, 2 and 3 in relation to clinical reactivity. AB - BACKGROUND: Peanut allergy is a frequent and potentially life-threatening food allergy. Despite the large taxonomic distance between the plants, peanut-allergic patients often react to tree nuts such as walnuts. While the allergens of peanut and walnut have a high degree of homology in their amino-acid sequences, it is unknown whether this similarity is responsible for the observed co-reactivity. Therefore, we analyzed the binding of specific IgE antibodies to sequential epitopes of peanut and walnut in peanut-allergic patients with and without walnut allergy. METHODS: The IgE binding to previously described sequential epitopes of peanut and the homologous regions of walnut was assessed in 32 peanut-allergic patients using a peptide microarray technology. Twelve patients had a clinically relevant walnut allergy and 20 were tolerant to walnut. Inhibition assays with peanut peptides and corresponding walnut sequences were performed to show specific binding to sequential epitopes. RESULTS: No differences in the recognition of sequential epitopes could be found between peanut-allergic patients with or without walnut allergy. Only a few patients showed IgE binding to walnut sequences that corresponded to sequential epitopes of peanut. In the inhibition assays, no relevant cross-reacting IgE antibodies could be detected for the peptides analyzed. CONCLUSION: Our results indicate that although they share a rather high degree of homology with the corresponding regions of walnut allergens, the sequence stretches previously identified as sequential IgE binding epitopes of Ara h 1, Ara h 2 and Ara h 3 have no IgE binding equivalents in walnut allergens. PMID- 22042001 TI - Role of p53 in neurodegenerative diseases. AB - BACKGROUND: p53 plays an important role in many areas of cellular physiology and biology, ranging from cellular development and differentiation to cell cycle arrest and apoptosis. Many of its functions are attributed to its role in assuring proper cellular division. However, since the establishment of its role in cell cycle arrest, damage repair, and apoptosis (thus also establishing its importance in cancer development), numerous reports have demonstrated additional functions of p53 in various cells. In particular, p53 appears to have important functions as it relates to neurodegeneration and synaptic plasticity. OBJECTIVE: In this review, we will address p53 functions as it relates to various neurodegenerative diseases, mainly its implications in the development of HIV associated neurocognitive disorders. CONCLUSION: p53 plays a pivotal role in the development of neurodegenerative diseases through its interaction with cellular factors, viral factors, and/or small RNAs that have the ability to promote the development of these diseases. Hence, inhibition of p53 may present an ideal target to restore neuronal functions. PMID- 22042004 TI - Independent regulation of Na+ and K+ balance by the kidney. AB - The understanding of the independent regulation of sodium and potassium by the kidney has remained elusive. Recent evidence now points to dissimilar regulatory mechanisms in ion handling, dependent on the presence of either aldosterone alone or angiotensin II with aldosterone among other factors. This review summarizes past and present information in an attempt to reconcile the current concepts of differential regulation of sodium and potassium balance through the with-no lysine (K) kinase (WNK) system and the previous knowledge regarding ion transport mechanisms in the distal nephron. PMID- 22042005 TI - Estrogen modulates abdominal adiposity and protects female mice from obesity and impaired glucose tolerance. AB - PURPOSE: Obesity increases the risk of diabetes. The dysregulation of estrogen metabolism has been associated with the susceptibility to obesity and diabetes. Here, we explore the role estrogen plays in sex differences in obesity and glucose metabolism, specifically adipocyte biology. METHODS: We randomized C57BL/6 J male, non-ovariectomized female, ovariectomized female, and ovariectomized female mice supplemented with 17beta estradiol to receive a calorie-restricted, low- or a high-fat diet (15 mice per group). We measured weight gained, calories consumed, percent body fat, abdominal adipose tissue, adipocyte size, lipogenic and adipogenic gene expression, and glucose tolerance. RESULTS: Male mice had a higher susceptibility to obesity than intact female mice. However, removal of the ovaries in female mice eliminated the protection to obesity and estrogen supplementation restored this protection. Male and ovariectomized female mice gained weight predominately in the form of abdominal adipose tissue possibly due to an increase in adipocyte size. Moreover, for mice consuming the high-fat diet, male and ovariectomized female mice had significantly higher levels of leptin mRNA and lower hormone-sensitive lipase mRNA relative to intact female mice and ovariectomized female mice supplemented with estrogen. Additionally, estrogen had a strong inhibitory effect on key adipogenic genes in non-ovariectomized female and ovx-female mice supplemented with estrogen. Finally, we show that male and ovariectomized female mice consuming the high-fat diet had a higher incidence of glucose intolerance. CONCLUSION: Estrogen protects female mice from obesity and impaired glucose tolerance possibly by modulating the expression of genes regulating adipogenesis, lipogenesis, and lipolysis. PMID- 22042006 TI - Influence of bread crust-derived Maillard reaction products on phosphorus balance in rats. AB - BACKGROUND: Maillard reaction products (MRP) improve food palatability and are linked to some positive biological actions. However, diverse negative consequences, some related to protein damage and mineral availability, have been established. AIM OF STUDY: We investigated the effects of MRP, from a bread crust diet, on phosphorus bioavailability and tissue distribution in rats to determine whether these effects are related to the molecular weight of browning products. METHODS: During a study period of 88 days, rats were fed either a control diet or one of the following: with bread crust as a source of MRP, or one with its soluble high molecular weight, soluble low molecular weight or insoluble fraction (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a phosphorus balance was performed, after which the animals were sacrificed and some organs removed to analyse phosphorus content. A second balance was carried out throughout the experimental period to calculate phosphorus retention. RESULTS: Phosphorus balance in the last week was unchanged. However, considering the whole experimental period, a trend towards improved bioavailability, significant in the HMW group, was observed. Higher phosphorus concentrations were measured in the small intestine and bone. CONCLUSIONS: The consumption of MRP derived from bread did not alter phosphorus retention, due to increased bioavailability, especially concerning HMW compounds. The overall phosphorus body content remained unchanged and there were no changes in the bone, its principal metabolic destination. However, MRP consumption markedly raised phosphorus levels at the digestive level, especially when consumed as isolate fractions. The slower rate of stomach emptying is assumed to be related to this effect. PMID- 22042009 TI - Diagnosis of uveal melanoma. AB - The diagnosis of uveal melanoma is based on clinical examination with the slit lamp and indirect ophthalmoscope together with ultrasonography of the eye. Large to medium-sized melanomas are reliably diagnosed using these methods. The challenge lies in early detection. Small melanomas are more difficult to tell from presumed naevi. A useful mnemonic 'to find small ocular melanomas' reminds the general ophthalmologist to look for tumour thickness of more than 2 mm, subretinal fluid, visual symptoms, orange pigment and location of the tumour margin at the optic disc. Optical coherence tomography and fundus autofluorescence imaging help in identifying subretinal fluid and orange pigment and in measuring the thickness of thin choroidal tumours. Each of the risk characteristics roughly doubles the likelihood of growth so that the risk for growth is about 30 times higher when all five characteristics are present as compared to their absence. In addition, a low acoustic profile, the absence of a halo around the tumour and the absence of drusen over it increase the likelihood of growth. Patients with a choroidal melanocytic tumour with at least one risk characteristic benefit from referral to an ocular oncologist. We recommend that the rest of the patients be made aware of their presumed naevus and that they should be observed periodically. The patients should also be told to return immediately if they develop new visual symptoms. Finally, the trend is toward taking a biopsy of suspicious small choroidal tumours as an alternative to documenting growth before treating them as melanomas. PMID- 22042007 TI - Procyanidin B2 induces Nrf2 translocation and glutathione S-transferase P1 expression via ERKs and p38-MAPK pathways and protect human colonic cells against oxidative stress. AB - PURPOSE: Procyanidin B2 (PB2) is a naturally occurring flavonoid widely found in cocoa, red wine and grape juice. Recent studies have suggested that PB2 could protect against oxidative stress- and chemical-induced injury in colonic cells by modulating the endogenous cellular defence. However, the precise mechanism for this protection is not fully understood. Herein, we examined the effect of PB2 on the expression of one of the major antioxidant/detoxificant enzymes related to intestinal protection, the glutathione S-transferase P1 (GSTP1), and the molecular mechanisms involved. METHODS: Human colonic Caco-2 cells were treated with PB2 at different times and enzymatic activity, and mRNA and protein levels of GSTP1 were evaluated. The nuclear translocation of the transcription factor NF erythroid 2-related factor (Nrf2) and the phosphorylation states of specific proteins central to intracellular signalling cascades were also investigated. RESULTS: PB2 induced the expression and activity of GSTP1 and the nuclear translocation of Nrf2. Interestingly, two important signalling proteins involved in Nrf2 translocation, the extracellular signal-regulated protein kinases (ERKs) and the p38 mitogen-activated protein kinase (MAPK) were also activated. Further experiments with specific inhibitors of both pathways confirmed their critical role in the beneficial effects induced by PB2. CONCLUSIONS: The present results show that PB2 protects against oxidative injury in colonic cells and up-regulate the expression of GSTP1 via a mechanism that involves ERK and p38 MAPK activation and Nrf2 translocation. These results provide a molecular basis for the potential contribution of PB2 in the prevention of oxidative stress-related intestinal injury and gut pathologies. PMID- 22042010 TI - Treatment selection for uveal melanoma. AB - Uveal melanomas can be treated by various forms and combinations of radiotherapy, phototherapy and local resection, which need to be tailored to the tumour size, location and extent as well as the patient's needs, fears and wishes. Many factors complicate the process of treatment selection and these include limited resources, incomplete knowledge of the patient's condition (e.g. genetic tumour type) and inadequate scientific evidence on which to base decision making. In this chapter, I describe how I select treatment for small, large, juxtapapillary, ciliary and iridal melanomas, respectively, and for melanocytic tumours of indeterminate malignancy. I also describe how I interact with patients so as to select the most suitable treatment in a personalised manner. Finally, I discuss challenges and shortcomings in this aspect of patient care, also providing suggestions for further research in this field. PMID- 22042011 TI - Ruthenium-106 brachytherapy. AB - Brachytherapy is the most common method for treating uveal melanoma, and currently the ruthenium-106 (Ru-106) and iodine-125 (I-125) applicators are the most frequently used. Ru-106 applicators were introduced by Prof. Peter Lommatzsch in the 1960s, and since then have been used widely by many ocular oncologists, mainly in Europe. The Ru-106 isotope is a beta ray (electron) emitter, and as such it has a limited depth of penetration. This is the reason why many experts use Ru-106 applicators for tumors with a maximal thickness of up to 7.0 mm, although others use it successfully for thicker tumors. The Ru-106 applicators are manufactured commercially and have a half-life of about 1 year. Ru-106 brachytherapy for uveal melanoma provides excellent local control rates and eye preservation with a relatively low recurrence rate. The main advantage of Ru-106 over other isotopes is the better preservation of vision in the treated eye, and less damage to the healthy parts of the eye due to its limited range of radiation. This can also be achieved by positioning the Ru-106 plaque eccentrically, away from the macula and optic nerve head. Ru-106 brachytherapy can be used in combination with other methods of treatment of uveal melanoma, such as local resection or transpupillary thermotherapy, and is sporadically combined with other isotopes, such as gamma-emitting cobalt-60 and I-125. PMID- 22042012 TI - Treatment of uveal melanoma by accelerated proton beam. AB - Proton beam irradiation of uveal melanoma has great advantages compared to brachytherapy because of the homogenous dose delivered to the tumor and the possibility of sparing normal tissue close to the tumor. We describe the technique of proton beam therapy including the surgical technique of clip positioning, the radiotherapy delivery technique and the dose administered (60 Gy cobalt relative biological effectiveness in 4 fractions). Indications of proton beam are given and the follow-up procedure is described. An inactive residual tumor scar is observed after 2-3 years. Results are given comparing the most recent series of patients treated at the Institut Curie-Orsay proton therapy center with the data published in the literature. The metastasis rate at 10 years varies between 25 and 30%. Local control is excellent. The local recurrence rate at 10 years is usually around 5%. Secondary enucleation is performed in 10-15% of patients either due to complications or local recurrence. Complications such as retinal detachment, maculopathy, papillopathy, cataract, glaucoma, vitreous hemorrhage and dryness are described. The severest complication that usually leads to secondary enucleation is neovascular glaucoma and it is encountered after irradiation of large to extra-large tumors. The toxic tumor syndrome has recently been described. It is hypothesized that the residual tumor scar may produce proinflammatory cytokines and VEGF leading to intraocular inflammation and neovascular glaucoma. Additional treatments after proton beam such as transpupillary thermotherapy, endoresection of the tumor scar or intravitreal injections of anti-VEGF may reduce the rate of these complications. PMID- 22042013 TI - Stereotactic photon beam irradiation of uveal melanoma. AB - Stereotactic photon beam irradiation has been under clinical investigation for the treatment of uveal melanoma for over 15 years. Single-fraction stereotactic radiosurgery (SRS) is usually done with a gamma knife as well as more recently with a cyberknife. The therapeutic single dose has been reduced to as low as 35 Gy over the past few years without reduction in tumor control. Doses of 40 Gy delivered at the 50% isodose result in good local tumor control and acceptable toxicity. Since radiobiological studies indicate a possible advantage of hypofractionated treatment over a single very large fraction to sterilize uveal melanoma cell lines, fractionated stereotactic radiotherapy (SRT)has gained additional interest. Besides increased tumor control, toxicity should theoretically be reduced by fractionation. Linear accelerators (LINAC) have the advantage of a feasible fractionation. Most LINAC studies employ a hypofractionated scheme of 4-5 fractions and total doses between 50 and 70 Gy. The efficacy of SRT for uveal melanoma has been proven in different studies with local tumor control rates reported over 90%, 5 and 10 years after treatment. Radiogenic side effects after SRT are reported similarly to other forms of radiotherapy, with cataract development, radiation retinopathy, opticopathy and neovascular glaucoma being responsible for the majority of secondary vision losses and secondary enucleations. Overall, stereotactic photon beam radiotherapies (SRS and SRT) are considered effective treatment modalities for uveal melanoma, with promising late tumor control and toxicity rates. Additional studies and longer follow-up are indicated to finally confirm optimal treatment modalities. PMID- 22042014 TI - Local resection of uveal melanoma. AB - Local resection of uveal melanoma is aimed at conserving the eye and useful vision while removing any threat of metastatic spread. The tumour can be removed en bloc through a scleral opening (i.e., 'exoresection') or in a piecemeal fashion with a vitreous cutter passed through the retina (i.e., 'endoresection'). Variations of exoresection include iridectomy, iridocyclectomy, cyclochoroidectomy, and choroidectomy. Endoresection can be performed through a retinotomy or under a large retinal flap. Both exoresection and endoresection can be undertaken as a primary procedure, or after other conservative therapy as treatment for recurrent or toxic tumour. Each can be performed in combination with some form of radiotherapy, which can precede or follow the surgical resection. Endoresection should be relatively straightforward for experienced vitreoretinal surgeons; however, exoresection is more challenging, particularly with large and posterior tumours, because of the need for hypotensive anaesthesia and other measures to control intra-operative haemorrhage. In addition to their technical complexities, exoresection and endoresection are limited by intuitive concerns regarding iatrogenic tumour dissemination. When these obstacles are overcome, local resection preserves eyes that would otherwise be inoperable and produces relatively large tumour samples, which are useful for prognostication and research and which may one day have therapeutic value. PMID- 22042015 TI - Biopsies in uveal melanoma. AB - The ability to obtain the proper clinical diagnosis in cases of suspected intraocular tumors has greatly advanced during the past 50 years. The clinical characteristics of most intraocular tumors (size, shape, color, and texture) are detectable by skilled ophthalmoscopic examination and, with the use of adjunctive techniques (mainly ultrasonography), the proper diagnosis can be reached without invasive procedures. Notwithstanding, some intraocular tumors need to be biopsied to obtain a reliable diagnosis. In the cytogenetic era, intraocular tumor management is changing, and tumor-sampling procedures are becoming the main prognostic (and theoretically also diagnostic) tools for uveal melanoma. In spite of the widespread use of biopsies in general surgical practice, in ophthalmic oncology, indications and contraindications for biopsy continue to be under debate. The purpose of this paper is to critically evaluate the role of uveal melanoma biopsy in current clinical practice. PMID- 22042016 TI - Analysis of intraocular biopsies. AB - In this chapter, the importance of intraocular biopsies in the diagnosis/exclusion of ocular malignancies and prognostication is outlined. Despite improvements in ancillary studies in ophthalmology, intraocular biopsies are increasingly being performed in many ocular oncology centres. Experience is required in taking these biopsies, in their transport to the pathology laboratory, in their triaging and processing, and in their interpretation. To optimize the biopsy yield, well-tested and practical standard operational procedures for morphological, immunocytological and molecular genetic analyses are necessary. 'Tips and tricks' for the fixation and processing of intraocular tissue and fluid biopsies are provided. For example, a fixative such as Cytolyt or HOPE fixation is recommended for vitreous biopsies, allowing for all investigations to be performed, including DNA-based molecular genetic techniques, such as polymerase chain reaction used in clonality analysis in lymphoma diagnosis and in organism identification in endophthalmitis. Most solid tissue samples can be placed in buffered formalin, with the exception of those requiring RNA-based molecular techniques, here fresh tissue being preferable. The importance of incorporating data from all investigations and summarizing them as an integrated report is emphasized. The pitfalls of using any single test (e.g. a molecular genetic test) as a 'stand-alone' investigation are highlighted. Communication with relevant clinical information between surgeon and pathologist is essential at each stage: for sample delivery, for exclusion of differential diagnoses and for rapid result transmission. The current molecular genetic techniques for uveal melanoma prognostication are summarized, and how their data can be used for instigation of individualized management plans for patients discussed. PMID- 22042017 TI - Anti-angiogenic therapy in uveal melanoma. AB - For several decades, targeting of tumor-related vessels has been regarded as a potential anticancer therapy. Such anti-angiogenic therapy is based on the assumption that a tumor cannot grow beyond the limits of diffusion (about 1-2 mm) of oxygen and nutrients from capillaries, unless angiogenesis takes place. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, regulating vasopermeability as well as the proliferation and migration of endothelial cells. In several types of cancer (colon carcinoma, soft tissue sarcomas and gastric cancer), serum VEGF levels are a marker for disease stage and an indicator of metastasis. VEGF levels are significantly elevated in uveal melanoma patients with metastatic disease compared to patients without metastases. Anti-angiogenic therapy, such as bevacizumab, is currently used for the treatment of metastases of several malignancies. Anti-angiogenic therapy has not yet been tested for the treatment of primary uveal melanoma or related metastatic disease. Clinicians, however, have a broad experience with anti angiogenic agents in patients with uveal melanoma by treating the complications of radiation therapy. We will discuss tumor angiogenic processes and related molecular pathways in uveal melanoma. The role of VEGF and the potential use of current commercially and experimentally available anti-angiogenic drugs for the treatment of primary uveal melanoma and/or metastatic disease will be explained below. PMID- 22042018 TI - Immunotherapy of uveal melanoma. AB - Uveal melanoma is a malignancy with exceptional features for treatment with immunotherapy. Primary uveal melanoma can be treated with a variety of therapies that may limit the growth of the primary tumor in the eye and partially preserve vision. However, none of these treatment modalities prevents the development of metastases, which predominantly arise in the liver and universally remain fatal. Novel therapies are being explored for their effectiveness against uveal melanoma metastases and immunotherapy may be a potential option as an alternative or adjunctive treatment, even in the prophylactic setting. Uveal melanoma may be particularly responsive to T-cell-based immunotherapy because it originates in the immune-privileged eye. The localization of the primary tumor in the immune privileged eye excuses the tumor cells from continuous immunological pressure. This may render primary uveal melanoma more immunogenic than tumor cells from non privileged sites and allow expression of novel tumor antigens to which the patient's endogenous T cell repertoire is not tolerized. The clinical and genetic differences between cutaneous and uveal melanomas underscore the need for immunotherapy specifically designed for uveal melanoma patients. In this review, the current developments in the field of immunotherapy for uveal melanoma are discussed, with a special emphasis on T-cell-based strategies. PMID- 22042019 TI - Genetic determinants of uveal melanoma. AB - Uveal melanoma (UM) arises from neural crest-derived melanocytes of the choroid and the ciliary body. About 50% of patients develop metastatic disease despite efficient control of the primary tumor. For about 15 years, cytogenetic and, recently, genome-wide analysis techniques have shown that UM can be classified into 2 genomic groups correlating with prognostic clinicopathologic features: class 1 tumors, with a low risk of metastases, typically characterized by a gain of the 6p chromosome arm, often associated with a gain of the distal part of the 8q chromosome arm, and class 2 tumors, with a high metastatic risk, presenting loss of the entire chromosome 3 and gain of the entire 8q, related to the formation of isochromosomes. Genome-wide expression profiling has proved to be a powerful tool for separating these 2 classes. However, despite advances in the genomic and prognostic characterization of UM, the knowledge of pathways deregulated in these tumors is just emerging and, in contrast to cutaneous melanoma, no major predisposing genes are known. Altered or deregulated genes are reviewed in this chapter. Inactivating mutations have recently been identified by exome sequencing in gene BAP1, mapping to 3p21.1, in class 2 tumors. Among other discriminant genes identified from genome-wide expression profiling, PTP4A3, mapping to 8q24.3, coding for a protein promoting cell migration, is highly overexpressed in class 2 tumors. The overall expression signature of class 2 tumors suggests they may originate from neuroectodermal stem cells. PMID- 22042020 TI - Therapeutic options in metastatic uveal melanoma. AB - Systemic treatments for metastatic uveal melanoma patients give poor results. R0 resection of liver metastases showed a real benefit in survival in a very highly selected population. Based on our multivariate analysis, we propose surgical treatment to metastatic patients with time from diagnosis of uveal melanoma to liver metastases > 24 months, number of liver metastases <=4 lesions, and absence of detectable miliary disease. Liver MRI is currently the best imaging method in this context even if miliary disease is still difficult to diagnose. Molecular and chromosomal classification strongly predicting metastatic death has to be used to identify genetic profiles and pathways involved in the pathogenesis of uveal melanoma leading to new targeted therapeutic strategies. PMID- 22042021 TI - Stem cell transplantation strategies for the restoration of cognitive dysfunction caused by cranial radiotherapy. AB - Radiotherapy often provides the only clinical recourse for those afflicted with primary or metastatic brain tumors. While beneficial, cranial irradiation can induce a progressive and debilitating decline in cognition that may, in part, be caused by the depletion of neural stem cells. Given the increased survival of patients diagnosed with brain cancer, quality of life in terms of cognitive health has become an increasing concern, especially in the absence of any satisfactory long-term treatments. To address this serious health concern we have used stem cell replacement as a strategy to combat radiation-induced cognitive decline. Our model utilizes athymic nude rats subjected to cranial irradiation. The ionizing radiation is delivered as either whole brain or as a highly focused beam to the hippocampus via linear accelerator (LINAC) based stereotaxic radiosurgery. Two days following irradiation, human neural stem cells (hNSCs) were stereotaxically transplanted into the hippocampus. Rats were then assessed for changes in cognition, grafted cell survival and for the expression of differentiation-specific markers 1 and 4-months after irradiation. Our cognitive testing paradigms have demonstrated that animals engrafted with hNSCs exhibit significant improvements in cognitive function. Unbiased stereology reveals significant survival (10-40%) of the engrafted cells at 1 and 4-months after transplantation, dependent on the amount and type of cells grafted. Engrafted cells migrate extensively, differentiate along glial and neuronal lineages, and express a range of immature and mature phenotypic markers. Our data demonstrate direct cognitive benefits derived from engrafted human stem cells, suggesting that this procedure may one day afford a promising strategy for the long-term functional restoration of cognition in individuals subjected to cranial radiotherapy. To promote the dissemination of the critical procedures necessary to replicate and extend our studies, we have provided written and visual documentation of several key steps in our experimental plan, with an emphasis on stereotaxic radiosurgey and transplantation. PMID- 22042022 TI - The effects of spirotetramat on life history traits and population growth of Tetranychus urticae (Acari: Tetranychidae). AB - The effects of spirotetramat, a tetramic acid derivative, on gross fertility, net fertility, female longevity and the instantaneous rate of increase of two-spotted spider mite, Tetranychus urticae (Acari: Tetranychidae) were investigated after treatment of female teleiochrysalises (the first assay) and pre-ovipositional females (the second assay). Spirotetramat was applied to the leaf discs by Potter spray tower and the following series of concentrations was applied: 200, 60, 18, 5.4 and 1.62 mg/l. In both assays after 24 h of exposure, surviving females without symptoms of poisoning were used for further procedure. In the first assay, gross fertility of treated females was reduced by 2.4-64.7% and net fertility by 12.4-88.8%, compared to the control. Gross fertility of the females treated with 1.62 and 5.4 mg/l did not significantly differ from the control, whereas all concentrations, except the lowest, significantly reduced net fertility and female longevity. Treatments with 200, 60, and 18 mg/l significantly reduced the instantaneous rate of increase. In the second assay, gross fertility and net fertility were reduced by 43.7-93.3% and 73.8-98.5%, respectively. All concentrations, except the lowest, significantly reduced gross fertility, whereas net fertility and longevity in all treated females were significantly lower compared to the control. All concentrations, except the lowest, significantly reduced the instantaneous rate of increase, provided that concentrations of 200, 60 and 18 mg/l caused population decline. The effects of spirotetramat and its impact on T. urticae management are discussed. PMID- 22042024 TI - The European Renal Best Practice Advisory Board's dialysis initiation guidelines: one size won't fit all. PMID- 22042027 TI - Hypertension in pediatric patients with childhood-onset chronic kidney disease: much to be learned, more to be done. AB - Pediatric patients with chronic kidney disease are increasingly recognized as being at increased risk of developing cardiovascular disease as adults. Numerous risk factors contribute, hypertension being one of the most identifiable and potentially modifiable. Despite this, numerous studies have demonstrated that hypertension is common and is frequently underrecognized and/or undertreated in this population. Greater efforts are needed to identify and effectively treat hypertension in these vulnerable patients to reduce the future burden of adult cardiovascular disease. PMID- 22042028 TI - Fibrinogen as a damage-associated mitogenic signal for the renal fibroblast. AB - Fibroblast proliferation is central to the evolution of renal tubulointerstitial fibrosis. Using both in vivo and in vitro approaches, Sorensen et al. describe a role for fibrinogen as a cell-surface-receptor-mediated mitogen for renal fibroblasts. This interaction, likely to be initiated by injury and extravasation and to signal principally via Toll-like receptors, implicates fibrinogen in renal fibrosis beyond its textbook description as a scaffold precursor at the end of the coagulation cascade. PMID- 22042029 TI - Short-term effects of vitamin D receptor activation on serum creatinine, creatinine generation, and glomerular filtration. AB - Vitamin D receptor activation may have pleiotropic effects in a variety of tissues. Experimental studies with vitamin D receptor activation demonstrate an ability to delay progression of renal disease. In humans, vitamin D receptor activation reduces albuminuria. Yet some clinical studies demonstrate that patients receiving vitamin D supplementation have an elevation in serum creatinine and a decline in estimated glomerular filtration rate. These observations may be explainable by an effect of vitamin D receptor activation on creatinine metabolism. PMID- 22042030 TI - How best to improve survival in hemodialysis patients: solute clearance or volume control? AB - How much dialysis is required for optimal well-being and long-term survival? The Frequent Hemodialysis Network completed two prospective trials examining the effect of more frequent, short hours and, now, of nocturnal hemodialysis compared with standard thrice-weekly treatments. Whereas the short-hours trial reported benefits with more frequent dialysis, somewhat paradoxically, nocturnal hemodialysis had fewer advantages. However, this trial was probably underpowered, and confounded by the beneficial effects of home hemodialysis in the control group. PMID- 22042032 TI - On ANCA-associated glomerulonephritis in the very elderly. PMID- 22042034 TI - The apoptotic program promotes tissue remodeling and fibrosis. PMID- 22042035 TI - Hydrogen sulfide increases after a single hemodialysis session. PMID- 22042036 TI - Brown tumor: still an old disease? PMID- 22042037 TI - Effects of cytokines on potassium channels in renal tubular epithelia. AB - Renal tubular potassium (K(+)) channels play important roles in the formation of cell-negative potential, K(+) recycling, K(+) secretion, and cell volume regulation. In addition to these physiological roles, it was reported that changes in the activity of renal tubular K(+) channels were involved in exacerbation of renal cell injury during ischemia and endotoxemia. Because ischemia and endotoxemia stimulate production of cytokines in immune cells and renal tubular cells, it is possible that cytokines would affect K(+) channel activity. Although the regulatory mechanisms of renal tubular K(+) channels have extensively been studied, little information is available about the effects of cytokines on these K(+) channels. The first report was that tumor necrosis factor acutely stimulated the single channel activity of the 70 pS K(+) channel in the rat thick ascending limb through activation of tyrosine phosphatase. Recently, it was also reported that interferon-gamma (IFN-gamma) and interleukin-1beta (IL 1beta) modulated the activity of the 40 pS K(+) channel in cultured human proximal tubule cells. IFN-gamma exhibited a delayed suppression and an acute stimulation of K(+) channel activity, whereas IL-1beta acutely suppressed the channel activity. Furthermore, these cytokines suppressed gene expression of the renal outer medullary potassium channel. The renal tubular K(+) channels are functionally coupled to the coexisting transporters. Therefore, the effects of cytokines on renal tubular transporter activity should also be taken into account, when interpreting their effects on K(+) channel activity. PMID- 22042039 TI - A comparison of the teratogenicity of methylmercury and selenomethionine injected into bird eggs. AB - Methylmercury chloride and seleno-L-methionine were injected separately or in combinations into the fertile eggs of mallards (Anas platyrhynchos), chickens (Gallus gallus), and double-crested cormorants (Phalacrocorax auritus), and the incidence and types of teratogenic effects were recorded. For all three species, selenomethionine alone caused more deformities than did methylmercury alone. When mallard eggs were injected with the lowest dose of selenium (Se) alone (0.1 MUg/g), 28 of 44 embryos and hatchlings were deformed, whereas when eggs were injected with the lowest dose of mercury (Hg) alone (0.2 MUg/g), only 1 of 56 embryos or hatchlings was deformed. Mallard embryos seemed to be more sensitive to the teratogenic effects of Se than chicken embryos: 0 of 15 chicken embryos or hatchlings from eggs injected with 0.1 MUg/g Se exhibited deformities. Sample sizes were small with double-crested cormorant eggs, but they also seemed to be less sensitive to the teratogenic effects of Se than mallard eggs. There were no obvious differences among species regarding Hg-induced deformities. Overall, few interactions were apparent between methylmercury and selenomethionine with respect to the types of deformities observed. However, the deformities spina bifida and craniorachischisis were observed only when Hg and Se were injected in combination. One paradoxical finding was that some doses of methylmercury seemed to counteract the negative effect selenomethionine had on hatching of eggs while at the same time enhancing the negative effect selenomethionine had on creating deformities. When either methylmercury or selenomethionine is injected into avian eggs, deformities start to occur at much lower concentrations than when the Hg or Se is deposited naturally in the egg by the mother. PMID- 22042038 TI - Aldosterone stimulates nuclear factor-kappa B activity and transcription of intercellular adhesion molecule-1 and connective tissue growth factor in rat mesangial cells via serum- and glucocorticoid-inducible protein kinase-1. AB - Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. To determine the signaling pathway of aldosterone in relation to fibrosis and inflammation in mesangial cells, we investigated the effects of aldosterone on expression and activation of serum- and glucocorticoid-inducible protein kinase-1 (SGK1), the activation of nuclear factor-kappa B (NF-kappaB activation, and the expressions of intercellular adhesion molecule-1 (ICAM-1) and connective tissue growth factor (CTGF). Aldosterone stimulated SGK1 expression, phosphorylation (Ser-256), and kinase activity. The increments of phosphorylation and expression of SGK1 induced by aldosterone were inhibited by mineralocorticoid receptor (MR) inhibitor (eplerenone). Aldosterone stimulated NF-kappaB activity measured by NF-kappaB responsive elements, luciferase assay, and the levels of inhibitor of kappa B (IkappaB) phosphorylation. This aldosterone-induced activation of NF-kappaB was inhibited by the transfection of dominant-negative SGK1. Furthermore, aldosterone augmented the promoter activities and protein expressions of ICAM-1 and CTGF. The effects of aldosterone on ICAM-1 and CTGF promoter activities and protein expressions were inhibited by the transfection of dominant-negative SGK1 and dominant-negative IkappaBalpha. We also found that the MR antagonist significantly ameliorated the glomerular injury and enhancements in SGK1, ICAM-1, and CTGF expressions induced by 1% sodium chloride and aldosterone in vivo. In conclusion, our findings suggest that aldosterone stimulates ICAM-1 and CTGF transcription via activation of SGK1 and NF-kappaB, which may be involved in the progression of aldosterone-induced mesangial fibrosis and inflammation. MR antagonists may serve as useful therapeutic targets for the treatment of glomerular inflammatory disease. PMID- 22042040 TI - Hepatic concentrations of inorganic contaminants and their relationships with nutrient reserves in autumn-migrant common loons at Lake Erie. AB - Common loons (Gavia immer) are piscivorous, high-trophic level feeders that bioaccumulate inorganic contaminants at concentrations that can negatively impact their health and reproduction. Concentrations of inorganic contaminants, especially mercury (Hg), in blood, organs, and muscle have been quantified in common loons on breeding grounds, but these data are limited for migrating loons. We investigated sex- and age-related hepatic concentrations of inorganic contaminants in common loons (n = 53) that died from botulism and were salvaged at a Great Lakes staging area (i.e., Long Point, Lake Erie) during November 2005. We also investigated if hepatic concentrations of inorganic contaminants influenced lipid, protein, and mineral in our sample of migrant common loons. Last, we determined if there was correlation between Hg and selenium (Se). Consistent with data from breeding grounds, mean concentrations of Hg in liver were approximately 2.5 times greater in adult ([Formula: see text] = 14.64 +/- 16.69 MUg g(-1)) compared with juvenile birds ([Formula: see text] = 3.99 +/- 2.27 MUg g(-1)). Elements detected in liver at potentially harmful levels were Hg and Se, of which lipid reserves varied negatively with Hg concentrations but positively with Se concentrations. In addition, Hg and Se were correlated (r = 0.65) at greater then a demethylation threshold (total Hg >= 8.5 MUg g(-1) dw) but not lower than that. Concentrations of inorganic contaminants did not influence protein and mineral levels in our sample of common loons. Our results suggest that Hg accumulation negatively affects lipid levels in migrant common loons. Results are also consistent with a nontoxic Hg-Se protein complex protecting loons migrating through areas that are relatively Se rich. Although the acquisition of Se during the nonbreeding season may decrease the toxicity of Hg, future research should consider the synergistic Hg-Se effect on reproduction in common loons that migrate through Se-rich locales, such as the Great Lakes. PMID- 22042041 TI - Dose-creep of Infliximab during psoriasis treatment: an observational study. PMID- 22042042 TI - Municipal solid waste generation in growing urban areas in Africa: current practices and relation to socioeconomic factors in Jimma, Ethiopia. AB - As one of cities in the developing countries, a rapid population growth and industrial activities pose many environmental challenges for Jimma city, Ethiopia. One aspect of urban growth posing a threat on sustainable development is poor solid waste management, which results in environmental pollution. The purpose of this study is to evaluate the quantity, composition, sources of waste generated, their current disposal practices, and to recommend appropriate management technologies. The total waste generated daily in Jimma city was ca. 88,000 kg, and the average per capita generation rate was 0.55 +/- 0.17 kg/capita/day. Eighty-seven percent of the waste was produced by households and 13% by institutions, and a negligible fraction (0.1%) was generated by street sweepings. During the rainy season, 40% more waste was generated than in the dry season because of the increased availability of agricultural food product. Further analysis showed that biodegradable organic waste constitutes 54% by weight with an average moisture content of 60% that falls within the required limits for composting. The nonbiodegradable components constitute 46% of which 30% of it was nonrecyclable material. Only 25% of the community uses municipal containers for disposal at the selected landfill site. Fifty-one percent of the households disposed their waste in individually chosen spots, whereas 22% burned their waste. Finally 2% of households use private waste collectors. The socioeconomic analysis showed that higher family income and educational status is associated more with private or municipal waste collection and less with the application of backyard or open dumping. These insights into generated waste and management practice in Jimma city allow making suggestions for improved collection, treatment, and disposal methods. A primary conclusion is that the biodegradable waste is a major fraction having suitable properties for recycling. As such an economic benefit can be obtained from this waste while avoiding the need for disposal. PMID- 22042043 TI - Modeling pollen tube growth: feeling the pressure to deliver testifiable predictions. AB - The frequency and amplitude of oscillatory pollen tube growth can be altered by changing the osmotic value of the surrounding medium. This has motivated the proposition that the periodic change in growth velocity is caused by changes in turgor pressure. Using mathematical modeling we recently demonstrated that the oscillatory pollen tube growth does not require turgor to change but that this behavior can be explained with a mechanism that relies on changes in the mechanical properties of the cell wall which in turn are caused by temporal variations in the secretion of cell wall precursors. The model also explains why turgor and growth rate are correlated for oscillatory growth with long growth cycles while they seem uncorrelated for oscillatory growth with short growth cycles. The predictions made by the model are testifiable by experimental data and therefore represent an important step towards understanding the dynamics of the growth behavior in walled cells. PMID- 22042045 TI - Solitary eosinophilic granuloma of the adult lumbar spine. AB - INTRODUCTION: Eosinophilic granuloma (EG) is a benign bone tumor that rarely occurs in adults. It is usually found occurring in flat and long bones, but spine is often affected too. EG is of unknown aetiology, and the course of the disease is unpredictable. MATERIALS AND METHODS: Two cases of EG of the adult lumbar spine are reported, representing a difficult challenge for diagnosis and treatment. CONCLUSION: CT scan guided trocar biopsy allowed to achieve a definitive diagnosis, and CT scan guided intralesional infiltrations of corticosteroids were the successful treatment. PMID- 22042044 TI - The impact of halo-gravity traction on curve rigidity and pulmonary function in the treatment of severe and rigid scoliosis and kyphoscoliosis: a clinical study and narrative review of the literature. AB - INTRODUCTION: The treatment of rigid and severe scoliosis and kyphoscoliosis is a surgical challenge. Presurgical halo-gravity traction (HGT) achieves an increase in curve flexibility, a reduction in neurologic risks through gradual traction on a chronically tethered cord and an improvement in preoperative pulmonary function. However, little is known with respect to the ideal indications for HGT, its appropriate duration, or its efficacy in the treatment of rigid deformities. MATERIALS AND METHODS: To investigate the use of HGT in severe deformities, we performed a retrospective review of 45 patients who had severe and rigid scoliosis or kyphoscoliosis. The analysis focused on the impact of HGT on curve flexibility, pulmonary function tests (PFTs), complications and surgical outcomes in a single spine centre. RESULTS: PFTs were used to assess the predicted forced vital capacity (FVC%). The mean age of the sample was 24+/-14 years. 39 patients had rigid kyphoscoliosis, and 6 had scoliosis. The mean apical rotation was 3.6 degrees +/-1.4 degrees , according to the Nash and Moe grading system. The curve apices were mainly in the thoracic spine. HGT was used preoperatively in all the patients. The mean preoperative scoliosis was 106.1 degrees +/-34.5 degrees , and the mean kyphosis was 90.7 degrees +/-29.7 degrees . The instrumentation used included hybrids and pedicle screw-based constructs. In 18 patients (40%), a posterior concave thoracoplasty was performed. Preoperative PFT data were obtained for all the patients, and 24 patients had >=3 assessments during the HGT. The difference between the first and the final PFTs during the HGT averaged 7.0+/-8.2% (p<.001). Concerning the evolution of pulmonary function, 30 patients had complete data sets, with the final PFT performed, on average, 24 months after the index surgery. The mean preoperative FVC% in these patients was 47.2+/-18%, and the FVC% at follow-up was 44.5+/-17% (a difference that did not reach statistical significance). The preoperative FVC% was highly predictive of the follow-up FVC% and the response during HGT. The mean flexibility of the scoliosis curve during HGT was only 14.8+/-11.4%, which was not significantly different from the flexibility measures achieved on bending radiographs or Cotrel traction radiographs. In rigid curves, the Cobb angle difference between the first and final radiographs during HGT was only 8 degrees +/-9 degrees for scoliosis and 7 degrees +/-12 degrees for kyphosis. Concerning surgical outcomes, 13 patients (28.9%) experienced minor and 15 (33.3%) experienced major complications. No permanent neurologic deficits or deaths occurred. Additional surgery was indicated in 12 patients (26.7%), including 7 rib-hump resections. At the final evaluation, 69% of the patients had improved coronal balance, and at a mean follow-up of 33+/-23.3 months, 39 patients (86.7%) were either satisfied or very satisfied with the overall outcome. CONCLUSION: The improvement of pulmonary function and the restoration of sagittal and coronal balance are the main goals in the treatment of severe and rigid scoliosis and kyphoscoliosis. A review of the literature showed that HGT is a useful tool for selected patients. Preoperative HGT is indicated in severe curves with moderate to severe pulmonary compromise. HGT should not be expected to significantly improve severe curves without a prior anterior and/or posterior release. The data presented in this study can be used in future studies to compare the surgical and pulmonary outcomes of severe and rigid deformities. PMID- 22042046 TI - Cobalt-phosphate complexes catalyze the photoelectrochemical water oxidation of BiVO4 electrodes. AB - BiVO(4) semiconductor electrodes were coupled with cobalt-phosphate complexes (CoPi) to enhance the photoelectrochemical (PEC) performance for water oxidation reaction. CoPi was deposited on a 550 nm-thick BiVO(4) film via electrodeposition (ED) and photodeposition (PD) methods for comparison of their effects. The CoPi on BiVO(4) exhibited Co : P atomic ratios of approximately 1 : 7 for the electrodeposited sample and approximately 1 : 18 for the photodeposited sample, and Co(2+) and Co(3+) co-existed in both samples. Optimized CoPi ED resulted in a CoPi overlayer of approximately 850 nm thick, which showed an electrochromic-like behavior that was likely due to limited access of phosphate into BiVO(4) across the CoPi layer. Optimized CoPi PD, however, had very thin and rather uniform CoPi dispersion and did not show electrochromic-like behavior. Despite the lesser amount of CoPi, the PEC performance of BiVO(4)/CoPi (PD) was comparable to that of BiVO(4)/CoPi (ED). Real-time measurements of the headspace molecular oxygen that evolved from water oxidation indicated that CoPi enhances O(2) production and photocurrent generation at BiVO(4) by a factor of around 15 and a maximum of 20, respectively, at 0.576 V(SCE) (equivalent to 1.23 V(RHE)) under air mass 1.5 irradiation (400 mW cm(-2)). Prolonged irradiation of BiVO(4)/CoPi (ED) resulted in a reduced Co : P ratio to 1 : 1.77 without changing the mixed valency of Co(II/III). This finding indicates that incorporation of phosphate into the CoPi was kinetically slower than water oxidation. The primary role of CoPi has been suggested as a hole-conducting electrocatalyst making the photogenerated electrons more mobile and, consequently, increasing conductivity and boosting the PEC water oxidation performance of BiVO(4). PMID- 22042047 TI - Fluid and electrolyte management: putting a plan in motion. AB - Fluid and electrolyte management is challenging for clinicians, as electrolytes shift in a variety of settings and disease states and are dependent on osmotic changes and fluid balance. The development of a plan for managing fluid and electrolyte abnormalities should start with correcting the underlying condition. In most cases, this is followed by an assessment of fluid balance with the goal of achieving euvolemia. After fluid status is understood and/or corrected, electrolyte imbalances are simplified. Many equations are available to aid clinicians in providing safe recommendations or at least to give a starting point for correcting the abnormalities. However, these equations do not take into consideration the vast differences between clinical scenarios, thus making electrolyte management more challenging. The supplementation plan, whether delivered intravenously or orally, must include an assessment of renal and gastrointestinal function, as most guidelines are established under the assumption of normal digestion, absorption and excretion. After the plan is developed, frequent monitoring is vital to regain homeostasis. A fluid and electrolyte management plan developed by a multidisciplinary team is advantageous in promoting continuity of care and producing safe outcomes. PMID- 22042048 TI - Retinol binding protein: marker for insulin resistance and inflammation postburn? AB - INTRODUCTION: Burn injury leads to vast changes in both metabolic and inflammatory responses and is associated with increased morbidity and mortality. Insulin resistance (IR) and hyperglycemia are major components of the hypermetabolic response found in burn-injured patients and subsequently contribute to adverse outcomes. Studies have shown that increased systemic retinol binding protein (RBP) levels are associated with IR and hyperinflammation in diabetic and obese patients. The aim of this study was to determine RBP profiles and to test the hypothesis that elevated RBP levels are associated with both IR and the inflammatory response in burned patients. METHODS: RBP was measured in 372 patients during the acute stay postburn. Patients' demographics, glucose levels, and insulin administration were recorded. Cytokines, hormones, plasma proteins, and organ markers were measured. The average of all measurements of RBP (2.1 mg/dL) was used to divide patients into high and low groups. Statistical analysis was performed by Student t test. Statistical significance was accepted at P < .05. RESULTS: Fifty-one patients (high group) had elevated RBP levels during acute hospitalization and demonstrated a significant higher incidence of multiorgan failure, sepsis, and mortality (P < .05). Moreover, in the high group, a significant increase of IR, inflammatory cytokines, and catabolic and organ-specific markers were detected (P < .05). CONCLUSIONS: Increased RBP levels postburn correlate with increased IR, inflammatory and catabolic responses, incidence of multiorgan failure, and mortality. RBP may be a novel biomarker to monitor these detrimental responses postburn. PMID- 22042049 TI - Reduced parenteral nutrition requirements following anastomosis of a short residual colonic segment to a short jejunum. AB - A 22-year-old man suffered an acute small bowel infarct leading to extensive bowel resection, resulting in only 20 cm of jejunum to a jejunostomy, although he also had 50 cm of residual colon with a mucous fistula. The patient was out on long-term home parenteral nutrition (PN) but endured high stomal losses of 5-6 L per day and, despite all conventional measures, required 6.1 L of fluid (including PN) and 555 mmol sodium per day. Although body mass index was maintained, he suffered debilitating malaise and recurrent episodes of catheter related sepsis and also developed persistently abnormal liver function tests. He was considered a potential intestinal transplant patient, but before taking that step, he opted for reanastomosis of his residual colon to his jejunum, ending in a colostomy. At surgery, only 30 cm of additional bowel lengthening could be achieved, but despite this, the patient's stomal losses reduced to 2.5 L per day, intravenous fluid requirements reduced to 4.1 L per day, and liver function normalized. The patient also gained 7.5 kg despite no change in PN caloric prescription, and his quality of life was dramatically enhanced. The case illustrates that even a small length of colon can grant significant improvements, probably via improvements in small bowel transit and adaptive changes, better sodium and water resorption with decreased hyperaldosteronism, and enhanced energy and nitrogen recovery. Reanastomosis of defunctioned colon should therefore always be considered a management option in short bowel syndrome. PMID- 22042050 TI - Route and type of nutrition and surgical stress influence secretory phospholipase A2 secretion of the murine small intestine. AB - BACKGROUND: The function of secretory phospholipase A2 (sPLA2) is site dependent. In tissue, sPLA2 regulates eicosanoid production; in circulation, sPLA2 primes neutrophils; and in the intestinal lumen, sPLA2 provides innate bactericidal immunity as a defensin-related protein. Since parenteral nutrition (PN) primes leukocytes while suppressing intraluminal mucosal immunity, the authors hypothesized that (1) PN would diminish luminal sPLA2 activity but increase activity in intestinal tissue and serum and (2) stress would accentuate these changes. METHODS: Mice received chow, a complex enteral diet (CED), intragastric PN (IG-PN), or PN in experiment 1 and chow, chow+stress, PN, or PN+stress in experiment 2. RESULTS: In experiment 1, luminal sPLA2 activity was greatest in chow and decreased in CED, IG-PN, and PN, with PN lower than CED and IG-PN. Compared to that after chow, serum sPLA2 activity dropped after CED, IG-PN, and PN. Serum sPLA2 was higher in portal than systemic serum. In experiment 2, PN lowered luminal sPLA2 activity vs chow. Stress lowered luminal sPLA2 activity in chow, without change in PN. Following stress, luminal immunoglobulin A increased in chow but not PN. Serum sPLA2 activity increased in PN. CONCLUSIONS: PN attenuates sPLA2 activity in intestinal fluid, consistent with suppressed innate mucosal defense. Stress suppresses luminal fluid sPLA2 activity in chow but not the immunoglobulin A response; PN impairs both. Stress significantly elevates serum sPLA2 in PN-fed mice, consistent with known increased neutrophil priming with PN. PN reduces innate bactericidal immunity of the gut but upregulates serum proinflammatory products poststress. PMID- 22042055 TI - Amyloid peptides incorporating a core sequence from the amyloid beta peptide and gamma amino acids: relating bioactivity to self-assembly. AB - A series of heptapeptides comprising the core sequence Abeta(16-20), KLVFF, of the amyloid beta peptide coupled with paired N-terminal gamma-amino acids are investigated in terms of cytotoxicity reduction and binding to the full Abeta peptide, both pointing to inhibition of fibrillisation for selected compounds. This is related to the self-assembly capacity of the heptapeptides. PMID- 22042057 TI - Cultured human mast cells are heterogeneous for expression of the high-affinity IgE receptor FcepsilonRI. AB - OBJECTIVE: We determined the density of FcepsilonRI on mast cells cultured from cord (CBMC) and peripheral blood (PBMC) and studied the kinetics of the response through FcepsilonRI. METHODS: Mast cells were cultured from CD133+ progenitors from peripheral or cord blood. FcepsilonRI was stabilized by culture with 2 MUg/ml IgE. Cells were activated by addition of anti-FcepsilonRI antibody (1 ng/ml-10 MUg/ml). Maximal activation, sensitivity, and cooperativity were determined. RESULTS: All cultures were homogeneous for tryptase and metachromasy. All cells expressing FcepsilonRI could be activated by cross-linking FcepsilonRI to upregulate CD63. PBMC bind 203,000 molecules of IgE/cell. Stabilization of FcepsilonRI with IgE doubled the number of CD63+ cells (p = 0.0001) and increased the sensitivity (from 0.083 to 0.013 MUg/ml anti-FcepsilonRI) and the slope factor (from 10.8 to 68) of PBMC but not of CBMC. Anti-IgE reversed these effects (p = 0.0002) but did not reduce activation levels below that of cell lines not stabilized with IgE. CONCLUSION: Baseline expression of FcepsilonRI is independent of anti-IgE. The fraction of PBMC that binds high levels of IgE can be activated through FcepsilonRI. PMID- 22042058 TI - From stress to postpartum mood and anxiety disorders: how chronic peripartum stress can impair maternal adaptations. AB - The peripartum period, in all mammalian species, is characterised by numerous adaptations at neuroendocrine, molecular and behavioural levels that prepare the female for the challenges of motherhood. These changes have been well characterised and, while they are necessary to ensure the survival and nurturance of the offspring, there is growing belief that they are also required for maternal mental health. Thus, while increased calmness and attenuated stress responsivity are common characteristics of the peripartum period, it also represents a time of increased susceptibility to mood disorders. While a number of risk factors for these disorders are known, their underlying aetiology remains poorly understood, due at least in part to a lack of appropriate animal models. One translatable risk factor is stress exposure during the peripartum period. In the following review we first describe common peripartum adaptations and the impact postpartum mood disorders have on these. We then discuss the known consequences of peripartum stress exposure on such maternal adaptations that have been described in basic research. PMID- 22042059 TI - Comparison between one injection and three monthly injections of intravitreal bevacizumab for myopic choroidal neovascularization. AB - AIM: To compare the effects of one intravitreal bevacizumab (IVB) injection with three monthly injections for myopic choroidal neovascularization. METHODS: Group A included 13 patients treated with one IVB injection; group B included 19 patients treated with three monthly 1.25-mg IVB injections. All patients were followed monthly for 12 months with additional injections performed as needed. The best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) on optical coherence tomography were evaluated before and after treatment. RESULTS: The mean logMAR BCVA improved from 0.59 to 0.49 at 12 months in group A (p = 0.21) and from 0.65 to 0.29 in group B (p < 0.001); the improved logMAR BCVA differed significantly between the groups (p < 0.05). The mean CFT decreased from 231 MUm at baseline to 150 MUm at 12 months in group A (p < 0.05) and from 279 to 156 MUm in group B (p < 0.001). During the follow-up, 6 of 13 eyes in group A and 5 of 19 eyes in group B received additional injections. CONCLUSIONS: Treatment starting with three monthly IVB injections may achieve better functional outcomes with fewer retreatments compared with treatment starting with one IVB injection. PMID- 22042056 TI - Factors associated with insulin resistance among children and adolescents perinatally infected with HIV-1 in the pediatric HIV/AIDS cohort study. AB - BACKGROUND/AIMS: Because of prior inconsistent findings, we studied a large cohort of HIV-infected children to determine: (1) prevalence of insulin resistance (IR); (2) anthropometric and clinical correlates of IR, and (3) concomitant abnormalities of glucose tolerance. METHODS: The study population consisted of 451 children from the Pediatric HIV/AIDS Cohort Study. The outcome of interest was HOMA-IR. Covariates included demographic, metabolic, growth, body composition, HIV laboratory tests, and treatment characteristics. Children meeting triggers for IR underwent oral glucose tolerance tests and hemoglobin A1c (HbA1c) measurements. RESULTS: Among 402 children with glucose and insulin measurements, 15.2% had IR of whom 79% were pubertal. IR was associated with higher alanine aminotransferase, body mass index, and nadir CD4%, Tanner stage 5, and ever having received amprenavir. Of those with IR, three had impaired fasting glucose (IFG), three impaired glucose tolerance (IGT), one IFG and IGT, none diabetic glucose tolerance, and three HbA1c between 6.1 and 6.5%. CONCLUSION: In our cohort of HIV-infected adolescents, we observed a 15.2% prevalence of IR more closely linked to obesity than any other variable. This finding mirrors the high prevalence of obesity-mediated IR in American youth. However, associations with CD4 count and use of protease inhibitors may indicate some effect of HIV and/or its treatment. PMID- 22042060 TI - Quantifying cognitive decrements caused by cranial radiotherapy. AB - With the exception of survival, cognitive impairment stemming from the clinical management of cancer is a major factor dictating therapeutic outcome. For many patients afflicted with CNS and non-CNS malignancies, radiotherapy and chemotherapy offer the best options for disease control. These treatments however come at a cost, and nearly all cancer survivors (~11 million in the US alone as of 2006) incur some risk for developing cognitive dysfunction, with the most severe cases found in patients subjected to cranial radiotherapy (~200,000/yr) for the control of primary and metastatic brain tumors. Particularly problematic are pediatric cases, whose long-term survival plagued with marked cognitive decrements results in significant socioeconomic burdens. To date, there are still no satisfactory solutions to this significant clinical problem. We have addressed this serious health concern using transplanted stem cells to combat radiation induced cognitive decline in athymic rats subjected to cranial irradiation. Details of the stereotaxic irradiation and the in vitro culturing and transplantation of human neural stem cells (hNSCs) can be found in our companion paper (Acharya et al., JoVE reference). Following irradiation and transplantation surgery, rats are then assessed for changes in cognition, grafted cell survival and expression of differentiation-specific markers 1 and 4-months after irradiation. To critically evaluate the success or failure of any potential intervention designed to ameliorate radiation-induced cognitive sequelae, a rigorous series of quantitative cognitive tasks must be performed. To accomplish this, we subject our animals to a suite of cognitive testing paradigms including novel place recognition, water maze, elevated plus maze and fear conditioning, in order to quantify hippocampal and non-hippocampal learning and memory. We have demonstrated the utility of these tests for quantifying specific types of cognitive decrements in irradiated animals, and used them to show that animals engrafted with hNSCs exhibit significant improvements in cognitive function. The cognitive benefits derived from engrafted human stem cells suggest that similar strategies may one day provide much needed clinical recourse to cancer survivors suffering from impaired cognition. Accordingly, we have provided written and visual documentation of the critical steps used in our cognitive testing paradigms to facilitate the translation of our promising results into the clinic. PMID- 22042061 TI - [Pseudohypoaldosteronism type 1: an uncommon electrolyte emergency. Report of four cases]. AB - Pseudohypoaldosteronism type 1 is a rare syndrome of resistance to aldosterone manifested by salt wasting, hyponatremia, hyperkalemia, hyperchloremic metabolic acidosis, and hiperreninemic hyperaldosteronism. The syndrome may be genetic, secondary to uropathies and urinary tract infection among other causes or it may occur sporadically. The salt wasting may be systemic and severe or localized to the kidney usually with better prognosis. The clinical picture is prevalent in the first seven months of life, failure to thrive and recurrent vomiting are usually the common clinical signs, an electrolyte emergency in the form of hypovolemic shock, hyperkalemic cardiac arrhythmias and hyponatremic seizures is rare. Four patients presenting with an electrolyte emergency are reported. PMID- 22042062 TI - [Pachydermodactyly: case report]. AB - Pachydermodactyly is a type of benign digital fibromatoses, a rare condition that affects mostly young men. The cause is unknown but some authors suggest that traumatism can be involved. A 16-year-old man presented with symmetrical painless swellings on the fingers of both hands. He used to rub his fingers together. The control of living habits must be enphasized in order to avoid repeteated injuries. Hence, our consultation work is with the patient and his family. We describe a new case of pathology with a common clinical diagnosis, whose ignorance could lead us to carry out unnecesary tests involving inconvenience to the patient. It is important to emphasize the modification of the patient's living habits in order to achieve its improvement. PMID- 22042063 TI - [Unilateral nasal obstruction in children: Pai syndrome]. AB - Unilateral obstruction of the nasal cavity in children is mainly caused by the introduction of foreign bodies further stated with rhinorrhea and fetid odor. Less commonly, it can be traumatic, neoplastic, due to congenital malformation or iatrogenic. Symptoms of congenital intranasal mass may present at birth, or go unnoticed and be a finding in a routine pediatric examination. Patient evaluation should include imaging studies to guide the diagnosis and rule out intracranial extension. A syndrome associated with congenital nasal tumor should be suspected when other abnormalities are present. Pai syndrome is a rare genetic disorder. Its manifestations are craniofacial being congenital nasal polyp his main marker. We present a patient with unilateral nasal respiratory failure secondary to congenital nasal lipoma, with craniofacial anomalies belonging to Pai syndrome. Nasal obstruction was successfully surgically resolved. PMID- 22042064 TI - [Priapism in pediatrics: initial presentation of chronic myeloid leukemia]. AB - Priapism is a prolonged penis erection, triggered by sexual stimulation or not; it is uncommon in children, but its knowledge is of great importance since it may lead to suspect serious diseases, such as leukemia, and it can lead to permanent erectile dysfunction if appropriate treatment is not timely done. We present the case of a 16-year-old boy with priapism which lead to a diagnosis of chronic myeloid leukemia. Knowledge of an uncommon pathology in children, like priapism, it is very important in order to establish the suitable and timely treatment, to prevent the irreversible sequelaes and complications of this disease. PMID- 22042065 TI - [Interdisciplinary approach in Pediatrics at 100 years of the Sociedad Argentina de Pediatria]. PMID- 22042066 TI - [Second-hand smoking, knowledge and legislation]. PMID- 22042067 TI - [Breast feeding and sudden infant death syndrome prevention]. PMID- 22042068 TI - [Body mass index and blood pressure at one year of age by birth weight, weight gain and early feeding patterns]. AB - INTRODUCTION: Abnormal early growth patterns have been associated with overweight and other related diseases along the life course. OBJECTIVE: To analyze the association between changes in growth patterns and nutrition status during the second semester of life and blood pressure (BP), according to weight for gestational age (GE), and early dietary patterns, in a sample of healthy children. METHODS: Prospective study from a sample of healthy children followed between 6-12 months of age, between 10/07 and 3/08 at Hospital P. Elizalde. Gender, weight and gestational age at birth, weight, height and body mass index (BMI, WHO ref.) at 6, 9 and 12 months, length of breastfeeding, and blood pressure (BP) at 12 months of age were assessed. RESULTS: One hundred twenty infants were follow- up. Variation in standardized BMI between 6-12 months of age is the main predictor of BMI at 12 months of age (R2 0.12; Coef b 0.34; error estandar 0.11; p 0.006). The interaction term between length of breastfeeding and small for gestational age is the main predictor of changes in BMI between 6-12 months of age (R2 0.11; Coef b -0.15; error estandar 0.04, p < 0.001). Each standardized unit increment in BMI implies an increase of 1.76 mmHg in diastolic blood pressure at one year. CONCLUSION: Length of gestation, birth weight and early feeding patterns are associated with weight gain during the first year of life, which is linked at the same time to BMI and BP. The positive change in BMI was associated with shorter duration of breastfeeding and this in turn to higher blood pressure at one year. PMID- 22042069 TI - [Nosocomial infections in a neonatal unit: surveillance program]. AB - INTRODUCTION: Nosocomial infections in neonatal units are frequent and require having a surveillance program which allows detection and implementation of preventive strategies. OBJECTIVE: To determine the incidence and distribution of hospital infections and the rate of use of devices in a neonatal unit compared with international standards. METHODS: Epidemiological, observational, analytical, prospective cohort study. We developed and carried out a monitoring program, stratifying infants by birth weight, recording the use of central catheters, mechanical ventilation, parenteral nutrition and bladder catheter. We calculated the total patient days, the device utilization rates and episodes of hospital infection. The data were compared with those of the National Nosocomial Infection Surveillance. RESULTS: 1530 infants were admitted to the Neonatal Care Unit from 01/01/2006 to 31/12/2008 totaling 22 237 days patients. We identified 138 episodes of hospital infections, adjusted overall rate 6.23 episodes per 1000 patient/days. Overall rates of devices' use were: central catheter 32.3%, mechanical ventilation 14.2%, bladder catheter 4.6%. The overall rate of nosocomial infection associated with central catheter was 8.6 0/00. All groups had rates within the published rates, except the group of infants <1000 grams (19.7 0/00), that exceeded the 90th percentile. With regard to ventilator associated pneumonia (overall rate 1.90/00), rates were comparable. CONCLUSION: The description of the occurrence and distribution of nosocomial infections and their association with risk factors could be determined and generally showed to be found within the published percentiles. PMID- 22042070 TI - [Non-symbolic addition in preschool children from Argentina]. AB - INTRODUCTION: Children take years to learn symbolic arithmetic. Nevertheless, such as animals and human adults, infants and children can represent approximate number in arrays of objects and sequences of events, and use these capacities to perform approximate addition and subtraction. OBJECTIVE: To evaluate whether preschool children without formal education could perform non-symbolic additions, through abstract representations. METHODS: We evaluated 17 preschoolers from a private kindergarten recruited from the city of Buenos Aires. They had to add to groups of blue dots, and then compare their addition with a third group of red dots, determining if the blue or the red dots were more numerous. We measured accuracy of responses of each child. RESULTS: Across all the problems, children performed well above chance (67.89%, chance= 50%, t(16)= 6.89, p <0.001), showing the characteristic ratio effect [F(1, 16)= 8.45, p <0.01, ANOVA], and without resort to non-arithmetic strategies. CONCLUSIONS: This study provides further evidence regarding the non-symbolic arithmetic skill present before formal education, and together with recent research, raises important contributions in education, trying to understand how children learn mathematics and to establish new methods of teaching. PMID- 22042071 TI - [What do we call health and mental disorders in pediatrics? A reflexive outlook on the psychiatry diagnosis and its relation with the new subjetive theories in children]. AB - Conceptual basis for Infant and Juvenile Psychiatry are discussed taking into account the clear differences in the definition of Health and Mental Illness. It is emphasized that the mind is not simply a biological phenomenon and, thus, there is a need for assessment parameters that include subjective states, as well as a shift from lineal thoughts to complex forms that include the value of experience, fate, and event, amongst other ideas. This allows a change of perspective: the acknowledgement of the Positive Indicators of Mental Health and not only the absence of symptoms or disorders. PMID- 22042072 TI - [Lymphatic malformations: percutaneus treatment with bleomycin]. AB - Lymphatic malformations are developmental abnormalities of the lymphatic system, which tend to complicate during their evolution. In the last decade, therapy with sclerosing agents has gained popularity over surgery due to its effectiveness, fewer complications, and excellent cosmetic results. We present a series of 24 patients treated with percutaneous bleomycin injection. Results were excellent (volume reduction >= 95%, without symptoms) in 12 patients, good (volume reduction between 50% and 95%, without symptoms) in 5 patients, fair (volume reduction <50%, without symptoms) in 4 patients, and poor (no change in volume from baseline and persistence of symptoms) in 3 patients. These results were directly related to the type of lymphatic malformation. The complications found had little clinical relevance. Sclerotherapy with bleomycin is an effective and safe treatment for patients with unicystic or macrocystic lymphatic malformations. It could also be used in patients with microcystic or cavernous lymphatic malformation undergoing surgery to reduce both the malformation size and postoperative lymphorrhea, and in postoperative symptomatic patients whose malformation could not be totally resected. PMID- 22042073 TI - [The prognosis for children of mothers with preeclampsia. Part 1: short-term effects]. AB - Preeclampsia affects between 4 to 8% of all human pregnancies. It compromised both mothers and offspring beyond perinatal period. This is the first o two papers related whit this phenomenon and shows the available evidence about the effect of preeclampsia over the preeclamptic offspring from cohort studies. It is devoted to develop all facts related with respiratory distress syndrome, sepsis, neurological issues and other problems presented over neonatal period. PMID- 22042074 TI - [Current concepts in perinatal brachial plexus palsy. Part 2: late phase. Shoulder deformities]. AB - The incidence of obstetric brachial palsy is high and their sequelaes are frequent. Physiotherapy, microsurgical nerve reconstruction and secondary corrections are used together to improve the shoulder function. The most common posture is shoulder in internal rotation and adduction, because of the antagonist weakness. The muscle forces imbalance over the osteoarticular system, will result in a progressive glenohumeral joint deformity which can be recognized with a magnetic resonance image. Tendon transfers of the internal rotators towards the external abductor/rotator muscles, has good results, but has to be combined with antero-inferior soft-tissue releases, if passive range of motion is limited. PMID- 22042075 TI - [Facebook and Twitter, are they already in the pediatrician's office? Survey on the use of social networks]. AB - The Web 2.0 has democratized the use of services and applications, being Facebook and Twitter its leading exponents and it even has been proposed that there exists a Medicine 2.0. A survey for professionals subscribed to discussion lists of Argentine Pediatric Society (SAP) and for visitors to the Website was carried out to know the use of Web 2.0. In 377 responses (76% pediatricians), 81.3% of users use Facebook and Twitter 16.5%. Facebook is used in an 85% for personal purposes, while the professional use of it is 41.2%. Pediatricians frequently use other web 2.0 applications such as YouTube (80.3%), sharing images (52.2%) and listening to Podcasts (34.8%). Around 50% of the professionasl surveyed showed interest in receiving information on the professional activites carried out by SAP. Clinicians should recognize these new tools to incorporate them into their professional activities. PMID- 22042076 TI - [Fungal infections in a pediatric burn care]. AB - OBJECTIVE: Retrospective description of fungal infections in a specialized intensive care burn unit. RESULTS: A total of 41 (21%) of 195 patients admitted from January 2002 to March 2006 developed fungal infections at any site. The median age of patients was 48 months (interquartile range: 18-84), and the affected burn surface was 40% (interquartile range 30 and 65% The median time lapse between admission and fungal infections was 13 days (interquartile range 8 20 d) The most frequent site of isolation was burnt wound in 38 patients (93%) and in blood cultures in 3 patients (7%). In 93% of patients bacterial infections were also found. The predominant fungus recovered was Candida spp in 20 patients (49%); followed by Aspergillus sp in 6 patients (15%), Anphotericin B was the drug of choice. The median time of complete treatment was 23 days (interquartile range: 15-30). One patient died (2%) from causes related to fungal infection. CONCLUSION: A total of 41 (21%) of 195 patients admitted from January 2002 to March 2006 developed fungal infections. Candida sp was the most frequently found. Mortality was low. PMID- 22042077 TI - [The handicapped adolescents and their sexuality]. AB - Adolescents with different types of motor handicapping have desires, needs, and feelings, and have the right to express them in the best possible and acceptable way. Sexual education provided to young people with these handicaps is generally more limited than that offered to their normal peers. These adolescents are inadvertently excluded, and some may find difficult to establish a steady couple relationship. Health-care professionals should bear in mind the needs and worries of their handicapped patients and include the topic of sexuality in their visits from the start insisting on the fact that it is a normal activity in the context of a variety of associated problems. PMID- 22042078 TI - [Duchenne muscular dystrophy]. PMID- 22042080 TI - [Recommendations in Neonatal Resuscitation 2011. 1rst part: initial steps - further evaluation]. PMID- 22042081 TI - Pyridoxine-derived bicyclic aminopyridinol antioxidants: synthesis and their antioxidant activities. AB - A few facile synthetic pathways for bicyclic aminopyridinol antioxidants are presented. Attachment of a long alkyl chain to the bicyclic pyridinol scaffold was established using ester linkage. Non-substituted pyrrolopyridinols and 1,3 oxazine-fused pyridinols were also synthesized as novel antioxidant scaffolds. Antioxidant activities were measured by a radical clock method and new compounds prepared are comparable to the best bicyclic aminopyridinol antioxidants. PMID- 22042082 TI - The anti-TNF-alpha antibody infliximab indirectly regulates PECAM-1 gene expression in two models of in vitro blood cell activation. AB - Chronic inflammatory bowel diseases can be successfully treated with antibodies against the acute phase mediator TNF-alpha. The process of activation and of extravasation of inflammatory cells from the blood into the 'stressed' tissue site is controlled by cytokines and chemokines, which attract leukocytes and by adhesion molecules, which mediate their attachment and transmigration toward the affected cell(s). The changes in the gene expression of adhesion molecules taking place in those cells before attachment have been less investigated. Changes of PECAM-1, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) gene expression were studied in phytohaemagglutinin (PHA)- and lipolysaccharide (LPS)-treated human peripheral blood leukocytes (PBLs), granulocytes and the human monocyte cell line U-937. Cells were treated either with PHA or with LPS in the presence or absence of infliximab and incubated with TNF-alpha, IFN-gamma and/or transforming growth factor beta (TGF-beta) and treated as above. Activation of PBLs by PHA or LPS treatment triggered a sharp upregulation of ICAM-1, VCAM-1 gene expression and a time-dependent downregulation of PECAM-1 gene expression reaching a minimum 4 h from start of the experiment. The anti-TNF-alpha antibody infliximab, by neutralizing TNF-alpha and IFN-gamma production, completely reversed PECAM-1 mRNA downregulation and ICAM-1 and VCAM-1 upregulation. Immunostaining of PBLs cytospins with antibodies against PECAM-1 and ICAM-1 confirmed RT-PCR and western blot results. PBLs IFN-gamma or TNF-alpha treatment downregulated PECAM-1 in parallel with the upregulation of ICAM-1 and VCAM-1 gene expression, whereas TGF-beta upregulated PECAM-1- and downregulated ICAM-1 and VCAM-1 gene expression counteracting the effect of TNF-alpha or IFN-gamma. Similar results were obtained in human U937 cells and in granulocyte cultures by TNF-alpha or IFN-gamma treatment. Taken together, these results suggest that infliximab, blocking TNF-alpha and IFN-gamma production, exerts its anti inflammatory effect through inhibiting downregulation of PECAM-1 gene expression and upregulation of ICAM-1 and VCAM-1 expression in leukocytes of the peripheral blood. These results also suggest that TGF-beta may thus be of therapeutic importance as an anti-inflammatory agent. PMID- 22042084 TI - Replication of Crohn's disease-associated AIEC within macrophages is dependent on TNF-alpha secretion. AB - Adherent and invasive Escherichia coli (AIEC) associated with Crohn's disease are able to survive and to replicate extensively in active phagolysosomes within macrophages. AIEC-infected macrophages release large amounts of tumour necrosis factor-alpha (TNF-alpha) and do not undergo cell death. The aim of the present study was to determine what benefit AIEC bacteria could gain from inducing the release of large amounts of TNF-alpha by infected macrophages and to what extent the neutralization of TNF-alpha could affect AIEC intramacrophagic replication. Our results showed that the amount of TNF-alpha released by infected macrophages is correlated with the load of intramacrophagic AIEC bacteria and their intracellular replication. TNF-alpha secretion was not related to the number of bacteria entering host cells because when the number of bacteria internalized in macrophage was decreased by blocking lipid raft-dependent and clathrin-coated pits-dependent endocytosis, the amount of TNF-alpha secreted by infected macrophages was not modified. Interestingly, dose-dependent increases in the number of intracellular AIEC LF82 bacteria were observed when infected macrophages were stimulated with exogenous TNF-alpha, and neutralization of TNF alpha secreted by AIEC-infected macrophages using anti-TNF-alpha antibodies induced a significant decrease in the number of intramacrophagic bacteria. These results indicate that AIEC bacteria use TNF-alpha as a Trojan horse to ensure their intracellular replication because replication of AIEC bacteria within macrophages induces the release of TNF-alpha, which in turn increases the intramacrophagic replication of AIEC. Neutralizing TNF-alpha secreted by infected macrophages may represent an effective strategy to control AIEC intracellular replication. PMID- 22042083 TI - Pentosan polysulfate inhibits atherosclerosis in Watanabe heritable hyperlipidemic rabbits: differential modulation of metalloproteinase-2 and -9. AB - Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor alpha (TNFalpha) stimulated proinflammatory responses, in particular activation of nuclear factor kappaB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFalpha-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis. PMID- 22042085 TI - HBcAg induces PD-1 upregulation on CD4+T cells through activation of JNK, ERK and PI3K/AKT pathways in chronic hepatitis-B-infected patients. AB - Hyper-expression of programmed death-1 (PD-1) is a hallmark of exhausted T cells. In chronic hepatitis-B virus (HBV)-infected patients, PD-1 upregulation on T cells was often observed. The mechanism of it has not been fully understood. In this study, we examined the dynamic changes of PD-1 expression on T cells during the natural history of chronic HBV infection and explored the signaling pathway of PD-1 upregulation by the hepatitis-B core antigen (HBcAg). Sixty-seven chronic HBV-infected patients were categorized into an immune tolerance group, an immune clearance group and an inactive virus carrier group, and 20 healthy volunteers were chosen as normal control group. Peripheral blood mononuclear cells from patients and healthy volunteers, and T lymphocytes from healthy volunteers were separated. Results showed that the PD-1 expression level on CD4(+)T cells in every phase of chronic HBV infection was significantly higher than that in healthy volunteers, whereas such effects were not observed on CD8(+)T cells. In the immune clearance phase, a positive correlation was found between serum HBV DNA level and the PD-1 expression level on CD4(+)T cells. In all phases, no correlation was shown between serum alanine amino transferase (ALT) level and PD 1 expression level. Phosphorylation of JNK, ERK and AKT was induced by HBcAg, and inhibitors of JNK, ERK and PI3K/AKT significantly decreased the HBcAg-induced PD 1 upregulation on CD4(+)T cells. In conclusion, the PD-1 expression level on CD4(+)T cells was upregulated in every phase of chronic HBV infection, which was induced by HBcAg through JNK, ERK and PI3K/AKT signaling pathways. PMID- 22042086 TI - Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study. AB - Tumor microvascular density (MVD) has been shown to correlate with the aggressiveness of several cancers. With the introduction of targeted anti angiogenic therapy, assessment of MVD has the potential not only as a prognostic but also as a therapeutic marker. The significance of tumor vascularity in clear cell renal cell carcinoma (ccRCC) has been debated, with studies showing contradictory results. Previous studies were limited by manual quantification of MVD within a small area of tumor. Since then, the validity of this method has been questioned. To avoid the inaccuracies of manual quantification, we employed a computerized image analysis, which allowed assessment of large areas of tumor and adjacent normal tissue. The latter was used as an internal reference for normalization. MVD and vascular endothelial growth factor (VEGF) were assessed in 57 cases of ccRCC. Sections were immunostained for CD34 and VEGF. Areas of ccRCC and normal kidney medulla were analyzed within scanned images using software that counted CD34-positive vessels and measured the intensity of VEGF staining. We obtained unadjusted values from tumoral areas and calculated adjusted values as tumor/normal ratios. Unadjusted MVD had no association with clinical outcome. However, similarly to tumor stage, higher adjusted MVD was associated with shorter disease-free survival (log-rank P=0.037, Cox P=0.02). This was significant in univariate and multivariate analyses. MVD did not correlate with tumor stage, pointing to its independent prognostic value. As expected due to the known molecular abnormalities in ccRCC, most tumors showed higher VEGF expression than normal tissue. Higher adjusted VEGF was associated with high tumor grade (P=0.049). The finding of increased MVD as an independent marker of tumor aggressiveness may prove useful in the development of new tests for prognostic and therapeutic guidance. Digital techniques can provide more accurate assessment of immunomarkers and may reveal less obvious associations. PMID- 22042087 TI - Patella tendon length after patella arthroplasty. AB - AIM: The study aimed to assess tendon length change following patello-femoral replacement (PFR) surgery and total knee replacement (TKR). METHOD: A retrospective analysis was conducted of 40 patients undergoing PFR surgery and 40 patients undergoing TKR and an unoperated control group. Immediate preoperative radiographs were compared with those at 1 year postoperatively. Intra/inter observer error was assessed in four observers. RESULT: In the unoperated patients the mean shortening was 0.6% (range 6% shortening to 3% lengthening). The mean shortening after PFR surgery was 0.1% of shortening (range 14% shortening to 11% lengthening). The mean shortening after TKR was 7.14% (range 25% shortening to 7% lengthening). CONCLUSION: Shortening of the patella tendon after PFR surgery occurs infrequently and less severely compared with TKR. LEVEL OF EVIDENCE: Level 2 prognostic study. PMID- 22042088 TI - Ultrasound-based computer navigation of the acetabular component: a feasibility study. AB - INTRODUCTION: This feasibility study investigated the accuracy of anterior pelvic reference plane (APP) registration and acetabular cup orientation in two cadavers with different BMIs. METHOD: Five observers each registered the APP five times in the 2 cadavers (BMIs: 32 kg/m(2) and 25 kg/m(2)) using an ultrasound-based navigation system. By comparison against the CT-derived reference landmarks, the errors in determining the individual landmarks defining the APP, as well as the resulting errors in the orientation of the APP and the acetabular cup orientation were determined. RESULTS: Across all measurements obtained with the ultrasound navigation system, the errors in rotation and version in determining the APP were 0.5 degrees +/- 1.0 degrees and -0.4 degrees +/- 2.0 degrees , respectively. The cup abduction and anteversion errors determined from all measurements of the five investigators for both cadavers together were -0.1 degrees +/- 1.0 degrees and -0.4 degrees +/- 2.7 degrees , respectively. The data further demonstrated a high reproducibility of the measurements for the resulting cup adduction and anteversion angle. CONCLUSION: Our preliminary results confirm that ultrasound navigation is a highly accurate tool that allows a reproducible registration of the APP and thereby enables accurate and precise intraoperative determination of the acetabular cup orientation also in patients with increased BMI. PMID- 22042089 TI - The message is clear to save an additional 100,000 lives per year in Europe: 'harder and faster for cardiopulmonary resuscitation'! PMID- 22042090 TI - How to write a good title. PMID- 22042091 TI - Cyanosis in a 9-month-old child after repair of total anomalous pulmonary venous return. AB - A 9-month-old girl presented with cyanosis after correction of total anomalous pulmonary venous return (TAPVR) to the coronary sinus in the neonatal period. During corrective surgery, the right superior vena cava (RSVC) was damaged and re anastomosed to the right atrium. Echocardiography showed increased flow velocity in the pulmonary venous confluence. Therefore, pulmonary venous obstruction was suspected. However, subsequent cardiac MRI revealed a stenosed RSVC as well as a dilated left superior vena cava (LSVC) draining from the left innominate vein into the pulmonary venous confluence. The re-recruited LSVC drained deoxygenated blood into the systemic circulation, causing cyanosis. After uncomplicated placement of a stent in the narrowed RSVC and occlusion of the LSVC, transcutaneous saturations normalised immediately. PMID- 22042092 TI - Absence of Swedish new variant Chlamydia trachomatis (nvCT) and C. trachomatis genotype distribution in Gipuzkoa, Spain, 2009-2010. PMID- 22042093 TI - Developmental changes and regional localization of Dspp, Mepe, Mimecan and Versican in postnatal developing mouse teeth. AB - It has been implicated noncollagenous proteins act as important regulators during odontogenesis. To test the hypothesis that the roles of Dspp, Mepe, Versican and Mimecan in the regulation of odontogenesis may be complementary, comparative investigations on the localization of four proteins were performed by immunohistochemical staining using mouse first molar at different developmental stages as a model. In postnatal 1- day-old mice, all the proteins, excluding Mepe, showed co-expression in young odontoblasts. At postnatal 3, strong immunoreactions for all proteins were detected in odontoblasts. Interestingly, Mepe was present within both cytoplasm and nucleus in odontoblasts. In mice older than 5 days, the expression of Dspp, Mimecan and Versican accumulated in subodontoblastic layer of the coronal pulp at high levels while the co-expression of Mepe and Mimecan significantly existed in predentin. The temporal-spatial specific pattern and unique co-localization of Dspp, Mepe, Mimecan and Versican suggest they play complementary roles during odontogenesis. PMID- 22042094 TI - Cyclooxygenase-2 expression in central giant cell lesion of the jaws: an immunohistochemical study. AB - Central Giant Cell Lesion (CGCL) is an uncommon benign jaw lesion, with uncertain etiology, and a variable clinical behavior. Studies of molecular markers of CGCL, may help understanding better the nature and behavior of this lesion, and eventually may represent a definitive target to pharmacological approach in the treatment of CGCL. Chronic inflammation has been found to mediate a wide variety of diseases including neoplasms. Among the gene products involved in the induction of the inflammatory process, Cyclooxygenase 2 (COX-2) has been shown to have a close relationship with tumorigenesis, however COX-2 expression has never been evaluated in CGCL. The aim of the study was to investigate the expression of COX-2 in CGCL. Immunohistochemical assessment for COX-2 expression was performed in 18 patients previously diagnosed with CGCL. Multinucleated giant cells (MGC) and mononucleated stromal cells (MSC) were used in the slide analysis. Among the patients studied, 10 were male and 8 were female, with a median age of 15.4 years. Lesions in the mandible were observed in 11 cases and 7 were found in the maxilla. There were 9 aggressive and 9 non-aggressive CGCLs. COX-2 immunopositivity was present in only 3 cases stained in both MGC and MSC. All 3 cases presented with ulcerations in the mucosa lesion, suggesting that the COX-2 expression is due to the presence of inflammation. This study does not support the involvement of COX-2 in the etiophatogenesis of CGCL. PMID- 22042095 TI - The distribution of IGF2 and IMP3 in osteosarcoma and its relationship with angiogenesis. AB - The aim of this study was to investigate the expression patterns of IGF2 and IMP3 in osteosarcoma as well as its relationship with angiogenesis in the tumor. IGF2 and IMP3 expression was detected by immunohistochemical staining in the serial sections of the osteosarcoma. The impacts of IGF2 and IMP3 expression patterns on tumor angiogenesis were evaluated by statistics. The IGF2 and IMP3 staining had different expression patterns in different osteosarcoma. Twelve out of the sixty four cases of conventional osteosarcoma showed nuclear staining patterns, and twenty-nine showed cytoplasmic staining of IGF2 and IMP3 simultaneously. On the other hand, fourteen cases showed nuclear IGF2 staining but cytoplasmic IMP3 expression, and nine cases showed nuclear IMP3 staining and cytoplasmic IGF2 expression. Twenty-eight out of forty-seven cases of parosteal osteosarcoma showed nuclear IGF2 and IMP3 expression, nine showed cytoplasmic IGF2 and IMP3 expression simultaneously. Seven out of forty-seven cases of parosteal osteosarcoma expressed IGF2 with nuclear staining but expressed IMP3 with cytoplasmic staining. Meanwhile, three cases expressed IGF2 with cytoplasmic staining but expressed IMP3 with nuclear staining. Similar to the parosteal osteosarcoma, the periosteal osteosarcoma expressed IGF2 and IMP3 mainly with nuclear staining simultaneously, forty out of fifty-five cases of periosteal osteosarcoma did that. Five out of fifty-five cases expressed IGF2 and IMP3 with cytoplasmic staining at the same time. Four cases showed nuclear IGF2 staining and cytoplasmic IMP3 staining. In the parosteal and periosteal osteosarcoma, there was no significant difference in IGF and IMP3 expression patterns (P = 0.216). However, compared with conventional osteosarcoma, the parosteal and periosteal osteosarcoma showed significant difference in IMP3 and IGF2 expression (P = 0.016, P = 0.023). IGF2 and IMP3 expression patterns were positive correlation in the different osteosarcoma (r = 0.1021, P = 0.032). The Microvessel density (MVD) in osteosarcoma with IGF2 and IMP3 cytoplasmic staining was more than that with nuclear expression of IGF2 and IMP3, and the difference was significant (P = 0.024). Moreover, the conventional osteosarcoma with cytoplasmic IGF and IMP3 showed more MVD than parosteal and periosteal osteosarcoma with cytoplasmic IGF and IMP3, and the difference was significant (P = 0.035). IGF2 and IMP3 had different expression patterns, which might be associated with angiogenesis. However, cytoplasmic and nuclear expression of IGF2 and IMP3 might play different roles in the angiogenesis of osteosarcoma. PMID- 22042096 TI - Interplay between the structural and magnetic probes in the elucidation of the structure of a novel 2D layered [V4O4(OH)2(O2CC6H4CO2)4].DMF. AB - The title compound has been synthesized under solvothermal conditions by reacting vanadium(V) oxytriisopropoxide with terephthalic acid in N,N-dimethylformamide. A combination of synchrotron powder diffraction, infrared spectroscopy, scanning and transmission electron microscopy, and thermal and chemical analysis elucidated the chemical, structural and microstructural features of a new 2D layered inorganic-organic framework. Due to the low-crystallinity of the final material, its crystal structure has been solved from synchrotron X-ray powder diffraction data using a direct space global optimization technique and subsequent constraint Rietveld refinement. [V(4)O(4)(OH)(2)(O(2)CC(6)H(4)CO(2))(4)].DMF crystallizes in the monoclinic system (space group P2/m (No. 10)); cell parameters: a = 20.923(4) A, b = 5.963(4) A, c = 20.425(1) A, beta = 123.70(6) degrees , V = 2120.1(9) A(3), Z = 2. The overall structure can be described as an array of parallel 2D layers running along [-101] direction, consisting of two types of vanadium oxidation states and coordination polyhedra: face-shared trigonal prisms (V(4+)) and distorted corner-shared square pyramids (V(5+)). Both configurations form independent parallel chains oriented along the 2-fold symmetry crystallographic b axis mutually interlinked with terephthalate ligands in a monodentate mode perpendicular to it. The morphology of the compound exhibits long nanofibers, with the growth direction along the layered [-101] axis. The magnetic susceptibility measurements show that the magnetic properties of [V(4)O(4)(OH)(2)(O(2)CC(6)H(4)CO(2))(4)].DMF can be described by a linear antiferromagnetic chain model, with the isotropic exchange interaction of J = -75 K between the nearest V(4+) neighbours of S = 1/2. PMID- 22042097 TI - Behcet's disease and genes within the major histocompatibility complex region. AB - The role of genetic background in the development of Behcet's disease (BD) is best reflected by the strong association between HLA-B*51 and BD that has been demonstrated across various ethnic groups. The contributions made by other HLA or non-HLA genes to disease susceptibility have been suggested by the results of a number of gene association studies, although the true associations between the genes located within the major histocompatibility complex (MHC) region and BD have often been doubted due to the possibility of linkage disequilibrium of those genes with HLA-B*51. The presence of a true susceptibility gene in the vicinity of HLA-B*51 has also been extensively investigated because of the limited evidence that directly relates HLA-B*51 to the pathogenesis of BD. However, recent genome-wide association studies have confirmed that HLA-B*51 is primarily associated with BD and that there are multiple susceptibility loci other than HLA B*51. In this review, we discuss BD-associated genes within the MHC region and their biological roles in the pathogenesis of BD. PMID- 22042098 TI - Antiribosomal-P protein antibodies are associated with proliferative glomerulonephritis more strongly than with membranous glomerulonephritis in Japanese patients with systemic lupus erythematosus. PMID- 22042099 TI - Content of vascular endothelial growth factor in stratum corneum well correlates to local severity of acute inflammation in patients with atopic dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease, characterized by existence of both acute and chronic eczema. Various markers are used to clinically evaluate the severity of AD as a whole. However, little is known regarding markers that can efficiently indicate the severity of a localized lesion. Vascular endothelial growth factor (VEGF), a potent activator of vascular permeability, is known to be increased in AD lesions. In order to establish whether the VEGF content in the stratum corneum (scVEGF) can be used as a marker to evaluate severity of AD lesions, we evaluated the association between scVEGF and symptom scores of localized lesions. METHODS: Fifty patients with AD and 12 healthy subjects were enrolled. Skin lesions were evaluated and transepidermal water loss and skin water content of the lesions were measured. Stratum corneum samples were collected from the skin of back, neck and arm by the tape stripping technique. The scVEGF were evaluated using a VEGF-specific ELISA method after extracting protein from the scales. RESULTS: The scVEGF levels were significantly higher in patients with AD than in healthy controls. Moreover, the scVEGF levels highly correlated with the manifestation scores of erythema and edema/papulation, and weakly correlated with the scores of excoriation, xerosis and itch. They also correlated significantly with transepidermal water loss and skin water content. CONCLUSIONS: The scVEGF levels correlated well with the severity of clinical conditions, especially erythema and edema/papulation. scVEGF level is considered to be a useful marker to evaluate acute inflammatory conditions in individual AD lesions. PMID- 22042101 TI - Liver cirrhosis on the colonic anastomotic healing in rats. AB - PURPOSE: To investigate the effects of cirrhosis on colonic anastomosis healing in rats. METHODS: Fifty five Wistar male rats were used (23 in the control group and 32 in the cirrhosis group). On the first day of the procedure, the rats in the cirrhosis group underwent double ligation and folding of the common bile duct to induce liver cirrhosis, and the control rats underwent a laparotomy and intestinal manipulation. On the fourteenth and thirty-fifth days, all of the animals were biochemically assessed for serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, total protein, and albumin and for liver histopathology. On the thirty-fifth day, cirrhosis was confirmed. On the twenty-eighth day, all of the animals were subjected to left colon transection and anastomosis. On the seventh day after the colonic anastomosis, the rats were sacrificed and macroscopically evaluated for dehiscence. The region of the colonic anastomosis was removed and subjected to hydroxyproline content measurement, conventional histology, and the immunohistochemical determination of vascular endothelial growth factor (VEGF) and matrix metalloproteinase type 1 (MMP 1). RESULTS: The biochemical and histopathological examinations confirmed cirrhosis in all of the animals in the cirrhosis group. More deaths occurred after anastomosis in the cirrhosis group (5/25) than in the control group (0/21), and anastomotic dehiscence was more frequent in the cirrhosis group (8/25) than in the control group (0/21). The average hydroxyproline concentration was lower in the cirrhosis group than in the control group. The immunohistochemical studies showed that the average VEGF expression in the cirrhosis group was lower than in the control group, and the average MMP1 expression was higher in the cirrhosis group. CONCLUSION: Hepatic cirrhosis leads to increased mortality and colonic anastomotic dehiscence, an increased distance between the mucosal edges of the anastomosis area, and a lower hydroxyproline concentration in the colonic anastomosis; therefore, these conditions are deleterious to healing. PMID- 22042102 TI - A new proposal to evaluate the healing of open skin wounds: volumetry. AB - PURPOSE: To present a new proposal to evaluate the healing of an open subcutaneous and skin wound, which we termed "volumetry". METHODS: A total of 32 circular wounds were performed in the subcutaneous tissues and skin of four feet of pigs (8 each). Each wound had about 1 cm in diameter and was 0.2 cm deep. Volume was calculated from the wound filled with saline and mass Xantopren. With the aid of a magnifying glass and local lighting, the liquid was dripped with a micropipette inside the wound until complete fullness. Volume repletion was calculated in microliters, corresponding to the volume of the wound. The mass of Xantopren was placed inside the wound to obtain a mold of the lesion. Mold volume was calculated using the formula of the volume of a cylinder closest resembling a geometric figure with mold. RESULTS: The calculation of wound volume was possible with both Xantopren and mold techniques. Volume as calculated by micropipette was 119.37 +/- 30.87 microliters while the volume calculated by mold was 122.41 +/- 33.90 mm3 (p=0.79). CONCLUSIONS: Volumetry in pig feet is simple and reproducible. Volumetry perfomed with saline did not differ from the volumetry with mass Xantopren. This method may be a useful tool to help evaluate the healing of open skin wounds in experimental and clinical research. PMID- 22042103 TI - The use of Portland cement in the repair of mandibular fractures in rats. AB - PURPOSE: To evaluate the bone healing of mandibular fractures following the use of Portland cement. METHODS: Thirty-two male Wistar rats were divided into control and experimental groups. In the control group the rats were submitted to a mandibular fracture, which was reduced, and the soft tissues were sutured. In the experimental group the rats had the mandibular fracture reduced and maintained with the Portland cement. The animals were euthanized 7 and 21 days after surgery by injecting a lethal dose of anesthetic. The following variables were studied: weight of the animals, radiographic images, histopathological features and time of surgery. RESULTS: A weight loss was observed in the specimens of both groups at the different times of evaluation, a greater difference in weight before and after surgery being found in the experimental group, which was statistically significant (p <0.05, p = 0.041). From the histological point of view, with a margin of error (5.0%) the only two significant differences (p <0.05) recorded in the variables were "Material deployed" and "Bone resorption" during the evaluations at 7 and 21 days, respectively. CONCLUSION: The Portland cement served to promote bone healing. PMID- 22042104 TI - Effects of bromopride on abdominal wall healing with induced peritoneal sepsis after segmental colectomy and colonic anastomosis in rats. AB - PURPOSE: Evaluate the effects of bromopride on abdominal wall healing of rats with induced peritoneal sepsis after segmental colectomy and colonic anastomosis. METHODS: Forty rats underwent sectioning of the left colon and end-to-end anastomosis and were divided into two groups of 20 animals for the administration of bromopride (bromopride group - B) or saline solution (control group - C). Each group was divided into subgroups of 10 animals each to be killed on the third (GB3 and GC3) or seventh postoperative day (GB7 and GC7). It was analyzed the following characteristics: breaking strength of the abdominal wall's wound; surgical and histopathological features of the abdominal wall; and clinical features of the rats. RESULTS: There was no difference between the groups in relation to the weight of the rats and the breaking strength of the abdominal wall's wound. The GB7 group presented less edema and less quantity of fibrin during histopathological evaluation compared to the GC7 group. CONCLUSION: Bromopride did not have harmful effects on the healing of abdominal wall in rats. PMID- 22042105 TI - Pretreatment with pentoxifylline attenuates lung injury induced by intestinal ischemia/reperfusion in rats. AB - PURPOSE: To investigate the protective effect of pentoxifylline against the lung injury observed after intestinal ischemia (I) followed by a period of reperfusion (R). METHODS: Twenty-eight male Wistar rats were equally divided into 4 experimental groups and operated under ketamine-xylazine anesthesia. (1) Sham: falsely-operated animals; (2) SS+IR: intestinal ischemia was accomplished by clipping the superior mesenteric artery during 60 minutes, with an administration of a standard volume of saline solution (SS) 5 min before the end of the ischemia period; the clip was then releases or a 120-min period of reperfusion; (3) I+PTX+R: ischemia as above, PTX was administered (25 mg/kg) and the gut reperfused as above; (4) PTX+I+PTX+R: Five minutes before arterial occlusion PTX was administered; the superior mesenteric artery was then clipped for 60 minutes. After 55-min ischemia, an additional dosis of PTX was administered; the clip was removed for reperfusion as above. At the 60th min of reperfusion a third dosis of PTX was administered. RESULTS: PTX markedly attenuated lung injury as manifested by significant decreases (all P<0.001 as compared with the SS+IR group) of pulmonary wet/dry tissue weight ratio, total protein content, myeloperoxidase activity and tumor necrosis factor-alpha. Moreover, it was apparent that in the group PTX+I+PTX+R the improvements have been even more significant. CONCLUSION: PTX exerted a protective effect on the lung from the injuries caused by intestinal ischemia/reperfusion. PMID- 22042107 TI - Histological analysis and the blood flux in kidneys submitted to different periods of ischemia/reperfusion. AB - PURPOSE: Evaluate the renal blood flow by using a laser flow meter, Laserflow Vasamedics(r), after the ischemia/reperfusion in two different times of the arterial renal vessel clamping. METHODS: The renal blood flow was evaluated by using a laser flow meter after two different times of ischemia/reperfusion procedure, 30 and 60 minutes. It was used 20 Wistar male rats, divided in two groups of 10 rats: Group A (30 minutes of ischemia on the left kidney, with later analysis of the blood flow in 1, 5 and 20, after the renal reperfusion start) and Group B (60 minutes of ischemia on the left kidney, with later analysis of the blood flow in 1, 5 and 20 minutes, after the renal reperfusion start). RESULTS: In the first minute, there were not significant differences between the two groups (p=0.789). In the 5th minute there were not significant differences also, but there was a tendency (p=0.068). In the 20th minute, there was a significant difference between the 2 groups (p=0.022). When the means are observed, it is possible to notice that Group A has a larger flux than Group B. CONCLUSION: The kidneys submitted to 30' of ischemia/reperfusion are subject to a larger restitution of the blood flow in comparison to the Group which had a longer time. PMID- 22042106 TI - Effect of glutamine on the total antioxidant system of rats subjected to renal ischemia and reperfusion. AB - PURPOSE: To evaluate the protective effects of glutamine administered before renal ischemia-reperfusion on plasma antioxidant protection, and lung and renal tissue injury. METHODS: 33 rats underwent right nephrectomy. On the eighth postoperative day, animals were randomized into three groups (n=11): glutamine, control and sham. Each group of animals received, by gavage, a particular diet for 7 days. On day 14 following nephrectomy, the animals were subjected to left renal ischemia-reperfusion. After this, blood samples were collected and the animals were killed. At necropsy the kidney and lung were removed for histology. RESULTS: The levels of total antioxidant capacity were higher in the glutamine group and control group compared with the sham group. The levels of glutathione peroxidase in both the sham and glutamine groups were higher when compared with the control group (p<0.05). The level of superoxide dismutase in the sham group was clearly higher than that in the glutamine and control groups. Histological examination showed no differences between the three groups. CONCLUSION: Prior intake of glutamine improves total antioxidant capacity and increases glutathione peroxidase levels in rats subjected to renal ischemia-reperfusion. PMID- 22042108 TI - Protective perioperative strategy using a third generation hydroxyethyl starch during surgery in a murine model of liver reperfusion injury. AB - PURPOSE: To investigate whether a third generation colloid, hydroxyethyl starch (HES 130/0.4), used for perioperative fluid therapy, protects the rat liver against the late-phase response of ischemia/reperfusion injury (IRI) and if inhibition of neutrophil hepatic infiltration plays a part in this mechanism. METHODS: Wistar rats were used (8 in each group). Three groups had IRI induced by lobar vascular occlusion (60 minutes) and reperfusion (24 hours) and received HES (13 mL/kg iv), 7.5% saline (HS) (13 mL/kg iv) or no fluid. Three other groups were sham-operated and received the same fluid as the test groups. After 24 hours of reperfusion, blood was drawn for alanine aminotransferase (ALT) quantification and ischemic liver samples were taken for histological study (hematoxylin and eosin and chloroacetate staining of neutrophils). RESULTS: HES treatment attenuated the elevation in serum ALT (P=0.001) and reduced the extent of hepatocellular necrosis (P<0.01) compared with the IRI controls. HES-mediated cytoprotection was associated with a decrease of infiltration of neutrophils in the necrotic areas (P<0.05) compared with the untreated IRI rats, but not with the volume control IRI rats (P>0.05). CONCLUSION: Hydroxyethyl starch suppresses inflammatory response and ameliorates the late-phase response of hepatic ischemia/reperfusion injury. PMID- 22042109 TI - Effect of hyperbaric oxygen therapy on the intestinal ischemia reperfusion injury. AB - PURPOSE: Adequate tissue oxygenation is essential for healing. Hyperbaric oxygen therapy (HBOT) has potential clinical applications to treat ischemic pathologies, however the exact nature of any protective effects are unclear at present. We therefore investigated the potential role of HBOT in modulating the ischemia/reperfusion (I/R) injury response in intestinal model of I/R injury. METHODS: Male Wistar rats were subjected to surgery for the induction of intestinal ischemia followed by reperfusion. HBOT was provided before and/or after intestinal ischemia. Cell viability in the intestinal tissue was assessed using the MTT assay and by measuring serum malondealdehyde (MDA). Microvascular density and apoptosis were evaluated by immunohistochemistry. RESULTS: The results indicate that HBOT treatment pre- and post-ischemia reduces lesion size to the intestinal tissue. This treatment increases cell viability and reduces the activation of caspase-3, which is associated with increased number of tissue CD34 cells and enhanced VEGF expression. CONCLUSION: The hyperbaric oxygen therapy can limit tissue damage due to ischemia/reperfusion injury, by inducing reparative signaling pathways. PMID- 22042110 TI - Effect of laser on the remnant liver after the first 24 hours following 70% hepatectomy in rats. AB - PURPOSE: To evaluate the mitochondrial function of the remnant liver (RL) in the early phase of liver regeneration in rats after 70% partial hepatectomy (PH). METHODS: Sixty male Wistar rats (200-250g) submitted to 70% PH were divided into five groups according to the time of euthanasia and application or not of laser light: C = Control, time zero; 2 minutes, 4, 6 and 24 hours after PH. The dose of laser radiation was 22.5 J/cm(2), wavelength of 660 nm (visible/red), in the remnant liver. We studied the respiration activated by ADP (state 3), basal mitochondrial respiration (state 4), respiratory control ratio (RCR) and mitochondrial membrane potential (MMP). RESULTS: The mitochondrial function of RL changed at 4 and 6 hours after PH, with a significant increase in state 3 and a concomitant increase in state 4 and with maintenance of RCR. MMP differed significantly between the groups biostimulated with laser radiation and the control group 4 hours after HP, with a substantial reduction in the non-laser groups. CONCLUSION: The laser light at the dose used in this study did not induce additional damage to the RL and seems to have delayed the hepatocellular metabolic overload of the remnant liver. PMID- 22042111 TI - Effects of ionizing radiation on bone neoformation: histometric study in Wistar rats tibiae. AB - PURPOSE: Comparing the ionizing radiation effects on bone neoformation of rats tibiae previously submitted to radiotherapy with a single dosage of 30Gy with the contralateral tibiae that have received secondary radiation. METHODS: In thirty male Wistar rats, 30 days before surgical procedure when round defects would be created on the bone, the right tibia was irradiated with 30Gy and the left tibia received a calculated secondary radiation dose of 7Gy. Sacrifices were performed after 4, 7, 14, 21, 56 and 84 postoperative days and both tibiae were removed for histological processing. RESULTS: The left tibiae that received the dose of 7Gy has shown more bone neoformation from 14(th) postoperative days, giving evidences of less damage to cellular population responsible by bone neoformation. On the other hand, the dose of 30Gyon right tibiae did not exhibit significant differences among the periods, suggesting damage of long-lasting or even permanent duration. CONCLUSION: Tibiae submitted to radiation dose of 30Gy have shown more damage to bone cells than tibiae that received secondary radiation dose of 7Gy, especially observed on 14(th), 56(th) and 84(th) postoperative days. PMID- 22042112 TI - Methylene blue administration in the compound 48/80-induced anaphylactic shock: hemodynamic study in pigs. AB - PURPOSE: To verify if the methylene blue (MB) administration prevents and/or reverses the compound 48/80 (C48/80)-induced anaphylactic shock in pigs. METHODS: Female Dalland pigs were anesthetized and had the hemodynamic parameters recorded during the necessary time to administer some drugs and observe their effect. The animals were randomly assigned to one of the five groups: 1) control; 2) MB: the animals received a bolus injection of MB (2 mg/kg) followed by continuous infusion of MB (2.66 mg/Kg/h delivered by syringe infusion pump); 3) C48/80: the animals received a bolus injection of C48/80 (4 mg/kg); 4) C48/80+MB: the animals received a bolus injection of C48/80 (4 mg/kg) and 10 minutes after the C48/80 administration the animals received a bolus injection of MB (2 mg/kg) followed by continuous infusion of MB (2.66 mg/Kg/h delivered by syringe infusion pump); 5) MB+C48/80: the animals received a bolus injection of MB (2 mg/kg) and 3 minutes later they received a bolus injection of C48/80 (4 mg/kg). RESULTS: The intravenous infusion of MB alone caused no changes in the mean arterial pressure (MAP) showing that the administered MB dose was safe in this experimental model. The C48/80 was effective in producing experimental anaphylactic shock since it was observed a decrease in both MAP and cardiac output (CO) after its administration. The MB did not prevent or reverse the C48/80-induced anaphylactic shock in this model. In fact, the MAP of the animals with anaphylactic shock treated with MB decreased even more than the MAP of the animals from the C48/80 group. On the other hand, the C48/80-induced epidermal alterations disappeared after the MB infusion. CONCLUSION: Despite our data, the clinical manifestations improvement brings some optimism and does not allow excluding the MB as a possible therapeutic option in the anaphylactic shock. PMID- 22042113 TI - Assessment of gait dynamics in rats submitted to limb ischemia. AB - PURPOSE: To describe a method for the assessment of gait dynamics in rats submitted to limb ischemia. METHODS: Twenty-four male Wistar rats (150-160g) were used. Twelve animals were submitted to limb ischemia by ligation of the common left iliac artery (ischemic group: n = 12); and a sham-operated group was used as control (n=12). After a recovery period of 6 weeks, gait dynamics was assessed by counting the complete footprints and the number of hindlimb-floor contacts during a treadmill test for five minutes at a speed of 12 m.min(-1) and angulation of 15 degrees . The number of contacts of the left hindlimb was divided by the right hindlimb values (LRR) for group comparisons. Ischemic disability was quantified by comparing the area under curve (AUC) created by plotting each contact versus time for each hindlimb. The left hindlimb ischemic disability index (LHDI), which was compared between groups, was defined by the formula: LHDI = (1- AUC (left) / AUC (right)) x 100. RESULTS: Surgery was well tolerated by all animals. Rats did not suffer tissue loss or ulcerations. Complete footprint LRR was 0.3 +/- 0.08 for the ischemic group and 1.3 +/- 0.9 for controls (p=0.0043). Number of contacts LLR was 0.5 +/- 0.2 for the ischemic group and 1.0 +/- 0.1 for the control group (p=0.0051). LHDI was 56.83 +/- 10.67 for the ischemic group and 2.50 +/- 13.10 for the control group (P = 0.031). CONCLUSION: Assessment of gait dynamics in rats submitted to limb ischemia could be done by footprint analysis and hindlimb contact recording during a treadmill test. PMID- 22042114 TI - Small bowel transplantation in outbred rats. AB - PURPOSE: To investigate the clinical evolution of orthotopic small bowel transplantation in outbred rats. METHODS: Seventy-two outbred Wistar rats weighting from 250 to 300g were used as donor and recipient in 36 consecutives ortothopic small intestine transplantation without immunosuppression. The graft was transplanted into the recipient using end-to-side aortic and portacaval microvascular anastomosis. Procedure duration, animal clinical course and survival were evaluated. Survival shorter than four days was considered technical failure. Recipients were sacrificed with signs of severe graft rejection or survival longer than 120 days. Necropsies were performed in all recipients to access histopathological changes in the graft. RESULTS: Median time for the procedure was 107 minutes. Six recipients (16.7%) presented technical failure. Twenty-seven recipients were sacrificed due to rejection, being nineteen (52.7%) between 7(th) and 15(th) postoperative day and eight (22.2%) between 34(th) and 47(th) postoperative day. Graft histology confirmed severe acute cellular rejection in those recipients. Uneventful evolution and survival longer than 120 days without rejection were observed in three recipients (8.3%). CONCLUSION: Intestinal transplantation in outbred rats without immunosuppressant regiment accomplishes variable clinical evolution. PMID- 22042115 TI - Metabolic and hematologic consequences of colectomy associated to hepatectomy in rats. AB - PURPOSE: To investigate the influence of partial colectomy associated with hepatectomy on the biodistribution of the (99m)Tc-phytate, on metabolic parameters, as well as labeling and morphology of red blood cells. METHODS: Wistar rats were distributed into three groups (each with six), nominated as colectomy, colectomy+hepatectomy and sham. In the 30(th) postoperative day all rats were injected with (99m)Tc-phytate 0.1mL i.v. (radioactivity 0.66 MBq). After 15 minutes, liver sample was harvested and weighed. Percentage radioactivity per gram of tissue (%ATI/g) was determined using an automatic gamma counter. Serum AST, ALT, alkaline phosphatase and red blood cells labeling were determined. RESULTS: The liver %ATI/g and red blood cells labeling were lower in colectomy and colectomy+hepatectomy rats than in sham rats (p <0.05), and no difference was detected comparing the colectomy and colectomy+hepatectomy groups. Red blood cells morphology did not differ among groups. Serum levels of AST, ALT and alkaline fosfatase were significantly higher in colectomy+hepatectomy than in colectomy rats (p<0.001). CONCLUSION: Hepatectomy associated with colectomy lowered the uptake of radiopharmaceutical in liver and in red blood cells in rats, coinciding with changes in liver enzymatic activity. PMID- 22042116 TI - Intrapleural analgesia after endoscopic thoracic sympathectomy. AB - PURPOSE: To compare analgesia traditionally used for thoracic sympathectomy to intrapleural ropivacaine injection in two different doses. METHODS: Twenty-four patients were divided into three similar groups, and all of them received intravenous dipyrone. Group A received intravenous tramadol and intrapleural injection of saline solution. Group B received intrapleural injection of 0.33% ropivacaine, and Group C 0.5% ropivacaine. The following aspects were analyzed: inspiratory capacity, respiratory rate and pain. Pain was evaluated in the immediate postoperative period by means of the visual analog scale and over a one week period. RESULTS: In Groups A and B, reduced inspiratory capacity was observed in the postoperative period. In the first postoperative 12 hours, only 12.5% of the patients in Groups B and C showed intense pain as compared to 25% in Group A. In the subsequent week, only one patient in Group A showed mild pain while the remainder reported intense pain. In Group B, half of the patients showed intense pain, and in Group C, only one presented intense pain. CONCLUSION: Intrapleural analgesia with ropivacaine resulted in less pain in the late postoperative period with better analgesic outcomes in higher doses, providing a better ventilatory pattern. PMID- 22042117 TI - Can Wistar rats be used as the normotensive controls for nerve morphometry investigations in spontaneously hypertensive rats (SHR)? AB - PURPOSE: We compared the sural nerve morphology among Wistar (WR), Wistar-Kyoto (WKY) and Spontaneously hypertensive (SHR) rats, including the nerve fascicles and myelinated fibers morphometry. METHODS: Age matched (20 weeks) female WR (N=6), WKY (N=6) and SHR (N=7) had their right and left sural nerves removed, embedded in epoxy resin, and observed by light microscopy. Morphometric analysis was performed with the aid of computer software. RESULTS: Despite presenting the same age, WR were heavier than WKY and SHR, as were SHR compared to WKY. Systolic arterial pressure was higher in SHR compared to WR, but no differences between SHR and WKY or WR and WKY were observed. The sural nerves were morphometrically symmetric between proximal and distal segments on the same side and between sides in all strains with no differences in the myelinated fiber number. Schwann cell number and density were smaller in SHR and G ratio was larger in SHR, indicating that SHR have thinner myelinated fibers. CONCLUSION: Sural nerve morphology is similar between WKY and WR, allowing the use of WR as the SHR controls in morphological investigations involving peripheral neuropathies. PMID- 22042118 TI - Morphometric analysis of dendritic cells from anal mucosa of HIV-positive patients and the relation to intraepithelial lesions and cancer seen at a tertiary health institution in Brazil. AB - PURPOSE: To morphometrically quantify CD1a+ dentritic cells and DC-SIGN+ dendritic cells in HIV-positive patients with anal squamous intraepithelial neoplasia and to evaluate the effects of HIV infection, antiretroviral therapy and HPV infection on epithelial and subepithelial dendritic cells. METHODS: A prospective study was performed to morphometrically analyze the relative volume of the dendritic cells and the relationship between anal intraepithelial neoplasia and cancer in HIV-positive patients from the Tropical Medicine Foundation of Amazonas, Brazil. All patients were submitted to biopsies of anorectal mucosa to perform a classic histopathological and immunohistochemical analysis, employing antibodies against CD1a and DC-SIGN for the morphometric quantification of dendritic cells. RESULTS: HIV-negative patients displayed a CD1a DC density significantly higher than that of HIV-positives patients (3.75 versus 2.54) (p=0.018), and in patients with severe anal intraepithelial neoplasia had correlated between DC CD1a density with levels of CD4 + cells (p: 0.04) as well as the viral load of HIV-1 (p: 0.035). A not significant rise in the median density of CD1a+ DC was observed in the HIV positive/ HAART positive subgroup compared to the HIV positive/ HAART negative subgroup. The CD1a+ DC were also significantly increased in HIV-negative patients with anorectal condyloma (2.33 to 3.53; p=0.05), with an opposite effect in HIV-positive patients. CONCLUSIONS: Our data support an enhancement of the synergistic action caused by HIV-HPV co-infection on the anal epithelium, weakening the DC for its major role in immune surveillance. Notoriously in patients with severe anal intraepithelial neoplasia, the density of CD1a+ epithelial dendritic cells was influenced by the viral load of HIV-1. Our study describes for the first time the density of subepithelial DC-SIGN+ dendritic cells in patients with anal severe anal intraepithelial neoplasia and points to the possibility that a specific therapy for HIV induces the recovery of the density of epithelial DC. PMID- 22042119 TI - Analysis of 83 consecutive liver transplants performed at a tertiary care reference hospital in the interior of the state of Sao Paulo. AB - PURPOSE: To analyze pre-, intra- and immediate postoperative parameters of patients submitted to liver transplantation. METHODS: Eighty-three consecutive orthotopic liver transplants performed from January 2009 to July 2011 were analyzed. The patients were divided into 2 groups: A, survivors (MELD between 9 and 60) and B, non-survivors (MELD between 14 and 40), with 30.6% of group A patients being CHILD C, 51c/o CHILD B and 18,4c/o CHILD A. In group B, 32.1c/o of the patients were CHILD C, 42,9c/o CHILD B, and 25c/o CHILD A. All orthotopic liver transplantations were performed using the piggyback technique without a portacaval shunt. Systemic arterial pressure and serum ALT and AST levels were determined preoperatively and 5, 60 and 1440 minutes after arterial graft revascularization. Serum ALT and AST profiles were evaluated for seven days after surgery. RESULTS: Systemic arterial blood pressure levels, time of hot and hypothermic ischemia and time of graft implant were statistically similar for the two groups (p>0.05). Serum levels (U/L) of ALT and AST at the 5, 60 and 1440 minute time points after arterial revascularization of the graft were also similar for the two groups studied, as also were the serum ALT and AST profiles. CONCLUSIONS: No statistically significant difference in any of the parameters studied was detected between the two groups. Under the conditions of the present study and on the basis of the parameters evaluated, no direct relation was detected between the intraoperative period and the type of patient outcome in the two groups studied. PMID- 22042120 TI - The use of perioperative serial blood lactate levels, the APACHE II and the postoperative MELD as predictors of early mortality after liver transplantation. AB - PURPOSE: To evaluate the accuracy of different parameters in predicting early (one-month) mortality of patients submitted to orthotopic liver transplantation (OLT). METHODS: This is a retrospective study of forty-four patients (38 males and 10 females, mean age of 52.2 +/- 8.9 years) admitted to the Intensive Care Unit of a tertiary hospital. Serial lactate blood levels, APACHE II, MELD post OLT, creatinine, bilirubin and INR parameters were analyzed by receiver-operator characteristic (ROC) curves as evidenced by the area under the curve (AUC). The level of significance was set at 0.05. RESULTS: The mortality of OLT patients within one month was 17.3%. Differences in blood lactate levels became statistically significant between survivors and nonsurvivors at the end of the surgery (p<0.05). The AUC was 0.726 (95%CI = 0.593-0.835) for APACHE II (p = 0.02); 0.770 (95%CI = 0.596-0.849) for blood lactate levels (L7-L8) (p = 0.03); 0.814 (95%CI = 0.690-0.904) for MELD post-OLT (p < 0.01); 0.550 (95%CI = 0.414 0.651) for creatinine (p = 0.64); 0.705 (95%CI = 0.571-0.818) for bilirubin (p = 0.05) and 0.774 (95%CI = 0.654-0.873) for INR (p = 0.02). CONCLUSION: Among the studied parameters, MELD post-OLT was more effective in predicting early mortality after OLT. PMID- 22042121 TI - Perioperative care in an animal model for training in abdominal surgery: is it necessary a preoperative fasting? AB - PURPOSE: Demonstrate that the rabbit may be used in the training of surgery, in addition to present its perioperative care. METHODS: Thirty two animals, with age and weight, respectively, from 3 to 5.5 months old and 3000 to 4200 grams, were undergone different periods of pre-operative fasting, exclusive intramuscular anesthesia (ketamine+xylazine), laparotomy with total gastrectomy and total splenectomy. It was dosed the pre-operative (initial) and post-surgical (end) serum blood glucose, in addition to quantify the gastric content after the resection of the part. RESULTS: The anesthetical-surgical procedure presented a mortality rate of 3.125% (1:32) and a morbidity rate of 6.25% (2:32). It was evidenced an initial mean blood glucose = 199.4 mg/dl and the end = 326.1 mg/dl. In spite of extended fasting (minimum of 2 hours for the absolute fasting and maximum of 8.5 hours for liquids, and 20.5 hours for solids) all animals presented at the end of the surgical procedure any gastric content and a blood glucose increase. Those with fasting for liquids and solids when compared to the quantity of solid gastric content, presented a moderate negative degree of correlation. CONCLUSION: The rabbit is a good model to be used in training of surgery, with a low morbi-mortality, able to be anesthetized intramuscularly, with no need of pre-operative fasting and does not present hypoglycemia even with the extended fasting period. PMID- 22042122 TI - Assessing the placement of a cochlear electrode array by multidimensional scaling. AB - Correct placement of the electrode is crucial for cochlear implantation (CI) surgery. It determines the access to the auditory nerve and subsequent hearing performance. Here, we propose an objective measures tool that can partially verify the electrode position. The intracochlear spread of the electrical fields is measured and analyzed by means of multidimensional scaling resulting in an intuitive visual representation. The user can then detect major issues, such as electrode foldover or ossification. Other implantation issues, such as electrode migration into the scala vestibuli, may not significantly alter the electrical conduction pattern and remain undetected. Still, as the measurement is quick and readily available, it may be a valuable intraoperative verification tool. PMID- 22042123 TI - Multiscale mathematical modeling to support drug development. AB - It is widely recognized that major improvements are required in the methods currently being used to develop new therapeutic drugs. The time from initial target identification to commercialization can be 10-14 years and incur a cost in the hundreds of millions of dollars. Even after substantial investment, only 30 40% of the candidate compounds entering clinical trials are successful. We propose that multiscale mathematical pathway modeling can be used to decrease time required to bring candidate drugs to clinical trial and increase the probability that they will be successful in humans. The requirements for multiple time scales and spatial scales are discussed, and new computational paradigms are identified to address the increased complexity of modeling. PMID- 22042124 TI - Stochastic modeling of the relationship between copy number and gene expression based on transcriptional logic. AB - DNA copy number alterations (CNAs) can cause genetic diseases, and studies have revealed a relationship between CNAs and gene expression; however, the manner in which CNAs relate to gene expression and what regulatory mechanisms underlying the relationship remain unclear. In many instances, real data have revealed a nonlinear relationship between copy number and gene expression. In this paper, queueing theory is used to model this relationship, with the basic structural parameters involving transcription factor (TF) arrival and departure rates. A key finding is that the ratio of TF arrival rate to TF departure rate is critical: small and large ratios corresponding to nonlinear and linear relationships, respectively. Indeed, copy number amplifications do not necessarily lead to expression increases: when one of the regulatory TFs exists in a small amount, copy number gains can cause a down regulation. Using the concept of mutual information, we show that the TF with minimum activation probability can have maximum dependence in regulation: a TF in small amount could result in a nonlinear copy-number-gene-expression relationship and play a major role in regulation. The expectation-maximization algorithm is used to estimate the ratio of TF arrival rate to TF departure rate. The theoretical results are illustrated via simulations. PMID- 22042125 TI - A miniature vibrotactile sensory substitution device for multifingered hand prosthetics. AB - A multisite, vibrotactile sensory substitution system, that could be used in conjunction with artificial touch sensors in multifingered prostheses, to deliver sensory feedback to upper limb amputees is presented. The system is based on a low cost/power/size smart architecture of off-the-shelf miniaturized vibration motors; the main novelty is that it is able to generate stimuli where both vibration amplitude and frequency as well as beat interference can be modulated. This paper is aimed at evaluating this system by investigating the capability of healthy volunteers to perceive-on their forearms-vibrations with different amplitudes and/or frequencies. In addition, the ability of subjects in spatially discriminating stimulations on three forearm sites and recognizing six different combinations of stimulations was also addressed. Results demonstrate that subjects were able to discriminate different force amplitudes exerted by the device (accuracies greater than 75%); when both amplitude and frequency were simultaneously varied, the pure discrimination of amplitude/frequency variation was affected by the variation of the other. Subjects were also able to discriminate with an accuracy of 93% three different sites and with an accuracy of 78% six different stimulation patterns. PMID- 22042126 TI - Implantable polyimide cable for multichannel high-data-rate neural recording microsystems. AB - To avoid or minimize postimplantation injury as a result of brain micromotion relative to the skull, a flexible multichannel polyimide (PI) cable was designed and microfabricated for data and power transmission between an intracranial IC recording from a neural probe array and an extracranial IC exchanging power and data wirelessly with an external unit. Surface characteristics, electrical properties, and cytocompatibility of the PI ribbon cable were investigated in this study. Scanning electron microscopic examination and atomic force microscopy analyses showed that the surface of the PI ribbon cable became significantly rougher due to the reactive oxygen ion etching process to open bonding pads. The enhanced surface roughness was also responsible for the increase in wettability and water absorption rate. However, water permeability measurement revealed that the micromachining fabrication process did not meaningfully affect the acceptable water vapor transmission rate of PI. Moreover, electrical properties, such as insertion loss, isolation between channels and data transmission capacity, were assessed for each channel of the PI ribbon cable on the basis of scattering parameter (S-parameter) measurement. Finally, 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide assay and live/dead intracellular staining tests were carried out to evaluate cell behaviors on the PI ribbon cable, indicating that the PI ribbon cable did not have acute cytotoxicity and appeared to be as cytocompatible as blank PI foils. PMID- 22042127 TI - Switchable Faraday shielding with application to reducing the pain of internal cardiac defibrillation while permitting external defibrillation. AB - Switchable Faraday shielding is desirable in situations where electric field shielding is required at certain times and undesirable at other times. In this study, electrostatic finite element modeling was used to assess the effect of different shield geometries on the leakage of an internally applied field and penetration of an externally applied field. "Switching OFF" the shield by electrically disconnecting shield faces from each other was shown to significantly increase external field penetration. Applying this model to defibrillation, we looked at the effect of spacing and size of shield panels to maximize the ability to deliver an external defibrillation shock to the heart when shield panels are disconnected while providing acceptably low leakage of internal defibrillation shocks to avoid painful skeletal muscle capture when shield panels are connected. This analysis may be useful for designing internal defibrillator electrodes that preserve the efficacy of internal and external defibrillation while avoiding the significant morbidity associated with painful defibrillator shocks. Similar analysis could also guide optimizing the switchable Faraday shielding concept for other applications. PMID- 22042128 TI - Herbivore- and elicitor-induced resistance in groundnut to Asian armyworm, Spodoptera litura (Fab.) (Lepidoptera: Noctuidae). AB - Induced defense was studied in three groundnut genotypes ICGV 86699 (resistant), NCAc 343 (resistant) and TMV 2 (susceptible) in response to Spodoptera litura infestation and jasmonic acid (JA) application. The activity of the oxidative enzymes [peroxidase (POD) and polyphenol oxidase (PPO)] and the amounts other host plant defense components [total phenols, hydrogen peroxide (H2O2), malondialdehyde (MDA), and protein content] were recorded at 24, 48, 72 and 96 h in JA pretreated (one day before) plants and infested with S. litura, and JA application and simultaneous infestation with S. litura to understand the defense response of groundnut genotypes against S. litura damage. Data on plant damage, larval survival and larval weights were also recorded. There was a rapid increase in the activities of POD and PPO and in the quantities of total phenols, H2O2, MDA and protein content in the JA pretreated + S. litura infested plants. All the three genotypes showed quick response to JA application and S. litura infestation by increasing the defensive compounds. Among all the genotypes, higher induction was recorded in ICGV 86699 in most of the parameters. Reduced plant damage, low larval survival and larval weights were observed in JA pretreated plants. It suggests that pretreatment with elicitors, such as JA could provide more opportunity for plant defense against herbivores. PMID- 22042129 TI - Serum levels of bone resorption markers are decreased in patients with type 2 diabetes. AB - Previous studies of bone turnover markers in diabetes are limited, and the results are conflicting. Our aim was to evaluate differences in bone turnover markers and i-PTH between T2DM and non-diabetes subjects. Cross-sectional study including 133 subjects (78 T2DM, 55 without diabetes). BMD were measured by dual X-ray absorptiometry. Bone turnover markers were determined in serum. Serum levels of bone resorption markers (CTX and TRAP5b) were lower in T2DM compared with non-diabetes subjects. There were no differences in bone formation markers. i-PTH serum levels were lower in T2DM: 38.35 +/- 18.20 pg/ml versus 50.22 +/- 18.99 pg/ml, P < 0.05. TRAP5b and CTX were positively correlated with i-PTH (CTX: r = 0.443, P < 0.001; TRAP5b: r = 0.180, P = 0.047). There was an inverse relationship between TRAP5b levels and diabetes duration (r = -0.269, P = 0.021). T2DM patients have lower levels of bone resorption markers, and i-PTH compared with subjects without diabetes. Lower levels of PTH may induce a low turnover state as reflected by lower levels of bone resorption markers, and this situation may influence the higher risk of fracture of T2DM. PMID- 22042130 TI - Angiotensin-(1-7) suppresses oxidative stress and improves glucose uptake via Mas receptor in adipocytes. AB - Although reactive oxygen species (ROS) contribute to glucose intolerance induced by the renin-angiotensin system (RAS) is well documented, the role of the newly discovered pathway of RAS, angiotensin (Ang)-(1-7)/Mas axis, in this process remains unknown. Here, we examined the effect of Ang-(1-7) on oxidative stress and glucose uptake in adipocytes. We used primary cultured epididymal adipocytes from C57 mice to study Ang-(1-7) effects on glucose uptake. We also treated fully differentiated 3T3-L1 adipocytes with exogenous Ang-(1-7) or overexpression of angiotensin-converting enzyme 2 (ACE2) to induce endogenous generation of Ang-(1 7) to clarify its effects on ROS production. Intracellular ROS was measured by flow cytometry, dihydroethidium (DHE), and nitroblue tetrazolium assay. Levels of NADPH oxidase and adiponectin mRNA were measured by real-time PCR. Ang-(1-7) improved glucose uptake both in basal and insulin-stimulated states. ROS production was slightly but significantly decreased in adipocytes treated with Ang-(1-7). Additionally, Mas receptor antagonist D-Ala7-Ang-(1-7) (A779) reversed the effect of Ang-(1-7) on glucose uptake and oxidative stress. Furthermore, treatment of adipocytes with Ang-(1-7) decreased NADPH oxidase mRNA levels. We also found that oxidative stress induced by glucose oxidase-suppressed expression of adiponectin, an insulin-sensitive protein. However, the suppression of oxidative stress by Ang-(1-7) restored adiponectin expression, while A779 agonists these changes induced by Ang-(1-7). In conclusion, Ang-(1-7) can protect against oxidative stress and improve glucose metabolism in adipocytes. These results show that Ang-(1-7) is a novel target for the improvement of glucose metabolism by preventing oxidative stress. PMID- 22042131 TI - Structural damage in diabetic nephropathy is associated with TNF-alpha system activity. AB - In experimental animal studies, tumour necrosis factor-alpha (TNF-alpha) contributed to renal hypertrophy during diabetes, and antibodies against TNF alpha have led to improved histological lesions in animals with nephrotoxicity and diabetic nephropathy. We aimed to evaluate TNF-alpha system activity in association with renal histology in patients with type 2 diabetes. This is a prospective, cross-sectional study of 22 patients with type 2 diabetes (16 men), 13 with microalbuminuria and 9 with normoalbuminuria. Plasma-soluble TNF-alpha receptor 1 and 2 (sTNFR1 and sTNFR2) concentrations were used as surrogates of TNF-alpha system activity. Glomerular filtration rate (GFR) was analysed using I(125)-Iodothalamine. Albumin excretion rate (AER) and a renal biopsy were performed in all subjects. AER did not associate significantly with mesangial expansion or interstitial fraction in these subjects (r < 0.12, P > 0.5). AER was also not associated with either sTNFR1 or sTNFR2 levels. However, after controlling for GFR, the correlation between AER and sTNFR1 became significant (r = 0.47, P = 0.03). sTNFR1 correlated with age (r = 0.65, P < 0.001), mesangial expansion (r = 0.59, P = 0.004) and interstitial fraction (r = 0.58, P = 0.005). After controlling for age, body mass index and blood pressure, the association of TNFR1 with mesangial expansion persisted significant. Circulating sTNFR2 concentrations were not significantly associated with histological changes. In summary, structural kidney damage in patients with type 2 diabetes is associated with TNF-alpha system activity and specifically with plasma sTNFR1 concentrations. PMID- 22042133 TI - Does ranibizumab (Lucentis(r)) change retrobulbar blood flow in patients with neovascular age-related macular degeneration? AB - PURPOSE: To investigate the effects of intravitreal ranibizumab on retrobulbar blood flow in patients with neovascular age-related macular degeneration (AMD). METHODS: Thirty-one eyes of 30 patients with neovascular AMD were examined prospectively by both color Doppler imaging and fundus fluorescein angiography. Color Doppler imaging was used to measure the maximum and minimum velocities of the central retinal vein, peak systolic/end-diastolic velocities of blood flows, and pulsatility index and resistivity index values in the central retinal artery, nasal/temporal posterior ciliary arteries (NPCA/TPCA) and ophthalmic artery. The t test for paired samples was used for comparing retrobulbar blood flow values before and after intravitreal ranibizumab (Lucentis(r)) injection in the study and control groups. RESULTS: There was a statistically significant (p < 0.05) difference between the pre-injection and post-injection end-diastolic velocities of the NPCA and TPCA and resistivity index values of TPCA. The other parameters showed no statistically significant difference. CONCLUSION: Our results show that intravitreal ranibizumab injection increases retrobulbar blood flow. PMID- 22042136 TI - Decision making for health care managers and supervisors: theory into practice. AB - Health care managers and supervisors make decisions throughout the day. Often, they use the common steps of decision making. This article describes common decision theories that underpin the steps. The article includes specific examples of applications of the theories and a glossary of terms. Experienced and novice health care managers and supervisors can improve their decision making by matching concepts from the decision theories to their problems. PMID- 22042134 TI - Heat shock factor 1 protects against lung mycoplasma pneumoniae infection in mice. AB - Heat shock factor 1 (HSF1) is a transcriptional factor that controls the induction of heat shock proteins (e.g. HSP70) in response to stress. Bacterial infections contribute to the pathobiology of chronic lung diseases such as chronic obstructive pulmonary disease and asthma. Whether HSF1 is critical to lung bacterial infection remains unknown. This study is aimed at investigating the impact of HSF1 deficiency on lung Mycoplasma pneumoniae (Mp) infection and elucidating the underlying molecular mechanisms, such as Toll-like receptor 2 (TLR2) signaling. HSF1(-/-) and HSF1(+/+) mice were intranasally infected with Mp or saline and sacrificed 4, 24 and 72 h after treatment. HSF1(-/-) mice had a higher lung Mp load than HSF1(+/+) mice. Mp-induced lung TLR2, nuclear factor kappaB and associated inflammation [e.g. keratinocyte-derived chemokine (KC), neutrophils and histopathology] were delayed in HSF1(-/-) mice as compared to HSF1(+/+) mice. HSP70 protein levels in bronchoalveolar lavage fluid of HSF1(-/-) mice were decreased. Furthermore, in response to Mp infection, HSF1(-/-) alveolar macrophages had less TLR2 mRNA expression and KC production than HSF1(+/+) counterparts. Nuclear factor-kappaB activity and KC production in HSF1(-/-) macrophages could be rescued by addition of exogenous HSP70 protein. These data suggest that HSF1 is necessary to initiate host defense against bacterial infection partly through promoting early TLR2 signaling activation. PMID- 22042137 TI - Serving distinct populations: performance in Medicaid HMOs and commercial HMOs. AB - The objective of this study was to compare the preventable emergency department (ED) admissions of Medicaid health maintenance organization (HMO) beneficiaries and commercial HMO beneficiaries in the state of Florida, in addition to analyzing the effect of HMO market conditions in relation to these admissions. Paired and unpaired t tests and 10 regression equations were estimated using ED hospital admission data to examine the differences between Medicaid and commercial HMOs in 5 commonly recognized preventable hospitalization conditions. For the same preventable ED admissions, Medicaid and commercial HMO beneficiaries had statistically different rates of admission. In 3 of 5 conditions, Medicaid HMO beneficiaries had more preventable ED admissions than did commercial HMOs for the same conditions. HMO market conditions did not have a statistically significant association with preventable ED admissions for either beneficiary group, whereas teaching status and the percentage of females admitted to the hospital under a given HMO payer type had the greatest effect on preventable ED admissions. Whereas uncontrolled comparisons of preventable ED admissions are statistically different between Medicaid and commercial HMO beneficiaries, controlling for hospital and patient characteristics, market conditions do not affect the rate of preventable ED admissions. PMID- 22042138 TI - The improving efficiency frontier of inpatient rehabilitation hospitals. AB - This study uses a linear programming technique called data envelopment analysis to identify changes in the efficiency frontier of inpatient rehabilitation hospitals after implementation of the prospective payment system. The study provides a time series analysis of the efficiency frontier for inpatient rehabilitation hospitals in 2003 immediately after implementation of PPS and then again in 2006. Results indicate that the efficiency frontier of inpatient rehabilitation hospitals increased from 84% in 2003 to 85% in 2006. Similarly, an analysis of slack or inefficiency shows improvements in output efficiency over the study period. This clearly documents that efficiency in the inpatient rehabilitation hospital industry after implementation of PPS is improving. Hospital executives, health care policymakers, taxpayers, and other stakeholders benefit from studies that improve health care efficiency. PMID- 22042140 TI - Compassion fatigue and burnout: what managers should know. AB - Most health care employees experience and are bolstered by compassion satisfaction as they deal with patients in need. However, the more empathetic a health care provider is, the more likely he or she will experience compassion fatigue. Compassion fatigue is a negative syndrome that occurs when dealing with the traumatic experiences of patients, and examples of symptoms include intrusive thoughts, sleeping problems, and depression. Compassion fatigue is different from burnout. Compassion fatigue is a rapidly occurring disorder for primary health care workers who work with suffering patients, whereas burnout, a larger construct, is a slowly progressing disorder for employees who typically are working in burdensome organizational environments. Managers can mitigate problems associated with compassion fatigue with a number of interventions including patient reassignments, formal mentoring programs, employee training, and a compassionate organizational culture. With burnout, health care managers will want to focus primarily on chronic organizational problems. PMID- 22042141 TI - An empirical investigation of the differences between male and female medical school physicians. AB - The purpose of this research was to investigate gender-related differences among medical school faculty in a variety of areas such as information technology, medical malpractice, compensation, patient care, and carrier satisfaction. The Center for Studying Health System Change's 2008 Health Tracking Physician survey data consisting of 326 medical school faculty belonging to the American Medical Association were used in this study. t Tests indicate that female physicians practicing in medical schools were younger, had less experience, reported lower compensation, and were more likely to be primary care physicians. Male medical school physicians were significantly more concerned about being involved in a malpractice lawsuit. They reported a significantly higher percentage on income based on productivity-related factors. Male physicians also reported getting a significantly higher level of goods and services from drug companies. They also provided more hours of medical service for no or reduced fee in the previous month and higher levels of career satisfaction. Implications of this research are discussed. PMID- 22042142 TI - Electronic fall surveillance system model. AB - Of primary concern to health care facilities today is the reduction of preventable injuries such as patient falls that often lead to serious and fatal injuries and result in increased lengths of stays, resource demands, costs, and lawsuits. Although all patients have the capacity to fall, a major challenge is to identify the presence of key risk factors exhibited by a patient as soon as possible to reduce the likelihood of an adverse fall event. Currently, fall risk assessment and prevention practices focus on nurses identifying the risk factors for falls with a limited use of technology. This article introduces a preliminary falls risk assessment and prevention model that uses standardized clinical and operational performance indicators linked through the Web to the patient's electronic health record to produce an electronic Fall Surveillance System. The use of an integrated Fall Surveillance System linked directly to the electronic health record allows for the implementation of quick "real-time" preventive intervention that would dramatically improve the quality and costs of patient care. PMID- 22042143 TI - A conceptual framework for achieving balance between innovation and resilience in optimizing emergency department operations. AB - This study presents a comprehensive review of theories and practices pertaining to emergency department operations, service innovations, and risk management, focusing on the areas of value creation and operational resilience. It includes a critical examination of how these 2 important areas both contrast with and complement each other. A dynamic systems view was applied to this effect to illuminate the interactions. On the basis of the knowledge gained from this exercise, a system-level conceptual framework was developed to suggest how to rationally optimize emergency department operations. PMID- 22042144 TI - The manager and equipment decisions: the capital budget. AB - As part of his or her role in preparing a departmental budget, a manager must often become involved in budgeting for capital expenditures, those purchases that are of a type and sufficient dollar value to be capitalized and depreciated. Depending on the value of a proposed purchase, the department manager may have only a partial voice in the process; some significant purchases will require administrative approval, whereas some major acquisitions will require approval by the board of directors. Planning for possible capital purchases should begin well before the start of the annual budget exercise. Listing a capital item in the department's budget request does not imply approval; often, there are many more "needs" than there are capital funds available. Therefore, there must be a consistent process for identifying the proposed purchases that will be funded, such process necessarily including detailed specification of the need for a particular capital purchase, identification of all reasonable alternatives, consideration of any constraints, detailed financial comparison of alternatives, assessment of intangible factors, and a recommended choice. PMID- 22042145 TI - Ebf2 marks early cortical neurogenesis and regulates the generation of cajal retzius neurons in the developing cerebral cortex. AB - Mammalian cortical neurogenesis occurs on a precise time schedule during development. The earliest born neurons form the preplate and later separate into layer 1, which includes Cajal-Retzius (C-R) neurons, and the subplate. The preplate and its derivatives play a critical role in regulating subsequent neuron migration and cortical lamination. Using an early B cell factor 2 (Ebf2)-enhanced green fluorescent protein (EGFP) transgenic mouse line, we show that Ebf2-EGFP is expressed in the preplate and persists in C-R neurons, allowing us to follow the development of these early born neurons. Therefore, Ebf2 is a genetic marker for preplate neurons from the earliest stage of their differentiation and C-R cells after the preplate is split. Additionally, we examined the function of Ebf2 in the development of C-R neurons using both lentiviral-mediated knock-down overexpression approaches to perturb Ebf2 expression. Our data show that Ebf2 overexpression increases the generation of early born neurons including C-R cells, while Ebf2 knock-down decreases it, without affecting the generation of other layer-specific neurons in vitro. These results indicate that Ebf2 is important for early cortical neurogenesis and regulates the generation of C-R neurons in the developing cerebral cortex. PMID- 22042146 TI - Asymmetric cyanation of nitroalkenes catalyzed by a salen-titanium catalyst. AB - The salen-Ti complex catalyzed cyanation of nitroolefins was accomplished via the silyl nitronate intermediate for the synthesis of chiral beta-nitronitriles with e.r. up to 92 : 8 and high yields (up to 90%). The catalyst also kept a high turnover frequency at room temperature. The yield and enantioselectivity of the protocol were slightly affected even in a 10 mmol scale. PMID- 22042147 TI - Hematopoietic cell transplantation for primary plasma cell leukemia: results from the Center for International Blood and Marrow Transplant Research. AB - There are limited data on hematopoietic cell transplantation (HCT) in primary plasma cell leukemia (pPCL), an aggressive plasma cell disorder. We report outcomes of 147 patients with pPCL receiving autologous (n=97) or allogeneic (n=50) HCT within 18 months after diagnosis between 1995 and 2006. Median age was 56 years and 48 years for autologous HCT and allogeneic HCT, respectively. Progression-free survival (PFS) at 3 years was 34% (95% confidence interval (CI), 23-46%) in the autologous group and 20% (95% CI, 10-34%) in the allogeneic group. Cumulative incidence of relapse at 3 years was 61% (95% CI, 48-72%) in the autologous group and 38% (95% CI, 25-53%) in the allogeneic group. Overall survival (OS) at 3 years was 64% (95% CI, 52-75%) in the autologous group and 39% (95% CI, 26-54%) in the allogeneic group. Non-relapse mortality (NRM) at 3 years was 5% (95% CI, 1-11%) in the autologous group and 41% (95% CI, 28-56%) in the allogeneic group. The encouraging OS after autologous HCT, establishes the safety and feasibility of this consolidative treatment option after initial induction therapy for pPCL. Allogeneic HCT, although associated with a significantly lower relapse rate, carries a much higher risk of NRM and no OS benefit. PMID- 22042148 TI - Passive markers for tracking surgical instruments in real-time 3-D ultrasound imaging. AB - A family of passive echogenic markers is presented by which the position and orientation of a surgical instrument can be determined in a 3-D ultrasound volume, using simple image processing. Markers are attached near the distal end of the instrument so that they appear in the ultrasound volume along with the instrument tip. They are detected and measured within the ultrasound image, thus requiring no external tracking device. This approach facilitates imaging instruments and tissue simultaneously in ultrasound-guided interventions. Marker based estimates of instrument pose can be used in augmented reality displays or for image-based servoing. Design principles for marker shapes are presented that ensure imaging system and measurement uniqueness constraints are met. An error analysis is included that can be used to guide marker design and which also establishes a lower bound on measurement uncertainty. Finally, examples of marker measurement and tracking algorithms are presented along with experimental validation of the concepts. PMID- 22042149 TI - Spread spectrum magnetic resonance imaging. AB - We propose a novel compressed sensing technique to accelerate the magnetic resonance imaging (MRI) acquisition process. The method, coined spread spectrum MRI or simply s(2)MRI, consists of premodulating the signal of interest by a linear chirp before random k-space under-sampling, and then reconstructing the signal with nonlinear algorithms that promote sparsity. The effectiveness of the procedure is theoretically underpinned by the optimization of the coherence between the sparsity and sensing bases. The proposed technique is thoroughly studied by means of numerical simulations, as well as phantom and in vivo experiments on a 7T scanner. Our results suggest that s(2)MRI performs better than state-of-the-art variable density k-space under-sampling approaches. PMID- 22042150 TI - Neural tube closure in mouse whole embryo culture. AB - Genetic mouse models are an important tool in the study of mammalian neural tube closure (Gray & Ross, 2009; Ross, 2010). However, the study of mouse embryos in utero is limited by our inability to directly pharmacologically manipulate the embryos in isolation from the effects of maternal metabolism on the reagent of interest. Whether using a small molecule, recombinant protein, or siRNA, delivery of these substances to the mother, through the diet or by injection will subject these unstable compounds to a variety of bodily defenses that could prevent them from reaching the embryo. Investigations in cultures of whole embryos can be used to separate maternal from intrinsic fetal effects on development. Here, we present a method for culturing mouse embryos using highly enriched media in a roller incubator apparatus that allows for normal neural tube closure after dissection (Crockett, 1990). Once in culture, embryos can be manipulated using conventional in vitro techniques that would not otherwise be possible if the embryos were still in utero. Embryo siblings can be collected at various time points to study different aspects of neurulation, occurring from E7 7.5 (neural plate formation, just prior to the initiation of neurulation) to E9.5 10 (at the conclusion of cranial fold and caudal neuropore closure, Kaufman, 1992). In this protocol, we demonstrate our method for dissecting embryos at timepoints that are optimal for the study of cranial neurulation. Embryos will be dissected at E8.5 (approx. 10-12 somities), after the initiation of neural tube closure but prior to embryo turning and cranial neural fold closure, and maintained in culture till E10 (26-28 somities), when cranial neurulation should be complete. PMID- 22042151 TI - Analysis of lymph node metastatic pattern according to the depth of in-growth in the muscularis propria in T2 rectal cancer for lateral lymph node dissection. AB - BACKGROUND/AIMS: The biological behavior of rectal cancers that invade the muscularis propria (pT2) has not been well studied. We retrospectively studied the pattern of lymph node metastases in patients with T2 rectal cancer. METHODS: We enrolled 88 patients who had undergone curative resection of T2 colorectal cancer through mesorectal excision and lateral pelvic lymph node dissection; we microscopically estimated the maximum depth of muscularis propria invasion and classified the results into 3 groups representing distinct growth patterns. RESULTS: In cases of pT2 colorectal carcinomas, lateral pelvic lymph node metastases depended on the degree of muscularis propria invasion, and the frequency of metastasis increased with the depth of muscularis propria invasion. Lateral pelvic lymph node metastases were not observed when the depth of muscularis propria invasion was less than half of the thickness of the inner circular layer. CONCLUSIONS: These findings suggest that lateral pelvic lymph node metastasis of pT2 colorectal cancer depends on the depth of vertical invasion, which is analogous to the findings in pT1 and pT3 cancers. This information will be useful in select cases in which resection of the lateral pelvic lymph node is required for the treatment of rectal cancer invading the muscularis propria (pT2). PMID- 22042153 TI - Nonlinear system identification by Gustafson-Kessel fuzzy clustering and supervised local model network learning for the drug absorption spectra process. AB - This paper deals with the problem of fuzzy nonlinear model identification in the framework of a local model network (LMN). A new iterative identification approach is proposed, where supervised and unsupervised learning are combined to optimize the structure of the LMN. For the purpose of fitting the cluster-centers to the process nonlinearity, the Gustafsson-Kessel (GK) fuzzy clustering, i.e., unsupervised learning, is applied. In combination with the LMN learning procedure, a new incremental method to define the number and the initial locations of the cluster centers for the GK clustering algorithm is proposed. Each data cluster corresponds to a local region of the process and is modeled with a local linear model. Since the validity functions are calculated from the fuzzy covariance matrices of the clusters, they are highly adaptable and thus the process can be described with a very sparse amount of local models, i.e., with a parsimonious LMN model. The proposed method for constructing the LMN is finally tested on a drug absorption spectral process and compared to two other methods, namely, Lolimot and Hilomot. The comparison between the experimental results when using each method shows the usefulness of the proposed identification algorithm. PMID- 22042152 TI - Bioinspired neural network for real-time cooperative hunting by multirobots in unknown environments. AB - Multiple robot cooperation is a challenging and critical issue in robotics. To conduct the cooperative hunting by multirobots in unknown and dynamic environments, the robots not only need to take into account basic problems (such as searching, path planning, and collision avoidance), but also need to cooperate in order to pursue and catch the evaders efficiently. In this paper, a novel approach based on a bioinspired neural network is proposed for the real-time cooperative hunting by multirobots, where the locations of evaders and the environment are unknown and changing. The bioinspired neural network is used for cooperative pursuing by the multirobot team. Some other algorithms are used to enable the robots to catch the evaders efficiently, such as the dynamic alliance and formation construction algorithm. In the proposed approach, the pursuing alliances can dynamically change and the robot motion can be adjusted in real time to pursue the evader cooperatively, to guarantee that all the evaders can be caught efficiently. The proposed approach can deal with various situations such as when some robots break down, the environment has different boundary shapes, or the obstacles are linked with different shapes. The simulation results show that the proposed approach is capable of guiding the robots to achieve the hunting of multiple evaders in real-time efficiently. PMID- 22042154 TI - Reduced-size kernel models for nonlinear hybrid system identification. AB - This brief paper focuses on the identification of nonlinear hybrid dynamical systems, i.e., systems switching between multiple nonlinear dynamical behaviors. Thus the aim is to learn an ensemble of submodels from a single set of input output data in a regression setting with no prior knowledge on the grouping of the data points into similar behaviors. To be able to approximate arbitrary nonlinearities, kernel submodels are considered. However, in order to maintain efficiency when applying the method to large data sets, a preprocessing step is required in order to fix the submodel sizes and limit the number of optimization variables. This brief paper proposes four approaches, respectively inspired by the fixed-size least-squares support vector machines, the feature vector selection method, the kernel principal component regression and a modification of the latter, in order to deal with this issue and build sparse kernel submodels. These are compared in numerical experiments, which show that the proposed approach achieves the simultaneous classification of data points and approximation of the nonlinear behaviors in an efficient and accurate manner. PMID- 22042155 TI - Synchronization of continuous dynamical networks with discrete-time communications. AB - In this paper, synchronization of continuous dynamical networks with discrete time communications is studied. Though the dynamical behavior of each node is continuous-time, the communications between every two different nodes are discrete-time, i.e., they are active only at some discrete time instants. Moreover, the communication intervals between every two communication instants can be uncertain and variable. By choosing a piecewise Lyapunov-Krasovskii functional to govern the characteristics of the discrete communication instants and by utilizing a convex combination technique, a synchronization criterion is derived in terms of linear matrix inequalities with an upper bound for the communication intervals obtained. The results extend and improve upon earlier work. Simulation results show the effectiveness of the proposed communication scheme. Some relationships between the allowable upper bound of communication intervals and the coupling strength of the network are illustrated through simulations on a fully connected network, a star-like network, and a nearest neighbor network. PMID- 22042156 TI - Symmetric nonnegative matrix factorization: algorithms and applications to probabilistic clustering. AB - Nonnegative matrix factorization (NMF) is an unsupervised learning method useful in various applications including image processing and semantic analysis of documents. This paper focuses on symmetric NMF (SNMF), which is a special case of NMF decomposition. Three parallel multiplicative update algorithms using level 3 basic linear algebra subprograms directly are developed for this problem. First, by minimizing the Euclidean distance, a multiplicative update algorithm is proposed, and its convergence under mild conditions is proved. Based on it, we further propose another two fast parallel methods: alpha-SNMF and beta -SNMF algorithms. All of them are easy to implement. These algorithms are applied to probabilistic clustering. We demonstrate their effectiveness for facial image clustering, document categorization, and pattern clustering in gene expression. PMID- 22042157 TI - Hydrodynamic flow in a synaptic cleft during exocytosis. AB - It is shown that exocytosis in a chemical synapse may be accompanied by "microjet" formation due to the overpressure that exists in the vesicles. This mechanism may take place either at complete fusion of a vesicle with the presynaptic membrane or in the so-called kiss-and-run mode of neurotransmitter release. A simple hydrodynamic model of the viscous incompressible flow arising in the synaptic cleft is suggested. The occurrence of hydrodynamic flow (microjet) leads to more efficient transport of neurotransmitter than in the case of classical diffusive transport. PMID- 22042158 TI - The pH-dependent induction of lipid membrane ionic permeability by N-terminally lysine-substituted analogs of gramicidin A. AB - Insertion of charged groups at the N-terminus of the gramicidin A (gA) amino acid sequence is considered to be fatal for peptide channel-forming activity because of hindrance to the head-to-head dimer formation. Here the induction of ionic conductivity in planar bilayer lipid membranes (BLM) was studied with gA analogs having lysine either in the first ([Lys1]gA) or the third ([Lys3]gA) position. If added to the bathing solution at neutral or acidic pH, these analogs, being protonated and thus positively charged, were unable to induce ionic current across BLM. By contrast, at pH 11 the induction of BLM conductivity was observed with both lysine-substituted analogs. Based on the dependence of the macroscopic current on the side of the peptide addition, sensitivity to calcium ions and susceptibility to sensitized photoinactivation, as well as on the single-channel properties of the analogs, we surmise that at alkaline pH [Lys1]gA formed channels with predominantly single-stranded structure of head-to-head helical dimers, whereas [Lys3]gA open channels had the double-stranded helical structure. CD spectra of the lysine-substituted analogs in liposomes were shown to be pH dependent. PMID- 22042159 TI - The mere anticipation of an interaction with a woman can impair men's cognitive performance. AB - Recent research suggests that heterosexual men's (but not heterosexual women's) cognitive performance is impaired after an interaction with someone of the opposite sex (Karremans et al., 2009). These findings have been interpreted in terms of the cognitive costs of trying to make a good impression during the interaction. In everyday life, people frequently engage in pseudo-interactions with women (e.g., through the phone or the internet) or anticipate interacting with a woman later on. The goal of the present research was to investigate if men's cognitive performance decreased in these types of situations, in which men have little to no opportunity to impress her and, moreover, have little to no information about the mate value of their interaction partner. Two studies demonstrated that men's (but not women's) cognitive performance declined if they were led to believe that they interacted with a woman via a computer (Study 1) or even if they merely anticipated an interaction with a woman (Study 2). Together, these results suggest that an actual interaction is not a necessary prerequisite for the cognitive impairment effect to occur. Moreover, these effects occur even if men do not get information about the woman's attractiveness. This latter finding is discussed in terms of error management theory. PMID- 22042160 TI - The second to fourth digit ratio and age at first marriage in semi-nomadic people from Namibia. AB - The second to fourth digit ratio (2D:4D) is used as a potential marker for prenatal androgen exposure. It is associated with many behavioral and biological variables, including fertility and sexual behavior. However, direct association between 2D:4D and reproductive success--in populations where no contraceptives are used--has not been investigated. Here, we present a study conducted among the semi-nomad Himba population living in northern Namibia. 2D:4D ratios were calculated for a sample of this population (N=99; 60 women, 39 men), and the results were correlated with age, marital status, age at first marriage, number of children, and number of marriages. As found in the majority of previous studies, males had lower 2D:4D ratios than females. The 2D:4D ratio did not correlate with number of children. Females and males with a more masculine 2D:4D were married earlier and were more likely to have a husband or wife. We suggest that mating preferences for females with masculine 2D:4D are related to masculinity of phenotypic and personality traits of such women, which are beneficial in harsh environmental conditions and/or higher facial masculinity, which influences the perceived age of an individual. At the same time, masculine (physically strong, dominant, and hardworking) males might gather resources necessary to marry their first wife earlier. PMID- 22042161 TI - Risk, individual differences, and environment: an Agent-Based Modeling approach to sexual risk-taking. AB - Risky sexual behaviors, including the decision to have unprotected sex, result from interactions between individuals and their environment. The current study explored the use of Agent-Based Modeling (ABM)-a methodological approach in which computer-generated artificial societies simulate human sexual networks-to assess the influence of heterogeneity of sexual motivation on the risk of contracting HIV. The models successfully simulated some characteristics of human sexual systems, such as the relationship between individual differences in sexual motivation (sexual excitation and inhibition) and sexual risk, but failed to reproduce the scale-free distribution of number of partners observed in the real world. ABM has the potential to inform intervention strategies that target the interaction between an individual and his or her social environment. PMID- 22042163 TI - On the mathematical properties of the structural similarity index. AB - Since its introduction in 2004, the structural similarity (SSIM) index has gained widespread popularity as a tool to assess the quality of images and to evaluate the performance of image processing algorithms and systems. There has been also a growing interest of using SSIM as an objective function in optimization problems in a variety of image processing applications. One major issue that could strongly impede the progress of such efforts is the lack of understanding of the mathematical properties of the SSIM measure. For example, some highly desirable properties such as convexity and triangular inequality that are possessed by the mean squared error may not hold. In this paper, we first construct a series of normalized and generalized (vector-valued) metrics based on the important ingredients of SSIM. We then show that such modified measures are valid distance metrics and have many useful properties, among which the most significant ones include quasi-convexity, a region of convexity around the minimizer, and distance preservation under orthogonal or unitary transformations. The groundwork laid here extends the potentials of SSIM in both theoretical development and practical applications. PMID- 22042164 TI - Drug-induced pseudoleucoderma: a commentary. PMID- 22042165 TI - Laparoscopic type 7 total hysterectomy and adnexectomy with or without Burch colposuspension: operative technique with the LigaSure device and results. AB - INTRODUCTION: The purpose of the present study was to investigate the use of an operative technique incorporating the LigaSure vessel sealing system in patients undergoing type 7 total laparoscopic hysterectomy (TLH) and adnexectomy with or without Burch colposuspension. METHODS: Data were collected for 68 patients who underwent type 7 TLH with adnexectomy. Analyzed variables included patient characteristics (age, body mass index (BMI), parity, medical and surgical history, indications for hysterectomy, weight of the removed uterus), operative data (operative time, procedures performed in addition to TLH, intraoperative blood loss), complications, difference between preoperative and postoperative hemoglobin levels, and length of hospital stay. RESULTS: Mean age was 53.7 +/- 6.9 years (range 46-74) and mean body mass index was 27.9 +/- 6.1 kg/m(2) (range 19.4-45.7). Overall mean operative time was 100.4 +/- 31.7 min (range 60-180), mean intraoperative blood loss was 98.1 +/- 96.9 ml (range 0-700), and the mean difference between preoperative and postoperative hemoglobin levels was 1.39 +/- 0.6 g/dl (range 0-3.4). Mean weight of the removed uteruses was 229.4 +/- 174.8 g (range 60-750). Mean hospital stay was 1.12 +/- 0.7 days (range 1-7). Additional operative procedures included Burch colposuspension (15; 22.1%), adhesiolysis (9; 13.2%), cholecystectomy (2; 2.9%), transabdominal preperitoneal hernia repair (1; 1.5%) and repair of intraoperative bladder injury (1; 1.5%). Major intraoperative complications were encountered in two patients. In one, the left ureter was injured and in the other the bladder was injured. Conversion to open surgery was not needed in any of the patients. CONCLUSION: The procedure we describe here for type 7 TLH with adnexectomy, performed alone or with additional Burch colposuspension, appears to be safe and effective. PMID- 22042167 TI - Subsequent pregnancy after two uterine artery embolizations. PMID- 22042166 TI - Lower urinary tract symptoms in primiparous women before and during pregnancy. AB - OBJECTIVE: Lower urinary tract symptoms (LUTS), in particular urinary incontinence (UI), commonly develops during pregnancy or following delivery. This study was conducted to investigate the prevalence of the LUTS before and during pregnancy, and to demonstrate the relationships between various obstetric parameters and UI. METHODS: For this observational study, 1,501 consecutive primiparae who delivered at >= 36 gestational weeks were recruited in a tertiary hospital. A urogynecological questionnaire was used to assess the prevalence of LUTS before and during pregnancy. The relationships between various obstetric parameters and UI were analyzed. RESULTS: Prevalence of LUTS increased over the course of pregnancy. The most commonly reported LUTS symptoms, regardless of pregnancy trimester, were nocturia (51.1%) and frequency (40.3%), UI (37.5%), urgency (31.1%), incomplete bladder emptying (26.3%), straining (15.3%), and voiding difficulty (14.5%). Stress UI (SUI) (26.7%) was more common during pregnancy than mixed UI (6.1%) or urge UI (4.7%). Women with a prepregnancy BMI >30 were at increased risk of developing de novo SUI during pregnancy. Urge incontinence during pregnancy was associated with smoking. CONCLUSIONS: The prevalence of LUTS generally increased with gestational age. UI during pregnancy was associated with prepregnancy BMI and smoking. PMID- 22042168 TI - Ta2O5 nanowires: a novel synthetic method and their solar energy utilization. AB - Single-crystalline uniform Ta(2)O(5) nanowires are prepared by a novel synthetic route. The formation of the nanowires involves an oriented attachment process caused by the reduction of surface energy. The nanowires are successfully applied to photocatalytic H(2) evolution, contaminant degradation, and dye-sensitized solar cells (DSCs). The Ta(2)O(5)-based DSCs reveal a significant photovoltaic response, which has not been reported. As a photocatalyst, the Ta(2)O(5) nanowires possess high H(2) evolution efficiency under Xe lamp irradiation, nearly 27-fold higher than the commercial powders. A better performance of photocatalytic contaminant degradation is also observed. Such improvements are ascribed to better charge transport ability for the single-crystalline wire and a higher potential energy of the conduction band. This new synthetic approach using a water-soluble precursor provides a versatile way to prepare nanostructured metal oxides. PMID- 22042169 TI - LDA merging and splitting with applications to multiagent cooperative learning and system alteration. AB - To adapt linear discriminant analysis (LDA) to real-world applications, there is a pressing need to equip it with an incremental learning ability to integrate knowledge presented by one-pass data streams, a functionality to join multiple LDA models to make the knowledge sharing between independent learning agents more efficient, and a forgetting functionality to avoid reconstruction of the overall discriminant eigenspace caused by some irregular changes. To this end, we introduce two adaptive LDA learning methods: LDA merging and LDA splitting. These provide the benefits of ability of online learning with one-pass data streams, retained class separability identical to the batch learning method, high efficiency for knowledge sharing due to condensed knowledge representation by the eigenspace model, and more preferable time and storage costs than traditional approaches under common application conditions. These properties are validated by experiments on a benchmark face image data set. By a case study on the application of the proposed method to multiagent cooperative learning and system alternation of a face recognition system, we further clarified the adaptability of the proposed methods to complex dynamic learning tasks. PMID- 22042170 TI - DP2 (CRTh2) antagonism reduces ocular inflammation induced by allergen challenge and respiratory syncytial virus. AB - BACKGROUND: Allergic conjunctivitis is characterized by itchy, watery and swollen eyes which occur in response to exposure to seasonal or environmental allergens. The early phase reaction of allergic conjunctivitis is primarily mediated by mast cell degranulation while the late phase reaction is driven by Th2 cells and eosinophils. Prostaglandin D(2) (PGD(2)), released from mast cells, is present in allergic conjunctival tears and may elicit classical allergic responses via interaction with the high-affinity DP2 receptor (chemoattractant receptor homologous molecule expressed on Th2 cells, CRTh2). Furthermore, antagonism of this receptor is well known to inhibit eosinophil chemotaxis, basophil activation and Th2 cytokine production. PGD(2), therefore, may be involved in both early and late phase reactions in response to allergen challenge. METHODS: Thus, we explored whether our novel and selective DP2 antagonist AM156 would be efficacious in animal models of allergic conjunctivitis. Furthermore, as respiratory syncytial virus (RSV) has been implicated in the pathogenesis of allergic conjunctivitis, we examined the effects of DP2 antagonism in a murine model of RSV ocular infection. RESULTS: Utilizing a guinea pig ovalbumin model and a murine ragweed model we demonstrated that AM156 reduces redness, discharge and swelling in response to allergen challenge. These effects were equal to or greater than those of current clinical treatment options for allergic conjunctivitis including topical corticosteroids and a dual-mechanism antihistamine and decongestant. AM156 significantly reduced RSV-induced ocular inflammation and IL-4 production. CONCLUSION: These results suggest that a topical DP2 antagonist such as AM156 may represent a novel therapeutic for allergic conjunctivitis. PMID- 22042171 TI - Dementia associated with Parkinson's disease: usefulness of the Movement Disorder Society diagnostic criteria in Brazil. PMID- 22042172 TI - Dementia in Parkinson's disease: a Brazilian sample. AB - To determine the prevalence of dementia associated with Parkinson's disease (PD D) in a Brazilian sample adopting clinical and diagnostic procedures recommended by the Movement Disorders Society (MDS). Sixty-seven patients were consecutively submitted to neurological, neuropsychological and functional examinations. PD-D was established according to MDS clinical criteria (Level II) and clinical procedures for PD-D (Level I) and prevalence rate was compared between the levels adopted. Ten patients (14.9%) were diagnosed as demented by Level I criteria whereas sixteen (23.8%) were diagnosed based on Level II criteria. Level I criteria had low sensitivity in detecting PD-D (31.25%), but greater specificity (90.19). The PD-D group had significantly worse performance on all neuropsychological tests, were older (p<0.001), had an older age of onset of disease (p<0.01), had lower educational level (p<0.02) and had higher scores on functional scales. Current age (p=0.046) and Hoehn & Yahr score (p=0.048) were predictors for developing PD-D. PMID- 22042173 TI - Health self-perception by dementia family caregivers: sociodemographic and clinical factors. AB - Caring for a demented family member has been associated with burden. Studies concerning health self-perception of family caregivers are still scarce. OBJECTIVE: To investigate caregivers perceived health and to look into relationships with patients and caregivers' sociodemographic and clinical data. METHOD: Dyads of dementia outpatients and family caregivers (n=137) were assessed with Mini Mental State Examination, Functional Activities Questionnaire, Neuropsychiatric Inventory and Clinical Dementia Rating. Caregivers answered Sociodemographic Questionnaire, Beck Depression and Anxiety Inventories, Zarit Burden Interview and Maslach Burnout Inventory. RESULTS: Caregivers poor perceived health was associated with emotional exhaustion, burden, depression and anxiety. Logistic regression analyses revealed caregivers' age, anxiety and physical problem as the main predictors of health self-perception. CONCLUSION: Aged family caregivers with anxiety who also report physical problem characterize a group at risk for poor self-perceived health. Evaluation of health self perception may be useful for designing interventions to improve anxiety and physical health. PMID- 22042174 TI - Botulinum toxin type A and cervical dystonia: a seven-year follow-up. AB - Most cases of cervical dystonia (CD) are idiopathic, and focal injections of botulinum toxin A (BoNT/A) are the treatment of choice. The objective of our study was to document the effects of long-term BoNT/A treatment in idiopathic CD patients. Fifty-eight patients with idiopathic CD were recruited from March 2001 to May 2002. Twenty-eight of the subjects were available for reassessment after seven years. During this period, all had received regular treatment with BoNT/A injections. Clinical information about patients and the severity of CD (TWSTRS and VAPS) at baseline assessment (2001-2002) and follow-up (2008-2009) was compared. Significant motor improvement was detected based on TWSTRS scale scores, which were used to analyze clinical severity (19.6 +/- 6.6 and 17.7 +/- 4.8; p<0.05). There was no improvement in the severity of cervical pain (p=0.43). In conclusion, BoNT/A was a safe and effective long-term therapy for CD. PMID- 22042175 TI - Neuroleptic malignant syndrome. AB - Neuroleptic malignant syndrome (NMS) is a potentially fatal adverse event associated with the use of antipsychotics (AP). The objective of this study was to investigate the profile of cases of NMS and to compare our findings with those published in similar settings. A series of 18 consecutive patients with an established diagnosis of NMS was analyzed, gathering data on demography, symptoms and signs. Two thirds of all cases involved woman with a past medical history of psychiatric disorder receiving relatively high doses of AP. The signs and symptoms of NMS episodes were similar to those reported in other series and only one case had a fatal outcome, the remaining presenting complete recovery. As expected, more than two thirds of our cases were using classic AP (68%), however the clinical profile of these in comparison with those taking newer agent was similar. Newer AP also carry the potential for NMS. PMID- 22042176 TI - Lees' syndrome: a case series. AB - We report a case series of dopamine dysregulation syndrome, previously known as hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies, now designated as Lees' syndrome. PMID- 22042177 TI - Electronystagmography findings in spinocerebellar ataxia type 3 (SCA3) and type 2 (SCA2). AB - OBJECTIVE: To describe the alterations observed in electronystagmography (ENG) of patients with spinocerebellar ataxia (SCA) types 2 and 3. METHOD: Sixteen patients were studied and the following procedures were carried out: anamnesis, otorhinolaryngological and vestibular evaluations. RESULTS: The clinical findings in the entire group of patients were: gait disturbances (93.75%), dysarthria (43.75%), headache (43.75%), dizziness (37.50%) and dysphagia (37.50%). In the vestibular exam, the rotatory (62.50%) and caloric (75%) tests were among those which presented the largest indexes of abnormalities; the presence of alterations in the exams was 87.50%, with a predominance of central vestibular disorders in 68.75% of the exams. CONCLUSION: Vestibular exams could be an auxiliary tool to investigate SCAs, besides a precise clinical approach and, particularly, molecular genetic tests. PMID- 22042178 TI - Mortality in children with severe epilepsy: 10 years of follow-up. AB - Epilepsy is the main neurological condition in children and adolescents. Unfortunately patients with medical refractory epilepsy are more susceptible for clinical complications and death. We report a prospectively evaluated cohort of children followed for approximately 10 years. Fifty-three of 1012 patients died. Forty-two patients died due to epilepsy or its clinical complications and the main causes of death were pneumonia (in 16 cases), sepsis (in 9 patients), status epilepticus (in 8 patients). In 11 patients cause of death was sudden unexpected death in epilepsy (SUDEP). Mental retardation was significantly more frequent in patients who did not die from SUDEP. SUDEP may be a significant condition associated with mortality in children and adolescents with epilepsy. PMID- 22042179 TI - Self-esteem, social support perception and seizure controllability perception in adolescents with epilepsy. AB - OBJECTIVE: Compare the self-esteem of adolescents with epilepsy and adolescents without epilepsy and relate it to social support and seizure controllability perception. METHOD: The study sample consisted: case participants (34 subjects) attending the pediatric epilepsy clinic of University Hospital and control participants (30 subjects) from public schools in Campinas-SP. The instruments utilized were: identification card with demographic and epilepsy data, a semi structured interview on aspects of the disease, and a Self-Esteem Multidimensional Scale. RESULTS: There was no significant difference between the two groups but majority of adolescents with epilepsy presented higher self esteem rate, have knowledge about epilepsy, presented high levels of social support and seizure controllability perception. There was no significant relationship between social support and seizure controllability perception with self-esteem. CONCLUSION: Knowledge about epilepsy, social support such good controllability seizure perception seem are important contingencies for a better evaluation of self esteem in adolescents with epilepsy. PMID- 22042180 TI - Depression in patients with refractory temporal lobe epilepsy. AB - OBJECTIVE: To evaluate the comorbidity of depressive disorders in patients with refractory temporal lobe epilepsy (TLE). METHOD: We evaluated 25 consecutive patients with refractory TLE (16 women and 9 men), using semi-structured psychiatric interviews, according to the International Classification of Diseases (ICD-10), and the Beck Depression Inventory. RESULTS: Seventeen of 25 patients (68%) had depressive disorder: 6 with dysthymia, three with major depressive episodes and 8 with recurrent depressive disorders. Two (8%) were diagnosed with mixed anxiety and depression. Only 5 of 17 patients (29.4%) were previously diagnosed with depressive disorder and received prior antidepressant treatment. Duration of epilepsy was significantly higher in patients with depressive disorder (p=0.016), but there was no relationship between depression and seizure frequency. CONCLUSION: This study confirmed that depressive disorders are common and underdiagnosed in patients with TLE refractory to AEDs. Patients with longer duration of epilepsy are at higher risk of having depression. PMID- 22042181 TI - Low educational level effects on the performance of healthy adults on a Neuropsychological Protocol suggested by the Commission on Neuropsychology of the Liga Brasileira de Epilepsia. AB - OBJECTIVE: To assess cognitive measures and impact of education on cognitive performance (CP) of low educational levels healthy adults (LELHA) on a Neuropsychological Protocol (NP) suggested by the Liga Brasileira de Epilepsia. METHOD: 138 subjects from an Education Program for Adults divided into two, age and gender matched groups of 69 subjects, answered the NP: Group 1 (mean of 6.9 +/- 2.95 months of formal education) and Group 2, 47.8 +/- 10 months. Data were compared as z-scores. RESULTS: The mean IQ was 77.1 +/- 5.50 and 79.4 +/- 3.30 in Groups 1 and 2, respectively (p=0.001). Both performed below the normal curve and Group 1 worse than 2. CP correlated with schooling, especially executive functions (54.1% vs 36.2%) and language (52.9% vs 25.7%). CONCLUSION: LELHA showed significant cognitive impairment in verbal and visuospatial areas. If these results had been obtained in epilepsy patients they would be interpreted as global cognitive impairment. PMID- 22042182 TI - Swallowing disorders after ischemic stroke. AB - OBJECTIVE: To investigate occurrences of swallowing disorders after ischemic stroke. METHOD: This was a retrospective study on 596 medical files. The inclusion criterion was that the patients needed to have been hospitalized with a diagnosis of ischemic stroke; the exclusion criteria were the presence of associated cardiac problems and hospital stay already more than 14 days. RESULTS: 50.5% were men and 49.5% women; mean age 65.3 years (SD= +/- 11.7) (p <= 0.001). Among the risk factors, 79.4% had hypertension, 36.7% had diabetes (p <= 0.001) and 42.7% were smokers. 13.3% of the patients died. Swallowing disorders occurred in 19.6%, among whom 91.5% had mild difficulty and 8.5% had severe difficulty. 87.1% had spontaneous recovery after a mean of 2.4 months. A lesion in the brainstem region occurred in 6.8% (p <= 0.001). CONCLUSION: Swallowing disorders occurred in almost 20% of the population and most of the difficulty in swallowing found was mild. The predictors for swallowing disorders were older age, diabetes mellitus and lesions in the brainstem region. PMID- 22042183 TI - A topographic study on the evaluation of speech and language in the acute phase of a first stroke. AB - Evaluation of speech and language may help in localization of site and extension of brain lesions, particularly in the absence of other neurological signs or radiologically defined injuries. OBJECTIVE: To verify what language tasks are best correlated to which brain regions, in order to develop a test for neurologists in emergency settings. METHOD: Thirty-seven adult first-stroke patients were submitted to cognitive and language tests, and then paired with thirty-seven healthy controls. Patients underwent CT and/or MRI for topographic correlation with test results (p<0.05). RESULTS: All tests were able to distinguish patients from controls, but only word/sentence repetition, naming, ideomotor praxis and, non-significantly, comprehension and counting 1-20 predicted left hemisphere lesions. Repetition was related to perisylvian structures, comprehension to the posterior portion of the middle cerebral artery territory, and fluency to frontal lesions, while naming was accurate only for lesion side. CONCLUSION: Language and cognitive tasks can help in the localization of acute stroke lesions. PMID- 22042184 TI - Therapeutic effects of a horse riding simulator in children with cerebral palsy. AB - OBJECTIVE: To evaluate the efficacy of horse ridding simulator on the sitting postural control of children with spastic diplegia. METHOD: Forty children were randomly divided in a group using the simulator (RS) and a group performing conventional physical therapy (CT). FScan/Fmat equipment was used to register maximal displacement in antero-posterior (AP) and medio-lateral (ML) directions with children in sitting position. At the pre and post intervention stage both groups were classified according to the Gross Motor Function Classification System (GMFCS) and, after intervention, by the AUQEI questionnaire (Autoquestionnaire Qualite de vie Enfant Image). RESULTS: Comparison between groups disclosed statistically significant pos-intervention improvement both in the AP (p<0.0001) as in the ML (p<0.0069) direction in the RS group. CONCLUSION: The horse ridding simulator produced significant improvement in the postural control of children in sitting position, additionally showing a higher motor functionality and a better acceptance of the therapeutic intervention. PMID- 22042185 TI - Oropharyngeal examination as a predictor of obstructive sleep apnea: pilot study of gag reflex and palatal reflex. AB - Obstructive sleep apnea (OSA) has high prevalence and may cause serious comorbidities. The aim of this trial was to show if simple noninvasive methods such as gag reflex and palatal reflex are prospective multivariate assessments of predictor variables for OSA. METHOD: We evaluate gag reflex and palatal reflex, of fifty-five adult patients, and their subsequent overnight polysomnography. RESULTS: Forty-one participants presented obstructive sleep apnea. The most relevant findings in our study were: [1] absence of gag reflex on patients with severe obstructive apnea (p=0.001); [2] absence of palatal reflex on moderate obstructive apnea patients (p=0.02). CONCLUSION: Gag reflex and palatal reflex, a simple noninvasive test regularly performed in a systematic neurological examination can disclose the impact of the local neurogenic injury associated to snoring and/or obstructive sleep apnea syndrome. PMID- 22042186 TI - Sight-dependent quality of life and ophthalmic findings in a group of Brazilian patients with multiple sclerosis. AB - OBJECTIVE: To assess the visual quality of life in patients with multiple sclerosis (MS), and to observe whether this parameter could be correlated to the findings of the ophthalmologic examination. METHOD: The translated and validated 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25) was used to assess the visual quality of life. Clinical data on MS, visual acuity, visual fields, optic coherence tomography (OCT) and disc cupping were used for assessing correlation with VFQ-25. RESULTS: The mean VFQ-25 value was 78.6 +/- 18.2% in 27 patients. VFQ-25 did not correlate with patients' ages, with disability (EDSS), disease duration or medication use. Visual acuity showed a relatively poor (<60%) correlation to VFQ-25, while no correlation could be established between visual fields, OCT and disc cupping with VFQ-25. CONCLUSION: MS patients present several alterations in their eyes and sight that cannot be assessed by isolated measures. Ophthalmological examination of these patients must include many parameters not usually used in standard ophthalmologic consultations. PMID- 22042187 TI - Verbal fluency tests reliability in a Brazilian multicentric study, ELSA-Brasil. AB - Verbal Fluency Tests (VFT) are commonly used to assess executive functions and language in clinical and epidemiological studies. These tests were included to access cognitive function and predictors to its decline in ELSA-Brasil (Longitudinal Study of Adults' Health), a cohort that investigates incidence and predictors of chronic diseases among 15,000 civil servants from six public educational institutions. OBJECTIVE: To investigate the reliability of VFT scoring by supervisors of. ELSA research centers, who independently judged 120 category (animals) and 120 phonemic (F letter) tests. METHOD: Their scores were compared to a reference standard score obtained by independent judgment of two experts. Intraclass correlation coefficient ratings reliability and Bland-Altman plot examined patterns of ratings disagreement. RESULTS: Scores were very similar among ELSA centers and a high level of agreement was observed between each center and the reference standard. CONCLUSION: The high consistency of VFT scores confirms reliability and validity of the test and assures quality for its use in multicenter studies. PMID- 22042188 TI - Posterior fossa decompression with tonsillectomy in 104 cases of basilar impression, Chiari malformation and/or syringomyelia. AB - The prime objective in the surgical treatment of basilar impression (BI), Chiari malformation (CM) and/or syringomyelia (SM) is based on the restoration of the normal cerebrospinal fluid (CSF) dynamics at the craniovertebral junction through the creation of a large artificial cisterna magna. A small suboccipital craniectomy has been emphasized to avoid caudal migration of the hindbrain structures into the vertebral canal. Nevertheless, the results showed downward migration of the hindbrain related to that type of craniectomy. The authors present, otherwise, the results of 104 cases of BI, CM and/or SM, whose surgical treatment was characterized by a large craniectomy with the patient in the sitting position, tonsillectomy, large opening of the fourth ventricle and duraplasty with creation of a large artificial cisterna magna. A significant upward migration of the posterior fossa structures was detected by postoperative magnetic resonance imaging. PMID- 22042189 TI - Atypical presentations of neuromyelitis optica. AB - Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system classically characterized by acute, severe episodes of optic neuritis and longitudinally extensive transverse myelitis, usually with a relapsing course. The identification of an autoantibody exclusively detected in NMO patients against aquaporin-4 (AQP-4) has allowed identification of cases beyond the classical phenotype. Brain lesions, once thought as infrequent, can be observed in NMO patients, but lesions have different characteristics from the ones seen in multiple sclerosis. Additionally, some AQP-4 antibody positive patients may present with a variety of symptoms not being restricted to optic neuritis and acute myelitis during the first attack or in a relapse. Examples are not limited to, but may include patients only with brain and/or brainstem lesions, narcolepsy with hypothalamic lesions or patients with intractable hiccups, nausea and vomiting. The prompt identification of NMO patients with atypical presentations may benefit these patients with institution of early treatment to reduce disability and prevent further attacks. PMID- 22042190 TI - Non-epileptiform EEG abnormalities: an overview. AB - More than 80 years after its introduction by Hans Berger, the electroencephalogram (EEG) remains as an important supplementary examination in the investigation of neurological disorders and gives valuable and accurate information about cerebral function. Abnormal EEG findings may include ictal patterns, interictal epileptiform activity and non-epileptiform abnormalities. The aim of this study is to make an overview on the main non-epileptiform EEG abnormalities, emphasizing the pathologic findings and the importance of their recognition, excluding periodic patterns and EEG physiologic changes. Scientific articles were selected from MEDLINE and PubMed database. The presence of non epileptiform EEG abnormalities provide evidence of brain dysfunction that are not specific to a particular etiology and may be related to a number of disorders affecting the brain. Although these abnormalities are not specific, they can direct attention to the diagnostic possibilities and guide the best treatment choice. PMID- 22042191 TI - The pyramidal syndrome and the pyramidal tract: a brief historical note. AB - The discovery of the pyramidal syndrome and tract is briefly reviewed with emphasis on a few key historical aspects. The pursuit of the relationship between the lateralized deficits resulting from contralateral head trauma begins in the fourth century BC with the Hippocratic School and continues until the present day. PMID- 22042192 TI - Women neurologist: a worldwide and Brazilian struggle. AB - The main aim of this paper was to present some pioneer women neurologist, their struggle to pursue their career and the barriers mainly encountered at the beginning of their professional lives. It was also presented the progressive increasing of the feminine participation in medicine and in the neurology with study based on data of the School of Medicine of the Federal University of Rio de Janeiro and Brazilian Academy of Neurology. Their composition were analyzed according to gender, class and academic rank. In spite of this feminization, there is lack of a women's parallel advancement into leadership positions despite no visible barriers ("glass ceiling"). PMID- 22042193 TI - Spinocerebellar ataxia type 10: disproportionate cerebellar symptoms among at risk subjects induced by small amounts of alcohol. PMID- 22042194 TI - Temporal primary cerebral Ewing sarcoma extended to skull. PMID- 22042195 TI - Isolated hypoglossal nerve palsy: an unusual rare presentation in systemic lupus erythematosus. PMID- 22042196 TI - Pituitary metastasis from adenocarcinoma. PMID- 22042197 TI - Seizure-like activity during etomidate-modified Wada test interfere with the evaluation of cognitive functions? PMID- 22042198 TI - Intramedullary granuloma suggestive of tuberculoma. PMID- 22042199 TI - Anchored fat-fascia graft for clival skull base reconstruction. PMID- 22042200 TI - Cerebellar cryptococcoma in a non-HIV patient. PMID- 22042201 TI - Epidemiological profile in multiple sclerosis patients, Uberaba, MG, Brazil. PMID- 22042202 TI - Pregnancy, epilepsy and quality of life. PMID- 22042207 TI - A novel fluorescent probe for NAD-consuming enzymes. AB - A novel, fluorescent NAD derivative is processed as substrate by three different NAD-consuming enzymes. The new probe has been used to monitor enzymatic activity in a continuous format by changes in fluorescence and, in one case, to directly visualize alternative reaction pathways. PMID- 22042209 TI - Anisotropic elasticity in confocal studies of colloidal crystals. AB - We consider the theory of fluctuations of a colloidal solid observed in a confocal slice. For a cubic crystal we study the evolution of the projected elastic properties as a function of the anisotropy of the crystal using numerical methods based on the fast Fourier transform. In certain situations of high symmetry we find exact analytic results for the projected fluctuations. PMID- 22042210 TI - Genomic analysis of bacteriophage ESP2949-1, which is virulent for Cronobacter sakazakii. AB - Virulent phage ESP2949-1, which was isolated from sewage, has an icosahedral head, a contractile tail, and a double-stranded DNA genome with a length of 49,116 bp with 50.09% G+C content. Phage ESP2949-1 showed 3% similarity to enterobacteria phage TLS. Bioinformatics analysis of the phage genome revealed 43 putative open reading frames (ORFs). Predicted protein products of the ORFs were determined and described. Based on its morphology, phage ESP2949-1 can be classified as a member of the family Myoviridae. To our knowledge, this is the first report of the genomic sequence and characterization of phage ESP2949-1 isolated from sewage. PMID- 22042211 TI - Quantification of HIV-based lentiviral vectors: influence of several cell type parameters on vector infectivity. AB - A human immunodeficiency virus type (HIV-1)-based lentiviral vector pseudotyped with the vesicular stomatitis virus envelope glycoprotein and encoding the GFP reporter gene was used to evaluate different methods of lentiviral vector titration. GFP expression, viral DNA quantification and the efficiency of vector DNA integration were assayed after infection of conventional HIV-1-permissive cell lines and human primary adult fibroblasts with the vector. We found that vector titers based on GFP expression determined by flow cytometry may vary by more than 50-fold depending on the cell type and the promoter-cell combination used. Interestingly, we observed that the viral integration process in primary HDFa cells was significantly more efficient compared to that in SupT1 or 293T cells. We propose that determination of the amount of integrated viral DNA by quantitative PCR be used in combination with the reporter gene expression assay. PMID- 22042212 TI - Preoperative tumor studies using MRI or CT in patients with clinically suspected insulinoma. AB - PURPOSE: Insulinomas are rare tumors that originate from the islet cells of the pancreas. The aims of this study were to localize insulinomas preoperatively using CT and/or MRI in correlation with postoperative pathological results. PATIENTS AND METHODS: Between December 2001 and June 2010, 27 consecutive patients with clinically suspected insulinoma were surgically treated in our university hospital. Preoperative CT (14 of 27 patients) and MRI studies (14 of 27 patients, one patient had both MRI and CT), operation reports, intraoperative ultrasonography reports, and pathological diagnoses were analyzed retrospectively. For each lesion, images were analyzed based on the presence of enhancement or the characteristics of signal intensities. Pathologic correlation was available for all the lesions. RESULTS: The female: male ratio was 2.9, with a mean age of 47.5 years (range 12-82) . Preoperative tumor localization was achieved by means of MRI and CT. A focal pancreatic lesion, which was hypointense on T(1)-weighted sequences, was detected on all the MR images (14 of 27 patients; 100%). These lesions were isointense (4 cases) to slightly hyperintense (10 of 14 cases) on T(2)-weighted sequences. In T(1)-weighted fat-suppressed contrast enhanced sequences, there were two types of enhancement: homogeneously hyperintense lesions (in 10 of 14 cases) or peripherally hyper-, centrally isointense (in 4 of 14 cases). On all the CT images (14 of 27 patients), there was no detectable lesion on precontrast series; on arterial series in 13 of 14 patients (arterial series has not been done in one patient), lesions enhanced hypervascular in contrast to the rest of the pancreas with a mean enhancement of 147 HU (range 113-248) and 95 HU (range 65-141), respectively. On venous series in 13 of 14 patients (venous series has not been done in one patient), there was an enhanced lesion in contrast to the rest of the pancreas with a mean enhancement of 110 HU (range 91-151) and 86 HU (range 65-137), respectively. Intraoperative ultrasonography was performed in 11 of 27 patients to localize the tumor, which correlated with the results of the mentioned preoperative studies. Tumor size ranged from 9 * 11 to 31 * 37 mm. Enucleation was carried out in 14 patients, Whipple in 5, segmental resection in 3 and left distal pancreatectomy in 5 patients. The mortality rate was 0. Pathological findings were insulinoma or neuroendocrine tumors in 26 of 27 cases. One patient had a pathological finding of chronic pancreatic disease with intraepithelial neoplasia (grade 1A). CONCLUSION: We conclude that the preoperative localization of insulinoma in clinically suspected patients can be made on the basis of MRI and/or CT studies. A hallmark lesion is hypointense in T(1)-weighted sequences, homogeneously or peripherally hyperintense in T(1)-weighted fat-suppressed contrast-enhanced sequence using MRI (100% of cases) or/and a hypervascular enhanced lesion on arterial (100% of CT studies) and on venous series using CT (66.7% of CT studies). PMID- 22042213 TI - Theory and practice in the design and conduct of graduate medical education. AB - Medical education practice is more often the result of tradition, ritual, culture, and history than of any easily expressed theoretical or conceptual framework. The authors explain the importance and nature of the role of theory in the design and conduct of graduate medical education. They outline three groups of theories relevant to graduate medical education: bioscience theories, learning theories, and sociocultural theories. Bioscience theories are familiar to many medical educators but are often misperceived as truths rather than theories. Theories from such disciplines as neuroscience, kinesiology, and cognitive psychology offer insights into areas such as memory formation, motor skills acquisition, diagnostic decision making, and instructional design. Learning theories, primarily emerging from psychology and education, are also popular within medical education. Although widely employed, not all learning theories have robust evidence bases. Nonetheless, many important notions within medical education are derived from learning theories, including self-monitoring, legitimate peripheral participation, and simulation design enabling sustained deliberate practice. Sociocultural theories, which are common in the wider education literature but have been largely overlooked within medical education, are inherently concerned with contexts and systems and provide lenses that selectively highlight different aspects of medical education. They challenge educators to reconceptualize the goals of medical education, to illuminate maladaptive processes, and to untangle problems such as career choice, interprofessional communication, and the hidden curriculum.Theories make visible existing problems and enable educators to ask new and important questions. The authors encourage medical educators to gain greater understanding of theories that guide their educational practices. PMID- 22042214 TI - The history of calls for reform in graduate medical education and why we are still waiting for the right kind of change. AB - The author reviews the history of calls for reform of graduate medical education (GME), beginning with the Rappleye report of 1940, the first report on GME. Several continuities emerge. First, the reports have regularly called for GME to serve the "health needs of society." However, these perceived "needs" have continually been shifting as medicine and society evolve, thereby presenting GME a moving target. Second, the reports have regularly called for GME to focus more on education and less on service in order to avoid exploiting residents and compromising their training. Third, GME is a multifaceted subject. Reports on GME have typically addressed one part or another but not the subject as a whole. In their selectivity, the reports have reflected the particular perspective of the sponsoring groups. What the reports have generally not discussed, but what is underscored by calls for reform, is that GME is expensive, and any effort to improve its quality will be costly in terms of money, faculty time, or both. Thus, the profession has become complicit in maintaining the status quo. Any successful effort toward reform must acknowledge that GME functions as part of the larger health care delivery system, whose fate will ultimately determine the quality and robustness of GME in America. PMID- 22042215 TI - Statement of the American Society Of Addiction Medicine Consensus Panel on the use of buprenorphine in office-based treatment of opioid addiction. AB - OBJECTIVES: Opioid addiction affects over 2 million patients in the United States. The advent of buprenorphine and the passage of the Drug Addiction Treatment Act in 2000 have revolutionized the opioid treatment delivery system by granting physicians the ability to administer office-based opioid treatment (OBOT), thereby giving patients greater access to treatment. The purpose of this consensus panel was to synthesize the most current evidence on the use of buprenorphine in the office-based setting and to make recommendations that will enable and allow additional physicians to begin to treat opioid-addicted individuals. METHODS: Literature published from 2000 to 2009 was searched using the PubMed search engine and yielded over 375 articles published in peer-reviewed journals, including some that were published guidelines. These articles were submitted to a consensus panel composed of researchers, educators, and clinicians who are leaders in the field of addiction medicine with specific expertise in the use of OBOT. The panel discussed results and agreed upon consensus recommendations for several facets of OBOT. RESULTS: : On the basis of the literature review and consensus discussions, the panel developed a series of findings, conclusions, and recommendations regarding the use of buprenorphine in office-based treatment of opioid addiction. CONCLUSIONS: Therapeutic outcomes for patients who self-select office-based treatment with buprenorphine are essentially comparable to those seen in patients treated with methadone programs. There are few absolute contraindications to the use of buprenorphine, although the experience and skill levels of treating physicians can vary considerably, as can access to the resources needed to treat comorbid medical or psychiatric conditions--all of which affect outcomes. It is important to conduct a targeted assessment of every patient to confirm that the provider has resources available to meet the patient's needs. Patients should be assessed for a broad array of biopsychosocial needs in addition to opioid use and addiction, and should be treated, referred, or both for help in meeting all their care needs, including medical care, psychiatric care, and social assistance. Current literature demonstrates promising efficacy of buprenorphine, though further research will continue to demonstrate its effectiveness for special populations, such as adolescents, pregnant women, and other vulnerable populations. Since the time of this review, several new studies have provided new data to continue to improve our understanding of the safety and efficacy of buprenorphine for special patient populations. PMID- 22042216 TI - Understanding and treating comorbid anxiety disorders in substance users: review and future directions. AB - Anxiety disorders commonly occur among those with substance use disorders. This article reviews the literature describing the prevalence and patterns of this comorbidity in epidemiological and clinical samples and theoretical models explaining this comorbidity, and reviews the effects of anxiety disorders on substance use outcomes and data from clinical trials that target comorbid anxiety disorders to examine the effects of treating anxiety disorders on substance use outcomes. Next, this review outlines evidence-based pharmacological and psychological treatments for anxiety disorders and provides treatment recommendations for those treating this comorbid population. Finally, a discussion of treatment-delivery issues is presented to address the important issues that arise when treating anxiety disorders in typical addictions-treatment settings. PMID- 22042217 TI - Treatment of comorbid substance use and anxiety disorders: a case study. AB - This case study of combined anxiety with both alcohol and benzodiazepine dependence illustrates key issues in presentation, differential diagnosis and management. The case is discussed from a biopsychosocial perspective with each of the discussants focusing on their particular area of experience and expertise, then the treatment package is presented in an integrated fashion. Of particular interest is how social anxiety disorder may become a significant barrier to engagement and retention, and thus outcome in persons presenting for addiction treatment, and how a treatment plan for such patients can be built. PMID- 22042218 TI - Tautomerism in Schiff bases. The cases of 2-hydroxy-1-naphthaldehyde and 1 hydroxy-2-naphthaldehyde investigated in solution and the solid state. AB - Schiff bases derived from hydroxyl naphthaldehydes and o-substituted anilines have been prepared and their tautomerism assessed by spectroscopic, crystallographic, and computational methods. Tautomeric equilibria have also been studied and reveal in most cases a slight preference of imine tautomers in solution; a fact supported by DFT calculations in the gas phase as well as incorporating solvent effects through the SMD model. To simulate the effect exerted by the crystal lattice on tautomer stability, we have developed a computational protocol in the case of 1-tert-butyl-2-(2-hydroxy-1 naphthylmethylene)aminobenzene whose data have been obtained experimentally at 120 K. Although a rapid imine-enamine interconversion may be occurring in the solid state, the imine tautomer becomes the most stable form and the energy difference should be related to the difference in the packing of the molecules. PMID- 22042219 TI - Molecular imaging for stem cell transplantation in neuroregenerative medicine. AB - Stem cell transplantation is a promising new therapeutic option in different neurological diseases. However, it was not yet possible to translate its potential from animal models to clinical application. One of the main problems of applying stem cell transplantation in clinical medium is the difficulty of detection, localization, and examination of the stem cells in vivo at both cellular and molecular levels. State-of-the-art molecular imaging techniques provide new and better means for noninvasive, repeated, and quantitative tracking of stem cell implant or transplant. From initial deposition to the survival, migration, and differentiation of the transplant/implanted stem cells, current molecular imaging methods allow monitoring of the infused cells in the same live recipient over time. The present review briefly summarizes and compares these molecular imaging methods for cell labeling and imaging in animal models as well as in clinical application and sheds light on consecutive new therapeutic options if appropriate. PMID- 22042220 TI - Cannabis use patterns and their association with DSM-IV cannabis dependence and gender. AB - AIMS: To investigate the gender differences in the patterns of cannabis use (CU), namely frequency, times of day, social context and methods and in their association with DSM-IV cannabis dependence. METHODS: A sample of 3,904 students from German universities was recruited via an internet survey. Logistic regressions and associated areas under the ROC curve (AUC) were calculated among current cannabis users (at least once a month, n = 843). RESULTS: CU using a water pipe was more often reported by males (50 vs. 34.6%). Usual CU 'before going to sleep at night' was more often reported by females (47.3 vs. 35.7%). Most CU patterns showed a similar association with DSM-IV cannabis dependence in both genders. The association of CU 'with strangers' was stronger in females (AUC 0.68 vs. AUC 0.56). Slightly different multiple models were found (females AUC 0.86, males AUC 0.77). CONCLUSIONS: There are considerable gender differences in the CU patterns and, thus, in the way CU functions. In the association of CU patterns with cannabis dependence, the similarities are rather great. Examining the CU patterns might make a considerable contribution to the better detection of high-risk population segments for prevention and early intervention in both genders. PMID- 22042221 TI - Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. AB - Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors is the crucial mechanism underlying the suppressive GC effect. Here we demonstrate that mice with a dimerization deficient GR (GR(dim)) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)-induced septic shock. TNF-alpha is normally regulated in these mice, but down-regulation of IL-6 and IL-1beta is diminished. LPS-treated macrophages derived from GR(dim) mice are largely resistant to GC actions in vitro in terms of morphology, surface marker expression, and gene expression. Treatment with recombinant IL-1 receptor antagonist improved survival of GR(dim) mice and mice lacking the GR in macrophages (GR(LysMCre)) mice. This suggests that regulation of IL-1beta in macrophages by GCs is pivotal to control sepsis. PMID- 22042222 TI - Activated platelets contribute to oxidized low-density lipoproteins and dysfunctional high-density lipoproteins through a phospholipase A2-dependent mechanism. AB - Plasma activity of secretory phospholipase A2 (sPLA2) increases in patients with cardiovascular disease. The present study investigated whether platelet-released sPLA2 induces low-density lipoprotein (LDL) and high-density lipoprotein (HDL) modifications that translate into changes in lipoprotein function. Activated but not resting platelets induced oxidative modifications of human native LDLs and HDLs, which render these particles dysfunctional. Platelet-incubated LDLs stimulated the incorporation of cholesterol oleate into macrophages, and modified HDLs lost their cholesterol efflux capacity and antioxidant properties. In vitro and ex vivo experiments showed that lysophophatidylcholine accumulated in the platelet-modified LDLs and HDLs of mice expressing sPLA2 (Balb/c and transgenic C57Bl/6 mice expressing human sPLA2) but not in the lipoproteins of naturally sPLA2-deficient mice (C57Bl/6). Unlike C57Bl/6 mice, Balb/c mice injected with leptin (67 MUg/mouse, i.p.) as an in vivo prothrombotic agent displayed increased plasma sPLA2 activity, reduced clotting time, higher plasma levels of oxidation products, increased production of nonesterified fatty acids, and more substantial platelet-mediated modification of lipoproteins. These effects were blocked completely by injection of the platelet inhibitor ticlopidine (5 mg/kg, i.p.) or by a sPLA2 inhibitor (LY311727, 3 mg/kg, i.p.). These results demonstrate that stimulated platelets are major contributors to plasma sPLA2 activity in vivo and account to a large extent for the adverse modification of circulating lipoproteins. PMID- 22042223 TI - Autocrine abscisic acid plays a key role in quartz-induced macrophage activation. AB - Inhalation of quartz induces silicosis, a lung disease where alveolar macrophages release inflammatory mediators, including prostaglandin-E(2) (PGE(2)) and tumor necrosis factor alpha (TNF-alpha). Here we report the pivotal role of abscisic acid (ABA), a recently discovered human inflammatory hormone, in silica-induced activation of murine RAW264.7 macrophages and of rat alveolar macrophages (AMs). Stimulation of both RAW264.7 cells and AMs with quartz induced a significant increase of ABA release (5- and 10-fold, respectively), compared to untreated cells. In RAW264.7 cells, autocrine ABA released after quartz stimulation sequentially activates the plasma membrane receptor LANCL2 and NADPH oxidase, generating a Ca(2+) influx resulting in NFkappa B nuclear translocation and PGE(2) and TNF-alpha release (3-, 2-, and 3.5-fold increase, respectively, compared to control, unstimulated cells). Quartz-stimulated RAW264.7 cells silenced for LANCL2 or preincubated with a monoclonal antibody against ABA show an almost complete inhibition of NFkappa B nuclear translocation and PGE(2) and TNF-alpha release compared to controls electroporated with a scramble oligonucleotide or preincubated with an unrelated antibody. AMs showed similar early and late ABA-induced responses as RAW264.7 cells. These findings identify ABA and LANCL2 as key mediators in quartz-induced inflammation, providing possible new targets for antisilicotic therapy. PMID- 22042224 TI - Inhibition of TLR2 promotes graft function in a murine model of renal transplant ischemia-reperfusion injury. AB - Toll-like receptors (TLRs) are important molecules involved in the activation of innate and subsequent development of adaptive immunity. TLRs are ligated by exogenous ligands from pathogens and by endogenous ligands released in inflammatory diseases. Activation of TLR leads to activation of NF-kappaB and release of proinflammatory cytokines, such as IL-6 and TNF-alpha. TLRs play an important role in the pathogenesis of renal diseases. Increased expression of TLRs have been associated with ischemic kidney damage, acute kidney injury, end stage renal failure, acute renal transplant rejection, and delayed allograft function. OPN301 is a mouse anti-human TLR2 antibody that cross-reacts with mouse TLR2. We show that inhibition of TLR2 promotes graft function in an isograft model of renal transplantation. Recipient mice were treated intravenously with OPN301 before reperfusion of the transplanted kidney that had been subjected to 30 min of cold ischemia. After 5 d, the residual native kidney was removed, and renal transplant function was assessed 24 h later by measurement of blood urea nitrogen. Renal function in both saline- and isotype-treated mice was similar, with significant improvement in OPN301-treated mice (isotype-treated vs. OPN301 treated: 33.9+/-3.2 vs. 19.8+/-1.9 MUM; P<0.01). The histopathological appearance corresponded with renal functional results. In OPN301-treated recipients, renal structure was well preserved, whereas in the saline-treated group, tubular injury was severe, with marked tubular thinning, epithelial shedding, cast formation and necrosis. Inhibition of TLR2 also leads to a decrease in C3d deposition, although it is unclear whether this is due directly to TLR2 inhibition or a decrease in renal inflammation. This study shows that inhibition of TLR2 with a therapeutic agent (OPN301) provides significant protection from ischemia/reperfusion injury in a model of kidney transplantation. PMID- 22042225 TI - Managing Cancer and Living Meaningfully (CALM): a qualitative study of a brief individual psychotherapy for individuals with advanced cancer. AB - BACKGROUND: Although psychosocial care has been regarded as central to palliative and supportive care, there have been few empirically tested approaches to individual intervention. AIM: The subjective experience of advanced cancer patients receiving a new manualized brief individual psychotherapy, referred to as Managing Cancer and Living Meaningfully (CALM), was examined prior to the initiation of a randomized controlled trial testing the effectiveness of this intervention. DESIGN: Semi-structured interviews were conducted with patients who had a diagnosis of advanced cancer, and who underwent the intervention. SETTING/PARTICIPANTS: Patients were recruited from a large urban regional cancer center in Toronto, Canada. The 10 interviewees included seven women and three men. All had completed between three to six CALM sessions prior to the interview. RESULTS: The CALM intervention was associated with profound and unique patient identified benefits and no patient-identified risks or concerns. Five interrelated benefits of the intervention were identified: (1) a safe place to process the experience of advanced cancer; (2) permission to talk about death and dying; (3) assistance in managing the illness and navigating the healthcare system; (4) resolution of relational strain; and (5) an opportunity to 'be seen as a whole person' within the healthcare system. These benefits were regarded by participants as unique in their cancer journey. CONCLUSIONS: Findings from a qualitative study suggest that the CALM intervention provides substantial benefits for patients with advanced cancer prior to the end of life. Findings informed the development of a randomized controlled trial to evaluate the effectiveness of this intervention. PMID- 22042226 TI - Feeling severely affected by multiple sclerosis: what does this mean? AB - BACKGROUND: The situation for people feeling severely affected by Multiple Sclerosis (MS) remains largely unexamined and the term 'severe MS' is not clearly defined. AIM: Our study describes this sub-group of patients utilizing exclusively a subjective inclusion criterion to analyse their reasons for feeling severely affected and document their perceived unmet needs. DESIGN: A questionnaire with open- and closed-ended items addressing only patients feeling severely affected was sent out nationwide. Expanded Disability Status Score (EDSS) and subjectively severe affectedness were analysed for correlation. After dichotomizing both scores by a median split, the answers were allocated to these groups and tested for significant differences. SETTING/PARTICIPANTS: 1,110 questionnaires were analysed regarding the closed-ended questions while a subsample of 40% (n = 445) was analysed regarding the open-ended questions. Average age of participants was 51.87 years. Average time since diagnosis was 16.6 years. Main course of the disease was secondary progressive (35.5%). RESULTS: The most frequently mentioned reasons for feeling severely affected were lack of mobility (56.4%) and fatigue (27.4%). Significant percentages for unmet needs were seen in the categories of funding services (31.0%), better social integration (24.7%) and medical support (25.2%). A significant correlation was observed between EDSS and subjectively felt affectedness (p <= 0.01). Motor disorders explained differences in patient needs behind a higher EDSS score; higher severe affectedness referred to other issues like dependency and immobility. CONCLUSIONS: EDSS is insufficient for usage as the sole instrument for measuring severe affectedness as it does not take into account other potential reasons. Complex patient needs necessitate multi-professional care as offered by palliative medicine. PMID- 22042227 TI - BACE1 in central nervous system myelination revisited. PMID- 22042229 TI - Communication breakdown: delta-9 tetrahydrocannabinol effects on pre-speech neural coherence. PMID- 22042228 TI - Genome-wide association analysis of copy number variation in recurrent depressive disorder. AB - Large, rare copy number variants (CNVs) have been implicated in a variety of psychiatric disorders, but the role of CNVs in recurrent depression is unclear. We performed a genome-wide analysis of large, rare CNVs in 3106 cases of recurrent depression, 459 controls screened for lifetime-absence of psychiatric disorder and 5619 unscreened controls from phase 2 of the Wellcome Trust Case Control Consortium (WTCCC2). We compared the frequency of cases with CNVs against the frequency observed in each control group, analysing CNVs over the whole genome, genic, intergenic, intronic and exonic regions. We found that deletion CNVs were associated with recurrent depression, whereas duplications were not. The effect was significant when comparing cases with WTCCC2 controls (P=7.7 * 10( 6), odds ratio (OR) =1.25 (95% confidence interval (CI) 1.13-1.37)) and to screened controls (P=5.6 * 10(-4), OR=1.52 (95% CI 1.20-1.93). Further analysis showed that CNVs deleting protein coding regions were largely responsible for the association. Within an analysis of regions previously implicated in schizophrenia, we found an overall enrichment of CNVs in our cases when compared with screened controls (P=0.019). We observe an ordered increase of samples with deletion CNVs, with the lowest proportion seen in screened controls, the next highest in unscreened controls and the highest in cases. This may suggest that the absence of deletion CNVs, especially in genes, is associated with resilience to recurrent depression. PMID- 22042230 TI - DNA methylation: bisulphite modification and analysis. AB - Epigenetics describes the heritable changes in gene function that occur independently to the DNA sequence. The molecular basis of epigenetic gene regulation is complex, but essentially involves modifications to the DNA itself or the proteins with which DNA associates. The predominant epigenetic modification of DNA in mammalian genomes is methylation of cytosine nucleotides (5-MeC). DNA methylation provides instruction to gene expression machinery as to where and when the gene should be expressed. The primary target sequence for DNA methylation in mammals is 5'-CpG-3' dinucleotides (Figure 1). CpG dinucleotides are not uniformly distributed throughout the genome, but are concentrated in regions of repetitive genomic sequences and CpG "islands" commonly associated with gene promoters (Figure 1). DNA methylation patterns are established early in development, modulated during tissue specific differentiation and disrupted in many disease states including cancer. To understand the biological role of DNA methylation and its role in human disease, precise, efficient and reproducible methods are required to detect and quantify individual 5-MeCs. This protocol for bisulphite conversion is the "gold standard" for DNA methylation analysis and facilitates identification and quantification of DNA methylation at single nucleotide resolution. The chemistry of cytosine deamination by sodium bisulphite involves three steps (Figure 2). (1) Sulphonation: The addition of bisulphite to the 5-6 double bond of cytosine (2) Hydrolic Deamination: hydrolytic deamination of the resulting cytosine-bisulphite derivative to give a uracil-bisulphite derivative (3) Alkali Desulphonation: Removal of the sulphonate group by an alkali treatment, to give uracil. Bisulphite preferentially deaminates cytosine to uracil in single stranded DNA, whereas 5-MeC, is refractory to bisulphite mediated deamination. Upon PCR amplification, uracil is amplified as thymine while 5-MeC residues remain as cytosines, allowing methylated CpGs to be distinguished from unmethylated CpGs by presence of a cytosine "C" versus thymine "T" residue during sequencing. DNA modification by bisulphite conversion is a well-established protocol that can be exploited for many methods of DNA methylation analysis. Since the detection of 5-MeC by bisulphite conversion was first demonstrated by Frommer et al. and Clark et al., methods based around bisulphite conversion of genomic DNA account for the majority of new data on DNA methylation. Different methods of post PCR analysis may be utilized, depending on the degree of specificity and resolution of methylation required. Cloning and sequencing is still the most readily available method that can give single nucleotide resolution for methylation across the DNA molecule. PMID- 22042231 TI - Characterization of a recombinant aryl beta-glucosidase from Neosartorya fischeri NRRL181. AB - An isolated gene from Neosartorya fischeri NRRL181 encoding a beta-glucosidase (BGL) was cloned, and its nucleotide sequence was determined. DNA sequence analysis revealed an open reading frame of 1,467 bp, capable of encoding a polypeptide of 488 amino acid residues. The gene was over-expressed in Escherichia coli, and the protein was purified using nickel-nitrilotriacetic acid chromatography. The purified recombinant BGL showed a high level of catalytic activity, with V (max) of 886 MUmol min(-1) mg-protein(-1) and a K (m) of 68 mM for p-nitrophenyl-beta-D: -glucopyranoside (pNPG). The optimal temperature for enzyme activity was about 40 degrees C, and the optimal pH was about 6.0. A homology model of N. fischeri BGL1 was constructed based on the X-ray crystal structure of Phanerochaete chrysosporium BGLA. Molecular dynamics simulation studies of the enzyme with the pNPG and cellobiose shed light on the unique substrate specificity of N. fischeri BGL1 only towards pNPG. PMID- 22042232 TI - Rapid detection of rRNA group I pseudomonads in contaminated metalworking fluids and biofilm formation by fluorescent in situ hybridization. AB - Metalworking fluids (MWFs), used in different machining operations, are highly prone to microbial degradation. Microbial communities present in MWFs lead to biofilm formation in the MWF systems, which act as a continuous source of contamination. Species of rRNA group I Pseudomonas dominate in contaminated MWFs. However, their actual distribution is typically underestimated when using standard culturing techniques as most fail to grow on the commonly used Pseudomonas Isolation Agar. To overcome this, fluorescent in situ hybridization (FISH) was used to study their abundance along with biofilm formation by two species recovered from MWFs, Pseudomonas fluorescens MWF-1 and the newly described Pseudomonas oleovorans subsp. lubricantis. Based on 16S rRNA sequences, a unique fluorescent molecular probe (Pseudo120) was designed targeting a conserved signature sequence common to all rRNA group I Pseudomonas. The specificity of the probe was evaluated using hybridization experiments with whole cells of different Pseudomonas species. The probe's sensitivity was determined to be 10(3) cells/ml. It successfully detected and enumerated the abundance and distribution of Pseudomonas indicating levels between 3.2 (+/- 1.1) * 10(6) and 5.0 (+/- 2.3) * 10(6) cells/ml in four different industrial MWF samples collected from three different locations. Biofilm formation was visualized under stagnant conditions using high and low concentrations of cells for both P. fluorescens MWF 1 and P. oleovorans subsp. lubricantis stained with methylene blue and Pseudo120. On the basis of these observations, this molecular probe can be successfully be used in the management of MWF systems to monitor the levels and biofilm formation of rRNA group I pseudomonads. PMID- 22042233 TI - Topical TRPM8 agonist (icilin) relieved vulva pruritus originating from lichen sclerosus et atrophicus. PMID- 22042235 TI - The effect of varying carboxylate ligation on the electronic environment of N2O(x) (x = 1-3) nonheme iron: a DFT analysis. AB - Mononuclear nonheme iron oxygenase (MNO) enzymes contain a subclass of metalloproteins capable of catalyzing the O(2)-dependent hydroxylation of unactivated substrates at a ferrous ion center coordinated to a highly conserved His-His-Glu/Asp motif. These enzymes, which utilize additional reducing equivalents obtained from the decarboxylation of a coordinated alpha ketoglutarate (alphaKG) cofactor, do not readily interact with O(2) in the absence of alphaKG binding. Density functional theory calculations with the B3LYP functional were performed to gain insight into the electrochemical behavior of three sets of Fe(II/III) complexes containing a core N, N, O facial binding motif in which the number of carboxylate ligands was systematically altered, to provide one, two (cis) or three (fac) labile sites. The calculated trend in Fe(II/III) reduction potentials was observed to parallel that observed in cyclic voltammetry experiments, showing a decrease in potential (stabilized oxidized state) with increasing carboxylate ligation. This trend does not appear to be the result of differential charge on the metal complex. Changes in the redox-active molecular orbital (RAMO) energy due to covalent effects dominate across the series of complexes when chloride is modeled as the labile ligand, with the pi anti-bonding nature of the RAMO being an important factor. With water molecules as the labile ligands, however, a much steeper redox dependence on the number of carboxylate ligands is observed and this effect seems to be largely electrostatic in origin. Differential relaxation of the occupied molecular orbitals in the ferric complexes appears to contribute to the redox trend as well. Finally, these observations are placed in the context of MNO enzyme mechanisms. PMID- 22042234 TI - Externalizing behaviors are associated with SNPs in the CHRNA5/CHRNA3/CHRNB4 gene cluster. AB - There is strong evidence for shared genetic factors contributing to childhood externalizing disorders and substance abuse. Externalizing disorders often precede early substance experimentation, leading to the idea that individuals inherit a genetic vulnerability to generalized disinhibitory psychopathology. Genetic variation in the CHRNA5/CHRNA3/CHRNB4 gene cluster has been associated with early substance experimentation, nicotine dependence, and other drug behaviors. This study examines whether the CHRNA5/CHRNA3/CHRNB4 locus is correlated also with externalizing behaviors in three independent longitudinally assessed adolescent samples. We developed a common externalizing behavior phenotype from the available measures in the three samples, and tested for association with 10 SNPs in the gene cluster. Significant results were detected in two of the samples, including rs8040868, which remained significant after controlling for smoking quantity. These results expand on previous work focused mainly on drug behaviors, and support the hypothesis that variation in the CHRNA5/CHRNA3/CHRNB4 locus is associated with early externalizing behaviors. PMID- 22042236 TI - Volume and attenuation computed tomography measurements for interim evaluation of Hodgkin and follicular lymphoma as an additional surrogate parameter for more confident response monitoring: a pilot study. AB - PURPOSE: To retrospectively determine the potential role of additional computed tomography (CT) attenuation measurements for interim response evaluation in residual masses of patients with Hodgkin disease (HD) and follicular non-Hodgkin lymphoma (NHL). MATERIALS AND METHODS: In this retrospective study, 39 patients with HD and 35 patients with NHL presented with residual masses at mid-treatment CT (after 2-4 cycles of chemotherapy) and were assessed via contrast-enhanced CT at baseline, mid-treatment and post-treatment. Volume was recorded as whole tumour volume. A tumour attenuation ratio (TAR) was calculated as the quotient of attenuation between tumour and muscle at the respective point in time versus baseline. The standard deviation of attenuation values within the tumour volume was recorded to estimate tumour heterogeneity. Results were correlated with relapse-free survival determined at a minimum of 12 months after end-treatment CT. RESULTS: Tumour volume and TAR at interim versus baseline control were significantly reduced in responders compared with non-responders, even after controlling for age, stage, treatment regimen, and baseline tumour volume. No significant differences with respect to the standard deviation of attenuation values within the tumour volumes (tumour heterogeneity) were observed. The volume and attenuation CT (VACT) criteria yielded the highest sensitivities and specificities for the identification of non-response at a threshold of a >20% increase in volume and an increase in TAR at interim control, i.e. 88% (NHL 80%, HD 100%) and 98% (NHL 97%, HD 100%), respectively. The negative predictive values reached by VACT analysis were >=97%, according to both parameters. CONCLUSION: Mid-treatment response assessment of residual masses in patients with HD and NHL using VACT may aid in the risk stratification as an additional surrogate parameter. PMID- 22042237 TI - Anti-inflammatory activity of chondroitin sulphate: new functions from an old natural macromolecule. AB - Chondroitin sulphate (CS) is recommended by the European League Against Rheumatism as a symptomatic slow-acting drug for the treatment of osteoarthritis on the basis of numerous clinical trials and meta-analyses. Furthermore, recent clinical trials have also demonstrated the possible structure-modifying effects of CS. This review focuses on recent experimental results and data available in the scientific literature regarding the anti-inflammatory properties of CS with a view to understanding the molecular basis responsible for its activity. Several animal studies have demonstrated that orally administered CS significantly inhibited hind paw oedema, synovitis and destruction of the articular cartilage in a dose-dependent manner. Furthermore, CS proved to have a beneficial effect in slowing down the development of adjuvant arthritis and in reducing disease markers, findings which support its beneficial activity in humans as a chondroprotective drug. Finally, several in vitro studies have focused on the hypothesis that CS may reduce inflammatory processes by acting on the nuclear translocation of NF-kappaB, which is closely associated with the blood biomarkers of inflammation, primarily IL-1, IL-6 and C-reactive protein. PMID- 22042238 TI - Burn wound mucormycosis: a case report. PMID- 22042239 TI - Clinical characteristics and comparative study of different modalities of treatment of pseudocyst pinna. AB - The aims of the article were to study the clinical characteristic of patients with pseudocysts and to compare different common modalities of treatment and introduce the concept of observation in pseudocyst management. Twenty-eight patients were diagnosed with pseudocyst of the auricle between June 2009 and June 2011 in a medical college hospital. The patients were divided into four groups each of seven patients on the basis of primary treatment offered. Four primary treatments offered were simple aspiration, aspiration with intralesional steroid, incision and drainage with removal of anterior cartilage leaflet with buttoning, and lastly, simple observation and reassurance. All 28 patients were male with involvement of right side more than left and no one had bilateral involvement. Adults in the age group of 30-40 were commonly affected. Most of the patients had history of significant trauma by security forces. Most common site of involvement was scaphoid and triangular fossa. The best form of treatment with minimum recurrence was incision and drainage with removal of anterior cartilage leaflet with buttoning. Simple observation as a treatment option was found to be as good as intralesional steroids. Pseudocyst of the pinna is a benign condition of unknown etiology affecting the pinna, commonly encountered in middle-aged men. It is a rare condition and is hardly encountered in routine ENT practice. Bilateral diseases are uncommon. Most common site of occurrence is triangular and scaphoid fossa. Many modalities of treatment have been recommended in literature with varied recurrence and failure rates. The best treatment is surgical deroofing followed by buttoning with minimum recurrences. An option of simple observation for 2-3 months should be discussed with each patient and was found to be as good as intralesional steroids. PMID- 22042240 TI - Evaluation of nodal response after intra-arterial chemoradiation for node positive head and neck cancer. AB - This retrospective study aimed to compare the accuracy of two nodal evaluation criteria using computed tomography after intra-arterial chemoradiation in node positive head and neck squamous cell carcinomas. Computed tomography was used to evaluate radiographic nodal response 4-8 weeks after intra-arterial chemoradiation. We compared the accuracy of two different criteria: criterion 1 (radiographic complete response was recorded in the absence of focal abnormalities and if the maximum diameter of the metastatic node was less than 15 mm), and criterion 2 (radiographic complete response was recorded in the absence of focal abnormalities and if the minimum diameter of metastatic nodes was less than 7 mm in level II and if the minimum diameter of metastatic nodes in the rest of the neck was less than 6 mm). Positive predictive values were criterion 1: 69.2%, criterion 2: 47.8%; negative predictive values were criterion 1: 88.5%, criterion 2: 90.5%. Positive likelihood ratios were criterion 1: 7.50, criterion 2: 3.06. The difference between each criteria was statistically significant using McNemar's test (p = 0.0016). Computed tomography evaluation accuracy of nodal response after intra-arterial chemoradiation was comparable to recent reports, and it was feasible to perform salvage neck dissection by computed tomography evaluation for nodal response. We recommend using criterion 1 because of its simplicity and reliability. PMID- 22042241 TI - Postoperative complications in cochlear implants: a retrospective analysis of 438 consecutive cases. AB - Our objective is to determine the complication rate in a population of infants, children, adolescents and adults, from a University Hospital Cochlear Implant program and to discuss their causes and treatments. The methods include a retrospective study of 438 consecutive patients in a tertiary referral centre, the Audiology Department of the University Hospital of Ferrara. All patients receiving cochlear implants, between 1 January 2003 and 31 December 2009, have been included. All complications and treatments were systematically reviewed with an average duration of follow-up of 46 months (range 10-84 months). The results reveal that the overall rate of complications in our group was 9.1% (40 of 438), and most of them were minor. Wound swelling and infections represent the most common complication occurred. There were no cases of transient or permanent facial palsy following surgery, and also we did not register any case of postsurgical meningitis. Thirteen patients (3.0%) underwent explantation followed by reimplantation. In conclusion, we find that Cochlear implantation is a safe low-morbility technique with a relatively low complication rate in the presented population. PMID- 22042242 TI - Olfactory function in patients with ischemic stroke: a pilot study. AB - The aim of this pilot study was to investigate olfactory function in unselected, cooperative patients with ischemic stroke and to gain information about olfactory perception in patients with distinct stroke localizations. Three ischemic stroke patients underwent olfactory testing using the Sniffin' Sticks test and olfactory event-related potentials recording. All stroke patients were found to be normosmic or only slightly hyposmic when using a psychophysical testing device with age-adjusted norms. No responses or longer latencies on the affected side were found, however, when recording evoked potentials. This seems to argue for the idea that on the affected side it is often possible to document the objective lesion although the subjective perception of the patient appears normal. PMID- 22042243 TI - Practical diagnosis of red cell disorders in southern Spain. AB - BACKGROUND: Hereditary red cell disorders are associated with a protective effect against malaria, which results in an increased prevalence in malaria-endemic areas. Migratory flows from these areas are resulting in a marked increase in such abnormalities in Southern Spain. METHODS: All hemoglobin disorders diagnosed between 1997 and 2010 have been recorded. Since 2008, we have performed systematic screening for hemoglobinopathies on African patients. A high-pressure liquid chromatography system was used as screening method for structural hemoglobinopathies and for separation of hemoglobin (Hb) F and A(2). RESULTS: We detected 666 cases in patients of foreign origin and 308 in native Spanish patients. Thalassemias (thal) are the most frequent disorders amongst the local population: beta-thal minor, 57.1% (176/308); alpha-thal, 18.2% (56/308), and deltabeta-thal, 7.8% (24/308). In ethnic minorities, there is a huge variety of hemoglobinopathies: heterozygous Hb S, 45% (300/666); heterozygous Hb C, 15% (100/666); beta-thal minor, 13.7% (91/666); alpha-thal, 10.2% (68/666); Hb SS in 14 patients, and Hb CC in 9 patients. Of the native patients, 14 were found to have Hb AS and 9 Hb AC. CONCLUSION: Given the modern migratory flows, greater knowledge of these disorders is needed by all medical staff, and new practical and cost/time-effective diagnostic approaches have to be devised. PMID- 22042244 TI - Mucinous cystic neoplasms of the pancreas: definition of preoperative imaging criteria for high-risk lesions. AB - BACKGROUND/AIM: Pancreatic mucinous cystic neoplasms (MCN) are premalignant lesions whose natural history is poorly known. Whether the dysplasia grade might be determined with precision by preoperative clinical and imaging criteria is not known. We aimed to determine if CT scan data might be useful to predict the grade of dysplasia in a series of 60 histologically proven MCN. METHODS: All consecutive patients who were operated on with pathological confirmation of MCN were included. Careful CT scan evaluation was reviewed without knowledge of pathological results. Imaging and pathological results were correlated. RESULTS: Sixty patients (59 females) were included. Low- and intermediate-grade dysplasias were identified in 47 and 3 patients (benign MCN), respectively, and high-grade dysplasia and invasive carcinoma in 7 and 3 patients (malignant MCN), respectively. Patients with benign lesions were significantly younger. None of the studied clinical data were statistically different to distinguish benign and malignant MCN, except age (42 vs. 48 years, p < 0.05). Only maximal diameter and mural nodules on CT scan were significantly more frequent in the malignant group. No malignant MCN had a maximal diameter <40 mm. At a 40-mm threshold, the sensitivity and specificity of the maximal diameter to diagnose malignant MCN were 100 and 54%, respectively. Mural nodules seen on CT scan were confirmed in all cases but one upon pathological examination of the surgical specimen. The sensitivity and specificity of the presence of a mural nodule seen on CT scan for the diagnosis of a malignant lesion were 100 and 98%, respectively. CONCLUSION: Preoperative CT scan detection of a mural nodule within a cystic pancreatic neoplasm suggestive of MCN strongly suggests malignancy. A diameter <40 mm is associated with no risk of malignancy. PMID- 22042245 TI - Chromatographic purification of highly active yeast ribosomes. AB - Eukaryotic ribosomes are much more labile as compared to their eubacterial and archael counterparts, thus posing a significant challenge to researchers. Particularly troublesome is the fact that lysis of cells releases a large number of proteases and nucleases which can degrade ribosomes. Thus, it is important to separate ribosomes from these enzymes as quickly as possible. Unfortunately, conventional differential ultracentrifugation methods leaves ribosomes exposed to these enzymes for unacceptably long periods of time, impacting their structural integrity and functionality. To address this problem, we utilize a chromatographic method using a cysteine charged Sulfolink resin. This simple and rapid application significantly reduces co-purifying proteolytic and nucleolytic activities, producing high yields of intact, highly biochemically active yeast ribosomes. We suggest that this method should also be applicable to mammalian ribosomes. The simplicity of the method, and the enhanced purity and activity of chromatographically purified ribosome represents a significant technical advancement for the study of eukaryotic ribosomes. PMID- 22042246 TI - A new cyclopamine glucuronide prodrug with improved kinetics of drug release. AB - We prepared a new glucuronide prodrug of cyclopamine designed to target selectively the Hedgehog signalling pathway of cancer cells. This prodrug includes a novel self-immolative linker bearing a hydrophilic side chain that can be easily introduced via"click chemistry". With this design, the prodrug exhibits reduced toxicity compared to the free drug on U87 glioblastoma cells. However, in the presence of beta-glucuronidase, the prodrug conducts to the quick release of cyclopamine thereby restoring its antiproliferative activity. PMID- 22042247 TI - Response to cutaneous immunization with low-molecular-weight subunit keyhole limpet hemocyanin. AB - BACKGROUND: This study was carried out to determine whether humoral and cellular immune responses would be provoked by cutaneous administration of keyhole limpet hemocyanin (KLH) and in particular by scarification of the skin (SS). METHODS: This was an unblinded, single-center, 8-week pilot study in healthy young adults. Twenty-four subjects assigned to 4 groups completed the study. Each group was immunized twice, with a 3-week interval, either by SS or intradermally (ID), with an SS dose of 50 or 250 MUg and an ID dose of 100 or 250 MUg. Serum was collected for antibody assays at baseline and 3 weeks after both the first and second immunizations. Delayed-type hypersensitivity (DTH) testing was performed before the first immunization and 3 weeks after the second. RESULTS: In the 250-MUg SS group, there was a significant increase from day 0 to day 47 in anti-KLH IgG (p = 0.02; day 0: 3.46 +/- 5.49 mg/dl, day 47: 7.54 +/- 8.87 mg/dl) and anti-KLH IgA (p = 0.04; day 0: 4.78 +/- 9.15 mg/dl, day 47: 11.42 +/- 13.62 mg/dl). One subject in each treatment group showed a positive DTH test result representing 20% (50-MUg SS), 10% (250-MUg SS), 25% (100-MUg ID) and 20% (250-MUg ID) of the subjects. CONCLUSIONS: It was possible to induce both humoral and cellular immune responses by SS administration despite the limited antigenic potency of the low molecular-weight KLH preparation. This approach may be useful for studying the mechanisms of immune response in allergic skin diseases such as atopic dermatitis. PMID- 22042249 TI - One-pot, single-component synthesis of functional emulsion-templated hybrid inorganic-organic polymer capsules. AB - Multi-purpose amphiphilic branched copolymer surfactants can be used to simultaneously stabilise and cross-link emulsion droplets to produce encapsulated spheres and hollow capsules. PMID- 22042248 TI - Abnormal microRNA expression in Ts65Dn hippocampus and whole blood: contributions to Down syndrome phenotypes. AB - Down syndrome (DS; trisomy 21) is one of the most common genetic causes of intellectual disability, which is attributed to triplication of genes located on chromosome 21. Elevated levels of several microRNAs (miRNAs) located on chromosome 21 have been reported in human DS heart and brain tissues. The Ts65Dn mouse model is the most investigated DS model with a triplicated segment of mouse chromosome 16 harboring genes orthologous to those on human chromosome 21. Using ABI TaqMan miRNA arrays, we found a set of miRNAs that were significantly up- or downregulated in the Ts65Dn hippocampus compared to euploid controls. Furthermore, miR-155 and miR-802 showed significant overexpression in the Ts65Dn hippocampus, thereby confirming results of previous studies. Interestingly, miR 155 and miR-802 were also overexpressed in the Ts65Dn whole blood but not in lung tissue. We also found overexpression of the miR-155 precursors, pri- and pre-miR 155 derived from the miR-155 host gene, known as B cell integration cluster, suggesting enhanced biogenesis of miR-155. Bioinformatic analysis revealed that neurodevelopment, differentiation of neuroglia, apoptosis, cell cycle, and signaling pathways including ERK/MAPK, protein kinase C, phosphatidylinositol 3 kinase, m-TOR and calcium signaling are likely targets of these miRNAs. We selected some of these potential gene targets and found downregulation of mRNA encoding Ship1, Mecp2 and Ezh2 in Ts65Dn hippocampus. Interestingly, the miR-155 target gene Ship1 (inositol phosphatase) was also downregulated in Ts65Dn whole blood but not in lung tissue. Our findings provide insights into miRNA-mediated gene regulation in Ts65Dn mice and their potential contribution to impaired hippocampal synaptic plasticity and neurogenesis, as well as hemopoietic abnormalities observed in DS. PMID- 22042250 TI - Association between leptin levels and doses of clomethiazole during alcohol withdrawal: a pilot study. AB - AIMS: The issue of leptin as a putative state marker of alcohol use and its role in craving has been raised in the last few years. Recently, a strong GABA-ergic modulation of leptin was postulated. The aim of the pilot study was to examine leptin levels in correlation with the strongly GABA-mimetic active substance clomethiazole. The main hypothesis was that higher doses of the strong GABA mimetic clomethiazole are positively correlated with higher leptin levels. METHODS: Twenty-eight alcohol-dependent patients (3 females, median age 36 years) undergoing alcohol withdrawal were included. In 18 patients with and 10 without clomethiazole, serum leptin was analyzed at day 1 and day 7 of alcohol withdrawal. Both groups did not differ by age, BMI, or alcohol use characteristics. RESULTS: In the clomethiazole group, significant correlations were found between leptin levels at day 1 and clomethiazole dose (p = 0.004), clomethiazole and leptin at day 1/BMI (p = 0.009) and leptin at day 1 and clomethiazole/body surface (p = 0.006). Furthermore, patients with higher clomethiazole doses demonstrated significant higher leptin levels at day 1 (p = 0.044) and day 7 (p = 0.046). CONCLUSIONS: Our pilot data show a strong association between leptin levels and clomethiazole doses, thus supporting further research. PMID- 22042251 TI - How to connect an IgE-driven response with CTL activity? AB - One of the goals of cell-based immune therapy in cancer is the induction of tumor specific cytotoxic T-lymphocyte (CTL) responses. To achieve this objective, the ability of dendritic cells (DC) to cross-present tumor antigens can be exploited. One of the most efficient pathways for the induction of CTLs by cross presentation is mediated by immunoglobulins of the IgG class, which are used by DCs to sample antigen in the form of immune complexes via Fc-gamma receptors. Could DCs use an IgE-mediated cross-presentation mechanism in a comparable manner to induce CTLs? We here discuss the potential of two human IgE Fc receptors, FcepsilonRI and FcepsilonRII, to serve as antigen uptake receptors for IgE mediated cross-presentation. We conclude that the existence of an IgE-mediated cross-presentation pathway would provide a direct link between IgE-driven immune responses and CTL activity. PMID- 22042252 TI - Utility of PCA3 in patients undergoing repeat biopsy for prostate cancer. AB - BACKGROUND: Men with persistently elevated and/or rising PSA levels after negative prostate biopsy often undergo multiple repeat biopsies. Prostate cancer antigen 3 (PCA3) has emerged as a predictor of prostate cancer. METHODS: We sought to define the utility of PCA3 in combination with other clinical data in predicting the risk of prostate cancer on repeat biopsy. We retrospectively obtained PCA3, PSA, PSA density (PSAD), digital rectal examination (DRE) and transrectal ultrasound (TRUS) findings from 103 patients at a single institution who had at least one prior negative prostate biopsy. The sensitivity and specificity of PCA3 in detecting prostate cancer was determined. Receiver operating characteristics curves were produced for each variable individually and in multivariable analysis, controlling for PCA3, PSAD, TRUS, PSA and DRE. A nomogram was created, internally validated and compared to another recently published nomogram. RESULTS: Of the 103 patients, 37 (31%) had prostate cancer on repeat biopsy. The sensitivity and specificity of PCA3 (using a cut point of 25) was 0.67 and 0.64, respectively. In multivariable analyses, PCA3 was independently associated with prostate cancer (odds ratio: 1.02, 95% confidence interval: 1.01-1.04), with area under the curve (AUC) of 0.64. A multivariable model containing PCA3, PSAD, PSA, DRE and TRUS findings showed the most diagnostic accuracy (AUC: 0.82). CONCLUSIONS: In the setting of prior negative biopsies, PCA3 was independently associated with prostate cancer in a multivariable model. In combination with other clinical data, PCA3 is a valuable tool in assessing the risk of prostate cancer on repeat biopsy. PMID- 22042253 TI - Lanthanide-doped chitosan nanospheres as cell nuclei illuminator and fluorescent nonviral vector for plasmid DNA delivery. AB - Lanthanide-doped chitosan nanospheres (LDCNs) and lanthanide-Fe(3)O(4)-doped chitosan nanospheres (Fe(3)O(4)-LDCNs) are fabricated and show fluorescence, MRI effectiveness and desirable biocompatibility. Superior to most nanoparticles that were found retained in cytoplasmic organelles rather than the nucleus, the prepared chitosan nanospheres preferentially enter and illuminate the cell nuclei. Complexation of plasmid DNA (pDNA) to the nanospheres was accomplished via electrostatic forces between positively charged chitosan and negatively charged pDNA. Satisfactory results of the complexation indicate that the prepared chitosan nanospheres can serve as a potential fluorescent nonviral vector for pDNA delivery that can fulfill gene delivery and transfer efficiency assessment simultaneously, without an additional step of tagging fluorophores to the vectors carried out in fabrications of currently available pDNA delivery vectors. PMID- 22042254 TI - The maintenance gap: a new theoretical perspective on the evolution of aging. AB - One of the prevailing theories of aging, the disposable soma theory, views aging as the result of the accumulation of damage through imperfect maintenance. Aging, then, is explained from an evolutionary perspective by asserting that this lack of maintenance exists because the required resources are better invested in reproduction. However, the amount of maintenance necessary to prevent aging, 'maintenance requirement' has so far been largely neglected and has certainly not been considered from an evolutionary perspective. To our knowledge we are the first to do so, and arrive at the conclusion that all maintenance requirement needs an evolutionary explanation. Increases in maintenance requirement can only be selected for if these are linked with either higher fecundity or better capabilities to cope with environmental challenges to the integrity of the organism. Several observations are suggestive of the latter kind of trade-off, the existence of which leads to the inevitable conclusion that the level of maintenance requirement is in principle unbound. Even the allocation of all available resources to maintenance could be unable to stop aging in some organisms. This has major implications for our understanding of the aging process on both the evolutionary and the mechanistic level. It means that the expected effect of measures to reallocate resources to maintenance from reproduction may be small in some species. We need to have an idea of how much maintenance is necessary in the first place. Our explorations of how natural selection is expected to act on the maintenance requirement provides the first step in understanding this. PMID- 22042256 TI - A bis-bipyridine osmium(II) complex with an N,S-chelating 2-aminoethanesulfinate: photoinduced conversion of an amine to an imine donor group by air oxidation. AB - Treatment of [Os(bpy)(2)Cl(2)] (bpy = 2,2'-bipyridine) with 2-aminoethanethiolate was accompanied by air oxidation to give [Os(2-aminoethanesulfinato N,S)(bpy)(2)](+) ([1](+)), which was further oxidized by air to be converted into [Os(2-iminoethanesulfinato-N,S)(bpy)(2)](+) ([2](+)) under photoirradiation. Complex [2](+) was reverted back to [1](+) by treatment with BH(4)(-). PMID- 22042255 TI - The prevalence of triggers in paediatric migraine: a questionnaire study in 102 children and adolescents. AB - The prevalence and characterization of migraine triggers have not been rigorously studied in children and adolescents. Using a questionnaire, we retrospectively studied the prevalence of 15 predefined trigger factors in a clinic-based population. In 102 children and adolescents fulfilling the Second Edition of The International Headache Classification criteria for paediatric migraine, at least one migraine trigger was reported by the patient and/or was the parents' interpretation in 100% of patients. The mean number of migraine triggers reported per subject was 7. Mean time elapsed between exposure to a trigger factor and attack onset was comprised between 0 and 3 h in 88 patients (86%). The most common individual trigger was stress (75.5% of patients), followed by lack of sleep (69.6%), warm climate (68.6%) and video games (64.7%). Stress was also the most frequently reported migraine trigger always associated with attacks (24.5%). In conclusion, trigger factors were frequently reported by children and adolescents with migraine and stress was the most frequent. PMID- 22042257 TI - Lymphomatoid papulosis followed by pityriasis lichenoides: a common pathogenesis? AB - Pityriasis lichenoides (PL) and lymphomatoid papulosis (LyP) are uncommon idiopathic eruptions with overlapping clinical and histological features. Although current opinion indicates that PL and LyP are distinct and separate entities, molecular genetic evidence of T-cell clonality in both conditions suggests that an etiopathogenic relationship may exist. We report a patient who was diagnosed with LyP type B in 1985 followed by PL after 11 years. We hypothesize that LyP followed by PL in the same patient reflects differences in the host immune response to a common antigenic stimulus. PMID- 22042258 TI - Intravascular schwannoma. AB - Schwannoma is defined as a benign nerve sheath neoplasm of Schwann cell origin. Cutaneous schwannoma typically manifests along the course of peripheral nerves as a solitary, well-defined, skin-colored nodule within the deep dermis or subcutis of the flexor aspects of the extremities. Schwannoma enlarges slowly and typically follows a benign course, with local recurrence and malignant transformation being exceedingly rare. Although involvement of the vasculature by neurofibroma has been rarely reported, intravascular schwannoma has not been documented to date. We present a unique case of cutaneous schwannoma, as confirmed by histological morphology and immunohistochemistry, within the dermal venous system. Presentation of this case is followed by a discussion of the differential diagnoses of schwannoma, the possible etiologies of the extension of this lesion into the vasculature, and the significance of such a phenomenon. PMID- 22042259 TI - The differential diagnosis between primary cutaneous large B-cell lymphoma and cutaneous follicular lymphoma: prognostic and therapeutic implications. AB - The differential diagnosis between primary cutaneous diffuse large B-cell lymphoma and cutaneous follicular lymphoma is one of the most difficult aspects of dermatopathology, even though morphological criteria are well established and a wide panel of antibodies is available to every laboratory. Such diagnosis is, however, not trivial because it has important prognostic and therapeutic implications. Nevertheless, when the literature is reviewed, there is a feeling that the diagnostic deficits from the past could perhaps be responsible for the differences observed in the therapeutic results with less aggressive treatments, such as rituximab. The current report briefly revises some cases of primary cutaneous diffuse large B-cell lymphoma treated with rituximab, which have been reported in the literature. It also presents an additional case emphasizing the current approach to the differential diagnosis. PMID- 22042260 TI - Calcified bodies in New World cutaneous leishmaniasis. AB - We report a case of a 9-year-old boy who presented with 2 lesions that were compatible clinically with cutaneous leishmaniasis of the New World. A skin biopsy showed tuberculoid granulomas with rounded calcified bodies. The diagnosis was supported by a positive leishmanin test and a positive polymerase chain reaction. The patient responded to specific treatment for leishmaniasis. These calcified bodies, described under different names in the literature (Michaelis Gutmann bodies, Schaumann bodies, psammoma bodies, or conchoidal bodies), have been reported in an experimental leishmaniasis and, only once before, in a case of human leishmaniasis of the Old World. PMID- 22042261 TI - Nonnecrobiotic necrobiotic xanthogranuloma as an initial manifestation of paraproteinemia and small lymphocytic lymphoma in a patient with Sjogren syndrome. AB - We report a unique case of periocular nonnecrobiotic necrobiotic xanthogranuloma in a 52-year-old white woman with Sjogren syndrome who was subsequently found to have an immunoglobulin G paraproteinemia and coexisting small lymphocytic lymphoma. Therapy with fludarabine, cytoxan, and rituximab (FCR) resulted in a dramatic resolution of her sicca symptoms and periocular xanthogranulomas. This case further illustrates the association of hematolymphoid disorders with cutaneous xanthogranulomatous disease and the importance of additional appropriate laboratory and radiologic investigation for the accurate diagnosis of an underlying malignancy. PMID- 22042262 TI - Cutaneous granulomatous reaction after herpes zoster in drug-induced hypersensitivity syndrome. PMID- 22042263 TI - Ossifying trichilemmal cyst. AB - Although a trichilemmal cyst is a relatively common benign cutaneous condition and ossification has been observed within many cutaneous lesions to our knowledge, the association between ossification and trichilemmal cyst has not been previously reported. We describe for the first time the case of a trichilemmal cyst with marked osseous metaplasia arising on the scalp of a 46 year-old woman. Microscopically the lesion showed the typical features of a trichilemmal cyst with the finding of intra-extraluminal foci of calcification and the exceptional feature of mature bone formation. No areas of mature cartilage were observed near the focus of ossification. The cutaneous bone may have been directly formed from osteogenic stromal elements without a cartilaginous precursor (membranous or mesenchymal ossification). The dystrophic calcification might also contribute to the bone-forming process. PMID- 22042264 TI - A "high-risk" epithelioid hemangioendothelioma presenting as a solitary, ulcerated, subcutaneous tumor. AB - So-called "high-risk" epithelioid hemangioendotheliomas are uncommon neoplasms that demonstrate classic histopathologic features of epithelioid hemangioendotheliomas and a size larger than 3 cm or >3 mitotic figures per 50 high power fields. These neoplasms show an increased rate of metastasis (25% of cases) and are associated with a poor 5-year survival (59%). They may pose a diagnostic challenge for dermatopathologists as they mimic metastatic carcinoma, malignant mixed tumor, melanocytic neoplasms, epithelioid sarcoma, and epithelioid angiosarcoma. High-risk epithelioid hemangioendothelioma has not been previously reported as a solitary ulcerated mass in the skin. Here, we describe one such lesion that developed as a rapidly growing ulcerative skin tumor in a 33 year-old African American man with a remote history of Burkitt lymphoma. We also review the evolution and controversies in the understanding and classification of this neoplasm. PMID- 22042267 TI - Diversity of 16S rRNA genes from bacteria of sugarcane rhizosphere soil. AB - Sugarcane is an important agricultural product of Brazil, with a total production of more than 500 million tons. Knowledge of the bacterial community associated with agricultural crops and the soil status is a decisive step towards understanding how microorganisms influence crop productivity. However, most studies aim to isolate endophytic or rhizosphere bacteria associated with the plant by culture-dependent approaches. Culture-independent approaches allow a more comprehensive view of entire bacterial communities in the environment. In the present study, we have used this approach to assess the bacterial community in the rhizosphere soil of sugarcane at different times and under different nitrogen fertilization conditions. At the high taxonomic level, few differences between samples were observed, with the phylum Proteobacteria (29.6%) predominating, followed by Acidobacteria (23.4%), Bacteroidetes (12.1%), Firmicutes (10.2%), and Actinobacteria (5.6%). The exception was the Verrucomicrobia phylum whose prevalence in N-fertilized soils was approximately 0.7% and increased to 5.2% in the non-fertilized soil, suggesting that this group may be an indicator of nitrogen availability in soils. However, at low taxonomic levels a higher diversity was found associated with plants receiving nitrogen fertilizer. Bacillus was the most predominant genus, accounting for 19.7% of all genera observed. Classically reported nitrogen-fixing and/or plant growth promoting bacterial genera, such as Azospirillum, Rhizobium, Mesorhizobium, Bradyrhizobium, and Burkholderia were also found although at a lower prevalence. PMID- 22042266 TI - Do interactions between gut ecology and environmental chemicals contribute to obesity and diabetes? AB - BACKGROUND: Gut microbiota are important factors in obesity and diabetes, yet little is known about their role in the toxicodynamics of environmental chemicals, including those recently found to be obesogenic and diabetogenic. OBJECTIVES: We integrated evidence that independently links gut ecology and environmental chemicals to obesity and diabetes, providing a framework for suggesting how these environmental factors may interact with these diseases, and identified future research needs. METHODS: We examined studies with germ-free or antibiotic-treated laboratory animals, and human studies that evaluated how dietary influences and microbial changes affected obesity and diabetes. Strengths and weaknesses of studies evaluating how environmental chemical exposures may affect obesity and diabetes were summarized, and research gaps on how gut ecology may affect the disposition of environmental chemicals were identified. RESULTS: Mounting evidence indicates that gut microbiota composition affects obesity and diabetes, as does exposure to environmental chemicals. The toxicology and pharmacology literature also suggests that interindividual variations in gut microbiota may affect chemical metabolism via direct activation of chemicals, depletion of metabolites needed for biotransformation, alteration of host biotransformation enzyme activities, changes in enterohepatic circulation, altered bioavailability of environmental chemicals and/or antioxidants from food, and alterations in gut motility and barrier function. CONCLUSIONS: Variations in gut microbiota are likely to affect human toxicodynamics and increase individual exposure to obesogenic and diabetogenic chemicals. Combating the global obesity and diabetes epidemics requires a multifaceted approach that should include greater emphasis on understanding and controlling the impact of interindividual gut microbe variability on the disposition of environmental chemicals in humans. PMID- 22042268 TI - The effect of microgravity on tissue structure and function of rat testis. AB - To explore whether an environment of weightlessness will cause damage to the reproductive system of animals, we used the tail-suspension model to simulate microgravity, and investigated the effect of microgravity on the tissue structure and function of the testis in sexually mature male rats. Forty-eight male Wistar rats weighing 200-250 g were randomly assigned to three groups (N = 16 each): control, tail traction, and tail suspension. After the rats were suspended for 7 or 14 days, morphological changes of testis were evaluated by histological and electron microscopic methods. The expression of HSP70, bax/bcl-2 and AR (androgen receptor) in testis was measured by immunohistochemistry. Obvious pathological lesions were present in the testis after the rats were suspended for 7 or 14 days. We detected overexpression of HSP70 and an increase of apoptotic cells, which may have contributed to the injury to the testis. The expression of AR, as an effector molecule in the testis, was significantly decreased in the suspended groups compared to control (P < 0.01). We also observed that, with a longer time of suspension, the aforementioned pathological damage became more serious and some pathological injury to the testis was irreversible. The results demonstrated that a short- or medium-term microgravity environment could lead to severe irreversible damage to the structure of rat testis. PMID- 22042269 TI - New frontiers of primary antibody deficiencies. AB - Primary antibody deficiencies (PAD) form the largest group of inherited disorders of the immune system. They are characterized by a marked reduction or absence of serum immunoglobulins (Ig) due to disturbed B cell differentiation and by a poor response to vaccination. PAD can be divided into agammaglobulinemia, Ig class switch recombination deficiencies, and idiopathic hypogammaglobulinemia. Over the past 20 years, defects have been identified in 18 different genes, but in many PAD patients the underlying gene defects have not been found. Diagnosis of known PAD and discovery of new PAD is important for good patient care. In this review, we present the effects of genetic defects in the context of normal B cell differentiation, and we discuss how new technical developments can support understanding and discovering new genetic defects in PAD. PMID- 22042270 TI - Nanobiochips. AB - The actual progress towards biological chip devices consisting of nanostructured functional entities is summarized. The practical aspects of molecular nanobiochips are discussed, including the main surface chemistry platforms, as well as conventional and unconventional fabrication tools. Several successful biological demonstrations of the first generation of nanobiochip devices (mainly, different nanoarrays) are highlighted with the aim of revealing the potential of this technology in life sciences, medicine, and related areas. PMID- 22042271 TI - CD95-mediated cell signaling in cancer: mutations and post-translational modulations. AB - Apoptosis has emerged as a fundamental process important in tissue homeostasis, immune response, and during development. CD95 (also known as Fas), a member of the tumor necrosis factor receptor (TNF-R) superfamily, has been initially cloned as a death receptor. Its cognate ligand, CD95L, is mainly found at the plasma membrane of activated T-lymphocytes and natural killer cells where it contributes to the elimination of transformed and infected cells. According to its implication in the immune homeostasis and immune surveillance, and since several malignant cells of various histological origins exhibit loss-of-function mutations, which cause resistance towards the CD95-mediated apoptotic signal, CD95 has been classified as a tumor suppressor gene. Nevertheless, this assumption has been recently challenged, as in certain pathophysiological contexts, CD95 engagement transmits non-apoptotic signals that promote inflammation, carcinogenesis or liver/peripheral nerve regeneration. The focus of this review is to discuss these apparent contradictions of the known function(s) of CD95. PMID- 22042272 TI - Ten experiments that would make a difference in understanding immune mechanisms. AB - Jacques Monod used to say, "Never trust an experiment that is not supported by a good theory." Theory or conceptualization permits us to put order or structure into a vast amount of data in a way that increases understanding. Validly competing theories are most useful when they make testably disprovable predictions. Illustrating the theory-experiment interaction is the goal of this exercise. Stated bleakly, the answers derived from the theory-based experiments described here would impact dramatically on how we understand immune behavior. PMID- 22042273 TI - Asparaginases: a successful class of drugs against leukemias and lymphomas. PMID- 22042274 TI - Analysis of significant decrease in platelet count and thrombocytopenia, graded according to NCI-CTC, as prognostic risk markers for mortality and morbidity. AB - BACKGROUND: In adult intensive care unit, both thrombocytopenia (TP) and >=30% decrease in platelet count are associated with increased mortality, morbidity, and length of stay (LOS). The above mentioned observations have not been well reported in pediatric population. National Cancer Institute (NCI) common terminology criteria (CTC) is mainly used to report the adverse effects of cancer therapy, but not for grading TP. METHOD: Retrospective review of medical records was done for 204 patients. TP was graded according to the NCI-CTC. Each grade of TP and significant decrease (>=30%) in platelet count were studied for their association with LOS, mortality, and morbidity such as hospital-acquired pneumonia and positive blood culture. Four study groups were formed according to presence and/or absence of TP and significant decrease in platelet count. These groups were also studied for their association with mortality and LOS. RESULTS: Both >=30% decrease in platelets and TP (58.3% and 25% of patients, respectively) were associated with higher mortality and longer LOS (P<0.0001). Both have association also with infection. There was a trend of increased mortality with higher TP grade. Grade 4 TP was significantly associated with increased LOS (P=0.0001). When compared with neither group, groups with positive significant decrease were associated with higher mortality and LOS, even in the absence of TP. CONCLUSIONS: We can use the NCI-CTC for classification of TP, which would enable the standardization of TP grading system. A >=30% decrease in platelet count, even without TP, is a prognostic risk marker for mortality, morbidity, and LOS. PMID- 22042275 TI - Thalassemia-like phenotype in a novel complex hemoglobinopathy with alpha, beta, delta globin chain abnormalities. AB - The occurrence of multiple abnormalities of alpha, beta, delta, and gamma globin genes may lead to unusual and complex phenotypes when they arise simultaneously in the same individual. Here, we report the findings of an African American boy who coinherited 3 heterozygous globin gene abnormalities: the unstable beta globin chain variant; hemoglobin (Hb) Showa-Yakushiji [beta110(G12) Leu->Pro], the delta-globin chain variant; HbB2 [delta16(A13) Gly->Arg] and alpha thalassemia (alpha-thal); (alpha-/alphaalpha). Hb Showa-Yakushiji had been previously described in Japanese, Indian, and European populations. We report its first occurrence in a child of African ancestry who presented with anemia not responsive to iron and an incomplete beta-thalassemia minor phenotype. Although the clinical and laboratory features of Hb Showa-Yakushiji mimic those of a beta thalassemia, the coinheritance of the delta-globin chain variant Hb B2 suppressed the relative increase in Hb A2 usually observed in heterozygotes for the Hb Showa Yakushiji mutation. Protein-based methods detected only a trace amount of HbB2 and failed to reveal presence of Hb Showa-Yakushiji and alpha-thal. The latter were only identified through DNA analyses. The diagnostic difficulties, molecular characteristics, and genotype/phenotype correlations of this novel complex hemoglobinopathy syndrome are reviewed. PMID- 22042276 TI - Reirradiation and concomitant metronomic temozolomide: an efficient combination for local control in medulloblastoma disease? AB - Medulloblastoma (MB) is the most common malignant pediatric brain tumor and a rare adulthood tumor. Twenty percent to 30% of patients relapses and displays a poor prognosis. The management of recurrent disease represents a medical challenge as salvage therapy with high-dose chemotherapy is disappointing. We report a pilot study of reirradiation and concomitant metronomic temozolomide of MB focal recurrence. Five patients from 10 to 27 years old at time of first diagnosis were treated initially with upfront radiation therapy at full dose. They relapsed focally and progressed under chemotherapy with a time recurrence ranged from 2 to 15 years after initial diagnosis. Patients were then treated with 3-dimensional conformal reirradiation focused on the relapsed disease with a median dose of 28 Gy (1.8 Gy per fraction) and concomitant temozolomide (75 mg/m/d) alone or as part of a multidrug metronomic regimen. Five complete responses were obtained at the end of metronomic radiochemotherapy. The median follow-up was 28 months. At last follow-up, 3 patients progressed outside radiation field under maintenance chemotherapy, and 1 is free of disease. Only 1 patient relapsed in the reirradiation field. No neurological toxicity was observed. These results indicate a possible radiosensitizing effect of concomitant metronomic temozolomide with radiation therapy. This association could play a role in the management of high-risk MB patient with oligometastasis disease to increase local control. PMID- 22042277 TI - Polyethylene Glycol-conjugated L-asparaginase versus native L-asparaginase in combination with standard agents for children with acute lymphoblastic leukemia in second bone marrow relapse: a Children's Oncology Group Study (POG 8866). AB - BACKGROUND: Administration of L-asparaginase is limited by hypersensitivity reactions mediated by anti-asparaginase antibodies. To overcome this problem, native Escherichia coli L-asparaginase was conjugated to polyethylene glycol (PEG) to formulate PEG-L-asparaginase, a preparation with decreased immunogenicity and increased circulating half-life. In early trials, PEG-L asparaginase was tolerated by patients known to be hypersensitive to the native E. coli product. METHODS: The Pediatric Oncology Group conducted a phase II, randomized trial to compare the efficacy and toxicity of PEG-L-asparaginase compared with native E. coli asparaginase in children with acute lymphoblastic leukemia in second bone marrow relapse. All patients (n=76) received standard doses of vincristine and prednisone. Nonhypersensitive patients (n=34) were randomized to receive either PEG-L-asparaginase of 2500 IU/m/dose intramuscularly on days 1 and 15 (treatment I) or native E. coli asparaginase of 10,000 IU/m/dose intramuscularly on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (treatment II). Patients with a clinical history of an allergic reaction to unmodified asparaginase were directly assigned to treatment with PEG-L-asparaginase (n=42). Asparaginase levels and anti-asparaginase antibody titers were monitored in all patients. Response and toxicity were scored using conventional criteria. RESULTS: The complete response rate for the total study population was 41%. There was no difference in complete response between patients randomized to PEG (47%) and native asparaginase (41%). PEG was well tolerated even in patients with prior allergic reactions to native asparaginase. PEG half-life was shorter in patients with prior allergy. CONCLUSIONS: PEG asparaginase is a useful agent in patients with allergic reactions to native asparaginase. PMID- 22042278 TI - In silico engineering of L-asparaginase to have reduced glutaminase side activity for effective treatment of acute lymphoblastic leukemia. AB - L-Asparaginase, an enzyme drug used for the treatment of acute lymphoblastic leukemia and its effective usage in clinical arena is complicated owing to the significant Glutaminase side activity. To develop variants of the enzyme with reduced Glutaminase activity, in silico mutagenesis was done by replacing amino acids in the vicinity of the ligand binding site. It was identified that replacement of enzyme's active site amino acid Asp96 with Alanine decreased the Glutaminase activity by 30% and also increased the Asparaginase activity by 40%. Docking studies were carried out by Autodock 4.0 and binding energy for native enzyme when docked with glutamine was found to be -8.08 Kcal/mole, whereas for mutated protein it was found to be -5.97 Kcal/mole. It was also observed that replacement of active site with amino acids other than alanine did not show considerable change in both Asparaginase and Glutaminase activities. The designed enzyme model with reduced Glutaminase side activity may help to develop a variant of enzyme drug through protein engineering by site-directed mutagenesis and thus to produce a drug with reduced side effect for treating acute lymphoblastic leukemia in children. PMID- 22042279 TI - Acquired von Willebrand disease in an osteosarcoma patient. AB - Acquired von Willebrand disease is likely underdiagnosed due to the clinical variability in presentation and variety of conditions, including lymphoproliferative and myeloproliferative syndromes, autoimmunity, solid tumors, hypothyroidism, and cardiovascular disease, in which it can present. Pediatric patients with Wilms tumor have been reported in the literature with acquired von Willebrand disease and it has been theorized to occur in other pediatric solid tumors. Here we present the first reported case of acquired von Willebrand disease secondary to osteosarcoma in an adolescent patient, resolving spontaneously with treatment of her underlying disease. PMID- 22042280 TI - Co-occurrence of Chiari malformations and sickle cell disease-a diagnostic dilemma: a report of 4 cases and review of literature. AB - The co-occurrence of sickle cell disease (SCD) and Chiari malformation (CM) poses clinical and diagnostic challenge since symptoms of both conditions may overlap. Although SCD and CM do not have a causal relationship, the overlapping neurologic symptoms may pose a diagnostic dilemma. To the best of our knowledge, the clinical manifestations and long-term consequence of CM in children with SCD has hitherto not been reported in the literature. We describe clinical manifestations of co-occurrence of SCD and CM in a case series of 4 African American children. PMID- 22042281 TI - A patient with familial bone marrow failure and an inversion of chromosome 8. AB - Familial bone marrow failure has been associated with a variety of chromosomal aberrations. Chromosome 8 abnormalities have been described in association with neoplastic and hematologic disorders; however, to our knowledge, inversion of the long arm of chromosome 8 has not been described in the context of familial bone marrow failure. We describe a 9-year-old female with familial bone marrow failure and an inversion of chromosome 8 [inv (8) (q22, q24.3)]. Given the importance of considering the genetic determinants of familial bone marrow failure, the potential role of chromosome 8 abnormalities in the development of marrow failure is discussed. PMID- 22042282 TI - Cutaneous Ewing sarcoma: report of 2 cases and literature review of presentation, treatment, and outcome of 76 other reported cases. AB - Cutaneous Ewing sarcoma is a rare variant that has been poorly characterized and has no standard therapy. We report 2 patients with cutaneous Ewing sarcoma and review 76 other cases reported in the literature for demographics, presentation, treatment, and outcome. Only 2 patients presented with metastatic disease, and only 8 patients developed metastatic disease. Ninety-one percent of all patients are alive despite wide variations in treatment regimens. On the basis of this summary, treatment consisting of local control with surgery and/or radiation and abbreviated chemotherapy is proposed as a treatment option for this less aggressive Ewing sarcoma. PMID- 22042283 TI - Oral voriconazole versus intravenous low dose amphotericin B for primary antifungal prophylaxis in pediatric acute leukemia induction: a prospective, randomized, clinical study. AB - PURPOSE: Invasive fungal infections (IFI) are a major cause of infection-related mortality during induction chemotherapy of acute leukemia (AL) patients. Data on antifungal prophylaxis (AFP) in children are limited by retrospective design, small sample size, and variability of chemotherapy phases having different risk of IFI. There are no data comparing voriconazole versus amphotericin B (AmB) as AFP in either adult/pediatric AL. The objectives of this study were to compare efficacy and toxicity of AmB and voriconazole as AFP in pediatric AL patients. PATIENTS AND METHODS: As a pilot study, total 100 children (<=15 y) with denovo acute myeloid leukemia and acute lymphoblastic leukemia were randomized to either oral voriconazole or low dose intravenous AmB as AFP during induction chemotherapy. RESULTS: Failure of prophylaxis occurred in 14/50 patients in voriconazole arm (1 proven mucormycosis, 1 possible IFI, 11 empirical antifungal therapy, and 1 withdrawal owing to hepatotoxicity) and 17/50 patients in AmB arm (3 possible IFI, 13 empirical antifungal therapy, and 1 withdrawal owing to difficult venous access) (P=0.66). Of the 29 patients who had failure of prophylaxis unrelated to drug toxicity, computed tomography of the chest showed infiltrates in 10 patients with 3/12 in voriconazole arm and 7/16 in AmB arm (P=0.43). Drug-related serious adverse events were 6% versus 30% in voriconazole and AmB arms, respectively (P<0.01). Further, total number of toxicities per patient in AmB arm were significantly higher as compared with voriconazole arm (P<0.0001). CONCLUSION: This is the first randomized study comparing voriconazole with AmB in pediatric AL patients as AFP during induction chemotherapy; our results showed that oral voriconazole seems to be comparable with AmB with less toxicity and more convenience. (ClinicalTrials.gov identifier: NCT00624143). PMID- 22042284 TI - A novel splice site mutation in ANTXR2 (CMG2) gene results in systemic hyalinosis. AB - Systemic hyalinosis is a rare autosomal recessive inheritance disease characterized by accumulation of amorphous, unidentified hyaline material in skin and other organs, which leads to papulonodular skin lesions, gingival hypertrophy, flexion contractures of the joints, and large subcutaneous tumors. It is composed of 2 allelic syndromes, infantile systemic hyalinosis and juvenile hyaline fibromatosis. Here we describe a patient with juvenile hyaline fibromatosis confirmed by clinical and histopathologic findings, and genetic analysis, which revealed a novel homozygous splice site mutation IVS14+1G->T on exon 14 in anthrax toxin receptor 2 gene. PMID- 22042285 TI - In Utero diagnosis and management of a fetus with homozygous alpha-Thalassemia in the second trimester: a case report and literature review. AB - Alpha thalassemia with the absence of 4 alpha-globin genes leads to fetal hydrops and fetal death from anemia. Historically considered a lethal condition, optimal in utero management of homozygous alpha-thalassemia is unclear. A fetus of Filipino descent at 26 weeks gestation presented with ultrasound evidence of anemia. Cordocentesis confirmed anemia and homozygous alpha-thalassemia (--/--). Intrauterine transfusion corrected anemia but fetal growth restriction and oligohydramnios persisted. Intrauterine exchange transfusion improved hemoglobin parameters, fetal growth, and oligohydramnios. The late preterm infant was delivered with classic limb reduction defects. Hemoglobin Bart's is nonfunctional for oxygen transport, and intrauterine exchange transfusion may be effective first-line therapy and further investigation is warranted. PMID- 22042286 TI - Microquantity for macroquality: case study on the effect of selenium on chronic neutropenia. AB - Chronic neutropenia is a myeloid hematologic disorder with a broad spectrum of etiological factors. Selenium trace element deficiency was recently identified as one. We tested the impact of selenium replacement therapy in a patient with chronic neutropenia. All known etiological factors of neutropenia were ruled out and only selenium deficiency was retained. After administration of selenium in the form of seleno-yeast supplement 50 ug daily for 2 month, notable increase in white blood cell (WBC) count and absolute neutrophil count (ANC) was recorded. The supplementation was discontinued for 2 month and monitoring of WBC and ANC revealed gradual decrease of both WBC count and neutrophils. The latter absolute count returned to the prior baseline before selenium supplementation. This suggested that selenium had a clear effect on correcting the low level of WBC specifically neutrophils back to normal level thus reducing the condition of neutropenia in this particular patient. PMID- 22042287 TI - Primary hepatic Burkitt lymphoma in a child and review of literature. AB - Primary hepatic non-Hodgkin lymphoma is extremely rare in childhood and can be overlooked in differential diagnosis of liver masses. In this study, we describe an unusual case of primary hepatic Burkitt lymphoma in childhood. PMID- 22042288 TI - Myelomastocytic Leukemia With t(8;21) in a 3-year-old Child. AB - Here we report a 3-year-old boy with myelomastocytic leukemia. The patient presented with fatigue and right eye proptosis. Bone marrow revealed acute myeloid leukemia with t(8;21) and trisomy 8. Induction therapy produced marked reduction in marrow myeloblasts with the emergence of 13% atypical mast cells. These cells were subsequently identified in retrospect in the diagnostic marrow consistent with myelomastocytic leukemia. His clinical course was notable for the difficulty in the eradication of the leukemic process and resembled that of adults with systemic mastocytosis with associated hematologic non-mast cell lineage disease. To the best of our knowledge, this is the youngest individual reported. The implications of mast cell lineage involvement in acute myeloid leukemia are reviewed. PMID- 22042290 TI - The Trier Social Stress Test protocol for inducing psychological stress. AB - This article demonstrates a psychological stress protocol for use in a laboratory setting. Protocols that allow researchers to study the biological pathways of the stress response in health and disease are fundamental to the progress of research in stress and anxiety. Although numerous protocols exist for inducing stress response in the laboratory, many neglect to provide a naturalistic context or to incorporate aspects of social and psychological stress. Of psychological stress protocols, meta-analysis suggests that the Trier Social Stress Test (TSST) is the most useful and appropriate standardized protocol for studies of stress hormone reactivity. In the original description of the TSST, researchers sought to design and evaluate a procedure capable of inducing a reliable stress response in the majority of healthy volunteers. These researchers found elevations in heart rate, blood pressure and several endocrine stress markers in response to the TSST (a psychological stressor) compared to a saline injection (a physical stressor). Although the TSST has been modified to meet the needs of various research groups, it generally consists of a waiting period upon arrival, anticipatory speech preparation, speech performance, and verbal arithmetic performance periods, followed by one or more recovery periods. The TSST requires participants to prepare and deliver a speech, and verbally respond to a challenging arithmetic problem in the presence of a socially evaluative audience. Social evaluation and uncontrollability have been identified as key components of stress induction by the TSST. In use for over a decade, the goal of the TSST is to systematically induce a stress response in order to measure differences in reactivity, anxiety and activation of the hypothalamic-pituitary-adrenal (HPA) or sympathetic-adrenal medullary (SAM) axis during the task. Researchers generally assess changes in self-reported anxiety, physiological measures (e.g. heart rate), and/or neuroendocrine indices (e.g. the stress hormone cortisol) in response to the TSST. Many investigators have adopted salivary sampling for stress markers such as cortisol and alpha-amylase (a marker of autonomic nervous system activation) as an alternative to blood sampling to reduce the confounding stress of blood collection techniques. In addition to changes experienced by an individual completing the TSST, researchers can compare changes between different treatment groups (e.g. clinical versus healthy control samples) or the effectiveness of stress-reducing interventions. PMID- 22042291 TI - Fluid dynamics simulation of aqueous humour in a posterior-chamber phakic intraocular lens with a central perforation. AB - BACKGROUND: A modified implantable collamer lens (ICL) with a central hole (diameter, 0.36 mm), a "Hole-ICL", was created to improve aqueous humour circulation. The aim of this study was to investigate the fluid dynamic characteristics of aqueous humour in a Hole-ICL using computational fluid dynamics. METHODS: Fluid dynamics simulation using an ICL was performed with thermal-hydraulic analysis software FloEFD V5 (Mentor Graphics Corp.). For the simulation, three-dimensional eye models based on a modified Liou-Brennan model eye with conventional ICL (Model ICM, STAAR SURGICAL) and a Hole-ICL were used. Both ICLs were -9.0 diopters (D) and 12.0 mm in length, with an optic of 5.5 mm. The vaulting was 0.50 mm. The quantity of aqueous humour produced by the ciliary body was set at 2.80 MUl/min. Flow distribution between the anterior surface of the crystalline lens and the posterior surface of the ICL was also calculated, and trajectory analysis was performed. RESULTS: The flow velocity 0.25 mm in front of the centre of the crystalline lens was 1.52 * 10(-1) mm/sec for the Hole ICL and 1.21 * 10(-5) mm/sec for the conventional ICL. Outward flow from the hole in the Hole-ICL was confirmed by trajectory analysis. CONCLUSION: These results suggest that Hole-ICLs improve the circulation of aqueous humour to the anterior surface of the crystalline lens. PMID- 22042292 TI - Effect of Escherichia coli-produced recombinant human bone morphogenetic protein 2 on the regeneration of canine segmental ulnar defects. AB - Because bone morphogenetic protein 2 gene transfected Escherichia coli (E-BMP-2) produce recombinant human BMP-2 (rhBMP-2) more efficiently than mammalian cells (Chinese hamster ovary [CHO]-BMP-2), they may be a more cost-effective source of rhBMP-2 for clinical use. However, use of E-BMP-2 for regenerating long bones in large animals has not been reported. In the current study, we evaluated the healing efficacy of E-BMP-2 in a canine model. We created 2.5-cm critical-size segmental ulnar defects in test animals, then implanted E-BMP-2 and 700 mg of artificial bone (beta-tricalcium phosphate; beta-TCP) into the wounds. We examined the differential effects of 5 E-BMP-2 treatments (0, 35, 140, 560, and 2240 MUg) across 5 experimental groups (control, BMP35, BMP140, BMP560, and BMP2240). Radiography and computed tomography were used to observe the regeneration process. The groups in which higher doses of E-BMP-2 were administered (BMP560 and BMP2240) displayed more pronounced bone regeneration; the regenerated tissues connected to the host bone, and the cross-sectional areas of the regenerated bone were larger than those of the originals. The groups in which lower doses of E-BMP-2 were administered (BMP35 and BMP140) experienced relatively less bone regeneration; furthermore, the regenerated tissues failed to connect to the host bone. In these groups, the cross-sectional areas of the regenerated bone were equal to or smaller than those of the originals. No regeneration was observed in the control group. These findings suggest that, like CHO-BMP-2, E-BMP-2 can be used for the regeneration of large defects in long bones and that its clinical use might decrease the cost of bone regeneration treatments. PMID- 22042293 TI - Regulation of auxin response by miR393-targeted transport inhibitor response protein 1 is involved in normal development in Arabidopsis. AB - miR393, which is encoded by MIR393a and MIR393b in Arabidopsis, post transcriptionally regulates mRNAs for the F-box auxin receptors TIR1 (Transport Inhibitor Response Protein 1), AFB1 (Auxin Signaling F-box Protein 1), AFB2 and AFB3. However, biological functions of the miR393-TIR1/AFBs module in auxin response and plant development is not fully understood. In the study herein, we demonstrate that miR393 accumulated in response to exogenous IAA treatment, and its induction was due to enhanced MIR393b transcription but not MIR393a. Overexpression of a miR393-resistant form of TIR1 (mTIR1) enhanced auxin sensitivity and led to pleiotropic effects on plant development including inhibition of primary root growth, overproduction of lateral roots, altered leave phenotype and delayed flowering. Furthermore, miR393 level was increased in 35S:mTIR1 plant, suggesting that TIR1 promoted the expression of miR393 by a feedback loop. The interaction between miR393 and its target indicates a fine adjustment to the roles of the miR393-TIR1 module, which is required for auxin responses in plant development. PMID- 22042294 TI - Laparoendoscopic single-site lateral pancreaticojejunostomy. AB - BACKGROUND: Chronic pancreatitis is mainly managed with drugs, but surgery is required in selected groups of patients. The Partington procedure is still the procedure of choice for patients with a dilated main pancreatic duct but without an inflammatory pancreatic head mass. The same equivalent can be achieved by laparoscopic approach. Laparoendoscopic single-site surgery gained tremendous attention in the past few years. Complex surgeries are being reported using this technique. We report in this paper the first laparoendoscopic single-site lateral pancreaticojejunostomy (LPJ) for chronic calcific pancreatitis with dilated pancreatic duct. PATIENT AND METHOD: The procedure was performed on a 32-year-old female diagnosed to have chronic calcific pancreatitis. A single vertical 2.5-cm umbilical incision and one 10-mm and two 5-mm ports were made. The procedure was completed in 220 min without any intraoperative complication. There were no postoperative complications, and the patient was discharged on day 5 when she started taking routine diet. CONCLUSION: This preliminary experience suggests that single-incision laparoscopic LPJ is feasible and safe when performed by an experienced laparoscopic surgeon. It has a cosmetic advantage over laparoscopic LPJ. However, it remains to be determined if this technique offers additional advantages of decreased analgesia, decreased hospital stay or cost effectiveness. Further studies are required to analyze these factors. PMID- 22042295 TI - DNA-catalyzed reactivity of a phosphoramidate functional group and formation of an unusual pyrophosphoramidate linkage. AB - During in vitro selection for DNA-catalyzed lysine reactivity, we identified a deoxyribozyme that instead catalyzes nucleophilic attack of a phosphoramidate functional group at a 5'-triphosphate-RNA, forming an unusual pyrophosphoramidate (N-P(V)-O-P(V)) linkage. This finding highlights the relatively poor nucleophilicity of nitrogen using nucleic acid catalysts, indicating a major challenge for future experimental investigation. PMID- 22042296 TI - Preparation of graphene/tetrathiafulvalene nanocomposite switchable surfaces. AB - A one step process for simultaneous reduction and functionalization of graphene oxide using tetrathiafulvalene (TTF) is described. Chemical oxidation of TTF to TTF(2+) using an aqueous solution of Fe(ClO(4))(3) expels the charged molecule from the graphene nanosheets, while subsequent immersion in neutral TTF solution allows the capture of the TTF molecules. PMID- 22042297 TI - The Rick Hansen Spinal Cord Injury Registry (RHSCIR): a national patient registry. AB - STUDY DESIGN: Development of a prospective patient registry. OBJECTIVE: To develop a patient registry for persons with traumatic spinal cord injuries (SCI), which can be used to answer research questions and improve patient outcomes. SETTING: Nine provinces in Canada. METHODS: The Rick Hansen Spinal Cord Injury Registry (RHSCIR) is part of the Translational Research Program of the Rick Hansen Institute. The launch of RHSCIR in 2004 heralded the initiation of the first nation-wide SCI patient registry within Canada. Currently, RHSCIR is being implemented in 14 cities located in 9 provinces, and there are over 1500 individuals who have sustained an acute traumatic SCI registered to date. Data are captured from the pre-hospital, acute and rehabilitation phases of care, and participants are followed in the community at 1, 2, 5 and then every 5 years post injury. RESULTS: During the development of RHSCIR, there were many challenges that were overcome in selecting data elements, establishing the governance structure, and creating a patient privacy and confidentiality framework across multiple provincial jurisdictions. The benefits of implementing a national registry are now being realized. The collection of an internationally standardized set of clinical information is helping inform clinicians of beneficial interventions and encouraging a shift towards evidence-based practices. Furthermore, through RHSCIR, a network is forming amongst SCI clinicians and researchers, which is fostering new collaborations and the launch of multi-center clinical trials. CONCLUSIONS: For networks that are establishing SCI registries, the experiences and lessons learned in the development of RHSCIR may provide useful insights and guidance. PMID- 22042298 TI - Associations between psychological factors and quality of life ratings in persons with spinal cord injury: a systematic review. AB - STUDY DESIGN: Systematic review. OBJECTIVES: To review the literature on relationships between psychological factors and quality of life (QOL) of persons with spinal cord injury (SCI). SETTING: NA. METHODS: A systematic literature search was conducted in several online databases (PubMed, Embase and PsychInfo). Articles were included if they provided quantitative information on associations between QOL-related dependent variables and psychological factors as independent variables in an SCI population. The search was limited to empirical studies published in English. The methodological quality of the included articles was assessed. RESULTS: A total of 48 studies were included. Total locus of control, sense of coherence, self-worth, hope, purpose in life and positive affect were consistently associated with greater QOL. Negative affect and posttraumatic cognitions were consistently associated with lower QOL. Inconsistent evidence was found for subscales of locus of control, the role of attribution of blame, spirituality, personality, appraisals, passive coping and emotion-focused coping. No evidence was found for an association between active problem-focused coping styles and QOL. CONCLUSION: Many psychological factors were strongly and consistently related to QOL, but for some others no or inconsistent evidence was found. Further research should (1) use larger study groups, preferably in longitudinal designs, (2) improve terminological precision and avoid conceptual overlap between determinants and outcomes, (3) increase uniformity of questionnaires and (4) reexamine concepts that have been abandoned prematurely, such as personality and social comparison. PMID- 22042299 TI - George Riddoch: the man who found Ludwig Guttmann. AB - STUDY DESIGN: This is a review article. OBJECTIVES: To evaluate the role played by George Riddoch in the setting up of spinal units in the UK and the appointment of Ludwig Guttmann. SETTING: Wendover, UK. METHODS: Review of the literature and the public records. RESULTS: Not applicable. CONCLUSIONS: George Riddoch's contribution to our understanding of the treatment for spinal injuries by means of his research on the patho-physiology, treatment and the setting up of spinal injury units in World Wars I and II was outstanding, especially his role in finding, appointing and supervising Ludwig Guttmann at the National Spinal Injuries Centre. PMID- 22042300 TI - Controversy over the pharmacological treatments of storage symptoms in spinal cord injury patients: a literature overview. AB - STUDY DESIGN: Our aim was to locate research and communicate the evidence found from scientific studies pertaining to the treatment of neurogenic detrusor overactivity (NDO) in the chronic stage of spinal cord injury (SCI). OBJECTIVE: To address the controversy over the traditional (antimuscarinics) and the 'new' treatments for NDO and try to offer an insight on the rationale underlying the development of new drugs such as botulinum toxin (BTX), vanilloids, nociceptin/orphanin FQ. As a final point, to provide information on a new class of cation channels, the Degenerin/Epithelial Na(+)Channel (Deg/ENaC) Family that could be future targets for the management of NDO. SETTING: International. METHODS: Overview of English literature on drug management of NDO. RESULTS: Agents that block the 'efferent' function of micturition reflex, such as antimuscarinics, are currently first-line therapy for NDO. They reach the highest level of evidence (1a) and grade of recommendation (A). However, many patients and physicians believe that the 'efferent' pharmacological management of NDO is not completely satisfactory. Consequently, research is trying to address issues of efficacy, tolerability and convenience of new therapeutic strategies targeting the 'afferent' function. CONCLUSION: Antimuscarinic therapy increases the bladder capacity and delays the initial urge to void. However, in some patients they fail to achieve the patient's therapeutic goals. New interesting approaches have been investigated in the last few years. BTX seems to be very promising in treating neurogenic overactive bladder (OAB), but other compounds are now on the horizon. PMID- 22042301 TI - Validation of the REMA score for predicting mast cell clonality and systemic mastocytosis in patients with systemic mast cell activation symptoms. AB - BACKGROUND: A variable percentage of patients with systemic mast cell (MC) activation symptoms meet criteria for systemic mastocytosis (SM). We prospectively evaluated the clinical utility of the REMA score versus serum baseline tryptase (sBt) levels for predicting MC clonality and SM in 158 patients with systemic MC activation symptoms in the absence of mastocytosis in the skin (MIS). METHODS: World Health Organization criteria for SM were applied in all cases. MC clonality was defined as the presence of KIT-mutated MC or by a clonal HUMARA test. The REMA score consisted of the assignment of positive or negative points as follows: male (+1), female (-1), sBt <15 MUg/l (-1) or >25 MUg/l (+2), presence (-2) or absence (+1) of pruritus, hives or angioedema and presence (+3) of presyncope or syncope. Efficiency of the REMA score for predicting MC clonality and SM was assessed by receiver operating characteristic (ROC) curve analyses and compared to those obtained by means of sBt levels alone. RESULTS: Molecular studies revealed the presence of clonal MC in 68/80 SM cases and in 11/78 patients who did not meet the criteria for SM. ROC curve analyses confirmed the greater sensitivity and a similar specificity of the REMA score versus sBt levels (84 vs. 59% and 74 vs. 70% for MC clonality and 87 vs. 62% and 73 vs. 71% for SM, respectively). CONCLUSIONS: Our results confirm the clinical utility of the REMA score to predict MC clonality and SM in patients suffering from systemic MC activation symptoms without MIS. PMID- 22042302 TI - Salt effect of nisin Z isolated from a marine fish on the growth inhibition of Streptococcus iniae, a pathogen of streptococcosis. AB - A bacteriocin-producing Lactococcus lactis subsp. lactis was isolated from the intestine of olive flounder. The bacteriocin was identified as nisin Z. It was active against Gram-positive bacteria. Nisin Z at 3,200 arbitrary units (AU) was more effective in seawater than in PBS; growth of Streptococcus iniae was completely inhibited within 3 h. Nisin Z preparations with 3.5% (w/v) NaCl was the most effective against S. iniae being similar to nisin Z in seawater. Nisin Z is thus a good alternative to antibiotics to prevent streptococcosis caused by S. iniae aquaculture systems. PMID- 22042303 TI - Enhancement of pH stability and activity of glycerol dehydratase from Klebsiella pneumoniae by rational design. AB - Glycerol dehydratase (GDHt) is a key and rate-limiting enzyme in the pathway of 1,3-propanediol (1,3-PD) synthesis. The improvement of GDHt's stability and enzymatic activity is desirable for the biosynthesis of 1,3-PD. The gldABC gene encoding GDHt of Klebsiella pneumoniae was cloned and expressed in Escherichia coli XL10-Gold, and the mutation sites of GDHt were obtained through prediction by PoPMuSiC program. Consequently, two mutants (KpG60 and KpG525) were developed by rational design through site-mutagenesis based on 3D structure which was constructed from homology modeling. Analyses of enzymatic properties showed that pH stability of the mutants was about 1.25-2 times higher than that of the wild type, and specific activity, V(max) and K(cat)/K(m) of KpG525 were about 1.5-2 times higher than those of the wild type. This work presented a simple and useful measure to improve the performance of industrial enzyme. PMID- 22042304 TI - Outcomes of anterior and posterior instrumentation under different surgical procedures for treating thoracic and lumbar spinal tuberculosis in adults. AB - PURPOSE: There are few articles in the literature comparing outcomes between anterior and posterior instrumentation in the management of thoracic and lumbar spinal tuberculosis (TB). METHODS: Between January 2004 and December 2009, 217 adult patients, average age 39 (range 16-67) years with thoracic and lumbar spinal TB were treated by anterior radical debridement and fusion plus instrumentation, anterior radical debridement with fusion and posterior fusion with instrumentation, posterolateral debridement and fusion plus posterior instrumentation or transpedicular debridement and posterior fusion with instrumentation in a single- or two-stage procedure. We followed up 165 patients for 22-72 (mean 37) months. Of these, 138 underwent more than three weeks chemotherapy with isoniazid, rifampin, pyrazinamide and ethambutol, and the remaining 27 underwent operation for neurological impairment within six to 18 hours of the same chemotherapy regimen. In no case did relapse occur. Apart from eight patients with skip lesions treated by hybrid anterior and posterior instrumentation, anterior instrumentation was used in 74 patients (group A) and 83 patients (group B) were fixed posteriorly. RESULTS: In both groups, local symptoms were relieved significantly one to three weeks postoperatively; ten of 14 patients (71%) in group A and 14 of 19 (74%) in group B with neurological deficit had excellent or good clinical results (P > 0.05). Erythrocyte sedimentation rates (ESR) returned from 43.6 mm/h and 42.7 mm/h, respectively, preoperatively to normal levels eight to 12 weeks postoperatively. Kyphosis degree was corrected by a mean of 11.5 degrees in group A and 12.6 degrees in group B, respectively (P < 0.01). Correction loss was 6.8 degrees in group A and 6.1 degrees in group B at the last follow-up (P < 0.01). Fusion rates of the grafting bone were 92.5% and 91.8%, respectively, at final follow-up (P > 0.05). Severe complications did not occur. CONCLUSION: These results suggest that both anterior and posterior instrumentation attain good results for correction of the deformity and maintaining correction, foci clearance, spinal-cord decompression and pain relief in the treatment of thoracic and lumbar spinal TB providing that the operative indication is accurately identified. However, the posterior approach may be superior to anterior instrumentation to correct deformity and maintain that correction. PMID- 22042305 TI - Video-rate scanning confocal microscopy and microendoscopy. AB - Confocal microscopy has become an invaluable tool in biology and the biomedical sciences, enabling rapid, high-sensitivity, and high-resolution optical sectioning of complex systems. Confocal microscopy is routinely used, for example, to study specific cellular targets, monitor dynamics in living cells, and visualize the three dimensional evolution of entire organisms. Extensions of confocal imaging systems, such as confocal microendoscopes, allow for high resolution imaging in vivo and are currently being applied to disease imaging and diagnosis in clinical settings. Confocal microscopy provides three-dimensional resolution by creating so-called "optical sections" using straightforward geometrical optics. In a standard wide-field microscope, fluorescence generated from a sample is collected by an objective lens and relayed directly to a detector. While acceptable for imaging thin samples, thick samples become blurred by fluorescence generated above and below the objective focal plane. In contrast, confocal microscopy enables virtual, optical sectioning of samples, rejecting out of-focus light to build high resolution three-dimensional representations of samples. Confocal microscopes achieve this feat by using a confocal aperture in the detection beam path. The fluorescence collected from a sample by the objective is relayed back through the scanning mirrors and through the primary dichroic mirror, a mirror carefully selected to reflect shorter wavelengths such as the laser excitation beam while passing the longer, Stokes-shifted fluorescence emission. This long-wavelength fluorescence signal is then passed to a pair of lenses on either side of a pinhole that is positioned at a plane exactly conjugate with the focal plane of the objective lens. Photons collected from the focal volume of the object are collimated by the objective lens and are focused by the confocal lenses through the pinhole. Fluorescence generated above or below the focal plane will therefore not be collimated properly, and will not pass through the confocal pinhole, creating an optical section in which only light from the microscope focus is visible. (Fig 1). Thus the pinhole effectively acts as a virtual aperture in the focal plane, confining the detected emission to only one limited spatial location. Modern commercial confocal microscopes offer users fully automated operation, making formerly complex imaging procedures relatively straightforward and accessible. Despite the flexibility and power of these systems, commercial confocal microscopes are not well suited for all confocal imaging tasks, such as many in vivo imaging applications. Without the ability to create customized imaging systems to meet their needs, important experiments can remain out of reach to many scientists. In this article, we provide a step-by-step method for the complete construction of a custom, video rate confocal imaging system from basic components. The upright microscope will be constructed using a resonant galvanometric mirror to provide the fast scanning axis, while a standard speed resonant galvanometric mirror will scan the slow axis. To create a precise scanned beam in the objective lens focus, these mirrors will be positioned at the so-called telecentric planes using four relay lenses. Confocal detection will be accomplished using a standard, off-the-shelf photomultiplier tube (PMT), and the images will be captured and displayed using a Matrox framegrabber card and the included software. PMID- 22042307 TI - The big picture: storytelling ability in adults with autism spectrum conditions. AB - Previous work on story-telling ability in autism spectrum conditions (ASC) has found a pattern of relatively intact use of story grammar in ASC narratives; however, prior analysis has concentrated primarily on whether specific story components are included, rather than how they are included. The present study analyzes an existing narrative dataset, concentrating on the kind of information that individuals with and without high functioning autism or Asperger syndrome include about story elements such as setting, character, conflict, and resolution. This analysis showed that individuals with ASC are biased toward providing local over global details about each element, regardless of whether the element involved mental content. These results are discussed in terms of the Weak Central Coherence and Hyper-Systemizing theories. PMID- 22042308 TI - Empathic responding in toddlers at risk for an autism spectrum disorder. AB - Empathy deficits represent an important social impairment in autism spectrum disorders (ASD), but little is known about the early development of empathy prior to diagnosis. This study examined empathic responding to parental distress in toddlers at risk for an ASD. Children later diagnosed with an ASD engaged in less empathic responding at 24 and 30 months than children with no later diagnosis. Lower empathic responding was associated with higher autism symptomatology at 30 months. This is the first study to examine empathy deficits in response to parental distress in toddlers prior to ASD diagnosis. Early empathic responding may represent a unique developing social skill that indexes the overall severity of later ASD symptomatology in at-risk children. PMID- 22042309 TI - Using individualized reinforcers and hierarchical exposure to increase food flexibility in children with autism spectrum disorders. AB - Inflexibility is a major characteristic of autism. In the present study we addressed inflexible mealtime behaviors and collected longitudinal data across 48 foods for 3 children, ages 6.4-7.8 years, diagnosed with autism spectrum disorder, for up to 22 weeks. Participants exhibited severe challenges with adherence to an extremely restricted repertoire of foods. We employed clinical replication and multiple baseline designs across participants to assess the effects of individualized reinforcement and hierarchical exposure to increase flexibility. Results showed that following intervention, all participants expanded their food repertoire and spontaneously requested new foods during follow up/generalization. Implications for clinical practice and directions for further research are discussed. PMID- 22042311 TI - Substance use disorders and comorbid mental disorders in first-time admitted patients from a catchment area. AB - AIM: To describe lifetime mental disorders in patients with substance use disorders (SUD) admitted for the first time to specialized treatment for psychiatric or addiction problems from a catchment area. METHODS: Special efforts were made to include all eligible patients and secure completion of thorough assessments, including the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) and the Structured Clinical Interview for DSM-IV axis II personality disorders (SCID-II). The strength of this study lies in its rigorous patient recruitment and assessment methods. RESULTS: Of 61 patients, 53 had alcohol use disorder (AUD). Of these, 28 had AUD only, and 25 had an additional drug use disorder (DUD). 89% had comorbid axis I (85%) or axis II (46%) disorders. The most prevalent axis I disorders were major depressive disorder (71%), social phobia (31%) and posttraumatic stress disorder (18%). Among those with comorbid psychiatric disorders (n = 54), 25 (41% of the sample) had disorders considered to be independent of their substance use only, 4 patients (7%) had substance-induced disorders only, and 23 patients (38%) had both independent and substance-induced disorders. CONCLUSION: Comorbid mental disorders were remarkably prevalent in these SUD patients who were admitted for the first time. PMID- 22042312 TI - Silver metallation of hen egg white lysozyme: X-ray crystal structure and NMR studies. AB - The X-ray crystal structure, NMR binding studies, and enzyme activity of silver(I) metallated hen egg white lysozyme are presented. Primary bonding of silver is observed through His15 with secondary bonding interactions coming from nearby Arg14 and Asp87. A covalently bound nitrate completes a four coordinate binding pocket. PMID- 22042313 TI - [Acromegalic cardiomyopathy]. AB - Acromegaly is an endocrine disease with specific somatic changes due to an excess of growth hormone. The majority of cases are caused by growth hormone producing pituitary tumors. Cardiovascular complications, which can be detected even in the early stages of the disease, are considered as major contributing factors in the increased morbidity and mortality of the patients. In this review authors briefly summarize clinical characteristics of acromegalic cardiomyopathy. PMID- 22042314 TI - [Affective temperaments: from neurobiological roots to clinical application]. AB - The Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) has grown to be a clinically important outcome measure in the diagnosis and the clinical course of mood disorders. However, temperaments, which represent the biologically stable core of personality, are not just antecedents of major affective disorders, but also serve as a reservoir of genetically advantageous traits for the survival of different cultures. The rapidly growing body of research in psychiatric and non-psychiatric fields even raises the question of temperament as a common root in psychiatric and somatic disorders, providing a new meaning for the construct of psychosomatic disorders. In this review we aim to summarize current knowledge on both the neurobiological background and clinical importance of affective temperaments including implications for future research. PMID- 22042315 TI - [Ultrasonography in the diagnosis of ovarian and endometrial carcinoma]. AB - Transvaginal sonography has become a crucial part of the routine gynecologic examination. It offers now a great help in the diagnosis of almost all gynecological diseases. Transvaginal ultrasound means the first step in the diagnosis of the first two most common gynecological malignancies, and in many cases we are able to set up a diagnosis of its own. The purpose of this article is to emphasize the significant role of transvaginal ultrasonography in the diagnosis of these two dieseases mentioned above, with summarizing the latest developments regarding the capabilities of sonography (Doppler-technique, three dimensional ultrasonograpy). PMID- 22042316 TI - [Translational medicine]. AB - Translational medicine is the emerging scientific discipline of the last decade which will set the benchmark for the pharmaceutical industry research and development, integrates inputs from the basic sciences of computer modeling and laboratory research through the pre-clinical and clinical phases of human research to the assimilation of new therapies and treatments into everyday practice of patient care and prevention. With this brief insight authors tried in their humble way to summarize the underlying basis, the present and the potential future of this emerging view, to draw attention to some of the challenges and tasks it faces and to highlight some of the promising approaches, trends and model developments and applications. PMID- 22042317 TI - ["Hannibal ante portas" -- technical development and health care reorganization]. AB - Authors intend to analyze the impact of medical technical development on the Hungarian health care system and try to draw attention to potentially necessary measures for professional and structural health care reorganization. PMID- 22042318 TI - [Tomato peel: rare cause of biliary tract obstruction]. AB - Foreign bodies in the biliary tree are rare causes of obstructive jaundice. Food bezoars are infrequent as well. They can cause biliary obstruction after biliary tract interventions, or in the presence of biliary-bowel fistula or duodenum diverticulum. Food bezoars usually pass the gastrointestinal tract without any symptoms, but they can cause abdominal pain and obstructive jaundice in the case of biliary tract obstruction. Endoscopic retrograde cholangio-pancreatography has the major role in the diagnosis and the treatment of the disease. Authors summarize the medical history of a 91-year-old female patient, who developed vomiting and right subcostal pain due to the presence of tomato peel within the ductus choledochus. PMID- 22042320 TI - Halichonines A, B, and C, novel sesquiterpene alkaloids from the marine sponge Halichondria okadai Kadota. AB - Novel sesquiterpene alkaloids, halichonines A (1), B (2), and C (3), were identified from the marine sponge Halichondria okadai Kadota. By spectroscopic analyses and synthesis, their structures were revealed to include a 6,6-bicyclic ring system and two prenylated amine moieties. In addition, 2 induced apoptosis in HL60 human leukemia cells. PMID- 22042321 TI - Is it time to reconsider the role of patient co-payments for pharmaceuticals in Europe? PMID- 22042322 TI - Epilepsy in Sweden: health care costs and loss of productivity--a register-based approach. AB - PURPOSE: The objective was to estimate health care costs and productivity losses due to epilepsy in Sweden and to compare these estimates to previously published estimates. METHODS: Register data on health care utilisation, pharmaceutical sales, permanent disability and mortality were used to calculate health care costs and costs that accrue due to productivity losses. By linkage of register information, we were able to distinguish pharmaceuticals prescribed against epilepsy from prescriptions that were prompted by other indications. RESULTS: The estimated total cost of epilepsy in Sweden in 2009 was 441 million, which corresponds to an annual per-patient cost of 8,275. Health care accounted for about 16% of the estimated total cost, and drug costs accounted for about 7% of the total cost. The estimated health care cost corresponded to about 0.2% of the total health care cost in Sweden in 2009. Indirect costs were estimated at 370 million, 84% of which was due to sickness absenteeism. Costs resulting from epilepsy-attributable premature deaths or permanent disability to work accounted for about 1% of the total indirect cost in Sweden in 2009. DISCUSSION: The per-patient cost of epilepsy is substantial. Thus, even though the prevalence of the illness is relatively small, the aggregated cost that epilepsy incurs on society is significant. PMID- 22042323 TI - Vascular resistance of central retinal and ophthalmic arteries in postmenopausal women after use of tibolone. AB - OBJECTIVE: The aim of this study was to evaluate the effect of tibolone on vascular resistance of the central retinal and ophthalmic artery in postmenopausal women and to compare this effect with that of placebo using transorbital ultrasound with Doppler velocimetry. METHODS: We performed a prospective randomized, double-blinded, placebo-controlled study. A total of 100 healthy postmenopausal women (follicle-stimulating hormone, >40 IU/L) younger than 65 years were studied. The participants were randomly allocated to two groups: placebo (n = 50) and tibolone (2.5 mg; n = 50). Transorbital Doppler velocimetric ultrasound was performed before treatment and 80 days after. RESULTS: The mean age was similar in both groups. Participants who received tibolone did not show any difference in pulsatility index, resistance index, and systole/diastole ratio of the central retinal and ophthalmic arteries after treatment. The same was observed in participants who received placebo. CONCLUSIONS: Our study demonstrates that tibolone administration to healthy postmenopausal women does not affect the resistance of small-caliber cerebral arteries. PMID- 22042324 TI - Development and validation of a simple model based on anthropometry: estimating fat mass for white postmenopausal women. AB - OBJECTIVE: The aim of this study was to develop and validate a simple anthropometric model that estimates the fat mass of white postmenopausal women and compare it to other models available in the literature. METHODS: Anthropometric data such as height, weight, waist and gluteal circumferences, biceps, triceps, suprailiac, and subscapular skinfolds, which were incorporated for the development and validation of this model, were derived from 276 white postmenopausal women. Dual-energy x-ray absorptiometry was used as the reference method. Furthermore, a comparison with other models was made using Bland-Altman analysis and intraclass correlation coefficient. RESULTS: The model developed in the current study was: fat mass = 0.069 * biceps + 0.553 * weight - 14.655 * height + 0.218 * gluteal circumference - 9.830 (r = 0.934, P < 0.001). The Bland Altman reliability analysis on the validation cohort showed a non-statistically significant bias of 0.158 kg and limits of agreement of +/-4.21 kg; the intraclass correlation coefficient was 0.983. Furthermore, the validity of the current model also remained significant in different levels of BMI, ranging from 20.5-42 kg/m. When other models available in the literature were tested in the current cohort, bias ranged from -1.239 to -6.996 kg, while the limits of agreement from +/-5.25 to +/-8.05 kg. CONCLUSIONS: The model developed in the current work was found to be valid for the assessment of postmenopausal women's fat mass at normal, overweight and obese BMI ranges, and can be easily applied in clinical practice and research. PMID- 22042325 TI - Neuroprotection of green tea catechins on surgical menopause-induced overactive bladder in a rat model. AB - OBJECTIVE: A rat model of ovariectomy-induced voiding dysfunction has been established, which mimicked the urge incontinence in postmenopausal women. Previous studies have identified strong anti-inflammatory/antioxidant properties of green tea and its associated polyphenols. The aim of this study was to evaluate whether the green tea extract, epigallocatechin gallate (EGCG), could prevent an ovariectomy-induced overactive bladder. METHODS: The study included 48 female Sprague-Dawley rats, which were divided into four groups. After bilateral ovariectomy during the following 6-month period, 12 rats received an intraperitoneal injection of saline, 24 rats received either a low-dose (1 MUM kg(-1) d(-1)) or a high-dose (10 MUM kg(-1) d(-1)) EGCG intraperitoneal injection. The sham group consisted of twelve rats that were not ovariectomized. In vivo isovolumetric cystometrograms were performed in all groups before the animals were euthanized. The immunofluorescence study used neurofilament stains to evaluate intramural nerve damage. Western immunoblots and real-time polymerase chain reaction were performed to determine M2 and M3 muscarinic cholinergic receptors (MChRs) at both protein and messenger RNA (mRNA) expressions. RESULTS: Long-term ovariectomy significantly increased non-voiding contractions, whereas treatment with EGCG significantly attenuated the frequency of non-voiding contractions. Ovariectomy significantly decreased the numbers of neurofilament and increased M2 and M3 MChR protein and mRNA expressions. Treatment with EGCG restored the amount of neurofilament staining and decreased M2 and M3 MChR protein and mRNA overexpressions. CONCLUSIONS: This study confirmed that ovary hormone deficiency induced overactive bladder dysfunction via intramural nerve damage and muscarinic receptor overexpression. EGCG prevented ovariectomy-induced bladder dysfunction through neuroprotective effects in a dose-dependent fashion. PMID- 22042326 TI - Symptom clusters at midlife: a four-country comparison of checklist and qualitative responses. AB - OBJECTIVE: The purpose of this study was to examine the frequency and clustering of somatic symptoms as reported by women aged 45 to 55 years in four countries, to compare women's responses to open-ended questions with those derived from structured checklists, and to assess the extent to which bodily symptoms grouped with emotional complaints. METHODS: The Decisions at Menopause Study recruited 1,193 women from the general population in Beirut, Lebanon; Rabat, Morocco; Madrid, Spain; and central Massachusetts. Women participated in semistructured interviews on health, menopause, and bodily changes at midlife. The women's responses to symptom checklists and their statements in response to open-ended questions were analyzed through factor and textual analyses. RESULTS: There was considerable consistency between the frequencies of quantitative and qualitative responses, and analyses of qualitative data illustrate the extent to which women associate somatic and emotional complaints. As shown in their responses to the open-ended questions, the women in Massachusetts and Spain did not often cluster somatic with emotional symptoms. In Morocco, dizziness, fatigue, and headaches were clustered with emotional symptoms. Women in Lebanon explicitly associated shortness of breath, chest pain, palpitations, dizziness, fatigue, gastrointestinal complaints, headaches, and, to a lesser extent, joint pain and numbness with emotional symptoms. CONCLUSIONS: The number of volunteered symptom responses was small because the respondents were relatively healthy; however, the extent and pattern of association between somatic and emotional symptoms varied across sites. Certain somatic symptoms may be more likely to communicate psychosocial distress in particular cultures. These results have implications for patterns of healthcare utilization. PMID- 22042327 TI - Expression and functional analysis of NUCLEAR FACTOR-Y, subunit B genes in barley. AB - NUCLEAR FACTOR-Y, subunit B (NF-YB) comprises a multigene family in plants and has been shown to play important roles in growth, development, and response to environmental stress. In this study, five NF-YBs containing the full-length coding region were obtained from barley (Hordeum vulgare) through database sequence analysis, cloning, and sequencing. Sequence alignment and phylogenetic analysis showed that HvNF-YB3 and HvNF-YB1 were clustered with NF-YB2 and NF-YB3 in Arabidopsis, suggesting these NF-YBs are evolutionary and functionally related. To test this hypothesis, HvNF-YB3 and HvNF-YB1 were overexpressed in Arabidopsis. Overexpression of HvNF-YB1 greatly promoted early flowering in Arabidopsis, supporting that HvNF-YB1may have conserved gene function in flowering time control as NF-YB2 and NF-YB3 in Arabidopsis. Overexpression of HvNF-YB3 in Arabidopsis had no effect on flowering time. An analysis of barley single-nucleotide polymorphism (SNP) data, however, revealed a significant association between an HvNF-YB3 SNP and heading date. While it is unknown whether HvNF-YB3 directly contributes to heading date regulation, the results implied that HvNF-YB3 may also have conserved function in flowering time (heading date in barley) control. Further studies are needed to directly verify these gene functions in barley. Barley NF-YBs showed different expression patterns associated with tissue types, developmental stages, and response to different stress treatments, suggesting that barley NF-YBs may be involved in other physiological processes. PMID- 22042329 TI - Elucidation of structure-function relationships in plant major light-harvesting complex (LHC II) by nonlinear spectroscopy. AB - Conventional linear and time-resolved spectroscopic techniques are often not appropriate to elucidate specific pigment-pigment interactions in light harvesting pigment-protein complexes (LHCs). Nonlinear (laser-) spectroscopic techniques, including nonlinear polarization spectroscopy in the frequency domain (NLPF) as well as step-wise (resonant) and simultaneous (non-resonant) two-photon excitation spectroscopies may be advantageous in this regard. Nonlinear spectroscopies have been used to elucidate substructure(s) of very complex spectra, including analyses of strong excitonic couplings between chlorophylls and of interactions between (bacterio)chlorophylls and "optically dark" states of carotenoids in LHCs, including the major antenna complex of higher plants, LHC II. This article shortly reviews our previous study and outlines perspectives regarding the application of selected nonlinear laser-spectroscopic techniques to disentangle structure-function relationships in LHCs and other pigment-protein complexes. PMID- 22042328 TI - Characterization of StABF1, a stress-responsive bZIP transcription factor from Solanum tuberosum L. that is phosphorylated by StCDPK2 in vitro. AB - ABF/AREB bZIP transcription factors mediate plant abiotic stress responses by regulating the expression of stress-related genes. These proteins bind to the abscisic acid (ABA)-responsive element (ABRE), which is the major cis-acting regulatory sequence in ABA-dependent gene expression. In an effort to understand the molecular mechanisms of abiotic stress resistance in cultivated potato (Solanum tuberosum L.), we have cloned and characterized an ABF/AREB-like transcription factor from potato, named StABF1. The predicted protein shares 45 57% identity with A. thaliana ABFs proteins and 96% identity with the S. lycopersicum SlAREB1 and presents all of the distinctive features of ABF/AREB transcription factors. Furthermore, StABF1 is able to bind to the ABRE in vitro. StABF1 gene is induced in response to ABA, drought, salt stress and cold, suggesting that it might be a key regulator of ABA-dependent stress signaling pathways in cultivated potato. StABF1 is phosphorylated in response to ABA and salt stress in a calcium-dependent manner, and we have identified a potato CDPK isoform (StCDPK2) that phosphorylates StABF1 in vitro. Interestingly, StABF1 expression is increased during tuber development and by tuber-inducing conditions (high sucrose/nitrogen ratio) in leaves. We also found that StABF1 calcium dependent phosphorylation is stimulated by tuber-inducing conditions and inhibited by gibberellic acid, which inhibits tuberization. PMID- 22042330 TI - Probing the topography of the photosystem II oxygen evolving complex: PsbO is required for efficient calcium protection of the manganese cluster against dark inhibition by an artificial reductant. AB - The photosystem II (PSII) manganese-stabilizing protein (PsbO) is known to be the essential PSII extrinsic subunit for stabilization and retention of the Mn and Cl(-) cofactors in the oxygen evolving complex (OEC) of PSII, but its function relative to Ca(2+) is less clear. To obtain a better insight into the relationship, if any, between PsbO and Ca(2+) binding in the OEC, samples with altered PsbO-PSII binding properties were probed for their potential to promote the ability of Ca(2+) to protect the Mn cluster against dark-inhibition by an exogenous artificial reductant, N,N-dimethylhydroxylamine. In the absence of the PsbP and PsbQ extrinsic subunits, Ca(2+) and its surrogates (Sr(2+), Cd(2+)) shield Mn atoms from inhibitory reduction (Kuntzleman et al., Phys Chem Chem Phys 6:4897, 2004). The results presented here show that PsbO exhibits a positive effect on Ca(2+) binding in the OEC by facilitating the ability of the metal to prevent inhibition of activity by the reductant. The data presented here suggest that PsbO may have a role in the formation of the OEC-associated Ca(2+) binding site by promoting the equilibrium between bound and free Ca(2+) that favors the bound metal. PMID- 22042331 TI - A cationic iridium(III) complex showing aggregation-induced phosphorescent emission (AIPE) in the solid state: synthesis, characterization and properties. AB - We report the synthesis and characterization of two cationic iridium(III) complexes with dendritic carbazole ligands as ancillary ligands, namely, [Ir(ppy)(2)L3]PF(6) (1) and [Ir(ppy)(2)L4]PF(6) (2), where L3 and L4 represent 3,8-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)-1,10-phenanthroline and 3,8-bis(3',6' di-tert-butyl-6-(3,6-di-tert-butyl-9H-carbazol-9-yl)-3,9'-bi(9H-carbazol)-9-yl) 1,10-phenanthroline, respectively. Their photophysical properties have been investigated and compared. The results have shown that complex 2 is aggregation induced phosphorescent emission (AIPE) active and exhibits the highest photoluminescent quantum yield (PLQY) of 16.2% in neat film among the reported cationic Ir(III) complexes with AIPE activity. In addition, it also enjoys redox reversibility, good film-forming ability, excellent thermal stability as well as off/on luminescence switching properties, revealing its potential application as a candidate for light-emitting electrochemical cells and organic vapor sensing. To explore applications in biology, 2 was used to image cells. PMID- 22042332 TI - Adaptive alternative splicing correlates with less environmental risk of parkinsonism. AB - BACKGROUND/OBJECTIVE: Environmental exposure to anti-acetylcholinesterases (AChEs) aggravates the risk of Parkinsonism due to currently unclear mechanism(s). We explored the possibility that the brain's capacity to induce a widespread adaptive alternative splicing response to such exposure may be involved. METHODS: Following exposure to the dopaminergic neurotoxin 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP), brain region transcriptome profiles were tested. RESULTS: Changes in transcript profiles, alternative splicing patterns and splicing-related gene categories were identified. Engineered mice over-expressing the protective AChE-R splice variant showed less total changes but more splicing-related ones than hypersensitive AChE-S over-expressors with similarly increased hydrolytic activities. Following MPTP exposure, the substantia nigra and prefrontal cortex (PFC) of both strains showed a nuclear increase in the splicing factor ASF/SF2 protein. Furthermore, intravenous injection with highly purified recombinant human AChE-R changed transcript profiles in the striatum. CONCLUSIONS: Our findings are compatible with the working hypothesis that inherited or acquired alternative splicing deficits may promote parkinsonism, and we propose adaptive alternative splicing as a strategy for attenuating its progression. PMID- 22042333 TI - Significant selective constraint at 4-fold degenerate sites in the avian genome and its consequence for detection of positive selection. AB - A major conclusion from comparative genomics is that many sequences that do not code for proteins are conserved beyond neutral expectations, indicating that they evolve under the influence of purifying selection and are likely to have functional roles. Due to the degeneracy of the genetic code, synonymous sites within protein-coding genes have previously been seen as "silent" with respect to function and thereby invisible to selection. However, there are indications that synonymous sites of vertebrate genomes are also subject to selection and this is not necessarily because of potential codon bias. We used divergence in ancestral repeats as a neutral reference to estimate the constraint on 4-fold degenerate sites of avian genes in a whole-genome approach. In the pairwise comparison of chicken and zebra finch, constraint was estimated at 24-32%. Based on three species alignments of chicken, turkey, and zebra finch, lineage-specific estimates of constraint were 43%, 29%, and 24%, respectively. The finding of significant constraint at 4-fold degenerate sites from data on interspecific divergence was replicated in an analysis of intraspecific diversity in the chicken genome. These observations corroborate recent data from mammalian genomes and call for a reappraisal of the use of synonymous substitution rates as neutral standards in molecular evolutionary analysis, for example, in the use of the well known d(N)/d(S) ratio and in inferences on positive selection. We show by simulations that the rate of false positives in the detection of positively selected genes and sites increases several-fold at the levels of constraint at 4 fold degenerate sites found in this study. PMID- 22042335 TI - [Current state of neoadjuvant therapy principles]. PMID- 22042334 TI - Retrogenes in rice (Oryza sativa L. ssp. japonica) exhibit correlated expression with their source genes. AB - Gene duplication occurs by either DNA- or RNA-based processes; the latter duplicates single genes via retroposition of messenger RNA. The expression of a retroposed gene copy (retrocopy) is expected to be uncorrelated with its source gene because upstream promoter regions are usually not part of the retroposition process. In contrast, DNA-based duplication often encompasses both the coding and the intergenic (promoter) regions; hence, expression is often correlated, at least initially, between DNA-based duplicates. In this study, we identified 150 retrocopies in rice (Oryza sativa L. ssp japonica), most of which represent ancient retroposition events. We measured their expression from high-throughput RNA sequencing (RNAseq) data generated from seven tissues. At least 66% of the retrocopies were expressed but at lower levels than their source genes. However, the tissue specificity of retrogenes was similar to their source genes, and expression between retrocopies and source genes was correlated across tissues. The level of correlation was similar between RNA- and DNA-based duplicates, and they decreased over time at statistically indistinguishable rates. We extended these observations to previously identified retrocopies in Arabidopsis thaliana, suggesting they may be general features of the process of retention of plant retrogenes. PMID- 22042336 TI - Repetitive transcranial magnetic stimulation of motor cortex after stroke: a focused review. AB - Repetitive Transcranial Magnetic Stimulation (rTMS) is known to modulate cortical excitability and has thus been suggested to be a therapeutic approach for improving the efficacy of rehabilitation for motor recovery after stroke. In addition to producing effects on cortical excitability, stroke may affect the balance of transcallosal inhibitory pathways between motor primary areas in both hemispheres: the affected hemisphere (AH) may be disrupted not only by the infarct itself but also by the resulting asymmetric inhibition from the unaffected hemisphere, further reducing the excitability of the AH. Conceptually, therefore, rTMS could be used therapeutically to restore the balance of interhemispheric inhibition after stroke. rTMS has been used in two ways: low frequency stimulation (<=1 Hz) to the motor cortex of the unaffected hemisphere to reduce the excitability of the contralesional hemisphere or high-frequency stimulation (>1 Hz) to the motor cortex of the AH to increase excitability of the ipsilesional hemisphere. The purpose of this systematic review is to collate evidence regarding the safety and efficacy of high-frequency rTMS to the motor cortex of the AH. The studies included investigated the concurrent effects of rTMS on the excitability of corticospinal pathways and upper-limb motor function in adults after stroke. This review suggests that rTMS applied to the AH is a safe technique and could be considered an effective approach for modulating brain function and contributing to motor recovery after stroke. Although the studies included in this review provide important information, double-blinded, sham controlled Phase II and Phase III clinical trials with larger sample sizes are needed to validate this novel therapeutic approach. PMID- 22042337 TI - Can sonoelastography detect plantar fasciitis earlier than traditional B-mode ultrasonography? PMID- 22042338 TI - Radial deviation of distal interphalangeal joint because of overuse of hand pincers tool. PMID- 22042339 TI - Internal and external hemipelvectomy or flail hip in patients with sarcomas: quality-of-life and functional outcomes. AB - OBJECTIVE: We evaluated the quality-of-life of patients who have had an internal hemipelvectomy with and without (flail hip) prosthetic reconstruction and external hemipelvectomy. DESIGN: We reviewed the cases of 15 patients who had undergone either internal or external hemipelvectomy for tumor. Fifteen patients who were previously treated operatively with either a type II periacetabular internal (n = 5) or external (n = 10) hemipelvectomy were evaluated using the Toronto Extremity Salvage Score (TESS), Musculoskeletal Tumor Society (MSTS), and the 36-item Short-Form Health Survey. There were 11 (73%) men and 4 (27%) women in the study, with a mean age at operation of 46.9 +/- 18.0 yrs (range, 18-69 yrs). RESULTS: Follow-up was 30.6 +/- 19.6 mos (range, 6-70 mos). Overall mean MSTS score was 45.2 (range, 6.7 to 83.3), and TESS score was 60.4 +/- 16.1 (range, 31.8-88.0). The 36-item Short-Form Health Survey physical component score results were lower than the general population. TESS and MSTS were all positively correlated to physical component score. There were no significant influences of postsurgery time on MSTS, TESS, or physical component score. Age had a negative correlation with physical function. CONCLUSIONS: Quality-of-life and functional outcome were significantly reduced for patients with internal and external hemipelvectomies on the TESS, MSTS, and the 36-item Short-Form Health Survey physical component scores. PMID- 22042340 TI - Cardiorespiratory function of pediatric heart transplant recipients in the early postoperative period. AB - In this study, we sought to assess the cardiopulmonary functions in three pediatric heart transplant recipients, two of whom are with dilated cardiomyopathy, whereas one is with cyanotic heart disease, in early postoperative period. Cardiopulmonary exercise testing was performed using an incremental cycling at 1 mo after surgery. The results revealed that our study subjects had obvious impairment in workload, oxygen consumption, and oxygen pulse at peak exercise and ventilatory threshold at 1 mo after orthotropic heart transplantation. The pediatric orthotropic heart transplantation recipients also showed a high resting heart rate (90-106 beats/min), a low peak heart rate (109 117 beats/min) during exercise, and continuous heart rate acceleration till 1 to 3 mins after the cessation of exercise. In conclusion, pediatric orthotropic heart transplant recipients have a low cardiopulmonary endurance during the early postoperative period. An early structured, individualized cardiopulmonary rehabilitation program for pediatric orthotropic heart transplant recipients will be an area for future evaluation and research. PMID- 22042341 TI - Synthesis and biological evaluation of potential new inhibitors of the bacterial transferase MraY with a beta-ketophosphonate structure. AB - Stable analogs of bacterial transferase MraY substrate or product with a pyrophosphate surrogate in their structure are described. beta-ketophosphonates were designed as pyrophosphate bioisosteres and were investigated as UDP-GlcNAc mimics. The developed strategy allows introduction of structural diversity at a late stage of the synthesis. The biological activity of the synthesized compounds was evaluated on the MraY enzyme. PMID- 22042342 TI - [Prof. Heonir Rocha 2011 Prize]. PMID- 22042343 TI - [In memoriam: Professor Jose Silverio Santos Diniz (1935-2011)]. AB - Professor Jose Silverio Santos Diniz, an exponent of the Brazilian Pediatric Nephrology, died on 23 May, 2011. This editorial is a brief description of the career of this great Brazilian teacher, physician and researcher. PMID- 22042344 TI - [Evaluation of dental insertion loss in patients with chronic kidney disease]. AB - Chronic kidney failure (CKF) is a clinical syndrome due to the slow, progressive and irreversible loss of the glomerular filtration rate. CKF may be associated with several oral manifestations, such as xerostomia, uremic stomatitis and periodontitis, diagnosed as clinical attachment loss (CAL). 92 patients, from the Prontorim Hemodialysis Clinic of Fortaleza, Ceara, Brazil, were investigated. Only 34 patients (37%) were eligible for periodontal investigation, which consisted of CAL measurement (values grater than 2 mm diagnosing periodontitis). CAL measurements ranged from 1.31 to 5.27 mm (2.30 +/- 0.96 mm). 18 (52.9%) patients had smaller than 2 mm CAL, while 16 (47.1%) had periodontitis. Tooth loss and considerable CAL were observed in this study. Nevertheless, factors such as social status should be considered in further investigations. PMID- 22042345 TI - [Demographic, clinical and laboratory data of patients with urinary lithiasis in Fortaleza, Ceara]. AB - OBJECTIVE: To describe the demographic, clinical and laboratory data of patients with urolithiasis in Fortaleza, Ceara, Brazil. PATIENTS AND METHODS: Secondary data were collected from the medical records of 197 patients with urolithiasis, during the period 1996-2006. Clinical evaluation and 24-h urine collection for measurements of urinary volume, creatinine, calcium, phosphorous, uric acid, sodium, potassium and magnesium were performed. Density and pH value were determined in a first-voided morning urine sample. Cystinuria was detected by stone and/or crystal analysis. RESULTS: The male/female ratio was 1:1.7. The average age of symptom onset was 35.8 +/- 13.3 years, with no significant difference between the genders. The most affected age range was 20-39 years (56.3%). Patients reported renal colic (72.4%), emergency room attendance (69.5%), a single episode of lithiasis (46.7%) or recurrent episodes (53.3%). The right kidney was most often affected in women (44.4%), while men suffered predominantly from bilateral lithiasis (39.7%). The main metabolic changes observed were hypernatriuria (80.7%), hypercalciuria (48.7%), hyperuricosuria (17.3%), and cystinuria in 5 patients (2.5%). The average pH value and density were 5.74 +/- 0.59 and 1015.6 +/- 7.1, respectively. Urinary volume was low in 43% of the cases. CONCLUSION: Lithiasis was most prevalent in adults aged 20-39 years, and affected predominantly women in our region. The most frequent metabolic changes, in descending order, were hypernatriuria, followed by hypercalciuria and hyperuricosuria, associated with low fluid intake. PMID- 22042346 TI - [Factors related to interdialytic weight gain in hemodialysis patients]. AB - INTRODUCTION: Studies have shown that interdialytic weight gain (IDWG) of hemodialysis (HD) patients is influenced by many factors, a high IDWG negatively affecting the blood pressure (BP) of this population. OBJECTIVE: To evaluate the relation of clinical, demographic and nutritional factors and the IDWG of HD patients. METHODS: Cross-sectional study of 278 HD (54% males; age=54.4 +/- 14.4 years) from 6 dialysis centers in the State of Santa Catarina, Brazil. The means of percentage interdialytic weight gain (%IDWG) and BP during a four-week period were calculated. Body mass index (BMI) and the 7-point subjective global assessment (SGA) scale were used to assess nutritional status. RESULTS: The means were: %IDWG 4.06 +/- 1.55%, pre-HD BP 140 +/- 50 / 99 +/- 25 mmHg, and post-HD BP 110 +/- 27 / 78 +/- 10 mmHg. %IDWG inversely correlated with age and BMI and directly correlated with pre-HD systolic BP and time on HD. Women and patients without diabetes mellitus had higher %IDWG. Only the younger subgroup of patients with SGA-defined malnutrition had higher %IDWG than well-nourished ones. When malnutrition was BMI-defined, higher %IDWG was found in the whole study population and in the female and younger age subgroups. 24% of the patients had increased %IDWG (> 5%) and, when compared with those with adequate %IDWG, had inadequate and higher levels of systolic BP (144 +/- 21 versus 138 +/- 20 mmHg, p < 0.05), were younger and had lower BMI. CONCLUSION: These results showed that %IDWG of HD patients was influenced by gender, time on dialysis, age and nutritional status, and that high %IDWG adversely affected the BP of this population. PMID- 22042347 TI - Are serum cystatin C levels influenced by steroid doses in lupus nephritis patients? AB - INTRODUCTION: Cystatin C is considered a promising test to evaluate glomerular filtration rate, since it has characteristics of an ideal endogenous marker, being similar or even superior to serum creatinine according to some studies. However, it is possible that some factors (as corticotherapy) could have an influence on serum cystatin C levels regardless of the glomerular filtration rate. The aim of this study was to investigate if different doses of glucocorticoid could have an influence on serum cystatin C levels in lupus nephritis patients. METHODS: We evaluated 42 patients with lupus nephritis that performed 109 different blood collections; their mean age was 37.7 +/- 13.1 years old, and 88% were female; the mean estimated glomerular filtration rate was of 61.9 +/- 20.0 mL/min. Patients were divided according to their glucocorticoid dose in two groups: A - high (pulse therapy with methylprednisolone and prednisone > 0.5 mg/kg/d, n = 14) versus B - low doses (prednisone <= 0.5 mg/kg/d, n = 28). Serum creatinine levels were used as parameters for renal function comparison. Cystatin C was determined by an in-house methodology, using Luminex system flow citometry. RESULTS: Considering these groups, cystatin C levels were different only in the second visit (p = 0.106). But, when the serum creatinine levels were considered in the same groups, a marginally significant difference among them (p = 0.070) was observed, which suggested that the difference in cystatin C levels between the groups was caused by their respective glomerular filtration rate. There was not any difference between those groups that received or did not receive pulse therapy. CONCLUSION: Although some previous studies have shown that glucocorticoid has an influence on serum cystatin C levels, we have not observed such interference in the lupus nephritis patients submitted to corticotherapy. PMID- 22042349 TI - [Clinical and laboratorial characteristics associated with biopsy proved hypertensive nephroangiosclerosis]. AB - INTRODUCTION: Hypertensive nephroangiosclerosis is a major cause of chronic kidney disease requiring dialysis. Clinical characteristics that distinguish a patient with hypertension that evolves to nephroangiosclerosis from another that keeps stable renal function are not well established because of the difficulty in ensuring that the carriers of that disease are not actually suffering from glomerulonephritis or other kidney diseases. Thus, our objective was to identify clinical or laboratory features that distinguish the patients who developed chronic renal failure from hypertension, confirmed by renal biopsy, of those who, even with arterial hypertension, did not develop nephroangiosclerosis. METHODS: We conducted a retrospective comparison of clinical and laboratory data of 15 patients with hypertensive nephroangiosclerosis confirmed by renal biopsy and 15 hypertensive patients from the outpatient clinic of the Hypertension Center, whose lack of nephroangiosclerosis was defined as absence of proteinuria. The groups were matched for age and gender. RESULTS: Among the evaluated variables, duration of hypertension, pulse pressure, blood glucose, uric acid, creatinine and frequency of use of diuretics and sympatholytic differed statistically between the two groups. All these variables were higher in nephroangiosclerosis patients. CONCLUSION: This study links biopsy proven hypertensive nephroangiosclerosis with metabolic features, hypertension intensity and duration, corroborating the idea that primary prevention of hypertension, postponing its initiation, a more intensive hemodynamic control (when hypertension is well established) and metabolic control of these patients have the potential to prevent hypertensive nephroangiosclerosis. PMID- 22042348 TI - [The value of Cockcroft-Gault equation for the screening of decreased renal function in patients with systemic arterial hypertension]. AB - INTRODUCTION: Arterial hypertension is a worldwide public health problem and one of the major risk factors for chronic kidney disease development. METHODS: In order to compare the Cockcroft-Gault (CG) equation with serum creatinine and 24 hour creatinine clearance (CrCl) for the screening of reduced renal function, a cross-sectional study of 198 hypertensive patients was undertaken at a basic health unit. The demographic, nutritional, and clinical laboratory data were analyzed. Renal function was assessed by serum creatinine and 24hour CrCl. Glomerular filtration rate (GFR) was also estimated according to Cockcroft-Gault equation. RESULTS: The patients had a mean age of 60.6 +/- 11.6 years-old, and 73.7% were female. The prevalence of serum creatinine > 1.2 mg/dL was 7.6% and the prevalence of GFR < 60 mL/minute was 24.2%, when evaluated by the CrCl and CG equation. Reduced GFR was observed in older male patients, with lower body mass index, normal values of fasting blood glucose, and higher levels of serum uric acid and of systolic blood pressure. DISCUSSION: The prevalence of decreased renal function among hypertensive patients varies considerably, depending on the laboratory investigation used. CG-estimated CrCl has shown to be more accurate than serum creatinine for assessing GFR. CONCLUSIONS: CG-estimated CrCl was highly similar to 24-hour CrCl, proving to be a reliable primary care screening test for the early diagnosis of renal impairment in hypertensives. PMID- 22042350 TI - Clinical and pathological correlations of C4d immunostaining and its influence on the outcome of kidney transplant recipients. AB - INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31%) biopsies, of which 23 (14.7%) had diffuse and 25 (16%) focal distribution. Pre-transplantation panel reactive antibodies (%PRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d-, patients with ABMR C4d+ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high %PRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation. PMID- 22042351 TI - [Effects of the overlapping between an experimental model of neuroendocrine obesity with arterial hypertension under blood pressure, body weight and metabolic and renal parameters in rats]. AB - INTRODUCTION: Increased body mass index and the metabolic syndrome are associated with decreased renal function and the development of end-stage kidney disease. OBJECTIVE: To evaluate the effect of the overlap between an experimental model of obesity and genetic hypertension on the blood pressure, body weight and metabolic and kidney parameters of rats. METHODS: We studied male rats of the Wistar (WST) and spontaneously hypertensive rats (SHR) strains. Monosodium glutamate (MSG) was administered in the neonatal period to both strains, to make up two groups: WST + MSG and SHR + MSG. Animals in the control groups (WST and SHR) received saline. After completing three months of life, a 12-week follow-up period ensued, during which bi-weekly measurements of body weight (BW) and tail-cuff blood pressure (TCBP) were obtained. Microalbuminuria was analyzed at weeks 0, 4, 8 and 12. At the end of the follow-up period, blood was obtained for fasting glucose, plasma creatinine, and lipid profile determinations. The kidneys were removed, stained, and the glomerular sclerosis index was calculated. RESULTS: The administration of MSG produced higher percentage body weight gain, higher fasting blood glucose and a higher degree of glomerular injury in WST-MSG and MSG-SHR rats, compared to their controls. Greater urinary albumin excretion was observed in SHR + MSG rats, when compared to SHR. There was no statistical difference in the TCBP, creatinine, and lipid profile. CONCLUSIONS: The association of neuroendocrine obesity and arterial hypertension promoted morphological and functional changes in the glomerulus. These changes were more severe than those observed in hypertensive-only rats. PMID- 22042352 TI - [Ten-year follow-up of kidney transplantation with living unrelated donor]. AB - INTRODUCTION: In the current era of scarcity of kidneys available for transplantation, and chronic anti-HLA-mediated rejection as a main cause of graft loss, continuous demonstration of the long-term survival of grafts from living unrelated kidney donors (LURD) is paramount. OBJECTIVE: Analyze long-term kidney graft and patient outcomes using LURD, and compare them with living related donors (LRD). METHODS: We analyzed the 389 first renal transplantations performed with a living donor (281 LRD and 108 LURD), in a single center, from January 1998 through December 2007. RESULTS: There were no significant differences between LRD and LURD as refers to patient survival (89.1% vs. 84.7%, p = 0.40, respectively) and graft survival (81.1% vs. 68.9%, p = 0.77, respectively), 10 years post transplantation. On Cox proportional regression model of multivariate analysis, panel reactive antibodies (PRA) > 10% and the occurrence of acute rejection in the first year posttransplantation were the only independent predictors of graft loss (HR 2.54, 95% CI 1.35 -4.78; p < 0.05 and HR 4.1, 95% CI 2.04 - 4.78; p < 0.05, respectively). CONCLUSION: LURD are an important source of organs for renal transplantation, with results similar to those obtained with LRD, regardless of HLA matching. PMID- 22042353 TI - [Inflammation in chronic kidney disease: the role of cytokines]. AB - Chronic kidney disease (CKD) is a serious public health problem whose prevalence has increased in the last few years. Its progression is associated with high morbidity and mortality. Several factors are associated with the onset and progression of CKD, such as obesity, hypertension and diabetes mellitus. Beyond these factors, there is evidence of a pathophysiological role for inflammation in CKD. Several cytokines and chemokines have been detected in the plasma and urine of patients at early stages of CKD, and have also been related to CKD complications. The expression of these mediators and renal injury may be influenced by drugs such as angiotensin-converting enzyme inhibitors, statins and antagonists of cytokine receptors. Modulation of the immune-inflammatory response can become a target for CKD treatment. The aim of this study was to review the scientific evidence on the role of inflammation in CKD, especially the effects of cytokines and chemokines. PMID- 22042354 TI - [V Brazilian guidelines for ambulatory monitoring of arterial pressure and III Brazilian guidelines for home monitoring of blood pressure]. PMID- 22042355 TI - Hepatitis B vaccination in hemodialysis patients: different points of view for conclusion. AB - The present letter to the editor shows the other aspect of Hepatitis B vaccination in hemodialysis patients. PMID- 22042357 TI - Association between body mass index and asthma among Japanese adults: risk within the normal weight range. AB - BACKGROUND: Increasing amounts of data have shown that some Asian populations are more susceptible to increased weight and development of noncommunicable disease than Western populations. However, little is known about the association between increased weight, particularly within the normal range, and the development of asthma among Asian populations. METHODS: To examine the association between increased body mass index (BMI) and asthma among Japanese adults, data from a nationwide population-based cross-sectional survey of asthma prevalence in Japan were analyzed (n = 22,962; age range 20-79 years). BMIs were classified into 7 categories considering WHO recommendations (cutoff points: 17.00, 18.50, 23.00, 25.00, 27.50 and 30.00), and the association between BMI and the prevalences of asthma as well as asthma symptoms were assessed by multivariate logistic regression. RESULTS: The prevalences of obesity (BMI >= 30.00) in this population were relatively low (males 3.0%, females 2.3%). BMI categories of 25.00 or higher in both genders were significantly associated with an increased risk of asthma compared with the reference category (BMI 18.50-22.99). Even in females with a BMI of 23.00-24.99, the prevalence of asthma significantly increased (adjusted odds ratio 1.49, 95% confidence interval 1.16-1.92) compared with that in the reference category. CONCLUSIONS: An increase in the prevalence of asthma among Japanese females starts at a BMI of 23.00, which was relatively lower than those reported from Western countries. This finding suggests that the Japanese population is likely to have asthma with a lesser degree of obesity than Western populations. PMID- 22042358 TI - Breast reshaping with dermaglandular flaps after giant lipoma removal: versatility of oncoplastic techniques. AB - Lipomas of the breast are benign lesions that do not raise great interest in the literature and their incidence is unclear. They usually are small, benign soft tissue tumors of fat cells that can be treated by simple excision. Although lipoma is a banal condition, it often causes diagnostic and therapeutic uncertainty. The first reason for this is the normal fatty composition of the breast. Second, it may be difficult to distinguish a lipoma from other benign or malignant lumps. This report presents a rare case involving giant lipoma of the breast that compromised most of the mass of the breast. After resection, the remaining breast was reshaped using multiple dermaglandular flaps to restore the breast mound, and contralateral breast mammaplasty was performed for symmetry. This case is a good illustration of the oncoplastic reconstruction options available after wide local excision. PMID- 22042359 TI - Synergistic effects of cryolipolysis and shock waves for noninvasive body contouring. AB - BACKGROUND: Excess body fat, localized adiposity, and cellulite represent important social problems. To date, techniques using radiofrequencies, cavitation and noncavitation ultrasound, and carbon dioxide have been studied as treatments for noninvasive body contouring. Ice-Shock Lipolysis is a new noninvasive procedure for reducing subcutaneous fat volume and fibrous cellulite in areas that normally would be treated by liposuction. It uses a combination of acoustic waves and cryolipolysis. Shock waves, used normally in the treatment of renal calculi and musculoskeletal disorders, are focused on the collagen structure of cellulite-afflicted skin. When used on the skin and underlying fat, they cause a remodeling of the collagen fibers, improving the orange-peel appearance typical of the condition. Cryolipolysis, on the other hand, is a noninvasive method used for the localized destruction of subcutaneous adipocytes, with no effects on lipid or liver marker levels in the bloodstream. The combination of the two procedures causes the programmed death and slow resorption of destroyed adipocytes. METHODS: In this study, 50 patients with localized fat and cellulite were treated with a selective protocol for the simultaneous use of two transducers: a Freezing Probe for localized fatty tissue and a Shock Probe for fibrous cellulite. RESULTS: The procedure significantly reduced the circumference in the treated areas, significantly diminishing fat thickness. The mean reduction in fat thickness after treatments was 3.02 cm. Circumference was reduced by a mean of 4.45 cm. Weight was unchanged during the treatment, and no adverse effects were observed. Histologic and immunohistochemical analysis confirmed a gradual reduction of fat tissue by programmed cell death. Moreover, the reduction in fat thickness was accompanied by a significant improvement in microcirculation, and thus, the cellulite. The safety of the method also has been highlighted because it is accompanied by no significant increase in serum liver enzymes or serum lipids. CONCLUSION: The study aimed to observe the effects of the new technique in the treatment of localized fat associated with cellulite in order to assess adipose tissue alterations, cellular apoptosis, and levels of serum lipid or liver markers. The findings show that the action of Ice-Shock Lipolysis is a safe, effective, and well-tolerated noninvasive procedure for body contouring. In particular, the authors believe that this could be an ideal alternative to liposuction for patients who require only small or moderate amounts of adipose tissue and cellulite removal or are not suitable candidates for surgical approaches to body contouring. PMID- 22042360 TI - Patients have a right to safe surgery. PMID- 22042361 TI - Recording large-scale neuronal ensembles with silicon probes in the anesthetized rat. AB - Large scale electrophysiological recordings from neuronal ensembles offer the opportunity to investigate how the brain orchestrates the wide variety of behaviors from the spiking activity of its neurons. One of the most effective methods to monitor spiking activity from a large number of neurons in multiple local neuronal circuits simultaneously is by using silicon electrode arrays. Action potentials produce large transmembrane voltage changes in the vicinity of cell somata. These output signals can be measured by placing a conductor in close proximity of a neuron. If there are many active (spiking) neurons in the vicinity of the tip, the electrode records combined signal from all of them, where contribution of a single neuron is weighted by its 'electrical distance'. Silicon probes are ideal recording electrodes to monitor multiple neurons because of a large number of recording sites (+64) and a small volume. Furthermore, multiple sites can be arranged over a distance of millimeters, thus allowing for the simultaneous recordings of neuronal activity in the various cortical layers or in multiple cortical columns (Fig. 1). Importantly, the geometrically precise distribution of the recording sites also allows for the determination of the spatial relationship of the isolated single neurons. Here, we describe an acute, large-scale neuronal recording from the left and right forelimb somatosensory cortex simultaneously in an anesthetized rat with silicon probes (Fig. 2). PMID- 22042362 TI - Epigenetic silencing of the tumor suppressor klotho in human breast cancer. AB - Klotho is a single pass transmembrane protein, associated with premature aging. We identified tumor suppressor activities for klotho, associated with reduced expression in breast cancer. We now aimed to analyze klotho expression in early stages of breast tumorigenesis and elucidate mechanisms leading to klotho silencing in breast tumors. We studied klotho expression, using immunohistochemistry, and found high klotho expression in all normal and mild hyperplasia samples, whereas reduced expression was associated with moderate and atypical ductal hyperplasia. Promoter methylation and histone deacetylation were studied as possible mechanisms for klotho silencing. Using bisulfite sequencing, and methylation-specific PCR, we identified KLOTHO promoter methylation in five breast cancer cell lines and in hyperplastic MCF-12A cells, but not in the non tumorous mammary cell line HB2. Importantly, methylation status inversely correlated with klotho mRNA levels, and treatment of breast caner cells with 5 aza-2-deoxycytidine elevated klotho expression by up to 150-fold. KLOTHO promoter methylation was detected in 8/23 of breast cancer samples but not in normal breast samples. Chromatin immunoprecipitation revealed that in HB2 KLOTHO promoter was enriched with AcH3K9; however, in breast cancer cells, H3K9 was deacetylated, and treatment with the histone deacetylase inhibitor suberoylanilide bishydroxamide (SAHA) restored H3K9 acetylation. Taken together, these data indicate loss of klotho expression as an early event in breast cancer development, and suggest a role for DNA methylation and histone deacetylation in klotho silencing. Klotho expression and methylation may, therefore, serve as early markers for breast tumorigenesis. PMID- 22042363 TI - Women's features and inter-/intra-rater agreement on mammographic density assessment in full-field digital mammograms (DDM-SPAIN). AB - Measurement of mammographic density (MD), one of the leading risk factors for breast cancer, still relies on subjective assessment. However, the consistency of MD measurement in full-digital mammograms has yet to be evaluated. We studied inter- and intra-rater agreement with respect to estimation of breast density in full-digital mammograms, and tested whether any of the women's characteristics might have some influence on them. After an initial training period, three experienced radiologists estimated MD using Boyd scale in a left breast cranio caudal mammogram of 1,431 women, recruited at three Spanish screening centres. A subgroup of 50 randomly selected images was read twice to estimate short-term intra-rater agreement. In addition, a reading of 1,428 of the images, performed 2 years before by one rater, was used to estimate long-term intra-rater agreement. Pair-wise weighted kappas with 95% bootstrap confidence intervals were calculated. Dichotomous variables were defined to identify mammograms in which any rater disagreed with other raters or with his/her own assessment, respectively. The association between disagreement and women's characteristics was tested using multivariate mixed logistic models, including centre as a random effects term, and taking into account repeated measures when required. All quadratic-weighted kappa values for inter- and intra-rater agreement were excellent (higher than 0.80). None of the studied women's features, i.e. body mass index, brassiere size, menopause, nulliparity, lactation or current hormonal therapy, was associated with higher risk of inter- or intra-rater disagreement. However, raters differed significantly more in images that were classified in the higher-density MD categories, and disagreement in intra-rater assessment was also lower in low-density mammograms. The reliability of MD assessment in full-field digital mammograms is comparable to that for original or digitised images. The reassuring lack of association between subjects' MD-related characteristics and agreement suggests that bias from this source is unlikely. PMID- 22042364 TI - Comparison between screen-detected and symptomatic breast cancers according to molecular subtypes. AB - Breast cancer screening programs make it possible to detect early cancer, thus reducing breast cancer mortality. We studied the clinicopathologic characteristics and prognosis of screen-detected invasive breast cancer compared with symptomatic breast cancer. And we compared the result according to molecular subtypes (luminal A, luminal B, Her2, and triple negative), with the goal of identifying the role of screening in each subtypes. From January 2002 to June 2008, 3,141 patients who underwent surgery for the treatment of invasive ductal carcinoma at Samsung Medical Center were included. Among them, 1,025 patients were screen-detected, and 2,116 patients who were screened over 2 years or never were symptomatic. We retrospectively reviewed the clinical and pathologic data. Screen-detected breast cancer was associated with older age, smaller tumor size, more hormone-receptor positive, less lymph node involvement, earlier stage, and reduced mortality compared with symptomatic breast cancer (P < 0.001). According to the molecular subtype, luminal A was most common (63.6%) and showed the most obvious survival benefit in screen-detected tumors in comparison with symptomatic tumors (5-year OS: 99.7 vs. 96.5%, 5-year DFS: 96.4 vs. 90.7%). Screen detection was independently associated with improved overall and disease-free survival outcomes after adjustment for covariates (HR 0.32, P = 0.035; HR 0.58, P = 0.020, respectively) only in the luminal A subtype. Differences in pathological features such as tumor size, nodal status, grade, and age at diagnosis with different molecular subtype distributions may explain the survival advantage of patients with screen-detected breast cancer. Screening programs seem to have a different efficacy depending on the molecular subtype of the breast cancer, especially in the luminal A subtype, for which screen detection acts as an independent prognostic factor itself. PMID- 22042365 TI - Rates of upgrade to malignancy for 271 cases of flat epithelial atypia (FEA) diagnosed by breast core biopsy. AB - Flat epithelial atypia (FEA) is a borderline lesion that might represent an early stage in the development of certain low-grade carcinomas in situ and invasive cancers. There are no guidelines on its management. Our objectives were to determine the upgrade to malignancy rate and identify a subpopulation of patients that might undergo just mammographic surveillance. We retrospectively reviewed the data for 271 FEA cases among 5,555 breast core biopsies obtained over a 7 year period (January 2003-2010). We collated clinical data (age, history of cancer, menopausal status), radiological data (lesion type, size, Bi-Rads category), technical data (number of biopsies, needle gauge, excision quality) and histological data and sought correlations between these factors and upgrade rate. The 271 FEA comprised 128 cases of pure FEA, 135 cases of FEA + atypical ductal hyperplasia, and 8 cases of FEA + atypical lobular hyperplasia. Overall, 184 patients underwent surgery and 46 mammographic surveillance. Surgery detected 34 cases of malignancy (23 CIS, 7 invasive cancers, and 4 mixed cases) giving a 15% upgrade rate. Quality of excision was the only factor associated with under diagnosis. The presence of FEA at biopsy warrants surgery. PMID- 22042366 TI - Chromosome 17 centromere (CEP17) duplication as a predictor of anthracycline response: evidence from the NCIC Clinical Trials Group (NCIC CTG) MA.5 Trial. AB - HER2 gene amplification and topoisomerase IIalpha gene (TOP2A) alteration have been associated with increased benefit from anthracycline compared to non anthracycline containing adjuvant breast cancer chemotherapy in some but not other studies. Chromosome 17 centromere (CEP17) duplication was measured on TMAs from formalin-fixed paraffin-embedded specimens obtained from 639 of 716 premenopausal women with node positive breast cancer who received cyclophosphamide, epirubicin and fluorouracil (CEF) or cyclophosphamide, methotrexate and fluorouracil (CMF) in the randomized controlled mammary 5 (MA.5) adjuvant trial. The prognostic impact of CEP17 duplication and its interactions with treatment were studied for relapse-free survival (RFS) and overall survival (OS). Overall, CEP17 duplication was not significantly associated with RFS or OS in multivariate analysis. For patients whose tumours had normal CEP17 copy number there were no apparent benefits for CEF compared to CMF for RFS (HR 0.98; 95% CI 0.68-1.42) or OS (HR 1.10; 95% CI 0.72-1.69). For patients whose tumours had CEP17 duplication, there was significant benefit for CEF compared to CMF for RFS (HR 0.54; CI 0.33-0.89) and a trend towards significance for OS (HR 0.64; CI 0.37 1.09). The adjusted P values for interaction between treatment and CEP17 duplication were 0.09 for RFS and 0.13 for OS. This study suggests that CEP17 duplication has a borderline association with clinical responsiveness to anthracycline containing chemotherapy similar to previous results seen with HER2 amplification and TOP2A alteration in MA.5. An appropriately powered meta analysis is required to discriminate the predictive value of these three candidate markers. PMID- 22042367 TI - Epstein-Barr virus is seldom found in mammary epithelium of breast cancer tissue using in situ molecular methods. AB - Epstein-Barr virus (EBV) has been proposed as a possible etiological agent of breast cancer based on 21 reports of EBV in malignant breast tissues. Most of these studies used standard and nested solution polymerase chain reaction (PCR) techniques, both disadvantaged by susceptibility to contamination from laboratory EBV, and the inability to localize the signal to a specific cell type. To avoid these issues, we used in situ molecular methods of viral detection to reassess the frequency of EBV in malignant breast tissue. We used a commercial in situ hybridization (ISH) system with an EBER genome target, and a non-commercial in situ PCR (IS-PCR) method using primers specific for the BamH1 region. The assays were performed on malignant breast tissue sections from 70 breast cancer patients at the M. D. Anderson Cancer Center, Houston, TX. EBV was found in mammary epithelial cells, the cell type from which most breast cancers arise, in 2/70 (2.9%) of specimens using IS-PCR and in none of the specimens using ISH. Based on these findings that EBV was present in human mammary epithelial cells so infrequently, it is unlikely to play a causative role in most types of breast cancer. PMID- 22042368 TI - Comparison of breast cancer recurrence risk and cardiovascular disease incidence risk among postmenopausal women with breast cancer. AB - The majority of breast cancers are diagnosed in postmenopausal women. Competing comorbidities, particularly cardiovascular disease (CVD), should be considered when individualizing adjuvant therapies for these women. We compared the 10-year predicted breast cancer recurrence risk with CVD risk among postmenopausal women with hormone receptor-positive (HR+), non-metastatic breast cancer. CVD risk factor data were prospectively collected from postmenopausal women with stage I III, HR+ breast cancer initiating adjuvant aromatase inhibitor therapy. We compared predicted 10-year CVD risk, including the composite index heart age, computed from modified Framingham risk score, with predicted 10-year risk of breast cancer recurrence using Adjuvant! Online. We created multivariable logistic regression models to estimate the odds ratios (OR) and 95% confidence intervals (CI) for greater CVD risk than breast cancer recurrence risk. Among 415 women, mean age and heart age were 60 and 67 years, respectively. Overall, 43% of women had a predicted 10-year CVD risk equivalent to breast cancer recurrence risk and 37% had CVD risk higher than breast cancer recurrence risk. Predicted CVD risk was higher than breast cancer recurrence risk for stage I disease (OR: 6.1, 95% CI: 3.4-11.2) or heart age >65 (OR: 12.4, 95% CI: 7.0-22.6). The majority of postmenopausal women with HR+ early breast cancer had a predicted 10 year CVD risk that was equivalent to or higher than breast cancer recurrence risk. Physicians should weigh competing risks and offer early screening and cardiac prevention strategies for women at a greater risk for CVD. PMID- 22042369 TI - Triggering of Toll-like receptor 4 on metastatic breast cancer cells promotes alphavbeta3-mediated adhesion and invasive migration. AB - Triggering of Toll-like receptor 4 (TLR4) on tumor cells has been found to promote tumor progression by promoting tumor cell proliferation and survival. So far, however, the effect of TLR4 signaling on tumor metastasis has not been well elucidated. Here, we report that triggering of TLR4 on metastatic breast cancer cells could reciprocally regulate the expression of alphavbeta3 and the expressions of TPM1 and maspin, and promote alphavbeta3-mediated adhesion and invasive migration of the cells. In metastatic breast cancer cells, TLR4 signaling increased the expression of integrin alphavbeta3 by activating NF kappaB, resulting in the increased adhesion capacity of tumor cells to the ligand for alphavbeta3, and the increased polymerization of actin and production of MMP 9 in tumor cells in response to ECM. HoxD3 was required for the up-regulation of alphav and beta3 expressions by NF-kappaB. Moreover, TLR4 signaling increased the expression of miR-21 in breast cancer cells by activating NF-kappaB. Accordingly, the expressions of TPM1 and maspin were decreased at protein level, whereas the transcription activity of these genes was not influenced. Consistent with the promoting effect on alphavbeta3-mediated adhesion and invasive migration, TLR4 signaling promoted the arrest of metastatic breast cancer cells in circulation and following invasion. The effect of TLR4 signaling could be abrogated by inhibiting NF-kappaB. These findings suggest that metastatic breast cancer cells could acquire higher metastatic potential due to triggering of TLR4 and activation of NF-kappaB in the cells, and that both TLR4 and NF-kappaB could be therapeutic targets for preventing metastasis of breast cancer cells. PMID- 22042370 TI - A plea for the biopsy marker: how, why and why not clipping after breast biopsy? AB - In the last decade, percutaneous breast biopsies have become a standard for the management of breast diseases. Biopsy clips allow for precise lesion localization, thus minimizing the volume of breast to be resected at the time of surgery. With the development of many imaging techniques (including mammography, sonography, and breast magnetic resonance imaging), one of the challenges of the multidisciplinary became to synthesize all informations obtained from the various imaging procedures. The use of biopsy markers after percutaneous biopsy is one of the keys for optimal patient management, helping the radiologist to deal with multiple lesions, to insure correlation across different imaging modalities and to follow-up benign lesions, helping the oncologist by marking a tumor prior to neoadjuvant chemotherapy, helping the surgeon by facilitating preoperative needle localization, to precisely mark the margins of extensive disease and to guide intraoperative tumor resection, and helping the pathologist to insure the lesion of interest has been removed and to identify the region of interest in a mastectomy specimen. We believe biopsy clip markers should be deployed after all percutaneous interventions and present in this review the arguments to support this statement. Minimal indications for clip deployment will also be detailed. PMID- 22042371 TI - Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone women's health initiative clinical trials. AB - The associations between breast tenderness during use of conjugated equine estrogen (CEE) therapy with or without medroxyprogesterone (MPA) therapy and subsequent breast cancer risk are unknown. We analyzed data from the Women's Health Initiative Estrogen plus Progestin (N = 16,608, 5.6 years intervention) and estrogen-alone (N = 10,739, 6.8 years intervention) clinical trials until trial close-out (Spring 2005). At baseline and annually, participants underwent mammography and clinical breast exam. Self-reported breast tenderness was assessed at baseline and 12 months. Invasive breast cancer was confirmed by medical record review. The risk of new-onset breast tenderness after 12 months was significantly higher among women assigned to active therapy than placebo (CEE alone vs. placebo risk ratio [RR] 2.15, 95% confidence interval [CI] 1.97-2.35; CEE + MPA vs. placebo RR 3.07, 95% CI 2.85-3.30). CEE + MPA doubled the risk of invasive breast cancer among women with baseline breast tenderness (hazard ratio [HR] 2.16, 95% CI 1.29-3.74), but had a smaller effect among women without baseline breast tenderness (HR 1.17; 95% CI 0.97-1.41). New-onset breast tenderness was associated with a higher risk of breast cancer among women assigned to CEE + MPA (HR 1.33, 95% CI 1.02-1.72, P = 0.03), but not among women assigned to CEE-alone (HR 0.98, 95% CI 0.62-1.53). New-onset breast tenderness during use of CEE + MPA was associated with increased subsequent breast cancer risk. The association of CEE + MPA therapy with increased breast cancer risk was especially pronounced among women with baseline breast tenderness. PMID- 22042372 TI - A phase I/II prospective, single arm trial of gefitinib, trastuzumab, and docetaxel in patients with stage IV HER-2 positive metastatic breast cancer. AB - Inhibition of the HER-2 pathway via the monoclonal antibody trastuzumab has had a major impact in treatment of HER-2 positive breast cancer, but de novo or acquired resistance may reduce its effectiveness. The known interplay between the epidermal growth factor receptor (EGFR) and HER-2 receptors and pathways creates a rationale for combined anti-EGFR and anti-HER-2 therapy in HER-2 positive metastatic breast cancer (MBC), and toxicities associated with the use of multiple chemotherapeutic agents together with biological therapies may also be reduced. We conducted a prospective, single arm, phase I/II trial to determine the efficacy and toxicity of the combination of trastuzumab with the EGFR inhibitor gefitinib and docetaxel, in patients with HER-2 positive MBC. The maximum tolerated dose (MTD) was determined in the phase I portion. The primary end point of the phase II portion was progression-free survival (PFS). Immunohistochemical analysis of biomarker expression of the PKA-related proteins cAMP response element-binding protein (CREB), phospho-CREB and DARPP-32 (dopamine and cAMP-regulated phosphoprotein of 32 kDa) plus t-DARPP (the truncated isoform of DARPP-32); PTEN; p-p70 S6K; and EGFR was conducted on tissue from metastatic sites. Nine patients were treated in the phase I portion of the study and 22 in the phase II portion. The MTD was gefitinib 250 mg on days 2-14, trastuzumab 6 mg/kg, and docetaxel 60 mg/m(2) every 21 days. For the 29 patients treated at the MTD, median PFS was 12.7 months, with complete and partial response rates of 18 and 46%, and a stable disease rate of 29%. No statistically significant correlation was found between response and expression of any biomarkers. We conclude that the combination of gefitinib, trastuzumab, and docetaxel is feasible and effective. Expression of the biomarkers examined did not predict outcome in this sample of HER-2 overexpressing metastatic breast cancer. PMID- 22042373 TI - Physical activity and quality of life of amputees in southern Brazil. AB - BACKGROUND: Physical activity is a positive component of human health. Its effects are associated with improvement in physical, psychological and social aspects of quality of life. Physical activity is therefore an important factor in the rehabilitation of amputees. OBJECTIVE: To analyse the relationship between physical activity and quality of life for amputees in southern Brazil. STUDY DESIGN: Descriptive, cross-sectional design with nonrandomized sample. METHODS: A total of 40 questionnaire instruments were distributed to subjects who met the inclusion criteria, with a response rate of 55% (22 individuals, n = 15 males, n = 7 females). Outcome measurements were obtained through the International Physical Activity Questionnaire and World Health Organization Quality of Life Bref. RESULTS: The sample was characterized by physically active adult male prosthetic users with positive quality of life, and amputation below the right knee caused by mechanical trauma related to traffic accidents with motorcycles. Significant correlations were identified between all domains of quality of life and between level of physical activity and psychological quality of life. No correlation was identified between gender and quality of life variables or physical activity levels. CONCLUSIONS: This study showed that in very active amputees of both genders, level of physical activity is not associated with quality of life except for the psychological domain. PMID- 22042374 TI - Undergraduate prosthetics and orthotics programme objectives:a baseline for international comparison and curricular development. AB - BACKGROUND: Prosthetics and orthotics is a relatively recent addition to the suite of undergraduate professional preparation programmes. There has been limited publication regarding international patterns of curriculum development, particularly concerning how objectives differ across global regions. OBJECTIVES: This paper compares current prosthetics and orthotics curricula from a range of regions and identifies both common and distinctive objectives. STUDY DESIGN: Mixed method: document analysis followed by modified Delphi process. METHODS: Documents were analysed qualitatively to compare various curricula and emergent features were evaluated by a group of expert prosthetics and orthotics instructors. RESULTS: There was substantial agreement that programmes should improve student knowledge and understanding. They should establish and extend student fabrication, communication skills and professional co-operation. However, there appeared to be regional differences in the priority given to critical thinking and clinical reasoning; integration of theory and practice and particular approaches to teaching prosthetics and orthotics. CONCLUSIONS: This study revealed substantial consensus regarding the importance of clear programme objectives dealing with student abilities, professional skills and contemporary understanding. However, this study also revealed regional differences that may well reward further investigation. PMID- 22042375 TI - In silico prediction of acyl glucuronide reactivity. AB - Drugs and drug candidates containing a carboxylic acid moiety, including many widely used non-steroidal anti-inflammatory drugs (NSAIDs) are often metabolized to form acyl glucuronides (AGs). NSAIDs such as Ibuprofen are amongst the most widely used drugs on the market, whereas similar carboxylic acid drugs such as Suprofen have been withdrawn due to adverse events. Although the link between these AG metabolites and toxicity is not proven, there is circumstantial literature evidence to suggest that more reactive acyl glucuronides may, in some cases, present a greater risk of exhibiting toxic effects. We wished therefore to rank the reactivity of potential new carboxylate-containing drug candidates, and performed kinetic studies on synthetic acyl glucuronides to benchmark our key compounds. Driven by the desire to quickly rank the reactivity of compounds without the need for lengthy synthesis of the acyl glucuronide, a correlation was established between the degradation half-life of the acyl glucuronide and the half life for the hydrolysis of the more readily available methyl ester derivative. This finding enabled a considerable broadening of chemical property space to be investigated. The need for kinetic measurements was subsequently eliminated altogether by correlating the methyl ester hydrolysis half-life with the predicted (13)C NMR chemical shift of the carbonyl carbon together with readily available steric descriptors in a PLS model. This completely in silico prediction of acyl glucuronide reactivity is applicable within the earliest stages of drug design with low cost and acceptable accuracy to guide intelligent molecular design. This reactivity data will be useful alongside the more complex additional pharmacokinetic exposure and distribution data that is generated later in the drug discovery process for assessing the overall toxicological risk of acidic drugs. PMID- 22042376 TI - Modeling the pharmacodynamics of passive membrane permeability. AB - Small molecule permeability through cellular membranes is critical to a better understanding of pharmacodynamics and the drug discovery endeavor. Such permeability may be estimated as a function of the free energy change of barrier crossing by invoking the barrier domain model, which posits that permeation is limited by passage through a single "barrier domain" and assumes diffusivity differences among compounds of similar structure are negligible. Inspired by the work of Rezai and co-workers (JACS 128:14073-14080, 2006), we estimate this free energy change as the difference in implicit solvation free energies in chloroform and water, but extend their model to include solute conformational affects. Using a set of eleven structurally diverse FDA approved compounds and a set of thirteen congeneric molecules, we show that the solvation free energies are dominated by the global minima, which allows solute conformational distributions to be effectively neglected. For the set of tested compounds, the best correlation with experiment is obtained when the implicit chloroform global minimum is used to evaluate the solvation free energy difference. PMID- 22042378 TI - Chiral squaramide-catalyzed highly diastereo- and enantioselective direct Michael addition of nitroalkanes to nitroalkenes. AB - An efficient highly diastereo- and enantioselective direct Michael addition of nitroalkanes to nitroalkenes catalyzed by chiral squaramide catalyst has been developed. This organocatalytic reaction with a low catalyst loading (2 mol%) proceeded well to afford synthetically useful 1,3-dinitro compounds in high yields with high diastereoselectivities (up to 95 : 5 dr) and excellent enantioselectivities (up to 97% ee). PMID- 22042377 TI - Conformational studies of immunodominant myelin basic protein 1-11 analogues using NMR and molecular modeling. AB - Tauwo dimensional nuclear magnetic resonance studies complimented by molecular dynamics simulations were conducted to investigate the conformation of the immunodominant epitope of acetylated myelin basic protein residues 1-11 (Ac-MBP(1 11)) and its altered peptide ligands, mutated at position 4 to an alanine (Ac MBP(1-11)[4A]) or a tyrosine residue (Ac-MBP(1-11)[4Y]). Conformational analysis of the three analogues indicated that they adopt an extended conformation in DMSO solution as no long distance NOE connectivities were observed and seem to have a similar conformation when bound to the active site of the major histocompatibility complex (MHC II). The interaction of each peptide with MHC class II I-A(u) was further investigated in order to explore the molecular mechanism of experimental autoimmune encephalomyelitis induction/inhibition in mice. The present findings indicate that the Gln(3) residue, which serves as a T cell receptor (TCR) contact site in the TCR/peptide/I-A(u) complex, has a different orientation in the mutated analogues especially in the Ac-MBP(1-11)[4A] peptide. In particular the side chain of Gln(3) is not solvent exposed as for the native Ac-MBP(1-11) and it is not available for interaction with the TCR. PMID- 22042379 TI - Recognition memory without awareness during transient global amnesia. PMID- 22042381 TI - Effect of bending rigidity in a dynamic model of a polyurethane prosthetic mitral valve. AB - We investigate the behaviour of a dynamic fluid-structure interaction model of a chorded polyurethane mitral valve prosthesis, focusing on the effects on valve dynamics of including descriptions of the bending stiffnesses of the valve leaflets and artificial chordae tendineae. Each of the chordae is attached at one end to the valve annulus and at the other to one of two chordal attachment points. These attachment points correspond to the positions where the chords of the real prosthesis would attach to the left-ventricular wall, although in the present study, these attachment points are kept fixed in space to facilitate comparison between our simulations and earlier results obtained from an experimental test rig. In our simulations, a time-dependent pressure difference derived from experimental measurements drives flow through the model valve during diastole and provides a realistic pressure load during systole. In previous modelling studies of this valve prosthesis, the valve presents an unrealistically large orifice at beginning of diastole and does not close completely at the end of diastole. We show that including a description of the chordal bending stiffness enables the model valve to close properly at the end of the diastolic phase of the cardiac cycle. Valve over-opening is eliminated only by incorporating a description of the bending stiffnesses of the valve leaflets into the model. Thus, bending stiffness plays a significant role in the dynamic behaviour of the polyurethane mitral valve prosthesis. PMID- 22042382 TI - Bioabsorbable Gore BIO-A plug and patch hernia repair in young adults. PMID- 22042383 TI - Prosthetic repair of umbilical hernias in adults with local anesthesia in a day case setting: a comprehensive report from a specialized hernia center. AB - BACKGROUND: Umbilical hernia is a common surgical problem. However, there seems to be a certain discrepancy between its importance and the attention it has received in the literature to date. This prospective study aimed to report a detailed analysis of prosthetic umbilical hernia repairs with local anesthesia in a day-case setting. METHODS: It was planned to enroll 100 consecutive patients who underwent an elective umbilical hernia repair with local anesthesia. Patients who required general anesthesia and simultaneous hernia repairs were excluded. The procedure including local anesthesia and intravenous sedation was explained to the patients in detail by the operating surgeons and the anesthesiologist. The following parameters were strictly recorded: gender, age, body mass index (BMI), concomitant diseases, history of hernia (primary/recurrent), size of fascial defect, duration of operation, level of intravenous sedation (light/moderate), discharge time, and complications. RESULTS: There were 54 male and 46 female patients. The mean age was 48.6 years (24-78 years). Four patients were older than 70 years of age. Forty-one patients had 84 concomitant diseases. Eleven patients had a recurrent hernia. Female patients more frequently presented with a recurrent hernia than male patients (19.6 vs. 3.7%, P = 0.009). A standard polypropylene mesh was used in the onlay position in 91 cases. In nine cases, a light mesh was placed in the preperitoneal space. A closed vacuum drain was left in situ in 37 cases. Light sedation was set in 86 cases, whereas 12 patients received a moderate sedation. Monitored anesthesia care was used in two cases. When moderate sedation was needed, a concurrent increase in lidocaine dose and total volume was recorded. There was a positive correlation between increased lidocaine use and high midazolam dose and additional propofol requirement. The mean total local anesthetic volume was 33 ml (10-63 ml). Lidocaine doses displayed a large range between the cases (70-600 mg). The mean lidocaine dose was 263.3 mg (standard deviation [SD]: 103.4). No bupivacaine was given in 19 cases, whereas the mean bupivacaine dose was 35.1 mg (0-100 mg) in 81 cases. The mean duration in the operation room was 69 min (25-150 min). It was significantly longer for recurrent hernias than primary ones (95 vs. 65 min; P = 0.0001). Higher total volume and higher lidocaine doses were required for the repair of recurrent hernias. In addition, it was observed that the longer the operation time, then the longer the lidocaine dose and the higher the total volume of local anesthetic agents. The patient satisfaction rate was 97%. The mean discharge time was 122 +/- 58 min (45-420 min). Sixty-seven patients were sent home within 2 h. Early wound problems were observed in 11 patients. Small seromas and hematomas developed in six cases, and dissolved without drainage. Three superficial surgical site infections diagnosed by erythema and enduration were recorded without obvious suppuration. No recurrence was recorded after a mean follow-up of 17 months (5-41 months). One patient complained of pain at the lower edge of a standard polypropylene mesh at the third postoperative month. CONCLUSIONS: The repair of umbilical hernias with local anesthesia in a day-case setting is a good option, with low infection and recurrence rates. Most patients can be discharged early as planned. Separate doses and total volume of local anesthetic agents needed for umbilical hernia repair are clearly higher than those used in inguinal hernia repair. Patients with higher BMI, recurrent hernia, and defects larger than 3 cm may require higher local analgesic doses. The patient satisfaction is very good when the patients are provided with detailed information about day surgery and local anesthesia. PMID- 22042384 TI - Beck Hopelessness Scale: exploring its dimensionality in patients with schizophrenia. AB - Hopelessness is a pre-eminent risk factor for suicide and non-fatal self-harm. Although the Beck Hopelessness Scale is often used for schizophrenia, its factor structure has been given relatively little consideration in this context. This study aimed to examine the reliability and validity of the Taiwanese version of the Beck Hopelessness Scale (BHS-T) in a chronic schizophrenia out-patient sample. One hundred and two (102) outpatients were evaluated using the translated Taiwanese version of the BHS (BHS-T), as well as several Beck-related symptom rating scales and the Positive and Negative Syndrome Scale (PANSS) for psycho pathology. The patients were also evaluated for suicidal intent using the critical items of the Scale for Suicide Ideation (SSI) and suicide attempts. The psychometric properties of the BHS-T were also evaluated, including construct validity, internal consistency, test-retest reliability, convergence, and discriminative validity. The BHS-T showed good overall reliability and stability over time. This translated scale comprised a two-factor solution corresponding negative expectation and loss of motivation dimensions. Differences in mean hopelessness scores between participants with and without suicidal intent were significant. The results also indicated that, among individuals with schizophrenia, "negative expectation in the future" is more closely linked to suicide intent than "loss of motivation for the future". The BHS-T is a reliable and valid instrument for measuring the multi-dimensionality of hopelessness and may complement clinical suicidal risk assessments in individuals with schizophrenia. PMID- 22042386 TI - The new irrationalism in weaning. PMID- 22042385 TI - Prenatal excess glucocorticoid exposure and adult affective disorders: a role for serotonergic and catecholamine pathways. AB - Fetal glucocorticoid exposure is a key mechanism proposed to underlie prenatal 'programming' of adult affective behaviours such as depression and anxiety. Indeed, the glucocorticoid metabolising enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which is highly expressed in the placenta and the developing fetus, acts as a protective barrier from the high maternal glucocorticoids which may alter developmental trajectories. The programmed changes resulting from maternal stress or bypass or from the inhibition of 11beta HSD2 are frequently associated with alterations in the hypothalamic-pituitary adrenal (HPA) axis. Hence, circulating glucocorticoid levels are increased either basally or in response to stress accompanied by CNS region-specific modulations in the expression of both corticosteroid receptors (mineralocorticoid and glucocorticoid receptors). Furthermore, early-life glucocorticoid exposure also affects serotonergic and catecholamine pathways within the brain, with changes in both associated neurotransmitters and receptors. Indeed, global removal of 11beta HSD2, an enzyme that inactivates glucocorticoids, increases anxiety- and depressive-like behaviour in mice; however, in this case the phenotype is not accompanied by overt perturbation in the HPA axis but, intriguingly, alterations in serotonergic and catecholamine pathways are maintained in this programming model. This review addresses one of the potential adverse effects of glucocorticoid overexposure in utero, i.e. increased incidence of affective behaviours, and the mechanisms underlying these behaviours including alteration of the HPA axis and serotonergic and catecholamine pathways. PMID- 22042387 TI - [Six-minute walk test: necessary in order to understand patient limitations]. PMID- 22042388 TI - Six-minute walk test: reference values for healthy adults in Brazil. AB - OBJECTIVE: To develop regression equations for six-minute walk distance (6MWD) in healthy adults (20-80 years of age) in Brazil. METHODS: We included 132 volunteers (66 males) without respiratory disease, cardiac disease, or comorbidities that affect ambulation. The volunteers completed three six-minute walk tests. Prior to and at the end of each test, we obtained SpO2 and maximal HR, as well as the Borg scale scores for sensation of dyspnea and lower limb fatigue. The data included in the final analysis were derived from the test with the greatest 6MWD. RESULTS: The mean 6MWD values were 566 +/- 87 m and 538 +/- 95 m in males and females, respectively (p = 0.08). The 6MWD was greater in taller individuals and decreased in parallel with increases in age or body index mass (BMI). The best adjusted model was the quadratic model. We derived the following equation (valid for both genders): 6MWD = 511 + stature2 (cm) * 0.0066 - age2 * 0.030 - BMI2 * 0.068. This equation explained 55% of the variance in 6MWD. CONCLUSIONS: Reference values explaining a high proportion of the variance were derived by a quadratic regression model in healthy adults (of a wide range of ages) in Brazil. PMID- 22042389 TI - Acute asthma management in children: knowledge of the topic among health professionals at teaching hospitals in the city of Recife, Brazil. AB - OBJECTIVE: Knowledge of acute asthma management in children is a subject that has rarely been explored. The objective of this study was to assess the level of such knowledge among health professionals in the city of Recife, Brazil. METHODS: This was a cross-sectional survey involving 27 pediatricians and 7 nurses, all with at least two years of professional experience, at two large pediatric teaching hospitals in Recife. The participants completed a self-administered multiple choice questionnaire. RESULTS: The pediatricians and nurses all possessed insufficient knowledge regarding the use of metered dose inhalers, nebulization, and types/doses of medications, as well as techniques for decontamination and disinfection of the equipment. CONCLUSIONS: Insufficient knowledge of acute asthma management in children can lead to less effective treatment in hospitals such as those evaluated here. Educational programs should be developed in order to minimize this problem. PMID- 22042390 TI - An experimental rat model of ex vivo lung perfusion for the assessment of lungs after prostacyclin administration: inhaled versus parenteral routes. AB - OBJECTIVE: To present a model of prostaglandin I2 (PGI2) administration (inhaled vs. parenteral) and to assess the functional performance of the lungs in an ex vivo lung perfusion system. METHODS: Forty Wistar rats were anesthetized and placed on mechanical ventilation followed by median sterno-laparotomy and anticoagulation. The main pulmonary artery was cannulated. All animals were maintained on mechanical ventilation and were randomized into four groups (10 rats/group): inhaled saline (IS); parenteral saline (PS); inhaled PGI2 (IPGI2); and parenteral PGI2 (PPGI2). The dose of PGI2 used in the IPGI2 and PPGI2 groups was 20 and 10 ug/kg, respectively. The heart-lung blocks were submitted to antegrade perfusion with a low potassium and dextran solution via the pulmonary artery, followed by en bloc extraction and storage at 4oC for 6 h. The heart-lung blocks were then ventilated and perfused in an ex vivo lung perfusion system for 50 min. Respiratory mechanics, hemodynamics, and gas exchange were assessed. RESULTS: Mean pulmonary artery pressure following nebulization decreased in all groups (p < 0.001), with no significant differences among the groups. During the ex vivo perfusion, respiratory mechanics did not differ among the groups, although relative oxygenation capacity decreased significantly in the IS and PS groups (p = 0.04), whereas mean pulmonary artery pressure increased significantly in the IS group. CONCLUSIONS: The experimental model of inhaled PGI2 administration during lung extraction is feasible and reliable. During reperfusion, hemodynamics and gas exchange trended toward better performance with the use of PGI2 than that with the use of saline. PMID- 22042391 TI - Hematopoietic stem cell transplantation: pulmonary function tests and post transplant mortality. AB - OBJECTIVE: To determine whether the results of pulmonary function tests carried out in patients subsequently submitted to hematopoietic stem cell transplantation (HSCT) are associated with post-HSCT mortality. METHODS: This was a prospective study involving patients older than 15 years of age who were submitted to allogenic HSCT between January of 2007 and March of 2008 at the Hospital das Clinicas da Universidade Federal de Minas Gerais, located in the city of Belo Horizonte, Brazil. Prior to HSCT, all of the patients underwent spirometry, determination of lung volumes, and determination of DLCO. Those same tests were repeated six months, one year, and two years after HSCT. Kaplan-Meier curves and two-tailed log-rank tests were used for survival analysis. The relative risk (RR) and 95% CI were calculated using the Cox proportional hazards model. The Cox regression model was used in the multivariate analysis. RESULTS: The pre-HSCT pulmonary function results were normal in 40 (74.1%) of the 54 patients evaluated, 19 (35.2%) of whom died within the first 100 days after HSCT. By the end of the two-year follow-up period, 23 patients (42.6%) had died, the most common causes of death being septicemia, observed in 11 (47.8%), and septicemia related respiratory insufficiency, observed in 10 (43.4%). The only variables significantly associated with post-HSCT mortality were alterations in spirometry results prior to HSCT (RR = 3.2; p = 0.016) and unrelated donor (RR = 9.0; p < 0.001). CONCLUSIONS: Performing spirometry prior to HSCT provides baseline values for future comparisons. Although alterations in spirometry results reveal a higher risk of post-HSCT mortality, such alterations do not contraindicate the procedure. PMID- 22042392 TI - Reference equations for the performance of healthy adults on field walking tests. AB - OBJECTIVE: To develop regression equations for predicting six-minute and incremental shuttle walk distances (6MWD and ISWD, respectively), based on demographic characteristics, anthropometric variables, and grip strength. METHODS: We evaluated 6MWD and ISWD in 98 healthy adults. Height, weight, and grip strength were also assessed. Using data from 90 of the participants (40 males; 60 +/- 9 years of age), we devised linear equations adjusted for age, gender, height, and weight, and we developed alternate models that included grip strength. We prospectively applied the equations in the 8 remaining participants (4 males; 59 +/- 10 years), who had been randomly separated from the initial sample. RESULTS: Age, gender, height, and weight collectively explained 54.5% and 64.9% of the variance in 6MWD and ISWD, respectively, whereas age, height, weight, and grip strength collectively explained 54.4% and 69.0% of the respective variances. There was no significant difference between the measured and predicted 6MWD using equations with and without grip strength (14 +/- 57 vs. 13 +/- 67 m). Similar results were observed for ISWD (25 +/- 104 vs. 25 +/- 93 m). CONCLUSIONS: Grip strength is a determinant of ISWD and 6MWD; however, it could not improve the power of equations adjusted by demographic and anthropometric variables. The validity of our models including grip strength should be further evaluated in patients with skeletal muscle dysfunction. PMID- 22042393 TI - Spirometric reference values for healthy adults in the Mazandaran province of Iran. AB - OBJECTIVE: One of the major issues in the use of spirometry is the evaluation of the values obtained in comparison with standardized reference values. Such reference values should be determined by studying populations similar to the population in which they are intended to be used. Considering the anthropometric differences among races and the effect of regional issues, such as climate and air quality, it is recommended that these standards be set and used regionally. The objective of this study was to measure the spirometric values in residents of the Mazandaran province in Iran, as well as to determine which standardized reference values most closely correlate with the values obtained and to devise predictive equations for the target population. METHODS: This was a cross sectional study of 1,499 volunteers, from whom demographic and anthropometric data were collected. After having been instructed in the correct procedure, each volunteer underwent spirometry. From each volunteer, we obtained three spirometry curves that met the acceptability criteria established by the American Thoracic Society. The test with the highest values of FEV1 and FVC was employed in the analysis. RESULTS: We observed significant correlations between the measured values and the reference values, for both genders. The strongest correlations were with the European Respiratory Society reference values and with the 18-20 year age bracket. The predictive equations devised were based on the regression coefficients obtained and the demographic data collected. CONCLUSIONS: Our results show that the European Respiratory Society standard is the most appropriate standard for use in the population studied. PMID- 22042394 TI - Influenza A (H1N1)-associated pneumonia. AB - OBJECTIVE: To describe the characteristics of patients with influenza A (H1N1) associated pneumonia treated at two hospitals in the region of Liguria, Italy, as well as to describe their treatment and outcomes. METHODS: This was a prospective observational study including all patients older than 16 years of age with a confirmed diagnosis of influenza A (H1N1) who were admitted to Villa Scassi Hospital, in the city of Genoa, Italy, or to the Sestri Levante General Hospital, in the city of Sestri Levante, Italy, between September of 2009 and January of 2010. The primary outcome measure was mortality within 60 days after diagnosis. Secondary outcome measures were the need for mechanical ventilation and the length of hospital stay. RESULTS: Of the 40 patients with a confirmed diagnosis of influenza A (H1N1), 27 presented pneumonia during the study period. The mean age of the 27 patients was 42.8 +/- 14.8 years, and the mean length of hospital stay was 11.6 +/- 8.2 days. Of the 27 patients, 20 had respiratory failure, 4 underwent invasive mechanical ventilation, and 5 underwent noninvasive ventilation. One patient had comorbidities, developed multiple organ failure, and died. CONCLUSIONS: During the influenza A (H1N1) pandemic, the associated mortality rate was lower in Italy than in other countries, and cases reported in the country typically had a milder course than did those reported elsewhere. Nevertheless, 9 of our cases (33%) rapidly evolved to respiratory failure, requiring mechanical ventilation. PMID- 22042395 TI - Restriction enzyme analysis of the hsp65 gene in clinical isolates from patients suspected of having pulmonary tuberculosis in Teresina, Brazil. AB - OBJECTIVE: To identify mycobacterial species in the sputum of patients suspected of having pulmonary tuberculosis and to determine the impact that the acquisition of this knowledge has on the therapeutic approach. METHODS: We evaluated 106 patients suspected of having pulmonary tuberculosis and referred to the pulmonology department of a public hospital in the city of Teresina, Brazil. Morning sputum specimens were evaluated for the presence of mycobacteria by sputum smear microscopy and culture. We used PCR and restriction enzyme analysis of the hsp65 gene (PRA-hsp65) to identify the strains of mycobacteria isolated in culture. RESULTS: A total of 206 sputum samples were analyzed. Patient ages ranged from 15 to 87 years, and 67% were male. There was cough in 100% of the cases. The predominant radiographic pattern was moderate disease, observed in 70%. Smear positivity was 76%, and isolation in culture occurred in 91% of the cultures. Traditional tests identified nontuberculous mycobacteria (NTM) in 9% of the isolates. The PRA-hsp65 method confirmed these data, showing seven band patterns that were able to identify the isolated species of NTM: Mycobacterium kansasii; M. abscessus 1; M. abscessus 2; M. smegmatis; M. flavescens 1; M. gordonae 5; and M. gordonae 7. All of the patients with NTM were over 60 years of age, and bronchiectasis was seen in 88% of the X-rays. There were two cases of reinfection, initially attributed to M. abscessus and M. kansasii. CONCLUSIONS: In immunocompetent patients, NTM can infect the lungs. It is important to identify the specific NTM in order to establish the correct diagnosis and choose the most appropriate therapeutic regimen. The PRA-hsp65 method is useful in identifying NTM species and can be implemented in molecular biology laboratories that do not specialize in the identification of mycobacteria. PMID- 22042396 TI - Active tuberculosis among health care workers in Portugal. AB - OBJECTIVE: To determine the incidence of active tuberculosis (TB) in a cohort of health care workers (HCWs). METHODS: Descriptive study of active TB cases identified in an occupational health screening of 6,112 HCWs between 2005 and 2010. Cases of active TB were defined as those in which Mycobacterium tuberculosis was identified by direct microscopy or culture; those in which there were symptoms or clinical signs of TB and necrotizing granuloma, as detected by histology; and those in which the radiological findings were consistent with active TB. RESULTS: Among the 6,112 HCWs evaluated, we identified 62 cases of active TB: pulmonary TB (n = 43); pleural TB (n = 15); lymph node TB (n = 2); pericardial TB (n = 1); and cutaneous TB (n = 1). Seven HCWs were asymptomatic at the time of diagnosis. Of the 62 cases of active TB, 48 developed within the first 10 years of occupational exposure in the workplace, 36 of those occurring within the first 5 years. Physicians and nurses accounted for the highest numbers of cases (22 and 21, respectively). CONCLUSIONS: In HCWs employed in Portugal, the TB burden is high. Physicians and nurses are the HCWs who are at the highest risk of developing active TB. We found the risk of developing this disease to be highest in the first years of exposure, as has been reported in previous studies. In high-incidence countries, TB screening of HCWs is important for controlling the transmission of this disease. PMID- 22042397 TI - Tuberculin skin test: operational research in the state of Mato Grosso do Sul, Brazil. AB - OBJECTIVE: To investigate operational aspects of tuberculin skin test (TST) use in tuberculosis control programs and at specialized Brazilian National Sexually Transmitted Diseases/AIDS and Viral Hepatitis Program health care clinics in priority municipalities for tuberculosis control in the state of Mato Grosso do Sul, Brazil. METHODS: This was a descriptive, cross-sectional, epidemiological survey. Data on qualifications/training of professionals administering TSTs, timing of the TST, procedures in cases of loss to follow-up (reading), material availability, and material storage were collected through interviews and technical visits. For the 2008-2009 period, we determined the numbers of screenings in vulnerable populations, of TSTs performed, and of patients treated for latent tuberculosis. RESULTS: We interviewed 12 program managers in six municipalities. Some programs/clinics did not perform TSTs. Nursing teams administered the TSTs, results were read by non-specialists, and specialization/refresher courses were scarce. The PPD RT23 was stored in 5-mL flasks under appropriate conditions. Insulin syringes were commonly used. Testing was available during business hours, three times a week. In cases of loss to follow-up, telephone calls or home visits were made. Of the 2,305 TSTs evaluated, 1,053 (46%) were performed in indigenous populations; 831 (36%) were screenings in prisons, performed for training; and only 421 (18%) involved contacts of tuberculosis patients or vulnerable populations. Four vulnerable patients and 126 indigenous subjects were treated for latent tuberculosis. CONCLUSIONS: These priority municipalities showed operational difficulties regarding human resources, materials, and data records. PMID- 22042398 TI - Occurrence of influenza among patients hospitalized for suspicion of influenza A (H1N1) infection in 2010 at a sentinel hospital in Sao Paulo, Brazil. AB - In 2010, 96 patients suspected of being infected with the influenza A (H1N1) virus were hospitalized at the Hospital Sao Paulo, located in the city of Sao Paulo, Brazil. Of those 96 patients, 4 (4.2%) were found to be infected with influenza A virus-3 with influenza A (H1N1) and 1 with seasonal influenza A-and 2 patients (2.1%) were found to be infected with influenza B virus. Most (63.5%) of the suspected cases occurred in children, as did half of the positive cases. The second wave of influenza A (H1N1) infection was weaker in Sao Paulo. The decrease in the number of hospitalizations for H1N1 infection in 2010 might be attributable to vaccination. PMID- 22042399 TI - Negative expiratory pressure test: a new, simple method to identify patients at risk for obstructive sleep apnea. AB - The objective of this article was to describe a new method for assessing expiratory flow limitation during spontaneous breathing, using the negative expiratory pressure test to identify patients at risk for obstructive sleep apnea. Upper airway collapsibility is evaluated by measuring decreases in flow and in expired volume in the first 0.2 seconds after negative expiratory pressure application at 10 cmH2O. The negative expiratory pressure test is easily applied and could be adopted for the evaluation of expiratory flow limitation caused by upper airway obstruction in patients with obstructive sleep apnea. PMID- 22042400 TI - Identification of Mycobacterium bovis among mycobacterial isolates from human clinical specimens at a university hospital in Rio de Janeiro, Brazil. AB - In 2005 and 2006, 8,121 clinical specimens submitted to the Mycobacteriology Laboratory of the Clementino Fraga Filho University Hospital/Thoracic Diseases Institute, in the city of Rio de Janeiro, Brazil, were inoculated on Lowenstein Jensen medium containing glycerol and pyruvate. There were 79 mycobacteria isolates that presented growth only on pyruvate-containing medium, and those isolates were selected for the presumptive identification of Mycobacterium bovis. The selected isolates were screened with biochemical tests, PCR amplification (with the specific primers Rv0577 and Rv1510), and pyrazinamide susceptibility tests. All of the strains isolated showed specific phenotypical and genotypical patterns characteristic of M. tuberculosis, and no M. bovis strains were detected. PMID- 22042401 TI - Predictive parameters for weaning from mechanical ventilation. AB - The use of predictive parameters for weaning from mechanical ventilation is a rather polemic topic, and the results of studies on this topic are divergent. Regardless of the use of these predictive parameters, the spontaneous breathing trial (SBT) is recommended. The objective of the present study was to review the utility of predictive parameters for weaning in adults. To that end, we searched the Medline, LILACS, and PubMed databases in order to review articles published between 1991 and 2009, in English or in Portuguese, using the following search terms: weaning/desmame, extubation/extubacao, and weaning indexes/indices de desmame. The use of clinical impression is an inexact means of predicting weaning outcomes. The most widely used weaning parameter is the RR/tidal volume (V T) ratio, although this parameter presents heterogeneous results in terms of accuracy. Other relevant parameters are MIP, airway occlusion pressure (P0.1), the P0.1/MIP ratio, RR, V T, minute volume, and the index based on compliance, RR, oxygenation, and MIP. An index created in Brazil, the integrative weaning index, has shown high accuracy. Although recommended, the SBT is inaccurate, approximately 15% of extubation failures going unidentified in SBTs. The main limitations of the weaning indexes are related to their use in specific populations, the cut-off points selected, and variations in the types of measurement. Since the SBT and the clinical impression are not 100% accurate, the weaning parameters can be useful, especially in situations in which the decision as to weaning is difficult. PMID- 22042402 TI - Gastroesophageal reflux disease and airway hyperresponsiveness: concomitance beyond the realm of chance? AB - Gastroesophageal reflux disease and asthma are both quite common the world over, and they can coexist. However, the nature of the relationship between these two diseases remains unclear. In this study, we review controversial aspects of the relationships among asthma, airway hyperresponsiveness, and gastroesophageal reflux disease in adults and in children. PMID- 22042403 TI - Pulmonary actinomycosis as a pseudotumor: a rare presentation. AB - Some lung diseases are true diagnostic challenges due to their various clinical presentations. Actinomycosis is one such disease, potentially affecting various organs and systems. We report the case of a patient with pulmonary actinomycosis as a pseudotumor, which is usually only diagnosed by thoracotomy or thoracoscopy. PMID- 22042404 TI - Robotic thymectomy for myasthenia gravis. PMID- 22042405 TI - Diaphragmatic pacing: unusual indication with successful application. PMID- 22042406 TI - Nonfunctional middle mediastinal paraganglioma: diagnostic and surgical management. PMID- 22042407 TI - A framework for responding to coral disease outbreaks that facilitates adaptive management. AB - Predicted increases in coral disease outbreaks associated with climate change have implications for coral reef ecosystems and the people and industries that depend on them. It is critical that coral reef managers understand these implications and have the ability to assess and reduce risk, detect and contain outbreaks, and monitor and minimise impacts. Here, we present a coral disease response framework that has four core components: (1) an early warning system, (2) a tiered impact assessment program, (3) scaled management actions and (4) a communication plan. The early warning system combines predictive tools that monitor the risk of outbreaks of temperature-dependent coral diseases with in situ observations provided by a network of observers who regularly report on coral health and reef state. Verified reports of an increase in disease prevalence trigger a tiered response of more detailed impact assessment, targeted research and/or management actions. The response is scaled to the risk posed by the outbreak, which is a function of the severity and spatial extent of the impacts. We review potential management actions to mitigate coral disease impacts and facilitate recovery, considering emerging strategies unique to coral disease and more established strategies to support reef resilience. We also describe approaches to communicating about coral disease outbreaks that will address common misperceptions and raise awareness of the coral disease threat. By adopting this framework, managers and researchers can establish a community of practice and can develop response plans for the management of coral disease outbreaks based on local needs. The collaborations between managers and researchers we suggest will enable adaptive management of disease impacts following evaluating the cost-effectiveness of emerging response actions and incrementally improving our understanding of outbreak causation. PMID- 22042408 TI - Effects of river restoration on riparian biodiversity in secondary channels of the Pite River, Sweden. AB - Between 1850 and 1970, rivers throughout Sweden were channelized to facilitate timber floating. Floatway structures were installed to streamline banks and disconnect flow to secondary channels, resulting in simplified channel morphologies and more homogenous flow regimes. In recent years, local authorities have begun to restore channelized rivers. In this study, we examined the effects of restoration on riparian plant communities at previously disconnected secondary channels of the Pite River. We detected no increase in riparian diversity at restored sites relative to unrestored (i.e., disconnected) sites, but we did observe significant differences in species composition of both vascular plant and bryophyte communities. Disconnected sites featured greater zonation, with mesic hydric floodplain species represented in plots closest to the stream and mesic xeric upland species represented in plots farthest from the stream. In contrast, restored sites were most strongly represented by upland species at all distances relative to the stream. These patterns likely result from the increased water levels in reconnected channels where, prior to restoration, upland plants had expanded toward the stream. Nonetheless, the restored fluvial regime has not brought about the development of characteristic flood-adapted plant communities, probably due to the short time interval (ca. 5 years) since restoration. Previous studies have demonstrated relatively quick responses to similar restoration in single-channel tributaries, but secondary channels may respond differently due to the more buffered hydrologic regimes typically seen in anabranching systems. These findings illustrate how restoration outcomes can vary according to hydrologic, climatic and ecological factors, reinforcing the need for site specific restoration strategies. PMID- 22042409 TI - Do postfire mulching treatments affect plant community recovery in California coastal sage scrub lands? AB - In recent years, the use of postfire mulch treatments to stabilize slopes and reduce soil erosion in shrubland ecosystems has increased; however, the potential effects on plant recovery have not been examined. To evaluate the effects of mulching treatments on postfire plant recovery in southern California coastal sage scrub, we conducted a field experiment with three experimental treatments, consisting of two hydromulch products and an erosion control blanket, plus a control treatment. The area burned in 2007, and treatments were applied to six plot blocks before the 2008 growing season. Treatment effects on plant community recovery were analyzed with a mixed effects ANOVA analysis using a univariate repeated measures approach. Absolute plant cover increased from 13 to 90% by the end of the second growing season, and the mean relative cover of exotic species was 32%. The two hydromulch treatments had no effect on any plant community recovery response variable measured. For the erosion control blanket treatment, the amount of bare ground cover at the end of the second growing season was significantly lower (P = 0.01), and greater shrub height was observed (P < 0.01). We conclude that postfire mulch treatments did not provide either a major benefit or negative impact to coastal sage scrub recovery on the study area. PMID- 22042411 TI - The wee hours. PMID- 22042410 TI - Isozyme-specific effects of protein kinase C in pain modulation. AB - BACKGROUND: Protein kinase C (PKC) is a family of serine/threonine kinases that contains more than 10 isozymes. Evidence suggests that PKC may play important roles in pain modulation, but the isozyme-specific effects of PKC on different aspects of pain modulation are not fully understood. We hypothesize that different PKC isozymes play different roles in different aspects of pain modulation. METHODS: The nociceptive behaviors of mice with deletion of PKCalpha, beta, gamma, or delta in multiple pain models were compared with their respective wild-type littermates. Also, morphine analgesia and the development of morphine tolerance in mice with deletion of PKCgamma were compared with their respective wild-type littermates. RESULTS: Thermal hyperalgesia induced by complete Freund's adjuvant injection was significantly attenuated by the deletion of PKCbeta, gamma, or delta, but not PKCalpha. Deletion of PKCgamma significantly attenuated neuropathic mechanical allodynia induced by spared nerve injury, whereas deletion of PKCalpha enhanced this allodynia. Baseline thermal and mechanical sensitivity, nociceptive behaviors induced by formalin, mechanical allodynia induced by complete Freund's adjuvant injection, were not altered by deletion of PKCalpha, beta, gamma, or delta. Finally, morphine analgesia and the development of morphine tolerance were not altered in PKCgamma-deficient mice. CONCLUSIONS: PKC has isozyme-specific effects in pain modulation. PMID- 22042412 TI - Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. AB - BACKGROUND: As a potent anticoagulant agent, rivaroxaban exposes a risk of bleeding. An effective way to reverse its effects is needed. Objectives were to study efficacy and safety of recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of an overdose of rivaroxaban in a rabbit model of bleeding and thrombosis. METHODS: First, a dose-ranging study assessed the minimal rivaroxaban dose that increased bleeding. Then, 48 anesthetized and ventilated rabbits were randomized into four groups: control (saline), rivaroxaban (rivaroxaban and saline), rFVIIa (rivaroxaban and rFVIIa), and PCC (rivaroxaban and PCC). The Folts model was applied: a stenosis and an injury were carried out on the carotid artery, inducing thrombosis, detected as cyclic flow reductions, which were recorded over 20 min. Then the following were measured: ear immersion bleeding time, clotting times, anti-Xa activity, thrombelastometric parameters, and thrombin generation test. Ultimately, a hepatosplenic section was performed and the total amount of blood loss after 15 min was evaluated as primary endpoint. RESULTS: Rivaroxaban increased blood loss (17 g [8-32] vs. 7 g [5-18] for control (median [range]), P = 0.0004), ear bleeding time, clotting times, thrombelastographic clotting time, and decreased thrombin generation. In contrast, rFVIIa decreased ear bleeding time (92 s [65-115] vs. 140 s [75-190], P < 0.02), but without efficacy on blood loss. PCC and rFVIIa decreased activated partial thromboplastin time as well as thrombelastographic clotting time. Regarding safety, neither rFVIIa nor PCC increased cyclic flow reductions. CONCLUSION: rFVIIa and PCC partially improved laboratory parameters, but did not reverse rivaroxaban induced-bleeding. PMID- 22042413 TI - [What is new in prostate imaging?]. PMID- 22042414 TI - Towards a low-spin configuration in extended metal atom chains. Theoretical study of trimetallic systems with 22 metal electrons. AB - Different electronic configurations of a series of trinuclear heterometallic chains with 22 metallic electrons, MM'M(dpa)(4)X(2) (M = Co, Rh; M' = Ni, Pd; X = Cl, NCS), have been modelled in search of new systems with novel electrical properties. For this purpose, we explore the possibility of obtaining low-spin (extensively closed-shell) states by introducing chemical changes to the reference compound CoPdCo(dpa)(4)Cl(2) (1), isoelectronic to the herein studied systems, but possessing magnetically coupled localized electrons. The discussion is based on the orbital energies obtained by the DFT methodology. Among the systems herein analysed, CoNiCo(dpa)(4)(NCS)(2) has only two unpaired electrons vs. six in the case of 1, its closed-shell configuration appearing at high energies. For Rh(2)M-based chains, changes go a step further and the RhPdRh(dpa)(4)Cl(2) and RhPdRh(dpa)(4)(NCS)(2) molecules present a closed-shell ground state in close competition with the broken symmetry solution with S = 1/2 on each Rh(II). One-electron reduction of the latter compounds has been computed with marked structural changes. Our calculations show that the two lowest 23 electron states are separated by 7-8 kcal mol(-1) in favour of the state with an unpaired localized electron on the delta(Pd-N)* orbital instead of the delocalized one (sigma(nb))(2)(sigma*)(1). PMID- 22042415 TI - [Are proton pump inhibitors effective in asthmatics with gastroesophageal reflux disease?]. AB - Effects of proton pump inhibitors in asthmatics with gastroesophageal reflux disease (Korean J Gastroenterol 2011;58:178-183). PMID- 22042416 TI - [Inflammatory bowel disease and lymphoproliferative disorders]. AB - The risk of lymphoproliferative disorders (LPDs) has been reported to be increased in autoimmune diseases and chronic inflammatory diseases. Similar with other chronic inflammatory diseases such as rheumatoid arthritis, there is a concern about the risk of LPDs in patients with inflammatory bowel disease (IBD). Generally, in IBD patients, the risk of LPDs appears to be similar with or very slightly higher, compared to the general population. The association of therapeutic agents with the risk of LPDs is difficult to evaluate due to multiple other potentially involved factors and co-treatment with other agents. To date, data show that thiopurine is associated with a moderately increased risk of LPDs in patients with IBD. Evidence regarding the risk of LPDs in IBD patients using methotrexate is not sufficient, but the risk of LPDs seems low. The responsibility of anti-TNF-a agents on the risk of LPDs is difficult to determine, because most of IBD patients receiving anti-TNF-a agents are co treated with thiopurines. Attention should be given to the high risk of hepatosplenic T-cell lymphoma in young male patients treated with anti-TNF-a agents together with thiopurines. The risk and benefit of immunosuppressive therapy for IBD should be carefully evaluated and individualized considering the risk of LPDs. PMID- 22042417 TI - [Effects of proton pump inhibitors in asthmatics with gastroesophageal reflux disease]. AB - BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is common in asthma patients. Proton pump inhibitor (PPI) therapy improves symptoms of asthma in some patients. The objective of this study was to investigate endoscopic findings of GERD in asthma patients and to assess the effect of gastric acid suppression with the PPIs on symptom improvement and pulmonary function. METHODS: From 105 consecutive patients with GERD symptoms during follow up for asthma, 45 patients were enrolled. Patients enrolled to this study were asked about GERD symptoms before and after treating with PPI. Endoscopic findings were described according to Los Angeles classification. The improvement of asthma symptoms and follow-up pulmonary function test were investigated after administration of PPIs. RESULTS: Esophageal symptoms such as heartburn and acid reflux were present in 25 patients (55.6%), and patients without esophageal symptoms were 20 (44.4%). The degree of endoscopic abnormality was not significantly different between groups with or without esophageal symptoms. The improvement of symptoms was seen in 44 patients (97.8%) except 1 patient after administration of PPIs. The number of patients classified to the low-dose group was 7 patients (15.6%) and that of patients classified to the standard-dose group was 38 patients (84.4%). The follow-up pulmonary function test, peak expiratory flow rate (L/sec) was improved in 3 patients (3 of 7, 42.9%) of the low-dose group, and in 24 patients (24 of 38, 63.2%) of the standard-dose group. The improvement of ventilatory function was not significantly different according to dose of PPIs. CONCLUSIONS: Treatment with PPIs is expected to improve subjective symptoms and ventilatory function in asthma patients. PMID- 22042418 TI - [Clinical factors predicting for neoplastic transformation of gastric hyperplastic polyps]. AB - BACKGROUND/AIMS: Hyperplastic polyps (HPs) are the most common cause of all benign epithelial gastric polyps, constituting 30 to 93%. Although gastric HPs are usually considered as benign lesions compared with adenoma, neoplastic transformation has been known to occur rarely. We aimed to identify the clinical factors of gastric HPs predicting for neoplastic transformation. METHODS: Between January 2002 to August 2010, a total of 274 gastric HPs, which had been removed by endoscopic polypectomy or surgical resection from 210 patients, were analyzed retrospectively. RESULTS: Neoplastic transformation was found in 15 cases (5.5%) of 274 HPs including 10 cases of low grade dysplasia (3.7%), 2 cases of high grade dysplasia (0.7%) and 3 cases of adenocarcinoma (1.1%). Neoplastic transformations were significantly associated with >1 cm in size (n=10 [66.7%] vs. n=91 [35.1%], p=0.024), with pedunculated shape (n=9 [60.0%] vs. n=62 [23.9%], p=0.002), with previous history of gastrectomy (n=3 [20.0%] vs. n=3 [1.2%], p=0.002) and with synchronous neoplastic lesions occurring elsewhere in the gastric mucosa (n=5 [33.3%] vs. n=31 [12.0%], p=0.021). However, no significant difference was found between HPs with and without neoplastic transformation in terms of age, sex, number of polyps detected per patient, location, macroscopic appearance such as erosion, hyperemia. CONCLUSIONS: Neoplastic transformation of gastric HPs had significant relationships with ?1 cm in size, pedunculated shape, postgastectomy state, and synchronous neoplastic lesion. Therefore, endoscopic polypectomy should be considered in these HPs to avoid the risk of missing HPs with neoplastic potential. PMID- 22042419 TI - [MicroRNA expression pattern in intraductal papillary mucinous neoplasm]. AB - BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms (IPMN) are precursor lesions of fatal pancreatic cancer. Physiological function of microRNA is to regulate the stability and translation of mRNA. The aberrant microRNA expression is commonly observed in many cancers. The aim of this study was to analyze the expression pattern of microRNA in IPMN and evaluate the role of the microRNA. METHODS: Using two paraffin-embedded IPMN tissues, microRNA expression of normal tissue, IPMN adenoma and carcinoma were compared by cDNA-mediated annealing, selection, extension and ligation microarray assay. Using real time PCR, expression levels of aberrantly up-regulated microRNAs were assessed in another 20 IPMNs, four pancreatic cancer cell lines (Panc1, MiaPaCa-2, XPA-3, BxPC-3) and immortalized pancreatic ductal cell line (HPNE). Effect of suppressing highly over-expressed two microRNAs in pancreatic cancer cell lines with anti-microRNA inhibitors were evaluated using CCK-8 assay. RESULTS: Among aberrantly expressed 122 microRNAs in IPMN, miR-552, miR-25*, miR-183, miR-1300, miR-196a, miR-182*, and miR-30c-1* were consistently increased more than 3-fold. On average, miR-196a and miR-183 increased 10,824 folds and 26,519 folds in four pancreatic cancer cell lines compared with HPNE. These two microRNAs were also over-expressed in 20 IPMNs compared with HPNE. After applying anti-miRNA inhibitors, cell survival of four pancreatic cancer cell lines decreased by 24.5% with anti-miR-196a and by 14.2% with anti-miR-183 on average. CONCLUSIONS: Aberrant expression of 122 microRNAs was observed in IPMN. Two microRNAs, miR-196a and miR-183-increased in IPMN and pancreatic cancer cell lines compared with immortalized dancreatic ductal cell line. The inhibitions of these microRNAs repressed cell proliferation of pancreatic cancer cell lines. (Korean J Gastroenterol 2011;58:190-200). PMID- 22042421 TI - [A case of gastric lymphoepithelioma-like carcinoma presenting as panperitonitis by perforation of stomach]. AB - Gastric lymphoepithelioma-like carcinoma is a rare carcinoma among gastric malignant tumor but has a good prognosis. The carcinoma has histologic feature characterized by small nest of cancer cells mixed with lymphoid stroma. We report a case with lymphoepithelioma-like carcinoma of stomach initially presenting as panperitonitis because of spontaneous tumor perforation. A 56-year-old man visited our emergency room because of epigastric pain. A preoperative abdominal CT scan showed a massive pneumoperitoneum in the upper abdomen, and the presence of gastric cancer in the lesser curvature of the stomach. An emergent laparotomy was performed followed by radical subtotal gastrectomy. Pathologic examination revealed that the tumor was a lymphoepithelioma-like gastric carcinoma. PMID- 22042420 TI - [The effect of periampullary diverticulum on the outcome of bile duct stone treatment with endoscopic papillary large balloon dilation]. AB - BACKGROUND/AIMS: Periampullary diverticulum (PAD) causes difficulty in the extraction of common bile duct (CBD) stones with conventional endoscopic therapy. Our study was designed to evaluate the effect of PAD on endoscopic large balloon dilation (EPLBD) with/without limited endoscopic sphincterotomy (EST) for CBD stone treatment. METHODS: We retrospectively reviewed cases of 141 patients treated CBD stones by EPLBD with/without limited EST at Gachon Gil Medical Center from September 2008 to February 2010. PAD were classified into three groups according to the location of the papilla and diverticulum. Clinical parameters, endoscopic parameters, and procedure outcomes were analyzed. RESULTS: PAD were identified in 46.1% (65/141), with 23 male (35.4%) and 42 female (64.6%) and a mean age of 72.9+/-11.1 years. Mean diameter of the stones was 14.8+/-6.0 mm and mean diameter of CBD was 21.6+/-7.7 mm. PAD group was significantly older than control group (72.9 vs. 68.6, p=0.043) and the incidence of large stone (>=15 mm) was higher in PAD group (60.0% vs. 42.1%, p=0.034). Success rate of complete removal of stones in the first session was 32/65 patients (49.2%) and overall successful complete stone removal rates was 63/65 (96.9%). There was no significant difference between the PAD and control groups in success rate. Major complications were similar between two groups. CONCLUSIONS: PAD is associated with an increased incidence of large bile duct stones and older age. PAD seems to not increase technical failure rate or complication risk on EPLBD with/without limited EST. PMID- 22042422 TI - Retroperitoneal hemorrhage after endoscopic removal of a fish bone stuck in the duodenum of a patient receiving hemodialysis. AB - Fish bones are often ingested accidently. Most of them passes out through the gastrointestinal tract safely, but serious complications, such as perforation, abscess, obstruction, and bleeding in the gastrointestinal tract, can occur. An ingested fish bone can be easily removed by endoscopy, and surgery is rarely required. However, there may be complications related to the endoscopic procedure including mucosal laceration, bleeding, fever, and perforation. Here, we report a case of retroperitoneal hemorrhage developed after endoscopic removal of a fish bone stuck in the duodenal wall, and then resolved spontaneously by conservative care. PMID- 22042423 TI - Small bowel carcinoma in young patient detected by double-balloon enteroscopy. AB - A 17-year old female presented with a chief complaint of melena and epigastric pain. She had a family history of colon cancer, her mother having been diagnosed with hereditary nonpolyposis colorectal carcinoma (HNPCC). After close examination including double-balloon enteroscopy, the patient was diagnosed with small bowel carcinoma, in spite of her young age. Here we report this rare case of small bowel carcinoma in a young patient with a family history of HNPCC. PMID- 22042424 TI - [A case of idiopathic sclerosing mesenteritis with retroperitoneal fibrosis]. AB - Sclerosing mesenteritis is a rare inflammatory disease of the bowel mesentery. It produces tumor-like masses of the mesentery composed of varying degrees of fibrosis, chronic inflammation, and fat necrosis. It has been described variously as fibrosing mesenteritis, retractile mesenteritis, mesenteric Weber Christian disease, and systemic nodular panniculitis. The etiology and pathogenesis of the disease are as yet unknown, but autoimmune disorder, previous abdominal surgery, trauma, and ischemia could play a role. The clinical features include abdominal pain, vomiting, diarrhea, and constipation. Occasionally, patients with this condition may present with bowel obstruction. Rarely, It can be associated with other idiopathic inflammatory disorders such as retroperitoneal fibrosis, sclerosing cholangitis, and orbital pseudotumors. We report a case of idiopathic sclerosing mesenteritis with retroperitoneal fibrosis in a 58-year-old man. PMID- 22042425 TI - [Eosinophilic liver abscess caused by Toxocara canis]. PMID- 22042427 TI - The reactivity of quaternary ammonium- versus potassium-fluorides supported on metal oxides: paving the way to an instantaneous detoxification of chemical warfare agents. AB - The reactions of the chemical warfare agents (CWAs) 2,2'-dichloroethyl sulfide (HD), O-ethyl S-2-(diisopropylamino)-ethyl methylphosphonothioate (VX) and isopropyl methylphosphonofluoridate (GB) with various metal oxide-supported quaternary ammonium fluorides (QAF) and/or potassium fluoride (KF) reagents are described. These active sorbents, which were prepared by a modified procedure, include alumina, silica and titania, enriched with "available" (not bound to the surface) fluoride ions. Alumina-based fluoride reagents were found to be more active than their silica or titania counterparts. QAF/Al(2)O(3) reagents, compared to KF/Al(2)O(3), exhibit an exceptional reactivity toward HD, as demonstrated both in reaction rates and product identity. For example, with TBAF, t(1/2) is 15 min for the formation of the elimination product divinyl sulfide (DVS), while with KF, t(1/2) is 10 h for the formation of the hydrolysis product thiodiglycol (TDG). On the other hand, both sorbents reacted similarly against the nerve agents GB or VX. In order to increase the "available" fluoride content on the solid surface, the mixed active sorbent TBAF/KF/Al(2)O(3) (20/20/60) was developed. On this powder, all three CWAs were degraded instantaneously at the low loading of 1 wt% (t(1/2) < 2 min) and rapidly at the higher loadings of 5-10 wt% (t(1/2) of minutes scale). We assume that the relatively large amount of inorganic fluoride (KF) acts synergistically as a reservoir for the more reactive organic fluorides (TBAF). Moreover, the alumina surface hydroxyl groups may also operate as a water reservoir for the hydrolysis of VX or GB. Therefore, TBAF/KF/Al(2)O(3) might be considered as a promising destructive sorbent for CWAs. PMID- 22042428 TI - Should we rely on OCT to assess the improvements of new generation drug-eluting stents? PMID- 22042429 TI - Self-gated PROPELLER-encoded cine cardiac imaging. AB - This study uses the k-space center over-sampling property of PROPELLER encoding to detect cardiac and respiratory motion using raw k-space data. Using the motion information, cine cardiac imaging is self-gated. The data acquisition process requires neither electrocardiography triggering nor patient breath-holding. Using physiology motion information, this post-processing method rearranges the k-space data into groups corresponding to cardiac and respiratory phases. The PROPELLER blades of the same groups are combined to produce cine high-resolution images. This approach reduces the potential discrepancy of the k-space data and the motion-related artifacts in the reconstructed image because all blades in a group are acquired at consistent cardiac and respiratory phases. The study concludes that self-gated cine cardiac imaging is feasible using PROPELLER encoding. It is a potentially practical tool for cine cardiac imaging. PMID- 22042430 TI - Next-generation sequencing reveals regional differences of the alpha-synuclein methylation state independent of Lewy body disease. AB - The alpha-synuclein gene (SNCA) plays a major role in the aetiology of Lewy body disease (LBD) including Parkinson's disease (PD). Point mutations and genetic alterations causing elevated gene expression are causally linked to familial PD. To what extent epigenetic changes play a role in the regulation of alpha synuclein expression and may contribute to the aetiology of sporadic LBD is a matter of debate. We analysed the methylation state of the promoter region and a CpG-rich region of intron 1 of alpha-synuclein in several brain regions in sporadic LBD and controls using 454 GS-FLX-based high-resolution bisulphite sequencing. Our results indicate that there are significant differences in the level of methylation between different brain areas. The overall methylation levels in the promoter and intron 1 of alpha-synuclein are rather low in controls and-in contrast to previously reported findings-are not significantly different from LBD. However, single CpG analysis revealed significant hyper- and hypomethylation at different positions in various brain regions and LBD stages. A slight overall increase in methylation related to LBD patients' age was detected. PMID- 22042431 TI - GENPLAT: an automated platform for biomass enzyme discovery and cocktail optimization. AB - The high cost of enzymes for biomass deconstruction is a major impediment to the economic conversion of lignocellulosic feedstocks to liquid transportation fuels such as ethanol. We have developed an integrated high throughput platform, called GENPLAT, for the discovery and development of novel enzymes and enzyme cocktails for the release of sugars from diverse pretreatment/biomass combinations. GENPLAT comprises four elements: individual pure enzymes, statistical design of experiments, robotic pipeting of biomass slurries and enzymes, and automated colorimeteric determination of released Glc and Xyl. Individual enzymes are produced by expression in Pichia pastoris or Trichoderma reesei, or by chromatographic purification from commercial cocktails or from extracts of novel microorganisms. Simplex lattice (fractional factorial) mixture models are designed using commercial Design of Experiment statistical software. Enzyme mixtures of high complexity are constructed using robotic pipeting into a 96-well format. The measurement of released Glc and Xyl is automated using enzyme-linked colorimetric assays. Optimized enzyme mixtures containing as many as 16 components have been tested on a variety of feedstock and pretreatment combinations. GENPLAT is adaptable to mixtures of pure enzymes, mixtures of commercial products (e.g., Accellerase 1000 and Novozyme 188), extracts of novel microbes, or combinations thereof. To make and test mixtures of ~10 pure enzymes requires less than 100 MUg of each protein and fewer than 100 total reactions, when operated at a final total loading of 15 mg protein/g glucan. We use enzymes from several sources. Enzymes can be purified from natural sources such as fungal cultures (e.g., Aspergillus niger, Cochliobolus carbonum, and Galerina marginata), or they can be made by expression of the encoding genes (obtained from the increasing number of microbial genome sequences) in hosts such as E. coli, Pichia pastoris, or a filamentous fungus such as T. reesei. Proteins can also be purified from commercial enzyme cocktails (e.g., Multifect Xylanase, Novozyme 188). An increasing number of pure enzymes, including glycosyl hydrolases, cell wall-active esterases, proteases, and lyases, are available from commercial sources, e.g., Megazyme, Inc. (www.megazyme.com), NZYTech (www.nzytech.com), and PROZOMIX (www.prozomix.com). Design-Expert software (Stat Ease, Inc.) is used to create simplex-lattice designs and to analyze responses (in this case, Glc and Xyl release). Mixtures contain 4-20 components, which can vary in proportion between 0 and 100%. Assay points typically include the extreme vertices with a sufficient number of intervening points to generate a valid model. In the terminology of experimental design, most of our studies are "mixture" experiments, meaning that the sum of all components adds to a total fixed protein loading (expressed as mg/g glucan). The number of mixtures in the simplex-lattice depends on both the number of components in the mixture and the degree of polynomial (quadratic or cubic). For example, a 6-component experiment will entail 63 separate reactions with an augmented special cubic model, which can detect three-way interactions, whereas only 23 individual reactions are necessary with an augmented quadratic model. For mixtures containing more than eight components, a quadratic experimental design is more practical, and in our experience such models are usually statistically valid. All enzyme loadings are expressed as a percentage of the final total loading (which for our experiments is typically 15 mg protein/g glucan). For "core" enzymes, the lower percentage limit is set to 5%. This limit was derived from our experience in which yields of Glc and/or Xyl were very low if any core enzyme was present at 0%. Poor models result from too many samples showing very low Glc or Xyl yields. Setting a lower limit in turn determines an upper limit. That is, for a six-component experiment, if the lower limit for each single component is set to 5%, then the upper limit of each single component will be 75%. The lower limits of all other enzymes considered as "accessory" are set to 0%. "Core" and "accessory" are somewhat arbitrary designations and will differ depending on the substrate, but in our studies the core enzymes for release of Glc from corn stover comprise the following enzymes from T. reesei: CBH1 (also known as Cel7A), CBH2 (Cel6A), EG1(Cel7B), BG (beta-glucosidase), EX3 (endo-beta1,4-xylanase, GH10), and BX (beta-xylosidase). PMID- 22042432 TI - Measurement of tumour necrosis factor receptors for immune response in colon cancer patients. AB - Immune system is crucial to tumour's initiation, progress and establishment and is contributing to prevent upcoming damaging invasion. Tumour development and surgical resection are both immunosuppressive processes. Immune response could be evaluated by ex vivo lipopolysaccharide (LPS) test, measuring cytokines and receptors release. The aim of the study is to investigate the postoperative immune recovery of cancer patients upon discharge. Twenty-two patients with colon cancer, without pre-treatment, and 16 healthy volunteers (HV) were enrolled in the study. Ten ml of whole blood were collected from every patient on admission (PRE) and upon discharge (POD7) and every HV. Diluted whole blood samples were stimulated with 500 pg/ml LPS, at 37 degrees C, for 4H. Cell culture supernatants (CCSP) were removed after centrifugation and stored at -70 degrees C. Tumour necrosis factor-alpha (TNF-alpha), interleukin-6 and interleukin-10 (IL-6, IL 10), soluble TNF receptors (sTNFRs) were measured in serum and CCSP by enzymelinked immunosorbent assay. Serum cytokines and receptors, PRE and POD7, were significantly elevated compared to HV (P < 0.001) and significant correlations were found between POD7 IL-6 and sTNFRs (Spearman's rho 0.47, P < 0.05). Ex vivo, TNF-alpha, IL-6 and TNFRI release were lower either PRE or POD7, while IL-10 and TNFRII were higher, than in HV. No significant differences (P > 0.05) were found between PRE and POD7 levels in serum or CCSP. Cancer patients are not postoperatively immune restored until discharge. The trend of anti inflammatory TNFRs release could account for alternative marker for the control of cancer patients immune response and the schedule of their following therapeutic treatment. PMID- 22042433 TI - Bioinformatic survey of Haliotis midae microsatellites reveals a non-random distribution of repeat motifs. AB - Recent studies have shown the non-random distribution of microsatellite motifs between genomic regions within a particular species. This study investigates such microsatellite distributions in the genome of the economically important abalone Haliotis midae, via a bioinformatic survey. In particular, the association of specific repeat motifs to coding regions and transposable elements is investigated. An understanding of microsatellite genomic distribution will facilitate more efficient use and development of this popular molecular marker. A bias toward di- and tetranucleotide repeats was found in the H. midae genome. CA microsatellite units were the most abundant repeat motif, but were notably underrepresented in genic regions where GAGT repeats predominate. Approximately 17.5% and 21% of the microsatellites showed gene and/or transposable element associations, respectively. This could explain the high genomic frequencies of particular motifs across the genome and may allude to a possible functional role. The data presented in this study are the first to demonstrate such non-random dispersal of microsatellites in abalone and support previous findings arguing in favor of non-random distribution of repeat motifs. PMID- 22042434 TI - Anchor ice and benthic disturbance in shallow Antarctic waters: interspecific variation in initiation and propagation of ice crystals. AB - Sea ice typically forms at the ocean's surface, but given a source of supercooled water, an unusual form of ice--anchor ice--can grow on objects in the water column or at the seafloor. For several decades, ecologists have considered anchor ice to be an important agent of disturbance in the shallow-water benthic communities of McMurdo Sound, Antarctica, and potentially elsewhere in polar seas. Divers have documented anchor ice in the McMurdo communities, and its presence coincides with reduced abundance of the sponge Homaxinella balfourensis, which provides habitat for a diverse assemblage of benthic organisms. However, the mechanism of this disturbance has not been explored. Here we show interspecific differences in anchor-ice formation and propagation characteristics for Antarctic benthic organisms. The sponges H. balfourensis and Suberites caminatus show increased incidence of formation and accelerated spread of ice crystals compared to urchins and sea stars. Anchor ice also forms readily on sediments, from which it can grow and adhere to organisms. Our results are consistent with, and provide a potential first step toward, an explanation for disturbance patterns observed in shallow polar benthic communities. Interspecific differences in ice formation raise questions about how surface tissue characteristics such as surface area, rugosity, and mucus coating affect ice formation on invertebrates. PMID- 22042435 TI - Properties of bacteria that trigger hemocytopenia in the Atlantic blue crab, Callinectes sapidus. AB - In the blue crab Callinectes sapidus, injection with the bacterial pathogen Vibrio campbellii causes a decrease in oxygen consumption. Histological and physiological evidence suggests that the physical obstruction of hemolymph flow through the gill vasculature, caused by aggregations of bacteria and hemocytes, underlies the decrease in aerobic function associated with bacterial infection. We sought to elucidate the bacterial properties sufficient to induce a decrease in circulating hemocytes (hemocytopenia) as an indicator for the initiation of hemocyte aggregation and subsequent impairment of respiration. Lipopolysaccharide (LPS), the primary component of the gram-negative bacterial cell wall, is known to interact with crustacean hemocytes. Purified LPS was covalently bound to the surfaces of polystyrene beads resembling bacteria in size. Injection of these "LPS beads" caused a decrease in circulating hemocytes comparable to that seen with V. campbellii injection, while beads alone failed to do so. These data suggest that in general, gram-negative bacteria could stimulate hemocytopenia. To test this hypothesis, crabs were injected with different bacteria--seven gram negative and one gram-positive species--and their effects on circulating hemocytes were assessed. With one exception, all gram-negative strains caused decreases in circulating hemocytes, suggesting an important role for LPS in the induction of this response. However, LPS is not necessary to provoke the immune response given that Bacillus coral, a gram-positive species that lacks LPS, caused a decrease in circulating hemocytes. These results suggest that a wide range of bacteria could impair metabolism in C. sapidus. PMID- 22042436 TI - Metamorphic remodeling of a planktotrophic larva to produce the predatory feeding system of a cone snail (Mollusca, Neogastropoda). AB - I used histological sections and 3D reconstructions to document development through metamorphosis of the foregut and proboscis in the conoidean neogastropod Conus lividus. A goal was to determine how highly derived features of the post metamorphic feeding system of this gastropod predator develop without interfering with larval structures for microherbivory. A second goal was to compare foregut development in this conoidean with previous observations on foregut development in the buccinoidean neogastropod Nassarius mendicus. These two neogastropods both have a feeding larval stage, but they show major differences in post-metamorphic foregut morphology. Basic events in development of the proboscis and proboscis sheath in C. lividus and N. mendicus were similar. However, the elongate buccal tube of C. lividus forms during metamorphosis as a composite of apical epidermal tissue that grows inward and ventral foregut tissue that extends outward. The larval mouth is not carried through metamorphosis. Comparative observations on foregut development in caenogastropods, which now include data on C. lividus, suggest that the foregut incorporates dorsal and ventral modules having different ontogenetic and functional fates. This developmental modularity may have facilitated evolutionary diversification of the post-metamorphic foregut. Foregut diversification in predatory gastropods may have been further fast-tracked by developmental uncoupling of larval and post-metamorphic mouths. PMID- 22042437 TI - Effects of temperature on hatching time and hatchling proportions in a poecilogonous population of Haminoea zelandiae. AB - Poecilogony is a relatively uncommon life-history strategy that results in the production of two different larval forms from the same egg mass (e.g., free swimming lecithotrophic larvae and post-metamorphic, crawling juveniles). In this study, a population of the opisthobranch gastropod Haminoea zelandiae from Pauatahanui Inlet, New Zealand, was found to exhibit poecilogony. Further, differences in development, hatching times and proportion of hatchlings that were veligers or juveniles were examined for egg masses in two temperature regimes in the laboratory: cool (15-17 degrees C), and warm (21-23 degrees C). Hatching proportions were also examined for egg masses collected from the field (where temperatures ranged from 21-23 degrees C) for varying lengths of time (1 d, 5 d, and 10 d post-spawning). Hatchlings from egg masses in warmer temperatures developed faster and hatched earlier than those in cool temperatures. In the laboratory, egg masses in warm conditions hatched a greater proportion of post metamorphic juveniles (45.4%) compared to egg masses in cool conditions (24.6%) Further, egg masses that had been in the field 10 d before hatching (i.e., more days at warmer temperatures) exhibited a greater proportion of post-metamorphic juveniles (67.9%) than those that were collected after only 1 d in the field (25.1%). Together these results suggest that temperature may have an important role in mediating dispersal strategies in this poecilogonous species. PMID- 22042438 TI - Spermatozoon ultrastructure of Gyliauchen sp. (Digenea: Gyliauchenidae), an intestinal parasite of Siganus fuscescens (Pisces: Teleostei). AB - The ultrastructure of the mature spermatozoon of Gyliauchen sp., a parasite of the dusky rabbitfish Siganus fuscescens, was studied by transmission electron microscopy. The spermatozoon possesses two axonemes of the 9+"1" pattern of Trepaxonemata, four attachment zones, one mitochondrion, a nucleus, cortical microtubules, external ornamentation of the plasma membrane, and spine-like bodies. The main characteristics of this spermatozoon are the presence of one mitochondrion, spine-like bodies not associated with the external ornamentation, and a posterior extremity of type 3 that is characterized by the following sequence: posterior extremity of the nucleus then posterior extremity of the second axoneme. Numerous other ultrastructural features are also discussed and compared to the digenean spermatology literature. This is the first study of a member of the Gyliauchenidae and the fourth within the Lepocreadioidea. The results show that many ultrastructural characters are variable within this superfamily and could be useful for phylogeny. PMID- 22042439 TI - Embryonic development and expression analysis of Distal-less in Caprella scaura (Crustacea, Amphipoda, Caprellidea). AB - The Caprellidea generally possess rudimentary abdomens and degenerated third and fourth pereopods. Previous molecular phylogenetic studies support the concept that their unique body plan is derived from a gammarid-like body plan from which the abdomen or third and fourth pereopods have been lost in the Caprellidea. To understand the developmental and genetic mechanisms for the morphological evolution of the Caprellidea, we observed the embryonic development of Caprella scaura. Although in the early embryonic stage limb buds appeared in all of the pereonites, we found that elongation of the limb buds did not occur in the third and fourth pereonites; instead, only oval projections (possibly primordial gills) were observed. We next examined the gene expression of Distal-less (Dll) by in situ hybridization and found that Dll was not expressed in the third and fourth pereonites. This suggests that the suppression of Dll expression is responsible for the reduction of Caprellidea pereopods. PMID- 22042440 TI - Neurogenesis in the procerebrum of the snail Helix aspersa: a quantitative analysis. AB - The procerebrum, a specialized structure for olfaction in terrestrial pulmonate molluscs, contains 20,000 to 50,000 small, uniformly sized neurons that increase in number with age. Here I show the likely source of neurons added to the procerebrum of Helix aspersa and that the rate of neuron addition depends on snail weight. After hatching, during the initial exponential growth phase, H. aspersa adds neurons to the procerebral apex by mitosis and from a cerebral tube. In the logistic growth phase beginning 30-40 days post-hatch, neurons also seem to be added to the procerebrum from the peritentacular and olfactory nerves, causing the rate of neuron addition to approximately double; but as in the earlier exponential growth phase, this rate remains a function of snail weight. This neuron addition throughout the life of the snail can be predicted by snail weight. In the two growth phases, the number of neurons in the procerebrum is given by logarithmic functions of snail weight. The results here for H. aspersa provide the basis for experiments to determine the peripheral origin and destination of neuronal precursors that are added to the procerebrum and to determine how neuron addition affects the function of the procerebrum. PMID- 22042441 TI - Accumulation of the major yolk protein and zinc in the agametogenic sea urchin gonad. AB - Sea urchins of both sexes store the nutrients necessary for gametogenesis in nutritive phagocytes of the agametogenic gonad. A zinc-binding protein termed the major yolk protein (MYP) is stored here as two isoforms: the egg-type (predominant in egg yolk granules) and the coelomic fluid-type (a precursor with greater zinc-binding capacity). MYP is used during gametogenesis as material for synthesizing gametic proteins and other components. We investigated its accumulation and relationship to zinc contents in gonads during the non reproductive season in Pseudocentrotus depressus. MYP constituted most of the protein in coelomic fluid and gonads. Both ovaries and testes grew gradually, accumulating MYP and zinc during the year. Total zinc contents and the ratio of coelomic fluid-type to egg-type protein were higher in ovaries than in testes as gametogenesis approached. Most of the zinc in the coelomic fluid was bound to MYP, and the concentrations of MYP and zinc were elevated toward the onset of oogenesis in the female coelomic fluid. Thus, MYP accumulates in the agametogenic ovaries and testes during the non-reproductive season, playing a role as a carrier to transport zinc to the gonad. Transportation of zinc by MYP is more active in females than in males. PMID- 22042442 TI - Contribution of matrix metalloproteinase 2 to joint destruction in group B Streptococcus-induced murine arthritis. AB - OBJECTIVE: To assess the role of matrix metalloproteinase 2 (MMP-2) in the evolution of septic arthritis induced by group B streptococci (GBS) in mice. METHODS: Mice deficient in MMP-2 (MMP-2(-/-) ) and wild-type controls were injected intravenously with 1 * 10(7) colony-forming units of type IV GBS (strain 1/82). Levels of MMP-2, mortality rates, evolution of arthritis, bacterial clearance, joint histopathologic features, and production of cytokines and chemokines were examined in both experimental groups of mice on days 3, 6, and 9 after infection. RESULTS: MMP-2 was produced during GBS infection. Disruption of the gene for MMP-2 resulted in a decrease in the incidence and severity of arthritis, as demonstrated by both clinical and histologic findings, without affecting mortality rates. Amelioration of arthritis was accompanied by a dramatic reduction in the local production of interleukin-1beta (IL-1beta), IL-6, macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-2 and a reduced bacterial burden. CONCLUSION: MMP-2, produced early during GBS infection in mice, is involved in the degradation of extracellular matrix components at the level of the joint. This degradation is the first step in a cascade of events (joint invasion by GBS, extravasation and accumulation of inflammatory cells, proinflammatory cytokine production), all of which contribute to the damage of articular tissue. Thus, MMP-2 should be regarded as a potential therapeutic target in GBS-induced arthritis. PMID- 22042443 TI - Redundant information encoding in primary motor cortex during natural and prosthetic motor control. AB - Redundant encoding of information facilitates reliable distributed information processing. To explore this hypothesis in the motor system, we applied concepts from information theory to quantify the redundancy of movement-related information encoded in the macaque primary motor cortex (M1) during natural and neuroprosthetic control. Two macaque monkeys were trained to perform a delay center-out reaching task controlling a computer cursor under natural arm movement (manual control, 'MC'), and using a brain-machine interface (BMI) via volitional control of neural ensemble activity (brain control, 'BC'). During MC, we found neurons in contralateral M1 to contain higher and more redundant information about target direction than ipsilateral M1 neurons, consistent with the laterality of movement control. During BC, we found that the M1 neurons directly incorporated into the BMI ('direct' neurons) contained the highest and most redundant target information compared to neurons that were not incorporated into the BMI ('indirect' neurons). This effect was even more significant when comparing to M1 neurons of the opposite hemisphere. Interestingly, when we retrained the BMI to use ipsilateral M1 activity, we found that these neurons were more redundant and contained higher information than contralateral M1 neurons, even though ensembles from this hemisphere were previously less redundant during natural arm movement. These results indicate that ensembles most associated to movement contain highest redundancy and information encoding, which suggests a role for redundancy in proficient natural and prosthetic motor control. PMID- 22042445 TI - Translation and validation of Korean Functional Assessment of Cancer Therapy Esophageal (FACT-E) scale with squamous cell carcinoma and chemoradiation-only patients. AB - PURPOSE: The Functional Assessment of Cancer Therapy-Esophageal (FACT-E) Scale version 4 has been used to assess quality of life in patients with squamous cell carcinoma undergoing chemoradiation. We sought to determine whether this scale can be used to assess quality of life in Korean patients with esophageal cancer undergoing chemoradiation. METHODS: The FACT-E scale version 4 was cross culturally translated into Korean. Its reliability and validity were assessed in a group of 146 esophageal cancer patients who were scheduled for neoadjuvant chemoradiation (CRT). This procedure was followed by esophagectomy that took place between 2007 and 2010 at Asan Medical Center. All patients completed the FACT-E, Hospital Anxiety and Depression Scale (HADS) and Functional Living Index Cancer (FLIC) questionnaires at baseline (pre-treatment) and 1 month after two cycles of induction chemotherapy followed by CRT. RESULTS: In validating the FACT E, we found high internal consistency coefficients ranging from 0.72 to 0.91. Good convergent and divergent validities were demonstrated by the FLIC and HADS scales. The FACT-E showed good clinical validity and effectively differentiated between patient groups with different performance status ratings and stages. Changes in clinical status were reflected by changes in FACT-E scores, demonstrating responsiveness to neoadjuvant CRT. CONCLUSION: The FACT-E has been shown to be a reliable and valid instrument that can now be used to prospectively evaluate the quality of life of Korean patients with esophageal cancer. PMID- 22042444 TI - Energy-based stochastic control of neural mass models suggests time-varying effective connectivity in the resting state. AB - Several studies posit energy as a constraint on the coding and processing of information in the brain due to the high cost of resting and evoked cortical activity. This suggestion has been addressed theoretically with models of a single neuron and two coupled neurons. Neural mass models (NMMs) address mean field based modeling of the activity and interactions between populations of neurons rather than a few neurons. NMMs have been widely employed for studying the generation of EEG rhythms, and more recently as frameworks for integrated models of neurophysiology and functional MRI (fMRI) responses. To date, the consequences of energy constraints on the activity and interactions of ensembles of neurons have not been addressed. Here we aim to study the impact of constraining energy consumption during the resting-state on NMM parameters. To this end, we first linearized the model, then used stochastic control theory by introducing a quadratic cost function, which transforms the NMM into a stochastic linear quadratic regulator (LQR). Solving the LQR problem introduces a regime in which the NMM parameters, specifically the effective connectivities between neuronal populations, must vary with time. This is in contrast to current NMMs, which assume a constant parameter set for a given condition or task. We further simulated energy-constrained stochastic control of a specific NMM, the Wilson and Cowan model of two coupled neuronal populations, one of which is excitatory and the other inhibitory. These simulations demonstrate that with varying weights of the energy-cost function, the NMM parameters show different time-varying behavior. We conclude that constraining NMMs according to energy consumption may create more realistic models. We further propose to employ linear NMMs with time varying parameters as an alternative to traditional nonlinear NMMs with constant parameters. PMID- 22042446 TI - Sex differences and left-right asymmetries in expression of insulin and insulin like growth factor-1 receptors in developing rat hippocampus. AB - Sex differences and laterality of rat hippocampus with respect to insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (InsR) expression as two important contributors to/regulators of developmental and cognitive functions were examined using real-time PCR and western blot analysis at P0, P7 and P14. Expression of the IGF-1R gene was lowest at P0 in all studied hippocampi. In males, we found the highest expression at P7 in the right hippocampus, and at P14 in the left one. In contrast, the peaked IGF-1R expression occurred at P7 in female hippocampi independent of laterality. Hippocampal InsR expression in males decreased significantly between P0 and P7, followed by a marked upregulation at P14. Conversely, the expression of InsR in females peaked at P7 and then decreased again significantly at P14. We found significant interhemispheric differences in IGF-1R mRNA levels in both male and female hippocampi at different time points. In contrast, we only found significant interhemispheric differences in InsR mRNA expression in P14 male rats, with higher values in the left hippocampus. Interestingly, changes in mRNA expression and in protein levels followed the same developmental pattern, indicating that IGF-1R and InsR transcription is not subject to modulatory effects during the first two weeks of development. These findings indicate that there are prominent interhemispheric and sex differences in IGF-1R and InsR expression in the developing rat hippocampus, suggesting a probable mechanism for the control of gender and laterality differences in development and function of the hippocampus. PMID- 22042448 TI - [Second line AUO (Working Group Urological Oncology) study AB 35/09 on metastasized urothelial carcinoma. Phase II study with RAD001 in combination with paclitaxel for patients with metastasized urothelial carcinoma of the urinary bladder after failure of platinum-based chemotherapy (CRAD001)]. PMID- 22042447 TI - The phosphoinositide phosphatase Sac1 is required for midline axon guidance. AB - Sac1 phosphoinositide (PI) phosphatases are important regulators of PtdIns(4)P turnover at the ER, Golgi, and plasma membrane (PM) and are involved in diverse cellular processes including cytoskeletal organization and vesicular trafficking. Here, we present evidence that Sac1 regulates axon guidance in the embryonic CNS of Drosophila. Sac1 is expressed on three longitudinal axon tracts that are defined by the cell adhesion molecule Fasciclin II (Fas II). Mutations in the sac1 gene cause ectopic midline crossing of Fas II-positive axon tracts. This phenotype is rescued by neuronal expression of wild-type Sac1 but not by a catalytically-inactive mutant. Finally, sac1 displays dosage-sensitive genetic interactions with mutations in the genes that encode the midline repellent Slit and its axonal receptor Robo. Taken together, our results suggest that Sac1 mediated regulation of PIs is critical for Slit/Robo-dependent axon repulsion at the CNS midline. PMID- 22042453 TI - Investigation of factors affecting loosening of Ilizarov ring-wire external fixator systems at the bone-wire interface. AB - The potential for peri-implant bone yielding and subsequent loosening of Ilizarov ring-wire external fixation systems was investigated using non-linear finite element (FE) analyses. A strain-based plasticity model was employed to simulate bone yielding. FE models also incorporated contact behavior at the wire-bone interface, orthotropic elasticity, and periosteal-endosteal variation of bone properties. These simulations were used to determine the extent and location of yielding with change in age-related bone structure and properties for the bone Ilizarov construct at the tibial midshaft. At critical wire-bone interfaces, the predicted volume of yielded bone with four wires (on either side of the fracture) was ~40% of that with two wires. Old-aged cases showed considerably greater bone yielding at the wire-bone interface than young cases (1.7-2.2 times greater volumes of yielded bone). The volume of yielded bone at all wire-bone interfaces decreased with an increase in wire pre-tension. The absence of continuous through thickness yielding offers an explanation for the clinical observation that Ilizarov ring-wire fixation can provide stable fracture fixation even in bone with high porosity. PMID- 22042454 TI - Retrievable inferior vena cava filters: factors that affect retrieval success. AB - PURPOSE: To report and analyze the indications, procedural success, and complications of retrievable inferior vena cava filters (rIVCF) placement and to identify parameters that influence retrieval attempt and failure. METHODS: Between January 2005 and December 2010, a total of 200 patients (80 men, median age 67 years, range 11-95 years) received a rIVCF with the clinical possibility that it could be removed. All patients with rIVCF were prospectively entered into a database and followed until retrieval or a decision not to retrieve the filter was made. A retrospective analysis of this database was performed. RESULTS: Sixty one percent of patients had an accepted indication for filter placement; 39% of patients had a relative indication. There was a tendency toward a higher retrieval rate in patients with relative indications (40% vs. 55%, P = 0.076). Filter placement was technically successful in all patients, with no procedure related mortality. The retrieval rate was 53%. Patient age of >80 years (odds ratio [OR] 0.056, P > 0.0001) and presence of malignancy (OR 0.303, P = 0.003) was associated with a significantly reduced probability for attempted retrieval. Retrieval failure occurred in 7% (6 of 91) of all retrieval attempts. A time interval of > 90 days between implantation and attempted retrieval was associated with retrieval failure (OR 19.8, P = 0.009). CONCLUSIONS: Patient age >80 years and a history of malignancy are predictors of a reduced probability for retrieval attempt. The rate of retrieval failure is low and seems to be associated with a time interval of >90 days between filter placement and retrieval. PMID- 22042455 TI - A fast and selective decarboxylative difunctionalization and cyclization for easy access to gem-dihalo alcohol, ether, ester and bromo-1,4-dioxane. AB - A general strategy for fast decarboxylative difunctionalization to gem dihalohydrin, gem-dihaloether, gem-dibromoester and cyclized bromo-1,4-dioxane synthons with outstanding regio- and stereoselectivity is demonstrated. PMID- 22042456 TI - Preparation of chitosan films using different neutralizing solutions to improve endothelial cell compatibility. AB - The development of chitosan-based constructs for application in large-size defects or highly vascularized tissues is still a challenging issue. The poor endothelial cell compatibility of chitosan hinders the colonization of vascular endothelial cells in the chitosan-based constructs, and retards the establishment of a functional microvascular network following implantation. The aim of the present study is to prepare chitosan films with different neutralization methods to improve their endothelial cell compatibility. Chitosan salt films were neutralized with either sodium hydroxide (NaOH) aqueous solution, NaOH ethanol solution, or ethanol solution without NaOH. The physicochemical properties and endothelial cell compatibility of the chitosan films were investigated. Results indicated that neutralization with different solutions affected the surface chemistry, swelling ratio, crystalline conformation, nanotopography, and mechanical properties of the chitosan films. The NaOH ethanol solution neutralized chitosan film (Chi-NaOH/EtOH film) displayed a nanofiber-dominant surface, while the NaOH aqueous solution-neutralized film (Chi-NaOH/H(2)O film) and the ethanol solution-neutralized film (Chi-EtOH film) displayed nanoparticle dominant surfaces. Moreover, the Chi-NaOH/EtOH films exhibited a higher stiffness as compared to the Chi-NaOH/H(2)O and Chi-EtOH films. Endothelial cell compatibility of the chitosan films was evaluated with a human microvascular endothelial cell line, HMEC-1. Compared with the Chi-NaOH/H(2)O and Chi-EtOH films, HMECs cultured on the Chi-NaOH/EtOH films fully spread and exhibited significantly higher levels of adhesion and proliferation, with retention of the endothelial phenotype and function. Our findings suggest that the surface nanotopography and mechanical properties contribute to determining the endothelial cell compatibility of chitosan films. The nature of the neutralizing solutions can affect the physicochemical properties and endothelial cell compatibility of chitosan films. Therefore, selection of suitable neutralization methods is highly important for the application of chitosan in tissue engineering. PMID- 22042457 TI - Ex vivo bio-compatibility of honey-alginate fibrous matrix for HaCaT and 3T3 with prime molecular expressions. AB - Honey's inherent compositional diversity, bio-compatibility and time tested therapeutic efficacy, especially in tissue repair as a topical agent, attract researchers towards harnessing its biomaterial potential particularly in developing matrix for tissue engineering applications. Hence, this study fabricates fibrous mat from optimum honey-alginate formulation and alginate solution using wet spinning technology. The physical and morphological properties of the scaffolds are assessed and finally their comparative biological performances are evaluated through in vitro studies on adherence, viability and prime molecular expression of HaCaT and 3T3 cells. The honey-alginate scaffold demonstrates better performance than that of alginate in terms of cellular adherence, viability and proper expression of cell-cell adhesion molecule (E cadherin) and prime molecules of extra cellular matrix (Collagen I and III) by HaCaT and 3T3 respectively. PMID- 22042458 TI - Influence of topographical features on the fluoride corrosion of Ni-Ti orthodontic archwires. AB - Different manufacturing processes of Ni-Ti archwires respond differently to corrosion due to the surface conditions involved. In this study, several topographical features and their influence upon fluoride corrosion were studied. Four topographies (smooth, dimple, scratch, and crack) according to the main surface defect were characterized (n = 40). Static corrosion tests were performed in artificial saliva with fluorated prophylactic gel (12500 ppm) for 28 days. The surface was characterized by SEM and laser confocal microscopy. Standard electrochemical corrosion (open circuit potential, corrosion potential and corrosion current density) was performed. Statistical analysis was carried out using the ANOVA test (alpha <= 0.05). An increase was observed in the surface defects and/or roughness of the cracked and scratched surfaces. These defects produced an important increase in corrosion behavior. The best surfaces for the orthodontic archwires were the smooth and dimpled surfaces, respectively. The increase in defects was independent of roughness. Manufacturing processes that produce surface cracks should be avoided in orthodontic applications. PMID- 22042459 TI - High speed insertion of bone fracture fixation pins: a finite element penetration model with experimental comparisons. AB - A new method of bone fracture fixation is considered in which small pins/darts are dynamically inserted into bone to prevent translation and rotation at the fracture site. An ABAQUS model was developed to analyze dart penetration in cortical and cancellous bone for varying dart diameter, material, and velocity, and cortical thickness. The method is advocated for bioresorbable darts, so polylactide (PLA) and magnesium are the materials examined in this study. Numerical results showed that magnesium darts can achieve full penetration in bone while suffering little damage. The PLA darts penetrated thin bone well, but substantial deformation was seen as the cortical thickness increased, especially for small diameter darts. As partial validation, prototype PLA fixation darts were fired into cadaveric bone with a custom nailer. As in the model, the PLA darts could penetrate thin cortices but saw gross deformation when impacted against thicker bone. PMID- 22042461 TI - Phytic acid derived bioactive CaO-P2O5-SiO2 gel-glasses. AB - The possibility of using phytic acid as a precursor to synthesize CaO-P(2)O(5) SiO(2) glasses by sol-gel method has been explored and the pseudo ternary phase diagram has been established. It was shown that gel-glasses over a broader range of compositions could be prepared compared to other phosphorus precursors or melt quenching method. Furthermore, phytic acid was found to assist calcium being incorporated into glass networks. In vitro tests in simulated body fluid (SBF) were performed on the above gel-glasses and it was found that they were bioactive over a much broader compositional range especially at high phosphate content, thus enabling one to design bioactive materials with various degradation rates by adjusting the phosphate content. PMID- 22042460 TI - Fabrication of novel biofibers by coating silk fibroin with chitosan impregnated with silver nanoparticles. AB - Nanoparticle based agents often applied as coatings on biomaterials have shown promise in delivering the improved sterility against variety of microbes. In the present study, silk fibers (SF) were coated with chitosan impregnated with silver nanoparticles (Ag-C-SF). These Ag-C-SF fibers were characterized using scanning electron microscopy (SEM) with energy dispersive X-ray analysis, atomic force microscopy (AFM), Infra Red spectroscopy, Thermogravimetric Analysis and Microbiological assay techniques. AFM studies have confirmed the nano sized silver particles in chitosan solution; SEM pictures have exhibited the coating of chitosan along with silver nanoparticles on the silk fibroin. The modified fibers have also shown anti-microbial activity and improved thermal stability. The Ag-C SF fibers may be explored as wound dressing and tendon reconstruction material in future. PMID- 22042462 TI - Fabrication of nano-macroporous glass-ceramic bioscaffold with a water soluble pore former. AB - Recently, several methods have been reported for fabricating tailored amorphous multi porosity bioscaffolds for bone regeneration and tissue engineering. In particular, the melt-quench-heat-etch method appears attractive for making large and/or complex shape structures or fibers for flexible products. However, often the macropore size has been limited to <100 MUm. In this paper we report an improved method for fabricating nano-macroporous soda lime phosphosilicate glass using sucrose as a macropore former. The composite compact consisting of soda lime phosphosilicate glass and sucrose powders is pressed in a die at room temperature. 3D interconnected macroporous structure is formed first by dissolving the sucrose part in water at room temperature, and then sintering the compact at temperatures above the glass transition temperature. Thus, interconnected macropores with controlled size (>=100 microns) are formed readily. The sintering heat-treatment also induces nanoscale phase separation, which is then exploited for introducing nanoscale porosity. For the latter goal, the sample is leached in HCl under optimized conditions to yield desired nano macroporous glass for bone scaffold or other applications. PMID- 22042463 TI - Acute toxicity of high dosage carboxymethyl chitosan and its effect on the blood parameters in rats. AB - This experiment was aimed to study whether Carboxymethyl chitosan has acute toxicity and effects on the blood parameters of rats, which were treated with high dosage carboxymethyl chitosan (1350 mg/kg) through a laparotomy. Acute toxicity was first studied and then kinds of blood parameters were detected at different time points after the laparotomy, which contain coagulant parameters (thrombin time, prothrombin time, activated partial thromboplatin time and fibrinogen), anticoagulant parameter (antithrombin III), fibrinolytic parameters (plasminogen and fibrin degradation product) and hemorheology parameters (blood viscosity). Results showed that no acute toxicity was detected and no significant effects were found on the parameters of coagulation, anticoagulation, fibrinolysis or hemorheology of rats after the laparotomy, which indicated that carboxymethyl chitosan has no significant toxicity on the blood system of rats after being absorbed in the abdominal cavity and degraded gradually in the blood. And this study has provided experimental basis for carboxymethyl chitosan to be applied in the field of biomedical materials. PMID- 22042464 TI - Fabrication and in vivo osteogenesis of biomimetic poly(propylene carbonate) scaffold with nanofibrous chitosan network in macropores for bone tissue engineering. AB - A biomimetic poly(propylene carbonate) (PPC) porous scaffold with nanofibrous chitosan network within macropores (PPC/CSNFs) for bone tissue engineering was fabricated by a dual solid-liquid phase separation technique. PPC scaffold with interconnected solid pore wall structure was prepared by the first phase separation, which showed a high porosity of 91.9% and a good compressive modulus of 14.2 +/- 0.56 MPa, respectively. By the second phase separation, nanofibrous chitosan of 50-500 nm in diameter was formed in the macropores with little influence on the pore structure and the mechanical properties of PPC scaffold. The nanofibrous chitosan content was calculated to be 9.78% by elemental analysis. After incubation in SBF for 14 days, more apatite crystals were deposited on the pore surface as well as the nanofibrous chitosan surface of PPC/CSNFs scaffold compared with PPC scaffold. The in vitro culture of bone mesenchymal stem cells showed that PPC/CSNFs scaffold exhibited a better cell viability than PPC scaffold. After implantation in rabbits for 16 weeks, the defect was entirely repaired by PPC/CSNFs scaffold, as opposed to the incomplete healing for PPC scaffold. It indicated that PPC/CSNFs scaffold showed a faster in vivo osteogenesis rate than PPC scaffold. Hereby, PPC/CSNFs scaffold will be a potential candidate for bone tissue engineering. PMID- 22042465 TI - To be or not to be a general surgeon! PMID- 22042466 TI - A prognostic score to predict major complications after pancreaticoduodenectomy. AB - OBJECTIVE: To develop and validate a simple prognostic score to predict major postoperative complications after pancreaticoduodenectomy (PD). BACKGROUND: PD still carries a high rate of severe postoperative complications. No specific score is currently available to stratify the patient's risk of major morbidity. METHODS: Between 2002 and 2010, preoperative, intraoperative, and outcome data from 700 consecutive patients undergoing PD in our institution were prospectively collected in an electronic database. Major complications were defined as levels III to V of Clavien-Dindo classification. On the basis of a multivariate regression model, the score was developed using a random two-thirds of the population (n = 469) and was validated on the remaining 231 patients. RESULTS: Major complication rate was 16.7% (117/700). Significant predictors included in the scoring system were: pancreas texture, pancreatic duct diameter, operative blood loss, and ASA score. The mean risk of developing major postoperative complications was 7% in patients with score 0 to 3, 13% in patients with score 4 to 7, 23% in patients with score 8 to 11, and 36% in patients with score 12 to 15. In the validation population, the predicted risk of major complications was 15.2% versus a 16.9% observed risk (C-statistic index = 0.743). CONCLUSION: This new score may accurately predict a patient's postoperative outcome. Early identification of high-risk patients could help the surgeon to adopt intraoperative and postoperative strategies tailored on individual basis. PMID- 22042467 TI - Biliary complications after liver transplantation using grafts from donors after cardiac death: results from a matched control study in a single large volume center. AB - OBJECTIVE: To assess the incidence and impact of biliary complications in recipients transplanted from donors after cardiac death (DCD) at one single large institution. BACKGROUND: Shortage of available cadaveric organs is a significant limiting factor in liver transplantation (LT). The use of DCD offers the potential to increase the organ pool. However, early results with DCD liver grafts were associated with a greater incidence of ischemic cholangiopathy (IC), leading to several programs to abandoning this source of organs. METHODS: A retrospective analysis of a prospective database from April 2001 to 2010 focused on 167 consecutive DCD-LT. Each DCD transplant was matched with 2 brain death donors (DBD) grafts (n = 333) according to the period of transplantation. Primary outcome measures were biliary complications including the severity of complications, graft survival and patient survival. Minimum follow-up was 3 months. RESULTS: Anastomotic stricture was the most common biliary complication (DCD = 30, 19% vs. DBD = 41, 13%). Most were treated endocoscopically (grade IIIa = 72%), whereas hepatico-jejunostomy (grade IIIb) was performed in 22%. Primary IC occurred in 4 (2.5%) recipients from the DCD group and was absent in the DBD group (P = 0.005). However, none of these patients required retransplantation. Patient and graft survival at 1, 3, and 5 years were similar between DCD and DBD groups (P = 0.106, P = 0.138, P = 0.113, respectively). CONCLUSIONS: The encouraging results with DCD-LT are probably due to the selection of DCD grafts and clear definition of warm ischemia. PMID- 22042468 TI - Are there better guidelines for allocation in liver transplantation? A novel score targeting justice and utility in the model for end-stage liver disease era. AB - OBJECTIVES: To design a new score on risk assessment for orthotopic liver transplantation (OLT) based on both donor and recipient parameters. BACKGROUND: The balance of waiting list mortality and posttransplant outcome remains a difficult task in the era of the model for end-stage liver disease (MELD). METHODS: Using the United Network for Organ Sharing database, a risk analysis was performed in adult recipients of OLT in the United States of America between 2002 and 2010 (n = 37,255). Living donor-, partial-, or combined-, and donation after cardiac death liver transplants were excluded. Next, a risk score was calculated (balance of risk score, BAR score) on the basis of logistic regression factors, and validated using our own OLT database (n = 233). Finally, the new score was compared with other prediction systems including donor risk index, survival outcome following liver transplantation, donor-age combined with MELD, and MELD score alone. RESULTS: Six strongest predictors of posttransplant survival were identified: recipient MELD score, cold ischemia time, recipient age, donor age, previous OLT, and life support dependence prior to transplant. The new balance of risk score stratified recipients best in terms of patient survival in the United Network for Organ Sharing data, as in our European population. CONCLUSIONS: The BAR system provides a new, simple and reliable tool to detect unfavorable combinations of donor and recipient factors, and is readily available before decision making of accepting or not an organ for a specific recipient. This score may offer great potential for better justice and utility, as it revealed to be superior to recent developed other prediction scores. PMID- 22042469 TI - Selective targeting of genetically engineered mesenchymal stem cells to tumor stroma microenvironments using tissue-specific suicide gene expression suppresses growth of hepatocellular carcinoma. AB - BACKGROUND: The use of engineered mesenchymal stem cells (MSCs) as therapeutic vehicles for the treatment of experimental pancreatic and breast cancer has been previously demonstrated. The potential application of MSCs for the treatment of hepatocellular carcinoma (HCC) has been controversial. The general approach uses engineered MSCs to target different aspects of tumor biology, including angiogenesis or the fibroblast-like stromal compartment, through the use of tissue-specific expression of therapeutic transgenes. The aim of the present study was (1) to evaluate the effect of exogenously added MSCs on the growth of HCC and (2) the establishment of an MSC-based suicide gene therapy for experimental HCC. METHODS: Mesenchymal stem cells were isolated from bone marrow of C57/Bl6 p53(-/-) mice. The cells were injected into mice with HCC xenografts and the effect on tumor proliferation and angiogenesis was evaluated. The cells were then stably transfected with red fluorescent protein (RFP) or Herpes simplex virus thymidine kinase (HSV-Tk) gene under control of the Tie2 promoter/enhancer or the CCL5 promoter. Mesenchymal stem cells were injected intravenously into mice with orthotopically growing xenografts of HCC and treated with ganciclovir (GCV). RESULTS: Ex vivo examination of hepatic tumors revealed tumor-specific recruitment, enhanced tumor growth, and increased microvessel density after nontherapeutic MSC injections. After their homing to the hepatic xenografts, engineered MSCs demonstrated activation of the Tie2 or CCL5 promoter as shown by RFP expression. Application of CCL5/HSV-TK transfected MSCs in combination with GCV significantly reduced tumor growth by 56.4% as compared with the control group and by 71.6% as compared with nontherapeutic MSC injections. CCL5/HSV-TK(+) transfected MSCs proved more potent in tumor inhibition as compared with Tie2/HSV TK(+) MSCs. CONCLUSION: Exogenously added MSCs are recruited to growing HCC xenografts with concomitant activation of the CCL5 or Tie2 promoters within the MSCs. Stem cell-mediated introduction of suicide genes into the tumor followed by prodrug administration was effective for treatment of experimental HCC and thus may help fill the existing gap in bridging therapies for patients suffering from advanced HCCs. PMID- 22042470 TI - Additional resection of an intraoperative margin-positive proximal bile duct improves survival in patients with hilar cholangiocarcinoma. AB - OBJECTIVE: To assess the survival benefit of additional resection of an intraoperative positive proximal bile duct margin (BD(Marg)) in patients undergoing hepatectomy for hilar cholangiocarcinoma (HCCA). SUMMARY BACKGROUND DATA: Intraoperative evidence of invasive cancer at the proximal (BD(Marg)) is associated with a dismal survival irrespective of whether a final negative (BD(Marg)) is achieved with an additional resection. METHODS: Clinicopathologic, operative, and survival data of consecutive patients undergone curative intent hepatectomy with bile duct resection (n = 75) for HCC (1989-2010) were analyzed. RESULTS: Frozen-section examination of the proximal (BD(Marg)) revealed invasive cancer in 19 of the 67 patients. After additional resection, which was possible in 18 cases, a secondary R0 (BD(Marg)) resection was achieved in 15 patients (83.3%), with 2 of these having, at final pathology, positive radial and distal margins. Eventually, 8 patients were classified as R1 and 67 as R0 (54 primary R0 and 13 secondary R0). Median survival of patients who had a secondary R0 resection (30.6 months) was similar to that of primarily R0-resected patients (29.3 months) and significantly better than that of R1 patients (14.9 months) (P = 0.026). Median time to recurrence and site of recurrence were similar in R0 patients independently of the performance of an additional resection. The incidence of biliary fistula was significantly increased (44.4% vs 17.5%; P = 0.02) in patients necessitating a margin re-resection. CONCLUSIONS: Additional resection of a positive proximal (BD(Marg)) , albeit associated with an increased risk of biliary fistula, offers a significant survival benefit and should be attempted whenever possible. PMID- 22042471 TI - Prediction of prognosis is not improved by the seventh and latest edition of the TNM classification for colorectal cancer in a single-center collective. AB - OBJECTIVES: To compare the prognostic value of the sixth and seventh editions of the TNM classification, and of additional prognostic factors, in colorectal cancer. BACKGROUND: The seventh TNM edition was released in 2009 with the aim of providing a more precise prediction of prognosis. METHODS: Clinical and histopathological data of 2229 patients with colorectal cancer who underwent tumor resection between 1990 and 2006 were analyzed and compared by using the sixth and seventh editions of the TNM classification and a statistically calculated model of prognostic factors. RESULTS: With the sixth edition, 5-year survival was 96% for stage I, 90% for IIA, 86% for IIB, 90% for IIIA, 72% for IIIB, 48% for IIIC, and 13% for IV. With the seventh edition, 5-year survival was 96% for stage I, 90% for IIA, 84% for IIB, 87% for IIC, 89% for IIIA, 72% for IIIB, 36% for IIIC, 15% for IVA, and 10% for IVB. The stage shifted for only 155 (7%) patients: from IIB to IIC (2%), from IIIB to IIIC (1%), and from IIIC to IIIA/B (4%). The performance of the seventh edition [concordance index (c-index) 0.83; 95% confidence interval (CI), 0.82-0.85] revealed no relevant improvement compared with the sixth edition (c-index 0.83; 95% CI, 0.82-0.84), or compared to a model based on independent prognostic factors (c-index 0.84; 95% CI, 0.83 0.86). CONCLUSIONS: The seventh TNM edition did not provide greater accuracy in predicting colorectal cancer patients' prognosis but resulted in a more complex classification for daily clinical use. PMID- 22042472 TI - Prognostic impact of upper, middle, and lower third mucosal or submucosal infiltration in early esophageal cancer. AB - OBJECTIVE: To identify differences in survival of patients with pT1 esophageal cancer relating to depth of wall infiltration. BACKGROUND DATA: Histologic analysis of mucosal and submucosal infiltration in thirds has shown an increasing rate of lymph node metastases (LNM) according to the depth of wall infiltration in pT1 esophageal cancer. METHODS: One hundred seventy-one patients had transthoracic en bloc (n = 161) or transhiatal esophagectomy (n = 10) for pT1 esophageal cancer [121 adenocarcinomas (AC), 50 squamous cell carcinomas (SCC)]. The histologic analysis of the specimen comprised depth of wall penetration of the carcinoma in thirds of pT1a = mucosa (m1, m2, m3) or pT1b = submucosa (sm1, sm2, sm3) and number and infiltration of the resected lymph nodes. RESULTS: The rate of LNM was 0% for 70 mucosal carcinomas and 34% for 101 submucosal carcinomas (P = 0.001). For sm1, this rate was 13%, for sm2 19% and for sm3 56%. The 5-year survival rate (5Y-SR) was 82% for pN0 and 45% for pN+ patients (P < 0.001). There was no significant prognostic difference between AC and SCC (5Y-SR: 74% vs 71%). The 5Y-SR of the pT1a group was 87% compared with 66% for pT1b (P = 0.046). The 5-year survival rate for sm1 and sm2 were similar; sm1 + sm2 were together significantly better (80%) than sm3 (46%) (P = 0.008). In multivariate analysis, only sm3 was an independent prognostic factor (P = 0.01). CONCLUSIONS: After esophagectomy, the prognosis of patients with sm1/sm2 infiltration is as good as for patients with mucosal carcinoma. Sm3 infiltration is the worst prognostic factor in pT1 esophageal cancer. PMID- 22042473 TI - Hedgehog inhibition with the orally bioavailable Smo antagonist LDE225 represses tumor growth and prolongs survival in a transgenic mouse model of islet cell neoplasms. AB - BACKGROUND: This study was designed to evaluate the role of the hedgehog pathway in tumor progression of murine islet cell tumors. Blockade of aberrant hedgehog activation has recently been proposed as a therapeutic target, but effects in models of islet cell tumors with a new orally bioavailable Smoothened (Smo) antagonist LDE225 have not been examined. MATERIAL AND METHODS: To assess in vivo effects, transgenic Rip1Tag2 mice, which develop islet cell neoplasms, were treated with vehicle or LDE225 (80 mg/kg/d) from week 5 until death. The resected pancreata were evaluated macroscopically and microscopically by iummohistochemsistry. Quantitative real-time polymerase chain reaction was performed for hedgehog target genes with RNA from islet, isolated from treated and untreated Rip1Tag2 mice. RESULTS: LDE225 significantly reduced tumor volume by 95% compared with untreated control mice. Hedgehog inhibition with LDE225 significantly prolonged median survival in the used transgenic mouse model (105 vs 116 days; P = 0.02). Quantitative real-time polymerase chain reaction for downstream hedgehog target genes demonstrated significant downregulation in the islet cell tumors of Rip1Tag2 mice treated with LDE225, confirming the ability to achieve effective pharmacologic levels of LDE225 within the desired tissue site, in vivo. CONCLUSION: This is the first study to show that the orally bioavailable Smo antagonist LDE225 may provide a new option for therapy of islet cell neoplasms. PMID- 22042474 TI - Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group. AB - OBJECTIVE: Define the optimal surgical margin in patients undergoing surgery for intrahepatic cholangiocarcinoma (IHCC). BACKGROUND DATA: Surgery is the most effective treatment for IHCC. However, the influence of R1 resection on outcome is controversial and that of margin width has not been evaluated. METHODS: We studied 212 patients undergoing curative resection of mass-forming-type IHCC. The respective influences on survival of resection status (R0 vs R1), surgical margin width, pTNM stage, and the latter's components were evaluated. RESULTS: Incidence of R1 resection was 24%. Overall, R1 resection was not an independent predictor of survival [odds ratio (OR) 1.2 (0.7-2.1)] in contrast to the pTNM stage [OR 2.10 (1.2-3.5)]. In the 78 pN+ patients, survival was similar after R0 and R1 resections (median: 18 vs 13 months, respectively, P = 0.1). In the 134 pN0 patients, R1 resection was an independent predictor of poor survival [OR 9.6 (4.5 20.4)], as was the presence of satellite nodules [OR 1.9 (1.1-3.2)]. In the 116 pN0 patients with R0 resections, median survival was correlated with margin width (<=1 mm: 15 months; 2-4 mm: 36 months; 5-9 mm: 57 month; >=10 mm: 64 month, P < 0.001) and a margin >5 mm was an independent predictor of survival [OR 2.22 (1.59 3.09)]. CONCLUSION: Patients undergoing surgery for IHCC are at high risk of R1 resections. In pN0 patients, R1 resection is the strongest independent predictor of poor outcome and a margin of at least 5 mm should be created. The survival benefits of resection in pN+ patients and R1 resection in general are very low. PMID- 22042478 TI - Is retrieval of >25 lymph nodes a superior criterion for locally advanced gastric cancer surgery? PMID- 22042479 TI - Inpatient insulin orders: are patients getting what is prescribed? AB - BACKGROUND: In-hospital insulin administration is associated with many medication errors, but the frequency and reasons for insulin administration errors are poorly described. To document types and frequency of errors related to insulin administration, an examination of 4 units was conducted. METHODS: Using snapshot methodology, 4 non-intensive care unit (ICU) areas (medicine, cardiology, transplant, and surgery) were examined in an observational, prospective manner for 4 weeks. Each patient on insulin on the first day was followed for 7 days. Definitions and error categories were defined prior to data collection. Error types and numbers were collected and quantified on per-day or per-patient basis. RESULTS: A total of 116 patient audit periods covering a total of 378 inpatient hospital days were examined. Inpatient insulin regimens on day 1 included correctional insulin only (51.7% of cases), neutral protamine Hagedorn ([NPH] 12%), and glargine (28.4%). A total of 199 administration errors occurred at a rate of 1.72 errors/patient-period and 0.53 errors/patient day. Missing documentation of doses (15.5% of all patients) and insulin being held without an order (25% of patients) were the most frequently occurring events. Other errors include transcription (7.5%), timing errors (22.7%), and lack of documentation of physician notification of hypoglycemia (12.6%). CONCLUSIONS: Errors associated with insulin in the hospital are common and reveal a number of system errors that should be addressed. These data provide a foundation for future performance improvement. PMID- 22042480 TI - Eicosanoids and other lipid mediators and the tumor hypoxic microenvironment. AB - Hypoxia is a pathological hallmark feature of solid tumors. Though hypoxia is an adverse physiological state, tumors have evolved to utilize this unsuitable environment to their own advantage by activating key biochemical and cellular pathways that are important in progression, survival, and metastasis. Several studies have emphasized the importance of lipid mediators in regulating key biomolecules in the hypoxic microenvironment, for example hypoxia inducible factor-1 (HIF-1), the master regulator of hypoxia. Lipid mediators have been reported to enhance the levels and activity of HIF-1, which subsequently signal to stimulate angiogenesis and tumor cell survival under hypoxic conditions. There are also reports of hypoxia and HIF-1 enhancing the levels of some lipid mediators mostly by upregulating the levels of the enzymes responsible for their biosynthesis. This review gives a brief overview of these two mechanisms and the role played by bioactive lipid mediators in the regulation of tumor progression and survival under hypoxia. PMID- 22042481 TI - Analysis of gene expression profiles of two near-isogenic lines differing at a QTL region affecting oil content at high temperatures during seed maturation in oilseed rape (Brassica napus L.). AB - Seed oil production in oilseed rape is greatly affected by the temperature during seed maturation. However, the molecular mechanism of the interaction between genotype and temperature in seed maturation remains largely unknown. We developed two near-isogenic lines (NIL-9 and NIL-1), differing mainly at a QTL region influencing oil content on Brassica napus chromosome C2 (qOC.C2.2) under high temperature during seed maturation. The NILs were treated under different temperatures in a growth chamber after flowering. RNA from developing seeds was extracted on the 25th day after flowering (DAF), and transcriptomes were determined by microarray analysis. Statistical analysis indicated that genotype, temperature, and the interaction between genotype and temperature (G * T) all significantly affected the expression of the genes in the 25 DAF seeds, resulting in 4,982, 19,111, and 839 differentially expressed unisequences, respectively. NIL-9 had higher seed oil content than NIL-1 under all of the temperatures in the experiments, especially at high temperatures. A total of 39 genes, among which six are located at qOC.C2.2, were differentially expressed among the NILs regardless of temperature, indicating the core genetic divergence that was unaffected by temperature. Increasing the temperature caused a reduction in seed oil content that was accompanied by the downregulation of a number of genes associated with red light response, photosynthesis, response to gibberellic acid stimulus, and translational elongation, as well as several genes of importance in the lipid metabolism pathway. These results contribute to our knowledge of the molecular nature of QTLs and the interaction between genotype and temperature. PMID- 22042482 TI - QTL mapping under truncation selection in homozygous lines derived from biparental crosses. AB - In plant breeding, a large number of progenies that will be discarded later in the breeding process must be phenotyped and marker genotyped for conducting QTL analysis. In many cases, phenotypic preselection of lines could be useful. However, in QTL analyses even moderate preselection can have a significant effect on the power of QTL detection and estimation of effects of the target traits. In this study, we provide exact formulas for quantifying the change of allele frequencies within marker classes, expectations of marker contrasts and the variance of the marker contrasts under truncation selection, for the general case of two QTL affecting the target trait and a correlated trait. We focused on homozygous lines derived at random from biparental crosses. The effects of linkage between the marker and the QTL under selection as well as the effect of selection on a correlated trait can be quantified with the given formulas. Theoretical results clearly show that depending on the magnitude of QTL effects, high selection intensities can lead to a dramatic reduction in power of QTL detection and that approximations based on the infinitesimal model deviate substantially from exact solutions. The presented formulas are valuable for choosing appropriate selection intensity when performing QTL mapping experiments on the data on phenotypically preselected traits and enable the calculation and bias correction of the effects of QTL under selection. Application of our theory to experimental data revealed that selection-induced bias of QTL effects can be successfully corrected. PMID- 22042483 TI - Divergent synthetic approach to 6''-modified alpha-GalCer analogues. AB - A synthetic approach is presented for the synthesis of galacturonic acid and D fucosyl modified KRN7000. The approach allows for late-stage functionalisation of both the sugar 6''-OH and the sphingosine amino groups, which enables convenient synthesis of promising 6''-modified KRN7000 analogues. PMID- 22042484 TI - The source of leptin, but not leptin depletion in response to food restriction, changes during early pregnancy in mice. AB - Maternal food restriction during pregnancy results in adverse consequences for offspring, including obesity and cardiovascular disease. Early pregnancy is a critical period for this programming effect. Leptin is a regulator of energy homeostasis that also affects placental and fetal development. As food restriction results in decreased serum leptin levels, at least in non-pregnant animals, leptin depletion may be one mechanism by which food restriction affects development. The objective of this study was to test whether moderate food restriction affects serum leptin concentrations during the first half of pregnancy. We found that restriction to 50% of ad libitum consumption levels resulted in a significant decrease in serum leptin concentrations in both pregnant and non-pregnant female mice. There was no significant difference in serum leptin concentrations between non-pregnant females and at pregnancy day 11.5 when fed ad libitum. However, there was a difference in the source of leptin during pregnancy, with greater production in visceral fat in pregnant mice, and greater production in subcutaneous fat in non-pregnant mice. Leptin concentrations were dependent on time of day and time of sampling relative to feeding, particularly in restricted mice. There was a significant difference in serum leptin concentrations between fed and restricted mice when they were fed and sampled in afternoon, but not when they were fed and sampled in morning. We conclude that food restriction results in a significant decrease in leptin concentration during the first half of pregnancy in mice, but that detection of this relationship is subject to experimental design considerations. PMID- 22042485 TI - The association of serum chemerin level with risk of coronary artery disease in Chinese adults. AB - Chemerin is a newly discovered adipokine which has been found closely associated with obesity, metabolic syndrome (MetS), and inflammatory status. This study will investigate whether serum chemerin levels are associated with coronary artery disease (CAD) independently of other cardiovascular risk factors. This study included a total of 430 subjects (239 with CAD and 191 with non-CAD) who underwent coronary angiography. Anthropometric measurements were performed and chemerin, glucose, lipid profiles, and other biochemical characteristics were measured. The severity of coronary atherosclerosis was estimated by the total number of diseased vessels and Gensini score. Serum chemerin levels were significantly higher in the CAD group than in the non-CAD group (P = 0.011). The odds ratios (95% CI) of CAD across increasing quartiles of serum chemerin were 1.04 (0.61-1.78), 1.08 (0.63-1.83), and 1.87 (1.07-3.24), (P = 0.386, 0.508, and 0.012, respectively). Adjusting for age, sex, and other conventional risk factors for CAD did not appreciably alter the results. Serum chemerin levels were significantly increased with an increasing of number of diseased vessels (P = 0.024). In conditional linear regression models, chemerin levels were positively related to Gensini score even after established cardiovascular risk factors (beta = 0.13, P = 0.019). Correlation analysis showed serum chemerin levels were significantly associated with TG levels, TC levels, fasting serum insulin, HOMA IR and MetS (all P < 0.05). Higher serum chemerin levels were associated with increased risk of CAD and metabolic parameters in Chinese adults. Chemerin may represent a novel link between metabolic signals and atherosclerosis. PMID- 22042486 TI - An ontogenic study of adrenomedullin gene expression in the rat lung, adrenal, kidney, and heart. AB - In this study, the gene expression of adrenomedullin (Adm) in the peripheral tissues which include lung, adrenal, kidney, and heart during development was investigated in the rat. The preproadrenomedullin (preproAdm) mRNA and mRNAs of its related receptor components, calcitonin receptor-like receptor (Crlr), and receptor activity-modifying proteins (Ramp1, 2 and 3) of the lung, adrenal, kidney, and heart were measured by real-time RT-PCR and the ADM peptide measured by radioimmunoassay in 1-, 7-, 21-day-old rats and the adult rats. From day 1 to 21, preproAdm mRNA levels increased with age in the lung, the kidney, and the heart but decreased with age in the adrenal. ADM levels, however, increased with age in the lung but decreased with age in the kidney, the adrenal, and the heart. The preproAdm levels in the lung, in the kidney, and in the adrenal all increased in the adult rat. ADM peptide levels, however, decreased in the adult rat. Crlr and Ramp2 gene expression increased with age in the lung, in the kidney, and in the heart but decreased with age in the adrenal in the prepubertal rats. The results indicate that the levels of preproAdm mRNA, ADM peptide and its receptor component mRNAs in different tissues followed different patterns of changes during development. PMID- 22042487 TI - Primary aldosteronism: from bench to bedside. AB - Primary aldosteronism is now thought to be the commonest potentially curable and specifically treatable form of hypertension. The detection of primary aldosteronism is of utmost importance not only because it provides an opportunity for a targeted treatment, but also because it has been demonstrated that patients with primary aldosteronism are more prone to cardiovascular events and target organ damage than essential hypertensives. Normalization of blood pressure and hypokalemia should not be the only goal of treatment. Normalization of circulating aldosterone or mineralocorticoid blockade is necessary to prevent aldosterone-induced tissue damage that occurs independent of blood pressure. This review will focus on the current understanding and comprehensive management review of primary aldosteronism, highlighting the new evidence that has become recently available. PMID- 22042488 TI - Comparative analysis of peptide p5 and serum amyloid P component for imaging AA amyloid in mice using dual-isotope SPECT. AB - PURPOSE: I-labeled human serum amyloid P component (SAP) is used clinically only in the UK for imaging visceral amyloidosis to assist with diagnosis, disease staging, and monitoring response to therapy. We compare a new amyloid-reactive probe, peptide p5, with SAP for imaging amyloidosis. PROCEDURES: Dual-energy SPECT/CT images were acquired of (125)I-labeled SAP and (99m)Tc-labeled p5 in mice with systemic AA amyloidosis (n = 3). Twelve organs and tissues were harvested for radiotracer biodistribution assessment and for micro autoradiographic analysis. RESULTS: I-SAP and (99m)Tc-p5 localized equivalently in amyloid deposits in liver (~10% injected dose (ID)/g) whereas (125)I-SAP was twofold higher in the spleen (~20% ID/g; (99m)Tc-p5, ~10% ID/g). In contrast, (99m)Tc-p5 was bound to pancreatic and intestinal amyloid approximately fivefold more efficiently as evidenced in biodistribution data. CONCLUSIONS: Radiolabeled p5 is an effective amyloid-imaging radiotracer as compared to SAP in the murine model of amyloidosis and may be rapidly translated for imaging patients with visceral amyloidosis in the USA. PMID- 22042489 TI - Synthesis of the first heterometalic star-shaped oxido-bridged MnCu3 complex and its conversion into trinuclear species modulated by pseudohalides (N3(-), NCS- and NCO-): structural analyses and magnetic properties. AB - A tetra-nuclear, star-shaped hetero-metallic copper(II)-manganese(II) complex, [{CuL(H(2)O)}(2)(CuL)Mn](ClO(4))(2) (1) has been synthesized by reacting the "complex as ligand" [CuL] with Mn(ClO(4))(2) where H(2)L is the tetradentate di Schiff base derived from 1,3-propanediamine and 2-hydroxyacetophenone. Upon treatment with the polyatomic anions azide, cyanate, or thiocyanate in methanol medium, complex 1 transforms into the corresponding trinuclear species [(CuL)(2)Mn(N(3))(2)] (2), [(CuL)(2)Mn(NCO)(2)] (3) and [(CuL)(2)Mn(NCS)(2)] (4). All four complexes have been structurally and magnetically characterized. In complex 1 the central Mn(II) ion is encapsulated by three terminal [CuL] units through the formation of double phenoxido bridges between Mn(II) and each Cu(II). In complexes 2-4 one of the CuL units is replaced by a couple of terminal azide, N-bonded cyanate or N-bonded thiocyanate ions respectively and the central Mn(II) ion is connected to two terminal Cu(II) ions through a double asymmetric phenoxido bridge. Variable temperature magnetic susceptibility measurements show the presence of moderate ferrimagnetic exchange interactions in all the cases mediated through the double phenoxido bridges with J values (H = -JS(i)S(i + 1)) of -41.2, -39.8 and -12.6 cm(-1) (or -40.5 and -12.7 cm(-1) if we use a model with two different exchange coupling constants) for the tetranuclear MnCu(3) cluster in compound 1 and -20.0, -17.3 and -32.5 cm(-1) for the symmetric trinuclear MnCu(2) compounds 2-4. These ferrimagnetic interactions lead to spin ground states of 1 (5/2 - 3*1/2) for compound 1 and 3/2 (5/2 - 2*1/2) for compounds 2-4. PMID- 22042490 TI - Th17 cells in systemic lupus erythematosus share functional features with Th17 cells from normal bone marrow and peripheral tissues. AB - This study was designed to investigate the functional heterogeneity of human Th17 and how their plasticity shapes the nature of immune cell responses to inflammation and autoimmune diseases, such as systemic lupus erythematosus (SLE). We evaluated functional Th17 cell subsets based on the profile of cytokine production in peripheral blood (PB), bone marrow aspirates (BM) and lymph node biopsies (LN) from healthy individuals (n = 35) and PB from SLE patients (n = 34). Data were analysed by an automated method for merging and calculation of flow cytometric data, allowing us to identify eight Th17 subpopulations. Normal BM presented lower frequencies of Th17 (p = 0.006 and p = 0.05) and lower amount of IL-17 per cell (p = 0.03 and p = 0.02), compared to normal PB and LN biopsies. In the latter tissues were found increased proportions of Th17 producing TNF alpha or TNF-alpha/IL-2 or IFN-gamma/TNF-alpha/IL-2, while in BM, Th17 producing other cytokines than IL-17 was clearly decreased. In SLE patients, the frequency of Th17 was higher than in control, but the levels of IL-17 per cell were significantly reduced (p < 0.05). Among the eight generated subpopulations, despite the great functional heterogeneity of Th17 in SLE, a significant low proportion of Th17 producing TNF-alpha was found in inactive SLE, while active SLE showed a high proportion producing only IL-17. Our findings support the idea that the functional heterogeneity of Th17 cells could depend on the cytokine microenvironment, which is distinct in normal BM as well as in active SLE, probably due to a Th1/Th2 imbalance previously reported by our group. PMID- 22042491 TI - Prevalence of overweight in Moroccan patients with rheumatoid arthritis and its relationships with disease features. AB - We aimed to estimate the prevalence of overweight in Moroccan patients with rheumatoid arthritis (RA) and its relationships with disease activity, functional disability, structural damage, and immunological status. Two hundred fifty patients with RA were consecutively included. Patients' characteristics were specified. The following data were collected: age, disease duration, disease activity (evaluated with physical examination data, biological tests (erythrocyte sedimentation rate and C-reactive protein), and the disease activity score (DAS28)), radiographic changes (assessed by the Sharp's method), functional disability (assessed by using the Health Assessment Questionnaire), extra articular manifestations, immunological status, and treatment details. Overweight was defined according to the body mass index (BMI) values: underweight, <18.5; normal weight, 18.5-24.9; overweight, 25-29.9; and obesity, >=30. The mean age of patients was 46.31 +/- 12.64 years. The mean disease duration was 9.46 +/- 8.43 years. Seventy-five patients (30%) were overweight, 42 (16.8%) were obese, and 133 (53.2%) were normal. Increased BMI was associated with the activity of disease (DAS28) (r = 0.426), structural damage (Sharp total score) (r = 0.297), the rate of rheumatoid factor (r = 0.311), and with the rate of anti-cyclic citrullinated protein antibodies (for all p <= 0.01). There were no statistically significant differences in BMI according to gender, dose and duration of corticosteroids, or functional impairment. In our sample, overweight seems to be prevalent in our RA patients. Overweight seems to occur independently of treatment and shown to be mainly associated to disease activity, structural damage, and immunological status. Large studies are needed to confirm those results. PMID- 22042492 TI - Primary biliary cirrhosis in a rheumatoid arthritis patient treated with rituximab, a case-based review. AB - Primary biliary cirrhosis (PBC) is an autoimmune disease in which intrahepatic bile ducts are targeted by an immune-mediated injury. This disease tends to progress to fibrosis and cirrhosis with hepatic failure. The authors report a case of a 50-year-old rheumatoid arthritis (RA) patient, with erosions and seropositive for rheumatoid factor and anti-citrullinated peptide antibodies, with 18 years disease duration refractory to prednisolone and several disease modifying antirheumatic drugs, either conventional or biological (adalimumab and etanercept). In April 2007, she started therapy with rituximab (RTX) with good European League Against Rheumatism response achieved 9 months later. In June 2008, she was admitted with intrahepatic cholestasis, steatorrhea, and spontaneous fractures of various ribs. After excluding cholelitiasis, as well as infectious and neoplastic diseases a liver biopsy was performed that was compatible with the diagnosis of PBC. The antinuclear antibodies (1/160) were positive as well as the antimitochondrial antibodies (1/640). Other antibodies were negative such as anti-SSA and anti-SSB. Afterwards, the patient started ursodesoxycholic acid 15 mg kg(-1) day(-1) with progressive improvement of cholestatic markers. A labial salivary gland biopsy was performed and showed findings compatible with the concomitant diagnosis of Sjogren's syndrome. Based on this clinical report, a detailed review of the clinical aspects of PBC is presented as well as its association with other immune-mediated inflammatory diseases, particularly, with RA. PMID- 22042493 TI - The relationship between level of processing and hippocampal-cortical functional connectivity during episodic memory formation in humans. AB - New episodic memory traces represent a record of the ongoing neocortical processing engaged during memory formation (encoding). Thus, during encoding, deep (semantic) processing typically establishes more distinctive and retrievable memory traces than does shallow (perceptual) processing, as assessed by later episodic memory tests. By contrast, the hippocampus appears to play a processing independent role in encoding, because hippocampal lesions impair encoding regardless of level of processing. Here, we clarified the neural relationship between processing and encoding by examining hippocampal-cortical connectivity during deep and shallow encoding. Participants studied words during functional magnetic resonance imaging and freely recalled these words after distraction. Deep study processing led to better recall than shallow study processing. For both levels of processing, successful encoding elicited activations of bilateral hippocampus and left prefrontal cortex, and increased functional connectivity between left hippocampus and bilateral medial prefrontal, cingulate and extrastriate cortices. Successful encoding during deep processing was additionally associated with increased functional connectivity between left hippocampus and bilateral ventrolateral prefrontal cortex and right temporoparietal junction. In the shallow encoding condition, on the other hand, pronounced functional connectivity increases were observed between the right hippocampus and the frontoparietal attention network activated during shallow study processing. Our results further specify how the hippocampus coordinates recording of ongoing neocortical activity into long-term memory, and begin to provide a neural explanation for the typical advantage of deep over shallow study processing for later episodic memory. PMID- 22042494 TI - Development of automated detection of radiology reports citing adrenal findings. AB - The aim of this study was to determine the feasibility of automated detection of adrenal nodules, a common finding on CT, using a newly developed search engine that mines dictated radiology reports. To ensure Health Insurance Portability and Accountability Act compliance, we utilized a preexisting de-identified database of 32,974 CT reports from February 1, 2009 to February 28, 2010. Common adrenal descriptors from 29 staff radiologists were used to develop an automated rule based algorithm targeting adrenal findings. Each sentence within the free text of reports was searched with an adapted NegEx negation algorithm. The algorithm was refined using a 2-week test period of reports and subsequently validated using a 6-week period. Manual review of the 3,693 CT reports in the validation period identified 222 positive reports while the algorithm detected 238 positive reports. The algorithm identified one true positive report missed on manual review for a total of 223 true positive reports. This resulted in a precision of 91% (217 of 238) and a recall of 97% (217 of 223). The sensitivity of the query was 97.3% (95% confidence interval (CI), 93.9-98.9%), and the specificity was 99.3% (95% CI, 99.1-99.6%). The positive predictive value of the algorithm was 91.0% (95% CI, 86.6-94.3%), and the negative predictive value was 99.8% (95% CI, 99.6-99.9%). The prevalence of true positive adrenal findings identified by the query (7.1%) was nearly identical to the true prevalence (7.2%). Automated detection of language describing common findings in imaging reports, such as adrenal nodules on CT, is feasible. PMID- 22042495 TI - Temperature mediated generation of armoured bubbles. AB - This communication describes a novel strategy for the continuous microfluidic generation of highly monodispersed particle-coated microbubbles using temperature dependent dissolution of carbon dioxide. PMID- 22042496 TI - Selective CO2 conversion to formate in water using a CZTS photocathode modified with a ruthenium complex polymer. AB - Highly selective photoelectrochemical CO(2) reduction (>80% selectivity) in water was successfully achieved by combining Cu(2)ZnSnS(4) (CZTS) with a metal-complex electrocatalyst. CZTS, a sulfide semiconductor that possesses a narrow band gap and consists of earth-abundant elements, is demonstrated to be a candidate photoabsorber for a CO(2) reduction hybrid photocatalyst. PMID- 22042497 TI - The making of platyrrhine semifolivores: models for the evolution of folivory in primates. AB - Among living New World monkeys, Howlers and Muriquis are by far the most folivorous. We examine how well the morphology and behavior of Alouatta and Brachyteles conform to leaf-eating adaptational models derived from other studies. Both genera match these expectations unevenly, which suggests a broader conception of primate folivory is in order. Hence the notion of "semifolivory." While their dentitions prove highly sensitive to selection for leaf-eating, core features relating to body size, brain size, ranging behavior and presumed energy budgets are less predictable corollaries. Leaf-eating in atelines and colobines may have evolved from a preadaptive reliance on seed-eating, which would have necessitated comparable gastric adaptations. Fossils suggest semifolivory in the low-energy Howler lineage may have begun with an increase in body size, a relatively small brain and, possibly, a concomitantly enlarged gut, followed by dental adaptations. It may have advanced via body-size reduction, part of a pioneering adaptation in marginal ecologies on the periphery of rich Amazonian habitats or as a strategy to minimize competition among an abundance of frugivores within the lowland forest-perhaps not as a fallback scheme. In the high-energy Muriqui, semifolivory may have evolved in more intensely seasonal, low-yield forests where frugivores were constrained and rare, a model more consistent with the fallback paradigm. The seed-to-leaves evolutionary pathway hypothesized for anthropoid leaf-eaters may be a widespread phenomenon in primates. We propose it is ultimately rooted in a pre-euprimate reliance on the seeds and seed coats of primitive angiosperms before the latter evolved attractive sugary fruits to coax primates into becoming dispersers of seeds, instead consumers. PMID- 22042498 TI - Automatic data binning for improved visual diagnosis of pharmacometric models. AB - Visual Predictive Checks (VPC) are graphical tools to help decide whether a given model could have plausibly generated a given set of real data. Typically, time course data is binned into time intervals, then statistics are calculated on the real data and data simulated from the model, and represented graphically for each interval. Poor selection of bins can easily lead to incorrect model diagnosis. We propose an automatic binning strategy that improves reliability of model diagnosis using VPC. It is implemented in version 4 of the MONOLIX: software. PMID- 22042499 TI - Highly efficient aldol additions of DHA and DHAP to N-Cbz-amino aldehydes catalyzed by L-rhamnulose-1-phosphate and L-fuculose-1-phosphate aldolases in aqueous borate buffer. AB - Aldol addition reactions of dihydroxyacetone (DHA) to N-Cbz-amino aldehydes catalyzed by L-rhamnulose-1-phosphate aldolase (RhuA) in the presence of borate buffer are reported. High yields of aldol adduct (e.g. 70-90%) were achieved with excellent (>98 : 2 syn/anti) stereoselectivity for most S or R configured acceptors, which compares favorably to the reactions performed with DHAP. The stereochemical outcome was different and depended on the N-Cbz-amino aldehyde enantiomer: the S acceptors gave the syn (3R,4S) aldol adduct whereas the R ones gave the anti (3R,4R) diastereomer. Moreover, the tactical use of Cbz protecting group allows simple and efficient elimination of borate and excess of DHA by reverse phase column chromatography or even by simple extraction. This, in addition to the use of unphosphorylated donor nucleophile, makes a useful and expedient methodology for the synthesis of structurally diverse iminocyclitols. The performance of aldol additions of dihydroxyacetone phosphate (DHAP) to N-Cbz amino aldehydes using RhuA and L-fuculose-1-phosphate aldolase (FucA) catalyst in borate buffer was also evaluated. For FucA catalysts, including FucA F131A, the initial velocity of the aldol addition reactions using DHAP were between 2 and 10 times faster and the yields between 1.5 and 4 times higher than those in triethanolamine buffer. In this case, the retroaldol velocities measured for some aldol adducts were lower than those without borate buffer indicating some trapping effect that could explain the improvement of yields. PMID- 22042500 TI - Characteristic fragmentation of polysiloxane monolayer films by bombardment with monatomic and polyatomic primary ions in TOF-SIMS. AB - This study reports the characteristic fragmentation patterns from two polysiloxane polymers that form ordered overlayer on silver substrates. Results are compared for the bombardment of various monatomic and polyatomic projectiles of Cs(+), C(60)(+) (10 keV), Bi(1)(+), and Bi(3)(+) (25 keV) in the high mass range time-of-flight secondary ion mass spectrometry (TOF-SIMS) spectra. Results are reported from sub-monolayer (solution cast) coverages of poly(dimethylsiloxane)s with the number average molecular weights (M(n)) of 2200 and 6140 Da, respectively, and Langmuir-Blodgett monolayers of poly(methylphenylsiloxane) with molecular weights (MW) from 600 and 1000 Da. For each film, Bi projectiles resulted in the emission of positive silver cluster ions from the substrate under the polymer overlayer and peaks corresponding to silver cluster ions with larger mass were observed by impact of polyatomic 25 keV Bi(3)(+) projectiles. In addition, depending on the change of energy of Bi (3) (+) , a different pattern of fragments was observed. With Cs(+) and C(60)(+) impact, however, the emission of silver cluster ions was not detected. In the case of C(60)(+) impact for PDMS-6140, peaks corresponding to silver-cationized intact oligomers were not observed. In this paper, these results are explained by the possible bombardment mechanism for each projectile, based on its mass, energy, and split trajectories of the component atoms under the polyatomic impact. PMID- 22042501 TI - Organochlorine pesticide levels in female adipose tissue from Puebla, Mexico. AB - The objective of this study was to determine the levels of organochlorine pesticides HCB, alpha-beta-gamma-HCH, pp'DDE, op'DDT and pp'DDT in adipose tissue of females living in Puebla, Mexico. Organochlorine pesticides were analyzed in 75 abdominal adipose tissue samples taken during 2010 by autopsy at the Forensic Services of Puebla. The results were expressed as mg/kg on fat basis. In analyzed samples the following pesticides were detected: p,p'-DDE in 100% of samples at mean 1.464 mg/kg; p,p'-DDT in 96.0.% of samples at mean 0.105 mg/kg; op'DDT in 89.3% of monitored samples at mean 0.025 mg/kg and beta-HCH in 94.7% of the samples at mean 0.108 mg/kg. To show if organochlorine pesticide levels in monitored female's adipose tissues are age dependant, the group was divided in three ages ranges (13-26, 26-57 and 57-96 years). The mean and median levels of all organochlorine pesticides increase significantly (p < 0.05) from the first to second and from the first to third group. At the same time, the increase of mean and medians levels from the second to third group were not statistically significant (p > 0.05). The present results compared to previous ones from 2008 indicates an increase in the concentrations during the 2010 study, but only the differences for pp'DDE and op'DDT were statistically significant. The 2010 group of females was older compared to the 2008 group. The presence of organochlorine pesticide residues is still observed, indicating uniform and permanent exposure to the pesticides by Puebla inhabitants. PMID- 22042502 TI - Validation of models to estimate the fumigant and larvicidal activity of Eucalyptus essential oils against Aedes aegypti (Diptera: Culicidae). AB - The aim of this work is to validate the pre-existing models that relate the larvicidal and adulticidal activities of the Eucalyptus essential oils on Aedes aegypti. Previous works at our laboratory described that the larvicidal activity of Eucalyptus essential oils can be estimated from the relative concentration of two main components (p-cymene and 1,8-cineole) and that the adulticidal effectiveness can be explained, to a great extent, by the presence of large amounts of the component 1,8-cineole in it. In general, the results show that the higher adulticidal effect of essential oils the lower their larvicidal activity. Fresh leaves was harvested and distilled. Once the essential oil was obtained, the chemical composition was analysed, evaluating the biological activity of 15 species of the genus Eucalyptus (Eucalyptus badjensis Beuzev and Welch, Eucalyptus badjensis * nitens, Eucalyptus benthamii var Benthamii Maiden and Cambage, Eucalyptus benthamii var dorrigoensis Maiden and Cambage, Eucalyptus botryoides Smith, Eucalyptus dalrympleana Maiden, Eucalyptus fastigata Deane and Maiden, Eucalyptus nobilis L.A.S. Johnson and K.D.Hill, Eucalyptus polybractea R. Baker, Eucalyptus radiata ssp radiata Sieber ex Spreng, Eucalyptus resinifera Smith, Eucalyptus robertsonii Blakely, Eucalyptus robusta Smith, Eucalyptus rubida Deane and Maiden, Eucalyptus smithii R. Baker). Essential oils of these plant species were used for the validation of equations from preexistent models, in which observed and estimated values of the biological activity were compared. The regression analysis showed a strong validation of the models, re-stating the trends previously observed. The models were expressed as follows: A, fumigant activity [KT(50(min)) = 10.65-0.076 * 1,8-cineole (%)](p < 0.01; F, 397; R (2), 0.79); B, larval mortality (%)((40 ppm)) = 103.85 + 0.482 * p-cymene (%) - 0.363 * alpha-pinene (%) - 1.07 * 1,8-cineole (%) (p < 0.01; F, 300; R (2), 0.90). These results confirmed the importance of the mayor components in the biological activity of Eucalyptus essential oils on A. aegypti. However, it is worth mentioning that two or three species differ in the data estimated by the models, and these biological activity results coincide with the presence of minor differential components in the essential oils. According to what was previously mentioned, it can be inferred that the model is able to estimate very closely the biological activity of essential oils of Eucalyptus on A. aegypti. PMID- 22042503 TI - Real-time PCR assay targeting the actin gene for the detection of Cryptosporidium parvum in calf fecal samples. AB - Cryptosporidium parvum infection is very important with respect to public health, owing to foodborne and waterborne outbreaks and gastrointestinal illness in immunocompetent and immunocompromised persons. In cattle, infection with this species manifests either as a subclinical disease or with diarrheal illness, which occurs more often in the presence of other infectious agents than when alone. The aim of this study was to develop a real-time polymerase chain reaction (PCR) assay for the detection of C. parvum in calf fecal samples and to compare the results of this assay with those of the method routinely used for the diagnosis of Cryptosporidium spp., nested PCR targeting the 18S rRNA gene. Two hundred and nine fecal samples from calves ranging in age from 1 day to 6 months were examined using real-time PCR specific for the actin gene of C. parvum and by a nested PCR targeting the 18S rRNA gene of Cryptosporidium spp. Using real-time PCR detection, 73.2% (153 out of 209) of the samples were positive for C. parvum, while 56.5% (118 out of 209) of the samples were positive for Cryptosporidium spp. when the nested PCR amplification method was used for the detection. The analytical sensitivity of the real-time PCR was approximately one C. parvum oocyst. There was no significant nonspecific DNA amplification of any of the following species and genotype: Cryptosporidium andersoni, Cryptosporidium baileyi, Cryptosporidium bovis, Cryptosporidium canis, Cryptosporidium galli, Cryptosporidium ryanae, Cryptosporidium serpentis, or avian genotype II. Thus, we conclude that real-time PCR targeting the actin gene is a sensitive and specific method for the detection of C. parvum in calf fecal samples. PMID- 22042504 TI - In vitro and in vivo antiparasitic activity of Azadirachtin against Argulus spp. in Carassius auratus (Linn. 1758). AB - Argulus is one of the most common and predominant ectoparasites which cause serious parasitic disease and is a potent carrier of viruses and bacteria in the ornamental fish industry. In recent years, organic (herbs)-based medicines are widely used to cure the disease, and neem (Sarbaroganibarini) medicine is very popular and effective throughout the world. The present study was conducted to find the effects of Azadirachtin against Argulus spp. on Carassius auratus under in vitro and in vivo conditions. The 96-h median lethal concentration (LC(50)) for Azadirachtin EC 25% against Carassius auratus was found to be 82.115 mg L( 1). The antiparasitic activity test under in vitro and in vivo was evaluated at 1 (T1), 5 (T2), 10 (T3), 15 (T4) and 20 mg L(-1) (T5) to treat Argulus for 3 h and 72 h, respectively. In vitro effect of Azadirachtin solution led to 100% mortality of Argulus at 20 and 15 mg L(-1) for 2.5 and 3 h, respectively. Whereas, under in vivo test, the 100% antiparasitic efficacy of Azadirachtin solution was found at 15 and 20 mg L(-1) for 72 and 48 h, respectively. The EC(50) for 48 h was 20 mg L(-1), and thus, therapeutic index is 4.10. The results provided evidence that Azadirachtin can be used as a potential agent for controlling Argulus. PMID- 22042505 TI - A novel herbal formulation against dengue vector mosquitoes Aedes aegypti and Aedes albopictus. AB - The objective of this study was to develop a herbal formulation to control dengue vector mosquitoes. PONNEEM, a novel herbal formulation prepared using the oils of neem (Azadirachta indica), karanj (Pongamia glabra) and their extracts, was tested for larvicidal, ovicidal and oviposition deterrent activities against Aedes aegypti and Aedes albopictus at 1, 0.5, 0.3 and 0.1 ppm concentrations. Cent percent larvicidal and ovicidal activities were observed at 0.1 ppm in the two mosquito species under laboratory and sunlight-exposed conditions up to 12 months from the date of manufacture. Oviposition deterrent activity of 69.97% and 71.05% was observed at 1 ppm concentration of PONNEEM against A. aegypti and A. albopictus, respectively. Reduction in enzyme levels for alpha-esterase was 0.089 +/- 0.008 and 0.099 +/- 0.140 MUg napthol produced/min/mg larval protein; for beta-esterase, it was 0.004 +/- 0.009 and 0.001 +/- 0.028 MUg napthol produced/min/mg larval protein; for glutathione S-transferase, it was 10.4814 +/- 0.23 and 11.4811 +/- 0.21 MUmol/min/mg larval protein and for total protein, it was 0.177 +/- 0.010 and 0.008 +/- 0.005 mg/individual larva in treated groups of A. aegypti and A. albopictus, respectively. The nontarget organisms such as Gambusia affinis and Diplonychus indicus were not affected. No mortality was observed in control. PONNEEM can be used effectively for the management of human vector mosquitoes. PMID- 22042506 TI - Protective effect of isorhynchophylline against beta-amyloid-induced neurotoxicity in PC12 cells. AB - Beta-amyloid peptide (Abeta), a major protein component of senile plaques, has been considered as a critical cause in the pathogenesis of Alzheimer's disease (AD). Modulation of the Abeta-induced neurotoxicity has emerged as a possible therapeutic approach to ameliorate the onset and progression of AD. The present study aimed to evaluate the protective effect of isorhynchophylline, an oxindole alkaloid isolated from a Chinese herb Uncaria rhynchophylla, on Abeta-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that pretreatment with isorhynchophylline significantly elevated cell viability, decreased the levels of intracellular reactive oxygen species and malondialdehyde, increased the level of glutathione, and stabilized mitochondrial membrane potential in Abeta(25-35)-treated PC12 cells. In addition, isorhynchophylline significantly suppressed the formation of DNA fragmentation and the activity of caspase-3 and moderated the ratio of Bcl-2/Bax. These results indicate that isorhynchophylline exerts a neuroprotective effect against Abeta(25 35)-induced neurotoxicity in PC12 cells, at least in part, via inhibiting oxidative stress and suppressing the mitochondrial pathway of cellular apoptosis. PMID- 22042507 TI - Primary mucinous adenocarcinoma of the bladder: complete response with FOLFOX-4 regimen. PMID- 22042508 TI - Polysomnography reveals unexpectedly high rates of organic sleep disorders in patients with prediagnosed primary insomnia. AB - OBJECTIVE: It is a matter of debate whether patients with primary insomnia require a polysomnographic examination in order to exclude specific sleep disorders such as sleep apnea syndrome (SAS) or periodic limb movements (PLM). Using a prospective design, we investigated the prevalence of organic sleep disorders by means of polysomnography (PSG) in a series of patients who were previously diagnosed with primary insomnia. This diagnosis was based on a clinical exam and an ambulatory monitoring device or previous PSG. METHODS: Seventy-seven women and 16 men (mean age 55.12 +/- 13.21 years) who were admitted for cognitive behavioral therapy for insomnia were evaluated by PSG including cardiorespiratory parameters and tibialis EMG. Among them, 50 patients had undergone a clinical exam by a sleep specialist; in 18 patients, actigraphy or portable monitoring had been performed to exclude SAS or PLM; 25 patients had undergone PSG in another sleep lab previously. RESULTS: In 32 patients (34% of the sample), a PSG revealed a specific sleep disorder (SAS 16; PLMD 11; both 5), resulting in therapeutic consequences for 21 patients (SAS 10; PLMD 9; both 2). SAS and PLM patients were older and SAS patients had a higher body mass index than insomnia patients without additional findings. CONCLUSION: Indications for a PSG should be handled less restrictively in the diagnostic workup of older insomnia patients since they have a higher risk of comorbid sleep disorders even in the absence of the clinical signs of SAS or PLM. PMID- 22042509 TI - NaGe3P3: a new ternary germanium phosphide featuring an unusual [Ge3P7] ring. AB - A new ternary germanium phosphide, NaGe(3)P(3), was obtained for the first time with the use of NaP as the reactive flux. It crystallizes in the orthorhombic space group Pmc2(1). The basic structural unit is an unprecedented [Ge(3)P(7)] ring built from one Ge(P)(4) tetrahedron, one Ge(Ge)(P)(3) tetrahedron and one Ge(Ge)(P)(2) trigonal pyramid with Ge in mixed valences of 4+, 3+ and 1+. The bonding between a tetrahedrally coordinated Ge atom and a trigonal pyramidally coordinated Ge atom (with 4s(2) lone pair of electrons) is observed for the first time in inorganic compounds. These [Ge(3)P(7)] rings are connected with each other to form two-dimensional [Ge(3)P(3)](-) layers separated by Na(+) cations. An optical band gap of 2.06(2) eV was deduced from the diffuse reflectance spectrum. Based on the electronic structure calculation, NaGe(3)P(3) is an indirect gap semiconductor with the Ge 4s, Ge 4p and P 3p orbitals strongly hybridizing around the Fermi level. PMID- 22042510 TI - Carbon dioxide narcosis modifies the patch leaving decision of foraging parasitoids. AB - Gleaning information is a way for foragers to adjust their behavior in order to maximize their fitness. Information decreases the uncertainty about the environment and could help foragers to accurately estimate environmental characteristics. In a patchy resource, information sampled during previous patch visits is efficient only if it is retained in the memory and retrieved upon arrival in a new patch. In this study, we tested whether the braconid Asobara tabida, a parasitoid of Drosophila larvae, retains information gleaned on patch quality in the memory and adjusts its foraging behavior accordingly. Females were anesthetized with CO(2) after leaving a first patch containing a different number of hosts and were allowed to visit a second patch containing only kairomones. CO(2) is known to erase unconsolidated information from the memory. We show that in the absence of a short CO(2) narcosis, females responded according to their previous experience, whereas anesthetized females did not. The anesthetized females stayed a given time in the second patch irrespective of what they encountered before. CO(2) narcosis had no effect on the residence time of the non experienced females in a patch containing hosts or only kairomones in comparison with the non-anesthetized females that had a previous foraging experience. We conclude that CO(2) narcosis erases the effect of the previous patch quality, perhaps due to a memory disruption. Direct information processing is likely to be involved in parasitoid decision making through retention of the information on the previous patch quality into a CO(2) sensitive memory. PMID- 22042511 TI - Interdisciplinary teamwork in hospitals: a review and practical recommendations for improvement. AB - Recognizing the importance of teamwork in hospitals, senior leadership from the American College of Physician Executives (ACPE), the American Hospital Association (AHA), the American Organization of Nurse Executives (AONE), and the Society of Hospital Medicine (SHM) established the High Performance Teams and the Hospital of the Future project. This collaborative learning effort aims to redesign care delivery to provide optimal value to hospitalized patients. With input from members of this initiative, we prepared this report which reviews the literature related to teamwork in hospitals. Teamwork is critically important to provide safe and effective hospital care. Hospitals with high teamwork ratings experience higher patient satisfaction, higher nurse retention, and lower hospital costs. Elements of effective teamwork have been defined and provide a framework for assessment and improvement efforts in hospitals. Measurement of teamwork is essential to understand baseline performance, and to demonstrate the utility of resources invested to enhance it and the subsequent impact on patient care. Interventions designed to improve teamwork in hospitals include localization of physicians, daily goals of care forms and checklists, teamwork training, and interdisciplinary rounds. Though additional research is needed to evaluate the impact on patient outcomes, these interventions consistently result in improved teamwork knowledge, ratings of teamwork climate, and better understanding of patients' plans of care. The optimal approach is implementation of a combination of interventions, with adaptations to fit unique clinical settings and local culture. PMID- 22042513 TI - Non-classical heteroacenes: synthesis and properties of anthra[2,3-c:6,7 c']dithiophene derivatives. AB - A new class of linear heteroacenes, anthra[2,3-c:6,7-c']dithiophenes, containing non-classical (non-Kekule) thiophene in a 22-electron pi-conjugated system have been prepared by electrochemical reduction. The electronic properties have been studied by DFT calculations and spectroelectrochemistry, supporting the formation of a triplet electronic structure. PMID- 22042512 TI - Transcallosal sensorimotor fiber tract structure-function relationships. AB - Recent studies have demonstrated neuroanatomically selective relationships among white matter tract microstructure, physiological function, and task performance. Such findings suggest that the microstructure of transcallosal motor fibers may reflect the capacity for interhemispheric inhibition between the primary motor cortices, although full characterization of the transcallosal inhibitory sensorimotor network is lacking. Thus, the goal of this study was to provide a comprehensive description of transcallosal fibers connecting homologous sensorimotor cortical regions and to identify the relationship(s) between fiber tract microstructure and interhemispheric inhibition during voluntary cortical activity. To this end, we assessed microstructure of fiber tracts connecting homologous sensorimotor regions of the cortex with diffusion tensor imaging. We also assessed interhemispheric inhibition by eliciting the ipsilateral silent period (iSP) within the same participants. We mapped mutually exclusive transcallosal connections between homologous sensorimotor regions and computed quantitative metrics of each fiber tract. Paralleling work in non-human primates, we found the densest interhemispheric sensorimotor connections to be between the medial motor areas. Additionally, we provide a midsagittal callosal atlas in normalized Montreal Neurological Institute (MNI) space for future studies to use when investigating callosal fiber tracts connecting primary and secondary sensorimotor cortices. Finally, we report a strong, positive relationship (r = 0.76) between strength of interhemispheric inhibition (iSP) and microstructure of interhemispheric fibers that is specific to tracts connecting the primary motor cortices. Thus, increased fiber microstructure in young adults predicts interhemispheric inhibitory capacity. PMID- 22042514 TI - Pharmacokinetic and pharmacodynamic study on amrubicin and amrubicinol in Japanese patients with lung cancer. AB - PURPOSE: The pharmacokinetic (PK)-pharmacodynamic (PD) relationship of amrubicin and its active metabolite, amrubicinol, has only been evaluated using trough levels of these agents since the full PK profiles not yet been clarified so far. This study was performed to analyze the full PK profiles of amrubicin and amrubicinol and to evaluate their toxicity-PK relationships in Japanese patients. METHODS: Amrubicin (35-40 mg/m(2)) was administered to 21 lung cancer patients on days 1-3 every 3-4 weeks. Fourteen blood samples were obtained per patient over the course of 3 administration days. The plasma concentrations of amrubicin and amrubicinol were quantitated by HPLC, and the relationships between PK parameters of these compounds and hematological toxicities were evaluated. RESULTS: The overall PK profiles of amrubicin and amrubicinol were well characterized using a 3-compartment model and a 1-compartment model with a first-order metabolic process, respectively. The major toxicities were hematological. The clearance of amrubicinol was significantly correlated with grade 4 neutropenia (P = 0.01). The percentage decreases in the neutrophil count, hemoglobin level and platelet count were well correlated with the amrubicinol AUC. CONCLUSION: The pharmacokinetic profiles of amrubicin and amrubicinol were clarified, and the subsequent PK-PD analyses indicate that the clearance of amrubicinol is the major determinant of neutropenia. PMID- 22042515 TI - A systematic approach to the management of patients with brain metastases of known or unknown primary site. AB - PURPOSE: To establish an empirical systematic approach for the management of brain metastases from a variety of cancers. METHODS: The English literature was reviewed from 2000 to 2011 and all clinical trials (phase II, phase III and retrospective studies) regarding therapy of brain metastases were selected for more detailed review. Some key articles published prior to 2000 were also included in the review as are supplemental recommendations based on our clinical experience. RESULTS: Patients with brain metastases from small cell lung cancer (SCLC) at the initial cancer diagnosis can be treated with concomitant whole brain radiation therapy (WBRT) and chemotherapy or first with chemotherapy followed by WBRT. In all other cases, brain metastases are currently treated independently of the management of the extracranial disease with surgery or radiosurgery followed by WBRT. In radioresistant tumors (melanoma, sarcoma, renal cell carcinoma), WBRT may be omitted initially but administered at recurrence. Where surgery or radiosurgery is not an option for patients, WBRT should be administered. Prophylactic WBRT should be given in patients with SCLC and considered in patients with non-small cell lung cancer. Apart from its use in SCLC, chemotherapy for the treatment of brain metastases is reserved for patients enrolled in clinical trials. CONCLUSION: Brain metastases should be treated aggressively and independently of the primary site tumor especially if the performance status of the patient is good. The role of chemotherapy should be addressed in the context of clinical trials. PMID- 22042518 TI - Evolutionary morphology, platyrrhine evolution, and systematics. AB - This special volume of the Anatomical Record focuses on the evolutionary morphology of New World monkeys. The studies range from three-dimensional surface geometry of teeth to enamel ultrastructure; from cranioskeletal adaptations for eating leaves and seeds to the histology of taste bud proxies; from the architecture of its bones to the mechanoreceptors of the tail's skin; from the physical properties of wild foods to the feeding biomechanics of jaws and skull; from the shapes of claws and fingertips, and of elbows, to the diversity and morphology of positional behavior; from the vomeronasal organ and its biological roles to links between brains, guts, sociality, and feeding; from the gum-eating adaptations of the smallest platyrrhines to the methods used to infer how big the largest fossil platyrrhines were. They demonstrate the power of combining functional morphology, behavior, and phylogenetic thinking as an approach toward reconstructing the evolutionary history of platyrrhine primates. While contributing new findings pertaining to all the major clades and ecological guilds, these articles reinforce the view that platyrrhines are a coherent ecophylogenetic array that differentiated along niche dimensions definable principally by body size, positional behavior, and feeding strategies. In underlining the value of character analysis and derived morphological and behavioral patterns as tools for deciphering phylogenetic and adaptational history, doubts are raised about a competing small-bore morphological method, parsimony-based cladistic studies. Intentionally designed not to enlist the rich reservoir of platyrrhine evolutionary morphology, an empirical assessment of the costs incurred by this research stratagem reveals inconsistent, nonrepeatable, and often conflicting results. PMID- 22042516 TI - Prediction of ketoacyl synthase family using reduced amino acid alphabets. AB - Ketoacyl synthases are enzymes involved in fatty acid synthesis and can be classified into five families based on primary sequence similarity. Different families have different catalytic mechanisms. Developing cost-effective computational models to identify the family of ketoacyl synthases will be helpful for enzyme engineering and in knowing individual enzymes' catalytic mechanisms. In this work, a support vector machine-based method was developed to predict ketoacyl synthase family using the n-peptide composition of reduced amino acid alphabets. In jackknife cross-validation, the model based on the 2-peptide composition of a reduced amino acid alphabet of size 13 yielded the best overall accuracy of 96.44% with average accuracy of 93.36%, which is superior to other state-of-the-art methods. This result suggests that the information provided by n peptide compositions of reduced amino acid alphabets provides efficient means for enzyme family classification and that the proposed model can be efficiently used for ketoacyl synthase family annotation. PMID- 22042517 TI - Recombinatorial biosynthesis of polyketides. AB - Modular polyketide synthases (PKSs) from Streptomyces and related genera of bacteria produce many important pharmaceuticals. A program called CompGen was developed to carry out in silico homologous recombination between gene clusters encoding PKSs and determine whether recombinants have cluster architectures compatible with the production of polyketides. The chemical structure of recombinant polyketides was also predicted. In silico recombination was carried out for 47 well-characterised clusters. The predicted recombinants would produce 11,796 different polyketide structures. The molecular weights and average degree of reduction of the chemical structures are dispersed around the parental structures indicating that they are likely to include pharmaceutically interesting compounds. The details of the recombinants and the chemical structures were entered in a database called r-CSDB. The virtual compound library is a useful resource for computer-aided drug design and chemoinformatics strategies for finding pharmaceutically relevant chemical entities. A strategy to construct recombinant Streptomyces strains to produce these polyketides is described and the critical steps of mobilizing large biosynthetic clusters and producing new linear cloning vectors are illustrated by experimental data. PMID- 22042519 TI - A new practical synthesis of triaryl and trisindolylmethanes under solvent-free reaction conditions. AB - An efficient and practical synthesis of triaryl and trisindolylmethanes is reported via the bisarylation of aryl aldehydes with activated arenes. The new method features mild solvent-free reaction conditions, in most cases nearly stoichiometric reagent ratios, catalytic amount of the readily available, easily handled, recoverable and reusable Bronsted acid catalyst o-benzenedisulfonimide. PMID- 22042520 TI - Effect of changes over time in the performance of a customized SAPS-II model on the quality of care assessment. AB - PURPOSE: The aim of our study was to explore, using an innovative method, the effect of temporal changes in the mortality prediction performance of an existing model on the quality of care assessment. The prognostic model (rSAPS-II) was a recalibrated Simplified Acute Physiology Score-II model developed for very elderly Intensive Care Unit (ICU) patients. METHODS: The study population comprised all 12,143 consecutive patients aged 80 years and older admitted between January 2004 and July 2009 to one of the ICUs of 21 Dutch hospitals. The prospective dataset was split into 30 equally sized consecutive subsets. Per subset, we measured the model's discrimination [area under the curve (AUC)], accuracy (Brier score), and standardized mortality ratio (SMR), both without and after repeated recalibration. All performance measures were considered to be stable if <2 consecutive points fell outside the green zone [mean +/- 2 standard deviation (SD)] and none fell outside the yellow zone (mean +/- 4SD) of pre control charts. We compared proportions of hospitals with SMR>1 without and after repeated recalibration for the year 2009. RESULTS: For all subsets, the AUCs were stable, but the Brier scores and SMRs were not. The SMR was downtrending, achieving levels significantly below 1. Repeated recalibration rendered it stable again. The proportions of hospitals with SMR>1 and SMR<1 changed from 15 versus 85% to 35 versus 65%. CONCLUSIONS: Variability over time may markedly vary among different performance measures, and infrequent model recalibration can result in improper assessment of the quality of care in many hospitals. We stress the importance of the timely recalibration and repeated validation of prognostic models over time. PMID- 22042521 TI - The relationship between neighborhood characteristics and recruitment into adolescent family-based substance use prevention programs. AB - Youth in disadvantaged neighborhoods are at risk for poor health outcomes. Characteristics of these neighborhoods may translate into intensified risk due to barriers utilizing preventive care such as substance use prevention programs. While family-level risks affect recruitment into prevention programs, few studies have addressed the influence of neighborhood risks. This study consists of 744 families with an 11- to 12-year-old child recruited for a family-based substance use prevention program. Using US Census data, logistic regressions showed neighborhoods were related to recruitment, beyond individual characteristics. Greater neighborhood unemployment was related to decreased agreement to participate in the study and lower rates of high school graduation were related to lower levels of actual enrolment. Conversely, higher rates of single-female headed households were related to increased agreement. Recruitment procedures may need to recognize the variety of barriers and enabling forces within the neighborhood in developing different strategies for the recruitment of youth and their families. PMID- 22042522 TI - Correlated regions of cerebral blood flow with clinical parameters in Parkinson's disease; comparison using 'Anatomy' and 'Talairach Daemon' software. AB - OBJECTIVES: We assign the anatomical names of functional activation regions in the brain, based on the probabilistic cyto-architectonic atlas by Anatomy 1.7 from an analysis of correlations between regional cerebral blood flow (rCBF) and clinical parameters of the non-demented Parkinson's disease (PD) patients by SPM8. We evaluated Anatomy 1.7 of SPM toolbox compared to 'Talairach Daemon' (TD) Client 2.4.2 software. METHODS: One hundred and thirty-six patients (mean age 60.0 +/- 9.09 years; 73 women and 63 men) with non-demented PD were selected. Tc 99m-HMPAO brain single-photon emission computed tomography (SPECT) scans were performed on the patients using a two-head gamma-camera. We analyzed the brain image of PD patients by SPM8 and found the anatomical names of correlated regions of rCBF perfusion with the clinical parameters using TD Client 2.4.2 and Anatomy 1.7. The SPM8 provided a correlation coefficient between clinical parameters and cerebral hypoperfusion by a simple regression method. To the clinical parameters were added age, duration of disease, education period, Hoehn and Yahr (H&Y) stage and Korean mini-mental state examination (K-MMSE) score. RESULTS: Age was correlated with cerebral perfusion in the Brodmann area (BA) 6 and BA 3b assigned by Anatomy 1.7 and BA 6 and pyramis in gray matter by TD Client 2.4.2 with p < 0.001 uncorrected. Also, assigned significant correlated regions were found in the left and right lobules VI (Hem) with duration of disease, in left and right lobules VIIa crus I (Hem) with education, in left insula (Ig2), left and right lobules VI (Hem) with H&Y, and in BA 4a and 6 with K-MMSE score with p < 0.05 uncorrected by Anatomy 1.7, respectively. Most areas of correlation were overlapped by two different anatomical labeling methods, but some correlation areas were found with different names. CONCLUSION: Age was the most significantly correlated clinical parameter with rCBF. TD Client found the exact anatomical name by the peak intensity position of the cluster while Anatomy 1.7 of SPM8 toolbox, using the cyto-architectonic probability maps, assigned the anatomical name by percentage value of the probability. PMID- 22042523 TI - Lemming winter habitat choice: a snow-fencing experiment. AB - The insulative value of early and deep winter snow is thought to enhance winter reproduction and survival by arctic lemmings (Lemmus and Dicrostonyx spp). This leads to the general hypothesis that landscapes with persistently low lemming population densities, or low amplitude population fluctuations, have a low proportion of the land base with deep snow. We experimentally tested a component of this hypothesis, that snow depth influences habitat choice, at three Canadian Arctic sites: Bylot Island, Nunavut; Herschel Island, Yukon; Komakuk Beach, Yukon. We used snow fencing to enhance snow depth on 9-ha tundra habitats, and measured the intensity of winter use of these and control areas by counting rodent winter nests in spring. At all three sites, the density of winter nests increased in treated areas compared to control areas after the treatment, and remained higher on treated areas during the treatment. The treatment was relaxed at one site, and winter nest density returned to pre-treatment levels. The rodents' proportional use of treated areas compared to adjacent control areas increased and remained higher during the treatment. At two of three sites, lemmings and voles showed significant attraction to the areas of deepest snow accumulation closest to the fences. The strength of the treatment effect appeared to depend on how quickly the ground level temperature regime became stable in autumn, coincident with snow depths near the hiemal threshold. Our results provide strong support for the hypothesis that snow depth is a primary determinant of winter habitat choice by tundra lemmings and voles. PMID- 22042524 TI - Population and behavioural responses of native prey to alien predation. AB - The introduction of invasive alien predators often has catastrophic effects on populations of naive native prey, but in situations where prey survive the initial impact a predator may act as a strong selective agent for prey that can discriminate and avoid it. Using two common species of Australian small mammals that have persisted in the presence of an alien predator, the European red fox Vulpes vulpes, for over a century, we hypothesised that populations of both would perform better where the activity of the predator was low than where it was high and that prey individuals would avoid signs of the predator's presence. We found no difference in prey abundance in sites with high and low fox activity, but survival of one species-the bush rat Rattus fuscipes-was almost twofold higher where fox activity was low. Juvenile, but not adult rats, avoided fox odour on traps, as did individuals of the second prey species, the brown antechinus, Antechinus stuartii. Both species also showed reduced activity at foraging trays bearing fox odour in giving-up density (GUD) experiments, although GUDs and avoidance of fox odour declined over time. Young rats avoided fox odour more strongly where fox activity was high than where it was low, but neither adult R. fuscipes nor A. stuartii responded differently to different levels of fox activity. Conservation managers often attempt to eliminate alien predators or to protect predator-naive prey in protected reserves. Our results suggest that, if predator pressure can be reduced, otherwise susceptible prey may survive the initial impact of an alien predator, and experience selection to discriminate cues to its presence and avoid it over the longer term. Although predator reduction is often feasible, identifying the level of reduction that will conserve prey and allow selection for avoidance remains an important challenge. PMID- 22042525 TI - Above- and belowground responses to nitrogen addition in a Chihuahuan Desert grassland. AB - Increased available soil nitrogen can increase biomass, lower species richness, alter soil chemistry and modify community structure in herbaceous ecosystems worldwide. Although increased nitrogen availability typically increases aboveground production and decreases species richness in mesic systems, the impacts of nitrogen additions on semiarid ecosystems remain unclear. To determine how a semiarid grassland responds to increased nitrogen availability, we examined plant community structure and above- and belowground net primary production in response to long-term nitrogen addition in a desert grassland in central New Mexico, USA. Plots were fertilized annually (10 g N m(-2)) since 1995 and NPP measured from 2004 to 2009. Differences in aboveground NPP between fertilized and control treatments occurred in 2004 following a prescribed fire and in 2006 when precipitation was double the long-term average during the summer monsoon. Presumably, nitrogen only became limiting once drought stress was alleviated. Belowground NPP was also related to precipitation, and greatest root growth occurred the year following the wettest summer, decreasing gradually thereafter. Belowground production was unrelated to aboveground production within years and unrelated to nitrogen enrichment. Species richness changed between years in response to seasonal precipitation variability, but was not altered by nitrogen addition. Community structure did respond to nitrogen fertilization primarily through increased abundance of two dominant perennial grasses. These results were contrary to most nitrogen addition studies that find increased biomass and decreased species richness with nitrogen fertilization. Therefore, factors other than nitrogen deposition, such as fire or drought, may play a stronger role in shaping semiarid grassland communities than soil fertility. PMID- 22042527 TI - The role of three-center/four-electron bonds in superelectrophilic dirhodium carbene and nitrene catalytic intermediates. AB - Three-center/four-electron (3c/4e) bonds are important bonding motifs that dictate the electronic structure, and thereby the reactivity, of metal-metal bonded carbene and nitrene intermediate complexes that are crucial to the dirhodium-catalyzed functionalization of hydrocarbons. In this Perspective article, general features of the 3c/4e bond are presented and discussed in comparison to two-center/two-electron (2c/2e) bonds. Specifically, 3c/4e bonding interactions lead to longer distances between the atoms involved and measurably weaker bonds. Additionally, excited states derived from the 3c/4e bonding manifold are lower in energy than those derived from a 2c/2e manifold, signifying a greater degree of reactivity in the former case. Three coterminous 3c/4e Ru-Ru N bonds are present in metal-metal/metal-ligand multiply bonded diruthenium terminal nitrido compounds. This bonding situation results in an unusual superelectrophilic character of the nitride nitrogen atom, exemplified by its insertion into aryl C-H bonds via an electrophilic aromatic substitution mechanism. The key catalytic intermediates in dirhodium-catalyzed C-H functionalization reactions, dirhodium carbene and dirhodium nitrene complexes, may also be described as superelectrophilic by virtue of 3c/4e Rh-Rh-C(or N) sigma and pi bonds. These 3c/4e bonding interactions set apart dirhodium carbene and nitrene intermediates from other, less electrophilic, carbene or nitrene species. PMID- 22042526 TI - A guided tour of large genome size in animals: what we know and where we are heading. AB - The study of genome size diversity is an ever-expanding field that is highly relevant in today's world of rapid and efficient DNA sequencing. Animal genome sizes range from 0.02 to 132.83 pg but the majority of animal genomes are small, with the most of these genome sizes being less than 5 pg. Animals with large genomes (> 10 pg) are scattered within some invertebrates, including the Platyhelminthes, crustaceans, and orthopterans, and also the vertebrates including the Actinopterygii, Chondrichthyes, and some amphibians. In this paper, we explore the connections between organismal phenotype, physiology, and ecology to genome size. We also discuss some of the molecular mechanisms of genome shrinkage and expansion obtained through comparative studies of species with full genome sequences and how this may apply to species with large genomes. As most animal species sequenced to date have been in the small range for genome size (especially invertebrates) due to sequencing costs and to difficulties associated with large genome assemblies, an understanding of the structural composition of large genomes is still lacking. Studies using next-generation sequencing are being attempted for the first time in animals with larger genomes. Such analyses using low genome coverage are providing a glimpse of the composition of repetitive elements in animals with more complex genomes. These future studies will allow a better understanding of factors leading to genomic obesity in animals. PMID- 22042528 TI - The effect of age and personality on the main cognitive processes in drivers. AB - OBJECTIVES: The purpose of this study is the evaluation of how the decline of cognitive abilities caused by aging is moderated by biologically determined personality dimensions: Neuroticism (N) and Extraversion (E). MATERIALS AND METHODS: The research was conducted with the participation of 160 men in good physical health, professional drivers, aged 20-70 (Mean = 40, SD = 11). Personality traits were measured using Eysenck's Personality Questionnaire - Revised (EPQ-R), while Ravens Progressive Matrices, Go/noGo Task and Peripheral Perception Test were used to evaluate cognitive processes. The score of Ravens Progressive Matrices was treated as a control variable. RESULTS: The results of the study, based on a Hierarchical Multiple Regression Analysis, indicate that besides the intelligence level, age is the best predictor of cognitive functioning level and that this influence is additionally moderated by the N trait level as well as, less frequently, by the interaction of age and E. CONCLUSION: This means that high N trait level increases the influence of age on cognitive functions decline. When the N trait level was low, the age differences in measures of cognitive performance were not significant. Thus, the level of N trait may play an important role in the process of cognitive aging. The results are discussed in the context of a driving safety research. PMID- 22042530 TI - Carpometacarpal subchondral cysts due to repetitive movements in shoemaker: a case report. AB - OBJECTIVES: Subchondral carpometacarpal cysts are classic and almost pathognomonic lesions found in workers using vibrating instruments over prolonged periods of time. MATERIALS AND METHODS: We present the case of a 53-year-old woman who worked for 30 years sewing shoe uppers, a task which required grasping firmly a pear-shaped handle awl and pushing it through the leather upper and the sole of the shoe, with combined flexion and supination movement of the wrist. After approximately 20 years of working, the patient noted gradual onset of paresthesias in the dominant (right) hand, with increasing difficulty in grasping the awl. Subsequent diagnosis of carpal tunnel syndrome was confirmed by electrophysiologic testing and its surgical release was performed. Nevertheless, hand pain, paresthesias and weakness persisted. RESULTS: Ultrasound of the snuffbox tendons excluded DeQuervain tenosynovitis. Radiographic imaging of the symptomatic hand showed carpometacarpal subchondral cystic formations. CONCLUSIONS: In addition to demonstrating the usefulness of radiographic imaging in patients with persistent hand pain post-carpal release, this case is important in illustrating that repetitive movements with high pressure over the palmar carpal area may cause bone cysts, even if the subjects do not use vibrating tools. PMID- 22042531 TI - Energy cost of spontaneous walking in Parkinson's disease patients. AB - In healthy subjects, comfortable walking minimizes the energy cost (E (c)) of locomotion. In Parkinson's disease (PD) patients walking is slower than in healthy subjects: this may increase E (c). Our aims were to analyze gait and E (c) in PD patients during walking, particularly at self-selected speed, and the possible pathological, mechanical, and cardiorespiratory limitations. Fourteen mild-to-moderate PD and 14 control subjects were enrolled. Subjects underwent 5 min walking tests at two speeds: self-selected and as-fast-as-possible speeds. Cardiopulmonary and gait parameters (heart rate, ventilation, gas exchanges, step count) were recorded. Velocity was reduced in PD compared to control subjects at both speeds (P < 0.05), and PD patients had shorter strides (P < 0.05) at both speeds and reduced cadence (P = 0.01) at fastest speed. No significant difference was found in E (c) at self-selected (0.12 +/- 0.04 versus 0.11 +/- 0.02 mLO(2) kg(-1) m(-1) in PD and control subjects, respectively) and maximal (0.14 +/- 0.03 versus 0.15 +/- 0.02 mLO(2) kg(-1) m(-1) in PD and control subjects, respectively) speed. However, the E (c) increment from self-selected to fastest velocity was significantly lower (P = 0.02) in PD patients. PD patients failed to walk at a self-selected speed, which minimizes the E (c). This could be mainly due to the inability to develop a wider stride. Cardiorespiratory adaptation was not affected, except for the possible reduced cardiac adaptation observed in some (28%) cases. Presumably, rehabilitation procedures that improve flexibility and step length may help maintain walking ability. PMID- 22042532 TI - Patient satisfaction with hospital care provided by hospitalists and primary care physicians. AB - BACKGROUND: Compared to hospital care provided by primary care physicians (PCPs), the hospitalist model provides equal-to-superior efficiency and outcomes; however, little is known about how the model affects patient satisfaction. METHODS: Random patient satisfaction telephone interviews were conducted on discharged adult medicine inpatients at 3 Massachusetts hospitals between 2003 and 2009. Questionnaires included variables assessing patient satisfaction with various physician care domains. Patient age, gender, admission year, education level, language, illness severity, emergency room admission status, institution, and attending physician type were extracted from billing records. We used adjusted multivariable models to compare patient satisfaction with hospitalists and PCPs for domains of: physician care quality, physician behavior, pain management, communication. RESULTS: Inpatients completed discharge surveys for 8295 encounters (3597 hospitalist, 4698 PCP). Multivariate-adjusted satisfaction scores for physician care quality were slightly higher for PCPs than hospitalists (4.24 vs 4.20, P = 0.04); there was no statistical difference at any individual hospital, and no difference among different hospitalist groups. Patient ratings of hospitalists and PCPs for behavior, pain control, and communication were equivalent (all P values >0.23). In multivariable models, hospitalists and PCPs had similar adjusted proportions in the highest satisfaction category (79.2% vs 80.5%, respectively, P = 0.17) and lowest category (5.1% vs 4.5%, respectively, P = 0.19). Quality ratings of both groups improved equivalently (P slope interaction = 0.47) but significantly over time (PCP 4.21 (2003) to 4.36 (2009), hospitalist 4.11 to 4.33, P Delta <0.001). CONCLUSIONS: Patients appear similarly satisfied with inpatient care provided by several hospitalist models and by primary care physicians. PMID- 22042533 TI - Impact of acute stress on human brain microstructure: An MR diffusion study of earthquake survivors. AB - A characterization of the impact of natural disasters on the brain of survivors is critical for a better understanding of posttraumatic responses and may inform the development of more effective early interventions. Here we report alterations in white matter microstructure in survivors soon after Wenchuan earthquake in China in 2008. Within 25 days after the Wenchuan earthquake, 44 healthy survivors were recruited and scanned on a 3T MR imaging system. The survivors were divided into two groups according to their self-rating anxiety scale (SAS) score, including the SAS(+) (SAS > 55 after correction) group and "SAS(-)" (SAS < 55 after correction) group. Thrity-two healthy volunteers were also recruited as control group before earthquake. Individual maps of fractional anisotropy (FA) were calculated and voxel-based analysis (VBA) was performed to allow the comparison between survivors and controls using ANCOVAs in SPM2. In addition, a correlation between SAS score and regional FA value was examined using Pearson's correlation analysis in SPSS 11.5. Compared with the healthy cohort, the whole group of 44 survivors showed significantly decreased FA values in the right prefrontal lobe, the parietal lobe, the basal ganglia, and the right parahippocampus. These effects did not appear to depend on self-rating anxiety. For the first time we provide evidence that acute trauma altered cerebral microstructure within the limbic system; furthermore, these alterations are evident shortly after the traumatic event, highlighting the need for early evaluation and intervention for trauma survivors. PMID- 22042534 TI - Traveling wave solutions in a plant population model with a seed bank. AB - We propose an integro-difference equation model to predict the spatial spread of a plant population with a seed bank. The formulation of the model consists of a nonmonotone convolution integral operator describing the recruitment and seed dispersal and a linear contraction operator addressing the effect of the seed bank. The recursion operator of the model is noncompact, which poses a challenge to establishing the existence of traveling wave solutions. We show that the model has a spreading speed, and prove that the spreading speed can be characterized as the slowest speed of a class of traveling wave solutions by using an asymptotic fixed point theorem. Our numerical simulations show that the seed bank has the stabilizing effect on the spatial patterns of traveling wave solutions. PMID- 22042535 TI - Mathematical properties of pump-leak models of cell volume control and electrolyte balance. AB - Homeostatic control of cell volume and intracellular electrolyte content is a fundamental problem in physiology and is central to the functioning of epithelial systems. These physiological processes are modeled using pump-leak models, a system of differential algebraic equations that describes the balance of ions and water flowing across the cell membrane. Despite their widespread use, very little is known about their mathematical properties. Here, we establish analytical results on the existence and stability of steady states for a general class of pump-leak models. We treat two cases. When the ion channel currents have a linear current-voltage relationship, we show that there is at most one steady state, and that the steady state is globally asymptotically stable. If there are no steady states, the cell volume tends to infinity with time. When minimal assumptions are placed on the properties of ion channel currents, we show that there is an asymptotically stable steady state so long as the pump current is not too large. The key analytical tool is a free energy relation satisfied by a general class of pump-leak models, which can be used as a Lyapunov function to study stability. PMID- 22042536 TI - Iowa Gambling Task in de novo Parkinson's disease: a comparison between good and poor performers. PMID- 22042537 TI - Inflammation regulates microRNA expression in cooperation with p53 and nitric oxide. AB - microRNA (miRNA) are small non-coding RNA targeting mRNAs leading to their instability and diminished translation. Altered expression of miRNA is associated with cancer. Inflammation and nitric oxide modulates the development of lymphomas in p53 knockout mice and there exists a negative feedback loop between p53 and NOS2. Using a genetic strategy, we tested the hypothesis that inflammation induced oxidative and nitrosative stress modulates miRNA expression in mouse model deficient in either p53 or NOS2. Mice treated with Corynebacterium parvum (C. parvum), to induce inflammation, clearly separated from controls by their miRNA profiles in wild-type, p53- and NOS2-knockout genetic backgrounds. C. parvum-induced inflammation significantly (p < 0.005) increased miR-21, miR-29b and miR-34a/b/c and decreased (p < 0.005) mir-29c and mir-181a/c expression in the spleen of C57BL mice. However, p53-knockout C57BL mice did not show a significant increase in the mir-34b/c or a decrease in mir-29c expression following C. parvum-induced inflammation. Expression of mir-21, mir-29b and mir 181a was independent of p53-status. NOS2-knockout C57BL mice showed a significant increase in miR-21 and miR-34a/b/c and decrease in miR-181a similar to the wild type (WT) mice following C. parvum-induced inflammation. However, in contrast to the WT mice, miR-29b/c expression was not affected following C. parvum-induced inflammation in NOS2 knockout mice. N-acetyl cysteine, an anti-oxidant, reduced the expression of miR-21 and miR-29b in C. parvum-treated WT mice (p < 0.005) as compared with control C. parvum-treated mice. These data are consistent with the hypothesis that inflammation modulates miRNA expression in vivo and the alteration in specific miRNA under an inflammatory microenvironment, can be influenced by p53 (miR-34b/c) and NO(*) (29b/c). PMID- 22042538 TI - Possibilities and limitations for high resolution small animal MRI on a clinical whole-body 3T scanner. AB - OBJECT: To investigate the potential of a clinical 3 T scanner to perform MRI of small rodents. MATERIALS AND METHODS: Different dedicated small animal coils and several imaging sequences were evaluated to optimize image quality with respect to SNR, contrast and spatial resolution. As an application, optimal grey-white matter contrast and resolution were investigated for rats. Furthermore, manganese enhanced MRI was applied in mice with unilateral crush injury of the optic nerve to investigate coil performance on topographic mapping of the visual projection. RESULTS: Differences in SNR and CNR up to factor 3 and more were observed between the investigated coils. The best grey-white matter contrast was achieved with a high resolution 3D T (2)-weighted TSE (SPACE) sequence. Delineation of the retino tectal projection and detection of defined visual pathway damage on the level of the optic nerve could be achieved by using a T (1)-weighted, 3D gradient echo sequence with isotropic resolution of (0.2 mm)(3). CONCLUSIONS: Experimental studies in small rodents requiring high spatial resolution can be performed by using a clinical 3 T scanner with appropriate dedicated coils. PMID- 22042539 TI - Prioritizing obesity in the city. AB - A decade ago, the World Health Organization declared obesity to be a global epidemic. Accordingly, there is a growing body of research examining how "obesogenic environments" contribute to the increasing prevalence of obesity. Using the ANGELO Framework, this research explores the role of municipal policies and practices in constructing obesogenic environments in two Southern Ontario cities in order to examine how socio-cultural and political environments shape excess body weight. Data was collected from municipal policy documents, public health websites, and key informants in Hamilton and Mississauga, Ontario, Canada. Results indicate that while the cities took different approaches to dealing with obesity, they both reflected the cities' overall prioritizing of health. Additionally, the findings reveal the pervasiveness of values and attitudes held in the socio-cultural environment in further shaping (and being shaped by) political as well as economic and physical environments in the cities. The importance of explicitly acknowledging the official discourse of the city, which this study demonstrates to be a significant factor in constructing obesogenic environments, is highlighted. Theoretical contributions and policy implications are also discussed. PMID- 22042540 TI - Are we looking for loads in all the right places? New research directions for studying the masticatory apparatus of New World monkeys. AB - New World monkeys display a wide range of masticatory apparatus morphologies related to their diverse diets and feeding strategies. While primatologists have completed many studies of the platyrrhine masticatory apparatus, particularly morphometric analyses, we collectively acknowledge key shortcomings in our understanding of the function and evolution of the platyrrhine feeding apparatus. Our goal in this contribution is to review several recent, and in most cases ongoing, efforts to address some of the deficits in our knowledge of how the platyrrhine skull is loaded during feeding. We specifically consider three broad research areas: (1) in vivo physiological studies documenting mandibular bone strains during feeding, (2) metric analyses assessing musculoskeletal functional morphology and performance, as well as (3) the initiation of a physiological ecology of feeding that measures in vivo masticatory mechanics in a natural environment. We draw several conclusions from these brief reviews. First, we need better documentation of in vivo strain patterns in the platyrrhine skull during feeding given their empirical role in developing adaptive hypotheses explaining masticatory apparatus form. Second, the greater accuracy of new technologies, such as CT scanning, will allow us to better describe the functional consequences of jaw form. Third, performance studies are generally lacking for platyrrhine jaws, muscles, and teeth and offer exciting avenues for linking form to feeding behavior and diet. Finally, attempts to bridge distinct research agendas, such as collecting in vivo physiological data during feeding in natural environments, present some of the greatest opportunities for novel insights into platyrrhine feeding biology. PMID- 22042541 TI - Presenting data: can you follow a recipe? PMID- 22042542 TI - Seamless networks of myocardial bioenergetics. PMID- 22042543 TI - Are we ready for a new mechanism of action underlying digitalis toxicity? PMID- 22042544 TI - Sex differences in the control of acral skin blood flow in humans: differential regulation of cyclooxygenase in alpha-adrenergic signalling. PMID- 22042545 TI - Serotonin, presynaptic 5-HT3 receptors and synaptic plasticity in the developing cerebellum. PMID- 22042546 TI - Purinergic regulation of K+ and Na+ transport by immortalized human mammary epithelial cell monolayers. PMID- 22042548 TI - Statistical perspectives: all together NOT. PMID- 22042550 TI - Development of a pediatric hospitalist sedation service: training and implementation. AB - OBJECTIVE: There is growing demand for safe and effective procedural sedation in pediatric facilities nationally. Currently, these needs are being met by a variety of providers and sedation techniques, including anesthesiologists, pediatric intensivists, emergency medicine physicians, and pediatric hospitalists. There is currently no consensus regarding the training required by non-anesthesiologists to provide safe sedation. We will outline the training method developed at St. Louis Children's Hospital. METHODS: In 2003, the Division of Pediatric Anesthesia at St. Louis Children's Hospital approached the Division of Pediatric Hospitalist Medicine as a resource to provide pediatric sedation outside of the operating room. Over the last seven years, Pediatric Hospitalist Sedation services have evolved into a three-tiered system of sedation providers. The first tier provides sedation services in the emergency unit (EU) and the Center for After Hours Referral for Emergency Services (CARES). The second tier provides sedation throughout the hospital including the EU, CARES, inpatient units, Ambulatory Procedure Center (APC), and Pediatric Acute Wound Service (PAWS); it also provides night/weekend sedation call for urgent needs. The third tier provides sedation in all of the second-tier locations, as well as utilizing propofol in the APC. RESULTS: This training program has resulted in a successful pediatric hospitalist sedation service. Based on fiscal year 2009 billing data, the division performed 2,471 sedations. We currently have 43 hospitalists providing Tier-One sedation, 18 Tier-Two providers, and six Tier-Three providers. CONCLUSIONS: A pediatric hospitalist sedation service with proper training and oversight can successfully augment sedation provided by anesthesiologists. PMID- 22042551 TI - A comparative study of recombinant mouse and human apurinic/apyrimidinic endonuclease. AB - Mammalian apurinic/apyrimidinic endonuclease (APE1) initiates the repair of abasic sites (AP-sites), which are highly toxic, mutagenic, and implicated in carcinogenesis. Also, reducing the activity of APE1 protein in cancer cells and tumors sensitizes mammalian tumor cells to a variety of laboratory and clinical chemotherapeutic agents. In general, mouse models are used in studies of basic mechanisms of carcinogenesis, as well as pre-clinical studies before transitioning into humans. Human APE1 (hAPE1) has previously been cloned, expressed, and extensively characterized. However, the knowledge regarding the characterization of mouse APE1 (mAPE1) is very limited. Here we have expressed and purified full-length hAPE1 and mAPE1 in and from E. coli to near homogeneity. mAPE1 showed comparable fast reaction kinetics to its human counterpart. Steady state enzyme kinetics showed an apparent K(m) of 91 nM and k(cat) of 4.2 s(-1) of mAPE1 for the THF cleavage reaction. For hAPE1 apparent K(m) and k(cat) were 82 nM and 3.2 s(-1), respectively, under similar reaction conditions. However, k(cat)/K(m) were in similar range for both APE1s. The optimum pH was in the range of 7.5-8 for both APE1s and had an optimal activity at 50-100 mM KCl, and they showed Mg(2+) dependence and abrogation of activity at high salt. Circular dichroism spectroscopy revealed that increasing the Mg(2+) concentration altered the ratio of "turns" to "beta-strands" for both proteins, and this change may be associated with the conformational changes required to achieve an active state. Overall, compared to hAPE1, mAPE1 has higher K(m) and k(cat) values. However, overall results from this study suggest that human and mouse APE1s have mostly similar biochemical and biophysical properties. Thus, the conclusions of mouse studies to elucidate APE1 biology and its role in carcinogenesis may be extrapolated to apply to human biology. This includes the development and validation of effective APE1 inhibitors as chemosensitizers in clinical studies. PMID- 22042552 TI - Thermodynamic and kinetic behaviour of [Pt(2-methylthiomethylpyridine)(OH2)2]2+. AB - The diaqua complex [Pt(2-methylthiomethylpyridine)(OH(2))(2)](2+), Pt(mtp), was synthesized and investigated thermodynamically as well as kinetically. Spectrophotometric acid-base titrations were performed to determine the pK(a) values of the two coordinated water ligands. A low pK(a1) value of 3.15 was observed for the water molecule trans to the pyridine donor, whereas a pK(a2) value of 6.84 was found for the water molecule trans to the labilising sulphur donor. The substitution of coordinated water by a series of sterically hindered S containing nucleophiles, viz. thiourea (tu), N,N'-dimethylthiourea (dmtu) and N,N,N',N'-tetramethylthiourea (tmtu), was studied under pseudo first-order conditions as a function of nucleophile concentration, pH (2, 4.75, 7.4), temperature and pressure, using stopped-flow techniques and UV-vis spectroscopy. In general the first substitution reaction takes place trans to the sulphur donor. At pH 2 the nucleophiles react in the order tu (634 +/- 10) > dmtu (507 +/ 5) ? tmtu (165 +/- 3 M(-1) s(-1) at 25 degrees C), which is caused by steric hindrance. The second observed reaction involves two steps, viz. the displacement of the second water ligand and dechelation of the pyridine ring with the third order rate constants 73.3 +/- 0.8 (tu), 22.1 +/- 0.1 (dmtu) and 6.8 +/- 0.2 M(-2) s(-1) (tmtu) at 25 degrees C. At pH 4.75 the reactions are in general slower due to the presence of aqua-hydroxo species. The same order in reactivity was found, viz. tu (106 +/- 1) > dmtu (72 +/- 1) ? tmtu (14.1 +/- 0.5 M(-1) s(-1) at 25 degrees C). No evidence for ring-dechelation could be observed under these conditions. At pH 7.4 the inert dihydroxo species is predominantly present in solution and consequently no substitution reaction was observed. Quantum chemical calculations were performed to support the interpretation and discussion of the experimental results. PMID- 22042553 TI - Differential microstructure and physiology of brain and bone metastases in a rat breast cancer model by diffusion and dynamic contrast enhanced MRI. AB - Pharmacological approaches to treat breast cancer metastases in the brain have been met with limited success. In part, the impermeability of the blood brain barrier (BBB) has hindered delivery of chemotherapeutic agents to metastatic tumors in the brain. BBB-permeable chemotherapeutic drugs are being developed, and noninvasively assessing the efficacy of these agents will be important in both preclinical and clinical settings. In this regard, dynamic contrast enhanced (DCE) and diffusion weighted imaging (DWI) are magnetic resonance imaging (MRI) techniques to monitor tumor vascular permeability and cellularity, respectively. In a rat model of metastatic breast cancer, we demonstrate that brain and bone metastases develop with distinct physiological characteristics as measured with MRI. Specifically, brain metastases have limited permeability of the BBB as assessed with DCE and an increased apparent diffusion coefficient (ADC) measured with DWI compared to the surrounding brain. Microscopically, brain metastases were highly infiltrative, grew through vessel co-option, and caused extensive edema and injury to the surrounding neurons and their dendrites. By comparison, metastases situated in the leptomenengies or in the bone had high vascular permeability and significantly lower ADC values suggestive of hypercellularity. On histological examination, tumors in the bone and leptomenengies were solid masses with distinct tumor margins. The different characteristics of these tissue sites highlight the influence of the microenvironment on metastatic tumor growth. In light of these results, the suitability of DWI and DCE to evaluate the response of chemotherapeutic and anti-angiogenic agents used to treat co-opted brain metastases, respectively, remains a formidable challenge. PMID- 22042554 TI - Down-regulation of matrix metalloproteinase-7 inhibits metastasis of human anaplastic thyroid cancer cell line. AB - Epigenetic drugs such as histone deacetylase inhibitors (HDACIs) possess anticancer properties due to its ability to regulate genes associated with tumor growth, differentiation, apoptosis and metastasis. In addition to its apoptotic effect, phenylbutyrate (PB), a carboxylic acid HDACI, inhibited an anaplastic (ATC) thyroid cancer cell line ARO from penetrating a matrigel coated transwell with concomitant suppression of a metastasis-associated gene, matrix metalloproteinase-7 (MMP-7) and stimulation of a transformation suppressor protein, reversion-inducing- cysteine-rich protein with Kazal motifs without affecting MMP-2 expression levels. Direct evidence suggesting MMP-7 down regulated cancer metastasis came from the observation of a decreased pulmonary metastasis in SCID mice xeno-transplanted with MMP-7-knocked-down ARO cells. In addition, H-89, a protein kinase A inhibitor, remarkably restored the down regulaed MMP-7 level treated by PB. Thus, the suppressive effect of PB on MMP-7 was partially carried out through H3 phosphoacetylation. To conclude, our findings suggest PB inhibits MMP-7 expression epigenetically through phosphoacetylation of histone proteins, and thereby, reduced invasive ability of an ATC thyroid cancer cell line. PMID- 22042555 TI - Cervical carcinoma-associated fibroblasts are DNA diploid and do not show evidence for somatic genetic alterations. AB - BACKGROUND: Cancer-associated fibroblasts (CAFs) have been recognized as important contributors to cancer development and progression. However, opposing evidence has been published whether CAFs, in addition to epigenetic, also undergo somatic genetic alterations and whether these changes contribute to carcinogenesis and tumour progression. METHODS: We combined multiparameter DNA flow cytometry, flow-sorting and 6K SNP-arrays to study DNA aneuploidy, % S phase, loss of heterozygosity (LOH) and copy number alterations (CNAs) in cervical cancer-associated stromal cell fractions (n = 57) from formalin-fixed, paraffin-embedded (FFPE) samples. Tissue sections were examined for the presence of CAFs. Microsatellite analysis was used to confirm LOH findings. RESULTS: Smooth muscle actin and vimentin immunohistochemistry verified the presence of CAFs in all cases tested. However, we found no evidence for DNA aneuploidy, somatic genetic alterations in the vimentin-positive stromal cell fractions of any samples, while high frequencies of DNA content abnormalities (43/57) and substantial numbers of CNAs and LOH were identified in the keratin-positive epithelial cell fractions. LOH hot-spots on chromosomes 3p, 4p and 6p found were confirmed by microsatellite analysis. CONCLUSION: From our study we conclude that stromal cell fractions from cervical carcinomas are DNA diploid, have a genotype undistinguishable from patient-matched normal tissue and are genetically stable. Using flow cytometry and SNP-arrays, stromal genetic changes do not seem to play a role during cervical carcinogenesis and progression. In addition, the stromal cell fraction of cervical carcinomas can be used as reference allowing large retrospective studies of archival FFPE tissues for which no normal reference tissue is available. PMID- 22042556 TI - The association between deployment-related posttraumatic growth among U.S. Army soldiers and negative behavioral health conditions. AB - OBJECTIVES: This study assessed posttraumatic growth (PTG) in a sample of U.S. Army Soldiers using the Post-Traumatic Growth Inventory (PTGI), and the relationship between PTG and negative behavioral health (BH) conditions. DESIGN: A sample of Soldiers with prior combat deployment experience (n = 1,834) completed an anonymous survey including demographics, the PTGI, and negative BH conditions. RESULTS: Among previously deployed Soldiers, those reporting the highest number of combat experiences also reported significantly higher overall PTG. A significant inverse relationship was observed between PTG and recent suicidal ideation, whereby Soldiers reporting recent suicidal ideation reported significantly lower overall PTG. CONCLUSIONS: This study quantified PTG resulting from deployment and demonstrated the degree to which combat experiences might result in PTG. PMID- 22042557 TI - Chloroform aerobic cometabolism by butane-growing Rhodococcus aetherovorans BCP1 in continuous-flow biofilm reactors. AB - This work focuses on chloroform (CF) cometabolism by a butane-grown aerobic pure culture (Rhodococcus aetherovorans BCP1) in continuous-flow biofilm reactors. The goals were to obtain preliminary information on the feasibility of CF biodegradation by BCP1 in biofilm reactors and to evaluate the applicability of the pulsed injection of growth substrate and oxygen to biofilm reactors. The attached-cell tests were initially conducted in a 0.165-L bioreactor and, then, scaled-up to a 1.772-L bioreactor. Glass cylinders were utilized as biofilm carriers. The continuous supply of growth substrate (butane), which led to the attainment of the highest CF degradation rate (8.4 mg(CF) day(-1) m (biofilm surface)(-2)), was compared with four schedules of butane and oxygen pulsed feeding. The pulsed injection technique allowed the attainment of a ratio of CF mass degraded per unit mass of butane supplied equal to 0.16 mg(CF) mg (butane)( 1), a value 4.4 times higher than that obtained with the continuous substrate supply. A procedure based on the utilization of integral mass balances and of average concentrations along the bioreactors resulted in a satisfactory match between the predicted and the experimental CF degradation performances, and can therefore be utilized to provide a guideline for optimizing the substrate pulsed injection schedule. PMID- 22042558 TI - Characterization of Th1- and Th2-type immune response in human multidrug resistant tuberculosis. AB - Multidrug-resistant tuberculosis (MDR-TB) has become a lethal global threat. Insights into the immune regulation of MDR-TB are urgently needed for the development of new treatments; however, the T cell response to an MDR-TB infection in human remains unclear. In the present study, the proportion of Th1 and Th2 cell subsets and the level of related T cell subset cytokines in peripheral blood were investigated. We detected that an MDR-TB infection resulted in suppressed Th1 and Th2 cell activation, which was more remarkable in patients with MDR-TB than that in drug-sensitive tuberculosis (DS-TB) sufferers when compared to healthy controls (HCs). In addition, MDR-TB infection down-regulated the expression of IFN-gamma, IL-2, and IL-10, and up-regulated IL-4, IL-6, and TNF-alpha expression. Our data suggest that the disturbance between protective and pathogenic effects induced by the immunosuppression of Th1- and Th2-type responses is a substantial characteristic of MDR-TB infections. PMID- 22042559 TI - The effect of diabetic control status on the clinical features of pulmonary tuberculosis. AB - The aim of this study was to determine whether control status of diabetes mellitus influences clinical and radiographic manifestations and treatment responses in patients with tuberculosis (TB). The medical records of 492 patients who started anti-TB medication between January 2005 and December 2009 were retrospectively reviewed. Diabetes was diagnosed in 124 patients (25.2%). Of these, 74 (59.7%) were uncontrolled (HbA1C>=7.0), 25 (20.2%) were controlled (HbA1C<7.0), and HbA1C levels were not assessed in the remaining 25 (20.2%). There were no differences in clinical symptoms between diabetics and non diabetics, regardless of diabetes control status. There were also no differences in radiographic findings or AFB results between controlled diabetics and non diabetics. However, uncontrolled diabetics had more cavitary lesions (p=0.008) and higher positive smear rates (p<0.001) compared with non-diabetics. After adjustment for age, cavities and positive smears before initiation of treatment, uncontrolled diabetes was a significant risk factor for a positive sputum culture at 2 months (odds ratio, 4.316; 95% CI, 1.306-14.267; p=0.017). Uncontrolled diabetics seem to have more cavities, higher positive smear rates and lack of culture conversion after two months of therapy. Therefore, TB patients with uncontrolled diabetes should be carefully managed and treated. PMID- 22042560 TI - Diversity of Mycobacterium avium subsp. hominissuis mycobacteria causing lymphadenitis, France. AB - The knowledge of Mycobacterium avium complex (MAC) genotypes responsible for lymphadenitis is limited. We retrospectively characterized all of the MAC isolates made in our laboratory in the last 18 years by sequence-based identification and genotyping, and compared the clinical and laboratory data for lymphadenitis-associated and non-lymphadenitis-associated MAC isolates. Of 67 MAC infected patients, 25 lymphadenitis patients were significantly younger than 42 non-lymphadenitis patients, while the male/female ratio did not significantly differ between the two groups. Cervical topography found in 76.5% of lymphadenitis patients was significantly more frequent in non-immunocompromised patients (p=0.04). M. avium subsp. hominissuis was identified in 53 patients (24 lymphadenitis, 29 non-lymphadenitis), M. colombiense in six patients (five non lymphadenitis, one lymphadenitis), M. intracellulare in four non-lymphadenitis patients, and M. chimaera in three non-lymphadenitis patients, while negative controls remained negative. M. hominissuis was significantly associated with lymphadenitis (p=0.03). M. hominissuis isolates yielded 15 genotypes in 29 non lymphadenitis isolates (molecular diversity, 0.622) versus 11 genotypes in 24 lymphadenitis isolates (molecular diversity, 0.578), demonstrating a non significant lower diversity of M. hominissuis isolates cultured from lymphadenitis. The genotypes did not correlate with the clinical features. These data suggest the presence of several environmental reservoirs for M. hominissuis causing lymphadenitis in France. PMID- 22042561 TI - Outcome of medium-dose VP-16/CY/TBI superior to CY/TBI as a conditioning regimen for allogeneic stem cell transplantation in adult patients with acute lymphoblastic leukemia. AB - The choice of conditioning regimen before allogeneic stem cell transplantation (SCT) in patients with acute lymphoblastic leukemia (ALL) is important. We retrospectively compared outcomes of medium-dose VP-16/cyclophosphamide/total body irradiation (VP/CY/TBI) regimen and CY/TBI. Five hundred and twenty-nine patients (VP/CY/TBI: n = 35, CY/TBI: n = 494) who met all of the following criteria were compared: first time for SCT, aged 15-59 years; first or second complete remission at SCT; bone marrow or peripheral blood as stem cell source; and HLA phenotypically matched donor. Median age of the patients was 34 years, and patients who received VP/CY/TBI were younger (28 vs. 34 years, P = 0.02). Cumulative incidences of relapse and non-relapse mortality (NRM) were higher for patients who received CY/TBI (P = 0.01 for relapse, P < 0.01 for NRM). After a median follow-up period of 36.9 months, 5-year overall survival (OS) rates were 82.2% in the VP/CY/TBI group and 55.2% in the CY/TBI group. OS, and disease-free survival (DFS) in the VP/CY/TBI group were shown to be significantly better by multivariate analysis [hazard ratio: 0.21 (95% confidence interval: 0.06-0.49) for DFS, hazard ratio: 0.25 (95% confidence interval: 0.08-0.59) for OS]. VP/CY/TBI was associated with a lower relapse rate and no increase in NRM, resulting in better survival than that in CY/TBI for adult ALL patients. PMID- 22042562 TI - GGF2 (Nrg1-beta3) treatment enhances NG2+ cell response and improves functional recovery after spinal cord injury. AB - The adult spinal cord contains a pool of endogenous glial precursor cells, which spontaneously respond to spinal cord injury (SCI) with increased proliferation. These include oligodendrocyte precursor cells that express the NG2 proteoglycan and can differentiate into mature oligodendrocytes. Thus, a potential approach for SCI treatment is to enhance the proliferation and differentiation of these cells to yield more functional mature glia and improve remyelination of surviving axons. We previously reported that soluble glial growth factor 2 (GGF2)- and basic fibroblast growth factor 2 (FGF2)-stimulated growth of NG2(+) cells purified from injured spinal cord in primary culture. This study examines the effects of systemic administration of GGF2 and/or FGF2 after standardized contusive SCI in vivo in both rat and mouse models. In Sprague-Dawley rats, 1 week of GGF2 administration, beginning 24 h after injury, enhanced NG2(+) cell proliferation, oligodendrogenesis, chronic white matter at the injury epicenter, and recovery of hind limb function. In 2',3'-cyclic-nucleotide 3' phosphodiesterase-enhanced green fluorescent protein mice, GGF2 treatment resulted in increased oligodendrogenesis and improved functional recovery, as well as elevated expression of the stem cell transcription factor Sox2 by oligodendrocyte lineage cells. Although oligodendrocyte number was increased chronically after SCI in GGF2-treated mice, no evidence of increased white matter was detected. However, GGF2 treatment significantly increased levels of P0 protein-containing peripheral myelin, produced by Schwann cells that infiltrate the injured spinal cord. Our results suggest that GGF2 may have therapeutic potential for SCI by enhancing endogenous recovery processes in a clinically relevant time frame. PMID- 22042563 TI - Multiple ileal perforations in a patient with Wegener's granulomatosis: a case report and literature review. AB - INTRODUCTION: Wegener's granulomatosis (WG) is a chronic, multisystemic disease of unknown etiology characterized by necrotizing vasculitis and granulomatous inflammation. WG primarily involves the upper and lower respiratory tract and kidneys, but it may also affect multiple other organs or tissues, including the gastrointestinal system. DISCUSSION: Gastrointestinal involvement is an extremely rare manifestation of this disease. Moreover, during the course of WG, intestinal perforation is extremely rare in patients with gastrointestinal involvement. To our knowledge, only 13 WG cases with intestinal perforation have been reported in the English language literature as of September 2011. CASE REPORT AND LITERATURE REVIEW: We herein present the case of a 47-year-old male patient with WG who was diagnosed with multiple ileal perforations and ileovesical fistulae. The exact pathogenesis of intestinal perforation in WG is not fully understood. However, early surgical intervention and appropriate management with immunosuppressive therapy can be important to lifesaving measures. A review of 13 cases reported in the English language literature is also discussed, together with the pathogenesis of this serious complication. PMID- 22042564 TI - Gastrointestinal metabolic surgery for the treatment of diabetic patients: a multi-institutional international study. AB - BACKGROUND: Gastrointestinal metabolic surgery has been proposed for the treatment of not well-controlled type 2 diabetes mellitus (T2DM) patients with a body mass index (BMI) <35 kg/m(2). This study aims to describe recent experience with surgical treatment of T2DM in Asian centers. METHODS: Patients aged 20 to 70 years with not well-controlled T2DM [glycated hemoglobin (HbA1C) >7.0%] and BMI < 35 kg/m(2) were included at five institutes between 2007 and 2010. The end point is T2DM remission, defined by fasting plasma glucose <110 mg/dl and HbA1C <6.0%. RESULTS: Of the 200 patients, 172 (86%) underwent gastric bypass, 24 (12%) underwent sleeve gastrectomy, and the other 4 underwent adjustable banding. Laparoscopic access was used in all the patients. Gender (66.5% female), age (mean 45.0 +/- 10.8), and HbA1C (mean 9.3 +/- 1.9%) did not differ between the procedure among the groups. Until now, 87 patients had 1-year data. One year after surgery, the mean BMI decreased from 28.5 +/- 3.0 to 23.4 +/- 2.3 kg/m(2) and HbA1C decreased to 6.3 +/- 0.5%. Remission of T2DM was achieved in 72.4% of the patients. Patients with a diabetes duration of <5 years had a better diabetes remission rate than patients with duration of diabetes >5 years (90.3% vs. 57.1%; p = 0.006). Patients with BMI > 30 kg/m(2) had a better diabetes remission rate than those with BMI < 30 kg/m(2) (78.7% vs. 62.5%; p = 0.027). Individuals who underwent gastric bypass loss more weight and had a higher diabetes remission rate than individuals who underwent restrictive-type procedures. Multivariate analysis confirmed that the duration of diabetes and the type of surgery predict the diabetes remission. No mortalities were reported and two (1.0%) patients had major morbidities. CONCLUSION: Gastrointestinal metabolic surgery is an effective treatment for not well-controlled T2DM treatment. Diabetes remission is significantly higher in those with duration of diabetes less than 5 years and BMI > 30 kg/m(2). PMID- 22042565 TI - Biliary dyskinesia: how effective is cholecystectomy? AB - INTRODUCTION: Studies on biliary dyskinesia have been based on short-term surgical follow-up and do not take into consideration that most patients are discharged from surgical follow-up after the first postoperative visit and that for persistent or recurrent symptoms they are frequently seen by primary care providers and subsequently referred to gastroenterologists. We aimed to study this pattern and assess which factors predict patients that will benefit from cholecystectomy. METHOD: This is a retrospective analysis of medical records of patients who underwent cholecystectomy for biliary dyskinesia from February 2001 to January 2010 with a minimum postoperative follow-up of 6 months. RESULTS: At initial surgical follow-up, 19 of 141 (13.4%) patients said they had persistent symptoms. However, when subsequent visits were analyzed, 61 of 141 (43.3%) patients with persistent or recurrent symptoms saw their primary care provider. These symptoms were epigastric or right upper quadrant pain in 43 patients or 30% of those undergoing cholecystectomy. The only factor that distinguished patients with and without resolution of symptoms after cholecystectomy was the pathologic finding of inflammation (p = 0.02). CONCLUSION: Cholecystectomy does not appear to be as effective for biliary dyskinesia when long-term follow-up is evaluated. PMID- 22042566 TI - Pain control and quality of life after pancreatectomy with islet autotransplantation for chronic pancreatitis. AB - INTRODUCTION: In selected patients with chronic pancreatitis, total pancreatectomy with islet autotransplantation can be effective for the treatment of intractable pain while ameliorating postoperative diabetes. Improved quality of life scores and decreased daily narcotic use, as indicators of successful pain relief, are expected after total pancreatectomy. These outcomes and their relationship have not been well examined in this patient group. METHODS: A prospectively collected database of patients undergoing extensive pancreatectomy with islet autotransplantation for pancreatitis was reviewed. Data pertaining to daily oral morphine equivalents (MEs) and quality of life (QOL), as measured by the SF-12 questionnaire, in the preoperative and postoperative period were reviewed. Approval from the IRB for the evaluation of human subjects was obtained. RESULTS: Over a 20-month period, 33 patients (25 women, median age 42) underwent extensive pancreatectomy with islet autotransplantation for pancreatitis. Mean follow-up was 9 months with a range of 6-12 months. Postoperative complications occurred in 16 patients (48%). Preoperative QOL scores were a mean 25 for physical component and 32 for mental health component. Postoperatively, physical component scores averaged 33 at 6 months (p = 0.025) and 36 at 12 months (mean increase of 11); the mental health component scores averaged 43 at 6 months (p = 0.007) and 44 at 12 months (mean increase of 12). Preoperative MEs averaged 357 mg daily. At discharge from the hospital, this number increased to 536 mg average MEs daily, a 50% increase, as expected after major surgery in the chronic pain patient. At 6 months, 15 out of 31 patients (48%) required less daily MEs than preoperatively and averaged 161 mg daily ( 55%). By 12 months, 11 out of 17 patients (65%) required less daily MEs than preoperatively and averaged 128 mg daily (-64%); four were narcotic-free (23%). Of the six patients who did not decrease their analgesic requirements at 1 year, five (83%) still had an improved physical QOL score (one patient was unchanged) and all six had an improved mental health QOL. CONCLUSION: Total pancreatectomy with islet autotransplant is an effective surgery for end-stage chronic pancreatitis. Quality of life improves early postoperatively while decreased narcotic analgesia requirements occur later. Both improved quality of life and decreased narcotic analgesia requirements continue to occur at least up to 1 year postoperatively. Further investigation is needed to assess the durability of total pancreatectomy with islet autotransplantation for severe chronic pancreatitis with respect to pain relief and improved quality of life. PMID- 22042567 TI - Regulation of retinoblastoma protein (Rb) by p21 is critical for adaptation to massive small bowel resection. AB - BACKGROUND: Adaptation following massive intestinal loss is characterized by increased villus height and crypt depth. Previously, we demonstrated that p21 null mice do not adapt after small bowel resection (SBR). As retinoblastoma protein (Rb) levels are elevated in p21-null crypt cells, we first sought to determine whether Rb is required for normal adaptation. Next, we tested whether Rb expression is responsible for blocked adaptation in p21-nulls. METHODS: Genetically manipulated mice and wild-type (WT) littermates underwent either 50% SBR or sham operation. The intestine was harvested at 3, 7, or 28 days later and intestinal adaptation was evaluated. Enterocytes were isolated and protein levels evaluated by Western blot and quantified by optical density. RESULTS: Rb-null mice demonstrated increased villus height, crypt depth, and proliferative rate at baseline, but there was no further increase following SBR. Deletion of one Rb allele lowered Rb expression and restored resection-induced adaptation responses in p21-null mice. CONCLUSION: Rb is specifically required for resection-induced adaptation. Restoration of adaptation in p21-null mice by lowering Rb expression suggests a crucial mechanistic role for Rb in the regulation of intestinal adaptation by p21. PMID- 22042568 TI - Laparoscopic assisted ERCP in Roux-en-Y gastric bypass (RYGB) surgery patients. AB - BACKGROUND: Performing endoscopic retrograde cholangiopancreatography (ERCP) in patients with prior Roux-en-Y gastric bypass (RYGB) surgery is challenging. Despite advancements in endoscopic technology, reaching the duodenum and entering the bile duct is still difficult. Laparoscopic assisted ERCP (LAERCP) allows the duodenum to be accessed through the excluded stomach. OBJECTIVES: The objective of this study is to evaluate the success rates and complications in patients with prior RYGB anatomy who underwent LAERCP in a tertiary care center. PATIENTS: Consecutive patients undergoing LAERCP between 2005 and 2010 were used for this study. OUTCOMES: Biliary/pancreatic cannulation, endoscopic/laparoscopic interventions, postprocedure complications, postprocedure hospital stay, and procedure time were observed in this study. RESULTS: Fifteen patients with post RYGB surgery underwent LAERCP. Endoscopic antegrade access to the papilla was achieved through the gastric remnant in all. Cannulation and interventions in the pancreaticobiliary tree were successful in all cases. Therapeutic interventions included biliary sphincterotomy in 14 and pancreatic sphincterotomy in two patients. There were no postoperative complications related to the endoscopic portion of the procedure. The mean duration of the procedure and the median postprocedure hospital stay were 45 min and 2 days, respectively. CONCLUSION: Laparoscopic assisted ERC is a useful approach in the diagnosis and treatment of pancreaticobiliary conditions in patients with RYGB. PMID- 22042569 TI - Chronic noninfectious uveitis associated with Vogt-Koyanagi-Harada disease treated with low-dose weekly systemic methotrexate. PMID- 22042570 TI - OPA1 mutations in Japanese patients suspected to have autosomal dominant optic atrophy. AB - PURPOSE: To report three types of heterozygous mutations in the OPA1 gene in five patients from three families with autosomal dominant optic atrophy (ADOA, MIM#165500). METHODS: DNA was extracted from the leukocytes of the peripheral blood. For mtDNA, mutations were examined at positions 11778, 3460 and 14484. For the OPA1 gene, the exons were amplified by PCR and mutations were detected by restriction enzymes or the dye terminator method. RESULTS: We detected three types of OPA1 mutation but no mtDNA mutations. In the OPA1 gene, heterozygous frameshift mutations from codon 903 due to a four-base pair deletion in exon 27 were detected in three patients from one family (c.2708_2711delTTAG, p.V903GfsX905). A heterozygous mutation due to a three-base pair deletion in exon 17, leading to a one-amino acid deletion (c.1618_1620delACT, p.T540del), and a heterozygous mutation due to a one-base substitution in exon 11, leading to a stop codon (c.1084G>T, p.E362X), were detected in sporadic cases. CONCLUSION: OPA1 mutations existed in three Japanese families with ADOA. After a detailed clinical assessment of the proband, the screening of the OPA1 gene may be helpful for precise diagnosis of ADOA, provided the relevant information of the family members is limited. PMID- 22042571 TI - Molecular analysis of Korean patients with oculocutaneous albinism. AB - PURPOSE: To perform molecular analysis of five Korean patients with oculocutaneous albinism (OCA) and review the clinical and genetic characteristics of 21 Korean OCA patients. METHODS: TYR, OCA2 and SLC45A2 were analyzed by direct DNA sequencing in five unrelated OCA patients who received thorough ophthalmic evaluation. RESULTS: We identified three different TYR mutations in three patients (c.929dupC, R278X, and R52I), among which the latter two had been previously reported in other populations, but are reported here for the first time in a Korean context. In one patient we identified two different mutations of OCA2 [c.1784+1G>A and c.1842G>T (K614N)]. One patient was confirmed to have OCA4 by detecting two SLC45A2 mutations [c.469G>A (D157N) and c.686G>A (C229Y)]. OCA1A (66.7%) was the most common subtype in 21 Korean albinism patients, and 70% of patients were heterozygotes for 2 different mutational alleles. c.929dupC (54.8%) and R77Q (16.1%) were the most frequent mutational alleles of TYR in Koreans. CONCLUSIONS: Three mutational alleles, R278X and R52I of the TYR gene and C229Y of the SLC45A2 gene, are added to the mutational spectra of Korean patients with OCA, and we report the first Korean case of OCA2 with the OCA2 gene mutations. PMID- 22042572 TI - Diversity of long terminal repeat retrotransposon genome distribution in natural populations of the wild diploid wheat Aegilops speltoides. AB - The environment can have a decisive influence on the structure of the genome, changing it in a certain direction. Therefore, the genomic distribution of environmentally sensitive transposable elements may vary measurably across a species area. In the present research, we aimed to detect and evaluate the level of LTR retrotransposon intraspecific variability in Aegilops speltoides (2n = 2x = 14), a wild cross-pollinated relative of cultivated wheat. The interretrotransposon amplified polymorphism (IRAP) protocol was applied to detect and evaluate the level of retrotransposon intraspecific variability in Ae. speltoides and closely related species. IRAP analysis revealed significant diversity in TE distribution. Various genotypes from the 13 explored populations significantly differ with respect to the patterns of the four explored LTR retrotransposons (WIS2, Wilma, Daniela, and Fatima). This diversity points to a constant ongoing process of LTR retrotransposon fraction restructuring in populations of Ae. speltoides throughout the species' range and within single populations in time. Maximum changes were recorded in genotypes from small stressed populations. Principal component analysis showed that the dynamics of the Fatima element significantly differ from those of WIS2, Wilma, and Daniela. In terms of relationships between Sitopsis species, IRAP analysis revealed a grouping with Ae. sharonensis and Ae. longissima forming a separate unit, Ae. speltoides appearing as a dispersed group, and Ae. bicornis being in an intermediate position. IRAP display data revealed dynamic changes in LTR retrotransposon fractions in the genome of Ae. speltoides. The process is permanent and population specific, ultimately leading to the separation of small stressed populations from the main group. PMID- 22042573 TI - Altitudinal variation at duplicated beta-globin genes in deer mice: effects of selection, recombination, and gene conversion. AB - Spatially varying selection on a given polymorphism is expected to produce a localized peak in the between-population component of nucleotide diversity, and theory suggests that the chromosomal extent of elevated differentiation may be enhanced in cases where tandemly linked genes contribute to fitness variation. An intriguing example is provided by the tandemly duplicated beta-globin genes of deer mice (Peromyscus maniculatus), which contribute to adaptive differentiation in blood-oxygen affinity between high- and low-altitude populations. Remarkably, the two beta-globin genes segregate the same pair of functionally distinct alleles due to a history of interparalog gene conversion and alleles of the same functional type are in perfect coupling-phase linkage disequilibrium (LD). Here we report a multilocus analysis of nucleotide polymorphism and LD in highland and lowland mice with different genetic backgrounds at the beta-globin genes. The analysis of haplotype structure revealed a paradoxical pattern whereby perfect LD between the two beta-globin paralogs (which are separated by 16.2 kb) is maintained in spite of the fact that LD within both paralogs decays to background levels over physical distances of less than 1 kb. The survey of nucleotide polymorphism revealed that elevated levels of altitudinal differentiation at each of the beta-globin genes drop away quite rapidly in the external flanking regions (upstream of the 5' paralog and downstream of the 3' paralog), but the level of differentiation remains unexpectedly high across the intergenic region. Observed patterns of diversity and haplotype structure are difficult to reconcile with expectations of a two-locus selection model with multiplicative fitness. PMID- 22042574 TI - Sperm development and motility are regulated by PP1 phosphatases in Caenorhabditis elegans. AB - Sperm from different species have evolved distinctive motility structures, including tubulin-based flagella in mammals and major sperm protein (MSP)-based pseudopods in nematodes. Despite such divergence, we show that sperm-specific PP1 phosphatases, which are required for male fertility in mouse, function in multiple processes in the development and motility of Caenorhabditis elegans amoeboid sperm. We used live-imaging analysis to show the PP1 phosphatases GSP-3 and GSP-4 (GSP-3/4) are required to partition chromosomes during sperm meiosis. Postmeiosis, tracking fluorescently labeled sperm revealed that both male and hermaphrodite sperm lacking GSP-3/4 are immotile. Genetic and in vitro activation assays show lack of GSP-3/4 causes defects in pseudopod development and the rate of pseudopodial treadmilling. Further, GSP-3/4 are required for the localization dynamics of MSP. GSP-3/4 shift localization in concert with MSP from fibrous bodies that sequester MSP at the base of the pseudopod, where directed MSP disassembly facilitates pseudopod contraction. Consistent with a role for GSP-3/4 as a spatial regulator of MSP disassembly, MSP is mislocalized in sperm lacking GSP-3/4. Although a requirement for PP1 phosphatases in nematode and mammalian sperm suggests evolutionary conservation, we show PP1s have independently evolved sperm-specific paralogs in separate lineages. Thus PP1 phosphatases are highly adaptable and employed across a broad range of sexually reproducing species to regulate male fertility. PMID- 22042575 TI - Estimation of quantitative trait locus effects with epistasis by variational Bayes algorithms. AB - Bayesian hierarchical shrinkage methods have been widely used for quantitative trait locus mapping. From the computational perspective, the application of the Markov chain Monte Carlo (MCMC) method is not optimal for high-dimensional problems such as the ones arising in epistatic analysis. Maximum a posteriori (MAP) estimation can be a faster alternative, but it usually produces only point estimates without providing any measures of uncertainty (i.e., interval estimates). The variational Bayes method, stemming from the mean field theory in theoretical physics, is regarded as a compromise between MAP and MCMC estimation, which can be efficiently computed and produces the uncertainty measures of the estimates. Furthermore, variational Bayes methods can be regarded as the extension of traditional expectation-maximization (EM) algorithms and can be applied to a broader class of Bayesian models. Thus, the use of variational Bayes algorithms based on three hierarchical shrinkage models including Bayesian adaptive shrinkage, Bayesian LASSO, and extended Bayesian LASSO is proposed here. These methods performed generally well and were found to be highly competitive with their MCMC counterparts in our example analyses. The use of posterior credible intervals and permutation tests are considered for decision making between quantitative trait loci (QTL) and non-QTL. The performance of the presented models is also compared with R/qtlbim and R/BhGLM packages, using a previously studied simulated public epistatic data set. PMID- 22042576 TI - Complex population dynamics and the coalescent under neutrality. AB - Estimates of the coalescent effective population size N(e) can be poorly correlated with the true population size. The relationship between N(e) and the population size is sensitive to the way in which birth and death rates vary over time. The problem of inference is exacerbated when the mechanisms underlying population dynamics are complex and depend on many parameters. In instances where nonparametric estimators of N(e) such as the skyline struggle to reproduce the correct demographic history, model-based estimators that can draw on prior information about population size and growth rates may be more efficient. A coalescent model is developed for a large class of populations such that the demographic history is described by a deterministic nonlinear dynamical system of arbitrary dimension. This class of demographic model differs from those typically used in population genetics. Birth and death rates are not fixed, and no assumptions are made regarding the fraction of the population sampled. Furthermore, the population may be structured in such a way that gene copies reproduce both within and across demes. For this large class of models, it is shown how to derive the rate of coalescence, as well as the likelihood of a gene genealogy with heterochronous sampling and labeled taxa, and how to simulate a coalescent tree conditional on a complex demographic history. This theoretical framework encapsulates many of the models used by ecologists and epidemiologists and should facilitate the integration of population genetics with the study of mathematical population dynamics. PMID- 22042577 TI - Transcriptional regulation and the diversification of metabolism in wine yeast strains. AB - Transcription factors and their binding sites have been proposed as primary targets of evolutionary adaptation because changes to single transcription factors can lead to far-reaching changes in gene expression patterns. Nevertheless, there is very little concrete evidence for such evolutionary changes. Industrial wine yeast strains, of the species Saccharomyces cerevisiae, are a geno- and phenotypically diverse group of organisms that have adapted to the ecological niches of industrial winemaking environments and have been selected to produce specific styles of wine. Variation in transcriptional regulation among wine yeast strains may be responsible for many of the observed differences and specific adaptations to different fermentative conditions in the context of commercial winemaking. We analyzed gene expression profiles of wine yeast strains to assess the impact of transcription factor expression on metabolic networks. The data provide new insights into the molecular basis of variations in gene expression in industrial strains and their consequent effects on metabolic networks important to wine fermentation. We show that the metabolic phenotype of a strain can be shifted in a relatively predictable manner by changing expression levels of individual transcription factors, opening opportunities to modify transcription networks to achieve desirable outcomes. PMID- 22042578 TI - Measuring selection coefficients below 10(-3): method, questions, and prospects. AB - Measuring fitness with precision is a key issue in evolutionary biology, particularly in studying mutations of small effects. It is usually thought that sampling error and drift prevent precise measurement of very small fitness effects. We circumvented these limits by using a new combined approach to measuring and analyzing fitness. We estimated the mutational fitness effect (MFE) of three independent mini-Tn10 transposon insertion mutations by conducting competition experiments in large populations of Escherichia coli under controlled laboratory conditions. Using flow cytometry to assess genotype frequencies from very large samples alleviated the problem of sampling error, while the effect of drift was controlled by using large populations and massive replication of fitness measures. Furthermore, with a set of four competition experiments between ancestral and mutant genotypes, we were able to decompose fitness measures into four estimated parameters that account for fitness effects of our fluorescent marker (alpha), the mutation (beta), epistasis between the mutation and the marker (gamma), and departure from transitivity (tau). Our method allowed us to estimate mean selection coefficients to a precision of 2 * 10(-4). We also found small, but significant, epistatic interactions between the allelic effects of mutations and markers and confirmed that fitness effects were transitive in most cases. Unexpectedly, we also detected variation in measures of s that were significantly bigger than expected due to drift alone, indicating the existence of cryptic variation, even in fully controlled experiments. Overall our results indicate that selection coefficients are best understood as being distributed, representing a limit on the precision with which selection can be measured, even under controlled laboratory conditions. PMID- 22042579 TI - Contarini's syndrome: bilateral pleural effusion, each side from different causes. AB - Bilateral pleural effusions usually have a single causative factor, such as heart failure or malignancy. Contarini's syndrome refers to the occurrence of bilateral pleural fluid accumulation which can be explained by a different cause for each side. Literature search finds, along with 5 new descriptions from our center, totaled 12 cases. A frequent combination is that of a parapneumonic effusion that triggers heart failure, which in turn produces a contralateral transudate. PMID- 22042580 TI - Obsessive-compulsive disorder with predominantly scrupulous symptoms: clinical and religious characteristics. AB - OBJECTIVES: Scrupulosity is a relatively common but understudied subtype of obsessive-compulsive disorder (OCD) characterized by religious or moral fears. It is difficult to treat and frequently disabling. We examined scrupulosity as it relates to (a) treatment-seeking behavior and perceived treatment gains, (b) the perceived effect of symptoms on religious experience, and (c) conceptions of God. METHOD: Seventy-two individuals with scrupulous OCD (mean age = 36; 70% women) and 75 individuals with nonscrupulous OCD (mean age = 38; 81% women) completed an internet-based survey. RESULTS: The groups did not differ on demographic variables or overall OCD severity. Compared with the nonscrupulous group, the scrupulous group was (a) more religious, (b) more likely to seek pastoral counseling, (c) less likely to seek medication treatment, and (d) more likely to report that symptoms interfered with their religious experience. Indeed, most scrupulous individuals endorsed that their symptoms interfered with their religious experience. Scrupulous individuals with a more negative concept of God experienced more severe symptoms, whereas a positive description of God was unrelated to severity of scrupulosity in this group. Nearly one in five scrupulous participants reported no religious affiliation. CONCLUSIONS: Scrupulous individuals have unique treatment-seeking preferences. Moreover, most scrupulous individuals perceive their symptoms as interfering with their religious experience. Focusing on the religious costs and benefits of scrupulous rituals might have clinical utility. Finally, scrupulous individuals with a more negative concept of God experienced more severe symptoms. Future research is necessary to evaluate whether addressing such concepts can improve treatment outcome. PMID- 22042581 TI - A (New World monkey) tree grows in Brooklyn. PMID- 22042582 TI - Mentorship for participants in a laparoscopic colectomy course. AB - BACKGROUND: Despite data suggesting improved outcomes with laparoscopic colectomy (LC), less than 10% of colectomies in the Unites States are currently performed laparoscopically. One mechanism for incorporating LC into practice is to attend an LC course (LCC). Postcourse mentorship is recommended by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and the American Society of Colon and Rectal Surgeons (ASCRS), in addition to course participation, to encourage adoption of the new techniques. Recommendations also include access to at least 25 colectomies annually. Because the use of LC likely will increase, access to mentorship is an important consideration for LCC participants. This study aimed to evaluate mentorship access and related factors for participants in an ongoing LCC. METHODS: Participants in seven consecutive single-center LCCs were anonymously surveyed regarding age, specialty, surgical experience, practice, and mentorship availability. Factors associated with mentorship were identified via chi-square and univariate logistic regression. RESULTS: Of the 90 participants surveyed, 81 (90%) were men, 51 (56.7%) were general surgeons, 43 (48.9%) were older than 40 years, and 49 (54.4%) had access to a mentor. A majority of the participants (86.7%) performed five or fewer open colorectal cases per month, and 81 (90%) performed five or fewer noncolorectal advanced laparoscopic cases monthly. Factors associated with lack of mentor access included age older than 40 years (P = 0.004), practice as a general surgeon (P = 0.014), and status as a senior attending surgeon (P = 0.029). CONCLUSIONS: A significant number of surgeons (45.6%) participating in LCC have limited or no access to mentors. In particular, older surgeons, senior attending surgeons, and general surgeons have the least access to mentors. To encourage adoption of LC, training methods should be adopted that accommodate general surgeons, surgeons with a limited advanced laparoscopic case load, and surgeons without access to mentors. Possible strategies include longer or multisession courses, simulator training, and remote mentoring. PMID- 22042583 TI - Miniature surgical robot for laparoendoscopic single-incision colectomy. AB - BACKGROUND: This study aimed to demonstrate the effectiveness of using a multifunctional miniature in vivo robotic platform to perform a single-incision colectomy. Standard laparoscopic techniques require multiple ports. A miniature robotic platform to be inserted completely into the peritoneal cavity through a single incision has been designed and built. The robot can be quickly repositioned, thus enabling multiquadrant access to the abdominal cavity. METHODS: The miniature in vivo robotic platform used in this study consists of a multifunctional robot and a remote surgeon interface. The robot is composed of two arms with shoulder and elbow joints. Each forearm is equipped with specialized interchangeable end effectors (i.e., graspers and monopolar electrocautery). RESULTS: Five robotic colectomies were performed in a porcine model. For each procedure, the robot was completely inserted into the peritoneal cavity, and the surgeon manipulated the user interface to control the robot to perform the colectomy. The robot mobilized the colon from its lateral retroperitoneal attachments and assisted in the placement of a standard stapler to transect the sigmoid colon. This objective was completed for all five colectomies without any complications. CONCLUSIONS: The adoption of both laparoscopic and single-incision colectomies currently is constrained by the inadequacies of existing instruments. The described multifunctional robot provides a platform that overcomes existing limitations by operating completely within one incision in the peritoneal cavity and by improving visualization and dexterity. By repositioning the small robot to the area of the colon to be mobilized, the ability of the surgeon to perform complex surgical tasks is improved. Furthermore, the success of the robot in performing a completely in vivo colectomy suggests the feasibility of using this robotic platform to perform other complex surgeries through a single incision. PMID- 22042584 TI - Observational clinical human reliability analysis (OCHRA) for competency assessment in laparoscopic colorectal surgery at the specialist level. AB - BACKGROUND: There are no valid and reliable tools to assess competency in advanced laparoscopic surgery at a specialist level. The observational clinical human reliability analysis (OCHRA) may have the required characteristics of such a tool. The aim of this study was to evaluate construct and concurrent validity of OCHRA for competency assessment at a specialist level. METHODS: Thirty-two video-recorded laparoscopic colorectal resections, performed by experts and delegates of the National Training Program in England, were evaluated. Each video was analysed using OCHRA by identifying errors enacted during surgery. The number of tissue-handling, instrument-misuse, and consequential errors was recorded using video-rating software. Times spent on dissecting (D) and on exposing (E) tissues were also measured (D/E ratio). In addition, two independent expert surgeons globally assessed each video regarding competency (pass vs. fail). Logistic regression was used to predict outcomes. RESULTS: A total of 399 errors were identified. There was a significant difference when comparing the expert, pass, and fail groups for total errors (median counts for experts = 4, pass = 10, fail = 17; P < 0.001). When comparing the pass and fail groups excluding experts, differences could be found for tissue-handling errors (7 vs. 12; P = 0.005), but not for consequential errors (4 vs. 7; P = 0.059) and instrument-handling errors (4 vs. 5; P = 0.320). The D/E ratio was significantly lower for delegates than for experts (0.6 vs. 1.0; P = 0.001). When all four independent variables were used to predict delegates who passed or failed, the area under the receiver operating characteristic curve was 0.867, sensitivity was 71.4%, and specificity was 90.9%. CONCLUSION: OCHRA is a valid tool for assessing competency at a specialist level in advanced laparoscopic surgery. It has the potential to be used for recertification and revalidation of specialists. PMID- 22042585 TI - Therapeutic approach of human peritoneal carcinomatosis with Dbait in combination with capnoperitoneum: proof of concept. AB - BACKGROUND: Peritoneal carcinomatosis is an unmet medical need. Laparoscopy offers a unique opportunity to control and to steer the operating environment during surgery by loading carbon dioxide with a therapeutic substance and creating the so-called therapeutic capnoperitoneum. We have treated a human sample of peritoneal carcinomatosis from an endometrial adenocarcinoma ex vivo just after surgery. METHODS: A nontoxic therapeutic agent (Dbait) was aerosolized into a box containing diseased human peritoneum under a pressure of 12 mmHg CO(2). Dbait (noncoding DNA fragments) acts through jamming DNA damage sensing and signaling, ultimately inhibiting DNA repair system of cancer cells. Dbait were coupled to cholesterol molecules to facilitate intracellular uptake, and to Cyanine (Cy5) to allow detection by fluorescence. In a control experiment, the same solution was applied to the other half of the sample using conventional lavage. RESULTS: Physical results revealed fluorescence within the tumor up to 1 mm depth in the therapeutic capnoperitoneum sample and no uptake in the lavage sample. Biological results showed intranuclear phosphorylation of H2AX in the nebulized sample and no activity in the lavage sample. Importantly, tumor nodules showed more activity than the neighbor, normal peritoneum. Detection of histone gamma-H2AX (phosphorylated H2AX) reveals activation of DNA-dependent protein kinase (DNA-PK) by Dbait, which has been shown to be the key step for sensitization to genotoxic therapy. CONCLUSIONS: Dbait are taken up by cancer cells and have a biological activity up to 1 mm depth. Nebulization of the molecule is significantly more effective than conventional lavage. This proof of principle supports the need for clinical studies applying therapeutic capnoperitoneum together with Dbait for treating peritoneal carcinomatosis. PMID- 22042586 TI - Laparoscopic Nissen fundoplication with or without short gastric vessel division: a meta-analysis. AB - OBJECTIVE: The aim of this work is to systematically analyse the prospective randomised controlled trials on laparoscopic Nissen fundoplication (LNF) with and without short gastric vessel division (SGVD) for management of gastro-oesophageal reflux disease (GORD). METHODS: After an extensive literature search, all previous trials on laparoscopic Nissen fundoplication with and without SGVD for management of GORD were assessed. Those meeting study quality criteria were analysed to generate summative data expressed by standardised mean difference (SMD) and risk ratio (RR). RESULTS: Five randomised controlled trials on 388 patients qualified for the meta-analysis. There were 194 patients in the no-SGVD group and 194 patients in the SGVD group. No-SGVD was associated with shorter operative time and length of stay. In both fixed- and random-effects models, there were no statistically significant differences in laparoscopic to open conversion rate or complications between the two groups. Three trials presented data on 1-year follow-up, with 118 patients in the no-SGVD group and 112 patients in the SGVD group. There was no statistically significant difference in heartburn, dysphagia, regurgitation or gas bloat syndrome between these two groups. Two trials presented data on 10-year follow-up, with 84 patients in the no-SGVD group and 86 patients in the SGVD group. There was no significant difference in heartburn, dysphagia, regurgitation or gas bloat syndrome between these two groups either. There was no heterogeneity between trials. CONCLUSIONS: Based on this review, SGVD in LNF is associated with longer operative time and hospital stay. However, there is no difference in terms of functional outcomes for 1- and 10-year follow-up. Routine use of SGVD may therefore not be necessary in LNF. PMID- 22042587 TI - Comprehensive evaluation of endoscopic fundoplication using the EsophyXTM device. AB - BACKGROUND: There are limited studies that evaluate the efficacy of endoscopic fundoplication (EF) for gastroesophageal reflux disease (GERD) with the EsophyXTM device, especially with the most recent procedural iteration (TIF-2). This study was a prospective evaluation of our early experience with this device and procedure. METHODS: Data were collected prospectively on 23 consecutive patients undergoing EF (March 2009 to August 2010). All patients completed a symptom questionnaire assessing frequency and severity of gastrointestinal and respiratory symptoms, 24-h pH, and manometry studies preoperatively and were encouraged to repeat these at 6 months. RESULTS: All patients had abnormal pH studies and were on proton-pump inhibitor (PPI) therapy prior to EF. Median age was 47 years (19-62 years), and six (23%) were male. Nine (41%) patients had Body Mass Index (BMI) >= 30 kg/m(2), and three (14%) had a small hiatal hernia (<= 2 cm). The procedure was aborted in two patients for retained food. Three patients underwent subsequent laparoscopic Nissen fundoplication for persistent or recurrent symptoms. Median hospitalization was 1 day, and there were no major perioperative complications. At 6 month follow-up, 19 (86%) patients completed a symptom questionnaire, and 14 (64%) and 11 (50%) patients underwent pH and manometry studies, respectively. There was a significant reduction in heartburn (P = 0.02), total percentage acid contact time (P = 0.002), DeMeester score (P = 0.002), and PPI use (P = 0.003). Overall, 8 out of 14 (57%) patients had abnormal pH studies and 11 out of 19 (58%) remained on PPI therapy at 6 months. CONCLUSION: EF with EsophyXTM is associated with significant reduction in heartburn and abnormal acid exposure at 6 months, although the majority of patients did not experience normalization of their pH studies and remained on PPI therapy. The procedure has an acceptable safety profile, but the question remains as to whether it is effective enough to warrant a place in the armamentarium for the treatment of GERD. PMID- 22042588 TI - Benefit of "transparent soft-short-hood on the scope" for colonoscopy among experienced gastroenterologists and gastroenterologist trainee: a randomized, controlled trial. AB - BACKGROUND: The attachment of a transparent hood to the colonoscope tip has been reported to offer some benefits, such as enabling the endoscopist to perform the colonoscopy more easily and to save time. However, there have been no randomized, controlled trials concerning these benefits, nor have any reports been published regarding the use of hoods for the purpose of training colonoscopists. Therefore, we conducted this study to evaluate the possible benefits of the transparent soft short hood when used by both experienced and trainee endoscopist groups. METHODS: This randomized, controlled trial to assess the results of using a transparent soft short hood attached to the tip of the colonoscope was undertaken by two groups of investigators: experienced endoscopists and gastroenterologist trainees. The cecal and ileal intubation times, as well as the doses of sedative medication required, were analyzed. RESULTS: A total of 112 patients, 65 of whom were female, underwent colonoscopy by 2 endoscopists and 5 gastroenterologist trainees. Colonoscopy was complete in 100% of the patients. The study showed significant shortening of the cecal intubation time when using the soft short hood, in both the endoscopist and gastroenterologist trainee groups (6.8/4.61 min, P = 0.006; and 9.36/7.36 min, P = 0.03). The ileal intubation time had a trend to be significantly less when using the transparent hood in the trainee group (126.4/52.9 s), although this was not statistically significant (P = 0.08). The average dose of propofol, when using the transparent hood, was significantly lower in the endoscopist group (180/120 mg, P = 0.001). No significant complications occurred in the hood or non-hood groups. CONCLUSIONS: The transparent soft short hood shortened the cecal intubation time in both the experienced endoscopist and gastroenterologist trainee groups, as well as reducing the dose of sedative medication required in the experienced endoscopist group. Interestingly, it also reduced the trainee ileal intubation time. The attachment of this type of hood enabled both the experienced endoscopists and gastroenterological trainees to perform colonoscopy more quickly and easily, without any complications. PMID- 22042589 TI - Endoscopic full-thickness plication versus laparoscopic fundoplication: a prospective study on quality of life and symptom control. AB - BACKGROUND: Endoscopic antireflux techniques have emerged as alternative therapies for gastroesophageal reflux disease (GERD). Endoscopic plication receives continuing interest as an effective and safe procedure. This treatment option has not been the subject of comparison with well-established operative therapies to date. The present study aimed at comparatively evaluating the effectiveness of endoscopic plication and laparoscopic fundoplication in terms of quality of life and symptom control. METHODS: Between October 2006 and April 2010, 60 patients with documented GERD were randomly assigned to undergo either endoscopic plication or laparoscopic fundoplication. Quality-of-life scores and symptom grading were recorded before treatment and at 3- and 12-month follow-up. Outcomes were compared with the statistical significance set at a p value of 0.05. RESULTS: Twenty-nine patients from the endoscopic group and 27 patients from the operative group were available at follow-up. Quality-of-life scores showed a substantial and similar increase for both groups after treatment. Symptoms of heartburn (p < 0.02), regurgitation (p < 0.004), and asthma (p = 0.03) were significantly improved in the endoscopic group, whereas laparoscopic fundoplication was more effective in controlling symptoms of heartburn (p < 0.01) and regurgitation (p < 0.05) compared to the endoscopic procedure. CONCLUSIONS: Endoscopic plication and laparoscopic fundoplication resulted in significant symptom improvement with similar quality-of-life scores in a selected patient population with GERD, whereas operative treatment was more effective in the relief of heartburn and regurgitation at the expense of higher short-term dysphagia rates. PMID- 22042590 TI - Laser application enables awake thoracoscopic resection of pulmonary nodules with minimal access. AB - BACKGROUND: Thoracoscopic resection of indeterminate pulmonary nodules is most commonly performed through three trocars using an endoscopic stapler. We assessed the safety, feasibility, and results of laser resection via minimal access under only local anesthesia. METHODS: Between September 2009 and June 2010, excision of subpleural nodules using laser application under only local anesthesia was performed in 28 patients (Laser group). A 2-mm trocar (minigrasper) and an 11-mm trocar (operating scope) were used. Anesthesia time, surgery time, global operating room time, chest tube time, piritramid dose, and hospital stay were assessed and compared with data from a patient group (n = 28) that required nodule resection through three trocars using an endoscopic stapler under general anesthesia (Control group). RESULTS: There was no mortality or major morbidity. There was no difference in technical feasibility between the groups. Two patients in the Laser group and one patient in the Control group required conversion to thoracotomy due to severe adhesions. The mean nodule size was 0.9 +/- 0.2 cm in the Laser group and 1.0 +/- 0.3 cm in the Control group (P = 0.05). Comparisons of Laser group results with Control group results showed that in the Laser group, anesthesia time (3 +/- 0.7 vs. 42 +/- 6.3 min, P < 0.001), global operating room time (51 +/- 4.8 vs. 88 +/- 10.8 min, P < 0.001), piritramid dose (65.9 +/- 30.5 vs. 109.1 +/- 21.9 mg, P < 0.001), and hospital stay (2.3 +/- 0.9 vs. 3.2 +/- 0.6 days, P < 0.001) were significantly reduced. Patients' satisfaction was high. Ninety-eight percent of patients said they would undergo this surgery again. CONCLUSION: Awake thoracoscopic laser resection of subpleural pulmonary nodules proved safe and feasible. This technique may enable further reduction of invasiveness, length of hospital stay, and costs in selected patients. PMID- 22042591 TI - Management of non-midline incisional hernia by the laparoscopic approach: results of a long-term follow-up prospective study. AB - BACKGROUND: The role of the laparoscopic approach in the repair of non-midline incisional hernias is controversial due to the absence of adequate scientific studies. This study aimed to determine the safety and efficacy of laparoscopic repair for non-midline incisional hernias. METHODS: This prospective clinical study was conducted in an abdominal wall unit of a teaching hospital. Patients underwent surgery for non-midline incisional hernias using the laparoscopic approach (n = 73) and were classified into three groups: subcostal, iliac, and lumbar. The primary end point was recurrence. The secondary end points were intraoperative parameters, comorbidity, and patient outcomes. The median follow up period was 62 months (range, 36-170 months). RESULTS: No hospital stay was needed for 34% of the patients. The remaining patients needed an average hospital stay of 2.7 days. The most frequent morbidity was hematoma. The overall recurrence rate was 8.2% and was higher for the subcostal hernias (25%). The three groups differed in size, local morbidity, and recurrence (P < 0.05). The independent risk factors for recurrence were size (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.08-4.33) and local morbidity (HR 30.62; 95% CI 1.22 768-82). The best predictor of recurrence was a hernia diameter greater than 15 cm. The only predictive factor of local morbidity was obesity (P < 0.007). CONCLUSIONS: The laparoscopic approach is a safe and effective treatment for non midline incisional hernias. Caution should be taken with subcostal hernias, obese patients, and a defect size greater than 15 cm. An algorithm is suggested to guide the "rational" treatment of non-midline incisional hernias. PMID- 22042592 TI - Criterion-based laparoscopic training reduces total training time. AB - INTRODUCTION: The benefits of criterion-based laparoscopic training over time oriented training are unclear. The purpose of this study is to compare these types of training based on training outcome and time efficiency. METHODS: During four training sessions within 1 week (one session per day) 34 medical interns (no laparoscopic experience) practiced on two basic tasks on the Simbionix LAP Mentor virtual-reality (VR) simulator: 'clipping and grasping' and 'cutting'. Group C (criterion-based) (N = 17) trained to reach predefined criteria and stopped training in each session when these criteria were met, with a maximum training time of 1 h. Group T (time-based) (N = 17) trained for a fixed time of 1 h each session. Retention of skills was assessed 1 week after training. In addition, transferability of skills was established using the Haptica ProMIS augmented reality simulator. RESULTS: Both groups improved their performance significantly over the course of the training sessions (Wilcoxon signed ranks, P < 0.05). Both groups showed skill transferability and skill retention. When comparing the performance parameters of group C and group T, their performances in the first, the last and the retention training sessions did not differ significantly (Mann Whitney U test, P > 0.05). The average number of repetitions needed to meet the criteria also did not differ between the groups. Overall, group C spent less time training on the simulator than did group T (74:48 and 120:10 min, respectively; P < 0.001). Group C performed significantly fewer repetitions of each task, overall and in session 2, 3 and 4. CONCLUSIONS: Criterion-based training of basic laparoscopic skills can reduce the overall training time with no impact on training outcome, transferability or retention of skills. Criterion-based should be the training of choice in laparoscopic skills curricula. PMID- 22042593 TI - Minimally invasive esophagectomy: thoracoscopic esophageal mobilization for esophageal cancer with the patient in prone position. AB - BACKGROUND: Surgical resection is the mainstay treatment for resectable esophageal cancer. Minimally invasive esophagectomy is performed with increasing frequency and proves to be a safe and effective surgical alternative to the open technique. Minimally invasive esophagectomy using thoracoscopic esophageal mobilization with the patient in prone position seems to offer some advantages with regard to surgeon ergonomics and clinical outcome. METHODS: Between July 2005 and September 2010, 46 patients (35 men and 11 women) underwent minimally invasive esophagectomy in the prone position at the authors' institution. Three patients had previously undergone a thoracic intervention (one patient had previously undergone left pneumonectomy because of lung cancer). The preoperative indication was squamous cell carcinoma for 35 patients and adenocarcinoma for 11 patients. In one case, the histology of the biopsy samples showed a squamous cell carcinoma with neuroendocrine differentiation. Neoadjuvant treatment was administered to 15 patients. RESULTS: All 46 patients underwent esophagectomy using minimally invasive thoracic mobilization of the esophagus with the patient in prone position. The abdominal stage of intervention was performed by laparoscopy for 37 patients and by laparotomy for 9 patients. No thoracotomic conversion was performed. In all cases, a cervical end-to-side anastomosis was performed using a circular stapler. The mean operative time was 263 min. The median intensive care unit stay was 2 days, and the median postoperative hospital stay was 15 days. The mean number of procured lymph nodes was 13. The perioperative morbidity rate was 37%, and the perioperative mortality rate was 4.4%. CONCLUSIONS: Minimally invasive esophagectomy is safe and technically feasible. It entails a lower mortality rate and a shorter hospital stay than those reported in most open series. Thoracoscopy with the patient in prone position offers results comparable with those obtained using other minimally invasive techniques regarding the number of procured lymph nodes. This technique shows considerable advantages such as improved surgeon ergonomics, increased operative field exposure, and satisfactory respiratory results. PMID- 22042594 TI - Complex caring trajectories in community mental health: contingencies, divisions of labor and care coordination. AB - The concept of 'trajectory' refers to the unfolding of individual service users' health and illness experiences, the organization of health and social care work surrounding them and the impact this work has on people involved. Using qualitative data from a study completed in two sites in Wales we first reveal the complex character of trajectories encountered in the community mental health field. We show how these can be shaped by features peculiar to mental ill-health per se, and by features with organizational origins. We then use our data to lay bare true divisions of labor. Mental health professionals featured prominently in our study. We also reveal relatively invisible contributions made by professionals on the periphery, support workers, unpaid lay carers and service users. In examining the significance of our findings we identify particular lessons for mental health practitioners, managers and policymakers sharing concerns for the coordination of care. PMID- 22042595 TI - Is 26 + 26 smaller than 24 + 28? Estimating the approximate magnitude of repeated versus different numbers. AB - It has recently been suggested that regardless of the dimension at hand (i.e., numerosity, length, time), similar operational mechanisms are involved in the comparison process based on approximate magnitude representation. One piece of evidence for this hypothesis lies in the presence of similar behavioral effects for any comparison (i.e., the distance effect). In the case of length comparison, the comparison process can be biased by summation toward either an underestimation or an overestimation: The sum of equal-size stimuli is underestimated, whereas the sum of different-size stimuli is overestimated. Relying on the hypothesis that similar operational mechanisms underlie the comparison process of any magnitude, we aim at extending these findings to another magnitude dimension. A number comparison task with digit numbers was used in the two experiments reported presently. The objective was to investigate whether summation also biases magnitude representation of numerical and symbolic information. The results provided evidence that the summation bias can also apply to numerical magnitude comparison, since the sum of repeated numbers (26 + 26) was underestimated whereas the sum of different numbers (24 + 28) was overestimated. We propose that these effects could be accounted for by a heuristic linking cognitive effort and magnitude estimation. PMID- 22042596 TI - Parafoveal processing in reading. AB - The present review summarizes research investigating how words are identified parafoveally (and foveally) in reading. Parafoveal and foveal processing are compared when no other concurrent task is required (e.g., in single-word recognition tasks) and when both are required simultaneously (e.g., during reading). We first review methodologies used to study parafoveal processing (e.g., corpus analyses and experimental manipulations, including gaze-contingent display change experiments such as the boundary, moving window, moving mask, and fast priming paradigms). We then turn to a discussion of the levels of representation at which words are processed (e.g., orthographic, phonological, morphological, lexical, syntactic, and semantic). Next, we review relevant research regarding parafoveal processing, summarizing the extent to which words are processed at each of those levels of representation. We then review some of the most controversial aspects of parafoveal processing, as they relate to reading: (1) word skipping, (2) parafoveal-on-foveal effects, and (3) n + 1 and n + 2 preview benefit effects. Finally, we summarize two of the most advanced models of eye movements during reading and how they address foveal and parafoveal processing. PMID- 22042597 TI - Sense of self-determination and the suicidal experience. A phenomenological approach. AB - In this paper phenomenological descriptions of the experiential structures of suicidality and of self-determined behaviour are given; an understanding of the possible scopes and forms of lived self-determination in suicidal mental life is offered. Two possible limits of lived self-determination are described: suicide is always experienced as minimally self-determined, because it is the last active and effective behaviour, even in blackest despair; suicide can never be experienced as fully self-determined, even if valued as the authentic thing to do, because no retrospective re-evaluation from some future vantage is possible. The phenomenological descriptions of the possible scope of lived self determination in suicidality, presented in this paper, should prove to be extremely helpful in three different fields of interest: (a) ethical debates regarding the pros and cons of autonomous or heteronomous suicide; (b) clinical day-to-day practice with respect to treating suicidal people; (c) people who suffered a suicidal crisis, attempted suicide or lost loved ones through suicides. (155 words). PMID- 22042598 TI - The principle of proportionality revisited: interpretations and applications. AB - The principle of proportionality is used in many different contexts. Some of these uses and contexts are first briefly indicated. This paper focusses on the use of this principle as a moral principle. I argue that under certain conditions the principle of proportionality is helpful as a guide in decision-making. But it needs to be clarified and to be used with some flexibility as a context-dependent principle. Several interpretations of the principle are distinguished, using three conditions as a starting point: importance of objective, relevance of means, and most favourable option. The principle is then tested against an example, which suggests that a fourth condition, focusing on non-excessiveness, needs to be added. I will distinguish between three main interpretations of the principle, some primarily with uses in research ethics, others with uses in other areas of bioethics, for instance in comparisons of therapeutic means and ends. The relations between the principle of proportionality and the precautionary principle are explored in the following section. It is concluded that the principles are different and may even clash. In the next section the principle of proportionality is applied to some medical examples drawn from research ethics and bioethics. In concluding, the status of the principle of proportionality as a moral principle is discussed. What has been achieved so far and what remains to be done is finally summarized. PMID- 22042599 TI - Immobilized thermolysin for highly efficient production of low-molecular-weight protamine--an attractive cell-penetrating peptide for macromolecular drug delivery applications. AB - Macromolecules present a remarkable potential as future therapeutics. However, their translation into clinical practice has been hampered by an inherently low bioavailability. Cell-penetrating peptides (CPP) have been recently shown to significantly improve on the bioavailability of macromolecules. Yet, the high cost associated with development and production of these peptides is a major factor hindering their rapid deployment beyond the laboratory. Here, we describe a facile and robust methodology for efficient and large-scale production of low molecular-weight protamine-a potent CPP of great clinical potential. Our methodology is based on the immobilization of thermolysin, an enzyme catalyzing digestion of native protamine, on chemically surface-modified gels produced by silica sol-gel chemistry. Thermolysin was immobilized at extremely high matrix loading of 733 mg/g matrix and exhibited good thermal and pH stability, indicating robustness with respect to processing conditions. The mechanical properties of the silica matrix further allowed utilization of the immobilized thermolysin in both batch and packed-bed reactor systems to produce the LMWP peptide in high yields. Results presented here are of high significance as this efficient and cost-effective production of high purity LMWP could enable clinical translation of many potential macromolecular drugs. PMID- 22042600 TI - Lysosomal exocytosis in Schwann cells contributes to axon remyelination. AB - Myelin biogenesis is a complex process involving coordinated exocytosis, endocytosis, mRNA transport, and cytoskeletal dynamics. Although abnormalities of myelin are common in lysosomal storage diseases, our understanding of the role of lysosomes in the formation and maintenance of myelin is still limited. Here, we show that late endosomes/lysosomes in Schwann cells contain abundant myelin protein P0, which accounts for over half the total protein of compact myelin in the peripheral nervous system and exhibit Ca(2+) -dependent exocytosis in response to various stimuli. Downregulation of Rab27a, a small GTPase required for the trafficking of the secretory lysosomes to the plasma membrane, largely blocked lysosomal exocytosis in Schwann cells and reduced the remyelination of regenerated sciatic nerve. These findings highlight a novel role for lysosomes in Schwann cells and suggest that the regulated lysosome exocytosis in Schwann cells may have important physiological and pathological significance in the peripheral nervous system. PMID- 22042601 TI - Punctuated equilibria and Indonesian art. PMID- 22042602 TI - Average group behavior does not represent individual behavior in classical conditioning of the honeybee. AB - Conditioned behavior as observed during classical conditioning in a group of identically treated animals provides insights into the physiological process of learning and memory formation. However, several studies in vertebrates found a remarkable difference between the group-average behavioral performance and the behavioral characteristics of individual animals. Here, we analyzed a large number of data (1640 animals) on olfactory conditioning in the honeybee (Apis mellifera). The data acquired during absolute and differential classical conditioning differed with respect to the number of conditioning trials, the conditioned odors, the intertrial intervals, and the time of retention tests. We further investigated data in which animals were tested for spontaneous recovery from extinction. In all data sets we found that the gradually increasing group average learning curve did not adequately represent the behavior of individual animals. Individual behavior was characterized by a rapid and stable acquisition of the conditioned response (CR), as well as by a rapid and stable cessation of the CR following unrewarded stimuli. In addition, we present and evaluate different model hypotheses on how honeybees form associations during classical conditioning by implementing a gradual learning process on the one hand and an all-or-none learning process on the other hand. In summary, our findings advise that individual behavior should be recognized as a meaningful predictor for the internal state of a honeybee--irrespective of the group-average behavioral performance. PMID- 22042603 TI - Morphological correlates of the grooming claw in distal phalanges of platyrrhines and other primates: a preliminary study. AB - Grooming claws are present on the second pedal digits of strepsirhines and on the second and third pedal digits of tarsiers. However, their presence in New World monkeys is often overlooked. As such, the absence of a grooming claw is generally considered an anthropoid synapomorphy. This study utilizes a quantitative multivariate analysis to define grooming claw morphology and document its presence in platyrrhine monkeys. Our results show that owl monkeys possess grooming claws similar to those of strepsirhines, while titi monkeys possess grooming claw-like morphology. Therefore, we conclude that anthropoids are not clearly united by the absence of a grooming claw. Furthermore, due to their presence in three major primate clades, we infer that it is likely that a grooming claw was present on the second pedal digit of the ancestor of living primates. Therefore, we advise the reassessment of fossil adapids in light of the anatomical correlates described here. This should increase resolution on the homology and polarity of grooming claw morphology, and, therefore, will help provide a sharper picture of primate evolution. PMID- 22042605 TI - Health care reform and the primary care workforce bottleneck. AB - To establish and sustain the high-performing health care system envisioned in the Affordable Care Act (ACA), current provisions in the law to strengthen the primary care workforce must be funded, implemented, and tested. However, the United States is heading towards a severe primary care workforce bottleneck due to ballooning demand and vanishing supply. Demand will be fueled by the "silver tsunami" of 80 million Americans retiring over the next 20 years and the expanded insurance coverage for 32 million Americans in the ACA. The primary care workforce is declining because of decreased production and accelerated attrition. To mitigate the looming primary care bottleneck, even bolder policies will be needed to attract, train, and sustain a sufficient number of primary care professionals. General internists must continue their vital leadership in this effort. PMID- 22042606 TI - Evaluation of sun protection factor of cosmetic formulations by a simple visual in vitro method mimicking the in vivo method. AB - A new concept for in vitro visual evaluation of sun protection factor (SPF) of cosmetic formulations based on a supramolecular ultraviolet (UV) dosimeter was clearly demonstrated. The method closely parallels the method validated for in vivo evaluation and relies on the determination of the slightest perceptible bleaching of an iron-complex dye/nanocrystalline-titanium dioxide interface (UV dosimeter) in combination with an artificial skin substrate simulating the actual human skin in the presence and absence of a cosmetic formulation. The successful evaluation of SPF was ensured by the similarity of the erythema response of our dosimeter and human skin to UV light irradiation. A good linear correlation of in vitro and in vivo data up to SPF 40 confirmed the effectiveness of such a simple, cheap, and fast method. In short, here we unravel a convenient and accessible visual FPS evaluation method that can help improving the control on cosmetic products contributing to the reduction of skin cancer, one of the critical public health issues nowadays. PMID- 22042607 TI - Unveiling the mysteries in the trees: the anatomical record explores the anatomy and evolution of New World monkeys. PMID- 22042608 TI - Olive oil mill wastewaters before and after treatment: a critical review from the ecotoxicological point of view. AB - The olive oil mill wastewater (OMW) is a problematic and polluting effluent which may degrade the soil and water quality, with critical negative impacts on ecosystems functions and services provided. The main purpose of this review paper is presenting the state of the art of OMW treatments focusing on their efficiency to reduce OMW toxicity, and emphasizing the role of ecotoxicological tests on the evaluation of such efficiency before the up-scale of treatment methodologies being considered. In the majority of research works, the reduction of OMW toxicity is related to the degradation of phenolic compounds (considered as the main responsible for the toxic effects of OMW on seed germination, on bacteria, and on different species of soil and aquatic invertebrates) or the decrease of chemical oxygen demand content, which is not scientifically sound. Batteries of ecotoxicological tests are not applied before and after OMW treatments as they should be, thus leading to knowledge gaps in terms of accurate and real assessment of OMW toxicity. Although the toxicity of OMW is usually high, the evaluation of effects on sub-lethal endpoints, on individual and multispecies test systems, are currently lacking, and the real impacts yielded by its dilution, in freshwater trophic chains of receiving systems can not be assessed. As far as the terrestrial compartment is considered, ecotoxicological data available include tests only with plants and the evaluation of soil microbial parameters, reflecting concerns with the impacts on crops when using OMW for irrigation purposes. The evaluation of its ecotoxicity to other edaphic species were not performed giving rise to a completely lack of knowledge about the consequences of such practice on other soil functions. OMW production is a great environmental problem in Mediterranean countries; hence, engineers, chemists and ecotoxicologists should face this problem together to find an ecologically friend solution. PMID- 22042609 TI - Identification of novel potential HIF-prolyl hydroxylase inhibitors by in silico screening. AB - Suppression of HIF-prolyl hydroxylase (PHD) activity by small-molecule inhibitors leads to the stabilization of hypoxia inducible factor and has been recognized as promising drug target for the treatment of ischemic diseases. In this study, pharmacophore-based virtual screening and molecular docking approaches were concurrently used with suitable modifications to identify target-specific PHD inhibitors with better absorption, distribution, metabolism, and excretion properties and to readily minimize false positives and false negatives. A customized method based on the active site information of the enzyme was used to generate a pharmacophore hypothesis (AAANR). The hypothesis was validated and utilized for chemical database screening and the retrieved hit compounds were subjected to molecular docking for further refinement. AAANR hypothesis comprised three H-bond acceptor, one negative ionizable group and one aromatic ring feature. The hypothesis was validated using decoy set with a goodness of fit score of 2 and was used as a 3D query for database screening. After manual selection, molecular docking and further refinement based on the molecular interactions of inhibitors with the essential amino acid residues, 18 hits with good absorption, distribution, metabolism, and excretion (ADME) properties were selected as excellent PHD inhibitors. The best pharmacophore hypothesis, AAANR, contains chemical features required for the effective inhibition of PHD. Using AAANR, we have identified 18 potential and diverse virtual leads, which can be readily evaluated for their potency as novel inhibitors of PHD. It can be concluded that the combination of pharmacophore, molecular docking, and manual interpretation approaches can be more successful than the traditional approach alone for discovering more effective inhibitors. PMID- 22042610 TI - VCl3 catalyzed imine-based multicomponent reactions for the facile access of functionalized tetrahydropyridines and beta-amino carbonyls. AB - A simple, mild, and highly efficient method has been developed for the preparation of functionalized tetrahydropyridines and beta-amino carbonyls from the multicomponent reactions involving in situ imines and vanadium (III) chloride as a Lewis acid. The multicomponent reaction of two equivalents of aromatic aldehyde, two equivalents of amine, and one equivalent beta-keto ester in the presence of catalytic amount of VCl(3) provides highly atom economic five component tetrahydropyridines in very good yields. The same catalyst was found useful for the efficient synthesis of a wide variety of beta-amino ketones using direct-type Mannich reaction of aromatic aldehyde, amine, and aromatic ketones. The notable advantages of this method are simple procedure, short reaction time and good yields, and applicable to broad range of substrates. PMID- 22042611 TI - Prevention and treatment of alopecia areata with quercetin in the C3H/HeJ mouse model. AB - Alopecia areata (AA) is an autoimmune non-scarring hair loss disorder. AA can be acute, recurrent, or chronic. Current therapeutic options for AA are limited, and there is no effective prevention for recurrent AA. We have previously shown a correlation between the expression of HSP70 (HSPA1A/B), a heat shock protein involved in the inflammatory response, and the onset of AA in the C3H/HeJ mouse model. In this study, we tested the effects of quercetin, a bioflavonoid with anti-inflammatory properties, on AA development and HSP70 expression in the C3H/HeJ model. Mice with spontaneous AA were treated with subcutaneous quercetin or sham injections. Hair regrowth was observed in lesional areas in all the quercetin-treated mice, but in none of the sham-treated mice. In addition, non alopecic C3H/HeJ mice were heat-treated to induce alopecia, along with quercetin or sham injections. Whereas 24% of the heat-treated mice with sham injections developed alopecia, none of the mice receiving quercetin injections did. As expected, the level of HSP70 expression in quercetin-treated areas was comparable to control. Furthermore, we showed that systemic delivery of quercetin by intraperitoneal injections prevented/reduced spontaneous onset of AA. Our results demonstrated that quercetin provided effective treatment for AA as well as prevention of onset of AA in the C3H/HeJ model, and warrant further clinical studies to determine whether quercetin may provide both treatment for preexisting AA and prevention of recurrent AA. The ready availability of quercetin as a dietary supplement may lead to increased patient compliance and positive outcomes for AA. PMID- 22042612 TI - Editorial: LGBT health issues and nursing. PMID- 22042613 TI - California hospitals response to state and federal policies related to health care-associated infections. AB - In October 2008, the Centers for Medicare and Medicaid Services (CMS) denied payment for ten selected health care-associated infections (HAI). In January 2009, California enacted mandatory reporting of infection prevention processes and HAI rates. This longitudinal mixed-methods study examined the impact of federal and state policy changes on California hospitals. Data on structures, processes, and outcomes of care were collected pre- and post-policy changes. In depth interviews with hospital personnel were performed after policy implementation. More than 200 hospitals participated with 25 personnel interviewed. We found significant increases in adoption of and adherence to evidence-based practices and decreased HAI rates (p < .05). Infection preventionists (IP) spent more time on surveillance and in their offices and less time on education and in other locations (p < .05). Qualitative data confirmed mandatory reporting had intended and unintended consequences and highlighted the importance of technology and organizational climate in preventing infections and the changing IPs' role. This is especially relevant because the California Department of Public Health has since mandated hospitals to report data on 29 different for surgical site infections and a lawsuit has been filed to delay the implementation of these requirements. PMID- 22042614 TI - Exploring infection prevention: policy implications from a qualitative study. AB - Health care-associated infections (HAIs) are common and costly patient safety problems that are largely preventable. As a result, numerous policy changes have recently taken place including mandatory reporting and lack of reimbursement for HAIs. A qualitative approach was used to obtain dense description and gain insights about the current practice of infection prevention in California. Twenty three in-depth, semistructured interviews were conducted at six acute care hospitals. Content analysis revealed 4 major interconnected themes: (a) impacts of mandatory reporting; (b) impacts of technology on HAI surveillance; (c) infection preventionists' role expansion; and (d) impacts of organizational climate. Personnel reported that interdisciplinary collaboration was a major facilitator for implementing effective infection prevention, and organizational climate promoting a shared accountability is urgently needed. Mandatory reporting requirements are having both intended and unintended consequences on HAI prevention. More research is needed to measure the long-term effects of these important changes in policy. PMID- 22042615 TI - Comparison of nurse managed health centers with federally qualified health centers as safety net providers. AB - Nurse Managed Health Centers (NMHCs) provide a critical safety net function in their communities, yet they often remain invisible and challenged in terms of financial sustainability. This paper presents a comparison of demographics and financial status of NMHCs and Federally Qualified Health Centers (FQHCs). The comparison is based on four years of annual NMHC national survey data that includes 42 NMHCs overall and the 2008 FQHC data in the Uniform Data System. Findings indicate that NMHCs and FQHCs serve very similar diverse populations yet funding and revenue differences were significant. NMHCs tend to rely more on grants and donations from the private sector as well as contracts while FQHCs have access to considerable federal support that is cost based when serving the underserved. In addition, NMHCs are challenged by the array of state, federal and third party insurers' regulations that often disadvantage nurse practitioners as primary care providers. PMID- 22042616 TI - Benny Geiger: a force in the study of focal adhesions. Interview by Caitlin Sedwick. PMID- 22042617 TI - Impenetrable barriers or entry portals? The role of cell-cell adhesion during infection. AB - Cell-cell adhesion plays a fundamental role in cell polarity and organogenesis. It also contributes to the formation and establishment of physical barriers against microbial infections. However, a large number of pathogens, from viruses to bacteria and parasites, have developed countless strategies to specifically target cell adhesion molecules in order to adhere to and invade epithelial cells, disrupt epithelial integrity, and access deeper tissues for dissemination. The study of all these processes has contributed to the characterization of molecular machineries at the junctions of eukaryotic cells that have been better understood by using pathogens as probes. PMID- 22042618 TI - CIIA functions as a molecular switch for the Rac1-specific GEF activity of SOS1. AB - Son of sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the guanosine triphosphatases Rac1 and Ras, which mediate signaling initiated by peptide growth factors. In this paper, we show that CIIA is a new binding partner of SOS1. CIIA promoted the SOS1-Rac1 interaction and inhibited the SOS1-Ras interaction. Furthermore, CIIA promoted the formation of an SOS1 EPS8 complex and SOS1-mediated Rac1 activation, whereas it inhibited SOS1 mediated activation of Ras. Transforming growth factor beta (TGF-beta) up regulated the expression of CIIA and thereby promoted the association between CIIA and SOS1 in A549 human lung adenocarcinoma cells. Depletion of CIIA in these cells by ribonucleic acid interference inhibited the TGF-beta-induced interaction between SOS1 and EPS8, activation of Rac1, and cell migration. Together, these results suggest that CIIA mediates the TGF-beta-induced activation of SOS1-Rac1 signaling and cell migration in A549 cells. They further show that CIIA functions as a molecular switch for the GEF activity of SOS1, directing this activity toward Rac1. PMID- 22042619 TI - Selective repression of MEF2 activity by PKA-dependent proteolysis of HDAC4. AB - Histone deacetylase 4 (HDAC4) regulates numerous gene expression programs through its signal-dependent repression of myocyte enhancer factor 2 (MEF2) and serum response factor (SRF) transcription factors. In cardiomyocytes, calcium/calmodulin-dependent protein kinase II (CaMKII) signaling promotes hypertrophy and pathological remodeling, at least in part by phosphorylating HDAC4, with consequent stimulation of MEF2 activity. In this paper, we describe a novel mechanism whereby protein kinase A (PKA) overcomes CaMKII-mediated activation of MEF2 by regulated proteolysis of HDAC4. PKA induces the generation of an N-terminal HDAC4 cleavage product (HDAC4-NT). HDAC4-NT selectively inhibits activity of MEF2 but not SRF, thereby antagonizing the prohypertrophic actions of CaMKII signaling without affecting cardiomyocyte survival. Thus, HDAC4 functions as a molecular nexus for the antagonistic actions of the CaMKII and PKA pathways. These findings have implications for understanding the molecular basis of cardioprotection and other cellular processes in which CaMKII and PKA exert opposing effects. PMID- 22042620 TI - Brr6 drives the Schizosaccharomyces pombe spindle pole body nuclear envelope insertion/extrusion cycle. AB - The fission yeast interphase spindle pole body (SPB) is a bipartite structure in which a bulky cytoplasmic domain is separated from a nuclear component by the nuclear envelope. During mitosis, the SPB is incorporated into a fenestra that forms within the envelope during mitotic commitment. Closure of this fenestra during anaphase B/mitotic exit returns the cytoplasmic component to the cytoplasmic face of an intact interphase nuclear envelope. Here we show that Brr6 is transiently recruited to SPBs at both SPB insertion and extrusion. Brr6 is required for both SPB insertion and nuclear envelope integrity during anaphase B/mitotic exit. Genetic interactions with apq12 and defective sterol assimilation suggest that Brr6 may alter envelope composition at SPBs to promote SPB insertion and extrusion. The restriction of the Brr6 domain to eukaryotes that use a polar fenestra in an otherwise closed mitosis suggests a conserved role in fenestration to enable a single microtubule organizing center to nucleate both cytoplasmic and nuclear microtubules on opposing sides of the nuclear envelope. PMID- 22042621 TI - The C terminus of talin links integrins to cell cycle progression. AB - Integrins are cell adhesion receptors that sense the extracellular matrix (ECM) environment. One of their functions is to regulate cell fate decisions, although the question of how integrins initiate intracellular signaling is not fully resolved. In this paper, we examine the role of talin, an adapter protein at cell matrix attachment sites, in outside-in signaling. We used lentiviral small hairpin ribonucleic acid to deplete talin in mammary epithelial cells. These cells still attached to the ECM in an integrin-dependent manner and spread. They had a normal actin cytoskeleton, but vinculin, paxillin, focal adhesion kinase (FAK), and integrin-linked kinase were not recruited to adhesion sites. Talin deficient cells showed proliferation defects, and reexpressing a tail portion of the talin rod, but not its head domain, restored integrin-mediated FAK phosphorylation, suppressed p21 expression, and rescued cell cycle. Thus, talin recruits and activates focal adhesion proteins required for proliferation via the C terminus of its rod domain. Our study reveals a new function for talin, which is to link integrin adhesions with cell cycle progression. PMID- 22042622 TI - Clathrin phosphorylation is required for actin recruitment at sites of bacterial adhesion and internalization. AB - Bacterial pathogens recruit clathrin upon interaction with host surface receptors during infection. Here, using three different infection models, we observed that host-pathogen interactions induce tyrosine phosphorylation of clathrin heavy chain. This modification was critical for recruitment of actin at bacteria-host adhesion sites during bacterial internalization or pedestal formation. At the bacterial interface, clathrin assembled to form coated pits of conventional size. Because such structures cannot internalize large particles such as bacteria, we propose that during infection, clathrin-coated pits serve as platforms to initiate actin rearrangements at bacteria-host adhesion sites. We then showed that the clathrin-actin interdependency is initiated by Dab2 and depends on the presence of clathrin light chain and its actin-binding partner Hip1R, and that the fully assembled machinery can recruit Myosin VI. Together, our study highlights a physiological role for clathrin heavy chain phosphorylation and reinforces the increasingly recognized function of clathrin in actin cytoskeletal organization in mammalian cells. PMID- 22042623 TI - In vitro differentiation and biocompatibility of mesenchymal stem cells on a novel platelet releasate-containing injectable composite. AB - Underlying changes in subchondral and cancellous bone precede joint degeneration in spinal discs, knees, hips, and other joints. We hypothesize that an early bone remodeling intervention therapy may alleviate or postpone the later manifestation of joint failure. Utilization of a novel biomaterial for injection deliverability to the underlying subchondral and cancellous bone during the onset of osseous changes, before severe cartilaginous damage, is proposed. In this preliminary study, we introduced novel platelet releasate-containing alginate/calcium phosphate composites for this intervention therapy and evaluated them in vitro through mesenchymal stem cell biocompatibility and induction of osteochondral differentiation. DNA quantification and gene expression profiles suggested mesenchymal stem cells were directed along an osteochondral differentiation pathway, more specifically, to the immature nonhypertrophic chondrocyte phenotype. These conclusions were based on reduced mitogenic activity, a rapid upregulation followed by suppression of Runx2 transcription factor mRNA, sustained upregulation of Sox9 transcription factor mRNA and the absence of late marker expressions for both mature articular chondrocytes and osteoblasts over the course of 14 days. Initial findings in regard to the use of these materials for bone remodeling were positive and support the execution of future studies evaluating the inflammatory and angiogenic aspects of the materials. In this study, we have considered one of the many aspects of the endochondral ossification process; neovascularization and resorption of bone with an irregular physiology need to be evaluated. PMID- 22042624 TI - Analysis of fluid flow and wall shear stress patterns inside partially filled agitated culture well plates. AB - The appearance of highly resistant bacterial biofilms in both community and hospitals environments is a major challenge in modern clinical medicine. The biofilm structural morphology, believed to be an important factor affecting the behavioral properties of these "super bugs", is strongly influenced by the local hydrodynamics over the microcolonies. Despite the common use of agitated well plates in the biology community, they have been used rather blindly without knowing the flow characteristics and influence of the rotational speed and fluid volume in these containers. The main purpose of this study is to characterize the flow in these high-throughput devices to link local hydrodynamics to observed behavior in cell cultures. In this work, the flow and wall shear stress distribution in six-well culture plates under planar orbital translation is simulated using Computational Fluid Dynamics (CFD). Free surface, flow pattern and wall shear stress for two shaker speeds (100 and 200 rpm) and two volumes of fluid (2 and 4 mL) were investigated. Measurements with a non-intrusive optical shear stress sensor and High Frame-rate Particle Imaging Velocimetry (HFPIV) are used to validate CFD predictions. An analytical model to predict the free surface shape is proposed. Results show a complex three-dimensional flow pattern, varying in both time and space. The distribution of wall shear stress in these culture plates has been related to the topology of flow. This understanding helps explain observed endothelial cell orientation and bacterial biofilm distributions observed in culture dishes. The results suggest that the mean surface stress field is insufficient to capture the underlying dynamics mitigating biological processes. PMID- 22042625 TI - Assessment of material by-product fate from bioresorbable vascular scaffolds. AB - Fully bioresorbable vascular scaffolds (BVS) are attractive platforms for the treatment of ischemic artery disease owing to their intrinsic ability to uncage the treated vessel after the initial scaffolding phase, thereby allowing for the physiological conditioning that is essential to cellular function and vessel healing. Although scaffold erosion confers distinct advantages over permanent endovascular devices, high transient by-product concentrations within the arterial wall could induce inflammatory and immune responses. To better understand these risks, we developed in this study an integrated computational model that characterizes the bulk degradation and by-product fate for a representative BVS composed of poly(L-lactide) (PLLA). Parametric studies were conducted to evaluate the relative impact of PLLA degradation rate, arterial remodeling, and metabolic activity on the local lactic acid (LA) concentration within arterial tissue. The model predicts that both tissue remodeling and PLLA degradation kinetics jointly modulate LA fate and suggests that a synchrony of these processes could minimize transient concentrations within local tissue. Furthermore, simulations indicate that LA metabolism is a relatively poor tissue clearance mechanism compared to convective and diffusive transport processes. Mechanistic understanding of factors governing by-product fate may provide further insights on clinical outcome and facilitate development of future generation scaffolds. PMID- 22042626 TI - Microfluidic platforms for hepatocyte cell culture: new technologies and applications. AB - In this article, we summarize the key elements of microfluidic platforms for mimicking in vivo hepatocyte cell culture and the major recent advances in this area. Specifically, we will give brief background and rationale for key design requirements for mimicking in vivo hepatocyte cell culture, and then summarize findings, applications, and limitations from microfluidic platforms that addressed these design requirements. Although no ideal microfluidic platform has so far been developed for fully mimicking in vivo hepatocyte cell culture, some approaches and designs have demonstrated great potential in this area. PMID- 22042627 TI - Reconstructing the locomotor repertoire of Protopithecus brasiliensis. II. Forelimb morphology. AB - The majority of previous publications have suggested that the large-bodied subfossil Protopithecus brasiliensis was a suspensory ateline with a locomotor repertoire similar to that of extant Ateles and Brachyteles. This is unexpected, as the cranial morphology of Protopithecus is very similar to Alouatta, a genus usually classified as a deliberate quadrupedal climber. Complicating matters further, as Protopithecus is twice as large as Ateles and Brachyteles, its ability to be as suspensory as those two genera is suspect and a terrestrial component of the locomotor repertoire has also been hypothesized. The forelimbs of Protopithecus, while relatively elongated as would be expected in a suspensory animal, are also quite robust and show several adaptations for climbing. To test these hypotheses about the fossil locomotor repertoire, three-dimensional geometric morphometric techniques were used to quantify the shapes of the fossil distal humerus and proximal ulna and then compare them to a broad sample of extant primates with varying body sizes and locomotor patterns. Results indicate that Protopithecus is similar to Ateles and Brachyteles in terms of its forelimb joint surface morphology; however, the overall locomotor repertoire of the fossil is reconstructed as more flexible to include forelimb suspension, climbing, and potentially some terrestrial ground use. The combination of suspensory locomotion and quadrupedal climbing supported here indicates the beginnings of the evolutionary transition from a more acrobatic style of locomotion in the last common ancestor of alouattins and atelins to the current pattern of howler locomotion. PMID- 22042628 TI - Symmetrical peripheral gangrene: a rare presentation of antiphospholipid syndrome. PMID- 22042629 TI - Melanonychia secondary to hydroxyurea. PMID- 22042630 TI - Does a lower diagnostic threshold of sensitive plasma troponin I assay improve clinical outcomes of patients with chest pain? PMID- 22042631 TI - Relative brain size, gut size, and evolution in New World monkeys. AB - The dynamics of brain evolution in New World monkeys are poorly understood. New data on brain weight and body weight from 162 necropsied adult individuals, and a second series on body weight and gut size from 59 individuals, are compared with previously published reports based on smaller samples as well as large databases derived from museum records. We confirm elevated brain sizes for Cebus and Saimiri and also report that Cacajao and Chiropotes have relatively large brains. From more limited data we show that gut size and brain mass have a strongly inverse relationship at the low end of the relative brain size scale but a more diffuse interaction at the upper end, where platyrrhines with relatively high encephalization quotients may have either relatively undifferentiated guts or similar within-gut proportions to low-EQ species. Three of the four main platyrrhine clades exhibit a wide range of relative brain sizes, suggesting each may have differentiated while brains were relatively small and a multiplicity of forces acting to maintain or drive encephalization. Alouatta is a likely candidate for de-encephalization, although its "starting point" is difficult to establish. Factors that may have compelled parallel evolution of relatively large brains in cebids, atelids and pitheciids may involve large social group sizes as well as complex foraging strategies, with both aspects exaggerated in the hyper encephalized Cebus. With diet playing an important role selecting for digestive strategies among the seed-eating pitheciins, comparable in ways to folivores, Chiropotes evolved a relatively larger brain in conjunction with a moderately large and differentiated gut. PMID- 22042632 TI - Second-language experience modulates first- and second-language word frequency effects: evidence from eye movement measures of natural paragraph reading. AB - We used eye movement measures of first-language (L1) and second-language (L2) paragraph reading to investigate whether the degree of current L2 exposure modulates the relative size of L1 and L2 frequency effects (FEs). The results showed that bilinguals displayed larger L2 than L1 FEs during both early- and late-stage eye movement measures, which are taken to reflect initial lexical access and postlexical access, respectively. Moreover, the magnitude of L2 FEs was inversely related to current L2 exposure, such that lower levels of L2 exposure led to larger L2 FEs. In contrast, during early-stage reading measures, bilinguals with higher levels of current L2 exposure showed larger L1 FEs than did bilinguals with lower levels of L2 exposure, suggesting that increased L2 experience modifies the earliest stages of L1 lexical access. Taken together, the findings are consistent with implicit learning accounts (e.g., Monsell, 1991), the weaker links hypothesis (Gollan, Montoya, Cera, Sandoval, Journal of Memory and Language, 58:787-814, 2008), and current bilingual visual word recognition models (e.g., the bilingual interactive activation model plus [BIA+]; Dijkstra & van Heuven, Bilingualism: Language and Cognition, 5:175-197, 2002). Thus, amount of current L2 exposure is a key determinant of FEs and, thus, lexical activation, in both the L1 and L2. PMID- 22042633 TI - Survival processing in times of stress. AB - Recent studies have found that processing information according to an evolutionary relevant (i.e., survival) scenario improves its subsequent memorability, potentially as a result of fitness advantages gained in the ancestral past. So far, research has not revealed much about any proximate mechanisms that might underlie this so-called survival processing advantage in memory. Intriguingly, research has shown that the memorability of stressful situations is enhanced via the release of stress hormones acting on brain regions involved in memory. Since survival situations habitually involve some degree of stress, in the present study, we investigated whether stress serves as a proximate mechanism to promote survival processing. Participants rated words for their relevance to either a survival or a neutral (moving) scenario after they had been exposed to a psychosocial stressor or a no-stress control condition. Surprise retention tests immediately following the rating task revealed that survival processing and acute stress independently boosted memory performance. These results therefore suggest that stress does not serve as a proximate mechanism of the survival processing advantage in memory. PMID- 22042634 TI - Fatal Histoplasma capsulatum mitral endocarditis in a French patient treated for rheumatoid arthritis. AB - Histoplasmosis is an infectious disease caused by the inhalation of Histoplasma capsulatum spores, a fungus encountered in many diverse areas around the world. Although this infection is often asymptomatic, it may become dramatic in immunocompromised patients. In November 2005, an endocarditis due to Histoplasma capsulatum was diagnosed in a French woman treated for rheumatoid arthritis and who had traveled to South America 2 years earlier. We confirmed the biological diagnosis by mycological, serological, and histological methods. In spite of receiving the appropriate treatment, the patient died 3 months later of cardiac insufficiency. We report here this additional case of Histoplasma endocarditis, by hoping to help rapid and accurate diagnosis of such infections in their early stages of development, in non-endemic areas. PMID- 22042635 TI - Antibody-based protein profiling of the human chromosome 21. AB - The Human Proteome Project has been proposed to create a knowledge-based resource based on a systematical mapping of all human proteins, chromosome by chromosome, in a gene-centric manner. With this background, we here describe the systematic analysis of chromosome 21 using an antibody-based approach for protein profiling using both confocal microscopy and immunohistochemistry, complemented with transcript profiling using next generation sequencing data. We also describe a new approach for protein isoform analysis using a combination of antibody-based probing and isoelectric focusing. The analysis has identified several genes on chromosome 21 with no previous evidence on the protein level, and the isoform analysis indicates that a large fraction of human proteins have multiple isoforms. A chromosome-wide matrix is presented with status for all chromosome 21 genes regarding subcellular localization, tissue distribution, and molecular characterization of the corresponding proteins. The path to generate a chromosome specific resource, including integrated data from complementary assay platforms, such as mass spectrometry and gene tagging analysis, is discussed. PMID- 22042636 TI - Plasma omega-3 polyunsaturated fatty acids and survival in patients with chronic heart failure and major depressive disorder. AB - The omega-3 fatty acid (FA) concentration is low in patients with coronary heart disease (CHD). Supplement of omega-3 FA improves cardiovascular outcomes in patients with CHD and heart failure (HF). However, plasma omega-3 FA and its role for prognosis in HF patients have not been examined previously. In this study, we explore the prognostic value of omega-3 polyunsaturated FA in HF patients with major depressive disorder (MDD). Plasma was obtained from HF patients with MDD who participated in the Sertraline Against Depression and Heart Disease in Chronic Heart Failure trial. FA methyl esters were analyzed by the method of a flame ionization detector. Weight percent is the unit of the omega compounds. The primary outcome was survival which was analyzed using Cox proportional hazards regression modeling. A total of 109 depressed HF patients had adequate volume for completion of the FA assays. Plasma total omega-3 (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.43-0.98) and EPA_(0.1 unit) (HR 0.73, 95% CI 0.56 0.96) were significantly associated with survival of patients with HF and co morbid MDD. The results suggest that low plasma omega-3 FA is a significant factor for reduced survival in HF patients with MDD. PMID- 22042637 TI - Routine invasive versus conservative management in non-ST-elevation acute coronary syndromes. AB - Coronary angiography as part of the management of non-ST-segment-elevation acute coronary syndrome (ACS) patients has several advantages but also carries some risks if done routinely. The advantage of a planned early invasive approach in moderate to high-risk patients appears to be clear and is recommended by guidelines. This is often not mirrored by real world practice; however, only about 50% to 70% of ACS patients do undergo a diagnostic catheterization. In addition, the optimal timing of an angiography or intervention in relation to contemporary antithrombotic regimens remains unclear. In this paper, the current evidence for routine invasive management as well as the timing of catheterization in non-ST-ACS is reviewed. PMID- 22042638 TI - Improving the sensitivity of immunoassays with PEG-COOH-like film prepared by plasma-based technique. AB - Herein we report on a preparation and performance of stable, hydrophilic and biocompatible polymeric material suitable for functionalization of disposable substrates used in biosensors. This new material features ?COOH surface groups cross-linked with ethylene glycol molecules and was prepared in situ on disposable, plastic substrate by high-throughput and environmentally friendly technique called plasma-enhanced chemical vapor deposition (PECVD). The film is grafted to the plasma activated plastic by sequential deposition of tetraethylorthosilicate, forming a bonding layer, and mixed vapors of acrylic acid and diethyleneglycol dimethylether (AA/PEG) that provide the desired functional groups forming a sensing, contact layer. A superior performance of the AA/PEG coating as suitable material for substrates in biomedical devices was demonstrated in a model fluorescence linked immunosorbent assay. The results were compared with other commonly used surface materials prepared by wet chemistry methods. The unique characteristic of the AA/PEG film is that the immunoassay can be executed without the need for a blocking step, typically using albumins, without negative consequences on the bioassay results. In fact, the superior quality of the materials modified with AA/PEG film was highlighted by improving the sensitivity of an immunoassay by two orders of magnitude when compared with substrates prepared by standard surface chemistry methods. PMID- 22042640 TI - Craniofacial adaptations to tree-gouging among marmosets. AB - Many primates rely on exudates as dietary items, but comparatively few elicit exudates via tree-gouging. Marmosets are the only haplorhines to extensively utilize this behavior during feeding. Several studies have explored craniofacial adaptations to this behavior, but its morphological correlates are a matter of debate. Various studies suggest that gougers exhibit bite-force maximizing adaptations, load resistance adaptations, and/or jaw-gape maximizing characteristics. All of these seemingly incompatible biomechanical adaptations have previously been argued for marmosets. This study utilizes multivariate and univariate analyses to compare gouging and non-gouging callitrichids for 25 biomechanically relevant craniofacial variables to address this form-function debate. We show that marmosets differ from non-gouging callitrichids in few craniofacial characteristics. Specifically, three craniofacial features differentiate them from non-gougers: relatively longer basicrania, narrower palates, and shorter coronoid processes. We suggest that these characteristics are consistent with a mosaic model for gouging adaptations. In particular, we argue that: (a) shortening the coronoid processes facilitates relatively larger maximum jaw-gapes, (b) basicranial elongation facilitates the extended neck/head posture utilized by marmosets during gouging to maximize gapes, and (c) narrowing the palate serves to more effectively dissipate forces through the maxillary canines during substrate anchoring. Previous studies have documented some of these characters as typical of marmosets, but this combination has not been interpreted as core elements of the marmoset adaptive complex. Marmosets exhibit a unique anatomical repertoire that biomechanically adapts them to both increased jaw-gape and the force dissipation regime associated with tree-gouging. Comparisons among marmoset taxa may enlighten the evolutionary history of the features reported here. PMID- 22042641 TI - Tissue distribution of alpha- and gamma-tocotrienol and gamma-tocopherol in rats and interference with their accumulation by alpha-tocopherol. AB - The aim of this study was to evaluate tissue distribution of vitamin E isoforms such as alpha- and gamma-tocotrienol and gamma-tocopherol and interference with their tissue accumulation by alpha-tocopherol. Rats were fed a diet containing a tocotrienol mixture or gamma-tocopherol with or without alpha-tocopherol, or were administered by gavage an emulsion containing tocotrienol mixture or gamma tocopherol with or without alpha-tocopherol. There were high levels of alpha tocotrienol in the adipose tissue and adrenal gland, gamma-tocotrienol in the adipose tissue, and gamma-tocopherol in the adrenal gland of rats fed tocotrienol mixture or gamma-tocopherol for 7 weeks. Dietary alpha-tocopherol decreased the alpha-tocotrienol and gamma-tocopherol but not gamma-tocotrienol concentrations in tissues. In the oral administration study, both tocopherol and tocotrienol quickly accumulated in the adrenal gland; however, their accumulation in adipose tissue was slow. In contrast to the dietary intake, alpha-tocopherol, which has the highest affinity for alpha-tocopherol transfer protein (alphaTTP), inhibited uptake of gamma-tocotrienol to tissues including adipose tissue after oral administration, suggesting that the affinities of tocopherol and tocotrienol for alphaTTP in the liver were the critical determinants of their uptake to peripheral tissues. Vitamin E deficiency for 4 weeks depleted tocopherol and tocotrienol stores in the liver but not in adipose tissue. These results indicate that dietary vitamin E slowly accumulates in adipose tissue but the levels are kept without degradation. The property of adipose tissue as vitamin E store causes adipose tissue-specific accumulation of dietary tocotrienol. PMID- 22042642 TI - Locus- and domain-dependent control of DNA methylation at mouse B1 retrotransposons during male germ cell development. AB - In mammals, germ cells undergo striking dynamic changes in DNA methylation during their development. However, the dynamics and mode of methylation are poorly understood for short interspersed elements (SINEs) dispersed throughout the genome. We investigated the DNA methylation status of mouse B1 SINEs in male germ cells at different developmental stages. B1 elements showed a large locus-to locus variation in methylation; loci close to RNA polymerase II promoters were hypomethylated, while most others were hypermethylated. Interestingly, a mutation that eliminates Piwi-interacting RNAs (piRNAs), which are involved in methylation of long interspersed elements (LINEs), did not affect the level of B1 methylation, implying a piRNA-independent mechanism. Methylation at B1 loci in SINE-poor genomic domains showed a higher dependency on the de novo DNA methyltransferase DNMT3A but not on DNMT3B, suggesting that DNMT3A plays a major role in methylation of these domains. We also found that many genes specifically expressed in the testis possess B1 elements in their promoters, suggesting the involvement of B1 methylation in transcriptional regulation. Taken altogether, our results not only reveal the dynamics and mode of SINE methylation but also suggest how the DNA methylation profile is created in the germline by a pair of DNA methyltransferases. PMID- 22042643 TI - Deep-transcriptome and ribonome sequencing redefines the molecular networks of pluripotency and the extracellular space in human embryonic stem cells. AB - Recent RNA-sequencing studies have shown remarkable complexity in the mammalian transcriptome. The ultimate impact of this complexity on the predicted proteomic output is less well defined. We have undertaken strand-specific RNA sequencing of multiple cellular RNA fractions (>20 Gb) to uncover the transcriptional complexity of human embryonic stem cells (hESCs). We have shown that human embryonic stem (ES) cells display a high degree of transcriptional diversity, with more than half of active genes generating RNAs that differ from conventional gene models. We found evidence that more than 1000 genes express long 5' and/or extended 3'UTRs, which was confirmed by "virtual Northern" analysis. Exhaustive sequencing of the membrane-polysome and cytosolic/untranslated fractions of hESCs was used to identify RNAs encoding peptides destined for secretion and the extracellular space and to demonstrate preferential selection of transcription complexity for translation in vitro. The impact of this newly defined complexity on known gene-centric network models such as the Plurinet and the cell surface signaling machinery in human ES cells revealed a significant expansion of known transcript isoforms at play, many predicting possible alternative functions based on sequence alterations within key functional domains. PMID- 22042644 TI - Biological and therapeutic applications of small RNAs. PMID- 22042645 TI - Hybrid modeling framework for process analytical technology: application to Bordetella pertussis cultures. AB - In the process analytical technology (PAT) initiative, the application of sensors technology and modeling methods is promoted. The emphasis is on Quality by Design, online monitoring, and closed-loop control with the general aim of building in product quality into manufacturing operations. As a result, online high-throughput process analyzers find increasing application and therewith high amounts of highly correlated data become available online. In this study, an hybrid chemometric/mathematical modeling method is adopted for data analysis, which is shown to be advantageous over the commonly used chemometric techniques in PAT applications. This methodology was applied to the analysis of process data of Bordetella pertussis cultivations, namely online data of near-infrared, (NIR), pH, temperature and dissolved oxygen, and off-line data of biomass, glutamate, and lactate concentrations. The hybrid model structure consisted of macroscopic material balance equations in which the specific reactions rates are modeled by nonlinear partial least square (PLS). This methodology revealed a significant higher statistical confidence in comparison to PLSs, translated in a reduction of mean squared prediction errors (e.g., individual root mean squared prediction errors calibration/validation obtained through the hybrid model for the concentrations of lactate: 0.8699/0.7190 mmol/L; glutamate: 0.6057/0.2917 mmol/L; and biomass: 0.0520/0.0283 OD; and obtained through the PLS model for the concentrations of lactate: 1.3549/1.0087 mmol/L; glutamate: 0.7628/0.3504 mmol/L; and biomass: 0.0949/0.0412 OD). Moreover, the analysis of loadings and scores in the hybrid approach revealed that process features can, as for PLS, be extracted by the hybrid method. PMID- 22042646 TI - Affective norms for 380 Spanish words belonging to three different semantic categories. AB - Emotional words are increasingly used in the study of word processing. To elucidate whether the experimental effects obtained with these words are due either to their affective content or to other semantic characteristics, it is necessary to conduct experiments with affectively valenced words obtained from different semantic categories. In the present article, we present affective ratings for 380 Spanish words belonging to three semantic categories: animals, people, and objects. The norms are based on the assessments made by 504 participants, who rated about 47 words either in valence and arousal, by using the Self-Assessment Manikin (Bradley & Lang, Journal of Behavioral Therapy and Experimental Psychiatry, 25, 49-59. 1994), or in concreteness and familiarity. These ratings will help researchers select stimuli for experiments in which both the affective properties of words and their membership to a given semantic category have to be taken into account. The database is available as an online supplement for this article. PMID- 22042647 TI - Primary intraosseous cavernous hemangioma of the toe. AB - Intraosseous cavernous hemangioma is an uncommon benign vascular tumor. A 21-year old man presented with a small painless swelling of the left foot's long toe. X ray examination showed an outgrowing bony lesion that has cortical continuity in the tip of the long toe's distal phalanx lateral aspect. Preoperative examination yielded no final diagnosis. En bloc resection was performed. The histological diagnosis was intraosseous cavernous hemangioma. To the best of our knowledge, this case is a first report of primary intraosseous cavernous hemangioma of the toe. PMID- 22042648 TI - Isolated rupture of biceps femoris tendon. AB - Authors present a case of rupture of the distal end of the biceps femoris. Injuries at this site are relatively rare. Clinical assessment can be aided by instrumental examinations such as ultrasound and especially NMR. Delayed treatment because of erroneous diagnosis or failure of conservative therapy can result in proximal retraction and atrophy of the muscle belly, requiring more complex surgery. Despite the limited data in the literature, Authors favor immediate surgical treatment of both complete and partial injury of the biceps femoris tendon, particularly in a patient who requires a high level of function. PMID- 22042649 TI - Sustained release of neurotrophin-3 and chondroitinase ABC from electrospun collagen nanofiber scaffold for spinal cord injury repair. AB - Nerve regeneration after spinal cord injuries (SCI) remains suboptimal despite recent advances in the field. One major hurdle is the rapid clearance of drugs from the injury site, which greatly limits therapeutic outcomes. Nanofiber scaffolds represent a potential class of materials for enhancing nerve regeneration because of its biomimicking architecture. In this study, we investigated the feasibility of incorporating neurotrophin-3 (NT-3) and chondroitinase ABC (ChABC) onto electrospun collagen nanofibers for SCI treatment. By using microbial transglutaminase (mTG) mediated crosslinking, proteins were loaded onto electrospun collagen nanofibers at an efficiency of ~45 48%. By combining NT-3 with heparin during the protein incorporation process, a sustained release of NT-3 was obtained (~96% by day 28). As indicated by dorsal root ganglion outgrowth assay, NT-3 incorporated collagen scaffolds supported neuronal culture and neurite outgrowth for a longer time period than bolus delivery of NT-3. The presence of heparin also protected ChABC from degradation. Specifically, as evaluated by dimethylmethylene blue assay, bioactive ChABC was detected from collagen scaffolds for at least 32 days in vitro in the presence of heparin (~32% of bioactivity retained). In contrast, ChABC bioactivity was only ~1.9% by day 22 in the absence of heparin. Taken together, these results clearly demonstrated the feasibility of incorporating NT-3 and ChABC via mTG immobilization to produce protein-incorporated collagen nanofibers. Such biofunctional nanofiber constructs may find useful applications in SCI treatment by providing topographical signals and multiple biochemical cues that can promote nerve regeneration while antagonizing axonal growth inhibition for CNS regeneration. PMID- 22042650 TI - Comment on the paper "indexing molecules with chemical graph identifiers" by Elisabeth Gregori-Puigjane, Rut Garriga-Sust, and Jordi Mestres. PMID- 22042651 TI - Effect of epidermal growth factor on follicle-stimulating hormone-induced proliferation of granulosa cells from chicken prehierarchical follicles. AB - The development of ovarian follicular cells is controlled by multiple circulating and local hormones and factors, including follicle-stimulating hormone (FSH) and epidermal growth factor (EGF). In this study, the stage-specific effect of EGF on FSH-induced proliferation of granulosa cells was evaluated in the ovarian follicles of egg-laying chickens. Results showed that EGF and its receptor (EGFR) mRNAs displayed a high expression in granulosa cells from the prehierarchical follicles, including the large white follicle (LWF) and small yellow follicle (SYF), and thereafter the expression decreased markedly to the stage of the largest preovulatory follicle. SYF represents a turning point of EGF/EGFR mRNA expression during follicle selection. Subsequently the granulosa cells from SYF were cultured to reveal the mediation of EGF in FSH action. Cell proliferation was remarkably increased by treatment with either EGF or FSH (0.1-100 ng/ml). This result was confirmed by elevated proliferating cell nuclear antigen (PCNA) expression and decreased cell apoptosis. Furthermore, EGF-induced cell proliferation was accompanied by increased mRNA expressions of EGFR, FSH receptor, and the cell cycle-regulating genes (cyclins D1 and E1, cyclin dependent kinases 2 and 6) as well as decreased expression of luteinizing hormone receptor mRNA. However, the EGF or FSH-elicited effect was reversed by simultaneous treatment with an EGFR inhibitor AG1478. In conclusion, EGF and EGFR expressions manifested stage-specific changes during follicular development and EGF mediated FSH-induced cell proliferation and retarded cell differentiation in the prehierarchical follicles. These expressions thus stimulated follicular growth before selection in the egg-laying chicken. PMID- 22042652 TI - Development of an indirect competitive ELISA for simultaneous detection of enrofloxacin and ciprofloxacin. AB - Modified 1-ethyl-3-(3-dimethylaminopropy) carbodiimide (EDC) method was employed to synthesize the artificial antigen of enrofloxacin (ENR), and New Zealand rabbits were used to produce anti-ENR polyclonal antibody (pAb). Based on the checkerboard titration, an indirect competitive enzyme-linked immunosorbent assay (ELISA) standard curve was established. This assay was sensitive and had a linear range from 0.6 to 148.0 MUg/kg (R(2) = 0.9567), with the half maximal inhibitory concentration (IC(50)) and limit of detection (LOD) values of 9.4 MUg/kg and 0.2 MUg/kg, respectively. Of all the competitive analogues, the produced pAb exhibited a high cross-reactivity to ciprofloxacin (CIP) (87%), the main metabolite of ENR in tissues. After optimization, the matrix effects can be ignored using a 10-fold dilution in beef and 20-fold dilution in pork. The overall recoveries and coefficients of variation (CVs) were in the ranges of 86% 109% and 6.8%-13.1%, respectively. It can be concluded that the established ELISA method is suitable for simultaneous detection of ENR and CIP in animal tissues. PMID- 22042653 TI - Effect of quantum therapy on pork quality. AB - In this study the impact of quantum therapy on meat quality of slaughtered pigs was investigated. For this purpose the pigs were treated with different doses of magnet-infrared-laser (MIL) radiation. Animals were divided into four groups according to radiation doses (4096, 512, and 64 Hz, and control without application), which were applied in the lumbar area of musculus longissimus dorsi (loin) at various time intervals prior to the slaughter (14 d, 24 h, and 1 h). Animals were slaughtered and the meat quality was evaluated by determining of pH value (1, 3, and 24 h post slaughter), drip loss, colour, and lactic acid and phosphoric acid amounts. MIL therapy can be used in various fields of veterinary medicine as are surgery and orthopaedics, internal medicine, dentistry, pulmonology, gastroenterology, gynaecology, urology, nephrology, and dermatology. The results achieved showed that MIL radiation used in a short period before slaughter (1 h) can cause a change in the meat quality, as reflected by the non standard development of pH values, increases in drip loss, and changes of meat colour. PMID- 22042654 TI - Involvement of basolateral amygdala GABAA receptors in the effect of dexamethasone on memory in rats. AB - In this study we investigated whether GABA(A) receptors of the basolateral amygdala (BLA) interact with the effect of dexamethasone on the retrieval stage of memory. Adult male Wistar rats were bilaterally cannulated in the BLA by stereotaxic surgery. The animals were trained in step-through apparatus by induction of electric shock (1.5 mA, 3 s) and were tested for memory retrieval after 1 d. The time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance memory. Administration of dexamethasone (0.3 and 0.9 mg/kg, subcutaneously (s.c.)), immediately after training, enhanced memory retrieval. This effect was reduced by intra-BLA microinjection of muscimol (0.125, 0.250 and 0.500 ug/rat), when administered before 0.9 mg/kg of dexamethasone. Microinjection of bicuculline (0.75 ug/rat, intra-BLA) with an ineffective dose of dexamethasone (0.1 mg/kg, s.c.) increased memory retrieval. However, the same doses of muscimol and bicuculline without dexamethasone did not affect memory processes. Our data support reports that dexamethasone enhances memory retrieval. It seems that GABA(A) receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats. PMID- 22042655 TI - Growth rate, catalase and superoxide dismutase activities in rock carp (Procypris rabaudi Tchang) exposed to supersaturated total dissolved gas. AB - Total dissolved gas supersaturation (TDGS) appears when the pressures of gases in a solution exceed the barometric pressures. TDGS is often caused by flood discharge at dams. It may lead to gas bubble disease (GBD) for fish and biochemical responses of selected fish and other aquatic organisms. The purpose of this study was to determine the impact of long-term TDGS levels on the growth and biochemical responses of rock carp (Procypris rabaudi Tchang) dwelling in the upper reaches of the Yangtze River. Three-year-old rock carp were exposed to TDGS levels at 100%, 104%, 108%, 112%, and 116% for 42 d. Samples were taken every 7 d after the start of the trial in order to determine catalase (CAT) and superoxide dismutase (SOD) activities in gill and muscle tissues. Samples were taken at Days 0 and 42 of exposure to determine growth rate. Little effect was found on growth rate in all treatment groups. SOD and CAT activities varied in different tissues, according to time of exposure and TDGS levels. The biochemical response of fish exposed to TDGS was more obvious in gill tissue than in muscle tissue. Surveys of SOD and CAT activities in different tissues offer important information about the effect of TDGS on the rare fish in the Yangtze River, and may help evaluate the risk to the aquatic eco-environment and aquatic ecosystem in the downstream of the Yangtze River. PMID- 22042656 TI - Antioxidants in aqueous extract of Myristica fragrans (Houtt.) suppress mitosis and cyclophosphamide-induced chromosomal aberrations in Allium cepa L. cells. AB - In this study, freeze-dried water extract from the leaves of Myristica fragrans (Houtt.) was tested for mutagenic and antimutagenic potentials using the Allium cepa assay. Freeze-dried water extract alone and its combination with cyclophosphamide (CP) (50 mg/kg) were separately dissolved in tap water at 500, 1000, 2000, and 4000 mg/kg. Onions (A. cepa) were suspended in the solutions and controls for 48 h in the dark. Root tips were prepared for microscopic evaluation. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radicals' scavenging power of the extract was tested using butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as standards. Water extract of Myristica fragrans scavenged free radicals better than BHA, but worse than BHT. The extract alone, as well as in combination with CP suppressed cell division, and induced chromosomal aberrations that were insignificantly different from the negative control (P <= 0.05). However, cytotoxic and mutagenic actions of CP were considerably suppressed. The observed effects on cell division and chromosomes of A. cepa may be principally connected to the antioxidant properties of the extract. The obtained results suggest mitodepressive and antimutagenic potentials of water extract of the leaves of M. fragrans as desirable properties of a promising anticancer agent. PMID- 22042657 TI - Production of conjugated linoleic acids by Lactobacillus plantarum strains isolated from naturally fermented Chinese pickles. AB - Naturally fermented pickles harbour many lactic acid bacteria (LAB). Forty-three LAB strains with conjugated linoleic acid (CLA)-producing ability were isolated from three naturally fermented pickle brines. Of these isolates, lp15 identified as Lactobacillus plantarum by API 50 CHL system and full-length 16S rDNA sequence analysis exhibited the highest CLA-producing ability (26.1% conversion) at 48 h in de Man Rogosa Sharpe (MRS) broth in the presence of 100 ug/ml of linoleic acid (LA). Compared to other strains, L. plantarum strain lp15 showed the highest tolerance upon increased levels of LA in the medium, i.e., up to 600 ug/ml. This strain converted about 25% of LA into CLA isomers [predominantly cis-9, trans-11 CLA (9-CLA) and trans-10, cis-12 CLA (10-CLA)], of which 75% was 9-CLA. Interestingly, though the conversion rate of LA into CLA by lp15 remained stable between 100 to 600 ug/ml LA levels in the medium, it dropped sharply at 1000 ug/ml. Taken together, the lp15 strain displayed relatively high LA tolerance with higher conversion rate, which implies that this strain is a valuable candidate for enhancing the CLA content in food-sources like pickles. PMID- 22042658 TI - Preparation of glucosamine by hydrolysis of chitosan with commercial alpha amylase and glucoamylase. AB - OBJECTIVE: In order to overcome the defects of chemical hydrolysis approach to prepare glucosamine, an enzymatic hydrolysis method was developed. METHODS: Glucosamine was prepared by hydrolyzing chitosan, employing alpha-amylase initially, and subsequently, glucoamylase. RESULTS: The optimal hydrolyzing conditions were as follows: reaction time, 4 h; pH, 5.0; temperature, 50 degrees C; and, alpha-amylase, 80 U/g for the initial reaction. Subsequently, glucoamylase was added in the presence of alpha-amylase. The optimal reaction conditions were found to be: reaction time, 8 h; pH, 4.5; temperature, 55 degrees C; and, glucoamylase, 4000 U/g. The hydrolysates were subject to filtrating, concentrating to about 20% (w/w), precipitating with five volumes of ethanol, and drying at 60 degrees C for 2 h. The content and the yield of glucosamine in the dried precipitate were 91.3% (w/w) and 86.2% (w/w), respectively. CONCLUSIONS: The method developed in this study is a promising option in the preparation of glucosamine. PMID- 22042659 TI - DNA methylation polymorphism in flue-cured tobacco and candidate markers for tobacco mosaic virus resistance. AB - DNA methylation plays an important role in the epigenetic regulation of gene expression during plant growth, development, and polyploidization. However, there is still no distinct evidence in tobacco regarding the distribution of the methylation pattern and whether it contributes to qualitative characteristics. We studied the levels and patterns of methylation polymorphism at CCGG sites in 48 accessions of allotetraploid flue-cured tobacco, Nicotiana tabacum, using a methylation-sensitive amplified polymorphism (MSAP) technique. The results showed that methylation existed at a high level among tobacco accessions, among which 49.3% sites were methylated and 69.9% allelic sites were polymorphic. A cluster analysis revealed distinct patterns of geography-specific groups. In addition, three polymorphic sites significantly related to tobacco mosaic virus (TMV) resistance were explored. This suggests that tobacco breeders should pay more attention to epigenetic traits. PMID- 22042660 TI - A recessive gene controlling male sterility sensitive to short daylength/low temperature in wheat (Triticum aestivum L.). AB - Utilization of a two-line breeding system via photoperiod-thermo sensitive male sterility has a great potential for hybrid production in wheat (Triticum aestivum L.). 337S is a novel wheat male sterile line sensitive to both short daylength/low temperature and long daylength/high temperature. Five F(2) populations derived from the crosses between 337S and five common wheat varieties were developed for genetic analysis. All F(1)'s were highly fertile while segregation occurred in the F(2) populations with a ratio of 3 fertile:1 sterile under short daylength/low temperature. It is shown that male sterility in 337S was controlled by a single recessive gene, temporarily designated as wptms3. Bulked segregant analysis (BSA) coupled with simple sequence repeat (SSR) markers was applied to map the sterile gene using one mapping population. The wptms3 gene was mapped to chromosome arm 1BS and flanked by Xgwm413 and Xgwm182 at a genetic distance of 3.2 and 23.5 cM, respectively. The accuracy and efficiency of marker assisted selection were evaluated and proved essential for identifying homozygous recessive male sterile genotypes of the wptms3 gene in F(2) generation. PMID- 22042663 TI - Reconstructing the locomotor repertoire of Protopithecus brasiliensis. I. Body size. AB - An accurate body size estimate is essential for reconstructing and interpreting many aspects of the paleobiology of an extinct taxon. With this in mind, the purpose of this study is two-fold: first, to create statistically robust predictive regression equations for body mass, total body length, and head and body length from postcranial elements using a platyrrhine reference sample, data that do not exist elsewhere in the literature; and, second, to apply those regression equations to the "giant" subfossil platyrrhine Protopithecus brasiliensis, a little-studied taxon represented by a nearly complete skeleton. Building on results of previous work with other primate groups, different skeletal elements, subgroups of the reference sample, and regression models lead to different body size estimates with different standard errors and prediction errors. However, relatively tight clusters of estimates around 20 kg, total length of 1,675 mm, and head and body length of 710 mm are obtained, placing the fossil in the size range of a large male baboon. While not quite as large as the original 25 kg body mass estimate for the fossil, this new estimate is still approximately 150% larger than the largest living New World monkey. Confirmation of its place in a large-bodied size class of platyrrhines has a profound effect on reconstructing the locomotor repertoire of Protopithecus and the evolutionary trajectory of the alouattin lineage. PMID- 22042662 TI - Work ability of survivors of breast, prostate, and testicular cancer in Nordic countries: a NOCWO study. AB - INTRODUCTION: Cancer can cause adverse effects on survivors' work ability. We compared the self-assessed work ability of breast, testicular, and prostate cancer survivors to that of people without cancer. We also investigated the association of disease-related and socio-demographic factors and job-related resources (organizational climate, social support, and avoidance behavior) with work ability and looked at whether these associations were different for the survivors and reference subjects. METHODS: Working aged cancer patients diagnosed between 1997 and 2002 were identified from hospital or cancer registries in Denmark, Finland, Iceland, and Norway (Nordic Study on Cancer and Work). A cancer free reference group was selected from population registries. We collected information on work ability and other factors from 1,490 employed survivors and 2,796 reference subjects via a questionnaire. RESULTS: The adjusted mean value of work ability was slightly lower among the breast and prostate cancer survivors compared to the cancer-free population. Co-morbidity, chemotherapy, low workplace support, and low organizational commitment were associated with reduced work ability. Avoidance behavior from supervisors or colleagues was only related to work ability among the cancer survivors. CONCLUSIONS AND IMPLICATIONS: More attention should be paid to assisting cancer survivors in work life, particularly those who have chronic diseases or have undergone chemotherapy. Although most factors affecting the work ability of the survivors and reference subjects were the same, survivors' work ability seemed to be particularly sensitive to avoidance behavior. The results suggest that there is a need to improve communication at the workplace and develop supportive leadership practices in order to avoid isolating behavior towards cancer survivors. PMID- 22042661 TI - How confident are young adult cancer survivors in managing their survivorship care? A report from the LIVESTRONGTM Survivorship Center of Excellence Network. AB - INTRODUCTION: This study examined the association between sociodemographic, cancer treatment, and care delivery factors on young adult cancer survivors' confidence in managing their survivorship care. METHODS: Survivors aged 18-39 years (n = 376) recruited from the LIVESTRONGTM Survivorship Center of Excellence Network sites completed a survey assessing self-reported receipt of survivorship care planning, expectations of their providers, and confidence in managing their survivorship care. Multivariate logistic regression identified characteristics of those reporting low confidence in managing their survivorship care. RESULTS: Mean age was 28 years; mean interval from diagnosis was 9 +/- 8 years. Seventy-one percent reported currently attending an oncology survivorship clinic. Regarding survivorship care planning, 33% did not have copies of their cancer-related medical records, 48% did not have a treatment summary, and 55% had not received a survivorship care plan. Seventy percent identified the oncologist as the most important health care provider for decisions regarding test and treatment decisions while 10% reported using a "shared-care model" involving both primary care providers and oncologists. Forty-one percent were classified as having low confidence in managing survivorship care. In multivariate analysis, low confidence was associated with non-white ethnicity and lack of a survivorship care plan (both p < 0.05). DISCUSSION/CONCLUSIONS: Findings suggest that provision of survivorship care plans for young adult cancer survivors can be used to improve confidence in managing survivorship care, particularly for ethnic minorities. IMPLICATIONS FOR CANCER SURVIVORS: Survivors should consider advocating for receipt of a survivorship care plan as it may facilitate confidence as a consumer of survivorship care. PMID- 22042664 TI - Differential survival in Europe and the United States: estimates based on subjective probabilities of survival. AB - Cross-country comparisons of differential survival by socioeconomic status (SES) are useful in many domains. Yet, to date, such studies have been rare. Reliably estimating differential survival in a single country has been challenging because it requires rich panel data with a large sample size. Cross-country estimates have proven even more difficult because the measures of SES need to be comparable internationally. We present an alternative method for acquiring information on differential survival by SES. Rather than using observations of actual survival, we relate individuals' subjective probabilities of survival to SES variables in cross section. To show that subjective survival probabilities are informative proxies for actual survival when estimating differential survival, we compare estimates of differential survival based on actual survival with estimates based on subjective probabilities of survival for the same sample. The results are remarkably similar. We then use this approach to compare differential survival by SES for 10 European countries and the United States. Wealthier people have higher survival probabilities than those who are less wealthy, but the strength of the association differs across countries. Nations with a smaller gradient appear to be Belgium, France, and Italy, while the United States, England, and Sweden appear to have a larger gradient. PMID- 22042665 TI - The apparent voltage dependence of GABAA receptor activation and modulation is inversely related to channel open probability. AB - The GABA type A receptor (GABA(A)R) is expressed ubiquitously throughout the brain and is a target for many therapeutic agents, including general anesthetics and benzodiazepines, which enhance receptor function by increasing the open probability (P(o)) of the ion channel. It is commonplace for in vitro studies of receptor pharmacological characteristics to use negative membrane holding potentials to mimic the resting potential of neurons and symmetrical chloride to eliminate Goldman rectification, which results in chloride flow in the opposite direction, compared with in vivo conditions. This critical difference is usually overlooked because the GABA(A)R has been reported to behave as an ohmic pore, but our results show that the current-voltage relationship is nonlinear with respect to P(o). Specifically, we found that currents were outwardly rectifying at low P(o) and linear at high P(o). We confirmed the correlation between P(o) and rectification with a partial agonist, piperidine-4-sulfonic acid, and a gating impaired mutation, alpha1(L277A); both exhibited enhanced outward rectification. Furthermore, this correlation was independent of Goldman rectification and persisted under altered chloride gradient conditions, which suggests that rectification is linked to the direction of chloride flux. Finally, our results showed that the degree of potentiation by general anesthetics (etomidate, propofol, and isoflurane) was greater at negative membrane potentials. Traditional in vitro experiments thus overestimate the action of positive allosteric modulators of the GABA(A)R. Our results show that the direction of the driving force on the permeant ion, as well as P(o), must be considered together for a complete understanding of drug actions on ligand-gated ion channels. PMID- 22042666 TI - Managing two cultural identities: the malleability of bicultural identity integration as a function of induced global or local processing. AB - Increasingly, individuals identify with two or more cultures. Prior research has found the degree to which individuals chronically integrate these identities (bicultural identity integration; BII) moderates responses to cultural cues: High BII individuals assimilate (adopting biases that are congruent with norms of the cued culture), whereas low BII individuals contrast (adopting biases that are incongruent with these norms). The authors propose BII can also be a psychological state and modulated by shifts in processing styles. In four experiments, the authors induced a global or local processing style using physical posture (Experiment 1) and cognitive manipulations (Experiments 2-4) and found that BII is enhanced in contexts facilitating a more global processing style (i.e., smiling, high-level construal, and similarity focus). The authors also found that contrastive responses to cultural cues are diminished when BII is situationally enhanced. Implications for research on processing style, identity integration, and performance in culture-based situations are discussed. PMID- 22042667 TI - Stigma building blocks: how instruction and experience teach children about rejection by outgroups. AB - Gaining an understanding of intergroup relations and outgroup rejection is an important childhood development. Children learn about rejection by outgroups via their own experiences and external instruction. A comparison of the impact of experience and instruction on first-, third-, and fifth-grade children's evaluations of rejection by outgroups in a minimal-groups paradigm suggests that the relative impact of experience and instruction differs as children age. In Study 1, younger children were more influenced by instruction, and older children were more influenced by what they experienced for themselves. In Study 2, younger children were more influenced by instruction, even when that instruction conflicted with what they experienced; older children were more influenced by their own experiences, even when those experiences contradicted what they were told to expect. These findings suggest that children begin learning about outgroup rejection through instruction but start to rely more on their own experiences as they age. PMID- 22042668 TI - Planning and monitoring of patients for electrical cardioversion for atrial fibrillation. AB - OBJECTIVES: This study evaluated the waiting list for elective electrical cardioversion (ECV) for persistent atrial fibrillation (AF), focusing on when and why procedures were postponed. We compared the effects of management of the waiting list conducted by physicians versus management by nurse practitioners (NPs) and we evaluated the safety of our anticoagulating policy by means of bleeding or thromboembolic complications during and after ECV. BACKGROUND: Not all patients selected for ECV receive their treatment at the first planned instance due to a variety of reasons. These reasons are still undocumented. METHODS: We evaluated 250 consecutive patients with persistent AF admitted to our clinic for elective ECV. RESULTS: Within 5 to 6 weeks, 186 of 242 patients (77%) received ECV. The main reason for postponing an ECV was an inadequate international normalised ratio (INR); other reasons included spontaneous sinus rhythm and switch to rate control. A total of 23 of the 147 patients (16%) managed by the research physician were postponed due to an inadequate INR at admission versus 4 out of 98 patients (4%) managed by NPs (p = 0.005) CONCLUSION: An inadequate INR is the main reason for postponing an ECV. Management of ECV by NPs is safe and leads to less postponing on admission. PMID- 22042669 TI - Is nanotechnology the key to unravel and engineer biological processes? AB - Regenerative medicine is an emerging field aiming to the development of new reparative strategies to treat degenerative diseases, injury, and trauma through developmental pathways in order to rebuild the architecture of the original injured organ and take over its functionality. Most of the processes and interactions involved in the regenerative process take place at subcellular scale. Nanotechnology provides the tools and technology not only to detect, to measure, or to image the interactions between the different biomolecules and biological entities, but also to control and guide the regenerative process. The relevance of nanotechnology for the development of regenerative medicine as well as an overview of the different tools that contribute to unravel and engineer biological systems are presented in this chapter. In addition, general data about the social impact and global investment in nanotechnology are provided. PMID- 22042670 TI - Synthesis of genetically engineered protein polymers (recombinamers) as an example of advanced self-assembled smart materials. AB - In this chapter, we describe two methods for bio-producing recombinant repetitive polypeptide polymers for use in biomedical devices. These polymers, known as elastin-like recombinamers (ELRs), are derived from the repetition of selected amino acid domains of extracellular matrix proteins with the aim of recreating their mechanical and physiological features. The proteinaceous nature of ELRs allows us to make use of the natural biosynthetic machinery of heterologous hosts to express advanced and large polymers or "recombinamers." Despite the essentially unlimited possibilities for designing recombinamers, the production of synthetic genes to encode them should allow us to overcome the difficulties surrounding bioproduction of these non-natural monotonous DNA and protein sequences. The aim of this work is to supply the biotechnologist with fine-tuning methods to biosynthesize advanced self-assembled smart materials. PMID- 22042671 TI - Design of biomolecules for nanoengineered biomaterials for regenerative medicine. AB - An important goal in the development of highly functional organic materials is to design self-assembling molecules that can reproducibly display chemical signals across length scales. Within the biomedical field, biomolecules are highly attractive candidates to serve as bioactive building blocks for the next generation of biomaterials. The peptide amphiphiles (PAs) developed by the Stupp Laboratory at Northwestern University generated a highly versatile self-assembly code to create well-defined bioactive nanofibers that have been proven to be very effective at signaling cells in vitro and in vivo. Here, we describe the basic steps necessary for synthesis and assembly of PA molecules into functional nanostructures. PMID- 22042672 TI - Stimuli responsive polymers for nanoengineering of biointerfaces. AB - There is an increasing demand on the development of "smart" switchable interfaces since controlling surface topography and chemical functionality on a nanometer scale is crucial for numerous biomedical applications. Those surfaces, which are based on stimuli responsive polymers (SRPs), are able to modify their interactions with cells, biomolecules responding to different physical (e.g., temperature) or chemical (e.g., pH) stimuli. Such behavior may partially mimic complex dynamic properties of natural systems that are regulated by many biological stimuli. This paper reviews major studies and applications of SRPs as biointerfaces in a form of thin polymeric films (gels) and surface tethered polymers (brushes). PMID- 22042673 TI - Micro/nanopatterning of proteins using a nanoimprint-based contact printing technique. AB - Micro and nanoscale protein patterning based on microcontact printing technique on large substrates have often resolution problems due to roof collapse of the poly(dimethylsiloxane) (PDMS) stamps used. Here, we describe a technique that overcomes these issues by using instead a stamp made of poly(methyl methacrylate) (PMMA), a much more rigid polymer that do not collapse even using stamps with very high aspect ratios (up to 300:1). Conformal contact between the stamp and the substrate is achieved because of the homogeneous pressure applied via the nanoimprint lithography instrument, and it has allowed us to print lines of protein 150 nm wide, at a 400 nm period. This technique, therefore, provides an excellent method for the direct printing of high-density submicrometer scale patterns, or, alternatively, micro/nanopatterns spaced at large distances. PMID- 22042675 TI - Fabrication of PEG hydrogel microwell arrays for high-throughput single stem cell culture and analysis. AB - Microwell arrays are cell culture and imaging platforms to assess cells at a single cell level and in high-throughput. They allow the spatial confinement of single cells in microfabricated cavities on a substrate and thus the continuous long-term observation of single cells and their progeny. The recent development of microwell arrays from soft, biomimetic hydrogels further increases the physiological relevance of these platforms, as it substantially enhances stem cell survival and the efficiency of self-renewal or differentiation. This protocol describes the microfabrication of such hydrogel microwell arrays, as well as the cell handling and imaging. PMID- 22042674 TI - Functionalization of surfaces with synthetic oligonucleotides. AB - There is a large interest in the use of nucleic acids covalently bound to surfaces for a variety of biomedical uses: biosensors, microarrays, drug delivery, lab-on-chip devices, and gene therapy, etc. Most of these applications require the covalent attachment of oligonucleotides via specific reactive groups on both modified oligonucleotide and/or surface. The purpose of this chapter is to provide experimental protocols for the synthesis of oligonucleotides and for the immobilization of these synthetic oligonucleotides onto surfaces such as gold and silicon oxide. PMID- 22042676 TI - Preparation of polyelectrolyte nanocomplexes containing recombinant human hepatocyte growth factor as potential oral carriers for liver regeneration. AB - The large number of cytokines and growth factors implicated in the regulation of liver regeneration has led to the possibility of using these molecules in therapy, namely, in the case of recombinant human hepatocyte growth factor (rhHGF). The importance and potential clinical usefulness of rhHGF has been extensively studied and documented, with results suggesting that this molecule could be a powerful tool toward increased success in hepatic regenerative therapy. However, the peptidic nature of this drug presents several challenges toward its effective administration and targeting. The possibility of encapsulating rhHGF in dextran sulfate/chitosan nanoparticles to allow its oral administration and direct liver-targeting is discussed in this manuscript. Details of a rapid and simple method for the preparation of such rhHGF-loaded nanocomplexes are presented. Beyond the practical aspects of the method, characterization techniques and main experimental features of obtained nanocarriers are also briefly analyzed and discussed. PMID- 22042677 TI - Electrospinning technology in tissue regeneration. AB - Electrospinning is one of the most versatile and effective tools to produce nanostructured fibers in the biomedical science fields. The nanofibrous structure with diameters from tens to hundreds of nanometers largely mimics the native extracellular matrix (ECM) of many tissues. Thus far, a range of compositions including polymers and ceramics and their composites/hybrids have been successfully applied for generating electrospun nanofibers. Different processing tools in electrospinning set-ups and assemblies are currently developed to tune the morphology and properties of nanofibers. Herein, we demonstrate the electrospinning process and the electrospun biomaterials for specific use in tissue regeneration with some examples, involving different material combinations and fiber morphologies. PMID- 22042678 TI - Protein adsorption characterization. AB - Protein adsorption from (aqueous) solutions onto a (solid) surface is a common process that takes place at biological interfaces. This phenomenon, that spontaneously occurs, changes the properties of the surface and can induce structural modifications on proteins. Proteins in solution can be easily identified/quantified using classical biochemical methods. However, adsorbed proteins are more difficult to assess since they are always associated with a substrate. The selection of the analytical method depends on the type of substrate used, the amount of adsorbed protein, the type of solution (single protein solution vs. complex biological media), and the type of information that is demanded (quantification of the adsorbed protein, adsorption kinetics, conformation, and orientation of the adsorbed protein). Until now, none of the techniques available are capable by its own to characterize all the protein adsorption process. Therefore, a multitechnique analysis is required. During this chapter, the methodologies to measure human serum albumin to poly(ethylene terephthalate) using the three different techniques, radiolabeling, ellipsometry, and quartz crystal microbalance with dissipation - QCM-D, are described in detail. The specific preparation of polymeric surfaces to be used with each technique is also presented. PMID- 22042679 TI - Measuring wettability of biosurfaces at the microscale. AB - Determining the contact angle of a liquid on a solid surface is a simple method to assess the surface wettability. The most common method to measure the contact angle of a liquid consists of capturing the profile of a sessile drop of a few microliters on the surface using an optical system. Currently, this is a widely used technique to analyze wettability both in researched materials and in products of multiple technological fields. However, the drop dispensed by a traditional macroscopic contact angle meter is too big to assess the wettability properties of individual topographical features and/or chemical patterns at the micro/nanoscale. Recently, contact angle meters that can discharge drops that are microscopic, with volumes in the range of 1 * 10(-3) to 10(-5) MUL have been developed. The novel microscopic contact angle meter uses a pneumatic injection system to discharge the drop of the liquid through a capillary of a few micrometers of internal diameter and a high-resolution ultrafast digital camera. We have tested different biosurfaces - microimprinted polymers for biosensors, calcium-phosphate cements with different topographical microfeatures, orthodontic wires - and assessed the potential applicability in the field in comparison with the conventional macroscopic contact angle meters. This protocol describes the basic tasks needed to test wettability on biosurfaces with a microscopic contact angle meter. The focus of the protocol is on the challenging methodological steps and those that differentiate the use of this equipment to the use of a traditional macroscopic contact angle meter. PMID- 22042680 TI - AFM to study bio/nonbio interactions. AB - This chapter describes a versatile approach to immobilize proteins and other biomolecules on reactive self-assembled monolayers on gold as a means to study interactions (forces) between these biomolecules and nonbiological entities. Biomolecules are either immobilized on the surface of flat substrates or on the surface of gold-coated atomic force microscopy (AFM) probe tips. In addition to the immobilization protocols, the actual AFM experiments in liquid and the quantitative analysis of adhesive forces receive attention. With these procedures and tools at hand, a wide variety of problems in the area of bio/nonbio interactions can be addressed experimentally. PMID- 22042681 TI - Evaluation of cytocompatibility and cell response to boron nitride nanotubes. AB - While in the last years applications of carbon nanotubes in the field of biotechnology have been largely proposed, so far biomedical applications of boron nitride nanotubes (BNNTs) are still totally unexplored. BNNTs show very interesting physical properties that might be exploited in the nanomedicine field. To fill up the lack of biocompatibility studies on BNNTs, our group has recently begun a rational investigation on interactions between BNNTs and different cell lines. This chapter reports on preliminary cytocompatibility studies carried out on human neuroblastoma (SH-SY5Y) and on mouse myoblast (C2C12) cell lines as model of neural and skeletal muscle cells, respectively, highlighting the methods that allowed us to evaluate the main parameters of interests for cytocompatibility, such as cell viability, metabolism, apoptosis, and differentiation. PMID- 22042682 TI - Nanobiosensors for in vitro and in vivo analysis of biomolecules. AB - This chapter presents as a proof of concept the development of a nanosensor based on the localized surface plasmon resonance for the analysis of biomolecules. The method presented take advantage of the plasmon generated in the surrounding of gold nanoparticles (i.e., 100 nm) for the specific interaction between antigen and antibody. The procedure for the optimization of an assay for the determination of biomolecules consisted mainly of four steps. First, the immobilization of gold nanoparticles over the glass surface using the appropriate ratio, concentration and time-contact of amino-sylilating agent, and nonreactive sylilating agent. Next, the suitable concentration of coating antigen in order to obtain the maximum signal LSPR. Following this step, the interaction between antigen and antibody (specific antibody) is evaluated by measuring the signal LSPR. Finally, a calibration curve was obtained for the detection of a small organic molecule such as stanozolol using this nanobiosensor. As a proof of concept, the use of a model is performed that in this case is for the detection of an anabolic androgenic steroid, such as stanozolol which is banned for the European Commission (EC) as a growth promoter and for the World Anti-Doping Agency (WADA) as a doping agent. The nanosensor developed demonstrates its feasibility for screening purposes due to the limit of detection achieved (0.7 MUg/L) is under the MRPL required for both organizations (10 MUg/L). A protocol such as that presented here may be generally applied for the analysis of other pollutant such as pesticides or antibiotics, or for biomedical applications for the analysis of biomarkers using the LSPR principle using gold nanoparticles (i.e., 30-120 nm). PMID- 22042683 TI - Novel strategies to engineering biological tissue in vitro. AB - Tissue engineering creates biological tissues that aim to improve the function of diseased or damaged tissues. In this chapter, we examine the promise and shortcomings of "top-down" and "bottom-up" approaches for creating engineered biological tissues. In top-down approaches, the cells are expected to populate the scaffold and create the appropriate extracellular matrix and microarchitecture often with the aid of a bioreactor that furnish the set of stimuli required for an optimal cellular viability. Specifically, we survey the role of cell material interaction on oxygen metabolism in three-dimensional (3D) in vitro cultures as well as the time and space evolution of the transport and biophysical properties during the development of de novo synthesized tissue engineered constructs. We show how to monitor and control the evolution of these parameters that is of crucial importance to process biohybrid constructs in vitro as well as to elaborate reliable mathematical model to forecast tissue growth under specific culture conditions. Furthermore, novel strategies such as bottom up approaches to build tissue constructs in vitro are examined. In this fashion, tissue building blocks with specific microarchitectural features are used as modular units to engineer biological tissues from the bottom up. In particular, the attention will be focused on the use of cell seeded microbeads as functional building blocks to realize 3D complex tissue. Finally, a challenge will be the potential integration of bottom-up techniques with more traditional top-down approaches to create more complex tissues than are currently achievable using either technique alone by optimizing the advantages of each technique. PMID- 22042684 TI - Enabling biomedical research with designer quantum dots. AB - Quantum Dots (QDs) are a new class of semiconductor nanoparticulate luminophores, which are actively researched for novel applications in biology and nanomedicine. In this review, the recent progress in the design and applications of QD labels for in vitro and in vivo imaging of cells is presented. Surface chemical engineering of hydrophobic QDs is required to render them water soluble and biocompatible. Further surface modification and attachment of bioactive molecules to the surface of QDs, such as peptides, aptamers, or antibodies are intensively explored for targeted imaging of living cells, and disease states in animals. Specially designed surface coatings can drastically decrease nonspecific interactions between QDs and cells, minimize degradation of QDs under in vivo physiological conditions, reduce the cytotoxicity of QDs, and prolong circulation lifetimes in animals. New generations of QD probes are also promising for imaging cellular processes at the single-molecule level. Ultimately, QDs as components of complex therapeutic nanosystems are poised to contribute significantly to the field of personalized medicine. PMID- 22042685 TI - The role of nanophotonics in regenerative medicine. AB - Cells respond to biochemical and mechanical stimuli through a series of steps that begin at the molecular, nanometre level, and translate finally in global cell response. Defects in biochemical- and/or mechanical-sensing, transduction or cellular response are the cause of multiple diseases, including cancer and immune disorders among others. Within the booming field of regenerative medicine, there is an increasing need for developing and applying nanotechnology tools to bring understanding on the cellular machinery and molecular interactions at the nanoscale. Nanotechnology, nanophotonics and in particular, high-resolution-based fluorescence approaches are already delivering crucial information on the way that cells respond to their environment and how they organize their receptors to perform specialized functions. This chapter focuses on emerging super-resolution optical techniques, summarizing their principles, technical implementation, and reviewing some of the achievements reached so far. PMID- 22042686 TI - Molecular dynamics methods for modeling complex interactions in biomaterials. AB - The molecular dynamics method is a powerful computer simulation technique which provides access to the detailed time evolution (trajectory) of a system in specified conditions, such as a particular temperature or pressure. The full trajectory of the system can be analyzed using statistical mechanics tools to obtain thermodynamical quantities and dynamical properties; the mechanism of chemical reactions and other time-dependent processes, such as diffusion, can also be revealed in high detail. When applied to model extended and complex system such as biomaterials, MD simulations represent an invaluable tool to discover structure-activity relationships and rationalize biomedical applications. PMID- 22042687 TI - Regenerative nanomedicine: ethical, legal, and social issues. AB - Advances in regenerative nanomedicine raise a host of ethical, legal, and social questions that healthcare providers and scientists will need to consider. These questions and concerns include definitions, appropriate applications, dual use, potential risks, regulations, and access. In this chapter, we provide an overview of the questions and concerns and recommend proactive consideration and solutions. PMID- 22042688 TI - Paleodiet of extinct platyrrhines with emphasis on the Caribbean forms: three dimensional geometric morphometrics of mandibular second molars. AB - A three-dimensional geometric morphometric approach was employed to examine shape variation in laser-scan generated models of lower second molars and its relationship to diet in a sample of 9 extant and 16 extinct platyrrhine genera. Principal component analysis of twenty-three x,y,z landmarks describing the occlusal table and sidewalls showed that dental relief was the main contributing factor to variation along the first axis. Discriminant function analysis (DFA) of PC 1 scores and centroid size accurately classified extant platyrrhines according to dietary preference; however, without centroid size, the DFA was less successful. Within this framework, most of the fossil platyrrhines, including specimens from Patagonia, Colombia, Brazil, and the Caribbean, were predicted to have had a frugivorous diet, but several taxa were classified as having a frugivorous/insectivorous diet, the middle Miocene Neosaimiri, Patasola, and Laventiana, all from La Venta. Alouattins, including the La Ventan Stirtonia and the Cuban Paralouatta, showed variable classification as either frugivores or folivore/frugivores. Xenothrix, from Jamaica, was classified either as a frugivore or frugivore/omnivore. Dietary profiles across different extinct platyrrhine communities are compared and discussed in a paleoecological context. PMID- 22042689 TI - MATCH: an atom-typing toolset for molecular mechanics force fields. AB - We introduce a toolset of program libraries collectively titled multipurpose atom typer for CHARMM (MATCH) for the automated assignment of atom types and force field parameters for molecular mechanics simulation of organic molecules. The toolset includes utilities for the conversion of multiple chemical structure file formats into a molecular graph. A general chemical pattern-matching engine using this graph has been implemented whereby assignment of molecular mechanics atom types, charges, and force field parameters are achieved by comparison against a customizable list of chemical fragments. While initially designed to complement the CHARMM simulation package and force fields by generating the necessary input topology and atom-type data files, MATCH can be expanded to any force field and program, and has core functionality that makes it extendable to other applications such as fragment-based property prediction. In this work, we demonstrate the accurate construction of atomic parameters of molecules within each force field included in CHARMM36 through exhaustive cross validation studies illustrating that bond charge increment rules derived from one force field can be transferred to another. In addition, using leave-one-out substitution it is shown that it is also possible to substitute missing intra and intermolecular parameters with ones included in a force field to complete the parameterization of novel molecules. Finally, to demonstrate the robustness of MATCH and the coverage of chemical space offered by the recent CHARMM general force field (Vanommeslaeghe, et al., J Comput Chem 2010, 31, 671), one million molecules from the PubChem database of small molecules are typed, parameterized, and minimized. PMID- 22042690 TI - Correlation between BIS and GCS in patients suffering from head injury. AB - OBJECTIVES AND BACKGROUND: Glasgow coma scale (GCS) is considered an important parameter to predict the clinical outcome in head injury; however, in some cases such as the use of sedative drugs the estimate of GCS would not be precise. Bispectral index (BIS) is an electrophysiological parameter to determine the clinical state of anesthesia. The aim of the present study is to evaluate correlation between GCS and BIS in patients suffering from head injury and to see if we can use BIS values as a prognostic factor in head trauma. METHODS: In this analytic study 61 consecutive patients with traumatic head injury admitted to the intensive care unit from January till June 2010 were examined. In each case the GCS and BIS values were measured and compared regarding different degrees of head injuries. RESULTS: Mean BIS in mild injury group was 96.20 +/- 3.27 and in moderate injury group was 45.57 +/- 1.28 and in severe injury group was 31.37 +/- 2.08. There was a significant correlation between GCS and mean BIS (r = 0.88; P < 0.05). Mean BIS values were significantly different between mild, moderate and severe head injuries (96.2 +/- 3.2, 45.5 +/- 1.2, and 31.3 +/- 2.08, respectively; P < 0.05). CONCLUSION: We found significant correlation between GCS and BIS in patients with traumatic head injury, so BIS can be used in addition to GCS for prediction of outcome in these patients specially in patients who are sedated or are intubated or in other case in whom GCS values cannot be determined accurately. PMID- 22042691 TI - Biocompatibility and biodegradation of polycaprolactone-sebacic acid blended gels. AB - Tissue engineering aims at creating biological body parts as an alternative for transplanting tissues and organs. A current new approach for such materials consists in injectable biodegradable polymers. Their major advantages are the ability to fill-in defects, easy incorporation of therapeutic agents or cells, and the possibility of minimal invasive surgical procedures. Polycaprolactone (PCL) is a promising biodegradable and elastic biomaterial, with the drawback of low-degradation kinetics in vivo. In this work a biodegradable injectable gel of PCL blended with sebacic acid (SA) was prepared, to improve the degradation rate of the biomaterial. SA is known for its high degradation rate, although in high concentrations it could originate a pH decrease and thus disturb the biocompatibility of PCL. Degradation tests on phosphate buffered saline were carried out using 5% of SA on the blend and the biomaterial stability was evaluated after degradation using differential scanning calorimetry, dynamical mechanical analysis, and scanning electronic microscopy. After degradation the elastic properties of the blend decreased and the material became more crystalline and stiffer, although at a lower extent when compared with pure PCL. The blend also degraded faster with a loss of the crystalline phase on the beginning (30 days), although its thermal and mechanical properties remained comparable with those of the pure material, thus showing that it achieved the intended objectives. After cell assays the PCL-SA gel was shown to be cytocompatible and capable of maintaining high cell viability (over 90%). PMID- 22042692 TI - Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study. AB - To clarify which is preferable, a related donor with an HLA-1 Ag mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host (GVH) direction (RD/1AG-MM GVH) or an HLA 8/8-allele (HLA-A, HLA-B, HLA-C, and HLA-DRB1)-matched unrelated donor (8/8-MUD), we evaluated 779 patients with acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome who received a T cell-replete graft from an RD/1AG-MM-GVH or 8/8-MUD. The use of an RD/1AG-MM-GVH donor was significantly associated with a higher overall mortality rate than the use of an 8/8-MUD in a multivariate analysis (hazard ratio, 1.49; P < .001), and this impact was statistically significant only in patients with standard-risk diseases (P = .001). Among patients with standard-risk diseases who received transplantation from an RD/1AG-MM-GVH donor, the presence of an HLA-B Ag mismatch was significantly associated with a lower overall survival rate than an HLA-DR Ag mismatch because of an increased risk of treatment-related mortality. The HLA-C Ag mismatch or multiple allelic mismatches were frequently observed in the HLA-B Ag-mismatched group, and were possibly associated with the poor outcome. In conclusion, an 8/8-MUD should be prioritized over an RD/1AG-MM-GVH donor during donor selection. In particular, an HLA-B Ag mismatch in the GVH direction has an adverse effect on overall survival and treatment-related mortality in patients with standard-risk diseases. PMID- 22042693 TI - B-cell replication history and somatic hypermutation status identify distinct pathophysiologic backgrounds in common variable immunodeficiency. AB - Common variable immunodeficiency disorder (CVID) is the most prevalent form of primary idiopathic hypogammaglobulinemia. Identification of genetic defects in CVID is hampered by clinical and immunologic heterogeneity. By flow cytometric immunophenotyping and cell sorting of peripheral B-cell subsets of 37 CVID patients, we studied the B-cell compartment at the B-cell subset level using the kappa-deleting recombination excision circle assay to determine the replication history and the Igkappa-restriction enzyme hot-spot mutation assay to assess the somatic hypermutation status. Using this approach, 5 B-cell patterns were identified, which delineated groups with unique replication and somatic hypermutation characteristics. Each B-cell pattern reflected an immunologically homogenous patient group for which we proposed a different pathophysiology: (1) a B-cell production defect (n = 8, 18%), (2) an early peripheral B-cell maturation or survival defect (n = 4, 11%), (3) a B-cell activation and proliferation defect (n = 12, 32%), (4) a germinal center defect (n = 7, 19%), and (5) a postgerminal center defect (n = 6, 16%). The results of the present study provide for the first time insight into the underlying pathophysiologic background in 5 immunologically homogenous groups of CVID patients. Moreover, this study forms the basis for larger cohort studies with the defined homogenous patient groups and will facilitate the identification of underlying genetic defects in CVID. PMID- 22042694 TI - FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death. AB - Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a short median survival despite multimodal therapy. FTY720, an immunosuppressive drug approved for the treatment of multiple sclerosis, promotes MCL cell death concurrent with down-modulation of phospho-Akt and cyclin D1 and subsequent cell-cycle arrest. However, the mechanism of FTY720-mediated MCL cell death remains to be fully clarified. In the present study, we show features of autophagy blockage by FTY720 treatment, including accumulation of autolysosomes and increased LC3-II and p62 levels. We also show that FTY720-induced cell death is mediated by lysosomal membrane permeabilization with subsequent translocation of lysosomal hydrolases to the cytosol. FTY720-mediated disruption of the autophagic-lysosomal pathway led to increased levels of CD74, a potential therapeutic target in MCL that is degraded in the lysosomal compartment. This finding provided rationale for examining combination therapy with FTY720 and milatuzumab, an anti-CD74 mAb. Treatment of MCL cell lines and primary tumor cells with FTY720 and milatuzumab resulted in statistically significant enhanced cell death, which was synergistic in blastic variant MCL cell lines. Significant in vivo therapeutic activity of combination treatment was also demonstrated in a preclinical, in vivo model of MCL. These findings support clinical evaluation of this combination in patients with MCL. PMID- 22042695 TI - Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight. AB - Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model. The potential to reduce blood sampling was also explored. A model was built for FVIII PK from 236 infusions of recombinant FVIII in 152 patients (1-65 years of age) with severe hemophilia A. The PK of FVIII over the entire age range was well described by a 2-compartment model and a previously reported problem, resulting from differences in blood sampling, to compare findings from children and adults was practically abolished. The decline in FVIII clearance and increase in half life with age could be described as continuous functions. Retrospective reduction of blood sampling from 11 to 5 samples made no important difference to the estimates of PK parameters. The obtained findings can be used as a basis for PK based dose tailoring of FVIII in clinical practice, in all age groups, with minimal blood sampling. PMID- 22042696 TI - Critical role for perforin and Fas-dependent killing of dendritic cells in the control of inflammation. AB - After stimulation of antigen-specific T cells, dendritic cell (DCs) are susceptible to killing by these activated T cells that involve perforin and Fas dependent mechanisms. Fas-dependent DC apoptosis has been shown to limit DC accumulation and prevent the development of autoimmunity. However, a role for perforin in the maintenance of DC homeostasis for immune regulation remains to be determined. Here we show that perforin deficiency in mice, together with the deletion of Fas in DCs (perforin(-/-)DC-Fas(-/-)), led to DC accumulation, uncontrolled T-cell activation, and IFN-gamma production by CD8+ T cells, resulting in the development of lethal hemophagocytic lymphohistiocytosis. Consistently, adoptive transfer of Fas(-/-) DCs induced over-activation and IFN gamma production in perforin(-/-) CD8+ T cells. Neutralization of IFN-gamma prevented the spreading of inflammatory responses to different cell types and protected the survival of perforin(-/-)DC-Fas(-/-) mice. Our data suggest that perforin and Fas synergize in the maintenance of DC homeostasis to limit T cell activation, and prevent the initiation of an inflammatory cascade. PMID- 22042697 TI - Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease. AB - Protracted inhibition of osteoblast (OB) differentiation characterizes multiple myeloma (MM) bone disease and persists even when patients are in long-term remission. However, the underlying pathophysiology for this prolonged OB suppression is unknown. Therefore, we developed a mouse MM model in which the bone marrow stromal cells (BMSCs) remained unresponsive to OB differentiation signals after removal of MM cells. We found that BMSCs from both MM-bearing mice and MM patients had increased levels of the transcriptional repressor Gfi1 compared with controls and that Gfi1 was a novel transcriptional repressor of the critical OB transcription factor Runx2. Trichostatin-A blocked the effects of Gfi1, suggesting that it induces epigenetic changes in the Runx2 promoter. MM BMSC cell-cell contact was not required for MM cells to increase Gfi1 and repress Runx2 levels in MC-4 before OBs or naive primary BMSCs, and Gfi1 induction was blocked by anti-TNF-alpha and anti-IL-7 antibodies. Importantly, BMSCs isolated from Gfi1(-/-) mice were significantly resistant to MM-induced OB suppression. Strikingly, siRNA knockdown of Gfi1 in BMSCs from MM patients significantly restored expression of Runx2 and OB differentiation markers. Thus, Gfi1 may have an important role in prolonged MM-induced OB suppression and provide a new therapeutic target for MM bone disease. PMID- 22042698 TI - Dual functions of cell-autonomous and non-cell-autonomous ADAM10 activity in granulopoiesis. AB - Previous studies have revealed various extrinsic stimuli and factors involved in the regulation of hematopoiesis. Among these, Notch-mediated signaling has been suggested to be critically involved in this process. Herein, we show that conditional inactivation of ADAM10, a membrane-bound protease with a crucial role in Notch signaling (S2 cleavage), results in myeloproliferative disorder (MPD) highlighted by severe splenomegaly and increased populations of myeloid cells and hematopoietic stem cells. Reciprocal transfer of bone marrow cells between wild type and ADAM10 mutant mice revealed that ADAM10 activity in both hematopoietic and nonhematopoietic cells is involved in the development of MPD. Notably, we found that MPD caused by lack of ADAM10 in nonhematopoietic cells was mediated by G-CSF, whereas MPD caused by ADAM10-deficient hematopoietic cells was not. Taken together, the present findings reveal previously undescribed nonredundant roles of cell-autonomous and non-cell-autonomous ADAM10 activity in the maintenance of hematopoiesis. PMID- 22042699 TI - miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. AB - Many transformed lymphoma cells show immune-phenotypes resembling the corresponding normal lymphocytes; thus, they provide a guide for proper diagnosis and present promising routes to improve their pathophysiologic understanding and to identify novel therapeutic targets. However, the underlying molecular mechanism(s) of these aberrant immune-phenotypes is largely unknown. Here, we report that microRNA-135b (miR-135b) mediates nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-driven oncogenicity and empowers IL-17-producing immunophenotype in anaplastic large cell lymphoma (ALCL). NPM-ALK oncogene strongly promoted the expression of miR-135b and its host gene LEMD1 through activation of signal transducer and activator of transcription (STAT) 3. In turn, elevated miR-135b targeted FOXO1 in ALCL cells. miR-135b introduction also decreased chemosensitivity in Jurkat cells, suggesting its contribution to oncogenic activities of NPM-ALK. Interestingly, miR-135b suppressed T-helper (Th) 2 master regulators STAT6 and GATA3, and miR-135b blockade attenuated IL-17 production and paracrine inflammatory response by ALCL cells, indicating that miR-135b-mediated Th2 suppression may lead to the skewing to ALCL immunophenotype overlapping with Th17 cells. Furthermore, antisense-based miR-135b inhibition reduced tumor angiogenesis and growth in vivo, demonstrating significance of this "Th17 mimic" pathway as a therapeutic target. These results collectively illuminated unique contribution of oncogenic kinase-linked microRNA to tumorigenesis through modulation of tumor immune-phenotype and microenvironment. PMID- 22042700 TI - Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1alpha levels in patients with MGUS. AB - Recent population-based studies demonstrate an increased fracture risk with monoclonal gammopathy of undetermined significance (MGUS). The etiology of this increased risk remains unclear, however, because areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry cannot assess bone microstructural properties critical to determining bone quality and strength. To better define the skeletal effects of MGUS, we performed aBMD and high-resolution peripheral quantitative computed tomography volumetric bone mineral density (vBMD) measurements in 50 MGUS patients (20 females, 30 males; mean +/- SEM age, 70.5 +/- 1.4 years) and 100 matched control subjects. Relative to controls, MGUS patients had decreased aBMD at the femoral neck (P = .05) and total femur (P < .05) but no differences at other sites. In contrast, high-resolution peripheral quantitative computed tomography showed markedly diminished cortical thickness (P < .05) and increased endocortical area (P < .01). Average vBMD (P < .01), cortical vBMD (P < .001), and trabecular thickness (P < .01) were all significantly decreased in MGUS patients, suggestive of impaired bone formation. Serum levels of the Wnt pathway inhibitor Dickkopf-related protein 1 (P < .001) and osteoclast-activating factor MIP-1alpha (P < .05) also were significantly elevated in MGUS patients. Our data provide the first evidence of altered bone microstructure in MGUS and suggest that cytokines elevated in osteolytic myeloma also may be associated with bone loss in MGUS. PMID- 22042701 TI - Dependency on the polycomb gene Ezh2 distinguishes fetal from adult hematopoietic stem cells. AB - Polycomb-group (PcG) proteins are essential regulators of hematopoietic stem cells (HSCs). In contrast to Bmi1, a component of Polycomb repressive complex 1 (PRC1), the role of PRC2 and its components in hematopoiesis remains elusive. Here we show that Ezh2, a core component of PRC2, is essential for fetal, but not adult, HSCs. Ezh2-deficient embryos died of anemia because of insufficient expansion of HSCs/progenitor cells and defective erythropoiesis in fetal liver. Deletion of Ezh2 in adult BM, however, did not significantly compromise hematopoiesis, except for lymphopoiesis. Of note, Ezh2-deficient fetal liver cells showed a drastic reduction in trimethylation of histone H3 at lysine 27 (H3K27me3) accompanied by derepression of a large cohort of genes, whereas on homing to BM, they acquired a high level of H3K27me3 and long-term repopulating capacity. Quantitative RT-PCR revealed that Ezh1, the gene encoding a backup enzyme, is highly expressed in HSCs/progenitor cells in BM compared with those in fetal liver, whereas Ezh2 is ubiquitously expressed. These findings suggest that Ezh1 complements Ezh2 in the BM, but not in the fetal liver, and reveal that the reinforcement of PcG-mediated gene silencing occurs during the transition from proliferative fetal HSCs to quiescent adult HSCs. PMID- 22042702 TI - Best evidence in critical care medicine: The role of neuromuscular blocking drugs in early severe acute respiratory distress syndrome. AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is defined as severe hypoxemic respiratory failure resulting from diffuse lung injury and secondary to direct and indirect insults. Despite advances, mortality remains as high as 40 60%. Neuromuscular blocking agents (NMBAs) are used to facilitate mechanical ventilation in patients with ARDS and have been shown to improve arterial partial pressure of oxygen. However, the association between NMBAs and mortality is unclear. Furthermore, morbidity concerns exist, particularly regarding a putative role in intensive care unit (ICU)-acquired weakness. OBJECTIVE: The purpose of this study was to compare survival in adult patients with early ARDS who were randomized to receive either a 48-hr infusion of the NMBA, cisatracurium, or a placebo. DESIGN AND SETTING: This study was a multicentre double-blinded randomized controlled trial involving 20 ICUs in France from March 2006 to March 2008. PATIENTS: Eligible patients were > 18 yr with an intubated trachea and ventilated lungs for acute hypoxemic respiratory failure. Their PaO(2)/F(i)O(2) ratio was < 150 at a tidal volume of 6-8 mL.kg(-1) ideal body weight and a positive end-expiratory pressure (PEEP) >= 5 cm H(2)O for < 48 hr. Additional inclusion criteria were radiographic evidence of bilateral pulmonary infiltrates and the absence of left atrial hypertension. Exclusion criteria included patients already receiving NMBA at enrolment; those who had increased intracranial pressure, severe chronic respiratory disease, or severe chronic liver disease; those who had received a bone marrow transplant or had chemotherapy-induced neutropenia; those who had a pneumothorax; and those who were expected to require mechanical ventilation for < 48 hr or were enrolled in another trial within 30 days. INTERVENTION: Three hundred twenty-six patients were screened, and 340 of these underwent randomization in blocks of four and received either a 48-hr infusion of cisatracurium (15 mg bolus followed by 37.5 mg.hr(-1)) or a volume equivalent placebo. One hundred and seventy-eight patients received a cisatracurium infusion, and one patient withdrew leaving 177 patients included in the analysis. One hundred and sixty-two patients received the placebo infusion. Prior to either infusion, patients were sedated to a Ramsay sedation score of 6. Patients' lungs were ventilated by a volume assist-controlled mode according to the ARDS Clinical Network Mechanical Ventilation Protocol (http://www.ardsnet.org/) with the goal SpO(2) of 88-95% (or PaO(2) 55-80 mmHg) and goal plateau pressure <= 35 cm H(2)O. Open-label boluses of cisatracurium 20 mg (maximum of two per 24-hr period) were allowed if plateau pressures remained > 32 cm H(2)O despite increased sedation and despite decreased PEEP and decreased tidal volumes. Monitoring of paralysis via peripheral nerve stimulation was not permitted. MEASUREMENTS: The primary outcome was death before hospital discharge and within 90 days of study enrolment. It was determined a priori that this would be adjusted for imbalance in key risk factors at baseline, as derived from Cox regression. Secondary outcomes included 28-day mortality, number of ventilator free days, number of days outside of ICU, number of days without organ system failure, rate of barotrauma, and rate of ICU-acquired paresis (as defined by a Medical Research Council [MRC] score < 48) on day 28 and at ICU discharge. MAIN RESULTS: With regard to the primary outcome, crude 90-day mortality was 31.6% in the cisatracurium group vs 40.7% in the placebo group. This outcome did not reach statistical significance (P = 0.08). However, post hoc analysis found a reduction in 90-day mortality in the cisatracurium group compared with placebo (95% confidence interval 0.48 to 0.98; P = 0.04). Results suggest that the reduction in 90-day mortality in the cisatracurium group was confined to those patients with a PaO(2)/F(i)O(2) ratio < 120. Additionally, 28-day mortality was significantly lower in the cisatracurium group (absolute difference -9.6%; P = 0.05). The cisatracurium group also had significantly more ventilator-free days, more days outside of the ICU, and more days free of organ-failure. Similarly, pneumothorax developed more often and earlier in the placebo group than in the cisatracurium group. The rate of ICU-acquired weakness at day 28 or at ICU discharge did not differ significantly between the two groups. CONCLUSIONS: Treatment in early severe ARDS with the NMBA, cisatracurium, for 48 hr was associated with lower adjusted 90-day mortality. It was also associated with decreased morbidity, which included increased ventilator-free days, increased ICU free days, and increased organ failure-free days. These benefits occurred without increasing the incidence of ICU-acquired weakness. PMID- 22042703 TI - Effect of dexamethasone on postoperative morbidity after dental rehabilitation in children. AB - PURPOSE: Dexamethasone reduces postoperative morbidity after adenotonsillectomy, strabismus surgery, and third molar extraction. Our hypothesis was that dexamethasone would reduce pain and other morbidity in children undergoing dental surgery for up to 24 hr postoperatively. METHODS: A triple-blinded, randomized, controlled trial was carried out on 200 children undergoing prolonged dental rehabilitation under general anesthesia. Subjects were randomized into two groups: group D, given dexamethasone 0.3 mg.kg(-1); group S, given normal saline. The primary outcome measure was pain over 24 hr as evaluated by a parental 0-10 numerical rating scale (NRS). Key secondary outcomes included oral intake on a four-point scale at 24 hr and the overall incidence of postoperative vomiting (POV). Analysis for the primary outcome consisted of comparison of means in the NRS with the Wilcoxon rank sum test and for occurrence of POV with Fisher's test. RESULTS: After eliminating 22 subjects for protocol violations and withdrawals, 178 subjects were analyzed. There was no significant difference in pain scores (NRS) at 24 hr or the worst NRS experienced over the preceding 24 hr. There was no difference in the quality of oral intake between the groups. There was a significant difference in the percentage of patients who vomited during the first 24 hr: eight of 91 in group S and one of 87 in group D. Therefore, 7.74% more vomited in group S (P = 0.045), with a 95% confidence interval of 0.32 to15.16 for the difference in percentages. CONCLUSIONS: Dexamethasone, 0.3 mg.kg(-1), did not reduce pain over 24 hr in healthy children undergoing dental rehabilitation under general anesthesia. The quality of oral intake was also unaffected by dexamethasone at 24 hr. Dexamethasone did produce a significant reduction in postdischarge vomiting, beyond the incidence found with ondansetron alone. PMID- 22042704 TI - Persistent left superior vena cava: implications during central venous cannulation. PMID- 22042707 TI - Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease. AB - Detectable cognitive decline occurs in patients with Alzheimer's disease (AD) well before the clinical diagnosis can be made with any certainty. Studies examining this preclinical period identify decline in episodic memory as the earliest manifestation of the disease (i.e., a condition of amnestic Mild Cognitive Impairment). The episodic memory impairment is characterized by deficits in a number of processes including delayed recall, the recollective aspect of recognition memory, associative memory necessary for "binding" representations of two or more stimuli, pattern separation necessary to distinguish between two similar memory representations, prospective memory required to remember a delayed intention to act at a certain time in the future, and autobiographical memory for specific episodes that occurred in one's past. A growing body of evidence suggests that cognitive changes in preclinical AD may be more global in nature. Deterioration of semantic knowledge is evident on demanding naming and category fluency tasks, and "executive" dysfunction is apparent on tasks that require concurrent mental manipulation of information (e.g., working memory) or cue-directed behavior (e.g., set-shifting). Asymmetric cognitive test performance may also be apparent prior to significant decline in cognitive ability. The pattern and progression of these neuropsychological changes fit well with the proposed distribution and spread of AD pathology and serve as important cognitive markers of early disease. PMID- 22042705 TI - Glidescope(r) video-laryngoscopy versus direct laryngoscopy for endotracheal intubation: a systematic review and meta-analysis. AB - INTRODUCTION: The Glidescope((r)) video-laryngoscopy appears to provide better glottic visualization than direct laryngoscopy. However, it remains unclear if it translates into increased success with intubation. METHODS: We systematically searched electronic databases, conference abstracts, and article references. We included trials in humans comparing Glidescope((r)) video-laryngoscopy to direct laryngoscopy regarding the glottic view, successful first-attempt intubation, and time to intubation. We generated pooled risk ratios or weighted mean differences across studies. Meta-regression was used to explore heterogeneity based on operator expertise and intubation difficulty. RESULTS: We included 17 trials with a total of 1,998 patients. The pooled relative risk (RR) of grade 1 laryngoscopy (vs >= grade 2) for the Glidescope((r)) was 2.0 [95% confidence interval (CI) 1.5 to 2.5]. Significant heterogeneity was partially explained by intubation difficulty using meta-regression analysis (P = 0.003). The pooled RR for nondifficult intubations of grade 1 laryngoscopy (vs >= grade 2) was 1.5 (95% CI 1.2 to 1.9), and for difficult intubations it was 3.5 (95% CI 2.3 to 5.5). There was no difference between the Glidescope((r)) and the direct laryngoscope regarding successful first-attempt intubation or time to intubation, although there was significant heterogeneity in both of these outcomes. In the two studies examining nonexperts, successful first-attempt intubation (RR 1.8, 95% CI 1.4 to 2.4) and time to intubation (weighted mean difference -43 sec, 95% CI -72 to -14 sec) were improved using the Glidescope((r)). These benefits were not seen with experts. CONCLUSION: Compared to direct laryngoscopy, Glidescope((r)) video laryngoscopy is associated with improved glottic visualization, particularly in patients with potential or simulated difficult airways. PMID- 22042708 TI - Academic integrity in a mandatory physics lab: the influence of post-graduate aspirations and grade point averages. AB - Research on academic cheating by high school students and undergraduates suggests that many students will do whatever it takes, including violating ethical classroom standards, to not be left behind or to race to the top. This behavior may be exacerbated among pre-med and pre-health professional school students enrolled in laboratory classes because of the typical disconnect between these students, their instructors and the perceived legitimacy of the laboratory work. There is little research, however, that has investigated the relationship between high aspirations and academic conduct. This study fills this research gap by investigating the beliefs, perceptions and self-reported academic conduct of highly aspirational students and their peers in mandatory physics labs. The findings suggest that physics laboratory classes may face particular challenges with highly aspirational students and cheating, but the paper offers practical solutions for addressing them. PMID- 22042709 TI - Life-history correlates of enamel microstructure in cebidae (Platyrrhini, Primates). AB - Previous studies have examined tooth eruption as it relates intrinsically to body mass, brain mass, and other life history variables, and extrinsically to ecological factors (e.g., age at foraging independence, environmental risk aversion, and maternal investment). Different models have been explored wherein each of these variables impacts ontogeny. However, anthropoid and strepsirhine primates exhibit interesting differences in the relationships of these ecological and life history variables with tooth eruption. Moreover, interactions between ecological variables and dental tissue growth have only been explored in the lemurs. This study examines dental microstructure of the New World monkey family, Cebidae, to provide further insight into forces influencing the evolution of primate dental ontogeny. The Cebidae were chosen because they are a diverse group which is distinct in ecology and phylogeny from the better known catarrhines of the Old World. Using phylogenetic generalized least squares analyses (PGLS), we test whether brain mass, body mass, or the three above-mentioned ecological variables have stronger correlations with enamel growth. Results show that ecological factors have stronger relationships with cebid dental growth rates than brain or body mass. Foraging independence has the most impact on overall enamel growth as it has the strongest correlation with enamel extension rates. However, another estimate of enamel growth, rate of secretion, has the highest correlation with maternal investment. Our results suggest that an overarching ecological model encompassing the three current ecological hypotheses is needed to further understand the evolution of dental ontogeny within primates. PMID- 22042710 TI - Theoretical study on the reaction CX3 + SiH(CH3)3 (X = H, F). AB - Theoretical investigations are carried out on the multiple-channel reactions, CH(3) + SiH(CH(3))(3) -> products and CF(3) + SiH(CH(3))(3) -> products. The minimum energy paths (MEP) are calculated at the MP2/6-311 + G(d,p) level, and energetic information is further refined by the MC-QCISD (single point) method. The rate constants for major reaction channels are calculated by the canonical variational transition state theory (CVT) with small-curvature tunneling (SCT) correction over the temperature range 200-1500 K. The theoretical rate constants are in good agreement with the available experimental data and are found to be k(1a)(T) = 1.93 * 10(-24) T(3.15) exp(-1214.59/T) and k(2a)(T) = 1.33 * 10(-25) T(4.13) exp(-397.94/T) (in unit of cm(3) molecule(-1) s(-1)). Our calculations indicate that hydrogen abstraction channel from SiH group is the major channel due to the smaller barrier height among five channels considered. PMID- 22042711 TI - Polyvinylidene fluoride for proliferation and preservation of bovine corneal endothelial cells by enhancing type IV collagen production and deposition. AB - In this study, biomaterials with different hydrophobic properties including polyvinyl alcohol (PVA), poly(ethylene-co-vinyl alcohol) (EVAL), tissue culture polystyrene (TCPS), and polyvinylidene fluoride (PVDF) were examined in the bovine corneal endothelial cells (BCECs) culture system to elucidate their possible impact on clinical demand and scientific interest. It was found that BCECs were inhibited to attach onto the PVA surface. Conversely, relatively more hydrophobic biomaterials EVAL, TCPS, and PVDF successfully initiate BCEC adhesion. Compared to EVAL, cultured BCECs on TCPS and PVDF exhibited higher viability. Furthermore, fibroblastic transformation on EVAL and TCPS was observed at day 17, but BCECs maintained typical hexagonal shape on the PVDF surface at day 21. This phenomenon can be rescued by previously coating type IV collagen on TCPS but not on EVAL. In addition, when BCECs were cultured on PVDF, the expressions of gap junction connexin-43, differentiation marker N-cadherin, and tight junction ZO-1 were well-developed, resembling the physiological phenotypes. After examining the type IV collagen expression by Western blot analysis and protein absorption test, a possible explanation for the better proliferation and preservation of BCECs on the PVDF substrate is that PVDF is a bioactive substratum which enables BCECs to synthesize and reserve more extracellular matrix type IV collagen, paving an important way to provide a more preferential environment for BCEC cultures. Accordingly, promoting CEC growth effects after cell-biomaterial association may be applied to the tissue engineering of corneal endothelium. PMID- 22042712 TI - Alleviating emotional exhaustion in oncology nurses: an evaluation of Wellspring's "Care for the Professional Caregiver Program". AB - A high level of burnout has been demonstrated in oncologists, nurses, and other health professionals. Interventions developed in response demonstrate mixed results. Wellspring, a community cancer support organization, has developed a 1 day session called Care for the Professional Caregiver Program (CPCP) and has delivered it to over 700 healthcare workers. The present study assessed the effects of the CPCP on three groups of oncology nurses (pediatric, surgical, and general oncology staff) and one group of nurse managers. Subjects completed the Maslach burnout inventory (MBI), the General health questionnaire (GHQ) and the short form of the Marlowe-Crowne social desirability scale (M-C) prior to receiving the intervention. They then completed the MBI and GHQ at 1-month and 7 month follow-ups. Six months after the original session, a small subset of subjects was randomly selected to participate in a 1-day CPCP booster session. At baseline, one third of the nurses showed high burnout on the MBI. The nurses demonstrated a significant decrease in emotional exhaustion and an improvement on the GHQ, at the 1-month follow-up testing (p = 0.003 and 0.001, respectively) and 7-month follow-up testing (p = 0.002 and 0.001). The booster session proved difficult to deliver because of institutional scheduling problems due to nurse shortages, so only a small percentage (22%) of the sample participated; however, it was well received. Thus, the CPCP is effective in ameliorating emotional exhaustion, an intrinsic aspect of burnout. PMID- 22042713 TI - The role of alcohol dehydrogenase genes in head and neck cancers: a systematic review and meta-analysis of ADH1B and ADH1C. AB - Alcohol drinking is a major risk factor for head and neck cancer (HNC). This risk may be modified by alcohol dehydrogenase (ADH) genes, particularly ADH1B and ADH1C, that oxidise ethanol to its carcinogenic metabolite, acetaldehyde. A meta analysis was conducted to assess the association between ADH1B and ADH1C and HNC risk. Twenty-nine studies from 28 articles identified from a literature search were included. Summary odds ratios (meta-ORs) were generated using random effect models. A reduced risk for HNC was associated with carrying the ADH1B*2 and ADH1C*1 alleles that confer faster metabolism of ethanol to acetaldehyde [meta-OR ADH1B, 0.50; 95% confidence interval (CI): 0.37-0.68, 13 studies; meta-OR ADH1C, 0.87; 95% CI: 0.76-0.99, 22 studies]. ADH1B*2 and ADH1C*1 alleles appear to be protective for HNC, possibly due to: (i) decreasing the opportunity for oral microflora to produce acetaldehyde locally from a prolonged systemic circulation of ethanol, (ii) preventing ethanol from acting as a solvent for other carcinogens, and (iii) decreasing the amount of ethanol a person consumes since a consequent peak in systemic acetaldehyde could cause discomfort. These results underscore the importance of ADH1B and ADH1C in the association between alcohol consumption and the risk for HNC. PMID- 22042714 TI - Difference in susceptibility to morphological changes in the nucleus to aneugens between p53-competent and p53-abrogated lymphoblastoid cell lines (TK6 and NH32 cells) in the in vitro micronucleus assay. AB - We previously reported that the proportion of large-size micronuclei (MN) can be a reliable parameter to discriminate aneugens from clastogens in the in vitro MN assay using Chinese hamster lung cells. The frequencies of polynuclear (PN) and mitotic (M) cells are also supposed to be useful parameters for the same purpose since they are known to be increased by aneugens. In the present study, we investigated whether morphological observations of the cell nucleus can be applied for the in vitro MN assay using the p53-competent human lymphoblastoid cell line, TK6 cells. Our present MN assay with six clastogens and six aneugens revealed that the frequencies of large-size MN or PN cells cannot distinguish aneugens from clastogens, while the frequencies of M cells can distinguish them, suggesting that the M-cell frequency is a recommended parameter to determine a mode of action for MN induction in the in vitro MN assay using TK6 cells. Our further investigation using p53-null mutant NH32 cells showed that the frequencies of large-size MN or PN cells induced by aneugen treatments were higher than those in TK6 cells but not by clastogen treatments. These findings suggest that p53 abrogation promotes the susceptibility for morphological changes in the nucleus to aneugens and that morphological observation of the cell nucleus including size-classifying MN counting could distinguish aneugens from clastogens in the MN assay using NH32 cells. PMID- 22042715 TI - Prevalence of scrotal calculi and their relationship with pain. AB - PURPOSE: The purpose of this study was to determine the frequency of scrotal calculi in men referred for scrotal ultrasonography (US), to identify any associated pathologies, and to investigate if any relationship exists between scrotal lithiasis and pain. MATERIALS AND METHODS: This was a retrospective study in which 4084 scrotal US examinations in 3435 men were evaluated. Scrotal US was performed using a high-frequency linear transducer. Forty patients were questioned as to whether scrotal pain was present. Patients were asked to grade their scrotal pain intensity using the Numerical Rating Scale. RESULTS: Sixty seven of the 3435 patients with scrotal US examinations had scrotal calculi with a mean size of 3.7 +/- 1.4 mm (range, 1.6-7 mm). Twenty patients with scrotal calculi had no scrotal pain. Nine patients with scrotal pain (22.5%) had no US or clinical abnormalities except scrotal calculi. CONCLUSION: The frequency of scrotal calculi was 1.95%. Approximately one-quarter of patients with scrotal calculi and pain had no additional abnormalities. Therefore, scrotal calculi should be considered in the differential diagnosis of scrotal pain. PMID- 22042716 TI - Value-based care in the management of spinal disorders: a systematic review of cost-utility analysis. AB - BACKGROUND: Spinal disorders are a major cause of disability and compromise in health-related quality of life. The direct and indirect costs of treating spinal disorders are estimated at more than $100 billion per year. With limited resources, the cost-utility of interventions is important for allocating resources. QUESTIONS/PURPOSES: We therefore performed a systematic review of the literature on cost-utility for nonoperative and operative interventions for treating spinal disorders. METHODS: We searched four databases for cost-utility analysis studies on low back pain management and identified 1004 items. The titles and abstracts of 752 were screened before selecting 27 studies for inclusion; full texts of these 27 studies were individually evaluated by five individuals. RESULTS: Studies of nonoperative treatments demonstrated greater value for graded activity over physical therapy and pain management; spinal manipulation over exercise; behavioral therapy and physiotherapy over advice; and acupuncture and exercise over usual general practitioner care. Circumferential fusion and femoral ring allograft had greater value than posterolateral fusion and titanium cage, respectively. The relative cost-utility of operative versus nonoperative interventions was variable with the most consistent evidence indicating superior value of operative care for treating spinal disorders involving nerve compression and instability. CONCLUSION: The literature on cost utility for treating spinal disorders is limited. Studies addressing cost-utility of nonoperative and operative management of low back pain encompass a broad spectrum of diagnoses and direct comparison of treatments based on cost-utility thresholds for comparative effectiveness is limited by diversity among disorders and methods to assess cost-utility. Future research will benefit from uniform methods and comparison of treatments in cohorts with well-defined pathology. PMID- 22042717 TI - Does previous reconstructive surgery influence functional improvement and deformity correction after periacetabular osteotomy? AB - BACKGROUND: The Bernese periacetabular osteotomy (PAO) is commonly used to surgically treat residual acetabular dysplasia. However, the degree to which function and radiographic deformity are corrected in patients with more severe deformities that have undergone previous reconstructive pelvic or femoral osteotomies is unclear. QUESTIONS/PURPOSES: We evaluated hip pain and function, radiographic deformity correction, complications, reoperations, and early failures (conversion to THA) associated with PAO in hips treated with previous reconstructive hip surgery. METHODS: We retrospectively reviewed 63 patients who had undergone 67 PAOs after a previous reconstructive hip procedure. We compared preoperative hip scores and radiographic parameters with postoperative values at most recent followup. We recorded complications, need for nonarthroplasty revision surgery, and failures. Minimum followup was 2 years. RESULTS: Five of the 67 hips (8%) were converted to THA between 24 and 118 months. The average followup for the remaining 62 hips was 60 months (range, 24-147 months). The average Harris hip score improved 11 points, and postoperatively, 83% of the hips had pain component scores of greater than 30 (none, slight, or mild pain). Radiographically, there were improvements in lateral center-edge angle (25 degrees ), anterior center-edge angle (23 degrees ), Tonnis angle (17 degrees ), and medialization of the hip center (8 mm). Complications occurred in 13 hips (19%). Seven hips (10%) underwent a subsequent surgical procedure to address residual pain or deformity. CONCLUSIONS: PAO performed after previous reconstructive hip surgery improves hip function and corrects residual dysplasia deformities. These procedures are inherently more complex than primary PAO and are associated with a considerable risk of perioperative complications, reoperations, and early treatment failures. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22042718 TI - Tail architecture and function of Cebupithecia sarmientoi, a Middle Miocene platyrrhine from La Venta, Colombia. AB - Cebupithecia sarmientoi, an early pitheciine from the Middle Miocene of La Venta, Colombia, preserves an almost complete caudal vertebral sequence (18 vertebrae). Behavioral reconstructions for this taxon based on appendicular elements suggest a locomotor profile similar to that of Pithecia for which vertical clinging postures and leaping behavior are frequently adopted. General tail morphology suggests some similarity with prehensile-tailed Cebus in the proximal tail region, although overwhelming similarity with nonprehensile-tailed Pithecia is evident in the distal tail region. Indices of caudal muscle attachment sites show marked similarities to nonprehensile-tailed platyrrhines, especially Pithecia. However, the cortices of Cebupithecia caudal vertebral bodies are thicker than those of most other nonprehensile-tailed New World primates. Mechanically, this would provide high resistance to bending and torsional stresses, falling within the range exhibited by prehensile-tailed monkeys. These results suggest that Cebupithecia may have employed its tail differently than most nonprehensile tailed platyrrhines living today, behaviors that possibly involved tail-bracing or twisting during hindlimb (pedal grasping) suspensory behaviors. Such behaviors may serve as a preadaptive model for the full-fledged evolution of below-branch tail suspension and prehensility seen in other New World primates. PMID- 22042719 TI - Theoretical investigation on redox-switchable second-order nonlinear optical responses of push-pull Cp*CoEt2C2B4H3-expanded (metallo)porphyrins. AB - The second-order nonlinear optical (NLO) properties of the Cp*Co(C(2)H(5))(2)C(2)B(4)H(3)-expanded (metallo)porphyrins (Cp* = C(5)Me(5)) have been investigated by using ab inito RHF and density functional theory (DFT) methods. The investigation shows that the compound with expand porphyrin possesses remarkable large molecular hyperpolarizability beta(tot) value, ~414.1 * 10(-30) esu (at LC-omegaPBE level), and might be an excellent second-order NLO material. From the character of charge transfer (CT) transition, it indicates that the -Cp*Co(C(2)H(5))(2)C(2)B(4)H(3) acts as an electron donor in this kind of systems. As a result of the redox behavior on expanded (metallo)porphyrin, the redox switching character of the NLO responses for the systems 2a-4a has also been studied. The results show that the beta(tot) values of reduced forms are larger than that of neutral ones. Furthermore, the time-dependent DFT calculation illustrates that reduced forms have a significant difference on the CT patterns versus neutral ones. The present investigation provides insight into the comparison with DFT results on estimating first hyperpolarizability and the NLO properties of the series of push-pull compounds. PMID- 22042720 TI - A new approach to dose estimation and in-phantom figure of merit measurement in BNCT by using artificial neural networks. AB - In-phantom figures of merit of the radiobiological dose distribution are the main criteria for evaluation of the boron neutron capture therapy (BNCT) plan and neutron beam evaluation. Since in BNCT there are several reactions, which contribute to the total dose of the tissue, the calculation of the dose distribution is complicated and requires lengthy and time-consuming simulations. Any changes in the beam shaping assembly (BSA) design would lead to the change of the neutron/gamma spectrum at exit of therapeutic window. As a result of any changes in the beam spectrum, the dose distribution in the tissue will be altered; therefore, another set of lengthy and time-consuming simulations to recalculate the dose distribution would have to be performed. This study proposes a method that applies artificial neural network (ANN) for quick dose prediction in order to avoid lengthy calculations. This method allows us to estimate the depth-dose distribution and in-phantom figures of merit for any energy spectrum without performing a complete Monte Carlo code (MCNP) simulation. To train the ANNs for modeling the depth-dose distribution, this study used a database containing 500 simulations of the neutron depth-dose distribution and 280 simulations of the gamma depth-dose distribution. The calculations were carried out by the MCNP for various mono-energetic neutrons, ranging from thermal up to 10 MeV energy and 280 gamma energy group, ranging from 0.01 MeV up to 20 MeV, through the SNYDER head phantom which is located at the exit of the BSA. The trained ANN was capable of establishing a map between the neutron/gamma beam energy and the dose distribution in the phantom as an input and a response, respectively. The current method is founded upon the observation that the dose which is released by the beam of composite energy spectrum can be decomposing into the various energy components which make the neutron/gamma spectrum. Therefore, in this procedure the neutron/gamma energy spectrum was converted into several energy groups and dose response of each group was predicted by the trained ANN. Total dose distribution of the entire spectrum is equal to summation of dose response of each group. If the neutron/gamma spectrum as an input changes, the dose response of that as an output can be predicted by the trained ANN in no time rather than hours or days by MCNP simulations. To check the validity of this method, this study compared full calculation of the depth-dose distribution with prediction of ANN for that. The result of this comparison shows that artificial neural networks model the dose distribution in phantom successfully and result in a great accurate prediction. PMID- 22042721 TI - Impact of heart failure on hip fracture outcomes: a population-based study. AB - BACKGROUND: Hip fracture and heart failure are becoming more prevalent conditions in hospitalized patients. Despite differences in postoperative outcomes from other intermediate risk procedures, guidelines classify hip fracture repair as an intermediate risk operation. OBJECTIVE: This population-based study sought to examine the prevalence and incidence of heart failure in hip fracture patients. DESIGN, SETTING, AND PATIENTS: We conducted a population-based historical cohort study of 1116 Olmsted County, MN residents undergoing 1212 hip surgeries from 1988 through 2002. Data were obtained through medical record review. Heart failure was defined by Framingham criteria. RESULTS: The prevalence of preoperative heart failure in our study population was 27% (327 of 1212 cases). Those with preoperative heart failure demonstrated longer lengths of stay, were more often discharged to a skilled facility, and had higher inpatient mortality rates. Rates of postoperative heart failure were 6.7% at seven days and 21.3% at one year. Postoperative heart failure was more common among those with preoperative heart failure (HR 3.0), and those with preoperative heart failure demonstrated higher postoperative mortality rates. Men had a higher risk of postoperative mortality compared to women. Overall survival was lowest among those with both preoperative and postoperative heart failure. CONCLUSIONS: Heart failure represents a common and serious perioperative condition in hip fracture patients. Hip fracture patients with and without heart failure carry higher postoperative risk than guidelines may suggest. Future work must focus on the perioperative management of hip fracture patients with and without heart failure to mitigate postoperative morbidity. PMID- 22042722 TI - Role of aging on innate responses to viral infections. AB - Older people exhibit increased morbidity and mortality after viral infections than younger people. Additionally, vaccines are less protective in older people than in younger people. As the immune system is critical for host defense to viral infections and for vaccine efficacy, the implications are that aging negatively affects immunity. The immune system is broadly categorized into adaptive and innate systems. The innate immune system acts as a first line of defense to pathogen invasion. In this review, I focus on how aging affects the innate immune response to viral infection. PMID- 22042723 TI - Higher Healthy Eating Index-2005 scores are associated with better physical performance. AB - BACKGROUND: Little is known regarding the relationship between overall diet quality and physical performance among older adults. We examined the association between overall diet quality, as measured by the US Department of Agriculture's Healthy Eating Index-2005 (HEI-2005), and physical performance, as measured by gait speed (n = 2,132) and knee extensor power (n = 1,392), among adults aged 60 years or older. METHODS: Using data from the 1999-2002 National Health and Nutrition Examination Survey, multiple linear regression models controlling for age, gender, race/ethnicity, education, smoking status, comorbidities, medication use, cognitive function, body mass index, and physical activity were used in the analyses. RESULTS: After adjusting for age, gender, race/ethnicity, education, and smoking status, total HEI-2005 scores were positively associated with both gait speed (p for trend = .02) and knee extensor power (p for trend = .05). Older adults with higher HEI-2005 scores had a faster gait speed (p = .03 for both Quartile 3 and Quartile 4 vs quartile 1) compared with those with HEI-2005 scores in the lowest quartile. Those with HEI-2005 scores in Quartile 4 had a greater knee extensor power compared with those with HEI-2005 scores in the lowest quartile (p = .04). The associations between HEI-2005 scores and physical performance remained after further adjustment for comorbidities, medication use, cognitive function, and body mass index. However, the associations were no longer statistically significant after further adjustment for physical activity. CONCLUSION: Adherence to overall dietary recommendations is associated with better physical performance among older adults. PMID- 22042724 TI - Balance between macronutrients affects life span and functional senescence in fruit fly Drosophila melanogaster. AB - It has recently been demonstrated that as the ratio of protein to carbohydrate (P:C) in the diet declines, life span increases in Drosophila. Here we explored how extremely low dietary ratios of protein to carbohydrate affected longevity and a selection of variables associated with functional senescence. An increase in P:C ratio from 1:57 to 1:20 shortened life span by increasing age-dependent mortality; whereas a further decline in P:C from 1:57 to 1:95 caused a modest decrease in life span. Female flies consuming the 1:20 and 1:38 diets laid more eggs than those consuming the lower P:C diets. Flies fed diets with higher ratios were more resistant to heat stress. Flies consuming the diets with lowest P:C ratios needed more time to restore activity after paralysis. Our study has therefore extended to very low P:C ratios available data demonstrating that dietary P:C ratio affects life span, fecundity and heat stress resistance, with fecundity and heat stress responses showing the opposite trend to life span. PMID- 22042725 TI - Completion and return of fall diaries varies with participants' level of education, first language, and baseline fall risk. AB - BACKGROUND: Consensus guidelines recommend the use of prospective fall diaries in studies of fall rates. We sought to determine the characteristics associated with return and successful completion of a falls diary and whether characteristics such as gender, education level, native language, income, and falls risk influenced self-reported fall rates. METHODS: Two hundred and seventy people aged 65 years and older participating in a randomized controlled trial evaluating two exercise programmes. Fall diaries were collected for 6 months, then evaluated for correct completion and falls reported. RESULTS: An increasing risk of falls was associated with a reducing odds of returning diaries (odds ratio for a one unit increase in Falls Risk Assessment Tool score 0.71, 95% confidence interval 0.53 0.96). Native English speakers were more likely to complete more than half the diaries correctly (odds ratio 2.63, 95% confidence interval 1.20-5.75). CONCLUSIONS: Problems arise in the correct completion of falls diaries among those for whom English is not their first language. Diaries may underreport the rate of falls as those at higher risk were less likely to return diaries but more likely to report falls. Careful consideration should be given to the analysis of falls diaries as missing data are unlikely to be missing completely at random. We recommend additional training in the use of falls diaries for these groups or the utilization of simpler instruments. PMID- 22042726 TI - Mind your errors: evidence for a neural mechanism linking growth mind-set to adaptive posterror adjustments. AB - How well people bounce back from mistakes depends on their beliefs about learning and intelligence. For individuals with a growth mind-set, who believe intelligence develops through effort, mistakes are seen as opportunities to learn and improve. For individuals with a fixed mind-set, who believe intelligence is a stable characteristic, mistakes indicate lack of ability. We examined performance monitoring event-related potentials (ERPs) to probe the neural mechanisms underlying these different reactions to mistakes. Findings revealed that a growth mind-set was associated with enhancement of the error positivity component (Pe), which reflects awareness of and allocation of attention to mistakes. More growth minded individuals also showed superior accuracy after mistakes compared with individuals endorsing a more fixed mind-set. It is critical to note that Pe amplitude mediated the relationship between mind-set and posterror accuracy. These results suggest that neural mechanisms indexing on-line awareness of and attention to mistakes are intimately involved in growth-minded individuals' ability to rebound from mistakes. PMID- 22042727 TI - A face only an investor could love: CEOs' facial structure predicts their firms' financial performance. AB - Researchers have theorized that innate personal traits are related to leadership success. Although links between psychological characteristics and leadership success have been well established, research has yet to identify any objective physical traits of leaders that predict organizational performance. In the research reported here, we identified leaders' facial structure as a specific physical trait that correlates with organizational performance. Specifically, we found that firms whose male CEOs have wider faces (relative to facial height) achieve superior financial performance. Decision-making dynamics within a firm's leadership team moderate this effect, such that the relationship between a given CEO's facial measurements and his firm's financial performance is stronger in firms with cognitively simple leadership teams. PMID- 22042728 TI - Big time is not always long: numerical magnitude automatically affects time reproduction. AB - To reproduce the duration of an event precisely, one needs to represent the temporal information without being influenced by other magnitude attributes (e.g., size) of the event. In the present study, however, task-irrelevant numerical magnitude automatically affected participants' reproduction of the duration of a stimulus. In Experiment 1, participants made key-press responses to reproduce the duration of numbers. Reproduced durations were shorter for small numbers (e.g., 1) than for large numbers (e.g., 9). In contrast, in Experiment 2, participants' reproductions of a standard duration were longer when their key press response was accompanied by visual presentation of a small number than when it was accompanied by presentation of a large number. These results clearly demonstrate that number-time interference extends beyond simple mapping between stimulus categories and response alternatives. The findings support the notion that either a common magnitude representation or closely connected magnitude representations underlie numerical and temporal processing. PMID- 22042729 TI - Cardiac neoplasms and pseudotumors: imaging findings on multidetector CT angiography. AB - A wide spectrum of masses can affect the heart, ranging from non-malignant entities, such as thrombi, to aggressive primary cardiac tumors, such as angiosarcomas. Echocardiography and magnetic resonance imaging have traditionally formed the mainstay techniques for assessing these lesions. Recent technological advances have seen ECG-gated multi-detector computed tomography (MDCT) emerge as a valuable complimentary technique for assessing a suspected cardiac mass because it provides high spatial resolution, fast acquisition times, and the ability to definitively characterize fat and calcification. This article reviews the MDCT features of the spectrum of cardiac neoplasms and pseudotumors and describes important diagnostic criteria. PMID- 22042730 TI - Successful treatment of delayed aortobifemoral graft thrombosis with manual aspiration thrombectomy. AB - We present a 67-year-old man who had undergone aortobifemoral synthetic graft surgery one year earlier. The patient experienced thrombosis of the graft nine months after the operation, and thrombectomy of the graft was planned. However, the patient refused to undergo repeat surgery for thrombus removal and was referred to our center for possible endovascular treatment. We treated the patient with percutaneous aspiration thrombectomy. The thrombi were chronic in nature but could be removed with minimal residue in any part of the graft by using repeated aspiration thrombectomy with 7 F guiding catheters. Underlying stenosis of both distal graft anastomoses was treated with percutaneous balloon angioplasty, and a self-expanding stent was deployed on the right distal anastomosis. A small fragment of thrombus embolized to the right popliteal artery and was removed with aspiration thrombectomy through a second antegrade puncture on the right side. We believe this is the first report of aspiration thrombectomy for an aortobifemoral graft thrombosis. The method was successful despite the chronic nature of the thrombi. Manual aspiration thrombectomy with largebore guiding catheters can be used as an effective recanalization method for delayed aortobifemoral graft occlusion and could be regarded as a good alternative technique to surgical thrombectomy in selected patients. PMID- 22042731 TI - The impact of pre-procedural waiting period and anxiety level on pain perception in patients undergoing transrectal ultrasound-guided prostate biopsy. AB - PURPOSE: To investigate the effect of pre-procedural waiting period and anxiety level on pain perception during transrectal ultrasound-guided prostate biopsy. MATERIALS AND METHODS: Sixty patients who had undergone transrectal ultrasound guided prostate biopsy were enrolled in this prospective study. The subjects were asked to fill out the State-Trait Anxiety Inventory Scale-1 to measure the level of state anxiety at three times: 1) at the time of the procedure request, 2) before the procedure, and 3) before getting the result. Just after biopsy, the patients were asked to fill out a visual analog scale to evaluate pain perception resulting from the biopsy. RESULTS: The mean pre-procedural level of state anxiety score was well correlated with the visual analog scale score (r=0.498; P < 0.001). The mean level of state anxiety scores before biopsy (39.7+/-9.4) and before getting the result (39.9+/-8.4) were significantly higher than the mean level of state anxiety score when the procedure was requested (31.4+/-7.9) (P < 0.001 for both). The patient group was divided into two subgroups according to the waiting time between the request and the procedure itself; the cut-off value between the short and long groups was 10 days. The difference between the mean visual analog scale scores from transrectal ultrasound-guided prostate biopsy patients with the short (n=23, 1.49+/-0.95) and long (n=37, 2.35+/-1.12) waiting periods was statistically significant (P = 0.003). CONCLUSION: In conclusion, performing the transrectal ultrasound-guided prostate biopsy procedure as soon as possible and using more effective anesthetic methods, especially for patients with high level of state anxiety scores, may have a positive impact on patient tolerance. PMID- 22042732 TI - Resveratrol ameliorates the deleterious effect of severe acute pancreatitis. AB - Resveratrol (RES) is a traditional Chinese herbal medicine having anti inflammatory properties. We sought to explore the role of RES in intestinal injury during severe acute pancreatitis (SAP) in a rat model study. For this purpose, RES-treated and sham-operated (SO) SAP rat models were established, and SAP was induced in rats by injecting 4% sodium taurocholate into the biliary pancreatic duct. In the RES group, RES was infused intravenously immediately after the SAP induction in rats; SO group served as controls. Histopathological analysis, determination of tissue levels of superoxide dismutase (SOD) and malondialdehyde (MDA) and serum levels of TNF-alpha as well as ICAM-1 and VCAM-1 expression were carried out at 3, 6, and 12 h following SAP induction. The data show that following SAP induction, SOD levels decreased and MDA levels increased along with ICAM-1 and VCAM-1 expression in the intestine. Serum TNF-alpha levels increased in the SAP group. Importantly, RES treatment significantly reversed all the pathological changes. In conclusion, this study confirmed the anti inflammatory properties of RES and demonstrated the prevention of injury to the intestinal barrier in the rat SAP model. PMID- 22042733 TI - Mechanoreceptivity of prehensile tail skin varies between ateline and cebine primates. AB - Prehensile tails evolved independently twice in primates: once in the ateline subfamily of platyrrhine primates and once in the genus Cebus. Structurally, the prehensile tails of atelines and Cebus share morphological features distinguishing them from nonprehensile tails (e.g., robust and strong caudal vertebrae, well developed lateral tail musculature, etc.). However, because of their independent evolutionary histories, the prehensile tails of atelines exhibit some differences from the Cebus prehensile tail. Ateline tails are relatively longer than those of Cebus, and they have less well-developed extensor compartment musculature. However, perhaps the most obvious difference is the distinctive hairless friction pad on the ventrodistal surface of the ateline tail; the tail of Cebus is completely covered in hair. This study documents the presence of four epicritic histologic mechanoreceptors in the friction pad of atelines: Meissner's corpuscles, Pacinian corpuscles, Ruffini corpuscles, and Merkel discs. Ruffini corpuscles and Merkel cells were also identified in the ventrodistal skin of the Cebus tail. However, Meissner's and Pacinian corpuscles (not typically associated with hairy skin) were not found in Cebus. Cebus was also compared to its closest living sister taxon, nonprehensile-tailed Saimiri, in which genus only Ruffini corpuscles are observed (no Merkel discs). The differences in mechanoreceptor type and morphology are attributed to the contrasting behavioral and tactile demands of the tail as it is used in posture and locomotion, which also distinguishes atelines from Cebus. PMID- 22042734 TI - Mechanism for the reaction of 2-naphthol with N-methyl-N-phenyl-hydrazine suggested by the density functional theory investigations. AB - For the first time the computed mechanisms for the novel reaction of 2-naphthol with N-methyl-N-phenylhydrazine, leading to 1-amino-2-naphthol (Tang et al., J Am Chem Soc 2008, 130, 5840), have been investigated using the density functional theory. Four distinct possible pathways were evaluated: two amination mechanisms with the attack of NH(2) group respectively at the alpha-position C1 and beta position C3 atoms of 2-naphthol (pathways 1 and 2) as well as two rearrangement processes with displacement of the phenolic hydroxyl group followed by the benzidine-like rearrangement at the alpha-position C1 and beta-position C3 atoms of 2-naphthol, respectively (pathways 3 and 4). Solvent effect has been tested based on the optimized geometries of the stationary points in solution at the B3LYP/PCM/6-31+G(d,p) level of theory with an averaged dielectric constant of binary solvent. Single-point energies of the optimized structures have been calculated using three hybrid density functionals, B3LYP, MPW3LYP, and B3PW91 with the 6-311++G(3df,2p) basis set. Our computed results clearly manifest that pathway 1 (alpha-amination) has the highest possibility to occur, with the Gibbs free energies being lower by 6 to 20 kcal/mol compared with the other three pathways, which leads to 1-amino-2-naphthol and N-methylaniline as products. It is in excellent agreement with the experimental observation. PMID- 22042735 TI - CURB-65 and SMRT-CO in the prediction of early transfers to the intensive care unit among patients with community-acquired pneumonia initially admitted to a general ward. AB - BACKGROUND: No study has assessed the ability of pneumonia severity scores to identify the risk for early intensive care unit (ICU) transfer in patients with community-acquired pneumonia (CAP) admitted to general wards (GW). We aimed to compare the ability of CURB-65 (confusion, urea level, respiratory rate, blood pressure, and age >=65 years) and SMRT-CO (systolic blood pressure, multilobar chest radiography involvement, respiratory rate, tachycardia, confusion, and oxygenation) scores to predict early ICU transfers in these patients. DESIGN: Retrospective, case-control study. Cases were defined as patients admitted to GW with CAP that required ICU transfer within 48 hours. Controls were defined as patients admitted to GW with CAP that did not require ICU transfer. CURB-65 and SMRT-CO scores were calculated on presentation to emergency department (ED), and upon admission to GW. Composite scores were calculated combining data from ED and GW. Sensitivities, specificities, likelihood ratios, and areas-under-the-curve (AUC) were calculated for each score. RESULTS: From 2003 to 2009, 115 cases and 345 controls were identified. Both groups had similar baseline characteristics. Composite scores combining data from ED and GW had better sensitivity and AUC than scores calculated only with ED or GW data (P < 0.001). A composite SMRT-CO score >=2 had 76.5% (95% CI, 67.7 to 83.9) sensitivity, 67.5% (95% CI, 62.3 to 72.4) specificity, and 0.81 (95% CI, 0.77 to 0.85) AUC. A composite CURB-65 score >=3 had 36.5% (95% CI, 27.7 to 46.0) sensitivity, 86.3% (95% CI, 82.3 to 89.8) specificity, and 0.66 (95% CI, 0.60 to 0.72) AUC to predict early ICU transfers. Composite SMRT-CO had higher sensitivity and AUC (P < 0.001) than composite CURB 65. CONCLUSIONS: Composite SMRT-CO had a better combination of sensitivity and specificity than CURB-65 for predicting early ICU transfers. Prospective studies to confirm our findings are needed. PMID- 22042736 TI - SONNE: solar-based man-made carbon cycle and the carbon dioxide economy. PMID- 22042737 TI - Interleukin-1beta enhances cartilage-to-cartilage integration. AB - The failure of cartilages to fuse, particularly in the case of articular cartilage under conditions of repair is due to morphological and structural constraints of the tissue. Factors that impede integration include, non vascularisation, low cellularity, and proteoglycan in the surrounding extracellular matrix acting as a natural barrier to cellular migration. We hypothesised that brief activation of a catabolic cascade by cytokines followed by culture under anabolic conditions would promote tissue fusion in a ring-disk model of cartilage integration. Our results show that transient exposure to 10 ng mL(-1) interleukin-1beta, followed by two weeks post-culture under anabolic conditions, enhanced cartilage-cartilage integration compared to untreated explants. Quantitative PCR analysis of catabolism-related genes ADAMTS4 and MMP13 showed both were transiently upregulated and these findings correlated with evidence of extracellular matrix remodelling. At the level of histology, we observed chondrocytes readily populated the interfacial matrix between fused explants in interleukin-1beta treated explants, whereas in control explants this region was relatively acellular in comparison. Catabolic cytokine treated explants exhibited 29-fold greater adhesive strength (0.859 MPa versus 0.028 MPa, P < 0.05) than untreated counterparts. Collectively, our results demonstrate that a single short catabolic pulse followed by an anabolic response is sufficient to generate mechanically robust, integrative cartilage repair. PMID- 22042738 TI - Physical properties of fruit and seeds ingested by primate seed predators with emphasis on sakis and bearded sakis. AB - Several primate radiations exhibit dental adaptations that enable them to gain access to seeds embedded in well-protected fruit. To a database drawn from published sources in which hardness of fruit and seeds were tested in the field, we added an additional 100+ species of plants used as resources by pitheciin primates (specifically, South American white-faced sakis (Pithecia pithecia) and bearded sakis (Chiropotes spp.). This sample allowed us to compare hardness of fruit and seeds and deduce the relative incisive and masticatory capability of several primate taxa (New World monkeys, Old World monkeys, prosimians and chimpanzees). Pitheciins have very well developed and highly modified anterior dentition that they use in gaining access to mechanically-protected fruit. In addition, their molars bear thin, but decussated enamel that protects the tooth enamel from crack proliferation. The ability of sakis (Chiropotes spp. and Pithecia pithecia) to open fruit orally was comparable to larger-bodied Old World seed predators-Lophocebus and Cercocebus. But, baboons and chimpanzees masticate seeds that are two to three orders of magnitude harder than sakis or mangabeys. In spite of their puncture abilities, ~40% of foods ingested by pitheciins were in the range of a ripe fruit eater (Ateles paniscus). This raises the possibility that pitheciins exemplify Liem's paradox, that is, "that phenotypic specialization [is] not accompanied by ecological specialization" (Robinson and Wilson, 1998:224). Last, we examined the possibility that seeds may serve as fallback resources for primate seed predators. While pericarp hardness may vary seasonally for some seed predators (e.g., mangabeys), our data on bearded sakis and white-faced sakis suggest that seeds are their primary resources year round and pericarp hardness is unrelated to seasonal variation in rainfall. Pitheciins evolved specialized dentition that affords them access to relatively abundant and high-quality resources, a feeding strategy that results in minimal variation in resource availability seasonally. PMID- 22042739 TI - Improving the discharge process by embedding a discharge facilitator in a resident team. AB - BACKGROUND: Hospital discharges are vulnerable periods for patient safety, especially in teaching hospitals where discharges are done by residents with competing demands. We sought to assess whether embedding a nurse practitioner on a medical team to help physicians with the discharge process would improve communication, patient follow-up, and hospital reutilization. METHODS: A 5-month randomized controlled trial was conducted on the medical service at an academic tertiary-care hospital. A nurse practitioner was randomly assigned to 1 resident team to complete discharge paperwork, arrange follow-up appointments and prescriptions, communicate discharge plans with nursing and primary care physicians, and answer questions from discharged patients. RESULTS: Intervention patients had more discharge summaries completed within 24 hours (67% vs. 47%, P < 0.001). Similarly, they had more follow-up appointments scheduled by the time of discharge (62% vs. 36%, P < 0.0001) and attended those appointments more often within 2 weeks (36% vs. 23%, P < 0.0002). Intervention patients knew whom to call with questions (95% vs. 85%, P = 0.003) and were more satisfied with the discharge process (97% vs. 76%, P < 0.0001). Attending rounds on the intervention team finished on time (45% vs. 31%, P = 0.058), and residents signed out on average 46 minutes earlier each day. There was no significant difference between the groups in 30-day emergency department visits or readmissions. CONCLUSIONS: Helping resident physicians with the discharge process improves many aspects of discharge communication and patient follow-up, and saves residents' time, but had no effect on hospital reutilization for a general medicine population. PMID- 22042740 TI - A modified technique of pancreaticojejunostomy after pancreatoduodenectomy: a preliminary experience. AB - Pancreatoduodenectomy currently represents the treatment of choice for resectable pancreatic and periampullary malignant tumours, symptomatic chronic pancreatitis, duodenal cystic dystrophy, large adenomas, diverticula and benign periampullary tumours. Pancreato-jejunostomy failure remains the main complication following pancreatoduodenectomy, even leading to death. To improve the safety of this anastomosis, a modified technique of pancreato-jejunal anastomosis with posterior double-layer suture and Wirsung duct evagination is proposed. We report our experience in eight consecutive patients (4 females, 4 males; average age 66, range 57-74) undergoing Traverso-Longmire pylorus-preserving pancreatoduodenectomy using Wirsung duct evagination and posterior double-layer suture technique. There was no mortality; the post-operative recovery was uneventful with no pancreatic anastomotic leakage. The mean post-operative stay was 15 days (range 12-19). This proposed procedure could be considered an additional opportunity in the performance of a pancreato-enteric anastomosis, yielding good results and preserving from post-operative pancreatic ductal obstruction. PMID- 22042741 TI - A comparison of new bone formation in patients with ankylosing spondylitis and patients with diffuse idiopathic skeletal hyperostosis: a retrospective cohort study over six years. AB - OBJECTIVE: Ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) are both characterized by new bone formation in the spine but presumably have a different pathogenesis. This study was undertaken to compare the natural course of new bone formation in AS and DISH. METHODS: Lateral radiographs of the cervical and lumbar spine from AS and DISH patients obtained at >=2 time points within 6 years were analyzed to quantify osteophyte development. Radiographs were scored in a blinded manner by 2 readers using the modified Stoke AS Spine Score (mSASSS). Bone spurs were categorized as having an angle of <45 degrees or >45 degrees . RESULTS: AS patients (n = 146) were younger than DISH patients (n = 141) (mean +/- SD 54.2 +/- 12.3 years versus 60.3 +/- 7.7 years). Symptom duration (mean +/- SD) was 23.6 +/- 11.2 years in AS patients and 21.6 +/- 12.4 years in DISH patients. The mSASSS at baseline was lower in DISH patients (mean +/- SD 14.3 +/- 6.7) than in AS patients (20.5 +/- 14.5) but had increased by a similar amount at followup (3.3 +/- 4.2 versus 4.1 +/- 9.5). The mean mSASSS progression rate per year (1.3 units) was also comparable. The mean +/- SD number of syndesmophytes per patient was higher in AS (5.7 +/- 5.5) than DISH (2.7 +/- 2.8) patients (P < 0.001), while degenerative bone spurs (mean +/- SD) were more frequent in DISH (1.4 +/- 1.8) than AS (1.0 +/ 1.4) patients. AS patients developed more new bone spurs with an angle of <45 degrees than >45 degrees per patient (mean +/- SD 2.1 +/- 2.7 versus 0.6 +/- 0.9) (P < 0.001), while similar amounts of both types of bone formation were seen in DISH patients. CONCLUSION: Our findings indicate that the rates of new bone formation in AS and DISH are largely similar. Both groups show osteophyte development, but as expected, syndesmophytes are more frequent in AS patients while DISH patients have more degenerative bone spurs. The nature of the different mechanisms of bone formation needs further study. PMID- 22042742 TI - Is physical activity associated with low-risk health behaviours among 15-year-old adolescents in Finland? AB - AIMS: To investigate the associations between physical activity and the pattern of risk health behaviour consisting of smoking, alcohol consumption, snuff (snus), cannabis, and condom use among 15-year-old adolescents, taking their educational aspirations and family affluence into account. METHODS: The data were collected in the Health Behaviour in School-aged Children (HBSC) study in Finland in 2006. Standardised questionnaires were issued at schools to a 15-year-old nationally representative sample, of which 84.5% (1710 pupils) participated. Logistic regression analysis was used to explore the associations between physical activity, pattern of risk health behaviour, family affluence, and educational aspirations. Separate models for daily moderate-to-vigorous physical activity (MVPA) and leisure-time physical activity (LTPA) were tested. Multi level analysis was performed in order to control the nested characteristics of the data. RESULTS: Boys were significantly more physically active and used alcohol, cannabis, and snuff more often than girls. Girls had used a condom in their last intercourse less often than boys. The educational aspirations for higher education had the strongest association with the low-risk health behaviour, with the odds ratios in the MVPA model 3.30 (95% CI 2.41-4.55) for the boys and 3.46 (95% CI 2.56-4.67) for the girls. In the LTPA model, the corresponding odds ratios were 3.31 (95% CI 2.40-4.56) for the boys and 3.52 (95% CI 2.60-4.56) for the girls. CONCLUSIONS: Physical activity was not significantly associated with the low-risk health behaviour, whereas educational aspirations for higher education showed the strongest association. The results support the earlier studies indicating a social gradient in health-related behaviour already in adolescence. PMID- 22042743 TI - Calcium signaling in response to fluid flow by chondrocytes in 3D alginate culture. AB - Quantifying the effects of mechanical loading on the metabolic response of chondrocytes is difficult due to complicated structure of cartilage ECM and the coupled nature of the mechanical stimuli presented to the cells. In this study we describe the effects of fluid flow, particularly hydrostatic pressure and wall shear stress, on the Ca(2+) signaling response of bovine articular chondrocytes in 3D culture. Using well-established alginate hydrogel system to maintain spherical chondrocyte morphology, we altered solid volume fraction to change scaffold mechanics. Fluid velocities in the bulk of the scaffolds were directly measured via an optical technique and scaffold permeability and aggregate modulus was characterized to quantify the mechanical stimuli presented to cells. Ca(2+) signaling response to direct perfusion of chondrocyte-seeded scaffolds increased monotonically with flow rate and was found more directly dependent on fluid velocity rather than shear stress or hydrostatic pressure. Chondrocytes in alginate scaffolds responded to fluid flow at velocities and shear stresses 2-3 orders of magnitude lower than seen in previous monolayer studies. Our data suggest that flow-induced Ca(2+) signaling response of chondrocytes in alginate culture may be due to mechanical signaling pathways, which is influenced by the 3D nature of cell shape. PMID- 22042744 TI - Behavioral and ecological consequences of sex-based differences in gustatory anatomy in Cebus apella. AB - Fungiform papillae (FPs) are the only gustatory structures on the anterior tongue. Taste buds (TBs), which are located in FPs, house taste receptors. Each TB has a taste pore (TP) by which tastants are transmitted. In humans, FP and TB densities correlate with taste sensitivity and food preferences. Females have higher FP densities than males in Homo, Pan, and Cebus. Homo, Pan, and Cebus also have larger brains, slower ontogenetic development, and higher maternal investment in offspring compared to most primates. An increase in maternal investment places intense pressure on females to 1) obtain high-quality foods, and 2) detect potential toxins at low levels. This study examines sex differences in FPs and TPs (a TB surrogate) in 11 Cebus apella to test the hypothesis that higher FP density in females may be an adaptation specific to reproductive strategies of females. Tongues were imaged using an environmental scanning electron microscope; from these images FP surface area, FP density, TP count, and TP densities were calculated. We found that there were no significant differences between males and females in the number of TPs per FP. However, we did find that females do have larger FP surface areas and higher FP densities than males. The anatomical evidence indicates that females may have greater taste sensitivity than males because females have more FP than males. Future research on food preference and selection in Cebus is expected to show sex-specific behaviors similar to those observed in Homo and Pan. PMID- 22042745 TI - Health literacy and medication understanding among hospitalized adults. AB - BACKGROUND: Patients' ability to accurately report their preadmission medications is a vital aspect of medication reconciliation, and may affect subsequent medication adherence and safety. Little is known about predictors of preadmission medication understanding. METHODS: We conducted a cross-sectional evaluation of patients at 2 hospitals using a novel Medication Understanding Questionnaire (MUQ). MUQ scores range from 0 to 3 and test knowledge of the medication purpose, dose, and frequency. We used multivariable ordinal regression to determine predictors of higher MUQ scores. RESULTS: Among the 790 eligible patients, the median age was 61 (interquartile range [IQR] 52, 71), 21% had marginal or inadequate health literacy, and the median number of medications was 8 (IQR 5, 11). Median MUQ score was 2.5 (IQR 2.2, 2.8). Patients with marginal or inadequate health literacy had a lower odds of understanding their medications (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.34 to 0.84; P = 0.0001; and OR = 0.49; 95% CI, 0.31 to 0.78; P = 0.0001; respectively), compared to patients with adequate health literacy. Higher number of prescription medications was associated with lower MUQ scores (OR = 0.52; 95% CI, 0.36 to 0.75; for those using 6 medications vs 1; P = 0.0019), as was impaired cognitive function (OR = 0.57; 95% CI, 0.38 to 0.86; P = 0.001). CONCLUSIONS: Lower health literacy, lower cognitive function, and higher number of medications each were independently associated with less understanding of the preadmission medication regimen. Clinicians should be aware of these factors when considering the accuracy of patient-reported medication regimens, and counseling patients about safe and effective medication use. PMID- 22042746 TI - Substance P and norepinephrine modulate murine chondrocyte proliferation and apoptosis. AB - OBJECTIVE: Substance P (SP) and norepinephrine (NE) containing sensory and sympathetic nerve fibers innervate bone and fracture callus. They are involved in controlling vascularization and matrix differentiation during skeletal growth. Both types of nerve fibers are known to modulate growth and metabolic activity of osteoblasts and osteoclasts. The aim of this study was to understand the roles of SP and NE in chondrocyte metabolism and their impact on chondrocyte proliferation, apoptosis, and cell adhesion. METHODS: Primary costal chondrocytes were isolated from newborn mice. Micromass and monolayer cell culture regimens were used to analyze the effects of SP and NE on matrix formation, as determined by quantitative polymerase chain reaction and immunohistochemistry. The effects of SP and NE on proliferation, adhesion, and apoptosis of chondrocytes were determined by enzyme-linked immunosorbent assay, bromodeoxyuridine, TUNEL, and morphometric analyses. RESULTS: SP, neurokinin type 1 (NK-1) receptor, alpha adrenergic receptor (alpha-AR), and beta-AR were abundantly expressed in primary costal chondrocytes. Stimulation with SP or NE did not affect extracellular matrix formation with respect to types I, II, and IX collagen and aggrecan in micromass pellets. SP dose-dependently increased the rate of proliferation of chondrocytes via the NK-1 receptor, whereas NE decreased the apoptosis rate of chondrocytes by stimulating beta-AR. Both neurotransmitters induced the formation of focal adhesion contacts. CONCLUSION: Transmitters of sympathetic and sensory nerve fibers modulate the metabolic activity of chondrocytes. Endogenous SP, NK-1 receptor, and adrenoceptor expression in chondrocytes implicates as-yet-unknown, presumably trophic, functions of neurotransmitter for skeletal growth and might be of interest for use in cartilage regenerative medicine. PMID- 22042747 TI - Locomotor diversification in new world monkeys: running, climbing, or clawing along evolutionary branches. AB - Modern platyrrhines exhibit a remarkable diversity of locomotor and postural adaptations, which evolved along multiple trajectories since the initial immigration to the island continent of South America. We trace this diversification by reviewing the available paleontological and neontological data for postcranial morphology and ecological adaptation. Fossil platyrrhines are notably diverse, from the Oligocene Branisella, to the varied Patagonian early Miocene quadurpedal-leaping and quadrupedal-climbing fossils of disputed affinities, on through the rich middle Miocene Colombian quadurpedal-leaping forms. More recent taxa exhibit even more derived positional patterns, from the largest suspensory atelids in Pleistocene Brazil, to the remarkable Antillean radiation with suspensory forms and also semiterrestrial species, with postcranial morphology convergent on some Old World monkeys. Field studies of positional behavior of modern platyrrhines set the framework for a spectrum of locomotor adaptations. Central within this spectrum is a cluster of medium-sized species with generalized locomotion (quadrupedal-leaping). At opposite poles lie the more derived conditions: large-bodied species exhibiting locomotor specializations for climbing-suspension; small-bodied species exhibiting adaptations for claw climbing and leaping. This behavior-based spectrum of locomotor diversification is similarly evident in a morphology-based pattern, that is, that produced by the shape of the talus. The implications of the record of platyrrhine postcranial evolution for the competing hypotheses of platyrrhine phylogenetic patterns, the "long lineage hypothesis" and the "stem platyrrhine hypothesis," are considered. PMID- 22042748 TI - Biomechanical properties of the transverse carpal ligament under biaxial strain. AB - The transverse carpal ligament (TCL) influences carpal stability and carpal tunnel mechanics, yet little is known about its mechanical properties. We investigated the tissue properties of TCLs extracted from eight cadaver arms and divided into six tissue samples from the distal radial, distal middle, distal ulnar, proximal radial, proximal middle, and proximal ulnar regions. The 5% and 15% strains were applied biaxially to each sample at rates of 0.1, 0.25, 0.5, and 1%/s. Ligament thickness ranged from 1.22 to 2.90 mm. Samples from the middle of the TCL were thicker proximally than distally (p < 0.013). Tissue location significantly affected elastic modulus (p < 0.001). Modulus was greatest in the proximal radial samples (mean 2.8 MPa), which were 64% and 44% greater than the distal radial and proximal ulnar samples, respectively. Samples from the middle had a modulus that was 20-39% greater in the proximal versus more distal samples. The TCL exhibited different properties within different locations and in particular greater moduli were found near the carpal bone attachments. These properties contribute to the understanding of carpal tunnel mechanics that is critical to understanding disorders of the wrist. PMID- 22042749 TI - Comparison of montelukast and mometasone furoate in the prevention of recurrent nasal polyps. AB - BACKGROUND: The aim of our study was to compare the effects of montelukast and mometasone furoate nasal spray on the postoperative course of patients with nasal polyposis. PATIENTS AND METHODS: Fifty patients diagnosed with nasal polyposis between March 2006 and August 2007 were included in the study. All patients underwent bilateral endoscopic sphenoethmoidectomy and were randomized postoperatively into two groups. Group A (n = 25) received 10 mg montelukast per day and group B (n = 25) received 400 ug mometasone furoate nasal spray twice daily. All patients were followed up for 6 months. Sino-Nasal Outcome Test (SNOT) 22 scores, polyp grades, computerized tomography (CT) scores (Lund-Mackay), eosinophils in peripheral blood and polyp tissue were evaluated before and after surgery. RESULTS: There was a significant reduction in SNOT-22 scores in both groups throughout the study period. There was a significant difference in the recurrence rate between both groups with a marginal advantage of mometasone furoate nasal spray. Eosinophils in peripheral blood were found to be effective on the recurrence rate (p < 0.05). CONCLUSIONS: In conclusion, both drugs seem to have a complementary action and further studies are needed to determine which patients should receive which treatment. PMID- 22042750 TI - Behaviors of successful interdisciplinary hospital quality improvement teams. AB - BACKGROUND: Although interdisciplinary hospital quality improvement (QI) teams are both prevalent and associated with success of (QI) efforts, little is known about the behaviors of successful interdisciplinary QI teams. OBJECTIVE: We examined the specific behaviors of interdisciplinary QI teams in hospitals that successfully redesigned care for patients with ST-elevation myocardial infarction (STEMI) and reduced door-to-balloon times. DESIGN: Qualitative study. PARTICIPANTS: Researchers interviewed 122 administrators, providers, and staff in 11 hospitals with substantial improvements in door-to-balloon times. MEASUREMENTS: Using data from the in-depth qualitative interviews, the authors identified themes that described the behaviors of interdisciplinary QI teams in successful hospitals. RESULTS: Teams focused on 5 behaviors: (1) motivating involved hospital staff toward a shared goal, (2) creating opportunities for learning and problem-solving, (3) addressing the impact of changes to care processes on staff, (4) protecting the integrity of the new care processes, and (5) representing each involved clinical discipline effectively. CONCLUSIONS: The behaviors observed may enhance a QI team's ability to motivate the various disciplines involved, understand the care process they must change, be responsive to front-line concerns while maintaining control over the improvement process, and share information across all levels of the hospital hierarchy. Teams in successful hospitals did not avoid interdisciplinary conflict, but rather allowed each discipline to contribute to the team from its own perspective. Successful QI teams addressed the concerns of each involved discipline, modified protocols guided by clinical outcomes, and became conduits of information on changes to care processes to both executive managers and front-line staff. PMID- 22042751 TI - The vomeronasal organ of New World monkeys (platyrrhini). AB - Although all platyrrhine primates possess a vomeronasal organ (VNO), few species have been studied in detail. Here, we revisit the microanatomy of the VNO and related features in serially sectioned samples from 41 platyrrhine cadavers (14 species) of mixed age. Procedures to identify terminally differentiated vomeronasal sensory neurons (VSNs) via immunolabeling of olfactory marker protein (OMP) were used on selected specimens. The VNO varies from an elongated epithelial tube (e.g., Ateles fusciceps) to a dorsoventrally expanded sac (e.g., Saguinus spp.). The cartilage that surrounds the VNO is J-shaped or U-shaped in most species, and articulates with a groove on the bony palate. Preliminary results indicate a significant correlation between the length of this groove and length of the VNO neuroepithelium, indicating this feature may serve as a skeletal correlate. The VNO neuroepithelium could be identified in all adult primates except Alouatta, in which poor preservation prevented determination. The VNO of Ateles, described in detail for the first time, had several rows of VSNs and nerves in the surrounding lamina propria. Patterns of OMP-reactivity in the VNO of perinatal platyrrhines indicate that few or no terminally differentiated VSNs are present at birth, thus supporting the hypothesis that some platyrrhines may have delayed maturation of the VNO. From a functional perspective, all platyrrhines studied possess structures required for chemoreception (VSNs, vomeronasal nerves). However, some microanatomical findings, such as limited reactivity to OMP in some species, indicate that some lineages of New World monkeys may have a reduced or vestigial vomeronasal system. PMID- 22042752 TI - Management of deep vein thrombosis and prevention of post-thrombotic syndrome. PMID- 22042753 TI - Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses. AB - OBJECTIVES: To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom. DESIGN: Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) study to a lifetime horizon. SETTING: UK National Health Service. Population Cohorts of 50,000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS(2) (Congestive heart failure, Hypertension, Age >= 75 years, Diabetes mellitus, previous Stroke/transient ischaemic attack) score of 2.1. MAIN OUTCOME MEASURES: Quality adjusted life years (QALYs) gained and incremental cost per QALY of dabigatran compared with warfarin. RESULTS: Compared with warfarin, low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 (95% central range -0.083 to 0.267) and 0.146 (-0.029 to 0.322) QALYs. Positive incremental net benefits resulted for high dose dabigatran in 94% of simulations versus warfarin and in 76% of those versus low dose dabigatran. In the economic analysis, high dose dabigatran dominated the low dose, had an incremental cost effectiveness ratio of L23,082 (?26,700; $35,800) per QALY gained versus warfarin, and was more cost effective in patients with a baseline CHADS(2) score of 3 or above. However, at centres that achieved good control of international normalised ratio, such as those in the UK, dabigatran 150 mg was not cost effective, at L42,386 per QALY gained. CONCLUSIONS: This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin. However, no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified. High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled. PMID- 22042754 TI - A 34 year old man with bilateral anterior uveitis and a rash. PMID- 22042755 TI - Cost of dabigatran for atrial fibrillation. PMID- 22042756 TI - Global health cannot be achieved without efforts to curb population growth. PMID- 22042757 TI - Analysts disagree over whether spending on health has risen or fallen. PMID- 22042758 TI - Effect of 25-hydroxyvitamin D3 and 1 alpha,25 dihydroxyvitamin D3 on differentiation and apoptosis of human osteosarcoma cell lines. AB - Osteosarcoma (OS) is a malignant bone tumor predominantly affecting children and adolescents. OS has a 60% survival rate with current treatments; hence, there is a need to identify novel adjuncts to chemotherapeutic regimens. In this pilot study, we investigated the dose-response to 1alpha,25-dihdroxyvitamin D(3) (1,alpha 25(OH)(2) D(3)) and 25-hydroxyvitamin D(3) (25(OH)D(3)) by human OS cell lines, SaOS-2, and 143B. We hypothesized that 1,alpha 25(OH)(2) D(3) and 25(OH)D(3) would stimulate differentiation and induce apoptosis in OS cells in a dose-dependent manner. Human OS cell lines, SaOS-2, and 143B, were treated with 1,alpha 25(OH)(2)D(3) or 25(OH)D(3) or an ethanol control, respectively, at concentrations ranging from 1 to 1,000 nM. Ki67 (a marker of cellular proliferation) immunocytochemistry revealed no significant changes in the expression of Ki-67 or MIB-1 in 1alpha,25(OH)(2)D(3) or 25(OH)D(3) treated SaOS-2 or 143B cells. Both control and 1alpha,25(OH)(2) D(3) treated SaOS-2 and 143B cells expressed vitamin D receptor (VDR). Markers of osteoblastic differentiation in 143B cells and SaOS-2 cells were induced by both 25(OH)D(3) and 1alpha,25(OH)(2) D, and evident by increases in alkaline phosphatase (ALP) activity, osteocalcin (OCN) mRNA expression, and mineralization of extra-cellular matrix (ECM) by alizarin red staining. An increasing trend in apoptosis in response to 25(OH)D(3), in both SaOS-2 and 143B cells was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining. With 1alpha,25(OH)(2)D(3) treatment, apoptosis was evident at higher concentrations only. These preliminary findings suggest that OS cells express VDR and respond to 25(OH)D(3) and 1alpha,25(OH)(2)D(3) by undergoing differentiation and apoptosis. PMID- 22042759 TI - Near and far space: Understanding the neural mechanisms of spatial attention. AB - Visuospatial neglect is a multicomponent syndrome, and one dissociation reported is between neglect for near (peripersonal) and far (extrapersonal) space. Owing to patient heterogeneity and extensive lesions, it is difficult to determine the precise neural mechanisms underlying this dissociation using clinical methodology. In this study, transcranial magnetic stimulation was used to examine the involvement of three areas in the undamaged brain, while participants completed a conjunction search task in near and far space. The brain areas investigated were right posterior parietal cortex (rPPC), right frontal eye field (rFEF), and right ventral occipital cortex (rVO), each of which has been implicated in visuospatial processing. The results revealed a double dissociation, whereby rPPC was involved for search in near space only, whilst rVO only became necessary when the task was completed in far space. These data provide clear evidence for a dorsal and ventral dissociation between the processing of near and far space, which is compatible with the functional roles previously attributed to the two streams. For example, the involvement of the dorsal stream in near space reflects its role in vision for action, because it is within this spatial location that actions can be performed. The results also revealed that rFEF is involved in the processing of visual search in both near and far space and may contribute to visuospatial attention and/or the control of eye-movements irrespective of spatial frame. We discuss our results with respect to their clear ramifications for clinical diagnosis and neurorehabilitation. PMID- 22042760 TI - Adults' future time perspective predicts engagement in physical activity. AB - OBJECTIVE: Our aim was to examine how the relations among known predictors of physical activity, such as age, sex, and body mass index, interact with future time perspective (FTP) and perceived functional limitation to explain adults' engagement in physical activity. METHOD: Self-report data from 226 adults (range 20-88 years) were collected to examine the hypothesis that a more expansive FTP is associated with engagement in physical activity. RESULTS: Results indicated a good fit of the data to the model chi(2) (4, N = 226) = 7.457, p = .14 and accounted for a moderate amount of variance in adults' physical activity (R(2) = 15.7). Specifically, results indicated that perceived functional limitation (beta = -.140) and FTP (beta = .162) were directly associated with physical activity. Age was indirectly associated with physical activity through its association with perceived functional limitation (beta = -.264) and FTP (beta = .541). DISCUSSION: Results indicate that FTP may play an important role in explaining engagement in health promoting behaviors across the life span. Researchers should consider additional constructs and perhaps adopt socioemotional selectivity theory when explaining adults' engagement in physical activity. PMID- 22042761 TI - Partner discrepancies and age differences in marital quality: distinguishing the ideal, expected, and perceived partner. AB - OBJECTIVES: Previous studies have observed a rebound of marital quality in later adulthood. This study tested whether partner discrepancy was a mediator of the age differences in marital quality. METHOD: The present study assessed partner discrepancies and marital quality in 56 couples, 20-79 years old. Two levels of partner standards (ideal and expected standards) and 2 domains of partner characteristics (personality and support) were examined. RESULTS: Husbands' partner discrepancies, but not wives', were found to mediate the curvilinear age differences in martial quality. DISCUSSION: Consistent with the life-span theory of control, the results suggest that adjusting cognition about the partner is essential to the typically higher marital quality in later adulthood. The results also suggest that the level of comparison standards and the specific domain of partner characteristics should be considered in future studies. PMID- 22042762 TI - Correlates of caregiver burden among family caregivers of older Korean Americans. AB - OBJECTIVES: Despite the rapid growth of older ethnic minority populations, knowledge is limited about informal caregiving among these groups. Our aim was to identify correlates of caregiver burden among family caregivers of older Korean Americans (KAs). METHOD: A cross-sectional survey collected data from 146 KA caregivers. Using a modified stress-appraisal model, we examined background and context characteristics (caregiver sex, relationship to care recipient, college education, English proficiency, time in caregiving role, family support network, friend support network), a primary stressor (care recipient functional dependency), a primary appraisal (caregiving hours), and resources (family agreement, care management self-efficacy, service use self-efficacy) as potential correlates of caregiver burden. Interactions between the primary stressor, primary appraisal, and resources were also tested. RESULTS: Being female and the care recipient's spouse were associated with higher burden. Conversely, a larger family support network, greater family agreement, and greater care management self-efficacy were associated with lower burden. A significant interaction was detected between functional dependency and family agreement; higher levels of family agreement moderated the association between care recipient functional dependency and caregiver burden. DISCUSSION: Interventions to reduce caregiver burden in KA caregivers may be more effective if they include approaches specifically designed to build family support, improve family agreement, and increase caregivers' self-efficacy. PMID- 22042763 TI - Personal and neighborhood resources, future time perspective, and social relations in middle and older adulthood. AB - OBJECTIVES: Aging-related changes in motivation and the availability of resources have been hypothesized to result in social network changes in later life. However, few studies have examined associations of both motivation and resources with different aspects of social network composition in the same analytical context. The present study examined associations of key motivational (future time perspective [FTP]) and resource variables (partner status, physical health, and perceived neighborhood cohesion) with social network size and positive and negative social exchanges. METHOD: A population-based sample of midlife (aged 55 59 years, n = 169) young-old (aged 60-74 years, n = 306) and old-old (aged 75+ years, n = 77) adults completed a questionnaire. RESULTS: Those who were partnered reported larger networks with family, whereas never-married individuals reported larger networks with neighbors. Perceived neighborhood cohesion was related to larger networks with family, neighbors, and friends. Open-ended FTP was associated with larger networks of friends and more frequent positive social exchanges. DISCUSSION: Our results point to FTP and resources having different implications for social engagement across network domains. PMID- 22042764 TI - Comparing the pulmonary embolism severity index and the prognosis in pulmonary embolism scores as risk stratification tools. AB - BACKGROUND: Multiple risk stratification scoring systems exist to forecast outcomes in patients with acute pulmonary embolism (PE). OBJECTIVE: We evaluated the comparative validity of the PE severity index (PESI) and the prognosis in pulmonary embolism (PREP) scores to predict mortality in acute PE. DESIGN: Retrospective observational cohort study. SETTING: Washington Hospital Center, Washington, DC. PATIENTS: Consecutive adults (aged >18 years) diagnosed with acute PE. INTERVENTION: The PESI and PREP scores were calculated. MEASUREMENTS: Raw PESI scores were segregated into risk class (I-V) and then dichotomized into low (I-II) versus high (III-V) risk groups; the raw PREP scores were divided into low (0-7) versus high (>7) risk groups. The primary endpoint was 30-day and 90 day mortality. We determined the negative predictive value and computed the area under the receiver operating characteristics (AUROC) curves to compare the ability of these scoring tools. RESULTS: The cohort consisted of 302 subjects. Thirty-day mortality was 3.0%, and 4.0% died within 90 days. The PESI and the PREP performed similarly (PESI AUROC: 0.858 [95% confidence interval (CI), 0.773 0.943] vs 0.719 [95% CI, 0.563-0.875] for PREP). Segregating these scores into risk categories did not affect their discriminatory power (AUROC: 0.684 [95% CI, 0.559-0.810] for PESI and 0.790 [95% CI, 0.679-0.903] for PREP). The negative predictive value for death of being classified as low risk by the PESI or PREP was 100% and 99%, respectively. CONCLUSIONS: The PREP score performed comparably to the PESI score for identifying PE patients at low risk for short-term and intermediate-term mortality. PMID- 22042765 TI - Partial support for ZNF804A genotype-dependent alterations in prefrontal connectivity. AB - Genome-wide association studies identified the single nucleotide polymorphism rs1344706 in ZNF804A as a common risk-variant for schizophrenia and bipolar disorder. Whereas the molecular function of ZNF804A is yet unclear, recent imaging genetics studies have started to characterize the neural systems architecture linking rs1344706 genotype to psychosis. Carring rs1344706 risk alleles was associated with a decrease in functional connectivity within the dorsolateral prefrontal cortices (DLPFCs) as well as an increase in connectivity between the DLPFC and the hippocampal formation (HF) in the context of a working memory task. The present study aimed at replicating these findings in an independent sample of 94 healthy subjects. Subjects were genotyped for rs1344706 and performed a working memory task during functional magnetic resonance imaging. Results indicate no support for a decrease of functional coupling between the bilateral DLPFCs at higher ZNF804A risk status. However, the current data show the previously described alteration in functional coupling between the right DLPFC and the HFs, albeit with weaker effects. Decoupled by default, the functional connectivity between the right DLPFC and anterior HFs increased with the number of rs1344706 risk alleles. The present data support fronto-hippocampal dysconnectivity as intermediate phenotype linking rs1344706 genotype to psychosis. We discuss the issues in replicating the interhemispheric DLPFC coupling in light of the effect sizes rs1344706 genotype has on brain function, concluding that further independent replication studies are fundamentally needed to ascertain the role of rs1344706 in the functional integration of neural systems. PMID- 22042766 TI - Hospital quality and patient safety competencies: development, description, and recommendations for use. AB - BACKGROUND: Hospitalists are poised to have a tremendous impact on improving the quality of care for hospitalized patients. However, many hospitalists are inadequately prepared to engage in efforts to improve quality, because medical schools and residency programs have not traditionally emphasized healthcare quality and patient safety in their curricula. METHODS: Through a multistep process, the Society of Hospital Medicine (SHM) Quality Improvement Education (QIE) subcommittee developed the Hospital Quality and Patient Safety (HQPS) Competencies to provide a framework for developing and assessing curricula and other professional development experiences. This article describes the development, provides definitions, and makes recommendations on the use of the HQPS Competencies. RESULTS: The 8 areas of competence include: Quality Measurement and Stakeholder Interests, Data Acquisition and Interpretation, Organizational Knowledge and Leadership Skills, Patient Safety Principles, Teamwork and Communication, Quality and Safety Improvement Methods, Health Information Systems, and Patient Centeredness. Reflecting differing levels of hospitalist involvement in healthcare quality, 3 levels of expertise within each area of competence have been established: basic, intermediate, and advanced. Standards for each competency area use carefully selected action verbs to reflect educational goals for hospitalists at each level. CONCLUSIONS: Formal incorporation of the HQPS Competencies into professional development programs, and innovative educational initiatives and curricula, will help provide current hospitalists and the next generations of hospitalists with the needed skills to be successful. PMID- 22042768 TI - Elucidation of the sugar recognition ability of the lectin domain of UDP GalNAc:polypeptide N-acetylgalactosaminyltransferase 3 by using unnatural glycopeptide substrates. AB - Mucin-type glycosylation [alpha-N-acetyl-D-galactosamine (alpha-GalNAc)-O Ser/Thr] on proteins is initiated biosynthetically by 16 homologous isoforms of GalNAc-Ts (uridine diphosphate-GalNAc:polypeptide N acetylgalactosaminyltransferases). All the GalNAc-Ts consist of a catalytic domain and a lectin domain. Previous reports of GalNAc-T assays toward peptides and alpha-GalNAc glycopeptides showed that the lectin domain recognized the sugar on the substrates and affected the reaction; however, the details are not clear. Here, we report a new strategy to give insight on the sugar recognition ability and the function of the GalNAc-T3 lectin domain using chemically synthesized natural-type (alpha-GalNAc-O-Thr) and unnatural-type [beta-GalNAc-O-Thr, alpha Fuc-O-Thr and beta-GlcNAc-O-Thr] MUC5AC glycopeptides. GalNAc-T3 is one of isoforms expressed in various organs, its substrate specificity extensively characterized and its anomalous expression has been identified in several types of cancer (e.g. pancreas and stomach). The glycopeptides used in this study were designed based on a preliminary peptide assay with a sequence derived from the MUC5AC tandem repeat. Through GalNAc-T3 and lectin-inactivated GalNAc-T3, competition assays between the glycopeptide substrates and product analyses (MALDI-TOF MS, RP-HPLC and ETD-MS/MS), we show that the lectin domain strictly recognized GalNAc on the substrate and this specificity controlled the glycosylation pathway. PMID- 22042767 TI - A new glycoengineered insect cell line with an inducibly mammalianized protein N glycosylation pathway. AB - The inability to produce recombinant glycoproteins with authentic N-glycans is a limitation of many heterologous protein expression systems. In the baculovirus insect cell system, this limitation has been addressed by glycoengineering insect cell lines with mammalian genes encoding protein N-glycosylation functions ("glycogenes") under the transcriptional control of constitutive promoters. However, a potential problem with this approach is that the metabolic load imposed by the expression of multiple transgenes could adversely impact the growth and/or stability of glycoengineered insect cell lines. Thus, we created a new transgenic insect cell line (SfSWT-5) with an inducibly mammalianized protein N-glycosylation pathway. Expression of all six glycogenes was induced when uninfected SfSWT-5 cells were cultured in growth medium containing doxycycline. Higher levels of expression and induction were observed when SfSWT-5 cells were cultured with doxycycline and infected with a baculovirus. Interestingly, there were no major differences in the short-term growth properties of SfSWT-5 cells cultured with or without doxycycline. Furthermore, there were no major differences in the phenotypic stability of these cells after continuous culture for over 300 passages with or without doxycycline. Baculovirus-infected Sf9 and SfSWT-5 cells produced about the same amounts of a model recombinant glycoprotein, but only the latter sialylated this product and sialylation was more pronounced when the cells were treated with doxycycline. In summary, this is the first report of a lower eukaryotic system with an inducibly mammalianized protein N-glycosylation pathway and the first to examine how the presumed metabolic load imposed by multiple transgene expression impacts insect cell growth and stability. PMID- 22042769 TI - Element content analysis by WDXRF in pistachios grown under organic and conventional farming regimes for human nutrition and health. AB - In this investigation, the elemental composition of various Antep pistachios (Pistacia vera L.) samples was determined using a sensitive method called wavelength dispersive x-ray fluorescence (WDXRF). A total of 27 elements, such as Al, As, Bi, Ca, Cd, Cu, Fe, Mn, Ni, P, S, Sr, Zn, Cl, Pb, K, Mg, Na, Ba, Rb, Si, Br, Sn, Au, La, Ti and Zr, were determined in pistachios samples (n = 10) grown under organic and conventional farming regimes. The obtained results from each group were analyzed statistically using SPSS statistic program. It was observed that the concentration and peak intensity values of Ca, Fe, Mn, P, Mg, Cl, Na and K elements were higher in the pistachios samples grown under organic farming regime. Similarly, Al was found in higher level in the samples grown under conventional farming regime. As, Bi, Cd, Pb, Ti, La, Sn and Zr contents were measured. Their contents were below the detection limits. Our findings clearly revealed that organic pistachios are likely to have higher nutritional mineral content. The pistachios samples grown under conventional farming regime could contain harmful metals like Al that might damage various systems and/or organs of humans and animals. PMID- 22042770 TI - Occupational genotoxicity among copper smelters. AB - Occupational exposure in a copper smelting industry may produce various adverse health effects including cancer. Despite a number of well-documented studies reporting an increased risk of cancer among copper smelter workers, the data on genotoxic effects in this industry are scarce. In view of the above, an assessment of DNA damage in peripheral blood leukocytes by Comet assay from copper smelter workers was undertaken. Additionally, the proton-induced X-ray emission (PIXE) analysis was assessed to determine the metal content of samples. The study was conducted with all workers from a copper smelter (males; n = 11), and a control group (n = 11) was recruited. The results of our study showed a significant increase (p < 0.001; Mann-Whitney test) in DNA damage in peripheral blood lymphocytes of smelter workers, compared to the controls (p < 0.001; Mann Whitney test). No correlation between DNA damage or metal concentration and age mean or time of exposure was found under study. Our findings indicate that copper smelter workers have increased levels of DNA damage in somatic cells, suggesting a potential health risk for the workers. PIXE results show the presence of copper, iron, and other metals. PMID- 22042771 TI - Treatment with folic acid ameliorated the histopathological alterations caused by propylthiouracil-induced hypothyroid rat testes. AB - Hypothyroidism is an underactive thyroid gland that cannot make enough thyroid hormone to keep the body running normally. Here we studied the histopathological, immunohistochemical, and ultrastructural changes in the hypothyroid rat testes at the postpubertal stage, in addition to the ameliorating role of folic acid in enhancing spermatogenesis, boosting sperm concentration and building up the antioxidant status against the oxidants. A total of 50 male albino rats were equally divided into 5 groups; the first and second groups comprised the control and folic acid groups, respectively; while the third group comprised the hypothyroid group in which rats received 6-n-propyl-2-thiouracil in drinking water for 6 weeks to induce hypothyroidism. The fourth and fifth groups comprised hypothyroid rats treated with folic acid for 4 weeks and dissected after 6 and 10 weeks, respectively. Testes in the hypothyroid rats showed marked morphological and histological changes in the seminiferous tubules with a reduction in sperm count. Our results indicate that hypothyroidism adversely affects spermatogenesis, suggesting that thyroid hormone might play an important role not only in controlling normal testicular development but also in maintaining normal testicular function and spermatogenesis. Further, we suggested an ameliorating role of folic acid in the relief of testicular tissue from changes due to hypothyroidism. However, we found that the best results were found in cases where folic acid was used as an adjuvant therapy for returning to the euthyroid state. PMID- 22042772 TI - Employing volcanic tuff minerals in interior architecture design to reduce microbial contaminants and airborne fungal carcinogens of indoor environments. AB - Indoor volatile organic compounds (VOCs) have posed significant risks to human health since people have both shifted to a life spent, for the most part, indoors. Further, changes in materials used in the construction of buildings, furnishings, and tools either leak or encourage the production of VOCs. Whether these enclosed areas are residences, hospitals or workplaces (specifically composting facilities or closed farm buildings for raising livestock), VOCs can rise to levels that threaten people's health. VOCs can either originate from phenolic and benzene-like compounds in building materials and office furniture or from molds (fungi) growing inside improperly ventilated or sealed buildings. Regardless of the source, exposure to VOCs could lead to significant health concerns from sick-building syndrome, 'leukemia houses,' in-hospital fungemia cases or occupation-associated cancer epidemics due to aflatoxicosis. Innovative 21st-century building materials could offer solutions to these challenges. We propose that volcanic materials, clays and minerals (volcanic tuff, modified clay montmorillonite and mineral clinoptilolite), in their original or chemically modified form, could act like synthetic lungs in building walls, breathing and filtering VOCs, and thus limiting human exposure to disease. PMID- 22042773 TI - MicroRNA-mediated dysregulation of neural developmental genes in HPRT deficiency: clues for Lesch-Nyhan disease? AB - Mutations in the gene encoding the purine biosynthetic enzyme hypoxanthine guanine phosphoribosyltransferase (HPRT) cause the intractable neurodevelopmental Lesch-Nyhan disease (LND) associated with aberrant development of brain dopamine pathways. In the current study, we have identified an increased expression of the microRNA miR181a in HPRT-deficient human dopaminergic SH-SY5Y neuroblastoma cells. Among the genes potentially regulated by miR181a are several known to be required for neural development, including Engrailed1 (En1), Engrailed2 (En2), Lmx1a and Brn2. We demonstrate that these genes are down-regulated in HPRT deficient SH-SY5Y cells and that over-expression of miR181a significantly reduces endogenous expression of these genes and inhibits translation of luciferase plasmids bearing the En1/2 or Lmx1a 3'UTR miRNA-binding elements. Conversely, inhibition of miR181a increases the expression of these genes and enhances translation of luciferase constructs bearing the En1/2 and Lmx1a 3'UTR miRNA binding sequences. We also demonstrate that key neurodevelopmental genes (e.g. Nurr1, Pitx3, Wnt1 and Mash1) known to be functional partners of Lmx1a and Brn2 are also markedly down-regulated in SH-SY5Y cells over-expressing miR181a and in HPRT-deficient cells. Our findings in SH-SY5Y cells demonstrate that HPRT deficiency is accompanied by dysregulation of some of the important pathways that regulate the development of dopaminergic neurons and dopamine pathways and that this defect is associated with and possibly due at least partly to aberrant expression of miR181a. Because aberrant expression of miR181a is not as apparent in HPRT-deficient LND fibroblasts, the relevance of the SH-SY5Y neuroblastoma cells to human disease remains to be proven. Nevertheless, we propose that these pleiotropic neurodevelopment effects of miR181a may play a role in the pathogenesis of LND. PMID- 22042774 TI - Rare missense variants in CHRNB4 are associated with reduced risk of nicotine dependence. AB - Genome-wide association studies have identified common variation in the CHRNA5 CHRNA3-CHRNB4 and CHRNA6-CHRNB3 gene clusters that contribute to nicotine dependence. However, the role of rare variation in risk for nicotine dependence in these nicotinic receptor genes has not been studied. We undertook pooled sequencing of the coding regions and flanking sequence of the CHRNA5, CHRNA3, CHRNB4, CHRNA6 and CHRNB3 genes in African American and European American nicotine-dependent smokers and smokers without symptoms of dependence. Carrier status of individuals harboring rare missense variants at conserved sites in each of these genes was then compared in cases and controls to test for an association with nicotine dependence. Missense variants at conserved residues in CHRNB4 are associated with lower risk for nicotine dependence in African Americans and European Americans (AA P = 0.0025, odds-ratio (OR) = 0.31, 95% confidence interval (CI) = 0.31-0.72; EA P = 0.023, OR = 0.69, 95% CI = 0.50-0.95). Furthermore, these individuals were found to smoke fewer cigarettes per day than non-carriers (AA P = 6.6 * 10(-5), EA P = 0.021). Given the possibility of stochastic differences in rare allele frequencies between groups replication of this association is necessary to confirm these findings. The functional effects of the two CHRNB4 variants contributing most to this association (T375I and T91I) and a missense variant in CHRNA3 (R37H) in strong linkage disequilibrium with T91I were examined in vitro. The minor allele of each polymorphism increased cellular response to nicotine (T375I P = 0.01, T91I P = 0.02, R37H P = 0.003), but the largest effect on in vitro receptor activity was seen in the presence of both CHRNB4 T91I and CHRNA3 R37H (P = 2 * 10(-6)). PMID- 22042775 TI - Banning abortion and contraception infringes women's right to health, UN assembly hears. PMID- 22042776 TI - Watchdog uncovers "a culture of abuse" at Essex hospital. PMID- 22042777 TI - Switzerland needs more GPs if it is to tackle growing burden of chronic disease. PMID- 22042778 TI - Ninety per cent of violent deaths are unrelated to wars. PMID- 22042779 TI - Pharmacists may be allowed to change prescriptions without consulting prescriber. PMID- 22042780 TI - US committee recommends HPV vaccine for boys. PMID- 22042781 TI - Bahraini doctors' salaries are axed as they await retrial for crimes against the state. PMID- 22042782 TI - New NHS commissioning board gets to work. PMID- 22042783 TI - Phase III randomized trial of dose intensive neoadjuvant chemotherapy with or without G-CSF in locally advanced breast cancer: long-term results. AB - OBJECTIVE: To compare the pathologic complete response (pCR) rate of patients treated with 5-fluorouracil (5-FU), doxorubicin, and cyclophosphamide (FAC) versus dose-intense FAC plus G-CSF in the neoadjuvant setting and to compare the delivered dose intensity, disease-free survival (DFS) and overall survival (OS) times, and toxicity between treatment arms in patients with breast cancer. METHODS: Patients were randomized to receive preoperative FAC (5-FU, 500 mg/m(2); doxorubicin, 50 mg/m(2); cyclophosphamide, 500 mg/m(2)) every 21 days for four cycles or dose-intense FAC (5-FU, 600 mg/m(2); doxorubicin, 60 mg/m(2); cyclophosphamide, 1,000 mg/m(2)) plus G-CSF every 18 days for four cycles. RESULTS: Two hundred two patients were randomly assigned. The median follow-up was 7.5 years. Patients randomized to FAC plus G-CSF had a higher pCR rate as well as clinical complete response rate; however, these differences were not statistically different from those with the FAC arm. Patients in the FAC + G-CSF arm had a higher delivered dose intensity of doxorubicin in the neoadjuvant and adjuvant settings than those in the standard FAC arm. DFS and OS times were not significantly different between the two groups. However, the OS and DFS rates were significantly higher for patients who achieved a pCR than for those who did not. Thrombocytopenia, febrile neutropenia, and infection rates were higher in the FAC + G-CSF arm. CONCLUSIONS: A higher delivered dose intensity of doxorubicin with the FAC + G-CSF regimen did not result in a statistically significant higher pCR rate. However, patients who achieved a pCR experienced longer DFS and OS times. PMID- 22042784 TI - Clinical development of VEGF signaling pathway inhibitors in childhood solid tumors. AB - Angiogenesis is a target shared by both adult epithelial cancers and the mesenchymal or embryonal tumors of childhood. Development of antiangiogenic agents for the pediatric population has been complicated by largely theoretical concern for toxicities specific to the growing child and prioritization among the many antiangiogenic agents being developed for adults. This review summarizes the mechanism of action and preclinical data relevant to childhood cancers and early phase clinical trials in childhood solid tumors. Single-agent adverse event profiles in adults and children are reviewed with emphasis on cardiovascular, bone health, and endocrine side effects. In addition, pharmacological factors that may be relevant for prioritizing clinical trials of these agents in children are reviewed. Considerations for further clinical evaluation should include preclinical data, relative potency, efficacy in adults, and the current U.S. Food and Drug Administration approval status. Toxicity profiles of vascular endothelial growth factor (VEGF) signaling pathway inhibitors may be age dependent and ultimately, their utility in the treatment of childhood cancer will require combination with standard cytotoxic drugs or other molecularly targeted agents. In combination studies, toxicity profiles, potential drug interactions, and late effects must be considered. Studies to assess the long-term impact of VEGF signaling pathway inhibitors on cardiovascular, endocrine, and bone health in children with cancer are imperative if these agents are to be administered to growing children and adolescents with newly diagnosed cancers. PMID- 22042785 TI - Acinar cell carcinoma of the pancreas: new genetic and treatment insights into a rare malignancy. AB - BACKGROUND: Acinar cell carcinoma (ACC) of the pancreas is a rare neoplasm, accounting for 1% of all pancreatic neoplasms. There remains a lack of data regarding the use of systemic therapy in this disease. We present a series of 40 consecutive cases of ACC of the pancreas treated at Memorial Sloan-Kettering Cancer Center, with an emphasis on evaluation of activity of new therapeutic agents. METHODS: Patients reviewed at our institution from January 2000 through January 2011 were identified from an institutional database with prior institutional review board approval. Pathology was confirmed in all cases as ACC or a closely related entity. RESULTS: Forty patients were identified; 29 were male (73%). The median age at diagnosis was 65 years (range, 16-87 years). The median overall survival (OS) time for patients with localized, resectable disease was 56.9 months and the OS time for patients with metastatic ACC (n = 18) was 19.6 months. Six patients with metastatic or recurrent ACC had a partial response to chemotherapy and five patients had stable disease for >=6 months on systemic chemotherapy. Clinical observation was made of a patient with ACC and hereditary nonpolyposis colorectal cancer and a patient with ACC and a BRCA1 germline mutation. CONCLUSIONS: ACC is moderately chemoresponsive to agents that have activity in pancreatic adenocarcinoma and colorectal carcinoma. A potential association between germline mutations in DNA mismatch repair genes and ACC warrants further evaluation. PMID- 22042786 TI - Hot flashes: a review of pathophysiology and treatment modalities. AB - Many therapies are being studied for the treatment of hot flashes for individuals with cancer, yet few studies have demonstrated safe and effective clinical benefit for those who suffer from this distressing symptom. The purpose of this paper is to assess the current options for the management of hot flashes, examining key endpoints from recent clinical trials and reviewing future directions. Hot flashes are a common stressful symptom for individuals with cancer, particularly women with a history of breast cancer and men with prostate cancer. Lifestyle modifications are proposed as the first step in the management of less severe hot flashes. Several publications have addressed nonhormonal agents as a treatment option for hot flashes. Newer antidepressant and anticonvulsant agents have been studied and show potential in treating vasomotor symptoms. Although many complementary and alternative therapies, including herbal medications and phytoestrogens, have been studied for the treatment of hot flashes, none are clinically recommended at this time. Additionally, further evidence is needed for supportive exercise such as yoga and relaxation techniques. Acupuncture may warrant further investigation in the reduction and severity of hot flashes in both men and women. Hormonal therapies, including estrogens and progestogens, are the most well-known and efficient agents in alleviating hot flashes; however, the safety of these agents is disputable. PMID- 22042787 TI - Second malignancies among elderly survivors of cancer. AB - The U.S. population is aging, life expectancy is increasing, and cancer is a disease associated with aging. Advances in screening and therapeutics have led to a growing number of cancer survivors who are at risk for the development of secondary malignancies. Although the risks for the development of second malignancies following a first diagnosis of cancer are well described for survivors of childhood malignancies, there are fewer data for malignancies common in older adults. With the aging of the U.S. population, and with improving survival statistics in many adult malignancies, there is an increasing need to identify those second malignancies that might develop in the older adult survivor of cancer. In this paper, we describe the types and rates of second malignancies following cancers commonly seen in older adults and review the literature on these malignancies. Comparisons are made between older and younger adults with regard to the risks for developing treatment-related cancers with different modalities. Recommendations for early detection of second malignancies are summarized, though there remains an unmet need for evidence-based guidelines for screening for second malignancies in the older adult in particular. PMID- 22042788 TI - Survival prediction for terminally ill cancer patients: revision of the palliative prognostic score with incorporation of delirium. AB - PURPOSE: An existing and validated palliative prognostic (PaP) score predicts survival in terminally ill cancer patients based on dyspnea, anorexia, Karnofsky performance status score, clinical prediction of survival, total WBC, and lymphocyte percentage. The PaP score assigns patients to three different risk groups according to a 30-day survival probability--group A, >70%; group B, 30% 70%; group C, <30%. The impact of delirium is known but was not incorporated into the PaP score. MATERIALS AND METHODS: Our aim was to incorporate information on delirium into the PaP score based on a retrospective series of 361 terminally ill cancer patients. We followed the approach of "validation by calibration," proposed by van Houwelingen and later adapted by Miceli for achieving score revision with inclusion of a new variable. The discriminating performance of the scores was estimated using the K statistic. RESULTS: The prognostic contribution of delirium was confirmed as statistically significant (p < .001) and the variable was accordingly incorporated into the PaP score (D-PaP score). Following this revision, 30-day survival estimates in groups A, B, and C were 83%, 50%, and 9% for the D-PaP score and 87%, 51%, and 16% for the PaP score, respectively. The overall performance of the D-PaP score was better than that of the PaP score. CONCLUSION: The revision of the PaP score was carried out by modifying the cutoff values used for prognostic grouping without, however, affecting the partial scores of the original tool. The performance of the D-PaP score was better than that of the PaP score and its key feature of simplicity was maintained. PMID- 22042789 TI - Assessing acid retention. PMID- 22042791 TI - Feeling different: the experience of living with fetal alcohol spectrum disorder. AB - BACKGROUND: In Canada the incidences of Fetal Alcohol Spectrum Disorder (FASD) is estimated to be in 1 in 100 live births caused by prenatal exposure to alcohol, the disorder is the leading cause of developmental and cognitive disabilities among Canadian children and its effects are life lasting. No research has attempted to describe the experience of living with FASD from the perspective of Canadian children. PURPOSE: The main purpose of this study was to describe the children's experience of living with FASD. METHODS: A qualitative method was used to examine the children's experiences. Twenty-two (22) children, aged 6 to 18 years, living in urban and rural communities across Canada participated in an unstructured in-depth interview. Data was analysed using Colaizzi's qualitative method. RESULTS: For all children in this study, living day-to-day with FASD meant feeling different. Within this construct knowing the disability; feeling alone-feeling supported, and overcoming the disability were dominant themes which emerged. CONCLUSION: Implications for practice and research have been described. KEYWORDS: Fetal Alcohol Spectrum Disorder, children's experience, qualitative research. PMID- 22042792 TI - Dual IGF-1R/InsR inhibitor BMS-754807 synergizes with hormonal agents in treatment of estrogen-dependent breast cancer. AB - Insulin-like growth factor (IGF) signaling has been implicated in the resistance to hormonal therapy in breast cancer. Using a model of postmenopausal, estrogen dependent breast cancer, we investigated the antitumor effects of the dual IGF 1R/InsR tyrosine kinase inhibitor BMS-754807 alone and in combination with letrozole or tamoxifen. BMS-754807 exhibited antiproliferative effects in vitro that synergized strongly in combination with letrozole or 4-hydroxytamoxifen and fulvestrant. Similarly, combined treatment of BMS-754807 with either tamoxifen or letrozole in vivo elicited tumor regressions not achieved by single-agent therapy. Notably, hormonal therapy enhanced the inhibition of IGF-1R/InsR without major side effects in animals. Microarray expression analysis revealed downregulation of cell-cycle control and survival pathways and upregulation of erbB in response to BMS-754807 plus hormonal therapy, particularly tamoxifen. Overall, these results offer a preclinical proof-of-concept for BMS-754807 as an antitumor agent in combination with hormonal therapies in hormone-sensitive breast cancer. Cooperative cell-cycle arrest, decreased proliferation, and enhanced promotion of apoptosis may contribute to antitumor effects to be gauged in future clinical investigations justified by our findings. PMID- 22042794 TI - Angiopoietin-like protein 2 is an important facilitator of inflammatory carcinogenesis and metastasis. AB - Chronic inflammation plays important roles at different stages of cancer development, including carcinogenesis, tumor invasion, and metastasis, but molecular mechanisms linking inflammation to cancer development have not been fully clarified. Here, we report that expression of angiopoietin-like protein 2 (Angptl2), recently identified as a chronic inflammation mediator, is highly correlated with the frequency of carcinogenesis in a chemically induced skin squamous cell carcinoma (SCC) mouse model. Furthermore, Angptl2 expression in SCC is highly correlated with the frequency of tumor cell metastasis to distant secondary organs and lymph nodes. When SCC was induced in transgenic mice expressing Angptl2 in skin epithelial cells, epithelial-to-mesenchymal transitions in SCC as well as tumor angiogenesis and lymphangiogenesis were significantly increased, resulting in increased tumor cell metastasis and shortened survival compared with wild-type mice. Conversely, in a chemically induced SCC mouse model, carcinogenesis and metastasis were markedly attenuated in Angptl2 knockout mice, resulting in extended survival compared with wild-type mice. Overall, we propose that Angptl2 contributes to increased carcinogenesis and metastasis and represents a novel target to antagonize these pathologies. PMID- 22042793 TI - In vivo magnetic resonance imaging of the estrogen receptor in an orthotopic model of human breast cancer. AB - Histologic overexpression of the estrogen receptor alpha (ER) is a well established prognostic marker in breast cancer. Noninvasive imaging techniques that could detect ER overexpression would be useful in a variety of settings where patients' biopsies are problematic to obtain. This study focused on developing, by in vivo MRI, strategies to measure the level of ER expression in an orthotopic mouse model of human breast cancer. Specifically, novel ER-targeted contrast agents based on pyridine-tetra-acetate-Gd(III) chelate (PTA-Gd) conjugated to 17beta-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd) were examined in ER-positive or ER-negative tumors. Detection of specific interactions of EPTA Gd with ER were documented that could differentiate ER-positive and ER-negative tumors. In vivo competition experiments confirmed that the enhanced detection capability of EPTA-Gd was based specifically on ER targeting. In contrast, PTA-Gd acted as an extracellular probe that enhanced ER detection similarly in either tumor type, confirming a similar vascular perfusion efficiency in ER-positive and ER-negative tumors in the model. Finally, TPTA-Gd accumulated selectively in muscle and could not preferentially identify ER-positive tumors. Together, these results define a novel MRI probe that can permit selective noninvasive imaging of ER-positive tumors in vivo. PMID- 22042795 TI - Care and outcomes in patients with ischemic stroke with and without preexisting dementia. AB - OBJECTIVE: To describe clinical characteristics and evaluate processes of care and outcomes at discharge in patients with ischemic stroke with and without preexisting dementia. METHODS: Retrospective cohort study using the Registry of the Canadian Stroke Network including patients presenting with an acute ischemic stroke between 2003 and 2008. Preexisting dementia was defined as any type of dementia that was present prior to the index stroke case. Palliative patients were excluded. Demographic information, clinical presentation, selected process measures (e.g., thrombolysis, admission to stroke unit, carotid imaging, stroke prevention), pneumonia, death, disability, and disposition at discharge were analyzed. RESULTS: Among 9,304 eligible patients with an acute ischemic stroke, 702 (9.1%) had a history of dementia. Patients with dementia were older (mean age 81 vs 70 years; p < 0.001), had more severe strokes (Canadian Neurological Scale score <4, 20.7% vs 10.5%; p < 0.001), and were more likely to have atrial fibrillation (22.8% vs 15.3%; p < 0.001) than those without dementia. Patients with dementia were slightly less likely to be admitted to a stroke unit (63% vs 67.6%; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70-0.96) or to receive thrombolysis (10.5% vs 15.7%; OR 0.63, 95% CI 0.49-0.81). There were no differences in other performance measures. Patients with preexisting dementia had higher disability at discharge (OR 3.20, 95% CI 2.64-3.87) and were less likely to be discharged to their prestroke place of residence (24% vs 45%; p < 0.001). CONCLUSIONS: In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system. PMID- 22042797 TI - Subspecialization in neurology: the role of the United Council for Neurologic Subspecialties. PMID- 22042798 TI - Suppression of extrapyramidal side effects of doxepin by thalamic deep brain stimulation for Tourette syndrome. PMID- 22042799 TI - Comment on "Chronic cerebrospinal venous insufficiency: have we found the cause and cure of MS?". PMID- 22042800 TI - Comment on "Upholding professionalism: the disciplinary process of the American Academy of Neurology". PMID- 22042801 TI - Teaching NeuroImages: neuroferritinopathy. PMID- 22042802 TI - Teaching NeuroImages: platybasia and basilar invagination in osteogenesis imperfecta. PMID- 22042803 TI - Teaching NeuroImages: cochleitis: a rare cause of acute deafness in a patient with HCV. PMID- 22042804 TI - Social-Event-Driven Camera Control for Multicharacter Animations. AB - In a virtual world, a group of virtual characters can interact with each other, and these characters may leave a group to join another. The interaction among individuals and groups often produces interesting events in a sequence of animation. The goal of this paper is to discover social events involving mutual interactions or group activities in multicharacter animations and automatically plan a smooth camera motion to view interesting events suggested by our system or relevant events specified by a user. Inspired by sociology studies, we borrow the knowledge in Proxemics, social force, and social network analysis to model the dynamic relation among social events and the relation among the participants within each event. By analyzing the variation of relation strength among participants and spatiotemporal correlation among events, we discover salient social events in a motion clip and generate an overview video of these events with smooth camera motion using a simulated annealing optimization method. We tested our approach on different motions performed by multiple characters. Our user study shows that our results are preferred in 66.19 percent of the comparisons with those by the camera control approach without event analysis and are comparable (51.79 percent) to professional results by an artist. PMID- 22042805 TI - Direct Feature Visualization Using Morse-Smale Complexes. AB - In this paper, we characterize the range of features that can be extracted from an Morse-Smale complex and describe a unified query language to extract them. We provide a visual dictionary to guide users when defining features in terms of these queries. We demonstrate our topology-rich visualization pipeline in a tool that interactively queries the MS complex to extract features at multiple resolutions, assigns rendering attributes, and combines traditional volume visualization with the extracted features. The flexibility and power of this approach is illustrated with examples showing novel features. PMID- 22042806 TI - Acute and subacute effects of the great East Japan earthquake on home blood pressure values. PMID- 22042807 TI - Resistant hypertension or resistant prescribing? PMID- 22042808 TI - Renal denervation for sleep apnea and resistant hypertension: alternative or complementary to effective continuous positive airway pressure treatment? PMID- 22042809 TI - Description of antihypertensive use in patients with resistant hypertension prescribed four or more agents. AB - Data describing the use of recommended antihypertensive agents in the resistant hypertension population are limited. Treatment recommendations for resistant hypertension include maximizing diuretic therapy by using chlorthalidone and/or adding an aldosterone antagonist. Additional recommendations include combining antihypertensive agents from different drug classes. This retrospective cohort study describes antihypertensive use in patients with resistant hypertension defined as the concurrent use of >=4 antihypertensive agents. Claims data from the Medstat MarketScan Commercial Claims and Encounter database were used to identify patients with resistant hypertension based on International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes and National Drug Codes between May 1, 2008 and June 30, 2009. Of the 5 442 410 patients with hypertension in the database, 140 126 met study criteria. The most frequently prescribed antihypertensive classes were angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (96.2%), diuretics (93.2%), calcium channel blockers (83.6%), and beta-blockers (80.0%). Only 3.0% and 5.9% of patients were on chlorthalidone or an aldosterone antagonist, respectively. A total of 15.6% of patients were treated with angiotensin-converting enzyme inhibitor plus angiotensin receptor blocker. Our findings demonstrate that frequently prescribed antihypertensive agents for the treatment of resistant hypertension included guideline-recommended first-line agents. However, evidence-based and recommended agents, such as chlorthalidone and aldosterone antagonists, were underused. Moreover, minimally efficacious combinations, such as an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker, were prescribed at higher rates than evidence-based and recommended agents. PMID- 22042811 TI - Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs. AB - The kidney has long been invoked in the etiology of essential hypertension. This could involve alterations in expression of specific genes and microRNAs (miRNAs). The aim of the present study was to identify, at the transcriptome-wide level, mRNAs and miRNAs that were differentially expressed between kidneys of 15 untreated hypertensive and 7 normotensive white male subjects of white European ancestry. By microarray technology we found 14 genes and 11 miRNAs that were differentially expressed in the medulla. We then selected and confirmed by real time quantitative PCR expression differences for NR4A1, NR4A2, NR4A3, PER1, and SIK1 mRNAs and for the miRNAs hsa-miR-638 and hsa-let-7c. Luciferase reporter gene experiments in human kidney (HEK293) cells confirmed the predicted binding of hsa-let-7c to the 3' untranslated region of NR4A2 mRNA. In the renal cortex we found differential expression of 46 genes and 13 miRNAs. We then confirmed expression differences for AIFM1, AMBP, APOE, CD36, EFNB1, NDUFAF1, PRDX5, REN, RENBP, SLC13A1, STX4, and TNNT2 mRNAs and for miRNAs hsa-miR-21, hsa-miR-126, hsa miR-181a, hsa-miR-196a, hsa-miR-451, hsa-miR-638, and hsa-miR-663. Functional experiments in HEK293 cells demonstrated that hsa-miR-663 can bind to the REN and APOE 3' untranslated regions and can regulate REN and APOE mRNA levels, whereas hsa-miR-181a regulated REN and AIFM1 mRNA. Our data demonstrated for the first time that miRNAs can regulate renin expression. The observed downregulation of 2 miRNAs in hypertension could explain the elevation in intrarenal renin mRNA. Renin, CD36, and other mRNAs, as well as miRNAs and associated pathways identified in the present study, provide novel insights into hypertension etiology. PMID- 22042812 TI - Blood oxygen level-dependent magnetic resonance imaging identifies cortical hypoxia in severe renovascular disease. AB - Atherosclerotic renal artery stenosis has a range of manifestations depending on the severity of vascular occlusion. The aim of this study was to examine whether exceeding the limits of adaptation to reduced blood flow ultimately leads to tissue hypoxia, as determined by blood oxygen level dependent MRI. We compared 3 groups of hypertensive patients, 24 with essential hypertension, 13 with "moderate" (Doppler velocities 200-384 cm/s), and 17 with "severe" atherosclerotic renal artery stenosis (ARAS; velocities >384 cm/s and loss of functional renal tissue). Cortical and medullary blood flows and volumes were determined by multidetector computed tomography. Poststenotic kidney size and blood flow were reduced with ARAS, and tissue perfusion fell in the most severe lesions. Tissue medullary deoxyhemoglobin, as reflected by R2* values, was higher as compared with the cortex for all of the groups and did not differ between subjects with renal artery lesions and essential hypertension. By contrast, cortical R2* levels were elevated for severe ARAS (21.6+/-9.4 per second) as compared with either essential hypertension (17.8+/-2.3 per second; P<0.01) or moderate ARAS (15.7+/-2.1 per second; P<0.01). Changes in medullary R2* after furosemide administration tended to be blunted in severe ARAS as compared with unaffected (contralateral) kidneys. These results demonstrate that severe vascular occlusion overwhelms the capacity of the kidney to adapt to reduced blood flow, manifest as overt cortical hypoxia as measured by blood oxygen level dependent MRI. The level of cortical hypoxia is out of proportion to the medulla and may provide a marker to identify irreversible parenchymal injury. PMID- 22042813 TI - Pregnancy upregulates large-conductance Ca(2+)-activated K(+) channel activity and attenuates myogenic tone in uterine arteries. AB - Uterine vascular tone significantly decreases whereas uterine blood flow dramatically increases during pregnancy. However, the complete molecular mechanisms remain elusive. We hypothesized that increased Ca(2+)-activated K(+) (BK(Ca)) channel activity contributes to the decreased myogenic tone of uterine arteries in pregnancy. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Electrophysiological studies revealed a greater whole-cell K(+) current density in pregnant compared with nonpregnant uterine arteries. Tetraethylammonium and iberiotoxin inhibited K(+) currents to the same extent in uterine arterial myocytes. The BK(Ca) channel current density was significantly increased in pregnant uterine arteries. In accordance, tetraethylammonium significantly increased pressure-induced myogenic tone in pregnant uterine arteries and abolished the difference in myogenic responses between pregnant and nonpregnant uterine arteries. Activation of protein kinase C produced a similar effect to tetraethylammonium by inhibiting BK(Ca) channel activity and increasing myogenic tone in pregnant uterine arteries. Chronic treatment of nonpregnant uterine arteries with physiologically relevant concentrations of 17beta-estradiol and progesterone caused a significant increase in the BK(Ca) channel current density. Western blot analyses demonstrated a significant increase of the beta1, but not alpha, subunit of BK(Ca) channels in pregnant uterine arteries. In accordance, steroid treatment of nonpregnant uterine arteries resulted in an upregulation of the beta1, but not alpha, subunit expression. The results indicate that the steroid hormone-mediated upregulation of the beta1 subunit and BK(Ca) channel activity may play a key role in attenuating myogenic tone of the uterine artery in pregnancy. PMID- 22042814 TI - Body mass index-mortality paradox in hemodialysis: can it be explained by blood pressure? AB - Unlike the general population, among hemodialysis patients body mass index (BMI) is related to blood pressure (BP) and mortality inversely. To explore the reasons for this risk-factor paradox, the cross-sectional association of obesity with the following factors was examined: the prevalence of hypertension, its control, and echocardiographic left ventricular mass index (LVMI). Longitudinal follow-up explored the relationship of BMI with all-cause mortality. Furthermore, it explored whether poorer survival in leaner individuals was related to either high BP or greater LVMI. Among 368 hemodialysis patients, both the prevalence of hypertension and its poor control were inversely related to BMI. BMI was also inversely associated with evidence of excess extracellular fluid volume, but adjustment for this variable did not completely remove the inverse relationship between BP and BMI. Over 1122 patient-years of cumulative follow-up (median: 2.7 years), 119 patients (32%) died. In the first 2 years of follow-up, the mortality hazard for the lowest BMI group was increased; thereafter, the survival curves were similar. Adjusting for several risk factors including BP and LVMI did not remove the inverse relationship of BMI with mortality. In conclusion, leaner patients on dialysis have a higher prevalence of hypertension, poorer control of hypertension, more LVMI, and greater evidence of extracellular fluid volume excess. However, volume explains the greater prevalence or poorer control of hypertension only partially. Leaner patients have an accelerated mortality rate in the first 2 years; this is not completely explained by BP, LVMI, or other cardiovascular or dialysis-specific risk factors. PMID- 22042815 TI - Body mass index-mortality paradox in hemodialysis patients: blood pressure, blood volume, and nutritional status. PMID- 22042816 TI - Adolescents and HIV infection: the pediatrician's role in promoting routine testing. AB - Pediatricians can play a key role in preventing and controlling HIV infection by promoting risk-reduction counseling and offering routine HIV testing to adolescent and young adult patients. Most sexually active youth do not feel that they are at risk of contracting HIV and have never been tested. Obtaining a sexual history and creating an atmosphere that promotes nonjudgmental risk counseling is a key component of the adolescent visit. In light of increasing numbers of people with HIV/AIDS and missed opportunities for HIV testing, the Centers for Disease Control and Prevention recommends universal and routine HIV testing for all patients seen in health care settings who are 13 to 64 years of age. There are advances in diagnostics and treatment that help support this recommendation. This policy statement reviews the epidemiologic data and recommends that routine screening be offered to all adolescents at least once by 16 to 18 years of age in health care settings when the prevalence of HIV in the patient population is more than 0.1%. In areas of lower community HIV prevalence, routine HIV testing is encouraged for all sexually active adolescents and those with other risk factors for HIV. This statement addresses many of the real and perceived barriers that pediatricians face in promoting routine HIV testing for their patients. PMID- 22042817 TI - Providing a primary care medical home for children and youth with cerebral palsy. AB - All primary care providers will care for children with cerebral palsy in their practice. In addition to well-child and acute illness care, the role of the medical home in the management of these children includes diagnosis, planning for interventions, authorizing treatments, and follow-up. Optimizing health and well being for children with cerebral palsy and their families entails family-centered care provided in the medical home; comanagement is the most common model. This report reviews the aspects of care specific to cerebral palsy that a medical home should provide beyond the routine health care needed by all children. PMID- 22042818 TI - Substance use screening, brief intervention, and referral to treatment for pediatricians. AB - As a component of comprehensive pediatric care, adolescents should receive appropriate guidance regarding substance use during routine clinical care. This statement addresses practitioner challenges posed by the spectrum of pediatric substance use and presents an algorithm-based approach to augment the pediatrician's confidence and abilities related to substance use screening, brief intervention, and referral to treatment in the primary care setting. Adolescents with addictions should be managed collaboratively (or comanaged) with child and adolescent mental health or addiction specialists. This statement reviews recommended referral guidelines that are based on established patient-treatment matching criteria and the risk level for substance abuse. PMID- 22042819 TI - Antagonistic action of strigolactone and cytokinin in bud outgrowth control. AB - Cytokinin (CK) has long been implicated as a promoter of bud outgrowth in plants, but exactly how this is achieved in coordination with other plant hormones is unclear. The recent discovery of strigolactones (SLs) as the long-sought branch inhibiting hormone allowed us to test how CK and SL coordinately regulate bud outgrowth in pea (Pisum sativum). We found that SL-deficient plants are more sensitive to stimulation of bud growth by low concentrations of locally applied CK than wild-type plants. Furthermore, in contrast with SL mutant plants, buds of wild-type plants are almost completely resistant to stimulation by CK supplied to the vasculature. Regardless of whether the exogenous hormones were supplied locally or to the xylem stream, SL and CK acted antagonistically on bud outgrowth. These data suggest that SLs do not affect the delivery of CK to axillary buds and vice versa. Rather, these data combined with dose-response experiments suggest that SLs and CK can act directly in buds to control their outgrowth. These hormones may converge at a common point in the bud outgrowth regulatory pathway. The expression of pea BRANCHED1, a TCP transcription factor expressed strongly in buds and thought to act downstream of SLs in shoot branching, is regulated by CK and SL without a requirement for protein synthesis and in a manner that correlates with observed bud growth responses. PMID- 22042822 TI - Vitreoschisis in diabetic macular edema. PMID- 22042827 TI - Plasminogen receptor S100A10 is essential for the migration of tumor-promoting macrophages into tumor sites. AB - Macrophages are critical drivers of tumor growth, invasion, and metastasis. Movement of macrophages into tumors requires the activity of cell surface proteases such as plasmin. In this study, we offer genetic evidence that plasminogen receptor S100A10 is essential for recruitment of macrophages to the tumor site. Growth of murine Lewis lung carcinomas or T241 fibrosarcomas was dramatically reduced in S100A10-deficient mice compared with wild-type mice. The tumor growth deficit corresponded with a decrease in macrophage density that could be rescued by intraperitoneal injection of wild-type but not S100A10 deficient macrophages. Notably, macrophages of either genotype could rescue tumor growth if they were injected into the tumor itself, establishing that S100A10 was required specifically for the migratory capability needed for tumor homing. Conversely, selective depletion of macrophages from wild-type mice phenocopied the tumor growth deficit seen in S100A10-deficient mice. Together, our findings show that S100A10 is essential and sufficient for macrophage migration to tumor sites, and they define a novel rate-limiting step in tumor progression. PMID- 22042829 TI - Things are not always what they appear to be. PMID- 22042831 TI - Fatal Prototheca wickerhamii bloodstream infection in a cardiac allograft recipient. PMID- 22042830 TI - Serial quantitative PCR assay for detection, species discrimination, and quantification of Leishmania spp. in human samples. AB - The Leishmania species cause a variety of human disease syndromes. Methods for diagnosis and species differentiation are insensitive and many require invasive sampling. Although quantitative PCR (qPCR) methods are reported for leishmania detection, no systematic method to quantify parasites and determine the species in clinical specimens is established. We developed a serial qPCR strategy to identify and rapidly differentiate Leishmania species and quantify parasites in clinical or environmental specimens. SYBR green qPCR is mainly employed, with corresponding TaqMan assays for validation. The screening primers recognize kinetoplast minicircle DNA of all Leishmania species. Species identification employs further qPCR set(s) individualized for geographic regions, combining species-discriminating probes with melt curve analysis. The assay was sufficient to detect Leishmania parasites, make species determinations, and quantify Leishmania spp. in sera, cutaneous biopsy specimens, or cultured isolates from subjects from Bangladesh or Brazil with different forms of leishmaniasis. The multicopy kinetoplast DNA (kDNA) probes were the most sensitive and useful for quantification based on promastigote standard curves. To test their validity for quantification, kDNA copy numbers were compared between Leishmania species, isolates, and life stages using qPCR. Maxicircle and minicircle copy numbers differed up to 6-fold between Leishmania species, but the differences were smaller between strains of the same species. Amastigote and promastigote leishmania life stages retained similar numbers of kDNA maxi- or minicircles. Thus, serial qPCR is useful for leishmania detection and species determination and for absolute quantification when compared to a standard curve from the same Leishmania species. PMID- 22042833 TI - Mycobacterial interspersed repetitive-unit locus PCR amplification and Beijing strains of Mycobacterium tuberculosis. PMID- 22042836 TI - Potential effects of the APOE epsilon2 allele and of family history of Alzheimer's disease on brain amyloid-beta in normal elderly. PMID- 22042837 TI - High T(c) electron doped Ca10(Pt3As8)(Fe2As2)5 and Ca10(Pt4As8)(Fe2As2)5 superconductors with skutterudite intermediary layers. AB - It has been argued that the very high transition temperatures of the highest T(c) cuprate superconductors are facilitated by enhanced CuO(2) plane coupling through heavy metal oxide intermediary layers. Whether enhanced coupling through intermediary layers can also influence T(c) in the new high T(c) iron arsenide superconductors has never been tested due the lack of appropriate systems for study. Here we report the crystal structures and properties of two iron arsenide superconductors, Ca(10)(Pt(3)As(8))(Fe(2)As(2))(5) (the "10-3-8 phase") and Ca(10)(Pt(4)As(8))(Fe(2)As(2))(5) (the "10-4-8 phase"). Based on -Ca-(Pt(n)As(8)) Ca-Fe(2)As(2)- layer stacking, these are very similar compounds for which the most important differences lie in the structural and electronic characteristics of the intermediary platinum arsenide layers. Electron doping through partial substitution of Pt for Fe in the FeAs layers leads to T(c) of 11 K in the 10-3-8 phase and 26 K in the 10-4-8 phase. The often-cited empirical rule in the arsenide superconductor literature relating T(c) to As-Fe-As bond angles does not explain the observed differences in T(c) of the two phases; rather, comparison suggests the presence of stronger FeAs interlayer coupling in the 10-4-8 phase arising from the two-channel interlayer interactions and the metallic nature of its intermediary Pt(4)As(8) layer. The interlayer coupling is thus revealed as important in enhancing T(c) in the iron pnictide superconductors. PMID- 22042838 TI - Bayesian modeling to unmask and predict influenza A/H1N1pdm dynamics in London. AB - The tracking and projection of emerging epidemics is hindered by the disconnect between apparent epidemic dynamics, discernible from noisy and incomplete surveillance data, and the underlying, imperfectly observed, system. Behavior changes compound this, altering both true dynamics and reporting patterns, particularly for diseases with nonspecific symptoms, such as influenza. We disentangle these effects to unravel the hidden dynamics of the 2009 influenza A/H1N1pdm pandemic in London, where surveillance suggests an unusual dominant peak in the summer. We embed an age-structured model into a bayesian synthesis of multiple evidence sources to reveal substantial changes in contact patterns and health-seeking behavior throughout the epidemic, uncovering two similar infection waves, despite large differences in the reported levels of disease. We show how this approach, which allows for real-time learning about model parameters as the epidemic progresses, is also able to provide a sequence of nested projections that are capable of accurately reflecting the epidemic evolution. PMID- 22042839 TI - Hyperpolarized 13C dehydroascorbate as an endogenous redox sensor for in vivo metabolic imaging. AB - Reduction and oxidation (redox) chemistry is involved in both normal and abnormal cellular function, in processes as diverse as circadian rhythms and neurotransmission. Intracellular redox is maintained by coupled reactions involving NADPH, glutathione (GSH), and vitamin C, as well as their corresponding oxidized counterparts. In addition to functioning as enzyme cofactors, these reducing agents have a critical role in dealing with reactive oxygen species (ROS), the toxic products of oxidative metabolism seen as culprits in aging, neurodegenerative disease, and ischemia/ reperfusion injury. Despite this strong relationship between redox and human disease, methods to interrogate a redox pair in vivo are limited. Here we report the development of [1-(13)C] dehydroascorbate [DHA], the oxidized form of Vitamin C, as an endogenous redox sensor for in vivo imaging using hyperpolarized (13)C spectroscopy. In murine models, hyperpolarized [1-(13)C] DHA was rapidly converted to [1-(13)C] vitamin C within the liver, kidneys, and brain, as well as within tumor in a transgenic prostate cancer mouse. This result is consistent with what has been previously described for the DHA/Vitamin C redox pair, and points to a role for hyperpolarized [1-(13)C] DHA in characterizing the concentrations of key intracellular reducing agents, including GSH. More broadly, these findings suggest a prognostic role for this new redox sensor in determining vulnerability of both normal and abnormal tissues to ROS. PMID- 22042840 TI - In vitro reconstitution and steady-state analysis of the fatty acid synthase from Escherichia coli. AB - Microbial fatty acid derivatives are emerging as promising alternatives to fossil fuel derived transportation fuels. Among bacterial fatty acid synthases (FAS), the Escherichia coli FAS is perhaps the most well studied, but little is known about its steady-state kinetic behavior. Here we describe the reconstitution of E. coli FAS using purified protein components and report detailed kinetic analysis of this reconstituted system. When all ketosynthases are present at 1 MUM, the maximum rate of free fatty acid synthesis of the FAS exceeded 100 MUM/ min. The steady-state turnover frequency was not significantly inhibited at high concentrations of any substrate or cofactor. FAS activity was saturated with respect to most individual protein components when their concentrations exceeded 1 MUM. The exceptions were FabI and FabZ, which increased FAS activity up to concentrations of 10 MUM; FabH and FabF, which decreased FAS activity at concentrations higher than 1 MUM; and holo-ACP and TesA, which gave maximum FAS activity at 30 MUM concentrations. Analysis of the S36T mutant of the ACP revealed that the unusual dependence of FAS activity on holo-ACP concentration was due, at least in part, to the acyl-phosphopantetheine moiety. MALDI-TOF mass spectrometry analysis of the reaction mixture further revealed medium and long chain fatty acyl-ACP intermediates as predominant ACP species. We speculate that one or more of such intermediates are key allosteric regulators of FAS turnover. Our findings provide a new basis for assessing the scope and limitations of using E. coli as a biocatalyst for the production of diesel-like fuels. PMID- 22042841 TI - Prototypical model for tensional wrinkling in thin sheets. AB - The buckling and wrinkling of thin films has recently seen a surge of interest among physicists, biologists, mathematicians, and engineers. This activity has been triggered by the growing interest in developing technologies at ever decreasing scales and the resulting necessity to control the mechanics of tiny structures, as well as by the realization that morphogenetic processes, such as the tissue-shaping instabilities occurring in animal epithelia or plant leaves, often emerge from mechanical instabilities of cell sheets. Although the most basic buckling instability of uniaxially compressed plates was understood by Euler more than two centuries ago, recent experiments on nanometrically thin (ultrathin) films have shown significant deviations from predictions of standard buckling theory. Motivated by this puzzle, we introduce here a theoretical model that allows for a systematic analysis of wrinkling in sheets far from their instability threshold. We focus on the simplest extension of Euler buckling that exhibits wrinkles of finite length--a sheet under axisymmetric tensile loads. The first study of this geometry, which is attributed to Lame, allows us to construct a phase diagram that demonstrates the dramatic variation of wrinkling patterns from near-threshold to far-from-threshold conditions. Theoretical arguments and comparison to experiments show that the thinner the sheet is, the smaller is the compressive load above which the far-from-threshold regime emerges. This observation emphasizes the relevance of our analysis for nanomechanics applications. PMID- 22042842 TI - Cytoplasmic activation-induced cytidine deaminase (AID) exists in stoichiometric complex with translation elongation factor 1alpha (eEF1A). AB - Activation-induced cytidine deaminase (AID) is a B lymphocyte-specific DNA deaminase that acts on the Ig loci to trigger antibody gene diversification. Most AID, however, is retained in the cytoplasm and its nuclear abundance is carefully regulated because off-target action of AID leads to cancer. The nature of the cytosolic AID complex and the mechanisms regulating its release from the cytoplasm and import into the nucleus remain unknown. Here, we show that cytosolic AID in DT40 B cells is part of an 11S complex and, using an endogenously tagged AID protein to avoid overexpression artifacts, that it is bound in good stoichiometry to the translation elongation factor 1 alpha (eEF1A). The AID/eEF1A interaction is recapitulated in transfected cells and depends on the C-terminal domain of eEF1A (which is not responsible for GTP or tRNA binding). The eEF1A interaction is destroyed by mutations in AID that affect its cytosolic retention. These results suggest that eEF1A is a cytosolic retention factor for AID and extend on the multiple moonlighting functions of eEF1A. PMID- 22042843 TI - Marriage exchanges, seed exchanges, and the dynamics of manioc diversity. AB - The conservation of crop genetic resources requires understanding the different variables-cultural, social, and economic-that impinge on crop diversity. In small scale farming systems, seed exchanges represent a key mechanism in the dynamics of crop genetic diversity, and analyzing the rules that structure social networks of seed exchange between farmer communities can help decipher patterns of crop genetic diversity. Using a combination of ethnobotanical and molecular genetic approaches, we investigated the relationships between regional patterns of manioc genetic diversity in Gabon and local networks of seed exchange. Spatially explicit Bayesian clustering methods showed that geographical discontinuities of manioc genetic diversity mirror major ethnolinguistic boundaries, with a southern matrilineal domain characterized by high levels of varietal diversity and a northern patrilineal domain characterized by low varietal diversity. Borrowing concepts from anthropology--kinship, bridewealth, and filiation--we analyzed the relationships between marriage exchanges and seed exchange networks in patrilineal and matrilineal societies. We demonstrate that, by defining marriage prohibitions, kinship systems structure social networks of exchange between farmer communities and influence the movement of seeds in metapopulations, shaping crop diversity at local and regional levels. PMID- 22042844 TI - Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D beta lactamase OXA-10 by rational protein design. AB - Class D beta-lactamases with carbapenemase activity are emerging as carbapenem resistance determinants in gram-negative bacterial pathogens, mostly Acinetobacter baumannii and Klebsiella pneumoniae. Carbapenemase activity is an unusual feature among class D beta-lactamases, and the structural elements responsible for this activity remain unclear. Based on structural and molecular dynamics data, we previously hypothesized a potential role of the residues located in the short-loop connecting strands beta5 and beta6 (the beta5-beta6 loop) in conferring the carbapenemase activity of the OXA-48 enzyme. In this work, the narrow-spectrum OXA-10 class D beta-lactamase, which is unable to hydrolyze carbapenems, was used as a model to investigate the possibility of evolving carbapenemase activity by replacement of the beta5-beta6 loop with those present in three different lineages of class D carbapenemases (OXA-23, OXA-24, and OXA-48). Biological assays and kinetic measurements showed that all three OXA 10-derived hybrids acquired significant carbapenemase activity. Structural analysis of the OXA-10loop24 and OXA-10loop48 hybrids revealed no significant changes in the molecular fold of the enzyme, except for the orientation of the substituted beta5-beta6 loops, which was reminiscent of that found in their parental enzymes. These results demonstrate the crucial role of the beta5-beta6 loop in the carbapenemase activity of class D beta-lactamases, and provide previously unexplored insights into the mechanism by which these enzymes can evolve carbapenemase activity. PMID- 22042845 TI - Positive affect measured using ecological momentary assessment and survival in older men and women. AB - Links between positive affect (PA) and health have predominantly been investigated by using measures of recollected emotional states. Ecological momentary assessment is regarded as a more precise measure of experienced well being. We analyzed data from the English Longitudinal Study of Aging, a representative cohort of older men and women living in England. PA was assessed by aggregating momentary assessments over a single day in 3,853 individuals aged 52 to 79 y who were followed up for an average of 5 y. Respondents in the lowest third of PA had a death rate of 7.3%, compared with 4.6% in the medium-PA group and 3.6% in the high-PA group. Cox proportional-hazards regression showed a hazard ratio of 0.498 (95% confidence interval, 0.345-0.721) in the high-PA compared with the low-PA group, adjusted for age and sex. This was attenuated to 0.646 (95% confidence interval, 0.436-0.958) after controlling for demographic factors, negative affect, depressed mood, health indicators, and health behaviors. Negative affect and depressed mood were not related to survival after adjustment for covariates. These findings indicate that experienced PA, even over a single day, has a graded relationship with survival that is not caused by baseline health status or other covariates. Momentary PA may be causally related to survival, or may be a marker of underlying biological, behavioral, or temperamental factors, although reverse causality cannot be conclusively ruled out. The results endorse the value of assessing experienced affect, and the importance of evaluating interventions that promote happiness in older populations. PMID- 22042846 TI - Archaic human ancestry in East Asia. AB - Recent studies of ancient genomes have suggested that gene flow from archaic hominin groups to the ancestors of modern humans occurred on two separate occasions during the modern human expansion out of Africa. At the same time, decreasing levels of human genetic diversity have been found at increasing distance from Africa as a consequence of human expansion out of Africa. We analyzed the signal of archaic ancestry in modern human populations, and we investigated how serial founder models of human expansion affect the signal of archaic ancestry using simulations. For descendants of an archaic admixture event, we show that genetic drift coupled with ascertainment bias for common alleles can cause artificial but largely predictable differences in similarity to archaic genomes. In genotype data from non-Africans, this effect results in a biased genetic similarity to Neandertals with increasing distance from Africa. However, in addition to the previously reported gene flow between Neandertals and non-Africans as well as gene flow between an archaic human population from Siberia ("Denisovans") and Oceanians, we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome--a pattern that is not expected under a model of solely Neandertal admixture in the ancestry of East Asians. These results suggest admixture between Denisovans or a Denisova related population and the ancestors of East Asians, and that the history of anatomically modern and archaic humans might be more complex than previously proposed. PMID- 22042847 TI - Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella. AB - Unlike broad-host Salmonella serovars, which cause self-limiting disease, Salmonella enterica serovar Typhi can infect only humans causing typhoid fever, a life-threatening systemic disease. The molecular bases for these differences are presently unknown. Here we show that the GTPase Rab29 (Rab7L1) distinguishes the intracellular vacuole of human-adapted and broad-host Salmonella serovars. A screen to identify host factors required for the export of typhoid toxin, which is exclusively encoded by the human-specific Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi (S. Paratyphi) identified Rab29. We found that Rab29 is recruited to the S. Typhi-containing vacuole but not to vacuoles containing broad host Salmonella. We observed that in cells infected with broad-host Salmonella Rab29 is specifically cleaved by the proteolytic activity of GtgE, a unique type III secretion effector protein that is absent from S. Typhi. An S. Typhi strain engineered to express GtgE and therefore able to cleave Rab29 exhibited increased intracellular replication in human macrophages. These findings indicate significant differences in the intracellular biology of human-adapted and broad host Salmonella and show how subtle differences in the assortment of effector proteins encoded by highly related pathogens can have a major impact in their biology. PMID- 22042848 TI - Comparing shapes, understanding evolution. PMID- 22042849 TI - Long-term RNA interference gene therapy in a dominant retinitis pigmentosa mouse model. AB - RNA interference (RNAi) gene silencing is a potential therapeutic strategy for dominant retinal degeneration disorders. We used self-complementary (sc) AAV2/8 vector to develop an RNAi-based gene therapy in a dominant retinal degeneration mouse model expressing bovine GCAP1(Y99C). We established an in vitro shRNA screening assay based on EGFP-tagged bovine GCAP1, and identified a shRNA that effectively silenced the bovine GCAP1 transgene with ~80% efficiency. Subretinal injection of scAAV2/8 carrying shRNA expression cassette showed robust expression as early as 1 wk after injection. The gene silencing significantly improved photoreceptor survival, delayed disease onset, and increased visual function. Our results provide a promising strategy toward effective RNAi-based gene therapy by scAAV2/8 delivery for dominant retinal diseases. PMID- 22042850 TI - Estrogen-related receptor-alpha is a metabolic regulator of effector T-cell activation and differentiation. AB - Stimulation of resting CD4(+) T lymphocytes leads to rapid proliferation and differentiation into effector (Teff) or inducible regulatory (Treg) subsets with specific functions to promote or suppress immunity. Importantly, Teff and Treg use distinct metabolic programs to support subset specification, survival, and function. Here, we describe that the orphan nuclear receptor estrogen-related receptor-alpha (ERRalpha) regulates metabolic pathways critical for Teff. Resting CD4(+) T cells expressed low levels of ERRalpha protein that increased on activation. ERRalpha deficiency reduced activated T-cell numbers in vivo and cytokine production in vitro but did not seem to modulate immunity through inhibition of activating signals or viability. Rather, ERRalpha broadly affected metabolic gene expression and glucose metabolism essential for Teff. In particular, up-regulation of Glut1 protein, glucose uptake, and mitochondrial processes were suppressed in activated ERRalpha(-/-) T cells and T cells treated with two chemically independent ERRalpha inhibitors or by shRNAi. Acute ERRalpha inhibition also blocked T-cell growth and proliferation. This defect appeared as a result of inadequate glucose metabolism, because provision of lipids, but not increased glucose uptake or pyruvate, rescued ATP levels and cell division. Additionally, we have shown that Treg requires lipid oxidation, whereas Teff uses glucose metabolism, and lipid addition selectively restored Treg--but not Teff- generation after acute ERRalpha inhibition. Furthermore, in vivo inhibition of ERRalpha reduced T-cell proliferation and Teff generation in both immunization and experimental autoimmune encephalomyelitis models. Thus, ERRalpha is a selective transcriptional regulator of Teff metabolism that may provide a metabolic means to modulate immunity. PMID- 22042851 TI - Natural killer (NK)-dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells. AB - Natural killer (NK) cells contribute to not only innate but also to adaptive immunity by interacting with dendritic cells (DCs) and T cells. All activated human NK cells express HLA-DR and can initiate MHCII-dependent CD4(+) T-cell proliferation; however, the expression of MHCII by mouse NK cells and its functional significance are controversial. In this study, we show that NK-DC interactions result in the emergence of MHCII-positive NK cells. Upon in vitro or in vivo activation, mouse conventional NK cells did not induce MHCII transcripts, but rapidly acquired MHCII protein from DCs. MHCII H2-Ab1-deficient NK cells turned I-A(b)-positive when adoptively transferred into wild-type mice or when cultured with WT splenic DCs. NK acquisition of MHCII was mediated by intercellular membrane transfer called "trogocytosis," but not upon DAP10/12- and MHCI-binding NK cell receptor signaling. MHCII-dressed NK cells concurrently acquired costimulatory molecules such as CD80 and CD86 from DCs; however, their expression did not reach functional levels. Therefore, MHCII-dressed NK cells inhibited DC-induced CD4(+) T-cell responses rather than activated CD4(+) T cells by competitive antigen presentation. In a mouse model for delayed-type hypersensitivity, adoptive transfer of MHCII-dressed NK cells attenuated footpad swelling. These results suggest that MHCII-dressed NK cells generated through NK DC interactions regulate T cell-mediated immune responses. PMID- 22042852 TI - Light-dependent attenuation of phycoerythrin gene expression reveals convergent evolution of green light sensing in cyanobacteria. AB - The colorful process of chromatic acclimation allows many cyanobacteria to change their pigmentation in response to ambient light color changes. In red light, cells produce red-absorbing phycocyanin (PC), whereas in green light, green absorbing phycoerythrin (PE) is made. Controlling these pigment levels increases fitness by optimizing photosynthetic activity in different light color environments. The light color sensory system controlling PC expression is well understood, but PE regulation has not been resolved. In the filamentous cyanobacterium Fremyella diplosiphon UTEX 481, two systems control PE synthesis in response to light color. The first is the Rca pathway, a two-component system controlled by a phytochrome-class photoreceptor, which transcriptionally represses cpeCDESTR (cpeC) expression during growth in red light. The second is the Cgi pathway, which has not been characterized. We determined that the Cgi system also regulates PE synthesis by repressing cpeC expression in red light, but acts posttranscriptionally, requiring the region upstream of the CpeC translation start codon. cpeC RNA stability was comparable in F. diplosiphon cells grown in red and green light, and a short transcript that included the 5' region of cpeC was detected, suggesting that the Cgi system operates by transcription attenuation. The roles of four predicted stem-loop structures within the 5' region of cpeC RNA were analyzed. The putative stem-loop 31 nucleotides upstream of the translation start site was required for Cgi system function. Thus, the Cgi system appears to be a unique type of signal transduction pathway in which the attenuation of cpeC transcription is regulated by light color. PMID- 22042853 TI - Crucial role for TNF receptor-associated factor 2 (TRAF2) in regulating NFkappaB2 signaling that contributes to autoimmunity. AB - TNF receptor-associated factor 2 (TRAF2) is a key intracellular signaling mediator that acts downstream of not only TNFalpha but also various members of the TNFalpha superfamily. Here, we report that, despite their lack of TNFalpha signaling, TRAF2(-/-)TNFalpha(-/-) mice develop an inflammatory disorder characterized by autoantibody accumulation and organ infiltration by T cells with the phenotypes of activated, effector, and memory cells. RAG1(-/-) mice reconstituted with TRAF2(-/-)TNFalpha(-/-) bone marrow cells showed increased numbers of hyperactive T cells and rapidly developed progressive and eventually lethal inflammation. No inflammation was observed in RAG1(-/-) mice reconstituted with TRAF2(-/-)TNFalpha(-/-)T-cell receptor beta(-/-) or TRAF2(-/-)TNFalpha(-/ )NFkappaB-induced kinase(+/-) bone marrow cells. The pathogenic TRAF2(-/ )TNFalpha(-/-) T cells showed constitutive NFkappaB2p52 activation and produced elevated levels of T-helper 1 and T-helper 17 cytokines. Our results suggest that a regulatory circuit consisting of TRAF2-NFkappaB-induced kinase-NFkappaB2p52 is essential for the proper control of effector T-cell polarization and that loss of T-cell TRAF2 function induces constitutive NFkappaB2p52 activity that drives fatal autoimmune inflammation independently of TNFalpha signaling. The involvement of this regulatory circuit in controlling autoimmune responses highlights the delicate balance required to avoid paradoxical adverse events when implementing new targeted anti-inflammatory therapies. PMID- 22042854 TI - Depletion of beta-catenin from mature hepatocytes of mice promotes expansion of hepatic progenitor cells and tumor development. AB - Depletion of beta-catenin impairs regeneration of the rapid turn-over gut epithelial cells, but appears dispensable for that of the slow turn-over mature hepatocytes in mice until 1 y of age. As the life span of mature murine hepatocytes is about 400 d, we studied conditional beta-catenin knockout mice (Alb-Cre;Ctnnb1(flx/flx)) until 20 mo of age to determine the function of beta catenin in the postnatal liver. beta-catenin was absent from the hepatocytes of beta-catenin knockout mice 4 wk after delivery. From 9 mo of age, hepatocytes were gradually replaced by newly formed beta-catenin-positive hepatocytes, which constituted about 90% of hepatocytes at 18-20 mo of age. This process was accompanied by active proliferation of bile duct/ductule cells. beta-catenin positive hepatocytes exhibited elevated proliferation activity and expression of progenitor cell markers, but lower albumin and Cre. This might explain their intact beta-catenin protein, and suggest their origins from hepatic progenitor cells. Liver tumors arose spontaneously from beta-catenin-positive cells, and tumorigenesis was accelerated by hepatitis B X protein. These results indicate beta-catenin critical for the regeneration of mature hepatocytes. Failure to regenerate mature hepatocytes results in proliferation of hepatic progenitor cells that are able to maintain liver function but are predisposed to form liver tumors. PMID- 22042855 TI - Ancient DNA suggests the leading role played by men in the Neolithic dissemination. AB - The impact of the Neolithic dispersal on the western European populations is subject to continuing debate. To trace and date genetic lineages potentially brought during this transition and so understand the origin of the gene pool of current populations, we studied DNA extracted from human remains excavated in a Spanish funeral cave dating from the beginning of the fifth millennium B.C. Thanks to a "multimarkers" approach based on the analysis of mitochondrial and nuclear DNA (autosomes and Y-chromosome), we obtained information on the early Neolithic funeral practices and on the biogeographical origin of the inhumed individuals. No close kinship was detected. Maternal haplogroups found are consistent with pre-Neolithic settlement, whereas the Y-chromosomal analyses permitted confirmation of the existence in Spain approximately 7,000 y ago of two haplogroups previously associated with the Neolithic transition: G2a and E1b1b1a1b. These results are highly consistent with those previously found in Neolithic individuals from French Late Neolithic individuals, indicating a surprising temporal genetic homogeneity in these groups. The high frequency of G2a in Neolithic samples in western Europe could suggest, furthermore, that the role of men during Neolithic dispersal could be greater than currently estimated. PMID- 22042856 TI - Large-scale production of functional human serum albumin from transgenic rice seeds. AB - Human serum albumin (HSA) is widely used in clinical and cell culture applications. Conventional production of HSA from human blood is limited by the availability of blood donation and the high risk of viral transmission from donors. Here, we report the production of Oryza sativa recombinant HSA (OsrHSA) from transgenic rice seeds. The level of OsrHSA reached 10.58% of the total soluble protein of the rice grain. Large-scale production of OsrHSA generated protein with a purity >99% and a productivity rate of 2.75 g/kg brown rice. Physical and biochemical characterization of OsrHSA revealed it to be equivalent to plasma-derived HSA (pHSA). The efficiency of OsrHSA in promoting cell growth and treating liver cirrhosis in rats was similar to that of pHSA. Furthermore, OsrHSA displays similar in vitro and in vivo immunogenicity as pHSA. Our results suggest that a rice seed bioreactor produces cost-effective recombinant HSA that is safe and can help to satisfy an increasing worldwide demand for human serum albumin. PMID- 22042857 TI - Cell-autonomous circadian clock of hepatocytes drives rhythms in transcription and polyamine synthesis. AB - The circadian clock generates daily rhythms in mammalian liver processes, such as glucose and lipid homeostasis, xenobiotic metabolism, and regeneration. The mechanisms governing these rhythms are not well understood, particularly the distinct contributions of the cell-autonomous clock and central pacemaker to rhythmic liver physiology. Through microarray expression profiling in Met murine hepatocytes (MMH)-D3, we identified over 1,000 transcripts that exhibit circadian oscillations, demonstrating that the cell-autonomous clock can drive many rhythms, and that MMH-D3 is a valid circadian model system. The genes represented by these circadian transcripts displayed both cophasic and antiphasic organization within a protein-protein interaction network, suggesting the existence of competition for binding sites or partners by genes of disparate transcriptional phases. Multiple pathways displayed enrichment in MMH-D3 circadian transcripts, including the polyamine synthesis module of the glutathione metabolic pathway. The polyamine synthesis module, which is highly associated with cell proliferation and whose products are required for initiation of liver regeneration, includes enzymes whose transcripts exhibit circadian oscillations, such as ornithine decarboxylase and spermidine synthase. Metabolic profiling revealed that the enzymatic product of spermidine synthase, spermidine, cycles as well. Thus, the cell-autonomous hepatocyte clock can drive a significant amount of transcriptional rhythms and orchestrate physiologically relevant modules such as polyamine synthesis. PMID- 22042858 TI - Tomosyn-dependent regulation of synaptic transmission is required for a late phase of associative odor memory. AB - Synaptic vesicle secretion requires the assembly of fusogenic SNARE complexes. Consequently proteins that regulate SNARE complex formation can significantly impact synaptic strength. The SNARE binding protein tomosyn has been shown to potently inhibit exocytosis by sequestering SNARE proteins in nonfusogenic complexes. The tomosyn-SNARE interaction is regulated by protein kinase A (PKA), an enzyme implicated in learning and memory, suggesting tomosyn could be an important effector in PKA-dependent synaptic plasticity. We tested this hypothesis in Drosophila, in which the role of the PKA pathway in associative learning has been well established. We first determined that panneuronal tomosyn knockdown by RNAi enhanced synaptic strength at the Drosophila larval neuromuscular junction, by increasing the evoked response duration. We next assayed memory performance 3 min (early memory) and 3 h (late memory) after aversive olfactory learning. Whereas early memory was unaffected by tomosyn knockdown, late memory was reduced by 50%. Late memory is a composite of stable and labile components. Further analysis determined that tomosyn was specifically required for the anesthesia-sensitive, labile component, previously shown to require cAMP signaling via PKA in mushroom bodies. Together these data indicate that tomosyn has a conserved role in the regulation of synaptic transmission and provide behavioral evidence that tomosyn is involved in a specific component of late associative memory. PMID- 22042859 TI - Intracellular neutralization of viral infection in polarized epithelial cells by neonatal Fc receptor (FcRn)-mediated IgG transport. AB - IgG was traditionally thought to neutralize virions by blocking their attachment to or penetration into mucosal epithelial cells, a common site of exposure to viruses. However, we describe an intracellular neutralizing action for an influenza hemagglutinin-specific monoclonal antibody, Y8-10C2 (Y8), which has neutralizing activity only at an acidic pH. When Y8 was applied to the basolateral surface of Madin-Darby canine kidney cells expressing the rat neonatal Fc receptor for IgG (FcRn), it significantly reduced viral replication following apical exposure of the cell monolayer to influenza virus. Virus neutralization by Y8 mAb was dependent on FcRn expression and its transport of IgG. As both FcRn and Y8 mAb bind their partners only at acidic pH, the Y8 mAb is proposed to carry out its antiviral activity intracellularly. Furthermore, the virus, Y8 mAb, and FcRn colocalized within endosomes, possibly inhibiting the fusion of viral envelopes with endosomal membranes during primary uncoating, and preventing the accumulation of the neutralized viral nucleoprotein antigen in the nucleus. Prophylactic administration of Y8 mAb before viral challenge in WT mice, but not FcRn-KO mice, conferred protection from lethality, prevented weight loss, resulted in a significant reduction in pulmonary virus titers, and largely reduced virus-induced lung pathology. Thus, this study reveals an intracellular mechanism for viral neutralization in polarized epithelial cells that is dependent on FcRn-mediated transport of neutralizing IgG. PMID- 22042860 TI - High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer. AB - Heat-shock factor 1 (HSF1) is the master transcriptional regulator of the cellular response to heat and a wide variety of other stressors. We previously reported that HSF1 promotes the survival and proliferation of malignant cells. At this time, however, the clinical and prognostic significance of HSF1 in cancer is unknown. To address this issue breast cancer samples from 1,841 participants in the Nurses' Health Study were scored for levels of nuclear HSF1. Associations of HSF1 status with clinical parameters and survival outcomes were investigated by Kaplan-Meier analysis and Cox proportional hazard models. The associations were further delineated by Kaplan-Meier analysis using publicly available mRNA expression data. Our results show that nuclear HSF1 levels were elevated in ~80% of in situ and invasive breast carcinomas. In invasive carcinomas, HSF1 expression was associated with high histologic grade, larger tumor size, and nodal involvement at diagnosis (P < 0.0001). By using multivariate analysis to account for the effects of covariates, high HSF1 levels were found to be independently associated with increased mortality (hazards ratio: 1.62; 95% confidence interval: 1.21-2.17; P < 0.0013). This association was seen in the estrogen receptor (ER)-positive population (hazards ratio: 2.10; 95% confidence interval: 1.45-3.03; P < 0.0001). In public expression profiling data, high HSF1 mRNA levels were also associated with an increase in ER-positive breast cancer specific mortality. We conclude that increased HSF1 is associated with reduced breast cancer survival. The findings indicate that HSF1 should be evaluated prospectively as an independent prognostic indicator in ER-positive breast cancer. HSF1 may ultimately be a useful therapeutic target in cancer. PMID- 22042861 TI - CD47-signal regulatory protein-alpha (SIRPalpha) interactions form a barrier for antibody-mediated tumor cell destruction. AB - Monoclonal antibodies are among the most promising therapeutic agents for treating cancer. Therapeutic cancer antibodies bind to tumor cells, turning them into targets for immune-mediated destruction. We show here that this antibody mediated killing of tumor cells is limited by a mechanism involving the interaction between tumor cell-expressed CD47 and the inhibitory receptor signal regulatory protein-alpha (SIRPalpha) on myeloid cells. Mice that lack the SIRPalpha cytoplasmic tail, and hence its inhibitory signaling, display increased antibody-mediated elimination of melanoma cells in vivo. Moreover, interference with CD47-SIRPalpha interactions by CD47 knockdown or by antagonistic antibodies against CD47 or SIRPalpha significantly enhances the in vitro killing of trastuzumab-opsonized Her2/Neu-positive breast cancer cells by phagocytes. Finally, the response to trastuzumab therapy in breast cancer patients appears correlated to cancer cell CD47 expression. These findings demonstrate that CD47 SIRPalpha interactions participate in a homeostatic mechanism that restricts antibody-mediated killing of tumor cells. This provides a rational basis for targeting CD47-SIRPalpha interactions, using for instance the antagonistic antibodies against human SIRPalpha described herein, to potentiate the clinical effects of cancer therapeutic antibodies. PMID- 22042862 TI - Genetic dissection of the biotic stress response using a genome-scale gene network for rice. AB - Rice is a staple food for one-half the world's population and a model for other monocotyledonous species. Thus, efficient approaches for identifying key genes controlling simple or complex traits in rice have important biological, agricultural, and economic consequences. Here, we report on the construction of RiceNet, an experimentally tested genome-scale gene network for a monocotyledonous species. Many different datasets, derived from five different organisms including plants, animals, yeast, and humans, were evaluated, and 24 of the most useful were integrated into a statistical framework that allowed for the prediction of functional linkages between pairs of genes. Genes could be linked to traits by using guilt-by-association, predicting gene attributes on the basis of network neighbors. We applied RiceNet to an important agronomic trait, the biotic stress response. Using network guilt-by-association followed by focused protein-protein interaction assays, we identified and validated, in planta, two positive regulators, LOC_Os01g70580 (now Regulator of XA21; ROX1) and LOC_Os02g21510 (ROX2), and one negative regulator, LOC_Os06g12530 (ROX3). These proteins control resistance mediated by rice XA21, a pattern recognition receptor. We also showed that RiceNet can accurately predict gene function in another major monocotyledonous crop species, maize. RiceNet thus enables the identification of genes regulating important crop traits, facilitating engineering of pathways critical to crop productivity. PMID- 22042863 TI - Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. AB - Ablation of the kinases Mst1 and Mst2, orthologs of the Drosophila antiproliferative kinase Hippo, from mouse intestinal epithelium caused marked expansion of an undifferentiated stem cell compartment and loss of secretory cells throughout the small and large intestine. Although median survival of mice lacking intestinal Mst1/Mst2 is 13 wk, adenomas of the distal colon are common by this age. Diminished phosphorylation, enhanced abundance, and nuclear localization of the transcriptional coactivator Yes-associated protein 1 (Yap1) is evident in Mst1/Mst2-deficient intestinal epithelium, as is strong activation of beta-catenin and Notch signaling. Although biallelic deletion of Yap1 from intestinal epithelium has little effect on intestinal development, inactivation of a single Yap1 allele reduces Yap1 polypeptide abundance to nearly wild-type levels and, despite the continued Yap hypophosphorylation and preferential nuclear localization, normalizes epithelial structure. Thus, supraphysiologic Yap polypeptide levels are necessary to drive intestinal stem cell proliferation. Yap is overexpressed in 68 of 71 human colon cancers and in at least 30 of 36 colon cancer-derived cell lines. In colon-derived cell lines where Yap is overabundant, its depletion strongly reduces beta-catenin and Notch signaling and inhibits proliferation and survival. These findings demonstrate that Mst1 and Mst2 actively suppress Yap1 abundance and action in normal intestinal epithelium, an antiproliferative function that frequently is overcome in colon cancer through Yap1 polypeptide overabundance. The dispensability of Yap1 in normal intestinal homeostasis and its potent proliferative and prosurvival actions when overexpressed in colon cancer make it an attractive therapeutic target. PMID- 22042864 TI - Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription. AB - Mice deficient for interferon regulatory factor (Irf)2 (Irf2(-/-) mice) exhibit immunological abnormalities and cannot survive lymphocytic choriomeningitis virus infection. The pancreas of these animals is highly inflamed, a phenotype replicated by treatment with poly(I:C), a synthetic double-stranded RNA. Trypsinogen5 mRNA was constitutively up-regulated about 1,000-fold in Irf2(-/-) mice compared with controls as assessed by quantitative RT-PCR. Further knockout of IFNalpha/beta receptor 1(Ifnar1) abolished poly(I:C)-induced pancreatitis but had no effect on the constitutive up-regulation of trypsinogen5 gene, indicating crucial type I IFN signaling to elicit the inflammation. Analysis of Ifnar1(-/-) mice confirmed type I IFN-dependent transcriptional activation of dsRNA-sensing pattern recognition receptor genes MDA5, RIG-I, and TLR3, which induced poly(I:C) dependent cell death in acinar cells in the absence of IRF2. We speculate that Trypsin5, the trypsinogen5 gene product, leaking from dead acinar cells triggers a chain reaction leading to lethal pancreatitis in Irf2(-/-) mice because it is resistant to a major endogenous trypsin inhibitor, Spink3. PMID- 22042865 TI - Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes. AB - Sickle cell disease (SCD) is a hematologic disorder caused by a missense mutation in the adult beta-globin gene. Higher fetal hemoglobin (HbF) levels in red blood cells of SCD patients have been shown to improve morbidity and mortality. We previously found that nuclear receptors TR2 and TR4 repress expression of the human embryonic epsilon-globin and fetal gamma-globin genes in definitive erythroid cells. Because forced expression of TR2/TR4 in murine adult erythroid cells paradoxically enhanced fetal gamma-globin gene expression in transgenic mice, we wished to determine if forced TR2/TR4 expression in a SCD model mouse would result in elevated HbF synthesis and thereby alleviate the disease phenotype. In a "humanized" sickle cell model mouse, forced TR2/TR4 expression increased HbF abundance from 7.6% of total hemoglobin to 18.6%, accompanied by increased hematocrit from 23% to 34% and reticulocyte reduction from 61% to 18%, indicating a significant reduction in hemolysis. Moreover, forced TR2/TR4 expression reduced hepatosplenomegaly and liver parenchymal necrosis and inflammation in SCD mice, indicating alleviation of usual pathophysiological characteristics. This article shows that genetic manipulation of nonglobin proteins, or transcription factors regulating globin gene expression, can ameliorate the disease phenotype in a SCD model animal. This proof-of-concept study demonstrates that modulating TR2/TR4 activity in SCD patients may be a promising therapeutic approach to induce persistent HbF accumulation and for treatment of the disease. PMID- 22042866 TI - A chemical-genetic screen to unravel the genetic network of CDC28/CDK1 links ubiquitin and Rad6-Bre1 to cell cycle progression. AB - Cyclin-dependent kinases (CDKs) control the eukaryotic cell cycle, and a single CDK, Cdc28 (also known as Cdk1), is necessary and sufficient for cell cycle regulation in the budding yeast Saccharomyces cerevisiae. Cdc28 regulates cell cycle-dependent processes such as transcription, DNA replication and repair, and chromosome segregation. To gain further insight into the functions of Cdc28, we performed a high-throughput chemical-genetic array (CGA) screen aimed at unraveling the genetic network of CDC28. We identified 107 genes that strongly genetically interact with CDC28. Although these genes serve multiple cellular functions, genes involved in cell cycle regulation, transcription, and chromosome metabolism were overrepresented. DOA1, which is involved in maintaining free ubiquitin levels, as well as the RAD6-BRE1 pathway, which is involved in transcription, displayed particularly strong genetic interactions with CDC28. We discovered that DOA1 is important for cell cycle entry by supplying ubiquitin. Furthermore, we found that the RAD6-BRE1 pathway functions downstream of DOA1/ubiquitin but upstream of CDC28, by promoting transcription of cyclins. These results link cellular ubiquitin levels and the Rad6-Bre1 pathway to cell cycle progression. PMID- 22042867 TI - Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue. AB - Clinical studies and mathematical models predict that, to achieve malaria elimination, combination therapies will need to incorporate drugs that block the transmission of Plasmodium falciparum sexual stage parasites to mosquito vectors. Efforts to measure the activity of existing antimalarials on intraerythrocytic sexual stage gametocytes and identify transmission-blocking agents have, until now, been hindered by a lack of quantitative assays. Here, we report an experimental system using P. falciparum lines that stably express gametocyte specific GFP-luciferase reporters, which enable the assessment of dose- and time dependent drug action on gametocyte maturation and transmission. These studies reveal activity of the first-line antimalarial dihydroartemisinin and the partner drugs lumefantrine and pyronaridine against early gametocyte stages, along with moderate inhibition of mature gametocyte transmission to Anopheles mosquitoes. The other partner agents monodesethyl-amodiaquine and piperaquine showed activity only against immature gametocytes. Our data also identify methylene blue as a potent inhibitor of gametocyte development across all stages. This thiazine dye almost fully abolishes P. falciparum transmission to mosquitoes at concentrations readily achievable in humans, highlighting the potential of this chemical class to reduce the spread of malaria. PMID- 22042868 TI - Biliverdin inhibits Toll-like receptor-4 (TLR4) expression through nitric oxide dependent nuclear translocation of biliverdin reductase. AB - The cellular response to an inflammatory stressor requires a proinflammatory cellular activation followed by a controlled resolution of the response to restore homeostasis. We hypothesized that biliverdin reductase (BVR) by binding biliverdin (BV) quells the cellular response to endotoxin-induced inflammation through phosphorylation of endothelial nitric oxide synthase (eNOS). The generated NO, in turn, nitrosylates BVR, leading to nuclear translocation where BVR binds to the Toll-like receptor-4 (TLR4) promoter at the Ap-1 sites to block transcription. We show in macrophages that BV-induced eNOS phosphorylation (Ser 1177) and NO production are mediated in part by Ca(2+)/calmodulin-dependent kinase kinase. Furthermore, we show that BVR is S-nitrosylated on one of three cysteines and that this posttranslational modification is required for BVR mediated signaling. BV-induced nuclear translocation of BVR and inhibition of TLR4 expression is lost in macrophages derived from Enos(-/-) mice. In vivo in mice, BV provides protection from acute liver damage and is dependent on the availability of NO. Collectively, we elucidate a mechanism for BVR in regulating the inflammatory response to endotoxin that requires eNOS-derived NO and TLR4 signaling in macrophages. PMID- 22042869 TI - A homolog of male sex-determining factor SRY cooperates with a transposon-derived CENP-B protein to control sex-specific directed recombination. AB - Schizosaccharomyces pombe cells switch mating type by replacing genetic information at the expressed mat1 locus with sequences copied from mat2-P or mat3 M silent donor loci. The choice of donor locus is dictated by cell type, such that mat2 is the preferred donor in M cells and mat3 is the preferred donor in P cells. Donor choice involves a recombination-promoting complex (RPC) containing Swi2 and Swi5. In P cells, the RPC localizes to a specific DNA element located adjacent to mat3, but in M cells it spreads across the silent mating-type region, including mat2-P. This differential distribution of the RPC regulates nonrandom choice of donors. However, cell-type-specific differences in RPC localization are not understood. Here we show that the mat1-M-encoded factor Mc, which shares structural and functional similarities with the male sex-determining factor SRY, is highly enriched at the swi2 and swi5 loci and promotes elevated levels of RPC components. Loss of Mc reduces Swi2 and Swi5 to levels comparable to those in P cells and disrupts RPC spreading across the mat2/3 region. Mc also localizes to loci expressed preferentially in M cells and to retrotransposon LTRs. We demonstrate that Mc localization at LTRs and at swi2 requires Abp1, a homolog of transposon-derived CENP-B protein and that loss of Abp1 impairs Swi2 protein expression and the donor choice mechanism. These results suggest that Mc modulates levels of recombination factors, which is important for mating-type donor selection and for the biased gene conversion observed during meiosis, where M cells serve as preferential donors of genetic information. PMID- 22042870 TI - Gating charge interactions with the S1 segment during activation of a Na+ channel voltage sensor. AB - Voltage-gated Na(+) channels initiate action potentials during electrical signaling in excitable cells. Opening and closing of the pore of voltage-gated ion channels are mechanically linked to voltage-driven outward movement of the positively charged S4 transmembrane segment in their voltage sensors. Disulfide locking of cysteine residues substituted for the outermost T0 and R1 gating charge positions and a conserved negative charge (E43) at the extracellular end of the S1 segment of the bacterial Na(+) channel NaChBac detects molecular interactions that stabilize the resting state of the voltage sensor and define its conformation. Upon depolarization, the more inward gating charges R2 and R3 engage in these molecular interactions as the S4 segment moves outward to its intermediate and activated states. The R4 gating charge does not disulfide-lock with E43, suggesting an outer limit to its transmembrane movement. These molecular interactions reveal how the S4 gating charges are stabilized in the resting state and how their outward movement is catalyzed by interaction with negatively charged residues to effect pore opening and initiate electrical signaling. PMID- 22042871 TI - FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders. AB - The adult hippocampus plays a central role in memory formation, synaptic plasticity, and neurogenesis. The subgranular zone of the dentate gyrus contains neural progenitor cells with self-renewal and multilineage potency. Transgene expression of familial Alzheimer's disease-linked mutants of beta-amyloid precursor protein (APP) and presenilin-1 leads to a significant inhibition of neurogenesis, which is potentially linked to age-dependent memory loss. To investigate the effect of neurogenesis on cognitive function in a relevant disease model, FGF2 gene is delivered bilaterally to the hippocampi of APP+presenilin-1 bigenic mice via an adenoassociated virus serotype 2/1 hybrid (AAV2/1-FGF2). Animals injected with AAV2/1-FGF2 at a pre- or postsymptomatic stage show significantly improved spatial learning in the radial arm water maze test. A neuropathological investigation demonstrates that AAV2/1-FGF2 injection enhances the number of doublecortin, BrdU/NeuN, and c-fos-positive cells in the dentate gyrus, and the clearance of fibrillar amyloid-beta peptide (Abeta) in the hippocampus. AAV2/1-FGF2 injection also enhances long-term potentiation in another APP mouse model (J20) compared with control AAV2/1-GFP-injected littermates. An in vitro study confirmed the enhanced neurogenesis of mouse neural stem cells by direct AAV2/1-FGF2 infection in an Abeta oligomer-sensitive manner. Further, FGF2 enhances Abeta phagocytosis in primary cultured microglia, and reduces Abeta production from primary cultured neurons after AAV2/1-FGF2 infection. Thus, our data indicate that virus-mediated FGF2 gene delivery has potential as an alternative therapy of Alzheimer's disease and possibly other neurocognitive disorders. PMID- 22042872 TI - Duplication and partitioning in evolution and function of homoeologous Q loci governing domestication characters in polyploid wheat. AB - The Q gene encodes an AP2-like transcription factor that played an important role in domestication of polyploid wheat. The chromosome 5A Q alleles (5AQ and 5Aq) have been well studied, but much less is known about the q alleles on wheat homoeologous chromosomes 5B (5Bq) and 5D (5Dq). We investigated the organization, evolution, and function of the Q/q homoeoalleles in hexaploid wheat (Triticum aestivum L.). Q/q gene sequences are highly conserved within and among the A, B, and D genomes of hexaploid wheat, the A and B genomes of tetraploid wheat, and the A, S, and D genomes of the diploid progenitors, but the intergenic regions of the Q/q locus are highly divergent among homoeologous genomes. Duplication of the q gene 5.8 Mya was likely followed by selective loss of one of the copies from the A genome progenitor and the other copy from the B, D, and S genomes. A recent V(329)-to-I mutation in the A lineage is correlated with the Q phenotype. The 5Bq homoeoalleles became a pseudogene after allotetraploidization. Expression analysis indicated that the homoeoalleles are coregulated in a complex manner. Combined phenotypic and expression analysis indicated that, whereas 5AQ plays a major role in conferring domestication-related traits, 5Dq contributes directly and 5Bq indirectly to suppression of the speltoid phenotype. The evolution of the Q/q loci in polyploid wheat resulted in the hyperfunctionalization of 5AQ, pseudogenization of 5Bq, and subfunctionalization of 5Dq, all contributing to the domestication traits. PMID- 22042874 TI - Transmission of norovirus among NBA players and staff, winter 2010-2011. AB - In December 2010, 24 players and staff members from 13 National Basketball Association teams were affected with gastroenteritis symptoms. Four of 5 stool specimens from ill players and staff tested positive for norovirus genogroup II. We document evidence of transmission both within teams and, potentially, between teams in 2 instances. PMID- 22042873 TI - Garrod's fourth inborn error of metabolism solved by the identification of mutations causing pentosuria. AB - Pentosuria is one of four conditions hypothesized by Archibald Garrod in 1908 to be inborn errors of metabolism. Mutations responsible for the other three conditions (albinism, alkaptonuria, and cystinuria) have been identified, but the mutations responsible for pentosuria remained unknown. Pentosuria, which affects almost exclusively individuals of Ashkenazi Jewish ancestry, is characterized by high levels of the pentose sugar L-xylulose in blood and urine and deficiency of the enzyme L-xylulose reductase. The condition is autosomal-recessive and completely clinically benign, but in the early and mid-20th century attracted attention because it was often confused with diabetes mellitus and inappropriately treated with insulin. Persons with pentosuria were identified from records of Margaret Lasker, who studied the condition in the 1930s to 1960s. In the DCXR gene encoding L-xylulose reductase, we identified two mutations, DCXR c.583DeltaC and DCXR c.52(+1)G > A, each predicted to lead to loss of enzyme activity. Of nine unrelated living pentosuric subjects, six were homozygous for DCXR c.583DeltaC, one was homozygous for DCXR c.52(+1)G > A, and two were compound heterozygous for the two mutant alleles. L-xylulose reductase was not detectable in protein lysates from subjects' cells and high levels of xylulose were detected in their sera, confirming the relationship between the DCXR genotypes and the pentosuric phenotype. The combined frequency of the two mutant DCXR alleles in 1,067 Ashkenazi Jewish controls was 0.0173, suggesting a pentosuria frequency of approximately one in 3,300 in this population. Haplotype analysis indicated that the DCXR c.52(+1)G > A mutation arose more recently than the DCXR c.583DeltaC mutation. PMID- 22042876 TI - Severe pulmonary involvement in a case attributed to domestically acquired Seoul hantavirus in the United States. AB - Hantavirus is known to cause 2 distinct clinical syndromes: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome. Seoul virus is an Old World hantavirus known to cause HFRS. We report a case attributed to domestically acquired Seoul hantavirus with prominent pulmonary involvement and a fatal outcome. PMID- 22042875 TI - Isolation of sochi virus from a fatal case of hantavirus disease with fulminant clinical course. AB - Sochi virus, a novel genetic variant of Dobrava-Belgrade virus, was isolated in cell culture from a fulminant lethal case of hantavirus disease presenting with shock and combined kidney and lung failure. Sochi virus is transmitted to humans from host reservoir Apodemus ponticus and must be considered a life-threatening emerging agent. PMID- 22042877 TI - Methicillin-resistant Staphylococcus aureus (MRSA) isolated from pets living in households with MRSA-infected children. PMID- 22042878 TI - The incidence of necrotizing changes in adults with pneumococcal pneumonia. AB - BACKGROUND: Necrotizing pneumonia is generally considered a rare complication of pneumococcal infection in adults. We systematically studied the incidence of necrotizing changes in adult patients with pneumococcal pneumonia and examined the severity of infection, role of causative serotypes, and association with bacteremia. METHODS: We used a database of all pneumococcal infections identified at our medical center between 2000 and 2010. Original readings of chest X-rays (CXR) and computerized tomography (CT) were noted. Images were then independently reevaluated by 2 radiologists. The severity of disease at admission was assessed using SMART-COP and Pneumonia Outcomes Research Team (PORT) scoring systems. RESULTS: In 351 cases of pneumococcal pneumonia, necrosis was reported in no (0%) original CXR readings and in 6 of 136 (4.4%) CTs. With rereading, 8 of 351 (2.3%) CXR and 15 of 136 (11.0%) CT had necrotizing changes. Overall, these changes were identified in 23 of 351 (6.6%) patients. The incidence of bacteremia and the admitting SMART-COP and PORT scores were similar in patients with and without necrosis (P = 1.00, P = .32, and P = .54, respectively). Type 3 pneumococcus was more commonly isolated from patients with necrosis than from patients without necrosis (P = .05), but 10 other serotypes were also implicated in 16 cases for which the organism was available for typing. CONCLUSIONS: Necrotizing changes in the lungs were seen in 6.6% of a large series of adults with pneumococcal pneumonia but were often overlooked on initial readings. Patients with necrosis were not more likely to have bacteremia or more severe disease. Type 3 pneumococcus was the most commonly identified serotype. PMID- 22042879 TI - Patient reported outcomes in routine care: advancing data capture for HIV cohort research. AB - INTRODUCTION: Computerized collection of standardized measures of patient reported outcomes (PROs) provides a novel paradigm for data capture at the point of clinical care. Comparisons between data from PROs and Electronic Health Records (EHR) are lacking. We compare EHR and PRO for capture of depression and substance abuse and their relationship to adherence to antiretroviral therapy (ART). METHODS: This retrospective study includes HIV-positive patients at an HIV clinic who completed an initial PRO assessment April 2008-July 2009. The questionnaire includes measures of depression (PHQ-9) and substance abuse (ASSIST). Self-reported ART adherence was modeled using separate logistic regression analyses (EHR vs PRO). RESULTS: The study included 782 participants. EHR vs PRO diagnosis of current substance abuse was 13% (n = 99) vs 6% (n = 45) (P < .0001), and current depression was 41% (n = 317) vs 12% (n = 97) (P < .0001). In the EHR model, neither substance abuse (OR = 1.25; 95% CI = 0.70-2.21) nor depression (OR = 0.93; 95% CI = 0.62-1.40) was significantly associated with poor ART adherence. Conversely, in the PRO model, current substance abuse (OR = 2.78; 95% CI = 1.33-5.81) and current depression (OR = 1.93; 95% CI = 1.12-3.33) were associated with poor ART adherence. DISCUSSIONS: The explanatory characteristics of the PRO model correlated best with factors known to be associated with poor ART adherence (substance abuse; depression). The computerized capture of PROs as a part of routine clinical care may prove to be a complementary and potentially transformative health informatics technology for research and patient care. PMID- 22042880 TI - Cardiovascular-emotional dampening: the relationship between blood pressure and recognition of emotion. AB - OBJECTIVE: Persons with elevated blood pressure (BP) show dampened emotional responses to affect-laden stimuli. We sought to further examine cardiovascular emotional dampening by examination of the relationship between resting hemodynamic measures and recognition of emotion in an African American community based sample. METHODS: Participants were 106 African American men and women (55 women; mean age = 52.8 years), mainly low in socioeconomic status, and part of the Healthy Aging in Nationally Diverse Longitudinal Samples pilot study. Participants evaluated emotional expressions in faces and sentences using the Perception of Affect Test (PAT). Resting BP, total peripheral resistance (TPR), cardiac output, and heart rate were obtained continuously using a Portapres BP monitor. RESULTS: Total PAT scores were inversely related to systolic (r = -0.30) and diastolic (r = -0.24) BPs, TPR (r = -0.36), and age (r = -0.31; p values < .01) and were positively related to cardiac output (r = 0.27) and education (r = 0.38; p values < .01), as well as with mental state (r = 0.25) and body mass index (r = -0.20; p values < .05). Accuracy of emotion recognition on the PAT tasks remained inversely related to TPR and BP after adjustment for demographic variables, medication, mental state, and body mass index. CONCLUSIONS: Elevated BP and TPR were associated with reduced perception of affect. TPR was the most consistent independent hemodynamic correlate of emotional dampening for the PAT scores. These results suggest potentially important links among central nervous system regulation of emotions, hemodynamic processes, and hypertension development. PMID- 22042881 TI - Psychosocial predictors of coronary artery calcification progression in postmenopausal women. AB - OBJECTIVE: Coronary artery calcification (CAC) has been associated with psychosocial factors in some but not all cross-sectional analyses. The goal of this study was to determine whether positive and negative psychosocial factors prospectively predict CAC progression in postmenopausal women. METHODS: Participants from the Healthy Women Study who also participated in the Pittsburgh Mind-Body Center protocol (n = 149) completed self-report psychosocial measures before two electron beam computed tomographic scans of CAC separated by an average of 3.3 years. Results of exploratory factor analysis were used to create aggregate psychosocial indices: psychological risk (depressive symptoms, perceived stress, cynicism, and anger-in) and psychosocial resources (optimism, purpose in life, mastery, self-esteem, and social support). RESULTS: The psychological risk index predicted significantly greater CAC progression over 3 years (beta = 0.16, p = .035, DeltaR(2) = 0.03), whereas the psychosocial resources index was not predictive of CAC progression (beta = -0.08, p = .30, DeltaR(2) = 0.01). On individual scales, higher scores on cynicism emerged as a significant predictor of CAC progression, along with a trend linking anger-in to atherosclerosis progression. A post hoc analysis showed a significant interaction between cynicism and anger-in (beta = 0.20, p = .01, DeltaR(2) = 0.03), such that women reporting high levels of both cynicism and anger suppression exhibited the most CAC progression. CONCLUSIONS: These findings highlight psychosocial risk factors that may accelerate the progression of subclinical atherosclerosis in older women, suggest the potential importance of examining combinations of psychosocial risk factors, and identify potential targets for psychological interventions to reduce cardiovascular risk. PMID- 22042882 TI - Prevalence of personality disorders and their clinical correlates in outpatient adolescents with anorexia nervosa. AB - OBJECTIVE: To evaluate personality disorder (PD) comorbidity and its clinical correlates in a sample of adolescents with anorexia nervosa (AN) and to compare them with similar studies on adults. METHODS: One hundred one female AN outpatients (16-18 years old)-57 with AN restrictive type and 44 with AN binge purging type-and 71 age-matched, healthy, female participants were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders. Five selected clinical variables of AN severity were also assessed. RESULTS: Overall, 24.8% of AN outpatients had one or more PD compared with 4.2% of the control participants (p < .001). PDs most frequently found in AN outpatients were avoidant, borderline, and obsessive-compulsive. Associations were found between AN binge purging type and borderline PD and between AN restrictive type and obsessive compulsive PD. AN outpatients with a PD had an earlier age of onset of AN (mean [standard deviation {SD}] = 15.4 [1.2] versus 16.1 [0.9], p = .002), lower lifetime lowest BMI (mean [SD] = 14.8 [1.5] versus 15.6 [1.3], p = .01), and more hospital admissions for AN (mean [SD] = 1.4 [0.9] versus 0.3 [0.6], p < .001) compared with those without PDs. CONCLUSIONS: Associations were found between AN and PDs in adolescents similar to those found in adults. The presence of a PD is associated with a greater severity of AN. PD assessment of adolescent AN patients may permit a more accurate diagnosis and better treatment planning. PMID- 22042883 TI - Trigger-based mechanism of the persistence of atrial fibrillation and its impact on the efficacy of catheter ablation. AB - BACKGROUND: We investigated the possibility that a frequent trigger action might play a role in the development of persistent atrial fibrillation (PeAF) and the presence of a substrate. METHODS AND RESULTS: In 263 consecutive patients who underwent catheter ablation (CA) for PeAF, electric cardioversion was performed at the beginning of the procedure to determine the presence or absence of an immediate recurrence of AF (IRAF). We defined an IRAF as a reproducible AF recurrence within 90 s after restoration of sinus rhythm by electric cardioversion. We performed a mean+/-SD of 1.3+/-0.5 sessions of CA, including pulmonary vein isolation and ablation of the premature atrial contractions that triggered the IRAF (IRAF triggers), and observed the patients for 17 (10-27) months. An IRAF was observed in 70 patients (27%), but we could not ablate the IRAF triggers in 16 (23%) of these IRAF patients. The recurrence rate of PeAF was higher in patients with an unsuccessful IRAF trigger ablation than in those with successful IRAF trigger ablation (63% versus 11%; P<0.001). A multivariable analysis also revealed that an unsuccessful IRAF trigger ablation was 1 of the independent predictors of recurrent PeAF (odds ratio, 10.9; 95% CI, 3.4-36.7). CONCLUSIONS: In the PeAF patients with an IRAF, successful elimination of the IRAF triggers, in addition to pulmonary vein isolation, resulted in a successful CA. These results imply that such triggers play a major role in the AF persistence in these PeAF patients. PMID- 22042885 TI - Derivation and validation of a simple exercise-based algorithm for prediction of genetic testing in relatives of LQTS probands. AB - BACKGROUND: Genetic testing can diagnose long-QT syndrome (LQTS) in asymptomatic relatives of patients with an identified mutation; however, it is costly and subject to availability. The accuracy of a simple algorithm that incorporates resting and exercise ECG parameters for screening LQTS in asymptomatic relatives was evaluated, with genetic testing as the gold standard. METHODS AND RESULTS: Asymptomatic first-degree relatives of genetically characterized probands were recruited from 5 centers. QT intervals were measured at rest, during exercise, and during recovery. Receiver operating characteristics were used to establish optimal cutoffs. An algorithm for identifying LQTS carriers was developed in a derivation cohort and validated in an independent cohort. The derivation cohort consisted of 69 relatives (28 with LQT1, 20 with LQT2, and 21 noncarriers). Mean age was 35+/-18 years, and resting corrected QT interval (QTc) was 466+/-39 ms. Abnormal resting QTc (females >=480 ms; males >=470 ms) was 100% specific for gene carrier status, but was observed in only 48% of patients; however, mutations were observed in 68% and 42% of patients with a borderline or normal resting QTc, respectively. Among these patients, 4-minute recovery QTc >=445 ms correctly restratified 22 of 25 patients as having LQTS and 19 of 21 patients as being noncarriers. The combination of resting and 4-minute recovery QTc in a screening algorithm yielded a sensitivity of 0.94 and specificity of 0.90 for detecting LQTS carriers. When applied to the validation cohort (n=152; 58 with LQT1, 61 with LQT2, and 33 noncarriers; QTc=443+/-47 ms), sensitivity was 0.92 and specificity was 0.82. CONCLUSIONS: A simple algorithm that incorporates resting and exercise-recovery QTc is useful in identifying LQTS in asymptomatic relatives. PMID- 22042884 TI - Association of genetic variants and incident coronary heart disease in multiethnic cohorts: the PAGE study. AB - BACKGROUND: Genome-wide association studies identified several single nucleotide polymorphisms (SNP) associated with prevalent coronary heart disease (CHD), but less is known of associations with incident CHD. The association of 13 published CHD SNPs was examined in 5 ancestry groups of 4 large US prospective cohorts. METHODS AND RESULTS: The analyses included incident coronary events over an average 9.1 to 15.7 follow-up person-years in up to 26 617 white individuals (6626 events), 8018 black individuals (914 events), 1903 Hispanic individuals (113 events), 3669 American Indian individuals (595 events), and 885 Asian/Pacific Islander individuals (66 events). We used Cox proportional hazards models (with additive mode of inheritance) adjusted for age, sex, and ancestry (as needed). Nine loci were statistically associated with incident CHD events in white participants: 9p21 (rs10757278; P=4.7 * 10(-41)), 16q23.1 (rs2549513; P=0.0004), 6p24.1 (rs499818; P=0.0002), 2q36.3 (rs2943634; P=6.7 * 10(-6)), MTHFD1L (rs6922269, P=5.1 * 10(-10)), APOE (rs429358; P=2.7*10(-18)), ZNF627 (rs4804611; P=5.0 * 10(-8)), CXCL12 (rs501120; P=1.4 * 10(-6)) and LPL (rs268; P=2.7 * 10(-17)). The 9p21 region showed significant between-study heterogeneity, with larger effects in individuals age 55 years or younger and in women. Inclusion of coronary revascularization procedures among the incident CHD events introduced heterogeneity. The SNPs were not associated with CHD in black participants, and associations varied in other US minorities. CONCLUSIONS: Prospective analyses of white participants replicated several reported cross sectional CHD-SNP associations. PMID- 22042886 TI - Renal function after catheter ablation of atrial fibrillation. AB - BACKGROUND: Kidney function is a known predictor of cardiovascular morbidity and mortality. Although patients with atrial fibrillation (AF) often have kidney dysfunction, less is known about the association between AF and kidney function. We sought to assess changes in kidney function after catheter ablation of AF. METHODS AND RESULTS: Patients who underwent catheter ablation of AF were recruited for the present prospective study. Estimated glomerular filtration rate (eGFR) was evaluated before and 1 year after the ablation. Three hundred eighty six patients (paroxysmal AF, 135; persistent AF, 106; longstanding persistent AF, 145) were studied. Their baseline eGFR was 68 +/- 14 mL . min(-1) . 1.73 m(-2). Sixty-six percent and 26% of patients had eGFR of 60 to 89 and 30 to 59 mL . min( 1) . 1.73 m(-2), respectively. Overall, 278 patients (72%) were arrhythmia free over a 1-year follow-up. In patients free from arrhythmia, eGFR increased 3 months later and was maintained until 1 year, whereas in patients with recurrences, eGFR had decreased over 1 year. Changes in eGFR over 1 year in patients free from arrhythmia differed significantly compared with those with recurrences (3 +/- 8 versus -2 +/- 8 mL . min(-1) . 1.73 m(-2); P<0.0001). In all quartiles of baseline eGFR, changes in eGFR over 1 year after the ablation were greater in patients free from arrhythmia compared with those with recurrences. CONCLUSION: Elimination of AF by catheter ablation was associated with improvement of kidney function over a 1-year follow-up in patients with mild to moderate kidney dysfunction. PMID- 22042887 TI - Randomized trial of cutting balloon compared with high-pressure angioplasty for the treatment of resistant pulmonary artery stenosis. AB - BACKGROUND: We sought to determine the safety and efficacy of Cutting Balloon therapy (CB) compared with conventional high-pressure balloon therapy (HPB) for the treatment of pulmonary artery stenosis. METHODS AND RESULTS: This prospective, randomized, multicenter, investigational device exemption trial compared CB with HPB. Patient eligibility was determined at the precatheterization assessment; vessel eligibility was determined at catheterization. In all vessels, low-pressure balloon dilation to 8 atm was performed, and if it was not successful, the vessel was randomized to CB or HPB. The primary efficacy outcome was percent change in minimum lumen diameter. A core laboratory performed all vessel measurements and angiographic assessment of vessel damage. The primary safety outcome was any serious adverse event attributable to vessel dilation as assessed by the Data and Safety Monitoring Board. Seventy-three patients from 8 institutions were enrolled between 2004 and 2008. In these patients, 72 vessels responded to low-pressure balloon dilation. Of the 173 vessels that met eligibility criteria, 107 were randomized to CB and 66 to HPB. In randomized vessels, CB therapy was associated with greater percent increase in lumen diameter (85% versus 52%; P=0.004). After crossover was introduced, 26 of 47 vessels treated with HPB underwent CB therapy and experienced an additional 48% increase in lumen diameter; the final diameter after CB was 99% greater than the initial diameter. There were no serious adverse events related to treatment in a study vessel. CONCLUSION: CB therapy for pulmonary artery stenosis not responsive to low-pressure balloon is more effective than HPB therapy and has an equivalent safety profile. PMID- 22042888 TI - Controlling for high-density lipoprotein cholesterol does not affect the magnitude of the relationship between alcohol and coronary heart disease. AB - BACKGROUND: This study tested the hypothesis that moderate alcohol intake exerts its cardioprotective effect mainly through an increase in the serum level of high density lipoprotein cholesterol. METHODS AND RESULTS: In the Cohort of Norway (CONOR) study, 149 729 adult participants, recruited from 1994 to 2003, were followed by linkage to the Cause of Death Registry until 2006. At recruitment, questionnaire data on alcohol intake were collected, and the concentration of high-density lipoprotein cholesterol in serum was measured. Using Cox regression, we found that the adjusted hazard ratio for men for dying from coronary heart disease was 0.52 (95% confidence interval, 0.39-0.69) when consuming alcohol more than once a week compared with never or rarely. The ratio changed only slightly, to 0.55 (0.41-0.73), after the regression model included the serum level of high density cholesterol. For women, the corresponding hazard ratios were 0.62 (0.32 1.23) and 0.68 (0.34-1.34), respectively. CONCLUSIONS: Alcohol intake is related to a reduced risk of death from coronary heart disease in the follow-up of a large, population-based Norwegian cohort study with extensive control for confounding factors. Our findings suggest that the serum level of high-density cholesterol is not an important intermediate variable in the possible causal pathway between moderate alcohol intake and coronary heart disease. PMID- 22042891 TI - Handling uncertainty in science. PMID- 22042892 TI - Science as organized scepticism. AB - Real progress in understanding how the natural world works only truly began with the Enlightenment, with its guiding principle that the truth is to be found not by appeal to authority but by experimental tests and evidence. Unfortunately, but understandably, science is too often seen--in school, in university and especially on quiz shows--as certainty. In fact, science (including social sciences, engineering and medicine along with the more narrowly defined physical and biological sciences) is better seen as organized scepticism: a journey, over time, toward contingent understanding guided by experimental tests and sceptical questioning. Essentially all such journeys are beset by uncertainties of various kinds. This article sketches some of the consequent problems, particularly in relation to science advice, policy making and public engagement. PMID- 22042893 TI - Curious and sublime: the connection between uncertainty and probability in physics. AB - From its first significant appearance in physics, the notion of probability has been linked in the minds of physicists with the notion of uncertainty. But the link may prove to be tenuous, if quantum mechanics, construed in terms of the Everett interpretation, is anything to go by. PMID- 22042894 TI - Sources of uncertainty in deterministic dynamics: an informal overview. AB - The discovery of chaotic dynamics implies that deterministic systems may not be predictable in any meaningful sense. The best-known source of unpredictability is sensitivity to initial conditions (popularly known as the butterfly effect), in which small errors or disturbances grow exponentially. However, there are many other sources of uncertainty in nonlinear dynamics. We provide an informal overview of some of these, with an emphasis on the underlying geometry in phase space. The main topics are the butterfly effect, uncertainty in initial conditions in non-chaotic systems, such as coin tossing, heteroclinic connections leading to apparently random switching between states, topological complexity of basin boundaries, bifurcations (popularly known as tipping points) and collisions of chaotic attractors. We briefly discuss possible ways to detect, exploit or mitigate these effects. The paper is intended for non-specialists. PMID- 22042895 TI - Don't know, can't know: embracing deeper uncertainties when analysing risks. AB - Numerous types of uncertainty arise when using formal models in the analysis of risks. Uncertainty is best seen as a relation, allowing a clear separation of the object, source and 'owner' of the uncertainty, and we argue that all expressions of uncertainty are constructed from judgements based on possibly inadequate assumptions, and are therefore contingent. We consider a five-level structure for assessing and communicating uncertainties, distinguishing three within-model levels--event, parameter and model uncertainty--and two extra-model levels concerning acknowledged and unknown inadequacies in the modelling process, including possible disagreements about the framing of the problem. We consider the forms of expression of uncertainty within the five levels, providing numerous examples of the way in which inadequacies in understanding are handled, and examining criticisms of the attempts taken by the Intergovernmental Panel on Climate Change to separate the likelihood of events from the confidence in the science. Expressing our confidence in the adequacy of the modelling process requires an assessment of the quality of the underlying evidence, and we draw on a scale that is widely used within evidence-based medicine. We conclude that the contingent nature of risk-modelling needs to be explicitly acknowledged in advice given to policy-makers, and that unconditional expressions of uncertainty remain an aspiration. PMID- 22042896 TI - Uncertainty in weather and climate prediction. AB - Following Lorenz's seminal work on chaos theory in the 1960s, probabilistic approaches to prediction have come to dominate the science of weather and climate forecasting. This paper gives a perspective on Lorenz's work and how it has influenced the ways in which we seek to represent uncertainty in forecasts on all lead times from hours to decades. It looks at how model uncertainty has been represented in probabilistic prediction systems and considers the challenges posed by a changing climate. Finally, the paper considers how the uncertainty in projections of climate change can be addressed to deliver more reliable and confident assessments that support decision-making on adaptation and mitigation. PMID- 22042897 TI - Environmental prediction, risk assessment and extreme events: adaptation strategies for the developing world. AB - The uncertainty associated with predicting extreme weather events has serious implications for the developing world, owing to the greater societal vulnerability to such events. Continual exposure to unanticipated extreme events is a contributing factor for the descent into perpetual and structural rural poverty. We provide two examples of how probabilistic environmental prediction of extreme weather events can support dynamic adaptation. In the current climate era, we describe how short-term flood forecasts have been developed and implemented in Bangladesh. Forecasts of impending floods with horizons of 10 days are used to change agricultural practices and planning, store food and household items and evacuate those in peril. For the first time in Bangladesh, floods were anticipated in 2007 and 2008, with broad actions taking place in advance of the floods, grossing agricultural and household savings measured in units of annual income. We argue that probabilistic environmental forecasts disseminated to an informed user community can reduce poverty caused by exposure to unanticipated extreme events. Second, it is also realized that not all decisions in the future can be made at the village level and that grand plans for water resource management require extensive planning and funding. Based on imperfect models and scenarios of economic and population growth, we further suggest that flood frequency and intensity will increase in the Ganges, Brahmaputra and Yangtze catchments as greenhouse-gas concentrations increase. However, irrespective of the climate-change scenario chosen, the availability of fresh water in the latter half of the twenty-first century seems to be dominated by population increases that far outweigh climate-change effects. Paradoxically, fresh water availability may become more critical if there is no climate change. PMID- 22042898 TI - Uncertainty in macroeconomic policy-making: art or science? AB - Uncertainty is pervasive in economic policy-making. Modern economies share similarities with other complex systems in their unpredictability. But economic systems also differ from those in the natural sciences because outcomes are affected by the state of beliefs of the systems' participants. The dynamics of beliefs and how they interact with economic outcomes can be rich and unpredictable. This paper relates these ideas to the recent crisis, which has reminded us that we need a financial system that is resilient in the face of the unpredictable and extreme. It also highlights how such uncertainty puts a premium on sound communication strategies by policy-makers. This creates challenges in informing others about the uncertainties in the economy, and how policy is set in the face of those uncertainties. We show how the Bank of England tries to deal with some of these challenges in its communications about monetary policy. PMID- 22042899 TI - Uncertainty in science and its role in climate policy. AB - Policy-making is usually about risk management. Thus, the handling of uncertainty in science is central to its support of sound policy-making. There is value in scientists engaging in a deep conversation with policy-makers and others, not merely 'delivering' results or analyses and then playing no further role. Communicating the policy relevance of different varieties of uncertainty, including imprecision, ambiguity, intractability and indeterminism, is an important part of this conversation. Uncertainty is handled better when scientists engage with policy-makers. Climate policy aims both to alter future risks (particularly via mitigation) and to take account of and respond to relevant remaining risks (via adaptation) in the complex causal chain that begins and ends with individuals. Policy-making profits from learning how to shift the distribution of risks towards less dangerous impacts, even if the probability of events remains uncertain. Immediate value lies not only in communicating how risks may change with time and how those risks may be changed by action, but also in projecting how our understanding of those risks may improve with time (via science) and how our ability to influence them may advance (via technology and policy design). Guidance on the most urgent places to gather information and realistic estimates of when to expect more informative answers is of immediate value, as are plausible estimates of the risk of delaying action. Risk assessment requires grappling with probability and ambiguity (uncertainty in the Knightian sense) and assessing the ethical, logical, philosophical and economic underpinnings of whether a target of '50 per cent chance of remaining under +2( degrees )C' is either 'right' or 'safe'. How do we better stimulate advances in the difficult analytical and philosophical questions while maintaining foundational scientific work advancing our understanding of the phenomena? And provide immediate help with decisions that must be made now? PMID- 22042900 TI - Risk, uncertainty and regulation. AB - This paper reviews the relationship between scientific evidence, uncertainty, risk and regulation. Risk has many different meanings. Furthermore, if risk is defined as the likelihood of an event happening multiplied by its impact, subjective perceptions of risk often diverge from the objective assessment. Scientific evidence may be ambiguous. Scientific experts are called upon to assess risks, but there is often uncertainty in their assessment, or disagreement about the magnitude of the risk. The translation of risk assessments into policy is a political judgement that includes consideration of the acceptability of the risk and the costs and benefits of legislation to reduce the risk. These general points are illustrated with reference to three examples: regulation of risk from pesticides, control of bovine tuberculosis and pricing of alcohol as a means to discourage excessive drinking. PMID- 22042901 TI - The Department of Health perspective on handling uncertainties in health sciences. AB - Recognizing and working with uncertainty in handling risk are part of both clinical practice and the policy-making process. The Department of Health recognizes the inherent challenges that uncertainty brings and employs a wide range of research mechanisms, drawing on a diverse set of disciplines, to provide an evidence base to inform both policy creation and implementation, and clinical practice. This paper describes a variety of situations and the Government response to them, each time highlighting the use of science to reduce unknowns and to support decision-making. It highlights the need for a strong research infrastructure to support the Department's requirements, and those of the NHS, both in real time to respond to emergencies and to establish a high standard of care. However, although science provides a powerful tool to reduce uncertainty, it will not always produce definitive answers and often provides the start point for a dialogue between decision makers and researchers. PMID- 22042902 TI - Uncertainty in quantum mechanics: faith or fantasy? AB - The word 'uncertainty', in the context of quantum mechanics, usually evokes an impression of an essential unknowability of what might actually be going on at the quantum level of activity, as is made explicit in Heisenberg's uncertainty principle, and in the fact that the theory normally provides only probabilities for the results of quantum measurement. These issues limit our ultimate understanding of the behaviour of things, if we take quantum mechanics to represent an absolute truth. But they do not cause us to put that very 'truth' into question. This article addresses the issue of quantum 'uncertainty' from a different perspective, raising the question of whether this term might be applied to the theory itself, despite its unrefuted huge success over an enormously diverse range of observed phenomena. There are, indeed, seeming internal contradictions in the theory that lead us to infer that a total faith in it at all levels of scale leads us to almost fantastical implications. PMID- 22042903 TI - Understanding the receivers and the reception of science's uncertain messages. AB - Although much work has been done by scientists in developing communications to non-scientist audiences, much less attention has been given by them to the ways in which those messages are interpreted. Here, I look at the published work that examines the issue. I focus on three contexts in particular: debates over the triple vaccine for measles, mumps and rubella, the impacts of the Soufriere Hills volcano on the inhabitants of the island of Montserrat and the public communication of the results of climate change research. Several common themes emerge. The most important conclusions are that scientists communicating with the public need to develop their methods deliberatively, involving their target audiences; and that they need to avoid undue dependence on traditional media and public authorities for such communication, and to develop multiple channels to those audiences, including Internet-based and more traditional social networks. Their approach to communicating uncertainty should depend on the context but, except in some extreme emergencies, transparency is generally a virtue. Above all, they need to persist in such public engagements even when the going is rough and extends over long periods. They need support in doing so. PMID- 22042905 TI - Policy implications of uncertainty. PMID- 22042904 TI - The time resolution of the St Petersburg paradox. AB - A resolution of the St Petersburg paradox is presented. In contrast to the standard resolution, utility is not required. Instead, the time-average performance of the lottery is computed. The final result can be phrased mathematically identically to Daniel Bernoulli's resolution, which uses logarithmic utility, but is derived using a conceptually different argument. The advantage of the time resolution is the elimination of arbitrary utility functions. PMID- 22042908 TI - The Nursing Home Falls Self-Efficacy Scale: development and testing. AB - We examined a brief measure of falls self-efficacy in nursing home residents participating in a pilot randomized controlled trial to study the effects of hip protectors on the prevention of fractures (N = 116, mean age 82 +/- 8, 72% female). Internal consistency reliability was acceptable with Cronbach's alpha of .79. Factor analysis supported two factors representing self-efficacy expectations and outcome expectancy. Contrasted groups comparisons and construct validity were examined. We found lower falls self-efficacy in participants who needed help with mobility, in people with lower executive function, and in participants who reported fear of falling. Scores were not associated with prospective falls or adherence with hip protector use. The findings of this study provide preliminary support for the reliability and validity of the scale for future research. PMID- 22042909 TI - Physical activity and body mass perception. AB - PURPOSE: To evaluate ethnic perceptual variations in body mass index (BMI) and accrued physical activity. Women (n = 204) from the eastern United States were stratified into the following ethnic groups: White women (WW; n = 97), Black women (BW n = 62) and Others (Hispanic and Asian women, n = 45). Participants completed questionnaires and physiologic variables were determined. BW had increased weight, BMI, waist circumference, and body fat percentage vs. WW (p < .05). Body mass was higher in BW vs. Others (p < .05). There were no differences for perception of BMI or body dissatisfaction. BW were the only group in which perception of BMI was lower than measured BMI. BW engaged in 50% less domestic and total physical activity than WW and Others. Physical activity was not correlated to perception of BMI. CONCLUSION: Perception of BMI was similar across ethnic groups and not correlated to physical activity levels in young women. PMID- 22042910 TI - Cardiovascular disease and risk factors in an indigenous minority population. The All-Ireland Traveller Health Study. AB - BACKGROUND: The Traveller community are an indigenous minority group in Great Britain and Ireland who experience premature mortality. While minority populations worldwide are known to have high rates of risk factors for cardiovascular disease (CVD), Traveller CVD risk has not previously been defined. DESIGN: All-Ireland cross-sectional census survey of the Traveller minority population (n = 10,615 families). METHODS: A subsample of adult respondents completed a health survey (n = 2023). CVD was defined as self-report of doctor diagnosed heart attack, angina, or stroke. CVD risk factors and measures of social position were examined in the Traveller group using age-adjusted prevalence and prevalence ratios (PR). Comparisons were made with a general population sample of low socioeconomic status. RESULTS: Age-adjusted prevalence of CVD in the Traveller population was 5.6% (95% CI 4.6-6.8), similar to that in the comparator population. Compared to those without CVD, Travellers with CVD had a higher prevalence of self-report of diabetes, hypertension, hypercholesterolaemia, current smoking, and a measure of distrust. Compared with the general population sample, Travellers had a higher prevalence of diabetes (adjusted PR 2.8, 95% CI 2.1-3.8) and lifestyle-related risk factors such as smoking (PR 1.3, 95% CI 1.2-1.4), fried food consumption (PR 2.8, 95% CI 2.4 3.2), and physical inactivity (PR 1.3, 95% CI 1.2-1.4). CONCLUSIONS: This comprehensive census survey confirms CVD as an important health risk in the economically disadvantaged Irish Traveller community. Our findings add to the international knowledge base on minority populations and CVD risk. PMID- 22042911 TI - Cellular resistance to HIV-1 infection in target cells coincides with a rapid induction of X-DING-CD4 mRNA: indication of the unique host innate response to virus regulated through function of the X-DING-CD4 gene. AB - Clinical reports indicate that some infected individuals control HIV-1 replication through undefined mechanisms. Our group reported that a human protein named X-DING-CD4 holds a potent antiviral activity, blocking transcription of HIV 1 LTR through the inhibition of NF-kappaB/DNA binding. Based on observations that transformed HIV-1 resistant CD4(+) T cells produce higher levels of soluble X DING-CD4 protein upon their exposure to virus, we hypothesized that resistance to HIV-1 in these cells may be regulated through function of the X-DING-CD4 gene. Real-time PCR evaluations of X-DING-CD4 mRNA expression confirmed our hypothesis; HIV-1 exposure caused rapid up-regulation of X-DING-CD4 mRNA in resistant, but not susceptible, cells; and the burst of X-DING-CD4 mRNA expression correlated with restriction of HIV-1 transcription. Subsequently, we examined the activity of the X-DING-CD4 gene in monocytes and macrophages from (n = 13) HIV-negative donors. The assessment of HIV-1 gag mRNA showed that the majority of cells were permissive to virus replication; however, macrophages from four donors were refractory to HIV-1 infection. In response to virus, these cells up-regulated X DING-CD4 gene expression by 2- to 1000-fold. These data provide evidence that the X-DING-CD4 gene contributes to early cellular protection from HIV infection in some individuals and this protection depends solely on the unique genetic regulation of the host. PMID- 22042912 TI - Fever induction by systemic stimulation with macrophage-activating lipopeptide-2 depends upon TLR2 but not CD36. AB - This study was designed to test the responses of TLR2-knockout mice (TLR2-KO) and wild- type mice (C57/BL-6), and of CD36 deficient spontaneously hypertensive rats (SHR) and their genetic controls [Wistar Kyoto (WKY) rats] to systemic stimulations with the TLR2/6 agonist MALP-2 and the TLR4 agonist LPS. Fever and formation of TNF-alpha and IL-6 induced by intraperitoneal injections of MALP-2 (1000 ug/kg) were completely blunted in TLR2-KO, while LPS (100 ug/kg)-induced responses were not abolished in these animals. In SHR lacking CD36, a reduction of fever was observed in response to MALP-2 (100 ug/kg), but LPS-fever was even more attenuated in SHR when compared with WKY controls. Concentrations of circulating IL-6 tended to be lower in SHR after stimulation with both pyrogens. However, the IL-6-mediated activation of the transcription factor STAT3 in the brain was identical in both strains, indicating that the brain-controlled inflammatory response to MALP-2 (and LPS) is not impaired in the absence of CD36. In addition, stimulation of peritoneal macrophages with LPS and MALP-2 (10 ug/ml) caused the appearance of similar concentrations of bioactive cytokines in the supernatants from cells of both rat strains. These results demonstrate that TLR2 is essential for the manifestation of MALP-2, but not LPS-induced inflammatory responses. A moderate participation of CD36 in MALP-2-induced sickness- and cytokine-responses can not be ruled out but is unlikely as LPS-induced inflammatory responses were also attenuated in SHR. PMID- 22042913 TI - Proactive strategies to avoid infectious disease. AB - Infectious disease exerts a large selective pressure on all organisms. One response to this has been for animals to evolve energetically costly immune systems to counter infection, while another--the focus of this theme issue--has been the evolution of proactive strategies primarily to avoid infection. These strategies can be grouped into three types, all of which demonstrate varying levels of interaction with the immune system. The first concerns maternal strategies that function to promote the immunocompetence of their offspring. The second type of strategy influences mate selection, guiding the selection of a healthy mate and one who differs maximally from the self in their complement of antigen-coding genes. The third strategy involves two classes of behaviour. One relates to the capacity of the organisms to learn associations between cues indicative of pathogen threat and immune responses. The other relates to prevention and even treatment of infection through behaviours such as avoidance, grooming, quarantine, medicine and care of the sick. In humans, disease avoidance is based upon cognition and especially the emotion of disgust. Human disease avoidance is not without its costs. There is a propensity to reject healthy individuals who just appear sick--stigmatization--and the system may malfunction, resulting in various forms of psychopathology. Pathogen threat also appears to have been a highly significant and unrecognized force in shaping human culture so as to minimize infection threats. This cultural shaping process--moralization- can be co-opted to promote human health. PMID- 22042914 TI - Infection before pregnancy affects immunity and response to social challenge in the next generation. AB - Natural selection should favour parents that are able to adjust their offspring's life-history strategy and resource allocation in response to changing environmental and social conditions. Pathogens impose particularly strong and variable selective pressure on host life histories, and parental genes will benefit if offspring are appropriately primed to meet the immunological challenges ahead. Here, we investigated transgenerational immune priming by examining reproductive resource allocation by female mice in response to direct infection with Babesia microti prior to pregnancy. Female mice previously infected with B. microti gained more weight over pregnancy, and spent more time nursing their offspring. These offspring generated an accelerated response to B. microti as adults, clearing the infection sooner and losing less weight as a result of infection. They also showed an altered hormonal response to novel social environments, decreasing instead of increasing testosterone production upon social housing. These results suggest that a dominance-resistance trade-off can be mediated by cues from the previous generation. We suggest that strategic maternal investment in response to an infection leads to increased disease resistance in the following generation. Offspring from previously infected mothers downregulate investment in acquisition of social dominance, which in natural systems would reduce access to mating opportunities. In doing so, however, they avoid the reduced disease resistance associated with increased testosterone and dominance. The benefits of accelerated clearance of infection and reduced weight loss during infection may outweigh costs associated with reduced social dominance in an environment where the risk of disease is high. PMID- 22042915 TI - Mate preferences and infectious disease: theoretical considerations and evidence in humans. AB - Mate preferences may operate in part to mitigate the threats posed by infectious disease. In this paper, we outline various ways in which preferring healthy mates can offer direct benefits in terms of pathogen avoidance and indirect benefits in terms of heritable immunity to offspring, as well as the costs that may constrain mate preferences for health. We then pay special attention to empirical work on mate preferences in humans given the depth and breadth of research on human mating. We review this literature and comment on the degree to which human mate preferences may reflect preferences for health. PMID- 22042917 TI - Behavioural defences in animals against pathogens and parasites: parallels with the pillars of medicine in humans. AB - No other theme in animal biology seems to be more central than the concept of employing strategies to survive and successfully reproduce. In nature, controlling or avoiding pathogens and parasites is an essential fitness strategy because of the ever-present disease-causing organisms. The disease-control strategies discussed here are: physical avoidance and removal of pathogens and parasites; quarantine or peripheralization of conspecifics that could be carrying potential pathogens; herbal medicine, animal style, to prevent or treat an infection; potentiation of the immune system; and care of sick or injured group members. These strategies are seen as also encompassing the pillars of human medicine: (i) quarantine; (ii) immune-boosting vaccinations; (iii) use of medicinal products; and (iv) caring or nursing. In contrast to animals, in humans, the disease-control strategies have been consolidated into a consistent and extensive medical system. A hypothesis that explains some of this difference between animals and humans is that humans are sick more often than animals. This increase in sickness in humans leading to an extensive, cognitively driven medical system is attributed to an evolutionary dietary transition from mostly natural vegetation to a meat-based diet, with an increase in health-eroding free radicals and a dietary reduction of free-radical-scavenging antioxidants. PMID- 22042918 TI - The behavioural immune system and the psychology of human sociality. AB - Because immunological defence against pathogens is costly and merely reactive, human anti-pathogen defence is also characterized by proactive behavioural mechanisms that inhibit contact with pathogens in the first place. This behavioural immune system comprises psychological processes that infer infection risk from perceptual cues, and that respond to these perceptual cues through the activation of aversive emotions, cognitions and behavioural impulses. These processes are engaged flexibly, producing context-contingent variation in the nature and magnitude of aversive responses. These processes have important implications for human social cognition and social behaviour-including implications for social gregariousness, person perception, intergroup prejudice, mate preferences, sexual behaviour and conformity. Empirical evidence bearing on these many implications is reviewed and discussed. This review also identifies important directions for future research on the human behavioural immune system- including the need for enquiry into underlying mechanisms, additional behavioural consequences and implications for human health and well-being. PMID- 22042919 TI - Contamination sensitivity and the development of disease-avoidant behaviour. AB - Owing to their developing cognitive abilities and their limited knowledge about the biological basis of illness, children often have less expertise at disease avoidance than adults. However, affective reactions to contaminants through the acquisition of disgust and the social and cultural transmissions of knowledge about contamination and contagion provide impetus for children to learn effective disease-avoidant behaviours early in their development. In this article, we review the ontogenetic development of knowledge about contamination and contagion with particular attention to the role of socialization and culture. Together with their emerging cognitive abilities and affective reactions to contaminants, informal and formal cultural learning shape children's knowledge about disease. Through this process, the perceptual cues of contamination are linked to threats of disease outcomes and can act as determinants of disease-avoidant behaviours. PMID- 22042916 TI - Brain-immune interactions and the neural basis of disease-avoidant ingestive behaviour. AB - Neuro-immune interactions are widely manifested in animal physiology. Since immunity competes for energy with other physiological functions, it is subject to a circadian trade-off between other energy-demanding processes, such as neural activity, locomotion and thermoregulation. When immunity is challenged, this trade-off is tilted to an adaptive energy protecting and reallocation strategy that is identified as 'sickness behaviour'. We review diverse disease-avoidant behaviours in the context of ingestion, indicating that several adaptive advantages have been acquired by animals (including humans) during phylogenetic evolution and by ontogenetic experiences: (i) preventing waste of energy by reducing appetite and consequently foraging/hunting (illness anorexia), (ii) avoiding unnecessary danger by promoting safe environments (preventing disease encounter by olfactory cues and illness potentiation neophobia), (iii) help fighting against pathogenic threats (hyperthermia/somnolence), and (iv) by associative learning evading specific foods or environments signalling danger (conditioned taste avoidance/aversion) and/or at the same time preparing the body to counteract by anticipatory immune responses (conditioning immunomodulation). The neurobiology behind disease-avoidant ingestive behaviours is reviewed with special emphasis on the body energy balance (intake versus expenditure) and an evolutionary psychology perspective. PMID- 22042920 TI - Disease avoidance as a functional basis for stigmatization. AB - Stigmatization is characterized by chronic social and physical avoidance of a person(s) by other people. Infectious disease may produce an apparently similar form of isolation-disease avoidance-but on symptom remission this often abates. We propose that many forms of stigmatization reflect the activation of this disease-avoidance system, which is prone to respond to visible signs and labels that connote disease, irrespective of their accuracy. A model of this system is presented, which includes an emotional component, whereby visible disease cues directly activate disgust and contamination, motivating avoidance, and a cognitive component, whereby disease labels bring to mind disease cues, indirectly activating disgust and contamination. The unique predictions of this model are then examined, notably that people who are stigmatized evoke disgust and are contaminating. That animals too show avoidance of diseased conspecifics, and that disease-related stigma targets are avoided in most cultures, also supports this evolutionary account. The more general implications of this approach are then examined, notably how it can be used to good (e.g. improving hygiene) or bad (e.g. racial vilification) ends, by yoking particular labels with cues that connote disease and disgust. This broadening of the model allows for stigmatization of groups with little apparent connection to disease. PMID- 22042921 TI - Disgust: the disease-avoidance emotion and its dysfunctions. AB - This review analyses the accumulating evidence from psychological, psychophysiological, neurobiological and cognitive studies suggesting that the disease-avoidance emotion of disgust is a predominant emotion experienced in a number of psychopathologies. Current evidence suggests that disgust is significantly related to small animal phobias (particularly spider phobia), blood injection-injury phobia and obsessive-compulsive disorder contamination fears, and these are all disorders that have primary disgust elicitors as a significant component of their psychopathology. Disgust propensity and sensitivity are also significantly associated with measures of a number of other psychopathologies, including eating disorders, sexual dysfunctions, hypochondriasis, height phobia, claustrophobia, separation anxiety, agoraphobia and symptoms of schizophrenia- even though many of these psychopathologies do not share the disease-avoidance functionality that characterizes disgust. There is accumulating evidence that disgust does represent an important vulnerability factor for many of these psychopathologies, but when disgust-relevant psychopathologies do meet the criteria required for clinical diagnosis, they are characterized by significant levels of both disgust and fear/anxiety. Finally, it has been argued that disgust may also facilitate anxiety and distress across a broad range of psychopathologies through its involvement in more complex human emotions such as shame and guilt, and through its effect as a negative affect emotion generating threat-interpretation biases. PMID- 22042922 TI - Parasite stress promotes homicide and child maltreatment. AB - Researchers using the parasite-stress theory of human values have discovered many cross-cultural behavioural patterns that inform a range of scholarly disciplines. Here, we apply the theory to major categories of interpersonal violence, and the empirical findings are supportive. We hypothesize that the collectivism evoked by high parasite stress is a cause of adult-on-adult interpersonal violence. Across the US states, parasite stress and collectivism each positively predicts rates of men's and women's slaying of a romantic partner, as well as the rate of male honour homicide and of the motivationally similar felony-related homicide. Of these four types of homicide, wealth inequality has an independent effect only on rates of male-honour and felony-related homicide. Parasite stress and collectivism also positively predict cross-national homicide rates. Child maltreatment by caretakers is caused, in part, by divestment in offspring of low phenotypic quality, and high parasite stress produces more such offspring than low parasite stress. Rates of each of two categories of the child maltreatment- lethal and non-lethal--across the US states are predicted positively by parasite stress, with wealth inequality and collectivism having limited effects. Parasite stress may be the strongest predictor of interpersonal violence to date. PMID- 22042923 TI - Why disgust matters. AB - The new synthesis about disgust is that it is a system that evolved to motivate infectious disease avoidance. There are vital practical and intellectual reasons why we need to understand disgust better. Practically, disgust can be harnessed to combat the behavioural causes of infectious and chronic disease such as diarrhoeal disease, pandemic flu and smoking. Disgust is also a source of much human suffering; it plays an underappreciated role in anxieties and phobias such as obsessive compulsive disorder, social phobia and post-traumatic stress syndromes; it is a hidden cost of many occupations such as caring for the sick and dealing with wastes, and self-directed disgust afflicts the lives of many, such as the obese and fistula patients. Disgust is used and abused in society, being both a force for social cohesion and a cause of prejudice and stigmatization of out-groups. This paper argues that a better understanding of disgust, using the new synthesis, offers practical lessons that can enhance human flourishing. Disgust also provides a model system for the study of emotion, one of the most important issues facing the brain and behavioural sciences today. PMID- 22042924 TI - Stopping a killer: improving the diagnosis, treatment, and prevention of acute ascending aortic dissections. PMID- 22042925 TI - Ineffective therapy, underpowered studies, or merely too little, too late? Risk factors and impact of maternal corticosteroid treatment on outcome in antibody associated fetal heart block. PMID- 22042926 TI - Circulating MicroRNAs in cardiovascular disease. PMID- 22042928 TI - Unilateral pulmonary edema secondary to mitral valve perforation. PMID- 22042927 TI - Atrial fibrillation: current knowledge and future directions in epidemiology and genomics. PMID- 22042929 TI - Cardiology Patient Page. Takotsubo (stress) cardiomyopathy. PMID- 22042930 TI - Immunosuppression and the abdominal aortic aneurysm: Doctor Jekyll or Mister Hyde? PMID- 22042931 TI - Aldosterone, mineralocorticoid receptor activation, and cardiovascular remodeling. PMID- 22042933 TI - Letter by Raposeiras-Roubin et al regarding article, "mortality associated with atrial fibrillation in patients with myocardial infarction: a systematic review and meta-analysis". PMID- 22042934 TI - Letter by Angelini et al regarding article, "incidence of sudden cardiac death in the national collegiate athletic association". PMID- 22042935 TI - Is there an ideal way to combine trastuzumab with chemotherapy? PMID- 22042936 TI - Personalizing locoregional treatment in the adjuvant setting of early breast cancer on the basis of molecular background: an exciting enigma. PMID- 22042937 TI - Palliative treatment: anticancer, antisymptom, or end-of-life care? PMID- 22042938 TI - Breast conservation versus mastectomy in triple-negative breast cancer: two steps forward, one step back? PMID- 22042939 TI - Polymicrobial feculent meningitis with detection of Slackia exigua in the cerebrospinal fluid of a patient with advanced rectal carcinoma. PMID- 22042940 TI - Risk-adapted treatment in clinical stage I testicular seminoma: the third Spanish Germ Cell Cancer Group study. AB - PURPOSE: To confirm the efficacy of a risk-adapted treatment approach for patients with clinical stage I seminoma. The aim was to reduce both the risk of relapse and the proportion of patients receiving adjuvant chemotherapy while maintaining a high cure rate. PATIENTS AND METHODS: From 2004 to 2008, 227 patients were included after orchiectomy in a multicenter study. Eighty-four patients (37%) presented no local risk factors, 44 patients (19%) had tumors larger than 4 cm, 25 patients (11%) had rete testis involvement, and 74 patients (33%) had both criteria. Only the latter group received two courses of adjuvant carboplatin, whereas the rest were managed by surveillance. RESULTS: After a median follow-up time of 34 months, 16 relapses (7%) have been documented (15 [9.8%] among patients on surveillance and one [1.4%] among those treated with carboplatin). All relapses occurred in retroperitoneal lymph nodes, except for one case in pelvic nodes. Median node size was 25 mm, and median time to recurrence was 14 months. All patients were rendered disease-free with chemotherapy. The actuarial 3-year disease-free survival rate was 88.1% (95% CI, 82.3% to 93.9%) for patients on surveillance and 98.0% (95% CI, 94.0% to 100%) for those treated with adjuvant chemotherapy. Overall 3-year survival was 100%. CONCLUSION: With the limitations of the short follow-up duration, we confirm that a risk-adapted approach is effective for stage I seminoma. Adjuvant carboplatin seems adequate treatment for patients with 2 risk criteria, as is active surveillance for those with 0 to one risk factors. More reliable predictive factors are needed to improve the applicability of this model. PMID- 22042941 TI - Rare phenomenon of extracranial metastasis of glioblastoma. PMID- 22042942 TI - Positive sentinel nodes without axillary dissection: implications for the radiation oncologist. PMID- 22042943 TI - Tumor lysis syndrome and acquired ichthyosis occurring after chemotherapy for lung adenocarcinoma. PMID- 22042944 TI - Primary follicular dendritic cell sarcoma of liver treated with cyclophosphamide, doxorubicin, vincristine, and prednisone regimen and surgery. PMID- 22042945 TI - Use of zidovudine and interferon alfa with chemotherapy improves survival in both acute and lymphoma subtypes of adult T-cell leukemia/lymphoma. AB - PURPOSE: Adult T-cell leukemia/lymphoma (ATLL) is a mature (post-thymic) T-cell lymphoma associated with human T-lymphotropic virus type 1 infection. Survival in aggressive subtypes remains poor, and treatment resistance is frequent. Use of zidovudine (ZDV) and interferon alfa (IFN-alpha) has been associated with improved response rates in small studies and prolonged overall survival in leukemic ATLL subtypes in a recent meta-analysis. PATIENTS AND METHODS: We report the clinicopathologic characteristics, treatment, and outcome of 73 patients with aggressive ATLL (acute ATLL, 29; lymphoma ATLL, 44) diagnosed and treated in England between 1999 and 2009. The impact of ZDV/IFN-alpha on treatment response and survival was assessed. RESULTS: The overall response rate ranged from 49% with chemotherapy alone to 81% with combined first-line therapy (chemotherapy with concurrent/sequential ZDV/IFN-alpha). Median overall survival (OS) was 9 months: 7.5 months for acute ATLL and 10 months for lymphoma ATLL. Use of ZDV/IFN alpha at any time prolonged survival in acute (P < .001) and lymphoma ATLL (P < .001) and was the sole factor associated with reduction in risk of death in aggressive ATLL (hazard ratio, 0.23; 95% CI, 0.09 to 0.60; P = .002). Combined first-line therapy prolonged median OS in acute (P = .0081) and lymphoma ATLL (P = .001) compared with chemotherapy alone. CONCLUSION: These data support the use of low-dose ZDV/IFN-alpha with chemotherapy in first-line treatment of acute and lymphoma ATLL. PMID- 22042946 TI - Disease-related outcomes with long-term follow-up: an updated analysis of the intergroup exemestane study. AB - PURPOSE: Intergroup Exemestane Study (IES), an investigator-led study in 4,724 postmenopausal patients with early-stage breast cancer has demonstrated clinically important benefits from switching adjuvant endocrine therapy after 2 to 3 years of tamoxifen to exemestane. Now, with longer follow-up, a large number of non-breast cancer-related events have been reported. Exploratory analyses describe breast cancer-free survival (BCFS) and explore incidence and patterns of the different competing events. PATIENTS AND METHODS: Patients who were disease free after 2 to 3 years of adjuvant tamoxifen were randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years of adjuvant endocrine therapy. At this planned analysis, the median follow-up was 91 months. Principal analysis focuses on 4,052 patients with estrogen receptor (ER) -positive and 547 with ER-unknown tumors. RESULTS: In all, 930 BCFS events have been reported (exemestane, 423; tamoxifen, 507), giving an unadjusted hazard ratio (HR) of 0.81 (95% CI, 0.71 to 0.92; P = .001) in favor of exemestane in the ER-positive/ER unknown group. Analysis partitioned at 2.5 years after random assignment showed that the on-treatment benefit of switching to exemestane (HR, 0.60; 95% CI, 0.48 to 0.75; P < .001) was not lost post-treatment, but that there was no additional gain once treatment had ceased (HR, 0.94; 95% CI, 0.80 to 1.10; P = .60). Improvement in overall survival was demonstrated, with 352 deaths in the exemestane group versus 405 deaths in the tamoxifen group (HR, 0.86; 95% CI, 0.75 to 0.99; P = .04). Of these, 222 were reported as intercurrent deaths (exemestane, 107; tamoxifen, 115). CONCLUSION: The protective effect of switching to exemestane compared with continuing on tamoxifen on risk of relapse or death was maintained for at least 5 years post-treatment and was associated with a continuing beneficial impact on overall survival. PMID- 22042948 TI - Prognostic or predictive? It's time to get back to definitions! PMID- 22042947 TI - MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. AB - PURPOSE: Amplification of the MET proto-oncogene in gastroesophageal cancer (GEC) may constitute a molecular marker for targeted therapy. We examined a GEC cohort with follow-up and reported the clinical response of four additional patients with MET-amplified tumors to the small molecule inhibitor crizotinib as part of an expanded phase I cohort study. PATIENTS AND METHODS: From 2007 to 2009, patients with GEC were genetically screened as a consecutive series of 489 tumors (stages 0, I, and II, 39%; III, 25%; IV, 36%; n = 222 esophageal, including n = 21 squamous carcinomas). MET, EGFR, and HER2 amplification status was assessed by using fluorescence in situ hybridization. RESULTS: Ten (2%) of 489 patients screened harbored MET amplification; 23 (4.7%) harbored EGFR amplification; 45 (8.9%) harbored HER2 amplification; and 411 (84%) were wild type for all three genes (ie, negative). MET-amplified tumors were typically high-grade adenocarcinomas that presented at advanced stages (5%; n = 4 of 80). EGFR amplified tumors showed the highest fraction of squamous cell carcinoma (17%; n = 4 of 23). HER2, MET, and EGFR amplification were, with one exception (MET and EGFR positive), mutually exclusive events. Survival analysis in patients with stages III and IV disease showed substantially shorter median survival in MET/EGFR-amplified groups, with a rank order for all groups by median survival (from most to least aggressive): MET (7.1 months; P < .001) less than EGFR (11.2 months; P = .16) less than HER2 (16.9 months; P = .89) when compared with the negative group (16.2 months). Two of four patients with MET-amplified tumors treated with crizotinib experienced tumor shrinkage (-30% and -16%) and experienced progression after 3.7 and 3.5 months. CONCLUSION: MET amplification defines a small and aggressive subset of GEC with indications of transient sensitivity to the targeted MET inhibitor crizotinib (PF-02341066). PMID- 22042949 TI - Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. AB - PURPOSE: Growth hormone deficiency (GHD) after radiation therapy negatively affects growth and development and quality of life in children with brain tumors. PATIENTS AND MATERIALS: Between 1997 and 2008, 192 pediatric patients with localized primary brain tumors (ependymoma, n = 88; low-grade glioma, n = 51; craniopharyngioma, n = 28; high-grade glioma, n = 23; and other tumor types, n = 2) underwent provocative testing of GH secretion by using the secretogogues arginine and L-dopa before and after (6, 12, 36, and 60 months) conformal radiation therapy (CRT). A total of 664 arginine/l-dopa test procedures were performed. RESULTS: Baseline testing revealed preirradiation GHD in 22.9% of tested patients. On the basis of data from 118 patients, peak GH was modeled as an exponential function of time after CRT and mean radiation dose to the hypothalamus. The average patient was predicted to develop GHD with the following combinations of the time after CRT and mean dose to the hypothalamus: 12 months and more than 60 Gy; 36 months and 25 to 30 Gy; and 60 months and 15 to 20 Gy. A cumulative dose of 16.1 Gy to the hypothalamus would be considered the mean radiation dose required to achieve a 50% risk of GHD at 5 years (TD(50/5)). CONCLUSION: GH secretion after CRT can be predicted on the basis of dose and time after irradiation in pediatric patients with localized brain tumors. These findings provide an objective radiation dose constraint for the hypothalamus. PMID- 22042950 TI - Breast cancer risk for noncarriers of family-specific BRCA1 and BRCA2 mutations: findings from the Breast Cancer Family Registry. AB - PURPOSE: Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs). PATIENTS AND METHODS: Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors. RESULTS: We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases. CONCLUSION: These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation. PMID- 22042951 TI - Donor-derived lymphomatoid papulosis in a stem-cell transplantation recipient. PMID- 22042952 TI - Duration of short-course androgen suppression therapy and the risk of death as a result of prostate cancer. AB - PURPOSE: We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories. PATIENTS AND METHODS: Between February 2, 1996, and December 27, 2001, 761 men with unfavorable-risk PC were treated in Australia, New Zealand, Ireland, or the United States in a randomized trial with radiotherapy and 3, 4, or 6 months of AST (the study cohort). Competing risks regression was used to evaluate whether the duration of AST interacted with GS and was significantly associated with the risk of PCSM, adjusting for age, trial site, and PC prognostic factors. RESULTS: After a median follow-up of 10.9 years, 263 men died, 111 (42%) from PC. For all men, 6 versus 3 or 4 months of AST was associated with a reduced risk of PCSM (adjusted hazard ratio [AHR], 0.55; 95% CI, 0.36 to 0.82; P = .004). AHRs evaluating the impact of the duration of AST on the risk of PCSM were 0.67 (95% CI, 0.29 to 1.56; P = .35), 0.47 (95% CI, 0.25 to 0.85; P = .01), and 0.59 (95% CI, 0.30 to 1.19; P = .14) for men with GS <= 6, 7, and 8 to 10 PC, respectively. Therefore, the strongest evidence for this benefit was in men with GS 7 PC. CONCLUSION: AST durations of no less than 6 months should be considered when treating GS 7 PC with conventional dose RT. PMID- 22042953 TI - Idiotype vaccination as consolidation therapy: time for integration into standard of care for follicular lymphoma? PMID- 22042954 TI - Genetic activation of the MET pathway and prognosis of patients with high-risk, radically resected gastric cancer. AB - PURPOSE: To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain (CNG) or an activating truncation within a deoxyadenosine tract element (DATE) in the promoter region of the MET ligand HGF. PATIENTS AND METHODS: A single-institution cohort of 230 patients with stage II/III gastric cancer was studied. Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction. Quantitative polymerase chain reaction (qPCR) for MET CNG and sequencing for HGF DATE truncation (< 25 deoxyadenosines instead of 30) were used. Results were analyzed for association with disease-free survival (DFS) and overall survival (OS). To assess the reliability of the qPCR measurement, a random sample of cases was reanalyzed using an alternative assay (fluorescent in situ hybridization [FISH]) with calculation of the intracorrelation coefficient (ICC). RESULTS: In 216 assessable patients, MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients (10%) and 30 patients (13%), respectively. Patients with MET CNG five or more copies (MET-positive) showed significantly worse prognosis with multivariate hazard ratio (HR) of 3.02 (95% CI, 1.71 to 5.33; P < .001) for DFS and multivariate HR of 2.91 (95% CI, 1.65 to 5.11; P < .001) for OS. The agreement between qPCR and FISH was high, with ICC = 0.9% (95% CI, 0.81% to 0.95%; the closer the ICC is to 1, the greater is the agreement). HGF-truncated DATE did not show relevant prognostic effect. CONCLUSION: In this study, qPCR revealed approximately 10% of white patients with gastric cancer harboring MET CNG of five or more copies. This marker was significantly associated with unfavorable prognosis. This information is relevant to the current clinical development of anti-MET compounds. PMID- 22042956 TI - Do women remain at risk even if they do not inherit a familial BRCA1/2 mutation? PMID- 22042955 TI - Cancer immunotherapy comes of age. AB - Cancer immunotherapy comprises a variety of treatment approaches, incorporating the tremendous specificity of the adaptive immune system (T cells and antibodies) as well as the diverse and potent cytotoxic weaponry of both adaptive and innate immunity. Immunotherapy strategies include antitumor monoclonal antibodies, cancer vaccines, adoptive transfer of ex vivo activated T and natural killer cells, and administration of antibodies or recombinant proteins that either costimulate immune cells or block immune inhibitory pathways (so-called immune checkpoints). Although clear clinical efficacy has been demonstrated with antitumor antibodies since the late 1990s, other immunotherapies had not been shown to be effective until recently, when a spate of successes established the broad potential of this therapeutic modality. These successes are based on fundamental scientific advances demonstrating the toleragenic nature of cancer and the pivotal role of the tumor immune microenvironment in suppressing antitumor immunity. New therapies based on a sophisticated knowledge of immune suppressive cells, soluble factors, and signaling pathways are designed to break tolerance and reactivate antitumor immunity to induce potent, long-lasting responses. Preclinical models indicate the importance of a complex integrated immune response in eliminating established tumors and validate the exploration of combinatorial treatment regimens, which are anticipated to be far more effective than monotherapies. Unlike conventional cancer therapies, most immunotherapies are active and dynamic, capable of inducing immune memory to propagate a successful rebalancing of the equilibrium between tumor and host. PMID- 22042957 TI - DNMT3A mutations in acute myeloid leukemia: impact on low-risk patients with CEBPA mutations. PMID- 22042958 TI - Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. AB - PURPOSE: NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2-positive breast cancer. PATIENTS AND METHODS: Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). RESULTS: Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. CONCLUSION: DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen. PMID- 22042959 TI - Evaluating survivorship care plans: results of a randomized, clinical trial of patients with breast cancer. AB - PURPOSE: An Institute of Medicine report recommends that patients with cancer receive a survivorship care plan (SCP). The trial objective was to determine if an SCP for breast cancer survivors improves patient-reported outcomes. PATIENTS AND METHODS: Women with early-stage breast cancer who completed primary treatment at least 3 months previously were eligible. Consenting patients were allocated within two strata: less than 24 months and >= 24 months since diagnosis. All patients were transferred to their own primary care physician (PCP) for follow up. In addition to a discharge visit, the intervention group received an SCP, which was reviewed during a 30-minute educational session with a nurse, and their PCP received the SCP and guideline on follow-up. The primary outcome was cancer related distress at 12 months, assessed by the Impact of Event Scale (IES). Secondary outcomes included quality of life, patient satisfaction, continuity/coordination of care, and health service measures. RESULTS: Overall, 408 survivors were enrolled through nine tertiary cancer centers. There were no differences between groups on cancer-related distress or on any of the patient reported secondary outcomes, and there were no differences when the two strata were analyzed separately. More patients in the intervention than control group correctly identify their PCP as primarily responsible for follow-up (98.7% v 89.1%; difference, 9.6%; 95% CI, 3.9 to 15.9; P = .005). CONCLUSION: The results do not support the hypothesis that SCPs are beneficial for improving patient reported outcomes. Transferring follow-up to PCPs is considered an important strategy to meet the demand for scarce oncology resources. SCPs were no better than a standard discharge visit with the oncologist to facilitate transfer. PMID- 22042960 TI - CYP2D6 and tamoxifen: awaiting the denouement. PMID- 22042961 TI - Is it time for (survivorship care) plan B? PMID- 22042962 TI - Therapy for pediatric brain tumors and the risk of growth hormone deficiency. PMID- 22042963 TI - Large-cell neuroendocrine carcinoma of the lung harboring EGFR mutation and responding to gefitinib. PMID- 22042964 TI - Ectopic choriocarcinoma masquerading as a persisting pregnancy of unknown location: case report and review of the literature. PMID- 22042965 TI - Survival is not a good outcome for randomized trials with effective subsequent therapies. PMID- 22042966 TI - MET signaling pathway: a rational target for cancer therapy. PMID- 22042967 TI - Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. AB - PURPOSE: The interim analysis of the National Cancer Institute of Canada Clinical Trials Group MA.17 trial showed that letrozole was significantly better than placebo in disease-free survival (DFS) for postmenopausal women with hormone receptor-positive breast cancer following about 5 years of tamoxifen therapy. When patients were unblinded, those on placebo were offered letrozole. Longer term efficacy of letrozole, especially survival, was of particular interest because the median follow-up of the first interim analysis was only 2.5 years. Efficacy was difficult to assess because more than 60% of placebo patients crossed over to letrozole after being unblinded. PATIENTS AND METHODS: Two statistical approaches were used to adjust for the potential effects of treatment crossover: one was based on the inverse probability of censoring weighted (IPCW) Cox model and the other on a Cox model with time-dependent covariates. RESULTS: With a median follow-up of 64 months, the hazard ratios (HRs) of letrozole and placebo from the IPCW analyses were HR of 0.52 (95% CI, 0.45 to 0.61; P < .001) for DFS, HR of 0.51 (95% CI, 0.42 to 0.61; P < .001) for distant disease-free survival (DDFS), and HR of 0.61 (95% CI, 0.52 to 0.71; P < .001) for overall survival (OS). The results from the analyses based on the Cox model with time dependent covariates were similar for letrozole and placebo: HR of 0.58 (95% CI, 0.47 to 0.72; P < .001) for DFS, HR of 0.68 (95% CI, 0.52 to 0.88; P = .004) for DDFS, and HR of 0.76 (95% CI, 0.60 to 0.96; P = .02) for OS. CONCLUSION: Exploratory analyses based on longer follow-up and adjusting for treatment crossover suggest that extended adjuvant letrozole was superior to placebo in DFS, DDFS, and OS. PMID- 22042968 TI - Alpha particle and proton relative thermoluminescence efficiencies in LiF:Mg,Cu,P:is track structure theory up to the task? AB - Low-energy alpha particle and proton heavy charged particle (HCP) relative thermoluminescence (TL) efficiencies are calculated for the major dosimetric glow peak in LiF:Mg,Cu,P (MCP-N) in the framework of track structure theory (TST). The calculations employ previously published TRIPOS-E Monte Carlo track segment values of the radial dose in condensed phase LiF calculated at the Instituto National de Investigaciones Nucleares (Mexico) and experimentally measured normalised (60)Co gamma-induced TL dose-response functions, f(D), carried out at the Institute of Nuclear Physics (Poland). The motivation for the calculations is to test the validity of TST in a TL system in which f(D) is not supralinear (f(D) >1) and is not significantly dependent on photon energy contrary to the behaviour of the dose-response of composite peak 5 in the glow curve of LiF:Mg,Ti (TLD 100). The calculated HCP relative efficiencies in LiF:MCP-N are 23-87% lower than the experimentally measured values, indicating a weakness in the major premise of TST which exclusively relates HCP effects to the radiation action of the secondary electrons liberated by the HCP slowing down. However, an analysis of the uncertainties involved in the TST calculations and experiments (i.e. experimental measurement of f(D) at high levels of dose, sample light self absorption and accuracy in the estimation of D(r), especially towards the end of the HCP track) indicate that these may be too large to enable a definite conclusion. More accurate estimation of sample light self-absorption, improved measurements of f(D) and full-track Monte Carlo calculations of D(r) incorporating improvements of the low-energy electron transport are indicated in order to reduce uncertainties and enable a final conclusion. PMID- 22042969 TI - Estimation of beta-ray skin dose from exposure to fission fallout from the Hiroshima atomic bomb. AB - Beta-ray skin dose due to the fission fallout from the Hiroshima atomic bomb is potentially related to the epilation in the black rain area. The absorbed dose to the skin from beta-rays emitted by fission fallout has been estimated for an initial 137Cs deposition of 1 kBq m-2 on the ground at 0.5 h after the explosion. The estimated skin dose takes into account both external exposure from fission fallout radionuclides uniformly distributed in 1 mm of soil on the surface of the ground and from a 26 MUm thickness of contaminated soil on the skin, using the Monte Carlo radiation transport code MCNP-4C. The cumulative skin dose for 1 month after the explosion is taken as the representative value. The estimated skin dose for an initial 137Cs deposition of 1 kBq m-2 was determined to be about 500 mSv. PMID- 22042971 TI - MicroRNA-494 downregulates KIT and inhibits gastrointestinal stromal tumor cell proliferation. AB - PURPOSE: Gain-of-function mutations and KIT overexpression are well-known tumorigenesis mechanisms in gastrointestinal stromal tumors (GIST). This study aimed to discover microRNAs (miRNA) that target KIT and reveal the relationship between the discovered miRNAs and KIT expression in GISTs. EXPERIMENTAL DESIGN: Fresh-frozen GISTs from 31 patients were used to confirm the relationship between miR-494 and KIT expression using quantitative reverse transcription-PCR to assess miR-494 expression levels and Western blotting to assess KIT protein expression levels. A luciferase assay was conducted for the target evaluation. The functional effects of miR-494 on GIST882 cells (GIST cell line with activating KIT mutation) were validated by a cell proliferation assay and fluoresce activated cell sorting analysis. RESULTS: An inverse relationship was found between the expression levels of miR-494 and KIT in GISTs (r = -0.490, P = 0.005). The direct targeting of KIT by miR-494 was shown by the reduction in KIT expression after miR-494 overexpression and the increase in KIT expression after inhibiting endogenous miR-494 expression. We showed that miR-494 regulates KIT by binding two different seed match sites. Induced miR-494 overexpression in GIST882 reduced the expression of downstream molecules in KIT signaling transduction pathways, including phospho-AKT and phospho-STAT3. Finally, miR-494 overexpression provoked apoptosis and inhibited GIST cell growth, which were accompanied by changes in G(1) and S phase content. CONCLUSION: Our findings indicate that miR-494 is a negative regulator of KIT in GISTs and overexpressing miR-494 in GISTs may be a promising approach to GIST treatment. PMID- 22042970 TI - 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido) pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. AB - PURPOSE: We have synthesized and evaluated in vivo 2-(3-{1-carboxy-5-[(6 [(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [(18)F]DCFPyL, as a potential imaging agent for the prostate-specific membrane antigen (PSMA). PSMA is upregulated in prostate cancer epithelia and in the neovasculature of most solid tumors. EXPERIMENTAL DESIGN: [(18)F]DCFPyL was synthesized in two steps from the p-methoxybenzyl (PMB) protected lys-C(O)-glu urea precursor using 6-[(18)F]fluoronicotinic acid tetrafluorophenyl ester ([(18)F]F-Py-TFP) for introduction of (18)F. Radiochemical synthesis was followed by biodistribution and imaging with PET in immunocompromised mice using isogenic PSMA PC3 PIP and PSMA- PC3 flu xenograft models. Human radiation dosimetry estimates were calculated using OLINDA/EXM 1.0. RESULTS: DCFPyL displays a K(i) value of 1.1 +/- 0.1 nmol/L for PSMA. [(18)F]DCFPyL was produced in radiochemical yields of 36%-53% (decay corrected) and specific radioactivities of 340-480 Ci/mmol (12.6-17.8 GBq/MUmol, n = 3). In an immunocompromised mouse model [(18)F]DCFPyL clearly delineated PSMA+ PC3 PIP prostate tumor xenografts on imaging with PET. At 2 hours postinjection, 39.4 +/- 5.4 percent injected dose per gram of tissue (%ID/g) was evident within the PSMA+ PC3 PIP tumor, with a ratio of 358:1 of uptake within PSMA+ PC3 PIP to PSMA- PC3 flu tumor placed in the opposite flank. At or after 1 hour postinjection, minimal nontarget tissue uptake of [(18)F]DCFPyL was observed. The bladder wall is the dose-limiting organ. CONCLUSIONS: These data suggest [(18)F]DCFPyL as a viable, new positron emitting imaging agent for PSMA-expressing tissues. PMID- 22042972 TI - Overexpression of ZEB2 at the invasion front of colorectal cancer is an independent prognostic marker and regulates tumor invasion in vitro. AB - PURPOSE: Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and dissemination. EMT occurs predominantly at the tumor edge where it is induced by cytokines, the extracellular matrix environment, or hypoxia. In the tumor cell, it is further mediated by several transcription factors and microRNAs. The aim of this study was to explore the expression of EMT-associated genes at the invasive front in colorectal cancer and to evaluate their prognostic significance. EXPERIMENTAL DESIGN: We evaluated the expression of 13 EMT associated genes at the invasion front of 30 colorectal liver metastases by quantitative real-time PCR. Immunostaining against zinc finger E-box-binding homeobox 2 (ZEB2) was carried out on 175 primary colorectal cancer specimens and 30 colorectal liver metastases and correlated to clinical and histopathologic data. DLD-1 cells were transfected with siRNA and subjected to migration and invasion assays. RESULTS: Gene expression analysis and immunohistochemistry showed an upregulation of ZEB2 at the invasion front in primary colorectal cancer and liver metastases. Overexpression of ZEB2 at the invasion front correlated significantly with tumor stage in primary colorectal cancer. Moreover, univariate and multivariate analysis revealed overexpression of ZEB2 at the invasion front as an independent prognostic marker for cancer-specific survival. Downregulation of ZEB2 by siRNA decreased the migration and invasion capacity of DLD-1 cells in vitro. CONCLUSIONS: Overexpression of ZEB2 at the invasion front correlates with tumor progression and predicts cancer-specific survival in primary colorectal cancer. Therefore, ZEB2 may be interesting as biomarker and potential target for treatment of colorectal cancer. PMID- 22042973 TI - Genomic and molecular characterization of malignant peripheral nerve sheath tumor identifies the IGF1R pathway as a primary target for treatment. AB - PURPOSE: Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma that lacks effective therapeutic strategies. We gain insight into the most recurrent genetically altered pathways with the purpose of scanning possible therapeutic targets. EXPERIMENTAL DESIGN: We conducted a microarray-based comparative genomic hybridization profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Cancer Hospital. Immunohistochemistry (IHC) and cell biology detection and validation were carried out on human MPNST tissues and cell lines. RESULTS: Genomic characterization of 51 MPNST tissue samples identified several frequently amplified regions harboring 2,599 genes and regions of deletion including 4,901 genes. At the pathway level, we identified a significant enrichment of copy number-altering events in the insulin-like growth factor 1 receptor (IGF1R) pathway, including frequent amplifications of the IGF1R gene itself. To validate the IGF1R pathway as a potential target in MPNSTs, we first confirmed that high IGF1R protein correlated with worse tumor-free survival in an independent set of samples using IHC. Two MPNST cell lines (ST88-14 and STS26T) were used to determine the effect of attenuating IGF1R. Inhibition of IGF1R in ST88-14 cells using siRNAs or an IGF1R inhibitor, MK-0646, led to significant decreases in cell proliferation, invasion, and migration accompanied by attenuation of the PI3K/AKT and mitogen-activated protein kinase pathways. CONCLUSION: These integrated genomic and molecular studies provide evidence that the IGF1R pathway is a potential therapeutic target for patients with MPNST. PMID- 22042974 TI - REG-gamma associates with and modulates the abundance of nuclear activation induced deaminase. AB - Activation-induced deaminase (AID) acts on the immunoglobulin loci in activated B lymphocytes to initiate antibody gene diversification. The abundance of AID in the nucleus appears tightly regulated, with most nuclear AID being either degraded or exported back to the cytoplasm. To gain insight into the mechanisms regulating nuclear AID, we screened for proteins interacting specifically with it. We found that REG-gamma, a protein implicated in ubiquitin- and ATP independent protein degradation, interacts in high stoichiometry with overexpressed nuclear AID as well as with endogenous AID in B cells. REG-gamma deficiency results in increased AID accumulation and increased immunoglobulin class switching. A stable stoichiometric AID-REG-gamma complex can be recapitulated in co-transformed bacteria, and REG-gamma accelerates proteasomal degradation of AID in in vitro assays. Thus, REG-gamma interacts, likely directly, with nuclear AID and modulates the abundance of this antibody diversifying but potentially oncogenic enzyme. PMID- 22042975 TI - Highly potent human hematopoietic stem cells first emerge in the intraembryonic aorta-gonad-mesonephros region. AB - Hematopoietic stem cells (HSCs) emerge during embryogenesis and maintain hematopoiesis in the adult organism. Little is known about the embryonic development of human HSCs. We demonstrate that human HSCs emerge first in the aorta-gonad-mesonephros (AGM) region, specifically in the dorsal aorta, and only later appear in the yolk sac, liver, and placenta. AGM region cells transplanted into immunodeficient mice provide long-term high level multilineage hematopoietic repopulation. Human AGM region HSCs, although present in low numbers, exhibit a very high self-renewal potential. A single HSC derived from the AGM region generates at least 300 daughter HSCs in primary recipients, which disseminate throughout the entire recipient bone marrow and are retransplantable. These findings highlight the vast regenerative potential of the earliest human HSCs and set a new standard for in vitro generation of HSCs from pluripotent stem cells for the purpose of regenerative medicine. PMID- 22042976 TI - Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells. AB - Naive antiviral CD8(+) T cells are activated in the draining LN (DLN) by dendritic cells (DCs) presenting viral antigens. However, many viruses infect LN macrophages, which participate in initiation of innate immunity and B cell activation. To better understand how and why T cells select infected DCs rather than macrophages, we performed intravital microscopy and ex vivo analyses after infecting mice with vaccinia virus (VV), a large DNA virus that infects both LN macrophages and DCs. Although CD8(+) T cells interact with both infected macrophages and DCs in the LN peripheral interfollicular region (PIR), DCs generate more frequent and stable interactions with T cells. VV infection induces rapid release of CCR5-binding chemokines in the LN, and administration of chemokine-neutralizing antibodies diminishes T cell activation by increasing T cell localization to macrophages in the macrophage-rich region (MRR) at the expense of PIR DCs. Similarly, DC ablation increases both T cell localization to the MRR and the duration of T cell-macrophage contacts, resulting in suboptimal T cell activation. Thus, virus-induced chemokines in DLNs enable antiviral CD8(+) T cells to distinguish DCs from macrophages to optimize T cell priming. PMID- 22042979 TI - Clinical quality indicators in laboratory medicine. AB - Clinical laboratories have an important role in improving patient care. The past decades have seen enormous changes with unpredictable improvements in analytical performance, range of tests and capacity to manage large volumes of work. At the same time, there has been a dramatic fall in the rate of laboratory errors. However, there is now a growing awareness that the testing process includes the time before samples reach the laboratory and after reports have been printed and that these areas need to be included in the quality assessment of the total testing process. Laboratory quality should include a focus on patient safety and clinical effectiveness. Services should be patient-centred, timely, efficient and equitable, and finally, should be moulded to ensure optimal outcomes. There is a need to define quality indicators that will ensure there is appropriate choice and selection of tests, use of the appropriate assay standardization and the correct interpretation of the assay results at the appropriate time. These are the areas in which a quality laboratory can, and should, now involve itself. PMID- 22042978 TI - Leaky cell syndrome: a rare cause of pseudohyperkalaemia. AB - Life-threatening situations of hyperkalaemia are often caused by renal failure, hyperglycaemia or medication. However pseudohyperkalaemia, a falsely elevated potassium concentration, is usually caused by haemolysis, repeated clenching of the fist during venepuncture or abnormal cell numbers. Another rare cause of pseudohyperkalaemia is familial pseudohyperkalaemia, an autosomal dominantly inherited trait, with increased leakage of potassium from erythrocytes. Under normal in vivo conditions, this increased leakage is compensated by augmented activity of the Na(+)/K(+) ATPase pump. However, after venepuncture the blood cools down to room temperature, reducing the activity of the Na(+)/K(+) ATPase pump whereby the increased potassium leakage becomes more apparent. Here, we present a Dutch patient with extreme familial pseudohyperkalaemia. Interestingly, his two children also show increased potassium leakage at room temperature, albeit at a lower level. Despite the low prevalence of familial pseudohyperkalaemia, it can have important clinical implications and rapid recognition is desired. PMID- 22042977 TI - Follicular dendritic cells help establish follicle identity and promote B cell retention in germinal centers. AB - Follicular dendritic cells (FDCs) retain and display opsonized antigens in primary follicles and germinal centers (GCs). However, their roles beyond antigen presentation have been incompletely defined. In this study, we tested the impact of selective FDC ablation on short-term follicle and GC function. Within 2 d of FDC ablation, primary follicles lost their homogeneity and became disorganized bands of cells around T zones. These B cell areas retained CXCL13-expressing stromal cells but often exhibited inappropriate ER-TR7 and CCL21 expression. Ablation of GC FDCs led to the disappearance of GCs. When B cell death was prevented using a Bcl2 transgene, FDC ablation led to splenic GC B cell dispersal. Mesenteric lymph node GCs were more resistant but became dispersed when sphingosine-1-phosphate receptor-2 was also removed. These experiments indicate that FDCs help maintain primary follicles as a B cell exclusive niche and define a critical role for FDCs in cell retention within GCs. PMID- 22042980 TI - National guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage. PMID- 22042981 TI - Improvement and validation of 125I-high-performance liquid chromatography method for determination of total human serum choline and ethanolamine plasmalogens. AB - BACKGROUND: Serum plasmalogens (Pls) have gained interest in several clinical symptoms such as metabolic syndrome/atherosclerosis or Alzheimer's disease possibly because of their antioxidant properties. We have developed a highly sensitive and simple method to determine plasmenylcholine (PlsCho; choline plasmalogen) and plasmenylethanolamine (PlsEtn; ethanolamine plasmalogen) separately, using a radioactive iodine and high-performance liquid chromatography ((125)I-HPLC method). The present study reports the improvement and validation of (125)I-HPLC method by introducing a quantitative standard (QS) and online detection with a flow gamma-counter. METHODS: 1-Alkenyl 2,3-cyclic glycerophosphate was prepared as QS from l-alpha-lyso plasmenylcholine by enzymatic treatment with phospholipase D. Online detection with a flow gamma counter was investigated to be available to quantify Pls. The method validation was carried out in terms of selectivity, sensitivity, linearity, precision, accuracy and recovery. RESULTS: Linearity was established over the concentration range 5-300 MUmol/L for Pls and QS with regression coefficients >0.99. The accuracy and reliability were satisfactory. The method has been applied to the determination of human serum Pls from healthy subjects and the elderly with dementia or artery stenoses. CONCLUSIONS: The improved (125)I-HPLC method is useful as an autoanalytical system for a routine diagnostic test of human serum Pls. PMID- 22042982 TI - Effect of ageing and pulmonary inflammation on the incidence and number of cross bridging structures in pneumothorax patients. AB - BACKGROUND: There is an improved prognosis for T4 non-small-cell lung cancer in patients who show particular patterns of direct mediastinal invasion. The particular patterns suggest the presence of direct pathways other than the pulmonary hilum between each of the lungs and the mediastinum/chest wall. PURPOSE: To determine the incidence and number of such direct pathways in pneumothorax patients as well as the factors that affect the development of these pathways. MATERIAL AND METHODS: Two radiologists independently analyzed multidetector computed tomographic images of 81 patients with pneumothorax to assess the incidence and distribution pattern of the cross-bridging structures in the pleural cavity. RESULTS: Cross-bridging structures were observed in the right pneumothorax in 34/54 (63%) patients and in the left pneumothorax in 19/32 (59%) patients. The number of cross-bridging structures was found to be positively correlated with ageing and pulmonary disease. The distribution patterns of cross bridging structures were found to be specific in formation and often in repeated locations, regardless of the presence of pulmonary disease or the age of the patient. CONCLUSION: Cross-bridging structures in pneumothoraces were found more frequently in older patients and in patients with pulmonary disease. However, some of the cross-bridging structures may have been congenital because of their specific formations and repeated locations. PMID- 22042983 TI - Evaluation of cartilage surface injuries using 3D-double echo steady state (3D DESS): effect of changing flip angle from 40 degrees to 90 degrees . AB - BACKGROUND: In magnetic resonance imaging (MRI) with 3D-double-echo steady-state (3D-DESS) sequences, the cartilage-synovial fluid contrast is reported to be better with a flip angle of 90 degrees than with the conventional flip angle of 40 degrees , and the detection rate of knee cartilage injury may be improved. PURPOSE: To compare the diagnostic performance and certainty of diagnosis with 3D DESS images made using two flip angle settings, 40 degrees and 90 degrees , for knee cartilage surface lesions of Grade 2 or above confirmed by arthroscopy. MATERIAL AND METHODS: Images were obtained with 3D-DESS flip angles of 40 degrees and 90 degrees at 1.0T in 13 consecutive patients (2 men, 11 women, age range 18-68 years) evaluated for superficial cartilage injury by arthroscopy. Two radiologists classified the presence or absence of cartilage damage of >=Grade 2 as 'positive (p)' or 'negative (n)', respectively. The rate of agreement with arthroscopic diagnosis was then examined, and the diagnostic performance compared. Diagnostic confidence was assessed scoring the presence or absence of cartilage damage into three categories: 3 = can diagnose with absolute confidence; 2 = can diagnose with a level of certainty as probably present or probably absent; and 1 = cannot make a diagnosis. RESULTS: In a comparison of the rate of agreement between diagnosis by 3D-DESS images and arthroscopy, the rate of agreement was significantly higher and diagnostic performance was better in 90 degrees images for the medial femoral condyle only. Diagnostic confidence was significantly better with 90 degrees flip angle images than with 40 degrees flip angle images for all six cartilage surfaces. CONCLUSION: In evaluating knee cartilage surface lesions with 3D-DESS sequences, a flip angle setting of 90 degrees is more effective than the conventional setting of 40 degrees . PMID- 22042984 TI - Comparison of virtual bronchoscopy with fiberoptic bronchoscopy findings in patients exposed to sulfur mustard gas. AB - BACKGROUND: Fiberoptic bronchoscopy (FB) is the best modality for evaluation of tracheobronchial endoluminal lesions. Virtual bronchoscopy (VB) with the aid of computed tomography (CT) makes it possible to reconstruct endoscopic-like visualization of major airways. Sulfur mustard (SM) used during the Iraq-Iran war affects respiratory tracts and can lead to tracheobronchial stenosis. PURPOSE: To compare VB with FB in SM-exposed patients suspected for airway stenosis. MATERIAL AND METHODS: Thirty-one patients were evaluated with CT and bronchoscopic studies about 15 years after chemical attacks. The median age of patients was 40 years. Spiral CT scans were obtained and data were transferred to a workstation to generate VB images of major airways. Less than one week after CT scan, FB was performed. RESULTS: For the tracheal pathologies seen in FB, the sensitivity, specificity, and accuracy of VB was 90.9%, 95%, and 93.5% for tracheal stenosis, 40%, 96.2%, and 87.1% for vocal cord problems, 100%, 100%, and 100% for postoperative changes, and 100%, 96.7%, and 96.8% for intratracheal nodule. The inflammation of mucosal surface could not be assessed by VB. The bronchial pathologies seen in FB included eight cases of stenosis, and one case of nodule. Sensitivity, specificity, and accuracy of VB for detection of bronchial stenosis was 62.5%, 97.8% and 92.6%, respectively. Overall sensitivity, specificity and accuracy of VB in detecting tracheobronchial stenosis were 78.9%, 97.0%, and 92.9%, respectively. CONCLUSION: Our study indicates that VB is an accurate method for evaluating stenoses, endoluminal nodules, and poststenotic areas within the tracheobronchial tree of SM-exposed victims. This complementary method could be helpful in revealing hidden post-stenotic lesions and also better depict the long tracheal strictures and their actual length. PMID- 22042986 TI - Structural basis for the channel function of a degraded ABC transporter, CFTR (ABCC7). AB - Cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily, but little is known about how this ion channel that harbors an uninterrupted ion permeation pathway evolves from a transporter that works by alternately exposing its substrate conduit to the two sides of the membrane. Here, we assessed reactivity of intracellularly applied thiol-specific probes with cysteine residues substituted into the 12th transmembrane segment (TM12) of CFTR. Our experimental data showing high reaction rates of substituted cysteines toward the probes, strong blocker protection of cysteines against reaction, and reaction-induced alterations in channel conductance support the idea that TM12 of CFTR contributes to the lining of the ion permeation pathway. Together with previous work, these findings raise the possibility that pore-lining elements of CFTR involve structural components resembling those that form the substrate translocation pathway of ABC transporters. In addition, comparison of reaction rates in the open and closed states of the CFTR channel leads us to propose that upon channel opening, the wide cytoplasmic vestibule tightens and the pore-lining TM12 rotates along its helical axis. This simple model for gating conformational changes in the inner pore domain of CFTR argues that the gating transition of CFTR and the transport cycle of ABC proteins share analogous conformational changes. Collectively, our data corroborate the popular hypothesis that degradation of the cytoplasmic-side gate turned an ABC transporter into the CFTR channel. PMID- 22042987 TI - KCNQ1 subdomains involved in KCNE modulation revealed by an invertebrate KCNQ1 orthologue. AB - KCNQ1 channels are voltage-gated potassium channels that are widely expressed in various non-neuronal tissues, such as the heart, pancreas, and intestine. KCNE proteins are known as the auxiliary subunits for KCNQ1 channels. The effects and functions of the different KCNE proteins on KCNQ1 modulation are various; the KCNQ1-KCNE1 ion channel complex produces a slowly activating potassium channel that is crucial for heartbeat regulation, while the KCNE3 protein makes KCNQ1 channels constitutively active, which is important for K(+) and Cl(-) transport in the intestine. The mechanisms by which KCNE proteins modulate KCNQ1 channels have long been studied and discussed; however, it is not well understood how different KCNE proteins exert considerably different effects on KCNQ1 channels. Here, we approached this point by taking advantage of the recently isolated Ci KCNQ1, a KCNQ1 homologue from marine invertebrate Ciona intestinalis. We found that Ci-KCNQ1 alone could be expressed in Xenopus laevis oocytes and produced a voltage-dependent potassium current, but that Ci-KCNQ1 was not properly modulated by KCNE1 and totally unaffected by coexpression of KCNE3. By making chimeras of Ci-KCNQ1 and human KCNQ1, we determined several amino acid residues located in the pore region of human KCNQ1 involved in KCNE1 modulation. Interestingly, though, these amino acid residues of the pore region are not important for KCNE3 modulation, and we subsequently found that the S1 segment plays an important role in making KCNQ1 channels constitutively active by KCNE3. Our findings indicate that different KCNE proteins use different domains of KCNQ1 channels, and that may explain why different KCNE proteins give quite different outcomes by forming a complex with KCNQ1 channels. PMID- 22042988 TI - Influence of pH on Ca2+ current and its control of electrical and Ca2+ signaling in ventricular myocytes. AB - Modulation of L-type Ca(2+) current (I(Ca,L)) by H(+) ions in cardiac myocytes is controversial, with widely discrepant responses reported. The pH sensitivity of I(Ca,L) was investigated (whole cell voltage clamp) while measuring intracellular Ca(2+) (Ca(2+)(i)) or pH(i) (epifluorescence microscopy) in rabbit and guinea pig ventricular myocytes. Selectively reducing extracellular or intracellular pH (pH(o) 6.5 and pH(i) 6.7) had opposite effects on I(Ca,L) gating, shifting the steady-state activation and inactivation curves to the right and left, respectively, along the voltage axis. At low pH(o), this decreased I(Ca,L), whereas at low pH(i), it increased I(Ca,L) at clamp potentials negative to 0 mV, although the current decreased at more positive potentials. When Ca(2+)(i) was buffered with BAPTA, the stimulatory effect of low pH(i) was even more marked, with essentially no inhibition. We conclude that extracellular H(+) ions inhibit whereas intracellular H(+) ions can stimulate I(Ca,L). Low pH(i) and pH(o) effects on I(Ca,L) were additive, tending to cancel when appropriately combined. They persisted after inhibition of calmodulin kinase II (with KN-93). Effects are consistent with H(+) ion screening of fixed negative charge at the sarcolemma, with additional channel block by H(+)(o) and Ca(2+)(i). Action potential duration (APD) was also strongly H(+) sensitive, being shortened by low pH(o), but lengthened by low pH(i), caused mainly by H(+)-induced changes in late Ca(2+) entry through the L-type Ca(2+) channel. Kinetic analyses of pH-sensitive channel gating, when combined with whole cell modeling, successfully predicted the APD changes, plus many of the accompanying changes in Ca(2+) signaling. We conclude that the pH(i)-versus-pH(o) control of I(Ca,L) will exert a major influence on electrical and Ca(2+)-dependent signaling during acid-base disturbances in the heart. PMID- 22042989 TI - Nothing to sneeze at. PMID- 22042990 TI - National plan for clinical guidelines would elevate quality of care, experts say. PMID- 22042991 TI - A qualitative investigation of smoke-free policies on hospital property. AB - BACKGROUND: Many hospitals have adopted smoke-free policies on their property. We examined the consequences of such polices at two Canadian tertiary acute-care hospitals. METHODS: We conducted a qualitative study using ethnographic techniques over a six-month period. Participants (n=186) shared their perspectives on and experiences with tobacco dependence and managing the use of tobacco, as well as their impressions of the smoke-free policy. We interviewed inpatients individually from eight wards (n=82), key policy-makers (n=9) and support staff (n=14) and held 16 focus groups with health care providers and ward staff (n=81). We also reviewed ward documents relating to tobacco dependence and looked at smoking-related activities on hospital property. RESULTS: Noncompliance with the policy and exposure to secondhand smoke were ongoing concerns. Peoples' impressions of the use of tobacco varied, including divergent opinions as to whether such use was a bad habit or an addiction. Treatment for tobacco dependence and the management of symptoms of withdrawal were offered inconsistently. Participants voiced concerns over patient safety and leaving the ward to smoke. INTERPRETATION: Policies mandating smoke-free hospital property have important consequences beyond noncompliance, including concerns over patient safety and disruptions to care. Without adequately available and accessible support for withdrawal from tobacco, patients will continue to face personal risk when they leave hospital property to smoke. PMID- 22042992 TI - Early hormone replacement therapy may yield benefits, researchers say. PMID- 22042993 TI - Preventing fractures in postmenopausal women: how to assess risk. PMID- 22042994 TI - "Poor tax" urged to address mental health issues. PMID- 22042995 TI - Early and continuing education: a prescription for achieving patient-centred care. PMID- 22042996 TI - Muddling thru models. PMID- 22042997 TI - Habit or addiction: the critical tension in deciding who should enforce hospital smoke-free policies. PMID- 22042999 TI - Tension gastrothorax causing cardiac arrest. PMID- 22043000 TI - Effectiveness of a quality-improvement program in improving management of primary care practices. AB - BACKGROUND: The European Practice Assessment program provides feedback and outreach visits to primary care practices to facilitate quality improvement in five domains (infrastructure, people, information, finance, and quality and safety). We examined the effectiveness of this program in improving management in primary care practices in Germany, with a focus on the domain of quality and safety. METHODS: In a before-after study, 102 primary care practices completed a practice assessment using the European Practice Assessment instrument at baseline and three years later (intervention group). A comparative group of 102 practices was included that completed their first assessment using this instrument at the time of the intervention group's second assessment. Mean scores were based on the proportion of indicators for which a positive response was achieved by all of the practices, on a scale of 0 to 100. RESULTS: We found significant improvements in all domains between the first and second assessments in the intervention group. In the domain of quality and safety, improvements in scores (mean scores were based on the proportion of indicators for which a positive response was achieved by all of the practices, on a scale of 0 to 100) were observed in the following dimensions: complaint management (from a mean score of 51.2 at first assessment to 80.7 at second assessment); analysis of critical incidents (from 79.1 to 89.6); and quality development, quality policy (from 40.7 to 55.6). Overall scores at the time of the second assessment were significantly higher in the intervention group than in the comparative group. INTERPRETATION: Primary care practices that completed the European Practice Assessment instrument twice over a three-year period showed improvements in practice management. Our findings show the value of the quality-improvement cycle in the context of practice assessment and the use of established organizational standards for practice management with the Europeaen Practice Assessment. PMID- 22043003 TI - Synergistic reversal of type 1 diabetes in NOD mice with anti-CD3 and interleukin 1 blockade: evidence of improved immune regulation. AB - Inflammatory cytokines are involved in autoimmune diabetes: among the most prominent is interleukin (IL)-1beta. We postulated that blockade of IL-1beta would modulate the effects of anti-CD3 monoclonal antibody (mAb) in treating diabetes in NOD mice. To test this, we treated hyperglycemic NOD mice with F(ab')(2) fragments of anti-CD3 mAb with or without IL-1 receptor antagonist (IL 1RA), or anti-IL-1beta mAb. We studied the reversal of diabetes and effects of treatment on the immune system. Mice that received a combination of anti-CD3 mAb with IL-1RA showed a more rapid rate of remission of diabetes than mice treated with anti-CD3 mAb or IL-1RA alone. Combination-treated mice had increased IL-5, IL-4, and interferon (IFN)-gamma levels in circulation. There were reduced pathogenic NOD-relevant V7 peptide-V7(+) T cells in the pancreatic lymph nodes. Their splenocytes secreted more IL-10, had increased arginase expression in macrophages and dendritic cells, and had delayed adoptive transfer of diabetes. After 1 month, there were increased concentrations of IgG1 isotype antibodies and reduced intrapancreatic expression of IFN-gamma, IL-6, and IL-17 despite normal splenocyte cytokine secretion. These studies indicate that the combination of anti-CD3 mAb with IL-1RA is synergistic in reversal of diabetes through a combination of mechanisms. The combination causes persistent remission from islet inflammation. PMID- 22043005 TI - Obesity, inflammation, and oral infections: are microRNAs the missing link? PMID- 22043004 TI - Gipr is essential for adrenocortical steroidogenesis; however, corticosterone deficiency does not mediate the favorable metabolic phenotype of Gipr(-/-) mice. AB - Glucose-dependent insulinotropic polypeptide (GIP) promotes glucose-dependent insulin secretion. However, GIP also enhances glucocorticoid secretion and promotes adiposity. Because obesity and diabetes are glucocorticoid dependent, we examined whether the effects of GIP on energy balance and glycemia are regulated by glucocorticoids using pharmacological activation of GIP receptor (GIPR) signaling with [d-Ala(2)]GIP in mice and in Y1 adrenocortical cells. Genetic elimination of GIPR activity was also studied in normal- and high-fat (HF)-fed Gipr-deficient (Gipr(-/-)) mice. [d-Ala(2)]GIP increased murine corticosterone levels in a GIPR-dependent manner. Conversely, basal corticosterone levels were reduced, whereas food deprivation resulted in significantly enhanced plasma corticosterone levels in Gipr(-/-) mice. [d-Ala(2)]GIP increased cAMP levels, activated extracellular signal?x{2013}related kinase (ERK)1/2, increased expression of steroidogenic genes, and increased neutral lipid storage in Y1GIPR cells. Gipr(-/-) adrenal glands demonstrated a twofold upregulation of the ACTH receptor mRNA and increased sensitivity to ACTH ex vivo. Although HF-fed Gipr(-/ ) mice exhibited significantly lower plasma corticosterone, glucocorticoid treated HF-fed Gipr(-/-) mice had similar energy balance and glycemia compared with Gipr(+)(/+) controls. Hence, although the Gipr is essential for adrenal steroidogenesis and links HF feeding to increased levels of corticosterone, reduced glucocorticoid levels do not significantly contribute to the enhanced metabolic phenotypes in HF-fed Gipr(-/-) mice. PMID- 22043006 TI - MicroRNA modulation in obesity and periodontitis. AB - The aim of this pilot investigation was to determine if microRNA expression differed in the presence or absence of obesity, comparing gingival biopsies obtained from patients with or without periodontal disease. Total RNA was extracted from gingival biopsy samples collected from 20 patients: 10 non-obese patients (BMI < 30 kg/m(2)) and 10 obese patients (BMI > 30 kg/m(2)), each group with 5 periodontally healthy sites and 5 chronic periodontitis sites. MicroRNA expression patterns were assessed with a quantitative microRNA PCR array to survey 88 candidate microRNA species. Four microRNA databases were used to identify potential relevant mRNA target genes of differentially expressed microRNAs. Two microRNA species (miR-18a, miR-30e) were up-regulated among obese individuals with a healthy periodontium. Two microRNA species (miR-30e, miR-106b) were up-regulated in non-obese individuals with periodontal disease. In the presence of periodontal disease and obesity, 9 of 11 listed microRNAs were significantly up-regulated (miR-15a, miR-18a, miR-22, miR-30d, miR-30e, miR-103, miR-106b, miR-130a, miR-142-3p, miR-185, and miR-210). Predicted targets include 69 different mRNAs from genes that comprise cytokines, chemokines, specific collagens, and regulators of glucose and lipid metabolism. The expression of specific microRNA species in obesity, which could also target and post transcriptionally modulate cytokine mRNA, provides new insight into possible mechanisms of how risk factors might modify periodontal inflammation and may represent novel therapeutic targets. PMID- 22043007 TI - The role for decorin in delayed-type hypersensitivity. AB - Decorin, a small leucine-rich proteoglycan, regulates extracellular matrix organization, growth factor-mediated signaling, and cell growth. Because decorin may directly modulate immune responses, we investigated its role in a mouse model of contact allergy (oxazolone-mediated delayed-type hypersensitivity [DTH]) in decorin-deficient (Dcn(-/-)) and wild-type mice. Dcn(-/-) mice showed a reduced ear swelling 24 h after oxazolone treatment with a concurrent attenuation of leukocyte infiltration. These findings were corroborated by reduced glucose metabolism, as determined by (18)fluordeoxyglucose uptake in positron emission tomography scans. Unexpectedly, polymorphonuclear leukocyte numbers in Dcn(-/-) blood vessels were significantly increased and accompanied by large numbers of flattened leukocytes adherent to the endothelium. Intravital microscopy and flow chamber and static adhesion assays confirmed increased adhesion and reduced transmigration of Dcn(-/-) leukocytes. Circulating blood neutrophil numbers were significantly increased in Dcn(-/-) mice 24 h after DTH elicitation, but they were only moderately increased in wild-type mice. Expression of the proinflammatory cytokine TNF-alpha was reduced, whereas syndecan-1 and ICAM-1 were overexpressed in inflamed ears of Dcn(-/-) mice, indicating that these adhesion molecules could be responsible for increased leukocyte adhesion. Decorin treatment of endothelial cells increased tyrosine phosphorylation and reduced syndecan-1 expression. Notably, absence of syndecan-1 in a genetic background lacking decorin rescued the attenuated DTH phenotype of Dcn(-/-) mice. Collectively, these results implicated a role for decorin in mediating DTH responses by influencing polymorphonuclear leukocyte attachment to the endothelium. This occurs via two nonmutually exclusive mechanisms that involve a direct antiadhesive effect on polymorphonuclear leukocytes and a negative regulation of ICAM-1 and syndecan-1 expression. PMID- 22043009 TI - Quantifying antigen-specific CD4 T cells during a viral infection: CD4 T cell responses are larger than we think. AB - The number of virus-specific CD8 T cells increases substantially during an acute infection. Up to 90% of CD8 T cells are virus specific following lymphocytic choriomeningitis virus (LCMV) infection. In contrast, studies identifying virus specific CD4 T cell epitopes have indicated that CD4 T cells often recognize a broader array of Ags than CD8 T cells, consequently making it difficult to accurately quantify the total magnitude of pathogen-specific CD4 T cell responses. In this study, we show that CD4 T cells become CD11a(hi)CD49d(+) after LCMV infection and retain this expression pattern into memory. During the effector phase, all the LCMV-specific IFN-gamma(+) CD4 T cells display a CD11a(hi)CD49d(+) cell surface expression phenotype. In addition, only memory CD11a(hi)CD49d(+) CD4 T cells make IFN-gamma after stimulation. Furthermore, upon secondary LCMV challenge, only CD11a(hi)CD49d(+) memory CD4 T cells from LCMV immune mice undergo proliferative expansion, demonstrating that CD11a(hi)CD49d(+) CD4 T cells are truly Ag specific. Using the combination of CD11a and CD49d, we demonstrate that up to 50% of the CD4 T cells are virus specific during the peak of the LCMV response. Our results indicate that the magnitude of the virus specific CD4 T cell response is much greater than previously recognized. PMID- 22043010 TI - Cross-talk between TCR and CCR7 signaling sets a temporal threshold for enhanced T lymphocyte migration. AB - Lymphocyte homing to, and motility within, lymph nodes is regulated by the chemokine receptor CCR7 and its two ligands CCL19 and CCL21. There, lymphocytes are exposed to a number of extracellular stimuli that influence cellular functions and determine the cell fate. In this study, we assessed the effect of TCR engagement on CCR7-mediated cell migration. We found that long-term TCR triggering of freshly isolated human T cells through CD3/CD28 attenuated CCR7 driven chemotaxis, whereas short-term activation significantly enhanced CCR7 mediated, but not CXCR4-mediated, migration efficiency. Short-term activation most prominently enhanced the migratory response of naive T cells of both CD4 and CD8 subsets. We identified distinct roles for Src family kinases in modulating CCR7-mediated T cell migration. We provide evidence that Fyn, together with Ca(2+)-independent protein kinase C isoforms, kept the migratory response of naive T cells toward CCL21 at a low level. In nonactivated T cells, CCR7 triggering induced a Fyn-dependent phosphorylation of the inhibitory Tyr505 of Lck. Inhibiting Fyn in these nonactivated T cells prevented the negative regulation of Lck and facilitated high CCR7-driven T cell chemotaxis. Moreover, we found that the enhanced migration of short-term activated T cells was accompanied by a synergistic, Src-dependent activation of the adaptor molecule linker for activation of T cells. Collectively, we characterize a cross-talk between the TCR and CCR7 and provide mechanistic evidence that the activation status of T cells controls lymphocyte motility and sets a threshold for their migratory response. PMID- 22043008 TI - PTEN negatively regulates engulfment of apoptotic cells by modulating activation of Rac GTPase. AB - Efficient clearance of apoptotic cells by phagocytes (efferocytosis) is critical for normal tissue homeostasis and regulation of the immune system. Apoptotic cells are recognized by a vast repertoire of receptors on macrophage that lead to transient formation of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] and subsequent cytoskeletal reorganization necessary for engulfment. Certain PI3K isoforms are required for engulfment of apoptotic cells, but relatively little is known about the role of lipid phosphatases in this process. In this study, we report that the activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a phosphatidylinositol 3-phosphatase, is elevated upon efferocytosis. Depletion of PTEN in macrophage results in elevated PtdIns(3,4,5)P(3) production and enhanced phagocytic ability both in vivo and in vitro, whereas overexpression of wild-type PTEN abrogates this process. Loss of PTEN in macrophage leads to activation of the pleckstrin homology domain containing guanine-nucleotide exchange factor Vav1 and subsequent activation of Rac1 GTPase, resulting in increased amounts of F-actin upon engulfment of apoptotic cells. PTEN disruption also leads to increased production of anti inflammatory cytokine IL-10 and decreased production of proinflammatory IL-6 and TNF-alpha upon engulfment of apoptotic cells. These data suggest that PTEN exerts control over efferocytosis potentially by regulating PtdIns(3,4,5)P(3) levels that modulate Rac GTPase and F-actin reorganization through Vav1 exchange factor and enhancing apoptotic cell-induced anti-inflammatory response. PMID- 22043011 TI - A comparative analysis of viral peptides presented by contemporary human and chimpanzee MHC class I molecules. AB - Genetic factors such as the MHC influence the immunocompetence of an individual. MHC genes are the most polymorphic genes in primates, which is often interpreted as an adaptation to establish good T cell responses to a wide range of (evolving) pathogens. Chimpanzee MHC (Patr) genes are less polymorphic than human MHC (HLA) genes, which is surprising because chimpanzee is the older species of the two and is therefore expected to display more variation. To quantify the effect of the reduced polymorphism, we compared the peptide binding repertoire of human and chimpanzee MHC molecules. Using a peptide-MHC binding predictor and proteomes of >900 mammalian viruses, we show that, at the population level, the total peptide binding repertoire of Patr-A molecules is ~36% lower than that of their human counterparts, whereas the reduction of the peptide binding repertoire of the Patr B locus is only 15%. In line with these results, different Patr-A molecules turn out to have largely overlapping peptide binding repertoires, whereas the Patr-B molecules are more distinct from each other. This difference is somewhat less apparent at the individual level, where we found that only 25% of the viruses are significantly better presented by "simulated" humans with heterozygous HLA-A and B loci. Taken together, our results indicate that the Patr-B molecules recovered more after the selective sweep, whereas the Patr-A locus shows the most signs of the selective sweep with regard to its peptide binding repertoire. PMID- 22043012 TI - Structure-based selection of small molecules to alter allele-specific MHC class II antigen presentation. AB - Class II major histocompatibility molecules are the primary susceptibility locus for many autoimmune disorders, including type 1 diabetes. Human DQ8 and I-A(g7), in the NOD mouse model of spontaneous autoimmune diabetes, confers diabetes risk by modulating presentation of specific islet peptides in the thymus and periphery. We used an in silico molecular docking program to screen a large "druglike" chemical library to define small molecules capable of occupying specific structural pockets along the I-A(g7) binding groove, with the objective of influencing presentation to T cells of the autoantigen insulin B chain peptide consisting of amino acids 9-23. In this study we show, using both murine and human cells, that small molecules can enhance or inhibit specific TCR signaling in the presence of cognate target peptides, based upon the structural pocket targeted. The influence of compounds on the TCR response was pocket dependent, with pocket 1 and 6 compounds inhibiting responses and molecules directed at pocket 9 enhancing responses to peptide. At nanomolar concentrations, the inhibitory molecules block the insulin B chain peptide consisting of amino acids 9-23, endogenous insulin, and islet-stimulated T cell responses. Glyphosine, a pocket 9 compound, enhances insulin peptide presentation to T cells at concentrations as low as 10 nM, upregulates IL-10 secretion, and prevents diabetes in NOD mice. These studies present a novel method for identifying small molecules capable of both stimulating and inhibiting T cell responses, with potentially therapeutic applications. PMID- 22043013 TI - Paxillin associates with the microtubule cytoskeleton and the immunological synapse of CTL through its leucine-aspartic acid domains and contributes to microtubule organizing center reorientation. AB - The cytoskeletal adaptor protein paxillin localizes to the microtubule organizing center (MTOC) in T cells and, upon target cell binding, is recruited to the supramolecular activation complex (SMAC). We mapped the region of paxillin that associates with both the MTOC and SMAC to the leucine-aspartic acid (LD) domains and showed that a protein segment containing LD2-4 was sufficient for MTOC and SMAC recruitment. Examination of the localization of paxillin at the SMAC revealed that paxillin localizes to the peripheral area of the SMAC along with LFA-1, suggesting that LFA-1 may contribute to its recruitment. LFA-1 or CD3 engagement alone was insufficient for paxillin recruitment because there was no paxillin accumulation at the site of CTL contact with anti-LFA-1- or anti-CD3 coated beads. In contrast, paxillin accumulation was detected when beads coated with both anti-CD3 and anti-LFA-1 were bound to CTL, suggesting that signals from both the TCR and LFA-1 are required for paxillin accumulation. Paxillin was shown to be phosphorylated downstream of ERK, but when we generated a mutation (S83A/S130A) that abolished the mobility shift as a result of phosphorylation, we found that paxillin still bound to the MTOC and was recruited to the SMAC. Furthermore, ERK was not absolutely required for MTOC reorientation in CTL that require ERK for killing. Finally, expression of the LD2-4 region of paxillin substantially reduced MTOC reorientation. These studies demonstrated that paxillin is recruited, through its LD domains, to sites of integrin engagement and may contribute to MTOC reorientation required for directional degranulation. PMID- 22043014 TI - Selective upregulation of microRNA expression in peripheral blood leukocytes in IL-10-/- mice precedes expression in the colon. AB - IL-10(-/-) mice, an animal model of Th1-mediated inflammatory bowel disease, were screened for the expression of 600 microRNAs (miRNAs) using colonic tissues and PBLs from animals having either mild inflammation or severe intestinal inflammation. The development of colonic inflammation in IL-10(-/-) mice was accompanied by upregulation in the expression of 10 miRNAs (miR-19a, miR-21, miR 31, miR-101, miR-223, miR-326, miR-142-3p, miR-142-5p, miR-146a, and miR-155). Notably, the expression of all of these miRNAs plus miR-375 was elevated in PBLs of IL-10(-/-) mice at a time when colonic inflammation was minimal, suggesting that changes in specific miRNAs in circulating leukocytes may be harbingers of ensuing colonic pathology. In vitro exposure of colonic intraepithelial lymphocytes to IL-10 resulted in downregulation of miR-19a, miR-21, miR-31, miR 101, miR-223, and miR-155. Interestingly, unlike IL-10(-/-) mice, changes in miRNAs in PBL of dextran sulfate sodium-treated mice were minimal but selectively elevated in the colon after pathology was severe. We further show that miR-223 is a negative regulator of the Roquin ubiquitin ligase, Roquin curtails IL-17A synthesis, and the 3' untranslated region of Roquin is a target for miR-223, thus defining a molecular pathway by which IL-10 modulates IL-17-mediated inflammation. To identify additional miRNAs that may be involved in the regulation of Roquin, transcriptome analysis was done using cDNAs from HeLa cells transfected with 90 miRNA mimics. Twenty-six miRNAs were identified as potential negative regulators of Roquin, thus demonstrating functional complexity in gene expression regulation by miRNAs. PMID- 22043015 TI - Attenuated atherosclerotic lesions in apoE-Fcgamma-chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of regulatory T cells. AB - Though the presence of antioxidized low-density lipoprotein IgG is well documented in clinical and animal studies, the role for FcgammaRs to the progression of atherosclerosis has not been studied in detail. In the current study, we investigated the role for activating FcgammaR in the progression of atherosclerosis using apolipoprotein E (apoE)-Fcgamma-chain double-knockout (DKO) mice. Relative to apoE knockout (KO) mice, arterial lesion formation was significantly decreased in apoE-Fcgamma-chain DKO mice. Bone marrow chimera studies showed reduced lesions in apoE KO mice receiving the bone marrow of apoE Fcgamma-chain DKO mice. Compared to apoE KO mice, antioxidized low-density lipoprotein IgG1 (Th2) and IgG2a (Th1), IL-10, and IFN-gamma secretion by activated T cells was increased in apoE-Fcgamma-chain DKO mice. These findings suggest that reduced atherosclerotic lesion in apoE-Fcgamma-chain DKO mice is not due to a Th1/Th2 imbalance. Interestingly, the number of Th17 cells and the secretion of IL-17 by activated CD4(+) cells were decreased in apoE-Fcgamma-chain DKO mice. Notably, the number of regulatory T cells, expression of mRNA, and secretion of TGF-beta and IL-10 were increased in apoE-Fcgamma-chain DKO mice. Furthermore, secretions of IL-6 and STAT-3 phosphorylation essential for Th17 cell genesis were reduced in apoE-Fcgamma-chain DKO mice. Importantly, decrease in Th17 cells in apoE-Fcgamma-chain DKO mice was due to reduced IL-6 release by APC of apoE-Fcgamma-chain DKO mice. Collectively, our data suggest that activating FcgammaR promotes atherosclerosis by inducing a Th17 response in the hyperlipidemic apoE KO mouse model. PMID- 22043017 TI - Lung CD103+ dendritic cells efficiently transport influenza virus to the lymph node and load viral antigen onto MHC class I for presentation to CD8 T cells. AB - The uptake, transport, and presentation of Ags by lung dendritic cells (DCs) are central to the initiation of CD8 T cell responses against respiratory viruses. Although several studies have demonstrated a critical role of CD11b(low/neg)CD103(+) DCs for the initiation of cytotoxic T cell responses against the influenza virus, the underlying mechanisms for its potent ability to prime CD8 T cells remain poorly understood. Using a novel approach of fluorescent lipophilic dye-labeled influenza virus, we demonstrate that CD11b(low/neg)CD103(+) DCs are the dominant lung DC population transporting influenza virus to the posterior mediastinal lymph node as early as 20 h postinfection. By contrast, CD11b(high)CD103(neg) DCs, although more efficient for taking up the virus within the lung, migrate poorly to the lymph node and remain in the lung to produce proinflammatory cytokines instead. CD11b(low/neg)CD103(+) DCs efficiently load viral peptide onto MHC class I complexes and therefore uniquely possess the capacity to potently induce proliferation of naive CD8 T cells. In addition, the peptide transporters TAP1 and TAP2 are constitutively expressed at higher levels in CD11b(low/neg)CD103(+) DCs, providing, to our knowledge, the first evidence of a distinct regulation of the Ag-processing pathway in these cells. Collectively, these results show that CD11b(low/neg)CD103(+) DCs are functionally specialized for the transport of Ag from the lung to the lymph node and also for efficient processing and presentation of viral Ags to CD8 T cells. PMID- 22043016 TI - Negative selection by IgM superantigen defines a B cell central tolerance compartment and reveals mutations allowing escape. AB - To analyze B lymphocyte central tolerance in a polyclonal immune system, mice were engineered to express a superantigen reactive to IgM of allotype b (IgM(b)). IgM(b/b) mice carrying superantigen were severely B cell lymphopenic, but small numbers of B cells matured. Their sera contained low levels of IgG and occasionally high levels of IgA. In bone marrow, immature B cells were normal in number, but internalized IgM and had a unique gene expression profile, compared with those expressing high levels of surface IgM, including elevated recombinase activator gene expression. A comparable B cell population was defined in wild type bone marrows, with an abundance suggesting that at steady state ~20% of normal developing B cells are constantly encountering autoantigens in situ. In superantigen-expressing mice, as well as in mice carrying the 3H9 anti-DNA IgH transgene, or 3H9 H along with mutation in the murine kappa-deleting element RS, IgM internalization was correlated with CD19 downmodulation. CD19(low) bone marrow cells from 3H9;RS(-/-) mice were enriched in L chains that promote DNA binding. Our results suggest that central tolerance and attendant L chain receptor editing affect a large fraction of normal developing B cells. IgH(a/b) mice carrying the superantigen had a ~50% loss in follicular B cell numbers, suggesting that escape from central tolerance by receptor editing from one IgH allele to another was not a major mechanism. IgM(b) superantigen hosts reconstituted with experimental bone marrow were demonstrated to be useful in revealing pathways involved in central tolerance. PMID- 22043018 TI - Molecular characterization of a Streptococcus gallolyticus genomic island encoding a pilus involved in endocarditis. AB - BACKGROUND: Streptococcus gallolyticus is a causative agent of infective endocarditis associated with colon cancer. Genome sequence of strain UCN34 revealed the existence of 3 pilus loci (pil1, pil2, and pil3). Pili are long filamentous structures playing a key role as adhesive organelles in many pathogens. The pil1 locus encodes 2 LPXTG proteins (Gallo2178 and Gallo2179) and 1 sortase C (Gallo2177). Gallo2179 displaying a functional collagen-binding domain was referred to as the adhesin, whereas Gallo2178 was designated as the major pilin. METHODS: S. gallolyticus UCN34, Pil1(+) and Pil1(-), expressing various levels of pil1, and recombinant Lactococcus lactis strains, constitutively expressing pil1, were studied. Polyclonal antibodies raised against the putative pilin subunits Gallo2178 and Gallo2179 were used in immunoblotting and immunogold electron microscopy. The role of pil1 was tested in a rat model of endocarditis. RESULTS: We showed that the pil1 locus (gallo2179-78 77) forms an operon differentially expressed among S. gallolyticus strains. Short pilus appendages were identified both on the surface of S. gallolyticus UCN34 and recombinant L. lactis-expressing pil1. We demonstrated that Pil1 pilus is involved in binding to collagen, biofilm formation, and virulence in experimental endocarditis. CONCLUSIONS: This study identifies Pil1 as the first virulence factor characterized in S. gallolyticus. PMID- 22043019 TI - Disseminated varicella infection caused by varicella vaccine strain in a child with low invariant natural killer T cells and diminished CD1d expression. AB - BACKGROUND: Live attenuated varicella vaccine is considered a safe vaccine with serious adverse effects reported only in immunocompromised children. We describe a severe life-threatening infection with varicella vaccine virus causing rash and pneumonitis in a 6-year-old boy with no apparent immunodeficiency. METHODS AND RESULTS: Polymerase chain reaction (PCR) analysis of vesicle swab samples demonstrated varicella zoster virus (VZV). Sequencing of the PCR product demonstrated 100% homology with human herpesvirus 3 strain VZV-Oka ORF62 gene. Routine immunologic investigations failed to demonstrate any abnormality. Total leukocyte, lymphocyte, and neutrophil counts and lymphocyte subsets were normal. Immunoglobulins, C3, C4, and CH50 were intact. Specific IgG to protein and polysaccharide antigens and to Epstein-Barr virus and cytomegalovirus were present. Normal lymphocyte proliferation to phytohemagglutinin and VZV antigens was detected. Neutrophil function and natural killer (NK) cell activity were normal. The analysis of invariant NK T (iNKT) cell numbers and function revealed diminished iNKT cells, reported once previously and unique to our patient, deficient expression of the cognate receptor, CD1d. CONCLUSIONS: This report provides a further link between deficiency of the iNKT/CD1d pathway and increased susceptibility to varicella vaccine virus, suggesting an important role of this innate pathway in host defense against yet another member of the herpesvirus family. PMID- 22043020 TI - Unmasking potential intracellular roles for dysferlin through improved immunolabeling methods. AB - Mutations in the DYSF gene that severely reduce the levels of the protein dysferlin are implicated in muscle-wasting syndromes known as dysferlinopathies. Although studies of its function in skeletal muscle have focused on its potential role in repairing the plasma membrane, dysferlin has also been found, albeit inconsistently, in the sarcoplasm of muscle fibers. The aim of this article is to study the localization of dysferlin in skeletal muscle through optimized immunolabeling methods. We studied the localization of dysferlin in control rat skeletal muscle using several different methods of tissue collection and subsequent immunolabeling. We then applied our optimized immunolabeling methods on human cadaveric muscle, control and dystrophic human muscle biopsies, and control and dysferlin-deficient mouse muscle. Our data suggest that dysferlin is present in a reticulum of the sarcoplasm, similar but not identical to those containing the dihydropyridine receptors and distinct from the distribution of the sarcolemmal protein dystrophin. Our data illustrate the importance of tissue fixation and antigen unmasking for proper immunolocalization of dysferlin. They suggest that dysferlin has an important function in the internal membrane systems of skeletal muscle, involved in calcium homeostasis and excitation-contraction coupling. PMID- 22043021 TI - Deficiency of pro-apoptotic Hrk attenuates programmed cell death in the developing murine nervous system but does not affect Bcl-x deficiency-induced neuron apoptosis. AB - The BCL-2 family includes both pro- and anti-apoptotic proteins, which regulate programmed cell death during development and in response to various apoptotic stimuli. The BH3-only subgroup of pro-apoptotic BCL-2 family members is critical for the induction of apoptotic signaling, by binding to and neutralizing anti apoptotic BCL-2 family members. During embryonic development, the anti-apoptotic protein BCL-X(L) plays a critical role in the survival of neuronal populations by regulating the multi-BH domain protein BAX. In this study, the authors investigated the role of Harakiri (HRK), a relatively recently characterized BH3 only molecule in disrupting the BAX-BCL-X(L) interaction during nervous system development. Results indicate that HRK deficiency significantly reduces programmed cell death in the nervous system. However, HRK deficiency does not significantly attenuate the widespread apoptosis seen in the Bcl-x (-/-) embryonic nervous system, indicating that other BH3-only molecules, alone or in combination, may regulate BAX activation in immature neurons. PMID- 22043022 TI - Subcellular distribution and relative expression of fibrocyte markers in the CD/1 mouse cochlea assessed by semiquantitative immunogold electron microscopy. AB - Spiral ligament fibrocytes function in cochlear homeostasis, maintaining the endocochlear potential by participating in potassium recycling, and fibrocyte degeneration contributes to hearing loss. Their superficial location makes them amenable to replacement by cellular transplantation. Fibrocyte cultures offer one source of transplantable cells, but determining what fibrocyte types they contain and what phenotype transplanted cells may adopt is problematic. Here, we use immunogold electron microscopy to assess the relative expression of markers in native fibrocytes of the CD/1 mouse spiral ligament. Caldesmon and aquaporin 1 are expressed more in type III fibrocytes than any other type. S-100 is strongly expressed in types I, II, and V fibrocytes, and alpha1Na,K-ATPase is expressed strongly only in types II and V. By combining caldesmon or aquaporin 1 with S-100 and alpha1Na,K-ATPase, a ratiometric analysis of immunogold density distinguishes all except type II and type V fibrocytes. Other putative markers (creatine kinase BB and connective tissue growth factor) did not provide additional useful analytical attributes. By labeling serial sections or by double or triple labeling with combinations of three antibodies, this technique could be used to distinguish all except type II and type V fibrocytes in culture or after cellular transplantation into the lateral wall. PMID- 22043023 TI - Expression of dentin sialophosphoprotein in non-mineralized tissues. AB - Dentin sialophosphoprotein (DSPP) and its cleaved products, dentin phosphoprotein (DPP) and dentin sialoprotein (DSP), play important roles in biomineralization. Believed to be tooth specific, the authors' group revealed its expression in bone, and more recently, they and other groups also showed its expression in a few types of soft tissues. In this study, the authors systematically examined the expression of DSPP in a variety of non-mineralized tissues using reverse transcription polymerase chain reaction (RT-PCR), real-time PCR, Western immunoblotting, and immunohistochemistry analyses in wild-type mice as well as beta-galactosidase assays in the Dspp lacZ knock-in mice. These approaches showed the presence of DSPP in the salivary glands, cartilage, liver, kidney, and brain and its absence in the heart and spleen. Real-time PCR showed that the expression levels of DSPP mRNA in salivary glands, cartilage, liver, and kidney were higher than in the bone. Interestingly, DSPP was observed in the pericytes of blood vessels in the dental pulp, which are believed to be able to differentiate into odontoblasts. On the basis of these observations, the authors conclude that DSPP and/or its cleaved products may fulfill important functions in certain non mineralized tissues in addition to its role in biomineralization. PMID- 22043024 TI - Claudins and ki-67: potential markers to differentiate low- and high-grade transitional cell carcinomas of the urinary bladder. AB - Updated classification of urothelial cell cancer differentiates low-grade and high-grade cancers, which determines potential clinical outcome. Substantial interobserver variability necessitates new biomarkers to ensure classification. Claudins' specific expression pattern characterizes normal tissues, different tumor types, and defined grades of tumor differentiation. The aim of this study was to examine the expression pattern of claudins and proliferation marker Ki-67 in low-grade and high-grade urothelial cell cancers compared with independent control samples of non-tumorous urothelium, as well as to reveal the predictive usefulness of claudins. The expression of claudins-1, -2, -3, -4, -5, -7, and -10 and Ki-67 was studied with quantitative immunohistochemistry and real-time RT-PCR with relative quantification in 103 samples: 86 urothelial cell cancers (27 low grade, 59 high grade) and 17 non-tumorous urothelia. Results were analyzed regarding overall survival and recurrence-free period as well. High-grade tumors overall showed significantly higher claudin-4 and Ki-67 and significantly lower claudin-7 expression when compared with low-grade ones. High-grade tumors revealed significantly shorter overall survival in Kaplan-Meier analysis. Claudin 4, claudin-7, and Ki-67 might be used as potential markers to differentiate low grade and high-grade urothelial cell cancers, thereby possibly enhancing accuracy of pathological diagnosis and adding further information to clinical outcome. PMID- 22043025 TI - Internalizing problems of adults with learning disabilities: a meta-analysis. AB - In this article the authors report a meta-analysis that examines the association between internalizing problems (anxiety and depressive symptoms) and learning disabilities (LD) in adults. Two hypotheses about the relationship between internalizing problems and LD in adults are posited and tested: the abeyance hypothesis (internalizing problems decline in adulthood) and the continuance hypothesis (internalizing problems continue in adulthood). From an initial pool of 171 relevant studies, 15 studies met the inclusion criteria, with eight published articles and seven dissertations yielding 48 effect sizes, N Total = 16,239). The overall effect size was significant and of medium magnitude (d = 0.51, p < .001). Results from the study suggest support for the continuance hypothesis, with rates of adult internalizing problems similar to those found in studies of children and adolescents with LD. Moderating variables are explored, and implications for practice and research are offered. PMID- 22043026 TI - An exploratory study of a number sense program to develop kindergarten students' number proficiency. AB - This study examined the effectiveness of a number sense program on kindergarten students' number proficiency and responsiveness to treatment as a function of students' risk for mathematics difficulties. The program targeted development of relationships among numbers (e.g., spatial, more and less). A total of 101 kindergarten students (not at risk: 22 control and 36 experimental; at risk: 18 and 25) from five classrooms in a high-poverty elementary school participated in the study. Using a quasi-experimental design, classrooms were randomly assigned to either the intervention (number sense instruction, NSI) or control condition. Results indicated significant differences favoring the treatment students on all measures of number sense (e.g., spatial relationships, more and less relationships, benchmarks of five and ten, nonverbal calculations) at posttest and on a 3-week retention test. Furthermore, the effects were not mediated by at risk status, suggesting that NSI may benefit a wide range of students. Implications in terms of preventing early mathematical learning difficulties are discussed. PMID- 22043027 TI - Early writing deficits in preschoolers with oral language difficulties. AB - The purpose of this study was to investigate whether preschool children with language impairments (LI), a group with documented reading difficulties, also experience writing difficulties. In addition, a purpose was to examine if the writing outcomes differed when children had concomitant cognitive deficits in addition to oral language problems. A group of 293 preschool children were administered an assessment battery that included measures to examine oral language, nonverbal cognition, emergent reading, and writing. Children were divided into four groups based on their language and cognitive performance. The findings from this study show that as early as preschool, children with weaker oral language skills lag behind their peers with stronger oral language skills in terms of their writing-related skills. Children with oral language and cognitive deficits performed more poorly than children whose deficits were confined to oral language. A child's cognitive ability also has an impact on emergent writing skills, but it appears to be moderated by oral language skills. These results are consistent with research documenting links between preschool language and emergent reading in children with a history of LI. PMID- 22043032 TI - Sex work and sexually transmitted infections in Asia: a biosocial analysis. AB - The Harvard University Asia Center hosted a symposium in October 2010 focused on sex work and sexually transmitted infections in Asia, engaging a biosocial approach to promote sexual health in this region. Asia has an estimated 151 million cases of curable sexually transmitted infections (STIs; eg, syphilis, gonorrhea, chlamydia) each year, with commercial sex interactions playing a large role in ongoing transmission. Substantial human movement and migration, gender inequalities, and incipient medical and legal systems in many states stymie effective STI control in Asia. The articles in this supplement provide theoretical and empirical pathways to improving the sexual health of those who sell and purchase commercial sex in Asia. The unintended health consequences of various forms of regulating commercial sex are also reviewed, emphasizing the need to carefully consider the medical and public health consequences of new and existing policies and laws. PMID- 22043033 TI - Reframing the interpretation of sex worker health: a behavioral-structural approach. AB - Expanding sexually transmitted infection (STI) epidemics in many parts of Asia increase the importance of effective human immunodeficiency virus (HIV)/STI prevention programs for female sex workers. Designing sex worker health research and programs demands a well-stated conceptual approach, especially when one is interpreting the relationship between local policy environments and sex worker health. However, the core principles of the 2 most common conceptual approaches used in sex worker health programs--abolitionism and empowerment--have frequently divergent assumptions and implications. The abolitionist approach sees major aspects of the sex industry as fundamentally coercive and exploitative of women and supports dismantling all or parts of the sex sector. The empowerment approach strengthens sex workers' agency and rights in order to build collective self efficacy and have women invested in implementing their own HIV/STI prevention programs. This review compares these approaches using implication analysis and empirical cases from Asia. The misperception of an unresolvable gap between the 2 approaches ignores common ground that forms the basis of a new behavioral structural conceptual framework. Explicitly accounting for the interaction between female sex worker behaviors and larger structures and policies, a behavioral-structural approach may provide a solid foundation for sex work research and programs. PMID- 22043034 TI - Clients of female sex workers: a population-based survey of China. AB - The control of HIV and other sexually transmitted infections (STI) is a challenge in China, with female sex workers (FSW) and male clients suspected as bridge groups. This study used a 2006 national probability survey of 2,707 adult men. Among men 15-49 years old, the prevalence of FSW contacts last year was 4.2% (95% CI, 3.3-5.2) overall, with 7.2% (CI, 5.9-8.7) in urban and 1.8% (CI, 1.0-3.3) in rural areas. In urban areas, the men most at risk for FSW were high income, often traveled, engaged in business entertaining, ages 25-39, and had early sex histories. When compared to men with only wife or stable sex partner, those most likely to report STI last year also reported FSW sex of any type (aOR,13.10; CI, 5.87-29.42). Additionally, when compared to men reporting consistent condom use with FSW, men with inconsistent condom use had elevated STI (aOR, 3.71; CI, 1.18 11.66). Additional efforts are needed for high income men in urban areas, and on consistent condom use with FSW. PMID- 22043035 TI - HIV, sex work, and civil society in China. AB - Harm reduction programs for sex workers have been hampered by the prioritization of law enforcement over AIDS prevention. For example, the April 2010 "strike hard" campaign against prostitution in Beijing, during which bars, nightclubs, saunas, and karaoke bars were raided, created an atmosphere that critically impeded human immunodeficiency virus (HIV) outreach activities for sex workers. In China, criminalization has limited the growth of a coherent and cohesive set of nongovernmental organization (NGO) actors working with sex workers to prevent HIV infection. Compared with other risk groups for HIV sexual transmission, such as men who have sex with men, the NGO community for sex workers is fragmented and poorly coordinated with government efforts, and basic rights for sex workers are often violated. This article examines civil society groups working on AIDS prevention and care for female sex workers in China and reviews constraints to their operations. China's HIV prevention programs for sex workers are compared with sex worker HIV prevention in other Asian states where more well-developed NGOs exist and criminalization has been better balanced with harm reduction approaches, and recommendations are offered on improving China's policies and programs. PMID- 22043036 TI - Police-related experiences and HIV risk among female sex workers in Andhra Pradesh, India. AB - Research suggests experiences with police are related to human immunodeficiency virus (HIV) sexual risk among women working as sex workers. However, little is known about the links between specific police-related behaviors and HIV vulnerability. We examine whether 5 police-related experiences are associated with measures of HIV risk and violence among a sample of female sex workers (FSWs) in Andhra Pradesh, India, and consider the implications for HIV prevention. FSWs at least 18 years of age (n = 835) were recruited through respondent-driven sampling for a cross-sectional survey conducted as part of Avahan, the India AIDS Initiative. Using logistic regression models adjusted for age, age at start of sex work, and sex work venue, we assessed police-related experiences reported by FSWs in relation to HIV risk behaviors and violence. Results showed having sex with police to avoid trouble, giving gifts to police to avoid trouble, having police take condoms away, experiencing a workplace raid, and being arrested were associated with sexually transmitted infection symptoms, inconsistent condom use, acceptance of more money for sex without a condom, and experience of client violence. These findings suggest a need for interventions targeting police-FSW interactions to reduce HIV vulnerability among FSWs. PMID- 22043037 TI - Sex trafficking and initiation-related violence, alcohol use, and HIV risk among HIV-infected female sex workers in Mumbai, India. AB - Female sex workers (FSWs) are the group at greatest risk for human immunodeficiency virus (HIV) infection in India. Women and girls trafficked (ie, forced or coerced) into sex work are thought to be at even greater risk because of high exposure to violence and unprotected sex, particularly during the early months of sex work, that is, at initiation. Surveys were completed with HIV infected FSWs (n = 211) recruited from an HIV-related service organization in Mumbai, India. Approximately 2 in 5 participants (41.7%) reported being forced or coerced into sex work. During the first month in sex work, such FSWs had higher odds of sexual violence (adjusted odds ratio [AOR], 3.1; 95% confidence interval [CI], 1.6-6.1), >= 7 clients per day (AOR, 3.3; 1.8-6.1), no use of condoms (AOR, 3.8, 2.1-7.1), and frequent alcohol use (AOR, 1.9; 1.0-3.4) than HIV-infected FSWs not entering involuntarily. Those trafficked into sex work were also at higher odds for alcohol use at first sex work episode (AOR, 2.2; 95% CI, 1.2 4.0). These results suggest that having been trafficked into sex work is prevalent among this population and that such FSWs may face high levels of sexual violence, alcohol use, and exposure to HIV infection in the first month of sex work. Findings call into question harm reduction approaches to HIV prevention that rely primarily on FSW autonomy. PMID- 22043038 TI - Violence in contract work among female sex workers in Andhra Pradesh, India. AB - BACKGROUND: Female sex workers (FSWs) are vulnerable to physical and sexual violence at work. This article examines the prevalence of recent physical and sexual violence victimization and associations of type of sex work among a large sample of young FSWs. METHOD: We used data from a cross-sectional survey on sex trafficking and sex work in southern India that included 1138 FSWs aged 18-25 years residing in 3 districts of Andhra Pradesh state. The independent variable was organization of sex work. FSWs on contract at sex work establishments outside their home district were classified as contract workers, as compared with women who worked autonomously within their home district. Using logistic regression models adjusted for sociodemographic factors, we assessed the relation between contract/ non-contract sex work and various forms of violence experienced by FSWs. RESULTS: Results indicate a high prevalence of work-related physical and sexual violence; 50% FSWs reported physical violence, and 77% reported sexual violence. FSWs performing contract work were at increased risk of physical and sexual violence at work, compared with women engaged in sex work in their home districts. CONCLUSIONS: The findings that contract work outside the home district increases the vulnerabilities faced by FSWs in India suggest that violence and disease prevention services aimed at FSWs would be more effective if organization of sex work--as contract or noncontract--is taken into account. PMID- 22043039 TI - Differentiation therapy: targeting human renal cancer stem cells with interleukin 15. AB - BACKGROUND: Many renal cancer patients experience disease recurrence after immunotherapy or combined treatments due to persistence of cancer stem cells (CSCs). The identification of reliable inducers of CSC differentiation may facilitate the development of efficient strategies for eliminating CSCs. We investigated whether interleukin 15 (IL-15), a regulator of kidney homeostasis, induces the differentiation of CD105-positive (CD105(+)) CSCs from human renal cancers. METHODS: CD105(+) CSCs were cultured to preserve their stem cell properties and treated with recombinant human IL-15 (rhIL-15) to evaluate their ability to differentiate, to acquire sensitivity to chemotherapeutic drugs, and to form spheroids in vitro and tumors in vivo. Expression of stem cell and epithelial markers were studied by flow cytometry, immunocytochemistry, and immunoblotting. Identification of a CSC side population fraction and its sensitivity to chemotherapy drugs and expression of ATP-binding cassette (ABC) transporters and aldehyde dehydrogenase (ALDH) activities were determined by flow cytometry. Spheroid formation was determined in limiting dilution assay. Xenograft tumors were generated in severe combined immunodeficient mice (n = 12 18 mice per group). All statistical tests were two-sided. RESULTS: CD105(+) CSCs treated with rhIL-15 at 10 pg/mL differentiated into cells expressing epithelial markers. rhIL-15 induced epithelial differentiation of all CD105(+) CSCs subsets and blocked CSC self-renewal (sphere-forming ability) and their tumorigenic properties in severe combined immunodeficient mice. Vinblastine and paclitaxel induced statistically significant higher levels of apoptosis in rhIL-15 differentiated epithelial cells compared with CD105(+) CSCs (mean percentage of apoptotic cells, vinblastine: 33% vs 16.5%, difference = 16.5%, 95% confidence interval = 12.25% to 20.74%, P = .0025; paclitaxel: 35% vs 11.6%, difference = 23.4%, 95% confidence interval = 22.5% to 24.24%, P = .0015). The higher sensitivity of rhIL-15-differentiated epithelial cells to chemotherapeutic drugs was associated with loss of detoxifying mechanisms such as ALDH and ABC transporter activities. CONCLUSION: IL-15 directs the epithelial differentiation of renal CSCs and meets the criteria for a treatment strategy: CSC pool depletion and generation of differentiated nontumorigenic cells that are sensitive to chemotherapeutic agents. PMID- 22043040 TI - The treatment of individual patients is more than a trial. PMID- 22043041 TI - Strategies to translate preclinical information to breast cancer patient benefit. AB - Despite the progress in understanding breast cancer biology, translation of basic findings into clinical applications still appears to be a complex process, and few molecular markers/signatures are in routine clinical use or currently challenged for their clinical utility. Disease complexity, certainly, represents an obstacle to successful translation, but methodological pitfalls in development and validation steps also contribute. Translational research should be planned as a round-trip from the bench to the bedside and back. The preoperative/neoadjuvant setting represents an ideal model because it allows identification and validation of treatment response predictors and of pharmacodynamic markers associated with clinical downstaging, investigations on in vivo action mechanism of drugs, and indirect validation of findings from preclinical models. Availability of well annotated, high-quality biospecimens; standardized, reproducible, and robust assays to detect molecular markers/signatures even on few cells; prospective planning of study design; and regulatory issues adequately fitting preclinical and clinical needs represent fundamental assets for translational studies. PMID- 22043042 TI - The value of genomic analysis of breast cancer in drug development. AB - Improving the success rate and reducing the time that it takes to bring a new drug to the market represent important challenges for both academia and the pharmaceutical industry. High-throughput genomic analysis of cancer may assist streamlining this process through providing clinically relevant response markers, suggesting rational combination treatment strategies for biologically targeted agents and defining the next generation of therapeutic targets. PMID- 22043043 TI - Biomarkers predicting clinical benefit: fact or fiction? AB - Preoperative therapy is increasingly used in operable disease to improve the chance for breast-conservative surgery. Moreover, this strategy allows for a better definition of patient prognosis. Independently from stage at diagnosis and breast cancer subtype, the achievement of a pathological complete response (pCR) is a surrogate marker for long-term outcome. The likelihood of pCR depends on tumor biology, being poorly differentiated tumors with ductal histology, absence of hormone receptors, and high proliferation rate those with a higher chance of achieving a CR. However, pCR is a late efficacy parameter that can be evaluated at the end of the preoperative treatment; moreover, a pCR is achieved in a minority of patients and is not an appropriate efficacy measure for neoadjuvant endocrine therapy. The predictive role of tumor biomarkers such as p53, microtubule-associated tau protein, and poly (ADP-ribose) polymerase will be reviewed along with potential markers of early treatment effect. PMID- 22043044 TI - Molecular oncology and the neoadjuvant setting: the perfect blend for treatment personalization and clinical trial design. AB - Breast cancer is a heterogeneous disease. Predictive molecular markers are crucial in patient management, but the only recommended predictive biomarkers are estrogen and progesterone receptors and HER2. There are many new targeted therapies, and although the target pathway expression is readily analyzed on conventional pathology, the dynamic response cannot be assessed and pathway expression is no guarantee it has a major driver role, even if mutated. Selecting therapies requires considering the patient, the molecular characteristics of the tumor, and the microenvironment of the tumor. Thus, the integration of molecular pathology, imaging, and early tumor biological response to therapy may provide evidence of drug activity and allow more rapid changes of therapy. The adaptive response of the tumor is a key resistance mechanism that can be assessed readily in the neoadjuvant setting. Although there are no markers that meet all surrogacy criteria, their use could provide crucial information on mechanisms of drug sensitivity/resistance. Validation of such markers requires a major emphasis on neoadjuvant trials to relate early-biomarker response to outcome. PMID- 22043045 TI - Assessing early therapeutic response to bevacizumab in primary breast cancer using magnetic resonance imaging and gene expression profiles. AB - Antiangiogenic therapy is a promising approach for the treatment of breast cancer. In practice, however, only a subset of patients who receive antiangiogenic drugs demonstrate a significant response. A key challenge, therefore, is to discover biomarkers that are predictive of response to antiangiogenic therapy. To address this issue, we have designed a window-of opportunity study in which bevacizumab is administered as a short-term first-line treatment to primary breast cancer patients. Central to our approach is the use of a detailed pharmacodynamic assessment, consisting of pre- and post-bevacizumab multi-parametric magnetic resonance imaging scans and core biopsies for exon array gene expression analysis. Here, we illustrate three intrinsic patterns of response to bevacizumab and discuss the molecular mechanisms that may underpin each. Our results illustrate how the combination of dynamic imaging data and gene expression profiles can guide the development of biomarkers for predicting response to antiangiogenic therapy. PMID- 22043047 TI - kConFab: a familial breast cancer consortium facilitating research and translational oncology. AB - In 2005, 100,514 Australians were diagnosed with cancer, and over 10,000 of these cancers will be due to heritable causes. The impact of familial cancer by definition extends beyond the individual, affecting tens of thousands of parents, siblings, and children. The study of familial cancer causes has arguably made the greatest single contribution to our understanding of cancer biology. This knowledge is used clinically to guide investment in screening and prevention, as well as being translated into new treatments. PMID- 22043046 TI - Tissue and soluble biomarkers in breast cancer and their applications: ready to use? AB - Breast cancer therapies are in continuous evolution: From surgery to hormonal therapy, from classical and new combined chemotherapies to emerging targeted agents of recent introduction to the clinic. The attempt to personalize the best treatment for each patient is driven by efficacy and safety parameters and tumor biology investigations of markers for aggressiveness and response to treatment. The plethora of targeted therapies has provided momentum for the quest to better understand not only target mechanisms of action, but also tumor behavior. Moreover, how to monitor response to these agents is crucial today to achieve better resource-sharing and to find cheaper, less invasive, and standardized detection techniques for clinically validated biomarkers. In this report, we briefly summarize data on the major tissue and soluble biomarkers focusing on their actual use in daily practice, as well as their emerging role and possible future applications in breast cancer treatment. PMID- 22043048 TI - The HER2 World: Better Treatment Selection for Better Outcome. AB - Understanding the mechanisms of trastuzumab efficacy and resistance is a step toward optimizing treatment outcome in HER2-positive breast carcinoma patients. Preclinical studies have indicated different trastuzumab antitumor mechanisms, that is, cytostatic inhibition of tumor proliferation, antibody-dependent cell cytotoxicity, and inhibition of HER2-mediated DNA repair. Clinical studies point to the clinical setting dependence of these mechanisms, with antibody-dependent cell cytotoxicity predominating when trastuzumab is used as monotherapy in neoadjuvant and metastatic settings, whereas inhibition of DNA repair predominates in neoadjuvant and adjuvant settings involving concomitant trastuzumab and chemotherapy; in sequential protocols, the antibody appears to act primarily through cytostatic activity by inhibiting HER2-mediated cell proliferation. Because the mechanisms of resistance to trastuzumab likely depend directly on those of its antitumor activity, resistance mechanisms must also be considered with respect to the different clinical settings. Moreover, the response to this reagent should be assessed according to its ability to induce tumor cytotoxic or cytostatic activity. PMID- 22043049 TI - The pathologic complete response open question in primary therapy. AB - Accurate pathological diagnosis of tumor mass before treatment and careful examination of specimens after treatment are two main objectives in the diagnostic process of neoadjuvant-treated breast cancer. To achieve the first objective, multiple core biopsies can be taken to assess intratumor heterogeneity and thus to address a more targeted therapeutic protocol. At the same time, fine needle aspiration cytology of lymph nodes found suspicious at ultrasound examination may be useful to plan surgical treatment. As for the second objective, a careful examination of specimens after primary systemic therapy is mandatory to evaluate the effect of treatment. In fact, clinical response does not necessarily correlate with pathological response. Pathological complete response (no residual invasive tumor, in situ carcinoma can be present, and no residual lymph node metastasis) constitutes an independent predictor of outcome in neoadjuvant-treated patients. Residual isolated tumor cells in primary tumor and in lymph nodes do not affect patient outcome. PMID- 22043050 TI - Surrogate markers for targeted therapy-based treatment activity and efficacy. AB - Predictive biomarkers capable of discriminating individuals who will benefit from a given therapy from those who will not are key to personalized medicine. New drugs are developed in patients with advanced disease, when ethical and practical shortcomings limit the collection of tumor specimens. The neoadjuvant setting offers a unique opportunity for overcoming these limitations. Tumor samples are collected at diagnosis and posttreatment surgery as part of a routine therapeutic approach. Pathological complete response has been consistently associated with long-term survival and may be useful as an intermediate endpoint in developing and evaluating predictive, as well as surrogate, biomarkers. In window-of opportunity studies, new drugs are administered shortly before planned surgery, and the effect of the intervention can be assessed by comparing diagnostic biopsy with the surgical specimen. Until now, clinically useful and validated predictive markers for targeted therapy are rare, but appropriate investigations in neoadjuvant studies will likely change this. PMID- 22043051 TI - Mechanisms of resistance to HER2 target therapy. AB - In the past years, several agents targeting signaling proteins critical for breast cancer growth and dissemination entered clinical evaluation. They include drugs directed against the HER/ErbB family of receptor tyrosine kinases, especially HER2; several downstream signal transducers; and proteins involved in tumor angiogenesis and dissemination. Unfortunately, resistance to targeted agents is a quite common feature, and understanding of the molecular mechanisms predicting response or failure has become a crucial issue to optimize treatment and select patients who are the best candidates to respond. The neoadjuvant setting offers unique opportunities allowing tumor sampling and search for molecular determinants of response. A variety of tumor and host factors may account for the onset of resistance. Major progress has been made in the understanding of the mechanisms involved in the primary and acquired resistance to targeted agents, especially the anti-HER2 drugs, which play a pivotal role in the weaponry against breast cancer. PMID- 22043052 TI - Predictive immunohistochemical biomarkers in the context of neoadjuvant therapy for breast cancer. AB - The adoption of personalized medicine has led to the search for prognostic and predictive markers that can be applied to individual patients to give optimal information for their clinical management. We have used samples from randomized clinical trials of hormonal and chemotherapy to identify relevant markers of sensitivity and resistance using a neoadjuvant approach by linking expression of a panel of proteins involved in growth factor receptor signaling, angiogenesis, estrogen receptor signaling, and hypoxia to individual patient response. We evaluated samples from randomized clinical trials of epirubicin with or without tamoxifen, and letrozole with or without metronomic cyclophosphamide, to study chemotherapy, hormonal therapy, and antiangiogenic effects. We present a proof of principle of this approach in identifying several key pathways that are associated with clinical and pathological response. Thus, we have shown that the hypoxia-inducible factor (HIF) pathway, mitogen activated protein kinase, and phosphorylated estrogen receptor-alpha can identify patients who are likely to respond to hormonal therapy and that HIF signaling is also a marker of resistance for anthracycline-based chemotherapy. To redress the role of HIF, we then evaluated samples from a randomized control trial of an anthracycline chemotherapy with and without erythropoietin. These studies demonstrate that the approach of using primary systemic therapy in breast can identify markers of response and potentially targets for rationale design of new therapies. PMID- 22043053 TI - Dynamic contrast-enhanced magnetic resonance imaging and blood oxygenation level dependent magnetic resonance imaging for the assessment of changes in tumor biology with treatment. AB - Functional magnetic resonance imaging (MRI) techniques are rapidly gaining importance as methods of exploring the pathophysiological properties of breast carcinomas. In the neoadjuvant setting where the primary tumor remains in situ, functional MRI is able to noninvasively evaluate microenvironmental features such as blood flow and oxygenation. Dynamic contrast-enhanced MRI provides information on tumor vascularity with evidence suggesting a role in predicting response to neoadjuvant chemotherapy. The spatial heterogeneity of response to anti angiogenic and vascular disrupting agents can also be depicted. There is preliminary data supporting blood oxygenation level-dependent MRI as a potential marker of tumor oxygenation, with the ability to characterize tissue oxygenation changes with neoadjuvant chemotherapy. Additionally, advanced MR sequences such as diffusion-weighted MRI and MR spectroscopy have the potential to provide information relating to cellularity and metabolism, respectively. PMID- 22043055 TI - Positron emission tomography and neoadjuvant therapy of breast cancer. AB - The increasing use of neoadjuvant therapy for breast cancer has led to the development of early surrogate markers of response. Positron emission tomography (PET) allows noninvasive study of fundamental biologic processes in the tumor; furthermore, PET provides various markers to assess tumor response early in the course of therapy. Numerous studies have shown that changes in tumor glucose metabolism during therapy are significantly correlated with final response and patient outcome. Moreover, new PET tracers that are currently being developed or under evaluation, providing specific information on tumor characteristics or receptor expression, will assist the development of new targeted anticancer agents. PMID- 22043054 TI - The triple-negative subtype: new ideas for the poorest prognosis breast cancer. AB - Triple-negative breast cancer accounts for about 15%-20% of all breast cancers. Patients with triple-negative subtype have a significantly increased risk of relapse and death. A panel of specific molecular alterations like high rate of p53 mutations, frequent loss of function of BRCA1, and several tyrosine kinase activations has been shown in this specific phenotype. An optimal chemotherapy regimen for these cancers remains to be determined, representing a major challenge for patient management. DNA alkylating agents, as cisplatin, were shown to be particularly effective in the neoadjuvant setting for patients with the disease. Targeted therapies are being successfully developed. Poly (ADP-ribose) polymerase-1 inhibitors induce tumor response as a single agent in BRCA1-mutated breast cancer and might sensitize cancer cells to cisplatin in the triple negative subpopulation. Chemotherapy is a cornerstone of current clinical practice for this type of disease. Progress might derive from refined biology driven phase II trials that will also integrate targeted agents with chemotherapy. PMID- 22043056 TI - Neoadjuvant chemotherapy and targeted therapies: a promising strategy. AB - Neoadjuvant therapy in breast cancer has emerged as an important setting for the development of targeted drugs. Because tumor material is available before treatment, at the moment of surgery, and possibly during treatment, precise correlations can be made between target identification, target blockade, and tumor response. Significant improvements have already been achieved by introducing targeted agents to neoadjuvant modalities. In the HER2 patient population, anti-HER2 targeted therapies have consistently demonstrated increased rates of pathological complete response. In the hormone receptor-positive setting, identifying early surrogate markers able to predict response to treatment has the potential to accelerate the development of targeted therapies. Ongoing neoadjuvant research programs such as NeoBIG and I-SPY 2 (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) are scientifically strong and will most likely demonstrate that the "neoadjuvant step" can lead directly to large, phase III adjuvant registration trials. This implies that the time between drug discovery and regulatory approval can be significantly shortened, which ultimately benefits patients. PMID- 22043058 TI - Gene profiling assay and application: the predictive role in primary therapy. AB - Several treatment options, including endocrine therapy, chemotherapy, and targeted therapy, have been shown to improve survival of breast cancer patients. Currently, clinical tests for predicting cancer response are not available, and individual markers have shown little predictive value. Several gene expression profiling studies have been carried out in the attempt to identify predictive signatures. The neoadjuvant setting revealed to be ideal for this purpose because it allows the direct assessment of response to treatment, and tumor is readily available for multiple time point biopsies. Although the results are promising, at the moment, none of these signatures has been proven to be of sufficient discriminatory power to be used in clinical setting. More effective therapies targeted to specific subsets of patients, accurate and standardized definition of therapeutic response, and properly designed clinical trials are required before microarrays can reliably be used as tools for clinical decision making. PMID- 22043057 TI - Endocrine therapy, new biologicals, and new study designs for presurgical studies in breast cancer. AB - The preoperative setting is increasingly popular for the clinical investigation of hormonal agents and new biological drugs. The effectiveness of endocrine agents is well established for estrogen receptor-positive disease, and the emphasis in preoperative studies is on their combination with agents targeted at resistance mechanisms over 3 or more months. New agents are also being assessed for early evidence of clinical efficacy in shorter-term window-of-opportunity studies. The establishment of Ki67 as an intermediate marker of treatment benefit and of long-term outcome, with endocrine drugs, provides the opportunity for new trial designs with Ki67 as the primary endpoint. The PeriOperative Endocrine Therapy for Individualizing Care (POETIC) trial is randomizing (2:1) 4000 estrogen receptor-positive patients to 2 weeks presurgical treatment with a nonsteroidal aromatase inhibitor or no presurgical treatment. It provides a unique opportunity for detailed study of the determinants of response and resistance to estrogen deprivation as well as testing the role of presurgical therapy for improved biomarker-based estimates of prognosis. PMID- 22043059 TI - New omics information for clinical trial utility in the primary setting. AB - Cancer is a complex cellular disease caused by multiple factors via genetic mutations (hereditary or somatic) or environmental factors. The emerging omics technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and interactomics, are increasingly being used for cancer research and personalized medicine; they have provided new opportunities in the molecular analysis of human cancer with unprecedented speed and detail. The omic approach has brought powerful ability to screen cancer cells at different levels from gene to metabolite and to search for novel drug targets, expounding the drug mechanism of action, identifying adverse effects in unexpected interaction, validating current drug targets, exploring potential applications for novel drugs, and enabling the translation from bench to bedside. As a clinical research tool, the neoadjuvant approach in breast cancer is the perfect setting for individualization of treatment based on clinical, pathological, image-guided, or molecular assessment, based on the omics techniques of tumors during treatment; neoadjuvant treatment offers the ability to discern treatment effect in vivo and may allow smaller trials targeting specific breast cancer subtypes. PMID- 22043060 TI - Bridging the gap between translational research and clinical application. AB - Protocols employing primary systemic therapy provide important basic knowledge about tumor behavior/response to therapy, but major challenges remain in how to obtain and use this information practically in the clinical setting. PMID- 22043061 TI - Neoadjuvant chemotherapy: early response as a guide for further treatment: clinical, radiological, and biological. AB - Neoadjuvant chemotherapy (NACT) was initially developed as a treatment strategy for patients with locally advanced breast cancer to improve operability and locoregional control. Today, NACT has become an equivalent option along with adjuvant treatment, and it is regarded as standard treatment approach for patients with locally advanced cancer because it enables breast-conserving therapy to these patients. In addition, there is increasing information on NACT in operable breast disease that supports its use in routine practice for operable tumor stages. According to the German S3 and AGO guidelines, NACT is indicated for every patient with breast cancer, who would need adjuvant chemotherapy after evaluation of radiological, histological, and clinical prognostic factors. Based on a broad range of clinical studies during the last 10 years, it has been demonstrated that NACT leads to an increasing rate of breast-conserving operations, reduced mortality, and less toxicity. A very important issue is to obtain early information about the responsiveness of the primary tumor to chemotherapy, so that individualized therapeutical strategies can be developed. The decision to proceed with NACT is depending on several considerations including surgical aspects, pretreatment diagnostic evaluations, and efficacy monitoring as well as biological aspects to predict response. PMID- 22043062 TI - Intermediate endpoints of primary systemic therapy in breast cancer patients. AB - Primary systemic therapy (PST) in breast cancer offers the opportunity to explore interactions between tumor biology and administered treatment. Changes in clinical, tissue-based, or imaging markers can provide information on the mechanisms of PST activity (activity endpoints) or predict treatment efficacy (surrogate endpoints). The most frequently used intermediate endpoint for PST is pathological complete response, but its role as a surrogate parameter of efficacy has not yet been demonstrated. Changes in tumor biology after PST may occur already a few days after treatment start; this implies that new potential surrogates occurring much earlier than pathological complete response (ie, the proliferation marker Ki67) can be identified and that short-term preoperative trials (window-of-opportunity trials) can be designed using a biological parameter as a primary endpoint. From these small trials, crucial information can be gleaned about the activity of new drugs for the design of large clinical trials. PMID- 22043063 TI - International expert consensus on primary systemic therapy in the management of early breast cancer: highlights of the Fourth Symposium on Primary Systemic Therapy in the Management of Operable Breast Cancer, Cremona, Italy (2010). AB - A panel of international breast cancer experts formulated a declaration of consensus regarding many key issues in the use of primary systemic therapy (PST) either in clinical routine or research practice. The attainment of pathological complete response (pCR), defined as no residual invasive tumor in the surgical specimens both in breast and in axillary nodes, is one of the main goals of PST, and pCR can be used as the primary objective in prospective clinical trials. However, pCR is not a reliable endpoint with all treatment approaches, and alternatives such as Ki67 index of the residual invasive disease or after 2 weeks of PST are also potential endpoints. PST has several advantages: breast conservation and the unique opportunity to obtain information on the interaction between treatment and tumor biology. Changes in tumor biology after PST are an early phenomenon; so, an additional core biopsy performed after 14 days from treatment start should be considered in clinical trials. PMID- 22043064 TI - The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations. AB - Thyroid disorders are among the most common endocrine diseases and affect virtually all physiological systems, with an especially marked impact on cardiovascular and renal systems. This review summarizes the effects of thyroid hormones on the renin-angiotensin system (RAS) and the participation of the RAS in the cardiovascular and renal manifestations of thyroid disorders. Thyroid hormones are important regulators of cardiac and renal mass, vascular function, renal sodium handling, and consequently blood pressure (BP). The RAS acts globally to control cardiovascular and renal functions, while RAS components act systemically and locally in individual organs. Various authors have implicated the systemic and local RAS in the mediation of functional and structural changes in cardiovascular and renal tissues due to abnormal thyroid hormone levels. This review analyzes the influence of thyroid hormones on RAS components and discusses the role of the RAS in BP, cardiac mass, vascular function, and renal abnormalities in thyroid disorders. PMID- 22043065 TI - Effective communication. PMID- 22043066 TI - Veterinary medical ethics. An ethicist's commentary on buying free-range eggs. PMID- 22043067 TI - Incorporation of exercise, using an underwater treadmill, and active client education into a weight management program for obese dogs. AB - Physical activity improves outcome of weight loss in obese humans, but limited information exists for dogs. Eight obese dogs (body condition score 5/5), of various breeds and genders, undertook a 3-month weight-loss program which included exercise using lead walks and underwater treadmill exercise. The median number of treadmill exercise sessions per dog was 13 (range: 5 to 17). Median distance walked per session was 0.97 km (range: 0.05 to 2.7 km) (0.6 miles; range: 0.03 to 1.70 miles) and this increased sequentially over the course of the study (P < 0.001). Mean [+/- standard deviation (s)] percentage of starting weight loss over the 3 mo was 18.9 +/- 5.44%, equivalent to a rate of weight loss of 1.5 +/- 0.43% per week. Thoracic and abdominal girth also declined significantly during the program (P < 0.0001 for both). This study demonstrates the potential benefit of including an organized exercise regimen, utilizing an underwater treadmill, in conventional canine weight management programs. PMID- 22043068 TI - A survey of intestinal parasites in dogs from Saskatoon, Saskatchewan. AB - Fresh fecal samples from 124 apparently healthy dogs and 333 random source canine fecal samples from dog walking areas were analyzed by centrifuged flotation in Sheather's solution to determine the prevalence of gastrointestinal parasites in dogs from Saskatoon, Saskatchewan. Fecal flotation was positive in 4.4% of samples. Roundworm species were found in 1.5% of samples, hookworm species were found in 0.4% of samples, whipworm species were found in 0.7%, Strongyloides spp. were found in 0.6%, Giardia spp., Cystoisospora spp., and Alaria spp. were found in 0.4% of samples. PMID- 22043069 TI - Clinical evaluation of a single daily dose of phenylpropanolamine in the treatment of urethral sphincter mechanism incompetence in the bitch. AB - The objective of this retrospective study was to determine the efficacy of a single daily oral dose of phenylpropanolamine (PPA) in the treatment of urethral sphincter mechanism incompetence (USMI) in bitches. Nine bitches diagnosed with USMI were treated with a single daily dose [1.5 mg/kg body weight (BW)] of PPA for at least 1 month. Urethral pressure profiles (UPP) were performed in 7 dogs before treatment and repeated in 4 of them after treatment. Treatment with PPA resulted in long-term continence in 8/9 bitches. One dog did not respond to PPA and was treated surgically later. Recheck UPPs showed a significant increase in maximal urethral closure pressure in the 4 bitches after treatment with PPA compared to before treatment. In conclusion, long-term continence can be achieved in bitches affected with USMI after administration of a single daily dose of PPA (1.5 mg/kg BW). PMID- 22043070 TI - Insulin-dependent diabetes mellitus associated with presumed autoimmune polyendocrine syndrome in a mare. AB - A 5-year-old Thoroughbred-cross mare was diagnosed with insulin-dependent diabetes mellitus. Partial glycemic control and clinical improvement were achieved with daily insulin administration for 18 mo. The mare subsequently developed evidence of hypoadrenocorticism and died. Necropsy findings included lymphocytic infiltration of the pancreas, adrenal cortex, adrenal medulla, and thyroid glands, suggestive of an immune-mediated polyendocrinopathy. PMID- 22043071 TI - Submandibular lymph node abscess caused by Actinomyces denticolens in a horse in Ontario. AB - This is the first report of the isolation of Actinomyces denticolens, an opportunistic pathogen, from a draining submandibular lymph node abscess in a horse in Ontario. Due to the similarity of the clinical signs with strangles, this pathogen should be included in the differential diagnosis of submandibular lymphadenopathy in the horse. PMID- 22043072 TI - Proximal mandibular nerve block, using electrolocation, for rostral mandibulectomy in a geriatric dog. AB - We describe a case of proximal mandibular nerve block with ropivacaine, using electrolocation, for perioperative pain management in a geriatric dog undergoing rostral mandibulectomy. The patient did not require intraoperative analgesia or analgesic supplementation for 8 h after the end of the surgery. PMID- 22043073 TI - Trauma resulting in hemarthrosis and long medial collateral ligament desmitis of the tarsocrural joint in a horse. AB - A horse was initially diagnosed with hemarthrosis and desmitis of the long medial collateral ligament of the right tarsus and later developed prominent enthesiophytosis at the site of insertion of the ligament's deep portion. Hemarthrosis due to intra- or peri-articular pathology can cause recurrent lameness, even without evident external trauma. PMID- 22043074 TI - Clinical outcome of calves with failure of passive transfer as diagnosed by a commercially available IgG quick test kit. AB - The efficacy of an IgG quick test in detecting calves with failure of passive transfer was assessed. The test was carried out on 97 male calves, 38% of which were negative (IgG < 10 mg/mL). Morbidity and mortality due to infectious diseases were significantly higher in the negative group showing that the quick test is useful in identifying calves more susceptible to infectious disease. PMID- 22043075 TI - Seroprevalence of Borrelia burgdorferi, Anaplasma phagocytophilum, Ehrlichia canis, and Dirofilaria immitis among dogs in Canada. AB - The seropositivity of dogs to Borrelia burgdorferi, Anaplasma phagocytophilum, and Ehrlichia canis antibodies, and Dirofilaria immitis antigen was assessed in Canada. Borrelia burgdorferi had the highest seroprevalence, while that of Dirofilaria immitis has not changed significantly in the past 20 y. The risk for these vector-borne infectious agents in Canadian dogs is low but widespread with foci of higher prevalence. PMID- 22043076 TI - The efficacy of pour-on ivermectin in bison (Bison bison). AB - To test the effectiveness of pour-on ivermectin in parasitized bison, changes in fecal parasite egg counts after treatment with ivermectin injectable or pour-on preparations were compared to a negative control group. There was no difference between the two ivermectin groups, and both forms of ivermectin were effective in reducing fecal parasite egg counts in parasitized bison. PMID- 22043077 TI - A case of biphasic mesothelioma with osseous and chondromatous differentiation in a cat. AB - An 11-year-old domestic short hair cat with dyspnea, cyanosis, and pleural effusion died. Necropsy revealed several nodules and masses on the parietal pleura, pericardium, and diaphragm. The tumor contained epithelial and mesenchymal components and displayed osseous and chondromatous differentiation. Tumors cells were positive for pancytokeratin and vimentin. This is the first report of a biphasic mesothelioma with osseous and chondromatous differentiation in this species. PMID- 22043078 TI - Granulocytic anaplasmosis in a horse from Nova Scotia caused by infection with Anaplasma phagocytophilum. AB - A 16-year-old Paint stallion was presented with intermittent fever, inappetance, lethargy, icterus, distal limb edema, and submandibular lymphadenopathy. The horse was native to Nova Scotia and had never left that province. Morulae were detected in granulocytes. Ananaplasma phagocytophilum infection was confirmed by serology and polymerase chain reaction (PCR). The horse responded to treatment with oxytetracycline. PMID- 22043079 TI - A case of valvular pulmonic stenosis and an aberrant coronary artery in a Brittany spaniel. AB - Valvular pulmonic stenosis and aberrancy of the right coronary artery with subsequent subvalvular stenosis was found on echocardiographic evaluation of a 9 month-old Brittany spaniel. Previous echocardiography at 4 mo of age revealed the pulmonic stenosis; however, the aberrant coronary artery only became apparent during the second evaluation. PMID- 22043080 TI - Genetic engineering of animals: ethical issues, including welfare concerns. PMID- 22043081 TI - Lifestyle improvements call for reduction in full-time equivalent status. PMID- 22043082 TI - Multiple pyogranulomas in a Katahdin ewe. PMID- 22043083 TI - Strain Hardening and Strain Softening of Reversibly Cross-linked Supramolecular Polymer Networks. AB - The large amplitude oscillatory shear behavior of metallo-supramolecular polymer networks formed by adding bis-Pd(II) cross-linkers to poly(4-vinylpyridine) (PVP) in dimethyl sulfoxide (DMSO) solution is reported. The influence of scanning frequency, dissociation rate of cross-linkers, concentration of cross-linkers, and concentration of PVP solution on the large amplitude oscillatory shear behavior is explored. In semidilute unentangled PVP solutions, above a critical scanning frequency, strain hardening of both storage moduli and loss moduli is observed. In the semidilute entangled regime of PVP solution, however, strain softening is observed for samples with faster cross-linkers (k(d) ~ 1450 s(-1)), whereas strain hardening is observed for samples with slower cross-linkers (k(d) ~ 17 s(-1)). The mechanism of strain hardening is attributed primarily to a strain-induced increase in the number of elastically active chains, with possible contributions from non-Gaussian stretching of polymer chains at strains approaching network fracture. The divergent strain softening of samples with faster cross-linkers in semidilute entangled PVP solutions, relative to the strain hardening of samples with slower cross-linkers, is consistent with observed shear thinning/shear thickening behavior reported previously and is attributed to the fact that the average time that a cross-linker remains detached is too short to permit the local relaxation of polymer chain segments that is necessary for a net conversion of elastically inactive to elastically active cross-linkers. These and other observations paint a picture in which strain softening and shear thinning arise from the same set of molecular mechanisms, conceptually uniting the two nonlinear responses for this system. PMID- 22043092 TI - The national prevention strategy: shifting the nation's health-care system. PMID- 22043093 TI - Identification of structural interventions for HIV/AIDS prevention: the concept mapping exercise. AB - Structural interventions have been defined as those prevention interventions that include physical, social, cultural, organizational, community, economic, legal, and policy factors. In an effort to examine the feasibility, evaluability, and sustainability of structural interventions for HIV prevention, the Centers for Disease Control and Prevention implemented a project that involved asking experts in HIV prevention and other areas of public health-including injury and violence prevention, tobacco control, drug abuse, and nutrition-to provide input on the identification of structural interventions based on the aforementioned definition. The process resulted in a list of 123 interventions that met the definition. The experts were asked to group these interventions into categories based on similarity of ideas. They were also asked to rate these interventions in terms of impact they would have, if implemented, on reducing HIV transmission. The findings highlight the need for conducting further research on structural interventions, including feasibility of implementation and effectiveness of reducing HIV transmission risks. PMID- 22043094 TI - Exploring geographic variation in lung cancer incidence in Kentucky using a spatial scan statistic: elevated risk in the Appalachian coal-mining region. AB - OBJECTIVES: We examined geographic patterns of lung cancer incidence in Kentucky. Recent research has suggested that the coal-mining industry contributes to lung cancer risk in Appalachia. We focused on the southeastern portion of the state, which has some of the highest lung cancer rates in the nation. METHODS: We implemented a spatial scan statistic to identify areas with lung cancer incidence rates that were higher than expected, after adjusting for age, gender, and smoking. The Kentucky Cancer Registry supplied information on cases (1995-2007). The U.S. Census (2000) and several years of Behavioral Risk Factor Surveillance System data (1996-2006) provided county-level population and smoking data. We compared the results with coal-mining data from the Mining Safety and Health Administration and public water utility data from the Kentucky Division of Water. RESULTS: We identified three clusters of counties with higher-than-expected rates. Cluster 1 (relative risk [RR] = 1.21, p<0.01) included 12 counties in southeastern Kentucky. Cluster 2 (RR=1.17, p<0.01) included three nearby counties in the same region. Several of the 15 counties in Cluster 3 (RR=1.04, p=0.01) were part of the Louisville, Kentucky, or Cincinnati, Ohio, metropolitan areas. All of the counties in Clusters 1 and 2 produced significant amounts of coal. CONCLUSION: Environmental exposures related to the coal-mining industry could contribute to the high incidence of lung cancer in southeastern Kentucky. Lack of evidence for this effect in western Kentucky could be due to regional differences in mining practices and access to public water utilities. Future research should collect biological specimens and environmental samples to test for the presence of trace elements and other lung carcinogens. PMID- 22043095 TI - Adverse birth outcomes among nulliparous vs. multiparous women. AB - OBJECTIVES: Previous studies indicate that nulliparous women (i.e., women having no previous births) are at higher risk for adverse birth outcomes than multiparous women (i.e., women having had at least one previous birth). We examined whether part of the difference in adverse outcome rates is attributable to nulliparous women with poor pregnancy outcomes being less likely (through choice or fecundity differences) to have a subsequent live birth within the same time period as nulliparous women without adverse outcomes. METHODS: Using deterministic matching, we linked nulliparous women from the North Carolina Detailed Birth Record to subsequent births. We employed statistical and simulation-based analyses to estimate first birth outcome rate differences between nulliparous women who did have a subsequent live birth vs. those who did not. Our Markov simulations focused on preterm birth (PTB). RESULTS: Among nulliparous women who were not linked to a second birth, maternal age-adjusted rates of multiple adverse outcomes were all statistically higher compared with rates for linked women. These results also held in race/ethnicity-specific analyses. Simulations found that the relative risk of PTB associated with a history of PTB was underestimated if some women who would have been at risk for PTB did not experience a second birth. CONCLUSIONS: The observed differences in rates of adverse outcomes between nulliparous and multiparous women are partly attributable to higher-risk women not having a subsequent live birth, either by choice or due to fecundity differences. PMID- 22043096 TI - Breast and cervical cancer screening patterns among American Indian women at IHS clinics in Montana and Wyoming. AB - OBJECTIVES: We investigated factors associated with primary and secondary breast and cervical cancer screening among American Indian (AI) women receiving care from the Indian Health Service (IHS) in Montana and Wyoming. METHODS: Rates of primary screening (i.e., screening without evidence of a prior abnormal) and secondary screening during a three-year period (2004-2006) were determined in an age- and clinic-stratified random sample of 1,094 women at six IHS units through medical record review. RESULTS: Three-year mammography prevalence rates among AI women aged >=45 years were 37.7% (95% confidence interval [CI] 34.1, 41.3) for primary and 58.7% (95% CI 43.9, 73.5) for secondary screening. Among women aged >=18 years, three-year Pap test prevalence rates were 37.8% (95% CI 34.9, 40.6) for primary and 53.2% (95% CI 46.0, 60.4) for secondary screening. Primary mammography screening was positively associated with number of visits and receiving care at an IHS hospital (both p<0.001). Primary Pap test screening was inversely associated with age and positively associated with the number of patient visits (both p<0.001). Secondary mammography screening was inversely associated with driving distance to an IHS facility (p=0.035). CONCLUSION: Our results are consistent with other surveys among AI women, which report that Healthy People 2010 goals for breast (90%) and cervical (70%) cancer screening have not been met. Improvements in breast and cervical cancer screening among AI women attending IHS facilities are needed. PMID- 22043097 TI - Changing trends in viral hepatitis-associated hospitalizations in the American Indian/Alaska Native population, 1995-2007. AB - OBJECTIVE: We described the changing epidemiology of viral hepatitis among the American Indian/Alaska Native (AI/AN) population that uses Indian Health Service (IHS) health care. METHODS: We used hospital discharge data from the IHS National Patient Information Reporting System to determine rates of hepatitis A-, B-, and C-associated hospitalization among AI/ANs using IHS health care from 1995-2007 and summary periods 1995-1997 and 2005-2007. RESULTS: Hepatitis A-associated hospitalization rates among AI/AN people decreased from 4.9 per 100,000 population during 1995-1997 to 0.8 per 100,000 population during 2005-2007 (risk ratio [RR] = 0.2, 95% confidence interval [CI] 0.1, 0.2). While there was no significant change in the overall hepatitis B-associated hospitalization rate between time periods, the average annual rate in people aged 45-64 years increased by 109% (RR=2.1, 95% CI 1.4, 3.2). Between the two time periods, the hepatitis C-associated hospitalization rate rose from 13.0 to 55.0 per 100,000 population (RR=4.2, 95% CI 3.8, 4.7), an increase of 323%. The hepatitis C associated hospitalization rate was highest among people aged 45-64 years, males, and those in the Alaska region. CONCLUSIONS: Hepatitis A has decreased to near eradication levels among the AI/AN population using IHS health care. Hepatitis C associated hospitalizations increased significantly; however, there was no significant change in hepatitis B-associated hospitalizations. Emphasis should be placed on continued universal childhood and adolescent hepatitis B vaccination and improved vaccination of high-risk adults. Prevention and education efforts should focus on decreasing hepatitis C risk behaviors and identifying people with hepatitis C infection so they may be referred for treatment. PMID- 22043098 TI - Smoke-free laws, gender, and reduction in hospitalizations for acute myocardial infarction. AB - OBJECTIVE: We examined gender differences in the incidence of acute myocardial infarction (AMI) after the passage of a smoke-free law in Lexington, Kentucky. The initial legislation had exemptions not covering manufacturing facilities and government buildings, which may have put men at greater risk for AMI. METHODS: We examined the effect of Lexington's smoke-free public places law on hospitalizations for AMI (i.e., heart attack) among men and women 40 months prior to and 32 months after enactment of the law. We used the statewide administrative database (Comp Data) for all hospital billing records for the four health-care systems in Lexington-Fayette County. Cases were included in the analysis if (1) the patient was $35 years of age; (2) the patient had a primary discharge diagnosis of AMI, with an International Classification of Diseases, Ninth Revision code in the range of 410.00 to 410.99; and (3) the date of service was between January 1, 2001, and December 31, 2006. RESULTS: Among women, AMI hospitalizations declined 23% after the law took effect. The rate of AMI events among men did not change significantly. There was an overrepresentation of women in the hospitality industry and a disproportionate number of men working in manufacturing facilities and government worksites not mandated by the law. CONCLUSIONS: We found gender differences in the reduction of AMI hospitalizations following implementation of a smoke-free law that covered only some sectors of the workforce. Enacting smoke-free laws that cover all places of employment and strengthening existing partial laws may extend protection against AMIs to female and male workers. PMID- 22043100 TI - Wild mushroom exposures in Florida, 2003-2007. AB - OBJECTIVE: Exposure to wild mushrooms can lead to serious illness and death. However, there is little information on the epidemiology of mushroom exposures nationwide, as there is no specific surveillance for this outcome. We described mushroom exposures in Florida using available data sources. METHODS: We performed a population-based study of mushroom exposure calls to the Florida Poison Information Center Network (FPICN) and cases of mushroom poisoning reported in hospital inpatient and emergency department (ED) data from 2003 through 2007. RESULTS: There were 1,538 unduplicated mushroom exposures reported during this period, including 1,355 exposure calls and 428 poisoning cases. Most exposures reported to FPICN occurred in children <=6 years of age (45%) and males (64%), and most were unintentional ingestions (60%). Many exposures resulted in no effect (35%), although 21% reported mild symptoms that resolved rapidly, 23% reported prolonged/systemic (moderate) symptoms, and 1% reported life-threatening effects. Most calls occurred when in or en route to a health-care facility (43%). More than 71% of poisonings identified in hospital records were managed in an ED, and most occurred in young adults 16-25 years of age (49%), children <=6 years of age (21%), adults >25 years of age (21%), and males (70%). No deaths were reported. CONCLUSIONS: Combined, these data were useful for describing mushroom exposures. Most exposures occurred in males and in young children (<=6 years of age) and young adults (16-25 years of age), with 78% resulting in contact with a health-care facility. Education should target parents of young children especially during summer, when mushrooms are more abundant-and young adults who are likely experimenting with mushrooms for their potential hallucinogenic properties. PMID- 22043099 TI - Black-white differences in self-reported disability outcomes in the U.S.: early childhood to older adulthood. AB - OBJECTIVE: We examined black-white differences in activities of daily living (ADLs), functional limitations (FLs), vision/hearing/sensory impairment, and memory/learning problems in a large, nationally representative sample of community-dwelling and institutionalized people across the lifespan. METHODS: Data are from the 2006 American Community Survey (n=2,288,800). We included data on non-Hispanic black respondents (125,985 males and 145,780 females) and non Hispanic white respondents (977,792 males and 1,039,243 females) >=5 years of age. We used logistic regression to examine the black-white odds for each disability outcome. The overall response rate was 97.5%. RESULTS: For FLs, ADL limitations, and memory/learning problems, black people experienced higher odds of disability across the adult lifespan compared with white people. Black-white differences narrowed in older age. For vision/hearing problems, a black-white crossover was found in older age (>=85 years), where odds of vision/hearing problems were lower among black people than among white people. For all disability outcomes, black-white differences peaked in midlife (50-69 years of age), with black people having approximately 1.5 to two times the odds of disabilities as their white peers. CONCLUSIONS: The study findings suggest the need to address black-white disparities across a range of disability outcomes throughout the lifespan. Future work identifying the factors accounting for this pattern of disparities will help inform the development of appropriate prevention strategies. PMID- 22043101 TI - Adverse respiratory symptoms and environmental exposures among children and adolescents following Hurricane Katrina. AB - OBJECTIVES: Children and adolescents are especially vulnerable to environmental exposures and their respiratory effects. Following Hurricane Katrina in 2005, residents experienced multiple adverse environmental exposures. We characterized the association between upper respiratory symptoms (URS) and lower respiratory symptoms (LRS) and environmental exposures among children and adolescents affected by Hurricane Katrina. METHODS: We conducted a cross-sectional study following the return of the population to New Orleans after Hurricane Katrina (October 2005 and February 2006) among a convenience sample of children and adolescents attending New Orleans health facilities. We used uni-, bi-, and multivariable analyses to describe participants, exposures, and associations with URS/LRS. RESULTS: Of 1,243 participants, 47% were Caucasian, 50% were male, and 72% were younger than 11 years of age. Multiple environmental exposures were identified during and after the storm and at current residences: roof/glass/storm damage (50%), outside mold (22%), dust (18%), and flood damage (15%). Self reported URS and LRS (76% and 36%, respectively) were higher after the hurricane than before the hurricane (22% and 9%, respectively, p<0.0001). Roof/glass/storm damage at home was associated with URS (adjusted odds ratio [AOR] = 1.59, 95% confidence interval [CI] = 1.15, 2.21) and LRS (AOR=1.35, 95% CI 1.01, 1.80), while mold growth at home was associated with LRS (AOR=1.47, 95% CI 1.02, 2.12). CONCLUSIONS: Children and adolescents affected by Hurricane Katrina experienced environmental exposures associated with increased prevalence of reported URS and LRS. Additional research is needed to investigate the long-term health impacts of Hurricane Katrina. PMID- 22043102 TI - Increased fall-related mortality rates in New Mexico, 1999-2005. AB - OBJECTIVE: In 2000, fall injuries affected 30% of U.S. residents aged >=65 years and cost $19 billion. In 2005, New Mexico (NM) had the highest fall-related mortality rate in the United States. We described factors associated with these elevated fall-related mortality rates. METHODS: To better understand the epidemiology of fatal falls in NM, we used state and national (Web-based Injury Statistics Query and Reporting System) vital records data for 1999-2005 to identify unintentional falls that were the underlying cause of death. We calculated age-adjusted mortality rates, rate ratios (RRs), and 95% confidence intervals (CIs) by sex, ethnicity, race, and year. RESULTS: For 1999-2005 combined, NM's fall-related mortality rate (11.7 per 100,000 population) was 2.1 times higher than the U.S. rate (5.6 per 100,000 population). Elevated RRs persisted when stratified by sex (male RR=2.0, female RR=2.2), ethnicity (Hispanic RR=2.5, non-Hispanic RR=2.1), race (white RR=2.0, black RR=1.7, American Indian RR=2.3, and Asian American/Pacific Islander RR=3.1), and age (>=50 years RR=2.0, <50 years RR=1.2). Fall-related mortality rates began to increase exponentially at age 50 years, which was 15 years younger than the national trend. NM non-Hispanic individuals had the highest demographic-specific fall-related mortality rate (11.8 per 100,000 population, 95% CI 11.0, 12.5). NM's 69.5% increase in fall-related mortality rate was approximately twice the U.S. increase (31.9%); the increase among non-Hispanic people (86.2%) was twice that among Hispanic people (43.5%). CONCLUSIONS: NM's fall-related mortality rate was twice the U.S. rate; exhibited a greater increase than the U.S. rate; and persisted across sex, ethnicity, and race. Fall-related mortality disproportionately affects a relatively younger population in NM. Characterizing fall etiology will assist in the development of effective prevention measures. PMID- 22043103 TI - Veterinary public health capacity in the United States: opportunities for improvement. AB - OBJECTIVES: In 2006, the Association of American Veterinary Medical Colleges reported that the shortage (>= 1,500) of public health veterinarians is expected to increase tenfold by 2020. In 2008, the Centers for Disease Control and Prevention (CDC) Preventive Medicine Fellows conducted a pilot project among CDC veterinarians to identify national veterinary public health workforce concerns and potential policy strategies. METHODS: Fellows surveyed a convenience sample (19/91) of public health veterinarians at CDC to identify veterinary workforce recruitment and retention problems faced by federal agencies; responses were categorized into themes. A focus group (20/91) of staff veterinarians subsequently prioritized the categorized themes from least to most important. Participants identified activities to address the three recruitment concerns with the highest combined weight. RESULTS: Participants identified the following three highest prioritized problems faced by federal agencies when recruiting veterinarians to public health: (1) lack of awareness of veterinarians' contributions to public health practice, (2) competitive salaries, and (3) employment and training opportunities. Similarly, key concerns identified regarding retention of public health practice veterinarians included: (1) lack of recognition of veterinary qualifications, (2) competitive salaries, and (3) seamless integration of veterinary and human public health. CONCLUSIONS: Findings identified multiple barriers that can affect recruitment and retention of veterinarians engaged in public health practice. Next steps should include replicating project efforts among a national sample of public health veterinarians. A committed and determined long-term effort might be required to sustain initiatives and policy proposals to increase U.S. veterinary public health capacity. PMID- 22043105 TI - Accountable care organizations. PMID- 22043107 TI - Incorporating tuberculosis content into public health core curricula: the TB curriculum development project. PMID- 22043108 TI - The relationship between local food sources and open space to body mass index in urban children. PMID- 22043109 TI - Manganese-based MRI contrast agents: past, present and future. AB - Paramagnetic and superparamagnetic metals are used as contrast materials for magnetic resonance (MR) based techniques. Lanthanide metal gadolinium (Gd) has been the most widely explored, predominant paramagnetic contrast agent until the discovery and association of the metal with nephrogenic systemic fibrosis (NSF), a rare but serious side effects in patients with renal or kidney problems. Manganese was one of the earliest reported examples of paramagnetic contrast material for MRI because of its efficient positive contrast enhancement. In this review, manganese based contrast agent approaches are discussed with a particular emphasis on their synthetic approaches. Both small molecules based typical blood pool contrast agents and more recently developed novel nanometer sized materials are reviewed focusing on a number of successful molecular imaging examples. PMID- 22043110 TI - Hydrogen-bonding 2D metal-organic solids as highly robust and efficient heterogeneous green catalysts for Biginelli reaction. AB - Two new Zn(II) and Cd(II) MOFs have been synthesized. These MOFs have been applied as heterogeneous catalysts for the green synthesis of a variety of dihydropyrimidinone derivatives through the Biginelli reaction and the desired products were obtained in high yields with short reaction time under mild solvent free conditions. Moreover, the MOF catalysts may be readily recovered after the reaction and reused for many cycles. PMID- 22043111 TI - Genetic underpinnings of obstructive sleep apnea: are we making progress? PMID- 22043112 TI - Searching for the missing heritability. PMID- 22043113 TI - Back to the future or forward to the past? PMID- 22043114 TI - Are short bad sleep nights a hindrance to a healthy heart? PMID- 22043115 TI - Toward a multi-level approach to CPAP adherence. PMID- 22043116 TI - A review of genetic association studies of obstructive sleep apnea: field synopsis and meta-analysis. AB - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a multifactorial disorder with a heritable component. We performed a field synopsis of genetic association studies of OSA to synthesize the available evidence. DESIGN: Systematic literature review and meta-analysis. SETTING: Genetic association studies. PATIENTS OR PARTICIPANTS: We searched multiple databases to identify studies of non-HLA genetic associations in OSA. We assessed the power of the primary studies to identify odds ratios (OR) in a plausible range and performed random effects meta-analyses for genetic associations investigated by at least 3 studies. We explored the consistency of the findings between population- and family-based studies. INTERVENTIONS: None MEASUREMENTS AND RESULTS: We identified a total of 31 population-based case-control studies reporting allele-frequency data on 48 polymorphism-OSA associations. Sample sizes were generally small (median number of cases = 102, 25th-75th percentile = 55-151; median number of controls = 79, 25th-75th percentile = 58-137), and genetic effects were moderate in magnitude (median OR = 1.15, 25th-75th percentile = 0.89-1.40). Studies were severely underpowered to detect ORs as high as 2; only eight comparisons (in 6 studies) had more than 90% power to identify a genetic effect of that magnitude at its current sample size. Four genetic associations had been investigated in >= 3 studies: TNFA (-308 A/G) rs1800629, ACE I/D, APOE epsilon2, and APOE epsilon4. Only TNFA rs1800629 was significantly associated with OSA under an allele frequency model (3 studies, odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.26-2.61). These results were robust to alternative genetic models; findings for APOE variants were consistent with those from family-based studies. CONCLUSIONS: The developing field of OSA genetics is currently dominated by small and underpowered investigations. Promising findings regarding TNFA rs1800629 need to be replicated in larger studies using more comprehensive genotyping methods. PMID- 22043117 TI - Identification of causal genes, networks, and transcriptional regulators of REM sleep and wake. AB - STUDY OBJECTIVE: Sleep-wake traits are well-known to be under substantial genetic control, but the specific genes and gene networks underlying primary sleep-wake traits have largely eluded identification using conventional approaches, especially in mammals. Thus, the aim of this study was to use systems genetics and statistical approaches to uncover the genetic networks underlying 2 primary sleep traits in the mouse: 24-h duration of REM sleep and wake. DESIGN: Genome wide RNA expression data from 3 tissues (anterior cortex, hypothalamus, thalamus/midbrain) were used in conjunction with high-density genotyping to identify candidate causal genes and networks mediating the effects of 2 QTL regulating the 24-h duration of REM sleep and one regulating the 24-h duration of wake. SETTING: Basic sleep research laboratory. PATIENTS OR PARTICIPANTS: Male [C57BL/6J * (BALB/cByJ * C57BL/6J*) F1] N(2) mice (n = 283). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The genetic variation of a mouse N2 mapping cross was leveraged against sleep-state phenotypic variation as well as quantitative gene expression measurement in key brain regions using integrative genomics approaches to uncover multiple causal sleep-state regulatory genes, including several surprising novel candidates, which interact as components of networks that modulate REM sleep and wake. In particular, it was discovered that a core network module, consisting of 20 genes, involved in the regulation of REM sleep duration is conserved across the cortex, hypothalamus, and thalamus. A novel application of a formal causal inference test was also used to identify those genes directly regulating sleep via control of expression. CONCLUSION: Systems genetics approaches reveal novel candidate genes, complex networks and specific transcriptional regulators of REM sleep and wake duration in mammals. PMID- 22043118 TI - Treating obstructive sleep apnea with hypoglossal nerve stimulation. AB - BACKGROUND: Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity. STUDY OBJECTIVES: To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA. PARTICIPANTS: Twenty-one patients, 67% male, age (mean +/- SD) 53.6 +/- 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP). DESIGN: Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI). RESULTS: HGNS was used on 89% +/- 15% of nights (n = 21). On these nights, it was used for 5.8 +/- 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 +/- 17.5 to 19.5 +/- 16.7), ESS (12.1 +/- 4.7 to 8.1 +/- 4.4), FOSQ (14.4 +/- 2.0 to 16.7 +/- 2.2), SAQLI (3.2 +/- 1.0 to 4.9 +/- 1.3), and BDI (15.8 +/- 9.0 to 9.7 +/- 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement. CONCLUSIONS: HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA associated symptoms. CLINICAL TRIAL INFORMATION: NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea. REGISTRATION NUMBER: NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926. PMID- 22043119 TI - Sleep duration and sleep quality in relation to 12-year cardiovascular disease incidence: the MORGEN study. AB - STUDY OBJECTIVES: We studied sleep duration and sleep quality in relation to cardiovascular disease (CVD) incidence. DESIGN/SETTING: Dutch population-based cohort study. PARTICIPANTS: 20,432 men and women aged 20-65 and with no history of CVD. INTERVENTIONS: N/A. MEASUREMENTS: Sleep duration and sleep quality were assessed by a self-administered questionnaire. Morbidity data, vital status, and causes of death were obtained through linkage with several national registries. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated using Cox proportional hazards models. RESULTS: During 10-15 years of follow-up, 1,486 CVD and 1,148 coronary heart disease (CHD) events occurred. Short sleepers (<= 6 h) had a 15% higher risk of total CVD (HR: 1.15; 95%CI: 1.00-1.32) and a 23% higher risk of CHD (HR: 1.23 [1.04-1.45]) compared to normal sleepers (7 h) after adjustment for all confounders. Additional adjustment for intermediate biological risk factors attenuated these relative risks to 1.11 (0.97-1.27) for total CVD and to 1.19 (1.00-1.40) for CHD. Short sleepers with poor sleep quality had a 63% higher risk of CVD (HR: 1.63 [1.21-2.19]) and a 79% higher risk of CHD incidence (HR: 1.79 [1.24-2.58]) compared to normal sleepers with good sleep quality, after adjustments for all confounders. We observed no associations between long sleep duration (>= 9 h) and CVD or CHD incidence. CONCLUSIONS: Short sleepers, especially those with poor sleep quality, have an increased risk of total CVD and CHD incidence. Future investigations should not only focus on sleep duration, but should also take sleep quality into account. PMID- 22043120 TI - Poor sleep quality is associated with preterm birth. AB - STUDY OBJECTIVES: Preterm birth (PTB) is a major public health priority and the most common adverse pregnancy outcome. Several risk factors have been identified, but a gap in the understanding of the underlying etiology of PTB persists. Poor sleep quality is a correlate of adverse health outcomes. Therefore, we evaluated whether sleep quality during pregnancy was a clinically relevant risk factor for PTB. DESIGN: Observational. MEASUREMENTS AND RESULTS: Participants included 166 pregnant women (mean age = 28.6 +/- 5.5 years). Self-report questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), were administered at 14-16, 24-26, and 30-32 weeks gestation. Logistic regression models were used to evaluate whether sleep quality was associated with preterm delivery. Poor sleep quality was a predictor of preterm birth, with the largest effects in early pregnancy (14-16 weeks) (OR: 1.25 95% CI [1.04-1.50], P = 0.02) and more modest effects in later pregnancy (30-32 weeks) (OR: 1.18 95% CI [0.98-1.42], P = 0.07). With every one-point increase on the PSQI, the odds of preterm birth increase 25% in early pregnancy and 18% in later pregnancy. CONCLUSIONS: Poor sleep quality, in both early and late pregnancy, is associated with an increased risk of delivering preterm. Currently the specific pathway(s) through which disturbed sleep contributes to PTB are unknown. We suggest that poor sleep may contribute to increased risk for PTB both independently, as well as in conjunction with other established risk factors, such as stress. PMID- 22043121 TI - Poor sleep quality predicts deficient emotion information processing over time in early adolescence. AB - STUDY OBJECTIVES: There is deepening understanding of the effects of sleep on emotional information processing. Emotion information processing is a key aspect of social competence, which undergoes important maturational and developmental changes in adolescence; however, most research in this area has focused on adults. Our aim was to test the links between sleep and emotion information processing during early adolescence. DESIGN: Sleep and facial information processing were assessed objectively during 3 assessment waves, separated by 1 year lags. SETTING: Data were obtained in natural environments-sleep was assessed in home settings, and facial information processing was assessed at school. PARTICIPANTS: 94 healthy children (53 girls, 41 boys), aged 10 years at Time 1. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Facial information processing was tested under neutral (gender identification) and emotional (emotional expression identification) conditions. Sleep was assessed in home settings using actigraphy for 7 nights at each assessment wave. Waking > 5 min was considered a night awakening. Using multilevel modeling, elevated night awakenings and decreased sleep efficiency significantly predicted poor performance only in the emotional information processing condition (e.g., b = -1.79, SD = 0.52, confidence interval: lower boundary = -2.82, upper boundary = -0.076, t(416.94) = -3.42, P = 0.001). CONCLUSIONS: Poor sleep quality is associated with compromised emotional information processing during early adolescence, a sensitive period in socio emotional development. PMID- 22043122 TI - The Childhood Adenotonsillectomy Trial (CHAT): rationale, design, and challenges of a randomized controlled trial evaluating a standard surgical procedure in a pediatric population. AB - Each year, over 500,000 adenotonsillectomies (AT), mostly for the treatment of pediatric obstructive sleep apnea (OSA) are performed in the US in children under 15 years of age. No definitive study, however, has been yet conducted that has rigorously evaluated the effectiveness of AT for not only improving sleep disordered breathing, but also for improving clinically relevant outcomes, such as neurocognitive function, behavior, and quality of life. The Childhood Adenotonsillectomy Trial (CHAT) was designed to assess neuropsychological and health outcomes in children randomized to receive early AT (eAT) as compared to Watchful Waiting with Supportive Care (WWSC). Important secondary goals of the study are to evaluate outcomes in subgroups defined by obesity and race. This paper addresses key elements in the design and implementation of a controlled trial for a widely used "standard practice" surgical intervention in a pediatric population, that include establishment of standardized data collection procedures across sites for a wide variety of data types, establishment of equipoise, and approaches for minimizing unblinding of selected key personnel. The study framework that was established should provide a useful template for other pediatric controlled studies or other studies that evaluate surgical interventions. PMID- 22043123 TI - Loneliness is associated with sleep fragmentation in a communal society. AB - STUDY OBJECTIVE: Loneliness has been shown to predict poor health. One hypothesized mechanism is that lonely individuals do not sleep as well as individuals who feel more connected to others. Our goal was to test whether loneliness is associated with sleep fragmentation or sleep duration. DESIGN: Cross-sectional study. SETTING: Members of a traditional, communal, agrarian society living in South Dakota. PARTICIPANTS: Ninety-five participants (mean age 39.8 years, 55% female) who were >= 19 years of age at the study's inception. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: We conducted interviews querying loneliness, depression, anxiety, and stress, as well as subjective sleep quality and daytime sleepiness. Study participants wore a wrist actigraph for one week to measure objective sleep properties; the two studied here were sleep fragmentation and sleep duration. Higher loneliness scores were associated with significantly higher levels of sleep fragmentation (beta = 0.073, t = 2.55, P = 0.01), controlling for age, sex, body mass index, risk of sleep apnea, and negative affect (a factor comprising symptoms of depression and anxiety, and perceived stress). Loneliness was not associated with sleep duration or with either subjective sleep measure. CONCLUSIONS: Loneliness was a significant predictor of sleep fragmentation. Humans' social nature may partly be manifest through our dependence on feeling secure in our social environment to sleep well. PMID- 22043124 TI - State-dependent changes in cortical gain control as measured by auditory evoked responses to varying intensity stimuli. AB - STUDY OBJECTIVES: Auditory evoked potential (AEP) components correspond to sequential activation of brain structures within the auditory pathway and reveal neural activity during sensory processing. To investigate state-dependent modulation of stimulus intensity response profiles within different brain structures, we assessed AEP components across both stimulus intensity and state. DESIGN: We implanted adult female Sprague-Dawley rats (N = 6) with electrodes to measure EEG, EKG, and EMG. Intermittent auditory stimuli (6-12 s) varying from 50 to 75 dBa were delivered over a 24-h period. Data were parsed into 2-s epochs and scored for wake/sleep state. RESULTS: All AEP components increased in amplitude with increased stimulus intensity during wake. During quiet sleep, however, only the early latency response (ELR) showed this relationship, while the middle latency response (MLR) increased at the highest 75 dBa intensity, and the late latency response (LLR) showed no significant change across the stimulus intensities tested. During rapid eye movement sleep (REM), both ELR and LLR increased, similar to wake, but MLR was severely attenuated. CONCLUSIONS: Stimulation intensity and the corresponding AEP response profile were dependent on both brain structure and sleep state. Lower brain structures maintained stimulus intensity and neural response relationships during sleep. This relationship was not observed in the cortex, implying state-dependent modification of stimulus intensity coding. Since AEP amplitude is not modulated by stimulus intensity during sleep, differences between paired 75/50 dBa stimuli could be used to determine state better than individual intensities. PMID- 22043125 TI - Antagonizing corticotropin-releasing factor in the central nucleus of the amygdala attenuates fear-induced reductions in sleep but not freezing. AB - STUDY OBJECTIVES: Contextual fear is followed by significant reductions in rapid eye movement sleep (REM) that are regulated by the central nucleus of the amygdala (CNA). Corticotropin-releasing factor (CRF) plays a major role in regulating the stress response as well as arousal, and CRF in CNA is implicated in stress-related behavior. To test the hypothesis that CRF regulation of CNA is involved in fear-induced alterations in REM, we determined the effects of microinjections into CNA of the CRF1 antagonist, antalarmin (ANT) on fear-induced reductions in REM. We also evaluated c-Fos activation in the hypothalamic paraventricular nucleus (PVN), locus coeruleus (LC), and dorsal raphe nucleus (DRN) to determine whether activation of these regions was consistent with their roles in regulating stress and in the control of REM. DESIGN: On separate days, rats were subjected to baseline and 2 shock training sessions (S1 and S2). Five days later, the rats received bilateral microinjections of ANT (4.8 mM) or vehicle (VEH) prior to exposure to the fearful context. Sleep was recorded for 20 h in each condition. Freezing was assessed during S1, S2, and context. Separate groups of rats received identical training and microinjections or handling control (HC) only, but were sacrificed 2 h after context exposure to assess c-Fos expression. SETTING: NA. PATIENTS OR PARTICIPANTS: NA. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Compared to baseline, S1 and S2 significantly reduced REM. Exposure to the fearful context reduced REM in VEH treated rats, whereas REM in ANT treated rats did not differ from baseline. ANT did not significantly alter freezing. Fear-induced c-Fos expression was decreased in PVN and LC after ANT compared to VEH. CONCLUSIONS: The results demonstrate that CRF receptors in CNA are involved in fear-induced reductions in REM and neural activation (as indicated by c-Fos) in stress and REM regulatory regions, but not in fear-induced freezing. PMID- 22043126 TI - Sleep-stage dynamics in patients with chronic fatigue syndrome with or without fibromyalgia. AB - STUDY OBJECTIVES: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are medically unexplained conditions that often have overlapping symptoms, including sleep-related complaints. However, differences between the 2 conditions have been reported, and we hypothesized that dynamic aspects of sleep would be different in the 2 groups of patients. PARTICIPANTS: Subjects were 26 healthy control subjects, 14 patients with CFS but without FM (CFS alone), and 12 patients with CFS and FM (CFS+FM)-all women. MEASUREMENTS AND RESULTS: We studied transition probabilities and rates between sleep stages (waking, rapid eye movement [REM] sleep, stage 1 [S1], stage 2 [S2], and slow-wave sleep [SWS]) and duration distributions of each sleep stage. We found that the probability of transition from REM sleep to waking was significantly greater in subjects with CFS alone than in control subjects, which may be the specific sleep problem for people with CFS alone. Probabilities of (a) transitions from waking, REM sleep, and S1 to S2 and (b) those from SWS to waking and S1 were significantly greater in subjects with CFS+FM than in control subjects; in addition, rates of these transitions were also significantly increased in subjects with CFS+FM. Result (a) might indicate increased sleep pressure in subjects with CFS+FM whereas result (b) may be the specific sleep problem of subjects with CFS+FM. We also found that shorter durations of S2 sleep are specific to patients with CFS+FM, not to CFS alone. CONCLUSIONS: These results suggest that CFS and FM may be different illnesses associated with different problems of sleep regulation. PMID- 22043127 TI - Evaluation of the association of menopausal status with delta and beta EEG activity during sleep. AB - STUDY OBJECTIVES: Women report increasing sleep difficulties during menopause, but polysomnographic measures do not detect sleep disturbances. We examined whether two spectral analysis sleep measures, delta and beta power, were related to menopausal status. DESIGN: The Study of Women's Health Across the Nation (SWAN) Sleep Study compared cross-sectionally spectral sleep measures in women in different stages of menopause. SETTING: Sleep EEG was recorded in the participants' homes with ambulatory recorders. PARTICIPANTS: A multi-ethnic cohort of premenopausal and early perimenopausal (n = 189), late perimenopausal (n = 73), and postmenopausal (n = 59) women. MEASUREMENTS: EEG power in the delta and beta frequency bands was calculated for all night NREM and all night REM sleep. Physical, medical, psychological, and socioeconomic data were collected from questionnaires and diaries. RESULTS: Beta EEG power in NREM and REM sleep in late perimenopausal and postmenopausal women exceeded that in pre- and early perimenopausal women. Neither all night delta power nor the trend in delta power across the night differed by menopausal status. In a multivariate model that controlled for the physical, demographic, behavioral, psychological, and health related changes that accompany menopause, beta power in both NREM and REM sleep EEG was significantly related to menopausal status. The frequency of hot flashes explained part but not all of the relation of beta power to menopausal status. CONCLUSIONS: Elevated beta EEG power in late perimenopausal and postmenopausal women provides an objective measure of disturbed sleep quality in these women. Elevated beta EEG activity suggests that arousal level during sleep is higher in these women. PMID- 22043129 TI - Self-reported sleep duration and time in bed as predictors of physical function decline: results from the InCHIANTI study. AB - STUDY OBJECTIVES: To characterize elderly persons into sleep/rest groups based on their self-reported habitual total sleeping time (TST) and habitual time in bed (TIB) and to examine the prospective association between sleep/rest behavior on physical function decline. DESIGN: Population-based InCHIANTI study with 6 years follow-up (Tuscany, Italy). SETTING: Community. PARTICIPANTS: Men and women aged >= 65 years (n = 751). MEASUREMENTS AND RESULTS: At baseline, participants were categorized into 5 sleep/rest behavior groups according to their self-reported TST and TIB, computed from bedtime and wake-up time. Physical function was assessed at baseline and at 3- and 6-year follow-ups as walking speed, the Short Physical Performance Battery (SPPB), and self-reported mobility disability (ability to walk 400 m or climb one flight of stairs). Both long (>= 9 h) TST and long TIB predicted accelerated decline in objectively measured physical performance and greater incidence in subjectively assessed mobility disability, but short (<= 6 h) TST did not. After combining TST and TIB, long sleepers (TST and TIB >= 9 h) experienced the greatest decline in physical performance and had the highest risk for incident mobility disability in comparison to mid-range sleepers with 7-8 h TST and TIB. Subjective short sleepers reporting short (<= 6 h) TST but long (>= 9 h) TIB showed a greater decline in SPPB score and had a higher risk of incident mobility disability than true short sleepers with short (<= 6 h) TST and TIB <= 8 hours. CONCLUSIONS: Extended time in bed as well as long total sleeping time is associated with greater physical function decline than mid-range or short sleep. TIB offers important additive information to the self-reported sleep duration when evaluating the consequences of sleep duration on health and functional status. PMID- 22043128 TI - Quantification of the fragmentation of rest-activity patterns in elderly individuals using a state transition analysis. AB - OBJECTIVES: Recent interest in the temporal dynamics of behavioral states has spurred the development of analytical approaches for their quantification. Several analytical approaches for polysomnographic data have been described. However, polysomnography is cumbersome, perturbs behavior, and is limited to short recordings. Although less physiologically comprehensive than polysomnography, actigraphy is nonintrusive, amenable to long recordings, and suited to use in subjects' natural environments, and provides an indirect measure of behavioral state. We developed a probabilistic state transition model to quantify the fragmentation of human rest-activity patterns from actigraphic data. We then applied this to the study of the temporal dynamics of rest-activity patterns in older individuals. DESIGN: Cross-sectional. SETTING: Community-based. PARTICIPANTS: 621 community-dwelling individuals without dementia participating in the Rush Memory and Aging Project. MEASUREMENTS AND RESULTS: We analyzed actigraphic data collected for up to 11 days. We processed each record to give a series of transitions between the states of rest and activity, calculated the probabilities of such transitions, and described their evolution as a function of time. From these analyses, we derived metrics of the fragmentation of rest or activity at scales of seconds to minutes. Regression modeling of the relationship of these metrics with clinical variables revealed significant associations with age, even after adjusting for sex, body mass index, and a broad range of medical comorbidities. CONCLUSIONS: Probabilistic analyses of the transition dynamics of rest-activity data provide a high-throughput, automated, quantitative, and noninvasive method of assessing the fragmentation of behavioral states suitable for large scale human and animal studies; these methods reveal age-associated changes in the fragmentation of rest-activity patterns akin to those described using polysomnographic methods. PMID- 22043130 TI - Ethnic disparities in CPAP adherence in New Zealand: effects of socioeconomic status, health literacy and self-efficacy. AB - STUDY OBJECTIVES: We aimed to investigate the influence of ethnicity on adherence with continuous positive airway pressure (CPAP) in a sample of New Zealand patients. DESIGN: Observational study over one month. SETTING: A university-based sleep laboratory. PATIENTS: 126 consecutively consenting CPAP-naive patients (19.8% Maori, mean+/-SD apnea-hypopnea index 57.9 +/- 38.9 events/h, CPAP 11.1 +/ 3.1 cm H2O). INTERVENTIONS: Patients underwent a 4-week supervised home trial of CPAP following pressure titration. MEASUREMENTS AND RESULTS: Self-identified ethnicity (Maori/non-Maori), Epworth Sleepiness Scale, Self-Efficacy Measure for Sleep Apnea, Rapid Estimate of Adult Literacy in Medicine, New Zealand Deprivation Index (calculated from residential address), New Zealand Individual Deprivation Index (validated 8-item questionnaire), educational history, income, and employment assessed at baseline were compared to objective CPAP adherence after one month. Maori demonstrated significantly lower usage than non-Maori (median 5.11, interquartile range 2.24 h/night compared with median 5.71, interquartile range 2.61 h/night, P = 0.05). There were no significant relationships between adherence and subjective sleepiness, health literacy, or self-efficacy. In a multivariate logistic regression model incorporating 5 variables (ethnicity, eligibility for government-subsidized healthcare, individual deprivation scores, income, and education), non-completion of tertiary education, and high individual socioeconomic deprivation remained significant independent predictors of average CPAP adherence not reaching >= 4 h (odds ratio 0.25, 95% CI 0.08-0.83, P = 0.02; odds ratio 0.10, 95% CI 0.02-0.86, P = 0.04, respectively). The overall model explained approximately 23% of the variance in adherence. CONCLUSIONS: The disparity in CPAP adherence demonstrated between Maori and non-Maori can be explained in part by lower education levels and socioeconomic status. PMID- 22043131 TI - Increased aortic root size is associated with nocturnal hypoxia and diastolic blood pressure in obstructive sleep apnea. AB - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is known as a major cardiovascular risk factor, and high prevalence of OSA has been reported in patients with thoracic aortic dissection. The aim of our study was to assess the relationship between OSA, its vascular consequences, and aortic root size. DESIGN/PATIENTS: 156 newly diagnosed apneic patients free of cardiovascular disease and medication were included. Patients underwent cardiac ultrasound for measuring aortic root diameter, polysomnography, office and 24-h ambulatory blood pressure (BP) measurements, baroreflex sensitivity (BRS), and arterial stiffness evaluation by carotid-to-femoral pulse wave velocity (PWV). MEASUREMENTS AND RESULTS: In univariate analysis, greater aortic root size was associated with older age (P = 0.03) and severity of OSA as expressed by mean nocturnal oxygen saturation (SpO2) (P = 0.015). Moreover, greater aortic root size was associated with higher diastolic BP, measured both clinically (P = 0.0005) or by 24-h ambulatory BP monitoring (P = 0.02), and PWV (P = 0.03). Mean nocturnal SpO(2) was correlated with BRS (P = 0.0008), thus potentially influencing BP values and arterial stiffness. In multivariate stepwise regression analysis, diastolic BP was the only significant factor for aortic root size (P = 0.0003). CONCLUSIONS: In OSA patients, nocturnal hypoxemia decreased BRS and increased diastolic BP, which was the main factor influencing aortic root size. PMID- 22043133 TI - VALUES AND LIMITATIONS OF STATISTICAL MODELS. AB - Methodological consequences of population heterogeneity for the sequential logit model in studies of education transitions are now well understood. There are two main mechanisms by which heterogeneity may cause biases to parameter estimates in sequential logit models: outcome incommensurability and population incommensurability. These methodological problems are intrinsic to the substantive research question and thus are not easily remediable with better statistical models. All statistical solutions require extra information in the form of additional data or additional assumptions. In some settings, the researcher may explicitly introduce a form of heterogeneity into the sequential logit model and then evaluate the model. In other settings, the researcher may wish to stay with the conventional sequential logit model and interpret the results descriptively. PMID- 22043134 TI - Tracking Passive Sentence Comprehension in Agrammatic Aphasia. AB - People with agrammatic aphasia often experience greater difficulty comprehending passive compared to active sentences. The Trace Deletion Hypothesis (TDH; Grodzinsky, 2000) proposes that aphasic individuals cannot generate accurate syntactic representations of passive sentences and, hence, use an agent-first processing strategy which leads to at-chance performance. We tested this claim using the eyetracking-while-listening paradigm in order to reveal online processing routines. Ten agrammatic aphasic participants and 10 age-matched controls listened to passive and active sentences and performed a sentence picture matching task (i.e., selecting between two pictures with reversed thematic roles), while their eye movements were monitored. Control participants' performance was at ceiling, whereas accuracy for the aphasic participants was above chance for active sentences and at chance for passive sentences. Further, for the control participants, the eye movement data showed an initial agent-first processing bias, followed by fixation on the correct picture in the vicinity of the verb in both active and passive sentences. However, the aphasic participants showed no evidence of agent-first processing, counter the predictions of the TDH. In addition, in active sentences, they reliably fixated the correct picture only at sentence offset, reflecting slowed processing. During passive sentence processing, fixations were at chance throughout the sentence, but different patterns were noted for correct and incorrect trials. These results are consistent with the proposal that agrammatic sentence comprehension failure involves lexical processing and/or lexical integration deficits. PMID- 22043135 TI - Study yourself too. PMID- 22043136 TI - Baby boy blue - why is this newborn lethargic? PMID- 22043137 TI - The need for public involvement when operating a regionalized neonatal care system at maximum capacity. PMID- 22043138 TI - Case 1: A not-so-routine case of fever for five days. PMID- 22043139 TI - Case 2: Where have all the white cells gone? PMID- 22043140 TI - Deformity of the tongue in an infant: Riga-Fede disease. AB - Riga-Fede is the rare condition of benign ulceration caused by repetitive trauma to the lingual tissues by the teeth in children younger than two years of age. The differential diagnosis includes infective and neoplastic conditions. Histological diagnosis is required when the symptoms fail to resolve with standard management. The case involving an 11-month-old girl who presented with ulceration of the tongue, resulting in a reasonable defect of the tongue tip, is reported in the present article. Following excisional biopsy, the lesion healed without subsequent recurrence. Riga-Fede disease should be considered in infants presenting with oral ulceration. Extraction of the offending teeth should be considered when associated with failure to thrive or failed conservative management. PMID- 22043141 TI - Development of an integrated child health information system for children who are deaf or hard of hearing. AB - Young children who are deaf or hard of hearing typically participate in health and early intervention service structures involving multiple agencies and service providers, all of whom may be responsive to a child's and family's needs, but remain mutually distinct with minimal interdependence. Lack of coordination may result in fragmented service delivery and may be counterproductive to the provision of family centred services. Increasingly, advancements in technology, such as the development of integrated child health information systems, have facilitated greater coordination and integration of service delivery in multidisciplinary and multisite program contexts. In the present article, the process of developing an integrated child health information system for a new provincial early hearing detection and intervention program in British Columbia is described. Key considerations for system development included the following: the nature of the preprogram structure for information management and sharing; the need for modifications of the structure; and ways that the structure could be improved. PMID- 22043142 TI - Newborn screening for cystic fibrosis in Alberta: Two years of experience. AB - On April 1, 2007, Alberta became the first province in Canada to introduce cystic fibrosis (CF) to its newborn screening program. The Alberta protocol involves a two-tier algorithm involving an immunoreactive trypsinogen measurement followed by molecular analysis using a CF panel for 39 mutations. Positive screens are followed up with sweat chloride testing and an assessment by a CF specialist. Of the 99,408 newborns screened in Alberta during the first two years of the program, 221 had a positive CF newborn screen. The program subsequently identified and initiated treatment in 31 newborns with CF. A relatively high frequency of the R117H mutation and the M1101K mutation was noted. The M1101K mutation is common in the Hutterite population. The presence of the R117H mutation has created both counselling and management dilemmas. The ability to offer CF transmembrane regulator full sequencing may help resolve diagnostic dilemmas. Counselling and management challenges are created when mutations are mild or of unknown clinical significance. PMID- 22043143 TI - Human milk banking. AB - It is universally accepted that breast milk is the optimum exclusive source of nutrition for the first six months of life, and may remain part of the healthy infant diet for the first two years of life and beyond. Despite advances in infant formulas, human breast milk provides a bioactive matrix of benefits that cannot be replicated by any other source of nutrition. When the mother's own milk is unavailable for the sick, hospitalized newborn, pasteurized human donor breast milk should be made available as an alternative feeding choice followed by commercial formula. There is a limited supply of donor breast milk in Canada and it should be prioritized to sick, hospitalized neonates who are the most vulnerable and most likely to benefit from exclusive human milk feeding. PMID- 22043144 TI - Antifungal agents for the treatment of systemic fungal infections in children. AB - Traditionally, the mainstay of systemic antifungal therapy has been amphotericin B deoxycholate (conventional amphotericin B). Newer agents have been developed to fulfill special niches and to compete with conventional amphotericin B by virtue of having more favourable toxicity profiles. Some agents have displaced conventional amphotericin B for the treatment of specific fungal diseases. For example, voriconazole has emerged as the preferred treatment for invasive pulmonary aspergillosis. This notwithstanding, conventional amphotericin B remains a useful agent for the treatment of paediatric fungal infections. Knowledge of the characteristics of the newer agents is important, given the increasing numbers of patients who are being treated with these drugs. Efforts need to be directed at research aimed at generating paediatric data where these are lacking. The antifungal agents herein described are most often used as monotherapy regimens because there is no uniform consensus on the value of combination therapy, except for specific scenarios. PMID- 22043145 TI - Using path analysis to understand parents' perceptions of their children's weight, physical activity and eating habits in the Champlain region of Ontario. AB - INTRODUCTION: Parents have a fundamental role in promoting the healthy weight of their children. OBJECTIVES: To determine parental perceptions of their child's body weight, eating and physical activity (PA) behaviours, and to test a predictive model of parental perceptions regarding their child's PA and healthy eating behaviours. METHODS: A random-digit telephone survey was conducted among parents of children four to 12 years of age living in the Champlain region of Ontario. Descriptive statistics were used to summarize the responses. Path analysis was used to identify predictors of parental perceptions of PA and healthy eating. RESULTS: The study sample consisted of 1940 parents/caregivers. Only 0.2% of parents reported their child as being obese; 8.6% reported their child as being overweight. Most parents perceived their child to be physically active and eating healthily. Approximately 25% of parents reported that their child spent 2 h/day or more in front of a screen, and that their child consumed less than three servings of fruits and vegetables daily, and regularly consumed fast food. Variables that correlated with PA perceptions included time spent reading/doing homework, interest in PA, perceived importance of PA, frequency of PA, level of parental PA, participation in organized sport, child weight and parental concern for weight. Variables that predicted perceptions regarding healthy eating were parental education, household income, preparation of home cooked meals, fruit and vegetable intake, and concern for and influence on the child's weight. CONCLUSIONS: Parents in the present study sample did not appear to understand, or had little knowledge of the recommendations for PA and healthy eating in children. Parents appeared to base their judgment of healthy levels of PA or healthy eating behaviours using minimal criteria; these criteria are inconsistent with those used by health professionals to define adequate PA and healthy eating. The present survey highlights an important knowledge gap between scientific opinion and parental perceptions of the criteria for healthy PA and eating behaviours. PMID- 22043146 TI - Diffusion tensor imaging: exploring the motor networks and clinical applications. AB - With the advances in diffusion magnetic resonance (MR) imaging techniques, diffusion tensor imaging (DTI) has been applied to a number of neurological conditions because DTI can demonstrate microstructures of the brain that are not assessable with conventional MR imaging. Tractography based on DTI offers gross visualization of the white matter fiber architecture in the human brain in vivo. Degradation of restrictive barriers and disruption of the cytoarchitecture result in changes in the diffusion of water molecules in various pathological conditions, and these conditions can also be assessed with DTI. Yet many factors may influence the ability to apply DTI clinically, so these techniques have to be used with a cautious hand. PMID- 22043147 TI - Time-resolved 3D contrast-enhanced MRA on 3.0T: a non-invasive follow-up technique after stent-assisted coil embolization of the intracranial aneurysm. AB - OBJECTIVE: To evaluate the usefulness of time-resolved contrast enhanced magnetic resonance angiography (4D MRA) after stent-assisted coil embolization by comparing it with time of flight (TOF)-MRA. MATERIALS AND METHODS: TOF-MRA and 4D MRA were obtained by 3T MRI in 26 patients treated with stent-assisted coil embolization (Enterprise:Neuroform = 7:19). The qualities of the MRA were rated on a graded scale of 0 to 4. We classified completeness of endovascular treatment into three categories. The degree of quality of visualization of the stented artery was compared between TOF and 4D MRA by the Wilcoxon signed rank test. We used the Mann-Whitney U test for comparing the quality of the visualization of the stented artery according to the stent type in each MRA method. RESULTS: The quality in terms of the visualization of the stented arteries in 4D MRA was significantly superior to that in 3D TOF-MRA, regardless of type of the stent (p < 0.001). The quality of the arteries which were stented with Neuroform was superior to that of the arteries stented with Enterprise in 3D TOF (p < 0.001) and 4D MRA (p = 0.008), respectively. CONCLUSION: 4D MRA provides a higher quality view of the stented parent arteries when compared with TOF. PMID- 22043148 TI - Lymphomatoid granulomatosis: CT and FDG-PET findings. AB - OBJECTIVE: Lymphomatoid granulomatosis (LG) is a rare, aggressive extranodal Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disease. The purpose of our study was to analyze the CT and fluorodeoxyglucose positron emission tomography (FDG-PET) findings of pulmonary LG. MATERIALS AND METHODS: Between 2000 and 2009, four patients with pathologically proven pulmonary LG and chest CT were identified. Two of these patients also had FDG-PET. Imaging features of LG on CT and PET were reviewed. RESULTS: Pulmonary nodules or masses with peribronchovascular, subpleural, and lower lung zonal preponderance were present in all patients. Central low attenuation (4 of 4 patients), ground-glass halo (3 of 4 patients), and peripheral enhancement (4 of 4 patients) were observed in these nodules and masses. An air-bronchogram and cavitation were seen in three of four patients. FDG-PET scans demonstrated avid FDG uptake in the pulmonary nodules and masses. CONCLUSION: Pulmonary LG presents with nodules and masses with a lymphatic distribution, as would be expected for a lymphoproliferative disease. However, central low attenuation, ground-glass halo and peripheral enhancement of the nodules/masses are likely related to the angioinvasive nature of this disease. Peripheral enhancement and ground-glass halo, in particular, are valuable characteristic not previously reported that can help radiologists suggest the diagnosis of pulmonary LG. PMID- 22043149 TI - 3D whole-heart coronary MR angiography at 1.5T in healthy volunteers: comparison between unenhanced SSFP and Gd-enhanced FLASH sequences. AB - OBJECTIVE: To validate the optimal cardiac phase and appropriate acquisition window for three-dimensional (3D) whole-heart coronary magnetic resonance angiography (MRA) with a steady-state free precession (SSFP) sequence, and to compare image quality between SSFP and Gd-enhanced fast low-angle shot (FLASH) MR techniques at 1.5 Tesla (T). MATERIALS AND METHODS: Thirty healthy volunteers (M:F = 25:5; mean age, 35 years; range, 24-54 years) underwent a coronary MRA at 1.5T. 3D whole-heart coronary MRA with an SSFP was performed at three different times: 1) at end-systole with a narrow (120-msec) acquisition window (ESN), 2) mid-diastole with narrow acquisition (MDN); and 3) mid-diastole with wide (170 msec) acquisition (MDW). All volunteers underwent a contrast enhanced coronary MRA after undergoing an unenhanced 3D true fast imaging with steady-state precession (FISP) MRA three times. A contrast enhanced coronary MRA with FLASH was performed during MDN. Visibility of the coronary artery and image quality were evaluated for 11 segments, as suggested by the American Heart Association. Image quality was scored by a five-point scale (1 = not visible to 5 = excellent). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were evaluated at the proximal coronary arteries. RESULTS: The SSFP sequence rendered higher visibility coronary segments, higher image quality, as well as higher SNR and CNR than the Gd-enhanced FLASH technique at 1.5T (p < 0.05). The visibility of coronary segments, image quality, SNR and CNR in the ESN, MDN and MDW with SSFP sequence did not differ significantly. CONCLUSION: An SSFP sequence provides an excellent method for the 3D whole-heart coronary MRA at 1.5T. Contrast enhanced coronary MRA using the FLASH sequence does not help improve the visibility of coronary segments, image quality, SNR or CNR on the 3D whole-heart coronary MRA. PMID- 22043150 TI - Isolated noncompaction of ventricular myocardium: a magnetic resonance imaging study of 11 patients. AB - OBJECTIVE: To retrospectively summarize the cardiac magnetic resonance imaging (CMRI) findings of isolated noncompaction of ventricular myocardium (INVM). MATERIALS AND METHODS: Eleven patients (M:F = 9:2; mean age, 35 years) were evaluated. Steady-state free precession (SSFP), fast spin echo (SE) sequence, SSFP cine imaging, and delayed enhanced inversion recovery spoiled gradient echo (IR-SPGR) sequence were used for showing abnormal myocardium, measuring ratio of noncompacted/compacted myocardium layers (NC/C ratio), and detecting myocardial viability. The left ventricle was divided into nine segments and a NC/C ratio > 2.3 in diastole was used as cutoff value in diagnosing left INVM. The right ventricle was assessed qualitatively. RESULTS: Cardiac MRI indicated left INVM in seven patients, right INVM in one patient and biventricle INVM in three patients. Characteristic CMRI changes included prominent trabeculations, deep intertrabecular recesses and an increase in the NC/C ratio. The most frequently involved segments was left ventricular apex. Three patients had abnormal high signals within the trabecular structures on SE T2 weighted image. One ventricular aneurysm and one apical thrombus were also observed. Delayed enhancement was seen in six of nine patients with subendocardial and transmural patterns. CONCLUSION: There are CMRI features that might be characteristic for INVM. PMID- 22043151 TI - Hepatocellular carcinomas smaller than 4 cm supplied by the intercostal artery: can we predict which intercostal artery supplies the tumor? AB - OBJECTIVE: To predict which intercostal artery supplies a tumor by examining the spatial relationship between hepatocellular carcinoma (HCC) and the intercostal artery feeding the tumor on transverse computed tomography (CT) images. MATERIALS AND METHODS: Between January 2000 and September 2009, 46 intercostal arteries supplying HCCs smaller than 4 cm were noted in 44 patients, and CT scans and angiograms of these patients were retrospectively reviewed. The intercostal artery feeding the tumor was marked on the CT scan showing the center of the tumor. In addition, its spatial relationship with the tumor center was examined. The angle of the tumor location was measured on the transverse CT scan in the clockwise direction from the sagittal line on the virtual circle centered in the right hemithorax. Correlations between the angle of the tumor location and the level of the tumor-feeding intercostal artery were assessed with the Spearman rank coefficient. RESULTS: Of 46 intercostal arteries feeding HCC, 39 (85%) were the first ones observed from the tumor center in a counterclockwise direction on the transverse CT image containing the tumor center. The level of the tumor feeding intercostal artery was significantly correlated with the angle of the tumor, as the posteriorly located tumor tends to be supplied by lower intercostal arteries, while the laterally located tumor by upper intercostal arteries (Spearman coefficient = -0.537; p < 0.001). CONCLUSION: We can predict the tumor feeder with an accuracy of 85% as the first intercostal artery encountered from the tumor center in a counterclockwise direction on a transverse CT image. PMID- 22043152 TI - CT analysis of retropharyngeal abnormality in Kawasaki disease. AB - OBJECTIVE: To retrospectively compare the imaging characteristics of retropharyngeal density and associated findings for Kawasaki disease with those for non-Kawasaki disease, and identify the distinguishing features which aid the CT diagnosis of Kawasaki disease with retropharyngeal low density. MATERIALS AND METHODS: Among the enhanced neck CT performed in children less than 8-years old with clinical presentation of fever and cervical lymphadenopathy over a 6-year period, only cases with retropharyngeal low density (RLD) were included in this study. The 56 cases of RLD were divided into two groups; group A included cases diagnosed as Kawasaki disease (n = 34) and group B included cases diagnosed as non-Kawasaki disease (n = 22). We evaluated the CT features including the thickness of RLD and its extent into the deep neck spaces, as well as soft tissue change in the adjacent structure. We also scored the extent of RLD into the deep neck spaces and the soft tissue changes in the adjacent structure. RESULTS: The thickness of RLD was greater in group A than in group B (group A, 6.0 +/- 2.1; group B, 4.6 +/- 1.5, p = 0.01). The score of the RLD extent into the deep neck spaces was significantly greater in group A than in group B (group A, 2.3 +/- 1.3; group B, 0.8 +/- 1.0, p < 0.01). Also, the score of the adjacent soft tissue changes was greater in group A than in group B (group A, 2.0 +/- 1.1; group B, 1.0 +/- 1.0, p < 0.01). CONCLUSION: If children present with fever and cervical lymphadenopathy that display retropharyngeal low density with extension into more deep neck spaces as well as changes in more adjacent soft tissue, the possibility of Kawasaki disease should be considered. PMID- 22043153 TI - Temporary placement of stent grafts in postsurgical benign biliary strictures: a single center experience. AB - OBJECTIVE: To evaluate the effect of temporary stent graft placement in the treatment of benign anastomotic biliary strictures. MATERIALS AND METHODS: Nine patients, five women and four men, 22-64 years old (mean, 47.5 years), with chronic benign biliary anastomotic strictures, refractory to repeated balloon dilations, were treated by prolonged, temporary placement of stent-grafts. Four patients had strictures following a liver transplantation; three of them in bilio enteric anastomoses and one in a choledocho-choledochostomy. Four of the other five patients had strictures at bilio-enteric anastomoses, which developed after complications following laparoscopic cholecystectomies and in one after a Whipple procedure for duodenal carcinoma. In eight patients, balloon-expandable stent grafts were placed and one patient was treated by insertion of a self-expanding stent-graft. RESULTS: In the transplant group, treatment of patients with bilio enteric anastomoses was unsuccessful (mean stent duration, 30 days). The patient treated for stenosis in the choledocho-choledochostomy responded well to consecutive self-expanding stent-graft placement (total placement duration, 112 days). All patients with bilio-enteric anastomoses in the non-transplant group were treated successfully with stent-grafts (mean placement duration, 37 days). CONCLUSION: Treatment of benign biliary strictures with temporary placement of stent-grafts has a positive effect, but is less successful in patients with strictures developed following a liver transplant. PMID- 22043154 TI - A comparison of the use of contrast media with different iodine concentrations for multidetector CT of the kidney. AB - OBJECTIVE: To determine the optimal iodine concentration of contrast media for kidney multidetector computed tomography (MDCT) by comparing the degree of renal parenchymal enhancement and the severity of the renal streak artifact with contrast media of different iodine concentrations. MATERIALS AND METHODS: A 16 row MDCT was performed in 15 sedated rabbits by injection of 2 mL contrast media/kg body weight at a rate of 0.3 mL/sec. Monomeric nonionic contrast media of 250, 300, and 370 mg iodine/mL were injected at 1-week intervals. Mean attenuation values were measured in each renal structure with attenuation differences among the structures. The artifact was evaluated by CT window width/level and three grading methods. The values were compared with iodine concentrations. RESULTS: The 370 mg iodine/mL concentration showed significantly higher cortical enhancement than 250 mg iodine/mL in all phases (p < 0.05). There was however no significant difference in the degree of enhancement between the 300 mg iodine/mL and 370 mg iodine/mL concentrations in all phases. There is a significant difference in attenuation for the cortex-outer medulla between 250 mg iodine/mL and 300 mg iodine/mL (p < 0.05). The artifact was more severe with a medium of 370 mg iodine/mL than with 250 mg iodine/mL by all grading methods (p < 0.05). CONCLUSION: The 300 mg iodine/mL is considered to be the most appropriate iodine concentration in an aspect of the enhancement and artifact on a kidney MDCT scan. PMID- 22043155 TI - Correlations of 3T DCE-MRI quantitative parameters with microvessel density in a human-colorectal-cancer xenograft mouse model. AB - OBJECTIVE: To investigate the correlation between quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters and microvascular density (MVD) in a human-colon-cancer xenograft mouse model using 3 Tesla MRI. MATERIALS AND METHODS: A human-colon-cancer xenograft model was produced by subcutaneously inoculating 1 * 10(6) DLD-1 human-colon-cancer cells into the right hind limbs of 10 mice. The tumors were allowed to grow for two weeks and then assessed using MRI. DCE-MRI was performed by tail vein injection of 0.3 mmol/kg of gadolinium. A region of interest (ROI) was drawn at the midpoints along the z-axes of the tumors, and a Tofts model analysis was performed. The quantitative parameters (K(trans), K(ep) and V(e)) from the whole transverse ROI and the hotspot ROI of the tumor were calculated. Immunohistochemical microvessel staining was performed and analyzed according to Weidner's criteria at the corresponding MRI sections. Additional Hematoxylin and Eosin staining was performed to evaluate tumor necrosis. The Mann-Whitney test and Spearman's rho correlation analysis were performed to prove the existence of a correlation between the quantitative parameters, necrosis, and MVD. RESULTS: Whole transverse ROI of the tumor showed no significant relationship between the MVD values and quantitative DCE-MRI parameters. In the hotspot ROI, there was a difference in MVD between low and high group of K(trans) and K(ep) that had marginally statistical significance (ps = 0.06 and 0.07, respectively). Also, K(trans) and K(ep) were found to have an inverse relationship with MVD (r = -0.61, p = 0.06 in K(trans); r = -0.60, p = 0.07 in K(ep)). CONCLUSION: Quantitative analysis of T1 weighted DCE-MRI using hotspot ROI may provide a better histologic match than whole transverse section ROI. Within the hotspots, K(trans) and K(ep) tend to have a reverse correlation with MVD in this colon cancer mouse model. PMID- 22043156 TI - Pancreatic tumors: emphasis on CT findings and pathologic classification. AB - Pancreatic tumors can be classified by their morphologic features on CT. The subtypes include solid tumors, mixed cystic and solid lesions, unilocular cysts, multilocular cystic lesions, and microcystic lesions. Endoscopic US and MRI can provide detailed information for classifying pancreatic lesions. Each subtype has different kinds of tumors and malignant potential, thus the classification can be useful for a better differential diagnosis and treatment planning. For this purpose, we suggest an appropriate modified classification system by using the imaging features of pancreatic tumors with an emphasis on CT findings and illustrate various findings of typical and atypical manifestations. PMID- 22043157 TI - Bilateral carotid and vertebral rete mirabile presenting with a prominent anterior spinal artery mimicking a spinal dural AV fistula at MRI. AB - Bilateral carotid and vertebral rete mirabile (CVRM) is a very rare condition. We report a new case of CVRM initially detected by magnetic resonance imaging (MRI) of the cervical spine. MRI demonstrated tortuous vascular signal voids limited to the anterior cerebrospinal fluid space mimicking spinal dural arteriovenous fistula. A diagnosis of CVRM was confirmed on the basis of angiographic findings of rete formation associated with bilateral aplasia of the cavernous internal carotid and vertebral arteries without abnormal arteriovenous connection. PMID- 22043158 TI - Nontuberculous mycobacterial tenosynovitis in the hand: two case reports with the MR imaging findings. AB - Nontuberculous mycobacterial infections can cause destructive tenosynovitis of the hand. We report on and discuss the clinical course and distinctive radiologic findings of two patients with hand tenosynovitis secondary to M. marinum and intracellulare infection, which are different from those of the nontuberculous mycobacterial infections reported in the previous literature. PMID- 22043159 TI - Malignant mesothelioma presenting as a giant chest, abdominal and pelvic wall mass. AB - Malignant mesothelioma (MM) is a relatively rare carcinoma of the mesothelial cells, and it is usually located in the pleural or peritoneal cavity. Here we report on a unique case of MM that developed in the chest, abdominal and pelvic walls in a 77-year-old female patient. CT and MRI revealed mesothelioma that manifested as a giant mass in the right flank and bilateral pelvic walls. The diagnosis was confirmed by the pathology and immunohistochemistry. Though rare, accurate investigation of the radiological features of a body wall MM may help make an exact diagnosis. PMID- 22043160 TI - Evaluating a thrombosed azygous vein aneurysm combined with pulmonary arterial thromboembolism by ECG-gated multidetector CT: a case report. AB - Azygous vein aneurysm is a rare congenital lesion that needs to be differentiated from mediastinal mass lesions. Although almost of these anomalies are asymptomatic lesions, we experienced an interesting case in which a thrombus within an azygous vein aneurysm in a 75-year-old woman caused pulmonary thromboembolism. The patient was managed by medical treatment for one month and then the thrombus within both the azygous vein aneurysm and the pulmonary arteries completely resolved. PMID- 22043161 TI - Secondary omental infarction related to open and laparoscopic-assisted distal gastrectomy: report of two cases. AB - Omental infarction occurring after open and laparoscopic-assisted distal gastrectomy with partial omentectomy for gastric cancer was a very rare disease in the past, but its incidence has increased as more partial omentectomies are now being performed. But there are few case reports or radiologic studies on its increasing incidence. It is necessary to differentiate omental infarction from carcinomatosis peritonei, since both have similar imaging findings. In this report, we describe two cases of omental infarction; each occurred after open and laparoscopic-assisted distal gastrectomy in early gastric cancer patients. Partial omentectomy was performed in both cases. Omental infarction following distal gastrectomy with partial omentectomy can be discriminated from carcinomatosis peritonei by comparing with different initial and follow up CT findings. PMID- 22043163 TI - Genomics of childhood obesity. PMID- 22043162 TI - A rare case of epiphyseal chondromyxoid fibroma of the proximal tibia. AB - Chondromyxoid fibroma is an uncommon benign cartilaginous tumor of the bone. It occurs most frequently in the metaphysis of long tubular bones, and an epiphyseal location is exceedingly rare. We present here an unusual case of a chondromyxoid fibroma that occurred in the epiphysis of the proximal tibia with an open growth plate. MR imaging findings of this tumor, which has, to the best of our knowledge, never been described in an epiphyseal location, makes the present case unique. PMID- 22043164 TI - Molecular basis of obesity: current status and future prospects. AB - Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of "deep phenotyping" lead to optimism to chip away at the 'missing heritability' of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity. PMID- 22043165 TI - Genetics of Obesity: What have we Learned? AB - Candidate gene and genome-wide association studies have led to the discovery of nine loci involved in Mendelian forms of obesity and 58 loci contributing to polygenic obesity. These loci explain a small fraction of the heritability for obesity and many genes remain to be discovered. However, efforts in obesity gene identification greatly modified our understanding of this disorder. In this review, we propose an overlook of major lessons learned from 15 years of research in the field of genetics and obesity. We comment on the existence of the genetic continuum between monogenic and polygenic forms of obesity that pinpoints the role of genes involved in the central regulation of food intake and genetic predisposition to obesity. We explain how the identification of novel obesity predisposing genes has clarified unsuspected biological pathways involved in the control of energy balance that have helped to understand past human history and to explore causality in epidemiology. We provide evidence that obesity predisposing genes interact with the environment and influence the response to treatment relevant to disease prediction. PMID- 22043166 TI - Gene-diet interactions in childhood obesity. AB - Childhood overweight and obesity have reached epidemic proportions worldwide, and the increase in weight-associated co-morbidities including premature type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease will soon become major healthcare and economic problems. A number of studies now indicate that the childhood obesity epidemic which has emerged during the past 30 years is a complex multi-factorial disease resulting from interaction of susceptibility genes with an obesogenic environment. This review will focus on gene-diet interactions suspected of having a prominent role in promoting childhood obesity. In particular, the specific genes that will be presented (FTO, MC4R, and NPC1) have recently been associated with childhood obesity through a genome-wide association study (GWAS) and were shown to interact with nutritional components to increase weight gain. Although a fourth gene (APOA2) has not yet been associated with childhood obesity, this review will also present information on what now represents the best characterized gene-diet interaction in promoting weight gain. PMID- 22043167 TI - Structural Chromosome Abnormalities Associated with Obesity: Report of Four New subjects and Review of Literature. AB - Obesity in humans is a complex polygenic trait with high inter-individual heritability estimated at 40-70%. Candidate gene, DNA linkage and genome-wide association studies (GWAS) have allowed for the identification of a large set of genes and genomic regions associated with obesity. Structural chromosome abnormalities usually result in congenital anomalies, growth retardation and developmental delay. Occasionally, they are associated with hyperphagia and obesity rather than growth delay. We report four new individuals with structural chromosome abnormalities involving 10q22.3-23.2, 16p11.2 and Xq27.1-q28 chromosomal regions with early childhood obesity and developmental delay. We also searched and summarized the literature for structural chromosome abnormalities reported in association with childhood obesity. PMID- 22043168 TI - Prader-Willi Syndrome: Obesity due to Genomic Imprinting. AB - Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder due to errors in genomic imprinting with loss of imprinted genes that are paternally expressed from the chromosome 15q11-q13 region. Approximately 70% of individuals with PWS have a de novo deletion of the paternally derived 15q11-q13 region in which there are two subtypes (i.e., larger Type I or smaller Type II), maternal disomy 15 (both 15s from the mother) in about 25% of cases, and the remaining subjects have either defects in the imprinting center controlling the activity of imprinted genes or due to other chromosome 15 rearrangements. PWS is characterized by a particular facial appearance, infantile hypotonia, a poor suck and feeding difficulties, hypogonadism and hypogenitalism in both sexes, short stature and small hands and feet due to growth hormone deficiency, mild learning and behavioral problems (e.g., skin picking, temper tantrums) and hyperphagia leading to early childhood obesity. Obesity is a significant health problem, if uncontrolled. PWS is considered the most common known genetic cause of morbid obesity in children. The chromosome 15q11-q13 region contains approximately 100 genes and transcripts in which about 10 are imprinted and paternally expressed. This region can be divided into four groups: 1) a proximal non-imprinted region; 2) a PWS paternal-only expressed region containing protein-coding and non-coding genes; 3) an Angelman syndrome region containing maternally expressed genes and 4) a distal non-imprinted region. This review summarizes the current understanding of the genetic causes, the natural history and clinical presentation of individuals with PWS. PMID- 22043169 TI - Fragile x syndrome. AB - Recent data from a national survey highlighted a significant difference in obesity rates in young fragile X males (31%) compared to age matched controls (18%). Fragile X syndrome (FXS) is the most common cause of intellectual disability in males and the most common single gene cause of autism. This X linked disorder is caused by an expansion of a trinucleotide CGG repeat (>200) on the promotor region of the fragile X mental retardation 1 gene (FMR1). As a result, the promotor region often becomes methylated which leads to a deficiency or absence of the FMR1 protein (FMRP). Common characteristics of FXS include mild to severe cognitive impairments in males but less severe cognitive impairment in females. Physical features of FXS include an elongated face, prominent ears, and post-pubertal macroorchidism. Severe obesity in full mutation males is often associated with the Prader-Willi phenotype (PWP) which includes hyperphagia, lack of satiation after meals, and hypogonadism or delayed puberty; however, there is no deletion at 15q11-q13 nor uniparental maternal disomy. Herein, we discuss the molecular mechanisms leading to FXS and the Prader-Willi phenotype with an emphasis on mouse FMR1 knockout studies that have shown the reversal of weight increase through mGluR antagonists. Finally, we review the current medications used in treatment of FXS including the atypical antipsychotics that can lead to weight gain and the research regarding the use of targeted treatments in FXS that will hopefully have a significantly beneficial effect on cognition and behavior without weight gain. PMID- 22043170 TI - Alstrom syndrome: genetics and clinical overview. AB - Alstrom syndrome is a rare autosomal recessive genetic disorder characterized by cone-rod dystrophy, hearing loss, childhood truncal obesity, insulin resistance and hyperinsulinemia, type 2 diabetes, hypertriglyceridemia, short stature in adulthood, cardiomyopathy, and progressive pulmonary, hepatic, and renal dysfunction. Symptoms first appear in infancy and progressive development of multi-organ pathology leads to a reduced life expectancy. Variability in age of onset and severity of clinical symptoms, even within families, is likely due to genetic background.Alstrom syndrome is caused by mutations in ALMS1, a large gene comprised of 23 exons and coding for a protein of 4,169 amino acids. In general, ALMS1 gene defects include insertions, deletions, and nonsense mutations leading to protein truncations and found primarily in exons 8, 10 and 16. Multiple alternate splice forms exist. ALMS1 protein is found in centrosomes, basal bodies, and cytosol of all tissues affected by the disease. The identification of ALMS1 as a ciliary protein explains the range of observed phenotypes and their similarity to those of other ciliopathies such as Bardet-Biedl syndrome.Studies involving murine and cellular models of Alstrom syndrome have provided insight into the pathogenic mechanisms underlying obesity and type 2 diabetes, and other clinical problems. Ultimately, research into the pathogenesis of Alstrom syndrome should lead to better management and treatments for individuals, and have potentially important ramifications for other rare ciliopathies, as well as more common causes of obesity and diabetes, and other conditions common in the general population. PMID- 22043171 TI - A clinical overview of centrosome amplification in human cancers. AB - The turn of the 21st century had witnessed a surge of interest in the centrosome and its causal relation to human cancer development - a postulate that has existed for almost a century. Centrosome amplification (CA) is frequently detected in a growing list of human cancers, both solid and haematological, and is a candidate "hallmark" of cancer cells. Several lines of evidence support the progressive involvement of CA in the transition from early to advanced stages of carcinogenesis, being also found in pre-neoplastic lesions and even in histopathologically-normal tissue. CA constitutes the major mechanism leading to chromosomal instability and aneuploidy, via the formation of multipolar spindles and chromosomal missegregation. Clinically, CA may translate to a greater risk for initiation of malignant transformation, tumour progression, chemoresistance and ultimately, poor patient prognosis. As mechanisms underlying CA are progressively being unravelled, the centrosome has emerged as a novel candidate target for cancer treatment. This Review summarizes mainly the clinical studies performed to date focusing on the mechanisms underlying CA in human neoplasia, and highlights the potential utility of centrosomes in the diagnosis, prognosis and treatment of human cancers. PMID- 22043172 TI - Stability of a long noncoding viral RNA depends on a 9-nt core element at the RNA 5' end to interact with viral ORF57 and cellular PABPC1. AB - Kaposi sarcoma-associated herpesvirus (KSHV) ORF57, also known as Mta (mRNA transcript accumulation), enhances viral intron-less transcript accumulation and promotes splicing of intron-containing viral RNA transcripts. In this study, we identified KSHV PAN, a long non-coding polyadenylated nuclear RNA as a main target of ORF57 by a genome-wide CLIP (cross-linking and immunoprecipitation) approach. KSHV genome lacking ORF57 expresses only a minimal amount of PAN. In cotransfection experiments, ORF57 alone increased PAN expression by 20-30-fold when compared to vector control. This accumulation function of ORF57 was dependent on a structured RNA element in the 5' PAN, named MRE (Mta responsive element), but not much so on an ENE (expression and nuclear retention element) in the 3' PAN previously reported by other studies. We showed that the major function of the 5' PAN MRE is increasing the RNA half-life of PAN in the presence of ORF57. Further mutational analyses revealed a core motif consisting of 9 nucleotides in the MRE-II , which is responsible for ORF57 interaction and function. The 9-nt core in the MRE-II also binds cellular PABPC1, but not the E1B AP5 which binds another region of the MRE-II. In addition, we found that PAN RNA is partially exportable in the presence of ORF57. Together, our data provide compelling evidence as to how ORF57 functions to accumulate a non-coding viral RNA in the course of virus lytic infection. PMID- 22043173 TI - Grafting helps improve photosynthesis and carbohydrate metabolism in leaves of muskmelon. AB - The most important quality for muskmelon (Cucumis melo L.) is their sweetness which is closely related to the soluble sugars content. Leaves are the main photosynthetic organs in plants and thus the source of sugar accumulation in fruits since sugars are translocated from leaves to fruits. The effects of grafting muskmelon on two different inter-specific (Cucurbita maxima*C. moschata) rootstocks was investigated with respect to photosynthesis and carbohydrate metabolism. Grafting Zhongmi1 muskmelon on RibenStrong (GR) or Shengzhen1 (GS) rootstocks increased chlorophyll a, chlorophyll b and chlorophyll a+b content and the leaf area in middle and late developmental stages of the plant compared to the ungrafted Zhongmi1 check (CK). Grafting enhanced the net photosynthesis rate, the stomatal conductance, concentration of intercellular CO(2) and transpiration rate. Grafting influenced carbohydrates contents by changing carbohydrate metabolic enzymes activities which was observed as an increase in acid invertase and neutral invertase activity in the functional leaves during the early and middle developmental stages compared to CK. Grafting improved sucrose phosphate synthase and stachyose synthase activities in middle and late developmental stages, thus translocation of sugars (such as sucrose, raffinose and stachyose) in GR and GS leaves were significantly enhanced. However, compared with CK, translocation of more sugars in grafted plants did not exert feedback inhibition on photosynthesis. Our results indicate that grafting muskmelon on inter-specific rootstocks enhances photosynthesis and translocation of sugars in muskmelon leaves. PMID- 22043174 TI - Sphingobium chlorophenolicum dichlorohydroquinone dioxygenase (PcpA) is alkaline resistant and thermally stable. AB - Dichlorohydroquinone dioxygenase (PcpA) is the ring-cleavage enzyme in the PCP biodegradation pathway in Sphingobium chlorophenolicum strain ATCC 39723. PcpA dehalogenates and oxidizes 2,6-dichlorohydroquinone to form 2 chloromaleylacetate, which is subsequently converted to succinyl coenzyme A and acetyl coenzyme A via 3-oxoadipate. Previous studies have shown that PcpA is highly substrate-specific and only uses 2,6-dichlorohydroquinone as its substrate. In the current study, we overexpressed and purified recombinant PcpA and showed that PcpA was highly alkaline resistant and thermally stable. PcpA exhibited two activity peaks at pH 7.0 and 10.0, respectively. The apparent k(cat) and K(m) were measured as 0.19 +/- 0.01 s(-1) and 0.24 +/- 0.08 mM, respectively at pH 7.0, and 0.17 +/- 0.01 s(-1) and 0.77 +/- 0.29 mM, respectively at pH 10.0. Electron paramagnetic resonance studies showed rapid oxidation of Fe(II) to Fe(III) in PcpA and the formation of a stable radical intermediate during the enzyme catalysis. The stable radical was predicted to be an epoxide type dichloro radical with the unpaired electron density localized on C3. PMID- 22043175 TI - Early exposure to paraquat sensitizes dopaminergic neurons to subsequent silencing of PINK1 gene expression in mice. AB - Environmental exposure, genetic modification, and aging are considered risky for Parkinson's disease (PD). How these risk factors cooperate to induce progressive neurodegeneration in PD remains largely unknown. Paraquat is an herbicide commonly used for weed and grass control. Exposure to paraquat is associated with the increased incidence of PD. In contrast to familial PD, most sporadic PD cases do not have genetic mutation, but may suffer from partial dysfunction of neuron protective genes as aging. Using conditional transgenic RNAi, we showed that temporal silencing of PINK1 expression in adult mice increased striatal dopamine, the phenotype that could not be induced by constitutive gene silencing. Moreover, early exposure to paraquat sensitized dopaminergic neurons to subsequent silencing of PINK1 gene expression, leading to a significant loss of dopaminergic neurons. Our findings suggest a novel pathogenesis of PD: exposure to environmental toxicants early in the life reduces the threshold of developing PD and partial dysfunction of neuron-protective genes later in the life initiates a process of progressive neurodegeneration to cross the reduced threshold of disease onset. PMID- 22043176 TI - Glatiramer acetate treatment increases stability of spinal synapses and down regulates MHC I during the course of EAE. AB - The recent discovery that the major histocompatibility complex of class I (MHC I) expression has a role in the synaptic elimination process, represented an insight into understanding the cross talk between neurons. In the present study, the possibility that glatiramer acetate (GA) treatment influences the MHC class I expression and the synaptic plasticity process in the spinal cord during the course of EAE was investigated. C57BL/6J mice were induced to EAE and submitted to treatment either with a placebo solution or with GA (0.05 mg/animal, subcutaneously, on a daily basis). All the animals were sacrificed at the peak disease (14 days after induction) or at the point of recovery of the clinical signs (21 days after induction). The spinal cords were removed and submitted to immunohistochemical examination, Western blotting and transmission electron microscopy analysis. The results showed that GA treatment was able to decrease synaptic loss during the course of EAE, which correlates with the downregulation of the MHC I complex. The present results reinforce the neuroprotective role of GA treatment, by reducing synaptic loss during the course of the disease. Such action may be associated with the recently described role of MHC I regulation during the synaptic plasticity process. PMID- 22043177 TI - Photoactivation studies of zinc porphyrin-myoglobin system and its application for light-chemical energy conversion. AB - An artificial zinc porphyrin-myoglobin-based photo-chemical energy conversion system, consisting of ZnPP-Mb or ZnPE(1)-Mb as a photosensitizer, NADP(+) as an electron acceptor, and triethanolamine as an electron donor, has been constructed to mimic photosystem I. The photoirradiated product is able to reduce a single electron acceptor protein cytochrome c, but cannot catalyze the two-electron reduction of acetaldehyde by alcohol dehydrogenase, thus demonstrating a single electron transfer mechanism. Furthermore, the artificial system can bifunctionally promote oxidoredox reactions, depending on the presence or absence of a sacrificial electron donor, thus suggesting its potential application in electrochemical regeneration steps involved in chemical transformation and/or energy conversion. PMID- 22043178 TI - Evaluation of DNA Force Fields in Implicit Solvation. AB - DNA structural deformations and dynamics are crucial to its interactions in the cell. Theoretical simulations are essential tools to explore the structure, dynamics, and thermodynamics of biomolecules in a systematic way. Molecular mechanics force fields for DNA have benefited from constant improvements during the last decades. Several studies have evaluated and compared available force fields when the solvent is modeled by explicit molecules. On the other hand, few systematic studies have assessed the quality of duplex DNA models when implicit solvation is employed. The interest of an implicit modeling of the solvent consists in the important gain in the simulation performance and conformational sampling speed. In this study, respective influences of the force field and the implicit solvation model choice on DNA simulation quality are evaluated. To this end, extensive implicit solvent duplex DNA simulations are performed, attempting to reach both conformational and sequence diversity convergence. Structural parameters are extracted from simulations and statistically compared to available experimental and explicit solvation simulation data. Our results quantitatively expose the respective strengths and weaknesses of the different DNA force fields and implicit solvation models studied. This work can lead to the suggestion of improvements to current DNA theoretical models. PMID- 22043179 TI - Electronic health records will transform practice. PMID- 22043180 TI - Why meaningful use matters. PMID- 22043181 TI - Electronic health record certification in oncology: role of the certification commission for health information technology. AB - The transparency and multidisciplinary nature of the CCHIT criteria development process ensure that certification is a meaningful and clinically relevant achievement for an EHR product. PMID- 22043182 TI - Electronic Chemotherapy Order Entry: A Major Cancer Center's Implementation. AB - Implementation of a computerized provider order entry system for complex chemotherapy regimens at a large cancer center required intense effort from a multidisciplinary team of clinical and systems experts with experience in all facets of the chemotherapy process. The online tools had to resemble the paper forms used at the time and parallel the successful established process as well as add new functionality. Close collaboration between the institution and the vendor was necessary. This article summarizes the institutional efforts, challenges, and collaborative processes that facilitated universal chemotherapy computerized electronic order entry across multiple sites during a period of several years. PMID- 22043183 TI - Computerized provider order entry in pediatric oncology: design, implementation, and outcomes. AB - PURPOSE: Pediatric oncology is a challenging environment for computerized provider order entry (CPOE). Our goal was to build on the proven safety features of CPOE and facilitate input of expert clinicians. METHODS: A standard, commercially available CPOE system was implemented throughout the hospital. The design of the pediatric oncology implementation was a collaborative effort by a multidisciplinary team of clinicians and information technology experts. RESULTS: During 9 months of configuration effort, 30 medical logic modules and 110 order sets were developed to support pediatric oncology. The proportion of chemotherapy orders submitted using specific research protocol or standard-of-care order sets increased from 57% to 84% as the number of active order sets grew to 200. The number of medication-related patient safety events decreased 39% after implementation of CPOE in pediatric oncology. Acceptance of the system is high in all clinical disciplines. CONCLUSION: Implementation of CPOE required extensive customization but improved patient safety in this highly complex pediatric oncology environment. PMID- 22043184 TI - Implementation of electronic checklists in an oncology medical record: initial clinical experience. AB - PURPOSE: The quality of any medical treatment depends on the accurate processing of multiple complex components of information, with proper delivery to the patient. This is true for radiation oncology, in which treatment delivery is as complex as a surgical procedure but more dependent on hardware and software technology. Uncorrected errors, even if small or infrequent, can result in catastrophic consequences for the patient. We developed electronic checklists (ECLs) within the oncology electronic medical record (EMR) and evaluated their use and report on our initial clinical experience. METHODS: Using the Mosaiq EMR, we developed checklists within the clinical assessment section. These checklists are based on the process flow of information from one group to another within the clinic and enable the processing, confirmation, and documentation of relevant patient information before the delivery of radiation therapy. The clinical use of the ECL was documented by means of a customized report. RESULTS: Use of ECL has reduced the number of times that physicians were called to the treatment unit. In particular, the ECL has ensured that therapists have a better understanding of the treatment plan before the initiation of treatment. An evaluation of ECL compliance showed that, with additional staff training, > 94% of the records were completed. CONCLUSION: The ECL can be used to ensure standardization of procedures and documentation that the pretreatment checks have been performed before patient treatment. We believe that the implementation of ECLs will improve patient safety and reduce the likelihood of treatment errors. PMID- 22043185 TI - Integrated information systems for electronic chemotherapy medication administration. AB - INTRODUCTION: Chemotherapy administration is a highly complex and distributed task in both the inpatient and outpatient infusion center settings. The American Society of Clinical Oncology and the Oncology Nursing Society (ASCO/ONS) have developed standards that specify procedures and documentation requirements for safe chemotherapy administration. Yet paper-based approaches to medication administration have several disadvantages and do not provide any decision support for patient safety checks. Electronic medication administration that includes bar coding technology may provide additional safety checks, enable consistent documentation structure, and have additional downstream benefits. METHODS: We describe the specialized configuration of clinical informatics systems for electronic chemotherapy medication administration. The system integrates the patient registration system, the inpatient order entry system, the pharmacy information system, the nursing documentation system, and the electronic health record. RESULTS: We describe the process of deploying this infrastructure in the adult and pediatric inpatient oncology, hematology, and bone marrow transplant wards at Vanderbilt University Medical Center. We have successfully adapted the system for the oncology-specific documentation requirements detailed in the ASCO/ONS guidelines for chemotherapy administration. However, several limitations remain with regard to recording the day of treatment and dose number. CONCLUSION: Overall, the configured systems facilitate compliance with the ASCO/ONS guidelines and improve the consistency of documentation and multidisciplinary team communication. Our success has prompted us to deploy this infrastructure in our outpatient chemotherapy infusion centers, a process that is currently underway and that will require a few unique considerations. PMID- 22043186 TI - Patient-physician e-mail communication: the kaiser permanente experience. AB - Kaiser Permanente (KP) is a not-for profit health care organization that provides care for approximately 8.7 million members in nine states and the District of Columbia. In 2004, it began implementation of its current electronic health record (EHR), which by 2010, was in use in all KP regions, in both outpatient and inpatient settings. Over the same period, a suite of online services was also implemented. Among these services was a password-protected e-mail system (referred to as secure messaging) that allowed physicians and patients to communicate electronically. Use of secure messaging has increased rapidly. By 2010, 64% of the 3.6 million KP members in northern California had signed up for online access. In 2010, the 7,000 physicians of Northern California KP received 5.8 million secure messages. Secure messaging has been associated with a decrease in office visits, an increase in measurable quality outcomes (at least in primary care), and excellent patient satisfaction. PMID- 22043187 TI - Outcomes of computerized physician order entry in an electronic health record after implementation in an outpatient oncology setting. AB - PURPOSE: Computerized physician order entry (CPOE) in electronic health records (EHR) has been recognized as an important tool in optimal health care provision that can reduce errors and improve safety. The objective of this study is to describe documentation completeness and user satisfaction of medical charts before and after implementation of an outpatient oncology EHR/ CPOE system in a hospital-based outpatient cancer center within three treatment sites. METHODS: This study is a retrospective chart review of 90 patients who received one of the following regimens between 1999 and 2006: FOLFOX, AC, carboplatin + paclitaxel, ABVD, cisplatin + etoposide, R-CHOP, and clinical trials. Documentation completeness scores were assigned to each chart based on the number of documented data points found out of the total data points assessed. EHR/CPOE documentation completeness was compared with completeness of paper charts orders of the same regimens. A user satisfaction survey of the paper chart and EHR/CPOE system was conducted among the physicians, nurses, and pharmacists who worked with both systems. RESULTS: The mean percentage of identified data points successfully found in the EHR/CPOE charts was 93% versus 67% in the paper charts (P < .001). Regimen complexity did not alter the number of data points found. The survey response rate was 64%, and the results showed that satisfaction was statistically significant in favor of the EHR/CPOE system. CONCLUSION: Using EHR/CPOE systems improves completeness of medical record and chemotherapy order documentation and improves user satisfaction with the medical record system. EHR/CPOE requires constant vigilance and maintenance to optimize patient safety. PMID- 22043188 TI - What Do People Affected by Cancer Think About Electronic Health Information Exchange? Results From the 2010 LIVESTRONG Electronic Health Information Exchange Survey and the 2008 Health Information National Trends Survey. AB - PURPOSE: The Health Information Technology for Economic and Clinical Health (HITECH) Act has placed an emphasis on electronic health information exchange (EHIE). Research on needs of patient, especially those touched by cancer, has been sparse. Here, we present data on preferences for EHIE among those touched by cancer compared with a nationally representative sample of American adults. METHODS: TWO SURVEYS WERE USED: an online survey designed by LIVESTRONG (the Lance Armstrong Foundation) and a dual-frame, nationally representative sample of adults collected through the National Cancer Institute's Health Information National Trends Survey (HINTS). RESULTS: The LIVESTRONG EHIE survey yielded a sample of 8,411 respondents, including 433 currently receiving cancer treatment, 298 living with cancer as a chronic disease, 2,343 post-treatment survivors, and 5,337 with no history of cancer. The HINTS sample consisted of 7,674 respondents representative of the general adult population. Comparisons revealed a strong positive view of the value of EHIE within the cancer-relevant groups, especially among those living with cancer as a chronic disease. Only about half of the general population showed a similar degree of enthusiasm for EHIE. When asked about specific functions for EHRs, respondents valued privacy and security above all, followed by improving care coordination and data sharing between providers. CONCLUSION: These data suggest that the EHIE needs among those touched by cancer may be greater than in the general population. This is particularly important because people affected by cancer are among those who access our health care system most frequently and who have the most at stake. PMID- 22043189 TI - Possibly impossible patients: management of difficult behavior in oncology outpatients. AB - Angry, threatening, or otherwise disruptive behavior by patients can interfere with necessary oncologic treatment, sometimes to the point of rendering continued care impossible. We offer oncology clinicians guidance in dealing with difficult outpatients by discussing the differential diagnosis and multidisciplinary management of treatment-disrupting behavior in the ambulatory oncology setting.We review the existing literature on dealing with difficult patients and present clinical experience at a comprehensive cancer center where a formalized, institutional process for responding to disruptive outpatients has been developed.A structured, multidisciplinary approach to deal with difficult behavior in oncology outpatients can improve care and staff morale. Staff using this approach can identify causes of treatment-disrupting behavior, develop and implement appropriate behavior plans, facilitate communication, address mental health issues, and ensure that decisions to terminate a relationship with a patient are ethical, clinically justified, and supported by due process.In the future, clinical recommendations and institutional guidelines for dealing with difficult patients should be evaluated with more structured, quantitative research. PMID- 22043190 TI - Degree of variability in performance on breast cancer quality indicators: findings from the Florida initiative for quality cancer care. AB - PURPOSE: The Florida Initiative for Quality Cancer Care (FIQCC) comprises 11 Florida practice sites that participate in comprehensive reviews of quality of care specific to patients with cancer. Here, we examined site adherence to performance indicators to assess quality of care for patients with breast cancer (BC). METHODS: Quality indicators were scripted on the basis of accepted guidelines from the Quality Oncology Practice Initiative, National Comprehensive Cancer Network, American College of Surgeons, and site-specific expert panel consensus. Comprehensive chart reviews, including both medical and surgical oncology quality measures, were conducted for patients with BC first seen in 2006 by a medical oncologist at one of the sites. Statistical comparisons were made by the Pearson chi(2) exact test, using Monte Carlo estimation. RESULTS: Charts of 622 patients were reviewed. Of the 34 indicators, seven for medical oncology and four for surgical oncology fell below the 85% level of adherence. A statistically significant difference (P < .001) in variation of performance across the sites was found for the following medical and surgical oncology indicators: documentation of menopausal status, family history, informed consent, planned chemotherapy regimen and flow sheet, American Joint Committee on Cancer staging, HER2/neu status, reporting of margin orientation and inking of the margins, histological grade, having a sentinel lymph node biopsy for invasive BC, and obtaining a mammogram within 14 months of definitive surgery. CONCLUSION: The FIQCC has identified how multiple aspects of BC care can be improved. Findings are being used at the participating institutions to guide quality improvement efforts. PMID- 22043191 TI - Model for a community-based exercise program for cancer survivors: taking patient care to the next level. AB - This article describes the development and refinement of a not-for-profit, community-based exercise program, the Cancer Foundation For Life (CFFL), designed to improve quality of life (QOL) for persons with cancer, regardless of type or stage of disease. Beginning in 2001, policies and procedures were developed, and personnel were hired and trained. Program evaluation measured safety, exercise adherence, demographic variables, and QOL. CFFL had nearly 3,000 referrals and handled more than 66,000 patient encounters in 2010. Financial and social resources for the program have been established through collaboration with existing institutions (churches, cancer centers, hospitals, and community centers), in conjunction with community support. American College of Sports Medicine guidelines presented at the ASCO 2010 meeting recommend exercise for persons with cancer. The CFFL program provides a cost-effective and safe exercise program for persons with all types and stages of cancer that meets these recommended guidelines. PMID- 22043192 TI - Dissemination of Quality-of-Care Research Findings to Breast Oncology Surgeons. AB - PURPOSE: In this era of rapidly evolving clinical knowledge, clinicians need to be aware of current research and how it might affect their practice. The Internet is a widely available, under-assessed tool for providing this information. In this two-phase pilot study, a novel Web site (www.cansortsurgeons.org) was developed to specifically disseminate relevant clinical information to community breast oncology surgeons. METHODS: The first phase targeted a sample of community surgeons identified from Surveillance, Epidemiology, and End Results catchment areas in Los Angeles, CA and Detroit, MI. The second phase broadened availability by linking the site through the American College of Surgeons (ACoS) Commission on Cancer (CoC) homepage. An eight-question, Web-based survey was used to obtain feedback regarding the Web site's utility and potential application to clinical practice. Journal continuing medical education credit was also offered through ACoS. RESULTS: For phase 1, of the 315 community surgeons invited to view the site, 114 (36%) participated in the study and 98 (86%) responded to the survey. Overall, there was a strongly supportive response, with 79 (81%) recommending the site to other clinicians. For phase 2, of the 516 site hits, 411 came from the ACoS site. Only 10 individuals completed the survey during this phase, but all positively endorsed the utility of the site. CONCLUSION: The implication for clinical practice is that the Internet is a useful tool for providing relevant clinical research to providers. In the future, this could be tailored to an individual's needs, aiding synthesis and, hopefully, improving the quality of clinical care. PMID- 22043193 TI - Oncologist-hospital alignment models built to compensate oncologists fairly. AB - Reimbursement for services is down; practice overhead is up; community oncologist take-home income continues to erode-that is a common scenario today. No wonder community oncologists are interested in exploring alignment relationships with hospitals and academic medical centers. It can actually work too: fragmented services can be consolidated; oncologist incomes can be stabilized; communities can be better served. But what can oncologists entering into these relationships expect to be paid for their professional contribution? This article describes approaches to structuring an oncologist-hospital alignment relationship and compensation methodologies applicable to each. PMID- 22043194 TI - A new look at informed consent for cancer clinical trials. AB - Informed consent is fundamental to the conduct of clinical trials. Prospective participants need to be adequately informed and given the opportunity to ask questions and consult with relatives or friends without feeling pressured or rushed. PMID- 22043195 TI - A financial counselor on the practice staff: a win-win. AB - Patients with cancer are often burdened by financial stresses during treatment. The presence of a financial counselor can help alleviate these concerns for both patients and providers. PMID- 22043196 TI - Natural language processing and the oncologic history: is there a match? AB - PURPOSE: The widespread adoption of electronic health records (EHRs) is creating rich databases documenting the cancer patient's care continuum. However, much of this data, especially narrative "oncologic histories," are "locked" within free text (unstructured) portions of notes. Nationwide incentives, ranging from certification (Quality Oncology Practice Initiative) to monetary reimbursement (the Health Information Technology for Economic and Clinical Health Act), increasingly require the translation of these histories into treatment summaries for patient use and into tools to assist in transitions of care. Unfortunately, formulation of treatment summaries from these data is difficult and time consuming. The rapidly developing field of automated natural language processing may offer a solution to this communication problem. METHODS: We surveyed a cross section of providers at Beth Israel Deaconess Medical Center regarding the importance of treatment summaries and whether these were being formulated on a regular basis. We also developed a program for the Informatics for Integrating Biology and the Bedside challenge, which was designed to extract meaningful information from EHRs. The program was then applied to a sample of narrative oncologic histories. RESULTS: The majority of providers (86%) felt that treatment summaries were important, but only 11% actually implemented them. The most common obstacles identified were lack of time and lack of EHR tools. We demonstrated that relevant medical concepts can be automatically extracted from oncologic histories with reasonable accuracy and precision. CONCLUSION: Natural language processing technology offers a promising method for structuring a free-text oncologic history into a compact treatment summary, creating a robust and accurate means of communication between providers and between provider and patient. PMID- 22043197 TI - Effect of an electronic health record on the culture of an outpatient medical oncology practice in a four-hospital integrated health care system: 5-year experience. AB - The electronic health record (EHR) was adopted into the NorthShore University HealthSystem, a four-hospital integrated health system located in suburban Chicago, in 2003. By 2005, all chemotherapy and medicine order entry was conducted through the EHR, completing the incorporation of a fully paperless EHR in our hospital-based oncology practice in both the inpatient and outpatient settings. The use of the EHR has dramatically changed our practice environment by improving efficiency, patient safety, research productivity, and operations, while allowing evaluation of adherence to established quality measures and incorporation of new quality improvement initiatives. The reach of the EHR has been substantial and has influenced every aspect of care at our institution over the short period since its implementation. In this article, we describe subjective and objective measures, outcomes, and achievements of our 5-year EHR experience. PMID- 22043198 TI - Creating a process to standardize regimen order sets within an electronic health record. AB - PURPOSE: US Oncology uses regimen order sets in clinical practice to treat patients. However, the process to assure accuracy and upkeep of these order sets has not been described. The purpose of this project was to evaluate the regimens housed in the electronic health record, iKnowMed, to determine their appropriateness and accuracy. MATERIALS AND METHODS: US Oncology conducted an audit of its standardized regimen library. A utilization review compared chemotherapy regimens in the library and consolidated order sets on the basis of past utilization. Next, internal and external clinical pharmacists were contracted to verify the accuracy, dose, duration, and cycle length of regimens. References cited in the regimen library were evaluated. New or updated references or clinical practice standards were added or modified when necessary. US Oncology corporate pharmacists reviewed the recommendations and discussed findings with an oversight committee. Final proposals were voted on before being incorporated into iKnowMed. An internal database tracking system tool for all reviewed recommendations was created to track and communicate needed changes to the electronic health record. RESULTS: Out of 511 regimen order sets, 51 were recommended for removal or consolidation. Of the remaining 460 regimen order sets, all had some administrative changes. Specifically, 75% had title changes, 14% had cycle-related changes, 31% had reference updates, and 13% had dosing updates. CONCLUSION: Electronic health records systems, such as iKnowMed, can provide standardized order sets for a large oncology network. However, the regimens need to be evaluated routinely using standardized procedures to ensure they are accurate and current. PMID- 22043199 TI - Editorial: crucial role of redox signaling in the regulation of heart health. PMID- 22043200 TI - Modulatory Role of Nitric Oxide/cGMP System in Endothelin-1-Induced Signaling Responses in Vascular Smooth Muscle Cells. AB - Nitric oxide (NO) is an important vasoprotective molecule that serves not only as a vasodilator but also exerts antihypertrophic and antiproliferative effects in vascular smooth muscle cells (VSMC). The precise mechanism by which the antihypertrophic and antiproliferative responses of NO are mediated remains obscure. However, recent studies have suggested that one of the mechanisms by which this may be achieved includes the attenuation of signal transduction pathways responsible for inducing the hypertrophic and proliferative program in VSMC. Endothelin-1 is a powerful vasoconstrictor peptide with mitogenic and growth stimulatory properties and exerts its effects by activating multiple signaling pathways which include ERK 1/2, PKB and Rho-ROCK. Both cGMP-dependent and independent events have been reported to mediate the effect of NO on these pathways leading to its vasoprotective response. This review briefly summarizes some key studies on the modulatory effect of NO on these signaling pathways and discusses the possible role of cGMP system in this process. PMID- 22043201 TI - Mechanisms of the beneficial actions of ischemic preconditioning on subcellular remodeling in ischemic-reperfused heart. AB - Cardiac function is compromised by oxidative stress which occurs upon exposing the heart to ischemia reperfusion (I/R) for a prolonged period. The reactive oxygen species (ROS) that are generated during I/R incur extensive damage to the myocardium and result in subcellular organelle remodeling. The cardiac nucleus, glycocalyx, myofilaments, sarcoplasmic reticulum, sarcolemma, and mitochondria are affected by ROS during I/R injury. On the other hand, brief periods of ischemia followed by reperfusion, or ischemic preconditioning (IPC), have been shown to be cardioprotective against oxidative stress by attenuating the cellular damage and alterations of subcellular organelles caused by subsequent I/R injury. Endogenous defense mechanisms, such as antioxidant enzymes and heat shock proteins, are activated by IPC and thus prevent damage caused by oxidative stress. Although these cardioprotective effects of IPC against I/R injury are considered to be a consequence of changes in the redox state of cardiomyocytes, IPC is considered to promote the production of NO which may protect subcellular organelles from the deleterious actions of oxidative stress. The article is intended to focus on the I/R-induced oxidative damage to subcellular organelles and to highlight the cardioprotective effects of IPC. In addition, the actions of various endogenous cardioprotective interventions are discussed to illustrate that changes in the redox state due to IPC are cardioprotective against I/R injury to the heart. PMID- 22043202 TI - Oxygen Sensing, Cardiac Ischemia, HIF-1alpha and Some Emerging Concepts. AB - Oxygen plays a critical role in the perpetuation and propagation of almost all forms of life. The primary site of cellular oxygen consumption is the mitochondrial electron transport chain and in addition, oxygen is also used as a substrate for various enzymes involved in cellular homeostasis. Although our knowledge of the biochemistry and physiology of oxygen transport is century old, recent development of sophisticated tools of biophysical chemistry revealed that tissue oxygenation and oxygen sensing is a highly evolved process, especially in mammals. Perturbation of normal oxygen supply is associated with diseases like tumorigenesis, myocardial infarction and stroke. Available information suggests that when tissue oxygen supply is limited, mitochondria emanate signals involving reactive oxygen species generation which in turn stabilizes oxygen sensing transcription factor HIF-1. Upon stabilization, HIF-1 elicits necessary genetic response to cope with the diminished oxygen level. In view of such critical role of HIF-1 in cellular oxygen sensing, recently there has been a heightened interest in understanding the biology of HIF-1 in the context of cardiovascular system. The following review describes some of the recent advances in this regard. PMID- 22043203 TI - Indian spices for healthy heart - an overview. AB - Spices were some of the most valuable items of trade in the ancient and medieval world. Herbalist and folk practitioners have used plant remedies for centuries, but only recently have scientist begun to study the powers of common herbs and spices. In the current set-up, the anti-proliferative, anti-hypercholesterolemic, anti-diabetic, anti-inflammatory effects of spices have overriding importance, as the key health concern of mankind nowadays is diabetes, cardio-vascular diseases, arthritis and cancer. Spices or their active compounds could be used as possible ameliorative or preventive agents for these health disorders. Spices are rich in antioxidants, and scientific studies suggest that they are also potent inhibitors of tissue damage and inflammation caused by high levels of blood sugar and circulating lipids. Because spices have very low calorie content and are relatively inexpensive, they are reliable sources of antioxidants and other potential bioactive compounds in diet. This review outlines the role of some spices used in the Indian kitchen for its flavour and taste which are potential to maintain a healthy heart. PMID- 22043205 TI - The DOCA-Salt Hypertensive Rat as a Model of Cardiovascular Oxidative and Inflammatory Stress. AB - Oxidative stress and inflammation are two sides of the same coin that are intricately combined to elicit a chronic pathophysiological stress state, especially as seen in cardiovascular remodelling. In this review, we argue that administration of deoxycorticosterone acetate (DOCA) and sodium chloride to uninephrectomised rats, defined as DOCA-salt hypertensive rats, provides a reliable animal model of oxidative and inflammatory stress in the cardiovascular system. The supporting evidence includes pathophysiological and biochemical changes together with pharmacological responses to synthetic and natural compounds that lower the concentrations of reactive free radical species and that curtail inflammatory responses in the cardiovascular system. PMID- 22043204 TI - Role of differential signaling pathways and oxidative stress in diabetic cardiomyopathy. AB - Diabetes mellitus increases the risk of heart failure independently of underlying coronary artery disease, and many believe that diabetes leads to cardiomyopathy. The underlying pathogenesis is partially understood. Several factors may contribute to the development of cardiac dysfunction in the absence of coronary artery disease in diabetes mellitus. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Hyperglycemia-induced oxidative stress is a major risk factor for the development of micro-vascular pathogenesis in the diabetic myocardium, which results in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium homeostasis and endothelial dysfunction. Diabetes mediated biochemical changes show cross-interaction and complex interplay culminating in the activation of several intracellular signaling molecules. Diabetic cardiomyopathy is characterized by morphologic and structural changes in the myocardium and coronary vasculature mediated by the activation of various signaling pathways. This review focuses on the oxidative stress and signaling pathways in the pathogenesis of the cardiovascular complications of diabetes, which underlie the development and progression of diabetic cardiomyopathy. PMID- 22043206 TI - Modulation of Gi Proteins in Hypertension: Role of Angiotensin II and Oxidative Stress. AB - Guanine nucleotide regulatory proteins (G-proteins) play a key role in the regulation of various signal transduction systems including adenylyl cyclase/cAMP and phospholipase C (PLC)/phosphatidyl inositol turnover (PI). These are implicated in the modulation of a variety of physiological functions such as platelet functions, cardiovascular functions, including arterial tone and reactivity. Several abnormalities in adenylyl cyclase activity, cAMP levels and G proteins have shown to be responsible for the altered cardiac performance and vascular functions observed in cardiovascular disease states. The enhanced or unaltered levels of inhibitory G-proteins (Gialpha-2 and Gialpha-3) and mRNA have been reported in different models of hypertension, whereas Gsalpha levels were shown to be unaltered. These changes in G-protein expression were associated with Gi functions. The enhanced levels of Gialpha proteins precede the development of blood pressure and suggest that overexpression of Gi proteins may be one of the contributing factors for the pathogenesis of hypertension. The augmented levels of vasoactive peptides, including angiotensin II (AngII), were shown to contribute to enhanced expression of Gialpha proteins and associated adenylyl cyclase signaling and thereby increased blood pressure. In addition, enhanced oxidative stress in hypertension due to Ang II may also be responsible for the enhanced expression of Gialpha proteins observed in hypertension. The mechanism by which oxidative stress enhances the expression of Gi proteins appears to be through the activation of mitogen activated protein (MAP) kinase activity. PMID- 22043208 TI - Tissue Factor/Factor FVII Complex Inhibitors in Cardiovascular Disease. Are Things Going Well? AB - Blood coagulation is a complex biological mechanism aimed to avoid bleeding in which a highly regulated and coordinated interplay of specific proteins and cellular components respond quickly to a vascular injury. However, when this mechanisms occurs in the coronary circulation, it has not a "protective" effect, but rather, it plays a pivotal role in determining acute coronary syndromes. Coagulation recognizes Tissue Factor (TF), the main physiological initiator of the extrinsic coagulation pathway, as its starter.Since TF:VIIa complex is the critical point of the blood coagulation cascade, it is a pharmacological attractive issue for the development of agents with anti thrombotic properties that can exert their activity by inhibiting complex formation and/or its catalytic activity. In fact, it is intuitive that an antithrombotic agent able to inhibit this initial step of the coagulation pathway has several theoretical, extremely important, advantages if compared with drugs active downstream the coagulation pathway, such as FXa or thrombin. The present report gives a brief overview of TF pathophysiology, highlighting the most recent advances in the field of inhibitors of the complex TF/VIIa potentially useful in cardiovascular disease. PMID- 22043209 TI - Choosing a revascularization strategy in patients with diabetes and stable coronary artery disease: a complex decision. AB - Diabetes mellitus is associated with well-known increases in cardiovascular morbidity and mortality. In diabetics with stable coronary artery disease, the best therapeutic option is widely discussed. Current studies comparing surgical to percutaneous revascularization have been unable to definitely demonstrate any significant advantage of one strategy over the other regarding the prevention of cardiac death or acute myocardial infarction. Therefore, even taking into account clinical and angiographic information as well as the risks determined by each type of treatment, the decision regarding the best therapeutic strategy in diabetics with stable coronary artery disease is still complex. PMID- 22043210 TI - AMPK - Activated Protein Kinase and its Role in Energy Metabolism of the Heart. AB - Adenosine monophosphate - activated kinase (AMPK) plays a key role in the coordination of the heart's anabolic and catabolic pathways. It induces a cellular cascade at the center of maintaining energy homeostasis in the cardiomyocytes.. The activated AMPK is a heterotrimeric protein, separated into a catalytic alpha - subunit (63kDa), a regulating beta - subunit (38kDa) and a gamma - subunit (38kDa), which is allosterically adjusted by adenosine triphosphate (ATP) and adenosine monophosphate (AMP). The actual binding of AMP to the gamma - subunit is the step which activates AMPK. AMPK serves also as a protein kinase in several metabolic pathways of the heart, including cellular energy sensoring or cardiovascular protection. The AMPK cascade represents a sensitive system, activated by cellular stresses that deplete ATP and acts as an indicator of intracellular ATP/AMP. In the context of cellular stressors (i.e. hypoxia, pressure overload, hypertrophy or ATP deficiency) the increasing levels of AMP promote allosteric activation and phosphorylation of AMPK. As the concentration of AMP begins to increase, ATP competitively inhibits further phosphorylation of AMPK. The increase of AMP may also be induced either from an iatrogenic emboli, percutaneous coronary intervention, or from atherosclerotic plaque rupture leading to an ischemia in the microcirculation. To modulate energy metabolism by phosphorylation and dephosphorylation is vital in terms of ATP usage, maintaining transmembrane transporters and preserving membrane potential. In this article, we review AMPK and its role as an important regulatory enzyme during periods of myocardial stress, regulating energy metabolism, protein synthesis and cardiovascular protection. PMID- 22043207 TI - Lipid rafts and redox regulation of cellular signaling in cholesterol induced atherosclerosis. AB - Redox mediated signaling mechanisms play crucial roles in the pathogenesis of several cardiovascular diseases. Atherosclerosis is one of the most important disorders induced mainly by hypercholesterolemia. Oxidation products and related signaling mechanisms are found within the characteristic biomarkers of atherosclerosis. Several studies have shown that redox signaling via lipid rafts play a significant role in the regulation of pathogenesis of many diseases including atherosclerosis. This review attempts to summarize redox signaling and lipid rafts in hypercholesterolemia induced atherosclerosis. PMID- 22043211 TI - The adult patient with eisenmenger syndrome: a medical update after dana point part I: epidemiology, clinical aspects and diagnostic options. AB - Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death.For a long time, therapy has been limited to symptomatic options or lung or combined heart-lung transplantation. As new selective pulmonary vasodilators have become available and proven to be beneficial in various forms of pulmonary arterial hypertension, this targeted medical treatment has been expected to show promising effects with a delay of deterioration also in Eisenmenger patients. Unfortunately, data in Eisenmenger patients suffer from small patient numbers and a lack of randomized controlled studies.To optimize the quality of life and the outcome, referral of Eisenmenger patients to spezialized centers is required. In such centers, specific interdisciplinary management strategies of physicians specialized on congenital heart diseases and PAH should be warranted. This medical update emphasizes the current diagnostic and therapeutic options for Eisenmenger patients with particularly focussing on epidemiology, clinical aspects and specific diagnostic options. PMID- 22043214 TI - Retraction. PMID- 22043212 TI - The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part II: Medical Treatment - Study Results. AB - Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death.For a long time, therapy has been limited to symptomatic options or lung or combined heart-lung transplantation. As new selective pulmonary vasodilators have become available and proven to be beneficial in various forms of pulmonary arterial hypertension, this targeted medical treatment has been expected to show promising effects with a delay of deterioration also in Eisenmenger patients. Unfortunately, data in Eisenmenger patients suffer from small patient numbers and a lack of randomized controlled studies.To optimize the quality of life and the outcome, referral of Eisenmenger patients to spezialized centers is required. In such centers, specific interdisciplinary management strategies of physicians specialized on congenital heart diseases and PAH should be warranted. This medical update emphasizes the current diagnostic and therapeutic options for Eisenmenger patients with particularly focussing on the medical treatment and corresponding study results. PMID- 22043213 TI - The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part III: Specific Management and Surgical Aspects. AB - Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension and arises on the basis of congenital heart disease with a systemic-to-pulmonary shunt. Due to the chronic slow progressive hypoxemia with central cyanosis, adult patients with the Eisenmenger syndrome suffer from a complex and multisystemic disorder including coagulation disorders (bleeding complications and paradoxical embolisms), renal dysfunction, hypertrophic osteoarthropathy, heart failure, reduced quality of life and premature death.For a long time, therapy has been limited to symptomatic options or lung or combined heart-lung transplantation. As new selective pulmonary vasodilators have become available and proven to be beneficial in various forms of pulmonary arterial hypertension, this targeted medical treatment has been expected to show promising effects with a delay of deterioration also in Eisenmenger patients. Unfortunately, data in Eisenmenger patients suffer from small patient numbers and a lack of randomized controlled studies.To optimize the quality of life and the outcome, referral of Eisenmenger patients to spezialized centers is required. In such centers, specific interdisciplinary management strategies of physicians specialized on congenital heart diseases and PAH should be warranted. This medical update emphasizes the current diagnostic and therapeutic options for Eisenmenger patients with particularly focussing on specific management and surgical aspects. PMID- 22043215 TI - Indications of decreasing human PTS concentrations in North West Russia. AB - BACKGROUND: The Russian Arctic covers an enormous landmass with diverse environments. It inhabits more than 20 different ethnic groups, all of them with various living conditions and food traditions. Indigenous populations with a traditional way of living are exposed to a large number of anthropogenic pollutants, such as persistent organic pollutants (POPs) and toxic metals, mainly through the diet. Human monitoring of persistent organic pollutants (POPs) and heavy metals in the Russian Arctic has only been performed on irregular intervals over the past 15 years, thus, there is still a lack of baseline data from many ethnic groups and geographical regions. The aim of the current study was to investigate concentrations of POPs and toxic metals in three groups of indigenous people from the Russian Arctic. Plasma concentrations of POPs were measured in one of the locations (Nelmin-Nos) in 2001-2003 which gave the unique opportunity to compare concentrations over time in a small Russian arctic community. METHODS: During 2009 and early 2010, 209 blood samples were collected from three different study sites in North West Russia; Nelmin-Nos, Izhma and Usinsk. The three study sites are geographically separated and the inhabitants are expected to have different dietary habits and living conditions. All blood samples were analyzed for POPs and toxic metals. RESULTS: PCB 153 was present in highest concentrations of the 18 PCBs analyzed. p,p'-DDE and HCB were the two most dominating OC pesticides. Males had higher concentrations of PCB 138, 153 and 180 than women and age was a significant predictor of PCB 153, 180, HCB and p,p'-DDD. Males from Izhma had significantly higher concentrations of HCB than males from the other study sites and women from Usinsk had higher concentrations of p,p'-DDE. Parity was a significant predictor of p,p'-DDE. Hg and Pb concentrations increased with increasing age and males had significantly higher concentrations of Pb than women. The study group from Izhma had significantly higher concentrations of Cd when controlling for age and gender and the study group from Usinsk had higher concentrations of Se than the others. Compared to the results from Nelmin-Nos in 2001-2003, a clear decrease in p,p'-DDE concentrations for both women and men was observed. CONCLUSIONS: The current study indicates a significant reduction of several PTSs in human blood samples from North West Russia over the past 10 years. PMID- 22043216 TI - Infant mortality of Sami and settlers in Northern Sweden: the era of colonization 1750-1900. AB - The study deals with infant mortality (IMR) that is one of the most important aspects of indigenous vulnerability. BACKGROUND: The Sami are one of very few indigenous peoples with an experience of a positive mortality transition. OBJECTIVE: Using unique mortality data from the period 1750-1900 Sami and the colonizers in northern Sweden are compared in order to reveal an eventual infant mortality transition. FINDINGS: The results show ethnic differences with the Sami having higher IMR, although the differences decrease over time. There were also geographical and cultural differences within the Sami, with significantly lower IMR among the South Sami. Generally, parity has high explanatory value, where an increased risk is noted for children born as number five or higher among siblings. CONCLUSION: There is a striking trend of decreasing IMR among the Sami after 1860, which, however, was not the result of professional health care. Other indigenous peoples of the Arctic still have higher mortality rates, and IMR below 100 was achieved only after 1950 in most countries. The decrease in Sami infant mortality was certainly an important factor in their unique health transition, but the most significant change occurred after 1900. PMID- 22043217 TI - Climate change and water security with a focus on the Arctic. AB - Water is of fundamental importance for human life; access to water of good quality is of vital concern for mankind. Currently however, the situation is under severe pressure due to several stressors that have a clear impact on access to water. In the Arctic, climate change is having an impact on water availability by melting glaciers, decreasing seasonal rates of precipitation, increasing evapotranspiration, and drying lakes and rivers existing in permafrost grounds. Water quality is also being impacted as manmade pollutants stored in the environment are released, lowland areas are flooded with salty ocean water during storms, turbidity from permafrost-driven thaw and erosion is increased, and the growth or emergence of natural pollutants are increased. By 2030 it is estimated that the world will need to produce 50% more food and energy which means a continuous increase in demand for water. Decisionmakers will have to very clearly include life quality aspects of future generations in the work as impact of ongoing changes will be noticeable, in many cases, in the future. This article will focus on effects of climate-change on water security with an Arctic perspective giving some examples from different countries how arising problems are being addressed. PMID- 22043219 TI - Understanding the mosaic: health services and policy research in Canada. PMID- 22043218 TI - Facing the limit of resilience: perceptions of climate change among reindeer herding Sami in Sweden. AB - BACKGROUND: The Arctic area is a part of the globe where the increase in global temperature has had the earliest noticeable effect and indigenous peoples, including the Swedish reindeer herding Sami, are amongst the first to be affected by these changes. OBJECTIVE: To explore the experiences and perceptions of climate change among Swedish reindeer herding Sami. STUDY DESIGN: In-depth interviews with 14 Swedish reindeer herding Sami were performed, with purposive sampling. The interviews focused on the herders experiences of climate change, observed consequences and thoughts about this. The interviews were analysed using content analysis. RESULTS: One core theme emerged from the interviews: facing the limit of resilience. Swedish reindeer-herding Sami perceive climate change as yet another stressor in their daily struggle. They have experienced severe and more rapidly shifting, unstable weather with associated changes in vegetation and alterations in the freeze-thaw cycle, all of which affect reindeer herding. The forecasts about climate change from authorities and scientists have contributed to stress and anxiety. Other societal developments have lead to decreased flexibility that obstructs adaptation. Some adaptive strategies are discordant with the traditional life of reindeer herding, and there is a fear among the Sami of being the last generation practising traditional reindeer herding. CONCLUSIONS: The study illustrates the vulnerable situation of the reindeer herders and that climate change impact may have serious consequences for the trade and their overall way of life. Decision makers on all levels, both in Sweden and internationally, need improved insights into these complex issues to be able to make adequate decisions about adaptive climate change strategies. PMID- 22043220 TI - The TSX Gives a Short Course in Health Economics: It's the Prices, Stupid! AB - The fall in Shoppers Drug Mart shares last April 8 gave a crystal-clear demonstration of the link between health expenditures and health incomes. Reacting (finally) to the excessive retail prices of generic drugs, the Ontario government effectively halved the rate of reimbursement of ingredient costs and banned the "professional allowances" (kickbacks) paid to pharmacies by generic manufacturers. Taxpayers and private payers will save hundreds of millions of dollars, and pharmacy revenues will fall by an equivalent amount. Patients will still get their drugs, with no loss of quantity, quality or even convenience; no one's health is threatened. But investor profits will fall. There are similar savings opportunities throughout the health system. Health costs are primarily a political, not an economic, problem. PMID- 22043221 TI - The commercialization of genomic research in Canada. AB - The commercialization of academic research has been promoted by North American policy makers for over 30 years as a means of increasing university financing and to ensure that promising research would eventually find its way to the marketplace. The following issues paper constitutes a reflection on the impact of the Canadian commercialization framework on academic research in the field of genomics. It was written following two workshops and two independent studies organized by academic groups in Quebec (Centre of Genomics and Policy) and Alberta (Health Law Institute). The full sets of recommendations are available upon request to the authors. PMID- 22043222 TI - Understanding the Unattached Population in Ontario: Evidence from the Primary Care Access Survey (PCAS). AB - To measure primary care access on an ongoing basis, the Ontario Ministry of Health and Long-Term Care implemented the Primary Care Access Survey (PCAS) in 2006. The PCAS, a cross-sectional telephone survey, samples approximately 8,400 Ontario adults each year. It collects information on access to a family doctor, use of services, health status and socio-demographics. Analysis of the 2007-2008 PCAS (n=16,560) shows that 7.1% of Ontario's adults were without a family doctor (i.e., unattached). The attached and unattached populations differed on socio demographic and health characteristics. Emergency department use was similar between the two groups, but walk-in clinic use was higher among the unattached. The unattached were less likely to have used care for immediate issues but accessed care in a more timely fashion than the attached. This initial exploration of the PCAS provides a better understanding of some of the differences between the attached and unattached populations in Ontario. PMID- 22043223 TI - Listening for prescriptions: a national consultation on pharmaceutical policy issues. AB - OBJECTIVES AND METHODS: Pharmaceutical policy is an increasingly costly, essential and challenging component of health system management. We sought to identify priority pharmaceutical policy issues in Canada and to translate them into research priorities using key informant interviews, stakeholder surveys and a deliberative workshop. RESULTS: WE FOUND CONSENSUS ON OVERARCHING POLICY GOALS: to provide all Canadians with equitable and sustainable access to necessary medicines. We also found widespread frustration that many key pharmaceutical policy issues in Canada - including improving prescription drug financing and pricing - have been persistent challenges owing to a lack of policy coordination. The coverage of extraordinarily costly medicines for serious conditions was identified as a rapidly emerging policy issue. CONCLUSION: Targeted research and knowledge translation activities can help address key policy issues and, importantly, challenges of policy coordination in Canada and thereby reduce inequity and inefficiency in policy approaches and outcomes. PMID- 22043224 TI - Does Receiving Clinical Preventive Services Vary across Different Types of Primary Healthcare Organizations? Evidence from a Population-Based Survey. AB - OBJECTIVE: To measure the association between primary healthcare (PHC) organizational types and patient coverage for clinical preventive services (CPS). METHOD: Study conducted in Quebec (2005), including a population-based survey of patients' experience of care (N=4,417) and a survey of PHC clinics. OUTCOME MEASURES: Patient-reported CPS delivery rates and CPS coverage scores. Multiple logistic regressions used to assess factors associated with higher probability of receiving CPS. RESULTS: CPS delivery rates were higher among patients with a regular source of PHC. Higher CPS score was associated with having a public (OR 1.79; 95% CI 1.35-2.37) or mixed (OR 1.22; 95% CI 1.01-1.48) type of organization as source of PHC compared to a private one, and having had a high number of visits to the regular source of PHC in the past two years (<=6: OR 1.83; 95% CI 1.41-2.38) compared to a single visit. CONCLUSION: Public and mixed PHC organizations seem to perform better. CPS delivery is strongly associated with having a regular source of care. PMID- 22043225 TI - Mapping health services and policy research settings in Canada: following the money, the publications and the interest. AB - While health services and policy research (HSPR) has an established footing in traditional research settings (e.g., universities, hospitals, research institutes) in Canada, its presence in other research settings (e.g., government agencies, regional health authorities, charitable organizations) is emergent and less well understood. Drawing on data from the Canadian Institutes of Health Research, the Canadian Health Services Research Foundation, two Canadian HSPR focused journals (Healthcare Policy and Healthcare Management Forum) and the Canadian Association of Health Services and Policy Research, we mapped HSPR settings based on three different measures: (1) HSPR-related funding, (2) authorship in Canadian HSPR-focused journals and (3) membership in a professional HSPR association. Our findings suggest that while a significant proportion of HSPR is directly linked to non-traditional research settings, the nature and extent of HSPR activity in those settings are unclear. PMID- 22043226 TI - Moral Distress among Healthcare Managers: Conditions, Consequences and Potential Responses. AB - Moral distress - the physical and emotional response to feeling prevented from carrying out ethically proper action - can have serious consequences for health professionals and healthcare organizations. We investigated perceived moral distress qualitatively with managers in two BC health authorities.RESPONDENTS DESCRIBED CONDITIONS UNDER WHICH THEY EXPERIENCED DISTRESS: when they set priorities within highly resource-constrained environments, when they observed inequities between budget allocations and management responsibilities, and when organizational priorities did not align with their personal values. When coping proved insufficient, managers would respond by leaving positions, organizations or the healthcare field altogether.Respondents asked for leadership development and the creation of spaces in which moral distress could be openly discussed. However, formal training in priority setting did not appear to be helpful on its own. Rather, it increased managers' awareness of the ethical dimensions of resource allocation without (in this instance) entrenching supports that would help them resolve these concerns. PMID- 22043227 TI - A comparison of drug coverage in alberta before and after the introduction of the national common drug review process. AB - OBJECTIVE: The integration of the Common Drug Review (CDR) was a substantial change for Canada's public drug plans. Detailed comparisons of time-to-listing and proportion of medications covered by the province of Alberta's drug plans within the context of the CDR process have not been rigorously conducted. METHODS: New drugs approved by Health Canada were identified five years prior to the CDR's first recommendation (May 2004) and five years after. The time-to listing and proportion of new drugs covered on the Alberta Health and Wellness Drug Benefit List (AHWDBL) was compared between these periods. The level of agreement between CDR recommendations and coverage in Alberta was calculated using a kappa score. RESULTS: Two hundred and twenty new drugs were identified and met the study eligibility criteria (118 pre-CDR, 102 post-CDR). The median time-to-listing was 312 vs. 524 days in the pre-CDR and post-CDR periods, respectively, with the difference largely driven by time from notice of compliance (NOC) to the CDR recommendation. The level of agreement between 73 drugs with CDR recommendations and coverage in Alberta was fair (kappa 0.55). CONCLUSION: Following the implementation of the CDR, the proportion of drugs covered has decreased and overall median time-to-listing of new drugs has increased in the province of Alberta. For drugs listed on the AHWDBL, the proportion of time attributable to the CDR process (NOC to CDR recommendation) was 63% of the overall time-to-listing. PMID- 22043228 TI - The LUCK study: Laxative Usage in patients with GP-diagnosed Constipation in the UK, within the general population and in pregnancy. An epidemiological study using the General Practice Research Database (GPRD). AB - BACKGROUND: Despite the high prevalence of constipation and its related public health implications, there is relatively little research available on the condition from large epidemiological studies. The aim of this study was to investigate the epidemiology of general practitioner (GP)-diagnosed constipation and the prescribing trends for laxatives in the UK, within the general population and during pregnancy. METHODS: A cohort study for the period from 2005 to 2009 was performed using the UK primary care database (General Practice Research Database), which contains information on over 3 million individuals. RESULTS: The prevalence of GP-diagnosed constipation ranged from 12 per 1000 persons in 2005 (0.012 per person year) to 12.8 per 1000 in 2009 (0.013 per person year). The prevalence was almost twice as high in women as in men, and was higher in older patients. In 2005 the most commonly prescribed laxatives were lactulose (37%), senna (26%), macrogol (19%), ispaghula (6%), docusate sodium (5%), bisacodyl (4%) and glycerol suppositories (2%). By 2009, this pattern had changed: macrogol (31%), lactulose (29%), senna (22%), ispaghula (5%), docusate sodium (6%), bisacodyl (3%) and glycerol suppositories (3%). In pregnancy, lactulose accounted for 81% of laxative use in 2005, falling to 64% by 2009. In contrast, macrogol use in pregnancy rose from 13% in 2005 to 32% in 2009. CONCLUSIONS: GP-diagnosed constipation is common, accounting for a large number of consultations. Laxative prescribing trends have changed over the 5-year study period, prescriptions for macrogol becoming increasingly common and prescriptions for lactulose and senna less common. Macrogol also appears to have been replacing lactulose for treating constipation in pregnant women. PMID- 22043229 TI - Management of colonic diverticular disease with poorly absorbed antibiotics and other therapies. AB - Colonic diverticular disease is common in Western countries and its prevalence increases with age. The large majority of patients (80-85%) will remain entirely asymptomatic throughout their life. In symptomatic cases, most patients will have diverticulosis without inflammation while the remainder will have diverticulitis with or without complications. About 1-2% will require hospitalization and 0.5% will require surgery. Factors predicting the development of symptoms remain to be identified. However, it is generally recognized that diverticular disease is probably related to complex interactions between colon structure, intestinal motility, diet, and genetic features. Epidemiologic studies have demonstrated an association between diverticulosis and diets that are low in fiber and high in refined carbohydrates. Although the causes of symptom development are still unclear, it is thought that previous episodes of intestinal inflammation may play a role. Changes in intestinal microflora could be one of the putative mechanisms responsible for low-grade inflammation. In patients with uncomplicated diverticulosis, a diet abundant in fruit and vegetables is recommended. The current therapeutic approaches in preventing recurrence of symptoms are based on nonabsorbable antibiotics, mesalazine, and/or probiotics. Cyclic rifaximin administration seems to be an adequate approach to relieving symptoms and preventing acute diverticulitis in patients with symptomatic diverticulosis. PMID- 22043230 TI - Certolizumab pegol for the treatment of Crohn's disease. AB - In this article we provide a contemporary overview of available clinical data on certolizumab pegol, a pegylated anti-tumor necrosis factor (TNF) alpha agent that comprises a uniquely small protein, and its emerging role as a therapy for Crohn's disease (CD). The results from a comprehensive clinical trial program suggest that certolizumab pegol offers rapid and sustained remission of moderate to severe CD. Certolizumab pegol is an effective and well-tolerated therapy both in patients who have already received biologics and in patients who are anti-TNF naive. Benefits of therapy include a stable dosing regimen, which allows for rapid induction of a clinical response followed by long-term maintenance of response and remission under one fixed dose. Treatment with certolizumab pegol has been shown to improve function and quality of life in patients with CD, and insights into the potential mechanisms by which certolizumab pegol effects a response in CD suggest that this agent may have the potential to slow or even modify disease progression. Early therapy is particularly effective and could help control CD progression and lessen the burden of disease on patients. PMID- 22043232 TI - Peroxisome proliferator-activated receptors and hepatitis C virus. AB - The prevalence of type 2 diabetes mellitus and insulin resistance are higher among people chronically infected with hepatitis C (CHC) when compared with the general population and people with other causes of chronic liver disease. Both insulin resistance and diabetes are associated with adverse outcomes across all stages of CHC, including the liver transplant population. CHC is also associated with the development of hepatic steatosis, a common histological feature present in approximately 55% (32-81%) of cases. There is a complex interrelationship between insulin resistance and hepatic steatosis and both are postulated to aggravate each other. The peroxisome proliferator-activated receptors (PPARs) are nuclear factors involved in the regulation of glucose, lipid homeostasis, inflammatory response, cell differentiation, and cell cycle. The relationship between hepatitis C virus replication and PPARs has been the focus of recent study. Given the availability of potent agonists, PPARs may represent a novel pharmacological target in the treatment of CHC. PMID- 22043231 TI - Current status of novel antifibrotic therapies in patients with chronic liver disease. AB - Fibrosis accumulation is a dynamic process resulting from a wound-healing response to acute or chronic liver injury of all causes. The cascade starts with hepatocyte necrosis and apoptosis, which instigate inflammatory signaling by chemokines and cytokines, recruitment of immune cell populations, and activation of fibrogenic cells, culminating in the deposition of extracellular matrix. These key elements, along with pathways of transcriptional and epigenetic regulation, represent fertile therapeutic targets. New therapies include drugs specifically designed as antifibrotics, as well as drugs already available with well established safety profiles, whose mechanism of action may also be antifibrotic. At the same time, the development of noninvasive fibrogenic markers, and techniques (e.g. fibroscan), as well as combined scoring systems incorporating serum and clinical features will allow improved assessment of therapy response. In aggregate, the advances in the elucidation of the biology of fibrosis, combined with improved technologies for assessment will provide a comprehensive framework for design of antifibrotics and their analysis in well-designed clinical trials. These efforts may ultimately yield success in halting the progression of, or reversing, liver fibrosis. PMID- 22043233 TI - Obesity and bariatrics for the endoscopist: new techniques. AB - Obesity and its associated conditions, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions. Gastrointestinal weight loss surgery (GIWLS) shows the most promise in achieving significant and sustained weight loss and diabetes resolution. However, a large mismatch exists between the magnitude of the obesity epidemic and the number of surgical procedures performed to produce a significant shift in the distribution of obesity on a population level. This mismatch is fueled by high surgical costs, morbidity and mortality associated with surgical interventions, and the fact that the greatest public health burden of obesity comes from those around the center of the population body mass index distribution with mild to moderate obesity, rather than those at the distribution tail with severe obesity that GIWLS targets. New endoscopic methods, capitalizing on advances in our understanding of the physiological mechanisms by which GIWLS works, are developing to provide viable alternatives in the treatment of bariatric surgical complications, and for the primary treatment of obesity. These methods may have the added advantage of reduced invasiveness, reversibility, cost-effectiveness, and applicability to a larger segment of the population with moderate obesity. PMID- 22043235 TI - Rapid generation of in vitro multicellular spheroids for the study of monoclonal antibody therapy. AB - Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates and are difficult to study in vitro. Cells cultured as monolayers typically exhibit less resistance to therapy than those grown in vivo. Therefore, it is important to develop an alternative research model that better represents in vivo tumors. We have developed a protocol to produce multicellular spheroids, a simple and more relevant model of in vivo tumors that allows for further investigations of the microenvironmental effects on drug penetration and tumor cell killing. The protocol is used to produce in vitro three-dimensional tumor spheroids from established human cancer cell lines and primary cancer cells isolated from patients without the use of any extracellular components. To study the ability of tumor-targeting immunoconjugates to penetrate these tumor spheroids in vitro, we have used an immunotoxin targeting mesothelin, a surface protein expressed in malignant mesotheliomas. This method for producing consistent, reproducible 3D spheroids may allow for improved testing of novel monoclonal antibodies and other agents for their ability to penetrate solid tumors for cancer therapy. PMID- 22043236 TI - Regulatory Effects of microRNA-92 (miR-92) on VHL Gene Expression and the Hypoxic Activation of miR-210 in Clear Cell Renal Cell Carcinoma. AB - BACKGROUND & AIMS: In order to understand the role of miRNAs in renal tumorigenesis, we undertook a stepwise approach that included a comprehensive differential miRNA expression analysis for the most common histological subtypes of human renal neoplasms appearing in either sporadic or hereditary forms. We also aimed to test the hypothesis that microRNAs can act as an alternative mechanism of VHL gene inactivation and therefore might be correlated with tumorigenesis in ccRCC. Finally, we wanted to explore whether the well-known hypoxic activation of ccRCC is followed by a specific pattern of miRNA expression. METHODS: Tumor and normal adjacent kidney parenchyma from patients with RCC were tested for microRNA expression. Twenty cases of different histologies were used for profiling by PCR miRNA arrays. For validation, a separate cohort of samples used to test specifically miR92a expression and its involvement in VHL gene mRNA silencing. Finally, miR210 as a marker of hypoxia was evaluated. Expression values were correlated with important clinicopathologic features from the patients. RESULTS: We identified unique miRNA expression signatures for each histologic subtype of kidney tumors. Expression values for downregulated miRNAs ranged from 0.3-fold (in VHL-clear cell RCC) up to 0.393 fold (in papillary type II (HLRCC) tumors). For the upregulated miRNAs, fold changes ranged from 2.1 up to 290-fold. Specific patterns together with type specific profiles were observed. Twenty-three miRNAs were found to be differentially expressed in both sporadic and VHL-dependent ccRCC. Sporadic clear cell tumors showed a unique pattern of 14-miRNA that were absent from the VHL dependent tumors. These also showed 15 miRNAs specific to the hereditary type. Common miRNAs to both sporadic and hereditary forms included miR-92a and miR-210. For miR-92a, and a striking inverse correlation with VHL mRNA levels was found. For the hypoxia-regulated miR-210, clear cell tumors showed significantly higher expression levels when compared to tumor of non-clear cell histology (9.90-fold vs. 1.36, p<0.001). CONCLUSIONS: microRNA expression seems to be involved in every step of RCC pathogenesis: both as an element for tumor development as well as a consequence of or in response to the initial malignant transformation and part of tumor progression. Our data show consistent disregulation of miRNAs in human kidney cancer, some of which are potentially involved in critical gene silencing in RCC and others that are activated as part of the pathophysiological response in these tumors. PMID- 22043237 TI - Dactinomycin-induced Hepatic Sinusoidal Obstruction Syndrome Responding to Treatment with N-acetylcysteine. AB - Hepatic sinusoidal obstruction syndrome is commonly described in pediatric oncology as a complication of chemotherapy. It has also been occasionally reported in adult cancer patients. Treatment is largely supportive with fluid restriction. A 16-month-old girl with stage II Wilms tumor receiving post nephrectomy chemotherapy with dactinomycin and vincristine developed hepatic sinusoidal obstruction syndrome with painful hepatomegaly, ascites with significant weight gain, grossly deranged liver function, severe thrombocytopenia, and reversal of blood flow in the portal vein on Doppler sonography. Treatment with N-acetylcysteine was followed by complete resolution of clinical signs and amelioration of laboratory abnormalities within 72 hours of treatment. N-acetylcysteine is a safe and probably an effective treatment for dactinomycin-induced hepatic sinusoidal obstructive syndrome. PMID- 22043239 TI - Synthesis of enantiomerically enriched (R)-C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine. AB - The method of Kouklovsky and coworkers for the enantioselective alkylation of cyclic N-naphthoyl derivatives of amino acids was used to introduce a (13)C label into one of the two enantiotopic methyl groups of 2-aminoisobutyric acid (Aib) by retentive alkylation of L-alanine with (13)CH(3)I. Conditions were identified for optimization of yield and enantiomeric purity, and the absolute configuration of the labelled product was established. PMID- 22043238 TI - Parathyroid carcinoma: a review with three illustrative cases. AB - Parathyroid carcinoma is a rare disease, which accounts for less than 1% of all case of primary hyperparathyroidism and is usually not detected until the time of surgery or thereafter. For most patients preoperative staging is not available. A radical excision remains the standard management; the place of adjuvant radiotherapy is not well established yet. Local recurrence and/or the metastases are unfortunately frequent. The present paper presents an up to date review of the literature illustrated by three clinical cases. PMID- 22043240 TI - Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles. AB - Pyrazolidinones were prepared in a two-step sequence starting from alpha hydrazonocarboxylic acids. After a four-component Ugi coupling, the resulting hydrazone was engaged in a copper triggered [3 + 2] cycloaddition/aerobic oxidation cascade. PMID- 22043241 TI - Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis. AB - A variety of ortho,ortho'-disubstituted hydrobenzoin derivatives are readily accessible through a directed ortho,ortho'-dimetalation strategy in which the alcohol functions in hydrobenzoin are deprotonated by n-BuLi and the resulting lithium benzyl alkoxides serve as directed metalation groups. The optimization and scope of this reaction are discussed, and the utility of this process is demonstrated in the one-pot preparation of a number of chiral diols as well as a short synthesis of the chiral ligand Vivol. PMID- 22043242 TI - Cyclization of 5-hexynoic acid to 3-alkoxy-2-cyclohexenones. AB - The one-pot cyclization of 5-hexynoic acid to produce 3-alkoxy-2-cyclohexenones proceeds in good yields (58-90%). 3-Hexynoic acid was converted to its acyl chloride with the aid of oxalyl chloride and was cyclized to 3-chloro-2 cyclohexenone upon addition of indium(III) chloride. Subsequent addition of alcohol nucleophiles led to the desired 3-alkoxy-2-cyclohexenones. PMID- 22043243 TI - Carbamate-directed benzylic lithiation for the diastereo- and enantioselective synthesis of diaryl ether atropisomers. AB - Diaryl ethers carrying carbamoyloxymethyl groups may be desymmetrised enantio- and diastereoselectively by the use of the sec-BuLi-(-)-sparteine complex in diethyl ether. Enantioselective deprotonation of one of the two benzylic positions leads to atropisomeric products with ca. 80:20 e.r.; an electrophilic quench typically provides functionalised atropisomeric diastereoisomers in up to 97:3 d.r. PMID- 22043244 TI - PEG-embedded KBr(3): A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines. AB - PEG-embedded potassium tribromide ([K(+)PEG]Br(3) (-)) was found to be an efficient and recyclable catalyst for the synthesis of functionalized piperidines in high yields in a one step, three component coupling between aldehyde, amine and beta-keto ester. At the end of the reaction the [K(+)PEG]Br(3) (-) was readily regenerated from the reaction mixture by treating the residue containing [K(+)PEG]Br(-) with molecular bromine. PMID- 22043245 TI - A new phenylethyl alkyl amide from the Ambrostoma quadriimpressum Motschulsky. AB - A new phenylethyl alkyl amide, (10R)-10-hydroxy-N-phenethyloctadecanamide (1), was isolated from the beetle Ambrostoma quadriimpressum Motschulsky. The structure of the amide was determined by NMR and MS. The absolute configuration of compound 1 was confirmed by an asymmetric total synthesis, which was started from L-glutamic acid. The construction of the aliphatic chain was accomplished by the selective protection of the hydroxy groups and two-time implementation of the Wittig olefination reaction. PMID- 22043246 TI - Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids. AB - This paper reviews the current trends in the combined use of supported catalytic systems, either on solid supports or in liquid phases and supercritical fluids (scFs), to develop selective and enantioselective chemical transformations under continuous and semi-continuous flow conditions. The results presented have been selected to highlight how the combined use of those two elements can contribute to: (i) Significant improvements in productivity as a result of the enhanced diffusion of substrates and reagents through the interfaces favored by the scF phase; (ii) the long term stability of the catalytic systems, which also contributes to the improvement of the final productivity, as the use of an appropriate immobilization strategy facilitates catalyst isolation and reuse; (iii) the development of highly efficient selective or, when applicable, enantioselective chemical transformations. Although the examples reported in the literature and considered in this review are currently confined to a limited number of fields, a significant development in this area can be envisaged for the near future due to the clear advantages of these systems over the conventional ones. PMID- 22043247 TI - Translation of microwave methodology to continuous flow for the efficient synthesis of diaryl ethers via a base-mediated S(N)Ar reaction. AB - Whilst microwave heating has been widely demonstrated as a synthetically useful tool for rapid reaction screening, a microwave-absorbing solvent is often required in order to achieve efficient reactant heating. In comparison, microreactors can be readily heated and pressurised in order to "super-heat" the reaction mixture, meaning that microwave-transparent solvents can also be employed. To demonstrate the advantages associated with microreaction technology a series of S(N)Ar reactions were performed under continuous flow by following previously developed microwave protocols as a starting point for the investigation. By this approach, an automated microreaction platform (Labtrix((r)) S1) was employed for the continuous flow synthesis of diaryl ethers at 195 degrees C and 25 bar, affording a reduction in reaction time from tens of minutes to 60 s when compared with a stopped-flow microwave reactor. PMID- 22043249 TI - Combination of gold catalysis and Selectfluor for the synthesis of fluorinated nitrogen heterocycles. AB - We herein report the synthesis of 3-fluoro-2-methylene-pyrrolidine (3a) and piperidine (3b) from 1,5- and 1,6-aminoalkynes, respectively, using a combination of a gold-catalyzed hydroamination reaction followed by electrophilic trapping of an intermediate cyclic enamine by Selectfluor. Careful attention was paid to the elucidation of the mechanism and Selectfluor was suggested to play the double role of promoting the oxidation of gold(I) to a gold(III) active species and also the electrophilic fluorination of the enamine intermediates. PMID- 22043248 TI - Efficient syntheses of 25,26-dihydrodictyostatin and 25,26-dihydro-6-epi dictyostatin, two potent new microtubule-stabilizing agents. AB - The dictyostatins are powerful microtubule-stabilizing agents that have shown antiproliferative activity against a variety of human cancer cell lines. Two highly active analogs of dictyostatin, 25,26-dihydrodictyostatin and 25,26 dihydro-6-epi-dictyostatin, were prepared by a new streamlined total synthesis route. Three complete carbon fragments were prepared to achieve maximum convergency. These were coupled by a Horner-Wadsworth-Emmons reaction sequence and an esterification. A late stage Nozaki-Hiyama-Kishi reaction was then used to form the 22-membered macrolide. The stereoselectivity of this reaction depended on the configurations of the nearby stereocenter at C6. PMID- 22043250 TI - Amines as key building blocks in Pd-assisted multicomponent processes. AB - In the last few years, palladium-mediated three-component synthesis has emerged as an important synthetic methodology to gain access to nitrogen-containing structures. The latest developments in this area are discussed in this review. PMID- 22043251 TI - Manganese dioxide mediated one-pot synthesis of methyl 9H-pyrido[3,4-b]indole-1 carboxylate: Concise synthesis of alangiobussinine. AB - The carboline ring system is an important pharmacophore found in a number of biologically important targets. Development of synthetic routes for the preparation of these compounds is important in order to prepare a range of analogues containing the carboline heterocyclic moiety. A manganese dioxide mediated one-pot method starting with an activated alcohol and consisting of alcohol oxidation, Pictet-Spengler cyclisation, and oxidative aromatisation, offers a convenient process that allows access to beta-carbolines. This one-pot process for the preparation of methyl 9H-pyrido[3,4-b]indole-1-carboxylate has subsequently been used as the key step in the synthesis of alangiobussinine and a closely related analogue. PMID- 22043252 TI - Continuous preparation of carbon-nanotube-supported platinum catalysts in a flow reactor directly heated by electric current. AB - In this contribution we present for the first time a continuous process for the production of highly active Pt catalysts supported by carbon nanotubes by use of an electrically heated tubular reactor. The synthesized catalysts show a high degree of dispersion and narrow distributions of cluster sizes. In comparison to catalysts synthesized by the conventional oil-bath method a significantly higher electrocatalytic activity was reached, which can be attributed to the higher metal loading and smaller and more uniformly distributed Pt particles on the carbon support. Our approach introduces a simple, time-saving and cost-efficient method for fuel cell catalyst preparation in a flow reactor which could be used at a large scale. PMID- 22043253 TI - Development of the titanium-TADDOLate-catalyzed asymmetric fluorination of beta ketoesters. AB - Titanium-based Lewis acids catalyze the alpha-fluorination of beta-ketoesters by electrophilic N-F-fluorinating reagents. Asymmetric catalysis with TADDOLato titanium(IV) dichloride (TADDOL = alpha,alpha,alpha',alpha'-tetraaryl-(1,3 dioxolane-4,5-diyl)-dimethanol) Lewis acids produces enantiomerically enriched alpha-fluorinated beta-ketoesters in up to 91% enantiomeric excess, with either F TEDA (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)) in acetonitrile solution or NFSI (N fluorobenzenesulfonimide) in dichloromethane solution as fluorinating reagents. The effects of various reaction parameters and of the TADDOL ligand structure on the catalytic activity and enantioselectivity were investigated. The absolute configuration of several fluorination products was assigned through correlation. Evidence for ionization of the catalyst complex by chloride dissociation, followed by generation of titanium beta-ketoenolates as key reaction intermediates, was obtained. Based on the experimental findings, a general mechanistic sketch and a steric model of induction are proposed. PMID- 22043254 TI - Wireless Coexistence and EMC of Bluetooth and 802.11b Devices in Controlled Laboratory Settings. AB - This paper presents experimental testing that has been performed on wireless communication devices as victims of electromagnetic interference (EMI). Wireless victims included universal serial bus (USB) network adapters and personal digital assistants (PDAs) equipped with IEEE 802.11b and Bluetooth technologies. The experimental data in this paper was gathered in an anechoic chamber and a gigahertz transverse electromagnetic (GTEM) cell to ensure reliable and repeatable results. This testing includes: Electromagnetic compatibility (EMC) testing performed in accordance with IEC 60601-1-2, an in-band sweep of EMC testing, and coexistence testing. The tests in this study show that a Bluetooth communication was able to coexist with other Bluetooth devices with no decrease in throughput and no communication breakdowns. However, testing revealed a significant decrease in throughput and increase in communication breakdowns when an 802.11b source is near an 802.11b victim. In a hospital setting decreased throughput and communication breakdowns can cause wireless medical devices to fail. It is therefore vital to have an understanding of the effect EMI can have on wireless communication devices. PMID- 22043255 TI - Minimally invasive treatment of moderate lumbar spinal stenosis with the superion interspinous spacer. AB - PURPOSE: We evaluated the safety and effectiveness of the minimally invasive Superion((r)) Interspinous Spacer (VertiFlex, Inc., San Clemente, CA) in patients with moderate LSS. METHODS: This single-arm prospective study enrolled 121 patients with moderate LSS between February 2008 and August 2009 and were followed up at 1 (n=111), 3 (n=96), 6 (n=81), and 12 (n=52) months. All patients were treated with the Superion Interspinous Spacer. Main outcomes were back function with the Oswestry Disability Index (ODI), extremity and axial pain severity with an 11-point scale, health-related quality of life with the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the SF-36, and adverse events through 12 months. RESULTS: ODI improved 64% (p<0.001) through 12 months and clinical success was 92%. Extremity and axial pain improved 53% and 49% (both p<0.001), respectively, through 12 months with clinical success of 76% for axial pain and 86% for extremity pain. Health-related quality of life improved 41% for PCS and 22% for MCS (both p<0.001) through 12 months. PCS clinical success was 81% and MCS clinical success was 62% at 12 months. Four (5.9%) explants were performed although 3 were unrelated to the device. Eight procedure-related adverse events, observed in 6 (5.0%) patients, included superficial incision seroma (n=5), minor wound pain (n=2), and infection (n=1). CONCLUSIONS: Preliminary results with the Superion Interspinous Spacer suggest that it is an effective and safe treatment option for patients with moderate LSS who are unresponsive to conservative care. PMID- 22043256 TI - GM-CSF Fails to Improve Immune Responses to Booster Hepatitis B Vaccination in HIV-Infected Individuals. AB - BACKGROUND: Hepatitis B (HBV) vaccination is an important preventive intervention for HIV-infected population. Data regarding booster HBV vaccine for persons with low HBV surface antibody (sAb) titers after vaccination in this immunocompromised population is lacking. METHODS: We randomized 60 HIV-infected subjects lacking HBV protection after completion of 3 doses of HBV vaccine to receive a booster dose of HBV vaccine with 250mcg GM-CSF as an adjuvant or booster vaccine alone. RESULTS: GM-CSF was safe with expected side effects. However, only 35% of persons receiving GM-CSF developed protective sAb while 50% in vaccine only arm developed protection (P = 0.47). Overall, only 28% of subjects maintained protective sAb 1 year after vaccination. CONCLUSIONS: GM-CSF failed to improve responses to the booster HBV vaccination. Overall, response was poor with only 42% of persons responding at one month post-vaccination confirming booster vaccination with the current HBV vaccine has poor immunogenicity among HIV-infected persons. Further research is needed to develop optimal vaccination strategies in HIV-infected persons. PMID- 22043257 TI - Parasites induced skin allergy: a strategic manipulation of the host immunity. AB - The absence of a consistent link between parasitoses and skin allergic symptoms in the clinical investigations contrasts to the fact that some parasites are the most potent inducers of immunoglobulin E that exist in nature. To shed some light into this question, this review is focused on the actual knowledge regarding parasites life cycle, interactions with host immunity, the influence on host behavior, and finally the role of all these factors on the skin allergy. The collected data demonstrate that parasites could manipulate the host behavior for its own benefit in different ways, altering its (epi)genetic, biochemical, immunologic or physiologic functions as well as altering its behavior and activity. In this context, skin allergy may be associated with certain stages of the parasites' life cycle and migration into biological barriers, but not necessarily with presence of the parasitosis in the host organism. As compared to T helper (Th) 1 response, the Th2 one, the eosinophilic infiltration and the complement inhibition could assure better conditions for the development of some parasites. Taken together, the suggested hypotheses could be a plausible explanation for the epidemiological puzzle regarding urticaria occurrence, Th2 response and parasitoses, but further studies are necessary to provide better based conclusions. KEYWORDS: Eosinophilic Infiltration; Host behavior; Parasites life cycle; Skin allergy; Th1/Th2 response. PMID- 22043258 TI - Bilirubin as a Protective Factor for Rheumatoid Arthritis: An NHANES Study of 2003 - 2006 Data. AB - BACKGROUND: Rheumatoid arthritis(RA) is a chronic inflammatory, autoimmune polyarthritis, with a prevalence estimated at one percent of the United States(US) population. Serum bilirubin, because of its antioxidant nature, has been conjectured to exert an anti-inflammatory biologic effect. The objective of this study is to discern whether higher serum Total Bilirubin(TBili) levels are protective against RA. METHODS: This is a secondary analysis of National Health and Nutrition Examination Survey (NHANES) data collected between 2003-2006. Study participants completed a comprehensive questionnaire regarding their health history, underwent a physical examination, and had body fluids collected for laboratory studies. In NHANES, to assess for the presence of RA, the following questions were asked: Doctor ever said you had arthritis?" If so, Which type of arthritis. Statistical analysis was performed, using SAS version 9.1, proc survey methods. Participant data were adjusted for demographic characteristics as well as risk factors for RA. RESULTS: NHANES 2003-2006 included 20,470 individuals, chosen as a representative sampling of the entire US population. Exclusion criteria included age less than twenty years or liver dysfunction, defined as history of abnormal liver function tests or liver disease. 8,147 subjects did not have any exclusion criteria and were included in the data analysis. RA is inversely related to the serum level of TBili with an odds ratio of 0.679 (95% CI 0.533-0.865) and remained significant even after adjusting for age, gender, race, education, and tobacco history, with an odds ratio 0.749 (95% CI 0.575 - 0.976). CONCLUSIONS: Our study supports the hypothesis that higher TBili levels are protective against RA. A plausible mechanism for this association would be that the anti-oxidant effects of TBili exert a physiologic anti-inflammatory effect, which provides protection against RA. This explanation is supported by prior studies which show that higher TBili levels are protective against stroke, atherosclerosis, and vasculitis. Further studies are needed to delineate the exact nature of the protective properties of TBili. KEYWORDS: Bilirubin; Rheumatoid arthritis; Antioxidant; Protective. PMID- 22043259 TI - A Comparison Between the StaRRsed Auto-Compact Erythrocyte Sedimentation Rate Instrument and the Westergren Method. AB - BACKGROUND: The Westergren method is the golden standard for measuring erythrocyte sedimentation rate (ESR). All ESR methods should agree with the standardized method of the International Council for Standardization in Hematology (ICSH). Citrate samples are commonly used for ESR. This extra sample adds costs and can be inconvenient for the patient. Therefore, some new automated ESR analyzers use EDTA samples, which are available for other hematology measurements. METHODS: We compared ESR measurements with StaRRsed Auto-Compact instrument to the ICSH standardized Westergren method in 200 patient samples. RESULTS: The correlation between methods was fairly good (R(2) = 0.72, y = 1.066x 0.24). However, with ESR results over 11 mm/h there were 55 subjects with a difference of over 30% between methods. CONCLUSIONS: This may have led to different treatment suggestions in 25 cases according to age- and gender dependent normal values. The difference may be caused by two different anticoagulants used, different measuring times and the correlation equation used. The StaRRsed ESR method should be in better agreement with the Westergren method, which is the golden standard. ESR results have notable impact on patient diagnosis and follow-up. KEYWORDS: ESR; Erythrocyte sedimentation rate; StaRRsed; Westergren method. PMID- 22043260 TI - Antioxidant Vitamins and Lipoperoxidation in Non-pregnant, Pregnant, and Gestational Diabetic Women: Erythrocytes Osmotic Fragility Profiles. AB - BACKGROUND: Inconsistent reports are available in the literature regarding the oxidative status and antioxidant capacity during the pathogenesis of gestational diabetes. Present study was aimed to evaluate oxidative stress during the development of gestational diabetes and to evaluate antioxidant capability in non pregnant (control), pregnant and gestational diabetics. METHODS: The study consisted of non-pregnant, healthy pregnant and patients suffering from gestational diabetes mellitus (GDM). Each group consisted of 23 women. We compared their oxidative and anti-oxidative system in blood. Their blood malondialdehyde (MDA) and antioxidant vitamins (C, E, A) were determined and compared to evaluate the oxidative status and anti-oxidative capacity of these groups. We have also compared the osmotic fragility profiles of the erythrocytes of these groups. RESULTS: Plasma MDA content in pregnant was significantly higher compared to non-pregnant (p < 0.001, 67.5%) and even in gestational diabetics; its value was found significantly further elevated (p = 0.001, 13.8%) compared to healthy pregnant. There was significant decline (p < 0.001, 41.9%) in the level of vitamin C in pregnant as compared to non-pregnant. Although in GDM the decrease was significant (p = 0.025, 20.6%) but comparatively lesser when compared to healthy pregnant. Vitamin E showed the increase of 9.6% during pregnancy, although this alteration was non-significant (p = 0.09), but the level was found to decline significantly (p < 0.001, 25.5%) in GDM compared to pregnant group. Vitamin A contents were also decreased in pregnant (p = 0.002, 17.4%) compared to non-pregnant and in GDM (p = 0.012, 11.2%) compared to pregnant group. Osmotic fragility (O.F.) profiles showed insignificant (p = 0.325) enhanced mean erythrocyte fragility (MEF) in pregnant but this increase was significant (p = 0.003) in case of GDM. The O.F. profiles of pregnant and GDM erythrocytes got shifted to the right side of the control one. CONCLUSIONS: Our findings indicate highly enhanced lipid peroxidation and significant depletion in antioxidant capacity during the development of gestational diabetes, and these alterations are not the cause but the consequence of GDM. However, further studies are warranted to examine a wider range of biochemical parameters to evaluate the potential risks of oxidative damage in GDM. KEYWORDS: Gestational diabetes; Oxidative stress; Anti-oxidants; Vitamins C, E, A; Osmotic fragility; Non-pregnant; Pregnant; GDM. PMID- 22043261 TI - Meralgia paresthetica and femoral acetabular impingement: a possible association. AB - Meralgia paresthetica consists of pain and dysesthesia in the anterolateral thigh. Etiology is divided into spontaneous and iatrogenic causes. To my knowledge this has never been attributed to femoral acetabular impingement. This case highlights the presence of lateral femoral cutaneous neuropathy in the setting of femoral acetabular impingement syndrome thus raising the possibility of an association. KEYWORDS: Femoral acetabular impingement; Lateral femoral cutaneous nerve; Dysesthesia; Nerve conduction studies. PMID- 22043262 TI - Hematogenous long bone osteomyelitis by prevotella (bacteroides) melaninogenicus. AB - Anaerobic infections are difficult to recognize and may lead to life threatening complications. We present the case of an acute Prevotella hematogenous infection of the humerus in a previously healthy adult patient, treated with a two-stage surgical treatment, emphasizing on the importance of the radical surgical debridement and the selection of the appropriate antimicrobial agents. To our knowledge, such an acute hematogenous infection has not been previously reported in the literature. KEYWORDS: Osteomyelitis; Gram-negative hematogenous infections; Two stage surgical treatment. PMID- 22043263 TI - Intratesticular epidermoid cyst: a rare tumor. AB - Testicular epidermoid cyst is extremely rare injury, which in recent studies has been regarded as a tumor. Some authors consider this lesion as a cystic monodermal teratoma, the histogenesis remains controversial. In this study we provide clinical and morphological characteristics of an epidermoid cyst in the left testicle in a 16 years old patient, where apparently a nodular lesion in the left testicle was detected. KEYWORDS: Cyst; Epidermoid; Intratesticular. PMID- 22043264 TI - Case Review of Sarcoidosis Resembling Sjogren's Syndrome. AB - We would like to report a case of a 29-year-old male patient who presented with multiple lymphadenopathy and vague symptoms of low grade fever, cough, weight loss, rashes, vomiting, dry eyes and dry mouth. Physical examination revealed submandibular lymphadenopathy, vasculitic rashes over both lower limbs, and parotid gland enlargement. Blood investigations showed mild anemia with leukocytosis, predominantly eosinophilia and high erythrocyte sedimentation rate and C-reactive protein. Computed tomography of the neck, thorax and abdomen showed bilateral submandibular, submental adenopathy, mediastinal and para-aortic lymphadenopathy with generalized reticulonodular densities in both lower lobes. There were hepatomegaly and bilateral enlarged kidneys with renal cyst. Histopathological examination from the cervical lymph node later revealed non caseating granuloma, consistent of sarcoidosis. Patient responded well to prednisolone 50 mg daily with subsequent reduction in the size of cervical lymphadenopathy and parotid swelling. KEYWORDS: Lymphadenopathy; Granuloma; Sjogren; Sarcoidosis. PMID- 22043265 TI - The effects of physical activity on the epiphyseal growth plates: a review of the literature on normal physiology and clinical implications. AB - BACKGROUND: Children need physical activity and generally do this through the aspect of play. Active play in the form of organized sports can appear to be a concern for parents. Clinicians should have a general physiological background on the effects of exercise on developing epiphyseal growth plates of bone. The purpose of this review is to present an overview of the effects of physical activity on the developing epiphyseal growth plates of children. METHODS: A National Library of Medicine (Pubmed) search was initiated using the keywords and combinations of keywords "growth plate", "epiphyseal plate", "child", "exercise", and "physical activity." DISCUSSION: Bone is a dynamic tissue with a balance of osteoblast and osteoclast formation. The normal functioning of the epiphyseal growth plate is an important clinical aspect. Much of the physiology of the epiphyseal growth plate in response to exercise includes the important mechanical component. Growth hormone, insulin-like growth factor I, glucocorticoid, thyroid hormone, estrogen, androgen, vitamin D, and leptin are seen as key physiological factors. While there is a need for children to participate in physical activity, clinical consideration needs to be given to how the epiphyseal growth plate functions. CONCLUSIONS: Mechanical loading of the bone is important for epiphyseal plate physiology. Exercise has a healthy function on the normal growth of this important biomechanical feature. Clinically, over-exertion in the form of increased load bearing on the epiphyseal growth plate creates an ideal injury. There is a paucity of research on inactivity on the epiphyseal growth plate resulting in stress deprivation. Further research should take into consideration what lack of exercise and lessened mechanical load bearing has on the function of the epiphyseal growth plate. KEYWORDS: Child; Physical activity; Epiphyseal growth plates; Bone; Exercise; Mechanical loading. PMID- 22043266 TI - Research on the performance of the spastic calf muscle of young adults with cerebral palsy. AB - BACKGROUND: The aim of this study was to find an objective graduation of pes equinus in infantile cerebral palsy, especially with regard to functional aspects, to allow a differentiated choice of the therapeutic options. Very often raises the question of whether a surgical lengthening of the Achilles tendon may let expect a functional improvement. METHODS: For this documentation 17 patients with pes equinus and a diagnosis of spastic cerebral palsy, primarily of the lower limbs, and hemiplegia were examined first clinically and then by a procedure for calculating the functional kinetic parameters from an in-shoe plantar pressure distribution measurement (novel pedar-X system), which is used in many orthopedic practices and clinics as a standard measuring device. Using additional video motion analysis, the flexion in the ankle joint and the ankle joint torque were determined. From this the physical performance of the spastically shortened calf muscle was calculated. The course of the curves of torque and joint performance allows a functional classification of the pes equinus. RESULTS: Approximately three quarters of all pes equinus demonstrated functional activity of the most part of the normal push-off propulsion power. Even the rigid pes equinus was capable of performing push-off propulsion work, provided it converted energy that was absorbed during the heel-strike phase and released it again during the push-off phase. This suggests that the function of paretic ankle joint is better than its kinematics of motion. CONCLUSIONS: A heel strike with a pes equinus triggers via stretching stimuli in the muscle-ligament structure reflex motor functions, thereby causing the typical spastic gait pattern. This remarkable gait pattern is often evaluated as dysfunctional and as absolutely requiring correction. However, an aspect possibly neglected in this instance is the fact that this gait pattern may be efficient for the patient and may in fact be a suitable means allowing for economic locomotion despite the cerebral control deficits. KEYWORDS: Pes equinus; Cerebral palsy; Pedography; Ankle joint performance. PMID- 22043267 TI - From Clinical Presentation to the Outcome: the Natural History of PML in a Portuguese Population of HIV Infected Patients. AB - BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system, associated with immunosuppression states. As there are only some non-published documents concerning PML in HIV infected patients in Portugal, we pretend to characterize natural history of PML infection in a population of HIV patients. METHODS: We retrospectively reviewed, from 1992 to 2009, PML cases in a population of 724 HIV infected patients followed in our institution. Clinical, biological, imagery features and outcomes were characterized. RESULTS: Twenty-five (3.45%) patients were identified as having PML. The mean time between HIV and PML diagnosis was 20.4 months. PML was the presentation of HIV infection in 40% of the patients, and 92% had CD4 T cell count lower than 200/mm(3). Paresis was the most common clinical presentation. No specific characteristics were found in cerebrospinal fluid and JCV DNA was positive in 3 of 7 patients. MRI revealed characteristic findings. Combined antiretroviral therapy was started or changed in 96% of the patients. Neurological condition got worse in 12 patients. From the 14 deaths, 5 were directly attributed to PML progression. Follow-up was lost in 8 patients. CONCLUSIONS: PML was the presentation of HIV infection in more than 1/3 of patients, frequently associated with advanced immunocompromise. MRI sensitivity to PML is high, and JCV DNA determination in CSF was not revealed to be sensible. PML diagnosis should be taken into account in HIV patients presenting any neurological symptoms, and HIV infection should be suspected when radiological findings suggest PML lesions even in previously healthy individuals. KEYWORDS: Progressive multifocal leukoencephalopathy; JC virus; Human immunodeficiency virus; Demyelinating disease. PMID- 22043268 TI - Nausea and vomiting as the reasons for encounter in general practice. AB - BACKGROUND: The present study aimed to explore the consultation prevalence, differential diagnoses, and management of patients presenting with nausea or vomiting to their family doctors. METHODS: Cross-sectional data were collected from randomly selected patients during the SESAM 2 study (October 1, 1999 to September 30, 2000). We contacted 2510 doctors; 270 (10.8%) of them participated in the study. Data were collected from randomly selected patients previously known to the general practitioner. Unpublished but publicly available data from the Dutch Transition Project were also analysed. RESULTS: One hundred and sixty nine of the total 8874 patients consulted their general practitioner for nausea/vomiting; 97 (57.4%) were female and 72 (42.6%) were male. Most patients suffering from nausea or vomiting in general practice were aged between 15 and 64 years. Nearly all patients were given a physical examination. Most diagnoses were made without further investigation, additional diagnostic procedures were found to be necessary in only 7 patients. Drugs were prescribed as the most frequent form of medical treatment, in 76.3% of cases. Non-infectious gastroenteritis or colitis was the most frequent diagnosis. Nausea or vomiting was associated with diarrhoea, fever, and abdominal pain. Headache, general weakness, and epigastric pain were also statistically significantly associated with nausea or vomiting. CONCLUSIONS: Many disorders cause nausea or vomiting. Although most of the patients were diagnosed with non-infectious gastroenteritis or colitis, the general practitioner also has to bear in mind that nausea and vomiting may be alarm symptoms. Medication was prescribed in most of the cases and there were only a few referrals to a specialist or hospital. Life-threatening disorders (appendicitis, bowel obstruction/ileus) were found in a few cases presenting with nausea or vomiting. KEYWORDS: Nausea; Vomiting; General practice; Primary care. PMID- 22043269 TI - Early Maternal Serum beta-human Chorionic Gonadotropin Measurements After ICSI in the Prediction of Long-term Pregnancy Outcomes: A Retrospective Cohort Analysis. AB - BACKGROUND: Initial low maternal serum beta-human chorionic gonadotropin (beta hCG) is a good predictor of early pregnancy demise. Our objective was to determine its predictive value in determining the long-term outcome in ICSI pregnancies. METHODS: A retrospective cohort study was designed at the Saudi Center for Assisted Reproduction. Two hundred and sixty-one women with ICSI pregnancies were followed up from initial beta-hCG level determination till the end of pregnancy. Accuracy of early beta-hCG in predicting the occurrence of a live-birth, ongoing pregnancy, late miscarriage, ectopic pregnancy and early miscarriage following ICSI was measured. RESULTS: beta-hCG levels were significantly different in pregnancies that reached the stage of an ongoing pregnancy and live-birth as compared to early pregnancy loss. The ROC curves demonstrated a high sensitivity for identifying patients with ectopic pregnancies and early miscarriage (100% and 93.33% respectively). The remaining results ranged from a sensitivity of 69% to 79% and specificity of 62% to 75%. CONCLUSIONS: In ICSI pregnancies, a single early beta-hCG may help to identify pregnancies that will reach full-term and delivery. KEYWORDS: ICSI; Human chorionic gonadotropin; Outcome; Pregnancy. PMID- 22043270 TI - Effect of skin-to-skin contact on preterm infant skin barrier function and hospital-acquired infection. AB - BACKGROUND: The preterm infants' skin is structurally and functionally immature at birth because of immature stratum corneum barrier function, leading to problems with fluid loses, thermoregulation, and infection. Two parameters of barrier function can be non-invasively assessed: Stratum Corneum Hydration (SCH) and Transepidermal Water Loss (TEWL). Skin-to-Skin Care (SSC) is the proposed independent variable that might affect barrier function by decreasing TEWL and increasing SCH, thereby improving stratum corneum barrier function and consequently decreasing the rate of infection. No study of SSC's effects on TEWL and SCH of preterm infants could be found. The purpose of the study was to determine the effect of 5 daily Skin-to-Skin Contact sessions on infant skin hydration (SCH), transepidermal evaporated water loss (TEWL), and on SCH when TEWL was controlled, and on the presence of hospital acquired infection. METHODS: A one-group pretest-test-posttest design with 10 preterm infants (28 - 30 wks GA < 32 wks postmenstrual age, and no infection at entry). Test = 90 minutes of SSC; pre-test and post-test = 30 minutes each of prone positioning in an incubator. SCH and TEWL were taken on Days 1 and 5 at the beginning, middle and end of each period using Multi-Probe Adaptor. A 3 X 3 X 2 Repeated Measures Mixed Models Design, including a covariate, was used to analyze level of Skin Hydration. Specifically, the model tested comparisons in SCH made across repetitions, time, and days, as well as all possible interactions while controlling for TEWL. Descriptive statistics described the number of positive blood cultures during hospitalization and the presence of infections four weeks post-discharge. RESULTS: Significant differences in skin hydration were found across TIME (Pre SSC, SSC, Post-SSC) (F = 21.86; p < 0.001). One infant had a positive blood culture during hospitalization; no infants had signs of infection by 4 weeks post discharge. CONCLUSIONS: The study has begun fulfilling the recommendation that SSC be tested as a strategy to improve skin hydration, but reveals that evaporative loss may be higher during SSC than during incubator care, and that the higher transepidermal evaporated water loss values may not necessarily be detrimental because few infections occurred even in its presence. A definitive randomized controlled trial is recommended. KEYWORDS: Skin-to-skin contact; Skin hydration; Transepidermal water loss; Infection; Preterm. PMID- 22043271 TI - Talactoferrin immunotherapy in metastatic renal cell carcinoma: a case series of four long-term survivors. AB - Talactoferrin alfa (also known as recombinant human lactoferrin, rhLF) is a novel immunomodulatory protein that has previously demonstrated anti-tumor properties in animal models. Following a successful phase I trial, it was administered orally to patients with metastatic renal cell carcinoma (RCC) in a phase II trial conducted at the Michael E. DeBakey Veterans Affairs Medical Center in Houston, Texas, among other sites. We report a case series of 4 patients treated at our institution with very encouraging progression-free survivals, all exceeding 30 months, in order to suggest that this agent merits further study. These four patients with radiographically progressive metastatic RCC received single-agent oral talactoferrin in daily doses of 9 grams, given in cycles of 2 weeks on/2 weeks off, until evidence of toxicity or disease progression. Given the small sample size and the heterogenous tumor biology of RCC, tumor growth rate was used as a primary endpoint so that each patient could serve as their own control. The agent's effectiveness was then determined through radiographic tracking of the tumors before, during, and after treatment, with use of the Response Evaluation Criteria in Solid Tumors (RECIST) protocol to follow target lesions. The results showed that the drug was well tolerated, with no occurrence of talactoferrin related grade 3 or 4 adverse events or laboratory anomalies by NCI-CTEP criteria. The four patients described in the case series demonstrated very encouraging progression-free survivals, all exceeding 30 months. We conclude that decreased tumor growth rate may correlate with increased progression-free survival. Talactoferrin is a promising, well-tolerated agent whose clinical benefits should be evaluated in a randomized phase III study with a placebo control arm. KEYWORDS: Talactoferrin; Immunotherapy; Renal cell carcinoma; Metastatic. PMID- 22043272 TI - Primary hydatid cyst: an unusual cause of a mass in the supraclavicular region of the neck. AB - Hydatid disease, also known as echinococcosis or hydatidosis, is an infectious disease caused by the cestode Echinococcus. Echinococcus granulosus is the most common Echinococcus species affecting human beings. It may affect any organ and tissue in the body, in particular the liver and lung. Musculoskeletal or soft tissue hydatidosis accounts for about 0.5% 5% of all echinococcal infections in endemic areas, and is almost always secondary to the hepatic or pulmonary disease. Even in regions where echinococcosis is endemic, hydatidosis of cervicofacial region is extremely rare. Herein, we present exceptionally rare case with an unusual localization of primary hydatid cyst in the left supraclavicular region of the neck. KEYWORDS: Hydatid cyst; Supraclavicular region; Neck; Unusual localization. PMID- 22043273 TI - Traumatic optic neuropathy and central retinal artery occlusion following blunt ocular trauma. AB - We present a case as a rare sign of traumatic optic neuropathy and central retinal artery occlusion following blunt ocular trauma. A 10-year-old child suffered complete loss of the vision of one eye following a blunt ocular injury. He sustained an occlusion of the central retinal artery and traumatic optic neurupathy of the affected eye. Isolated cases of central retinal vessel occlusions and traumatic optic neurapathy following ocular blunt trauma are rare conditions. Clinicians to be aware of the potential for blunt ocular trauma to cause optic nerve damage and retinal vessel occlusions. KEYWORDS: Blunt ocular trauma; Retinal artery occlusion; Traumatic optic neuropathy. PMID- 22043274 TI - Meibum lipid composition in Asians with dry eye disease. AB - BACKGROUND: Previous lipidomic analyses of the human meibum had largely focused on individuals from non-Asian populations, despite the higher prevalence of dysfunctional tear syndrome (DTS) observed across Asia. Information pertaining to the alterations in lipid profiles in relation to DTS onset and progression is also lacking and warrants comprehensive experimental analysis. METHODOLOGIES/PRINCIPAL FINDINGS: We examined the meibum lipidome of 27 DTS patients and 10 control subjects for a total of 256 lipid species from 12 major lipid classes, including cholesteryl ester (CE), wax ester (WE), triacylglyceride (TAG), (O-acyl)-omega-hydroxy fatty acid (OAHFA), glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG) and sphingolipids (sphingomyelin, SM; ceramide, Cer; glucosylceramide, GluCer; dihexosylceramide, DihexCer). Neutral lipids were analysed using high-performance liquid-chromatography coupled with mass spectrometry (HPLC/MS) and tandem mass spectrometry (MS/MS) was used for the qualitative and quantitative analysis of polar lipid species. DTS patients were classified into three severity groups (i.e. mild, moderate and severe) based on the ocular surface disease index (OSDI). A significantly lower level of TAG (p<0.05) was observed in patients under the moderate category compared to the mild category. Notably, a number of OAHFA species displayed consistently decreasing levels that correlate with increasing disease severity. An attempt was also made to investigate the changes in meibum lipid profiles of DTS patients compared to normal individuals classified based on OSDI score. Several unsaturated TAG and PC species were found at significantly higher levels (p<0.05) in patients than controls. CONCLUSION: The current study presents, for the first time, a comprehensive lipidome of meibum from individuals of an Asian ethnicity, which can potentially offer new insights into the higher prevalence of DTS observed amongst Asian populations. This study also represents an attempt towards identification of lipid species in meibum which could serve as marker for DTS. PMID- 22043275 TI - Evaluating the combined effectiveness of influenza control strategies and human preventive behavior. AB - Control strategies enforced by health agencies are a major type of practice to contain influenza outbreaks. Another type of practice is the voluntary preventive behavior of individuals, such as receiving vaccination, taking antiviral drugs, and wearing face masks. These two types of practices take effects concurrently in influenza containment, but little attention has been paid to their combined effectiveness. This article estimates this combined effectiveness using established simulation models in the urbanized area of Buffalo, NY, USA. Three control strategies are investigated, including: Targeted Antiviral Prophylaxis (TAP), workplace/school closure, community travel restriction, as well as the combination of the three. All control strategies are simulated with and without regard to individual preventive behavior, and the resulting effectiveness are compared. The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. The preventive behavior of individuals could save medical resources for control strategies and avoid unnecessary socio-economic interruptions. This research adds a human behavioral dimension into the simulation of control strategies and offers new insights into disease containment. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment. PMID- 22043276 TI - Amplification of P. falciparum Cytoadherence through induction of a pro-adhesive state in host endothelium. AB - This study examined the ability of P.falciparum-infected erythrocytes (IE) to induce a pro-adhesive environment in the host endothelium during malaria infection, prior to the systemic cytokine activation seen in the later phase of disease. Previous work had shown increases in receptor levels but had not measured to actual impact on IE binding. Using a co-culture system with a range of endothelial cells (EC) and IE with different cytoadherent properties, we have characterised the specific expression of adhesion receptors and subsequent IE binding by FACS and adhesion assays. We have also examined the specific signalling pathways induced during co-culture that are potentially involved in the induction of receptor expression. The results confirmed that ICAM-1 is up regulated, albeit at much lower levels than seen with TNF activation, in response to co-culture with infected erythrocytes in all three tissue endothelial cell types tested but that up-regulation of VCAM-1 is tissue-dependent. This small increase in the levels of EC receptors correlated with large changes in IE adhesion ability. Co-culture with either RBC or IE increased the potential of subsequent adhesion indicating priming/modulation effects on EC which make them more susceptible to adhesion and thereby the recruitment of IE. Trypsin surface digestion of IE and the use of a Pfsbp1-knockout (ko) parasite line abrogated the up-regulation of ICAM-1 and reduced IE binding to EC suggesting that PfEMP-1 and other molecules exported to the IE surface via the PfSBP1 pathway are major mediators of this phenotype. This was also supported by the higher induction of EC adhesion receptors by adherent IE compared to isogenic, non-adherent lines. PMID- 22043277 TI - Importance of correlation between gene expression levels: application to the type I interferon signature in rheumatoid arthritis. AB - BACKGROUND: The analysis of gene expression data shows that many genes display similarity in their expression profiles suggesting some co-regulation. Here, we investigated the co-expression patterns in gene expression data and proposed a correlation-based research method to stratify individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using blood from rheumatoid arthritis (RA) patients, we investigated the gene expression profiles from whole blood using Affymetrix microarray technology. Co-expressed genes were analyzed by a biclustering method, followed by gene ontology analysis of the relevant biclusters. Taking the type I interferon (IFN) pathway as an example, a classification algorithm was developed from the 102 RA patients and extended to 10 systemic lupus erythematosus (SLE) patients and 100 healthy volunteers to further characterize individuals. We developed a correlation-based algorithm referred to as Classification Algorithm Based on a Biological Signature (CABS), an alternative to other approaches focused specifically on the expression levels. This algorithm applied to the expression of 35 IFN-related genes showed that the IFN signature presented a heterogeneous expression between RA, SLE and healthy controls which could reflect the level of global IFN signature activation. Moreover, the monitoring of the IFN related genes during the anti-TNF treatment identified changes in type I IFN gene activity induced in RA patients. CONCLUSIONS: In conclusion, we have proposed an original method to analyze genes sharing an expression pattern and a biological function showing that the activation levels of a biological signature could be characterized by its overall state of correlation. PMID- 22043278 TI - Brainstem and spinal cord circuitry regulating REM sleep and muscle atonia. AB - BACKGROUND: Previous work has suggested, but not demonstrated directly, a critical role for both glutamatergic and GABAergic neurons of the pontine tegmentum in the regulation of rapid eye movement (REM) sleep. METHODOLOGY/PRINCIPAL FINDINGS: To determine the in vivo roles of these fast acting neurotransmitters in putative REM pontine circuits, we injected an adeno associated viral vector expressing Cre recombinase (AAV-Cre) into mice harboring lox-P modified alleles of either the vesicular glutamate transporter 2 (VGLUT2) or vesicular GABA-glycine transporter (VGAT) genes. Our results show that glutamatergic neurons of the sublaterodorsal nucleus (SLD) and glycinergic/GABAergic interneurons of the spinal ventral horn contribute to REM atonia, whereas a separate population of glutamatergic neurons in the caudal laterodorsal tegmental nucleus (cLDT) and SLD are important for REM sleep generation. Our results further suggest that presynaptic GABA release in the cLDT SLD, ventrolateral periaqueductal gray matter (vlPAG) and lateral pontine tegmentum (LPT) are not critically involved in REM sleep control. CONCLUSIONS/SIGNIFICANCE: These findings reveal the critical and divergent in vivo role of pontine glutamate and spinal cord GABA/glycine in the regulation of REM sleep and atonia and suggest a possible etiological basis for REM sleep behavior disorder (RBD). PMID- 22043279 TI - No adverse effect of genetically modified antifungal wheat on decomposition dynamics and the soil fauna community--a field study. AB - The cultivation of genetically modified (GM) plants has raised several environmental concerns. One of these concerns regards non-target soil fauna organisms, which play an important role in the decomposition of organic matter and hence are largely exposed to GM plant residues. Soil fauna may be directly affected by transgene products or indirectly by pleiotropic effects such as a modified plant metabolism. Thus, ecosystem services and functioning might be affected negatively. In a litterbag experiment in the field we analysed the decomposition process and the soil fauna community involved. Therefore, we used four experimental GM wheat varieties, two with a race-specific antifungal resistance against powdery mildew (Pm3b) and two with an unspecific antifungal resistance based on the expression of chitinase and glucanase. We compared them with two non-GM isolines and six conventional cereal varieties. To elucidate the mechanisms that cause differences in plant decomposition, structural plant components (i.e. C?N ratio, lignin, cellulose, hemicellulose) were examined and soil properties, temperature and precipitation were monitored. The most frequent taxa extracted from decaying plant material were mites (Cryptostigmata, Gamasina and Uropodina), springtails (Isotomidae), annelids (Enchytraeidae) and Diptera (Cecidomyiidae larvae). Despite a single significant transgenic/month interaction for Cecidomyiidae larvae, which is probably random, we detected no impact of the GM wheat on the soil fauna community. However, soil fauna differences among conventional cereal varieties were more pronounced than between GM and non-GM wheat. While leaf residue decomposition in GM and non-GM wheat was similar, differences among conventional cereals were evident. Furthermore, sampling date and location were found to greatly influence soil fauna community and decomposition processes. The results give no indication of ecologically relevant adverse effects of antifungal GM wheat on the composition and the activity of the soil fauna community. PMID- 22043280 TI - BID-F1 and BID-F2 domains of Bartonella henselae effector protein BepF trigger together with BepC the formation of invasome structures. AB - The gram-negative, zoonotic pathogen Bartonella henselae (Bhe) translocates seven distinct Bartonella effector proteins (Beps) via the VirB/VirD4 type IV secretion system (T4SS) into human cells, thereby interfering with host cell signaling [1], [2]. In particular, the effector protein BepG alone or the combination of effector proteins BepC and BepF trigger massive F-actin rearrangements that lead to the establishment of invasome structures eventually resulting in the internalization of entire Bhe aggregates [2], [3]. In this report, we investigate the molecular function of the effector protein BepF in the eukaryotic host cell. We show that the N-terminal [E/T]PLYAT tyrosine phosphorylation motifs of BepF get phosphorylated upon translocation but do not contribute to invasome-mediated Bhe uptake. In contrast, we found that two of the three BID domains of BepF are capable to trigger invasome formation together with BepC, while a mutation of the WxxxE motif of the BID-F1 domain inhibited its ability to contribute to the formation of invasome structures. Next, we show that BepF function during invasome formation can be replaced by the over-expression of constitutive-active Rho GTPases Rac1 or Cdc42. Finally we demonstrate that BID-F1 and BID-F2 domains promote the formation of filopodia-like extensions in NIH 3T3 and HeLa cells as well as membrane protrusions in HeLa cells, suggesting a role for BepF in Rac1 and Cdc42 activation during the process of invasome formation. PMID- 22043281 TI - Increased cardiovascular reactivity to acute stress and salt-loading in adult male offspring of fat fed non-obese rats. AB - Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Delta systolic blood pressure (SBP) and Deltaheart rate (HR)) with a prolonged recovery time compared to male OC. alpha1/beta-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli. PMID- 22043282 TI - Cellulosomics, a gene-centric approach to investigating the intraspecific diversity and adaptation of Ruminococcus flavefaciens within the rumen. AB - BACKGROUND: The bovine rumen maintains a diverse microbial community that serves to break down indigestible plant substrates. However, those bacteria specifically adapted to degrade cellulose, the major structural component of plant biomass, represent a fraction of the rumen microbiome. Previously, we proposed scaC as a candidate for phylotyping Ruminococcus flavefaciens, one of three major cellulolytic bacterial species isolated from the rumen. In the present report we examine the dynamics and diversity of scaC-types both within and between cattle temporally, following a dietary switch from corn-silage to grass-legume hay. These results were placed in the context of the overall bacterial population dynamics measured using the 16S rRNA. PRINCIPAL FINDINGS: As many as 117 scaC types were estimated, although just nineteen were detected in each of three rumens tested, and these collectively accounted for the majority of all types present. Variation in scaC populations was observed between cattle, between planktonic and fiber-associated fractions and temporally over the six-week survey, and appeared related to scaC phylogeny. However, by the sixth week no significant separation of scaC populations was seen between animals, suggesting enrichment of a constrained set of scaC-types. Comparing the amino-acid translation of each scaC-type revealed sequence variation within part of the predicted dockerin module but strong conservation in the N-terminus, where the cohesin module is located. CONCLUSIONS: The R. flavefaciens species comprises a multiplicity of scaC-types in-vivo. Enrichment of particular scaC-types temporally, following a dietary switch, and between fractions along with the phylogenetic congruence suggests that functional differences exist between types. Observed differences in dockerin modules suggest at least part of the functional heterogeneity may be conferred by scaC. The polymorphic nature of scaC enables the relative distribution of R. flavefaciens strains to be examined and represents a gene-centric approach to investigating the intraspecific adaptation of an important specialist population. PMID- 22043283 TI - Dissociation of progressive dopaminergic neuronal death and behavioral impairments by Bax deletion in a mouse model of Parkinson's diseases. AB - Parkinson's disease (PD) is a common, late-onset movement disorder with selective degeneration of dopaminergic (DA) neurons in the substantia nigra (SN). Although the neurotoxin 6-hydroxydopamine (6-OHDA) has been used to induce progressive degeneration of DA neurons in various animal models of PD, the precise molecular pathway and the impact of anti-apoptotic treatment on this neurodegeneration are less understood. Following a striatal injection of 6-OHDA, we observed atrophy and progressive death of DA neurons in wild-type mice. These degenerating DA neurons never exhibited signs of apoptosis (i.e., caspase-3 activation and cytoplasmic release of cytochrome C), but rather show nuclear translocation of apoptosis-inducing factor (AIF), a hallmark of regulated necrosis. However, mice with genetic deletion of the proapoptotic gene Bax (Bax-KO) exhibited a complete absence of 6-OHDA-induced DA neuron death and nuclear translocation of AIF, indicating that 6-OHDA-induced DA neuronal death is mediated by Bax-dependent AIF activation. On the other hand, DA neurons that survived in Bax-KO mice exhibited marked neuronal atrophy, without significant improvement of PD-related behavioral deficits. These findings suggest that anti-apoptotic therapy may not be sufficient for PD treatment, and the prevention of Bax-independent neuronal atrophy may be an important therapeutic target. PMID- 22043284 TI - Spontaneous hemodynamic oscillations during human sleep and sleep stage transitions characterized with near-infrared spectroscopy. AB - Understanding the interaction between the nervous system and cerebral vasculature is fundamental to forming a complete picture of the neurophysiology of sleep and its role in maintaining physiological homeostasis. However, the intrinsic hemodynamics of slow-wave sleep (SWS) are still poorly known. We carried out 30 all-night sleep measurements with combined near-infrared spectroscopy (NIRS) and polysomnography to investigate spontaneous hemodynamic behavior in SWS compared to light (LS) and rapid-eye-movement sleep (REM). In particular, we concentrated on slow oscillations (3-150 mHz) in oxy- and deoxyhemoglobin concentrations, heart rate, arterial oxygen saturation, and the pulsation amplitude of the photoplethysmographic signal. We also analyzed the behavior of these variables during sleep stage transitions. The results indicate that slow spontaneous cortical and systemic hemodynamic activity is reduced in SWS compared to LS, REM, and wakefulness. This behavior may be explained by neuronal synchronization observed in electrophysiological studies of SWS and a reduction in autonomic nervous system activity. Also, sleep stage transitions are asymmetric, so that the SWS-to-LS and LS-to-REM transitions, which are associated with an increase in the complexity of cortical electrophysiological activity, are characterized by more dramatic hemodynamic changes than the opposite transitions. Thus, it appears that while the onset of SWS and termination of REM occur only as gradual processes over time, the termination of SWS and onset of REM may be triggered more abruptly by a particular physiological event or condition. The results suggest that scalp hemodynamic changes should be considered alongside cortical hemodynamic changes in NIRS sleep studies to assess the interaction between the autonomic and central nervous systems. PMID- 22043285 TI - Liquid facets-related (lqfR) is required for egg chamber morphogenesis during Drosophila oogenesis. AB - Clathrin interactor 1 [CLINT1] (also called enthoprotin/EpsinR) is an Epsin N terminal homology (ENTH) domain-containing adaptor protein that functions in anterograde and retrograde clathrin-mediated trafficking between the trans-Golgi network and the endosome. Removal of both Saccharomyces cerevisiae homologs, Ent3p and Ent5p, result in yeast that are viable, but that display a cold sensitive growth phenotype and mistrafficking of various vacuolar proteins. Similarly, either knock-down or overexpression of vertebrate CLINT1 in cell culture causes mistrafficking of proteins. Here, we have characterized Drosophila CLINT1, liquid-facets Related (lqfR). LqfR is ubiquitously expressed throughout development and is localized to the Golgi and endosome. Strong hypomorphic mutants generated by imprecise P-element excision exhibit extra macrochaetae, rough eyes and are female sterile. Although essentially no eggs are laid, the ovaries do contain late-stage egg chambers that exhibit abnormal morphology. Germline clones reveal that LqfR expression in the somatic follicle cells is sufficient to rescue the oogenesis defects. Clones of mutant lqfR follicle cells have a decreased cell size consistent with a downregulation of Akt1. We find that while total Akt1 levels are increased there is also a significant decrease in activated phosphorylated Akt1. Taken together, these results show that LqfR function is required to regulate follicle cell size and signaling during Drosophila oogenesis. PMID- 22043286 TI - Chronic morphine alters the presynaptic protein profile: identification of novel molecular targets using proteomics and network analysis. AB - Opiates produce significant and persistent changes in synaptic transmission; knowledge of the proteins involved in these changes may help to understand the molecular mechanisms underlying opiate dependence. Using an integrated quantitative proteomics and systems biology approach, we explored changes in the presynaptic protein profile following a paradigm of chronic morphine administration that leads to the development of dependence. For this, we isolated presynaptic fractions from the striata of rats treated with saline or escalating doses of morphine, and analyzed the proteins in these fractions using differential isotopic labeling. We identified 30 proteins that were significantly altered by morphine and integrated them into a protein-protein interaction (PPI) network representing potential morphine-regulated protein complexes. Graph theory based analysis of this network revealed clusters of densely connected and functionally related morphine-regulated clusters of proteins. One of the clusters contained molecular chaperones thought to be involved in regulation of neurotransmission. Within this cluster, cysteine-string protein (CSP) and the heat shock protein Hsc70 were downregulated by morphine. Interestingly, Hsp90, a heat shock protein that normally interacts with CSP and Hsc70, was upregulated by morphine. Moreover, treatment with the selective Hsp90 inhibitor, geldanamycin, decreased the somatic signs of naloxone-precipitated morphine withdrawal, suggesting that Hsp90 upregulation at the presynapse plays a role in the expression of morphine dependence. Thus, integration of proteomics, network analysis, and behavioral studies has provided a greater understanding of morphine induced alterations in synaptic composition, and identified a potential novel therapeutic target for opiate dependence. PMID- 22043287 TI - Functional analysis of the magnetosome island in Magnetospirillum gryphiswaldense: the mamAB operon is sufficient for magnetite biomineralization. AB - Bacterial magnetosomes are membrane-enveloped, nanometer-sized crystals of magnetite, which serve for magnetotactic navigation. All genes implicated in the synthesis of these organelles are located in a conserved genomic magnetosome island (MAI). We performed a comprehensive bioinformatic, proteomic and genetic analysis of the MAI in Magnetospirillum gryphiswaldense. By the construction of large deletion mutants we demonstrate that the entire region is dispensable for growth, and the majority of MAI genes have no detectable function in magnetosome formation and could be eliminated without any effect. Only <25% of the region comprising four major operons could be associated with magnetite biomineralization, which correlated with high expression of these genes and their conservation among magnetotactic bacteria. Whereas only deletion of the mamAB operon resulted in the complete loss of magnetic particles, deletion of the conserved mms6, mamGFDC, and mamXY operons led to severe defects in morphology, size and organization of magnetite crystals. However, strains in which these operons were eliminated together retained the ability to synthesize small irregular crystallites, and weakly aligned in magnetic fields. This demonstrates that whereas the mamGFDC, mms6 and mamXY operons have crucial and partially overlapping functions for the formation of functional magnetosomes, the mamAB operon is the only region of the MAI, which is necessary and sufficient for magnetite biomineralization. Our data further reduce the known minimal gene set required for magnetosome formation and will be useful for future genome engineering approaches. PMID- 22043288 TI - Bioenergetic consequences of PINK1 mutations in Parkinson disease. AB - BACKGROUND: Mutations of the gene for PTEN-induced kinase 1 (PINK1) are a cause of familial Parkinson's disease (PD). PINK1 protein has been localised to mitochondria and PINK1 gene knockout models exhibit abnormal mitochondrial function. The purpose of this study was to determine whether cells derived from PD patients with a range of PINK1 mutations demonstrate similar defects of mitochondrial function, whether the nature and severity of the abnormalities vary between mutations and correlate with clinical features. METHODOLOGY: We investigated mitochondrial bioenergetics in live fibroblasts from PINK1 mutation patients using single cell techniques. We found that fibroblasts from PINK1 mutation patients had significant defects of bioenergetics including reduced mitochondrial membrane potential, altered redox state, a respiratory deficiency that was determined by substrate availability, and enhanced sensitivity to calcium stimulation and associated mitochondrial permeability pore opening. There was an increase in the basal rate of free radical production in the mutant cells. The pattern and severity of abnormality varied between different mutations, and the less severe defects in these cells were associated with later age of onset of PD. CONCLUSIONS: The results provide insight into the molecular pathology of PINK1 mutations in PD and also confirm the critical role of substrate availability in determining the biochemical phenotype--thereby offering the potential for novel therapeutic strategies to circumvent these abnormalities. PMID- 22043289 TI - Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study. AB - AIMS: Endogenous cardiac progenitor cells, expanded from explants via cardiosphere formation, present a promising cell source to prevent heart failure following myocardial infarction. Here we used cine-magnetic resonance imaging (MRI) to track administered cardiosphere-derived cells (CDCs) and to measure changes in cardiac function over four months in the infarcted rat heart. METHODS AND RESULTS: CDCs, cultured from neonatal rat heart, comprised a heterogeneous population including cells expressing the mesenchymal markers CD90 and CD105, the stem cell marker c-kit and the pluripotency markers Sox2, Oct3/4 and Klf-4. CDCs (2 * 10(6)) expressing green fluorescent protein (GFP+) were labelled with fluorescent micron-sized particles of iron oxide (MPIO). Labelled cells were administered to the infarcted rat hearts (n = 7) by intramyocardial injection immediately following reperfusion, then by systemic infusion (4 * 10(6)) 2 days later. A control group (n = 7) was administered cell medium. MR hypointensities caused by the MPIOs were detected at all times and GFP+ cells containing MPIO particles were identified in tissue slices at 16 weeks. At two days after infarction, cardiac function was similar between groups. By 6 weeks, ejection fractions in control hearts had significantly decreased (47 +/- 2%), but this was not evident in CDC-treated hearts (56 +/- 3%). The significantly higher ejection fractions in the CDC-treated group were maintained for a further 10 weeks. In addition, CDC-treated rat hearts had significantly increased capillary density in the peri-infarct region and lower infarct sizes. MPIO-labelled cells also expressed cardiac troponin I, von Willebrand factor and smooth muscle actin, suggesting their differentiation along the cardiomyocyte lineage and the formation of new blood vessels. CONCLUSIONS: CDCs were retained in the infarcted rat heart for 16 weeks and improved cardiac function. PMID- 22043290 TI - The simian immunodeficiency virus targets central cell cycle functions through transcriptional repression in vivo. AB - A massive and selective loss of CD4+ memory T cells occurs during the acute phase of immunodeficiency virus infections. The mechanism of this depletion is poorly understood but constitutes a key event with implications for progression. We assessed gene expression of purified T cells in Rhesus Macaques during acute SIVmac239 infection in order to define mechanisms of pathogenesis. We observe a general transcriptional program of over 1,600 interferon-stimulated genes induced in all T cells by the infection. Furthermore, we identify 113 transcriptional changes that are specific to virally infected cells. A striking downregulation of several key cell cycle regulator genes was observed and shared promotor-region E2F binding sites in downregulated genes suggested a targeted transcriptional control of an E2F regulated cell cycle program. In addition, the upregulation of the gene for the fundamental regulator of RNA polymerase II, TAF7, demonstrates that viral interference with the cell cycle and transcriptional regulation programs may be critical components during the establishment of a pathogenic infection in vivo. PMID- 22043291 TI - Fluorescent cell barcoding as a tool to assess the age-related development of intracellular cytokine production in small amounts of blood from infants. AB - Fluorescent Cell Barcoding (FCB) is a flow cytometric technique which has been used for assessing signaling proteins. This FCB technique has the potential to be applied in other multiparameter analyses. Since data on antigen (Ag)-specific T cell immune responses, like intracellular cytokine production, are still lacking in infants because limited blood volumes can be obtained for analysis, the FCB technique could be very useful for this purpose. The objectives of this study were to modify the FCB method to be able to measure multiple Ag-specific cytokine reponses in T-cells upon simultaneous stimulation by various antigens and mitogens in small amounts of blood and to investigate the cytokine pattern of T cell subsets in healthy infants aged six and twelve months. Blood samples, collected from 20 healthy infants aged six and twelve months, were stimulated in vitro with the antigens: phorbol-myristate-acetate (PMA), purified-protein derivative (PPD), Tetanus-toxoid (TT), Staphylococcal-enterotoxin-B (SEB), and phytohemagglutinin (PHA). Each stimulus was barcoded by labelling with different intensities of fluorescent cell barcoding (FCB) markers. Intracellular production of interleukin-2, interferon-gamma, and tumor necrosis factor-alpha was measured simultaneously in just one blood sample of 600 ul whole blood. Significant age related differences in cytokine production were shown for PMA, PHA, and TT in CD4(+) T-cells, and for PMA, PHA, SEB, and TT in CD8(+) T-cells. The intracellular cytokine production by CD4(+) and CD8(+) T-cells was higher at twelve months compared to six months of age for all antigens, except for PMA, which was lower at the age of twelve months. Based on the consistency in both T cell subsets, we conclude that the new FCB method is a promising tool to investigate the age-related development of intracellular cytokine production in infants. PMID- 22043292 TI - Dinosaur speed demon: the caudal musculature of Carnotaurus sastrei and implications for the evolution of South American abelisaurids. AB - In the South American abelisaurids Carnotaurus sastrei, Aucasaurus garridoi, and, to a lesser extent Skorpiovenator bustingorryi, the anterior caudal ribs project at a high dorsolateral inclination and have interlocking lateral tips. This unique morphology facilitated the expansion of the caudal hypaxial musculature at the expense of the epaxial musculature. Distinct ridges on the ventrolateral surfaces of the caudal ribs of Aucasaurus garridoi are interpreted as attachment scars from the intra caudofemoralis/ilio-ischiocaudalis septa, and confirm that the M. caudofemoralis of advanced South American abelisaurids originated from a portion of the caudal ribs. Digital muscle models indicate that, relative to its overall body size, Carnotaurus sastrei had a substantially larger M. caudofemoralis than any other theropod yet studied. In most non-avian theropods, as in many extant sauropsids, the M. caudofemoralis served as the primary femoral retractor muscle during the locomotive power stroke. This large investment in the M. caudofemoralis suggests that Carnotaurus sastrei had the potential for great cursorial abilities, particularly short-burst sprinting. However, the tightly interlocking morphology of the anterior caudal vertebrae implies a reduced ability to make tight turns. Examination of these vertebral traits in evolutionary context reveals a progressive sequence of increasing caudofemoral mass and tail rigidity among the Abelisauridae of South America. PMID- 22043293 TI - The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. AB - Modafinil is a mild psychostimulant with pro-cognitive and antidepressant effects. Unlike many conventional stimulants, modafinil has little appreciable potential for abuse, making it a promising therapeutic agent for cocaine addiction. The chief molecular target of modafinil is the dopamine transporter (DAT); however, the mechanistic details underlying modafinil's unique effects remain unknown. Recent studies suggest that the conformational effects of a given DAT ligand influence the magnitude of the ligand's reinforcing properties. For example, the atypical DAT inhibitors benztropine and GBR12909 do not share cocaine's notorious addictive liability, despite having greater binding affinity. Here, we show that the binding mechanism of modafinil is different than cocaine and similar to other atypical inhibitors. We previously established two mutations (W84L and D313N) that increase the likelihood that the DAT will adopt an outward facing conformational state--these mutations increase the affinity of cocaine like inhibitors considerably, but have little or opposite effect on atypical inhibitor binding. Thus, a compound's WT/mutant affinity ratio can indicate whether the compound preferentially interacts with a more outward- or inward facing conformational state. Modafinil displayed affinity ratios similar to those of benztropine, GBR12909 and bupropion (which lack cocaine-like effects in humans), but far different than those of cocaine, beta-CFT or methylphenidate. Whereas treatment with zinc (known to stabilize an outward-facing transporter state) increased the affinity of cocaine and methylphenidate two-fold, it had little or no effect on the binding of modafinil, benztropine, bupropion or GBR12909. Additionally, computational modeling of inhibitor binding indicated that while beta-CFT and methylphenidate stabilize an "open-to-out" conformation, binding of either modafinil or bupropion gives rise to a more closed conformation. Our findings highlight a mechanistic difference between modafinil and cocaine-like stimulants and further demonstrate that the conformational effects of a given DAT inhibitor influence its phenomenological effects. PMID- 22043294 TI - Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. AB - Recent studies have suggested a bacterial role in the development of autoimmune disorders including type 1 diabetes (T1D). Over 30 billion nucleotide bases of Illumina shotgun metagenomic data were analyzed from stool samples collected from four pairs of matched T1D case-control subjects collected at the time of the development of T1D associated autoimmunity (i.e., autoantibodies). From these, approximately one million open reading frames were predicted and compared to the SEED protein database. Of the 3,849 functions identified in these samples, 144 and 797 were statistically more prevalent in cases and controls, respectively. Genes involved in carbohydrate metabolism, adhesions, motility, phages, prophages, sulfur metabolism, and stress responses were more abundant in cases while genes with roles in DNA and protein metabolism, aerobic respiration, and amino acid synthesis were more common in controls. These data suggest that increased adhesion and flagella synthesis in autoimmune subjects may be involved in triggering a T1D associated autoimmune response. Extensive differences in metabolic potential indicate that autoimmune subjects have a functionally aberrant microbiome. Mining 16S rRNA data from these datasets showed a higher proportion of butyrate-producing and mucin-degrading bacteria in controls compared to cases, while those bacteria that produce short chain fatty acids other than butyrate were higher in cases. Thus, a key rate-limiting step in butyrate synthesis is more abundant in controls. These data suggest that a consortium of lactate- and butyrate-producing bacteria in a healthy gut induce a sufficient amount of mucin synthesis to maintain gut integrity. In contrast, non butyrate-producing lactate-utilizing bacteria prevent optimal mucin synthesis, as identified in autoimmune subjects. PMID- 22043295 TI - Examination of triacylglycerol biosynthetic pathways via de novo transcriptomic and proteomic analyses in an unsequenced microalga. AB - Biofuels derived from algal lipids represent an opportunity to dramatically impact the global energy demand for transportation fuels. Systems biology analyses of oleaginous algae could greatly accelerate the commercialization of algal-derived biofuels by elucidating the key components involved in lipid productivity and leading to the initiation of hypothesis-driven strain improvement strategies. However, higher-level systems biology analyses, such as transcriptomics and proteomics, are highly dependent upon available genomic sequence data, and the lack of these data has hindered the pursuit of such analyses for many oleaginous microalgae. In order to examine the triacylglycerol biosynthetic pathway in the unsequenced oleaginous microalga, Chlorella vulgaris, we have established a strategy with which to bypass the necessity for genomic sequence information by using the transcriptome as a guide. Our results indicate an upregulation of both fatty acid and triacylglycerol biosynthetic machinery under oil-accumulating conditions, and demonstrate the utility of a de novo assembled transcriptome as a search model for proteomic analysis of an unsequenced microalga. PMID- 22043296 TI - In vivo SPECT reporter gene imaging of regulatory T cells. AB - Regulatory T cells (Tregs) were identified several years ago and are key in controlling autoimmune diseases and limiting immune responses to foreign antigens, including alloantigens. In vivo imaging techniques including intravital microscopy as well as whole body imaging using bioluminescence probes have contributed to the understanding of in vivo Treg function, their mechanisms of action and target cells. Imaging of the human sodium/iodide symporter via Single Photon Emission Computed Tomography (SPECT) has been used to image various cell types in vivo. It has several advantages over the aforementioned imaging techniques including high sensitivity, it allows non-invasive whole body studies of viable cell migration and localisation of cells over time and lastly it may offer the possibility to be translated to the clinic. This study addresses whether SPECT/CT imaging can be used to visualise the migratory pattern of Tregs in vivo. Treg lines derived from CD4(+)CD25(+)FoxP3(+) cells were retrovirally transduced with a construct encoding for the human Sodium Iodide Symporter (NIS) and the fluorescent protein mCherry and stimulated with autologous DCs. NIS expressing self-specific Tregs were specifically radiolabelled in vitro with Technetium-99m pertechnetate ((99m)TcO(4)(-)) and exposure of these cells to radioactivity did not affect cell viability, phenotype or function. In addition adoptively transferred Treg-NIS cells were imaged in vivo in C57BL/6 (BL/6) mice by SPECT/CT using (99m)TcO(4)(-). After 24 hours NIS expressing Tregs were observed in the spleen and their localisation was further confirmed by organ biodistribution studies and flow cytometry analysis. The data presented here suggests that SPECT/CT imaging can be utilised in preclinical imaging studies of adoptively transferred Tregs without affecting Treg function and viability thereby allowing longitudinal studies within disease models. PMID- 22043298 TI - Human-related factors regulate the spatial ecology of domestic cats in sensitive areas for conservation. AB - BACKGROUND: Domestic cats ranging freely in natural areas are a conservation concern due to competition, predation, disease transmission or hybridization with wildcats. In order to improve our ability to design effective control policies, we investigate the factors affecting their numbers and space use in natural areas of continental Europe. METHODOLOGY/PRINCIPAL FINDINGS: We describe the patterns of cat presence, abundance and space use and analyse the associated environmental and human constraints in a well-preserved Mediterranean natural area with small scattered local farms. We failed in detecting cats in areas away from human settlements (trapping effort above 4000 trap-nights), while we captured 30 individuals near inhabited farms. We identified 130 cats, all of them in farms still in use by people (30% of 128 farms). All cats were free-ranging and very wary of people. The main factor explaining the presence of cats was the presence of people, while the number of cats per farm was mostly affected by the occasional food provisioning with human refuse and the presence of people. The home ranges of eight radio tagged cats were centred at inhabited farms. Males went furthest away from the farms during the mating season (3.8 km on average, maximum 6.3 km), using inhabited farms as stepping-stones in their mating displacements (2.2 km of maximum inter-farm distance moved). In their daily movements, cats notably avoided entering in areas with high fox density. CONCLUSIONS: The presence, abundance and space use of cats were heavily dependent on human settlements. Any strategy aiming at reducing their impact in areas of conservation concern should aim at the presence of settlements and their spatial spread and avoid any access to human refuse. The movements of domestic cats would be limited in areas with large patches of natural vegetation providing good conditions for other carnivore mammals such as red foxes. PMID- 22043297 TI - Screening of feral and wood pigeons for viruses harbouring a conserved mobile viral element: characterization of novel Astroviruses and Picornaviruses. AB - A highly conserved RNA-motif of yet unknown function, called stem-loop-2-like motif (s2m), has been identified in the 3' end of the genomes of viruses belonging to different RNA virus families which infect a broad range of mammal and bird species, including Astroviridae, Picornaviridae, Coronaviridae and Caliciviridae. Since s2m is such an extremely conserved motif, it is an ideal target for screening for viruses harbouring it. In this study, we have detected and characterized novel viruses harbouring this motif in pigeons by using a s2m specific amplification. 84% and 67% of the samples from feral pigeons and wood pigeons, respectively, were found to contain a virus harbouring s2m. Four novel viruses were identified and characterized. Two of the new viruses belong to the genus Avastrovirus in the Astroviridae family. We propose two novel species to be included in this genus, Feral pigeon astrovirus and Wood pigeon astrovirus. Two other novel viruses, Pigeon picornavirus A and Pigeon picornavirus B, belong to the Picornaviridae family, presumably to the genus Sapelovirus. Both of the novel picornaviruses harboured two adjacent s2m, called (s2m)(2), suggesting a possible increased functional effect of s2m when present in two copies. PMID- 22043299 TI - Temperature effects on Agrobacterium phytochrome Agp1. AB - Phytochromes are widely distributed biliprotein photoreceptors with a conserved N terminal chromophore-binding domain. Most phytochromes bear a light-regulated C terminal His kinase or His kinase-like region. We investigated the effects of light and temperature on the His kinase activity of the phytochrome Agp1 from Agrobacterium tumefaciens. As in earlier studies, the phosphorylation activity of the holoprotein after far-red irradiation (where the red-light absorbing Pr form dominates) was stronger than that of the holoprotein after red irradiation (where the far red-absorbing Pfr form dominates). Phosphorylation activities of the apoprotein, far red-irradiated holoprotein, and red-irradiated holoprotein decreased when the temperature increased from 25 degrees C to 35 degrees C; at 40 degrees C, almost no kinase activity was detected. The activity of a holoprotein sample incubated at 40 degrees C was nearly completely restored when the temperature returned to 25 degrees C. UV/visible spectroscopy indicated that the protein was not denatured up to 45 degrees C. At 50 degrees C, however, Pfr denatured faster than the dark-adapted sample containing the Pr form of Agp1. The Pr visible spectrum was unaffected by temperatures of 20-45 degrees C, whereas irradiated samples exhibited a clear temperature effect in the 30-40 degrees C range in which prolonged irradiation resulted in the photoconversion of Pfr into a new spectral species termed Prx. Pfr to Prx photoconversion was dependent on the His-kinase module of Agp1; normal photoconversion occurred at 40 degrees C in the mutant Agp1-M15, which lacks the C-terminal His-kinase module, and in a domain-swap mutant in which the His-kinase module of Agp1 is replaced by the His kinase/response regulator module of the other A. tumefaciens phytochrome, Agp2. The temperature-dependent kinase activity and spectral properties in the physiological temperature range suggest that Agp1 serves as an integrated light and temperature sensor in A. tumefaciens. PMID- 22043300 TI - Desiccation risk drives the spatial ecology of an invasive anuran (Rhinella marina) in the Australian semi-desert. AB - Some invasive species flourish in places that impose challenges very different from those faced in their native geographic ranges. Cane toads (Rhinella marina) are native to tropical and subtropical habitats of South and Central America, but have colonised extremely arid regions over the course of their Australian invasion. We radio-tracked 44 adult cane toads at a semi-arid invasion front to investigate how this invasive anuran has managed to expand its geographic range into arid areas that lie outside of its native climatic niche. As predicted from their low physiological control over rates of evaporative water loss, toads selected diurnal shelter sites that were consistently cooler and damper (and thus, conferred lower water loss rates) than nearby random sites. Desiccation risk also had a profound influence on rates of daily movement. Under wet conditions, toads that were far from water moved further between shelter sites than did conspecifics that remained close to water, presumably in an attempt to reach permanent water sources. However, this relationship was reversed under dry conditions, such that only toads that were close to permanent water bodies made substantial daily movements. Toads that were far from water bodies also travelled along straighter paths than did conspecifics that generally remained close to water. Thus, behavioural flexibility--in particular, an ability to exploit spatial and temporal heterogeneity in the availability of moist conditions--has allowed this invasive anuran to successfully colonize arid habitats in Australia. This finding illustrates that risk assessment protocols need to recognise that under some circumstances an introduced species may be able to thrive in conditions far removed from any that it experiences in its native range. PMID- 22043301 TI - Survival outcomes and effect of early vs. deferred cART among HIV-infected patients diagnosed at the time of an AIDS-defining event: a cohort analysis. AB - OBJECTIVES: We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). METHODS: Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997-2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (<30 days after AIDS event) or deferred (30-270 days after AIDS event) cART. RESULTS: The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/uL and 5.2 (4.5, 5.7) log(10) copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p = 0.20). CONCLUSIONS: Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV infected patients diagnosed with clinical AIDS in our setting. PMID- 22043302 TI - N-CAM exhibits a regulatory function in pathological angiogenesis in oxygen induced retinopathy. AB - BACKGROUND: Diabetic retinopathy and retinopathy of prematurity are diseases caused by pathological angiogenesis in the retina as a consequence of local hypoxia. The underlying mechanism for epiretinal neovascularization (tuft formation), which contributes to blindness, has yet to be identified. Neural cell adhesion molecule (N-CAM) is expressed by Muller cells and astrocytes, which are in close contact with the retinal vasculature, during normal developmental angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Notably, during oxygen induced retinopathy (OIR) N-CAM accumulated on astrocytes surrounding the epiretinal tufts. Here, we show that N-CAM ablation results in reduced vascular tuft formation due to reduced endothelial cell proliferation despite an elevation in VEGFA mRNA expression, whereas retinal developmental angiogenesis was unaffected. CONCLUSION/SIGNIFICANCE: We conclude that N-CAM exhibits a regulatory function in pathological angiogenesis in OIR. This is a novel finding that can be of clinical relevance in diseases associated with proliferative vasculopathy. PMID- 22043303 TI - Comparative proteomic analysis of differentially expressed proteins in the urine of reservoir hosts of leptospirosis. AB - Rattus norvegicus is a natural reservoir host for pathogenic species of Leptospira. Experimentally infected rats remain clinically normal, yet persistently excrete large numbers of leptospires from colonized renal tubules via urine, despite a specific host immune response. Whilst persistent renal colonization and shedding is facilitated in part by differential antigen expression by leptospires to evade host immune responses, there is limited understanding of kidney and urinary proteins expressed by the host that facilitates such biological equilibrium. Urine pellets were collected from experimentally infected rats shedding leptospires and compared to urine from non infected controls spiked with in vitro cultivated leptospires for analysis by 2-D DIGE. Differentially expressed host proteins include membrane metallo endopeptidase, napsin A aspartic peptidase, vacuolar H+ATPase, kidney aminopeptidase and immunoglobulin G and A. Loa22, a virulence factor of Leptospira, as well as the GroEL, were increased in leptospires excreted in urine compared to in vitro cultivated leptospires. Urinary IgG from infected rats was specific for leptospires. Results confirm differential protein expression by both host and pathogen during chronic disease and include markers of kidney function and immunoglobulin which are potential biomarkers of infection. PMID- 22043304 TI - Multiple TORC1-associated proteins regulate nitrogen starvation-dependent cellular differentiation in Saccharomyces cerevisiae. AB - BACKGROUND: The budding yeast Saccharomyces cerevisiae undergoes differentiation into filamentous-like forms and invades the growth medium as a foraging response to nutrient and environmental stresses. These developmental responses are under the downstream control of effectors regulated by the cAMP/PKA and MAPK pathways. However, the upstream sensors and signals that induce filamentous growth through these signaling pathways are not fully understood. Herein, through a biochemical purification of the yeast TORC1 (Target of Rapamycin Complex 1), we identify several proteins implicated in yeast filamentous growth that directly associate with the TORC1 and investigate their roles in nitrogen starvation-dependent or independent differentiation in yeast. METHODOLOGY: We isolated the endogenous TORC1 by purifying tagged, endogenous Kog1p, and identified associated proteins by mass spectrometry. We established invasive and pseudohyphal growth conditions in two S. cerevisiae genetic backgrounds (Sigma1278b and CEN.PK). Using wild type and mutant strains from these genetic backgrounds, we investigated the roles of TORC1 and associated proteins in nitrogen starvation-dependent diploid pseudohyphal growth as well as nitrogen starvation-independent haploid invasive growth. CONCLUSIONS: We show that several proteins identified as associated with the TORC1 are important for nitrogen starvation-dependent diploid pseudohyphal growth. In contrast, invasive growth due to other nutritional stresses was generally not affected in mutant strains of these TORC1-associated proteins. Our studies suggest a role for TORC1 in yeast differentiation upon nitrogen starvation. Our studies also suggest the CEN.PK strain background of S. cerevisiae may be particularly useful for investigations of nitrogen starvation induced diploid pseudohyphal growth. PMID- 22043305 TI - Up-regulation of NDRG2 in senescent lens epithelial cells contributes to age related cataract in human. AB - BACKGROUND: Human N-Myc downstream regulated gene2 (NDRG2), a novel gene has been cloned and shown to be related to a number of cellular processes, including proliferation, differentiation, stress, and apoptosis. NDRG2 has also been linked to age-related Alzheimer's disease. Since the role of this gene in senescence is limited, we have investigated the potential role of NDRG2 in human lens epithelial cells (HLECs), a paradigm implicated in age-related cataract. METHODOLOGY/PRINCIPAL FINDINGS: Cultured HLECs (SRA01/04) were subjected to prolonged exposure to low dose of H(2)O(2) to simulate senescence. After being exposed to 50 uM H(2)O(2) for 2 weeks, HLECs senescent-morphological changes appeared, cell viability decreased dramatically, cell proliferation reduced from 37.4% to 16.1%, and senescence-associated beta-galactosidase activity increased from 0 to 90.3%. Ndrg2 protein expression was also significantly increased in these senescent cells. To induce overexpression of NDRG2, SRA01/04 cells were infected with the adenoviral vector of NDRG2. In these cells, overexpression of NDRG2 resulted in a fibroblast-like appearance and the cell viability decreased about 20%. In addition, the NDRG2-overexpression cells demonstrated 20% lower viability when exposed to 50-200 uM H(2)O(2) for acute oxidative stress. Furthermore, the expression of NDRG2 from age-related cataracts was up-regulated 2-fold at both mRNA and protein levels compared with the clear lenses. CONCLUSIONS/SIGNIFICANCE: NDRG2 is up regulated not only in the ageing process of HLECs in vitro but also in the cells from human age-related cortical cataract in vivo. Up-regulation of NDRG2 induces cell morphological changes, reduces cell viability, and especially lowers cellular resistance to oxidative stress. NDRG2 mediated affects in HLECs may associate with age-related cataract formation. PMID- 22043306 TI - Direct identification of insulator components by insertional chromatin immunoprecipitation. AB - Comprehensive understanding of mechanisms of epigenetic regulation requires identification of molecules bound to genomic regions of interest in vivo. However, non-biased methods to identify molecules bound to specific genomic loci in vivo are limited. Here, we applied insertional chromatin immunoprecipitation (iChIP) to direct identification of components of insulator complexes, which function as boundaries of chromatin domain. We found that the chicken beta-globin HS4 (cHS4) insulator complex contains an RNA helicase protein, p68/DDX5; an RNA species, steroid receptor RNA activator 1; and a nuclear matrix protein, Matrin 3, in vivo. Binding of p68 and Matrin-3 to the cHS4 insulator core sequence was mediated by CCCTC-binding factor (CTCF). Thus, our results showed that it is feasible to directly identify proteins and RNA bound to a specific genomic region in vivo by using iChIP. PMID- 22043307 TI - Effect of oxidative stress on homer scaffolding proteins. AB - Homer proteins are a family of multifaceted scaffolding proteins that participate in the organization of signaling complexes at the post-synaptic density and in a variety of tissues including striated muscle. Homer isoforms form multimers via their C-terminal coiled coil domains, which allows for the formation of a polymeric network in combination with other scaffolding proteins. We hypothesized that the ability of Homer isoforms to serve as scaffolds would be influenced by oxidative stress. We have found by standard SDS-PAGE of lysates from adult mouse skeletal muscle exposed to air oxidation that Homer migrates as both a dimer and monomer in the absence of reducing agents and solely as a monomer in the presence of a reducing agent, suggesting that Homer dimers exposed to oxidation could be modified by the presence of an inter-molecular disulfide bond. Analysis of the peptide sequence of Homer 1b revealed the presence of only two cysteine residues located adjacent to the C-terminal coiled-coil domain. HEK 293 cells were transfected with wild-type and cysteine mutant forms of Homer 1b and exposed to oxidative stress by addition of menadione, which resulted in the formation of disulfide bonds except in the double mutant (C246G, C365G). Exposure of myofibers from adult mice to oxidative stress resulted in decreased solubility of endogenous Homer isoforms. This change in solubility was dependent on disulfide bond formation. In vitro binding assays revealed that cross-linking of Homer dimers enhanced the ability of Homer 1b to bind Drebrin, a known interacting partner. Our results show that oxidative stress results in disulfide cross linking of Homer isoforms and loss of solubility of Homer scaffolds. This suggests that disulfide cross-linking of a Homer polymeric network may contribute to the pathophysiology seen in neurodegenerative diseases and myopathies characterized by oxidative stress. PMID- 22043308 TI - RNA-Seq analyses generate comprehensive transcriptomic landscape and reveal complex transcript patterns in hepatocellular carcinoma. AB - RNA-seq is a powerful tool for comprehensive characterization of whole transcriptome at both gene and exon levels and with a unique ability of identifying novel splicing variants. To date, RNA-seq analysis of HBV-related hepatocellular carcinoma (HCC) has not been reported. In this study, we performed transcriptome analyses for 10 matched pairs of cancer and non-cancerous tissues from HCC patients on Solexa/Illumina GAII platform. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for samples sequenced on each lane, which was able to identify >50% of all the annotated genes for each sample. Furthermore, we identified 1,378 significantly differently expressed genes (DEGs) and 24, 338 differentially expressed exons (DEEs). Comprehensive function analyses indicated that cell growth-related, metabolism related and immune-related pathways were most significantly enriched by DEGs, pointing to a complex mechanism for HCC carcinogenesis. Positional gene enrichment analysis showed that DEGs were most significantly enriched at chromosome 8q21.3-24.3. The most interesting findings were from the analysis at exon levels where we characterized three major patterns of expression changes between gene and exon levels, implying a much complex landscape of transcript specific differential expressions in HCC. Finally, we identified a novel highly up-regulated exon-exon junction in ATAD2 gene in HCC tissues. Overall, to our best knowledge, our study represents the most comprehensive characterization of HBV-related HCC transcriptome including exon level expression changes and novel splicing variants, which illustrated the power of RNA-seq and provided important clues for understanding the molecular mechanisms of HCC pathogenesis at system wide levels. PMID- 22043309 TI - Severe obstetric brachial plexus palsies can be identified at one month of age. AB - OBJECTIVE: To establish whether severe obstetric brachial plexus palsy (OBPP) can be identified reliably at or before three months of age. METHODS: Severe OBPP was defined as neurotmesis or avulsion of spinal nerves C5 and C6 irrespective of additional C7-T1 lesions, assessed during surgery and confirmed by histopathological examination. We first prospectively studied a derivation group of 48 infants with OBPP with a minimal follow-up of two years. Ten dichotomous items concerning active clinical joint movement and needle electromyography of the deltoid, biceps and triceps muscles were gathered at one week, one month and three months of age. Predictors for a severe lesion were identified using a two step forward logistic regression analysis. The results were validated in two independent cohorts of OBPP infants of 60 and 13 infants. RESULTS: Prediction of severe OBPP at one month of age was better than at one week and at three months. The presence of elbow extension, elbow flexion and of motor unit potentials in the biceps muscle correctly predicted whether lesions were mild or severe in 93.6% of infants in the derivation group (sensitivity 1.0, specificity 0.88), in 88.3% in the first validation group (sensitivity 0.97, specificity 0.76) and in 84.6% in the second group (sensitivity of 1.0, specificity 0.66). INTERPRETATION: Infants with OBPP with severe lesions can be identified at one month of age by testing elbow extension, elbow flexion and recording motor unit potentials (MUPs) in the biceps muscle. The decision rule implies that children without active elbow extension at one month should be referred to a specialized center, while children with active elbow extension as well as active flexion should not. When there is active elbow extension, but no active elbow flexion an EMG is needed; absence of MUPs in the biceps muscle is an indication for referral. PMID- 22043310 TI - Patients' and observers' perceptions of involvement differ. Validation study on inter-relating measures for shared decision making. AB - OBJECTIVE: Patient involvement into medical decisions as conceived in the shared decision making method (SDM) is essential in evidence based medicine. However, it is not conclusively evident how best to define, realize and evaluate involvement to enable patients making informed choices. We aimed at investigating the ability of four measures to indicate patient involvement. While use and reporting of these instruments might imply wide overlap regarding the addressed constructs this assumption seems questionable with respect to the diversity of the perspectives from which the assessments are administered. METHODS: The study investigated a nested cohort (N = 79) of a randomized trial evaluating a patient decision aid on immunotherapy for multiple sclerosis. Convergent validities were calculated between observer ratings of videotaped physician-patient consultations (OPTION) and patients' perceptions of the communication (Shared Decision Making Questionnaire, Control Preference Scale & Decisional Conflict Scale). RESULTS: OPTION reliability was high to excellent. Communication performance was low according to OPTION and high according to the three patient administered measures. No correlations were found between observer and patient judges, neither for means nor for single items. Patient report measures showed some moderate correlations. CONCLUSION: Existing SDM measures do not refer to a single construct. A gold standard is missing to decide whether any of these measures has the potential to indicate patient involvement. PRACTICE IMPLICATIONS: Pronounced heterogeneity of the underpinning constructs implies difficulties regarding the interpretation of existing evidence on the efficacy of SDM. Consideration of communication theory and basic definitions of SDM would recommend an inter subjective focus of measurement. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN25267500. PMID- 22043311 TI - A systematic screen for micro-RNAs regulating the canonical Wnt pathway. AB - MicroRNAs (miRs) and the canonical Wnt pathway are known to be dysregulated in human cancers and play key roles during cancer initiation and progression. To identify miRs that can modulate the activity of the Wnt pathway we performed a cell-based overexpression screen of 470 miRs in human HEK293 cells. We identified 38 candidate miRs that either activate or repress the canonical Wnt pathway. A literature survey of all verified candidate miRs revealed that the Wnt-repressing miRs tend to be anti-oncomiRs and down-regulated in cancers while Wnt-activating miRs tend to be oncomiRs and upregulated during tumorigenesis. Epistasis-based functional validation of three candidate miRs, miR-1, miR-25 and miR-613, confirmed their inhibitory role in repressing the Wnt pathway and suggest that while miR-25 may function at the level of a-catenin (beta-cat), miR-1 and miR-613 act upstream of beta-cat. Both miR-25 and miR-1 inhibit cell proliferation and viability during selection of human colon cancer cell lines that exhibit dysregulated Wnt signaling. Finally, transduction of miR-1 expressing lentiviruses into primary mammary organoids derived from Conductin-lacZ mice significantly reduced the expression of the Wnt-sensitive beta-gal reporter. In summary, these findings suggest the potential use of Wnt-modulating miRs as diagnostic and therapeutic tools in Wnt-dependent diseases, such as cancer. PMID- 22043312 TI - Molecular evolution of the rice blast resistance gene Pi-ta in invasive weedy rice in the USA. AB - The Pi-ta gene in rice has been effectively used to control rice blast disease caused by Magnaporthe oryzae worldwide. Despite a number of studies that reported the Pi-ta gene in domesticated rice and wild species, little is known about how the Pi-ta gene has evolved in US weedy rice, a major weed of rice. To investigate the genome organization of the Pi-ta gene in weedy rice and its relationship to gene flow between cultivated and weedy rice in the US, we analyzed nucleotide sequence variation at the Pi-ta gene and its surrounding 2 Mb region in 156 weedy, domesticated and wild rice relatives. We found that the region at and around the Pi-ta gene shows very low genetic diversity in US weedy rice. The patterns of molecular diversity in weeds are more similar to cultivated rice (indica and aus), which have never been cultivated in the US, rather than the wild rice species, Oryza rufipogon. In addition, the resistant Pi-ta allele (Pi ta) found in the majority of US weedy rice belongs to the weedy group strawhull awnless (SH), suggesting a single source of origin for Pi-ta. Weeds with Pi-ta were resistant to two M. oryzae races, IC17 and IB49, except for three accessions, suggesting that component(s) required for the Pi-ta mediated resistance may be missing in these accessions. Signatures of flanking sequences of the Pi-ta gene and SSR markers on chromosome 12 suggest that the susceptible pi-ta allele (pi-ta), not Pi-ta, has been introgressed from cultivated to weedy rice by out-crossing. PMID- 22043313 TI - Erythropoietin ameliorates rat experimental autoimmune neuritis by inducing transforming growth factor-beta in macrophages. AB - Erythropoietin (EPO) is a pleiotropic cytokine originally identified for its role in erythropoiesis. In addition, in various preclinical models EPO exhibited protective activity against tissue injury. There is an urgent need for potent treatments of autoimmune driven disorders of the peripheral nervous system (PNS), such as the Guillain-Barre syndrome (GBS), a disabling autoimmune disease associated with relevant morbidity and mortality. To test the therapeutic potential of EPO in experimental autoimmune neuritis (EAN) - an animal model of human GBS--immunological and clinical effects were investigated in a preventive and a therapeutic paradigm. Treatment with EPO reduced clinical disease severity and if given therapeutically also shortened the recovery phase of EAN. Clinical findings were mirrored by decreased inflammation within the peripheral nerve, and myelin was well maintained in treated animals. In contrast, EPO increased the number of macrophages especially in later stages of the experimental disease phase. Furthermore, the anti-inflammatory cytokine transforming growth factor (TGF)-beta was upregulated in the treated cohorts. In vitro experiments revealed less proliferation of T cells in the presence of EPO and TGF-beta was moderately induced, while the secretion of other cytokines was almost not altered by EPO. Our data suggest that EPO revealed its beneficial properties by the induction of beneficial macrophages and the modulation of the immune system towards anti inflammatory responses in the PNS. Further studies are warranted to elaborate the clinical usefulness of EPO for treating immune-mediated neuropathies in affected patients. PMID- 22043314 TI - Neuropathologic correlates of hippocampal atrophy in the elderly: a clinical, pathologic, postmortem MRI study. AB - The volume of the hippocampus measured with structural magnetic resonance imaging (MRI) is increasingly used as a biomarker for Alzheimer's disease (AD). However, the neuropathologic basis of structural MRI changes in the hippocampus in the elderly has not been directly assessed. Postmortem MRI of the aging human brain, combined with histopathology, could be an important tool to address this issue. Therefore, this study combined postmortem MRI and histopathology in 100 elderly subjects from the Rush Memory and Aging Project and the Religious Orders Study. First, to validate the information contained in postmortem MRI data, we tested the hypothesis that postmortem hippocampal volume is smaller in subjects with clinically diagnosed Alzheimer's disease compared to subjects with mild or no cognitive impairment, as observed in antemortem imaging studies. Subsequently, the relations of postmortem hippocampal volume to AD pathology, Lewy bodies, amyloid angiopathy, gross infarcts, microscopic infarcts, and hippocampal sclerosis were examined. It was demonstrated that hippocampal volume was smaller in persons with a clinical diagnosis of AD compared to those with no cognitive impairment (P = 2.6 * 10(-7)) or mild cognitive impairment (P = 9.6 * 10(-7)). Additionally, hippocampal volume was related to multiple cognitive abilities assessed proximate to death, with its strongest association with episodic memory. Among all pathologies investigated, the most significant factors related to lower hippocampal volume were shown to be AD pathology (P = 0.0018) and hippocampal sclerosis (P = 4.2 * 10(-7)). Shape analysis allowed for visualization of the hippocampal regions most associated with volume loss for each of these two pathologies. Overall, this investigation confirmed the relation of hippocampal volume measured postmortem to clinical diagnosis of AD and measures of cognition, and concluded that both AD pathology and hippocampal sclerosis affect hippocampal volume in old age, though the impacts of each pathology on the shape of the hippocampus may differ. PMID- 22043315 TI - Lysine 92 amino acid residue of USP46, a gene associated with 'behavioral despair' in mice, influences the deubiquitinating enzyme activity. AB - Deubiquitinating enzymes (DUBs) regulate diverse cellular functions by their activity of cleaving ubiquitin from specific protein substrates. Ubiquitin Specific Protease 46 (USP46) has recently been identified as a quantitative trait gene responsible for immobility in the tail suspension test and forced swimming test in mice. Mice with a lysine codon (Lys 92) deletion in USP46 exhibited loss of 'behavioral despair' under inescapable stresses in addition to abnormalities in circadian behavioral rhythms and the GABAergic system. However, whether this deletion affects enzyme activity is unknown. Here we show that USP46 has deubiquitinating enzyme activity detected by USP cleavage assay using GST-Ub52 as a model substrate. Interestingly, compared to wild type, the Lys 92 deletion mutant resulted in a decreased deubiquitinating enzyme activity of 27.04%. We also determined the relative expression levels of Usp46 in rat tissues using real time RT-PCR. Usp46 mRNA was expressed in various tissues examined including brain, with the highest expression in spleen. In addition, like rat USP46, both human and mouse USP46 are active toward to the model substrate, indicating the USP cleavage assay is a simple method for testing the deubiquitinating enzyme activity of USP46. These results suggest that the Lys 92 deletion of USP46 could influence enzyme activity and thereby provide a molecular clue how the enzyme regulating the pathogenesis of mental illnesses. PMID- 22043316 TI - Minimal functional sites allow a classification of zinc sites in proteins. AB - Zinc is indispensable to all forms of life as it is an essential component of many different proteins involved in a wide range of biological processes. Not differently from other metals, zinc in proteins can play different roles that depend on the features of the metal-binding site. In this work, we describe zinc sites in proteins with known structure by means of three-dimensional templates that can be automatically extracted from PDB files and consist of the protein structure around the metal, including the zinc ligands and the residues in close spatial proximity to the ligands. This definition is devised to intrinsically capture the features of the local protein environment that can affect metal function, and corresponds to what we call a minimal functional site (MFS). We used MFSs to classify all zinc sites whose structures are available in the PDB and combined this classification with functional annotation as available in the literature. We classified 77% of zinc sites into ten clusters, each grouping zinc sites with structures that are highly similar, and an additional 16% into seven pseudo-clusters, each grouping zinc sites with structures that are only broadly similar. Sites where zinc plays a structural role are predominant in eight clusters and in two pseudo-clusters, while sites where zinc plays a catalytic role are predominant in two clusters and in five pseudo-clusters. We also analyzed the amino acid composition of the coordination sphere of zinc as a function of its role in the protein, highlighting trends and exceptions. In a period when the number of known zinc proteins is expected to grow further with the increasing awareness of the cellular mechanisms of zinc homeostasis, this classification represents a valuable basis for structure-function studies of zinc proteins, with broad applications in biochemistry, molecular pharmacology and de novo protein design. PMID- 22043317 TI - ATP competitive protein kinase C inhibitors demonstrate distinct state-dependent inhibition. AB - We previously reported that some ATP competitive protein kinase C (PKC) inhibitors are either competitive or uncompetitive inhibitors with respect to substrate peptides. In this report, we demonstrate how the interactions between PKC and inhibitors change PKC activation kinetics. A substrate competitive inhibitor, bisindolylmaleimide I, targets activated PKC and stabilizes PKC in the activated conformation. This leads to transient activation and prolonged deactivation of PKC in the presence of bisindolylmaleimide I. In contrast, an uncompetitive substrate inhibitor, bisindolylmaleimide IV, targets quiescent PKC and stabilizes PKC in the quiescent conformation, which generates slower activation and suppressed translocation upon activation of PKC. PMID- 22043318 TI - Migfilin and filamin as regulators of integrin activation in endothelial cells and neutrophils. AB - Cell adhesion and migration depend on engagement of extracellular matrix ligands by integrins. Integrin activation is dynamically regulated by interactions of various cytoplasmic proteins, such as filamin and integrin activators, talin and kindlin, with the cytoplasmic tail of the integrin beta subunit. Although filamin has been suggested to be an inhibitor of integrin activation, direct functional evidence for the inhibitory role of filamin is limited. Migfilin, a filamin binding protein enriched at cell-cell and cell-extracellular matrix contact sites, can displace filamin from beta1 and beta3 integrins and promote integrin activation. However, its role in activation and functions of different beta integrins in human vascular cells is unknown. In this study, using flow cytometry, we demonstrate that filamin inhibits beta1 and alphaIIbbeta3 integrin activation, and migfilin can overcome its inhibitory effect. Migfilin protein is widely expressed in different adherent and circulating blood cells and can regulate integrin activation in naturally-occurring vascular cells, endothelial cells and neutrophils. Migfilin can activate beta1, beta2 and beta3 integrins and promote integrin mediated responses while migfilin depletion impairs the spreading and migration of endothelial cells. Thus, filamin can act broadly as an inhibitor and migfilin is a promoter of integrin activation. PMID- 22043319 TI - UV-sensitive photoreceptor protein OPN5 in humans and mice. AB - A variety of animal species utilize the ultraviolet (UV) component of sunlight as their environmental cues, whereas physiological roles of UV photoreception in mammals, especially in human beings, remain open questions. Here we report that mouse neuropsin (OPN5) encoded by the Opn5 gene exhibited an absorption maximum (lambdamax) at 380 nm when reconstituted with 11-cis-retinal. Upon UV-light illumination, OPN5 was converted to a blue-absorbing photoproduct (lambdamax 470 nm), which was stable in the dark and reverted to the UV-absorbing state by the subsequent orange light illumination, indicating its bistable nature. Human OPN5 also had an absorption maximum at 380 nm with spectral properties similar to mouse OPN5, revealing that OPN5 is the first and hitherto unknown human opsin with peak sensitivity in the UV region. OPN5 was capable of activating heterotrimeric G protein Gi in a UV-dependent manner. Immuno-blotting analyses of mouse tissue extracts identified the retina, the brain and, unexpectedly, the outer ears as the major sites of OPN5 expression. In the tissue sections of mice, OPN5 immuno-reactivities were detected in a subset of non-rod/non-cone retinal neurons as well as in the epidermal and muscle cells of the outer ears. Most of these OPN5-immuno-reactivities in mice were co-localized with positive signals for the alpha-subunit of Gi. These results demonstrate the first example of UV photoreceptor in human beings and strongly suggest that OPN5 triggers a UV sensitive Gi-mediated signaling pathway in the mammalian tissues. PMID- 22043321 TI - The heart of the matter. PMID- 22043320 TI - Downregulation of RPL6 by siRNA inhibits proliferation and cell cycle progression of human gastric cancer cell lines. AB - Our previous study revealed that human ribosomal protein L6 (RPL6) was up regulated in multidrug-resistant gastric cancer cells and over-expression of RPL6 could protect gastric cancer from drug-induced apoptosis. It was further demonstrated that up-regulation of RPL6 accelerated growth and enhanced in vitro colony forming ability of GES cells while down-regulation of RPL6 exhibited the opposite results. The present study was designed to investigate the potential role of RPL6 in therapy of gastric cancer for clinic. The expression of RPL6 and cyclin E in gastric cancer tissues and normal gastric mucosa was evaluated by immunohistochemisty. It was found that RPL6 and cyclin E were expressed at a higher level in gastric cancer tissues than that in normal gastric mucosa and the two were correlative in gastric cancer. Survival time of postoperative patients was analyzed by Kaplan- Meier analysis and it was found that patients with RPL6 positive expression showed shorter survival time than patients that with RPL6 negative expression. RPL6 was then genetically down-regulated in gastric cancer SGC7901 and AGS cell lines by siRNA. It was demonstrated that down-regulation of RPL6 reduced colony forming ability of gastric cancer cells in vitro and reduced cell growth in vivo. Moreover, down-regulation of RPL6 could suppress G1 to S phase transition in these cells. Further, we evidenced that RPL6 siRNA down regulated cyclin E expression in SGC7901 and AGS cells. Taken together, these data suggested that RPL6 was over-expressed in human gastric tissues and caused poor prognosis. Down-regulation of RPL6 could suppress cell growth and cell cycle progression at least through down-regulating cyclin E and which might be used as a novel approach to gastric cancer therapy. PMID- 22043322 TI - Phase II Study of Capecitabine, Oxaliplatin, and Cetuximab for Advanced Hepatocellular Carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is frequently resistant to chemotherapy. However, epidermal growth factor receptor (EGFR) inhibition has demonstrated activity in HCC and overcomes chemotherapy resistance in other settings. We studied the efficacy of combining the anti-EGFR antibody cetuximab with capecitabine and oxaliplatin in advanced HCC. METHODS: Patients who had chemotherapy-naive advanced/unresectable HCC and any Childs-Pugh-class chronic liver disease (provided bilirubin was <3 mg/dl) received capecitabine 850 mg/m(2) bid days 1-14, oxaliplatin 130 mg/m(2) day 1, and cetuximab 400 mg/m(2) day 1 then 250 mg/m(2) weekly for each 21 day cycle. RESULTS: Twenty-nine patients received any protocol therapy, but 24 completed at least one cycle. Of the 24 patients evaluable for response, 3 had a partial response (12.5%, 95% confidence interval [CI], 3-32%) and 17 had stable disease (71%), for a disease control rate of 83%. Of patients with an elevated AFP, 57% had a >50% reduction in AFP. Median time to progression was 4.5 months (95% CI, 3.2-6.4), and overall survival was 4.4 months (95% CI, 2.4-7.3). Most common toxicities included diarrhea (13 patients, 45%), fatigue (12 patients, 41%), and hypomagnesemia (12 patients, 41%). Fatigue (6 patients) and diarrhea (5 patients) were the most common grade 3 4 toxicities. Three patients died within the first 30 days of treatment (one of toxicity, two of liver failure presumed to be related to disease progression). CONCLUSIONS: The capecitabine/oxaliplatin/cetuximab combination was tolerable, though diarrhea was pronounced, in this population. The combination was associated with a modest response rate, but a high rate of AFP response and radiographic stable disease. Time to progression and overall survival were shorter than would be expected for treatment with sorafenib. PMID- 22043323 TI - Decreased Posttreatment SUV on PET Scan Is Associated With Improved Local Control in Medically Inoperable Esophageal Cancer. AB - BACKGROUND: The relationship between local, regional, or distant disease control (LC, RC, DC) and maximal posttreatment standardized uptake value (SUV(max)) in patients with esophageal cancer has not been elucidated. This study was initiated to explore whether a decrease in SUV on positron emission tomography-computed tomography (PET-CT) scan is associated with LC, RC, or DC in patients with esophageal carcinoma treated with definitive chemoradiotherapy. METHODS: Medical records of 40 patients with inoperable esophageal cancer treated with definitive intent and who underwent pre- and posttreatment PET-CT scans were reviewed. The histology, nodal status, tumor location, and radiotherapy (RT) dose were investigated as variables to determine a relationship between SUV(max) and LC, RC, and DC as well as disease-free survival (DFS). RESULTS: Decreased posttreatment SUV(max) on PET scan (P = .02) and increased RT dose (P = .009) were the only significant predictors of improved LC on univariate analysis. Mean RT doses in patients with no evidence of disease or with local, regional, or distant recurrences were 5,244, 4,580, 5,094, and 4,968, respectively. Decreased posttreatment SUV (P = .03) and increased RT dose (P = .008) were also associated with an improvement in DFS. Furthermore, decreased posttreatment SUV(max) correlated with an improvement in LC (hazard ratio [HR] = 1.3, 95% confidence interval [CI] = 1.03-1.6, P = .03) as well as DFS (HR = 1.3, 95% CI = 1.03-1.6, P = .03). These findings were maintained on multivariate analysis. CONCLUSIONS: Posttreatment decrease in SUV is associated with LC and DFS in esophageal cancer patients receiving definitive chemoradiotherapy. RT dose was also associated with both LC and DFS. The prognostic significance of these findings warrants prospective confirmation. PMID- 22043324 TI - Low-lying rectal cancer with anal canal involvement: abdominoperineal or low anterior resection after neoadjuvant chemoradiotherapy. AB - BACKGROUND: Rectal cancer with anal involvement is typically treated with abdominoperineal resection (APR). However, patients treated with neoadjuvant chemoradiotherapy with good clinical response and tumor regression from the anus present a controversial management dilemma. This is a report of patients treated with low anterior resection (LAR) versus APR. METHODS: Patients with T2-3N0-2M0 (IIA-IIIC) rectal cancer with anal canal involvement were eligible. Anal canal involvement was determined by sigmoidoscopy/colonoscopy or endoscopic ultrasound. Patients were treated in the prone position with the three-field technique to 45 50.4 Gy at 1.8 Gy/fraction given concurrently with 5-fluorouracil. Patients then underwent APR/LAR via total mesorectal excision 4-6 weeks after chemoradiotherapy. LAR was performed in patients with good sphincter function at presentation, in those with sufficient tumor regression away from anal canal to permit LAR, and in those compliant with close follow-up. RESULTS: A total of 32 patients with rectal cancer with anal canal involvement were treated with neoadjuvant chemoradiotherapy. Local control was 85% and 89% for patients treated with APR and LAR, respectively. Overall survival was 76% and 86% in patients treated with APR and LAR, respectively. Pathologic complete response was seen in 24% of patients who underwent APR and 27% of patients who underwent LAR. CONCLUSION: Rectal cancers with anal involvement with good clinical response after neoadjuvant chemoradiotherapy are typically treated with APR. However, LAR may be a feasible alternative, particularly in those with excellent clinical response to neoadjuvant treatment with sufficient tumor regression away from the anal canal. In these patients close follow-up is necessary, and APR may be reserved as salvage when needed. PMID- 22043325 TI - Refining docetaxel-containing therapy for gastric cancer. AB - Gastric cancer-the second most common cause of cancer-related deaths worldwide-is a global health problem. Most cases present at advanced stages and are incurable due to locally advanced or metastatic disease. Although advanced gastric cancer is relatively chemosensitive, a gold standard chemotherapy regimen has yet to emerge, and response rates are of short duration. Cisplatin and 5-fluorouracil (CF) have emerged as the backbone agents in treating this disease. The pivotal V325 trial demonstrated the efficacy benefit of adding docetaxel to CF (DCF). DCF, however, is associated with significant toxicity, making it less tolerable to patients. As a result, docetaxel-containing regimens have been extensively studied and improved upon to mitigate toxicity while maintaining efficacy. Various dosing and scheduling permutations of the original DCF regimen have emerged, and substitutions with other 5-fluorouraci and platinum analogs have been studied. In this review we highlight some of these studies using docetaxel based regimens as well as new approaches using targeted therapy, including monoclonal antibodies and tyrosine kinase inhibitors. Continuing efforts to improve the efficacy and tolerability of docetaxel-based chemotherapy, combining pharmacokinetic parameters and pharmacogenetic correlates, will further assist in developing optimized regimens. Emerging data using targeted therapy and biologics in combination with chemotherapy are promising, but results of ongoing studies are required to establish the safety and efficacy of these regimens. PMID- 22043326 TI - A case for more intensive systemic therapy for patients with locally advanced rectal cancer: even in the face of a pathologic complete response. PMID- 22043327 TI - Invasion of a fundoplication sleeve by esophageal squamous-cell carcinoma. PMID- 22043328 TI - Rare Primitive Neuroectodermal Tumor (PNET) of Liver in a Young Woman. PMID- 22043329 TI - Type 2 Diabetes in Oman: Can we learn from the Lancet editorial. PMID- 22043330 TI - An overview of clinical pharmacology of Ibuprofen. AB - Ibuprofen was the first member of Propionic acid derivatives introduced in 1969. It is a popular domestic and over the counter analgesic and antipyretic for adults and children. Ibuprofen has been rated as the safest conventional NSAID by spontaneous adverse drug reaction reporting systems in the UK. This article summarizes the main pharmacological effects, therapeutical applications and adverse drug reactions, drug-drug interactions and food drug interactions of ibuprofen that have been reported especially during the last 10 years. PMID- 22043331 TI - Care or Cry: Three years from Cyclone Gonu. What have we learnt? AB - OBJECTIVES: This article examines and evaluates the history of natural disasters in Oman and presents the health care response to cyclone Gonu, and highlights the health care lessons learnt from the Cyclone as narrated by frontline personnel and it puts forward some practical recommendations for health care policy makers in order to strengthen the health care disaster preparations to combat future natural and man-made disasters. METHODS: The lessons presented in this article are based on the reflections of frontline health care personnel who witnessed Cyclone Gonu. The reflections of experience collected as a part of a qualitative 17 semi-structured interviews conducted in Oman between December 2009 and January 2010. RESULTS: The study found that the lessons from passes events went by un noticed and exposed some serious fragmentation in the coordination of different governmental sectors involved in emergency management and that there was no well planned mechanism of alert and warning dissemination to people and communities. CONCLUSION: Overall, the major lessons that learnt from Cyclone Gonu would have been very useful if they had been taken into consideration and implemented during the health care response to cyclone Phet. PMID- 22043332 TI - Association between seminal plasma copper and magnesium levels with oxidative stress in iraqi infertile men. AB - OBJECTIVES: To study the association between copper, magnesium and malondialdehyde levels in seminal plasma of oligozoospermic, azoospermic in relation to normozoospermic men. METHODS: The present study was conducted at the Chemistry and Biochemistry department, College of Medicine, Al-Nahrain University, Baghdad-Iraq during September 2007 to February 2008 after obtaining approval from the research and ethics committee and obtaining written consent, 78 infertile men (age range 33.01+/-4.20 years) were recruited at the institute of embryo research and infertility treatment, Al-Kadhimiya teaching hospital, Iraq and were categorized according to their seminal fluid parameters to oligozoospermia (n=43) and azoospermia (n=35). 41 fertile men (age range 30.29+/ 2.30 years) were selected as controls. Seminal plasma copper and magnesium were measured by atomic absorption spectrophotometry. Malondialdehyde was measured calorimetrically using thiobarbituric acid assay which detects thiobarbituric acid reactive substances. RESULTS: Seminal plasma copper level was decreased significantly (p=0.000) in the azoospermic group compared to the control group. Whereas, the level decreased non-significantly in the oligozoospermic group. Seminal plasma magnesium levels were decreased significantly (p=0.000) in all the infertility groups studied. On the other hand, malondialdehyde levels which is an end product of lipid peroxidation were significantly elevated (p=0.000) in all the infertility groups studied. CONCLUSION: Copper and magnesium work in different ways in order to maintain normal environment for spermatozoa for normal fertilization to occur. PMID- 22043333 TI - Tissue Factor, Tissue Factor Pathway Inhibitor and Factor VII Activity in Cardiovascular Complicated Type 2 Diabetes Mellitus. AB - OBJECTIVES: Tissue factor (TF) is the main initiator of the extrinsic coagulation pathway through factor VII (FVII) activation, which is physiologically inhibited by tissue factor pathway inhibitor (TFPI). Alteration of this pathway has been described in Type 2 diabetes mellitus (T2DM). The aim of this study is to assess TF and TFPI plasma levels and FVII coagulant activity (FVIIa) in T2DM in relation to cardiothrombotic disease and their correlation to metabolic and clinical behavior of the patients. METHODS: The study was conducted on 80 T2DM patients divided to accordingly; groupI: 40 patients without a history or clinically detected heart disease, and groupII: 40 patients with a history of myocardial infarction compared to 30 controls. The patients were recruited from Ain Shams University diabetes clinic from September 2007 to February 2009 after informed consent was obtained. Peripheral blood samples were taken for measurement of plasma TF and TFPI levels using ELISA technique and quantitative FVIIa using FVII deficient plasma. RESULTS: Plasma levels of TF, TFPI and FVIIa were significantly higher in T2DM patients compared to the controls (p<0.001). TF (236.50+/ 79.23)and TFPI (242.33+/-85.84)were significantly higher in group II, compared to group I (150.33+/-81.16), (152.8+/- 82.46), (p<0.001). TF and TFPI were significantly correlated to body mass index and glycemic control. Also, TF and TFPI were significantly higher in hypertensives (p=0.001) and dyslipidemics (p=0.006) but not in smokers (p=0.64), (p=0.11) respectively. CONCLUSION: There was a correlation between high TF, TFPI plasma levels, FVIIa activity and cardiothrombotic complications in T2DM especially in the presence of high risk factors such as poor glycemic control, dyslipidemia and obesity. Future target therapy against TF may be beneficial for T2DM patients. PMID- 22043334 TI - Effects of total light deprivation on dorsal lateral geniculate nucleus of male neonate rats. AB - OBJECTIVES: This study examines the effects of total light deprivation on the developing lateral geniculate nucleus, the primary integration centre for visual information METHODS: Sprague-Dawley rats were reared for one month in a dark room from 7th postnatal day before eye opening. A group of rats was taken back into normal condition for 15 days, and then perfused. Coronal sections of LGN were prepared and stained with Cresyl Violet and Cytochrome Oxidase to investigate the number of neurons, volume and length, as well as neuronal activity level. RESULTS: The results showed that LD for one month causes progressive loss of neurons and decreases neuronal activity level in the LGN. CONCLUSION: It can be concluded that during early postnatal development of the rats' visual system, light deprivation causes structural and functional changes in LGN. PMID- 22043335 TI - The spectrum of rheumatoid arthritis in patients attending rheumatology clinic in nizwa hospital-oman. AB - OBJECTIVES: To determine the spectrum and expression of rheumatoid arthritis (RA) in patients attending the rheumatology clinic in Nizwa hospital, Oman. METHODS: SUBJECTS AND METHODS: 66 patients fulfilling the American College of Rheumatology (ACR) criteria for the diagnosis of RA were included in the study. The patients were either attending for the first time or were already diagnosed and attending for follow up. The demographic, clinical, laboratory and radiological findings are reported. RESULTS: Of the 66 patients studied, 16 were males and 50 were females. The mean age of patients at onset was 44.5 +/-14.5 years, and the females were younger than males at presentation. 38 (57.57%) were seropositive and two (3.03%) only had rheumatoid nodules. The majority of the patients were considered as class 1 or 2 according to the ACR functional classification. The commonest extra-articular manifestation was anaemia (27.27%) followed by keratoconjuctivitis sicca (24.42%). The upper limb joints were affected more than the lower limbs and the most commonly involved joint was the wrist (81%) followed by the metacarpophalangeal (MCP) (66.66%) joints, the knee (57.57%), ankle (45.45%), elbow (42.42%), shoulder (42.42%), and the proximal interphalangeal (PIP) (36.36%) joints. The main associated diseases were hypertension (21%), ischemic heart disease (13.63%) and diabetes mellitus (9.03%). Systemic features were predominantly morning stiffness (84.5%) and fatigue (45.45%). Reported deaths were due to sepsis and cardiac arrhythmia. Thus 63 (95.45%) of the patients were on conventional disease modifying antirheumatic drugs. CONCLUSIONS: Demographic characteristics were similar to those reported by others, the seropositivity rate and nodular form of the disease was less in the studied patients and the disease seemed milder than that reported in western countries. PMID- 22043336 TI - A Qualitative Study on the Attitudes and Beliefs towards Help Seeking for Emotional Distress in Omani Women and Omani General Practitioners: Implications for Post-Graduate Training. AB - OBJECTIVES: This study aims to explore the attitudes and beliefs of Omani women attending primary health care and Omani general practitioners regarding help seeking behaviour for emotional distress. The study also intends to clarify the understanding of help seeking from both lay and professional perspectives in the context of Omani culture exploring factors related to doctors' training and health care services. METHODS: A qualitative phenomenological study using semi structured interviews was conducted at the Family Medicine Health Care Centre at Sultan Qaboos University Hospital. 20 lay informants (Omani women) and 10 professional informants (Omani family physicians) were interviewed. RESULTS: Two main sets of themes are presented in this study; 1). the original themes, which are presented in the results section and represent the descriptive level of analysis, and 2). the emergent themes are presented in the discussion section and represent the interpretive level of analysis. The original themes are: a) self help, with subthemes including the role of faith, talking and distraction. b) Health care and doctors, with subthemes including: reasons for seeing a doctor, reasons for not seeing a doctor, continuity of care, doctor-patient relationship and time. c) Traditional (folk) medicine. The emergent themes are: a) Talking b) Religious faith c) Cultural beliefs and d) The doctor's role. Cultural and religious beliefs were found to shape the experience of help seeking in the study group. In addition, factors associated with doctor-patient relationship were found to play a major role in determining the help seeking behaviour of women experiencing symptoms related to psychological distress. Professional informants emphasized the role of their training, availability of supporting services, time and continuity of care. The study showed discrepancy between lay and professional informants' beliefs regarding the role of family physicians in managing mental problems. CONCLUSION: This study recommends paying more attention to factors related to cultural beliefs, doctor-patient relationship and family physicians' role when planning health services and residency programs, and when planning research on aspects related to mental health in non-Western cultures. PMID- 22043337 TI - In Vitro Susceptibility Test of Different Clinical Isolates against Ceftriaxone. AB - OBJECTIVES: Because of the prevailing penicillin resistance in microorganisms, broad spectrum cephalosporins are used empirically specially in developing countries. The aim of this study is to determine the susceptibility pattern of different gram positive and gram negative pathogens against third generation cephalosporin-ceftriaxone to explore the existing effectiveness of this antibiotic. METHODS: 180 clinical isolates of different gram positive and gram negative pathogens including P.mirabilis, S. typhi P.aeruginosa, E. coli, S. aureus and Klebsiella were collected from blood and urine samples of in-patients. 30 isolates of all species were tested against each of six brands of ceftriaxone using in vitro sensitivity tests by disc diffusion method (NCCLS criteria). The susceptibility limit was >=21 mm zone of inhibition, while moderately susceptible was considered at 20-14 mm, and those isolates which showed >13 mm or no zone of inhibition were resistant to this antibacterial drug. RESULTS: Ceftriaxone was found most effective against S. aureus. While 96.1% of the isolates showed susceptibility towards ceftriaxone, followed by E. coli (95%), P. aeruginosa (92.7%), K. pneumonia (89.4%) and S. typhi (87.2%). P. mirabilis showed lowest susceptibility amongst all the test organisms (83.8%). CONCLUSION: Ceftriaxone can be used as a drug of choice in infections caused by S. aureus, E. coli, P. aurigenosa, K. pneumonia and S. typhi. However, it should be used with other antimicrobial agents in order to increase its effectiveness against P. mirabilis. PMID- 22043338 TI - Serum leptin and insulin hormone level in recurrent pregnancy loss. AB - OBJECTIVE: To measure serum leptin and insulin levels in women with recurrent pregnancy loss using modified methods of High Performance Liquid Chromatography (HPLC), and to examine their influence on recurrent loss at different pregnancy trimesters. METHODS: A case control study was conducted from, 1 September 2008 to 30 December 2009 in the Obstetric and Gynecological Department-Al-Khadimiya Teaching Hospital. HPLC technique with new modified method was used to estimate serum leptin and insulin hormones in samples of women with recurrent pregnancy loss (patients group, n=64) and healthy pregnant women at the end of the third gestational trimester as a control group (n=51). RESULTS: Both serum leptin and insulin levels were high in women with pregnancy loss in their three trimesters. A significant correlation was found between age (r=0.535, p<0.018) and serum total leptin in women with RPL during the first trimester. Also, a highly significant correlation was found between serum total leptin and insulin in women with RPL during the first, second and third trimesters (r=0.894, r=0.931, and r =0.995) respectively. The number of women who lost their pregnancy during the first trimester was higher than those losing during other trimesters. CONCLUSION: It can be concluded that recurrent pregnancy loss in women at different trimester is associated with endocrine abnormalities where serum leptin and insulin levels increase in a different way compared with normal healthy pregnant women. PMID- 22043339 TI - Blood lead level among fuel station workers. AB - OBJECTIVES: This study aims to determine the level of lead in blood of fuel station workers and in a group of people not occupationally exposed to lead METHODS: 53 control subjects with low risk lead exposure and 45 fuel station workers comprising the study group were included in this study in a period from September 2008 to December 2009. Blood samples were collected and analyzed for each subject by Lead Care Blood Testing System. The average blood lead levels of each group were compared using the independent sample (Mann - Whitney U) test. RESULTS: The median (range) 14.1 (7.5-56) MUg/dl concentration of lead in the blood of fuel stations workers was significantly higher than the median (range) 6.5 (4.0-1.6) MUg/dl concentration of lead in the blood of the control group (p< 0.001).The results obtained also showed that the values of blood lead levels in many workers were higher than action and upper limits acceptable for adults. In fuel station workers, the duration of exposure to leaded fuel was significantly correlated with the blood lead level. CONCLUSIONS: Occupational exposure to lead is prevalent among many fuel station workers in Basrah. A policy action to improve working conditions and to phase out the use of leaded gasoline is recommended. PMID- 22043340 TI - Precipitating and relieving factors of migraine headache in 200 iraqi kurdish patients. AB - OBJECTIVES: To study the precipitating and relieving factors of migraine headache in a group of Iraqi Kurdish patients including the effect of fasting in Ramadan, and to estimate the percentage of family history of migraine. METHODS: A series of 200 migraine cases from different parts of the Kurdistan region in the North of Iraq attending the out-patient Neurology clinic at Rizgary Teaching Hospital and a private Neurology clinic at Erbil City was carried out between October 2007 and May 2008 were reviewed. The precipitating factors and relieving factors for migraine headache were registered and tabulated to be compared with others. Case definition of migraine was based on the International Headache Society (IHS) criteria. RESULTS: 33% of the patients were aged between 30-39 years, while 40.5% of patients experienced their first attack aged between 20-29 years. Stress or psychological upset was the commonest triggering factor (80%), followed by increasing physical activity (68%), change in weather (65.5%), and in relation to fasting (65%). Fasting in Ramadan was a triggering factor for headaches in 65% of patients. However, there was no significant association between the triggering factors with regards to sex difference. Relief of migraine in the studied sample was achieved using NSAIDs in 50% of patients, and sleep (45.5%). Hence, 61% of the study population had positive family history of migraine, 32.5% of them reported maternal history of migraine. CONCLUSION: Psychological upset, stress and excessive physical activity were the commonest triggering factors of migraine headache, while NSAID was the commonest relieving factor of migraine in this population. Family history was present in 61% of migraine patients based mainly from maternal root. PMID- 22043341 TI - Gastroesophageal reflux in children with refractory asthma. AB - OBJECTIVES: To investigate the association between clinical and macroscopic findings of GER and severity of refractory asthma (statistical study). METHODS: A prospective study in a university-based practice of 75 children who were diagnosed with refractory asthma because they exhibited no satisfactory response for at least three months of treatment. Medical history, physical examination, spirometrical measurements and prick skin test were conducted on all patients. Endoscopic and macroscopic evaluations for esophagitis were performed on all patients regardless of the presence of GER symptoms. RESULTS: Endoscopy was done for 75 children with refractory asthma. GER was symptomatic in 65% of all patients with no statistical significance (p>0.05) and the most frequent symptom was abdominal pain (67%). The frequency of these symptoms was 50% in mild asthma, 58% in moderate asthma and 72% in severe asthma with no statistical significance (p>0.05). The frequency of macroscopic esophagitis was 71%, distributed in three asthmatic groups as in order of 75% in mild asthma, 58.3% in moderate asthma and 76.6% in severe asthma (p>0.05). Regarding the relationship between GER and nocturnal attacks or spasmodic cough, the frequency of the latest was 66.7%. The differences have no statistical significance regarding GER symptoms (p>0.05), but they are statistically significant regarding the reflux esophagitis (p<0.05). Also endoscopic reflux was as frequent as76.3% in non allergic patients, and this result is statistically significant (p<0.05). CONCLUSION: In spite of the fact that there was no relationship between the severity of asthma and the symptoms of GER, or its endoscopic findings, the frequency of GER in asthmatic children was higher than its frequency in other children. PMID- 22043342 TI - Vehicular Entrapment and Heat Stroke in Three children: Is it a Form of Child Neglect? AB - The medical records of three children who were entrapped inside vehicles are reviewed and their outcome following the incidents were assessed in this report. The children developed heat stroke following the incidents and survived after several days in coma but with severe cognitive functions impairment. Two of the children were left with hyperactivity and attention deficit, while the third had active epilepsy.Vehicular entrapment heat stroke is one of the preventable brain injuries in children. Several children get entrapped in cars or other vehicles yearly and survivors are left with significant brain damage. The usual cause for brain damage is heat stroke the lesson learned was to never leave children unattended in cars. Therefore, it is essential to double check that doors are locked when leaving children unattended near vehicles. PMID- 22043343 TI - Torsion of an epiploic appendix pretending as acute appendicitis. AB - Torsion of an epiploic appendix is a rare surgical entity. Its unusual symptomatology, wide variation in physical findings and the absence of helpful laboratory and radiological studies makes it very difficult to diagnose pre operatively. This is a report of this rare entity found in a patient upon diagnostic laparoscopy performed for suspected acute appendicitis. PMID- 22043344 TI - Sanjad-Sakati Syndrome in Omani children. AB - Sanjad Sakati Syndrome is an Autosomal Recessive disorder found exclusively in people of Arabian origin. It was first reported from the Kingdom of Saudi Arabia in 1988. This is a report of a family with this rare disease in Oman. The syndrome comprises of congenital hypoparathyroidism, severe growth retardation, low IQ and typical facial features. Supportive treatment in the form of vitamin D and growth hormone is often offered to these children. PMID- 22043345 TI - A case presentation of a large rhinolith. AB - Rhinolith is like a stone formation within the nasal cavity. Although stones rarely form in the nasal cavity, the findings of calcified objects or stones anywhere within the body has long been a subject of interest. Though infrequently observed, nasal concretions can be the source of bad smell from the nose and therefore a social concern for the patient. The salient features of such Rhinoliths and their relevance to clinical practice are discussed and a case of a large Rhinolith is presented in this article. So as to enable the attending clinician to be aware of this forgotten entity, which requires a high index of suspicion. PMID- 22043346 TI - Glycemic control in diabetes. PMID- 22043347 TI - Laparo-endoscopic Assisted Percutaneous Drainage Gastrostomy and Feeding Jejunostomy. PMID- 22043348 TI - Central Nervous System Aspergillosis causing Spinal Cord Compression. PMID- 22043349 TI - Lower cranial nerve palsies. PMID- 22043350 TI - Hypoglycemia and safe driving. PMID- 22043351 TI - Health researchers and policy makers: a need to strengthen relationship. PMID- 22043352 TI - Asthma in children: management issues for family doctors. AB - Asthma is still one of the leading causes of morbidity in children. Despite the improved understanding in the disease pathogenesis and availability of the different classes of drugs, the incidence of emergency visits due to acute exacerbations and admission rates due to frequent and uncontrolled disease is fairly high. Management of bronchial asthma in children is quite different to that of adults. Although there are universal guidelines available for the management of childhood asthma, there is still confusion especially among the family physicians who are largely involved in the management of the children, both in acute exacerbations as well as in long term prevention. This article aims to simplify all the management issues for family physicians in concurrence with the available asthma management guidelines. PMID- 22043353 TI - The effects of subacute exposure of peracetic Acid on lipid peroxidation and hepatic enzymes in wistar rats. AB - OBJECTIVES: This study was undertaken to determine the effect of subacute exposure of peracetic acid on lipid peroxidation and hepatic enzymes in Wistar rats. METHODS: 48 male animals in Treatment Group I, II and III received 0.2%, 2% and 20% peracetic acid daily for 2 and 4 weeks. RESULTS: Serum malondialdehyde increased and Alanine Transaminase and Aspartate Transaminase decreased significantly in groups 2 and 3, compared to the control group. The malondialdehyde, Alanine Transaminase and Aspartate Transaminase with 0.2% and 2% doses of peracetic acid for 2 weeks do not lead to the alteration of malondialdehyde and enzyme activities. CONCLUSION: This study demonstrated that the enhancement of malondialdehyde could provide an oxidative damage induced by disinfectant peroxidation at 20% and 2% doses at 2 and 4 weeks. The consumption of peroxidation with 20% for 2 weeks and 2% for 4 weeks can cause the increase of malondialdehyde and the decrease of enzyme activities, respectively. PMID- 22043354 TI - HER2/neu Immunostaining in Invasive Breast Cancer: Analysis of False Positive Factors. AB - OBJECTIVES: HER2/neu gene amplification by Fluorescent in situ hybridization and protein expression by immunohistochemistry have been used for prognosis and guidance for the treatment of invasive ductal carcinoma of the breast with Trastuzumab. False positive results are a significant problem where immunohistochemistry is exclusively used to test HER2/neu protein over expression. A minority of cases of breast cancer scoring HER2 (3+) by immunohistochemistry using Hercep test may not be associated with amplification of the HER2/neu gene by FISH, a test which is a more specific and sensitive than immunohistochemistry. This study aims to examine the factors contributing to false positive results by immunohistochemistry and subsequently not showing HER2/neu gene amplification by FISH analysis. METHODS: A retrospective analysis of 18 cases (3+) by immunohistochemistry in the pathology laboratory not associated with HER2/neu gene amplification was performed. The histological review of these cases was done, the technical error (i.e staining of blood vessels or benign ducts) and the interpretation errors were evaluated. RESULTS: Polysomy 17 was absent in all the cases studied by FISH analysis. By immunohistochemistry, five of the 18 cases were purely interpretation errors and the remaining were a combination of technical and interpretational errors. CONCLUSION: False positive results related to technical and interpretational errors can be prevented by properly educating the technologist and pathologist to perform high quality immunostains and to render an accurate diagnosis respectively. This issue is of utmost importance as it may have deleterious effects on the selection of therapeutic arsenal in invasive ductal carcinoma of the breast. PMID- 22043355 TI - Safety of simvastatin and goal attainment for low-density lipoprotein cholesterol in sultan qaboos university hospital. AB - OBJECTIVES: Despite the scientific evidence of reducing cardiac events with HMG Co-A reductase inhibitors (statins) therapy in both primary and secondary preventions, these therapies continue to be underutilized in patients receiving convictional care. Simvastatin, a HMG Co-A inhibitor agent, is the most commonly used statin in Sultan Qaboos University Hospital. The aim of this study is to review the safety and the effectiveness of achieving LDL-C targets with Simvastatin according to the NCEP-ATP3 guidelines in patients with different cardiovascular risk categories at Sultan Qaboos University Hospital. METHODS: A retrospective chart review was conducted for 160 patients. Patients were identified by outpatient prescriptions provided by pharmacy department from April 2008 to May 2008. RESULTS: 98% of the patients were prescribed simvastatin 20 mg and only 2% received 40 mg. The mean age of patients was 57 years +/- 12. While 49% of the patients were male and 45% had diabetes mellitus, 50% had cardiovascular disease, 2.5% were smokers, 67% were hypertensive, and 3% had positive family history of coronary artery disease. 75% of patients were classified as high risk, 7% moderate risk and 18% low risk for coronary artery disease. Among all lipid profiles, only LDL-C was changed from baseline with simvastatin treatment in all patients (3.60+/-1.03 to 3.25+/-1.34 mmol/L). LDL-C level at baseline was higher in the high risk group (4.11+/-1.06 mmol/L) compared to low and moderate risk groups (3.68+/-0.89, 3.42+/-1.15) respectively. Achievement of LDL-C goals was achieved in only 43% for high risk, 50% in moderate risk, and 90% in low risk patients. There was no significant increase in liver enzymes and creatinine kinase. CONCLUSION: This study identified that more than half of the high risk patients were not at the target LDL-C goals which place them at a continuous risk of coronary heart disease. More appropriate lipid lowering therapy using more potent statins or combination therapy should be optimized to improve achievement of LDL-C goals according to ATP-III guidelines. PMID- 22043356 TI - Fasting glucose to leptin ratio as a new diagnostic marker in patients with diabetes mellitus. AB - OBJECTIVES: To identify the fasting glucose/leptin ratio as a new simple method for the detection of insulin resistance in Iraqi diabetes mellitus patients, and to examine its usefulness as a new marker for insulin resistance. METHODS: A case control study conducted at the National Diabetes Center, College of Medicine at Al-Mustansiryia University from 1 August 2008 to 30 January 2010. An enzyme spectrophotometric method was used to determine fasting glucose, while HPLC Technique determined leptin and insulin hormones in serum of patients with diabetes mellitus (n=61) and normal healthy subjects as controls (n=63). RESULTS: A positive significant correlation with linear regression equations were found between fasting insulin and fasting leptin hormones, and fasting glucose/insulin and fasting glucose/leptin ratios among the diabetic patient group. While negative, significant correlations were found with linear regression equations between fasting insulin and fasting glucose/insulin ratio, and fasting insulin and fasting glucose/leptin ratio in patients group. Glucopse/leptin ratio had a higher sensitivity compared to glucose/insulin ratio, Quantitative Insulin Sensitivity Check Index and Homeostasis Model Assessment indexes. CONCLUSION: Overall, the glucose/leptin ratio can be used in addition to glucose/insulin ratio, Quantitative Insulin-Sensitivity Check Index, and Homeostasis Model Assessment to accurately assess insulin resistance in subjects with hyperglycemia. PMID- 22043357 TI - Terminalia Arjuna (Roxb.) Modulates Circulatory Antioxidants on 7,12 dimethylbenz(a)anthracene- induced Hamster Buccal Pouch Carcinogenesis. AB - OBJECTIVES: Oral cancer is the fifth most frequent cancer worldwide and India has recorded the highest incidence (40-50%) of oral malignancy. This study is designed to investigate the effect of aqueous extract of Terminalia arjuna bark (TaBet) on circulatory lipid peroxidation and antioxidant status during 7,12 dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. METHODS: Male Syrian golden hamsters painted with 0.5% 7,12 dimethylbenz[a]anthracene on the buccal pouches and developed oral squamous cell carcinoma were included in this study. RESULTS: The enhanced Thiobarbituric acid reactive substances in circulation of tumor-bearing animals was accompanied by a significant decrease in the levels of vitamin C, vitamin E, reduced glutathione, superoxide dismutase, catalase and glutathione peroxidase. Administration of TaBet (500 mg/kg body weight) significantly suppressed DMBA-induced hamster buccal pouch carcinomas, decreased lipid peroxidation and enhanced the levels of antioxidants. CONCLUSION: The chemopreventive potential of TaBet is probably due to its antilipidperoxidative effect or the presence of some potent bioactive chemopreventive principles in the bark of Terminalia arjuna. The results of the present study indicate that T. arjuna may emerge as a putative chemopreventive agent against oral carcinogenesis. PMID- 22043358 TI - Prevalence of uropathogens in diabetic patients and their corresponding resistance pattern: results of a survey conducted at diagnostic centers in dhaka, bangladesh. AB - OBJECTIVES: Urinary tract infection is the second most common clinical indication for empirical antibiotic treatment in primary and secondary health care settings. The incidence of diabetes mellitus throughout the world is increasing strikingly and in the long run, it has some major effects on the genitourinary system which makes diabetic patients more liable to urinary tract infection. This study is designed to reveal the distribution of uropathogens in diabetic patients according to age and sex, and corresponding resistance patterns. METHODS: A six month retrospective review of urine culture assay data from August 2009 to January 2010 from randomly selected 85 patients who suffered from both urinary tract infection and diabetes was conducted. Relevant information was retrieved and analyzed statistically using Microsoft(r) Excel 2002 software. RESULTS: The study showed that females are more vulnerable to pathogenic attack than males throughout a wide age distribution. In terms of pathogenic distribution, Escherichia coli was the highest followed by Streptococcus sp., Acinetobacter, Klebsiella pneumoniae and few others. Though Meropenem showed no resistance with E. coli, Acinetobacter and Klebsiella pneumoniae, in the case of Streptococcus sp. it exhibited resistance of 25%. Amikacin exhibited only 3% resistance with E. coli, whereas no resistance with Acinetobacter and Klebsiella pneumoniae, and most interestingly showed 75% resistance with Streptococcus sp. Gentamicin exhibited no resistance with Acinetobacter while 26.9%, 50% and 87.5% resistance with E. coli, Klebsiella pneumoniae and Streptococcus sp. respectively. Hence, Nitrofurantoin exhibited less resistance 11.9% compared to 12.5% resistance with E. coli and Streptococcus sp. Nitrofurantoin was highly prone to resistance with Acinetobacter and Klebsiella pneumoniae (100%, 50% respectively). Cephalosporins (cephradine, cefixime, ceftriaxone, cefepime etc.) showed moderate resistance (avg. 50%), whereas amoxicillin and ciprofloxacin showed the highest resistance in all these cases. CONCLUSION: Pathogens are mostly resistant to antibiotics including amoxicillin, ciprofloxacin, cephalosporins and nitrofurantoin, with few exceptions including gentamicin, amikacin and meropenem. PMID- 22043359 TI - Serum gamma-glutamyltransferase as Oxidative Stress Marker in Pre-and Postmenopausal Iraqi Women. AB - OBJECTIVES: The primary role of gamma-glutamyltransferase is to metabolize reduced glutathione by assimilating and utilizing precursor amino acids for intracellular glutathione synthesis. The aim of this study is to investigate the exact role of gamma- glutamyltransferase enzyme in the oxidative stress associated with menopause. METHODS: This study was carried out at the Chemistry and Biochemistry department, Al-Nahrain University from October 2009 to January 2010. The study participants were categorized into two groups; premenopausal group (n=17) and postmenopausal group (n=16). Blood specimens were collected from each participant by vein puncture procedure. The gamma-glutamyltransferase enzyme was measured by kinetic spectrophotometric method while glutathione and malondialdehyde were measured by spectrophotometric methods. RESULTS: Serum glutathione levels in pre- and postmenopausal women were 0.62+/-0.17 and 0.47+/ 0.11 mmol/L respectively. Serum gamma-glutamyltransferase levels increased significantly in the postmenopausal women group (p=0.025) compared to the premenopausal women group. Serum malondialdehyde levels were 1.04+/-0.06 and 1.32+/-0.05 MUmol/L in pre- and postmenopausal groups respectively. CONCLUSION: Serum gamma-glutamyltransferase may be considered as an index of oxidative stress associated with menopause. PMID- 22043360 TI - Effect of Treatment with Metformin on Omentin-1, Ghrelin and other Biochemical, Clinical Features in PCOS Patients. AB - OBJECTIVES: Polycystic ovary syndrome is associated with insulin resistance and obesity. Previous studies suggest that metformin by reducing hyperinsulinemia is clinically useful in the treatment of polycystic ovary syndrome. This study's Objective is to observe the role of metformin in omentin1, ghrelin, and other biochemical, clinical features within three months in hyperinsulinemic women with polycystic ovary syndrome. Another aim is to assess the decrease in hyperinsulinemia and body weight by metformin in the population. METHODS: This study was carried out at the Kamal AL-Samarai Hospital between June 2007 and March 2008. 60 women fulfilling the clinical and biochemical criteria for polycystic ovary syndrome and hyperinsulinemia were enrolled. Metformin was started at an oral dose of 850 mg/day for 3 months. Besides Body Mass Index (BMI), Waist Hip Ratio (WHR), serum omentin1, ghrelin, fasting insulin, fasting blood sugar and lipid profile levels were performed. After three months, all these parameters were assessed. Omentin1, ghrelin and insulin were measured by enzyme-linked immunosorbent assay, fasting blood glucose and lipid profile were measured by colorimetric methods. RESULTS: Mean Body Mass Index and Waist Hip Ratio had significantly decreased in the 60 polycystic ovary syndrome patients after three months of Metformin therapy. Serum levels of omentin1, ghrelin and HDL-cholesterol were increased while the total cholesterol/HDL cholesterol ratio was decreased significantly. Serum concentrations of insulin, Homeostatic Model Assessment (HOMA) and HOMA beta-cell % were also decreased significantly, the present study showed a significant increase in omentin1: insulin ratio, omentin1: HOMA ratio and omentin1: HOMA beta-cell% ratio. CONCLUSION: There was a significant an increase in omentin1: insulin ratio, omentin1: HOMA ratio and omentin1: HOMA beta-cell% ratio. These results in the present study are shown the first time, these factors may be useful in following improvements in insulin sensitivity in subjects with polycystic ovary syndrome or obesity treated with insulin sensitizers. Further studies are needed to certify these factors in other populations with these treatment or with other insulin sensitizers or when treated with diet and exercise. PMID- 22043361 TI - Resistance pattern of ciprofloxacin against different pathogens. AB - OBJECTIVES: Ciprofloxacin is a broad-spectrum antibiotic widely prescribed in clinical and hospital settings. The emergence of antimicrobial resistance against effective antibiotics is a global issue. The objective of study is the surveillance of ciprofloxacin against common pathogens. METHODS: To investigate the present status of antimicrobial resistance against ciprofloxacin, five hundred and twenty four clinical isolates of Escherichia coli (30%), Staphylococcus aureus (33%), Salmonella typhi (9%), Klebsiella pneumonia (14%) and Pseudomonas aeruginosa (14%) were collected during study from January, 2008 to February, 2009 from different pathological laboratories running in and out side hospitals located in Karachi, Pakistan. These pathogens were isolated from specimens of both in and out patients. The in-vitro antimicrobial activity of ciprofloxacin was carried out by Disc Diffusion Method (Kirby-Bauer test). RESULTS: Showed that ciprofloxacin is 27.02%, 21.95%, 16.66%, 72.22% and 44.44% resistant to Escherichia coli, Staphylococcus aureus, Salmonella typhi, Klebsiella pneumonia and Pseudomonas aeruginosa respectively. CONCLUSION: It is concluded that these clinical isolates have started developing resistance against ciprofloxacin due to its irrational and inappropriate use. Continuous surveillance is crucial to monitor the antimicrobial resistance among pathogens. PMID- 22043362 TI - Puerperal ovarian vein thrombosis presenting as rt loin pain and hydronephrosis: report of 2 cases. AB - Post-partum ovarian vein thrombosis is an uncommon clinical presentation. 90% of cases present as right loin and right iliac fossa pain, within 10 days of the puerperal period. Two such cases that were referred to the Imaging department as suspected appendicitis/ureteric colic are reported. The findings seen on imaging illustrate the difficulty in the clinical and radiological diagnosis of post partum ovarian vein thrombosis and highlight the need to include it as a differential diagnosis in cases of post partum acute abdomen. Post-partum ovarian vein thrombosis can be accurately diagnosed by appropriate non-invasive investigations to enable early therapy with anti-coagulants and intravenous antibiotics which are the mainstay of treatment. Surgery can be avoided if diagnosis is made early. PMID- 22043363 TI - Long-Term Survival of Gastric Adenocarcinoma without Therapy: Case Report. AB - Planning for treatment of gastric adenocarcinoma in a patient previously treated with partial gastrectomy for primary gastric lymphoma is difficult. Long term survival of advanced gastric adenocarcinoma is poor with therapy and even worse without treatment. The only potentially curative treatment for gastric adenocarcinoma is surgical resection with adequate margins. Palliative surgery ameliorate symptoms in about 50% of patients Chemotherapy may play a lesser role. This report presents a case of gastric adenocarcinoma in a patient who had primary gastric lymphoma treated with partial gastrectomy. The patient is still alive 6 years after diagnosis with no signs of progression despite the fact that no active treatment was given. PMID- 22043364 TI - Transplant renal artery false aneurysm: case report and literature review. AB - This is a case report of a 59 years old male who had a commercial non-related living renal transplantation for his end stage renal insufficiency secondary to adult polycystic kidney disease. He suffered an immediate and early post operative bleeding, which was managed conservatively. He was presented at Sultan Qaboos University Hospital four months after his transplant with abdominal pain, nausea, loss of appetite and a rise in serum creatinine levels. Ultrasonography and angiography have shown a 4 cm false aneurysm of the transplant renal artery at the anastomotic site with the external iliac artery. Surgical exploration with resection of the false aneurysm and reanastomosis of the donor renal artery to the external iliac artery was carried out successfully with preservation of the renal allograft. This is a rare case of an extra-renal false aneurysm at the anastomotic site of the transplant renal artery to the external iliac artery four months after renal allotransplantation. Literature review on the management and outcome of false aneurysms after renal transplant was carried out. PMID- 22043365 TI - Proliferations of scientific medical journals: a burden or a blessing. PMID- 22043366 TI - Substernal thyroid masses. PMID- 22043367 TI - Syncopal attacks and severe abdominal pain. PMID- 22043368 TI - Models of International Emergency Medical Service (EMS) Systems. PMID- 22043369 TI - Gaps in Goals: The history of Goal-setting in Health Care in India. PMID- 22043370 TI - Liquid ventilation. AB - Mammals have lungs to breathe air and they have no gills to breath liquids. When the surface tension at the air-liquid interface of the lung increases, as in acute lung injury, scientists started to think about filling the lung with fluid instead of air to reduce the surface tension and facilitate ventilation. Liquid ventilation (LV) is a technique of mechanical ventilation in which the lungs are insufflated with an oxygenated perfluorochemical liquid rather than an oxygen containing gas mixture. The use of perfluorochemicals, rather than nitrogen, as the inert carrier of oxygen and carbon dioxide offers a number of theoretical advantages for the treatment of acute lung injury. In addition, there are non respiratory applications with expanding potential including pulmonary drug delivery and radiographic imaging. The potential for multiple clinical applications for liquid-assisted ventilation will be clarified and optimized in future. PMID- 22043371 TI - Efficacy of Thrice-daily versus Twice-daily Insulin Regimens on Glycohemoglobin (Hb A1c) in Type 1 Diabetes Mellitus: A Randomized Controlled Trial. AB - OBJECTIVES: To improve glycemic control and prevent late complications, the patient and diabetes team need to adjust insulin therapy. The aim of this study is to evaluate the efficacy of thrice-daily versus twice-daily insulin regimens on HbA1c for type 1 diabetes mellitus by a randomized controlled trial in Hamedan, west of Iran. METHODS: The study included 125 patients under 19 years of age with type 1 diabetes mellitus over a 3-month period. All patients with glycohemoglobin (HbA1c) >=8% were followed prospectively and randomized into two trial and control groups. The control group received conventional two insulin injections per day: a mixture of short-acting (regular) + intermediated acting (NPH) insulins pre-breakfast (twice daily), and the trial group was treated by an extra dose of regular insulin before lunch (three times daily). Main outcome measure was HbA1c at baseline and at the end of 3 months. The mean blood glucose level and number of hypoglycemia were recorded. All patients underwent monthly intervals follow up for assessing their home blood glucose records and insulin adjustment. RESULTS: Overall, 100 patients completed the study protocol. 52% were females, mean +/-SD of age of 12.91 +/- 3.9 years. There were no significant differences in baseline characteristics including age, gender, pubertal stage, adherence to diet, duration of disease and total daily insulin dose (p>0.05). There was a significant decrease individually in both groups in HbA1c level (p<0.05), but there was no significant difference in HbA1c reduction in patients on twice-daily insulin injections and those on thrice-daily insulin injection groups (1.12 +/- 2.12 and 0.98+/-2.1% respectively, p>0.05). CONCLUSION: Compared with twice daily insulin, a therapeutic regimen involving the addition of one dose regular insulin before lunch caused no significant change in the overall glycemic control of patients with type 1 diabetes mellitus. Our results emphasize that further efforts for near normoglycemia should be focused upon education of patients in terms of frequent outpatient visits, more blood glucose monitoring and attention to insulin adjustments. PMID- 22043372 TI - The consequence of delayed fixation on subsequent preservation of urine cells. AB - OBJECTIVES: Degenerative changes caused by delays in urine preservation contribute to false-negative and false-positive interpretation of urothelial disease in cytology. The aim of this study is to assess whether the delay of fixation of urine samples makes any significant difference to urine cytology and morphology, and the limit of acceptability of delay for routine use in the hospital laboratory. METHODS: Three cell collection fluids were evaluated by analyzing the preservation and degeneration of cells in urine samples. In this study, 50 voided urine specimens were taken at random from females complaining of vaginal discharge. Each specimen was divided into three sterile containers. The first was immediately centrifugated and the deposit was smeared onto a cleaned micro slide and immediately fixed into 95% ethyl alcohol for 15 minutes. The remaining two were prepared in the same manner, however, the second after two hours of collection and the third after four hours of collection. The degree of degeneration and thus the preservation were assessed by a table of chosen criteria, then ranked and analyzed using Friedman's nonparametric test, at p=0.05. RESULTS: The results showed a significant difference between the preservation and the delay in urine fixation, p<0.0001. CONCLUSION: Any delay in fixation of urine specimen for cytology affects the preservation of cells, which may result in miss diagnosis. It is recommended that urine samples for cytology should be fixed immediately after collection. PMID- 22043373 TI - Bronchial anthracosis: a potent clue for diagnosis of pulmonary tuberculosis. AB - OBJECTIVES: Occupational exposure to carbon, silica, and quartz particles are predisposing factors for bronchial anthracosis. In some cases anthracosis may be associated with mycobacterium tuberculosis. This study aims to investigate the clinical, radiographic, and bacteriologic findings in bronchial anthracosis patients and its association with tuberculosis. METHODS: This is a prospective study conducted between 1998 and 2001. A total of 919 patients underwent diagnostic bronchoscopy for pulmonary diseases. Of these, 71 patients showed evidence of bronchial anthracosis, 32 (45.8%) males and 39 (54.2%) females, age range, 30-92 years. The distinctive clinical features, nature of bronchoscopic lesions, and radiologic findings were analyzed prospectively and summarized. Bacteriologic studies and results of laboratory examinations were also assessed. RESULTS: Forty-one (57.8%) patients had positive smears or cultures for mycobacterium tuberculosis. Of 71 patients with bronchoscopic evidence of pulmonary diseases, 30 had previous occupational exposure, and 41 stated no previous exposure. Cavitary lesions on chest radiography, positive purified protein derivative tests and high ESR were more prevalent in tuberculous patients than the others. CONCLUSION: Bronchial anthracosis was caused by active or previous tuberculous infection. Detailed examinations for the presence of active tuberculosis should be performed in patients with such bronchoscopic findings in order to prevent the spread of tuberculosis and to avoid unnecessary invasive procedures. PMID- 22043374 TI - Effect of tropicamide and homatropine eye drops on a-scan parameters of the phakic normal eyes. AB - OBJECTIVES: A prospective study to evaluate the changes in A-Scan axial parameters of phakic normal eyes before and after instillation of 1% topical Tropicamide and 2% Homatropine eye drops. METHODS: Anterior chamber depth, lens thickness, vitreous chamber length, and ocular axial length were measured in 76 eyes before and after cycloplegia induced by 1% topical Tropicamide, and in 28 eyes with 2% Homatropine eye drops. RESULTS: Anterior chamber depth demonstrated increase from baseline readings with Tropicamide and Homatropine eye drops, while lens thickness showed decrease from the baseline readings with both eye drops. Effect of both the eye drops on over all axial length and vitreous chamber length is statistically seen, but is clinically negligible and not significant. CONCLUSION: Cycloplegia induced by 1% Tropicamide eye drops and 2% Homatropine eye drops has a significant measurable influence on anterior chamber depth and lens thickness, while vitreous chamber length and overall axial length demonstrated negligible statistical difference on A-Scan parameters of the normal phakic eyes. PMID- 22043375 TI - The awareness and prevalence of metabolic syndrome in medical community of bahawalpur. AB - OBJECTIVES: We investigated the frequency of Metabolic Syndrome and evaluated the level of awareness about this condition in medical community (healthcare workers) of Bahawalpur, Pakistan. METHODS: It was a cross-sectional study. It was carried out over a period of one year (June 2008 to May 2009). The following institutions took part in the study: Bahawal Victoria Hospital, Quaid-e-Azam Medical College, Paramedical and Nursing Schools and Female Jubilee Hospital. A total of one hundred and ninety four (194) Doctors and Paramedics (Nurses and Dispensors) working in the institutions included in study were selected by simple random sampling technique. Demographic, anthropometric, and biochemical data were recorded, lifestyle features were inquired about, and the level of awareness regarding MetS was surveyed. The criteria recommended by the Adult Treatment Panel (ATP) III were used for the diagnosis of MetS. The presence of MetS was evaluated in all (194) subjects. RESULTS: Metabolic syndrome was diagnosed in 29 participants (14.95%), and there was no statistically significant difference between men and women in this respectAt least three criteria of MetS were correctly listed by 36 participants (18.56%), with physicians showing significantly higher awareness levels (p<0.001). The frequency of abdominal obesity was 22.68% and it was significantly higher in males than in females (29.29% vs 14.74%; p<0.001). CONCLUSION: Current study shows that only a minority of medical community are aware of MetS as a clinical entity. Nurses and other paramedics are unaware of the problem. PMID- 22043376 TI - Attitudes towards informed consent: a comparison between surgeons working in saudi arabia and the United kingdom. AB - OBJECTIVES: Changes in legal standing and new guidelines for consent have generated changes in medical culture that doctors must adhere to. This study aims to highlight the differences in the way the surgeons in the two cultures view the informed consent for surgery processes. METHODS: The attitudes towards informed consent of a group of surgeons working in Saudi Arabia (KSA) were compared with those of a similar group working in the United Kingdom (UK), a country with a longer medical history and a more established medico-legal system. RESULTS: The study shows that KSA surgeons tend to view informed consent not only as an ethical and legal obligation but also as a benefit to patients. In addition, KSA surgeons are more likely to adopt a paternalistic attitude during informed consent. They believe that information about harmful risks may dissuade their patients from undergoing the operation and they admit that the amount of information they provide to their patients is significantly influenced by a number of patient and non-patient related factors. CONCLUSION: It is concluded that surgeons in KSA should be more aware of the informed consent guidelines and they should adhere to them. In addition, there is room for the introduction of formal training on informed consent in both countries and for making written information more widely available particularly in KSA. PMID- 22043377 TI - Recurrent laryngeal nerve injury in thyroid surgery. AB - OBJECTIVES: Vocal cord paresis or paralysis due to iatrogenic injury of the recurrent laryngeal nerve (RLNI) is one of the main problems in thyroid surgery. Although many procedures have been introduced to prevent the nerve injury, still the incidence of recurrent laryngeal nerve palsy varies between 1.5-14%. The aim of the present study is to assess the risk factors of recurrent laryngeal nerve injury during thyroid surgery. METHODS: Patients who had thyroid surgery between 1990 and 2005 and were admitted to the surgical department of King Fahd hospital of the University, Al-Khobar, Saudi Arabia were enrolled for this retrospective review, Factors predisposing to recurrent laryngeal nerve injury were evaluated such as pathology of the lesions and the type of operations and identification of recurrent laryngeal nerve intra-operatively. Preoperative and postoperative indirect laryngoscopic examinations were performed for all patients. RESULTS: 340 patients were included in this study. Transient unilateral vocal cord problems occurred in 11 (3.2%) cases, and in 1 (0.3%) case, it became permanent (post Rt. Hemithyroidectomy). Bilateral vocal cord problems occurred in 2 cases (0.58%), but none became permanent. There were significant increases in the incidence of recurrent laryngeal nerve injury in secondary operation (21.7% in secondary vs. 2.8% in primary, p=0.001), total/near total thyroidectomy (7.2% in total vs. 1.9% in subtotal, p=0.024), non-identification of RLN during surgery (7.6% in non identification vs. 2.6% in identification, p=0.039) and in malignant disease (12.8% in malignant vs. 2.9% in benign, p=0.004). However, there was no significant difference in the incidence of recurrent laryngeal nerve injury with regards to gender (4.1% in male vs 3.8% in female, p=0.849). CONCLUSION: The present study showed that thyroid carcinoma, re-operation for recurrent goiter, non-identification of RLN and total thyroidectomy were associated with a significantly increased risk of operative recurrent laryngeal nerve injury. PMID- 22043378 TI - Retrospective Review of Cross Sectional Imaging Findings of Pancreatic Non functional Islet Cell Tumor (NFICT) and its Hepatic Metastases. AB - OBJECTIVES: Review and correlate the computed tomography (CT) imaging features of pancreatic Non Functional Islet Cell Tumors (NFICT) and its hepatic metastases. METHODS: CT examinations of 28 patients with pathologically proven diagnosis of pancreatic NFICT and no clinical symptoms or signs attributed to hormone overproduction, performed at Mallinkrodt Institute of Radiology, Saint Louis, Missouri, USA between March 2002-July 2006, were retrospectively reviewed by two abdominal radiologists. The imaging findings were analyzed and summarized. RESULTS: Pancreatic NFICT size ranged from 1.2-13 cm. The commonest pattern of enhancement was hypervascular and heterogenous enhancement. The spleen was the commonest invaded nearby local structure. The commonest pattern of enhancement noted in the metastatic liver lesions was hypervascular heterogenous enhancement. 26% of the liver metastatic lesions were associated with invasion/encasement of nearby vessels. CONCLUSION: Imaging features of pancreatic NFICT can overlap with other pancreatic neoplasms. Therefore combining the imaging features of pancreatic NFICT and its hepatic metastases helps in narrowing the differential diagnosis. PMID- 22043379 TI - Serotype Prevalence and Penicillin-susceptibility of Streptococcus pneumoniae in Oman. AB - OBJECTIVES: to determine the prevalent serotypes of Streptococcus pneumoniae and the rate of penicillin-nonsusceptibility among pneumococci in Oman. METHODS: Pneumococcal isolates encountered during the period of September 2002 to December 2007 in the Royal Hospital were serotyped. Clinical information as well as the penicillin susceptibility reports were retrieved from the hospital information system and medical records. RESULTS: 120 strains of Streptococcus pneumoniae were isolated of which 85 strains were seroptyped. 20 different serotypes were identified, the most common seroptypes were 9A, 6B, 19F, 14 and 23F. 56% of the strains were not susceptible to pencillin, while 99% of these were susceptible to ceftriaxone. 74.3% and 46.1% of the serotypes are covered by the pneumococcal polysaccharide vaccine and the 7-valent pneumococcal conjugate vaccine respectively. CONCLUSION: Certain few pneumococcal serotypes such as 9A, 6B and 19F are more prevalent in the Omani community than others. More than half of S. pneumoniae are not susceptible to penicillin while the great majority of the strains are susceptible to ceftriaxone. PMID- 22043380 TI - A rare early complication of tracheostomy. AB - A polytrauma patient on ventilator was admitted to ICU with open tracheostomy, GCS 8/15 and unequal pupils. After 10 days, he was weaned from the ventilator. The patient had respiratory problems i.e. expiratory stridor, shortness of breath, dysphonia and dyspnea on closing tracheostomy. It was diagnosed as a case of asthma, and the patient responded to salbutamol nebulization and intravenous steroid therapy. However, after some time, he desaturated and a plan for rapid sequence intubation was made. Endotracheal tube could not be negotiated beyond vocal cords, so an unprepared tracheostomy without proper equipment had to be immediately done by an anesthetist to save the patient's life. CT scan revealed tracheal stenosis. This case demonstrates that patients with a short 15-days history of previous tracheostomy may have tracheal stenosis. PMID- 22043381 TI - Broncho-Oesophageal Fistula (BOF) Secondary to Missing Partial Denture in an Alcoholic in a Low Resource Country. AB - The clinical course of a missing partial denture with secondary BOF in an alcoholic is presented. In the index case we report an exceptional clinical course of a patient who did not ascribe his symptoms to his ''missing'' dentures for several years, the odontologist who replaced an unrecovered denture, and the generalist who administered the barium swallow in an unsuspected BOF. Preoperative optimization of the patient was by blenderized local feeds through a feeding tube gastrostomy and by chest physiotherapy. Extraction of the denture and closure of fistula were done through a right thoracotomy. The importance of a high index of clinical suspicion of BOF in a low resource setting to avoid the morbidity and mortality associated with missing dentures is discussed. Odontologists, caregivers and clinicians must educate patients on the hazards of missing dentures and cases of missing / lost dentures should be adequately investigated / explored in the patient's history and clinical assessment before they are replaced. PMID- 22043382 TI - Tuberculous mastitis presenting as breast abscess. AB - Tuberculous mastitis is a rare clinical entity and usually affects women from the Indian sub-continent and Africa. It often mimics breast carcinoma and pyogenic breast abscess clinically and radiologically, may both co-exist. Routine laboratory investigations are not helpful in its diagnosis. Fine needle aspiration cytology (FNAC) / biopsy are essential for diagnosis and tuberculosis culture when positive may be very useful to guide antimicrobial therapy. Antitubercular drugs in combination with aspiration or surgical drainage are usually associated with an excellent outcome. PMID- 22043383 TI - Extent of surgery for differentiated thyroid cancer: recommended guideline. PMID- 22043384 TI - Should we look for celiac disease in irritable bowel syndrome? PMID- 22043385 TI - 47 year old patient with pseudo-asthma. PMID- 22043386 TI - Pyoderma gangrenosum of abdominal wall: a case report. PMID- 22043387 TI - Fetus in Fetu: A Rare presentation in an Adult female. PMID- 22043388 TI - "Think research" in everyday clinical practice: fostering research culture in health care settings. PMID- 22043389 TI - Food-drug interactions. AB - The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient. PMID- 22043390 TI - Acute Phase Hyperglycemia among Patients Hospitalized with Acute Coronary Syndrome: Prevalence and Prognostic Significance. AB - OBJECTIVES: Regardless of diabetes status, hyperglycemia on arrival for patients presenting with acute coronary syndrome, has been associated with adverse outcomes including death. The aim of this study is to look at the frequency and prognostic significance of acute phase hyperglycemia among patients attending the coronary care unit with acute coronary syndrome over the in-hospital admission days. METHODS: The study included 287 consecutive patients in the Al-Faiha Hospital in Basrah (Southern Iraq) during a one year period from December 2007 to November 2008. Patients were divided into two groups with respect to admission plasma glucose level regardless of their diabetes status (those with admission plasma glucose of <140 mg/dl (7.8 mmol/L) and those equal to or more than that). Acute phase hyperglycemia was defined as a non-fasting glucose level equal to or above 140 mg/dl (7.8 mmol/L) regardless of past history of diabetes. RESULTS: Sixty one point seven percent (177) of patients were admitted with plasma glucose of 3140 mg/dl (7.8 mmol/L). There were no differences were found between both groups regarding the mean age, qualification, and smoking status, but males were predominant in both groups. A family history of diabetes, and hypertension, were more frequent in patients with plasma glucose of 3140 mg/dl (7.8 mmol/L). There were no differences between the two groups regarding past history of ischemic heart disease, stroke, lipid profile, troponin-I levels or type of acute coronary syndrome. Again heart failure was more common in the admission acute phase hyperglycemia group, but there was no difference regarding arrhythmia, stroke, or death. Using logistic regression with heart failure as the dependent variable we found that only the admission acute phase hyperglycemia (OR=2.1344, 95% CI=1.0282 4.4307; p=0.0419) was independently associated with heart failure. While male gender, family history of diabetes mellitus, hypertension and diabetes were not independently associated with heart failure. CONCLUSION: Admission acute phase hyperglycemia of 3140 mg/dl (7.8 mmol/L) was associated with heart failure in this study. PMID- 22043391 TI - De qeurvian tenosynovitis: clinical outcomes of surgical treatment with longitudinal and transverse incision. AB - OBJECTIVES: De Quervain disease is a mechanical tenosynovitis due to inadequacy volume between abductor pollicis longus, extensor pollicis brevis and their tunnel. Treatment methods include immobilization, steroid injections, and operation. For the first time Fritz De Quervain described surgical treatment of this disease. Since then, various ways of treatment have been reported. The purpose of this study is to compare the clinical outcomes of a longitudinal incision with a transverse incision in De Quervain disease. METHODS: This was a randomized controlled clinical trial conducted in three hospitals in Iran, Yazd from March 2003 to September 2008. One hundred-twenty patients with De Quervain disease who did not respond to conservative treatment were operated with two different incisions. The patients were followed for three months to compare the surgical outcomes. RESULTS: During a three month follow-up, a significant difference was shown between the two methods (p=0.03). Results of surgical treatment with longitudinal incision were excellent (only 5 hypertrophic scars), but there were 13 postoperative complaints with transverse incision. CONCLUSION: According to our findings, longitudinal incision in surgical treatment of De Quervain disease is better than transverse incision. PMID- 22043392 TI - Methotrexate treatment of ectopic pregnancy: experience at nizwa hospital with literature review. AB - OBJECTIVES: Ectopic pregnancy occurs when the embryo fails to implant within the uterine cavity. Methotrexate, a folic acid antagonist has been widely used to treat ectopic pregnancy. The aim of this study is to determine the efficacy of methotrexate treatment for ectopic pregnancies in our settings which will in-turn help us reduce maternal mortality and morbidity. METHODS: This was a retrospective review of 60 cases of ectopic pregnancy treated with single dose methotrexate in Nizwa hospital, Oman. Demographic data, clinical presentation, treatment progress, outcome, side effects and future fertility follow up were analysed using a computer database. Selection criteria included hemodynamically stable women with beta-hcg level of <=5000 mIU/ml, adnexal mass <=4 cm, absent cardiac activity and hemoperitoneum less than 100 ml. Human chorionic gonadotrophin (hcg) assay and clinical presentation were used to determine cases which warranted surgical intervention. RESULTS: The success rate of single dose methotrexate therapy in our study was 65% (n=39) and 35% (n=21) required surgical intervention compared to reported success rate of 67-100% published in various studies. Careful selection of cases and confining strictly to the criteria improved the success rate from 40% to 60% in five and half years of the study. The mean average time of resolution of ectopic pregnancy was 32 days for a single dose and 58 days for repeat second or third doses. Eight cases of pregnancy of unknown location were treated successfully with Methotrexate. No major side effects were noted. A successful fertility outcome of 30% in the first year followed by 13.3% in the subsequent second year with a secondary infertility rate of 11.6% was observed in this study. CONCLUSION: Methotrexate treatment of ectopic pregnancies is safe and effective with no major side effects. Intramuscular methotrexate has the advantage of tubal conservation and saves patients from requiring surgery. It is easier to administer than intraoperative route, which is by laparoscopy and needs expertise. Our study showed single dose methotrexate to be an effective treatment option for selected patients with unruptured tubal ectopic pregnancy. PMID- 22043393 TI - Impact of Implementing Grading Fine Needle Aspiration Cytology in Diagnosis of Breast Cancer amongst Sudanese Women. AB - OBJECTIVES: This study estimated the merit of employment of Grading Fine Needle Aspiration Cytology (GFNAC) in the assessment of breast lumps, compared to conventional Conventional Fine Needle Aspiration Cytology (CFNAC). METHODS: Seventy-five women with breast lumps were referred to the surgical unit at Khartoum Teaching Hospital. Fine Needle Aspiration (FNA) materials were obtained for cytology and biopsies from the same patients for histopathology. Cytological materials were assessed using two diagnostic systems (GFNAC and CFNAC) without prior knowledge of the histopathologic diagnosis. RESULTS: Of the 75 patients studied, 40 (53.3%) were diagnosed as having breast cancer by Histopathology and the remaining 35 (46.7%) were diagnosed with benign lesions. Of the 40 positive cases, 35 (87.5%) and 28 (70%) were found positive by CFNAC and GFNAC respectively. Of the 35 negative cases, 33 (94.3%) and 35(100%) were found negative by CFAC and GFAC correspondingly. CONCLUSION: The obtained Specificity of 94.3% and 100% in addition to sensitivity of 87.5%, 70% were credited for CFNAC and GFNAC systems respectively. Therefore, it is recommended to merge GFNAC as a supplementary to CFNAC for the diagnosis of breast cancer. PMID- 22043394 TI - Hypoglycemic Effect of Calotropis gigantea Linn. Leaves and Flowers in Streptozotocin-Induced Diabetic Rats. AB - OBJECTIVES: To evaluate the hypoglycemic and anti-diabetic activity of chloroform extract of Calotropis gigantea leaves and flowers in normal rats and streptozotocin induced diabetes. METHODS: The hypoglycemic activity in normal rats was carried out by treatment using chloroform extract of Calotropis gigantea leaf and flower 10, 20 and 50 mg/kg, orally. The oral glucose tolerance test was carried out by administering glucose (2 g/kg, p.o), to non-diabetic rats treated with leaf and flowers extracts at oral doses 10, 20 and 50 mg/kg, p.o and glibenclamide 10 mg/kg. The serum glucose was then measured at 0, 1.5, 3 and 5 hr after administration of extracts/drug. Streptozotocin-induced diabetic rats were administered the same doses of leaf and flower extracts, and standard drugs glibenclamide was given to the normal rats or 0.5 ml of 5% Tween-80, for 27 days. The blood sample from all groups collected by retro-orbital puncture on 7, 14, 21 and 27th days after administration of the extracts/drug and used for the estimation of serum glucose levels using the glucose kit. RESULTS: The Calotropis gigantea leaves and flowers extracts were effective in lowering serum glucose levels in normal rats. Improvement in oral glucose tolerance was also registered by treatment with Calotropis gigantean. The administration of leaf and flower extracts to streptozotocin-induced diabetic rats showed a significant reduction in serum glucose levels. CONCLUSION: It is concluded that chloroform extracts of Calotropis gigantea leaves and flowers have significant anti-diabetic activity. PMID- 22043395 TI - A study measuring the effect of high serum triglyceride and cholesterol on glucose elevation in human serum. AB - OBJECTIVES: The purpose of this study is to further confirm the results documented in previous studies and to test the hypothesis of the presence of any correlation and if found, the regression nature of such correlation between triglyceride and glucose levels in one hand and cholesterol and glucose levels in the other hand. METHODS: Samples were collected between March and August 2009 from 438 of both males and females from two patient groups; a) non-diabetic patients, b) non-insulin dependent type II diabetic patients. The patients' serum glucose; cholesterol and triglyceride were simultaneously determined. A comparison study was conducted on the effect of the elevated level of each of the parameters (Cholesterol and Triglyceride) on glucose elevation. RESULTS: The results showed that there was a significant difference in the number of cases with high glucose values >110 mg/dl among the three different study groups. There was a significant difference in the number of cases with glucose values >110 mg/dl between the two different study groups; 1) triglyceride <151 mg/dl and cholesterol >201 mg/dl, 2) triglyceride >151 mg/dl and cholesterol>201 mg/dl. CONCLUSION: The elevation in triglyceride but not cholesterol has the same effect of both triglyceride and cholesterol elevation together on the association with increasing levels of high glucose in blood. PMID- 22043396 TI - Measles in a tertiary institution in bida, niger state, Nigeria: prevalence, immunization status and mortality pattern. AB - OBJECTIVES: Measles is a highly infectious immunizable disease with potential for eradication but is still responsible for high mortality among children, particularly in developing nations like Nigeria. This study aims to determine the hospital based prevalence of measles, describe the vaccination status of children managed for measles at the Federal Medical Centre, Bida, Niger state and to identify the parental disposition to measles vaccination. METHODS: This is a cross-sectional study carried out over a period of 18 months beginning from July 2007. All children with a diagnosis of measles made clinically and reinforced with serological test in the WHO Measles, Rubella and Yellow Fever laboratory in Maitama District Hospital, Abuja were recruited. Informed consent was obtained from the parents/care givers. Structured questionnaire was used to obtain information and data analysis was by SPSS version 15. RESULTS: One hundred and nine children were managed for measles, constituting 8% of total admission over the study period. The male to female ratio was 1.2:1. Of the 109 children with measles, 90 (82%) did not receive measles vaccination. Eighty-eight (80%) of the parents or guardian felt vaccination was bad for various reasons. Of the 23 (21.1%) children whose parents or guardians were positively disposed to vaccination, one death was recorded while the remaining seven deaths were recorded among children whose parents were negatively disposed to vaccination. All the deaths were in the non-vaccinated group below 2 years of age. CONCLUSION: Measles is still a major health burden in our community. The majority of affected children were not vaccinated due to negative parental disposition. Continuous health education is required for change the disposition of the parents/guardian and improve vaccination coverage to minimize measles associated morbidity and mortality. PMID- 22043397 TI - Vascular endothelial growth factor in bronchoalveolar lavage fluid in sulfur mustard exposed lung patients. AB - OBJECTIVES: To determine the levels of vascular endothelial growth factor isoform consisting of 165 amino acids (VEGF165) in Bronchoalveolar Lavage Fluid from Mustard Exposed Patients. METHODS: Bronchoscopy with Bronchoalveolar Lavage was performed on sulphur mustard exposed patients. A total of 39 patients with documented exposure to Sulfur Mustard during the Iran-Iraq war participated in this study, of which 38 patients were males and one patient was female. RESULTS: The mean+/-SD age of patients was 41 +/- 6.6 years. The mean time after exposure to sulfur mustard was 19 +/-1.7 years. Eighteen patients had concomitant war injuries but they were not related to the respiratory system. While Twenty-two patients had a history of submassive persistent hemoptysis. There was no case with massive hemoptysis. Most of the patients had small airway obstruction (FEV1/FVC% = 78.14 +/- 9.76 and FEV1% =82.79+/-18.23). Twenty-three patients had significant air trapping in the chest. High Resolution Computed Tomography was compatible with BOS. VEGF165 concentrations in BALF were 36.87 +/- 34.68 pg/ml. When corrected to total protein of Bronchoalveolar Lavage Fluid (BALF) it was 0.76 +/- 0.70 pg/mg. BALF of VEGF did not correlate with hemoptysis or air trapping in chest HRCT. Thus, there was also no correlation between level of VEGF165 in BALF and any of PFT indexes (FVC, FEV1, MMEF or PEF). CONCLUSIONS: Although VEGF is one of the cytokines which has an important role in chronic pulmonary disorders, it seems that it has no essential role in the severity of Mustard Lung Disease. PMID- 22043398 TI - Tonsillo-Styloidectomy for Eagle's Syndrome: A Review of 15 Cases in KVG Medical College Sullia. AB - Elongated styloid process causing Eagle's Syndrome is a rare clinical entity and the diagnosis is often difficult as a result of its vague symptomatology. However, palpation of tonsillar fossa with radiological demonstration of the elongated styloid process confirms the diagnosis. This is a report of a retrospective study conducted at the KVG Medical College, Hospital, Sullia, Karnataka, India where 15 patients who were surgically treated for Eagle's syndrome in the ENT department were retrospectively studied. Fourteen patients became symptom free after surgery within three months of follow up. Tonsillo styloidectomy is the treatment of choice for Eagle's syndrome with a high success rate. PMID- 22043399 TI - An unusual cause of gastrointestinal obstruction: bezoar. AB - Bezoars are concretions of swallowed hair, fruit vegetable fibers, and similar substances found in the alimentary canal. The first description of a postmortem human bezoar was by Swain in 1854. Although the prevalence of bezoars in humans is low, an absence of treatment has been associated with mortality rates as high as 30%, primarily because of gastrointestinal bleeding, destruction, or perforation. PMID- 22043400 TI - Hiccup: an extremely rare presentation of thyrotoxicosis of graves' disease. AB - Persistent hiccup is a rare but potentially severe condition that can be symptomatic of a variety of diseases or idiopathic. Most episodes last only a few minutes and are self-limited, but hiccup can get persistent and become a real problem for physician and patient alike. The center of hiccup may be activated by a great variety of stimuli travelling along different nerve pathways and bring different effecter responses. We report a case of persistent hiccup as a presentation of impending thyroid storm of Graves' disease. Though the condition is rare, clinicians should remain alert to the possibility of this diagnosis. PMID- 22043401 TI - Audit of inpatient management and outcome of limb fractures in children. PMID- 22043402 TI - The Role of Pre-emptive Control of Vascular Pedicle in Laparoscopic Splenectomy: An Experience with 19 Consecutive Patients. PMID- 22043403 TI - Diabetic women with Fever and right flank pain. PMID- 22043404 TI - Reproductive health in iran: international conference on population and development goals. PMID- 22043405 TI - A call for a quite debate on the future of genetics research. PMID- 22043406 TI - Patient medication adherence: measures in daily practice. AB - Adherence to therapies is a primary determinant of treatment success. Failure to adherence is a serious problem which not only affects the patient but also the health care system. Medication non adherence in patients leads to substantial worsening of disease, death and increased health care costs. A variety of factors are likely to affect adherence. Barriers to adherence could be addressed as patient, provider and health system factors, with interactions among them. Identifying specific barriers for each patient and adopting suitable techniques to overcome them will be necessary to improve medication adherence. Health care professionals such as physicians, pharmacists and nurses have significant role in their daily practice to improve patient medication adherence. PMID- 22043407 TI - Quantitative and Qualitative Analysis of PubMed-Indexed Biomedical Publications in Oman from years 2005-2009. AB - OBJECTIVES: Research activities are promoted at the government and the institutional levels in Oman. However, the quantity and quality of research conducted in various institutes of Oman has not been measured. Therefore, this study was conducted to analyze the quantity and quality of biomedical publications emanating from Oman over the last five years (2005-2009). METHODS: Data regarding the biomedical publications of Omani origin published from January 2005 to December 2009 were retrieved from Pubmed. All abstracts were manually checked to exclude false retrievals. The journal impact factor (IF) for 2008 was applied for every publication. Full-length original articles, review articles and publications mentioning new research methods/new technique were assigned full IF of the journal. However, half of the journal IF were assigned to correspondences/commentaries, case reports/series and short communications. RESULTS: Of biomedical publications, 752 were retrieved from Pubmed and 519 publications were included for final analysis after excluding false positives. The number of biomedical publications steadily increased over the last five years, but it was not statistically significant. Original research articles constituted more than half (54.3%) of all the publications, followed by case reports/series (30.1%). Sultan Qaboos University (SQU) contributed more than half of the biomedical publications (51.5%), followed by the Ministry of Health (MoH), which contributed 38% of the publications. Interestingly, the mean IF of the publications was not significantly different throughout the years. CONCLUSIONS: The number of publications emanating from Oman increased over the last five years; however, the quality of research has not improved. Furthermore, the research in Oman is mainly conducted by the government-run institutions and there is hardly any contribution from the private institutions. PMID- 22043408 TI - In Vitro alpha-Amylase Inhibition and Antioxidant Activities of Methanolic Extract of Amaranthus Caudatus Linn. AB - OBJECTIVES: The present study was aimed to investigate the alpha-amylase inhibition and antioxidant activities of methanolic extract of Amaranthus caudatus Linn (MeAc). METHODS: Methanolic extract of Amaranthus caudatus was screened for alpha-amylase inhibition activity by CNPG3 method (2-chloro-p nitrophenyl-alpha-D-maltotrioside) and antioxidant activity was evaluated by 1,1 diphenyl-2-picryl-hydrazile (DPPH) free radical scavenging, superoxide dismutase (SOD) scavenging, hydroxyl free radical scavenging, nitric oxide (NO) radical scavenging, and 2.2'-azinobis-3-ethylbenzothiazole-6-sulfonic acid (ABTS) radical scavenging assays. MeAc was also screened for non enzymatic hemoglycosylation. RESULTS: The methanolic extract of Amaranthus caudatus showed potent alpha amylase inhibition activity (IC(50) 19.233 ug/ml). MeAc showed significant antioxidant activity in all the in vitro antioxidant models. Furthermore, the MeAc was found to be extremely effective in scavenging ABTS radical activity (IC(50) 48.75+/-1.1 ug/ml) when compared to DPPH (IC(50) 77.5+/-0.4 ug/ml), SOD (IC(50) 62.5+/-2.1 ug/ml), hydroxyl (IC(50) 88.50+/-1.8 ug/ml) and NO (IC(50) 67.5+/-2.2 ug/ml) scavenging activity. CONCLUSIONS: The methanolic extract of A. caudatus showed potent alpha-amylase inhibition and antioxidant activities. PMID- 22043409 TI - Laparoscopic management of malfunctioning peritoneal dialysis catheters. AB - OBJECTIVES: Continuous ambulatory peritoneal dialysis (CAPD) is an established alternative method to hemodialysis for treating end-stage renal disease patients. Malfunction of the peritoneal catheter is a frequent complication in peritoneal dialysis (PD). Laparoscopy is a minimal invasive technique that allows rescue therapy of malfunctioning catheters and consecutive immediate resumption of PD. The purpose of this study is to present our experiences with laparoscopic repair of peritoneal catheter dysfunction METHODS: Between April 2006 and March 2010, 21 cases of laparoscopic interventions were performed for the salvage of malfunctioning CAPD catheter. Two trocars (5 mm) were used. Recorded data included patient demographics, catheter implantation method, date of malfunction, cause of dysfunction, procedure performed and complications. RESULTS: The primary etiology of dysfunction was omentum and/or small bowel wrapping with adhesions in fifteen cases, malpositioning in four cases, and tunnel infection in the remaining two cases. Adhesiolysis was performed in cases with adhesions. In the cases with malpositioning but no adhesions, the catheters were repositioned in the pelvic cavity. Two catheters had to be withdrawn and exchanged because of infection. There were no mechanical or infection problems. The overall success rate of catheter function (>30 days after laparoscopy) was 100%, except for two cases in which the catheters had to be removed. CONCLUSION: Laparoscopy is a safe, highly effective and successful method for the evaluation and management of peritoneal dialysis catheter dysfunction. PMID- 22043410 TI - Proportion of Urinary Schistosomiasis among HIV-Infected Subjects in Benin City, Nigeria. AB - OBJECTIVES: This study aimed to determine the prevalence of urinary schistosomiasis, and the effect of CD4(+) T cell counts and demographics on its prevalence among HIV-positive patients in Benin City, Nigeria. METHODS: Urine and blood samples were collected from 2000 HIV-positive subjects. A wet preparation of the urine deposit was examined microscopically to identify ova of Schistosoma haematobium. The blood specimens were analyzed using the flow cytometry for CD4 (+) T-lymphocyte count. RESULTS: An overall prevalence rate of 0.3% was reported. Gender and CD4 count <200 cells/uL did not affect the prevalence of urinary schistosomiasis, while HIV patients that were single had significantly higher prevalence of urinary schistosomiasis (p=0.002). CONCLUSION: The prevalence of urinary schistosomiasis among HIV patients in Benin City is low. CD4(+) count did not affect the prevalence of urinary schistosomiasis. PMID- 22043411 TI - Management of adenomyosis in subfertile women and pregnancy outcome. AB - OBJECTIVES: To assess the outcome of treatment with only gonadotropin releasing hormone agonists (Gn-RHa) versus combined conservative surgery and Gn-RHa therapy in the management of sub-fertile patients with symptomatic uterine adenomyosis. METHODS: A retrospective study of the two treatment modalities allocated to 40 sub-fertile patients with pathology-proven adenomyosis over a period of eight years was undertaken at the Obstetrics and Gynecology department, King Fahad Hospital, Dammam University, Saudi Arabia. Twenty-two patients (Group A) were treated with Gn-RHa alone, and 18 patients (Group B) received combined conservative surgery with Gn-RHa therapy. After completion of six courses of Gn RHa injections, there was a 3-year follow up period for all patients. Treatment outcome included relief of symptoms, pregnancy rate and successful deliveries, which were compared between the two groups. RESULTS: The patients in group A were younger in age, had lower CA-125 levels and shorter infertile years than Group B. Three (13.6%) spontaneous pregnancies resulted upto 18 months of stopping Gn-RHa in group A, while 8 (44.4%) pregnancies resulted upto 36 months in group B patients, which was statistically significant (p=0.0393). Term delivery occurred normally in one (4.5%) Group A patient, while 6 (33.3%) patients in Group B had cesarean section at term (p=0.0328). CONCLUSION: Combined conservative surgery and Gn-RHa may provide effective symptom relief, better reproductive performance in subfertile patients with uterine adenomyosis and longer period of pregnancy prospects after treatment than patients who recieved Gn-RHa alone. Due to the nature of this study, a well conducted randomized trial is needed in the future to assess the benefits of the two treatment modalities. PMID- 22043412 TI - Prevalence of Intestinal Parasites among Patients of Al-Noor Specialist Hospital, Makkah, Saudi Arabia. AB - OBJECTIVES: To determine the prevalence of intestinal parasites among patients of a tertiary care hospital. METHODS: A total of 12,054 samples received from the outpatient as well as inpatient departments from January 1, 2004 to December 31, 2009 in Al-Noor Specialist Hospital, Makkah, Saudi Arabia. Stool examinations were performed by direct method and concentrated Techniques for all patients. RESULTS: Overall, the prevalence of intestinal parasites was 6.2% (740 cases). Majority of patients were infected by Entamoeba histolytica (4.7%) followed by Giardia lamblia (1.3%), while Ankylostoma duodenal (0.02%) exhibited the minimum prevalence. Parasitic infections were more frequent in non-Saudis than Saudis patients (7.1% vs. 5.8%; p<0.05). There was no significant difference between males and females regarding parasitic infections, with a female:male ratio of 1:1.08. There was a higher prevalence in patients under five years of age (9.1%), followed by patients aged 5-14 years (7.5%). CONCLUSION: The notable finding from this study is the high prevalence of E. histolytica. Overall, parasitic infections were more prevalent in patients under five years of age and in non Saudi nationals. PMID- 22043413 TI - In vitro activity of vancomycin and teicoplanin against coagulase negative staphylococci. AB - OBJECTIVES: With the increase in nosocomial infections caused by coagulase negative staphylococci (CNS), laboratory diagnosis of CNS with reduced susceptibility to glycopeptides (vancomycin and teicoplanin) has become important. This study was designed to determine the glycopeptide susceptibility of clinical isolates of methicillin resistant coagulase negative staphylococci (MRCNS) at the department of microbiology, government medical college and hospital, Amritsar, India. METHODS: A total of 250 CNS isolated from various clinical specimens were speciated and their methicillin resistance was detected by studying the minimum inhibitory concentration (MIC) of oxacillin by macrobroth dilution method. Glycopeptide susceptibility of 130 methicillin resistant strains obtained was determined for vancomycin by vancomycin screen agar test, MIC of vancomycin by macrobroth dilution/and E test. Teicoplanin susceptibility was determined using teicoplanin disc diffusion test and MIC was determined by macrobroth dilution method. RESULTS: All the MRCNS isolates were found to be susceptible to vancomycin and teicoplanin. MIC of vancomycin ranged between <=0.5 ug/ml to 1 ug/ml and of teicoplanin from <=0.5 ug/ml to 2ug/ml. CONCLUSION: Continuous monitoring of MIC of vancomycin in MRCNS is required to prevent the emergence of vancomycin resistance in these multidrug resistant organisms. PMID- 22043414 TI - Risk Factors for Type 1 Diabetes Mellitus among Children and Adolescents in Basrah. AB - OBJECTIVES: Environmental factors play an important role in the pathogenesis of type 1 diabetes mellitus, many of these factors have been uncovered despite much research. A case-control study was carried out to determine the potential maternal, neonatal and early childhood risk factors for type 1 diabetes mellitus in children and adolescents in Basrah. METHODS: A total of 96 diabetic patients who have been admitted to the pediatric wards at 3 main hospitals in Basrah, and those who have visited primary health care centers over the period from the 4(th) of November 2006 to the end of May 2007 were recruited. In addition, 299 non diabetic children were included, their age ranged from 18 months to 17 years. RESULTS: Family history of type 1 diabetes mellitus and thyroid diseases in first and second degree relatives was found to be an independent risk factor for type 1 diabetes mellitus, (p<0.001). Regarding maternal habits and illnesses during pregnancy, the study has revealed that tea drinking during pregnancy is a risk factor for type 1 diabetes mellitus in their offspring, (p<0.05). In addition, maternal pre-eclampsia and infections were found to be significant risk factor for type 1 diabetes mellitus, (p<0.001). Neonatal infections, eczema and rhinitis during infancy were also significantly associated with development of type 1 diabetes mellitus. Moreover, the results revealed that duration of <6 months breast feeding is an important trigger of type 1 diabetes mellitus. CONCLUSION: Exposure to environmental risk factors during pregnancy (tea drinking, pre eclampsia, and infectious diseases), neonatal period (respiratory distress, jaundice and infections) and early infancy are thought to play an important role in triggering the immune process leading to B-cell destruction and the development of type 1 diabetes mellitus. PMID- 22043415 TI - Thanatophoric dysplasia: a rare entity. AB - Thanatophoric dysplasia is the lethal skeletal dysplasia characterized by marked underdevelopment of the skeleton and short-limb dwarfism. The child will be having a short neck, narrow thoracic cage and protuberant abdomen. Other anatomical features include a relatively enlarged head with frontal bossing, prominent eyes, hypertelorism and the depressed nasal bridge. The diagnosis is usually made with the ultrasonography in the second trimester. In this study we report a case of this rare entity with emphasis on its anatomical features, abnormalities and clinical profile with relevant review of literature. PMID- 22043416 TI - Dysgerminoma with pregnancy and viable baby: a case report. AB - Dysgerminomas are the most common of primitive germ cell tumors of the ovary, accounting for 1-5% of all ovarian malignancies. The reproductive age group females are most commonly affected, thereby causing problems in conception and if pregnancy occurs, it leads to feto-maternal compromise. It is extremely rare to have a successful natural pregnancy, with viable child birth with a coexisting dysgerminoma, without any assisted reproductive interventions. We hereby report a case of successful spontaneous natural pregnancy in a primi gravida, associated with dysgerminoma, with no feto-maternal compromise. PMID- 22043417 TI - Vitamin d toxicity in adults: a case series from an area with endemic hypovitaminosis d. AB - Vitamin D deficiency state is endemic to the Kashmir valley of the Indian subcontinent. Physicians often treat patients with high doses of vitamin D for various ailments and on occasion the prescribed doses far exceed the requirements of the patients. Ten cases of hypercalcemia due to vitamin D intoxication are presented with features of vomiting, polyuria, polydipsia, encephalopathy and renal dysfunction. All the patients had demonstrable hypercalcemia and vitamin D levels were high in nine of the 10 cases. The patients had received high doses of vitamin D and no other cause of hypercalcemia was identified. Treatment of hypercalcemia resulted in clinical recovery in nine cases. We conclude that hypervitaminosis D must be considered in the differential diagnosis of patients with hypercalcemia in endemically vitamin D deficient areas. A careful history and appropriate biochemical investigation will unravel the diagnosis in most of the cases. PMID- 22043418 TI - General physicians and prescribing pattern in isfahan, iran. PMID- 22043419 TI - Arsenic poisoning in bangladesh. PMID- 22043420 TI - Cystic pelvic lesion. PMID- 22043421 TI - Diagnostic difficulties in differentiating sarcoidosis from tuberculosis. PMID- 22043422 TI - An insight: medical tourism, local and international perspective. PMID- 22043423 TI - Objective structured clinical examination: the assessment of choice. AB - The Objective Structured Clinical Examination is a versatile multipurpose evaluative tool that can be utilized to assess health care professionals in a clinical setting. It assesses competency, based on objective testing through direct observation. It is precise, objective, and reproducible allowing uniform testing of students for a wide range of clinical skills. Unlike the traditional clinical exam, the OSCE could evaluate areas most critical to performance of health care professionals such as communication skills and ability to handle unpredictable patient behavior. PMID- 22043424 TI - Tropical cyclone gonu: number of patients and pattern of illnesses in the primary health centers in a'seeb area, muscat, sultanate of oman. AB - OBJECTIVES: On June 6(th) 2007, a tropical Cyclone Gonu striked the coastline of Oman. The purpose of this study is to compare number of patients and pattern of illnesses between disaster (June 2007) and peace times (June 2006/2008). METHODS: Descriptive comparative analysis of all patients who visited primary health centers in Wilayat A'Seeb during the index days. Electronic database collected from the Health Centers (HC) were grouped into four groups; infection-related, trauma-related, acute non trauma-related, and miscellaneous group. Data were analyzed to find difference of patient influx and disease patterns between disaster and peace times. RESULTS: HC visits during the index days decreased from 9006 in 2006 to 8687 in 2007 then increased to 8786 in 2008. Neither between years variation nor between disaster and peace times difference was found to be statistically significant. The proportion of patient visited the HC due to infection-related illnesses changed from 30% in 2006, 31% in 2007, and 24% in 2008 (p<0.0001). The proportion of patients visited the HC due to trauma-related illnesses had changed from 4% in 2006, to 6.7% in 2007, and to 4.4% in 2008. (p<0.0001). Proportions for acute non trauma-related visits were 27% in 2006, 24% in 2007, and 23% in 2008 (p<0.0001). Miscellaneous group accounted for 38% in 2006, 37% in 2007, and 47% in 2008 (p<0.0001). CONCLUSION: Tropical Cyclone Gonu caused statistically significant increase in percentages of infectious and trauma related visits. The overall ratios of total visits did not differ from peace times. PMID- 22043425 TI - Immunohistochemical Expression of ki-67 and p53 in Colorectal Adenomas: A Clinicopathological Study. AB - OBJECTIVES: To evaluate the significance of P53 and Ki-67 expression as immunohistochemical markers in early detection of premalignant changes in different types of colorectal adenomas. Also, to correlate immunohistochemical expression of the two markers with different clinicopathological parameters including; age, and sex of the patient, type, site, size and grade of dysplasia of colorectal adenomas. METHODS: Forty-seven polypectomy specimens of colorectal adenomas were retrieved from the archival materials of the Gastrointestinal and Hepatic Diseases Teaching Hospital in Baghdad from 2009 - 2010. Four um section specimens were stained by immunohistochemical technique with Ki-67 and P53 tumor markers. P-values <0.05 were considered statistically significant. RESULTS: Immunohistochemical expressions of Ki-67 and P53 had a significant correlation with the size and grade of dysplasia in colorectal adenomas. However, there was no significant correlation among the immunohistochemical expression of Ki-67 and P53 with the age and gender of the patient, and the type and site of colorectal adenomas. There was no significant correlation between Ki-67 and P53 expressions in colorectal adenomas. Villous adenomas of colorectum showed a significant correlation with the grade of dysplasia, while there was no significant correlation between size and site of colorectal adenoma with the grade of dysplasia. CONCLUSION: High grade dysplasia with significant positive immunohistochemical markers of Ki-67 and P53 could be valuable parameters for selecting from the total colorectal adenoma population, those most deserving of close surveillance in follow-up cancer prevention programs. It is closely linked with increasing age particularly in patients with a large size adenoma of villous component in their histology. PMID- 22043426 TI - Prevalence of Depressive Symptoms among University Students in Oman. AB - OBJECTIVES: To study the prevalence of depressive symptoms and its association with gender, academic year, and college among university students in Oman. METHODS: A cross-sectional study was conducted among Omani students attending the students' clinic of the Sultan Qaboos University (SQU). A systematic sampling of students, males and females, from different colleges, who visited the clinic during the study period, was carried out. The self-administered Patient Health Questionnaire (PHQ-9) was used to screen for propensity to depression. RESULTS: A total of 481 students participated in the study (243 males and 238 females). Overall, 133 (27.7%) of the participants (66 males and 67 females) had depression of various grades based on the PHQ-9 diagnostic criteria using a cut point of more than 11. Depression score at the cut point of 11 was not statistically associated with gender, college and the academic year. CONCLUSION: Tendency for depression might be a common health problem among college students in Oman attending primary health care facilities. Further research on socio-demographic characteristics and the effect of depression on the academic performance is needed. PMID- 22043427 TI - Bloodstream Bacterial Pathogens and their Antibiotic Resistance Pattern in Dhahira Region, Oman. AB - OBJECTIVES: To describe the epidemiological, clinical, microbiological characteristics and antimicrobial resistance pattern of Bloodstream infections in Dhahira region, Oman. METHODS: Clinical data was collected from all patients with positive blood cultures for two years period. Standard laboratory methods were used for blood culture. Antibiotic sensitivity was tested using Kirby-Bauer disc diffusion method. RESULTS: Of the 360 bacterial pathogens isolated from 348 patients, 57.8% were gram-positive and 42.2% were gram-negative. The common isolates were: Streptococcus species 76 (21.1%), coagulase-negative Staphylococci 75 (20.8%), Escherichia coli 43 (11.9%), Staphylococcus aureus 41 (11.4%). Overall, mortality was 21.3% (74/348). Staphylococcus species (Staphylococcus aureus and CoNS) were more commonly resistant to Trimethoprim/ Sulphamethoxazole (35.3%) and Penicillin (25.9%). Streptococcus species were resistant to Trimethoprim/Sulphamethoxazole (39.1%) and Erythromycin (19.6%). CONCLUSION: Bloodstream infections are important causes of morbidity and mortality in our patients, especially among chronically ill elderly adult males. Prescription of proven resistant antibiotics to suspected bacteremic patients needs attention in Dhahira region. PMID- 22043428 TI - An audit of hypertension at university health center in oman. AB - OBJECTIVES: To audit the documentation of medical care provided to hypertensive patients and to evaluate the management of hypertension in a primary healthcare center, Family Medicine Staff Clinic, Sultan Qaboos University (SQU) in Oman. METHODS: An audit of electronic medical records (EMR) was carried out during 2007and 2008 on a representative sample of 150 patients, selected randomly using a simple randomization method. The mean age of the patients was 54.8 +/- 9.9 years. The majority were Omanis; 53.3% were female, 46.7% were male. All patients' records were reviewed for proper recording in a pre designed structured form. Re-auditing was done in 2008. McNemar's test was used to compare data in 2007 with data in 2008. RESULTS: Age, gender, blood pressure recording, renal function tests, and lipid levels were sufficiently recorded (>75%) in the computer system. Histories of pertinent symptoms and smoking history were poorly recorded (<1%). Fifty-five percent of the hypertensive patients were sufficiently controlled (BP<140/90). There were significant differences between 2007 and 2008 with respect to documentation and recording of pertinent symptoms (p<0.001) and renal function tests (p=0.026). CONCLUSION: Conducting an audit of EMR is essential to evaluate clinical performance and to determine what changes should be made to improve quality of care. There was significant improvement in documentation of pertinent symptoms in the second audit. PMID- 22043429 TI - Effect of Mothers Nutritional Knowledge and Attitudes on Omani Children's Dietary Intake. AB - OBJECTIVES: The study investigates the dietary intakes of Omani preschoolers and associations with both socio-demographic characteristics and the mother's nutritional knowledge and attitudes. METHODS: A sample of 154 parents of preschoolers completed a questionnaire including socio-demographic characteristics, a food-frequency questionnaire to assess children's food intake, nutritional knowledge and attitudes towards healthy eating. RESULTS: The results showed a lower dietary adequacy of children's food intake in mothers with low educational levels, high-ranked occupation, and lower levels of both nutritional knowledge and food related health attitudes. The highest food intake and healthy eating attitude scores were found in children of mothers with high education level and mother without a job. The association of the dietary adequacy with socio-demographic background can help the Omani healthcare decision makers to develop better-tailored nutrition interventions which are more suitable for the Omani community. CONCLUSION: The results from this study of mothers' nutritional knowledge and attitudes support the inclusion of knowledge and attitudes in dietary interventions. PMID- 22043430 TI - Incidence of stomach cancer in oman and the other gulf cooperation council countries. AB - OBJECTIVES: Stomach cancer is the most common cancer among males in Oman and the second most frequent among females from 1997 to 2007. Reports have suggested the rate is higher in Oman than in the other GCC countries. This study aims to describe the epidemiology of stomach cancer in Oman and to explore the apparent differences in the incidence of stomach cancer between Oman and the other Gulf Cooperation Council (GCC) countries. METHODS: Data were obtained from the Omani National Cancer Registry (1997 - 2007) and from Gulf Centre for Cancer Registration reports (1998 - 2004). RESULTS: The annual average age-adjusted incidence rates for stomach cancer in Oman were 10.1 per 100,000 for males and 5.6 per 100,000 for females between 1997 and 2007. The age-adjusted incidence varied by region within Oman, and the incidence rate was higher in Oman than in most other GCC countries between 1998 and 2004. CONCLUSION: Further investigation of the completeness and accuracy of cancer registration is essential for exploration of variations in stomach cancer rates in the GCC countries. PMID- 22043431 TI - The association between body mass index, lipid profile and serum estradiol levels in a sample of iraqi diabetic premenopausal women. AB - OBJECTIVES: To evaluate the association between body mass index (BMI), serum lipid profile and estradiol level in a sample of Iraqi diabetic premenopausal women at their pre ovulatory period. METHODS: A total of 155 diabetic female patients aged between 20-45 years, were enrolled in this study, which was conducted in Al Khademiyia Teaching Hospital from July 2008 to January 2010. Venous blood samples were taken, each serum sample was analyzed for total cholesterol, triglycerides, high density lipoprotein - cholesterol (HDL-C), low density lipoprotein - cholesterol (LDL-C), fasting glucose, insulin and estradiol. Body weight and height were measured for all patients included to calculate their Body Mass Index. RESULTS: The age of diabetic patients was 29.7 +/- 4.3 years and BMI was 28.3 +/-5.84 kg/m(2). Fifty patients had normal BMI, while 50 patients were overweight and 55 were obese. The study revealed a positive association between obesity, triglycerides and LDL-C and a negative association between serum estradiol, obesity and LDL-C. CONCLUSION: Iraqi diabetic pre menopausal women at their pre ovulatory period exhibit a pro atherogenic risk profile because of their abnormal BMI, higher LDL-C, lower HDL cholesterol and estradiol level. PMID- 22043432 TI - Tuberculosis of the tongue clinically masquerading as a neoplasm: a case report and literature review. AB - Tuberculosis of the tongue is a very rare event even in areas and countries in which tuberculosis is endemic. The disease can present itself in a variety of clinical appearances, most of which may mimic malignant lingual neoplasms clinically. In this case, we present a patient who initially complained of an ulcerated lingual swelling, which was suspected to be a squamous cell carcinoma on clinical examination. In addition, the diagnosis was missed on the first and initial biopsy as it was not representative of the lesion. The diagnosis of lingual tuberculosis was made by histopathology on a second biopsy. In this article, we described the clinicopathological features of tuberculous glossitis with a comparison between our case and other similar reported cases in addition to a literature review. PMID- 22043433 TI - Native valve endocarditis caused by coagulase negative staphylococci; an appeal to start outpatient antimicrobial therapy: an unusual case report. AB - Coagulase negative staphylococci (CNS) were a rare cause of native valve endocarditis. However, they are emerging as an important cause of native valve endocarditis (NVE) in both community and healthcare settings. We describe a 64 yrs. old male who developed mitral valve endocarditis caused by coagulase negative staphylococci. There were no predisposing conditions or underlying cardiac disease that could have been the risk factor for the development of native valve infection. The patient had good recovery after six weeks of treatment with anti-staphylococcal antibiotics. PMID- 22043434 TI - Distal renal tubular acidosis, hypokalemic paralysis, nephrocalcinosis, primary hypothyroidism, growth retardation, osteomalacia and osteoporosis leading to pathological fracture: a case report. AB - Renal tubular acidosis (RTA) is a constellation of syndromes arising from different derangements of tubular acid transport. Recent advances in the biology of urinary acidification have allowed us to discern various molecular mechanisms responsible for these syndromes. RTA often presents as renal stone disease with nephrocalcinosis, ricket/osteomalacia and growth retardation in children with ultimate short stature in adulthood. The case reported here has features of distal renal tubular acidosis (dRTA), hypokalemic paralysis, primary hypothyroidism, growth retardation, osteomalacia and osteopenia leading to stress fracture. All these features presenting in a single case (as in our case) is a rare occurrence, so far other cases of distal renal tubular acidosis (dRTA) have been reported. PMID- 22043435 TI - Familial ectrodactyly syndrome in a nigerian child: a case report. AB - Ectrodactyly, also known as Split-Hand/Split-Foot Malformation (SHFM) is a rare genetic condition characterized by defects of the central elements of the autopod. It has a prevalence of 1:10,000-1:90,000 worldwide. The X-linked and autosomal dominant types have been described. It can occur as an isolated malformation or in combination with other anomalies, such as tibial aplasia, craniofacial defects, and genitourinary abnormalities. Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC) is an example of ectrodactyly syndrome accompanied by multiple organ defects. Ectrodactyly has been reported in Africa, especially in several families in remote areas of central Africa but there has not been any published work on ectrodactyly in Nigeria. A baby was born in Ilorin, North Central Zone of Nigeria, with an uneventful prenatal and delivery history but was noticed to have malformation of the two hands and the two lower limbs at birth which are replica of the father's malformation. We present this case to highlight familial ectrodactyly in Nigeria and prepare us to improve upon simple prenatal diagnosis and management of the challenges associated with patients with congenital malformation in Nigeria and other developing countries. PMID- 22043436 TI - Replantation of an amputated hand: a rare case report and acknowledgement of a multidisciplinary team input. AB - An amputation of the hand is a devastating injury. It adversely affects the victim's ability to earn a livelihood, support a family, and carry out daily activities. It has a great psychological impact. We report a middle aged male with an amputation at the level of the distal forearm who underwent replantation. The operative details of this case are described. Awareness of the possibility of salvage should be spread among healthcare personnel and the need for immediate attention by a multispeciality team is advocated. This report reviews the literature related to the operative technique, contraindications and long term results. PMID- 22043437 TI - An overlooked complication of vancomycin induced acute flaccid paralysis in a child with acute leukemia: a case report. AB - Vancomycin is a glycopeptide antibiotic which is commonly used to treat methicillin-resistant staphylococcal infections. It is commonly used in pediatric oncology wards for children with febrile neutropenia. We report a very rare side effect of vancomycin induced myopathy in a child with acute lymphoblastic leukemia. To the best of our knowledge, this is the first case reported from Oman. PMID- 22043438 TI - Spontaneous rupture of umbilical hernia in pregnancy: a case report. AB - A 28 year old woman presented with a spontaneous rupture of an umbilical hernia in her seventh month of pregnancy. She had four previous unsupervised normal deliveries. There was no history of trauma or application of herbal medicine on the hernia. The hernia sac ruptured at the inferior surface where it was attached to the ulcerated and damaged overlying skin. There was a gangrenous eviscerated small bowel. The patient was resuscitated and the gangrenous small bowel was resected and end to end anastomosis done. The hernia sac was excised and the 12 cm defect repaired. Six weeks later, she had spontaneous vaginal delivery of a live baby. We advocate that large umbilical hernias should be routinely repaired when seen in women of child bearing age. PMID- 22043439 TI - Cholera epidemic in and around kolkata, India: endemicity and management. PMID- 22043440 TI - Modification of the surgical morbidity and mortality meetings as a tool to improve patient safety. PMID- 22043441 TI - Laryngeal mass. PMID- 22043442 TI - Problem-based Learning: A Current Model of Education. PMID- 22043443 TI - Attitudes towards Informed Consent: A Comparison between Surgeons Working in Saudi Arabia and the United Kingdom. PMID- 22043444 TI - It's the Right Time for Advances in Nutrition. PMID- 22043445 TI - Editorial letter. PMID- 22043446 TI - (n-3) Fatty Acids: Clinical Trials in People with Type 2 Diabetes. AB - Recent human clinical trials of the effects of (n-3) fatty acids on participants with type 2 diabetes (T2D) were reviewed, focusing on 11 clinical trials conducted within the past 4 y, and subsequent to a Cochrane Database meta analysis of this topic. Doses of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in these studies were mostly in the range of ~2 g/d provided for 6 wk to 6 mo. Summarizing across these studies, there were no changes in fasting glucose or insulin compared with baseline or placebo. (n-3) Fatty acids generally decreased serum triglycerides but had varying effects on serum cholesterol, LDL cholesterol, and HDL cholesterol. A few studies indicated beneficial effects of (n-3) fatty acids on arterial blood flow. The effects of EPA and/or DHA have not yet been studied in clinical trials in participants at risk for T2D; the prevention or exacerbation of T2D by fish oil or EPA and DHA supplements of amounts >0.5 g/d deserves study. The prevention of adverse vascular effects of T2D by (n-3) fatty acids may be a promising direction for further study. PMID- 22043447 TI - Epigenetics: A New Bridge between Nutrition and Health. AB - Nutrients can reverse or change epigenetic phenomena such as DNA methylation and histone modifications, thereby modifying the expression of critical genes associated with physiologic and pathologic processes, including embryonic development, aging, and carcinogenesis. It appears that nutrients and bioactive food components can influence epigenetic phenomena either by directly inhibiting enzymes that catalyze DNA methylation or histone modifications, or by altering the availability of substrates necessary for those enzymatic reactions. In this regard, nutritional epigenetics has been viewed as an attractive tool to prevent pediatric developmental diseases and cancer as well as to delay aging-associated processes. In recent years, epigenetics has become an emerging issue in a broad range of diseases such as type 2 diabetes mellitus, obesity, inflammation, and neurocognitive disorders. Although the possibility of developing a treatment or discovering preventative measures of these diseases is exciting, current knowledge in nutritional epigenetics is limited, and further studies are needed to expand the available resources and better understand the use of nutrients or bioactive food components for maintaining our health and preventing diseases through modifiable epigenetic mechanisms. PMID- 22043448 TI - Pulse consumption, satiety, and weight management. AB - The prevalence of obesity has reached epidemic proportions, making finding effective solutions to reduce obesity a public health priority. One part of the solution could be for individuals to increase consumption of nonoilseed pulses (dry beans, peas, chickpeas, and lentils), because they have nutritional attributes thought to benefit weight control, including slowly digestible carbohydrates, high fiber and protein contents, and moderate energy density. Observational studies consistently show an inverse relationship between pulse consumption and BMI or risk for obesity, but many do not control for potentially confounding dietary and other lifestyle factors. Short-term (<=1 d) experimental studies using meals controlled for energy, but not those controlled for available carbohydrate, show that pulse consumption increases satiety over 2-4 h, suggesting that at least part of the effect of pulses on satiety is mediated by available carbohydrate amount or composition. Randomized controlled trials generally support a beneficial effect of pulses on weight loss when pulse consumption is coupled with energy restriction, but not without energy restriction. However, few randomized trials have been conducted and most were short term (3-8 wk for whole pulses and 4-12 wk for pulse extracts). Overall, there is some indication of a beneficial effect of pulses on short-term satiety and weight loss during intentional energy restriction, but more studies are needed in this area, particularly those that are longer term (>=1 y), investigate the optimal amount of pulses to consume for weight control, and include behavioral elements to help overcome barriers to pulse consumption. PMID- 22043449 TI - Functional amino acids in growth, reproduction, and health. AB - Amino acids (AA) were traditionally classified as nutritionally essential or nonessential for animals and humans based on nitrogen balance or growth. A key element of this classification is that all nonessential AA (NEAA) were assumed to be synthesized adequately in the body as substrates to meet the needs for protein synthesis. Unfortunately, regulatory roles for AA in nutrition and metabolism have long been ignored. Such conceptual limitations were not recognized until recent seminal findings that dietary glutamine is necessary for intestinal mucosal integrity and dietary arginine is required for maximum neonatal growth and embryonic survival. Some of the traditionally classified NEAA (e.g. glutamine, glutamate, and arginine) play important roles in regulating gene expression, cell signaling, antioxidative responses, and immunity. Additionally, glutamate, glutamine, and aspartate are major metabolic fuels for the small intestine and they, along with glycine, regulate neurological function. Among essential AA (EAA), much emphasis has been placed on leucine (which activates mammalian target of rapamycin to stimulate protein synthesis and inhibit proteolysis) and tryptophan (which modulates neurological and immunological functions through multiple metabolites, including serotonin and melatonin). A growing body of literature leads to a new concept of functional AA, which are defined as those AA that regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of organisms. Both NEAA and EAA should be considered in the classic "ideal protein" concept or formulation of balanced diets to maximize protein accretion and optimize health in animals and humans. PMID- 22043451 TI - Choline. PMID- 22043450 TI - Control of systemic iron homeostasis by the hemojuvelin-hepcidin axis. AB - Systemic iron homeostasis is maintained by the coordinate regulation of iron absorption in the duodenum, iron recycling of senescent erythrocytes in macrophages, and mobilization of storage iron in the liver. These processes are controlled by hepcidin, a key iron regulatory hormone. Hepcidin is a 25-amino acid peptide secreted predominantly from hepatocytes. It downregulates ferroportin, the only known iron exporter, and therefore inhibits iron efflux from duodenal enterocytes, macrophages, and hepatocytes into the circulation. Hepcidin expression is regulated positively by body iron load. Although the underlying mechanism of iron-regulated hepcidin expression has not been fully elucidated, several proteins have been identified that participate in this process. Among them, hemojuvelin (HJV) plays a particularly important role. HJV undergoes complicated post-translational processing in an iron-dependent manner, and it interacts with multiple proteins that are essential for iron homeostasis. In this review, I focus on the recent findings that elucidate the role of HJV and its interacting partners in the modulation of hepatic hepcidin expression. PMID- 22043452 TI - Institute of Medicine. 2010. Strategies to Reduce Sodium Intake in the United States. Washington, DC: The National Academies Press. PMID- 22043453 TI - C-Raf is required for the initiation of lung cancer by K-Ras(G12D). AB - The Ras/Raf/MEK/ERK (extracellular signal-regulated kinase) pathway is primarily responsible for mitogenesis in metazoans, and mutational activation of this pathway is common in cancer. A variety of selective chemical inhibitors directed against the mitogen-activated protein kinase pathway are now available for clinical investigation and thus the determination of the importance of each of the kinases in oncogenesis is paramount. We investigated the role of two Raf kinases, B-Raf and C-Raf, in Ras oncogenesis, and found that although B-Raf and C Raf have overlapping functions in primary mesenchymal cells, C-Raf but not B-Raf is required for the proliferative effects of K-Ras(G12D) in primary epithelial cells. Furthermore, in a lung cancer mouse model, C-Raf is essential for tumor initiation by oncogenic K-Ras(G12D), whereas B-Raf is dispensable for this process. Our findings reveal that K-Ras(G12D) elicits its oncogenic effects primarily through C-Raf and suggest that selective C-Raf inhibition could be explored as a therapeutic strategy for K-Ras-dependent cancers. PMID- 22043454 TI - The atomic force microscope as a mechano-electrochemical pen. AB - We demonstrate a method that allows the controlled writing of metallic patterns on the nanometer scale using the tip of an atomic force microscope (AFM) as a "mechano-electrochemical pen". In contrast to previous experiments, no voltage is applied between the AFM tip and the sample surface. Instead, a passivated sample surface is activated locally due to lateral forces between the AFM tip and the sample surface. In this way, the area of tip-sample interaction is narrowly limited by the mechanical contact between tip and sample, and well-defined metallic patterns can be written reproducibly. Nanoscale structures and lines of copper were deposited, and the line widths ranged between 5 nm and 80 nm, depending on the deposition parameters. A procedure for the sequential writing of metallic nanostructures is introduced, based on the understanding of the passivation process. The mechanism of this mechano-electrochemical writing technique is investigated, and the processes of site-selective surface depassivation, deposition, dissolution and repassivation of electrochemically deposited nanoscale metallic islands are studied in detail. PMID- 22043455 TI - Formation of SiC nanoparticles in an atmospheric microwave plasma. AB - We describe the formation of SiC nanopowder using an atmospheric argon microwave plasma with tetramethylsilane (TMS) as precursor. The impact of several process conditions on the particle size of the product is experimentally investigated. Particles with sizes ranging from 7 nm to about 20 nm according to BET and XRD measurements are produced. The dependency of the particle size on the process parameters is evaluated statistically and explained with growth-rate equations derived from the theory of Ostwald ripening. The results show that the particle size is mainly influenced by the concentration of the precursor material in the plasma. PMID- 22043456 TI - STM visualisation of counterions and the effect of charges on self-assembled monolayers of macrocycles. AB - Despite their importance in self-assembly processes, the influence of charged counterions on the geometry of self-assembled organic monolayers and their direct localisation within the monolayers has been given little attention. Recently, various examples of self-assembled monolayers composed of charged molecules on surfaces have been reported, but no effort has been made to prove the presence of counterions within the monolayer. Here we show that visualisation and exact localisation of counterions within self-assembled monolayers can be achieved with scanning tunnelling microscopy (STM). The presence of charges on the studied shape-persistent macrocycles is shown to have a profound effect on the self assembly process at the liquid-solid interface. Furthermore, preferential adsorption was observed for the uncharged analogue of the macrocycle on a surface. PMID- 22043457 TI - Highly efficient ZnO/Au Schottky barrier dye-sensitized solar cells: Role of gold nanoparticles on the charge-transfer process. AB - Zinc oxide (ZnO) nanorods decorated with gold (Au) nanoparticles have been synthesized and used to fabricate dye-sensitized solar cells (DSSC). The picosecond-resolved, time-correlated single-photon-count (TCSPC) spectroscopy technique was used to explore the charge-transfer mechanism in the ZnO/Au nanocomposite DSSC. Due to the formation of the Schottky barrier at the ZnO/Au interface and the higher optical absorptions of the ZnO/Au photoelectrodes arising from the surface plasmon absorption of the Au nanoparticles, enhanced power-conversion efficiency (PCE) of 6.49% for small-area (0.1 cm(2)) ZnO/Au nanocomposite DSSC was achieved compared to the 5.34% efficiency of the bare ZnO nanorod DSSC. The TCSPC studies revealed similar dynamics for the charge transfer from dye molecules to ZnO both in the presence and absence of Au nanoparticles. A slower fluorescence decay associated with the electron recombination process, observed in the presence of Au nanoparticles, confirmed the blocking of the electron transfer from ZnO back to the dye or electrolyte by the Schottky barrier formed at the ZnO/Au interface. For large area DSSC (1 cm(2)), ~130% enhancement in PCE (from 0.50% to 1.16%) was achieved after incorporation of the Au nanoparticles into the ZnO nanorods. PMID- 22043458 TI - Transport through molecular junctions. PMID- 22043459 TI - Interaction of spin and vibrations in transport through single-molecule magnets. AB - We study electron transport through a single-molecule magnet (SMM) and the interplay of its anisotropic spin with quantized vibrational distortions of the molecule. Based on numerical renormalization group calculations we show that, despite the longitudinal anisotropy barrier and small transverse anisotropy, vibrational fluctuations can induce quantum spin-tunneling (QST) and a QST-Kondo effect. The interplay of spin scattering, QST and molecular vibrations can strongly enhance the Kondo effect and induce an anomalous magnetic field dependence of vibrational Kondo side-bands. PMID- 22043460 TI - An MCBJ case study: The influence of pi-conjugation on the single-molecule conductance at a solid/liquid interface. AB - pi-Conjugation plays an important role in charge transport through single molecular junctions. We describe in this paper the construction of a mechanically controlled break-junction setup (MCBJ) equipped with a highly sensitive log I-V converter in order to measure ultralow conductances of molecular rods trapped between two gold leads. The current resolution of the setup reaches down to 10 fA. We report single-molecule conductance measurements of an anthracene-based linearly conjugated molecule (AC), of an anthraquinone-based cross-conjugated molecule (AQ), and of a dihydroanthracene-based molecule (AH) with a broken conjugation. The quantitative analysis of complementary current-distance and current-voltage measurements revealed details of the influence of pi-conjugation on the single-molecule conductance. PMID- 22043461 TI - Charge transport in a zinc-porphyrin single-molecule junction. AB - We have investigated charge transport in ZnTPPdT-Pyr (TPPdT: 5,15-di(p thiolphenyl)-10,20-di(p-tolyl)porphyrin) molecular junctions using the lithographic mechanically controllable break-junction (MCBJ) technique at room temperature and cryogenic temperature (6 K). We combined low-bias statistical measurements with spectroscopy of the molecular levels in the form of I(V) characteristics. This combination allows us to characterize the transport in a molecular junction in detail. This complex molecule can form different junction configurations, having an observable effect on the trace histograms and the current-voltage (I(V)) measurements. Both methods show that multiple, stable single-molecule junction configurations can be obtained by modulating the interelectrode distance. In addition we demonstrate that different ZnTPPdT-Pyr junction configurations can lead to completely different spectroscopic features with the same conductance values. We show that statistical low-bias conductance measurements should be interpreted with care, and that the combination with I(V) spectroscopy represents an essential tool for a more detailed characterization of the charge transport in a single molecule. PMID- 22043462 TI - Editorial: EJOI impact factor and EJOI-DENTSPLY Friadent Scientific Awards. PMID- 22043463 TI - Flapless versus open flap implant surgery in partially edentulous patients subjected to immediate loading: 1-year results from a split-mouth randomised controlled trial. AB - PURPOSE: To evaluate the efficacy of flapless versus open flap implant placement in partially edentulous patients. MATERIALS AND METHODS: Forty patients with two separate edentulous areas characterised by residual bone at least 5 mm thick and 10 mm in height had these sites randomised following a split-mouth design to receive at least one implant to each side after flap elevation or not. Implants were first placed in one site, and after 2 weeks in the other site freehand. Implants inserted with a torque >48 Ncm were immediately loaded with full occluding acrylic temporary restorations. Definitive single cemented crowns or screw-retained metal ceramic fixed dental prostheses were delivered after 2 months. Outcome measures were prosthesis and implant failures, complications, postoperative swelling and pain, consumption of analgesics, patient preference, surgical time, marginal bone level changes, and implant stability quotient (ISQ) values. RESULTS: Seventy-six implants were placed flapless and 67 after flap elevation. In the flapless group, four flaps had to be raised to control the direction of the bur, whereas one haemorrhage and one fracture of the buccal bone occurred in two patients of the flap elevation group. Four implants did not reach the planned stability (three belonging to the flapless group) and they were all immediately replaced by larger diameter ones. After 1 year, no drop-outs occurred. Two definitive bridges could not be placed when planned (one in each group) and two crowns had to be remade (one in each group). Two implants failed in each group, all in different patients. There were no statistically significant differences for prosthetic and implant failures, complications, ISQ values and marginal bone levels between groups. However, flapless implant placement required significantly less operation time (17 minutes less, saving almost two-thirds of the time for implant placement), induced less postoperative pain, swelling, analgesic consumption and was preferred by patients. Mean ISQ values of both groups significantly decreased over time. CONCLUSIONS: Implants can be successfully placed flapless and loaded immediately, reducing treatment time and patient discomfort. PMID- 22043464 TI - Treatment of the atrophic edentulous maxilla: short implants versus bone augmentation for placing longer implants. Five-month post-loading results of a pilot randomised controlled trial. AB - PURPOSE: To evaluate whether short (5 to 8.5 mm) dental implants could be a suitable alternative to longer (>11.5 mm) implants placed in atrophic maxillae augmented with autogenous bone for supporting dental prostheses. MATERIALS AND METHODS: Twenty-eight patients with fully edentulous atrophic maxillae having 5 to 9 mm of residual crestal bone height at least 5 mm thick, as measured on computerised tomography scans, were randomised into two groups either to receive 4 to 8 short (5 to 8.5 mm) implants (15 patients) or autogenous bone from the iliac crest to allow the placement of at least 11.5 mmlong implants (13 patients). Bone blocks and the windows at maxillary sinuses were covered with rigid resorbable barriers. Grafts were left to heal for 4 months before placing implants, which were submerged. After 4 months, provisional reinforced acrylic prostheses or bar-retained overdentures were delivered. Provisional prostheses were replaced, after 4 months, by definitive screw-retained metal-resin cross arch fixed dental prostheses. Outcome measures were: prosthesis and implant failures, any complications (including prolonged postoperative pain) and patient satisfaction. All patients were followed for 5 months after loading. RESULTS: All patients could be rehabilitated with implant-supported prostheses and none dropped out. One bilateral sinus lift procedure failed due to infection, though short implants could be placed. One implant failed in the augmented group versus 2 short implants in 2 patients. All failures occurred before loading. Significantly more complications occurred in augmented patients: 8 complications occurred in 5 augmented patients (all complained of pain 1 month after bone harvesting from the iliac crest). No complications occurred in the short implant group. All patients were fully satisfied with the treatment and would do it again. CONCLUSIONS: This pilot study suggests that short implants may be a suitable, cheaper and faster alternative to longer implants placed in bone augmented with autogenous bone for rehabilitating edentulous atrophic maxillae. However, these preliminary results need to be confirmed by larger trials with follow-ups of at least 5 years. PMID- 22043465 TI - Immediate loading of 2 (all-on-2) versus 4 (all-on-4) implants placed with a flapless technique supporting mandibular cross-arch fixed prostheses: preliminary results from a pilot randomised controlled trial. AB - PURPOSE: To evaluate the clinical outcome of 2 implants versus 4 implants placed flapless in fully edentulous mandibles and immediately restored with metal-resin screw-retained cross-arch prostheses. MATERIALS AND METHODS: Sixty patients from two different centres were randomised: 30 to the allon- 2 group and 30 to the all on-4 group. To be immediately loaded, implants had to be inserted with a minimum torque of 40 Ncm. Outcome measures were prosthesis and implant failures, and biological and biomechanical complications. RESULTS: Flaps were raised in 18 patients. Two implants in 2 patients did not reach the planned insertion torque and were immediately replaced by larger diameter ones. Four months after loading, no drop-out or implant failure occurred. One biomechanical complication occurred in the all-on-2 group versus 4 in the all-on-4 group. There were no statistically significant differences between groups for complications. There were no differences between centres. CONCLUSIONS: These very preliminary results, just 4 months after loading, suggest that immediately loaded mandibular cross-arch fixed dental prostheses can be supported by only 2 dental implants. Longer follow-ups (around 10 years) are needed to understand whether cross-arch mandibular prostheses can be successfully supported by only 2 dental implants. PMID- 22043466 TI - One versus two titanium screw fixation of autologous onlay bone grafts in the anterior maxilla: a randomised histological pilot study. AB - PURPOSE: The aim of this study was to compare the histological presentation of local mandibular bone grafts fixed with one screw or two screws in buccal anterior maxillary augmentation procedures. STUDY DESIGN: Local buccal defects of the anterior maxilla were reconstructed in 12 patients (mean age 47 +/- 17 years, range 18 to 67 years) using autogenous cortical bone grafts from the mandibular retromolar area. Patients were randomised using envelopes containing study identification numbers. After randomisation, two screws were used to fix the bone graft in six patients, and one screw was used in the other six patients. Four months later during implant placement, a bone biopsy was taken with a trephine. The biopsies were processed for light microscope evaluation. RESULTS: The mean total bone volume varied from 35.8% to 72.4% (mean 51.1% +/- 13.4%) in the one screw group and from 28.7% to 56.6% (mean 40.8% +/- 11.5%) in the two-screw group. The mean non-vital bone volume ranged from 0% to 2% (mean 0.9% +/- 0.9%) in the one-screw group and from 0% to 8.9% (mean 2.2% +/- 3.7%) in the two-screw group. The mean osteoid volume ranged from 2.2% to 7.3% (mean 5.4% +/- 1.7%) in the one-screw group and from 2.0% to 16.4% (mean 7.3% +/- 5%) in the two-screw group. CONCLUSION: No significant histological differences were found between the use of one or two screws to fix an autologous bone graft in buccal bone grafting procedures prior to implant placement. PMID- 22043467 TI - The rehabilitation of completely edentulous maxillae with different degrees of resorption with four or more immediately loaded implants: a 5-year retrospective study and a new classification. AB - PURPOSE: To report the long-term outcome of immediately loaded implants in the rehabilitations of completely edentulous maxillae with different classifications. The secondary aim was to evaluate the influence of possible explanatory variables on the incidence of biological and mechanical complications. MATERIAL AND METHODS: In total, 221 patients were consecutively included and classified into four groups that allowed implant placement in a vertical position: Group 1 (bone available up to first molar), Group 2 (bone available up to second premolar), Group 3 (bone available up to first premolar) and Group 4 (bone available up to canine). Outcome measures were prosthesis and implant survival, and biological and mechanical complications. RESULTS: A total of 995 implants were placed. Eighteen patients (8% of the sample) dropped out of the study. After 5 years, three patients lost their prosthesis due to implant failures, giving a survival rate of 98.6%; 25 patients lost 41 implants, giving a survival rate of 88.7% (25/221) and an implant-specific survival rate of 95.8% (41/995). According to the edentulism classification, the patient-specific survival rate after 5 years was 78.6% for Group 1, 89.3% for Group 2, 92.4% for Group 3 and 91.7% for Group 4. In total, 129 biological complications occurred affecting 129 implants (13%) in 66 patients (30%). Smoking was identified as a risk factor for the incidence of biological complications with an OR of 3.03 (95% CI 2.03-4.56; P < 0.0001), while 'gender' (male; OR = 0.56; 95% CI 0.37-0.85; P = 0.007) was a factor that had a protective effect. A total of 170 mechanical complications occurred, affecting 170 implants (17%) in 71 patients (38%). Bruxism was identified as a risk factor for the incidence of mechanical complications with an OR of 60.95 (95% CI 21.40-173.54; P < 0.0001), while a Group 2 edentulism classification had a protective effect for the incidence of mechanical complications with an OR of 0.22 (95% CI 0.07-0.71; P = 0.011). CONCLUSIONS: It is a viable treatment option to rehabilitate completely edentulous maxillae using four implants or more to support a fixed prosthesis. PMID- 22043468 TI - A retrospective cohort study of 105 patients rehabilitated with immediately loaded mandibular cross-arch bridges in combination with immediate implant placement. AB - PURPOSE: To evaluate the outcome of immediately loaded cross-arch bridges 4 months after loading. A second aim was to compare survival rates of implants placed in healed versus fresh extraction sites. MATERIALS AND METHODS: In total, 105 consecutive patients about to have their mandibles rendered fully edentulous (mean extractions per patient: 6.1 teeth) received four to six implants each (total number = 448), which were immediately placed in healed sites (266 implants, 59%) or fresh sockets (182 implants: 41%). Immediate loading of provisional prostheses was performed and all patients were followed-up for 4 months. The success criteria included prosthesis success, assessment of individual implant stability and complications. RESULTS: No patient dropped out and all 105 patients received definitive fixed prostheses after four months of loading. The overall implant survival rate after four months was 98.2%. Eight implants were lost in eight patients (8%). Four of them were inserted in fresh extraction sockets (2.2%) and four in healed sites (1.5%). No significant difference (P = 0.4990) was found for implants placed into healed sites versus fresh extraction sites. No complications were reported. CONCLUSIONS: Immediate implant placement and loading resulted in high implant as well as prosthetic survival rates. Placement in healed or fresh extraction bone sites did not influence implant survival. PMID- 22043469 TI - Outcome of implant therapy involving localised lateral alveolar ridge and/or sinus floor augmentation: a clinical and radiographic retrospective 1-year study. AB - AIM: To retrospectively evaluate the 1-year outcome of implant therapy involving various types of localised lateral alveolar ridge and/or sinus floor augmentation procedures performed before implant placement. MATERIALS AND METHODS: Forty-seven patients were consecutively treated with oral implants on average 6.5 months after bone grafting. A total of 82 regions were augmented and 151 implants were inserted. All regions were augmented with autogenous bone harvested intraorally. Block grafts (13 regions, 16%), particulate grafts (25 regions, 30%), and a combination of block and particulate grafts (44 regions, 54%) were used. The particulate grafts were sometimes mixed with less than 25% anorganic porous bovine-derived bone mineral (28 regions, 34%). Finally, the grafted areas were in most cases covered by either an expanded polytetrafluoroethylene (e-PTFE) membrane (58 regions, 71%) or a resorbable collagen membrane (11 regions, 13%). The selection of the performed procedure was based upon the experience of the surgeon and thorough evaluation of each case. All surgical procedures were performed by two oral and maxillofacial surgeons with extensive clinical experience with regenerative procedures. The outcome measures were complications related to the augmentation procedure, prosthesis survival, implant survival and peri-implant marginal bone loss. RESULTS: No dropouts occurred. Complications occurred in eight patients (17%) after bone harvesting: temporary paraesthesia (two patients, 4%), membrane exposure (five patients, 11%) and acute sinusitis (one patient, 2%). Membrane exposure was exclusively observed when an e-PTFE membrane was used. However, the subsequent implant placement was not compromised. Regarding the patient with acute sinusitis, the graft was removed and implant/prosthesis placement was not possible. No further prosthesis failures occurred during the 1-year follow-up period. Thus, the prosthesis survival was 99%. The implant survival involving sinus lift, lateral augmentation, and combined sinus lift and lateral augmentation was 91%, 97%, and 100%, respectively. A total of four patients (9%) experienced implant failure. The mean peri-implant marginal bone loss at patient level involving sinus lift, lateral augmentation, and combined sinus lift and lateral augmentation was 0.60 mm (range: 0.31-1.25), 0.31 mm (range: 0.00-0.75) and 0.41 mm (range: 0.00-1.25), respectively. No technical complications were observed. Moreover, no episodes of peri-implant mucositis or peri-implantitis were registered. CONCLUSIONS: Localised lateral alveolar ridge and/or sinus floor augmentation performed before implant placement seems to be associated with few complications after 1 year. However, it should be emphasised that all surgical procedures were selected and performed by oral and maxillofacial surgeons with extensive clinical experience in the field of regenerative procedures. PMID- 22043470 TI - A proposed classification for zygomatic implant patient based on the zygoma anatomy guided approach (ZAGA): a cross-sectional survey. AB - PURPOSE: The aim of the present cross-sectional study was to propose a classification system based on a cross-sectional survey of zygomatic implant cases. MATERIALS AND METHODS: Cone beam computerised tomography (CBCT) postoperative images and clinical intra-surgery photographs of 200 sites corresponding to 100 patients, treated with a total of 198 zygomatic implants in the maxilla according to an anatomy-driven prosthetic approach, were reviewed with regard to anatomy and pathway of the zygomatic implant body. The patients were consecutively selected independently of the type of surgery performed, with the unique requirement of a post-surgical CBCT performed at the moment of selection. Of special interest was the morphology of the lateral sinus wall, residual alveolar crest and the zygomatic buttress. An attempt was made to divide the patients into groups, describing typical anatomies and implant pathways. RESULTS: Five basic skeletal forms of the zygomatic buttress-alveolar crest complex and subsequent implant pathways could be identified in a sample of 100 patients. Out of them, 62% were female and 38% male, with ages varying between 36 and 83 years (mean age 59.6, SD: 9.67). The five groups were classified as ZAGA 0 to 4 representing 15%, 49%, 20.5%, 9% and 6.5% of the studied sites, respectively. Intra-individual anatomical differences affecting the zygomatic buttress-alveolar crest complex was also found in 58% of the patients. CONCLUSIONS: Five typical anatomical and implant pathway situations could be identified. A classification system comprising five groups named ZAGA 0 to 4 is proposed. Anatomical intra-individual differences were also found in the 58% of the studied population. It is believed that the proposed classification system is useful for categorising zygomatic implant cases for therapy planning and for scientific follow-up purposes. PMID- 22043471 TI - Influence of operator experience on in vitro bond strength of dentin adhesives. AB - PURPOSE: To examine the influence of operator experience level on shear bond strength (SBS) of a self-etching adhesive (Clearfil SE Bond [CSE], Kuraray) and an etch-and-rinse adhesive (Single Bond [SB], 3M ESPE). MATERIALS AND METHODS: Flat dentin surfaces were created on 120 extracted human third molars. Bonding agents and composite resin were applied and light cured according to manufacturers' directions (n = 15). Four operators with different levels of experience in operative dentistry performed the same specimen preparation steps independently: group 1: specialist in operative dentistry; group 2: post-graduate student; group 3: undergraduate dental student; group 4: private general practitioner. Specimens were stored in distilled water for 24 h at 37 degrees C before SBS testing. Statistical analyses were carried out with Mann-Whitney U- and Kruskall-Wallis tests. RESULTS: For CSE, mean SBS and standard deviations were: (1) 54.4 +/- 15.6(a), (2) 55.3 +/- 7.6(a), (3) 49.4 +/- 10.5(ab), (4) 41.6 +/- 13.1(b). For SB, they were: (1) 28.6 +/- 10.3(c), (2) 32.7 +/- 11.2(c), (3) 17.5 +/- 5.6(d), (4) 24.4 +/- 9.5(cd). Groups with the same superscript letters are not significantly different. CSE showed higher bond strengths than SB in all groups (p < 0.05). There was no significant difference in mean bond strengths between groups 1 and 2 for each adhesive (p > 0.05). Depending on the adhesives, groups 3 and 4 were significantly different from groups 1 and 2, but not different from each other. CONCLUSION: Operator experience influences dentin bond strength values of dentin adhesives. An increased level of experience with a specific adhesive system and the associated application procedures correlates with higher SBSs. PMID- 22043472 TI - The effects of aging on shear bond strength and nanoleakage expression of an etch and-rinse adhesive on human enamel and dentin. AB - PURPOSE: To evaluate the effects of increasing thermocycling regimens on bond strength and nanoleakage of an etch-and-rinse adhesive. MATERIALS AND METHODS: Adper Single Bond (3M ESPE) was used for bonding resin composite to human enamel and dentin. Specimens were stored in water (37 degrees C, 24 h) and subjected to thermocycling (5 degrees C and 55 degrees C) in five groups: 1. control (no thermal cycling), 2. 100, 3. 500, 4. 2000, or 5. 10,000 cycles. The microshear bond test was performed at a crosshead speed of 1 mm/min (n = 16). Nanoleakage specimens were immersed in silver nitrate and FE-SEM micrographs were digitally analyzed to calculate silver penetration in three samples. RESULTS: The mean bond strength to enamel was not significantly affected by thermocycling. However, artificial aging decreased dentin bond strength in groups 4 and 5 compared to control. Weibull analysis indicated that the characteristic strength decreased gradually with aging in both substrates. All groups exhibited some nanoleakage, and a significant increase in silver penetration compared to the control was observed in enamel and dentin groups 2 to 5. CONCLUSION: A nanoleakage increase was detected in an earlier stage of aging than when a significant drop in bond strength was observed, with the dentin bond being more susceptible to deterioration. PMID- 22043473 TI - Evaluation of a new universal primer for ceramics and alloys. AB - PURPOSE: To evaluate in vitro the effect of using a universal primer on the resin bond strength to ceramics (silicate and zirconia) and two noble alloys for metal ceramic restorations. MATERIALS AND METHODS: Disk-like specimens made of four dental restoration materials (silicate ceramic, zirconia ceramic, gold-based alloy and palladium-based alloy) were ground with abrasive paper, prepared for bonding (silicate ceramic: etching with 5% hydrofluoric acid for 60 s; the other materials: air abrasion with 50-um Al2O3 at 2.5 bar) and ultrasonically cleaned in 96% isopropanol. Eight specimens of each material were primed with a universal primer, 8 specimens were primed with a well-established material-specific method (silicate ceramic: silanization; zirconia ceramic: phosphate monomer-containing primer; alloys: sulfuric monomer-containing primer). Plexiglas tubes filled with a composite resin were bonded to the specimens using an alignment apparatus and a composite luting resin. After storage in 37 degrees C tap water for three days, or 167 days with additional thermocycling, tensile bond strength (TBS) was measured in a universal testing machine at a crosshead speed of 2 mm/min. RESULTS: After 167 days of storage, median TBS values for each material were (well-established method/universal primer) 40 MPa/37 MPa (silicate ceramic), 41 MPa/41 MPa (zirconia ceramic), 20 MPa/17 MPa (gold-based alloy), and 20 MPa/19 MPa (palladium-based alloy). Statistical analysis revealed no statistically significant differences among control groups and test groups. CONCLUSION: The universal primer seems to be a promising alternative compared to using three different primers for alloys, silicate and zirconia ceramics. PMID- 22043474 TI - Ethics of a clinical trial. PMID- 22043475 TI - Patellofemoral knee pain treatment using neuromuscular retraining of the hip musculature in an adolescent female: a case report. AB - The purpose of this case study is to demonstrate the treatment of patella-femoral knee pain in an adolescent female athlete with emphasis on neuromuscular training of the knee and hip in synergy movement strategies. A 1.67-m, 61.5-kg, 15-year old woman athlete reported to rehabilitation with the complaint of a 1-year history of bilateral knee pain. The patient noted that the symptoms were exacerbated with any sports-specific training. The patient played softball as an infielder. The athlete was referred by her family practice physician. After the patient was assessed, a clinical hypothesis was generated. It was thought that neuromuscular dysfunction of the hips and knees was causing faulty knee mechanics. These abnormal mechanics were presenting as patella-femoral knee pain. Initially, the athlete was assigned a home exercise program of side-lying hip abduction and lateral step-downs. At her first follow-up appointment, she noted increased symptoms that were aggravated with her home program. Upon inspecting her exercise technique, faulty step-down mechanics were contributing to her symptoms. Step-downs were discontinued, and the patient was instructed in and performed a chair squatting exercise, which was added to her home program. At her next follow-up, the patient noted being asymptomatic for 2 days. Her exercises were increased in intensity to include a Stairmaster and hip abduction and adduction on a 4-way hip machine. Eventually, over her treatment course, perturbation and proprioceptive training were initiated. By the sixth visit, the patient reported no symptoms and felt comfortable with self-management. A phone interview 3 months later indicated that the patient had no recurrent symptoms and was participating in sports without difficulty. This case demonstrates effectiveness of using hip and knee joint synergy to treat patella-femoral pain (PFP). The use of this synergy promotes proper patella-femoral alignment and improved knee mechanics. This case also is unique in the lack of physical agents and taping used to improve the patient's condition. It reinforces how exercise technique can carry over to functional athletic activities. This study provides a case for the use of hip and knee mechanical retraining in the treatment of PFP in adolescent female athletes who do not exhibit abnormal foot mechanics in weight bearing. It is important that sports medicine professionals be aware of these treatment options and are able to use them to correct these deficits in order to facilitate return to training and competition as quickly and safely as possible. PMID- 22043476 TI - [Medicinal plants against malaria?]. PMID- 22043477 TI - [Vulgar cochranism in practice]. PMID- 22043478 TI - The male phenotype in osteopathia striata congenita with cranial sclerosis. AB - Osteopathia striata with cranial sclerosis (OSCS) is an X-linked disease caused by truncating mutations in WTX. Females exhibit sclerotic striations on the long bones, cranial sclerosis, and craniofacial dysmorphism. Males with OSCS have significant skeletal sclerosis, do not have striations but do display a more severe phenotype commonly associated with gross structural malformations, patterning defects, and significant pre- and postnatal lethality. The recent description of mutations in WTX underlying OSCS has led to the identification of a milder, survivable phenotype in males. Individuals with this presentation can have, in addition to skeletal sclerosis, Hirschsprung disease, joint contractures, cardiomyopathy, and neuromuscular anomalies. A diagnosis of OSCS should be considered in males with macrocephaly, skeletal sclerosis that is most marked in the cranium and the absence of metaphyseal striations. The observation of striations in males may be indicative of a WTX mutation in a mosaic state supporting the contention that this sign in females is indicative of the differential lyonization of cells in the osteoblastic lineage. PMID- 22043479 TI - Feedback: a perennial problem. PMID- 22043480 TI - Relationship between anthropometric and physiological characteristics in youth soccer players. PMID- 22043481 TI - Team Based-Learning (TBL) as a primary strategy for the development of generic competences in medical students: the Peruvian case. PMID- 22043482 TI - The road to residency and beyond for international medical graduates in the United States. PMID- 22043483 TI - Beware the commodification of medical education? PMID- 22043484 TI - Somatic mutations in NKX2-5, GATA4, and HAND1 are not a common cause of tetralogy of Fallot or hypoplastic left heart. AB - The majority of congenital heart disease (CHD) occurs as a sporadic finding, with a minority of cases associated with a known genetic abnormality. Combinations of genetic and environmental factors are implicated, with the recent and intriguing hypothesis that an apparently high rate of somatic mutations might explain some sporadic CHD. We used samples of right ventricular myocardium from patients undergoing surgical repair of tetralogy of Fallot (TOF) and hypoplastic left heart (HLH) to examine the incidence of somatic mutation in cardiac tissue. TOF is a common form of cyanotic CHD, occurring in 3.3 per 10,000 live births. HLH is a rare defect in which the left side of the heart is severely under-developed. Both are severe malformations whose genetic etiology is largely unknown. We carried out direct sequence analysis of the NKX2-5 and GATA4 genes from fresh frozen cardiac tissues and matched blood samples of nine TOF patients. Analysis of NKX2-5, GATA4, and HAND1 was performed from cardiac tissue of 24 HLH patients and three matched blood samples. No somatic or germline mutations were identified in the TOF or HLH patients. Although limited by sample size, our study suggests that somatic mutations in NKX2-5 and GATA4 are not a common cause of isolated TOF or HLH. PMID- 22043485 TI - Student-led outreach: exploring academic medicine at a pre-university level. PMID- 22043486 TI - Does a multi component palliative care education programme help medical students talk with patients at end-of-life? PMID- 22043487 TI - Analysis of genomewide association signals for nonsyndromic cleft lip/palate in a Kenya African Cohort. AB - Nonsyndromic cleft lip with or without cleft palate is a common birth defect with a wide range of prevalence among different populations, apparently highest in Asians and Amerindians and lowest in Africans. Recent genomewide association studies of European-derived and Asian populations have identified six confirmed loci for this phenotype: 1p22.1, 1q32.2 (IRF6), 8q24, 10q25.3, 17q22, and 20q12. However, there have thus far been no studies of these loci in African patients with nonsyndromic cleft lip with or without cleft palate. We carried out association analysis of SNPs in these six candidate chromosomal regions in 128 nonsyndromic cleft lip with or without cleft palate cases and 105 controls from the Rift Valley of Kenya. We observed no apparent association of this phenotype with any of these SNPs, though there was strong statistical power only for 8q24. These results indicate that at least the 8q24 locus does not play a major role in the pathogenesis of nonsyndromic cleft lip with or without cleft palate in east Africa, supporting locus heterogeneity for susceptibility to this phenotype among different major populations of the world. PMID- 22043488 TI - MODY type 2 in Greig cephalopolysyndactyly syndrome (GCPS) as part of a contiguous gene deletion syndrome. AB - Maturity-onset diabetes of the young type 2 (MODY2) is a form of monogenic diabetes, characterized by mild fasting hyperglycemia. MODY2 is caused by heterozygous mutations in the GCK gene that encodes the glucokinase enzyme. We describe the clinical features and the underlying genetic defect of MODY2 in a patient with atypical Greig cephalopolysyndactyly syndrome (GCPS). The patient presented with the limb formation and the craniofacial developmental abnormalities typical to GCPS, in addition to mental retardation and epilepsy (assigned as atypical syndrome). Fasting hyperglycemia in the diabetic range, impaired glucose tolerance, and lack of diabetes autoantibodies were compatible with MODY2. In order to delineate the genetic aberrations relevant both to MODY2 and Greig syndrome in this patient, we performed cytogenetic analysis, real-time PCR of the GCK gene, and comparative genomic hybridization (CGH) array. Cytogenetic study has shown a microscopic detectable deletion in the 7p13-15 chromosomal region. Real-time PCR demonstrated a deletion of the GCK gene in the patient but not her parents, and CGH array revealed a deleted region of approximately 12 Mb in the 7p13-15 region. This deleted region included GLI3 and GCK genes (where heterozygous mutations cause GCPS and MODY2, respectively), and many other contiguous genes. Our patient manifests a unique form of MODY2, where GCK gene deletion is part of a large deleted segment in the 7p13-15 chromosomal region. PMID- 22043489 TI - A de novo 2.1-Mb deletion of 13q12.11 in a child with developmental delay and minor dysmorphic features. AB - We report on a patient with an interstitial deletion at 13q12.11. He had mild developmental delay, craniofacial dysmorphism, a pectus excavatum, narrow shoulders, malformed toes, and cafe-au-lait spots. Array CGH analysis disclosed a de novo deletion spanning 2.1 Mb,within cytogenetic band 13q12.11.The deletion produces hemizygozity for 16 known genes, among which GJA3, GJB2, GJB6, IFT88, LATS2, and FGF9 have potential clinical significance. The observed phenotype may be due to mutation in one of the 16 genes, or to a combination of deletion and/or mutation in a number of them. PMID- 22043490 TI - China's fertility policy persists, despite debate. PMID- 22043491 TI - Nothing but flowers. PMID- 22043492 TI - Doing away with 12-hour shifts. PMID- 22043493 TI - Oncoplastic multidisciplinary meetings: a necessity or luxury? AB - Although there is scant evidence to support multidisciplinary meetings in any cancer specialty, they are now regarded as best practice. We believe the oncoplastic multidisciplinary meeting plays a similarly important role, consolidating oncoplastic multidisciplinary working and allowing transparent decision making, standardisation of care and recording of results. This may drive oncoplastic surgery to an evidence-based position from which oncoplastic excellence can be achieved. PMID- 22043494 TI - [From the lack of transferability of international guidelines for thyroid diagnosis]. PMID- 22043496 TI - Two-finger homodigital web advancement flap. AB - Fingertip amputation is a common hand injury and various techniques for reconstruction have been described. Important considerations to take into account when planning reconstruction are maintaining length and preserving function. This paper describes a technique for reconstructing the amputated fingertips of two adjacent digits. PMID- 22043497 TI - Embolisation of Angio-SealTM device: an unusual case of post-cardiac catheterisation limb ischaemia. AB - We present the case of a 67-year-old male presenting with critical limb ischaemia following cardiac catheterisation. Immediately after deployment of an arterial closure device, the patient reported severe lower limb pain with impalpable pulses. Magnetic resonance angiography revealed an abrupt disruption of flow in the tibioperoneal trunk. Subsequent surgery revealed embolisation of the arterial closure device. The patient went on to make an unremarkable recovery. PMID- 22043498 TI - Click to join peptides/proteins together. AB - Copper(I) is able to catalyze Huisgen 1,3-dipolar cycloaddition in a "click" fashion. This copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction presents excellent chemoselectivity and occurs over a wide-range of reaction conditions. It shows tolerance to variation in both pH and solvent polarity, thereby facilitating the ligation of peptides and proteins to produce peptidomimetics and synthetic proteins. In addition, the only product formed is a 1,4-disubstituted-1,2,3-triazole moiety, in many aspects resembling the natural peptide bond, including hydrogen-bonding capability, planarity, distance between the 1 and 4 substituents, and conformational restriction of the peptide backbone; thus the triazole-backbone-modified peptide, in which a triazole replaces the amide bond, may be anticipated to present a secondary structure similar to that of its natural counterpart. This Focus Review describes the scope and applications of copper(I)-catalyzed alkyne-azide cycloaddition in synthetic peptide/protein chemistry. PMID- 22043499 TI - A highly selective and sensitive polymer-based fluorescence sensor for Hg2+-ion detection via click reaction. PMID- 22043500 TI - Unraveling gold(I)-specific action towards peptidic disulfide cleavage: a DFT investigation. AB - Ground-state disulfide dissociation is a target of prime importance in structural biochemistry. A main difficulty consists in avoiding competition with carbon sulfur and backbone scission pathways. In tandem mass spectrometry, such selectivity is afforded using transition elements or coinage-metal ions as catalyst. Yet, the underlying gas-phase mechanistic details remain poorly understood. Gold(I)-assisted disulfide cleavage is investigated by means of DFT calculations, to elucidate the highly selective and specific catalytic action of this transition-metal cation, a most promising one in tandem mass spectrometry. The preferential cleavage of sulfur-sulfur versus carbon-sulfur linkages on dimethyldisulfide, taken as a prototypical aliphatic compound, is rationalized on the basis of molecular orbital arguments. Secondly, it is revealed that the disulfide dissociation profile is dramatically impacted by a peptidic environment. Calculations on L,L-cystine derivatives show two main factors: the topological frustration for an embedded -CH(2)-S-S-CH(2)- motif induces a 5 kcal mol(-1) penalty, whereas electrophilic assistance via complexation of nitrogen and oxygen atoms lowers activation barriers by a factor of 3. S-S weakening is both thermodynamically and kinetically driven by the versatile coordination mode of gold(I). The influence of amine-terminus group protonation is finally sketched: it gives rise to an intermediate reactivity. This study sheds lights on the key action of the peptidic environment in tuning the dissociation profile in the presence of this transition-metal monocation. PMID- 22043501 TI - Prognostic significance of p53 and KAI-1 expression in patients with laryngeal squamous cell carcinoma. AB - OBJECTIVE: To examine the prognostic significance of the immunohistochemical expression of p53 and KAI-1 oncoproteins in patients with laryngeal squamous cell carcinoma. STUDY DESIGN: A retrospective evaluation was developed on 82 patients with primary laryngeal squamous cell carcinoma treated by primary surgery. For the immunohistochemical evaluation, formalin-fixed and paraffin-embedded tissue blocks from resection were used. Clinicopathologic data were correlated with the staining results. RESULTS: The results of the immunohistochemical examination showed a statistically significant relationship between down-regulation of KAI-1 protein expression, increase of the histologic grading, and primary tumors associated with lymph node metastases. On the other hand, no statistical correlation was evidenced between p53 up-regulation and clinicopathologic data or between the two markers. CONCLUSION: Our results suggest that KAI-1 may become an important biomarker that could help in selection of high-risk patients with laryngeal squamous cell carcinoma who may benefit from more aggressive therapy or chemoprevention. PMID- 22043502 TI - Usefulness and limitations of alpha-methylacyl-CoA racemase expression in the hepatobiliary system and pancreas: a wide tissue microarray analysis of normal and neoplastic epithelia. AB - OBJECTIVE: To establish the frequency, significance and clinical utility of alpha methylacyl-CoA racemase (AMACR) expression in the hepatobiliary system by performing a wide immunohistochemical screening of AMACR expression. STUDY DESIGN: A total of 204 neoplastic, preneoplastic and normal samples from the hepatobiliary and pancreatic system were immunohistochemically studied on tissue microarrays for AMACR expression and correlated with clinicopathologic parameters. RESULTS: Hepatocellular carcinomas (HCC) showed intense AMACR expression, which was significantly stronger than in nonmalignant tissues and correlated with good differentiation but not with evolution. Weak AMACR expression was observed in cholangiocarcinomas and preneoplastic pancreatic lesions. HCC showed stronger expression than cholangiocarcinomas and ductal pancreatic adenocarcinomas. DISCUSSION: AMACR is strongly expressed in some neoplastic and preneoplastic lesions of the hepatobiIiary system, mainly HCC, and may play a role in malignant transformation and be useful in the differential diagnosis. PMID- 22043503 TI - Effects of image resolution and noise on estimating the fractal dimension of tissue specimens. AB - OBJECTIVE: To investigate the effects of imaging system noise and resolution on the ability to estimate and distinguish relative differences in the fractal dimension of tissue specimens. STUDY DESIGN: Mathematically derived test images of known fractal dimension mimicking the complexity of epithelial morphology were created. The box-counting method was used to compute fractal dimension. To study the effects of resolution on fractal dimension, the test images were convolved with Gaussian point spread functions (PSF), and effects of noise were studied by adding Poisson and Gaussian noise. Application of these findings was illustrated by measuring the resolution and noise for a typical optical microscope and digital camera (OMDC) system. RESULTS: Poor spatial resolution reduces the fractal dimension and has an increased adverse effect on higher dimensions. Fractal dimension can be estimated within 7% of the true dimension, and relative differences of 0.1 between dimensions are distinguishable provided the PSF of an imaging system has a full-width-at-half-maximum < or = 4 pixels and the contrast to-noise ratio > 15. These conditions were satisfied by our OMDC. CONCLUSION: Effects of noise and resolution from a typical OMDC system do not significantly inhibit the ability to estimate and distinguish relative differences in the fractal dimension of tissue specimens. PMID- 22043504 TI - Quantificational and statistical analysis of the differences in centrosomal features of untreated lung cancer cells and normal cells. AB - OBJECTIVE: To distinguish untreated lung cancer cells from normal cells through quantitative analysis and statistical inference of centrosomal features extracted from cell images. STUDY DESIGN: Recent research indicates that human cancer cell development is accompanied by centrosomal abnormalities. For quantitative analysis of centrosome abnormalities, high-resolution images of normal and untreated cancer lung cells were acquired. After the images were preprocessed and segmented, 11 features were extracted. Correlations among the features were calculated to remove redundant features. Ten nonredundant features were selected for further analysis. The mean values of 10 centrosome features were compared between cancer and normal cells by the two-sample t-test; distributions of the 10 features of cancer and normal centrosomes were compared by the two-sample Kolmogorov-Smirnov test. RESULTS: Both tests reject the null hypothesis; the means and distributions of features coincide for normal and cancer cells. The 10 centrosome features separate normal from cancer cells at the 5% significance level and show strong evidence that all 10 features exhibit major differences between normal and cancer cells. CONCLUSION: Centrosomes from untreated cancer and normal bronchial epithelial cells can be distinguished through objective measurement and quantitative analysis, suggesting a new approach for lung cancer detection, early diagnosis and prognosis. PMID- 22043505 TI - Mean nuclear volume in complex atypical hyperplasia and adenocarcinoma of the endometrium. AB - OBJECTIVE: To explore the possible role of mean nuclear volume (MNV) in differentiating complex atypical hyperplasia (CAH) from well-differentiated adenocarcinoma (WDAC) of the endometrium. STUDY DESIGN: In this retrospective study we measured MNV in 15 cases each of CAH and WDAC using the point intercepts method. At least 100 nuclei were selected for MNV estimation in each case. RESULTS: The mean MNV in CAH was 430.06 microm3 (SD 232.43); the MNV in WDAC was 753.14 microm3 (SD 322.87). Independent sample t test showed significant difference (p < 0.005) of MNV between CAH and WDAC. CONCLUSION: MNV determination resulted in a wide-ranging overlap of distributions for CAH and WDAC cases, such that at best only a modest proportion of cases with very low MNV values offer a diagnostic clue. PMID- 22043506 TI - Mature cystic teratoma of the appendix: a case report. AB - BACKGROUND: Teratomas very rarely arise from the appendix. To our knowledge, only one prior case of mature teratoma involving the appendix has been reported in the medical literature. CASE: Our case is the second reported case of mature cystic teratoma involving the appendix, and, to our knowledge, it is the first reported in a female who had two simultaneous teratomas, one arising from the appendix and one arising from the right ovary. CONCLUSION: Although mature cystic teratoma is a rare tumor of the appendix, it should be considered in the differential diagnosis of appendiceal masses. The differential diagnosis of appendiceal masses, including clinical and pathologic features, is discussed in detail. PMID- 22043507 TI - Coexistence of bladder prostatic-type polyp and urothelial papilloma. PMID- 22043508 TI - Mental health of workers. PMID- 22043509 TI - The drugs don't work? PMID- 22043510 TI - Read all about it. PMID- 22043511 TI - What stops those with mental health conditions from returning to work? PMID- 22043512 TI - Welfare writes. 'Migration' from incapacity benefit to employment and support allowance (ESA). PMID- 22043513 TI - Outside the box. Physical and verbal abuse of people with learning disabilities. PMID- 22043514 TI - The bigger picture. Mental health treatment is an expensive area of health and social care. PMID- 22043515 TI - A child in mind. PMID- 22043516 TI - Antipsychotic medicine and mental health. PMID- 22043517 TI - Doctor's orders. PMID- 22043518 TI - For persons with mental disorders, joining a photography club can be a great way to meet people. PMID- 22043519 TI - The impact of adult and community learning programmes on mental health and wellbeing. PMID- 22043520 TI - Living in the here and now. PMID- 22043521 TI - On the record. Looking at ordinary people's tales of living with their mental illness. Interview by Alita Howe. PMID- 22043522 TI - [ASLE for chemicals in the air of workplace. History, contemporary state, prospects]. AB - The authors followed historical background of occurrence, development, transformation and contemporary state of topic concerning ASLE for chemicals in the air of workplace over 1977-2010 in USSR and Russian Federation. The article covers prospects to improve regulation and methodic aspects of prompt regulation for industrial chemicals in the air of workplace. PMID- 22043523 TI - [Regulations for decontamination of surfaces polluted as a result of chemical accidents (concept approaches)]. AB - The threat of industrial chemical accidents and terrorist attacks requires the development of safety regulations for the cleanup of contaminated surfaces. This paper presents principles and a methodology for the development of a new toxicological parameter, "relative value unit" (RVU) as the primary decontamination standard. PMID- 22043524 TI - [Under the knife for beauty. Also (elderly) men are becoming increasingly more vain]. PMID- 22043525 TI - A moving target, the usual suspects and (maybe) a smoking gun: the problem of pinning blame in modern genocide. PMID- 22043526 TI - British development policies and malaria in India: 1897-c.1929. PMID- 22043527 TI - Findings of research misconduct. PMID- 22043528 TI - Common land, poor relief and enclosure: the use of manorial resources in fulfilling parish obligations, 1601-1834. PMID- 22043529 TI - "Danger is looming here." Moral panic and urban children's and youth culture in Denmark, 1890-1914. PMID- 22043530 TI - Dangerous media? Panic discourses and dilemmas of modernity. PMID- 22043531 TI - Faithful servants and dangerous beasts: race, nationalism and historical mythmaking. PMID- 22043532 TI - Freudians and feminists in Fin-de-siecle Vienna. PMID- 22043533 TI - [We know Frobenius more or less: on the inconclusive in ethnology]. PMID- 22043534 TI - Abstracts of the COSA (Clinical Oncological Society of Australia) 38th Annual Scientific Meeting. November 15-17, 2011. Perth, Western Australia, Australia. PMID- 22043535 TI - The zebrafish. Preface. PMID- 22043536 TI - Gambling and Venetian noblemen c.1500-1700. PMID- 22043537 TI - [Leo Frobenius, or the enthusiasm for German ethnology]. PMID- 22043538 TI - Marriage transactions in renaissance Italy and Mauss's essay on the Gift. PMID- 22043539 TI - "Measures are being taken to eliminate the consequences of the accident": ideology and the Soviet response to the Chornobyl accident. PMID- 22043540 TI - Methodist education and the social status of the Straits Chinese in colonial Singapore (1886-1914). PMID- 22043541 TI - Reconstituting the social after the Terror: family, property and the law in popular politics. PMID- 22043542 TI - Schools of revolt: syndicalist education and workers' culture in pre-World War I France. PMID- 22043543 TI - Selling racism: history, heritage, gender and the (re)production of prejudice. PMID- 22043544 TI - Unruptured intracranial aneurysms: some questions answered, many questions remain. Re: Pelz D. CURES and the dilemma of unruptured intracranial aneurysms. Can J Neuro Sci. 2011 Mar;38(2):191-2. PMID- 22043545 TI - Ethanol abuse after a right temporal lobe resection for intractable epilepsy. PMID- 22043546 TI - A case of bilateral homonymous hemianopsia with macular sparing. PMID- 22043547 TI - Paraneoplastic encephalomyelitis, stiff person syndrome and breast carcinoma. PMID- 22043548 TI - A case of phenytoin-induced encephalopathy in a mathematician with Stage IV NSCLC. PMID- 22043549 TI - Spinal cord injury after prolonged neck flexion, is it an underestimated risk? PMID- 22043550 TI - Isolated unilateral hypoglossal nerve palsy. PMID- 22043551 TI - Melanoma-associated retinopathy report of a case and review. PMID- 22043552 TI - Optimal positioning of occupational therapy. AB - BACKGROUND: Occupation is central to occupational therapy. Although occupation is a universal experience, occupational therapists need to consider the risks and opportunities of exploring new roles and maintaining existing services. PURPOSE: I propose three questions to guide the optimal positioning of occupational therapy services. First, how proximal is occupation in the role? Second, how strong is the evidence to support occupational therapy in the role? Third, is the timing right for change? These questions are applied to the role of occupational therapy in primary health care. KEY ISSUES: Occupation is proximal and the evidence is emerging to support an occupational therapy role in primary health care. Reforms make timing ideal. IMPLICATIONS: If we focus on the underlying principles of primary health care reform, the potential for an emerging role in primary health care is optimal. The same three questions can be used to transform and optimally position occupational therapy. PMID- 22043553 TI - [Critical analysis of ADL measuring instruments in pediatrics: executive deficits and independence]. AB - BACKGROUND: Although the assessment of the activities of daily living (ADL) through task analysis is central to the role of the occupational therapists working with children with traumatic brain injury (TBI), no review has revealed any study aimed at analyzing the instruments used to this effect, in regard to their potential to highlight the deficits associated with the executive functions (e.g., formulate a goal, planning). PURPOSE: To determine if any ADL assessment tools validated for children 10 to 15 years with a TBI consider executive functions. METHODS: Four tools, i.e., "Assessment of Motor and Process Skills' the "Children's Kitchen Task Assessment', the "Chocolate Cake Task" and the "ADL Profile' were analyzed according to the following criteria: 1) complexity of the tasks, 2) non-structured assessment method, and 3) psychometric properties appropriate for the target population. RESULTS: These tools are only partially consistent with the desired criteria. CONCLUSION: Further research on these tools will be necessary to meet the needs of this population. PMID- 22043554 TI - Strengthening the Kawa model: Japanese perspectives on person, occupation, and environment. AB - BACKGROUND: The Kawa model emerged to meet a need for occupational therapy models and theories relevant to Japanese clients and since its inception has evolved considerably. PURPOSE: To provide an overview of the Kawa model and to contribute to a critique of the model from Japanese perspectives on person, occupation, and environment. KEY ISSUES: The paper notes that the Kawa model does not portray inner self nor does it integrate one's active belonging; the author identifies the challenges of addressing issues related to occupations, and introduces the concept of seken (day-to-day community). IMPLICATIONS: The model would be strengthened by presenting inner self and a discrete layer of seken in the environment to effectively articulate belonging. The ways of presenting occupation need to be improved to capture relationships between occupation and belonging, effects of occupations, and positive and negative meanings attributed to an occupation. Exploring relationships between self occupation, life flow, and harmony is warranted. PMID- 22043555 TI - Brain injury from a first nations' perspective: teachings from elders and traditional healers. AB - BACKGROUND: There is a lack of knowledge about how cultural ideas affect First Nations peoples' perception of rehabilitation needs and the ability to access services. PURPOSE: The study explored the perceptions of treating and healing brain injury from First Nations elders and traditional healers in the communities served by Wassay-Gezhig-Na-Nahn-Dah-We-lgamig (Kenora Area Health Access Centre). METHODS: A participatory action approach was used, leading to a focus group with elders and traditional healers. Findings, established through a framework analysis method, were member checked prior to dissemination. FINDINGS: Four themes arose from the data: pervasiveness of spirituality, "fixing" illness or injury versus living with wellness, working together in treating brain injury, and financial support needed for traditional healing. IMPLICATIONS: Funding is required for traditional healing services to provide culturallysafe and responsive occupational therapy services to First Nations individuals with brain injury. PMID- 22043556 TI - A phenomenological inquiry into the embodied nature of occupation at end of life. AB - BACKGROUND: Occupational therapists propose that occupation is a basic human need across the lifespan. However, there is limited understanding of how occupation contributes to the end-of-life experience. PURPOSE: The purpose of this study was to examine the embodied nature of occupation at end of life from the perspectives of Canadians 60 years of age or older who are diagnosed with a terminal illness. METHODS: The study adopted a phenomenological methodological approach to conduct semi-structured interviews with eight participants. FINDINGS: Six themes were identified. Participants described orientations toward occupations that involved: living with death, reworking everyday life, being guided by the will of the body, giving priority to relationships, attending to the small things, and engaging existential orientations. IMPLICATIONS: This study contributes to knowledge about occupation at end of life and offers a starting point to guide practice that is attentive to the lived dimensions of occupation at end of life. PMID- 22043557 TI - Introducing the Leadership in Enabling Occupation (LEO) model. AB - BACKGROUND: Occupational therapy is a broad profession yet access to services remains restricted and uneven across Canada. Access to the potential breadth of occupational therapy is severely restrained by complex supply, retention, and funding challenges. To improve access to occupational therapy, widespread leadership is needed by all practitioners. PURPOSE: This brief report introduces the Leadership in Enabling Occupation (LEO) Model, which displays the inter relationship of four elements of everyday leadership as described in "Positioning Occupational Therapy for Leadership," Section IV, of Enabling Occupation II: Advancing a Vision of Health, Well-being and Justice through Occupation (Townsend & Polatajko, 2007). KEY ISSUES: All occupational therapists have the power to develop leadership capacity within and beyond designated leadership positions. IMPLICATIONS: LEO is a leadership tool to extend all occupational therapists' strategic use of scholarship, new accountability approaches, existing and new funding, and workforce planning to improve access to occupational therapy. PMID- 22043558 TI - Conceptualizing community development: occupational therapy practice at the intersection of health services and community. AB - BACKGROUND: Despite occupational therapy's theoretical commitment to community development (CD) approaches, current practice models focus on individual interventions rather than community issues. PURPOSE: This research examined three cases of Canadian occupational therapists working in CD to conceptualize CD from an occupational therapy perspective. METHOD: Data collection occurred over 12-14 days at each site and included observations, document reviews, and interviews with 14 colleagues and program participants. Constructivist grounded theory informed data analysis. FINDINGS: A conceptual framework was developed that describes the contextual background to CD initiatives and the strategies used: nurturing community partnerships, building community capacity, influencing health services, and linking sectors. Underlying these strategies was the strategic use of self which allowed the sharing of power and legitimacy to create opportunities for meaningful occupational engagement. IMPLICATIONS: The conceptual framework helps articulate CD's underlying processes and can be used to understand and guide practice. PMID- 22043559 TI - Prevalence trend of renal replacement therapy in Thailand: impact of health economics policy. AB - OBJECTIVE: The national health insurance fund in Thailand initiated by the national health security act in November, 2002. In October 2007, the national health insurance fund launched the first renal replacement therapy (RRT) reimbursement plan by the "Peritoneal Dialysis-First" (PD First) policy. The rationale of the PD First Policy resulted from the perspective that PD for end stage renal disease (ESRD) treatment offers the most economic and efficient outcome. The present study was conducted to determine whether the increase of RRT penetration by national health policy could impact the national RRT prevalence. MATERIAL AND METHOD: The Thailand Renal Replacement Therapy (TRT) database in 2007, 2008, and 2009 were retrieved and analyzed. RESULTS: By TRT registry data, the total yearly prevalence of RRT increased by an average of 14.8% after the implementation of national health insurance and the "PD First" policy from 2007 to 2009. The total yearly prevalence of hemodialaysis (HD) modestly increased (14.7%) while the total yearly prevalence of PD remarkably expanded by 107.3%. The yearly incidence of all RRT modalities increased by an average of 34.8% in 2007 to 2009. The yearly incidence of HD modestly increased (8.1%) while the total yearly incidence of PD remarkably elevated by 157.8%. Civil Servants Medical Benefit Compensation (CSMBS) was the major funding source of RRT cases (34.5%) while national health insurance funding was the second major funding source (26.0%). From 2007-2009, the CSMBS funding was the majority of HD while national health insurance funding was the majority of PD. The sharing of PD by national health insurance increased from 33.9% in 2007, 58.6% in 2208, and 77.2% in 2009. CONCLUSION: The coverage ofESRD patients by national health insurance fund by the "PD First" policy impacted the RRT prevalence and incidence both the total prevalence and total incidence due to the universal penetration to RRT treatment of Thai population. Also, the policy altered the RRT modality predisposition. PD modality willfinally be the majority ofThaiRRT modalities if the policy can be managed successfully. PMID- 22043560 TI - The incidence of peritoneal dialysis-related infection in Thailand: a nationwide survey. AB - OBJECTIVE: Implementation of the "Peritoneal Dialysis-First (PD First)" policy, mandating PD as the first modality of renal replacement therapy for end-stage renal disease patients under universal health coverage, leads to a rapid growth of PD cases and centers in Thailand. Since PD-related infection is the Achilles' heel of PD, this retrospective study was conducted to examine the magnitude of PD related infection in Thailand under the "PD First" policy. MATERIAL AND METHOD: All PD centers in Thailand were included in the present study. PD nurse specialists in each center were requested to review medical records of all patients undergoing PD during October 1, 2009 to September 30, 2010 and to submit data to the main investigators. RESULTS: Eighty-eight percent of all active PD centers in Thailand (102 out of 116) participated in the present study. One hundred and thirty-three nephrologists and 220 PD nurse specialists served 8,201 PD prevalent patients in these centers (7,925 CAPD and 276 APD). The overall exit site infection (ESI) rate was 1 episode/37.7 patient-month (0.32 episodes/patient year) while the overall peritonitis rate was 1 episode/25.5 patient-month (0.47 episode/patient-year). CONCLUSION: Despite the rapid growth of PD cases under the limited resource, the PD-related infection rates in Thailand are only small degree behind the goal of Asia-Pacific Key Performance Indicators (KPIs) Task Force. PMID- 22043561 TI - From the "PD First" policy to the innovation in PD care. AB - OBJECTIVE: Due to the rapid growth of peritoneal dialysis (PD) program under the "PD First" policy of Thailand, it is necessary to have many voluntary well training PD staffs and a good education program for PD nurses to serve an excellent PD outcome. In the present study novel devices, which could be practically used in PD patients, were developed by the creative PD trainee idea of to facilitate PD self-care and decrease work load of PD staffs. MATERIAL AND METHOD: Young PD nurses in the 3rd generation of PD trainee program from King Chulalongkorn Memorial Hospital were assigned to develop novel tools in order to assisting patient care in real practice. The efficacy of these inventions and patient satisfaction were assessed by comparing with the standard method. RESULTS: The authors presented two interesting innovations in the present study. The first one, "Troubleshooting Wheel", contained six common complaints and the advice for correcting each problem in the platform of rotating wheel. Participants could solve problems more rapidly than using the standard handbook for PD (p < 0.01) and also found the correct responses more frequently than the handbook (p < 0.01). The second one, "Exit Site Abacus", the sliding platform with automatic calculation of the sum of exit site score, was the easier method in evaluating the exit site infection than the conventional exit site scoring using the Prowant's table or their own memory. CONCLUSION: Reinforcement of the development of PD nursing program not only increases the number of PD staffs but also contributes to the innovations for improving quality of PD care by the young new staffs. PMID- 22043562 TI - Prevalence and factors affecting peritonitis in CAPD patients in Maharat Nakhon Ratchasima Hospital under universal coverage scheme during 2008-2010: a three year experience. AB - OBJECTIVE: Since 2008, the Thai government has subsidized the package to cover chronic ambulatory peritoneal dialysis (CAPD) for end stage renal disease (ESRD) patients under the universal coverage scheme (UCS) in Thailand. The aim of the program is to keep longer life in poor people instead of death due to inaccessibility to renal replacement therapy as usual. The present study was conducted to evaluate the prevalence and factors affecting peritonitis in patients with CAPD therapy under the UCS at Renal unit, Maharat Nakhon Ratchasima Hospital, during January 1, 2008-December 31, 2010. MATERIAL AND METHOD: Medical records of ESRD patients undergoing CAPD under UCS at Maharat Nakhon Ratchasima Hospital during January 1, 2008-December 31, 2010 were reviewed. The collected data included demographic details, underlying diseases, body mass index (BMI), laboratory findings, peritonitis rate, and outcome of therapy at December 31, 2010. RESULTS: There were 318 ESRD patients with the mean age of 49.9 +/- 14.3 years and mean BMI of 23.1 +/- 3.9 kg/m2. The common causes of ESRD were hypertension (60.1%) and diabetes mellitus (34.9%). In the follow-up period, 318 patients received the treatment over a total observation period of 3,262.2 patient-months. The patient survival was 51.0% at 3 years. Most of the patients (74.8%) had no peritonitis. There were 128 peritonitis episodes. The mean duration from starting CAPD to the first episode of peritonitis was 25.5 patient months per episode. Staphylococcus spp. was the most common organism causing peritonitis which is the major cause of technical failure. The factors affecting peritonitis is included age > 60 years, hypokalemia (< 3.5 mEq/L), and hypoalbuminemia (< 3.5 g/dl). CONCLUSION: To improve clinical outcome of CAPD patients by decreasing the peritonitis rate, the factors affecting peritonitis should be corrected. The patients and care-givers should also be educated about the importance of hygiene and exchanging methods to decrease the peritonitis rate in CAPD patients. PMID- 22043563 TI - Peritonitis in peritoneal dialysis patients: Ramathibodi Hospital experience. AB - OBJECTIVE: This single center retrospective cohort study was conducted to assess peritonitis rate during 2000 to 2010. MATERIAL AND METHOD: All 103 peritoneal dialysis (PD) patients during January 2000 to December 2010 were recruited in the present study. RESULTS: There were 112 episodes ofperitonitis during 5,238 patient-month which was 1 episode ofperitonitis in 46.77 patient-month or 0.257 episode per patient-year. Fifty-eight patients used the previous single bag dialysis solution (both safe lock and spike system). During 2003-2005, 35 (60%) patients who previously used the single bag system were retrained and changed to new double bags connecting system while the remainings were out of program before this system was available in the hospital. After the new double bags connecting systems and automated peritoneal dialysis (APD) were available, 71 and 7 new patients were commenced on double bags system andAPD respectively. The authors found 66 peritonitis during 2,686 months in the group of patients who used single bag solution which was equall to 1 episode of peritonitis in 40.70 patient-months or 0.295 peritonitis per patient-year. In the double bags solution group, there were 45 episodes of peritonitis during 2,722 months which equalled 1 peritonitis in 60.49 patient-months or 0.198 peritonitis per patient-year, while the authors found I episode of peritonitis in 88 patient-month or 0.136 peritonitis per patient-year. In the present study, there were 38 (36.9%) diabetic patients. There were 35 and 77 episodes of peritonitis within 1,141 and 4,355patient-months which means 1 episode of peritonitis every 32.60 and 56.56 months or 0.368 and 0.212 peritonitis perpatient-year in diabetic and non diabetic patients respectively. CONCLUSION: The authors confirmed that diabetes mellitus was the risk factor of peritonitis in the authors unit. With the new double bags connecting system and APD, peritonitis rate in the authors unit decreased significantly. Peritonitis rate in the authors unit was 0.257 episode per patient year or 1 episode every 46.77 patient-months which achieved the goal standard. PMID- 22043564 TI - A single-centre experience: peritoneal dialysis-related infections in patients on long-term dialysis. AB - OBJECTIVE: Peritoneal dialysis is a convenient way of maintaining patients with end stage renal disease (ESRD) and in the present days, the Thai government supports all payments for ESRD patients. Continuous ambulatory peritoneal dialysis-(CAPD) related infections are the major cause of morbidity and mortality. The present study was conducted to identify the incidence and epidemiological data of CAPD-related infection. MATERIAL AND METHOD: Medical records of 333 CAPD patients attending the Dialysis Unit of Phramongkutklao Hospital from January 1983 to June 2007 were reviewed. The historical cohort study was focused on the incidence of CAPD-related infections, causing pathogens, risk factors, and patient outcome. RESULTS: In total, 73.3% of episodes developed peritoneal infection. The incidences of peritonitis, exit site infection, and tunnel infection were 0.864, 0.213, and 0.034 episodes per patient per year, respectively. The most common infecting organisms were gram positive cocci (49.1%). The main pathogens were Coagulase-negative staphylococcus (15.9%), Staphylococcus aureus (15.2%) and Pseudomonas spp. (14.2%). CAPD-related infections increased in patients who had age > 60. A total of 81% of the infections responded to initial antibiotic therapy administered in the dialysis fluid. Overall, there were 10 episodes (1.9%) of the refractory group and 83 episodes (15.4%) of peritoneal catheter loss, with an overall mortality rate of 1.1%. Non-vancomycin based regimens were applied in 63.9% of peritoneal infected patients. CONCLUSION: The authors' center's CAPD-related infection rate achieved the International Society for Peritoneal Dialysis (ISPD) recommendation. A significantly enhanced incidence of CAPD-related infection occurred in advanced age. Coagulase-negative staphylococcus is still a very common organism that generally responds well to antibiotic therapy. PMID- 22043565 TI - Risk factors of infectious peritonitis of CAPD patients in Rajavithi Hospital. AB - OBJECTIVE: Continuous ambulatory peritoneal dialysis (CAPD) is a renal replacement therapy for end stage renal disease (ESRD) patients. Peritoneal infection, peritonitis is a major cause of death and technical failure in ESRD patients receiving CAPD treatment. Previous studies demonstrated that lower serum albumin, higher body mass index, and diabetic kidney disease were associated with increase in incidence of peritonitis. However the demographics of the patients in the Rajavithi hospital such as race, gender, age, socioeconomic status and various other factors were different from the patients in the previous studies. The present study was conducted to investigate the risk factors of peritonitis, causative organisms, and route of infection among CAPD patients in Rajavithi Hospital. MATERIAL AND METHOD: This is a retrospective descriptive study. All patients in the present study are ESRD patients who received CAPD treatment during March 2009 to February 2011 and adhered with the treatment for at least 1 year. The patients were divided into two groups 1) the patients who got infectious peritonitis within 1 year after catheter implantation and 2) the patients who did not get or got infectious peritonitis after 1 years. The medical records were reviewed and the data were analyzed to identify the risk factors of peritonitis, frequency of causative organisms, and the route of infection. RESULTS: Of 27 patients, 16 patients (59.3%) had peritonitis within the first year, and 11 patients (40.7%) had no peritonitis or had peritonitis after the first year. The risk factors associated with peritonitis were diabetes (62.5 % in patients with peritonitis within first year vs. 18.2% in the patients who had no peritonitis or had peritonitis after the first year, p = 0.047) and higher blood sugar level (139.5 +/- 34.6 mg/dl in patients with peritonitis within first year vs. 115.9 +/- 23.4 mg/dl 18.2% in the patients who had no peritonitis or had peritonitis after the first year, p = 0.011). Transluminal peritoneal catheter route was the route of infection in every subject in the present study. The major causative agents were gram-positive bacteria. CONCLUSION: Diabetic kidney disease and high fasting blood sugar were the risk factors of peritonitis and trans luminal peritoneal catheter are the major route of infection in the present study. Therefore, good blood sugar control and strict adherence with sterile technique for peritoneal dialysis would decrease the incidence of peritonitis in CAPD patients. PMID- 22043566 TI - The changing profile of PD-related peritonitis in Thailand: a single centers experience. AB - OBJECTIVE: The percentage of utilizing peritoneal dialysis (PD) in Thailand was increased dramatically since the implementation of PD-First policy in 2008. However, peritonitis remains a major obstacle to achieve success of this modality. The aim of the present study, was to assess the clinical characteristics of PD peritonitis in the PD-first policy era. MATERIAL AND METHOD: The PD peritonitis patients in Bhumibol Adulyadej Hospital between October 2008 and December 2010 were reviewed. Microbiological diagnosis, treatment responses, technique, and patient survival were analyzed. RESULTS: Since October 2008, 93 peritoneal dialysis patients were followed-up in Bhumibol Adulyadej Hospital including 75 new cases. During the present study period of 1,560 patient-months, 51 episodes of peritonitis from 33 cases were recorded and analyzed. The mean age of the peritonitis patients was 57.9 +/- 16.1 years and 63.6% were females. The most common isolates were gram negative organisms (33.3%) followed by gram positive (17.6%) and fungi (5.9%). Nocardiosis was diagnosed in 1 patient. However, 43.1% of episodes were culture-negative peritonitis. Treatment of peritonitis resulted in a complete cure in 74.5% of patients while 7.8% of patients required catheter removal, and 17.6% died. Event-free survival was better in gram positive organisms (43.3 months) compared with those infected with gram negative (26.8 months) and culture negative peritonitis (16.1 months). CONCLUSION: The proportions of peritonitis due to gram negative organisms were increased and associated with less favorable outcome. These findings suggest that it is necessary to prepare the appropriate protocol for prevention and treatment of PD peritonitis under national PD-First policy scheme. PMID- 22043567 TI - The effects of peritoneal dialysis catheter insertion using paramedian versus midline approach on CAPD patients. AB - OBJECTIVE: Types of peritoneal dialysis (PD) catheter design and catheter insertion techniques have been shown to affect catheter-associated infection, catheter survival, as well as, overall patient survival. Thus far, there have been no studies demonstrating a difference in long term outcome between two insertion techniques used for PD placement, including midline and paramedian incisions. The present study was conducted to compare clinical outcomes among CAPD patients who had bedside PD catheter insertion through midline incision vs. paramedian incision in terms of early post-operative complications and long term outcomes. MATERIAL AND METHOD: This is a retrospective study. All CAPD patients who received treatments at Maharat Nakhonratchasima Hospital during the year 2008 2010 were included in the present study. Age, sex, co-morbid diseases, laboratory results obtained prior to dialysis, early post-operative complications, and late post-operative complications were documented. RESULTS: A total of 392 patients were identified. Of these, 43 patients were excluded due to incomplete medical records. The remaining 349 cases were collected for analysis, 90 cases having paramedian incision and 259 cases having midline incision. The average age was 51.7 years old, and 52% were male. The baseline characteristics and patient parameters were similar in both approaches. The paramedian group was found to have lesser early post-operative complications (7.78%) when compared to the midline group (18.82%) (p = 0.02). Moreover, the long term outcomes were shown to be greater in paramedian approach when compared to the midline group in terms of PD catheter survival (985.5 vs. 698.1 days, p = 0.048) and overall patient survival (915.4 vs. 700.6 days, p = 0.01). However, there was no significant difference in peritonitis-free survival (848.7 vs. 824.3 days, p = 0.93). CONCLUSION: Comparing PD catheter insertion using paramedian incision with midline incision, paramedian incision was associated with less early post operative complications, more prolonged PD catheter survival and better overall patient survival. Therefore, paramedian incision should be recommended as the preferred method for PD catheter insertion. PMID- 22043568 TI - Experiences on bedside Tenckhoff catheter implantation. AB - OBJECTIVE: To clarify the outcome of a bedside technique of peritoneal dialysis (PD) catheter implantation which is practiced differently from worldwide guidelines in some points. MATERIAL AND METHOD: This retrospective study was conducted in end stage renal diseases (ESRD) patients treated with chronic ambulatory peritoneal dialysis (CAPD). Catheter placement was initiated by the authors' bedside technique comprising no antibiotic prophylaxis, dry abdomen, and routinely right sided exit site as our protocol. All events within one month postimplantation, such as tip mal-position, malfunction, infection, and bleeding were analyzed. RESULTS: One hundred and fourteen cases were participated with age, ranged from 14 to 78 yrs. Of the participating subjects, 38.5% was female and 60.52% was diabetes mellitus (DM). After 1 month, 113 out of 114 cases (99.1 %) accomplished CAPD. Of these, 79.8 % had good tip position and function after the break-in period. Early mal-position and poor flow was detected in 21 cases (18.4 %); 9 of them responded to laxative bowel stimulation while 12 cases needed surgical correction. Exit-site infection and/or wound infection were found in 7.9%. The peritonitis rate was 2.63%. All cases with infection were cured. Coagulase positive Staphylococcus aureus was the major causative organism. CONCLUSION: Bedside Tenckhoff catheter implantation without antibiotic prophylaxis in dry abdomen is a safe modality for selected ESRD patients. PMID- 22043569 TI - Does previous abdominal operation affect peritoneal dialysis complications and outcomes? AB - OBJECTIVE: Peritoneal dialysis (PD) "First Policy" for end stage renal disease (ESRD) patients who are under universal healthcare coverage scheme, was implemented in Thailand since January 2008. Now there are about 10,000 PD patients all over the country and most of them are in low to medium socio economic status. In the past, previous abdominal operation was considered as a contra-indication to PD. The purpose of the present study is to compare the complications and outcomes between patients with and without previous abdominal operation. MATERIAL AND METHOD: The present study was a retrospective review of all new PD cases for complications and outcome of the first PD catheter implantation. The method of catheter implantation is mini-laparotomy under local anesthesia by one surgeon. The bleeding, exit site/wound infection, catheter malposition/obstruction, and catheter/technique/patient survival rate were compared between two groups. RESULTS: In 730 ESRD patients who underwent catheter implantation, there were 106 patients with history of previous abdominal operation (14.5%). There were no significant differences between patients "with previous abdominal operation" and "without previous abdominal operation", for bleeding, exit site/wound infection, catheter malposition/obstruction, and catheter/technique/patient survival. CONCLUSION: History of previous abdominal operation in ESRD patients is not a contra-indication to PD. The complications are low and the outcomes are excellent regardless of previous abdominal operation. Dedicated catheter implantation team might be the key of success. PMID- 22043570 TI - The technique and outcome of peritoneal dialysis catheter revision. AB - OBJECTIVE: Tenchkhoff catheter malposition is a significant cause of technical failure in patients with peritoneal dialysis (PD). Many surgical revised techniques have been reported including wire manipulation and laparoscopy. The objective of the present study was to report the outcome of surgical revised technique for catheter malposition in patients with PD. MATERIAL AND METHOD: The data of one hundred and twenty three patients with peritoneal dialysis at the HRH Princess Maha Chakri Sirindhorn Medical Center were reviewed. The Tenchkhoff catheters were revised in ten patients who had delayed outflow drainage and failed with nonsurgical treatment. The outcome of catheter placement and revision were reported. RESULTS: The longest catheter survival time in the authors' patient was 71 months. The Tenchkhoff catheters were revised successfully in ten patients. The positions of exit sites were not changed. The immediate postoperative complication was not found. The second revision of Tenchkhoff catheter was performed in three patients. Five patients died from other causes not related to the catheter malposition, one patient was referred to another hospital, and four patients had still undergone CAPD. CONCLUSION: The authors catheter-revised technique is safe, simple, straightforward and no special instrument needed therefore it is suitable to be practiced in Thailand. PMID- 22043571 TI - Comparison of the Seldinger technique and surgical technique in Tenckhoff catheter insertion in CAPD patients: a single center experience. AB - OBJECTIVE: To compare clinical outcomes of catheter placement between surgical technique and Seldinger technique, including catheter survival and early post operative complications. MATERIAL AND METHOD: This retrospective study was conducted in Maharaj Nakhon Si Thammarat Hospital, a tertiary-center hospital in southern part of Thailand. Three-year data, during October 2007-2010, were retrieved from medical records and hospital database. Early post-operative complications, including major bleeding, peritoneal leakage, and peritonitis rate, and long-term outcome were assessed. RESULTS: One hundred forty-nine and 56 out of 205 patients were inserted Tenckhoff catheter by surgical technique and Seldinger technique, accordingly. The average age was 49.8 years old. Sixty percent of them were male. Neither of early postoperative complication and long term outcome was found to have significant difference. However, patients with surgical technique received more topical antibiotic [15 (10.0%) vs. 0 (0%), p = 0.014] and trended to have more episode of early postoperative peritonitis [15 (10.1%) vs. 3 (5.4%)p = 0.288]. CONCLUSION: Although Seldinger technique is more feasible for practical nephrologists and less time consumption; the success, early post-operative complications, and long term outcome are comparable with surgical technique. The surgeons or nephrologists who perform catheter placement should be aware of catheter-related infection, especially in the first few weeks. PMID- 22043572 TI - Determination of peritoneal membrane transport characteristics with dialysis adequacy and transport test in Thai patients. AB - OBJECTIVE: The characteristics of peritoneal membrane transport are useful for the determination of dialysis treatment prescription. The peritoneal equilibration test (PET) is accepted as a gold standard tool for identification of these characteristics. Unfortunately, the process of PET is troublesome and unsuitable for clinical practice. Dialysis adequacy and transport test (DATT), which is easier and more convenient method, is proposed as an alternative test. The aim of the present study was to evaluate the accuracy of the DATT in determination of membrane characteristics in Thai patients. MATERIAL AND METHOD: Fifteen patients underwent both DATT and PET on the same day. The second DATT was performed. The 24-hour dialysate-to-plasma ratio of creatinine (D/Pcr) from each DATT was compared with the adjusted 4-hour D/Pcr from the corresponding PET. The types of membrane solute transport were classified using the PET proposed by Twardowski and the DATT suggested by Rocco into high, high average, low average, and low transporter RESULTS: The mean age was 48.1 +/- 16.4 years. The mean value of D/Pcr derived from DATT was higher than PET (0.80 +/- 0.10 vs. 0.74 +/- 0.14). The results of both D/Pcr were correlated (r = 0.78, p = 0.001). However, determinations of characteristics of membrane transport were discordant (kappa coefficient = 0.25). The results of the repeated D/Pcr were not different and the classification of membrane transport properties were concordant (kappa coefficient = 0.68). CONCLUSION: The results of D/Pcr derived from both tests were correlated. However determinations of characteristics of membrane transport were discordant. PMID- 22043573 TI - Insulin resistance in dialysis versus non dialysis end stage renal disease patients without diabetes. AB - OBJECTIVE: Insulin resistance is frequently recognized in uremic patients and is a predictor of cardiovascular mortality in end stage renal disease (ESRD) patients. However sparse data are available regarding the effects of different methods of renal dialysis on insulin resistance in ESRD without diabetes. The present study was conducted to evaluate the levels of insulin resistance in dialysis versus non dialysis ESRD patients without diabetes. MATERIAL AND METHOD: A cross-sectional study was carried out in 45 non diabetic ESRD patients including continuous ambulatory peritoneal dialysis (CAPD), hemodialysis (HD), and non dialysis ESRD patients. The value of insulin resistance was obtained by homeostasis model assessment (HOMA). Estimation of the glomerular filtration rate (GFR) was obtained by the four-variable Modification of Diet in Renal Disease equation and ESRD was defined when GFR was below 15 ml/min/1.73 m2. RESULTS: Non diabetic ESRD patients were studied: 12 patients on CAPD treatment for 67.4 months, 18 patients on HD treatment for 89.3 months, and 15 patients on conservative treatment. HOMA scores (CAPD 5.4 +/- 2.3, HD 6.0 +/- 1.9 vs. non dialysis 1.5 +/- 0.9, p < 0.05) and fasting plasma insulin levels (CAPD 21.9 +/- 7.7 microU/mL, HD 19.5 +/- 8.4 microU/mL vs. non dialysis 4.4 +/- 2.5 microU/mL, p < 0.05) of the CAPD and HD groups were significantly higher than the non dialysis ESRD group, with no significant differences observed between CAPD and HD groups. However, fasting plasma glucose was significantly lower in the HD group than the CAPD and non dialysis ESRD groups (CAPD 98.2 +/- 10.6 mg/dL, non dialysis 93.0 +/- 11.5 mg/dL vs. HD 76.2 +/- 7.8 mg/dL, p < 0.05). All groups showed no significant differences for blood pressure, body weight, body mass index, fat free mass, body fat, and serum levels of albumin, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. CONCLUSION: Impaired insulin sensitivity in both dialysis groups after long term dialysis was still higher than that of the non dialysis ESRD group. However, no significant differences were noted between CAPD and HD treatments. PMID- 22043574 TI - Relationship between malnutrition-inflammation syndrome and ultrafiltration volume in continuous ambulatory peritoneal dialysis patients. AB - OBJECTIVE: Malnutrition inflammation syndrome may contribute to a change of peritoneum, leading to high peritoneal membrane transport, peritoneal albumin loss, and increased glucose uptake into systemic circulation and decreased ultrafiltration (UF) volume. Fluid overload is a common problem among CAPD patients which has an effect on morbidity and mortality in these patients. The present study was designed as a pilot to find out a correlation between malnutrition and UF volume in CAPD patients. MATERIAL AND METHOD: A cross sectional study was comducted in 42 stable CAPD cases at CAPD clinic, Maharaj Chiang Mai Hospital. Subjective global assessment score (SGA), malnutrition inflammation score (MIS), and laboratory values were utilized to identify nutritional and inflammatory status. Peritoneal equilibration test (PET) was performed to measure UF volume while bioelectrical impedance assay was determined to measure extracellular fluid volume (ECF), lean body mass (LBM), lean fat mass, and fluid status. RESULTS: Of 42 CAPD patients, 30 subjects were classified to have normal nutritional status while 12 patients were categorized to have malnutrition. Only 1 patient was classified to have malnutrition inflammation syndrome. MIS scores and serum albumin were significantly different between 2 groups (p < 0.001). PET-UF volume was significantly decreased in the malnutrition group (p < 0.05), especially when serum albumin was less than 3.0 g/dl. PET-UF volume was reduced 137.44 ml for every 1 g/dl of serum albumin below 3.0 g/dl. Residual renal function (RRF) was also significantly reduced in malnutrition group (p < 0.05). Malnutrition, decreased RRF and decreased UF volume led to ECF expansion, hypertension, and fluid overload. Other factors that were correlated with UF volume were ACEI and/or ARB use (p < 0.05) and total protein loss per day (p < 0.05). CONCLUSION: There was a significantly positive correlation between malnutrition and reduction of UF volume. Other factors that were correlated with UF volume were ACEI and/or ARBS use and total protein loss per day. PMID- 22043575 TI - Secondary hyperparathyroidism and risk factors in patients undergoing peritoneal dialysis in a tertiary hospital. AB - OBJECTIVE: Secondary hyperparathyroidism (SHPT) can lead to significant morbidity, mortality, and additional healthcare resource utilization in chronic kidney disease. Since the introduction of continuous ambulatory peritoneal dialysis (CAPD) policy for end stage renal disease patients in Thailand, no large studies have been conducted to examine parathyroid dysfunction in these patients. The baseline prevalence data are highly required. The present study was conducted to determine the prevalence of SHPT and the risk factors associated with this dysfunction in CAPD patients. MATERIAL AND METHOD: The authors analyzed data of 173 patients who received CAPD at a single center between October 2008 and October 2010. Clinical data and laboratory variables related to parathyroid function were obtained from each patient. Hyperparathyroidism was diagnosed when serum intact parathyroid hormone (iPTH) level was above 300 pg/ml. Variables predicting the development of hyperparathyroidism were calculated by univariate and multivariate logistic regression analysis. RESULTS: Hyperparathyroidism was identified in 29.48% of the CAPD patients. Significantly lower serum calcium levels (p = 0.037), significantly higher serum phosphate levels (p = 0.016) and significantly greater serum alkaline phosphatase concentrations (p = 0.029) were observed in the patients with hyperparathyroidism. By multiple regression analysis, the duration on CAPD showed a significant positive correlation with iPTH (r = 0.359, p < 0.01) while the total corrected Ca levels had a significant negative correlation with iPTH (r = -0.176, p = 0.023). CONCLUSION: There is a high prevalence of hyperparathyroidism in the current Thai CAPD population. Duration on CAPD and hypocalcemia are independent risk factors for the development of hyperparathyroidism. PMID- 22043576 TI - Oral and radiographic findings in patients undergoing continuous ambulatory peritoneal dialysis. AB - OBJECTIVE: To compare the oral status, cortical and spongy bone density of the mandible, and dental pulp calcification between the patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and age- and sex-matched healthy controls. MATERIAL AND METHOD: Thirteen end stage renal disease patients undergoing CAPD and 17 age- and sex- matched healthy volunteers were enrolled. The questionnaires, oral radiography, and intraoral examination, including number of decayed teeth, filled teeth, missing teeth, plaque index, gingival index, calculus index, and oral hygiene index were performed in both groups. Two views of oral radiology, comprising panoramic and bite-wing radiographs, were taken to evaluate mandibular bone density and pulp calcification. The data were analyzed with t-test and Mann-Whitney U tests. RESULTS: Both groups were similar in baseline demographics, including age, sex, and education. Plaque index, calculus index, and oral hygiene index of the CAPD patients were significantly worse than the controls' (p = 0.025, 0.015, and 0.014, respectively). Percentage of decayed teeth and missing teeth of the CAPD patients had a trend to be higher than control. The percentage of filled teeth, decayed missing filling tooth (DMFT) index, sum of percentage DMFT, gingival index, average of spongy and cortical bone densities, and the percentage of pulp calcification were comparable in both groups. CONCLUSION: CAPD had poorer oral hygiene than the healthy; however; DMFT pulp calcification, and bone density were not differenct from the healthy. This urges the medical personnel to examine all CAPD patients in order to prevent hematogenous spreading of occult oral infection. PMID- 22043577 TI - Health promotion behaviors and related factors in end stage renal disease patients treated with continuous ambulatory peritoneal dialysis. AB - OBJECTIVE: To present study health promotion behaviors and related factors in end stage renal disease (ESRD) patients treated with continuous ambulatory peritoneal dialysis (CAPD). MATERIAL AND METHOD: Questionnaires of Pender to evaluate health promotion behaviors which measure 5 aspects of health-affected behaviors were examined in 90 CAPD patients at dialysis unit of Udornthani Hospital. Results were categorized into 3 groups according to Bloom's scale as follows: high, moderate, and low levels. The data were displayed as ranges or means +/- standard deviation, according to the characteristics of each variable, with a 5% (p < 0.05) significant level. For nonparametric variables, comparisons were conducted by using the Chi-square and Fisher exact tests. Pearson correlation test was utilized for statistical analysis where appropriate. RESULTS: Three fourths of the participants had high overall and individual rating of health promotion behaviors, including health responsibility, interpersonal relationship, spiritual improvement, and stress management behaviors. However, the behaviors related to personal activities and nutrition fell into moderate category. Of interest, none of patients had low overall rating. To assess influence factors on health promotion behaviors, only perception of health care promotion usefulness, perception of health care promotion obstacle, perception of themselves, and social support were related to the health promotion behaviors (r = 0.35, 0.34, 0.44, and 0.45, respectively; individual p-value was less than 0.01). Caregiver also influenced with lower degree correlation compared to the above factors. Neither demographics nor patient characteristics affected the behaviors. CONCLUSION: The results encourage efforts to monitor and detect health behaviors that might impair compliance with PD system. The center should find tailor-made strategy with assistance and supports by local community and family member to continuously promote and cherish health behaviors of the patients. PMID- 22043578 TI - Exfoliated mesothelial cell and CA-125 in automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) patients. AB - OBJECTIVE: Automated peritoneal dialysis (APD) becomes the first option for peritoneal dialysis, nowadays overtaking continuous ambulatory peritoneal dialysis (CAPD) in many countries. The comparison of peritoneal membrane alteration in CAPD and APD is inconclusive. The authors therefore compared the peritoneal membrane changes in patients undergoing CAPD and APD. MATERIAL AND METHOD: In naive end stage renal disease patients, the choice of PD modes (CAPD or APD) was dependent on the patient's decision. Thirty-six CAPD and 25APD patients with a total of 287 patient-months were compared. The peritoneal mass parameter, exfoliated mesothelial cell (MTC) and dialysate CA-125, as well as modified peritoneal equilibrium test (mPET) with 4.25% dextrose solution was simultaneously evaluated at 1 and 6 month follow-up. RESULTS: Although the peritoneal function (as measured by D/P creatinine, D/D0 glucose, sodium dipping, and dialysate protein loss), adequacy, serum albumin, nutritional status, and residual renal function showed no significant differences between groups at 1 and 6 months, CA-125 but not MTC was higher in APD compared with CAPD at the first month of PD beginning. Due to the single time-point measurement limitation, the authors compared the peritoneal mass parameter differences between 1 and 6 month. During 6-month follow-up, CA-125 decreased 30 +/- 5% vs. 7 +/- 5% and MTC decreased 5 +/- 12% vs. 40 +/- 11% in APD and CAPD, respectively. The higher CA 125 reduction in APD and greater changes of MTC in CAPD suggested that there was less viable mesothelial cell in APD compared with CAPD. CONCLUSION: The authors observed that both APD and CAPD damaged peritoneum. However, there might be higher peritoneal injury in APD patients. The proper randomization study in longer follow-up period is mandatory to confirm this observation. PMID- 22043579 TI - Intermittent peritoneal dialysis in acute kidney injury. AB - OBJECTIVE: The mortality rate of acute kidney injury (AKI) patients is high despite of new advanced continuous renal replacement therapy (CRRT), which has widely become the treatment of choice in patients who are hemodynamically unstable. Nevertheless, the effectiveness of CRRT in improving the survival outcome is still unclear. Therefore, many centers still use intermittent peritoneal dialysis (IPD) or intermittent hemodialysis (IHD) in hospital where CRRT is unavailable. The present study was carried out to evaluate outcome of AKI patients who were treated with IHD and IPD in Saraburi Hospital. MATERIAL AND METHOD: A retrospective study of AKI patients requiring dialysis during 2004 to 2009 was conducted. Patients who were under 15 years old or underwent more than one modality of dialysis were excluded. Demographic data and mode of RRT were analyzed for survival. RESULTS: Of all 145 patients, 101 were admitted into ICU. Mean age of patients was 61.6 +/- 17.8 years and 60.7% of all patients were male. Acute tubular necrosis was the most common cause of AKI, whereas volume overload was the leading indication for RRT. Overall mortality was 68.3%. There was no statistically significant difference in mortality rate between the two modes of dialysis. CONCLUSION: The mortality rate of AKI patients is high despite having dialysis support. There is no statistically significant difference in mortality rate between IHD and IPD among these patients. PMID- 22043580 TI - The glucose interference in creatinine measurement using an enzymatic method: effect of creatinine concentrations. AB - OBJECTIVE: To evaluate the influence of glucose and creatinine concentrations on the determination of creatinine by Jaffe picrate reaction and specific enzymatic assay. MATERIAL AND METHOD: Unused dialysate with 4.25% dextrose was diluted to obtain seven glucose concentrations. Two series of dialysate were spiked with creatinine to yield concentrations of 5 and 10 mg/dl. Creatinine measurements were obtained by Jaffe method and enzymatic assay. RESULTS: In unused dialysate solution with glucose concentrations from 559 to 4,250 mg/dl, the creatinine values obtained by the Jaffe method were higher than the enzymatic assay (0.31 +/ 0.20 vs. 0.08 +/- 0.01 mg/dl, p < 0.05). The correlation coefficient between glucose and creatinine from the Jaffe method were 0.98 (p < 0.001) but showed no correlation with creatinine measured with the enzymatic assay. On the other hand, the mean values of creatinine in dialysate with creatinine concentrations of 5 and 10 mg/dl derived by Jaffe method were lower than enzymatic assay (5.74 +/- 0.12 vs. 6.16 +/- 0.36 mg/ dl and 11.56 +/- 0.17 vs. 12.69 +/- 0.66 mg/dl, respectively). At creatinine concentration of 10 mg/dl, the correlation between glucose concentration and creatinine from enzymatic assay was significant. In contrast, at creatinine concentration of 5 mg/ dl, the correlations obtained from both methods were significant. CONCLUSION: The patterns of glucose interference with creatinine obtained from Jaffe method and enzymatic assay were quite different. The magnitude of interference with enzymatic assay was greater at a higher creatinine concentration. Therefore, the enzymatic assay might not be appropriate for creatinine measurement in patients using dialysate with dextrose 4.25% and membrane characteristic of high solute transporter. PMID- 22043581 TI - Correction formula for creatinine concentration with glucose in dialysate. AB - OBJECTIVE: Previous studies showed that high glucose in dialysate could interfere with creatinine measurement. This error might produce some mistakes in peritoneal dialysis (PD) treatment. The correction of creatinine is essentially needed. MATERIAL AND METHOD: Creatinine powder diluted in 0.1 N HCl was used as the standard reference. Different creatinine measurements obtained from unused dialysate solutions in various glucose concentrations were performed. Creatinine correction was performed by Twardowski's formula which was recommended by Nephrology Society of Thailand and by Tam's formula which utilized unused dialysate creatinine and glucose ratio. Comparison of the results in determination of membrane transport characteristics was based on the criteria proposed by Twardowski et al in used dialysate solutions derived from 17 CAPD patients with different approaches. RESULTS: The mean creatinine concentrations obtained from the standard creatinine solution and the above two correction methods were different. The mean creatinine derived from Twardowski's formula was the lowest. The correlation coefficients between glucose and creatinine interference obtained by direct measurement and by Twardowski's formula were high (r = 0.80-0.98) at all creatinine levels. However, the correlation between glucose and creatinine interference were significant only at creatinine concentrations of 2.9 and 17.5 mg%. Classification of membrane transport was discordant when different correction formulae were used. CONCLUSION: Creatinine correction in dialysate was crucial. Creatinine correction with fresh dialysate creatinine and glucose ratio might be suitable in clinical practice. PMID- 22043582 TI - The in vitro toxicity of peritoneal dialysis fluid. AB - OBJECTIVE: To investigate the toxicity of peritoneal dialysis fluid (PDF) components on peritoneal changes in primary human mesothelial cell. MATERIAL AND METHOD: To investigate the mechanism of changes, primary human peritoneal mesothelial cells (HPMCs) were isolated from human omental tissue and were exposed for 15 hours with the various concentrations of conventional PDF and various PDF components. The mesothelial injury was determined by calculating a ratio of supernatant and total intracellular LDH while mesothelial apoptosis was assessed and counted by positive TUNEL staining and flow cytometry, respectively. RESULTS: PDF caused mesothelial detachment, de-differentiation, cell injuries, and apoptosis and this depended on the concentrations of PDF. The acidic condition and high glucose concentration likely played a major role in the HPMC injuries and detachment while individual PDF component could not yield mesothelial apoptosis as severe as the whole PDF effects. Thus, the additive effects of PDF composition, instead of the effect of each component, contributed to dialysis-related HPMC damages. CONCLUSION: PDF showed concentration dependent fashion-induced HPMC injury, dedifferentiation, and apoptosis. All of the abnormalities occurred by the additive effects of PDF components. PMID- 22043583 TI - Hypercalcemia and refractory peritonitis alert the condition of tuberculous peritonitis: a case report and review literature. AB - Hypercalcemia is commonly encountered in peritoneal dialysis patients with parathyroid hormone abnormalities; however, most of them have faint clinical manifestation and the level usually is less than 13 mg/dL. If severe hypercalcemia exists, granulomatous infection and occult malignancy should be of concern. Tuberculosis, a granulomatous disease associated with hypercalcemia, is commonly prevalent in dialysis patients. Although anti-mycobacterium therapy is highly effective nowadays, the mortality rate is still high because most of the victims have delayed diagnosis. High index of suspiciousness and early diagnosis are mandatory to improve patient outcome. Herein, the authors report a case of TB peritonitis that was suspected because of the disclosure of hypercalcemia and refractoriness to an empirical antibiotic treatment. PMID- 22043584 TI - The "PD First" policy in Thailand: three-years experiences (2008-2011). AB - Universal coverage (UC) scheme is a reformed national healthcare insurance that has been set up since the year 2002 and covers more than 80% of Thai population who are self-employed and do not work as government employees. Initially, this scheme offered only basic and comprehensive healthcare while renal replacement therapy (RRT), the financial cost of which was high, was not included. Without the support from the government healthcare insurance, the patients and their families will become insolvency. The benefit of peritoneal dialysis (PD) over hemodialysis (HD) has been shown in terms of medical expenses and cost effectiveness. The "PD First" policy in Thailand has been implemented on January 1st 2008 as a model of initial treatment of end stage renal disease (ESRD) patients under the UC scheme. During the year 2008-2011, 12,753 cases, 6,177 were male and 6,576 were female, registered in this modality. The technical survivals at 1, 2 and 3 years were 92, 85 and 80%, respectively while the patient survivals were 79, 66 and 57% at 1, 2 and 3 years, respectively. The hematocrit level had been significantly increased from 25.9 +/- 5% in October 2009 to 28.0 +/- 5% in October 2010. The Peritonitis rate was decreased from 20.7 per patient months during the year 2009 to 25.8 per patient months at the year 2011 and the exit site infection rate was 1 episode per 40.7 patient months. Currently, there are 111 PD centers that service for ESRD patients nationwide. There are strong supports from The National Health Security Office, The Nephrology Society of Thailand, The Dialysis Nurse Association, The Kidney Foundation of Thailand The Ministry of Public Health, The Thai Kidney Patient Association, Chulalongkorn University, Thai Red Cross Society, community, and social network, all of which are the major factors to guarantee the salutary outcomes in the future. PMID- 22043585 TI - Nationwide peritoneal dialysis nurse training in Thailand: 3-year experience. AB - Peritoneal dialysis (PD) center is not possible to operate if there is no availability of dedicated PD nurse. Generally, the nurse has to play many roles, including educator coordinator, and sometimes leader. As professionalism, the PD nurses need to have both theoretical and practical skills. With the tremendous leap of PD population after the launch of "PD First" policy in Thailand, the shortage of skillful PD nurse is concerned. Hence, the nationwide PD nurse training course was established with the collaborations of many organizations and institutes. Until now, 3 generations of 225 PD nurses are the productions of the course. This number represents 80 percent of PD nurses distributed throughout the whole nation. The survey operated in the year 2010 demonstrated that the output of the course was acceptable in terms of quality since most of the trained PD nurses had a confidence in taking care of PD patients. The quality of patient care is good as indicated by KPIs. PMID- 22043586 TI - Practical guidelines for automated peritoneal dialysis. AB - The development of APD technologies enables physician to customize PD treatment for optimal dialysis. Dialysis dose can be increased with APD alone or in conjunction with daytime dwells. Although there is no strong evidence of the advantage over CAPD, APD is generally recommended for patients having a high peritoneal transport, outflow problems or high intraperitoneal pressure (IPP) and those who depend on caregivers for their dialysis. The benefits of APD over CAPD depends on the problems and treatment results among dialysis centers. Before starting the APD, medical, psychosocial and financial aspects, catheter function, residual renal function (RRF), body surface area and peritoneal transport characteristic must be evaluated. The recommended starting prescription for APD is the dwell volume of 1,500 ml/m2, 2 hours/cycle, and 5 cycles/session, which will provides 10-15 L of total volume and 10 hours per session. The IPP should be monitored and kept below 18 cmH2O. NIPD is accepted for patients with significant RRF. Anuric patients usually require 15-20 L of total fill volume and may need 1 2 day-dwells of 2L icodextrin or hypertonic glucose solutions. Small solute clearances and ultrafiltration depend on the peritoneal catheter function and dialysis schedule. The clinical outcomes and small solute clearances must be monitored and adjusted accordingly to meet the weekly total Kt/V urea > or = 1.7 and in low peritoneal transporters, the weekly total CCr should be > or = 45 L/1.73 m2. The volume status must be normal. To diagnose the peritonitis in NIPD patients, 1 L of PDF should be infused and permitted to dwell for 2 hours before sending for analysis. The differential of white cell count may be more useful than the total cell counts. In Siriraj Hospital, APD patients had 1.5-3 times less peritonitis than CAPD patients and most of our anuric patients can achieve the weekly total Kt/V urea target with 10 L of NIPD. PMID- 22043587 TI - An update on RAAS blockade and peritoneal membrane preservation: the ace of art. AB - Peritoneal membrane changes over time in long-term peritoneal dialysis (PD) patients lead to dialysis failure and increased morbidity as well as mortality. Bio-incompatable PD solution, peritonitis, and uremia are hypothesized in causing membrane damage. Fibrous organization and angiogenesis of peritoneum are crucial morphological alterations which can diminish the efficacy of exchange and cause ultrafiltration failure. Pathophysiologic mechanisms of membrane damage have been extensively studied to innovate therapeutic strategies. One of the potential mechanisms is a presence of local renin-angiotensin-aldosterone system (RAAS) by which injured peritoneal mesothelial cell-derived angiotensin-II (AII) causes activations in TGF-beta, VEGF expression, and epithelial-to-mesenchymal transition (EMT) which contributes to extracellular matrix accumulation and neoangiogenesis in submesothelial tissues. Clinical evidence of RAAS blockade on human peritoneal membrane remains under investigation and is still inconclusive but relevant data seem to demonstrate its benefit on membrane preservation. Longitudinal effect of RAAS blockade on membrane structural, functional, and clinical relationships and strategies to use angiotensin converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), aldosterone antagonist, and direct renin inhibitor are an interesting field to be explored. PMID- 22043588 TI - Continuous quality improvement process pin-points delays, speeds STEMI patients to life-saving treatment. AB - Using a multidisciplinary team approach, the University of California, San Diego, Health System has been able to significantly reduce average door-to-balloon angioplasty times for patients with the most severe form of heart attacks, beating national recommendations by more than a third. The multidisciplinary team meets monthly to review all cases involving patients with ST-segment-elevation myocardial infarctions (STEMI) to see where process improvements can be made. Using this continuous quality improvement (CQI) process, the health system has reduced average door-to-balloon times from 120 minutes to less than 60 minutes, and administrators are now aiming for further progress. Among the improvements instituted by the multidisciplinary team are the implementation of a "greeter" with enough clinical expertise to quickly pick up on potential STEMI heart attacks as soon as patients walk into the ED, and the purchase of an electrocardiogram (EKG) machine so that evaluations can be done in the triage area. ED staff have prepared "STEMI" packets, including items such as special IV tubing and disposable leads, so that patients headed for the catheterization laboratory are prepared to undergo the procedure soon after arrival. All the clocks and devices used in the ED are synchronized so that analysts can later review how long it took to complete each step of the care process. Points of delay can then be targeted for improvement. PMID- 22043589 TI - Chest pain units help EDs streamline care, boost throughput for low- to moderate risk patients. AB - Hospitals that see a high volume of patients who present to the ED with chest pain are finding that they can expedite care by establishing a chest pain unit to evaluate the low- to moderate-risk patients who have normal initial electrocardiograms (EKG), but no other apparent conditions that can explain their symptoms. The directors of these units say they have trimmed what used to be a two- to three-day hospital stay to a 10- to 18-hour observation period, and patients are able to leave the hospital with a definitive diagnosis. In its first three weeks of operation, the chest pain ER at Shands Critical Care Center at the University of Florida in Gainesville, FL, helped the hospital reduce low- to moderate-risk admissions by two-thirds. Data on 30-day outcomes from the chest pain center at Providence, RI-based Rhode Island Hospital suggest that only three in every 1000 patients treated has had an adverse cardiovascular event following discharge. The director of the chest pain unit at Palmetto Health Richland in Columbia, SC, says screening and evaluation carried out in the unit have enabled providers to pick up cardiac problems in patients who would not have met the criteria for admission to the hospital in the past. PMID- 22043590 TI - ED diversion: multidisciplinary approach engages high utilizers, helps them better navigate the health care system. AB - Working with partners, the St. Charles Health System in Bend, OR, has implemented an ED diversion project that is helping patients who frequent the ED connect with more appropriate settings for their primary care needs. The hospital identifies high ED utilizers using claims data, then a multidisciplinary engagement team establishes care plans for these patients. The most at-risk patients are paired with community health workers to help them better navigate the health care system. The ED diversion project has reduced unnecessary ED utilization by 45% to 70% in cohorts of patients that the hospital has analyzed thus far. The hospital contracts with a non-profit organization to supply and train community health workers. Community health workers follow a structured model that includes more than 80 different pathways to follow, based on patient conditions. PMID- 22043591 TI - [Claude Bernard pioneer of experimental medicine and clinical research]. AB - With the publication of l"Introduction a l'etude de la medecine experimentale (Introduction to the Study of Experimental Medicine) in 1865, Claude Bernard opened up a new concept in experimental methodology. By stressing the essential link between clinical observation, exploration of the "internal medium", and animal studies, he established the founding principles of clinical research. PMID- 22043592 TI - [How to organize medical research?]. AB - The creation of University Hospital Centers (CHU) in 1958 paved the way for the modern era of medical research in France. A large number of initiatives have subsequently been implemented, one on top of the other, without proper integration within the existing infrastructure. This has resulted in an excessively complex organization of work undertaken in hospitals, universities and research agencies. Other countries have adopted different organizational models. A recent initiative in France is seeking to create a limited number of so called University Hospital Institutes (IHU), within a more flexible system that should favor the development of research projects from the laboratory through to clinical applications. Nevertheless, IHUs will not integrate the different partners' specific missions of each parteners. In the Netherlands, University Medical Centers have been created within a single organization. Ten years later this set-up has proved to be highly successful and could serve as a model for future restructuring of French University Hospital Centers. PMID- 22043593 TI - [ECRIN (European clinical research infrastructures network), a pan-European infrastructure for clinical research]. AB - Clinical research plays a key role both in the development of innovative health products and in the optimisation of medical strategies, leading to evidence-based practice and healthcare cost containment. ECRIN is a distributed ESFRI-roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients, and unlocking latent scientific providing services to multinational. Servicing of multinational trials started during the preparatory phase, and ECRIN has applied for ERIC status in 2011. In parallel, ECRIN has also proposed an FP7 integrating activity project to further develop, upgrade and expand the ECRIN infrastructure built up during the past FP6 and FP7 projects, facilitating an efficient organization of clinical research in Europe, with ECRIN developing generic tools and providing generic services for multinational studies, and supporting the construction of pan-European disease oriented networks that will in turn act as ECRIN users. This organization will improve Europe's attractiveness for industry trials, boost its scientific competitiveness, and result in better healthcare for European citizens. The three medical areas supported in this project (rare diseases, medical devices, and nutrition) will serve as pilots for other biomedical research fields. By creating a single area for clinical research in Europe, this structure will contribute to the implementation of the Europe flagship initiative 2020 'Innovation Union', whose objectives include defragmentation of research and educational capacities, tackling the major societal challenges (starting with healthy aging), and removing barriers to bringing ideas to the market. PMID- 22043594 TI - [Diagnosis of bipolar disorder and rationale of early treatment]. AB - The earlier bipolarity is diagnosed and treated, the better the chances of durable recovery The bipolar spectrum consists of a large panel of clinical syndromes with heterogeneous symptoms. Clinical studies show that, on average, a period of nine years elapses between onset of the first mood symptoms and appropriate prescription of mood stabilizers. Tools such as the bipolarity index can help with earlier and more precise diagnosis of bipolarity, and with the choice of the best treatment to prevent complications of bipolar illness. PMID- 22043595 TI - [Universal implementation of pathogen inactivation in labile blood products is a major step towards transfusion safety]. AB - Transfusion of labile blood products (red cell concentrates, platelet concentrates and plasma) is vital in the absence of alternatives. Patients and doctors have always feared infections transmitted by blood, blood components and blood-derived drugs. It is potentially dangerous to delay implementation of pathogen inactivation in labile blood products pending a perfect process. Universal implementation of pathogen inactivation in labile blood products is a major step towards transfusion safety. PMID- 22043596 TI - Agathos Daimon and the Asklepian serpent. AB - Much conjecture abounds about the origin of the Asklepian serpent of healing, this latter the universal metonym for curative medicine. Iconographic evidence of Asklepios with his staff-entwined serpent exists from Hippocratic times. Many theories exist about the origin of this reptilian symbol of curative medicine. Speculation has ranged from the skin-shed serpent emergent in new and robust health to putative associations with earlier Egyptian and Babylonian anguine (snake) symbols of life-determining power. Other scholars have drawn attention to the Palaeolithic, Neolithic and later Bronze-Age associations with serpent veneration in the context of rain and fertility religious invocations in India; and in many other cultures. In the South Pacific, in Australia and in Central and South America, serpents were regarded as spirits of the earth, often chthonian spirits who possessed life-giving powers. In Chaldean and Arabic etymology, the words for "serpent" and "life" have a synergy. In Classical Greece, the Agathos Daimon was literally the "noble spirit", a personal companion spirit ensuing health and good fortune. The Agathos Daimon was portrayed in iconography as a serpent, or as a fit and comely youth. This paper conjectures that the serpentine Agathos Daimon was one origin of the Asklepian symbol of medicine, portrayed as the serpent associated of the Homeric Asklepios. In later Roman times, the Agathos Daimon was transliterated to the agathodaemon, a protective companion spirit both of individuals and of the homes in which they lived. This benign resident spirit featured prominently in Roman art and was a common feature as a protective household spirit in first century homes at both Pompeii and Herculaneum. The agathodaemon motif also featured on Roman coins, such as bronze diobols of Antoninus Plus (138 - 161 A.D.) from Alexandrian mints in Egypt. In the twenty-first century, the serpentine Agathos Daimon is honoured not only as the symbol of medicine; but is daily acknowledged in toasts to "Good Health". PMID- 22043597 TI - The great Russion surgeon Nikolay Ivanovich Pirogov (1810-1881). AB - In 2010 we celebrated a great date in the world history of medicine--the bicentenary of Nikolay Ivanovich Pirogov, the greatest Russian surgeon and one of the greatest military surgeons of all times, the founder of Surgical (or Topographical) Anatomy and experimental branch of Surgery, a co-founder of Military-field surgery, an educator and a social figure, a man of daring humanistic ideals. Each aspect of his fruitful activities is by itself a subject of special scientific investigation and deep studies. PMID- 22043598 TI - [An encounter between medicine and astronomy: migraine visions]. AB - Until the second half of the eighteenth century, the very definition of migraine as hemicrania (pain felt in one side of the head) eclipsed symptoms that were then considered as "marginal", although tingling sensations, speech impairment and visual impairment had already been described by Piso and Wepfer. The possibility of a migraine without a headache nevertheless started to be envisaged, inviting one to re-evaluate the status of these phenomena. But, as paradoxical as it may seem, it is in the field of astronomy that some of these phenomena such as visual aberrations were analyzed systematically and acknowledged to be migrainous. Scintillating scotoma is no exception: it was indeed mentioned as early as in the Hippocratic corpus, but until the end of the nineteenth century it was addressed as a separate condition to migraine. We limit our study to the visual aura. Our purpose is to show that the ophthalmic symptoms affecting migraine sufferers were not, by themselves, a medical object--which somehow calls into question the very functioning of science. PMID- 22043599 TI - The last months of Andreas Vesalius: Part II--From Jerusalem to Zakynthos (Zante). AB - Returning from his pilgrimage to the Holy Land Vesalius encountered serious trouble, as a consequence of which he died on the Greek island Zakynthos. Following a discussion of the circumstances of his death and what is known about his grave, we examine also Vesalius's intentions for the period after his journey. PMID- 22043600 TI - Heart failure in Penzance--a cornish enigma. AB - Following his discharge from the Royal Navy at the end of the Napoleonic Wars in 1816, Dr John Forbes (1787-1861) studied at the University of Edinburgh and gained his MD degree in the following year. He moved to Cornwall in September 1817 and started using a primitive stethoscope. In 1821 he translated Laennec's classical De L'Auscultation Mediate (1819) into English.As physician to Penzance Public Dispensary, his clinical experience in the local population is meticulously recorded in a large series of case notes of patients seen by him between 10 April and 4 December 1821. The casebooks are now in the care of Aberdeen University Library. PMID- 22043601 TI - Epidemic waves during Justinian's plague in the Byzantine Empire (6th-8th c. AD). AB - The aim of the present study is to collect the epidemic outbreaks and the epidemic waves of the bubonic plague of the Byzantine Empire during the first pandemic (541-751 AD). Human activities, such as trade and military movements have been speculated as underlying factors for the causation of the pandemic. Historical data combined with geographical spreading of the plague, allows an alternative speculation of suspicious enzootic areas in the Middle East. We conclude that the possible existence of enzootic areas in that region might have been responsible for the causation of the numerous outbreaks of the bubonic plague in the Eastern provinces of the Byzantine Empire during the 6th-8th century period. PMID- 22043602 TI - Human tumor stem cells, the petri dish and the patient. A tribute to Sydney E. Salmon. AB - During the last ten years, much work has been devoted to the concept of tumor stem cells, a concept first introduced by Virchow in 1855. Despite the importance and the quality of these works, they ignore the major step forward made by SE Salmon and his group from the University ofArizona atTucson, USA, during the seventies'. The purpose of this review is to (i) contribute to the original work of SE Salmon as a pioneer in the field of cancer stem cell research (ii) emphasize the importance of his contribution in this field of research and (iii) underline the other fields of his research, especially in the domain of mathematical oncology. Finally, we would like to show that SE Salmon made Multiple Myeloma a model in Oncology, many study groups being engaged into Myeloma research now in the world. PMID- 22043603 TI - Historical sources about diseases, death and embalming regarding the family of Jean Antoine Michel Agar, Minister of Finance of Gioacchino Murat. AB - Among the mummies preserved in the Basilica of San Domenico Maggiore in Naples, there are the bodies of the wife and three children of Jean Antoine Michel Agar, Minister of Finance of Naple's Kingdom during the Monarchy of Joachim Murat (1808 1815). Between 1983 and 1987 paleopathological analyses were performed; in particular, X-ray examination allowed investigation of the health status of the Agar family members and reconstruction of the embalming processes used to preserve the bodies. In addition, an analysis of the historical and archival documents was carried out, to formulate hypotheses about the causes of death, demonstrating how these sources could become important instruments to obtain diagnoses and pathological histories. PMID- 22043604 TI - [Smallpox at the Hotel Dieu of Paris in 1900. An unpublished letter of Professor Brissaud]. AB - On November 26, 1900, Rene Monod, resident in Professor E douard Brissaud's department, wrote at Brissaud's request a report on the cases of smallpox which had happened in his department at the Hotel-Dieu since September. This unpublished document attests to Brissaud's interest in hygienism, Pasteurism and Jennerian vaccination. PMID- 22043605 TI - The essential CEO appraisal. PMID- 22043606 TI - Planning under pressure. AB - Delivery system transformation brings a new urgency to the strategic planning process. Trustees will need to make quicker decisions and embrace far shorter timelines. PMID- 22043607 TI - The bundled payment battle. AB - As hospitals bundle services, administrators will have to take a close look at clinical costs. Resolving conflicts with physicians will require strong leadership. PMID- 22043608 TI - 2012 AHA environmental scan. PMID- 22043609 TI - Dangerous board diseases. AB - Unproductive meetings? Ill-informed decisions? Ineffective leadership? These and other symptoms point to common governance diseases. Learn how to prevent and cure them. PMID- 22043610 TI - ED throughput. PMID- 22043611 TI - Compensatory justice. PMID- 22043612 TI - Beyond the brainstorm. AB - The secret to innovation? Three Cs: competency, culture and courage. PMID- 22043613 TI - Physician-hospital arrangements. PMID- 22043614 TI - [How the care of COPD will be better]. PMID- 22043615 TI - [A "failed" pelvic reservoir doesn't require extirpation. It can instead be converted to Kock's pouch--a good therapeutic alternative]. PMID- 22043616 TI - [Big differences in Swedish child health care. Child health care units decide their services--alarming that a national program is missing]. PMID- 22043617 TI - [Spontaneous intracranial hypotension probably underdiagnosed. Newly occurring orthostatic headache a warning of the condition]. PMID- 22043618 TI - [Psychosocial intervention in schizophrenia or schizophrenia-like conditions. A life as normal as possible--the target in new national guidelines]. PMID- 22043619 TI - [Assessment of dangerousness of narcotics requires better expert evidence service]. PMID- 22043620 TI - [Important to discuss breast feeding]. PMID- 22043621 TI - [Boxing: traumatology and prevention]. AB - In 1986, a surgeon who, as an amateur boxer himself was concerned with boxers' health, approached a pioneering Parisian neuroimaging unit. Thus began a study in close cooperation with the French Boxing Federation, spanning 25 years. In a first series of 52 volunteer boxers (13 amateurs and 39 professionals), during which MRI gradually replaced computed tomography, ten risk factors were identified, which notably included boxing style: only one of 40 "stylists" with a good boxing technique had cortical atrophy (4.5 %), compared to 15 % of "sloggers". Changes to the French Boxing Federation rules placed the accent on medical prevention. The second series, of 247 boxers (81 amateurs and 266 professionals), showed a clear improvement, as lesions were suspected in 14 individuals, of which only 4 (1.35 %) were probably due to boxing. The third and fourth series were part of a protocol called "Brain-Boxing-Ageing", which included 76 boxers (11 having suffered KOs) and 120 MRI scans, with reproducible CT and MRI acquisitions (9 sequences with 1.5 T then 3 T, and CT). MRI anomalies secondary to boxing were found in 11 % of amateurs and 38 % of professionals (atrophy, high vascular T2 signal areas, 2 cases of post-KO subdural bleeding). CT revealed sinus damage in 13 % of the amateurs and 19 % of the professionals. The risk of acute and chronic facial and brain damage was underline, along with detailed precautionary measures (organization of bouts, role of the referee and ringside doctor, and application of French Boxing Federation rules). PMID- 22043622 TI - [Sport-related sudden death and its prevention]. AB - Sudden death of sportspersons is frequently in the news but is relatively uncommon when the total number of sudden deaths is taken into account (1500 vs 40 000 per year in France for example). Sport-related sudden death is often due to an unrecognized or underestimated cardiovascular disorder. The immediate causes of this dramatic event are age-dependent. Before 35, the most frequent causes are hypertrophic cardiomyopathy and arythmogenic right ventricular cardiomyopathy, while complications of coronary atheroma predominate later. Prevention begins with screening, which remains imperfect. Patients with cardiovascular disorders at risk of sudden death must adapt their sports activities accordingly. Knowledge of life-saving first-aid procedures by those supervising sports activities can improve the prognosis. PMID- 22043623 TI - [Sports injuries and their prevention in childhood and adolescence]. AB - Sports injuries are common in children and adolescents. Typical musculoskeletal disorders include overuse injuries such as stress fractures and apophyseal avulsions. Gymnastics has one of the highest injury rates of all girls' sports. Intensive gymnastics can cause chronic spine and wrist trauma. Prevention of sport injuries should be a priority for parents, coaches and children themselves. Protection (helmet, padding) is mandatory for some activities. Proper education and preparation are necessary for all sports activities. PMID- 22043624 TI - [Stimulation therapies for Parkinson's disease: over the past two decades]. AB - Levodopa has been the mainstay of treatment for Parkinson's disease since the 1960s, but the dyskinesias it induces are a major drawback. High-frequency deep brain stimulation offers a safe, reversible alternative. Targets include the thalamus, pallidum, subthalamic nucleus and, more recently, the pedunculopntine nucleus, which requires low-frequency excitation. The subthalamic nucleus is the preferred target in Parkinson's disease. Other treatments such as gene therapy are in the pipeline. PMID- 22043625 TI - [Update on the pathophysiology of Parkinson' disease]. AB - Changes in the substantia nigra of patients with Parkinson's disease were suspected by Brissaud in the late 19th century. They were subsequently confirmed by Tretiakoff but neglected by Lewy, who described the inclusion bodies that bear his name. The experimental Parkinsonian syndrome caused by reserpine led Carlsson to discover the neuromediatory role of dopamine, a finding at the origin of L DOPA therapy. Identification of a mutation of the alpha-synuclein gene in cases of familial Parkinson's disease with autosomal dominant transmission was followed by the detection of the protein product in Lewy bodies and neurites. Alpha synuclein is now recognized as being the main constituent of Lewy bodies. Alpha synuclein immunohistochemistry has revealed that lesions can extend from the autonomous nervous system to the cortex (in Lewy body dementia). The Lewy body itself does not appear to be the direct cause of symptoms, which correlate better with neuronal death. Neuronal death could be due to metabolic disturbances related to alpha-synuclein accumulation, ubiquitin-proteasome system dysfunction, or oxidative stress. Non-autonomous cell death, caused by neuro-inflammation or gliosis, has also been incriminated. PMID- 22043626 TI - [Psychological and behavioural disorders in Parkinson's disease]. AB - Psychological and behavioral disorders associated with Parkinson's disease can have a major impact on patients' and caregivers' quality of life. Depression, anxiety, psychotic symptoms (e.g hallucinations), apathy and impulse-control disorders raise questions as to the respective roles of premorbid vulnerability, disease-related factors, and drug adverse effects. These disorders are often difficult to manage, and there is an unmet need for controlled trials in this field. PMID- 22043627 TI - [Pathophysiology of Parkinson's disease: an update]. AB - Considerable progress has been made in the pathophysiology of Parkinson's disease in the last 25 years. To better understand the nature and diversity of the symptoms of Parkinson's disease it is necessary to integrate clinical knowledge on 1) the role of dopamine, 2) the anatomical and functional organization of the basal ganglia, and 3) the dysfunctions observed in MPTP-treated monkeys. This article reviews the principal discoveries in these three research fields and their contribution to our understanding of the pathophysiology of Parkinson's disease. PMID- 22043628 TI - [Tracheal allotransplantation after withdrawal of immunosuppressive therapy]. AB - Reconstruction of long-segment tracheal defects requires a vascularized allograft. We report successful tracheal allotransplantation after indirect revascularization of the graft in a heterotopic position. Immunosuppressive therapy was administered before the operation, and the tracheal allograft was wrapped in the recipient's forearm fascia. Once revascularization was achieved, the mucosal lining was replaced progressively with buccal mucosa from the recipient. At 4 months, the tracheal chimera was fully lined with mucosa, which consisted of respiratory epithelium from the donor and buccal mucosa from the recipient. After withdrawal of immunosuppressive therapy, the tracheal allograft was moved to its correct anatomical position with an intact blood supply. No treatment-limiting adverse effects occurred. PMID- 22043629 TI - [Skin engineering for burns treatment]. AB - Severely burned patients need effective and permanent wound coverage. The outcome of massive burn injuries has improved with the use of cultured epithelial autografts (CEA), despite their fragility, frequent failure to take, high cost and long-term tendency to contract. Combining CEA with dermal substitutes provides earlier skin closure and satisfactory functional results. Another promising line of research is skin regeneration with epidermal stem cells, which have the capacity to differentiate into keratinocytes, to promote wound repair, and to regenerate skin appendages. Human mesenchymal stem cells have been evaluated in radiation-induced skin damage. PMID- 22043630 TI - [Canine atopic dermatitis]. AB - Canine atopic dermatitis is an inflammatory skin disease characterized by typical clinical signs and affecting up to 10 % of dogs aged from 1 to 3 years. The diagnosis is mainly clinical and the treatment is complex. This canine form may offer a good model of human atopic dermatitis, as the two diseases show many pathogenetic, clinical and therapeutic similarities. PMID- 22043631 TI - [Epitheliotropic lymphomas: better identification for improved treatment]. AB - Mycosis fungoides is the most frequent cutaneous T cell lymphoma. Mycosis fungoides-related cutaneous T cell lymphomas include folliculotropic mycosis fungoides, with or without mucinosis, pagetoid reticulosis and granulomatous slack skin. Sezary syndrome is characterized by pruriginous erythroderma, adenopathies, atypical lymphocytes in the blood and a more aggressive course. B cell lymphomas represent 25 % of cutaneous lymphomas. Primary cutaneous follicle center cell lymphomas are the most frequent. They are often located on the head and trunk and have an indolent course. Primary cutaneous marginal zone B-cell lymphomas, which are more frequently multicentric and located on the limbs, also have an indolent course. In contrast, primary cutaneous diffuse large B-cell lymphomas, leg type, and primary cutaneous intravascular large B-cell lymphomas have a more aggressive course. Treatment must be adapted to each case. Unnecessarily aggressive treatments must be avoided in patients with indolent lymphomas. PMID- 22043632 TI - [Immunotherapy of melanoma]. AB - This article describes current concepts and future challenges in non specific immunotherapy, vaccination, and antigen-specific adoptive immunotherapy of melanoma. If these treatments are to realize their full potential, it will be essential to understand how the tumor induces immune tolerance. PMID- 22043633 TI - [Responsibility for technical dental work]. PMID- 22043634 TI - [Making extra money]. PMID- 22043635 TI - [Dentist can detect diseases early. Yes]. PMID- 22043636 TI - [Dentist can detect diseases early. No]. PMID- 22043637 TI - [Hans Selye, the father of stress]. PMID- 22043638 TI - [Problems with the availability of drugs in The Netherlands]. AB - The withdrawal ofa license to trade can result in problems with the availability of drugs. The reasons for withdrawal can be ofan economic nature, but the balance between effectiveness and side effects of a drug can also, after a period of time, prove disappointing and the drug can, as a result, be withdrawn from sale. A scarcity of basic materials, too, can play a role in availability, as can the inability of the manufacturer to meet the standards of the relevant authority. PMID- 22043639 TI - [Severe odontalgic pain preceding migraine attacks]. AB - A 30-year-old woman appeared at the gnathology department of a centre for special dentistry complaining of migraine attacks which were preceded each time by severe odontalgic pain. Furthermore, she suffered from an autoimmune disease as well as from tension headaches. The oral health care provider in charge suspected that the episodes of odontalgic pain, which lasted for several hours or even several days, were caused by bruxism. Treatment of the bruxism resulted in reduced pain as well as reduced severity of the migraine attacks. PMID- 22043640 TI - [Cosmetic facial surgery. The application of botulinum neurotoxin type A]. AB - During the past decade, cosmetic facial treatments have become a standard element of the work of both dentists and oral and maxillofacial surgeons. A shift has taken place from invasive surgical treatments in the direction of minimally invasive treatments. One of the most frequently carried out minimally invasive treatments is the treatment with botulinum neurotoxin type A. Since botulism was first described in the 18th century, this neurotoxin has undergone a slow development to botox which is now manufactured. Botox attaches itself to the nerve endings and is subsequently taken up in the vesicles which contain acetylcholine. Botox blocks, there, the protein which is responsible for the production of acetylcholine. Botox reduces wrinkles in the skin at the muscles offacial expression and is therefore employed in areas with dynamic wrinkles. Appropriate areas include frown lines in the glabella, lines in the forehead, lateral periorbital lines, hyperactivity in the muscles of the upper lip, hypertrophy of the musculus masseter. PMID- 22043641 TI - [Dissertations 25 years after date 29. CO2 laser surgery of leukoplakia of the oral mucosa]. AB - With a CO2 laser superficial lesions of the oral mucosa can be removed by evaporation. During CO2 laser evaporation there is minimal damage to the surrounding tissue, resulting in minimal scarring after healing. Therefore the CO2 laser seems to be a modality which is appropriate for the treatment of leukoplakia of the oral mucosa. In 1985, the effect of CO2 laser light on mucosa and the healing after CO2 laser evaporation was studied. In addition, clinical research was carried out concerning the effectiveness of CO2 laser evaporation in the treatment of 103 cases of leukoplakia of the oral mucosa The cure-rate was 91% and no malignant degenerations were seen in the treated area. The group was expanded (282) and evaluated again, with a cure-rate of 90%. In 1% of the cases, malignant degenerations were seen. CO2 laser evaporation seems the modality of choice for the treatment of leukoplakia of the oral mucosa. PMID- 22043642 TI - [Dissertations 25 years after date 30. Oral hygiene and dental hygienists]. AB - In 1986 the thesis entitled 'Choosing for dental hygienists' was published in The Netherlands. It provided the scientific basis for the further development of the profession of dental hygienists in The Netherlands. Since then, the profession has developed very strongly. In the intervening years, qualified dental hygienists have come to be considered capable of taking over simple restorative treatments from dentists. As a result, treatment, especially in children, can largely be carried out by one person. Nevertheless, recent developments, such as the sharp increase in the number of new dental students, suggest that the re allocation of responsibilities is proceeding slowly. This suggests that policy makers have not yet unambiguously opted for dental hygienists and prevention. PMID- 22043643 TI - Nursing home quality, staffing, and malpractice paid-losses. AB - Litigation activity against Florida's nursing home providers increased dramatically over the past two decades. This has been a significant concern for policy makers and nursing home administrators as they attempt to balance the realities of negligent behavior with its impact on the overall cost and quality of long-term care. This study uses Medicare Cost Report data and OSCAR (Online Survey, Certification, and Reporting) data for Florida's nursing facilities over a five-year period from 2001 to 2005 to examine the effect of quality and staffing on malpractice paid-losses. The results from the multiple regression analyses indicate that staffing levels are strongly associated with paid-losses for malpractice claims. Nursing homes with higher registered nurse to resident ratios are less likely to experience malpractice paid-losses. In contrast, higher nursing assistant to resident ratios are significantly related to higher probability of malpractice paid-losses. The effect of total deficiency on malpractice is not significant. These findings suggest that increases in more skilled nurse staffing are associated with lower likelihood of nursing home malpractice paid-losses. However, nursing homes need to balance the overall cost and quality of their facilities related to staffing and malpractice litigations. PMID- 22043644 TI - The effect of health payment reforms on cost containment in Taiwan hospitals: the agency theory perspective. AB - This study aims to determine whether the Taiwanese government's implementation of new health care payment reforms (the National Health Insurance with fee-for service (NHI-FFS) and global budget (NHI-GB)) has resulted in better cost containment. Also, the question arises under the agency theory whether the monitoring system is effective in reducing the risk of information asymmetry. This study uses panel data analysis with fixed effects model to investigate changes in cost containment at Taipei municipal hospitals before and after adopting reforms from 1989 to 2004. The results show that the monitoring system does not reduce information asymmetry to improve cost containment under the NHI FFS. In addition, after adopting the NHI-GB system, health care costs are controlled based on an improved monitoring system in the policymaker's point of view. This may suggest that the NHI's fee-for-services system actually causes health care resource waste. The GB may solve the problems of controlling health care costs only on the macro side. PMID- 22043645 TI - Financing development stage biotechnology companies: RMs vs. IPOs. AB - We examine reverse mergers (RMs) in the biotechnology industry and find that, when compared to initial public offerings (IPOs), RMs are smaller, have significantly lower market valuations relative to size, and generally invest less. We also find that RMs exhibit positive abnormal returns on the announcement date and throughout the first year after the RM event. In looking at liquidity measures, we find that RMs tend to be less liquid than IPOs and that illiquidity is greater during the six-month lock-up period following the RM event. Thus, RMs may be an appropriate alternative financing vehicle in capital intensive, high risk biotechnology companies which require accessing deeper and larger pools of investors in public capital markets across multiple milestone periods in a "pay for progress" environment. PMID- 22043646 TI - The impact of competition among health care financing authorities on market yields and issuer interest expenses. AB - The main source of capital for non-for-profit health care organizations is tax exempt municipal bonds. The tax-exempt nature of this debt requires that they be issued through financing authorities, which are run by, or affiliated with, state or local government agencies. In some states, all tax-exempt health care bonds must be issued through a single financing authority, but in other states the issuing health care organization has a choice of multiple authorities. Using a Herfindahl index of issuer concentration, prior research has found that greater competition among authorities results in lower interest costs to the issuing health care organization. We pick up where this earlier study left off, examining the links between authority competition, the interest expenses to the issuer, and the yield to the market investor. Although our analysis of all hospital bonds issued between 1994 and 2002 corroborates earlier findings with regard to interest expenses to the issuing health care organization, we also find market yield is lower for statewide authorities where issuer concentration is lower. Thus, authority competition is good from the issuers' point of view, but holds no favor in the investors' eyes. On the other hand, the lower market yield associated with statewide authorities does not make its way down to the issuer in the form of lower interest costs. To help sort through this paradox, we explore our findings through interviews of executives in state issuing authorities. PMID- 22043647 TI - Hospital specialization: product-line planning during the market reformation. AB - Rational expectations theory dictates that firms respond to shifts in the demand function as a result of substantial reforms in the insurance marketplace. Federal health reform has enhanced the benefits of specialization. Hospital product-line specialization trends are studied using multiple regression analysis for the period 2001-2010. The observed 32.8 percent rise in specialization was associated with a 9.8 percent decline in unit cost per admission. The number of specialized hospitals has grown by 174 percent in the past decade. Other hospitals are getting more specialized by reducing their product lines. Specialization has been highest in competitive West Coast markets and lowest in the rate-regulated states (New York and Massachusetts). Hospitals have less incentive to contain costs by decreasing the array of services offered in stringent rate-setting states. The term "underspecialization" is advanced to capture the inability of some hospitals to selectively prune out product lines in order to specialize. Such hospitals spread resources so thinly that many good departments suffer. Unit cost per case (DRG-adjusted) is higher in the less specialized hospitals. PMID- 22043648 TI - Summary of prospective quantification of reimbursement recovery from inpatient acute care outliers. AB - The purpose of this study is to identify and quantify inpatient acute care hospital cases that are eligible for additional financial reimbursement. Acute care hospitals are reimbursed by third-party payers on behalf of their patients. Reimbursement is a fixed amount dependent primarily upon the diagnostic related group (DRG) of the case and the service intensity weight of the individual hospital. This method is used by nearly all third-party payers. For a given case, reimbursement is fixed (all else being equal) until a certain threshold level of charges, the cost outlier threshold, is reached. Above this amount the hospital is partially reimbursed for additional charges above the cost outlier threshold. Hospital discharge information has been described as having an error rate of between 7 and 22 percent in attribution of basic case characteristics. It can be expected that there is a significant error rate in the attribution of charges as well. This could be due to miscategorization of the case, misapplication of charges, or other causes. Identification of likely cases eligible for additional reimbursement would alleviate financial pressure where hospitals would have to absorb high expenses for outlier cases. Determining predicted values for total charges for each case was accomplished by exploring associative relationships between charges and case-specific variables. These variables were clinical, demographic, and administrative. Year-by-year comparisons show that these relationships appear stable throughout the five-year period under study. Beta coefficients developed in Year 1 are applied to develop predictions for Year 3 cases. This was also done for year pairs 2 and 4, and 3 and 5. Based on the predicted and actual value of charges, recovery amounts were calculated for each case in the second year of the year pairs. The year gap is necessary to allow for collection and analysis of the data of the first year of each pair. The analysis was performed in two parts. First, cases of myocardial infarction were examined to prove feasibility and then a sample of strata of all cases were subjected to the same analytical procedure to provide support for the postulation of universal applicability. Approximately 85,000 cases could be audited annually in New York State, and possibly 1.3 million in the entire United States. Estimated recovery from all inpatient cases is approximately $230 million per year in New York State and roughly $3.6 billion per year from these payers on a national basis. The cost benefits ratio was estimated at 3.6:1. These are considered to be conservative estimates. PMID- 22043649 TI - Radio frequency identification: the big role player in health care management. AB - PURPOSE: This paper seeks to review the fundamental concepts of radio frequency identification (RFID) and to discuss the fact that the road to success for healthcare systems is the thorough management of patients, employees, equipment, medications, and records throughout the industry. Thereafter, it aims to prepare a deep review of the technology, study seven new cases on the topic of healthcare management and deliver a broad applications area thereof. DESIGN/METHODOLOGY/APPROACH: The paper identifies key elements of RFID through the review of healthcare management literature and case studies. For this purpose, seven cases from the healthcare industry are reviewed to demonstrate the extent of the applications of RFID in this area. FINDINGS: To make healthcare management systems functional and successfully operational, RFID solutions can be used to reduce operating costs through management of patients, employees, equipment, medications, and records to improve tracking and tracing, and preventing the lost of resources under any circumstances. ORIGINALITY/VALUE: This paper delivers a review of RFID on the healthcare industry. For this reason, the basic and key point on RFID technology is discussed and seven cases from the literature are reviewed. PMID- 22043650 TI - The mediating role of organizational subcultures in health care organizations. AB - PURPOSE: This study aims to investigate the mediating role of organizational subculture between job satisfaction, organizational commitment (dependent variables) and leadership, culture (independent variables) in health care organizations. DESIGN/METHODOLOGY/APPROACH: A survey on nurses from 26 wards from various types of hospital was used. A total of 251 usable returns were collected for the analysis (i.e. response rate of 63 per cent). Structural equation analysis was conducted to obtain the best fit model and to determine the direction of the causal effect between job satisfaction and commitment, and the role of subculture as a mediating variable, between commitment of its other antecedents. FINDINGS: Comparisons with alternative models confirmed satisfaction as an antecedent of commitment and the role of subculture as a mediating variable. The results of this study contribute to the clarification of the causal relations of the antecedents of commitment, and highlight the important role of local leadership and subculture in determining employees' job satisfaction and commitment. RESEARCH LIMITATIONS/IMPLICATIONS: The results of this study should not be generalized to other industries and other national cultural context. Furthermore, a longitudinal study may be necessary to determine the causal relationship of variables used in this study. PRACTICAL IMPLICATIONS: The findings could provide managers with valuable insight to focus their limited resources on improving the level of organizational commitment via the mediating role of organizational culture. ORIGINALITY/VALUE: The research findings provide managers with a new lens to examine organizational culture using the three perspectives of: bureaucratic, supportive, and innovative. Furthermore, the results could renew interest in developing other organizational subculture models that determine the relationship between organizational subculture and commitment PMID- 22043651 TI - Organizational culture based on the example of an Estonian hospital. AB - PURPOSE: The concept of organisational culture (also referred to later as OC) is one of the approaches in modern organisational analysis exploring the values, attitudes and beliefs behind human behaviour in the workplace. OC as a social phenomenon is considered to be important for the sustainability of every organisation. In the service sector, OC may affect the nature and quality of the services provided. The aim of this paper is twofold: on the one hand, to highlight the patterns of OC in a hospital; and, on the other hand, to outline relationships between OC and patient satisfaction. The study was conducted in Tartu University Hospital, one of the most influential health care organisations in Estonia. This paper has original value by presenting an insight into organisational culture in the Estonian health care sector, and the findings of the study will expand knowledge of OC in the health care sector in general. DESIGN/METHODOLOGY/APPROACH: The OC instrument applied in a quantitative cross sectional study was earlier developed according to the Competing Values Framework (CVF). Data from 456 medical and non-medical professionals were analysed using non-parametric tests of descriptive statistics. A factor analysis was performed to assess the instrument's compatibility for analysing the OC pattern in the health care sector. FINDINGS: The dominant culture type in all the groups investigated was the Internal Processes type, mainly followed by the Rational Goal type, while different cultural patterns were observed in professional groups. The factor analysis yielded a three-subscale solution. Clinics with high patient satisfaction did not score more than clinics with low patient satisfaction in terms of the Human Relations type. ORIGINALITY/VALUE: In future studies a random sample design and a multidisciplinary approach to OC research should be followed in order to further explore OC patterns in hospitals and their consequences for different aspects of hospital performance. PMID- 22043652 TI - Health care policies and resisting consumers in a prototypical welfare state. AB - PURPOSE: It has been argued by researchers from the Anglo-Saxon nations that the rationality of the market has increasingly infiltrated the medical field. This paper seeks to enquire via policy analysis to what extent these principles have affected the prototypical welfare state of Denmark in relation to Danish hearing health policies. DESIGN/METHODOLOGY/APPROACH: The paper is based on qualitative methods comprising observations and interviews in two hearing clinics. FINDINGS: The paper shows that rather than a "withdrawal" of the state there has been a process of reform. The data suggest that a distinguishing mark of the consumer role on offer in Denmark is that, along with a free hearing aid, the Danish health consumer enjoys a range of rights and reciprocal responsibilities. The paper concludes that few of the hearing-impaired patients were able to embrace the consumer ethos, and those who chose not to wear their prescribed hearing aids experienced the added burden of moral reproach. ORIGINALITY/VALUE: It makes little sense to analyse abstracted rationalities without proceeding to analyse how they actually function in practice. This paper demonstrates empirically how and to what degree governmentality is embedded in social practice in two public hearing clinics in Denmark. PMID- 22043653 TI - The trade-off between efficiency and quality in hospital departments. AB - PURPOSE: Hospital managers are confronted with decisions that have to account for multiple objectives, which may be in conflict with regard to efficiency and quality of care. In empirical studies occupancy and staffing ratios as well as in hospital mortality are frequently used measures for efficiency and quality-of care, respectively. Efficiency and quality measures vary on a daily basis. However, most empirical studies fail to take this variation into account, especially because data of daily staffing levels are lacking. The paper seeks to exploit the notion that staffing levels are planned according to expected occupancy levels, i.e. estimated daily occupancy levels account for unobserved daily staffing levels. DESIGN/METHODOLOGY/APPROACH: Using administrative data from 2004 for a sample of 62 departments in 33 German hospitals, the relation between daily occupancy levels and in-hospital mortality count on the department level is analyzed. In an OLS-framework the paper estimates daily occupancy level for all departments and then uses the predicted occupancy levels in a zero inflated Poisson (ZIP) regression framework to explain in-hospital mortality count. FINDINGS: The results show a potential trade-off relation between predicted occupancy rates and mortality. More specifically, the paper finds that the trade-off relation is less pronounced in hospitals with a higher number of available staff per bed. ORIGINALITY/VALUE: First, the paper shows evidence for a negative trade-off between measures of managerial and medical performance on a day-to-day basis. Second, interactions between single measures of efficiency are modeled, namely predicted occupancy rate and staff per bed ratios, and policy implications are developed. Third, first empirical results in this respect using German data are presented. PMID- 22043654 TI - Regulating time commitments in healthcare organizations: managers' boundary approaches at work and in life. AB - PURPOSE: The purpose of this paper is to explore managers' boundary setting in order to better understand their handling of time commitment to work activities, stress, and recovery during everyday work and at home. DESIGN/METHODOLOGY/APPROACH: The paper has qualitatively-driven, mixed method design including observational data, individual interviews, and focus group discussions. Data were analyzed according to Charmaz' view on constructivist grounded theory. FINDINGS: A first step in boundary setting was to recognize areas with conflicting expectations and inexhaustible needs. Second, strategies were formed through negotiating the handling of managerial time commitment, resulting in boundary-setting, but also boundary-dissolving, approaches. The continuous process of individual recognition and negotiation could work as a form of proactive coping, provided that it was acknowledged and questioned. RESEARCH LIMITATIONS/IMPLICATIONS: These findings suggest that recognition of perceived boundary challenges can affect stress and coping. It would therefore be interesting to more accurately assess stress, coping, and health status among managers by means of other methodologies (e.g. physiological assessments). PRACTICAL IMPLICATIONS: In regulating managers' work assignments, work-related stress and recovery, it seems important to: acknowledge boundary work as an ever present dilemma requiring continuous negotiation; and encourage individuals and organizations to recognize conflicting perspectives inherent in the leadership assignment, in order to decrease harmful negotiations between them. Such awareness would benefit more sustainable management of healthcare practice. ORIGINALITY/VALUE: This paper highlights how managers can handle ever-present boundary dilemmas in the healthcare sector by regulating their time commitments in various ways. PMID- 22043655 TI - On tooth movements and associated tissue alterations related to edentulous areas and bone defects. AB - The aim of the thesis was to study orthodontic tooth movement in relation to edentulous areas and infrabony pockets as well as the physiological movement of teeth facing an edentulous area. A dog model was used in Studies I and II. Teeth were orthodontically moved into and out from inflamed, infrabony periodontal pockets (Study I) and into areas of reduced bone height (Study II). Clinical, radiographic and histometric analyses were made with respect to changes in tooth supporting tissues. Study III involved clinical, radiographic and 3D model assessments of changes in periodontal conditions and alveolar ridge dimensions in adult patients subjected to tooth movement into areas with reduced ridge dimensions. In Study IV, panoramic radiographs of 292 subjects, taken at an interval of 12 years, were analyzed with regard to changes in the elongation of unopposed molars and tipping of molars facing a mesial edentulous space. In the animal study orthodontic bodily movement of teeth with inflamed, infrabony pockets caused an enhanced rate of progression of the periodontal lesion (Study 1), particularly when the tooth movement was directed towards the infrabony defect. Teeth with healthy periodontium that were orthodontically moved into areas of markedly reduced bone height maintained their periodontal tissue support (Study II). Corresponding orthodontic tooth movement in humans (Study III) resulted in minor dimensional alterations of the periodontal tissues and an increased bucco-lingual width of the alveolar ridge in the area into which the tooth had been moved, whereas a decreased width of the newly established edentulous area was noted. All teeth that were moved showed lateral root resorption at the level of the bone crest on the pressure side, but signs of repair were noticed 1-year post-treatment. In the 12-year radiographic study (Study IV) unopposed molars showed a significant increase in elongation over the 12 years of follow-up. The degree of elongation increased with decreased bone support. Neither edentulous space nor alveolar bone level were found to have a significant effect on tipping. In the presence of both conditions, unopposed molars and molars facing a mesial edentulous space, an increase in elongation was associated with tipping. PMID- 22043656 TI - [The meaning of "apology": the survivors of Nazi medical crimes and the Max Planck Society]. AB - Around the turn of the twenty-first century a new practice in international politics became established: representatives of political, economic and religious organisations apologised for the historical and political crimes of their own collectives, addressing the victims or the victims' descendants. At a public event in June 2001, a formal apology of this kind was made by the president of the Max Planck Society (MPS), who had previously launched an extensive programme of research into the National Socialist history of what was then the Kaiser Wilhelm Society. The majority of the eight invited survivors of human experimentation in Nazi concentration camps refused forgiveness. Instead, they called for the MPS not to content itself with historical research and analysis, but to ensure the continued remembrance of the victims and their suffering. Starting from this 2001 ritual of repentance, the paper examines the participants' diverse views of how to deal with the medical crimes of National Socialism, and asks about possibilities of going beyond historical retrospection to fulfil the imperative of remembrance. PMID- 22043657 TI - [Ants and aliens. An episode in the history of entomological and sociological construction of knowledge]. AB - The frequent use of biological metaphors in descriptions of society is well known and has already been investigated. Even the traces of biological theory in sociology have been explored. In this field of science, studies of social insects play an important role, because ants, bees, and termites have been considered to be genuinely political animals and founders of societies. Like men, social insects exist only in collectives; thus, the entomologist's research directs him from the individual insect, its morphology and taxonomy to the analysis of insect societies. Entomologists like Wheeler or Wilson become sociologists and develop methods to deal with a society whose members are dumb, soulless, without reason, rational choice, or motives. Tools invented to describe the evolution of insect societies have been picked up by sociological founders of systems theory like Parsons or Luhmann, who were busy building a theory of a society, which for heuristic reasons is not composed of men (individuals with souls, motives, consciousness and so on) but rather of communications, media, or codes. My paper treats 1.) the genealogy of this discursive mixture of problems, methods, and focuses on 2.) the rhetorical dimension of this entomological-sociological passage. I will sketch certain 'evident' pictures of society, which function as media of a subliminal crossing of entomological and sociological premises, models, and assumptions. Both can be found in novels like Wilson's Anthill, which this paper analyzes with respect to the concepts of society implied by them, that is, concepts whose blueprints are based on models of an ant society. PMID- 22043658 TI - ["He corrects my view and develops it further." Comments by David von Hansemann on the monograph by Theodor Boveri Concerning the origin of malignant tumors (1914)]. AB - According to many authors, the treatise on cancer written by Theodor Boveri in 1914 demonstrates astonishing foresight with respect to contemporary cancer research, in particular with respect to the genomic instability of tumors. In some recent publications, however, it has been claimed that not Boveri but primarily David von Hansemann deserves credit for these chromosomal theories of cancer origin. The claim seems to be unjustified because there are great differences, both in conception and in argumentation, between both opinions. In addition, it has been ignored that von Hansemann himself said that his views "were corrected and developed further by Boveri". In this paper two obviously unknown comments regarding Boveri's theory by von Hansemann are presented as examples. Furthermore, the paper points out that the pathologist von Hansemann was engaged in the formal genesis of tumors using descriptive methods. By contrast, the embryologist Boveri developed his hypotheses on the basis of the experimentally founded chromosome theory of inheritance in an attempt to explain the etiology or causal genesis of tumors. Thus, it can be concluded that Boveri developed the first genetic cancer theory in the history of medicine. PMID- 22043659 TI - Exploring Greenland: science and technology in Cold War settings. AB - This paper explores a vacant spot in the Cold War history of science: the development of research activities in the physical environmental sciences and in nuclear science and technology in Greenland. In the post-war period, scientific exploration of the polar areas became a strategically important element in American and Soviet defence policy. Particularly geophysical fields like meteorology, geology, seismology, oceanography, and others profited greatly from military interest. While Denmark maintained formal sovereignty over Greenland, research activities were strongly dominated by U.S. military interests. This paper sets out to summarize the limited current state of knowledge about activities in the environmental physical sciences in Greenland and their entanglement with military, geopolitical, and colonial interests of both the USA and Denmark. We describe geophysical research in the Cold War in Greenland as a multidimensional colonial endeavour. In a period of decolonization after World War II, Greenland, being a Danish colony, became additionally colonized by the American military. Concurrently, in a period of emerging scientific internationalism, the U.S. military "colonized" geophysical research in the Arctic, which increasingly became subject to military directions, culture, and rules. PMID- 22043660 TI - The history of Italian psychiatry during Fascism. AB - Specific features characterized Italian psychiatry during Fascism (1922-45), distinguishing it from Nazi psychiatry and giving rise to different operational outcomes, so we have investigated the state of Italian psychiatry during this period. We review the historical situation that preceded it and describe the social and health policies that Fascism introduced following new legislative and regulatory acts. We examine the preventive and therapeutic role played by psychiatry (the electric shock was an Italian invention) and, thanks to the Enciclopedia Italiano published during those years, we are able to highlight psychiatry's relationship to psychology, psychoanalysis, philosophy and religion. The shortcomings of Italian psychiatric research and practice are also seen in terms of what the State failed to do rather than what it did. PMID- 22043661 TI - The mental health sector and the social sciences in post- World War II USA. Part 2: The impact of federal research funding and the drugs revolution. AB - The second of two linked papers examining the interactions of psychiatry and the social sciences since World War II examines the role of NIMH on these disciplines. It analyses the effects of the prominence and the decline of psychoanalysis, and the impact of the psychotropic drugs revolution and the associated rise of biological psychiatry on relations between psychiatry and clinical psychology; and it explores the changing relationships between psychiatry and sociology, from collaboration to conflict to mutual disdain. PMID- 22043662 TI - Insanity and ethnicity in New Zealand: Maori encounters with the Auckland Mental Hospital, 1860-1900. AB - This article examines Maori patients at the Auckland Mental Hospital between 1860 and 1900.We argue that the patient case notes reveal 'European' categories in which Maori were situated, and demonstrate the extent to which the authorities at the hospital grappled with their appearance, their language and their culture, all of which were elements of their ethnicity. We argue that the use of institutional case records is highly suggestive of some of the historical meanings of insanity for Maori, including the lack of detailed or sustained collection of information about patients' tribal affiliations, the interest shown in their rights to land in maintenance payment inquiries, the experiences of cultural alienation or mate Maori, and the sad outcomes for Maori. PMID- 22043663 TI - The American Psychiatric Association and the history of psychiatry. AB - The history committee within the American Psychiatric Association was actively involved in the history of psychiatry in the early decades of the twentieth century, as well as from 1942 to 2009.This paper explores the role of this committee in the context of changes in the psychiatric profession over the twentieth century. PMID- 22043664 TI - What is a'mood-congruent' delusion? History and conceptual problems. AB - This article investigates the history of the concept of mood-congruent delusions and the problems accompanying this concept. In the late nineteenth century, there were conflicting views regarding the relationship between the contents of an individual's delusional thought and his/her affective state. The differentiation between delusion-like ideas secondary to affective state and incomprehensible primary delusions was introduced in the early twentieth century; this differentiation is the origin of the present-day distinction between mood congruent and -incongruent delusions. Although the themes of delusions are clearly described in the operational diagnostic criteria for mood-congruent psychotic symptoms, the concept of mood congruence inevitably involves ambiguity. This article argues that a dilemma between reliability and validity emerges when diagnosing mood-congruent (and -incongruent) psychotic symptoms. PMID- 22043665 TI - Evacuation and deprivation: the wartime experience of the Devon and Exeter City Mental Hospitals. AB - In Exeter, the need for space to treat casualties in World War II led to a significant reduction in capacity at one psychiatric hospital and the closure of another. In spite of this, inpatient stays were longer than in peacetime, partly due to relatives who had to weigh up the advantages and disadvantages of having their unwell kin returned to them. In the latter years of the war, admissions from the Devon catchment area were higher than in peacetime. Having more patients who stayed longer was largely compensated for by utilizing free space as opposed to reducing admissions, leading to overcrowding and a restricted inpatient regime. PMID- 22043666 TI - [Fresh water macroinvertebrates of Costa Rica I]. AB - This is the first in a series of three volumes on the freshwater macroinvertebrates of Costa Rica. The present volume includes an introductory chapter summarizing the major types of freshwater environments, the biology of freshwater macroinvertebrates (habitats, food, respiration, osmoregulation, etc.), ecological and economic importance, conservation and a synopis of the major groups, followed by a simplified key. The next two chapters discuss collecting methods and biomonitoring. These are followed by chapters on mayflies (Ephemeroptera: 10 families), dragonflies (Odonata: 13 families), stoneflies (Plecoptera: 1 family) and caddisflies (Trichoptera: 15 families). Both in this volume and in those to follow, the chapters treating individual taxa include a summary of the natural history, importance, taxonomy, collecting methods, morphology and an illustrated key to the families; each family is discussed separately and an illustrated key to genera is provided; each chapter ends with a bibliography and a table listing all the genera with information on number of species, distribution, habitat and tolerance to water pollution. While the emphasis is on families and genera known from Costa Rica, additional taxa occurring elsewhere in Central America are mentioned. The present volume also includes numerous color plates of aquatic macroinvertebrates. PMID- 22043667 TI - [Characteristic of moxibustion and its warming-dredging effect]. AB - Through the analysis on warming stimulation at moxa sites and the inflammatory purulent phenomenon by moxibustion, the author points out that moxibustion promotes qi and blood circulation is it's effective feature. It is viewed that "warming and dredging" is the high summarization of moxibustion effect. Moxibustion acts on expelling cold, promoting the circulation in meridian and collateral, clearing away heat, detoxification, strengthening the antipathogenic qi, preventing from diseases and healthcare, etc. All of these functions depend on the effect of moxibustion for circulating qi and blood flow. Hence, "warming and dredging" is the nature of moxibustion. PMID- 22043668 TI - [Periarthritis of shoulder treated with deep puncture by elongated needle combined with spike-hooked needle and cupping: a multicentral randomized controlled study]. AB - OBJECTIVE: To assess the clinical efficacy and the safety for periarthritis of shoulder treated with deep puncture by elongated needle combined with spike hooked needle and cupping. METHODS: A multicentral randomized controlled study was adopted. One hundred and twenty cases were divided into an observation group and a control group, 60 cases in each one. In observation group, elongated needle, spike-hooked needle and cupping were used to stimulate Jianyu (LI 15), Naoshu (SI 10), Naohui (TE 13) and Jianqian (Extra). In control group, a conventional needling and cupping were applied to the same points as observation group. Visual Analogue Scale (VAS) and Melle evaluation for the function activity of shoulder joint were adopted to assess and compare the efficacy on analgesia and the effect on shoulder joint range of motion before and after treatment in two groups. RESULTS: In observation group, the cured and markedly effective rate of analgesia was 91.7% (55/60), which was obviously better than 20.4% (12/59) in control group (P < 0.001). Concerning to the improvements of the range of motion in shoulder joint, the cured and markedly effective rate in observation group was 91.7% (55/60), which was better than 18. 6% (11/59) in control group (P < 0.001). VAS score and Melle score after treatment were apparently improved as compared with those before treatment in two groups (all P < 0.001). The improvements in observation group were superior to those in control group (both P < 0.001). There was no adverse event reported during the treatment in two groups. CONCLUSION: The deep puncture by elongated needle combined with spike-hooked needle and cupping achieves a significant clinical efficacy on periarthritis of shoulder and has no adverse reaction reported. PMID- 22043669 TI - [Acupuncture at Jiaji (EX-B2) for 40 cases of allergic rhinitis]. PMID- 22043670 TI - [Clinical curative effect and factor analysis of depression treated by acupuncture]. AB - OBJECTIVE: To evaluate the curative effect of primary depression treated with the main points of Back-shu points of Five-zang and Geshu (BL 17) according to the differentiation. METHODS: Sixty cases of primary depression were randomly divided into an acupuncture group (31 cases) and a western medication group (29 cases). In acupuncture group, Back-shu points of Five-zang and Geshu (BL 17) were applied as the main points, Taichong (LR 3) and Sanyinjiao (SP 6) were added for stagnation of liver qi and spleen deficiency; Shenmen (HT 7) and Sanyinjiao (SP 6) were added for deficiency of both heart and spleen according to the differentiation. In western medication group, Fluoxetine Hydrochloride capsule was taken by oral administration for 20 mg, once a day. The treatment lasted for 6 weeks in both groups. After 2, 4, and 6 weeks treatment, the clinical curative effects of both groups were assessed by Hamilton Depression (HAMD) Rating Scale, HAMD Factor Analysis and Asberg Side Effect Scale. RESULTS: After 6 weeks treatment, the total effective rate was 67.7% (21/31) in acupuncture group and 65.5% (19/29) in western medication group, indicating the close curative effects(P > 0.05). After 2, 4, and 6 weeks treatment, the HAMD score, scores of anxious somatization, sleeping and retardation factors were significantly reduced (all P < 0.01) in two groups, through the comparison at different time points between two groups, scores of anxious somatization, sleeping factors in acupuncture group were superior to those in western medication group (both P < 0.05), but score of retardation factor in western medication group was superior to that in acupuncture group (P < 0.05). The Asberg Side Effect Scale in western medication group arrived at peak at thesecond week, and then reduced slowly; the side effect in acupuncture group was low and steady, and lower than that in western medication group after 6 week treatment (P < 0.05). CONCLUSION: The curative effect of depression with acupuncture based on differentiation is equal to that of Fluoxetine Hydrochloride capsule with oral administration, while the side effect is milder than that of Fluoxetine Hydrochloride capsule. PMID- 22043671 TI - [Primary optimization of acupuncture program for dysphagia after cerebral infarction]. AB - OBJECTIVE: To optimize primarily acupuncture program for dysphagia after cerebral infarction. METHODS: Sixty-three patients with pseudobulbar palsy dysphasia after cerebral infarction were selected as the subjects. Water swallow test was adopted for observation index. Orthogonal design was used to study the different combinations of treatment programs among four factors and three levels, named acupuncture opportunity (factor A: A1: 1-10 d, A2: 11-20 d, A3: 21-40 d), point combination (factor B: B1: points in the neck, B2: points in the neck + points in the glossopharyngeal part, B3: points in the neck + points in the glossopharyngeal part + differentiating point), needling depth (factor C: C1: shallow puncture, C2: moderate puncture, C3: deep puncture), and treatment session (factor D: D1: 2 sessions, D2: 4 sessions, D3: 6 sessions); as well as the influences on pseudobulbar palsy dysphagia after cerebral infarction so as to determine primarily the optimized acupuncture program for dysphagia after cerebral infarction. RESULTS: The direct analysis of orthogonal design indicated that the best level and the combination of four factors and three levels were A1 (or A2), B3, C3 and D3. It meant that for the patients less than 20 days for sickness, the points in the neck, points in the glossopharyngeal part and points selected according to syndrome differentiation were selected for deep puncture and the treatment lasted for 6 sessions. This program achieved the best improvement in water swallow test. The comparison between the primary effect and secondary effect among four factors (variance analysis) showed that factor A and C were the significant factors (P < 0.05), factor B and D were not significant (P > 0.05). It was suggested that acupuncture opportunity and needling depth played the significant roles in clinical efficacy. The comparison among different levels in terms of the significant factors A and C (multiple comparison) presented that A1 and A2 were superiorly significant than A3 (P < 0.001), A1 was not different in significance from A2 (P > 0.05). C3 was superiorly significant than C2 and C1 (P < 0.001, P < 0.01) and C2 was superiorly significant than C1 (P < 0.05). CONCLUSION: By the comprehensive summarization of direct analysis, variance analysis and multiple comparison combined with actual clinical situation, the optimal program of acupuncture treatment for pseudobulbar palsy dysphasia after cerebral infarction is that in terms of the four factors and three levels, for the patients within 1 to 20 days for sickness, acupuncture is applied to the points in the neck or combined with points in the glossopbaryngeal part or the points se-i lected according to syndrome differentiation, with deep puncture, for 4 to 6 sessions of treatment. PMID- 22043672 TI - [Comparation of effect and cost-benefit analysis between acupoint catgut embedding and electroacupuncture on simple obesity]. AB - OBJECTIVE: To compare the clinical effect of acupoint catgut-embedding and electroacupuncture on simple obesity and evaluate the economics benefit by cost benefit analysis. METHODS: Sixty cases were randomly devided into an acupoint catgut-embedding group and an electroacupuncture group, 30 cases in each group. Zhongwan (CV 12), Tianshu (ST 25), Daheng (SP 15), Shuifen (CV 9), Qihai (CV 6), Guanyuan (CV 4), Zusanli (ST 36) and Ashi acupoints were selected as the main acupoints in both groups. The acupoint catgut-embedding group was treated with acupoint catgut-embedding, once each week, four weeks as a course for two courses. The electroacupuncture group was treated with electroacupuncture, three times each week for eight weeks. RESULTS: 1) The total effective rate in the acupoint catgut-embedding group was 90.0% (27/30) and in the electroacupuncture group was 86.7% (26/30), with the similar therapeutic effect between the two groups (P > 0.05). 2) The body mass, body mass index (BMI), waistline, hip circumference and waist-to-hip ratio in the two groups were all decreased significantly (all P < 0.05). 3) The total medical treatment cost in the acupoint catgut-embedding group was 61 500 yuan and the cost per patient was 2050 yuan, and in the electroacupuncture group, the total cost was 117 210 yuan and the cost per patient was 3907 yuan. The cost effect analysis showed that there were 1857 yuan of the cost per patient in the acupoint catgut-embedding group less than that in the electroacupuncture group. CONCLUSION: Acupoint catgut-embedding has significant effect in treating simple obesity with low cost and fine economics benefit. PMID- 22043673 TI - [Clinical observation on time-dependent analgesic effect of acupuncture at Jiaji (EX-B 2) combined with superficial needling for lumbar disc herniation]. AB - OBJECTIVE: To observe the difference of the therapeutic effect of acupuncture at Jiaji (EX-B 2) combined with superficial needling for lumbar disc herniation (LDH) and to explore the synergy effect between acupuncture at Jiaji (EX-B 2) and superficial needling. METHODS: Sixty patients with LDH were randomly divided into an observation group and a control group, 30 cases in each group. The observation group was treated with superficial needling at the corresponding myofascial fasciae trigger point (MTrP) and leave the plastic tube in the body for 6 hours, and then acupuncture at Jiaji (EX-B 2) and the needle was remained for 30 min. The control group was treated with superficial needling simply. Both groups were treated once daily, five days in succession with 2 days interval, 10 times constituting a treating course for 2 courses. The average onset time of analgesic effect and the effect-lasting time after the first treatment were observed. The mean pain scores after the first treatment and after two treatment courses were compared by McGill pain inquire scale. RESULTS: There was no significant difference in the average onset time of the two groups [(5.10 +/- 3.70) min vs (5.93 +/- 5.09) min, P > 0.05]. But the effect-lasting time of (13.00 +/- 6.90) h in the observation group was longer than that of (6.27 +/- 3.98) h in the control group (P < 0.01). Compared with the scores of Pain Rating Index (PRI), Visual Analogue Scale (VAS) and Present Pain Intensity (PPI) after the first treatment, there were no significant statistical differences between the two groups (all P > 0.05). But the same comparison after 2 treating courses showed that the scores of PRI, VAS and PPI in the observation group were lower than the control group (all P < 0.01). CONCLUSION: Acupuncture at Jiaji (EX-B 2) can extend the analgesic time and enhance the analgesic effect of the superficial needling. PMID- 22043674 TI - [Dynamic moxibustion combined with acupuncture for 35 cases of lumbar disc herniation]. PMID- 22043675 TI - [Comparative research on effect of warm needling therapy on pulmonary function and life quality of patients with COPD in the stable phase]. AB - OBJECTIVE: To observe the effects on chronic obstructive pulmonary disease (COPD) in the stable phase treated with warm needling therapy and Seretide. To make the comparison of improvements between two therapies in terms of the clinical symptoms and life quality. METHODS: Sixty cases were randomly divided into a warm needling group and a Seretide group, 30 cases in each one. In warm needling group, acupuncture with filiform needle was applied mainly to Dingchuan (EX-B 1), Feishu (BL 13) and Zusanli (ST 36). Warm needling therapy was supplemented on back-shu point and Zusanli (ST 36), once every other day, thrice each week. In Seretide group, Seretide inhalant was applied, one inhalation, 2 times each day. After 8-week treatment, the changes in pulmonary function such as forced expiratory volume in the first second (FEV1), clinical symptoms, and the score of St George's Respiratory Questionnaire (SGRQ) were observed in two groups and the comparison of them was conducted between groups and within each group. RESULTS: The pulmonary function indices such as FEV1 were all improved effectively in two groups (all P < 0.05). After 4-week treatment, the improvement in respiratory symptoms was superior in Seretide group as compared with warm needling group (P < 0.05). In terms of the improvement in general symptoms such as chills and fever, the result in warm needling group was better than that in Seretide group (P < 0.05). The efficacies were similar between two groups in 8-week treatment. Concerning to the improvement of life quality, the result in warm needling group was slightly better than that in Seretide group (the improvement value 12.8413.43 vs 10.21 +/- 3.89, P < 0.05). CONCLUSION: Warm needling therapy improves the pulmonary function of the patients with COPD in the stable phase, releases clinical symptoms and improves life quality. Its effects are similar to those of Seretide. PMID- 22043676 TI - [Error recognition of branches of meridians]. PMID- 22043677 TI - [Effect of moxibustion at Sanyinjiao (SP 6) on delivery stage and postpartum bleeding of primipara]. AB - OBJECTIVE: To observe the effect of moxibustion at Sanyinjiao (SP 6) on delivery stage of primipara. METHODS: Sixty cases of primipara were divided into a moxibustion at Sanyinjiao group, a non-acupoint group and a blank group. When the diameter of wormb mouth opened to 2-3 cm, showing that it entered into active stage of uterine contraction, moxibustion at Sanyinjiao (SP 6) for primipara was applied in moxibustion at Sanyinjiao group; moxibustion was applied at 1 cun towards radialis from the region where 2 cun above Kongzui (LU 6) in non-acupoint group, 30 minutes treatment was for both groups. There was no intervention in blank group. After delivery, the time of first,second and third delivery stages and postpartum bleeding 2 hours after delivery were compared among three groups. RESULTS: The active duration of first delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (P < 0.05, P < 0.01); the duration of the second delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (both P < 0.05) as well; the postpartum bleeding 2 hours after delivery in moxibustion at Sanyinjiao group was less than other two groups and the difference was statistic significant between moxibustion at Sanyinjiao group and blank group (P < 0.05). CONCLUSION: By moxibustion at Sanyinjiao (SP 6), the active duration of first delivery stage and the duration of second delivery stage are markedly shortened, postpartum bleeding 2 hours after delivery is obviously reduced, and the safety of vaginal delivery is increased. PMID- 22043678 TI - [Observation of curative effect of herpes zoster treated with acupuncture based on syndrome differentiation combined with pricking and cupping]. AB - OBJECTIVE: To compare the differences of curative effects of herpes zoster treated with acupuncture based on syndrome differentiation combined with pricking and cupping and simple pricking and cupping. METHODS: Eighty-six cases were randomly divided into an observation group (43 cases) and a control group (43 cases). In observation group, acupoints selection based on syndrome differentiation i.e. Quchi (LI 11), Zusanli (ST 36), Sanyinjiao (SP 6), etc. were selected and pricking and cupping at affected parts were applied, and the cases were classified into damp heat in liver and gallbladder, damp retention and spleen deficiency, and qi deficiency and blood stasis. In control group, all the cases were simplely treated with pricking and cupping at affected parts. The treatment was given once a day, and seven days were made one session. The curative effect was evaluated after 2 courses, and the follow-up was carried on after 1 month. RESULTS: The cured and markedly effective rate was 93.0% (40/43) in observation group, superior to that of 67.4% (29/43) in control group (P < 0.01). Postherpetic neuralgia: there was 2.3% (1/43) in observation group, inferior to that of 14.0% (6/43) in control group. Comparison in 3 types: the cured and markedly effective rate of damp heat in liver and gallbladder: 94.7% (18/19) in observation group, and 85.7% (18/21) in control group, showing no significant difference between groups (P > 0.05). The cured and markedly effective rate of damp retention and spleen deficiency: 93.8% (15/16) in observation group, superior to that of 60.0% (9/15) in control group (P < 0. 05). The cured and markedly effective rate of qi deficiency and blood stasis: 87.5% (7/8) in observation group, superior to that of 28.6% (2/7) in control group (P < 0.05). CONCLUSION: For herpes zoster, acupoints selection based on syndrome differentiation combined with pricking and cupping therapy is high pertinent and effective, the postherpetic neuralgia can be reduced significantly and the curative effect is superior to that of simple pricking and cupping. PMID- 22043679 TI - [Effect of acupoints with different tissue on electroacupuncture sensation]. AB - OBJECTIVE: To evaluate the influence on frequency, intensity and the amount of current flow produced by electroacupuncture sensation of acupoints with different distributions (meridian category, tissue type and nerve innervations). METHODS: Twenty-one healthy volunteers were enrolled. According to the different tissue of acupoints, paired acupoints were grouped: Zusanli (ST 36) vs Yanglingquan (GB 34) (different meridian categories), Neiguan (PC 6) vs Daling (PC 7) (different tissue types), Zusanli (ST 36) vs Shuidao (ST 28) (different nerve innervations), Guanyuan (CV 4) vs Zhongwan (CV 12) (different nerve innervations), and Zusanli (ST 36) vs Guanyuan (CV 4) (different meridian categories, tissue types and nerve innervations). The electric frequency was 15 Hz. The electric current was under the participant's tolerance without sharp pain; the electroacupuncture was applied for three times with interval, 90 seconds totally. Soreness, numbness, fullness, heaviness, tingling, pressure, dull pain, warmness, coolness and amount of current flow were recorded, and the frequency, intensity and current amount between the paired acupoints were compared. RESULTS: There were no significant differences in frequency of needling sensations between paired points (all P > 0.05). In the 9 electroacupuncture sensations, fullness, numbness and soreness were most commonly seen and obvious, heaviness, pressure and tingling came second, and dull pain, warmness, and coolness occurred at lower frequency. There were differences in the intensity of acupuncture sensation between paired acupoints in part of them, the soreness, fullness and heaviness at Zusanli (ST 36) were stronger than those at Shuidao (ST 28) (all P < 0.05 ); fullness and numbness at Zusanli (ST 36) were stronger than those at Guanyuan (CV 4) (both P < 0.01); fullness at Guanyuan (CV 4) was stronger than that at Zhongwan (CV 12) (P < 0.05 ); the current flow of electroacupuncture was similar between paired acupoints (all P > 0.05). CONCLUSION: In the situation that there is no obvious difference in amount of current flow caused by electroacu puncture sensation, the obvious correlations between frequency of electroacupuncture sensation and tissue properties of acupoints are not appeared, and the difference of sensation intensity between paired acupoints may be associated with different nerve innervations. The frequency and intensity of electroacupuncture sensation at one acupoint are stable at different times. PMID- 22043680 TI - [Observation of effect on contraction function of gallbladde by acupuncture at Jianjing (GB 21)]. AB - OBJECTIVE: By B ultrasound, the changes of contraction function of gallbladder by acupuncture at Jianjing (GB 21) were observed and the internal relations between Jianjing (GB 21) and cholecystitis were explored, in order to explore the better therapy. METHODS: Two hundreds cases who had been diagnosed as cholecystitis (acalculous cholecystitis) were classified in observation group, including gallbladder expanding (84 cases) and gallbladder constricting (116 cases); 100 cases who had examined as healthy were taken in control group. Acupuncture at Jianjing (GB 21) on right shoulder was applied in both groups. Through B ultrasound examination, the changes of gallbladder volume in both groups were compared before acupuncture, 15 min after needle insertion and 30 min after needle withdrawing. RESULTS: The gallbladder volume of gallbladder expanding and gallbladder constricting cases were constricted or expanded 15 min after needle insertion and 30 min after needle withdrawing, and there were statistical significances (all P < 0.01). Compared the outcomes at different time points after acupuncture with that before acupuncture, the changes of gallbladder constricting were unobvious (both P > 0.05) in control group. In observation group, the pain relief rate for 142 cases companied with shoulder and back pain was 98.6% (140/142). CONCLUSION: Acupuncture at Jianjing (GB 21) can improve the gallbladder constricting, regulate bidirectional function of expanding and constricting, and efficiently relieve shoulder and back pain. PMID- 22043681 TI - [Molecular mechanism of acupoint catgut-embedding for experimental colitis in rats]. AB - OBJECTIVE: To explore the effect and its mechanism of acupoint catgut-embedding for experimental colitis in rats. METHODS: Eighteen SD rats were randomly divided into a normal control (NC) group, a model (MO) group and a acupoint catgut embedding (AC) group, 6 rats in each group. Animals in MO group and AC group were treated by trinitro-benzene-sulfonic acid (TNBS) to establish model with colitis. No other treatment was given to the rats in MO group, but acupoint catgut embedding was implanted at "Shangjuxu" (ST 37), "Tianshu" (ST 25) and "Dachangshu" (BL 25) in the rats in AC group. The symptoms of diarrhea and bloody stool, and histopathology changes in colon were observed 15 days after the treatment. Expression of IL-17, beta2AR, NFkappaBp65 were observed by immunohistochemistry. Expressions of NF-kappaBp65 and beta2AR in splenic lymphocyte were detected by the Western blot method. RESULTS: Diarrhea and mucus bloody purulent stool were soon controlled, and colon mucosa injures were obviously improved in AC group. The NF-kappaBp65 value in splenic lymphocytes of 249.70 +/- 13.66 in MO) group was higher than 86.22 +/- 8.09 in NC group (P < 0.01), and 219.02 +/- 7.42 in AC group was less than that in MO group (P < 0.01). The expression of beta2AR in splenic lymphocytes of 594.97 +/- 173.22 in MO group was less than 957.45 +/- 171.56 in NC group (P < 0.01), and 1335.93 +/- 244.34 in AC group was higher than that in MO group (P < 0.01). The expression of IL-17 in colon mucosa in MO group was increased, while the expression of IL-17 in colon mucosa in AC group was decreased. CONCLUSION: Acupoint catgut-embedding at Shangjuxu (ST 37), Tianshu (ST 25) and Dachangshu (BL 25) has obviously effect in treating experimental colitis and the mechanism may be related to regulate the expression of IL-17, beta2AR and NF-kappaBp65. PMID- 22043682 TI - [Selection points by up-down cross method for ankle sprain]. PMID- 22043683 TI - [Twenty-one cases of pain caused by earthquake treated mainly with acupuncture at Jiaji (EX-B 2)]. PMID- 22043684 TI - [Current situations and thinking of acupuncture and moxibustion in Jordan]. AB - The brief history of acupuncture, its current situation, locations for acupuncture practitioners, the manipulation and indications of acupuncture in Jordan are introduced in this paper. The acupuncture treatment in Jordan started in the early 1990s. Now there are more than 20 private acupuncture clinics in different size, most in the capital city of Amman. Acupuncture practitioners are western doctors who studied acupuncture techniques in China. The indications of acupuncture in Jordan are pain and nervous system diseases. Acupuncture therapy can be applied single or combined with physical therapy. PMID- 22043685 TI - [Acupuncture at Governor Vessel points for 50 cases of facial spasm]. PMID- 22043686 TI - [Development and prospects of acupuncture therapy in Eritrea]. AB - It has been over 30 years that acupuncture was first introduced and later used to treat patients in Eritrea. There are acupuncture clinics at three hospitals to treat various common diseases. As one of the valuable treatments to cure diseases, acupuncture has been accepted by the government and the public in Eritrea. It is the fruits of public recognition, government support and the devotion of Chinese clinic practitioners. PMID- 22043687 TI - [Acupuncture at "cervical three points" combined with meridian syndrome differentiation for 60 cases of cervical spondylosis of nerve root type]. PMID- 22043688 TI - [Rethinking on Ashi points]. AB - Textual research on the naming of Ashi points is carried out. And it is clarified that Ashi points are not pain "pain points". According to various comprehensions of ancient and modern physicians, it is approved that Ashi points include points of 14 meridians and extra points. And it is also concluded through exploration of essence of Ashi points that needling sensation of Ashi points is the same with regular points and extra points. PMID- 22043689 TI - [Acupuncture combined with finger cupping therapy for Raynaud's disease]. PMID- 22043690 TI - [Study on the mechanisms of cupping therapy]. AB - Computerized literature searches are performed for articles of the mechanism of cupping therapy in the past 10 years. The mechanism of action of local negative pressure applied to human body is studied in terms of specific changes in local tissue structure, stretch to the nerve and muscle, increasing blood circulation and causing autohemolysis. This paper aims to explain the mechanism of cupping therapy according to modern science. PMID- 22043691 TI - [Acupoint injection of thymopeptide for 64 cases of repeated respiratory infection in adults]. PMID- 22043692 TI - [Modern documentary research on disease menu of acupuncture-moxibustion for mental and behavioral disorder]. AB - OBJECTIVE: Dominant disease menu of mental and behavioral disorder of acupuncture therapy was summarized and obtained in this article. METHODS: Literatures on clinical treatment of mental and behavioral disorder with acupuncture were picked up from CBMdisc and CNKI during 1978 to 2007. Types of mental and behavioral disorder and report frequency of each disease treated with acupuncture were counted. And dominant diseases which were favorable to be treated with acupuncture were acquired through analysis and inductive method. RESULTS: Twenty nine diseases of mental and behavioral disorder are favorable to be treated with acupuncture which were mentioned in totally 1967 related documents. It is found that the number of reports of sleep disorder, depression, hysteria aphronesia, dementia and sexual disorder are ranked as the top five. CONCLUSION: It is concluded that the preponderant diseases of mental and behavioral disorder treated by acupuncture are dementia, withdrawal syndrome, mental retardation, obsessive-compulsive disorder, sleep disorder, gastrointestinal neurosis (gastrointestinal disorders), depression, alcoholism and globus hystericus. PMID- 22043693 TI - [Analysis of the distribution of diseases in 6435 inpatients from the department of acupuncture and moxibustion]. AB - OBJECTIVE: To understand the distribution of diseases in inpatients from the department of acupuncture and moxibustion and to provide the references for the scientific research direction of acupuncture and moxibustion. METHODS: By use of information management system of the medical records, the first page of the medical record of 6435 cases from January 1, 2003 to December 31, 2010 was extracted. RESULTS: It shows a clear upward trend in the department of acupuncture and moxibustion in 8 years. The vast majority are elderly patients in 6435 cases, involving in 309 kinds of diseases, the major cases focus on the diseases of motor system and cerebrovascular system. The top 10 ranking of diseases and the rates are lumbar spondylosis (17.73%), cerebral infarction (13.77%), cervical spondylosis (13.66%), sequelae of cerebral infarction (7.47%), lumbar disc herniaion (4. 41%), osteoarthropathia (3.40%), cerebral hemorrhage (2.91%), herpes zoster (2.33%), postherpetic neuralgia (2.33%), sequelae of cerebral hemorrhage (2.32%). CONCLUSION: The people's acceptance of acupuncture and moxibustion is increasing and the sufferers treated by acupuncture and moxibustion are mostly elderly patients. The research on the motor system diseases and cerebrovascular diseases should be strengthened. PMID- 22043694 TI - [Wrist-ankle acupuncture for 30 cases of pure sensory stroke]. PMID- 22043695 TI - [Case analysis on problem-based learning of acupuncture: "a turning round before birth"]. AB - "A turning round before birth" is a problem-based learning (PBL) case in Chinese medicine education. It focuses on malposition of fetus, through discussion on a series of questions, types and causative factors of malposition of fetus could be comprehended, diagnostic time and methods are set up, and manipulations of moxibustion at Zhiyin (BL 67) for malposition of fetus can be mastered. Mechanism on position correction is explored, and key points in application are clarified. Therefore, methods of position correction with easy, safe and effective manipulations can be popularized as well as the PBL methods in education of Chinese medicine. PMID- 22043696 TI - [Long snake moxibustion at Governor Vessel in dog-days for 58 cases of ankylosing spondylitis]. PMID- 22043697 TI - [Shape and functions of shear needle in Internal Classic]. AB - The shape of shear needle mentioned in Internal Classic was explored according to the available documents and the unearthed relics. And the functions of shear needle were studied as well. It is held that the initial shape of shear needle is the imitation of plowshare. Its head is wide and flat, which is similar to a triangle. And it's base and a hypotenuse form an acute angle with narrow and sharp blades. The blade of the base and the tip of the acute angle is considered as the site of action, which can be applied for fast and superficial insertion or cutting at the local area. It can protect the body from damage of interior tissues, and at the same time, has the function of clearing heat. PMID- 22043698 TI - [Research review on apoplectic urinary incontinence treated with acupuncture moxibustion in recent 5 years]. AB - The relevant documents of apoplectic urinary incontinence treated with acupuncture-moxibustion in recent 5 years have been collated and analyzed in aspect of current situation of acupuncture-moxibustion treatment, acupoint selection, manipulation and problems. The result indicates that the main therapy for this disease is acupuncture-moxibustion combined with electroacupuncture or other methods, and the acupuncture-moxibustion therapy is superior to the medicine. The clinical research has made considerable progress and the great importance has been attached to the research method. The main problems are low credibility of total quality, inconsistent curative course, incomplete case of illness, missing of quality control, disordered standards of clinical diagnosis and curative effect evaluation, varied observation index and phatic discussion of mechanism. It is suggested to carry on scientific research, enhance research lever, expand mind, innovate ideas, and establish uniformed standards of diagnosis and curative effect evaluation and observation index. PMID- 22043699 TI - [Protective effects of astaxanthin against oxidative damage induced by 60Co gamma ray irradiation]. AB - OBJECTIVE: To investigate the protection effect of haematococcus pluvialis (containing astaxanthin) against the impairment of anti-oxidative system and DNA damage in mice induced by 60Co gamma-rays. METHODS: Fifty mice were randomly divided into five groups, i.e. three haematococcus pluvialis groups (41.7, 83.3 and 166.7 mg/kg in vegetable oil, respectively), control group and model group (vegetable oil only). All mice except control group were irradiated by 8 Gy 60Co gamma-rays 30 days later, and executed in the 4th day after irradiation. Liver cells were collected for the analysis of the integrity of DNA by comet assay, as well as MDA contents, SOD and GSH-Px activities in liver by commercial kits. Peripheral granulocyte and bone marrow nucleated cells were counted by hematocyte counter. RESULTS: MDA contents of model group were higher than those of control group (P < 0.01), and SOD, GSH-Px activities of model group were lower than those of control group (P < 0.01). Compared with the model group, MDA contents were decreased (P < 0.01), and SOD and GSH-Px activities were increased (P < 0.01) in all haematococcus pluvialis groups, especially in the high haematococcus pluvialis group, and the more haematococcus pluvialis in the diet of mice, the lower rate of comet tail and OTM value were shown (P < 0.01). Furthermore, the counts of peripheral granulocyte and bone marrow nucleated cells of model group were lower than those of the control group, while the counts of peripheral granulocyte and bone marrow nucleated cells of medium and high haematococcus pluvialis groups were increased significantly when compared with the model group (P < 0.01). CONCLUSION: Astaxanthin might have some protective effect against oxidative impairment and DNA damage induced by 60Co gamma-rays in mice. PMID- 22043700 TI - [Cloning, expression and purification of allergen parvalbumin from Aristichthys nobilis and its allergic activity]. AB - OBJECTIVE: To clone, express and identify the parvalbumin gene from Aristichthys nobilis, and investigate its allergenicity. METHODS: The parvalbumin gene was amplified by RT-PCR and cloned into PMD18-T for sequencing and analysis. Then the target gene was subcloned into pET-28a (+) for expression in E. coli BL21 (DE3) by IPTG induction. The recombinant protein was purified by metal (Ni2+) chelating affinity chromatography. Its allergenicity was examined by Western-blotting assay. RESULTS: The length of gene (Accession No. FJ013047) was 330 bp, coding 109 amino acids. The E. coli strain could express a recombinant protein with a molecular weight of 11 537 Da. The recombinant allergen was identified as its affinity to specific IgE antibodies from the allergic patient sera by Western blotting. CONCLUSION: The parvalbumin gene from Aristichthys nobilis is successfully cloned and expressed in this study, and the recombinant protein possesses good IgE-binding capacity. PMID- 22043701 TI - [Chromosome damage of human bronchial epithelial cells induced by glycidyl methacrylate]. AB - OBJECTIVE: To observed the chromosome damage of human bronchial epithelial cells induced by glycidyl methacrylate (GMA). METHODS: Chromosome aberration analysis of human bronchial epithelial cells treated with GMA at different dosages (4, 8, 12, 16 and 20 microg/ml), times (1, 2 and 3 times), and phases (10th, 30th genetation) was detected. RESULTS: In the dosages range from 4 to 20 microg/ml, the aberration rates (3%, 6%, 7%, 11% and 14%) were demonstrated increasingly with the increase of exposure doses, and dose-effect relationship was found. Significant differences were observed when treated with GMA three times (6%, 7% and 10%). Structure aberrations were found in the transformed 10th-generation cells, while number aberrations were mainly manifested in the transformed 30th generation cells. CONCLUSION: The chromosome aberration can be induced by GMA in the human bronchial epithelial cells, from the structure aberration at the beginning to the lack of normal nuclear style. PMID- 22043702 TI - [Differential analysis of two-dimensional gel electrophoresis profiles in the protective effects of resveratrol on HaCaT cells induced by UVB irradiation]. AB - OBJECTIVE: To analysis the differences of protein expression and possible protective mechanisms of resveratrol (Res) on human keratinocytes (HaCaT cells) irradiated by ultraviolet B (UVB). METHODS: MTT test was used to assay the effects of Res on the proliferation of HaCaT cells. The tested objects were divided into four groups, the control, UVB irradiation, Res intervention and UVB + Res intervention (r-u) groups. Then the protein of cells in the four groups was separated by a two-dimensional gel electrophoresis (2-DE) and the differentially expressed protein spots were identified by MALDI-TOF-MS. RESULTS: Ten differential expressed protein spots were analyzed, and eight kinds of protein were identified. Except for four kinds of uncharacterized protein, the level of Histone H1.2 was up-regulated in UVB group (P < 0.05), the levels of TFIIE-beta and zinc finger were down-regulated in both UVB and r-u groups, and the level of MAGOH was down-regulated significantly in UVB group (P < 0.05). CONCLUSION: The differentially expressed protein spots related to the protection of Res on HaCaT cells irradiated by UVB were found with the two-dimensional gel electrophoresis. PMID- 22043703 TI - [Antagonism effect of MK801 on apoptosis of primary-cultured cortical neuron caused by dimethoate]. AB - OBJECTIVE: To explore the antagonism effect of MK801 on apoptosis of primary cultured cortical neurons caused by dimethoate. METHODS: Cortical neurons were isolated and cultured in serum free medium for 6 days in vitro, then treated with 100 micromol/L dimethoate for 48h. 50 and 100 micromol/L MK801, a N-methyl-D aspartic acid receptor (NMDAR) blocker, were used to intervene 100 micromol/L dimethoate group. HPLC-FLD was taken to measure the concentration of excitatory amino acid. RT-PCR was used to detect transcription level of NR2B. Florescence probe DCFH-DA kit was used to detect ROS level. TUNEL staining was used to determine apoptosis. RESULTS: When neurons were treated with 50 and 100 micromol/L MK801 to 100 micromol/L dimethoate group, Apoptosis decreased to 79.6% of 100 micromol/L dimethoate group in higher intervention group (P < 0.01). Concentration of EAA decreased in both intervention groups (P < 0.01). The level of ROS decreased to 88.9% and 74. 8% of 100 micromol/L dimethoate group (P < 0.01), while still higher than that of control group (P < 0.01). Transcription level of NR2B increased to 1.59 and 2.22 folds of 100 micromol/L dimethoate group (P < 0.01) and had big differences with control group (P < 0.01). CONCLUSION: Excitatory amino acid system and ROS both contribute to the apoptosis of neurons caused by dimethoate. MK801 not only decrease the ROS level but also diminish the elevated excitatory amino acid concentration caused by dimethoate, thus abolish apoptosis of neuron. PMID- 22043704 TI - [Effects of NF-kappaB on the expression of IL-8 in human bronchial epithelial cells induced by cigarette smoke condensates]. AB - OBJECTIVE: To investigate the effects of NF-kappaB on the expression of IL-8 in human bronchial epithelial cells induced by cigarette smoke condensates (CSC). METHODS: Both IL-8mNF-kappaB(-) BEAS-2B cells (BEAS-2B cells with mutated NF kappaB binding site in IL-8 promoter) and IL-8 WT BEAS-2B cells (wild-type BEAS 2B cells with completed NF-kappaB binding site in IL-8 promoter) were treated by 7.5% CSC. The mRNA level of fLCF gene was detected by real-time PCR, and the activity of luciferase was measured by luciferase reporter gene activity detection kit. RESULTS: After two kinds of BEAS-2B cells were treated by 7.5% CSC, the mRNA level of fLCF and the activity of luciferase in IL-8 WT BEAS-2B cells was higher than those in IL-8mNF-kappaB(-) BEAS-2B cells (P < 0.001), the mRNA level of fLCF in IL-8 WT BEAS-2B cells was 1.32 times as that in IL-8mNF kappaB(-) BEAS-2B cells (P < 0.001). CONCLUSION: The results suggested that NF kappaB transcription factor was involved in smoking-induced respiratory inflammation through the precise molecular mechanisms of promoting the release of IL-8 in BEAS-2B cells treated by CSC. PMID- 22043705 TI - [Research of chromosome aberration in Chinese hamster lung fibroblast induced by VEGF siRNA]. AB - OBJECTIVE: To explore the effects of VEGF siRNA on chromosome aberration in Chinese hamster lung fibroblasts (CHL). METHODS: The chromosome aberrations were observed after CHL were transfected with VEGF siRNA for 24 hours and 48h. RESULTS: There were a questionable positive in 100nmol/L VEGF siRNA after VEGF siRNA were transfected for 24h and the chromosome aberration rate was 6 percentages. Both 50nmol/L VEGF siRNA and 100nmol/L VEGF siRNA caused the questionable positive after VEGF siRNAs were transfected for 48h, and the chromosome aberration rates was 6 percentages and 10 percentages separately. There were no the chromosome aberration in 25nmol/L VEGF siRNA. The types of chromosomal aberration induced by VEGF siRNAs included break, Dicentric grain, polyploid, gap, and three trajectories. CONCLUSION: 100nmol/L VEGF siRNA might cause CHL chromosome aberration. PMID- 22043706 TI - [Value of oxygenic injury sensitive index in the screening of the early coal workers' pneumoconiosis]. AB - OBJECTIVE: To study the significance of oxidative injury in the screening of coal workers' pneumoconiosis (CWP). METHODS: With the method of nitrate reductase, TBA, et al, the content of NO, MDA and other indexes of peroxidation in plasma lipid were detected in 112 patients suffering from coal workers' pneumoconiosis and 114 healthy coal workers as controls. RESULTS: There were statistical significant between two groups (P < 0.05) with the content or density of MDA, CuZn-SOD, GSH-Px, T-AOC, UA, NO and iNOS except CP. As screening index of pneumoconiosis, there were statistical significant in area under the curve (AUC) of MDA, T-AOC, NO and iNOS between the two groups by ROC. As screening index of pneumoconiosis, MDA, T-AOC, NO and iNOS can be selected as early screening index. Especially, T-AOC was the best index of four indexes (sensitivity is 70.5%, specificity is 68.1%). CONCLUSION: Joint screening of MDA, T-AOC and iNOS is better than single index or series of T-AOC and MDA to the screening of CWP. PMID- 22043707 TI - [Pollution characteristics of PCBs in electronic waste dismantling areas of Zhejiang province]. AB - OBJECTIVE: To study the pollution level and distribution pattern of polychlorinated biphenyls (PCBs) in the environment media in electronic waste dismantling area of Zhejiang province. METHODS: Water, soil and PM10 were sampled in electronic waste dismantling areas. The contents, distribution characteristics and toxic equivalents (TEQs) of PCBs in local environment were evaluated by ultra trace detection methods. RESULTS: The PCBs contents of water, soil and PM10 in Luqiao and Zhenhai, the relatively high polluted areas, were higher than those in Longyou, the control area. The dominant PCBs detected from the environment in Luqiao were hexa-CBs (PCB138 and PCB153), while penta-CBs were dominant in Zhenhai and Longyou. TEQs in electronic waste recycling area were higher than those in control areas. The TEQs of PCBs in water and soil were the highest in Zhenhai, while the TEQs of PM10 were the highest in Luqiao. CONCLUSIONS: The local environment has been polluted by PCBs emitted from electronic waste recycling. PCBs pollution monitoring in electronic waste recycling area should be strengthened to prevent PCBs-induced health effects. PMID- 22043708 TI - [Effects of phytoestrogen, genistein combined with calcium and vitamin D3 on preventing osteoporosis in ovariectomized mice]. AB - OBJECTIVE: To evaluate the effects of different doses of phytoestrogen (genitein) combined with calcium and vitamin D3 on preventing osteoporosis in ovariectomized (OVX) mice. METHODS: 63 female CD-1 mice, 29g average weight, were randomly divided into 7 groups. Including Sham group, OVX group and groups of treatment with calcium, vitamin D3 and genistein in high dose (GH, 67 mg/kg), genistein in moderate does (GM, 33.5 mg/kg), genistein in low dose(GL,16.75 mg/kg), pure genistein (G) and pure 17-betaestradiol (E2). After six weeks treatment, bone mineral density (BMD), bone mineral content (BMC), Biomechanical characteristics bone strength and bone biochemical markers were measured in all mice. RESULT: In the groups of GH, GM and GL, it was stimulative effect of genistein on elevating uterine weight in ovariectomized mice and the effect in GL group is lower. BMD, BMC, length and width of femora were significantly increased in GM group mice than those in OVX mice (P < 0.01), as well as BMD of femora in GL group mice were markedly increased (P < 0.01). Peak load and resilience of femora were the most conspicuously increased in GL group mice than those in others treatment group mice (P < 0.01). In GL group, bone alkaline phosphatase (BALP) increased and tartrate-resistant acid phosphatase (TRAP) decreased (P < 0.01). CONCLUSION: It was lower stimulative effect of low dose of phytoestrogen (genitein) combined with calcium and vitamin D3 on elevating uterine weight in ovariectomized mice. Low dose of Phytoestrogen (genistein) combined with calcium and vitamin D3 might increase BMD, improve the mechanical strength of bone, promote bone fromation and inhibit bone resorption significantly. It might reduce the dose of genistein administrated and be safter than E2. PMID- 22043709 TI - [Serum carotenoid concentrations in some Chinese adults from urban, suburban and rural communities]. AB - OBJECTIVE: The study was carried out to analyze serum carotenoids concentration of some Chinese adults by HPLC. METHODS: One hundred and eighty four 30 - 60 year old adults (84 males and 100 females) from three different communities were recruited in the investigation. The fast blood samples were collected and separated into serum in summer, autumn, winter and spring of the year, respectively. The serum were extracted with organic solvents and analyzed with a HP1100 HPLC for the concentration of beta-carotene, alpha-carotene, beta cryptoxanthin, lycopene, and lutein/zeaxanthin. RESULTS: The average serum concentration of carotenoids of investigated population in summer, autumn, winter and spring were as followed (inmicromol/L), respectively: beta-carotene, 0.72 +/- 0.20, 0.71 +/- 0.18, 0.70 +/- 0.19 and 0.63 +/- 0.20; alpha-carotene, 0.037 +/- 0.018, 0.039 +/- 0.015, 0.038 +/- 0.017 and 0.030 +/- 0.019; beta-cryptoxanthin, 0.11 +/- 0.03, 0.14 +/- 0.03, 0.13 +/- 0.04 and 0.10 +/- 0.03; lutein + zeaxanthin, 0.61 +/- 0.16, 0.45 +/- 0.09, 0.46 +/- 0.12 and 0.47 +/- 0.14; lycopene, 0.43 +/- 0.26, 0.11 +/- 0.06, 0.07 +/- 0. 04 and 0.07 +/- 0.03. The average serum beta-carotene concentration of total-population was lowest in spring, but the descent did not occurred from urban sub-population. There were significant seasonal changes in average serum concentrations of alpha-carotene, beta-cryptoxanthin, lutein + zeaxanthin, and lycopene from total population. Further more, there was significant difference of serum concentration of every carotenoid between three sub-populations in every season. CONCLUSIONS: The data of serum carotenoid concentration in total 713 blood samples from some Chinese adults were reported here, which would be helpful to understanding the population distribution of carotenoid concentration in China. PMID- 22043710 TI - [Relative validity of food frequency questionnaire for estimating dietary iron intake of students with anemia]. AB - OBJECTIVE: To assess the relative validity of food frequency questionnaire (FFQ) for estimating dietary iron and its related nutrients and food intakes of students with anemia. METHODS: FFQ and weighed dietary records combining with 24h dietary recalls (adopted as reference method) were applied respectively to investigate the diet of 156 anemic students aged 10 - 12 years. The average dietary intakes of iron, haem iron, non-haem iron, vitamin C, meat/fish/poultry and eggs were estimated. Wilcoxon matched-pairs signed-rank test, Spearman's rank correlation, cross-classification and actual values for surrogate categories were performed to assess the relative validity of FFQ. RESULTS: Compared with the reference method, dietary iron and its related nutrients and food intakes were overestimated by FFQ, and bear poor correlation with reference method. The results of cross-classification and actual values for surrogate categories indicated that the low and high intakes of all dietary components could not be clearly differentiated by FFQ. CONCLUSION: FFQ presents unsatisfactory accuracy in assessing dietary intakes of iron and related nutrients of anemic students in less developed districts. PMID- 22043711 TI - [Effect of dietary protein on serum lipid profile in hypercholesterolemic people]. AB - OBJECTIVE: To observe the effect of soy protein on the concentration of serum lipids in hypercholesterolemic people and the correlation between dietary protein and serum lipids. METHODS: Ninety healthy hypercholesterolemic volunteers were given beverages contained either 24 g of casein or 18 g of soy protein plus 6 g of casein by random daily for 8 weeks without change of their habitual life. Body height, body weight, waist and hip circumference and serum lipids were measured before and after the study. RESULT: (1) The body weight and body mass index of subjects in the soy group were decreased slightly but significantly (P < 0.05), while the waist-to-hip circumference of subjects in casein group was decreased (P < 0.05). (2) ApoB and TC/HDL-C ratio were significantly reduced after consuming soy protein beverages for 8 weeks (P < 0.05), while in casein group, TC, LDL-C and ApoB were reduced significantly (P < 0.05). (3) The reduction in TC concentration was negatively correlated with the quantity of dietary protein intake (r = - 0.419, P < 0.01), whereas it was positively correlated with the quantity of vegetable protein intake (r = 0.521, P < 0.01). CONCLUSION: The effect of soy protein on serum lipids could be influenced by the source and quantity of dietary protein. PMID- 22043712 TI - [Occurrence of synthetic musks in human milk samples collected from Beijing]. AB - OBJECTIVE: To investigate the occurrence of 13 kinds of synthetic musk and triclosan in breast milk samples collected from Beijing, and to estimate the exposure of breastfed infants. METHODS: Target compounds in 65 milk samples collected from 4 districts of Beijing in 2004 were analyzed by means of gas chromatography - tandem mass spectrometry (GC - MS/MS) and quantified by internal standards. The exposure of infants was analyzed statistically by SPSS software. RESULTS: HHCB, AHTN, OTNE, MT and Triclosan were detected in milk samples in the range of 0.6 - 174.1 ng/g lipid, with some difference in 4 districts. It is estimated that the intake of synthetic musks and triclosan for each infant from breast milk would be 13.5 - 3917 ng/d. CONCLUSION: Commonly used synthetic musks and tricloson were generally detected in breast milk. Further study should be focused on monitoring and tracing the possible source of pollution. PMID- 22043713 TI - [Analysis on the quality of life of people born in famine years (1959 -1961) in Chongqing city and its influencing factors]. AB - OBJECTIVE: To investigate the current quality of life of people born in famine years (1959 - 1961) in Chongqing and its influencing factors. METHODS: A total of 1140 people were selected from five districts or counties of Chongqing by a multi stage stratified random sampling method. People born in 1957 - 1959 were set to group G1, 1957 -1962 to group G2, and 1960 -1965 to group G3. The second edition of SF-36 Health Survey and a general situation questionnaire were used for the investigation. The quality of life was evaluated on 8 dimensions and quantified by scoring. RESULTS: Among the 8 dimensions of the quality of life, the scores of role-physical (RP), role-emotional (RE) and physical function (PF) of people in group G1 who experienced famine in fetal period were 84.26 (17.09, 84.57 (16 48 and 87.57 (15.84 respectively, which was significantly lower than the scores of people in group G3 who have never experienced famine (P < 0.05); the physical function (PF) score of people group G2 who experienced hunger in infants and young children period was 87.65 (15.03, which was significantly less than the population in group G3 (P < 0.05), while the vitality (VT) score of group G2 was 48.26 (9.34, significantly higher than the population in group G3 (P < 0.05). The average monthly income, appetite, life satisfaction are the main factors influencing the quality of life of people in group G1. The life satisfaction, appetite and the situation getting along with other family members are the main factors influencing the quality of life of all target population (???). DISCUSSION: Strengthening prenatal nutrition has certain influences on improving the quality of life in adulthood. However, developing a positive attitude towards life, a good appetite and harmonious family relationships are much more important for improving the life quality of all population. PMID- 22043714 TI - [Whey protein improves insulin resistance via the increase of antioxidant capacity in model rats]. AB - OBJECTIVE: To investigate the effects of whey protein on insulin resistance in model rats. METHODS: Insulin resistance model rats were established by feeding high-fat diet in Wistar rats. Model rats were then randomly divided into 4 groups of 10 animals each and fed on 0% whey protein (WP), 5% WP and 15% WP. After 8 weeks, fasting blood glucose (FBG), fasting plasma insulin (FINS) were determined. Oral glucose tolerance test (OGTT) was performed and glucose area under the curve (AUC) was calculated. Also, plasma total anti-oxidation capacity (T-AOC), superoxide dismutase (SOD), reduced glutathione hormone (GSH) and malondialdehyde (MDA) were determined. RESULTS: Whey protein intake did not affected FBG and glucose AUC. FINS and homeostatic model assessment-insulin resistance (HOMA-IR) were significantly lower in 15% WP group than in 0% WP group. For antioxidant index,plasma level of T-AOC, SOD and GSH were significantly higher in 15% WP group than in 0% WP group (T-AOC : P < 0.01; SOD, GSH : P < 0.05); however, MDA was significantly lower in 15% WP group than in 0% WP group (P < 0.05). CONCLUSION: Whey protein improves insulin resistance. This effect is related to the increase of antioxidant capacity in insulin resistance model rats. PMID- 22043715 TI - [Effects of lycopene on blood cells and fibrinolytic activity in hyperlipidemic rats]. AB - OBJECTIVE: To explore the effects of lycopene on blood cells and fibrinolytic activity in hyperlipidemic rats. METHODS: Forty adult male SD rats were divided randomly into five groups: normal control group, high fat model group, fluvastatin sodium group, lycopene low-dose group and lycopene high-dose group based on the level of serum TC. Normal control group was fed with normal animal diet, other groups were fed with high fat diet. Fluvastatin sodium and lycopene were given by intragastric administration in the last two weeks of experiment. The level of serum lipid, SOD, MDA, blood cell parameters, platelet (granule membrane protein (GMP-140), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured. The pathological changes of aorta were observed and atherosclerosis index was calculated. RESULTS: Hyperlipidemia was induced in rats after feeding high fat diet for one week. In comparison with high fat diet model group, serum TC, TG, LDL-C and MDA were decreased but HDL-C and SOD were increased in lycopene groups. White blood cell count, mean volume of red blood cells and platelets, GMP-140 and PAI-1 were decreased, but red blood cell count and tPA were increased; atherosclerosis index were decreased, foam cells were decreased in intima, pathological changes in aorta were reduced in lycopene groups. The effects were obvious in lycopene 44 mg/kg bw group. CONCLUSION: The effect of lycopene on protecting blood cell, promoting fibrinolytic activity and reducing aortic lesions in hyperlipidemic rats might be the result of reducing blood lipids and improving antioxidation. PMID- 22043716 TI - [Hydrolysis method for whey protein and the hypoglycemic activity of its peptides in diabetic KKAy mice]. AB - OBJECTIVE: To explore the hydrolysis method for whey protein with alkaline proteinase, and to investigate the hypoglycemic activity of the peptides in diabetic KKAy mice. METHODS: Whey protein was hydrolyzed with alkaline proteinase, and the degree of hydrolysis, nitrogen and amino acid content, mass spectrographic analysis of the peptides were determined. Changes of fasting blood glucose, random blood glucose, glucose tolerance and insulin levels in diabetic KKAy mice were measured after the peptides were given by gavage. RESULTS: The degree of hydrolysis of whey protein was 14.8%, the nitrogen in the peptides was 68.2%, and the molecular weight of the peptides was 900 - 1900 Dal, mostly was 1800 - 1900 Dal. Blood glucose of KKAy mice was decreased at 0.5 and 1 h after oral injection of the peptides, and insulin level was increased at 0.5 h after ingestion of the peptides. CONCLUSION: Fasting blood glucose and random blood glucose levels of type 2 diabetic KKAy mice could be significantly decreased, and the glucose tolerance and insulin secretion of mice could be improved by whey protein peptides. PMID- 22043717 TI - [Cloning and sequencing full-length genome of H5N1 avian influenza A virus and molecular evolution analysis of HA gene]. AB - OBJECTIVE: To clone and sequence full-length genome of the avian influenza A/Chicken/Hubei/489/ 2004(H5N1) virus, in order to analyze genetic mutation patterns of HA gene and polygenetic relationship between A/Chicken/Hubei/489/2004 (H5N1) virus and other strains since 1996. METHODS: 8 genes of the avian influenza A/Chicken/Hubei/489/2004 (H5N1) virus were amplified and cloned, and then genetic mutation analysis and phylogenetic trees were made by bioinformatics software. RESULTS: Full-length genome of the avian influenza A/Chicken/Hubei/489/2004 (H5N1) virus were cloned into the vector of PMD18-T. Genetic evolution analysis showed that there is a specific cleavage site of "PQRERRRKKR", which was proved be related with virulence. In addition, molecular phylogenetic trees of HA gene revealed that A/Chicken/Hubei/ 489/2004 virus were closely related to H5N1 viruses of 2000-2006 isolated in Hong Kong and in Southeast Asia. CONCLUSION: The influenza A/Chicken/Hubei/489/2004 (H5N1) virus was closest genetic relatives to the influenza A/Chicken/HongKong/YU777/2002 (H5N1) virus, and it was most possible that the avian influenza outbreak was caused by the 2002 lineage of Hong Kong. PMID- 22043718 TI - [Detection for respiratory viruses in Shanghai with multiplex PCR from 2009 to 2010]. AB - OBJECTIVE: To characterize the prevalence and occurrence of respiratory viruses in children in Shanghai China. METHODS: Respiratory virus were identified from aspirates and throat swabs selected from children with respiratory symptom who visited the Shanghai Children Hospital during period January 2009 to March 2010. Respiratory virus was detected by multiplex PCR. RESULTS: Virus were detected in 301 patients (58%), among them. RSVB infection were the most frequent 37.5% of 301 patients. HRV A/B was found in 17.3% (52 patients). Adv and PIV3 in 9% (27 patients) HMPV in 6% (18 patients). CONCLUSION: The data indicate that RSVB HRV A/B and PIV3 Adv is an important etiological agent for respiratory infection in children during the survey period. HRV A/B combined other virus are the most virus for combined infection. PMID- 22043719 TI - [Maternal sulfur dioxide exposure and the risk of low birth-weight babies]. AB - The relationship between maternal exposure to sulfur dioxide (SO2) and the risk of low birth-weight (LBW) babies which has been reported in literatures remained inconclusive. In this study, the data on SO2 emission, meteorology, topography as well as LBW and control babies in the Dallas-Fort Worth area of the United States in 1997 were collected to re-examine the associations between maternal SO2 exposure and the risk of LBW in babies. A combination of air dispersion modeling, Geographic Information System (GIS) spatial interpolation and geo-statistical analysis, as well as logistic regression was used for analyses. Results showed that the risk of LBW was not significantly increased with the exposure of pregnant mothers to higher level of SO2 when all data were considered together as one group. However, for mothers at the age 35 or older, the risk of LBW babies was higher in exposure to SO2 (OR = 2.31, 95% CI 1.01 - 5.30). Therefore, the potential risk of LBW baby might be higher in elder women in exposure to SO2 during pregnancy. PMID- 22043720 TI - [Systematic review of public literatures on HIV-1 genetic subtype in China]. AB - OBJECTIVE: To identify the characteristics of HIV-1 and their distributions in the different infective subject of China, and provide base data for prevention and treatment of HIV infection. METHODS: We searched electronic databases such as the Chinese National Knowledge Infrastructure (CNKI), the Wanfang database and the Chinese Science and Technology Journal Full-text Database (VIP). Analysis the distributions of HIV subtype according the data acquired. RESULTS: A total of 62 articles were included with a total of 2091 cases reported. The main subtype epidemic in our country were B(12.4%), B(23.9%), CRF01-AE(30.0%) and CRF BC(27.2%). There was relationship between the subtypes and the transmission routines. The circulation recombinant forms increased recently in our country. CONCLUSION: The epidemic of HIV subtype in our country was more complicated, and gave more perplex in surveillance, prevention and treatment, meanwhile, it also gave more challenge for the vaccinal manufacture. PMID- 22043721 TI - Managed care considerations. A new era of advanced prostate cancer management. PMID- 22043722 TI - A place to call home. Assisted living providers focus on specialty care. PMID- 22043723 TI - Nurse retention review. PMID- 22043724 TI - Hearts full of grace. PMID- 22043725 TI - Difficult behaviors decoded. PMID- 22043726 TI - Superstars: to hire or Not to hire? PMID- 22043727 TI - CTAs revisited. AB - It is important that you ensure you are billing correctly for CT/CTA studies based on what is documented. From a facility perspective, you may know that a CTA study is being performed, but if it is not adequately documented you may have a refund obligation in the event of a payor audit. This is a key issue that I recommend all organizations, regardless of which side you are billing, review to ensure compliance. PMID- 22043728 TI - ICD-10: diagnostic mammograms. PMID- 22043729 TI - Revisit, revamp and revitalize your business plan: Part 4. AB - A best practice for all imaging leaders working on a management development program should be to invest enough time to complete a detailed planthatsetsgoals, objectives, step targets, landmarks, and a timetable for their achievements. Keys to success for a management development program include no surprises, active participation, and preparation by both the facilitator and the managers involved. A successful management team will have trained staff and lean processes mapped and documented, as well as be comfortable in a coaching, delegating, and consensus management style. PMID- 22043730 TI - Full circle. PMID- 22043732 TI - There's an app for that! PMID- 22043731 TI - Magnetic fields of green. AB - By incorporating even the basic elements of a more environmentally friendly, "green"construction and design in an MRI setting can create a safer, more pleasant space for the patients and staff, better images, and operational cost savings. Using building systems that have reduced amounts of steel can decrease construction time, increase thermal insulation, and reduce the weight of the structure meaning less energy required to transport and install. HVAC systems and lighting design can also play a major role in creating a "green"MRI suite. LEED certification places a focus on quality of the built environment, life cycle cost, and a productive indoor environment, as well as impact on the exterior environment. An LEED certified building considers costs and benefits for the lifetime of the building. PMID- 22043733 TI - Improving satisfaction performance through faster turnaround times. AB - In order to increase satisfaction and improve department performance, Florida Hospital Memorial Medical Center focused on decreasing report turnaround time with a goal of two hours from completion of the examination by the technologist to a final signed report by the radiologist. Through the introduction of voice recognition software, not only were efficiencies gained, but there was a dramatic reduction in transcription costs--from $30,000 per month to less than $300. Turnaround times were ultimately reduced, thus improving performance and increasing satisfaction. This was made evident by the tracking over time of physician satisfaction scores and HCAHPS scores rating patient satisfaction. PMID- 22043734 TI - Advanced computed tomography technology and patient dose: a literature review. AB - Cumulative patient radiation dose is a hot topic making headlines today. Responsible for almost two thirds of the medical radiation dose given to patients, computed tomography (CT) has been the major target of these news articles. Through this review of peer reviewed publications, an examination of the relationship between the advancement of technology in CT equipment and the increasing patient dose areexplored. Discussion includes CT scan protocols, demands of physicians, equipment capabilities, and possible solutions to address the problem. Although most of these issues are well known in the imaging community, a few of the results are somewhat surprising. The information disclosed will help form a path to a future with lowerradiation doses received by all patients. PMID- 22043735 TI - A culture of extraordinary care: Part 4. PMID- 22043736 TI - Graduation. PMID- 22043737 TI - Staying on your your feet. AB - CIOs are hard at work coming up with the most effective and affordable strategies for protecting electronic data as their hospitals move forward on electronic medical records. While the rise of cloud computing and declining network costs are offering new opportunities in dealing with potential disasters, many find there is no substitute for good planning and constant testing. PMID- 22043738 TI - Infrastructure for improvement. AB - The fact that many clinical performance measures are now being designed with EHRs as their data source may lead to systemic improvements in patient safety. Healthcare Informatics looks at four healthcare providers whose IT infrastructures already underpin their performance improvement strategies. PMID- 22043739 TI - Ambulatory EHR and practice management system demand. PMID- 22043740 TI - What HIXs can learn from HIEs. PMID- 22043741 TI - Ambulatory information systems: the last frontier. PMID- 22043742 TI - Why would I want to work for you? PMID- 22043743 TI - Pediatric magnetic resonance research and the minimal-risk standard. PMID- 22043744 TI - Misunderstanding, period. PMID- 22043745 TI - The merits of procedure-level risk-benefit assessment. PMID- 22043746 TI - Researcher experiences with IRBs: a survey of members of the American College of Neuropsychopharmacology. PMID- 22043747 TI - Latex allergy in dental students: a cross-sectional study. AB - BACKGROUND: Latex allergy is a major occupational health problem in health care workers who regularly use latex gloves. Dentists are one of the high risk groups for latex allergy and sensitization as it is generally found that healthcare workers (HCW) have 3 times greater prevalence of latex allergy. There are very few studies of latex allergy in HCW in Thailand. OBJECTIVE: To study the prevalence of latex-related symptoms, latex-sensitization and possible risk factors in dental students. MATERIAL AND METHOD: A cross-sectional study was performed on all dental students of the Faculty of Dentistry, Chulalongkorn University, during Dec 2007 to May 2008, using questionnaires and skin prick tests (SPT), using 3 latex extracts prepared from Proglove, Doctor Plus gloves and a commercial latex allergen (Stallergenes, France). SPT was done only in those who were willing and signed informed consents. RESULTS: There were 617 completed questionnaires (87.3%). The mean age of the volunteers was 20.9 +/- 1.7 years with 29.3% male and 70.7% female. The prevalence of latex glove-related symptoms was 5.0%. These symptoms were all local, cutaneous symptoms, ranging from hand pruritus (64.5%), hand eczema (19.4%) and contact urticaria (16.1%). Eight subjects (1.3%) reported pruritus or urticaria on exposure to other rubber products while 12 subjects (1.9%) reported reactions to some fruits. The risk factors for latex-glove allergy were personal history of allergic diseases (atopic dermatitis, urticaria, pruritus and rubber allergy), duration of using gloves more than 18 hours per week, more than 3 pairs of gloves used per day and timing of glove exposure. The 4th to 6th year students were observed significantly more prevalence of symptoms than the 1st to 3rd year students (OR, 3.69; 95% CI, 1.73-7.87; p = 0.0003). SPT for 3 extracts of latex was done in 247 cases (40.0%); overall latex sensitization rate was 14.2%. The commercial extract had higher incidence of latex sensitization compared to the 2 gloves extract. The 1st year students had the lowest percentage of latex sensitization (3.2%) and positive skin test was significantly found in the 2nd year students (20.8%; OR, 6.46; 95% CI, 1.87-47.98; p = 0.04). CONCLUSION: The prevalence of latex allergy in dental students is 5% and the signs and symptoms were local cutaneous reaction; pruritus, eczema and contact urticaria. The latex sensitization rate in dental students was14.2%, which is higher than the general population. The possible risk factors included personal history of allergic diseases, duration and frequency of exposure. Therefore, primary prevention of the occupational latex allergy should be carefully considered especially concerning high risk factors. PMID- 22043748 TI - Effects of temperature and time delay on arterial blood gas and electrolyte measurements. AB - OBJECTIVE: To determine the changes in pH, PaO2, PaCO2 and Na, K, Cl in arterial blood samples stored at room temperature or on ice, at 0, 15, 30, 45 and 60 minutes. MATERIAL AND METHOD: Arterial blood samples were collected in heparinized capillary tubes and stored at room temperature (24-26 degrees C) and on ice (0-4 degrees C). ABG and electrolytes were measured at 0, 15, 30, 45 and 60 minute intervals. RESULTS: There were significant decreases in the pH, PaO2, Na, Cl and significant increases in PaCO2 and K over time in both groups. The changes were greater and faster at room temperature. The significant decrease in pH over time was not found until 30 minutes at room temperature and 45 minutes on ice. There were significant decreases in PaO2, concurrent with significant increases in PaCO2 from 15 minutes onwards in both groups. Both Na and K exhibited a significant change at 60 minutes in the room temperature group. Significant decreases of Cl over time were not found until 15 minutes at room temperature, and 30 minutes on ice. CONCLUSION: For ABG and electrolytes analysis, the blood sample should be analyzed within 15 minutes and be stored at either room temperature or on ice. PMID- 22043749 TI - Combine intravitreal bevacizumab injection with laser treatment for aggressive posterior retinopathy of prematurity (AP-ROP). AB - OBJECTIVE: To assess a new method the "Combine Treatment" consisted of diode laser photocoagulation and intravitreal bevacizumab for treatment of AP-ROP. MATERIAL AND METHOD: These retrospective and non-comparative case series study in twelve premature infants (7 Male, 5 Female) from ROP clinic with diagnosis of aggressive posterior retinopathy of prematurity (AP-ROP) based on indirect ophthalmoscopic examination were included in the present study. The "Combine Treatment" consisted of one treatment session in which diode laser photocoagulation was applied in the avascular zone (anterior and posterior to the presumed ridge include vascular nets up to the clear retina) followed by intravitreal injection of Bevacizumab (Avastin). Fundus photographs were obtained before and after the treatment using a wide-field digital pediatric imaging system (RetCam). RESULTS: Twenty-three eyes were treated with the "Combine Treatment". The rest were treated with only laser abrasion. All patients got favorable anatomical outcomes of all treated eyes. Proliferative tissue started regress 2 weeks after treatment and completed regress about 4.92 weeks (range; 3 7 weeks). There was neither progression of disease nor serious ocular or systemic complications. No further treatments were needed. CONCLUSION: In the present study, one session of the "Combine Treatment" leads to favorable anatomical outcomes for patients with AP-ROP. This new approach prevents aggressive progression and offers hope of good future vision to patients. The authors hope that this new approach will be another choice of treatment to prevent aggressive progression of the disease and gain good vision in the future. PMID- 22043750 TI - Result of air enema reduction in 737 cases of intussusception. AB - OBJECTIVE: To show the success of air enema reduction for intussusception at Queen Sirikit National Institute of Child Health, a tertiary center for children in Bangkok, Thailand. MATERIAL AND METHOD: Medical records of patients treated for intussusception by air enema reduction between 1992 and 2009 were reviewed for the success rate. RESULTS: The treatment for intussusception at Queen Sirikit National Institute of Child Health was changed from barium enema to air enema reduction since 1992. And was the first institute in Thailand that performed air enema reduction by modified the instrument from blood pressure device. The result of success rate was 68% from the total of intussusception 737 cases with successful reduction of 498 cases. The pressure was not more than 120 mmHg. There was bowel perforation in 4 cases (0.5%) but no death occurred. CONCLUSION: The success rate is not as high as other countries because of late presentation with small bowel obstruction. However, air enema reduction is a safe method and is the first method of choice before surgery. Early diagnosis and early treatment help the patient from surgery. PMID- 22043751 TI - Comparison outcomes of sick babies born to teenage mothers with those born to adult mothers. AB - BACKGROUND: Adolescent period is the transitional stage of physical and mental development from childhood to adulthood. Pregnancy in teenage girls is generally classified to have a higher risk than those in adults. In many previous studies reported only the outcome of teenage mothers but no comparative outcome between sick babies born to teen mothers and adult mothers, so the authors conducted the present study. OBJECTIVE: To compare the outcomes of sick infants born to teenage mothers with those born to adult mothers (age > or = 20 years). MATERIAL AND METHOD: This prospective study was carried out from October 1st, 2006 to September 30th, 2009. The study group consisted of sick babies born to teenage mothers and admitted at Queen Sirikit National Institute of Child Health (QSNICH). These babies were compared to sick babies (control group) born to adult mothers during the same period. The demographic data of mothers and sick babies in both groups were recorded in the designed case record forms. Developmental assessment was done until two years of age. RESULTS: A total of 6,342 deliveries took place in Rajavithi Hospital during the study period of which 697 babies were born to teenage mothers. The incidence of teenage pregnancy was 10.99%. The number of sick babies from teenage mothers and adult mothers were 78 and 147 cases, respectively. There was a significantly higher mortality in the study group (7 cases, 9%) than the control group (4 cases, 2.7%). There was statistically significant difference in most of the demographic characteristics between the teenage and adult mothers except anemia, PROM and MSAF (meconium stain amniotic fluid). Although there was a trend of more cases of anemia and MSAF in teenage mothers than in adult mothers, there was no statistically significant difference. There was a shorter interval time from marriage to pregnancy in teen mothers than in adult mothers and a lower number of antenatal care visits with late antenatal care among the teenage mothers too. On comparing the data in infants, the teenage group had more males and a higher blood pressure than those in the adult group. There were significantly more preterm infants and higher cesarean section in the adult group too. Gastroschisis cases were found only in the teenage group. In follow-up cases, more than seventy percent in both groups were assessed for developmental outcome until two years of age. Divorce was found in teen mothers more than in adult mothers (17.54 vs. 3%) and more cases in teenage infants received care in rural areas by grandparents (36.6 vs. 12.6%). Delayed speech was found in more cases in the teen group than in the adult group (12.28 vs. 6%). CONCLUSION: The number of antenatal care in teenage mothers was less than in standard pregnancy care. Cesarean section rate was lower in teenage mothers than in the adult mothers. Preterm infants were found in more cases in the adult group but gastroschisis was found only in the teenage group. More cases of infants in the teenage group received care in rural areas by grandparents and divorce occurred more in teen mothers than adult mothers. PMID- 22043752 TI - Compare severity of bronchopulmonary dysplasia in neonates with respiratory distress syndrome treated with surfactant to without surfactant. AB - BACKGROUND: The utilization of surfactant replacement therapy had been limited in treatment of respiratory distress syndrome (RDS) due to the high cost especially in developing countries. Nowadays, the National Health Insurance Policy has covered the cost of surfactant for the patients. Therefore, bronchopulmonary dysplasia (BPD) may be found increasing due to increased survival in patients with severe RDS. OBJECTIVE: To compare immediate treatment outcome of severity of BPD and outcome after hospital discharge in neonates with RDS who were treated with or without surfactant. STUDY DESIGN: Retrospective cohort study. MATERIAL AND METHOD: The data of 54 infants who developed BPD after RDS at Queen Sirikit National Institute of Child Health between January 1st, 2003 and December 31th, 2005 were kept in database format. The database was analyzed for difference between groups and the outcome of immediate treatment, severity of BPD and outcome after hospital discharge were compared. The study group was BPD cases from RDS treated with surfactant compared to control (BPD cases from RDS treated without surfactant) groups. RESULTS: Forty-three (80%) from fifty-four cases had completed data and were included into the present study. There was no statistically significant difference in maternal conditions and neonatal conditions between groups. Antenatal steroid was prescribed more often in RDS without surfactant group than surfactant group. The mean birth weight and gestational age in surfactant and without surfactant groups were 1,179.1 +/- 274.3 gm vs. 1,114.4 +/- 338.3 gm and 29 +/- 1.6 weeks vs. 29.2 +/- 2.7 weeks respectively, but no significant differences were observed between groups. To compare the severity of RDS, only 17.6% of moderate to severe RDS in the control group was found, whereas 100% was found in the study group. Moderate to severe BPD cases were found more often in the control group (70.6%) than in the study group (61.6%), but no statistically significant difference was shown. The immediate complications, e.g. pneumothorax (5.9%) and pneumomediastinum (5.9%) were found in the control group, but pulmonary hemorrhage occurred more often in the study group than the control group (11.5% vs. 5.9%). For long-term follow-up, the development outcome was not different between groups. CONCLUSION: The present study revealed no statistically significant difference in severity of BPD in neonates with RDS treated with and without surfactant groups. In addition, surfactant was useful in moderate to severe RDS because no early complication such as air leak syndrome was found in this group. PMID- 22043753 TI - Eosinophilic gastrointestinal disease: analysis of sixteen cases from ten years experience in Thailand. AB - OBJECTIVE: To study eosinophilic gastrointestinal disease (EGIDs) in children concerning the clinical presentations, diagnostic methods and results of treatment. MATERIAL AND METHOD: A retrospective study of EGIDs was done from January 2000 to December 2009. All patients diagnosed as EGIDs according to gastrointestinal symptoms combined with eosinophilic infiltration in mucosal, muscular or serosal layer of involvement. Exclusion of extraintestinal eosinophilic involvement and parasitic infestations were done. Analysis of clinical presentations, diagnostic methods and results of treatment were reviewed. RESULTS: Sixteen children fulfilled criteria of EGIDs. Mucosal type was the most common finding type (12 out of 16 cases) (75%). Muscular and serosal type was found in equal numbers (2 of each in 16 cases) (12.5% each). Ages ranged from 6 months to 13 years. The male: female ratio was 1: 1.2. Abdominal pain was the most common presenting symptom followed by diarrhea. Allergic history was detected in 68.75% of all patients. Peripheral eosinophilia was found in only 37.5% of all cases. Radiographic findings showed non-specific findings. Endoscopy was performed in 14 out of 16 cases (87.5%). Lymphoid hyperplasia was the most common endoscopic finding especially in mucosal type. Eosinophil (more than 20 per high power field) was found from biopsied tissues obtained from the esophagus, stomach, colon or from ascitic fluid. Prednisolone was used in 13 out of 16 cases with satisfactory results in 11 cases. The two resisted cases responded to ketotifen in one and the other in combination with montelukast. One out of 16 cases subsided with only proton pump inhibitor The last two cases improved by allergic food elimination. CONCLUSION: Eosinophilic gastrointestinal disease in children presents with varieties of gastrointestinal symptoms. Biopsied tissues or ascitic fluid are required to demonstrate significant eosinophilic infiltration or presence of eosinophil. Allergic history seems to play an important role in more than half of the patients. Specific dietary elimination is the most important treatment in allergic cases. Corticosteroid is the treatment of choice in the non-allergic group or for those who did not improve with food elimination. PMID- 22043754 TI - Clinical outcome of patients with gastroschisis: what are the differences from the past? AB - OBJECTIVE: The aim of the present study was to review the experience in management of neonates with gastroschisis and analyze the differences in the clinical outcome during a 24-year period. MATERIAL AND METHOD: A retrospective study of patients with gastroschisis treated at Queen Sirikit National Institute of Child Health (QSNICH) between 1986 and 2009 was conducted. Patients' information was compared between the first period (1986-1997) and the second period (1998-2009) regarding demographic data, modes of operative procedures and results of the treatment. The statistical differences were analyzed by the Chi square, Fisher exact and student t-test with a p-value less than 0.05 considered significant. RESULTS: During a 24-year period, 919 neonates with gastroschisis were treated at QSNICH; 342 cases (161 males and 181 females) in the first 12 year period and 577 cases (295 males and 282 females) in the second 12-year period. The incidence of gastroschisis at Rajavithi Hospital was 0.26: 1,000 live births in the first period and 1.03: 1,000 live births in the second period. Average birth weight of the patients and average maternal age in both periods were not significantly different (p > 0.05). Congenital anomalies were found in approximately 15% of the patients in each period. Regarding modes of the operative treatment, primary closure of the abdominal wall defect was attempted in 23.7% of the patients during the first period and increased to 44% in the second period. The overall survival rate in the second period was better than the first period with statistical significance (92.4% vs. 75.4%, p < 0.001). In addition, complications in the second period were less than those in the first period, except for necrotizing enterocolitis, which was more frequent in the second period. CONCLUSION: The obvious differences in patients with gastroschisis during the 24-year period were the increased incidence, increased successful primary closure of the abdominal wall defect and increased overall survival rate between 1998-2009. Improvement of the clinical outcomes reflected improved neonatal care including surgical techniques, parenteral nutrition, respiratory care and anesthetic practice. PMID- 22043755 TI - Dengue shock syndrome at the emergency room of Queen Sirikit National Institute of Child Health, Bangkok, Thailand. AB - BACKGROUND: Dengue virus infection is an important mosquito-borne disease with the reported 40,000-100,000 cases per year in Thailand. Shock is one of the common presentations at the emergency room (ER) and dengue shock syndrome (DSS) is among the common causes of shock. Proper and timely management of DSS determines the outcomes and prognosis of DSS patients. OBJECTIVE: To find the prevalence of DSS at the ER and evaluate the medical management and risk factors associated with the outcome of DSS patients. MATERIAL AND METHOD: A retrospective study on patients who presented with shock, including DSS patients at the ER of Queen Sirikit National Institute of Child Health (QSNICH), Bangkok, Thailand, from 1st January 2008 to 31st December 2009 was done. The prevalence of patients who presented with shock at the ER was retrieved from the Statistical and Information Technology Departments. Out-patient cards and In-patient charts of DSS patients were reviewed. Clinical and laboratory data were compared between recovered and death cases. Statistical analysis was done by using SPSS version 14.0. RESULTS: There were 109 shock patients seen at the ER during the present study period with 59 DSS (54.1%), 30 septic shock (27.5%), 13 hypovolemic shock (11.9%), 1 cardiogenic shock (0.9%) and 6 other non-specific shock (5.5%). DSS cases were found all year round with the peak prevalence from June to August which is the rainy season. Twenty-six of DSS (44.1%) were referred cases and 5 of them died, case fatality rate was 8.8%. All death cases had prolonged shock, massive bleeding and liver failure at presentation while these findings were found in 2 (4.4%), 16 (35.6%) and 10 (22.2%) cases of recovered cases. Encephalopathy, renal failure and respiratory failure were found in 80, 60 and 60% of the death cases while in recovered cases they were found in 11.1, 4.4 and 2.2%. Acidosis was found higher in the death group (60%) than in recovered group (8.9%). Other common presenting findings in death and recovered groups were bleeding (35.6 vs 100.0%), fluid over load (31.1 vs. 80%), hyponatremia (40% for both groups) and hypocalcemia (83.3 vs. 80%). Among the 45 recovered cases; 3 cases were misdiagnosed and another 8 cases (17.8%) received no i.v. fluid at the ER. Cross matching was done in 32 cases (64%) and blood was transfused in 16 cases (50% of the cross matching). CONCLUSION: DSS is the most common shock found at the ER especially during June to August. ER physicians should be alert for making the correct diagnosis of DSS with proper intravenous fluid resuscitation and correction of the common complications/laboratory abnormalities, i.e. acidosis, hyponatremia, hypocalcemia and cross matching for massive bleeding. A referred case with liver failure together with renal and respiratory failure was likely associated with mortality while fluid overload and significant bleeding do not if they are managed properly. Early signs of shock should be detected in walk in cases to prevent later shock after admission. PMID- 22043756 TI - Outcome of oral sildenafil therapy on persistent pulmonary hypertension of the newborn at Queen Sirikit National Institute of Child Health. AB - BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a common problem in the neonates with a high mortality rate. The prevalence ranges from 0.38-0.99 per 1,000 live births at Queen Sirikit National Institute of Child Health. The survival rate has improved after the advent of high-frequency ventilation and inhaled nitric oxide. However, inhaled nitric oxide is expensive and unavailable in most neonatal centers in Thailand. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance and hence may play a role in the treatment of PPHN. OBJECTIVE: To evaluate effectiveness and short-term side effects of oral sildenafil for infants > 36 weeks gestational age who have PPHN. MATERIAL AND METHOD: The present study was conducted between January 2006 and December 2008 in the neonatal intensive care unit (NICU) at Queen Sirikit National Institute of Child Health. All infants > or = 36 weeks gestational age who were diagnosed as PPHN by echocardiogram and had an oxygenation index > or = 20 were included in the study. Oral sildenafil was given as per study protocol with a starting dose of 0.25-0.5 mg/kg/dose. Oxygenation index (OI), oxygen saturations (SpO2), alveolar arterial oxygen gradient (A-aDO2) and mean arterial blood pressure (MAP) were monitored serially. RESULTS: A total of 40 infants were diagnosed with PPHN during this period. Eleven infants were included in the present study. The initial median OI was 31.95 (24.25-48.25). All infants received standard therapy with mechanical ventilation, sedation and inotropic drugs. OI decreased 4.6% from base line after the first hour of starting oral sildenafil and progressively decreased by 13%, 27%, 37%, 41% and 90% at 2, 4, 6, 12 and 24 hours respectively. Oral sildenafil was discontinued in one infant. It was combined with inhaled iloprost in 2 infants due to systemic hypotension and with inhaled nitric oxide in one infant due to deterioration. One infant died during the present study. CONCLUSION: Oral sildenafil may be effective in improving oxygenation in some infants with persistent pulmonary hypertension of the newborn. Systemic hypotension was a cause for concern in the present study. Further studies are needed to assess the pharmacokinetics, efficacy and long-term side effects of this drug. PMID- 22043757 TI - Dengue classification: current WHO vs. the newly suggested classification for better clinical application? AB - INTRODUCTION: There has been confusion regarding the clinical classification of dengue. The current WHO classification used since the 70s classifies dengue into dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS). In 2009, a new classification of dengue proposed by WHO Tropical Disease Research (TDR) was published in the WHO TDR 2009 dengue guidelines. This new classification classifies dengue into dengue (D), dengue with warning signs (DW) and severe dengue (SD). OBJECTIVE: To compare the effectiveness in clinical management between the current WHO classification and the newly suggested classification (TDR) and to assess the 4 criteria of the DHF case definition of the current WHO classification for possible modification. MATERIAL AND METHOD: A prospective study of suspected dengue patients admitted to the Dengue Unit, Queen Sirikit National Institute of Child Health between June-August 2009 was done. All cases were managed according to the Thai National Dengue Guidelines 2008. The final diagnoses were based on the current WHO Classification together with dengue laboratory confirmation. TDR classification was applied later by the author, using the data from the present study case report forms of each patient. Statistical analysis comparing clinical and laboratory data between each group of patients was done by using SPSS version 14. RESULTS: Total 274 confirmed dengue patients and 24 non-dengue febrile illnesses (ND) were used for analysis. There were 180 DF (65.7%), 53 DHF grade I (19.3%), 19 DHF grade II (6.9%), 19 DHF grade II (6.9%) and 3 DHF grade IV (1.1%) as classified by the current WHO classification while the suggested TDR classified 85 (31%), 160 (58.4%) and 29 (1.1%) as D, DW and SD respectively. At least one of the warning signs were found in 50, 53.3, 83, 88.2, 100 and 100% of ND, DF, DHF grade I, DHF grade II, DHF grade III and DHF grade IV patients. Vomiting and abdominal pain were the 2 most common warning signs found in both ND and dengue patients. Intensive monitoring and careful medical and i.v. fluid management were needed for 94 DHF patients compared to 189 DW and SD patients by the new TDR classification. There were 8 DSS patients who had AST > 1,000U and one patient presented with encephalopathy. These 8 patients cannot be classified properly in the current WHO classification. One non-dengue patient who presented with gastrointestinal bleeding was classified as SD. Bleeding and/or positive tourniquet test was found in and 69.7% of DHF patients. Plasma leakage detected using hemoconcentration, chest x-ray (CXR) and ultrasonography. Hemoconcentration could detect plasma leakage in 44.7% and CXR added up evidence of plasma leakage to 86.3%. Ultrasonography was the most sensitive technique to add evidence of plasma leakage up to 100%. Platelet < or = 100,000 cells/mm3 was found in 93.5% of DHF patients. CONCLUSION: Current WHO classification is recommended for continuing use because the newly suggested TDR classification creates about 2 times the workload to health care personnel. In addition, the TDR classification needs dengue confirmatory tests. More than 90% of DHF defined by WHO case definition are dengue confirmed. However, current WHO classification needs to be modified for more simple and friendly use. The suggested modification is to address plasma leakage as the major criteria. Tourniquet test positive or bleeding symptoms can be considered as minor criteria. Unusual dengue is proposed to be added to the current WHO classification to cover those patients who do not fit with the current WHO classification. PMID- 22043758 TI - Stevens-Johnson syndrome in Thai children: a 29-year study. AB - BACKGROUND: Stevens-Johnson syndrome (SJS) is a rare and severe life-threatening hypersensitivity syndrome. The etiology is unclear but is associated with drug exposure or infections and frequently high morbidity and mortality. OBJECTIVE: To determine etiologies, treatments and complications of Stevens-Johnson syndrome (SJS) in children. MATERIAL AND METHOD: A retrospective descriptive study was performed at Queen Sirikit National Institute of Child Health during 1979 and 2007 (29-year study). The authors collected and separated data into three phases from 1979 to 1987, 1988 to 1997 and 1998 to 2007. Diagnosis was confirmed by pediatric dermatologists. RESULTS: There were 189 patients, 56 cases between 1979 1987, 72 cases between 1988-1997 and 61 cases between 1998-2007. The ratio of male to female was 1.6: 1. The range of age was from 2 months to 15 years old with a mean age of 5.5 years. One hundred and sixty-five cases (87%) had a history of drug taking before onset of the rash. The most common drugs exposure were antibiotics in 69 cases (42%), anticonvulsant drugs in 58 cases (35%), non steroids anti-inflammatory drugs in 8 cases (5%), antimalarial drugs in 4 cases (2%) and unknown drugs in 26 cases (16%). Mycoplasma infections were found in 5 cases (3%). One hundred and nine cases (58%) were treated with systemic corticosteroids. The corticosteroid treatment was increasing from 18% in the first phase to 64% and 87% in the second and third phase respectively. The overall complications were found in 38 cases (20%) included bacterial skin infections in 16 cases (8%), eye complications in 12 cases (6%), hepatitis in 4 cases (2%) and other complications in 6 cases (2%). Ten patients (5%) died from sepsis and underlying diseases. The mortality rate declined from 9% in the first phase to 1.5% in the third phase. CONCLUSION: Etiology of SJS in children was associated with drug exposure with the most commonly implicated drug being antibiotics and anticonvulsants. Corticosteroid may have a role in the treatment of SJS. PMID- 22043759 TI - Postpartum depression in the mothers of preterm infants at Queen Sirikit National Institute of Child Health. AB - OBJECTIVE: To study the prevalence of postpartum depression in the mothers of preterm infants at Queen Sirikit National Institute of Child Health. STUDY DESIGN: A cross-sectional descriptive study was conducted at 1 to 6 months after delivery in 41 postpartum women of healthy preterm infants at the high risk clinic, Queen Sirikit National Institute of Child Health during 1st January to 31st December 2006. Health-related, self-report (HRSR) scale and the diagnostic screening test for depression in a Thai population were used for evaluation. Prevalence rate was calculated and analyzed, using SPSS version 12.0. The results were presented in percentage. RESULTS: The authors found 41 postpartum women of healthy preterm infants at the high risk clinic, Queen Sirikit National Institute of Child Health. The prevalence of post-partum maternal depression of preterm infants was 22 percent. It was found that all of them (9 cases) met criteria of minor depressive disorders, which needed no emergency psychiatric treatment. The mean age of depressive mothers were under 20 years old. All of the depressive mothers, educational level was lower than bachelor degree. CONCLUSION: The prevalence of postpartum depression in mothers of preterm infants was 22 percent. All of them suffered from mild depression, this should raise concerns with physicians to take care and be prepared for proper management. PMID- 22043760 TI - In vitro activities of colistin and ampicillin/sulbactam against Acinetobacter baumannii. AB - OBJECTIVE: The aim of the present study was to examine the in vitro antimicrobial activity of colistin, and ampicillin/sulbactam against A. baumannii isolated from pediatric patients and to compare the susceptibility testing using disc diffusion with minimal inhibitory concentration (MIC) E-test method. MATERIAL AND METHOD: One hundred strains of A. baumannii from various clinical isolates were included in the present study. Antimicrobial susceptibilities of A. baumannii to colistin, ampicillin/sulbactam were determined by disc diffusion and minimal inhibitory concentration (MIC) using E-test method. The analysis was stratified by carbapenem resistance status. Sensitivity and specificity of the disc diffusion test compared to the MIC E-test were estimated. RESULTS: Ninety-seven strains of all isolates (97%) were sensitive to colistin using both disc diffusion and E test methods. In contrast, 41% and 34% of the isolates were sensitive to ampicillin/sulbactam by disc diffusion and MICE-test, respectively. The colistin MIC50 and MIC90 for A. baumannii were 0.38 and 1 microg/mL, respectively. The ampicillin/sulbactam MIC50 and MIC90 were 16 and 89.6 microg/mL, respectively. Based on the results of MIC E-test, ninety-eight (n = 49) and six (n = 3) percent of carbapenem-resistant A. baumannii (n = 50) were susceptible to colistin and ampicillin/sulbactam, respectively. Sensitivity and specificity of disc diffusion test compared to MIC E-test were 99% and 66.7% for colistin and 80.5% and 98.3% for ampicillin/sulbactam, respectively. CONCLUSION: The antimicrobial activities of colistin against A. baumannii isolates remained high for both cabapenem susceptible and -resistant strains. However, the in vitro activity of ampicillin/sulbactam against A. baumannii was low. Thus, a combination, rather than monotherapy, of ampicillin/sulbactam with other antibiotics is strongly recommended when dealing with A. baumannii infection. In addition, disc diffusion test appeared to be a useful screening method for susceptibility testing for colistin and ampicillin/sulbactam against A. baumanii. PMID- 22043761 TI - Growth and development of very low birth weight infants aged 18-24 months at Queen Sirikit National Institute of Child Health. AB - BACKGROUND: The number of very low birth weight (VLBW) births is increasing worldwide. Despite better care in recent years, they have a high incidence of delayed growth and development. There are no previous studies regarding the growth and development of these infants at Queen Sirikit National Institute of Child Health (QSNICH). OBJECTIVE: To study growth and developmental outcome of VLBW infants, aged 18-24 months who were discharged from QSNICH. MATERIAL AND METHOD: VLBW infants who were discharged from QSNICH during the year 2007 were recruited in the study. Patients with chromosomal abnormalities, major congenital anomalies, definite congenital infections and positive maternal anti-HIV tests were excluded. At the corrected age of 18-24 months, the parents were called upon to bring their infants for complete physical examination and developmental evaluation on 2 occasions, two months apart. RESULTS: There were 111 cases of VLBW infants who were discharged from QSNICH during the year 2007. Fifty-four patients were eligible for the present study. Thirty cases (55.56%) were contacted for the first examination. During this examination, there were 3 cases (10%) with low head circumference, 1 case (3.33%) with poor weight gain, 5 cases (16.67%) with visual defect, 1 case (3.33%) with moderately severe hearing loss, 1 case (3.33%) with cerebral palsy and 7 cases (23.33%) with delayed development. Twenty-one cases could be recalled for a second evaluation. Two of the 5 cases had delayed language development. There were no cases with hydrocephalous, blindness or profound hearing loss. CONCLUSION: VLBW infants at QSNICH had much better survival during recent years. Most of these survivors had normal growth and development. Those with delayed growth and development need aggressive intervention and long-term follow-up for enhancement of quality of their lives. PMID- 22043762 TI - Clinical presentations of pandemic 2009 influenza A (H1N1) virus infection in hospitalized Thai children. AB - BACKGROUND: A novel influenza A (H1N1) virus of swine origin caused human infection and acute respiratory illness in Mexico during the spring of 2009. After that, the virus spread globally, resulting in the influenza pandemic. OBJECTIVE: To observe the clinical manifestations of the 2009 pandemic influenza A (H1N1) and the epidemic waves of hospitalized children for a period of one year. MATERIAL AND METHOD: A prospective observational study of children under eighteen years old, confirmed having the 2009 pandemic influenza (H1N1) infection by real-time reverse-transcription-polymerase-chain-reaction (RT-PCR), admitted at Queen Sirikit National Institute of Child Health, Bangkok, Thailand during one year, from 1st June 2009 to 31st May 2010. RESULTS: A total of 83 pandemic influenza infected children were admitted during a one-year period. There were two waves of epidemic outbreak, the first wave from June to August 2009 and the second wave from January to February 2010. There were 47 cases of males (56.6%), with the highest attack rates among children 1-5 years of age (48.2%). The youngest case was a 29-day old girl. The correct provisional diagnosis of pandemic influenza infection are 39.5%, the other initial diagnosis are pneumonia, bronchiolitis, tonsillitis, encephalitis, and dengue infection. Most patients coming for care had typical, influenza-like symptoms with fever (98.8%), cough (92.6%) and rhinorrhea (74.1%). Systemic symptoms are frequent. Gastrointestinal symptoms (including vomiting (46.9%) and diarrhea (24.7%)) occur more commonly than seasonal influenza. Pneumonia is the most common complication (43.2%); other complications include bronchiolitis, hemoptysis, acute respiratory distress syndrome (ARDS) and encephalitis. In one case, a seven year old girl suffered from ARDS, sepsis, multi-organ dysfunction syndrome and ventilator associated pneumonia, but survived with some neurological sequelae. Radiographic findings included diffuse interstitial, alveolar infiltrates and some in lobar distributions. Apart from oseltamivir the other antibiotics included ceftriaxone, cefotaxime, amplicillin and azithromycin, were added for pneumonia. All patients in the present study survived. CONCLUSION: The burden and character of pandemic influenza infection in developing countries are still incompletely understood. Early therapy with oseltamivir in severely ill patients, without waiting for laboratory confirmation for diagnosis, will save patients from severe complications. PMID- 22043763 TI - Preliminary study on assessment of lead exposure in Thai children aged between 3 7 years old who live in Umphang district, Tak Province. AB - BACKGROUND: Centers of Disease Control of the United States of America (CDC) informs Ministry of Public Health, Thailand that up to 13% of Burmese refugee children who are transferred to the United States of America during 2007-2009 have elevated blood lead levels (EBLL, Blood Lead Level > or = 10 microg/dl). These are children from a number of refugee camps in Tak Province; two camps are near Umphang but other camps are not. In June 2008, CDC, the result of investigation of Centers for Disease Control/Thailand Ministry of Public Health Collaboration (CDC/TUC) and International Organization for Migration, Thailand indicates that 33 of 64 children aged 6 months to 15 years (5.1%) who live in Mae La, Umpiem and Nupo camps have elevated blood lead level. However, no study on how Thai children who live nearby those camps are exposed to lead. Subsequently, Queen Sirikit National Institute of Child Health, Bangkok, Thailand contacts relevant organizations in Tak Province in order to investigate lead exposure and evaluate health status of Thai children who live close to Burmese refugee camps. OBJECTIVE: 1) Evaluation of lead exposure of Thai children who live nearby Burmese refugee camps; 2) Assessment of risk factors on lead exposure of the children as mentioned above. MATERIAL AND METHOD: The present study adopts a retrospective study based on information gathered from health assessment on 213 Thai children aged between 3-7 years old who live nearby Burmese refugee camps. The health assessment was conducted from April 30th, 2010 to May 5th, 2010. The information is from 3 sources. The first source is from blood sampling in order to assess lead level and ferritin level. The next source is from interview of persons who provide primary care in order to identify risk factors on lead exposure of target children. The last source is from physical examination and developmental assessment conducted by pediatricians and special nurses for child development in order to identify health and developmental problems. RESULTS: The population of the present study was 213 of Thai children are 3-7 years old, average age is 54.54 +/- 12.41 months-old. The average blood lead level is 7.71 +/- 4.62 microg/dl (range = 3-25 microg/dl). Elevated blood lead levels of all populations show that 57 children (26%) have blood lead level at 10 microg/dl or more. Analysis of odds by controlling all risk factors (adjusted OR) that effect on blood lead level (> or =10 microg/dl) indicates that only gender and source of drinking water are risk factors. To clarify, male children would have 2.8 times higher risk than female children. Children who drink water from tap and canal have 15 times and 72 times, respectively, higher risk than children drinking from bottle water. CONCLUSION: The result of the present study shows that 1 of 4 of Thai children at Umphang district, Tak Province who lived near Burmese refugee camps aged between 3-7 years old have blood lead level higher than concerning level. Thus, it is necessary to identify risk factors on lead exposure and policy of blood lead screening in some areas in Thailand. PMID- 22043764 TI - Knowledge, attitudes and practices relating to plastic containers for food and drinks. AB - BACKGROUND: Plastic is widely used in daily life especially as food and drink containers. If these containers are used inappropriately, some chemicals such as bisphenol A, phthalate, and styrene from plastic may accumulate and impair organ function. OBJECTIVE: To assess knowledge, attitudes, and practices relating to plastic containers for food and drinks among parents and health personnel. MATERIAL AND METHOD: 100 parents and 100 health personnel from Queen Sirikit National Institute of Child Health are included in the present study. The questionnaires which contained 6 parts measuring knowledge, attitudes and practices about plastic containers for food and drinks are used to collect the data. RESULTS: There are no differences in knowledge, attitudes and practices relating to plastic containers between parents and health personnel. Even though, 80 percent of participants usually use plastic containers for food and drinks, their knowledge about plastic is inadequate. CONCLUSION: Parents and health personnel are aware of health effects of plastic containers, but they do not know how to use and purchase plastics properly. PMID- 22043765 TI - Metabolic syndrome in obese Thai children and adolescents. AB - BACKGROUND: The prevalence of childhood obesity in Thailand is increasing. Obese children are at risk of metabolic syndrome. OBJECTIVE: To determine the prevalence of metabolic syndrome in obese Thai children with various degrees of obesity and its association with severity of obesity, insulin resistance and C reactive protein. MATERIAL AND METHOD: A cross-sectional study of 89 obese Thai children and adolescents was conducted at the Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University. Family histories of diabetes mellitus, hypertension, obesity and dyslipidemia were assessed. Anthropometry and cardiovascular risks including levels of fasting blood sugar, oral glucose tolerance test, insulin, C-reactive protein (CRP) and lipid profile were determined. Metabolic syndrome was defined using International Diabetes Federation criteria adjusted for age and sex. Univariate and logistic regression analysis were used for identification of the independent associated factors. RESULTS: The overall prevalence of metabolic syndrome in the present study was 16.9%. The percentages of metabolic syndrome in subjects with moderate, severe and morbid obesity were 10.5, 23.1 and 22.2 respectively. Univariate analysis revealed that metabolic syndrome had a statistically significant association with insulin level over 25 microIU/mL, homeostasis model for assessment of insulin resistance (HOMA-IR) equal to 3.16 or more and CRP over 3 mg/L. Logistic regression analysis revealed that only insulin level over 25 microIU/mL was independently associated with metabolic syndrome (OR 7.24; 95% CI: 2.01-26.10). CONCLUSION: The prevalence of metabolic syndrome is high among obese Thai children and adolescents. Prevention and proper management of metabolic syndrome including treatment of obesity should be considered in obese children. PMID- 22043766 TI - Nutritional status of pediatric patients with congenital heart disease: pre- and post cardiac surgery. AB - BACKGROUND: Malnutrition is common in infants and children with congenital heart disease (CHD). Cardiac surgery has improved patient survival and nutritional status. OBJECTIVE: To evaluate the impact of cardiac surgery on nutritional status of pediatric patients with CHD. MATERIAL AND METHOD: A prospective cohort study was conducted in pediatric patients with CHD, admitted for cardiac surgery at Queen Sirikit National Institute of Child Health (QSNICH), Bangkok, from August 1st, 2002 to 2003. Demographic data, cardiac and related problems were obtained before operation. Anthropometry was performed at the presentation and post cardiac surgery. Nutritional status was assessed by Z-score of weight for age (ZWA), weight for height (ZWH) and height for age (ZHA). Malnutrition was defined as Z-score <- 2 and compared pre- and post-operation using Chi-square. Paired t-test was used to compare mean Z-score and p-value < 0.05 was statistically significant. RESULTS: All of 161 pediatric patients with CHD undergoing cardiac surgery were 41% males and 59% females. Patients' age ranged from 1 month to 15 years. The related problems included low birth weight (28%) and feeding problem (58%). The most common CHD was ventricular septal defect (29%). The nutritional status of the patients before surgery was defined as normal 57%, malnutrition 40% and over-nutrition 3%. Malnutrition included underweight 28%, wasting 22% and stunting 16%. Post cardiac surgery, the means of ZWA, ZWH and ZHA were significantly increased and the prevalence of underweight and wasting were decreased to 17% and 6% respectively, with statistically significant from the baseline (p < 0.05). CONCLUSION: Malnutrition was found in 40% of pediatric patients with CHD and cardiac surgery has a significant positive effect on weight gain and nutritional status. PMID- 22043767 TI - Post-traumatic stress disorder in children after the tsunami disaster in Thailand: a 5-year follow-up. AB - BACKGROUND: Children may suffer from post-traumatic stress disorder after disaster. There was a severe tsunami following an undersea earthquake off the Sumatra coast of Indonesia. There were 20,000 children in 6 southwestern provinces of Thailand who were possibly affected. OBJECTIVE: To study the prevalence of post-traumatic stress disorder (PTSD) in Thai students in the area affected by the December 26th, 2004 tsunami disaster, Thailand. MATERIAL AND METHOD: One thousand six hundred and fifteen surviving students from two schools in Takua Pa district located in Phang-nga Province, Thailand participated in this longitudinal study. Screening was done by using Pediatric Symptom Checklists part II (PSC-II), Childhood Depressive Intervention (CDI) and the Revised Child Impact of Events Scales (CRIES 8). PTSD was diagnosed by child and adolescent psychiatrists by using criteria of DSM-IV. The intervention included psychological first aid, psycho-education, cognitive-behavioral therapy, medication in severe cases, group support for students, parents and teachers which was done, beginning at 10 days after the tsunami disaster. Data were analyzed by using SPSS version 12.0. RESULTS: The prevalence rates of PTSD in the students facing the tsunami disaster in the study group were 573, 46.1, 31.6, 7.6, 4.5, 3.9 and 2.7% at 6 weeks, 6 months, 1 year, 2 years, 3 years, 4 years and 5 years after the disaster, respectively. Female to male ratio was 1.7: 1. The peak age was 9-10 years old. The top five on the list of symptoms in PTSD were distress with cue, intrusive thought, functioning impairment, startled response, terrified and hyper vigilance. Seven cases (3.1%) were diagnosed partial PTSD, still exhibited a wide range of PTSD symptoms but did not fulfill the DSM-IV diagnostic criteria. The top five on the list of symptoms in partial PTSD were avoiding thought/feelings, terrified, avoiding place/activities, distress with cue and startled response. CONCLUSION: The prevalence of PTSD among tsunami victims was 57.3% at 6 weeks after the disaster. It declined sharply at 2 years after the event. Despite receiving financial, rehabilitation and mental health support, 2.7% of the victims continued to suffer from PTSD 5 years after the disaster. PMID- 22043768 TI - The effectiveness of brief psychosocial screening in identifying behavioral problems in children. AB - BACKGROUND: Using screening tools to enhance early detection of psychosocial problems can lead to timely intervention and appropriate referral to general practices. OBJECTIVE: To assess whether the Thai version of Pediatric Symptom Checklist (PSC) is suitable for screening of psychosocial dysfunction. MATERIAL AND METHOD: A cross sectional study was conducted among 160 children aged 6-11 years seeking care at Queen Sirikit National Institute of Child Health from November 2006 to December 2007. Parents were asked to complete the Thai version of the Pediatric Symptom Checklist (PSC) questionnaire and the Thai Youth Behavior Checklist (TYC). Sensitivity specificity, positive and negative predictive value were analyzed and reported. RESULTS: The area under the receiver operation characteristic (ROC) curve, using the TYC as a gold standard, was 0.895. The cut-off score of 16 was appropriate for early detection of the psychosocial dysfunction. At this cut-off score, the sensitivity was 83.51%, the specificity was 79.37%, the positive predictive value was 86.17% and the negative predictive value for detecting psychosocial dysfunction among children was 75.76%. CONCLUSION: The authors' findings suggested that the Thai version, parent completed, PSC may be a useful psychosocial screening tool for the children aged 6-11 years with the recommended cut-off score of 16. PMID- 22043769 TI - Childhood myasthenia gravis: clinical features and outcomes. AB - OBJECTIVE: To study the clinical features, treatment, outcome and factors that affected the outcome of myasthenia gravis (MG) in children. MATERIAL AND METHOD: Children aged 16 years or less with diagnosed myasthenia gravis (MG) seen at Queen Sirikit National Institute of Child Health over a 15-year period with a minimum follow-up of 6 months were reviewed. Demographic, clinical characteristics, treatment and the outcome were analyzed. RESULTS: One hundred and nineteen MG patients, 100 patients (84%) were ocular MG (OMG) and 19 patients (16%) were generalized MG (GMG). Median age of onset was 4.1 years. OMG patients had the age of onset earlier than GMG patients (p = 0.01). Female to male ratio was 1.8: 1. Ptosis was a clinical feature in 99%, accompanied with ophthalmoplegia in 63%, diplopia in 19.3%, extremity weakness in 13.4%, respiratory muscle weakness in 9%, head tilt in 10.1%, dysphagia in 7.5%, hyperthyroidism in 3.4% and epilepsy in 2.5%. One hundred and six patients who had ptosis as the initial symptom 67% were bilateral ptosis, 33% were unilateral ptosis, 10 patients progressed to GMG in 2 years. Almost all patients were treated with pyridostigmine and prednisolone. At the end of follow-up, 60.5% had pharmacological remission for more than 3 months, 18.5% had complete remission without medication. No definite factors associated with the remission were identified. CONCLUSION: OMG is the majority of MG patients and the age of onset is earlier than GMG. Early treatment by prednisolone may have the favorable effect on OMG in the progression to GMG and subsequent involvement to the other eye. PMID- 22043770 TI - Long-term effects of short-acting methylphenidate on growth rates of children with attention deficit hyperactivity disorder at Queen Sirikit National Institute of Child Health. AB - BACKGROUND: Methylphenidate (MPH) is generally considered to be first-line treatment for the core symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Long-term administration of MPH in childhood may have adverse effects on growth. OBJECTIVE: To determine the effect of long-term, short-acting MPH medication on growth. MATERIAL AND METHOD: A retrospective descriptive study was employed by gathering the data of patients who were diagnosed as ADHD by child psychiatrists at the child and adolescent clinic, Queen Sirikit National Institute of Child Health. Subjects were patients received the first dose of short-acting methylphenidate from January 1st 2000 to December 31st 2007 and continued medication for at least 1 year. Data about height and weight were reviewed at the beginning of short-acting MPH medication, 6 months (mo), 1 yr, 2 yr, 3 yr, 4 yr, 5 yr, 6 yr and 7 yr interval. Collecting data was interpreted with INMU-Nutri Stat software program. Paired t-test was used to compare Z score of height and weight at different time points. RESULTS: There were 96 cases in the present study; the ratio of male to female was 3.6: 1. The first dose of short-acting methylphenidate was started at an average age of 8.62 +/- 1.70 years. Average drug dose ranged from 0.41-0.49 mg/kg/day. The data evaluated at 6 mo, 1 year 2 years, 3 years, 4 years and 5 years after drug use found that weight was not affected. Height decreased at 6 mo. after drug use (p < 0.05) but long term treatment was not statistically significant. CONCLUSION: Prolonged medication with short-acting MPH has shown to have minimal impact on height only at the first 6 months; however, catch up growth was detected during adolescent period. PMID- 22043771 TI - Clinical and epidemiological characteristics of respiratory syncytial virus and influenza virus associated hospitalization in urban Thai infants. AB - BACKGROUND: Respiratory syncytial virus (RSV) and influenza infections are among the leading cause of hospitalized lower respiratory tract infections (LRTI) in children especially among those younger than 1 year of age. Few descriptions of these 2 important viruses in Thai children less than 1 year of age have been published. MATERIAL AND METHOD: The authors conducted a prospective study of children 1-12 months old hospitalized at a pediatric tertiary-care hospital in Bangkok with LRTI during the period December 2007 to August 2009. Respiratory specimens were tested for influenza A/B virus and RSV using a reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Twenty-six (7.3%) had RT-PCR positive for influenza and 104 (29.4%) for RSV from 354 infants. Clinical diagnoses included pneumonia (73.4%), bronchiolitis (17.55%), croup (6.5%) and bronchitis (2.5%) and were similar among groups except the proportion of croup was significantly lower in RSV (p = .018). The proportion of RSV infection was highest between July and October (42-76%). RSV patients were more likely to present with higher temperature than the negative RT-PCR patients (p = .031). Oseltamivir was prescribed in 7.7% of influenza infections. Intravenous antibiotics were prescribed in 69.2%, 56.7% and 60.7% of the influenza, RSV and negative group respectively (p = .736). Percentages of patients requiring mechanical ventilation were 3.8, 6.7 and 6.3% among the influenza, RSV and negative group respectively (p = .861). Three patients died: 2 from RSV and 1 from the negative group. All three fatality cases had existing co-morbidity. CONCLUSION: A high proportion of RSV was detected in infants hospitalized with LRTI especially during July to October. High proportion of antibiotic prescription and relatively low rate of oseltamivir treatment were identified. Surveillance data and the availability of a rapid and reliable viral diagnostic test may help guide treatment, thereby improve outcome of this vulnerable population. PMID- 22043772 TI - Correlation between serum and salivary phenytoin concentrations in Thai epileptic children. AB - OBJECTIVE: To study the correlation between serum and salivary phenytoin concentration in Thai epileptic children. MATERIAL AND METHOD: Children aged 5 to 12 years with diagnosed epilepsy who received phenytoin monotherapy seen in the neurological clinic at Queen Sirikit National Institute of Child Health were studied. The recruited patients were required to have good compliance, normal albumin level, and no evidence of cancer, HIV infection, hepatic, renal and salivary glands disease. Blood and saliva samples were collected and measured phenytoin level by fluorescence-polarization immunoassay technique. RESULTS: Thirty patients, 19 males and 11 females, were studied. The average (mean +/- SD) age and weight were 8.24 +/- 2.09 years and 27.76 +/- 9.86 Kilograms. Both serum and salivary phenytoin levels correlated with phenytoin doses as exponential type (R2 = 0.4188, 0.3682, respectively). Equations for describing serum and salivary phenytoin levels by phenytoin dose were y = 0.7403e(0.3952x) and y = 0.1431e(0.3072x) respectively. Serum and salivary phenytoin levels were closely correlated as linear type (R = 0.880, R2 = 0.967). The obtained equation of this relationship was y = 10.165x, where y = serum phenytoin level and x = salivary phenytoin level. Adverse drug reactions were found in 5 patients (6.6%), horizontal nystagmus 2 cases, hirsutism 2 cases and gingival hyperplasia 1 case. CONCLUSION: High correlation between serum and salivary phenytoin levels supported the use of saliva instead of blood for phenytoin monitoring in Thai children which were difficult in blood collection and had psychological trauma. The obtained equations in the present study could be applied for adjusting the dosage regimen and monitoring by using salivary phenytoin level in clinical practice. PMID- 22043773 TI - Are infants exclusively breastfed up to 6 months of age at risk of anemia? AB - OBJECTIVE: To compare the incidence of anemia between infants who received exclusive breast feeding (EBF) up to the age of 6 months and those who did not. MATERIAL AND METHOD: A cross sectional survey was conducted to examine the physical growth, incidence of anemia, mean hematocrit (Hct) level and other red cell indices among 6-month-old infants visiting a well-child clinic at QSNICH and Ramathibodi Hospital. RESULTS: 63 infants were included in the present study: 24 (38%) EBF group; and 39 (62%) non-EBF group. Mean Hct of EBF group was 34.5 +/- 1.7 and Non-EBF group was 35.1 +/- 2.3% respectively. The prevalence of anemia in the EBF group was 4.2%, non-EBF group was 12.8%. Even though the findings were not statistically significant, the authors found that the red blood cell indices in an anemic infant in the EBF group were not caused by iron deficiency, while the 4 of 5 anemic infants in the Non-EBF group were related to iron deficiency anemia (80%). Other growth parameters were compared between the two groups. CONCLUSION: The present study did not show statistical difference regarding the different hematocrit and other red blood cell indices including other fundamental background but the prevalence of anemia appeared to be higher among Non-EBF compared to EBF up to 6 months. The cause of anemia was not related to iron deficiency anemia in the EBF group compared to those higher and related to iron deficiency anemia in the Non-EBF group. SUGGESTION: EBF up to 6 months should be advocated given its substantial health benefit and does not increase the risk of anemia. Nevertheless, it is essential that mothers receive adequate nutritional supplement including iron during pregnancy and lactation period. PMID- 22043774 TI - Improvement of ambulatory function with multilevel soft tissue surgery in children with spastic diplegic cerebral palsy. AB - Single Event Multilevel soft tissue surgery in spastic diplegic children also was effective for improving ambulatory function obviously as multilevel bone and soft tissue surgery. Just muscle and tendon surgery seem to be enough for better lever arm dysfunction of the lower extremity. It has safe, simple and rapid recovery. OBJECTIVE: Gross Motor Functional Classification System (GMFCS) improvement after single event multilevel soft tissue surgery had been observed in these study groups of patients. MATERIAL AND METHOD: Retrospective review in 93 spastic diplegic children who were more than 3 years old, had ability to understand communication, at least leaned sitting and one-hand gross function ability had been operated on by single event multilevel soft tissue surgery. GMFCS was assessed at the time of pre-operation and 6-12 months after operation. Analyzing GMFCS change was performed by statistics. RESULTS: Average 7 site surgery per one patient, 84% GMFCS level improvement and 16% GMFCS level non-improvement were reported. Nine cases (9.7%) were improved 2 level of GMFCS and 74% improved 1 level. GMFCS level compared between pre- and post surgery had changed by the significant statistic (p < 0.001). The average GMFCS level improvement for all groups was 0.93 level. The average age in the improved group (75 months old) was less than the non-improved group (92 month old), was a trend difference in statistic (p = 0.032). CONCLUSION: Single Event Multilevel Soft tissue surgery was effective in improving the GMFCS level average 1 level. It changed ambulatory function of spastic diplegic CP children obviously, immediately and safely. Younger age might get more benefit than older children. PMID- 22043775 TI - Clinical features and outcome of childhood optic neuritis at Queen Sirikit National Institute of Child Health. AB - OBJECTIVE: To study the clinical features, treatment, outcome and factors affecting the outcome of optic neuritis in children. MATERIAL AND METHOD: Children under 16 years of age diagnosed with optic neuritis (ON) at Queen Sirikit National Institute of Child Health over an 11-year period were reviewed. Demographic data, clinical characteristics, treatment and the outcome were analyzed. RESULTS: Thirty-one patients fulfilled the inclusion criteria. Mean age of onset was 9.2 years. Female to male ratio was 1.8:1. All cases had vision loss, bilateral 74.2% and monocular 25.8%, including decreased color vision 35% disc edema 54.8% and ocular pain 38.7%. The mean duration of follow-up was 20.38 months. The final diagnosis of these patients were 2 multiple sclerosis (MS), 2 neuromyelitis optica (NMO), 3 acute disseminated encephalomyelitis (ADEM) and 24 or isolated optic neuritis (ION). There was no statistically significant difference in gender, age of onset, number of ocular involvement, severity of visual acuity impairment, presented preceding infection, associated symptoms, CSF pleocytosis, high protein in CSF, abnormal brain or eye MRI. 93.3% of patients had clinical improvement, including 70% complete recovery visual acuity of both eyes. The statistically significance was that complete remission in females was more than in males. CONCLUSION: Childhood optic neuritis had bilateral vision loss and complete recovery. Females with optic neuritis had statistical significance with complete recovery, more than males. PMID- 22043776 TI - Immunizing children aged 9 to 15 months with live attenuated SA14-14-2 Japanese encephalitis vaccine in Thailand. AB - The authors aimed to evaluate the safety and immunogenicity of a live attenuated SA14-14-2 Japanese Encephalitis (JE) vaccine in healthy Thai infants. One hundred and fifty subjects aged 9-15 months were vaccinated with one dose of this vaccine. Regarding the vaccine safety, during the 28-day post-vaccination follow up, no vaccine-related serious adverse events were reported. In terms of immunogenicity, the sero-conversion rate of a single dose vaccination was 95% (95% CI, 90.0-97.6%) within 90 days after vaccination and the geometric mean titer (GMT) was 66.1. Eight subjects with JE seronegative on days 28-35 post vaccination became sero-positive on day 90. Seven subjects who remained sero negative during days 28-35 and day 90 post-vaccination were successfully sero converted after receiving a second dose 3 months later. Thus, two doses of this JE vaccine resulted in a 100% (95% CI, 97.3-100%) sero-conversion rate with the GMT of 260.8. Eight children with GMTs lower than protective level after a single vaccination demonstrated a booster response with GMT of 1237 after the second dose of JE vaccination. In conclusion, the live attenuated SA14-14-2 vaccine was safe, well tolerated and highly immunogenic with 95% and 100% sero-conversion rate after one and two doses, respectively. Nevertheless, its long-term immune response and possible influences from natural dengue infection requires further evaluation. PMID- 22043777 TI - Predictive factor of severe renal involvement in children with Henoch-Schoenlein purpura. AB - OBJECTIVE: To find out which of the clinical manifestations or laboratory findings is the predictive factor of severe renal involvement in children with Henoch-Schoenlein purpura (HSP). MATERIAL AND METHOD: Data of clinical manifestations and laboratory findings in children with HSP at Queen Sirikit National Institute of Child Health between January 2003-December 2007 were prospectively collected and analyzed. RESULTS: There were 168 cases, 86 boys and 82 girls (M:F ratio= 1.05:1), the age ranged from 2 to 15 years (mean +/- SD = 6.9 +/- 2.6 years, mode = 6.8 years). Development of severe renal involvement was identified in 11 cases (6.6%). Abnormal urinalysis (microscopic hematuria or proteinuria) on the day of diagnosis was statistically significant (p < 0.001) as a predictive factor of severe renal involvement during follow-up. Early systemic corticosteroid administration due to severe abdominal pain was not statistically significantly different between the patients with or without severe renal involvement. CONCLUSION: Abnormal urinalysis on the day of diagnosis was the only predictive factor of severe renal involvement in children with Henoch-Schoenlein purpura. Early systemic corticosteroid administration due to severe abdominal pain did not prevent severe renal involvement. PMID- 22043778 TI - Acute hematogenous osteomyelitis and septic arthritis in children: clinical characteristics and outcomes study. AB - OBJECTIVE: To evaluate the clinical features, causative pathogens and outcomes related to acute hematogenous osteomyelitis and septic arthritis in pediatric patients. MATERIAL AND METHOD: The authors conducted a retrospective cohort study of patients under 15 years of age with diagnosis of acute hematogenous osteomyelitis (AHO) and/or septic arthritis (SA), treated at Queen Sirikit National Institute of Child Health from 1996 to 2006. Demographic data, clinical characteristics, bacterial spectrum, and outcomes were collected. Potential risk factors for osteoarticular sequelae in the patients who had more than 2 years of follow-up were analyzed. RESULTS: One hundred and twenty-nine patients met the diagnostic criteria which included 51 cases with SA, 35 cases with AHO and 37 cases with both SA and AHO. The patient's age ranged between 1 day and 13 years 4 months, comprising 37 (28.6%) of newborns, 28 (21.7%) of > 1-12 months, 18 (14%) of > 1-3 years and 46 (35.7%) of > 3-15 years. Causative bacteria were found in 103 of 129 patients (80%), the two most common pathogens were methicillin sensitive Staphylococcus aureus (MSSA) in 48 (46.6%) and methicillin-resistant Staphylococcus aureus (MRSA) in 18 (17.5%) cases. The initial temperature on admission day was high (> 37.5 degrees C) in only one-third of newborns, one-half of infants and two-thirds of the older group. The duration of antibiotic administration ranged between 21 and 56 days (mean 42 days). Arthrotomy or drainage and bone or joint aspiration underwent in 62% and 17% of cases respectively. Outcomes of 79 patients who had more than 2 years of follow-up identified osteoarticular sequelae in 23 patients (29%) that consisted of avascular necrosis of epiphysis, limb-length discrepancy and pathologic fractures. Univariate analysis for potential risk factors compared between sequelae and without sequelae groups demonstrated significant association with more than 1 week duration of presenting symptoms, newborn age group, hip joint infection, infection with MRSA and more than 3 days delayed treatment with appropriate antibiotics. CONCLUSION: MSSA was the most common bacterial pathogen causing pediatric osteoarticular infections in all age groups but was second to MRSA in the newborn group. Osteoarticular sequelae were avascular necrosis of epiphysis, limb length discrepancy, and pathologic fracture which were significantly related to longer duration of presenting symptoms, newborn age group, hip joint involvement, MRSA infection and delayed administration of appropriate antibiotics. PMID- 22043779 TI - Combined aortic and pulmonic valvular stenosis: report of 2 cases. AB - OBJECTIVE: To report 2 cases of severe combined aortic and pulmonic valvular stenosis. MATERIAL AND METHOD: To find patients with a diagnosis of severe combined aortic and pulmonic valvular stenosis, the authors searched in the patient profile at the cardiology unit, Queen Sirikit National Institute of Child Health (QSNICH) from 1995 to 2010. RESULTS: There are 2 cases of severe combined aortic and pulmonic valvular stenosis from 19,416 case records of pediatric cardiac patients. The first one is a 9-year-old girl and the other is a male neonate. The interval between the presentations of these two cases was 10 years. The older patient, who had associated moderate aortic regurgitation, underwent aortic root replacement and pulmonic valvulotomy in the year 2000. The neonate, who presented in 2010 had undergone bilateral percutaneous balloon aortic and pulmonic valvuloplasty and required repeated balloon aortic valvuloplasty at the age of two months. Both patients responded well to treatment and were asymptomatic at the last follow-up of 10 years and 6 months respectively after treatment. CONCLUSION: Combined aortic and pulmonic valvular stenosis is a very rare congenital heart disease. The prevalence is 0.01% of congenital heart disease at QSNICH. Bilateral balloon valvuloplasty of aortic and pulmonic valve is effectively performed in this rare congenital heart disease and can be done safely in a sick neonate. PMID- 22043780 TI - Hepatocellular carcinoma in children presents with massive upper gastrointestinal bleeding: a case report. AB - Hepatocellular carcinoma (HCC) is a very rare pediatric tumor. The incidence is 0.5-1.0 cases per million children. The most common clinical sign is abdominal mass. HCC often develops in the presence of underlying liver disease and cirrhosis, especially viral hepatitis. The authors hereby report a 9-year-old girl with hepatocellular carcinoma associated with positive hepatitis B surface antigen at Queen Sirikit National Institute of Child Health. She was admitted because of massive upper gastrointestinal bleeding (UGIB) due to esophageal varices. Multiple sessions of esophagogastroscopy with sclerotherapy banding ligation and glue injection of esophageal varices were performed but she still had massive UGIB. Sengstaken-Blakemore tube was used, after which she developed a ruptured esophagus. Finally she passed away. Liver necropsy was performed and diagnosed as HCC. PMID- 22043781 TI - Invasive Vibrio cholerae non-O1 non-0139 infection in a thalassemic child. AB - Invasive, extra-intestinal infection with Vibrio cholerae non-O1, non-O139 is rare especially among children. Herein the authors report a 12-year-old girl with underlying beta-thalassemia status post-splenectomy presenting with V. cholerae non-O1, non-O139 gastroenteritis with concomitant septicemia. The pathogen was identified from stool and blood culture and the patient recovered uneventfully after antimicrobial and supportive therapy. A review and comparison of clinical manifestations and outcomes with the previous four cases of invasive V. cholerae non-O1, non-O139 in postsplenectomy thalassemic pediatric patients is reported. PMID- 22043782 TI - Report 2 cases of congenital factor XII deficiency: a rare coagulation disorder. AB - Factor XII (F.XII, Hageman factor) is one of the contact system factors which initiates an intrinsic coagulation pathway. But its definite role is still unclear, because many cases of severe F.XII deficiency experience thrombotic events instead of a bleeding problem. Moreover most of them are asymptomatic. There have only been a few reports of F.XII deficiency in Thailand. The author reports two cases of congenital F.XII deficiency in Thai children. PMID- 22043783 TI - Dengue hemorrhagic fever grade III with diabetic ketoacidosis: a case report. AB - A 16-year-old, previously healthy Thai girl presented with DHF grade III. Fifteen hours after the first episode of shock, she had received an excessive amount of crystalloid isotonic solution and 20 ml per kilograms of Dextran-40 however she still had persistently rapid pulse rate and high hematocrit but also had polyuria with more than 4 ml/kg/hr of urine output. She was re-evaluated. Clinical signs showed severe dehydration with some ascites without signs of pleural effusion. Blood gas revealed increased anion gap metabolic acidosis. The cause of polyuria and metabolic acidosis was identified with hyperglycemia, ketouria and glucosuria. Afterwards she was diagnosed and treated as DHF grade III and DKA. Besides insulin administration, fluid resuscitation was very crucial. Intravenous fluid rehydration was needed while the unnecessary extra-volume could cause massive plasma leakage and later on fluid overload. Volume replacement was adjusted to degree of dehydration when signs of volume overload were monitored closely. She was out of DKA at 14 hours after the start of insulin and the intravenous fluid was stopped at 27 hours (36 hours after the first episode of shock). The final diagnosis was DHF grade III, diabetes mellitus with DKA and hepatitis. PMID- 22043784 TI - [Genetic engineering of Pichia pastoris expression system for improved secretion of heterologous proteins--a review]. AB - Due to the potential for producing soluble, correctly folded protein with high yield, Pichia pastoris is currently one of the most effective hosts for the expression of heterologous proteins. However, limitations of expression efficiency are often reported for many different heterologous proteins. Accumulating evidences suggest that protein folding and processing of heterologous protein is a major bottleneck during secretion process in yeast. Apart from optimization of the fermentation process, the current strategies for strain engineering for improving protein secretion are focused mainly on folding and processing, and systematic engineering by high-throughput screening for potential secretion enhancers. This article reviews the genetic engineering progresses of these aspects. PMID- 22043785 TI - [Research progress of VBNC bacteria--a review]. AB - The viable but non-culturable (VBNC) is a microbial state, in which microbial cells are metabolically active but cannot be cultivated by routine methods. In this article, we address the formation mechanism, change and variety, resuscitation, research significance and application prospects of VBNC state in bacteria. Furthermore, we report our research findings on VBNC state of bacteria in the past 10 years, including resuscitation, culturable, phylogenetic relationship and potential functions. PMID- 22043786 TI - [Uncultivated host-specific Bacteroidales markers identification of fecal source pollution--a review]. AB - Bacteroidales has been proposed as a fecal pollution indicator. microbial source tracking (MST) based on Bacteroidales host-specific gene markers has recently been applied in the fecal pollution identification, which does not require culturing the fecal pollution indicator organisms. This method needs to design specific primers. The primers are designed based on Bacteroidales specific 16S rRNA gene. Once a pair of specific primers was amplified, the fecal pollution can be identified. In this paper, the progress of specific primers of Bacteroidales in human, swine, ruminant feces were reviewed and discussed. The advantages and disadvantages were put forward. Future researchers should be focused on the new biological markers and the combination of different MST methods. PMID- 22043787 TI - [Origin and evolution of canine parvovirus--a review]. AB - Canine parvovirus (CPV-2), first recognized in 1978 as a new pathogen of dogs, was probably derived from a very closely related virus in cats, feline panleukopaenia virus (FPLV) or a closely related carnivore parvovirus (FPLV-like virus). CPV-2 is responsible for either myocarditis or fatal gastroenteritis in pups with high morbidity and mortality. Shortly after its emergence, CPV-2 has become endemic in the global dog population. The original CPV-2 continued to evolve, and was subsequently replaced by three different but closely related antigenic variants, designated CPV-2a, CPV-2b and CPV-2c, which now coexist in dog populations worldwide. The genetic and antigenic variation in CPV-2 also correlated with changes in the host range and tissue tropisms of the virus. Here, we reviewed variation and evolution of CPV-2 in past 30 years and discussed CPV-2 as an important model to study virus evolution. PMID- 22043788 TI - [Microbial diversity in sediments of core HS-PC 500 from Shenhu Area, northern South China Sea]. AB - OBJECTIVE: We studied the microbial diversity in the sediments of different depth in a gravity piston core HS-PC500 from Shenhu Area, the northern of South China Sea. METHODS: Total DNA was extracted from the sedimental materials; the archaeal and bacterial 16S rRNA gene sequences were amplified. The clone libraries were used to analyze the microbial systematic development. RESULTS: Group C3 was the predominant archaeal group in the top layer (0-5 cm bsf) sediments, and the Marine Benthic Group (MBG)-B group became predominant with depth, reaching 38.9% and 62.5% in the middle (350-355 cm bsf) and bottom (790-795 cm bsf) sediments. Some belonged to MBG-A, Miscellaneous Crenarchaeotic Group (MCG), Thermoprotei, Novel Group Crenarchaeota (NGC), Halobacteriales, MBG-E, South African Gold Mine Euryarchaeotic Group (SAGMEG). Proteobacteria was the dominant bacterial group in the top of the core, but became minor deeper within the sediments. As depth increased, Chloroflexi and candidate division JS1 became the predominant groups and reached up to 28.1%, 29.2% and 39%, 24.7%. Other sequences respectively belonged to Nitrospirae, Actinobacteria, Acidobacteria, candidate division OP8, Spirochaetes, candidate division TM6, Deferribacteres and Plantomycete. CONCLUSION: Down-core variation in microbial abundance in sediments of HS-PC500 was consistent with the changes of methane concentration in the same core; the lower microbial abundance might be probably due to lower total organic carbon (TOC) in sediments; However, microbial diversity was relatively high and community structure varied apparently with depth; the community was dominated by clusters that was dominated in sulfate reduction condition, suggesting that microbial metabolization played very important role in the material cycle of marine sediments. PMID- 22043789 TI - [Analysis of the flgD and figE genes regulated by diffusible signal factor in Xanthomonas oryzae pv. oryzicola]. AB - OBJECTIVE: To investigate functions of flgDxoc and flgExoc genes regulated by diffusible signal factor (DSF) in Xanthomonas oryzae pv. oryzicola(Xoc)Rs105. METHODS: TheflgDxoc and flgExoc genes were amplified by PCR. We constructed deltaflgDxoc and deltaflgExoc, the deletion mutants from Rs105 by using double crossover method, and determined cell morphology, motility, pathogenicity in host rice and hypersensitive response (HR) in nonhost tobacco. We tested the differential expression of flgDxoc and flgExoc gene by reverse transcriptional polymerase chain reaction (RT-PCR) between the wide type and deltarpfFxoc (the deletion mutant of rpfFxoc gene, which could not produce DSF). RESULTS: We cloned flgDxoc and flgExoc from genomic DNA of Rs105. PCR and Southern blot analysis demonstrated that the flgDxoc and flgExoc genes were knocked out successfully. Both mutants were non-flagellated and significantly attenuated motility on the 0.3% semi-solid medium. The pathogenicity on rice were obviously attenuated in deltaflgDxoc and deltaflgExoc compared to the wild type. All the changes in mutant could be restored through the complementation. However, there was no significant difference in bacterial growth in MMX medium and induction of HR between mutant (deltaflgDxoc or deltaflgExoc) and the wild type. In addition, the results of RT-PCR demonstrated that the transcription level of flgDxoc and flgExoc were downregulated in deltarpfFxoc. CONCLUSION: This study showed that expressions of flgDxoc and flgExoc were positively regulated by DSF, and necessary for flagellar hook assembly and flagellar structure in Xoc. Meanwhile, FlgD and FlgE contributed to pathogen's virulence, motility and chemotaxis, but no differences at growth rate in MMX medium and HR in nonhost. In addition, our results provided molecular evidences that the contribution of DSF-type quorum sensing to pathogen's virulence might be, at least partially, dependent on bacterial flagellar in Xoc. PMID- 22043790 TI - [Characterization of the Rela/SpoT homologue slr1325 (syn-rsh) of the cyanobacterium Synechocystis sp. PCC6803]. AB - OBJECTIVE: Nucleotide guanosine-3', 5'-(bis) pyrophosphate (ppGpp) synthesized by (ppGpp) synthesase RelA or bifunctional ppGpp synthase/degradase RelA/SpoT, mediates bacterial stringent response to various stressful conditions. Here we characterized the slr1325 (syn-rsh) gene encoding a RelA/SpoT homolog (Syn-RSH) of the cyanobacterium Synechocystis sp. PCC6803. METHODS: We performed phenotypic complement test using Escherichia coli strain with(p) ppGpp-synthesis defect to determine Syn-RSH function(s), and employed chromatographic analysis of 32P labeled cellular mononucleotides to detect the accumulation of ppGpp in Escherichia coli strains expressing Syn-RSH and in Synechocystis sp. PCC6803. RESULTS: Syn-RSH expression in E. coli relA/spoT double mutant was able to restore the cell growth arrest; Chromatographic analysis of 32P-labeled cellular mononucleotides revealed that Syn-RSH expression resulted in the synthesis of ppGpp in E. coli strain with relA and spoT mutant mutation. Additionally, Synechocystis cells accumulated a low level of ppGpp under laboratory growth conditions. CONCLUSION: Syn-RSH possesses ppGpp synthase/degradase activities, and ppGpp is required for Synechocystis cell viability under normal growth conditions. PMID- 22043791 TI - [High efficient gene knockout in Verticillium dahliae]. AB - OBJECTIVE: We developed an efficient method of gene knockout in Verticillium dahliae, an important soil-borne fungal pathogen that causes cotton vascular wilt diseases. METHODS: By using fusion PCR, we constructed gene knockout vectors. By using Agrobacterium tumefaciens-mediated transformation and applying a herpes simplex virus thymidine kinase (HSVtk) gene in T-DNA as a conditional lethal gene to counter-select against ectopic transformants, we developed an efficient method to select gene knockout transformants. RESULTS: Gene knockout frequency for ADE4 and ChsV was 87% and 44% , respectively. CONCLUSION: We developed an efficient tool for gene knockout in Verticillium dahliae, which would help clarify the infection mechanism of this fungal pathogen. PMID- 22043792 TI - [Effect of controlled overexpression of xylulokinase by different promoters on xylose metabolism in Saccharomyces cerevisiae]. AB - OBJECTIVE: To investigate xylose metabolism in the Saccharomyces cerevisiae stains overexpressing the xylulokinase gene XKS1 at different levels by replacing the promoter in the chromosome. METHODS: Based on S. cerevisiae CEN. PK 113-5D, we constructed xylose-metabolizing strains where the promoter of xylulokinase gene XKS1 was replaced by TEF1 promoter, PGK1 promoter and HXK2 promoter on the chromosome. We quantitated the transcriptional level of XKS1 gene (accumulated mRNA) and measured the activity of xylulokinase in each stains. Furthermore, we also determined the intracellular level of ATP and evaluated the xylose fermenting abilities of the engineered strains. RESULTS: The engineered strains exhibited higher expression of xylulokinase than the parental strain at both transcription and enzyme activity levels. The highest xylulokinase activity was observed in the strain whose XKS1 was controlled by PGKlp, and was decreasingly followed by the strains whose XKS1 was controlled by TEF1p, HXK2p and native promoter. The expression level of xylulokinase negatively correlated with intracellular level of ATP and positively correlated with ability of ethanol production from xylose. The highest ethanol yield was 0.35 g/g consumed sugars while the lowest xylitol yield, which was 0.18 g/g consumed xylose, was observed. CONCLUSION: By promoter replacement, xylulokinase was overexpressed at different levels. In this work, higher expressional level of xylulokinase improved the conversion of xylose to ethanol. PMID- 22043793 TI - [Screening of high taxol producing fungi by mutagenesis and construction of subtracted cDNA library by suppression subtracted hybridization for differentially expressed genes]. AB - OBJECTIVE: To screen mutants with high yield of taxol, and construct cDNA subtractive library of obtained mutant and primary strain HD(1-3). METHODS: The spores of taxol-producing fungus HD(1-3) were treated by diethyl sulphate (DES), ultraviolet radiation and diethyl sulphate (UV + DES). cDNA subtractive library of taxol producing fungi from the mRNA of obtained mutant with high yield of taxol tester and HD(1-3) driver was constructed by using suppression subtracted hybridization (SSH). RESULTS: The optimal conditions for mutagenesis of strain HD(1-3) were as follows: the spore suspension was treated with 8% DES for 15 min, followed by UV irradiation (30 w, 30 cm distance) for 45 sec under magnetic stirring, a mutant UD(14-1) which was able to produce taxol with high yield and could be stably passed on genetics was found. Its ability to produce taxol was improved from 232.73 +/- 4.61 microg/L (strain HD(1-3)) to 312.81 +/- 7.51 microg/L (strain UD(14-1)). The tilter of the constructed cDNA library was 1.2 x 10(7) cfu/mL, the recombinant rate reached to 75.3% and the length of the inserted fragments was mostly 300 bp-1.0 kb. CONCLUSION: A mutant UD(14-11) with high yield was obtained, and cDNA subtractive library of the mutant UD(14-11) and strain HD(1-3) was constructed. The study laid solid foundation for isolation of taxol biosynthesis related genes and construction of engineering strains with high yield of taxol by genetic techniques. PMID- 22043794 TI - [Ribosome engineering of streptomyces sp. FJ3 from Three Gorges reservoir area and metabolic product of the selected mutant strain]. AB - OBJECTIVE: To explore new resource from inactive actinomycete strains, we screened resistant mutant strains by ribosome engineering, and analyzed the products derived from the selected mutant strains. METHODS: Three Gorges reservoir area-derived actinomycete strains including BD20, FJ3, WZ20 and FJ5 were used as initial strains, which showed no-antibacterial activities. The streptomycin-resistant (str(R)) mutants and rifampicin-resistant (rif(R)) mutants were screened by single colony isolation on streptomycin-containing plates and rifampicin-containing plates according to the method for obtaining drug-resistant mutants in ribosome engineering. The four initial strains and their str(R) mutants and rif(R)-mutants were fermented in a liquid medium with the same composition. Mutants with anti-Staphylococcus aureus activity were obtained by paper chromatography. The components of fermentation broth were analyzed by high performance liquid chromatography (HPLC) and high performance liquid chromatography-mass spectrometry (LC-MS). Furthermore, FJ3 strain was identified by 16S rDNA and morphology. RESULTS: The minimal inhibitory concentration (MIC) of streptomycin and rifampicin for FJ3 was: 0.5 microg/mL and 110 microg/mL, respectively. Twenty-four strR-mutant strains and 20 rif(R)-mutant strains of FJ3 mutant strains were selected for bioassay. The result of the antibacterial activity screening demonstrated that six strains inhibited bacteria. Two strains (FJ3-2 and FJ3-6) were screened from the streptomycin-resistance mutants of inactive strain FJ3. The result of bioassay showed that the fermentation broth of FJ3-2 and FJ3-6 exhibited obvious anti-Staphylococcus aureus activity. The assay of paper chromatography showed that the active substance may be nucleic acid class antibiotic via using solvent system Doskochilova. Moreover, the results of HPLC and LC-MS exhibited that this substance may be thiolutin. CONCLUSION: Ribosome engineering for changing the secondary metabolic function of the inactive wild-type actinomycete strains was a feasible method for the acquirement of active mutant strains, which will be beneficial to exploit the new medical actinomycete strains. PMID- 22043795 TI - [Mass spectrometry identification of secreted proteins from Bacillus firmus and analysis of its secretive sequences]. AB - OBJECTIVE: Bacillus firmus was a common probiotics bacteria in nature and widely used in the shrimp aquaculture. In order to construct expression vectors for secretive proteins, we identified several major secretive proteins of Bacillus firmus by mass spectrometry and analyzed their gene sequences to find signal peptide sequences. METHODS: The secreted proteins of Bacillus firmus were extracted and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The 3 highly expressed protein bands in the SDS-PAGE were identified by mass spectrometry Matrix Assisted Laser Desorption Ionization (MALDI)-Time of Flight (TOF)/Time of Flight (TOF) and the sequences were downloaded from National Center for Biotechnology Information (NCBI) database. Then Polymerase Chain Reaction (PCR) primers were designed according to the downloaded sequences and specific DNA bands were amplified sequenced and bioinformatics analyzed. RESULTS: The proteins were identified as the putative chitinase, enterotoxin A and protein BCG9842 of Bacillus firmus. Three signal peptides were conformed by using the online software SignaIP 3.0, namely bf-43, bf-37 and bf-16. The cellular localization of the secreted sequences were analyzed by PSORT. And we found that bf-43 located in the outer membrane of cells, bf-37 and bf-16 located in the extracellular cell. CONCLUSION: 3 major secreted proteins of Bacillus firmus have been identified. 3 possible signal peptides were obtained and will be useful for the construction of expression vectors for secretive proteins. PMID- 22043796 TI - [Homology modeling and molecular docking of xylitol dehydrogenase from Aspergillus Oryzae]. AB - OBJECTIVE: We investigated the structure model and function of xylitol dehydrogenase from Aspergillus oryzae. METHODS: Xylitol dehydrogenase (XDH) gene from Aspergillus oryzae was cloned and sequenced. We constructed four tertiary structure models of XDH by homology modeling with Swiss-MODEL and Modeller and obtained the best quality model by evaluation of PROCHECK and Prosa2003. The dockings of NAD+, Zn2+ and xylitol with XDH were performed by Molsoft program. RESULTS: Structure analysis suggested that XDH was a member of medium-chain dehydrogenase/reductase (MDR) family. This was supported by the presence of the zinc-containing alcohol dehydrogenase signature and a typical alcohol dehydrogenase Rossmann fold pattern composed by NAD+ binding domain present in MDR superfamily. The molecular docking indicated that amino acid residues Asp206, Arg211, Ser255, Ser301 and Arg303 in XDH binding domain had hydrogen bonding with NAD+, His72 and Glu73 in catalytic domain had hydrogen bonding with Zn2+, Ile46, Ile349, Lys350 and Thr351 in catalytic domain had hydrogen bonding with xylitol. CONCLUSION: These key amino acid residues might play a vital role in the XDH catalytic reaction and can instruct the further directed modification of XDH. PMID- 22043797 TI - [Binding of benzo(a)pyrene by Lactobacilli strains]. AB - OBJECTIVE: We studied the ability of Lactobacillus plantarum 121 and Lactobacillus pentosus ML32 to bind benzo(a)pyrene. METHODS: The percentage of benzo(a)pyrene bound by the lactobacilli strains was quantitated by HPLC after bacterial cells and benzo(a)pyrene were co-incubated in MRS media at 37 degrees C for 4 h. RESULTS: The percentage of benzo(a)pyrene-binding was 65.9% for 121 and 64.9% for ML32. Physical factors affecting binding ability included incubation time, temperature, bacterial cell viability, pH and concentrations of Ca2+ and Mg2+. Different chemical and enzymatic treatments to cells affected the binding of the two strains to benzo(a)pyrene. The simulation of gastrointestinal environments showed that the binding ability of the two strains depended largely upon pH and bile salt concentrations, but less upon treating time. Trypsin had only influence on the ability of 121 to bind benzo(a)pyrene. The presence of benzene in washing cell impaired the ability of the two strains to bind benzo(a)pyrene. CONCLUSIONS: Strains 121 and ML32 had potential to bind benzo(a)pyrene. PMID- 22043798 TI - [Antibody responses induced by mucosal DNA vaccine encoding the codon-optimized F protein of human respiratory syncytial virus (RSV) delivered with attenuated Salmonella typhimurium]. AB - OBJECTIVE: In order to investigate antibody responses by musosal DNA vaccines encoding the codon-optimized F protein of human respiratory syncytial virus (RSV) delivered with attenuated Salmonella typhimurium aroA strain SL7207 (SL7207) via intranasal or intragastric routes. METHODS: After the codon-optimized F gene was synthesized, we constructed eukaryotic expression plasmid pcDNA3.1/Fsyn and transformed it into SL7207 to get recombinant SL7207 of SL7207/pcDNA3.1/Fsyn. Then, SL7207/pcDNA3.1/Fsyn was exploited to evaluate its immunogenicity in BALB/c mice administered intranasally or intragastrically. The resultant serum and mucosal antibody responses were analyzed by indirect ELISA. RESULTS: Compared with intragastric immunization group, intranasal immunization group achieved higher level of RSV specific serum IgG and secretion IgA (SIgA) (P < 0.05). Moreover, F protein expressed by the codon-optimized F gene of Fsyn was of elevated immunogenicity, compared with wild type F (Fwt) (P < 0.05). CONCLUSION: Intranasal immunization and codon optimization approaches can improve antibody responses of RSV DNA vaccine delivered by attenuated Salmonella typhimurium aroA strain SL7207. PMID- 22043799 TI - [Distribution of putative virulence genes of avian pathogenic Escherichia coli IMT5155 in E. coli strains isolated from human and animal]. AB - OBJECTIVE: We investigated the distribution of autotransporter adhesin gene B11 and other putative virulence genes of APEC IMT5155, which contributed to study the pathogenic mechanism of Avian pathogenic Escherichia coli (APEC). METHODS: PCR and Dot blot were used to detect the distribution of putative virulence genes in E. coli strains isolated from different country (101 Chinese strains and 121 German strains), which were from different sources (human, avian and pig). The association of E. coli phylogenetic group and distribution of putative virulence genes was also analyzed. RESULTS: The putative virulence genes were most prevalent among APEC isolates, 36.4% (32/88) of APEC isolates harboring A1, 53.4% (47/88) for A8, 63.6% (56/88) for A10, 37.5% (33/88) for B11, 59.1% (52/88) for F3. The isolates positive for putative virulence genes were linked to E. coli phylogenetic group B2. Among Neonatal meningitis E. coli isolates, 60%, 80% and 80% were positive for putative virulence genes D1, E9 and F11, respectively. However, all the Neonatal meningitis E. coli strains were negative for B11. CONCLUSION: Autotransporter adhesin gene B11 and other putative virulence genes were associated to APEC. However, putative virulence genes D1, E9 and F11 were associated to Neonatal meningitis E. coli, which indicated that APEC might be a virulence gene reservoir for Neonatal meningitis E. coli. PMID- 22043800 TI - [Screening of optimal signal peptide for heterologous xylanase secretion by Bacillus subtilis]. AB - OBJECTIVE: We searched optimal signal peptide for heterologous and exogenous secretion of xylanase in Bacillus subtilis. METHODS: We constructed a screening vector for signal peptides from B. subtilis. The Alkali resistance xylanase gene (xynA) from Bacillus pumilus was chosen as reporter gene and cloned into E. coli and B. subtilis shuttle vector pGJ148 which has maltose-inducible promoter Pglv and spectinomycin resistant gene. 24 Sec-type signal peptides (SPs) was amplified from B. Subtilis 1A747 and cloned into the screening vector for the expression of xynA in B. Subtilis WB700. The xylanase activity of the culture supernatant were detected after 24h incubation. RESULTS: The screening of these signal peptides revealed differences in xylanase activity of the culture supernatants, The recombinant strain containing YnfF signal peptide showed the highest xylanase acitivity (37.2 IU/mL). CONCLUSION: Experiment proved screening of signal peptides is effective way for optimization of the export of heterologous protein in B. subtilis. PMID- 22043801 TI - [Stable expression of Mycobacterium tuberculosis protein EspB in RAW264.7]. AB - OBJECTIVE: We established a cell line stably expressing Mycobacterium tuberculosis secretory protein EspB in order to provide evidences for studying EspB in modulating the functions of macrophage. METHODS: The recombinant plasmid pEGFP-C1-EspB was first constructed, then RAW264.7 cell was transfected with pEGFP-C1-EspB and pEGFP-C1 by liposome respectively. After screening with a high level of G418, the macrophage cell lines that stably expressed EGFP-EspB fusion protein or EGFP were established. The gene and protein expression levels were further analyzed by RT-PCR, fluorescence microscopy and western blot. RESULTS: The EGFP-EspB fusion gene was integrated into the chromosome and the protein was stably expressed in the selected macrophage cell line. The macrophage cell lines that stably expressed EGFP-EspB fusion protein or EGFP were established. CONCLUSION: These results gave us a tool for the future study in the effects of EspB protein in modulating the functions of macrophage and its interaction with other molecules of macrophage. PMID- 22043802 TI - [Construction of a recombination plasmid labelled with green fluorescence and its application in Clonostachys rosea]. AB - OBJECTIVE: We constructed a recombinant eukaryotic expression vector harboring green fluorescent protein (GFP) and the hygromycin resistance gene hph, and observed its expression in Clonostachys rosea. METHODS: We used PCR, enzyme digestion, phosphorylation, ligation and transformation to construct the plasmid. Using protoplast preparation and transformation technologies, we expressed the plasmid in the fungi C. rosea. RESULTS: We created the eukaryotic expression vector, transformed it into C. rosea and observed green fluorescence with fluorescence microscope. CONCLUSION: The successful construction of the pANGH3 recombinant plasmid and its expression in C. rosea establishes a new model for studying fungal infection mechanisms. PMID- 22043804 TI - Apricot carotenoids possess potent anti-amyloidogenic activity in vitro. AB - Alzheimer's disease (AD) is the most common form of dementia and is characterized by the progressive accumulation of amyloid beta protein (Abeta) in areas of the brain. There has been an increased interest in screening for food-grade anti amyloidogenic compounds in foodstuffs. The purpose of this study was to screen and identify bioactive compounds with anti-amyloidogenicity in apricot fruits using synthetic Abeta(1-42). The anti-amyloidogenicity was investigated using thioflavin T fluorescence assay, electron microscopy, and dot blotting analysis. The carotenoid fraction from apricot showed strong inhibitory effects against oligomer and fibril formation of Abeta and fibril-destabilizing effects. Among the peaks in the HPLC chromatogram, lutein showed the strongest inhibitory effect on Abeta fibril formation. The inhibitory effect was dependent on the number and portion of hydroxyl groups on both sides of carotenoids. These findings suggest that lutein in fruits may be useful as a preventive agent for amyloid-associated diseases. PMID- 22043803 TI - Specific pathogen detection using bioorthogonal chemistry and diagnostic magnetic resonance. AB - The development of faster and more sensitive detection methods capable of identifying specific bacterial species and strains has remained a longstanding clinical challenge. Thus to date, the diagnosis of bacterial infections continues to rely on the performance of time-consuming microbiological cultures. Here, we demonstrate the use of bioorthogonal chemistry for magnetically labeling specific pathogens to enable their subsequent detection by nuclear magnetic resonance. Antibodies against a bacterial target of interest were first modified with trans cyclooctene and then coupled to tetrazine-modified magnetic nanoprobes, directly on the bacteria. This labeling method was verified by surface plasmon resonance as well as by highly specific detection of Staphylococcus aureus using a miniaturized diagnostic magnetic resonance system. Compared to other copper-free bioorthogonal chemistries, the cycloaddition reaction reported here displayed faster kinetics and yielded higher labeling efficiency. Considering the short assay times and the portability of the necessary instrumentation, it is feasible that this approach could be adapted for clinical use in resource-limited settings. PMID- 22043805 TI - Detection of extended-spectrum beta-lactamase in Enterobacter spp.--evaluation of six phenotypic tests. AB - Extended-spectrum beta-lactamases (ESBL) are plasmid-mediated enzymes that hydrolyze cephalosporins and monobactams. The lack of a standard method to detect ESBL in Enterobacter spp. has led to underestimating its frequency. The aim of this study was to evaluate ESBL detection in Enterobacter spp. By the double-disk synergy test (DDST) and combined disk test (CDT) assay using cefepime, cefotaxime, and ceftazime as substrates for ESBL, plus AmpC inhibitors in different associations. A total of 83 Enterobacter spp. ESBL and 31 non-ESBL Enterobacter spp. were tested, and a cutoff point >=3 mm was defined using a receiver operating characteristic (ROC) curve for combined disc methods. All tests showed 100% specificity. The sensitivity was 89.2% for DDST and CDT without AmpC inibitor, 90.4% in the combined disc test in Mueller-Hinton agar containing phenylboronic acid (CDT-PBAA), and 94% in the combined disc test in Mueller Hinton agar containing cloxacillin (CDT-CLXA). Cefepime was the best substrate, mainly when AmpC inhibitors were not used. However, superior results were achieved when all cephalosporins were evaluated together. In conclusion, to improve ESBL detection in Enterobacter spp., some modifications in phenotypic tests are needed, such as to reduce the distance between the discs to 20 mm in DDST, to use a cutoff point for >=3 mm on the CDT, and to include a cefepime disk or an inhibitor of AmpC in all tests. PMID- 22043806 TI - In vivo sequential selection of Escherichia coli with topoisomerase- and efflux mediated misleading quinolone resistance phenotypes. AB - Two mutants of Escherichia coli (V1 and V2) with acquired mechanisms of resistance to fluoroquinolones were isolated sequentially from blood cultures of a patient with cholangiocarcinoma treated repeatedly with ofloxacin; a third mutant (V3) was isolated under ciprofloxacin therapy. All mutants were related clonally. V1 was susceptible to quinolones but with diminished susceptibility to ofloxacin. V2 was hypersusceptible to nalidixic acid but had high-level resistance to ofloxacin. V3 was resistant to all quinolones. Ofloxacin selected for original gyrA and parC mutations, leading to the unusual and misleading resistance phenotypes of V1 and V2, whereas efflux played a major role in the increased resistance of V3. PMID- 22043807 TI - Efficient production and cellular characterization of sheep androgenetic embryos. AB - The production of androgenetic embryos in large animals is a complex procedure. Androgenetic embryos have been produced so far only in cattle and sheep using pronuclear transfer (PT) between zygotes derived from in vitro fertilization (IVF) of previously enucleated oocytes. PT is required due to the poor developmental potential of androgenotes derived from IVF of enucleated oocytes. Here we compare the developemt to blastocyst of androgenetic embryos produced by the standard pronuclear transfer and by fertilization of oocytes enucleated in Ca2+/Mg2+-free medium, without pronuclear transfer. The enucleation in Ca2+/Mg2+ free medium abolished almost completely the manipulation-induced activation, significantly improving the development to blastocyst of the androgenetic embryos (IVF followed by PT; 18.6%: IVF only; 17.7%, respectively). Karyotype analysis of IVF revealed a similar proportion of diploid embryos in androgenetic and control blastocysts (35% and 36%, respectively), although mixoploid blastocysts were frequently observed in both groups (64%). Androgenotes had lower total cell numbers than control and parthenogenetic embryos, but more cells in ICM cells comparing to parthenogenotes (30.42 vs. 17.15%). Higher expression of the pluripotency-associated gene NANOG, and trophoblastic-specific gene CDX2, were also observed in androgenotes compared to parthenogenotes and controls. The global methytion profile of androgenetic embryos was comparable to controls, but was lower than parthenogenetic embryos. The cell composition and methylation pattern we have detected in monoparental sheep monoparental embryos are unprecedented, and differ considerably from the standard reference mouse embryos. Altogether, these finding indicate significant differences across species in the molecular mechanisms regulating early development of monoparental embryos, and highlights the need to study postimplantation development of androgenetic embryos in sheep. PMID- 22043808 TI - Cell colony formation induced by Xenopus egg extract as a marker for improvement of cloned blastocyst formation in the pig. AB - Treatment with cytoplasmic extracts from Xenopus laevis eggs represents a potential tool for universal cellular reprogramming. However, the biochemical activity and quality of the extract vary from batch to batch. This study aimed to evaluate three different extract batches prepared by the same method based on the colony formation of cells after extract treatment, and subsequent in vitro cloning efficiency using treated cells as chromatin donors. Porcine fetal fibroblasts were treated with each batch of extract, and cultured in embryonic stem cell (ES) medium for 12 days. The number of forming colonies in treated cells was counted on Day 7 after extract treatment and significant variability was detected between different batches of extract. Similarly, when using cells from colonies at Days 7 to 8 after treatment for handmade cloning, increased blastocyst formation rates were observed after the cells were treated with a batch showing higher colony formation. In conclusion, assessment of cell colony formation may be used as selection marker for Xenopus egg extract used for pretreatment of donor cells prior to cloning. PMID- 22043809 TI - High performance weak donor-acceptor polymers in thin film transistors: effect of the acceptor on electronic properties, ambipolar conductivity, mobility, and thermal stability. AB - We have studied the electronic, physical, and transistor properties of a family of donor-acceptor polymers consisting of diketopyrrolopyrrole (DPP) coupled with different accepting companion units in order to determine the effects of donor acceptor interaction. Using the electronically neutral benzene (B), the weakly accepting benzothiadiazole (BT), and the strongly accepting benzobisthiadiazole (BBT), the accepting strength of the companion unit was systematically modulated. All polymers exhibited excellent transistor performance, with mobilities above 0.1 cm(2)V(-1)s(-1), even exceeding 1 cm(2)V(-1)s(-1) for one of the BBT containing polymers. We find that the BBT is the strongest acceptor, enabling the BBT-containing polymers to be strongly ambipolar. The BBT moiety also strengthens interchain interactions, which provides higher thermal stability and performance for transistors with BBT-containing polymers as the active layer. PMID- 22043810 TI - Magic acid free generation of antiaromatic dications at room temperature. AB - A new method for the generation of dicationic species via ionization of diols is described. The method makes use of milder reagents at room temperatures, an advantage over use of Magic Acid at -78 degrees C. A series of mono- and dications were synthesized successfully, including previously unattainable species. PMID- 22043811 TI - Photochemistry and photophysics of a Pd(II) metalloporphyrin: Re(I) tricarbonyl bipyridine molecular dyad and its activity toward the photoreduction of CO2 to CO. AB - The photochemistry and photophysics of the cationic molecular dyad, 5-{4 [rhenium(I)tricarbonylpicoline-4-methyl-2,2'-bipyridine-4'-carboxyamidyl]phenyl} 10,15,20-triphenylporphyrinatopalladium(II) ([Re(CO)(3)(Pic)Bpy-PdTPP][PF(6)]) have been investigated. The single crystal X-ray structure for the thiocyanate analogue, [Re(CO)(3)(NCS)Bpy-PdTPP], exhibits torsion angles of 69.1(9) degrees , 178.1(7) degrees , and 156.8(9) degrees between porphyrin plane, porphyrin linked C(6)H(4) group, amide moiety, and Bpy, respectively. Steady-state photoexcitation (lambda(ex) = 520 nm) of [Re(CO)(3)(Pic)Bpy-PdTPP][PF(6)] in dimethylformamide (DMF) results in substitution of Pic by bromide at the Re(I)Bpy core. When [Re(CO)(3)(Pic)Bpy-PdTPP][PF(6)] is employed as a photocatalyst for the reduction of CO(2) to CO in DMF/NEt(3) solution with lambda(ex) > 420 nm, 2 turnovers (TNs) CO are formed after 4 h. If instead, a two-component mixture of PdTPP sensitizer and mononuclear [Re(CO)(3)(Pic)Bpy][PF(6)] catalyst is used, 3 TNs CO are formed. In each experiment however, CO only forms after a slight induction period and during the concurrent photoreduction of the sensitizer to a Pd(II) chlorin species. Palladium(II) meso-tetraphenylchlorin, the hydrogenated porphyrin analogue of PdTPP, has been synthesized independently and can be substituted for PdTPP in the two-component system with [Re(CO)(3)(Pic)Bpy][PF(6)], forming 9 TNs CO. An intramolecular electron transfer process for the dyad is supported by cyclic voltammetry and steady-state emission studies, from which the free energy change was calculated to be DeltaG(ox)* = 0.08 eV. Electron transfer from Pd(II) porphyrin to Re(I) tricarbonyl bipyridine in [Re(CO)(3)(Pic)Bpy-PdTPP][PF(6)] was monitored using time-resolved infrared (TRIR) spectroscopy in the nu(CO) region on several time scales with excitation at 532 nm. Spectra were recorded in CH(2)Cl(2) with and without NEt(3). Picosecond TRIR spectroscopy shows rapid growth of bands assigned to the pi-pi* excited state (2029 cm(-1)) and to the charge-separated state (2008, 1908 cm( 1)); these bands decay and the parent recovers with lifetimes of 20-50 ps. Spectra recorded on longer time scales (ns, MUs, and seconds) show the growth and decay of further species with nu(CO) bands indicative of electron transfer to Re(Bpy). PMID- 22043813 TI - Introducing a novel method to assess cumulative steroid concentrations: increased hair cortisol concentrations over 6 months in medicated patients with depression. AB - Depression has been linked to increased cortisol concentrations using point measures taken from urine, blood, or saliva samples. However, with regard to hypercortisolism-induced consequences, long-term cumulative cortisol burden is of relevance. Our objective was to use hair analysis as a new method to assess cortisol exposure over 6 months in depressed patients and healthy controls. We examined 23 depressed patients (8 men and 15 women, mean age: 41.6 years ( +/- standard deviation (SD), 13.1 years); mean duration of current depressive episode 9 months ( +/- SD, 13 months)) and 64 healthy controls, matched for age and gender. Cortisol concentrations in two 3-cm hair segments from near to the scalp were analyzed, representing cortisol secretion during the 6 months prior to sampling. Compared with healthy individuals, depressed patients had higher hair cortisol concentrations in the first (mean +/- SD: 26.7 +/- 20.8 vs. 18.7 +/- 11.5 pg/mg, p < 0.05) and second hair segment (mean +/- SD: 21.9 +/- 23.7 vs. 13.4 +/- 9.6 pg/mg, p < 0.05). In conclusion, hair cortisol analysis confirmed enhanced cortisol secretion in depressed patients over a prolonged time period. Because of the retrospective and cumulative nature of cortisol in hair, the assessment of hair cortisol concentration may help in addressing unanswered questions regarding hypothalamic-pituitary-adrenal axis overactivity and associated health consequences in psychiatric disorders. PMID- 22043814 TI - Nickel hexacyanoferrate nanoparticle electrodes for aqueous sodium and potassium ion batteries. AB - The electrical power grid faces a growing need for large-scale energy storage over a wide range of time scales due to costly short-term transients, frequency regulation, and load balancing. The durability, high power, energy efficiency, and low cost needed for grid-scale storage pose substantial challenges for conventional battery technology. (1, 2) Here, we demonstrate insertion/extraction of sodium and potassium ions in a low-strain nickel hexacyanoferrate electrode material for at least five thousand deep cycles at high current densities in inexpensive aqueous electrolytes. Its open-framework structure allows retention of 66% of the initial capacity even at a very high (41.7C) rate. At low current densities, its round trip energy efficiency reaches 99%. This low-cost material is readily synthesized in bulk quantities. The long cycle life, high power, good energy efficiency, safety, and inexpensive production method make nickel hexacyanoferrate an attractive candidate for use in large-scale batteries to support the electrical grid. PMID- 22043815 TI - How federal health-care policies interface with urban and rural areas: a comparison of three systems. AB - Global public health policies span national borders and affect multitudes of people. The spread of infectious disease has neither political nor economic boundaries, and when elevated to a status of pandemic proportions, immediate action is required. In federal systems of government, the national level leads the policy formation and implementation process, but also collaborates with supranational organisations as part of the global health network. Likewise, the national level of government cooperates with sub-national governments located in both urban and rural areas. Rural areas, particularly in less developed countries, tend to have higher poverty rates and lack the benefits of proper medical facilities, communication modes and technology to prevent the spread of disease. From the perspective of epidemiological surveillance and intervention, this article will examine federal health policies in three federal systems: Australia, Malaysia and the USA. Using the theoretical foundations of collaborative federalism, this article specifically examines how collaborative arrangements and interactions among governmental and non-governmental actors help to address the inherent discrepancies that exist between policy implementation and reactions to outbreaks in urban and rural areas. This is considered in the context of the recent H1N1 influenza pandemic, which spread significantly across the globe in 2009 and is now in what has been termed the 'post-pandemic era'. PMID- 22043816 TI - Prevention of paraquat-induced apoptosis in human neuronal SH-SY5Y cells by lipocalin-type prostaglandin D synthase. AB - Paraquat is a widely used herbicide that is structurally similar to the known dopaminergic neurotoxicant 1-methyl-4-phenyl-pyridine and acts as a potential etiologic factor for the development of Parkinson's disease. In this study, we investigated the protective roles of lipocalin-type prostaglandin (PG) D synthase (L-PGDS) against paraquat-mediated apoptosis of human neuronal SH-SY5Y cells. The treatment of SH-SY5Y cells with paraquat decreased the intracellular GSH level, and enhanced the cell death with elevation of the caspase activities. L-PGDS was expressed in SH-SY5Y cells, and its expression was enhanced with the peak at 2 h after the initiation of the treatment with paraquat. Inhibition of PGD2 synthesis and exogenously added PGs showed no effects regarding the paraquat-mediated apoptosis. SiRNA-mediated suppression of L-PGDS expression in the paraquat treated cells increased the cell death and caspase activities. Moreover, over expression of L-PGDS suppressed the cell death and caspase activities in the paraquat-treated cells. The results of a promoter-luciferase assay demonstrated that paraquat-mediated elevation of L-PGDS gene expression occurred through the NF-kappaB element in the proximal promoter region of the L-PGDS gene in SH-SY5Y cells. These results indicate that L-PGDS protected against the apoptosis in the paraquat-treated SH-SY5Y cells through the up-regulation of L-PGDS expression via the NF-kappaB element. Thus, L-PGDS might potentially serve as an agent for prevention of human neurodegenerative diseases caused by oxidative stress and apoptosis. PMID- 22043817 TI - Milk stimulates growth of prostate cancer cells in culture. AB - Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes. PMID- 22043818 TI - Toll-like receptor-mediated inhibition of Gas6 and ProS expression facilitates inflammatory cytokine production in mouse macrophages. AB - Activation of Toll-like receptors (TLRs) triggers rapid inflammatory cytokine production in various cell types. The exogenous product of growth-arrest-specific gene 6 (Gas6) and Protein S (ProS) inhibit the TLR-triggered inflammatory responses through the activation of Tyro3, Axl and Mer (TAM) receptors. However, regulation of the Gas6/ProS-TAM system remains largely unknown. In the current study, mouse macrophages are shown to constitutively express Gas6 and ProS, which synergistically suppress the basal and TLR-triggered production of inflammatory cytokines, including those of tumour necrosis factor-alpha, interleukin-6 and interleukin-1beta, by the macrophages in an autocrine manner. Notably, TLR signalling markedly decreases Gas6 and ProS expression in macrophages through the activation of the nuclear factor-kappaB. Further, the down-regulation of Gas6 and ProS by TLR signalling facilitates the TLR-mediated inflammatory cytokine production in mouse macrophages. These results describe a self-regulatory mechanism of TLR signalling through the suppression of Gas6 and ProS expression. PMID- 22043819 TI - Symptom burden and quality of life in patients with malignant fungating wounds. AB - AIM: This study describes the relationship between symptoms and quality of life in patients with malignant fungating wounds. BACKGROUND: Malignant fungating wounds are complex wounds that can bleed, become malodorous due to infection and are painful causing physical and psychological distress. However, there is a lack of literature on the impact that such wounds can have on quality of life. METHODS: This was a descriptive, cross-sectional multi-centre study of patients with malignant fungating wounds. Participants were recruited from the palliative care, hospice, outpatient clinic and oncology units of three medical centres in Taiwan. Data were collected from February 2008 to August 2009. A structured questionnaire obtained socio-demographic information, medical details, wound assessment information and the Taiwanese version of the McGill quality of life questionnaire was administered by interview. RESULTS: McGill quality of life scores indicated that the participants had the lowest quality of life. The participant's age, dressing change frequency, pain, wound dressing comfort, wound symptom, bleeding and malodour had statistically significant negative correlations with quality of life. Multiple regression analysis showed that age, malodour, pain issues and psychological issues explained 87% of the total variance in quality of life. CONCLUSION: This study contributes to our understanding of the impact of malignant fungating wounds and how correct assessment and management is necessary to improve quality of life. Educational intervention research is needed for patients and caregivers in countries where this has not yet been performed. Further research should also identify whether nursing competence has a direct impact on quality of life. PMID- 22043820 TI - Direct cholangioscopy-based holmium laser lithotripsy of difficult bile duct stones by using an ultrathin upper endoscope without a separate biliary irrigating catheter. AB - OBJECTIVE: We investigated the impact of direct peroral cholangioscopy (POC) based holmium laser lithotripsy using an ultrathin endoscope with direct irrigation via a 2-mm-diameter working channel to remove difficult common bile duct (CBD) stones without a separate biliary catheter. BACKGROUND DATA: Few clinical studies have reported the successful removal of difficult CBD stones by direct POC-based laser lithotripsy using an ultrathin upper endoscope. Previous studies used a separate biliary catheter to ensure continuous irrigation. METHODS: Ten patients (6 males; mean age 63.3 years) with difficult CBD stones who were not amenable to conventional endoscopic procedures were examined. Direct POC using an ultrathin upper endoscope was performed in all patients. Holmium laser lithotripsy with direct saline irrigation via the operating channel of an ultrathin endoscope was performed until stone fragments were captured in a basket. RESULTS: The overall success rate of bile duct clearance was 90% (9 of 10 patients) and the mean number of treatment sessions was 1.2 (range, 1-2). Mechanical lithotripsy was performed to complete stone removal in one patient (10%) who had a distal CBD stricture. One patient experienced mild cholangitis following laser lithotripsy. CONCLUSIONS: Holmium laser lithotripsy under direct POC using an ultrathin upper endoscope may be an effective and safe technique for removal of difficult CBD stones. Direct irrigation via the 2-mm-diameter working channel of the ultrathin endoscope provides sufficient fluid medium and affords good endoscopic viewing to assure stone fragmentation without any need for a separate biliary catheter. PMID- 22043821 TI - Photodynamic therapy with indocyanine green injection and near-infrared light irradiation has phototoxic effects and delays paralysis in spinal metastasis. AB - OBJECTIVE: The purpose of this study was to investigate the phototoxic effects of photodynamic therapy (PDT) with indocyanine green (ICG) and near-infrared light irradiation on rat mammary adenocarcinoma cells, and its therapeutic efficacy in a rat model of spinal metastasis. BACKGROUND DATA: Although PDT has been successfully used as a non-radiation treatment for many malignancies, it has not yet been clinically applied for treating spinal metastasis. METHODS: For the phototoxicity study, CRL-1666 cells were treated with PDT and cell viability was measured by WST-1 assay. For the efficacy study, 26 female Fischer 344 rats with spinal metastasis in the L6 vertebra were divided into three treatment groups: PDT with local injection of ICG (9 rats), PDT with systemic injection of ICG (10 rats), and no treatment or control (7 rats). Both the PDT groups received near infrared light irradiation with a total energy of 10 J (1 W for 10 sec). The light was delivered directly through a single silica probe which was set on the left side of the L6 vertebral body. Hindlimb motor function was monitored according to the Basso-Beattie-Bresnahan (BBB) scale. Further, the observation periods were calculated to determine the survival time. RESULTS: The PDT exerted immediate and persistent phototoxic effects. Furthermore, the PDT with local injection of ICG as well as systemic injection of ICG delayed the deterioration of paralysis and prolonged the observation period. CONCLUSIONS: PDT with ICG injection and near-infrared light irradiation could be an effective local adjuvant treatment for spinal metastasis. PMID- 22043822 TI - Evolution of the protein corona of lipid gene vectors as a function of plasma concentration. AB - The concept that the effective unit of interest in the cell-nanomaterial interaction is the particle and its corona of associated proteins is emerging. Here we investigate the compositional evolution of the protein corona of 1,2 dioleoyl-3-trimethylammonium propane (DOTAP) cationic liposomes (CLs) and DOTAP/DNA lipoplexes over a wide range of plasma concentrations (2.5-80%). The composition of the hard corona of lipoplexes is quite stable, but that of CLs does evolve considerably. We show that the protein corona of CLs is made of both low-affinity and competitive-binding proteins whose relative abundance changes with the plasma concentration. This result may have deep biological implications for the application of lipid-based gene vectors both in vitro and in vivo. PMID- 22043823 TI - Effects of surface charge and Gibbs surface energy on the settlement behaviour of barnacle cyprids (Balanus amphitrite). AB - Gibbs surface energy has long been considered to be an important parameter in the design of fouling-resistant surfaces for marine applications. Rigorous testing of the hypothesis that settlement is related to Gibbs surface energy however has never been accomplished, due mainly to practical limitations imposed by the necessary combination of surface engineering and biological evaluation methods. In this article, the effects of surface charge and Gibbs surface energy on the settlement of cyprids of an important fouling barnacle, Balanus amphitrite, were evaluated. Settlement assays were conducted on a range of self-assembled monolayers (SAMs) (CH(3)-, OH-, COOH-, N(CH(3))(3) (+)-, NH(2)-terminated), presented in gold-coated polystyrene well plates, varying in terms of their surface charge and Gibbs surface energy. Contrary to contemporary theory, settlement was not increased by high-energy surfaces, rather the opposite was found to be the case with cyprids settling in greater numbers on a low-energy CH(3)- SAM compared to a high-energy OH- SAM. Settlement was also greater on negatively-charged SAMs, compared to neutral and positively-charged SAMs. These findings are discussed in the context of data drawn from surfaces that varied in multiple characteristics simultaneously, as have been used previously for such experiments. The finding that surface charge, rather than total surface energy, may be responsible for surface selection by cyprids, will have significant implications for the design of future fouling-resistant materials. PMID- 22043824 TI - Robust immune response elicited by a novel and unique Mycobacterium tuberculosis protein using an optimized DNA/protein heterologous prime/boost protocol. AB - An efficacious tuberculosis (TB) vaccine will probably need to induce both CD4 and CD8 T-cell responses specific to a protective Mycobacterium tuberculosis antigen(s). To achieve this broad cellular immune response we tested a heterologous DNA/protein combination vaccine strategy. We used a purified recombinant protein preparation of a unique M. tuberculosis antigen (rMT1721) found in the urine of TB patients, an optimized plasmid DNA expressing this protein (DNA-MT1721), and a Toll-like receptor 4 agonist adjuvant. We found that priming mice with DNA-MT1721 and subsequently boosting with rMT1721 elicited high titres of specific IgG1 and IgG2a antibodies as well as high magnitude and polyfunctional CD4(+) T-cell responses. However, no detectable CD8(+) T-cell response was observed using this regimen of immunization. In contrast, both CD4(+) and CD8(+) T-cell responses were detected after a prime/boost vaccination regimen using rMT1721 as the priming antigen and DNA-MT1721 as the boosting immunogen. These findings support the exploration of heterologous DNA/protein immunization strategies in vaccine development against TB and possibly other infectious diseases. PMID- 22043825 TI - In vitro properties of platelets stored in three different additive solutions. AB - BACKGROUND: New platelet (PLT) additive solutions (PASs) contain compounds that might improve the storage conditions for PLTs. This study compares the in vitro function, including hemostatic properties (clot formation and elasticity), of PLTs in T-Sol, Composol, or SSP+ during storage for 5 days. STUDY DESIGN AND METHODS: Fifteen buffy coats were pooled and divided into three parts. PLT concentrates (PCs) with 30% plasma and 70% PAS (T-Sol, Composol, or SSP+) were prepared (n = 10). Swirling, PLT count, blood gases, metabolic variables, PLT activation markers, and coagulation by free oscillation rheometry (FOR) were analyzed on Days 1 and 5. RESULTS: Swirling was well preserved and pH acceptable (6.4-7.4) during storage for all PASs. Storage of PLTs in T-Sol led to a decrease in PLT count whereas the number of PLTs was unchanged in Composol or SSP+ PCs. PLTs in T-Sol showed higher glucose metabolism than PLTs in Composol or in SSP+. At the end of storage PLTs in T-Sol had higher spontaneous activation and lower ability to respond to an agonist than PLTs in Composol or SSP+. PLTs in all the PASs had a similar ability to promote clot formation and clot elasticity. CONCLUSION: Storage of PLTs in Composol or in SSP+ improved the quality of PCs in terms of better maintained PLT count, lower glucose metabolism, lower spontaneous activation, and improved response to a PLT agonist compared to PLTs in T-Sol. PLTs stored in the various PASs had similar hemostatic properties. These findings make Composol and SSP+ interesting alternatives as PASs. PMID- 22043826 TI - Effects of different extraction buffers on peanut protein detectability and lateral flow device (LFD) performance. AB - The accidental uptake of peanuts can cause severe health reactions in allergic individuals. Reliable determination of traces of peanuts in food products is required to support correct labelling and therefore minimise consumers' risk. The immunoanalytical detectability of potentially allergenic peanut proteins is dependent on previous heat treatment, the extraction capacity of the applied buffer and the specificity of the antibody. In this study a lateral flow device (LFD) for the detection of peanut protein was developed and the capacity of 30 different buffers to extract proteins from mildly and strongly roasted peanut samples as well as their influence on the test strip performance were investigated. Most of the tested buffers showed good extraction capacity for putative Ara h 1 from mildly roasted peanuts. Protein extraction from dark roasted samples required denaturing additives, which were proven to be incompatible with LFD performance. High-pH buffers increased the protein yield but inhibited signal generation on the test strip. Overall, the best results were achieved using neutral phosphate buffers but equal detectability of differently altered proteins due to food processing cannot be assured yet for immunoanalytical methods. PMID- 22043827 TI - Statins as potential treatment for cholesterol gallstones: an attempt to understand the underlying mechanism of actions. AB - INTRODUCTION: Statin therapy is widely used across the globe for the treatment and prevention of cardiovascular disease (CVD). It is well established that statin therapy is associated with significant decreases in low-density lipoprotein cholesterol (LDL-C) and plasma cholesterol levels. Cholesterol gallstones are a common problem, resulting in hospital admission and surgery, throughout western healthcare systems. AREAS COVERED: This review describes the mechanisms, and addresses the potential, for statins to be used as a treatment for gallstones. Medline was searched for the risk factors and treatment of cholesterol gallstones. EXPERT OPINION: Obesity, metabolic syndrome, non alcoholic fatty liver disease (NAFLD), insulin resistance and high-fat diets (unsaturated fats) rich in cholesterol are all associated risk factors for cholesterol gallstones. In view of the high prevalence of cholesterol gallstones, there is an urgent need to understand whether pharmacological therapies can be harnessed for the treatment of cholesterol gallstones. Gallstones are shown to be associated with an increased risk, not only of mortality, but also of CVD. Statins, widely used in prevention of CVD and hypercholesteremia, have been shown to dissolve cholesterol gallstones in animal models and human studies, highlighting the potential for a pharmacological therapy for gallstones. More studies are required to understand the role of statins in the treatment of gallstones and for comparison with current treatment strategies. PMID- 22043828 TI - Detecting nuclear materials smuggling: performance evaluation of container inspection policies. AB - In recent years, the United States, along with many other countries, has significantly increased its detection and defense mechanisms against terrorist attacks. A potential attack with a nuclear weapon, using nuclear materials smuggled into the country, has been identified as a particularly grave threat. The system for detecting illicit nuclear materials that is currently in place at U.S. ports of entry relies heavily on passive radiation detectors and a risk scoring approach using the automated targeting system (ATS). In this article we analyze this existing inspection system and demonstrate its performance for several smuggling scenarios. We provide evidence that the current inspection system is inherently incapable of reliably detecting sophisticated smuggling attempts that use small quantities of well-shielded nuclear material. To counter the weaknesses of the current ATS-based inspection system, we propose two new inspection systems: the hardness control system (HCS) and the hybrid inspection system (HYB). The HCS uses radiography information to classify incoming containers based on their cargo content into "hard" or "soft" containers, which then go through different inspection treatment. The HYB combines the radiography information with the intelligence information from the ATS. We compare and contrast the relative performance of these two new inspection systems with the existing ATS-based system. Our studies indicate that the HCS and HYB policies outperform the ATS-based policy for a wide range of realistic smuggling scenarios. We also examine the impact of changes in adversary behavior on the new inspection systems and find that they effectively preclude strategic gaming behavior of the adversary. PMID- 22043830 TI - Transvaginal ultrasonography of rectosigmoid endometriosis: interobserver variation of lesion size. AB - This study evaluates the interobserver variation of transvaginal ultrasonographic measurements of the size of deep infiltrating endometriosis lesions in the rectosigmoid wall performed by an experienced and a less experienced sonographer. Fifteen outpatient women were seen for a gynecologic examination and 24 women were seen with rectosigmoid endometriosis. Transvaginal ultrasonography was performed independently by two observers with a focus on the presence and size of rectosigmoid endometriosis. The senior observer had several years of experience, whereas the junior observer was a medical student with no prior experience in transvaginal ultrasonography. The findings of the two observers were identical concerning the identification of rectosigmoid endometriosis. The probability of differences in size within 30% of the mean was 0.81, 0.63 and 0.61 for length, width and depth, respectively. Our data suggest that fair skills in this technique can be acquired by inexperienced examiners within a short period of time. PMID- 22043831 TI - Effect of molecular weight on the adsorption characteristics of lignosulfonates. AB - Sequentially adsorbed multilayers composed of sodium lignosulfonate (SL) and poly(diallyldimethylammonium chloride) (PDAC) were built up by a layer-by-layer self-assembly technique to investigate the adsorption characteristics of SL microgels for sensitivity improvement. The effect of molecular weight on the adsorption characteristics was investigated by light scattering, UV-visible spectroscopy, ellipsometer, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and contact angle measurements. Results show that the self assembly of SL microgels and PDAC is not mainly driven by electrostatic interaction but by cation-pi interaction and hydrophobic interaction. The Coulomb interaction in SL microgels causes a "slow mode" peak in dynamic light scattering measurement, but it can be completely suppressed when SL is dissolved in 1.2 mol/L NaCl solutions due to charge-screening. The SL in 1.2 mol/L NaCl solutions can be well adsorbed on a PDAC surface, indicating that the electrostatic interaction is not the main driving force. The presence of cation-pi interaction between SL and PDAC is detected by a stoichiometric ratio of SL to PDAC in SL/PDAC self-assembled films. During SL/PDAC self-assembly, hydrophobic interaction plays an important role in determining the adsorption rate, film thickness, surface morphology, and surface properties. SL with a higher M(w) has a stronger hydrophobic ability in water, so it exhibits a slower adsorption rate, a larger film thickness, and a higher film roughness. SL with different M(w) has almost the same wettability because of a larger hydrophobic effect that increases contact angle and a higher film roughness that decreases contact angle. In this case, the opposite effects cancel each other to make no difference in wettability, but it still reflects the role of the hydrophobic effect in surface properties. PMID- 22043829 TI - The regulation and role of T follicular helper cells in immunity. AB - It is well established that the generation of a high-affinity long-lived antibody response requires the presence of T cells, specifically CD4+ T cells. These CD4+ T cells support the generation of a germinal centre (GC) response where somatic hypermutation and affinity maturation take place leading to the generation of memory B cells and plasma cells, which provide long-lasting protection. Greater insight into the nature of the CD4+ T cells involved in this process was provided by two studies in 2000 that described CD4+ T cells residing in the B cell follicle that expressed CXCR5. As a result these cells were named follicular B helper T cells, now more commonly known as T follicular helper (Tfh) cells. Since then there has been enormous growth in our understanding of these cells, now considered a distinct T helper (Th) cell lineage that can arise from naive CD4+ T cells following activation. This review summarizes some of the most recent work that has characterized Tfh cells and the pathways that lead to their generation. PMID- 22043832 TI - The force applied to successfully turn a foetus during reattempts of external cephalic version is substantially reduced when performed under spinal analgesia. AB - OBJECTIVE: To compare the forces exerted during external cephalic version (ECV) on the maternal abdomen between ( 1 ) the primary attempts performed without spinal analgesia (SA), which failed and ( 2 ) the subsequent reattempts performed under SA. METHODS: Patients with an uncomplicated singleton breech-presenting pregnancy suitable for ECV were recruited. During ECV, the operator wore a pair of gloves, which had thin piezo-resistive pressure sensors measuring the contact pressure between the operator's hands and maternal abdomen. For patients who had failed ECV, reattempts by the same operator was made with patients under SA, and the applied force was measured in the same manner. The profile of the exerted forces over time during each attempt was analyzed and denoted by pressure-time integral (PTI: mmHg sec). Pain score was also graded by patients using visual analogue scale. Both PTI and pain score before and after the use of SA were then compared. RESULTS: Overall, eight patients who had a failed ECV without SA underwent a reattempt with SA. All of them had successful version and the median PTI of the successful attempts under SA were lower than that of the previous failed attempts performed without SA (127 386 mmHg sec vs. 298,424 mmHg sec; p = 0.017). All of them also reported a 0 pain score, which was significantly lower than that of before (median 7.5; p = 0.016). CONCLUSIONS: SA improves the success rate of ECV as well as reduces the force required for successful version. PMID- 22043833 TI - Effect of freeze-dried berries on the development of reflux-induced esophageal adenocarcinoma. AB - The incidence of esophageal adenocarcinoma in humans is increasing more rapidly than any other malignancy in the United States. Animal studies have demonstrated the efficacy of freeze-dried berry supplementation on carcinogen-induced esophageal squamous cell carcinoma in rats; however, no such studies have been done in esophagoduodenal anastomosis (EDA), an animal model for reflux-induced esophageal adenocarcinoma (EAC) development. Eight-week-old male Sprague-Dawley rats were randomized into 3 groups: EDA + control diet (EDA-CD; n = 10); EDA + 2.5% black raspberry diet (EDA-BRB; n = 11) and EDA + 2.5% blueberry diet (EDA BB; n = 12). After 2 wk of feeding the respective diets, the rats underwent EDA surgery to induce gastroesophageal reflux and then continued the diet. Measurement of feed intake suggested that all EDA-operated animals had lower feed intake starting at 10 wk after surgery and this was significant close to termination at 24 wk. There were no significant differences in either reflux esophagitis (RE), intestinal metaplasia (IM) (70% in CD, 64% in BRB, and 66% in BB; P = 0.1) or EAC incidence (30% for CD, 34% for BRB, and 25% for BB; P = 0.2) with supplementation. Berry diets did not alter COX-2 levels, but BB diet significantly reduced MnSOD levels (1.23 +/- 0.2) compared to control diet (2.05 +/- 0.14; P < 0.05). We conclude that a dietary supplementation of freeze-dried BRB and BB at 2.5% (w/w) was not effective in the prevention of reflux-induced esophageal adenocarcinoma in this EDA animal model. PMID- 22043835 TI - Differential hepatic gene expression in the broiler chicken in response to the combined stressors of food withdrawal, catching and transport at the end of production. AB - Broiler (meat) chickens experience the combined acute stressors of food withdrawal, catching and transport (FCT) prior to slaughter as part of normal commercial practice at the end of their lives. This has associated physiological consequences, potentially affecting both welfare and meat quality, some of which are mediated through altered hepatic function. This study compared global hepatic gene expression between control birds and those exposed to commercial FCT using 20K chicken oligonucleotide microarrays. In response to FCT, 733 genes were differentially expressed of which 486 could be mapped onto the genome. The principal molecular and cellular functions thus affected by FCT involved lipid and carbohydrate metabolism with a suppression of mRNA expression for genes involved in lipogenesis, glycolysis and glycogenolysis and an induction of those involved in gluconeogenesis, fatty acid metabolism and ketone synthesis. There was also significant differential expression of genes associated with cellular control and immune function. These stressful events associated with FCT in commercial broiler chickens altered expression of hepatic genes associated with energy metabolism, with exhaustion of stored hepatic and pectoral muscle glycogen. A better understanding of FCT-induced stress through the use of gene expression arrays may in future inform husbandry practices, to improve both welfare and meat quality. PMID- 22043836 TI - If only I had taken my usual route...: age-related differences in counter-factual thinking. AB - Previous research suggests that young adults can shift between rational and experiential modes of thinking when forming social judgments. The present study examines whether older adults demonstrate this flexibility in thinking. Young and older adults completed an If-only task adapted from Epstein, Lipson, and Huh's (1992 , Journal of Personality and Social Psychology, 62, 328) examination of individuals' ability to adopt rational or experiential modes of thought while making a judgment about characters who experience a negative event that could have been avoided. Consistent with our expectations for their judgments of the characters, young adults shifted between experiential and rational modes of thought when instructed to do so. Conversely, regardless of the mode of thought being used or the order with which they adopted the different modes of thought (i.e., shifting from experiential to rational in Study 1 and from rational to experiential in Study 2), older adults consistently offered judgments and justifications that reflected a preference for experiential-based thought. PMID- 22043837 TI - Acceptability and feasibility of integration of HIV care services into antenatal clinics in rural Kenya: a qualitative provider interview study. AB - The aim of this study was to explore the perspectives of healthcare providers on the advantages and disadvantages of integrating HIV care services, including highly active antiretroviral therapy (HAART), into antenatal care (ANC) clinics in rural Kenya. We conducted a qualitative study using in-depth interviews and thematic analysis; 36 healthcare providers from six health centres in Nyanza Province, Kenya participated. Effects on service providers included increased workload due to the incorporation of specialised HIV services into ANC clinics. Providers observed that integration results in decreased patient time spent at the health facility, increased efficiency and closer provider-patient relationships; all leading to increased patient satisfaction. Providers also said that women would be more likely to receive HAART and adhere to their treatment as a result of improved confidentiality and decreased stigma. However, a minority of providers noted that integration could result in longer appointment times for HIV positive women at ANC clinics leading to inadvertent disclosure. Integration could lead to strengthened ANC, postpartum care, prevention of mother-to-child transmission and HIV care for women and their families. However, integration efforts need to take into account potential negative effects on ANC provider workload, disclosure and the quality of care. PMID- 22043838 TI - Quantification of allyl hexanoate in pineapple beverages and yogurts as a case study to characterise a source of uncertainty in dietary exposure assessment to flavouring substances. AB - One source of uncertainty in the estimation of dietary exposure to flavouring substances is the uncertainty in the occurrence and concentration levels of these substances naturally present or added to foodstuffs. The aim of this study was to assess the variability of concentration levels of allyl hexanoate, considered as a case study, in two main food categories to which it is often added: pineapple juice-based beverages and yogurts containing pineapple. Thirty-four beverages and 29 yogurts, with pineapple fruit or juice and added flavourings declared as ingredients on the package, were purchased from the local market (in Rome) and analysed. Analytical methods based on the stir bar sorptive extraction (SBSE) technique for the isolation of the target analyte, and on GC-MS analysis for final determination, were developed for the two food categories. In beverages, allyl hexanoate concentrations ranged from less than 0.01 to 16.71 mg l(-1), whereas in yogurts they ranged from 0.02 to 89.41 mg kg(-1). Average concentrations in beverages and yogurts with pineapple as the main fruit ingredient (1.91 mg l(-1) for beverages, 9.61 mg kg(-1) for yogurts) were in fair agreement with average use level data reported from industry surveys for the relevant food categories (4.5 and 6.0 mg kg(-1), respectively). Within the group of yogurts a single product was found to contain a level of allyl hexanoate more than 10-fold higher than the average reported use level. The screening techniques developed by the European Food Safety Authority (EFSA) using use level data provided by industry gave estimates of exposure that were of the same order of magnitude as the estimates obtained for regular consumers who would be loyal to the pineapple yogurt and beverage products containing the highest observed concentration of the substance of interest. In this specific case the uncertainty in the results obtained with the use of standard screening techniques for exposure assessment based on industry reported use levels is low. PMID- 22043839 TI - Managing the combination of nonalcoholic fatty liver disease and metabolic syndrome. AB - INTRODUCTION: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are part of the same metabolic defect, both having insulin resistance as the main pathogenic mechanism and sharing similar outcomes (i.e., cardiovascular and liver-related mortality). The prevalence of NAFLD is expected to rise, owing to the increasing worldwide prevalence of obesity and MetS; therefore, the identification of factors responsible for disease progression is essential to devise therapeutic strategies. AREAS COVERED: The available and potential future treatments for NAFLD in combination with MetS are reviewed in this paper, following an extensive literature search and personal experience. EXPERT OPINION: All NAFLD patients should be evaluated for their metabolic, cardiovascular and liver-related risk. Weight loss through lifestyle intervention remains the most comprehensive and safe treatment of NAFLD and associated MetS; however, > 50% of patients fail to achieve target weight loss. Pharmacologic treatment seems to be important for these patients and for NAFLD cases with more advanced liver disease. It temporarily reverses metabolic alterations, but liver disease progresses after the treatment is stopped. Although current treatments are unsatisfactory, new drugs have been proposed and a few innovative compounds are in the pipeline of pharmaceutical companies. Before pharmacologic treatment can be routinely recommended for NAFLD, long-term randomized trials are needed, along with assessments of the safety and benefits of drugs on proper histological outcomes or validated surrogate markers. The intensive control of individual features of MetS remains mandatory. PMID- 22043840 TI - Regional and temporal variation in hysterectomy rates and surgical routes for benign diseases in the Netherlands. AB - OBJECTIVE: To provide descriptive statistics on hysterectomy for benign gynecological conditions in the Netherlands and to analyze regional and temporal variations in hysterectomy rates and surgical routes. DESIGN: Retrospective cohort study. SETTING: Dutch hospitals. POPULATION: All women with a hysterectomy for benign gynecological conditions in the Netherlands in 1995-2005. METHODS: This study is based on an analysis of the Dutch registry of hospital admissions for 1995-2005. MAIN OUTCOME MEASURES: The age-adjusted hysterectomy rate and age- and diagnosis-adjusted proportion of vaginal hysterectomies for each Dutch healthcare region and time period. RESULTS: The average annual crude hysterectomy rate for benign disease only, was 17.2 per 10,000 women of all ages. The vaginal route was chosen for 50.8% of the patients. During the study period, the number of hysterectomies for bleeding disorders declined almost 25%. Among 27 Dutch healthcare regions, the age-adjusted hysterectomy rates for bleeding disorders and pelvic organ prolapse varied 2.2- and 2.3-fold, respectively. The average annual age- and diagnosis-adjusted proportion of vaginal hysterectomies varied from 43.4 to 63.8%. The regional differences with regard to rate and proportion declined slightly over time. CONCLUSIONS: The Netherlands is among the countries with the lowest hysterectomy rates and the highest proportion of vaginal hysterectomies. The regional differences indicate that a further decrease in the hysterectomy rates and an increase in the proportion of vaginal hysterectomies are possible. PMID- 22043841 TI - Comments on the article titled 'Component mode synthesis approach to estimate tibial strains in gait', Journal of Medical Engineering & Technology, 33, pp. 488 495, 2009. PMID- 22043843 TI - Modality effect in false recognition: evidence from Chinese characters. AB - Using the Deese/Roediger-McDermott (DRM) false memory method, Smith and Hunt ( 1998 ) first reported the modality effect on false memory and showed that false recall from DRM lists was lower following visual study than following auditory study, which led to numerous studies on the mechanism of modality effect on false memory and provided many competing explanations. In the present experiment, the authors tested the modality effect in false recognition by using a blocked presentation condition and a random presentation condition. The present experiment found a modality effect different from the results of the previous research; namely, false recognition was shown to be greater following visual study than following auditory study, especially in the blocked presentation condition rather than in the random presentation condition. The authors argued that this reversed modality effect may be due to different encoding and processing characteristics between Chinese characters and English words. Compared with English words, visual graphemes of critical lures in Chinese lists are likely to be activated and encoded in participants' minds, thus it is more difficult for participants to discriminate later inner graphemes from those items presented in visual modality. Hence visual presentation could lead to more false recognition than auditory presentation in Chinese lists. The results in the present experiment demonstrated that semantic activation occurring during the encoding and retrieve phases played an important role in modality effect in false recognition, and our findings might be explained by the activation-monitoring account. Utilisant la methode de fausse memoire de Deese/Roediger-McDermott (DRM), Smith et Hunt ( 1998 ) ont d'abord rendu compte de l'effet de modalite sur la fausse memoire et ils ont montre que le faux rappel a partir des listes de DRM etait plus faible suivant une etude visuelle plutot qu'une etude auditive. Ceci a mene a plusieurs etudes sur le mecanisme de l'effet de modalite sur la fausse memoire, lesquelles ont fourni plusieurs explications concurrentes. Dans la presente experience, les auteurs ont teste l'effet de modalite dans la fausse reconnaissance en utilisant une condition de presentation fixe et une condition de presentation aleatoire. Cette experience a revele un effet de modalite different des resultats obtenus dans les recherches anterieures. En effet, la fausse reconnaissance etait plus elevee suivant une etude visuelle plutot qu'une etude auditive, specialement dans la condition de presentation fixe. Les auteurs suggerent que cet effet de modalite inverse peut etre du a des caracteristiques d'encodage et de processus differentes entre les caracteres chinois et les mots anglais. Comparativement aux mots anglais, les graphemes visuels des leurres critiques dans les listes chinoises sont susceptibles d'etre actives et encodes dans l'esprit des participants, rendant plus difficile de discriminer les graphemes interiorises plus tard de ces items presentes dans la modalite visuelle. Ainsi, la presentation visuelle pourrait mener a davantage de fausse reconnaissance que la presentation auditive dans les listes chinoises. Les resultats de la presente experience ont demontre que l'activation semantique se produisait durant l'encodage et que la phase de retrait jouait un role important dans l'effet de modalite dans la fausse reconnaissance. Nos resultats peuvent etre expliques par la theorie activation-controle. Utilizando el metodo de Deese/Roediger-McDermott (DRM) de falsa mamoria, Smith y Hunt ( 1998 ) fueron los primeros en encontrar el efecto de modalidad en la falsa memoria y demostraron que los falsos recuerdos del listado DRM fueron mas bajos despues de un estudio visual que despues de un estudio auditivo lo cual llevo a varios estudios sobre el mecanismo del efecto de la modalidad sobre falsos recuerdos y proporciono varias explicaciones que compiten entre si. En el presente trabajo, los autores estudiaron el efecto de la modalidad en el falso reconocimiento utilizando una condicion de presentacion en bloques y otra condicion de presentacion de forma aleatoria. El presente experimento encontro un efecto de la modalidad diferente de los resultados de los estudios anteriores. En concreto, el reconocimiento falso ha resultado ser mayor despues del estudio visual que despues del estudio auditivo, especialmente en caso de la presentacion en bloques en comparacion con la condicion de presentacion aleatoria. Los autores argumentan que este efecto inverso de la modalidad puede ser causado por diferentes caracteristicas de codificacion y procesamiento entre caracteres chinos y palabras inglesas. En comparacion con las palabras inglesas, los grafemas visuales de las palabras criticas en chino tienen probabilidad de ser activadas y codificadas en las mentes de los participantes, por tanto, es mas dificil discriminar posteriores grafemas internos de los que fueron presentados en la modalidad visual. Por tanto, la presentacion visual podria conducir a mas falsos reconocimientos que la presentacion auditiva en los listados de palabras chinas. Los resultados del presente experimento demostraron que la activacion semantica durante las fases de codificacion y recuperacion jugo un rol importante en el efecto de falso reconocimiento segun modalidad y que nuestros resultados se pueden explicar teniendo en cuenta la activacion y la vigilancia. PMID- 22043844 TI - Social orientations and adolescent health behaviours in Hungary. AB - Adolescent health behaviours are influenced by a variety of social factors, including social orientations, such as social comparison or competitiveness. The main goal of the present study was to investigate the role that these social orientations might play in health behaviours (both health-impairing and health promoting). Data were collected from high school students (N = 548; ages 14-20 years; 39.9% males) in two counties of the Southern Plain Region of Hungary. The self-administered questionnaires contained items on sociodemographics, such as age, sex, parental schooling, and socioeconomic status (SES) self-assessment; school achievement, health behaviours, competitiveness and social comparison. Multiple regression analyses suggest that those who scored higher on competitiveness engaged in more substance use, a pattern that was not present for health-promoting behaviours. Social comparison, however, was associated with lower levels of substance use. In addition, in relation to health-impairing behaviours, both competitiveness and social comparison interacted with sex; both social orientation variables proved to be more important for boys. Social comparison also contributed to health-promoting behaviours among boys. Findings support the idea that the role of social orientations, such as competitiveness and social comparison, can be quite different depending on sex and the nature of the health behaviour. While competitiveness may act as a risk factor for substance use among boys, social comparison may act as a protection. It appears that social orientations play less of a role in girls' health-related behaviours. More focus is needed on gender differences in influences on adolescents' health related behaviours. Les comportements de sante des adolescents sont influences par une variete de facteurs sociaux, incluant les orientations sociales telles que la comparaison sociale ou la competitivite. Le but principal de la presente etude etait d'examiner le role que ces orientations sociales peuvent jouer dans les comportements de sante (a la fois nefastes et benefiques). Les donnees ont ete recueillies aupres d'etudiants collegiaux (N = 548; ages de 14 a 20 ans; 39.9% masculins) dans deux comtes du sud de la Hongrie. Les questionnaires auto administres contenaient des items portant sur les aspects sociodemographiques (tels que l'age, le sexe, la scolarite des parents et le niveau economique), la performance scolaire, les comportements de sante, la competitivite et la comparaison sociale. Des analyses de regression multiple suggerent que ceux qui ont obtenu des scores superieurs de competitivite consommaient plus de substances, un patron qui n'etait pas present pour les comportements de sante benefiques. La comparaison sociale, cependant, etait associee a de faibles niveaux de consommation de substances. De plus, en relation avec les comportements de sante nefastes, a la fois la competitivite et la comparaison sociale interagissaient avec le sexe; les deux variables d'orientation sociale se sont revelees etre plus importantes pour les garcons. La comparaison sociale contribuait aussi aux comportements de sante benefiques chez les garcons. Ces resultats soutiennent l'idee que le role des orientations sociales, telles que la competitivite et la comparaison sociale, peut etre assez different dependamment du sexe de l'individu et de la nature du comportement de sante. Tandis que la competitivite peut agir comme facteur de risque pour la consommation de substances chez les garcons, la comparaison sociale peut agir comme facteur de protection. Il apparait que les orientations sociales jouent un role moins grand en ce qui concerne les comportements de sante des filles. Il est necessaire de focaliser davantage sur les differences de genre dans les influences reliees aux comportements de sante des adolescents. Las conductas de salud en adolescentes son influenciadas por una variedad de factores sociales, incluyendo las orientaciones sociales, la comparacion social, asi como la capacidad de competencia. La meta principal de este estudio fue el investigar el rol que pueden jugar estas orientaciones sociales sobre las conductas de salud (tanto perjudiciales como promotoras de salud). Los datos fueron obtenidos en escolares de la escuela secundaria (N = 548; edad 14-20 anos; 39.9 por ciento hombres) en dos provincias de la zona sur de Hungria. Los cuestionarios autoadministrados incluyen preguntas sobre datos socio-demograficos como edad, sexo, nivel educativo de los padres y autoevaluacion del estatus socio-economico; logros academicos, conductas de salud, competitividad y comparacion social. Los analisis de regresion multiple sugieren que aquellos participantes con altos puntajes en la capacidad de competencia estaban mas comprometidos con el uso de substancias, un patron que no esta considerado dentro de las conductas de promocion de la salud. Por otro lado la comparacion social estuvo asociada con bajos niveles de uso de substancias. Adicionalmente en relacion a las conductas perjudiciales para la salud, tanto la competitividad como la comparacion social interactuaban con el sexo. Se pudo observar que ambas variables de la orientacion social eran mas importantes para los muchachos. La comparacion social tambien contribuye con las conductas promotoras de salud entre los muchachos. Estos descubrimientos apoyan la idea de que el rol de las orientaciones sociales, como la competitividad y la comparacion social, pueden actuar de manera diferente, dependiendo del sexo y de la naturaleza de la conducta de salud. Mientras que competitividad puede actuar como un factor de riesgo respecto del uso de substancias entre muchachos, la comparacion social puede actuar como una factor protectivo. Aparentemente las orientaciones sociales juegan un rol menos importante en las conductas de salud de las muchachas. Por ello se necesita una mayor focalizacion respecto de la influencia de las diferencias de genero sobre las conductas asociadas con la salud en adolescentes. PMID- 22043845 TI - Adult attachment styles and cognitive vulnerability to depression in a sample of undergraduate students: the mediational roles of sociotropy and autonomy. AB - We analysed the mediational role of the personality dimensions of sociotropy and autonomy in the relationship between certain styles of attachment and depressive symptoms. In order for us to do so, a group of university students filled out the Beck Depression Inventory (BDI), the Revised Personal Style Inventory (PSI-II) and the Relationship Questionnaire (RQ). Individuals having attachment styles with a negative model of self (preoccupied and fearful) obtained significantly higher scores in the BDI than those having attachment styles with a positive model of self (secure and dismissing), which coincides with previous research. We followed the standard procedure of Baron and Kenny of linear regression in order to perform the mediational analyses. The preoccupied attachment style-depressive symptoms relationship was mediated by sociotropy. It was also found that autonomy exerted a significant mediational effect on the relationship between the fearful attachment style and depressive symptoms. These results are consistent with the notion that insecure attachment predisposes individuals to the development of depressogenic personality styles. Thus, the findings of the present study contribute to improving the understanding of the factors involved in the development of vulnerability to depression. Furthermore, the results point out the importance of evaluating both attachment style and sociotropy/autonomy personality dimensions for the treatment of depressive patients. PMID- 22043846 TI - Speaking, writing, and memory span in children: output modality affects cognitive performance. AB - Low-level processes of children's written language production are cognitively more costly than those involved in speaking. This has been shown by French authors who compared oral and written memory span performance. The observed difficulties of children's, but not of adults' low-level processes in writing may stem from graphomotoric as well as from orthographic inadequacies. We report on five experiments designed to replicate and expand the original results. First, the French results were successfully replicated for German third-graders, and for university students. Then, the developmental changes of the cognitive costs of writing were examined during primary school, comparing the performance of second- and fourth-graders. Next, we show that unpractised writing modes, which were experimentally induced, also lead to a decrease of memory performance in adults, which supports the assumption that a lack of graphomotoric automation is responsible for the observed effects in children. However, unpractised handwriting yields clearer results than unpractised typing. Lastly, we try to separate the influences of graphomotoric as opposed to orthographic difficulties by having the words composed through pointing on a "spelling board". This attempt, however, has not been successful, probably because the pointing to letters introduced other low-level costs. In sum, throughout the four years of primary school, German children show worse memory span performance in writing compared to oral recall, with an overall increase in both modalities. Thus, writing had not fully caught up with speaking regarding the implied cognitive costs by the end of primary school. Therefore, conclusions relate to the question of how to assess properly any kind of knowledge and abilities through language production. Los procesos de bajo nivel en la produccion de lenguaje escrito en ninos son mas costosos a nivel cognitivo que los que estan implicados en el habla. Esto ha sido demostrado por autores franceses quienes compararon la ejecucion en la capacidad de retencion en la memoria oral y escrita. Las dificultades observadas en ninos, pero no en adultos, en procesos de bajo nivel en la escritura pueden derivarse de la inadecuacion grafomotriz u ortografica. Informamos sobre cinco experimentos disenados para replicar y ampliar los resultados originales. Primero, los resultados franceses fueron replicados con exito para alemanes en tercer curso y para estudiantes universitarios. Despues, los cambios evolutivos en costes cognitivos en la escritura fueron estudiados durante la educacion primaria, comparando la ejecucion de los alumnos del segundo y cuarto curso. Posteriormente, demostramos que las formas de escribir no practicadas, que se han inducido experimentalmente, conducen a la disminucion de la ejecucion en la memoria tambien en adultos, lo cual apoya la hipotesis de que la falta de la automatizacion grafomotriz es la responsable de los efectos encontrados en ninos. Sin embargo, la escritura a mano muestra resultados mas claros que la escritura a maquina. Por ultimo, hemos intentado separar la influencia de la grafomotricidad frente a las dificultades ortograficas componiendo las palabras senalando en una "pizarra de ortografia". Este intento, sin embargo, no ha tenido exito, probablemente porque senalar letras ha introducido otros costes de bajo nivel. Resumiendo, a lo largo de los cuatro anos de la educacion primaria, los ninos alemanes muestran peor ejecucion en retencion en memoria en la escritura, en comparacion con el recuerdo oral, con un incremento general en ambas modalidades. Por tanto, al final de la educacion primaria, la escritura no ha igualado todavia el habla en cuanto a los costes cognitivos. Por consiguiente, las conclusiones estan relacionadas con la cuestion de como evaluar cualquier tipo de conocimiento o habilidades mediante la produccion de lenguaje. Les processus de bas niveau de la production du langage ecrit chez les enfants sont cognitivement plus couteux que ceux impliques dans le langage parle. Ceci a ete demontre par des auteurs francais qui ont compare la performance de l'etendue de la memoire orale et ecrite. L'observation de difficultes dans les processus de bas niveau dans l'ecriture chez les enfants, et non chez les adultes, pourrait etre due aux inadequations graphomotoriques et orthographiques. Nous rapportons cinq experimentations dont le but etait de repliquer et d'elargir les resultats originaux. Premierement, les resultats francais ont ete repliques avec succes pour les eleves allemands de troisieme annee et pour les etudiants universitaires. Ensuite, les changements developpmentaux des couts cognitifs de l'ecriture ont ete examines a l'ecole primaire en comparant la performance des eleves de deuxieme et de quatrieme annees. Par la suite, nous avons montre que les modes d'ecriture non pratiques qui etaient experimentalement induits indiquent une diminution de la performance de la memoire, chez les adults aussi, ce qui supporte la supposition qu'un manque d'automatisme graphomotorique est responsable des effets observes chez les enfants. Cependant, une ecriture a la main sans entrainement mene a des resultats plus claires que la dactylographie sans entrainement. Enfin, nous avons tente de separer les influences des difficultes graphomotoriques versus difficultes orthographiques a travers la composition des mots en les indiquant sur un tableau d'ortographe. Cependant, cette tentative n'a pas reussi, probablement a cause du fait d'indiquer les lettres presente d'autres couts dont le niveau est bas. En resume, a travers les quatre annees de l'ecole primaire, les enfants allemands montrent une pire performance de l'etendue de memoire dans l'ecriture, en comparaison au rappel oral, avec une augmentation globale dans les deux modalites. Ainsi, toujours a la fin de l'ecole primaire, l'ecriture n'a pas rattrape l'expression orale en ce qui concerne les couts cognitifs implicites. Par consequent, les conclusions se rapportent a la question de comment evaluer correctement n'importe quel type de connaissances et d'habiletes a travers la production du langage. PMID- 22043847 TI - Vertical perceptual span and the processing of visual signals in reading. AB - A previous study by Pollatsek et al. ( 1993 ) claims that the perceptual span in reading is restricted to the fixated line, i.e. readers typically focus their visual attention on the line of text being read. The present study investigated whether readers make use of content structure signals (paragraph indentations and topic headings) present several lines away from the currently fixated line. We reasoned that as these signals are low-resolution visual objects (as opposed to letter and word identity), readers may attend to them even if they are located some distance away from the fixated line. Participants read a hierarchically organized multi-topic expository text containing structure signals in either a normal condition or a window condition, where the text disappeared above and below a vertical 3 degrees gaze-contingent region. After reading, participants were asked to produce a written recall of the text. The results showed that the overall reading rate was not affected by the window. Nevertheless, the headings were reread more in the normal condition than in the window one. In addition, more topics were recalled in the normal than in the window condition. We interpret the results as indicating that the readers visually attend to useful text layout features while considering bigger units than single text lines. The perception of topic headings located away from the fixated line may favour long range regressions towards them, which in turn may favour text comprehension. This claim is consistent with previous studies that showed that look-back fixations to headings are performed with an integrative intent. PMID- 22043848 TI - Effects of country size and language similarity on international attitudes: a six nation study. AB - Linguistically similar neighbouring nations that differ in size are often asymmetrical in their attitudinal relations towards each other: Citizens of smaller nations tend to see larger nations as less likeable and less similar than vice versa. We hypothesized that the smaller nations' reaction is the consequence of a threatened identity due to its relative size combined with too much similarity on a vital part of its identity, namely language. To test this hypothesis, 832 high-school students from six different ethnic/national entities (France, Germany, Austria, the French- and German-speaking parts of Switzerland, the French- and Dutch-speaking parts of Belgium, and The Netherlands) completed a questionnaire on liking and similarity ratings. The results-to a large extent showed that differences in size, in combination with linguistic similarity with another nation, pose a threat to the identity of the smaller nation or ethnic group. Differences in size, in combination with linguistic similarity, were associated with asymmetries in mutual liking on one hand and asymmetrical perceptions of similarity to the other country on the other hand. The conclusions of this study are consistent with findings of earlier research and stress the importance of language for a nation's identity. Moreover, the findings support social identity theory as a useful theory for understanding intergroup and international relations. Les nations voisines linguistiquement similaires qui different en taille sont souvent asymetriques dans leurs relations attitudinales l'une envers l'autre: les citoyens des nations plus petites tendent a voir les nations plus grandes comme moins sympathiques et moins semblables et vice-versa. Notre hypothese etait que la reaction des nations plus petites est la consequence d'un sentiment de menace a l'identite du a leur taille reduite combinee avec trop de similitudes concernant une partie vitale de leur identite: c'est-a-dire le langage. Pour tester cette hypothese, 832 etudiants collegiaux issus de six ethnies/nationalites differentes (la France, l'Allemagne, l'Autriche, la Suisse romande et allemande, la Belgique francaise et neerlandaise, les Pays-Bas) ont complete un questionnaire sur les taux de sympathie et de similitude. Les resultats ont indique que les differences en taille en combinaison avec la similitude linguistique avec une autre nation representent une menace pour l'identite de la nation ou du groupe ethnique plus petit. Les differences en taille en combinaison avec la similitude linguistique etaient associees, d'une part, avec des asymetries dans la sympathie mutuelle et, d'autre part, avec des perceptions asymetriques de similitude avec l'autre nation. Les conclusions de cette etude sont en accord avec les resultats des etudes anterieures et soutiennent l'importance du langage pour l'identite d'une nation. De plus, les resultats appuient l'utilite de la theorie de l'identite sociale pour comprendre les relations intergroupes et internationales. Naciones vecinas con similitudes linguisticas pero que difieren en tamano son frecuentemente asimetricas respecto de sus relaciones actitudinales una respecto de la otra. Los cuidadanos de naciones pequenas tienden a ver a naciones mas grandes como menos simpaticas y parecidas que viceversa. Nosotros hipotetizamos que la reaccion de las naciones mas pequenas es la consequencia de una identidad amenazada debido a su menor tamano combinada con una similitud muy grande relacionada con una parte vital de su identidad: es decir el lenguaje. Para probar esta hipotesis 832 alumnos de la escuela secundaria de seis diferentes grupos etnicos/nacionales (Francia, Alemania, Austria, regiones en Suiza en las que se habla frances y aleman, regiones en Belgica en las que se habla frances y holandes asi como los Paises Bajos) completaron un cuestionario sobre gustos y similitudes. Los resultados mostraron - en alto grado - que las diferencias en el tamano en combinacion con las similitudes linguisticas con otras naciones, se asocian con la amenaza de la identidad de las naciones o grupos etnicos mas pequenos. Las diferencias en tamano en combinacion con las similitudes linguisticas estuvieron asociadas con asimetrias repecto del aprecio mutuo por un lado, asi como por otro lado, con percepciones asimetricas de similitud con el otro pais. Las conclusiones de este estudio son consistentes con los descubrimientos de estudios previos y recalcan la importancia del lenguaje en la identidad de una nacion. Adicionalmente estos resultados soportan la Teoria de la Identidad Social como una teoria util en la comprension de las relaciones entre grupos asi como a nivel de las relaciones internacionales. PMID- 22043849 TI - Dispositional optimism among American and Jordanian college students: are Westerners really more upbeat than Easterners? AB - The present study aimed at assessing some previous research conclusions, based primarily on comparisons of North Americans and East Asians, that Westerners tend to be optimistic while Easterners tend to be pessimistic. Two samples of European American and Jordanian college students were administered a questionnaire consisting of items measuring dispositional optimism along with items pertaining to risk and self-protective behaviors (e.g., seatbelt use, vehicular speeding, smoking) and social and demographic factors (e.g., sex, socioeconomic status, religiosity). The findings uncovered dispositional optimism to be stronger for American compared to Jordanian participants. Separate analyses of optimism versus pessimism revealed that Jordanian participants were more pessimistic, but not less optimistic than their American counterparts. No significant correlations were found between dispositional optimism and sex, socioeconomic status, or religiosity. The levels of optimism displayed by Jordanians in this study are inconsistent with previous claims of an optimistic West and a pessimistic East, and suggest that self-enhancing processes may not be confined to Western or highly individualistic groups. The findings did not uncover an association between dispositional optimism and risk or self-protective behaviors. Multiple regression analyses showed cultural background and sex to be the best predictors of these behaviors. The implications of these findings are discussed. La presente etude avait pour but d'evaluer quelques conclusions de recherches passees, fondees principalement sur des comparaisons de nord-americains et d'asiatiques de l'est, indiquant que les occidentaux tendent a etre optimistes alors que les orientaux tendent a etre pessimistes. Deux echantillons d'etudiants americains-europeens et jordaniens du college ont rempli un questionnaire ayant des items mesurant l'optimisme dispositionnel avec d'autres items qui portent sur les comportements de risque et d'auto-protection (e.g., la ceinture de securite, la vitesse au volant, l'usage de tabac), sur les facteurs sociaux et demographiques (e.g., le sexe, le statut socio-economique, la religiosite). Les resultats ont indique que l'optimisme dispositionnel etait plus fort chez les americains en comparaison aux participants jordaniens. Des analyses separees de l'optimisme versus le pessimisme ont montre que les participants jordaniens n'etaient pas pessimistes mais pas moins optimistes que leurs homologues americains. Il n'y avait pas de correlations significatives entre l'optimisme dispotionnel et le sexe, le statut socio-economique et la religiosite. Les niveaux d'optimisme dispotionnel affiches par les jordaniens dans cette etude sont inconsistents avec les affirmations passees d'un occident optimiste et d'un orient pessimiste et suggerent que les processus d'auto-amelioration pourraient ne pas etre restreints aux occidentaux ou aux groupes hautement individualistes. Les resultats n'ont pas devoile une association entre l'optimise dispotionnel et les comportements de risque ou les comportements d'auto-protection. Des analyses de regression multiples ont indique que le contexte culturel et le sexe sont les meilleurs predicteurs de ces comportements. Les implications de ces resultats sont discutees. El presente estudio se baso en la evaluacion de algunas conclusiones de investigaciones anteriores, basadas principalmente en comparaciones de habitantes de norteamericanos con habitantes del Asia del este, en las que se proponia que mientras los occidentales tienden a ser optimistas, los orientales tienden a ser pesimistas. En dos muestras de estudiantes de la escuela superior europeo-americanos y jordanos se administro un cuestionario que consiste en preguntas que miden el optimismo disposicional junto con preguntas que evaluan conductas de riesgo y de autoproteccion (p.e., uso de cinturon de seguridad, velocidad de manejo, fumar) asi como factores sociales y demograficos (p.e., sexualidad, estatus socioeconomico, religiosidad). Las conclusiones senalaron que el optimismo disposicional es mas fuerte en los participantes americanos en comparacion con los jordanos. Analisis separados del optimismo en relacion con el pesimismo revelaron que los participantes jordanos eran mas pesimistas, pero no menos optimistas que sus homologos americanos. No se encontraron correlaciones significativas entre optimismo disposicional y sexualidad, estatus socioeconomico o religiosidad. El nivel de optimismo mostrado por los jordanos en este estudio es inconsistente con las propuestas anteriores de un Oeste optimista y un Este pesimista, y sugiere que los procesos de autodesarrollo no pueden ser limitados a grupos Occidentales o altamente individualistas. Las resultados no mostraron una asociacion entre optimismo disposicional y conductas de riesgo o autoprotectoras. Los analisis de regresion multiples mostraron que el contexto cultural y la sexualidad son los mejores predictores de estas conductas. Las implicaciones de estos hallazgos fueron discutidas. PMID- 22043850 TI - Emotional and behavioural reactions to moral transgressions: cross-cultural and individual variations in India and Britain. AB - Reactions to moral transgressions are subject to influence at both the cultural and individual levels. Transgressions against an individual's rights or against social conventions of hierarchy may elicit different reactions in individualistic and collectivistic cultures. In the current study, affective and behavioural reactions to transgressions of autonomy (rights) and community (hierarchy) were examined in India and Britain. Results revealed that although reactions to autonomy transgressions are similar in India and Britain, Indian participants express more moral outrage than do Britons in response to transgressions of community. Results also supported the contention of emotion-specificity in affective moral reaction: Participants in both India and Britain reported anger in response to autonomy transgressions, but contempt in response to violations of community. Importantly, these results extend previous research by demonstrating the importance of emotion specificity in moral reactions, as opposed to categorization or dilemma resolution. In addition, an individual difference measure of respect for persons was shown to moderate reactions to moral transgressions. Specifically, participants with high respect for persons were less negative to violators of the community ethic, but not the autonomy ethic. These findings highlight the importance of examining emotion-specific responses in the moral domain and introduce a significant individual difference variable, respect for persons, into the psychology of morality. Les reactions aux transgressions morales sont susceptibles d'influence a la fois aux niveaux culturel et individuel. Les transgressions contre les droits d'un individu ou contre les conventions sociales d'hierarchie peuvent susciter de differentes reactions dans les cultures individualiste et collectiviste. Dans la presente etude, les reactions affective et comportementale aux transgressions de l'autonomie (droits) et de la communaute (hierachie) ont ete examinees en Inde et en Grande-Bretagne. Les resultats ont indique que, malgre la similitude des reactions aux transgressions de l'autonomie en Inde et en Grande-Bretagne, les participants indiens ont exprime plus d'indignation morale que les britanniques en reponse aux transgressions de la communaute. Les resultats ont egalement appuye la controverse de la specifite de l'emotion dans la relation morale affective: les participants a la fois en Inde et en Grande-Bretagne ont rapporte de la colere en reponse aux transgressions de l'autonomie mais du mepris en reponse aux transgressions de la communaute. De facon importante, ces resultats ont elargi la recherche passee en demontrant l'importance de la specificite de l'emotion dans les reactions morales, contrairement a la categorisation ou a la solution du dilemme. En plus, il a ete demontre qu'une mesure des differences individuelles du respect envers les personnes a modere les reactions aux transgressions morales. Specifiquement, les participants ayant un grand respect envers les personnes ont ete moins negatifs envers les violateurs de l'ethique de la communaute mais pas de l'ethique de l'autonomie. Ces resultats soulignent l'importance d'examiner les reponses specifique a l'emotion dans le domaine moral et introduisent une variable des differences individuelles, soit le respect envers les personnes, dans la psychologie de la moralite. Las reacciones a las transgresiones morales estan sujetas a la influencia a niveles culturales e individuales. Las transgresiones contra los derechos individuales o convenciones sociales de jerarquias pueden provocar distintas reacciones en las culturas individualistas y colectivistas. En el presente estudio, se examinaron las reacciones afectivas y conductuales a las transgresiones contra la autonomia (derechos) y comunidad (jerarquia) en la India y en Gran Bretana. Los resultados demostraron que, aunque las reacciones a las transgresiones contra la autonomia fueran parecidas en la India y en Gran Bretana, los participantes indios expresaron mas indignacion moral que los britanicos en la respuesta a la transgresion contra la comunidad. Los resultados tambien apoyan la vision de la especificidad emocional en la reaccion afectiva moral: los participantes en la India y tambien en Gran Bretana mostraron ira en respuesta a la transgresion contra la autonomia y desprecio en respuesta a la violacion de la comunidad. De forma importante, estos resultados amplian los estudios anteriores demostrando la importancia de la especificidad emocional en las reacciones morales frente a la categorizacion o resolucion de los dilemas. Adicionalmente, las medidas de las diferencias individuales en el respeto para personas moderan las reacciones a la transgresion moral. Especificamente, los participantes con alto respeto para personas fueron menos negativos a la hora de violar la etica de la comunidad pero no la etica de la autonomia. Estos resultados subrayan la importancia de estudiar las respuestas emocionales especificas en el dominio moral e introducen una variable de diferencias individuales significativas, respeto para personas, dentro de la psicologia de la moralidad. PMID- 22043851 TI - Workaholism and work-life imbalance: does cultural origin influence the relationship? AB - In recent years, workaholism has become prevalent throughout organizations and has captured the attention of organizational leaders as well as the academic and scientific communities. Most research in this area has focused on the negative consequences of workaholism, specifically work-life imbalance. One area of research that has largely been ignored is the potential influence of demographic variables on the relationship between workaholism and work-life imbalance. Therefore, the current study focused on how cultural origin might influence the intensity of this relationship. Based on relative deprivation theory and previous empirical work, it was expected that cultural origin would moderate the relationship between workaholism and work-life imbalance. Specifically, it was predicted that Caucasian participants would score higher on levels of workaholism than Black participants, and that the relationship between workaholism and work life imbalance would be stronger for Caucasians than for Blacks. The results revealed that high levels of workaholism were significantly correlated with high levels of work-life imbalance. However, results also indicated that cultural origin did not moderate the relationship between workaholism and work-life imbalance, and there was no significant mean difference between Caucasian and Black participants on our measure of workaholism. These findings are important in that it is essential for employers to be aware of workaholic tendencies so they can better handle the negative consequences that result for the organization, and to also help promote the well-being of their employees. En los ultimos anos la adiccion al trabajo se ha vuelto muy popular en las organizaciones y ha capturado la atencion tanto de lideres organizacionales, asi como de las comunidades cientificas y academicas. La mayoria de investigaciones en esta area se han focalizado en las consequencias negativas de la adiccion al trabajo (workoholismo), especificamente en el desequilibrio entre trabajo-vida. Una area de investigacion que ha sido ignorada por mucho tiempo es la influencia potencial de las variables demograficas sobre la relacion entre adiccion al trabajo y el desequilibrio trabajo-vida. Por este motivo es que el presente estudio se focalizo en como el origen cultural puede influenciar la intensidad de esta relacion. Tomando como base la teoria de la deprivacion relativa y estudios empiricos previos, se espero que el origen cultural moderaria la relacion entre adiccion al trabajo y desequilibrio trabajo-vida. Especificamente se pudo predecir que los participantes caucasicos mostraron mas elevados puntajes en los niveles de adiccion al trabajo que los participantes negros, y que la relacion entre adiccion al trabajo y desequilibrio trabajo-vida era mas intensa entre los caucasicos que entre los negros. Los resultados revelaron que elevados niveles de adiccion al trabajo correlacionaron significativamente con altos niveles de desequilibrio trabajo-vida. Sin embargo los resultados tambien revelaron que el origen cultural no moderaba la relacion entre adiccion al trabajo y desequilibrio trabajo-vida, y que ademas no habia una diferencia significativa de medias entre los participantes caucasicos y negros respecto de nuestras mediciones de adiccion al trabajo. Estos resultados son importantes en la medida en que es esencial para los empleadores el ser conscientes respecto de las tendencias de adiccion al trabajo, lo que les permitira manejar con mayor efectividad las consequencias negativas para la empresa resultantes de estas tendencias, y por otro lado apoyar a sus empleados en la promocion de su bienestar. Au cours des dernieres annees, le travaillolisme (workaholism) a pris de l'ampleur dans les organisations et a capte l'attention a la fois des dirigeants d'organisations et des communautes academique et scientifique. La majorite de la recherche dans ce domaine fut orientee sur les consequences negatives du travaillolisme et, plus specifiquement, sur le conflit travail-vie. Un champ de recherche qui a ete largement ignore est l'influence potentielle des variables demographiques sur la relation entre le travaillolisme et le conflit travail-vie. La presente etude visait a comprendre comment l'origine culturelle peut influencer l'intensite de cette relation. Se basant sur la theorie de la privation relative et sur les travaux empiriques anterieurs, il etait attendu que l'origine culturelle allait jouer un role moderateur dans la relation entre le travaillolisme et le conflit travail-vie. Plus specifiquement, il etait predit que les participants caucasiens allaient obtenir des scores plus eleves de travaillolisme comparativement aux participants noirs, et que la relation entre le travaillolisme et le conflit travail-vie allait etre plus forte pour les caucasiens que pour les noirs. Les resultats ont revele que des niveaux eleves de travaillolisme etaient significativement correles avec des niveaux eleves de conflit travail-vie. Cependant, les resultats ont aussi indique que l'origine culturelle ne modere pas la relation entre le travaillolisme et le conflit travail-vie. De plus, il n'y avait pas de difference significative entre les participants caucasiens et les participants noirs sur notre mesure de travaillolisme. Ces resultats sont importants puisqu'il est essentiel pour les employeurs d'etre a l'affut des tendances travaillolistes pour qu'ils puissent mieux en gerer les consequences negatives pour l'organisation, ainsi que pour aider a promouvoir le bien-etre de leurs employes. diferenciaban en algunos aspectos. PMID- 22043852 TI - Effects of excitation energy on the autodetachment lifetimes of small iodide doped ROH clusters (R?H-, CH3-, CH3CH(2)-). AB - The effect of excitation energy on the lifetimes of the charge-transfer-to solvent (CTTS) states of small (4 <= n <= 10) iodide-doped water and alcohol clusters was explored using femtosecond time-resolved photoelectron imaging. Excitation of the CTTS state at wavelengths ranging from 272 to 238 nm leads to the formation of the I...(ROH)(n)(-) (R?H-, CH(3)-, and CH(3)CH(2)-) species, which can be thought of as a vibrationally excited bare solvent cluster anion perturbed by an iodine atom. Autodetachment lifetimes for alcohol-containing clusters range from 1 to 71 ps, while water clusters survive for hundreds of ps in this size range. Autodetachment lifetimes were observed to decrease significantly with increasing excitation energy for a particular number and type of solvent molecules. The application of Klots' model for thermionic emission from clusters to I(-)(H(2)O)(5) and I(-)(CH(3)OH)(7) qualitatively reproduces experimental trends and reveals a high sensitivity to energy parametrization while remaining relatively insensitive to the number of vibrational modes. Experimental and computational results therefore suggest that the rate of electron emission is primarily determined by the energetics of the cluster system rather than by details of molecular structure. PMID- 22043854 TI - Hierarchical Bayesian models to assess between- and within-batch variability of pathogen contamination in food. AB - Assessing within-batch and between-batch variability is of major interest for risk assessors and risk managers in the context of microbiological contamination of food. For example, the ratio between the within-batch variability and the between-batch variability has a large impact on the results of a sampling plan. Here, we designed hierarchical Bayesian models to represent such variability. Compatible priors were built mathematically to obtain sound model comparisons. A numeric criterion is proposed to assess the contamination structure comparing the ability of the models to replicate grouped data at the batch level using a posterior predictive loss approach. Models were applied to two case studies: contamination by Listeria monocytogenes of pork breast used to produce diced bacon and contamination by the same microorganism on cold smoked salmon at the end of the process. In the first case study, a contamination structure clearly exists and is located at the batch level, that is, between batches variability is relatively strong, whereas in the second a structure also exists but is less marked. PMID- 22043853 TI - Using metal complex reduced states to monitor the oxidation of DNA. AB - Metallointercalating photooxidants interact intimately with the base stack of double-stranded DNA and exhibit rich photophysical and electrochemical properties, making them ideal probes for the study of DNA-mediated charge transport (CT). The complexes [Rh(phi)(2)(bpy')](3+) (phi = 9,10 phenanthrenequinone diimine; bpy' = 4-methyl-4'-(butyric acid)-2,2'-bipyridine), [Ir(ppy)(2)(dppz')](+) (ppy = 2-phenylpyridine; dppz' = 6-(dipyrido[3,2-a:2',3' c]phenazin-11-yl)hex-5-ynoic acid), and [Re(CO)(3)(dppz)(py')](+) (dppz = dipyrido[2,3-a:2',3'-c]phenazine; py' = 3-(pyridin-4-yl)-propanoic acid) were each covalently tethered to DNA to compare their photooxidation efficiencies. Biochemical studies show that upon irradiation, the three complexes oxidize guanine by long-range DNA-mediated CT with the efficiency: Rh > Re > Ir. Comparison of spectra obtained by spectroelectrochemistry after bulk reduction of the free metal complexes with those obtained by transient absorption (TA) spectroscopy of the conjugates suggests that the reduced metal states form following excitation of the conjugates at 355 nm. Electrochemical experiments and kinetic analysis of the TA decays indicate that the thermodynamic driving force for CT, variations in the efficiency of back electron transfer, and coupling to DNA are the primary factors responsible for the trend observed in the guanine oxidation yields of the three complexes. PMID- 22043855 TI - High-performance, all-solution-processed organic nanowire transistor arrays with inkjet-printing patterned electrodes. AB - Organic nanowire (NW) transistor arrays with a mobility of as high as 1.26 cm(2).V(-1).S(-1) are fabricated by combining the dip-coating process to align the NW into arrays with the inkjet printing process to pattern the source/drain electrodes. A narrow gap of ~20 MUm has been obtained by modifying the inkjet process. The all-solution process is proven to be a low-cost, high-yield, simple approach to fabricating high-performance organic NW transistor arrays over a large area. PMID- 22043856 TI - Hydrogen exchange mass spectrometry of bacteriorhodopsin reveals light-induced changes in the structural dynamics of a biomolecular machine. AB - Many proteins act as molecular machines that are fuelled by a nonthermal energy source. Examples include transmembrane pumps and stator-rotor complexes. These systems undergo cyclic motions (CMs) that are being driven along a well-defined conformational trajectory. Superimposed on these CMs are thermal fluctuations (TFs) that are coupled to stochastic motions of the solvent. Here we explore whether the TFs of a molecular machine are affected by the occurrence of CMs. Bacteriorhodopsin (BR) is a light-driven proton pump that serves as a model system in this study. The function of BR is based on a photocycle that involves trans/cis isomerization of a retinal chromophore, as well as motions of transmembrane helices. Hydrogen/deuterium exchange (HDX) mass spectrometry was used to monitor the TFs of BR, focusing on the monomeric form of the protein. Comparative HDX studies were conducted under illumination and in the dark. The HDX kinetics of BR are dramatically accelerated in the presence of light. The isotope exchange rates and the number of backbone amides involved in EX2 opening transitions increase roughly 2-fold upon illumination. In contrast, light/dark control experiments on retinal-free protein produced no discernible differences. It can be concluded that the extent of TFs in BR strongly depends on photon driven CMs. The light-induced differences in HDX behavior are ascribed to protein destabilization. Specifically, the thermodynamic stability of the dark-adapted protein is estimated to be 5.5 kJ mol(-1) under the conditions of our work. This value represents the free energy difference between the folded state F and a significantly unfolded conformer U. Illumination reduces the stability of F by 2.2 kJ mol(-1). Mechanical agitation caused by isomerization of the chromophore is transferred to the surrounding protein scaffold, and subsequently, the energy dissipates into the solvent. Light-induced retinal motions therefore act analogously to an internal heat source that promotes the occurrence of TFs. Overall, our data highlight the potential of HDX methods for probing the structural dynamics of molecular machines under "engine on" and "engine off" conditions. PMID- 22043857 TI - Three-dimensional nanostructures as highly efficient generators of second harmonic light. AB - Plasmonic nanostructures enable the generation of large electromagnetic fields confined to small volumes, potentially providing a route for the development of nanoengineered nonlinear optical media. A metal-capped hemispherical nanoparticle, also known as a nanocup, generates second harmonic light with increasing intensity as the angle between the incident fundamental beam and the nanocup symmetry axis is increased. Nanoparticle orientation also modifies the emission direction of the second harmonic light. With conversion efficiencies similar to those of inorganic SHG crystals, these structures provide a promising approach for the design and fabrication of stable, synthetic second-order nonlinear optical materials tailored for specific wavelengths. PMID- 22043858 TI - Artificial microvascular network: a new tool for measuring rheologic properties of stored red blood cells. AB - BACKGROUND: The progressive deterioration of red blood cell (RBC) rheologic properties during refrigerated storage may reduce the clinical efficacy of transfusion of older units. STUDY DESIGN AND METHODS: This article describes the development of a microfluidic device designed to test the rheologic properties of stored RBCs by measuring their ability to perfuse an artificial microvascular network (AMVN) comprised of capillary-size microchannels arranged in a pattern inspired by the real microvasculature. In the AMVN device, the properties of RBCs are evaluated by passing a 40% hematocrit suspension of RBCs through the network and measuring the overall perfusion rate. RESULTS: The sensitivity of the AMVN device to the storage-induced change in rheologic properties of RBCs was tested using five prestorage leukoreduced RBC units stored in AS-1 for 41 days. The AMVN perfusion rate for stored RBCs was 26 +/- 4% (19%-30%) lower than for fresh RBCs. Washing these stored RBCs in saline improved their performance by 41 +/- 6% (the AMVN perfusion rate for washed stored RBCs was still 15 +/- 2% lower than for fresh RBCs). CONCLUSIONS: The measurements performed using the AMVN device confirm a significant decline in the rheologic properties of RBCs in units nearing expiration and demonstrate the sensitivity of the device to these storage induced changes. The AMVN device may be useful for testing the effect of new storage conditions, additive solutions, and rejuvenation strategies on the rheologic properties of stored RBCs in vitro. PMID- 22043859 TI - Quality clinical placements for undergraduate nursing students: a cross-sectional survey of undergraduates and supervising nurses. AB - AIM: This article is a report of a mixed method study of the quality of clinical placements for second year undergraduate nursing students in an acute care hospital. BACKGROUND: In response to the current and predicted workforce shortages, greater numbers of nursing undergraduate places are being offered at tertiary institutions. This means that requests for clinical places in hospitals to support undergraduate students has risen. Little is known about the impact of increased numbers on the quality of clinical placement as a learning experience and this is of concern as demand grows and the means of assessing capacity is still unknown. METHODS: A 5-point Likert Scale questionnaire, including free text fields, was administered to undergraduates (n = 178), clinical facilitators (n = 22) and supervising ward nurses (n = 163) at two time points in 2009. The survey targeted the quality of the clinical placement in four domains: welcoming and belongingness; teaching and learning; feedback; confidence and competence. Findings. The findings demonstrated consistently high scoring of the clinical placement experience by both undergraduates and registered nurses. There were higher ratings of levels of support from clinical facilitators compared to supervising ward nurses evident in data associated with the items on the questionnaire relating to teaching and learning. CONCLUSION: The results are indicative of the professional commitment of nursing staff to support the next generation of nurses. The findings also give a mechanism to communicate outcomes of undergraduate support to nurses in practice, and highlight steps which can be taken to ensure high quality clinical placement continues. PMID- 22043860 TI - Effect of oestradiol and pathogen-associated molecular patterns on class II mediated antigen presentation and immunomodulatory molecule expression in the mouse female reproductive tract. AB - Cells of the female reproductive tract (FRT) can present antigen to naive and memory T cells. However, the effects of oestrogen, known to modulate immune responses, on antigen presentation in the FRT remain undefined. In the present study, DO11.10 T-cell antigen receptor transgenic mice specific for the class II MHC-restricted ovalbumin (OVA) 323-339 peptide were used to study the effects of oestradiol and pathogen-associated molecular patterns on antigen presentation in the FRT. We report here that oestradiol inhibited antigen presentation of OVA by uterine epithelial cells, uterine stromal cells and vaginal cells to OVA-specific memory T cells. When ovariectomized animals were treated with oestradiol for 1 or 3 days, antigen presentation was decreased by 20-80%. In contrast, incubation with PAMP increased antigen presentation by epithelial cells (Pam(3)Cys), stromal cells (peptidoglycan, Pam(3)Cys) and vaginal cells (Pam(3)Cys). In contrast, CpG inhibited both stromal and vaginal cell antigen presentation. Analysis of mRNA expression by reverse transcription PCR indicated that oestradiol inhibited CD40, CD80 and class II in the uterus and CD40, CD86 and class II in the vagina. Expression in isolated uterine and vaginal cells paralleled that seen in whole tissues. In contrast, oestradiol increased polymeric immunoglobulin receptor mRNA expression in the uterus and decreased it in the vagina. These results indicate that antigen-presenting cells in the uterus and vagina are responsive to oestradiol, which inhibits antigen presentation and co-stimulatory molecule expression. Further, these findings suggest that antigen-presenting cells in the uterus and vagina respond to selected Toll-like receptor agonists with altered antigen presentation. PMID- 22043861 TI - Relative efficiency of porcine and human cytotoxic T-lymphocyte antigen 4 immunoglobulin in inhibiting human CD4+ T-cell responses co-stimulated by porcine and human B7 molecules. AB - alpha1,3-Galactosyltransferase gene-knockout pigs transgenic for porcine cytotoxic T-lymphocyte antigen 4 immunoglobulin (pCTLA4-Ig) have been produced to reduce T-cell-mediated rejection following xenotransplantation. The level of soluble pCTLA4-Ig in their blood was greatly in excess of the therapeutic level in patients, rendering the pigs immune-incompetent. Soluble pCTLA4-Ig produced by these transgenic pigs was evaluated for binding to porcine and human (h) B7 molecules, and for its inhibitory effect on allogeneic and xenogeneic human T cell responses. Porcine CTLA4-Ig-expressing peripheral blood mononuclear cells (PBMCs) and aortic endothelial cells (AECs) were evaluated for their direct inhibitory effect on hCD4+ T-cell responses. Soluble pCTLA4-Ig and purified hCTLA4-Ig showed similar binding to pB7 molecules, but pCTLA4-Ig showed significantly less binding to hB7 molecules. The pCTLA4-Ig and hCTLA4-Ig inhibited the response of hCD4+ T cells to pAECs equally, but pCTLA4-Ig was less successful in inhibiting the human allogeneic response. The hCD4+ T-cell response to PBMCs from pCTLA4-Ig pigs was significantly lower than that of non-pCTLA4-Ig pigs. Although pCTLA4-Ig was detected in the cytoplasm of pCTLA4-Ig-expressing pAECs, only a minimal level of soluble pCTLA4-Ig was detected in the supernatant during culture, and pCTLA4-Ig-expressing pAECs did not inhibit the xenogeneic direct human T-cell response. High-level tissue-specific production of pCTLA4-Ig may be required for sufficient immunosuppression for organ or cell (e.g., islets) transplantation. PMID- 22043862 TI - Spatial competition with Lactococcus lactis in mixed-species continuous-flow biofilms inhibits Listeria monocytogenes growth. AB - Surfaces in industrial settings provide a home for resident biofilms that are likely to interact with the attachment, growth and survival of pathogens such as Listeria monocytogenes. Experimental results have indicated that L. monocytogenes cells were inhibited by the presence of a model resident flora (Lactococcus lactis) in dual-species continuous flow-biofilms, and are spatially restricted to the lower biofilm layers. Using a new, simplified individual-based model (IBM) that simulates bacterial cell growth in a three-dimensional space, the spatial arrangements of the two species were reconstructed and their cell counts successfully predicted. This model showed that the difference in generation times between L. monocytogenes and L. lactis cells during the initial stages of dual species biofilm formation was probably responsible for the species spatialization observed and the subsequent inhibition of growth of the pathogen. PMID- 22043863 TI - Increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area during cocaine abstinence is associated with increased histone acetylation at BDNF exon I-containing promoters. AB - Recent evidence suggests that the persistence of cocaine seeking during periods of protracted drug abstinence following chronic cocaine exposure is mediated, in part, by neuroadaptations in the mesolimbic dopamine system. Specifically, incubation of cocaine-seeking behavior coincides with increased brain-derived neurotrophic factor (BDNF) protein expression in the ventral tegmental area (VTA). However, the molecular mechanisms that regulate time-dependent changes in VTA BDNF protein expression during cocaine abstinence are unclear. The goal of these experiments was to determine whether VTA BDNF transcript levels are altered following cocaine abstinence and identify the molecular mechanisms regulating cocaine-induced changes in VTA BDNF transcription. Rats were allowed to self administer cocaine (0.25 mg/infusion, i.v.) for 14 days on a fixed-ratio schedule of reinforcement followed by 7 days of forced drug abstinence. BDNF protein and exon I-containing transcripts were significantly increased in the VTA of cocaine experienced rats following 7 days of forced drug abstinence compared to yoked saline controls. Cocaine-induced changes in BDNF mRNA were associated with increased acetylation of histone 3 and binding of CREB-binding protein to exon I containing promoters in the VTA. Taken together, these results suggest that drug abstinence following cocaine self-administration remodels chromatin in the VTA resulting in increased expression of BDNF, which may contribute to neuroadaptations underlying cocaine craving and relapse. PMID- 22043865 TI - Low-grade gliomas in adults. AB - In recent years, advances in the understanding of low-grade glioma (LGG) biology have driven new paradigms in molecular markers, diagnostic imaging, operative techniques and technologies, and adjuvant therapies. Taken together, these developments are collectively pushing the envelope toward improved quality of life and survival. In this article, the authors evaluate the recent literature to synthesize a comprehensive review of LGGs in the modern neurosurgical era. PMID- 22043864 TI - Rep-Seq: uncovering the immunological repertoire through next-generation sequencing. AB - Recent scientific discoveries fuelled by the application of next-generation DNA and RNA sequencing technologies highlight the striking impact of these platforms in characterizing multiple aspects in genomics research. This technology has been used in the study of the B-cell and T-cell receptor repertoire. The novelty of immunosequencing comes from the recent rapid development of techniques and the exponential reduction in cost of sequencing. Here, we describe some of the technologies, which we collectively refer to as Rep-Seq (repertoire sequencing), to portray achievements in the field and to present the essential and inseparable role of next-generation sequencing to the understanding of entities in immune response. The large Rep-Seq data sets that should be available in the near future call for new computational algorithms to segue the transition from 'classic' molecular-based analysis to system-wide analysis. The combination of new algorithms with high-throughput data will form the basis for possible new clinical implications in personalized medicine and deeper understanding of immune behaviour and immune response. PMID- 22043866 TI - Improving the quality of life for multiple sclerosis patients using the nurse based home visiting model. AB - PURPOSE: Multiple sclerosis (MS) sufferers have a high prevalence of co-morbidity associated with poor quality of life, high health care costs and increased risk for adverse outcomes. These patients are often lacking in optimal home care, which may result in subsequent hospital readmissions. However, a specific nurse based home visiting model for patients with MS is not yet available in Turkey. The aim of this study was to determine the effects of nursing interventions according to The North American Nursing Diagnosis Association (NANDA). Using the NANDA guidelines, the aim of this study was to determine the effect of home visit nursing interventions on the many challenges and quality-of-life (QOL) issues faced by patients with MS. METHODS: This study used a pretest-posttest experimental group design. The study sample of 45 patients with MS, who had previously registered with the MS Society, had 21 participants in the intervention group and 24 in the control group. Data were collected with the 'General Questionnaire Form' and 'Symptom Evaluation Form' and 'Multiple Sclerosis Quality-of-Life Scale' (MSQOL-54). The NANDA classification system of care plans for conducting eight home visits with the intervention group was also used. Our intervention would identify symptoms, give training, consulting and care services and be able to recognize when referrals to other medical professionals might be necessary. The control group would receive the usual care with just two visits. RESULTS: There was a statistically significant difference between the intervention and control groups regarding the MSQOL-54P score change (p = 0.02), but a nonsignificant difference for the MSQOL-54M. CONCLUSION: This model helped to achieve an improvement trend in the QOL scores of the MS patient intervention group. This home visit model can also be used to increase the quality of care and quality of life for patients with MS. PMID- 22043867 TI - Milk consumption and bladder cancer risk: a meta-analysis of published epidemiological studies. AB - Studies investigating the association of milk consumption with bladder cancer risk have reported inconsistent findings. We conducted a meta-analysis of published cohort and case-control studies to pool the risk estimates of the association between milk intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of odds ratio (OR) associated with the highest vs. the lowest category of milk intake using fixed- or random-effect models depending on the heterogeneity of effects among studies. Nineteen cohort and case-control studies were eligible for inclusion. High milk intake was significantly associated with decreased risk of bladder cancer (OR, 0.84; 95% CI, 0.71-0.97) when comparing the highest with the lowest category of milk intake. The inverse association was stronger in Asia (OR, 0.60; 95% CI, 0.40-0.81) than North America (OR, 0.89; 95% CI, 0.76-1.03), and no association was observed in Europe (OR, 1.05; 95% CI, 0.85-1.26). This relationship also varied significantly by specific dairy products. Our results suggest that milk may be related to the reduction of bladder cancer risk. Further studies need to clarify the biological mechanisms. PMID- 22043869 TI - Charge trapping and storage by composite P3HT/PC60BM nanoparticles investigated by fluorescence-voltage/single particle spectroscopy. AB - Fluorescence-voltage/single particle spectroscopy (F-V/SPS) was employed to study exciton-hole polaron interactions and interfacial charge transfer processes for pure poly(3-hexylthiophene) (P3HT) nanoparticles (NPs) and composite P3HT/PC(60)BM NPs in functioning hole-injection devices. F-V/SPS data collected on a particle-by-particle basis reveal an apparent bistability in the fluorescence-voltage modulation curves for composite NPs of P3HT and [6,6]-phenyl C(61)-butyric acid methyl ester (PC(60)BM) that is absent for pure P3HT NPs. A pronounced deep trapping of free electrons photogenerated from the composite P3HT/PC(60)BM NPs at the NP/dielectric interface and hole trapping by fullerene anions in composite P3HT/PC(60)BM NPs under photoexcitation lies at the basis of this finding. The deep electron trapping effect reported here for composite conjugated polymer/fullerene NPs presents an opportunity for future application of these NPs in nanoscale memory and imaging devices. PMID- 22043868 TI - Enhancing effects of acute psychosocial stress on priming of non-declarative memory in healthy young adults. AB - Social stress affects cognitive processes in general, and memory performance in particular. However, the direction of these effects has not been clearly established, as it depends on several factors. Our aim was to determine the impact of the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) reactivity to psychosocial stress on short-term non-declarative memory and declarative memory performance. Fifty-two young participants (18 men, 34 women) were subjected to the Trier Social Stress Task (TSST) and a control condition in a crossover design. Implicit memory was assessed by a priming test, and explicit memory was assessed by the Rey Auditory Verbal Learning Test (RAVLT). The TSST provoked greater salivary cortisol and salivary alpha-amylase (sAA) responses than the control task. Men had a higher cortisol response to stress than women, but no sex differences were found for sAA release. Stress was associated with an enhancement of priming but did not affect declarative memory. Additionally, the enhancement on the priming test was higher in those whose sAA levels increased more in response to stress (r(48) = 0.339, p = 0.018). Our results confirm an effect of acute stress on priming, and that this effect is related to SNS activity. In addition, they suggest a different relationship between stress biomarkers and the different memory systems. PMID- 22043870 TI - Determination of pesticides and their metabolites in processed cereal samples. AB - Fifteen pesticides including some of their metabolites (disulfoton sulfoxide, ethoprophos, cadusafos, dimethoate, terbufos, disulfoton, chlorpyrifos-methyl, malaoxon, fenitrothion, pirimiphos-methyl, malathion, chlorpyrifos, terbufos sulfone, disulfoton sulfone and fensulfothion) were analysed in milled toasted wheat and maize as well as in wheat flour and baby cereals. The QuEChERS (quick, easy, cheap, effective, rugged and safe) methodology was used and its dispersive solid-phase extraction procedure was optimised by means of an experimental design with the aim of reducing the amount of co-extracted lipids and obtaining a clean extract. Gas chromatography with nitrogen phosphorus detection were used as the separation and detection techniques, respectively. The method was validated in terms of selectivity, recoveries, calibration, precision and accuracy as well as matrix effects. Limits of detection were between 0.07 and 34.8 ug kg(-1) with recoveries in the range of 71-110% (relative standard deviations were below 9%). A total of 40 samples of different origin were analysed. Residues of pirimiphos methyl were found in six of the samples at concentrations in the range 0.08-0.47 mg kg(-1), which were below the MRLs established for this pesticide in cereal grains. Tandem mass spectrometry confirmation was also carried out in order to identify unequivocally the presence of this pesticide. PMID- 22043871 TI - Memory control beliefs and everyday forgetfulness in adulthood: the effects of selection, optimization, and compensation strategies. AB - Controlling for age, gender, education, and self-rated health, the present study used regression analyses to examine the relationships between memory control beliefs and self-reported forgetfulness in the context of the meta-theory of Selective Optimization with Compensation (SOC). Findings from this online survey (N = 409) indicate that, among adult New Zealanders, a higher sense of memory control accounts for a 22.7% reduction in self-reported forgetfulness. Similarly, optimization was found to account for a 5% reduction in forgetfulness while the strategies of selection and compensation were not related to self-reports of forgetfulness. Optimization partially mediated the beneficial effects that some memory beliefs (e.g., believing that memory decline is inevitable and believing in the potential for memory improvement) have on forgetfulness. It was concluded that memory control beliefs are important predictors of self-reported forgetfulness while the support for the SOC model in the context of memory controllability and everyday forgetfulness is limited. PMID- 22043872 TI - Light-induced conical intersections: topological phase, wave packet dynamics, and molecular alignment. AB - In previous publications (J. Phys. B: At., Mol. Opt. Phys.2008, 41, 221001; J. Phys. B: At., Mol. Opt. Phys. 2011, 44, 045603) a novel and physically interesting phenomenon was found in the field of light-matter interactions. It was shown theoretically that exposing a molecule to a laser field can give rise to the appearance of so-called light-induced conical intersections (LICIs). The existence of such LICIs may change significantly the field free physical properties of a molecular system. In this article we review the LICIs in diatomics and provide a new insight to the LICI phenomenon. The sodium dimer is chosen as an explicit sample system. We calculated the Berry phase for a contour that surrounds the point of LICI and found it to be pi, which is the same value as for the case of a "natural" CI in triatomic or larger molecules. We also present results to stress the impact of LICIs on molecular wave packet dynamics and molecular alignment in different electronic states. PMID- 22043873 TI - Spray: single-donor plasma product for room temperature storage. AB - BACKGROUND: Spray-drying techniques are commonly utilized in the pharmaceutical, dairy, and animal feed industries for processing liquids into powders but have not been applied to human blood products. Spray-dried protein products are known to maintain stability during storage at room temperature. STUDY DESIGN AND METHODS: Plasma units collected at the donor facility were shipped overnight at room temperature to a processing facility where single-use spray drying occurred. After 48 hours' storage at room temperature, the spray-dried plasma product was split in two and rehydrated with 1.5% glycine or deionized water and assayed for chemistry analytes and coagulation factors. Matched fresh-frozen plasma was analyzed in parallel as controls. RESULTS: Reconstitution was achieved for both rehydration groups within 5 minutes (n = 6). There was no significant intergroup difference in recovery for total protein, albumin, immunoglobulin (Ig)G, IgA, and IgM (96% or higher). With the exception of Factor VIII (58%), the recovery of clotting factors in the glycine reconstituted products ranged from 72% to 93%. Glycine reconstitution was superior to deionized water. CONCLUSION: We documented proteins and coagulation activities were recovered in physiologic quantities in reconstituted spray-dried plasma products. Further optimization of the spray drying method and reconstitution fluid may result in even better recoveries. Spray drying is a promising technique for preparing human plasma that can be easily stored at room temperature, shipped, and reconstituted. Rapid reconstitution of the microparticles results in a novel plasma product from single donors. PMID- 22043875 TI - Comparison of PM emissions from a commercial jet engine burning conventional, biomass, and Fischer-Tropsch fuels. AB - Rising fuel costs, an increasing desire to enhance security of energy supply, and potential environmental benefits have driven research into alternative renewable fuels for commercial aviation applications. This paper reports the results of the first measurements of particulate matter (PM) emissions from a CFM56-7B commercial jet engine burning conventional and alternative biomass- and, Fischer Tropsch (F-T)-based fuels. PM emissions reductions are observed with all fuels and blends when compared to the emissions from a reference conventional fuel, Jet A1, and are attributed to fuel properties associated with the fuels and blends studied. Although the alternative fuel candidates studied in this campaign offer the potential for large PM emissions reductions, with the exception of the 50% blend of F-T fuel, they do not meet current standards for aviation fuel and thus cannot be considered as certified replacement fuels. Over the ICAO Landing Takeoff Cycle, which is intended to simulate aircraft engine operations that affect local air quality, the overall PM number-based emissions for the 50% blend of F-T fuel were reduced by 34 +/- 7%, and the mass-based emissions were reduced by 39 +/- 7%. PMID- 22043876 TI - Special issue: Iron deficiency and iron deficiency anemia in early infancy; etiology, consequences, prevalence, and prevention. Foreword. PMID- 22043877 TI - Role of the placenta in regulation of fetal iron status. AB - During pregnancy, the developing fetus is entirely dependent on its mother for nutrition and waste disposal, which take place almost exclusively across the placenta. The placenta is, however, not just a passive mediator; it can also regulate the rates and amounts of nutrient transported. This is particularly true for iron transport. This review examines how the fetus, and not the mother, regulates iron uptake and transfer across the placenta, how these processes interact, and how the fetus can modulate iron metabolism in the mother. PMID- 22043878 TI - Maternal iron status: relation to fetal growth, length of gestation, and iron endowment of the neonate. AB - Anemia prevalence is highest in preschool children, women of reproductive age, and women who are pregnant. While the etiology of anemia is multifactorial, iron deficiency is the most commonly recognized nutritional cause. Observational studies imply that supplementation with iron or iron-folic acid should be started early in pregnancy, if not before, in order to prevent low-birth-weight and preterm delivery. Despite this, findings from clinical trials, even those conducted during early pregnancy, are equivocal. Recent follow-up studies of children born to women supplemented with iron-folic acid suggest that mortality is decreased and that the infant's iron endowment reflects the mother's iron status during pregnancy. PMID- 22043879 TI - Iron endowment at birth: maternal iron status and other influences. AB - The iron endowment at birth depends, in large part, on the newborn's birth weight and gestational age. These are determined by many factors, some of which are maternal characteristics, including the following: maternal iron stores at her own birth and during her own early life, maternal growth and development, maternal age at conception, intergenesic intervals, maternal body characteristics and iron status at conception and during early pregnancy, gestational body weight gain, and iron status throughout gestation, particularly at conception and early pregnancy, and gestational body weight gain. Although less studied, paternal influences on the initiation and progression of pregnancy and on maternal environmental exposures are also important. Even though tools for the quantitative evaluation of women's iron status are very well developed, the quantitative estimation of body iron in the newborn and young infant remains a challenge. This article describes the crucial role played by the placenta in protecting the embryo and the fetus. In addition, neonatal health, particularly early in pregnancy, is briefly addressed, as are some important aspects of antenatal nutritional interventions that include iron. PMID- 22043880 TI - Timing of umbilical cord clamping: effect on iron endowment of the newborn and later iron status. AB - The optimal timing of umbilical cord clamping has been debated in the scientific literature for at least the last century, when cord clamping practices shifted from delayed towards immediate clamping. Recent research provides evidence for the beneficial effect of delayed cord clamping on infant iron status. The present review describes the physiological basis for the impact of cord clamping time on total body iron at birth and the relationship between birth body iron, as affected by cord clamping time, and iron status later in infancy. This research is discussed in the context of current clamping practices, which tend towards early cord clamping in most settings, as well as the high levels of anemia present in young infants in many countries worldwide. PMID- 22043881 TI - Consumption of cow's milk as a cause of iron deficiency in infants and toddlers. AB - Consumption of cow's milk (CM) by infants and toddlers has adverse effects on their iron stores, a finding that has been well documented in many localities. Several mechanisms have been identified that may contribute to iron deficiency in this young population group. The most important of these is probably the low iron content of CM, which makes it difficult for infants to obtain the amounts of iron needed for growth. A second mechanism is the occult intestinal blood loss associated with CM consumption during infancy, a condition that affects about 40% of otherwise healthy infants. Loss of iron in the form of blood diminishes with age and ceases after the age of 1 year. A third mechanism is the inhibition of non-heme iron absorption by calcium and casein, both of which are present in high amounts in CM. Fortification of CM with iron, as practiced in some countries, can protect infants and toddlers against CM's negative effects on iron status. Consumption of CM produces a high renal solute load, which leads to a higher urine solute concentration than consumption of breast milk or formula, thereby narrowing the margin of safety during dehydrating events, such as diarrhea. The high protein intake from CM may also place infants at increased risk of obesity in later childhood. It is thus recommended that unmodified, unfortified CM not be fed to infants and that it be fed to toddlers in modest amounts only. PMID- 22043882 TI - Long-term brain and behavioral consequences of early iron deficiency. AB - Early iron deficiency not only affects brain and behavioral function during the period of iron deficiency, it persists long after treatment. The mechanisms include long-term alterations in dopamine metabolism, myelination, and hippocampal structure and function. Recent studies have demonstrated long-term genomic changes, which suggests the regulation of brain function is fundamentally altered. PMID- 22043883 TI - Estimating the prevalence of iron deficiency in the first two years of life: technical and measurement issues. AB - National-level data on iron deficiency is not available for most countries and many rely on the prevalence of anemia as a proxy estimate, assuming that approximately 50% of anemia cases are caused by iron deficiency. Anemia, however, has multiple causal factors and the risk attributable to any one cause will depend on its relative importance in a population in relation to other causes. The present review summarizes current estimates on the prevalence of iron deficiency and anemia in children younger than 2 years and evaluates the strengths and weaknesses of currently available indicators of iron deficiency in children. Anemia prevalence is insufficient to estimate the prevalence of iron deficiency in children younger than 2 years. The methods widely used to assess iron deficiency at the population level rely on venous blood samples and are complicated and costly to implement. PMID- 22043884 TI - Evaluation of meat as a first complementary food for breastfed infants: impact on iron intake. AB - The rationale for promoting the availability of local, affordable, non-fortified food sources of bioavailable iron in developing countries is considered in this review. Intake of iron from the regular consumption of meat from the age of 6 months is evaluated with respect to physiological requirements. Two major randomized controlled trials evaluating meat as a first and regular complementary food are described in this article. These trials are presently in progress in poor communities in Guatemala, Pakistan, Zambia, Democratic Republic of the Congo, and China. PMID- 22043885 TI - Iron deficiency and iron-deficiency anemia in the first two years of life: strategies to prevent loss of developmental potential. AB - This article examines the association of iron deficiency (ID) and iron deficiency anemia (IDA) with children's development and behavior, with the goal of providing recommendations to prevent the developmental loss associated with these conditions. Children's risk for ID and IDA is particularly high during the second 6 months of life when prenatal stores are depleted. Longitudinal studies from infancy through adolescence and early adulthood suggest that socioemotional development is uniquely vulnerable to ID and IDA, perhaps being associated with shared neural pathways, and the effects of early iron deficiencies may be irreversible. In addition to direct effects on brain function, ID and IDA may also affect child development indirectly through non-responsive mother-child interactions. Maternal ID is a global problem that may contribute to high rates of maternal depression and non-responsive caregiving. Intervention trials illustrate that children benefit from both nutritional intervention and early learning interventions that promote responsive mother-child interactions. Recommendations to reduce the developmental loss associated with ID and IDA are to reduce the incidence of these conditions by efforts to prevent premature birth, delay cord clamping, ensure adequate maternal iron status, provide iron rich complementary foods, and ensure access to postnatal interventions that promote responsive mother-infant interaction patterns and early learning opportunities for infants. PMID- 22043886 TI - Iron supplementation of breastfed infants. AB - Reported here are three studies performed with the objective of finding ways to improve the iron status of breastfed infants and to prevent iron deficiency (ID). Participating infants were exclusively breastfed until 4 months of age; thereafter, they could receive complementary foods and, in some studies, supplemental formula. In the first study, infants were given medicinal iron between the ages of 1 and 5.5 months. During this period, iron status improved and ID was prevented; however, these benefits did not continue after the intervention ceased. In the second study, infants received medicinal iron or an equivalent amount of iron from an iron-fortified cereal between the ages of 4 and 9 months. Again, iron supplementation largely prevented ID from occurring, while non-anemic ID and ID anemia occurred in the control group as well as in the intervention groups before the intervention began. In the third study, infants received dry cereals fortified with electrolytic iron or with ferrous fumarate between the ages of 4 and 9 months. The cereals were equally effective in providing relative protection from ID. The results of these three studies indicate it is possible to protect breastfed infants from ID and IDA. PMID- 22043887 TI - Strategies to prevent iron deficiency and improve reproductive health. AB - Anemia and iron deficiency affect billions of people worldwide, especially women of reproductive age, pregnant women, and young children. Many countries have iron and folic acid supplementation programs for pregnant women. However, the impact of these programs is uncertain. Multiple-micronutrient supplementation during pregnancy has been advocated; however, it is unclear whether this has additional advantages. Overall, programs have shown only modest impact on increasing birth weight. This review discusses the present state of knowledge on interventions to improve iron status during pregnancy and reproductive health, and investigates other possibilities such as supplementation prior to conception to improve maternal and child health. PMID- 22043888 TI - Dynamic categorization and slot-filler representation in 4- and 6-year-old children. AB - This experiment was aimed at studying both the role of narrow/contextualized categories in the acquisition/organization of conceptual knowledge and the dynamics of categorization decisions. A forced-choice categorization task contrasting thematic and taxonomic responding was used in 4- and 6-year-old children. Before response alternatives were presented, a conceptual organization was pre-activated by means of a matching between the target stimulus and a thematically related, taxonomically related or slot-filler related object. Although taxonomic sorting was prominent overall, it varied as a function of age and of the nature of the pre-activated relation. Responses in accordance with the thematic or taxonomic activations occurred similarly in 4- and 6-year-old children. Age-related effects were however at work in the case of a slot-filler activation: 4-year-old children considered the contextual/contiguity relations between the stimuli but did not weight the equivalence relations (i.e., same occurrence of responses based on the kind of object in the slot-filler and in the thematic activation conditions). More diversified processes appeared to be at work in 6-year-old children. Slot-filler categories were this time considered throughout both their contextual/contiguity structure and their equivalence relations. Results were discussed in terms of availability of conceptual organizations, flexibility abilities, dynamic categorization and preferences. The focus was on implication of slot-filler representations in the construction of conceptual knowledge and in the development of categorization. An important point was to determine whether the age-related changes observed in the slot-filler activation condition could be consistent with Nelson's ( 1983 ) idea that slot fillers would help passing from a schema-based to a conventional superordinate organization. PMID- 22043889 TI - Effects of positive and negative delusional ideation on memory. AB - We investigated the relationship between levels of delusional ideation (whether positive or negative delusions) and the activation and distortion of memory by using pairs of positive and negative adjectives describing personality traits where those adjectives had similar meanings. We presented one of each pair of adjectives in the learning phase. Immediately after the learning phase in Experiment 1, we asked whether each adjective had been presented. Participants with high (positive or negative) delusional ideation were more likely to indicate that they had learned adjectives that they had not actually learned. This finding suggested that non-learned positive (or negative) adjectives that were associated with learned negative (or positive) adjectives were more likely to be activated in participants prone to positive (or negative) delusional ideation. However, in Experiment 2, two forced-choice tests were conducted immediately after the learning phase. In this context, participants, regardless of their proneness to delusional ideation, could almost always correctly distinguish what had and had not been presented, suggesting that the activation of learned items was still stronger than that for non-learned items in the immediate test. As time passed, the proportion of false alarms for positive or negative adjectives was higher in the two forced-choice tests among those with high proneness to (positive or negative) delusional ideation, suggesting that participants with delusional ideation were increasingly likely to depend on internal conditions for retrieval over time. Nous avons examine la relation entre les niveaux d'ideation illusoire (qu'elle soit positive ou negative) et l'activation et la distorsion de la memoire, en utilisant des paires d'adjectifs positifs et negatifs a significations similaires decrivant des traits de personnalite. Nous avons presente un membre de chaque paire d'adjectifs lors d'une phase d'apprentissage. Dans une premiere experience, immediatement apres la phase d'apprentissage, nous avons demande si chaque adjectif avait ete presente. Les participants ayant un niveau d'ideation illusoire (positive ou negative) eleve etaient plus susceptibles d'indiquer qu'ils avaient appris les adjectifs qu'ils n'avaient pas appris. Ce resultat suggerait que les adjectifs positifs (ou negatifs) non appris qui etaient associes a des adjectifs negatifs (ou positifs) appris etaient plus susceptibles d'etre actives chez les participants portes a l'ideation illusoire positive (ou negative). Dans une deuxieme experience, deux tests a choix forces ont ete menes immediatement apres la phase d'apprentissage. Dans ce contexte, les participants, independamment de leur tendance a l'ideation illusoire, pouvaient presque toujours distinguer correctement ce qui avait ete presente de ce qui n'avait pas ete presente, suggerant que l'activation des items appris etait encore plus forte que celle des items non appris dans le test immediat. Avec le temps, la proportion de fausses alarmes pour les adjectifs positifs ou negatifs etait plus elevee dans les deux tests a choix forces chez les participants portes a l'ideation illusoire (positive ou negative), ce qui suggere que les participants avec ideation illusoire etaient de plus en plus susceptibles de dependre de leurs conditions internes lors du rappel a mesure que le temps passait. En este estudio se investigo la relacion entre los niveles de ideacion delusional (tanto delusiones positivas como negativas) y la activacion y distorsion de la memoria a traves del uso de pares de adjetivos positivos y negativos que describen rasgos de personalidad. Estos pares de adjetivos tenian significados similares. En la fase de aprendizaje se presento un miembro de cada par de adjetivos. Inmediatamente despues de la fase de aprendizaje se realizo el primer experimento, en el cual se pregunto al participanten si es que se le habian presentado cada uno de los adjetivos. Los participantes con elevada ideacion delusiva (positiva o negativa) reportaran con una mayor probabilidad haber aprendido adjetivos que en realidad no se les habia presentado. Este hallazgo sugiere que adjetivos positivos (o negativos) no aprendidos que estaban asociados con adjetivos negativos (o positivos) aprendidos, tenian una mayor probabilidad de ser activados en participantes propensos a una ideacion delusiva positiva (o negativa). En el segundo experimento se llevaron a cabo inmediatamente despues de la fase de aprendizaje dos pruebas de decision forzada. En este contexto se pudo observar que los participantes a pesar de su tendencia hacia una ideacion delusional, lograron distinguir en la mayoria de los casos correctamente entre los adjetivos que les fueron presentado y lo que no. Esto sugiere que la activacion de los items aprendidos fue mucho mas intensa que la de los items no aprendidos en el test. Sin embargo se pudo observar en los participantes de las dos pruebas de decision forzada que con el paso del tiempo el porcentaje de falso reconocimiento de adjetivos positivos y negativos fue mas elevado entre aquellas personas con una alta tendencia hacia una ideacion delusional (positiva o negativa). Esto sugiere que en participantes con ideacion delusional el reconocimiento de informacion a lo largo del tiempo probablemente es muy dependiente de condiciones internas. PMID- 22043890 TI - Comparison of brain mechanisms underlying the processing of Chinese characters and pseudo-characters: an event-related potential study. AB - Most Chinese characters are composed of a semantic radical on the left and a phonetic radical on the right. The semantic radical provides the semantic information; the phonetic radical provides information concerning the pronunciation of the whole character. The pseudo-characters in the study consisted of different sub-lexical parts of real Chinese characters and consequently they also had the semantic radical and the phonetic radical. But they were not readable and had no actual meaning. In order to investigate the spatiotemporal cortical activation patterns underlying the orthographic, phonological and semantic processing of Chinese characters, we used event-related brain potentials (ERPs) to explore the processing of Chinese characters and pseudo-characters when 14 healthy Chinese college students viewed the characters passively. Results showed that both Chinese characters and pseudo-characters elicited an evident negative potential peaking around 120 ms (N120), which appeared to reflect initial orthographic distinction and evaluation. Then, Chinese pseudo-characters elicited a more positive ERP deflection (P220) than did Chinese characters 200-250 ms after onset of the stimuli. It was similar to the recognition potential (RP) and might reflect the integration processes of phonological and semantic processing on the basis of early orthographic information. Dipole source analysis of the difference wave (pseudo-characters minus characters) indicated that a generator localized in the left temporal occipital junction contributed to this effect, which was possibly related to phonological and perceptual-semantic information integration. Between 350-450 ms, a greater negativity (N360) in pseudo-characters as compared to characters was found over midline fronto-central scalp regions. Dipole analysis localized the generator of N360 in the right parahippocampal cortex. Therefore, the N360 might be an N400 component and reflect the higher-level semantic activation on the basis of orthographic, phonological and perceptual-semantic processing. La plupart des caracteres chinois sont composes d'un radical semantique a gauche et d'un radical phonetique a droite. Le radical semantique peut fournir de l'information semantique et le radical phonetique peut fournir de l'information concernant la prononciation du caractere entier. Les pseudo-caracteres consistaient en differentes parties sous-lexicales des caracteres chinois reels et, consequemment, ils avaient aussi un radical semantique et un radical phonetique. Mais ils ne pouvaient pas etre lisibles et ils n'ont actuellement aucun sens. Afin d'etudier les patrons d'activation spatiotemporels corticaux sous-jacents aux traitements orthographique, phonologique et semantique des caracteres chinois, nous avons utilise des Potentiels cerebraux relies aux evenements (PRE) pour explorer le traitement des caracteres et des pseudo caracteres chinois aupres de 14 collegiens chinois visionnant les caracteres passivement. Les resultats ont montre qu'a la fois les caracteres et les pseudo caracteres chinois provoquaient un potentiel negatif evident atteignant un sommet autour de 120 ms (N120), ce qui apparaissait refleter la distinction et l'evaluation orthographiques initiales. Puis, les pseudo-caracteres ont provoque une deviation PRE plus positive (P220) que les caracteres chinois entre 200 et 250 ms apres l'apparition des stimuli. Ceci etait similaire au PR (Potentiel de reconnaissance) et pouvait refleter les processus d'integration des traitements phonologique et semantique sur la base de l'information orthographique initiale. L'analyse dipole de source de la difference de courbe (pseudo-caracteres moins caracteres) a indique qu'un generateur localise dans la jonction temporo occipitale gauche contribuait a cet effet, ce qui etait possiblement relie a l'integration de l'information phonologique et perceptuelle-semantique. Entre 350 et 450 ms, une plus grande negativite (N360) fut observee pour les pseudo caracteres comparativement aux caracteres des regions du scalp au-dessus des regions medianes fronto-centrales. L'analyse dipole a localise le generateur de N360 dans le cortex para-hippocampique droit. Ainsi, le N360 pourrait etre une composante N400 et refleter une activation semantique de haut niveau sur la base des traitements orthographique, phonologique et perceptuel-semantique. La mayoria de los caracteres chinos estan compuestos por un radical semantico a la izquierda y un radical fonetico a la derecha. El radical semantico puede proporcionar informacion semantica y el radical fonetico puede proporcionar informacion relacionada con la pronunciacion del caracter entero. Los pseudo caracteres consistieron en diferentes partes sub-lexicas de los caracteres reales chinos y como consecuencia, tambien tenian radicales semanticos y foneticos. Pero estos no se podian leer y tampoco tenian un significado real. Para investigar los patrones de la activacion cortical espaciotemporal subyacentes de los procesamientos ortografico, fonologico y semantico de los caracteres chinos, utilizamos potencial relacionado con eventos (ERPs) para explorar el procesamiento de caracteres chinos y pseudo-caracteres mientras que 14 sanos estudiantes chinos veian los caracteres de forma pasiva. Los resultados demostraron que ambos, caracteres y pseudo-caracteres chinos evocaban potenciales negativos con picos alrededor de los 120 ms (N120), lo cual parece reflejar distincion inicial ortografica y evaluacion. Ademas, los pseudo-caracteres chinos provocaban una desviacion ERP mas positiva (P220) en comparacion con los caracteres chinos entre 200-250 ms despues de la aparicion de los estimulos. Esto fue parecido a RP (potenciales de reconocimiento) y puede reflejar un proceso de integracion del procesamiento fonologico y semantico basado en la informacion ortografica temprana. Un analisis dipolo de la fuente de la onda de diferencia (pseudo-caracteres menos caracteres) indico que un generador localizado en el cruce temporal-occipital izquierdo contribuyo a este efecto, lo cual probablemente tuvo relacion con la integracion de la informacion fonologica y perceptivo-semantica. Se encontro mayor negatividad (N360) entre 350-450 ms, en pseudo-caracteres en comparacion con los caracteres situada sobre las regiones de la linea media fronto-central craneal. Un analisis dipolo localizo un generador de N360 en el cortex parahipocampal derecho. Por tanto, el N360 podria ser un componente de N400 reflejando una activacion semantica de mas alto nivel basado en el procesamiento ortografico, fonologico y perceptivo-semantico. PMID- 22043891 TI - Thinking and feeling in the People's Republic of China: testing the generality of the "laws of emotion". AB - Cognitive theories of emotion assert that emotional reactions to events depend on the manner in which events are interpreted and appraised. From this perspective, the same outcome can produce different emotions. For example, a score of 85% on a test can evoke positive feelings if it is considered a success or negative feelings if it is considered a failure. Among the various appraisal dimensions that have been identified, causal attributions are thought to play a particularly influential role in shaping emotional reactions to various events. For example, success can evoke pride if it is attributed to high ability, gratitude if it is attributed to help from others, relief if it is attributed to a stroke of good fortune, or guilt if it is attained fraudulently or at the expense of others. These cognitive-affective linkages are thought to be universal. In this paper, we report two studies that tested the cross-cultural generality of some of these assumptions. In Study 1, participants from the People's Republic of China were led to succeed or fail on an (alleged) test of their intelligence and creativity. Consistent with previous findings with Western samples, attributions to ability predicted participants' emotional reactions to their test performance, with high ability attributions linked to greater pride following success. In Study 2, we extended these findings with American and Chinese participants, using a different experimental manipulation of success and failure, and a measure of attributions to effort. For both cultural groups, attributions to ability (but not attributions to effort) predicted greater emotional reactions to success. We conclude that attribution-emotion linkages have cross-cultural validity, and that pride is maximized when success is attributed to high ability. PMID- 22043892 TI - Longitudinal effects of egoistic and fraternal relative deprivation on well-being and protest. AB - According to the social justice literature, fraternal relative deprivation causes protest, but has little impact on well-being. We consider this view incomplete and predict that fraternal relative deprivation can impair well-being if it is enduring and difficult to ameliorate. As part of a longitudinal study of the German unification process, measures of egoistic relative deprivation, fraternal relative deprivation, life satisfaction, mental health, and protest were obtained on three occasions of measurement (1996, 1998, 2000) from a demographically heterogeneous sample of 1276 East German citizens. Model tests and parameter estimation were performed with LISREL. In line with our predictions, unique longitudinal effects of fraternal relative deprivation on well-being were identified. No longitudinal effect of fraternal relative deprivation on protest was identified. PMID- 22043893 TI - Parent-child conflict and psychological maladjustment: a mediational analysis with reciprocal filial belief and perceived threat. AB - Empirical research has shown that parent-child conflict is positively related to poor adjustment in adolescents; however, the underlying processes have not been adequately examined. To explore the possible mediating pathways, reciprocal filial belief and perceived threat were chosen to represent two likely mechanisms accounting for how parent-child conflict harms adolescents' perceptions of their relationship with their parents and their self-perceptions within their cognitive appraisal framework. The former operates by attenuating children's affection towards their parents and the latter by lowering their self-perceptions. This study also distinguishes internalizing from externalizing problems in order to examine whether lower reciprocal filial belief more strongly mediates the relation between conflict with parents and adolescents' externalizing problems and whether perceived threat more strongly mediates the relation between conflict with parents and adolescents' internalizing problems. Hypotheses are as follows: (1) the more parent-child conflict adolescents report, the less reciprocal filial belief they recognize, which, in turn, leads to more maladjustments, especially externalizing ones; (2) the more parent-child conflicts adolescents report, the more threat they perceive, which, in turn, leads to more maladjustments, especially internalizing ones. Participants consisted of 603 Taiwanese adolescents (226 males and 377 females) aged 15 to 19 (average age = 16.95; SD = 0.78). Structural equation modelling analyses confirmed the hypotheses. However, the three direct effects of conflict on internalizing problems, aggression, and deviant behaviour were still significant. In addition, a greater effect of the paternal than the maternal role on the link between conflict and attenuated reciprocal filial belief, and between perceived threat and internalizing problems, was identified. Implications for understanding the mediation processes responsible for all indirect effects, even the subsidiary ones, and the greater impact of conflict with the father than with the mother are discussed. Limitations of the study and considerations for future research are also addressed. La recherche empirique a indique que le conflit parent-enfant est positivement lie a une faible adaptation chez les adolescents; cependant, les processus sous-jacents n'ont pas ete adequatement examines. Pour explorer les trajectoires de mediation possibles, la croyance filiale reciproque et la menace percue ont ete selectionnees afin de representer deux mechanismes plausiblement responsables de comment le conflit parent-enfant nuit aux peceptions des adolescents de leur relation avec les parents ainsi que de leurs auto-perceptions dans le cadre de leur evaluation cognitive. Le premier fonctionne en attenuant l'affection des enfants envers leurs parents et le dernier fonctionne en diminuant leurs auto-perceptions. Cette etude distingue aussi les problemes internalises de ceux qui sont externalises dans le but d'examiner si la plus faible croyance de filiation reciproque medie fortement la relation entre le conflit avec les parents et les problemes externalises des adolescents et si la menace percue medie plus fortement la relation entre le conflit avec les parents et les problemes internalises des adolescents. Les hypotheses sont les suivantes: (1) plus il y a de conflit parent-enfant rapporte par les adolescents, moins il y aura de croyance filiale reciproque reconnue par les adolescents qui, en revanche, menera a plus de mesadaptation surtout externalisee. L'echantillon incluait 603 participants (226 males et 377 femelles) ages entre 15 et 19 ans (age moyen = 16.95; SD = 0.78). Une analyse de modelisation par equation structurelle a confirme les hypotheses. Cependant, les trois effets directs du conflit sur les problemes internalises, sur l'agression et sur le comportement deviant etaient toujours significatifs. De plus, nous avons observe un plus grand effet du role paternel plus que maternel sur le lien entre le conflit et la croyance filiale reciproque attenuee ainsi qu'entre la menace percue et les problemes internalises. Les implications pour la comprehension des processus de mediation responsables pour tous les effets indirects, meme ceux qui sont accessoires, et le plus grand impact du conflit avec le pere plus qu'avec la mere sont discutes. Les limites de l'etude et les considerations pour la recherche future sont aussi abordees. La investigacion empirica ha demostrado que el conflicto entre padres e hijos esta positivamente relacionado con pobre ajuste en adolescentes; no obstante, el proceso subyacente no ha sido examinado adecuadamente. Para explorar posibles caminos, se eligieron la creencia filial reciproca y la amenaza percibida con el objetivo de representar dos posibles mecanismos explicativos de como el conflicto padres-hijos dana la percepcion de los adolescentes de su relacion con los padres y su auto-percepcion dentro de su marco de valoracion cognitiva. El primero actua atenuando el afecto de los hijos hacia los padres y el ultimo bajando su auto-percepcion. Este estudio tambien distingue los problemas interiorizados de los exteriorizados para examinar si la baja creencia filial reciproca es un mediador mas fuerte de la relacion entre el conflicto con los padres y los problemas exteriorizados de los adolescentes y si la amenaza percibida es un mediador mas fuerte de la relacion entre el conflicto con los padres y los problemas interiorizados de los adolescentes. Se han planteado las siguientes hipotesis: (1) cuanto mas conflicto entre padres e hijos refieran los adolescentes, menor sera el reconocimiento de la creencia filial reciproca, lo cual llevara a inadaptacion, sobre todo, exteriorizada; (2) cuanto mas conflicto entre padres e hijos refieran los adolescentes, mayor sera la amenaza percibida, lo cual llevara a mayor inadaptacion, sobre todo interiorizada. La muestra consistio de 603 adolescentes taiwaneses (226 chicos y 377 chicas) entre 15 y 19 anos de edad (media edad = 16.95; DT = 0.78). Los analisis de los modelos de ecuaciones estructurales confirmaron las hipotesis. Sin embargo, los tres efectos directos de los conflictos en la internalizacion de los problemas, agresion y comportamiento anormal seguian siendo significativos. Ademas, se identifico un efecto mayor del rol paternal en comparacion con el rol maternal en la relacion entre conflicto y la creencia filial reciproca atenuada y entre la amenaza percibida y la internalizacion de los problemas. Se discuten las implicaciones para la comprension del proceso mediador responsable de todos los efectos indirectos, incluso los subsidiarios, y el mayor impacto del conflicto con los padres que con las madres. Igualmente, se discuten las limitaciones del estudio y las consideraciones para la investigacion futura. PMID- 22043894 TI - Comparison of dysfunctional attitudes and social adjustment among infertile employed and unemployed women in Iran. AB - This study aims to compare dysfunctional attitudes and social adjustment in infertile employed and unemployed females. Due to the stresses of infertility, infertile females are faced with a variety of sexual and psychological problems, as well as dysfunctional attitudes that can lead to depression. Moreover, infertility problems provoke women into maladjustment and inadvertent corruption of relationships. In this regard, our goal is to consider the effects of employment in conjunction with education on dysfunctional attitudes and social adjustment among infertile women in Iran. In this work, we employed the survey method. We recruited 240 infertile women, utilizing the cluster random sampling method. These women filled out the Dysfunctional Attitudes Scale and the social adjustment part of the California Test of Personality. Next, multivariate analysis of variance was performed to test the relationship of employment status and education with dysfunctional attitudes and social adjustment. Our results indicated that dysfunctional attitudes were far more prevalent in infertile unemployed women than in infertile employed women. Also, social adjustment was better in infertile employed women than in infertile unemployed women. It was shown that education level alone does not have significant effect on dysfunctional attitudes and social adjustment. However, we demonstrated that the employment status of infertile women in conjunction with their education level significantly affects the two dimensions of dysfunctional attitudes (relationships, entitlements) and has insignificant effects on social adjustment. It was revealed that in employed infertile women in Iran, the higher education level, the less dysfunctional were attitudes in relationships and entitlements, whereas in unemployed infertile women, those with a college degree had the least and those with master's or higher degrees had the most dysfunctional attitudes in terms of relationships and entitlements. PMID- 22043895 TI - Comparative analysis of integrative self-knowledge, mindfulness, and private self consciousness in predicting responses to stress in Iran. AB - Previous research has established that awareness of self-experience is a stress resistance resource. The present study conducted an analysis of measures that record different aspects of self-awareness (private self-consciousness, mindfulness, and integrative self-knowledge) to explain this stress-resistance effect in a sample of Iranian university students (N = 186). These students responded to Mindfulness Attention Awareness, Private Self-Consciousness, Integrative Self-Knowledge, and Perceived Stress Scales just before the stress of a 20-day final examination period, and they then responded to Symptom Checklist and Vitality measures at four-day intervals during the final examinations. Prior to final examinations, the three self-awareness variables correlated positively with each other and negatively with perceived stress. Regression analyses of the data obtained during final examinations identified mindfulness to be a better operationalization of this stress-resistance resource than private self consciousness. Specifically, mindfulness but not private self-consciousness was a positive predictor of vitality and a negative predictor of symptoms. Hierarchical regression analyses also demonstrated that mindfulness and integrative self knowledge both explained resistance to physical symptoms, while integrative self knowledge functioned as a protective factor toward one's vitality. These data confirm the positive impact that self-awareness has during stress and highlight the importance of considering both mindfulness and integrative self-knowledge in understanding stress-resistance processes. PMID- 22043896 TI - Psychology through international congresses: differences between regions, countries, and congresses. AB - A published database of presentations from the seven most recent International Congresses of Applied Psychology (ICAPs) was compared to a similar but unpublished database (Adair, Anguas-Plata, Unik, & Radons, 2009) on the International Congresses of Psychology (ICPs) for the years 1996-2004. Analyses revealed phenomena characteristic of attendance at both international congresses: Participation rates spike dramatically for host countries; less dramatic regional surges in participation occur when the congress is held in a neighbouring country. Psychologists from 117 different countries participated in the seven recent congresses (ICAP and ICP) from 1994 to 2006. Overall ICP was double the size of ICAP, and represented a larger set of countries at each of its congresses. Regardless of location, most participants at both congresses came from the same 11 economically advantaged and seven majority-world countries. Congress presentations are dispersed across a much larger number of countries than are journal publications. The USA, for example, had modest 14.4% (ICAP) and 11.6% (ICP) presentation rates, much smaller than its majority share of publications (Adair, 2009 ). By contrast, the USA had the greater share of invited addresses at both ICAP (33.7%) and ICP (28.9%) congresses. Nonetheless, the majority-world countries contributing to both ICAP and ICP are clearly indicative of where the discipline is gaining strength and importance to international psychology. The emergence of Iran as a new leading national contributor to the two most recent international congresses, and the rise in the proportion of presentations by majority-world psychologists at ICAPs from only about one in five to more than one of every three presentations in recent congresses are findings consistent with Zakaria's (2008) analysis of changes taking place in the world. Within international congresses, certainly, the "rise of the rest" is changing the face of international psychology. PMID- 22043897 TI - 'Living a life in shades of grey': experiencing depressive symptoms in the acute phase after stroke. AB - AIM: The aim of the present study was to describe the lived experience of stroke survivors suffering from depressive symptoms in the acute phase; addressing the following questions: (a) what is the nature of depression as experienced by post stroke patients in the acute phase? (b) what is it like to live with depression within the first weeks following stroke? BACKGROUND: Post-stroke depression occurs in at least one quarter of stroke survivors and is linked to poorer outcomes. METHOD: This qualitative study is methodologically grounded in hermeneutic phenomenology, influenced by van Manen and Ricoeur. A descriptive, qualitative design was used applying in-depth interviews as the method of data collection with nine participants. The data collection took place in 2008. RESULTS: The material revealed two main themes that generate the feeling and description of 'living a life in shades of grey': (a) being trapped and (b) losing oneself. 'Shades of grey' could be understood as being confined in a new life-world and losing oneself as the person one knew. CONCLUSION: The participants confirmed suffering from depressive symptoms, but depression was not seen as meaningful on its own. They related their experiences of post-stroke depression in the acute phase to the losses they experienced. Nurses ought to take into account the depth of the life changes that stroke survivors may experience. There is a need for continued empirical research on how nurses may help and support stroke survivors dealing with depressive symptoms in the acute phase after stroke and how depressive symptoms develop over time. PMID- 22043898 TI - Dental fear in children with a cleft lip and/or cleft palate. AB - OBJECTIVE: To assess the level of dental fear in children with a cleft lip and/or palate, to compare this level with that of a normative group testing the hypothesis that children with a cleft lip and/or palate have a higher level of dental anxiety than children from the general population, and to assess the relation between dental fear and coping. DESIGN: Cross-sectional study. SETTING: VU Medical Centre University Amsterdam. PATIENTS: A total of 110 children (4 to 12 years old, 50 girls) with a cleft lip and/or palate. INTERVENTIONS: Dental fear in the study group was compared with a normative group of Dutch children. MAIN OUTCOME MEASURES: Dental fear was investigated using the parental version of the dental subscale of the Children's Fear Survey Schedule for children aged 4 and 5 years old (n = 36). Also the Inventory of Stressful Situations was completed. Children aged 6 to 12 years old also completed the Dental Cope Questionnaire. RESULTS: Young children with a cleft lip and/or palate experience more dental fear compared with children in a normative control group (Children's Fear Survey Schedule dental subscale scores: 30.3 +/- 14.6 compared with 24.6 +/- 8.6, p < .01). A weak correlation was found between the child's dental anxiety (Children's Fear Survey Schedule dental subscale) and his or her coping behavior (Dental Coping Questionnaire) (r = .196 p < .05). A clear correlation exists between the total Inventory of Stressful Situations and total Children's Fear Survey Schedule scores of the youngest age group (r = .507 p < .01). CONCLUSIONS: Findings support the hypothesis that dental anxiety is related to a higher level of exposure to medical interventions at a young age. PMID- 22043900 TI - Interleukin-32 enhances cytotoxic effect of natural killer cells to cancer cells via activation of death receptor 3. AB - Studies have demonstrated that the anti-tumour effect of natural killer (NK) cells is successful for patients with several cancers. Although interleukin-32 (IL-32) is endogenously expressed in NK cells, cytolytic function of NK cells against cancer cells has not been fully demonstrated. In the present study, we found that the growth of cancer cells was suppressed when colon cancer cells or prostate cancer cells were co-cultured with NK-92 cells, an NK cell line. We also found that the expression of tumour necrosis factor receptor 2 and death receptor 3 (DR3) was increased in PC3 cells, and the expression of FAS and DR3 was increased in SW620 cells by co-culture with NK-92 cells. However, cancer cell growth inhibition and IL-32 expression were abolished when cancer cells were co cultured with NK cells transfected with small interfering (si) RNA of IL-32. DR3 expression was also diminished by co-culture with IL-32-specific siRNA transfected NK-92 cells. Expression of APO3L, a ligand of DR3, was elevated in NK cells that were co-cultured with cancer cells. It was also found that expression of apoptosis-related proteins such as cleaved caspase-3 and bax was increased in cancer cells co-cultured with NK-92 cells, but their expression was abolished by co-culture with IL-32 siRNA-transfected NK-92 cells. Moreover, knockdown of DR3 in co-culture of NK-92 cells with cancer cells by siRNA or antibodies of DR3 and APO3L reversed the growth inhibitory effect of NK-92 cells. In conclusion, our study showed that IL-32 enhanced the cytotoxic effect of NK-92 cells on the cancer cells through activation of DR3 and caspase-3. PMID- 22043901 TI - Coexistence of two kinds of fluorinated hydrogenated micelles as building blocks for the design of bimodal mesoporous silica with two ordered mesopore networks. AB - A simple and effective route has been developed for the synthesis of bimodal (3.6 and 9.4 nm) mesoporous silica materials that have two ordered interconnected pore networks. Mesostructures have been prepared through the self-assembly mechanism by using a mixture of polyoxyethylene fluoroalkyl ether and triblock copolymer as building blocks. The investigation of the R(F)(8)(EO)(9)/P123/water phase diagram shows that in the considered surfactant range of concentrations the system is micellar (L(1)). DLS measurements indicate that this micellar phase is composed of two types of micelles; the size of the first one at around 7.6 nm corresponds unambiguously to the pure fluorinated micelles. The second type of micelles at higher diameter consists of fluorinated micelles that have accommodated a weak fraction of P123 molecules. Thus, in this study the bimodal mesoporous silica is really templated by two kinds of micelles. PMID- 22043902 TI - Postpartum rectal adenocarcinoma in a 26-year-old woman. PMID- 22043903 TI - Metal-organic frameworks based on unprecedented trinuclear and pentanuclear metal tetrazole clusters as secondary building units. AB - Solvothermal reactions of manganese(II) chloride tetrahydrate with a bis tetrazole ligand, 2,6-di(1H-tetrazol-5-yl)naphthalene (H(2)NDT), in N,N' dimethylformamide (DMF)/MeOH mixed solvent at two slightly different temperatures, 75 and 100 degrees C, led to two different metal-organic frameworks (MOFs), [Mn(II)(3)O(HNDT)(2)(NDT)(DMF)(3)] (1) and [Mn(II)(5)O(2)(HNDT)(2)(NDT)(2)(DMF)(8)] (2), with different net topologies. Single-crystal X-ray diffraction studies reveal that 1 is constructed from an unprecedented trinuclear building block, [Mn(II)(3)O(CN(4))(6)], as a 6-connected trigonal prismatic secondary building unit (SBU) of topological D(3h) site symmetry, and that the ligand in the HNDT(-1)/NDT(2-) deprotonation states is a linker, where two tetrazole (CN(4)) groups of the ligand are connected via a rigid naphthyl group. The tetrazole groups in 1 adopt a 1,2-MU-bridging mode with the manganese(II) ions to form a MU(3)-oxo trinuclear SBU. The trigonalprismatic SBU in 1 is connected to six neighboring SBUs to form a three-dimensional MOF of acs net topology. 2 is constructed from an unprecedented pentanuclear building block, [Mn(II)(5)O(2)(CN(4))(8)], as an 8-connected tetragonal prismatic SBU of topological D(4h) site symmetry. The tetrazole groups in 2 adopt monodentate, 1,2 MU- and 2,3-MU-bridging bidentate and 1,2,3-MU-bridging tridentate binding modes with the manganese(II) centers to form a bis-MU(3)-oxo pentanuclear SBU of local C(2) site symmetry. The tetragonal prismatic SBU in 2 is connected to eight neighboring SBUs to form a 3-D MOF of bcu net topology. PMID- 22043904 TI - Severe glomerulonephritis and encephalopathy associated with parvovirus B19 infection mimicking systemic lupus erythematosus. PMID- 22043905 TI - Preface. Prion research in perspective III. PMID- 22043906 TI - Generalization of the prion hypothesis to other neurodegenerative diseases: an imperfect fit. AB - Protein misfolding diseases have been classically understood as diffuse errors in protein folding, with misfolded protein arising autonomously throughout a tissue due to a pathologic stressor. The field of prion science has provided an alternative mechanism whereby a seed of pathologically misfolded protein, arising exogenously or through a rare endogenous structural fluctuation, yields a template to catalyze misfolding of the native protein. The misfolded protein may then spread intercellularly to communicate the misfold to adjacent areas and ultimately infect a whole tissue. Mounting evidence implicates a prion-like process in the propagation of several neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and the tauopathies. However, the parallels between the events observed in these conditions and those in prion disease are often incomplete. The aim of this review was to examine the current state of knowledge concerning the mechanisms of protein misfolding and aggregation for neurodegeneration-associated proteins. In addition, possible methods of intercellular spread are described that focus on the hypothesis that released microvesicles function as misfolded protein delivery vehicles, and the therapeutic options enabled by viewing these diseases from the prion perspective. PMID- 22043907 TI - Upregulation of micro RNA-146a (miRNA-146a), a marker for inflammatory neurodegeneration, in sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann Straussler-Scheinker (GSS) syndrome. AB - A mouse- and human-brain-abundant, nuclear factor (NF)-kB-regulated, micro RNA 146a (miRNA-146a) is an important modulator of the innate immune response and inflammatory signaling in specific immunological and brain cell types. Levels of miRNA-146a are induced in human brain cells challenged with at least five different species of single- or double-stranded DNA or RNA neurotrophic viruses, suggesting a broad role for miRNA-146a in the brain's innate immune response and antiviral immunity. Upregulated miRNA-146a is also observed in pro-inflammatory cytokine-, Abeta42 peptide- and neurotoxic metal-induced, oxidatively stressed human neuronal-glial primary cell cocultures, in murine scrapie and in Alzheimer's disease (AD) brain. In AD, miRNA-146a levels are found to progressively increase with disease severity and co-localize to brain regions enriched in inflammatory neuropathology. This study provides evidence of upregulation of miRNA-146a in extremely rare (incidence 1-10 per 100 million) human prion-based neurodegenerative disorders, including sporadic Creutzfeldt Jakob disease (sCJD) and Gerstmann-Straussler-Scheinker syndrome (GSS). The findings suggest that an upregulated miRNA-146a may be integral to innate immune or inflammatory brain cell responses in prion-mediated infections and to progressive and irreversible neurodegeneration of both the murine and human brain. PMID- 22043908 TI - Development of monoclonal antibodies specific for glycated prion protein. AB - Transmissive spongiform encephalopathies (TSE) are neurodegenerative diseases characterized by depositions of abnormally folded prion protein (PrP(TSE)) in brain. PrP(TSE) is at present the only specific biochemical marker of human and animal TSE. As deposits of PrP(TSE) remain in the body for long periods, there is substantial chance of them being nonenzymatically modified by glycation. The detection of glycated PrP(TSE) may have potential to serve as a diagnostic marker. Monoclonal antibodies specific for carboxymethyl lysine/arginine-modified prion protein were prepared. Recombinant human prion protein (rhPrP) was bacterially expressed and purified by affinity chromatography. rhPrP was modified by glyoxylic acid that introduces carboxymethyl groups on lysine and arginine residues present within the molecule of the protein. Modified rhPrP (rhPrP-CML) was used for immunization of 6 mice, and 960 hybridoma cells were prepared. Screening of cell supernatants resulted in the selection of four promising clones. One of them (EM-31) strongly reacts with human and mouse recombinant PrP CML, and three other clones react also with CML in vitro modified human and mouse brain PrP. Besides possible implication in TSE diagnostics, the antibodies may serve as tolls to advance our knowledge regarding the role of glycation in the prion pathophysiology. PMID- 22043909 TI - An NMR metabolomics study of elk inoculated with chronic wasting disease. AB - Chronic wasting disease (CWD) is a fatal neurodegenerative disease affecting both farmed and wild cervids, specifically deer and elk, and is a member of the larger family of prion diseases. Prion disease transmission is believed to occur through exposure to infectious prion material-a misfolded and infectious form of the prion protein that is normally present in the host. Chronic wasting disease is endemic to regions of central North America and infectious material can persist for long periods in the environment, posing challenges for remediation and monitoring. The current methods of detection are relatively invasive, require the host animal to be in intermediate to late stages of disease incubation, and are not without risk to those collecting samples. The potential for a blood test that could identify key biomarkers of disease incubation is of great interest. Serum from elk (Cervus elaphus) (n = 4) was collected on a monthly schedule before, and following, oral inoculation of CWD-positive homogenate, and collection continued until clinical signs were apparent. Blood was collected on the same schedule for a group of control animals (n = 2) housed under identical conditions. Targeted profiling, using (1)H-nuclear magnetic resonance (NMR) spectroscopy, of serum metabolites was used to yield metabolite identification as well as quantitation. Hierarchical multivariate statistical orthogonal partial least-squares (O-PLS) models were generated to identify predictive components in the data. Due to the duration of the study (25 mo) a significant aging component was taken into account during analysis. Several metabolites were correlated with aging in elk inoculated with CWD, but not in the control group. PMID- 22043910 TI - Alkylating antitumor drug mechlorethamine conceals a structured PrP domain and inhibits in vitro prion amplification. AB - Prion diseases are a group of incurable transmissible neurodegenerative disorders. The key molecular event in the pathogenesis of prion diseases is the conversion of the cellular prion protein (PrP(C)) into its pathological isoform (PrP(Sc)), accompanied by a conformational transition of alpha-helix into beta sheet structure involving the structured alpha-helix 1 domain from residues 144 154 of the protein (PrP144-154). Blocking the accessibility of PrP144-152 with anti-PrP antibody 6H4 was found to prevent PrP conversion and even to cure prion infection in cell models ( Enari et al. 2001 ). Previously, Yuan et al. (2005 ) demonstrated that the reduction and alkylation of PrP induced concealment of the 6H4 epitope. This study examined the ability of mechlorethamine (MCT), an alkylating antitumor drug, to conceal the 6H4 epitope and block PrP conversion in the presence of a reducing reagent. Mechlorethamine treatment significantly decreased in vitro amplification of PrP(Sc) in the highly efficient protein misfolding cyclic amplification system. Our findings suggest that MCT may serve as a potential therapeutic agent for prion diseases. PMID- 22043911 TI - Transcriptional modulation in a leukocyte-depleted splenic cell population during prion disease. AB - Prion replication in the periphery precedes neuroinvasion in many experimental rodent scrapie models, and in natural sheep scrapie and chronic wasting disease (CWD) in cervids. Prions propagate in the germinal centers of secondary lymphoid organs and are strongly associated with follicular dendritic cells (FDC) and possibly circulating dendritic cells and macrophages. Given the importance of lymphoid organs in prion disease transmission and pathogenesis, gene expression studies may reveal host factors or biological pathways related to prion replication and accumulation. A procedure was developed to enrich for FDC, dendritic cells, and macrophages prior to the investigation of transcriptional alterations in murine splenic cells during prion pathogenesis. In total, 1753 transcripts exhibited fold changes greater than three (false discovery rates less than 2%) in this population isolated from spleens of prion-infected versus uninfected mice. The gene for the small leucine-rich proteoglycan decorin (DCN) was one of the genes most overexpressed in infected mice, and the splenic protein levels mirrored this in mice infected with scrapie as well as bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (vCJD). A number of groups of functionally related genes were also significantly decreased in infected spleens. These included genes related to iron metabolism and homeostasis, pathways that have also been implicated in prion pathogenesis in the brain. These gene expression alterations provide insights into the molecular mechanisms underlying prion disease pathogenesis and may serve as a pool of potential surrogate markers for the early detection and diagnosis of some prion diseases. PMID- 22043912 TI - Diversity and distribution of white-tailed deer mtDNA lineages in chronic wasting disease (CWD) outbreak areas in southern Wisconsin, USA. AB - Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy affecting North American cervids. Because it is uniformly fatal, the disease is a major concern in the management of white-tailed deer populations. Management programs to control CWD require improved knowledge of deer interaction, movement, and population connectivity that could influence disease transmission and spread. Genetic methods were employed to evaluate connectivity among populations in the CWD management zone of southern Wisconsin. A 576-base-pair region of the mitochondrial DNA of 359 white-tailed deer from 12 sample populations was analyzed. Fifty-eight variable sites were detected within the sequence, defining 43 haplotypes. While most sample populations displayed similar levels of haplotype diversity, individual haplotypes were clustered on the landscape. Spatial clusters of different haplotypes were apparent in distinct ecoregions surrounding CWD outbreak areas. The spatial distribution of mtDNA haplotypes suggests that clustering of the deer matrilineal groups and population connectivity are associated with broad-scale geographic landscape features. These landscape characteristics may also influence the contact rates between groups and therefore the potential spread of CWD; this may be especially true of local disease spread between female social groups. Our results suggest that optimal CWD management needs to be tailored to fit gender-specific dispersal behaviors and regional differences in deer population connectivity. This information will help wildlife managers design surveillance and monitoring efforts based on population interactions and potential deer movement among CWD-affected and unaffected areas. PMID- 22043913 TI - Using linked household-level data sets to explain consumer response to bovine spongiform encepalopathy (BSE) in Canada. AB - Household-level Canadian meat purchases from 2002 to 2008 and a Food Opinions Survey conducted in 2008 were used to explore consumer responses to bovine spongiform encephalopathy (BSE) at the national level in Canada. Consumption in terms of the number of unit purchases was analyzed with a random-effects negative binomial model. In this study, household heterogeneity in meat purchases was partially explained using data from a self-reported food opinions survey. Of special interest was the hypothesis that consumers responded consistently to BSE in a one-time survey and in actual meat purchase behavior spanning years. Regional differences appeared, with consumers in eastern Canada reacting most negatively to BSE. Consumers responded more to the perception that food decision makers are honest about food safety than to the perception that they are knowledgeable, in maintaining beef purchases during BSE events. PMID- 22043914 TI - The role of psychological determinants and demographic factors in consumer demand for farm-to-fork traceability systems. AB - Traceability systems are an important tool (1) for tracking, monitoring, and managing product flows through the supply chain for better efficiency and profitability of suppliers, and (2) to improve consumer confidence in the face of serious food safety incidents. After the global bovine spongiform encephalopathy (BSE) crisis affected producers, consumers, trade, and the health status of animals and humans, new systems to help confirm the status of cattle products along the supply chain from farm to fork were implemented in many countries (Trautman et al. 2008 ). In this study, people's overall food safety beliefs are explored with the main objective of measuring the link between their food safety beliefs and their attitudes toward traceability. A comparison is made among English-speaking Canadians, French-speaking Canadians, and Japanese consumers. In the study, an Internet-based survey was used to collect data from nationally representative samples of the population in Canada-English (1275), Canada-French (343), and Japanese (1940) in the summer of 2009. Respondents' interests in traceability systems are clearly linked to their sense that the industry is primarily responsible for any food safety outbreaks. Moreover, it is clear that certain segments of the population in all samples feel strongly about the importance of farm to fork traceability in beef; thus, policymakers may wish to consider extending traceability beyond the point of slaughter as a way of encouraging beef sales in Canada. PMID- 22043915 TI - Do beef risk perceptions or risk attitudes have a greater effect on the beef purchase decisions of Canadian consumers? AB - Cluster analysis is applied in this study to group Canadian households by two characteristics, their risk perceptions and risk attitudes toward beef. There are some similarities in demographic profiles, meat purchases, and bovine spongiform encephalopathy (BSE) media recall between the cluster that perceives beef to be the most risky and the cluster that has little willingness to accept the risks of eating beef. There are similarities between the medium risk perception cluster and the medium risk attitude cluster, as well as between the cluster that perceives beef to have little risk and the cluster that is most willing to accept the risks of eating beef. Regression analysis shows that risk attitudes have a larger impact on household-level beef purchasing decisions than do risk perceptions for all consumer clusters. This implies that it may be more effective to undertake policies that reduce the risks associated with eating beef, instead of enhancing risk communication to improve risk perceptions. Only for certain clusters with higher willingness to accept the risks of eating beef might enhancing risk communication increase beef consumption significantly. The different role of risk perceptions and risk attitudes in beef consumption needs to be recognized during the design of risk management policies. PMID- 22043916 TI - Consumers' understanding and concerns about bovine spongiform encephalopathy (BSE): comparison among Canadian, American, and Japanese consumers. AB - In spite of much analysis of the impact of bovine spongiform encephalopathy (BSE) on consumer perceptions and meat purchases, there has been little explicit analysis of the level of BSE knowledge. In this study the role of knowledge about BSE was examined in Canada, the United States, and Japan. In addition, the level of knowledge was linked to human health concerns regarding BSE and whether there is agreement with paying a premium for beef with BSE animal tests. From a public policy perspective, understanding whether higher or lower knowledge is linked to public concern and desire for market intervention might help in the design of risk communication in any future animal disease outbreak. Should lack of knowledge about the disease be related to a public desire for market intervention (animal testing, for example), then an increase in detailed information about how humans might contract the disease might change public pressure for intervention. As compared to U.S. and Canadian respondents, Japanese respondents are more knowledgeable regarding the ways in which humans might be exposed to the human variant of BSE (variant Creutzfeldt-Jakob disease, vCJD) and are more concerned about the disease. However, U.S. respondents are more willing to pay a premium for beef tested to ensure that it will not result in vCJD. Japanese respondents who are more knowledgeable about BSE are more concerned about the risk of BSE to human health. In Canada, subjects who are more knowledgeable about the ways in which humans attain vCJD are less concerned about the risk of BSE to human health. Knowledge of the ways in which humans develop vCJD does not significantly influence concerns about the risk of BSE to human health in the United States or willingness to pay for BSE-tested beef in any of the three countries. The links between knowledge and concerns about BSE and between knowledge and agreement with paying premiums for BSE-tested beef were estimated for each country using ordered probit regressions. PMID- 22043917 TI - The economic impacts of chronic wasting disease and bovine spongiform encephalopathy in alberta and the rest of Canada. AB - Input-output analysis was used to calculate the economic impacts from potential prion diseases outbreaks in Alberta and the rest of Canada. Both chronic wasting disease (CWD) and bovine spongiform encephalopathy (BSE) have the capacity not only to affect the farmed cervid and cattle industries, but also to impact all industries with direct and indirect links to these sectors. Cervid sector shocks yield small spillover effects on the economies of Alberta as well as that of all of Canada. In contrast, the cattle sector generates larger multiplier effects in both specifically Alberta region and all of Canada. The industries that consistently experience the largest impacts from prion disease outbreaks in both Alberta and remainder of Canada economic regions are agricultural sectors, mining and energy sectors, and industries dedicated to trade, transportation, and warehousing. PMID- 22043918 TI - The impact of chronic wasting disease and its management on hunter perceptions, opinions, and behaviors in Alberta, Canada. AB - The goal of this analysis was to identify changes in hunting behavior, satisfaction, and perceptions of risk in the presence of chronic wasting disease (CWD). Hunters completed an Internet survey containing direct questions regarding the impacts of CWD and gathering information about real and hypothetical hunting trips. Overall, hunters were satisfied with CWD management, and although certain behaviors were altered, the perceived risk by hunters did not seem to be high. A travel cost model was used to determine whether differences in trip frequencies might be observed in response to CWD. The largest variation in trips was between urban and rural hunters, with urban hunters being less averse to traveling but more averse to CWD and the management program of extra tags. PMID- 22043919 TI - Public risk perception of relaxation of transmissible spongiform encephalopathies (TSE) measures in Europe. AB - The so-called "TSE roadmap" was published by the European Commission on July 15, 2005. The transmissible spongiform encephalopathy (TSE) roadmap suggests relaxation of bovine spongiform encephalopathy (BSE) in cattle and other animal transmissible spongiform encephalopathies measures in the short, medium, and long term. According to the TSE roadmap, "Any relaxation of BSE measures following the scientific assessment should be initiated by an open discussion with all stakeholders and supported by a strong communication strategy" ( European Commission 2005 , 5). Bearing this in mind, a social scientific project was designed to (1) involve different stakeholder groups, governmental risk managers, and their scientific advisors and (2) obtain their perception of the TSE roadmap and of its implications for precautionary consumer protection in five European Union (EU) Member States. This study describes the risk perception and risk management of TSE in Europe as exemplified by the TSE roadmap. The following query guided the international comparative study: How is TSE risk perceived by four interviewed stakeholder groups in five studied countries? The risk perceptions of TSE of risk managers from the ministries in charge in Belgium, France, Germany, Italy, and the United Kingdom, as well as their scientific advisors and stakeholder groups, were determined. The stakeholder groups were from three different areas involved with TSE, including farmers, consumers, and the meat/food industry. The issue to be addressed is roadmapping an adequate instrument for stakeholder involvement and for risk decision making. PMID- 22043921 TI - Dialkylaluminum hydride-promoted cyclodimerization of silylated 1,3-enynes via skeletal rearrangement. AB - The dialkylaluminum hydride-promoted reaction of 1-silylalk-3-en-1-ynes gave symmetrical 1,2,3,5-tetrasubstituted benzenes as single regioisomers. The novel cyclodimerization via skeletal rearrangement can be rationalized by an unprecedented mechanism involving sequential hydroalumination, alkene isomerization, carboalumination, carbon-carbon bond cleavage, and retro hydroalumination. PMID- 22043920 TI - CD4+ T helper 2 cells--microbial triggers, differentiation requirements and effector functions. AB - Over the past 10 years we have made great strides in our understanding of T helper cell differentiation, expansion and effector functions. Within the context of T helper type 2 (Th2) cell development, novel innate-like cells with the capacity to secrete large amounts of interleukin-5 (IL-5), IL-13 and IL-9 as well as IL-4-producing and antigen-processing basophils have (re)-emerged onto the type 2 scene. To what extent these new players influence alphabeta+ CD4+ Th2 cell differentiation is discussed throughout this appraisal of the current literature. We highlight the unique features of Th2 cell development, highlighting the three necessary signals, T-cell receptor ligation, co stimulation and cytokine receptor ligation. Finally, putting these into context, microbial and allergenic properties that trigger Th2 cell differentiation and how these influence Th2 effector function are discussed and questioned. PMID- 22043922 TI - H ferritin gene silencing in a human metastatic melanoma cell line: a proteomic analysis. AB - Ferritin, the major intracellular iron-storage protein, is made of 24 subunits of two types, H and L. Besides regulating intracellular iron homeostasis, it has been found that ferritin, in particular the H subunit (FHC), is involved in different biological events such as cell differentiation and pathologic states (i.e., neurodegeneration and cancer). This study is aimed at investigating the whole-cell proteome of FHC-expressing and sh-RNA-silenced human metastatic melanoma cells (MM07(m)) in the attempt to identify and classify the highest number of proteins directly or indirectly controlled by the FHC. We identified about 200 differentially expressed proteins and classified them in clusters on the basis of their functions, as proteins involved in metabolic processes, cell adhesion, migration, and proliferation processes. Some of them have captured our attention because of their involvement in metabolic pathways related to tumor progression and metastasis. In vitro assays confirmed that the FHC-silenced MM07(m) cells are characterized by a decreased growth activity, a reduced invasiveness, and a reduced cell adhesion capability. Moreover, nude mice (CD1 nu/nu), subcutaneously injected with FHC-silenced MM07(m) cells, showed a remarkable 4-fold reduction of their tumor growth capacity compared to those who received the FHC-unsilenced MM07(m) counterpart. In conclusion, these data indicate that gene silencing technology, coupled to proteomic analysis, is a powerful tool for a better understanding of H ferritin signaling pathways and lend support to the hypothesis that specific targeting of this gene might be an attractive and potentially effective strategy for the management of metastatic melanoma. PMID- 22043923 TI - CD300a and CD300f differentially regulate the MyD88 and TRIF-mediated TLR signalling pathways through activation of SHP-1 and/or SHP-2 in human monocytic cell lines. AB - CD300a, a membrane protein expressed on myeloid lineages and specific subsets of CD4(+) T cells, has been reported to have inhibitory activities in cellular activation. However, the role of CD300a in Toll-like receptor (TLR) -mediated macrophage activation has not been investigated. The human monocytic cell lines THP-1 and U937 were stimulated with various TLR ligands after triggering of CD300a with specific monoclonal antibody. Interestingly, CD300a blocked TLR4 mediated and TLR9-mediated expression of pro-inflammatory mediators without affecting TLR3-mediated events. In contrast, CD300f, another member of the CD300 family, blocked the activation of cells induced by all TLR ligands. A transient transfection assay using luciferase reporter gene under the regulation of nuclear factor-kappaB binding sites indicated that co-transfection of CD300f blocked reporter expression induced by over-expression of both myeloid differentiation factor 88 (MyD88) and toll-interleukin 1 receptor-domain-containing adapter inducing interferon-beta (TRIF), whereas CD300a blocked only MyD88-induced events. Synthetic peptides representing immunoreceptor tyrosine-based inhibitory motifs of CD300a or CD300f mimicked the differential inhibition patterns of their original molecules. The use of various signalling inhibitors and Western blotting analysis revealed that TLR9/MyD88-mediated signalling was regulated mainly by SH2 containing tyrosine phosphatase 1 (SHP-1), which could be activated by CD300a or CD300f. In contrast, regulation of the TLR3/TRIF-mediated pathway required the combined action of SHP-1 and SHP-2, which could be accomplished by CD300f but not CD300a. These data indicate that CD300a and CD300f regulate the MyD88 and TRIF mediated TLR signalling pathways through differential activation of SHP-1 and SHP 2. PMID- 22043924 TI - Evaluation of antidiabetic and antioxidant potential of lupeol in experimental hyperglycaemia. AB - Oxidative stress, produced under diabetic conditions, is a possible cause of various forms of tissue damage. The concentrations of antioxidant enzymes in cases of diabetes are significantly decreased, with a concomitant increase in lipid peroxidation. In this study, lupeol, a phytoconstituent from Solanum xanthocarpum, is shown to suppress the progression of diabetes after 21 days. Lupeol treatment caused decreases in glycated haemoglobin, serum glucose and nitric oxide, with a concomitant increase in serum insulin level. Furthermore, treatment with lupeol also increased antioxidant levels, with a decrease in the level of thiobarbituric acid-reactive oxygen species. PMID- 22043925 TI - Virologic and clinical features of primary infection with human parvovirus 4 in subjects with hemophilia: frequent transmission by virally inactivated clotting factor concentrates. AB - BACKGROUND: Human parvovirus 4 (PARV4) is a newly discovered parvovirus prevalent in injecting drug users and other groups with histories of parenteral exposure including persons with hemophilia exposed to non-virally inactivated clotting factor concentrates. To investigate its potential ongoing transmission to persons with hemophilia treated with plasma-derived, virally inactivated clotting factors, we screened a large cohort of persons with hemophilia for antibody seroconversion to PARV4 over a 5-year observation period. STUDY DESIGN AND METHODS: Samples from 195 persons with hemophilia enrolled in the Hemophilia Growth and Development Study cohort were screened for PARV4 antibodies at the start and end of a 5-year period of treatment with exclusively virally inactivated clotting factor concentrates. Samples collected at intermediate time points from subjects seroconverting over the study period were screened to narrow down the seroconversion time and investigate immunoglobulin (Ig)M responses, duration of acute viremia, and clinical presentations. RESULTS: PARV4 seroprevalence at the outset of the study was 44%. Over the observation period, nine subjects (seven human immunodeficiency virus positive) seroconverted for anti-PARV4 (incidence, 1.7%/year). Infected subjects showed relatively prolonged durations of viremia (mean, 7 months) and weak, transient IgM responses during acute infections. Clotting factors inactivated by solvent/detergent or by wet or dry heat were infectious. The most common clinical presentations were rashes and exacerbation of hepatitis. CONCLUSION: This study identifies PARV4 as a transfusion-transmissible agent that is resistant to viral inactivation. Of concern, infections may still regularly occur in those exposed to plasma-derived blood products. Urgent evaluation of the incidence of PARV4 in treated individuals and disease associations of PARV4 infections is required. PMID- 22043926 TI - Plasma corticosterone elevation inhibits the activation of nuclear factor kappa B (NFKB) in the Syrian hamster pineal gland. AB - We evaluated how the mild stress-induced increase in endogenous corticosterone affected the pineal gland in Syrian hamsters (Mesocricetus auratus). The animals were maintained under constant light for 1 day, instead of a cycle of 14:10-h, to increase the circulating corticosterone levels during the daytime. The nuclear translocation of nuclear factor kappa B (NFKB), which is the pivotal transcription factor for stress and injury, presented a daily rhythm in normal animals. NFKB nuclear content increased linearly from the onset of light [Zeitgeber Time 0 (ZT0)] until ZT11 and decreased after ZT12 when the plasma corticosterone peak was detected in normal animals. However, the 24-h profiles of the two curves were different, and they did not clearly support an exclusive relationship between corticosterone levels and NFKB content. Therefore, we tested the effect of increased endogenous corticosterone through inducing mild stress by maintaining daytime illumination for one night. This stressful condition, which increased daytime corticosterone levels, resulted in a daytime decrease in NFKB nuclear content, and this was inhibited by mifepristone. Overall, this study shows that NFKB has a daily rhythm in Syrian hamster pineal glands and, by increasing endogenous corticosterone with a stressful condition, NFKB activity is regulated. Therefore, this study suggests that the pineal gland in the Syrian hamster is a sensor of stressful conditions. PMID- 22043927 TI - Titanium tert-butoxyimido compounds. AB - The synthesis and molecular and electronic structures of the first tert butoxyimido complexes of titanium (TiNO(t)Bu functional group) are reported, featuring a variety of mono- or poly-dentate, neutral or anionic N-donor ligands. Reaction of Ti(NMe(2))(2)Cl(2) with (t)BuONH(2) gave good yields of Ti(NO(t)Bu)Cl(2)(NHMe(2))(2) (1). Compound 1 serves as an excellent entry point into new tert-butoxyimido complexes by reaction with a variety of fac-N(3) donor ligands, namely, Me(3)[9]aneN(3) (trimethyl-1,4,7-triazacyclononane), HC(Me(2)pz)(3) (tris(3,5-dimethylpyrazolyl)methane), or Me(3)[6]aneN(3) (trimethyl-1,3,5-triazacyclohexane) to give Ti(NO(t)Bu)(Me(3)[9]aneN(3))Cl(2) (2), Ti(NO(t)Bu){HC(Me(2)pz)(3)}Cl(2) (3), or Ti(NO(t)Bu)(Me(3)[6]aneN(3))Cl(2) (4) in good yield. It was found that 4 could be converted into Ti(NO(t)Bu)Cl(2)(py)(3) (5) in very good yield by reaction with an excess of pyridine. Compound 5 is effective in a range of salt metathesis reactions with lithiated amide or pyrrolide ligands, and reacts with Li(2)N(2)N(py), Li(2)N(2)N(Me), LiN(pyr)N(Me(2)), or Li(2)N(2)(pyr)N(Me) to give Ti(N(2)N(py))(NO(t)Bu)(py) (6), Ti(N(2)N(Me))(NO(t)Bu)(py) (7), Ti(N(pyr)N(Me(2)))(NO(t)Bu)Cl(py)(2) (9), or Ti(N(2)(pyr)N(Me))(NO(t)Bu)(py)(2) (10) in moderate to good yields (N(2)N(py) = (2 NC(5)H(4))C(Me)(CH(2)NSiMe(3))(2); N(2)N(Me) = MeN(CH(2)CH(2)NSiMe(3))(2); N(pyr)N(Me(2)) = Me(2)NCH(2)(2-NC(4)H(3)); N(2)(pyr)N(Me) = MeN{CH(2)(2 NC(4)H(3))}(2)). Compounds 7, 9, and 10 reacted with 2,2'-bipyridyl by pyridine exchange reactions forming Ti(N(2)N(Me))(NO(t)Bu)(bipy) (8), Ti(N(pyr)N(Me(2)))(NO(t)Bu)Cl(bipy) (11), and Ti(N(2)(pyr)N(Me))(NO(t)Bu)(bipy) (12). Ten tert-butoxyimido compounds, namely, 1-6, 11, and 12, have been structurally characterized revealing approximately linear Ti-N-O(t)Bu linkages with Ti-N distances [range 1.686(2)-1.734(2) A] that are generally intermediate between those in the homologous alkylimido and phenylimido analogues, and shorter than in the diphenylhydrazido counterparts. Density functional theory (DFT) studies on the model compounds Ti(NR)Cl(2)(NHMe(2))(2) (1_R; R = OMe, Me, Ph, NMe(2)) confirmed this trend and found that the destabilizing effect of the -OMe oxygen 2p(pi) lone pair on one of the Ti-N pi-bonds in 1_OMe is comparable to that of the occupied phenyl ring pi orbitals in the phenylimido homologue 1_Ph but much less than for the -NMe(2) nitrogen lone pair in 1_NMe(2). PMID- 22043928 TI - Abdominal obesity and endometrial cancer in egyptian females with postmenopausal bleeding. AB - Endometrial cancer is the most common type of female genital tract malignancies. We intended to assess the relation between different measures of obesity and the risk to develop endometrial cancer in Egyptian females with postmenopausal bleeding (PMB). The study was conducted in Alexandria, Egypt and included all postmenopausal females presenting to the University Hospital of Gynecology and Obstetrics with PMB within the study period (from January 1 to September 30). A questionnaire was completed, and data about anthropometric measurements including weight, height, and waist circumference were collected. Vaginal sonography, dilatation and curettage, and pathological examination were done by experts for all participants. Endometrial cancer was diagnosed in 38% of females presenting with PMB. Using ROC curve analysis, only the measure of abdominal obesity (waist circumference) showed significant accuracy in predicting endometrial cancer (area = 0.63, P < .05). The best cutoff point that maximizes accuracy was 88 cm. Body mass index (>=30 vs. <=30) showed no significant relation (OR = 1.1, 95%CI 0.5 2.3), and the ratio between upper and lower body obesity (W/H ratio) showed border line significant relation (OR = 2, 95% CI 1-4.1), whereas waist circumference (>=88 vs. <=88 cm) showed strikingly high OR (OR = 13.6, 95%CI 4 46.6). The risk of abdominal obesity on endometrial cancer remains very high (OR = 15.8, 95%CI 4.1-60.9) even after adjustment, in a logistic model, for other risk factors such as age at presentation, age at menarche, age at menopause, family history of malignancy, and gravidity. Abdominal obesity (waist circumference >88 cm) is the best measure of obesity to be used in predicting the risk of endometrial cancer in Egyptian females with PMB. PMID- 22043929 TI - Cortisol and symptoms of psychopathology in Russian and American college students. AB - Cortisol is a key player in the hypothalamus-pituitary-adrenal (HPA) axis response to stress, and has been related to symptoms of depression and other stress-related pathology. The present study investigated the relationship between cortisol and survey measures of stress and psychopathology as well as lifestyle in Russian and American college students. Salivary cortisol was collected upon awakening, 30 min later, at 4 p.m., and at 10 p.m. by Russian and American college students. Survey measures of anxiety and depression, as measured by the Hopkins Symptom Checklist (HSCL-25) were collected as well as scores on the Trauma History Questionnaire (THQ). In addition, measures of drinking-related problems, as measured by the Alcohol Use Disorder Identification Test (AUDIT) and the "Cut down, Annoyed, Guilty, Eye-opener" (CAGE) were also completed. Consistent with the typically observed empirical pattern, cortisol levels increased in the 30 min after awakening and then declined across the day. Women reported more symptoms of anxiety than did men in both Russian and American samples. American students reported more symptoms of depression than did Russian students, though Russian students reported more traumatic life experiences. Americans had higher cortisol levels overall, though Russian students had larger changes in cortisol levels across the day, associated with both greater morning rises and afternoon declines in cortisol. While more Russian students reported smoking, American students reported more problems associated with alcohol use as measured by the AUDIT. The relationship between stress and health, mediating factors of lifestyle and coping, and the impact of social transition in Russia are discussed. PMID- 22043930 TI - Exercise interventions and their effects on physical self-perceptions of male university students. AB - The purpose of the present study was to examine the effects of 12-week exercise interventions on physical self-perceptions of male university students. The study also aimed to investigate the relationships between the changes in physical self perceptions and the changes in some physiological measures after 12-week exercise programs. Forty-eight male university students aged from 19 to 25 years were enrolled in this study. Participants were randomly and equally assigned to swimming, running, cycling and control conditions. The Physical Self-Perception Profile was administered to all participants before and after 12-week exercise programs. Additionally, strength, maximal oxygen uptake (VO(2max)) and body compositions were assessed before and after interventions. Participants in the exercise groups attended swimming, running or cycling sessions for 40 min per day, 3 days per week with 60-70% of their heart rate reserves, while those in the control group did not attend any regular physical activity. The results of 4 * 2 * 5 MANOVA with the dimensions of physical self-perceptions as within-subject factor revealed that all groups including the control group revealed better physical-self-perceptions from pre- to post-test. Results of 4 * 2 * 3 MANOVA with physiological measures as within-subject factor revealed that VO(2max) values of participants in the swimming group improved more than the other groups. On the other hand, no significant differences were observed in strength scores and body fat levels among groups. Furthermore, no significant associations were obtained between the changes in physical self-perception dimensions and the physiological measures. PMID- 22043931 TI - Perceived normative pressure and majority adolescents' implicit and explicit attitudes towards immigrants. AB - The aim of the present study was to examine if perceived normative pressure (i.e., perception of the normative expectations of family and friends regarding one's intergroup attitudes) had a direct impact on majority youth's (N = 93) explicit attitudes and moderated the relationship between their implicit (measured with the ST-IAT) and explicit attitudes towards Russian immigrants in Finland. The results indicated that normative pressure is positively associated with the explicit attitudes of adolescents, and that the implicit attitudes of the adolescents towards immigrants surface on the explicit level only when they do not perceive a normative pressure to hold positive intergroup attitudes. More specifically, when there is no normative pressure, the explicit attitudes of youth are, at best, neutral, and reflect their implicit attitudes. In contrast, when normative pressure is perceived to be high, the level of explicit attitudes is generally more positive, and the expression of explicit attitudes is not determined by implicit attitudes. The effects of age, sex, quality of past intergroup contact experiences, and intergroup anxiety were controlled for in the analysis. The findings highlight the importance of taking normative pressure into consideration when studying socially sensitive ethnic attitudes among adolescents. PMID- 22043932 TI - Regulatory focus and attitudes to migrants. AB - In two studies we examined the role of two regulatory foci (i.e., prevention and promotion) in predicting Australian's attitudes to different types of migrants. According to regulatory focus theory, promotion-focused self-regulation is concerned with nurturance and accomplishment needs and involves the pursuit of wishes and aspirations. As such, it results in sensitivity to positive outcomes and to relative pleasure from gains. On the other hand, prevention-focused self regulation is concerned with security needs and is directed at meeting duties and obligations. As such, it results in sensitivity to negative outcome and relative pain from losses. In Study 1, as predicted, the extent of promotion focus (i.e., a concern with accomplishment and the pursuit of ideals) predicted more positive attitudes to culturally similar and economically beneficial migrants, whereas the extent of prevention focus (i.e., concern with security and meeting obligations) predicted more negative attitudes to migrants who are culturally dissimilar. In Study 2 we replicated and extended these findings, showing that the extent of promotion focus and a lack of concern with threats predicted positive attitudes to both culturally similar and economically beneficial migrants, which, in the case of the latter group, was mediated by a focus on the benefits these migrants provide. In the case of culturally dissimilar migrants, the extent of promotion focus and a concern with gains predicted more positive attitudes. However, for economically less beneficial migrants, neither the extent of promotion nor prevention focus was a predictor. Only lower concerns with threat predicted more positive attitudes to this migrant group. The results are discussed with respect to other determinants of attitudes to migrants and the implications for migration and asylum-seeker policy. PMID- 22043933 TI - Gender moderates the impact of need for structure on social beliefs: implications for ethnocentrism and authoritarianism. AB - The present research examines the interplay between individual differences in need for structure, social beliefs, and gender. It is well documented that need for structure, that is, a preference for structure and simplicity in one's thinking, predicts authoritarianism and ethnocentrism. Further, women tend to score lower in authoritarianism and ethnocentrism than men. Although there seem to be no gender differences in need for structure, the present research hypothesizes that the association between need for structure and social beliefs is stronger for men than for women. This hypothesis comes from the observation that, all else being equal, men tend to think more about the domain of beliefs such as authoritarianism and ethnocentrism, which should strengthen the relationship between men's cognitive needs and their social beliefs. The hypothesis is also motivated by the finding that, more than men, women often give priority to caring and compassion when forming beliefs about outgroups. This should weaken the link between women's cognitive needs and their social beliefs. Three studies conducted in the USA (n = 398) and one study conducted in Germany (n = 112) examined whether gender moderated the influence of need for structure on authoritarianism and racism. Using a variety of measures, need for structure predicted authoritarianism and racism for men, but not for women. The discussion focuses on the implications of the present findings for the relationship between cognitive orientations and social beliefs. It is argued that research on cognitive orientation and social beliefs needs to take gender into account to improve its accuracy of prediction. PMID- 22043934 TI - Adolescents' evaluative beliefs of failure: explorations in a Chinese Singaporean sample. AB - Our study explored evaluative beliefs of failure to see whether positive and negative beliefs of failure are bivariate in nature within three domains of an adolescent's life (academic, social, and athletic) and how such beliefs are differentially linked to the importance of a domain, the frequency of failure in a domain, and the extremity of negative emotions experienced when encountering failure in a domain. A total of 163 Chinese Singaporean students in Secondary 3 and 4 (Grades 9 and 10) from two Singapore schools participated in the study by completing a questionnaire. Results from various analyses converged to demonstrate that evaluative beliefs could be distinguished by both valence (positive and negative) and domain (academic, social, and athletic). The six evaluative beliefs were also distinguished from failure attributions. While there was consensus in what constituted negative beliefs of failure across domains, positive beliefs of failure showed some domain specificity, with unique aspects in particular domains (e.g., the inevitability of failure only in the academic domain). Positive and negative beliefs in the different domains were correlated among themselves, but positive and negative beliefs were uncorrelated within (except for academic) and across domains. Positive and negative beliefs were also differentially linked to domain importance, failure frequency, and extremity of negative emotion. Unexpectedly, domain importance was not linked to negative beliefs but was linked to positive beliefs, while positive and negative beliefs showed domain-specific links with failure frequency. As expected, however, negative beliefs were (positively) linked to extremity of negative emotions while positive beliefs were not linked to such extremity. The conceptual, substantive, and practical implications of these results are discussed. PMID- 22043935 TI - Personal and general belief in a just world as judgement norms. AB - Research on the belief in a just world (BJW) has focused on its intra-individual functions (e.g., psychological well-being) and its inter-individual consequences (e.g., derogation of victims). Recent theorizing, however, has indicated that the BJW may also have more societal functions and consequences, serving as a legitimizing device of the status quo. The studies in the current paper focus on this latter view and are based on Alves and Correia's ( 2008 ) research which found that the expression of high personal and general belief in a just world is injunctively normative. Two experimental studies aimed at ascertaining three issues: (1) the dimension(s) of social value (social utility and/or social desirability) on which the BJW normativity anchors; (2) whether the expression of moderate BJW is also injunctively normative; and (3) whether the injunctive normativity of the BJW is related to perceptions of truth. Results indicate that moderate and high personal and general BJW are normative. Yet, whereas the normativity of personal BJW anchors both on social utility and social desirability, that of general BJW anchors only on social utility. We discuss personal and general BJW as judgement norms, whose normativity may not be personally acknowledged (in the case of general BJW) and does not necessarily derive from being perceived as true, but from the fact that such norms carry social value at least in individualistic societies. PMID- 22043936 TI - Public and private schoolteachers' differences in terms of job attitudes in Albania. AB - In the present study, the attitudinal differences between public and private schoolteachers in Albania were investigated. Since the type of the organization varies, one would expect different climates for the emergence of job attitudes- mainly job satisfaction, job involvement, and organizational commitment, the most frequently studied job attitudes in the industrial and organizational psychology literature. It was hypothesized that the private schoolteachers would be more satisfied than public schoolteachers, especially due to high levels of payment and other desirable conditions. However, the public schoolteachers will be more involved than the private schoolteachers since they have to justify their continued work under the undesirable conditions. The commitment level of the private schoolteachers will be higher than the public schoolteachers since there is usually high correlation between job satisfaction and organizational commitment. Data were gathered from a total of 429 teachers working in public (n = 254) and private (n = 175) schools in Albania, in high and middle schools. The data were analyzed using multivariate analysis of covariance with age as a covariate. The results indicated that the private schoolteachers were more satisfied, as expected, revealed a weaker job involvement and were more committed to their school than their colleagues in the public sector. The results were found to be in line with previous studies conducted in the west. However, this study is believed to have a potential contribution to the literature in general, and to the Albanian local literature in particular. To the knowledge of the authors, there has been no similar study in Albania. Discussion is provided along with the limitations of the study and suggestions for future research. PMID- 22043937 TI - Fabrication of reversible poly(dimethylsiloxane) surfaces via host-guest chemistry and their repeated utilization in cardiac biomarker analysis. AB - On the basis of the host-guest interactions between azobenzenes and cyclodextrins, a new strategy for the preparation of a dually functionalized poly(dimethylsiloxane) (PDMS) surface was investigated using surface-initiated atom-transfer radical polymerization (SI-ATRP) and click chemistry. The PDMS substrates were first oxidized in a H(2)SO(4)/H(2)O(2) solution to transform the surface Si-CH(3) groups into Si-OH groups. Then, the SI-ATRP initiator 3-(2 bromoisobutyramido)propyl(trime-thoxy)silane was grafted onto the substrates through a silanization reaction. Sequentially, the poly(ethylene glycol) (PEG) units were introduced onto the PDMS-Br surfaces via SI-ATRP reaction using oligo(ethylene glycol) methacrylate. Afterward, the bromide groups on the surface were converted to azido groups via nucleophilic substitution reaction with NaN(3). Finally, the azido-grafted PDMS surfaces were subjected to a click reaction with alkynyl and PEG-modified beta-cyclodextrins, resulting in the grafting of cyclodextrins onto the PDMS surfaces. The composition and chemical state of the modified surfaces were characterized via X-ray photoelectron spectroscopy, and the stability and dynamic characteristics of the cyclodextrin modified PDMS substrates were investigated via attenuated total reflection Fourier transform infrared spectroscopy and temporal contact angle experiments. The surface morphology of the modified PDMS surfaces was characterized through imaging using a multimode atomic force microscope. A protein adsorption assay using Alexa Fluor594-labeled bovine serum albumin, Alexa Fluor594-labeled chicken egg albumin, and FITC-labeled lysozyme shows that the prepared PDMS surfaces possess good protein-repelling properties. On-surface studies on the interactions between azobenzenes and the cyclodextrin-modified surfaces reveal that the reversible binding of azobenzene to the cyclodextrin-modified PDMS surfaces and its subsequent release can be reversibly controlled using UV irradiation. Sandwich fluoroimmunoassay of the cardiac markers myoglobin and fatty acid binding protein demonstrates that the cyclodextrin-modified PDMS surfaces can be repeatedly utilized in disease biomarker analysis. PMID- 22043938 TI - Re: Clinical periodontal and microbiologic parameters in patients with rheumatoid arthritis. PMID- 22043939 TI - Re: Association between periodontitis and hemorrhagic stroke among Koreans: a case-control study. PMID- 22043941 TI - Role of the inflammatory protein serine protease inhibitor Kazal in preventing cytolytic granule granzyme A-mediated apoptosis. AB - Serine protease inhibitor Kazal (SPIK) is an inflammatory protein whose levels are elevated in numerous cancers. However, the role of this protein in cancer development is unknown. We have recently found that SPIK suppresses serine protease-dependent cell apoptosis. Here, we report that anti-SPIK antibodies can co-immmunoprecipitate serine protease granzyme A (GzmA), a cytolytic granule secreted by cytotoxic T lymphocytes and natural killer cells during immune surveillance, and that SPIK suppresses GzmA-induced cell apoptosis. Deletion studies show that the C3-C4 region of SPIK is critical for this suppression. These studies suggest that over-expression of SPIK may prevent GzmA-mediated immune-killing, thereby establishing the tolerance of cancer cells to the body's immune surveillance system. Suppression of over-expressed SPIK can restore the susceptibility of these cells to apoptotic death triggered by GzmA. This finding implies that it is possible to overcome tolerance of cancer cells to the body's immune surveillance system and restore the GzmA-mediated immune-killing by suppressing the over-expression of SPIK. PMID- 22043942 TI - Controlling the wettability of hierarchically structured thermoplastics. AB - Surfaces play an important role in defining the properties of materials, controlling wetting, adsorption, or desorption of biomolecules, and sealing/bonding of different materials. We have combined microscale features with plasma-etched nanoscale roughness and chemical modification to tailor the wettability of the substrates. Cyclic olefin polymers and copolymers (COPs/COCs) were processed to make a range of surfaces with controlled superhydrophobic or hydrophilic properties. The hydrophobic properties of the polymers were increased by the introduction of microstructures of varying geometry and spacing through hot embossing. The COC/COP substrates were functionalized by plasma activation in O(2), CF(4), and a mixture of both gases. The plasma etching introduces nanoscale roughness and also chemically modifies the surface, creating either highly hydrophilic or highly hydrophobic (contact angle >150 degrees ) surfaces depending on the gas mixture. The influence of geometry and chemistries was characterized by atomic force microscopy, contact angle measurements, and X-ray photoelectron spectroscopy. Measurements of the contact angle and contact angle hysteresis demonstrated long-term stability of the superhydrophobic/superhydrophilic characteristics (>6 months). PMID- 22043943 TI - Subcomponent self-assembly and guest-binding properties of face-capped Fe4L4(8+) capsules. AB - A general method for preparing Fe(4)L(4) face-capped tetrahedral cages through subcomponent self-assembly was developed and has been demonstrated using four different C(3)-symmetric triamines, 2-formylpyridine, and iron(II). Three of the triamines were shown also to form Fe(2)L(3) helicates when the appropriate stoichiometry of subcomponents was used. Two of the cages were observed to have nearly identical Fe-Fe distances in the solid state, which enabled their ligands to be coincorporated into a collection of mixed cages. Only one of the cages combined a sufficiently large cavity with the sufficiently small pores required for guest binding, taking up a wide variety of guest species in size- and shape selective fashion. PMID- 22043944 TI - Association of 25-hydroxyvitamin D with the incidence of knee and hip osteoarthritis: a 22-year follow-up study. AB - OBJECTIVE: In the light of conflicting results from previous studies on the role of vitamin D, we studied serum 25-hydroxyvitamin D [25(OH)D] with regard to its prediction of incident knee and hip osteoarthritis (OA). METHODS: The study population (n = 805) consisted of participants of a national health examination survey who had undergone baseline and follow-up clinical examinations at intervals of 20-23 years. Knee and hip OA were diagnosed on the basis of a standardized clinical examination by physicians with the same diagnostic criteria at baseline and follow-up. Information on covariates, including age, sex, season of blood draw, education, body mass index (BMI), physical workload, leisure time physical activity, smoking history, and previous injuries, was collected at baseline. Serum 25(OH)D concentrations were determined from baseline serum samples kept frozen at -20 degrees C. RESULTS: We found no significant association between serum 25(OH)D level and the risk of incident knee or hip OA. However, a statistically significant interaction between season of blood draw and serum 25(OH)D emerged when predicting the development of definite knee OA (p = 0.004). After adjusting for all the covariates, the relative odds (95% confidence interval) of developing definite knee OA per increment of 1 SD (20.7 ng/mL) in winter season 25(OH)D was 1.57 (1.10-2.27), whereas for summer season sera the corresponding rate was 0.53 (0.28-1.00). CONCLUSION: The results do not support the hypothesis that a low level of serum 25(OH)D contributes to the development of OA. Instead, our study suggests that season is a potent effect modifier of 25(OH)D, which merits attention in future research. PMID- 22043946 TI - The Decade of Vaccines Collaboration: developing a global roadmap for saving lives. PMID- 22043947 TI - Pertussis vaccines: where to now? PMID- 22043949 TI - HPV vaccines: what remains to be done? Interview by Lauren Constable. PMID- 22043950 TI - A universal influenza vaccine: the BiondVax story. Interview by Paolo Reveglia. PMID- 22043951 TI - The seasonal influenza vaccine Agriflu((r)). AB - Seasonal influenza continues to have a large impact annually. Combined with pneumonia, influenza is the sixth leading cause of death in the USA, and vaccination has been the most important tool to prevent it. Agriflu((r)) is an egg-derived, subunit, nonadjuvanted trivalent inactivated vaccine indicated for immunization to prevent disease caused by influenza virus subtypes A and B contained in the vaccine. Agriflu was approved in the USA by the US FDA on 27 November 2009, for those aged 18 years and older, to prevent disease caused by influenza virus subtypes A and B. Based on clinical trial evidence, Agriflu has been shown to be safe, with <1% serious adverse event rates, and immunogenic. It has been proven to be highly effective to prevent culture-confirmed influenza and, thus, is an alternative to previously licensed seasonal influenza vaccines. Besides Fluvirin((r)), Agriflu is the only subunit vaccine available in the USA. Owing to the economic burden, morbidity and mortality caused by seasonal influenza, addition of new, safe and effective vaccines to the available tools, to reduce the impact of influenza, is of importance and benefit, especially in the face of the recent shortages of influenza vaccines. PMID- 22043952 TI - MF59TM-adjuvanted seasonal influenza vaccine in young children. AB - Influenza is a viral disease of the upper respiratory tract, which is manifested in seasonal epidemic waves associated with excess morbidity and mortality. Although efforts at prevention have traditionally been focused on the elderly, interest is growing on the specific features of influenza disease in children and the opportunities for prevention in this age group. Owing to recent improvements in surveillance schemes and diagnostic tools it has been realized that young children experience a burden of morbidity due to influenza as high or higher than the elderly and that children possibly act as a source of influenza infection and determinants of the intensity and the spread of influenza in the community, and as a result, the proposition that children should be preferentially targeted for influenza vaccination is gaining acceptance in many industrialized countries. Traditional seasonal inactivated influenza vaccines have performed poorly in the very young and the live-attenuated influenza vaccines, which are highly efficacious in this age group, have been associated with a poor safety profile in those less than 2 years of age. MF59TM-adjuvanted influenza vaccines that were traditionally used in the elderly show a very promising safety and efficacy profile in the pediatric population that could overcome the limitations of the other currently available influenza vaccines for use in this age group. PMID- 22043953 TI - Improving immunogenicity and effectiveness of influenza vaccine in older adults. AB - Aging is associated with a decline in immune function (immunosenescence) that leads to progressive deterioration in both innate and adaptive immune functions. These changes contribute to the subsequent increased risk for infectious diseases and their sequelae. Vaccination is the most effective and inexpensive public health strategy for prevention of infection, despite the decreased efficacy of vaccines in older adults due to immunosenescence. The rapid rise in the older adult population globally represents a great challenge for vaccination programs. This article first addresses the status of innate and adaptive immune functions in aging and then focuses on influenza vaccine. The development history of influenza vaccines, current status, and potential strategies to improve the immunogenicity and vaccine effectiveness in older adults are discussed. PMID- 22043954 TI - Adenovirus-vectored drug-vaccine duo as a potential driver for conferring mass protection against infectious diseases. AB - The disease-fighting power of vaccines has been a public health bonanza credited with the worldwide reduction of mortality and morbidity. The goal to further amplify its power by boosting vaccine coverage requires the development of a new generation of rapid-response vaccines that can be mass produced at low costs and mass administered by nonmedical personnel. The new vaccines also have to be endowed with a higher safety margin than that of conventional vaccines. The nonreplicating adenovirus-vectored vaccine holds promise in boosting vaccine coverage because the vector can be rapidly manufactured in serum-free suspension cells in response to a surge in demand, and noninvasively administered by nasal spray into human subjects in compliance with evolutionary medicine. In contrast to parenteral injection, noninvasive mucosal vaccination minimizes systemic inflammation. Moreover, pre-existing adenovirus immunity does not interfere appreciably with the potency of an adenovirus-vectored nasal vaccine. Nasal administration of adenovirus vectors encoding pathogen antigens is not only fear free and painless, but also confers rapid and sustained protection against mucosal pathogens as a drug-vaccine duo since adenovirus particles alone without transgene expression can induce an anti-influenza state in the airway. In addition to human vaccination, animals can also be mass immunized by this class of vectored vaccines. PMID- 22043956 TI - Developments in virus-like particle-based vaccines for infectious diseases and cancer. AB - Virus-like particles hold great promise for the development of effective and affordable vaccines. Indeed, virus-like particles are suitable for presentation and efficient delivery of linear as well as conformational antigens to antigen presenting cells. This will ultimately result in optimal B-cell activation and cross-presentation with both MHC class I and II molecules to prime CD4(+) T helper as well as CD8(+) cytotoxic T cells. This article provides an update on the development and use of virus-like particles as vaccine approaches for infectious diseases and cancer. PMID- 22043957 TI - Chlamydia vaccines: recent developments and the role of adjuvants in future formulations. AB - Bacteria of the genus Chlamydia cause a plethora of ocular, genital and respiratory diseases that continue to pose a considerable public health challenge worldwide. The major diseases are conjunctivitis and blinding trachoma, non gonococcal urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility and interstitial pneumonia. The rampart asymptomatic infections prevent timely and effective antibiotic treatments, and quite often clinical presentation of sequelae is the first evidence of an infection. Besides, significant broad coverage in population screening and treatment is economically and logistically impractical, and mass education for public awareness has been ineffective. The current medical opinion is that an efficacious prophylactic vaccine is the best approach to protect humans from chlamydial infections. Unfortunately, a human vaccine has yet to be realized despite successful veterinary vaccines. Fortunately, recent advances in chlamydial immunobiology, cell biology, molecular pathogenesis, genomics, antigen discovery and animal models of infections are hastening progress toward an efficacious vaccine. Thus, it is established that Chlamydia immunity is mediated by T cells and a complementary antibody response, and several potential vaccine candidates have been identified. However, further advances are needed in effective vaccine delivery systems and safe potent adjuvants to boost and sustain immune responses for long-lasting protective immunity. This article focuses on the current status of human chlamydial vaccine research, specifically how application of new delivery systems and human compatible adjuvants could lead to a timely achievement of efficacious Chlamydia vaccines. The ranking of the candidate vaccine antigens for human vaccine development will await the availability of results from studies in which the antigens are tested by comparable experimental standards, such as antigen-adjuvant combination, route of delivery and possible toxicity. PMID- 22043955 TI - Heat shock proteins and cancer vaccines: developments in the past decade and chaperoning in the decade to come. AB - Molecular chaperone-peptide complexes extracted from tumors (heat shock protein [HSP] vaccines) have been intensively studied in the preceding two decades, proving to be safe and effective in treating a number of malignant diseases. They offer personalized therapy and target a cross-section of antigens expressed in patients' tumors. Future advances may rely on understanding the molecular underpinnings of this approach to immunotherapy. One property common to HSP vaccines is the ability to stimulate antigen uptake by scavenger receptors on the antigen-presenting cell surface and trigger T-lymphocyte activation. HSPs can also induce signaling through Toll-Like receptors in a range of immune cells and this may mediate the effectiveness of vaccines. PMID- 22043958 TI - From brain passage to cell adaptation: the road of human rabies vaccine development. AB - A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. Such candidates should be pure, potent, safe, effective and economical to produce, with broad cross-reactivity against viral variants of public health and veterinary importance. The history of licensed human vaccines reviewed herein demonstrates clearly how the field has evolved to the current state of more passive development and postexposure management. Modern cell culture techniques provide adequate viral substrates for production of representative verified virus seeds. In contrast to outdated nervous tissue-based rabies vaccines, once a suitable substrate is identified, production of high titer virus results in a major qualitative and quantitative difference. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates for consideration to meet the need for seed viruses in the future. PMID- 22043959 TI - Vaccination of travelers: how far have we come and where are we going? AB - Vaccine recommendations are a prominent part of health preparations before international travel. We review progress made in the past decade regarding vaccines used primarily by persons traveling from high-income countries to low- and middle-income countries. The combined hepatitis A-B vaccine, the recently licensed Vero cell-derived Japanese encephalitis vaccine and conjugated quadrivalent meningococcal vaccines are discussed. This article provides updates on yellow fever vaccine-associated visceral and neurologic adverse events, indications for influenza vaccine in travelers, the rapid immunization schedule for tick-borne encephalitis vaccine, schedules for postexposure rabies prophylaxis, and new insights about oral cholera vaccines following the outbreak in Haiti. The future should bring vaccines for serogroup B Neiserria meningitidis, dengue and malaria, as well as an inactivated yellow fever vaccine. PMID- 22043960 TI - Glycoconjugate vaccines and immune interactions, and implications for vaccination schedules. AB - Conjugate vaccines using diphtheria toxoid variant (CRM(197)), diphtheria toxoid and tetanus toxoid (TT) as carrier protein may induce immune interactions (interference or impairment as measured by lower antibody levels, or enhancement [higher antibody levels]) when coadministered with other vaccines. Immune enhancement occurs when two TT conjugates are coadministered. CRM(197) conjugate vaccines induce immune bystander interference when given with diphtheria-tetanus acellular pertussis vaccines, which reduces responses to coadministered Haemophilus influenzae type b vaccine conjugated to TT. These bystander effects are greater as the amount of CRM(197) administered increases. When large amounts of either TT or CRM(197) are coadministered, dose-related carrier-induced epitopic suppression may occur, affecting immune responses to meningococcal or pneumococcal polysaccharides. These observations have implications for vaccine scheduling. The range of available alternative vaccines means that specific vaccine coadministrations can avoid or reduce CRM(197)-induced interference. Potential interactions arising from new CRM(197) or TT conjugates will need to be thoroughly examined. PMID- 22043962 TI - Comparative photodynamic evaluation of new phenothiazinium derivatives against Propionibacterium acnes. AB - The screening of recently patented derivatives of the standard phenothiazinium agents methylene blue and toluidine blue was carried out against Propionibacterium acnes, the main bacterium associated with acne vulgaris. Comparative tests were made using the topical agent benzoyl peroxide (BPO) and standard tetracyclines. Each of the photosensitizers employed, including the lead compounds, was photobactericidal at lower concentrations than BPO, and produced a much more rapid kill than the tetracyclines. In addition, the tetracyclic and pentacyclic phenothiazinium derivatives exhibited high light:dark kill ratios, suggesting that these examples might be particularly useful in practice. PMID- 22043963 TI - Light is beneficial for infant circadian entrainment: an actigraphic study. AB - AIM: This article is a report of an exploratory study of the relation between light exposure and circadian rest-activity patterns in infants. BACKGROUND: Ambient light is a major environmental stimulus for regulation of circadian rhythm of sleep and wake in adults, but few studies have been conducted to examine environmental light exposure in relation to rest-activity circadian rhythm parameters of infants. METHODS: An intensive within-subject design was used with a convenience sample of 22 infants (mean postnatal age 49.8 days) who wore a combined light and activity monitoring device for seven consecutive days at home. For each infant, light data (lux) were aggregated over the 7 days into categories of illumination and expressed in mean minutes/day. Circadian light and activity parameters, including mesor, amplitude, acrophase and R(2) cosinor fit, were determined using cosinor analysis. Associations between light exposure and circadian rest-activity rhythm parameters were examined using correlation and regression analyses. Data were collected between 2006 and 2007. RESULTS: Infants spent only one-eighth of their daytime hours in an environment with >100 lux light level. There was a relatively large statistically significant relation between the acrophase of light exposure and the acrophase of activity. Increased duration of daily exposure to >100 lux of illumination, and increased amplitude of circadian rhythm of light were associated with stronger circadian patterns of infant activity. CONCLUSION: Results suggest an association between light and activity patterns and that increasing duration of exposure to moderate light levels may be a simple and economical nursing intervention during the early postnatal weeks. PMID- 22043964 TI - Analysis of incurred crystal violet in Atlantic salmon (Salmo salar L.): comparison between the analysis of crystal violet as an individual parent and leucocrystal violet and as total crystal violet after oxidation with 2,3-dichloro 5,6-dicyanobenzoquinone. AB - Due to on-going concern about the occurrence of triphenylmethane dye residues in fish destined for human consumption, a depletion study of crystal violet in salmon was carried out. Atlantic salmon less than 12 months old were exposed to crystal violet in fresh water at 15 degrees C and subsequently sampled at 1, 7, 14, 28, 63 and 91 days after exposure. The salmon were then analysed by two analytical methods. In the first method, 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) was used to oxidise leucocrystal violet to its parent form. Total parent crystal violet was then analysed by LC-MS/MS. In the second method, crystal violet and leucocrystal violet were analysed individually by LC-MS/MS without oxidation. Both methods gave comparable results for total crystal violet concentrations, with a correlation of r(2)=0.69. Statistical treatment for 88 incurred salmon samples showed no significant difference between the two sets of results with t=1.68 and t(crit)=1.99. Up to 98% of crystal violet was metabolised to its leuco form in the salmon after 1 day of exposure and could be detected at significant concentrations (approximately 20 ug kg(-1)) 91 days after exposure. The depletion data also suggest that crystal violet has a half-life of approximately 15-16 days in salmon. PMID- 22043965 TI - Thermoresponsive copolymer containing a coumarin-spiropyran conjugate: reusable fluorescent sensor for cyanide anion detection in water. AB - A simple copolymer consisting of N-isopropylacrylamide and coumarin-conjugated spiropyran (CS) units, poly(NIPAM-co-CS), has been synthesized. This polymer enables selective fluorometric detection of cyanide anion (CN(-)) in water at room temperature. The polymer itself shows almost no fluorescence, but shows a strong blue fluorescence in the presence of CN(-) under irradiation of UV light. The fluorescence enhancement occurs via a nucleophilic interaction between CN(-) and the photoformed merocyanine form of the CS unit, leading to a localization of pi-electrons on the coumarin moiety. The polymer enables accurate determination of very low levels of CN(-) (>0.5 MUM). The polymer can be recovered from water by simple centrifugation at high temperature (>40 degrees C), due to the heat induced aggregation of the polymer. In addition, the polymer is regenerated by simple acid treatment, and the resulting polymer is successfully reused for further CN(-) sensing without loss of sensitivity. PMID- 22043966 TI - Ecological and evolutionary functional genomics--how can it contribute to the risk assessment of chemicals? PMID- 22043967 TI - miR-155 modulates microglia-mediated immune response by down-regulating SOCS-1 and promoting cytokine and nitric oxide production. AB - Innate immunity constitutes the first line of defence against both external and endogenous threats in the brain, and microglia cells are considered key mediators of this process. Recent studies have shown that microRNAs (miRNAs) may play a determinant role in the regulation of gene expression during innate immune responses. The major goal of this work was to investigate the contribution of a specific miRNA - miR-155 - to the modulation of the microglia-mediated immune response. For this purpose, in vitro studies were performed in N9 microglia cells to evaluate changes in the levels of this miRNA following microglia activation. A strong up-regulation of miR-155 expression was observed following microglia exposure to lipopolysaccharide, which was consistent with a decrease in the levels of the suppressor of cytokine signalling 1 (SOCS-1) protein, a key inhibitor of the inflammatory process and a predicted target of miR-155. The miR 155 knockdown by anti-miRNA oligonucleotides up-regulated SOCS-1 mRNA and protein levels and significantly decreased the production of nitric oxide and the expression of inflammatory cytokines and inducible nitric oxide synthase. Finally, treatment of neuronal primary cultures with conditioned medium obtained from microglia cells, in which miR-155 was inhibited before cell activation, decreased inflammatory-mediated neuronal cell death. Overall, our results show that miR-155 has a pro-inflammatory role in microglia and is necessary for the progression of the immune response through the modulation of SOCS-1, suggesting that, in a chronic inflammatory context, miR-155 inhibition can have a neuroprotective effect. PMID- 22043968 TI - ADHD drugs and serious cardiovascular events in children and young adults. AB - BACKGROUND: Adverse-event reports from North America have raised concern that the use of drugs for attention deficit-hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events. METHODS: We conducted a retrospective cohort study with automated data from four health plans (Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California, and OptumInsight Epidemiology), with 1,200,438 children and young adults between the ages of 2 and 24 years and 2,579,104 person-years of follow-up, including 373,667 person-years of current use of ADHD drugs. We identified serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) from health-plan data and vital records, with end points validated by medical-record review. We estimated the relative risk of end points among current users, as compared with nonusers, with hazard ratios from Cox regression models. RESULTS: Cohort members had 81 serious cardiovascular events (3.1 per 100,000 person-years). Current users of ADHD drugs were not at increased risk for serious cardiovascular events (adjusted hazard ratio, 0.75; 95% confidence interval [CI], 0.31 to 1.85). Risk was not increased for any of the individual end points, or for current users as compared with former users (adjusted hazard ratio, 0.70; 95% CI, 0.29 to 1.72). Alternative analyses addressing several study assumptions also showed no significant association between the use of an ADHD drug and the risk of a study end point. CONCLUSIONS: This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low. (Funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration.). PMID- 22043970 TI - A very late infection of an abdominal mesh following a pedicled TRAM flap harvest. AB - Pedicled transverse rectus abdominis myocutaneous (TRAM) flap is still a common procedure for breast reconstruction. To lessen the incidence of abdominal-wall abnormalities, the donor-site defect in the transverse rectus abdominis muscle is generally repaired with a prosthetic mesh. This carries the well-known risks of foreign-body implantation, the most serious of which is infection. We report here a case of a 46-year-old patient who presented with an infected mesh 6.5 years after pedicled transverse rectus abdominis myocutaneous (TRAM)-flap breast reconstruction, requiring subsequent removal of the mesh. This is the latest recorded presentation of an abdominal prosthetic mesh infection in the English literature. The onset of late mesh infection could be related to a transient systemic infection and bacteraemia. PMID- 22043969 TI - Short-term and long-term effects of orthopedic biodegradable implants. AB - Presently, orthopedic and oral/maxillofacial implants represent a combined $2.8 billion market, a figure expected to experience significant and continued growth. Although traditional permanent implants have been proved clinically efficacious, they are also associated with several drawbacks, including secondary revision and removal surgeries. Non-permanent, biodegradable implants offer a promising alternative for patients, as they provide temporary support and degrade at a rate matching tissue formation, and thus, eliminate the need for secondary surgeries. These implants have been in clinical use for nearly 25 years, competing directly with, or maybe even exceeding, the performance of permanent implants. The initial implantation of biodegradable materials, as with permanent materials, mounts an acute host inflammatory response. Over time, the implant degradation profile and possible degradation product toxicity mediate long-term biodegradable implant induced inflammation. However, unlike permanent implants, this inflammation is likely to cease once the material disappears. Implant-mediated inflammation is a critical determinant for implant success. Thus, for the development of a proactive biodegradable implant that has the ability to promote optimal bone regeneration and minimal detrimental inflammation, a thorough understanding of short- and long-term inflammatory events is required. Here, we discuss an array of biodegradable orthopedic implants, their associated short- and long- term inflammatory effects, and methods to mediate these inflammatory events. PMID- 22043971 TI - Vascular complications in orthopaedic surgery. AB - Vascular complications during orthopaedic surgery, although rare, do occur. Most vascular complications occur intraoperatively, immediately postoperatively or in the late postoperative period; they most commonly include lacerations, pseudoaneurysms, thrombosis, and arteriovenous fistulas. The operations most commonly associated with vascular injuries are knee arthroplasty, followed by hip arthroplasty, spinal surgery, and knee arthroscopy. Most commonly the popliteal artery is involved, followed by the tibial, superficial femoral, iliac, common and profunda femoral arteries. Color Doppler ultrasound is the initial imaging method used to evaluate a vascular injury. Computed tomography and magnetic resonance angiography are usually not applicable in joint replacement surgery because of the artifacts caused by the prostheses. When noninvasive imaging fails to reveal the injury, angiography is required. Traditional management of vascular surgical complications have included vascular surgical intervention. However, the availability of a vascular surgical team is required, and re-exploration of the operative site to treat acute ischemic complications of joint replacement may be difficult and may fail because the source of bleeding is not always apparent. In this setting, endovascular treatments such as balloon arterial thrombectomy, balloon angioplasty with and without stenting, and transcatheteral selective arterial embolization have been effective, successful, and safe interventional techniques in the acute or late postoperative period after elective orthopedic surgery. These techniques should be considered as the first option in the treatment of these lesions. PMID- 22043972 TI - Bioactive glass S53P4 and autograft bone in treatment of depressed tibial plateau fractures - a prospective randomized 11-year follow-up. AB - The clinical and radiological outcomes of bioactive glass (BAG)-S53P4 and autograft bone (AB) used as bone-graft substitutes in depressed tibial plateau fractures were evaluated in a prospective randomized 11-year follow-up study. All patients (n = 29) had sustained tibial plateau fractures with a joint-line depression of >3 mm. Fifteen patients (5 patients the BAG group, 10 patients in the AB group) participated in this long-term follow-up. X-rays were taken preoperatively, postoperatively, and at the long-term follow-up, and computed tomography (CT) scans were made at the long-term follow-up for evaluation of the bone substitute, osteoarthritis, the tibial-femoral angle, and deviation of mechanical axes. No material-dependent adverse effects were seen in any patient. The means of the articular surface depression on X-rays at the long-term follow up were 1.4 mm (range: 0-2 mm) in the BAG group and 1.4 mm (range: 0-4 mm) in the AB group, and on CT scans the means were 2.2 mm (range: 2-3 mm), and 2.1 mm (range: 0-3), respectively. No significant difference in the tibial-femoral angle or deviation of mechanical axes was observed between the two groups. BAG-S53P4 can be used as a bone substitute in depressed lateral tibial plateau fractures with good functional and radiological long-term results. PMID- 22043973 TI - Acute renal failure in orthopaedic surgery. AB - Orthopaedic diseases affect a broad spectrum of patients, and many of these have concomitant medical problems that may differ from those of the general surgical population. Acute postoperative renal failure is thought to arise secondary to acute tubular necrosis from volume depletion, reduction in glomerular filtration rate, hypotension, and nephrotoxic drugs. If acute renal failure occurs and necessitates hemodialysis, morbidity and mortality are significantly increased. To enhance the literature, we performed this study to review the rates and risk factors for acute renal failure in orthopaedic surgery. This information may be useful for orthopaedic surgeons and treating physicians during the rehabilitation stage, to provide a rationale to stratify a patient's risk of acute renal failure or death on the basis of perioperative medical factors and type of surgery, or for improved perioperative monitoring, better surveillance, and preventive measures to reduce this risk. PMID- 22043974 TI - Bone regeneration of tibial segmental defect using isotropic-pore structures hydroxyapatite/alumina bi-layered scaffold: in vivo pilot study. AB - Bone defects resulting from trauma or pathology represent a common and significant clinical problem. In this study, hydroxyapatite (HAp)-alumina bi layered scaffolds, which have the benefits of both HAp (i.e., osteointegration, osteoconduction) and alumina (i.e., hardness) were used as a bone substitute for the repair of large segmental defects (20 mm) created in a beagle tibia model. Highly porous bi-layered scaffolds with isotropic-pore structures were fabricated using a polymer-template coating technique. The pore sizes obtained using this approach ranged between 230 MUm and 470 MUm, and porosity was 91.61+/-1.28%. Using scanning electron microscopy and energy dispersive spectroscopy, it was confirmed that the frame of each bi-layered scaffold consisted of an alumina inner layer and HAp outer layer. The evaluation of bone regeneration within each scaffold after implantation in the beagle tibia was performed using CT, micro-CT, scintigraphy. New bone formation was evident in the large segmental defects treated with HAp/alumina scaffolds. It was concluded from this study that the HAp/alumina bi-layered scaffold is instrumental in inducing host-scaffold engraftment at the distal and proximal ends of the defect as well as distributing the newly formed bone throughout each scaffold 8 weeks post-implantation. PMID- 22043975 TI - Bioceramics in ossicular replacement prostheses: a review. AB - For many decades, bioceramic materials have been used in a variety of biomedical applications due to their biocompatibility, hardness, wear resistance and compressive strength properties. Bioceramic materials, including Bioglass, glass ceramic materials, and hydroxyapatite, have used to create total ossicular replacement prostheses and partial ossicular replacement prostheses. This review describes design factors associated with middle ear implants as well as clinical use of bioceramic materials in middle ear implants. PMID- 22043976 TI - Self-assembly of dimeric tetrathiafulvalene-calix[4]pyrrole: receptor for 1,3,5 trinitrobenzene. AB - The synthesis and binding properties of a tetrathiafulvalene (TTF) calix[4]pyrrole receptor 2 appended with one 3,5-dinitrobenzoate guest moiety are reported. The preliminary studies revealed that the receptor is self-complexing into a dimer receptor 2*2. The self-complexation of the receptor leads to preorganization--in its 1,3-alternate conformation--and as a result hereof, the dimer receptor 2*2 is displaying a 2 order higher binding affinity toward analytes (e.g., 1,3,5-trinitrobenzene) than the model tetrathiafulvalene (TTF) calix[4]pyrrole receptor 3. PMID- 22043977 TI - Attitudes towards abortion among trainees in obstetrics/gynecology and clinical genetics. AB - This study aimed to provide knowledge about attitudes towards abortion among Danish physicians in training in the specialties of obstetrics/gynecology and clinical genetics. The study was a questionnaire survey among trainees in these specialties. Ninety-six responded. Trainees in clinical genetics were more pro abortion than those in obstetrics/gynecology (p=0.04). Of the respondents, 30 versus 48% found working with early and late abortions unpleasant. Nearly half agreed that they had chosen their specialty despite having to counsel and treat women having abortions. Twenty-one percent agreed that working with late abortion affected their job satisfaction negatively. Those agreeing with the above statements had a tendency towards lower pro-abortion scores than those who were indifferent or who disagreed but the differences were not significant. A substantial fraction of physicians in training have negative feelings associated with abortion-related work and require support in handling and coping with these challenges. PMID- 22043978 TI - Early detection of drug use and bullying in secondary school children by using a three-dimensional simulation program. AB - The current study analyzes the psychometric properties of an innovative three dimensional (3D) simulation program, entitled Mii-School (MS), designed for the early detection of drug use and bullying in Secondary School children. This computer program showed adequate reliability and construct validity. The factorial structure, as well as the explanatory weight of the different factors, is presented. In addition, the results of a parallel version in paper and pencil format are also presented and compared with those of the computerized version (i.e., MS). There was a statistically significant difference between the two formats in the total (i.e., combined) sore of risk. When drug use and bullying were separately analyzed, differences were found only with regard to drug use. The relevance of these results as well as the suitability of this type of 3D instrument for the early detection of risky behaviors in young people are discussed. PMID- 22043979 TI - Humiliation or care? A qualitative study of patients' and health professionals' experiences with tuberculosis treatment in Norway. AB - AIM: Directly observed treatment (DOT) has been implemented globally as a strategy in treatment of tuberculosis. Studies from high-endemic settings show that DOT involves social and economical burdens for patients, but little is known about experiences with practicing DOT in low-endemic settings. The present study explores patients' and health professionals' views and experiences with DOT in Norway. METHOD: In-depth interviews were conducted with 22 patients originating from Somalia and Ethiopia and with 20 health professionals. Data from the interviews were analysed using systematic text condensation. FINDINGS: We found that there was little room for patients to negotiate whether or not to consent to the organization of treatment (DOT). Patients told that it was difficult to question the way treatment was organized, as they got the impression that there was no other way of gaining access to medication. Both patients and health professionals reported that persuasion based on authority and subtle threats was used as means to facilitate patients' acceptance of DOT. A majority of patients experienced DOT as humiliating and discriminating, while some had the experience of being cared for. Patients who attended school or had occupational obligations reported high social costs related to the treatment. Patients with positive experiences told that they had been given an opportunity to negotiate flexible treatment schedules and emphasized the importance of continuity among health professionals. Health professionals had divergent views and practices. Some argued that patients should be treated equally, while others argued for an individualized and flexible approach. CONCLUSION: The practice of DOT reflects societal power structures that influence the clinical interactions between health professionals and patients. To avoid experiences of disempowerment and humiliation among patients, treatment and care should be organized in a way that safeguards patients' right to consent to treatment and that allows patients to negotiate an individualized treatment schedule. PMID- 22043981 TI - Induction of contact-dependent CD8(+) regulatory T cells through stimulation with staphylococcal and streptococcal superantigens. AB - The bacterial superantigen exotoxins of Staphylococcus aureus and Streptococcus pyogenes are potent stimulators of polyclonal T-cell proliferation. They are the causes of toxic shock syndrome but also induce CD25(+) FOXP3(+) regulatory cells in the CD4 compartment. Several studies have recently described different forms of antigen-induced regulatory CD8(+) T cells in the context of inflammatory diseases and chronic viral infections. In this paper we show that bacterial superantigens are potent inducers of human regulatory CD8(+) T cells. We used four prototypic superantigens of S. aureus (toxic shock syndrome toxin-1 and staphylococcal enterotoxin A) and Str. pyogenes (streptococcal pyrogenic exotoxins A and K/L). At concentrations below 1 ng/ml each toxin triggers concentration-dependent T-cell receptor Vbeta-specific expression of CD25 and FOXP3 on CD8(+) T cells. This effect is independent of CD4(+) T-cell help but requires antigen-presenting cells for maximum effect. The cells also express the activation/regulatory markers cytotoxic T-lymphocyte antigen-4 and glucocorticoid induced tumour necrosis factor receptor-related protein and skin homing adhesins CD103 and cutaneous lymphocyte-associated antigen. Superantigen-induced CD25(+) FOXP3(+) CD8(+) T cells were as potent as freshly prepared naturally occurring CD4(+) regulatory T cells in suppressing proliferation of CD4(+) CD25(-) T cells in response to anti-CD3 stimulation. Although superantigen-induced CD8(+) CD25(+) FOXP3(+) express interleukin-10 and interferon-gamma their suppressive function is cell contact dependent. Our findings indicate that regulatory CD8(+) T cells may be a feature of acute bacterial infections contributing to immune evasion by the microbe and disease pathogenesis. The presence and magnitude of regulatory CD8(+) T-cell responses may represent a novel biomarker in such infections. Superantigen-induced regulatory CD8(+) T cells also have therapeutic potential. PMID- 22043982 TI - A novel homosesquiterpenoid from the stems of Cinnamomum burmanii. AB - A novel homosesquiterpenoid, burmanol (1), along with 16 known compounds, including one triterpenoid, one quinol, two chlorophylls, two coumarins, two steroids, three lignans and five benzenoids were obtained from the stems of Cinnamomum burmanii (Lauraceae). The structures of these compounds were determined on the basis of spectroscopic analysis. PMID- 22043983 TI - Serological monitoring of protection of sheep against Echinococcus granulosus induced by the EG95 vaccine. AB - Although immunity to Echinococcus granulosus in sheep has been shown to be antibody-mediated and complement-dependent and can be passively transferred in colostrum, in animals vaccinated with EG95, the relationship between protection against an oral challenge infection with E. granulosus eggs and anti-EG95 IgG ELISA absorbance values at the time of challenge has not been satisfactorily proven. Using a combination of results from three EG95 vaccination trials, we have found that the IgG ELISA absorbance at the time of challenge infection explains approximately 50% (P <= 0.001) of the variability in the percentage protection against an oral challenge with E. granulosus eggs (transformed with arcsin). PMID- 22043984 TI - Nanoparticle shape anisotropy dictates the collective behavior of surface-bound ligands. AB - We report on the modification of the properties of surface-confined ligands in nanoparticle systems through the introduction of shape anisotropy. Specifically, triangular gold nanoprisms, densely functionalized with oligonucleotide ligands, hybridize to complementary particles with an affinity that is several million times higher than that of spherical nanoparticle conjugates functionalized with the same amount of DNA. In addition, they exhibit association rates that are 2 orders of magnitude greater than those of their spherical counterparts. This phenomenon stems from the ability of the flat, extended facets of nonspherical nanoparticles to (1) support more numerous ligand interactions through greater surface contact with complementary particles, (2) increase the effective local concentration of terminal DNA nucleotides that mediate hybridization, and (3) relieve the conformational stresses imposed on nanoparticle-bound ligands participating in interactions between curved surfaces. Finally, these same trends are observed for the pH-mediated association of nanoparticles functionalized with carboxylate ligands, demonstrating the generality of these findings. PMID- 22043985 TI - Advances in quantitative phosphoproteomics. PMID- 22043986 TI - Does physical activity reduce risk for Alzheimer's disease through interaction with the stress neuroendocrine system? AB - Lack of physical activity (PA) is a risk factor for Alzheimer's disease (AD), and PA interventions are believed to provide an effective non-pharmacological approach for attenuating the symptoms of this disease. However, the mechanism of action of these positive effects is currently unknown. It is possible that the benefits may be at least partially mediated by the effects on the neuroendocrine stress system. Chronic stress can lead to dysfunction of the hypothalamic pituitary-adrenal (HPA) axis, leading to aberrant basal and circadian patterns of cortisol secretion and a cascade of negative downstream events. These factors have been linked not only to reduced cognitive function but also increased levels of amyloid-beta plaques and protein tau "tangles" (the neuropathological hallmarks of AD) in the non-demented mouse models of this disease. However, there is evidence that PA can have restorative effects on the stress neuroendocrine system and related risk factors relevant to AD. We explore the possibility that PA can positively impact upon AD by restoring normative HPA axis function, with consequent downstream effects upon underlying neuropathology and associated cognitive function. We conclude with suggestions for future research to test this hypothesis in patients with AD. PMID- 22043987 TI - Ecological-level associations between highly processed food intakes and plasma phospholipid elaidic acid concentrations: results from a cross-sectional study within the European prospective investigation into cancer and nutrition (EPIC). AB - Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations. PMID- 22043989 TI - Growth inhibition of human non-small lung cancer cells h460 by green tea and ginger polyphenols. AB - Non small cell lung cancer is known to resist apoptotic stimuli of various antitumor agents and become progressively incurable. The present study was undertaken to evaluate the in vitro antineoplastic effect of polyphenols extracted from both green tea (GTPs) and ginger (GPs) on non-small cell lung cancer cells (NSCLC-NCI-H460). METHODS: The direct antitumor effect of GTPs and GPs on H460 cells was assessed by investigating the proliferation rate, metabolic activity assay (MTT method) and the apoptotic effect (determined by an annexin V apoptosis assay). Also, the inhibition concentrations (IC50) of both extracts and the levels of P 53 and Bcl-2 proteins were determined. RESULTS: GTPs and GPs have inhibited the proliferation of H460 cells in a dose-dependent manner. At the end of treatment period (96 h) the cell population has decreased to 16% and 26% when treated with 80MUg GTPs or GPs, respectively, compared to the untreated cells. The IC50 values of both extracts were 32.9 and 55.5 g/ml, respectively. GTPs was more effective in reduction of cell metabolic activity (measured by MTT assay), where cell count decreased to 22% compared to 64% in cells treated with similar concentration (80MUg) of GPs. Lower concentration (20MUg) of cisplatin induced 15% reduction in cell metabolic activity. Moreover, 80MUg of GTPs and GPs extracts induced apoptosis by 71% and 39% of the living cells, respectively. The apoptotic effect of both extracts, especially GTPs, seems to be mediated by both P 53 and Bcl-2. CONCLUSION: The study reports the antiproliferative and apoptosis mediated cytotoxic effects of green tea and ginger polyphenolic extracts on human H460 cell line, indicating their promising chemopreventive effect against lung cancer. PMID- 22043990 TI - Current and emerging strategies in bladder cancer. AB - Urothelial cell carcinoma is one of the most common malignancies of the urinary tract. The standard of care, intravesical chemo- and immunotherapy, while effective, is associated with a considerable side-effect profile and approximately 30% of patients either fail to respond to treatment or suffer recurrent disease within 5 years. In the setting of muscle-invasive urothelial carcinoma, use of neoadjuvant chemotherapy is associated with overall survival benefit. Muscle invasive bladder cancer is life threatening, showing modest chemosensitivity, and usually requires radical cystectomy. Although bladder cancer is fairly well-genetically characterized, clinical trials with molecularly targeted agents have, in comparison to other solid tumors, been few in number and largely unsuccessful. Hence, bladder cancer represents a considerable opportunity and challenge for alternative therapies. In this review, we will focus on promising global or pathway-based approaches (epigenetic modulators, kinase inhibitors, angiogenesis blockage, peroxisome proliferator-activated receptor gamma agonists, apoptosis inductors, virus therapy) supported by a deeper understanding of molecular biology of urothelial carcinoma, which have been recently tested in clinical trials. PMID- 22043991 TI - Recent developments of small molecule EGFR inhibitors based on the quinazoline core scaffolds. AB - Progress in identifying and understanding the molecular and cellular causes of cancer has led to the discovery of anomalies that characterize cancer cells and that represent targets for the development of cancer therapeutics. One such target is the epidermal growth factor receptor (EGFR), a transmembrane protein that is frequently dysregulated in cancer cells and associated with the development, progression and aggressiveness of a number of malignancies. Inhibition of EGFR signaling has thus been identified as an attractive strategy in control of tumor proliferation, and over a decade of intense activity in the field has culminated in the discoveries and subsequent approvals of gefitinib and erlotinib for the treatment of non-small cell lung cancer. However, the drug's resistance to gefitinib and erlotinib has been clinically observed. Therefore, intensive efforts have been made in the discovery of novel potent and selective EGFR inhibitors. This review will focus on the developments of small molecule EGFR inhibitors based on the quinazoline core scaffolds in recent 5 years. Diverse EGFR inhibitors are classified as 4-anilinoquinazolines and 4 nonanilininoquinazolines, their biological data are described, and the structure activity relationships (SARs) are discussed. PMID- 22043992 TI - New targeted therapies for anaplastic thyroid cancer. AB - Anaplastic thyroid cancer (ATC) is often incurable because it doesn't respond to radioiodine, radiotherapy or chemotherapy, and new therapeutic approaches are needed. Peroxisome proliferator-activated receptor-gamma (PPARg) gene and protein are present in ATC cells, and PPARg ligands inhibit cell proliferation, induce apoptosis, and also down regulate the invasive potential of ATC cells. Also, inhibitors of the Aurora serine/threonine kinases have antineoplastic effect on ATC cells in vitro and on ATC xenografts. Tyrosine kinases inhibitors are actually under evaluation for the treatment of ATC, for example imanitib or sorafenib. Other studies have focused on evaluating antiangiogenic agents for treatment of ATC. These agents include: combretastatin A4 phosphate, aplidin, PTK787/ZK222584, and human VEGF monoclonal antibodies (bevacizumab, cetuximab). Small-molecule adenosine triphosphate (ATP) competitive inhibitors directed intracellularly at epidermal growth factor receptor (EGFR)'s tyrosine kinase, such as erlotinib, or gefitinib are also under evaluation. The development of drugs that have multiple therapeutic targets and the utilization of multiple cancer-targeting agents are both emerging strategies for ATC treatment. For example, a preclinical study evaluated the activity of a dual inhibitor of EGFR and vascular endothelial growth factor (VEGF), NVP-AEE788, alone and in combination with paclitaxel for the treatment of ATC. Even if new therapeutic approaches against ATC are under development, more research is needed to finally identify therapies able to control and to cure this disease. The possibility of testing the sensitivity of primary ATC cells from each subject to different drugs could increase the effectiveness of the treatment in the next future. PMID- 22043993 TI - Downregulation of hypoxia-related responses by novel antitumor histone deacetylase inhibitors in MDAMB231 breast cancer cells. AB - The tumor microenvironment is characterized by a poor circulation which results in the selection of neoplastic cells that can grow or survive under hypoxic conditions. The relationship between hypoxia and histone deacetylase (HDAC) inhibitors has been previously established. In this work we evaluated the effects of novel HDAC inhibitors (the natural peptide FR235222 and three tetrapeptide analogs) in the human breast cancer cell line MDAMB231, cultured under hypoxia (2% O2 ? 14 mmHg) or normoxia (20% O2 ? 140 mmHg). First, we found that the novel HDAC inhibitors reduced cell proliferation in MDAMB231 cells at an extent which was similar or even higher than that exerted by the classic HDAC inhibitors trichostatin-A and suberoylanilide hydroxamic acid. More interestingly, the antiproliferative effects of the novel HDAC inhibitors were, in general, significantly higher in hypoxic cells than in normoxic controls. Hypoxic MDAMB231 cells expressed high levels of the hypoxia-inducible factor (HIF)-1alpha and HIF 1alpha-related genes, such as vascular endothelial growth factor, Bcl-2/E1B 19 kDa interacting protein-3, glucose transporter-1, carbonic anhydrase IX, as determined by Western blot analysis and qRT-PCR. Finally, we found that HIF 1alpha and HIF-1alpha-related genes were significantly downregulated by FR235222 and analogs. In conclusion, the identification of novel effects exerted by the HDAC inhibitors, characterized by a strong efficacy in inhibiting the expression of HIF-1alpha and its related genes, may have important implications in the pharmacological control of several tumors, including breast cancer, characterized by the presence of hypoxia, angiogenesis and metabolic derangements. PMID- 22043995 TI - Chemoinformatics in multi-target drug discovery for anti-cancer therapy: in silico design of potent and versatile anti-brain tumor agents. AB - A brain tumor (BT) constitutes a neoplasm located in the brain or the central spinal canal. The number of new diagnosed cases with BT increases with the pass of the time. Understanding the biology of BT is essential for the development of novel therapeutic strategies, in order to prevent or deal with this disease. An active area for the search of new anti-BT therapies is the use of Chemoinformatics and/or Bioinformatics toward the design of new and potent anti BT agents. The principal limitation of all these approaches is that they consider small series of structurally related compounds and/or the studies are realized for only one target like protein. The present work is an effort to overcome this problem. We introduce here the first Chemoinformatics multi-target approach for the in silico design and prediction of anti-BT agents against several cell lines. Here, a fragment-based QSAR model was developed. The model correctly classified 89.63% and 90.93% of active and inactive compounds respectively, in training series. The validation of the model was carried out by using prediction series which showed 88.00% of correct classification for active and 88.59% for inactive compounds. Some fragments were extracted from the molecules and their contributions to anti-BT activity were calculated. Several fragments were identified as potential substructural features responsible of anti-BT activity and new molecular entities designed from fragments with positive contributions were suggested as possible anti-BT agents. PMID- 22043994 TI - Are KRAS/BRAF mutations potent prognostic and/or predictive biomarkers in colorectal cancers? AB - KRAS and BRAF mutations lead to the constitutive activation of EGFR signaling through the oncogenic Ras/Raf/Mek/Erk pathway. Currently, KRAS is the only potential biomarker for predicting the efficacy of anti-EGFR monoclonal antibodies (mAb) in colorectal cancer (CRC). However, a recent report suggested that the use of cetuximab was associated with survival benefit among patients with p.G13D-mutated tumors. Furthermore, although the presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC, it remains unknown whether patients with BRAF-mutated tumors experience a survival benefit from treatment with anti-EGFR mAb. Thus, the prognostic or predictive relevance of the KRAS and BRAF genotype in CRC remains controversial despite several investigations. Routine KRAS/BRAF screening of pathological specimens is required to promote the appropriate clinical use of anti-EGFR mAb and to determine malignant phenotypes in CRC. The significance of KRAS/BRAF mutations as predictive or prognostic biomarkers should be taken into consideration when selecting a KRAS/BRAF screening assay. This article will review the spectrum of KRAS/BRAF genotype and the impact of KRAS/BRAF mutations on the clinicopathological features and prognosis of patients with CRC, particularly when differentiating between the mutations at KRAS codons 12 and 13. Furthermore, the predictive role of KRAS/BRAF mutations in treatments with anti-EGFR mAb will be verified, focusing on KRAS p.G13D and BRAF mutations. PMID- 22043996 TI - Genistein and its synthetic analogs as anticancer agents. AB - Genistein, one of the predominant isoflavones derived from soybeans, has been shown beneficial effects in cancer prevention and treatment. There is an accumulating body of experimental evidences suggesting that genistein affects cancer progression by increasing apoptosis, inducing cell cycle arrest,modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. During last decade, many researchers have conducted extensive studies by synthesizing amounts of structurally-modified derivatives based on the isoflavone skeleton of genistein to enhance its anticancer activity, some analogs of which possess more potent activities of the prevention and/or treatment of various cancers. In this review, we summarized the current knowledge regarding anticancer effects,structure-activity relationships and action mechanisms of genistein and its synthesized analogs, which would be beneficial to the rational design of new genistein derivatives as anticancer drugs. PMID- 22043997 TI - Pharmacologic inhibition of mTOR improves lapatinib sensitivity in HER2 overexpressing breast cancer cells with primary trastuzumab resistance. AB - Lapatinib, a dual EGFR/HER2 kinase inhibitor, is approved for use in patients with trastuzumab-refractory HER2- overexpressing breast cancer. Increased PI3K signaling has been associated with resistance to trastuzumab, although its role in lapatinib resistance remains unclear. The purpose of the current study was to determine if PI3K/mTOR activity affects lapatinib sensitivity. Reduced sensitivity to lapatinib was associated with an inability of lapatinib to inhibit Akt and p70S6K phosphorylation. Transfection of constitutively active Akt reduced lapatinib sensitivity, while kinase-dead Akt increased sensitivity. Knockdown of 4EBP1 also increased lapatinib sensitivity, in contrast to p70S6K knockdown, which did not affect response to lapatinib. Pharmacologic inhibition of mTOR using rapamycin or ridaforolimus increased lapatinib sensitivity and reduced phospho-Akt levels in cells that showed poor response to single-agent lapatinib, including those transfected with hyperactive Akt. Finally, combination mTOR inhibition plus lapatinib resulted in synergistic inhibition of proliferation, reduced anchorage-independent growth, and reduced in vivo tumor growth of HER2- overexpressing breast cancer cells that have primary trastuzumab resistance. Our data suggest that PI3K/mTOR inhibition is critical for achieving optimal response to lapatinib. Collectively, these experiments support evaluation of lapatinib in combination with pharmacologic mTOR inhibition as a potential strategy for inhibiting growth of HER2-overexpressing breast cancers that show resistance to trastuzumab and poor response to lapatinib. PMID- 22043998 TI - Cranberry as promising natural source of potential anticancer agents: current evidence and future perspectives. AB - BACKGROUND: Accumulating evidence suggest that dietary modification can lower the risk for several cancer types' development. Cranberry in particular, has been shown to have anti-oxidative, -inflammatory and -proliferative properties in vitro. OBJECTIVE: To present the latest knowledge regarding the role of cranberry extracts against human cancer several types. METHODS: A review of the literature documenting both in vitro and in vivo anti-cancer effects of whole cranberry and/or its extracts is conducted. CONCLUSIONS: Current data provide evidence for several anti-cancer properties of either whole cranberry and/or its extracts. The discovery of the specific cranberry components and the appropriate concentrations that exert such beneficial effects along with verification of the preliminary in vitro results in in vivo settings could potentially lead to the invention of novel safer and efficient anti-cancer therapeutic agents. PMID- 22043999 TI - Hepatocarcinogenesis and ceramide/cholesterol metabolism. AB - Sphingolipids (SLs) and cholesterol are critical structural components of membrane bilayers. Although recent evidence has revealed an emerging role of both lipids in signaling pathways, their contribution to cancer development and treatment has been largely overlooked. Sphingolipids comprise a family of bioactive lipids with divergent roles in numerous cellular processes. In particular, ceramide is the prototype of SLs and identified as a cell death effector whose levels increase in response to apoptotic stimuli such as ionizing radiation or chemotherapy. In the liver, ceramide/cholesterol accumulation contributes to a wide range of pathologies, including the transition from steatosis to steatohepatitis, which can further progress to cirrhosis and hepatocellular carcinoma (HCC). Moreover, different studies have shown that either pharmacologic ceramide accumulation or systemic intravenous administration of liposomal ceramide is an effective approach against HCC. In addition, mitochondrial cholesterol trafficking has emerged as a novel factor regulating cell death pathways and HCC tumor growth and chemoresistance. Due to the poor efficacy of current HCC treatments, understanding the role of ceramide/cholesterol in HCC may open up novel avenues for therapy. Here we describe recent evidence indicating that ceramide-generating agents and/or pharmacological targeting of sphingolipid/cholesterol metabolism, alone or in combination with other chemotherapeutic compounds, may be a promising strategy in HCC management. PMID- 22044000 TI - The sequence specificity of the anti-tumour drug, cisplatin, in telomeric DNA sequences compared with consecutive guanine DNA sequences. AB - The sequence specificity of the anti-tumour drug, cisplatin, was determined in a DNA sequence that contained seven telomeric repeats and a run of ten consecutive guanine bases. Cisplatin preferentially forms DNA adducts at consecutive guanine sequences. Hence these DNA sequences were examined in order to gain an insight into the important human genomic regions that are damaged by cisplatin. A polymerase stop/linear amplification assay was employed with an automated DNA capillary sequencer and laser-induced fluorescence detection to quantitatively determine the DNA sequence specificity of cisplatin in a plasmid clone containing seven telomeric repeats and a sequence of ten consecutive guanine bases. It was found that cisplatin preferentially damaged the ten consecutive guanine sequence although the telomeric DNA sequences were also a major site of cisplatin adduct formation. PMID- 22044001 TI - Molecular probing and imaging of histone deacetylase inhibitors in cancer treatment. AB - Molecules that inhibit histone deacetylases (HDACs) activity have shown a great promise as anticancer agents since they interfere with cell proliferation and angiogenesis, induce cell differentiation and promote apoptosis. A number of HDACIs (for example: SAHA) have been approved by FDA for the treatment of cancer in different stages of clinical trials. HDAC inhibition proves to be a worthy strategy for cancer therapy. Thus, the distribution and metabolism of HDACIs in vivo are of significant clinical value for diagnosis and assessment of therapeutic efficacy. Molecular imaging is one of the primary tools used to noninvasively evaluate biological processes at the cellular and molecular level in living subjects. Various imaging modalities, including optical bioluminescence/ fluorescence, PET, SPECT, MRI, CT and US are all successfully used to assess the anatomic or functional dissemination of tissues and specific molecular targets, such as imaging molecular interactions, tumor vitality, apoptosis, angiogenesis and response to cancer treatment in the body. The utility of molecular imaging for monitoring HDACIs provides a perfect strategy for deeper understanding about cancer. In this article, the recent progresses of molecular imaging for assessing HDACIs are reviewed. In addition, how imaging can be used, at least experimentally, to assess specific molecular targets is also discussed. PMID- 22044002 TI - The stem cell niche as a pharmaceutical target for prevention of skeletal metastases. AB - Advanced cancers of the prostate and breast commonly progress by metastasizing to the skeleton, where they are incurable but cause serious morbidity and contribute to mortality. Growth of tumor in bone takes several years, opening a large window for pharmaceutical prevention of metastatic progression. Bone provides a unique microenvironment for tumor growth, including niches occupied by hematopoietic and mesenchymal stem cells. Recent data suggest that circulating tumor cells usurp these niches and compete with the normal stem cell occupants. Agents that encourage normal hematopoiesis or bone formation could inhibit colonization of bone by tumor stem cells and prevent or delay metastatic progression. It may be possible to develop high-throughput assays to test compounds for their ability to suppress tumor stem cell occupation of skeletal niches, thus decreasing metastatic progression in at-risk patients. PMID- 22044003 TI - Synthesis of Cis-fused pyran indolocarbazole derivatives that inhibit FLT3 kinase and the DNA damage kinase, checkpoint kinase 1. AB - Protein kinases are important enzymes in solid tumour and leukaemia pathologies. Their structures are well understood at the atomic level and their key role in the progression of certain cancers makes them valuable targets for anti-cancer therapy. Through medicinal chemical approaches, we developed an efficient preparative stereospecific synthesis of N12, N13 pyran-bridged indolocarbazoles that opens access to functional diversity within this previously challenging series. We focused upon the indolocarbazole class of chemical inhibitors, which includes S27888, an inhibitor we previously identified. We used biochemical and cell-based assays to identify small molecule inhibitors of Checkpoint kinase 1 (Chk1), a serine/threonine protein kinase that is activated when cancer cells are treated with genotoxic agents. These compounds show a promising inhibitory profile on Chk1. Furthermore, these compounds are active against FLT3, which is a tyrosine kinase that is frequently activated in human leukaemias. These data suggest that this chemical class may provide a source of therapeutic compounds for a broad range of human cancers. PMID- 22044004 TI - Melanoma and epigenetic treatment: past and future. AB - Melanoma is the most aggressive form of skin cancer and advanced stages are inevitably resistant to conventional therapeutic agents. In particular, epigenetic strategies might open interesting new perspectives in combination with conventional ones. Current therapeutic strategies, in particular for metastatic melanoma, do not give great results in terms of survival. Herein, I review HDACis and microRNAs for melanoma. A critical discussion of all the recent findings on this topic is also included. In my view, further studies are needed to understand the toxicity of these treatments in order to improve survival of melanoma patients. PMID- 22044005 TI - Curcumin and its formulations: potential anti-cancer agents. AB - Curcumin, one of the most studied chemopreventive agents, is a natural compound extracted from Curcuma longa L. Extensive research over the last half century has revealed that curcumin can inhibit the proliferation of various tumor cells in culture, prevent carcinogen induced cancers in rodents and inhibit the growth of human tumors in xenotransplant or orthotransplant animal models. Several phase I and phase II clinical trials indicated that curcumin is quite safe and may exhibit therapeutic efficacy. The utility of curcumin is limited by its lack of water solubility and relatively low in vivo bioavailability. Multiple approaches including nanoparticles, liposomes, micelles and phospholipid complexes are being sought to overcome these limitations. This review describes the general properties of curcumin and its potential effect against cancer including evidences of its antitumor action in vitro, in vivo, clinically and the strategies to overcome its low bioavailability. PMID- 22044006 TI - Tubulin-based structure-affinity relationships for antimitotic Vinca alkaloids. AB - The Vinca alkaloids are a group of widely used anticancer drugs, originally extracted from the Madagascar periwinkle, that disrupt microtubule dynamics in mammalian cells by interfering with proper assembly of alpha,beta-tubulin heterodimers. They favor curved tubulin assemblies that destabilize microtubules and induce formation of spiral aggregates. Their binding energy profiles have been characterized by means of sedimentation velocity assays and the binding site of vinblastine at the interface between two tubulin dimers (alpha1beta1 ? alpha2beta2) has been ascertained by X-ray crystallographic studies on a complex of tubulin with the stathmin-like domain of protein RB3, albeit at relatively low resolution. Here we use molecular modeling and simulation techniques to build, refine and perform a comparative analysis of the three-dimensional complexes of vinblastine, vincristine, vinorelbine and vinflunine with a beta1alpha2-tubulin interface in explicit water to rationalize the binding affinity differences in structural and energetic terms. Our results shed some more light into the binding determinants and the structure-activity relationships of these clinically useful agents. PMID- 22044007 TI - Combination antiretroviral therapy with protease inhibitors in HIV-infected pregnancy. AB - OBJECTIVE: To evaluate the possible association between protease inhibitor (PI) and premature birth and low birth-weight in HIV-infected pregnancies. MATERIALS AND METHODS: Data were collected retrospectively for maternal and pregnancy characteristics, antiretroviral medication, lowest CD4 count and highest viral load during pregnancy, and pregnancy outcomes. chi(2) Analysis, Student's t-test, and multiple logistic regression analysis were performed. RESULTS: Data from 161 HIV-infected women who delivered singleton gestation were analyzed. Fifty-three received an antepartum regimen with PI, 84 received a regimen without PI, and six did not receive antepartum treatment. The mean estimated gestational age (EGA)+/- SD at delivery was 37.7 +/- 3.2 weeks. The premature birth rate was 18.4%. No difference was detected between women receiving the antiretroviral regimen including PI and those on the regimen without PI or on no antepartum medication with regard to: EGA +/- SD at delivery (37.7 +/- 3.2 vs. 37.6 +/- 3.1 weeks, respectively, P=0.87), rate of premature birth (14% vs. 20.6%, respectively, P=0.32) and low birth-weight (12.5% vs. 20.2%, respectively, P=0.25). In multiple logistic regression analysis, PI was not associated with premature birth or low birth-weight. CONCLUSION: Women receiving antiretroviral therapy with PI have a similar rate of premature birth and low birth-weight as women receiving antiretroviral therapy without PI or on no medication. PMID- 22044009 TI - Resolution of activated background information in text comprehension. AB - The present experiments explored the resolution of activated background information in text comprehension. In Experiment 1, participants read passages that contained an elaboration section that was either consistent or qualified (inconsistent but then corrected to be consistent) with respect to the subsequently presented target sentence (see O'Brien et al., 1998). However, the experiment used two target sentences, and several filler sentences were inserted between the first and second target sentence. The results showed that the reading times for the first target sentence in the qualified elaboration version were significantly longer than those in the consistent elaboration version. These were consistent with O'Brien's study, and further indicated that the basic process captured by the memory-based view appears to generalize to the Chinese reader better than does the here-and-now view. More importantly, the results showed that the reading times for the second target sentence in the qualified elaboration version were as long as those in the consistent elaboration version. These further indicated that the activation of background information not only maintained the coherence of the text, but also allowed for the relevant information to be updated, resulting in a unified information set. When the information was reactivated during ongoing reading, it would be in the form of unified information. In Experiment 2, the first target sentence in each passage from Experiment 1 was converted to a filler sentence, and the second target sentence became the target sentence. The results of Experiment 2 showed that the reading times for the target sentence in the qualified elaboration version were significantly longer than those for the consistent elaboration version. These indicated that the delay between the target sentences and the elaboration section was not responsible for the lack of differences in Experiment 1, and confirmed the conclusion of Experiment 1. PMID- 22044008 TI - Prepregnancy body mass index, socioeconomic status, race/ethnicity and breastfeeding practices. AB - OBJECTIVE: While socioeconomic status (SES) and race/ethnicity are known predictors of breastfeeding practices, the added disparity caused by the rising rates of obesity among women of childbearing age remains untested. The purpose of this study was to examine differences in breastfeeding initiation and duration among black, white and Hispanic women of low and middle SES within the context of prepregnancy body mass index (BMI). METHODS: Data from the Early Childhood Longitudinal Study-Birth Cohort were analyzed. Adjusted logistic regression models were built to examine differences in breastfeeding initiation and duration for the three racial/ethnic groups of low and middle SES. RESULTS: Normal BMI Hispanic women of low SES demonstrated higher rates of breastfeeding initiation (74%) compared to other groups. Overweight/obese black women of low SES had lower rates of breastfeeding initiation. Overweight/obese Hispanic women of middle SES were significantly less likely to continue breastfeeding up to 4 months (OR: 0.65, 95% CI: 0.41, 0.98) compared to their white counterparts. Among women who initiated breastfeeding, overweight/obese white women of low SES had the highest rate of stopping within two months of giving birth (66.7%). CONCLUSIONS: Examination of SES and racial/ethnic differences within the context of prepregnancy weight revealed specific groups with low rates of breastfeeding initiation and duration. Interventions tailored for these at-risk groups are needed to increase the overall proportion of mothers and infants who benefit from the positive health outcomes associated with breastfeeding. PMID- 22044010 TI - Exploring the motivation jungle: predicting performance on a novel task by investigating constructs from different motivation perspectives in tandem. AB - Different theoretical viewpoints on motivation make it hard to decide which model has the best potential to provide valid predictions on classroom performance. This study was designed to explore motivation constructs derived from different motivation perspectives that predict performance on a novel task best. Motivation constructs from self-determination theory, self-regulation theory, and achievement goal theory were investigated in tandem. Performance was measured by systematicity (i.e. how systematically students worked on a problem-solving task) and test score (i.e. score on a multiple-choice test). Hierarchical regression analyses on data from 259 secondary school students showed a quadratic relation between a performance avoidance orientation and both performance outcomes, indicating that extreme high and low performance avoidance resulted in the lowest performance. Furthermore, two three-way interaction effects were found. Intrinsic motivation seemed to play a key role in test score and systematicity performance, provided that effort regulation and metacognitive skills were both high. Results indicate that intrinsic motivation in itself is not enough to attain a good performance. Instead, a moderate score on performance avoidance, together with the ability to remain motivated and effectively regulate and control task behavior, is needed to attain a good performance. High time management skills also contributed to higher test score and systematicity performance and a low performance approach orientation contributed to higher systematicity performance. We concluded that self-regulatory skills should be trained in order to have intrinsically motivated students perform well on novel tasks in the classroom. PMID- 22044011 TI - Translating intentions into nutrition behaviors via planning requires self efficacy: evidence from Thailand and Germany. AB - A first step towards the improvement of daily dietary behaviors is forming an intention to change one's nutrition. However, an intention by itself is not sufficient for successful action. Rather, to translate intentions into behavior, careful planning is recommended. Thus, planning constitutes a mediator between the intention and the behavior. However, if a person lacks self-efficacy, this mediation might fail. Previous research in Costa Rica and South Korea has identified perceived self-efficacy as a moderator of the intention-planning behavior relationship. To examine further the moderator role of self-efficacy, two additional studies were designed in Thailand and Germany. Study 1 surveyed 1718 Thai university students in terms of a low-fat diet; Study 2 surveyed 1140 German internet users in terms of their fruit and vegetable consumption at two measurement points in time, 6 months apart. Intentions served as predictor, planning as mediator, self-efficacy as moderator, and behaviors as outcomes. First, intentions were translated into nutrition behaviors by planning. Second, self-efficacy moderated this mediation in both studies: The strength of the mediated effect increased along with levels of self-efficacy, even when accounting for baseline behaviors. For planning to mediate the intention-behavior relation, people must not harbor self-doubts. If they lack self-efficacy, intentions are not well translated into nutrition behavior through planning. PMID- 22044012 TI - Balanced states of mind in psychopathology and psychological well-being. AB - The balanced states of mind (BSOM) model proposes that coping with stress and psychological well-being is a function of the BSOM ratio of positive thoughts to the sum of positive and negative thoughts. Based on different BSOM ratios, different BSOM categories are constructed to quantitatively differentiate levels of coping with stress and psychological well-being. The cognitive content specificity hypothesis states that there are unique themes of semantic content in self-reported automatic thoughts particular to depression or anxiety. This study investigated the BSOM model and its cognitive content-specificity for depression, anxiety, anger, stress, life satisfaction, and happiness, based on negative and positive automatic thoughts. Three hundred and ninety-eight college students from Singapore participated in this study. First, BSOM ratio and positive automatic thoughts were positively correlated with life satisfaction and happiness, and negatively correlated with stress, anxiety, depression, and anger. In contrast, negative automatic thoughts were positively correlated with stress, anxiety, depression, and anger, and negatively correlated with life satisfaction and happiness. Second, levels of psychopathology and psychological well-being were statistically differentiable among the BSOM categories for depression, happiness, perceived stress, and life satisfaction; and less statistically differentiable among the BSOM categories for anxiety and anger, as expected based on the BSOM model and cognitive content-specificity hypothesis. Third, the results were more supportive of the BSOM model for depression, followed by happiness, perceived stress, life satisfaction, anxiety, and anger in terms of percentage of variance accounted for by BSOM categories, as expected based on the cognitive content specificity hypothesis. Taken together, the results suggested that the more moderately positive thoughts one has (balanced by negative thoughts), the better mental health outcomes one has. Implications and limitations of these findings are discussed. PMID- 22044013 TI - Mental health problems among internally displaced persons in Darfur. AB - War victims are regarded as one of the highest risk groups for mental disturbances. This study investigated the effects of the Darfur conflict on mental health of 430 internally displaced persons (IDPs) from three camps located around Fasher and Nyala towns. A stratified random sampling technique was used to select participants. Male participants represented 50.6% of the sample while female participants represented 49.4%. The Posttraumatic Stress Disorder Checklist and the General Health Questionnaire (GHQ-28) were used in addition to a questionnaire measuring demographic variables and living conditions. It was hypothesized that high prevalence of posttraumatic stress disorder (PTSD) symptoms and of nonpsychotic psychiatric symptoms will be evident. Results showed a high dissatisfaction rate (72%) with living conditions among IDPs. There was also high prevalence of PTSD (54%) and general distress (70%) among IDPs. Female participants showed more somatic symptoms than their male counterparts. Married participants were more distressed, anxious, and showed more social dysfunction, while single ones reported more avoidance symptoms. Significant differences related to date of displacement were found in PTSD and hyperarousal. The group of IDPs displaced in 2003 scored higher on these scales than those displaced in 2004 and 2005. There was also significant difference related to date of displacement in distress, somatic symptoms, depression, anxiety, and social dysfunction. IDPs displaced in 2003 scored higher on these scales. Results are discussed in light of the study hypotheses and previous findings. It is concluded that three factors might affect the dissatisfaction of IDPs with living conditions inside camps. These are: lack of employment, unsuitability of food items, and lack of security around camps. It was recommended that psychological support services should be among the prime relief services provided by aid agencies. PMID- 22044014 TI - The moderating effects of gender on the associations between multidimensional hostility and psychosomatic symptoms: a Chinese case. AB - The purpose of this study was to examine the effects of gender on the relationship between multidimensional hostility and psychosomatic symptoms in Chinese culture. The participants in this study were 398 Chinese college students (40% female) recruited from Taiwan. Four dimensions of multidimensional hostility hostility cognition, hostility affect, expressive hostility behavior, and suppressive hostility behavior-were measured by the Chinese Hostility Inventory. After controlling for the effects of depression and anxiety, the results of path analysis revealed that the multidimensional hostility predicted psychosomatic symptoms directly, and predicted psychosomatic symptoms indirectly through negative health behavior. Furthermore, gender moderated the relationships between multidimensional hostility and health outcomes. Expressive hostility exacerbated psychosomatic symptom in females but buffered it in males, while affective hostility exacerbated psychosomatic symptoms in males. Additionally, suppressive hostility behavior was correlated to psychosomatic symptoms indirectly through negative health behavior in females. Moreover, expressive hostility was correlated to psychosomatic symptoms indirectly through negative health behavior more in males than in females. PMID- 22044015 TI - Work stressors, Chinese coping strategies, and job performance in Greater China. AB - The aim of this research was to jointly test effects of work stressors and coping strategies on job performance among employees in the Greater China region. A self administered survey was conducted to collect data from three major cities in the region, namely Beijing, Hong Kong, and Taipei (N = 380). Four important work stressors were assessed: heavy workload, organizational constraints, lack of work autonomy, and interpersonal conflict. We used a four-factor model of Chinese coping strategies composed of hobbies/relaxation, active action, seeking social support, and passive adaptation. Job performance was indicated by both task performance (quantity of work, quality of work, job knowledge) and contextual performance (attendance, getting along with others). We found that: (1) work stressors were related to job performance. Specifically, workload had a positive relation with quantity of work, whereas organizational constraints had negative relations with quantity of work and attendance. In addition, interpersonal conflict had a negative relation with getting along with others. (2) Chinese positive coping strategies were positively related to job performance. Specifically, seeking social support had positive relations with quantity of work and getting along with others, whereas active action had positive relations with attendance and job knowledge. (3) Chinese passive adaptation coping behaviors were negatively related to job performance. Specifically, passive adaptation had negative relations with quantity of work, quality of work, and getting along with others. The present study thus found joint effects of work stressors and coping behaviors among Chinese employees in the Greater China region, encompassing three sub-societies of mainland China, Hong Kong, and Taiwan. Differential effects of Chinese positive and passive coping strategies were also noted. Most importantly, all these effects were demonstrated on multiple indicators of job performance, a rarely studied but important strain variable from the organizational point of view. PMID- 22044016 TI - Linking social axioms with indicators of positive interpersonal, social and environmental functioning in Iran: an exploratory study. AB - Social axioms are people's general beliefs about how the world functions and always involve the relationship between two conceptual entities. Social axioms have been proposed as a construct that can be useful in helping researchers interpret cultures and explain people's behaviors in different cultural contexts. Despite the growth of studies on social axioms in various countries, no effort has been made so far to investigate specifically the relation between social axioms and indicators of interpersonal, social, and environmental functioning. To fill this gap, this exploratory study sought to examine the relation between social axioms and a set of variables indicating positive interpersonal, social, and environmental functioning (namely, gratitude, connectedness to nature, social participation, perspective-taking, and empathic concern) in a sample of 303 Iranian university students. Findings showed that reward for application, religiosity, and social complexity significantly predicted gratitude when sex was controlled for. Social complexity and reward for application significantly contributed to explaining the variance in connectedness to nature over and above sex. Social cynicism and social complexity also predicted perspective-taking significantly after controlling for sex. Social axioms were not successful in predicting social participation and empathic concern. Overall, it is possible to conclude that the findings support the utility of social axioms in predicting interpersonal, social, and environmental functioning. That is, generalized beliefs about oneself, the social and physical environment, or the spiritual world are associated with individuals' interpersonal, social, and environmental functioning in this Iranian sample. PMID- 22044017 TI - Effects of basic human values on host community acculturation orientations. AB - Although literature provides evidence for the relationship between values and acculturation, the relationship between host community acculturation orientations has not yet been investigated. In this study we tested the effects of four high order values (openness to change, self-transcendence, conservation, and self enhancement, devised according to Schwartz's model) on host community acculturation orientations towards immigrants (devised according the interactive acculturation model) in the public domain of employment and the private domain of endogamy/exogamy. Participants were 264 Italian University students, who completed a questionnaire containing the Portrait Values Questionnaire, a measure of personal values, and the Host Community Acculturation Scale, aimed at measuring Italian acculturation strategies towards three groups of immigrants: Immigrants (the general category), Chinese (the valued immigrant group), and Albanians (the devalued immigrant group). Results showed that personal values are related to the adoption of acculturation orientations: In particular, the values that mostly impacted on acculturation orientations were self-transcendence and conservation. Values concerning self-transcendence encourage the adoption of integrationism, integrationism-transformation, and individualism and reduce the adoption of assimilationism, segregationism, and exclusionism. Values concerning conservation encourage the adoption of assimilation, segregation and exclusion orientations and reduce the adoption of both types of integrationism and individualism. Minor effects were found regarding self-enhancement and openness to change. PMID- 22044018 TI - Migration: a concept analysis from a nursing perspective. AB - AIM: This article is a report of a concept analysis of nurse migration. BACKGROUND: International migration is increasing and nurse migrants are active participants in this movement. Migration is a complex term and can be examined from a range of perspectives. Analysis of nurse migration is needed to guide policy, practice and research. DATA SOURCES: A literature search was undertaken using electronic literature indexes, specific journals and websites, internet search engines and hand searches. No timeframe was placed on the search. Most literature found was published between 2001 and 2009. A sample of 80 documents met the inclusion criteria. METHOD: Walker and Avant's approach guided the analysis. DISCUSSION: Nurse migration can be defined by five attributes: the motivation and decisions of individuals; external barriers and facilitators; freedom of choice to migrate; freedom to migrate as a human right, and dynamic movement. Antecedents of migration include the political, social, economic, legal, historical and educational forces that comprise the push and pull framework. The consequences of migration are positive or negative depending on the viewpoint and its affect on the individual and other stakeholders such as the source country, destination country, healthcare systems and the nursing profession. CONCLUSION: This concept analysis clarified the complexities surrounding nurse migration. A nursing-specific middle-range theory was proposed to guide the understanding and study of nurse migration. PMID- 22044019 TI - Potential health hazards associated with exposures to asbestos-containing drywall accessory products: A state-of-the-science assessment. AB - Until the late 1970s, chrysotile asbestos was an ingredient in most industrial and consumer drywall accessory products manufactured in the US. In 1977, the Consumer Product Safety Commission (CPSC) issued a ban of consumer patching compounds containing "respirable, free-form asbestos" based on their prediction of exceptionally high rates of asbestos-related diseases among individuals using patching compounds for as little as a few days. Although hundreds of thousands of workers and homeowners handling these products may have experienced exposure to asbestos prior to the ban, there has been no systematic effort to summarize and interpret the information relevant to the potential health effects of such exposures. In this analysis, we provide a comprehensive review and analysis of the scientific studies assessing fiber type and dimension, toxicological and epidemiological endpoints, and airborne fiber concentrations associated with joint compound use. We conclude that: 1) asbestos in drywall accessory products was primarily short fiber (< 5 um) chrysotile, 2) asbestos in inhaled joint compound particulate is probably not biopersistent in the lung, 3) estimated cumulative chrysotile exposures experienced by workers and homeowners are below levels known to be associated with respiratory disease, and 4) mortality studies of drywall installers have not demonstrated a significantly increased incidence of death attributable to any asbestos-related disease. Consequently, contrary to the predictions of the CPSC, the current weight of evidence does not indicate any clear health risks associated with the use of asbestos-containing drywall accessory products. We also describe information gaps and suggest possible areas of future research. PMID- 22044020 TI - Operation of marine diesel engines on biogenic fuels: modification of emissions and resulting climate effects. AB - The modification of emissions of climate-sensitive exhaust compounds such as CO(2), NO(x), hydrocarbons, and particulate matter from medium-speed marine diesel engines was studied for a set of fossil and biogenic fuels. Applied fossil fuels were the reference heavy fuel oil (HFO) and the low-sulfur marine gas oil (MGO); biogenic fuels were palm oil, soybean oil, sunflower oil, and animal fat. Greenhouse gas (GHG) emissions related to the production of biogenic fuels were treated by means of a fuel life cycle analysis which included land use changes associated with the growth of energy plants. Emissions of CO(2) and NO(x) per kWh were found to be similar for fossil fuels and biogenic fuels. PM mass emission was reduced to 10-15% of HFO emissions for all low-sulfur fuels including MGO as a fossil fuel. Black carbon emissions were reduced significantly to 13-30% of HFO. Changes in emissions were predominantly related to particulate sulfate, while differences between low-sulfur fossil fuels and low-sulfur biogenic fuels were of minor significance. GHG emissions from the biogenic fuel life cycle (FLC) depend crucially on energy plant production conditions and have the potential of shifting the overall GHG budget from positive to negative compared to fossil fuels. PMID- 22044021 TI - Insights into the initiation of type 2 immune responses. AB - Type 2 immune responses, characterized by the differentiation of CD4+ T helper type 2 (Th2) cells and the production of the type 2 cytokines interleukin-4 (IL 4), IL-5, IL-9 and IL-13, are associated with parasitic helminth infections and inflammatory conditions such as asthma and allergies. Until recently the initiating factors associated with type 2 responses had been poorly understood. This review addresses the recent advances in identifying the diverse range of antigens/allergens associated with type 2 responses and the function, expression and sources of type-2-initiating cytokines (thymic stromal lymphopoietin, IL-25 and IL-33). We also discuss the latest findings regarding innate lymphoid cells, such as nuocytes, as early sources of type 2 cytokines and their importance in protective immunity to helminth infections. These developments represent major breakthroughs in our understanding of type 2 immunity, and highlight the increased complexity existing between the innate and adaptive arms of these responses. These additional steps in the type 2 immune pathway also offer potential targets for therapeutic intervention. PMID- 22044022 TI - Catalytic activity trends of oxygen reduction reaction for nonaqueous Li-air batteries. AB - We report the intrinsic oxygen reduction reaction (ORR) activity of polycrystalline palladium, platinum, ruthenium, gold, and glassy carbon surfaces in 0.1 M LiClO(4) 1,2-dimethoxyethane via rotating disk electrode measurements. The nonaqueous Li(+)-ORR activity of these surfaces primarily correlates to oxygen adsorption energy, forming a "volcano-type" trend. The activity trend found on the polycrystalline surfaces was in good agreement with the trend in the discharge voltage of Li-O(2) cells catalyzed by nanoparticle catalysts. Our findings provide insights into Li(+)-ORR mechanisms in nonaqueous media and design of efficient air electrodes for Li-air battery applications. PMID- 22044023 TI - Stage-dependent agreement between cerebrospinal fluid proteins and FDG-PET findings in Alzheimer's disease. AB - Cerebral hypometabolism and abnormal levels of amyloid beta (Abeta), total (t tau) and phosphorylated tau (ptau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer's disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4 +/- 3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Abeta1-42, p-tau181, and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole sample (n=47) and for the subgroups stratified as mild (MMSE > 20 points, n=30) and moderate (MMSE < 21 points, n=17) AD. In the whole patient sample, the agreement with the FDG-PET finding was 77% (chance-corrected kappa [kappa]=0.34, p=0.016) for t-tau, 68% (kappa=0.10, n.s.) for p-tau181, and 68% (kappa=0.04, n.s.) for Abeta1-42. No significant agreement was found in the mild AD subgroup, while there was a strong agreement for t-tau (94%, kappa=0.77, p=0.001) and p-tau181 (88%, kappa=0.60, p=0.014) in the moderate AD group. A significant agreement between the FDG-PET and CSF tau findings in patients with AD supports the view that both are markers of neurodegeneration. CSF tau proteins and FDG-PET might substitute each other as supportive diagnostic tools in patients with suspected moderate-to-severe Alzheimer's dementia, while this is not the case in subjects at an earlier disease stage. PMID- 22044024 TI - Intrahippocampal amyloid-beta (1-40) injections injure medial septal neurons in rats. AB - Alzheimer's disease (AD) is a devastating disorder that leads to memory loss and dementia. Neurodegeneration of cholinergic neurons in the septum and other basal forebrain areas is evident in early stages of AD. Glutamatergic neurons are also affected early in AD. In these stages, amyloid-beta-peptide (Abeta) plaques are present in the hippocampus and other cortices but not in the basal forebrain, which includes the septum. We postulate that early deposition of hippocampal Abeta damages the axon terminals of cholinergic and glutamatergic septo hippocampal neurons, leading to their degeneration. To determine the mechanisms underlying septal degeneration, fibrillar Abeta1-40 was injected into the Cornu Ammonis (CA1) hippocampal region of rats. Controls were injected with reverse peptide Abeta40-1. A 16% reduction in NeuN+ cells was observed around the injection sites when compared to controls (p < 0.05) one week after injections. Stereology was used to estimate the number of choline acetyl transferase (ChAT), glutamate and glutamic acid decarboxylase 67 (GAD67) immunoreactive septal neurons. Medial septal ChAT and glutamate immunoreactive neurons were reduced 38% and 26%, respectively by hippocampal injections of Abeta1-40 peptide in relation to controls. In contrast, the number of GAD67 inmunoreactive neurons was not significantly reduced. Apoptotic cells were detected in the medial septal region of Abeta1-40 treated animals but not in controls. These results indicate that limited Abeta-induced hippocampal lesions lead to an overall damage of vulnerable septal neuronal populations, most likely by Abeta interaction with septo hippocampal axon terminals. Thus, axon terminals constitute an important target for novel therapeutics dedicated to control Abeta-induced toxicity. PMID- 22044025 TI - Altered calmodulin degradation and signaling in non-neuronal cells from Alzheimer's disease patients. AB - Previous work indicated that changes in Ca(2+)/calmodulin (CaM) signaling pathway are involved in the control of proliferation and survival of immortalized lymphocytes from Alzheimer's disease (AD) patients. We examined the regulation of cellular CaM levels in AD lymphoblasts. An elevated CaM content in AD cells was found when compared with control cells from age-matched individuals. We did not find significant differences in the expression of the three genes that encode CaM: CALM1, 2, 3, by real time RT-PCR. However, we observed that the half-life of CaM was higher in lymphoblasts from AD than in control cells, suggesting that degradation of CaM is impaired in AD lymphoblasts. The rate of CaM degradation was found to be dependent on cellular Ca(2+) and ROS levels. CaM degradation occurs mainly via the ubiquitin-proteasome system. Increased levels of CaM were associated with overactivation of PI3K/Akt and CaMKII. Our results suggest that increased levels of CaM synergize with serum to overactivate PI3K/Akt in AD cells by direct binding of CaM to the regulatory alpha-subunit (p85) of PI3K. The systemic failure of CaM degradation, and thus of Ca(2+)/CaM-dependent signaling pathways, may be important in the etiopathogenesis of AD. PMID- 22044026 TI - Association of SORL1 alleles with late-onset Alzheimer's disease. findings from the GIGAS_LOAD study and mega-analysis. AB - The pathophysiology of Alzheimer's disease (AD) is influenced by sorting-protein related receptor (sorLa) that is less expressed in AD patients. The gene encoding sorLa (SORL1) has been investigated as a susceptibility factor for late-onset AD (LOAD) with conflicting results. Our objectives were to confirm the association between SORL1 SNPs and LOAD in two independent South-European centers and to perform a mega-analysis of published samples. We analyzed three SORL1 SNPs (intron 6: rs668387; rs689021; rs641120) from the Greece-Italy Genetic Association Study on lateonset AD (GIGAS_LOAD). Greek sample included 96 patients with LOAD (DSM-IV) and 120 unrelated controls. In Italy, a community-based sample is ongoing. 47 LOAD patients and 165 controls were recruited until study endpoint. These samples and previously published ones (Alzgene) were pooled as in a single study. A test for trend was used to analyze genotype association. In the GIGAS_LOAD sample no association was detected between SORL1 genotypes and LOAD. Conversely all SNPs were associated with LOAD in mega-analysis based on ordinal classification of genotypes (Armitage's test: p < 0.001). Although our analysis of pooled samples has positive results for the association between SORL1 and AD, there is substantial heterogeneity across studies. Thus further examination into SORL1 SNPs and the population is necessary to determine the role of SORL1 in LOAD. PMID- 22044027 TI - Tissue distribution and pharmacodynamics of rivastigmine after intranasal and intravenous administration in rats. AB - The aim of the study was mainly to investigate the relationship between concentration of rivastigmine and its inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) following intranasal (IN) and intravenous (IV) administration in rats, and to provide a novel nasal delivery route for the brain disease therapy. Rivastigmine was administered to male rats at 2 mg/kg by IN and IV route. Drug concentration, AChE and BuChE activity were measured in the plasma, central nervous system (CNS) regions i.e. olfactory region, hippocampus, cerebrum and cerebellum, and peripheral tissues. It was determined that rivastigmine was characterized by extremely rapid and complete absorption into the systemic circulation followed by a rapid decline in the plasma concentrations, and can also quickly distribute into CNS and peripheral tissues by the two routes. IN administration showed higher concentration in CNS regions and longer action on inhibiting the activity of AChE and BuChE than IV administration. More significant decrease of the two enzymes was observed in CNS regions than in peripheral tissues for both administrations. A close relationship was found between the concentration of rivastigmine and enzyme inhibition in plasma and CNS tissues in rats. Based on these findings, it was concluded that rivastigmine could cause relatively strong inhibition of AChE and BuChE in plasma and brain tissues, especially in hippocampus, cortex and cerebrum. The pharmacodynamics was closely related to its concentration in vivo. The intranasal route can be strategy for delivering the drug into brain. PMID- 22044028 TI - The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population. AB - OBJECTIVE: Methotrexate (MTX) is the first-choice drug for the treatment of rheumatoid arthritis (RA) patients. However, 30% of RA patients discontinue therapy within 1 year, usually because of adverse effects. Previous studies have reported conflicting results on the association of polymorphisms in the MTHFR gene with the toxicity of MTX in RA. The aim of this study was to assess the involvement of the C677T and A1298C polymorphisms in the MTHFR gene in the toxicity of MTX in a Spanish RA population. METHODS: The study included retrospectively 468 Spanish RA patients treated with MTX. Single nucleotide polymorphism (SNP) genotyping was performed using the oligonucleotide microarray technique. Allele and genotype association analyses with regard to MTX toxicity and a haplotype association test were also performed. RESULTS: Eighty-four out of the 468 patients (18%) had to discontinue therapy due to adverse effects or MTX toxicity. The C677T polymorphism (rs1801133) was associated with increased MTX toxicity [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.01-1.98, p = 0.0428], and the strongest association was shown in the recessive model (OR 1.95, 95% CI 1.08-3.53, p = 0.0246). The A1298C polymorphism (rs1801131) was not associated with increased MTX toxicity (OR 0.94, 95% CI 0.65-1.38, p = 0.761). A borderline significant risk haplotype was found: 677T-1298A (OR 1.40, 95% CI 1.00 1.96, p = 0.0518). CONCLUSION: These results demonstrate that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in a Spanish RA population. PMID- 22044029 TI - Antibacterial performance of polydopamine-modified polymer surfaces containing passive and active components. AB - A growing number of device-related nosocomial infections, elevated hospitalization costs, and patient morbidity necessitate the development of novel antibacterial strategies for clinical devices. We have previously demonstrated a simple, aqueous polydopamine dip-coating method to functionalize surfaces for a wide variety of uses. Here, we extend this strategy with the goal of imparting antifouling and antimicrobial properties to substrates, exploiting the ability of polydopamine to immobilize polymers and induce metal nanoparticle formation. Polydopamine was deposited as a thin adherent film of 4 nm thickness from alkaline aqueous solution onto polycarbonate substrates, followed by grafting of antifouling polymer polyethylene glycol and in situ deposition of silver nanoparticles onto the polydopamine coated polycarbonate substrates. Elemental and morphological surface analyses confirmed successful grafting of polyethylene glycol brushes onto polydopamine-coated substrates, as well as spontaneous silver nanoparticle formation for polydopamine-coated substrates incubated in silver nitrate solutions. Sustained silver release was observed over at least 7 days from silver-coated substrates, and the release kinetics could be modulated via additional polydopamine overlayers. In vitro functional assays employing gram negative and positive strains demonstrated dual fouling resistance and antibacterial properties of the coatings due to the fouling resistance of grafted polyethylene glycol and antibacterial effect of silver, respectively. Polycarbonate substrates coated only with silver using a method similar to existing commercial coatings provided an antibacterial effect but failed to inhibit bacterial attachment. Taking into account the previously demonstrated substrate versatility of polydopamine coatings, our findings suggest that this strategy could be implemented on a variety of substrate materials to simultaneously improve antifouling and antimicrobial performance. PMID- 22044030 TI - Antioxidant inhibitors potentiate the cytotoxicity of photodynamic therapy. AB - Photodynamic therapy (PDT) is an increasingly popular anticancer treatment that uses photosensitizer, light and tissue oxygen to generate cytotoxic reactive oxygen species (ROS) within illuminated cells. Acting to counteract ROS-mediated damage are various cellular antioxidant pathways. In this study, we combined PDT with specific antioxidant inhibitors to potentiate PDT cytotoxicity in MCF-7 cancer cells. We used disulphonated aluminium phthalocyanine photosensitizer plus various combinations of the antioxidant inhibitors: diethyl-dithiocarbamate (DDC, a Cu/Zn-SOD inhibitor), 2-methoxyestradiol (2-ME, a Mn-SOD inhibitor), l buthionine sulfoximine (BSO, a glutathione synthesis inhibitor) and 3-amino-1,2,4 triazole (3-AT, a catalase inhibitor). BSO, singly or in combination with other antioxidant inhibitors, significantly potentiated PDT cytotoxicity, corresponding with increased ROS levels and apoptosis. The greatest potentiation of cell death over PDT alone was seen when cells were preincubated for 24 h with 300 MUM BSO plus 10 mM 3-AT (1.62-fold potentiation) or 300 MUM BSO plus 1 MUM 2-ME (1.52 fold), or with a combination of all four inhibitors (300 MUM BSO, 10 mM 3-AT, 1 MUM 2-ME and 10 MUM DDC: 1.4-fold). As many of these inhibitors have already been clinically tested, this work facilitates future in vivo studies. PMID- 22044031 TI - Advanced Life Support in Obstetrics (ALSO) and post-partum hemorrhage: a prospective intervention study in Tanzania. PMID- 22044032 TI - Fabrication of surfaces with extremely high contact angle hysteresis from polyelectrolyte multilayer. AB - High contact angle hysteresis on polyelectrolyte multilayers (PEMs) ion-paired with hydrophobic perfluorooctanoate anions is reported. Both the bilayer number of PEMs and the ionic strength of deposition solutions have significant influence on contact angle hysteresis: higher ionic strength and greater bilayer number cause increased contact angle hysteresis values. The hysteresis values of ~100 degrees were observed on smooth PEMs and pinning of the receding contact line on hydrophilic defects is implicated as the cause of hysteresis. Surface roughness can be used to further tune the contact angle hysteresis on the PEMs. A surface with extremely high contact angle hysteresis of 156 degrees was fabricated when a PEM was deposited on a rough substrate coated with submicrometer scale silica spheres. It was demonstrated that this extremely high value of contact angle hysteresis resulted from the penetration of water into the rough asperities on the substrate. The same substrate hydrophobized by chemical vapor deposition of 1H,1H,2H,2H-perfluorooctyltriethoxysilane exhibits high advancing contact angle and low hysteresis. PMID- 22044033 TI - Pre-procedural Elevated White Blood Cell Count and Neutrophil-Lymphocyte (N/L) Ratio are Predictors of Ventricular Arrhythmias During Percutaneous Coronary Intervention. AB - AIMS: The absolute white blood cell (WBC) count and neutrophil to lymphocyte (N/L) ratio are predictors of death/myocardial infarction in patients who have undergone coronary angiography. We hypothesized that a pre-procedural elevated WBC count and an elevated N/L ratio would be a predictor of development of significant ventricular arrhythmias in subjects undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: We retrieved the data for all patients developing ventricular arrhythmia during PCI between 1999 to 2009 from our cath lab database (from 30,798 records), a total of 70 patients (Group I), and tabulated their WBC counts and absolute neutrophil and lymphocyte counts as well as N/L ratios. We compared the data with a random group of age, gender, medications and pre-existing condition matched controls (n=70) (Group II). We also adjusted for amount of myocardium under jeopardy. Group I had a significantly higher total WBC count (means 14,344 Vs 6852; 95% CI; p=0.0004); neutrophil count (means 75.79% Vs 58.06%; 95% CI; p < 0.0001) and N/L ratio (means 3.79 Vs 1.56; 95% CI; p < 0.0001) [means compared with t test]. CONCLUSION: Our data suggests a pre-procedural elevated WBC count, neutrophils and elevated N/L ratio are predictors of significant ventricular arrhythmias in patients undergoing percutaneous coronary intervention (PCI). PMID- 22044034 TI - Fibrosis, Enzymatic and Non-Enzymatic Cross-Links in Hypertensive Heart Disease. AB - Myocardial fibrosis is commonly observed in left ventricular (LV) hypertrophied heart during Arterial Hypertension. This pathological change coupled with vascular stiffening with aging and diabetes may reduce the cardiovascular system elasticity contributing to the functional impairment. Both the LV adaptive response to the increasing blood pressure and the oxidative damage contribute to myocardial fibrosis; in particular, reactive oxygen species (ROS) induce the formation of reactive electrophilic carbonyl species by reacting with lipids and sugars which in turn react with proteins forming irreversible adducts (AGEs, ALEs and EAGLEs) and cross-links. The vascular wall matrix then becomes less distensible, as the formation of the adducts induces greater capacity in collagen to resist normal turnover. Therefore, monitoring cardiac fibrosis and markers of collagen synthesis, degradation and non-enzymatic cross-linking and the use of drugs that revert collagen accumulation and/or prevent/repair non-enzymatic cross linking might represent a novel opportunity to alter the natural history of hypertensive heart disease. Recent evidences have suggested to target the excess of collagen cross-links; initial evidence seems to show that fibrosis is not affected to the same degree by all anti-hypertensive agents. ACEI and ARBs appear particularly effective. Finally, agents acting as cross-link breakers on AGEs or preventing AGEs formation or affecting the TTG activity are emerging. PMID- 22044035 TI - LPS In Patients With Left Ventricular Dysfunction Of Ischemic And Non-Ischemic Origin. AB - BACKGROUND: We decided to examine whether there are differences in the levels of lipopolysaccharide (LPS) in various groups of patients suffering from left ventricular dysfunction, requiring no intravenous therapy. MATERIALS AND METHODS: We studied 37 patients (ranging from 39 to 80 years, mean age of 59.8 years, SD 9.5) with left ventricular dysfunction caused by dilated cardiomyopathy, valvular heart disease or chronic ischemic cardiomyopathy. These patients were compared to 29 healthy subjects and 7 acute myocardial infarction (AMI) patients. The LPS levels were analyzed and correlated to the echocardiographic index of left ventricular impairment and to the clinical parameters. RESULTS: The plasma levels of LPS were lower in patients with a chronic LV dysfunction than in the control group but without reaching any statistical significance (chronic LV dysfunction patients 6.33+/-5.03 pg/ml, AMI patients 13.58+/-19.14 pg/ml, healthy controls 11.12+/-12.97 pg/ml). The values observed in AMI patients were similar to those of the control group, without any significant differences. No significant correlation of the LPS levels was obseved either with the echocardiographic index of left ventricular impairment or with the clinical parameters. CONCLUSIONS: It is probable that LPS does not play any major role in the progression of LV dysfunction. The possible role of LPS in critical heart failure should therefore be better evaluated. PMID- 22044036 TI - Anti-Platelet Therapy for Acute Coronary Syndrome: A Review of Currently Available Agents and What the Future Holds. AB - Dual anti-platelet therapy remains a cornerstone in the management of patients suffering from acute coronary syndromes (ACS). The combination of aspirin and clopidogrel has been shown to result in significant reductions in cardiovascular end points including recurrent infarction and death in several randomised control trial of patients with ACS. However, many patients still experience ischaemic events on the combination of aspirin and clopidogrel. Aspirin is a relatively weak anti platelet agent. Clopidogrel is a pro drug that required activation by hepatic metabolism and hence its onset of action is delayed; there is genetic variation in the clinical response to the drug, the platelet inhibition is irreversible and no intravenous form is available. Consequently new anti-platelet agents have been developed to address the short falls of this combination therapy. This paper discusses existing anti-platelet regimes and focuses on novel antiplatelet agents that are currently under clinical evaluation. PMID- 22044037 TI - Pexelizumab, an Anti-C5 Complement Antibody for Primary Coronary Revascularization: A New Insight from Old Versions. AB - Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to reduce reperfusion injury after coronary revascularization in acute myocardial infarction and severe coronary artery disease had been approved in animal studies and further demonstrated clinical benefits in phase II study: the COMMA trial and phase III study: the PRIMOCABG trial. However, the negative results of pexelizumab were observed in the COMPLY trial and the APEX-AMI trial. In the APEX AMI trial, the effectiveness of pexelizumab has reasoned to be prominent in high risk patients. Similarly, an exploratory analysis of the combined PRIMO-CABG I and II data set using an established predictive risk model demonstrated a mortality benefit for high-risk surgical patients. Accordingly, the result of these trials supported a moderational model to explain the usefulness of pexelizumab affected by the baseline risk profiles of patients. In this regard, we have commented that pexelizumab may be hazardous to patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention without using adequate anti-thrombotic agents (glycoprotein IIb-IIIa antiplatelet inhibitors, clopidogrel and haparin non-responders) according to the results of the experiment by professor Roger and coworkers and the mathematic estimations of the relative risks. Herein, we proposed a mediational model to account for the effectiveness of pexelizumab. PMID- 22044038 TI - Malignancy and Radiation-Induced Cardiotoxicity. AB - Mediastinal mass radiotherapy as adjuvant or primary treatment is usually performed for lung, breast and oesophagus cancer, for lymphoma and thymoma. However, untoward late cardiac and vascular adverse effects can develop that were underrecognized in the past because a very long latency from exposure to clinical manifestations is needed. Moreover, the true cumulative incidence of these complications is hard to correctly evaluate. Thoracic Radiotherapy (TR) may determine pathological involvement of pericardium, myocardium, cardiac valves, conduction system, coronary arteries and of subclavian and carotid arteries. The main clinical features of radiation induced cardiac and vascular diseases are discussed in the review. Recently, an increased risk of strokes and transient ischemic attacks (TIAs) has also been shown after TR, and the possible mechanisms as well as the measures useful in decreasing the risk are discussed. Other emerging aspects of radiation induced damages, just like malfunction of Pace Maker and of Implantable Defibrillators as well as malfunction of coronary bypass and coronary stents, probably will become more frequent in the next future. Finally, the current knowledge concerning the effects of the new modalities of administration of TR (doses, techniques) on the cardiovascular risk is reported, as well as the important clinical problem linked to the appropriate evaluation of the risk/benefit ratio of performing TR in different clinical situations. PMID- 22044039 TI - Regulation of Endothelial Nitric Oxide Synthase in Pathophysiological Conditions. AB - The nitric oxide (NO) cascade and endothelial NO synthase (eNOS) are best known for their role in endothelium-mediated relaxation of vascular smooth muscle (VSM). NO generated by eNOS has been established as a key regulatory signaling molecule in the vasculature. The activities of eNOS are controlled by intracellular calcium/calmodulin (CaM) and by binding of the molecular chaperone heat-shock protein 90 (Hsp90). A number of studies have demonstrated a close association between insulin resistance (IR) and NO bioactivity. Some recent studies demonstrate that insulin signaling is essential for normal cardiovascular (CV) function and lack of it such as IR result in CV dysfunction and disease. A key step in the initiation and progression of atherosclerosis is a reduction in the bioactivity of endothelial cell-derived NO. Multiple changes in endothelial function and eNOS activity accompany the onset and development of Type 2 diabetes mellitus (T2DM) and contribute to the development of cardiovascular disease (CVD). This review focuses on recent findings about regulation of eNOS in pathophysiological conditions such are: IR, T2DM and CVD. PMID- 22044040 TI - Ox-LDL Particles: Modified Components, Cellular Uptake, Biological Roles and Clinical Assessments. AB - Among concepts proposed to elucidate atherosclerosis process, the oxidative modification hypothesis is more considered to be investigated in studies. Based on the hypothesis, the LDL components are chemically modified due to oxidative stress within subendothelial space of vessels. The cells are able to recognize the oxidized LDL (ox-LDL) preparations so that inflammatory events spread through intracellular pathways and lead to the cellular dysfunction and the production of atherosclerotic plaques. The circulating ox-LDL level is suggested as biomarker of atherogenic lesions. However, it is not confirmed in some studies since the circulating ox-LDL clearance during the extent of atherosclerosis process is related to function of scavenger receptors and the serum anti LDL levels. The report is focused on the biochemical characteristics of modified LDL components, the cellular internalization of ox-LDL particles through the scavenger receptors, prediction of consensus blocks in the receptor sequences and the circulating ox LDL assessments in cardiovascular complications. PMID- 22044041 TI - Structural and biophysical determinants of alphabeta T-cell antigen recognition. AB - The molecular rules that govern MHC restriction, and allow T-cells to differentiate between peptides derived from healthy cells and those from diseased cells, remain poorly understood. Here we provide an overview of the structural constraints that enable the T-cell receptor (TCR) to discriminate between self and non-self peptides, and summarize studies that have attempted to correlate the biophysical parameters of TCR/peptide-major histocompatibility complex (pMHC) binding with T-cell activation. We further review how the antigenic origin of peptide epitopes affects TCR binding parameters and the 'quality' of a T-cell response. Understanding the principles that govern pMHC recognition by T-cells will unlock pathways to the rational development of immunotherapeutic approaches for the treatment of infectious disease, cancer and autoimmunity. PMID- 22044042 TI - Importance of steric effects on the efficiency and fidelity of transcription by T7 RNA polymerase. AB - DNA-dependent RNA polymerases such as T7 RNA polymerase (T7 RNAP) perform the transcription of DNA into mRNA with high efficiency and high fidelity. Although structural studies have provided a detailed account of the molecular basis of transcription, the relative importance of factors like hydrogen bonds and steric effects remains poorly understood. We report herein the first study aimed at systematically probing the importance of steric and electrostatic effects on the efficiency and fidelity of DNA transcription by T7 RNAP. We used synthetic nonpolar analogues of thymine with sizes varying in subangstrom increments to probe the steric requirements of T7 RNAP during the elongation mode of transcription. Enzymatic assays with internal radiolabeling were performed to compare the efficiency of transcription of modified DNA templates with a natural template containing thymine as a reference. Furthermore, we analyzed effects on the fidelity by measuring the composition of RNA transcripts by enzymatic digestion followed by two-dimensional thin layer chromatography separation. Our results demonstrate that hydrogen bonds play an important role in the efficiency of transcription but, interestingly, do not appear to be required for faithful transcription. Steric effects (size and shape variations) are found to be significant both in insertion of a new RNA base and in extension beyond it. PMID- 22044043 TI - A phaeochromocytoma occurring in a patient with Parkinson's disease on L-dopa therapy: a diagnostic challenge. PMID- 22044044 TI - Oxidative stress in preretinopathic diabetes subjects and antioxidants. AB - BACKGROUND: This study assessed the effect of a systemic oral treatment with antioxidants (AOs) in preretinopathic diabetes (PRD) patients, through the evaluation of oxidative stress in plasma and changes in the full-field electroretinogram (ERG). METHODS: Thirty-two PRD subjects with good metabolic control were recruited. Patients were randomized in two groups, one of which received oral AO treatment with alpha-lipoic acid at 400 mg/day in association with genistein and vitamins, whereas the other group received a placebo. Free radicals and the AO barrier were evaluated in plasma with the Free Radical Analytical System 4 instrument (H&D srl, Parma, Italy), and the same day the electrophysiological response was measured by ERG. These analyses were performed at enrollment and after 30 days of treatment. RESULTS: Statistically significant increases of plasma AO levels and ERG oscillatory potential values were observed in the group treated with AO, but not in the control group. CONCLUSIONS: Results of this preliminary study suggest that an oral treatment with AOs in PRD subjects may have a protective effect on retinal cells, as detected by ERG analysis, through the strengthening of the plasma AO barrier. PMID- 22044046 TI - Critiquing fetal alcohol syndrome health communication campaigns targeted to American Indians. AB - It is widely recognized American Indians and Alaska Natives have suffered from far worse health status than that of other Americans. Health communication campaigns directed to American Indians and Alaska Natives and their outcomes must be grounded in an understanding of the historical and ongoing marginalization and cultural dislocation of these groups. The authors draw upon the specific case of health communication campaigns to reduce cases of fetal alcohol syndrome among American Indians and Alaska Natives. Counteracting stereotyping of American Indians and alcohol consumption by mainstream American popular culture and mediated discourses, coverage of fetal alcohol syndrome in the media is assessed. The study analyzes 429 American Indian news articles from 1990 to 2010. Mainstream American and American Indian media should cover health concerns such as fetal alcohol syndrome more extensively. Researchers, health communication campaign developers, health policy makers, and mainstream media must be knowledgeable about American Indian and Alaskan Native identity, cultures, and history, and diversity across Nations. Last, and most important, health communication strategists and health policy makers must welcome American Indians and Alaska Natives to take leadership roles in communicating culture- and Nation specific health campaign strategies to eliminate health disparities. PMID- 22044047 TI - Work engagement in nursing: a concept analysis. AB - AIM: This article is a report of an analysis of the concept of work engagement. Background. Work engagement is the central issue for 21st century professionals and specifically for registered nurses. Conceptual clarity about work engagement gives empirical direction for future research and a theoretical underpinning for the myriad studies about nurses and their work environment. METHOD: Walker and Avant's method of concept analysis was used. Nursing, business, psychology and health sciences databases were searched using Science Direct, CINAHL, OVID, Academic One File, ABI INFORM and PsycINFO for publications that were: written in English, published between 1990 and 2010, and described or studied work engagement in any setting with any population. RESULTS: Work engagement is a positive, fulfilling state of mind about work that is characterized by vigour, dedication and absorption. Trust (organizationally, managerially and collegially) and autonomy are the antecedents of work engagement. The outcomes of nurses' work engagement are higher levels of personal initiative that are contagious, decreased hospital mortality rates and significantly higher financial profitability of organizations. CONCLUSION: When work engagement is conceptually removed from a transactional job demands-resources model, the relational antecedents of trust and autonomy have greater explanatory power for work engagement in nurses. Untangling the antecedents, attributes and outcomes of work engagement is important to future research efforts. PMID- 22044045 TI - Electrochemical sensors and biosensors. PMID- 22044048 TI - Catalytic asymmetric construction of spirocyclopentaneoxindoles by a combined Ru catalyzed cross-metathesis/double Michael addition sequence. AB - Biologically important and synthetically challenging spirocyclopentaneoxindoles with four contiguous stereocenters including one spiroquaternary stereocenter have been constructed in good yields (72-87%) with excellent diastereoselectivity (16:1->30:1 dr) and enantioselectivity (93->99% ee) by a combined Ru-catalyzed cross-metathesis/organocatalyzed asymmetric double-Michael addition sequence. PMID- 22044049 TI - Understanding the roles of basophils: breaking dawn. AB - Early studies that used parasite-infected interleukin-4 (IL-4) reporter animals led us to identify basophils as the primary source of IL-4 and hence propose the hypothesis that basophils trigger the development of antigen-specific T helper type 2 (Th2) immune responses in vivo. These findings appeared to resolve a long standing puzzle underlying Th2 immunity, that is, 'what is the source of the initial IL-4 necessary for CD4 T-cell differentiation into Th2 effector cells?'. However, results from extensive investigations of the contribution of basophils to Th2 immunity unveiled some controversial data that cast doubt on the initial hypothesis. In this review, the consensus and the controversy regarding the roles of basophils in infection and immunity, as well as outstanding questions for the future, are discussed. PMID- 22044050 TI - Manipulation of Forster energy transfer of coupled fluorophores through biotransformation by Pseudomonas resinovorans CA10. AB - An alkyne-terminated anthracene and azide-terminated carbazole were joined through a copper-catalyzed cycloaddition to form a joined donor/acceptor pair. The photonic pair exhibited energy transfer when excited at the peak absorbance of carbazole and fluoresced with an anthracene spectral response. The fluorescent behavior was confirmed as Forster energy transfer (FRET). The lysate of Pseudomonas resinovorans CA10, a member of a predominant group of soil microorganisms that can metabolize a host of substrates, was employed to degrade the pair and alter the luminance spectral characteristics. The FRET was diminished and the corresponding, individual fluorescence of carbazole and anthracene returned. This general approach may find applications in single-cell metabolic studies and bioactivity assays. PMID- 22044051 TI - Scleroderma renal crisis in a Swedish systemic sclerosis cohort: survival, renal outcome, and RNA polymerase III antibodies as a risk factor. AB - OBJECTIVES: To study survival, renal outcome, and RNA polymerase III antibodies (RNAP Abs) as a risk factor for scleroderma renal crisis (SRC) in a Swedish cohort of systemic sclerosis (SSc) patients. METHODS: SRC was diagnosed in 16 SSc patients during the period from 1982 to 2010. For comparison, 112 (seven for each SRC patient) SSc patients without SRC were included. RNAP Abs were detected by a fully automated fluoroenzyme immunoassay (EliA). Values greater than 15 MUg/L were considered positive. Frozen serum samples from the time of diagnosis of SSc were used. RESULTS: The 5- and 10-year survival rates were, respectively, 58% and 40% for SRC patients and 90% and 76% for patients without SRC (p < 0.001). The odds ratio (OR) for mortality was 4.39 [95% confidence interval (CI) 2.10-9.16, p < 0.001] in patients with SRC compared to those without SRC. Renal outcome was good in three patients. Haemodialysis was started in 10 patients and peritoneal dialysis in three. Renal function improved in three patients and dialysis was terminated. Four patients underwent renal transplantation. Seven SRC patients and nine without SRC were positive for RNAP Abs. Anti-RNAP Abs was a strong predictor of SRC. The sensitivity and specificity for development of SRC were 0.44 and 0.92, respectively. The OR for development of SRC was 8.90 (95% CI 2.68-29.6, p = 0.001) in RNAP-positive patients. CONCLUSIONS: RNAP positivity is a strong risk factor for SRC. Renal outcome was variable and survival is still notably decreased. PMID- 22044052 TI - The effect of acute stress exposure on ischemia and reperfusion injury in rat heart: role of oxytocin. AB - Previous studies showed the protective effects of oxytocin (OT) on myocardial injury in ischemic and reperfused rat heart. Moreover, exposure to various stressors not only evokes sudden cardiovascular effects but also triggers the release of OT in the rat. The present study was aimed to evaluate the possible cardioprotective effects of endogenous OT released in response to stress (St), and effects of administration of exogenous OT on the ischemic-reperfused isolated heart of rats previously exposed to St. Wistar rats were divided into six groups: ischemia/reperfusion (IR); St: rats exposed to swim St for 10 min before anesthesia; St+atosiban (ATO): an OT receptor antagonist, was administered (1.5 mg/kg i.p.) prior to St; St+OT: OT was administered (0.03 mg/kg i.p.) prior to St; OT: OT was administrated prior to anesthesia; ATO was given prior to anesthesia. Isolated hearts were perfused with Krebs buffer solution by the Langendorff method and subjected to 30 min of regional ischemia followed by 60 min of reperfusion. The infarct size (IS) and creatine kinase MB isoenzyme (CK MB) and lactate dehydrogenase (LDH) in coronary effluent were measured. Hemodynamic parameters were recorded throughout the experiment. The plasma concentrations of OT and corticosterone were significantly increased by St. Unexpectedly St decreased IR injury compared with the IR alone group. OT administration significantly inhibited myocardial injury, and administration of ATO with St abolished recovery of the rate pressure product, and increased IS and levels of CK-MB and LDH. These findings indicate that activation of cardiac OT receptors by OT released in response to St may participate in cardioprotection and inhibition of myocardial IR injury. PMID- 22044053 TI - Genomics and transcriptomics across the diversity of the Nematoda. AB - The diversity of biology in nematodes is reflected in the diversity of their genomes. Parasitic species in particular have evolved mechanisms to invade and outwit their hosts, and these offer opportunities for the development of control measures. Genomic analyses can reveal the molecular underpinnings of phenotypes such as parasitism and thus, initiate and support research programmes that explore the manipulation of host and parasite physiologies to achieve favourable outcomes. Wide sampling across nematode diversity allows phylogenetically informed formulation of research hypotheses, identification of core features shared by all species or important evolutionary novelties present in isolated clades. Many nematode species have been investigated through the use of the expressed sequence tag approach, which samples from the transcribed genome. Gene catalogues generated in this way can be explored to reveal the patterns of expression associated with parasitism and candidates for testing as drug targets or vaccine components. Analysis environments, such as NEMBASE facilitate exploitation of these data. The development of new high-throughput DNA-sequencing technologies has facilitated transcriptomic and genomic approaches to parasite biology. Whole genome sequencing offers more complete catalogues of genes and assists a systems approach to phenotype dissection. These efforts are being coordinated through the 959 Nematode Genomes initiative. PMID- 22044054 TI - International-local remuneration differences across six countries: do they undermine poverty reduction work? AB - Despite the rhetoric of a single global economy, professionals in poorer countries continue to be remunerated differently depending on whether they are compensated at a local vs. international rate. Project ADDUP (Are Development Discrepancies Undermining Performance?) surveyed 1290 expatriate and local professionals (response rate = 47%) from aid, education, government, and business sectors in (1) Island Nations (Papua New Guinea, Solomon Islands), (2) landlocked economies (Malawi, Uganda), and (3) emerging economies (India, China). Difference in pay was estimated using purchasing power parity, from the World Bank's World Development Indicators 2007. Psychological measures included self-reported pay and benefits (remuneration), self-attributed ability, remuneration comparison, sense of justice in remuneration, remuneration-related motivation, thoughts of turnover and thoughts about international mobility. We included control measures of candour, culture shock, cultural values (horizontal/vertical individualism/collectivism), personality (from the "big five"), job satisfaction and work engagement. Controlling for these and country (small effects) and organization effects (medium), (a) pay ratios between international and local workers exceeded what were perceived to be acceptable pay thresholds among respondents remunerated locally; who also reported a combination of a sense of relative (b) injustice and demotivation; which (c) together with job satisfaction/work engagement predicted turnover and international mobility. These findings question the wisdom of dual salary systems in general, expose and challenge a major contradiction between contemporary development policy and practice, and have a range of practical, organizational, and theoretical implications for poverty reduction work. PMID- 22044055 TI - Remuneration discrepancies in the landlocked economies of Malawi and Uganda. AB - Although the original study of remuneration differences between local and expatriate development workers took place in the landlocked economy of Malawi, the study has never been replicated outside of one sector and organization (the National University), and took place prior to the 2000 Millennium Development Goals. Participating in the present studies were 458 aid and development professionals, working across a range of sectors in Malawi (n = 241, response rate = 50%) and Uganda (n = 217, response rate = 51%). The size of the gap between local and international workers, measured using the World Bank's purchasing power parity, was higher in Malawi (4.04:1) than in Uganda (1.97:1). The ratio was more clearly within tolerance levels in Uganda than in Malawi. Consistent with these differences, and controlling for organization, cultural, and demographic factors, locally remunerated workers reported more and expatriate workers less injustice and demotivation in Malawi than in Uganda. Although sample sizes for the internationally remunerated are small, the findings suggest that wider disparities may (1) hinder perspective-taking and (2) decrease motivation. In-country workshops with stakeholders and subject-matter experts considered the findings, and potential solutions offered through the survey form. They recommended the implementation of performance-based remuneration, including competency-based job analysis and evaluation. Competencies in such functions can be provided by humanitarian work psychology. PMID- 22044056 TI - Remuneration disparities in Oceania: Papua New Guinea and Solomon Islands. AB - This paper explores the impact of remuneration differences on workers in the Solomon Islands and Papua New Guinea. In these countries remunerative differences are linked to government policy (in Papua New Guinea) and job contracts (in the Solomon Islands), and have impacted on industrial relations in both settings (strike action). A total of N = 350 professionals (n = 60 expatriates) from 54 organizations in aid, government, higher education and industry (mean response rate = 36%) responded to an organizational survey form. Remuneration ratios between international and local respondents based on the World Bank's index of purchasing power parity approached 9:1. In both sites staff compared pay and benefits (remuneration) packages: Internationally remunerated staff rated their ability higher than their local counterparts did; locally remunerated groups reported more injustice in remuneration, were more demotivated by the gaps, and were more likely to be thinking about leaving the organization. In-country workshops of N = 40 largely local stakeholders from aid and community organizations plus government ministries considered the survey's findings and recommended: in Solomon Islands, (a) introducing a policy of localization, (b) establishing a remuneration commission (already existent in Papua New Guinea), and (c) reducing the remunerative gap; in Papua New Guinea, (d) reversing the post-Independence "dual pay system" (currently official policy), (e) instituting pay-for-performance, and (f) ensuring the existent localization policy is applied to recruitment, selection, and staff career planning and management. PMID- 22044057 TI - Remuneration differences in the emerging economies of China and India. AB - Emerging economies by definition tend to be less dependent on expatriate skills and labour than lower-income countries, yet remuneration (pay plus benefits) differences between expatriate and local workers persist in them to some degree. According to relative deprivation theory, economic development paradoxically elevates the salience of relatively small gaps in remuneration. We therefore expected workers to report injustice and demotivation regarding relative remuneration, despite the closing of remuneration gaps between expatriate and local workers due to the economic development of recent years. To explore that possibility, 482 skilled professionals from a variety of sectors and organizations in two emerging economies, India (n = 233, response rate = 54%) and China (n = 249, response rate = 58%), participated in the research. International salaries were greater than local salaries by a factor of 2.73:1 in India and 1.90:1 in China; these mean ratios bordered on intolerable in the India sample and were largely tolerable among the sample from China. In both countries, differently remunerated workers differed in their justice cognitions and their demotivation, with lowered motivation and fewer justice cognitions in the locally salaried, local workers. These differences were however more statistically significant between people working in India than in China. Insofar as the motivational and justice gaps persisted, the findings support relative deprivation theory. Insofar as the same gaps appear to be sharper in the country with the higher-not lower-mean remuneration differential, they do not. An in country workshop with local experts who interpreted the findings (in India), and content analysis of the participants' recommendations (in China) jointly recommended linking remuneration to (i) workplace performance instead of (ii) economy-of-origin, to help promote (iii) fairness. PMID- 22044058 TI - Can professions contribute to the reduction of world-wide poverty?: a case in point: organizational psychology and pay diversity. PMID- 22044059 TI - Decent work and decent pay: dual salary systems and poverty reduction policy. PMID- 22044060 TI - An exploratory assessment of cultural sensitivity in the practices of Lebanese researchers in the field of psychology: implications for national development efforts. AB - The inclusion of the social and cultural characteristics of groups in the concept of national development highlights the contributions that culturally sensitive psychological research can make to development efforts. It also highlights the relevance of assessing and promoting such research, especially in majority world countries where development needs are pressing. In the current study, a content analysis was conducted to assess the degree to which Lebanese psychological researchers in post-civil war Lebanon have engaged in culturally sensitive research practices. The Cultural Sensitivity Measure for Published Research, which was inspired by Adair, Puhan, and Vohra's ( 1993 ) measure of indigenization, was applied to 54 peer-reviewed English- and French-language empirical studies conducted by Lebanese researchers on Lebanese samples within Lebanon. The results suggest that while cultural sensitivity levels were generally low, the sampled researchers engaged in more sensitive practices compared to researchers in the region. For example, they used qualitative methods more often, made more efforts to ensure the cultural compatibility of their methods, and engaged in more complex conceptualizations of culture and its relationship with psychological processes. Furthermore, certain practices, such as studying diverse groups or using findings to suggest real-life applications, were found to be predictive of higher general levels of cultural sensitivity in the sampled articles. These research practices could be fostered in institutional and intellectual contexts, and such initiatives would go a long way in supporting a locally appropriate research infrastructure that contributes to national development efforts. PMID- 22044061 TI - No need to fake it: reproduction of the Asch experiment without confederates. AB - In the present experiment, we replicated Asch's seminal study on social conformity without using confederates. We adapted a presentation trick in order to present two different stimuli secretly to groups of participants to create minorities and majorities without utilizing confederates. One hundred and four Japanese undergraduates (40 men and 64 women) carried out Asch-equivalent tasks in same-sex groups of four. In each group, we adapted the fMORI Technique to present the tasks such that one person (minority participant) observed different stimuli than the other three people (majority participants). The same nine stimulus sets that Asch had used were carefully reproduced as PowerPoint slides and projected onto a half-transparent screen. As for the critical tasks, the top part of the standard lines appeared in either green or magenta so that two groups of participants would see them differently when they wore two types of polarizing sunglasses that filtered either green or magenta to make the lines appear longer or shorter. A post-experimental questionnaire confirmed that no participant among either the minority or majority viewers noticed the presentation trick. The results showed that, in line with Asch's basic findings, the minority women participants conformed to the majority. However, our study produced two different results: While minority women conformed, minority men did not. Contrary to Asch's findings, the frequency of conformity of minority participants was almost the same regardless of whether the majority answered unanimously or not. PMID- 22044062 TI - Annual Report of the International Union of Psychological Science (IUPsyS). PMID- 22044063 TI - Latex of Euphorbia antiquorum induces apoptosis in human cervical cancer cells via c-jun n-terminal kinase activation and reactive oxygen species production. AB - Latex of Euphorbia antiquorum (EA) has inhibitory effects on several different cancer cell lines. However, the molecular mechanism of EA inhibitory effects on human cervical cancer HeLa cell growth has not been explored. EA induced apoptosis, which was characterized by morphological change, DNA fragmentation, increased sub-G1 population, and alterations in levels of apoptosis-associated proteins. Treatment with EA increased cell death and expression levels of caspase 8, -9, and -3. EA suppressed expression of Bcl-2, increased Bax, and reduced cleavage of Bid and the translocation of tBid to the mitochondria and the release of cytochrome c from mitochondria. EA caused a loss of mitochondrial membrane potential (DeltaPsim) and an increase in cellular reactive oxygen species (ROS). EA-induced ROS formation was suppressed by cyclosporine A (an inhibitor of the DeltaPsim) or allopurinol (an effective scavenger of ROS). EA also increased expression of Fas, FasL, and c-Jun N-terminal kinase (JNK), p38, and mitogen activated protein kinase (MAPK) and decreased expression of extracellular signal regulated kinase (ERK) 1/2-p. Co-treatment with the JNK inhibitor SP600125 inhibited EA-induced apoptosis and the activation of caspase-8, -9, and -3. Results of this study provide support for the hypothesis that EA causes cell death via apoptotic pathways in human cervical adenocarcinoma HeLa cells. PMID- 22044064 TI - Separating the air quality impact of a major highway and nearby sources by nonparametric trajectory analysis. AB - Nonparametric Trajectory Analysis (NTA), a receptor-oriented model, was used to assess the impact of local sources of air pollution at monitoring sites located adjacent to highway I-15 in Las Vegas, NV. Measurements of black carbon, carbon monoxide, nitrogen oxides, and sulfur dioxide concentrations were collected from December 2008 to December 2009. The purpose of the study was to determine the impact of the highway at three downwind monitoring stations using an upwind station to measure background concentrations. NTA was used to precisely determine the contribution of the highway to the average concentrations measured at the monitoring stations accounting for the spatially heterogeneous contributions of other local urban sources. NTA uses short time average concentrations, 5 min in this case, and constructed local back-trajectories from similarly short time average wind speed and direction to locate and quantify contributions from local source regions. Averaged over an entire year, the decrease of concentrations with distance from the highway was found to be consistent with previous studies. For this study, the NTA model is shown to be a reliable approach to quantify the impact of the highway on local air quality in an urban area with other local sources. PMID- 22044066 TI - Real-time NMR studies of electrochemical double-layer capacitors. AB - (11)B NMR spectroscopy has been used to investigate the sorption of BF(4)(-) anions on a highly porous, high surface area carbon, and different binding sites have been identified. By implementing in situ NMR approaches, the migration of ions between the electrodes of the supercapacitors and changes in the nature of ion binding to the surface have been observed in real time. PMID- 22044065 TI - Markers of inflammation in midlife women with intimate partner violence histories. AB - BACKGROUND: Lifetime occurrence of intimate partner violence (IPV) in women has been associated with increased prevalence of aging-related chronic diseases, including those with a pathophysiology involving inflammation. To begin to identify potential biologic mediators of this relationship, this cross-sectional study examined associations between past IPV and circulating levels of C-reactive protein (CRP) and interleukin-6 (IL-6)-measures linked with emergence of aging related diseases-along with in vitro IL-6 production by peripheral blood mononuclear cells (PBMC) stimulated with either phytohemagglutinin A (PHA) or lipopolysaccharide (LPS). METHODS: Apparently healthy, midlife women with divorce histories were recruited from the community. Histories of intimate partner psychological aggression, physical assault, sexual coercion, and stalking were assessed, along with current depression, posttraumatic stress symptoms, and health-related characteristics. At two visits, blood was drawn for assessment of biologic measures; measures were averaged across visits. RESULTS: In this sample (n=68), a history of being stalked was significantly positively correlated with CRP levels; in a multiple regression analysis that included body mass index (BMI) and current symptoms, this association was attenuated by adjusting for BMI. Physical assault history was significantly negatively correlated with PHA stimulated IL-6 production. This was most apparent for severe assault and was not accounted for by BMI or symptoms. CONCLUSIONS: IPV histories remitted for an average of 10 years were associated with biologic mediators of inflammation. The profile was not uniformly proinflammatory, suggesting that in situations of traumatic or chronic stress, different aspects of the inflammatory response are differentially regulated and subjected to diverse compensatory mechanisms. PMID- 22044068 TI - Tuning the molecular order of C60 functionalized phosphonic acid monolayers. AB - Mixed self-assembled monolayers (SAM) of alkyl phosphonic acids and C(60) functionalized octadecyl phosphonic acids (C(60)C(18)-PA) are deposited on alumina substrates from solution and are shown to form well-ordered structures with an insulating layer of alkyl chains and a semiconducting layer that comprises mainly C(60). Such an ordered structure is a necessity for the application of SAMs in organic transistors but is difficult to obtain since C(60)C(18)-PA without additional support do self-assemble in dense packaging but not in a well-ordered fashion. To avoid disordering of the SAM and to gain a better control of the interfacial properties we have investigated the stabilizing effects of fluorinated dodecyl phosphonic acids (FC(12)-PA) on the C(60)C(18)-PA monolayer. Vibrational sum-frequency (SFG) spectroscopy, ellipsometry, X-ray photoelectron spectroscopy, and electrical measurements were applied to study the mixed monolayers. Here, we make use of the differently labeled PA to determine surface coverages and molecular properties of the two species independently. Adsorption of FC(12)-PA gives rise to vibrational bands at 1344 cm(-1) and 1376 cm(-1) in SFG spectra, while a pronounced vibrational band centered at 1465 cm( 1) is attributable to C(60) vibrations. The coexistence of the bands is indicative for the presence of a mixed monolayer that is composed of both molecular species. Furthermore, a pronounced maximum in SFG intensity of the C(60) band is observed for SAMs, which are deposited from solutions with ~75% C(60)C(18)-PA and ~25% FC(12)-PA. The intensity maximum originates from successful stabilization of C(60) modified C(60)C(18)-PA by FC(12)-PA and a significantly improved molecular order. Conclusions from SFG spectra are corroborated by electric measurements that show best performance at these concentrations. Our results provide new information on the morphology and composition of C(60) modified SAMs and establish a route to fabricate well defined layers for molecular scale organic electronics. PMID- 22044067 TI - CNL, a ricin B-like lectin from mushroom Clitocybe nebularis, induces maturation and activation of dendritic cells via the toll-like receptor 4 pathway. AB - A novel lectin, isolated from the basidiomycete mushroom Clitocybe nebularis and termed C. nebularis lectin (CNL), exhibits an immunostimulatory effect on the most potent antigen-presenting cells, the dendritic cells (DCs). Treatment of human monocyte-derived DCs with CNL in doses from 1 to 10 MUg/ml resulted in a dose-dependent induction of overall DC maturation characteristics. Exposure of DCs to CNL for 48 hr resulted in extensive up-regulation of co-stimulatory molecules CD80 and CD86, as well as of the maturation marker CD83 and HLA-DR molecules. Such CNL-matured DCs (CNL-DCs) were capable of inducing a T helper type 1-polarized response in naive CD4+ CD45RA+ T cells in 5-day allogeneic co cultures. The allostimulatory potential of CNL-DCs was significantly increased relative to untreated controls, as was their capacity to produce several pro inflammatory cytokines such as interleukin-6, interleukin-8 and tumour necrosis factor-alpha. By using a specific Toll-like receptor 4 (TLR4) signalling inhibitor, CLI-095, as well as Myd88 inhibitory peptide, we have shown that DC activation by CNL is completely dependent on the TLR4 activation pathway. Furthermore, activation of TLR4 by CNL was confirmed via TLR4 reporter assay. Measurement of p65 nuclear factor-kappaB and p38 mitogen-activated protein kinase (MAPK) phosphorylation levels following CNL stimulation of DCs revealed primarily an increase in nuclear factor-kappaB activity, with less effect on the induction of p38 MAPK signalling than of lipopolysaccharide-matured DCs. The CNL had the ability to activate human DCs in such a way as to subsequently direct T helper type 1 T-cell responses. Our results encourage the use of mushroom-derived lectins for use in therapeutic strategies with aims such as to strengthen anti tumour immune responses. PMID- 22044069 TI - Laparoscopic bilateral oophorectomy - feasible migraine management? PMID- 22044070 TI - A comparison of immunogenicity of norovirus GII-4 virus-like particles and P particles. AB - Norovirus (NoV) -derived virus-like particles (VLPs) resemble empty shells of the virus and NoV P-particles contain only protruding domains of the NoV capsid. Both NoV-derived subviral particles show similar functionality and antigenicity in vitro and are considered to be potential vaccine candidates against NoV gastroenteritis. BALB/c mice were immunized with baculovirus-produced GII-4 VLPs or the corresponding Escherichia coli-produced P-particles by the intramuscular or intradermal route and the NoV-specific antibody and T-cell immune responses were compared. Elevated antibody levels were induced with a single VLP immunization, whereas P-particle immunization required a boost. High avidity antibodies were raised only by VLP immunization. VLP immunization resulted in a balanced T helper type 1/type 2 immune response whereas P-particles induced a T helper type 2-biased response. Only VLP immunization primed T cells for interferon-gamma production. Most importantly, cross-reactive B and T cells were induced solely by VLP immunization. In addition, VLP antiserum blocked the binding of heterotypic VLPs to human histo-blood group antigen receptor and saliva. The findings in this study are relevant for the development of NoV vaccines. PMID- 22044071 TI - Search for variation in the ovine KAP7-1 and KAP8-1 genes using polymerase chain reaction-single-stranded conformational polymorphism screening. AB - Keratins and keratin-associated proteins (KAPs) are large heterogeneous groups of proteins that constitute about 90% of the wool fiber. The genes encoding the high glycine-tyrosine (HGT) KAPs are the first sub-group of KAP genes expressed in the wool follicle and just after expression of the keratin genes. Little is known about variation in these genes, which led us to investigate two HGT-KAP genes, KRTAP7-1 and KRTAP8-1. Polymerase chain reaction-single-stranded conformational polymorphism analysis was used to investigate these genes in 250 Romney-cross sheep. For KRTAP7-1, two unique banding patterns were detected for amplicons that spanned the entire coding region. Sequencing confirmed the presence of two sequences with only one nucleotide difference (c.173G/A) putatively resulting in p.Ser58Asn. One was identical to the published ovine KRTAP7-1 sequence. For KRTAP8-1, five unique banding patterns were detected in an amplicon that spanned the entire coding region. Sequencing revealed five different DNA sequences, all of which were highly homologous to the previously reported ovine KRTAP8-1 sequence. Among these five sequences, four single-nucleotide substitutions were identified and three of them were located in the coding region. One of these was nonsynonymous and would putatively result in p.Tyr34Asn. The variation detected in KRTAP7-1 and KRTAP8-1 may influence their expression or protein structure. PMID- 22044072 TI - Estimating the origin and evolution characteristics for Korean HIV type 1 subtype B using Bayesian phylogenetic analysis. AB - The majority of Korean human immunodeficiency virus type 1 (HIV-1) isolates are composed of the Korean clade B strain that is distinct from the subtype B prevalent in North America and Europe. However, it is still not clear how HIV-1 was introduced, transmitted, and evolved within the Korean population. To identify the evolutionary characteristics of Korean HIV-1, we estimate the molecular epidemic history of HIV-1 subtype B gp120 env in Korea in comparison with sequences isolated from other geographic locations. A Bayesian Markov chain Monte Carlo (MCMC) statistical inference was used to estimate the time of divergence of subtype B. The estimated time of divergence of subtype B and the distinct monophyletic Korean B cluster was estimated to be in the early and mid 1960s, respectively. Substitution rates were estimated at 7.3*10(-3) and 8.0*10( 3) substitutions per site per year for HIV-1 subtype B and Korean clade B, respectively. The demographic dynamics of two Korean data sets showed that the effective number of infections in Korea increased rapidly until the early 1980s, and then the rate only slowly increased until the mid-1990s when the population growth approached a steady-state. These results suggest that the growth rate of prevalent HIV-1 strains in Korea was lower than in other countries, suggesting that the evolution of HIV-1 Korean clade B was relatively slow. Furthermore, the limited transmission of HIV-1 within the Korean population likely led to the independent evolution of this virus to form the HIV-1 Korean clade B. PMID- 22044073 TI - Simultaneous analysis of heparan sulfate, chondroitin/dermatan sulfates, and hyaluronan disaccharides by glycoblotting-assisted sample preparation followed by single-step zwitter-ionic-hydrophilic interaction chromatography. AB - Glycosaminoglycans (GAGs) play important roles in cell adhesion and growth, maintenance of extracellular matrix (ECM) integrity, and signal transduction. To fully understand the biological functions of GAGs, there is a growing need for sensitive, rapid, and quantitative analysis of GAGs. The present work describes a novel analytical technique that enables high throughput cellular/tissue glycosaminoglycomics for all three families of uronic acid-containing GAGs, hyaluronan (HA), chondroitin sulfate (CS)/dermatan sulfate (DS), and heparan sulfate (HS). A one-pot purification and labeling procedure for GAG Delta disaccharides was established by chemo-selective ligation of disaccharides onto high density hydrazide beads (glycoblotting) and subsequent labeling by fluorescence. The 17 most common disaccharides (eight comprising HS, eight CS/DS, and one comprising HA) could be separated with a single chromatography for the first time by employing a zwitter-ionic type of hydrophilic-interaction chromatography column. These novel analytical techniques were able to precisely characterize the glycosaminoglycome in various cell types including embryonal carcinoma cells and ocular epithelial tissues (cornea, conjunctiva, and limbus). PMID- 22044074 TI - Generation of reactive oxygen species mediated by humic-like substances in atmospheric aerosols. AB - Particulate matter (PM)-mediated reactive oxygen species (ROS) generation has been implicated in health effects posed by PM. Humic-like substances (HULIS) are an unresolved mixture of water-extracted organic compounds from atmospheric aerosol particles or isolated from fog/cloudwater samples. In this study, we use a cell-free dithiothreitol (DTT) assay to measure ROS production mediated by HULIS. The HULIS samples are isolated from aerosols collected at a rural location and a suburban location in the Pearl River Delta, China. In our experiments, ROS activities by residue metal ions in the HULIS fraction are suppressed by including a strong chelating agent in the DTT assay. Under conditions of DTT consumption not exceeding 90%, the HULIS-catalyzed oxidation of DTT follows the zero-order kinetics with respect to DTT concentration, and the rate of DTT oxidation is proportional to the dose of HULIS. The ROS activity of the aerosol HULIS, on a per unit mass basis is 2% of the ROS activity by a reference quinone compound, 1,4-naphthoquinone and exceeds that of two aquatic fulvic acids. The HULIS fraction in the ambient samples tested exhibits comparable ROS activities to the organic solvent extractable fraction, which would contain compounds such as quinones, a known organic compound class capable of catalyzing generation of ROS in cells. HULIS was found to be the major redox active constituent of the water-extractable organic fraction in PM. It is plausible that HULIS contains reversible redox sites, thereby serving as electron carriers to catalyze the formation of ROS. Our work suggests that HULIS could be an active PM component in generating ROS and further work is warranted to characterize its redox properties. PMID- 22044076 TI - Metagenome-based screening reveals worldwide distribution of LOV-domain proteins. AB - Metagenomes from various environments were screened for sequences homologous to light, oxygen, voltage (LOV)-domain proteins. LOV domains are flavin binding, blue-light (BL)-sensitive photoreceptors present in 10-15% of deposited prokaryotic genomes. The LOV domain has been selected, since BL is an ever present and sometimes harmful environmental factor for microbial communities. The majority of the metagenome material originated from the Sargasso Sea Project and from open-ocean sampling. In total, more than 40 million open reading frames were investigated for LOV-domain sequences. Most sequences were identified from aquatic material, but they were also found in metagenomes from soil and extreme environments, e.g. hypersaline ponds, acidic mine drainage or wastewater treatment facilities. A total of 578 LOV domains was assigned by three criteria: (1) the highly conserved core region, (2) the presence of minimally 14 essential amino acids and (3) a minimal length of 80 amino acids. More than three quarters of these identified genes showed a sequence divergence of more than 20% from database-deposited LOV domains from known organisms, indicating the large variation of this photoreceptor motif. The broad occurrence of LOV domains in metagenomes emphasizes their important physiological role for light-induced signal transduction, stress adaptation and survival mechanisms. PMID- 22044077 TI - Intranasal oxytocin and salivary cortisol concentrations during social rejection in university students. AB - Oxytocin facilitates pro-social behaviour and is proposed as a regulatory factor controlling stress reactivity. Previous research on oxytocin and stress has focused on achievement-related stressors among male participants. The aims of the study were to (1) examine the influence of oxytocin on the affective and cortisol response to the Yale Interpersonal Stressor (YIPS), a live social rejection paradigm, and (2) to replicate the finding that women exhibit a greater cortisol response to interpersonal stress than men (Stroud et al. 2002). Sex differences in stress responses: Social rejection versus achievement stress. Biol Psychiat 53:318-327. Ninety-six undergraduate students underwent the YIPS, where participants were excluded from two separate conversations by two same-sex confederates. Salivary cortisol concentrations and mood were repeatedly measured throughout the study. Participants were administered, in a double-blind design, a single dose of intranasal oxytocin (24 IU) or placebo prior to beginning the YIPS. The YIPS elicited a significant negative mood response that was more pronounced in females than in males. However, no significant cortisol response to the stressor and no sex difference in cortisol reactivity were observed. A significant effect of drug condition on cortisol levels was observed. Participants who were administered oxytocin exhibited a decrease in cortisol levels, relative to placebo, during the YIPS, F (4, 184)=4.50, p<0.05. The study failed to replicate the sex difference in the cortisol response to interpersonal stress reported by Stroud et al. (2002). Intranasal oxytocin, however, appeared to reduce cortisol concentrations during an interpersonal challenge. PMID- 22044078 TI - Health-related quality of life in patients with atopic dermatitis. AB - Atopic dermatitis (AD) is a chronic relapsing condition that can have considerable effects on the patients' quality of life (QOL). The aim of this study was to measure the health-related QOL in patients with AD, using generic and specific instruments, to compare the scores obtained by different instruments and to verify the relationship between them. We conducted a cross-sectional study of 132 outpatients with AD. To assess the QOL, Short Form 36 (SF-36), Dermatology Life Quality Index (DLQI) and Children's Dermatology Life Quality Index (CDLQI) were administered. In order to assess the disease severity of AD, we used the Eczema Area and Severity Index (EASI) and physician assessment of disease severity. Stressful life events during the last 12 months were assessed with Paykel's Interview for Recent Life Events. Patients with AD had inferior social functioning and mental health scores compared with the general population. The correlations between the DLQI and SF-36 were found for the mental components of the QOL. Increasing disease severity was associated with greater impairment in QOL in both, children and adults. Our study found the influence of the stressful life events on the role emotional of AD patients. These results demonstrate that AD influences health-related QOL, especially in children. This study supports the decision to use both generic and skin-specific instruments to assess the impact of AD on QOL. PMID- 22044079 TI - Self-report versus ultrasound measurement of uterine fibroid status. AB - BACKGROUND: Much of the epidemiologic research on risk factors for fibroids, the leading indication for hysterectomy, relies on self-reported outcome. Self-report is subject to misclassification because many women with fibroids are undiagnosed. The purpose of this analysis was to quantify the extent of misclassification and identify associated factors. METHODS: Self-reported fibroid status was compared to ultrasound screening from 2046 women in Right From The Start (RFTS) and 869 women in the Uterine Fibroid Study (UFS). Log-binomial regression was used to estimate sensitivity (Se) and specificity (Sp) and examine differences by ethnicity, age, education, body mass index, parity, and miscarriage history. RESULTS: Overall sensitivity was <=0.50. Sensitivity was higher in blacks than whites (RFTS: 0.34 vs. 0.23; UFS: 0.58 vs. 0.32) and increased with age. Parous women had higher sensitivity than nulliparae, especially in RFTS whites (Se ratio=2.90; 95% confidence interval [CI]: 1.51, 5.60). Specificity was 0.98 in RFTS and 0.86 in UFS. Modest ethnic differences were seen in UFS (Sp ratio, black vs. white=0.90; 95% CI: 0.81, 0.99). Parity was inversely associated with specificity, especially among UFS black women (Sp ratio=0.84; 95% CI: 0.73, 0.97). Among women who reported a previous diagnosis, a shorter time interval between diagnosis and ultrasound was associated with increased agreement between the two measures. CONCLUSIONS: Misclassification of fibroid status can differ by factors of etiologic interest. These findings are useful for assessing (and correcting) bias in studies using self-reported clinical diagnosis as the outcome measure. PMID- 22044080 TI - Occupational safety management: the role of causal attribution. AB - The paper addresses the causal attribution theory, an old and well-established theme in social psychology which denotes the everyday, commonsense explanations that people use to explain events and the world around them. The attribution paradigm is considered one of the most appropriate analytical tools for exploratory and descriptive studies in social psychology and organizational literature. It affords the possibility of describing accident processes as objectively as possible and with as much detail as possible. Causal explanations are vital to the formal analysis of workplace hazards and accidents, as they determine how organizations act to prevent accident recurrence. Accordingly, they are regarded as fundamental and prerequisite elements for safety management policies. The paper focuses primarily on the role of causal attributions in occupational and industrial accident analyses and implementation of safety interventions. It thus serves as a review of the contribution of attribution theory to occupational and industrial accidents. It comprises six sections. The first section presents an introduction to the classic attribution theories, and the second an account of the various ways in which the attribution paradigm has been applied in organizational settings. The third and fourth sections review the literature on causal attributions and demographic and organizational variables respectively. The sources of attributional biases in social psychology and how they manifest and are identified in the causal explanations for industrial and occupational accidents are treated in the fifth section. Finally, conclusion and recommendations are presented. The recommendations are particularly important for the reduction of workplace accidents and associated costs. The paper touches on the need for unbiased causal analyses, belief in the preventability of accidents, and the imperative role of management in occupational safety management. PMID- 22044081 TI - Accents in the workplace: their effects during a job interview. AB - As the workplace becomes increasingly global, organizations are more likely to employ persons from other countries whose accents clearly identify them as different from the local workforce. Understanding the impact of accents in the workplace is important because accents can be salient in the same way as ethnicity, age, gender, and skin color and may be a source of employment discrimination. The present study looked at the influence of accents on the evaluation of job applicants during an interview for a human resource manager position. Participants from the US were asked to evaluate an applicant with one of three accents (Midwestern US, French, Colombian) by listening to an audiofile. The results showed that the applicant with the Midwestern US accent was evaluated more positively than the applicant with the French accent; however, the applicant with the Colombian accent did not receive an evaluation that differed significantly from those given to the applicants with either the French or the Midwestern US accent. Analyses of process variables indicated that the bias against the French-accented applicant was mediated by perceived lower similarity. These results are consistent with the similarity-attraction hypothesis, which states that demographic variables will impact judgments to the extent to which they make the decision-maker view the applicant as similar or dissimilar. The ability of accent to trigger bias highlights the importance of considering the full array of characteristics that can lead to discrimination in employment settings. Research on employment discrimination has traditionally focused on visual cues such as gender and ethnicity, but in an interview situation, the way the applicant speaks is also important. PMID- 22044082 TI - Perfectionism, anger, and anger rumination. AB - Anger and anger rumination are considered to be detrimental to both physical and psychological well being. Furthermore, perfectionism, as a personality construct, seems to be related to various types of maladjustment. Whereas perfectionism has been characterized as being positive when an individual derives pleasure from striving for excellence yet recognizes and accepts individual limitations, it is deemed negative when the individual has unrealistic expectations and is never satisfied with his or her performance. The present study examined whether positive and negative perfectionism was associated with anger and anger rumination. The Farsi version of the Positive and Negative Perfectionism Scale and the Farsi version of the Anger Rumination Scale, as well as Spielberger's State-Trait Anger Scale were completed by 384 Iranian students. Results showed that anger and anger rumination were, as expected, associated negatively with positive perfectionism and associated positively with negative perfectionism. Positive perfectionism enables individuals to strive for success in a flexible manner and, thus, to experience satisfaction and pleasure rather than dissatisfaction, frustration, and anger. Conversely, negative perfectionism makes individuals vulnerable to emotional distress such as predisposition to experience anger and anger rumination through setting high standards for performance, overgeneralization of perceived failures, negative self-evaluation, self-blame, and measuring self-worth in terms of unachievable goals of accomplishment and productivity. Hence, perfectionism may be regarded as having both adaptive and maladaptive aspects with regard to health. PMID- 22044083 TI - The emergence, structure and development of ethnic identity during childhood: the case of Roma identity. AB - This study investigates the emergence, development and structure of ethnic identity during childhood. Forty Roma children living in Greece aged between 2.8 and 11.9 years answered questions about their awareness/recognition of four aspects of their ethnic identity-namely place of habitation, traditional costumes, the Roma language, and early betrothal of children-their identity and their sense of stability and constancy. The study also investigates how the children feel about the abandonment of those four aspects. The evidence from the current data supports the hypothesis that awareness of ethnic identity emerges before the age of 4. Moreover, this study offers direct empirical evidence of the multidimensionality of ethnic identity. A model of three concentric rings is proposed, extending from a core containing the most highly valued aspects of ethnic identity to the outer annulus that comprises the nonpermanent and nonstable aspects of ethnic identity. The aspects in each annulus differ in terms of the development of the sense of stability and constancy and the feelings associated with loss of the aspects in question. Even the youngest participants considered the aspects in the core to be stable and constant as well as emotionally charged; and even the 11-year-olds did not consider the aspects contained in the outer, more fluid annulus as stable and constant aspects of their ethnic identity. The development of an aspect is determined by what the majority of adults in a society, at a particular time in history, consider to be most important. PMID- 22044084 TI - Visual rapid naming and phonological abilities: different subtypes in dyslexic children. AB - One implication of the double-deficit hypothesis for dyslexia is that there should be subtypes of dyslexic readers that exhibit rapid naming deficits with or without concomitant phonological processing problems. In the current study, we investigated the validity of this hypothesis for Portuguese orthography, which is more consistent than English orthography, by exploring different cognitive profiles in a sample of dyslexic children. In particular, we were interested in identifying readers characterized by a pure rapid automatized naming deficit. We also examined whether rapid naming and phonological awareness independently account for individual differences in reading performance. We characterized the performance of dyslexic readers and a control group of normal readers matched for age on reading, visual rapid naming and phonological processing tasks. Our results suggest that there is a subgroup of dyslexic readers with intact phonological processing capacity (in terms of both accuracy and speed measures) but poor rapid naming skills. We also provide evidence for an independent association between rapid naming and reading competence in the dyslexic sample, when the effect of phonological skills was controlled. Altogether, the results are more consistent with the view that rapid naming problems in dyslexia represent a second core deficit rather than an exclusive phonological explanation for the rapid naming deficits. Furthermore, additional non-phonological processes, which subserve rapid naming performance, contribute independently to reading development. PMID- 22044085 TI - Body dissatisfaction, maternal appraisal, and depressive symptoms in Hong Kong adolescents. AB - Body dissatisfaction, its risk factors and association with depressed mood have been well investigated in the West. However, more studies are needed to examine further the relation between body dissatisfaction and depressive symptoms and the factors influencing body dissatisfaction in non-Western cultures. The present study examined in a sample of Hong Kong Chinese adolescents the relation between body dissatisfaction and depressive symptoms, and the relation of maternal appraisal of their adolescent's figure to the adolescent's body dissatisfaction and depressive symptoms. We obtained information from 379 boys and 254 girls about their body dissatisfaction and depressive symptoms. Their mothers provided information about their appraisal of their adolescent's body shape and size compared to ideal. Body dissatisfaction was related to depressive symptoms in girls (B = 2.58, p <.01), but not in boys (B = -0.08, p >.10). Negative maternal appraisal did not have direct effects on adolescents' depressive symptoms (B = 0.14, p =.75), but the association between negative maternal appraisal and body dissatisfaction was significantly stronger in adolescents whose ideal was smaller than they perceived themselves to be (B = 0.32, p <.01) than those whose ideal was larger than their own perception (B = 0.14, p < .01). Our findings suggest that maternal appraisal had indirect effects on mood, acting through adolescents' body dissatisfaction, and that body dissatisfaction may be a sex-specific risk factor for depression. This study points to the need for testing and adapting programs to reduce body dissatisfaction particularly in girls at risk for depression, and to raise mothers' awareness of the link between their negative appraisals and their adolescents' body dissatisfaction and depressive symptoms. PMID- 22044086 TI - Belief in a just world and subjective well-being: mothers of normal and Down syndrome children. AB - A cross-sectional study examined the relationship between three dimensions of the belief in a just world and the subjective well-being of Pakistani mothers of normal and Down syndrome children (n = 100 each). Personal belief in a just world and two dimensions of general belief in a just world-beliefs in immanent and ultimate justice-were assessed along with four dimensions of subjective well being: life satisfaction, mood, state anxiety, and depression. It was hypothesized that personal belief in a just world and belief in ultimate justice would be positively associated with subjective well-being for both groups of mothers. Results were obtained through moderated regression analyses. In line with our hypothesis, personal belief in a just world positively predicted life satisfaction and mood level and negatively predicted state anxiety and depression in both groups of mothers. In contrast, beliefs in immanent and ultimate justice were not consistently adaptive. In particular, the more the mothers of a Down syndrome child believed in immanent justice, the more anxiety they experienced the previous week. In addition, the more the mothers of normal children believed in ultimate justice, the more they experienced anxiety. The pattern of results persisted when controlled for mothers' education, the total number of their children and marital status. Overall, the results support the role of personal belief in a just world as a personal resource in adverse as well as normal life circumstances. PMID- 22044087 TI - The association between reality-based beliefs and indirectly experienced traumatization. AB - The purpose of the study was to examine the association between belief types and the magnitude of indirect traumatization. Specific types of beliefs were defined in terms of the cognitive orientation theory, which is a cognitive-motivational approach to the understanding, predicting, and changing of behaviors. Belief types that were analyzed included beliefs about self, general beliefs, beliefs about norms, and goal beliefs as they relate to personal growth. Study participants included 38 rescuers (body handlers), 37 nurses, and 31 rehabilitation workers who treated injured civilians that had been exposed to politically motivated violence. The Cognitive Orientation for Posttraumatic Growth Scale was used to assess beliefs about personal growth. The Revised Posttraumatic Stress Disorder Inventory was administered to evaluate indirect traumatization. The results indicate that three of the four belief types related to personal growth were associated with the level of indirect traumatization. Optimistic and positive beliefs about self and general beliefs were associated with a lower level of indirect traumatization symptomatology, suggesting that these types of beliefs may counteract indirect traumatization. On the other hand, stronger goal beliefs were associated with greater indirect traumatization. The negative association between positive goal beliefs and indirect trauma may be related to the gap the individual perceives between the hoped-for ideals and the trauma-stricken reality. These results indicate the importance of cognitive beliefs and their possible role in determining the response to indirect traumatization. PMID- 22044089 TI - Long-term outcome in patients with juvenile dermatomyositis: a cross-sectional follow-up study. AB - OBJECTIVE: To evaluate a group of 53 patients with juvenile dermatomyositis (JDM), on average 13.9 years after disease onset, in order to describe the long term disease outcome and to identify disease-related parameters associated with poor disease outcome. METHODS: Baseline information at disease onset was obtained from medical records. Disease status at follow-up was evaluated by physical examination. The Myositis Damage Index (MDI) and the Myositis Disease Damage by Visual Analogue Scale (MYODAM-VAS) were used to describe disease damage. RESULTS: Disease damage was seen in 60.4% of patients. The most common damage was cutaneous scarring (39.6%) and muscle dysfunction (34%). Calcinosis was found in 20%, lipodystrophy in 13%, and severe damage affecting more than two organ systems in 24.5% of patients. A disease duration > 4 years increased the risk of damage based on: MDI score [adjusted odds ratio (AOR) 8.3, 95% confidence interval (CI) 1.7-41.7], MYODAM-VAS score (AOR 26.2, 95% CI 3.1-223.7), and number of affected organs (AOR 16.3, 95% CI 1.1-232.4). Disease onset age >= 7.4 years increased the risk of more than two affected organs (AOR 15.8, 95% CI 1.9 129.4). Disease duration >= 4 years increased the risk of calcinosis (OR 4.8, 95% CI 1.1-20.9) and continuous muscle dysfunction (OR 4.2, 95% CI 1.1-17.3). CONCLUSION: In a long-term follow-up study, 60% of JDM patients had disease damage at a mean of 14 years after disease onset. Longer disease duration was the most important predictor of damage, calcinosis, and impaired muscle function, and higher age at disease onset predicted more organs involved at follow-up. PMID- 22044092 TI - Fighting blindness with adeno-associated virus serotype 8. PMID- 22044090 TI - Humoral immune responses in humanized BLT mice immunized with West Nile virus and HIV-1 envelope proteins are largely mediated via human CD5+ B cells. AB - BLT mice, constructed by surgical implantation of human fetal thymus-liver tissues and intravenous delivery of autologous CD34+ haematopoietic stem cells into adult non-obese diabetic/severe combined immunodeficiency mice, were evaluated for vaccine-induced humoral immune responses. Following engraftment, these mice developed a human lymphoid system; however, the majority of the peripheral human B lymphocytes displayed an immature phenotype as evidenced by surface CD10 expression. Over 50% of the human B cells in the periphery but not in the bone marrow also expressed the CD5 antigen, which is found only infrequently on mature follicular B cells in humans. A single intramuscular immunization with recombinant viral envelope antigens, e.g., HIVgp140 and West Nile Virus envelope proteins, together with the immune stimulatory KLK/ODN1a composition) [corrected] adjuvant resulted in seroconversion characterized by antigen-specific human antibodies predominantly of the IgM isotype. However, repeated booster immunizations did not induce secondary immune responses as evidenced by the lack of class switching and specific IgM levels remaining relatively unchanged. Interestingly, the peripheral CD19+ CD5+ but not the CD19+ CD5- human B lymphocytes displayed a late developing CD27+ IgM+ memory phenotype, suggesting that the CD5+ B-cell subset, previously implicated in 'natural antibody' production, may play a role in the vaccine-induced antibody response. Furthermore, human T lymphocytes from these mice demonstrated suboptimal proliferative responses and loss of co-stimulatory surface proteins ex vivo that could be partially reversed with human interleukin-2 and interleukin-7. Therefore, vaccine-induced immune responses in BLT mice resemble a T-cell independent pathway that can potentially be modulated in vivo by the exogenous delivery of human cytokines/growth factors. PMID- 22044093 TI - Progress and prospects: advancements in retroviral vector design, generation, and application. PMID- 22044094 TI - Adeno-associated viral vectors for hereditary emphysema; progressing along the clinical development highway. PMID- 22044095 TI - A new diphenyl ether from Phoma sp. strain, SHZK-2. AB - A new diphenyl ether methyl 2-(2-formyl-3-hydroxy-5-methylphenoxy)-5-hydroxy-3 methoxybenzoate (3), together with four known compounds, asterric acid (1), methyl asterrate (2), 9(Z),12(Z)-nonadecadienoic acid (4) and orsellinic acid (5), were isolated from the Phoma sp. strain SHZK-2, which was isolated from a polluted environment in southern China. The structures of these compounds were determined by spectroscopic methods. Cytotoxicities of compounds against HEPG2 cell and Raji cell lines were preliminarily evaluated by the MTT method. PMID- 22044097 TI - Vitamin D: one size does not fit all. PMID- 22044096 TI - Regulatory T cells play a role in T-cell receptor CDR2 peptide regulation of experimental autoimmune encephalomyelitis. AB - Eliciting T-cell receptor (TCR) -specific responsiveness has been known to provide an effective autoregulatory mechanism for limiting inflammation mediated by T effector cells. Our previous use of TCR peptides derived from the CDR3 regions of a pathogenic TCR effectively reversed ongoing experimental autoimmune encephalomyelitis (EAE) in a humanized TCR transgenic model. In this study, we use the TCR BV8S2 CDR2 peptide in the non-transgenic C57BL/6 EAE model to down regulate the heterogeneous TCR BV8S2(+) MOG-35-55-specific pathogenic T-cell population and demonstrate successful treatment of EAE after disease onset. Suppression of disease was associated with reduced MOG-35-55-specific and non specific T-cell production of interleukin-17a and interferon-gamma in the central nervous system, as well as reduced numbers of CD4(+) and Foxp3(+) T cells in the central nervous system. With the use of Foxp3-GFP and Foxp3 conditional knockout mice, we demonstrate that the TCR CDR2 peptide treatment effect is dependent on the presence of Foxp3(+) regulatory T cells and that regulatory T cell numbers are significantly expanded in the periphery of treated mice. Hence, TCR CDR2 peptide therapy is effective in regulating heterogeneous, pathogenic T cell populations through the activity of the Foxp3(+) regulatory T cell population. PMID- 22044098 TI - Mechanisms and consequences of head injuries in soccer: a study of 451 patients. AB - OBJECT: The goal of this study was to evaluate the incidence and mechanisms of head injury during soccer games and to describe the results after spontaneous resolution of symptoms or after treatment. METHODS: In a retrospective study from 2005, records on 451 players from the German Soccer Association who had suffered various injuries were collected. The study used a questionnaire in which the player described the accident and the playing situation as well as the clinical course after trauma. This questionnaire also included information about the physical symptoms of the players and the length of their rehabilitation. Two groups were formed: one with head injuries (case group), and the other with injuries of other body parts (control group). RESULTS: Of the injuries reported, 108 (23.9%) were related to the head, 114 (25.3%) to the knee, 58 (13%) to the ankle, 56 (12%) to the calf, and 30 (7%) to the shoulder. The areas of the head most frequently involved were the facial and occipital regions. In the head injury group, the head duel was the most common playing action to lead to trauma. In those cases, the body part that hit the injured player was the elbow, arm, or head of the opponent. The most common playing situation was combat in the penalty area. The median hospitalization time after the trauma was 2 days for the case group and 5 days for the control group. The rehabilitation time for the case group was also shorter (median 6.5 days) than for the control group (median 30 days). CONCLUSIONS: Trivial head injuries in soccer can have a long and complicated course. Nevertheless, the temporary disability is shorter in most cases than for players with injuries to other parts of the body. Modifying the rules of play would be necessary to reduce the incidence of head trauma. PMID- 22044099 TI - Axillary nerve injury associated with sports. AB - OBJECT: The aim of this retrospective study was to present and investigate axillary nerve injuries associated with sports. METHODS: This study retrospectively reviewed 26 axillary nerve injuries associated with sports between the years 1985 and 2010. Preoperative status of the axillary nerve was evaluated by using the Louisiana State University Health Science Center (LSUHSC) grading system published by the senior authors. Intraoperative nerve action potential recordings were performed to check nerve conduction and assess the possibility of resection. Neurolysis, suture, and nerve grafts were used for the surgical repair of the injured nerves. In 9 patients with partial loss of function and 3 with complete loss, neurolysis based on nerve action potential recordings was the primary treatment. Two patients with complete loss of function were treated with resection and suturing and 12 with resection and nerve grafting. The minimum follow-up period was 16 months (mean 20 months). RESULTS: The injuries were associated with the following sports: skiing (12 cases), football (5), rugby (2), baseball (2), ice hockey (2), soccer (1), weightlifting (1), and wrestling (1). Functional recovery was excellent. Neurolysis was performed in 9 cases, resulting in an average functional recovery of LSUHSC Grade 4.2. Recovery with graft repairs averaged LSUHSC Grade 3 or better in 11 of 12 cases CONCLUSIONS: Surgical repair can restore useful deltoid function in patients with sports-associated axillary nerve injuries, even in cases of severe stretch-contusion injury. PMID- 22044100 TI - Peroneal nerve injury associated with sports-related knee injury. AB - OBJECT: This study analyzes 84 cases of peroneal nerve injuries associated with sports-related knee injuries and their surgical outcome and management. METHODS: The authors retrospectively reviewed the cases of peroneal nerve injury associated with sports between the years 1970 and 2010. Each patient was evaluated for injury mechanism, preoperative neurological status, electrophysiological studies, lesion type, and operative technique (neurolysis and graft repair). Preoperative status of injury was evaluated by using a grading system published by the senior authors. All lesions in continuity had intraoperative nerve action potential recordings. RESULTS: Eighty-four (approximately 18%) of 448 cases of peroneal nerve injury were found to be sports related, which included skiing (42 cases), football (23 cases), soccer (8 cases), basketball (6 cases), ice hockey (2 cases), track (2 cases) and volleyball (1 case). Of these 84 cases, 48 were identified as not having fracture/dislocation and 36 cases were identified with fracture/dislocation for surgical interventions. Good functional outcomes from graft repair of graft length < 6 cm (70%) and neurolysis (85%) in low-intensity peroneal nerve injuries associated with sports were obtained. Recovery from graft repair of graft length between 6 and 12 cm (43%) was good and measured between Grades 3 and 4. However, recovery from graft repair of graft length between 13 and 24 cm was obtained in only 25% of patients. CONCLUSIONS: Traumatic knee-level peroneal nerve injury due to sports is usually associated with stretch/contusion, which more often requires graft repair. Graft length is the factor to be considered for the prognosis of nerve repair. PMID- 22044101 TI - Sports-related chronic repetitive head trauma as a cause of pituitary dysfunction. AB - Traumatic brain injury (TBI) is recognized as a cause of hypopituitarism even after mild TBI. Although over the past decade, a growing body of research has detailed neuroendocrine changes induced by TBI, the mechanisms and risk factors responsible for this pituitary dysfunction are still unclear. Around the world, sports-especially combative sports-are very popular. However, sports are not generally considered as a cause of TBI in most epidemiological studies, and the link between sports-related head trauma and hypopituitarism has not been investigated until recently. Thus, there is a paucity of data regarding this important concern. Because of the large number of young sports participants with near-normal life expectancy, the implications of undiagnosed or untreated postconcussion pituitary dysfunction can be dramatic. Understanding the pathophysiological mechanisms and risk factors of hypopituitarism caused by sports injuries is thus an important issue that concerns both medical staff and sponsors of sports. The aim of this paper was to summarize the best evidence for understanding the pathophysiological mechanisms and to discuss the current data and recommendations on sports-related head trauma as a cause of hypopituitarism. PMID- 22044102 TI - Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide. AB - Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries. PMID- 22044103 TI - Development of an iPhone application for sideline concussion testing. AB - Professional athletes are taking concussion very seriously, and missed play due to concussion is no longer stigmatized. One fortuitous consequence is increased awareness of the detrimental effects of concussion among student athletes. Whereas professional athletes have access to formal in-competition evaluation and out-of-competition monitoring programs, the majority of student athletes, especially at the middle school and high school levels, do not. The authors therefore set out to create an easy-to-use iPhone application for sideline concussion testing and serial monitoring of these at-risk athletes. PMID- 22044104 TI - Traumatic brain injury in pediatric patients: evidence for the effectiveness of decompressive surgery. AB - Traumatic brain injury (TBI) is the current leading cause of death in children over 1 year of age. Adequate management and care of pediatric patients is critical to ensure the best functional outcome in this population. In their controversial trial, Cooper et al. concluded that decompressive craniectomy following TBI did not improve clinical outcome of the analyzed adult population. While the study did not target pediatric populations, the results do raise important and timely clinical questions regarding the effectiveness of decompressive surgery in pediatric patients. There is still a paucity of evidence regarding the effectiveness of this therapy in a pediatric population, and there is an especially noticeable knowledge gap surrounding age-stratified interventions in pediatric trauma. The purposes of this review are to first explore the anatomical variations between pediatric and adult populations in the setting of TBI. Second, the authors assess how these differences between adult and pediatric populations could translate into differences in the impact of decompressive surgery following TBI. PMID- 22044105 TI - Definition and measurement of rider-intrinsic physical attributes influencing all terrain vehicle safety. AB - OBJECT: All-terrain vehicle (ATV) usage has grown tremendously over the years, reaching 9.5 million vehicles in use in 2007. Accompanying this growth has been a concomitant increase in rider morbidity (including traumatic brain and spine injuries) and death, especially in children. The purpose of this study was to define and measure, through field testing, those physical attributes intrinsic to riders, such as height, weight, and wingspan, which may have implications for ATV riders' safety. METHODS: Three field tests (J-hook, brake, and bump) were developed and performed to allow direct measurement of the lateral, longitudinal, and vertical dynamics in 5 riders of varying heights, weights, and wingspans. Two ATVs, a utility and a sport model, were tested for further comparisons. Data were acquired using a comprehensive data acquisition system attached to the ATVs. Assignment of individual rider/ATV test safety ratings and a rider/ATV Total Safety Rating were made from the results of these field tests. RESULTS: The J hook test results demonstrated that larger rider wingspans positively influence ATV rider safety and mitigate against lateral instability. From the brake test it was determined that a 10-in (25.4-cm) longitudinal displacement, such as that experienced during a sharp deceleration, for a rider of any height or weight, breached the level of defined safety. As rider weight increased, displacement decreased. The bump test provided evidence that increased rider weight also mitigates against vertical displacement. CONCLUSIONS: Individuals with light weights and small wingspans, such as those in the pediatric population, are under considerable risk of injury when operating an ATV due to lateral, longitudinal, and vertical operational instability. PMID- 22044106 TI - Cervical spinal stenosis and sports-related cervical cord neurapraxia. AB - Cervical cord neurapraxia is a common sports-related injury. It is defined as a transient neurological deficit following trauma localizing to the cervical spinal cord and can be caused by hyperextension, hyperflexion, or axial load mechanisms. Symptoms usually last less than 15 minutes, but can persist up to 48 hours in adults and as long as 5 days in children. While a strong causal relationship exists between cervical spine stenosis and cervical cord neurapraxia in adult patients, this association has not been observed in children. Likewise, while repeated episodes of neurapraxia can be commonplace in adult patients, recurrences have not been reported in the pediatric population. Treatment is usually supportive, but in adults with focal cervical lesions or instability, surgery is an option. Surgery for neurapraxia in children is rarely indicated. PMID- 22044107 TI - Spinal injury patterns among skiers and snowboarders. AB - OBJECT: Skiing and snowboarding injuries have increased with the popularity of these sports. Spinal cord injuries (SCIs) are a rare but serious event, and a major cause of morbidity and mortality for skiers and snowboarders. The purpose of this study is to characterize the patterns of SCI in skiers and snowboarders. METHODS: The authors queried the Nationwide Inpatient Sample for the years 2000 2008 for all patients admitted with skiing or snowboarding as the mechanism of injury, yielding a total of 8634 patients. The injury patterns were characterized by the ICD-9 diagnostic and procedure codes. The codes were searched for those pertaining to vertebral and skull fracture; spinal cord, chest, abdominal, pelvic, and vessel injuries; and fractures and dislocations of the upper and lower extremity. Statistical analysis was performed with ANOVA and Student t test. RESULTS: Patients were predominantly male (71%) skiers (61%), with the average age of the skiers being older than that of snowboarders (39.5 vs 23.5 years). The average length of stay for patients suffering from spine trauma was 3.8 days and was increased to 8.9 days in those with SCI. Among hospitalized patients, SCI was seen in 0.98% of individuals and was equally likely to occur in snowboarders and skiers (1.07% vs 0.93%, p < 0.509). Cervical spine trauma was associated with the highest likelihood of SCI (19.6% vs. 10.9% of thoracic and 6% of lumbar injuries, p < 0.0001). Patients who were injured skiing were more likely to sustain a cervical spine injury, whereas those injured snowboarding had higher frequencies of injury to the lumbar spine. The most common injury seen in tandem with spine injury was closed head injury, and it was seen in 13.4% of patients. Conversely, a spine injury was seen in 12.9% of patients with a head injury. Isolated spine fractures were seen in 4.6% of patients. CONCLUSIONS: Skiers and snowboarders evaluated at the hospital are equally likely to sustain spine injuries. Additionally, participants in both sports have an increased incidence of SCI with cervical spine trauma. PMID- 22044108 TI - Direct surgical repair of spondylolysis in athletes: indications, techniques, and outcomes. AB - OBJECT: Athletes present with back pain as a common symptom. Various sports involve repetitive hyperextension of the spine along with axial loading and appear to predispose athletes to the spinal pathology spondylolysis. Many athletes with acute back pain require nonsurgical treatment methods; however, persistent recurrent back pain may indicate degenerative disc disease or spondylolysis. Young athletes have a greater incidence of spondylolysis. Surgical solutions are many, and yet there are relatively few data in the literature on both the techniques and outcomes of spondylolytic repair in athletes. In this study, the authors undertook a review of the surgical techniques and outcomes in the treatment of symptomatic spondylolysis in athletes. METHODS: A systematic review of the MEDLINE and PubMed databases was performed using the following key words to identify articles published between 1950 and 2011: "spondylolysis," "pars fracture," "repair," "athlete," and/or "sport." Papers on both athletes and nonathletes were included in the review. Articles were read for data on methodology (retrospective vs prospective), type of treatment, number of patients, mean patient age, and mean follow-up. RESULTS: Eighteen articles were included in the review. Eighty-four athletes and 279 nonathletes with a mean age of 20 and 21 years, respectively, composed the population under review. Most of the fractures occurred at L-5 in both patient groups, specifically 96% and 92%, respectively. The average follow-up period was 26 months for athletes and 86 months for nonathletes. According to the modified Henderson criteria, 84% (71 of 84) of the athletes returned to their sports activities. The time intervals until their return ranged from 5 to 12 months. CONCLUSIONS: For a young athlete with a symptomatic pars defect, any of the described techniques of repair would probably produce acceptable results. An appropriate preoperative workup is important. The ideal candidate is younger than 20 years with minimal or no listhesis and no degenerative changes of the disc. Limited participation in sports can be expected from 5 to 12 months postoperatively. PMID- 22044109 TI - Sports-related neurosurgical injuries. PMID- 22044110 TI - Increased risk of multiple sclerosis after traumatic brain injury: a nationwide population-based study. AB - The etiology of multiple sclerosis (MS) is still not well known. Previous data show conflicting results regarding the association between MS and prior brain trauma. This study aims to investigate the risk for MS following a traumatic brain injury (TBI) using a large-scale cohort study design. This study used data from the National Health Insurance Research Database. A total of 72,765 patients with TBI were identified and included as the study cohort, and 218,295 randomly selected subjects were matched with the study cohort by sex and age as controls. We traced each patient individually for a 6-year period from their index health care utilization to identify those who received a subsequent diagnosis of MS. We used the Kaplan-Meier method and the log-rank test to compare the difference in 6 year MS-free survival rates between the two groups. Stratified Cox proportional hazard regressions were computed to compare the risk of developing MS for these two cohorts. Patients with TBI had a higher incidence of MS during the 6-year period than the comparison group (0.055% versus 0.037%). After excluding cases who died from non-MS causes, stratifying for hospitalization of cases as a proxy for severity, and adjusting for monthly income and geographic region of the community in which the patient resided, the hazard ratio (HR) of MS for patients with hospital-treated TBI injuries was 1.97 (95% CI 1.31,2.93, p<0.01) that of patients without TBI during the 6-year follow-up period after index health care use. Our study concludes that patients with TBI are at higher risk for subsequent MS over a 6-year follow-up period. PMID- 22044111 TI - Micro-CT analyses of apical enlargement and molar root canal complexity. AB - AIM: To compare the effectiveness of two rotary hybrid instrumentation techniques with focus on apical enlargement in molar teeth and to quantify and visualize spatial details of instrumentation efficacy in root canals of different complexity. METHODOLOGY: Maxillary and mandibular molar teeth were scanned using X-ray microcomputed tomography. Root canals were prepared using either a GT/Profile protocol or a RaCe/NiTi protocol. Variables used for evaluation were the following: distance between root canal surfaces before and after preparation (distance after preparation, DAP), percentage of root canal area remaining unprepared and increase in canal volume after preparation. Root canals were classified according to size and complexity, and consequences of unprepared portions of narrow root canals and intraradicular connections/isthmuses were included in the analyses. One- and two-way anova were used in the statistical analyses. RESULTS: No difference was found between the two techniques: DAP(apical third) (P = 0.590), area unprepared(apical-third) (P = 0.126) and volume increase(apical-third) (P = 0.821). Unprepared root canal area became larger in relation to root canal size and complexity, irrespective of the technique used. Percentage of root canal area remaining unprepared was significantly lower in small root canals and complex systems compared to large root canals. The isthmus area per se contributed with a mean of 17.6%, and with a mean of 25.7%, when a narrow root canal remained unprepared. CONCLUSIONS: The addition of isthmuses did not significantly alter the ratio of instrumented to unprepared areas at total root canal level. Distal and palatal root canals had the highest level of unprepared area irrespective of the two instrumentation techniques examined. PMID- 22044113 TI - Ultrafast vibrational frequency shifts induced by electronic excitations: naphthols in low dielectric media. AB - We study the solvent-induced frequency shifts of the OH-stretching mode of 1 naphthol and 2-naphthol in nonpolar/weakly polar solvents, subject to electronic excitation, with ultrafast UV/mid-infrared pump-probe spectroscopy and theoretical modeling based on Pullin's perturbative treatment of vibrational solvatochromic effects. The model is parametrized at the density functional theory (DFT) level, including the B3LYP/TZVP and TD-B3LYP/TZVP descriptions, for the naphthol chromophores in the S(0)- and (1)L(b)-states and accounts for both the static and the optical dielectric response of the solvent on time scales comparable to that of the OH-stretching vibrational motions. The favorable comparison between experimental and theoretical values of the solvent-induced vibrational frequency shifts suggests that the ultrafast dielectric response of the solvent contributes predominantly to the solvatochromic shifts in solvents of moderate polarity where specific solute-solvent interactions are absent. PMID- 22044112 TI - In vitro folding of KvAP, a voltage-gated K+ channel. AB - In this contribution, we report in vitro folding of the archaebacterial voltage gated K(+) channel, K(v)AP. We show that in vitro folding of the K(v)AP channel from the extensively unfolded state requires lipid vesicles and that the refolded channel is biochemically and functionally similar to the native channel. The in vitro folding process is slow at room temperature, and the folding yield depends on the composition of the lipid bilayer. The major factor influencing refolding is temperature, and almost quantitative refolding of the K(v)AP channel is observed at 80 degrees C. To differentiate between insertion into the bilayer and folding within the bilayer, we developed a cysteine protection assay. Using this assay, we demonstrate that insertion of the unfolded protein into the bilayer is relatively fast at room temperature and independent of lipid composition, suggesting that temperature and bilayer composition influence folding within the bilayer. Further, we demonstrate that in vitro folding provides an effective method for obtaining high yields of the native channel. Our studies suggest that the K(v)AP channel provides a good model system for investigating the folding of a multidomain integral membrane protein. PMID- 22044114 TI - Biochemical and pharmacological characterization of nuclear urotensin-II binding sites in rat heart. AB - BACKGROUND AND PURPOSE During the past decade, a few GPCRs have been characterized at the nuclear membrane where they exert complementary physiological functions. In this study, we investigated (1) the presence of a functional urotensin-II (U-II) receptor (UT) in rat heart nuclear extracts and (2) the propensity of U-II and U-II-related peptide (URP) to cross the plasma membrane in a receptor-independent manner. EXPERIMENTAL APPROACH Biochemical and pharmacological methods including competitive binding assays, photoaffinity labelling, immunoblotting as well as de novo RNA synthesis were used to characterize the presence of functional UT receptors in rat heart nuclei. In addition, confocal microscopy and flow cytometry analysis were used to investigate the cellular uptake of fluorescent U-II and URP derivatives. KEY RESULTS The presence of specific U-II binding sites was demonstrated in rat heart nuclear extracts. Moreover, such subcellular localization was also observed in monkey heart extracts. In vitro transcription initiation assays on rat, freshly isolated, heart nuclei suggested that nuclear UT receptors are functional, and that U-II, but not URP, participates in nuclear UT-associated gene expression. Surprisingly, hU-II and URP efficiently crossed the plasma membrane in a receptor independent mechanism involving endocytosis through caveolin-coated pits; this uptake of hU-II, but not that of URP, was dependent on extracellular pH. CONCLUSION Our results suggest that (1) U-II and URP can differentially modulate nuclear UT functions such as gene expression, and (2) both ligands can reach the internal cellular space through a receptor-independent mechanism. PMID- 22044115 TI - Quantifying plaque during orthodontic treatment:. AB - OBJECTIVE: To evaluate the literature on different methods of scoring plaque in patients with fixed orthodontic appliances. MATERIALS AND METHODS: A systematic electronic and hand search using MEDLINE and PubMed was conducted. RESULTS: Most orthodontic trials have used the original Silness and Loe plaque index. Indices vary in several potentially important aspects. Only two papers have reported reproducibility of methods of plaque scoring in orthodontic patients. CONCLUSION: Some plaque indices are inappropriate for orthodontic patients. Newer digital planimetric methods are promising if more complex. There is a need to further assess the reproducibility and practicability of the advocated methods. PMID- 22044116 TI - Longitudinal assessment of periodontal status in patients with nickel allergy treated with conventional and nickel-free braces. AB - OBJECTIVE: To perform a longitudinal comparison of periodontal status in allergic individuals treated with conventional and nickel-free braces. MATERIALS AND METHODS: Forty-two individuals allergic to nickel were randomly divided into two groups: those receiving conventional braces (n = 21) and those receiving nickel free braces (n = 21). Periodontal status (gingival hyperplasia, change in color and bleeding) was assessed before treatment (T0) and at 3-month intervals for 12 months (T1, T2, T3, and T4), using the Loe Index. Evaluations were performed blindly by a single, calibrated examiner, followed by prophylaxis and orientations regarding oral hygiene. Data were analyzed using the Mann-Whitney U test for comparisons of the gingival index between groups and Friedman's test for successive comparisons between sessions in the same group (P <= .05). RESULTS: Periodontal status did not differ between groups in the initial 9 months of treatment, whereas significant differences were found at T3 and T4 (.039 and .047, respectively). Individuals wearing conventional appliances had higher mean gingival index scores than those wearing nickel-free braces. CONCLUSION: Individuals with an allergy to nickel exhibit better periodontal health when treated with nickel-free braces than with conventional braces. PMID- 22044117 TI - Deflection load characteristics of laser-welded orthodontic wires. AB - OBJECTIVE: To compare the deflection load characteristics of homogeneous and heterogeneous joints made by laser welding using various types of orthodontic wires. MATERIALS AND METHODS: Four kinds of straight orthodontic rectangular wires (0.017 inch * 0.025 inch) were used: stainless-steel (SS), cobalt-chromium nickel (Co-Cr-Ni), beta-titanium alloy (beta-Ti), and nickel-titanium (Ni-Ti). Homogeneous and heterogeneous end-to-end joints (12 mm long each) were made by Nd:YAG laser welding. Two types of welding methods were used: two-point welding and four-point welding. Nonwelded wires were also used as a control. Deflection load (N) was measured by conducting the three-point bending test. The data (n = 5) were statistically analyzed using analysis of variance/Tukey test (P < .05). RESULTS: The deflection loads for control wires measured were as follows: SS: 21.7 +/- 0.8 N; Co-Cr-Ni: 20.0 +/- 0.3 N; beta-Ti: 13.9 +/- 1.3 N; and Ni-Ti: 6.6 +/- 0.4 N. All of the homogeneously welded specimens showed lower deflection loads compared to corresponding control wires and exhibited higher deflection loads compared to heterogeneously welded combinations. For homogeneous combinations, Co-Cr-Ni/Co-Cr-Ni showed a significantly (P < .05) higher deflection load than those of the remaining homogeneously welded groups. In heterogeneous combinations, SS/Co-Cr-Ni and beta-Ti/Ni-Ti showed higher deflection loads than those of the remaining heterogeneously welded combinations (significantly higher for SS/Co-Cr-Ni). Significance (P < .01) was shown for the interaction between the two factors (materials combination and welding method). However, no significant difference in deflection load was found between four point and two-point welding in each homogeneous or heterogeneous combination. CONCLUSION: Heterogeneously laser-welded SS/Co-Cr-Ni and beta-Ti/Ni-Ti wires provide a deflection load that is comparable to that of homogeneously welded orthodontic wires. PMID- 22044118 TI - T-cell-inducing vaccines - what's the future. AB - In the twentieth century vaccine development has moved from the use of attenuated or killed micro-organisms to protein sub-unit vaccines, with vaccine immunogenicity assessed by measuring antibodies induced by vaccination. However, for many infectious diseases T cells are an important part of naturally acquired protective immune responses, and inducing these by vaccination has been the aim of much research. The progress that has been made in developing effective T-cell inducing vaccines against viral and parasitic diseases such as HIV and malaria is discussed, along with recent developments in therapeutic vaccine development for chronic viral infections and cancer. Although many ways of inducing T cells by vaccination have been assessed, the majority result in low level, non-protective responses. Sufficient clinical research has now been conducted to establish that replication-deficient viral vectored vaccines lead the field in inducing strong and broad responses, and efficacy studies of T-cell-inducing vaccines against a number of diseases are finally demonstrating that this is a valid approach to filling the gaps in our defence against not only infectious disease, but some forms of cancer. PMID- 22044119 TI - Design, synthesis, and qualitative structure-activity evaluations of novel beta secretase inhibitors as potential Alzheimer's drug leads. AB - We have identified highly selective imidazopyridines armed with benzimidazol and/or arylimidazole as potent beta-secretase inhibitors. The most effective and selective analogues demonstrated low nanomolar potency for the BACE1 enzyme as measured by FRET and cell-based (ELISA) assays and exhibited comparable affinity (KI) and high ligand efficiency (LE). In addition, these motifs were highly selective (>200) against the structurally related aspartyl protease BACE2. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on the previously reported hydroxyethylene transition state inhibitor derived from isophthalic acid I. Of the most potent compounds, 34 displayed an IC50 for BACE1 of 18 nM and exhibited cellular activity with an EC50 of 37 nM in the cell-based ELISA assay, as well as high affinity (KI=17 nM) and ligand efficiency (LE=1.7 kJ/mol). Compound 34 was found to be 204-fold more selective for BACE1 compared to the closely related aspartyl protease BACE2. PMID- 22044120 TI - Exploring a water/energy trade-off in regional sourcing of livestock feed crops. AB - Feed production constitutes a major portion of the energy and water resource inputs in modern livestock production. Schemes to reduce these inputs may include local sourcing of animal feed. However, in water stressed regions where irrigation of feed crops is necessary, a trade-off between local sourcing (with high water stress) and transport from less water stressed regions can occur. We demonstrate this trade-off in the U.S. by combining state-level irrigation water use and pumping energy demand from USDA surveys with fertilizer and transportation energy demands for producing major feed crops (corn grain, soybean, alfalfa hay, corn silage) in each state and delivering them to two hypothetical dairy farms located in Kersey, CO and Rosendale, WI. A back-up technology approach is employed to express freshwater resource depletion in units of energy, allowing direct comparison with other energy resource demands. Corn grain, soybean, and alfalfa hay delivered to CO demonstrate a clear trade-off between transportation energy (proportional to the distance between CO and the production state) and water stress. On the other hand, transportation burdens dominate for corn silage, making local production most attractive, even in water stressed regions. All crops delivered to WI (a region of low water stress and minimal irrigation) are dominated by transportation burdens, making local production preferable, but this is clearly not a universal principal, as other cases show. This paper quantitatively elucidates the water-energy trade-off in sourcing feed for livestock and the method is expected to be applicable in managing supply chain logistics of other farm commodities. PMID- 22044121 TI - Higher order classical density functional theory for branched chains and rings. AB - We develop a general density functional theory for polyatomic molecules by taking the complete association limit of Wertheim's thermodynamic perturbation theory in a general way. By enforcing the complete association limit at an early point in the derivation and introducing the concept of molecular graphs, a general form for the free energy functional and segment densities are developed for both rigid and semiflexible molecules. The theory is applicable to branched chains, rings, or any other molecular structure. As an example the theory is applied as a second order perturbation theory to the case of molecules with a rigid three segment head and a fully flexible tail in a slit pore where bond angle of the rigid portion is an independent variable. PMID- 22044122 TI - Intranasal calcitonin reducing bone pain in a patient with Camurati-Engelmann disease. PMID- 22044125 TI - Unusual case of desmoplastic fibroblastoma (collagenous fibroma) with ulceration on toe: mimicking diabetic foot ulcer. PMID- 22044123 TI - Case-control and family-based association studies of novel susceptibility locus 8q24 in nonsyndromic cleft lip with or without cleft palate in a Southern Han Chinese population located in Guangdong Province. AB - Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital malformations and a susceptibility locus on chromosome 8q24 has been replicated as a genetic risk factor for NSCL/P in patients of European and Asian descent. However, given considerable variations in allele frequencies across geographical regions studied, the aim of this study was to investigate the association of rs987525 located at 8q24 with NSCL/P only among the southern Han Chinese population from Guangdong province. We recruited 216 NSCL/P cases, their parents, and 200 controls to conduct case-control analysis and family-based association studies. Genotyping of rs987525 was carried out by the matrix assisted laser desorption ionization-time of flight mass spectrometry method. Case-control analysis showed allele and genotype distributions for rs987525 were not significantly associated with the risk of NSCL/P in our study population. Similar results were found when all cases were stratified into cleft lip only and cleft lip with cleft palate. A transmission disequilibrium test showed no statistically significant transmission of A nor C alleles and family-based association test (FBAT) analysis provided no evidence of NSCL/P risk with single markers. These results do not provide evidence for an association between rs987525 at 8q24 and the risk of NSCL/P in the southern Han Chinese population from Guangdong province. PMID- 22044126 TI - Screening method for isopeptides from small ubiquitin-related modifier-conjugated proteins by ion mobility mass spectrometry. AB - Posttranslational modification by the small ubiquitin-related modifier (SUMO) is a highly regulated modification, which is often restricted to very specific cellular events. A number of analytical strategies for identification of SUMOylated proteins have been previously reported in the literature. A new screening method for SUMOylated peptides based on ion mobility mass spectrometry is presented. Using poly-SUMO2 as a model system, a two-enzyme trypsin/chymotrypsin digestion was performed to reduce the size of the isopeptide conjugated to the substrate lysine residue. Traveling wave ion mobility mass spectrometry was used to screen for peptides containing the QQQTGG isopeptide tag from SUMO, which increases the mass and size of the peptide by 618 Da. This increase in mass along with solution conditions to promote higher charge states allows the isopeptides to be separated from the typically smaller and lesser charged linear peptides. On the basis of these findings, this method can be used as a quick and easy screening method for identifying possible SUMO isopeptides. PMID- 22044127 TI - Unilateral implicit motor learning deficit in developmental dyslexia. AB - It has been suggested that developmental dyslexia involves various literacy, sensory, motor skill, and processing speed deficits. Some recent studies have shown that individuals with developmental dyslexia exhibit implicit motor learning deficits, which may be related to cerebellar functioning. However, previous studies on implicit motor learning in developmental dyslexics have produced conflicting results. Findings from cerebellar lesion patients have shown that patients' implicit motor learning performance varied when different hands were used to complete tasks. This suggests that dyslexia may have different effects on implicit motor learning between the two hands if cerebellar dysfunction is involved. To specify this question, we used a one-handed version of a serial reaction time task to compare the performance of 27 Chinese children with developmental dyslexics with another 27 age-matched children without reading difficulties. All the subjects were students from two primary schools, Grades 4 to 6. The results showed that children with developmental dyslexic responded more slowly than nondyslexic children, and exhibited no implicit motor learning in the condition of left-hand response. In contrast, there was no significant difference in reaction time between two groups of children when they used the right hand to respond. This finding indicates that children with developmental dyslexia exhibited normal motor skill and implicit motor learning ability provided the right hand was used. Taken together, these results suggested that Chinese children with developmental dyslexia exhibit unilateral deficits in motor skill and implicit motor learning in the left hand. Our findings lend partial support to the cerebellar deficit theory of developmental dyslexia. PMID- 22044128 TI - The effects of age and production mode on the bilingual performance of Turkish learners of English in a serial recall task. AB - The cognitive resources available to the working memory system are finite. Under conditions of cognitive overload, a compromise may need to be made between the demands of storage and processing. Research suggests that the cognitive cost of partially automated transcription processes adversely affects written language production in children. Thus, children may be expected to perform the same task better orally than in writing. In order to determine whether this is the case in a Turkish context, three samples of participants, comprising 16 undergraduate students, 16 fifth-grade and 16 third-grade pupils, were required to perform oral and written serial recall of Turkish word lists. Recall mode did not interact significantly with age. In the adult sample, the combined samples of schoolchildren, and the fifth-grade sample of children written recall was significantly better than oral recall. This may reflect the transparency of Turkish orthography and/or the age of the participating children. However, when the test was administered in English, no effect of modality was observed in children. This suggests that when the additional cognitive costs of processing a less automated language are combined with transcription costs, the resources available to children in working memory for the storage of information are depleted. PMID- 22044129 TI - Morningness-eveningness, use of stimulants, and minor psychiatric disorders among undergraduate students. AB - Morningness-eveningness dimension in humans have been indicated to influence social behavior and individual health. The aim of the present study was to investigate the association of the morningness-eveningness dimension with behavioral and health aspects in a sample of undergraduate students. We assessed demographic data; the Pittsburgh Sleep Quality Index was used to evaluate sleep quality; the Morningness/Eveningness Questionnaire to determine morningness eveningness, and the Self-Reporting Questionnaire to assess minor psychiatric disorders. A total of 372 students (66.7% females), on average 21.6 years old, participated in this study. Among them, 92.2% did not smoke, 58.9% engaged in physical activities, and 19.7% were night-shift workers. In regard to morningness eveningness, 55.9% of the participants were intermediate between evening (39.5%) and morning (4.6%) types. Poor sleep quality (OR = 1.89), minor psychiatric disorders (OR = 1.92), and tobacco consumption (OR = 3.65) predominated among evening types. Evening types were predominantly males (OR = 1.72). This study suggests that evening types are more vulnerable to sleep and psychiatric disturbances, and tend to smoke more than morning types. PMID- 22044130 TI - Multiple caregivers' touch interactions with young children among the Bofi foragers in Central Africa. AB - The current study examined the use of three types of touch (caregiving, active social-affectionate, and passive social-affectionate) by caregivers with young children among the Bofi foragers, a seminomadic group of hunter-gatherers in Central Africa. With the purpose of providing a more holistic view of touch interactions in early childhood, compared to extant Western mother-centric views, this study documents stylistic touch patterns used by multiple caregivers (mother, father, adult relatives, and juvenile relatives) with Bofi forager children. Thirty-five Bofi forager children, between 18 and 59 months of age, and their various caregivers were naturalistically observed over 12 daylight hours using a focal child observational technique. Frequencies of each type of touch and the rank order of types of touch that children received were compared between caregivers and examined by child age and gender. Even though nonmaternal caregivers showed high physical involvement with children, mothers exemplified the highest level of involvement. Overall, passive social-affectionate touch was utilized the most by all types of caregivers. Mothers used more caregiving touch, and fathers and adult relatives had similar frequencies of caregiving touch and active social-affectionate touch. In contrast, juvenile relatives showed more active social-affectionate touch with focal children. This study highlights the importance of examining multiple caregivers and physical interactions when studying early childhood experiences. Furthermore, by focusing on multiple caregivers and multiple types of touch, this study provides a more thorough characterization of the touch experiences of young children than previous studies of touch. Finally, the current study exemplifies the value of considering non Western populations when investigating touch interactions. PMID- 22044131 TI - Inverse gender gap in Germany: social dominance orientation among men and women. AB - Across cultures studies show that men score higher on social dominance orientation than women. This gender gap is considered invariant, but conflicting explanations are discussed: Some authors refer to evolutionary psychology and perceive the gender gap to be driven by sociobiological factors. Other authors argue that social roles or gender-stereotypical self-construals encouraged by intergroup comparisons are responsible for attitudinal gender difference. In Study 1 we analyzed sex differences in social dominance orientation in three German probability surveys (each n > 2300). Unexpectedly, the analyses yielded an inverse gender gap with higher values for social dominance orientation in women than in men. Interactions with age, education, political conservatism, and perceived inequity indicated that the inverse gender gap can be mainly attributed to older, conservative, (and less educated) respondents, and those who feel they get their deserved share. In Study 2 we replicated the well-known gender gap with men scoring higher than women in social dominance orientation among German students. Results are interpreted on the basis of biocultural interaction, which integrates the sociobiological, social role, and self-construal perspectives. Our unusual findings seem to reflect a struggle for status by members of low-status groups who consider group-based hierarchy the most promising option to improve their status. While younger women take advantage of a relational, feminine self construal that leads to lower social dominance orientation in young women than in young men, older women are supposed to profit from an agentic self-construal that results in stronger social dominance orientation values. Specific characteristics of the culture in Germany seem to promote this strategy. Here, we discuss the female ideal of the national socialist period and the agentic female social role in the post-war era necessitated by the absence of men. PMID- 22044132 TI - Analysis of the multidimensionality of hallucination-like experiences in clinical and nonclinical Spanish samples and their relation to clinical symptoms: implications for the model of continuity. AB - Numerous studies have found that hallucinatory experiences occur in the general population. But to date, few studies have been conducted to compare clinical and nonclinical groups across a broad array of clinical symptoms that may co-occur with hallucinations. Likewise, hallucination-like experiences are measured as a multidimensional construct, with clinical and subclinical components related to vivid daydreams, intrusive thoughts, perceptual disturbance, and clinical hallucinatory experiences. Nevertheless, these individual subcomponents have not been examined across a broad spectrum of clinically disordered and nonclinical groups. The goal of the present study was to analyze the differences and similarities in the distribution of responses to hallucination-like experience in clinical and nonclinical populations and to determine the relation of these hallucination-like experiences with various clinical symptoms. These groups included patients with schizophrenia, non-psychotic clinically disordered patients, and a group of individuals with no psychiatric diagnoses. The results revealed that hallucination-like experiences are related to various clinical symptoms across diverse groups of individuals. Regression analysis found that the Psychoticism dimension of the Symptom Check List (SCL-90-R) was the most important predictor of hallucination-like experiences. Additionally, increased auditory and visual hallucination was the only subcomponent that differentiated schizophrenic patients from other groups. This distribution of responses in the dimensions of hallucination-like experiences suggests that not all the dimensions are characteristic of people hearing voices. Vivid daydreams, intrusive thoughts, and auditory distortions and visual perceptual distortions may represent a state of general vulnerability that does not denote a specific risk for clinical hallucinations. Overall, these results support the notion that hallucination-like experiences are closer to a quasi-continuum approach and that total scores on these scales explain a state of vulnerability to general perceptual disturbance. PMID- 22044133 TI - Context effects: the role of collectivism as a moderator. AB - Social cognition experts have shown that participants' answers to research questions can be influenced by previous questions, something known as context effects. It has been suggested that participants from collectivist cultures pay more attention to the context, resulting in larger context effects. The present investigation examined context effects in an experiment that involved manipulating the order in which two questions, one about satisfaction with life as a whole and one about satisfaction with romantic life, were answered by a representative sample of participants from Mexico City. The results were consistent with other investigations that used samples from collectivistic cultures. Participants' responses to questions about satisfaction are influenced by a previous question, and country of origin affects the amount of attention given to the context. The implications of these results are discussed. PMID- 22044134 TI - Reacting to headline news: circumstances leading to causal explanations versus implicational concerns. AB - How do people react to the headline news they receive? According to the model of people as intuitive scientists (Kelley, 1972; Ross, 1977), people-like scientists make causal explanations (i.e., why did an event take place?) and assign responsibility to the person, the situation, or both. However, a more recently proposed social-functionalist model (Tetlock, 2002) views people less as intuitive scientists trying to understand the world and more as intuitive prosecutors trying to protect a fragile social order. Thus, implicational concerns (i.e., how would it affect people's lives, properties, and liberties?) with the news can also be likely reactions. Given the prescriptions of these models, the present authors tested the hypotheses that news reports evoke both causal explanations and implicational concerns among viewers, and that the degree of the two reactions depends on the valence (positive vs. negative) and theme (whether it is unusual or social order-linked) of the news. Singaporeans (N = 80) read one piece of headline news that represented a crossed level of valence (negative vs. positive) and theme (unusual vs. social order), and indicated the likelihood of causal explanations and implicational concerns as their first response to it. As hypothesized, positive news led to a greater likelihood of showing implicational concerns than of making causal explanations, the difference being reversed in the case of negative news; unusual news led to a greater likelihood of making causal explanations than of showing implication concerns; the likelihood of having implicational concerns with news related to social order was higher than making that of causal explanations; and the two responses were equally likely in the case of negative news. Overall, these results support a view of people as intuitive prosecutors interested in both causal explanations of and implicational concerns with a news report. PMID- 22044135 TI - Environmentalism as a trait: gauging people's prosocial personality in terms of environmental engagement. AB - According to Hardin (1968), environmental deterioration stems from self-interest undermining people's resource conservation in the collective interest. Not surprisingly, selfless prosocial motives, such as personal feelings of moral obligation, have often been recognized as a key force behind people's environmentalism. In our research, we anticipated that environmentalists-people with an inclination for pro-environmental engagement-would possess a propensity to generally act prosocially. In an extension of previous work, we expected that a well-established self-report measure of past conservation behavior would predict people's active participation in a psychological experiment. Based on subjects' degree of environmental engagement, originally established in 2003, we re-contacted a sample of 502 persons in 2005. Of these 502 (68.5% low, 31.5% high in environmentalism), 131 showed up for the announced experiment. Among those participants, we found that environmentalists' prosocial personalities were additionally reflected in their social value orientations. Ninety percent of the environmentalists turned out to be prosocials, whereas only 65% of the less environmentally engaged subjects were prosocials. Overall, our findings lend credit to a notion of environmentalism as an indicator of even subtle quantitative differences in a person's prosocial trait level. By and large, environmentalists acted more prosocially even in mundane activities unrelated to environmental conservation. Additional evidence comes from the commons dilemma experiment in which the participants partook. There, we generally found comparatively more cooperation with others for the collective good from people high in environmentalism. Our findings represent circumstantial evidence for a prosocial propensity dimension along which people differ, and which is also reflected in people's pro-environmental behavioral performance. If, however, environmentalism has to be regarded as indicative of a prosocial trait rather than a state-like motive, high hopes for moral norms and other prosocial motives in environmental conservation do not seem warranted. PMID- 22044136 TI - Mushroom tyrosinase inhibitors from mung bean (Vigna radiatae L.) extracts. AB - A seventy percent ethanol from mung bean (Vigna radiatae L.) was extracted further with CH(2)Cl(2), EtOAc and n-BuOH to afford four fractions: CH(2)Cl(2) soluble, EtOAc-soluble, n-BuOH-soluble and residual extract fractions. When using l-3,4-dihydroxyphenylalanine as the substrate for mushroom tyrosinase, the EtOAc soluble fractions showed the highest inhibitory activity. Two pure flavonoid compounds, vitexin and isovitexin, were isolated (using the enzyme assay-guided fractionation method) from the EtOAc-soluble fractions. Vitexin and isovitexin showed high inhibitory activities, with IC(50) values of 6.3 and 5.6 mg/ml, respectively. This is the first study on the active compositions of azuki beans against mushroom tyrosinase. PMID- 22044137 TI - Molecular detection of circulating Sezary cells in patients with mycosis fungoides: could it predict future development of secondary Sezary syndrome? A single-institution experience. AB - While the majority of patients with early-stage mycosis fungoides (MF) have an excellent prognosis, a few cases progress to secondary Sezary syndrome (sSS), which carries a dismal clinical outcome. We retrospectively analyzed 135 cases of MF/SS and correlated molecular detection of T-cell clones in the skin and blood with other clinicopathologic findings. When stratified by the diagnoses, patients with MF demonstrated a 26.5% (31/117) positive rate for a blood T-cell clone, of which 50% (10/20) had an identical T-cell clone in the skin. Follow-up evaluation showed conversion into sSS or leukemic phase in 50% (5/10) of cases with a positive blood T-cell clone (estimated mean interval 41.8 months) in comparison to no cases in the group without a clone (0/31). Interestingly, 4/5 cases of sSS had an identical T-cell clone in the skin, while the remaining case did not have the test performed on skin for clonal comparison. Kaplan-Meier survival analysis demonstrated a poor clinical outcome in the group with a blood T-cell clone, in comparison with the group without, in overall survival (p < 0.0001) and progression-free survival (p < 0.0001; HR = 22.6). These findings suggest that molecular detection of a blood T-cell clone may have a role in predicting sSS. Due to amplification of non-neoplastic T-cell expansion in a significant number of cases, comparison of blood T-cell clones with skin may have confirmatory value. PMID- 22044138 TI - Expression of ABCB5 gene in hematological malignances and its significance. AB - We examined ABCB5 gene expression using real-time polymerase chain reaction (PCR) in leukemia cells from 29 patients with acute lymphoblastic leukemia (ALL), 24 patients with chronic lymphocytic leukemia (CLL), 42 with acute myeloid leukemia (AML), 22 with chronic myeloid leukemia (CML), 17 with lymphoma and 10 with multiple myeloma (MM). It was confirmed that expression of the ABCB5 gene is highly increased in B-precursor ALL and French-American-British (FAB) M1 and M2 types of AML and lymphoma. The ABCB5 gene is expressed more highly in patients with relapsed or refractory disease than in patients with drug sensitive acute leukemia. Furthermore, there was an evident positive correlation between ABCB5 mRNA expression and MDR1 mRNA expression, but no correlation with MRP mRNA expression or BCRP mRNA expression. Quantification of the ABCB5 gene by real-time PCR offers particular promise as a prognostic marker and a marker for drug resistance in acute leukemia. Our findings raise the possibility that ABCB5 may be responsible for both the progression and chemotherapeutic refractoriness of advanced acute leukemia, and that ABCB5-targeted approaches might therefore represent novel and translationally relevant therapeutic strategies for drug resistance in leukemia. PMID- 22044139 TI - Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice. AB - Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic beta-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-gamma (IFN-gamma) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-gamma secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development. PMID- 22044141 TI - The probe rules in single particle tracking. AB - Single particle tracking (SPT) enables light microscopy at a sub-diffraction limited spatial resolution by a combination of imaging at low molecular labeling densities and computational image processing. SPT and related single molecule imaging techniques have found a rapidly expanded use within the life sciences. This expanded use is due to an increased demand and requisite for developing a comprehensive understanding of the spatial dynamics of bio-molecular interactions at a spatial scale that is equivalent to the size of the molecules themselves, as well as by the emergence of new imaging techniques and probes that have made historically very demanding and specialized bio-imaging techniques more easily accessible and achievable. SPT has in particular found extensive use for analyzing the molecular organization of biological membranes. From these and other studies using complementary techniques it has been determined that the organization of native plasma membranes is heterogeneous over a very large range of spatial and temporal scales. The observed heterogeneities in the organization have the practical consequence that the SPT results in investigations of native plasma membranes are time dependent. Furthermore, because the accessible time dynamics, and also the spatial resolution, in an SPT experiment is mainly dependent on the luminous brightness and photostability of the particular SPT probe that is used, available SPT results are ultimately dependent on the SPT probes. The focus of this review is on the impact that the SPT probe has on the experimental results in SPT. PMID- 22044142 TI - Bilayer hydrophobic thickness and integral membrane protein function. AB - The influence of the lipid environment on the function of membrane proteins is increasingly recognized as crucial. Nevertheless, the molecular mechanisms underlying protein-lipid interactions remain obscure. Membrane lipid composition has a regulatory effect on membrane protein activity, and for a number of membrane proteins a clear correlation was found between protein activity and properties of the membrane bilayer such as fluidity. Membrane thickness is an important property of a lipid bilayer. It is expected that hydrophobic thickness match the hydrophobic thickness of transmembrane segments of integral membrane proteins. Any mismatch between the hydrophobic thicknesses of the lipid bilayer and the protein would lead to some modification in either the structure of the protein or the structure of the bilayer, or both. Consequent rearrangements may result in changes in protein activity. Here we review the behavior of several transmembrane proteins whose activity is altered by hydrophobic core thickness. PMID- 22044140 TI - Determining the orientation and localization of membrane-bound peptides. AB - Many naturally occurring bioactive peptides bind to biological membranes. Studying and elucidating the mode of interaction is often an essential step to understand their molecular and biological functions. To obtain the complete orientation and immersion depth of such compounds in the membrane or a membrane mimetic system, a number of methods are available, which are separated in this review into four main classes: solution NMR, solid-state NMR, EPR and other methods. Solution NMR methods include the Nuclear Overhauser Effect (NOE) between peptide and membrane signals, residual dipolar couplings and the use of paramagnetic probes, either within the membrane-mimetic or in the solvent. The vast array of solid state NMR methods to study membrane-bound peptide orientation and localization includes the anisotropic chemical shift, PISA wheels, dipolar waves, the GALA, MAOS and REDOR methods and again the use of paramagnetic additives on relaxation rates. Paramagnetic additives, with their effect on spectral linewidths, have also been used in EPR spectroscopy. Additionally, the orientation of a peptide within a membrane can be obtained by the anisotropic hyperfine tensor of a rigidly attached nitroxide label. Besides these magnetic resonance techniques a series of other methods to probe the orientation of peptides in membranes has been developed, consisting of fluorescence-, infrared- and oriented circular dichroism spectroscopy, colorimetry, interface-sensitive X ray and neutron scattering and Quartz crystal microbalance. PMID- 22044143 TI - Quantification of protein-protein interactions within membranes by fluorescence correlation spectroscopy. AB - The characterization of interactions between membrane proteins as they take place within the lipid bilayer poses a technical challenge, which is currently very difficult and, in many cases, impossible to overcome. The recent development of a method based in the combination two-color fluorescence cross-correlation spectroscopy with scanning of the focal volume allows the detection and quantification of interactions between biomolecules inserted in biological membranes. This powerful strategy has allowed the quantitative analysis of diverse systems, such as the association between proteins of the Bcl-2 family involved in apoptosis regulation or the binding between a growth factor and its receptor during signaling. Here, we review the last developments to quantify protein/protein interactions in lipid membranes and focus on the use of fluorescence-correlation-spectroscopy approaches for that purpose. PMID- 22044144 TI - Novel functions and binding mechanisms of carbohydrate-binding proteins determined by force measurements. AB - Cell surface carbohydrates are important targets for many cell surface receptors, and they mediate crucial biological processes ranging from pathogen infectivity to neutrophil adhesion to drug targeting. A central challenge is to identify relationships between lectin architecture and function that influence the adhesion strength, avidity, and kinetics of receptor-glycan bonds. This information is central both to understanding recognition mechanisms and to developing effective therapeutic agents for drug targeting or for preventing infection. Increasingly, force probes are used to assess structure activity relationships of both the glycan ligands and the receptors that bind them, as well as molecular mechanisms underlying binding and adhesion. This review describes recent advances in the use of different force measurement techniques to quantify receptor-glycan bond parameters, and to identify novel features of molecular mechanisms underlying recognition and adhesion. The examples discussed focus in particular on single bond rupture, surface force measurements, and micropipette manipulation. This review emphasizes the often-unique information obtained from studies of lectin interactions with carbohydrate ligands that complement more common structure determinations and solution binding studies. PMID- 22044145 TI - What can we learn from single molecule trajectories? AB - Diffusing membrane constituents are constantly exposed to a variety of forces that influence their stochastic path. Single molecule experiments allow for resolving trajectories at extremely high spatial and temporal accuracy, thereby offering insights into en route interactions of the tracer. In this review we discuss approaches to derive information about the underlying processes, based on single molecule tracking experiments. In particular, we focus on a new versatile way to analyze single molecule diffusion in the absence of a full analytical treatment. The method is based on comprehensive comparison of an experimental data set against the hypothetical outcome of multiple experiments performed on the computer. Since Monte Carlo simulations can be easily and rapidly performed even on state-of-the-art PCs, our method provides a simple way for testing various - even complicated - diffusion models. We describe the new method in detail, and show the applicability on two specific examples: firstly, kinetic rate constants can be derived for the transient interaction of mobile membrane proteins; secondly, residence time and corral size can be extracted for confined diffusion. PMID- 22044146 TI - Disordered proteins and network disorder in network descriptions of protein structure, dynamics and function: hypotheses and a comprehensive review. AB - During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local, mesoscopic and global network disorder on changes in protein structure and dynamics. We introduce a new classification of protein networks into 'cumulus type', i.e., those similar to puffy (white) clouds, and 'stratus-type', i.e., those similar to flat, dense (dark) low-lying clouds, and relate these network types to protein disorder dynamics and to differences in energy transmission processes. In the first class, there is limited overlap between the modules, which implies higher rigidity of the individual units; there the conformational changes can be described by an 'energy transfer' mechanism. In the second class, the topology presents a compact structure with significant overlap between the modules; there the conformational changes can be described by 'multi trajectories'; that is, multiple highly populated pathways. We further propose that disordered protein regions evolved to help other protein segments reach 'rarely visited' but functionally-related states. We also show the role of disorder in 'spatial games' of amino acids; highlight the effects of intrinsically disordered proteins (IDPs) on cellular networks and list some possible studies linking protein disorder and protein structure networks. PMID- 22044147 TI - The role of intrinsically disordered regions in the structure and functioning of small heat shock proteins. AB - Small heat shock proteins (sHsp) form a large ubiquitous family of proteins expressed in all phyla of living organisms. The members of this family have low molecular masses (13-43 kDa) and contain a conservative alpha-crystallin domain. This domain (about 90 residues) consists of several beta-strands forming two beta sheets packed in immunoglobulinlike manner. The alpha-crystallin domain plays an important role in formation of stable sHsp dimers, which are the building blocks of the large sHsp oligomers. A large N-terminal domain and a short C-terminal extension flank the alpha-crystallin domain. Both the N-terminal domain and the C terminal extension are flexible, susceptible to proteolysis, prone to posttranslational modifications, and are predominantly intrinsically disordered. Differently oriented N-terminal domains interact with each other, with the core alpha-crystallin domain of the same or neighboring dimers and play important role in formation of large sHsp oligomers. Phosphorylation of certain sites in the N terminal domain affects the sHsp quaternary structure, the sHsp interaction with target proteins and the sHsp chaperone-like activity. The C-terminal extension often carrying the conservative tripeptide (I/V/L)-X-(I/V/L) is capable of binding to a hydrophobic groove on the surface of the core alpha-crystallin domain of neighboring dimer, thus affecting the plasticity and the overall structure of sHsp oligomers. The Cterminal extension interacts with target proteins and affects their interaction with the alpha-crystallin domain increasing solubility of the complexes formed by sHsp and their targets. Thus, disordered N- and C-terminal sequences play important role in the structure, regulation and functioning of sHsp. PMID- 22044148 TI - Understanding pre-structured motifs (PreSMos) in intrinsically unfolded proteins. AB - Intrinsically unfolded proteins (IUPs) do not obey the golden rule of structural biology, 3D structure = function, as they manifest their inherent functions without resorting to three-dimensional structures. Absence of a compact globular topology in these proteins strongly implies that their ligand recognition processes should involve factors other than spatially well-defined binding pockets. Heteronuclear multidimensional (HetMulD) NMR spectroscopy assisted with a stable isotope labeling technology is a powerful tool for quantitatively investigating detailed structural features in IUPs. In particular, it allows us to delineate the presence and locations of pre-structured motifs (PreSMos) on a per-residue basis. PreSMos are the transient local structural elements that presage target-bound conformations and act as specificity determinants for IUP recognition by target proteins. Here, we present a brief chronicle of HetMulD NMR studies on IUPs carried out over the past two decades along with a discussion on the functional significance of PreSMos in IUPs. PMID- 22044149 TI - Comprehensive comparative assessment of in-silico predictors of disordered regions. AB - Intrinsic disorder is relatively common in proteins, plays important roles in numerous cellular activities, and its prevalence was implicated in various human diseases. However, annotations of the disorder lag behind the rapidly increasing number of known protein chains. The last decade observed development of a relatively large number of in-silico methods that predict the disorder using the protein sequence as their input. We perform a first-of-its kind comprehensive empirical evaluation of the disorder predictors which is characterized by three novel aspects, (1) we evaluate the quality of the disorder predictions at the residue, segment, and chain levels; (2) we consider a large number of published and accessible to the end user predictors that are evaluated on a relatively big dataset with close to 500 proteins; and (3) we assess statistical significance of differences between the considered methods. Our study reveals that there is no universally superior predictor and that the top-performing methods are complementary. We show that while recent consensus-based predictors outperform other considered methods for the residue-level predictions, some older methods perform better for the prediction of the disordered segments. Our analysis indicates that certain predictors are biased to under-predict the disorder, while some other solutions tend to over-predict the number of the disordered residues. We also evaluate the utility of the predicted residue-level disorder for prediction of proteins with long disordered segments and prediction of the chainlevel disorder content. Lastly, we provide recommendations concerning development of a new generation of consensusbased methods and specialized methods for improved prediction of the disorder content. PMID- 22044151 TI - HSF transcription factor family, heat shock response, and protein intrinsic disorder. AB - Intrinsically disordered proteins are highly abundant in all kingdoms of life, and several protein functional classes, such as transcription factors, transcriptional regulators, hub and scaffold proteins, signaling proteins, and chaperones are especially enriched in intrinsic disorder. One of the unique cellular reactions to protein damaging stress is the so-called heat shock response that results in the upregulation of heat shock proteins including molecular chaperones. This molecular protective mechanism is conserved from prokaryotes to eukaryotes and allows an organism to respond to various proteotoxic stressors, such as heat shock, oxidative stress, exposure to heavy metals, and drugs. The heat shock response- related proteins can be expressed during normal conditions (e.g., during the cell growth and development) or can be induced by various pathological conditions, such as infection, inflammation, and protein conformation diseases. The initiation of the heat shock response is manifested by the activation of the heat shock transcription factors HSF 1, part of a family of related HSF transcription factors. This review analyzes the abundance and functional roles of intrinsic disorder in various heat shock transcription factors and clearly shows that the heat shock response requires HSF flexibility to be more efficient. PMID- 22044150 TI - How random are intrinsically disordered proteins? A small angle scattering perspective. AB - While the crucial role of intrinsically disordered proteins (IDPs) in the cell cycle is now recognized, deciphering their molecular mode of action at the structural level still remains highly challenging and requires a combination of many biophysical approaches. Among them, small angle X-ray scattering (SAXS) has been extremely successful in the last decade and has become an indispensable technique for addressing many of the fundamental questions regarding the activities of IDPs. After introducing some experimental issues specific to IDPs and in relation to the latest technical developments, this article presents the interest of the theory of polymer physics to evaluate the flexibility of fully disordered proteins. The different strategies to obtain 3-dimensional models of IDPs, free in solution and associated in a complex, are then reviewed. Indeed, recent computational advances have made it possible to readily extract maximum information from the scattering curve with a special emphasis on highly flexible systems, such as multidomain proteins and IDPs. Furthermore, integrated computational approaches now enable the generation of ensembles of conformers to translate the unique flexible characteristics of IDPs by taking into consideration the constraints of more and more various complementary experiment. In particular, a combination of SAXS with high-resolution techniques, such as x ray crystallography and NMR, allows us to provide reliable models and to gain unique structural insights about the protein over multiple structural scales. The latest neutron scattering experiments also promise new advances in the study of the conformational changes of macromolecules involving more complex systems. PMID- 22044152 TI - Disruption of the V-ATPase functionality as a way to uncouple bone formation and resorption - a novel target for treatment of osteoporosis. AB - The unique ability of the osteoclasts to resorb the calcified bone matrix is dependent on secretion of hydrochloric acid. This process is mediated by a vacuolar H+ ATPase (V-ATPase) and a chloride-proton antiporter. The structural subunit of the V-ATPase, a3, is highly specific for osteoclasts, and mutations in a3 lead to infantile malignant osteopetrosis, a phenomenon characterized by increased bone mass, an increased number of non-resorbing osteoclasts, and a complete lack of bone resorption. Importantly, these individuals have normal or even increased osteoblast numbers and bone formation suggesting that the osteoclasts, but not their resorptive capability, relay an anabolic signal, and, hence, that bone formation can be uncoupled from bone resorption when the a3 subunit is eliminated by mutations, or possibly by pharmacological intervention. The pharmacological profile of the a3 subunit as a highly specific target with a mode of action profile augmenting uncoupling and sustained bone formation, as derived from osteopetrotic patients and mice, highlights the relevance of the V ATPase in future osteoporosis drug development. However, as illustrated by numerous attempts at developing specific inhibitors of the osteoclastic V-ATPase it is a very difficult target to work with, and an inhibitor possessing the desired profile remains elusive, although highly promising approaches recently have been launched. PMID- 22044153 TI - Targeting reversible disassembly as a mechanism of controlling V-ATPase activity. AB - Vacuolar proton-translocating ATPases (V-ATPases) are highly conserved proton pumps consisting of a peripheral membrane subcomplex called V1, which contains the sites of ATP hydrolysis, attached to an integral membrane subcomplex called Vo, which encompasses the proton pore. V-ATPase regulation by reversible dissociation, characterized by release of assembled V1 sectors into the cytosol and inhibition of both ATPase and proton transport activities, was first identified in tobacco hornworm and yeast. It has since become clear that modulation of V-ATPase assembly level is also a regulatory mechanism in mammalian cells. In this review, the implications of reversible disassembly for V-ATPase structure are discussed, along with insights into underlying subunit-subunit interactions provided by recent structural work. Although initial experiments focused on glucose deprivation as a trigger for disassembly, it is now clear that V-ATPase assembly can be regulated by other extracellular conditions. Consistent with a complex, integrated response to extracellular signals, a number of different regulatory proteins, including RAVE/rabconnectin, aldolase and other glycolytic enzymes, and protein kinase A have been suggested to control V-ATPase assembly and disassembly. It is likely that multiple signaling pathways dictate the ultimate level of assembly and activity. Tissue-specific V-ATPase inhibition is a potential therapy for osteoporosis and cancer; the possibility of exploiting reversible disassembly in design of novel V-ATPase inhibitors is discussed. PMID- 22044154 TI - Regulation of V-ATPase expression in mammalian cells. AB - Vacuolar ATPases (V-ATPases) are large multisubunit complexes that actively transport protons across cellular membranes to acidify intracellular compartments, thereby serving a critical housekeeping function. In addition, VATPases are also expressed on the plasma membrane of cell types such as kidney epithelia and osteoclasts, which require high levels of proton secretion to perform their specialized activities. This multiplicity of function is achieved by the expression of numerous V-ATPase subunit isoforms that are mixed and matched to produce complexes required for each cellular activity. Multiple regulatory mechanisms are necessary to allow coordinated expression of V-ATPase subunit proteins involved in both housekeeping and specialized functions. This review will summarize studies during the last two decades that have revealed transcriptional and post-transcriptional controls that govern expression of V ATPase subunits. These studies are beginning to elucidate overarching mechanisms that permit coordinated expression of ubiquitous subunits while directing tissue specific expression of others. PMID- 22044155 TI - V-ATPase subunit interactions: the long road to therapeutic targeting. AB - Over the last three decades, V-ATPases have emerged from the obscurity of poorly understood membrane proton transport phenomena to being recognized as ubiquitous proton pumps that underlie vital cellular processes in all eukaryotic and many prokaryotic cells. These exquisitely complex molecular motors also engage in diverse specialized roles contributing to development, tissue function and pH homeostasis within complex organisms. Increasingly, mutations and misappropriation of V-ATPase function have been linked to diseases, ranging from sclerosing bone pathologies and renal tubular acidosis to bone-loss disorders and cancer metastasis. Much remains to be learned about the details of V-ATPase cell and molecular biology; nevertheless, interest in V-ATPases as potential therapeutic targets has burgeoned in recent years. In this review, we present a history of our involvement and contributions to the understanding of V-ATPase structure and function and our nascent and ongoing contributions to translating the knowledge gained from basic research on the nature of V-ATPases into tools for drug discovery. We focus here primarily on the treatment of bone-loss pathologies, like osteoporosis, and present proof-of-concept for a drug screening strategy based on targeting a3-B2 subunit interactions within the V-ATPase complex. PMID- 22044156 TI - Novel insights into V-ATPase functioning: distinct roles for its accessory subunits ATP6AP1/Ac45 and ATP6AP2/(pro) renin receptor. AB - The vacuolar (H+)-ATPase (V-ATPase) is a universal proton pump and its activity is required for a variety of cell-biological processes such as membrane trafficking, receptor-mediated endocytosis, lysosomal protein degradation, osteoclastic bone resorption and maintenance of acid-base homeostasis by renal intercalated cells. In neuronal and neuroendocrine cells, the V-ATPase is the major regulator of intragranular acidification which is indispensable for correct prohormone processing and neurotransmitter uptake. In these specialized cells, the V-ATPase is equipped with the accessory subunits ATP6AP1/Ac45 and ATP6AP2/(pro) renin receptor. Recent studies have shown that Ac45 interacts with the V0- sector of the V-ATPase complex, thereby regulating the intragranular pH and Ca2+-dependent exocytotic membrane fusion. Thus, Ac45 can be considered as a V-ATPase regulator in the neuroendocrine secretory pathway. ATP6AP2 has recently been found to be identical to the (pro) renin receptor and has a dual role: (i) in the renin-angiotensin system that also regulates V-ATPase activity; (ii) acting as an adapter by binding to both the V-ATPase and the Wnt receptor complex, thereby recruiting the receptor complex into an acidic microenvironment. We here provide an overview of the two V-ATPase accessory subunits as novel key players in V-ATPase regulation. We argue that the accessory subunits are candidate genes for V-ATPase-related human disorders and promising targets for manipulating V-ATPase functioning in vivo. PMID- 22044157 TI - Vacuolar H(+)-ATPase signaling pathway in cancer. AB - Up-regulated aerobic glycolysis is a hallmark of malignant cancers. Little is understood about the reasons why malignant tumors up-regulate glycolysis and acidify their microenvironment. Signaling pathways involved in glucose changes are numerous. However, the identity of the internal glucose signal remains obscure. In this review we address the question of the significance of vacuolar proton ATPase (V-ATPase) and its relationship to up-regulated glycolysis in tumors. We know that glycolysis is extremely sensitive to changes in pH. Importantly, the V-ATPase activity is sensitive to glucose availability. Therefore, we propose that pH acts as the glucose signal via the V-ATPase that responds to changes in intracellular pH and acts as a sensor. We hypothesize that the increase in glycolysis leads to intracellular acidification and activates the V-ATPase to maintain a more alkaline intracellular pH in tumors by up-regulating glycolysis. This review attempts to provide a comprehensive description of the current knowledge about the role of V-ATPase in cancer, highlighting its role as a key player in the pH signaling pathway. PMID- 22044159 TI - Identification of a unique double-negative regulatory T-cell population. AB - Regulatory T (Treg) cells represent one of the main mechanisms of regulating self reactive immune cells. Treg cells are thought to play a role in down-regulating immune responses to self or allogeneic antigens in the periphery. Although the function of Treg cells has been demonstrated in many experimental settings, the precise mechanisms and antigen specificity often remain unclear. In a hepatitis B e antigen-T-cell receptor (HBeAg-TCR) double transgenic mouse model, we observed a phenotypically unique (TCR+) CD4- /CD8- CD25(+/-) GITR(high) PD-1(high) FoxP3-) HBeAg-specific population that demonstrates immune regulatory function. This HBeAg-specific double-negative regulatory cell population proliferates vigorously in vitro, in contrast to any other known regulatory population, in an interleukin-2-independent manner. PMID- 22044158 TI - Rational identification of enoxacin as a novel V-ATPase-directed osteoclast inhibitor. AB - Binding between vacuolar H+-ATPases (V-ATPases) and microfilaments is mediated by an actin binding domain in the B-subunit. Both isoforms of mammalian B-subunit bind microfilaments with high affinity. A similar actinbinding activity has been demonstrated in the B-subunit of yeast. A conserved "profilin-like" domain in the B-subunit mediates this actin-binding activity, named due to its sequence and structural similarity to an actin-binding surface of the canonical actin binding protein profilin. Subtle mutations in the "profilin-like" domain eliminate actin binding activity without disrupting the ability of the altered protein to associate with the other subunits of V-ATPase to form a functional proton pump. Analysis of these mutated B-subunits suggests that the actin-binding activity is not required for the "housekeeping" functions of V-ATPases, but is important for certain specialized roles. In osteoclasts, the actin-binding activity is required for transport of V-ATPases to the plasma membrane, a prerequisite for bone resorption. A virtual screen led to the identification of enoxacin as a small molecule that bound to the actin-binding surface of the B2-subunit and competitively inhibited B2-subunit and actin interaction. Enoxacin disrupted osteoclastic bone resorption in vitro, but did not affect osteoblast formation or mineralization. Recently, enoxacin was identified as an inhibitor of the virulence of Candida albicans and more importantly of cancer growth and metastasis. Efforts are underway to determine the mechanisms by which enoxacin and other small molecule inhibitors of B2 and microfilament binding interaction selectively block bone resorption, the virulence of Candida, cancer growth, and metastasis. PMID- 22044160 TI - CD11d Antibody Treatment Improves Recovery in Spinal Cord-Injured Mice. AB - Acute administration of a monoclonal antibody (mAb) raised against the CD11d subunit of the leukocyte CD11d/CD18 integrin after spinal cord injury (SCI) in the rat greatly improves neurological outcomes. This has been chiefly attributed to the reduced infiltration of neutrophils into the injured spinal cord in treated rats. More recently, treating spinal cord-injured mice with a Ly-6G neutrophil-depleting antibody was demonstrated to impair neurological recovery. These disparate results could be due to different mechanisms of action utilized by the two antibodies, or due to differences in the inflammatory responses between mouse and rat that are triggered by SCI. To address whether the anti CD11d treatment would be effective in mice, a CD11d mAb (205C) or a control mAb (1B7) was administered intravenously at 2, 24, and 48 h after an 8-g clip compression injury at the fourth thoracic spinal segment. The anti-CD11d treatment reduced neutrophil infiltration into the injured mouse spinal cord and was associated with increased white matter sparing and reductions in myeloperoxidase (MPO) activity, reactive oxygen species, lipid peroxidation, and scar formation. These improvements in the injured spinal cord microenvironment were accompanied by increased serotonin (5-HT) immunoreactivity below the level of the lesion and improved locomotor recovery. Our results with the 205C CD11d mAb treatment complement previous work using this anti-integrin treatment in a rat model of SCI. PMID- 22044161 TI - Mean exposure fractions of human body solar UV exposure patterns for application in different ambient climates. AB - In this research, the erythemally effective UV measured using miniaturized polysulphone dosimeters to over 1250 individual body sites and collected over a 4 year period is presented relative to the total exposed skin surface area (SSA) of a life-size manikin model. A new term is also introduced, the mean exposure fraction (MEF). The MEF is used to weight modeled or measured horizontal plane UV exposures to the total unprotected SSA of an individual and is defined as the ratio of exposure per unit area received by the unprotected skin surfaces of the body relative to the exposure received on a horizontal plane. The MEF has been calculated for a range of solar zenith angles (SZA) to provide a sunburning energy data set weighted to the actual SSA of a typically clothed individual. For this research, the MEF was determined as 0.15, 0.26 and 0.41 in the SZA ranges 0 degrees -30 degrees , 30 degrees -50 degrees and 50 degrees -80 degrees providing information that can be used in a variety of different ambient, latitudinal and seasonal climates where total human body UV exposure information is not available. PMID- 22044162 TI - New in vitro tools to study human constitutive androstane receptor (CAR) biology: discovery and comparison of human CAR inverse agonists. AB - The human constitutive androstane receptor (CAR, NR1I3) is one of the key regulators of xenobiotic and endobiotic metabolism. The unique properties of human CAR, such as the high constitutive activity and the complexity of signaling, as well as the lack of functional and predictive cell-based assays to study the properties of the receptor, have hindered the discovery of selective human CAR ligands. Here we report a novel human CAR inverse agonist, 1-[(2 methylbenzofuran-3-yl)methyl]-3-(thiophen-2-ylmethyl) urea (S07662), which suppresses human CAR activity, recruits the corepressor NCoR in cell-based assays, and attenuates the phenytoin- and 6-(4-chlorophenyl)imidazo[2,1 b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO)-induced expression of CYP2B6 mRNA in human primary hepatocytes. The properties of S07662 are also compared with those of known human CAR inverse agonists by using an array of different in vitro and in silico assays. The identified compound S07662 can be used as a chemical tool to study the biological functions of human CAR and also as a starting point for the development of new drugs for various conditions involving the receptor. PMID- 22044163 TI - Theoretical studies of host-guest interaction in gas hydrates. AB - Ab initio calculations and atoms-in-molecules (AIM) analysis have been used to investigate the host-guest interaction in dodecahedral water cages using a variety of guest species that include monatomic (He, Ne, Ar, Kr, and Xe), diatomic (CO, H(2), N(2), O(2), and NO), triatomic (CO(2), NO(2), and O(3)), and polyatomic (CH(4) and NH(3)) molecules. Geometry optimization for the guest species, host cage, and their complexes was carried out using the second order Moller-Plesset perturbation method with the 6-31G** basis set. Single point energy calculations using the same method but different basis sets (6-31++G**, 6 311++G**, aug-cc-pVDZ, and aug-cc-pVTZ) were carried out for the MP2/6-31G** optimized geometries. The interaction energy between the guest species and the host cage has been obtained in the complete basis set limit by basis set extrapolation. PMID- 22044165 TI - A new xanthone from Garcinia nitida. AB - A detailed chemical study on the stem bark of Garcinia nitida has led to the isolation of five xanthones. They are 1,6-dihydroxy-5-methoxy-6,6 dimethylpyrano[2',3':2,3]-xanthone (1), inophyllin B (2), osajaxanthone (3), 3 isomangostin (4) and rubraxanthone (5). The structures of these compounds were established using mainly 1-D and 2-D NMR spectroscopy ((1)H, (13)C, DEPT, COSY, HMBC and HMQC) while molecular masses were determined via MS techniques; 1 is a new compound. PMID- 22044164 TI - Design and synthesis of 2-heterocyclyl-3-arylthio-1H-indoles as potent tubulin polymerization and cell growth inhibitors with improved metabolic stability. AB - New arylthioindoles (ATIs) were obtained by replacing the 2-alkoxycarbonyl group with a bioisosteric 5-membered heterocycle nucleus. The new ATIs 5, 8, and 10 inhibited tubulin polymerization, reduced cell growth of a panel of human transformed cell lines, and showed higher metabolic stability than the reference ester 3. These compounds induced mitotic arrest and apoptosis at a similar level as combretastatin A-4 and vinblastine and triggered caspase-3 expression in a significant fraction of cells in both p53-proficient and p53-defective cell lines. Importantly, ATIs 5, 8, and 10 were more effective than vinorelbine, vinblastine, and paclitaxel as growth inhibitors of the P-glycoprotein overexpressing cell line NCI/ADR-RES. Compound 5 was shown to have medium metabolic stability in both human and mouse liver microsomes, in contrast to the rapidly degraded reference ester 3, and a pharmacokinetic profile in the mouse characterized by a low systemic clearance and excellent oral bioavailability. PMID- 22044166 TI - Cost-effectiveness analysis of burning mouth syndrome therapy. AB - OBJECTIVE: To study the cost-effectiveness of four alternative treatments for burning mouth syndrome (BMS). METHODS: A cost-effectiveness analysis was conducted from a healthcare payer perspective of four therapy strategies (amisulpride, paroxetine, sertraline and topical clonazepam), using a decision tree model that incorporated direct healthcare costs and probabilities associated with the possible events and outcomes. Average cost-effectiveness and incremental cost-effectiveness ratios were calculated. Sensitivity analyses included the costs of brand name and generic drugs in five European countries (France, Italy, the Netherlands, Spain and UK), as well as two scenarios with different treatment length. RESULTS: Of the drugs analysed, topical clonazepam proved to be the most cost-effective therapy. Although generic proved more efficient than brand name drugs, they displayed no advantage over brand name topical clonazepam. The Netherlands was the country with the highest overall drug efficiency. Sensitivity analyses highlighted the robustness of the model, because topical clonazepam proved to be the most efficient therapy under all the different scenarios. CONCLUSIONS: Topical clonazepam, which previous analyses of clinical evidence have shown to be the drug of choice for BMS, also proved to be the most cost effective of the drugs analysed for this condition. PMID- 22044167 TI - Identification of interactions involved in the generation of nucleophilic reactivity and of catalytic competence in the catalytic site Cys/His ion pair of papain. AB - Understanding the roles of noncovalent interactions within the enzyme molecule and between enzyme and substrate or inhibitor is an essential goal of the investigation of active center chemistry and catalytic mechanism. Studies on members of the papain family of cysteine proteinases, particularly papain (EC 3.4.22.2) itself, continue to contribute to this goal. The historic role of the catalytic site Cys/His ion pair now needs to be understood within the context of multiple dynamic phenomena. Movement of Trp177 may be necessary to expose His159 to solvent with consequent decrease in its degree of electrostatic solvation of (Cys25)-S(-). Here we report an investigation of this possibility using computer modeling of quasi-transition states and pH-dependent kinetics using 3,3' dipyridazinyl disulfide, its n-propyl and phenyl derivatives, and 4,4' dipyrimidyl disulfide as reactivity probes that differ in the location of potential hydrogen-bonding acceptor atoms. Those interactions that influence ion pair geometry and thereby catalytic competence, including by transmission of the modulatory effect of a remote ionization with pK(a) 4, were identified. A key result is the correlation between the kinetic influence of the modulatory trigger of pK(a) 4 and disruption of the hydrogen bond donated by the indole N-H of Trp177, the hydrophobic shield of the initial "intimate" ion pair. This hydrogen bond is accepted by the amide O of Gln19-a component of the oxyanion hole that binds the tetrahedral species formed from the substrate during the catalytic act. The disruption would be expected to contribute to the mobility of Trp177 and possibly to the effectiveness of the binding of the developing oxyanion. PMID- 22044168 TI - The optimal forum for a vigorous, active and informed debate about service priorities and therapeutic directions. PMID- 22044169 TI - Depolarizing bipolar disorder: both the illness and our views. PMID- 22044170 TI - Risk, disorder and diagnosis. PMID- 22044171 TI - Translational medicine: a new creed? PMID- 22044172 TI - The emerging use of brain stimulation treatments for psychiatric disorders. AB - OBJECTIVE: The aim of this study was to review the current state of development and application of a wide range of brain stimulation approaches in the treatment of psychiatric disorders. METHOD: The approaches reviewed include forms of minimally invasive magnetic and electrical stimulation, seizure induction, implanted devices and several highly novel approaches in early development. RESULTS: An extensive range of brain stimulation approaches are now being widely used in the treatment of patients with psychiatric disorders, or actively investigated for this use. Both vagal nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) have been introduced into clinical practice in some countries. A small body of research suggests that VNS has some potentially long-lasting antidepressant effects in a minority of patients treated. rTMS has now been extensively investigated for over 15 years, with a large body of research now supporting its antidepressant effects. Further rTMS research needs to focus on defining the most appropriate stimulation methods and exploring its longer term use in maintenance protocols. Very early data suggest that magnetic seizure therapy (MST) has promise in the treatment of patients referred for electroconvulsive therapy: MST appears to have fewer side effects and may have similar efficacy. A number of other approaches including surgical and alternative forms of electrical stimulation appear to alter brain activity in a promising manner, but are in need of evaluation in more substantive patient samples. CONCLUSIONS: It appears likely that the range of psychiatric treatments available for patients will grow over the coming years to progressively include a number of novel brain stimulation techniques. PMID- 22044173 TI - Epidemiology of anxiety disorders in the Australian general population: findings of the 2007 Australian National Survey of Mental Health and Wellbeing. AB - OBJECTIVE: The aims of this study were to report 12-month and lifetime prevalence for anxiety disorders in the Australian general population, identify sociodemographic and clinical correlates of anxiety disorders, and report the rates of comorbidity among anxiety, affective, and substance use disorders across the lifespan. METHOD: The 2007 National Survey of Mental Health and Wellbeing was a nationally representative, face-to-face household survey of 8841 (60% response rate) community residents aged between 16 and 85 years. Diagnoses for anxiety, affective and substance use disorders were made according to the DSM-IV using the World Mental Health Survey Initiative version of the Composite International Diagnostic Interview. RESULTS: 12-month and lifetime prevalence of anxiety disorders were 11.8% and 20.0%, respectively. Anxiety disorders had a similar median age of onset (19 years) compared to substance use disorders (20 years), but earlier than affective disorders (34 years). Social phobia was the earliest onset anxiety disorder (median 13 years), with generalized anxiety disorder the latest (median 33 years). Significant correlates of the presence of anxiety disorders included being female, single, not in the labour force, in the middle age groups, not having post-graduate qualifications, having a comorbid physical condition, and having a family history of mental disorders. Being in the oldest age ranges and being born in another non-English speaking country were associated with lower odds of having an anxiety disorder. Body mass index was not associated with the presence of an anxiety disorder. Anxiety disorders were highly comorbid, particularly with major depression, dysthymia, and alcohol dependence. Comorbidity with substance use disorders reduced with age. Comorbidity with affective disorders was high across the lifespan. CONCLUSIONS: Anxiety disorders are common, can have an early onset, and are highly comorbid. Prevention, early detection, and treatment of anxiety disorders should be a priority. PMID- 22044175 TI - Backscattered electron detection in environmental SEM. AB - An examination of the backscattered electron imaging status in environmental scanning electron microscopy is presented with particular attention to the testing and use of cerium doped yttrium aluminium garnet and yttrium aluminium perovskite scintillation detectors. A comparison is made with plastic scintillating backscattered electron detectors used previously (Nuclear Enterprises type NE102A scintillator). Semi-disk, strip and wedge shapes of these materials have been tested in conjunction with various light-guide geometries. These systems have been combined with two different types of photomultipliers, which also play a critical role in the total detector efficiency. The advantage of increased light output from the monocrystal materials is gained only if matched with suitable light-guides and photomultipliers. The associated problems are discussed and proposals for further work are made for the construction of most efficient backscattered electron detectors in the environmental scanning electron microscope. PMID- 22044176 TI - The effect of curing conditions on the physical properties of tricalcium silicate cement for use as a dental biomaterial. AB - AIM: To investigate the physical properties of tricalcium silicate (TCS) with and without the addition of a radiopacifier and compare them with that of Portland cement (PC) and radiopaque PC in an mineral trioxide aggregate-like system. METHODOLOGY: Tricalcium silicate, PC and radiopacified variants containing 20% bismuth oxide were tested for radiopacity, compressive strength, setting time and dimensional stability. All the testing was performed at 37 degrees C and under different environmental conditions namely at 100% humidity or immersed in either water or Hank's balanced salt solution (HBSS). Testing was performed after both 1 and 28 days. RESULTS: The cements exhibited radiopacity values equivalent to <3 mm. Addition of 20% bismuth oxide resulted in adequate radiopacity. The strength of TCS was independent of the curing conditions. The cements without radiopacifier had improved strength characteristics when immersed in HBSS, whilst the radiopacified cements exhibited higher strengths when soaked in water. Tricalcium silicate demonstrated the shortest setting time. Addition of bismuth oxide increased the setting time of the cements while HBSS inhibited the setting of bismuth oxide-replaced cements. The PC-based materials exhibited a net contraction higher than that recorded for TCS-based cements in all curing conditions. The dimensional change exhibited by the specimens was generally greater in the first few hours of setting, but then stabilized with time. CONCLUSIONS: Tricalcium silicate cement required the addition of a radiopacifying agent to make it suitable for use as a dental material. Tricalcium silicate exhibited adequate physical properties and thus was shown to be a suitable replacement for the PC component in MTA. Bismuth oxide drastically increased the setting time of the test cements in phosphate-containing solutions. Alternative radiopacifiers that do not retard the setting time need to be investigated. PMID- 22044177 TI - Reversal of hemorrhagic shock in rats using the metabolically stable thyrotropin releasing hormone analog taltirelin hydrate. AB - We investigated the effect of taltirelin hydrate ((-)-N-[(S)-hexahydro-1-methyl- 2,6-dioxo-4-pyrimidinyl-carbonyl]-L-histidyl-L-prolinamide tetrahydrate; taltirelin), a metabolically stable thyrotropin-releasing hormone (TRH) analog, on circulatory function, respiratory function, and viable time after bleeding in urethane-anesthetized rats. Massive volume-controlled bleeding caused marked reductions in mean arterial pressure (MAP) and respiratory rate (RR). The vital signs of control rats were lost within an average of 23 min after bleeding. Intravenous administration of taltirelin (0.03-0.3 mg/kg) and TRH (1 and 3 mg/kg) immediately after bleeding accelerated recovery of MAP and RR, and prolonged viable time in a dose-dependent manner. The potency of taltirelin in accelerating MAP and RR recovery and prolonging viable time was higher when compared with that of TRH. In addition, recovery of MAP and RR and the extension of viable time by taltirelin were inhibited by preintraperitoneal administration of atropine sulfate, which is a centrally acting muscarinic antagonist, but not by that of atropine methylbromide, which is a peripherally acting muscarinic antagonist. Taltirelin also recovered decreased arterial pH, bicarbonate ions, and base excess, and prevented a decrease in arterial oxygen saturation. In conclusion, the anti-shock effect of taltirelin was more potent than that of TRH. Taltirelin activity was mediated by the central muscarinic cholinergic system. In addition, taltirelin also corrected metabolic acidosis. These results suggest that taltirelin could be useful in the treatment of hypovolemic shock. PMID- 22044179 TI - Canadian and Spanish youths' risk perceptions of drinking and driving, and riding with a drunk driver. AB - The present research compared Canadian and Spanish youths' perceptions of the potential benefits and drawbacks of driving under the influence of alcohol (DUI) and riding with a drunk driver (RDD). Eighty (41 female) Canadian and 87 (71 female) Spanish undergraduates completed a survey asking about their past and forecasted engagement in DUI and RDD, and their perceptions of the benefits and drawbacks of DUI and RDD. A sizeable proportion of both samples reported DUI and RDD in the past year. Past risk takers forecasted significantly greater chances of engaging in these behaviors in the following year compared to those who had not engaged in DUI and RDD. Both samples provided significantly more drawbacks than benefits of DUI and RDD. Whereas the benefits of both behaviors tended to refer to personal effects (e.g., save money, arrive faster) that occurred before, during, or after driving, the drawbacks referred to a range of outcomes (e.g., accident, kill/injure, penal sanction) that mostly occurred during driving. Although Canada and Spain differ in important respects (e.g., potential penalty for DUI), there were similarities in the two samples' perceptions of DUI and RDD. Young people are aware of the costs of these risky behaviors but nevertheless engage in them. These findings can inform theories of the co-occurrence of risky driving behaviors, and the development of prevention programs that focus on perceived outcomes. PMID- 22044180 TI - Assortative mating in morningness-eveningness. AB - Individuals differ in their morningness-eveningness preference (circadian preference); that is, some prefer morning hours for intellectual and physical activities and others prefer late afternoon or evening hours. This has been viewed as an interesting facet of personality. Assortative mating has been studied in personality research, but assortative mating in circadian preference has rarely been examined. Eighty-four couples participated in this study. They filled in the Composite Scale of Morningness; they also supplied data about rise times and bedtimes as well as information about relationship satisfaction and duration. The results revealed a moderate positive relationship between couple partners in morningness-eveningness which persisted after correcting for age. Similarly, correlations existed between the sleep-wake variables (rise time and bedtime) on weekdays and on the weekends, the association being higher for weekends. There was no significant correlation between length of the relationship and dissimilarity in morningness-eveningness, suggesting that the above-reported correlations reflect an initial assortment rather than convergence effects. Further, no significant correlation was found between dissimilarity in morningness-eveningness and relationship satisfaction. The results suggest that assortative mating in morningness-eveningness is likely and is probably based on an initial assortment. The likelihood to meet and mate may also be linked to chronotype. When differences in circadian preferences exist between possible partners, this reduces the likelihood that these persons meet either by accident or during work and leisure activities. Therefore, two extreme chronotypes are unlikely to meet each other because they have the smallest overlap in their preferred active time during the day due to the circadian rhythmicity. PMID- 22044181 TI - Who finds neutral pictures pleasant and relaxing? AB - Valence and arousal are independent dimensions of consciously experienced affect. The former refers to pleasantness; the latter to the degree of excitement or stimulation. The present research explores some of the predictors of these dimensions through the hypothesis that valence relates to positive affect and lack of negative affect, while arousal is tied to negative affect, and that both are predicted by personal wellbeing, considered as a way of achieving happiness. The occurrence of depressive symptoms is also considered within the hypothesis: as a facet of negative affect, as lack of wellbeing, or as an independent dimension placed at the same level as wellbeing, and which relates to both positive and negative affect (considered as mediators). Sixty-one participants were asked to view on a computer screen a series of 20 neutral pictures, having medium valence and low arousal, and complete self-report questionnaires to assess affect, personal wellbeing, and the occurrence of depressive symptoms. After picture viewing, valence and arousal judgments were requested. In the analysis, three competing models with latent variables were tested, to assess at best the role depressive symptoms have. They confirmed that valence is predicted by high positive and low negative affect, arousal by negative affect and even directly by the occurrence of depressive symptoms, and that personal wellbeing and depressive symptoms are the starting point. They are negatively correlated and predict positive (both) and negative affect (just the occurrence of depressive symptoms). The discussion focuses on both theoretical and practical implications. Suggestions for future research are given. PMID- 22044182 TI - Psychological wellbeing of Turkish university students with physical impairments: an evaluation within the stress-vulnerability paradigm. AB - Generally, universities in developing countries offer little in the way of provisions and support (material, emotional, etc.) for disabled students. Therefore, disabled students experience considerable burdens and barriers in their educational life. This study investigated the psychological wellbeing of disabled Turkish university students by examining influences on stress-related growth and psychological distress. Disability is defined within the framework of a social model. According to this view, impairment refers to the functional limitation(s) that affect(s) a person's body, whereas disability refers to the loss or limitation of opportunities owing to social, physical or psychological obstacles. Seventy disabled university students with physical impairments were administered a questionnaire package, including a sociodemographic information sheet, Ways of Coping Questionnaire, Stress-Related Growth Scale, Multidimensional Scale of Social Support, Life Events Inventory, and Brief Symptom Inventory. Snowball sampling was used and voluntary participation was essential. The results showed that disability burden, daily hassles, and helplessness coping were significant predictors of psychological symptoms. For stress-related growth the only variable that appeared significant was problem solving coping. The results pointed out that there may be different pathways to distress and growth. In order to decrease psychological distress and enhance growth in disabled university students, disability awareness programs, changes in the barriers in the academic and physical environments of the university campuses, and coping skills training to increase problem-focused coping and to combat helplessness may prove to be effective. Reducing daily hassles for the disabled students is likely to contribute to their wellbeing by decreasing their burdens. Also, a more disability-friendly environment is likely to be empowering for disabled university students. PMID- 22044183 TI - Hemispheric asymmetry in recognition memory: effects of retention level on the recognition of Portuguese words. AB - Early findings from Broca and Wernicke led to the classical view of hemispheric specialization, where the main idea relates to left-hemisphere language capabilities compared to right-hemisphere visual capabilities. Federmeier and Benjamin (2005) have suggested that semantic encoding for verbal information in the right hemisphere can be more effective when memory demands are higher. In light of this, our main goal was to study the effect of retention level of verbal information on hemispheric processes. However, regarding the cross-linguistic differences in orthography and their subsequent effects on word recognition (Frost, Katz, & Bentin, 1987), our intent was also to test prior predictions of Federmeier and Benjamin (2005) for a "shallow" orthography language, where words have a clear correspondence between graphemes and phonemes, as opposed to English, which is a "deep" orthography language. Portuguese concrete nouns were selected. The participants were submitted to a visual half-field word presentation using a continuous recognition memory paradigm. The retention level included 1, 2, 4, 8, 20 or 40 words. Results showed that recognition accuracy was higher for words studied in the right visual field, compared to those studied in the left visual field, when the retention interval included 2, 4, or 20 words. No significant differences were found for the remaining intervals. Further analysis on accuracy data for intermediate retention levels showed that recognition accuracy was higher for the 2 words retention level than for the levels including 4, 8, or 20 words; it was higher for left-hemisphere encoding as well. Our results also indicated that reaction times were slower for left-hemisphere encoding and for the 40 words retention level when compared to that of 20 words. In summary, the current results are in partial agreement with those of Federmeier and Benjamin (2005) and suggest different hemispheric memory strategies for the semantic encoding of verbal information. PMID- 22044184 TI - Coping with traumatic stress in journalism: a critical ethnographic study. AB - Journalists who witness trauma and disaster events are at risk for physical, emotional, and psychological injury. The purpose of this paper is to present the results of a critical ethnographic study among 31 Canadian journalists and photojournalists with regard to coping strategies used to buffer the effects of being exposed to trauma and disaster events and work-related stress. The findings are the result of in-depth individual interviews and six workplace observations with journalists across Canada. The most commonly reported coping strategies were: avoidance strategies at work, use of black humor, controlling one's emotions and memories, exercise and other physical activities, focusing on the technical aspects, and using substances. Recommendations for addressing the effects of work-related stress within this population are provided. PMID- 22044185 TI - Cultural context, obsessive-compulsive disorder symptoms, and cognitions: a preliminary study of three Turkish samples living in different countries. AB - Previous research findings have suggested that recent cognitive accounts of obsessive-compulsive disorder (OCD) are valid across different cultural contexts for both clinical and nonclinical samples; however, there is evidence that cultural differences may have an impact on a number of cognitive variables. For this reason, immigration provides an exceptional opportunity for an examination of the role of cultural context in cognitions and possible changes in cultural characteristics. To this end, the present study examined the interrelationships between thought-action fusion, thought control strategies and OCD symptoms in three nonclinical samples, taking the immigration factor into consideration. Thus, the current study included three Turkish sample groups: those who remigrated to Turkey from Bulgaria, those still living in Bulgaria, and those that have always resided in Turkey. The findings of the study supported the role of thought and action fusion and control strategies in OCD symptoms in a cross cultural context. To illustrate, worry, as a thought control strategy for OCD symptoms, was a common factor in all three sample groups. However, differences were also noted between the groups, despite having the same ethnic origin. Although they immigrated back to Turkey and have been living there for a considerable period of time, the Turkish remigrants retained similar characteristics to the respondents in Bulgaria on cognitions in general. Consequently, it may be suggested that cultural context might have a relative impact on certain correlates. A replication of these findings using different immigration groups and examining various cultural factors is strongly encouraged. PMID- 22044186 TI - One-year follow-up analysis of cognitive and psychological consequences among survivors of the Wenchuan earthquake. AB - The catastrophic Wenchuan earthquake measuring 8.0 on the Richter scale occurred on May 12, 2008 in the West of the Sichuan basin in China and caused severe damage. A project was undertaken to examine the cognitive and psychological effects one year after the disaster among 2080 individuals in the local area. We evaluated the influence of gender, age, education level, and ethnic group on five aspects: work satisfaction, living satisfaction, health self-perception, psychological pressure, and psychological recovery. Male subjects had a better performance in all five aspects, which indicated that women were more affected. Subjects of different ethnic groups showed significantly different attitudes with respect to psychological pressure and psychological recovery. Significant differences for all the five aspects were also found in education level and age. The results showed that older people and those with a lower education level probably had more psychological problems. There were significant correlations between work satisfaction and living satisfaction, living satisfaction and health self-perception, living satisfaction and psychological recovery, and psychological pressure and psychosocial recovery. Living satisfaction and education level were significant predictors of psychological pressure. For psychological recovery, significant predictors were living satisfaction, age, work satisfaction, education level, and gender. The study findings indicated that government programs should provide more support for females, older people, those with a lower education level, and those in lower living conditions. Attention should be given not only to the psychological effects on each victim, but also to related issues such as work and living conditions to promote psychological wellbeing. Limitations of this study are addressed. PMID- 22044188 TI - Intercomparison of thermal-optical methods for the determination of organic and elemental carbon: influences of aerosol composition and implications. AB - An intercomparison of organic carbon (OC) and elemental carbon (EC) measurements was conducted based on ambient aerosol samples collected during four seasons in Beijing, China. Dependence of OC and EC values on the temperature protocol and the charring correction method is presented and influences of aerosol composition are investigated. EC was found to decrease with the peak inert mode temperature (T(peak)) such that EC determined by the IMPROVE (the Interagency Monitoring of Protected Visual Environments)-A protocol (T(peak) was 580 degrees C) was 2.85 +/- 1.31 and 3.83 +/- 2.58 times that measured by an alternative protocol with a T(peak) of 850 degrees C when using the transmittance and reflectance correction, respectively. It was also found that reflectance correction tends to classify more carbon as EC compared with transmittance; results from the IMPROVE A protocol showed that the ratio of EC defined by reflectance correction (EC(R)) to that based on transmittance (EC(T)) averaged 1.50 +/- 0.42. Moreover, it was demonstrated that emissions from biomass burning would increase the discrepancy between EC values determined by different temperature protocols. On the other hand, the discrepancy between EC(R) and EC(T) was strongly associated with secondary organic aerosol (SOA) which was shown to be an important source of the organics that pyrolyze during the inert mode of thermal-optical analysis. PMID- 22044189 TI - Short- and long-term effects of juvenile stressor exposure on the expression of GABAA receptor subunits in rats. AB - During the juvenile period rodents are particularly sensitive to stressors. Aversive events encountered during this period may have enduring effects that are not evident among animals initially stressed as adults. Interestingly, experiencing stressor during juvenile period was found to elicit a biphasic behavioral pattern over the course of development. During the juvenile period, the expression of several GABAA receptor subunits is subject to elevated plasticity, rendering the GABAergic system sensitive to stressors. In the present investigation, animals were exposed to a juvenile variable stressor regimen (JUV S) at 27-29 postnatal days (PND): 27 PND-acute swim stress (10 min), 28 PND elevated platform stress (3 sessions*30 min each), and 29 PND-restraint (2 h). One hour following the last exposure to stressor or in adulthood (60 PND), anxiety-related behaviors were assessed in a 5-min elevated plus maze test. The western blotting technique was used to evaluate whether the juvenile stress induced behavioral pattern will be accompanied by respective changes in GABAA alpha1, alpha2, and alpha3 protein expression in male rats. Our findings further established that juvenile stressor elicits hyper-reactivity when rats were tested as juveniles, whereas rats exhibited reduced activity and increased anxiety when tested as adults. Additionally, the effects of juvenile stressor on alpha1, alpha2, and alpha3 were more pronounced among juvenile stressed rats that were challenged as adults compared with rats that were only challenged as juveniles. Interestingly, the stress-induced modulation of the subunits was particularly evident in the amygdala, a brain region closely associated with anxiety. Thus, age- and region-specific alterations of the alpha subunits may contribute to the age-specific behavioral alterations observed following juvenile stress exposure. PMID- 22044191 TI - MHC class I dimer formation by alteration of the cellular redox environment and induction of apoptosis. AB - Many MHC class I molecules contain unpaired cysteine residues in their cytoplasmic tail domains, the function of which remains relatively uncharacterized. Recently, it has been shown that in the small secretory vesicles known as exosomes, fully folded MHC class I dimers can form through a disulphide bond between the cytoplasmic tail domain cysteines, induced by the low levels of glutathione in these extracellular vesicles. Here we address whether similar MHC class I dimers form in whole cells by alteration of the redox environment. Treatment of the HLA-B27-expressing Epstein-Barr virus-transformed B-cell line Jesthom, and the leukaemic T-cell line CEM transfected with HLA-B27 with the strong oxidant diamide, and the apoptosis-inducing and glutathione-depleting agents hydrogen peroxide and thimerosal, induced MHC class I dimers. Furthermore, induction of apoptosis by cross-linking FasR/CD95 on CEM cells with monoclonal antibody CH-11 also induced MHC class I dimers. As with exosomal MHC class I dimers, the formation of these structures on cells is controlled by the cysteine at position 325 in the cytoplasmic tail domain of HLA-B27. Therefore, the redox environment of cells intimately controls induction of MHC class I dimers, the formation of which may provide novel structures for recognition by the immune system. PMID- 22044190 TI - Glycine, a simple physiological compound protecting by yet puzzling mechanism(s) against ischaemia-reperfusion injury: current knowledge. AB - Ischaemia is amongst the leading causes of death. Despite this importance, there are only a few therapeutic approaches to protect from ischaemia-reperfusion injury (IRI). In experimental studies, the amino acid glycine effectively protected from IRI. In the prevention of IRI by glycine in cells and isolated perfused or cold-stored organs (tissues), direct cytoprotection plays a crucial role, most likely by prevention of the formation of pathological plasma membrane pores. Under in vivo conditions, the mechanism of protection by glycine is less clear, partly due to the physiological presence of the amino acid. Here, inhibition of the inflammatory response in the injured tissue is considered to contribute decisively to the glycine-induced reduction of IRI. However, attenuation of IRI recently achieved in experimental animals by low-dose glycine treatment regimens suggests additional/other (unknown) protective mechanisms. Despite the convincing experimental evidence and the large therapeutic width of glycine, there are only a few clinical trials on the protection from IRI by glycine with ambivalent results. Thus, both the mechanism(s) behind the protection of glycine against IRI in vivo and its true clinical potential remain to be addressed in future experimental studies/clinical trials. PMID- 22044192 TI - PPAD: a tool for presumption of atopic dermatitis. AB - Although it is a frequent disease, atopic dermatitis is poorly recognised and therefore under-diagnosed. The aim of this study was to define and validate a convenient tool allowing presumption of atopic dermatitis for non-dermatologists. A 20-item questionnaire (PPAD) and an 8-item short version (PPAD-S) were developed in French by a board of experts, then tested on outpatients presenting with atopic dermatitis or not. Diagnosis was confirmed by a dermatologist, who measured the severity of the disease by using SCORAD. PPAD and PPAD-S proved to be efficient tools for presumption of atopic dermatitis, but not tools for diagnosis. Scores were correlated to the severity of the disease. PPAD and PPAD-S can be considered useful tools for orientating patients with undiagnosed atopic dermatitis to a specialised consultation, all the more quickly since atopic dermatitis is severe. PMID- 22044193 TI - Hydration of proteins: excess partial enthalpies of water and proteins. AB - Isothermal batch calorimetry was applied to study the hydration of proteins. The hydration process was analyzed by the simultaneous monitoring of the excess partial enthalpies of water and the proteins in the entire range of water content. Four unrelated proteins (lysozyme, chymotrypsinogen A, human serum albumin, and beta-lactoglobulin) were used as models. The excess partial quantities are very sensitive to the changes in the state of water and proteins. At the lowest water weight fractions (w(1)), the changes of the excess thermochemical functions can mainly be attributed to water addition. A transition from the glassy to the flexible state of the proteins is accompanied by significant changes in the excess partial quantities of water and the proteins. This transition appears at a water weight fraction of 0.06 when charged groups of proteins are covered. Excess partial quantities reach their fully hydrated values at w(1) > 0.5 when coverage of both polar and weakly interacting surface elements is complete. At the highest water contents, water addition has no significant effect on the excess thermochemical quantities. At w(1) > 0.5, changes in the excess functions can solely be attributed to changes in the state of the proteins. PMID- 22044194 TI - Magnetic drug targeting in a rhabdomyosarcoma rat model using magnetite-dextran composite nanoparticle-bound mitoxantrone and 0.6 tesla extracorporeal magnets - sarcoma treatment in progress. AB - BACKGROUND: Magnetic drug targeting (MDT) is a new treatment principle for tumors. Passive MDT (pMDT) uses cytostatics coupled to ferromagnetic nanoparticles, whereas in active MDT (aMDT), extracorporeal magnets are additionally placed over the tumor area. PURPOSE: Mitoxantrone-magnetite-dextran composite particles were used to assess the distribution and effect of MDT. METHODS: We conducted two trials with n = 60 rats transfected with R(1)H rhabdomyosarcoma cells. In the biodistribution trial (n = 36) mitoxantrone concentrations in tumor tissue versus plasma were measured after one or two dose administration for aMDT, pMDT, and uncoupled mitoxantrone. The dose/effect trial (n = 24) assessed change in tumor volume at day 1 and 7 days after administration of 4, 6, or 8 doses of mitoxantrone using aMDT. RESULTS: Mitoxantrone-magnetite dextran concentration in blood was significantly (p < 0.05) lower when using aMDT and as low as uncoupled mitoxantrone. Concentrations in tumor tissue were always significantly higher using MDT when compared to uncoupled mitoxantrone. Two doses resulted in drug accumulation inside the tumor. Tumor growth was significantly decreased with four doses using aMDT versus no treatment. Tumor size on day 8 versus day 1 was significantly (p < 0.05) reduced after administration of six doses of mitoxantrone-magnetite-dextran. No allergies/toxic reactions were observed. CONCLUSIONS: The MDT achieves higher levels of cytostatics in tumor tissue without increased systemic concentrations and succeeds in reducing tumor volume. PMID- 22044195 TI - Effect of pomegranate seed oil on serum TNF-alpha level in dyslipidemic patients. AB - Pomegranate punicic acid and pomegranate fruit extracts have the potential effects in inhibiting tumour necrosis factor-alpha (TNF-alpha) and inflammatory diseases. The aim of this study was to evaluate the effect of pomegranate seed oil (PSO) consumption on serum TNF-alpha level in dyslipidemic patients. Fifty one subjects with serum total cholesterol concentration >200 mg/dl and serum triglyceride concentrations >150 mg/dl were randomly assigned into the PSO (n = 25) and placebo (n = 26) groups. Subjects were given 400 mg PSO or placebo capsules twice daily for 4 weeks. Six patients were excluded because of complications or lack of compliance. Serum TNF-alpha level was measured at baseline and after 4 weeks. Mean (SD) serum concentration of TNF-alpha decreased from 14.73 +/- 5.25 to 13.28 +/- 3.79 pg/ml in the PSO group (P = NS). Corresponding values in the placebo group were 12.46 +/- 1.67 versus 13.14 +/- 1.67 pg/ml (P = NS). In conclusion, administration of PSO in dyslipidemic patients does not affect the serum TNF-alpha. PMID- 22044196 TI - Protective effects of zinc, pentoxifylline, and N-acetylcysteine in an animal model of laparoscopy-induced ischemia/reperfusion injury of the small intestine. AB - BACKGROUND: Pneumoperitoneum induced to facilitate laparoscopy is associated with splanchnic hypoperfusion, ischemia/reperfusion (I/R) injury, and oxidative stress. AIM: This study investigated the effects of pre- and postlaparoscopic conditioning, zinc, pentoxifylline, and N-acetylcysteine on markers of I/R injury of the small intestine in an animal model. METHODS: Male Sprague-Dawley rats (n=56) were randomized to 1 of 7 treatment groups. Except for group 7 (control group that underwent sham surgery without pneumoperitoneum), pneumoperitoneum was induced in all by use of carbondioxide insufflation under a pressure of 15 mmHg. Group 1 (laparoscopic I/R) was subjected to 60 minutes of pneumoperitoneum. Group 2 (laparoscopic preconditioning plus laparoscopy) was subjected to 5 minutes of insufflation and 5 minutes of desufflation followed by 60 minutes of pneumoperitoneum. Group 3 (laparoscopy plus laparoscopic postconditioning) was subjected to 60 minutes of pneumoperitoneum and 60 minutes of desufflation followed by 5 minutes of insufflation and 5 minutes of desufflation. Group 4 (zinc), group 5 (pentoxifylline), and group 6 (N-acetylcysteine) received a single intraperitoneal injection of zinc (50 mg/kg), pentoxifylline (50 mg/kg), or N-acetylcysteine (150 mg/kg), respectively, 5 minutes before the desufflation period. Animals were killed at the end of the experiments, and small intestine samples were tested for malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). RESULTS: There was no significant difference for MDA levels between each other in the groups 1, 2, and 3. But MDA levels were higher significantly in groups 1, 2, and 3 than those of groups 4, 5, 6, and 7. SOD and GPX levels of group 3 were significantly higher than those of groups 1, 2, 4 through 7. According to the SOD levels, there was no significant difference between each other in those of groups 1, 2, 4 through 7. GPX levels of group 3 were significantly higher than those of groups 1, 2, 4 through 7. GPX levels of group 1 were significantly lower than those of groups 5 and 7. The mean CAT level of groups 1 and 2 was significantly lower than that of groups 3, 6, and 7. The mean CAT level of group 3 was significantly higher than that of groups 1, 2, 4 through 7. CONCLUSIONS: In this animal model of small intestine I/R injury, laparoscopy caused small intestine ischemia as evidenced by elevated markers of tissue I/R injury. This effect was significantly attenuated by zinc, pentoxifylline, and N-acetylcysteine, but not by prelaparoscopy conditioning and postlaparoscopy conditioning. PMID- 22044197 TI - Clinical implications of the 5alpha-androstanedione pathway for castration resistant prostate cancer. PMID- 22044199 TI - Axitinib in the treatment of metastatic renal cell carcinoma. AB - Axitinib, an oral small-molecule tyrosine kinase inhibitor targeted to angiogenesis, has demonstrated activity in advanced renal cell carcinoma. Common side effects include hypertension, fatigue and dysphonia. Axitinib is currently awaiting approval as a second-line agent in the treatment of advanced renal cell carcinoma. Trials, which include treatment-naive patients, are ongoing and will study the benefit of axitinib in the first-line setting. PMID- 22044200 TI - Ipilimumab: showing survival benefit in metastatic melanoma. AB - Ipilimumab is a fully humanized monoclonal antibody to cytotoxic T-lymphocyte associated antigen 4. Data from preclinical and clinical studies have shown that ipilimumab can cause tumor regression in patients with metastatic melanoma with response rates of 5.8-22%. Phase III trials have demonstrated a benefit in median overall survival in the first-line setting in combination with dacarbazine versus dacarbazine alone (11.2 vs 9.1 months) and in the second-line setting in combination with gp100 versus gp100 alone (10.1 vs 6.4 months). The main toxicities of ipilimumab are immune related, most commonly skin and gastrointestinal. Bowel perforation and treatment-related deaths have occurred, although prompt use of steroids and other immunosuppressive agents can minimize this risk. PMID- 22044201 TI - Incidence and prognosis of synchronous colorectal carcinomatosis: evolution since 1985? AB - Evaluation of: Lemmens VE, Klaver YL, Verwaal VJ, Rutten HJ, Coebergh JW, de Hingh IH. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int. J. Cancer 128, 2717-2725 (2011). Until recently, colorectal peritoneal carcinomatosis was considered inaccessible to curative therapy, hence the paucity of epidemiological and clinical features available to date regarding the disease. In this retrospective study, spanning 1995-2008, approximately 5% of the patients with colorectal cancer, recorded in the cancer registry of southern Netherlands, had synchronous carcinomatosis, confined to the peritoneum in nearly half of them. Despite progress in chemotherapy, surgery and anesthesiology, the survival of patients with synchronous carcinomatosis has not increased (median survival of 8 months), unlike that of patients with liver metastases. Although, only 11% of the patients had undergone complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy during the latest period (2006-2008). In the future, all patients with isolated colorectal carcinomatosis should be evaluated for curative therapy with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PMID- 22044202 TI - MRI of metastasis-permissive microenvironments. AB - One of the earliest documented observations of the importance of the microenvironment in metastasis was made by Stephen Paget in 1889. More than a century later, the metastatic cascade remains a major cause of mortality from cancer. Cancer meets the criterion of a successful organization that is able to survive by adapting to changing environments. In fact, the tumor microenvironment and stroma are co-opted and shaped by cancer cells to derive a survival advantage. Cohesive strategies integrating advances in molecular biology and chemistry, with noninvasive multimodality imaging, provide new insights into the role of the tumor microenvironment in promoting metastasis from primary tumors as well as insights into environments that attract and permit cancer cells to establish colonies in distant organs. This article provides an overview of molecular and functional imaging characterization of microenvironments that can promote or permit cancer cells to metastasize and the microenvironmental characteristics of distant metastases. PMID- 22044204 TI - Liver metastases from colorectal cancer: how to best complement medical treatment with surgical approaches. AB - Colorectal liver metastases (CLM) represent a major challenge for oncologists and surgeons. In fact, in this setting, the optimal treatment of patients can achieve a long-term survival and sometimes a definitive cure of disease. In recent years, improvements in both medical therapies and surgical approaches have led to an increased rate of patients considered amenable for surgery on CLM. New perspectives in the management of CLM underline the need for a comprehensive assessment of patient and tumor characteristics, to integrate technical and prognostic issues into an individualized therapeutic strategy in different patient subgroups. The multidisciplinary evaluation from the onset and during treatment remains the key element to maximizing the benefit of more intensive treatment modalities. PMID- 22044205 TI - Antiangiogenic effects of zoledronate on cancer neovasculature. AB - Angiogenesis, one of the hallmarks of cancer, supplies nutrients to cancerous tissues to facilitate rapid growth. Targeting cancer-associated angiogenesis is an important goal in cancer therapy and there are currently many drugs that affect tumor-associated vasculature. In this article, we will focus on the antiangiogenic effects of zoledronate (ZA), a bisphosphonate drug routinely used in the treatment of cancer-associated bone disease. This article covers the known effects of ZA throughout the clinical process. It also covers the animal models of cancer that have been treated with ZA and evaluated for angiogenes is, concluding with the current clinical data pertaining to angiogenic factors after ZA treatment. PMID- 22044203 TI - Mechanisms of cancer cell metastasis to the bone: a multistep process. AB - For metastasis to occur, tumor cells must first detach from their tissue of origin. This requires altering both the tissue of origin and the cancer cell. Once detached, cancer cells in circulation must also acquire survival mechanisms. Although many may successfully disseminate, variation exists in the efficiency with which circulating tumor cells home to and invade the bone marrow as metastastic seeds. Disseminated tumor cells that do successfully invade the marrow are secured by cell-cell and cell-extracellular matrix adhesion. However, establishing a foothold in the marrow is not sufficient for disseminated tumor cells to create metastases. A significant latent phase must be overcome by either rescuing cellular proliferation or attenuating micrometastatic mass dormancy programs. Finally, growing metastases fuel osteolysis, osteoblastogenesis and T cell differentiation, creating a variety of tumor phenotypes. Each step in the metastatic cascade is rich in biological targets and mechanistic pathways. PMID- 22044207 TI - Nanoscale delivery systems for multiple drug combinations in cancer. AB - Although drug-delivery systems have been developed to improve drug biodistribution and efficiency in cancer therapy, some limitations still hinder successful drug targeting and delivery. Multiple drugs in combination seems a promising strategy for cancer therapy. It enables drugs to be delivered to multiple targets and exhibits the additive or synergistic effects of drugs. Physiological barriers are known to be the main obstacles of insufficient drug efficacy and delivery in tumors, but they are likely to be potential targets in combination therapy as well. This article discusses some general considerations for optimizing multiply drug delivery, including drug-release profiles and loading strategies. PMID- 22044206 TI - DNA damage response and repair: insights into strategies for radiation sensitization of gliomas. AB - The incorporation of radiotherapy into multimodality treatment plans has led to significant improvements in glioma patient survival. However, local recurrence from glioma resistance to ionizing radiation remains a therapeutic challenge. The tumoricidal effect of radiation therapy is largely attributed to the induction of dsDNA breaks (DSBs). In the past decade, there have been tremendous strides in understanding the molecular mechanisms underlying DSB repair. The identification of gene products required for DSB repair has provided novel therapeutic targets. Recent studies revealed that many US FDA-approved cancer agents inhibit DSB repair by interacting with repair proteins. This article will aim to provide discussion of DSB repair mechanisms to provide molecular targets for radiation sensitization of gliomas and a discussion of FDA-approved cancer therapies that modulate DSB repair to highlight opportunities for combination therapy with radiotherapy for glioma therapy. PMID- 22044209 TI - Resorcinol-sn-glycerol derivatives: novel 2-arachidonoylglycerol mimetics endowed with high affinity and selectivity for cannabinoid type 1 receptor. AB - Since the discovery of the endocannabinoid system, evidence has been progressively accumulating to suggest that 2-arachidonoylglycerol (2-AG) rather than anandamide (AEA) is the endogenous ligand for both cannabinoid (CB) receptors. Moreover, other studies have shown that another lipid molecule, 2 arachidonyl-glycerol ether (2-AGE, noladin ether), which acts as a full agonist at cannabinoid receptors, might occur in tissues. Having previously designed a resorcinol-AEA hybrid model, in this paper we have explored the cannabinoid receptor binding properties, the CB1 functional activity, and the stability to plasma esterases of a novel series of compounds characterized by the conversion of the amide head into the glycerol-ester or glycerol-ether head, typical of 2-AG or the "putative" endocannabinoid 2-AGE, respectively. Glyceryl esters 39 and 41 displayed greater potency for CB1 (Ki in the nanomolar range) than for CB2 receptors plus the potential to be exploited as useful hits for the development of novel 2-AG mimetics. PMID- 22044211 TI - A comparison of screening tools for the assessment of mild cognitive impairment: preliminary findings. AB - We report a pilot investigation into the utility of screening tools in Mild Cognitive Impairment (MCI). The Addenbrooke's Cognitive Examination-Revised (ACE R), Montreal Cognitive Assessment (MoCA) and the novel Computer-Administered Neuropsychological Screen for Mild Cognitive Impairment (CANS-MCI) were administered to 20 elderly controls and 15 MCI cases. Non-parametric Mann-Whitney U-tests showed significant differences between groups (p < .0001) on the CANS-MCI and MoCA. The ACE-R and MoCA total scores showed high sensitivity (90%) to MCI. Area under the curve was consistently significant in discriminating controls and MCI for memory scores across all screening instruments. A useful profile of quantitative and qualitative information pertaining to cognitive functioning in MCI can be obtained with the MoCA, ACE-R, and CANS-MCI. PMID- 22044210 TI - gammadelta T cells play a protective role during infection with Nippostrongylus brasiliensis by promoting goblet cell function in the small intestine. AB - The intestinal epithelium is rich in gammadelta T cells and the gut is a site of residence for a wide variety of pathogens, including nematodes. Although CD4+ T cell receptor (TCR) -alphabeta+ T helper type 2 T cells are essential for the expulsion of intestinal nematodes, little information is available on the function of gammadelta T cells in this type of infection. Here, we demonstrate two major functions of gammadelta T cells as a potently protective T-cell population against Nippostrongylus brasiliensis infection using gammadelta T-cell deficient (TCR-delta(-/-) ) mice. First, gammadelta T cells are required to initiate rapid expulsion of adult worms from the intestine and to limit egg production. Second, gammadelta T cells prevent the pathological intestinal damage associated with nematode infection, evident by increased clinical disease and more severe microscopic lesions in infected TCR-delta(-/-) mice. gammadelta T cell deficiency led to delayed goblet cell hyperplasia in association with reduced expression of phosphorylated STAT6, MUC2, Trefoil factor-3 (TFF3) and T helper type 2 cytokines including interleukin-13 (IL-13). TCR-delta(-/-) mice also produced more interferon-gamma than wild-type mice. Within the intraepithelial lymphocyte compartment, gammadelta T cells produced IL-13. Adoptive transfer of gammadelta T cells or administration of recombinant IL-13 to TCR-delta(-/-) mice successfully reduced the egg production by N. brasiliensis. Collectively, these data provide strong evidence that gammadelta T cells play an important role in controlling infection with intestinal nematodes and limiting infection-induced pathology. PMID- 22044212 TI - Host-guest chemistry in the gas phase: complex formation with 18-crown-6 enhances helicity of alanine-based peptides. AB - The gas-phase helix propensities of alanine-based polypeptides are studied with different locations of a Lys residue and host-guest interactions with 18-Crown-6 (18C6). A series of model peptides Ac-Ala(9-n)-LysH(+)-Ala(n) (n = 0, 1, 3, 5, 7, and 9) is examined alone and with 18C6 using traveling wave ion mobility mass spectrometry combined with molecular dynamics (MD) simulations. The gas-phase helices are observed from the peptides whose Lys residue is located close to the C-terminus so that the Lys exerts its capping effect on the C-terminal carbonyl groups. The peptides, which interact with 18C6 in the gas phase, show enhanced helical propensities. The enhanced helicity of the peptide in the complex is attributed by isolation of the Lys butylammonium group from the helix backbone and the interaction of methylene groups of 18C6, which possess localized positive partial charges, with C-terminal carbonyl groups serving as a cap to stabilize the helix. PMID- 22044213 TI - The future of nursing institute of medicine report: one year later. PMID- 22044214 TI - Co-providing: understanding the logistics. AB - Continuing nursing education providers have sometimes said that they don't want to co-provide because "it's too much trouble" or they "won't be able to control what happens" or because they don't understand the process. This column clarifies the logistics of the co-provider relationship. PMID- 22044215 TI - Nursing education innovation: using e-learning technology to meet learners' needs. AB - Globalization, rapid advances in health care and research, and evidence-based practice challenge organizations to meet the continuing education needs of their professional staff while functioning within the confines of economic cutbacks. This column describes an innovative way technology was used to offer asynchronous learning to all members of one organization's nursing staff. PMID- 22044216 TI - Emotional intelligence: growing your self-regard. AB - This column focuses on one of the most important competencies in emotional intelligence--self-regard. PMID- 22044218 TI - Effects of altering the Si/Ca molar ratio of a calcium silicate cement on in vitro cell attachment. AB - AIM: To examine the effects of altering the Si/Ca molar ratio (6 : 4, 5 : 5, and 4 : 6) of a quick-setting calcium silicate cement on in vitro cell attachment. METHODOLOGY: Working time and setting time of three different calcium silicate cements were measured. Alamar Blue was used for real-time and repeated monitoring of cell attachment and proliferation. The Si and Ca ion concentrations of the cell culture medium in the presence of three different calcium silicate cements seeded with MG63 cells were measured. Kinetic immunofluorescent staining of MG63 cells was performed during cell attachment and spreading. Reverse transcription polymerase chain reaction was employed to determine gene expression in MG63 cells cultured on the cements. One-way analysis of variance was used to evaluate the significance of the differences between the mean values. RESULTS: The working time (4-7 min) and setting time (17-24 min) of the cements were shortened with an increase in the Ca content of the calcium silicate powders after mixing the powder with water. In contrast, the higher the Si content in the cement, the more the MG63 cells attached to the cement at all culture time-points, accompanying by the formation of more obvious actin stress fibres. Cell proliferation and differentiation increased significantly (P < 0.05) with an increase in the Si content of the calcium silicate cements. Si ion concentration of the culture medium increased significantly (P < 0.05) with increasing cement Si content and culture time-points. CONCLUSIONS: The higher Si content cement enhanced the higher expression of cell attachment, proliferation and differentiation as compared to the lower Si content cement. PMID- 22044219 TI - Self-assessed oral health, cognitive vulnerability and dental anxiety in children: testing a mediational model. AB - OBJECTIVE: To explain the association between children's self-perceived oral health status and dental anxiety, by considering their levels of cognitive vulnerability. METHODS: Participants were 161 children (47.8% female; mean age = 11.93 years) who filled in a questionnaire comprising self-assessed oral health related status, dental treatment-related cognitive vulnerability and dental anxiety measures. Gender, age and number of decayed, missing and filled permanent teeth were controlled for. Bivariate correlations, hierarchical regression analyses and structural equation modelling were conducted to test the hypotheses. RESULTS: Subjective oral health status, cognitive vulnerability variables and dental anxiety were strongly correlated. Regression and structural models testing the mediating effects of cognitive vulnerability variables on the relationship between perceived oral health and dental anxiety were supported. CONCLUSIONS: The activation of the cognitive vulnerability schema, as a mediating variable, is a mechanism by means of which children's self-perceptions of a poor oral health might lead to dental anxiety. Both components of vulnerability analysed (threat and disgust) contribute decisively to this potential process. PMID- 22044220 TI - Identification of new natural sweet compounds in wine using centrifugal partition chromatography-gustatometry and Fourier transform mass spectrometry. AB - Sweetness contributes notably to the taste-balance of dry wines and increases during oak-barrel aging owing to the release of natural sweeteners from wood. The search for such taste-active molecules, which are sometimes present at very low concentrations in wine or other complex matrixes, requires both reliable purification tools and powerful identification techniques. Here, we report the development of an original inductive method using centrifugal partition chromatography (CPC) and sensorial analysis. This method, called CPC gustatometry, was implemented to isolate a sweet fraction with only four compounds from a complex oak wood extract. The recently developed Fourier transform mass spectrometry (FT-MS, Orbitrap analyzer) was used jointly with two dimensional nuclear magnetic resonance (2D (1)H and (13)C NMR) to obtain the structural elucidation of the purified compounds. The tandem mass spectrometry (MS/MS) spectra obtained with resonant and nonresonant fragmentation modes were compared, thus providing complementary information about the molecular structure. Two oleanane-type triterpenoids substituted with galloyl and glucosyl moieties were identified, one of which exhibits sweet properties. We term these compounds which have never been reported, Quercotriterpenoside I and II. PMID- 22044223 TI - TEM image analysis and modelling: application to boehmite nanoparticles. AB - Boehmite occurs in the form of nanoparticles. Upon drying, it can form the alumina that is common in catalyst support used in refining and petrochemicals. The topotactic transformation of boehmite alumina led to an interest in the precise shape and size of these nanoparticles which is highly linked to the catalyst activity. Boehmite nanoparticles can be observed by transmission electron microscopy. Although they are highly aggregated, the analysis of transmission electron microscopy images with a specific random model approach, here a dilution model, can give an accurate estimate of their size. To use this approach, electronic noise and diffraction artefacts on the edges of the nanoparticles have to be removed. Covariance measurements on micrographs can be performed. They can be used to fit a model. The fitting uses a novel numerical method to estimate the covariogram of grains. The model can take into account the specific orientations of the nanoparticles. The influence of noise, image filters used to remove noise and diffraction artefacts, as well as all the parameters of the model are all studied in this paper. We propose nanoparticle size estimations procedures based on both single and mixture-of-two particle models. PMID- 22044222 TI - 1-Phenylisoquinoline larvicidal activity against Culex quinquefasciatus. AB - The larvicidal potential of several dopamine 1-phenylisoquinoline derivatives against Culex quinquefasciatus third instar larvae was investigated in a rational search for insecticides. The results showed that these isoquinolines presented moderate larvicidal activity, that the presence of a substituent is needed on carbon 1 for such activity to be presented and that it may be possible to develop novel insecticidal compounds having potential use in controlling insects by appropriate structural modification of 1-phenylisoquinolines. This article presents a possible structure-larvicidal activity relationship for isoquinolinic compounds. PMID- 22044224 TI - Lipophilic and amphiphilic interactions in glycoprotein 41: targets for therapy. PMID- 22044221 TI - Epigenetic landscape of pluripotent stem cells. AB - SIGNIFICANCE: Derived from the inner cell mass of the preimplantation embryo, embryonic stem cells are prototype pluripotent stem (PS) cells that have the ability of self-renewal and differentiation into almost all cell types. Exploration of the mechanisms governing this pluripotency is important for understanding reprogramming mechanisms and stem cell behavior of PS cells and can lead to enhancing reprogramming efficiency and other applications. RECENT ADVANCES: Induced pluripotent stem cells are recently discovered PS cells that can be derived from somatic cells by overexpression of pluripotency-related transcription factors. Recent studies have shown that transcription factors and their epigenetic regulation play important roles in the generating, maintaining, and differentiating these PS cells. Recent advances in sequencing technologies allow detailed analysis of target epigenomes and microRNAs (miRs), and have revealed unique epigenetic marks and miRs for PS cells. CRITICAL ISSUES: Epigenetic modifications of genes include histone modifications, DNA methylation, and chromatin remodeling. Working closely with epigenetic modifiers, miRs play an important role in inducing and maintaining pluripotency. FUTURE DIRECTIONS: The dynamic changes in epigenetic marks during reprogramming and their role in cell fate changes are being uncovered. This review focuses on these new advances in the epigenetics of PS cells. PMID- 22044226 TI - Amphipathic properties of HIV-1 gp41 fusion inhibitors. AB - Small molecule inhibition of HIV fusion has been an elusive goal, despite years of effort by both pharmaceutical and academic laboratories. In this review, we will discuss the amphipathic properties of both peptide and small molecule inhibitors of gp41-mediated fusion. Many of the peptides and small molecules that have been developed target a large hydrophobic pocket situated within the grooves of the coiled coil, a potential hotspot for inhibiting the trimer of hairpin formation that accompanies fusion. Peptide studies reveal molecular properties required for effective inhibition, including elongated structure and lipophilic or amphiphilic nature. The characteristics of peptides that bind in this pocket provide features that should be considered in small molecule development. Additionally, a novel site for small molecule inhibition of fusion has recently been suggested, involving residues of the loop and fusion peptide. We will review the small molecule structures that have been developed, evidence pointing to their mechanism of action and strategies towards improving their affinity. The data points to the need for a strongly amphiphilic character of the inhibitors, possibly as a means to mediate the membrane - protein interaction that occurs in gp41 in addition to the protein - protein interaction that accompanies the fusion activating conformational transition. PMID- 22044225 TI - Targeting HIV-1 gp41-induced fusion and pathogenesis for anti-viral therapy. AB - HIV gp41 is a metastable protein whose native conformation is maintained in the form of a heterodimer with gp120. The non-covalently associated gp41/gp120 complex forms a trimer on the virus surface. As gp120 engages with HIV's receptor, CD4, and coreceptor, CXCR4 or CCR5, gp41 undergoes several conformational changes resulting in fusion between the viral and cellular membranes. Several lipophilic and amphiphilic domains have been shown to be critical in that process. While the obvious function of gp41 in viral entry is well-established its role in cellular membrane fusion and the link with pathogenesis are only now beginning to appear. Recent targeting of gp41 via fusion inhibitors has revealed an important role of this protein not only in viral entry but also in bystander apoptosis and HIV pathogenesis. Studies by our group and others have shown that the phenomenon of gp41-mediated hemifusion initiates apoptosis in bystander cells and correlates with virus pathogenesis. More interestingly, recent clinical evidence suggests that gp41 mutants arising after Enfuvirtide therapy are associated with CD4 cell increase and immunological benefits. This has in turn been correlated to a decrease in bystander apoptosis in our in vitro as well as in vivo assays. Although a great deal of work has been done to unravel HIV-1 gp41-mediated fusion mechanisms, the factors that regulate gp41-mediated fusion versus hemifusion and the mechanism by which hemifusion initiates bystander apoptosis are not fully understood. Further insight into these issues will open new avenues for drug development making gp41 a critical anti-HIV target both for neutralization and virus attenuation. PMID- 22044227 TI - Membrane-transferring regions of gp41 as targets for HIV-1 fusion inhibition and viral neutralization. AB - The fusogenic function of HIV-1 gp41 transmembrane Env subunit relies on two different kinds of structural elements: i) a collapsible ectodomain structure (the hairpin or six-helix bundle) that opens and closes, and ii) two membrane- transferring regions (MTRs), the fusion peptide (FP) and the membrane-proximal external region (MPER), which ensure coupling of hairpin closure to apposition and fusion of cell and viral membranes. The isolation of naturally produced short peptides and neutralizing IgG-s, that interact with FP and MPER, respectively, and block viral infection, suggests that these conserved regions might represent useful targets for clinical intervention. Furthermore, MTR-derived peptides have been shown to be membrane-active. Here, it is discussed the potential use of these molecules and how the analysis of their membrane activity in vitro could contribute to the development of HIV fusion inhibitors and effective immunogens. PMID- 22044228 TI - Targeting HIV-1 gp41 in close proximity to the membrane using antibody and other molecules. AB - HIV-1 envelope glycoprotein (Env) spikes are supported at the viral membrane interface by a highly conserved and hydrophobic region of gp41, designated the membrane-proximal external region (MPER). The MPER is mandatory for infection of host cells by HIV-1, and is the target of some of the most broadly neutralizing antibodies described to date. As such, the MPER is also of considerable interest for HIV vaccine design. However, structural models indicate that the MPER assumes distinct conformations prior to and leading up to Env-mediated fusion. Thus, the more of these distinct conformations that antibodies and inhibitors can recognize will likely be the better for antiviral potency. In addition to its flexibility, the MPER is lipophilic and its accessibility to bulky macromolecules is limited by steric and kinetic blocks that present particular challenges for eliciting HIV 1 neutralizing antibodies. Moreover, the ability of the MPER and viral membrane to combine as a complex has critical mechanistic implications for molecules that target lipid-bound and/or unbound states. Interestingly, membrane affinity frequently appears to enhance the potency of both fusion inhibitors and antibodies to different sites on gp41. We therefore highlight mechanisms to be harnessed in targeting membraneproximal sites on HIV gp41 for both vaccine and fusion inhibitor design. Such design efforts will likely need to draw upon knowledge of MPER structure and function, and may in turn inform analogous approaches to MPERs of other enveloped viruses and systems. PMID- 22044230 TI - Culture and the quest for universal principles in moral reasoning. AB - The importance of including cultural perspectives in the study of human cognition has become apparent in recent decades, and the domain of moral reasoning is no exception. The present review focuses on moral cognition, beginning with Kohlberg's model of moral development which relies heavily on people's justifications for their judgments and then shifting to more recent theories that rely on rapid, intuitive judgments and see justifications as more or less irrelevant to moral cognition. Despite this dramatic shift, analyses of culture and moral decision-making have largely been framed as a quest for and test of universal principles of moral judgment. In this review, we discuss challenges that remain in trying to understand crosscultural variability in moral values and the processes that underlie moral cognition. We suggest that the universalist framework may lead to an underestimation of the role of culture in moral reasoning. Although the field has made great strides in incorporating more and more cultural perspectives in order to understand moral cognition, theories of moral reasoning still do not allow for substantial variation in how people might conceptualize the domain of the moral. The processes that underlie moral cognition may not be a human universal in any simple sense, because moral systems may play different roles in different cultures. We end our review with a discussion of work that remains to be done to understand cultural variation in the moral domain. PMID- 22044229 TI - Biochemistry and biophysics of HIV-1 gp41 - membrane interactions and implications for HIV-1 envelope protein mediated viral-cell fusion and fusion inhibitor design. AB - Human immunodeficiency virus type 1 (HIV-1), the pathogen of acquired immunodeficiency syndrome (AIDS), causes ~2 millions death every year and still defies an effective vaccine. HIV-1 infects host cells through envelope protein - mediated virus-cell fusion. The transmembrane subunit of envelope protein, gp41, is the molecular machinery which facilitates fusion. Its ectodomain contains several distinguishing functional domains, fusion peptide (FP), Nterminal heptad repeat (NHR), C-terminal heptad repeat (CHR) and membrane proximal extracellular region (MPER). During the fusion process, FP inserts into the host cell membrane, and an extended gp41 prehairpin conformation bridges the viral and cell membranes through MPER and FP respectively. Subsequent conformational change of the unstable prehairpin results in a coiled-coil 6-helix bundle (6HB) structure formed between NHR and CHR. The energetics of 6HB formation drives membrane apposition and fusion. Drugs targeting gp41 functional domains to prevent 6HB formation inhibit HIV-1 infection. T20 (enfuvirtide, Fuzeon) was approved by the US FDA in 2003 as the first fusion inhibitor. It is a 36-residue peptide from the gp41 CHR, and it inhibits 6HB formation by targeting NHR and lipids. Development of new fusion inhibitors, especially small molecule drugs, is encouraged to overcome the shortcomings of T20 as a peptide drug. Hydrophobic characteristics and membrane association are critical for gp41 function and mechanism of action. Research in gp41-membrane interactions, using peptides corresponding to specific functional domains, or constructs including several interactive domains, are reviewed here to get a better understanding of gp41 mediated virus-cell fusion that can inform or guide the design of new HIV-1 fusion inhibitors. PMID- 22044231 TI - Parent-adolescent relationships and social adjustment: the case of a collectivistic culture. AB - This study examined how parent-adolescent relationships are related to adolescent loneliness, interpersonal difficulties and school adjustment among Israeli Arabs. Two hundred and thirty-one 11th graders (103 boys and 128 girls) and their homeroom teachers participated. Four groups of adolescents were identified according to parenting practice profiles: Adolescents in the harsh parenting group reported the highest levels of loneliness, those in the distant and mixed groups reported midway levels of loneliness, and those in the warm group showed the lowest degree of loneliness and the lowest levels of interpersonal problems. Overall, boys reported higher levels of peer-related loneliness and lower levels of affinity for aloneness than girls. Gender interacted significantly with parenting group, with girls in the harsh parenting group exhibiting greater parent-related loneliness and affinity for loneliness, while boys exhibited more peer-related loneliness. The important role that parents play in their children's social adjustment is discussed in relation to gender and culture. PMID- 22044232 TI - Collective school-type identity: predicting students' motivation beyond academic self-concept. AB - In Germany, according to their prior achievement students are tracked into different types of secondary school that provide profoundly different options for their future educational careers. In this paper we suggest that as a result, school tracks clearly differ in their social status or reputation. This should translate into different collective school-type identities for their students, irrespective of the students' personal academic self-concepts. We examine the extent to which collective school-type identity systematically varies as a function of the school track students are enrolled in, and the extent to which students' collective school-type identity makes a unique contribution beyond academic self-concept and school track in predicting scholastic motivation. In two cross-sectional studies a measure of collective school-type identity is established and applied to explain motivational differences between two school tracks in Berlin. In Study 1 (N = 39 students) the content of the collective school-type identity is explored by means of an open format questionnaire. Based on these findings a structured instrument (semantic differential) to measure collective school-type identity is developed. In Study 2 (N = 1278 students) the assumed structure with four subscales (Stereotype Achievement, Stereotype Motivation, Stereotype Social, and Compensation) is proved with confirmatory factor analysis. This measure is used to compare the collective school-type identity across school tracks and predict motivational outcomes. Results show large differences in collective school-type identity between students of different school tracks. Furthermore, these differences can explain motivational differences between school tracks. Collective school-type identity has incremental predictive power for scholastic motivation, over and above the effects of academic self-concept and school track. PMID- 22044233 TI - The relationship between the need for closure and deviant bias: an investigation of generality and process. AB - The need for closure predicts an evaluative bias against people whose opinions or behaviors deviate from those of other members of their social groups. In the present study, we investigated whether the relationship between the need for closure and deviant bias generalized to nonsocial stimuli, and we examined the process underlying this relationship. Sixty-one undergraduate students completed measures of the need for closure, the need for structure, intolerance for ambiguity, and the ability to be decisive and achieve cognitive structure. They then rated their liking for letters of the Latin alphabet ("A" & "B") whose locations were consistent and inconsistent with relevant categories ("A circle" and "B circle"). Participants liked category-inconsistent letters less than category-consistent letters. Measures related to the need for structure and closed-mindedness correlated positively with this deviant bias, whereas measures related to the ability to be decisive and achieve cognitive structure did not. These results imply that the relationship between the need for closure and deviant bias is a relatively basic and pervasive effect that is not unique to social deviance and is driven by the need for structure and closed-mindedness. Implications for social and nonsocial stimuli are discussed. PMID- 22044234 TI - The effect of music-induced mood on attentional networks. AB - Attention network theory suggests that there are three separate neural networks that execute the discrete functions of alerting, orienting, and executive attention. Previous research on the influence of mood on attention has shown subtle and inconsistent results. The attention network theory may aid in clarifying the influence of mood on attention. The present study investigated the influence of mood on attentional networks in a normal population. Participants performed the Attention Network Test (ANT), which provides functional measures of alerting, orienting, and executive attention. Positive or negative mood was induced by listening to music with a positive or negative valence, respectively; neutral mood was induced by reading a collection of basic facts about China. The results revealed that negative mood led to a significantly higher alerting efficiency relative to other moods, while there were no significant mood effects on orienting or executive attention efficiency. According to the algorithm underlying the ANT, the higher alerting efficiency in the negative mood condition can be attributed to relatively greater benefits of cueing effects. The findings are discussed in the context of the noradrenergic system and of evolutionary significance. Specifically, the increase in the alerting function during negative mood states may be due to the modulation effect of negative mood on the noradrenergic system, and/or to the survival benefit resulting from an increase in automatic vigilance towards negative information. The current results suggest that as the influence of negative mood on attention appears to specifically consist in an enhanced alerting function, it may not be found in studies where the three attentional networks are not dissociated. PMID- 22044235 TI - Exploring the factors contributing to empowerment of Turkish migrant women in the UK. AB - This study examined the role of demographic factors (length of stay, education and language level), perceived discrimination, social support, four acculturation attitudes, and psychological distress in predicting empowerment among Turkish migrant women in the UK. The study sample comprised 248 Turkish migrant women (mean age: 34.38; SD: 7.6) living in London. Self-report questionnaires were used to assess empowerment, social support, acculturation attitude and psychological distress. The study hypothesized that perceived discrimination; acculturation attitudes of separation, assimilation and marginalization; and psychological distress would be negative predictors of empowerment and that social support and an integration acculturation attitude would be positive predictors of empowerment. To some extent, the study findings supported this hypothesis. Hierarchical regression analysis indicated psychological distress to be the most significant predictor of empowerment, with other significant predictors including level of education and social support. More specifically, lower levels of psychological distress and higher levels of education and social support appeared to predict greater empowerment. Based on these findings, it can be concluded that level of education and social support may function as protective factors and that psychological distress may function as a risk factor for empowerment in the migration context. The paper discusses the findings of this study in relation to the previous literature and notes their implications for future research and practice. PMID- 22044236 TI - The relationship between personality, social functioning, and depression: a structural equation modeling analysis. AB - The relationship between personality, social functioning, and depression remains unclear. The present study employs structural equation modeling to examine the mediating role of social functioning between harm avoidance (HA), self directedness (SD), and depression. A sample of 902 individuals completed a self report questionnaire consisting of the following scales: HA and SD subscales of the Temperament and Character Inventory (TCI), Beck Depression Inventory (BDI), and Social Adaptation Self-Evaluation Scale (SASS). Structural equation modeling via analysis of moment structure was used to estimate the fit of nine related models. Results indicated that social functioning is a mediator between harm avoidance or self-directness and depression. Self-directedness was also shown to have direct effects on depression. The results support the social reinforcement theory of depression and provide a theoretical account of how the variables are related based on correlation methods. Suggestions are offered for future experimental and longitudinal research. PMID- 22044238 TI - Polycationic chitosan-conjugated photosensitizer for antibacterial photodynamic therapy. AB - The complex nature of bacterial cell membrane and structure of biofilm has challenged the efficacy of antimicrobial photodynamic therapy. This study was aimed to synthesize a polycationic chitosan-conjugated rose bengal (CSRB) photosensitizer and test its antibiofilm efficacy on Enterococcus faecalis (gram positive) and Pseudomonas aeruginosa (gram negative) using photodynamic therapy. During experiments, CSRB was tested along with an anionic photosensitizer rose bengal (RB) and a cationic photosensitizer methylene blue (MB) for uptake and killing efficacy on 7-day-old E. faecalis and P. aeruginosa biofilms. Microbiological culture based analysis was used to analyze the cell viability, while laser scanning confocal microscopy (LSCM) was used to examine the structure of biofilm. The synthesized CSRB showed absorbance spectrum similar to the RB. The concentration of CSRB uptaken by both the bacterial biofilms was significantly higher than that of RB and MB (P < 0.05). Photoactivation resulted in significantly higher elimination of both bacterial biofilms sensitized with CSRB than RB and MB. The structure of biofilm under LSCM was found to be disrupted following CSRB treatment. The present study highlighted the importance of inherent cell membrane permeabilizing effect of chitosan and increased cell/biofilm uptake of conjugated photosensitizer to produce significant antibiofilm efficacy during photodynamic therapy. PMID- 22044239 TI - Clarifying the relationship between AS dimensions and PTSD symptom clusters: are negative and positive affectivity theoretically relevant constructs? AB - The association between anxiety sensitivity (AS) and posttraumatic stress disorder (PTSD) has been established in contemporary literature; however, research is divided over the nature of specific relationships between AS dimensions and PTSD symptoms clusters. Further, a paucity of research has examined the AS and PTSD relationship while accounting for theoretically relevant variables, such as negative (NA) and positive affect (PA). The purpose of the current study was twofold: first, to clarify divergent findings regarding the contribution of AS dimensions to PTSD symptom clusters, and, second, to further assess the relevance of NA and PA within the AS/PTSD relationship. Hierarchal regression analyses showed that, beyond shared variance attributable to NA and PA, AS somatic concerns were significantly associated with three of four PTSD symptom (i.e., reexperiencing, numbing, hyperarousal), AS cognitive concerns were only associated with hyperarousal, and AS socially observable symptoms were not significantly associated with any PTSD symptom clusters. These findings suggest that AS somatic concerns are the most robust predictor of variance within the AS/PTSD relationship and further clarify the theoretical importance of NA and PA within this relationship. Comprehensive results, implication, and directions for future research are discussed. PMID- 22044240 TI - Topical tacrolimus ointment for the treatment of lichen sclerosus, comparing genital and extragenital involvement. AB - Lichen sclerosus is a chronic inflammatory dermatosis presenting with significant sclerosis, atrophy and pruritus. The treatment for this condition remains unsatisfactory, with potent corticosteroids being the most effective therapy. In this study, we investigated the efficacy and safety of tacrolimus ointment in patients with genital and extragenital lichen sclerosus. Sixteen patients with active lichen sclerosus (10 with anogenital and six with extragenital localization) were treated with topical tacrolimus ointment twice daily. The therapeutic effects were evaluated according to 3 grades: complete response (>75% improvement), partial response (25-75% improvement), or no response (<25% improvement). Applications were continued until complete disappearance or stabilization of the cutaneous lesions. In addition, we conducted telephone surveys to determine the long-term treatment outcome and relapse rate. Objective response to therapy occurred in nine of 10 patients (90%) with anogenital and one of six patients (16.7%) with extragenital lesions. Out of 10 patients with anogenital lichen sclerosus, five showed more than 75% improvement. Complete, partial and no response were achieved in five (50%), four (40%) and one (10%) patient, respectively. During the follow-up period of a mean of 29.3 months, six of nine patients had a relapse of symptoms. However, most patients with extragenital involvement did not respond to tacrolimus, except one patient showing partial response. No significant adverse effects were observed. Topical tacrolimus ointment was a safe and effective treatment for genital lichen sclerosus and should be used for long-term duration to prevent relapse. However, it was not useful for patients with extragenital lichen sclerosus. PMID- 22044242 TI - Fabrication of biomaterials via controlled protein bubble generation and manipulation. AB - In this work, we utilize a recently developed microbubbling process to generate controlled protein (bovine serum albumin, BSA) coated bubbles and then manipulate these to fabricate a variety of structures suitable for several generic biomedical applications, tissue engineering, and biosensor coatings. Using BSA solutions with varying concentrations (20, 25, and 30 wt %) and cross-linking (terephthaloyl chloride) mechanisms, structures were fabricated including porous thin films with variable pore sizes and thickness (partially cross-linked coupled to bubble breakdown), scaffolds with variable pore morphologies (fully cross linked), and coated bubbles (no cross-linking), which can be used as stand-alone delivery devices and contrast agents. The movement of typical biosensor chemicals (catechol and hydrogen peroxide) across appropriate film structures was studied. The potential of formed scaffold structures for tissue engineering applications was demonstrated using mouse cell lines (L929). In addition to low cost, providing uniform structure generation and high output, the size of the bubbles can easily be controlled by adjusting simplistic processing parameters. The combination of robust processing and chemical modification to uniform macromolecule bubbles can be utilized as a competing, yet novel, tool with current technologies and processes in advancing the biomaterials and biomedical engineering remits. PMID- 22044241 TI - Stressful life events, perceived stress, and 12-month course of geriatric depression: direct effects and moderation by the 5-HTTLPR and COMT Val158Met polymorphisms. AB - Although the relation between stressful life events (SLEs) and risk of major depressive disorder is well established, important questions remain about the effects of stress on the course of geriatric depression. Our objectives were (1) to examine how baseline stress and change in stress is associated with course of geriatric depression and (2) to test whether polymorphisms of serotonin transporter (5-HTTLPR) and catechol-O-methyltransferase (COMT Val158Met) genes moderate this relation. Two-hundred and sixteen depressed subjects aged 60 years or older were categorized by remission status (Montgomery-Asberg depression rating scale<=6) at 6 and 12 months. At 6 months, greater baseline numbers of self-reported negative and total SLEs and greater baseline perceived stress severity were associated with lower odds of remission. At 12 months, only baseline perceived stress predicted remission. When we examined change in stress, 12-month decrease in negative SLEs and level of perceived stress were associated with improved odds of 12-month remission. When genotype data were included, COMT Val158Met genotype did not influence these relations. However, when compared with 5-HTTLPR L/L homozygotes, S allele carriers with greater baseline numbers of negative SLEs and with greater decrease in negative SLEs were more likely to remit at 12 months. This study demonstrates that baseline SLEs and perceived stress severity may influence the 12-month course of geriatric depression. Moreover, changes in these stress measures over time correlate with depression outcomes. 5-HTTLPR S carriers appear to be more susceptible to both the effects of enduring stress and the benefit of interval stress reduction. PMID- 22044243 TI - CD40 and tumour necrosis factor-alpha co-operate to up-regulate inducuble nitric oxide synthase expression in macrophages. AB - Regulation of inducible nitric oxide synthase (NOS2) expression is important given the role of this enzyme in inflammation, control of infections and immune regulation. In contrast to tumour necrosis factor-alpha (TNF-alpha) alone or CD40 stimulation alone, simultaneous stimulation of mouse macrophages through CD40 ligation and TNF-alpha led to up-regulation of NOS2 and nitric oxide production. This response was of functional relevance because CD40/TNF-alpha-stimulated macrophages acquired nitric oxide-dependent anti-Leishmania major activity. CD40 plus TNF-alpha up-regulated NOS2 independently of interferon-gamma, interferon alpha/beta and interleukin-1. TNF receptor-associated factor 6 (TRAF6), an adapter protein downstream of CD40, appears to be required for NOS2 up-regulation because a CD40-TRAF6 blocking peptide inhibited up-regulation of NOS2 in CD40/TNF alpha-stimulated macrophages. CCAAT/enhancer-binding protein-beta (C/EBPbeta), a transcription factor activated by TNF-alpha but not CD40, was required for NOS2 up-regulation because this enzyme was not up-regulated when C/EBPbeta(-/-) macrophages received CD40 plus TNF-alpha stimulation. These results indicate that CD40 and TNF-alpha co-operate to up-regulate NOS2, probably via the effect of TRAF6 and C/EBPbeta. PMID- 22044244 TI - Quantification of Campylobacter and Salmonella in cattle before, during, and after the slaughter process. AB - Salmonella and Campylobacter cause a significant number of human illnesses globally, most of which are food related. Cattle can be asymptomatic carriers of both of these pathogens. The objective of this study was to determine the association between the concentration of Salmonella and Campylobacter pre- and postharvest in cattle. Samples were collected from each of 98 individually identified cattle during the periharvest and postharvest period. For each animal, four different phases were sampled: on farm (fecal sample), poststunning and exsanguination (hide sponge and rectal content sample [lairage]), prechilling (carcass sponge), and final product (ground meat). Salmonella and Campylobacter were cultured and quantified at each stage by using the direct dilution and most probable number (MPN) method. Salmonella was not isolated from any sample. The proportion (%) of samples that were Campylobacter positive was 77, 82, 97, 55, and 12 for farm, rectal content, hide, carcass, and meat samples respectively. The mean Campylobacter concentration for each sample was as follows: fecal sample from farm, 3.7*10(4) cfu/g; rectal content sample from lairage, 1.6*10(5) cfu/g; hide sponge, 0.9 cfu/cm(2); carcass sponge, 8.7 cfu/half carcass; and meat, 1.1 cfu/g. There were no associations between Campylobacter concentrations for any two sample types. This lack of association could indicate that there is an environmental reservoir that can contaminate the final meat product, or since the majority of animals were positive entering the slaughter process, that the process itself reduces the load of Campylobacter regardless of the initial concentration. In addition, contamination of beef may be more strongly associated with periharvest practices than animal carriage rates. PMID- 22044245 TI - Cucurbitane glucosides from the root of Machilus yaoshansis. AB - Seven new cucurbitane triterpene glucosides (1-5, 8, and 9) and five known analogues (6, 7, 10, cucurbitacin I 2-O-beta-d-glucopyranoside, and khekadaengoside K) have been isolated from an ethanol extract of roots of Machilus yaoshansis. Compounds 1 and 2 have an unusual 16,23:22,25-diepoxy unit, 4 is an uncommon cucurbitane 25-carbamate with the carbamoyl amino group attached at C-24 to form an oxazolidinone ring in the side chain, and 8 is the first example of a trinorcucurbitane derivative. The configurations in several pairs of C-24 epimeric cucurbitacins with 24,25-dihydroxy-22-one side chains were assigned, and the validity of J(23a,24) and J(23b,24) values to differentiate the configuration at C-24 in these cucurbitane derivatives is discussed. Compounds 2 4 showed in vitro activity against protein tyrosine phosphatase 1B with IC50 values of 8.63, 2.81, and 4.26 MUM, respectively. Cucurbitacin E 2-O-beta-d glucopyranoside (10) showed selective cytotoxicity against BGC-823 and A549 cancer cells with IC50 values of 4.98 and 3.20 MUM, respectively. PMID- 22044246 TI - Nonlinear deformation of a ferrofluid droplet in a uniform magnetic field. AB - This paper reports experimental and numerical results of the deformation of a ferrofluid droplet on a superhydrophobic surface under the effect of a uniform magnetic field. A water-based ferrofluid droplet surrounded by immiscible mineral oil was stretched by a magnetic field parallel to the substrate surface. The results show that an increasing flux density increases the droplet width and decreases the droplet height. A numerical model was established to study the equilibrium shape of the ferrofluid droplet. The governing equations for physical fields, including the magnetic field, are solved by the finite volume method. The interface between the two immiscible liquids was tracked by the level-set method. Nonlinear magnetization was implemented in the model. Comparison between experimental and numerical results shows that the numerical model can predict well the nonlinear deformation of a ferrofluid droplet in a uniform magnetic field. PMID- 22044250 TI - Physicochemical characterization of solute retention in solvent resistant nanofiltration: the effect of solute size, polarity, dipole moment, and solubility parameter. AB - Growing interest in nanofiltration for solvent purification requires a fundamental understanding of the physicochemical mechanisms of solute retention in organic solvent nanofiltration. In this study, the retention of a similar series of azo dyes with approximately similar molar mass (around 350 Da) by four nanofiltration membranes was studied. The membranes used are commercially available polymeric nanofiltration membranes with molecular weight cutoff between 150 and 300 Da (DuraMem150, StarMem122, NF270 and Desal-Dk). In order to correlate the retention with the size of the molecules, which is assumed to be one of the main factors that determines the retention, use was made of different parameters for the molecular size: molar mass, the Stokes diameter, the equivalent molar diameter, and the cavity surface in methanol and ethanol. All parameters were calculated by using molecular dynamics simulations. For each size parameter, the correlation with retention in nanofiltration experiments was calculated. For the StarMem122 membrane, zero retentions were observed due to the swelling of the membrane and pore size enlargement in methanol and ethanol. For the three other membranes, a fairly good correlation of the retention with the size could only be observed if the size difference between compounds is sufficiently large. Two other factors were studied by using molecular dynamics, i.e., the polarity of the molecule and the electron density of the molecule. The importance of these factors depends on the structure of the molecule as well as the functional groups of the polymer. A very good correlation has been observed for retention of dyes versus their dipole moment. Finally, the effect of solubility parameters of dyes on their retention did not show any significant effect. PMID- 22044248 TI - Tau-targeted treatment strategies in Alzheimer's disease. AB - With populations ageing worldwide, the need for treating and preventing diseases associated with high age is pertinent. Alzheimer's disease (AD) is reaching epidemic proportions, yet the currently available therapies are limited to a symptomatic relief, without halting the degenerative process that characterizes the AD brain. As in AD cholinergic neurons are lost at high numbers, the initial strategies were limited to the development of acetylcholinesterase inhibitors, and more recently the NMDA receptor antagonist memantine, in counteracting excitotoxicity. With the identification of the protein tau in intracellular neurofibrillary tangles and of the peptide amyloid-beta (Abeta) in extracellular amyloid plaques in the AD brain, and a better understanding of their role in disease, newer strategies are emerging, which aim at either preventing their formation and deposition or at accelerating their clearance. Interestingly, what is well established to combat viral diseases in peripheral organs - vaccination - seems to work for the brain as well. Accordingly, immunization strategies targeting Abeta show efficacy in mice and to some degree also in humans. Even more surprising is the finding in mice that immunization strategies targeting tau, a protein that forms aggregates in nerve cells, ameliorates the tau associated pathology. We are reviewing the literature and discuss what can be expected regarding the translation into clinical practice and how the findings can be extended to other neurodegenerative diseases with protein aggregation in brain. PMID- 22044251 TI - Surfactant and perfluorocarbon aerosolization during different mechanical ventilation strategies by means of inhalation catheters: an in vitro study. AB - BACKGROUND: Aerosol delivery of surfactant and perfluorocarbon (PFC) is a desirable therapeutic approach for the treatment of various lung diseases in patients undergoing mechanical ventilation. However, the behavior of these substances during aerosolization differs significantly from that of aqueous solutions. In particular, the high vapor pressure of many PFCs tends to result in greater evaporation during mechanical ventilation. METHODS: Three PFCs and surfactant were aerosolized during mechanical ventilation by means of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, and IC-1.4), with their aerosol generating tip placed at the distal end of the endotracheal tube (i.d. 4 mm). The influence of four different ventilation strategies on aerosol production rate and PFC and surfactant recovery was studied. The changes in intrapulmonary pressure produced by the air jets of each IC were measured. RESULTS: With IC-1.23 and IC-1.1, the highest rates of aerosol production were achieved using FC75 (2.27+/-0.18 and 0.76+/-0.01, respectively) followed by PFOB (1.74+/-0.06 and 0.56+/-0.04), PFD (0.82+/-0.01 and 0.21+/ 0.01), and surfactant (0.42+/-0.05 and 0.092+/-0.01). With IC-1.4 modest aerosol production was obtained irrespective of the aerosolized compound. Mechanical ventilation influenced aerosol recovery, with the trend being toward recovering higher percentages of the compounds with lower peak inspiratory pressure (PIP) and lower respiratory rate (RR) settings. The highest percentages of the initial volume were recovered with IC-1.23 (between 65.43%+/-4.2 FC75 and 90.21%+/-4.71 surfactant) followed by IC-1.1 (between 46.48%+/-4.46 FC75 and 73.19%+/-2.82 PFOB) and IC-1.4 (between 4.65%+/-4.36 FC75 and 63.24%+/-9.71 surfactant). Each of three of the ICs were found to increase the intrapulmonary pressure by about 2 3 cmH2O during mechanical ventilation. CONCLUSIONS: Despite of mechanical ventilation, IC-1.23 and IC-1.1 were able to deliver significant amounts of surfactant and perfluorocarbon to the lung model. Changes in PIP and RR directly influence the percentage of surfactant and perfluorocarbon recovered. PMID- 22044252 TI - Comparison of single-incision laparoscopic distal gastrectomy and laparoscopic distal gastrectomy for gastric cancer in a porcine model. AB - INTRODUCTION: The single-incision laparoscopic approach may be suitable for several intra-abdominal surgical interventions, but its usefulness for treating gastric cancer has not been established. The aim of this study is to compare the perioperative outcomes of single-incision laparoscopic distal gastrectomy (SIDG) and conventional laparoscopic distal gastrectomy (LDG) by using a porcine model. METHODS: Ten pigs were used to compare the perioperative outcomes of SIDG and LDG. All were subjected to the same distal gastrectomy with D1+beta lymph node dissection method. Specimens retrieved during the operation were subjected to manual lymph node picking and counting. To evaluate the inflammatory reactions, white blood cell (WBC) counts and C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-alpha levels were measured before and 1 hour, 1 day, and 5 days after surgery. The pigs were sacrificed 1 week after surgery. RESULTS: The procedures were successfully performed in all pigs. The SIDG group lost more weight than the LDG group, but this was not statistically significant (3.34+/-2.36 kg versus 1.94+/-1.61 kg, P=.305). The SIDG group was associated with a significantly longer operation time (140+/-14.14 minutes versus 93+/-4.47 minutes, P<.001), but it had a similar mean number of resected lymph nodes (25+/ 2.45 versus 22+/-4.87, P=.393). Variance analysis failed to detect significant WBC, CRP, IL-6, or TNF-alpha differences. At sacrifice, one pig from each group exhibited anastomosis narrowing. CONCLUSIONS: This animal study shows that SIDG can be applicable for treating gastric cancer with similar inflammatory reaction and complication rates when compared with LDG. Comparative human study is necessary to demonstrate the benefits of SIDG compared with standard laparoscopic surgery. PMID- 22044253 TI - Emissions impacts of wind and energy storage in a market environment. AB - This study examines the emissions impacts of adding wind and energy storage to a market-based electric power system. Using Texas as a case study, we demonstrate that market power can greatly effect the emissions benefits of wind, due to most of the coal-fired generation being owned by the two dominant firms. Wind tends to have less emissions benefits when generators exercise market power, since coal fired generation is withheld from the market and wind displaces natural gas-fired generators. We also show that storage can have greater negative emissions impacts in the presence of wind than if only storage is added to the system. This is due to wind increasing on- and off-peak electricity price differences, which increases the amount that storage and coal-fired generation are used. We demonstrate that this effect is exacerbated by market power. PMID- 22044256 TI - Structural, elastic constant, and vibrational properties of wurtzite gallium nitride: a first-principles approach. AB - Perdew-Wang proposed generalized gradient approximation (GGA) is used in conjunction with ultrasoft pseudopotential to investigate the structural, elastic constant, and vibrational properties of wurtzite GaN. The equilibrium lattice parameters, axial ratio, internal parameter, bulk modulus, and its pressure derivative are calculated. The effect of pressure on equilibrium lattice parameters, axial ratio, internal parameter (u), relative volume, and bond lengths parallel and perpendicular to the c-axis are discussed. At 52 GPa, the relative volume change is observed to be 17.8%, with an abrupt change in bond length. The calculated elastic constants are used to calculate the shear wave speeds in the [100] and [001] planes. The finite displacement method is employed to calculate phonon frequencies and the phonon density of states. The first- and second-order pressure derivative and volume dependent Gruneisen parameter (gamma(j)) of zone-center phonon frequencies are discussed. These phonon calculations calculated at theoretical lattice constants agree well with existing literature. PMID- 22044255 TI - Antitumor activity of peptide amphiphile nanofiber-encapsulated camptothecin. AB - Self-assembling peptide amphiphile (PA) nanofibers were used to encapsulate camptothecin (CPT), a naturally occurring hydrophobic chemotherapy agent, using a solvent evaporation technique. Encapsulation by PA nanofibers was found to improve the aqueous solubility of the CPT molecule by more than 50-fold. PAs self assembled into nanofibers in the presence of CPT as demonstrated by transmission electron microscopy. Small-angle X-ray scattering results suggest a slight increase in diameter of the nanofiber to accommodate the hydrophobic cargo. In vitro studies using human breast cancer cells show an enhancement in antitumor activity of the CPT when encapsulated by the PA nanofibers. In addition, using a mouse orthotopic model of human breast cancer, treatment with PA nanofiber encapsulated CPT inhibited tumor growth. These results highlight the potential of this model PA system to be adapted for delivery of hydrophobic therapies to treat a variety of diseases including cancer. PMID- 22044254 TI - Epithelial barrier biology: good fences make good neighbours. AB - The external surfaces of the body, such as the skin and the gastrointestinal mucosal membrane, are an important line of defence preventing the invasion of microorganisms and their products. Mucosal immune cells, especially intraepithelial lymphocytes, are involved in maintaining the integrity of these epithelial barriers. They contribute towards the tolerance to commensal organisms, which occupy these same sites, and to the immune responses against harmful organisms and their products. The composition of the microbiota is influenced by immune cells as well as external environmental factors, especially the use of antibiotics and diet. There is an increasing appreciation that the microbiota affects systemic immune responses in addition to local immunity. Failure to control the occupancy by microorganisms may result in the disruption of the delicate homeostasis between beneficial and harmful microorganisms and contribute to inflammatory pathologies. This review will discuss some of our current understanding of the impact of immune cells and diet on the microbiota. PMID- 22044257 TI - Circadian cycle and chronotherapeutics: recent trend for the treatment of various biological disorders. AB - Chronotherapeutics is a novel approach in the treatment of various biological disorders. Circadian rhythms are the important factor in the biological cycle through which the drug dosing should be matched with the rhythms of the diseases for the successful treatment of the illness or the disorder. Through this review it shows that different chronotherapeutic approaches have been successfully employed for treating different biological disorders through different formulation methods, and discussion of recent patents. PMID- 22044258 TI - The impact of choice on retributive reactions: how observers' autonomy concerns shape responses to criminal offenders. AB - The present research examined the psychological origins of retributive reactions, which are defined as independent observers' anger-based emotions, demonized perceptions, and punishment intentions in response to criminal offenders. Based on the idea that society's justice system has an autonomy-protective function, we reason that chronic autonomy interacts with situational autonomy cues (i.e., opportunities to make choices) to predict retributive reactions to criminal offenders. More specifically, we hypothesized that choice opportunities in an unrelated decision-making context would prompt people to display stronger retributive reactions to offenders than no-choice opportunities, and that these effects of choice would be particularly pronounced among people who chronically experience deprivation of autonomy needs. Results from two experiments supported this hypothesis. It is concluded that retributive reactions to criminal offenders originate from a desire to regulate basic autonomy needs. PMID- 22044259 TI - Modification of an acetone-sodium dodecyl sulfate disruption method for cellular protein extraction from neurotoxigenic Clostridium botulinum. AB - An acetone-sodium dodecyl sulfate disruption method was used for the extraction of cellular proteins from neurotoxigenic Clostridium botulinum. The amount of protein extracted per gram of dry weight and the protein profile as revealed by polyacrylamide gel electrophoresis was comparable to the extracts prepared by established methods, namely, sonication or agitation with beads. This method allows safer handling of C. botulinum by avoiding mechanical disruption, the generation of aerosols, and contamination of the apparatus. PMID- 22044263 TI - Congenital hair loss disorders: rare, but not too rare. AB - The mammalian hair follicle (HF) is an active skin appendage which operates hair cycles throughout life. Recent advances in molecular genetics have led to the identification of many genes expressed in the HF. Furthermore, mutations in some of these genes have been shown to underlie congenital hair loss disorders in humans. Patients with congenital hair loss disorders can show various hair shaft anomalies, such as woolly hair and monilethrix. In the Japanese populations, most patients with congenital woolly hair/hypotrichosis possess common founder mutations in the lipase H (LIPH) gene. Identification of the causative genes for hair loss disorders directly demonstrates crucial roles of these genes in HF morphogenesis, development and/or hair growth in humans. PMID- 22044264 TI - Improving proteomics mass accuracy by dynamic offline lock mass. AB - Several methods to obtain low-ppm mass accuracy have been described. In particular, online or offline lock mass approaches can use background ions, produced by electrospray under ambient conditions, as calibrants. However, background ions such as protonated and ammoniated polydimethylcyclosiloxane ions have relatively weak and fluctuating intensity. To address this issue, we implemented dynamic offline lock mass (DOLM). Within every MS1 survey spectrum, DOLM dynamically selected the strongest n background ions for statistical treatments and m/z recalibration. We systematically optimized the mass profile abstraction method to find one single m/z value to represent an ion and the number of calibrants. To assess the influence of the intensity of the analyte ions, we used tandem mass spectroscopy (MS/MS) datasets obtained from MudPIT analyses of two protein samples with different dynamic ranges. DOLM outperformed both external mass calibration and offline lock mass that used predetermined calibrant ions, especially in the low-ppm range. The unique dynamic feature of DOLM was able to adapt to wide variations in calibrant intensities, leading to averaged mass error center at 0.03 +/- 0.50 ppm for precursor ions. Such consistently tight mass accuracies meant that a precursor mass tolerance as low as 1.5 ppm could be used to search or filter post-search DOLM-recalibrated MS/MS datasets. PMID- 22044265 TI - Tooth-related risk factors for tooth loss in community-dwelling elderly people. AB - OBJECTIVE: To appropriately explore risk factors for tooth loss operating at the tooth-level, subject-related factors and a hierarchical data structure have to be considered. The purpose of this study was to evaluate tooth-related and subject related risk factors affecting tooth loss. METHODS: A 10-year longitudinal survey was carried out on 286 elderly subjects. At baseline, the prosthodontic status and abutment function of the 5574 teeth were recorded. Tooth loss was defined as the main outcome variable, and a multilevel logistic regression model considering subject and tooth levels was applied. RESULTS: Tooth loss was found in 75% of subjects and most frequently in molars. A multivariable, multilevel logistic regression revealed that the following tooth-related variables were significantly related to tooth loss over 10 years: maxillary teeth, multirooted teeth, single crowns, abutment teeth for a fixed/removable partial denture (FPD/RPD), and periodontally involved teeth. Among them, single crowns, abutment teeth for an FPD, and teeth with severe periodontal disease at baseline had the highest odds of 5.1, 6.0, and 7.1, respectively. CONCLUSIONS: The findings of this study suggest that tooth loss is the result of complex interactions of tooth-related factors. Several tooth-related variables including multirooted teeth, abutments, and single crowns were found to be possible risk factors for tooth loss. Thus, these findings confirm and underline the potential benefit of minimizing prosthetic treatment of molars. PMID- 22044267 TI - A pattern recognition method for lattice distortion measurement from HRTEM images. AB - The idea of the method is to analyse a crystal lattice by creating a grid of quadrilaterals corresponding to repeated cells that are visible in the image. This approach combines image processing elements with a continuum field theory, to create a distortion-independent similarity measure that is used to select the most appropriate among possible lattice configurations. Subsequently, displacement and distortion fields are computed from individual cell positions. The method allows one to obtain these fields even for images where a periodic cell does not necessarily appear as a single dot of intensity in a high resolution transmission electron microscopy (HRTEM) image, which results in a lower accuracy of commonly used approaches, namely geometric phase and peak finding. The results obtained from this method are verified quantitatively by comparison with known distortion tensor distributions and Burgers vector values on both simulated and real images. PMID- 22044266 TI - Targeting cell surface alpha(v)beta(3) integrin increases therapeutic efficacies of a legumain protease-activated auristatin prodrug. AB - Novel monomethylauristatin E (MMAE) prodrug 8 was designed and prepared that bound cell surface glycoprotein integrin alphavbeta3, and was activated using legumain protease as a catalyst. Upon activation, prodrug 8 strongly induced the death of MDA-MB-435 cells that express integrin alphavbeta3 on cell surface. Efficacies of prodrug 8 were also determined in vivo using animal models of 4T1 murine breast cancer, D121 Lewis lung carcinoma, and MDA-MB-435 human breast cancer. The results demonstrated that prodrug 8 decreased tumor growth and metastasis effectively. In comparison to the parent cytotoxin, MMAE, and prodrug 3, prodrug 8 was less toxic to mouse white blood cells. The latter caused no loss in weight gain of mice at a dose 3 mg/kg, which is over 30 times in excess to MMAE (0.1 mg/kg). We hypothesize that overexpression and colocalization of integrin alphavbeta3 and legumain protease on tumor cells, tumor vasculature, and/or tumor microenvironments can be exploited to enhance the efficacy and selectivity of potent cytotoxins, such as MMAE, which is otherwise too toxic to use for therapy. PMID- 22044268 TI - Thermodynamic analysis of protegrin-1 insertion and permeation through a lipid bilayer. AB - Molecular dynamics (MD) simulations are used to study the pathway for the insertion of the cationic antimicrobial peptide protegrin-1 (PG1) into mixed anionic lipid bilayers composed of palmitoyl-oleoyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine (POPE) in a 1:3 ratio (POPG/POPE). We calculate the potential of mean force (PMF) during the transfer of the peptide from the bulk aqueous phase to the transmembrane (TM) configuration using the adaptive biasing force (ABF) method. We find that the PMF has two energy minima separated by an energy barrier. One minimum corresponds to the fully transmembrane inserted state, with a free energy of -20.1 kcal/mol. The second PMF minimum, which corresponds to adsorption to the membrane surface, has a value of -2.5 kcal/mol. The PMF also shows the existence of a free energy barrier of +6.3 kcal/mol for the insertion process. Using the Kramers theory Langevin equation and the Grote-Hynes theory generalized Langevin equation, we calculated the transmission coefficient for PG1 diffusion through the potential barrier. We focus on the use of the PMF and the time correlation function of the fluctuation of the instantaneous force to calculate the rate constants for insertion/deinsertion of PG1 from the mixed POPG/POPE membrane. The influence of the activation free energy barrier on the dynamics of the insertion and permeation of peptides through the membrane are discussed. PMID- 22044269 TI - The impact of nontraditionalism on the malleability of gender stereotypes in Spain and Germany. AB - Gender stereotypes and inequalities are based on and sustained by people's perception of gender roles. The evolution of these gender roles, however, might be substantially different depending on cultural and social evolution in different countries. In a study, we investigated stereotypes in Germany and Spain, where residents might have different beliefs about gender roles due to their different social evolution after the Second World War and their economic and social advances. Results showed that in both countries people's expectations of differences in masculine characteristics between men and women were less noticeable than perceptions in the past or present. We also demonstrated that people perceive an increase in masculinity in women. This increase is more evident in Spaniards than in Germans. In estimations about the past, present, and future, Spaniards also perceived an increase of gender-stereotypic feminine characteristics more in men than in women. Our results are consistent with the predictions of social role theory, as gender stereotypes can include dynamic aspects and the content of these stereotypes is rooted in social roles. PMID- 22044270 TI - Voters and leaders in the mirror of politics: similarity in personality and voting choice in Italy and Spain. AB - Relations between voting choice and similarity in traits between voters and political candidates are examined in two studies. The first study was conducted in Spain, where the personalities of Mariano Rajoy and Jose Luis Rodriguez Zapatero were assessed. The second study was conducted in Italy, where the politicians assessed were Walter Veltroni and Silvio Berlusconi. Results show in both cases a similarity between voters' self-reported personality and their appraisals of the leaders of the party for which they voted. Similarity is generally higher with respect to traits that are the most distinctive for each platform and its leader. The findings show a higher similarity between voters and their leaders on the markers of agreeableness, such as "loyal" and "sincere." Findings hold across countries and political figures, demonstrating the role that personal characteristics of both voters and candidates play in orienting political preference. PMID- 22044271 TI - Relationships between in-role performance and individual values, commitment, and organizational citizenship behavior among Israeli teachers. AB - This study examines the relationship between (1) individual values, (2) organizational and occupational commitment, and (3) organizational citizenship behavior (OCB) and in-role performance in a sample of 192 teachers employed in 10 secular Jewish schools (response rate of 64%). The results showed that individual values were related to all commitment forms examined here, but contrary to expectations, there was no clear distinction between values that represent conservation and self-transcendence and values that represent openness to change and self-enhancement in terms of their relationship either to commitment or to behavioral outcomes. Likewise, there was no clear distinction between the three dimensions of commitment (affective, continuance, and normative) or two commitment foci (organizational and occupational) in terms of their relationships to different values. Unsurprisingly, the findings showed a strong effect of commitment on OCB and in-role performance. The findings show that both individual values and commitment are concepts that can increase our understanding of employees' behavior in the workplace. We conclude by emphasizing the need for further research on the relationship between values, commitment, and performance and by suggesting some directions for such research. PMID- 22044272 TI - Psychosocial correlates of internet use among Italian students. AB - Davis (2001) introduced a cognitive-behavioral theory of generalized pathological internet use (GPIU) that attempts to model the etiology, development, and outcomes associated with PIU. According to this model, pre-existing psychosocial problems (depression, loneliness, or low levels of social support) predispose an individual to GPIU cognitions, behaviors, and negative outcomes. An exploratory study intended to investigate whether GPIU is associated with psychosocial health (loneliness, depression, self-esteem, and shyness), also taking account of types of internet services used, was conducted in a sample of Italian undergraduate students. A cross-sectional and descriptive correlational design was used. The participants were 157 undergraduate students (34 male and 123 female) enrolled at The University of Florence. The results revealed a stronger correlation between the frequency of use of communicative services (as opposed to leisure or informational services) and GPIU levels. Among services, the most significant predictor of GPIU was the frequency of use of chat rooms and "adult" websites. All psychosocial health variables were correlated with GPIU, with the exception of shyness; however, general loneliness was the only significant predictor of GPIU. Depression and self-esteem were not significant predictors of GPIU. These results are consistent with the assumption that GPIU is related to the social aspect of the internet (e.g., online chatting) and arises from the unique communicative environment found online. In accordance with recent studies, social wellbeing (i.e. loneliness) seems to play a greater role than psychological health in deriving negative effects from internet use. PMID- 22044273 TI - Gender stereotypes in management: a comparative study of communist and postcommunist Romania. AB - This study sets out to investigate the changes in the perception of women in leading positions in communist and postcommunist Romania. The study uses a noninvasive paradigm of analyzing the content of obituaries for women and men in leading positions published in a national journal, and shows that the gender gap in management widened during the postcommunist period. In postcommunist Romania, women are perceived as being less able to lead/manage and more relational in their leadership style as compared to men, while in the communist period the gender differences were not significant. PMID- 22044274 TI - Tell me who you are and I tell you how you feel: expected emotional reactions to success and failure are influenced by knowledge about a person's personality. AB - The present research investigated the influence of knowledge about a person's modesty or arrogance on people's expectations regarding that person's emotional reactions to success and failure. Arrogance and modesty reflect the extent to which someone is likely to publicize their ability. Accordingly, we predicted that observers' expectations regarding a person's tendency to publicize their ability should inform expectations about the person's emotional reactions to success and failure. In two vignette studies, observers predicted the emotional state of a protagonist, as well as the probability that s/he will actually express that emotion and share the experience with others. For success, participants predicted a protagonist's pride, happiness, schadenfreude, and embarrassment if praised for a positive outcome. For failure, participants predicted anger, shame, guilt, sadness, and fear reactions. Across studies, personality information explained more variance than did gender or status. Results showed that the expectations for an arrogant person matched modal expectations for success, whereas for failure the expectations for the modest individual were closest to the modal expectations. Specifically, both modest and arrogant individuals were expected to suppress emotions that do not fit their self-presentational styles rather than to exaggerate expressions that do. This paper adds to our understanding of the information that people use to predict others' emotional reactions. PMID- 22044275 TI - Antibonding plasmon modes in colloidal gold nanorod clusters. AB - The optical response of nanoplasmonic colloids in disperse phase is strictly related to their shape. However, upon self-assembly, new optical features, for example, bonding or antibonding modes, emerge as a result of the mutual orientations of nanoparticles. The geometry of the final assemblies often determines which mode is dominating in the overall optical response. These new plasmon modes, however, are mostly observed in silico, as self-assembly in the liquid phase leads to cluster formation with a broad range of particle units. Here we show that low-symmetry clustering of gold nanorods (AuNRs) in solution can also reveal antibonding modes. We found that UV-light irradiation of colloidal dispersions of AuNRs in N-methyl-2-pyrrolidone (NMP), stabilized by poly(vinylpyrrolidone) (PVP) results in the creation of AuNRs clusters with ladderlike morphology, where antibonding modes can be identified. We propose that UV irradiation induces formation of radicals in solvent molecules, which then promote cross-linking of PVP chains on the surface of adjacent particles. This picture opens up a number of relevant questions in nanoscience and is expected to find application in light induced self-assembly of particles with various compositions and morphologies. PMID- 22044278 TI - Semisynthesis and biological evaluation of ganodermanontriol and its stereoisomeric triols. AB - The first synthesis of ganodermanontriol, a bioactive lanostane triterpene from the medicinal mushroom Ganoderma lucidum, has been achieved in 15.3% yield over nine steps, along with its three stereoisomeric triols and ganoderol A. The key steps leading to this family of isomers involve the reconstruction of the trisubstituted alkene by stereoselective and chemoselective phosphonate reactions and the formation of the unusual Delta7,9(11)-diene core by the mild acidic opening of a lanosterone-derived epoxide. Ganodermanontriol showed promising activity on the inhibition and proliferation of breast cancer cells. The effect of ganodermanontriol and its isomers on cell proliferation was assayed; IC50 values of 5.8 and 9.7 MUM on breast cancer cell lines MCF-7 and MDA-MB-231, respectively, were found for ganodermanontriol. PMID- 22044279 TI - Exergy efficiency in industry: where do we stand? AB - Efficiency is a term generally used to determine how well a system performs. However, efficiency can have different meanings and, unaccompanied by a formal definition or taken out of context, can lead to serious misconceptions. In many official publications, efficiency is calculated as the ratio of useful output to energy input. This measure reflects the first law of thermodynamics (conservation of energy) but does not reflect the potential for improvement. A better measure, that also reflects the second law of thermodynamics, is the ratio of the potential useful (exergy) output to the potential useful (exergy) input. We estimate second law efficiencies for the inorganic and organic chemical industries to be 29% and 35% respectively. We also estimate the efficiency of the U.S. industry sector as a whole to be 37.6%, as compared to only 7.7% for the overall U.S. economy. These figures are far lower than the "first law" figures published by the U.S. Department of Energy (80% for industry and 42.5% overall) and they imply a significant potential for improvement. PMID- 22044277 TI - Regulation of CD4+ T-cell polarization by suppressor of cytokine signalling proteins. AB - Suppressors of cytokine signalling (SOCS) proteins are induced in responses to many stimuli and by binding to cytokine receptors and associated janus kinase (JAK) proteins, directly regulate the activation of the signal transducers and activators of transcription (STATs). STAT proteins regulate the expression of many genes required for the differentiation of various CD4(+) T helper cell lineages, and there is now accumulating evidence that SOCS also play essential roles in the regulation and maintenance of CD4(+) T-cell polarization. As it is now clear that CD4(+) T cells are more plastic than initially thought, it is of particular importance to understand the molecular mechanisms regulating CD4(+) T cell differentiation. Here we review the current understanding of how STATs and SOCS act in concert to influence the polarization of CD4(+) T cells and highlight the relevance of this in disease. PMID- 22044276 TI - Nutrition, epigenetics, and metabolic syndrome. AB - SIGNIFICANCE: Epidemiological and animal studies have demonstrated a close link between maternal nutrition and chronic metabolic disease in children and adults. Compelling experimental results also indicate that adverse effects of intrauterine growth restriction on offspring can be carried forward to subsequent generations through covalent modifications of DNA and core histones. RECENT ADVANCES: DNA methylation is catalyzed by S-adenosylmethionine-dependent DNA methyltransferases. Methylation, demethylation, acetylation, and deacetylation of histone proteins are performed by histone methyltransferase, histone demethylase, histone acetyltransferase, and histone deacetyltransferase, respectively. Histone activities are also influenced by phosphorylation, ubiquitination, ADP ribosylation, sumoylation, and glycosylation. Metabolism of amino acids (glycine, histidine, methionine, and serine) and vitamins (B6, B12, and folate) plays a key role in provision of methyl donors for DNA and protein methylation. CRITICAL ISSUES: Disruption of epigenetic mechanisms can result in oxidative stress, obesity, insulin resistance, diabetes, and vascular dysfunction in animals and humans. Despite a recognized role for epigenetics in fetal programming of metabolic syndrome, research on therapies is still in its infancy. Possible interventions include: 1) inhibition of DNA methylation, histone deacetylation, and microRNA expression; 2) targeting epigenetically disturbed metabolic pathways; and 3) dietary supplementation with functional amino acids, vitamins, and phytochemicals. FUTURE DIRECTIONS: Much work is needed with animal models to understand the basic mechanisms responsible for the roles of specific nutrients in fetal and neonatal programming. Such new knowledge is crucial to design effective therapeutic strategies for preventing and treating metabolic abnormalities in offspring born to mothers with a previous experience of malnutrition. PMID- 22044281 TI - Low-cost aerosol exposure system for Guinea pigs. AB - BACKGROUND: This project designed and tested an economical apparatus to safely expose guinea pigs to biohazardous aerosol. The goals were to design a system that can be easily decontaminated, fits in a biosafety cabinet, and affordable. METHODS: It is composed of three main chambers housed in an outer box that fits within a conventionally sized biosafety cabinet. The animal chamber contains a removable housing unit for either four or eight guinea pigs. The aerosol chamber is separate to minimize contamination. The nebulizer chamber is also sealed to reduce risks from leakages. This apparatus is easily decontaminated by immersion in disinfectant. RESULTS AND CONCLUSIONS: This system has been tested for safety, ergonomics, efficiency of rodent exposure to bacteria, airflow, access points, seal mechanisms, and size. This system is effective, consistent, safe and cost efficient. PMID- 22044280 TI - Diversity of Chlamydomonas channelrhodopsins. AB - Channelrhodopsins act as photoreceptors for control of motility behavior in flagellates and are widely used as genetically targeted tools to optically manipulate the membrane potential of specific cell populations ("optogenetics"). The first two channelrhodopsins were obtained from the model organism Chlamydomonas reinhardtii (CrChR1 and CrChR2). By homology cloning we identified three new channelrhodopsin sequences from the same genus, CaChR1, CyChR1 and CraChR2, from C. augustae, C. yellowstonensis and C. raudensis, respectively. CaChR1 and CyChR1 were functionally expressed in HEK293 cells, where they acted as light-gated ion channels similar to CrChR1. However, both, which are similar to each other, differed from CrChR1 in current kinetics, inactivation, light intensity dependence, spectral sensitivity and dependence on the external pH. These results show that extensive channelrhodopsin diversity exists even within the same genus, Chlamydomonas. The maximal spectral sensitivity of CaChR1 was at 520 nm at pH 7.4, about 40 nm redshifted as compared to that of CrChR1 under the same conditions. CaChR1 was successfully expressed in Pichia pastoris and exhibited an absorption spectrum identical to the action spectrum of CaChR1 generated photocurrents. The redshifted spectra and the lack of fast inactivation in CaChR1- and CyChR1-generated currents are features desirable for optogenetics applications. PMID- 22044283 TI - Role of alpha1- and alpha2-GABA(A) receptors in mediating the respiratory changes associated with benzodiazepine sedation. AB - BACKGROUND AND PURPOSE: The molecular substrates underlying the respiratory changes associated with benzodiazepine sedation are unknown. We examined the effects of different doses of diazepam and alprazolam on resting breathing in wild-type (WT) mice and clarified the contribution of alpha1- and alpha2-GABA(A) receptors, which mediate the sedative and muscle relaxant action of diazepam, respectively, to these drug effects using point-mutated mice possessing either alpha1H101R- or alpha2H101R-GABA(A) receptors insensitive to benzodiazepine. EXPERIMENTAL APPROACH: Room air breathing was monitored using whole-body plethysmography. Different groups of WT mice were injected i.p. with diazepam (1 100 mg.kg(-1) ), alprazolam (0.3, 1 or 3 mg.kg(-1) ) or vehicle. alpha1H101R and alpha2H101R mice received 1 or 10 mg.kg(-1) diazepam or 0.3 or 3 mg.kg(-1) alprazolam. Respiratory frequency, tidal volume, time of expiration and time of inspiration before and 20 min after drug injection were analysed. KEY RESULTS: Diazepam (10 mg.kg(-1) ) decreased the time of expiration, thereby increasing the resting respiratory frequency, in WT and alpha2H101R mice, but not in alpha1H101R mice. The time of inspiration was shortened in WT and alpha1H101R mice, but not in alpha2H101R mice. Alprazolam (1-3 mg.kg(-1) ) stimulated the respiratory frequency by shortening expiration and inspiration duration in WT mice. This tachypnoeic effect was partially conserved in alpha1H101R mice while absent in alpha2H101R mice. CONCLUSIONS AND IMPLICATIONS: These results identify a specific role for alpha1-GABA(A) receptors and alpha2-GABA(A) receptors in mediating the shortening by benzodiazepines of the expiratory and inspiratory phase of resting breathing respectively. PMID- 22044284 TI - Onset of hydrogen bonded collective network of water in 1,4-dioxane. AB - We have studied the evolution of water hydrogen bonded collective network dynamics in mixtures of 1,4-dioxane (Dx) as the mole fraction of water (X(w)) increases from 0.005 to 0.54. The inter- and intramolecular vibrations of water have been observed using terahertz time domain spectroscopy (THz-TDS) in the frequency range 0.4-1.4 THz (13-47 cm(-1)) and Fourier transform infrared (FTIR) spectroscopy in the far-infrared (30-650 cm(-1)) and mid-infrared (3000-3700 cm( 1)) regions. These results have been correlated with the reactivity of water in these mixtures as determined by kinetic studies of the solvolysis reaction of benzoyl chloride (BzCl). Our studies show an onset of intermolecular hydrogen bonded water network dynamics beyond X(w) >= 0.1. At the same concentration, we observe a rapid increase of the rate constant of solvolysis of BzCl in water-Dx mixtures. Our results establish a correlation between the onset of collective hydrogen bonded network with the solvation dynamics and the activity of clustered water. PMID- 22044285 TI - 1,25-Dihydroxyvitamin D3 inhibits proliferation but not the suppressive function of regulatory T cells in the absence of antigen-presenting cells. AB - Vitamin D3 is known to induce regulatory T (Treg) cells by rendering antigen presenting cells tolerogenic, its direct effect on human naturally occurring Treg cells is unclear. Here, we investigated if and how 1,25-dihydroxyvitamin D(3) [1,25(OH)2D3] can directly affect the proliferation and function of human naturally occurring Treg cells in vitro. First, we demonstrated that these Treg cells express vitamin D receptors that were up-regulated following anti-CD3/CD28 bead stimulation. 1,25(OH)2D3 inhibited proliferation of Treg cells even when exogenous interleukin-2 was provided. Treg cells were more susceptible to the inhibitory effect of 1,25(OH)2D3 than conventional T cells(.) 1,25(OH)2D3 neither affected the anergic state nor the suppressive function of Treg cells but induced a subtle increase in interleukin-10-secreting cells. The cell-division-inhibiting effect of 1,25(OH)2D3 on Treg cells was also demonstrated in vivo by supplementing vitamin D-deficient HIV-1-infected patients with 2000 IU cholecalciferol (vitamin D3). Increased serum 1,25(OH)2D3 levels were associated with a drop in the number and percentage of Treg cells, which may be attributed to a decrease in the proliferating Foxp3+ Treg cell population. In conclusion, 1,25(OH)2D3 directly affects Treg cell growth and promotes interleukin-10 production without apparent effects on activation status and suppressive phenotype whereas in vivo, high serum 1,25(OH)2D3 levels are associated with reduced Treg cell proliferation and a reduced number of Treg cells. PMID- 22044286 TI - Skin manifestations associated with chemotherapy in children with hematologic malignancies. AB - Chemotherapy used in the treatment of malignancies produces multiple mucocutaneous adverse reactions that may be clinically challenging. These mucocutaneous reactions are common and sometimes not diagnosed. The objective of this study was to determine the clinical patterns of the mucocutaneous manifestations during and after chemotherapy in children with a hematologic malignancy and to determine whether nutritional status influences the clinical presentation. We recruited patients aged 6 months to 16 years diagnosed with leukemia and lymphoma from a pediatric hematology outpatient clinic between November 2008 and May 2010. The patients were divided into two groups: Group 1, recently diagnosed patients, included in the study before receiving chemotherapy, and Group 2, patients in surveillance who had not had chemotherapy for at least 3 months. A dermatologic examination was performed, and biopsy and mycological and bacteriological tests were conducted if necessary, with 6 months of follow-up. We evaluated 89 patients and included 65 in the study: 40 boys and 25 girls with an average age of 8.3 years. All patients had skin lesions at some time during their baseline assessment or follow-up. The manifestations found were anagen effluvium, xerosis, and acral hyperpigmentation. To our knowledge, this is the first comparative study of skin manifestations associated with chemotherapy in a Mexican pediatric population. The mucocutaneous manifestations associated with chemotherapy are important causes of morbidity. All of the children in our study had skin lesions on assessment. We did not find an association between skin manifestations and nutritional status. PMID- 22044287 TI - S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial. AB - BACKGROUND: S-adenosyl-L-methionine (SAM) is the methyl donor for all methylation reactions and regulates the synthesis of glutathione, the main cellular antioxidant. Previous experimental studies suggested that SAM may benefit patients with established alcoholic liver diseases (ALDs). The aim of this study was to determine the efficacy of SAM in treatment for ALD in a 24-week trial. The primary endpoints were changes in serum aminotransferase levels and liver histopathology scores, and the secondary endpoints were changes in serum levels of methionine metabolites. METHODS: We randomized 37 patients with ALD to receive 1.2 g of SAM by mouth or placebo daily. Subjects were required to remain abstinent from alcohol drinking. A baseline liver biopsy was performed in 24 subjects, and a posttreatment liver biopsy was performed in 14 subjects. RESULTS: Fasting serum SAM levels were increased over timed intervals in the SAM treatment group. The entire cohort showed an overall improvement of AST, ALT, and bilirubin levels after 24 weeks of treatment, but there were no differences between the treatment groups in any clinical or biochemical parameters nor any intra- or intergroup differences or changes in liver histopathology scores for steatosis, inflammation, fibrosis, and Mallory-Denk hyaline bodies. CONCLUSIONS: Whereas abstinence improved liver function, 24 weeks of therapy with SAM was no more effective than placebo in the treatment for ALD. PMID- 22044288 TI - Prevalence of Listeria monocytogenes, Vibrio parahaemolyticus, Staphylococcus aureus, and Salmonella spp. in seafood products using multiplex polymerase chain reaction. AB - Although several etiological agents can be transmitted through seafood consumption, Listeria monocytogenes, Vibrio parahaemolyticus, Staphylococcus aureus, and Salmonella spp. are considered among the most important pathogens in terms of public health and disease. In this study, multiplex polymerase chain reaction (PCR), as a rapid and cost-effective method, was used to determine the prevalence of these pathogens in 245 samples of raw/fresh, frozen, and ready-to eat (RTE) seafood products marketed in Iran. The prevalence of L. monocytogenes in raw/fresh fish and shrimp samples was 1.4%, whereas 2.9% of the raw/fresh fish and 7.1% of the shrimp samples were contaminated with V. parahaemolyticus. No contamination with L. monocytogenes and V. parahaemolyticus was found in frozen and RTE seafood products. The prevalence of S. aureus was found to be higher than other investigated pathogens. S. aureus was detected in 5% of the raw/fresh samples of fish and shrimp, 17.5% of the frozen, and 12.3% of the RTE samples. Further, our findings indicate that 2.9% of the fish samples, 4.3% of the shrimp samples, and 1.5% of the RTE samples were contaminated with Salmonella spp. Owing to the potential hazard of these pathogenic bacteria, multiplex PCR can provide a rapid and cost-effective method for the surveillance of these pathogens in seafood products. PMID- 22044289 TI - Antimicrobial susceptibility testing and genotypic characterization of Staphylococcus aureus from food and food animals. AB - Staphylococcus aureus is commonly present in humans and animals. The aim of this study was to investigate antimicrobial resistance and genetic characteristics of S. aureus from food and food animals in Shaanxi Province in China. A total of 332 nasal swabs, breast skin swabs, raw milk, and pork samples were collected from local pig, dairy farms, or local grocery stores and screened for the presence of S. aureus. S. aureus isolates were characterized using antimicrobial susceptibility, pulsed-field gel electrophoresis (PFGE) analysis, and polymerase chain reaction for detecting pvl and mecA genes. Methicillin-resistant S. aureus (MRSA) strains were additionally tested for SCCmec type and exfoliative toxin genes. The prevalence of S. aureus was 30.6% in pig nasal swabs, 32.5% in pork, 25.7% in cow nasal swabs, 30.8% in cow breast skin swabs, and 29.3% in milk samples. Resistances were common among isolates tested against erythromycin (65.7%), tetracycline (65.7%), ciprofloxacin (52.7%), followed by gentamicin (36.7%), chloramphenicol (23.1%), cefoxitin (8.3%), and oxacillin (7.7%), but no isolate was resistant to vancomycin, amikacin, or cefoperazone. pvl gene was found in the isolates from all types of samples except from cow nasal swabs. Fourteen isolates from pig nasal swabs contained mecA gene and were considered as MRSA. PFGE analysis showed that nasal isolates differed from food isolates, but isolates from the same animal source appeared to cluster closely. The PFGE patterns of MRSA isolates were different from other S. aureus isolates from pig nasal cavity even though they were from the same source. All the MRSA isolates belonged to SCCmec type IV(b). No isolates contained exfoliative toxin genes. These findings indicated that S. aureus, including multidrug-resistant S. aureus, are widely spread in food animals and animal-derived foods in Shaanxi Province, China. MRSA isolates from pigs may pose potential health risks for workers in swine farms and the community at large. PMID- 22044291 TI - Measuring motivation in swine: the food-metric scale. AB - Understanding how nonhuman animals such as swine respond to their environment and understanding how to provide them with a good quality of life involves using a range of experimental approaches. More and more, ethological researchers are turning to operant methods to answer some of these questions. Employing an operant such as a lever, researchers can assess how hard animals will work to get access to environmental resources: increased space or social contact. It is difficult, however, to determine how the effort made by the animals relates to the degree to which they need the resource and, in particular, how to interpret intermediate levels of responding. One approach to understanding the level of need is to compare it with familiar states of deprivation such as hunger. Food is an environmental resource known to range from low to high value depending on deprivation level. Depriving animals of a fixed proportion of their daily ad libitum intake allows the animals to demonstrate the levels of responding produced at satiation: 23 hr deprivation and a range of intermediate points. The resulting scale has both empirical and intuitive value and can help in understanding the value of various degrees of operant effort. Ultimately, this information will help in deciding which environmental conditions should be provided to swine as part of routine husbandry. PMID- 22044292 TI - Training large macaws for artificial insemination procedures. AB - For some endangered parrot species, captive breeding may be the only insurance for their survival. However, many individuals in captivity do not reproduce. Artificial insemination (AI) may help overcome reproductive failures or geographic distance. For semen collection in birds, massage is the most commonly used method. However, this process, which usually requires capture and restraint, involves risk of stress and injuries. The aim of this experiment was to train large macaws to accept the physical manipulations of their body parts needed for the artificial insemination process. Within 15 weeks, a male and a female Buffon's macaw (Ara ambiguus) learned to accept handling without apparent stress. A pair of green-winged macaws (Ara chloropterus) progressed more slowly and displayed some signs of stress. This stress highlights the need to monitor the birds' possible signs of discomfort during the training in order to adapt the working protocol. These results demonstrate that it is possible to train the AI behaviors, thus avoiding the capture, restraint, and anesthesia. An added benefit to this is the potential for the training to provide a form of behavioral enrichment. PMID- 22044293 TI - Is it a good idea to train fillies and colts separately? AB - This study compared the physiological response to novel situations in sex separated and sex-mixed groups of horses, as measured by heart rate (HR). The study evaluated the possibility of training horses in a mixed-sex system. The study included 41 Purebred Arabian 21/2-year-olds during their first walk on an automated horse walker. Four groups, divided by manner of care and training, consisted of 10 colts and 10 fillies kept in separate stables and trained in separate male or female groups and 12 colts and 9 fillies kept in the same stable and trained together. The study measured HR when horses were at rest before exercise, while moving from stable to walker, during 30 min of exercise on walker, while moving from walker to stable, and at rest after exercise. Mean HR scores recorded from training on the walker were higher in sex-mixed groups. Results obtained while horses were moving from stable to walker, then from walker to stable, were significantly higher in the sex-mixed groups. The study did not recommend training young horses in sex-mixed groups. PMID- 22044294 TI - Using fecal hormonal and behavioral analyses to evaluate the introduction of two sable antelope at Lincoln Park Zoo. AB - Introductions of sable antelope (Hippotragus niger) can be difficult due to the potential ensuing aggression compounded by their large horns. The goal was to use hormonal assays and behavioral analyses to evaluate the success of an introduction of 2 adult females at Lincoln Park Zoo. The objectives were to (a) document behavioral and hormonal changes in 2 female sable antelope during the introduction, (b) compare fecal glucocorticoid metabolites (FGM) in each individual during the introduction stages, (c) measure fecal androgen metabolites (FAM) during introduction and compare with dominance rank and observed aggression, and (d) monitor estrous cycle synchronization. Results demonstrate that FGM were higher before than during and after the introduction. Behavioral observations indicated limited aggression between females, although the keeper survey results revealed that the new female was more dominant and had higher mean FGM and FAM than the resident. Both sable antelope were reproductively active throughout the year. Results indicate that fecal hormone analysis can provide zoo management with valuable information to minimize the risk of aggression, injury, and stress during introductions of nonhuman animals. PMID- 22044295 TI - Influence of cinnamon and catnip on the stereotypical pacing of oncilla cats (Leopardus tigrinus) in captivity. AB - Nonhuman animals in captivity can experience environmental privation that results in their exhibiting abnormal behaviors. Environmental enrichment techniques can help improve their welfare. This study investigated the behavior of 8 zoo-housed oncilla cats (Leopardus tigrinus) in response to 2 odors (catnip and cinnamon) introduced individually into the animals' enclosures for 3 consecutive days. Proportion of scans spent engaging in stereotypical pacing were compared before, during, and after treatments. The addition of cinnamon reduced the proportion of pacing during and after enrichment (Wilcoxon: Z = 3.16, p < .001; Z = 3.16, p < .001, respectively), indicating a prolonged effect of the enrichment on the animals' behavior. Catnip appears to have elicited no significant difference in the stereotypic pacing before, during, or after the enrichment (Friedman: X(2) = 2.69; p = .260). The results highlight the potential use of cinnamon as a method of environmental enrichment for small captive-housed cats. PMID- 22044296 TI - Welfare assessments based on lifetime health and production data in Danish dairy cows. AB - The objective of this study was to describe how information about the whole lifetime of the cow can be used when defining nonhuman animal-based criteria of the welfare of animals on the farm. Often measured over a short period, disease occurrence provides information relevant for assessing the current welfare state of the herd. Arguably, however, if disease records are to be used as ethically relevant welfare indicators, it is also important to record disease occurrence over the individual animal's entire life span. Thus, it matters ethically whether the burden of an outbreak of disease or other condition affecting animal welfare is carried by a few individuals or is distributed more evenly. To illustrate this principle, the study obtained data on disease treatment records and production from 392,287 cows from the Danish Cattle Database. The average cow had lived for 5 years and produced more than 22,000 L of milk. The medium number of treatments a cow had received for any disease was 2, but 10% of the cows had received more than 8 treatments for a disease. The study concluded that lifetime description provides a measure of disease occurrence that gives added value of ethical relevance to single-point prevalence or short-term incidence. PMID- 22044300 TI - Growth of mesoporous silica nanoparticles monitored by time-resolved small-angle neutron scattering. AB - Since the first development of surfactant-templated mesoporous silicas, the underlying mechanisms behind the formation of their structures have been under debate. Here, for the first time, time-resolved small-angle neutron scattering (tr-SANS) is applied to study the complete formation of mesoporous silica nanoparticles. A distinct advantage of this technique is the ability to detect contributions from the whole system, enabling the visualization not only of particle genesis and growth but also the concurrent changes to the coexistent micelle population. In addition, using contrast-matching tr-SANS, it is possible to highlight the individual contributions from the silica and surfactant. An analysis of the data agrees well with the previously proposed "current bun" model describing particle growth: Condensing silica oligomers adsorb to micelles, reducing intermicellar repulsion and resulting in aggregation to form initial particle nuclei. From this point, the growth occurs in a cooperative manner, with condensing silica filling the gaps between further aggregating micelles. The mechanistic results are discussed with respect to different reaction conditions by changing either the concentration of the silica precursor or the temperature. In doing so the importance of in situ techniques is highlighted, in particular, tr-SANS, for mechanism elucidation in the broad field of materials science. PMID- 22044301 TI - Oxygen as a regulator of MA-10 cell functions: effect of cobalt chloride on vascular endothelial growth factor production. AB - Mammalian testis functions at a temperature and oxygen tension (pO(2)) lower than the core body. Hypoxia-inducible factor-1alpha (HIF-1alpha) mediates the adaptive responses to hypoxia such as production of angiogenic vascular endothelial growth factor (VEGF) in a variety of cells and tissues. VEGF production in Leydig cells is stimulated by luteinising hormone (LH)/cAMP. We have conducted experiments to find out whether HIF-1alpha is involved in LH/cAMP-induced secretion of VEGF by Leydig cell-derived MA-10 cells. Both cobalt chloride (CoCl(2)), an inducer of hypoxia, and 8-Br-cAMP enhanced HIF-1alpha activity followed by an increase in VEGF secretion. However, there was no change in mRNA levels of HIF-1alpha. Inhibition of HIF-1alpha activity by cyclosporine A (CsA) inhibited a rise in VEGF production in response to CoCl(2) as well as 8-Br-cAMP. Inhibitors of protein kinase A (PKA), extracellular regulated kinase 1/2 (ERK1/2) and phosphatidyl inositol-3 kinase/Akt (PI3-K/Akt) inhibited the increase in VEGF levels in response to both CoCl(2) and 8-Br-cAMP. The data suggest that HIF 1alpha is a mediator of hypoxia- as well as 8-Br-cAMP-stimulated production of VEGF in MA-10 cells; both the stimuli act through a common signalling cascade. PMID- 22044303 TI - Selective peroxisome proliferator-activated receptor-gamma modulation to reduce cardiovascular risk in patients with insulin resistance. AB - The thiazolidinediones (TZDs) rosiglitazone and pioglitazone improve glucose homeostasis through activation of peroxisome proliferator-activated receptor (PPAR)-gamma. Their use, however, has been limited due to adverse effects that include body weight gain and edema leading to congestive heart failure. Selective PPAR-gamma modulators (SPPARMs) are second generation PPAR-gamma ligands designed to improve insulin sensitivity with minimal undesirable effects associated with first generation PPAR-gamma agonists. INT131 is one of the first SPPARMs to reach human trials. Early phase human studies with INT131 look promising with changes in plasma lipids and glucose being equal or better than what is seen with rosiglitazone and pioglitazone treatment but without evidence of edema. This profile of improved glucose homeostasis, improved plasma lipids, and reduced inflammation in the absence of edema would be expected to reduce cardiovascular risk in patients with Type 2 diabetes mellitus. Recent patents of novel approaches for the use of PPAR-gamma related compounds with the potential for this improved risk-benefit ratio are discussed. PMID- 22044302 TI - Porous polymer monoliths functionalized through copolymerization of a C60 fullerene-containing methacrylate monomer for highly efficient separations of small molecules. AB - Monolithic poly(glycidyl methacrylate-co-ethylene dimethacrylate) and poly(butyl methacrylate-co-ethylene dimethacrylate) capillary columns, which incorporate the new monomer [6,6]-phenyl-C(61)-butyric acid 2-hydroxyethyl methacrylate ester, have been prepared and their chromatographic performance have been tested for the separation of small molecules in the reversed phase. While addition of the C60 fullerene monomer to the glycidyl methacrylate-based monolith enhanced column efficiency 18-fold, to 85,000 plates/m at a linear velocity of 0.46 mm/s and a retention factor of 2.6, when compared to the parent monolith, the use of butyl methacrylate together with the carbon nanostructured monomer afforded monolithic columns with an efficiency for benzene exceeding 110,000 plates/m at a linear velocity of 0.32 mm/s and a retention factor of 4.2. This high efficiency is unprecedented for separations using porous polymer monoliths operating in an isocratic mode. Optimization of the chromatographic parameters affords near baseline separation of 6 alkylbenzenes in 3 min with an efficiency of 64,000 plates/m. The presence of 1 wt % or more of water in the polymerization mixture has a large effect on both the formation and reproducibility of the monoliths. Other factors such as nitrogen exposure, polymerization conditions, capillary filling method, and sonication parameters were all found to be important in producing highly efficient and reproducible monoliths. PMID- 22044304 TI - Thrombolysis in ischemic stroke: focus on new treatment strategies. AB - Stroke is the third leading cause of death and the main cause of permanent disability in western countries. Reperfusion within 3 hours of symptoms-onset is the most beneficial of all therapeutic strategies for acute ischemic stroke. Alteplase has been the first thrombolytic treatment approved by FDA. However, its use is still limited to specific patient subgroups and may be complicated by severe side effects, including massive cerebral hemorrhages. This review is aimed at investigating the current and future treatment strategies in ischemic stroke, including new fibrinolytic drugs, sonothrombolysis, mechanical clot retrievals, and recent patents. PMID- 22044305 TI - The making of autobiographical memory: intersections of culture, narratives and identity. AB - Autobiographical memory is a uniquely human form of memory that integrates individual experiences of self with cultural frames for understanding identities and lives. In this review, we present a theoretical and empirical overview of the sociocultural development of autobiographical memory, detailing the emergence of autobiographical memory during the preschool years and the formation of a life narrative during adolescence. More specifically, we present evidence that individual differences in parental reminiscing style are related to children's developing autobiographical narratives. Parents who structure more elaborated coherent personal narratives with their young children have children who, by the end of the preschool years, provide more detailed and coherent personal narratives, and show a more differentiated and coherent sense of self. Narrative structuring of autobiographical remembering follows a protracted developmental course through adolescence, as individuals develop social cognitive skills for temporal understanding and causal reasoning that allows autobiographical memories to be integrated into an overarching life narrative that defines emerging identity. In addition, adolescents begin to use culturally available canonical biographical forms, life scripts, and master narratives to construct a life story and inform their own autobiographical narrative identity. This process continues to be socially constructed in local interactions; we present exploratory evidence that parents help adolescents structure life narratives during coconstructed reminiscing and that adolescents use parents and families as a source for their own autobiographical content and structure. Ultimately, we argue that autobiography is a critical developmental skill; narrating our personal past connects us to our selves, our families, our communities, and our cultures. PMID- 22044306 TI - The role of rehearsals in self-generated prospective memory tasks. AB - In order to inquire into the nature of retrieval in prospective memory in a naturalistic context, we investigated the number and circumstances of rehearsals of different kinds of intentions to be pursued during a single time period. Thirty-six students were given four minutes to generate a list of tasks they were planning to perform over the course of 10 days. During this retention interval, they were provided with pocket-size diaries in which they recorded the details of each occasion they thought about the tasks previously listed. As to the nature of any triggers or cues that prompted rehearsal, the participants were asked to choose one of three alternatives: (1) association with an internal or an external cue that accidently appeared in the surroundings (accidental rehearsals), (2) deliberate thinking, e.g. while planning (self-initiated rehearsals), (3) recollection that spontaneously popped into one's mind for no apparent reason (no trigger rehearsals). The results showed that thoughts about intended actions appeared more often after accidental cues than for no apparent reason. However, the relative contribution of self-initiated triggers to the rehearsal process was substantial: Most importantly, it was the self-initiated rehearsal that differentiated between executed and unexecuted actions. In addition, the most activated intention resulted in a higher frequency of no-trigger and self initiated rehearsals than the remaining intentions. Finally, perceived intention importance was positively related to both the number of rehearsals and the likelihood of successful task completion. The results are discussed with regard to which factors may be crucial for the successful performance of participants' own self-generated intentions in a natural setting. The role of deliberate rehearsal in specifying the details of the intended action and its designated retrieval context is highlighted. PMID- 22044307 TI - Hope in Africa?: social representations of world history and the future in six African countries. AB - Data on social representations of world history have been collected everywhere in the world except sub-Saharan Africa. Two studies using open-ended data involving university students from six African countries fill this gap. In Study 1, nominations from Cape Verde and Mozambique for the most important events in world history in the past 1000 years were dominated by war and politics, recency effects, and Western-centrism tempered by African sociocentrism on colonization and independence. The first three findings replicated previous research conducted in other parts of the world, but the last pattern contrasted sharply with European data. Study 2 employed a novel method asking participants how they would begin the narration of world history, and then to describe a major transition to the present. Participants most frequently wrote about the evolution of humanity out of Africa, followed by war and then colonization as a beginning, and then replicated previous findings with war, colonization, and technology as major transitions to the present. Finally, when asked about how they foresaw the future, many participants expressed hope for peace and cooperation, especially those facing more risk of collective violence (Burundi and Congo). A colonial/liberation narrative was more predominant in the data from former Portuguese colonies (Angola, Cape Verde, and Guinea-Bissau) than from former Belgian colonies (Burundi and Congo). PMID- 22044308 TI - Japanese children's amae and mothers' attachment status as assessed by the Adult Attachment Interview. AB - This study explored whether Japanese mothers' attachment status, as judged by the Adult Attachment Interview (AAI), would affect the way they perceive their child's amae. Amae, an indigenous Japanese concept of relatedness, has troubled, fascinated, and even mystified scholars across disciplines. In particular, amae has been sometimes misconstrued as the insecure-ambivalent pattern of attachment due to their apparent behavioral similarities. In an attempt to explore an empirical link between attachment and amae, Japanese mothers' (N = 47) views on their six-year-olds' amae were examined based on a brief amae questionnaire, given following the standard AAI. Mothers generally reported their child's amae similarly for questions of frequency (e.g., how often your child exhibits amae behaviors) or situations (e.g., in what circumstances your child most often engages in amae). However, a difference emerged when mothers' free descriptions of their child's amae were examined for the content quality, categorized, and analyzed against their secure/insecure attachment statuses. Secure mothers depicted their child's amae as being more affective, thus more welcoming, whereas insecure mothers depicted their child's typical amae as being more instrumental or manipulative, thus perhaps less welcoming. Japanese mothers' current states of mind with respect to attachment do appear to affect the way they perceive their child's typical amae. Future research on attachment and amae is discussed. PMID- 22044309 TI - Unemployment and mental health in a favorable labor market. AB - Labour market variables may moderate the link between unemployment and mental health, as has been found in numerous research papers. The aim of this study was to test, in the context of a very favorable labor market, (1) the detrimental effect of unemployment on mental health and (2) the predictive validity of mental health on further employment status. The population of the study comprised 384 newly registered unemployed persons. Mental health was assessed through four variables: self-esteem, psychological distress, perceived stress, and depressive symptoms. The results did not confirm previous studies. Using analyses of variance for repeated measures and linear regression, a negative change of mental health was not found after 6 and 12 months' unemployment, and the four measurements of mental health at registration did not predict employment status 6 and 12 months later. Results are discussed in terms of moderating variables that capture Luxembourg labor market specificities. This research was supported by the Luxembourg National Research Fund in the framework of the VIVRE Program; grant no. FNR/02/05/07. We would like to thank Mary Devine for the linguistic revision of the text. PMID- 22044310 TI - Premigration ethnic and national identities: Jewish adolescents planning emigration from Russia and Ukraine to Israel. AB - The ethnic and national identities of Jewish high-school adolescents planning emigration from Russia and Ukraine to Israel were investigated about six months before their emigration. The national identities of adolescent emigrants (n = 243) were compared with those of non-emigrant Russian and Ukrainian adolescents (n = 740). The emigrants' attitude to their country of origin was less positive and their identification with Russians and Ukrainians was weaker as compared with the non-emigrant adolescents. In addition, the attitude of the emigrants towards Israel was more positive than their attitude to Russia or Ukraine. Finally, the emigrants' strongest identification was with the Jewish people, followed by identification with Israelis, while their weakest identification was with Russians and Ukrainians. Israeli and Jewish identities of the emigrant adolescents were positively correlated, and they were independent of the Russian and Ukrainian identities. Perceived discrimination was negatively correlated with the emigrants' attitude to Russia or Ukraine, and it was positively correlated with the emigrants' identification with Israelis and with the Jewish people. Jewish ethnicity was correlated with identification with Jewish people; however, it was not correlated with any component of the Israeli or Russian/Ukrainian identities. The study results indicate that in the premigration period emigrants form a multidimensional system of ethnic and national identities, which reflects their partial detachment from their homeland and affiliation with the country of provisional immigration. This premigration identity system may be termed "anticipatory" (cf. Merton, 1968), because it is not based on real contact with the country of provisional immigration, but rather on the emigrants' expectations. On the other hand, the premigration identities are reactive, in the sense that they reflect the emigrants' reaction to the perceived discrimination they experience in their country of origin. The results of the present study are discussed in light of social identity theory. PMID- 22044311 TI - The catalytic asymmetric Fischer indolization. AB - The first catalytic asymmetric Fischer indolization is reported. In the presence of a 5 mol % loading of a novel spirocyclic chiral phosphoric acid, 4-substituted cyclohexanone-derived phenylhydrazones undergo a highly enantioselective indolization. Efficient catalyst turnover was achieved by the addition of a weakly acidic cation exchange resin, which removes the generated ammonia. The reaction can be conducted under mild conditions and gives various 3-substituted tetrahydrocarbazoles in generally high yields. PMID- 22044312 TI - Expression of natural killer cell activating receptors in patients with chronic lymphocytic leukaemia. AB - Recent advances in chronic lymphocytic leukaemia (CLL) treatment, more particularly through upfront use of anti-CD20 monoclonal antibodies, have prolonged patient progression-free survival. Nonetheless, apart from allogeneic stem cell transplantation, no curative treatment is available. One possible explanation for the lack of cure in CLL could be a defective immune anti-tumour response. As the result of abnormal HLA class I molecule expression, CLL cells escape from specific T-lymphocyte immunity but should be the target for the innate natural killer (NK) cell-mediated immune response. Defective NK cytotoxicity as the result of decreased expression of the natural cytotoxicity receptors (NCRs) NKp30/NCR3, NKp44/NCR2 and NKp46/NCR1 has been described in haematological malignancies such as acute myeloid leukaemia. This prompted us to focus our attention on NCR expression on NK cells from patients with CLL. Although we failed to detect any difference between CLL patients and healthy age matched controls, a precise analysis of clinical data showed a correlation between decreased NCR expression and poor prognosis factors such as low haemoglobin level, high (>30*10(9) per litre) lymphocyte count or elevated C reactive protein. Together, these observations support the rationale for restoration of normal NK cell functions in patients with CLL, putatively through the use of immune therapy protocols that already have demonstrated some benefit in acute myeloid leukaemia such as interleukin-2 plus histamine dihydrochloride. PMID- 22044313 TI - Interleukin-6 mediates pulmonary vascular permeability in a two-hit model of ventilator-associated lung injury. AB - To test the hypothesis that interleukin-6 (IL-6) contributes to the development of ventilator-associated lung injury (VALI), IL-6-deficient (IL6(-/-)) and wild type control (WT) mice received intratracheal hydrochloric acid followed by randomization to mechanical ventilation (MV + IT HCl) or spontaneous ventilation (IT HCl). After 4 hours, injury was assessed by estimation of lung lavage protein concentration and total and differential cell counts, wet/dry lung weight ratio, pulmonary cell death, histologic inflammation score (LIS), and parenchymal myeloperoxidase (MPO) concentration. Vascular endothelial growth factor (VEGF) concentration was measured in lung lavage and homogenate, as IL-6 and stretch both regulate expression of this potent mediator of permeability. MV-induced increases in alveolar barrier dysfunction and lavage VEGF were attenuated in IL6( /-) mice as compared with WT controls, whereas tissue VEGF concentration increased. The effects of IL-6 deletion on alveolar permeability and VEGF concentration were inflammation independent, as parenchymal MPO concentration, LIS, and lavage total and differential cell counts did not differ between WT and IL6(-/-) mice following MV + IT HCl. These data support a role for IL-6 in promoting VALI in this two-hit model. Strategies to interfere with IL-6 expression or signaling may represent important therapeutic targets to limit the injurious effects of MV in inflamed lungs. PMID- 22044314 TI - Hydration and temperature dependence of 13C and 1H NMR spectra of the DMPC phospholipid membrane and complete resonance assignment of its crystalline state. AB - Inhomogeneous line broadening due to conformational distributions of molecules is one of the troublesome problems in solid-state NMR spectroscopy. The best possible way to avoid it is to crystallize the sample. Here, we present a highly resolved (13)C cross-polarization (CP) magic angle spinning (MAS) NMR spectrum of the highly ordered crystalline 1,2-dimyrystoyl-sn-glycero-3-phosphocholine (DMPC) and completely assigned it using two-dimensional (2D) solid-state NMR spectra, dipolar heteronuclear correlation (HETCOR) spectra, scalar heteronuclear J coupling based chemical shift correlation (MAS-J-HMQC) spectra, and Dipolar Assisted Rotational Resonance (DARR) spectra. A comparison between assigned chemical shift values by solid-state NMR in this study and the calculated chemical shift values for X-ray crystal DMPC structures shows good agreement, indicating that the two isomers in the crystalline DMPC take the same conformation as the X-ray crystal structure. The phase diagram of the low hydration level of DMPC (3 <= n(W) <= 12) determined by (1)H and (13)C NMR spectra indicates that DMPC takes a crystalline state only in a very narrow region around n(W) = 4 and T < 313 K. These findings provide us with conformational information on crystalline DMPC and the physical properties of DMPC at a low hydration level and can possibly help us obtain a highly resolved solid-state NMR spectrum of microcrystalline membrane-associated protein samples. PMID- 22044315 TI - Modeling inhalational tularemia: deliberate release and public health response. AB - Two epidemic modeling studies of inhalational tularemia were identified in the published literature, both demonstrating the high number of potential casualties that could result from a deliberate aerosolized release of the causative agent in an urban setting. However, neither study analyzed the natural history of inhalational tularemia nor modeled the relative merits of different mitigation strategies. We first analyzed publicly available human/primate experimental data and reports of naturally acquired inhalational tularemia cases to better understand the epidemiology of the disease. We then simulated an aerosolized release of the causative agent, using airborne dispersion modeling to demonstrate the potential number of casualties and the extent of their spatial distribution. Finally, we developed a public health intervention model that compares 2 mitigation strategies: targeting antibiotics at symptomatic individuals with or without mass distribution of antibiotics to potentially infected individuals. An antibiotic stockpile that is sufficient to capture all areas where symptomatic individuals were infected is likely to save more lives than treating symptomatic individuals alone, providing antibiotics can be distributed rapidly and their uptake is high. However, with smaller stockpiles, a strategy of treating symptomatic individuals alone is likely to save many more lives than additional mass distribution of antibiotics to potentially infected individuals. The spatial distribution of symptomatic individuals is unlikely to coincide exactly with the path of the dispersion cloud if such individuals are infected near their work locations but then seek treatment close to their homes. The optimal mitigation strategy will depend critically on the size of the release relative to the stockpile level and the effectiveness of treatment relative to the speed at which antibiotics can be distributed. PMID- 22044317 TI - Cancerous cell death from sensitizer free photoactivation of singlet oxygen. AB - Singlet oxygen ((1)O(2)) is an electronic state of molecular oxygen which plays a major role in many chemical and biological photo-oxidation processes. It has a high chemical reactivity which is commonly harnessed for therapeutic issues. Indeed, (1)O(2) is believed to be the major cytotoxic agent in photodynamic therapy. In this treatment of cancer, (1)O(2) is created, among other reactive species, by an indirect transfer of energy from light to molecular oxygen via excitation of a photosensitizer (PS). This PS is believed to be necessary to obtain an efficient (1)O(2) production. In this paper, we demonstrate that production of (1)O(2) is achieved in living cells from PS-free 1270 nm laser excitation of molecular oxygen. The quantity of (1)O(2) produced in this way is sufficient to induce an oxidative stress leading to cell death. Other effects such as thermal stress are discriminated and we conclude that cell death is only due to (1)O(2) creation. This new simplified scheme of (1)O(2) activation can be seen as a breakthrough for phototherapies of malignant diseases and/or as a noninvasive possibility to generate reactive oxygen species in a tightly controlled manner. PMID- 22044316 TI - BAY 41-2272, a soluble guanylate cyclase agonist, activates human mononuclear phagocytes. AB - BACKGROUND AND PURPOSE: Phagocyte function is critical for host defense against infections. Defects in phagocytic function lead to several primary immunodeficiencies characterized by early onset of recurrent and severe infections. In this work, we further investigated the effects of BAY 41-2272, a soluble guanylate cyclase (sGC) agonist, on the activation of human peripheral blood monocytes (PBM) and THP-1 cells. EXPERIMENTAL APPROACH: THP-1 cells and PBM viability was evaluated by methylthiazoletetrazolium assay; reactive oxygen species production by lucigenin chemiluminescence; gene and protein expression of NAPDH oxidase components by qRT-PCR and Western blot analysis, respectively; phagocytosis and microbicidal activity by co-incubation, respectively, with zymosan and Escherichia coli; and cytokine release by elisa. KEY RESULTS: BAY 41 2272, compared with the untreated group, increased spreading of monocytes by at least 35%, superoxide production by at least 50%, and gp91(PHOX) and p67(PHOX) gene expression 20 to 40 times, in both PBM and THP-1 cells. BAY 41-2272 also augmented phagocytosis of zymosan particles threefold compared with control, doubled microbicidal activity against E. coli and enhanced the release of TNF alpha and IL-12p70 by both PBM and THP-1 cells. Finally, by inhibiting sGC with ODQ, we showed that BAY 41-2272-induced superoxide production and phagocytosis is not dependent exclusively on sGC activation. CONCLUSIONS AND IMPLICATIONS: In addition to its ability to induce vasorelaxation and its potential application for therapy of vascular diseases, BAY 41-2272 was shown to activate human mononuclear phagocytes. Hence, it is a novel pro-inflammatory drug that may be useful for controlling infections in the immunocompromised host. PMID- 22044318 TI - Femtosecond transient absorption, nanosecond time-resolved resonance Raman, and density functional theory study of fenofibric acid in acetonitrile and isopropyl alcohol solvents. AB - Hydrogen abstraction reaction of fenofibric acid (FA) in acetonitrile and isopropyl alcohol solvents was studied by femtosecond transient absorption (fs TA) and nanosecond time-resolved resonance Raman (ns-TR(3)) spectroscopy experiments. The singlet excite state ((1)FA) (npi*) with a maximum transient absorption at 352 nm observed in the fs-TA experiments undergoes efficient intersystem crossing (ISC) to convert into a npi* triplet state FA ((3)FA) that exhibits two transient absorption bands at 345 and 542 nm. The npi* (3)FA species does not decay obviously within 3000 ps. In the ns-TR(3) experiments, the npi* (3)FA is also observed and completely decays by 120 ns. Compared with the triplet states of benzophenone (BP) and ketoprofen (KP), the npi* (3)FA species seems to have a much higher hydrogen abstraction reactivity so that (3)FA decays fast and generates a FA ketyl radical like species. In isopropyl alcohol solvent, the npi* (3)FA exhibits similar reactivity and promptly abstracts a hydrogen from the strong hydrogen donor isopropyl alcohol solvent to generate a ketyl radical intermediate. With the decay of the FA ketyl radical, no light absorption transient (LAT) intermediate is observed in isopropyl alcohol solvent although such a LAT species was observed after similar experiments for BP and KP. Comparison of the ns-TR(3) spectra for the species of interest with results from density functional theory calculations were used to elucidate the identity, structure, properties, and major spectral features of the intermediates observed in the ns-TR(3) spectra. This comparison provides insight into the structure and hydrogen abstraction reactivity of the triplet states of BP derivatives. PMID- 22044319 TI - Risk and markets for ecosystem services. AB - Market-based environmental regulations (e.g., cap and trade, "payments for ecosystem services") are increasingly common. However, few detailed studies of operating ecosystem markets have lent understanding to how such policies affect incentive structures for improving environmental quality. The largest U.S. market stems from the Clean Water Act provisions requiring ecosystem restoration to offset aquatic ecosystems damaged during development. We describe and test how variations in the rules governing this ecosystem market shift risk between regulators and entrepreneurs to promote ecological restoration. We analyze extensive national scale data to assess how two critical aspects of market structure - (a) the geographic scale of markets and (b) policies dictating the release of credits - affect the willingness of entrepreneurs to enter specific markets and produce credits. We find no discernible relationship between policies attempting to ease market entry and either the number of individual producers or total credits produced. Rather, market entry is primarily related to regional geography (the prevalence of aquatic ecosystems) and regional economic growth. Any improvements to policies governing ecosystem markets require explicit evaluation of the interplay between policy and risk elements affecting both regulators and entrepreneurial credit providers. Our findings extend to emerging, regulated ecosystem markets, including proposed carbon offset mechanisms, biodiversity banking, and water quality trading programs. PMID- 22044321 TI - Judge allows bulk ingredients for compounding: ruling favors pharmacy, but FDA can still distinguish manufacturing, compounding. PMID- 22044322 TI - Unconventional nutritional therapy versus conventional veterinary nutrition. PMID- 22044323 TI - What is your diagnosis? Retained surgical sponge. PMID- 22044324 TI - Theriogenology question of the month. Hypospadias. PMID- 22044325 TI - Animal behavior case of the month. Hyperactivity. PMID- 22044326 TI - Pathology in practice. Mycotic dermatitis, cellulitis, and myositis. PMID- 22044327 TI - Executive summary of phase 2 of the Bayer veterinary care usage study. PMID- 22044328 TI - Epidemiology of struvite uroliths in ferrets: 272 cases (1981-2007). AB - OBJECTIVE: To confirm that the predominant mineral type in naturally occurring uroliths in ferrets is struvite; to determine whether age, breed, sex, reproductive status, geographic location, season, and anatomic location are risk factors associated with urolith formation in ferrets; to compare features of struvite uroliths in cats with those in ferrets; and to determine whether there is a logical evidence-based rationale for clinical trials of the safety and efficacy of diet-induced dissolution of struvite uroliths in ferrets. DESIGN: Retrospective case-control study. ANIMALS: 408 ferrets with uroliths (272 struvite uroliths) from the Minnesota Urolith Center, and 6,528 control ferrets from the Veterinary Medical Database. PROCEDURES: Historical information was obtained about each ferret. The association between proposed risk factors and outcome (struvite urolith formation) was assessed. RESULTS: Sterile struvite was the predominant mineral in uroliths in ferrets. Neutered male ferrets had a significantly increased risk of developing sterile struvite uroliths. A significant association was also found between increasing age and the detection of struvite uroliths. Struvite uroliths in ferrets were more likely to be retrieved from the lower urinary tract than from the upper urinary tract. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of predominant mineral type in uroliths along with insight into etiologic, demographic, and environmental risk and protective factors for urolithiasis may facilitate development of surveillance strategies that result in earlier detection of uroliths in ferrets. Modification of risk factors, including dietary risk factors, may help to minimize urolith formation, dissolve existing uroliths, and minimize urolith recurrence. PMID- 22044329 TI - Mass-to-splenic volume ratio and splenic weight as a percentage of body weight in dogs with malignant and benign splenic masses: 65 cases (2007-2008). AB - OBJECTIVE: To determine whether mass-to-splenic volume ratio or splenic weight as a percentage of body weight was significantly different between dogs with benign versus malignant splenic masses. DESIGN: Retrospective case series. ANIMALS: 65 dogs that underwent splenectomy. PROCEDURES: Medical records of dogs examined between October 2007 and June 2008 because of a splenic mass were reviewed. Information obtained included dog age, breed, and weight; whether hemoperitoneum was present; splenic weight and dimensions (length, width, and height) at the time of splenectomy; dimensions (length, width, and height) of the splenic mass; and histologic diagnosis. Information on survival time was recorded when available. RESULTS: 30 (46%) dogs had hemangiosarcoma, 10 (15%) had other types of malignant masses, and 25 (39%) had benign masses. Dogs with benign splenic masses had a significantly higher mean mass-to-splenic volume ratio and higher mean splenic weight as a percentage of body weight than did dogs with hemangiosarcoma. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that mass to-splenic volume ratio and splenic weight as a percentage of body weight may be useful in differentiating between hemangiosarcoma and benign lesions in dogs with splenic masses. PMID- 22044330 TI - Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie. AB - CASE DESCRIPTION: A 2-year-old spayed female Border Collie was treated with IV lipid emulsion (ILE) after ingesting 6 mg/kg (2.73 mg/lb) of an equine ivermectin anthelmintic paste 8 hours prior to examination. CLINICAL FINDINGS: On initial examination, the dog had stable cardiovascular signs but had diffuse muscle tremors and was hyperthermic. Neurologic evaluation revealed that the dog was ataxic and had mydriasis with bilaterally absent menace responses and pupillary light reflexes. The remaining physical examination findings were unremarkable. Results of CBC, serum biochemical analysis, venous blood gas analysis, and measurement of plasma lactate concentration were also within reference limits. TREATMENT AND OUTCOME: The dog was treated with ILE in addition to supportive care with IV fluid therapy and cardiovascular, respiratory, and neurologic monitoring. The use of ILE treatment was initiated in this patient on the basis of previous clinical and experimental evidence supporting its use for toxicosis resulting from lipid-soluble agents. An initial bolus of 1.5 mL/kg (0.68 mL/lb) of a 20% sterile lipid solution was administered IV over 10 minutes, followed by a constant rate infusion of 0.25 mL/kg/min (0.11 mL/lb/min) over 60 minutes that was administered twice to treat clinical signs of ivermectin toxicosis. The dog was discharged from the hospital 48 hours after admission and was clinically normal within 4 days after ivermectin ingestion. Further diagnostic evaluation subsequently revealed that this dog was unaffected by the multidrug resistance gene (MDR-1) deletion, known as the ATP-binding cassette polymorphism. CLINICAL RELEVANCE: Ivermectin toxicosis in veterinary patients can result in death without aggressive treatment, and severe toxicosis often requires mechanical ventilation and intensive supportive care. This is particularly true in dogs affected by the ATP-binding cassette polymorphism. Novel ILE treatment has been shown to be effective in human patients with lipid-soluble drug toxicoses, although the exact mechanism is unknown. In the patient in the present report, ILE was used successfully to treat ivermectin toxicosis, and results of serial measurement of serum ivermectin concentration supported the proposed lipid sink mechanism of action. PMID- 22044331 TI - Assessment of the tissue diffusion of anesthetic agent following administration of a low palmar nerve block in horses. AB - OBJECTIVE: To investigate tissue diffusion of anesthetic agent following administration of low palmar nerve blocks (LPBs) in horses. DESIGN: Randomized clinical trial. ANIMALS: 12 adult horses. PROCEDURES: In 9 horses, mepivacaine hydrochloride-iohexol (50:50 dilution) injections were administered bilaterally (2 or 4 mL/site) to affect the medial and lateral palmar and palmar metacarpal nerves (4 sites). Lateral radiographic views of both metacarpal regions were obtained before and at 5, 15, 30, 60, 90, and 120 minutes after block administration; proximal and distal extents of contrast medium (and presumably anesthetic agent) diffusion from palmar and palmar metacarpal injection sites were measured and summed to determine total diffusion. Methylene blue solution was injected in forelimbs of 3 other horses that were subsequently euthanized to determine the potential route of anesthetic agent diffusion to the proximal suspensory ligament region. RESULTS: Mean extents of proximal and total contrast medium diffusion were 4.0 and 6.6 cm, respectively, for the palmar metacarpal nerves and 4.3 and 7.1 cm, respectively, for the palmar nerves. Subtle proximal diffusion secondary to lymphatic drainage was evident in 17 of the 18 limbs. Contrast medium was detected in the metacarpophalangeal joint or within the digital flexor tendon sheath in 8 and 7 limbs, respectively. In the cadaver limbs, methylene blue solution did not extend to the proximal suspensory ligament region. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, LPBs resulted in minimal proximal diffusion of anesthetic agent from the injection sites. Limbs should be aseptically prepared prior to LPB administration because inadvertent intrasynovial injection may occur. PMID- 22044332 TI - Agreement between arterial partial pressure of carbon dioxide and saturation of hemoglobin with oxygen values obtained by direct arterial blood measurements versus noninvasive methods in conscious healthy and ill foals. AB - OBJECTIVE: To determine agreement between indirect measurements of end-tidal partial pressure of carbon dioxide (PetCO(2)) and saturation of hemoglobin with oxygen as measured by pulse oximetry (SpO(2)) with direct measurements of PaCO(2) and calculated saturation of hemoglobin with oxygen in arterial blood (SaO(2)) in conscious healthy and ill foals. DESIGN: Validation study. ANIMALS: 10 healthy and 21 ill neonatal foals. PROCEDURES: Arterial blood gas analysis was performed on healthy and ill foals examined at a veterinary teaching hospital to determine direct measurements of PaCO(2) and PaO(2) along with SaO(2). Concurrently, PetCO(2) was measured with a capnograph inserted into a naris, and SpO(2) was measured with a reflectance probe placed at the base of the tail. Paired values were compared by use of Pearson correlation coefficients, and level of agreement was assessed with the Bland-Altman method. RESULTS: Mean +/- SD difference between PaCO(2) and PetCO(2) was 0.1 +/- 5.0 mm Hg. There was significant strong correlation (r = 0.779) and good agreement between PaCO(2) and PetCO(2). Mean +/- SD difference between SaO(2) and SpO(2) was 2.5 +/- 3.5%. There was significant moderate correlation (r = 0.499) and acceptable agreement between SaO(2) and SpO(2). CONCLUSIONS AND CLINICAL RELEVANCE: Both PetCO(2) obtained by use of nasal capnography and SpO(2) obtained with a reflectance probe are clinically applicable and accurate indirect methods of estimating and monitoring PaCO(2) and SaO(2) in neonatal foals. Indirect methods should not replace periodic direct measurement of corresponding parameters. PMID- 22044333 TI - Reflux of drug during intra-vitreal anti-VEGF therapies. AB - PURPOSE: To report reflux of anti-VEGF drug during intravitreal injections. METHOD: Review of electronic case notes of patients undergoing intra-vitreal anti VEGF treatments. Prospective data collection was performed with a specific emphasis on presence or absence of reflux. RESULTS: 152 records of 102 eyes were available from an 8-month period. 119 Ranibizumab injections and 33 bevazicumab injections were considered. Reflux was noted in 48 injections (31%). For eyes with first injection of anti-VEGF agent, reflux was noted in 9/23 eyes. Eyes with at least one previous injection were observed to have reflux in 24/79 eyes. Presence of reflux was statistically tested against posterior vitreous detachment and phakic status and was found to be statistically insignificant. CONCLUSION: Intra-vitreal anti-VEGF injections with volumes of 0.05 ml appears to produce displacement of the conjunctiva with a transient fluid-filled bleb immediately after the injection in approximately 1/3 of eyes. PMID- 22044334 TI - Treatment for submacular hemorrhage associated with neovascular age-related macular degeneration. AB - Submacular hemorrhage associated with neovascular age-related macular degeneration is a complication known to have potentially devastating effects on visual acuity. Multiple treatment modalities have been suggested including intravitreal anti-vascular endothelial growth factor injections, photodynamic therapy, pneumatic displacement with or without adjuvant intravitreal tissue plasminogen activator, and pars plana vitrectomy with or without adjuvant subretinal tissue plasminogen activator. However, there remains no consensus on optimal treatment, as clinical trials for neovascular age-related macular degeneration have excluded patients with submacular hemorrhage. This manuscript offers guidelines to the management of subretinal hemorrhage based on its size and characteristics, and highlights the need for clinical trials in this area. PMID- 22044335 TI - Review of ranibizumab trials for neovascular age-related macular degeneration. AB - Ranibizumab, a recombinant, humanized, monoclonal antibody antigen-binding fragment that neutralizes all VEGF-A isoforms, is the first US FDA-approved therapy for neovascular age-related macular degeneration (AMD) to result in improvement in visual acuity. The benefit of intravitreal ranibizumab applies to all angiographic subtypes of neovascular AMD and across all lesion sizes. The two original phase III studies (ANCHOR and MARINA) demonstrated sustained visual acuity (VA) gains over a two-year monthly dosing schedule. Following these trials, several studies looked at ways to decrease the treatment burden while maintaining similar visual gains. These trials included PIER, PrONTO, EXCITE, SUSTAIN, HORIZON, and CATT. Visual acuity data shows that monthly dosing of ranibizumab produces superior vision outcomes compared to a less-frequent, fixed dosing schedule. Intravitreal ranibizumab is well tolerated and shown to have a very low rate of adverse ocular or systemic side-effects. PMID- 22044336 TI - Administration of repeat intravitreal anti-VEGF drugs by retina specialists in an injection-only clinic for patients with exudative AMD: patient acceptance and safety. AB - PURPOSE: To report patient acceptance and safety of repeated intravitreal injections of anti-VEGF agents for exudative AMD, by retina specialists, without an eye examination before every injection. METHODS: Retrospective chart review. 115 eyes (110 patients) with exudative AMD underwent repeated intravitreal anti VEGF injections with limited interval examination and diagnostic testing. Medication, laterality, number of injection cycles started and completed, number of injections per injection cycle, subjective visual changes, pre- and post injection visual acuity (VA), pre- and post-injection intraocular pressure (IOP), nurse- and patient-initiated phone calls, emergency (non-scheduled) clinic visits, complications, new diagnoses, and patient complaints after each injection were recorded. The main outcome measures were complications and patient complaints. RESULTS: 396 injections were administered in the injection clinic to 110 patients in 175 injection cycles (range: 0 to 5 injections per cycle). Of 175 injection cycles, there were 134 uninterrupted cycles and 41 interrupted cycles where an eye exam was performed. Fourteen new diagnoses were made: six during emergency visits, three at injection clinic appointments, and five at the next full examination after completion of a prescribed injection clinic cycle. CONCLUSIONS: Administration of anti-VEGF injections in a designated injection clinic, by retina specialists, according to a prescribed schedule, and with limited pre-injection testing, for patients with wet AMD, is well-tolerated. PMID- 22044337 TI - Rapid resolution of macular edema associated with central retinal vein occlusion using ranibizumab after failure with multiple bevacizumab injections. AB - PURPOSE: To report improvement in cystoid macular edema from central retinal vein occlusion with one injection of ranibizumab after failure with seven injections of bevacizumab. METHODS: Case report. RESULTS: A 74-year-old female developed persistent blurred vision for three months. Ocular examination revealed macular edema secondary to nonischemic central retinal vein occlusion. The patient was treated with intravitreal bevacizumab (1.25 mg in 0.05 mL). She received seven injections (every 5-6 weeks). Vision fluctuated between 20/30 and 20/60 with minimal variation in central foveal thickness (449-574 MUm). However, weeks after one injection of ranibizumab the patient's vision improved to 20/20 with near resolution of macular edema (CFT = 343 MUm). CONCLUSIONS: Patients with no response to bevacizumab injections can show a rapid and large improvement with ranibizumab. This underscores the important differences between these two medications. Further study is required to determine if these initial effects of ranibizumab can be maintained. PMID- 22044338 TI - Salt-stress induced physiological and proteomic changes in tomato (Solanum lycopersicum) seedlings. AB - Soil salinity is one of the major abiotic stress limiting crop productivity and the geographical distribution of many important crops worldwide. To gain a better understanding of the salinity stress responses at physiological and molecular level in cultivated tomato (Solanum lycopersicum. cv. Supermarmande), we carried out a comparative physiological and proteomic analysis. The tomato seedlings were cultivated using a hydroponic system in the controlled environment growth chamber. The salt stress (NaCl) was applied (0, 50, 100, 150 and 200 mM), and maintained for 14 days. Salt treatment induced a plant growth reduction estimated as fresh-dry weight. Photosynthetic pigments (chlorophyll a, b) content of NaCl treated tomato plants was significantly decreased as the salinity level increased. Proline accumulation levels in leaf and root tissues increased significantly with increasing NaCl concentration. Relative electrolyte leakage known as an indicator of membrane damage caused by salt stress was increased proportionally according to the NaCl concentrations. Roots of control and salt stressed plants were also sampled for phenol protein extraction. Proteins were separated by two-dimensional gel electrophoresis (2-DGE). Several proteins showed up- and downregulation during salt stress. MALDI-TOF/MS analysis and database searching of some of the identified proteins indicated that the proteins are known to be in a wide range of physiological processes, that is, energy metabolism, ROS (reactive oxygen species) scavenging and detoxification, protein translation, processing and degradation, signal transduction, hormone and amino acid metabolism, and cell wall modifications. All proteins might work cooperatively to reestablish cellular homeostasis under salt stress, water deficiency, and ionic toxicity. PMID- 22044340 TI - Complaint of insomnia as a predictor of aging symptoms in males at a men's health clinic. AB - INTRODUCTION: Issues of men's health have been greatly researched by scholars in recent decades. At men's health clinics, many patients complain of both insomnia and aging males' symptoms (AMS). These symptoms might be influenced by biological, psychological or even social factors. The aim of this study was to investigate different aspects of the relationship between insomnia and aging symptoms. METHODS: This cross-sectional study included 231 males from a men's health clinic. Participants completed a set of general data and screening assessments, including the AMS rating scale, insomnia severity index (ISI), Beck depression inventory-II (BDI-II) and Beck anxiety inventory Chinese version (BAI), to investigate the severity of aging symptoms, insomnia, depression and anxiety. RESULTS: The ISI correlated significantly with the AMS scale, both with (partial correlation coefficient = 0.470) and without (r = 0.580) controlled variances of depression and anxiety. Using linear regression, aging symptoms were statistically predicted by the severity of the ISI, and a substantial proportion of the variance was explained (adjusted R(2) = 0.410). When all variables were included, this proportion rose to 55.3% (adjusted R(2) = 0.553). CONCLUSION: We suggest that insomnia is a good predictor of aging symptoms across all age groups of men. PMID- 22044339 TI - Cytomegalovirus-specific CD8+ T cells targeting different peptide/HLA combinations demonstrate varying T-cell receptor diversity. AB - Cytomegalovirus (CMV) infection and reactivation pose a serious threat for patients after haematopoietic stem cell transplantation. We have previously shown that CD8(+) T cells targeting different CMV epitopes correlate with protection at different threshold frequencies in those patients. To investigate if this may relate to a different quality of these cells here we analyse the T-cell receptor diversity of pp50 (245-253)/HLA-A*0101 specific CD8(+) T cells with that of CD8(+) T cells targeting various pp65 peptides. The results from this pilot study show differences in the breadth of the T-cell receptor usage of the different cell populations. We observe for the first time that the T-cell receptor Vbeta CDR3 spectratypes used by CMV pp50 (245-253)/HLA-A*0101-specific CD8(+) T cells can reach higher numbers than those used by CD8(+) T cells targeting various pp65 peptides in our patient cohort. This merits further investigation into the effectiveness of the different CMV-specific T cells and their impact on immunosenescence, which is important to eventually define the most useful source of adoptive therapy and monitoring protocols for cytomegalovirus-specific immune responses. PMID- 22044342 TI - Transient, transverse melanonychia associated with Graves disease and acute hepatitis. AB - Melanonychia is a black, tan, or brown streak within the nail plate subsequent to activation of melanocytes in the nail matrix. We present a case of a Haitian girl who presented with transverse melanonychia involving all 10 fingernails in the setting of hyperthyroidism and acute liver injury. Melanonychia has been described only one time in the literature in the setting of hyperthyroidism though this patient also underwent radium treatment which could have led to nail changes. PMID- 22044343 TI - Rapid selection of glucose-utilizing variants of the polyhydroxyalkanoate producer Ralstonia eutropha H16 by incubation with high substrate levels. AB - AIMS: The application of Ralstonia eutropha H16 for producing polyhydroxyalkanoates as bioplastics is limited by the incapability of the bacterium to utilize glucose as a growth substrate. This study aims in characterizing glucose-utilizing strains that arose after incubation with high glucose levels, in comparison with previously published mutants, generated either by mutagenesis or by metabolic engineering. METHODS AND RESULTS: Cultivations on solid and liquid media showed that the application of high substrate concentrations rapidly induced a glucose-positive phenotype. The time span until the onset of growth and the frequency of glucose-utilizing colonies were correlated to the initial glucose concentration. All mutants exhibited elevated activities of glucose-6-phosphate dehydrogenase. The glucose-positive phenotype was abolished after deleting genes for the N-acetylglucosamine phosphotransferase system. CONCLUSIONS: A procedure is provided for selecting glucose-utilizing R. eutropha H16 in an unprecedented short time period and without any mutagenic treatment. An altered N-acetylglucosamine phosphotransferase system appears to be a common motif in all glucose-utilizing mutants examined so far. SIGNIFICANCE AND IMPACT OF THE STUDY: The correlation of the applied glucose concentration and the appearance of glucose-utilizing mutants poses questions about the randomness or the specificity of adaptive mutations in general. Furthermore, glucose-adapted strains of R. eutropha H16 could be useful for the production of bioplastics. PMID- 22044344 TI - Identifying the mechanisms of polymer friction through molecular dynamics simulation. AB - Mechanisms governing the tribological behavior of polymer-on-polymer sliding were investigated by molecular dynamics simulations. Three main mechanisms governing frictional behavior were identified. Interfacial "brushing" of molecular chain ends over one another was observed as the key contribution to frictional forces. With an increase of the sliding speed, fluctuations in frictional forces reduced in both magnitude and periodicity, leading to dynamic frictional behavior. While "brushing" remained prevalent, two additional irreversible mechanisms, "combing" and "chain scission", of molecular chains were observed when the interfaces were significantly diffused. PMID- 22044345 TI - High total acrosin activity in varicocele individuals. AB - Varicocele is a common cause of male infertility and reports indicate that varicocelectomy has a beneficial effect on male fertility. The aims of this study were to evaluate and compare the total acrosin activity along with DNA integrity in semen samples obtained from 70 varicocele individuals with male factors infertility presenting grades II and III varicocele before and after the surgery and 30 fertile individuals without any clinical presentation of varicocele. Total acrosin activity, protamine deficiency, DNA fragmentation, and semen parameters including sperm concentration, motility and sperm morphology were assessed by spectrophotometery, CMA3 staining, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and WHO criteria, respectively. Total acrosin activity (P = 0.03), percentage CMA3 positivity (P = 0.00) and TUNEL-positive spermatozoa (P = 0.04) were higher in the varicocele individuals before the surgery compared with the fertile individuals; yet, all the aforementioned criteria decreased significantly after surgery (P < 0.05). The results of this study reveal that DNA fragmentation and protamine deficiency, as negative parameters in fertility, improve post-surgery; however, total acrosin activity as a positive parameter in fertility is higher in the varicocele individuals compared with fertile and decreases to a value close to the fertile control post surgery. High levels of total acrosin activity in varicocele individuals need more research in future. PMID- 22044346 TI - Quercetin suppresses cytochrome P450 mediated ROS generation and NFkappaB activation to inhibit the development of 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinomas. AB - Increased production of reactive oxygen species (ROS) has long been recognized to play a pivotal role in carcinogenesis. Quercetin, a naturally occurring dietary flavonoid is known for its ROS scavenging properties. The present study was designed to investigate the chemopreventive and chemotherapeutic effects of quercetin based on cytochrome P450 (CYP) mediated ROS generation, ROS-induced cellular damage and activation of the NFkappaB signalling circuit during 7,12 dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Administration of quercetin inhibited the development of DMBA induced HBP carcinomas by impairing CYP-mediated ROS production via downregulation of the expression of CYP1A1 and CYP1B1, and upregulation of antioxidant defences. Attenuation of ROS generation by quercetin in turn abrogated NFkappaB signalling by preventing the phosphorylation and degradation of IkappaB, nuclear translocation of NFkappaB and transactivation of its target genes associated with cell proliferation and apoptosis evasion. Thus dietary flavonoids such as quercetin that can block ROS generation and inhibit the redox regulated transcription factor NFkappaB, by virtue of their antioxidant potential are promising candidates for future antioxidant-based anticancer regimens. PMID- 22044347 TI - Mapping nanomagnetic fields using a radical pair reaction. AB - We used a fluorescent chemical indicator of magnetic field to visualize the magnetic field around ferromagnetic nanostructures. The indicator was a chain linked electron donor-acceptor molecule, phenanthrene-(CH2)12-O-(CH2)2 dimethylaniline, that forms spin-correlated radical pairs upon photoexcitation. The magnetic field altered the coherent spin dynamics, yielding an 80% increase in exciplex fluorescence in a 0.1 T magnetic field. The magnetic field distributions were quantified to precision of 1.8*10(-4) T by image analysis and agreed with finite-element nanomagnetic simulations. PMID- 22044348 TI - New perspectives of gibberellic acid production: a review. AB - The gibberellins (GAs) are an important group of hormones which exert various effects on promoter and regulator of plant growth. Gibberellic acid (GA(3)) is a natural plant hormone, with great economical and industrial importance. It affects stem elongation, germination, elimination of dormancy, flowering, sex expression, enzyme induction and leaf and fruit senescence. Despite its diverse applications, the use of GA(3) is limited due to its high production costs. The industrial process currently used for the production of GA(3) is based on submerged fermentation (SmF) techniques. As an alternative for its production, solid state fermentation (SSF) has also been investigated for its ability to increase the yields of GA(3) with the use of agro-industrial wastes as support/substrate, which contributes to the decreased production costs. This review describes GA(3)'s physical, chemical and biological properties, its production by fermentation and new advances that are being carried out with special interest on the SSF technique. PMID- 22044349 TI - Localized surface plasmon resonances of anisotropic semiconductor nanocrystals. AB - We demonstrate that anisotropic semiconductor nanocrystals display localized surface plasmon resonances that are dependent on the nanocrystal shape and cover a broad spectral region in the near-IR wavelengths. In-plane and out-of-plane dipolar resonances were observed for colloidal dispersions of Cu(2-x)S nanodisks, and the wavelengths of these resonances are in good agreement with calculations carried out in the electrostatic limit. The wavelength, line shape, and relative intensities of these plasmon bands can be tuned during the synthetic process by controlling the geometric aspect ratio of the disk or using a postsynthetic thermal-processing step to increase the free carrier densities. PMID- 22044350 TI - Recent trends in Veterans Affairs chronic condition spending. AB - The change in prevalence and total Veterans Affairs (VA) spending were estimated for 16 chronic condition categories between 2000 and 2008. The drivers of changes in spending also were examined. Chronic conditions were identified through diagnoses in encounter records, and treatment costs per patient were estimated using VA cost data and regression models. The estimated differences in total VA spending between 2000 and 2008 and the contributions of population increase, differences in prevalence, and differences in treatment costs were evaluated. Most of the spending increases during the study period were driven by the increase in the VA patient population from 3.3 million in 2000 to 4.9 million in 2008. Spending on renal failure increased the most, by more than $1.5 billion, primarily because of higher prevalence. Higher treatment costs did not contribute much to higher spending; lower costs per patient for several conditions may have helped to slow spending for diabetes, chronic obstructive pulmonary disease, heart conditions, renal failure, dementia, and stroke. Lowering treatment costs per patient for common conditions can help slow spending for chronic conditions, but most of the increase in spending in the study period was the result of more patients seeking care from VA providers and the higher prevalence of conditions among patients. As the VA patient population continues to age and to develop more co-morbidities, and as returning veterans seek care for service-related problems, higher spending on chronic conditions will become a more prominent issue for the VA health care system. PMID- 22044351 TI - Radicals formed in N-acetylproline by electron attachment: electron spin resonance spectroscopy and computational studies. AB - In this study, the reactions of electrons with N-acetylproline are investigated by electron spin resonance (ESR) spectroscopy and density functional theory. Electrons are produced by gamma irradiation or by photoionization of K(4)Fe(CN)(6) in neutral 7.5 M LiCl-D(2)O aqueous glasses at low temperatures with identical results. Electrons are found to add to both the peptide bond and the carboxyl group of the acetyl-proline moiety at 77 K. On annealing, both the electron adducts undergo fragmentation of the peptide bond between the nitrogen and the alpha carbon of the peptide structure. However, the peptide bond electron adduct radical reacts much more rapidly than the carboxyl group electron adduct radical. The DFT calculations predict that the carboxyl adduct is substantially more stable than the peptide bond adduct, with the activation barrier to N-Calpha cleavage 3.7 kcal/mol for the amide electron adducts and 23 kcal/mol for the carboxyl electron adducts in inagreement with the relative reactivity found by experiment. PMID- 22044353 TI - Nasopharyngeal prostaglandin E(2) in infant bronchiolitis. AB - The mechanism by which severe bronchiolitis can result in the development of recurrent childhood wheeze is unclear. However, mucosal inflammation and immune activation may play a major role. Prostaglandin (PG) E(2) has been highlighted as a possible therapeutic target for both the treatment of bronchiolitis and the prevention of subsequent airway hyperresponsiveness. The aim of this pilot study was to examine PGE(2) in the airways of infants hospitalised with bronchiolitis. Nasopharyngeal aspirates (NPA) were collected from 18 infants within 12 hours of admission and assayed by enzyme immunoassays for PGE(2), interleukin (IL)-10, and IL-12, as well as cyclooxygenase (COX) 1 and 2 activity. NPA PGE(2) concentration correlated with length of illness preadmission, but was not related to disease severity, causal virus, or IL-10. NPA COX 1 and 2 activity and IL-12 were all below the level of detection. Neither NPA PGE(2) nor disease severity was related to development of recurrent wheeze over 3 years following bronchiolitis. These data suggest that nasopharygeal PGE(2) at hospital admission may be neither directly causal or diagnostic of severity of infant bronchiolitis, or prognostic of development of recurrent wheeze. However, large-cohort temporal examinations are required to adequately define this mediator as a therapeutic target for bronchiolitis. PMID- 22044352 TI - Interleukin-23: as a drug target for autoimmune inflammatory diseases. AB - Interleukin-23 (IL-23) is a member of the IL-12 family of cytokines with pro inflammatory properties. Its ability to potently enhance the expansion of T helper type 17 (Th17) cells indicates the responsibility for many of the inflammatory autoimmune responses. Emerging data demonstrate that IL-23 is a key participant in central regulation of the cellular mechanisms involved in inflammation. Both IL-23 and IL-17 form a new axis through Th17 cells, which has evolved in response to human diseases associated with immunoactivation and immunopathogeny, including bacterial or viral infections and chronic inflammation. Targeting of IL-23 or the IL-23 receptor or IL-23 axis is a potential therapeutic approach for autoimmune diseases including psoriasis, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. The current review focuses on the immunobiology of IL-23 and summarizes the most recent findings on the role of IL-23 in the pre-clinical and ongoing clinical studies. PMID- 22044354 TI - The role of micafungin and anidulafungin in the treatment of systemic fungal infections: applications and patents for two novel echinocandins. AB - Fungal infections are becoming an increasing menace in the hospital care setting. Among them, non-albicans Candida species have gained significant attention. Especially in the ICU setting, therapeutic options are limited in many cases by the side-effects of conventional antifungal therapy. Echinocandins are a relatively new class of antifungal agents that promise good effectiveness against Candida and Aspergillus species. Due to their underlying mechanisms of action, they yield good tolerability and few limitations of usage. In the current manuscript we describe the patents of two recently approved echinocandins, micafungin (US approved 2005) and anidulafungin (2006) and provide an overview of the mechanisms, clinical effectiveness and safety of antifungal therapy with these agents. PMID- 22044355 TI - Antimicrobial activity of carvacrol: current progress and future prospectives. AB - During the last few years the scientific community has shown a considerable interest in the study of plant materials as sources of new compounds to be processed into antimicrobial agents. In this context, carvacrol, a monoterpenic phenol, has emerged for its wide spectrum activity extended to food spoilage or pathogenic fungi, yeast and bacteria as well as human, animal and plant pathogenic microorganisms including drug-resistant and biofilm forming microorganisms. The antibacterial activity of carvacrol has been attributed to its considerable effects on the structural and functional properties of cytoplasmatic membrane. The data reported in this review provide an overview of the published literature regarding the antimicrobial properties of carvacrol and the recent patents claimed in order to highlight its future applications as a new antimicrobial agent. These could concern either the natural preservation in the cosmetic and food industries or an alternative which supports the conventional antimicrobial protocols. Interestingly, carvacrol alone or associated with one or more synergistic products could be incorporated in different formulations for biomedical and food packaging applications. However, more detailed safety investigations and in vivo studies should be carried out so that this molecule could be used in the future. PMID- 22044356 TI - Current and emerging antivirals for the treatment of cytomegalovirus (CMV) retinitis: an update on recent patents. AB - Cytomegalovirus (CMV) retinitis is the most common ocular opportunistic complication and a serious cause of vision loss in immunocompromised patients. Even though, a rise in human immunodeficiency virus (HIV) infected individuals seems to be a major factor responsible for the prevalence of CMV retinitis, the introduction of highly active antiretroviral therapy (HAART) significantly reduced the incidence and severity of CMV retinitis. Thorough evaluation of the patient's immune status and an exact classification of the retinal lesions may provide better understanding of the disease etiology, which would be necessary for optimizing the treatment conditions. Current drugs such as ganciclovir, valganciclovir, cidofovir and foscarnet have been highly active against CMV, but prolonged therapy with these approved drugs is associated with dose-limiting toxicities thus limiting their utility. Moreover development of drug-resistant mutants has been observed particularly in patients with acquired immunodeficiency syndrome (AIDS). Continuous efforts by researchers in the industry and academia have led to the development of newer candidates with enhanced antiviral efficacy and apparently minimal side effects. These novel compounds can suppress viral replication and prevent reactivation in the target population. Though some of the novel therapeutics possess potent viral inhibitory activity, these compounds are still in stages of clinical development and yet to be approved. This review provides an overview of disease etiology, existing anti-CMV drugs, advances in emerging therapeutics in clinical development and related recent patents for the treatment of CMV retinitis. PMID- 22044357 TI - Insights into airway infections by enterococci: a review. AB - Enterococcus is an uncommon but emerging agent of upper and lower airway diseases, including sinuses, trachea, bronchi, lung and pleural infections. In particular, pneumonia and thoracic empyema may jeopardize the clinical outcome of compromised, hospitalized hosts, as well as affect outpatients. Treatment may feel the effects of inherent and acquired resistances such organisms show to commonly used drugs, with the spread of glycopeptide/vancomycin resistant enterococci (GRE/VRE, respectively) being of serious concern. With this work, we want to unearth the impact of members of the genus in the ambit of respiratory infections, and to increase the consciousness of their role as resourceful pathogens for human airways. Also, we are revising patents of interest aiming to timely screen GRE and soon provide clinicians with speciation and glycopeptide resistances. PMID- 22044358 TI - Modulation of ligand-field parameters by heme ruffling in cytochromes c revealed by EPR spectroscopy. AB - Electron paramagnetic resonance (EPR) spectra of variants of Hydrogenobacter thermophilus cytochrome c(552) (Ht c-552) and Pseudomonas aeruginosa cytochrome c(551) (Pa c-551) are analyzed to determine the effect of heme ruffling on ligand field parameters. Mutations introduced at positions 13 and 22 in Ht c-552 were previously demonstrated to influence hydrogen bonding in the proximal heme pocket and to tune reduction potential (E(m)) over a range of 80 mV [Michel, L. V.; Ye, T.; Bowman, S. E. J.; Levin, B. D.; Hahn, M. A.; Russell, B. S.; Elliott, S. J.; Bren, K. L. Biochemistry 2007, 46, 11753-11760]. These mutations are shown here to also increase heme ruffling as E(m) decreases. The primary effect on electronic structure of increasing heme ruffling is found to be a decrease in the axial ligand-field term Delta/lambda, which is proposed to arise from an increase in the energy of the d(xy) orbital. Mutations at position 7, previously demonstrated to influence heme ruffling in Pa c-551 and Ht c-552, are utilized to test this correlation between molecular and electronic structure. In conclusion, the structure of the proximal heme pocket of cytochromes c is shown to play a role in determining heme conformation and electronic structure. PMID- 22044359 TI - DNA profiling of Stenotrophomonas maltophilia by PCR targeted to its species specific repetitive palindromic sequences. AB - AIMS: The aim of this study was to develop a simple protocol for a PCR-based fingerprinting of Stenotrophomonas maltophilia (SmrepPCR) that utilizes primers complementary to repetitive extragenic palindromic elements (REPs) of this micro organism. METHODS AND RESULTS: The relatedness of 34 isolates of environmental and clinical origin was investigated by two SmrepPCRs with two different primers, gyrB sequencing and XbaI macrorestriction followed by pulsed-field gel electrophoresis. While SmrepPCR (with primer DIR) results matched data obtained from the analysis of gyrB nucleotide sequences and identified several clonal complexes, XbaI macrorestriction showed high level of heterogeneity between isolates. The macrorestriction-based clustering of isolates did not correspond to both gyrB and DIR-SmrepPCR grouping. CONCLUSIONS: Our results show that SmrepPCR inferred relationship of isolates is in a good agreement with sequence-based methods. The combined information from all methods used suggests that rapid evolution of S. maltophilia genomes might be predominantly due to high rate of rearrangements caused by mobile genetic elements. SIGNIFICANCE AND IMPACT OF THE STUDY: The presented method is an inexpensive and easy to perform alternative to genotype S. maltophilia isolates and to study their population genetics. SmrepPCR demonstrates the usefulness of species-specific repetitive elements in genomic analyses. PMID- 22044360 TI - Refractory symptoms successfully treated with leukotriene inhibition in a child with systemic mastocytosis. AB - Montelukast was effective in treating refractory abdominal and urinary symptoms in a child with systemic mastocytosis. PMID- 22044361 TI - Galactolipid deficiency in the early pathogenesis of neuronal ceroid lipofuscinosis model Cln8mnd : implications to delayed myelination and oligodendrocyte maturation. AB - AIMS: CLN8 deficiency underlies one of a group of devastating childhood neurodegenerative disorders, the neuronal ceroid lipofuscinoses. The function of the CLN8 protein is currently unknown, but a role in lipid metabolism has been proposed. In human CLN8 diseased brains, alterations in lipid composition have been detected. To further investigate the connection of CLN8 to lipid metabolism, we characterized the lipid composition of early symptomatic Cln8-deficient mouse (Cln8(mnd)) brains. METHODS: For lipid profiling, Cln8(mnd) cerebral cortical tissue was analysed by liquid chromatography/mass spectrometry. Galactolipid synthesis was measured through enzyme activity and real-time mRNA expression analyses. Based on the findings, myelination and white matter integrity were studied by immunohistochemistry, stereological methods, electron microscopy and magnetic resonance imaging. The development of myelin-forming oligodendrocytes was also studied in vitro. RESULTS: Sphingolipid profiling showed a selective reduction in myelin-enriched galactolipids. The mRNA expression and activity of UDP-galactose:ceramide galactosyltransferase (CGT), the key enzyme in the galactolipid synthesis, was reduced in the Cln8(mnd) brain. Expression of oligodendrocyte markers suggests a maturation defect. The amount of myelin was reduced in 1-month-old Cln8(mnd) mice, but reached normal levels by 5 months of age. The level of Cln8 gene expression followed the developmental pattern of myelin formation and was high in primary oligodendrocytes. CONCLUSIONS: Taken together, these observations suggest that galactolipid deficiency and delayed myelin maturation characterize the early CLN8 disease pathogenesis through a maturation defect of oligodendrocytes. PMID- 22044363 TI - Minicraniotomy versus bur holes for evacuation of chronic subdural collections in infants-a preliminary single-institution experience. AB - OBJECT: Various surgical interventions have been described to evacuate chronic subdural collections (CSCs) of infancy. These include transfontanel percutaneous aspiration, subdural drains, placement of bur hole(s) with or without a subdural drain, and shunting. Shunt placement typically provides good long-term success (resolution of the subdural fluid), but comes with well-known early and late complications. Recently, the authors have used a mini-osteoplastic craniotomy technique with the goal of definitively treating these children with a single surgery while avoiding the many issues associated with a shunt. They describe their procedure and compare it with the traditional bur hole technique. METHODS: In this single-institution retrospective study, the authors evaluated 26 cases involving patients who underwent treatment for CSC. Preoperative, intraoperative, and postoperative data were reviewed, including radiographic findings (density of the subdural fluid and ventricular and subarachnoid space size), neurological examination findings, and intraoperative fluid description. The primary outcome was treatment failure, defined as the patient requiring any subsequent surgical intervention after the index procedure (minicraniotomy or bur hole placement). RESULTS: Fifteen patients (10 male and 5 female; median age 5.1 months) collectively underwent 27 minicraniotomy procedures (each procedure representing a hemisphere that was treated). In the bur hole group, there were 11 patients (6 male and 5 female; median age 4.6 months) with 18 hemispheres treated. Both groups had subdural drains placed. The average follow-up for each treatment group was just over 7 months. Treatment failure occurred in 2 patients (13%) in the minicraniotomy group compared with 5 patients (45%) in the bur hole group (p = 0.09). Furthermore, the 2 patients who had treatment failure in the minicraniotomy group required 1 subsequent surgery each, whereas the 5 in the bur hole group needed a total of 9 subsequent surgeries. Eventually, 80% of the patients in the minicraniotomy group and 70% of those in the bur hole group had resolution of the subdural collections on the last imaging study. CONCLUSIONS: The minicraniotomy technique may be a superior technique for the treatment of CSCs in infants compared with bur hole evacuation. The minicraniotomy provides greater visualization of the subdural space and allows more aggressive evacuation of the fluid, better irrigation of the space, the ability to fenestrate any accessible membranes safely, and continued egress of fluid into the subgaleal space. Although this preliminary report has obvious limitations, evaluation of this technique may be worthy of a prospective, multiinstitutional collaborative effort. PMID- 22044364 TI - Treatment practices for Chiari malformation type I with syringomyelia: results of a survey of the American Society of Pediatric Neurosurgeons. AB - OBJECT: The purpose of this study was to report the results of a survey of the American Society of Pediatric Neurosurgeons (ASPN) on treatment of Chiari malformation Type I (CM-I) with syringomyelia. METHODS: A questionnaire was circulated during the 2006 meeting of the ASPN, in which surgeons were surveyed on their management of patients with CM-I and syringomyelia. The survey consisted of questions about 4 clinical scenarios, common causes of surgical failures, and complications. RESULTS: There were 72 respondents, representing more than 90% of attendees at the 2006 ASPN meeting and approximately half of the society's members. The majority of respondents (85%) reported that they perform posterior fossa decompression as first-line treatment for CM-I with syringomyelia. Seven percent perform bony decompression alone, 36% open the dura, and 27% shrink the tonsils. Very few respondents indicated that they offer syrinx drainage as first line therapy (< 3%). Although all respondents reported that they treat symptomatic CM-I/syringomyelia patients surgically, 15% of respondents indicated that they do not operate on asymptomatic patients. Finally, respondents stated that their most common complications are pseudomeningocele and chemical meningitis. CONCLUSIONS: This survey, given to a representative group of experienced North American pediatric neurosurgeons, confirms that posterior fossa decompression is still the preferred treatment modality in children with CM-I and syringomyelia, regardless of symptoms. Although most surgeons open the dura, preferred techniques for decompression vary. In contrast to the results of past surveys, conservative follow-up is now only used by a minority of respondents and only in the asymptomatic patient, and primary syrinx drainage seems to have lost popularity. A multicenter trial of surgical outcomes has been designed based on the information from this survey. PMID- 22044365 TI - Sudden onset of Chiari malformation Type I in previously asymptomatic patients. AB - Chiari malformation Type I (CM-I) is usually suspected in patients with slowly progressing neurological symptoms. However, in some instances, especially if syringomyelia is associated, an abrupt clinical onset is reported and is accompanied by an acknowledged risk of potentially severe clinical signs or even sudden death. Little is known about such a critical course in CM-I/syringomyelia complex. The authors describe 3 challenging cases of the abrupt onset of CM I/syringomyelia to reveal more information on the clinical presentation and pathogenetic mechanisms of this sudden and potentially severe clinical phenomenon: a 38-year-old man experienced acute respiratory failure requiring intubation following acute decompensation of hydrocephalus associated with Noonan syndrome, a 1-year-old boy had sudden hemiparesis and Horner syndrome after a minor head/neck injury, and a 2.5-year-old boy presented with quickly progressing tetraplegia and dyspnea after a mild flexion and extension neck injury a few hours before. All 3 patients showed a CM-I/syringomyelia complex at diagnosis, and all of them had a good neurological outcome after surgery despite the ominous clinical presentation. PMID- 22044366 TI - Unreliability of intraoperative estimated blood loss in extended sagittal synostectomies. AB - OBJECT: Intraoperative blood loss represents a significant concern during open repair of craniosynostosis, and its reliable measurement remains a serious challenge. In this study of extended sagittal synostectomies, the authors analyzed the relationship between estimated blood loss (EBL) and calculated blood loss (CBL), and investigated predictors of hemodynamic outcomes. METHODS: The authors reviewed outcomes in infants with sagittal synostosis who underwent primary extended synostectomies (the so-called Pi procedure) between 1997 and 2009. Patient demographic data, operating time, and mean arterial pressures (MAPs) were recorded. Serial MAPs were averaged for a MAP(mean). The EBL was based on anesthesia records, and the CBL on pre- and postoperative hemoglobin values in concert with transfusion volumes. Factors associated with EBL, CBL, red blood cell transfusion (RBCT), and hospital length of stay (LOS) were investigated. Hemodynamic outcomes were reported as percent estimated blood volume (% EBV), and relationships were analyzed using simple and multiple linear and logistic regression models. A p value < 0.05 was considered significant. RESULTS: Seventy-one infants with sagittal synostosis underwent primary extended synostectomies at a mean age and weight of 4.9 months and 7.3 kg, respectively. The average operating time was 1.4 hours, and intraoperative MAP was 54.6 mm Hg (21.3% lower than preoperative baseline). There was no association between mean EBL (12.7% EBV) and mean CBL (23.6% EBV) (r = 0.059, p = 0.63). The EBL inversely correlated with the patient's age (r = -0.07) and weight (r = -0.11) at surgery (p < 0.05 in both instances). With regard to intraoperative factors, EBL positively trended with operating time (r = 0.26, p = 0.09) and CBL inversely trended with MAP(mean) (r = -0.04, p = 0.10), although these relationships were only borderline significant. Intraoperative RBCT, which was required in 59.1% of patients, positively correlated with EBL (r = 1.55, p < 0.001), yet negatively trended with CBL (r = -0.40, p = 0.01). Undertransfusion was significantly more common than overtransfusion (40.8% vs 22.5%, p = 0.02, respectively). The mean hospital LOS was 2.3 days and was not significantly associated with patient demographic characteristics, intraoperative factors, blood loss, RBCT, or total fluid requirements. CONCLUSIONS: In extended synostectomies for sagittal synostosis, EBL and CBL demonstrated a decided lack of correlation with one another. Intraoperative blood transfusion positively correlated with EBL, but inversely correlated with CBL, with a significantly higher proportion of patients undertransfused than overtransfused. These findings highlight the need for reliable, real-time monitoring of intraoperative blood loss to provide improved guidance for blood and fluid resuscitation. PMID- 22044367 TI - Craniosynostosis following hemispherectomy in a 2.5-month-old boy with intractable epilepsy. AB - The authors report on the case of a 6-week-old boy who presented with infantile spasms. At 2.5 months of age, the patient underwent a right hemispherectomy. Approximately 3 months postoperatively, the patient presented with left coronal craniosynostosis. Subsequent cranial vault remodeling resulted in satisfactory cosmesis. Four years after surgery, the patient remains seizure free without the need for anticonvulsant medications. The authors believe this to be the first reported case of iatrogenic craniosynostosis due to hemispherectomy, and they describe 2 potential mechanisms for its development. This case suggests that, in the surgical treatment of infants with intractable epilepsy, minimization of brain volume loss through disconnection techniques should be considered, among other factors, when determining the best course of action. PMID- 22044369 TI - Spontaneous intracranial hemorrhage and multiple intracranial aneurysms in a patient with Roberts/SC phocomelia syndrome. AB - Roberts/SC phocomelia syndrome (RBS) is a rare but distinct genetic disorder with an autosomal recessive inheritance pattern. It has been associated with microcephaly, craniofacial malformation, cavernous hemangioma, encephalocele, and hydrocephalus. There are no previously reported cases of RBS with intracranial aneurysms. The authors report on a patient with a history of RBS who presented with a spontaneous posterior fossa hemorrhage. Multiple small intracranial aneurysms were noted on a preoperative CT angiogram. The patient underwent emergency craniotomy for evacuation of the hemorrhage. A postoperative angiogram confirmed the presence of multiple, distal small intracranial aneurysms. PMID- 22044368 TI - Left thorascopic sympathectomy for refractory long QT syndrome in children. AB - Congenital long QT syndrome (LQTS) is a rare genetic ion transmembrane disorder that has been associated with multiple various genetic mutations including life threatening cardiac arrhythmias and sudden death. Left thorascopic sympathectomy is an effective treatment for patients who are refractory to medical therapy or who need frequent epicardial internal cardiodefibrillator intervention. Although there is substantial literature about this therapy in adults, few reports detail the outcomes in children who undergo left thorascopic sympathectomies to treat LQTS. The authors report the successful use of a left thoracic sympathectomy for the treatment of an 11-year-old girl who had persistently symptomatic LQTS, even after implantation of an automatic cardioverter-defibrillator. The patient remained clinically stable without arrhythmias through 6 months' of follow-up. The authors also reviewed the relevant literature and found that it suggests that 77% of patients will have immediate resolution of their symptoms/arrhythmias after the procedure. When the outcome definition was broadened to include patients who had only 1 or 2 cardiac episodes in the follow-up period, 88% of cases were considered successful. The results of this case study and literature review suggest that left thorascopic sympathectomy is a safe and effective approach for treating pediatric patients with LQTS. PMID- 22044370 TI - Freehand placement of depth electrodes using electromagnetic frameless stereotactic guidance. AB - The presurgical evaluation of patients with epilepsy often requires an intracranial study in which both subdural grid electrodes and depth electrodes are needed. Performing a craniotomy for grid placement with a stereotactic frame in place can be problematic, especially in young children, leading some surgeons to consider frameless stereotaxy for such surgery. The authors report on the use of a system that uses electromagnetic impulses to track the tip of the depth electrode. Ten pediatric patients with medically refractory focal lobar epilepsy required placement of both subdural grid and intraparenchymal depth electrodes to map seizure onset. Presurgical frameless stereotaxic targeting was performed using a commercially available electromagnetic image-guided system. Freehand depth electrode placement was then performed with intraoperative guidance using an electromagnetic system that provided imaging of the tip of the electrode, something that has not been possible using visually or sonically based systems. Accuracy of placement of depth electrodes within the deep structures of interest was confirmed postoperatively using CT and CT/MR imaging fusion. Depth electrodes were appropriately placed in all patients. Electromagnetic-tracking-based stereotactic targeting improves the accuracy of freehand placement of depth electrodes in patients with medically refractory epilepsy. The ability to track the electrode tip, rather than the electrode tail, is a major feature that enhances accuracy. Additional advantages of electromagnetic frameless guidance are discussed. PMID- 22044371 TI - Treatment of a supratentorial primitive neuroectodermal tumor using magnetic resonance-guided laser-induced thermal therapy. AB - Supratentorial primitive neuroectodermal tumors (PNETs) are rare tumors that carry a poorer prognosis than those arising from the infratentorial compartment (such as medulloblastoma). The overall prognosis for these patients depends on several factors including the extent of resection, age at diagnosis, CSF dissemination, and site in the supratentorial space. The authors present the first case of a patient with a newly diagnosed supratentorial PNET in which cytoreduction was achieved with MR-guided laser-induced thermal therapy. A 10 year-old girl presented with left-sided facial weakness and a large right thalamic mass extending into the right midbrain. The diagnosis of supratentorial PNET was made after stereotactic biopsy. Therapeutic options for this lesion were limited because of the risks of postoperative neurological deficits with resection. The patient underwent MR-guided laser-induced thermal ablation of her tumor. Under real-time MR thermometry, thermal energy was delivered to the tumor at a core temperature of 90 degrees C for a total of 960 seconds. The patient underwent follow-up MR imaging at regular intervals to evaluate the tumor response to the thermal ablation procedure. Initial postoperative scans showed an increase in the size of the lesion as well as the amount of the associated edema. Both the size of the lesion and the edema stabilized by 1 week and then decreased below preablation levels at the 3-month postsurgical follow-up. There was a slight increase in the size of the lesion and associated edema at the 6-month follow-up scan, presumably due to concomitant radiation she received as part of her postoperative care. The patient tolerated the procedure well and has had resolution of her symptoms since surgery. Further study is needed to assess the role of laser-induced thermal therapy for the treatment of intracranial tumors. As such, it is a promising tool in the neurosurgical armamentarium. Postoperative imaging has shown no evidence of definitive recurrence at the 6-month follow-up period, but longer-term follow-up is required to assess for late recurrence. PMID- 22044373 TI - Lateral posterior fossa encephalocele with associated migrational disorder of the cerebellum in an infant. AB - Encephaloceles are acquired or congenital defects in which intracranial contents protrude through a defect in the calvaria. The embryogenesis of these lesions is incompletely understood. The vast majority of lesions occur at or near the anatomical midline. The authors present an extremely rare case of a laterally oriented, pathologically proven encephalocele associated with a posterior fossa cyst and cerebellar migrational defect in an infant. The authors review past and current theories of encephalocele formation as it relates to this case. PMID- 22044372 TI - Variation in the BRCA2 gene in a child with medulloblastoma and a family history of breast cancer. AB - The fact that BRCA genes operate as tumor suppressors is evident from the genetics of the different human disorders caused by inherited mutations. Germline mutations affecting 1 allele of either BRCA1 or BRCA2 confer susceptibility to different types of cancers such as breast cancer and medulloblastoma. A family with a history of cancer was identified in Eastern Turkey in which one of the family members (a 13-year-old boy) had medulloblastoma. Venous blood was collected from available family members. The BRCA1 and BRCA2 genes were sequenced in the patient with medulloblastoma and the healthy father. An Asn372His homozygous variation was noted in the BRCA2 gene in the patient with medulloblastoma whereas the variation was heterozygous in the healthy father. A biallelic homozygous variation was demonstrated in the BRCA2 gene, which is important in medulloblastoma suppression, and may have caused medulloblastoma formation in the 13-year-old boy. Further investigations in large human populations with medulloblastoma are necessary for further delineation of BRCA gene malfunctions and their relationship to medulloblastoma formation, and to clarify the therapeutic implications of these malfunctions. PMID- 22044374 TI - Endoscopic fenestrations for suprasellar arachnoid cysts. AB - OBJECT: The endoscopic treatment of a suprasellar arachnoid cyst (SAC) consists mainly of ventriculocystostomy (VC) and ventriculocystocisternostomy (VCC). However, the most appropriate treatment for these cysts has not been fully determined yet. The authors report on the effectiveness of endoscopic VC for SACs communicating with the basal cisterns, which is demonstrated by preoperative CT cisternography. METHODS: The authors retrospectively analyzed the surgical results of patients with an SAC treated using endoscopic fenestration. The patient charts were reviewed for demographic data, clinical presentations, surgical therapies, and clinical outcomes. RESULTS: Six consecutive patients with SAC were surgically treated using endoscopic fenestration (VC or VCC) between March 2004 and February 2011. The mean age was 18.5 months (range 5 days to 37 months). Five patients were previously untreated, and 1 patient had previously undergone ventriculoperitoneal shunt placement. Five patients underwent preoperative CT cisternography, and communication between the SAC and the basal cisterns was demonstrated in 3 patients, very slight communication in 1, and no communication in 1. Four patients, including the 3 with communication between the SAC and basal cisterns, underwent VC. Two patients with very slight or no communication underwent VCC. In all patients the SAC decreased in size and hydrocephalus improved postoperatively. Five patients (3 treated with VC and 2 with VCC [83%]) have been stable without reoperation (mean follow-up 32.7 months). All 3 patients with an SAC communicating with the basal cisterns have been stable without reoperation following VC. CONCLUSIONS: Preoperative cisternography may be useful for selecting the optimal endoscopic treatment method for SAC. If an SAC communicates with the basal cisterns, a VC could be an effective, safe, and simpler treatment option. PMID- 22044375 TI - Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus: validation of a success score that predicts long-term outcome. AB - OBJECT: The goal of this study was to externally validate the proposed Endoscopic Third Ventriculostomy Success Score (ETVSS), which predicts successful treatment for hydrocephalus on the basis of a child's individual characteristics. METHODS: The authors retrospectively identified 181 cases of consecutive endoscopic third ventriculostomy (ETV) performed in children at a single neurosurgery center in the United Kingdom. They compared actual success at both 6 and 36 months, with mean predicted probabilities for low, moderate, and high chance of success strata based on the ETVSS. Long-term success was calculated using Kaplan-Meier methods and comparisons were made by means of unpaired t-tests. RESULTS: Overall, 166 primary ETVs were performed; ETV success was 72.9% at 6 and 64.5% at 36 months. At long-term follow-up, the mean predicted probability of success was significantly higher in those with a successful ETV (99 patients) than in those with a failed ETV (67 patients) (p = 0.001). The ETVSS accurately predicted outcome at 36 months; the low, medium, and high chance of success strata had mean predicted probabilities of success of 82%, 63%, and 36%, and actual success of 76%, 66%, and 42%, respectively. The overall complication rate was 6%. CONCLUSIONS: The ETVSS closely predicted the overall long-term success rates in high-, moderate-, and low-risk groups. The results of this study suggest that the ETVSS will aid clinical decision making in predicting outcome of ETV. PMID- 22044376 TI - Evaluating the Children's Hospital of Alabama endoscopic third ventriculostomy experience using the Endoscopic Third Ventriculostomy Success Score: an external validation study. AB - OBJECT: Endoscopic third ventriculostomy (ETV) success is dependent on patient characteristics including age, origin of hydrocephalus, and history of shunt therapy. Using these factors, an Endoscopic Third Ventriculostomy Success Score (ETVSS) model was constructed to predict success of therapy. This study reports a single-institution experience with ETV and explores the ETVSS model validity. METHODS: A retrospective chart review identified 151 consecutive patients who underwent ETV at a pediatric hospital between August 1995 and December 2009. Of these 151, 136 patients had at least 6 months of clinical follow-up. Data concerning patient characteristics, operative characteristics, radiological findings, complications, and success of ETV were collected. The actual success rates were compared with those predicted by the ETVSS model. RESULTS: The actual success rate of ETV at 6 months was 68.4% (93 of 136 patients), which compared well to the predicted ETVSS of 76.5% +/- 12.5% (+/- SD). The C-statistic was 0.74 (95% CI 0.65-0.83), suggesting that the ability of the ETVSS to discriminate failures from successes was good. Secondary ETV was found to have a hazard ratio for failure of 4.2 (95% CI 2.4-7.2) compared with primary ETV (p < 0.001). The complication rate was 9.3% with no deaths. At the first radiological follow-up, the increased size of ventricles had a hazard ratio for failure of 3.0 (95% CI 1.5-6.0) compared with patients in whom ventricle size either remained stable or decreased (p = 0.002). CONCLUSIONS: The ETVSS closely predicts the actual success of ETV, fitting the statistical model well. Shortcomings of the model were identified in overestimating success in patients with ETVSS <= 70, which may be attributable to the poor success of secondary ETVs in the authors' patient population. PMID- 22044378 TI - Costs and benefits of neurosurgical intervention for infant hydrocephalus in sub Saharan Africa. AB - OBJECT: Evidence from the CURE Children's Hospital of Uganda (CCHU) suggests that treatment for hydrocephalus in infants can be effective and sustainable in a developing country. This model has not been broadly supported or implemented due in part to the absence of data on the economic burden of disease or any assessment of the cost and benefit of treatment. The authors used economic modeling to estimate the annual cost and benefit of treating hydrocephalus in infants at CCHU. These results were then extrapolated to the potential economic impact of treating all cases of hydrocephalus in infants in sub-Saharan Africa (SSA). METHODS: The authors conducted a retrospective review of all children initially treated for hydrocephalus at CCHU via endoscopic third ventriculostomy or shunt placement in 2005. A combination of data and explicit assumptions was used to determine the number of times each procedure was performed, the cost of performing each procedure, the number of disability-adjusted life years (DALYs) averted with neurosurgical intervention, and the economic benefit of the treatment. For CCHU and SSA, the cost per DALY averted and the benefit-cost ratio of 1 year's treatment of hydrocephalus in infants were determined. RESULTS: In 2005, 297 patients (median age 4 months) were treated at CCHU. The total cost of neurosurgical intervention was $350,410, and the cost per DALY averted ranged from $59 to $126. The CCHU's economic benefit to Uganda was estimated to be between $3.1 million and $5.2 million using a human capital approach and $4.6 million-$188 million using a value of a statistical life (VSL) approach. The total economic benefit of treating the conservatively estimated 82,000 annual cases of hydrocephalus in infants in SSA ranged from $930 million to $1.6 billion using a human capital approach and $1.4 billion-$56 billion using a VSL approach. The minimum benefit-cost ratio of treating hydrocephalus in infants was estimated to be 7:1. CONCLUSIONS: Untreated hydrocephalus in infants exacts an enormous price from SSA. The results of this study suggest that neurosurgical intervention has a cost/DALY averted comparable to other surgical interventions that have been evaluated, as well as a favorable benefit-cost ratio. The prevention and treatment of hydrocephalus in SSA should be recognized as a major public health priority. PMID- 22044377 TI - Five-year survival and outcome of treatment for postinfectious hydrocephalus in Ugandan infants. AB - OBJECT: Neonatal infection is the most common cause of infant hydrocephalus in Uganda. Postinfectious hydrocephalus (PIH) is often accompanied by primary brain injury from the original infection. Since 2001, ETV (with or without choroid plexus cauterization) has been our primary treatment for PIH. The long-term outcome in these children is unknown. METHODS: We studied the 5-year outcome in a cohort of 149 infants treated for PIH from 2001 to 2005 and who lived in 4 districts close to the hospital. Survival analysis was performed using the Kaplan Meier method. Statistical significance was determined using the Fisher, Breslow, and log-rank tests. RESULTS: The patients' mean age at presentation was 9.5 months (median 3.0 months). Eighty-four patients (56.4%) were successfully treated without a shunt. Operative mortality was 1.2% for ETV and 4.4% for shunt placement (p = 0.3). Five-year survival was 72.8% in the non-shunt-treated group and 67.6% in the shunt-treated group, with no difference in survival (log rank p = 0.43, Breslow p = 0.46). Of 43 survivors assessed at 5-11 years, those with shunts had significantly worse functional outcomes (p = 0.003-0.035), probably reflecting treatment selection bias since those with the worst sequelae of ventriculitis were more likely to be treated with shunt placement. CONCLUSIONS: Nearly one-third of treated infants died within 5 years, and at least one-third of the survivors were severely disabled. There was no survival advantage for non shunt-treated patients at 5 years. A randomized trial of endoscopic third ventriculostomy versus shunt placement for treating PIH may be indicated. Public health measures that prevent these infections are urgently needed. PMID- 22044379 TI - Effective surgical treatment of cerebral cavernous malformations: a multicenter study of 79 pediatric patients. AB - OBJECT: Cerebral cavernous malformations (CCMs) are common vascular lesions in the brain, affecting approximately 0.5% of the population and representing 10% 20% of all cerebral vascular lesions. One-quarter of all CCMs affect pediatric patients, and CCMs are reported as one of the main causes of brain hemorrhage in this age group. Symptoms include epileptic seizures, headache, and focal neurological deficits. Patients with symptomatic CCMs can be treated either conservatively or with resection if lesions cause medically refractory epilepsy or other persistent symptoms. METHODS: The authors retrospectively analyzed 79 pediatric patients (41 boys and 38 girls) from 3 different centers, who were surgically treated for their symptomatic CCMs between 1974 and 2004. The mean age of the children at first manifestation was 9.7 years, and the mean age at operation was 11.3 years. The main goal was to compare the clinical outcomes with respect to the location of the lesion of children who preoperatively suffered from epileptic seizures. RESULTS: Of these patients, 77.3% were seizure free (Engel Class I) after the resection of the CCM. Significant differences in the outcome between children who harbored CCMs at different locations were not found. CONCLUSIONS: Resection seems to be the favorable treatment of symptomatic CCMs not only in adults but also in children. PMID- 22044380 TI - A sacral hydatid cyst mimicking an anterior sacral meningocele. AB - Hydatid disease is a zoonosis caused by Echinococcus granulosus. It is a progressive disease with serious morbidity risks. Sacral hydatid disease is very uncommon, accounting for < 11% of spinal hydatidosis cases. The diagnosis of a sacral hydatid cyst is sometimes difficult because hydatidosis can simulate other cystic pathologies. The authors report on 9-year-old boy admitted to their service with a paraparesis that allowed walking without aid. The boy presented with a 2-year history of an evolving incomplete cauda equina syndrome as well as a soft cystic mass in the abdomen extending from the pelvis. Radiological examination revealed an anterior meningocele. A posterior approach with laminectomy from L-5 to S-3 was performed. Three lesions with classic features of a hydatid cyst were observed and removed. The diagnosis of hydatid cyst was confirmed histopathologically. Antihelmintic treatment with albendazole (15 mg/kg/day) was included in the postoperative treatment. The patient's condition improved after surgery, and he recovered normal mobility. The unusual site and presentation of hydatid disease in this patient clearly supports the consideration of spinal hydatid disease in the differential diagnosis for any mass in the body, especially in endemic areas. PMID- 22044381 TI - Traumatic tiger attack. AB - Attacks on humans by large cats are uncommon occurrences and thus the principles of managing such injuries are not well documented. The authors here report the case of an 11-year-old boy who was mauled by a privately owned tiger. The attack resulted in multiple cranial lacerations and fractures, dissection of the internal carotid artery, and persistent neurological deficits. This case outlines the multiple sources of injury and pathology that can result from such an attack. Discussion is focused on the pattern of injury seen in large feline attacks and the treatment approach. PMID- 22044382 TI - Posterior reversible encephalopathy syndrome. PMID- 22044384 TI - Allogeneic donor peripheral blood "stem cell" apheresis: prospective comparison of two apheresis systems. AB - BACKGROUND: Granulocyte-colony-stimulating factor-mobilized peripheral blood stem cells, collected by white blood cell apheresis, are used for more than 80% of allogeneic and most autologous hematopoietic stem cell transplantations. Optimal donor and recipient outcomes require maximized stem cell collection efficiency and minimized non-target cell contamination. Therefore, improved apheresis technology is desirable. The safety and feasibility of apheresis collections with the novel, electronics-assisted apheresis system Spectra Optia v.5.0 (CaridianBCT) were recently demonstrated. An unpublished optimization trial had furthermore determined that different settings than manufacturer-installed default might result in improved apheresis yields. STUDY DESIGN AND METHODS: The first prospective comparison of allogeneic peripheral blood stem cell apheresis with the Spectra Optia versus the COBE Spectra (CaridianBCT) mononuclear cell (MNC) in a routine clinical setting is reported here; "optimized" machine settings were used. Assessed variables included collection efficiency, product characteristics, donor outcomes, and frequency of operator interventions. Outcomes were additionally compared with historical data from the Spectra Optia in default mode. RESULTS: The mean CD34+ cell collection efficiency CE1 was 7.9% greater with the Spectra Optia than with the COBE Spectra MNC. Variability of outcomes was equally great. Reduced platelet (PLT) attrition necessitated 90% fewer autologous PLT reinfusions. Spectra Optia products contained 50% fewer red blood cells, but 50% more granulocytic lineage cells. Less operator input was required, although 26% of Spectra Optia apheresis procedures required triggering of the first chamber flush. Apheresis yield and collection efficiency were also markedly greater than in default-mode Spectra Optia collections. CONCLUSION: Using optimized machine settings, peripheral blood stem cell apheresis outcomes with the automated apheresis system Spectra Optia exceed results with the COBE Spectra MNC or the Spectra Optia in the default mode. PMID- 22044385 TI - An in vitro biofilm model for enamel demineralization and antimicrobial dose response studies. AB - Microcosm biofilms formed in microplates have demonstrated complex community dynamics similar to natural dental biofilm. No simplified microcosm models to evaluate enamel demineralization and dose-response effect to anticariogenic therapies have yet been established, thus this study was designed to develop a pre-clinical model fulfilling this purpose. Experiments were carried out to establish the time of biofilm formation and the sucrose concentration and exposure regimen. Biofilms were initiated from saliva and grown for up to 10 days on bovine enamel discs in 24-well plates, with a saliva analogue medium. Data were collected as pH readings and the percentage enamel surface hardness change. A dose-response evaluation was performed with chlorhexidine, which significantly affected the pH and mineral loss. Overall, the established model parameters, 5 days of biofilm growth with intermittent 1% sucrose exposure of 6 h per day, was suitable as a pre-clinical model for enamel demineralization and dose-response studies. PMID- 22044386 TI - Spinal cord injury. PMID- 22044387 TI - Discovery of salt taste enhancing arginyl dipeptides in protein digests and fermented fish sauces by means of a sensomics approach. AB - As enzymatic digests of fish proteins were recently reported to enhance salt taste, the fish protein protamine was digested by chymotrypsin and trypsin and subsequently screened for candidate salt taste modulating (STM) peptides. To achieve this, first, a two-step sensory assay was developed and demonstrated to be a rather suitable tool for the detection of salt taste enhancers and the "quantitation" of their salt taste enhancing activity on the basis of isointensities with reference solutions. By means of activity-guided fractionation using ultrafiltration, gel permeation chromatography, and hydrophilic liquid interaction chromatography in combination with the sensory assay for STM activity assessment, a series of arginyl dipeptides, with RP, RA, AR, RG, RS, RV, VR, and RM being the most active, as well as l-arginine were found as salt taste enhancing molecules in fish protamine digests. For the first time, HPLC-MS/MS analysis on a PFP and a HILIC stationary phase, respectively, enabled the quantitative analysis of the arginyl peptides in a series of commercial and laboratory-made protein hydrolysates as well as fermented fish sauces. PMID- 22044388 TI - Surface heterogeneity on hemispheres-in-cell model yields all experimentally observed non-straining colloid retention mechanisms in porous media in the presence of energy barriers. AB - Many mechanisms of colloid retention in porous media under unfavorable conditions have been identified from experiments or theory, such as attachment at surface heterogeneities, wedging at grain to grain contacts, retention via secondary energy minimum association in zones of low flow drag, and straining in pore throats too small to pass. However, no previously published model is capable of representing all of these mechanisms of colloid retention. In this work, we demonstrate that incorporation of surface heterogeneity into our hemispheres-in cell model yields all experimentally observed non-straining retention mechanisms in porous media under unfavorable conditions. We also demonstrate that the predominance of any given retention mechanism depends on the coupled colloid collector-flow interactions that are governed by parameters such as the size and spatial frequency of heterogeneous attractive domains, colloid size, and solution ionic strength. The force/torque balance-simulated retention is shown to decrease gradually with decreasing solution ionic strength, in agreement with experimental observations. This gradual decrease stands in sharp contrast to predictions from mean field theory that does not account for discrete surface heterogeneity. PMID- 22044390 TI - Fear, numbers, and measles. PMID- 22044389 TI - Do multiple concurrent infections in African children cause irreversible immunological damage? AB - Much of the developing world, particularly sub-Saharan Africa, has high levels of morbidity and mortality associated with infectious diseases. The greatest risk of invasive disease is in the young, the malnourished and HIV-infected individuals. In many regions in Africa these vulnerable groups and the wider general population are under constant immune pressure from a range of environmental factors, under-nutrition and multiple concurrent infections from birth through to adulthood. Intermittent microbial exposure during childhood is required for the generation of naturally acquired immunity capable of protection against a range of infectious diseases in adult life. However, in the context of a resource-poor setting, the heavy burden of malarial, diarrhoeal and respiratory infections in childhood may subvert or suppress immune responses rather than protect, resulting in sub-optimal immunity. This review will explore how poor maternal health, HIV exposure, socio-economic and seasonal factors conspire to weaken childhood immune defences to disease and discuss the hypothesis that recurrent infections may drive immune dysregulation, leading to relative immune senescence and premature immunological aging. PMID- 22044392 TI - Unusual adsorption site behavior in PCN-14 metal-organic framework predicted from Monte Carlo simulation. AB - The adsorption equilibrium of methane in PCN-14 was simulated by the Monte Carlo technique in the grand canonical ensemble. A new force field was proposed for the methane/PCN-14 system, and the temperature dependence of the molecular siting was investigated. A detailed study of the statistics of the center of mass and potential energy showed a surprising site behavior with no energy barriers between weak and strong sites, allowing open metal sites to guide methane molecules to other neighboring sites. Moreover, this study showed that a model assuming weakly adsorbing open metal clusters in PCN-14, densely populated only at low temperatures (below 150 K), can explain published experimental data. These results also explain previously observed discrepancies between neutron diffraction experiments and Monte Carlo simulations. PMID- 22044393 TI - Reversal of Hall-Petch effect in structural stability of PbTe nanocrystals and associated variation of phase transformation. AB - Using an in situ synchrotron X-ray diffraction technique, a pressure-induced phase transformation of PbTe nanocrystals with sizes of 13 and 5 nm up to ~20 GPa was studied. Upon an increase of pressure, we observed that the 13 nm PbTe nanocrystals start a phase transformation from rocksalt structure to an intermediate orthorhombic structure and finally CsCl-type structure at 8 GPa, which is 2 GPa higher than that in bulk PbTe. In contrast, the 5 nm PbTe nanocrystals do not display the same type of transition with a further increased transition pressure as expected. Instead of orthorhombic or CsCl-type structure, the 5 nm PbTe nanocrystals turn to amorphous phase under a similar pressure (8 GPa). Upon a release of pressure, the 13 nm PbTe nanocrystals transform from high pressure CsCl-type structure directly to rocksalt structure, whereas the 5 nm PbTe nanocrystals remain their amorphous phase to ambient conditions. The structure stability of rocksalt-type PbTe shows a significant reversal of Hall Petch effect. On the basis of such an observation with a critical size determination of ~9 nm, PbTe nanocrystals appear as the first class of material that demonstrates a pressure-induced structural change from order to disorder. By sharing the insight of this reversed Hall-Petch effect with associated transition types, we tuned our experimental protocol and successfully synthesized a sample with "high-pressure metastable structure", amorphous phase at ambient pressure. This integrative study provides a feasible pathway to understand nucleation mechanism as a function of particle size and to explore novel materials with high pressure metastable structure and unique properties under lab-accessible conditions. PMID- 22044397 TI - Modulation of glucokinase by glucose, small-molecule activator and glucokinase regulatory protein: steady-state kinetic and cell-based analysis. AB - GK (glucokinase) is an enzyme central to glucose metabolism that displays positive co-operativity to substrate glucose. Small-molecule GKAs (GK activators) modulate GK catalytic activity and glucose affinity and are currently being pursued as a treatment for Type 2 diabetes. GK progress curves monitoring product formation are linear up to 1 mM glucose, but biphasic at 5 mM, with the transition from the lower initial velocity to the higher steady-state velocity being described by the rate constant kact. In the presence of a liver-specific GKA (compound A), progress curves at 1 mM glucose are similar to those at 5 mM, reflecting activation of GK by compound A. We show that GKRP (GK regulatory protein) is a slow tight-binding inhibitor of GK. Analysis of progress curves indicate that this inhibition is time dependent, with apparent initial and final Ki values being 113 and 12.8 nM respectively. When GK is pre-incubated with glucose and compound A, the inhibition observed by GKRP is time dependent, but independent of GKRP concentration, reflecting the GKA-controlled transition between closed and open GK conformations. These data are supported by cell-based imaging data from primary rat hepatocytes. This work characterizes the modulation of GK by a novel GKA that may enable the design of new and improved GKAs. PMID- 22044391 TI - Accumulation of B1-like B cells in transgenic mice over-expressing catalytically inactive RAG1 in the periphery. AB - During their development, B lymphocytes undergo V(D)J recombination events and selection processes that, if successfully completed, produce mature B cells expressing a non-self-reactive B-cell receptor (BCR). Primary V(D)J rearrangements yield self-reactive B cells at high frequency, triggering attempts to remove, silence, or reprogramme them through deletion, anergy induction, or secondary V(D)J recombination (receptor editing), respectively. In principle, expressing a catalytically inactive V(D)J recombinase during a developmental stage in which V(D)J rearrangement is initiated may impair this process. To test this idea, we generated transgenic mice expressing a RAG1 active site mutant (dnRAG1 mice); RAG1 transcript was elevated in splenic, but not bone marrow, B cells in dnRAG1 mice relative to wild-type mice. The dnRAG1 mice accumulate splenic B cells with a B1-like phenotype that exhibit defects in B-cell activation, and are clonally diverse, yet repertoire restricted with a bias toward Jkappa1 gene segment usage. The dnRAG1 mice show evidence of impaired B cell development at the immature-to-mature transition, immunoglobulin deficiency, and poorer immune responses to thymus-independent antigens. Interestingly, dnRAG1 mice expressing the anti-dsDNA 3H9H56R heavy chain fail to accumulate splenic B1 like cells, yet retain peritoneal B1 cells. Instead, these mice show an expanded marginal zone compartment, but no difference is detected in the frequency of heavy chain gene replacement. Taken together, these data suggest a model in which dnRAG1 expression impairs secondary V(D)J recombination. As a result, selection and/or differentiation processes are altered in a way that promotes expansion of B1-like B cells in the spleen. PMID- 22044398 TI - Effect of guaifenesin on mucin production, rheology, and mucociliary transport in differentiated human airway epithelial cells. AB - Guaifenesin is widely used to alleviate symptoms of excessive mucus accumulation in the respiratory tract. However, its mechanism of action is poorly understood. The authors hypothesized that guaifenesin improves mucociliary clearance in humans by reducing mucin release, by decreasing mucus viscoelasticity, and by increasing mucociliary transport. To test these hypotheses, human differentiated airway epithelial cells, cultured at an air-liquid interface, were treated with clinically relevant concentrations of guaifenesin by addition to the basolateral medium. To evaluate the effect on mucin secretion, the authors used an anzyme linked immunosorbent assay (ELISA) to measure the amounts of MUC5AC protein in apical surface fluid and cell lysates. To measure mucociliary transportability, additional cultures were treated for 1 or 6 hours with guaifenesin, and the movement of cell debris was measured from video data. Further, the authors measured mucus dynamic viscoelasticity using a micro cone and plate rheometer with nondestructive creep transformation. Guaifenesin suppressed mucin production in a dose-dependent manner at clinically relevant concentrations. The reduced mucin production was associated with increased mucociliary transport and decreased viscoelasticity of the mucus. Viability of the cultures was not significantly affected. These results suggest that guaifenesin could improve mucociliary clearance in humans by reducing the release and/or production of mucins, thereby altering mucus rheology. PMID- 22044399 TI - Structure of geminal imidazolium bis(trifluoromethylsulfonyl)imide dicationic ionic liquids: a theoretical study of the liquid phase. AB - In this work, we report molecular dynamics simulations of the bulk liquid phase of geminal di-imidazolium bis(trifluoromethylsulfonyl)imide ionic liquids. We characterize a few interesting features of the local structure in the liquid phase, and we make a comparison both with gas phase structures and with the monoimidazolic counterparts. We analyze in detail the diffraction properties of these fluids by simulating X-ray and neutron scattering factors and we report on the long-range structural order that seems to also arise in one of these compounds. PMID- 22044400 TI - Functional equivalence and spatial path memory. AB - Loomis, Klatzky, Avraamides, Lippa and Golledge ( 2007 ) suggest that, when it comes to spatial information, verbal description and perceptual experience are nearly functionally equivalent with respect to the cognitive representations they produce. We tested this idea for the case of spatial memory for complex paths. Paths consisted entirely of unit-length segments followed by 90-degree turns, thus assuring that a path could be described with equal precision using either an egocentric verbal description or a virtual self-motion experience. The verbal description was analogous to driving directions (e.g., turn left and go one block, then turn right, etc.) except in three dimensions (allowing rotation followed by up or down movement). Virtual self-motion was depicted as first person travel through a 3D grid of featureless corridors. Comparison of these two conditions produced a result that may be surprising to some, but nevertheless appears to support the notion of functional equivalence: Virtual self-motion does not produce better path memory than verbal description, when care is taken to present equally precise path information. This result holds for even very complex paths and despite evidence from proximity-based interference that the memory representation of the path is spatial. PMID- 22044401 TI - Investigation of the configurational stabilities of chiral isocyanoacetates in multicomponent reactions. AB - Isocyanoacetates are uniquely reactive compounds characterized by an ambivalent isocyano functional group and an enolizable alpha-carbon. It is widely believed that chiral alpha-substituted isocyanoacetates are configurationally unstable in some synthetically useful isocyanide-based multicomponent reactions. Herein, we demonstrate that chiral isocyanoacetates can be used with minimal to negligible epimerization in a variety of canonical Ugi four-component condensations as well as Joullie-Ugi three-component condensations, reactions that are particularly useful for constructing complex peptide structures in a single synthetic operation. PMID- 22044402 TI - Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects. AB - AIMS To evaluate the pharmacology and tolerability of PF-04457845, an orally available fatty acid amide hydrolase-1 (FAAH1) inhibitor, in healthy subjects. METHODS: Double-blind, randomized, placebo-controlled single and multiple rising dose studies and an open-label, randomized, food effect study were conducted. Plasma and urine PF-04457845 concentrations, plasma fatty acid amide concentrations and FAAH1 activity in human leucocytes were measured. Tolerability, including effects on cognitive function, were assessed. RESULTS: PF 04457845 was rapidly absorbed (median t(max) 0.5-1.2 h). Exposure increased supraproportionally to dose from 0.1 to 10 mg and proportionally between 10 and 40 mg single doses. The pharmacokinetics appeared dose proportional following 14 days once daily dosing between 0.5 and 8 mg. Steady-state was achieved by day 7. Less than 0.1% of the dose was excreted in urine. Food had no effect on PF 04457845 pharmacokinetics. FAAH1 activity was almost completely inhibited (>97%) following doses of at least 0.3 mg (single dose) and 0.5 mg once daily (multiple dose) PF-04457845. Mean fatty acid amide concentrations increased (3.5- to 10 fold) to a plateau and then were maintained following PF-04457845. FAAH1 activity and fatty acid amide concentrations returned to baseline within 2 weeks following cessation of dosing at doses up to 4 mg. There was no evidence of effects of PF 04457845 on cognitive function. PF-04457845, at doses up to 40 mg single dose and 8 mg once daily for 14 days, was well tolerated. CONCLUSIONS: PF-04457845 was well tolerated at doses exceeding those required for maximal inhibition of FAAH1 activity and elevation of fatty acid amides. PMID- 22044403 TI - Real time three-dimensional transthoracic echocardiography in congenital heart disease. AB - Diagnosing congenital heart disease (CHD) depends heavily on imaging. Traditionally, two-dimensional (2D) echocardiography has been the most widely used but since this imaging modality utilizes a 2D technique to evaluate three dimensional (3D) structures it suffers from inherent limitations. The more recently developed 3D echocardiography is poised to be superior in providing comprehensive evaluation prior to intervention on such complex conditions. In this review, we summarize the applications of 3D echocardiography in evaluating patients with CHD. PMID- 22044404 TI - Detection of extended-spectrum beta-lactamase-producing Escherichia coli isolates in faecal samples of Iberian lynx. AB - AIMS: To characterize the diversity of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli isolates recovered within the faecal microbiota of Iberian lynx. The identification of other associated resistance genes and the analysis of clonal relationship were also focused in this study. METHODS AND RESULTS: From 2008 to 2010, 128 faecal samples of Iberian lynx (wild and captive animals) were collected. Eleven tested samples contained cefotaxime-resistant E. coli isolates (all belonging to captive animals) and 10 ESBL-producing isolates were showed. CTX-M-14 and SHV-12 ESBL-types were detected and seven different patterns were identified by pulsed-field gel electrophoresis analysis. CONCLUSIONS: The occurrence of unrelated multiresistant E. coli in faecal flora of captive specimens of Iberian lynx, including the presence of ESBLs, resistant genes in integrons and virulence determinants was showed in this study. SIGNIFICANCE AND IMPACT OF THE STUDY: The results obtained in this study highlight the environmental problem as future reintroductions of Iberian lynx could lead to a spread of resistant bacteria. Additionally, ESBL-producing bacteria can represent a health problem for this endangered species. PMID- 22044405 TI - Effectiveness of a palliative care outpatient programme in improving cancer related symptoms among ambulatory Brazilian patients. AB - The focuses of palliative care are to provide symptom relief and improve quality of life through an interdisciplinary approach. Previous studies conducted to evaluate the effectiveness of palliative care in reducing symptom distress among outpatients confirmed the importance of the palliative care approach. To our knowledge, there is no published information from Brazil regarding the impact of a palliative care outpatient programme in reducing symptom distress. Symptom scores from 232 patients were measured using Edmonton Symptom Assessment System scales in two consecutive consults. Changes in symptoms at follow-up visit were analysed using Wilcoxon signed-rank paired test. The symptom subtraction indices (SSI) (follow-up scores minus baseline scores) were calculated and then analysed with Spearman's correlation. Edmonton Symptom Assessment System median scores at follow-up visits were statistically significant reduced in all symptoms evaluated. All the SSI positively correlated with well-being-SSI. Other important SSI correlations were: fatigue-SSI and anxiety-SSI, and fatigue-SSI and dyspnoea SSI. Our palliative care outpatient programme was able to provide a significant improvement in the symptoms evaluated. The well-being-SSI was positively correlated with all the SSI, verifying that the control of symptoms in palliative care is essential for the patient well-being. Adequate/inadequate control of specifically symptoms seems to indirectly improve/worsen other symptoms. PMID- 22044406 TI - Oxygen plasma treated interactive polycarbonate DNA microarraying platform. AB - A novel DNA microarrying platform based on oxygen plasma activation of polycarbonate surface of compact disks (DVD) is presented. Carboxylic acid groups are generated in few seconds on polycarbonate in an efficient, fast, and clean way. Following this surface activation strategy, amino-modified oligonucleotide probes were covalently attached, reaching an immobilization density of 2 pmol cm( 2). Atomic force microscopy imaging revealed the nondestructive character of this treatment when applied for short times, allowing for disk scanning in standard DVD drives. DNA assays performed on oxygen plasma treated disks resulted very efficient with maximum hybridization yield of 93% and reaching a low limit of detection (200 pM) for perfect match synthetic oligonucleotide targets when reading the disk with a standard drive as detector. The approach was also evaluated by scoring single nucleotide polymorphisms with a discrimination ratio of 12.8. As proof of concept, the oxygen plasma treated interactive polycarbonate DNA microarraying platform was applied to the detection of PCR products of Salmonella spp., reaching a detection limit of 2 nM that corresponds to a DNA concentration of only 1 c.f.u./mL. The results confirm the suitability of the microarray platform for analysis of biological samples with high sensitivity. PMID- 22044407 TI - Synthesis and characterization of a 1-D porous barium carboxylate coordination polymer, [Ba(HBTB)] (H3BTB = benzene-1,3,5-trisbenzoic acid). AB - The synthesis and characterization of [Ba(HBTB)] is reported. This is the first porous framework synthesized with barium using carboxylate ligands. The framework has robust microporous character (Langmuir surface area of 879 m(2) g(-1)) and possesses unsaturated metal sites when fully desolvated. PMID- 22044408 TI - Symmetrical drug-related intertriginous and flexural exanthema (baboon syndrome) induced by amoxicillin-clavulanate. AB - Systemic drug-related intertriginous and flexural exanthema (SDRIFE), also known as Baboon syndrome, is an uncommon, cutaneous reaction that occurs after the systemic administration of drug-related allergens. We report the case of a 5-year old boy with SDRIFE after systemic administration of amoxicillin-clavulanate. PMID- 22044409 TI - Future of the pharmacogenomics of calcineurin inhibitors in renal transplant patients. PMID- 22044410 TI - Pharmacogenomics of psychotropic drugs. PMID- 22044412 TI - Prediction of tumor response to chemoradiotherapy by genetic profile in rectal cancer patients. PMID- 22044413 TI - Personal account of the discovery of a new disease using next-generation sequencing. Interview by Natalie Harrison. PMID- 22044414 TI - Genetic and genomic predictors of anti-TNF response. AB - The introduction of anti-TNF therapy has dramatically improved the outlook for patients suffering from a number of inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease. Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment response is likely to be multifactorial; however, variation in genes or their expression may identify those most likely to respond. By targeted testing of variants within candidate genes, potential predictors of anti-TNF response have been reported; however, very few markers have replicated consistently between studies. Emerging genome-wide association studies suggest that there may be a number of genes with modest effects on treatment response rather than a few genes of large effect. Other potential serum biomarkers of response have also been explored including cytokines and autoantibodies, with antibodies developing to the anti-TNF drugs themselves being correlated with treatment failure. PMID- 22044415 TI - Polymorphisms, hypertension and thiazide diuretics. AB - It is 10 years since the discovery of the human genome; however, the study of the influence of genetic variants on drug effect - pharmacogenomics - has so far failed to create a major impact on day-to-day prescription practices. In the present article we analyze the main findings in candidate gene variants, gene combinations and whole-genome scans in relation to diuretic treatment. A critical analysis of the main reasons for some contrasting results will be discussed. The hypertension phases, in clinical trials dealing with genes and related pathophysiological mechanisms, may account for these inconsistent findings. The use of previously untreated versus treated patients is addressed. Finally, a positive study with a new genetic molecular strategy is described. PMID- 22044416 TI - Statin dose in Asians: is pharmacogenetics relevant? AB - Historically the efficacy and safety of statins has mostly been studied in western populations. Few such studies have been carried out in Asians until recent years. These studies revealed interesting similarities and differences for statin use between Asians and Caucasians. One clinically important question subsequently raised is whether Asians need lower statin doses compared with Caucasians. Many practicing physicians believe that statin doses are lower in Asians because of the generally lower bodyweight and BMI. Whether this belief is based on sound scientific evidence needs to be reviewed. Furthermore, since the decision of optimal dose is based on both efficacy and safety, both of which may be impacted by genetic factors, one may ask whether pharmacogenetics plays a role in the dose difference, if such a difference exists. There is a clinical need to critically and comprehensively article the literature to answer these questions, and summarize future directions of research in the field. This article serves the above purpose. PMID- 22044417 TI - Detection and characterization of the CYP2D6*9x2 gene duplication in two Spanish populations: resolution of AmpliChip CYP450 test no-calls. AB - BACKGROUND: CYP2D6 is a major drug-metabolizing enzyme. Polymorphic variation includes copy number variants such as gene deletions, duplications and multiplications of functional and nonfunctional gene units. In this article we describe the first systematic characterization of a CYP2D6*9x2 gene duplication. CYP2D6*9 is an allelic variant conferring reduced enzymatic activity. This novel gene duplication was discovered in two unrelated Spanish psychiatric patients. Both subjects were initially tested with the AmpliChip CYP450 test, which indicated the presence of a duplication and the CYP2D6*9 allele, but did not make a genotype call. The goal of the study was to resolve this issue by characterizing the CYP2D6 gene locus in these patients. MATERIALS & METHODS: Both individuals and one offspring were regenotyped using our own CYP2D6 genotyping strategy employing long-range PCR and TaqMan-based SNP detection. In addition, gene resequencing and genotyping of duplication-specific long-range PCR products and quantitative gene copy number analysis was applied. RESULTS: The duplication was mapped to the CYP2D6*9 allele and copy number analysis determined a CYP2D6*9x2 gene duplication in all three individuals. Because CYP2D6*9x2 is not recognized by the AmpliChip CYP450 test, this structural arrangement was responsible for the 'no call' on the AmpliChip CYP450 test report. CONCLUSION: The full characterization of this allele will aid in the interpretation of AmpliChip CYP450 test results for clinical and research applications. Original submitted 8 June 2011; Revision submitted 18 July 2011. PMID- 22044419 TI - Catalytic itinerary in 1,3-1,4-beta-glucanase unraveled by QM/MM metadynamics. Charge is not yet fully developed at the oxocarbenium ion-like transition state. AB - Retaining glycoside hydrolases (GHs), key enzymes in the metabolism of polysaccharides and glycoconjugates and common biocatalysts used in chemoenzymatic oligosaccharide synthesis, operate via a double-displacement mechanism with the formation of a glycosyl-enzyme intermediate. However, the degree of oxocarbenium ion character of the reaction transition state and the precise conformational itinerary of the substrate during the reaction, pivotal in the design of efficient inhibitors, remain elusive for many GHs. By means of QM/MM metadynamics, we unravel the catalytic itinerary of 1,3-1,4-beta-glucanase, one of the most active GHs, belonging to family 16. We show that, in the Michaelis complex, the enzyme environment restricts the conformational motion of the substrate to stabilize a (1,4)B/(1)S(3) conformation of the saccharide ring at the -1 subsite, confirming that this distortion preactivates the substrate for catalysis. The metadynamics simulation of the enzymatic reaction captures the complete conformational itinerary of the substrate during the glycosylation reaction ((1,4)B/(1)S(3) -(4)E/(4)H(3) - (4)C(1)) and shows that the transition state is not the point of maximum charge development at the anomeric carbon. The overall catalytic mechanism is of dissociative type, and proton transfer to the glycosidic oxygen is a late event, clarifying previous kinetic studies of this enzyme. PMID- 22044421 TI - Interface engineering in high-performance low-voltage organic thin-film transistors based on 2,7-dialkyl-[1]benzothieno[3,2-b][1]benzothiophenes. AB - We investigated two different (2,7-dialkyl-[1]benzothieno[3,2 b][1]benzothiophenes; C(n)-BTBT-C(n), where n = 12 or 13) semiconductors in low voltage operating thin-film transistors. By choosing functional molecules in nanoscaled hybrid dielectric layers, we were able to tune the surface energy and improve device characteristics, such as leakage current and hysteresis. The dipolar nature of the self-assembled molecules led to a shift in the threshold voltage. All devices exhibited high charge carrier mobilities of 0.6-7.0 cm(2) V( 1) s(-1). The thin-film morphology of BTBT was studied by means of atomic force microscopy (AFM), presented a dependency upon the surface energy of the self assembled monolayer (SAM) hybrid dielectrics but not upon the device performance. The use of C(13)-BTBT-C(13) on hybrid dielectrics of AlO(x) and a F(15)C(18) phosphonic acid monolayer led to devices with a hole mobility of 1.9 cm(2) V(-1) s(-1) at 3 V, on/off ratio of 10(5), small device-device variation of mobility, and a threshold voltage of only -0.9 V, thus providing excellent characteristics for further integration. PMID- 22044420 TI - Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection. AB - Typhoid fever is a persistent infection caused by host-adapted Salmonella strains adept at circumventing immune-mediated host defences. Given the importance of T cells in protection, the culling of activated CD4+ T cells after primary infection has been proposed as a potential immune evasion strategy used by this pathogen. We demonstrate that the purging of activated antigen-specific CD4+ T cells after virulent Salmonella infection requires SPI-2 encoded virulence determinants, and is not restricted only to cells with specificity to Salmonella expressed antigens, but extends to CD4+ T cells primed to expand by co-infection with recombinant Listeria monocytogenes. Unexpectedly, however, the loss of activated CD4+ T cells during Salmonella infection demonstrated using a monoclonal population of adoptively transferred CD4+ T cells was not reproduced among the endogenous repertoire of antigen-specific CD4+ T cells identified with MHC class II tetramer. Analysis of T-cell receptor variable segment usage revealed the selective loss and reciprocal enrichment of defined CD4+ T-cell subsets after Salmonella co-infection that is associated with the purging of antigen-specific cells with the highest intensity of tetramer staining. Hence, virulent Salmonella triggers the selective culling of high avidity activated CD4+ T-cell subsets, which re-shapes the repertoire of antigen-specific T cells that persist later after infection. PMID- 22044422 TI - The human immunodeficiency virus-1 genotype diversity and drug resistance mutations profile of volunteer blood donors from Chinese blood centers. AB - BACKGROUND: The global human immunodeficiency virus (HIV)-1 epidemic is becoming increasingly diverse and complex. Molecular epidemiologic characteristics were studied for HIV-1-infected blood donors from five Chinese regions to determine genotype diversity and drug resistance mutations (DRMs) profile. STUDY DESIGN AND METHODS: HIV-1 confirmed-reactive serum samples were collected from 172 blood donors from five blood centers during 2007 to 2010. HIV-1 Pol including whole protease and partial reverse transcriptase genes was amplified, sequenced, and analyzed for the subtype determination and drug resistance profile description. RESULT: A total of 113 amplified sequences including 82 from Kunming blood center and 31 from four other blood centers had the following genotype characteristics: G (0.9%), B (2.7%), circulating recombinant form (CRF) 01_AE (32.7%), CRF07_BC (22.1%), and CRF08_BC (41.6%). Female donors represent 45.1% of all cases and 63.9% cases with DRMs. The prevalence of samples with potential low or higher resistance among Chinese blood donors is 4.4%. CONCLUSION: HIV-1 infection in Chinese blood donors is genetically diverse and the subtype distribution reflects that from the high-risk populations. Our results support continuous molecular epidemiologic surveillance for HIV-1 in blood donors as a part of a comprehensive HIV control program. PMID- 22044423 TI - A study of politeness strategies adopted in pediatric clinics in Taiwan. AB - Drawing on Brown and Levinson's (1987) politeness theory, this study investigates the communicative interaction behaviors of physicians, patients, and patients' parents in pediatrics in Taiwan. Thirty outpatients and six senior physicians from three different levels of hospital participated in the study. The analysis results indicate that most of the communicative politeness strategies used in pediatrics are bald-on-record, direct, and non-redressed. In addition, physicians adopt a higher percentage of bald-on-record and negative politeness strategies than patients. In contrast, patients' parents use more positive politeness and off-record strategies. These results indicate that while physicians display lower levels of politeness and often communicate directly, patients' parents express more supportive opinions and adopt more indirect communication strategies. The results reveal a preference for efficiency in pediatric clinics, with physicians adopting a dominant role in the communication process. These results also demonstrate an inherently asymmetric power balance between physician and patient. Our findings indicate the presence of several commonly seen politeness strategies and dialogue patterns that encourage greater self-awareness and self-observation for physicians and patients, leading to more effective communication in the clinical context. Finally, also discussed are the possible influences of Chinese culture such as face work, harmony, and power. PMID- 22044424 TI - Meeting the need for regenerative therapies I: target-based incidence and its relationship to U.S. spending, productivity, and innovation. AB - Regenerative therapies possess high theoretical potential for medical advance yet their success as commercial therapeutics is still open to debate. Appropriate data on target opportunities that provide perspective and enable strategic decision making is necessary for both efficient and effective translation. Up until now, this data have been out of reach to research scientists and many start up companies-the very groups currently looked to for the critical advance of these therapies. The target-based estimate of opportunity presented in this report demonstrates its importance in evaluating medical need and technology feasibility. In addition, analysis of U.S. research spending, productivity, and innovation reveals that U.S. basic research in this field would benefit from greater interdisciplinarity. Overcoming the barriers that currently prevent translation into high value therapies that are quickly clinically adopted requires simultaneous integration of engineering, science, business, and clinical practice. Achieving this integration is nontrivial. PMID- 22044425 TI - B-type natriuretic peptide levels at birth predict cardiac dysfunction in neonates. AB - BACKGROUND: Although the B-type natriuretic peptide (BNP) levels in the umbilical cord blood (UCB-BNP) and amniotic fluid (AF-BNP) of neonates may be clinically useful for identifying newborns with cardiac dysfunction, the effects of various clinical factors, such as gestational age at birth, small for gestational age (SGA), and neonatal asphyxia, on the UCB-BNP and AF-BNP levels have not been studied extensively. METHODS: The present study sought to determine whether the UCB-BNP and AF-BNP levels can predict cardiac dysfunction and hypotension in preterm infants soon after birth and to evaluate the association between BNP and various clinical factors. The UCB-BNP and AF-BNP levels at birth were determined in 320 and 195 neonates, respectively, born to mothers with singleton pregnancies. RESULTS: The UCB-BNP and AF-BNP levels in infants treated with dopamine were significantly higher than those in infants without dopamine administration (230.1 vs 33.1 pg/mL and 74.4 vs 18.1 pg/mL, respectively). Stepwise multiple regression analyses indicated that gestational age, SGA, asphyxia, and chorioamnionitis were significant independent determinants of the UCB-BNP level. Cut-off values of >90 pg/mL for UCB-BNP and >36 pg/mL for AF-BNP yielded sensitivities of 68% and 93%, respectively, and specificities of 84% and 81%, respectively, for detecting neonates who required dopamine administration after birth. CONCLUSION: High UCB-BNP and AF-BNP levels predict neonatal cardiac dysfunction soon after birth. PMID- 22044426 TI - Design, synthesis, structure, and acaricidal/insecticidal activity of novel spirocyclic tetronic acid derivatives containing an oxalyl moiety. AB - A series of novel spirocyclic tetronic acid derivatives containing an oxalyl moiety was designed and synthesized via the key intermediate 3-(2,4,6-trimethyl) 2-oxo-1-oxaspiro[4.4]-decyl-3-en-4-ol. The target compounds were identified by (1)H NMR and elemental analysis or high-resolution mass spectrum (HRMS). The results of bioassays indicated that most of the target compounds possessed excellent acaricidal activities against carmine spider mite larvae and eggs. Especially, diisopropylamino oxalyl compound 7g and piperidine oxalyl compound 7h were 1.4- and 2.3-fold as high as the activities of commercial Spiromesifen, respectively, against spider mite eggs. Moreover, most of the target compounds exhibited insecticidal activities against Lepidoptera pest. Interestingly, compounds containing alkylamino-substituted oxalyl moiety showed obvious selectivity between spider mite larvae and eggs because the activities against spider mite eggs of 7g and 7h were 25-fold those against spider mite larvae, whereas Spiromesifen had no significant differences in these activities. This meant that the introduction of an oxalyl moiety to spirocyclic tetronic acid might lead to novel biological activity characteristics. PMID- 22044427 TI - B-cell agonists up-regulate AID and APOBEC3G deaminases, which induce IgA and IgG class antibodies and anti-viral function. AB - B cells express two critical deaminases in the development of adaptive and innate immunity. Activation-induced cytidine deaminase (AID) functions in class switch recombination, somatic hypermutation and may result in affinity maturation of antibodies. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G; A3G) is an innate anti-retroviral factor that inhibits HIV replication. We have studied a number of B-cell agonists with the aim of identifying the most effective agents that will up-regulate both deaminases and thereby enhance adaptive and innate immunity. CD40 ligand (CD40L) with interleukin-4 or HLA-class II antibodies significantly up-regulated both AID and A3G in isolated human CD19(+) B cells. The functions of these deaminases were demonstrated by enhancement of B-cell surface expression of IgA and IgG and inducing significantly higher IgA and IgG4 antibodies. An enhanced A3G function was then demonstrated by inhibition of HIV-1 replication in co-culture of CD4(+) T cells with autologous B cells, treated with CD40L and CD4 or HLA antibodies, compared with unstimulated human B cells. The dual B-cell-induced deaminase functions may be critical in IgA and IgG antibodies inhibiting pre-entry and A3G that of post-entry HIV-1 transmission and suggests a novel strategy of immunization, especially relevant to mucosal infections. PMID- 22044428 TI - Clozapine functions through the prefrontal cortex serotonin 1A receptor to heighten neuronal activity via calmodulin kinase II-NMDA receptor interactions. AB - Aberrant dopamine release in the prefrontal cortex (PFC) is believed to underlie schizophrenia, but the mechanistic pathway through which a widely used antipsychotic, clozapine (Clz), evokes neurotransmitter-releasing electrical stimulation is unclear. We analyzed Clz-evoked regulation of neuronal activity in the PFC by stimulating axons in layers IV and V and recording the electrical effect in the post-synaptic pyramidal cells of layers II and III. We observed a Clz-evoked increase in population spike (PS), which was mediated by serotonin 1A receptor (5-HT(1A)-R), phospholipase Cbeta, and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Immunoblotting demonstrated that the Clz-activation of CaMKII was 5-HT(1A)-R-mediated. Intriguingly, the NMDA receptor (NMDA-R) antagonist (+/-)2-amino-5-phosphonovaleric acid (APV) eliminated the Clz-mediated increase in PS, suggesting that the 5-HT(1A)-R, NMDA-R and CaMKII form a synergistic triad, which boosts excitatory post-synaptic potential (EPSP), thereby enhancing PS. In corroboration, Clz as well as NMDA augmented field EPSP (fEPSP), and WAY100635 (a 5-HT(1A)-R antagonist), APV, and a CaMKII inhibitor eliminated this increase. As previously shown, CaMKII binds to the NMDA-R 2B (NR2B) subunit to become constitutively active, thereby inducing alpha-amino-3 hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor recruitment to the post synaptic membrane and an increase in fEPSP. Co-immunoprecipitation demonstrated that Clz potentiates interactions among CaMKII, NR2B, and 5-HT(1A)-R, possibly in the membrane rafts of the post-synaptic density (PSD), because pretreatment with methyl-beta-cyclodextrin (MCD), an agent that disrupts rafts, inhibited both co immunoprecipitation as well as fEPSP. In summary, Clz functions in the PFC by orchestrating a synergism among 5-HT(1A)-R, CaMKII, and NMDA-R, which augments excitability in the PFC neurons of layers II/III. PMID- 22044429 TI - Can junior emergency physicians use E-point septal separation to accurately estimate left ventricular function in acutely dyspneic patients? AB - OBJECTIVES: The authors determined if E-point septal separation (EPSS) as measured by junior emergency physicians (EPs) correlated with visual estimation of left ventricle ejection fraction (LVEF) by senior EPs and cardiologists in acutely dyspneic patients presenting to an adult emergency department (ED). METHODS: Acutely dyspneic patients were enrolled in a prospective, observational study. EPSS was measured using bedside ultrasonography by junior EPs (PGY 3 and PGY 4 residents) with variable ultrasound experience. M-mode measurements of EPSS were recorded in the parasternal long-axis orientation and were calculated during diastole by measuring distance from the tip of the anterior mitral valve leaflet to the septal wall. LVEF was visually estimated at the bedside by emergency medicine (EM) ultrasound fellows and an EM ultrasound fellowship-trained attending physician and was subsequently visually estimated by two cardiologists reviewing video clips obtained by the junior EPs. The correlation between EPSS and visually estimated LVEF was calculated. RESULTS: Of the 58 patients, the median age was 63 years (range = 28 to 90 years) and 66% were women. Interobserver reliability between EPs and cardiologists for the visual estimation of LVEF was excellent (kappa = 0.75). The correlation between measurements of EPSS by junior EPs and visual estimations of LVEF by the senior EPs was rho = 0.844 (p < 0.001). CONCLUSIONS: In this study, junior EPs were able to obtain measurements of EPSS that correlated closely with visual estimates of LVEF by clinicians with extensive point-of-care and comprehensive echocardiography experience. PMID- 22044430 TI - Immune response against serial infusion of factor VIII antigen through an implantable venous-access device system in haemophilia A mice. AB - Haemophilia A is a life long bleeding disorder caused by an inherited deficiency of factor VIII (FVIII). About 30% of haemophilia A patients develop neutralizing antibodies as a consequence of treatment with FVIII concentrates. Immune tolerance protocols for the eradication of inhibitors require daily delivery of intravenous FVIII. We evaluated the immune responses to serial intravenous administration of FVIII in preimmunized haemophilia A mice. We introduced an implantable venous-access device (iVAD) system into haemophilia A mice to facilitate sequential infusion of FVIII. After preimmunization with FVIII, the haemophilia A mice were subjected to serial intravenous administration of FVIII through the iVAD system. In all mice with serial infusion of FVIII, high titers of anti-FVIII inhibitory antibodies developed at 10 exposure days (EDs). However, the anti-FVIII IgG titers were decreased after 150 EDs of sequential low-dose infusion of FVIII [0.05 U g(-1) body weight (BW) five times per week]. Proliferative response to ex vivo FVIII stimulation was significantly suppressed in splenic CD4(+) T cells from mice with serial low-dose FVIII infusion compared with those from mice with high-dose FVIII infusion (0.5 U g(-1) BW five times per week) or preimmunized mice. Moreover, splenic CD4(+) T cells from mice with serial low-dose infusion of FVIII failed to produce interleukin-2 and interferon gamma. These data suggest that serial infusion of FVIII could induce T-cell anergy in haemophilia A mice with inhibitor antibodies. PMID- 22044432 TI - Auto-align - multi-modality fluorescence microscopy image co-registration. AB - Multi-modality microscopes incorporate multiple microscopy techniques into one module, imaging through a common objective lens. Simultaneous or consecutive image acquisition of a single specimen, using multiple techniques, increases the amount of measurable information available. In order to benefit from each modality, it is necessary to accurately co-register data sets. Intrinsic differences in the image formation process employed by each modality result in images which possess different characteristics. In addition, as a result of using different measurement devices, images often differ in size and can suffer relative geometrical deformations including rotation, scale and translation, making registration a complex problem. Current methods generally rely on manual input and are therefore subject to human error. Here, we present an automated image registration tool for fluorescence microscopy. We show that it successfully registers images obtained via total internal reflection fluorescence (TIRF), or epi-fluorescence, and confocal microscopy. Furthermore, we provide several other applications including channel merging following image acquisition through an emission beam splitter, and lateral stage drift correction. We also discuss areas of membrane trafficking which could benefit from application of Auto-Align. Auto Align is an essential item in the advanced microscopist's toolbox which can create a synergy of single or multi-modality image data. PMID- 22044433 TI - Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years. AB - AIMS: To determine efficacy of the analgesic flupirtine in the treatment of overactive bladder syndrome in a proof-of-concept study. METHODS: Double-blind, double-dummy, three-armed comparison of flupirtine extended release (400 mg/day, titrated to 600 mg/day), tolterodine extended release (4 mg/day) and placebo for 12 weeks. RESULTS: When major elevations of liver enzymes (more than three times the upper normal limit) were detected in several flupirtine-exposed patients, the study was prematurely discontinued. Based on study-end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for >= 6 weeks. CONCLUSIONS: Unexpected frequent and relevant toxicity can occur when testing an established drug for a new indication. PMID- 22044434 TI - Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non-muscle-invasive bladder cancer: validation across time and place and recommendation for benchmarking. AB - Study Type - Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Apart from bladder tumour multiplicity, size, stage, grade and presence of cis, early recurrence following white light TURBT for new bladder tumours is also determined by surgeon experience, completeness of resection and presence or absence of detrusor muscle in the specimen. This study aims to validate surgeon experience and detrusor muscle as independent predictors of early recurrence following apparently complete white light TURBT in new bladder tumours. OBJECTIVE: To validate in patients undergoing first transurethral resection of bladder tumour (TURBT) for non-muscle-invasive bladder cancer (NMIBC), the presence/absence of detrusor muscle (DM) in the specimen and surgeon experience as independent predictors of the quality of TURBT. PATIENTS AND METHODS: Patients with new NMIBC, who had undergone complete first resections were recruited from a prospectively maintained cohort from the 1980s at the Western General Hospital, Edinburgh, UK and a contemporary cohort from the Aberdeen Royal Infirmary, UK. Tumour size, multiplicity, surgeon category, presence or absence of DM in the specimen, grade, stage, findings at first check cystoscopy and early re-TURBT were evaluated. Surgeons were stratified into a senior group (consultant and trainees in year five or six) and a junior group (trainees below year five). Early recurrence, or recurrence rate at the first follow up cystoscopy (RRFFC), was used to measure quality and was defined as finding pathologically confirmed tumour at early re-TURBT or the first check cystoscopy. RESULTS: From a total of 566 patients evaluated from both cohorts, 473 NMIBC specimens were suitable for analysis. Logistic regression multivariate analysis revealed that the absence of DM was associated with a higher RRFFC (odds ratio [OR]= 3.6, 95% CI = 1.7-7.5, P < 0.001). Senior surgeons were more likely to resect DM (OR = 4.9, 95% CI = 2.3-10.7, P < 0.001) Senior surgeons were independently associated with a lower RRFFC (OR = 5.3, 95% CI = 2.1-12.9, P < 0.001). CONCLUSIONS: Detrusor muscle status at the first, apparently complete, TURBT and surgeon's experience independently predict the quality of TURBT. * Documented complete resection by experienced surgeons with DM presence (good quality white-light TURBT) should be considered a benchmark for white-light TURBT in NMIBC. PMID- 22044435 TI - Overexpression of GhSusA1 increases plant biomass and improves cotton fiber yield and quality. AB - Cotton (Gossypium spp.) is an important economic crop and the largest source of textile fiber in the world. However, to date, only a few genes have been identified that exhibit critical roles in fiber development, and few has shown positive effects on fiber yield and quality in transgenic cotton. Here, we report the characterization of a novel sucrose synthase (SusA1) gene from a superior quality fiber germplasm line 7235 in Gossypium hirsutum. By association analysis, GhSusA1 was highly correlated with fiber qualities in (7235* TM-1) recombinant inbred lines based on polymorphism of GhSusA1 between 7235 and TM-1. Subsequently, based on an interspecific population of 141 BC1 individuals generated from the cross between TM-1 and Gossypium barbadense line, Hai7124, we further mapped GhSusA1 genes on homeologous chromosomes A8 (chro.8) and D8 (chro.24). Suppression of GhSusA1 in transgenic cotton reduced fiber quality and decreased the boll size and seed weight. Importantly, overexpression of this gene increased fiber length and strength, with the latter indicated by the enhanced thickening of cell wall during secondary wall formation stage. Moreover, increasing GhSusA1 transcript abundance in vegetative tissues led to elevated seedling biomass. Together, these findings identified GhSusA1 as a key regulator of sink strength in cotton, which is tightly associated with productivity, and hence a promising candidate gene that can be developed to increase cotton fiber yield and quality. PMID- 22044436 TI - Characterization of the tomato prosystemin promoter: organ-specific expression, hormone specificity and methyl jasmonate responsiveness by deletion analysis in transgenic tobacco plants. AB - Tomato systemin is a bioactive peptide that regulates the systemic activation of wound-responsive genes. It is released from its 200 amino acid precursor called prosystemin. Initial tissue-localization and hormone-induced expression assays indicated that the tomato prosystemin gene (SlPS) accumulates mainly in floral tissues and in response to exogenous abscisic acid and methyl jasmonate (MeJA) treatments, respectively. Later, the promoter regions of the PS gene in tomato (Solanum lycopersicum L. cv. Castlemart), pepper (Capsicum annuum) and potato (Solanum tuberosum) were isolated and an in silico analysis of the SlPS promoter revealed an over-representation of stress- and MeJA-responsive motifs. A subsequent 5' deletion analysis of the SlPS promoter fused to the beta glucuronidase reporter (GUS) gene showed that the -221 to +40 bp proximal SlPS promoter region was sufficient to direct the stigma, vascular bundle-specific and MeJA-responsive expression of GUS in transgenic tobacco plants. Important vascular-tissue-specific, light- and MeJA-responsive cis-elements were also present in this region. These findings provide relevant information regarding the transcriptional regulation mechanisms of the SlPS promoter operating in transgenic tobacco plants. They also suggest that its tissue-specificity and inducible nature could have wide applicability in plant biotechnology. PMID- 22044438 TI - Twist angle plays an important role in photophysical properties of a donor acceptor-type conjugated polymer: a combined ensemble and single-molecule study. AB - We investigated photophysical properties of a donor-acceptor-type conjugated polymer by means of ensemble and single-molecule spectroscopy as well as density functional theory (DFT) calculation. The polymer is based on an alkyne-linked 1,8 carbazole (Cz) and possesses a benzothiadiazole (BT) as an electron acceptor moiety. A comparison with model compounds demonstrated that the dimer structure is the spectroscopic unit of the polymer. Single-molecule two-color excitation fluorescence and fluorescence lifetime experiments showed that the polymer molecules displayed broad distributions of fluorescence intensity ratio and fluorescence lifetime. Together with the DFT calculation, we demonstrated that the twist angle between the Cz and BT moieties played a central role in deciding those spectroscopic properties of the polymer. This result was further supported by single-molecule fluorescence spectral measurement. The spectral measurement also suggested intersegment interactions within the single chains. Furthermore, single-molecule defocused and polarization fluorescence imaging suggested efficient exciton migration and trapping occurring within the single polymer chain. These experiments also revealed changes of the lowest energy site within the single polymer molecules. PMID- 22044437 TI - Do cancer patients' psychosocial outcomes and perceptions of quality of care vary across radiation oncology treatment centres? AB - This study aimed to explore whether rates of depression, and anxiety and patient views about quality of patient-centred care varied across four metropolitan radiation therapy treatment centres in Sydney, Australia. Participants were radiation therapy outpatients, aged 18 or older and English-speaking. Participants completed a brief survey by touch screen computer while waiting for their radiation therapy treatment appointment. For eight indicators of patient centred care, participants were asked to indicate whether their well-being would have been improved by better care related to the indicator. Participants also completed the Hospital Anxiety and Depression Scale. No differences between treatment centres were found for rates of anxiety and depression, or for the mean number of domains of care endorsed as needing improvement (indicated by agreeing or strongly agreeing that their well-being would have been improved by better care). The lack of variance in these outcomes may reflect that variation in treatment centre characteristics does not influence psychosocial outcomes and patient views of their care. Alternatively, it may suggest that the characteristics of the four treatment centres which participated in the present study were too similar for differences in patient outcomes to be observed. PMID- 22044439 TI - The effect of black coral extraction on acute lung inflammation induced by cigarette smoke in mice. AB - Short-term exposure to cigarette smoke (CS) introduces an abundance of free radicals into the lungs, causing oxidative stress and inflammation. CS is an important risk factor related to the pathogenesis of several pulmonary diseases, especially chronic obstructive pulmonary disease. Black coral (BC) is a marine biomaterial commonly used for cigarette holders in southeast China. The purpose of the present study was to evaluate the in vivo bioactivity of BC extract (BCE). Groups of mice (male Kunming) were subjected to ultrasonic atomizing inhalation of BCE (0.3, 1.5, and 3 mg/mL) before being exposed to CS (10 cigarettes per day for 4 days). The control group and the CS group were administered normal saline rather than BCE prior to CS exposure. Superoxide dismutase (SOD), malondialdehyde (MDA), and myeloperoxidase (MPO) levels were measured in lung homogenates. Histologic and morphologic studies of the right upper lung were performed. SOD activity increased 1.32 times in the CS+BCE (3 mg/mL) group (P < .001) compared with the CS group. The MDA content increased 4% (P < .001) in the CS+BCE (3 mg/mL) group compared with the control group. MPO was reduced 40% in the CS+BCE (3 mg/mL) group compared with the CS group (P < .001). Histologic analysis revealed decreased inflammation in the BCE group compared with the CS group. These results suggest that BCE has antioxidant and anti-inflammatory activity in vivo. BCE may protect against lung injury in smokers. PMID- 22044440 TI - Disseminated fusariosis and endogenous fungal endophthalmitis in acute lymphoblastic leukemia following platelet transfusion possibly due to transfusion related immunomodulation. AB - BACKGROUND: To report a case of disseminated fusariosis with endogenous endophthalmitis in a patient with acute lymphoblastic leukemia. Transfusion associated immune modulation secondary to platelet transfusion could play an important role in the pathophysiology of this case. CASE PRESENTATION: A 9 year old male with acute lymphoblastic leukemia complicated by pancytopenia and disseminated Intravascular coagulation was given platelet transfusion. He developed disseminated fusariosis and was referred to the ophthalmology team for right endogenous endophthalmitis. The infection was controlled with aggressive systemic and intravitreal antifungals. CONCLUSION: Patients with acute lymphoblastic leukemia are predisposed to endogenous fungal endophthalmitis. Transfusion-associated immune modulation may further increase host susceptibility to such opportunistic infections. PMID- 22044441 TI - Liposomal formulation of curcumin attenuates seizures in different experimental models of epilepsy in mice. AB - Contemporary research indicates promising anticonvulsant effect of curcumin. However, its poor oral bioavailability is a major hindrance toward its pharmacological action. Thus, this study was carried out to evaluate the acute effect of liposome-entrapped curcumin on increasing current electroshock seizures (ICES) test, pentylenetetrazole (PTZ)-induced seizures, and status epilepticus in mice. Liposome-entrapped curcumin in doses 25 and 50 mg/kg demonstrated significant increase in seizure threshold current and latency to myoclonic and generalized seizures in ICES test and PTZ-induced seizures, respectively. Similarly, liposomal-entrapped curcumin also increased the latency to the onset and decreased the duration of seizures during status epilepticus in mice. To conclude, liposomal-entrapped curcumin possesses anticonvulsant activity against status epilepticus in mice. PMID- 22044442 TI - Awareness, treatment and control of hypertension among the elderly living in their home in Tunisia. AB - BACKGROUND: Hypertension is a cardiovascular disorder rapidly emerging as a major public health problem in developing countries. However, the acknowledgement of the prevalence and the significant impact of hypertension in elderly are very important for health policy. The objective of the present investigation was to evaluate the prevalence, awareness and treatment of hypertension among the elderly living in their home in Tunisia at Monastir City. We also examined the impact of socio-demographic characteristics and known risk factors for high blood pressure. METHODS: A community based sample of 598 non-institutionalized elderly (age >= 65 years), was selected using probabilistic multistage cluster sampling. RESULTS: There was a predominance of female (66%) and mean age was 72.3 +/- 7.4 years. The prevalence of hypertension was 52% (n = 311), awareness (81%, n = 252), treatment (78.4%, n = 244) and only 30.7% (n = 75) are correctly treated. The prevalence of hypertension was higher for the female population (55.5%) when compared to males (45%). No urban/rural differences were observed and no difference was observed by educational level. Multiple logistic regression analyses identified a higher body mass index, diabetes mellitus and disability as important correlates of the prevalence of hypertension. CONCLUSION: These findings provide important information on the prevalence, awareness and control of hypertension in Monastir City and confirm their association with other cardio vascular risk factors. Effective public health measures and strategies are needed to improve prevention, diagnosis and access to treatment of this elderly population. PMID- 22044443 TI - Demographic differences in estimated blood donor eligibility prevalence in the United States. AB - BACKGROUND: The prevalence of blood donor eligibility factors has a major impact on the availability of blood donors and thus the blood supply in the United States. The prevalence of these factors may differ between demographic groups and thus help explain the differences in blood donation rates. STUDY DESIGN AND METHODS: The study population (18-69 years old who were African American [AA], white, or Hispanic) was 185,073,489. Forty eligibility factors determined by US Food and Drug Administration's Code of Federal Regulations and AABB Standards for Blood Banks and Transfusion Services were used to calculate whole blood donation eligibility rates. Eligibility data were obtained from the 2007 to 2008 National Health and Nutrition Examination Survey, National Ambulatory Medical Care Survey, US Census Bureau, and Centers for Disease Control and Prevention. Eligibility rates were determined by race/ethnicity, sex, and age groups (18-39 and 40-69 years). RESULTS: In 2007 to 2008, 122 million Americans (65.9% of the study population and 41.0% of the total US population) were estimated to be eligible to donate blood in the United States. Significant differences in eligibility rates by demographic characterizers were determined (p < 0.001): AAs (36.5%), whites (46.4%), and Hispanics (40.7%); males (45.4%) and females (42.7%); individuals 18 to 39 years old (35.8%); and individuals 40 to 69 years old (32.9%). CONCLUSIONS: AAs were significantly less eligible to donate blood than whites and Hispanics. Disparities in donor eligibility exist by race/ethnicity, sex, and age groups. PMID- 22044444 TI - Current evidence on the anticancer potential of Chios mastic gum. AB - Chios mastic gum derived from the plant Pistacia lentiscus L. variation chia has been shown to exert beneficial effects on a wide range of human disorders. The most comprehensive data so far have indicated that mastic gum provides protection against gastrointestinal malfunctions and bacterial infections. Substantial evidence has also suggested that mastic gum exhibits hepatoprotective and cardioprotective, antiinflammatory/antioxidant, and antiatherogenic properties. In the last decade, an increasing number of studies further evaluated the potential antiproliferative properties of mastic gum against several types of human neoplasia. The present review aims to summarize the current data concerning the anticancer activities of mastic gum and their major constituents, highlighting also the molecular mechanisms through which they exert anticancer function. Mastic gum constituents that belong to the chemical class of triterpenoids appear to be mainly responsible for its anticancer potential. Thus, a brief discussion is dedicated to the anticancer activity of synthetic and naturally occurring triterpenoid analogues with similar chemical structure to mastic gum constituents. Taking into consideration the available data so far, Chios mastic gum could be considered as a conglomeration of effective anticancer drugs. PMID- 22044445 TI - Validity of assessing inhibitor development in haemophilia PUPs using registry data: the EUHASS project. AB - Inhibitory antibodies to exogenous FVIII/FIX are a major complication of haemophilia treatment. Up to 30% of previously untreated patients (PUPs) with severe haemophilia A develop inhibitors, most likely during the initial 50 exposure days to concentrate. In addition to classical cohort studies, a European monitoring system (EUHASS) has been set up to evaluate inhibitor development in PUPs. The present study addresses the reliability of estimating the cumulative incidence of inhibitor development in this registry. Data from the retrospective CANAL cohort study, including 288 PUPs with severe haemophilia A and complete treatment records until the 50th exposure to FVIII, were used to simulate the consequences of several cross-sectional sampling techniques on the estimated incidence of inhibitors. Both mathematical calculus and computer modelling were applied to study the effects of sample size and the introduction of a new product. For existing concentrates, both longitudinal cohort study methods and the EUHASS method yielded similar estimates of the cumulative incidence of inhibitor cases over a 5-year time period: 27.9% (95% CI: 21-36) vs. 29.4% (22 38). For a newly introduced concentrate, a reliable estimate of inhibitor incidence with the EUHASS method could only be made after 3-4 years, even in large datasets. The results from EUHASS in inhibitor incidence in PUPs are expected to be valid. After introduction of a new concentrate, the inhibitor incidence on this concentrate can only be reliably determined after an observation period of several years. PMID- 22044446 TI - Performance of installed cooking exhaust devices. AB - The performance metrics of airflow, sound, and combustion product capture efficiency (CE) were measured for a convenience sample of 15 cooking exhaust devices, as installed in residences. Results were analyzed to quantify the impact of various device- and installation-dependent parameters on CE. Measured maximum airflows were 70% or lower than values noted on product literature for 10 of the devices. Above-the-cooktop devices with flat-bottom surfaces (no capture hood)- including exhaust fan/microwave combination appliances--were found to have much lower CE at similar flow rates, compared to devices with capture hoods. For almost all exhaust devices and especially for rear-mounted downdraft exhaust and microwaves, CE was substantially higher for back compared with front burner use. Flow rate, and the extent to which the exhaust device extends over the burners that are in use, also had a large effect on CE. A flow rate of 95 liters per second (200 cubic feet per minute) was necessary, but not sufficient, to attain capture efficiency in excess of 75% for the front burners. A-weighted sound levels in kitchens exceeded 56 dB* when operating at the highest fan setting for all 14 devices evaluated for sound performance. PRACTICAL IMPLICATIONS: Natural gas cooking burners and many cooking activities emit pollutants that can reach hazardous levels in homes. Venting range hoods and other cooking exhaust fans are thought to provide adequate protection when used. This study demonstrates that airflows of installed devices are often below advertised values and that less than half of the pollutants emitted by gas cooking burners are removed during many operational conditions. For many devices, achieving capture efficiencies that approach or exceed 75% requires operation at settings that produce prohibitive noise levels. While users can improve performance by preferentially using back burners, results suggest the need for improvements in hood designs to achieve high pollutant capture efficiencies at acceptable noise levels. PMID- 22044447 TI - The substrate specificities of sunflower and soybean phospholipases D using transphosphatidylation reaction. AB - BACKGROUND: Phospholipase D (PLD) belongs to a lipolytic enzyme subclass which catalyzes the hydrolysis and transesterification of glycerophospholipids at the terminal phosphodiester bond. RESULTS: In this work, we have studied the substrate specificity of PLDs from germinating sunflower seeds and cultured soybean cells, using their capacity of transphosphatidylation. In the presence of a nucleophilic acceptor, such as [14C]ethanol, PLD catalyzes the production of phosphatidyl-[14C]-ethanol. The resulting product is easily identified since it is well separated from the other lipids by thin-layer chromatography. The main advantage of this assay is that the phospholipid used as substrate does not need to be radiolabelled and thus allow us a large choice of polar heads and fatty acids. In vitro, we observed that sunflower and soybean cell PLD show the following decreasing order of specificity: phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol; while phosphatidylserine and phosphatidylinositol are utilized much less efficiently. CONCLUSIONS: The substrate specificity is modulated by the fatty acid composition of the phosphatidylcholine used as well as by the presence of other charged phospholipids. PMID- 22044448 TI - Incidence of retinopathy of prematurity in extremely premature infants over an 18 year period. AB - BACKGROUND: To report the incidence of retinopathy of prematurity (ROP) in a subgroup of extremely premature infants admitted to an Australian tertiary centre over an 18-year period. DESIGN: Retrospective study. Royal Brisbane and Women's Hospital Neonatal Intensive Care Unit. PARTICIPANTS: Five hundred and fifty-four infants admitted between 23 and 25.6 weeks gestational age (GA). METHODS: The 18 year study was divided into three 6-year periods for analysis: period 1 (1992 1997), period 2 (1998-2003) and period 3 (2004-2009). Infants were compared based on their week of GA and by the study period in which they were born. MAIN OUTCOME MEASURES: GA, birthweight, incidence and severity of ROP. RESULTS: Three hundred seventy-three (67.3%) infants survived until ROP screening, and 351 (63.4%) survived until discharge. ROP incidence increased from 78.2% in period 1 to 86.1% in period 3. Over the entire study, 90.5% of 23-week GA infants had ROP compared with 89.7% of 24-week GA infants and 76.1% of 25-week GA infants. Mean birthweight was significantly lower in infants with any ROP (725.1 g) and ROP of at least stage 3 (720.8 g) compared with infants without ROP (806.5 g) (P < 0.0001). Twenty-three-week GA infants had more severe ROP (28.6%) than 24 weeks (18.3%) and 25 weeks GA (11.9%). CONCLUSIONS: There has been increased survival and incidence of ROP in extremely premature infants over the past 20 years. Lower birthweight and GA are both associated with higher incidence and more severe ROP. PMID- 22044449 TI - Aquagenic wrinkling of the palms and the potential role for genetic testing. AB - Aquagenic wrinkling of the palms (AWP) is a condition characterized by excessive wrinkling, palmar edema, and whitish papules accompanied by pain, pruritus, or discomfort after brief immersion of the hands in water. It is well documented to be associated with cystic fibrosis (CF), with several theories regarding the pathogenesis having been proposed. We report a case of two sisters with AWP in whom CF has not been diagnosed and review the literature on AWP and its association with CF and CF carrier status. Because diagnosis of mild forms CF or knowledge of an underlying CF genetic mutation is frequently unknown, identification of AWP may represent the only sign of such mutations. The dermatologist plays an integral role in early detection of AWP, and the importance of genetic testing in such patients cannot be overlooked. We recommend various measures to apply in clinical practice to ensure diagnosis and decrease morbidity and mortality in patients. PMID- 22044450 TI - Maternal periodontitis as a risk factor for prematurity. AB - BACKGROUND: The aim of this study was to investigate maternal periodontitis associated with prematurity. METHODS: We carried out a case-control study including 718 puerperae who experienced a spontaneous delivery: 360 cases (premature) and 358 controls (full-term). Sociodemographic, obstetric, prenatal, perinatal and periodontal data were obtained within 48 h after delivery. Periodontitis was defined as probing depth >= 4 mm and attachment loss >= 3 mm at same site, for >= 4 teeth. RESULTS: Periodontitis was associated with prematurity (odds ratio 6.95; confidence interval 3.69-13.09). Prematurity was associated with maternal age < 20 years, family income < one minimum salary, maternal schooling < 8 years, premature birth history, premature membrane rupture, ruptured membranes > 24 h, smoking, urinary tract infection, leukorrhea, pre eclampsia, prenatal consultations < 3 and precarious housing. After multivariate confounder adjustments, periodontitis remained independently associated with prematurity (odds ratio 6.05; confidence interval 3.01-12.16). CONCLUSIONS: Periodontitis is strongly associated with prematurity, indicating necessity for regular periodontal investigation and treatment during pregnancy. PMID- 22044452 TI - An analysis of the interrelationship between maternal age, body mass index and racial origin in the development of gestational diabetes mellitus. AB - OBJECTIVE: To examine the individual association between advancing maternal age, body mass index (BMI) and racial origin with the development of gestational diabetes mellitus (GDM) and the interaction between these factors. DESIGN: Retrospective study. SETTING: Fifteen maternity units in northwest London between 1988 and 2000. POPULATION: The study included 1688 women who developed GDM and 172,632 who did not. All women were nulliparous. BMI was calculated at first antenatal visit and maternal age and racial origin (White European, Black African, Black Caribbean or South Asian) were self-reported. METHODS: Binary logistic regression analysis. MAIN OUTCOME MEASURES: Development of GDM within each racial group. RESULTS: There was a strong positive association between advancing maternal age and increasing BMI, individually, and the development of GDM (P < 0.01 for both). Compared with White Europeans aged 20-24 years, the odds ratios for GDM development were significantly higher in women older than 30 years if they were White Europeans (P < 0.001), older than 25 years if they were Black Africans (P < 0.001) and older than 20 years if they were South Asians (P < 0.001). The odds ratios for GDM development were significantly higher in Black Africans and South Asians (P < 0.001 for both) irrespective of BMI, compared with White Europeans with normal BMI. CONCLUSION: Maternal age and BMI interact with racial group in relation to the prevalence of GDM. Both factors are important in the development of GDM, particularly so in Black African and South Asian women. PMID- 22044451 TI - Pre-B-cell colony-enhancing factor exerts a neuronal protection through its enzymatic activity and the reduction of mitochondrial dysfunction in in vitro ischemic models. AB - Pre-B-cell colony-enhancing factor (PBEF) is known as a rate-limiting enzyme that converts nicotinamide (NAM) to NMN in the salvage pathway of mammalian NAD+ biosynthesis. Previously we found PBEF is exclusively expressed in neurons in the mouse brain; heterozygous PBEF knockout (Pbef+/-) mice have larger ischemic lesion than wild type mice in photothrombosis-induced ischemia. For the mechanistic study of neuronal protective role of PBEF, we used in vitro oxygen glucose deprivation (OGD) and glutamate excitotoxicity models of primary cultured neurons in current study. Our results showed that the treatments of neurons with NAM and NAD+, the substrate and downstream product of PBEF, respectively, significantly reduced neuronal death after OGD and glutamate excitotoxicity, while treatment of neurons treated with FK866, a PBEF inhibitor, increased neuronal death after OGD. Furthermore, over-expression of human PBEF reduced glutamate excitotoxicity, while over-expression of human PBEF mutants (i.e. H247A and H247E) without enzymatic activity had no effect on neuronal death. We further tested the effect of PBEF on mitochondrial function and biogenesis. Our results show that addition of NAD+ and NAM increased mitochondrial biogenesis in neurons after OGD. Over-expression of PBEF in neurons reduced mitochondrial membrane potential depolarization following glutamate stimulation, while over-expression of H247A and H247E did not affect mitochondrial membrane potential depolarization. We conclude that PBEF has a neuroprotective effect in ischemia through its enzymatic activity for NAD+ production that can ameliorate mitochondrial dysfunction. PMID- 22044453 TI - Oncological outcomes of robot-assisted radical cystectomy. PMID- 22044454 TI - How Facebook almost ended my career with a single click. PMID- 22044455 TI - Strategies to reduce exposure of fumonisins from complementary foods in rural Tanzania. AB - Feeding infants with maize can expose them to fumonisin mycotoxins. We assessed fumonisin exposure from complementary foods in rural Tanzania and determined strategies to reduce the exposure. We conducted a cross-sectional study in four villages of Tarakea division, Northern Tanzania. We used a repeat 24-hour dietary recall to collect data of maize consumption as complementary food for 254 infants aged 6-8 months. Fumonisin concentrations in the maize were also estimated. Fumonisin exposure was assessed using @risk analysis software. With the software, several maximum fumonisin contamination and maize consumption patterns were combined in order to determine effective strategies for minimizing fumonisin exposure. Of the infants, 89% consumed maize at amounts up to 158g/person/day (mean; 43g/person/day+/-28). The maize was contaminated with fumonisins at levels up to 3201ugkg(-1) . Risk of fumonisin intake above the provisional maximum tolerable daily limit of 2ugkg(-1) body weight was 15% (95% confidence interval; 10-19). The risk was minimized when the maximum contamination was set at 150ugkg( 1) . The risk was also minimized when the maximum consumption was set at 20g/child/day while keeping the maximum contamination at the European Union (EU) maximum tolerated limit (MTL) of 1000ugkg(-1) . Considering the economical and technological limitations of adopting good agricultural practices in rural Tanzania, it is practically difficult to reduce contamination in maize to 150ugkg(-1) . We suggest adoption of the EU MTL of 1000ugkg(-1) for fumonisins in maize and reduction, by replacement with another cereal, of the maize component in complementary foods to a maximum intake of 20g/child/day. PMID- 22044456 TI - Porous quaternized chitosan nanoparticles containing paclitaxel nanocrystals improved therapeutic efficacy in non-small-cell lung cancer after oral administration. AB - Clinical application of paclitaxel (PTX) is limited because of its poor solubility in aqueous media. To overcome this hurdle, we devised an oral delivery system by encapsulating PTX into N-((2-hydroxy-3-trimethylammonium) propyl) chitosan chloride (HTCC) nanoparticles. These nanoparticles were small (~130 nm), had a narrow size distribution, and displayed high loading efficiency owing to the homogeneous distribution of PTX nanocrystals. The matrix hydrophilicity and porous structure of the obtained nanoparticles accelerated their degradation and improved drug release. In vitro and in vivo transport experiments had proved that the presence of positive charges enhanced the intestinal permeability of these nanoparticles. Further in vitro experiment of cytotoxicity showed that the PTX loaded HTCC nanoparticle (HTCC-NP:PTX) was more effective than native PTX owing to enhanced cellular uptake. Drug distribution in tissues and in vivo imaging studies confirmed the preferred accumulation of HTCC-NP:PTX in subcutaneous tumor tissue. Subsequent tumor xenograft assays demonstrated the promising therapeutic effect of HTCC-NP:PTX on inhibition of tumor growth and induction of apoptosis in tumor cells. Additional investigation into side effects revealed that HTCC-NP:PTX caused lower Cremophor EL-associated toxicities compared with Taxol. These results strongly supported the notion that HTCC nanoparticle (HTCC-NP) is a promising candidate as an oral carrier of PTX for cancer therapy. PMID- 22044457 TI - Thoracoscopic repair of esophageal atresia and tracheo-esophageal fistula in neonates: evolution of a technique. AB - Advancements in minimally invasive surgical techniques and instruments for neonates have allowed even the most complex neonatal procedures to be endoscopically approached. In 1999, the first successful thoracoscopic repair of an esophageal atresia (EA) was performed in a 2-month-old infant. One year later, the first totally thoracoscopic repair of an atresia with distal fistula (tracheo esophageal fistula [TEF]) was realized in a newborn. Over the ensuing 10 years, this technique was used and modified by a single surgeon in 49 consecutive patients. Overall, 43 patients with TEF and 6 with pure EA were repaired by using a thoracoscopic approach. An additional 3 patients with H-type TEF were also thoracoscopically treated. Weight ranged from 1.2 to 3.8 kg. Operative time ranged from 50 to 120 minutes. In fact, 48 out of 49 were successfully completed thoracoscopically. There were 2 patients with leaks that resolved with conservative management. Thirty percent of patients required at least one dilatation, but this number dropped to less than 10% in the second half of the series. There were no deaths and no recurrent fistula. Thoracoscopic TEF repair has proved to be an effective and safe technique. Evolution of the technique has resulted in fewer complications while avoiding the significant short- and long term morbidity associated with thoracotomy in neonates. PMID- 22044458 TI - Williams syndrome: a relationship between genetics, brain morphology and behaviour. AB - BACKGROUND: Genetically Williams syndrome (WS) promises to provide essential insight into the pathophysiology of cortical development because its ~28 deleted genes are crucial for cortical neuronal migration and maturation. Phenotypically, WS is one of the most puzzling childhood neurodevelopmental disorders affecting most intellectual deficiencies (i.e. low-moderate intelligence quotient, visuospatial deficits) yet relatively preserving what is uniquely human (i.e. language and social-emotional cognition). Therefore, WS provides a privileged setting for investigating the relationship between genes, brain and the consequent complex human behaviour. METHODS: We used in vivo anatomical magnetic resonance imaging analysing cortical surface-based morphometry, (i.e. surface area, cortical volume, cortical thickness, gyrification index) and cortical complexity, which is of particular relevance to the WS genotype-phenotype relationship in 22 children (2.27-14.6 years) to compare whole hemisphere and lobar surface-based morphometry between WS (n = 10) and gender/age matched normal controls healthy controls (n = 12). RESULTS: Compared to healthy controls, WS children had a (1) relatively preserved Cth; (2) significantly reduced SA and CV; (3) significantly increased GI mostly in the parietal lobe; and (4) decreased CC specifically in the frontal and parietal lobes. CONCLUSION: Our findings are then discussed with reference to the Rakic radial-unit hypothesis of cortical development, arguing that WS gene deletions may spare Cth yet affecting the number of founder cells/columns/radial units, hence decreasing the SA and CV. In essence, cortical brain structure in WS may be shaped by gene-dosage abnormalities. PMID- 22044459 TI - Abrogation of cisplatin-induced nephrotoxicity by emodin in rats. AB - Nephrotoxicity of the anticancer drug cisplatin (CP) involves the generation of reactive oxygen species in renal cortex, and emodin (a rhubarb anthraquinone) has strong antioxidant and anticancer actions. Therefore, we tested here the possible ameliorative effect of emodin on CP nephrotoxicity in rats. Emodin was given orally (10 mg/kg/day for nine consecutive days), and on day 4, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Five days after CP treatment, rats were killed, and blood and urine samples, and kidneys were collected for the assessment of histopathological renal damage and apoptosis, and for biochemical estimation of creatinine and urea concentrations in plasma and urine, several cytosolic antioxidant enzyme activities in kidneys, and urinalyses. CP significantly increased the concentrations of urea and creatinine, and decreased creatinine clearance. It also significantly reduced cortical glutathione concentration and the activity of superoxide dismutase. CP treatment significantly increased urine volume and N acetyl-beta-D-glucosaminidase activity and significantly decreased osmolarity and protein concentrations. Emodin treatment markedly and significantly mitigated all these effects. Sections from saline- and emodin-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with emodin. The concentration of CP in the cortical tissues was not significantly altered by emodin treatment. The results suggested that emodin had ameliorated CP nephrotoxicity in rats. Pending further pharmacological and toxicological studies emodin may be considered a potentially useful nephroprotective agent. PMID- 22044460 TI - Site directed biotinylation of filamentous phage structural proteins. AB - Filamentous bacteriophages have been used in numerous applications for the display of antibodies and random peptide libraries. Here we describe the introduction of a 13 amino acid sequence LASIFEAQKIEWR (designated BT, which is biotinylated in vivo by E. coli) into the N termini of four of the five structural proteins of the filamentous bacteriophage fd (Proteins 3, 7, 8 and 9). The in vivo and in vitro biotinylation of the various phages were compared. The production of multifunctional phages and their application as affinity reagents are demonstrated. PMID- 22044461 TI - Antibody-directed neutralization of annexin II (ANX II) inhibits neoangiogenesis and human breast tumor growth in a xenograft model. AB - Activation of the fibrinolytic pathway has long been associated with human breast cancer. Plasmin is the major end product of the fibrinolytic pathway and is critical for normal physiological functions. The mechanism by which plasmin is generated in breast cancer is not yet fully described. We previously identified annexin II (ANX II), a fibrinolytic receptor, in human breast tumor tissue samples and observed a strong positive correlation with advanced stage cancer (Sharma et al., 2006a). We further demonstrated that tissue plasminogen activator (tPA) binds to ANX II in invasive breast cancer MDA-MB231cells, which leads to plasmin generation (Sharma et al., 2010). We hypothesize that ANX II-dependent plasmin generation in breast tumor is necessary to trigger the switch to neoangiogenesis, thereby stimulating a more aggressive cancer phenotype. Our immunohistochemical studies of human breast tumor tissues provide compelling evidence of a strong positive correlation between ANX II expression and neoangiogenesis, and suggest that ANX II is a potential target to slow or inhibit breast tumor growth by inhibiting neoangiogenesis. We now report that administration of anti-ANX II antibody potently inhibits the growth of human breast tumor in a xenograft model. Inhibition of tumor growth is at least partly due to attenuation of neoangiogenic activity within the tumor. In vitro studies demonstrate that anti-ANX II antibody inhibits angiogenesis on three dimensional matrigel cultures by eliciting endothelial cell (EC) death likely due to apoptosis. Taken together, these data suggest that selective disruption of the fibrinolytic activity of ANX II may provide a novel strategy for specific inhibition of neoangiogenesis in human breast cancer. PMID- 22044462 TI - The Arosenius Fund. PMID- 22044463 TI - Mutation screening of patients with Alzheimer disease identifies APP locus duplication in a Swedish patient. AB - BACKGROUND: Missense mutations in three different genes encoding amyloid-beta precursor protein, presenilin 1 and presenilin 2 are recognized to cause familial early-onset Alzheimer disease. Also duplications of the amyloid precursor protein gene have been shown to cause the disease. At the Dept. of Geriatric Medicine, Karolinska University Hospital, Sweden, patients are referred for mutation screening for the identification of nucleotide variations and for determining copy-number of the APP locus. METHODS: We combined the method of microsatellite marker genotyping with a quantitative real-time PCR analysis to detect duplications in patients with Alzheimer disease. RESULTS: In 22 DNA samples from individuals diagnosed with clinical Alzheimer disease, we identified one patient carrying a duplication on chromosome 21 which included the APP locus. Further mapping of the chromosomal region by array-comparative genome hybridization showed that the duplication spanned a maximal region of 1.09 Mb. CONCLUSIONS: This is the first report of an APP duplication in a Swedish Alzheimer patient and describes the use of quantitative real-time PCR as a tool for determining copy number of the APP locus. PMID- 22044464 TI - Microtensile bond strength of 4 dentin adhesives to primary dentin. AB - PURPOSE: This study's purpose was to evaluate the aging effect on the bond strength of 4 adhesive systems on primary dentin 24 hours and 6 months after bonding. METHODS: The crowns of extracted, caries-free primary molars were grounded and flat surfaces were prepared and distributed into 4 groups (n=7-9). The adhesives Scotchbond Multi-purpose (SMP), Single Bond (SB), Clearfil SE Bond (CSB), and Adper Prompt L-Pop (APL) were applied with the composite resin Filtek Z-250. Specimens were stored in distilled water (37 degrees C/24h), the crowns were sectioned, and 0.8-mm2 resin-dentin sticks were obtained and divided into 2 groups: (1) 24h; and (2) 6m. Each group's specimens were tested under tensile at 0.5 mm/minute until they fractured. The fractured sticks were examined by scanning electron microscopy. The data were analyzed by 2-way repeated measures: analysis of variance; Tukey's test (P<.05); and Kruskal-Wallis test (P<.05). RESULTS: The mTBS (MPa) means values were: SMP=33.28 (2.05), SB=23.27 (4.78), APL=20.64 (10.66), and CSB=18.94 (11.94) for the 24-hour group; and SMP=30.59 (6.29), SB=22.39 (5.9), CSB=21.50 (10.67), and APL=17.19 (6.88) for the 6-month group. The most frequent fracture type found was cohesive failure of the adhesive and mixed, with no statistically significant difference found between the groups. CONCLUSIONS: Resin bond strength on primary dentin was not influenced by aging for the adhesive systems tested. PMID- 22044465 TI - Conservative approach to the treatment of keratocystic odontogenic tumor. AB - The odontogenic keratocyst, also known as the keratocystic odontogenic tumor, is an aggressive, intraosseous lesion of odontogenic origin that presents a high rate of recurrence. Treatment modalities include aggressive surgical procedures and more conservative approaches that significantly influence the lesion's recurrence potential. The purpose of this case report was to demonstrate a conservative approach in the treatment of an extensive keratocystic odontogenic tumor, located in the mandible's posterior region, using decompression and enucleation. PMID- 22044466 TI - Monitoring pediatric blood pressure at dental appointments. AB - Numerous studies have tracked blood pressure from adolescence into adulthood. It is increasingly apparent that the recent increase in obesity and resultant end organ effects of hypertension originates in childhood. Pediatric hypertension is a significant health concern that, if left untreated, can affect a child's cardiovascular, endocrine, renal, and neurologic systems. In 2004, the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recommended that bloodpressure should be monitored in pediatric patients who are at least 3-years-old and that this procedure should be a part of the health care visit in all health facilities, rather than just within the medical office. The purpose of this article was to emphasize the need for following these recommendations at oral care visits and suggest a simplified pediatric blood pressure table that dental clinicians can use to identify children who need referrals to medical facilities for evaluation of blood pressure. PMID- 22044467 TI - Prevalence of dental trauma and associated factors among 1- to 4-year-old children. AB - PURPOSE: The purpose of this study was to estimate the prevalence of dental trauma among 1- to 4-year-old children and test the association between dental trauma and demographic, socioeconomic, and clinical factors. METHODS: Five calibrated researchers (intra- and interexaminer kappa values=0.89 and 0.81, respectively) examined a representative sample of 407 children in the city of Matozinhos, Minas Gerais, Brazil, during the 2008 national vaccination campaign. Statistical analysis was performed via descriptive analysis, chi-square test (P<.05), and logistic regression. RESULTS: The prevalence of dental trauma was 47%; among the 407 children examined, 187 had suffered dental trauma. The most prevalent type of alteration due to dental trauma was enamel fracture (85%), followed by enamel-dentin fracture without pulp exposure (11%) and enamel-dentin fracture with pulp exposure (3%). The main location where the trauma occurred was at home (89%), with the cause reported by parents as accidents while running, playing, or crawling (79%). After adjusting for the variables, the child's age (P>.01) and number of siblings (P>.01) remained associated with the outcome. CONCLUSION: Results indicate the need for public health policies that include dental trauma as one of the priorities directed at young children. PMID- 22044468 TI - Distribution and severity of erosion among 5-year-old children in a city in India. AB - PURPOSE: The purpose of this descriptive, cross-sectional study was to determine the prevalence and distribution of dental erosion among 5-year-old schoolchildren in Belgaum, North Karnataka, India. METHODS: A random sample of 1,100 5-year-old schoolchildren who met the inclusion criteria were included in the study, of whom 1,002 actively participated. The questionnaire given to parents pertained to sociodemographic factors, and the parents were instructed to maintain their child's 3-day diary to assess his/her existing dietary habits. Later, the questionnaire was collected and a clinical examination for dental erosion was performed. A modified Smith and Knight index was used to assess the extent of dental erosion. The child's socioeconomic status was assessed using Kuppuswamy's classification. Statistical analysis was performed using the chi-square test, Spearman's rank correlation coefficient tests and multiple logistic regression analysis. RESULTS: The prevalence of dental erosion was approximately 29% (with a higher prevalence observed in females). CONCLUSION: A statistically significant association was found between diet type, type and time of exposure to acidic diet and dental erosion. PMID- 22044469 TI - Factors affecting early childhood caries among WIC-enrolled children in Linn County, Iowa. AB - PURPOSE: The purpose of this study was to examine the factors associated with early childhood caries (ECC) among children enrolled in 3 centers offering Iowa Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) services in Linn County, Iowa. METHODS: Data pertaining to dental caries and its determinants were collected for 115 children. Bivariate and multivariable analyses were conducted concerning outcome variables of ECC and having greater than 50 colony-forming units (CFUs) of salivary mutans streptococcus (>50 CFUs). RESULTS: The final logistic regression model for factors associated with ECC found that children with presence of visible plaque were 2.78 times more likely to have ECC (odds ratio [OR]=3.78, 95% confidence interval [CI]=1.41-10.16) and children were 0.13 times more likely to have ECC (OR=1.13, 95% CI=1.04-1.26) for each increase of one month in age. A final logistic model concerning greater than 50 CFUs showed that the children with presence of plaque on any maxillary incisor were 2.39 times more likely to have greater than 50 CFUs (OR=3.39, 95% CI=1.28 8.96) and the children were 0.61 times more likely to have greater than 50 CFUs with an increase in cariogenicity of sippy cup contents by 1 level (OR=1.61, 95% CI=1.03-2.50). CONCLUSIONS: Presence of visible plaque on maxillary incisors was associated with increased risk for presence of early childhood caries. The presence of visible plaque on any maxillary incisor and more cariogenicity of sippy cup contents were associated with having more than 50 CFUs. PMID- 22044470 TI - Longitudinal changes in parental satisfaction: mixed dentition esthetics. AB - PURPOSE: This study's purpose was to report on parents' esthetic perceptions of their children's mixed dentition and parental satisfaction changes over time. METHODS: A total of 376 parents completed esthetic questionnaires concerning satisfaction with their children's teeth at 9- and 11-years-old. Changes in esthetic perceptions were compared based on fluorosis, nonfluoride opacity status (evaluated at 9-years-old), and other factors. RESULTS: A total of 36% had definitive fluorosis on permanent maxillary incisors. Fluorosis (P=.003) and opacity (P=.02) status were significantly related to reduced likelihood of parental satisfaction at 11-years-old. Parents were less satisfied with overall tooth color at 11 vs 9-years-old (P=.045), but revealed no significant change in satisfaction with overall appearance (P=.17). Shape and color concerns increased (both P=.003), while spacing concerns decreased (P=.004). Parental satisfaction increases were associated with higher socioeconomic status (P=.03) and starting orthodontic treatment (P=.002), but changes were not significantly associated with fluorosis (P=.38) or opacities (P=.81). CONCLUSIONS: Parents were generally less satisfied with overall tooth color at 11 (vs 9) years old and had greater concerns about tooth shape and color, but fewer concerns with spacing. Improvement in parental satisfaction with overall appearance was related to higher socioeconomic status and having begun orthodontic treatment. PMID- 22044471 TI - Giant cell fibroma of the maxillary gingiva in children: a case report. AB - The purpose of this paper is to describe a giant cell fibroma in the maxillary gingiva of an 11-year-old girl. After excisional biopsy, histological examination showed the presence of numerous giant, multinucleated, stellate-shaped cells dispersed throughout the fibrous tissue of the lamina propria. No recurrence was observed after the 1-year follow-up. Since this lesion is clinically similar to other non-neoplastic lesions and very uncommon in children, establishing a correct diagnosis can be difficult and achieved only based on specific histological characteristics. Thus, it is important that pediatric dentists have knowledge about this uncommon lesion. PMID- 22044472 TI - Allergic contact dermatitis associated with the use of facemask on a patient with a history of atopy. AB - Allergic contact dermatitis (ACD) is a skin inflammation caused by an allergic reaction after contact with small external substances capable of being absorbed by the skin. There are several studies describing allergic reactions to intraoral orthodontic appliances, especially those containing nickel. Allergic reactions due to extraoral appliances are not as frequent, and there are relatively few studies about them. Extraoral eactions are attributed to metallic, elastic, or textile parts of the extraoral appliances. This article's purpose was to report the appearance of an allergic contact dermatitis reaction in a 9-year, 2-month old female patient, with a history of atopic dermatitis, after an orthodontic facemask was fitted. Rapid maxillary expansion was also performed with a Hyrax appliance while a facemask was used. Early diagnosis of this pathology is essential in order to achieve a total regression of the reaction. Orthodontists should be aware that ACD can be caused by facemasks in predisposed patients. PMID- 22044473 TI - Complex odontoma: report of a five-year follow-up case. AB - Odontomas are odontogenic tumors that usually present as benign lesions. They are easily diagnosed and affect individuals in their first and second decades of life. In most cases, odontomas are asymptomatic and the presence could be suspected due to the delay in tooth eruption or via routine radiographic examinations. Treatment of choice has been surgical removal of the lesion, and prognosis is usually favorable because of its benign characteristics and rare recurrence. The purpose of this study is to report the case of a complex odontoma in a child impacting a permanent molar and preventing its eruption. The lesion was surgically removed, and the eruption of the permanent mandibular left second molar tooth occurred after 5 months. Clinical, radiographic, and histopathological characteristics were studied in this case. PMID- 22044475 TI - Neural intrinsic connectivity networks associated with risk aversion in old age. AB - Risk aversion is associated with several important real world outcomes. Although the neurobiological correlates of risk aversion have been studied in young persons, little is known of the neurobiological correlates of risk aversion among older persons. Resting-state functional MRI data were collected on 134 non demented participants of the Rush Memory and Aging Project, a community-based cohort study of aging. Risk aversion was measured using a series of standard questions in which participants were asked to choose between a certain monetary payment ($15) versus a gamble in which they could gain more than $15 or gain nothing, with potential gains varied across questions. Participants determined to be "high" (n=27) and "low" (n=27) in risk aversion were grouped accordingly. Using a spherical seed region of interest in the anterior cingulate cortex, voxel wise functional connectivity network similarities were observed in bilateral frontal, anterior and posterior cingulate, insula, basal ganglia, temporal, parietal, and thalamic regions. Differences in functional connectivity were observed such that those low in risk aversion had greater connectivity to clusters in the superior, middle, and medial frontal regions, as well as cerebellar, parietal, occipital, and inferior temporal regions. Those high in risk aversion had greater connectivity to clusters in the inferior and orbital frontal, parahippocampal, and insula regions, as well as thalamic, parietal, precentral gyrus, postcentral gyrus, and middle temporal regions. Similarities and differences in functional connectivity patterns may reflect the historical recruitment of specific brain regions as a network in the active processing of risk in older adults. PMID- 22044476 TI - Head and eye movements in rats with pontine reticular lesions in comparison with primates: a scientific memoir and a fresh look at some old and 'new' data. AB - The author recounts the process of discovery in Philip Teitelbaum's laboratory, which began with the observation of vestibular head stabilization in a rat with brainstem lesions, of the essential roles of the pontine reticular formation (PRF) in the rat in ipsiversive head as well as eye movements. The PRF in the rat appears to be in the pathways for most direction-changing movements of the eyes and head, leaving vestibular and optokinetic stabilizing movements intact and uninterrupted. The author postulates that a response to the sliding of feet or paws, or a "substrate-kinetic reflex," works together with vestibular and optokinetic reactions to stabilize an animal's directions of gaze and locomotion on the ground. Previously unpublished data are presented from later observations and recordings of rats with kainic acid lesions in the PRF, which support the conclusion that neurons in the PRF are essential for head as well as eye movements in the rat. In contrast, Volker Henn observed no obvious loss of head movements in monkeys that had a loss of fast eye movements from kainic acid lesions of the PRF. The author and others observed that quick phases of head nystagmus develop some time after quick phases of ocular nystagmus in normal human infants; in other words, after the PRF is functioning for eye movements. The author concludes that in primates, the pathway for head movements through the PRF has been replaced by a newer pathway, leaving certain PRF regions to be devoted to mediating only eye movements. PMID- 22044477 TI - Volumetric changes of the graft after maxillary sinus floor augmentation with Bio Oss and autogenous bone in different ratios: a radiographic study in minipigs. AB - OBJECTIVE: The objective of the present study was to learn about the volumetric changes of the graft after maxillary sinus floor augmentation with Bio-Oss and autogenous bone from the iliac crest or the mandible in different ratios in minipigs. MATERIAL AND METHODS: Bilateral maxillary sinus floor augmentation was performed in 40 minipigs with: (A) 100% autogenous bone, (B) 75% autogenous bone and 25% Bio-Oss, (C) 50% autogenous bone and 50% Bio-Oss, (D) 25% autogenous bone and 75% Bio-Oss, and (E) 100% Bio-Oss. The autogenous bone graft was harvested from the iliac crest or the mandible and the graft composition was selected at random and placed concomitant with implant placement. Computed tomographies of the maxillary sinuses were obtained preoperatively, immediately postoperatively, and at euthanasia after 12 weeks. The volumetric changes of the graft were estimated using the Cavalieri principle and expressed as mean percentage with a 95% confidence interval (CI). RESULTS: The mean volume of the graft was reduced by (A) 65% (95% CI: 60-70%), (B) 38% (95% CI: 35-41%), (C) 23% (95% CI: 21-25%), (D) 16% (95% CI: 12-21%), and (E) 6% (95% CI: 4-8%). The volumetric reduction was significantly influenced by the ratio of Bio-Oss and autogenous bone (P<0.001), but not by the origin of the autogenous bone graft (P=0.2). CONCLUSIONS: The volume of autogenous bone grafts from the iliac crest and the mandible is reduced significantly after maxillary sinus floor augmentation in minipigs. The graft volume is better preserved after the addition of Bio-Oss and the volumetric reduction is significantly influenced by the ratio of Bio-Oss and autogenous bone. However, further studies are needed addressing the amount of new bone formation and bone-to-implant contact before the final conclusion can be made about the optimal ratio of Bio-Oss and autogenous bone. PMID- 22044478 TI - Molecular characterization of goose- and chicken-type lysozymes in emu (Dromaius novaehollandiae): evidence for extremely low lysozyme levels in emu egg white. AB - Lysozyme (LZ), a bacteriolytic enzyme, is found in the egg white of many avian eggs and plays an important role in host defense; however, LZ activity in emu (Dromaius novaehollandiae) egg white is exceptionally undetectable. We cloned and characterized emu goose-type LZ (LZG) and chicken-type LZ (LZC) genes. RT-PCR analysis revealed very low LZG gene expression levels and absence of LZC gene expression in the emu oviduct. Sequencing of full-length LZG and LZC cDNAs indicated that their amino acid sequences show high similarities to ostrich LZG and LZC, respectively, with conserved catalytic residues for enzymatic activities. Whereas recombinant emu LZG prepared using Pichia pastoris exhibited similar enzyme activity as ostrich LZG, recombinant emu LZC exhibited significantly higher lytic activity than chicken LZC. We concluded that emus have functional genes for both LZG and LZC like many other avians, and the LZG gene is expressed in oviduct probably as in other ratite, however, its expression levels in egg white were low to be detected. PMID- 22044479 TI - Fluctuations in relative humidity provided to extremely low-birthweight infants (R1). AB - BACKGROUND: In extremely low-birthweight infants, the addition of relative humidity (RH) improves thermal stability, fluid and electrolyte balance. However, during routine care this microenvironment is frequently disturbed. The objective of this study was to determine the frequency, magnitude and direction of fluctuations in RH provided to extremely low-birthweight infants. METHODS: All infants in our study had ambient temperature and RH continuously recorded for 48 h using a datalogger device (RH32S-C2). A clinically acceptable range for RH was defined as the set point +/- 10%. A secondary analysis was performed to compare outcomes between infants that spent > 50% of the time out-of-range (OOR) or inside the range (IR). A P-value < 0.05 was significant. RESULTS: A total of 20 infants were included. Important fluctuations were detected by the device with infants spending 40% and 14% of the time above and below the range, respectively. However, the RH set point did not differ from the mean levels measured over 48 h by the RH32S-C2 or the incubator. Infants in the OOR group spent significantly more time at values higher than the planned range when compared to IR infants. CONCLUSION: Although significant fluctuations in RH above the desired range were detected in more than half of the infants, the average values were similar to the set points. Nevertheless, knowledge of these dynamic changes may help to optimize individualized care. PMID- 22044480 TI - Assessment of right ventricular endocardial dysfunction in mild-to-moderate mitral stenosis patients using velocity vector imaging. AB - PURPOSE: Right ventricular (RV) function plays an important role in the development of clinical symptoms, exercise capacity, prognosis, and survival in patients with mitral stenosis (MS). The purpose of this study was to evaluate global and regional RV systolic functions using a novel technique, VVI, in mild to-moderate MS patients without clinical symptoms of heart failure. METHODS: The study population consisted of 60 patients (mean age 51.7 +/- 11.6 years; 85% female) with isolated rheumatic mitral valve stenosis and 40 age- and sex-matched control subjects (mean age 49.1 +/- 10.5 years; 76.7% female). Conventional echocardiography, tissue Doppler imaging (TDI), strain (S), and strain rate (SRs) analysis were performed in all patients. RESULTS: Transmitral mean pressure gradient was 6.1 +/- 3.0 mmHg and mean mitral valve area was 1.41 +/- 0.31 cm(2) in patients with MS. TDI systolic velocity was significantly lower in MS patients compared to control subjects (0.13 +/- 0.03 m/sec vs. 0.17 +/- 0.03 m/sec; P < 0.0001). RV-isovolumic acceleration was reduced in MS patients (3.75 +/- 1.09 m/sec(2) vs. 4.62 +/- 1.0 m/sec(2) ; P = 0.006). RV-myocardial performance index was significantly increased in patients with MS (0.75 +/- 0.05 in MS and 0.29 +/- 0.04 in controls; P < 0.0001) revealing impaired RV systolic and diastolic function. The mean longitudinal peak systolic S and SR were significantly reduced in patients with MS (P < 0.0001). CONCLUSION: Our data revealed that RV systolic performance is reduced in patients with mild-to-moderate MS. PMID- 22044481 TI - Incidence of diabetic retinopathy in indigenous Australians within Central Australia: the Central Australian Ocular Health Study. AB - BACKGROUND: To estimate the incidence of diabetic retinopathy (DR) within the indigenous Australian population living in Central Australia. DESIGN: Clinic based cohort study. PARTICIPANTS: One thousand eight hundred eighty-four individuals aged >=20 years living in one of 30 remote communities within the statistical local area of 'Central Australia'. METHODS: Among those with diabetes mellitus (DM) (n = 1040), 432 (42%) were reviewed between 6 months and 3 years (median 21 months) after the initial examination. DR in participants with DM was graded using the Early Treatment of Diabetic Retinopathy Study classification. Baseline results were compared with those at follow-up. MAIN OUTCOME MEASURES: The incidence of any DR and vision-threatening DR (clinically significant macular oedema and/or proliferative DR) in at least one eye. RESULTS: Of those with DM but without DR at baseline, 8.41% (9.42% of those aged 40 years or older) per year developed DR. Meanwhile, 0.7% (0.92% for those aged >=40 years) of those with no DR at baseline developed vision-threatening DR per year, increasing to 8.4% per year for those with minimal or mild non-proliferative DR, and 28.2% per year for those with moderate or severe non-proliferative DR at baseline. CONCLUSION: Our study has estimated the annual incidence rates of DR among indigenous Australians living within Central Australia. These rates are similar to those from the non-indigenous population, and highlight the need for good surveillance and service provision in a population where the prevalence of diabetes is very high and the logistics of screening are complex. PMID- 22044482 TI - Improvement of cognitive function in Alzheimer's disease model mice by genetic and pharmacological inhibition of the EP(4) receptor. AB - Amyloid-beta peptide (Abeta), which is generated by the beta- and gamma-secretase mediated proteolysis of beta-amyloid precursor protein (APP), plays an important role in the pathogenesis of Alzheimer's disease (AD). We recently reported that prostaglandin E(2) (PGE(2) ) stimulates the production of Abeta through both EP(2) and EP(4) receptors and that activation of the EP(4) receptor stimulates Abeta production through endocytosis and activation of gamma-secretase. We here found that transgenic mice expressing mutant APP (APP23) mice showed a greater or lesser apparent cognitive deficit when they were crossed with mice lacking EP(2) or EP(4) receptors, respectively. Mice lacking the EP(4) receptor also displayed lower levels of Abeta plaque deposition and less neuronal and synaptic loss than control mice. Oral administration of a specific EP(4) receptor antagonist, AE3 208 to APP23 mice, improved their cognitive performance, as well as decreasing brain levels of Abeta and suppressing endocytosis and activation of gamma secretase. Taken together, these results suggest that inhibition of the EP(4) receptor improves the cognitive function of APP23 mice by suppressing Abeta production and reducing neuronal and synaptic loss. We therefore propose that EP(4) receptor antagonists, such as AE3-208, could be therapeutically beneficial for the prevention and treatment of AD. PMID- 22044483 TI - Identification and analysis of functionally important amino acids in human purinergic 12 receptor using a Saccharomyces cerevisiae expression system. AB - The purinergic 12 receptor (P2Y12) is a major drug target for anticoagulant therapies, but little is known about the regions involved in ligand binding and activation of this receptor. We generated four randomized P2Y12 libraries and investigated their ligand binding characteristics. P2Y12 was expressed in a Saccharomyces cerevisiae model system. Four libraries were generated with randomized amino acids at positions 181, 256, 265 and 280. Mutant variants were screened for functional activity in yeast using the natural P2Y12 ligand ADP. Activation results were investigated using quantitative structure-activity relationship (QSAR) models and ligand-receptor docking. We screened four positions in P2Y12 for functional activity by substitution with amino acids with diverse physiochemical properties. This analysis revealed that positions E181, R256 and R265 alter the functional activity of P2Y12 in a specific manner. QSAR models for E181 and R256 mutant libraries strongly supported the experimental data. All substitutions of amino acid K280 were completely inactive, highlighting the crucial role of this residue in P2Y12 function. Ligand-receptor docking revealed that K280 is likely to be a key element in the ligand-binding pocket of P2Y12. The results of this study demonstrate that positions 181, 256, 265 and 280 of P2Y12 are important for the functional integrity of the receptor. Moreover, K280 appears to be a crucial feature of the P2Y12 ligand-binding pocket. These results are important for rational design of novel antiplatelet agents. PMID- 22044484 TI - Aging-associated B7-DC+ B cells enhance anti-tumor immunity via Th1 and Th17 induction. AB - Because most patients with cancer are aged and because immunological functions are altered during aging, it is important to account for aging-associated immunological alterations in the design of new cancer immunotherapies. We thus compared immune populations in young and aged mice and found that B7-DC(+) (PD L2/CD273) B cells, a minor population in young mice, were significantly increased in aged mice. Induction of both Th1 and Th17 cells was significantly augmented by B7-DC(+) B cells from aged mice, and this effect was blocked with anti-B7-DC antibodies in vitro and in vivo. Moreover, retardation of tumor growth in aged mice was largely B7-DC dependent. Tumor growth in young mice was significantly inhibited by immunization with B7-DC(+) B cells from aged mice owing to increased induction of tumor antigen-specific cytotoxic T lymphocytes. These data indicate that B7-DC(+) B cells could play an important role in aging-associated cancer immunopathology as well as in other aging-associated diseases and further suggest that B7-DC(+) B cells have potential for future cancer immunotherapy. PMID- 22044485 TI - Prostate cancer active surveillance and health-related quality of life: results of the Finnish arm of the prospective trial. AB - Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance is a management option in patients with localized prostate cancer. One concern is the possible psychological burden and quality-of-life effects caused by consciousness of living with untreated cancer. Previous studies have reported controversial results about the impact of active surveillance on patient's health-related quality of life. The data of the present study support the idea that patients with low-risk prostate cancer manage well on active surveillance and do not develop short-term mental or physical quality-of-life sequelae. OBJECTIVE: To analyse longitudinal changes in general, mental and physical health-related quality of life (HRQL) and urinary and erectile function in patients with low risk prostate cancer (PC) on active surveillance (AS). PATIENTS AND METHODS: Patients comprised those (n= 124) enrolled in the Finnish arm of the Prostate Cancer Research International: Active Surveillance (PRIAS) study who were followed for at least 1 year (n= 80). All patients with PC received validated questionnaires at the start of surveillance and after 1 year of follow-up. General HRQL was assessed with the RAND 36-Item Health Survey (RAND-36), erectile function with the International Index of Erectile Function-5 (IIEF-5), and urinary symptoms with the International Prostate Symptom Score (IPSS) questionnaires. Results were also compared with an age-stratified general Finnish male population. A paired t-test served to compare results over time and a non paired t-test or a corresponding non-parametric test, when applicable, served to compare the study group with the general population. Pearson and Spearman correlations were analysed between possible HRQL-affecting factors (demographic and clinical data) and HRQL data, followed by linear regression analysis to further evaluate any possible associations. RESULTS: Of the 124 patients, 105 (85%) returned the baseline RAND-36 questionnaire, and 75 (94%) of the 80 patients answered both the baseline and follow-up questionnaires; 15 patients (12%) had discontinued AS, all for protocol-based reasons, none due to anxiety or distress. No differences existed in the HRQL main categories at the 1-year follow up (mental and physical: P= 0.142 and P= 0.154, respectively). When all the eight dimensions were analysed separately, the physical role showed statistically significant improvement from a mean of 81 to a mean of 89 (P= 0.010). No clinically significant correlations appeared between HRQL and age, diagnostic prostate-specific antigen (PSA), free PSA or PSA change during follow-up at any of the time points; in regression analysis, HRQL was not predictable by any of the variables available at diagnosis or during follow-up. No statistically significant changes occurred in urinary function as analysed by the IPSS (P= 0.121) or in erectile function by the IIEF-5 questionnaire (P= 0.583). Compared with an age-stratified Finnish general male population, patients with PC on AS had a significantly better general mental and physical HRQL at diagnosis and after 1 year of follow-up (P < 0.05). CONCLUSIONS: Active surveillance does not provoke short-term quality-of-life disturbances as assessed by standardized RAND 36, IIEF-5 and IPSS questionnaires. None of the patients changed treatment due to anxiety. Unexpectedly, PC patients on AS had significantly better general mental and physical HRQL than did a general age-stratified Finnish male population. PMID- 22044486 TI - Involving relatives in relapse prevention for bipolar disorder: a multi perspective qualitative study of value and barriers. AB - BACKGROUND: Managing early warning signs is an effective approach to preventing relapse in bipolar disorder. Involving relatives in relapse prevention has been shown to maximize the effectiveness of this approach. However, family-focused intervention research has typically used expert therapists, who are rarely available within routine clinical services. It remains unknown what issues exist when involving relatives in relapse prevention planning delivered by community mental health case managers. This study explored the value and barriers of involving relatives in relapse prevention from the perspectives of service users, relatives and care-coordinators. METHODS: Qualitative interview study nested within a randomized controlled trial of relapse prevention for individuals with bipolar disorder. The purposive sample of 52 participants comprised service users (n = 21), care coordinators (n = 21) and relatives (n = 10). Data were analyzed using a grounded theory approach. RESULTS: All parties identified benefits of involving relatives in relapse prevention: improved understanding of bipolar disorder; relatives gaining a role in illness management; and improved relationships between each party. Nevertheless, relatives were often discouraged from becoming involved. Some staff perceived involving relatives increased the complexity of their own role and workload, and some service users valued the exclusivity of their relationship with their care-coordinator and prioritized taking individual responsibility for their illness over the benefits of involving their relatives. Barriers were heightened when family relationships were poor. CONCLUSIONS: Whilst involving relatives in relapse prevention has perceived value, it can increase the complexity of managing bipolar disorder for each party. In order to fully realize the benefits of involving relatives in relapse prevention, additional training and support for community care coordinators is needed. TRIAL REGISTRATION: ISRCTN41352631 PMID- 22044487 TI - Nucleation and growth of nanoparticles in the atmosphere. PMID- 22044488 TI - How Facebook saved our day! AB - Facebook and social media networking applications use is ubiquitous across all ages and cultures. Facebook has finally begun to appear in the medical-scientific press. Today's medical literature is focused on concerns of professionalism in young health care practitioners vis-a-vis the lay public as they continuously expose themselves through this online social medium. With over 500 million users, Facebook hosts many of our patients, who are also exposed to the Internet and social media. Nobody so far has considered the opposite issue: that of physician invasion of privacy by "looking-up" a patient on Facebook during clinical practice for purposes of history-taking or diagnostic clues in situations where patients are too ill to provide needed information. We need to consider the ethical implications of privacy invasion in the current era of information technology. We need to acquire and maintain a certain level of "social media competency" to better debate the issues around Facebook and how we integrate on line content with our patients' histories of present illness (HPI) or past medical histories (if at all). PMID- 22044489 TI - Concordance of sibling's recall of measures of childhood socioeconomic position. AB - BACKGROUND: Studies of socioeconomic determinants of health often rely on recalled information on childhood socioeconomic position, despite limited evidence of the validity of this information. This study examined concordance between siblings of recalled measures of childhood socioeconomic position. METHODS: This cross-sectional study examined reports by 1280 adult sibling pairs in the National Survey of Midlife Development in the United States of seven measures of childhood socioeconomic position: father's occupation (in 9 categories), father having a professional occupation, father being a supervisor at work, father's education level, mother's education level, receipt of welfare payments, and subjective appraisal of being better or worse off financially than others. RESULTS: Concordance was high for father's professional occupation (0.97; 95% confidence interval (CI) 0.96, 0.98), father's occupation in 9 categories (0.76; 95% CI 0.73, 0.80), and receipt of welfare payments (0.95; 95% CI 0.93, 0.97). Concordance was lower for father's and mother's education level, and lowest for subjective appraisal of socioeconomic position (0.60; 95% CI 0.57, 0.64). Concordance of parental education was lower for sibling pairs with high school educations or less. CONCLUSION: Concordance of recalled measures of childhood socioeconomic position by siblings is generally but not uniformly high. PMID- 22044490 TI - Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma. AB - BACKGROUND: Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC) and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR) occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4) in the world; this study investigated effects of HCV genotype-4 (HCV-4) on prevalence of insulin resistance in chronic hepatitis C (CHC) and HCC in Egyptian patients. METHODS: Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples. RESULTS: HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23). Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p < 0.001). CONCLUSIONS: IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development. PMID- 22044491 TI - Experiences of mental health services by people with intellectual disabilities from different ethnic groups: a Delphi consultation. AB - BACKGROUND: Patient experience of those accessing mental health services has been found to be different between ethnic groups. Although the needs of people with intellectual disabilities (ID) from different ethnic communities are being increasingly recognised, little has been published about their experiences of mental health services. The aim of this study was to establish whether there are any differences in the experiences of people with ID and mental health problems from two ethnic communities in South London. METHOD: A two-round Delphi process was utilised. White British and Black or Black British service users from a specialist community-based mental health service for adults with ID completed a specially compiled questionnaire. Statements on participants' experiences, including satisfaction with care, staff members' attitudes, cultural awareness and level of support, were rated using a Likert scale. RESULTS: Twenty-four out of 32 participants (75%) completed both rounds of the Delphi consultation. Consensus (>=80% agreement with the group median) was reached for 20 items in the White group and five items in the Black group. All responses that reached consensus were positive about the services that were being received. The Black group were less positive about a range of their experiences, including the use of medication. CONCLUSIONS: People with ID from two ethnic groups were able to successfully complete a Delphi consultation regarding their experiences of mental health services. Broad consensus on positive experiences of services was reached in the White group but not for the Black participants. PMID- 22044492 TI - Accidental gallbladder perforation during laparoscopic cholecystectomy: does it have an effect on the clinical outcomes? AB - BACKGROUND: Accidental gallbladder perforation during laparoscopic cholecystectomy (LC) is on the rise because of increased attempts at minimally invasive surgery. There have been a number of studies attempting to determine the influence of gallbladder perforation on the clinical outcomes, but the results are still conflicting. Therefore, we investigated the clinical outcomes and the risk factors in patients who sustained a gallbladder perforation during LC. METHODS: We evaluated 198 patients who underwent LC between April 2009 and March 2010. Data were collected from a prospectively maintained database. RESULTS: Thirty-three patients sustained a gallbladder perforation (16.7%) and it primarily occurred during dissection of the hepatic fossa in 21 patients (63.6%). The mean operative time and duration of postoperative hospitalization were longer in the perforated group (P=.015 and P=.001). Visual analog scale scores on the first and second postoperative days were higher in the perforated group (P=.009 and P=.034). Complications such as ileus and trocar site infection developed more frequently in patients with a gallbladder perforation (P=.001 and P=.004). There was no significant factor related to gallbladder perforation except for male gender (P=.017). CONCLUSION: Accidental gallbladder perforation can cause more postoperative pain, ileus, and trocar site infection, which consequently increases the total duration of hospitalization, undermining the advantages of LC. Based on these interesting results, surgeons should make every effort to prevent gallbladder perforation by performing meticulous dissection during the operation. PMID- 22044493 TI - IVF/ICSI outcomes after culture of human embryos at low oxygen tension: a meta analysis. AB - BACKGROUND: Improved pregnancy, implantation, and birth rates have been reported after the use of reduced O2 concentration during embryo culture, mainly due to a reduction of the cumulative detrimental effects of reactive oxygen species. However, some studies have failed to report any positive effects. The objective of this meta-analysis was to evaluate the effect of a low-O2 environment on IVF/intracytoplasmic sperm injection (ICSI) outcomes. METHODS: All available published and ongoing randomised trials that compared the effects of low (~5%; OC~5) and atmospheric (~20%; OC~20) oxygen concentrations on IVF/ICSI outcomes were included. Search strategies included online surveys of databases from 1980 to 2011. The outcomes measured were fertilisation rate, implantation rate and ongoing pregnancy rates. The fixed effects model was used to calculate the odds ratio. RESULTS: Seven studies were included in this analysis. The pooled fertilisation rate did not differ significantly (P=0.54) between the group of oocytes cultured at low O2 tension and the group at atmospheric O2 tension. Concerning all cycles, the implantation (P=0.06) and ongoing pregnancy (P=0.051) rates were not significantly different between the group receiving transferred sets containing only OC~5 embryos and the group receiving transferred sets with only OC~20 embryos. In a meta-analysis performed for only those trials in which embryos were transferred on day 2/3, implantation (P=0.63) and ongoing pregnancy (P=0.19) rates were not significantly different between the groups. In contrast, when a meta-analysis was performed using only trials in which embryos were transferred on days 5 and 6 (at the blastocyst stage), the group with transferred sets of only OC~5 embryos showed a statistically significantly higher implantation rate (P=0.006) than the group receiving transferred sets with only OC~20 embryos, although the ongoing pregnancy (P=0.19) rates were not significantly different between the groups. CONCLUSIONS: Despite some promising results, it seems too early to conclude that low O2 culture has an effect on IVF outcome. Additional randomised controlled trials are necessary before evidence based recommendations can be provided. It should be emphasised that the present meta-analysis does not provide any evidence that low oxygen concentration is unnecessary. PMID- 22044494 TI - Factor V and FVIII deficiency in a young Czech woman. PMID- 22044495 TI - Immune response to Haemophilus influenzae type b conjugate vaccine in preterm infants. AB - BACKGROUND: Haemophilus influenzae type b (Hib) vaccine became available for use in Japan in December 2008. The aim of the present study was to evaluate the immunogenicity of Hib vaccine in Japanese preterm infants. METHODS: Serum samples were obtained from 54 preterm infants before the first vaccination and 1 month after the third. Anti-polyribosylribitol phosphate (PRP) antibodies were measured using an enzyme-linked immunosorbent assay method. Antibody positivity was defined as levels >1 ug/mL. RESULTS: Of the 54 preterm infants, 46 (85.2%) achieved antibody levels >1 ug/mL. This compares with the 92.4% reported in full term infants. The antibody seroconversion rate of infants starting vaccination at 2 months of age was close to being significantly lower than when vaccination was started at 3 months of age (P= 0.060). In addition, the percentage of infants achieving a positive response in the group with a history of antenatal steroid exposure was significantly higher than in those not exposed (P= 0.046). Thus, risk factors for lower Hib antibody concentrations after three doses of vaccine were age at first vaccination and lack of use of antenatal steroids. CONCLUSIONS: There is a possibility that perinatal factors and the environment unique to preterm infants are related to their lower antibody positivity rates compared to full-term infants. It may therefore be preferable to modify the proposed immunization schedule. PMID- 22044496 TI - Targeting the aldosterone pathway in cardiovascular disease. AB - Accumulated evidence has demonstrated that aldosterone is a key player in the pathogenesis of cardiovascular (CV) disease. Multiple clinical trials have documented that intervention in the aldosterone pathway can reduce blood pressure and lower albuminuria and improve outcome in patients with heart failure or myocardial infarction. Recent studies have unraveled details about the role of aldosterone at the cellular level in CV disease. The relative importance of glucocorticoids and aldosterone in terms of mineralocorticoid receptor activation is currently being debated. Also, studies are addressing which aldosterone modulator to use, which timing of treatment to aim for, and in which population to intervene. This review provides an overview of recent developments in the understanding of the role of aldosterone in CV disease, with particular reference to mechanisms and potential targets of intervention. Finally, ongoing or desirable clinical trials in the field are highlighted. The review is partly based on discussions between basic scientists and clinical trialists at the Cardiovascular Clinical Trials Forum 2009 and subsequently updated to encompass the most recent developments. PMID- 22044497 TI - Immunohistological analysis of extracted anterior cruciate ligament graft impinged against posterior cruciate ligament. AB - A young female athlete suffered from the residual instability of the knee after anterior cruciate ligament (ACL) reconstruction with hamstring autograft. The 3 dimensional (3-D) CT scan showed the "high noon" positioning of the primary femoral bone tunnel. The revision surgery with anatomic double-bundle technique was performed two years after the primary surgery and the femoral tunnels were created with the assistance of the 3-D fluoroscopy-based navigation. An arthroscopic examination confirmed the ACL graft impingement against posterior cruciate ligament (PCL) when the knee was deeply flexed. The histological analysis of the resected primary ACL graft showed local inflammatory infiltration, enhanced synovial coverage and vascularization at the impinged site. The enhanced expression of vascular endothelial growth factor (VEGF) at the impinged area when compared with non-impinged area was observed on immunohistochemical analysis. Abnormal mechanical stress by the impingement against PCL might have induced chronic inflammation and VEGF overexpression. PMID- 22044498 TI - Assessment of mitral annulus (p3 segment) asymmetric deformity in myocardial infarction with ischemic regurgitation by real time three-dimensional echocardiography. AB - OBJECTIVE: The three-dimensional (3D) saddle shape of the mitral annulus (MA) is well characterized in humans, but segmental MA deformity and regurgitation suffered after the ischemic damage of myocardial infarction (MI) is poorly understood. In this study, such changes were assessed in patients with ischemic mitral regurgitation (IMR) post-MI, using our computerized 3D echo technique. METHODS: A patient cohort (n = 72) with IMR due to inferior or anterior MI and normal controls (n = 20) were enrolled for 3D MA echo studies. Sequential coordinates of MA were manually measured from each of 18 radial planes, cropped in midsystole, to generate 3D MA images. In addition, six segmental (A1, A2, A3, P1, P2, P3) parameters of MA and global features, such as circumference, area, and height, were calculated. RESULTS: All six segments of MA were significantly dilated in the IMR group compared with corresponding segments of normal controls. Although there were no significant intragroup differences in A1, A2, and A3 segments, a greater degree of P3 segmental MA deformity was observed only in patients following inferior MI. CONCLUSION: The MA dilatation observed in patients with IMR after MI was more pronounced in patients with anterior versus inferior MI. However, P3 segmental dilatation of MA was significantly greater in patients after inferior IM with significant IMR, corresponding with more severe asymmetric MA deformity. (Echocardiography 2012;29:42-50). PMID- 22044499 TI - Livedoid vasculopathy associated with sickle cell trait: significant improvement on aspirin treatment. AB - Livedoid vasculopathy (LV) is a chronic, recurrent, painful cutaneous disease manifesting as longstanding distal lower extremity ulcers that scar leaving stellate atrophic lesions known as 'atrophie blanche'. A significant number of cases have been associated with thrombophilic abnormalities. In this study, we describe, to the best of our knowledge, the first report of LV only associated with sickle cell trait with significant improvement on aspirin. PMID- 22044500 TI - Stimulation of pulmonary immune responses by the TLR2/6 agonist MALP-2 and effect on melanoma metastasis to the lung. AB - Given that metastasized melanoma is a fatal disease in most cases, it is tempting to develop strategies to a priori prevent metastasis. We have stimulated the pulmonary innate immune system by macrophage-activating lipopeptide-2 (MALP-2), a specific agonist at Toll-like receptor (TLR) 2/6, and investigated its impact on experimental melanoma metastasis. In C57BL/6 mice, intratracheal application of MALP-2 induced a profound influx of neutrophils and macrophages into the lung, which peaked after 24 h (sixfold increase) and returned to baseline within 72 h. Further analysis revealed that MALP-2 also markedly induced VCAM-1 expression on pulmonary blood vessels. In vitro experiments demonstrated that this adhesion molecule mediates binding of B16F10 melanoma cells. Furthermore, in vivo or in vitro treatment with MALP-2 did not significantly affect the ability of immune cells to lyse melanoma cells. As a consequence, notwithstanding the profound pulmonary immune response induction and in contrast to conclusions drawn from some previous publications, the net extent of experimental metastasis did not change significantly, regardless of the application regimen of MALP-2 prior to, concomitant with or after tumor cell inoculation. Melanoma cells stably transfected with green fluorescent protein allowed tracking of early events after tumor cell dissemination and showed that MALP-2-mediated TLR2/6 activation did not interfere with pulmonary melanoma cell arrest. Likewise, boosting the immune induction after establishment of metastases did not change the clinical outcome. These unexpected results vividly counsel caution regarding predictions of immunomodulating therapies, as multiple intertwined effects may influence the net outcome. PMID- 22044501 TI - Type of transrectal ultrasonography probe influences prostate cancer detection rates on repeat prostate biopsy. AB - It is known that the end-fire probe detects more prostate cancer on initial prostate biopsy, but there is no literature looking at the influence of type of probe on repeat biopsy. Given that the literature on the influence of ultrasonography probe on repeat prostate biopsy is non-existent, the present study adds information which may help urologists improve their chances of detecting prostate cancer on prostate biopsy. Determining which type of probe to use on a prostate biopsy is a simple external factor that may help improve patient management. OBJECTIVE: To determine if the type of transrectal ultrasonography (TRUS) probe used during repeat prostate biopsy influences prostate cancer detection rates. PATIENTS AND METHODS: We conducted a retrospective chart review of 680 men undergoing repeat prostate biopsy at our institution between 2000 and 2010. Patient mean (range) age was 64.2 (39-95) years. The median (range) prostate-specific antigen (PSA) level was 5.5 (0.37 33.8) ng/mL and median (range) free PSA was 17 (5-45) %. Patient age, PSA, prostate volume, number of biopsy cores, time interval between initial and repeat biopsy, digital rectal examination and pathological findings were all included in a multivariate logistic regression analysis. RESULTS: The use of an end-fire probe on repeat biopsy significantly increased prostate cancer detection (odds ratio [OR] 1.59, 95% confidence interval [CI]: 1.03-2.46). The time interval between 1(st) and 2(nd) biopsy was also significant (OR 1.46, 95% CI: 1.11-1.09). On univariate analysis, white race (OR 0.66, 95% CI: 0.44-0.99), increasing prostate volume (OR 0.70, 95% CI: 0.55-0.89), and higher free PSA (OR 0.54, 95% CI: 0.34-0.84) were associated with a decreased risk of cancer. When evaluating the different permutations of using an end-fire or side-fire probe on initial or repeat biopsy, there was no difference in prostate cancer detection regardless of order of use of an end-fire or side-fire probe. CONCLUSIONS: An end-fire probe is associated with improved prostate cancer detection rates on both initial and repeat biopsy. The order of probe use does not appear to matter. PMID- 22044502 TI - Prevalence of metabolic syndrome in patients with schizophrenia, and metabolic changes after 3 months of treatment with antipsychotics--results from a German observational study. AB - BACKGROUND: This observational study explored the prevalence of metabolic syndrome (MetS) in adult in- and outpatients with untreated or treated schizophrenia at baseline, and month-3 after initiation or switch of antipsychotic treatment. METHODS: MetS-prevalence (AHA/NHLB-definition) was assessed and Clopper-Pearson 95% confidence intervals (CIs) were calculated. Factors associated with MetS were explored through univariate and multivariate logistic regressions (both visits). RESULTS: MetS-prevalence was 44.3% (CI 39.8;48.9) at baseline and 49.6% (CI 45.0;54.2) at month-3. Previously unmedicated patients showed the lowest baseline MetS-prevalence (24.7%, CI 18.3;32.1). MetS-prevalence was not significantly different, regardless if patients previously received typical or atypical antipsychotics. Increased MetS risk was associated with somatic comorbidity and non-smoking at both visits, and with non-psychiatric co-medication, male sex, and increased C-reactive protein at month-3. CONCLUSIONS: At baseline, MetS was most prevalent in patients with previous antipsychotic medication. Limited metabolic changes were observed 3 months after switch/initiation of antipsychotic therapy. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: n.a. PMID- 22044503 TI - Prevalence of uveitis in indigenous populations presenting to remote clinics of central Australia: the Central Australian Ocular Health Study. AB - BACKGROUND: To report the prevalence of current and previous uveitis within the indigenous population living within Central Australia. DESIGN: Population-based cross-sectional study in Central Australia. PARTICIPANTS: One thousand eight hundred and eighty-four subjects who identified themselves as indigenous Australians, presenting to the remote clinics during the 36-month period between July 2005 and June 2008. METHODS: Clinical assessments for active or previous uveitis were performed. Data were collected using a standardized form. MAIN OUTCOME MEASURES: Prevalence of various types of uveitis. RESULTS: Four of 1881 subjects had evidence of previous or current anterior uveitis, giving a prevalence for anterior uveitis of 0.21% (95% confidence interval, 0.01-0.42%). Eleven of 1854 patients had signs of previous posterior uveitis, giving a prevalence for posterior uveitis of 0.59% (95% confidence interval 0.24-0.94%). Nine of the 11 patients with posterior uveitis cases (82%) had presumed toxoplasma retinochoroiditis. There were no cases of intermediate uveitis or panuveitis observed in this study. There were no observed cases consistent with well-recognized clinical uveitic syndromes, such as Behcet's disease or Vogt Koyanagi-Harada syndrome. CONCLUSIONS: A distinct pattern of uveitis appears to be present among indigenous population of remote Central Australia. Posterior uveitis was commoner than anterior uveitis with a predominance of toxoplasma retinochoroiditis. Environmental factors appeared to be more important in this genetically distinct population, with infective causes and ocular trauma being the most common aetiologies of uveitis. PMID- 22044504 TI - An evaluation of statewide emergency department utilization following Tennessee Medicaid disenrollment. AB - OBJECTIVES: During a series of reforms to the Tennessee Medicaid expansion program (TennCare) in 2005, approximately 171,000 adults were disenrolled from Medicaid. The objective of this study was to examine the statewide effect of such a disenrollment on Tennessee emergency department (ED) utilization. METHODS: Administrative data on all ED visits in Tennessee from 2004 through 2006 were obtained from the State Emergency Department Database and State Inpatient Database under the Healthcare Utilization Project. Population statistics and uninsured estimates were obtained from the U.S. Census Bureau, and TennCare enrollment data were obtained from the State of Tennessee Department of TennCare. The proportion and rate of ED visits, assessed separately by payer type, were compared across a predisenrollment period from January 1, 2004, through July 31, 2005, and across a postdisenrollment period from August 1, 2005, through December 31, 2006. The proportion and rate of ED visits resulting in hospital admission, again assessed separately by payer type, were compared across the same disenrollment periods in a similar way. We fitted a series of linear models for the total number of ED visits and each proportion and rate, with various degrees of adjustment for seasonality and time trend. RESULTS: The mean number of ED visits was 45,662 per week during the predisenrollment period and 44,463 per week during the postdisenrollment period (mean difference = -1,199; 95% confidence interval [CI] -1,722 to -676). By payer category, there was a decrease of 3,119 visits per week by TennCare beneficiaries and an increase of 2,203 per week by the uninsured. After disenrollment, the absolute proportion of ED visits by TennCare beneficiaries significantly decreased by 6.2% (95% CI = -6.6% to -5.8%), and the absolute proportion of uninsured ED visits increased by 5.3% (95% CI = 4.9% to 5.7%). The rate of ED visits by TennCare beneficiaries decreased by 0.091 ED visits/person/year (95% CI = -0.136 to -0.046) in the disenrollment period when controlling for time and seasonality. The rate of ED visits among the uninsured increased by 0.038 ED visits/person/year (95% CI = 0.011 to 0.065) in the postdisenrollment period when controlling for cubic time trend. The proportion of all TennCare ED visits that resulted in hospital admission did not change significantly between the two periods after adjusting for time trend and seasonality. The proportion of uninsured ED visits resulting in hospital admission, however, significantly increased after disenrollment by 2.0% (95% CI = 1.8% to 2.2%) and by 0.6% (95% CI = 0.0% to 1.2%) after adjusting for time and seasonality. CONCLUSIONS: The TennCare disenrollment of 2005 was associated with a modest decrease in the number of total ED visits in Tennessee. However, the payer mix among the Tennessee ED population shifted abruptly. The increased rate of ED visits by Tennessee's uninsured and the increased proportion of uninsured ED visits leading to hospital admission suggest an increased burden of illness in this highly vulnerable population. PMID- 22044505 TI - Electrocardiogram shows reliable heart rates much earlier than pulse oximetry during neonatal resuscitation. AB - BACKGROUND: The aim of this study was to determine the usefulness of the three lead electrocardiogram (ECG) during neonatal resuscitation. METHODS: Both pulse oximetry (PO) and ECG were applied immediately after delivery to measure heart rate (HR). We reviewed video recordings of the respective monitors, and checked the time at which each monitor started to display reliable rate values. RESULTS: In 20 deliveries, ECG showed HR much earlier than PO (median 38 s vs 122 s after delivery). ECG displayed reliable HR throughout resuscitation. We were able to confirm the effectiveness of the initial respiratory support from the elevation in HR. CONCLUSIONS: ECG was a safe and reliable method for showing HR, and was used to determine the initiation and the effectiveness of resuscitation in the delivery room. PMID- 22044506 TI - Loop-mediated isothermal amplification for detection of porcine circovirus type 2. AB - BACKGROUND: Porcine circovirus type 2 (PCV2) is the primary causative agent of the emerging swine disease known as postweaning multisystemic wasting syndrome (PMWS). Nowadays, polymerase chain reaction (PCR) is still the most widespread technique in pathogen detection. Loop-mediated isothermal amplification (LAMP), a novel nucleic acid amplification method developed in 2000, will possibly replace PCR in the field of detection. To establish a LAMP method for rapid detection of PCV2, two pairs of primers were designed specially from the open reading frame 2 (ORF2) sequences of PCV2. A LAMP method for rapid detection of PCV2 was established. To compare with PCR, sensitivity and specificity of LAMP were evaluated using the optimized reaction system. The LAMP products could be determined by agarose gel electrophoresis or adding SYBR Green I dye. RESULTS: The amplification of LAMP could be obtained at 63 degrees C for 60 min. The detection limit was nearly 1 copy of DNA plasmid, more sensitive than PCR. There was no cross-reaction with porcine circovirus type 1 (PCV1), porcine pseudorabies virus (PRV) and porcine parvovirus (PPV) under the same conditions. CONCLUSIONS: LAMP is an useful rapid detection method with high sensitivity and specificity for PCV2. PMID- 22044507 TI - A neuroimaging proof of principle study of Down's syndrome and dementia: ethical and methodological challenges in intrusive research. AB - BACKGROUND: Research into specific illnesses and the development of new treatments may only become possible as new technologies become available. When used for research, such technologies may best be described as 'intrusive', in that they require a considerable willingness and commitment on the part of the participants. This has increasingly been the case for brain disorders and illnesses where novel neuroimaging techniques, often combined with clinical and psychological assessments, have the potential to result in new understanding. People with intellectual disabilities (ID) have a history of under-representation as participants in research using such technologies and are therefore at risk of not receiving equal access to state-of-the-art treatments. We propose that 'intrusive' biomedical research is both possible and ethical in ID, and explore some of the methodological challenges by reference to a recent proof of principle study that used a relatively new ligand-based brain scanning technique in a group of volunteers with Down's syndrome. METHODS: Five overlapping stages of the study methodology were identified and evaluated for their acceptability to volunteers with mild to moderate ID through discussion, reflection, and analysis of structured feedback in the context of key policy documents, ethical guidelines and relevant legislation. RESULTS: Identification of key ethical and methodological challenges from reflective practice and participant feedback facilitated the emergence of strategies that permitted continual refinement of the study design. Important areas considered included (1) being clear about the purpose and scientific justification for the study; (2) reconciling the potential risks and benefits with relevant ethical guidelines and legislation; (3) identifying and implementing effective recruitment strategies; (4) optimising and assessing capacity to consent; and (5) making the 'intrusive' procedures as acceptable as possible to people with ID. CONCLUSION: We were able to demonstrate that a proof of principle study incorporating a novel brain scanning technique in a group of volunteers with ID was feasible, safe and well tolerated, despite the vulnerabilities of the study cohort and the intrusive nature of the research. We consider the study within an ethical and historical discourse about the principles that define current 'best practice' in ID research and propose a number of key recommendations for making intrusive research acceptable in people with ID. PMID- 22044508 TI - Funding and infrastructure among large-scale clinical trials examining cardiovascular diseases in Japan: evidence from a questionnaire survey. AB - BACKGROUND: Large-scale clinical trials with thousands of participants are often needed to evaluate the risk reductions of cardiac events and/or death. Many recent clinical trials have evaluated the incidences of cardiac events using hard endpoints, especially in cardiovascular and metabolic medicine. A high investigation cost is involved in conducting a large-scale clinical trial, and obtaining sufficient funding is essential. The infrastructural environment of clinical trials is currently inadequate in Japan. We conducted a questionnaire based survey to address this issue. The present study sought to clarify the current situation surrounding large-scale clinical trials in terms of funding and infrastructure, and to inform discussion about improving the financial and infrastructural situation for clinical trials. METHODS: We sent questionnaires to 119 sponsors of large-scale clinical trials between August 2007 and December 2007, and between July 2009 and August 2009. Answers to each question were summarized and data were statistically analyzed. RESULTS: We received responses from the sponsors of 63 (52.9%) out of 119 trials to which questionnaires were sent. The results revealed that 25 trials (39.7%) were funded by foundations, and 21 trials (33.3%) were funded by public agencies. All of the foundations involved in conducting clinical trials, where funding sources were specified, were funded by private organizations such as pharmaceutical companies. All of the clinical trials with a cost of JPY 300 million (USD 3.27 million) or more were funded by private organizations, and none were funded solely by public agencies. The sponsors of 23 trials (36.5%) responded that the trial was 'not registered' to clinical trial registry. CONCLUSIONS: The questionnaire responses revealed that there were still many trials whose funding sources were unclear and many sponsors were unaware of their responsibilities in managing and/or financing the costs of clinical trials. These findings indicate that further discussion is required to establish appropriate frameworks and/or rules regarding funding, while considering conflicts of interest. This discussion should take place as soon as possible to facilitate appropriate clinical trials. PMID- 22044509 TI - An accessory mitral valve leaflet causing left ventricular outflow tract obstruction and associated with severe aortic incompetence. AB - This case report describes a 20-year-old woman with Turner's syndrome who presented with reduced effort tolerance limited by dyspnea. She had previously been on pediatric cardiology follow-up for congenital subvalvular aortic stenosis first diagnosed at age 7. Unfortunately she defaulted after two visits before any intervention could be done. Transthoracic echocardiography demonstrated severe aortic incompetence (AI) with a membrane-like structure in the left ventricular outflow tract (LVOT). The mean pressure gradient across the LVOT on continuous wave Doppler was 41 mmHg. The membranous interventricular septum appeared aneurysmal and it was observed that the "subaortic membrane" had a connection to the anterolateral papillary muscle via a strand of chordal tissue. Further images were captured using two-dimensional and three-dimensional transthoracic and transesophageal echocardiography (iE33, Philips Medical Systems, Andover, MA, USA). After a review of the literature it was concluded that this appeared to be an accessory mitral valve (AMV) leaflet causing LVOT obstruction associated with AI. AMV tissue is a rare congenital malformation causing LVOT obstruction. Because it is so unusual, it may not be immediately recognizable even in a high volume echocardiography laboratory. The clue which helped with the diagnosis was the strand of chordal tissue which connected the mass to the papillary muscle. This anomaly is often associated with LVOT obstruction. PMID- 22044510 TI - Limited sampling strategies for the estimation of atazanavir daily exposure in HIV-infected patients. AB - Stepwise multiple regression analyses were applied to 44 atazanavir pharmacokinetic profiles from 44 HIV-1 infected patients concomitantly treated with raltegravir with the goal of identifying limited sampling strategies for the prediction of drug AUC(0-12) . Atazanavir trough-based equations failed to reliably predict daily drug exposure in patients with low drug bioavailability. Conversely, different algorithms based on few samples and associated with good correlation, acceptable bias and imprecision with the measured atazanavir AUC(0 12) were identified. These models could be used to predict atazanavir exposure for clinic or research purposes. PMID- 22044511 TI - Molecular dynamics simulations and in silico peptide ligand screening of the Elk 1 ETS domain. AB - BACKGROUND: The Elk-1 transcription factor is a member of a group of proteins called ternary complex factors, which serve as a paradigm for gene regulation in response to extracellular signals. Its deregulation has been linked to multiple human diseases including the development of tumours. The work herein aims to inform the design of potential peptidomimetic compounds that can inhibit the formation of the Elk-1 dimer, which is key to Elk-1 stability. We have conducted molecular dynamics simulations of the Elk-1 ETS domain followed by virtual screening. RESULTS: We show the ETS dimerisation site undergoes conformational reorganisation at the alpha1beta1 loop. Through exhaustive screening of di- and tri-peptide libraries against a collection of ETS domain conformations representing the dynamics of the loop, we identified a series of potential binders for the Elk-1 dimer interface. The di-peptides showed no particular preference toward the binding site; however, the tri-peptides made specific interactions with residues: Glu17, Gln18 and Arg49 that are pivotal to the dimer interface. CONCLUSIONS: We have shown molecular dynamics simulations can be combined with virtual peptide screening to obtain an exhaustive docking protocol that incorporates dynamic fluctuations in a receptor. Based on our findings, we suggest experimental binding studies to be performed on the 12 SILE ranked tri peptides as possible compounds for the design of inhibitors of Elk-1 dimerisation. It would also be reasonable to consider the score-ranked tri peptides as a comparative test to establish whether peptide size is a determinant factor of binding to the ETS domain. PMID- 22044512 TI - The prevalence of idiopathic hirsutism and polycystic ovary syndrome in the Tehran Lipid and Glucose Study. AB - BACKGROUND: There is no clear and contemporaneous method for screening of idiopathic hirsutism (IH) and polycystic ovary syndrome (PCOS) at the community level and current estimates regarding their prevalence are limited. We aimed to ascertain the prevalence of IH and PCOS in a randomly selected sample of reproductive aged female participants of the Tehran Lipid and Glucose Study (TLGS). METHODS: One thousand and two women, aged 18-45 years, were randomly selected from among reproductive aged women who participated in the TLGS. Those women with either hirsutism or menstrual dysfunction were assessed for biochemical hyperandrogenemia; whereas those participants with hirsutism per se were further assessed for subclinical menstrual dysfunction. PCOS were diagnosed using the National Institute of Health (NIH) criteria. IH was defined as hirsutism without clinical or sub clinical menstrual dysfunction or biochemical hyperandrogenemia (BH). RESULTS: The mean+/-SD of age of study population was 29.2+/-8.7 years. Estimated prevalences of idiopathic hirsutism and pure menstrual dysfunction were 13.0% (95% CI: 10.9%-15.1%) and 1.5%(95% CI: 1.1% 1.9%), respectively. The prevalence of PCOS was 8.5% (95% CI: 6.8%-10.2%); more than one third of these cases would possibly have remained undiagnosed or misdiagnosed, had we not assessed them for subclinical menstrual dysfunction or biochemical hyperandrogenemia. CONCLUSIONS: These data from a large representative and non selected population of women confirm the concept that IH and PCOS are the two most common gynecological endocrinopathies among reproductive aged women. The estimated prevalence of these conditions is highly influenced by their screening methods at the community level. PMID- 22044513 TI - The panzootic white-nose syndrome: an environmentally constrained disease? AB - White-nose syndrome (WNS) is an emerging disease of hibernating bats probably caused by a pathogenic fungus, Geomyces destructans. The fungus has dispersed rapidly in the Northeastern United States and Canada and is presently a serious risk to hibernating bats of the mid-southern United States. Our objectives were to investigate how the environmental factors of temperature and resources impact the physiology of bats and apply this to explore possible effects of the fungus G. destructans on bats. Using a dynamic, physiologically based model parameterized for little brown bats (Myotis lucifugus), we found that the survival region defined in terms of minimal and maximal cave temperatures and bat lipid reserve levels exhibits plasticity as a function of cave temperature. During the pre-hibernation period, constellations of increased availability of fall and winter prey, reduced energy expenditure and lipogenic factors provide fat deposition in hibernator species that engender survival throughout the hibernation period. The model-derived survival region is used to demonstrate that small increases in lipid reserves allow survival under increasing maximum temperatures, which provides flexibility of bat persistence at the higher cave temperature ranges that may occur in the Southern United States. Antipodally, the lower-temperature survival range is bounded with minimum temperatures. Our results suggest that there is an environmental distinction between survival of bats in Southern and Northern US states, a relationship that could prove very important in managing WNS and its dispersal. PMID- 22044514 TI - Laparoscopic pancreatic necrosectomy in a child with severe acute pancreatitis. AB - Acute pancreatitis (AP) in children usually follows a mild course but occasionally may be severally problematic. We report the case of a 12-year-old boy with severe AP who was managed with repeated laparoscopic pancreatic necrosectomy. Three weeks later he represented with a pancreatic pseudocyst that was treated with endoscopic gastrocystotomy. His abdominal pain persisted and a subsequent magnetic resonance cholangiopancreatogram showed multiple gallbladder and common bile duct (CBD) stones that were missed on previous imaging investigations. He underwent laparoscopic cholecystectomy with transcystic exploration of the CBD. The patient is currently well, more than 2 years following the definitive corrective surgery. To the best of our knowledge, this is the first case of laparoscopic pancreatic necrosectomy in a child. PMID- 22044515 TI - Enhanced BDNF serum levels in patients with severe pathological gambling. AB - Although the pathophysiology of gambling is unknown, an involvement of midbrain dopaminergic pathway has been hypothesized. In this study, the association between brain-derived neurotrophic factor (BDNF) and pathological gambling was investigated. We measured BDNF serum levels in (1) video players (n=10); (2) card players (n=9); (3) mixed players (n=21; both video and card players) and (4) age matched controls (n=18). Mixed players had increased BDNF serum levels as compared to controls and higher South Oaks Gambling Screen score as compared to card or video players. Thus, the data demonstrate that patients affected by severe pathological gambling show enhanced BDNF serum levels. PMID- 22044516 TI - Intravenous pyogenic granuloma originating in the renal vein. PMID- 22044517 TI - Predictors for poststroke outcomes: the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study protocol. AB - BACKGROUND: Recent studies have demonstrated that even survivors of mild stroke experience residual damage, which persists and in fact increases in subsequent years. About 45% of stroke victims remain with different levels of disability. Identifying factors associated with poststroke cognitive and neurological decline could potentially yield more effective therapeutic opportunities. AIMS AND HYPOTHESIS: We hypothesize that data based on biochemical, neuroimaging, genetic and psychological measures can, in aggregate, serve as better predictors for subsequent disability, cognitive and neurological deterioration, and suggest possible interventions. DESIGN: The Tel-Aviv Brain Acute Stroke Cohort (TABASCO) study is an ongoing, prospective cohort study that will recruit approximately 1125 consecutive first-ever mild-moderate stroke patients. It is designed to evaluate the association between predefined demographic, psychological, inflammatory, biochemical, neuroimaging and genetic markers, measured during the acute phase, and long-term outcome: subsequent cognitive deterioration, vascular events (including recurrent strokes), falls, affect changes, functional everyday difficulties and mortality. DISCUSSION: This study is an attempt to comprehensively investigate the long-term outcome of mild-moderate strokes. Its prospective design will provide quantitative data on stroke recurrence, the incidence of other vascular events and the evaluation of cognitive, affective and functional decline. Identifying the factors associated with poststroke cognitive and functional decline could potentially yield more effective therapeutic approaches. PMID- 22044518 TI - Good places for ageing in place: development of objective built environment measures for investigating links with older people's wellbeing. AB - BACKGROUND: There is renewed interest in the role of the built environment in public health. Relatively little research to date investigates its impact on healthy ageing. Ageing in place has been adopted as a key strategy for coping with the challenges of longevity. What is needed is a better understanding of how individual characteristics of older people's residential environments (from front door to wider neighbourhood) contribute to their wellbeing, in order to provide the basis for evidence-based housing/urban design and development of interventions. This research aimed to develop a tool to objectively measure a large range of built environment characteristics, as the basis for a preliminary study of potential relationships with a number of 'place-related' functional, emotional and social wellbeing constructs. METHODS: Through a review of urban design literature, design documents, and existing measures, a new tool, the NeDeCC (Neighbourhood Design Characteristics Checklist) was developed. It was piloted, refined, and its reliability validated through inter-rater tests. A range of place-related wellbeing constructs were identified and measured through interviews with 200 older people living in a wide variety of rural-urban environments and different types of housing in England. The NeDeCC was used to measure the residential environment of each participant, and significant bivariate relationships with wellbeing variables were identified. RESULTS: The NeDeCC was found to have convincing face and construct validity and good inter rater and test/retest reliability, though it would benefit from use of digital data sources such as Google Earth to eliminate the need for on-site survey. The significant relationships found in the study suggest that there may be characteristics of residential environments of potential relevance for older people's lives that have been overlooked in research to date, and that it may be worthwhile to question some of the assumptions about where and how older people want to live (e.g. villages seem to be positive). They also point to the importance of considering non-linear relationships. CONCLUSIONS: The NeDeCC provides the basis for generation of evidence-based design guidance if it is used in prospective controlled studies or 'natural experiments' in the future. Ultimately, this will facilitate the creation of better places for ageing in place. PMID- 22044519 TI - Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series. AB - Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non-clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer specific survival (CSS) probabilities compared with ccRCC. However, an independent prognostic role of RCC histotype was not confirmed in some large multicenter series and only a few studies have focused on the oncological outcomes of ChRCC. The present study is one of the few to evaluate cancer-related outcomes of ChRCC and represents to our knowledge the largest series of ChRCCs. Consequently, the present findings may assist in elucidating the natural history of surgically treated ChRCC. The present study confirms that ChRCCs have good prognosis and a low tendency to progress and metastasize. Only 1.3% of patients presented with distant metastases at diagnosis, and the 5- and 10-year CSS were 93% and 88.9%, respectively. However, although ChRCCs are generally characterised by an excellent prognosis, we observed that patients with locally advanced or metastatic cancers as well as those with sarcomatoid differentiation have a poor outcome. The study also investigated prognostic factors for recurrence-free survival (RFS) and CSS for this RCC histotype. The definition of outcome predictors can be useful for patient counselling, planning of follow-up strategies, and patient selection for clinical trials. In the present study, gender, clinical T stage, pathological T stage, and presence of sarcomatoid differentiation were significantly associated with RFS and CSS at multivariable analysis. We also identified N/M stage as an independent predictor of CSS. Notably, as Fuhrman grade was not an independent predictor of cancer-related outcomes, the present study confirms that this histological variable is not a reliable prognostic factor for ChRCC. OBJECTIVES: To investigate cancer-related outcomes of chromophobe renal cell carcinoma (ChRCC) in a large multicentre dataset. To determine prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS) for this RCC histological type. PATIENTS AND METHODS: In all, 291 patients with ChRCC were identified from a multi institutional retrospective database including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007. Univariable and multivariable Cox regression models were used to identify prognostic factors predictive of RFS and CSS after surgery for ChRCC. RESULTS: At a median follow-up of 44 months, 25 patients (8.6%) had disease recurrence and 18 patients (6.2%) died from disease. The 5-year RFS and CSS rates were 89.3% and 93%, respectively. Gender (P= 0.014), clinical T stage (P= 0.017), pathological T stage (P= 0.003), and sarcomatoid differentiation (P= 0.032) were independent predictors of RFS at multivariable analysis. For CSS, there was an independent prognostic role for gender (P= 0.032) and T stage (P= 0.019) among the clinical variables and for T stage (P= 0.016), N/M stage (P= 0.023), and sarcomatoid differentiation (P= 0.015) among the pathological variables. CONCLUSIONS: Patients with ChRCC have a low risk of tumour progression, metastasis, and cancer-specific death. Patient gender, clinical and pathological tumour stage, and sarcomatoid differentiation are significant predictors of RFS and CSS for ChRCC. PMID- 22044520 TI - Orbicularis oculi: morphological changes mimicking mitochondrial cytopathy in a series of control normal muscles. AB - INTRODUCTION: Orbicularis oculi (OO) muscle has recently proposed as a suitable muscle for biopsy to diagnose mitochondrial cyopathy: METHODS: Enzyme histochemical and immunohistochemical studies were performed on OO muscle obtained from 18 patients aged 37-87 years (median 64 years), 6 males, 12 females, who were undergoing routine upper blepharoplasty surgery. RESULTS: We confirmed the marked type II fibre (fast myosin heavy chain) predominance (89%) but also noted a different proportion and distribution of mitochondria in these fibres with occasional pseudo-'ragged-red' fibres with prominent subsarcolemmal and cytoplasmic aggregation of mitochondria. Cytochrome oxidase-negative fibres and true 'ragged-red' fibres were found at all ages over 40 years at levels that approach those used for diagnosis of mitochondrial cytopathy in peripheral or limb skeletal muscles. CONCLUSION: We would therefore urge caution in the use of OO as muscle biopsy for diagnosis of mitochondrial cytopathy and advise concomitant biopsy of limb skeletal muscle and/or supplementary genetic studies. PMID- 22044521 TI - Factors identifying risk for psychological distress in the civilian trauma population. AB - OBJECTIVES: The emergency department (ED) is a valuable setting to initiate intervention to prevent future complications following traumatic injury. Posttraumatic stress disorder (PTSD) occurs in 10% to 40% of patients after single-incident civilian trauma. Prior research suggests that young age is associated with increased risk. We hypothesized that other factors correlated with age may be responsible. The aim of this study was to determine if factors identifiable in the ED can better explain the relationship between younger age and PTSD, therefore more specifically identifying those at risk for long-term distress. METHODS: The influence of age on PTSD severity scores was isolated using data from an established screening program for all admitted trauma patients at a Level I trauma center. The PTSD Checklist-Civilian (PCLC) was administered prospectively to 527 adult trauma patients to measure PTSD symptom severity immediately posttrauma. Patient and trauma characteristics were then reviewed using medical records. Hierarchical linear regression modeled and evaluated the independent association of age with PTSD symptom severity and explored additional variables as better predictors of risk. RESULTS: PTSD symptom severity was associated individually with younger age, ethnic minority status, assaultive trauma, unemployment, low household income, and being unmarried, but not with sex, Injury Severity Score (ISS), or Glasgow Coma Scale (GCS) score at the scene. Multivariate analysis demonstrated assaultive trauma and lower socioeconomic status (SES) were best associated with greater PCLC scores, accounting for 9.3% of the variance. Age did not account for additional variance. CONCLUSIONS: Although young age is associated with increased PTSD symptom severity scores, characteristics associated with young age, specifically assaultive trauma and low SES, account for this risk. Young age is not an independent risk factor for PTSD. Psychological assessment in the ED can be targeted toward assaultive trauma patients, especially those of low SES, to establish early intervention and hopefully prevent the development of PTSD. PMID- 22044523 TI - Focus on elder mistreatment and abuse. PMID- 22044522 TI - Tuberculosis genotyping information management system: enhancing tuberculosis surveillance in the United States. AB - Molecular characterization of Mycobacterium tuberculosis complex isolates (genotyping) can be used by public health programs to more readily identify tuberculosis (TB) transmission. The Centers for Disease Control and Prevention's National Tuberculosis Genotyping Service has offered M. tuberculosis genotyping for every culture-confirmed case in the United States since 2004. The TB Genotyping Information Management System (TB GIMS), launched in March 2010, is a secure online database containing genotype results linked with case characteristics from the national TB registry for state and local TB programs to access, manage and analyze these data. As of September 2011, TB GIMS contains genotype results for 89% of all culture-positive TB cases for 2010. Over 400 users can generate local and national reports and maps using TB GIMS. Automated alerts on geospatially concentrated cases with matching genotypes that may represent outbreaks are also generated by TB GIMS. TB genotyping results are available to enhance national TB surveillance and apply genotyping results to conduct TB control activities in the United States. PMID- 22044527 TI - Evidence-based practice guideline: elder abuse prevention. PMID- 22044529 TI - The effects of hypertonic fluid administration on the gene expression of inflammatory mediators in circulating leucocytes in patients with septic shock: a preliminary study. AB - OBJECTIVE: This study was designed to investigate the effect of hypertonic fluid administration on inflammatory mediator gene expression in patients with septic shock. DESIGN AND SETTING: Prospective, randomized, controlled, double-blind clinical study in a 15-bed mixed intensive care unit in a tertiary referral teaching hospital. INTERVENTIONS: Twenty-four patients, who met standard criteria for septic shock, were randomized to receive a bolus of hypertonic fluid (HT, 250 ml 6% HES/7.2% NaCl) or isotonic fluid (IT, 500 ml 6% HES/0.9% NaCl) administered over 15 minutes. Randomization and study fluid administration was within 24 hours of ICU admission for all patients. This trial is registered with ANZCTR.org.au as ACTRN12607000259448. RESULTS: Blood samples were taken immediately before and 4, 8, 12, and 24 hours after fluid administration. Real-time reverse transcriptase polymerase chain reaction (RT rtPCR) was used to quantify mRNA expression of different inflammatory mediators in peripheral leukocytes. In the HT group, compared with the IT group, levels of gene expression of MMP9 and L-selectin were significantly suppressed (p = 0.0002 and p = 0.007, respectively), and CD11b gene expression tended to be elevated (p = NS). No differences were found in the other mediators examined. CONCLUSIONS: In septic shock patients, hypertonic fluid administration compared with isotonic fluid may modulate expression of genes that are implicated in leukocyte-endothelial interaction and capillary leakage.The study was performed at the Intensive Care Department, Waikato Hospital, and at the Molecular Genetics Laboratory, University of Waikato, Hamilton, New Zealand. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000259448. PMID- 22044530 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin's suppression of 1-nitropyrene-induced p53 expression is mediated by cytochrome P450 1A1. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 1-nitropyrene (1-NP), and benzo[a]pyrene (BaP) are toxic environmental pollutants. TCDD was shown to suppress p53 expression in response to genotoxic stress and hypoxic conditions. However, the mechanism of TCDD's actions is not clearly understood. Our data showed that pretreatment with TCDD abolished 1-NP- but not BaP-induced p53 and mouse double minute 2 (MDM2; HDM2 in humans) expressions. TCDD suppressed 1-NP- but not BaP-induced p53 activity, and in contrast, pifithrin-alpha (PFT-alpha), a p53 inhibitor, suppressed both 1-NP- and BaP-induced p53 activity. In the presence of nutlin-3, an HDM2 inhibitor, TCDD was still able to suppress 1-NP induced p53 expression. However, TCDD-activated HDM2 did not distinctly cause the degradation of BaP- or nutlin-3-induced p53 expression. Accordingly, TCDD's suppression of 1-NP-induced p53 expression was compound-specific, and the contribution of HDM2 to the abolition of 1-NP-induced p53 was limited. beta Naphthoflavon (beta-NF), an aryl hydrocarbon receptor (AHR) agonist, mimicked TCDD's action and abolished 1-NP-induced p53 expression. In the presence of CH 223191, an AHR antagonist, TCDD was unable to abolish 1-NP-induced p53 expression. Results indicate that activation of the AHR is required for TCDD's suppression of 1-NP's induction of p53. Cytochrome P450 (CYP) 1A1 is an AHR targeting gene and a xenobiotic-metabolizing enzyme. TCDD was unable to abolish 1 NP's induction of p53 in CYP1A1-deficient cells, the CYP1A1 transcript of which was degraded by small hairpin RNA-CYP1A1. Both TCDD and PFT-alpha are potent CYP1A1 inducers and decreased 1-NP-induced cell death and mutagenesis. In summary, TCDD induced detoxification of 1-NP's toxicity, which was mediated by the CYP1A1 enzyme. PMID- 22044531 TI - Improvement of cognitive flexibility and cingulate blood flow correlates after atypical antipsychotic treatment in drug-naive patients with first-episode schizophrenia. AB - The aim of this study was to examine the changes in cognitive flexibility and associated cerebral blood flow in the anterior cingulate lobe of drug-naive patients with first-episode schizophrenia who were treated with atypical antipsychotics for 6 weeks. Single photon emission computed tomography (SPECT) images were obtained from 8 healthy subjects both at rest and while performing the flexibility subtest of the TAP (Test for Attentional Performance). SPECT images were obtained in parallel from 8 first-episode drug-naive schizophrenic patients while they were performing the same task both before and after 6 weeks of neuroleptic treatment. In the control group, an increase in the perfusion indices of the dorsal section of the anterior cingulate gyrus was observed in the activation condition. Task performance was altered and the level of perfusion of the brain region related to the task execution was significantly decreased in the patients at baseline. After treatment, there was a significant improvement in both task performance and the level of perfusion of the dorsal section of the anterior cingulate. We conclude that treatment with second-generation neuroleptics improves cognitive flexibility, and there was a relationship between such improvements and normalization of perfusion indices of the involved brain areas. PMID- 22044532 TI - Dissociating behavioral disorders in early dementia-An FDG-PET study. AB - Behavioral impairments occur frequently in dementia. Studies with magnetic resonance imaging, measuring atrophy, have systematically investigated their neural correlates. Such a systematic approach has not yet been applied to imaging with [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET), although regional hypometabolism may precede and exceed atrophy in dementia. The present study related all behavioral disorders as assessed with the Neuropsychiatric Inventory to reductions in brain glucose utilization as measured by FDG-PET with Statistical Parametric Mapping (SPM5). It included 54 subjects mainly with early Alzheimer's disease, frontotemporal lobar degeneration, and subjective cognitive impairment. Apathy, disinhibition and eating disorders - most frequent in frontotemporal lobar degeneration - correlated significantly with regional brain hypometabolism. Whereas a single regressor analysis and conjunction analysis revealed largely overlapping frontomedian regions that were associated with all three behavioral domains, a disjunction analysis identified three specific neural networks for each behavioral disorder, independent of dementia severity. Apathy was related to the ventral tegmental area, a component of the motivational dopaminergic network; disinhibition to both anterior temporal lobes including the anterior hippocampi and left amygdala, caudate head, orbitofrontal cortex and insulae; and eating disorders to the right lateral (orbito) frontal cortex/insula. Our study contributes to the understanding of behavioral deficits in early dementia and suggests specific diagnostic and therapeutic approaches. PMID- 22044533 TI - Striatal dopamine transporter binding for predicting the development of delayed neuropsychological sequelae in suicide attempters by carbon monoxide poisoning: A SPECT study. AB - Carbon monoxide poisoning (COP) after charcoal burning results in delayed neuropsychological sequelae (DNS), which show clinical resemblance to Parkinson's disease, without adequate predictors at present. This study examined the role of dopamine transporter (DAT) binding for the prediction of DNS. Twenty-seven suicide attempters with COP were recruited. Seven of them developed DNS, while the remainder did not. The striatal DAT binding was measured by single photon emission computed tomography with (99m)Tc-TRODAT. The specific uptake ratio was derived based on a ratio equilibrium model. Using a logistic regression model, multiple clinical variables were examined as potential predictors for DNS. COP patients with DNS had a lower binding on left striatal DAT binding than patients without DNS. Logistic regression analysis showed that a combination of initial loss of consciousness and lower left striatal DAT binding predicted the development of DNS. Our data indicate that the left striatal DAT binding could help to predict the development of DNS. This finding not only demonstrates the feasibility of brain imaging techniques for predicting the development of DNS but will also help clinicians to improve the quality of care for COP patients. PMID- 22044534 TI - Gid9, a second RING finger protein contributes to the ubiquitin ligase activity of the Gid complex required for catabolite degradation. AB - The two major antagonistic pathways of carbon metabolism in cells, glycolysis and gluconeogenesis, are tightly regulated. In the eukaryotic model organism Saccharomyces cerevisiae the switch from gluconeogenesis to glycolysis is brought about by proteasomal degradation of the gluconeogenic enzyme fructose-1,6 bisphosphatase. The ubiquitin ligase responsible for polyubiquitylation of fructose-1,6-bisphosphatase is the Gid complex. This complex consists of seven subunits of which subunit Gid2/Rmd5 contains a RING finger domain providing E3 ligase activity. Here we identify an additional subunit containing a degenerated RING finger, Gid9/Fyv10. This subunit binds to Gid2/Rmd5. A mutation in the degenerated RING finger of Gid9/Fyv10 abolishes polyubiquitylation and degradation of three enzymes specific for gluconeogenesis. PMID- 22044535 TI - BLT2 phosphorylation at Thr355 by Akt is necessary for BLT2-mediated chemotaxis. AB - BLT2, a low-affinity leukotriene B(4) (LTB(4)) receptor, is a member of the G protein-coupled receptor family and is involved in multiple cellular responses, including chemotaxis. Despite its biological significance, the mechanisms of BLT2 regulation, especially by protein kinases, are poorly characterised. In this study, we found that Akt phosphorylates BLT2 at its C-terminal Thr(355) residue and that this event is critical for BLT2-mediated chemotactic responses. In addition, we found that Rac1 stimulation and subsequent reactive oxygen species (ROS) production lie downstream of BLT2 phosphorylation, thus mediating chemotaxis. PMID- 22044536 TI - Understanding adolescent and young adult use of family physician services: a cross-sectional analysis of the Canadian Community Health Survey. AB - BACKGROUND: Primary health care is known to have positive effects on population health and may reduce at-risk behavior and health problems in adolescence. Yet little is known about the factors that are associated with adolescent and young adult utilization of family physician services. It is critical to determine the factors associated with utilization to inform effective primary health care policy. We address this gap in the primary health care literature by examining three issues concerning adolescent and young adult family physician use: inequity; the unique developmental stage of adolescence; and the distinction between utilization (users versus non-users) and intensity (high users versus low users). METHODS: We conducted nested logistic regressions for two outcomes: utilization and intensity of family physician services for early adolescence, middle adolescence, and young adulthood using the 2005 Canadian Community Health Survey. RESULTS: Chronic conditions were associated with utilization in early and middle adolescence and intensity in all age groups. Respondents from Quebec had lower odds of utilization. Those without a regular medical doctor had much lower odds of being users. The factors associated with use in early and middle adolescence were in keeping with parental involvement while the factors in young adulthood show the emerging independence of this group. CONCLUSIONS: We highlight key messages not known previously for adolescent and young adult use of family physician services. There is inequity concerning regional variation and for those who do not have a regular medical doctor. There is variation in factors associated with family physician services across the three age groups of adolescence. Health care and health care policies aimed at younger adolescents must consider that parents are still the primary decision-maker while older adolescents are more autonomous. There is variation in the factors associated with the two outcomes of utilization and intensity of services. Factors associated with utilization must be understood when considering the equitability of access to primary health care while factors associated with intensity must be understood when considering appropriate use of resources. The understanding gained from this study can inform health care policy that is responsive to the critical developmental stage of adolescence and young adulthood. PMID- 22044537 TI - A model for predicting size distributions delivered from pMDIs with suspended drug. AB - A new model has been developed for predicting size distributions delivered from pressurized metered dose inhalers (pMDIs) that contain suspended drug particles. This model enables the residual particle size distribution to be predicted for a broad range of formulations. It expands on previous models by allowing for polydisperse micronized input drug, multiple suspended drugs, dissolved drug, and dissolved or suspended excipient to be included in the formulation. The model indicates that for most pMDI configurations, the majority of droplets contain no drug or a single drug particle and the residual particle size distribution delivered from the pMDI is essentially equivalent to the size distribution of the micronized drug used in the formulation. However, for pMDIs with a high drug concentration or that use small micronized drug particles, there can be a substantial fraction of the droplets that contain multiple drug particles. The residual particle size distribution obtained from these pMDIs can be substantially larger than the size distribution of the micronized drug. Excellent agreement was observed between size distributions predicted using this model and those obtained from experimental cascade impactor measurements (r(2)=0.97), thus demonstrating the ability of the model to accurately predict the size distributions obtained from suspension pMDIs. PMID- 22044538 TI - Dissolution of solid lipid extrudates in biorelevant media. AB - Solid lipid extrudates with the model drug praziquantel were produced with chemically diverse lipids and investigated regarding their dissolution behaviour in different media. The lipids used in this study were glyceryl tripalmitate, glyceryl dibehenate, glyceryl monostearate, cetyl palmitate and solid paraffin. Thermoanalytical and dissolution behaviour was investigated directly after extrusion and after 3 and 6 months open storage at 40 degrees C/75% RH. Dissolution studies were conducted in hydrochloric acid (HCl) pH 1.2 with different levels of polysorbate 20 and with a biorelevant medium containing pancreatic lipase, bile salts and phospholipids. Furthermore, the impact of lipid digestion on drug release was studied using in vitro lipolysis. The release of praziquantel from cetyl palmitate and glyceryl monostearate in the biorelevant medium was much faster than in HCl, whereas there was hardly any difference for the other lipids. It was shown that drug release from glyceryl monostearate matrices is driven by both solubilisation and enzymatic degradation of the lipid, whereas dissolution from cetyl palmitate extrudates is dependent only on solubilisation by surfactants in the medium. Moreover, storage influenced the appearance of the extrudate surface and the dissolution rate for all lipids except solid paraffin. PMID- 22044539 TI - Reverse aqueous microemulsions in hydrofluoroalkane propellants and their aerosol characteristics. AB - In this work we describe the structure and environment of reverse aqueous microemulsions formed in 1,1,1,2-tetrafluoroethane (HFA134a) propellant in the presence of a non-ionic ethoxylated copolymer, and the aerosol characteristics of the corresponding pressurized metered dose inhaler (pMDI) formulations. The activity of selected polypropylene oxide-polyethylene oxide-polypropylene oxide (PO(m)EO(n)PO(m)) amphiphiles at the HFA134a-water interface was studied using in situ high-pressure tensiometry, and those results were used as a guide in the selection of the most appropriate candidate surfactant for the formation of microemulsions in the compressed HFA134a. The environment and structure of the aggregates formed with the selected surfactant candidate, PO(22)EO(14)PO(22), was probed via UV-vis spectroscopy (molecular probe), and small angle neutron scattering (SANS), respectively. High water loading capacity in the core of the nanoaggregates was achieved in the presence of ethanol. At a water-to-surfactant molar ratio of 21 and 10% ethanol, cylindrical aggregates with a radius of 18A, and length of 254A were confirmed with SANS. Anderson Cascade Impactor (ACI) results reveal that the concentration of the excipients (C(exp), including surfactant, water and ethanol) has a strong effect on the aerosol characteristics of the formulations, including the respirable fraction, and the mass mean aerodynamic diameter (MMAD), and that the trend in MMAD can be predicted as a function of the C(exp) following similar correlations to those proposed to common non-volatile excipients, indicating that the nanodroplets of water dispersed in the propellant behave similarly to molecularly solubilized compounds. Cytotoxicity studies of PO(22)EO(14)PO(22) were performed in A549 cells, an alveolar type II epithelial cell line, and indicate that, within the concentration range of interest, the surfactant in question decreases cell viability only lightly. The relevance of this work stems from the fact that aqueous-based HFA-pMDIs are expected to be versatile formulations, with the ability to carry a range of medically relevant hydrophilic compounds within the nanocontainers, including high potency drugs, drug combinations and biomacromolecules. PMID- 22044540 TI - Long-circulating non-toxic blood pool imaging agent based on hyperbranched polyglycerols. AB - PURPOSE: Currently, in vivo or in vitro(99m)Tc-radiolabelled red blood cells are the standard blood pool imaging agents. Due to risks associated with handling of blood and the problems with the current (99m)Tc shortage, we were interested in a long-circulating biocompatible synthetic macromolecule that would be simple to prepare and could also be used for PET imaging. METHODS: A high molecular weight hyperbranched polyglycerol (HPG) of 500 kDa was derivatized to coordinate radioactive gallium and to establish its labelling efficiency, stability and pharmacokinetics. RESULTS: The resulting radiopharmaceutical in kit form was labelled rapidly within a couple of minutes at room temperature, was stable in transferrin and EDTA challenge tests, and was non-toxic in both cell viability and different hemocompatibility assays. A pharmacokinetic biodistribution study showed that the (67)Ga-HPGN was confined to the blood compartment with a biological half life of 50.7h. CONCLUSION: (67)Ga-HPGN is thus a simple to prepare blood pool imaging agent for applications where a long biological half life is essential, i.e., the diagnosis of internal bleeding. Since radiolabelling of the same kit with (68)Ga was also confirmed, we plan to evaluate it shortly as a PET blood pool imaging agent for cardiac applications. PMID- 22044542 TI - [Constipation in cancer patients. Evidence for nursing interventions and promotion of physical activity]. AB - Constipation is one of the most frequent problems in cancer patients. Preventing and managing this problem requires tests to prove the efficacy of the method. The aim of this study was to identify the evidence for nursing intervention aimed at promoting physical activity. The author consulted various databases ((PubMed, CINAHL, Cochrane Library) in July 2010, to identify studies regarding physical exercise and evacuation and found that, although physical activity is considered useful for preventing stipsis, only a few randomized studied sustain this theory. Current nursing practice is based on the opinion of experts regarding the need to encourage physical activity. PMID- 22044541 TI - Molecular characterization of the newly identified human parvovirus 4 in the family Parvoviridae. AB - Human parvovirus 4 (PARV4) is an emerging human virus, and little is known about the molecular aspects of PARV4 apart from its incomplete genome sequence, which lacks information of the termini. We analyzed the gene expression profile of PARV4 using a nearly full-length HPV4 genome in a replication competent system in 293 cells. We found that PARV4 utilizes two promoters to transcribe non structural protein- and structural protein-encoding mRNAs, respectively, which were polyadenylated at the right end of the genome. Three major proteins, including the large non-structural protein NS1a, whose mRNA is spliced, and capsid proteins VP1 and VP2, were detected. Additional functional analysis of the NS1a revealed its capability to induce cell cycle arrest at G2/M phase in ex vivo generated human hematopoietic stem cells. Taken together, our characterization of the molecular features of PARV4 suggests that PARV4 represents a new genus in the family Parvoviridae. PMID- 22044543 TI - [The experience of the Root Cause Analysis (RCA) regarding the adverse event "missing sample from the patient source"]. AB - Creation of the Root Cause Analysis (RCA) represents a phase of clinical risk management and is the instrument chosen for reactive analysis of adverse events. It is important to consider RCA in the context of the entire clinical risk management process and to understand the interrelationships with the previous and subsequent phases, in order to identify the necessary input and the expected output of such activity. In this study the input consisted of the adverse event which occurred after a health worker had been exposed to a biological risk and the "source patient sample" could not be found. The hospital and nursing authorities analyzed the event to understand its dynamics and causes. The results, or output, obtained indicate the steps necessary to go on to the next phase, namely treatment of the risk and the need for systemic measures: improvement of communication , revision of hospital procedures for managing blood samples and modification of the laboratory computer programs. PMID- 22044544 TI - [Aggressive behavior toward nursing staff in three different health care settings. [corrected]. AB - INTRODUCTION: Health providers, particularly nurses, are at high risk for aggression in the workplace. This phenomenon, constantly increasing, it can undermine the resilience of the health providers, increasing the burn-out and staff turnover. AIM: Highlight the frequency and characteristics of violence in different health areas. MATERIALS AND METHODS: A questionnaire, the "Violent Incident Form" (VIF), was administered to 987 nurses belonging to various hospitals and emergency services of Modena. The data, divided into three groups related to health areas of origin, the emergency department, medical-surgical and psychiatric wards, grouped by risk of such violence and work characteristics, were compared with each other. RESULTS: 74% of respondents have suffered at least one episode of violence in the last 3 years, with the highest percentage in psychiatric area (84%). In the general hospital (64%) and in the emergency department (54%), violence was mostly verbal, acted out by patients and by members of their family, while, in psychiatric wards, has been frequently physical (40%) or physical and verbal (33%), made especially from patients with the highest number of physical consequences, never reported to the Court. Only 31% of nurses expected the attack. CONCLUSIONS: This study confirms, in accordance with the literature, that the aggression toward the nurses are a remarkable phenomenon, and it suggests that, to prevent such a violence, are necessary not only precautions and a structural organization, specific for the different health areas, but above all, great awareness and preparation from the health providers around this risk. PMID- 22044545 TI - [Encouragement and protection of breast-feeding: conoscitive study]. AB - The factors associated with exclusive breast-feeding in a Naples health district were studied in October 2008 in the period between the first and second vaccinations (neonates aged between 60 and 120 days) . Questions regarded both the mother and the child and the answers were collected in a database and compared with other methods of nutrition or mixed methods. Statistical analysis was performed using multivariate logistic regression. Results showed that only 38.5% of the mothers interviewed practiced breast-feeding alone while 20% did mixed feeding and 41.5% preferred artificial feeding. The variables negatively related to breast-feeding were: breast problems, older-aged mothers, Cesarean section, first experience of breast-feeding, lack of rooming-in and/or prenatal preparative courses. Positively associated variables were: higher level of education of the mother, higher level of information regarding the advantages of breast-feeding. The conclusions of this study confirm those of previous studies regarding the relationship between exclusive breast-feeding and biological and social factors. PMID- 22044546 TI - [Perioperative nursing education and client satisfaction: an observational study]. AB - Nowadays, an important goal has been reached in recognizing that the client plays a central role in the caring process. The educational relationship that is created between nurses and patients makes it possible to make the patient aware of his health problems and to understand and actively participate in the caring process. The main aim of this study was to assess the effectiveness of the teaching process undertaken by nurses , before discharging surgical patients , for rendering patients autonomous once they returned home and their level of "satisfaction" regarding the information they received. For this purpose they were asked to fill in a questionnaire when they returned for their first outpatient control. Results showed that, on the whole, patients were satisfied with the information they received during hospitalization, particularly in terms of postoperative pain, prevention of infections, medical therapy, mobilization and a return to normal eating and drinking. Some aspects still need to be improved regarding a post-discharge phone contact and better hospital-territorial integration. PMID- 22044547 TI - [The impact of the computerized unique therapeutic card (Computer Assisted Drug Therapy) in a cardiac care setting]. AB - BACKGROUND: The introduction of a unique therapeutic card represents a valid tool for the containment of adverse events during the treatment process, from prescribing a drug to its administration. AIMS: This article aims to illustrate the development and implementation (through the application of the Deming Cycle) of a computerized STU in a cardiac care setting referring to a Department of Cardiology. MATERIALS AND METHODS: A multi-professional team was formed and carried out the following steps: a) analysis of existing clinical documentation highlighting the most critical points with respect to the therapeutic pharmacological process; b) construction of a computerized STU c) sharing information with every member of the professional group involved, d) implementation of the STU in order to assess the areas of improvement. RESULTS: At the end of this procedure, the critical areas evidenced were shown to be markedly improved due to the elimination of errors relating to lack of legibility of handwriting (improvement of 71%, chi2 = 102.589, p <5%), dose and drug which should be administered (improvement of 29%; chi2 = 42.832, p <5%). Furthermore, there is an alignment between the data contained in both medical and nursing records (improvement of 26%, chi2 = 110.589, p <5%) and a complete identification of the subjects / actors in all stages of the process (improvement of 38%, chi2 = 32.284, p <5%). CONCLUSIONS: The survey has documented the significant benefits of the computerized STU in accordance with prior experience and in line with the continuous improvement process of quality of care which is still ongoing. PMID- 22044548 TI - Effectiveness of the telephonic-case-management for treatment of headache. A pilot study. AB - Chronic or intermittent headache affects the patients' quality of life, and has direct and indirect social costs. Several chronic illnesses are already treated through telephone counseling, however there is poor evidence in literature about headache treatment via telenursing, and it is not clear which role could the nurse play in this specific field. The study was carried out at the headache centre of "G. D'Annunzio" University - Chieti, and involved 62 patients, half of them were assigned to receive specialized telenursing in addiction to the standard care bean. During the 13 weeks of follow up the headache characteristics were regularly assessed (frequency and intensity). Pain assessment was performed using the VAS, and quality of life was assessed at baseline and at the end of the follow up using the SF-12 standard V1 questionnaire. The differences between the two groups are statistically significant during the last 5 week of follow up, (8th -12th; 0.002=5.7 cm, whereas increased LVIDD value was detected in only one patient in the other two control groups. There was a significant difference in terms of the presence of increased LVIDD values between the MVP group and the control groups. Despite this enlargement in the LV dimension, the LV ejection fractions were found similar in all groups. Furthermore, it was found that the lengths of both anterior and posterior mitral leaflets in MVP group were significantly higher than those in the control groups. CONCLUSION: The LV diameters and volumes of patients with classic bileaflet MVP were found to be increased even in the absence of significant MR. These results need to be supported by large-scale clinical studies. PMID- 22044563 TI - Insulin-like growth factor receptor expression is associated with aggressive phenotypes and has therapeutic activity in biliary tract cancers. AB - Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling is required for carcinogenicity and progression of several cancers but the function of this pathway and its utility as a therapeutic target have not been studied comprehensively in biliary tract carcinomas (BTC). We investigated the immunohistochemical expression of elements of the IGF axis, matrilysin, overexpression of p53 and the methylation status of the IGFBP-3 promoter in 80 surgically resected BTC. We also assessed the effect of IGF-IR blockade on signal transduction, proliferation and survival in three BTC cell lines using a new tyrosine kinase inhibitor, BMS-536924, and dominant negative IGF-IR (IGF-IR/dn). The effects of IGF-IR blockade was also studied in nude mouse xenograft models. IGF-I was expressed in 60% and IGF-II in 50% of tumors. High expression was associated with tumor size. IGF-IR was expressed in 69% of the cases and was associated with advanced stage and matrilysin expression. Hypermethylation of the IGFBP-3 promoter was detected in 41% of BTC and was inversely correlated with p53 expression. BMS-536924 blocked autophosphorylation of IGF-IR and both Akt and ERK activation by both IGF-I and insulin. BMS-536924 suppressed proliferation and tumorigenicity in vitro in a dose-dependent fashion. This inhibitor upregulated chemotherapy-induced apoptosis in a dose-dependent fashion. Moreover, IGF-IR blockade was effective against tumors in mice. IGF-IR might identify a subset of BTC with a particularly aggressive phenotype and is a candidate therapeutic target in this disease. BMS-536924 might have significant therapeutic utility. PMID- 22044564 TI - Technical standardization of laparoscopic direct hernia repair in pediatric patients. AB - BACKGROUND: The aim of this article is to standardize the laparoscopic technique to treat direct inguinal hernia in pediatric patients. PATIENTS AND METHODS: In the last 3 years we treated laparoscopically 163 patients with a diagnosis of inguinal hernia. In 7 patients we discovered laparoscopically a direct inguinal hernia. This study is focused on the management of these 7 cases (4 girls and 3 boys; median age 4.6 years). They presented a right defect in 4 cases and a left defect in 3 cases. Six of 7 patients had been already operated for an inguinal hernia and presented a recurrence of the hernia. We used three trocars, 5-mm 0 degree optic, and two 3-mm instruments. In each case, after the resection of the lipoma using the hook cautery, the defect was closed by means of separated stitches. In every case we used the vesical ligament as an autologous patch to reinforce the closure of the defect. RESULTS: The average operative time was 35 minutes. All the procedures were performed in a day-hospital setting. We had neither conversions nor complications in our series. With a minimum follow-up of 1 year, we had no recurrence. CONCLUSIONS: Laparoscopic identification and repair of direct inguinal hernia in children is a safe and effective procedure to adopt. The key points of the technique are the resection of the lipoma, the closure of the defect using separated, nonabsorbable sutures, and the use of the vesical ligament to reinforce the suture. We believe that in case of recurrence of inguinal hernias after inguinal approach, laparoscopy is the gold standard technique to identify and treat the cause of the recurrence itself. PMID- 22044565 TI - Endoscopic thyroidectomy: the development in a Chinese center. AB - BACKGROUND: Endoscopic thyroidectomy (ET) precludes the long cervical incision of the open procedure. Although endoscopy is an essential tool taught to almost every surgeon, its effective use with regard to thyroidectomy requires understanding its limitations pertaining to trauma and cancer, as well as an understanding of the advantages and disadvantages of the different endoscopic approaches. The development of an ET center in China is discussed here. METHODS: Overall, 235 patients who had undergone attempted ET in Qilu Hospital of Shandong University in China from August 2001 to September 2010 were evaluated. RESULTS: Of the 11 men and 224 women on whom the procedure had been attempted, all but seven successfully underwent ET, 145 (63.6%) via a modified anterior chest approach, and 83 (36.4%) via a breast approach. Age ranged from 17 to 52 years, with a mean of 34.5 years. Surgery was limited, in the case of masses, to lesions smaller than 6 cm ultrasonographically. All patients were followed for at least 3 months. The 24 and 48 hours Visual Analog Scale postoperative measurements were low. Complications included four cases of cutaneous emphysema, five seromas, four episodes of anterior chest discomfort, three transient laryngeal nerve palsies, and four episodes of hypocalcemia. The seven procedures that had been converted to an open procedure comprised two patients discovered at frozen section to have poorly differentiated thyroid carcinoma, two with tumors larger than 5 cm, and three with thyroiditis. CONCLUSIONS: ET is readily learned, provided the surgeon is competent at both laparoscopic technique and open thyroidectomy. Procedural advantages of an endoscopic approach include superior cosmesis and decreased invasiveness. PMID- 22044566 TI - Ready or not--here we go into our future!!! PMID- 22044567 TI - Fathers' perceptions of their roles during in-home training for children with autism. AB - PROBLEM: Currently, most research related to parents of children with autism has focused on mothers, and little is known about the fathers' interaction with their children. PURPOSE: The purpose of the qualitative study is to assist in more fully describing and understanding fathers' perceptions of their roles, relationships with their children with autism, and participation in an in-home training intervention designed to enhance parent-child interactions as well as child language and social interactions. METHODS: In depth semi-structured interviews with 10 fathers were conducted at home, videotaped, transcribed, and reviewed for common themes and significant statements FINDINGS: Five common themes were discovered, fathers expressed their view of their roles, and fathers reported the father-directed in-home intervention was effective in enhancing father-child relationships. CONCLUSION: Communication between fathers and their children appears to be the key to a successful relationship. Although verbal communication deficit is a predominant feature of autism, these fathers noted other ways of effective communicating including time spent playing or just being with the child. PMID- 22044568 TI - A relationship-based intervention to improve social connectedness in street involved youth: a pilot study. AB - PROBLEM: Street-involved youth experience a range of mental health problems with elevated rates of psychiatric disorders compared with non-homeless youth. The overall objective of this pilot study was to evaluate the impact of a relationship-based intervention for homeless youth receiving services from agencies in downtown Toronto. METHODS: The final sample included 15 homeless youth who met the study inclusion criteria. The intervention and comparison groups were compared at baseline and post-treatment on measures of mental health symptoms, hopelessness, self-esteem, resilience, and social connectedness. FINDINGS: Participants receiving the intervention demonstrated a significant improvement in social connectedness, with a trend toward decreased hopelessness. Those participants who did not receive the intervention did not demonstrate any improvements in social connectedness and hopelessness. CONCLUSION: This preliminary pilot study suggests that providing a relationship-based intervention to street-involved youth may offer promise to strengthen social relationships and to mitigate overwhelming hopelessness and despair. PMID- 22044569 TI - Hopefulness among non-U.S.-born Latino youth and young adults. AB - PROBLEM: U.S. Latino youths experience disproportionately high rates of health and social problems. There is a need to identify protective factors for reducing risky behaviors. Little is known about the protective nature of hope among immigrant Latino adolescents. METHODS: This descriptive cross-sectional study examined hope and expectations for the future in non-U.S.-born Latino adolescents and young adults (n= 98) in urban and rural areas in the midwestern United States. FINDINGS: Participants reported feeling hopeful about their future; however, differences were detected among subgroups. CONCLUSION: Findings affirm the potential of hope as a protective factor for immigrant Latino adolescents and young adults. Nurses should be aware of hopefulness when implementing mental health preventive interventions. Research is needed to identify effective mechanisms for promoting and sustaining hope. PMID- 22044570 TI - Consequences of intimate partner violence on child witnesses: a systematic review of the literature. AB - PROBLEM: Intimate partner violence (IPV) is a serious social problem that affects all members of a household. Approximately 22% of violent crimes perpetrated against women and 3% against men are related to IPV, and often children witness these crimes. This paper addresses the evidence related to the short- and long term consequences on the physical, psychosocial, and emotional status of child witnesses. METHODS: A systemic review and analysis of the literature was performed with 24 articles from 2000 to 2010 that were identified through electronic search strategies. FINDINGS: Differences were found in the behaviors of children who witness and do not witness IPV that have short- and long-term consequences and affect relationships with same-sex peers, dating partners, and future partners with a clear pattern of dose-response. CONCLUSIONS: Healthcare providers can implement theoretically driven, gender and culturally appropriate interventions for children with a history of IPV exposure with outcomes that positively affect the lives of children. PMID- 22044571 TI - Suicidal thought in the adolescent: exploring the relationship between known risk factors and the presence of suicidal thought. AB - PROBLEM: The purpose of this retrospective study was to explore the relationship between recognized risk factors for suicidal thought and the presence or absence of self-reported suicidal thought. METHODS: This study was conducted through the secondary analysis of data obtained from a larger, prospective, cluster randomized intervention study. A subset of 817 recruits between the ages of 17 and 19 was included in this study. FINDINGS: A personal history of mental health/emotional problems and a decreased sense of belonging made unique contributions to predicting the presence of suicidal thought. CONCLUSIONS: The development of interventions to increase sense of belonging may be a key to reducing suicidal thought during stressful events. PMID- 22044572 TI - Young people's preferences for emotional well-being support in high school--a focus group study. AB - PROBLEM: Schools have been identified as a suitable setting for the delivery of emotional well-being (EWB) support, but in the United Kingdom there is little empirical evidence from young people that can inform the development of appropriate school-based interventions. METHODS: Fifty-four students (11-16 years) from three U.K. high schools discussed the content, delivery, and evaluation of acceptable, school-based, EWB support. Focus group methods were matched to the school setting and sensitive topic. FINDINGS: Participants identified emotional difficulties in school, home, and with peer relationships. They said that some problems were too sensitive for them to seek help in school setting. They valued confidentiality, support, and effective help that were offered by people they experienced as friendly, trustworthy, and skilled. Teachers and peer mentors were not thought to fit these criteria, although trusted adults in mentor roles could meet their criteria. Participants recognized that they could hide their emotions, so their EWB would be difficult to assess. They described how the effect of emotional distress on their behavior is idiosyncratic, and therefore their EWB should not be judged simply on their behavior. CONCLUSION: The way in which EWB support is delivered in school is an important aspect of the role of practitioners and educators attempting to provide it. Because young people are sensitive to the personal qualities and skills of people offering them help, programs to train school staff in emotional support roles are important to ensure trust and an environment open to students seeking assistance. Interventions for school-based EWB support need to consider subjective well-being as well as behavioral change. PMID- 22044574 TI - Genetic eye research in Tasmania: a historical overview. AB - Although considerable recent work on hereditary eye diseases in Tasmanian families has been published, much of this depended on a century of meticulous pedigree collection by earlier clinical researchers. This article reviews some of the historical papers and the importance they have played in gene discovery and understanding of ophthalmic genetics. Tasmanian families have contributed to the identification of genes for X-linked megalocornea, Leber's hereditary optic neuropathy, retinitis pigmentosa, congenital cataract, ptosis, keratoconus, glaucoma and myopia. The true value of the Tasmanian pedigrees will be realized with the translation of genetic discoveries into early diagnosis and treatment for these eye diseases. PMID- 22044576 TI - Primary pulmonary hypertension, congenital heart defect, central nervous system malformations, hypo- and aplastic toes: another case of Yunis-Varon syndrome or report of a new entity. AB - Here we describe a patient with a new malformation syndrome which shows similarities with Yunis-Varon syndrome (YVS). Prenatal presentation included polyhydramnios, increased nuchal translucency, and bilateral hydrothoraces requiring pigtail insertion. Postnatal presentation revealed primary pulmonary hypertension (PPH), persistent hydrothoraces, one atrial and two ventricular septal defects, hypoplasia of the corpus callosum and cerebellar vermis, dilated interhemispheric ventricles, severe developmental delay with general muscular hypotonia, retinal anomalies, sparse scalp hair, sparse eyebrows and eyelashes, hypo- and aplastic nails, low-set dysplastic ears, loose nuchal skin, hypo- and aplastic distal phalanges of the toes as well as postnatal failure to thrive. High resolution molecular karyotyping in the patient did not reveal any causative chromosomal aberration. Since one patient with YVS and PPH has been previously reported, we assume a similar pathogenic pathway. However, molecular confirmation of the clinical diagnosis is not yet possible. It remains uncertain if the presented syndrome can be classified as YVS with PPH or if it constitutes a new YVS like entity. PMID- 22044575 TI - Neutrophil extracellular traps promote deep vein thrombosis in mice. AB - BACKGROUND: Upon activation, neutrophils can release nuclear material known as neutrophil extracellular traps (NETs), which were initially described as a part of antimicrobial defense. Extracellular chromatin was recently reported to be prothrombotic in vitro and to accumulate in plasma and thrombi of baboons with experimental deep vein thrombosis (DVT). OBJECTIVE: To explore the source and role of extracellular chromatin in DVT. METHODS: We used an established murine model of DVT induced by flow restriction (stenosis) in the inferior vena cava (IVC). RESULTS: We demonstrate that the levels of extracellular DNA increase in plasma after 6 h IVC stenosis, compared with sham-operated mice. Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated histone H3 (CitH3), an element of NETs' structure, was present only in the red part of thrombi and was frequently associated with the Gr-1 antigen. Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated mixture of calf thymus histones increased plasma VWF and promoted DVT early after stenosis application. CONCLUSIONS: Extracellular chromatin, likely originating from neutrophils, is a structural part of a venous thrombus and both the DNA scaffold and histones appear to contribute to the pathogenesis of DVT in mice. NETs may provide new targets for DVT drug development. PMID- 22044577 TI - General practitioners' views and experiences of counselling for physical activity through the New Zealand Green Prescription program. AB - BACKGROUND: Regular physical activity is beneficial in both the prevention and management of chronic health conditions. A large proportion of adult New Zealanders, however, are insufficiently active. To help increase population levels of physical activity in New Zealand the Green Prescription, a primary care physical activity scripting program, was developed. The primary aim of this study was to identify why general practitioners (GPs) counsel for physical activity and administer Green Prescriptions. A secondary aim was to examine GPs' views and experiences of Green Prescription counselling for the management of depression. METHODS: Individual face-to-face interviews were conducted with 15 GPs. All interviews were audio-taped and transcribed. Data were analysed using an inductive thematic approach. RESULTS: Several themes and sub-themes emerged from the data. Notably, GPs counselled for physical activity and prescribed Green Prescriptions for both primary preventive (e.g., weight control) and secondary management (e.g., diabetes management) purposes. GPs reported the benefits of the Green Prescription centred around two main themes: (i) a non-medication approach to a healthier lifestyle and (ii) the support benefits of physical activity. Time constraints within the consultation was the only main theme that emerged regarding the barriers GPs perceived to Green Prescription use. Physical activity in general, and physical activity prescribed through the Green Prescription, were also viewed by GPs as beneficial for the management of depression. CONCLUSIONS: The results of this study suggest that New Zealand GPs view the Green Prescription program as beneficial for their patients with pre-existing conditions and/or weight problems. While this is encouraging, the Green Prescription may also be used to promote physical activity in currently healthy but low-active and sedentary individuals. Such individuals are currently disease free, but are at risk for future health-related problems because of their inactive lifestyle. It is recommended that time constraints of the consultation in regard to administering Green Prescriptions could be dealt with by delegating the more time consuming tasks to the patient support counsellors that support the Green Prescription program, and having practice nurses assist in the administration of Green Prescriptions. Green Prescription counselling in conjunction with antidepressant medication may be beneficial for the management of depression and warrants further research. PMID- 22044578 TI - Immunomodulatory properties of Xylaria nigripes in peritoneal macrophage cells of Balb/c mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Wu Ling Shen, a folklore name for Xylaria nigripes (XN), is a high value medicinal fungus used in traditional Chinese medicine. AIM OF STUDY: The present study aimed to examine the immunomodulatory properties of aqueous (XN-H) and ethanol (XN-E) XN extracts in lipopolysaccharide (LPS)-induced peritoneal macrophage cells of Balb/c mice. MATERIALS AND METHODS: After treating the macrophage cells with LPS (1 MUg/ml) and different XN extracts, the immunomodulatory properties were determined by the responses of inflammatory mediators, namely nitrite oxide (NO), prostaglandin E2 (PGE(2)) and cytokine (IL-1beta, IL-6, TNF-alpha and IFN-gamma) production, iNOS, COX-2 and IkappaB-alpha expression, and NF-kappaB activation. RESULTS: Results showed that treatment of macrophages with 5-30 MUg/ml of XN-H or XN-E plus 1 MUg/ml LPS exhibited no cytotoxic effect on cell viability. At these concentrations, although both XN-H and XN-E showed a dose-dependent inhibitory effect on NO, PGE(2), IL-1beta, IL-6, TNF-alpha and IFN-gamma production in LPS-stimulated macrophages, a greater potency was noted in the XN-H treated group. RT-PCR assay also showed that XN-H possessed a greater inhibition than XN-E on iNOS and COX-2 RNA expression. Furthermore, XN-H also showed a significant stronger suppression than XN-E on the LPS-induced IkappaB-alpha phosphorylation and NF-kappaB activation. XN-E showed a higher total flavonoid and phenol contents but a lower beta-glucan content than XN-H. CONCLUSION: Taken together, these results conclude that XN-H possesses a stronger anti-inflammatory activity than XN-E, and its mechanism of action could be mediated by inhibiting iNOS and COX-2 expression via the NF-kappaB signaling pathway, and these activities could be contributed by the beta-glucan content. PMID- 22044579 TI - Diagnosis and management of anaemia and iron deficiency in patients with haematological malignancies or solid tumours in France in 2009-2010: the AnemOnHe study. AB - OBJECTIVE: To describe the management of anaemia in 2009-2010 in France in patients with haematological malignancies (HM) or solid tumours (ST). METHODS: Retrospective observational study in 57 centres, enrolling adult patients with HM or ST treated for an episode of anaemia (duration of the episode >= 3 months occurring in the last 12 months). RESULTS: 220 patients with ST (breast, 18%; lung, 18%) and 56 with HM (lymphoma, 60%) were included (median age, 68 years; female, 53%). Mean haemoglobin level at anaemia diagnosis was 9.3 +/- 1.4 g/dL (<8 g/dL for 16%) and 9.8 +/- 1.1g/dL (<8 g/dL for 6%) in HM and ST patients, respectively. At least one parameter of iron deficiency (ferritin, transferrin saturation) was assessed in 26% of HM and 19% of ST patients. Treatment of anaemia included erythropoiesis-stimulating agents (ESA) for 98% of HM and 89% of ST patients. Iron was prescribed to 14% (oral, 12%; intravenous, 2%) of HM patients and to 42% (oral, 17%; intravenous, 25%) of ST patients. The rates of blood transfusions were high: 70% in HM and 46% in ST patients; transfusions alone or administrated with ESA were more frequent in patients with Hb <8 g/dL. CONCLUSION: Although recent guidelines recommend evaluating iron deficiency and correcting anaemia by using intravenous iron, our study in cancer patients evidenced that ESA and blood transfusions are still frequently used as the treatment of anaemia in cancer patients. Iron deficiency is insufficiently assessed (only one patient among five) and as a consequence iron deficiency is most likely insufficiently treated. PMID- 22044580 TI - A giant plexiform schwannoma of the brachial plexus: case report. AB - We report the case of a patient who noticed muscle weakness in his left arm 5 years earlier. On examination, a biloculate mass was observed in the left supraclavicular area, and Tinel's sign caused paresthesia in his left arm. Magnetic resonance imaging showed a continuous, multinodular, plexiform tumor from the left C5 to C7 nerve root along the course of the brachial plexus to the left brachia. Tumor excision was attempted. The median and musculocutaneous nerves were extremely enlarged by the tumor, which was approximately 40 cm in length, and showed no response to electric stimulation. We resected a part of the musculocutaneous nerve for biopsy and performed latissimus dorsi muscle transposition in order to repair elbow flexion. Morphologically, the tumor consisted of typical Antoni A areas, and immunohistochemistry revealed a Schwann cell origin of the tumor cells moreover, there was no sign of axon differentiation in the tumor. Therefore, the final diagnosis of plexiform Schwannoma was confirmed. PMID- 22044581 TI - A Bayesian model for gene family evolution. AB - BACKGROUND: A birth and death process is frequently used for modeling the size of a gene family that may vary along the branches of a phylogenetic tree. Under the birth and death model, maximum likelihood methods have been developed to estimate the birth and death rate and the sizes of ancient gene families (numbers of gene copies at the internodes of the phylogenetic tree). This paper aims to provide a Bayesian approach for estimating parameters in the birth and death model. RESULTS: We develop a Bayesian approach for estimating the birth and death rate and other parameters in the birth and death model. In addition, a Bayesian hypothesis test is developed to identify the gene families that are unlikely under the birth and death process. Simulation results suggest that the Bayesian estimate is more accurate than the maximum likelihood estimate of the birth and death rate. The Bayesian approach was applied to a real dataset of 3517 gene families across genomes of five yeast species. The results indicate that the Bayesian model assuming a constant birth and death rate among branches of the phylogenetic tree cannot adequately explain the observed pattern of the sizes of gene families across species. The yeast dataset was thus analyzed with a Bayesian heterogeneous rate model that allows the birth and death rate to vary among the branches of the tree. The unlikely gene families identified by the Bayesian heterogeneous rate model are different from those given by the maximum likelihood method. CONCLUSIONS: Compared to the maximum likelihood method, the Bayesian approach can produce more accurate estimates of the parameters in the birth and death model. In addition, the Bayesian hypothesis test is able to identify unlikely gene families based on Bayesian posterior p-values. As a powerful statistical technique, the Bayesian approach can effectively extract information from gene family data and thereby provide useful information regarding the evolutionary process of gene families across genomes. PMID- 22044582 TI - Quantifying the environmental impact of As and Cr in stabilized/solidified materials. AB - The assessment of the quality of sediment from the Great Backi Canal (Serbia) based on the pseudo-total As and Cr content according to the corresponding Dutch standards and Canadian guidelines showed its severe contamination with these two elements. Microwave assisted BCR sequential extraction procedure was employed to assess their potential mobility and risk to the aquatic environment. Comparison of the results of sequential extraction and different criteria for sediment quality assessment has led to somewhat contradictory conclusions. While the results of sequential extraction showed that Cr comes under the medium risk category, As shows no risk to the environment, despite of its high pseudo-total content. The contaminated sediment, irrespective of the different distribution of As and Cr, was subjected to the same immobilization, stabilization/solidification (S/S) treatment. Semi-dynamic leaching test was conducted for As and Cr contaminated sediment in order to assess the long-term leaching behavior of these elements. In order to simulate "worst case" leaching conditions, the test was modified using acetic acid and humic acid solution as leachants instead of deionized water. The effectiveness of S/S treatment was evaluated by determining diffusion coefficients. Four different single-step leaching tests were applied to evaluate the extraction potential of As and Cr. A diffusion-based model was used to elucidate the controlling leaching mechanisms. The test results indicated that all applied S/S treatments were effective in immobilizing As and Cr, irrespective of their different availabilities in the untreated samples. In most treated samples, the controlling leaching mechanism appeared to be diffusion, which indicates that a slow leaching of As and Cr could be expected. PMID- 22044583 TI - Influence of source distribution and geochemical composition of aerosols on children exposure in the large polymetallic mining region of the Bolivian Altiplano. AB - The Bolivian Altiplano (Highlands) region is subject to intense mining, tailing and smelting activities since centuries because of the presence of large and unique polymetallic ore deposits (Ag, Au, Cu, Pb, Sn, Sb, Zn). A large scale PM(10), PM(2.5) aerosol monitoring survey was conducted during the dry season in one of the largest mining cities of this region (Oruro, 200,000 inhabitants). Aerosol fractions, source distribution and transport were investigated for 23 elements at approximately 1 km(2) scale resolution, and compared to children exposure data obtained within the same geographical space. As, Cd, Pb, Sb, W and Zn in aerosols are present at relatively high concentrations when compared to studies from other mining regions. Arsenic exceeds the European council PM(10) guide value (6 ng/m(3)) for 90% of the samples, topping 200 ng/m(3). Ag, As, Cd, Cu, Pb and Sb are present at significantly higher levels in the district located in the vicinity of the smelter zone. At the city level, principal component analysis combined with the mapping of factor scores allowed the identification and deconvolution of four individual sources: i) a natural magmatic source (Co, Cs, Fe, K, Mn, Na, Rb and U) originating from soil dust, resuspended by the traffic activity; ii) a natural sedimentary source (Mg, Ca, Sr, Ba and Th) resulting from the suspension of evaporative salt deposits located South; iii) an anthropogenic source specifically enriched in mined elements (As, Cd, Cu, Pb, Sb and Zn) mainly in the smelting district of the city; and iv) a Ni-Cr source homogenously distributed between the different city districts. Enrichment factors for As, Cd and Sb clearly show the impact of smelting activities, particularly in the finest PM(2.5) fraction. Comparison to children's hair metal contents collected in five schools from different districts shows a direct exposure to smelting activity fingerprinted by a unique trace elements pattern (Ag, As, Cu, Pb, Sb). PMID- 22044584 TI - Continuous administration of poloxamer 188 reduces overload-induced muscular atrophy in dysferlin-deficient SJL mice. AB - Dysferlin-deficient SJL mice are commonly used to study dysferlinopathy. We demonstrated that poloxamer 188 (P188), a membrane sealant, is effective in reducing the loss of muscle mass in SJL mice when administered using an osmotic pump for 6 weeks. We did not observe significant changes over a 2-week administration period, suggesting that longthier observation is necessary to determine the effectiveness of P188. We also examined exercise endurance in P188 administered SJL mice using a rolling cage. Phosphorylated p38 was found to be reduced in P188-administered SJL mice; additionally, using microarray analysis, we found diminished expression of atrogin-1, an E3 ubiquitin ligase, as the effector of muscular atrophy. Chronic infusion of P188 to dysferlin-deficient SJL mice reduced muscular atrophy, and administering p38 and atrogin-1 in the gastrocnemius muscle improved its motor function. These results provide a basis for potential treatments for dysferlin-deficient skeletal muscle fibers. PMID- 22044585 TI - Endurance exercise modifies the circadian clock in zebrafish (Danio rerio) temperature independently. AB - AIM: Several rodent and human studies revealed that physical exercise acts as a non-photic zeitgeber for the circadian clock. The intrinsic entraining mechanism is still unknown, although it was assumed that the exercise-mediated increase in core temperature could be the underlying zeitgeber. As the homoeostatic control of mammalian core temperature interferes strongly with the investigation of this hypothesis, the present study used the poikilotherm zebrafish to answer this question. METHODS: Gene transcription levels of the two circadian core clock genes period1 and clock1 were quantified using real-time qPCR of whole animal zebrafish larvae. RESULTS: Long-term endurance exercise of zebrafish larvae aged 9-15 days post-fertilization (dpf) or 21-32 dpf at a constant water temperature of 25 degrees C caused significantly altered transcription levels of the circadian genes period1 and clock1. Cosinor analysis of diurnal transcription profiles obtained after 3 days of swim training revealed significant differences regarding acrophase, mesor and amplitude of period1, resulting in a phase delay of the gene oscillation. After termination of the exercise bout, at 15 dpf, oscillation amplitudes of both circadian genes were significantly reduced. CONCLUSION: The results showed that physical exercise is able to affect the transcription of circadian genes in developing zebrafish larvae. Considering the poikilothermy of zebrafish, an exercise-mediated change in body core temperature could be excluded as the underlying intrinsic zeitgeber. However, the day-active zebrafish arises as a useful model to address the synchronizing effect of exercise on the circadian clock. PMID- 22044586 TI - Effects of inclusion on the academic achievement and adaptive behaviour of children with intellectual disabilities. AB - BACKGROUND: While an extensive body of research has examined the outcomes of inclusion for pupils with special needs, in particular learning disabilities, its effects on the development of children with intellectual disabilities (ID) have been less explored. As inclusive practices tend to be more common for this group of children, it is important to acquire more knowledge on this issue. METHODS: A comparative study with an experimental group of 34 children with ID fully included in general education classrooms with support, and a control group of 34 comparable children in special schools has been conducted. The progress accomplished by these two groups in their academic achievement and adaptive behaviour has been compared over two school years. RESULTS: Included children made slightly more progress in literacy skills than children attending special schools. No differences were found between the progress of the two groups in mathematics and adaptive behaviour. CONCLUSIONS: Inclusive education is an appropriate educational option for primary pupils with ID who require extensive support in school. PMID- 22044588 TI - p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia. AB - Inhibition of tumor suppressor p53 is cardioprotective against ischemic injury and provides resistance to subsequent cardiac remodeling. We investigated p53 mediated expansion of ischemic damage with a focus on mitochondrial integrity in association with autophagy and apoptosis. p53(-/-) heart showed that autophagic flux was promoted under ischemia without a change in cardiac tissue ATP content. Electron micrographs revealed that ischemic border zone in p53(-/-) mice had 5 fold greater numbers of autophagic vacuoles containing mitochondria, indicating the occurrence of mitophagy, with an apparent reduction of abnormal mitochondria compared with those in WT mice. Analysis of autophagic mediators acting downstream of p53 revealed that TIGAR (TP53-induced glycolysis and apoptosis regulator) was exclusively up-regulated in ischemic myocardium. TIGAR(-/-) mice exhibited the promotion of mitophagy followed by decrease of abnormal mitochondria and resistance to ischemic injury, consistent with the phenotype of p53(-/-) mice. In p53(-/-) and TIGAR(-/-) ischemic myocardium, ROS production was elevated and followed by Bnip3 activation which is an initiator of mitophagy. Furthermore, the activation of Bnip3 and mitophagy due to p53/TIGAR inhibition were reversed with antioxidant N-acetyl-cysteine, indicating that this adaptive response requires ROS signal. Inhibition of mitophagy using chloroquine in p53(-/ ) or TIGAR(-/-) mice exacerbated accumulation of damaged mitochondria to the level of wild-type mice and attenuated cardioprotective action. These findings indicate that p53/TIGAR-mediated inhibition of myocyte mitophagy is responsible for impairment of mitochondrial integrity and subsequent apoptosis, the process of which is closely involved in p53-mediated ventricular remodeling after myocardial infarction. PMID- 22044589 TI - Community health service capacity in China: a survey in three municipalities. AB - RATIONALE: China is reforming its health care system. It aims to strengthen primary health care through building community health facilities and assigning a 'gate-keeper' role to primary care providers. However, it remains unknown whether community health facilities are able to fulfil such a mission. This study evaluated the service capacity of a selected sample of community health facilities and the competency of primary care practitioners employed by those facilities. METHODS: Three municipalities from the east, middle and west of China were purposely selected. A questionnaire was undertaken in 45 randomly selected community health facilities in the three municipalities and 700 primary care practitioners responded to the survey. The survey investigated the capacity of the community health facilities in providing diagnostic services and the competency of the primary care providers in handling common health problems. RESULTS: The most common reasons for doctor-patient encounters were common cold and chronic diseases. The capacity of the community health facilities in providing diagnostic services was limited. Although the majority of respondents believed that they could correctly identify common symptoms, many were unable to perform some essential physical examinations. CONCLUSION: The community health facilities are not able to fulfil their designated mission because of the limited diagnostic capacity and poor competency of the primary care practitioners. Priorities should be given to capacity building for the development of community health services in the future. PMID- 22044590 TI - Effects of rehydration nutrients on H2S metabolism and formation of volatile sulfur compounds by the wine yeast VL3. AB - In winemaking, nutrient supplementation is a common practice for optimising fermentation and producing quality wine. Nutritionally suboptimal grape juices are often enriched with nutrients in order to manipulate the production of yeast aroma compounds. Nutrients are also added to active dry yeast (ADY) rehydration media to enhance subsequent fermentation performance. In this study we demonstrate that nutrient supplementation at rehydration also has a significant effect on the formation of volatile sulfur compounds during wine fermentations. The concentration of the 'fruity' aroma compounds, the polyfunctional thiols 3 mercaptohexan-1-ol (3MH) and 3-mercaptohexyl acetate (3MHA), was increased while the concentration of the 'rotten egg' aroma compound, hydrogen sulfide (H2S), was decreased. Nutrient supplementation of the rehydration media also changed the kinetics of H2S production during fermentation by advancing onset of H2S production. Microarray analysis revealed that this was not due to expression changes within the sulfate assimilation pathway, which is known to be a major contributor to H2S production. To gain insight into possible mechanisms responsible for this effect, a component of the rehydration nutrient mix, the tri peptide glutathione (GSH) was added at rehydration and studied for its subsequent effects on H2S formation. GSH was found to be taken up during rehydration and to act as a source for H2S during the following fermentation. These findings represent a potential approach for managing sulfur aroma production through the use of rehydration nutrients. PMID- 22044591 TI - Which patients are at the highest risk of dying from competing causes <= 10 years after radical prostatectomy? AB - Study Type - Outcomes (cohort). Level of Evidence 2b. What's known on the subject? and What does the study add? Several comorbidity classifications have been investigated for their suitability to assist treatment decision-making in men with early prostate cancer. In unselected patients, some serious comorbidities have been shown to be associated with a 10-year competing mortality rate clearly superseding the 50% level. The present study shows that it is hardly possible to discern meaningful subsets of patients with a 10-year risk of competing mortality of >50% by using comorbidity classifications. This finding suggests that the selecting clinicians did well in estimating the medium-term survival probability in men referred for radical prostatectomy. OBJECTIVE: * To identify subsets of patients who are most likely to die from competing causes <= 10 years after radical prostatectomy (RP). PATIENTS AND METHODS: * In all, 2205 consecutive patients who underwent RP for clinically localized prostate cancer between 1992 and 2005 were studied. The 10-year cumulative competing mortality rates were determined in several worst-case scenarios formed by using comorbidity classifications and combinations of them. RESULTS: * In this sample of men selected for RP, even those with the most severe comorbidity level had a competing mortality risk of <50% <= 10 years after RP. * Depending on the comorbidity classification used, the 10-year cumulative competing mortality rates differed between 16 and 39% in the whole sample and between 18 and 48% in men aged >= 65 years. CONCLUSION: * Clinicians do well in estimating the further life span in candidates for RP. Comorbidity classifications may assist treatment choice in this population but are not able to discern meaningful subsets to be excluded from curative treatment because of a life expectancy falling below a limit of 10 years. PMID- 22044592 TI - Cor triatriatum dextro iatrogenica: an unusual complication of atrial septal defect closure device. AB - We present a case of a rare complication of atrial septal defect (ASD) device closure causing cor triatriatum dextro iatrogenica. A 29-year-old female presented with sudden onset dysarthria and ataxia and was found to have basilar and thalamic infarcts. Further evaluation using transthoracic echocardiography revealed an ASD which was repaired using the Gore HELEX septal occluder. Transesophageal echocardiography done after 2 months of ASD closure revealed an interesting finding termed cor triatriatum dextro iatrogenica. We briefly describe the case and discuss the relevant literature. PMID- 22044593 TI - Central nervous system event in patients with diffuse large B-cell lymphoma in the rituximab era. AB - Central nervous system (CNS) events, including CNS relapse and progression to CNS, are known to be serious complications in the clinical course of patients with lymphoma. This study aimed to evaluate the risk of CNS events in patients with diffuse large B-cell lymphoma in the rituximab era. We performed a retrospective survey of Japanese patients diagnosed with diffuse large B-cell lymphoma who underwent primary therapy with R-CHOP chemoimmunotherapy between September 2003 and December 2006. Patients who had received any prophylactic CNS treatment were excluded. Clinical data from 1221 patients were collected from 47 institutions. The median age of patients was 64 years (range, 15-91 years). We noted 82 CNS events (6.7%) and the cumulative 5-year probability of CNS events was 8.4%. Patients with a CNS event demonstrated significantly worse overall survival (P < 0.001). The 2-year overall survival rate after a CNS event was 27.1%. In a multivariate analysis, involvement of breast (relative risk [RR] 10.5), adrenal gland (RR 4.6) and bone (RR 2.0) were identified as independent risk factors for CNS events. We conclude that patients with these risk factors, in addition to patients with testicular involvement in whom CNS prophylaxis has been already justified, are at high risk for CNS events in the rituximab era. The efficacy and manner of CNS prophylaxis in patients for each involvement site should be evaluated further. PMID- 22044594 TI - Extrapyramidal adverse drug reactions associated with trimetazidine: a series of 21 cases. AB - Over the last few years, a number of cases of extrapyramidal disorders associated with trimetazidine (TMZ) use has been reported. Here, we report on a series of 21 cases. All but one of the patients (mean age 74) had been taking TMZ for several years. The indication for prescription of TMZ could not be identified in seven cases. The TMZ-associated adverse drug reactions were typical parkinsonism (akinesia and/or rigidity and/or rest tremor) in 17 cases, gait disorders in three cases (one with orthostatic tremor), and restless leg syndrome in one case. Discontinuation of TMZ led to complete disappearance of the symptoms in 16 cases and a significant reduction in the five other patients. TMZ has the same piperazine core as the dopamine antagonists flunarizine and cinnarizine (both of which have been reported to induce extrapyramidal symptoms). Hence, striatal D2 receptor blockade could result in the onset or the worsening of extrapyramidal disorders. Even though this adverse drug reaction is now listed in TMZ's Summary of Product Characteristics (because of the initial reports), the risk remains poorly known by clinicians. There is a need to raise awareness of this phenomenon and to reassess TMZ 's risk-benefit ration, especially in the elderly. PMID- 22044595 TI - Use of CNS medications and cognitive decline in the aged: a longitudinal population-based study. AB - BACKGROUND: Previous studies have found associations between the use of central nervous system medication and the risk of cognitive decline in the aged. Our aim was to assess whether the use of a single central nervous system (CNS) medication and, on the other hand, the combined use of multiple CNS medications over time are related to the risk of cognitive decline in an older (>= 65 yrs) population that is cognitively intact at baseline. METHODS: We conducted a longitudinal population-based study of cognitively intact older adults. The participants were 65 years old or older and had Mini-Mental State Examination (MMSE) sum scores of 24 points or higher. The study included a 7.6-year follow-up. The use of benzodiazepines and related drugs (BZDs), antipsychotics (APs), antidepressants (ADs), opioids (Ops), anticholinergics (AChs) and antiepileptics (AEs) was determined at baseline and after a 7.6-years of the follow-up period. Cognitive functioning was used as an outcome variable measured with MMSE at baseline and at the mean follow-up of 7.6 years. Control variables were adjusted with analyses of covariance. RESULTS: After adjusting for control variables, the use of Ops and the concomitant use of Ops and BZDs as well as the use of Ops and any CNS medication were associated with cognitive decline. The use of AChs was associated with decline in cognitive functioning only in men. CONCLUSIONS: Of all the CNS medications analyzed in this study, the use of Ops may have the greatest effect on cognitive functioning in the ageing population. Due to small sample sizes these findings cannot be generalized to the unselected ageing population. More studies are needed concerning the long-term use of CNS medications, especially their concomitant use, and their potential cognitive effects. PMID- 22044596 TI - Bioengineering of coagulation factor VIII for efficient expression through elimination of a dispensable disulfide loop. AB - BACKGROUND: Heterologous expression of factor VIII (FVIII) is about two to three orders of magnitude lower than similarly sized proteins. Bioengineering strategies aimed at different structural and biochemical attributes of FVIII have been successful in enhancing its expression levels. OBJECTIVE: Disulfide bonds are vital to the proper folding, secretion and stability of most secretory proteins. In an effort to explore additional targeted bioengineering approaches, the role of disulfide bonds in FVIII secretion and function was probed in this study. METHODS AND RESULTS: Single and paired cysteine mutants were generated by substituting with serine or glycine residues and analyzed by transient transfection into COS-1 and CHO cells. Seven of the eight disulfide bonds in FVIII were found to be indispensable for proper secretion and function. However, elimination of the disulfide bond formed by C1899 and C1903 within the conserved A3 domain improved the secretion of FVIII. The addition of the C1899G/C1903G mutations to a previously described FVIII variant, 226/N6, with high secretion efficiency increased its secretion by 2.2-fold. Finally, the addition of the A1 domain mutation, F309S, in conjunction with the disulfide mutation had an additive effect, resulting in a net improvement in secretion of between 35 and 45 fold higher than wild-type FVIII in CHO cells. CONCLUSION: Such combined targeted bioengineering strategies may facilitate more efficient production of recombinant FVIII and contribute toward low-cost factor replacement therapy for hemophilia A. PMID- 22044597 TI - H. pylori exploits and manipulates innate and adaptive immune cell signaling pathways to establish persistent infection. AB - Persistent infection with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes carriers to a high gastric cancer risk, but has also been linked to protection from allergic, chronic inflammatory and autoimmune diseases. In the course of tens of thousands of years of co-existence with its human host, H. pylori has evolved elaborate adaptations that allow it to persist in the hostile environment of the stomach in the face of a vigorous innate and adaptive immune response. For this review, we have identified several key immune cell types and signaling pathways that appear to be preferentially targeted by the bacteria to establish and maintain persistent infection. We explore the mechanisms that allow the bacteria to avoid detection by innate immune cells via their pattern recognition receptors, to escape T-cell mediated adaptive immunity, and to reprogram the immune system towards tolerance rather than immunity. The implications of the immunomodulatory properties of the bacteria for the prevention of allergic and auto-immune diseases in chronically infected individuals are also discussed. PMID- 22044598 TI - The Foxconn suicides and their media prominence: is the Werther Effect applicable in China? AB - BACKGROUND: Media reporting of suicide and its relationship with actual suicide has rarely been investigated in Mainland China. The "Foxconn suicides" is a description referring to a string of suicides/attempts during 2010, all of which were related to a giant electrical manufacturing company, Foxconn. This study aimed to examine the clustering and copycat effects of the Foxconn suicides, and to investigate temporal patterns in how they were reported by the media in Mainland China, Hong Kong (HK), and Taiwan (TW). METHODS: Relevant articles were collected from representative newspapers published in three big cities in Mainland China (Beijing (BJ), Shenzhen (SZ), and Guangzhou (GZ)), HK, and TW, together with searching intensity data on the topic conducted using the Baidu search engine in Mainland China. The temporal clustering effects of the Foxconn suicides and their media prominence were assessed using the Kolmogorov-Smirnov test. The media reports of the Foxconn suicides' temporal patterns were explored using a nonparametric curve estimation method (that is, the local linear method). The potential mutual interactions between the Foxconn suicides and their media prominence were also examined, using logistic and Poisson regression methods. RESULTS: The results support a temporal clustering effect for the Foxconn suicides. The BJ-based newspapers' reporting and the occurrence of a Foxconn suicide/attempt are each found to be associated with an elevated chance of a further Foxconn suicide 3 days later. The occurrence of a Foxconn suicide also immediately influenced the intensity of both Baidu searching and newspaper reporting. Regional diversity in suicide reporting tempo-patterns within Mainland China, and similarities between HK and TW, are also demonstrated. CONCLUSIONS: The Foxconn suicides were temporally clustered. Their occurrences were influenced by the reporting of BJ-based newspapers, and contagion within the company itself. Further suicide research and prevention work in China should consider its special media environment. PMID- 22044599 TI - Visceral and mucosal involvement in neonatal haemangiomatosis. AB - BACKGROUND: Two types of neonatal haemangiomatosis (NH) are distinguished: diffuse which is associated with a high rate of mortality linked to mucosal/visceral involvement, and benign. OBJECTIVES: First, this study aimed to examine the frequency of mucosal and visceral (especially hepatic) involvement in NH, according to skin extension, and second, it aimed to examine clinical, pathological (with glucose transporter 1 (GLUT-1) immunostaining), and imaging features of NH, including follow-up data. METHODS: This was a descriptive retrospective study carried out in the University Hospital Center of Tours, France. RESULTS: The study included 19 patients with cutaneous NH (number of skin haemangiomas ranging from 5 to >100). Mucosal involvement was observed in 32% of all cases (100% and 19% in diffuse and other cutaneous cases respectively) and hepatic involvement in 42% (67% and 38% respectively). The number of hepatic haemangiomas ranged from 1 to >10. Half of the hepatic haemangiomas cases exhibited increased hepatic arterial blood flow. CONCLUSIONS: Mucosal and hepatic involvement was frequent in cases with a high number of cutaneous haemangiomas (>100), but only frequency of mucosal involvement was statistically significant (P = 0.021). PMID- 22044600 TI - MALDI-TOF MS Andromas strategy for the routine identification of bacteria, mycobacteria, yeasts, Aspergillus spp. and positive blood cultures. AB - All organisms usually isolated in our laboratory are now routinely identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using the Andromas software. The aim of this study was to describe the use of this strategy in a routine clinical microbiology laboratory. The microorganisms identified included bacteria, mycobacteria, yeasts and Aspergillus spp. isolated on solid media or extracted directly from blood cultures. MALDI-TOF MS was performed on 2665 bacteria isolated on solid media, corresponding to all bacteria isolated during this period except Escherichia coli grown on chromogenic media. All acquisitions were performed without extraction. After a single acquisition, 93.1% of bacteria grown on solid media were correctly identified. When the first acquisition was not contributory, a second acquisition was performed either the same day or the next day. After two acquisitions, the rate of bacteria identified increased to 99.2%. The failures reported on 21 strains were due to an unknown profile attributed to new species (9) or an insufficient quality of the spectrum (12). MALDI-TOF MS has been applied to 162 positive blood cultures. The identification rate was 91.4%. All mycobacteria isolated during this period (22) were correctly identified by MALDI-TOF MS without any extraction. For 96.3% and 92.2% of yeasts and Aspergillus spp., respectively, the identification was obtained with a single acquisition. After a second acquisition, the overall identification rate was 98.8% for yeasts (160/162) and 98.4% (63/64) for Aspergillus spp. In conclusion, the MALDI-TOF MS strategy used in this work allows a rapid and efficient identification of all microorganisms isolated routinely. PMID- 22044601 TI - Fatty acid profiling and molecular characterization of some freshwater microalgae from India with potential for biodiesel production. AB - We determined the fatty acid compositions of six species of freshwater microalgae belonging to the Chlorophyta, which were isolated from freshwater bodies in Assam, India. All six microalgae -Desmodesmus sp. DRLMA7, Desmodesmus elegans DRLMA13, Scenedesmus sp. DRLMA5, Scenedesmus sp. DRLMA9 Chlorella sp. DRLMA3 and Chlorococcum macrostigmatum DRLMA12-showed similar fatty acid profiles 16:0, 16:4, 18:1, 18:2, and 18:3 as major components. We also compared fatty acid compositions during the late exponential and stationary growth phases of D. elegans DRLMA13 and Scenedesmus sp. DRLMA9 in BG11 medium. We observed enhanced percentages of total saturated and monounsaturated fatty acids with a concomitant decrease in polyunsaturated fatty acid content upon the prolonged cultivation of both microalgae. Distinct morphological features of microalgal isolates were determined by scanning electron microscopic (SEM) studies. An ornamented cell wall was found in D. elegans DRLMA13, which is characteristic of small spineless species of Desmodesmus. The isolated microalgae were further distinguished through analysis of internal transcribed spacer 2 (ITS2) secondary structures and compensatory base changes (CBCs). Analysis of CBCs showed the relatedness of Chlorella sp. DRLMA3 with other Chlorella-like organisms, but it does not belong to the clade comprising Chlorella sensu stricto, which includes Chlorella vulgaris. The CBC count between Scenedesmus sp. DRLMA9 and other species of Scenedesmus provides evidence that this isolate represents a new species. PMID- 22044602 TI - Generalized shrinkage F-like statistics for testing an interaction term in gene expression analysis in the presence of heteroscedasticity. AB - BACKGROUND: Many analyses of gene expression data involve hypothesis tests of an interaction term between two fixed effects, typically tested using a residual variance. In expression studies, the issue of variance heteroscedasticity has received much attention, and previous work has focused on either between-gene or within-gene heteroscedasticity. However, in a single experiment, heteroscedasticity may exist both within and between genes. Here we develop flexible shrinkage error estimators considering both between-gene and within-gene heteroscedasticity and use them to construct F-like test statistics for testing interactions, with cutoff values obtained by permutation. These permutation tests are complicated, and several permutation tests are investigated here. RESULTS: Our proposed test statistics are compared with other existing shrinkage-type test statistics through extensive simulation studies and a real data example. The results show that the choice of permutation procedures has dramatically more influence on detection power than the choice of F or F-like test statistics. When both types of gene heteroscedasticity exist, our proposed test statistics can control preselected type-I errors and are more powerful. Raw data permutation is not valid in this setting. Whether unrestricted or restricted residual permutation should be used depends on the specific type of test statistic. CONCLUSIONS: The F-like test statistic that uses the proposed flexible shrinkage error estimator considering both types of gene heteroscedasticity and unrestricted residual permutation can provide a statistically valid and powerful test. Therefore, we recommended that it should always applied in the analysis of real gene expression data analysis to test an interaction term. PMID- 22044603 TI - Effect of chloroethene concentrations and granular activated carbon on reductive dechlorination rates and growth of Dehalococcoides spp. AB - This study focused on the investigation of (i) the tetrachloroethene (PCE) toxicity threshold of a reductively dechlorinating mixed culture containing Dehalococcoides spp., (ii) the adsorption of PCE on different types of granular activated carbon (GAC), and (iii) the bioavailability and reductive dechlorination in the presence of GAC. The abundance of Dehalococcoides spp. detected by quantitative real-time polymerase chain reaction (qPCR) was found to increase by 2-4 orders of magnitude during degradation of PCE. No degradation occurred at dissolved concentrations beyond 420 MUM (70 mg/L). Different adsorption isotherms were determined for thermally and chemically activated carbons. The addition of GAC to biological assays reduced the dissolved PCE concentration below the toxicity threshold. The combination of microbial reductive dechlorination with GAC adsorption proved to be a promising method for remediation of groundwater contaminated by high concentrations of chloroethenes. PMID- 22044604 TI - Watching the fetal brain at 'rest'. AB - Functional magnetic resonance imaging (fMRI) has allowed insights into the spatiotemporal distribution of human brain networks. According to the neurophysiological property of the fetal brain to generate spontaneous activity, we aimed to determine the feasibility of investigating the maturation of intrinsic networks, beginning at gestational week 20 in healthy human fetuses by combining resting-state fMRI and an analytical approach, independent component analysis (ICA). In this study, functional images of 16 fetuses with morphologically normal brain development, from 20 to 36 gestational weeks of age, were acquired on a 1.5T unit (Philips Medical Systems, Best, The Netherlands) using single-shot, gradient-recalled echo-planar imaging. After preprocessing (motion correction, brain extraction), images were analyzed using single-subject ICA. We visualized a bilateral occipital network and medial and lateral prefrontal activity pattern that involved the future Brodmann areas 9-11. Furthermore, there was one either predominantly right (3/7 cases) or left (4/7 cases) hemispheric lateralized network that involved the superior temporal cortical regions (Brodmann areas 22 and 39). Frequency oscillations were in the range of 0.01-0.06Hz for all networks. This study shows that resting-state networks (RSNs) are shaped and are detectable in utero. Further investigations of resting-state measurements in the fetus may therefore allow developmental brain activity monitoring and may provide insights into early brain function. PMID- 22044605 TI - Clinical/pathologic features and patient outcome in early onset endometrial carcinoma: a population based analysis and an institutional perspective from the Detroit metropolitan area, Michigan. AB - OBJECTIVE: Analyze tumor characteristics and outcomes in patients with endometrial carcinoma (EC)<40 years of age and compare them to the characteristics of patients >= 40 years of age. METHODS: 10,700 patients (305 patients <40 years of age) diagnosed between 1988 and 2007 with EC from the Metropolitan Detroit Cancer Surveillance System (MDCSS), and 884 patients (42 patients <40 years of age) diagnosed between 1996 and 2008 with EC from our institutional database were identified. Differences in clinical and demographic variables by age (<40 vs. >= 40) were assessed for statistical significance by chi-square tests. Cox proportional hazards models were used to calculate adjusted hazard ratios (HR) and their 95% confidence intervals (95% CI) to assess the risk of death from all causes. RESULTS: MDCSS based analysis: Patients<40 were more likely to present with low grade tumors (p<0.0001) and endometroid histology (p=0.0004) but less likely to undergo surgery (p=0.0007) or radiotherapy (p=0.0007). A multivariate analysis confirmed the significance of age, grade, and stage in all patients, and that of histologic type, surgery, and race in patients >= 40 as independent prognostic factors for overall survival. Institution based analysis: Patients<40 had a higher proportion of patients with BM I >= 30 (p=0.04), and presented with a higher frequency of well differentiated (p=0.04) endometrioid tumors (p=0.004) that are less prone to have deep myometrial invasion (p=0.008). CONCLUSION: This study supports the hypothesis of a disease that is biologically and genetically heterogeneous among women of different ages and ethnicities. PMID- 22044606 TI - A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer. AB - OBJECTIVE: Carboplatin-based combinations are commonly used in platinum-sensitive ovarian cancer (PSOC). Pemetrexed in combination with carboplatin has been shown to be feasible in a phase I study in PSOC. The primary objective of this subsequent phase II study was to determine the overall response rate (ORR; defined by Response Evaluation Criteria in Solid Tumors) of this combination in patients with recurrent PSOC. Secondary objectives included progression-free survival (PFS), overall survival (OS), and toxicity. METHODS: Patients with PSOC (defined by recurrence >= 6 months after completion of up to two lines of prior platinum-based therapy), measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. Pemetrexed 500 mg/m(2) was administered as a 10-minute infusion followed by carboplatin AUC 6 as a 30-minute infusion on day 1 of a 21-day cycle. RESULTS: Sixty-six patients were treated. Of the 61 patients evaluable for response, there were 20 responders (one complete response and 19 partial responses), for an ORR of 32.8% (95% CI: 21.3%, 46.0%). For the intent-to-treat population (all 66 patients), the median PFS was 9.4 months (95% CI: 8.3, 11.1), with 22.7% censoring. Median OS was not reached due to the high censoring rate. There was one drug-related death (multi-organ failure). The most common drug-related grade 3/4 toxicities were neutropenia (39.4%), thrombocytopenia (24.2%), carboplatin hypersensitivity (9.1%), nausea (6.1%), and vomiting (6.1%). CONCLUSIONS: Carboplatin AUC 6 and pemetrexed 500 mg/m(2) has a low incidence of serious toxicities. Defining the platinum-based combination with the best therapeutic index would require a prospective phase III study. PMID- 22044607 TI - Xeroderma pigmentosum. AB - Xeroderma pigmentosum (XP) is defined by extreme sensitivity to sunlight, resulting in sunburn, pigment changes in the skin and a greatly elevated incidence of skin cancers. It is a rare autosomal recessive disorder and has been found in all continents and racial groups. Estimated incidences vary from 1 in 20, 000 in Japan to 1 in 250, 000 in the USA, and approximately 2.3 per million live births in Western Europe.The first features are either extreme sensitivity to sunlight, triggering severe sunburn, or, in patients who do not show this sun sensitivity, abnormal lentiginosis (freckle-like pigmentation due to increased numbers of melanocytes) on sun-exposed areas. This is followed by areas of increased or decreased pigmentation, skin aging and multiple skin cancers, if the individuals are not protected from sunlight. A minority of patients show progressive neurological abnormalities. There are eight XP complementation groups, corresponding to eight genes, which, if defective, can result in XP. The products of these genes are involved in the repair of ultraviolet (UV)-induced damage in DNA. Seven of the gene products (XPA through G) are required to remove UV damage from the DNA. The eighth (XPV or DNA polymerase eta) is required to replicate DNA containing unrepaired damage. There is wide variability in clinical features both between and within XP groups. Diagnosis is made clinically by the presence, from birth, of an acute and prolonged sunburn response at all exposed sites, unusually early lentiginosis in sun-exposed areas or onset of skin cancers at a young age. The clinical diagnosis is confirmed by cellular tests for defective DNA repair. These features distinguish XP from other photodermatoses such as solar urticaria and polymorphic light eruption, Cockayne Syndrome (no pigmentation changes, different repair defect) and other lentiginoses such as Peutz-Jeghers syndrome, Leopard syndrome and Carney complex (pigmentation not sun associated), which are inherited in an autosomal dominant fashion. Antenatal diagnosis can be performed by measuring DNA repair or by mutation analysis in CVS cells or in amniocytes. Although there is no cure for XP, the skin effects can be minimised by rigorous protection from sunlight and early removal of pre-cancerous lesions. In the absence of neurological problems and with lifetime protection against sunlight, the prognosis is good. In patients with neurological problems, these are progressive, leading to disabilities and a shortened lifespan. PMID- 22044608 TI - Mirror images: fish versus terrestrial animals. PMID- 22044610 TI - D-dimer levels as a prognostic factor for determining oncological outcomes in musculoskeletal sarcoma. AB - BACKGROUND: Plasma d-dimer levels have been associated with the status of tumor progression or oncological outcomes in cancer. Although there are many evidences suggesting the involvement of procoagulant trend in musculoskeletal sarcoma, no clinical data on d-dimer levels and oncological outcome of musculoskeletal sarcoma has been reported. METHODS: In this study, we included a total of 85 patients who were diagnosed with musculoskeletal sarcoma and treated at our institute. Plasma d-dimer levels were determined before performing any clinical intervention, including open biopsy, chemotherapy, radiotherapy or tumor resection. We evaluated the effect of d-dimer levels and other clinicopathological factors on oncological outcomes of patients. RESULTS: Upregulation of plasma d-dimer levels proved to be an independent risk factor for metastasis and lethal outcome of patients with musculoskeletal sarcoma. CONCLUSIONS: Upregulation of plasma d-dimer levels were indicated poor oncological outcome in metastasis and total survival rate of musculoskeletal sarcoma patients. Hence d-dimer levels may be a helpful marker for evaluating the tumor progression status and prognosis of musculoskeletal sarcoma. PMID- 22044609 TI - Motivational brief intervention for the prevention of sexually transmitted infections in travelers: a randomized controlled trial. AB - BACKGROUND: Sexually transmitted infections (STIs) are among the frequent risks encountered by travelers. Efficient interventions are needed to improve the understanding of the risks of STIs. We investigated the potential benefits of a motivational brief intervention (BI) and the provision of condoms on the engagement in unprotected casual sex. METHODS: 3-arm randomized controlled trial performed among single travelers aged 18-44 years visiting a travel clinic in Switzerland. The main outcomes were the prevalence of casual unprotected sexual intercourse and their predictors. RESULTS: 5148 eligible travelers were seen from 2006 to 2008. 1681 agreed to participate and 1115 subjects (66%) completed the study. 184/1115 (17%) had a casual sexual relationship abroad and overall 46/1115 (4.1%) had inconsistently protected sexual relations. Women (adjusted OR 2.7 [95%CI 1.4-5.6]) and travelers with a history of past STI (adjusted OR 2.8 [95%CI 1.1-7.4]) had more frequent casual sexual relationships without consistent protection. Regarding the effect of our intervention, the prevalence of subjects using condoms inconsistently was 28% (95%CI16-40) in the motivational BI group, 24% (95%CI10-37) in the condoms group and 24% (95%CI14-33) in the control group (p = 0.7). CONCLUSION: This study showed that a motivational brief intervention and/or the provision of free condoms did not modify risky sexual behavior of young travelers. The rate of inconsistently protected sexual relationships during travel was however lower than expected TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01056536. PMID- 22044611 TI - Practical aspects of a visual aid to decision making. AB - BACKGROUND: Previous research has demonstrated that people with mild intellectual disabilities (ID) have difficulty in 'weighing up' information, defined as integrating disparate items of information in order to reach a decision. However, this problem could be overcome by the use of a visual aid to decision making. In an earlier study, participants were taught to translate information about the pros and cons of different choices into a single evaluative dimension, by manipulating green (good) and red (bad) bars of varying lengths (corresponding to the value ascribed). Use of the visual calculator increased the consistency of performance (and decreased impulsive responding) in a temporal discounting task, and increased the amount of information that participants provided to justify their decisions in scenario-based financial decision-making tasks. METHODS: The present study examined some practical aspects of visual calculator training, using a pen-and-paper version of two temporal discounting tasks. Participants with mild ID were tested, individually and in a group setting, before and after training in the group setting, and 2 months later. RESULTS: (i) The visual aid improved temporal discounting performance using pen-and-paper presentation in a group setting as effectively as previously demonstrated using computer-based individual presentation. (ii) Following withdrawal of the aid, improvements in temporal discounting performance were maintained at 1 day post training, but lost following a 2-month hiatus; however, participants showed perfect retention, over 2 months, of how to use the aid. (iii) In addition to decreasing impulsivity in a hypothetical task, as previously demonstrated, use of the visual calculator also increased the ability of impulsive participants to wait in real time. CONCLUSION: The results suggest that the visual calculator has practical applicability to support decision making by people with mild ID in community settings. PMID- 22044612 TI - Proteinase-activated receptor-4 evoked colorectal analgesia in mice: an endogenously activated feed-back loop in visceral inflammatory pain. AB - BACKGROUND: Activation of proteinase-activated receptor-4 (PAR-4) from the colonic lumen has an antinociceptive effect to colorectal distension (CRD) in mice in basal conditions. We aimed to determine the functional localization of the responsible receptors and to test their role in two different hyperalgesia models. METHODS: Mice received PAR-4 activating peptide (PAR-4-AP, AYPGKF-NH(2)) or vehicle intraperitoneally (IP), and abdominal EMG response to CRD was measured. The next group received PAR-4-AP intracolonically (IC) with or without 2,4,6-triaminopyrimidine, a chemical tight junction blocker, before CRD. The SCID mice were used to test the role of lymphocytes in the antihyperalgesic effect. The effects of PAR-4-AP and PAR-4-antagonist (P4pal-10) were evaluated in water avoidance stress (WAS) model and low grade 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis. Spinal Fos protein expression was visualized by immunohistochemistry. KEY RESULTS: The antinociceptive effect of PAR-4-AP disappeared when was administrered IP, or with the blockade of colonic epithelial tight junctions, suggesting that PAR-4-AP needs to reach directly the nerve terminals in the colon. The CRD-induced spinal Fos overexpression was reduced by 43% by PAR-4-AP. The PAR-4-AP was antihyperalgesic in both hyperalgesia models and in mice with impaired lymphocytes. The PAR-4-antagonist significantly increased the TNBS, but not the WAS-induced colonic hyperalgesia. CONCLUSIONS & INFERENCES: The antinociceptive effect of PAR-4-AP depends on its penetration to the colonic mucosa. The PAR-4 activation is endogenously involved as a feedback loop to attenuate inflammatory colonic hyperalgesia to CRD. PMID- 22044613 TI - Assessment of left ventricular mechanical dyssynchrony using real time three dimensional echocardiography: a comparative study to Doppler tissue imaging. AB - PURPOSE: To assess left ventricular mechanical dyssynchrony (LVMD) using real time three-dimensional echocardiography (RT3DE) and comparing it with the different dyssynchrony indices derived from Doppler tissue imaging (DTI) for the same patient. METHODS: The study included 60 consecutive patients who were considered candidates for CRT, i.e., having ejection fraction <=35%, NYHA class III or ambulatory class IV, QRS duration >=120 msec, on optimal pharmacological therapy. Apical RT3DE full volumes were obtained and analyzed to generate the systolic dyssynchrony index (SDI-16), which is the standard deviation of the time to minimal systolic volume of the 16 segments of LV. Color-coded DTI was performed for the three standard apical views with estimation of the mechanical dyssynchrony index (12 Ts-SD), which is the standard deviation of the time to peak systolic velocity at 12 segments of LV. RESULTS: SDI-16 was 10.96 +/- 3.9% (cutoff value: 8.3%), while Ts-SD was 38 +/- 10.2 msec (cutoff value: 32.6 msec). The concordance rate for both indices was 75%; however, there was no correlation between both indices (r = 0.14, P = 0.3). SDI-16 showed good correlation with QRS duration (r = 0.45, P < 0.001) and inverse correlation with left ventricular ejection fraction (LVEF) calculated by RT3DE (r =-0.37, P = 0.004), while 12 Ts SD index showed no correlation with QRS duration (r =-0.0082, P = 0.51) or 2D LVEF (r =-0.26, P = 0.84). CONCLUSIONS: RT3DE can quantify LVMD by providing the SDI-16 and it may prove to be more useful than DTI as it shows increasing dyssynchrony with increased QRS duration and decreased LVEF. PMID- 22044614 TI - Discussing trainee participation in cataract surgery: what are patients told? PMID- 22044615 TI - Survival after treatment for carcinoma invading bladder muscle: a Dutch population-based study on the impact of hospital volume. AB - Study Type - Prognosis (cohort). Level of Evidence 2a. What's known on the subject? and What does the study add? The subject of mortality and survival rates after radical cystectomies in high-volume hospitals in comparison to low-volume hospitals has been extensively studied. Postoperative mortality is known to be significantly lower with high-volume providers, but for survival rates there was only a trend forwards this finding. For this reason, we performed this Dutch population-based study on survival rates, to see if we had enough power to support this trend with significant findings. To our knowledge, this is the first study of good quality showing a significant beneficial effect for survival in high-volume hospitals. OBJECTIVE: * To examine the volume-outcome relationship for carcinoma invading bladder muscle (MIBC) with respect to differences in survival rates among all hospitals in the Netherlands as a guide for regionalization initiatives. MATERIALS AND METHODS: * This population-based retrospective study included all patients (n= 13 033) newly diagnosed with MIBC during the period 1999-2008 in the Netherlands, selected from the Netherlands Cancer Registry. * Data were collected on demographics, morphology, stage at diagnosis and after surgery, primary treatment, vital status and date of follow up or death. * The relative survival rate (RSR) per treatment was analysed for age, stage and hospital surgical volume. RESULTS: * Overall 5 and 10-year RSR for all treatments of MIBC was 32% and 25%, respectively. * Although 71.7% of the patients featured stages II and III, radical cystectomy was only performed in only 42% and 44% of these patients, respectively. * Relative survival for MIBC remained unchanged in the two consecutive time periods (1999-2003 and 2004-2008). * In all, 34% of patients diagnosed in low-volume hospitals (<10 cystectomies/year) underwent cystectomy vs 42% of those diagnosed in high-volume hospitals (P= 0.000). * In a multivariate analysis long-term survival (>30 days after surgery) was significantly lower in patients after cystectomy for stage II/III in low-volume hospitals (hazard ratio [HR] 1.17, P= 0.036). A high lymph node count (>20) was associated with a lower risk of death (HR 0.52, P= 0.000). CONCLUSIONS: * The 10-year RSR for patients with MIBC in the Netherlands was modest (25%) and has remained unchanged in the last decade. * The chance of undergoing cystectomy is significantly higher in high-volume hospitals. Long-term survival after cystectomy is higher in high-volume hospitals. * Regionalization of bladder cancer treatments could improve overall outcomes. PMID- 22044616 TI - Park gazettement and integrated conservation and development as factors in community conflict at Bwindi Impenetrable Forest, Uganda. AB - Conflicts between protected-area managers and local people are common, but the drivers of conflict are rarely analyzed. This limits opportunities to identify strategies that reduce conflict and the magnitude of resulting threats to conservation. Integrated conservation and development (ICD) was adopted at Bwindi Impenetrable Forest, Uganda, to reduce conflict during gazettement of the national park, but the success of this approach remains contested. We retrieved documents of conflict written by park staff and local people from 1986 through 2000 (before, during, and after gazettement). We extracted data on 48 incidences of violent conflict and categorized them by gazettement period, area, instigator, and type to undertake a historical analysis of the triggers of violent conflict at Bwindi. Before and during gazettement, local villagers instigated most of the conflict incidents when law-enforcement efforts sought to halt commercial activities within Bwindi. No conflict arose from the arrest of villagers collecting subsistence resources during these periods. After gazettement, prohibitions on commercial activities continued to drive conflict even though villagers collecting subsistence resources were arrested more frequently than before gazettement, and local attitudes toward the park had improved following receipt of ICD benefits. Law-enforcement efforts targeted commercial activities to reduce this threat to Bwindi's mountain gorillas (Gorilla beringei beringei), although the activities remained important income sources for people in villages near Bwindi. Losing commercial income following gazettement therefore appeared to be their primary motivation for instigating conflict with park rangers. Prohibitions on subsistence resource use triggered conflict less often. Our use of typologies for a multivariate conflict analysis demonstrates that by identifying differences between effects of conservation as drivers of conflict, conflict analysis can enable a more strategic deployment of conflict-resolution measures that could further conservation efforts. At Bwindi targeting ICD toward individuals who lost benefits from commercial activities may strengthen the role of ICD in conflict resolution and conservation. PMID- 22044617 TI - Genetic modulation of the FV(Leiden)/normal FV ratio and risk of venous thrombosis in factor V Leiden heterozygotes. AB - BACKGROUND AND OBJECTIVES: The factor (F)V Leiden mutation causes activated protein C (APC) resistance by decreasing the susceptibility of FVa to APC mediated inactivation and by impairing the APC-cofactor activity of FV in FVIIIa inactivation. However, APC resistance and the risk of venous thromboembolism (VTE) vary widely among FV Leiden heterozygotes. Common F5 genetic variation probably contributes to this variability. PATIENTS/METHODS: APC resistance was determined in 250 FV Leiden heterozygotes and 133 normal relatives using the prothrombinase-based assay, which specifically measures the susceptibility of plasma FVa to APC. The effects of 12 F5 single-nucleotide polymorphisms (SNPs) on the normalized APC sensitivity ratio (nAPCsr) and on FV levels were determined by multiple regression analysis. RESULTS: In FV Leiden heterozygotes,VTE risk increased with increasing nAPCsr, reaching an odds ratio (OR) of 9.9 (95% confidence interval [CI] 1.2-80.5) in the highest nAPCsr quartile. The minor alleles of several F5 SNPs, including 327 A/G (Q51Q), 409 G/C (D79H), 2663 A/G(K830R, T2 haplotype), 6533 T/C (M2120T) and 6755 A/G (D2194G, R2 haplotype), increased the nAPCsr in FV Leiden heterozygotes, but not in their normal relatives. Most of these effects could be attributed to a shift in the FV(Leiden)/normal FV ratio. Four FV Leiden heterozygotes with extremely high nAPCsr turned out to be pseudo-homozygotes, i.e. they carried a deleterious mutation on the non-Leiden allele. CONCLUSIONS: In FV Leiden heterozygotes, the prothrombinase-based nAPCsr is a marker of VTE risk and is modulated by common F5 SNPs that affect the FV(Leiden)/normal FV ratio in plasma. PMID- 22044618 TI - Complete genomic sequence of a reovirus isolated from grass carp in China. AB - A reovirus was isolated from sick grass carp in Guangdong, China in 2009, and tentatively named 'grass carp reovirus Guangdong 108 strain' (GCRV-GD108). This reovirus was propagated in grass carp snout fibroblast cell line PSF with no obvious cytopathic effects. Its genome was 24,703bp in length with a 50% G+C content and 11 dsRNA segments encoding 11 proteins instead of 12 proteins. It has been classified as an Aquareovirus (AQRV). Sequence comparisons showed that it possessed only 7 homologous proteins to grass carp reovirus (GCRV) (with 17.6 45.8% identities), but 9 homologous proteins to mammalian orthoreoviruses (MRV) (with 15-46% identities). GCRV-GD108 lacked homology to VP7, NS4&NS5 and NS3 of GCRV, while it had sigma1 and sigma NS homology to MRV. VP2 of GCRV-GD108 shared high amino acid sequence identity (44-47%) with AQRVs, whereas VP5 did not exhibit much identity (24-25%) to AQRVs. Conserved terminal sequences, 5'-GUAAUUU and UUCAUC-3', were found in all of the 11 genomic segments of GCRV-GD108 at the 5' and 3' non-coding regions (NCRs) of the segments. The 5' NCRs of GCRV-GD108 was similar to GCRV, but differed from other species of AQRV or Orthoreoviruses (ORV). Phylogenetic analysis of coat proteins belonging to Reoviridae, VP1-VP6, showed that GCRV-GD108 clustered with AQRVs and grouped with ORVs, suggesting that GCRV-GD108 belonged to the genus Aquareovirus but was distinctive from any known species of AQRV. Morphological and pathological analyses, and genetic characterization of GCRV-GD108 suggested that it may be a new species of AQRV and it was more closely related with ORVs than other AQRVs. In addition, RT-PCR analysis of diseased grass carp samples collected from different regions of China indicated that these viruses displayed high similarities to each other (95.3 99.4%). They also shared high sequence similarities to GCRV-GD108 (96.7-99.4%), indicating that GCRV-GD108 is representative of the prevalence strain in southern China. PMID- 22044619 TI - Infection of Hantaan virus strain AA57 leading to pulmonary disease in laboratory mice. AB - Hantaan virus (HTNV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). The pathogenesis of HFRS has not been fully elucidated, mainly due to the lack of a suitable animal model. In laboratory mice, HTNV causes encephalitis. However, that symptom is dissimilar to human hantavirus infections. We found that HTNV strain AA57 (isolated from Apodemus agrarius in Far East Russia) caused pulmonary disease in 2-week-old ICR mice. The clinical signs of the infected mice were piloerection, trembling, hunching, labored breathing, and body-weight loss. A large volume of pleural effusion was collected from thoracic cavities of the dead mice. Overall, 45% of the mice inoculated with 3000 focus forming units (FFU) of the virus began to show clinical symptoms at 8 days post inoculation, and 25% of the inoculated mice died within 3 days of onset of the disease. The morbidity and mortality rates of the mice inoculated with 30 30,000FFU of HTNV strain AA57 were roughly equivalent. The highest rates of virus positivity (11/12) and the highest titers of HTNV strain AA57 were detected in the lungs of the dead mice, while lower detection rates and viral titers were found in the heart, kidneys, spleen, and brain. Interstitial pneumonia, perivascular edema, hemorrhage, inflammatory infiltration and vascular failure were observed in the lungs of the sick mice. Hantaviral antigens were detected in the lung endothelial cells of the sick mice. The symptoms and pathology of this mouse model resemble those of hantavirus pulmonary syndrome (HPS) and, to a certain extent, those of HFRS. This is the first report that, in laboratory mice, the HFRS-related hantavirus causes a HPS-like disease and shares some symptom similarities with HFRS. PMID- 22044620 TI - Orally active zwitterionic factor Xa inhibitors with long duration of action. AB - We have optimized 2-aminomethylphenylamine derivative as a factor Xa inhibitor. Several polar functional groups were introduced in the central phenyl ring, and we focused on zwitter ionic compound showing continuous inhibitory activity in oral administration test. In vitro and oral activities were improved by optimization of S1 and S4 ligands. Incorporating the interaction with S1-beta pocket enhanced in vitro factor Xa inhibitory activity to less than 1 nM. Many zwitter ionic compounds showed long duration of action and potent inhibitory activity and high AUC values in oral administration tests to monkeys. PMID- 22044621 TI - ortho-Quinone tanshinones directly inhibit telomerase through an oxidative mechanism mediated by hydrogen peroxide. AB - The tanshinone natural products possess a variety of pharmacological properties including anti-bacterial, anti-inflammatory, anti-oxidant, and anti-neoplastic activity. The molecular basis of these effects, however, remains largely unknown. In the present study, we explored the direct effect of tanshinones on the enzyme telomerase. Telomerase is up-regulated in the majority of cancer cells and is essential for their survival, making it a potential anti-cancer drug target. We found that the ortho-quinone tanshinone II-A inhibits telomerase in a time- and DTT-dependent fashion, and the hydrogen peroxide scavenger catalase protected telomerase from inactivation. These findings demonstrate that ortho-quinone containing tanshinones can inhibit telomerase owing to their ability to generate reactive oxygen species. The results also provide evidence that telomerase is directly and negatively regulated by reactive oxygen species. PMID- 22044624 TI - Mitochondrial-nuclear co-evolution and its effects on OXPHOS activity and regulation. AB - Factors required for mitochondrial function are encoded both by the nuclear and mitochondrial genomes. The order of magnitude higher mutation rate of animal mitochondrial DNA (mtDNA) enforces tight co-evolution of mtDNA and nuclear DNA encoded factors. In this essay we argue that such co evolution exists at the population and inter-specific levels and affect disease susceptibility. We also argue for the existence of three modes of co-evolution in the mitochondrial genetic system, which include the interaction of mtDNA and nuclear DNA encoded proteins, nuclear protein - mtDNA-encoded RNA interaction within the mitochondrial translation machinery and nuclear DNA encoded proteins-mtDNA binging sites interaction in the frame of the mtDNA replication and transcription machineries. These modes of co evolution require co-regulation of the interacting factors encoded by the two genomes. Thus co evolution plays an important role in modulating mitochondrial activity. This article is part of a Special Issue entitled: Mitochondrial Gene Expression. PMID- 22044625 TI - Immunotherapy of infections caused by rare filamentous fungi. AB - Invasive fungal infections caused by rare filamentous fungi constitute a significant cause of morbidity and mortality in patients with defective immune responses. Despite the advent of new antifungal agents, the problem is escalating as the number of susceptible hosts increases and virulent, more resistant fungal strains emerge. There is evidence that reconstitution of the host immune function is a major contributor to the resolution of these infections. Therapeutic modalities aimed at increasing phagocyte numbers, such as granulocyte transfusions, stimulating the immune response, such as administration of haematopoietic growth factors and other proinflammatory cytokines, or indirectly augmenting immune function have shown promising results in the preclinical setting. Because of the rarity of the infections, multicentre clinical trials are needed to demonstrate the efficacy and safety of the new immunomodulating approaches. PMID- 22044622 TI - The role of epigenetic variation in the pathogenesis of systemic lupus erythematosus. AB - The focus of the present review is on the extent to which epigenetic alterations influence the development of systemic lupus erythematosus. Lupus is a systemic autoimmune disease characterized by the production of autoantibodies directed at nuclear self-antigens. A DNA methylation defect in CD4+ T cells has long been observed in idiopathic and drug-induced lupus. Recent studies utilizing high throughput technologies have further characterized the nature of the DNA methylation defect in lupus CD4+ T cells. Emerging evidence in the literature is revealing an increasingly interconnected network of epigenetic dysregulation in lupus. Recent reports describe variable expression of a number of regulatory microRNAs in lupus CD4+ T cells, some of which govern the expression of DNA methyltransferase 1. While studies to date have revealed a significant role for epigenetic defects in the pathogenesis of lupus, the causal nature of epigenetic variation in lupus remains elusive. Future longitudinal epigenetic studies in lupus are therefore needed. PMID- 22044626 TI - Colour homogeneity and visual perception of age, health and attractiveness of male facial skin. AB - BACKGROUND: Visible facial skin condition in females is known to affect perception of age, health and attractiveness. Skin colour distribution in shape- and topography-standardized female faces, driven by localized melanin and haemoglobin, can account for up to twenty years of apparent age perception. Although this is corroborated by an ability to discern female age even in isolated, non-contextual skin images, a similar effect in the perception of male skin is yet to be demonstrated. OBJECTIVES: To investigate the effect of skin colour homogeneity and chromophore distribution on the visual perception of age, health and attractiveness of male facial skin. METHODS: Cropped images from the cheeks of facial images of 160 Caucasian British men aged 10-70 years were blind rated for age, health and attractiveness by a total of 308 participants. In addition, the homogeneity of skin images and corresponding eumelanin/oxyhaemoglobin concentration maps were analysed objectively using Haralick's image segmentation algorithm. RESULTS: Isolated skin images taken from the cheeks of younger males were judged as healthier and more attractive. Perception of age, health and attractiveness was strongly related to melanin and haemoglobin distribution, whereby more even distributions led to perception of younger age and greater health and attractiveness. The evenness of melanized features was a stronger cue for age perception, whereas haemoglobin distribution was associated more strongly with health and attractiveness perception. CONCLUSIONS: Male skin colour homogeneity, driven by melanin and haemoglobin distribution, influences perception of age, health and attractiveness. PMID- 22044627 TI - Liver fluke-induced hepatic oxysterols stimulate DNA damage and apoptosis in cultured human cholangiocytes. AB - Oxysterols are cholesterol oxidation products that are generated by enzymatic reactions through cytochrome P450 family enzymes or by non-enzymatic reactions involving reactive oxygen and nitrogen species. Oxysterols have been identified in bile in the setting of chronic inflammation, suggesting that biliary epithelial cells are chronically exposed to these compounds in certain clinical settings. We hypothesized that biliary oxysterols resulting from liver fluke infection participate in cholangiocarcinogenesis. Using gas chromatography/mass spectrometry, we identified oxysterols in livers from hamsters infected with Opisthorchis viverrini that develop cholangiocarcinoma. Five oxysterols were found: 7-keto-cholesta-3,5-diene (7KD), 3-keto-cholest-4-ene (3K4), 3-keto cholest-7-ene (3K7), 3-keto-cholesta-4,6-diene (3KD), and cholestan 3beta,5alpha,6beta-triol (Triol). Triol and 3K4 were found at significantly higher levels in the livers of hamsters with O. viverrini-induced cholangiocarcinoma. We therefore investigated the effects of Triol and 3K4 on induction of cholangiocarcinogenesis using an in vitro human cholangiocyte culture model. Triol- and 3K4-treated cells underwent apoptosis. Western blot analysis showed significantly increased levels of Bax and decreased levels of Bcl 2 in these cells. Increased cytochrome c release from mitochondria was found following treatment with Triol and 3K4. Triol and 3K4 also induced formation of the DNA adducts 1,N(6)-etheno-2'-deoxyadenosine, 3,N(4)-etheno-2'-deoxycytidine and 8-oxo-7,8-dihydro-2'-deoxyguanosine in cholangiocytes. The data suggest that Triol and 3K4 cause DNA damage via oxidative stress. Chronic liver fluke infection increases production of the oxysterols Triol and 3K4 in the setting of chronic inflammation in the biliary system. These oxysterols induce apoptosis and DNA damage in cholangiocytes. Insufficient and impaired DNA repair of such mutated cells may enhance clonal expansion and further drive the change in cellular phenotype from normal to malignant. PMID- 22044628 TI - Helicobacter pylori vacuolating toxin A and apoptosis. AB - VacA, the vacuolating cytotoxin A of Helicobacter pylori, induces apoptosis in epithelial cells of the gastic mucosa and in leukocytes. VacA is released by the bacteria as a protein of 88 kDa. At the outer surface of host cells, it binds to the sphingomyelin of lipid rafts. At least partially, binding to the cells is facilitated by different receptor proteins. VacA is internalized by a clathrin independent mechanism and initially accumulates in GPI-anchored proteins-enriched early endosomal compartments. Together with early endosomes, VacA is distributed inside the cells. Most of the VacA is eventually contained in the membranes of vacuoles. VacA assembles in hexameric oligomers forming an anion channel of low conductivity with a preference for chloride ions. In parallel, a significant fraction of VacA can be transferred from endosomes to mitochondria in a process involving direct endosome-mitochondria juxtaposition. Inside the mitochondria, VacA accumulates in the mitochondrial inner membrane, probably forming similar chloride channels as observed in the vacuoles. Import into mitochondria is mediated by the hydrophobic N-terminus of VacA. Apoptosis is triggered by loss of the mitochondrial membrane potential, recruitment of Bax and Bak, and release of cytochrome c. PMID- 22044629 TI - Identifying features of bipolarity in patients with first-episode postpartum depression: findings from the international BRIDGE study. AB - OBJECTIVES: The aims of this study were to assess rates of bipolar spectrum disorders in women experiencing their first episode of postpartum depression, and to find out features indicative of bipolarity in these patients. METHODS: As part of the international BRIDGE study designed to detect hypo/mania in patients with a major depressive episode, 52 (5.85%) were found to experience a first episode of postpartum (FEPP) depression, whereas 833 (94.13%) had a first episode of nonpostpartum (FENPP) depression. Hypo/mania was assessed using varying definitions of bipolarity, and the two groups compared on sociodemographic, family history and clinical characteristics. RESULTS: Compared to FENPP depressive patients, women with FEPP depression had higher rates of bipolar disorders, with more hypo/mania in first degree relatives. Psychotic symptoms, atypical features, mixed depression, younger age at onset, high number of prior episodes, episodes of short duration, switches on antidepressants, seasonality of mood episodes as well as mood episodes with free intervals were found to be more frequent in FEPP depressives. LIMITATIONS: The following are the limitations of this study: centres not randomly selected, recall bias, cross-sectional design, and limited training of participating psychiatrists. CONCLUSIONS: This study confirms, in women experiencing a first depressive episode, high rates (15 to 50%) of bipolar disorders during the postpartum period and is the first to systematically assess and demonstrate the higher prevalence of identifying features of bipolarity in FEPP versus FENPP depression. Early recognition of bipolarity in these patients may help prevent the harmful consequences of this illness. PMID- 22044630 TI - Negative affectivity moderated by BDNF and stress response. AB - BACKGROUND: Gene*environment (G*E) interactions are known to predict susceptibility to disorders such as depression and anxiety. Adverse experiences in childhood and number of stressful life events (SLEs) have been widely studied as environmental risk factors; however, SLE response has not yet been studied. Here we present a first attempt at the analysis of the interaction between the response to personal and academic stressful events during different life stages and the gene polymorphisms 5-HTTLPR, 5-HTTVNTR (STin2), HTR1A C(-1019)G, and BDNF Val66Met in the prediction of negative affectivity (NA). METHODS: Standardized questionnaires (ST-DEP and STAI) were used to measure negative affectivity derived from depression and anxiety in a sample of 303 undergraduate students. Response to stressful events during childhood, high school and college years was evaluated together with a self-report personal history form. Multiple logistic regression analysis was used to perform association and G*E analysis. RESULTS: Negative affectivity is strongly associated with childhood maltreatment and stress response. Gene associations were observed between 5-HTTVNTR allele 12 and the S_12 haplotype with NA derived from high scores in both depression and anxiety. The BDNF gene variant was not associated with NA derived from depression or anxiety alone, but it was associated with the comorbid presentation. A significant G*E interaction was observed between the BDNF Val66Met and stress response during childhood and college years although the risk for negative affectivity conferred by stress response during childhood was only significant among the Met allele carriers, while stress response during college years was a significant risk factor regardless of the BDNF Val66Met genotype. A significant G*E interaction was also found between the HTR1A C(-1019)G variant and childhood maltreatment. LIMITATIONS: The study has two main limitations, sample size is low and retrospective recognition of SLEs is a concern. CONCLUSION: Altogether, our results demonstrate that the BDNF Val66Met variant moderates the effect of stress during both childhood and college years; although this effect seems to be more critical during childhood given that the risk conferred by childhood stress was restricted to the Met allele carriers. We also found that the HTR1A C(-1019)G variant moderates the effect of childhood maltreatment in our study population. PMID- 22044631 TI - Distinguishing symptom dimensions of depression and anxiety: an integrative approach. AB - BACKGROUND: Clark and Watson developed the tripartite model in which a symptom dimension of 'negative affect' covers common psychological distress that is typically seen in anxious and depressed patients. The 'positive affect' and 'somatic arousal' dimensions cover more specific symptoms. Although the model has met much support, it does not cover all relevant anxiety symptoms and its negative affect dimension is rather unspecific. Therefore, we aimed to extend the tripartite model in order to describe more specific symptom patterns with unidimensional measurement scales. METHOD: 1333 outpatients provided self report data. To develop an extended factor model, exploratory factor analysis (EFA) was conducted in one part of the data (n=578). Confirmatory factor analysis (CFA) was conducted in the second part (n=755), to assess model-fit and comparison with other models. Rasch analyses were done to investigate the unidimensionality of the factors. RESULTS: EFA resulted in a 6-factor model: feelings of worthlessness, fatigue, somatic arousal, anxious apprehension, phobic fear and tension. CFA in the second sample showed that a 6-factor model with a hierarchical common severity factor fits the data better than alternative 1- and 3-factor models. Rasch analyses showed that each of the factors and the total of factors can be regarded as unidimensional measurement scales. LIMITATIONS: The model is based on a restricted symptom-pool: more dimensions are likely to exist. CONCLUSION: The extended tripartite model describes the clinical state of patients more specifically. This is relevant for both clinical practice and research. PMID- 22044632 TI - Spatial heterogeneity, frequency-dependent selection and polymorphism in host parasite interactions. AB - BACKGROUND: Genomic and pathology analysis has revealed enormous diversity in genes involved in disease, including those encoding host resistance and parasite effectors (also known in plant pathology as avirulence genes). It has been proposed that such variation may persist when an organism exists in a spatially structured metapopulation, following the geographic mosaic of coevolution. Here, we study gene-for-gene relationships governing the outcome of plant-parasite interactions in a spatially structured system and, in particular, investigate the population genetic processes which maintain balanced polymorphism in both species. RESULTS: Following previous theory on the effect of heterogeneous environments on maintenance of polymorphism, we analysed a model with two demes in which the demes have different environments and are coupled by gene flow. Environmental variation is manifested by different coefficients of natural selection, the costs to the host of resistance and to the parasite of virulence, the cost to the host of being diseased and the cost to an avirulent parasite of unsuccessfully attacking a resistant host. We show that migration generates negative direct frequency-dependent selection, a condition for maintenance of stable polymorphism in each deme. Balanced polymorphism occurs preferentially if there is heterogeneity for costs of resistance and virulence alleles among populations and to a lesser extent if there is variation in the cost to the host of being diseased. We show that the four fitness costs control the natural frequency of oscillation of host resistance and parasite avirulence alleles. If demes have different costs, their frequencies of oscillation differ and when coupled by gene flow, there is amplitude death of the oscillations in each deme. Numerical simulations show that for a multiple deme island model, costs of resistance and virulence need not to be present in each deme for stable polymorphism to occur. CONCLUSIONS: Our theoretical results confirm the importance of empirical studies for measuring the environmental heterogeneity for genetic costs of resistance and virulence alleles. We suggest that such studies should be developed to investigate the generality of this mechanism for the long term maintenance of genetic diversity at host and parasite genes. PMID- 22044633 TI - Genome-wide dynamic changes of DNA methylation of repetitive elements in human embryonic stem cells and fetal fibroblasts. AB - DNA methylation changes in repetitive elements (REs) are associated with the regulation of gene transcription, embryonic development, differentiation and carcinogenesis. However, genome-wide analysis of DNA methylation of human REs is lacking. Here, we performed genome-wide methylation analysis of REs in nine repeat types in human embryonic stem cells (H1) and fetal fibroblasts (IMR90), and found that the potential for changes in the DNA methylation of REs was different among the nine repeat types and within different genomic regions. DNA methylation changes in the nine repeat types were related to the GC content and CpG density of the sequence contexts. The differentially methylated REs and targeted genes of different repeat types were associated with gene silencing in the transition from H1 to IMR90 cells. Our results suggest that a quarter of REs are involved in the reprogramming of DNA methylation which may play important epigenetic roles during cellular differentiation. PMID- 22044634 TI - Projection to latent pathways (PLP): a constrained projection to latent variables (PLS) method for elementary flux modes discrimination. AB - BACKGROUND: Elementary flux modes (EFM) are unique and non-decomposable sets of metabolic reactions able to operate coherently in steady-state. A metabolic network has in general a very high number of EFM reflecting the typical functional redundancy of biological systems. However, most of these EFM are either thermodynamically unfeasible or inactive at pre-set environmental conditions. RESULTS: Here we present a new algorithm that discriminates the "active" set of EFM on the basis of dynamic envirome data. The algorithm merges together two well-known methods: projection to latent structures (PLS) and EFM analysis, and is therefore termed projection to latent pathways (PLP). PLP has two concomitant goals: (1) maximisation of correlation between EFM weighting factors and measured envirome data and (2) minimisation of redundancy by eliminating EFM with low correlation with the envirome. CONCLUSIONS: Overall, our results demonstrate that PLP slightly outperforms PLS in terms of predictive power. But more importantly, PLP is able to discriminate the subset of EFM with highest correlation with the envirome, thus providing in-depth knowledge of how the environment controls core cellular functions. This offers a significant advantage over PLS since its abstract structure cannot be associated with the underlying biological structure. PMID- 22044635 TI - Clinical indicators of bacterial meningitis among neonates and young infants in rural Kenya. AB - BACKGROUND: Meningitis is notoriously difficult to diagnose in infancy because its clinical features are non-specific. World Health Organization (WHO) guidelines suggest several indicative signs, based on limited data. We aimed to identify indicators of bacterial meningitis in young infants in Kenya, and compared their performance to the WHO guidelines. We also examined the feasibility of developing a scoring system for meningitis. METHODS: We studied all admissions aged < 60 days to Kilifi District Hospital, 2001 through 2005. We evaluated clinical indicators against microbiological findings using likelihood ratios. We prospectively validated our findings 2006 through 2007. RESULTS: We studied 2,411 and 1,512 young infants during the derivation and validation periods respectively. During derivation, 31/1,031 (3.0%) neonates aged < 7 days and 67/1,380 (4.8%) young infants aged 7-59 days (p < 0.001) had meningitis. 90% of cases could be diagnosed macroscopically (turbidity) or by microscopic leukocyte counting. Independent indicators of meningitis were: fever, convulsions, irritability, bulging fontanel and temperature >= 39 degrees C. Areas under the receiver operating characteristic curve in the validation period were 0.62 [95%CI: 0.49-0.75] age < 7 days and 0.76 [95%CI: 0.68-0.85] thereafter (P = 0.07), and using the WHO signs, 0.50 [95%CI 0.35-0.65] age < 7 days and 0.82 [95%CI: 0.75-0.89] thereafter (P = 0.0001). The number needed to LP to identify one case was 21 [95%CI: 15-35] for our signs, and 28 [95%CI: 18-61] for WHO signs. With a scoring system, a cut-off of >= 1 sign offered the best compromise on sensitivity and specificity. CONCLUSION: Simple clinical signs at admission identify two thirds of meningitis cases in neonates and young infants. Lumbar puncture is essential to diagnosis and avoidance of unnecessary treatment, and is worthwhile without CSF biochemistry or bacterial culture. The signs of Meningitis suggested by the WHO perform poorly in the first week of life. A scoring system for meningitis in this age group is not helpful. PMID- 22044636 TI - Exploring the biological basis of haemophilic joint disease: experimental studies. AB - Haemophilia has been recognized as the most severe among the inherited disorders of blood coagulation since the beginning of the first millennium. Joint damage is the hallmark of the disease. Despite its frequency and severity, the pathobiology of blood-induced joint disease remains obscure. Although bleeding into the joint is the ultimate provocation, the stimulus within the blood inciting the process and the mechanisms by which bleeding into a joint results in synovial inflammation (synovitis) and cartilage and bone destruction (arthropathy) is unknown. Clues from careful observation of patient material, supplemented with data from animal models of joint disease provide some clues as to the pathogenesis of the process. Among the questions that remain to be answered are the following: (i) What underlies the phenotypic variability in bleeding patterns of patients with severe disease and the development of arthropathy in some but not all patients with joint bleeding? (ii) What is the molecular basis underlying the variability? (iii) Are there strategies that can be developed to counter the deleterious effects of joint bleeding and prevent blood-induced joint disease? Understanding the key elements, genetic and/or environmental, that are necessary for the development of synovitis and arthropathy may lead to rational design of therapy for the targeted prevention and treatment of blood-induced joint disease. PMID- 22044637 TI - Benchmarks for flexible and rigid transcription factor-DNA docking. AB - BACKGROUND: Structural insight from transcription factor-DNA (TF-DNA) complexes is of paramount importance to our understanding of the affinity and specificity of TF-DNA interaction, and to the development of structure-based prediction of TF binding sites. Yet the majority of the TF-DNA complexes remain unsolved despite the considerable experimental efforts being made. Computational docking represents a promising alternative to bridge the gap. To facilitate the study of TF-DNA docking, carefully designed benchmarks are needed for performance evaluation and identification of the strengths and weaknesses of docking algorithms. RESULTS: We constructed two benchmarks for flexible and rigid TF-DNA docking respectively using a unified non-redundant set of 38 test cases. The test cases encompass diverse fold families and are classified into easy and hard groups with respect to the degrees of difficulty in TF-DNA docking. The major parameters used to classify expected docking difficulty in flexible docking are the conformational differences between bound and unbound TFs and the interaction strength between TFs and DNA. For rigid docking in which the starting structure is a bound TF conformation, only interaction strength is considered. CONCLUSIONS: We believe these benchmarks are important for the development of better interaction potentials and TF-DNA docking algorithms, which bears important implications to structure-based prediction of transcription factor binding sites and drug design. PMID- 22044638 TI - Node-positive renal cell carcinoma in the absence of distant metastases: predictors of cancer-specific mortality in a population-based cohort. AB - Nodal metastases, even in the absence of distant metastases, portend a bad prognosis. The percentage of positive nodes (PPN) represents an important predictor of cancer-specific mortality (CSM) in patients in the group T(any) N(1) M(0) . In consequence, universal inclusion of PPN should be considered in prospective and retrospective CSM analyses. OBJECTIVES: To examine the outcomes of patients with node-positive renal cell carcinoma (RCC) in the absence of distant metastases in a large population-based cohort of patients To examine the ability of standard risk factors to predict cancer-specific mortality (CSM). PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results database, a total of 799 patients with RCC nodal metastases and absence of distant metastases undergoing nephrectomy were identified. Univariable and multivariable analyses was performed with the aim of identifying independent predictors of CSM in this cohort of patients. Specifically, we examined the effect of the number of removed nodes (NRN), the number of positive nodes (NPN) and the percentage of positive nodes (PPN) on CSM. RESULTS: Actuarial survival estimates showed that 53.2, 37.8 and 25.7% of patients survived at 24, 60 and 120 months after nephrectomy. In Kaplan-Meier analyses, NRN failed to clearly discriminate between recorded CSM rates (log rank P = 0.07). Discrimination was noted when CSM was stratified according to NPN (log rank P = 0.02) and PPN (log rank P = 0.001). In multivariable analyses, age, Fuhrman grade, histological subtype, T stage and PPN were independent predictors of CSM. CONCLUSIONS: Our data indicate that CSM of patients with exclusive nodal metastases differs according to PPN. Consequently, PPN warrants consideration in future prognostic schemes. PMID- 22044639 TI - Left atrial metastases of poorly differentiated thyroid carcinoma diagnosed by echocardiography and magnetic resonance imaging--case report and review of literature. AB - Intracardiac metastases of thyroid carcinoma are a rare event. Their incidence is low in large autopsy series, and antemortem diagnosis is even less common. We present the case of a woman with advanced poorly differentiated thyroid carcinoma who had extensive intracardiac metastases. This case highlights the usefulness of echocardiography and magnetic resonance imaging in the diagnosis and differential diagnosis of cardiac metastases. PMID- 22044640 TI - Further improvements on the factors affecting bone mineral density measured by quantitative micro-computed tomography. AB - The effects of imaging parameters and special configuration of objects within the reconstruction space on the micro computed tomography (MUCT) based mineral density have been explored, and a series of density correction curves have been presented. A manufacturer-provided calibration phantom (0, 100, 200, 400, 800 mg HA/cm(3)) was imaged at all possible imaging conditions (n=216) based on energy, resolution, vial diameter, beam hardening correction factor and averaging. For each imaging condition, a linear regression model was fitted to the observed versus expected densities, and the intercepts (beta(0)) and slopes (beta(1)) of the regression lines and each density level were modeled using multiple regression modeling. Additionally, a custom made phantom (0, 50, 150, 500, 800, 1000 and 1500 mg HA/cm(3)) was scanned in order to study the effects of location and orientation of an object within the reconstruction space and presence of surrounding objects on MUCT based mineral density. The energy, vial diameter and beam hardening correction factor were significant predictors of cumineral density (P values<0.001), while averaging and resolution did not have a significant effect on the observed density values (P values>0.1) except for 0.0 density (P values<0.04). Varying the location of an object within the reconstruction space from the center to the periphery resulted in a drop in observed mineral density up to 10% (P values<0.005). The presence of surrounding densities resulted in decreased observed mineral density up to 17% at the center and up to 14% at the periphery of the reconstruction space (P values<0.001 for all densities). Changing the orientation of the sample also had a significant effect on the observed mineral density, resulting in up to 16% lower observed mineral density for vertical vs. horizontal orientation at the center of the reconstruction space (P value<0.001). We conclude that energy, resolution and post processing correction factor are significant predictors of the observed mineral density in MUCT. PMID- 22044642 TI - The influence of systemic therapy on the serum levels of IL-6 and IL-8 in pemphigus vulgaris. AB - BACKGROUND: The place of cell-mediated immunity and cytokines in the immunopathogenesis of pemphigus vulgaris (PV) has not been fully established. OBJECTIVE: To assess the serum levels of pro-inflammatory cytokines, Interleukine 6 (IL-6) and Interleukine-8 (IL-8), in PV patients before and after therapy, to evaluate the influence of therapy on the serum cytokine levels. METHODS: Sixty six newly diagnosed PV patients enrolled into the study. The serum levels of IL-8 and IL-6 were measured in 66 and 64 patients, respectively. According to the extent of skin and mucosal involvement, the patients were divided into two groups namely mild and severe. The serum levels of cytokines were measured using enzyme linked immunosorbent assay (ELISA) method before and after 4 weeks of prednisolone plus azathioprine therapy. RESULTS: In 64 patients studied for the serum level of IL-6, the median IL-6 level was significantly decreased from 1.6 to 0.9 pg/mL by therapy (P-value = 0.001). Segregating the patients according to the severity of the disease, the serum level of IL-6 did not differ significantly by therapy in patients with a mild disease. However, in patients with a severe disease the median serum level of IL-6 decreased significantly from 1.8 to 0.9 pg/mL after therapy (P-value = 0.001). No significant changes were found in the IL-8 level by treatment. CONCLUSION: The significant decrease in the IL-6 level after therapy suggests that blocking of IL-6 could have therapeutic benefits for the treatment of PV, particularly in severe forms. PMID- 22044641 TI - Bacterial communities in sediments of the shallow Lake Dongping in China. AB - AIMS: The purpose of this study was to discuss how the environmental inputs and anthropogenic activities impact bacterial communities in the sediments of a shallow, eutrophic and temperate freshwater lake. METHODS AND RESULTS: Sediment cores were collected from Lake Dongping, located in Taian, Shandong, China. All samples were processed within 4 h of collection. Total nitrogen, total phosphorus (TP), total organic carbon, ammonium nitrogen and nitrate nitrogen content of samples were measured by Kjeldahl determination, sulphuric acid-perchloric acid digestion and molybdenum blue colorimetry, potassium dichromate titration, Nessler's reagent colorimetric and the phenol disulphonic acid colorimetric method, respectively. Seasonal and temporal diversity of sediment bacterial communities at six stations in Lake Dongping were investigated using molecular approaches (terminal restriction fragment length polymorphism and 16S rDNA clone libraries). Noticeable seasonal and temporal variations were observed in bacterial diversity and composition at all six stations. Sediment bacterial communities in Lake Dongping belonged to 16 phyla: Proteobacteria (including alpha-Proteobacteria, beta-Proteobacteria, delta-Proteobacteria, epsilon Proteobacteria, gamma-Proteobacteria), Acidobacteria, Planctomycetes, Bacteroidetes, Firmicutes, Verrucomicrobia, Nitrospira, Chloroflexi, Gemmatimonadetes, Chlorobi, Cyanobacteria, Deferribacteres, Actinobacteria, OP8, Spirochaetes and OP11. Members of beta-, delta- and gamma-Proteobacterial sequences were predominant in 11 of 12 clone libraries derived from sediment samples. Sediment samples collected at stations 1 and 4 in July had the greatest bacterial diversity while those collected at station 2 in October had the least diversity. TP concentration was significantly correlated with the distribution of bacterial communities. CONCLUSIONS: Our results suggested that different environmental nutrient inputs contribute to seasonal and temporal variations of chemical features and bacterial communities in sediments of Lake Dongping. TP concentration was significantly correlated with the distribution of bacterial communities. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has an important implication for the optimization of integrated ecosystem assessment of shallow temperate freshwater lake and provides interesting information for the subsequent of the ecosystem. PMID- 22044643 TI - Assessing the impact of a Christmas advertisement campaign on Catalan wine preference using Choice Experiments. AB - Our paper seeks to assess the impact of information and advertisement on consumers' preference for wines in special occasions (Christmas) in Catalonia (Spain). We apply the Choice Experiments method to study the relative importance of attributes that describe consumers' decision to purchase wine by using the Heteroskedastic Extreme Value (HEV) model. Data were obtained from two questionnaires applied to a pre and post spot samples formed by 299 and 400 individuals, respectively. Results suggest that the proposed spot does not affect the ranking of the preferred attributes, nevertheless this preference is heterogeneous. After advertising preferences scores have revealed significant differences. The relative importance of the "Catalan" wine has increased compared to the "Spanish" wine. The most preferred product is a Catalan wine made from the "Cabernet Sauvignon" variety. Wines that have been previously tasted by the consumer seem to be preferred over recommended or prestigious wines. However, advertising increases the relative importance of prestigious wines. PMID- 22044645 TI - Expression of platelet-bound stromal cell-derived factor-1 in patients with non valvular atrial fibrillation and ischemic heart disease. AB - AIMS: Blood cell infiltration and inflammation are involved in atrial remodelling during atrial fibrillation (AF) although the exact mechanisms of inflammatory cell recruitment remain poorly understood. Platelet-bound stromal cell-derived factor-1 (SDF-1) is increased in cases of ischemic myocardium and regulates recruitment of CXCR4(+) cells on the vascular wall. Whether platelet-bound SDF-1 expression is differentially influenced by non-valvular paroxysmal or permanent atrial fibrillation (AF) in patients with stable angina pectoris (SAP) or acute coronary syndrome (ACS) has not been reported so far. METHODS AND RESULTS: A total of 1291 consecutive patients with coronary artery disease (CAD) undergoing coronary angiography were recruited. Among the patients with SAP, platelet-bound SDF-1 is increased in patients with paroxysmal AF compared with SR or to persistent/permanent AF (P < 0.05 for both). Platelet-bound SDF-1 correlated with plasma SDF-1 (r = 0.488, P = 0.013) in patients with AF and ACS, which was more pronounced among patients with persistent AF (r = 0.842, P = 0.009). Plasma SDF-1 was increased in persistent/permanent AF compared with SR. Patients with ACS presented with enhanced platelet-bound-SDF-1 compared with SAP. Interestingly, among patients with ACS, patients with paroxysmal or persistent/permanent AF presented with an impaired platelet-bound SDF-1 expression compared with patients with SR. CONCLUSIONS: Differential expression of platelet-bound and plasma SDF-1 was observed in patients with AF compared with SR which may be involved in progenitor cell mobilization and inflammatory cell recruitment in patients with AF and ischemic heart disease. Further in vivo studies are required to elucidate the role of SDF-1 in atrial remodeling and the atrial fibrillation course. PMID- 22044644 TI - Plasma proteomic profiles from disease-discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases. AB - INTRODUCTION: Although systemic autoimmune diseases (SAID) share many clinical and laboratory features, whether they also share some common features of pathogenesis remains unclear. We assessed plasma proteomic profiles among different SAID for evidence of common molecular pathways that could provide insights into pathogenic mechanisms shared by these diseases. METHODS: Differential quantitative proteomic analyses (one-dimensional reverse-phase liquid chromatography-mass spectrometry) were performed to assess patterns of plasma protein expression. Monozygotic twins (four pairs discordant for systemic lupus erythematosus, four pairs discordant for juvenile idiopathic arthritis and two pairs discordant for juvenile dermatomyositis) were studied to minimize polymorphic gene effects. Comparisons were also made to 10 unrelated, matched controls. RESULTS: Multiple plasma proteins, including acute phase reactants, structural proteins, immune response proteins, coagulation and transcriptional factors, were differentially expressed similarly among the different SAID studied. Multivariate Random Forest modeling identified seven proteins whose combined altered expression levels effectively segregated affected vs. unaffected twins. Among these seven proteins, four were also identified in univariate analyses of proteomic data (syntaxin 17, alpha-glucosidase, paraoxonase 1, and the sixth component of complement). Molecular pathway modeling indicated that these factors may be integrated through interactions with a candidate plasma biomarker, PON1 and the pro-inflammatory cytokine IL-6. CONCLUSIONS: Together, these data suggest that different SAID may share common alterations of plasma protein expression and molecular pathways. An understanding of the mechanisms leading to the altered plasma proteomes common among these SAID may provide useful insights into their pathogeneses. PMID- 22044646 TI - Meta-analysis of susceptibility of woody plants to loss of genetic diversity through habitat fragmentation. AB - Shrubs and trees are assumed less likely to lose genetic variation in response to habitat fragmentation because they have certain life-history characteristics such as long lifespans and extensive pollen flow. To test this assumption, we conducted a meta-analysis with data on 97 woody plant species derived from 98 studies of habitat fragmentation. We measured the weighted response of four different measures of population-level genetic diversity to habitat fragmentation with Hedge's d and Spearman rank correlation. We tested whether the genetic response to habitat fragmentation was mediated by life-history traits (longevity, pollination mode, and seed dispersal vector) and study characteristics (genetic marker and plant material used). For both tests of effect size habitat fragmentation was associated with a substantial decrease in expected heterozygosity, number of alleles, and percentage of polymorphic loci, whereas the population inbreeding coefficient was not associated with these measures. The largest proportion of variation among effect sizes was explained by pollination mechanism and by the age of the tissue (progeny or adult) that was genotyped. Our primary finding was that wind-pollinated trees and shrubs appeared to be as likely to lose genetic variation as insect-pollinated species, indicating that severe habitat fragmentation may lead to pollen limitation and limited gene flow. In comparison with results of previous meta-analyses on mainly herbaceous species, we found trees and shrubs were as likely to have negative genetic responses to habitat fragmentation as herbaceous species. We also found that the genetic variation in offspring was generally less than that of adult trees, which is evidence of a genetic extinction debt and probably reflects the genetic diversity of the historical, less-fragmented landscape. PMID- 22044647 TI - Attention in action: evidence from on-line corrections in left visual neglect. AB - It is widely accepted that the posterior parietal cortex is critical for the on line control of action and optic ataxia patients are unable to correct their movements in-flight to changes in target position. The current study investigated on-line correction in patients with left visual neglect, right brain damaged patients without neglect and healthy controls. Participants were asked to reach towards a central target that could jump unexpectedly, at movement onset, to the right or left sides of space. In response to the jump, participants were asked either to follow the target or to stop their movement. Neglect patients were able to correct their ongoing movements smoothly and accurately towards right and left target jumps. They did so even when told to stop their movement, indicating that these corrections occurred automatically (i.e., without instruction). However, the timing of corrections to the left was delayed in neglect patients and this produced a drastic increase in movement time. To our surprise, we also found that neglect patients were impaired at stopping their ongoing reaches, when compared to the control groups, in response to either left or right jump trials. We suggest that the 'automatic pilot' system for the hand is spared in neglect, but its processing speed is unilaterally slowed due to a deficit in orienting of attention to the contralesional side. We relate these findings to the breakdown of a system that combines information for attention, perception and action. Damage to this system may not only slow corrective movements to the contralesional side, but also produce non-lateralized deficits in interrupting an ongoing reach. PMID- 22044648 TI - A "concrete view" of aging: event related potentials reveal age-related changes in basic integrative processes in language. AB - Normal aging is accompanied by changes in both structural and functional cerebral organization. Although verbal knowledge seems to be relatively stable across the lifespan, there are age-related changes in the rapid use of that knowledge during on-line language processing. In particular, aging has been linked to reduce effectiveness in preparing for upcoming words and building an integrated sentence level representation. The current study assessed whether such age-related changes extend even to much simpler language units, such as modification relations between a centrally presented adjective and a lateralized noun. Adjectives were used to elicit concrete and abstract meanings of the same, polysemous lexical items (e.g., "green book" vs. "interesting book"). Consistent with findings that lexical information is preserved with age, older adults, like younger adults, exhibited concreteness effects at the adjectives, with more negative responses to concrete adjectives over posterior (300-500 ms; N400) and frontal (300-900 ms) channels. However, at the noun, younger adults exhibited concreteness-based predictability effects linked to left hemisphere processing and imagery effects linked to right hemisphere processing, contingent on whether the adjectives and nouns formed a cohesive conceptual unit. In contrast, older adults showed neither effect, suggesting that they were less able to rapidly link the adjective-noun meaning to form an integrated conceptual representation. Age-related changes in language processing may thus be more pervasive than previously realized. PMID- 22044649 TI - Nouns referring to tools and natural objects differentially modulate the motor system. AB - While increasing evidence points to a critical role for the motor system in language processing, the focus of previous work has been on the linguistic category of verbs. Here we tested whether nouns are effective in modulating the motor system and further whether different kinds of nouns - those referring to artifacts or natural items, and items that are graspable or ungraspable - would differentially modulate the system. A Transcranial Magnetic Stimulation (TMS) study was carried out to compare modulation of the motor system when subjects read nouns referring to objects which are Artificial or Natural and which are Graspable or Ungraspable. TMS was applied to the primary motor cortex representation of the first dorsal interosseous (FDI) muscle of the right hand at 150 ms after noun presentation. Analyses of Motor Evoked Potentials (MEPs) revealed that across the duration of the task, nouns referring to graspable artifacts (tools) were associated with significantly greater MEP areas. Analyses of the initial presentation of items revealed a main effect of graspability. The findings are in line with an embodied view of nouns, with MEP measures modulated according to whether nouns referred to natural objects or artifacts (tools), confirming tools as a special class of items in motor terms. Additionally our data support a difference for graspable versus non graspable objects, an effect which for natural objects is restricted to initial presentation of items. PMID- 22044650 TI - Effects of transcranial direct current stimulation (tDCS) on behaviour and electrophysiology of language production. AB - Excitatory anodal transcranial direct current stimulation (A-tDCS) over the left dorsal prefrontal cortex (DPFC) has been shown to improve language production. The present study examined neurophysiological underpinnings of this effect. In a single-blinded within-subject design, we traced effects of A-tDCS compared to sham stimulation over the left DPFC using electrophysiological and behavioural correlates during overt picture naming. Online effects were examined during A tDCS by employing the semantic interference (SI-)Effect - a marker that denotes the functional integrity of the language system. The behavioural SI-Effect was found to be reduced, whereas the electrophysiological SI-Effect was enhanced over left compared to right temporal scalp-electrode sites. This modulation is suggested to reflect a superior tuning of neural responses within language related generators. After -(offline) effects of A-tDCS were detected in the delta frequency band, a marker of neural inhibition. After A-tDCS there was a reduction in delta activity during picture naming and the resting state, interpreted to indicate neural disinhibition. Together, these findings demonstrate electrophysiological modulations induced by A-tDCS of the left DPFC. They suggest that A-tDCS is capable of enhancing neural processes during and after application. The present functional and oscillatory neural markers could detect positive effects of prefrontal A-tDCS, which could be of use in the neuro rehabilitation of frontal language functions. PMID- 22044651 TI - Working memory and amnesia: the role of stimulus novelty. AB - Despite the traditional view that damage to the hippocampus and/or surrounding areas of the medial temporal lobe (MTL) does not impair short-term or working memory (WM), recent research has shown MTL amnesics to be impaired on WM tasks that require maintaining a small amount of information over brief retention intervals (e.g., maintenance of a single face for one second). However, the types of tasks that have demonstrated WM impairments in amnesia tend to have involved novel stimuli. We hypothesized that WM may be impaired in amnesia for tasks that require maintaining novel information, but may be preserved for more familiar material, particularly if the material can be easily rehearsed. To test this hypothesis, patient HC, a 22-year-old developmental amnesic with relatively preserved semantic memory and 20 age and education matched controls performed a delayed match-to-sample task that required maintaining a single famous or non famous face for 1-8s, digit span and reading span tasks, and a modified Brown Peterson task that required maintaining a single high- or low-frequency word or a non-word for 4-8s. HC's performance was impaired for non-famous faces but preserved for famous faces, impaired for the reading span task but preserved for digit span, and it was impaired for non-words and unfamiliar low-frequency words but preserved for familiar words. These results support the hypothesis that an intact hippocampus is necessary for maintaining a single novel stimulus in WM. However, stimulus familiarity and rehearsal support WM via cortical regions independent of the MTL. PMID- 22044652 TI - Regulation of the actin cytoskeleton in Helicobacter pylori-induced migration and invasive growth of gastric epithelial cells. AB - Dynamic rearrangement of the actin cytoskeleton is a significant hallmark of Helicobacter pylori (H. pylori) infected gastric epithelial cells leading to cell migration and invasive growth. Considering the cellular mechanisms, the type IV secretion system (T4SS) and the effector protein cytotoxin-associated gene A (CagA) of H. pylori are well-studied initiators of distinct signal transduction pathways in host cells targeting kinases, adaptor proteins, GTPases, actin binding and other proteins involved in the regulation of the actin lattice. In this review, we summarize recent findings of how H. pylori functionally interacts with the complex signaling network that controls the actin cytoskeleton of motile and invasive gastric epithelial cells. PMID- 22044653 TI - Sleep in children and adolescents with Angelman syndrome: association with parent sleep and stress. AB - BACKGROUND: Sleep concerns are common in children with Angelman syndrome, with 20 80% of individuals having a decreased sleep need and/or abnormal sleep-wake cycles. The impact of these sleep behaviours on parental sleep and stress is not known. METHOD: Through the use of standardised questionnaires, wrist actigraphy and polysomnography, we defined the sleep behaviours of 15 children/adolescents with Angelman syndrome and the association of the child/adolescents sleep behaviours on parental sleep behaviours and parental stress. RESULTS: Both children/adolescents and their parents exhibited over 1 h of wake time after sleep onset and fragmented sleep. Prolonged sleep latency in the child was associated with parent insomnia and daytime sleepiness. Additionally, variability in child total sleep time was associated with parental stress. CONCLUSIONS: Poor sleep in children/adolescents with Angelman syndrome was associated with poor parental sleep and higher parental stress. Further work is warranted to identify the underlying causes of the poor sleep, and to relate these findings to daytime functioning, behaviour and the family unit. PMID- 22044654 TI - Optic disc haemorrhage and posterior vitreous haemorrhage from an acute posterior vitreous detachment. PMID- 22044655 TI - A focus on shoulders. PMID- 22044656 TI - Synthesis and in vitro evaluation of analogues of avocado-produced toxin (+)-(R) persin in human breast cancer cells. AB - A structure-activity study of several new synthetic analogues of the avocado produced toxin persin has been conducted, with compounds being evaluated for their cytostatic and pro-apoptotic effects in human breast cancer cells. A 4 pyridinyl derivative demonstrated activity comparable to that of the natural product, suggesting future directions for exploration of structure-activity relationships. PMID- 22044657 TI - Diversity of metalloproteinases in Bothrops neuwiedi snake venom transcripts: evidences for recombination between different classes of SVMPs. AB - BACKGROUND: Snake venom metalloproteinases (SVMPs) are widely distributed in snake venoms and are versatile toxins, targeting many important elements involved in hemostasis, such as basement membrane proteins, clotting proteins, platelets, endothelial and inflammatory cells. The functional diversity of SVMPs is in part due to the structural organization of different combinations of catalytic, disintegrin, disintegrin-like and cysteine-rich domains, which categorizes SVMPs in 3 classes of precursor molecules (PI, PII and PIII) further divided in 11 subclasses, 6 of them belonging to PII group. This heterogeneity is currently correlated to genetic accelerated evolution and post-translational modifications. RESULTS: Thirty-one SVMP cDNAs were full length cloned from a single specimen of Bothrops neuwiedi snake, sequenced and grouped in eleven distinct sequences and further analyzed by cladistic analysis. Class P-I and class P-III sequences presented the expected tree topology for fibrinolytic and hemorrhagic SVMPs, respectively. In opposition, three distinct segregations were observed for class P-II sequences. P-IIb showed the typical segregation of class P-II SVMPs. However, P-IIa grouped with class P-I cDNAs presenting a 100% identity in the 365 bp at their 5' ends, suggesting post-transcription events for interclass recombination. In addition, catalytic domain of P-IIx sequences segregated with non-hemorrhagic class P-III SVMPs while their disintegrin domain grouped with other class P-II disintegrin domains suggesting independent evolution of catalytic and disintegrin domains. Complementary regions within cDNA sequences were noted and may participate in recombination either at DNA or RNA levels. Proteins predicted by these cDNAs show the main features of the correspondent classes of SVMP, but P-IIb and P-IIx included two additional cysteines cysteines at the C-termini of the disintegrin domains in positions not yet described. CONCLUSIONS: In B. neuwiedi venom gland, class P-II SVMPs were represented by three different types of transcripts that may have arisen by interclass recombination with P-I and P-III sequences after the divergence of the different classes of SVMPs. Our observations indicate that exon shuffling or post transcriptional mechanisms may be driving these recombinations generating new functional possibilities for this complex group of snake toxins. PMID- 22044658 TI - Pulmonary complications of pneumococcal community-acquired pneumonia: incidence, predictors, and outcomes. AB - The aim of this study was to evaluate the clinical characteristics, predictors and outcomes of pneumococcal pneumonia developing pulmonary complications and the distribution of pneumococcal serotypes. It was a prospective study including all adult patients admitted to the Hospital Clinic of Barcelona, Spain (2001-2009) with the diagnosis of pneumococcal pneumonia. Microbiological investigation was systematically performed, including antimicrobial susceptibility and serotype distribution (only invasive strains isolated during 2006-2009). Complicated pneumonia was defined as the presence of one or more pulmonary complications: pleural effusion, empyema, or multilobar infiltrates. We included 626 patients, and 235 (38%) had the following pulmonary complications: pleural effusion, 122 (52%); empyema, 18 (8%); and multilobar infiltration, 151 (64%). Forty-six (20%) patients had more than one complication. Patients with pulmonary complications showed a higher rate of intensive-care unit admission (34% vs. 13%, p <0.001), a higher rate of shock (16% vs. 7%, p <0.001), a longer length of stay (9 days vs. 6 days, p <0.001), and a lower rate of penicillin resistance (14% vs. 25%, p 0.013), but similar mortality (9% vs. 8%). No significant differences were observed in the serotype distribution between complicated and uncomplicated pneumonia. Chronic obstructive pulmonary disease (COPD) (OR 0.38, 95% CI 0.23 0.63; p <0.001) was a protective factor against pulmonary complications, whereas chronic liver disease (OR 3.60, 95% CI 1.71-7.60; p 0.001), admission C-reactive protein level >=18 mg/dL (OR 2.77, 95% CI 1.91-4.00; p <0.001) and admission creatinine level >1.5 mg/dL (OR 2.01, 95% CI 1.31-3.08; p 0.001) were risk factors for pulmonary complications. Complicated pneumonia was characterized by a more severe clinical presentation, but was not associated with increased mortality. Resistance to antibiotics was lower in complicated cases. No significant differences were observed in the serotype distribution between complicated and uncomplicated pneumonia. In the multivariate analysis, COPD was a protective factor against pulmonary complications. PMID- 22044659 TI - Effects of intracellular superoxide removal at acupoints with TAT-SOD on obesity. PMID- 22044660 TI - Association between 8-oxo-7,8-dihydroguanine excretion and risk of lung cancer in a prospective study. AB - Oxidative damage to guanine (8-oxoGua) is one of the most abundant lesions induced by oxidative stress and documented mutagenic. 8-Oxoguanine DNA glycosylase 1 (OGG1) removes 8-oxoGua from DNA by excision. The urinary excretion of 8-oxoGua is a biomarker of exposure, reflecting the rate of damage in the steady state. The aim of this study was to investigate urinary 8-oxoGua as a risk factor for lung cancer. In a nested case-cohort design we examined associations between urinary excretion of 8-oxoGua and risk of lung cancer as well as potential interaction with the OGG1 Ser326Cys polymorphism in a population-based cohort of 25,717 men and 27,972 women aged 50-64 years with 3-7 years follow-up. We included 260 cases with lung cancer and a subcohort of 263 individuals matched on sex, age, and smoking duration for comparison. Urine collected at entry was analysed for 8-oxoGua by HPLC with electrochemical detection. There was no significant effect of smoking or OGG1 genotype on the excretion of 8-oxoGua. Overall the incidence rate ratio (IRR) (95% confidence interval) of lung cancer was 1.06 (0.97-1.15) per doubling of 8-oxoGua excretion. The association between lung cancer risk and 8-oxoGua excretion was significant among men [IRR: 1.17 (1.03-1.31)], never-smokers [IRR: 9.94 (1.04-94.7)], and former smokers [IRR: 1.19 (1.07-1.33)]. There was no significant interaction with the OGG1 genotype, although the IRR was 1.14 (0.98-1.34) among subjects homozygous for Cys326. The association between urinary 8-oxoGua excretion and lung cancer risk among former and never-smokers suggests that oxidative stress with damage to DNA is important in this group. PMID- 22044661 TI - Effect of 12 months of testosterone replacement therapy on metabolic syndrome components in hypogonadal men: data from the Testim Registry in the US (TRiUS). AB - BACKGROUND: Recent evidence suggests that there may be a bidirectional, physiological link between hypogonadism and metabolic syndrome (MetS), and testosterone replacement therapy (TRT) has been shown to improve some symptoms of MetS in small patient populations. We examined the effect of 12 months of TRT on MetS components in a large cohort of hypogonadal men. METHODS: Data were obtained from TRiUS (Testim(r) Registry in the United States), a 12-month, multicenter, prospective observational registry (N = 849) of hypogonadal men prescribed Testim 1% testosterone gel (5-10 g/day). Data analyzed included age, total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), and MetS components: waist circumference, blood pressure, fasting blood glucose, plasma triglycerides, and HDL cholesterol. RESULTS: Of evaluable patients (581/849) at baseline, 37% were MetS+ (n = 213) and 63% were MetS- (n = 368). MetS+ patients had significantly lower TT (p < 0.0001) and SHBG (p = 0.01) levels. Patients with the lowest quartile TT levels (<206 ng/dL [<7.1 nmol/L]) had a significantly increased risk of MetS+ classification vs those with highest quartile TT levels (>=331 ng/dL [>=11.5 nmol/L]) (odds ratio 2.66; 95% CI, 1.60 to 4.43). After 12 months of TRT, TT levels significantly increased in all patients (p < 0.005). Despite having similar TT levels after TRT, only MetS+ patients demonstrated significant decreases in waist circumference, fasting blood glucose levels, and blood pressure; lowest TT quartile patients demonstrated significant decreases in waist circumference and fasting blood glucose. Neither HDL cholesterol nor triglyceride levels changed significantly in either patient population. CONCLUSION: Hypogonadal MetS+ patients were more likely than their MetS- counterparts to have lower baseline TT levels and present with more comorbid conditions. MetS+ patients and those in the lowest TT quartile showed improvement in some metabolic syndrome components after 12 months of TRT. While it is currently unclear if further cardiometabolic benefit can be seen with longer TRT use in this population, testing for low testosterone may be warranted in MetS+ men with hypogonadal symptoms. PMID- 22044662 TI - Healthcare resource utilization among haemophilia A patients in the United States. AB - Advances in therapy have improved life expectancy and quality of life of patients with haemophilia A. Due to the chronic and complex management of this disease, particularly, the development of inhibitors, little is known about their health resource utilization in the real-life setting over time. The aim was to assess the distribution and trend of healthcare resource utilization among US haemophilia A patients with and without inhibitors. The MarketScan(r) Database, was queried to identify individuals with >=1 year continuous enrolment, two medical diagnoses of haemophilia A and claims for factor VIII or bypassing agent (to infer inhibitor status) during 2001-2007. Haemophilia-related cost was estimated from inpatient, outpatient and pharmacy claims. Annual cost differences were assessed by age and over a 4-year period for those with continuous enrolment. Among 51 million covered lives, 1044 haemophilia patients were identified, of whom 981 (94%; mean age = 21.2 years) did not have an inhibitor. The median haemophilia-related cost for these patients was $63,935 per patient per year. When normalized by weight, annual cost was stable (no statistically significant differences) among 312 non-inhibitor patients (mean age = 21.8 years) with 4-year continuous data. While there was a wide distribution of haemophilia related cost among the 63 individuals with an inhibitor (mean age = 15.4 years), only 0.6% of the total haemophilia patients had costs exceeding $1 million per patient per year. This study indicated that most haemophilia A patients were inhibitor-free with relatively stable annual costs over time. There was a wide distribution of haemophilia-related cost for inhibitor patients, while the proportion of patients who incurred extreme high cost was low. PMID- 22044663 TI - Outcomes of clomiphene citrate treatment in young hypogonadal men. AB - Study Type - Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Hypogonadism is a prevalent problem, increasing in frequency as men age. It is most commonly treated by testosterone supplementation therapy but in younger patients this can lead to testicular atrophy with subsequent exogenous testosterone dependency and may impair spermatogenesis. Clomiphene citrate (CC) may be used as an alternative treatment in these patients with hypogonadism when maintenance of fertility is desired. This study shows that CC is a safe and efficacious drug to use as an alternative to exogenous testosterone. Not only have we validated previous findings of other papers but have proven our findings over a much longer period (mean duration of treatment 19 months). This prospective study is the largest to date assessing both the objective hormone response to CC therapy as well as the subjective response based on a validated questionnaire. OBJECTIVE: * To prospectively assess the andrological outcomes of long-term clomiphene citrate (CC) treatment in hypogonadal men. PATIENTS AND METHODS: * We prospectively evaluated 86 men with hypogonadism (HG) as confirmed by two consecutive early morning testosterone measurements <300 ng/dL. * The cohort included all men with HG presenting to our clinic between 2002 and 2006 who, after an informed discussion, elected to have CC therapy. CC was commenced at 25 mg every other day and titrated to 50 mg every other day. The target testosterone level was 550 +/- 50 ng/dL. * Testosterone (free and total), sex hormone binding globulin, oestradiol, luteinizing hormone and follicle stimulating hormone were measured at baseline and during treatment on all patients. Once the desired testosterone level was achieved, testosterone/gonadotropin levels were measured twice per year. * To assess subjective response to treatment, the androgen deficiency in aging males (ADAM) questionnaire was administered before treatment and during follow-up. RESULTS: * Patients' mean (standard deviation [sd]; range) age was 29 (3; 22-37) years. Infertility was the most common reason (64%) for seeking treatment. The mean (sd) duration of CC treatment was 19 (14) months. * At the last evaluation, 70% of men were using 25 mg CC every other day, and the remainder were using 50 mg every other day. * All mean testosterone and gonadotropin measurements significantly increased during treatment. * Subjectively, there was an improvement in all questions (except loss of height) on the ADAM questionnaire. More than half the patients had an improvement in at least three symptoms. * There were no major side effects recorded and the presence of a varicocele did not have an impact on the response to CC. CONCLUSION: * Long-term follow-up of CC treatment for HG shows that it appears to be an effective and safe alternative to testosterone supplementation in men wishing to preserve their fertility. PMID- 22044664 TI - The evolution of metabolic networks of E. coli. AB - BACKGROUND: Despite the availability of numerous complete genome sequences from E. coli strains, published genome-scale metabolic models exist only for two commensal E. coli strains. These models have proven useful for many applications, such as engineering strains for desired product formation, and we sought to explore how constructing and evaluating additional metabolic models for E. coli strains could enhance these efforts. RESULTS: We used the genomic information from 16 E. coli strains to generate an E. coli pangenome metabolic network by evaluating their collective 76,990 ORFs. Each of these ORFs was assigned to one of 17,647 ortholog groups including ORFs associated with reactions in the most recent metabolic model for E. coli K-12. For orthologous groups that contain an ORF already represented in the MG1655 model, the gene to protein to reaction associations represented in this model could then be easily propagated to other E. coli strain models. All remaining orthologous groups were evaluated to see if new metabolic reactions could be added to generate a pangenome-scale metabolic model (iEco1712_pan). The pangenome model included reactions from a metabolic model update for E. coli K-12 MG1655 (iEco1339_MG1655) and enabled development of five additional strain-specific genome-scale metabolic models. These additional models include a second K-12 strain (iEco1335_W3110) and four pathogenic strains (two enterohemorrhagic E. coli O157:H7 and two uropathogens). When compared to the E. coli K-12 models, the metabolic models for the enterohemorrhagic (iEco1344_EDL933 and iEco1345_Sakai) and uropathogenic strains (iEco1288_CFT073 and iEco1301_UTI89) contained numerous lineage-specific gene and reaction differences. All six E. coli models were evaluated by comparing model predictions to carbon source utilization measurements under aerobic and anaerobic conditions, and to batch growth profiles in minimal media with 0.2% (w/v) glucose. An ancestral genome-scale metabolic model based on conserved ortholog groups in all 16 E. coli genomes was also constructed, reflecting the conserved ancestral core of E. coli metabolism (iEco1053_core). Comparative analysis of all six strain specific E. coli models revealed that some of the pathogenic E. coli strains possess reactions in their metabolic networks enabling higher biomass yields on glucose. Finally the lineage-specific metabolic traits were compared to the ancestral core model predictions to derive new insight into the evolution of metabolism within this species. CONCLUSION: Our findings demonstrate that a pangenome-scale metabolic model can be used to rapidly construct additional E. coli strain-specific models, and that quantitative models of different strains of E. coli can accurately predict strain-specific phenotypes. Such pangenome and strain-specific models can be further used to engineer metabolic phenotypes of interest, such as designing new industrial E. coli strains. PMID- 22044665 TI - Epidemiology and cost of herpes zoster and postherpetic neuralgia among patients treated in primary care centres in the Valencian community of Spain. AB - BACKGROUND: Data on the epidemiology and costs related to herpes zoster (HZ) and postherpetic neuralgia (PHN) in Spain are scarce; therefore, studies are needed to evaluate the epidemiological and economic impact of HZ and its most common complication, PHN. The present study aimed to estimate the clinical and economic burden of HZ and PHN in Valencia (Spain). METHODS: We prospectively analyzed the burden of HZ and PHN and their attributable costs in patients from 25 general practices in the Autonomous Community of Valencia serving 36,030 persons aged > 14 years. All patients with a clinical diagnosis of HZ who attended these centers between December 1st 2006 and November 30th 2007 were asked to participate. Patients included were followed for 1 year. RESULTS: Of the 130 cases of HZ followed up, continued pain was experienced by 47.6% (95% confidence interval (CI) = 35.6-56.7%) at 1 month after rash onset, by 14.5% (95% CI = 7.8-1.2%) at 3 months, by 9.0% (95% CI = 3.7-14.3%) at 6 months, and by 5.9% (95% CI = 1.5 10.3%) at 12 months. The percentage of patients with PHN increased with age, from 21.4% (95% CI = 8.3-40) in patients < 50 years to 59.2% (95% CI = 44.4-74) in patients >= 70 years. The estimated total cost for the 130 HZ cases during the follow-up period was ?49,160 ($67,349). Mean cost per patient was ?378 (range 53 2,830) ($517, range 73-3,877). CONCLUSIONS: This study shows that PHN is a relatively common complication of HZ and that both conditions combined give rise to a significant clinical and economic burden for patients and providers. PMID- 22044666 TI - High resistance of Isaria fumosorosea to carbendazim arises from the overexpression of an ATP-binding cassette transporter (ifT1) rather than tubulin mutation. AB - AIMS: Probing possible mechanisms involved in the resistance of entomopathogenic fungus Isaria fumosorosea to carbendazim fungicide. METHODS AND RESULTS: A carbendazim-sensitive strain (If116) selected from 15 wild-type strains was subjected to NaNO(2) -induced mutagenesis, yielding nine mutants with carbendazim resistance increased by 82- to 830-fold and thermotolerance decreased by 15-51%. Comparing the protein sequences deduced from the alpha- and beta-tubulin genes of If116 and its mutants revealed no traceable site mutation relating to the enhanced resistance although the transcripts levels of beta-tubulin gene in all mutants were 0.87- to 7.16-fold of that in If116. Three examined mutants showed multidrug resistance because they were significantly more resistant to glufosinate, imidacloprid and other six fungicides than If116 during growth. Further examination of rhodamine-stained blastospores revealed existence of drug efflux pump protein(s) in all carbendazim-resistant mutants. Thus, the sequences of an ATP-binding cassette (ABC) transporter gene (ifT1) and its promoter region cloned from the wild-type and mutant strains were analysed. Three common point mutations were located, respectively, at the binding sites of Gal4, Abf1 and Raf, which are crucial transcription factors in the regulative network of numerous protein loci. Such point mutations elevated the ifT1 expression by 17 to 137-fold in all the mutants. CONCLUSIONS: The overexpression of the ABC transporter caused by the point mutations at the binding sites was responsible for the fungal resistance to various pesticides including carbendazim. SIGNIFICANCE AND IMPACT OF STUDY: The transporter-mediated multidrug resistance found for the first time in entomopathogenic fungi is potential for use in improving mycoinsecticide compatibility with chemical pesticides. PMID- 22044667 TI - Association between olfactory receptor genes, eating behavior traits and adiposity: results from the Quebec Family Study. AB - Obesity is a major health problem that can be influenced by eating behaviors. Evidence suggests that the sensory properties of food influence eating behaviors and lead to overeating and overweight. A previous genome-wide linkage scan for eating behavior traits assessed with the Three-Factor Eating Questionnaire (cognitive dietary restraint, disinhibition and hunger) performed in the Quebec Family Study (QFS) revealed a quantitative trait locus for disinhibition on chromosome 19p13. This region encodes a cluster of seven olfactory receptor (OR) genes, including OR7D4, previously associated with odor perceptions. Direct sequencing of the OR7D4 gene revealed 16 sequence variants. Nine OR7D4 sequence variants with minor allele frequency (MAF)>1% as well as 100 SNPs spanning the cluster of OR genes on 19p13 were tested for association with age- and sex adjusted eating behaviors as well as adiposity traits in 890 subjects. One OR7D4 sequence variant (rs2878329 G>A) showed evidence of association with reduced levels of adiposity (p=0.03), cognitive dietary restraint (p=0.05) and susceptibility to hunger (p=0.008). None of the OR7D4 SNPs was associated with disinhibition, but a SNP (rs2240927) in another OR gene (OR7E24) showed evidence of association (p=0.03). Another SNP in the OR7G3 gene (rs10414255) was also found to be associated with adiposity and eating behaviors. These results are the first to suggest that variations in human olfactory receptor genes can influence eating behaviors and adiposity. The associations reported in the present study should be interpreted with caution considering the number of tests performed and considered as potential new hypotheses about the effects OR polymorphisms on eating behaviors and obesity that need to be further explored in other populations. PMID- 22044668 TI - Inverse correlation of free and immune complex-sequestered anti-ADAMTS13 antibodies in a patient with acquired thrombotic thrombocytopenic purpura. PMID- 22044669 TI - The phosphatase PHLPP1 regulates Akt2, promotes pancreatic cancer cell death, and inhibits tumor formation. AB - BACKGROUND & AIMS: The kinase Akt mediates resistance of pancreatic cancer (PaCa) cells to death and is constitutively active (phosphorylated) in cancer cells. Whereas the kinases that activate Akt are well characterized, less is known about phosphatases that dephosporylate and thereby inactivate it. We investigated regulation of Akt activity and cell death by the phosphatases PHLPP1 and PHLPP2 in PaCa cells, mouse models of PaCa, and human pancreatic ductal adenocarcinoma (PDAC). METHODS: We measured the effects of PHLPP overexpression or knockdown with small interfering RNAs on Akt activation and cell death. We examined regulation of PHLPPs by growth factors and reactive oxygen species, as well as associations between PHLPPs and tumorigenesis. RESULTS: PHLPP overexpression inactivated Akt, whereas PHLPP knockdown increased phosphorylation of Akt in PaCa cells. Levels of PHLPPs were greatly reduced in human PDAC and in mouse genetic and xenograft models of PaCa. PHLPP activities in PaCa cells were down-regulated by growth factors and Nox4 reduced nicotinamide adenine dinucleotide phosphate oxidase. PHLPP1 selectively dephosphorylated Akt2, whereas PHLPP2 selectively dephosphorylated Akt1. Akt2, but not Akt1, was up-regulated in PDAC, and Akt2 levels correlated with mortality. Consistent with these results, high levels of PHLPP1, which dephosphorylates Akt2 (but not PHLPP2, which dephosphorylates Akt1), correlated with longer survival times of patients with PDAC. In mice, xenograft tumors derived from PaCa cells that overexpress PHLPP1 (but not PHLPP2) had inactivated Akt, greater extent of apoptosis, and smaller size. CONCLUSIONS: PHLPP1 has tumor suppressive activity and might represent a therapeutic or diagnostic tool for PDAC. PMID- 22044671 TI - A single administration of the GnRH antagonist acyline inhibits basal and GnRH stimulated serum testosterone concentrations in male dogs. AB - The objective of this study was to describe testosterone (T) response to GnRH challenge in antagonist-treated dogs over a 30-day period. Eight mongrel dogs were randomly assigned to either the GnRH antagonist acyline 330 MUg/kg sc (ACY; n = 4) or a placebo group (PLA; n = 4). The dogs were serially challenged with the GnRH agonist, buserelin 0.2 MUg/kg sc on days -1, 1, 3, 7, 10, 14, 21 and 30. On these days, blood samples for T determinations were collected before (-30 min) and 60, 120 and 180 min after the agonist injection. Basal (-30 min) and post GnRH agonist stimulation T values were compared by anova for repeated measures. Before treatments (day -1), there were no differences in basal T serum concentrations between groups (p > 0.1). After treatments, basal T showed a significant interaction between treatment and day (p < 0.05). Furthermore, when both groups were analysed independently, basal T varied in the ACY (p < 0.01) but not in the PLA group (p > 0.1). On day -1, before treatments, the stimulation tests had only a time effect (p = 0.05) although on days 1 (p < 0.01), 3 (p < 0.01), 7 (p < 0.01), 10 (p < 0.01) and 14 (p < 0.05), the response to the agonist differed between groups, becoming similar on days 21 (p > 0.05) and 30 (p > 0.05). It was concluded that, in dogs, a single administration of the GnRH antagonist prevented canine gonadal axis to physiologically respond to agonistic challenge during 14 days. PMID- 22044670 TI - Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice. AB - BACKGROUND & AIMS: Integrity of the intestinal epithelium is required for nutrition absorption and defense against pathogens. Claudins are cell adhesion molecules that localize at tight junctions (TJs); many are expressed in the intestinal tract, but little is known about their functions. Claudin-7 is unique in that it has a stronger basolateral membrane distribution than other claudins, which localize primarily to apical TJs in the intestinal epithelium. We investigated the basolateral functions of claudin-7 and assessed the effects of disruption of Cldn7 in intestines of mice. METHODS: We generated Cldn7(-/-) mice and examined their intestines by histology, molecular and cellular biology, and biochemistry approaches. We performed gene silencing experiments in epithelial cell lines using small interfering RNAs (siRNAs). RESULTS: The Cldn7(-/-) mice had severe intestinal defects that included mucosal ulcerations, epithelial cell sloughing, and inflammation. Intestines of Cldn7(-/-) mice produced significantly higher levels of cytokines, the nuclear factor kappaB p65 subunit, and cyclooxygenase 2; they also up-regulated expression of matrix metalloproteinases (MMPs)-3 and -7. siRNA in epithelial cell lines showed that the increased expression of MMP-3 resulted directly from claudin-7 depletion, whereas that of MMP-7 resulted from inflammation. Electron microscopy analysis showed that intestines of Cldn7(-/-) mice had intercellular gaps below TJs and cell matrix loosening. Deletion of Cldn7 reduced expression and altered localization of the integrin alpha2 subunit in addition to disrupting formation of complexes of claudin-7, integrin alpha2, and claudin-1 that normally form in epithelial basolateral compartments of intestines. CONCLUSIONS: In mice, claudin-7 has non TJ functions, including maintenance of epithelial cell-matrix interactions and intestinal homeostasis. PMID- 22044672 TI - Effects of acute and chronic treatment elicited by lamotrigine on behavior, energy metabolism, neurotrophins and signaling cascades in rats. AB - The present study was aimed to investigate the behavioral and molecular effects of lamotrigine. To this aim, Wistar rats were treated with lamotrigine (10 and 20 mg/kg) or imipramine (30 mg/kg) acutely and chronically. The behavior was assessed using forced swimming test. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), Proteina Kinase B (PKB, AKT), glycogen synthase kinase 3 (GSK-3) and B-cell lymphoma 2 (Bcl-2) levels, citrate synthase, creatine kinase and mitochondrial chain (I, II, II-III and IV) activities were assessed in the brain. The results showed that both treatments reduced the immobility time. The BDNF were increased in the prefrontal after acute treatment with lamotrigine (20 mg/kg), and the BDNF and NGF were increased in the prefrontal after chronic treatment with lamotrigine in all doses. The AKT increased and Bcl-2 and GSK-3 decreased after both treatments in all brain areas. The citrate synthase and creatine kinase increased in the amygdala after acute treatment with imipramine. Chronic treatment with imipramine and lamotrigine (10 mg/kg) increased the creatine kinase in the hippocampus. The complex I was reduced and the complex II, II-III and IV were increased, but related with treatment and brain area. In conclusion, lamotrigine exerted antidepressant-like, which can be attributed to its effects on pathways related to depression, such as neurotrophins, metabolism energy and signaling cascade. PMID- 22044673 TI - Pulmonary function and left ventricular mass in African Americans: the Atherosclerosis Risk in Communities (ARIC) study. AB - PURPOSE: Impaired pulmonary function has been associated with increased cardiovascular disease incidence and mortality. The objective of this study was to investigate associations between pulmonary function and left ventricular (LV) mass. METHODS: Participants were African American women (n = 1,069) and men (n = 555) aged 49-73 years, from the Atherosclerosis Risk in Communities study. Mean pulmonary function values at the first (1987-1989) and second (1990-1992) examinations were used. Echocardiograms were performed at the third and early in the fourth examinations (1993-1996). Analysis of covariance and linear regression were used to assess associations. RESULTS: Mean levels of LV mass decreased with increasing quintiles of forced expiratory volume in one second (FEV(1) ) among female never smokers (P = 0.039). Forced vital capacity (FVC) showed stronger associations than FEV(1) with LV mass. Among men, LV mass was positively associated with FEV(1) among current and never smokers, and with FVC among never smokers. Additional analyses among never smokers revealed significant inverse associations between LV mass and FVC among women with waist-to-hip ratios of >0.85 and those with no history of diabetes. In contrast, significant positive associations between LV mass and FVC were seen among male never smokers with body mass index (BMI) of <=24.9 kg/m(2) , waist-to-hip ratios of <=0.95, no history of hypertension or diabetes, and <=60 years old. BMI and waist-to-hip ratio significantly modified associations among men. CONCLUSIONS: Among never smokers, LV mass and pulmonary function were inversely associated among women and positively associated among men. Further studies are warranted. PMID- 22044674 TI - Antibiosis of vineyard ecosystem fungi against food-borne microorganisms. AB - Fermentation extracts from fungi isolated from vineyard ecosystems were tested for antimicrobial activities against a set of test microorganisms, including five food-borne pathogens (Staphylococcus aureus EP167, Acinetobacter baumannii (clinically isolated), Pseudomonas aeruginosa PAO1, Escherichia coli O157:H7 (CECT 5947) and Candida albicans MY1055) and two probiotic bacteria (Lactobacillus plantarum LCH17 and Lactobacillus brevis LCH23). A total of 182 fungi was grown in eight different media, and the fermentation extracts were screened for antimicrobial activity. A total of 71 fungi produced extracts active against at least one pathogenic microorganism, but not against any probiotic bacteria. The Gram-positive bacterium S. aureus EP167 was more susceptible to antimicrobial fungi broth extracts than Gram-negative bacteria and pathogenic fungi. Identification of active fungi based on internal transcribed spacer rRNA sequence analysis revealed that species in the orders Pleosporales, Hypocreales and Xylariales dominated. Differences in antimicrobial selectivity were observed among isolates from the same species. Some compounds present in the active extracts were tentatively identified by liquid chromatography-mass spectrometry. Antimicrobial metabolites produced by vineyard ecosystem fungi may potentially limit colonization and spoilage of food products by food-borne pathogens, with minimal effect on probiotic bacteria. PMID- 22044675 TI - Takotsubo cardiomyopathy has a unique cardiac biomarker profile: NT proBNP/myoglobin and NT-proBNP/troponin T ratios for the differential diagnosis of acute coronary syndromes and stress induced cardiomyopathy. AB - BACKGROUND: Takotsubo cardiomyopathy (TC) usually is not recognized until heart catheterization reveals typical wall motion abnormalities in the absence of significant coronary artery disease. It was our aim to identify TC by its unique cardiac biomarker profile at an early stage and, preferably, with non-invasive procedures only. METHODS: Ratios of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and myoglobin, NT-proBNP and troponin T (TnT), NT-proBNP and creatinekinase-MB (CK-MB) were compared in patients with TC (n=39), patients with ST-elevation myocardial infarction (STEMI, n=48) and patients with non-ST elevation myocardial infarction (NSTEMI, n=34). Biomarkers were recorded serially at admission and at the three consecutive days. Optimal cut-off values to distinguish TC from STEMI and NSTEMI were calculated with receiver operator characteristic (ROC) curves. RESULTS: At admission a NT-proBNP (ng/l)/myoglobin (MUg/l) ratio of 3.8, distinguished TC from STEMI (sensitivity: 89%, specificity: 90%), while a NT-proBNP (ng/l)/myoglobin (MUg/l) ratio of 14 separated well between TC and NSTEMI (sensitivity: 65%, specificity: 90%). Best differentiation of TC and ACS was possible with the ratio of peak levels of NT-proBNP (ng/l)/TnT (MUg/l). A cut-off value of NT-proBNP (ng/l)/TnT (MUg/l) ratio of 2889, distinguished TC from STEMI (sensitivity: 91%, specificity: 95%), while a NT proBNP (ng/l)/TnT (MUg/l) ratio of 5000 separated well between TC and NSTEMI (sensitivity: 83%, specificity: 95%). CONCLUSIONS: TC goes along with a singular cardiac biomarker profile, which might be useful to identify patients with TC among patients presenting with acute coronary syndromes (ACS). PMID- 22044676 TI - In vivo and in silico determination of essential genes of Campylobacter jejuni. AB - BACKGROUND: In the United Kingdom, the thermophilic Campylobacter species C. jejuni and C. coli are the most frequent causes of food-borne gastroenteritis in humans. While campylobacteriosis is usually a relatively mild infection, it has a significant public health and economic impact, and possible complications include reactive arthritis and the autoimmune diseases Guillain-Barre syndrome. The rapid developments in "omics" technologies have resulted in the availability of diverse datasets allowing predictions of metabolism and physiology of pathogenic micro organisms. When combined, these datasets may allow for the identification of potential weaknesses that can be used for development of new antimicrobials to reduce or eliminate C. jejuni and C. coli from the food chain. RESULTS: A metabolic model of C. jejuni was constructed using the annotation of the NCTC 11168 genome sequence, a published model of the related bacterium Helicobacter pylori, and extensive literature mining. Using this model, we have used in silico Flux Balance Analysis (FBA) to determine key metabolic routes that are essential for generating energy and biomass, thus creating a list of genes potentially essential for growth under laboratory conditions. To complement this in silico approach, candidate essential genes have been determined using a whole genome transposon mutagenesis method. FBA and transposon mutagenesis (both this study and a published study) predict a similar number of essential genes (around 200). The analysis of the intersection between the three approaches highlights the shikimate pathway where genes are predicted to be essential by one or more method, and tend to be network hubs, based on a previously published Campylobacter protein-protein interaction network, and could therefore be targets for novel antimicrobial therapy. CONCLUSIONS: We have constructed the first curated metabolic model for the food-borne pathogen Campylobacter jejuni and have presented the resulting metabolic insights. We have shown that the combination of in silico and in vivo approaches could point to non-redundant, indispensable genes associated with the well characterised shikimate pathway, and also genes of unknown function specific to C. jejuni, which are all potential novel Campylobacter intervention targets. PMID- 22044677 TI - Light and portable novel device for diabetic retinopathy screening. AB - BACKGROUND: To validate the use of an economical portable multipurpose ophthalmic imaging device, EyeScan (Ophthalmic Imaging System, Sacramento, CA, USA), for diabetic retinopathy screening. DESIGN: Evaluation of a diagnostic device. PARTICIPANTS: One hundred thirty-six (272 eyes) were recruited from diabetic retinopathy screening clinic of Royal Perth Hospital, Western Australia, Australia. METHODS: All patients underwent three-field (optic disc, macular and temporal view) mydriatic retinal digital still photography captured by EyeScan and FF450 plus (Carl Zeiss Meditec, North America) and were subsequently examined by a senior consultant ophthalmologist using the slit-lamp biomicroscopy (reference standard). All retinal images were interpreted by a consultant ophthalmologist and a medical officer. MAIN OUTCOME MEASURES: The sensitivity, specificity and kappa statistics of EyeScan and FF450 plus with reference to the slit-lamp examination findings by a senior consultant ophthalmologist. RESULTS: For detection of any grade of diabetic retinopathy, EyeScan had a sensitivity and specificity of 93 and 98%, respectively (ophthalmologist), and 92 and 95%, respectively (medical officer). In contrast, FF450 plus images had a sensitivity and specificity of 95 and 99%, respectively (ophthalmologist), and 92 and 96%, respectively (medical officer). The overall kappa statistics for diabetic retinopathy grading for EyeScan and FF450 plus were 0.93 and 0.95 for ophthalmologist and 0.88 and 0.90 for medical officer, respectively. CONCLUSIONS: Given that the EyeScan requires minimal training to use and has excellent diagnostic accuracy in screening for diabetic retinopathy, it could be potentially utilized by the primary eye care providers to widely screen for diabetic retinopathy in the community. PMID- 22044678 TI - Land trust evaluation of progress toward conservation goals. AB - In the United States local land trusts preserve and conserve land to protect water quality and supply, farmlands, habitat for native plants and animals, areas of cultural or historical significance, and scenic views. We surveyed the 24 active, local land trusts in North Carolina (U.S.A.) to determine how they report progress toward attaining such conservation goals. Twenty-two land trusts responded to our survey. Of these, eight reported developing specific conservation goals for all of the properties they protect, five identified conservation targets on all properties, and two reported monitoring biological indicators on all of their protected properties. On the basis of these results, we believe most of the land trusts surveyed could not determine whether they were meeting conservation goals because most did not identify explicit, measurable goals and monitor progress toward them. Instead they reported success in terms of the amount of land protected and money raised. We think this is a lost opportunity for land trusts to build sound approaches to environmental management, engage the public, entice new donors, and attain funding for additional conservation activities. We propose conservation professionals help local land trusts adopt the Open Standards for the Practice of Conservation, a framework developed by a consortium of international conservation organizations, to develop conservation goals and measure whether the goals are achieved. PMID- 22044679 TI - Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori. AB - Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin beta1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed. PMID- 22044680 TI - Fighting resistant tuberculosis with old compounds: the carbapenem paradigm. PMID- 22044681 TI - Service providers' perceptions of active ageing among older adults with lifelong intellectual disabilities. AB - BACKGROUND: Considerable attention is currently being directed towards both active ageing and the revising of standards for disability services within Australia and internationally. Yet, to date, no consideration appears to have been given to ways to promote active ageing among older adults with intellectual disabilities (IDs). METHODS: Semi-structured interviews were conducted with 16 Australian professional direct-care support staff (service providers) about their perceptions of ageing among older adults with lifelong IDs and what active ageing might entail for an individual from this population who is currently under their care, in both the present and future. Data were analysed against the six core World Health Organization active ageing outcomes for people with IDs. RESULTS: Service providers appeared to be strongly focused on encouraging active ageing among their clients. However, their perceptions of the individual characteristics, circumstances and experiences of older adults with IDs for whom they care suggest that active ageing principles need to be applied to this group in a way that considers both their individual and diverse needs, particularly with respect to them transitioning from day services, employment or voluntary work to reduced activity, and finally to aged care facilities. The appropriateness of this group being placed in nursing homes in old age was also questioned. CONCLUSION: Direct-care staff of older adults with IDs have a vital role to play in encouraging and facilitating active ageing, as well as informing strategies that need to be implemented to ensure appropriate care for this diverse group as they proceed to old age. PMID- 22044682 TI - Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjogren's syndrome. AB - INTRODUCTION: In Sjogren's syndrome, keratoconjunctivitis sicca (dry eye) is associated with infiltration of lacrimal glands by leukocytes and consequent losses of tear-fluid production and the integrity of the ocular surface. We investigated the effect of blockade of the lymphotoxin-beta receptor (LTBR) pathway on lacrimal-gland pathology in the NOD mouse model of Sjogren's syndrome. METHODS: Male NOD mice were treated for up to ten weeks with an antagonist, LTBR Ig, or control mouse antibody MOPC-21. Extra-orbital lacrimal glands were analyzed by immunohistochemistry for high endothelial venules (HEV), by Affymetrix gene-array analysis and real-time PCR for differential gene expression, and by ELISA for CXCL13 protein. Leukocytes from lacrimal glands were analyzed by flow-cytometry. Tear-fluid secretion-rates were measured and the integrity of the ocular surface was scored using slit-lamp microscopy and fluorescein isothiocyanate (FITC) staining. The chemokine CXCL13 was measured by ELISA in sera from Sjogren's syndrome patients (n = 27) and healthy controls (n = 30). Statistical analysis was by the two-tailed, unpaired T-test, or the Mann Whitney-test for ocular integrity scores. RESULTS: LTBR blockade for eight weeks reduced B-cell accumulation (approximately 5-fold), eliminated HEV in lacrimal glands, and reduced the entry rate of lymphocytes into lacrimal glands. Affymetrix-chip analysis revealed numerous changes in mRNA expression due to LTBR blockade, including reduction of homeostatic chemokine expression. The reduction of CXCL13, CCL21, CCL19 mRNA and the HEV-associated gene GLYCAM-1 was confirmed by PCR analysis. CXCL13 protein increased with disease progression in lacrimal gland homogenates, but after LTBR blockade for 8 weeks, CXCL13 was reduced approximately 6-fold to 8.4 pg/mg (+/- 2.7) from 51 pg/mg (+/-5.3) in lacrimal glands of 16 week old control mice. Mice given LTBR blockade exhibited an approximately two-fold greater tear-fluid secretion than control mice (P = 0.001), and had a significantly improved ocular surface integrity score (P = 0.005). The mean CXCL13 concentration in sera from Sjogren's patients (n = 27) was 170 pg/ml, compared to 92.0 pg/ml for sera from (n = 30) healthy controls (P = 0.01). CONCLUSIONS: Blockade of LTBR pathways may have therapeutic potential for treatment of Sjogren's syndrome. PMID- 22044683 TI - Age, gender, will, and use of home-visit nursing care are critical factors in home care for malignant diseases; a retrospective study involving 346 patients in Japan. AB - BACKGROUND: We aimed to clarify the factors affecting outcomes of home care for patients with malignant diseases. METHODS: Of 607 patients who were treated in 10 clinics specialized in home care between January and December 2007 at Chiba, Fukuoka, Iwate, Kagoshima, Tochigi and Tokyo prefectures across Japan, 346 (57%; 145 men and 201 women) had malignant diseases. We collected information on medical and social backgrounds, details of home care, and its outcomes based on their medical records. RESULTS: Median age of the patients was 77 years (range, 11-102), and 335 patients were economically self-sufficient. Their general condition was poor; advanced cancer (n = 308), performance status of 3-4 (n = 261), and dementia (n = 121). At the beginning of home care, 143 patients and 174 family members expressed their wish to die at home. All the patients received supportive treatments including fluid replacement and oxygenation. Median duration of home care was 47 days (range, 0-2,712). 224 patients died at home. For the remaining 122, home care was terminated due to complications (n = 109), change of attending physicians (n = 8), and others (n = 5). The factors which inhibited the continuity of home care were the non-use of home-visit nursing care (hazard ratio [HR] = 1.78, 95% confidence interval [CI]: 1.05-3.00, p = 0.03), the fact that the patients themselves do not wish to die at home (HR = 1.83, CI: 1.09-3.07, p = 0.02), women (HR = 1.81, CI: 1.11-2.94, p = 0.02), and age (HR = 0.98, CI: 0.97-1.00, p = 0.02). CONCLUSIONS: Continuation of home care is influenced by patients' age, gender, will, and use of home-visit nursing. PMID- 22044685 TI - Hydrolysis optimization and characterization study of preparing fatty acids from Jatropha curcas seed oil. AB - BACKGROUND: Fatty acids (FAs) are important as raw materials for the biotechnology industry. Existing methods of FAs production are based on chemical methods. In this study potassium hydroxide (KOH)-catalyzed reactions were utilized to hydrolysis Jatropha curcas seed oil. RESULTS: The parameters effect of ethanolic KOH concentration, reaction temperature, and reaction time to free fatty acid (FFA%) were investigated using D-Optimal Design. Characterization of the product has been studied using Fourier transforms infrared spectroscopy (FTIR), gas chromatography (GC) and high performance liquid chromatography (HPLC). The optimum conditions for maximum FFA% were achieved at 1.75M of ethanolic KOH concentration, 65 degrees C of reaction temperature and 2.0 h of reaction time. CONCLUSIONS: This study showed that ethanolic KOH concentration was significant variable for J. curcas seed oil hydrolysis. In a 18-point experimental design, FFA% of hydrolyzed J. curcas seed oil can be raised from 1.89% to 102.2%, which proved by FTIR and HPLC. PMID- 22044686 TI - Extensive recombination events and horizontal gene transfer shaped the Legionella pneumophila genomes. AB - BACKGROUND: Legionella pneumophila is an intracellular pathogen of environmental protozoa. When humans inhale contaminated aerosols this bacterium may cause a severe pneumonia called Legionnaires' disease. Despite the abundance of dozens of Legionella species in aquatic reservoirs, the vast majority of human disease is caused by a single serogroup (Sg) of a single species, namely L. pneumophila Sg1. To get further insights into genome dynamics and evolution of Sg1 strains, we sequenced strains Lorraine and HL 0604 1035 (Sg1) and compared them to the available sequences of Sg1 strains Paris, Lens, Corby and Philadelphia, resulting in a comprehensive multigenome analysis. RESULTS: We show that L. pneumophila Sg1 has a highly conserved and syntenic core genome that comprises the many eukaryotic like proteins and a conserved repertoire of over 200 Dot/Icm type IV secreted substrates. However, recombination events and horizontal gene transfer are frequent. In particular the analyses of the distribution of nucleotide polymorphisms suggests that large chromosomal fragments of over 200 kbs are exchanged between L. pneumophila strains and contribute to the genome dynamics in the natural population. The many secretion systems present might be implicated in exchange of these fragments by conjugal transfer. Plasmids also play a role in genome diversification and are exchanged among strains and circulate between different Legionella species. CONCLUSION: Horizontal gene transfer among bacteria and from eukaryotes to L. pneumophila as well as recombination between strains allows different clones to evolve into predominant disease clones and others to replace them subsequently within relatively short periods of time. PMID- 22044687 TI - Decreased xanthine oxidoreductase (XOR) is associated with a worse prognosis in patients with serous ovarian carcinoma. AB - OBJECTIVE: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high-energy phosphates. In the human cancers previously studied, down-regulated XOR identifies patients with unfavorable prognosis. We assessed the clinical relevance of XOR expression in serous ovarian cancer. METHODS: XOR protein was determined in tissue microarrays from 474 patients with serous ovarian cancer and analyzed with respect to clinical parameters and survival. RESULTS: XOR was down regulated in 64% of the tumors as compared to the corresponding normal tissue. Decreased XOR was associated with a poorly differentiated tumor and an abnormal p53 expression, but not with age at diagnosis, FIGO stage, Ki-67 or tumor size. XOR expression was associated with outcome, and the five year ovarian cancer specific survival in patients with strong XOR expression was 59% compared to 44% in those with moderate (hazard ratio, HR; 1.44; P=0.0083) and 26% in patients with lack of XOR (HR, 2.07; P=0.0003). This was also true in patients whose tumors were highly differentiated (HR, 3.67; P=0.008) and in patients with a small (<1cm) residual tumor (HR, 2.62; P=0.017), and in patients whose tumors show a low Ki-67 protein expression (HR, 3.79; P<0.0001). In multivariate survival analysis, absence of XOR emerged as an independent prognostic factor (HR, 1.82; P=0.015). CONCLUSIONS: Decreased XOR is associated with poorer prognosis in patients with serous ovarian cancer especially in those with an otherwise more favorable prognostic profile. PMID- 22044688 TI - Involvement in decision-making about treatment and ovarian cancer survivor quality of life. AB - PURPOSE: This study sought to better understand the long-term effects on women's health related quality of life (HRQOL) of involvement in decision-making about their surgical and chemotherapeutic treatments for ovarian cancer treatment and about follow-up care after treatment. METHODS: Using a cross-sectional survey design, a sample of 219 ovarian cancer patient/survivors from Western Washington who were between 3 months and ten years post-diagnosis were recruited via a mailed survey sent by their gynecological oncologist and interviewed about their ovarian cancer treatment, use of Complementary and Alternative Medicine (CAM), Health related quality of life, and their involvement in decision-making about their cancer treatment and follow-up care. RESULTS: Multivariate regression analyses revealed age, but not stage of cancer to be a significant predictor of perceived involvement in decision-making about ovarian cancer treatment and follow-up. Age also predicted CAM use with older patients using herbal CAM, and younger patients using CAM activities and CAM providers (p<0.5). Controlling for demographic, disease, and treatment characteristics involvement in decision making about surgery and follow-up care were associated with better mental health in survivorship (p<0.05). Involvement in decision-making about use of CAM and about lifestyle health changes was associated with greater vitality and better role-emotional health in survivorship (respectively; both; p<0.05). CONCLUSIONS: As has been found in studies of breast cancer survivors, perceived involvement in decision-making about ovarian cancer treatment including surgery and follow-up care after treatment is associated with better quality of life for cancer survivors. Involvement in decision-making about the use of CAM and about changes in lifestyle health practices also appear to help survivor's emotional health related quality of life. Prospective studies are needed to determine the mechanisms by which perceived involvement in decision-making about treatment might influence survivor quality of life. PMID- 22044689 TI - BRCA1 and BRCA2 mutations among ovarian cancer patients from Colombia. AB - OBJECTIVE: The contribution of BRCA1 and BRCA2 mutations to ovarian cancer in Colombia has not yet been explored. Five founder mutations have been identified in two previous studies of breast cancer patients in the Bogota region [1,2]. It is important that the frequency of mutations be established among unselected cases of ovarian cancer in order to estimate the genetic burden of this cancer in Colombia and to plan genetic and preventive services. METHODS: We enrolled 100 unselected women with ovarian cancer from the Bogota region, and from northern and southern central regions of Colombia. A detailed family history was obtained from each patient and a blood sample was processed for DNA analysis. DNA quality was adequate for BRCA testing for 96 women. Mutations in BRCA1 and BRCA2 were sought using a Hispanic BRCA mutation testing panel. All mutations were confirmed by direct sequencing. RESULTS: Fifteen mutations were identified (two in BRCA2 and thirteen in BRCA1) representing 15.6% of the total (95% CI: 7.8% to 21.3%). Among the 15 mutation-positive families there were nine breast-ovarian cancer families, one gastric cancer family, one prostate cancer family, three uterine cancer families, and one family with no history of cancer. A single founder mutation in BRCA1 (3450del4) was seen in 11 patients. CONCLUSION: In summary, BRCA1 founder mutations are common in Colombian women with ovarian cancer. Approximately 11.5% of all ovarian cancer cases in the Bogota region are attributable to a single BRCA1 founder mutation. PMID- 22044690 TI - Characterization of hTERT-immortalized caprine mammary epithelial cells. AB - The aim of this article is to demonstrate and characterize caprine mammary epithelial cells (CMC) immortalized with human telomerase reverse transcriptase (hTERT) gene. Five immortalized CMCs were assigned to either myoepithelial or luminal epithelial groups based on their morphology and expression of cell lineage-specific intermediate filaments. Telomeric repeat amplification protocol revealed various telomerase activities in CMCs associated with their distinct proliferation potential. Karyotypic analysis showed three CMCs retained their modal Capra hircus chromosome number (2n = 60), whereas the remaining two CMCs were abnormal at 2n = 19 and 2n = 36. CMCs with abnormal karyotypes lost p53 protein after chemical-induced DNA damage and showed anchorage-independent growth in soft agar assay. In terms of functional differentiation, luminal CMCs organized into alveolus-like structures when grown in Matrigel. Furthermore, alphas1- and beta-casein gene was induced in luminal CMCs in response to lacto hormones stimulation. Together these results showed that hTERT-immortalized CMCs retained major characteristics of mammary epithelial cells, and stability of the genome is required for maintaining normal mammary epithelium function. Application of CMCs can provide valuable models to study alveologenesis and lactogenesis of mammary epithelium and test the feasibility of recombinant constructs designed for the generation of transgenic livestock. PMID- 22044692 TI - Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII in experimental haemophilia A. AB - The development of inhibitory anti-factor VIII (FVIII) antibodies in patients with haemophilia A following replacement therapy is associated with several types of risk factors. Among these, the purity of FVIII concentrates, and in particular the presence of von Willebrand factor (VWF), was controversially proposed to influence the immunogenicity of exogenous FVIII. We re-assessed in vivo and in vitro the immuno-protective effect of VWF towards FVIII. The immuno-protective effect of VWF towards FVIII was investigated in vivo, in a model of haemophilia A. We studied the endocytosis of FVIII by murine bone marrow-derived dendritic cells and evaluated the capacity of VWF to block the internalization of FVIII. We characterized the relevance of VWF for the accumulation of FVIII in the marginal zone of the spleen, a secondary lymphoid organ where the immune response to therapeutically administered FVIII initiates. Our results confirm that VWF reduces the immunogenicity of FVIII in FVIII-deficient mice. Paradoxically, VWF is important for the accumulation of FVIII in the marginal zone of the spleen. We propose that VWF exerts at least two non-mutually exclusive immunoprotective roles towards FVIII in haemophilic mice: VWF prevents the endocytosis of FVIII by professional antigen-presenting cells by blocking the interaction of FVIII with as yet unidentified endocytic receptor(s). Hypothetically, VWF, by virtue of increasing the half-life of FVIII in the circulation, may allow an increased contact time with tolerogenic marginal zone B cells in the spleen. PMID- 22044691 TI - Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the FNCLCC-PACS 01 randomized trial. AB - INTRODUCTION: The PACS01 trial has demonstrated that a docetaxel addition to adjuvant anthracycline-based chemotherapy improves disease-free survival (DFS) and overall survival of node-positive early breast cancer (EBC). We searched for prognostic and predictive markers for docetaxel's benefit. METHODS: Tumor samples from 1,099 recruited women were analyzed for the expression of 34 selected proteins using immunohistochemistry. The prognostic and predictive values of each marker and four molecular subtypes (luminal A, luminal B, HER2-overexpressing, and triple-negative) were tested. RESULTS: Progesterone receptor-negativity (HR = 0.66; 95% CI 0.47 to 0.92, P = 0.013), and Ki67-positivity (HR = 1.53; 95% CI 1.12 to 2.08, P = 0.007) were independent adverse prognostic factors. Out of the 34 proteins, only Ki67-positivity was associated with DFS improvement with docetaxel addition (adjusted HR = 0.51, 95% CI 0.33 to 0.79 for Ki67-positive versus HR = 1.10, 95% CI 0.75 to 1.61 for Ki67-negative tumors, P for interaction = 0.012). Molecular subtyping predicted the docetaxel benefit, but without providing additional information to Ki67 status. The luminal A subtype did not benefit from docetaxel (HR = 1.16, 95% CI 0.73 to 1.84); the reduction in the relapse risk was 53% (HR = 0.47, 95% CI 0.22 to 1.01), 34% (HR = 0.66, 95% CI 0.37 to 1.19), and 12% (HR = 0.88, 95% CI 0.49 to 1.57) in the luminal B, HER2 overexpressing, and triple-negative subtypes, respectively. CONCLUSIONS: In patients with node-positive EBC receiving adjuvant anthracycline-based chemotherapy, the most powerful predictor of docetaxel benefit is Ki67 positivity. PMID- 22044693 TI - Hepatic transplant and HCV: a new playground for an old virus. AB - Hepatitis C virus (HCV) infection is a major global health problem affecting 170 million people worldwide. The majority of infected individuals fail to resolve their infection, with a significant number developing chronic, progressive HCV related liver disease. HCV infection is the leading indication for liver transplantation and unfortunately, all patients with detectable viral load before transplantation will have rapid, recurrent infection. What remain to be determined are factors contributing to the severity of HCV recurrence. Such factors are unique to the posttransplant setting and include: viral genetic diversity and composition, immunosuppression, donor/recipient age and sex, genetic factors and the liver microenvironment. Importantly, the possibility that the severity of HCV recurrence might be also influenced by factors related to the primary course of disease (i.e. viral set point, previously acquired adaptations of the virus) must be further evaluated. In this sense, recurrent HCV infection should not be regarded merely as another acute infection, but rather, it should be cautioned that problems first arising during the primary course of disease may be accentuated during recurrence. Development of novel therapeutic approaches will require a thorough understanding of viral and host determinants of infection resolution and how these factors may change in the posttransplant setting. PMID- 22044694 TI - Randomized, double-blind, placebo-controlled trial of polyphenon E in prostate cancer patients before prostatectomy: evaluation of potential chemopreventive activities. AB - Compelling preclinical and pilot clinical data support the role of green tea polyphenols in prostate cancer prevention. We conducted a randomized, double blind, placebo-controlled trial of polyphenon E (enriched green tea polyphenol extract) in men with prostate cancer scheduled to undergo radical prostatectomy. The study aimed to determine the bioavailability of green tea polyphenols in prostate tissue and to measure its effects on systemic and tissue biomarkers of prostate cancer carcinogenesis. Participants received either polyphenon E (containing 800 mg epigallocatechin gallate) or placebo daily for 3 to 6 weeks before surgery. Following the intervention, green tea polyphenol levels in the prostatectomy tissue were low to undetectable. Polyphenon E intervention resulted in favorable but not statistically significant changes in serum prostate-specific antigen, serum insulin-like growth factor axis, and oxidative DNA damage in blood leukocytes. Tissue biomarkers of cell proliferation, apoptosis, and angiogenesis in the prostatectomy tissue did not differ between the treatment arms. The proportion of subjects who had a decrease in Gleason score between biopsy and surgical specimens was greater in those on polyphenon E but was not statistically significant. The study's findings of low bioavailability and/or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers from 3 to 6 weeks of administration suggests that prostate cancer preventive activity of green tea polyphenols, if occurring, may be through indirect means and/or that the activity may need to be evaluated with longer intervention durations, repeated dosing, or in patients at earlier stages of the disease. PMID- 22044696 TI - Suppressor of cytokine signal 3 and IL28 genetic variation predict the viral response to peginterferon and ribavirin. AB - AIM: The aim of this study was to investigate the relationship among the expression of suppressor of cytokine signaling 3 (SOCS 3) in the liver, the SNPs in the IL28B locus, and the outcome of interferon therapy. METHODS: Prior to interferon treatment, we immunostained 67 liver specimens from chronic hepatitis C (CHC) patients who were receiving peginterferon alpha-2b/ribavirin therapy for suppressor of cytokine signaling 3 (SOCS3), and compared the expression of SOCS3, IL28 polymorphisms and other clinical factors between the patients and compared their eventual outcomes. RESULTS: Significant differences between the low SOCS3 group and high SOCS3 group were found in age, as well as in the platelet, transaminase, gamma-glutamyl transpeptidase levels. The incidence of high SOCS3 was not significantly different between subjects with the TT genotype and the TG genotype (TT : TG = 71%:29%, P = 0.250). In a multivariate analysis, age (>=65 years old) (odds ratio 0.221 [0.120-0.966], P = 0.045), IL28B gene (genotype TT) (odds ratio 5.422 [1.254-23.617], P = 0.024) and SOCS3 (high) (odds ratio 0.308 [0.104-0.948], P = 0.040) were significant predictors of the interferon response. In patients with the TT genotype, those with low SOCS3 immunostaining showed a high sustained virological response (69%), while the sustained virological rate was low (27%) in the patients with high SOCS3 immunostaining. CONCLUSIONS: Using a combination of the SOCS3 immunostained area in the liver and the expression of IL28B single nucleotide polymorphisms might be a useful predictor of hepatitis C virus clearance by interferon therapy. PMID- 22044695 TI - Genetic variants associated with the risk of chronic obstructive pulmonary disease with and without lung cancer. AB - Chronic obstructive pulmonary disease (COPD) is a strong risk factor for lung cancer. Published studies about variations of genes encoding glutathione metabolism, DNA repair, and inflammatory response pathways in susceptibility to COPD were inconclusive. We evaluated 470 single-nucleotide polymorphisms (SNP) from 56 genes of these three pathways in 620 cases and 893 controls to identify susceptibility markers for COPD risk, using existing resources. We assessed SNP- and gene-level effects adjusting for sex, age, and smoking status. Differential genetic effects on disease risk with and without lung cancer were also assessed; cumulative risk models were established. Twenty-one SNPs were found to be significantly associated with risk of COPD (P < 0.01); gene-based analyses confirmed two genes (GCLC and GSS) and identified three additional genes (GSTO2, ERCC1, and RRM1). Carrying 12 high-risk alleles may increase risk by 2.7-fold; eight SNPs altered COPD risk without lung cancer by 3.1-fold and 4 SNPs altered the risk with lung cancer by 2.3-fold. Our findings indicate that multiple genetic variations in the three selected pathways contribute to COPD risk through GCLC, GSS, GSTO2, ERCC1, and RRM1 genes. Functional studies are needed to elucidate the mechanisms of these genes in the development of COPD, lung cancer, or both. PMID- 22044697 TI - Morphologic outer retinal abnormalities in white dot syndromes on spectral-domain optical coherence tomography. PMID- 22044699 TI - Real time triplane echocardiography in the assessment of the functional area of prosthetic aortic valves: reliability and feasibility. AB - PURPOSE: Our study is aimed at evaluating the feasibility and reliability of a simple method for the measurement of the functional area of prosthetic aortic valves (EOA). Three-dimensional echocardiography has proven accurate for left ventricular volume, stroke volume, and aortic valve area measurement. We studied the feasibility and reliability of real time simultaneous triplane echocardiography (RT3P) for assessing the EOA with a fast formula based on the principle of continuity equation, in which we replaced Doppler-derived stroke volume (SV) with SV directly measured with RT3P. METHODS AND RESULTS: EOA of prosthetic aortic valves were measured in 23 consecutive patients requiring periodical follow up. EOA was calculated using Doppler continuity equation (DCE) and the RT3P method by replacing Doppler-derived SV with SV measured with real time triplane echocardiography. We compared functional areas obtained with the two methods with the prosthetic area indicated in the manufacturer's specifications and with the mean transprosthetic gradient. Both methods had a good correlation with the area indicated by the manufacturer. RT3P revealed an inverse correlation between functional area and mean gradient that was better than DCE (P = 0.0359). Inter- and intraobserver variability was not different between the two methods. Execution time was significantly shorter for RT3P. CONCLUSIONS: RT3P is a simple method that can be performed quite rapidly, and can complement the overall assessment of prosthetic valve function. Further studies can confirm our technique. PMID- 22044700 TI - How can benfluorex-related heart valve disease be identified by echocardiography? PMID- 22044698 TI - "Targeted disruption of the epithelial-barrier by Helicobacter pylori". AB - Helicobacter pylori colonizes the human gastric epithelium and induces chronic gastritis, which can lead to gastric cancer. Through cell-cell contacts the gastric epithelium forms a barrier to protect underlying tissue from pathogenic bacteria; however, H. pylori have evolved numerous strategies to perturb the integrity of the gastric barrier. In this review, we summarize recent research into the mechanisms through which H. pylori disrupts intercellular junctions and disrupts the gastric epithelial barrier. PMID- 22044701 TI - A cross-sectional evaluation of venous thromboembolism risk and use of venous thromboembolism prophylaxis in hospitalized patients in Senegal. AB - BACKGROUND: Venous thromboembolism is a common and preventable cause of morbidity and mortality in hospitalized patients. There is a lack of data on the distribution of risk factors and prophylaxis practices in sub-Saharan Africa. AIM: To assess the prevalence of venous thromboembolism risk in hospitalized patients and to determine the proportion of at-risk patients who receive prophylaxis. METHODS: The study was a cross-sectional hospital-based survey. On the basis of the global ENDORSE methodology, patients aged>=40 years admitted to a medical ward or those aged>=18 years admitted to a surgical ward were assessed for risk of venous thromboembolism by hospital chart review. Distribution of risk factors and coverage of prophylaxis in at-risk patients were determined using the 2004 American College of Chest Physicians evidence-based consensus guidelines. RESULTS: From October to November 2008, 520 patients (278 medical; 242 surgical) were enrolled in 12 hospitals across Senegal. Two hundred and ninety-eight (57%) were at risk of venous thromboembolism; 152 (57.4%) medical patients and 146 (60.3%) surgical patients. Among those at risk, 48 (31.6%) medical patients and 52 (35.6%) surgical patients received a prescription for prophylaxis. Among patients without contraindication to anticoagulants, 33.8% (46/136) on medical wards and 37.5% (48/128) on surgical wards received prophylaxis. CONCLUSION: The risk of venous thromboembolism was frequent in hospitalized patients in Senegal but only a few received the recommended prophylaxis. There is a need to implement a programme to improve venous thromboembolism awareness and prophylaxis. PMID- 22044702 TI - Usefulness of serum albumin and serum total cholesterol in the prediction of hospital death in older patients with severe, acute heart failure. AB - BACKGROUND: Acute heart failure (HF) carries high hospital mortality rates in older patients; a multimarker strategy may help identify patients at high risk. AIMS: To investigate prospectively the prognostic relevance of serum albumin and serum total cholesterol (TC) in older patients with severe, acute HF. METHODS: Usual prognostic variables were collected on admission in 207 consecutive patients aged>70 years with severe, acute HF. Serum albumin and serum TC were obtained soon after clinical improvement. RESULTS: Hospital mortality rate was 19%. Patients who died were similar to patients who survived in terms of age, sex, heart rate, serum haemoglobin and left ventricular ejection fraction. Patients who died had higher concentrations of B-type natriuretic peptide (BNP), blood urea nitrogen, serum creatinine, C-reactive protein and serum troponin I, lower systolic blood pressure, and lower concentrations of serum albumin and serum TC than patients who survived (P<0.01 for all). Serum albumin was the best independent predictor of hospital death (odds ratio 0.82 [0.74-0.90], P<0.001), with blood urea nitrogen (P=0.02) and log (BNP) (P=0.02). A simple risk score based on serum albumin (<3g/dL; 2 points), BNP (>840pg/mL; 1 point) and blood urea nitrogen (>15.3mmol/L; 1 point) discriminated patients without (score 0 to 1, hospital death 4%) from patients with (score 2 to 4, hospital death 35%, P<0.001) a high risk of death. CONCLUSION: Hypoalbuminaemia offers powerful additional prognostic information to usual prognostic variables in older patients with severe, acute HF, and deserves further attention in multimarker strategies. PMID- 22044703 TI - Evolution of acute coronary syndrome with normal coronary arteries and normal cardiac magnetic resonance imaging. AB - BACKGROUND: Acute coronary syndrome (ACS) with normal coronary angiography is a frequent clinical situation with an uncertain prognosis. Cardiac magnetic resonance imaging (CMRI) is a powerful tool for differential diagnosis between myocardial infarction (MI), acute myocarditis and Tako-tsubo cardiomyopathy (TTC). Data are sparse regarding the evolution of patients presenting an ACS with normal coronary arteries and normal CMRI. AIMS: To evaluate the evolution of patients presenting an ACS with normal coronary arteries and normal CMRI, with a 1-year follow-up. METHODS: Eighty-seven consecutive patients (mean age, 53 years; 40.2% men) presenting an ACS with troponin elevation and normal coronary arteries by angiography were prospectively included. All patients underwent CMRI at 3 Tesla. Adverse events were recorded with 1-year follow-up. RESULTS: A likely aetiology for the acute clinical presentation was established by CMRI in 63.2% of patients (22.7% MI, 26.4% acute myocarditis, 11.5% TTC). During follow-up, one patient in the MI group had a stroke (1.2%). In the myocarditis group, there was one initial cardiogenic shock, one episode of congestive heart failure (1.2%) and nine patients had recurrent chest pain without troponin elevation (10.3%). Two TTC group patients initially presented with cardiogenic shock (2.4%); there were no other adverse events in this group during follow-up. In the remaining 36.7% patients, no clear diagnosis could be identified by CMRI, and no adverse events occurred during follow-up. CONCLUSION: CMRI is a useful tool for the management of ACS presenting with normal coronary angiography, as it helps to ascertain the diagnosis and adapt treatment in a large proportion of cases. Nonetheless, patients with no abnormalities identified by CMRI have an excellent evolution. PMID- 22044704 TI - Vascular function and mortality in haemodialysis patients: a pilot study. AB - BACKGROUND: Haemodialysis patients often have impaired vascular function that can contribute to mortality. Endothelial-dependent and -independent vascular function can be assessed using the brachial artery reactivity (BAR) technique that measures flow-mediated dilatation (FMD) and the response to glyceryl trinitrate (GTN), respectively. AIMS: The aim of this pilot study was to determine whether BAR measurements in haemodialysis patients were associated with mortality. METHODS: Brachial artery responses to FMD and administration of GTN were assessed in consecutive haemodialysis patients. Patients were then followed up to 18 months after BAR measurements. RESULTS: Seventeen patients were included in the study. After 18 months of follow-up, patients were divided into two groups: survived (n=12) and deceased (n=5). Patients who survived had a significantly greater median percentage vasodilatation to GTN than those who died (19.1% vs 8.8%; P=0.04); and a significantly greater median area under the diameter change time curve (318 vs 146 mm/s; P=0.03). However, there were no significant differences between survivors and deceased in median percentage vasodilation to FMD (6.0% vs 4.3%; P=0.21), time to peak dilation (45 vs 40s; P=0.66) or area under the diameter change-time curve (35.5 vs 20 mm/s; P=0.29). CONCLUSION: In this pilot study in a small group of haemodialysis patients, endothelial independent vasodilatory response to GTN was associated with mortality and was of better prognostic value than the endothelial-dependent response to FMD. This finding needs to be investigated in a larger cohort. PMID- 22044705 TI - Diagnostic accuracy of quantitative heart-fatty acid binding protein assays compared with Cardiodetect((r)) in the early detection of acute coronary syndrome. AB - BACKGROUND: Heart-fatty acid binding protein (h-FABP) has been proposed as a cardiac marker for the early detection of acute coronary syndrome (ACS). In a study of 677 patients admitted to the emergency department (ED) for chest pain, we found that a semiquantitative point-of-care test that detects h-FABP (Cardiodetect((r))) had low sensitivity for the prediction of ACS. OBJECTIVE: The aim of this ancillary study was to analyze and compare the performance of h-FABP for early ACS diagnosis in this large cohort of unselected patients, using a quantitative immunoassay and Cardiodetect((r)). METHODS: h-FABP was measured with a ready-to-use, solid-phase, enzyme-linked immunosorbent assay (ELISA) in 677 patients admitted to the ED with chest pain and suspected non-ST-segment elevation ACS. Two physicians, blinded to the results of the marker, categorized patients as having or not having non-ST-segment elevation ACS. RESULTS: Non-ST segment elevation ACS was diagnosed in 185 patients (27.3%). The median h-FABP level was higher in patients with ACS (1.36MUg/L, interquartile range [IQR] 0.59 3.55) than in those without ACS (0.58MUg/L, IQR 0.24-1.34; P<0.01). The area under the curve was 0.68 (95% confidence interval [CI] 0.63-0.73). h-FABP did not improve the performance of a model that included the usual diagnostic tools for ACS management (odds ratio 0.92, 95% CI 0.32-2.70). The classification agreement between the ELISA and Cardiodetect((r)) was 92.1% (kappa 0.39). CONCLUSION: In this study, we confirmed that measurement of h-FABP was insufficient to be used as a marker of ACS and NSTEMI in ED, whatever the analytical technique used. PMID- 22044706 TI - Characteristics of isolated atrial flutter versus atrial flutter combined with atrial fibrillation. AB - BACKGROUND: Atrial flutter (AFL) and atrial fibrillation (AF) are "fellow travellers". AF may be a stable, "isolated" rhythm, a bridge between sinus rhythm and AF, or both arrhythmias can coexist. Whether the characteristics of isolated AFL are different from those of patients with AFL combined with AF is still unclear. AIM: To compare the clinical characteristics of patients with isolated AFL to those of patients with AFL combined with AF, in a series of patients referred for AFL ablation. METHODS: Seventy-six consecutive patients (mean age 66.9+/-12.2 years; 53 men) with a history of electrocardiogram-documented paroxysmal or persistent AFL, referred for catheter ablation, underwent clinical work-up including bidimensional echocardiogram. Patients were subdivided into group I (44 with isolated AFL) and group II (32 with AFL and a history of AF). RESULTS: Underlying heart disease was present in 62 patients (81.6%). Hypertension was the most common cardiac disorder (n=44, 57.9%) and was more prevalent in group II than in group I (75.0% vs 45.5%; P=0.01). Prevalence of prior cardiac surgery was higher in group I (22.7% vs 6.3%; P=0.04). AFL was persistent in 35 group I patients and 17 group II patients (79.5% vs 53.1%; P=0.01). Class I or III antiarrhythmic drug use was more frequent in group II (84.4% vs 45.5%; P=0.001). CONCLUSION: This study showed significant differences between patients with isolated AFL and those with AFL combined with AF, in the prevalence of underlying heart disease and the use of antiarrhythmic medication, which were higher when both atrial arrhythmias were combined. In turn, the history of cardiac surgery (including atriotomy), was more common in patients with isolated AFL than in those with AFL combined with AF. PMID- 22044707 TI - Update on the medical treatment of stable angina. AB - Stable angina is a form of coronary artery disease. Its potential to progress requires the most appropriate treatment in order to reduce the incapacitating effect of an acute angina attack and to avoid long-term cardiovascular events. With or without revascularization, pharmacological treatment is an essential component of this treatment strategy, which also involves lifestyle and diet. Statins and aspirin have been shown to be effective in preventing different aspects of coronary artery disease overall. The efficacy of other classes of treatment has been demonstrated in contexts such as stable angina (including postmyocardial infarction) and heart failure (under specific conditions of dosing) for beta-blockers and in contexts such as heart failure, postinfarction and following revascularization for angiotensin-converting enzyme inhibitors. Along with the oldest classes of treatment, such as nitrates (and related derivatives), beta-blockers and calcium channel blockers, new classes of treatments with entirely (trimetazidine, ivabradine) or partly (nicorandil) different mechanisms of action have now been added. The latest antianginal to obtain marketing authorization, ranolazine, is not yet available in France. The different levels of evidence of the efficacy of these pharmacological products vary greatly and overall are higher for those developed most recently. None is devoid of side effects, which must be taken into account in these patients, many of whom are elderly and polymedicated. PMID- 22044708 TI - An unusual cause of systolic murmur. PMID- 22044709 TI - Use of umbilical venous catheter before performing Rashkind's procedure. PMID- 22044710 TI - Unusual monocoronary system and sudden death. PMID- 22044711 TI - Incidentally found double-orifice mitral valve in an elderly patient. PMID- 22044712 TI - Police encounters with people with intellectual disability: prevalence, characteristics and challenges. AB - BACKGROUND: This study investigated the experiences and perceptions of operational members of Victoria Police in relation to their contacts with people with intellectual disability (ID). Key interests for exploration included how frequently and in what context police reported coming into contact with people with ID, how they made this identification, and the challenges they experienced at this interface. METHODS: Participants comprised 229 operational police members who attended mandatory firearms training sessions over a 2-week period in Melbourne, Australia. RESULTS: Police reported coming into contact with people they believed to have an ID on a regular basis and for a wide variety of reasons. They were most likely to base their knowledge on job-related experiences and were most likely to identify individuals on the basis of physical and behavioural cues. The most common challenges were communication, and gaining access to assistance and co-operation from other service providers. While many considered themselves capable in their interactions with those with ID, those who identified that they were most in need of training reported lower confidence in how to respond in these encounters. CONCLUSIONS: Future training needs to focus on differentiating between mental illness and ID, techniques for enhancing identification and communication, and the inclusion of hands-on scenario-based sessions involving an interdisciplinary approach. PMID- 22044713 TI - Examining the stable door after the horse has bolted: why is EIA such a challenge? PMID- 22044714 TI - Immunological differences in the global release of the major cat allergen Fel d 1 are influenced by sex and behaviour. AB - The biological function of Fel d 1, the major cat allergen released in the environment, is still unclear despite studies suggesting a putative role in chemical communication. Structural and immunological polymorphisms of Fel d 1 have been described. This study examined how Fel d 1 immunological polymorphism may have a physiological origin by estimating a potential relationship with the sex of cats and cat-human interactions. Samples from bath washes of 21 cats were screened to study antibody binding to Fel d 1 using an ELISA. Personality and Tolerance Handling scores were used to assess the behaviour of the cats. In the washes, Fel d 1 concentrations were significantly lower in females than in males (P<0.05). Slopes from the ELISA dose-dependent curves varied among the cats: males secreted Fel d 1 variants with higher antibody recognition than females (P<0.01). Females that were aggressive and difficult to handle displayed a diminished slope value, and therefore a weaker Fel d 1 immunoreactivity in global washes, compared to females that were sociable (P=0.09) and easy to handle (P=0.07). This study shows a variable immunological polymorphism of Fel d 1 within a cat population, particularly between males and females, and this polymorphism appears to be related to cat-human interactions. PMID- 22044715 TI - The developmental sequence of tobacco withdrawal symptoms of wanting, craving and needing. AB - OBJECTIVE: The first case series on tobacco addiction suggested that withdrawal symptoms evolve through a clear developmental sequence both over the clinical course and during an episode of abstinence. The objective of the current study was to determine if this observation would be confirmed by a second case series. METHODS: The subjects were 25 adolescent and adult smokers. Subjects were provided with operational definitions of the withdrawal symptoms of wanting, craving and needing. Using nondirective techniques, detailed histories of subjects' experiences with these three symptoms during abstinence from tobacco were obtained in individual interviews. RESULTS: All 25 subjects identified the operational definitions of wanting and craving as symptoms they had experienced, and 21 subjects indicated that the definition of needing described a symptom they had experienced. All 25 subjects reported that wanting was the first symptom they had experienced; 24 of 25 subjects reported that craving was the second symptom experienced; and 20 of the 21 subjects that had experienced needing reported that this was the third symptom they had experienced. All subjects reported that during abstinence symptoms appeared in the order of wanting, craving and needing. Subjects reported that stress-induced urges to smoke are not relieved by smoking, do not follow a characteristic sequence, and do not have a latency. CONCLUSIONS: Abstinence from tobacco provokes characteristic symptoms of wanting, craving and needing that are widely endorsed by smokers as symptoms they have experienced. These symptoms develop in a set sequence of wanting, craving and needing in all, or nearly all, smokers over their clinical course. These symptoms recur in the same sequence during acute episodes of abstinence. Smokers can distinguish between four symptoms: wanting, craving, needing and stress-induced urges to smoke, but these distinctions are not captured by generic 'craving' measures. PMID- 22044716 TI - Assessment of risk factors related to healthcare-associated methicillin-resistant Staphylococcus aureus infection at patient admission to an intensive care unit in Japan. AB - BACKGROUND: Healthcare-associated methicillin-resistant Staphylococcus aureus (HA MRSA) infection in intensive care unit (ICU) patients prolongs ICU stay and causes high mortality. Predicting HA-MRSA infection on admission can strengthen precautions against MRSA transmission. This study aimed to clarify the risk factors for HA-MRSA infection in an ICU from data obtained within 24 hours of patient ICU admission. METHODS: We prospectively studied HA-MRSA infection in 474 consecutive patients admitted for more than 2 days to our medical, surgical, and trauma ICU in a tertiary referral hospital in Japan. Data obtained from patients within 24 hours of ICU admission on 11 prognostic variables possibly related to outcome were evaluated to predict infection risk in the early phase of ICU stay. Stepwise multivariate logistic regression analysis was used to identify independent risk factors for HA-MRSA infection. RESULTS: Thirty patients (6.3%) had MRSA infection, and 444 patients (93.7%) were infection-free. Intubation, existence of open wound, treatment with antibiotics, and steroid administration, all occurring within 24 hours of ICU admission, were detected as independent prognostic indicators. Patients with intubation or open wound comprised 96.7% of MRSA-infected patients but only 57.4% of all patients admitted. CONCLUSIONS: Four prognostic variables were found to be risk factors for HA-MRSA infection in ICU: intubation, open wound, treatment with antibiotics, and steroid administration, all occurring within 24 hours of ICU admission. Preemptive infection control in patients with these risk factors might effectively decrease HA-MRSA infection. PMID- 22044717 TI - Initial survival data of kidney transplant patients with pre-transplant monoclonal gammopathy. AB - BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is the presence of a serum monoclonal protein at a concentration of <3 g/dL without evidence of lymphoproliferative disease or organ damage. The prevalence of MGUS in kidney transplantation (KT) candidates is unknown. The present is a retrospective report of patients who underwent evaluation for a KT and were found to have MGUS at our center. METHODS: All transplant candidates found to have MGUS between the years 2000 and 2007 were included. Variables were collected. Patients with MGUS that received a KT were compared with patients with MGUS that were not transplanted. RESULTS: Of a total of 1215 KT candidates, 34 were found to have MGUS during the KT evaluation. Nine patients with MGUS were transplanted. Myeloma or lymphoproliferative disease was not observed. Following transplantation, the MGUS group had a lower survival than the non-transplanted group. However, survival from the time of MGUS diagnosis was not different between the transplanted and non-transplanted MGUS groups. CONCLUSIONS: In this group, transplantation did not confer a survival benefit. It is our hope that these initial data will serve as a platform for future studies. We suggest MGUS screening in all patients older than 50 yr of age undergoing evaluation for transplantation. PMID- 22044718 TI - Antibacterial activities of selected Cameroonian spices and their synergistic effects with antibiotics against multidrug-resistant phenotypes. AB - BACKGROUND: The emergence of multi-drug resistant (MDR) phenotypes is a major public health problem today in the treatment of bacterial infections. The present study was designed to evaluate the antibacterial activities of the methanol extracts of eleven Cameroonian spices on a panel of twenty nine Gram negative bacteria including MDR strains. METHODS: The phytochemical analysis of the extracts was carried out by standard tests meanwhile the liquid micro-broth dilution was used for all antimicrobial assays. RESULTS: Phytochemical analysis showed the presence of alkaloids, phenols and tannins in all plants extracts. The results of the antibacterial assays indicated that all tested extracts exert antibacterial activities, with the minimum inhibitory concentration (MIC) values varying from 32 to 1024 MUg/ml. The extracts from Dichrostachys glomerata, Beilschmiedia cinnamomea, Aframomum citratum, Piper capense, Echinops giganteus, Fagara xanthoxyloides and Olax subscorpioidea were the most active. In the presence of efflux pump inhibitor, PAbetaN, the activity of the extract from D. glomerata significantly increased on 69.2% of the tested MDR bacteria. At MIC/5, synergistic effects were noted with the extract of D. glomerata on 75% of the tested bacteria for chloramphenicol (CHL), tetracycline (TET) and norfloxacin (NOR). With B. cinnamomea synergy were observed on 62.5% of the studied MDR bacteria with CHL, cefepime (FEP), NOR and ciprofloxacin (CIP) and 75% with erythromycin (ERY). CONCLUSION: The overall results provide information for the possible use of the studied extracts of the spices in the control of bacterial infections involving MDR phenotypes. PMID- 22044719 TI - Peripheral regulation by ecdysteroids of olfactory responsiveness in male Egyptian cotton leaf worms, Spodoptera littoralis. AB - Physiological and behavioral plasticity allows animals to adapt to changes in external (environmental) and internal (physiological) factors. In insects, the physiological state modulates adult behavior in response to different odorant stimuli. Hormones have the potential to play a major role in the plasticity of the olfactory responses. To explore if peripheral olfactory processing could be regulated by steroid hormones, we characterized the molecular, electrophysiological, and behavioral response to changes in endogenous hormone levels in adult male Spodoptera littoralis. The expression of the receptor complex (EcR/USP) was localized by in situ hybridization in the olfactory sensilla of antennae. Injections of 20-hydroxyecdysone (20E) induced an ecdysteroid signaling pathway in antennae and increased expression of the nuclear receptors EcR, USP and E75. Diacylglycerol kinase (DGK) and CaM expression were also up-regulated by 20E. Taken together, these molecular, electrophysiological, and behavioral results suggest a hormonal regulation of the peripheral olfactory processing in S. littoralis. PMID- 22044720 TI - KHA-CARI guideline: biochemical and haematological targets: haemoglobin concentrations in patients using erythropoietin-stimulating agents. PMID- 22044721 TI - Human leukocyte antigen-G 3' untranslated region polymorphisms are associated with better kidney allograft acceptance. AB - Human leukocyte antigen-G (HLA-G) plays a well-recognized role in the modulation of the immune response, and HLA-G expression has been associated with increased graft survival and decreased rejection episodes. To investigate the role of the HLA-G 3' untranslated region (3'UTR) in renal transplantation, we evaluated several polymorphic sites (14-bp Del/Ins +3003T/C, +3010C/G, +3027C/A, +3035C/T, +3142G/C, and +3187A/G) in patients exhibiting or not exhibiting rejection episodes. A total of 104 patients (15 with acute and 48 with chronic rejection, and 41 with no rejection) and 142 healthy individuals were studied. HLA-G 3'UTR was typed by direct sequencing. The +3035C-C genotype was more frequent in patients exhibiting chronic rejection compared with healthy controls, and the +3035C-T genotype was less frequent in chronic rejection compared with patients without rejection (acute plus chronic) or compared with healthy controls. The +3187G-A genotype, in which the A allele is associated with increased mRNA degradation, showed increased frequency in the rejection group (acute plus chronic) when compared with healthy controls. The 14 base pair Deletion/Insertion genotype was marginally increased in patients with acute rejection. This is the first study to show associations among numerous polymorphic sites in the HLA-G 3'UTR in kidney allotransplantation, which may contribute to the understanding of HLA-G post-transcriptional mechanisms. PMID- 22044722 TI - Epidural varicosis as a possible cause of radicular pain: a case report. AB - INTRODUCTION: The incidence rate of epidural varicosis has declined by 0.07% to 1.2% since the introduction of computed tomography and magnetic resonance imaging. Despite the use of these modern imaging methods it can still be difficult to distinguish the diagnosis of epidural varicosis from other causes, such as nucleus pulposus prolapse. CASE PRESENTATION: We present the case of a 48 year-old Caucasian woman who had been experiencing sciatic pain for seven years. A physical examination showed nerve root pain at L5 on the right side, with positive signs of neurotension. During an elective hysterectomy due to endometriosis, unusually pronounced varicosis in her lesser pelvis was seen that had not previously been detected. Postoperatively, our patient developed a symptomatic pulmonary embolism. Findings from magnetic resonance tomography of her lumbar spine, in conjunction with our patient's history, were considered by the radiologist to be indicative of epidural varicosis. No further pathological abnormalities that could have been the cause of the nerve root pain were found. CONCLUSIONS: In cases of epidural varicosis with irritation of neural structures as a result of inferior vena cava hypoplasia, surgical treatment leads to unsatisfactory results. Significantly better results can be achieved by resolving the cause of the vena cava pathology. In cases of hypoplasia or aplasia of the inferior vena cava this is not always possible; consequently, as in the case of our patient, only a symptomatic therapy in combination with an anticoagulant and compression therapy can be performed. PMID- 22044723 TI - Generation of the first BAC-based physical map of the common carp genome. AB - BACKGROUND: Common carp (Cyprinus carpio), a member of Cyprinidae, is the third most important aquaculture species in the world with an annual global production of 3.4 million metric tons, accounting for nearly 14% of the all freshwater aquaculture production in the world. Apparently genomic resources are needed for this species in order to study its performance and production traits. In spite of much progress, no physical maps have been available for common carp. The objective of this project was to generate a BAC-based physical map using fluorescent restriction fingerprinting. RESULT: The first generation of common carp physical map was constructed using four- color High Information Content Fingerprinting (HICF). A total of 72,158 BAC clones were analyzed that generated 67,493 valid fingerprints (5.5 * genome coverage). These BAC clones were assembled into 3,696 contigs with the average length of 476 kb and a N50 length of 688 kb, representing approximately 1.76 Gb of the common carp genome. The largest contig contained 171 BAC clones with the physical length of 3.12 Mb. There are 761 contigs longer than the N50, and these contigs should be the most useful resource for future integrations with linkage map and whole genome sequence assembly. The common carp physical map is available at http://genomics.cafs.ac.cn/fpc/WebAGCoL/Carp/WebFPC/. CONCLUSION: The reported common carp physical map is the first physical map of the common carp genome. It should be a valuable genome resource facilitating whole genome sequence assembly and characterization of position-based genes important for aquaculture traits. PMID- 22044724 TI - Short women with severe sepsis-related acute lung injury receive lung protective ventilation less frequently: an observational cohort study. AB - INTRODUCTION: Lung protective ventilation (LPV) has been shown to improve survival and the duration of mechanical ventilation in acute lung injury (ALI) patients. Mortality of ALI may vary by gender, which could result from treatment variability. Whether gender is associated with the use of LPV is not known. METHODS: A total of 421 severe sepsis-related ALI subjects in the Consortium to Evaluate Lung Edema Genetics from seven teaching hospitals between 2002 and 2008 were included in our study. We evaluated patients' tidal volume, plateau pressure and arterial pH to determine whether patients received LPV during the first two days after developing ALI. The odds ratio of receiving LPV was estimated by a logistic regression model with robust and cluster options. RESULTS: Women had similar characteristics as men with the exception of lower height and higher illness severity, as measured by Acute Physiology and Chronic Health Evaluation (APACHE) II score. 225 (53%) of the subjects received LPV during the first two days after ALI onset; women received LPV less frequently than men (46% versus 59%, P < 0.001). However, after adjustment for height and severity of illness (APACHE II), there was no difference in exposure to LPV between men and women (P = 0.262). CONCLUSIONS: Short people are less likely to receive LPV, which seems to explain the tendency of clinicians to adhere to LPV less strictly in women. Strategies to standardize application of LPV, independent of differences in height and severity of illness, are necessary. PMID- 22044725 TI - Unusual systemic metastases of malignant seminoma in a dog. AB - Unilateral enlargement of left testicle and scrotum was detected in an 8-year-old West Highland White Terrier. The histopathological diagnosis after surgery was a seminoma (SEM) tumour, and a diagnosis of metastatic foci was also detected in vaginal tunic and scrotum. Two months later, new metastatic SEM foci in the skin were diagnosed. Twenty-two months after the initial orchiectomy new multiple cutaneous nodules and a swelling of periesophageal structures were observed. Finally, the necropsy revealed multiple malignant metastatic SEM focus. To the author's knowledge, this is the first description of a canine SEM with unusual widespread metastasis on the base of tongue, soft palate, trachea and pericardium. PMID- 22044726 TI - A novel method to detect accidental oesophageal intubation based on ventilation pressure waveforms. AB - BACKGROUND: Emergency endotracheal intubation results in accidental oesophageal intubation in up to 17% of patients. This is frequently undetected thereby adding to the morbidity and mortality. No current method to detect accidental oesophageal intubation in an emergency setting is both highly sensitive and specific. We hypothesized that, based on differences between the mechanical properties of the oesophagus and the trachea/lung, ventilation pressures could discriminate between tracheal and oesophageal intubation. Such a technique would potentially not suffer some of the limitations of current methods to detect oesophageal intubation in emergency conditions such as noisy environment (making clinical assessment difficult) or low/no flow states (reducing the applicability of capnometry). The aim of our study was thus to develop and assess a technique that may more rapidly and accurately differentiate oesophageal from tracheal intubation based on airway pressure gradients. MATERIALS AND METHODS: Forty adult patients undergoing elective surgery were included. In 20 patients the trachea was intubated with an endotracheal tube; in 20 patients the oesophagus was purposefully intubated using an Easytube((r)) (Rush, Germany). In all patients, a thin air-filled catheter was inserted through the tube lumen until its tip was 1cm from the distal end, and connected to a pressure transducer. Pressure was recorded simultaneously from a second catheter at the proximal end of the tube. For the first three manual ventilations in each patient, a parameter (D) based on temporal (dP/dt) and spatial (dP/ds) pressure gradients (and reflecting flow divided by elastance) was calculated and evaluated for its ability to discriminate between oesophageal and tracheal intubation. RESULTS AND DISCUSSION: For all tracheal ventilations, D-values were >0.5 (range 0.6-47.9), while for all oesophageal ventilations D-values were <0.5 (range 0.0005-0.07). CONCLUSION: This technique has the potential to provide a diagnosis of failed intubation within seconds with high sensitivity and specificity. PMID- 22044727 TI - Differential diagnosis and therapy of leg ulcers. AB - A leg ulcer is a symptom and the treating physician needs to find out its origin by differential diagnostic approaches and procedures. The correct diagnosis leads to a specific therapy that ideally accelerates the healing of the ulceration. Identifying the pathogenesis of a leg ulcer is the first and main step towards healing. Although vascular diseases are the major causes of leg ulcers, one needs to consider, in addition to venous and arterial disorders, autoimmune, infectious, metabolic and neoplastic causes. The simple truth that one can only make a diagnosis that was considered holds particularly true in leg ulcers. The differential diagnostic considerations presented here appear in the daily routine of a dermatologist and the article provides help in diagnostic approaches and therapeutic decisions. PMID- 22044728 TI - The role of ultrasonography in the diagnosis of the musculo-skeletal problems of haemophilia. AB - Recurrent haemarthrosis is the final cause of haemophilic arthrosic disease in haemophilia patients. Therefore, it is essential to diagnose it early, both clinically and by imaging. In addition, haemophilia patients experience chronic synovitis, joint degeneration, muscle haematoma and pseudotumours. The objective of this article is to highlight the value of ultrasounds in the diagnosis and control of the evolution of musculo-skeletal problems in haemophilia patients. To this end, we have performed a literature search in the PubMed, Web of Science((r)) (WOS) and SciVerse bases, using the following keywords: hemophilia or haemophilia and ultrasonography (US), ultrasound, echography and sonography. The search was limited to studies published in English between the years 1991 and 2011, finding a total of 221 references. After reviewing the title or abstract for evidence of the use of US for the diagnosis of musculo-skeletal lesions in haemophilia, we selected 24 of these references. We added data collected from our experience to the most important data found in the references. Our main conclusion is that US is highly valuable for the diagnosis of musculo-skeletal diseases in haemophilia. It is a fast, effective, safe, available, comparative, real-time technique that can help us confirm the clinical examination. It is particularly important in acute haemarthrosis, as it can be used to objectively identify the presence of blood in the joints, measure its size, pinpoint its location, assess its evolution and confirm its complete disappearance. PMID- 22044729 TI - Left ventricular function and exercise capacity in patients with slow coronary flow. AB - BACKGROUND: Endothelial and microvascular dysfunction have been implicated in slow coronary flow (SCF). How and to what extent do these etiological factors affect left ventricular (LV) function and exercise capacity? AIM: The aim of the study was to evaluate LV systolic and diastolic function by pulsed tissue Doppler imaging (TDI) in SCF patients and their effects on exercise capacity. SUBJECTS AND METHODS: Sixty SCF patients and 20 control subjects were included in the study. Echocardiographic examination, treadmill exercise test, and TDI were performed. Isovolumic myocardial acceleration (IVA) and myocardial performance index (MPI) were measured. RESULTS: TDI mean parameters for systolic and diastolic LV function were significantly impaired in SCF group with decreased Sa, IVA, Ea/Aa, and increased MPI (0.31 +/- 0.06 vs. 0.26 +/- 0.04, P < 0.01) compared to control. There was significant correlation between thrombolysis in myocardial infarction (TIMI) frame count and TDI mean parameters for LV systolic function (Sa & IVA, r =-0.53, P < 0.01 & r =-0.36, P < 0.05, respectively). Mean TIMI frame count was correlated with MPI and E/Ea. SCF patients had poorer peak exercise capacity than the controls (9.9 +/- 1.9 METs vs. 12.7 +/- 2.3, P < 0.01) with significant negative correlation with mean TIMI frame count (r =-0.46, P < 0.01). CONCLUSION: There is impairment of LV systolic and diastolic function in SCF patients with clinical impact on exercise capacity which emphasizes the importance of close follow-up of these patients for risk stratification. PMID- 22044730 TI - Novel scoring system as a useful model to predict the outcome of patients with acute liver failure: Application to indication criteria for liver transplantation. AB - AIM: In Japan, the indication for liver transplantation in patients with acute liver failure (ALF) is currently determined according to the guideline published in 1996. However, its predictive accuracy has fallen in recent patients. Thus, we attempted to establish a new guideline. METHODS: The subjects were 1096 ALF patients enrolled in a nationwide survey. All patients showed a prothrombin time <40% of the standardized value and grade II or more severe hepatic encephalopathy. A multiple logistic regression analysis and receiver operating characteristic analysis were performed in 698 patients seen between 1998 and 2003 to identify significant parameters determining the outcome of patients. The extracted parameters were graded as numerical scores. An established scoring system was validated in patients seen between 2004 and 2008. RESULTS: Six parameters were identified and graded as 0, 1 and/or 2; the interval between disease onset and development of hepatic encephalopathy, prothrombin time, serum total bilirubin concentration, the ratio of direct to total bilirubin concentration, peripheral platelet count and the presence of liver atrophy. When the prognosis of the patients with total score of 5 or more was judged as "death", the predictive accuracy was 0.80 with sensitivity, specificity, positive predictive value and negative predictive value greater than 0.70. The values were similarly high in patients for validation. CONCLUSION: Novel scoring system for predicting the outcome of ALF patients may be useful to determine the indication of liver transplantation, since the system showed high predictive accuracy even after validation. PMID- 22044731 TI - I-Stent for treatment of angle recession with raised intraocular pressure. PMID- 22044732 TI - Effect of high hydrostatic pressure processing on norovirus infectivity and genome stability in strawberry puree and mineral water. AB - We report an evaluation of the effect of various combinations of pressures and times on the inactivation of norovirus (NoV) in two types of matrices that are important in NoV transmission: water and soft fruits. The human NoV surrogate murine norovirus was used as the model virus. The effect of HHP on the viral genome was evaluated by using RT real-time PCR (RT-qPCR), and infectivity assay was used to assess effects on the ability of the virus to attach to and replicate in cells. HHP treatments of 400 MPa for 2.5 min proved to be sufficient for efficient inactivation of NoV (>99.9% reduction). The efficacy of viral inactivation was highly dependent on the matrix in which the virus was present. Therefore, the effect of HHP should be carefully studied in all matrices to which HHP could potentially be applied. Finally, we found no consistent correlation between RT-qPCR and virus infectivity results, and consequently RT-qPCR is not a satisfactory tool for predicting risks to human health. PMID- 22044733 TI - Bond strength and interfacial micromorphology of etch-and-rinse and self-adhesive resin cements to dentin. AB - PURPOSE: To evaluate the microtensile bond strength and interfacial micromorphology of indirect composite restorations to dentin using three commercial resin cements after 24 hours and 30 days of water storage. MATERIALS AND METHODS: The medium dentin of third human molars was exposed (N = 30, n = 10 per group). Three commercial resin cements were used to cement indirect resin composite restorations to dentin: the auto-cured C&B Cement/All Bond 2, the dual cured RelyX ARC/Adper Single Bond 2, and the self-adhesive dual-cured RelyX Unicem. Teeth were sectioned after water storage at 37 degrees C (24 hours and 30 days) to obtain beams with a bonded area of 0.8 mm(2) . The specimens were tested in a universal testing machine at a 0.5 mm/min crosshead speed. Scanning electron microscopic fractographic and interfacial micromorphology analyses were performed. Data were analyzed using two-way ANOVA and Tukey's test (alpha= 0.05). RESULTS: Mean bond strength (MPa) after 24 hours: C&B Cement 19.5 +/- 3.8, RelyX ARC 40.8 +/- 9.4, RelyX Unicem 31.3 +/- 7.4; after 30 days: C&B Cement 24.5 +/- 5.1, RelyX ARC 44.2 +/- 8.5, RelyX Unicem 28.3 +/- 7.1. The mean bond strengths of both dual-cure cements were significantly higher than that obtained with C&B Cement after 24 hours. A significant increase in the bond strength of C&B Cement was verified after 30 days, reaching values statistically equivalent to those produced by RelyX Unicem and RelyX ARC. The self-adhesive cement preserved the same level of bond strength after 30 days. Fractographic analysis revealed a prevalence of cohesive fractures in the hybrid layer for C&B Cement, mixed (cohesive in the cement, hybrid layer, and adhesive) for RelyX ARC, and cohesive in the cement for RelyX Unicem. No distinguishable hybrid layer or resin tags were observed in the interaction of RelyX Unicem with dentin. CONCLUSIONS: The particular interaction of each cement with dentin results in specific bond strength and failure patterns that varied among groups in both evaluation times. Even though the self-adhesive cement tested exhibited no authentic hybrid layer, it was able to promote reliable adhesion with the underlying dentin. PMID- 22044734 TI - Cognitive symptoms are common in immune thrombocytopenia and associate with autonomic symptom burden. AB - OBJECTIVES: People with adult immune thrombocytopenia (ITP) are commonly thought to have an isolated blood disorder, but many also describe memory and concentration problems. Cognitive impairment commonly associates with autonomic dysfunction. Here, we quantified cognitive symptoms in a large cohort of patients with ITP compared with controls and explored the relationship with autonomic symptoms. METHODS: Patients with ITP were approached in the UK via the national ITP Support Association and invited to complete Composite Autonomic Symptom Scale (COMPASS; measure of autonomic symptoms) and Cognitive Failures Questionnaire (CFQ) together with one from a friend of similar age and sex without ITP. RESULTS: Three hundred and ninety-eight patients with ITP completed measures with paired data from a representative group of 189 patients and controls (47%). Both autonomic and cognitive symptom burden were higher in ITP compared with controls (COMPASS score (48 +/- 14 vs. 38 +/- 12; P > 0.0001); CFQ (43 +/- 17 vs. 36 +/- 13; P < 0.0001). A positive relationship was seen between increasing cognitive symptoms and higher COMPASS score (P < 0.0001; r(2) = 0.1). Increasing cognitive symptoms did not associate with platelet count (P = 0.08, r(2) = 0.008). Multivariate analysis confirmed age and COMPASS independently associated with higher CFQ but not platelet count. CONCLUSION: Immune thrombocytopenia is more than a bleeding disorder; cognitive symptoms are common and independently associate with autonomic symptoms but not disease severity. PMID- 22044735 TI - Silencing of ICERs (Inducible cAMP Early Repressors) results in partial protection of neurons from programmed cell death. AB - ICERs proteins (Inducible cAMP Early Repressors) are the most effective endogenous repressors of CREB/CREM/ATF transcription factors family (CREB-cAMP Responsive Element Binding protein, CREM-cAMP Responsive Element Modulator, ATF Activating Transcription Factor) that have repeatedly been shown to have a prosurvival function. It has been reported previously that neuronal death is accompanied by increased expression of ICERs and, furthermore, their overexpression provokes neuronal cell death in culture. However, it was not explained whether endogenously activated by proapoptotic stimuli ICERs contribute to the neuronal cell death. Herein, we have examined the involvement of endogenous ICERs in the apoptosis by checking whether it is possible to protect neurons from cell death by blocking the ICER gene. We applied two different in vitro models of neuronal death of primary neuronal cultures: excitotoxic death of neurons derived from dentate gyrus, and cortical cell loss provoked by trophic deprivation. Using the lentiviral vector (LV) to deliver shRNA, specifically silencing ICERs, but not other CREM proteins, we have found that silencing of ICERs enhances the CRE-driven transcription and exerts a mild, although significant, neuroprotective effect in both models. Since we demonstrated that silencing of endogenous ICERs have protective effect on neurons exposed to apoptosis-provoking conditions, targeting ICERs might be a novel strategy to prevent neuronal loss during degenerative processes. PMID- 22044736 TI - A prolonged experimental febrile seizure results in motor map reorganization in adulthood. AB - INTRODUCTION: Clinical studies have suggested that children experiencing a febrile seizure (FS) before the age of 1year have persistent deficits, but it is unknown whether these seizures lead to permanent cortical reorganization and alterations in function. A FS on the background of increased genetic seizure susceptibility may also lead to negative long-term consequences. Alterations in neocortical motor map expression provide a measure of neocortical reorganization and have been reported in both adults with frontal lobe epilepsy and following seizure induction in experimental models. The objectives of the present study were to determine whether (1) an infantile FS leads to changes to motor map expression in adulthood; (2) long-term cortical reorganization is a function of the age at FS or genetic seizure susceptibility; and (3) different levels of GABA(A) or glutamate receptor subunits or cation-chloride-co-transporters (CCCs) at the time of FS correlate with alterations to motor map expression. MATERIALS AND METHODS: FSs were induced in postnatal day 10 (P10) or P14 Long-Evans (LE) rats or in P14 seizure-prone FAST rats by the administration of the bacterial endotoxin lipopolysaccharide (LPS) and a subconvulsant dose of kainic acid. Ten weeks later intracortical microstimulation was performed to generate motor maps of forelimb movement representations. Sensorimotor neocortex samples were also dissected from naive P10 FAST and P10 and P14 LE pups for western blotting with antibodies against various GABA(A), NMDA, and AMPA receptor subunits and for CCCs. RESULTS: Adult FAST rats had larger motor maps with lower stimulation thresholds after a FS at P14, while adult LE rats had significantly lower map stimulation thresholds but similar sized maps after a FS at P10 compared to controls. There were no differences in neocortical motor map size or stimulation thresholds in adult LE rats after a FS at P14. Both P10 LE and P14 FAST rats had significantly lower levels of the GABA(A) receptor alpha1 subunit, higher levels of the alpha2 subunit, and a higher NKCC1/KCC2 ratio in the sensorimotor cortex compared with the P14 LE rat. In addition, the P14 FAST rats had lower levels of the GluR2 and NR2A receptor subunits in the sensorimotor cortex compared with the P14 LE rats. CONCLUSIONS: A single infantile FS can have long-term effects on neocortical reorganization in younger individuals and those with underlying seizure susceptibility. These changes may be related to an increased level of excitability in the neocortex of younger or genetically seizure-prone rats, as suggested by immaturity of their GABAergic and CCC systems. Given the high incidence of FSs in children, it will be important to gain a better understanding of how age and genetic seizure predisposition may contribute to the long-term sequelae of these events. PMID- 22044737 TI - Transcriptional changes in adhesion-related genes are site-specific during noise induced cochlear pathogenesis. AB - Cell-cell junctions and junctions between cells and extracellular matrix are essential for maintenance of the structural and functional integrity of the cochlea, and are also a major target of acoustic trauma. While morphological assessments have revealed adhesion dysfunction in noise-traumatized cochleae, the molecular mechanisms responsible for adhesion disruption are not clear. Here, we screened the transcriptional expression of 49 adhesion-related genes in normal rat cochleae and measured the expression changes in the early phases of cochlear pathogenesis after acoustic trauma. We found that genes from four adhesion families, including the immunoglobulin superfamily and the integrin, cadherin, and selectin families, are expressed in the normal cochlea. Exposure to an intense noise at 120dB sound pressure level (SPL) for 2h caused site-specific changes in expression levels in the apical and the basal sections of the sensory epithelium. Expression changes that occurred in the cochlear sensory epithelium were biphasic, with early upregulation at 2h post-noise exposure and subsequent downregulation at 1day post-exposure. Importantly, the altered expression level of seven genes (Sgce, Sell, Itga5, Itgal, Selp, Cntn1 and Col5a1) is related to the level of threshold shift of the auditory brainstem response (ABR), an index reflecting functional change in the cochlea. Notably, the genes showing expression changes exhibited diverse constitutive expression levels and belong to multiple adhesion gene families. The finding of expression changes in multiple families of adhesion genes in a temporal fashion (2h vs. 1day) and a spatial fashion (the apical and the basal sensory epithelia as well as the lateral wall tissue) suggests that acoustic overstimulation provokes a complex response in adhesion genes, which likely involves multiple adhesion-related signaling pathways. PMID- 22044739 TI - Immunogenicity of hepatitis B vaccine among hemodialysis patients: effect of revaccination of non-responders and duration of protection. AB - BACKGROUND: Hepatitis B vaccination is recommended for patients on hemodialysis, however, seroprotection after a primary vaccine series is suboptimum. Limited data are available on the effect of revaccination of non-responders and on persistence of immunity in this population. METHODS: Hepatitis B vaccine (40 MUg/dose) was given to 77 susceptible patients on hemodialysis (0, 1, and 6 month schedule). Levels of hepatitis B surface antibody (anti-HBs) were tested >= 28 days after the third dose was administered, and non-responders revaccinated with an additional 3-dose series. Vaccine responders (anti-HBs >=10 mIU/mL) were re tested every 6 months and booster doses given as needed. Kaplan-Meier survival curve was used to estimate the probability of maintaining protective antibody level. Cox-proportional hazards models were used to assess the association between time to loss of protective antibody levels and certain explanatory variables. RESULTS: Overall primary vaccine-induced response was 79.2% (95% CI 68.2%, 87.3%), including 49/77 (63.6%; 95% CI 51.8%, 74.7%) patients who received the initial primary hepatitis B vaccine series and 12/21 (57.1%; 95% CI 34.4%, 77.4%) non-responders who were revaccinated with an additional series. Among weak responders (anti-HBs level 10.0-99.9 mIU/mL), protective antibody levels persisted in 44% for 12 months post-vaccination; whereas among strong responders (anti-HBs level >=100 mIU/mL), protective antibody levels persisted in 92% for 12 months, and 68% for 24 months post-vaccination. A weak post-vaccination response increased the risk of losing protective antibody levels (adjusted hazard ratio, 9.7; 95% confidence interval, 3.5-28.5; p<0.0001). CONCLUSION: Revaccinating patients undergoing hemodialysis who do not respond to a primary vaccine series substantially increases the pool of protected patients. The threshold for defining hepatitis B vaccine-induced immunity should be revisited in this patient population to maximize the duration of protection. PMID- 22044738 TI - Evaluation of SLOG/TCI-III pediatric system on target control infusion of propofol. AB - BACKGROUND: The target-controlled infusion-III (SLOG/TCI-III) system was derived from a model set up by the local pediatric population for target control infusion of propofol. METHODS: The current study aimed at evaluating the difference between target concentrations of propofol and performance, which was measured using the SLOG/TCI-III system in children. Thirty children fulfilling the I-II criteria according to American Society of Anesthesiology were enrolled in the study. The target plasma concentration of propofol was fed into the SLOG/TCI-III system and compared with the measured concentrations of propofol. Blood samples were collected and analyzed by high performance liquid chromatography with fluorescence detector. The performance error (PE) was determined for each measured blood propofol concentration. The performances of the TCI-III system were determined by the median performance error (MDPE), the median absolute performance error (MDAPE), and Wobble (the median absolute deviation of each PE from the MDPE), respectively. RESULTS: Concentration against target concentration showed good linear correlation: concentration = 1.3428 target concentration - 0.2633 (r = 0.8667). The MDPE and MDAPE of the pediatric system were 10 and 22%, respectively, and the median value for Wobble was 24%. MDPE and MDAPE were less than 15 and 30%, respectively. CONCLUSIONS: The performance of TCI-III system seems to be in the accepted limits for clinical practice in children. PMID- 22044740 TI - Knowledge, attitudes, and beliefs about seasonal influenza and H1N1 vaccinations in a low-income, public health clinic population. AB - OBJECTIVE: The Public Health Center Vaccine Survey (PHCVS) examines the knowledge, attitudes, and beliefs about seasonal influenza and H1N1 vaccinations in a largely low-income, urban, public health clinic population in Los Angeles County, USA. DESIGN: A cross-sectional survey of vulnerable individuals at risk for severe influenza infection was conducted in one of the nation's largest local public health jurisdictions. SUBJECTS: A total of 1541 clinic patients were recruited in the waiting rooms of five large public health centers in Los Angeles County from June to August, 2010. RESULTS: Among prospective respondents who met eligibility criteria, 92% completed the survey. The majority was black or Latino and most were between the ages of 18 and 44 years. More than half were unemployed; two-thirds had no health insurance; and nearly one-half reported having a high school education or less. About one-fifth reported they had received the H1N1 vaccine during the previous flu season. In comparative analyses, negative beliefs about vaccine safety and efficacy were highly predictive of H1N1 vaccination. Blacks were less likely than non-black respondents to report receiving the H1N1 vaccine (OR=0.7, 95% CI=0.6-1.0). Blacks were also less likely than other respondents to agree that vaccines can prevent disease (OR=0.4, 95% CI=0.3-0.5), that vaccines are safe (OR=0.5, 95% CI=0.4 0.6), and that they trust doctors/clinicians who recommend vaccines (OR=0.5, 95% CI=0.4-0.7). CONCLUSIONS: Study findings provide a useful risk profile of vulnerable groups in Los Angeles County, which may be generalizable to other urban jurisdictions in the United States. They also describe real world situations that can be used to forecast potential challenges that vaccine beliefs may pose to national as well as local influenza pandemic planning and response, especially for communities with limited access to these preventive services. PMID- 22044741 TI - Immunological adjuvant efficacy of glycyrrhetinic acid liposome against Newcastle disease vaccine. AB - The aim of this study is to investigate whether the activity of inducing immune response of glycyrrhetinic acid (GA) could be enhanced after GA was encapsulated with liposome. Three hundred and fifty 14-day-old chickens were randomly assigned to 7 groups and vaccinated with Newcastle disease (ND) vaccine. Simultaneously, the chickens in experimental groups were injected with the glycyrrhetinic acid liposome (GAL) at three doses, GA and blank liposome, respectively. The activity of serum antibody titer, concentrations of immunoglobulins G (IgG) and immunoglobulins M (IgM), lymphocytes proliferation, the proportions of lymphocyte subpopulations (CD4(+) and CD8(+)) was determined after vaccination. GAL was evaluated for inducing humoral immunity and cellular immunity in chicken against Newcastle disease (ND) vaccine. The results showed that GAL not only could significantly enhance the antibody titers, IgG and IgM in ND vaccine immunized chicken, but also significantly promote the lymphocyte proliferation and the proportions of CD4(+) and CD8(+), as comparison with GA, BL and VC control groups. Moreover, the effects appear a dose-dependent manner and a time-dependent manner. These indicated that GAL could significantly promote the activation potential of humoral immunity and cellular immunity in chicken and present certain dose-effect and time-effect relationships. The formulations of GA and liposome can further enhance the immune response against ND vaccine compared with the adjuvant alone. PMID- 22044742 TI - Control of methicillin resistant Staphylococcus aureus infection utilizing a novel immunostimulatory peptide. AB - The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a serious health concern worldwide that requires new therapeutic approaches that extend beyond the development and use of new antibiotics. In this study, a conformationally biased, response-selective agonist of human C5a, known as EP67, was used to induce host innate immunity as a therapeutic method of reducing CA-MRSA infections. Using a murine model of dermonecrosis we show that EP67 treatment effectively limits CA-MRSA infection by promoting cytokine synthesis and neutrophil influx. In contrast, EP67 was ineffective in reducing lesion formation in C5a receptor (CD88(-/-)) knockout mice, indicating that EP67 activates host innate immunity by engagement of CD88 bearing cells. These results suggest that EP67 may serve as a novel immunotherapeutic for prevention and treatment of CA-MRSA dermal infection. PMID- 22044743 TI - Comparative analysis of the complete genome sequences of two Australian origin live attenuated vaccines of infectious laryngotracheitis virus. AB - Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that causes acute respiratory disease in poultry. Live attenuated ILTV vaccines have been used extensively to help control outbreaks of disease. Two Australian-origin attenuated vaccine strains, SA2 and A20 ILTV, are commercially available and are in frequent use in Australia. Both these vaccines are of chicken embryo origin (CEO). The A20 ILTV strain was developed from the SA2 ILTV strain by sequential passage of SA2 ILTV in tissue culture in order to reduce its residual virulence. Previous studies in our laboratories have demonstrated the greater attenuation of A20 ILTV under controlled experimental conditions, but the genetic basis of the in vivo phenotypes of A20 and SA2 ILTV has not been elucidated. In this study, the genetic differences between A20 and SA2 ILTV were examined by performing complete genome sequencing and comparative analysis. The genome sequences were also compared to a reference sequence from another CEO ILTV vaccine (Serva ILTV: GenBank accession number HQ_630064) of European-origin. Additional in ovo studies to assess cell to cell spread were performed in order to allow further comparisons of the pathogenicity of SA2 and A20 ILTV. The sequencing results showed that the genome sizes of SA2 and A20 ILTV were 152,975 and 152,978bp, respectively, while Serva ILTV had a genome size of 152,630bp. The genomes of SA2 and A20 ILTV shared 99.9% nucleotide sequence identity with each other, but only 99.2% identity with Serva ILTV. In complete genome alignments between SA2 and A20 ILTV, a total of 24 single nucleotide polymorphisms (SNPs) were identified, but only two of these were non-synonymous. These were located in the ORF B and UL15 genes. Four indels were detected in non-coding regions. The findings from this study demonstrate the general genetic stability of ILTV, but also show that non synonymous changes in the ORF B and UL15 genes have arisen following tissue culture passage of SA2 ILTV to produce the A20 vaccine. It is likely that these non-synonymous changes are related to the greater attenuation of A20 ILTV compared to SA2 ILTV, and to the reduced ability of A20 ILTV to spread from cell to cell, as observed in this study. The results from this study also demonstrate the divergence between the genomes of the Australian-origin ILTV vaccine strains and the Serva vaccine strain. PMID- 22044744 TI - Improving inpatient postnatal services: midwives views and perspectives of engagement in a quality improvement initiative. AB - BACKGROUND: Despite major policy initiatives in the United Kingdom to enhance women's experiences of maternity care, improving in-patient postnatal care remains a low priority, although it is an aspect of care consistently rated as poor by women. As part of a systems and process approach to improving care at one maternity unit in the South of England, the views and perspectives of midwives responsible for implementing change were sought. METHODS: A Continuous Quality Improvement (CQI) approach was adopted to support a systems and process change to in-patient care and care on transfer home in a large district general hospital with around 6000 births a year. The CQI approach included an initial assessment to identify where revisions to routine systems and processes were required, developing, implementing and evaluating revisions to the content and documentation of care in hospital and on transfer home, and training workshops for midwives and other maternity staff responsible for implementing changes. To assess midwifery views of the quality improvement process and their engagement with this, questionnaires were sent to those who had participated at the outset. RESULTS: Questionnaires were received from 68 (46%) of the estimated 149 midwives eligible to complete the questionnaire. All midwives were aware of the revisions introduced, and two-thirds felt these were more appropriate to meet the women's physical and emotional health, information and support needs. Some midwives considered that the introduction of new maternal postnatal records increased their workload, mainly as a consequence of colleagues not completing documentation as required. CONCLUSIONS: This was the first UK study to undertake a review of in-patient postnatal services. Involvement of midwives at the outset was essential to the success of the initiative. Midwives play a lead role in the planning and organisation of in-patient postnatal care and it was important to obtain their feedback on whether revisions were pragmatic and achieved anticipated improvements in care quality. Their initial involvement ensured priority areas for change were identified and implemented. Their subsequent feedback highlighted further important areas to address as part of CQI to ensure best quality care continues to be implemented. Our findings could support other maternity service organisations to optimise in-patient postnatal services. PMID- 22044745 TI - Red blood cell transfusion and increased length of storage are not associated with deep vein thrombosis in medical and surgical critically ill patients: a prospective observational cohort study. AB - INTRODUCTION: With prolonged storage times, cell membranes of red blood cells (RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'. Storage lesions may promote inflammation and thrombophilia when transfused. In trauma patients, RBC transfusion was an independent risk factor for deep vein thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or more units were transfused. The objective of this study was to determine if RBC transfusions or RBC storage age predicts incident DVT in medical or surgical intensive care unit (ICU) patients. METHODS: Using a database which prospectively enrolled 261 patients over the course of 1 year with an ICU stay of at least 3 days, we analyzed DVT and RBC transfusions using Cox proportional hazards regression. Transfusions were analyzed with 4 thresholds, and storage age using 3 thresholds. DVTs were identified by twice-weekly proximal leg ultrasounds. Multivariable analyses were adjusted for 4 significant DVT predictors in this population (venous thrombosis history, chronic dialysis, platelet transfusion and inotropes). RESULTS: Of 261 patients, 126 (48.3%) had at least 1 RBC transfusion; 46.8% of those transfused had >= 5 units in ICU. Patients receiving RBCs were older (68.8 vs 64.1 years), more likely to be female (47.0 vs 30.7), sicker (APACHEII 26.8 vs 24.4), and more likely to be surgical (21.4 vs 8.9) (P < 0.05). The total number of RBCs per patient was 1-64, mean was 6.3 (SD 7.5), median was 4 (IQR 2,8). In univariate analyses, there was no association between DVT and RBC exposure (1 day earlier, 3 days earlier, 7 days earlier, or ever) or RBC storage (<= 7 or > 7 days, <= 14 or > 14 days, <= 21 or > 21 days). Among patients transfused, no multivariable analyses showed that RBC transfusion or storage age predicted DVT. Trends were counter to the hypothesis (e.g., RBC storage for <= 7 days suggested a higher DVT risk compared to > 7 days (HR 5.3; 95% CI 1.3-22.1). CONCLUSIONS: We were unable to detect any association between RBC transfusions or prolonged red cell storage and increased risk of DVT in medical or surgical ICU patients. Alternate explanations include a lack of sufficient events or patients' interaction, between patient groups, a mixing of red cell storage times creating differential effects on DVT risk, and unmeasured confounders. PMID- 22044747 TI - Characteristics of the aberrant pyramidal tract in comparison with the pyramidal tract in the human brain. AB - BACKGROUND: The aberrant pyramidal tract (APT) refers to the collateral pathway of the pyramidal tract (PT) through the medial lemniscus in the midbrain and pons. Using diffusion tensor tractography (DTT), we investigated the characteristics of the APT in comparison with the PT in the normal human brain. RESULTS: In thirty-four (18.3%, right hemisphere: 20, left hemisphere: 14) of the 186 hemispheres, the APTs separated from the PT at the upper midbrain level, descended through the medial lemniscus from the midbrain to the pons, and then rejoined with the PT at the upper medulla. Nine (26.5%) of the 34 APTs were found to originate from the primary somatosensory cortex without a primary motor cortex origin. Values of fractional anisotropy (FA) and tract volume of the APT were lower than those of the PT (P < 0.05); however, no difference in mean diffusivity (MD) value was observed (P > 0.05). CONCLUSION: We found that the APT has different characteristics, including less directionality, fewer neural fibers, and less origin from the primary motor cortex than the PT. PMID- 22044748 TI - Glycolic acid-g-chitosan-gold nanoflower nanocomposite scaffolds for drug delivery and tissue engineering. AB - This paper reports a simple novel method for the synthesis of flower like gold nanoparticle (three dimensional branched nanoparticle) with >30 tips, under controlled temperature condition. Formation of flower like Au nanoparticle was confirmed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Next step of this paper reveals the potential use of novel hybrids of chitosan-g-glycolic acid and gold nanoflower (AuNF) in controlled drug delivery and tissue engineering applications. The drug loaded novel nanohybrid scaffold is prepared by freeze drying of grafted polymer solution. Grafting of glycolic acid to the chitosan and incorporation of drug were evaluated by Fourier transform infrared spectroscopy (FTIR). The nanohybrid scaffolds were found to be stable towards the pH of the medium. The cell viability study shows that prepared nanohybrid scaffolds are biocompatible. Gold nanoflowers were found to control the drug release rate in the buffer solution (pH 7.4). Therefore, for the glycolic acid grafted chitosan based system, gold nanoflowers are the viable additive for drug delivery. PMID- 22044749 TI - Effects of the polysaccharide from Pholiota nameko on human cytokine network in serum. AB - Some physico-chemical characterizations of Pholiota nameko polysaccharides (PNPS 1) were studied, including sulfate content, UV/visible and infrared spectra, also the variation of cytokine communication network in serum to clarify the pharmacological effects of PNPS-1 by determination of 39 cytokines in serum of healthy volunteers. The result proved that PNPS-1 possessed significant anti inflammatory activity. Further, we use Microsoft Visio 2007 software to map out the cell-cell communication network diagram. The analysis to the diagram suggested that PNPS-1 could take effect on the innate and adaptive immunity and hematopoiesis of volunteers. PMID- 22044750 TI - Noncollagenous 16A domain of type XVII collagen-reactive CD4+ T cells play a pivotal role in the development of active disease in experimental bullous pemphigoid model. AB - Bullous pemphigoid (BP), the most common autoimmune blistering disease, is caused by autoantibodies against type XVII collagen (COL17). We recently demonstrated that CD4+ T cells were crucial for the production of anti-COL17 IgG and for the development of the BP phenotype by using a novel active BP mouse model by adoptively transferring immunized splenocytes into immunodeficient COL17 humanized mice. Noncollagenous 16A (NC16A) domain of COL17 is considered to contain the main pathogenic epitopes of BP, however, the pathogenicity of COL17 NC16A-reactive CD4+ T cells has never been elucidated. To address this issue, we modulated the immune responses against COL17 in active BP model by using anti CD40 ligand (CD40L) monoclonal antibody MR1, an inhibitor of the CD40-CD40L interaction, in various ways. First, we show the essential role of CD4+ T cells in the model by showing that CD4+ T cells isolated from wild-type mice immunized with human COL17 enabled naive B cells to produce anti-COL17 NC16A IgG in vivo. Second, we show that the activation of anti-COL17 NC16A IgG-producing B cells via CD40-CD40L interaction was completed within 5 days after the adoptive transfer of immunized splenocytes. Notably, a single administration of MR1 at day 0 was enough to inhibit the production of anti-COL17 NC16A IgG and to diminish skin lesions despite the presence of restored anti-COL17 IgG at the later stage. In contrast, the delayed administration of MR1 failed to inhibit the production of anti-COL17 NC16A IgG and the development of the BP phenotype. These results strongly suggest that COL17 NC16A-reactive CD4+ T cells play a pivotal role in the production of pathogenic autoantibodies and in the development of active disease in experimental BP model. PMID- 22044751 TI - Heritability and genome-wide association analysis of renal sinus fat accumulation in the Framingham Heart Study. AB - BACKGROUND: Ectopic fat accumulation in the renal sinus is associated with chronic kidney disease and hypertension. The genetic contributions to renal sinus fat accumulation in humans have not been well characterized. METHODS: The present analysis consists of participants from the Framingham Offspring and Third Generation who underwent computed tomography; renal sinus fat and visceral adipose tissue (VAT) were quantified. Renal sinus fat was natural log transformed and sex- and cohort-specific residuals were created, adjusted for (1) age, (2) age and body mass index (BMI), and (3) age and VAT. Residuals were pooled and used to calculate heritability using variance-components analysis in SOLAR. A genome-wide association study (GWAS) for renal sinus fat was performed using an additive model with approximately 2.5 million imputed single nucleotide polymorphisms (SNPs). Finally, we identified the associations of renal sinus fat in our GWAS results with validated SNPs for renal function (n=16), BMI (n=32), and waist-to-hip ratio (WHR, n=14), and applied a multi-SNP genetic risk score method to determine if the SNPs for each renal and obesity trait were in aggregate associated with renal sinus fat. RESULTS: The heritability of renal sinus fat was 39% (p<0.0001); results were not materially different after adjustment for BMI (39%) or VAT (40%). No SNPs reached genome-wide significance in our GWAS. In our candidate gene analysis, we observed nominal, direction consistent associations with renal sinus fat for one SNP associated with renal function (p=0.01), two associated with BMI (p<0.03), and two associated with WHR (p<0.03); however, none remained significant after accounting for multiple testing. Finally, we observed that in aggregate, the 32 SNPs associated with BMI were nominally associated with renal sinus fat (multi-SNP genetic risk score p=0.03). CONCLUSIONS: Renal sinus fat is a heritable trait, even after accounting for generalized and abdominal adiposity. This provides support for further research into the genetic determinants of renal sinus fat. While our study was underpowered to detect genome-wide significant loci, our candidate gene BMI risk score results suggest that variability in renal sinus fat may be associated with SNPs previously known to be associated with generalized adiposity. PMID- 22044752 TI - RNA editing sites exist in protein-coding genes in the chloroplast genome of Cycas taitungensis. AB - RNA editing is a post-transcriptional process that results in modifications of ribonucleotides at specific locations. In land plants editing can occur in both mitochondria and chloroplasts and most commonly involves C-to-U changes, especially in seed plants. Using prediction and experimental determination, we investigated RNA editing in 40 protein-coding genes from the chloroplast genome of Cycas taitungensis. A total of 85 editing sites were identified in 25 transcripts. Comparison analysis of the published editotypes of these 25 transcripts in eight species showed that RNA editing events gradually disappear during plant evolution. The editing in the first and third codon position disappeared quicker than that in the second codon position. ndh genes have the highest editing frequency while serine and proline codons were more frequently edited than the codons of other amino acids. These results imply that retained RNA editing sites have imbalanced distribution in genes and most of them may function by changing protein structure or interaction. Mitochondrion protein coding genes have three times the editing sites compared with chloroplast genes of Cycas, most likely due to slower evolution speed. PMID- 22044753 TI - Immunomonitoring results of a phase II/III study of malignant ascites patients treated with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3). AB - Patients with malignant ascites secondary to primary carcinomas benefit from intraperitoneal therapy with the trifunctional antibody catumaxomab (anti-EpCAM * anti-CD3). Here, we report the analysis of peritoneal fluid samples from 258 patients with malignant ascites randomized to catumaxomab or control groups to investigate the molecular effects of catumaxomab treatment. In the catumaxomab group, tumor cell numbers and peritoneal levels of VEGF decreased, whereas the activation status of CD4(+) and CD8(+) T-cell populations increased more than two fold after treatment. Notably, CD133(+)/EpCAM(+) cancer stem cells vanished from the catumaxomab samples but not from the control samples. In vitro investigations indicated that catumaxomab eliminated tumor cells in a manner associated with release of proinflammatory Th1 cytokines. Together, our findings show that catumaxomab therapy activates peritoneal T cells and eliminates EpCAM(+) tumor cells, establishing a molecular and cellular basis to understand in vivo efficacy within the immunosuppressed malignant ascites tissue microenvironment. PMID- 22044754 TI - Evaluation of the efficacy of immunocastration vaccine composed of gonadotrophin releasing hormone conjugated with Salmonella typhimurium flagellin in rats. AB - Immunocastration is an alternative method to replace surgical castration that is commonly performed in domestic and pet animals. In this study, a new immunocastration vaccine was developed, and its efficacy was evaluated in male rats. Six tandem copies of gonadotrophin-releasing hormone (GnRH) peptide were genetically fused to Salmonella typhimurium flagellin fljB (STF2) that is a ligand of toll-like receptor 5 (TLR5). The recombinant STF2-GnRH protein expressed in Escherichia coli was used as the immunocastration vaccine. Sixteen male rats were equally assigned to four groups. Excluding the control rats, three groups were immunized with 100, 200 and 400 MUg of the STF2-GnRH vaccine, respectively. All of the immunized rats developed significantly higher titres of antibodies to GnRH than the control rats. The size and weight of both testes and epididymides from the immunized rats were significantly smaller than those of the control rats. Testicular tissues in the immunized rats demonstrated atrophy of seminiferous tubules and decreased numbers of both spermatogonia and spermatocytes. These data indicate that the newly developed STF2-GnRH vaccine has a potent immunogenicity to GnRH and efficiently suppresses the development of testes in rats. PMID- 22044755 TI - Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features. AB - BACKGROUND: Increased understanding of the variability in normal breast biology will enable us to identify mechanisms of breast cancer initiation and the origin of different subtypes, and to better predict breast cancer risk. METHODS: Gene expression patterns in breast biopsies from 79 healthy women referred to breast diagnostic centers in Norway were explored by unsupervised hierarchical clustering and supervised analyses, such as gene set enrichment analysis and gene ontology analysis and comparison with previously published genelists and independent datasets. RESULTS: Unsupervised hierarchical clustering identified two separate clusters of normal breast tissue based on gene-expression profiling, regardless of clustering algorithm and gene filtering used. Comparison of the expression profile of the two clusters with several published gene lists describing breast cells revealed that the samples in cluster 1 share characteristics with stromal cells and stem cells, and to a certain degree with mesenchymal cells and myoepithelial cells. The samples in cluster 1 also share many features with the newly identified claudin-low breast cancer intrinsic subtype, which also shows characteristics of stromal and stem cells. More women belonging to cluster 1 have a family history of breast cancer and there is a slight overrepresentation of nulliparous women in cluster 1. Similar findings were seen in a separate dataset consisting of histologically normal tissue from both breasts harboring breast cancer and from mammoplasty reductions. CONCLUSION: This is the first study to explore the variability of gene expression patterns in whole biopsies from normal breasts and identified distinct subtypes of normal breast tissue. Further studies are needed to determine the specific cell contribution to the variation in the biology of normal breasts, how the clusters identified relate to breast cancer risk and their possible link to the origin of the different molecular subtypes of breast cancer. PMID- 22044756 TI - BDM1, a phosducin-like gene of Fusarium graminearum, is involved in virulence during infection of wheat and maize. AB - Fusarium graminearum is a common pathogen of wheat and maize throughout the world. Despite recent advances in the elucidation of the genetic basis of virulence, significant gaps in the regulatory network underlying pathogenesis remain to be filled. In particular, little is known at the molecular level about the overlap among mechanisms of pathogenicity on maize and wheat. G-protein signalling has been implicated in pathogenesis in F. graminearum, although the underlying mechanisms are not fully understood. In this study, we investigated the involvement of a putative phosducin-like gene (BDM1) in growth, development and pathogenesis in F. graminearum. Targeted deletion of BDM1 revealed roles in sexual and asexual sporulation, germ tube development, hyphal branching and mycelial morphology. During pathogenesis, BDM1 is required for wild-type levels of colonization of maize silk tissue and stalks, but is dispensable for the colonization of kernels. The deletion of BDM1 also reduced the virulence of F. graminearum during the infection of wheat seedlings and heads, resulting in a significant reduction in fungal biomass and a delayed spread of visual symptom expression (i.e. bleaching in heads). Furthermore, BDM1 is required for wild-type levels of deoxynivalenol biosynthesis during the infection of wheat heads and maize silks. In summation, BDM1 is one of the few genes characterized to date in F. graminearum involved in virulence during infection of both maize and wheat. Thus, the functional characterization of BDM1 has established a new regulatory link between pathogenesis in maize and wheat, and provides a genetic resource through which the regulatory networks underlying virulence in F. graminearum can be further elucidated. PMID- 22044757 TI - Plasma membrane association of three classes of bacterial toxins is mediated by a basic-hydrophobic motif. AB - Plasma membrane targeting is essential for the proper function of many bacterial toxins. A conserved fourhelical bundle membrane localization domain (4HBM) was recently identified within three diverse families of toxins: clostridial glucosylating toxins, MARTX toxins and Pasteurella multocida-like toxins. When expressed in tissue culture cells or in yeast, GFP fusions to at least one 4HBM from each toxin family show significant peripheral membrane localization but with differing profiles. Both in vivo expression and in vitro binding studies reveal that the ability of these domains to localize to the plasma membrane and bind negatively charged phospholipids requires a basic-hydrophobic motif formed by the L1 and L3 loops. The different binding capacity of each 4HBM is defined by the hydrophobicity of an exposed residue within the motif. This study establishes that bacterial effectors utilize a normal host cell mechanism to locate the plasma membrane where they can then access their intracellular targets. PMID- 22044758 TI - Mandibular flexure and its significance on implant fixed prostheses: a review. AB - PURPOSE: The aims of this review are to determine the effect of mandibular flexure on the "implant-framework system," and analyze the existing literature on the topic. MATERIALS AND METHODS: A MEDLINE and PubMed search was conducted to identify any articles in English related to the topic published up to May 2010 using the search words "mandible,""dental implants,""dental impression technique,""jaw movement,""dental stress analysis," and "mechanical stress." RESULTS: The search identified 40 and 36 articles from MEDLINE and PubMed, respectively. Twenty articles met the inclusion criteria. CONCLUSIONS: Mandibular flexure is a multifactorial phenomenon, and the effect of the implant-framework system in this is unclear. Studies have focused mainly on the fully edentulous mandible. These have found that mandibular flexure should be taken into consideration when designing a prosthesis and have suggested that dividing the prosthesis at the symphysis region, or into multiple implant fixed dental prostheses, may minimize the effect of mandibular flexure on the implant prosthesis. At this time, no studies have investigated the effect of mandibular flexure on long-span, unilateral, implant fixed prostheses. The clinical significance of mandibular flexure on the success of dental implant treatment is at this time unclear, and further research is needed. PMID- 22044759 TI - Current trends in the diagnosis and treatment of autoimmune hepatitis in Japan. AB - While a certain international consensus has been reached regarding the diagnosis and treatment of autoimmune hepatitis (AIH), there are some unique clinical characteristics of AIH in Japan. For diagnosis of AIH using the new simplified criteria proposed by the International Autoimmune Hepatitis Group, it is necessary to re-evaluate the antibody titer determined by using HEp-2 cells, which are widely used in Japan, and the finding of emperipolesis in liver histology, although the criteria are useful for rapid identification of AIH in routine clinical practice. The use of azathioprine as first-line therapy for AIH is limited in Japan because the drug is not covered by the Japanese national health insurance. Concomitant use of ursodeoxycholic acid (UDCA) to reduce corticosteroids and use of UDCA as monotherapy are therefore considered promising. Moreover, a relatively good survival rate has been reported in patients who developed AIH-induced acute liver failure and underwent living-donor liver transplantation. Current trends in the diagnosis and treatment of AIH in Japan are described in this report with a review of recent findings. PMID- 22044760 TI - CD68 and CD163 as prognostic factors for Korean patients with Hodgkin lymphoma. AB - BACKGROUND: Limited progress had been made in prognostic stratification of patients with Hodgkin lymphoma (HL) until recent studies suggested that the number of CD68-expressing macrophages is prognostic in classical HL. However, its significance in Asian patients with HL has not been explored yet perhaps because of its low incidence in Asia. METHODS: In this work, we performed immunohistochemical analysis of CD163, as well as CD68, in 144 Korean patients with HL treated between November 1990 and December 2009 in a single center. The relative percentages of CD68+ and CD163+ cells with respect to the overall cellularity (CD68 index and CD163 index, respectively) were correlated with clinical outcomes. RESULTS: Both high CD68 and CD163 indices (>20%) were associated with a rise in treatment-related deaths and poorer event-free survival (P = 0.009 and P = 0.0023, respectively), disease-specific survival (P = 0.011 and P = 0.001), and overall survival (P = 0.023 and P = 0.001). In particular, a high CD163 index was related to lower complete response (CR) rate (P = 0.022) and shorter duration of CR (P = 0.030). CONCLUSIONS: High index of either CD68 or CD163 (>20%) is significantly correlated with poor prognosis in Korean patients with HL. CD163, a specific marker of macrophages, seems to be another prognostic factor for classical HL. PMID- 22044761 TI - Does haemophilia protect against ischaemic cardiovascular disease? PMID- 22044762 TI - Transforming care at the bedside for nurse faculty: can continuous quality improvement transform nursing education? PMID- 22044764 TI - Evidence for behavioral benefits of early dietary supplementation with CoEnzymeQ10 in a slowly progressing mouse model of Huntington's disease. AB - Controversies surround the usefulness of Coenzyme Q10 (CoQ10) in Huntington's disease (HD), an autosomal dominant, fatal, neurodegenerative disease with no cure or disease modifying treatment. CoQ10, an endogenous substrate for electron transport and an anti-oxidant, has been shown in some but not all studies to improve symptoms and survival in mouse models of HD. Previous studies have been conducted in fast-progressing models that better mimic the juvenile forms of HD than the much more common middle-age onset form, possibly accounting for mixed results. Establishing the usefulness of CoQ10 to alter HD disease course in a model that better recapitulates the progressive features of the human disorder is important because clinical trials of CoQ10, which is safe and well tolerated, are being planned in patients. The CAG140 knock-in (KI) mouse model of HD in which an expanded (approximately 120) CAG repeat is inserted in the mouse gene provides a model of the mutation in the proper genomic and protein context. These mice display progressive motor, cognitive and emotional anomalies, transcriptional disturbances and late striatal degeneration. Homozygote mutant CAG140 KI mice and wild-type littermates were fed CoQ10 (0.2%, 0.6%) in chow, and behavioral and pathological markers of disease were examined. CoQ10 improved early behavioral deficits and normalized some transcriptional deficits without altering huntingtin aggregates in striatum. The lower dose (0.2%) was more beneficial than 0.6%. Similar to previous studies, this low dose also induced deleterious effects in open field and rotarod in WT mice, however these effects are of unclear clinical significance in view of the excellent safety profile of CoQ10 in humans. These data confirm that CoQ10 may be beneficial in HD but suggest that maximum benefit may be observed when treatment is begun at early stages of the disease and that dosage may be critical. PMID- 22044766 TI - Diagnostic utility and clinical usefulness of the pocket echocardiographic device. AB - BACKGROUND: The pocket echocardiograph (PE) with color Doppler imaging belongs to a new class of diagnostic tools, the feasibility and accuracy of which is not well established. The aim of this study was to assess the feasibility and diagnostic value of transthoracic echocardiography (TTE) performed with the use of PE by a cardiology resident (2nd year of training) and by an experienced cardiologist. METHODS: The study population comprised 220 consecutive patients (142 men, mean age 63 +/- 8 years), 110 of whom were admitted to our intensive cardiac care unit (ICU) and 110 patients referred for TTE from the outpatient clinic. All patients had PE TTE performed by a resident (60 ICU patients, 60 outpatients) or a cardiologist (50 ICU patients, 50 outpatients). Within 24 h of PE TTE, all subjects had a standard TTE (sTTE) performed by an experienced echocardiographer. RESULTS: 96% of patients had echocardiographic measurements completed by both PE TTE and sTTE. The dimensions measured with PE TTE by the resident and the cardiologist showed good to excellent correlation with sTTE (r = 0.64-0.96, P < 0.001). The agreement in detection of various pathologies between PE TTE performed by the resident and sTTE examinations was moderate to very good, whereas it was good to excellent if PE TTE was performed by the experienced cardiologist. CONCLUSION: The diagnostic accuracy of the PE in basic assessment of cardiac morphology and function as compared to standard echocardiography is moderate to very good for a cardiology resident and good to excellent for an experienced cardiologist. (Echocardiography 2012;29:1-6). PMID- 22044765 TI - Rbfox proteins regulate alternative splicing of neuronal sodium channel SCN8A. AB - The SCN8A gene encodes the voltage-gated sodium channel Na(v)1.6, a major channel in neurons of the CNS and PNS. SCN8A contains two alternative exons,18N and 18A, that exhibit tissue specific splicing. In brain, the major SCN8A transcript contains exon 18A and encodes the full-length sodium channel. In other tissues, the major transcript contains exon 18N and encodes a truncated protein, due to the presence of an in-frame stop codon. Selection of exon 18A is therefore essential for generation of a functional channel protein, but the proteins involved in this selection have not been identified. Using a 2.6 kb Scn8a minigene containing exons 18N and 18A, we demonstrate that co-transfection with Fox-1 or Fox-2 initiates inclusion of exon 18A. This effect is dependent on the consensus Fox binding site located 28 bp downstream of exon 18A. We examined the alternative splicing of human SCN8A and found that the postnatal switch to exon 18A is completed later than 10 months of age. In purified cell populations, transcripts containing exon 18A predominate in neurons but are not present in oligodendrocytes or astrocytes. Transcripts containing exon 18N appear to be degraded by nonsense-mediated decay in HEK cells. Our data indicate that RBFOX proteins contribute to the cell-specific expression of Na(v)1.6 channels in mature neurons. PMID- 22044767 TI - The development of service users in the provision of verbal feedback to student nurses in a clinical simulation environment. AB - The School of Nursing and Midwifery at Robert Gordon University, Aberdeen, has a sustained history of working in partnership with service users in their role as patient volunteers. The patient volunteers make a pivotal contribution towards the delivery of clinical skills as "real" patients. They work within a scenario context, overseen and facilitated by academic staff. Evaluations have identified that the patient volunteers find this experience rewarding, worthwhile and a way of contributing to the education of student nurses. Whilst this is already a successful element of the student's learning, staff were cognisant of the need to develop this aspect further. A case study approach was adopted to review the experience of the patient volunteers in their provision of feedback to students. In accordance with the evidence base, it was proposed to enhance the volunteer patient's role in providing verbal face to face feedback to students. An educational package for the patient volunteers was developed and a current simulation event within the curriculum was identified that would allow the volunteers to practice giving feedback. This was then evaluated and following ethical approval, a series of focus groups were undertaken with the patient volunteers. The data collected identified the strengths and limitations of this experience and as a result of this an implementation plan was identified aimed at enhancing the patient volunteer's and the student's experience. PMID- 22044768 TI - Repeated exposure of adult rats to Aroclor 1254 induces neuronal injury and impairs the neurochemical manifestations of the NMDA receptor-mediated intracellular signaling in the hippocampus. AB - Aroclor 1254 is a mixture of polychlorinated biphenyls (PCBs), a class of environmental toxins which cause a wide spectrum of neurotoxic effects. Learning and memory deficits are the profound effects of PCBs which may be related to hippocampal dysfunction. To get insight into the underlying neurochemical mechanisms, we employed the microdialysis technique to investigate the effect of repeated exposure of adult male Wistar rats to Aroclor 1254 (10mg/kg b.w., daily, ig., for 14days), on the neurochemical parameters of NMDA receptor-mediated glutamatergic signaling in the hippocampus in vivo assessed using the microdialysis technique. The results demonstrated that exposure to Aroclor 1254, which was associated with substantial neuronal damage and loss in the hippocampus, markedly decreased the NMDA-induced extracellular accumulation of newly loaded (45)CaCl(2), cGMP and glutamate, and reduced the basal content of the NO precursor, arginine, indicating inhibition of the NMDA/NO/cGMP pathway. Aroclor 1254 exposure also decreased the basal microdialysate content of glutamate and glutamine, which may cause inadequate supply of the neurotransmitter glutamate, while the level of two other neuroactive amino acids, aspartate or taurine was not affected by the exposure. The results underscore neuronal lesion and inhibition of NMDA receptor-mediated glutamatergic signaling in hippocampus as a potential major contributor to the cognitive deficits associated with exposure to PCB. PMID- 22044769 TI - Expression, purification of herpes simplex virus type 1 US11 protein, and production of US11 polyclonal antibody. AB - BACKGROUND: The US11 protein of herpes simplex virus type 1 (HSV-1) is a small, highly basic phosphoprotein expressed at late times during infection. To date, the function of US11 protein in cell culture and animal models is poorly understood. To further investigate the function of the US11 protein, this study was undertaken to express the US11 protein and raise a polyclonal antibody. RESULTS: The US11 gene was cloned into the prokaryotic expression vector pET-32a (+) to express His-tagged US11 protein in Escherichia coli. After purification by nickel affinity chromatography and refolding, the recombinant protein was used to raise the anti-US11 polyclonal antibody. Western blot analysis demonstrated that the US11 protein was specifically recognized by the polyclonal antibody, and immunofluorescent assay also showed that the antibody was able to probe the US11 protein in the cells infected with HSV-1. CONCLUSIONS: In the present study, we obtained a high-level expression of the recombinant US11 protein as well as high titers of rabbit polyclonal antibody specially against US11 protein in HSV-1 infected cells. This special polyclonal antibody provides a good tool for further studying structural and functional characterization of HSV-1 US11 protein. PMID- 22044770 TI - Secondhand smoke exposure induces Raf/ERK/MAPK-mediated upregulation of cerebrovascular endothelin ETA receptors. AB - BACKGROUND: Cigarette smoking enhances the risk of stroke. However, the underlying molecular mechanisms are largely unknown. The present study established an in vivo rat secondhand cigarette smoking (SHS) model and examined the hypothesis that SHS upregulates endothelin receptors with increased cerebrovascular contraction via the Raf/extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinases (MAPK) pathway. RESULTS: Rats were exposed to SHS for up to 8 weeks. The cerebral artery vasoconstriction was recorded by a sensitive myograph. The mRNA and protein expressions for endothelin receptors in cerebral arteries were studied by real-time PCR and Western blot. Compared to fresh air exposed rats, cerebral arteries from SHS rats exhibited stronger contractile responses (P < 0.05) mediated by endothelin type A (ETA) receptors. The expressions of mRNA and protein for ETA receptors in the cerebral arteries from SHS rats were higher (P < 0.05) than that in control. SHS did not affect endothelin type B (ETB) receptor-mediated contractions, mRNA or protein levels. The results suggest that SHS upregulates ETA, but not ETB receptors in vivo. After SHS exposure, the mRNA levels of Raf-1 and ERK1/2, the protein expression of phosphorylated (p)-Raf-1 and p-ERK1/2 were increased (P < 0.05). Raf-1 inhibitor, GW5074 suppressed the enhanced ETA receptor-mediated contraction, mRNA and protein levels induced by SHS. In addition, GW5074 inhibited the SHS-caused increased mRNA and phosphorylated protein levels of Raf 1 and ERK1/2, suggesting that SHS induces activation of the Raf/ERK/MAPK pathway. CONCLUSIONS: SHS upregulates cerebrovascular ETA receptors via the Raf/ERK/MAPK pathway, which provides novel understanding of mechanisms involved in SHS associated stroke. PMID- 22044771 TI - Simultaneous cell growth and ethanol production from cellulose by an engineered yeast consortium displaying a functional mini-cellulosome. AB - BACKGROUND: The recalcitrant nature of cellulosic materials and the high cost of enzymes required for efficient hydrolysis are the major impeding steps to their practical usage for ethanol production. Ideally, a recombinant microorganism, possessing the capability to utilize cellulose for simultaneous growth and ethanol production, is of great interest. We have reported recently the use of a yeast consortium for the functional presentation of a mini-cellulosome structure onto the yeast surface by exploiting the specific interaction of different cohesin-dockerin pairs. In this study, we engineered a yeast consortium capable of displaying a functional mini-cellulosome for the simultaneous growth and ethanol production on phosphoric acid swollen cellulose (PASC). RESULTS: A yeast consortium composed of four different populations was engineered to display a functional mini-cellulosome containing an endoglucanase, an exoglucanase and a beta-glucosidase. The resulting consortium was demonstrated to utilize PASC for growth and ethanol production. The final ethanol production of 1.25 g/L corresponded to 87% of the theoretical value and was 3-fold higher than a similar yeast consortium secreting only the three cellulases. Quantitative PCR was used to enumerate the dynamics of each individual yeast population for the two consortia. Results indicated that the slight difference in cell growth cannot explain the 3-fold increase in PASC hydrolysis and ethanol production. Instead, the substantial increase in ethanol production is consistent with the reported synergistic effect on cellulose hydrolysis using the displayed mini-cellulosome. CONCLUSIONS: This report represents a significant step towards the goal of cellulosic ethanol production. This engineered yeast consortium displaying a functional mini-cellulosome demonstrated not only the ability to grow on the released sugars from PASC but also a 3-fold higher ethanol production than a similar yeast consortium secreting only the three cellulases. The use of more complex cellulosomal structures may further improve the overall efficiency for ethanol production. PMID- 22044772 TI - Non-invasive assessment of liver fibrosis in patients after the Fontan operation. AB - BACKGROUND: This study analyzed the change in liver fibrosis markers after the Fontan operation and investigated their clinical usefulness as an index of congestive liver fibrosis. METHODS: The study enrolled 24 patients who underwent the Fontan operation between January 1994 and December 2008. We subdivided the postoperative period into four intervals and then compared the hepatological markers during each. Eighteen patients underwent postoperative cardiac catheterization and the correlation between hepatological markers and the inferior vena cava (IVC) pressure was analyzed. RESULTS: The mean age of the patients was 138.6 months and the mean interval between the Fontan operation and the examination was 97.8 months. Type IV collagen was extremely high in every interval (I, 286 +/- 93; II, 265 +/- 93; III, 305 +/- 143; IV, 206 +/- 70), while none of the laboratory variables changed significantly in each interval. A significant positive correlation was observed between type IV collagen and the IVC pressure, but no significant correlation with any other hepatological marker was detected. CONCLUSIONS: No specific parameter that reflects the progress in liver fibrosis was identified in this study. The possibility exists that type IV collagen reflects the degree of hepatic congestion. PMID- 22044773 TI - Polymerization profile analysis of resin composite dental restorative materials in real time. AB - OBJECTIVES: In this study, the hypothesis that the polymerization shrinkage profile of "low shrinkage" non-methacrylate based composite; Silorane and "low shrinkage" high molecular mass methacrylate based composite; Kalore is not different from that of three conventional methacrylate based composites (Gradia Direct X, Filtek Supreme XT and Beautifil II) was tested. METHODS: Five commercially available composites were analysed: one "low shrinkage" non methacrylate based composite (Silorane); one "low shrinkage" high molecular mass methacrylate based composite (Kalore) and three conventional methacrylate based composites (Gradia Direct X, Filtek Supreme XT and Beautifil II). Polymerization shrinkage was measured using an electromagnetic balance which recorded changes in composite buoyancy occurring due to volumetric changes during polymerization. This instrument allowed real time volumetric shrinkage measurements to be made at 40 ms intervals. RESULTS: All five resin composites demonstrated a similar volumetric shrinkage profile during polymerization. The rate of shrinkage of all five composites decreased from t=0 at a rate approximating x=t. After 170 s the rate of shrinkage of all five composites was at or below 0.01%/s. During the initial 5s of light exposure Silorane and Kalore exhibited a significantly lower (p<0.05) rate of contraction relative to the three conventional methacrylate composites. After 640 s of analysis, Silorane exhibited a significantly lower (p<0.05) percentage volumetric contraction compared to the other four analysed materials. CONCLUSIONS: The newly developed "low shrinkage" composites (Silorane, Kalore) in the present study demonstrated significantly lower (p<0.05) shrinkage rates and shrinkage volumes compared to the three conventional methacrylate composites. Investigation to identify whether polymerization shrinkage profile analysis is a good predictor of relative polymerization contraction stress levels generated by different composites, is warranted. CLINICAL SIGNIFICANCE: Clinicians making a resin composite selection with the view to minimizing the clinical effects of polymerization shrinkage must consider the rate of polymerization as well as the total volumetric shrinkage of a composite. Silorane (non methacrylate composite) and Kalore (high molecular mass methacrylate composite) have the ability to exhibit lower shrinkage rates and lower shrinkage volumes compared to conventional methacrylate composites. PMID- 22044774 TI - Colour stability of relined dentures after chemical disinfection. A randomised clinical trial. AB - BACKGROUND: This randomised clinical study evaluated the effect of chemical disinfection with sodium perborate or chlorhexidine on the colour stability of a hard chairside reline resin during six months. METHODS: Hard chairside reline resin (Tokuyama Rebase Fast II) was used to reline complete dentures. After baseline colour measurements, the patients were randomly divided into 3 groups (n = 15) and allocation was concealed with the use of the BioStat program. The dentures were cleansed according to three methods: CG (control group)--brushing with coconut soap and soft toothbrush, PG (Perborate group)--brushing according to previous methods and disinfection with warmed sodium perborate solution (Corega Tabs) for 5 min, once a day for 6 months and ChxG (Chlorhexidine Group)- brushing according to CG and disinfection with chlorhexidine digluconate 2% for 5min once a day for 6 months. The data of DeltaE*, DeltaL*, Deltaa* and Deltab* were analysed by 2-way repeated-measures ANOVAs and Tukey tests (alpha = 0.05). RESULTS: There were significant differences amongst groups for DeltaL, Deltaa and Deltab. The time had a significant effect on DeltaE and DeltaL, for all groups evaluated. CONCLUSION: Changes in some colour parameters (DeltaL, Deltaa and Deltab) of the reline resin Tokuyama Rebase were observed when the dentures were disinfected by perborate and chlorhexidine digluconate 2% solutions. The colour stability of was also influenced by time, regardless of disinfection or nondisinfection. CLINICAL IMPLICATIONS: Colour stability of the denture materials is one variable to be considered when choosing disinfection methods. The data in this study will be useful to clinicians when they are selecting disinfectant solutions for disinfection of relined denture. PMID- 22044775 TI - Results of combined treatment of anaplastic thyroid carcinoma (ATC). AB - BACKGROUND: Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies. It is associated with a high rate of local recurrence and with poor prognosis. METHODS: We retrospectively reviewed 44 consecutive patients treated between 1996 and 2010 at Leon Berard Cancer Centre, Lyon, France. The combined treatment strategy derived from the one developed at the Institut Gustave Roussy included total thyroidectomy and cervical lymph-node dissection, when feasible, combined with 2 cycles of doxorubicin (60 mg/m2) and cisplatin (100 mg/m2) Q3W, hyperfractionated (1.2 Gy twice daily) radiation to the neck and upper mediastinum (46-50 Gy), and then four cycles of doxorubicin-cisplatin. RESULTS: Thirty-five patients received the three-phase combined treatment. Complete response after treatment was achieved in 14/44 patients (31.8%). Eight patients had a partial response (18.2%). Twenty-two (50%) had progressive disease. All patients with metastases at diagnosis died shortly afterwards. Thirteen patients are still alive. The median survival of the entire population was 8 months. CONCLUSION: Despite the ultimately dismal prognosis of ATC, multimodality treatment significantly improves local control and appears to afford long-term survival in some patients. There is active ongoing research, and results obtained with new targeted systemic treatment appear encouraging. PMID- 22044776 TI - Efficient and selective removal of chloroacetyl group promoted with tetra-n butylammonium fluoride (TBAF). AB - A practical method for the efficient and selective cleavage of chloroacetyl protecting group using tetra-n-butylammonium fluoride (TBAF) in THF solution at rt was disclosed. PMID- 22044777 TI - Mental illness related disparities in diabetes prevalence, quality of care and outcomes: a population-based longitudinal study. AB - BACKGROUND: Health care disparity is a public health challenge. We compared the prevalence of diabetes, quality of care and outcomes between mental health clients (MHCs) and non-MHCs. METHODS: This was a population-based longitudinal study of 139,208 MHCs and 294,180 matched non-MHCs in Western Australia (WA) from 1990 to 2006, using linked data of mental health registry, electoral roll registrations, hospital admissions, emergency department attendances, deaths, and Medicare and pharmaceutical benefits claims. Diabetes was identified from hospital diagnoses, prescriptions and diabetes-specific primary care claims (17,045 MHCs, 26,626 non-MHCs). Both univariate and multivariate analyses adjusted for socio-demographic factors and case mix were performed to compare the outcome measures among MHCs, category of mental disorders and non-MHCs. RESULTS: The prevalence of diabetes was significantly higher in MHCs than in non-MHCs (crude age-sex-standardised point-prevalence of diabetes on 30 June 2006 in those aged >=20 years, 9.3% vs 6.1%, respectively, P < 0.001; adjusted odds ratio (OR) 1.40, 95% CI 1.36 to 1.43). Receipt of recommended pathology tests (HbA1c, microalbuminuria, blood lipids) was suboptimal in both groups, but was lower in MHCs (for all tests combined; adjusted OR 0.81, 95% CI 0.78 to 0.85, at one year; and adjusted rate ratio (RR) 0.86, 95% CI 0.84 to 0.88, during the study period). MHCs also had increased risks of hospitalisation for diabetes complications (adjusted RR 1.20, 95% CI 1.17 to 1.24), diabetes-related mortality (1.43, 1.35 to 1.52) and all-cause mortality (1.47, 1.42 to 1.53). The disparities were most marked for alcohol/drug disorders, schizophrenia, affective disorders, other psychoses and personality disorders. CONCLUSIONS: MHCs warrant special attention for primary and secondary prevention of diabetes, especially at the primary care level. PMID- 22044778 TI - Characterization of three homoeologous cDNAs encoding chloroplast-targeted aminolevulinic acid dehydratase in common wheat. AB - In the tetrapyrrole biosynthetic pathway of higher plants, 5-aminolevulinic acid (ALA) is metabolized by ALA dehydratase (ALAD). Here, we isolated ALAD1 cDNA from common wheat (Triticum aestivum L.) and its diploid progenitors, and produced transgenic tobacco plants expressing the wheat ALAD1 gene. The ALAD1 genes were highly conserved among wheat relatives, and three homoeologous loci of wheat ALAD1 (TaALAD1) were equally transcribed in common wheat. A transient expression assay of a TaALAD1-GFP (green fluorescent protein) fusion protein suggested that TaALAD1 is localized in chloroplasts. Overexpression of TaALAD1 in transgenic tobacco resulted in a significant increase in ALAD activity in leaves. Moreover, the transgenic tobacco showed vigorous growth and increased survival rate on medium containing ALA at herbicidal concentrations. These results indicate that wheat ALAD1 has catalytic activity in metabolizing ALA in plastids, and that ectopic expression of TaALAD1 in transgenic plants increases their tolerance to ALA application at high concentrations. PMID- 22044779 TI - Family physician attitudes in managing obesity: a cross-sectional survey study. AB - BACKGROUND: Obesity is epidemic in primary care. While family physicians care for the consequences of obesity, they do not generally feel confident managing obesity itself. We examined the barriers to obesity management in a sample of family physicians in a primary care practice-based research network (PBRN). FINDINGS: 204 family physicians were invited to respond to a survey on physician beliefs about obese patients and causes of obesity. A total of 75 physicians responded to the survey. Responses were factor analyzed using standard techniques. Comments were sorted into ranked themes by the investigators. The results show systemic barriers to obesity management. Seven general factors were identified, with some discrepancy seen in the role of "psychobehavioral causation" between rural and non-rural physicians. Themes derived from the comments reflected frustration with the resources and structure of current primary care systems to be able to deal with obesity. CONCLUSIONS: Our pilot survey suggests that differences in beliefs regarding the causes of obesity may exist between rural and non-rural physicians. Further research in larger, more diverse samples is necessary to further illuminate practice differences. More comprehensive approaches to obesity management, like the Chronic Care Model, are suggested by these results. PMID- 22044780 TI - Subversion of innate immune responses by bacterial hindrance of NF-kappaB pathway. AB - Bacterial infections cause substantial mortality and burden of disease globally. Induction of a strong innate inflammatory response is the first common host mechanism required for elimination of the invading pathogens. The host transcription factor, nuclear factor kappa B (NF-kappaB) is essential for immune activation. Conversely, bacterial pathogens have evolved strategies to interfere directly with host cell signalling by regulating or mimicking host proteins. Given the key role of NF-kappaB in the host inflammatory response, bacteria have expectedly developed virulence effectors interfering with NF-kappaB signalling pathways. In this review, we explore the bacterial mechanisms utilized to prevent effective NF-kappaB signalling, which in turn usurp the host inflammatory response. PMID- 22044781 TI - Impact of heteroresistance to colistin in meningitis caused by Acinetobacter baumannii. PMID- 22044782 TI - Acute appendicitis, a rare complication of varicella: a report of three cases. AB - Acute appendicitis is a very rare complication of varicella, and is rarely reported in studies of complications of varicella or appendicitis. This report describes three cases of acute appendicitis in the course of varicella, diagnosed in Clinical Department of Infectious Diseases at Split University Hospital, Croatia between 1998 and 2010. Varicella was diagnosed clinically, and in two cases confirmed by positive serological tests for varicella-zoster virus (VZV). In addition to routine histopathological examination, testing for viral antigens or DNA in the appendix, omentum and peripheral blood by genetic and immunohistochemistry methods may be important to confirm whether VZV and appendicitis are etiopathogenetically connected. PMID- 22044783 TI - effect of embryonic genotype on reference gene selection for RT-qPCR normalization. AB - To obtain more reliable results with biological significance, it requires data normalization using an appropriate internal control gene. In rabbits, there are classic stable reference genes that have been identified for normalization in oocytes and pre-implantation stage embryos. However, effects of embryonic genotype on reference gene selection have not been elucidated. The aim of this study was to test (i) the stability of mRNA transcription level for histone (H2afz) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) genes in rabbit blastocysts from two lines selected by different criteria (litter size and post weaning daily weight gain) and (ii) its influence on biological significance examined by means of a set of embryonic transcripts, such as POU5F1 (Oct-4), epidermal growth factor receptor (erbB3), transforming growth factor-beta2, vascular endothelial growth factor and gamma interferon (Ifn-gamma). The geNorm, NormFinder and BestKeeper programs showed similar results, pointing out that H2afz and GAPDH were the most stable reference genes in rabbits selected on litter size at weaning. Moreover, our study revealed that embryonic genotype affected target gene expression when a single reference gene was used to analyse mRNA expression in blastocysts. Results showed that GAPDH gene is better than H2afz for gene expression studies of both embryo genotypes. A normalization factor derived from H2afz and GAPDH is likely to be appropriate when RT-qPCR was performed in rabbit embryos with different genotypes. PMID- 22044784 TI - Sewer pipe, wire, epoxy, and finger tapping: the start of fMRI at the Medical College of Wisconsin. AB - In 1991, the Biophysics Research Institute at the Medical College of Wisconsin was among the first groups to develop functional Magnetic Resonance Imaging (fMRI). Our story is unique on a few levels: We didn't have knowledge of the ability to image human brain activation with MRI using blood oxygenation dependent (BOLD) contrast until early August of 1991 when we attended the Society for Magnetic Resonance in Medicine (SMRM) meeting in San Francisco, yet we produced our first BOLD-based maps of motor cortex activation about a month later. The effort started with two graduate students, Eric Wong and myself. Only a few days prior to that extremely important SMRM meeting, we had developed human echo planar imaging (EPI) capability in-house. Wong designed, built, and interfaced a head gradient coil made out of sewer pipe, wire, and epoxy to a standard GE 1.5T MRI scanner. Also, a few months prior to building this human head gradient coil he developed the EPI pulse sequences and image reconstruction. All of these efforts were towards a different goal--for demonstration of Wong's novel approach to perfusion imaging in the human brain. Following SMRM, where a plenary lecture by Tom Brady from MGH opened our eyes to human brain activation imaging using BOLD contrast, and where we learned that EPI was extremely helpful if not critical to its success, we worked quickly to achieve our first results on September 14, 1991. The story is also unique in that Jim Hyde had set up the Biophysics Research Institute to be optimal for just this type of rapidly advancing basic technology research. It was well equipped for hardware development, had open and dynamic collaborative relationships with other departments, hospitals on campus, and GE, and had a relatively flat hierarchy and relaxed, flexible, collegial atmosphere internally. Since these first brain activation results, MCW Biophysics has continued to be at the forefront of functional MRI innovation, having helped to pioneer real time fMRI, high resolution fMRI, and functional connectivity mapping. PMID- 22044785 TI - Secretomics identifies Fusarium graminearum proteins involved in the interaction with barley and wheat. AB - Fusarium graminearum is a phytopathogenic fungus primarily infecting small grain cereals, including barley and wheat. Secreted enzymes play important roles in the pathogenicity of many fungi. In order to access the secretome of F. graminearum, the fungus was grown in liquid culture with barley or wheat flour as the sole nutrient source to mimic the host-pathogen interaction. A gel-based proteomics approach was employed to identify the proteins secreted into the culture medium. Sixty-nine unique fungal proteins were identified in 154 protein spots, including enzymes involved in the degradation of cell walls, starch and proteins. Of these proteins, 35% had not been identified in previous in planta or in vitro studies, 70% were predicted to contain signal peptides and a further 16% may be secreted in a nonclassical manner. Proteins identified in the 72 spots showing differential appearance between wheat and barley flour medium were mainly involved in fungal cell wall remodelling and the degradation of plant cell walls, starch and proteins. The in planta expression of corresponding F. graminearum genes was confirmed by quantitative reverse transcriptase-polymerase chain reaction in barley and wheat spikelets harvested at 2-6 days after inoculation. In addition, a clear difference in the accumulation of fungal biomass and the extent of fungal-induced proteolysis of plant beta-amylase was observed in barley and wheat. The present study considerably expands the current database of F. graminearum secreted proteins which may be involved in Fusarium head blight. PMID- 22044786 TI - 5-fluorouracil arterial infusion + interferon therapy for highly advanced hepatocellular carcinoma: A multicenter, randomized, phase II study. AB - AIM: The efficacy and safety of 5-fluorouracil arterial infusion + interferon therapy (FAIT) was evaluated in patients with hepatocellular carcinoma (HCC) with a high degree of vascular invasion associated with poor prognosis, using best salvage therapy (BST) as a reference group. METHODS: Sixty-nine patients with advanced HCC with a high degree of vascular invasion (Vp3, Vp4, Vv3) were randomly assigned to a FAIT group or a BST group. The FAIT group received interferon-alpha and 5-fluorouracil combination therapy; the BST group received either combination therapy of cisplatin and 5-fluorouracil (low-dose FP therapy) or cisplatin for arterial infusion. RESULTS: Thirty patients in the FAIT group and 31 patients in the BST group were included in the efficacy analysis. The response rate (primary endpoint) was 26.7% (eight out of 30 patients) for the FAIT group and 25.8% (eight out of 31) for the BST group. The number of occurrences of adverse events of grade 3 or higher was 115 in 30 patients in the FAIT group and 113 in 29 patients in the BST group. None of the deaths were related to the study therapy. CONCLUSIONS: FAIT exerts modest antitumor effects and poses no particular safety concerns. FAIT may be a strategy of choice worth trying for advanced HCC with high degree of vascular invasion, which is associated with poor prognosis. PMID- 22044787 TI - The use of virtual reality for episodic memory assessment: effects of active navigation. AB - Episodic memory was assessed using Virtual Reality (VR). Forty-four (44) subjects visualized a target virtual apartment containing specific objects in each room. Then they visualized a second virtual apartment comprised of specific objects and objects shared by the two apartments. Subjects navigated in the virtual apartments in one of the following two conditions: active and passive. Four main episodic memory components were scored from the VR exposures: (1) learning effect; (2) active forgetting effect; (3) strategies at encoding and at retrieval; and (4) false recognitions (FRs). The effect of navigation mode (active vs. passive) on each memory component was examined. Active subjects had better learning and retrieval (recognition hits) performances compared to passive subjects. A beneficial effect of active navigation was also observed on the source-based FR rates. Active subjects made fewer source-based FRs compared to passive subjects. These overall results for the effect of active navigation are discussed in terms of the distinction between item-specific and relational processing. PMID- 22044788 TI - Influence of temporal overlap on time course of the Simon effect. AB - Two experiments are reported in which we manipulated relevant and irrelevant stimulus dimensions to assess whether an increase in temporal overlap would influence the time course of a "standard" Simon effect (obtained when visual stimuli are presented on the left/right of the screen and left/right responses are performed with uncrossed hands). This procedure is new in two ways: First, the manipulations were intended to reduce, instead of increase, the distance between conditional and unconditional response-activation processes. Second, we manipulated the relevant and irrelevant stimulus dimensions in a manner that did not vary stimulus onset asynchronies, precues, or go/no go trials, or alter the stimulus quality. Results were consistent with the hypothesis that when the two response processes are shifted closer to each other, the Simon effect would be sustained across time, instead of decreasing as typically found. These findings are discussed in line with the temporal overlap hypothesis and with an automatic activation account. PMID- 22044789 TI - Space-time compatibility effects in the auditory modality. AB - Previous research suggests that past and future temporal concepts are spatially represented from left to right along a mental line. And these concepts can both prime motor responses to left or right space and direct visual spatial attention. The present study aimed at investigating the nature of this space-time conceptual metaphor in different auditory tasks. In the first experiment, subjects categorized time-related words (past or future) that were presented binaurally. In the second experiment, subjects detected left-ear or right-ear targets following time-related words. The similar space-time compatibility effects were found in these two experiments. Our results demonstrate that the activation of temporal concepts can both prime motor responses to left or right space and influence the orientation of auditory spatial attention, suggesting that the modality of the stimulus input is unimportant for the left-right mapping of time. These results are explained by the "intermediate coding" account. PMID- 22044790 TI - On coding the position of letters in words: a test of two models. AB - Open-bigram and spatial-coding schemes provide different accounts of how letter position is encoded by the brain during visual word recognition. Open-bigram coding involves an explicit representation of order based on letter pairs, while spatial coding involves a comparison function operating over representations of individual letters. We identify a set of priming conditions (subset primes and reversed interior primes) for which the two types of coding schemes give opposing predictions, hence providing the opportunity for strong scientific inference. Experimental results are consistent with the open-bigram account, and inconsistent with the spatial-coding scheme. PMID- 22044791 TI - Twenty-four hours of total sleep deprivation selectively impairs attentional networks. AB - Performance decrements after sleep loss have been extensively studied and are usually attributed to generic attentional deficits. This claim, however, is based on the view of attention as a unitary construct, despite evidence that it should be considered a multidimensional cognitive ability. The aim of the present study was to evaluate the impact of one night of sleep deprivation on the efficiency of three attentional networks, defined by Posner and Raichle (1994) in anatomical and functional terms, as alerting, orienting, and executive control. Thirty participants performed the Attention Network Test at 9:00 a.m. following two different sleep conditions: baseline (a normal night of sleep) and deprivation (24 hrs of wakefulness). Results showed an overall slowing in reaction times and a significant decrease in accuracy after sleep deprivation. Sleep deprivation selectively affected the three attentional networks, given that only executive control efficacy significantly decreased after sleep deprivation. By contrast, phasic alerting and orienting showed no differences in the two sleep conditions. Thus, performance deficits following sleep deprivation do not reflect global attentional deficits. PMID- 22044792 TI - Double cardiac silhouette on lateral chest x-ray graphy. PMID- 22044794 TI - A prospective registry of European haemophilia B patients receiving nonacog alfa, recombinant human factor IX, for usual use. AB - Nonacog alfa, a recombinant factor IX (FIX) used for the treatment of haemophilia B, was approved in Europe in 1998. In accordance with European Medicines Agency requirements, a registry study was conducted from 2002 to 2009. A reformulated iso-osmotic version was approved for European use in 2007. This study was conducted to evaluate the safety of nonacog alfa in a usual care setting, and provide clinical trial and postmarketing surveillance data support. This open label, non-interventional, prospective observational cohort study (registry) comprised 52 sites in nine European countries. Patients with haemophilia B receiving nonacog alfa in either formulation for prevention or treatment were followed on a usual care schedule. A total of 218 patients were enrolled, of whom 66 (30.3%) were <18 years of age. Haemophilia severity was evenly distributed, with baseline FIX activity of <1%, 1-5% and >5% in 33.3%, 36.6% and 30.1% of patients, respectively. One hundred thirty-eight patients received the original formulation alone; 80 switched to or received only the new formulation. There was a low incidence of events of special interest (ESIs), with less-than-expected therapeutic effect in five patients (2.2%), inhibitor development in two (0.9%), thrombosis in one (0.5%) and allergic events in eight (3.7%). These accounted for the majority of the 15 serious AEs reported in six patients. Six patients discontinued because of AEs, primarily related to hypersensitivity. Nonacog alfa was shown to be safe for the treatment of haemophilia B, with a low incidence of serious AEs and ESIs. PMID- 22044795 TI - Meta-analysis: vertebroplasty for vertebral compression fracture ineffective in improving pain and function. PMID- 22044797 TI - Social support needs for equity in health and social care: a thematic analysis of experiences of people with chronic fatigue syndrome/myalgic encephalomyelitis. AB - BACKGROUND: Needs-based resource allocation is fundamental to equitable care provision, which can meet the often-complex, fluctuating needs of people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This has posed challenges both for those providing and those seeking support providers, in building shared understanding of the condition and of actions to address it. This qualitative study reports on needs for equity in health and social care expressed by adults living with CFS/ME. METHODS: The participants were 35 adults with CFS/ME in England, purposively selected to provide variation in clinical presentations, social backgrounds and illness experiences. Accounts of experienced needs and needs-related encounters with health and social services were obtained through a focus group (n = 6) and semi-structured interviews (n = 35). These were transcribed and needs related topics identified through data-led thematic analysis. FINDINGS: Participants emphasised needs for personalised, timely and sustained support to alleviate CFS/ME impacts and regain life control, in three thematic areas: (1) Illness symptoms, functional limitations and illness management; (2) practical support and social care; (3) financial support. Access of people with CFS/ME to support from health and social services was seen to be constrained by barriers stemming from social, cultural, organisational and professional norms and practices, further heightened for disadvantaged groups including some ethnic minorities. These reduced opportunities for their illness to be explained or associated functional limitations and social disadvantages to be addressed through social support. Participants sought more understanding of bio-psycho-social aspects of CFS/ME, of felt needs of people with CFS/ME and of human rights and disability rights, for providing person-centred, equitable care. CONCLUSIONS: Changes in attitudes of health practitioners, policy makers and general public and more flexibly organised health and social care provision are needed to address equity issues in support needs expressed by people with CFS/ME, to be underpinned by research-based knowledge and communication, for public and professional education. Policy development should include shared decision-making and coordinated action across organizations working for people with CFS/ME, human rights and disadvantaged groups. Experiences of people with CFS/ME can usefully inform an understanding of equity in their health and social care. PMID- 22044796 TI - Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells. AB - BACKGROUND: Tumor Necrosis Factor-alpha Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. METHODS: FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. RESULTS: Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 MUM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells. CONCLUSIONS: The identification of a number of FDA-approved drugs as TRAIL sensitizers can expand chemotherapeutic options for combination treatments in prostate and pancreatic cancer diseases. PMID- 22044798 TI - Structure-activity relationship of sphingomyelin analogs with sphingomyelinase from Bacillus cereus. AB - The aim of this study was to examine how structural properties of different sphingomyelin (SM) analogs affected their substrate properties with sphingomyelinase (SMase) from Bacillus cereus. Using molecular docking and dynamics simulations (for SMase-SM complex), we then attempted to explain the relationship between SM structure and enzyme activity. With both micellar and monolayer substrates, 3O-methylated SM was found not to be degraded by the SMase. 2N-methylated SM was a substrate, but was degraded at about half the rate of its 2NH-SM control. PhytoPSM was readily hydrolyzed by the enzyme. PSM lacking one methyl in the phosphocholine head group was a good substrate, but PSM lacking two or three methyls failed to act as substrates for SMase. Based on literature data, and our docking and MD simulations, we conclude that the 3O-methylated PSM fails to interact with Mg(2+) and Glu53 in the active site, thus preventing hydrolysis. Methylation of 2NH was not crucial for binding to the active site, but appeared to interfere with an induced fit activation of the SMase via interaction with Asp156. An OH on carbon 4 in the long-chain base of phytoPSM appeared not to interfere with the 3OH interacting with Mg(2+) and Glu53 in the active site, and thus did not interfere with catalysis. Removing two or three methyls from the PSM head group apparently increased the positive charge on the terminal N significantly, which most likely led to ionic interactions with Glu250 and Glu155 adjacent to the active site. This likely interaction could have misaligned the SM substrate and hindered proper catalysis. PMID- 22044799 TI - Functional redundancy and compensation among members of gap junction protein families? AB - Gap junctions are intercellular conduits for small molecules made up by protein subunits called connexins. A large number of connexin genes were found in mouse and man, and most cell types express several connexins, lending support to the view that redundancy and compensation among family members exist. This review gives an overview of the current knowledge on redundancy and functional compensation - or lack thereof. It takes into account the different properties of connexin subunits which comprise gap junctional intercellular channels, but also the compatibility of connexins in gap junctions. Most insight has been gained by the investigation of mice deficient for one or more connexins and transgenic mice with functional replacement of one connexin gene by another. Most single deficient mice show phenotypical alterations limited to critical developmental time points or to specific organs and tissues, while mice doubly deficient for connexins expressed in the same cell type usually show more severe phenotypical alterations. Replacement of a connexin by another connexin in some cases gave rise to rescue of phenotypical alterations of connexin deficiencies, which were restricted to specific tissues. In many tissues, connexin substitution did not restore phenotypical alterations of connexin deficiencies, indicating that connexins are specialized in function. In some cases, fatal consequences arose from the replacement. The current consensus gained from such studies is that redundancy and compensation among connexins exists at least to a limited extent. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. PMID- 22044800 TI - Trait anxiety and the dynamics of attentional control. AB - According to recent theoretical approaches dispositional anxiety is fundamentally linked to neural mechanisms of cognitive control (Braver et al., 2007; Eysenck et al., 2007). The present study was conducted to further investigate this topic by focusing on the relation between trait anxiety, conflict-processing and dynamic adjustments in attentional allocation. Participants completed a modified version of the face-word Stroop task while an electroencephalogram was recorded. We analyzed behavioral and electrophysiological correlates of conflict processing and conflict-driven modulations in target and distractor processing. Anxiety was not related to general conflict-sensitivity but to individual differences in conflict-driven adjustments in attentional allocation: following a high level of stimulus-response conflict, highly anxious participants allocated more attentional resources to the processing of predominantly task-relevant information and withdrew attention from the processing of predominantly task irrelevant information. Thus, trait anxiety appears to be closely related to individual differences in dynamic adjustments of attentional control. PMID- 22044801 TI - Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints. AB - BACKGROUND: The HIV-1 genome is subject to pressures that target the virus resulting in escape and adaptation. On the other hand, there is a requirement for sequence conservation because of functional and structural constraints. Mapping the sites of selective pressure and conservation on the viral genome generates a reference for understanding the limits to viral escape, and can serve as a template for the discovery of sites of genetic conflict with known or unknown host proteins. RESULTS: To build a thorough evolutionary, functional and structural map of the HIV-1 genome, complete subtype B sequences were obtained from the Los Alamos database. We mapped sites under positive selective pressure, amino acid conservation, protein and RNA structure, overlapping coding frames, CD8 T cell, CD4 T cell and antibody epitopes, and sites enriched in AG and AA dinucleotide motives. Globally, 33% of amino acid positions were found to be variable and 12% of the genome was under positive selection. Because interrelated constraining and diversifying forces shape the viral genome, we included the variables from both classes of pressure in a multivariate model to predict conservation or positive selection: structured RNA and alpha-helix domains independently predicted conservation while CD4 T cell and antibody epitopes were associated with positive selection. CONCLUSIONS: The global map of the viral genome contains positive selected sites that are not in canonical CD8 T cell, CD4 T cell or antibody epitopes; thus, it identifies a class of residues that may be targeted by other host selective pressures. Overall, RNA structure represents the strongest determinant of HIV-1 conservation. These data can inform the combined analysis of host and viral genetic information. PMID- 22044802 TI - Global disparities in cancer care: the ABCD for access and the inverse care law. PMID- 22044803 TI - Human papilloma virus: a new risk factor in a subset of head and neck cancers. AB - Head and neck cancer is the sixth most common malignancy worldwide. Tobacco smoking and alcohol consumption are two well known behavioral risk factors associated with head and neck cancer. Recently, evidence is mounting that infection with human papilloma virus, most commonly human papilloma virus-16 is responsible for a subset of head and neck squamous cell carcinoma especially tumors of tonsillar origin. The molecular pathway used by human papilloma virus to trigger malignant transformation of tissue is different from that of other well known risk factors, i.e. smoking and alcohol, associated with squamous cell carcinoma. Apparently, these subsets of patients with human papilloma virus positive tumor are more likely to have a better prognosis than human papilloma virus negative tumor. Considering this fact, the human papilloma virus infection should be determined in all oropharyngeal cancers since it can have a major impact on the decision making process of the treatment. PMID- 22044804 TI - Bone health in breast cancer survivors. AB - The objective of this paper is to carry out a systemic review of the literature investigating issues related to bone health in survivors of breast cancer. Given the fact that only a fraction of women with breast cancer receive appropriate assessment of their bone health, it is hoped that this review will help raise awareness of bone health concerns in this patient population. Articles published in the English language addressing issues related to bone health in breast cancer were accessed using Pubmed database. Studies were searched using keywords like: "Osteoporosis", "osteopenia", "bone health", "breast cancer", "denosumab" and "bisphosphonates". Current evidence suggests that women who survive their breast cancer are at high risk for significant bone loss. Recent clinical guidelines recommend assessment of bone mineral density (BMD) in high-risk patients. Nonpharmacologic interventions including lifestyle changes, vitamin D and calcium supplements are extremely important. Bisphosphonates, in both oral and parenteral formulations, are increasingly used while new agents, like denosumab, have recently been approved. Due to the widespread use of screening mammography and early detection programs leading to breast cancer diagnosis at a much earlier stage and the recent introduction of more effective anticancer therapy, more women are surviving their breast cancer, which highlights the need for survivorship programs that address issues like bone health. Many recent professional societies are addressing these issues and updating their recommendations and guidelines. PMID- 22044805 TI - Chemotherapy, neurotoxicity, and cognitive changes in breast cancer. AB - Chemotherapy-induced cognitive changes have come under immense speculation in recent years. This mild cognitive impairment evinced in the form of short-term memory loss, and attention and concentration problems, finds itself unavoidably attached to the terms 'chemobrain' or 'chemofog'. The predicament between chemotherapy (CT) and neurotoxicity has been considerably examined and most of its attributes have been documented through neuropsychological studies. Although a sizeable portion of literature now covers this phenomenon, certain methodological reservations come in the way of its full appreciation, limited mostly by standardization issues in neuropsychological studies. The current review discusses some of these issues, with emphasis on the underlying mechanisms of progressing cognitive dysfunction in the breast cancer population, accentuating a frontosubcortical involvement and the use of competent neuropsychological batteries and structural and functional imaging techniques, to analyze the changes associated with chemotherapy. The relevance of prospective longitudinal studies with culture-centric norms has been emphasized, with the need for clinical guidelines, to assess and follow the course of neurotoxicity. Keeping track of the patient's own perceptive cognitive loss will help harmonize the decision-making process during chemotherapy. PMID- 22044806 TI - Clinical outcome of patients with uterine sarcomas. AB - PURPOSE: The aim of our retrospective analysis was to study and report the clinical outcome of patients with uterine sarcoma (US) treated at our center; and to share our experience with literature. MATERIALS AND METHODS: We retrieved the information regarding the patient's demography, clinico-pathological details, treatment given, survival, and complications of all the US patients treated at our center between the years 2000-2008. The three-year overall survival (OS) was determined with respect to various prognostic factors like age, stage of disease, histopathological type, adjuvant RT etc. RESULTS: A total of 50 case records were retrieved for this retrospective analysis. Age ranged from 24 to 75 years with a median of 50 years. Carcinosarcoma was the commonest histopathological type (23/50 patients). FIGO stage distribution was: stage I, 27; stage II, 7; stage III, 12; stage IV, 2; and unknown stage, two patients. Forty-eight patients underwent surgery; 31 received postoperative radiation therapy (PORT) and 16 received chemotherapy therapy. Median follow-up period was 34 months (range 2-69 months). The three-year OS for the entire group of patients was 42%. Stage of the disease, histopathological type, and use of PORT were found significant prognostic factors for survival. CONCLUSION: Although limited by small sample size and retrospective nature, ours is the only study on US being reported from India. Our results have demonstrated FIGO stage of the disease, histopathology and use of PORT to be the significant prognostic factor for survival. Use of chemotherapy in future trials is warranted. PMID- 22044808 TI - Quantitative and qualitative analysis of argyrophilic nuclear organizer regions in follicular cyst, keratocystic odontogenic tumor and ameloblastoma. AB - BACKGROUND: Multicystic ameloblastoma is a benign odontogenic tumor that exhibits a more aggressive behavior than keratocystic odontogenic tumor (KCOT) and follicular cyst. AIM: The purpose of the study was to evaluate the proliferation index nuclear organizer regions (NORs) and their distribution among the four odontogenic lesions with known different clinical invasive behavior. STUDY AND DESIGN: In a descriptive-analytical cross-sectional study, 60 paraffin blocks of odontogenic lesions were prepared for silver nitrate staining. MATERIALS AND METHODS: For the quantitative analysis, 100 cells were counted at *100 and the mean value was calculated. The morphometric analysis of NORs showed that they can be distributed into normal (round to oval-shaped) and abnormal (large, bean shaped and cluster-shaped) groups. One-way analysis of variance (ANOVA) and multiple comparison with Tukey test were used for the statistical analysis of the results. RESULTS: The argyrophilic NOR (AgNOR) numbers in multicystic ameloblastoma, unicystic ameloblastoma, KCOT, and follicular cyst were 7.4 +/- 2.7, 6.1 +/- 2.56, 4.7 +/- 1.84, and 2.82 +/- 1.052, respectively. The difference between ameloblastoma (unicystic and multicystic types) and either_KCOT, or follicular cyst was statistically significant (P<0.001) and, (P=0.001), respectively. In follicular cysts, normal AgNOR dots were not detected outside the nuclei. NOR histological patterns of KCOT were large, bean shaped and rarely cluster shaped and it was cluster-shaped in multicystic and unicystic ameloblastoma. CONCLUSION: The current study suggests that determination of clinical behavior of ameloblastoma in comparison with KCOT and follicular cyst in silver nitrate staining is related to higher proliferation activity and different NORs' distribution pattern. However, further clinical follow-up studies must be performed to prove this. PMID- 22044807 TI - Assessment of quality of life of cancer patients in a tertiary care hospital of South India. AB - BACKGROUND: Quality of Life (QOL) measures have now become a vital part of health outcome appraisal and an effective way of capturing the personal and social context of patients. AIM: To assess the QOL of cancer patients by using a validated questionnaire. SETTINGS AND DESIGN: A prospective study in the medical oncology clinic of a tertiary care hospital of South India. MATERIALS AND METHODS: Patients receiving chemotherapy for different types of cancer were subjected to a validated questionnaire and their responses to the factors of the questionnaire were scored and analyzed. A Chi-square test was performed to assess the effect of age and type of cancer on the QOL of patients. Pearson's correlation was done to assess the factors that had greater influence on the QOL. RESULTS: A total of 32 (15 males; 17 females) patients were included and majority were in the age range of 61-80 years. Eleven types of cancer were identified. About 56% of the patients were assessed to have average QOL and 28% had below average QOL, 9% had above average, and 2 (6.25%) had significantly high QOL. The overall mean QOL score of the study population was 122.38 +/- 13.86. Factors 1 (psychological well-being), 2 (self-adequacy), 3 (physical wellbeing), 4 (confidence in self-ability), 6 (pain), 7 (mobility), and 8 (optimism and belief) had significant influence on the QOL, while factors 5 (external support), 9 (interpersonal relationship), and 10 (self-sufficiency and independence) did not have a significant effect on QOL. Age (P=0.396) and type of cancer (P=0.371) did not have a significant effect on the QOL. CONCLUSION: The study showed that 80% of the total study population reported to have average and below average QOL, suggesting that an increasing importance is given to the incorporation of Quality of Life as an outcome, in addition to other clinical endpoints. PMID- 22044809 TI - Study of the cytogenetic and non-cytogenetic factors in cervical carcinoma in the Jammu region of J and K state. AB - AIM: The present study was aimed to analyze the chromosomal changes and also to work out the association of some of the non-cytogenetic factors in the confirmed cases of cervical carcinoma. MATERIALS AND METHODS: Slides for the chromosome study were prepared from the tumor growths of 78 patients as the diagnosed cases of cervical carcinoma. The slides so prepared were then subjected to G-banding to rule the involvement of different chromosomes in the progression of cervical cancer. Non-cytogenetic factors that are considered to be the risk factors for CaCx were also taken up during the present study to study the etiology of cervical cancer. RESULTS: Both the numerical and the structural chromosomal changes have been recorded in a majority of these growths. In most of the cases, numerical chromosomal changes (95%) outnumbered the structural aberrations. DISCUSSION: Aneuploidy was the most common numerical chromosomal aberration recorded in the majority of the tumor growths. Structural aberrations included translocations and deletions. Non-cytogenetic factors like multiparity, early marriage, poor genital hygiene and rural background were highly prevalent in the present study. PMID- 22044810 TI - Inter and intraobserver variation in gross tumor delineation on megavoltage CT images in patients undergoing tomotherapy-based image-guided radiotherapy for postoperative vault recurrences. AB - PURPOSE: This study was designed to evaluate inter and intraobserver concordance in gross tumor volume (GTV) delineation on megavoltage CT (MVCT) images in patients with postoperative vault recurrences. MATERIALS AND METHODS: Three observers delineated GTV on MVCT and CECT and two observers recontoured on MVCT images. Tumor volumes were calculated and correlated using Spearman correlation. The standard deviation of centre of mass was averaged on per patient basis. The ratio of common volume and encompassing volume was used to determine intra and interobserver spatial concordance. Lack of difference in spatial concordance ratio between MVCT and CECT images was used as an index of usability of MVCT images. RESULTS: Thirty six datasets were available for seven patients. High intraobserver GTV correlation was recorded for observer 1 and 2 (r = 0.93 and r = 0.98; P=0.03 and 0.0001). The average intraobserver spatial concordance ratio was 0.57 and 0.62 respectively. The mean GTV of observers 1, 2 and 3 were 31.6 (18.7 52.2); 28.2 (16.7-51.8) and 46.3 cc (29.1-90.5) respectively. Average standard deviation of centre of mass of all observers was less than 5 mm in either direction. Largest interobserver discordance was observed in anterior, inferior and lateral direction. The interobserver spatial concordance of GTV on MVCT and CECT images was 0.34 and 0.36 (P=0.24) respectively. CONCLUSION: Moderate to good inter and intraobserver GTV correlation was observed on MVCT images, however, was associated with low interobserver spatial concordance on both MVCT and CECT images. Strategies to improve contouring reproducibility on MVCT and KVCT images are desirable. PMID- 22044811 TI - Additional rectal and sigmoid mucosal points and doses in high dose rate intracavitary brachytherapy for carcinoma cervix: a dosimetric study. AB - BACKGROUND: Late rectal and sigmoid toxicities seen in cervical cancer patients are attributed to brachytherapy despite rectal doses within tolerance limits. The purpose of this study was to identify additional dosimetric points which may better forecast rectal complications. MATERIALS AND METHODS: Fifteen high dose rate intracavitary brachytherapy (ICA-HDR) applications with conventional X-ray and computed tomography (CT) based planning were studied. In addition to International Commission on Radiation Units and Measurement (ICRU) rectal and bladder points, proximal and distal rectal and sigmoid points were digitized on CT scans and dose volume histograms' (DVHs') parameters were computed and correlated. RESULTS: The mean ICRU, additional distal, proximal and sigmoid point doses were 486 +/- 152 cGy, 527 +/- 156 cGy, 401 +/- 149 cGy and 838 +/- 254 cGy, respectively, for a prescription of 700 cGy to point A. The mean sigmoid point dose was significantly higher than the ICRU rectal point doses (P=0.001). The high-dose sigmoid points were situated at a mean -8 mm (range -22.95 to 10.43 mm) lateral, 10 mm posterior (range -15.87 to 27.82 mm) and 31 mm (range 8.08-62.91 mm) cranial to the intracavitary applicator flange of central tandem. CONCLUSIONS: Our dosimetric study suggests that sigmoid points and 0.1 cm 3 receive significantly higher doses than rectal points during ICA-HDR in carcinoma of the uterine cervix. No definite conclusion on reproducible spatial distribution on orthogonal X-rays could be achieved. To document and reduce sigmoid doses, some form of 3D image-based planning is necessary. PMID- 22044812 TI - A comparative study to evaluate the efficacy of on board imaging with cone beam CT using target registration in patients with lung tumors undergoing stereotactic body radiation therapy and comparison with ExacTrac using skeletal registration on Novalis Tx. AB - BACKGROUND: Stereotactic body radiation therapy is an advanced technique, which delivers ablative doses to lung lesions. Target verification is done either by orthogonal x-rays or cone beam CT. This study was undertaken to compare these two verification methods. AIM: To evaluate the efficacy of ExacTrac and Cone Beam Computed Tomography (CBCT) for target repositioning while delivering Stereotactic Body Radiation Therapy (SBRT) for lung lesions and derive the population-based margin. MATERIALS AND METHODS: All patients who had undergone SBRT for lung lesions from February to September 2009 were involved. Patients were immobilized using the BodyFix double vacuum immobilization system, indexed to the computed tomography (CT) simulator and treatment machine. Four-dimensional (3-D) scan was done to generate internal target volume (ITV) and a free breathing CT scan for planning was done on the BrainLab iPlan 4.1 software. During treatment, patient's position was verified using ExacTrac and CBCT. The resulting vertical, lateral, and longitudinal shifts were noted. The random and systematic error were calculated and the margin recipe derived using the Van Herk formula. RESULTS: Sixteen patients had undergone SBRT for lung tumors from February to September 2009. Data from eight patients who had undergone 34 sessions of SBRT was analyzed. The systematic error for lateral, longitudinal, and vertical shifts for ExacTrac and CBCT were 3.68, 4.27, 3.5 mm and 0.53, 0.38, 0.70 mm, respectively. The random error were 1.10, 1.51, 1.96 mm and 0.32, 0.81, 0.59 mm. The lateral, longitudinal and vertical Van Herk margin recipe for ExacTrac were 9.98, 11.72, 10.18 mm, respectively, and for CBCT was 2.17, 1.53,1.55 mm. CONCLUSIONS: The systematic and random errors for CBCT were significantly lesser as compared to the errors with Exactrac. PMID- 22044813 TI - Estimation of inhomogenity correction factors for a Co-60 beam using Monte Carlo simulation. AB - AIM: The aim was to obtain inhomogenity correction factors (ICFs) for lung tissue inhomogenity for a Co-60 teletherapy beam using Monte Carlo simulation and to compare them with factors obtained from a commercially available treatment planning system. MATERIALS AND METHODS: The Monte Carlo simulation code of EGSnrc is used for the depth dose calculations. Two clinical like situations were simulated-dose calculation point beyond the lung tissue volume and dose calculation point within the lung tissue volume. The variation of ICF with lung thicknesses and positions was studied. ICF values were obtained for the similar situations from a commercially available treatment planning system, Theraplan Plus. RESULTS: Percentage depth dose data obtained from Monte Carlo simulation is well matching with the published measurement data. ICFs for lung tissue inhomogenity calculated using the Monte Carlo code are in good agreement with Theraplan Plus TPS values for small inhomogenity thicknesses. CONCLUSION: These results can be used for the verification of TPS calculation or manual treatment time calculation. PMID- 22044814 TI - In vitro and in vivo targeted delivery of photosensitizers to the tumor cells for enhanced photodynamic effects. AB - BACKGROUND: Efficacy of photodynamic therapy can be enhanced by improving uptake, localization, and sub-cellular localization of sensitizers at the sensitive targets. MATERIALS AND METHODS: Uptake, localization, and photodynamic effects of hematoporphyrin derivative (HpD, Photosan-3; PS-3) and disulfonated aluminum phthalocyanine (AlPcS2) were studied either encapsulated in liposomes or conjugated to a monoclonal antibody to carcinoembryonic antigen (anti-CEA) in a brain glioma cell line, BMG-1. RESULTS: Although the total uptake with encapsulated or conjugated sensitizers was less than the free sensitizers, photodynamic efficiency was higher due to the localization of the sensitizer at the sensitive targets. Biodistribution of intravenously administered technetium (99m Tc)-labeled PS-3 analyzed by gamma camera imaging showed maximum accumulation in the liver followed by tumor. Tumor/muscle (T/N) ratio of free PS 3 was higher compared to encapsulated or conjugated PS-3 but the accumulation of PS-3 significantly reduced in brain and cutaneous tissue following modulated delivery. Pharmacokinetics suggested faster accumulation of encapsulated and conjugated PS-3 in the tumor. CONCLUSION: Localization of sensitizers at sensitive targets and reduced accumulation in normal tissues with liposome encapsulation and antibody conjugation suggest that these two delivery systems can potentially enhance the efficacy of photodynamic treatment. PMID- 22044815 TI - Survivin-deltaEx3: a novel biomarker for diagnosis of papillary thyroid carcinoma. AB - CONTEXT: The most important problem in the case of thyroid nodules is the lack of suitable criteria for detecting malignant thyroid tumors from other nodules in the early stage. Variable expressions level of survivin, an inhibitory protein in apoptotic pathway, and its splice variants in malignant carcinoma versus well differentiated normal tissues candidate them as reliable biomarkers in cancers. AIM: To semi-quantitative detection of survivin and its splice variant, survivin deltaEx3, in thyroid nodules. SETTING AND DESIGN: We evaluated the expression level of mentioned biomarkers in thyroid nodules including carcinoma. MATERIALS AND METHODS: Samples were collected from 61 thyroid nodules including malignant, adenoma, non-tumoral (goiter and thyroidities) as well as non-neoplastic normal tissues. Transcriptional levels were measured using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and the results were normalized to beta2microglubin (beta2m) gene. STATISTICAL ANALYSIS USED: Independent sample t-test was used to assess the significant variation of expression between different groups. RESULT: Our data for a first time revealed that survivin deltaEx3 is significantly up-regulated from normal to malignant thyroid carcinoma tissues (approximately ten fold). CONCLUSION: High expression level of survivin and survivin-deltaEx3 in malignant papillary thyroid carcinoma suggested survivin gene expression and its splice variant, survivin-deltaEx3, can be potential new markers in diagnosis of human papillary thyroid carcinoma. PMID- 22044816 TI - Invasion is not an independent prognostic factor in high-grade glioma. AB - PURPOSE: The role of invasion as a prognostic factor in high-grade gliomas (HGG) remains controversial. An apparent increase in invasiveness following anti angiogenic therapy makes this question clinically relevant. The goal of this study is to assess survival differences in patients with newly diagnosed HGG who present with diffuse invasive disease compared to those who did not, but went on to develop diffuse invasive disease following bevacizumab therapy. MATERIALS AND METHODS: Twenty-three patients presented as newly diagnosed diffuse invasive HGG. All patients underwent surgical resection with radiation therapy and temozolomide for one year. Progression-free survival (PFS) and overall survival (OS) were compared to a control of 58 patients with focal high-grade glioma who received similar therapy, but that included bevacizumab at 10 mg/kg given every two weeks. RESULTS: The patient characteristics were similar in each group. The median PFS and OS for invasive HGG patients were 6 and 13 months and for the focal HGG patients, 11 and 24 months, respectively (P=0.092 and P=0.071). In the subgroup of invasive HGG that showed significant angiogenesis, the median PFS and OS were 3 and 9 months, respectively. 56% of the focal HGG patients recurred as diffuse invasive relapse. For patients with focal HGG who recurred as invasive disease, the median PFS and OS were 9 and 21 months respectively. CONCLUSIONS: Presence of diffuse invasive disease not accompanied by angiogenesis either prior to therapy or subsequent to anti-angiogenic therapy does not seem to have prognostic significance. However, invasion accompanied by angiogenesis in newly diagnosed HGG may confer a poor prognosis. PMID- 22044817 TI - Malignant melanoma with osteoclast-like giant cells: A report of two cases. PMID- 22044818 TI - Adult T-cell leukemia in India: report of two cases and review of literature. PMID- 22044819 TI - Fluoro-deoxy glucose-avid endobronchial inflammatory myofibroblastic tumor mimicking bronchial malignancy: report of a case. PMID- 22044820 TI - Large cell neuroendocrine carcinoma of the retromolar trigone. PMID- 22044821 TI - Rituximab induced myocardial infarction: A fatal drug reaction. PMID- 22044822 TI - A rare cause of acute abdomen: perforated primary sarcomatoid carcinoma of the small intestine - report of a case, with a brief review of the literature. PMID- 22044823 TI - Synchronous primary gall bladder carcinoma and renal transitional cell carcinoma in the same patient: a rare case. PMID- 22044824 TI - Solid alveolar rhabdomyosarcoma with spindle-shaped cells and epithelial differentiation of the mediastinum in a 68-year-old man: a case report and literature review. PMID- 22044825 TI - Carcinoma cervix with metastasis to the orbit: a case report and review of literature. PMID- 22044826 TI - Adenocarcinoma lung in a painter. PMID- 22044827 TI - Fluorodeoxyglucose positron emission tomography-computed tomography scan and nuclear magnetic resonance findings in a case of Stewart-Treves syndrome. PMID- 22044828 TI - A fatal case of pure giant cell carcinoma of the lung. PMID- 22044829 TI - Oncological progression of bone plasmacytoma to POEMS syndrome. PMID- 22044830 TI - Malignant melanotic neuroectodermal tumor of infancy arising in the mandible. PMID- 22044831 TI - Mantle cell lymphoma presenting as Mikulicz syndrome. PMID- 22044832 TI - Giant solitary fibrous tumor of the mesentery: a rare case. PMID- 22044833 TI - Giant axillary swelling alongwith multiple ulcers: primary malignant adnexal tumor-a rare distinct clinicopathologic entity. PMID- 22044834 TI - Off-label use of chemotherapy drugs: look before you leap. PMID- 22044835 TI - Choriocarcinoma with brain involvement. PMID- 22044837 TI - Primary paraganglioma of thyroid presenting as solitary thyroid mass. PMID- 22044838 TI - Second primary malignancy of breast in a patient of gastrointestinal stromal tumor presenting as fluoro-deoxyglucose-avid breast incidentaloma in fluoro deoxyglucose-positron emission tomography. PMID- 22044839 TI - Hand-mirror cell morphology of T-cell lymphoproliferative disorder presenting in pleural effusion with mediastinal widening. PMID- 22044840 TI - Anticancer drug irinotecan inhibits homomeric 5-HT3A and heteromeric 5-HT3AB receptor responses. AB - It has been shown that anti-cancer drug induces secretion of serotonin (5-HT) from small intestine which activates serotonin type 3 (5-HT(3)) receptor to cause nausea and vomiting. In general, antagonist for 5-HT(3) receptor is used as anti emetics during chemotherapy. However, we found that anti-cancer drug irinotecan itself inhibits 5-HT-gated current through the homomeric 5-HT(3A) and heteromeric 5-HT(3AB) receptor in a concentration-dependent manner. The inhibitory effect of irinotecan on 5-HT(3A) receptor was more potent than that on 5-HT(3AB) receptor. On the other hand, SN-38, a metabolite of irinotecan, had no effect on the responsiveness. Our findings suggest that irinotecan itself could have anti emetic activities through inhibition of the 5-HT(3A) and 5-HT(3AB) receptor. PMID- 22044842 TI - Factors associated with physical activity in patients with osteoarthritis of the hip or knee: a systematic review. AB - OBJECTIVE: To give an overview of factors related to the level of physical activity in patients with hip or knee osteoarthritis (OA). METHODS: An extensive systematic literature search was conducted in PubMed, CINAHL and Embase. Inclusion criteria were: studies on patients with a diagnosis of OA of hip and/or knee, studies describing factors related to physical activity (objective or subjective), full length articles that were published in Dutch, German or English language. Two reviewers independently assessed the methodological quality. A best evidence synthesis was performed for factors which were investigated in two or more studies. RESULTS: Eight studies were included, all with a cross-sectional design (five high quality and three low quality studies), resulting in, at most, limited evidence in the best-evidence synthesis. For patients with knee OA there is limited evidence that a lower level of physical function is associated with a lower level of physical activity. There is also limited evidence that depression is not associated with the level of physical activity. For patients with hip OA there is limited evidence that higher age, higher body mass index (BMI) and a low level of physical function is associated with a low level of physical activity. CONCLUSION: A high age (hip OA), a high BMI (hip OA) and a low level of physical function (both hip and knee OA) are related to a low level of physical activity. However, the level of evidence was only limited. Before new strategies and interventions to increase physical activity in patients with OA can be developed, high quality longitudinal studies are needed to get more insight in the causality between factors and low levels of physical activity. PMID- 22044841 TI - The diagnostic performance of MRI in osteoarthritis: a systematic review and meta analysis. AB - OBJECTIVE: Osteoarthritis (OA) is currently diagnosed using clinical and radiographic findings. In recent years magnetic resonance imaging (MRI) use in OA has increasingly been studied. This study was conducted to determine the diagnostic utility of MRI in OA through a meta-analysis of published studies. METHODS: A systematic literature search was undertaken to include studies that used MRI to evaluate or detect OA. MRI was compared to various reference standards: histology, arthroscopy, radiography, CT, clinical evaluation, and direct visual inspection. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) area under the curve (AUC) were calculated. Random-effects models were used to pool results. RESULTS: Of 20 relevant studies identified from the literature, 16 reported complete data and were included in the meta-analysis, with a total of 1220 patients (1071 with OA and 149 without). Overall sensitivity from pooling data of all the included studies was 61% [95% confidence interval (CI) 53-68], specificity was 82% (95% CI 77-87), PPV was 85% (95% CI 80-88), and NPV was 57% (95% CI 43-70). The ROC showed an AUC of 0.804. There was significant heterogeneity in the above parameters (I(2)>83%). With histology as the reference standard, sensitivity increased to 74% and specificity decreased to 76% compared with all reference standards combined. When arthroscopy was used as the reference standard, sensitivity increased to 69% and specificity to 93% compared with all reference standards combined. CONCLUSION: MRI can detect OA with an overall high specificity and moderate sensitivity when compared with various reference standards, thus lending more utility to ruling out OA than ruling it in. The sensitivity of MRI is below the current clinical diagnostic standards. At this time standard clinical algorithm for OA diagnosis, aided by radiographs appears to be the most effective method for diagnosing OA. PMID- 22044843 TI - Effect of body mass index-z score on adverse levels of cardiovascular disease risk factors. AB - BACKGROUND: Cardiovascular disease (CVD) risk factors are associated with body mass index z-score (BMISD) and/or insulin resistance (IR). However, the correlation between adverse levels of these risk factors and BMISD, and the effect of IR on these associations are not fully understood in children. The aim of this study was to evaluate the association between adverse levels of CVD risk factors and BMISD, and the effect of IR on these associations in schoolchildren. METHODS: Conventional CVD risk factors, C-reactive protein (CRP), uric acid (UA) and adiponectin were determined in 757 boys and 494 girls aged between 7 and 12 years. IR was assessed by the homeostasis model approximation index. RESULTS: BMISD were linearly associated with relative risks having adverse levels of all factors, except for glucose and low-density lipoprotein cholesterol (LDL-C) in boys, and except for glucose, LDL-C and adiponectin in girls (P < 0.01-0.001). These associations were weakened after adjustment for IR, but still significant in cases of UA and CRP in boys and UA, high-density lipoprotein cholesterol and CRP in girls (P < 0.01-0.001). CONCLUSION: The relative risk of having adverse levels of most CVD risk factors in school children increased across the entire range of BMISD. IR contributed to most of these relative risks, but BMISD itself also contributed to these relative risks. To prevent future development of CVD, it might be important for schoolchildren to maintain BMISD within normal range. However, in cases of hyper LDL-cholesterolemia, we should consider causes other than BMISD. PMID- 22044844 TI - Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection. AB - BACKGROUND: Bovine dialyzable leukocyte extract (bDLE) is derived from immune leukocytes obtained from bovine spleen. DLE has demonstrated to reduce transcription of Human Immunodeficiency Virus Type 1 (HIV-1) and inactivate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathway. Therefore, we decided to clarify the mode of antiviral action of bDLE on the inhibition of HIV-1 infection through a panel of antiviral assays. RESULTS: The cytotoxicity, HIV-1 inhibition activity, residual infectivity of bDLE in HIV-1, time of addition experiments, fusion inhibition of bDLE for fusogenic cells and the duration of cell protection even after the removal of bDLE were all assessed in order to discover more about the mode of the antiviral action.HIV-1 infectivity was inhibited by bDLE at doses that were not cytotoxic for HeLa-CD4-LTR-beta-gal cells. Pretreatment of HIV-1 with bDLE did not decrease the infectivity of these viral particles. Cell-based fusion assays helped to determine if bDLE could inhibit fusion of Env cells against CD4 cells by membrane fusion and this cell-based fusion was inhibited only when CD4 cells were treated with bDLE. Infection was inhibited in 80% compared with the positive (without EDL) at all viral life cycle stages in the time of addition experiments when bDLE was added at different time points. Finally, a cell-protection assay against HIV 1 infection by bDLE was performed after treating host cells with bDLE for 30 minutes and then removing them from treatment. From 0 to 7 hours after the bDLE was completely removed from the extracellular compartment, HIV-1 was then added to the host cells. The bDLE was found to protect the cells from HIV-1 infection, an effect that was retained for several hours. CONCLUSIONS: bDLE acted as an antiviral compound and prevented host cell infection by HIV-1 at all viral life cycle stages. These cell protection effects lingered for hours after the bDLE was removed. Interestingly, bDLE inhibited fusion of fusogenic cells by acting only on CD4 cells. bDLE had no virucidal effect, but could retain its antiviral effect on target cells after it was removed from the extracellular compartment, protecting the cells from infection for hours.bDLE, which has no reported side effects or toxicity in clinical trials, should therefore be further studied to determine its potential use as a therapeutic agent in HIV-1 infection therapy, in combination with known antiretrovirals. PMID- 22044846 TI - Robust modeling based on optimized EEG bands for functional brain state inference. AB - The need to infer brain states in a data driven approach is crucial for BCI applications as well as for neuroscience research. In this work we present a novel classification framework based on Regularized Linear Regression classifier constructed from time-frequency decomposition of an EEG (electro-encephalography) signal. The regression is then used to derive a model of frequency distributions that identifies brain states. The process of classifier construction, preprocessing and selection of optimal regularization parameter by means of cross validation is presented and discussed. The framework and the feature selection technique are demonstrated on EEG data recorded from 10 healthy subjects while requested to open and close their eyes every 30 s. This paradigm is well known in inducing Alpha power modulations that differ from low power (during eyes opened) to high (during eyes closed). The classifier was trained to infer eyes opened or eyes closed states and achieved higher than 90% classification accuracy. Furthermore, our findings reveal interesting patterns of relations between experimental conditions, EEG frequencies, regularization parameters and classifier choice. This viable tool enables identification of the most contributing frequency bands to any given brain state and their optimal combination in inferring this state. These features allow for much greater detail than the standard Fourier Transform power analysis, making it an essential method for both BCI proposes and neuroimaging research. PMID- 22044845 TI - The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer. AB - BACKGROUND: HER2/neu is an oncogene that facilitates neoplastic transformation due to its ability to transduce growth signals in a ligand-independent manner, is over-expressed in 20-30% of human breast cancers correlating with aggressive disease and has been successfully targeted with trastuzumab (Herceptin(r)). Because trastuzumab alone achieves only a 15-30% response rate, it is now commonly combined with conventional chemotherapeutic drugs. While the combination of trastuzumab plus chemotherapy has greatly improved response rates and increased survival, these conventional chemotherapy drugs are frequently associated with gastrointestinal and cardiac toxicity, bone marrow and immune suppression. These drawbacks necessitate the development of new, less toxic drugs that can be combined with trastuzumab. Recently, we reported that orally administered alpha-tocopheryloxyacetic acid (alpha-TEA), a novel ether derivative of alpha-tocopherol, dramatically suppressed primary tumor growth and reduced the incidence of lung metastases both in a transplanted and a spontaneous mouse model of breast cancer without discernable toxicity. METHODS: In this study we examined the effect of alpha-TEA plus HER2/neu-specific antibody treatment on HER2/neu expressing breast cancer cells in vitro and in a HER2/neu positive human xenograft tumor model in vivo. RESULTS: We show in vitro that alpha-TEA plus anti HER2/neu antibody has an increased cytotoxic effect against murine mammary tumor cells and human breast cancer cells and that the anti-tumor effect of alpha-TEA is independent of HER2/neu status. More importantly, in a human breast cancer xenograft model, the combination of alpha-TEA plus trastuzumab resulted in faster tumor regression and more tumor-free animals than trastuzumab alone. CONCLUSION: Due to the cancer cell selectivity of alpha-TEA, and because alpha-TEA kills both HER2/neu positive and HER2/neu negative breast cancer cells, it has the potential to be effective and less toxic than existing chemotherapeutic drugs when used in combination with HER2/neu antibody. PMID- 22044847 TI - Signals from intraventricular depth electrodes can control a brain-computer interface. AB - A brain-computer interface (BCI) is a device that enables severely disabled people to communicate and interact with their environments using their brain waves. Most research investigating BCI in humans have used scalp-recorded electroencephalography (EEG). We have recently demonstrated that signals from intracranial electrocorticography (ECoG) and stereotactic depth electrodes (SDE) in the hippocampus can be used to control a BCI P300 Speller paradigm. We report a case in which stereotactic depth electrodes positioned in the ventricle were able to obtain viable signals for a BCI. Our results demonstrate that event related potentials from intraventricular electrodes can be used to reliably control the P300 Speller BCI paradigm. PMID- 22044848 TI - Heme iron from meat and risk of adenocarcinoma of the esophagus and stomach. AB - Iron can cause oxidative stress and DNA damage, and heme iron can catalyze endogenous formation of N-nitroso compounds, which are potent carcinogens. Dietary iron promotes esophageal cancer incidence in animal studies and has been identified as a growth factor for Helicobacter pylori, an established risk factor for stomach cancer. We conducted a population-based case-control study of adenocarcinoma of the esophagus (n=124) and stomach (n=154) and 449 controls in Nebraska. Heme iron and total iron intake were estimated from a food frequency questionnaire and databases of heme and total iron. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for known risk factors. Esophageal cancer was positively associated with higher intakes of heme iron (ORQ4 vs. Q1=3.04, 95% CI: 1.20-7.72; P trend=0.009) and total iron from meat sources (ORQ4 vs. Q1=2.67, 95% CI: 0.99-7.16; P trend=0.050). Risk of stomach cancer was elevated among those with higher intakes of heme iron (ORQ4 vs.Q1=1.99, 95% CI: 1.00-3.95; P trend=0.17) and total iron from meat (OR=2.26, 95% CI: 1.14-4.46; P trend=0.11). Iron intake from all dietary sources was not significantly associated with risk of either cancer. Our results suggest that high intakes of heme and iron from meat may be important dietary risk factors for esophageal and stomach cancer and may partly explain associations with red meat. PMID- 22044850 TI - Antioxidant agents in the prevention of hepatocellular carcinoma. PMID- 22044849 TI - A longitudinal study of the metabolic syndrome and risk of colorectal cancer in postmenopausal women. AB - The metabolic syndrome is associated with increased risk of diabetes and coronary heart disease. Although higher BMI and other related factors have been frequently associated with colorectal cancer, whether the metabolic syndrome is associated with the risk of colorectal cancer is unclear. We therefore assessed the association of the metabolic syndrome with the risk of colorectal cancer in a subsample of participants of the Women's Health Initiative who had repeated measurements of the components of the syndrome at baseline and during follow-up. Women with diabetes at baseline enrollment were excluded. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) at baseline and in time-dependent analyses. Among 4862 eligible women, 81 incident cases of colorectal cancer were identified over a median follow-up of 12 years. Presence of the metabolic syndrome at baseline was associated with increased risk of colorectal cancer (HR 2.15, 95% CI 1.30-3.53) and colon cancer (HR 2.28, 95% CI 1.31-3.98). These associations were largely explained by positive associations of serum glucose and systolic blood pressure with both outcomes. Time-dependent covariate analyses supported the baseline findings. Our results suggest that the positive association of the metabolic syndrome with risk of colorectal cancer is largely accounted for by serum glucose levels and systolic blood pressure. The biological mechanism underlying these associations remains to be clarified. PMID- 22044851 TI - Risk of cancer of unknown primary among immigrants to Sweden. AB - Incidence of cancer of unknown primary (CUP) varies globally, and environmental factors are suspected to be related to its development. Immigrant studies offer insights into disease etiology, but no studies have been published on CUP. We investigated CUP risk in immigrants to Sweden to search for etiological clues. The nationwide Swedish Family Cancer Database was used to calculate standardized incidence ratios for CUP in the first-generation immigrants compared with native Swedes from 1958 to 2008. A total of 2340 patients with CUP were identified among immigrants during a follow-up of 23 million person-years compared with 30 507 patients with CUP identified in native Swedes who were followed for 260 million person-years, showing an overall standardized incidence ratio of 0.88 (95% confidence interval: 0.85-0.93). The median age at immigration was 28 years for men and 27 for women. Significantly lower CUP risks, ranging from 0.18 to 0.89, were mainly observed among Finnish, German, and Asian immigrants. The decreased risks tended to be lower for women compared with men. Danes of both sexes had an increased risk. The increased or decreased CUP risks observed in this novel study suggested that early life environmental risk factors or genetic factors influence the development of CUP. The risk patterns were modified by sex. The observed differences may give clues about incidence rates in countries of origin for which incidence data are lacking. PMID- 22044852 TI - A combination of resveratrol and melatonin exerts chemopreventive effects in N methyl-N-nitrosourea-induced rat mammary carcinogenesis. AB - The neurohormone melatonin is primarily involved in the regulation of circadian rhythms, but also acts as an antioxidant and anticarcinogenic agent, especially in breast cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a widely known polyphenolic agent from red wine, which has been shown to exert antioxidant, anti-inflammatory and anticarcinogenic effects. The objective of this study was therefore to investigate the effects of melatonin in combination with resveratrol in a rat model of experimental mammary carcinogenesis. Female Sprague-Dawley rats aged 31 days were used in the experiment. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea (NMU), which was administered in two intraperitoneal doses (50 mg/kg of body weight). Chemoprevention with resveratrol and melatonin started 2 weeks before the first dose of NMU and lasted until the end of the experiment. The basic parameters evaluated were: tumour incidence, latency period, tumour frequency per group and tumour volume. In addition, oestrogen receptors ERalpha and ERbeta, melatonin receptor MT1, proliferating cell nuclear antigen and vascular endothelial growth factor were determined by immunohistochemical staining. The combination of resveratrol and melatonin reduced tumour incidence by approximately 17% and significantly decreased the quantity of invasive and in-situ carcinomas. Food intake declined in the second and seventh weeks after the administration of carcinogen. Resveratrol in combination with melatonin returned food intake to the level of intact controls. Resveratrol in combination with melatonin has some protective effects on NMU-induced rodent breast cancer. Further studies are necessary to confirm these effects of this promising combination. PMID- 22044853 TI - Human breast tumor slices as an alternative approach to cell lines to individualize research for each patient. AB - There are several breast cancer experimental models including cell lines, which are commonly used due to ease of handling and storage. However, the continued propagation of cell lines and distribution among laboratories results in genetic drift and distancing from the in-vivo model. Primary organ culture of breast cancer slices may produce biological responses with high standard deviation for different samples, reflecting the heterogeneity of different tumors. Thus, the organ culture model system offers a new perspective to the results obtained in the cell lines and offers an alternative for studies that seek to individualize treatment for each patient, an increasingly prominent concern in current cancer therapy. PMID- 22044854 TI - Comparative effectiveness of efavirenz, protease inhibitors, and raltegravir based regimens as first-line treatment for HIV-infected adults: a mixed treatment comparison. AB - OBJECTIVE: Compare the efficacy of 2 NRTIs combined with raltegravir (RAL), efavirenz (EFV), or protease inhibitors (PI) in the management of antiretroviral naive HIV adult patients. METHODS: By means of a systematic literature view, 7 randomized controlled trials were identified: 2 RAL vs EFV trials; 1 ritonavir boosted lopinavir (LPV/RTV) vs EFV trial; 1 ritonavir-boosted atazanavir (ATV/RTV) vs LPV/RTV trial; 1 ritonavir-boosted darunavir (DRV/RTV) vs LPV/RTV trial; 1 ritonavir-boosted fosamprenavir (FPV/RTV) vs LPV/RTV trial; and 1 FPV/RTV vs ATV/RTV trial. Endpoints concerned virological suppression and immunologic efficacy. Trials were analyzed with Bayesian mixed treatment comparison meta-analysis. RESULTS: For up to 24 weeks of treatment, a PI-based regimen resulted in a lower proportion of patients with virological response than an EFV-based regimen, whereas RAL seems more efficacious than EFV up to at least 12 weeks. After 48 weeks, the odds ratio (OR) of virological suppression with RAL relative to EFV was 1.34 (95% credible interval [CrI], 0.87-2.07). ORs for PIs relative to EFV varied from 0.68 (0.41-1.07) with LPV/RTV to 0.99 (0.52-1.84) with DRV/RTV. RAL demonstrated a greater improvement in CD4+ T cell counts than EFV at 48 weeks. The PI regimens showed all similar improvements relative to EFV. CONCLUSION: Based on available RCTs, the fastest virological suppression is expected with RAL followed by EFV and PIs. Over time, RAL appears to be at least as good as PI and EFV regimens. CD4+ cell recovery seems the greatest with LPV/RTV, DRV/RTV, and RAL. Given the limited number of RCTs, additional studies are recommended. PMID- 22044855 TI - Incidence rate of and factors associated with loss to follow-up in a longitudinal cohort of antiretroviral-treated HIV-infected persons: an AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) analysis. AB - PURPOSE: Examine incidence and factors associated with loss to follow-up (LTFU) in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) cohort. METHOD: ALLRT is a prospective cohort of HIV-infected persons randomized to antiretroviral (ARV) regimens/strategies in ACTG trials and followed long-term after the trial ends. Person-years were calculated from ALLRT entry until loss to follow-up (LTFU; defined using off-study reasons or >= 3 consecutive missed visits), death/ severe debilitation/site closures, or June 2009 (censored). Poisson regression was used to examine LTFU factors separately among participants who were ARV naive or ARV experienced at trial entry. RESULTS: Among 4,630 participants (22,524 person-years), 1,140 were lost to follow-up, 237 died, 29 were severely debilitated, and 443 were at sites that closed. The LTFU incidence was 5.5 and 4.2 per 100 person-years among previously ARV-naive and ARV experienced participants, respectively. In both groups, age <= 50, site location, being off ARVs, and viral load >= 400 copies/mL were associated with a higher risk of LTFU. Among ARV-naive participants, male sex, education <16 years, intravenous drug use, and cigarette smoking were also associated with LTFU. CONCLUSION: Knowledge of differential LTFU can help researchers identify participants at risk of LTFU in longitudinal HIV cohorts and design retention strategies, thereby limiting study bias. The identified factors should be included in inverse probability of weighting models to account for LTFU. PMID- 22044857 TI - Assessment of vascular function in HIV-infected patients. AB - PURPOSE: The vascular function in HIV-infected persons under HAART and non-HIV infected persons was investigated. METHOD: 18 HIV-positive patients and 23 HIV negative subjects (14 younger group and 9 older group) were evaluated for microvascular vasodilatation during postocclusive reactive hyperemia (PORH) and during prolonged local thermal hyperemia; overall microvascular flux increase induced by iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and large artery stiffness (SI(DVP)). RESULTS: Cutaneous vascular conductance (CVC) responses to ACh were lower in HIV patients compared to both HIV-negative groups (mean [SEM]) (HIV positive: 878.2 [99.5]; older HIV negative: 1129.3 [231.6]; younger HIV negative: 1366.5 [172.6] % baseline). Regarding SNP iontophoresis, HIV-positive and older HIV-negative groups showed lower CVC responses than younger HIV-negative group (HIV positive: 1043.0 [164.6]; older HIV-negative: 980.8 [108.3]; younger HIV-negative: 1757.3 [245.1] % baseline). Vasodilatation induced by thermal hyperemia (HIV positive: 1.63 [0.11]; older HIV negative: 1.48 [0.08]; younger HIV negative: 1.85 [0.27] perfusion units/mm Hg) and PORH (HIV positive: 0.374 [0.025]; older HIV negative: 0.326 [0.025]; younger HIV negative: 0.326 [0.037] PU/mm Hg) were similar between all groups. SIDVP was greater in HIV and older healthy groups than younger healthy group (HIV positive: 9.17 [0.42]; older HIV negative: 8.19 [0.43]; younger HIV negative: 6.42 [0.22] m/s). CONCLUSION: HIV-infected patients under HAART exhibited slight but nonsignificant lower microvascular reactivity to pharmacological stimuli and increased arterial stiffness compared to age-matched HIV-negative subjects. Comparison of both HIV-positive and older HIV-negative groups with younger HIV negative subjects suggests that age plays a major role in microvascular reactivity regardless the HIV-infection. PMID- 22044856 TI - A randomized clinical trial evaluating therapeutic drug monitoring (TDM) for protease inhibitor-based regimens in antiretroviral-experienced HIV-infected individuals: week 48 results of the A5146 study. AB - BACKGROUND: We devised an open-label, randomized trial to evaluate whether therapeutic drug monitoring (TDM) of protease inhibitors (PIs) and dose escalation based upon a normalized inhibitory quotient (NIQ), which integrates PI trough concentration and drug resistance, could improve virologic outcome in PI experienced patients with treatment failure. Secondary analyses through 48 weeks are presented. METHODS: Eligible HIV-infected subjects with a screening viral load of >= 1000 copies/mL initiated a new PI-based regimen at entry and had NIQ performed at week 2. Subjects with an NIQ <=1 were randomized at week 4 to a standard-of-care (SOC) arm or TDM arm featuring PI dose escalation. RESULTS: One hundred and eighty-three subjects were randomized. There was no significant treatment difference in change from randomization to week 48 in HIV-1 RNA [ P = .13, median (25th, 75th percentile log10 copies/mL change): -0.03 (-0.74, 0.62) with TDM and 0.11 (-2.3, 0.82) with SOC]. In subgroup analysis, patients with >= 0.69 active PIs benefited from TDM compared to those with <0.69 active PIs ( P = .05). CONCLUSIONS: While the TDM strategy of PI dose escalation did not improve virologic response at week 48 overall, in subgroup analysis, TDM favorably impacted virologic outcome in subjects taking PI-based regimens with moderate antiviral activity. PMID- 22044858 TI - Body mass index and CD4+ T-lymphocyte recovery in HIV-infected men with viral suppression on antiretroviral therapy. AB - PURPOSE: To better characterize the relationship between body mass index (BMI) and CD4+ T-lymphocyte recovery in HIV disease. METHODS: We analyzed the association between baseline BMI and CD4+ T-lymphocyte increases, as well as the association between BMI and immune activation (CD38 and HLA-DR co-expression on CD4+ and CD8+ T-lymphocytes), in male HIV-infected patients who achieved viral suppression on antiretroviral therapy (ART). RESULTS: Baseline BMI predicted change in CD4+ T-lymphocyte count at weeks 96 ( P = .03, n = 461) and 144 ( P = .005, n = 357) but not at week 48 ( P = .38, n = 558). Relative to men with a normal BMI, overweight and obese men had increases at week 144 that were 35 and 113 cells/ mm3 higher, respectively, while underweight men had CD4+ T-lymphocyte increases that were 94 cells/mm3 lower. No significant correlations between baseline BMI and cellular immune activation were seen. CONCLUSIONS: BMI predicts CD4+ T-lymphocyte gains in men started on ART. PMID- 22044859 TI - 96-week results of a pilot study of abacavir/lamivudine and raltegravir in antiretroviral-naive HIV-1-infected patients: the SHIELD trial. PMID- 22044862 TI - A prospective comparison of cardiac magnetic resonance imaging and radionuclide ventriculography in the assessment of cardiac function in patients treated with anthracycline-based chemotherapy. AB - PURPOSE: To compare cardiac MRI and radionuclide ventriculography (RVG) in cardiac monitoring during anthracycline (doxorubicin)-based chemotherapy. MATERIALS AND METHODS: We studied 10 previously untreated adult non-Hodgkin lymphoma patients. Left ventricular ejection fraction (LVEF) was assessed by MRI and RVG simultaneously. In addition, left ventricular (LV) and left atrial size were determined by MRI. Both MRI and RVG measurements were determined at baseline and then repeated after eight cycles of CHOP chemotherapy (cumulative doxorubicin dose of 400 mg/m2). Power calculations were made on the basis of reproducibility measurements. RESULTS: Clinical heart failure was not observed in any patient during the study. MRI detected a statistically significant increase in LV end diastolic volume (128 +/- 39 vs. 151 +/- 46 ml, P<0.05) and LV mass (119 +/- 32 vs. 146 +/- 49 g, P<0.05) after doxorubicin therapy but no change in LVEF (46 +/- 8 vs. 47 +/- 11%, P=NS) or left atrial area. A significant LVEF reduction compared with baseline was observed by RVG (61 +/- 10 vs. 50 +/- 6%, P<0.01). On average, MRI resulted in 7 +/- 10% lower LVEF values compared with RVG. CONCLUSION: RVG seems to be a valuable and repeatable tool in detecting early, subclinical deterioration in cardiac function and is the method of choice in the follow-up of LV function during anthracycline-based chemotherapy. Whether LV volumetric and mass changes found in MRI could predict later significant permanent cardiac damage should be evaluated in larger studies with long-term follow-up. PMID- 22044863 TI - Fully automatic synthesis of [18F]FES for reporter gene hERL expression imaging. AB - We have developed a fully automatic method for the synthesis of 16alpha [18F]fluoroestradiol ([F]FES) using a TRACERlab FXFN module. Following [18F]fluorination, the intermediate was hydrolyzed with a mixture of 2 N HCl in acetonitrile (CH3CN) and then neutralized with sodium bicarbonate (NaHCO3). After HPLC purification, the decay-corrected radiochemical yield of [18F]FES was 50 +/- 2.35% (n=4), which was stable up to 96.1 +/- 0.3% (n=4) at 8 h. This new fully automated synthesis method provided high and reproducible yields and the produced [F]FES could be used to monitor in-vivo human estrogen receptor alpha ligand binding domain gene expression using PET images. PMID- 22044864 TI - Evaluation of PET volume segmentation methods: comparisons with expert manual delineations. AB - INTRODUCTION: [18F]-Fluorodeoxyglucose PET has become an essential technique in oncology. Accurate segmentation is important for treatment planning. With the increasing number of available methods, it will be useful to establish a reliable evaluation tool. METHOD: Five methods for [F]-fluorodeoxyglucose PET image segmentation (MIP-based, Fuzzy C-means, Daisne, Nestle and the 42% threshold based approach) were evaluated on non-Hodgkin's lymphoma lesions by comparing them with manual delineations performed by a panel of experts. The results were analyzed using different similarity measures. Intraoperator and interoperator variabilities were also studied. RESULTS: The maximum of intensity projection based method provided results closest to the manual delineations set [binary Jaccard index mean (SD) 0.45 (0.15)]. The fuzzy C-means algorithm yielded slightly less satisfactory results. The application of a 42% threshold-based approach yielded results furthest from the manual delineations [binary Jaccard index mean (SD) 0.38 (0.16)]; the Daisne and the Nestle methods yielded intermediate results. Important intraoperator and interoperator variabilities were demonstrated. CONCLUSION: A simple assessment framework based on comparisons with manual delineations was proposed. The use of a set of manual delineations performed by five different experts as the reference seemed to be suitable to take the intraoperator and the interoperator variabilities into account. The online distribution of the data set generated in this study will make it possible to evaluate any new segmentation method. PMID- 22044865 TI - Ultrasound-guided sentinel node procedure for nonpalpable breast carcinoma. AB - PURPOSE: Peritumoral and periareolar tracer injection techniques lead to different lymphatic drainage in sentinel lymph node biopsy procedures. In a prospective study, the visualization and identification rates of the ultrasound (US)-guided tracer injection technique for palpable and nonpalpable breast tumors were evaluated. METHODS: In 1262 consecutive patients with cT1-2N0 breast cancer, sentinel lymph node biopsy was performed following peritumoral tracer injection. In the case of nonpalpable breast lesions, Tc-99m nanocolloid injections were given using a 7.5 MHz US probe. In the case of ultrasonographically nonvisible microcalcifications, the US-guided injection technique was wire guided. RESULTS: In 331 patients with nonpalpable breast lesions (26.2%), the lymphoscintigraphic visualization and surgical retrieval rates of axillary sentinel lymph nodes (SLNs) were 98.5 and 99.4%, respectively. For internal mammary (IM) SLNs, these rates were 21.1 and 17.8%, respectively. These rates were similar in patients with palpable and nonpalpable tumors. Axillary metastases were detected in 38.7% of the patients with palpable tumors versus 16.5% of those with nonpalpable tumors (P<0.001), whereas IM metastases were found in 4.8 and 3.0% of patients, respectively (P=0.165). CONCLUSION: In nonpalpable breast lesions, the US-guided injection technique is an accurate technique for SLN identification and retrieval. The substantial rates of IM metastases in both palpable and nonpalpable lesions favor a peritumoral tracer injection technique. PMID- 22044866 TI - Cortical metabolites as biomarkers in the R6/2 model of Huntington's disease. AB - To improve the ability to move from preclinical trials in mouse models of Huntington's disease (HD) to clinical trials in humans, biomarkers are needed that can track similar aspects of disease progression across species. Brain metabolites, detectable by magnetic resonance spectroscopy (MRS), have been suggested as potential biomarkers in HD. In this study, the R6/2 transgenic mouse model of HD was used to investigate the relative sensitivity of the metabolite profiling and the brain volumetry to anticipate the disease progression. Magnetic resonance imaging (MRI) and (1)H MRS data were acquired at 9.4 T from the R6/2 mice and wild-type littermates at 4, 8, 12, and 15 weeks. Brain shrinkage was detectable in striatum, cortex, thalamus, and hypothalamus by 12 weeks. Metabolite changes in cortex paralleled and sometimes preceded those in striatum. The entire set of metabolite changes was compressed into principal components (PCs) using Partial Least Squares-Discriminant Analysis (PLS-DA) to increase the sensitivity for monitoring disease progression. In comparing the efficacy of volume and metabolite measurements, the cortical PC1 emerged as the most sensitive single biomarker, distinguishing R6/2 mice from littermates at all time points. Thus, neurochemical changes precede volume shrinkage and become potential biomarkers for HD mouse models. PMID- 22044867 TI - The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism. AB - Normal brain function depends critically on moment-to-moment regulation of oxygen supply by the bloodstream to meet changing metabolic needs. Neurovascular coupling, a range of mechanisms that converge on arterioles to adjust local cerebral blood flow (CBF), represents our current framework for understanding this regulation. We modeled the combined effects of CBF and capillary transit time heterogeneity (CTTH) on the maximum oxygen extraction fraction (OEF(max)) and metabolic rate of oxygen that can biophysically be supported, for a given tissue oxygen tension. Red blood cell velocity recordings in rat brain support close hemodynamic-metabolic coupling by means of CBF and CTTH across a range of physiological conditions. The CTTH reduction improves tissue oxygenation by counteracting inherent reductions in OEF(max) as CBF increases, and seemingly secures sufficient oxygenation during episodes of hyperemia resulting from cortical activation or hypoxemia. In hypoperfusion and states of blocked CBF, both lower oxygen tension and CTTH may secure tissue oxygenation. Our model predicts that disturbed capillary flows may cause a condition of malignant CTTH, in which states of higher CBF display lower oxygen availability. We propose that conditions with altered capillary morphology, such as amyloid, diabetic or hypertensive microangiopathy, and ischemia-reperfusion, may disturb CTTH and thereby flow-metabolism coupling and cerebral oxygen metabolism. PMID- 22044868 TI - Meteorin is a chemokinetic factor in neuroblast migration and promotes stroke induced striatal neurogenesis. AB - Ischemic stroke affecting the adult brain causes increased progenitor proliferation in the subventricular zone (SVZ) and generation of neuroblasts, which migrate into the damaged striatum and differentiate to mature neurons. Meteorin (METRN), a newly discovered neurotrophic factor, is highly expressed in neural progenitor cells and immature neurons during development, suggesting that it may be involved in neurogenesis. Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-D-asparate-induced apoptotic cell death in SVZ cells in vitro. Stroke induced by middle cerebral artery occlusion upregulates the expression of endogenous METRN in cells with neuronal phenotype in striatum. Recombinant METRN infused into the stroke-damaged brain stimulates cell proliferation in SVZ, promotes neuroblast migration, and increases the number of immature and mature neurons in the ischemic striatum. Our findings identify METRN as a new factor promoting neurogenesis both in vitro and in vivo by multiple mechanisms. Further work will be needed to translate METRN's actions on endogenous neurogenesis into improved recovery after stroke. PMID- 22044869 TI - Neurointensive care biophysiological monitoring. AB - Monitoring various physiological parameters and their derangements provides a valuable tool for management of severely brain injured patients. The various parameters and their monitoring tools include but are not all inclusive are cerebral blood flow and oxygen monitoring, jugular bulb oximetry, intracerebral microdialysis and continuous electroencephalography. It needs to be seen how these devices are applied to improve patient outcomes. PMID- 22044870 TI - High rates of depressive symptomatology among injecting drug users in Saskatoon, Canada. PMID- 22044871 TI - An overview of animal prion diseases. AB - Prion diseases are transmissible neurodegenerative conditions affecting human and a wide range of animal species. The pathogenesis of prion diseases is associated with the accumulation of aggregates of misfolded conformers of host-encoded cellular prion protein (PrPC). Animal prion diseases include scrapie of sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, transmissible mink encephalopathy, feline spongiform encephalopathy, exotic ungulate spongiform encephalopathy, chronic wasting disease of cervids and spongiform encephalopathy of primates. Although some cases of sporadic atypical scrapie and BSE have also been reported, animal prion diseases have basically occurred via the acquisition of infection from contaminated feed or via the exposure to contaminated environment. Scrapie and chronic wasting disease are naturally sustaining epidemics. The transmission of BSE to human has caused more than 200 cases of variant Cruetzfeldt-Jacob disease and has raised serious public health concerns. The present review discusses the epidemiology, clinical neuropathology, transmissibility and genetics of animal prion diseases. PMID- 22044872 TI - Maternal exercise decreases maternal deprivation induced anxiety of pups and correlates to increased prefrontal cortex BDNF and VEGF. AB - Maternal deprivation (MD) may cause neuropsychiatric disorders such as anxiety disorder by negatively affecting the cognitive functions and behavior in pups. The aim of this study is to investigate whether maternal exercise during pregnancy has beneficial effects on anxiety that increases with MD, and on the levels of VEGF and BDNF which have anxiolytic effects on the prefrontal cortex, the anxiety-related region of the brain. The anxiety level in the deprivation group was greater than the control group and found more in male than female pups. The prefrontal cortex VEGF and BDNF levels were decreased in the deprivation group compared to control group while serum corticosterone levels were increased in the deprivation group. Anxiety and serum corticosterone levels were decreased in maternally exercised female and male pups, while the prefrontal cortex VEGF and BDNF levels were increased, compared to sedentary mother's pups. These results indicate that maternal exercise may attenuate the negative effect of stresses such as maternal deprivation that can be encountered early in life. PMID- 22044873 TI - Association of biomarkers and depressive symptoms in schizophrenia. AB - Emergence of depressive symptoms in schizophrenia results in a deteriorating course and poor prognosis. Schizophrenia and depressive disorder are both associated with low levels of brain-derived neurotrophic factor (BDNF) and with a longstanding low grade inflammatory state. The objective of this study is to analyze the relationship between these serum biomarkers and depressive and psychotic symptoms in schizophrenic patients. Thirty-nine individuals diagnosed with schizophrenia or schizoaffective disorder by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), assessed by Structured Clinical Interview for DSM-IV (SCID), were included. Interviews were conducted with The Positive and Negative Syndrome Scale (PANSS) and The Calgary Depression Scale for Schizophrenia (CDSS). Blood samples were collected for determination of BDNF, IL 1beta, IL-6, IL-8, IL-10, IL-12 and TNF-alpha measurements. Positive correlations between BDNF and CDSS and between IL-1beta and severity in PANSS scores were found. BDNF levels were not correlated with any cytokine or with PANSS scores. The results of this study suggest that depressive and psychotic symptoms may be associated with different profiles of biomarkers in the association between schizophrenia and depression. PMID- 22044874 TI - The characterization of gene expression during mouse neural stem cell differentiation in vitro. AB - Neural stem cells (NSCs) are tissue-specific, multipotent stem cells that can differentiate into three cell lineages in the central nervous system: neurons, astrocytes and oligodendrocytes. The therapeutic potential of NSCs has fueled attempts to characterize the expression of genes that regulate their fate. In this study, NSCs from embryonic day 15 (E15) mouse embryos were differentiated for 1 (DF-1) or 2 (DF-2) days, and the gene expression patterns in the NSCs and in the DF-1 and DF-2 cells were measured by microarray and real-time RT-PCR. Among the analyzed genes, 1898 genes were up-regulated in the DF-1 and DF-2 cells relative to the NSCs, whereas 1642 genes were down-regulated. The up-regulated genes included Gfap, Smad6, Fst, Tgfb2 and Cdkn2. The down-regulated genes included Ccnb1, Ccnd1 and Ccnd2. We identified gene networks that were associated with BMP and TGF-beta2 signaling pathways using Ingenuity Pathway Analysis. Our results suggest that the differentiation of E15 NSCs into astrocytes is based on a combinatorial network of various signaling pathways, including cell cycle, BMP and TGF-beta2 signaling. PMID- 22044875 TI - Association between 1425G/A SNP in PRKCH and ischemic stroke among Chinese and Japanese populations: a meta-analysis including 3686 cases and 4589 controls. AB - AIMS: Meta-analysis was performed to investigate the association between 1425G/A SNP in PRKCH (the gene encoding for protein kinase C eta) and ischemic stroke among Chinese and Japanese populations. METHODS: The databases of MEDLINE, PubMed, Chinese Biomedical Database, China National Knowledge Infrastructure, and WANFANG DATA until September 2011 were searched for published case-control studies on 1425G/A SNP in PRKCH and ischemic stroke. Strict selection criteria and exclusion criteria were determined, and pooled odds ratio (OR) and the 95% confidence interval (CI) were calculated using a fixed or random effects model to determine the strength of the genetic association. The publication bias was further evaluated by calculating the fail-safe number in the included studies. RESULTS: Five studies, comprising 3686 cases and 4589 controls, passed all the criteria and therefore were included in the meta-analysis. Test for heterogeneity showed that P values (P=0.76, 0.24, respectively) in the two meta-analyses were both greater than 0.05, therefore the fixed effects model was performed. Statistically significant association between 1425G/A SNP in PRKCH and ischemic stroke was identified (OR=1.34; 95% CI, 1.22-1.47), and the association was even stronger between 1425G/A SNP in PRKCH and lacunar infarction (OR=1.44; 95% CI, 1.28-1.63). The fail-safe number (N(fs 0.05)) for 1425G/A SNP in PRKCH with ischemic stroke and lacunar infarction was 59 and 44, respectively, which were greater than the number of studies included in the analyses. CONCLUSIONS: SNP 1425G/A in PRKCH was associated with ischemic stroke, particularly lacunar infarction, in Chinese and Japanese populations. More studies of different subtypes of stroke need to be done to confirm the results in other Asian populations. PMID- 22044876 TI - Increased cutaneous NGF and CGRP-labelled trkA-positive intra-epidermal nerve fibres in rat diabetic skin. AB - In this study we have determined the amount of Nerve Growth Factor (NGF) and the innervation density of the glabrous hindpaw skin of diabetic rats (n=4) and controls (n=3). The proportion of intra-epidermal nerve fibres (IENF) expressing the high affinity NGF receptor (trkA) and calcitonin gene-related peptide (CGRP) were also determined. Four weeks after induction of diabetes by intraperitoneal streptozotocin injection skin was analyzed for: (i) NGF content using ELISA and (ii) the innervation density of peptidergic afferents that also expressed trkA using immunocytochemistry. NGF levels were approximately three-fold higher in diabetic skin compared to controls (diabetic: 134.7+/-24.0 (SD) pgml(-1), control: 42.7+/-21.5pgml(-1), p=0.002). As expected there was a significant reduction in IENF density in diabetic skin (2.7+/-1.3 fibresmm(-1)) compared to controls (6.9+/-1.5 fibresmm(-1); p=0.01). In diabetic rats there was no significant difference in the proportion of trkA-labelled IENF (diabetic 74+/ 21%; control 83+/-15%, p=0.6), but significantly more trkA-positive IENF were also labelled by CGRP antibodies in diabetic skin compared to controls (diabetic 89+/-22%; control 38+/-2%, p=0.03). These data suggest that in diabetes the upregulation of cutaneous NGF may 'over-troph' the surviving axons, increasing CGRP labelling, which may be important in the aetiology of painful diabetic neuropathy. PMID- 22044877 TI - Protective effects of lycopene against amyloid beta-induced neurotoxicity in cultured rat cortical neurons. AB - The neurotoxicity of amyloid beta (Abeta) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). Among antioxidant phytochemicals derived from fruit and vegetables, lycopene has recently received considerable attention for its potent protective properties already demonstrated in several models of oxidative damage. The present study aims to investigate whether lycopene could provide protective effects against Abeta-induced neurotoxicity in primary cultured rat cortical neurons. The cultured cortical neurons were pretreated with different dose of lycopene for 4h, followed by the challenge with 25 MUM Abeta(25-35) for 24h. The results showed that pretreatment with lycopene efficiently attenuated Abeta(25-35)-induced neurotoxicity, as evidenced by the improved cell viability and the decreased apoptotic rate. In addition, lycopene inhibited the reactive oxygen species generation and mitochondrial membrane potential depolarization caused by Abeta(25-35). Lycopene also restored the levels of proapoptotic Bax, antiapoptotic Bcl-2, and inhibited caspase-3 activation. These beneficial effects may contribute to the protection against Abeta-induced neurotoxicity. Together, our results suggest that the natural antioxidant lycopene has potential for neuroprotection and therefore, may be a promising candidate for AD treatment. PMID- 22044878 TI - Dual inhibitors of P-glycoprotein and tumor cell growth: (re)discovering thioxanthones. AB - For many pathologies, there is a crescent effort to design multiple ligands that interact with a wide variety of targets. 1-Aminated thioxanthone derivatives were synthesized and assayed for their in vitro dual activity as antitumor agents and P-glycoprotein (P-gp) inhibitors. The approach was based on molecular hybridization of a thioxanthone scaffold, present in known antitumor drugs, and an amine, described as an important pharmacophoric feature for P-gp inhibition. A rational approach using homology modeling and docking was used, to select the molecules to be synthesized by conventional or microwave-assisted Ullmann C-N cross-coupling reaction. The obtained aminated thioxanthones were highly effective at inhibiting P-gp and/or causing growth inhibition in a chronic myelogenous leukemia cell line, K562. Six of the aminated thioxanthones had GI(50) values in the K562 cell line below 10 MUM and 1-{[2 (diethylamino)ethyl]amino}-4-propoxy-9H-thioxanthen-9-one (37) had a GI(50) concentration (1.90 MUM) 6-fold lower than doxorubicin (11.89 MUM) in the K562Dox cell line. The best P-gp inhibitor found was 1-[2-(1H-benzimidazol-2 yl)ethanamine]-4-propoxy-9H-thioxanthen-9-one (45), which caused an accumulation rate of rhodamine-123 similar to that caused by verapamil in the K562Dox resistant cell line, and a decrease in ATP consumption by P-gp. At a concentration of 10 MUM, compound 45 caused a decrease of 12.5-fold in the GI(50) value of doxorubicin in the K562Dox cell line, being 2-fold more potent than verapamil. From the overall results, the aminated thioxanthones represent a new class of P-gp inhibitors with improved efficacy in sensitizing a resistant P-gp overexpressing cell line (K562Dox) to doxorubicin. PMID- 22044879 TI - Single-unit-cell thick Mn3O4 nanosheets. AB - Single-unit-cell thick Mn(3)O(4) sheets were synthesized in an aqueous solution at room temperature. These nanosheets have a 001 orientation and are terminated at the Mn(2)O(4) atomic layer. Due to the huge shape anisotropy, they demonstrated lower T(C) and much greater coercivity than those of bulk Mn(3)O(4), respectively. PMID- 22044880 TI - Global epigenetic changes during somatic cell reprogramming to iPS cells. AB - Embryonic stem cells (ESCs) exhibit unique chromatin features, including a permissive transcriptional program and an open, decondensed chromatin state. Induced pluripotent stem cells (iPSCs), which are very similar to ESCs, hold great promise for therapy and basic research. However, the mechanisms by which reprogramming occurs and the chromatin organization that underlies the reprogramming process are largely unknown. Here we characterize and compare the epigenetic landscapes of partially and fully reprogrammed iPSCs to mouse embryonic fibroblasts (MEFs) and ESCs, which serves as a standard for pluripotency. Using immunofluorescence and biochemical fractionations, we analyzed the levels and distribution of a battery of histone modifications (H3ac, H4ac, H4K5ac, H3K9ac, H3K27ac, H3K4me3, H3K36me2, H3K9me3, H3K27me3, and gammaH2AX), as well as HP1alpha and lamin A. We find that fully reprogrammed iPSCs are epigenetically identical to ESCs, and that partially reprogrammed iPSCs are closer to MEFs. Intriguingly, combining both time-course reprogramming experiments and data from the partially reprogrammed iPSCs, we find that heterochromatin reorganization precedes Nanog expression and active histone marking. Together, these data delineate the global epigenetic state of iPSCs in conjunction with their pluripotent state, and demonstrate that heterochromatin precedes euchromatin in reorganization during reprogramming. PMID- 22044881 TI - Exon-centric regulation of pyruvate kinase M alternative splicing via mutually exclusive exons. AB - Alternative splicing of the pyruvate kinase M gene (PK-M) can generate the M2 isoform and promote aerobic glycolysis and tumor growth. However, the cancer specific alternative splicing regulation of PK-M is not completely understood. Here, we demonstrate that PK-M is regulated by reciprocal effects on the mutually exclusive exons 9 and 10, such that exon 9 is repressed and exon 10 is activated in cancer cells. Strikingly, exonic, rather than intronic, cis-elements are key determinants of PK-M splicing isoform ratios. Using a systematic sub-exonic duplication approach, we identify a potent exonic splicing enhancer in exon 10, which differs from its homologous counterpart in exon 9 by only two nucleotides. We identify SRSF3 as one of the cognate factors, and show that this serine/arginine-rich protein activates exon 10 and mediates changes in glucose metabolism. These findings provide mechanistic insights into the complex regulation of alternative splicing of a key regulator of the Warburg effect, and also have implications for other genes with a similar pattern of alternative splicing. PMID- 22044882 TI - Sputum smear negative pulmonary tuberculosis: sensitivity and specificity of diagnostic algorithm. AB - BACKGROUND: The diagnosis of pulmonary tuberculosis in patients with Human Immunodeficiency Virus (HIV) is complicated by the increased presence of sputum smear negative tuberculosis. Diagnosis of smear negative pulmonary tuberculosis is made by an algorithm recommended by the National Tuberculosis and Leprosy Programme that uses symptoms, signs and laboratory results.The objective of this study is to determine the sensitivity and specificity of the tuberculosis treatment algorithm used for the diagnosis of sputum smear negative pulmonary tuberculosis. METHODS: A cross-section study with prospective enrollment of patients was conducted in Dar-es-Salaam Tanzania. For patients with sputum smear negative, sputum was sent for culture. All consenting recruited patients were counseled and tested for HIV. Patients were evaluated using the National Tuberculosis and Leprosy Programme guidelines and those fulfilling the criteria of having active pulmonary tuberculosis were started on anti tuberculosis therapy. Remaining patients were provided appropriate therapy. A chest X-ray, mantoux test, and Full Blood Picture were done for each patient. The sensitivity and specificity of the recommended algorithm was calculated. Predictors of sputum culture positive were determined using multivariate analysis. RESULTS: During the study, 467 subjects were enrolled. Of those, 318 (68.1%) were HIV positive, 127 (27.2%) had sputum culture positive for Mycobacteria Tuberculosis, of whom 66 (51.9%) were correctly treated with anti-Tuberculosis drugs and 61 (48.1%) were missed and did not get anti-Tuberculosis drugs. Of the 286 subjects with sputum culture negative, 107 (37.4%) were incorrectly treated with anti-Tuberculosis drugs. The diagnostic algorithm for smear negative pulmonary tuberculosis had a sensitivity and specificity of 38.1% and 74.5% respectively. The presence of a dry cough, a high respiratory rate, a low eosinophil count, a mixed type of anaemia and presence of a cavity were found to be predictive of smear negative but culture positive pulmonary tuberculosis. CONCLUSION: The current practices of establishing pulmonary tuberculosis diagnosis are not sensitive and specific enough to establish the diagnosis of Acid Fast Bacilli smear negative pulmonary tuberculosis and over treat people with no pulmonary tuberculosis. PMID- 22044883 TI - Ectodomain structures of Eph receptors. AB - Eph receptors, the largest subfamily of receptor tyrosine kinases (RTKs), and their ephrin ligands are important mediators of cell-cell communication that regulate axon guidance, long-term potentiation, and stem cell development, among others. By now, many Eph receptors and ephrins have also been found to play important roles in the progression of cancer. Since both the receptor and the ligand are membrane-bound, their interaction leads to the multimerization of both molecules to distinct clusters within their respective plasma membranes, resulting in the formation of discrete signaling centers. In addition, and unique to Eph receptors and ephrins, their interaction initiates bi-directional signaling cascades where information is transduced in the direction of both the receptor- and the ligand-bearing cells. The Ephs and the ephrins are divided into two subclasses, A and B, based on their affinities for each other and on sequence conservation. Crystal structures and other biophysical studies have indicated that isolated extracellular Eph and ephrin domains initially form high-affinity heterodimers around a hydrophobic loop of the ligand that is buried in a hydrophobic pocket on the surface of the receptor. The dimers can then further arrange by weaker interactions into higher-order Eph/ephrin clusters observed in vivo at the sites of cell-cell contact. Although the hetero-dimerization is a universal way to initiate signaling, other extracellular domains of Ephs are involved in the formation of higher-order clusters. The structures also show important differences defining the unique partner preferences of the two ligand and receptor subclasses, namely, how subclass specificity is determined both by individual interacting residues and by the precise architectural arrangement of ligands and receptors within the complexes. PMID- 22044884 TI - Ephrin reverse signaling in axon guidance and synaptogenesis. AB - Axon-cell and axon-dendrite contact is a highly regulated process necessary for the formation of precise neural circuits and a functional neural network. Eph ephrin interacting molecules on the membranes of axon nerve terminals and target dendrites act as bidirectional ligands/receptors to transduce signals into both the Eph-expressing and ephrin-expressing cells to regulate cytoskeletal dynamics. In particular, recent evidence indicates that ephrin reverse signal transduction events are important in controlling both axonal and dendritic elaborations of neurons in the developing nervous system. Here we review how ephrin reverse signals are transduced into neurons to control maturation of axonal pre-synaptic and dendritic post-synaptic structures. PMID- 22044885 TI - Targeting Eph receptors with peptides and small molecules: progress and challenges. AB - The Eph receptors are a large family of receptor tyrosine kinases. Their kinase activity and downstream signaling ability are stimulated by the binding of cell surface-associated ligands, the ephrins. The ensuing signals are bidirectional because the ephrins can also transduce signals (known as reverse signals) following their interaction with Eph receptors. The ephrin-binding pocket in the extracellular N-terminal domain of the Eph receptors and the ATP-binding pocket in the intracellular kinase domain represent potential binding sites for peptides and small molecules. Indeed, a number of peptides and chemical compounds that target Eph receptors and inhibit ephrin binding or kinase activity have been identified. These molecules show promise as probes to study Eph receptor/ephrin biology, as lead compounds for drug development, and as targeting agents to deliver drugs or imaging agents to tumors. Current challenges are to find (1) small molecules that inhibit Eph receptor-ephrin interactions with high binding affinity and good lead-like properties and (2) selective kinase inhibitors that preferentially target the Eph receptor family or subsets of Eph receptors. Strategies that could also be explored include targeting additional Eph receptor interfaces and the ephrin ligands. PMID- 22044887 TI - Poor repertoire General Movements predict some aspects of development outcome at 2 years in very preterm infants. AB - BACKGROUND: Observation of the quality of endogenously generated "General Movements" has been proved to be a reliable and sensitive tool in the assessment of fragile neonates. The absence of fidgety movements at 2-4 months post-term is highly predictive of Cerebral Palsy. On the contrary, the presence of a poor repertoire pattern during the writhing period is not reliable in predicting motor or neurobehavioral disorders at any stage of development. AIM: To examine if the presence of a PR pattern at 1 month post-term was associated with lower neurodevelopmental quotients at 2 years. STUDY DESIGN: General Movements evaluation at 1 and 3 months and the Griffiths Scales of Mental Development at 2 years were administered to a sample of very preterm infants. Infants were divided into two groups: poor repertoire pattern group and normal pattern group. Student's t Test and Chi squared test and ANOVA were used to compare neonatal variables and results between the two groups. SUBJECTS: 79 very preterm infants (birthweight<=1500 g or gestational age<=32 weeks), born January 2003 to December 2006 who had a follow-up at 2 years. OUTCOME MEASURE: Griffiths developmental quotient at 2 years. RESULTS: The Poor Repertoire group had lower Gestational Age, lower Birth Weight, lower Apgar scores at birth and lower Developmental Quotient at 2 years. Eye and Hand Coordination (subscale D) was the domain mostly responsible for such a difference. Quality of fidgety movements (normal or abnormal fidgety) at 3 months did not show any correlation with outcome measures at 2 years. CONCLUSION: The presence of a PR pattern at 1 month post-term seems to predict lower neurodevelopmental scores at 2 years especially in the domain of eye and hand coordination. Longer follow-up is necessary in order to ascertain if such difference will continue to persist at older ages. PMID- 22044886 TI - Eph and ephrin signaling in the formation of topographic maps. AB - The axonal connections between the retina and its midbrain target, the superior colliculus (SC), is mapped topographically, such that the spatial relationships of cell bodies in the retina are maintained when terminating in the SC. Topographic map development uses a Cartesian mapping system such that each axis of the retina is mapped independently. Along the nasal-temporal mapping axis, EphAs and ephrin-As, are graded molecular cues required for topographic mapping while the dorsal-ventral axis is mapped in part via EphB and ephrin-Bs. Because both Ephs and ephrins are cell surface molecules they can signal in the forward and reverse directions. Eph/ephrin signaling leads to changes in cytoskeletal dynamics that lead to actin depolymerization and endocytosis guiding axons via attraction and repulsion. PMID- 22044888 TI - Animal studies of the effects of early nutrition on long-term health. AB - Small size at birth is associated with increased risk of a variety of common chronic diseases in adulthood. Numerous experimental studies in animals have supported the observations in humans, demonstrating that changes in nutrition in early life can lead to altered long-term health. Importantly, these effects can be independent of size at birth, and can depend on the interaction between nutritional events before and after birth. Both macro- and micronutrient intake are important. Furthermore, these effects may vary according to the nature, timing, severity and duration of the nutritional insult. This review provides examples from animal studies of evidence of these long-term effects, and some possible underlying mechanisms whereby nutrition in early life can affect long term health. PMID- 22044889 TI - Dietary lipid quality and long-term outcome. AB - Understanding the importance of dietary fat has grown beyond energy metabolism to recognition of the complex roles of fatty acids, particularly the omega-6 and omega-3 fatty acids in membrane lipids, inter- and intracellular communication and in regulating gene expression. The omega-6 and omega-3 fatty acids accumulated in developing tissues depend on the fatty acids transported across the placenta and secreted in breast milk. These in turn are dependent on maternal fatty acid intakes, which have changed dramatically in the past century with current western diets high in omega-6 linoleic acid and low in omega-3 fatty acids. High intakes of omega-6 fatty acid and low intakes of omega-3 fatty acids compromise long-chain omega-3 fatty acid accumulation in tissues, and this is avoided by dietary docosahexaenoic acid. In addition to the well-known roles in neural development, newer studies are beginning to question the importance of omega-3 fatty acids as a contributor of metabolic development in other organs, with possible implications for the development of feeding behavior and integration of the nutrient energy supply. PMID- 22044890 TI - How proteins improve the development of preterm infants. AB - Amino acids and proteins play a pivotal role during growth and development. Besides acting as building blocks during tissue synthesis, amino acids or proteins act specifically by upregulating defense systems or by stimulating key sites in metabolic pathways. Following premature birth, the neonatologist is responsible for delivering the right amount and quality of nutrients to the neonate, while exact requirements are largely unknown. However, nutrition matters, both in quantity as well in quality, especially during the first few weeks and months of life. It is increasingly recognized that proteins and amino acids in the immediate postnatal phase have both short- and long-term influence on later life. PMID- 22044891 TI - The knowns and unknowns of human milk banking. AB - The provision of donor human milk instead of formula is an important contribution to the nutrition and protection from infections for preterm infants. Systematic reviews suggest a lower risk of necrotizing enterocolitis with pasteurized donor human milk (PDHM) as opposed to artificial formula, although evidence supporting PDHM use from randomized control trials is limited. Human milk banks (HMBs) must have a risk management system to maintain a safe product especially as many operate in an unregulated environment. To ensure safety, the HMB in Australia has committed to meet the appropriate standards recommended in the Code of Good Manufacturing Practices (Blood and Tissues) and models risk management during processing on Codex HACCP (Hazard Analysis Critical Control Point) requirements. There is scope to continually reevaluate the screening of donors and quality standards recommended during HMB. This will be most effective if strong networks of HMBs are developed with regional reference laboratories to encourage compliance with safety guidelines. Further research and development is needed to refine technology for treating donor milk such as thermal ultrasound and ultraviolet light, aimed at the retention of full bioactivity. HMB networks will facilitate collection of evidence for refining HMB practice which should translate to improved outcomes for preterm and sick infants. Cost effectiveness is most likely when HMBs are associated with large neonatal intensive care units. PMID- 22044892 TI - Short- and long-term effects of probiotics administered early in life. AB - The concept of manipulating the gut microbiota through the administration of probiotics during early life in order to reduce the risk of and prevent or treat diseases, including those that manifest in later life, is appealing. However, a cautious approach is needed, and the long-term consequences of such administration should be carefully evaluated. Concerns related to the early administration of probiotics include timing, i.e. the administration often begins in early infancy, sometimes at birth, when gut microbiota is not fully established, and duration, i.e. the daily administration of such products is prolonged (several weeks or months). In the case of non-breastfed infants, delivery may be in the form of a specific matrix (infant formula) that could be the only source of feeding of an infant over a prolonged period. Finally, the fact that beneficial as well as some detrimental effects are seen years after administration of probiotics during the first months of life raises concern that other long-term effects such as immunosuppression in later life may also occur. Currently, while some promising data exist, there are still more questions than answers. However, rapid progress in this area of research is expected and no doubt will bring about a number of exciting findings. PMID- 22044893 TI - New findings from the Feeding Infants and Toddlers Study 2008. AB - The purpose of this chapter is to describe the infant feeding practices among infants and toddlers (aged 0-24 months) and to describe food group consumption patterns of these infants and young children (0-48 months) participating in the 2008 Feeding Infants and Toddlers Study (FITS). The FITS 2008 is a cross sectional survey of a national sample of US children (n = 3,273). Results indicate a longer duration of breastfeeding; however, 17% of infants received cow's milk before the recommended age of one year. Introduction of complementary foods also appears to be delayed until about 4-6 months. There was a decline in consumption of infant cereal after 8 months that may be contributing to iron deficiencies in the 9-11 months age group. Consumption of 100% juice (particularly among infants) and the daily consumption of desserts or candy, sweetened beverages (particularly among 12-to 20-month-olds), and salty snacks is lower than in the 2002 survey. Overall, 10-20 and 30% of children were not consuming any fruit or vegetable, respectively, in a given day. More preschoolers were drinking 2% milk than whole milk, but about one third were still drinking whole milk. Despite some of these positive changes, improvements in young children's diet still are needed. PMID- 22044894 TI - Weaning practices in other parts of the world: case study India. AB - Infant feeding and weaning practices in India continue to demonstrate that a significant number of infants do not receive colostrum (62.8% according to the National Family Health Survey, NFHS-2), though breastfeeding is universal and continued for a longer period. In NFHS-3 (2005-2006), there is improving trend for breastfeeding within the first hour of birth (23.4%) and exclusive breastfeeding up to 5 months (46.3%); however, weaning for semisolids is delayed (55.8% only at 6-9 months of age). The infant weaning foods are inadequate in energy-protein and micronutrients. Further, weaning foods and feeding/cooking utensils are contaminated with bacteria, resulting in frequent episodes of diarrhea. Indeed, these are the factors responsible for initiation and continuation of early malnutrition which the country has failed to control as observed in the three NFHS. Over a span of 7 years, i.e. from NFHS-2 (1998-1999) to NFHS-3, there was only marginal reduction in undernutrition. Thus, uncontrolled fetal malnutrition, poor initiation of breastfeeding, inadequate and delayed weaning, and contaminated food and water demand urgency to develop affordable hygienic weaning foods, education to clean utensils, timely weaning and available potable chlorinated water to prevent and control malnutrition. PMID- 22044895 TI - Weaning practices in other parts of the world: case study Russia. AB - OBJECTIVES OF THE SURVEY: To evaluate infant feeding and weaning practices and anthropometric characteristics of 2-to 24-month-old children in Russia. SURVEY METHOD: A comprehensive analysis of data collected from face-to-face interviews of a random Russia representative sample of 2,500 mothers of children. We used a specially designed questionnaire that includes sections on health, especially feeding practices, food intake from the previous day and the measurement of height and weight. The survey was conducted within the framework of 'Start Healthy Stay Healthy' program in Russia, sponsored by Gerber, Nestle Nutrition. RESULTS: Incidence of breastfeeding among children of various age was as follows: from 2 to 4 months: 70%, from 4 to 6 months: 60%, from 6 to 9 months: 46%. The most common weaning food was fruit juice (59.4% of children), followed by fruit puree (18%) and cereals (6.4%). 4.4% of respondents used cow's milk as the first weaning food. It was found that examined children were slightly taller (z score for height-forage, 0.11) and heavier (z score for weight-for-age, 0.63) than the WHO standards. CONCLUSIONS: Evaluation of infant/toddler feeding and weaning practice will help to develop guidelines and educational programs to prevent nutrition-related diseases in Russia. PMID- 22044896 TI - Micronutrient deficiencies and effect of supplements on correcting them. AB - The etiology of micronutrient deficiencies in infancy is well described. The deficiencies are caused by one of the following four scenarios: (a) low initial stores of micronutrients from micronutrient deficiency during gestation, premature birth or low birthweight; (b) rapid postnatal growth; (c) ingestion of foods with low concentration of micronutrients, and (d) gastrointestinal pathology resulting in the malabsorption of nutrients, including micronutrients. Understanding the cause of the deficiencies is essential in planning interventions to either prevent or treat them. This chapter will focus on the dietary causes of micronutrient deficiencies and recent strategies to correct them. PMID- 22044897 TI - Food allergy and complementary feeding. AB - The relationship between complementary feeding and the development of atopic disease is the source of significant interest and debate in both the scientific and lay communities. A small number of early studies, which had considerable influence on recommended feeding practices, reported protective effects associated with delaying the introduction of commonly allergenic foods such as cow's milk, egg, and nuts. Despite more conservative recommendations, however, food allergy prevalence has continued to rise. Our understanding of the development of food allergy, its relationship with IgE sensitization and atopic dermatitis, and the relationship of each of these outcomes with the timing of food introduction has evolved considerably. Based on multiple observational studies, and extrapolating from immunotherapy trials and animal models of mucosal immunity, there is mounting evidence that delayed introduction or avoidance of commonly allergenic foods is at best neutral and may be detrimental with regard to atopic outcomes. There is an obvious and critical need for additional high caliber studies to further evaluate this connection. In the meantime, multiple health considerations, not allergy alone, should be involved in decisions regarding nutritional intake, including common allergenic foods, during the period of transition to the family diet. PMID- 22044898 TI - Early feeding: setting the stage for healthy eating habits. AB - Food habits, an integral part of all cultures, have their beginnings during early life. This chapter reviews the development of the senses of taste and smell, which provide information on the flavor of foods, and discusses how children's innate predispositions interact with early-life feeding experiences to form dietary preferences and habits. Young children show heightened preferences for foods that taste sweet and salty and rejection of that which tastes bitter. These innate responses are salient during development since they likely evolved to encourage children to ingest that which is beneficial, containing needed calories or minerals, and to reject that which is harmful. Early childhood is also characterized by plasticity, partially evidenced by a sensitive period during early life when infants exhibit heightened acceptance of the flavors experienced in amniotic fluid and breast milk. While learning also occurs with flavors found in formulae, it is likely that this sensitive period formed to facilitate acceptance of and attraction to the flavors of foods eaten by the mother. A basic understanding of the development and functioning of the chemical senses during early childhood may assist in forming evidence-based strategies to improve children's diets. PMID- 22044899 TI - Early feeding practices and development of food allergies. AB - Despite increasing efforts to prevent food allergies in children, IgE-mediated food allergies continue to rise in westernized countries. Previous preventive strategies such as prolonged exclusive breastfeeding and delayed weaning onto solid foods have more recently been called into question. The present review discusses possible risk factors and theories for the development of food allergy. An alternative hypothesis is proposed, suggesting that early cutaneous exposure to food protein through a disrupted skin barrier leads to allergic sensitization and that early oral exposure of food allergen induces tolerance. Novel interventional strategies to prevent the development of food allergies are also discussed. PMID- 22044900 TI - Learning to prefer the familiar in obesogenic environments. AB - What has become familiar tends to be preferred while the unfamiliar is avoided. Additionally, liking is impacted by associative learning processes where new stimuli become liked via repeated pairings with familiar, already-liked stimuli. In addition to the ability to learn to like new foods and flavors, infants bring genetic taste predispositions to the table, including an unlearned preference for sweet and salty tastes and a tendency to reject bitter and sour tastes. When diets were plant based, unlearned preferences for sweet and salty tastes promoted intake of foods that were relatively rare in nature but were good sources of essential nutrients; the presence of the preferred basic tastes in food no longer predicts scarce nutrients. Our 'obesogenic' dietary landscape is replete with sweet and salty foods that are energy dense, inexpensive, and exquisitely tuned to our genetic taste predispositions. In the current environment, early familiarization and associative learning can result in unhealthy diets and may promote obesity risk, but we suggest applying what we know about how food liking is learned to promote healthier diets. We review classic and current evidence demonstrating how familiarization and associative learning may be used to promote the intake of initially rejected foods like vegetables within an obesogenic context. PMID- 22044901 TI - Early feeding practices and their impact on development of celiac disease. AB - Celiac disease is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Gluten is a protein component in wheat and other cereals, including rye and barley that are generally introduced in the infant's diet at weaning. At present, two schools of thought claim that changing early feeding regimens in at-risk infants can either prevent the onset of the disease or merely delay it. Recent advances have increased our understanding of the molecular basis of this disorder and provide the rationale to perform prospective dietary interventional studies to establish the proper timing of gluten exposure to minimize the risk of developing celiac disease. PMID- 22044902 TI - Infant feeding practices and subsequent development of adipose tissue. AB - The main aspects of infant feeding that have been studied in humans in association with the subsequent development of adipose tissue include breastfeeding, rapid infancy weight gain, and weaning practices. While observational studies have consistently shown a protective effect of breastfeeding on the development of obesity, these studies may be confounded by unmeasured or unknown factors, as suggested by one study using a sibling design and one study using a randomized breastfeeding promotion intervention design. Observational studies and findings from a limited number of experimental studies suggest that rapid weight gain during infancy may be associated with an increased risk for obesity in childhood and adulthood. The association of weaning practices with later obesity has not been extensively studied, and the preliminary findings are inconsistent. Additional research studies, especially randomized interventions with long-term follow-up, are necessary in order to assess if short nutrition interventions during the critical period of infancy can have long-term benefits on the prevention of obesity. PMID- 22044903 TI - Early life nutrition and bone development in children. AB - Fetal and early life may be a critical period for the development and/or programming of metabolic systems, including the skeleton. There are increasing human data from cohort studies on the association between early life nutrition and bone development in children. Breastfed children initially have lower bone mass than bottle-fed children, but longer-term studies suggest that they have higher bone mass (size adjusted) by age 8 years, especially in children born at term. By the time of peak bone mass, both preterm and term children have higher bone mass indicating a different bone accrual trajectory curve. These children also have lower fracture risk. Diet in utero has also been associated with subsequent bone mass from ages 6 to 16 years (but not fracture). Positive associations include milk, phosphorus, magnesium, potassium, protein, folate, calcium and vitamin D, while fat intake is negative. Smoking also interferes with bone mineralization possibly due to impaired placental function, but this deleterious effect on bone mass appears to diminish over time. All of these associations are statistically significant and independent of important confounders and later environmental exposures, suggesting that osteoporosis prevention programs need to start very early in the life cycle. PMID- 22044904 TI - Igf-I signaling and effects on longevity. AB - Insulin and insulin-like signaling regulate survival and lifespan in a variety of animal species, from nematodes and flies to higher vertebrates and mammals. Recently, it was shown that brain IGF-I receptor and brain IRS2 control mammalian lifespan, and that this occurs through neuroendocrine mechanisms, control of energy metabolism and modified stress resistance. Furthermore, it was demonstrated that insulin receptor substrate molecules are implicated downstream of insulin and IGF receptors in the extension of lifespan. We showed recently that early postnatal diet plays a significant role in the development of the somatotropic axis, and that part of the neuroendocrine plasticity of growth hormone secretion depends on postnatal nutrition. We also showed that the prevalence of cardiovascular and metabolic pathologies varied with the development of somatotropic function. Neuroendocrine pathways are also prime targets for pharmacological treatments, and administration of rapamycin to adult mice has indeed recently been reported to prolong lifespan in mice. With respect to human aging, new studies identified several genes of the somatotropic axis as longevity determinants, and a recent study shows that variants of FOXO3A, downstream signaling molecule in the insulin/IGF pathway, are associated with extreme longevity in humans. Finally, several functional mutations of the human IGF-IR have been discovered in centenarians. PMID- 22044905 TI - High throughput virus plaque quantitation using a flatbed scanner. AB - The plaque assay is a standard technique for measuring influenza virus infectivity and inhibition of virus replication. Counting plaque numbers and quantifying virus infection of cells in multiwell plates quickly, accurately and automatically remain a challenge. Visual inspection relies upon experience, is subjective, often time consuming, and has less reproducibility than automated methods. In this paper, a simple, high throughput imaging-based alternative is proposed which uses a flatbed scanner and image processing software to quantify the infected cell population and plaque formation. Quantitation results were evaluated with reference to visual counting and achieved better than 80% agreement. The method was shown to be particularly advantageous in titration of the number of plaques and infected cells when influenza viruses produce a heterogeneous population of small plaques. It was also shown to be insensitive to the densities of plaques in determination of neutralization titres and IC(50)s of drug susceptibility. In comparison to other available techniques, this approach is cost-effective, relatively accurate, and readily available. PMID- 22044906 TI - Ethics in emergency medicine conferences. PMID- 22044907 TI - Digital pen and paper - introducing a new technology for prehospital data recording in German Helicopter Emergency Medical Service. PMID- 22044908 TI - Traumatic first costosternal joint subluxation complicated with occult pneumothorax: an unusual case. PMID- 22044909 TI - Physician response time when communicating with patients over the Internet. AB - BACKGROUND: Patients want to use electronic communication to access health services more easily. Health authorities in several countries see this as a way to improve health care. Physicians appear to have conflicting opinions regarding the suitability of electronic communication in clinical settings. OBJECTIVES: The aim of our study was to measure how long it actually takes physicians to answer questions from patients through an electronic communication channel, and whether some of the questions are especially time consuming. METHODS: We monitored electronic patient-physician communication. A total of 1113 messages from 14 participating physicians from 7 medical offices were analyzed. The length of questions and answers, and the time physicians spent answering the questions were recorded and analyzed. RESULTS: Physicians spent an average of 2.3 minutes (median 2 minutes) answering questions from patients. The patients' questions had an average length of 507.1 characters (95% CI 487.4-526.9, SD 336.2), while physicians' answers averaged 119.9 characters (95% CI 189.8-210.0, SD 172.6). The results show that the influence of patient question length on time spent responding was negligible. For the shortest 25% of the questions the answer time was 2.1 minutes (95% CI 1.9-2.3), while it was 2.4 minutes (95% CI 2.2-2.7) for the longest 25%. Even extremely long questions had a minimal impact on the time spent answering them. A threefold increase in question length from patients resulted in only an 18% increase in physician response time. CONCLUSIONS: The study shows the potential clinical usefulness of electronic communication between patients and health care services by demonstrating the potential for saving time. PMID- 22044910 TI - Bioinformatics analysis of rabbit haemorrhagic disease virus genome. AB - BACKGROUND: Rabbit haemorrhagic disease virus (RHDV), as the pathogeny of Rabbit haemorrhagic disease, can cause a highly infectious and often fatal disease only affecting wild and domestic rabbits. Recent researches revealed that it, as one number of the Caliciviridae, has some specialties in its genome, its reproduction and so on. RESULTS: In this report, we firstly analyzed its genome and two open reading frameworks (ORFs) from this aspect of codon usage bias. Our researches indicated that mutation pressure rather than natural is the most important determinant in RHDV with high codon bias, and the codon usage bias is nearly contrary between ORF1 and ORF2, which is maybe one of factors regulating the expression of VP60 (encoding by ORF1) and VP10 (encoding by ORF2). Furthermore, negative selective constraints on the RHDV whole genome implied that VP10 played an important role in RHDV lifecycle. CONCLUSIONS: We conjectured that VP10 might be beneficial for the replication, release or both of virus by inducing infected cell apoptosis initiate by RHDV. According to the results of the principal component analysis for ORF2 of RSCU, we firstly separated 30 RHDV into two genotypes, and the ENC values indicated ORF1 and ORF2 were independent among the evolution of RHDV. PMID- 22044911 TI - K-ras mutations in the plasma correspond to computed tomographic findings in patients with pancreatic cancer. PMID- 22044913 TI - A mixed-methods investigation to explore how women living in disadvantaged areas might be supported to improve their diets. AB - Mixed-methods explored the potential for using Sure Start Children's Centres (SSCCs) to deliver an intervention to improve the diets of disadvantaged women and their children. In an 'expert' discussion, SSCC staff described gaining women's trust, meeting needs and bringing about change as key to engaging women successfully. Structured observations in SSCCs showed they host activities in an environment conducive to building relationships and meeting women's needs. However, staff often missed opportunities to support women to make dietary changes. These data suggest that an intervention to help staff make the most of these opportunities would have the best chance of success. PMID- 22044914 TI - High levels of psychological distress in MSM are independent of HIV status. AB - This study assessed psychological distress (PD) in men who have sex with men (MSM) accessing primary health clinics in Australia. Relationships between PD, HIV status and substance use were explored. A cross-sectional convenience sample of 250 MSM completed the Personality Assessment Screener (PAS). One-third (n = 83) scored in the PAS clinically significant range, suggesting significant mental health symptoms. Negative Affect (27 per cent clinically significant), Suicidal Thinking (29 per cent clinically significant) and Amphetamine use significantly positively correlated with PD. There were no significant differences between HIV diagnostic groups on PD. A third of MSM displayed PD. Psychological screening may provide valuable information for improving the psychological well-being of MSM, regardless of their HIV status. PMID- 22044915 TI - The psychosocial determinants of the intention to reduce the number of sexual partners among recent traditionally initiated and circumcized men in the Eastern Cape Province, South Africa. AB - This study focuses on the factors associated with the intention to reduce the number of sexual partners. An individual face-to-face interview was used to collect data amongst 2337 traditionally initiated and circumcized men in the rural areas of Eastern Cape Province, South Africa. About 55.5% reported having a main sexual partner and of those 41.4% indicated having other sexual partners. The strongest association with intention was found for self-efficacy towards having one sexual partner, which accounted for almost 49% of the variance. These findings provide specific information for the development of a focused cultural sensitive STI/HIV prevention programme in sexually active young men, which can be integrated into the initiation and health education practices. PMID- 22044916 TI - Interleukin-6 impairs chronotropic responsiveness to cholinergic stimulation and decreases heart rate variability in mice. AB - Heart rate variability is reduced in several clinical settings associated with systemic inflammation. The underlying mechanism of decreased heart rate variability during systemic inflammation is unknown. It appears that the inflammatory cytokines might play a role, since epidemiologic studies has shown that circulating levels of interleukine-6 (IL-6) correlate significantly with indexes of depressed heart rate variability in various clinical conditions. The present investigation was carried out to study the peripheral and central effects of IL-6 on heart rate dynamic in mice. Adult male BALB/c mice were used in the study. RT-PCR was performed to study the expression of IL-6 receptor in mouse atrial and the results showed that gp130 mRNA was detectable in the atrium. The effect of IL-6 was also studies on chronotropic responsiveness of isolated atria to adrenergic and cholinergic stimulations. Incubation of isolated atria with 10 ng/ml of IL-6 was associated with a significant hypo-responsiveness to cholinergic stimulation (log IC50 of carbacholine changed from -6.26+/-0.10 in controls to -5.59+/-0.19 following incubation with IL-6, P<0.05). The chronotropic responsiveness to adrenergic stimulation was identical with or without incubation with IL-6. Intraperitoneal injection of IL-6 (200 ng/mouse) was associated with a significant decrease in heart rate variability parameters (SDNN, SD1, and SD2). While intracerebroventricular injection of IL-6 (50 ng/mouse) had no significant effect on heart rate variability parameters. These data are in line with a peripheral role for IL-6 in the genesis of decreased heart rate variability during systemic inflammation. PMID- 22044917 TI - Spinal anesthesia with diphenhydramine and pheniramine in rats. AB - The aim of this study was to evaluate the local anesthetic effects of pheniramine and diphenhydramine, two histamine H1 receptor antagonists, on spinal anesthesia and their comparison with lidocaine, a commonly used local anesthetic. After rats were injected intrathecally with diphenhydramine and pheniramine, the dose response curves were obtained. The potency and duration of diphenhydramine and pheniramine on spinal anesthesia were compared with lidocaine. We showed that diphenhydramine and pheniramine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50) basis, the rank of potency of drugs was diphenhydramine=pheniramine>lidocaine (p<0.05 for the differences). In equianesthetic doses (ED25, ED50, and ED75), the block duration caused by diphenhydramine was longer than that caused by pheniramine or lidocaine (p<0.01 for the differences). Diphenhydramine, but not pheniramine or lidocaine, elicited longer duration of sensory block than that of motor block at the same dose of 1.75 MUmol. These preclinical data reported that diphenhydramine with a more sensory-selective action over motor blockade demonstrated more potent and longer-lasting spinal blockades, compared with pheniramine or lidocaine. PMID- 22044918 TI - Effects of phenothiazine-class antipsychotics on the function of alpha7-nicotinic acetylcholine receptors. AB - The effects of phenothiazine-class antipsychotics (chlorpromazine, fluphenazine, phenothiazine, promazine, thioridazine, and triflupromazine) upon the function of the cloned alpha7 subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes were tested using the two-electrode voltage-clamp technique. Fluphenazine, thioridazine, triflupromazine, chlorpromazine, and promazine reversibly inhibited acetylcholine (100 MUM)-induced currents with IC50 values of 3.8; 5.8; 6.1; 10.6 and 18.3 MUM, respectively. Unsubstituted phenothiazine did not have a significant effect up to a concentration of 30 MUM. Inhibition was further characterized using fluphenazine, the strongest inhibitor. The effect of fluphenazine was not dependent on the membrane potential. Fluphenazine (10 MUM) did not affect the activity of endogenous Ca2+-dependent Cl- channels, since the extent of inhibition by fluphenazine was unaltered by intracellular injection of the Ca2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing 2 mM Ba2+. Inhibition by fluphenazine, but not by chlorpromazine was reversed by increasing acetylcholine concentrations. Furthermore, specific binding of [125I] alpha-bungarotoxin, a radioligand selective for alpha7-nicotinic acetylcholine receptor, was inhibited by fluphenazine (10 MUM), but not by chlorpromazine in oocyte membranes. In hippocampal slices, epibatidine-evoked [3H] norepinephrine release was also inhibited by fluphenazine (10 MUM) and chlorpromazine (10 MUM). Our results indicate that phenothiazine-class typical antipsychotics inhibit, with varying potencies, the function of alpha7-nicotinic acetylcholine receptor. PMID- 22044919 TI - Resveratrol inhibits interleukin 1beta-mediated inducible nitric oxide synthase expression in articular chondrocytes by activating SIRT1 and thereby suppressing nuclear factor-kappaB activity. AB - In chondrocytes, resveratrol, a natural SIRT1 activator, exerts an anti inflammatory response via inhibition of nuclear factor kappaB (NF-kappaB). Given that SIRT1 inhibits the transactivation potential of NF-kappaB by deacetylating acetylated lysines in p65, the NF-kappaB subunit, we investigated the effects of resveratrol-activated SIRT1 on articular chondrocytes. We found that when chondrocytes were stimulated with interleukin 1beta (IL-1beta), the time- and dose-dependent expression of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production was suppressed by resveratrol. Resveratrol activated SIRT1 mediated this suppression. SIRT1 suppressed not only the nuclear translocation of NF-kappaB but also the acetylation of p65. Furthermore, acetylated Lys310 in p65, which must be present for transactivation activity, was the immediate downstream target of SIRT1. Therefore, SIRT1 protects against the inflammatory response induced by IL-1beta in articular chondrocytes. Resveratrol, as an activator of SIRT1, merits consideration as a therapeutic agent in the treatment and prevention of osteoarthritis. PMID- 22044920 TI - Regulatory role of the dopamine and norepinephrine transporters in pentylenetetrazol-kindled mice: association with effect of antidepressants. AB - In clinical practice, patients with epilepsy are frequently associated with psychiatric disorders, including cognitive impairment, depression, and attention deficit hyperactivity disorder. In fact, patients with epilepsy often take centrally acting drugs, such as antidepressants and anxiolytics; however, it remains unclear whether epilepsy is associated with psychiatric function. The present study examined the effect of kindled epileptic seizures on depression like behavior in mice. The immobility time of pentylenetetrazol-kindled mice was as long as the immobility time of the controls in both a forced swimming test and a tail suspension test. Bupropion (10mg/kg, i.p.) decreased the duration of immobility in the forced swimming test of pentylenetetrazol-kindled mice, while having no significant effect in controls. Furthermore, atomoxetine (2mg/kg, i.p.) caused a significant decrease in the duration of immobility in the tail suspension test of the pentylenetetrazol-kindled mice, while having no significant effect in controls. Using immunohistochemistry, it was shown that there was no significant change in dopamine transporter levels in the striatum; however, norepinephrine transporter was significantly increased in the perirhinal cortex of the pentylenetetrazol-kindled mice. These results suggested that bupropion (in low doses) and atomoxetine are good candidates for the treatment of patients with epilepsy who suffer from psychiatric symptoms. Furthermore, this mechanism may be involved in the change of norepinephrine transporter expression, at least in the perirhinal cortex. PMID- 22044921 TI - Brazilin inhibits UVB-induced MMP-1/3 expressions and secretions by suppressing the NF-kappaB pathway in human dermal fibroblasts. AB - Brazilin (7, 11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10 (6H)-tetrol), the major component of Caesalpinia sappan L., is a natural red pigment used for histological staining. Recent studies have shown that brazilin exhibits distinct biological effects, including anti-hepatotoxicity, antiplatelet activity, and anti-inflammatory activities. In the present study, we evaluated the effects of brazilin on MMP-1 and -3 expressions in human dermal fibroblasts exposed to ultraviolet B (UVB) irradiation. Brazilin showed protective effect on UVB-induced loss of cell viability of fibroblasts. Brazilin also blocked significantly UVB induced Reactive Oxygen Species generation in fibroblasts. Brazilin inhibited UVB induced MMP-1/3 expressions and secretions in a dose-dependent manner. Moreover, UVB-induced NF-kappaB activation was completely blocked by treatment with brazilin. These findings suggest that brazilin inhibits UVB-induced MMP-1/3 expressions and secretions by suppressing of NF-kappaB activation in human dermal fibroblasts. Thus, brazilin might be used as a potential agent for treatment of UV-induced skin photoaging. PMID- 22044922 TI - Brain-derived neurotrophic factor-activated astrocytes produce mechanical allodynia in neuropathic pain. AB - Neuropathic pain management is challenging for physicians and a vexing problem for basic researchers. Recent studies reveal that activated spinal astrocytes may play a vital role in nerve injury-induced neuropathic pain, although the mechanisms are not fully understood. We have found increased glial fibrillary acidic protein (GFAP) expression, a hallmark of reactive gliosis, and elevated brain-derived neurotrophic factor (BDNF) expression in the dorsal horn in a rat model of allodynia induced by spinal nerve ligation (SNL). The high GFAP expression and mechanical allodynia that SNL induces were prevented by the intrathecal injection of the BDNF-sequestering fusion protein TrkB/Fc. Additionally, mechanical allodynia and GFAP overexpression was induced by the spinal administration of exogenous BDNF to naive rats, and exogenous BDNF given together with fluorocitrate, an astrocytic metabolism inhibitor, inhibited allodynia and GFAP upregulation. Exogenous BDNF also activated the astrocytes directly when tested in vitro. Furthermore, intrathecal administration of BDNF stimulated astrocytes also induced mechanical allodynia in naive rats. All of these results indicate that astrocytes activated by BDNF might contribute to mechanical allodynia development in neuropathic pain in rats. PMID- 22044923 TI - Intrinsically photosensitive ganglion cells of the primate retina express distinct combinations of inhibitory neurotransmitter receptors. AB - Intrinsically-photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and function as irradiance detectors, responsible for crucial non-image forming visual functions. In addition to their intrinsic photosensitivity, ipRGCs are also activated by synaptic inputs originating at the classical photoreceptors, rods and cones. Little is known about inhibition through these retinal pathways, despite ipRGCs receiving massive synaptic inputs from inhibitory amacrine interneurons. We performed a wide anatomical screening for neurotransmitter receptors possibly involved in the inhibitory modulation of ipRGCs in the macaque retina. We investigated both subtypes of primate ipRGCs described so far and report that outer-stratifying (M1) cells possess mainly GlyR alpha2 and GABA(A)R alpha3 subunits, while inner-stratifying (M2) cells are overall subject to less inhibitory modulation. Our results suggest that M1 and M2 ipRGC subtypes are modulated via distinct inhibitory intraretinal circuits. PMID- 22044924 TI - Monaural conductive hearing loss alters the expression of the GluA3 AMPA and glycine receptor alpha1 subunits in bushy and fusiform cells of the cochlear nucleus. AB - The impact of conductive hearing loss (CHL), the second most common form of hearing loss, on neuronal plasticity in the central auditory pathway is unknown. After short-term (1 day) monaural earplugging, the GluA3 subunits of the AMPA receptor (AMPAR) are upregulated at auditory nerve synapses on the projection neurons of the cochlear nucleus; glycine receptor alpha1 (GlyRalpha1) subunits are downregulated at inhibitory synapses in the same neuronal population. These data suggest that CHL affects receptor trafficking at synapses. We examined the impact of 7 days of CHL on the general expression of excitatory and inhibitory receptors by quantitative biochemistry and immunohistochemistry, using specific antibodies to detect AMPAR subunits (GluA1, GluA2, GluA2/3, and GluA4), GlyRalpha1, and the GABA(A) receptor subunits beta2/3. Following monaural earplugging and an elevation of the hearing threshold by approximately 35 dB, the immunolabeling of the antibody for the GluA2/3 subunits but not the GluA2 subunit increased on bushy cells (BCs) and fusiform cells (FCs) of the ipsilateral ventral and dorsal cochlear nuclei. These same cell types showed a downregulation of the GlyRalpha1 subunit. Similar results were observed in the contralateral nuclei. The expression levels of GABA(A) beta2/3 were unchanged. These findings suggest that, following longer periods of monaural conductive hearing loss, the synthesis and subsequent composition of specific glutamate and glycine receptors in projection neurons and their synapses are altered; these changes may contribute to abnormal auditory processing. PMID- 22044925 TI - Predictors of adipose tissue concentrations of organochlorine pesticides in a general Danish population. AB - Organochlorine pesticides are ubiquitously present in the environment and suspected of carcinogenic, neurological and immunological effects. Our objective was to identify determinants of adipose tissue levels of organochlorine pesticides experienced by a general Danish population. Adipose tissue was collected upon enrolment of 245 randomly selected persons from a prospective cohort of 57,053 persons enrolled between 1993 and 1997. We examined geography, gender, age, lactation, body mass index (BMI) and intake of nine dietary groups and tap water drinks, as potential determinants of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene, hexachlorocyclohexane, dieldrin, hexachlorobenzene, cis-nonachlor, trans nonachlor and oxychlordane. Living in Copenhagen city and age at enrolment showed positive associations with all compounds. BMI was positively associated with all compounds except cis-nonachlor. Fatty-fish consumption showed positive associations with cis-nonachlor, trans-nonachlor, DDT and dieldrin and fruit and vegetables were inversely associated with dieldrin. Determinant estimates of trans-nonachlor were similar to estimates of total chlordanes while cis-nonachlor and oxychlordane seemed to differ. This is one of the first studies of organochlorine pesticides predictors in adipose tissue and contributes to the ongoing debate about exposure sources of these compounds. Single determinants varied among the individual compounds, even within related chlordane residues, suggesting that organochlorine pesticides should not be treated as a homogenous group. PMID- 22044926 TI - Urinary biomarkers of occupational jet fuel exposure among Air Force personnel. AB - There is a potential for widespread occupational exposure to jet fuel among military and civilian personnel. Urinary metabolites of naphthalene have been suggested for use as short-term biomarkers of exposure to jet fuel (jet propulsion fuel 8 (JP8)). In this study, urinary biomarkers of JP8 were evaluated among US Air Force personnel. Personnel (n=24) were divided a priori into high, moderate, and low exposure groups. Pre- and post-shift urine samples were collected from each worker over three workdays and analyzed for metabolites of naphthalene (1- and 2-naphthol). Questionnaires and breathing-zone naphthalene samples were collected from each worker during the same workdays. Linear mixed effects models were used to evaluate the exposure data. Post-shift levels of 1- and 2-naphthol varied significantly by a priori exposure group (levels in high group>moderate group>low group), and breathing-zone naphthalene was a significant predictor of post-shift levels of 1- and 2-naphthol, indicating that for every unit increase in breathing-zone naphthalene, there was an increase in naphthol levels. These results indicate that post-shift levels of urinary 1- and 2 naphthol reflect JP8 exposure during the work-shift and may be useful surrogates of JP8 exposure. Among the high exposed workers, significant job-related predictors of post-shift levels of 1- and 2-naphthol included entering the fuel tank, repairing leaks, direct skin contact with JP8, and not wearing gloves during the work-shift. The job-related predictors of 1- and 2-naphthol emphasize the importance of reducing inhalation and dermal exposure through the use of personal protective equipment while working in an environment with JP8. PMID- 22044927 TI - Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays. AB - AIMS: We sought to examine the diagnostic and prognostic utility of sensitive cardiac troponin (cTn) assays in patients with pre-existing coronary artery disease (CAD). METHODS AND RESULTS: We conducted a multicentre study to examine the diagnostic accuracy of one high-sensitive and two sensitive cTn assays in 1098 consecutive patients presenting with symptoms suggestive of acute myocardial infarction (AMI), of whom 401 (37%) had pre-existing CAD. Measurements of Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, Abbott-Architect cTnI and the standard assay (Roche cTnT) were performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the final diagnosis in 19% of CAD patients. Among patients with diagnoses other than AMI, baseline cTn levels were elevated above the 99th percentile with Roche hs-cTnT in 40%, with Siemens TnI-Ultra in 15%, and Abbott Architect cTnI in 13% of them. In patients with pre-existing CAD, the diagnostic accuracy at presentation, quantified by the area under the receiver operator characteristic curve (AUC), was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.92; Siemens cTnI-Ultra, 0.94; and Abbott-Architect cTnI, 0.93 vs. AUC for the standard assay, 0.87; P < 0.01 for all comparisons). Elevated levels of cTn measured with the sensitive assays predicted mortality irrespective of pre-existing CAD, age, sex, and cardiovascular risk factors. CONCLUSION: Sensitive cTn assays have high diagnostic accuracy also in CAD patients. Mild elevations are common in non-AMI patients and test-specific optimal cut-off levels tend to be higher in CAD patients than in patients without history of CAD. Sensitive cTn assays also retain prognostic value. (ClinicalTrials.gov number, NCT00470587). PMID- 22044928 TI - High temperatures and cause-specific mortality. PMID- 22044929 TI - The hydrazide/hydrazone click reaction as a biomolecule labeling strategy for M(CO)3 (M = Re, (99m)Tc) radiopharmaceuticals. AB - Facile reactivity of hydrazides and aldehydes was explored as potential coupling partners for incorporation into M(CO)(3) (M = Re, (99m)Tc) based radiopharmaceuticals. Both 'click, then chelate' and 'prelabel, then click' synthetic routes produced identical products in high yields and lacked metal hydrazide/-hydrazone interactions, highlighting the potential of this click strategy. PMID- 22044931 TI - Delivered oxygen fraction during simulated cardiopulmonary resuscitation depending on the kind of resuscitation bag and oxygen flow. AB - Emergency cases for resuscitation include built-in oxygen cylinders with limited oxygen supply. The use of a bag-valve mask device (BVMD) with a reservoir requires a high constant flow of oxygen to maintain a high concentration of delivered oxygen. The goal of the study was to analyze what fraction of inspired oxygen (FiO2) can be reached and how long it takes using different BVMD with their reservoir device and different oxygen flows in order to allow a reduction in oxygen requirements during simulated cardiopulmonary resuscitation (CPR). Experimental analysis was carried out during simulated CPR on the effect in the final FiO2 and the time required to reach it using two different models of BVMD with their reservoir device: Mark IV and Revivator-Plus and four different oxygen flows 5, 10, 15, and 10 l/min during 1 min, followed by 5 l/min (10-5). With both the BVMDs studied, the FiO2 values reached at 10, 15, and 10-5 l/min were higher than 0.85 [Mark IV=0.87 (0.01); Revivator=0.93 (0.03)] in 60 s. At 5 l/min FiO2 were lower in 60 s (P<0.001) and were higher than 0.85 [Mark IV=0.90 (0.005); Revivator=0.90 (0.005)] in 80 s. The mean FiO2 was lower with the Mark IV (P<0.05) (Table 1). To allow a substantial reduction in oxygen requirements, a 10 l/min for 1 min, followed by 5 l/min of oxygen flow can be used during CPR with both BVMDs studied. Increasing supplemental oxygen flow did not appreciably increase the FiO2. PMID- 22044932 TI - Horizontal subxiphoid landmark optimizes probe placement during the Focused Assessment with Sonography for Trauma ultrasound exam. AB - OBJECTIVE: To introduce an external landmark for optimizing probe placement during Focused Assessment with Sonography for Trauma (FAST) exam. METHODS: This prospective study was conducted in two phases. First, the students and emergency medicine residents were trained in FAST exam utilizing the horizontal subxiphoid (HS) landmark. The landmark consists of the crossing points of a horizontal line extending from the xiphoid process to the right midaxillary line (H point) and left posterior axillary line (S point). Second, the trained students and residents performed FAST among Emergency Departments patients at two teaching hospitals. The primary outcome was a target organ acquisition score for each view, derived from the number of target organs visualized on an initial probe placement. Secondary endpoints included: time required to obtain the requisite images, and the impact of patient characteristics on landmark prediction rate. RESULTS: Forty-eight providers performed 477 exams. The collective prediction rate of the HS landmark was 86.6% for both H and S points upon first attempt without further probe adjustments. Operators visualized all required target structures at the first probe placement site in 430 out of 477 (90.1%) cases at the right upper quadrant, and in 392 out of 474 (82.7%) cases at the left upper quadrant without further probe adjustments. Limited probe adjustment (<2 cm from the initial landmark site) improved the success rate up to 95.6 and 90% to the right upper quadrant and left upper quadrant, respectively. As BMI increased, precision score decreased and image acquisition time increased. CONCLUSION: The HS line is an external landmark that may optimize probe placement and facilitates teaching and performance of FAST examination. PMID- 22044933 TI - Verapamil results in increased blood levels of oncolytic adenovirus in treatment of patients with advanced cancer. AB - Calcium channel blockers including verapamil have been proposed to enhance release and antitumor efficacy of oncolytic adenoviruses in preclinical studies but this has not been studied in humans before. Here, we studied if verapamil leads to increased replication of oncolytic adenovirus in cancer patients, as measured by release of virions from tumor cells into the systemic circulation. The study was conducted as a matched case-control study of advanced cancer patients treated with oncolytic adenoviruses with or without verapamil. We observed that verapamil increased mean virus titers present in blood after treatment (P < 0.05). The frequency or severity of adverse events was not increased, nor were cytokine responses or neutralizing antibody levels different between groups. Signs of possible treatment-related clinical benefits were observed in both groups, but there was no significant difference in responses or survival. Thus, our data suggests that the combination of verapamil with oncolytic adenoviruses is safe and well tolerated. Moreover, verapamil treatment seems to result in higher virus titers in blood, indicating enhanced overall replication in tumors. A randomized trial is needed to confirm these findings and to study if enhanced replication results in benefits to patients. PMID- 22044934 TI - Functionally enhanced siRNA targeting TNFalpha attenuates DSS-induced colitis and TLR-mediated immunostimulation in mice. AB - Tumor necrosis factor (TNFalpha) is a proinflammatory cytokine involved in the pathogenesis of inflammatory bowel disease (IBD). Although TNFalpha has been extensively targeted using systemic drugs, the use of antisense and small interfering RNA (siRNA) to drive down its expression at the site of inflammation should provide important advantages. In this study, native and chemically modified siRNA against TNFalpha was developed and characterized using a murine model of IBD. siRNA with 2'-O-methyl and propanediol modifications (siTNF-OMe-P) were resistant to nuclease degradation and provided better silencing efficacy in vitro as compared to unmodified siRNA. Every modification reduced nonspecific Toll-like receptor (TLR)-mediated immunomodulation in human peripheral blood mononuclear cells (PBMC) cells. Intrarectal administration of siTNF-OMe-P significantly ameliorated the clinical endpoints and histopathological severity in 5% dextran sulphate sodium (DSS)-treated mice as compared to unmodified and other chemically modified siRNAs. Differential gene expression assessed in siTNF OMe-P-treated animals correlated with improved colon integrity and reduced TLR activation as compared to all treatment groups. All in all, this study demonstrates that propanediol and 2'-O-methyl modifications have profound functional consequences for siRNA efficacy in vivo. Consequently, this strategy has potential implications for therapeutic intervention in IBD and other diseases. PMID- 22044936 TI - On the origin of the alternating Diels-Alder reactivity in [n]dendralenes. AB - G4(MP2) calculations on Diels-Alder reactions of [3]- and [4]dendralene have revealed that reactant dendralene conformer populations and closed-shell singlet bis-pericyclic transition states explain their different reactivities. PMID- 22044935 TI - Correction of murine Bernard-Soulier syndrome by lentivirus-mediated gene therapy. AB - Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder caused by a defect in the platelet glycoprotein (GP) Ib-IX-V complex. The main treatment for BSS is platelet transfusion but it is often limited to severe bleeding episodes or surgical interventions due to the risk of alloimmunization. We have previously reported successful expression of human GPIbalpha (hGPIbalpha) in human megakaryocytes using a lentiviral vector (LV) encoding human GP1BA under control of the platelet-specific integrin alphaIIb promoter (2bIbalpha). In this study, we examined the efficacy of this strategy for the gene therapy of BSS using GPIbalpha(null) as a murine model of BSS. GPIbalpha(null) hematopoietic stem cells (HSC) transduced with 2bIbalpha LV were transplanted into lethally irradiated GPIbalpha(null) littermates. Therapeutic levels of hGPIbalpha expression were achieved that corrected the tail bleeding time and improved the macrothrombocytopenia. Sequential bone marrow (BM) transplants showed sustained expression of hGPIbalpha with similar phenotypic correction. Antibody response to hGPIbalpha was documented in 1 of 17 total recipient mice but was tolerated without any further treatment. These results demonstrate that lentivirus-mediated gene transfer can provide sustained phenotypic correction of murine BSS, indicating that this approach may be a promising strategy for gene therapy of BSS patients. PMID- 22044937 TI - Prostate-specific antigen testing in Tyrol, Austria: prostate cancer mortality reduction was supported by an update with mortality data up to 2008. PMID- 22044938 TI - Towards new therapeutic approaches for malignant melanoma. AB - Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology. PMID- 22044939 TI - Impact of SHMT1 polymorphism on the clinical outcome of patients with metastatic colorectal cancer treated with first-line FOLFIRI+bevacizumab. AB - The impact of thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and serine hydroxymethyltransferase 1 (SHMT1) gene polymorphisms and that of dihydropyrimidine dehydrogenase (DPD) enzyme activity, serum total homocysteine level, and estimated serum creatinine clearance on first-line 5 fluorouracil, leucovorin, irinotecan, and bevacizumab (FOLFIRI+bevacizumab) regimen efficacy in metastatic colorectal cancer patients was investigated. DNA was extracted from peripheral blood mononuclear cells. Genotyping was performed for TYMS 5'UTR variable number tandem repeat, TYMS 3'UTR ins/del, MTHFR C677T, and SHMT1 C1420T polymorphisms. The DPD activity of peripheral blood mononuclear cells was also determined. The univariate and multivariate analyses demonstrated that the SHMT1 1420T allele was associated with better response (P=0.025) and longer progression-free survival (PFS) (P=0.00004) and overall survival (OS) (P=0.034). Grade >=2 hypertension was also an independent prognostic factor of longer progression-free survival and OS. Bevacizumab-related hypertension might be a predictive marker of treatment efficacy (P=0.0002 for OS) in the case of wild (CC) SHMT1 1420 genotypes only. PMID- 22044940 TI - ADH4 intronic variations are associated with alcohol dependence: results from an Italian case-control association study. AB - OBJECTIVES: This study investigated the involvement of ADH4 gene polymorphisms in the susceptibility to alcohol use disorders. METHODS: Thirty-eight single nucleotide polymorphisms (SNPs) in and around the ADH4 gene were investigated in 136 Italian alcoholics and 276 healthy controls. A new approach based on a bioinformatic method selected 26 SNPs that may affect the splicing sites, destroying or creating binding sites of splicing regulatory proteins. RESULTS: Case-control comparisons for allele and genotype frequencies showed that ADH4 SNPs were associated with alcohol dependence but not with alcohol abuse. The association signal was strongest for rs1009145, rs13148577 (both P=0.0008) and rs7689753 (P=0.0007), whose minor alleles were predicted to alter the target protein sequences involved in mRNA splicing. A pairwise linkage disequilibrium analysis showed that all SNPs except five were located in a single haplotype block. Six haplotype tag SNPs were selected to infer haplotypes and to estimate their frequency distributions. A logistic regression analysis confirmed the association between ADH4 variants and alcohol dependence when sex, age, years of education, marital status and the allele genotype, haplotype and diplotype data of the six haplotype tag SNP were considered. Haplotype ATAAAT, which contained the minor allele of rs10009145 and the major allele of rs7689753, increased the risk of alcohol dependence, whereas haplotype GGGGAT, bearing the major allele of rs10009145 and the minor allele of rs7689753, protected against it. Again, there was no evidence of an association with alcohol abuse. CONCLUSION: These data suggest that ADH4 intronic variants play a role in alcohol dependence susceptibility in Italian populations. Functional studies are needed to establish the role of the genetic variations that seem to affect the splicing mechanism. PMID- 22044942 TI - 4-Thiothymidine sensitization of DNA to UVA offers potential for a novel photochemotherapy. AB - Photochemotherapy, in which ultraviolet radiation (UVR: 280-400 nm) or visible light is combined with a photosensitizing drug to produce a therapeutic effect that neither drug or radiation can achieve alone, is a proven therapeutic strategy for a number of non-malignant hyperproliferative skin conditions and various cancers. Examples are psoralen plus UVA (320-400 nm) radiation (PUVA) and photodynamic therapy (PDT). All existing photochemotherapies have drawbacks - for example the association of PUVA with the development of skin cancer, and pain that is often associated with PDT treatment of skin lesions. There is a clear need to develop alternative approaches that involve lower radiation doses and/or improved selectivity for target cells. In this review, we explore the possibility to address this need by exploiting thionucleoside-mediated DNA photosensitisation to low, non toxic doses of UVA radiation. PMID- 22044941 TI - Patterns of interaction between genetic and nongenetic attributes and methotrexate efficacy in rheumatoid arthritis. AB - OBJECTIVE: The contribution of low-penetrance single nucleotide polymorphisms to methotrexate efficacy in rheumatoid arthritis (RA) is inconsistent between studies. We sought to elucidate architecture of methotrexate response in three cohorts of patients with RA treated with methotrexate. METHODS: Single nucleotide polymorphism frequencies in genes from folate, purine, and pyrimidine pathways were measured to develop a model of gene-gene interactions using multifactor dimensionality reduction in 439 patients who received methotrexate in the USA and The Netherlands. A third cohort of 530 patients with RA from Sweden was used to replicate the findings. Methotrexate efficacy was assessed using the European League Against Rheumatism criteria in the majority of patients. RESULTS: Nonlinear patterns of gene-gene interactions between variants in aminoimidazole carboxamide ribonucleotide transformylase (C347G), reduced-folate carrier (G80A) and inosine-triphosphate pyrophosphatase (C94A) revealed a predisposing genetic attribute significantly associated with methotrexate response in the USA and Dutch cohorts [odds ratio (OR)=2.9, 95% confidence interval (CI): 1.9-4.2; P<0.001]. Although the finding was not replicated in the Swedish cohort (OR=0.9; 95% CI: 0.64-1.37; P=0.74) a multifactor dimensionality reduction analysis superimposing the predisposing genetic attribute with patient's age, sex, and anticitrullinated peptide antibodies positivity (ACPA) revealed a pattern of interaction significant in all three cohorts (OR=2.2, 95% CI: 1.6-2.9; P<0.01). The selective advantage toward response in the presence of the predisposing genetic attribute was lost in females and ACPA-positive patients, whereas older and male ACPA-negative patients tended to exhibit a greater likelihood of response in the absence of the predisposing genetic attribute. CONCLUSION: Gene gene interactions together with nongenetic attributes may contribute to methotrexate efficacy in RA. PMID- 22044944 TI - Role of puerarin in the signalling of neuropathic pain mediated by P2X3 receptor of dorsal root ganglion neurons. AB - Tissue injury or inflammation of the nervous system may result in chronic neuropathic pain characterized by sensitivity to painful stimuli. P2X(3) receptors play a crucial role in facilitating pain transmission. Puerarin is an active compound of a traditional Chinese medicine Ge-gen, and Ge-gen soup has anti-inflammatory effects. The present research investigated the role of puerarin in the signalling of chronic neuropathic pain mediated by P2X(3) receptors of rat dorsal root ganglion neurons. Chronic constriction injury (CCI) rat model was adopted. Sprague-Dawley rats were randomly divided into blank control group (Ctrl), sham group (Sham), puerarin-treated control group (Ctrl+PUE), chronic constriction injury (CCI) group and puerarin-treated CCI group (CCI+PUE). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by the von-Frey test and the Hargreaves' test respectively. The stain values of P2X(3) protein and mRNA in L4/L5 dorsal root ganglion (DRG) were detected by immunohistochemistry, western blot and in situ hybridization. At day 4-7 after the operation of CCI rats, MWT and TWL in group CCI and CCI+PUE were lower than those in group Ctrl, Sham and Ctrl+PUE, while there was no difference among group Ctrl, Sham and Ctrl+PUE. At day 7-10 after operation, MWT and TWL in group CCI+PUE was higher than those in group CCI, but there was no significant difference between group CCI+PUE and group Ctrl (p>0.05). At day 14 after operation, the stain values of P2X(3) proteins and mRNAs in L4/L5 DRG of group CCI were higher than those in group Ctrl, Sham, Ctrl+PUE and CCI+PUE, while the stain values of P2X(3) proteins and mRNAs in group CCI+PUE were significantly decreased compared with those in group CCI. Therefore, puerarin may alleviate neuropathic pain mediated by P2X(3) receptors in dorsal root ganglion neurons. PMID- 22044943 TI - Acute neuregulin-1 signaling influences AMPA receptor mediated responses in cultured cerebellar granule neurons. AB - Neuregulin-1 (NRG1) is a trophic and differentiation factor that signals through ErbB receptor tyrosine kinases to regulate nervous system development. Previous studies have demonstrated that NRG1 affects plasticity at glutamatergic synapses in principal glutamatergic neurons of the hippocampus and frontal cortex; however, immunohistochemical and genetic analyses strongly suggest these effects are indirect and mediated via ErbB4 receptors on GABAergic interneurons. Here, we used cultured cerebellar granule cells (CGCs) that express ErbB4 to analyze the cell-autonomous effects of NRG1 stimulation on glutamatergic function. These cultures have the advantage that they are relatively homogenous and consist primarily of granule neurons that express ErbB4. We show that acute NRG1 treatment does not affect whole-cell AMPA or NMDA receptor (NMDAR) mediated currents in CGCs at 10-12 days in vitro. NRG1 also does not affect the frequency or amplitude of spontaneous AMPAR or NMDAR mediated miniature excitatory post synaptic currents (mEPSCs). To further investigate the effects of NRG1 on activity-dependent plasticity of glutamatergic synapses in CGCs, we characterized the effects of high-glyine/0 Mg(2+) (which activates synaptic NMDARs) on AMPAR mEPSC frequency and amplitude. We show that high-glycine induces a form of chemical long-term potentiation (chemLTP) in CGCs characterized by an increase in AMPAR-mEPSC frequency but not amplitude. Moreover, NRG1 induces a decrease in AMPAR-mEPSC frequency following chemLTP, but does not affect AMPAR-mEPSC amplitude. CGCs in our cultures conditions express low levels of GluR1, in contrast to dissociated hippocampal cultures, but do express the long isoform of GluR4. This study provides first evidence that (1) high-glycine can induce plasticity at glutamatergic synapses in CGCs, and (2) that acute NRG1/ErbB signaling can regulate glutamatergic plasticity in CGCs. Taken together with previous reports, our results suggest that, similar to Schaeffer collateral to CA1 synapses, NRG1 effects are activity dependent and mediated via modulation of synaptic AMPARs. PMID- 22044946 TI - Utility of TOMM Trial 1 as an indicator of effort in children and adolescents. AB - Although measuring test compliance in a pediatric neuropsychological evaluation is important, increasing demands on clinicians' time and the need for efficiency during assessments may make it difficult to routinely include effort testing. This study investigated whether performance on Trial 1 of the Test of Memory Malingering (TOMM) is predictive of overall performance in children and adolescents with neurological disorders. Participants included 53 children and adolescents between six and 19 years (mean age = 12.4, SD = 4.1) who were followed through a neurology clinic at a tertiary care hospital. Several cutoff scores were examined, with the goal of maximizing positive predictive (accurate detection of failure on the TOMM) and negative predictive (accurate detection of passing the TOMM) values. Every participant who scored >=36 on Trial 1 (n = 50) went on to pass the TOMM. This study is the first step in providing evidence that performance on Trial 1 might be used as a quick screening measure of overall performance on the TOMM in children and adolescents. Further research on this topic is warranted. PMID- 22044947 TI - Clinical and organisational aspects of haemophilia care: the patients' view. PMID- 22044948 TI - Factor VIII inhibitor and source of replacement therapy. PMID- 22044949 TI - Blood donors' attitudes towards incentives: influence on motivation to donate. AB - BACKGROUND: Understanding the factors that motivate donors to donate will facilitate improvements in recruitment programmes. Donation incentives are often used to improve the effect of recruitment programmes. This cross-sectional study was designed to understand donors' attitudes toward incentives. MATERIAL AND METHODS: Participants (n=421) were recruited among volunteer donors at the Shiraz Blood Transfusion Centre when they registered for blood donation. They completed a questionnaire with items regarding demographic characteristics, donation status (first-time donor or regular donor), and their motivation for donating, their attitude towards incentives, and the best type of incentives. Multiple logistic regression and chi-squared tests were used to analyse the data with Statistical Package for the Social Sciences (SPSS) software. RESULTS: The majority of donors (85.6%) donated blood for altruistic reasons. One quarter of the donors (25.3%) believed that incentives should be offered to encourage them to donate. Most donors (84.5%) believed that the most effective incentive was offering specific blood tests. Donors who had donated for non-altruistic reasons were more interested in receiving incentives. The desire to receive incentives was more widespread among younger, married, first-time donors, donors with a lower educational level and donors with a history of more than five donations. The desire to receive incentives decreased as age increased. DISCUSSION: Most of the donors (74.7%) had no desire to receive incentives, and this was even more apparent among donors who donated for altruistic reasons. Non-monetary incentives may be effective in attracting younger, married, first-time donors, donors with a lower educational level and donors with a history of more than five donations. PMID- 22044950 TI - Blood conservation strategies for emergency open cardiac surgery in a patient with anti-M. PMID- 22044951 TI - Long-term persistence of molecular response after discontinuation of interferon alpha in two patients with chronic myeloid leukaemia. PMID- 22044953 TI - Dimethyl sulphoxide does not contribute to renal failure in patients undergoing stem cell transplant for multiple myeloma and primary amyloidosis. PMID- 22044952 TI - Emergency reversal of anticoagulation: from theory to real use of prothrombin complex concentrates. A retrospective Italian experience. AB - BACKGROUND: Prothrombin Complex Concentrates (PCC) are administered to normalise blood coagulation in patients receiving oral anticoagulant therapy (OAT). Rapid reversal of OAT is essential in case of major bleeding, internal haemorrhage or surgery.The primary end-point was to evaluate whether PCC in our hospital were being used in compliance with international and national guidelines for the reversal of OAT on an emergency basis. The secondary end-point was to evaluate the efficacy and safety of PCC. MATERIALS AND METHODS: All patients receiving OAT who required rapid reversal anticoagulation because they had to undergo emergency surgery or urgent invasive techniques following an overdose of oral anticoagulants were eligible for this retrospective observational study. RESULTS: Forty-seven patients receiving OAT who needed rapid reverse of anticoagulation were enrolled in our study. The patients were divided in two groups: (i) group A (n=23), patients needed haemostatic treatment before neurosurgery after a head injury and (ii) group B (n=24), patients with critical haemorrhage because of an overdose of oral anticoagulants. The International Normalised Ratio (INR) was checked before and after infusion of the PCC. The mean INR in group A was 2.7 before and 1.43 after infusion of the PCC; in group B the mean INR of 6.58, before and 1.92 after drug infusion. The use of vitamin K, fresh-frozen plasma and red blood cells was also considered. During our study 22 patients died, but no adverse effects following PCC administration were recorded. DISCUSSION: In our study three-factor-PCC was found to be effective and safe in rapidly reversing the effects of OAT, although it was not always administered in accordance with international or national guidelines. The dose, time of administration and monitoring often differed from those recommended. In the light of these findings, we advocate the use of single standard protocol to guide the correct use of PCC in each hospital ward. PMID- 22044954 TI - Autologous platelet gel for tissue regeneration in degenerative disorders of the knee. AB - BACKGROUND: The refinement of the use of platelet-derived growth factors that has occurred over the last decade has led to a broadening of the fields of use, in particular for new treatments in orthopaedics aimed at improving tissue regeneration. MATERIALS AND METHODS: Twenty-seven patients, aged between 18 and 81 years, with a diagnosis of degenerative joint disease lasting for more than 1 year were treated. The patients were divided into two groups, one with arthritis of the knee, the other with degenerative cartilage disease of the knee. Both groups were treated with a therapeutic protocol consisting of a cycle of three infiltrations of platelet-rich plasma at weekly intervals.The extemporaneous preparation was made from a sample of about 8 mL of venous whole blood collected into a specific Fibrin Polymer 2 test-tube from RegenLab((r)) and centrifuged before addition of calcium gluconate.During the initial pre-treatment evaluation, specific questionnaires were administered, the Numerical Rating Scale (NRS) for subjective measurement of pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); these assessments were repeated 7 days after the end of the treatment and at 6 months during the follow-up. RESULTS: The parameters evaluated improved in both groups after treatment and there was a further improvement after 6 months of follow-up; furthermore, there was a substantial decrease in pain right after the first infiltration. DISCUSSION: The patients were treated on an out-patient basis by a specifically created multidisciplinary team comprising a transfusion specialist, an orthopaedist and a radiologist, who collaborate in a symbiotic manner. The out-patient protocol exploits the regenerative properties of platelet-rich plasma, which is a low cost treatment; in practice, a diagnostic-therapeutic programme of lower intensity, but of high technical and professional quality is created. The strategy also reduces both the number of hospital services and the pharmacological support required, thereby optimising the use of health care resources. PMID- 22044955 TI - Reaction to the review article "Troubleshooting in platelet storage temperature and new perspectives through proteomics". PMID- 22044957 TI - Appropriateness of blood transfusion and physicians' education: a continuous challenge for Hospital Transfusion Committees? PMID- 22044958 TI - Automated processing of whole blood units: operational value and in vitro quality of final blood components. AB - BACKGROUND: The Community Transfusion Centre in Madrid currently processes whole blood using a conventional procedure (Compomat, Fresenius) followed by automated processing of buffy coats with the OrbiSac system (CaridianBCT). The Atreus 3C system (CaridianBCT) automates the production of red blood cells, plasma and an interim platelet unit from a whole blood unit. Interim platelet unit are pooled to produce a transfusable platelet unit. In this study the Atreus 3C system was evaluated and compared to the routine method with regards to product quality and operational value. MATERIALS AND METHODS: Over a 5-week period 810 whole blood units were processed using the Atreus 3C system. The attributes of the automated process were compared to those of the routine method by assessing productivity, space, equipment and staffing requirements. The data obtained were evaluated in order to estimate the impact of implementing the Atreus 3C system in the routine setting of the blood centre. Yield and in vitro quality of the final blood components processed with the two systems were evaluated and compared. RESULTS: The Atreus 3C system enabled higher throughput while requiring less space and employee time by decreasing the amount of equipment and processing time per unit of whole blood processed. Whole blood units processed on the Atreus 3C system gave a higher platelet yield, a similar amount of red blood cells and a smaller volume of plasma. DISCUSSION: These results support the conclusion that the Atreus 3C system produces blood components meeting quality requirements while providing a high operational efficiency. Implementation of the Atreus 3C system could result in a large organisational improvement. PMID- 22044960 TI - Hypercoagulability in congenital haemolytic anaemias. PMID- 22044959 TI - Autologous blood in obstetrics: where are we going now? PMID- 22044961 TI - Oxidative injury as contributory factor for red cells storage lesion during twenty eight days of storage. AB - BACKGROUND: Storage of red blood cells at 4 degrees C is associated with deleterious metabolic and biochemical changes, collectively referred to as "storage lesions". Lipid peroxidation of the red cell membrane leading to lysis contributes to these storage lesions. The aim of the present study was to investigate oxidative injury to red cells during storage for 28 days and its correlation with markers of red cell membrane damage. MATERIALS AND METHODS: Samples from 30 units of red blood cells stored at 4 degrees C for 28 days were withdrawn aseptically on day 0, day 14 and day 28 of storage. Markers of membrane damage including plasma haemoglobin, plasma potassium and lactate dehydrogenase (LDH) concentrations and markers of oxidative injury such as malondialdehyde (MDA) levels, haemoglobin oxidation and osmotic fragility were studied in all samples. RESULTS: Statistically significant (p<0.001) increases in the mean values of plasma haemoglobin, plasma potassium, LDH and markers of oxidative injury such as MDA and haemoglobin oxidation were observed over the storage period of 28 days. Direct correlations of MDA and haemoglobin oxidation with membrane damage, as reflected by plasma haemoglobin concentration, were observed. CONCLUSION: Oxidative injury to red blood cells during storage leads to membrane damage and lysis. The role of antioxidants in the prevention of this deleterious effect of storage warrants investigation. PMID- 22044962 TI - Risk of intimate partner violence among young adult males with childhood ADHD. AB - OBJECTIVE: Research has clearly documented the social dysfunction of youth with ADHD. However, little is known about the interpersonal relationships of adults diagnosed with ADHD in childhood, including rates of intimate partner violence (IPV). METHOD: Using data from the Pittsburgh ADHD Longitudinal Study, analyses compared the level of IPV (verbal aggression, violence) reported by young adult (18- to 25-year-old) males with childhood ADHD (n = 125) with reports by demographically similar males without ADHD histories (n = 88). RESULTS: Males with childhood ADHD, especially those with conduct problems persisting from childhood, were more likely to be verbally aggressive and violent with romantic partners than males without histories of ADHD or conduct problems. CONCLUSIONS: Research is needed to replicate these findings, to explore potential mechanisms, and to develop effective interventions for romantic relationship discord among young adults with ADHD histories, especially those with persistent conduct problems. PMID- 22044963 TI - Expression of a bacterial chitosanase in rice plants improves disease resistance to the rice blast fungus Magnaporthe oryzae. AB - Plant fungal pathogens change their cell wall components during the infection process to avoid degradation by host lytic enzymes, and conversion of the cell wall chitin to chitosan is likely to be one infection strategy of pathogens. Thus, introduction of chitosan-degradation activity into plants is expected to improve fungal disease resistance. Chitosanase has been found in bacteria and fungi, but not in higher plants. Here, we demonstrate that chitosanase, Cho1, from Bacillus circulans MH-K1 has antifungal activity against the rice blast fungus Magnaporthe oryzae. Introduction of the cho1 gene conferred chitosanase activity to rice cells. Transgenic rice plants expressing Cho1 designed to be localized in the apoplast showed increased resistance to M. oryzae accompanied by increased generation of hydrogen peroxide in the infected epidermal cells. These results strongly suggest that chitosan exists in the enzyme-accessible surface of M. oryzae during the infection process and that the enhancement of disease resistance is attributable to the antifungal activity of the secreted Cho1 and to increased elicitation of the host defense response. PMID- 22044964 TI - Beyond gibberellins and abscisic acid: how ethylene and jasmonates control seed germination. AB - Appropriate responses of seeds and fruits to environmental factors are key traits that control the establishment of a species in a particular ecosystem. Adaptation of germination to abiotic stresses and changing environmental conditions is decisive for fitness and survival of a species. Two opposing forces provide the basic physiological mechanism for the control of seed germination: the increasing growth potential of the embryo and the restraint weakening of the various covering layers (seed envelopes), including the endosperm which is present to a various extent in the mature seeds of most angiosperms. Gibberellins (GA), abscisic acid (ABA) and ethylene signaling and metabolism mediate environmental cues and in turn influence developmental processes like seed germination. Cross species work has demonstrated that GA, ABA and ethylene interact during the regulation of endosperm weakening, which is at least partly based on evolutionarily conserved mechanisms. We summarize the recent progress made in unraveling how ethylene promotes germination and acts as an antagonist of ABA. Far less is known about jasmonates in seeds for which we summarize the current knowledge about their role in seeds. While it seems very clear that jasmonates inhibit germination, the results obtained so far are partly contradictory and depend on future research to reach final conclusions on the mode of jasmonate action during seed germination. Understanding the mechanisms underlying the control of seed germination and its hormonal regulation is not only of academic interest, but is also the ultimate basis for further improving crop establishment and yield, and is therefore of common importance. PMID- 22044965 TI - Arabidopsis ACA7, encoding a putative auto-regulated Ca(2+)-ATPase, is required for normal pollen development. AB - Microgametogenesis is a complex process that involves numerous well-coordinated cell activities, ending with the production of pollen grains. Pollen development has been studied at the cytological level in Arabidopsis and other plant species, where its temporal time course has been defined. However, the molecular mechanism underlying this process is still unclear, since a relative small number of genes and/or processes have been identified as essential for pollen development. We have designed a methodology to select candidate genes for functional analysis, based on transcriptomic data obtained from different stages of pollen development. From our analyses, we selected At2g22950 as a candidate gene; this gene encodes a protein belonging to the auto-regulated Ca(2+)-ATPase family, ACA7. Microarray data indicate that ACA7 is expressed exclusively in developing pollen grains, with the highest level of mRNA at the time of the second pollen mitosis. Our RT-PCR experiments showed that ACA7 mRNA is detected exclusively in developing flowers. Confocal microscopy experiments showed a plasma membrane localization for the recombinant GFP:ACA7 protein. We identified two different insertional mutant lines, aca7-1 and aca7-2; plants from both mutant lines displayed a normal vegetative development but showed large amounts of dead pollen grains in mature flowers assayed by Alexander's staining. Histological analysis indicated that abnormalities are detected after the first pollen mitosis and we found a strong correlation between ACA7 mRNA accumulation and the severity of the phenotype. Our results indicate that ACA7 is a plasma membrane protein that has an important role during pollen development, possibly through regulation of Ca(2+) homeostasis. PMID- 22044967 TI - Management options for symptomatic stenosis after laparoscopic vertical sleeve gastrectomy in the morbidly obese. AB - BACKGROUND: This study aimed to determine the incidence, etiology, and management options for symptomatic stenosis (SS) after laparoscopic sleeve gastrectomy (LSG). METHODS: A retrospective study reviewed morbidly obese patients who underwent LSG between October 2008 and December 2010 to identify patients treated for SS. RESULTS: In this study, 230 patients (83% female) with a mean age of 49.5 years and a mean body mass index (BMI) of 43 kg/m(2) underwent LSG. In 3.5% of these patients (100% female; mean age, 42 years; mean BMI, 42.6 kg/m(2)), SS developed. The LSG procedure was performed using a 36-Fr. bougie and tissue reinforced staplers. Four patients had segmental staple-line imbrication, and seven patients underwent contrast study, with 71.4% demonstrating a fixed narrowing. Endoscopy confirmed short-segment stenoses: seven located at mid-body and one located near the gastroesophageal junction. Endoscopic management was 100% successful. The mean number of dilations was 1.6, and the median balloon size was 15 mm. The mean time from surgery to initial endoscopic intervention was 48.8 days, and the mean time from the first dilation to toleration of a solid diet was 49.6 days. Two patients were referred to our institution after undergoing LSG at another facility. The mean time to the transfer was 28.5 days. The two patients had a mean age of 35 years and a mean BMI of 42.3 kg/m(2). Both patients experienced immediate SS after perioperative complications comprising one staple-line hematoma and one leak. Contrast studies demonstrated minimal passage of contrast through a long-segment stenosis. Both patients underwent multiple endoscopic dilation procedures and endoluminal stenting, ultimately requiring laparoscopic conversion to Roux-en-Y gastric bypass. The mean time from the initial surgery to the surgical revision was 77 days, and the mean time after the first intervention to tolerance of a solid diet was 82 days. CONCLUSION: Symptomatic short-segment stenoses after LSG may be treated successfully with endoscopic balloon dilation. Long-segment stenoses that do not respond to endoscopic techniques may ultimately require conversion to Roux-en-Y gastric bypass. PMID- 22044968 TI - Robotic vs. laparoscopic colorectal surgery: an institutional experience. AB - BACKGROUND: Robotic colorectal surgery is gaining interest in general and colorectal surgery. The use of the da Vinci((r)) Robotic system has been postulated to improve outcomes, primarily by increasing the dexterity and facility with which complex dissections can be performed. We report a large, single institution, comparative study of laparoscopic and robotic colectomies, attempting to better elucidate the benefits of robotic surgery in patients with colorectal disease. METHODS: We conducted a retrospective review of 171 patients who underwent robotic and laparoscopic colectomies (79 and 92, respectively) at our institution between November 2004 and November 2009. Patients in both groups had well-matched preoperative parameters. All cases were further subdivided by their anatomical location into right-sided and left-sided colectomy, and analysis was performed within these two subgroups. Perioperative outcomes reported include operative time, operative blood loss, time to return of bowel function, time to discontinuation of patient controlled analgesia, length of stay, and intraoperative or postoperative complications. RESULTS: Our results indicate that there is no statistical difference in length of stay, time to return of bowel function, and time to discontinuation of patient-controlled analgesia between robotic and laparoscopic left and right colectomies. Interestingly, the total procedure time difference between the laparoscopic and robotic colectomies was much smaller than previously published accounts (mean 140 min vs. 135 min for right colectomy; mean 168 min vs. 203 min for left colectomy). CONCLUSIONS: Our study is one of the largest reviews of robotic colorectal surgery to date. We believe that our results further demonstrate the equivalence of robotic surgery to laparoscopic surgery in colorectal procedures. Future research should focus on surgeon-specific variables, such as comfort, ergonomics, distractibility, and ease of use, as other ways to potentially distinguish robotic from laparoscopic colorectal surgery. PMID- 22044969 TI - Qualitative and quantitative analysis of women's perceptions of transvaginal surgery. AB - BACKGROUND: Prior surveys evaluating women's perceptions of transvaginal surgery both support and refute the acceptability of transvaginal access. Most surveys employed mainly quantitative analysis, limiting the insight into the women's perspective. In this mixed-methods study, we include qualitative and quantitative methodology to assess women's perceptions of transvaginal procedures. METHODS: Women seen at the outpatient clinics of a tertiary-care center were asked to complete a survey. Demographics and preferences for appendectomy, cholecystectomy, and tubal ligation were elicited, along with open-ended questions about concerns or benefits of transvaginal access. Multivariate logistic regression models were constructed to examine the impact of age, education, parity, and prior transvaginal procedures on preferences. For the qualitative evaluation, content analysis by independent investigators identified themes, issues, and concerns raised in the comments. RESULTS: The completed survey tool was returned by 409 women (grouped mean age 53 years, mean number of 2 children, 82% >= some college education, and 56% with previous transvaginal procedure). The transvaginal approach was acceptable for tubal ligation to 59%, for appendectomy to 43%, and for cholecystectomy to 41% of the women. The most frequently mentioned factors that would make women prefer a vaginal approach were decreased invasiveness (14.4%), recovery time (13.9%), scarring (13.7%), pain (6%), and surgical entry location relative to organ removed (4.4%). The most frequently mentioned concerns about the vaginal approach were the possibility of complications/safety (14.7%), pain (9%), infection (5.6%), and recovery time (4.9%). A number of women voiced technical concerns about the vaginal approach. CONCLUSIONS: As in prior studies, scarring and pain were important issues to be considered, but recovery time and increased invasiveness were also in the "top five" list. The surveyed women appeared to actively participate in evaluating the technical components of the procedures. PMID- 22044970 TI - Objective hypoesthesia and pain after transabdominal preperitoneal hernioplasty: a prospective, randomized study comparing tissue adhesive versus spiral tacks. AB - BACKGROUND: Irritation of inguinal nerves with laparoscopic hernia repair may cause chronic neuralgia and hypoesthesia. Hypoesthesia in particular is generally not assessed objectively. We objectively investigated hypoesthesia and chronic pain after transabdominal preperitoneal inguinal hernia repair (TAPP) with titanium spiral tacks (STs) compared with tissue adhesive (TA) for mesh fixation. METHODS: Mesh fixation in 80 TAPP procedures was randomized to fixation with ST (n = 40) or TA (n = 40). The outcome parameters included hypoesthesia assessed with von Frey monofilaments, early postoperative and chronic pain with the visual analog scale (VAS), morbidity (surgical-site infection, hematoma/seroma, relapse of hernia, trocar hernia), and recovery time to normal activity. RESULTS: Median (range) follow-up was 38 (13-56) months. Demographic and baseline parameters were similar in the two groups. Prevalence of hypoesthesia was significantly higher at all postoperative times in the ST group (6 weeks: 32 vs. 6%; 6 months: 38 vs. 14%; 12 months: 34 vs. 13%; 13-56 months: 32 vs. 4%). Mean hypoesthesia scores over all time points were significantly higher in the ST group. The percentages of regions with hypoesthesia (abdominal, inguinal, or genitofemoral) following all procedures were higher in the ST group after 6 weeks (14 vs. 2%), 6 months (15 vs. 5%), and 13-56 months (22 vs. 4%). The intensity of pain decreased significantly in both groups over time. CONCLUSIONS: Postoperative hypoesthesia depends on the method of mesh fixation during TAPP and is significantly reduced with TA compared with stapling. PMID- 22044971 TI - Gastric bypass surgery restores meal stimulation of the anorexigenic gut hormones glucagon-like peptide-1 and peptide YY independently of caloric restriction. AB - BACKGROUND: The effects of gastric bypass surgery on the secretion of the anorexigenic gut-derived hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), independent of caloric restriction and due to different dietary macronutrients, is not well characterized. This study examines the effects of a mixed-nutrient or high-fat liquid meal on the postprandial stimulation of GLP-1 and PYY following gastric bypass or equivalent hypocaloric diet. METHODS: Total PYY and active GLP-1 were measured fasting and at multiple points after standardized mixed-nutrient and high-fat liquid meals in two matched groups of obese subjects. The meal stimulation tests were performed before and 14.6 +/- 3.3 days after gastric bypass (GBP, n = 10) and before and after a 7-day hypocaloric liquid diet matching the post-GBP diet (control, n = 10). RESULTS: Mixed-nutrient and high-fat postprandial GLP-1 levels increased following GBP (mixed-nutrient peak: 85.0 +/- 28.6-323 +/- 51 pg/ml, P < 0.01; high-fat peak: 81.8 +/- 9.6-278 +/- 49 pg/ml, P < 0.01), but not after diet (mixed-nutrient peak: 104.4 +/- 9.4 114.9 +/- 15.8 pg/ml, P = NS; high-fat peak: 118.1 +/- 16.4-104.4 +/- 10.8 pg/ml, P = NS). The postprandial PYY response also increased after GBP but not diet, though the increase in peak PYY did not reach statistical significance (GBP mixed nutrient peak: 134.8 +/- 26.0-220.7 +/- 52.9 pg/ml, P = 0.09; GBP high-fat peak: 142.1 +/- 34.6-197.9 +/- 12.7 pg/ml, P = 0.07; diet mixed-nutrient peak: 99.8 +/- 8.0-101.1 +/- 13.3 pg/ml, P = NS; diet high-fat peak: 105.0 +/- 8.8-103.1 +/- 11.8 pg/ml, P = NS). The postprandial GLP-1 response was not affected by the macronutrient content of the meal. However, following GBP the mixed-nutrient PYY total area under the curve (AUC(0-120)) was significantly greater than the high fat PYY AUC(0-120) (22,081 +/- 5,662 pg/ml min vs. 18,711 +/- 1,811 pg/ml min, P = 0.04). CONCLUSIONS: Following GBP there is an increase in the postprandial stimulation of PYY and GLP-1 that is independent of caloric restriction. The phenomenon of "bariatric surgery-induced anorexia" may be linked to the increased levels after GBP. PMID- 22044972 TI - Recurrent hepatocellular carcinoma successfully treated with laparoscopic thermal ablation. AB - BACKGROUND: Aggressive treatment of intrahepatic recurrence of hepatocellular carcinoma (HCC) increases patients' survival. This study aimed to evaluate laparoscopic thermal ablation (TA) in the treatment of intrahepatic HCC recurrences. METHODS: A retrospective analysis was performed on 88 patients (REC group) who underwent laparoscopic TA after prior TA (66 patients.) or partial hepatic resection (HR) (22 patients) as initial local treatment. Another 170 patients with primary HCC tumors (PRIM group) were regarded as the control group. RESULTS: The postoperative morbidity rates were similar for the patients with prior TA (18%) and those with prior HR (21%) (nonsignificant difference [NS]). The overall survival rates were not significantly different between the two groups (3-year survival rates of 59 and 78%, respectively; P = 0.1662). Moreover, the disease-free survival (DFS) rates did not differ significantly between the patients with prior TA and those with prior HR (3-year DFS of 21 and 8%, respectively; P = 0.1911). The incidences of morbidity in the whole REC (21%) and PRIM (20%) groups were similar (P = NS), and no mortality occurred in either group (0%). The cumulative 3-year survival rate was 63% in the REC group and 59% in the PRIM group (P = 0.5739), whereas the 3-year DFS rate was 17% in the REC group and 22% in the PRIM group (P = 0.5266). CONCLUSION: Laparoscopic TA can be performed safely and may be effective for intrahepatic HCC recurrence after prior TA or HR. It leads to survival and DFS rates similar to those obtained using laparoscopic TA for primary HCC without increasing morbidity. Laparoscopic TA could be proposed as first-line treatment of intrahepatic HCC recurrence for selected patients. PMID- 22044973 TI - Learning curve for robot-assisted Roux-en-Y gastric bypass. AB - BACKGROUND: Robot-assisted Roux-en-Y gastric bypass (RYGBP) is rapidly evolving as an important surgical approach in the bariatric field. However, the specific learning curve associated with this new approach remains poorly investigated. This study aimed to evaluate the learning curve for robot-assisted RYGBP. METHODS: A series of 64 consecutive robot-assisted RYGBP procedures were performed between December 2008 and December 2010 by a single surgeon already experienced in advanced laparoscopic procedures but not in bariatric surgery. All data were collected prospectively in a database and reviewed retrospectively. The learning curve was evaluated using the cumulative sum (CUSUM) method. RESULTS: Women comprised 76.6% and men 23.4% of this series. These patients had a mean age of 43 years and a mean body mass index (BMI) of 44.5 kg/m(2). The mean operative time (OT) was 238.1 min (range, 150-400 min). A total of six complications occurred (9.4%). The CUSUM learning curve consisted of two distinct phases: phase 1 (the initial 14 cases; mean OT, 288.9 min) and phase 2 (the subsequent cases; mean OT, 223.6 min), which represented the mastery phase, with a decrease in OT (P = 0.0001). The two groups were similar in terms of gender, age, and BMI. The two phases did not differ in terms of complications or hospital stay. CONCLUSIONS: This series confirms previous study findings concerning the feasibility and the safety of robotic RYGBP even after a limited experience with laparoscopic RYGBP. The data reported in this article suggest that the learning phase for robot-assisted RYGBP can be achieved with 14 cases. PMID- 22044974 TI - Video. Radiofrequency fulguration of the spleen under laparoscopy to stop iatrogenic hemorrhage. AB - BACKGROUND: Iatrogenic splenic injury is a potentially serious complication of laparoscopic surgery associated with significant morbidity and mortality. It also has an impact on the prognosis of patients who undergo surgery for digestive cancer. For iatrogenic splenic injury, splenic salvage is the ultimate goal. Various surgical techniques have been developed to achieve hemostasis of the spleen. Radiofrequency fulguration (RF) is reported to be a safe method in an animal trauma model. However, only three articles report RF for the control of splenic hemorrhage in human patients. METHODS: A bicentric, retrospective study was performed. From January 2009 to September 2010, all iatrogenic splenic hemorrhages uncontrolled by conventional hemostasis techniques were treated using RF. The splenic injuries were classified according to the Moore classification and a postoperative, abdominal computed tomography scan was performed for each patient. RF was performed with a straight electrode needle (Integra, Tuttlingen, Germany) introduced percutaneously into the spleen. The electrode was infused with isotonic saline and connected to a 500-kHz generator (Elektrotom 106 HFTT; Berchtold, Tuttlingen, Germany). During the high-frequency coagulation (375 kHz), electrode saline perfusion was automatically regulated from 30 to 110 ml/h according to the variation in tissue impedance, and the power of the generator was kept at 50 W. RESULTS: Three patients (2 men and 1 woman) with a median age of 58 years underwent splenic RF. The splenic injuries (grade 3, Moore classification) occurred during laparoscopic proctectomy in two cases and during laparoscopic gastrectomy in one case. It was possible to achieve complete hemostasis in all the patients during a median time of 10 min. The median blood loss was 100 ml, with no blood transfusion. No splenectomy was necessary, and no postoperative splenic infarction was diagnosed. No conversion was performed. There was no postoperative morbidity or mortality. No recurrent splenic hemorrhage occurred during the follow-up period. The financial cost was 350 per RF. CONCLUSION: Although RF could potentially induce splenic infarction in the event of a large-scale fulguration, it is a safe, quick, and effective spleen preserving technique for stopping an iatrogenic splenic hemorrhage when conventional hemostasis techniques fail. Furthermore, it is readily available and easy to set up in an emergency situation and can be performed easily by laparoscopy without an additional port. PMID- 22044975 TI - Effect of haptic feedback in laparoscopic surgery skill acquisition. AB - BACKGROUND: The benefits of haptic feedback in laparoscopic surgery training simulators is a topic of debate in the literature. It is hypothesized that novice surgeons may not benefit from the haptic information, especially during the initial phase of learning a new task. Therefore, provision of haptic feedback to novice trainees in the early stage of training may be distracting and detrimental to learning. A controlled experiment was conducted to examine the effect of haptic feedback on the learning curve of a complex laparoscopic suturing and knot tying task. METHODS: The ProMIS and the MIST-VR surgical simulators were used to represent conditions with and without haptic feedback, respectively. A total of 20 novice subjects (10 per simulator) were trained to perform suturing and knot tying and practiced the tasks in 18 sessions of 1 h each. RESULTS: At the end of the 3-week training period, the subjects performed equally fast but more consistently with haptics (ProMIS) than without haptics (MIST-VR). The subjects showed a slightly higher learning rate and reached the first plateau of the learning curve earlier with haptic feedback. CONCLUSION: In general, learning with haptic feedback was significantly better than learning without it for a laparoscopic suturing and knot-tying task, but only during the first 5 h of training. Haptic feedback may not be warranted in laparoscopic surgical trainers. The benefits of a shorter time to the first performance plateau and more consistent initial performance should be balanced with the cost of implementing haptic feedback in surgical simulators. PMID- 22044976 TI - A randomized comparison of laparoscopic, magnetically anchored, and flexible endoscopic cameras in performance and workload between laparoscopic and single incision surgery. AB - BACKGROUND: This study aimed to evaluate the surgeon performance and workload of a next-generation magnetically anchored camera compared with laparoscopic and flexible endoscopic imaging systems for laparoscopic and single-site laparoscopy (SSL) settings. METHODS: The cameras included a 5-mm 30 degrees laparoscope (LAP), a magnetically anchored (MAGS) camera, and a flexible endoscope (ENDO). The three camera systems were evaluated using standardized optical characteristic tests. Each system was used in random order for visualization during performance of a standardized suturing task by four surgeons. Each participant performed three to five consecutive repetitions as a surgeon and also served as a camera driver for other surgeons. Ex vivo testing was conducted in a laparoscopic multiport and SSL layout using a box trainer. In vivo testing was performed only in the multiport configuration and used a previously validated live porcine Nissen model. RESULTS: Optical testing showed superior resolution for MAGS at 5 and 10 cm compared with LAP or ENDO. The field of view ranged from 39 to 99 degrees . The depth of focus was almost three times greater for MAGS (6-270 mm) than for LAP (2-88 mm) or ENDO (1-93 mm). Both ex vivo and in vivo multiport combined surgeon performance was significantly better for LAP than for ENDO, but no significant differences were detected for MAGS. For multiport testing, workload ratings were significantly less ex vivo for LAP and MAGS than for ENDO and less in vivo for LAP than for MAGS or ENDO. For ex vivo SSL, no significant performance differences were detected, but camera drivers rated the workload significantly less for MAGS than for LAP or ENDO. CONCLUSION: The data suggest that the improved imaging element of the next-generation MAGS camera has optical and performance characteristics that meet or exceed those of the LAP or ENDO systems and that the MAGS camera may be especially useful for SSL. Further refinements of the MAGS camera are encouraged. PMID- 22044978 TI - Endoscopic bilateral adrenalectomy in patients with ectopic Cushing's syndrome. AB - BACKGROUND: Bilateral adrenalectomy (BLA) is a treatment option to alleviate symptoms in patients with ectopic Cushing's syndrome (ECS) for whom surgical treatment of the responsible nonpituitary tumor is not possible. ECS patients have an increased risk for complications, because of high cortisol levels, poor clinical condition, and metabolic disturbances. This study aims to evaluate the safety and long-term efficacy of endoscopic BLA for ECS. METHODS: From 1990 to present, 38 patients were diagnosed and treated for ECS in the Erasmus University Medical Center, a tertiary referral center. Twenty-four patients were treated with BLA (21 endoscopic, 3 open), 9 patients were treated medically, and 5 patients could be cured by complete resection of the adrenocorticotropic hormone (ACTH)-producing tumor. The medical records were retrospectively reviewed and entered into a database. For evaluation of the efficacy of BLA, preoperative biochemical and physical symptoms were assessed and compared with postoperative data. RESULTS: Endoscopic BLA was successfully completed in 20 of the 21 patients; one required conversion to open BLA. Intraoperative complications occurred in two (10%) patients, and postoperative complications occurred in three (14%) patients. Median hospitalization was 9 (2-95) days, and median operating time was 246 (205-347) min. Hypercortisolism was resolved in all patients. Improvements of hypertension, body weight, Cushingoid appearance, impaired muscle strength, and ankle edema were achieved in 87, 90, 65, 61, and 78% of the patients, respectively. Resolution of diabetes, hypokalemia, and metabolic alkalosis was achieved in 33, 89, and 80%, respectively. CONCLUSION: Endoscopic BLA is a safe and effective treatment for patients with ectopic Cushing's syndrome. PMID- 22044977 TI - SAGES guidelines for the surgical treatment of esophageal achalasia. PMID- 22044979 TI - Impact of T3 thoracoscopic sympathectomy on pupillary function: a cause of partial Horner's syndrome? AB - BACKGROUND: Thoracoscopic bilateral sympathicolysis of the T3 sympathetic ganglia is an effective treatment for palmar hyperhidrosis, though not without potential complications and consequences such as Horner's syndrome. The objective of our study is to evaluate the repercussion of T3 sympathetic denervation on pupillary tone in patients with primary hyperhidrosis. METHODS: A prospective descriptive study of 25 patients (50 pupils) ranging in age from 18 to 40 years with an indication of T3 sympathectomy for palmar hyperhidrosis or palmar-plantar hyperhidrosis from 1 December 2009 to 31 December 2010 was carried out. We excluded all patients with previous eye surgery or other ocular pathologies and those with pathologies that contraindicate denervation surgery and ocular study. All patients were evaluated before surgery and at 24 h and 1 month after sympathetic denervation. Pupil/iris (P/I) ratio was measured before and after instillation of sympathicomimetic eye drops containing 1% apraclonidine. RESULTS: No statistically significant differences were found when we compared the preoperative P/I ratio of the left eyes versus the right eyes (P = 0.917). We found statistically significant differences (P < 0.001) between the preoperative P/I ratio [0.40 mm (standard deviation, SD 0.07 mm)] and the postoperative basal ratio [0.33 (SD 0.05)] at 24 h. The P/I ratio at 24 h increased from 0.33 to 0.36 (SD 0.09), a nonsignificant increase (P = 0.45), after instillation of medicated eye drops. No differences were observed between the preoperative [0.40 (SD 0.07)] and 1-month basal values [0.38 (SD 0.07)], and instillation of apraclonidine no longer induced a hypersensitivity response. CONCLUSIONS: T3 sympathectomy leads to subclinical pupillary dysfunction with a tendency for miosis, even though this impairment is not generally evident on standard physical examination or reported by patients. This subclinical dysfunction may be caused by injury to an undefined group of presympathetic nerve cell axons in caudocranial direction that communicate with the cervical sympathetic ganglia and whose function is mydriatic pupillary innervation. PMID- 22044980 TI - The role of short-limb Roux-en-Y reconstruction for failed antireflux surgery: a single-center 5-year experience. AB - INTRODUCTION: Revisionary fundoplication is the mainstay of treatment for failed previous fundoplication, but is not always feasible. We report our experience with use of short-limb Roux-en-Y (RNY) reconstruction for failed antireflux procedures. METHODS: Prospectively collected data were retrospectively analyzed for morbidity, mortality, pre- and postprocedure symptom scores (scale 0-3), body mass index (BMI), and patient satisfaction (scale 1-10). RESULTS: Seventy-two patients with 1-4 (median 1) previous antireflux procedures underwent RNY reconstruction, either to gastric pouch (n = 64) or to the esophagus (n = 8). There were 37 laparoscopic, 24 open abdominal, and two combined thoracic abdominal procedures. Nine additional patients underwent conversion from laparoscopy to open surgery. Mean follow-up of 20.7 months (+/- 12.9 months) was available in 63 (88%) patients. The overall median scores for heartburn, regurgitation, dysphagia, chest pain, and nausea were 0 or 1. There were 72 major and minor complications noted that affected 33 (46%) patients, with no in hospital or 30-day mortality observed. The most common complications were anastomotic strictures, bowel obstructions, respiratory complications, and dumping. Mean postoperative BMI was 24.6 (+/- 4.4) kg/m(2) compared with preoperative BMI of 31.4 (+/- 6.1) kg/m(2). Mean reported satisfaction score was 8.2 (+/- 2.1), and 89% of the patients would recommend the procedure to a friend. Pre- and postoperative symptoms could be compared in 57 patients, and significant decrease in median symptom scores for heartburn (2-0, P < 0.05), regurgitation (1 0, P < 0.05), and dysphagia (2-0, P < 0.05) was confirmed. There was an increase in reported nausea (0-1, P < 0.05). CONCLUSIONS: Short-limb RNY reconstruction is an effective remedial procedure for a subset of patients with failed antireflux surgery, but morbidity is significant. PMID- 22044981 TI - Comparison of complications after laparoscopy-assisted distal gastrectomy and open distal gastrectomy for gastric cancer using the Clavien-Dindo classification. AB - BACKGROUND: The complication rate after surgery for gastric cancer varies according to the particular definition of morbidity. Complications after gastrectomy should be reported using a standardized method. The present study retrospectively analyzed patient outcomes after open distal gastrectomy (ODG) and laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer using a standardized classification system of the severity of complications (the Clavien Dindo system). METHODS: A total of 1,631 patients who underwent curative ODG or LADG for gastric adenocarcinoma between May 2003 and December 2009 were included in the study and any risk factors related to complications were analyzed. RESULTS: Six hundred twenty-nine patients were treated with ODG and 1,002 with LADG. Postoperative complications were less frequent in the LADG group than in the ODG group (25.3% vs. 40.1%, P < 0.001), and fewer major complications (Clavien-Dindo classification >=IIIa) were observed with LADG than with ODG (2.1% vs. 5.4%, P < 0.001). Multivariate analysis showed that the laparoscopic surgical approach correlated with significantly fewer overall and major complications in patients with stage I disease. CONCLUSION: Using the Clavien-Dindo system, we observed fewer complications with LADG than with ODG. This shows that the laparoscopic approach for treating gastric cancer is less invasive than the open approach in terms of morbidity. Future studies will be needed to confirm this. PMID- 22044982 TI - Single-port laparoscopic surgery is applicable to most gynecologic surgery: a single surgeon's experience. AB - BACKGROUND: The aim of this study was to evaluate the use of single-port laparoscopic surgery in benign gynecologic diseases and to examine its impact on surgical outcomes. METHODS: The medical records of 500 consecutive patients who underwent laparotomy or laparoscopic surgery performed by a single surgeon for benign disease from August 2008 to October 2010 were retrospectively reviewed. RESULTS: The surgeries included hysterectomy (n = 239), adnexectomy (n = 212), and myomectomy (n = 51). The indications for surgery included adnexal lesions (48.1%), uterine fibroids (37.8%), preinvasive cervical disease (7.5%), and endometrial pathology (6.6%). Twenty-nine percent of the first 100 cases were single-port laparoscopic surgeries. The percentages increased in the second (62%), third (72%), fourth (71%), and last (86%) 100 cases. The percentages of laparotomy and multiport laparoscopy were 23% and 48%, respectively, in the first 100 cases; however, in the last 100 cases, the percentages dropped to 4% and 10%, respectively. A significant reduction in estimated blood loss and length of hospital stay was observed for all diseases. No differences were identified in the median operative time or complication rate over the study period. CONCLUSION: Single-port laparoscopic surgery can be applied to most benign gynecologic surgery without detrimental effects on clinical outcomes. PMID- 22044983 TI - Outcome of laparoscopic modified Duhamel procedure with Z-shaped anastomosis for Hirschsprung's disease. AB - BACKGROUND: Several laparoscopic Duhamel-type procedures for Hirschsprung's disease (HD) have been reported, but laparoscopic, Z-shaped, colorectal, side-to side anastomosis has not been described. Z-shaped anastomosis has been used as the treatment of choice for HD at our clinic for a long time. A laparoscopic approach was adopted to perform this Z-shaped anastomosis in 2001. We describe herein our experiences with laparoscopic Z-shaped anastomosis and evaluate the clinical outcomes. METHODS: Between 2001 and 2010, 26 children with rectosigmoid HD underwent a laparoscopic modified Duhamel procedure comprising Z-shaped anastomosis. Mean age at operation was 17.2 months. Mean weight was 8.7 kg. No children had a colostomy. Seven children had trisomy 21 and one had Klinefelter syndrome. Laparoscopic modified Duhamel procedure was performed using three 5-mm trocars. Intra- and postoperative complications and functional outcomes were evaluated. Patients with trisomy 21 were excluded from the functional evaluation. RESULTS: The operation was completed laparoscopically for 25 of the 26 patients, with only one patient requiring conversion to an open procedure because of injury to the ureter. Mean operating time was 296 min. In one case, a minor leak was observed. No infections or related complications were observed. Mean follow-up period was 50.4 months. Sudden death secondary to rotaviral enterocolitis occurred 8 months postoperatively in one case. Twenty-one of the 25 patients (84%) showed episodes of constipation during the early follow-up period, and one child required late myectomy due to sphincter achalasia. As the child grew older, the need for medication was diminished. Of the 14 patients over 4 years old, excluding those patients with trisomy 21, all achieved normal defecation without incontinence. CONCLUSIONS: Our series revealed that all patients over 4 years old who underwent laparoscopic Z-shaped colorectal anastomosis achieved normal defecation without fecal incontinence. Laparoscopic Z-shaped colorectal anastomosis for HD appears feasible and safe to perform with good results. PMID- 22044984 TI - Prevention of postoperative chylothorax with thoracic duct ligation during video assisted thoracoscopic esophagectomy for cancer. AB - BACKGROUND: Minimally invasive esophagectomy (MIE) is a feasible technique that has been shown to be safe for the treatment of esophageal cancer. Chylothorax remains a challenging and potentially life-threatening postoperative complication of MIE. In this retrospective series, we evaluated the results of preventive intraoperative thoracic duct ligation in patients who underwent video-assisted thoracoscopic esophagectomy for cancer. METHODS: From May 2009 to June 2010, 70 video-assisted thoracoscopic esophagectomies for cancer of the esophagus (group A) were performed without prophylactic thoracic duct ligation. Since June 2010, 65 patients (group B) with esophageal cancer underwent video-assisted thoracoscopic esophagectomy with routine ligation of the thoracic duct during the operation. RESULTS: No intraoperative or postoperative complications directly related to thoracic duct ligation were recorded. Postoperative chylothorax occurred in seven patients in group A and in one patient in group B (P = 0.0375). CONCLUSIONS: The results of this study suggest that thoracic duct ligation during video-assisted thoracoscopic esophagectomy for cancer is an effective and safe method for prevention of postoperative chylothorax. PMID- 22044985 TI - Intracorporeal circular-stapled Billroth I anastomosis in single-incision laparoscopic distal gastrectomy. AB - PURPOSE: The intracorporeal anastomotic procedure is one of the most difficult components in single-incision laparoscopic gastrectomy. We describe a simple surgical technique for intracorporeal circular-stapled Billroth I gastroduodenostomy with transumbilical introduction of the instrument. SURGICAL TECHNIQUE: After standard laparoscopic mobilization of the distal stomach using a mini-loop retractor (diameter, 2 mm), a semi-circumference duodenotomy was made just distal to the pyloric ring. The anvil of a circular stapling device, secured with a Prolene suture with a needle, was introduced via the duodenotomy. The suture was advanced anteriorly such that an anvil shaft transfixed the anterior duodenal wall. The duodenum was staple-transected at this point, and the anvil shaft was removed from the duodenum by pulling the thread. The anvil shaft was advanced against the posterior wall of the stomach and tightly grasped by the mini-loop retractor to avoid slippage. After the cartridge-carrying instrument was introduced transumbilically with the pneumoperitoneum maintained using a surgical glove, the anvil shaft was connected with the center rod of the instrument under fine laparoscopic view. The instrument was fired to complete the circular-stapled gastroduodenostomy. RESULTS: We employed this technique in 20 patients. Neither postoperative complications, including anastomotic leakage and stricture, nor postoperative mortality were observed. CONCLUSIONS: Our modified technique for intracorporeal Billroth I reconstruction in single-incision laparoscopic distal gastrectomy is safe and feasible. This technique could be an attractive surgical option for all laparoscopic reconstructive procedures using circular stapling devices. PMID- 22044986 TI - Analysis of parallel and transverse visual cues on the gait of individuals with idiopathic Parkinson's disease. AB - Idiopathic Parkinson's disease (IPD) has been defined as a chronic progressive neurological disorder with characteristics that generate changes in gait pattern. Several studies have reported that appropriate external influences, such as visual or auditory cues may improve the gait pattern of patients with IPD. Therefore, the objective of this study was to use three-dimensional (3D) analysis to evaluate the effects of parallel (PVC) and transverse visual spatial cues (TVCs) on gait variables (spatiotemporal and kinematic) of individuals with IPD. Twelve IPD patients were recruited from the Neurology Clinic, Medical School Hospital, Unicamp. The patients were initially evaluated using a modified Hoehn and Yahr Scale and subsection III of the Unified Parkinson's Disease Rating Scale. A 3D analysis system consisting of six infrared cameras and 18 markers (with a sampling rate of 240 Hz) was used for gait evaluation at the Laboratory for Rehabilitation and Biomechanics of the Locomotor System - Unicamp. Patients were asked to walk down a walkway under the following circumstances: baseline condition (BC, without visual cues), TVCs (20 pieces of white adhesive tape, 5 cm width and 50 cm length, placed 45 cm apart) and PVCs (two adhesive white tapes, 30 cm distance between them, 5 cm width each tape, along the walkway). Compared with the patients without visual cues, gait velocity was higher with the aid of visual cues (PVCs and TVCs, P=0.003), and the percentage of leg stance time was smaller when cues were used (this value was significant for the right leg, P=0.008). In addition, stride length was significantly higher with the use of TVCs (P=0.006) compared with BC and PVCs. Regarding kinematic variables, TVCs resulted in smaller ranges of motion in knee joint flexion at initial contact and higher maximal amplitudes of knee flexion during the oscillatory phase compared with BC and PVCs. In conclusion, The use of TVCs on the gait evaluation results in improved gait variables compared with BC and PVCs. Therefore, the use of TVCs in a rehabilitation plan would be ideal for a physiotherapeutic treatment with emphasis on gait alterations. PMID- 22044987 TI - The responsiveness and correlation between Fugl-Meyer Assessment, Motor Status Scale, and the Action Research Arm Test in chronic stroke with upper-extremity rehabilitation robotic training. AB - Responsiveness of clinical assessments is an important element in the report of clinical effectiveness after rehabilitation. The correlation could reflect the validity of assessments as an indication of clinical performance before and after interventions. This study investigated the correlation and responsiveness of Fugl Meyer Assessment (FMA), Motor Status Scale (MSS), Action Research Arm Test (ARAT) and the Modified Ashworth Scale (MAS), which are used frequently in effectiveness studies of robotic upper-extremity training in stroke rehabilitation. Twenty seven chronic stroke patients were recruited for a 20-session upper-extremity rehabilitation robotic training program. This was a rater-blinded randomized controlled trial. All participants were evaluated with FMA, MSS, ARAT, MAS, and Functional Independent Measure before and after robotic training. Spearman's rank correlation coefficient was applied for the analysis of correlation. The standardized response mean (SRM) and Guyatt's responsiveness index (GRI) were used to analyze responsiveness. Spearman's correlation coefficient showed a significantly high correlation (rho=0.91-0.96) among FMA, MSS, and ARAT and a fair-to-moderate correlation (rho=0.40-0.62) between MAS and the other assessments. FMA, MSS, and MAS on the wrist showed higher responsiveness (SRM=0.85-0.98, GRI=1.59-3.62), whereas ARAT showed relatively less responsiveness (SRM=0.22, GRI=0.81). The results showed that FMA or MSS would be the best choice for evaluating the functional improvement in stroke studies on robotic upper-extremity training with high responsiveness and good correlation with ARAT. MAS could be used separately to evaluate the spasticity changes after intervention in terms of high responsiveness. PMID- 22044988 TI - Impact of nonmotor symptoms on disability in patients with Parkinson's disease. AB - Patients with Parkinson's disease have nonmotor symptoms (NMS) that, although poorly considered, have an impact on their quality of life. In contrast, the effect on disability is not systematically evaluated. Adult patients were consecutively enrolled and administered the Non-Motor Symptoms Questionnaire and the WHO Disability Assessment Schedule. Student's t-test was used to assess the difference in the disability score between patients declaring and not declaring NMS. In total, 86 patients were enrolled and reported a median of nine NMS. Patients reporting symptoms in cognitive, emotional, cardiovascular, and sleep functions, as well as those reporting more than nine symptoms as a whole, also reported higher disability levels. The presence of NMS, including little evaluated areas connected to cardiovascular and sleep functions, negatively impacts disability in patients with Parkinson's disease. PMID- 22044989 TI - Speckled lentiginous nevus: sometimes, but not always, part of a syndrome. PMID- 22044991 TI - Headache in the emergency room: the role of immigrant background on the frequency of serious causes and diagnostic procedures. AB - Headache is the most frequent neurological chief complaint in the emergency room (ER). During diagnostic workup, accurate history taking still is the mainstay for identification of patients with a serious underlying disorder. However, in patients with an immigrant background, language problems and cultural influences on pain perception and pain-associated behavior can pose serious challenges for physicians. Here, we have evaluated the epidemiological characteristics of the chief complaint headache in ER patients with a probable immigrant background. We performed a retrospective study on 4,132 consecutive neurological ER patients. Identification of patients with probable immigrant background was done by a name based algorithm. Epidemiological characteristics of ER headache patients with and without probable immigrant background were evaluated. Patients with a probable immigrant background had a higher frequency of headache as chief complaint compared to age- and sex-matched control patients (32 vs. 21%). In addition, headache patients with a probable immigrant background had a lower frequency of serious causes (5.2 vs. 16%). Approximately eight cranial imaging procedures and three lumbar punctures were performed for one serious diagnosis in patients with a probable immigrant background. In control patients, these ratios were three and one, respectively. Taken together, our data suggest that socio-cultural factors such as migrational status significantly affect pain-associated behavior of headache patients as well as the clinical workup in an ER. Culturally competent care may be optimized by interpreters, standardized headache questionnaires and easy access to cranial imaging when a benign etiology cannot be firmly established. PMID- 22044992 TI - Idiopathic bilateral facial palsy: is a causative role of anti-GM1 ganglioside and herpes simplex type 1 possible? PMID- 22044993 TI - Experimental drying intensifies burning and carbon losses in a northern peatland. AB - For millennia, peatlands have served as an important sink for atmospheric CO(2) and today represent a large soil carbon reservoir. While recent land use and wildfires have reduced carbon sequestration in tropical peatlands, the influence of disturbance on boreal peatlands is uncertain, yet it is important for predicting the fate of northern high-latitude carbon reserves. Here we quantify rates of organic matter storage and combustion losses in a boreal peatland subjected to long-term experimental drainage, a portion of which subsequently burned during a wildfire. We show that drainage doubled rates of organic matter accumulation in the soils of unburned plots. However, drainage also increased carbon losses during wildfire ninefold to 16.8+/-0.2 kg C m(-2), equivalent to a loss of more than 450 years of peat accumulation. Interactions between peatland drainage and fire are likely to cause long-term carbon emissions to far exceed rates of carbon uptake, diminishing the northern peatland carbon sink. PMID- 22044990 TI - The role of glutamate in neuronal ischemic injury: the role of spark in fire. AB - Although being a physiologically important excitatory neurotransmitter, glutamate plays a pivotal role in various neurological disorders including ischemic neurological diseases. Its level is increased during cerebral ischemia with excessive neurological stimulation causing the glutamate-induced neuronal toxicity, excitotoxicity, and this is considered the triggering spark in the ischemic neuronal damage. The glutamatergic stimulation will lead to rise in the intracellular sodium and calcium, and the elevated intracellular calcium will lead to mitochondrial dysfunction, activation of proteases, accumulation of reactive oxygen species and release of nitric oxide. Interruption of the cascades of glutamate-induced cell death during ischemia may provide a way to prevent, or at least reduce, the ischemic damage. Various therapeutic options are suggested interrupting the glutamatergic pathways, e.g., inhibiting the glutamate synthesis or release, increasing its clearance, blocking of its receptors or preventing the rise in intracellular calcium. Development of these strategies may provide future treatment options in the management of ischemic stroke. PMID- 22044994 TI - Super-resolution surface mapping using the trajectories of molecular probes. AB - The surface characterization of 'soft' materials presents a significant scientific challenge, particularly under 'wet' in situ conditions where a wide variety of non-covalent interactions may be relevant. Here we introduce a new chemical imaging method, MAPT (mapping using accumulated probe trajectories) that generates images of surface interactions by distributing different aspects of molecular probe trajectories into distinct locations and then combining many trajectories to generate spatial maps. The maps are super-resolution in nature, because they are accumulated from highly localized single-molecule observations. Unlike other super-resolution techniques, which report only photon or point counts, our analysis generates spatial maps of physical quantities (adsorption rate, desorption probability, local surface diffusion coefficient, surface coverage/occupancy) that are directly associated with the molecular interactions between the probe molecule and the surface. We demonstrate the feasibility of this characterization using a surface patterned with various degrees of hydrophobicity. PMID- 22044995 TI - A high-rate long-life Li4Ti5O12/Li[Ni0.45Co0.1Mn1.45]O4 lithium-ion battery. AB - Lithium batteries are receiving considerable attention as storage devices in the renewable energy and sustainable road transport fields. However, low-cost, long life lithium batteries with higher energy densities are required to facilitate practical application. Here we report a lithium-ion battery that can be cycled at rates as high as 10 C has a life exceeding 500 cycles and an operating temperature range extending from -20 to 55 degrees C. The estimated energy density is 260 W h kg(-1), which is considerably higher than densities delivered by the presently available Li-ion batteries. PMID- 22044996 TI - Broadband polarization-independent resonant light absorption using ultrathin plasmonic super absorbers. AB - Resonant plasmonic and metamaterial structures allow for control of fundamental optical processes such as absorption, emission and refraction at the nanoscale. Considerable recent research has focused on energy absorption processes, and plasmonic nanostructures have been shown to enhance the performance of photovoltaic and thermophotovoltaic cells. Although reducing metallic losses is a widely sought goal in nanophotonics, the design of nanostructured 'black' super absorbers from materials comprising only lossless dielectric materials and highly reflective noble metals represents a new research direction. Here we demonstrate an ultrathin (260 nm) plasmonic super absorber consisting of a metal-insulator metal stack with a nanostructured top silver film composed of crossed trapezoidal arrays. Our super absorber yields broadband and polarization-independent resonant light absorption over the entire visible spectrum (400-700 nm) with an average measured absorption of 0.71 and simulated absorption of 0.85. Proposed nanostructured absorbers open a path to realize ultrathin black metamaterials based on resonant absorption. PMID- 22044997 TI - Giant magnetostriction in annealed Co(1-x)Fe(x) thin-films. AB - Chemical and structural heterogeneity and the resulting interaction of coexisting phases can lead to extraordinary behaviours in oxides, as observed in piezoelectric materials at morphotropic phase boundaries and relaxor ferroelectrics. However, such phenomena are rare in metallic alloys. Here we show that, by tuning the presence of structural heterogeneity in textured Co(1-x)Fe(x) thin films, effective magnetostriction lambda(eff) as large as 260 p.p.m. can be achieved at low-saturation field of ~10 mT. Assuming lambda(100) is the dominant component, this number translates to an upper limit of magnetostriction of lambda(100)~5lambda(eff) >1,000 p.p.m. Microstructural analyses of Co(1-x)Fe(x) films indicate that maximal magnetostriction occurs at compositions near the (fcc+bcc)/bcc phase boundary and originates from precipitation of an equilibrium Co-rich fcc phase embedded in a Fe-rich bcc matrix. The results indicate that the recently proposed heterogeneous magnetostriction mechanism can be used to guide exploration of compounds with unusual magnetoelastic properties. PMID- 22044998 TI - Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution. AB - Retrotransposons had an important role in genome evolution, including the formation of new genes and promoters and the rewiring of gene networks. However, it is unclear how such a repertoire of functions emerged from a relatively limited number of source sequences. Here we show that DNA editing, an antiviral mechanism, accelerated the evolution of mammalian genomes by large-scale modification of their retrotransposon sequences. We find numerous pairs of retrotransposons containing long clusters of G-to-A mutations that cannot be attributed to random mutagenesis. These clusters, which we find across different mammalian genomes and retrotransposon families, are the hallmark of APOBEC3 activity, a potent antiretroviral protein family with cytidine deamination function. As DNA editing simultaneously generates a large number of mutations, each affected element begins its evolutionary trajectory from a unique starting point, thereby increasing the probability of developing a novel function. Our findings thus suggest a potential mechanism for retrotransposon domestication. PMID- 22044999 TI - Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production. AB - Although erythropoietin (Epo) is the cytokine known to regulate erythropoiesis, erythropoietin receptor (EpoR) expression and associated activity beyond haematopoietic tissue remain uncertain. Here we show that mice with EpoR expression restricted to haematopoietic tissues (Tg) develop obesity and insulin resistance. Tg-mice exhibit a decrease in energy expenditure and an increase in white fat mass and adipocyte number. Conversely, Epo treatment of wild-type (WT) mice increases energy expenditure and reduces food intake and fat mass accumulation but shows no effect in body weight of Tg-mice. EpoR is expressed at a high level in white adipose tissue and in the proopiomelanocortin (POMC) neurons of the hypothalamus. Although Epo treatment in WT-mice induces the expression of the polypeptide hormone precursor, POMC, mice lacking EpoR show reduced levels of POMC in the hypothalamus. This study provides the first evidence that mice lacking EpoR in non-haematopoietic tissue become obese and insulin resistant with loss of Epo regulation of energy homeostasis. PMID- 22045000 TI - CD91-dependent programming of T-helper cell responses following heat shock protein immunization. AB - The immunogenic heat shock proteins (HSPs) gp96, hsp70 and calreticulin (CRT) bind to CD91 on antigen-presenting cells (APCs) for cross-presentation of the HSP chaperoned peptides. This event leads to priming of T-cell responses. Here we show that CD91 serves as a signalling receptor for these HSPs, allowing for the maturation of APCs, secretion of cytokines and priming of T-helper (Th) cells. Specifically, CD91 is phosphorylated in response to HSPs in a unique pattern and phospho-CD91 triggers signalling cascades to activate nuclear factor-kappa B. Each HSP-CD91 interaction on APCs stimulates a unique cytokine profile, which dictates priming of specific Th cell subsets. Thus, in a transforming growth factor-beta tumour microenvironment, immunization with CRT, but not gp96 or hsp70, primes Th17-cell responses in a CD91-dependent manner. These results are important for development of T-cell responses in situ in tumour-bearing hosts and for vaccination against cancer and infectious disease. PMID- 22045001 TI - Rational design of a binary metal alloy for chemical vapour deposition growth of uniform single-layer graphene. AB - Controlled growth of high-quality graphene is still the bottleneck of practical applications. The widely used chemical vapour deposition process generally suffers from an uncontrollable carbon precipitation effect that leads to inhomogeneous growth and strong correlation to the growth conditions. Here we report the rational design of a binary metal alloy that effectively suppresses the carbon precipitation process and activates a self-limited growth mechanism for homogeneous monolayer graphene. As demonstrated by an Ni-Mo alloy, the designed binary alloy contains an active catalyst component for carbon source decomposition and graphene growth and a black hole counterpart for trapping the dissolved carbons and forming stable metal carbides. This type of process engineering has been used to grow strictly single-layer graphene with 100% surface coverage and excellent tolerance to variations in growth conditions. With simplicity, scalability and a very large growth window, the presented approach may facilitate graphene research and industrial applications. PMID- 22045003 TI - Review of cervical spine anomalies in genetic syndromes. AB - STUDY DESIGN: Focused review of the literature. OBJECTIVE: Assist spine specialists in diagnosis and treatment of cervical spine anomalies found in selected genetic syndromes. SUMMARY OF BACKGROUND DATA: Cervical spine instability and/or stenosis are potentially debilitating problems in many genetic syndromes. These problems can be overlooked among the other systemic issues more familiar to clinicians and radiologists evaluating these syndromes. It is imperative that spine specialists understand the relevant issues associated with these particular syndromes. METHODS: The literature was reviewed for cervical spine issues in 10 specific syndromes. The information is presented in the following order: First, the identification and treatment of midcervical kyphosis in Larsen syndrome and diastrophic dysplasia (DD). Next, the upper cervical abnormalities seen in Down syndrome, 22q11.2 Deletion syndrome, pseudoachondroplasia, Morquio syndrome, Goldenhar syndrome, spondyloepiphyseal dysplasia congenita, and Kniest dysplasia. Finally, the chin-on-chest deformity of fibrodysplasia ossificans progressiva. RESULTS: Midcervical kyphosis in patients with Larsen syndrome and DD needs to be evaluated and imaged often to track deformity progression. Upper cervical spine instability in Down syndrome is most commonly caused by ligamentous laxity at C1 to C2 and occiput-C1 levels. Nearly 100% of patients with 22q11.2 deletion syndrome have cervical spine abnormalities, but few are symptomatic. Patients with pseudoachondroplasia and Morquio syndrome have C1 to C2 instability related to odontoid dysplasia (hypoplasia and os odontoideum). Morquio patients also have soft tissue glycosaminoglycan deposits, which cause stenosis and lead to myelopathy. Severely affected patients with spondyloepiphyseal dysplasia congenita are at high risk of myelopathy because of atlantoaxial instability in addition to underlying stenosis. Kniest syndrome is associated with atlantoaxial instability. Cervical spine anomalies in Goldenhar syndrome are varied and can be severe. Fibrodysplasia ossificans progressiva features severe, deforming heterotopic ossification that can become life-threatening. CONCLUSION: It is important to be vigilant in the diagnosis and treatment of cervical spine anomalies in patients with genetic syndromes. PMID- 22045002 TI - Integrating the biophysical and molecular mechanisms of auditory hair cell mechanotransduction. AB - Mechanosensation is a primitive and somewhat ubiquitous sense. At the inner ear, sensory hair cells are refined to enhance sensitivity, dynamic range and frequency selectivity. Thirty years ago, mechanisms of mechanotransduction and adaptation were well accounted for by simple mechanical models that incorporated physiological and morphological properties of hair cells. Molecular and genetic tools, coupled with new optical techniques, are now identifying and localizing specific components of the mechanotransduction machinery. These new findings challenge long-standing theories, and require modification of old and development of new models. Future advances require the integration of molecular and physiological data to causally test these new hypotheses. PMID- 22045004 TI - Cross-cultural adaptation and validity of an adapted Brazilian Portuguese version of Scoliosis Research Society-30 questionnaire. AB - STUDY DESIGN: Prospective clinical study developed at a tertiary teaching facility to test an adapted Brazilian Portuguese version of the Scoliosis Research Society-30 (SRS-30) questionnaire. OBJECTIVE: To perform cross-cultural adaptation and evaluate the validity of the adapted Brazilian Portuguese version of SRS-30 questionnaire. SUMMARY OF BACKGROUND DATA: Quality-of-life measurement is a common practice to assess spine diseases. The SRS questionnaires have been proven to be a valid tool in the clinical evaluation of patients diagnosed with idiopathic scoliosis in United States. However, adaptation into languages other than the source language is necessary to allow multinational use respecting cultural and lingual differences. METHODS: A translation/retranslation of the English version of the SRS-30 into Brazilian Portuguese was conducted, and all steps for cross-cultural adaptation process were performed, including a pretest with 20 patients. Sixty-four postoperative patients were submitted to the final version of the Brazilian SRS-30 questionnaire, through oral interviews. The average age of all patients who joined the study was 18.5 years. Internal consistency of the instrument was determined with Cronbach alpha coefficient. RESULTS: The study demonstrated high Cronbach alpha values for 4 of the corresponding domains (pain, 0.68; self-image, 0.75; mental health, 0.78; and function/activity, 0.57). However, the Cronbach alpha value for satisfaction domain (0.28) was considerably lower than the original English questionnaire. The overall Cronbach alpha values achieved 0.85 for all domains. CONCLUSION: The adapted Brazilian version of the SRS-30 questionnaire can be used to assess the outcome of treatment for Brazilian Portuguese-speaking patients with idiopathic scoliosis. PMID- 22045005 TI - Patient comorbidities and complications after spinal surgery: a societal-based cost analysis. AB - STUDY DESIGN: Prospective observational study. OBJECTIVE: To determine how patient comorbidities and perioperative complications after spinal surgery affect the health care costs to society. SUMMARY OF BACKGROUND DATA: Despite efforts to reduce adverse events related to spinal surgery, complications are common and significantly increased by patient comorbidities. METHODS: Patients who underwent spinal surgery at a tertiary academic center during a 6-month period (May 2008 to December 2008) were prospectively followed. All demographic data, comorbidities, procedural information, and complications to 30-day follow-up were recorded. Diagnosis-Related Group codes and Current Procedural Terminology codes were captured for each patient. Direct costs were estimated from a societal perspective, using 2008 Medicare rates of reimbursement. A multivariable analysis was performed to assess the impact of specific patient comorbidities and complications on total health care costs. RESULTS: A total of 226 cases were analyzed. The mean cost of care for cases with complications was greater than that for cases without complications ($13,518.35 [95% confidence interval (CI), $9378.80-$17,657.90]; P < 0.0001). These results were consistent across degenerative, traumatic, and tumor/infection preoperative diagnoses. Cases with major complications were more costly than those with minor complications ($13,714.88 [CI, $6353.02-$21,076.74]; P = 0.0001). Systemic malignancy and preoperative neurological comorbidity were each associated with an increase in the cost of care ($7919 [CI, $2073-$15,225]; P = 0.006] and $5508 [CI, $814 $11,198; P = 0.02]), respectively, when compared with a baseline cost of care derived from all cases in the database. The cost of care was increased by pulmonary complications ($7233 [CI, $3982.53-$11,152.88]; P < 0.0001), instrumentation malposition ($6968 [CI, $1705.90-$14,277.16]; P = 0.0062), new neurological deficit ($4537 [CI, $863.95-$9274.30]; P = 0.013), and by wound infection ($4067 [CI, $1682.79-$6872.39]; P = 0.0004), after adjustment for covariates. CONCLUSION: Both minor and major complications were found to increase the cost of care in a prospective assessment of spine surgery complications. Specific patient comorbidities and perioperative complications are associated with significant increases in the total cost of care to society. PMID- 22045006 TI - Scoliosis Research Society-Schwab adult spinal deformity classification: a validation study. AB - STUDY DESIGN: Inter- and intra-rater variability study. OBJECTIVE: On the basis of a Scoliosis Research Society effort, this study seeks to determine whether the new adult spinal deformity (ASD) classification system is clear and reliable. SUMMARY OF BACKGROUND DATA: A classification of adult ASD can serve several purposes, including consistent characterization of a clinical entity, a basis for comparing different treatments, and recommended treatments. Although pediatric scoliosis classifications are well established, an ASD classification is still being developed. A previous classification developed by Schwab et al has met with clinical relevance but did not include pelvic parameters, which have shown substantial correlation with health-related quality of life measures in recent studies. METHODS: Initiated by the Scoliosis Research Society Adult Deformity Committee, this study revised a previously published classification to include pelvic parameters. Modifier cutoffs were determined using health-related quality of life analysis from a multicenter database of adult deformity patients. Nine readers graded 21 premarked cases twice each, approximately 1 week apart. Inter- and intra-rater variability and agreement were determined for curve type and each modifier separately. Fleiss' kappa was used for reliability measures, with values of 0.00 to 0.20 considered slight, 0.21 to 0.40 fair, 0.41 to 0.60 moderate, 0.61 to 0.80 substantial, and 0.81 to 1.00 almost perfect agreement. RESULTS: Inter rater kappa for curve type was 0.80 and 0.87 for the 2 readings, respectively, with modifier kappas of 0.75 and 0.86, 0.97 and 0.98, and 0.96 and 0.96 for pelvic incidence minus lumbar lordosis (PI-LL), pelvic tilt (PT), and sagittal vertical axis (SVA), respectively. By the second reading, curve type was identified by all readers consistently in 66.7%, PI-LL in 71.4%, PT in 95.2%, and SVA in 90.5% of cases. Intra-rater kappa averaged 0.94 for curve type, 0.88 for PI-LL, 0.97 for PT, and 0.97 for SVA across all readers. CONCLUSION: Data from this study show that there is excellent inter- and intra-rater reliability and inter-rater agreement for curve type and each modifier. The high degree of reliability demonstrates that applying the classification system is easy and consistent. PMID- 22045007 TI - Generation of luminescent noble metal nanodots in cell matrices. AB - Cell matrices were used as rich libraries to screen proteins for the production of luminescent silver and gold nanodots. The study indicates that the proteins for silver and gold nanodot protection are quite different. The identification of such proteins in future may enrich the family of luminescent nanodots. PMID- 22045008 TI - Facile synthesis of monodisperse porous Co3O4 microspheres with superior ethanol sensing properties. AB - A solvothermal method was developed to prepare on a large scale monodisperse porous beta-Co(OH)(2) microspheres consisting of nanoplatelets. Co(3)O(4) microspheres with porous platelets were obtained via subsequent thermal decomposition. These Co(3)O(4) microspheres show much higher ethanol sensitivity and selectivity at a relatively low temperature (135 degrees C) compared with those of commercial Co(3)O(4) nanoparticles. PMID- 22045009 TI - The value of HAZWOPER medical surveillance. AB - Medical surveillance is mandated for workers with potential exposure to hazardous materials. However, little guidance is provided regarding the components of a medical surveillance testing program for these individuals. This article describes the medical surveillance program for a group of 72 employees who respond to hazardous material releases throughout the United States. Conditions related to chemical exposures were not identified in this group. However, several non-occupational health conditions were identified, including a relatively high prevalence of one or more signs of metabolic syndrome. Medical surveillance may provide valuable information regarding an individual's underlying health status and non-occupational health conditions to be addressed at an early stage. PMID- 22045010 TI - The effect of oil spills on workers involved in containment and abatement: the role of the occupational health nurse. AB - The Deepwater Horizon oil spill is the most recent manmade disaster to challenge occupational health nurses caring for a unique worker population. The effects of oil spills on wildlife, marine life, and the ecosystem are well studied and documented, but the effects on workers who contain and abate such disasters are not. These workers can suffer from a multitude of illnesses and injuries, such as ataxia, migraines, and various lung diseases, which can be a challenge for occupational health nurses. PMID- 22045011 TI - An integrated approach to worker self-management and health outcomes: chronic conditions, evidence-based practice, and health coaching. AB - Employee health, prevention, and maintenance programs are growing exponentially each year as costs continue to rise across the health care continuum. Employers and payers alike continue to be challenged by chronic health risks, effective prevention strategies, optimal health and wellness strategies, and programs that are effective for America's work force. In light of these challenges, new and exciting health management approaches are evolving. Changes in occupational health nursing practice can ultimately affect the way occupational health nurses plan, structure, and conduct education sessions. New trends, such as health coaching, embrace the incorporation of health research through evidence-based practice and standards of care to provide the science clinicians need to support interventions. Through knowledge of chronic conditions, evidence-based practice, and health coaching, occupational health nurses possess the skills and strategies that form the foundation necessary to affect and safely guide employee self discovery and self-management and produce optimal health outcomes. PMID- 22045013 TI - Soy isoflavones for the prevention of menopausal symptoms and bone loss--a safe and effective alternative to estrogen? AB - Daily administration of soy isoflavones for 2 years did not prevent bone loss or menopausal symptoms. PMID- 22045014 TI - Recent advances in cooperative ion pairing in asymmetric organocatalysis. AB - Over the last decade, with the surge in the development of organocatalysis, many processes involving chiral ion pairs have emerged as powerful tools in the design of new efficient organocatalysts. This tutorial review focuses on the recent evolutions of these organocatalytic systems in which both anionic and cationic parts are working in a cooperative fashion in order to develop unique catalytic processes which outperform the existing approaches. In this respect, chiral ion pairs opened new avenues in the design of bifunctional organocatalysts by means of combinatorial approaches. PMID- 22045015 TI - Bivalent effects of wheel running on taste conditioning. AB - We replicated the finding of bivalent conditioning of tastes by wheel running by Hughes and Boakes (2008), but without pre-exposure to the wheel. Rats received six days of conditioning with a flavoured solution presented for 10 min before a 40-min placement in a running wheel and another flavoured solution presented for 10 min after. A highly palatable liquid meal replacement was used as a vehicle for the flavours to encourage consumption, allowing us to equate before and after presentation intervals. Relative to a third flavour, we found that the taste preceding wheel running was consumed less, and the taste that followed wheel running was consumed more. Novel wheel running can therefore condition both taste avoidance and taste preference. PMID- 22045016 TI - Statistical analysis of blood pressure measurement errors by oscillometry during surgical operations. AB - OBJECTIVES: Although a validated oscillometry sphygmomanometer satisfies the accuracy criteria of Advancement of Medical Instrumentation (AAMI), its long-term blood pressure (BP) measurement error during operations remains to be determined. We aim to (a) compare the error range throughout surgical operations with the accuracy criteria of AAMI, and (b) investigate the probabilities of occurrence of abnormal, large errors and clinically meaningful errors. METHODS: BP level were measured from 270 participants using oscillometry and arterial cannulation (invasive method) in the same BP monitor throughout surgeries. Mean deviation and SD (oscillometry vs. invasive method) were calculated from 6640 sets of data and presented in the Bland-Altman Plots. Also, the average, the largest, and the smallest measurement errors (errormean, errormax, and errormin) per patient were obtained. The probability distributions of the three types of errors were shown using histograms (percentage vs. SD). In addition, the clinically meaningful large errors (>= 10 mmHg) of the adult patients when their systolic blood pressure (SBP) values were around 90 mmHg were investigated. RESULTS: The mean deviation (1.98 mmHg for SBP and 4.31 mmHg for diastolic blood pressure (DBP) satisfies the AAMI criterion (<= 5 mmHg), but the SD (14.87 mmHg for SBP and 11.21 mmHg for DBP) exceeds the AAMI criterion (<= 8 mmHg). The probability of errormax more than 40 mmHg is 14% for SBP and 6% for DBP. The probability of errormean more than 24 mmHg (4.07% for SBP and 1.48% for DBP), and that of errormin more than 24 mmHg (0.37% for SBP and 0.37% for DBP) are all greater than the criterion of 0.26%. The clinically meaningful errors are found in 28.78% of the adult patients. CONCLUSION: The SD of long-term BP measurement by our oscillometric method during operations exceeds AAMI accuracy criteria. And it is important to be aware of the abnormal large errors and clinically meaningful errors as their probabilities are rather significant. We analyze the possible cause of the major errors and deduce that similar errors may also happen with other oscillometric devices. PMID- 22045017 TI - Relation between carotid intima-media thickness and aortic knob width in patients with essential hypertension. AB - OBJECTIVE: The assessment of subclinical atherosclerosis is important in the evaluation of a hypertensive patient, as it provides information on the severity of the hypertension and the cardiovascular risk. The aim of this study was to determine the usefulness of the aortic knob width measured on chest radiography in the assessment of subclinical atherosclerosis in hypertensive patients. METHOD AND RESULTS: A total of 126 consecutive hypertensive patients were enrolled. In univariate analysis, there was a strong correlation between carotid intima media thickness (CIMT) and aortic knob width (r=0.62, P<0.001). In addition, there were statistically significant correlations between CIMT and age (r=0.42, P<0.001), systolic pressure (r=0.27, P=0.02), diastolic pressure (r=0.28, P<0.03), and pulse pressure (r=0.31, P<0.001). In linear regression analysis, the aortic knob width (beta=0.5, P<0.001), age (beta=0.02, P=0.03), and systolic pressure (beta=0.03, P=0.005) were the only independent predictors of CIMT. CONCLUSION: Observation of aortic knob on chest radiograph in hypertensive patients may provide important predictive information of subclinical atherosclerosis. PMID- 22045018 TI - Agreement comparison between home and clinic blood pressure measurements in 200 Chinese participants. AB - OBJECTIVE: The aim of the present study was to evaluate the agreement, mean difference, prevalence, and control rates of arterial hypertension between clinic (i.e. office) and home blood pressure (BP) measurements in a general population. Variations in home BP between morning and evening measurements and the dynamic changes during 7 days of measurements were also examined. METHODS: A total of 200 participants were selected from three communities in the Beijing area. Patients underwent a clinical interview and measurement of both clinic and home BP. Thresholds for elevated clinic and home BP were defined as at least 140/90 and 135/85 mmHg. RESULTS: Systolic and diastolic BP measured at clinic was higher than at home; the mean difference was 3.1/1.6 mmHg in all participants and 6.2/1.1 mmHg in hypertensive patients. With home BP monitoring, the first day of monitoring showed the highest and most varied (as reflected by standard deviation) BP readings. Home diastolic BP was significantly higher in the morning (76.6 +/- 10.1 mmHg) than in the evening (74.2 +/- 9.8 mmHg, P<0.0001), but home systolic BP was not. The prevalence of hypertension was higher when estimated by clinic versus by home BP (53.0 vs. 39.6%, P=0.025); and the control rate of hypertension tended to be lower when estimated by clinic versus by home BP (56.1 vs. 64.1%, P=0.24). The overall agreement between clinic and home BP in diagnosis of hypertension was 80.3% (kappa coefficient: 0.6). CONCLUSION: The present study in 200 Chinese demonstrates that BP is higher (a) at the clinic setting compared with at home and (b) on the first day of initiating home BP monitoring. There is moderate agreement between clinic and home BP in diagnosing hypertension. As home BP measurements may best represent the 'true' BP level in normotensives and hypertensives, its use in clinical practice should be promoted. PMID- 22045019 TI - Phylogenetic study of the species within the family Streptomycetaceae. AB - Species of the genus Streptomyces, which constitute the vast majority of taxa within the family Streptomycetaceae, are a predominant component of the microbial population in soils throughout the world and have been the subject of extensive isolation and screening efforts over the years because they are a major source of commercially and medically important secondary metabolites. Taxonomic characterization of Streptomyces strains has been a challenge due to the large number of described species, greater than any other microbial genus, resulting from academic and industrial activities. The methods used for characterization have evolved through several phases over the years from those based largely on morphological observations, to subsequent classifications based on numerical taxonomic analyses of standardized sets of phenotypic characters and, most recently, to the use of molecular phylogenetic analyses of gene sequences. The present phylogenetic study examines almost all described species (615 taxa) within the family Streptomycetaceae based on 16S rRNA gene sequences and illustrates the species diversity within this family, which is observed to contain 130 statistically supported clades, as well as many unsupported and single member clusters. Many of the observed clades are consistent with earlier morphological and numerical taxonomic studies, but it is apparent that insufficient variation is present in the 16S rRNA gene sequence within the species of this family to permit bootstrap-supported resolution of relationships between many of the individual clusters. PMID- 22045020 TI - Health-related quality of life among pregnant women with and without depression in Hubei, China. AB - The role of prenatal depression on physical and mental health among women in mainland China has not been previously investigated. The aim of this research was to (a) calculate the prevalence of depression during pregnancy, (b) explore the relationship between depression sample characteristics and quality of life and (c) identify predictors of physical and mental health among pregnant women. This study was designed as a cross-sectional and exploratory survey. A total of 454 pregnant women participated in the study between December 2009 and June 2010 in central China. The data was collected using the Medical Outcomes Study short form 36 v2 and the Edinburgh Postnatal Depression Scale. Participants were recruited at outpatient departments of obstetrics and gynecology. Findings show that almost 40% of pregnant women experience prenatal depression. Depression was significantly associated with physical and mental health-related quality of life (HRQoL). Depression, increased age, higher gestational age, being employed and married were significant predictors of lower physical HRQoL. Depression, lower BMI and having an unintended pregnancy were significant predictors of lower mental HRQoL. Prenatal depression is very common in women from mainland China. Depressed women suffer from impaired physical and mental health; prenatal depression has a negative impact on women's HRQoL. We recommend that antenatal services integrate screening for depression into routine antenatal care. PMID- 22045021 TI - Ego-dystonic pregnancy and prenatal consumption of alcohol among first-time mothers. AB - This study examines predictors of drinking during pregnancy among first-time mothers, in order to distinguish those in need of targeted screening and intervention. Data from the prenatal panel of the Parenting for the First Time study were used in hierarchical linear regressions to determine likelihood of prenatal alcohol consumption among a sample of 645 women. African-American women and those of race/ethnicities other than White were less likely to drink, regardless of age or level of education. Among all women, being in school was associated with abstention (P = 0.05). Among teens, endorsing a perception of feeling "pushed around" was a significant indicator of prenatal alcohol consumption (P = 0.05), as was not having plans for infant feeding shortly before delivery (P = 0.05). Among adults with some level of college education, having a first prenatal visit after the fourth month of pregnancy was a significant predictor of drinking (P = 0.01). This study indicates that women who evidence behaviors or attitudes indicating an ego-dystonic pregnancy (one that is psychologically or emotionally uncomfortable), may be more likely to self medicate and cope via avoidance through drinking. These behaviors and attitudes may be indicators of the need for targeted screening and intervention, as well as indicators of underlying problems to be targeted in treatment. Further, among all women for whom continued education is a possibility, retaining the ability to attend school during the pregnancy can be protective. PMID- 22045022 TI - A conceptual framework for future research on mode of delivery. AB - Our goal was to develop a comprehensive conceptual research framework on mode of delivery and to identify research priorities in this topic area through a Delphi process. We convened a multidisciplinary team of 16 experts (North Carolina Collaborative on Mode of Delivery) representing the fields of obstetrics and gynecology, neonatology, midwifery, epidemiology, psychometrics, decision sciences, bioethics, health care engineering, health economics, health disparities, and women's studies. We finalized the conceptual framework after multiple iterations, including revisions during a one-day in-person conference. The conceptual framework illustrates the causal pathway for mode of delivery and the complex interplay and relationships among patient, fetal, family, provider, cultural, and societal factors as drivers of change from intended to actual mode of delivery. This conceptual framework on mode of delivery will help put specific research ideas into a broader context and identify important knowledge gaps for future investigation. PMID- 22045023 TI - TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis. AB - Kruppel-like factor 5 (KLF5) is a PY motif-containing transcription factor promoting breast cell proliferation. The KLF5 protein is rapidly degraded through the proteasome after ubiquitination by E3 ubiquitin ligases, such as WWP1 and SCF(Fbw7). In this study, we demonstrated that a transcriptional co-activator with the PDZ-binding motif (TAZ) upregulated the KLF5 expression through antagonizing the WWP1-, but not Fbw7-, mediated KLF5 ubiquitination and degradation. TAZ interacted with KLF5 through the WW domain of TAZ and the PY motif of KLF5, which is the binding site for WWP1. TAZ inhibited WWP1-KLF5 protein interaction and WWP1-mediated KLF5 ubiquitination and degradation in a WW domain-dependent manner. Overexpression of TAZ upregulated the protein levels of KLF5 and FGF-BP, which is a well-established KLF5 target gene. In addition, depletion of TAZ in both 184A1 and HCC1937 breast cells downregulated protein levels of KLF5 and FGF-BP and inhibited cell growth. Furthermore, stable depletion of either TAZ or KLF5 significantly suppressed HCC1937 xenograft growth in immunodeficient mice. Knockdown of LATS1, a TAZ upstream inhibitory kinase, up regulated the protein levels of KLF5 and FGF-BP in 184A1 and promoted cell growth through TAZ. Finally, both KLF5 and TAZ were co-expressed in a subset of estrogen receptor alpha-negative breast cell lines. These results, for the first time, suggest that TAZ promotes breast cell growth partially through protecting KLF5 from WWP1-mediated degradation and enhancing KLF5's activities. PMID- 22045024 TI - DHA induces apoptosis and differentiation in human melanoma cells in vitro: involvement of HuR-mediated COX-2 mRNA stabilization and beta-catenin nuclear translocation. AB - The pro-inflammatory phenotype accompanying melanoma progression includes an enhanced expression of cyclooxygenase-2 (COX-2), which plays an important role in the acquisition of apoptosis resistance, and is a suitable target for melanoma prevention and therapy. We observed that the WM266-4 metastatic melanoma cell line showed a constitutive COX-2 expression higher than that of the primary WM115 cells, an increased cytosolic level of the COX-2 messenger RNA (mRNA)-stabilizer human antigen R (HuR) and a lower susceptibility to basal apoptosis. The transfection of HuR siRNA induced apoptosis and reduced COX-2 protein abundance in both the cells. The same effects were observed treating the cells with the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), which reduced the cytoplasmic location and expression of HuR and, correspondently, decreased COX-2 protein expression and induced apoptosis. DHA also decreased the expression and stability of COX-2 mRNA, increased the beta-catenin expression in the nuclei and reduced it in the cytosol, where it forms a complex with HuR and COX-2 mRNA. DHA had also a pro-differentiating effect, which is compatible with the nuclear translocation of beta-catenin. These findings allow us to associate for the first time the constitutive expression of COX-2 in melanoma cells to the HuR-mediated stabilization of its mRNA and suggest that also beta-catenin may play a role in HuR-mediated COX-2 stabilization in these cells. The data demonstrate that the HuR-mediated stabilization of COX-2 may represent a target of DHA action in melanoma cells and suggest the application of DHA in the prevention and therapy of melanoma. PMID- 22045025 TI - Consumption of high omega-3 fatty acid diet suppressed prostate tumorigenesis in C3(1) Tag mice. AB - Prostate cancer incidence and mortality are high in the Western world and high omega-6/omega-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates omega-6 fat content of the Western diet to a high omega-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high omega-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to a high omega-3 diet containing canola oil and fish oil concentrate (FS). High omega-3 diet increased omega-3 and decreased omega-6 fat content of mice tissues. Average weights of prostate and genitourinary bloc were significantly lower in mice consuming high omega-3 diet at adulthood (CO-FS) than mice fed a lifetime high omega-6 diet (CO-CO). There was slower progression of tumorigenesis in dorsalateral prostate of CO-FS than in CO-CO mice. CO-FS mice had slightly lower plasma testosterone level at 24 and 40 weeks, significantly lower estradiol level at 40 weeks and significantly less expressed androgen receptor (AR) in the dorsalateral prostate at 40 weeks than CO CO mice. Consumption of high omega-3 diet lowered the expression of genes expected to increase proliferation and decrease apoptosis in dorsalateral prostate. Our results suggest that consumption of high omega-3 diet slows down prostate tumorigenesis by lowering estradiol, testosterone and AR levels, promoting apoptosis and suppressing cell proliferation in C3(1)Tag mice. PMID- 22045027 TI - Modulation of AKT activity is associated with reversible dormancy in ascites derived epithelial ovarian cancer spheroids. AB - Epithelial ovarian cancer (EOC) metastasis is a direct contributor to high recurrence and low survival for patients with this disease. Metastasis in EOC occurs by cell exfoliation from the primary tumor into the fluid-filled peritoneal cavity, persistence of these cells as non-adherent multicellular aggregates or spheroids and reattachment of spheroids to form secondary lesions. We have recovered native spheroids from ascites fluid and demonstrated that EOC cells within these structures exhibit reduced proliferation, yet regain the capacity to attach and reinitiate cell division. To model this process in vitro for further investigation, primary EOC cells from patient peritoneal fluid were cultured under non-adherent conditions. Here we show that these cells naturally form spheroids resembling those observed in ascites. Spheroids exhibit reduced cell proliferation and a protein expression pattern consistent with cellular quiescence: specifically, decreased phospho-AKT and p45/SKP2 with a concomitant increase in p130/RBL2 and p27(Kip1). However, when spheroids are seeded to an adherent surface, reattachment occurs rapidly and is followed by reinitiation of AKT-dependent cell proliferation. These results were strikingly consistent among numerous clinical specimens and were corroborated in the EOC cell line OVCAR3. Therefore, our data reveal that EOC cells become quiescent when forming spheroids, but reactivate proliferative mechanisms upon attachment to a permissive substratum. Overall, this work utilizes a novel in vitro model of EOC metastasis that employs primary human EOC cells and introduces the important concept of reversible dormancy in EOC pathogenesis. PMID- 22045026 TI - Green tea catechin intervention of reactive oxygen species-mediated ERK pathway activation and chronically induced breast cell carcinogenesis. AB - Long-term exposure to low doses of environmental carcinogens contributes to sporadic human breast cancers. Epidemiologic and experimental studies indicate that green tea catechins (GTCs) may intervene with breast cancer development. We have been developing a chronically induced breast cell carcinogenesis model wherein we repeatedly expose non-cancerous, human breast epithelial MCF10A cells to bioachievable picomolar concentrations of environmental carcinogens, such as 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P), to progressively induce cellular acquisition of cancer-associated properties, as measurable end points. The model is then used as a target to identify non cytotoxic preventive agents effective in suppression of cellular carcinogenesis. Here, we demonstrate, for the first time, a two-step strategy that initially used end points that were transiently induced by short-term exposure to NNK and B[a]P as targets to detect GTCs capable of blocking the acquisition of cancer associated properties and subsequently used end points constantly induced by long term exposure to carcinogens as targets to verify GTCs capable of suppressing carcinogenesis. We detected that short-term exposure to NNK and B[a]P resulted in elevation of reactive oxygen species (ROS), leading to Raf-independent extracellular signal-regulated kinase (ERK) pathway activation and subsequent induction of cell proliferation and DNA damage. These GTCs, at non-cytotoxic levels, were able to suppress chronically induced cellular carcinogenesis by blocking carcinogen-induced ROS elevation, ERK activation, cell proliferation and DNA damage in each exposure cycle. Our model may help accelerate the identification of preventive agents to intervene in carcinogenesis induced by long-term exposure to environmental carcinogens, thereby safely and effectively reducing the health risk of sporadic breast cancer. PMID- 22045028 TI - Mechanistic modelling suggests that the size of preneoplastic lesions is limited by intercellular induction of apoptosis in oncogenically transformed cells. AB - Selective removal of oncogenically transformed cells by apoptosis induced via signalling by surrounding cells has been suggested to represent a natural anticarcinogenic process. To investigate its potential effect in detail, a mechanistic model of this process is proposed. The model is calibrated against in vitro data on apoptosis triggered in transformed cells by defined external inducers as well as through signalling by normal cells under coculture conditions. The model predicts that intercellular induction of apoptosis is capable of balancing the proliferation of oncogenically transformed cells and limiting the size of their populations over long times, even if their proliferation per se were unlimited. Experimental research is desired to verify whether the predicted stable population of transformed cells corresponds to a kind of dormancy during early-stage carcinogenesis (dormant preneoplastic lesions), and how this process relates to other anticarcinogenic mechanisms taking place under in vivo conditions. PMID- 22045029 TI - Relationship between 16 susceptibility loci and colorectal cancer phenotype in 3146 patients. AB - Recent genome-wide association studies have identified single-nucleotide polymorphisms at 16 genetic loci associated with colorectal cancer risk: rs6691170 (1q41), rs10936599 (3q26.2), rs16892766 (8q23.3), rs6983267 (8q24.21), rs10795668 (10p14), rs3802842 (11q23.1), rs11169552 (12q13.13), rs4444235, rs1957636 (14q22.2), rs4779584 (15q13.3), rs9929218 (16q22.1), rs4939827 (18q21.1), rs10411210 (19q13.11), rs961253 and rs4813802 (20p12.3) and rs4925386 (20q13.33). In the present study, we examined whether these variants are preferentially associated with tumour subtype-tumour site, stage, degree of differentiation and microsatellite instability status-in 3146 patients. Several loci showed statistically significant associations with specific phenotypes notably rs6691170 and rs3802842 associated with microsatellite stable rectal disease; rs4779584, rs961253 and rs4813802 associated with microsatellite stable colonic disease and rs4444235 and rs4925386 with microsatellite instability colonic disease. These findings are consistent with pathogenic variants in loci differentially impacting on distinct morphogenetic pathways consistent with aetiologically different risk factors in the development of colorectal cancer. PMID- 22045031 TI - Physiologically based pharmacokinetic model use in risk assessment--Why being published is not enough. AB - A panel of experts in physiologically based pharmacokinetic (PBPK) modeling and relevant quantitative methods was convened to describe and discuss model evaluation criteria, issues, and choices that arise in model application and computational tools for improving model quality for use in human health risk assessments (HHRAs). Although publication of a PBPK model in a peer-reviewed journal is a mark of good science, subsequent evaluation of published models and the supporting computer code is necessary for their consideration for use in HHRAs. Standardized model evaluation criteria and a thorough and efficient review process can reduce the number of review and revision iterations and hence the time needed to prepare a model for application. Efficient and consistent review also allows for rapid identification of needed model modifications to address HHRA-specific issues. This manuscript reports on the workshop where a process and criteria that were created for PBPK model review were discussed along with other issues related to model review and application in HHRA. Other issues include (1) model code availability, portability, and validity; (2) probabilistic (e.g., population-based) PBPK models and critical choices in parameter values to fully characterize population variability; and (3) approaches to integrating PBPK model outputs with other HHRA tools, including benchmark dose modeling. Two specific case study examples are provided to illustrate challenges that were encountered during the review and application process. By considering the frequent challenges encountered in the review and application of PBPK models during the model development phase, scientists may be better able to prepare their models for use in HHRAs. PMID- 22045030 TI - Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. AB - Epidemiological evidence has suggested that consumption of a diet rich in cruciferous vegetables reduces the risk of several types of cancers and chronic degenerative diseases. In particular, broccoli sprouts are a convenient and rich source of the glucosinolate, glucoraphanin, which can release the chemopreventive agent, sulforaphane, an inducer of glutathione S-transferases. Two broccoli sprout-derived beverages, one sulforaphane-rich (SFR) and the other glucoraphanin rich (GRR), were evaluated for pharmacodynamic action in a crossover clinical trial design. Study participants were recruited from the farming community of He Zuo Township, Qidong, China, previously documented to have a high incidence of hepatocellular carcinoma with concomitant exposures to aflatoxin and more recently characterized with exposures to substantive levels of airborne pollutants. Fifty healthy participants were randomized into two treatment arms. The study protocol was as follows: a 5 days run-in period, a 7 days administration of beverage, a 5 days washout period and a 7 days administration of the opposite beverage. Urinary excretion of the mercapturic acids of acrolein, crotonaldehyde, ethylene oxide and benzene were measured both pre- and postinterventions using liquid chromatography tandem mass spectrometry. Statistically significant increases of 20-50% in the levels of excretion of glutathione-derived conjugates of acrolein, crotonaldehyde and benzene were seen in individuals receiving SFR, GRR or both compared with their preintervention baseline values. No significant differences were seen between the effects of SFR versus GRR. Intervention with broccoli sprouts may enhance detoxication of airborne pollutants and attenuate their associated health risks. PMID- 22045033 TI - Selective activation of zebrafish estrogen receptor subtypes by chemicals by using stable reporter gene assay developed in a zebrafish liver cell line. AB - The number of environmental chemical contaminants suspected to act as endocrine disruptor compounds by interacting with estrogen receptor (ER) signaling pathway has been continuously increasing. To study such interaction, the use of stable reporter gene assays is relevant, but species-specific in vitro screening assays are still lacking to address hazard assessment of estrogenic chemicals in aquatic vertebrates. Here, we describe the development of stable reporter gene assays based on stable expression of subtypes of zebrafish ER (zfERalpha, zfERbeta1, and zfERbeta2) coupled to estrogen response element-driven luciferase in a zebrafish liver (ZFL) cell line. The three established cell models, named ZELH-zfERalpha, ZELH-zfERbeta1, and ZELH-zfERbeta2, expressed stable and significant basal luciferase signal, which was induced by 17beta-estradiol (E2) in a sensitive and dose-response manner at EC(50)s of 0.2, 0.03, and 0.05 nM, respectively. In addition, E2 significantly altered cell proliferation in ZELH-zfERalpha and ZELH zfERbeta2 cells, but not in parental ZFL and ZELH-zfERbeta1 cells, suggesting a functionality of these two receptors to modulate endogenous gene expression in the transfected clones. The screening of various xenoestrogens from different classes in the three models resulted in different luciferase response patterns. Natural and synthetic estrogens and 1,1,1-trichloro-2-(2 chlorophenyl)-2-(4 chlorophenyl)ethane were active at lower concentrations in ZELH-zfERbeta1 and ZELH-zfERbeta2 than in ZELH-zfERalpha cells, whereas genistein and zearalenone metabolites as well as three benzophenone derivatives preferentially activated zfERalpha. Altogether, the newly established models provide specific and convenient in vitro tool for comparative assessment of zfERs selective activation by chemicals within ZFL cell context. PMID- 22045034 TI - Transcriptomic concentration-response evaluation of valproic acid, cyproconazole, and hexaconazole in the neural embryonic stem cell test (ESTn). AB - Alternative developmental toxicity assays are urgently needed to reduce animal use in regulatory developmental toxicology. We previously designed an in vitro murine neural embryonic stem cell test (ESTn) as a model for neurodevelopmental toxicity testing (Theunissen et al., 2010). Toxicogenomic approaches have been suggested for incorporation into the ESTn to further increase predictivity and to provide mechanistic insights. Therefore, in this study, using a transcriptomic approach, we investigated the concentration-dependent effects of three known (neuro) developmental toxicants, two triazoles, cyproconazole (CYP) and hexaconazole (HEX), and the anticonvulsant valproic acid (VPA). Compound effects on gene expression during neural differentiation and corresponding regulated gene ontology (GO) terms were identified after 24 h of exposure in relation to morphological changes on day 11 of culture. Concentration-dependent responses on individual gene expression and on biological processes were determined for each compound, providing information on mechanism and concentration-response characteristics. All compounds caused enrichment of the embryonic development process. CYP and VPA but not HEX significantly enriched the neuron development process. Furthermore, specific responses for triazole compounds and VPA were observed within the GO-term sterol metabolic process. The incorporation of transcriptomics in the ESTn was shown to enable detection of effects, which precede morphological changes and provide a more sensitive measure of concentration-dependent effects as compared with classical morphological assessments. Furthermore, mechanistic insight can be instrumental in the extrapolation of effects in the ESTn to human hazard assessment. PMID- 22045035 TI - Pathophysiological modeling of obsessive-compulsive disorder: challenges, and progress. PMID- 22045036 TI - Attention bias modification and the serotonin transporter: personalized treatment implications of gene interactions with learning. PMID- 22045037 TI - Stress and the baby brain. PMID- 22045038 TI - RNA processing in a tiny transcriptome. PMID- 22045039 TI - Efficacy and tolerability of extended release quetiapine fumarate monotherapy in the acute treatment of generalized anxiety disorder: a randomized, placebo controlled and active-controlled study. AB - The main objective of this study was to evaluate efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in generalized anxiety disorder (GAD). This was a 8 week randomized, 2-week follow up, double-blind, placebo-controlled, and active-controlled study. Patients were randomized to quetiapine XR 150 (n=219) or 300 mg/day (n=207); escitalopram, 10 mg/day (n=213); or placebo (n=215). The primary endpoint was the change from randomization at week 8 in Hamilton Anxiety Rating (HAM-A) total score. Week 8 mean HAM-A total score was significantly reduced from randomization with quetiapine XR 150 mg/day (-13.9, P<0.001), 300 mg/day (-12.3, P<0.05) and escitalopram (-12.3, P<0.05) versus placebo (-10.7); significant improvements with quetiapine XR (150 and 300 mg/day) versus placebo (P<0.001) were also shown at day 4. At week 8, significant improvements versus placebo were observed in HAM A psychic [quetiapine XR (both doses) and escitalopram] and somatic (quetiapine XR 150 mg/day and escitalopram) cluster scores and HAM-A response and remission rates (quetiapine XR 150 mg/day). Most common adverse events were dry mouth, somnolence and sedation (quetiapine XR), headache, and nausea (escitalopram). In patients with GAD, quetiapine XR (150 and 300 mg/day) demonstrated significant efficacy at week 8 with symptom improvement as early as day 4. We concluded that quetiapine XR safety and tolerability results were consistent with the known profile of quetiapine. PMID- 22045040 TI - Effects of Lycium barbarum aqueous and ethanol extracts on high-fat-diet induced oxidative stress in rat liver tissue. AB - This study evaluated the protective effects of aqueous extract of Lycium barbarum (LBAE) and ethanol extract of Lycium barbarum (LBEE) on blood lipid levels, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities and liver tissue antioxidant enzyme activities in rats fed a high fat diet (HF). The rats were randomly divided into seven groups of ten rats each and fed a different diet for eight weeks as follows: One group (NC group) was fed a standard diet, one group was fed a high-fat diet (HF group), one group was fed a high-fat diet and orally fed with 20 mg/kg b.w. simvastatin (HF + simvastatin group), and the other group was fed the high fat diet and orally fed with 50 mg/kg b.w. or 100 mg/kg b.w. LBAE (HF + LBAE), or 50 mg/kg b.w. or 100 mg/kg b.w. LBEE (HF + LBEE), respectively. After eight weeks, the HF diet caused deleterious metabolic effects. Rats fed the HF diet alone showed increased hepatocellular enzyme activities in plasma, a significant decline in antioxidant enzyme activities, and elevated liver lipid peroxidation indices. LBAE and LBEE administration significantly reduced liver damage and oxidative changes, and brought back the antioxidants and lipids towards normal levels. These data suggest that these antioxidants protect against toxicity parameters in HF rats. PMID- 22045041 TI - Synthesis and antifungal activity of novel sulfone derivatives containing 1,3,4 oxadiazole moieties. AB - A series of new sulfone compounds containing 1,3,4-oxadiazole moieties were synthesized. The structures of these compounds were confirmed by spectroscopic data (IR, 1H- and 13C-NMR) and elemental analyses. Antifungal tests indicated that all the title compounds exhibited good antifungal activities against eight kinds of plant pathogenic fungi, and some showed superiority over the commercial fungicide hymexazol. Among them, compounds 5d, 5e, 5f, and 5i showed prominent activity against B. cinerea, with determined EC50 values of 5.21 MUg/mL, 8.25 ug/mL, 8.03 ug/mL, and 21.00 ug/mL, respectively. The present work demonstrates that sulfone derivatives such as 5d containing a 1,3,4-oxadiazole moiety can be used as possible lead compounds for the development of potential agrochemicals. PMID- 22045042 TI - Pyrazinecarboxamides as potential elicitors of flavonolignan and flavonoid production in Silybum marianum and Ononis arvensis cultures in vitro. AB - The effect of new synthetic pyrazinecarboxamide derivatives as potential elicitors of flavonolignan and flavonoid production in Silybum marianum and Ononis arvensis cultures in vitro was investigated. Both tested elicitors increased the production of flavonolignans in S. marianum callus and suspension cultures and flavonoids in O. arvensis callus and suspension cultures. Compound I, 5-(2-hydroxybenzoyl)-pyrazine-2-carboxamide, has shown to be an effective elicitor of flavonolignans and taxifoline production in Silybum marianum culture in vitro. The maximum content of silydianin (0.11%) in S. marianum suspension culture was induced by 24 h elicitor application in concentration of 1.159 * 10-3 mol/L. The maximum content of silymarin complex (0.08%) in callus culture of S. marianum was induced by 168 h elicitor application of a concentration 1.159 * 10 4 mol/L, which represents contents of silydianin (0.03%), silychristin (0.01%) and isosilybin A (0.04%) compared with control. All three tested concentrations of compound II, N-(2-bromo-3-methylphenyl)-5-tert-butylpyrazin-2-carboxamide increased the flavonoid production in callus culture of O. arvensis in a statistically significant way. The best elicitation effect of all elicitor concentrations had the weakest c3 concentration (8.36 * 10-6 mol/L) after 168 h time of duration. The maximum content of flavonoids (about 5,900%) in suspension culture of O. arvensis was induced by 48 h application of c3 concentration (8.36 * 10-6 mol/L). PMID- 22045043 TI - The stigma of being a long-term foster carer. AB - Stigma is a powerful social phenomenon with insidious health implications. Understanding stigma as it applies to various populations is imperative for nurses as it enables nurses to enhance individual patient care and nurses are well positioned to influence both social and health care policies which may exacerbate the experience of stigma. This article is a report of a study to explore the experiences of women who provide long-term foster care. Interviews were conducted with 20 women who provided long-term foster care in Australia. Data were coded according to the components of stigma described by Link and Phelan (2001). Findings reveal participants rejected the label of foster carer to avoid the negative stereotype. When unable to conceal their foster carer label, participants experienced social isolation and status loss. Moreover, participants felt marginalized and disempowered within the governing systems. PMID- 22045044 TI - Hypertension: First-in-class agent lowers BP. PMID- 22045045 TI - Imaging of patients with congenital heart disease. AB - Congenital defects most-commonly affect the heart, with an estimated incidence of up to 10 in 1,000 live births. Over the past few decades, mortality has decreased and subsequent survival has increased; approximately 90% of all patients with congenital heart disease (CHD) reach adulthood. Echocardiography is sufficient in most cases for prenatal and postnatal diagnosis of CHD and to plan an intervention, with cardiac MRI and CT providing complementary information on vascular and extracardiac abnormalities. During follow-up, cardiovascular dysfunction is an important cause of reintervention and death. Therefore, routine evaluation of systolic, diastolic, valvular, and vascular function is essential in the care of patients with CHD. Application of echocardiography, cardiac MRI, and CT during follow-up of patients with CHD ideally identifies patients at risk of adverse outcomes, and elucidates the pathophysiological mechanisms that underlie cardiovascular dysfunction. The advent of advanced imaging strategies might further improve the detection of subclinical cardiovascular failure, although further study is required to establish the value of these techniques. Finally, imaging beyond the heart is essential for the complete understanding of the interaction between CHD and noncardiac organ systems, and to extend the success of increased survival to improvements in long-term functional outcome. PMID- 22045046 TI - Can we dramatically reduce the incidence of coronary heart disease? AB - Thrombotic events caused by atherosclerosis are by far the most common cause of death in the world. Advances in treatment have prolonged the life of patients with atherosclerotic disease, but treating individuals with clinically manifest disease will not result in a cure, and will not prevent the majority of such events. This paper explores the possibility that early implementation of a drug based approach to the prevention of atherosclerosis and atherothrombotic events could dramatically reduce the footprint of this disease. Specifically, we consider the potential impact on atherothrombotic events of a population-based, pharmacological approach to lowering serum LDL-cholesterol levels in asymptomatic adults aged 35-50 years. We also consider the feasibility and basic design considerations for a clinical trial to assess the validity of this public health and primary prevention approach. PMID- 22045047 TI - Identification of novel quantitative trait loci for days to ear emergence and flag leaf glaucousness in a bread wheat (Triticum aestivum L.) population adapted to southern Australian conditions. AB - In southern Australia, where the climate is predominantly Mediterranean, achieving the correct flowering time in bread wheat minimizes the impact of in season cyclical and terminal drought. Flag leaf glaucousness has been hypothesized as an important component of drought tolerance but its value and genetic basis in locally adapted germplasm is unknown. From a cross between Kukri and RAC875, a doubled-haploid (DH) population was developed. A genetic linkage map consisting of 456 DArT and SSR markers was used to detect QTL affecting time to ear emergence and Zadoks growth score in seven field experiments. While ear emergence time was similar between the parents, there was significant transgressive segregation in the population. This was the result of segregation for the previously characterized Ppd-D1a and Ppd-B1 photoperiod responsive alleles. QTL of smaller effect were also detected on chromosomes 1A, 4A, 4B, 5A, 5B, 7A and 7B. A novel QTL for flag leaf glaucousness of large, repeatable effect was detected in six field experiments, on chromosome 3A (QW.aww-3A) and accounted for up to 52 percent of genetic variance for this trait. QW.aww-3A was validated under glasshouse conditions in a recombinant inbred line population from the same cross. The genetic basis of time to ear emergence in this population will aid breeders' understanding of phenological adaptation to the local environment. Novel loci identified for flag leaf glaucousness and the wide phenotypic variation within the DH population offers considerable scope to investigate the impact and value of this trait for bread wheat production in southern Australia. PMID- 22045048 TI - ATRP-mediated continuous assembly of polymers for the preparation of nanoscale films. AB - The continuous assembly of polymers (CAP) via atom transfer radical polymerisation (ATRP) is reported as an efficient approach for the preparation of dense, cross-linked, nanoscale engineered films as surface coatings, hollow capsules and replica particles. These films can be reinitiated to allow the preparation of thicker films without loss of film growth efficiency while maintaining similar film density. PMID- 22045049 TI - Hepatitis C virus infection among transmission-prone medical personnel. AB - Hepatitis C virus (HCV)-infected physicians have been reported to infect some of their patients during exposure-prone procedures (EPPs). There is no European consensus on the policy for the prevention of this transmission. To help define an appropriate preventive policy, we determined the prevalence of HCV infection among EPP-performing medical personnel in the Academic Medical Center in Amsterdam, the Netherlands. The prevalence of HCV infection was studied among 729 EPP-performing health care workers. Serum samples, stored after post-hepatitis B virus (HBV) vaccination testing in the years 2000-2009, were tested for HCV antibodies. Repeat reactive samples were confirmed by immunoblot assay and the detection of HCV RNA. The average age of the 729 health care workers was 39 years (range 18-66), suggesting a considerable cumulative occupational exposure to the blood. Nevertheless, only one of the 729 workers (0.14%; 95% confidence interval [CI]: <0.01% to 0.85%) was tested and confirmed to be positive for anti-HCV and positive for HCV RNA, which is comparable to the prevalence of HCV among Amsterdam citizens. Against this background, for the protection of personnel and patients, careful follow-up after needlestick injuries may be sufficient. If a zero-risk approach is desirable and costs are less relevant, the recurrent screening of EPP-performing personnel for HCV is superior to the follow-up of reported occupational exposures. PMID- 22045054 TI - Radical cystectomy in patients over 70 years of age: impact of comorbidity on perioperative morbidity and mortality. AB - PURPOSE: To analyze the impact of comorbidity on the perioperative complication rate after radical cystectomy in patients over 70 year of age. METHODS: Between April 1993 and August 2010, 830 radical cystectomies were performed at our institution. Of the 830 patients, 365 patients (44.0%) were >=70-year-old (median age 74 year). This group of elderly patients was compared with a younger group of 465 patients (56.0% of the whole cohort) aged under 70 year (median 63 year). RESULTS: The group of elderly patients had a significantly higher prevalence of concomitant diseases e.g., hypertension (57.3% vs. 38.5%), coronary heart disease (27.1% vs. 14.8%) and diabetes (25.5% vs. 14.6%). Perioperative complications were significantly more frequent in the elderly group: 31.0% versus 21.5% overall complication rate, P = 0.002. Mortality rate was almost similar in both groups: 0.6% (elderly) versus 0.5% (younger). Within the elderly group, the overall complication rate was significantly higher in patients with an ASA score >=3 (37.0%) than in patients with an ASA score <=2 (25.0%) (P < 0.02). Multivariate logistic regression analysis was used to identify that chronic obstructive lung disease, ASA score and age were independent predictive factors for perioperative complications. CONCLUSIONS: Elderly patients have a higher prevalence of concomitant systemic diseases. Some concomitant diseases can affect surgical outcome after radical cystectomy, particularly the frequency and character of perioperative complications. It is therefore of paramount importance to conduct a comorbidity assessment and preoperative conditioning of each patient, with a special focus on the patient's individual risk factors and age. PMID- 22045055 TI - Cu(ii)- and disulfide bonds-induced stabilization during the guanidine hydrochloride- and thermal-induced denaturation of NAD-glycohydrolase from the venom of Agkistrodon acutus. AB - NAD-glycohydrolase (AA-NADase) from Agkistrodon acutus venom is a unique multicatalytic enzyme with both NADase and AT(D)Pase-like activities. Among all identified NADases, only AA-NADase is a disulfide-linked dimer and contains Cu(2+). Cu(2+) and disulfide bonds are essential for its multicatalytic activity. In this study, the effects of Cu(2+) and disulfide-bonds on guanidine hydrochloride (GdnHCl)- and thermal-induced unfolding of AA-NADase have been investigated by fluorescence, circular dichroism (CD) and differential scanning calorimetry (DSC). Cu(2+) and disulfide bonds not only increase the free energy change during the GdnHCl-induced unfolding as determined by fluorescence, but also increase the overall enthalpy change and the transition temperature during the thermal-induced unfolding as determined by CD and DSC. The slope of the GdnHCl-induced unfolding curve at its midpoint and the heat capacity of thermal induced unfolding are slightly affected by Cu(2+) but significantly decrease after reduction of three disulfide-bonds. This work suggests that Cu(2+) stabilizes the folded state by increasing the enthalpy of unfolding, while disulfide-bonds stabilize the folded state by increasing the enthalpy of unfolding and stabilizing the packing of hydrophobic residues. Thus both Cu(2+) and disulfide bonds play a structural role in its multicatalytic activity. PMID- 22045056 TI - Dietary selenium regulation of transcript abundance of selenoprotein N and selenoprotein W in chicken muscle tissues. AB - Selenium (Se), selenoprotein N (SelN) and selenoprotein W (SelW) play a crucial role in muscle disorders. Se status highly regulates selenoprotein mRNA levels. However, few attempts have been performed on the effect of dietary Se supplementation on muscle SelN and SelW mRNA levels in birds. To investigate the effects of Se on the regulation of SelN and SelW mRNA levels in muscle tissues, one-day-old male chickens were fed either a commercial diet or a Se-supplemented diet containing 1.0, 2.0, 3.0 or 5.0 mg/kg sodium selenite for 90 days. Muscle tissues (breast, flight, thigh, shank and cardiac muscles) were collected and examined for Se content and mRNA levels of SelN and SelW. Moreover, Selenophosphate synthetase-1 (SPS-1) and selenocysteine-synthase (SecS) mRNA levels were analyzed. Significant increases in SelN mRNA levels were obtained in breast, thigh and shank muscles treated with Se, with maximal effects at 3.0 mg Se/kg diet, but 2.0 mg Se/kg diet resulted in peak levels of Sel N mRNA in flight muscles. Changes in SelW mRNA abundance in thigh and shank muscles increased in response to Se supply. After reaching a maximal level, higher Se supplementation led to a reduction in both SelN and SelW mRNAs. However, SelN and SelW mRNA levels displayed a different expression pattern in different skeletal and cardiac muscles. Thus, it suggested that skeletal and cardiac muscles SelN and SelW mRNA levels were highly regulated by Se supplementation and different muscle tissues showed differential sensitivity. Moreover, Se supplementation also regulated the levels of SPS1 and SecS mRNAs. The mRNA levels of SPS1 and SecS were enhanced in the Se supplemented groups. These data indicate that Se regulates the expression of SelN and SelW gene and affect the mRNA levels of SecS and SPS1. PMID- 22045057 TI - Prinzmetal's angina in patients with antiphospholipid syndrome. AB - Antiphospholipid syndrome (APS) is an acquired hypercoagulable disease that is associated with both arterial and venous thrombosis. It is known to cause a spectrum of cardiovascular manifestations including myocardial infarction, stroke, valvular abnormalities, as well as vascular and intracardiac thrombosis. The pathogenesis of myocardial infarction and angina due to APS is thought to be due to coronary thrombosis. Coronary vasospasm without thrombosis can produce myocardial ischemia and chest pain, this is known as Prinzmetal's angina. To our knowledge, Prinzmetal's angina is not known to be associated with APS. In our clinical practice, we came across two cases of APS in which the patients presented with angina and were found to have coronary vasospasm without thrombosis. The finding of these two uncommon diagnoses in multiple individuals raises the possibility that these disorders are associated. PMID- 22045058 TI - The association between different monocyte subsets and coronary collateral development. AB - OBJECTIVES: An increased circulating monocyte count has been found to be related to good collateral development in patients with stable coronary artery disease. Our aim in this study was to determine any possible relationship between the levels of circulating monocyte subsets and coronary collateral development. METHODS: Patients who had greater than 95% stenosis of at least one major coronary artery in their first coronary angiogram were included consecutively in this study. Collateral development was graded as good and poor according to the Cohen-Rentrop method. Blood samples were subjected to cytometric analysis for the determination of monocyte subsets, CD14++CD16- and CD14+CD16+ monocytes. RESULTS: Out of 105 patients, 55 had good and 50 had poor coronary collateral development. When the baseline characteristics were compared, the monocyte count was significantly higher in the good collateral group (517+/-151 vs. 396+/-109/mm3, P<0.001). Cytometric analysis indicated that CD14++CD16- levels were significantly higher in the good collateral group (422+/-147 vs. 298+/-105/mm3, P<0.001). CD14+CD16+ cells did not differ between groups (80+/-29 vs. 84+/ 29/mm3, P=0.41). When multivariate analysis was performed, increased CD14++CD16- levels were still significantly associated with good collateral development [odds ratio: 1.009 (1.005-1.014), P<0.001]. CONCLUSION: Our present results are the first to show a significant association between increased circulating CD14++CD16- monocyte levels and good coronary collateral development. Further studies are needed to better understand the relationship between different subsets of monocytes and collateralization. PMID- 22045059 TI - Cloning and expression analysis of piRNA-like RNAs: adult testis-specific small RNAs in chicken. AB - Many small RNAs have been cloned from animal gonads, for example, endogenous small interfering RNAs (endo-siRNAs) were found in oocytes and piwi-interacting RNAs (piRNAs) were found in testis. Gallus gallus (chicken) is an important model organism, but few small RNAs have been identified from its gonads. In this study, we isolated and cloned 156 small RNAs from adult chicken testes. Since there is a reasonably even distribution from 22 to 33 nt, these small RNAs are slightly longer than miRNAs and endo-siRNAs. Genome mapping indicated that these small RNAs were derived from intergenic regions, exons, introns, and repetitive elements including chicken repeat 1, long terminal repeats, and simple repeats. Since they are similar with piRNAs, we named them piRNA-like RNAs (pil-RNAs). Northern blotting of 16 selected sequences showed that nine are specifically expressed in the adult testis. The vast majority of these pil-RNAs are poorly conserved between species, suggesting that they are unique to the adult chicken testis. Further analysis of the cloned pil-RNAs will improve our understanding of the function of small RNAs in animal gonad development. PMID- 22045060 TI - Quaternary structural parameters of the congenital cataract causing mutants of alphaA-crystallin. AB - Pediatric cataract of the congenital type is the most common form of childhood blindness and it is clinically and genetically heterogeneous. Mutations in 22 different genes have been identified to be associated with congenital cataracts, and among them, eight mutants belong to alphaA-crystallin. To explain how mutations in alphaA-crystallin lead to the development of cataract, quaternary structural parameters, and chaperone function have been investigated in alphaA-wt and in the following mutants: R12C, R21L, R21W, R49C, R54C, R116C, and R116H. Average molar mass, mass at the RI peak, mass across the peak, hydrodynamic radius (R(h)), and polydispersity index (PDI) were determined by dynamic light scattering measurements. The average molar mass and mass across the peak showed major increase in R116C and R116H, moderate increase in R12C, R21W, and R54C, and no increase in R21L and R49C as compared to alphaA-wt. PDI and R(h) values were significantly increased only in R116C and R116H. Significant secondary structural changes, as determined by CD measurements, were seen in R21W, R21L, R116C, and R116H, and tertiary structural changes were evident in R21W, R54C, R116C, and R116H. Non-reducing SDS-PAGE has shown the presence of dimers presumably formed by inter-polypeptide disulfide bonds. Chaperone activity, as measured with ADH as the target protein, appeared normal in R49C and R54C, while R12C, R21L, and R21W showed moderate loss and R116C and R116H showed significant loss. Although a specific change in the alphaA-crystallin behavior that is common to all the mutants was not evident, each mutant showed one or more perturbation as the end effect that leads to cataract. PMID- 22045061 TI - MicroRNA- 1 represses Cx43 expression in viral myocarditis. AB - MicroRNAs (miRNAs) are increasingly reported to have important roles in diverse biological and pathological processes. Changes in abundance of muscle-specific microRNA, miR-1, have been implicated in cardiac disease, including arrhythmia and heart failure. However, the specific molecular targets and cellular mechanisms involved in the miR-1 function in the heart are only beginning to emerge. In this study, we investigated miR-1 expression and its potential role in the mouse model of viral myocarditis (VMC). The expression levels of miR-1 and its target gene Connexin 43 (Cx43) were measured by real-time PCR and western blotting, respectively. The miR-1 expression levels were significantly increased in cardiac myocytes from VMC mice in comparison with control samples (relative expression: 10 +/- 2.5 vs. 31 +/- 7.6, P < 0.05). Among the target genes of miR 1, the expression Cx43 protein was significantly reduced in such mice while there was no significant difference in the its mRNA levels. Our results revealed an inverse correlation between miR-1 levels and Cx43 protein expression in VMC samples. Using a bioinformatics-based approach, we found two identical potential binding sites were found in mouse miR-1 and Cx43 3'- untranslated region, this confirms a possible regulatory role of miR-1. In cultured, miRNA transfected myocardial cells, we show overexpression of miR-1 accompanied by a decrease in Cx43 protein's expression. There was only a slight (not statistically significant) drop in Cx43 mRNA levels. Our results indicate that miR-1 is involved in VMC via post-transcriptional repression of Cx43, and might constitute potentially valuable data for the development of a new approach in the treatment of this disease. PMID- 22045062 TI - Elevated expression of RGS19 impairs the responsiveness of stress-activated protein kinases to serum. AB - Regulators of G protein signaling (RGS proteins) serve as GTPase activating proteins for the signal transducing Galpha subunits. RGS19, also known as Galpha interacting protein (GAIP), has been shown to subserve other functions such as the regulation of macroautophagy and growth factor signaling. We have recently demonstrated that the expression of RGS19 in human embryonic kidney (HEK) 293 cells resulted in the disruption of serum-induced mitogenic response along the classical Ras/Raf/MEK/ERK pathway. Here, we further examined the effect of RGS19 expression on the stress-activated protein kinases (SAPKs). Both c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) became non responsive to serum in 293/RGS19 cells, yet the two SAPKs responded to UV irradiation or osmotic stress induced by sorbitol. Kinases upstream of JNK and p38 MAPK, including MKK3/6, MKK4, and MLK3, also failed to respond to serum stimulation in 293/RGS19 cells. Serum-induced activation of the small GTPases Rac1 and Cdc42 was similarly suppressed in these cells. Our results indicate that elevated expression of RGS19 can severely disrupt the regulation of MAPKs by small GTPases. PMID- 22045063 TI - Molecular assessment of c-H-ras p21 expression in Helicobacter pylori-mediated gastric carcinogenesis. AB - Helicobacter pylori (H. pylori) infection plays a significant role in causing gastric cancer; the exact molecular mechanisms of gastric carcinogenesis have not yet been fully determined. Therefore, this study was planned to examine the role of c-H-ras p21 expression in H. pylori infection at different stages of disease progression from precursor lesions to gastric carcinoma. This study was carried out in 200 patients, consisting of normal gastric mucosa (n = 20), mucosa with chronic gastritis (n = 63), intestinal metaplasia (n = 20), dysplasia (n = 11), and gastric adenocarcinoma (n = 86), in which the H. pylori status have been analysed. The expression of c-H-ras p21 was studied at mRNA as well as protein level using RT-PCR and western blotting, respectively. The localization of c-H ras p21 was also studied semiquantitatively by immunohistochemistry. The RT-PCR and western blotting results of c-H-ras p21 mRNA and protein expressions were significantly increased in chronic gastritis, intestinal metaplasia, dysplasia, and gastric adenocarcinoma patients, respectively. Immunohistochemical study also showed the increased expression of c-H-ras p21 in the similar way. Overexpression of c-H-ras p21 might be due to H-ras mutation at codon 12 of ras gene family in H. pylori infection. The rate of expression of ras p21 was higher in the H. pylori-infected precursor lesions, chronic gastritis 49/56 (87.5%), intestinal metaplasia 16/17 (94%), and dysplasia 9/11(82%) whereas in the case of H. pylori negative cases these groups, show 12.5, 5.9, and 18.2%, respectively. The data suggested that H. pylori infection may increase the expression of c-H-ras p21 early in the process of gastric carcinogenesis. PMID- 22045064 TI - Activity of tumor necrosis factor-alpha blocked by phytoglycoprotein (38 kDa) at initiation stage in N-nitrosodiethylamine-induced ICR mice. AB - Hepatocellular carcinoma is becoming one of the most prominent types of cancer in the world. Recently, from Styrax japonica Siebold et al. Zuccarini (SJSZ), we isolated a glycoprotein which consists of carbohydrate moiety (52.64%) and protein moiety (42.35%). We evaluated whether SJSZ glycoprotein prevents hepatocarcinogenesis induced by N-nitrosodiethylamine (DEN). The purpose of this study was to evaluate the effect of SJSZ glycoprotein in DEN-induced hepatocarcinogenesis in ICR mice. To know chemopreventive effect of SJSZ glycoprotein on hepatocarcinogenesis, ICR mice were intraperitoneally injected with N-nitrosodiethylamine (DEN, 10 mg/kg) for 7 weeks. After sacrifice, we evaluated indicators of liver tissue damage [the activities of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and thiobarbituric acid reactive substances (TBARS)], antioxidative enzymes [activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], and initiating hepatocarcinogenic indicator [heat shock protein (HSP) 27 and 70] and hepatocarcinogenic signals [protein kinase C (PKC), extracellular signal regulating kinase (ERK) 1/2, nuclear factor (NF)-kappaB (p50 and p65) and tumor necrosis factor-alpha (TNF-alpha)] using biochemical methods, immunoblot analysis, and RT-PCR. The results obtained from this study revealed that SJSZ glycoprotein (10 mg/kg, BW) decreased the levels of LDH, ALT, and TBARS, whereas the activities of SOD, GPx, and CAT increased in the DEN-induced ICR mice. With respect to the hepatocarcinogenic indicator and hepatocarcinogenic signals, HSP27, HSP70, PKC, ERK1/2, NF-kappaB (p50 and p65), and TNF-alpha, activity decreased. Hence, SJSZ glycoprotein might prevent expression of HSP27 and HSP70 by DEN. PMID- 22045065 TI - Chronic mild hyperhomocysteinemia alters ectonucleotidase activities and gene expression of ecto-5'-nucleotidase/CD73 in rat lymphocytes. AB - Since mild hyperhomocysteinemia is a risk factor for cardiovascular and cerebral diseases and extracellular nucleotides/nucleosides, which are controlled by the enzymatic action of ectonucleotidases, can induce an immune response, in the present study, we investigated the effect of chronic mild hyperhomocysteinemia on ectonucleotidase activities and expression in lymphocytes from mesenteric lymph nodes and serum of adult rats. For the chronic chemically induced mild hyperhomocysteinemia, Hcy (0.03 MUmol/g of body weight) or saline (control) were administered subcutaneously from the 30th to the 60th day of life. Results showed that homocysteine significantly decreased ATP, ADP, and AMP hydrolysis in lymphocytes of adult rats. E-NTPDases transcriptions were not affected, while the ecto-5'-nucleotidase transcription was significantly decreased in mesenteric lymph nodes of hyperhomocysteinemic rats. ATP, ADP, and AMP hydrolysis were not affected by homocysteine in rat serum. Our findings suggest that Hcy in levels similar to considered risk factor to development of vascular diseases modulates the ectonucleotidases, which could lead to a pro-inflammatory status. PMID- 22045066 TI - Molecular metabolic fingerprinting approach to investigate the effects of borneol on metabolic alterations in the liver of nitric oxide deficient hypertensive rats. AB - Hypertension is one of the major risk factor that underlie a wide range of cardiovascular irregularities which causes functional and metabolic alterations in vascular system and major organs. Nitric oxide is the central regulator of the vascular system and its deficiency leads to increased blood pressure and metabolic alterations in liver. Fourier transform infrared spectroscopy (FTIR) is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds with in the sample that absorbs it and different samples contain diverse configurations of molecular bonds. Both wavenumber and area of the vibrational spectra can be used to explore the qualitative and quantitative constituent of macromolecules. In this study, we intended to evaluate the protective role of borneol, a natural terpene on liver metabolism in a nitric oxide deficient model of hypertension through interpretation of FTIR spectral information. Results demonstrate that FTIR can successfully indicate the molecular changes that occur in all groups. The over all findings demonstrate that in nitric oxide deficient animal model of hypertension, the liver metabolic program is altered through increasing the structural modification in proteins and triglycerides, and quantitative alteration in proteins, lipids, and glycogen. All the above mentioned modifications were protected by borneol in liver and showed its ability to exert a novel defensive action on hepatic metabolism. PMID- 22045067 TI - The new Knee Society Knee Scoring System. PMID- 22045068 TI - Case report: bilateral proximal epiphyseal clavicular stress-related lesions in a male gymnast. AB - BACKGROUND: Stress lesions of the upper extremity are relatively uncommon, and physeal stress lesions of the clavicle are rare. We present a case of bilateral physeal stress-related lesions of the proximal clavicular growth plate near the sternoclavicular joint in an adolescent male gymnast. CASE DESCRIPTION: A 13-year old gymnast presented with a 3-week history of insidious onset of pain in the proximal clavicular area of his left shoulder. He had no pain at rest or at night. He recently had added a new maneuver to his routine. His radiographs were normal, but further study with CT scanning confirmed a stress lesion of his proximal clavicular physis. The lesion healed with time, and he returned to gymnastics with no symptoms. Approximately 5 months after the initial symptoms on the left side, he felt a pop and immediate pain in his right sternoclavicular joint area while doing a routine. Imaging revealed a chronic stress lesion of the proximal physis similar to that of the other side. The patient achieved healing with rest and returned to gymnastics with no limitations. LITERATURE REVIEW: Physeal stress-related lesions of the proximal clavicular physis have not been reported in the literature. PURPOSE AND CLINICAL RELEVANCE: Medial clavicle pain in adolescent gymnasts may be secondary to stress-related lesions of the proximal clavicular growth plate. Such lesions are rare. PMID- 22045069 TI - Aseptic failure: how does the Compress((r)) implant compare to cemented stems? AB - BACKGROUND: Failure of endoprosthetic reconstruction with conventional stems due to aseptic loosening remains a challenge for maintenance of limb integrity and function. The Compress((r)) implant (Biomet Inc, Warsaw, IN, USA) attempts to avoid aseptic failure by means of a unique technologic innovation. Though the existing literature suggests survivorship of Compress((r)) and stemmed implants is similar in the short term, studies are limited by population size and followup duration. QUESTIONS/PURPOSES: We therefore compared (1) the rate of aseptic failure between Compress((r)) and cemented intramedullary stems and (2) evaluated the overall intermediate-term implant survivorship. METHODS: We reviewed 26 patients with Compress((r)) implants and 26 matched patients with cemented intramedullary stems. The patients were operated on over a 3-year period. Analysis focused on factors related to implant survival, including age, sex, diagnosis, infection, aseptic loosening, local recurrence, and fracture. Minimum followup was 0.32 years (average, 6.2 years; range, 0.32-9.2 years). RESULTS: Aseptic failure occurred in one (3.8%) patient with a Compress((r)) implant and three (11.5%) patients with cemented intramedullary stems. The 5-year implant survival rate was 83.5% in the Compress((r)) group and 66.6% in the cemented intramedullary stem group. CONCLUSIONS: The Compress((r)) implant continues to be a reliable option for distal femoral limb salvage surgery. Data regarding aseptic failure is encouraging, with equivalent survivorship against cemented endoprosthetic replacement at intermediate-term followup. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22045070 TI - High incidence of migration with poor initial fixation of the Accolade stem. AB - BACKGROUND: Numerous cementless femoral stem design variations are in clinical use. Because initial implant instability and micromotion are associated with aseptic loosening of the femoral component, migration analysis provides an early assessment of implant survivorship. QUESTIONS/PURPOSES: We determined the (1) migration pattern of the Accolade cementless femoral stem; (2) clinical factors predisposing to stem migration; (3) self-reported patient outcomes; and (4) our current rate of aseptic stem loosening. METHODS: We retrospectively analyzed 81 femoral stems for aseptic migration using Ein-Bild-Roentgen-Analyse-femoral component analysis. Postoperatively, patients completed the WOMAC and SF-12 questionnaires. We assessed radiographic factors potentially associated with subsidence: indices of bone shape and quality, canal fill of the implant, and radiographic signs of loosening. Minimum followup was 24 months (mean, 29 months; range, 24-48 months). RESULTS: The average subsidence at 24 months was 1.3 mm (range, 0-1.5 mm). In the first 2 years, 36% of stems subsided more than 1.5 mm. Large stem size was associated with subsidence. Radiolucent lines (> 1.5 mm in three zones) were present in 10% of stems and associated with lower questionnaire scores. The 5-year survivorship for aseptic loosening of the 367 stems was 97% with revision as end point and 95% for radiographic failure. CONCLUSIONS: The high incidence of migration and stems with radiographic failure raises concerns about patient clinical function and long-term survivorship of this stem design. This migration pattern may be due to poor initial stability with a subsequent lack of osseointegration. Our results differ from radiographic findings and clinical durability of other similar cementless stem designs. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 22045071 TI - Causes of failure of ceramic-on-ceramic and metal-on-metal hip arthroplasties. AB - BACKGROUND: Few large series of hard bearing surfaces have reported on reasons for early failure. A number of unique mechanisms of failure, including fracture, squeaking, and adverse tissue reactions, have been reported with these hard bearing surfaces. However, the incidence varies among the published studies. QUESTIONS/PURPOSES: To confirm the incidences, we identified the etiologies of early failures of hard-on-hard bearing surfaces for ceramic-on-ceramic and metal on-metal THAs. METHODS: We retrospectively reviewed records of 2907 THAs with hard-on-hard bearing surfaces implanted between 1996 and 2009; 1697 (58%) had ceramic-on-ceramic and 1210 (42%) had metal-on-metal bearing surfaces. We recorded bearing-related complications and compared them to nonspecific reasons for revision THA. The minimum followup of the ceramic-on-ceramic and metal-on metal cohorts was 6 months (mean, 48 months; range, 6-97 months) and 24 months (mean, 60 months; range, 24-178 months), respectively. RESULTS: The overall revision rate for ceramic-on-ceramic THA was 2.2% (38 of 1697), with aseptic loosening accounting for 55% of revisions (femur or acetabulum). The bearing accounted for 13% of the revisions in the ceramic-on-ceramic THA cohort. The overall metal-on-metal revision rate was 5.4% (65 of 1210), 17 involving adverse tissue reactions related to the metal-on-metal bearing surface (17 of 1210, 1.4% of cases; 17 of 65, 26% of revisions). CONCLUSIONS: Twenty-six percent of the revisions from metal-on-metal and 13% of ceramic-on ceramic were bearing related. The overall short- to medium-term revision rate was 2.2% and 5.4% for ceramic-on ceramic and metal-on-metal, respectively. The most common etiology of failure was loosening of the femoral or acetabular components. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence. PMID- 22045072 TI - Incidence of deep vein thrombosis and pulmonary embolism after Achilles tendon rupture. AB - BACKGROUND: The use of venous thromboembolism prophylaxis after an Achilles rupture is controversial. The rates of reported deep vein thrombosis (DVT) range from 6.3% to 34%. There is no agreement regarding prophylactic therapy after an Achilles tendon rupture. QUESTIONS/PURPOSES: We determined the overall risk of DVT and pulmonary embolism (PE) after an Achilles tendon rupture and identified potential risk factors including surgery. PATIENTS AND METHODS: We retrospectively reviewed a large healthcare management organization database and identified 1172 patients who had Achilles tendon ruptures. None of the patients routinely received anticoagulation. Patients were stratified into surgical versus nonsurgical group, age older than 40 years, history of congestive heart failure, previous history of DVT or PE, and BMI greater than 30. A patient was considered to have symptomatic DVT or PE related to the Achilles tendon rupture if diagnosed within 3 months from the injury or surgery. We used a multivariable analysis to identify risk factors. RESULTS: The overall rates for DVT and PE after Achilles tendon ruptures were 0.43% and 0.34%, respectively. Age older than 40 years, congestive heart failure, history of DVT or PE, obesity, and whether a patient had surgery did not predict occurrence of DVT or PE. CONCLUSION: We found the overall incidence of symptomatic DVT and PE to be low after an Achilles tendon rupture and believe routine use of anticoagulation might be unwarranted. PMID- 22045073 TI - Pilot study of a new posterior chamber phakic intraocular lens (epi.lens) for high myopia. AB - PURPOSE: To report the first safety and efficacy results of a new posterior chamber phakic intraocular lens (PIOL) (Epi.Lens, Acri.Tec/Carl Zeiss Meditec) implanted in the ciliary sulcus to correct high myopia. METHODS: The Epi.Lens was implanted for the first time in 48 consecutive eyes of 25 patients in an ongoing two-center clinical study. Pre- and postoperative manifest refraction, uncorrected (UDVA) and corrected distance visual acuity (CDVA), intraocular pressure, slit-lamp and funduscopic examination, and ultrasound biomicroscopy were evaluated. Follow-up examinations were performed at 1, 3, 6, 12, and 24 months postoperatively. For each patient, the latest follow-up data were considered. RESULTS: The study cohort consisted of highly myopic patients with mean preoperative manifest refraction spherical equivalent of -9.90 +/- 2.53 D, which was reduced to -0.26 +/- 0.84 D postoperatively. Two (4.2%) eyes lost one line of CDVA postoperatively, whereas 19 (40%) met and 27 (56%) eyes exceeded preoperative CDVA values, thus improving mean CDVA from 0.83 +/- 0.30 to 1.03 +/- 0.26. Mean postoperative UDVA (0.85 +/- 0.37) was similar to preoperative CDVA (0.83 +/- 0.30). When considering all eyes with good visual potential (preoperative CDVA >= 1.00 [20/20] [n=25]), 20 (80%) achieved postoperative UDVA >= 1.00 (20/20), and 24 (96%) achieved UDVA >= 0.80 (20/25). One lens with a small diameter showed contact of the Epi.Lens and crystalline lens with subsequent slight anterior subcapsular cataract; however, CDVA was 1.00 (20/20) at last follow-up 2 years postoperatively. CONCLUSIONS: The results of this Epi.Lens pilot study demonstrate good safety and efficacy. The preliminary data are encouraging, and longer follow-up results are anticipated. PMID- 22045074 TI - 2D sheet-like architectures constructed from main-group metal ions, 4,4'-bpno and 1,2-alternate p-sulfonatothiacalix[4]arene. AB - Two novel 2D sheet-like complexes 1 and 2 have been prepared by reaction of p sulfonatothiacalix[4]arene (TC4AS) with main-group metal ions (lead(II) or barium(II)) and 4,4'-bipyridine-N,N'-dioxide (4,4'-bpno). In both complexes 1 and 2, TC4AS molecules prefer 1,2-alternate conformation, forming 2D sheet-like layers in the presence of divalent ions and 4,4'-bpno ligand. The layers extend to 3D architectures via strong hydrogen bonding interactions. In addition, complexes 1 and 2 are thermally stable up to ca. 335 and 305 degrees C, respectively. It seems that the strong hydrogen bonds between the sheet-like layers impart the extraordinarily high degrees of stability to the structures. Further analysis indicates that complexes 1 and 2 are significantly different: (a) the divalent ions have different coordination environments due to the nature of the different ions; (b) TC4AS within complexes 1 and 2 connects to four Pb(II) or six Ba(II) ions, respectively; (c) 4,4'-bpno shows different connection modes; (d) in the solid state, complex 1 exhibits intense orange luminescence with triexponential decays, while complex 2 does not exhibit any obvious luminescence at cryogenic temperatures. PMID- 22045075 TI - The impact of iso-osmolar contrast use in emergent percutaneous coronary intervention for ST-segment elevation myocardial infarction. AB - The incidence of contrast-induced nephropathy (CIN) in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) was previously reported to be as high as 19%. Iso-osmolar contrast has frequently been used for populations at high risk for CIN, but a recent meta analysis did not show a significant benefit of using iso-osmolar contrast in preventing CIN. The aim of our study is to evaluate the impact of iso-osmolar contrast use in patients undergoing emergent PCI. We performed a retrospective analysis of patients who underwent primary and rescue PCI for STEMI. The PCI strategy, including the contrast choice, was left at the discretion of the operator. CIN was defined as an increase in creatinine of more than 0.5 mg or 25% from the baseline within 72 hours. Among 212 patients, CIN was seen in 33 patients (16%). Patients who received iso-osmolar contrast were older, and included more patients at risk for CIN. The incidence of CIN was 14% in the low osmolar contrast group and 17% in the iso-osmolar contrast group (P=.799). After logistic regression analysis, CIN was seen more frequently in patients who had lower ejection fraction, post-PCI TIMI flow <3, and lower hemoglobin. The use of iso-osmolar contrast was not associated with a lower incidence of CIN in patients undergoing emergent PCI for STEMI. PMID- 22045076 TI - Preventing contrast-induced nephropathy in patients undergoing primary PCI. PMID- 22045077 TI - Comparison of the resource utilization between simultaneous strategy and staged strategy to treat two-vessel coronary artery disease by percutaneous coronary intervention. AB - OBJECTIVES: The purpose of this study was to compare medical resource use, such as total device cost, total contrast volume, and total fluoroscopy time between the staged and simultaneous strategies for treating two-vessel disease (2VD) by percutaneous coronary intervention (PCI). BACKGROUND: 2VD can be treated by the staged strategy or the simultaneous strategy. Compared to the staged strategy, the simultaneous strategy may reduce medical resource use. METHODS: We identified a staged group (138 patients) and simultaneous group (62 patients) from our PCI database between January 1, 2008 and December 31, 2010. Total PCI device cost, total contrast volume, and total fluoroscopy time were compared between the two groups. RESULTS: Total costs for the staged group and the simultaneous group given in United States dollars were $21,289 +/- 5633 and $16,571 +/- 5530, respectively (P<.0001). Total contrast volumes for the staged group and the simultaneous group were 299 +/- 79 mL and 194 +/- 62 mL, respectively (P<.0001). Total fluoroscopy times for the staged group and the simultaneous group were 60 +/- 27 minutes and 40 +/- 15 minutes, respectively (P<.0001). In multivariate analysis, the simultaneous strategy was significantly associated with low cost, small contrast volume, and short fluoroscopy time even after controlling for age, sex, acute coronary syndrome, and lesion complexity. CONCLUSIONS: Compared to the staged strategy to treat 2VD by PCI, the simultaneous strategy reduced medical resource use, i.e., total device cost, total contrast volume, and total fluoroscopy time. PMID- 22045078 TI - Dual-source CT angiography for detection and quantification of in-stent restenosis in the left main coronary artery: comparison with intracoronary ultrasound and coronary angiography. AB - OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of dual source computed tomography coronary angiography (CTCA) compared to coronary angiography (CAG) and intravascular ultrasound (IVUS) for detection and quantification of in-stent restenosis after left main (LM) coronary artery stenting. MATERIALS AND METHODS: Fifty-one patients with percutaneous coronary intervention of the LM were prospectively evaluated. Thirty-four of them underwent 56 complete follow-up examinations (CTCA, CAG, and IVUS as gold standard examination) that focused on detection and quantification of restenosis. RESULTS: Sensitivity, specificity, and positive and negative predictive values were 100%, 94%, 50%, and 100% for CAG, respectively, and 100%, 74%, 18%, and 100% for CTCA, respectively. There was a correlation between the minimal luminal areas (MLA) measured by CTCA and IVUS (r = 0.63; P<.01). A Bland-Altman analysis showed that the MLA measured by CTCA was underestimated (mean difference, 2.14 +/- 2.24 mm2). CONCLUSION: Dual-source CTCA has a high negative predictive value and might be considered a less invasive alternative to CAG for exclusion of LM in-stent restenosis. However, there was only a moderate correlation between the MLA measurements by IVUS and CTCA in the stented LMs. Moreover, the present results suggest a systematic underestimation of MLAs measured by CTCA. Therefore, finding of any restenosis according to CTCA should be re-evaluated by CAG or, better, by subsequent IVUS. PMID- 22045079 TI - Stent evaluation by coronary computed tomographic angiography and expert consensus documents. PMID- 22045080 TI - A high dose of adenosine to induce transient asystole for valvuloplasty in patients undergoing transcatheter aortic valve implantation (TAVI): is it a valid alternative to rapid pacing? A prospective pilot study. AB - BACKGROUND: Rapid right ventricular pacing (RRVP) at rates above 200 beats/minute is used to suppress cardiac output during balloon aortic valvuloplasty (BAV) in transcatheter aortic valve replacement (TAVI) patients. A risk of inducing myocardial ischemia with RRVP remains, especially in patients with left ventricular dysfunction. Alternatively, a transient cardiac arrest can be achieved with administration of adenosine. METHODS: The primary endpoint was successful valvuloplasty defined by complete balloon inflation and deflation across aortic valve during the transient asystole induced by adenosine. Secondary endpoints were defined as the failure of adenosine to induce asystole, the incidence of ventricular ectopic beats (VEB) during balloon inflation or deflation, and balloon displacement. RESULTS: From November 2010 to January 2011, twenty consecutive patients who underwent TAVI were included. A balloon for valvuloplasty was positioned across the aortic valve. A low-dose (24 mg, n = 10) or high-dose (36 mg, n = 10) bolus of adenosine was administrated. A single bolus of adenosine-induced atrioventricular (AV) block (mean duration, 18.6 +/- 6.6 seconds) followed by cardiac asystole in 16 patients (80%) (low-dose, n = 9). A successful BAV was achieved in 12 patients (60%) (low-dose, n = 8). Adenosine induced only bradycardia in 4 patients (20%) (low-dose, n = 1). A burst of VEB during BAV occurred in all patients. Balloon displacement occurred in 6 patients (37.5%). CONCLUSION: BAV after administration of adenosine is feasible, safe, and may represent an option for high-risk TAVI patients in whom RRVP might not be well tolerated. The occurrence of ventricular ectopic contractions triggered by balloon inflation and deflations accounts for balloon displacement and crossover to RRVP. PMID- 22045081 TI - Utility of adenosine sequelae in primer balloon aortic valvuloplasty. PMID- 22045082 TI - Simultaneous inflation of two drug-eluting balloons for the treatment of coronary bifurcation restenosis: a concept series. AB - Coronary bifurcation restenoses are especially challenging lesions to treat. In this report, four cases are described in which an innovative approach consisting of the simultaneous inflation of two drug-eluting balloons has been successfully applied to treat different kinds of bifurcation restenoses following both provisional and complex stenting strategies. These selected cases illustrate the concept and the advantages of a kissing drug-eluting balloon strategy for the treatment of virtually any kind of bifurcation restenosis. PMID- 22045083 TI - Transradial percutaneous coronary intervention in patients requiring circulatory assist devices. PMID- 22045084 TI - Use of embolic capture angioplasty for the treatment of occluded superficial femoral artery segments. AB - Treatment of peripheral chronic total occlusion (CTO) is one of the most challenging lesion subsets in peripheral revascularization. Advanced wire technology, novel re-entry catheters and imaging techniques help in crossing such lesions. Subintimal dissection using blunt microdissection devices along with true lumen reentry techniques have added to the success rates of treating peripheral CTOs. After crossing the occlusion, balloon angioplasty and the placement of self-expanding nitinol stents are usually performed. Peripheral embolization is a known complication of peripheral artery interventions, leading to significant lower-extremity ischemia and complications. Such interventions of peripheral CTOs have been shown to have higher rates of distal embolization. Though no dedicated distal embolic protection strategies are currently available for lower-extremity interventions, use of debris capture angioplasty balloon (ProteusTM) may be a feasible alternative. We report 3 cases where this device has been used during recanalization of peripheral CTOs. PMID- 22045085 TI - Major bleeding in acute coronary syndromes. AB - Treatment of acute coronary syndrome has been based on the prevention of ischemic complications by means of antithrombotic therapy and invasive strategies. The desired reduction reached in the recurrence of ischemic events reveals its price, an increase in the occurrence of major bleeding. Initially tolerated as a benign complication, it is now shown to be an important predictor of mortality. Greater attention dedicated to the prognostic impact of bleeding is recent, motivated by the development of new antithrombotic agents. Detailed analysis of the risk factors for myocardial infarction or bleeding is an important issue and allows institution of individualized approach. PMID- 22045086 TI - American health care, and notably cardiovascular care, cannot be defined by WHO mortality rankings. PMID- 22045087 TI - Proximal right coronary artery diverticulum resulting in recurrent distal embolization. AB - This is a case of a right coronary artery (RCA) diverticulum. We highlight the complications of distal embolization and recurrent myocardial infarctions (MI), and the successful closure with a covered stent. A 33-year-old Khat user experienced non-ST elevation MI (non-STEMI) 3 times over 2 years. His first cardiac catheterization showed a proximal RCA ulceration. The last catheterization revealed a proximal RCA diverticulum containing a thrombus, and a thrombus at the distal PDA. A covered Jomed(r) stent (Jomed International AB) was placed into the proximal RCA, closing the diverticulum, and preventing future embolizations. Patient's atherosclerotic ulceration led to diverticular disease that resulted in blood flow stasis, thrombi, distal embolization, and repeat acute coronary events. PMID- 22045088 TI - Endovascular treatment of residual type A aortic dissection preserving patency of supra-aortic vessels by implantation of the Djumbodis(r) system. No more surgery for the aortic arch? AB - A persistent distal false lumen perfusion--residual type A aortic dissection--is found in 50% to 100% of patients following ascending aorta replacement. Complications of persistent or newly developed dissection of the distal aorta are often fatal and require reoperation, leading to a higher morbidity and mortality rate for these patients than with primary surgery. Thus, many efforts have been done to treat this aortic disease by an endovascular approach. Unfortunately, patency of the supra-aortic vessel still remains an unresolved issue. The present report describes the case of a patient with a residual type A aortic dissection persisting after ascending aorta replacement, successfully treated by implantation of a new endovascular device, the Djumbodis(r) Dissection System, a bare stent with sufficiently large mesh to join the dissected layers without occluding main vital branches such as supra-aortic arteries. PMID- 22045089 TI - GuideLiner catheter facilitated PCI--a novel device with multiple applications. AB - OBJECTIVE: The GuideLiner catheter (Vascular Solutions, Inc.) is a monorail guiding catheter extension that serves to facilitate stent delivery and is approved for providing extra support and coaxial guide engagement. The objective of this manuscript is to familiarize interventionalists with this new device, describe its versatile uses, and its limitations with case-based examples. BACKGROUND: Failure of stent delivery is responsible for 5% of procedural failures in coronary interventions in the current era. Different techniques to enhance guiding catheter support and facilitate device delivery have been described. These include use of buddy wires, anchoring balloons at different locations for extra support for device delivery, and even rotational atherectomy in the most calcified lesions. METHODS: The database of coronary interventions at Banner Good Samaritan Medical Center was queried for use of the GuideLiner catheter and stents. The angiograms of all those cases were reviewed and selections of cases highlighting different uses of the catheter were chosen for inclusion in this manuscript. RESULTS: All potential uses of the GuideLiner catheter are described in this manuscript. Nuances about use and tips and tricks related to the device are also discussed in the case examples. CONCLUSIONS: The manuscript provides a complete summary of the different uses and limitations of the catheter and its contemporary role in modern day coronary intervention. PMID- 22045090 TI - Successful treatment of a late presentation exercise-induced spontaneous left anterior descending artery dissection. AB - Spontaneous coronary artery dissection is an unusual condition that mainly happens in fit and healthy women in the peripartum period. Strenuous exercise is a rare cause of dissection in angiographically normal coronary arteries. There is no definitive consensus on the etiology, prognosis and treatment of SCAD. We report a case of successful treatment of a late presentation of a coronary artery dissection secondary to intense physical activity in a 48 year old cyclist who continued to cycle for 3 months post event. PMID- 22045091 TI - Successful percutaneous treatment of suspected embolic left main thrombosis in a patient with a mechanical aortic valve. AB - Left main coronary artery thrombosis is a rare but potentially fatal phenomenon. We present the unusual case of total occlusion of the left main coronary artery suspected to be secondary to embolized thrombus from a patient's mechanical, prosthetic aortic valve resulting in an anterior wall ST elevation myocardial infarction and cardiogenic shock. The acute interventional management and review of literature of left main thrombosis is described. PMID- 22045092 TI - Complex regional pain syndrome following transfemoral catheterization. AB - Complex regional pain syndrome (CRPS) (previously reflex sympathetic dystrophy) is a chronic pain condition usually resulting as a consequence of trauma or surgery. Though described occasionally after vascular surgery, it is distinctly rare after percutaneous cardiovascular procedures. We report a case of CRPS following trans- femoral catheterization-related groin pseudoaneurysm. To our knowledge, this is the first such report following transfemoral catheterization. A 36-year-old female underwent an electrophysiological study and AV node re-entry tachycardia ablation using the left femoral vein approach. One month later she presented complaining of numbness and tingling in her left foot with swelling and mild groin discomfort. A lower extremity duplex scan showed a left common femoral artery pseudoaneurysm that was partially thrombosed and subsequently resolved spontaneously. The patient had intractable symptoms of pain, temperature changes, color changes, and trophic changes of the left foot. Conventional angiography was done to rule out occlusive arterial disease but just showed very sluggish flow. Further evaluation with transcutaneous oxymetry and 3-phase bone scan was consistent with microvascular dysfunction and poor cutaneous blood flow suggestive of cold-type CRPS. In this case report, we also review the clinical features and the vascular changes associated with CRPS and discuss the pathophysiology of the syndrome from a cardiovascular specialist's perspective. Interventionalists should be aware that CRPS is a possible, albeit rare, condition that may follow many vascular procedures that they perform on a daily basis. PMID- 22045093 TI - Beyond the bend: a literature review and case report of radial artery loop. AB - Transradial cardiac catheterization is an exciting technique that has many advantages over the traditional femoral approach. Most importantly it is a safe option for PCI with potential same day discharge for uncomplicated cases. Despite its advantages, some challenges may be encountered with the transradial approach. After arterial access and spasm, vascular artery anomalies constitute a significant number of procedural failure. Radial artery anomalies are encountered in greater than 17% of cases performed in literature. In particular, radial loop is an important cause of transradial procedural failure. We present a literature review and a case from our institution and outline techniques in order to traverse the loop and make the transradial approach a success. PMID- 22045095 TI - Economic analysis of the implementation of guidelines for type 2 diabetes control developed by Diabetes Poland: what increase in costs is justified by clinical results? AB - INTRODUCTION: Diabetes Poland has recently published guidelines for the treatment of type 2 diabetes. Treatment according to these guidelines is more expensive and requires more involvement of the patient than is the case in current clinical practice. OBJECTIVES: The aim of the study was to assess to what extent the cost of type 2 diabetes treatment according to the Diabetes Poland guidelines may be increased when compared with the cost of the current treatment, so that the introduction of the guidelines remains cost-effective in the Polish setting. PATIENTS AND METHODS: Two hypothetical patients were defined, John and Peter, representing the population of newly diagnosed type 2 diabetic patients. The disease progression was simulated assuming that John is treated according to the current practice and Peter is treated to achieve and maintain the goals defined by Diabetes Poland. The simulation was performed using the CORE model, which has been constructed based on the published scientific evidence and includes more than a dozen of diabetes complications. The model has been widely validated by numerous studies and is broadly used; it enables a reliable estimation of costs and clinical effects associated with diabetes. The parameters of the model were adapted to the Polish conditions. The analysis was conducted in a life-long perspective, discounting of costs/effects was included, and the acceptability threshold was set at 25,511 EUR per quality-adjusted life-year (QALY). RESULTS: The quality-adjusted life expectancy of John will be 0.3 QALY lower than the life expectancy of Peter. The treatment of diabetic complications will be 400 EUR more expensive in the case of John compared with that of Peter. Assuming the willingness to pay at the level of 7500 EUR/QALY, the cost of diabetes treatment of Peter may be 250 EUR higher than that of John's treatment. For the threshold level of 15,000 EUR/QALY, the difference in cost may be 450 EUR, and for the threshold level of 25,000 EUR/QALY - 725 EUR per year. CONCLUSIONS: Treatment according to the guidelines of Diabetes Poland may be cost-effective provided that the additional costs associated with intensification of therapy will not exceed 725 EUR per year. PMID- 22045094 TI - Efficacy and safety comparison of continuous glucose monitoring and self monitoring of blood glucose in type 1 diabetes: systematic review and meta analysis. AB - INTRODUCTION: Self-monitoring of blood glucose (SMBG) is a crucial element of clinical care in type 1 diabetes, but it may not provide adequate glucose control. A newer alternative approach is continuous glucose monitoring (CGM) system, which allows a more thorough metabolic control. However, the results of trials comparing CGM with SMBG are inconsistent. OBJECTIVES: Based on a systematic review and meta-analysis, we aimed to assess the efficacy and safety of various CGM systems compared with SMBG. METHODS: We searched major medical databases up to June 2011 for randomized controlled trials comparing CGM and SMBG in type 1 diabetes. Studies of at least 12-week duration were included. Weighted mean difference (WMD) or standardized mean difference (SMD) was calculated for continuous measures and dichotomous data were expressed as odds ratio (OR) or risk ratio. RESULTS: We identified 14 relevant trials including a total of 1268 type 1 diabetic patients, of whom 670 were randomized to the CGM group and 598 to the SMBG group. Patients using CGM had a greater decrease in hemoglobin A1c (HbA1c) from baseline compared with those using SMBG (WMD -0.26% [-0.34; -0.19]). We found that the magnitude of the effect was similar in the subset of children and adolescents (WMD -0.25% [-0.43; -0.08]) to that in adults (WMD -0.33% [-0.46; -0.2]). Only real-time devices for CGM improved glycemic control (WMD -0.27% [ 0.34; -0.19]). The percentage of patients achieving target HbA1c was higher in the CGM group (OR 2.14 [1.41; 3.26]). Pooled results from 4 studies revealed a reduction in hypoglycemic events in the CGM group (SMD -0.32 [-0.52; -0.13]). CONCLUSIONS: CGM, partcicularly its real-time system, has a favorable effect on glycemic control and decreases the incidence of hypoglycemic episodes in both adult and pediatric patients with type 1 diabetes. PMID- 22045096 TI - Synergy between pharmacological and mechanical reperfusion in ST-segment elevation myocardial infarction patients: 2011 update. PMID- 22045097 TI - Lessons learned from advanced intracoronary imaging in patients with acute myocardial infarction. AB - The use of percutaneous coronary intervention (PCI) as a primary treatment for acute myocardial infarction (AMI) has contributed to save lives. But, in addition to this, it has generated new opportunities to study the culprit and non-culprit arteries with intracoronary imaging during and after reperfusion treatments, and thus to get a richer view of this syndrome. From this perspective, intracoronary imaging has contributed to our knowledge of AMI in a number of ways: it has complemented the available information on the substrate of AMI with in-vivo observations, reinforcing the current pathophysiological paradigm on this entity; it has allowed longitudinal documentation on the reparative vascular processes at the culprit lesion over the months and years following the acute event; it has generated valuable observations on the vascular responses to interventions performed during primary PCI, such as implantation of drug eluting stents (DES); it has been used to guide or monitor specific interventions, either pharmacological agents like antithrombotics or devices like thrombectomy catheters or stents, at the culprit stenosis of AMI; and it has revealed the characteristics of concomitant atheromatosis in non-culprit vessels. In this article, we review the available literature on these different aspects. PMID- 22045098 TI - A study of the clinical and biochemical profile of peritoneal dialysis fluid low in glucose degradation products. AB - OBJECTIVE: Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity. METHODS: We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events. RESULTS: Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor alpha, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years. CONCLUSIONS: It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum. PMID- 22045099 TI - Chronic peritoneal dialysis in children with special needs or social disadvantage or both: contraindications are not always contraindications. AB - OBJECTIVE: Our aim in the present study was to identify outcomes in children with special needs or social disadvantage, or both, receiving chronic peritoneal dialysis (CPD) treatment in a pediatric dialysis unit. METHODS: Among 110 children started on CPD in our unit during the period between November 1995 and November 2008, we identified 13 patients (8 girls, 5 boys) with major physical, mental, or psychosocial problems. Age at CPD initiation in the group with disability ranged from 4.0 years to 16.5 years (median: 7.5 years). Under lying diseases were vesicoureteral reflux (4 patients), neuropathic bladder and vesicoureteral reflux (3 patients), chronic pyelonephritis (3 patients), amyloidosis (2 patients), and Alport syndrome (1 patient). Challenges encountered were adverse family or social circumstances (4 patients), cerebral palsy (3 patients), Down syndrome (1 patient), rectovesical fistula in conjunction with ectopic anus and previous multiple abdominal surgery (1 patient), blindness and deafness (1 patient), ventriculoperitoneal shunt (1 patient), colostomy and malnutrition (1 patient), and mental retardation and blindness (1 patient). All catheters were implanted percutaneously. RESULTS: Median duration of dialysis was 18 months (range: 6 - 124 months). The frequency of peritonitis was not different between children with and without disability (p > 0.05). In children with disability compared with children without disability, the frequencies of catheter related infections (1 episode/79.3 patient-months vs 1 episode/32.4 patient months) and of catheter-related non-infectious complications (1 episode/238 patient-months vs 1 episode/115.7 patient-months) were lower (p < 0.05). Chronic peritoneal dialysis was terminated in 5 children (for renal transplantation in 3, switch to hemodialysis in 1, death in 1). CONCLUSIONS: Our results suggest that, with appropriate family support and an experienced multidisciplinary team, CPD can be effectively performed in children with special needs or social disadvantage, or both. PMID- 22045100 TI - A peritoneal dialysis regimen low in glucose and glucose degradation products results in increased cancer antigen 125 and peritoneal activation. AB - BACKGROUND: Glucose and glucose degradation products (GDPs) in peritoneal dialysis fluids (PDFs) are both thought to mediate progressive peritoneal worsening. METHODS: In a multicenter, prospective, randomized crossover study, incident continuous ambulatory peritoneal dialysis patients were treated either with conventional lactate-buffered PDF (sPD regimen) or with a regimen low in glucose and GDPs: Nutrineal*1, Extraneal*1, and Physioneal*2 (NEPP regimen; all solutions: Baxter Healthcare, Utrecht, The Netherlands). After 6 months, patients were switched to the alternative regimen for another 6 months. After 6 weeks of run-in, before the switch, and at the end of the study, 4-hour peritoneal equilibration tests were performed, and overnight effluents were analyzed for cells and biomarkers. Differences between the regimens were assessed by multivariate analysis corrected for time and regimen sequence. RESULTS: The 45 patients who completed the study were equally distributed over both groups. During NEPP treatment, D(4)/D(0) glucose was lower (p < 0.01) and D/P creatinine was higher (p = 0.04). In NEPP overnight effluent, mesothelial cells (p < 0.0001), cancer antigen 125 (p < 0.0001), hyaluronan (p < 0.0001), leukocytes (p < 0.001), interleukins 6 (p = 0.001) and 8 (p = 0.0001), and vascular endothelial growth factor (VEGF, p < 0.0001) were increased by a factor of 2-3 compared with levels in sPD effluent. The NEPP regimen was associated with higher transport parameters, but that association disappeared after the addition of VEGF to the model. The association between NEPP and higher effluent levels of VEGF could not be attributed to glucose and GDP loads. CONCLUSIONS: Study results indicate preservation of the mesothelium and increased peritoneal activation during NEPP treatment. Whether the increase in VEGF reflects an increase in mesothelial cell mass or whether it points to another, undesirable mechanism cannot be determined from the present study. Longitudinal studies are needed to finally evaluate the usefulness of the NEPP regimen for further clinical use. PMID- 22045101 TI - Hemoglobin variability with epoetin beta and continuous erythropoietin receptor activator in patients on peritoneal dialysis. AB - BACKGROUND AND OBJECTIVES: The extent to which hemoglobin (Hb) cycling occurs in peritoneal dialysis (PD) patients is unclear. It is also uncertain whether different types of erythropoiesis-stimulating agents (ESAs) affect such cycling. We performed a retrospective cohort study of our PD population before and after the entire program was switched from epoetin beta (NeoRecormon: Hoffman-LaRoche, Basel, Switzerland) to continuous erythropoietin receptor activator [CERA (Mircera: Hoffman-LaRoche)]. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The study included 79 patients receiving PD for end-stage renal failure and being treated with an ESA. Hemoglobin concentrations were measured monthly, and each study period ran for 12 months. Patient demographics and details of intercurrent illness and hospital admission were collected. RESULTS: There was a trend to fewer patients on CERA (26 patients, 68.4%) than on epoetin beta (36 patients, 87.8%, p = 0.054) experiencing Hb excursions. The CERA group also required fewer dose changes. However, there was no difference in the proportion of patients experiencing complete Hb cycles. On logistic regression, the factors associated with Hb cycling were ESA dose increase or decrease and hospital admission. We also observed a positive correlation between the delta ESA dose and the amplitude of Hb excursion, suggesting that the dose changes were causal, rather than reactive. CONCLUSIONS: Hemoglobin cycling occurs in PD patients and is largely a consequence of current practice in ESA dosing, plus the effects of intercurrent illness. The longer half life of CERA may offer a small advantage in reducing the degree of Hb variability, possibly because of fewer dose changes per patient. PMID- 22045102 TI - Intraperitoneal vancomycin concentrations during peritoneal dialysis-associated peritonitis: correlation with serum levels. AB - BACKGROUND: For the treatment of peritoneal dialysis-associated peritonitis (PDP), it has been suggested that serum concentrations of vancomycin be kept above 12 mg/L-15 mg/L. However, studies correlating vancomycin concentrations in serum and peritoneal dialysate effluent (PDE) during active infection are sparse. We undertook the present study to investigate this issue and to determine whether achieving the recommended serum level of vancomycin results in therapeutic levels intraperitoneally. METHODS: We studied patients treated with intraperitoneal (i.p.) vancomycin for non-gram-negative PDP. We gave a single dose (approximately 30 mg/kg) at presentation, and we subsequently measured vancomycin levels in PDE on day 5; we wanted to determine if efflux of vancomycin from serum to PDE during a 4-hour dwell was consistent and resulted in therapeutic levels. RESULTS: Of the 48 episodes of PDP studied, serum vancomycin concentrations exceeding 12 mg/L were achieved in 98% of patients, but in 11 patients (23%), a PDE vancomycin level below 4 mg/L--the minimal inhibitory concentration (MIC) of many gram positive organisms--was observed at the end of a 4-hour dwell on day 5. The correlation between the concentrations of vancomycin in serum and PDE (from efflux of antibiotic over 4 hours) was statistically significant, but poor (R(2) = 0.18). CONCLUSIONS: Our data support the International Society for Peritoneal Dialysis statement that adequate serum vancomycin concentrations can be achieved with intermittent dosing (single dose every 5 days), but cannot guarantee therapeutic PDE levels in the treatment of PDP. Intermittent dosing of vancomycin may not consistently result in PDE concentrations markedly greater than MIC of many important pathogens. Although the clinical significance of this finding remains to be determined, it may be preferable to give smaller but more frequent doses of PDE vancomycin (continuous dosing) for adults with PDP (as is currently recommended for children). PMID- 22045103 TI - Modelling the emergence of hallucinations: early acquired vulnerabilities, proximal life stressors and maladaptive psychological processes. AB - BACKGROUND: The study aimed to expand upon existing findings on the vulnerability to psychosis by examining synergistic models of hallucination emergence. Hypothesised vulnerability factors were separated into three stages of vulnerability; early acquired and enduring vulnerabilities (heredity, childhood trauma, early cannabis use), proximal life stressors (life hassles) and psychological appraisals/coping (metacognitions/experiential avoidance). METHODS: Participants were recruited to a non-clinical sample (N = 133) and a clinical sample of psychosis patients (N = 100). RESULTS: Path analyses in the non clinical sample indicated that experiences of childhood emotional trauma, in combination with subsequent experiences of life hassles, best predicted vulnerability to both hallucinations in general and auditory hallucinations specifically. This pathway was partially mediated by negative metacognitions. The models were then replicated in the clinical sample, with two notable differences: (1) childhood sexual trauma replaced childhood emotional trauma as the best enduring predictor in the clinical model. (2) Experiential avoidance replaced metacognitions as the best cognitive predictor of hallucinations. CONCLUSIONS: The study's findings highlighted how vulnerability to hallucinations can occur developmentally across time, with early acquired vulnerability factors, combining additively with more proximal day-to-day factors and cognitive style, to propel a person further towards the formation of hallucinations. PMID- 22045104 TI - Sunitinib-induced asthenia: from molecular basis to clinical relief. AB - Asthenia-fatigue syndrome (AFS) is defined as a persistent, subjective sense of tiredness related to cancer or its treatment and greatly impacts quality of life among cancer patients. All tyrosine kinase inhibitors, but especially sunitinib, may induce AFS. The reason for sunitinib-induced AFS is not yet well understood. Adverse events caused by sunitinib associated with AFS may include anemia, hypothyroidism, nausea and vomiting. However, AFS is also reported when active treatment with sunitinib is ongoing, and no other relevant adverse event can justify it. The molecular mechanisms by which sunitinib triggers AFS remain elusive. Sunitinib displays multiple off-target tyrosine-kinase interactions and competitively inhibits multiple proteins through the blockade of their ATP binding sites. The broad spectrum of kinases inhibited may play a key role not only in terms of activity but also in terms of toxicity induced by sunitinib. This study considered different clinical observations and current metabolic and pharmacological knowledge, leading to hypotheses regarding which molecular mechanisms may be involved in sunitinib-induced AFS in cancer patients. Deeper knowledge of the molecular mode of action of sunitinib may lead to improved optimization of its clinical use. PMID- 22045105 TI - Vitamin D and falls--are intermittent, high doses better? PMID- 22045106 TI - Pediatric SDHB pheochromocytoma: a link to metastasis. PMID- 22045107 TI - DES--adverse health outcomes after in utero exposure. PMID- 22045108 TI - Efficacy of behavioral interventions in patients with poorly controlled diabetes mellitus. PMID- 22045109 TI - Bone: low-dose glucocorticoid replacement does not reduce BMD. PMID- 22045110 TI - Ratiometric fluorescence detection of cyanide based on a hybrid coumarin hemicyanine dye: the large emission shift and the high selectivity. AB - A new ratiometric fluorescent cyanide probe was developed based on the nucleophilic attack of CN(-) toward the indolium group of a hybrid coumarin hemicyanine dye, by which high selectivity as well as large emission shift could be achieved. PMID- 22045111 TI - Massive bilateral renal angiomyolipomatosis and multifocal micronodular pneumocytes hyperplasia associated with tuberous sclerosis: a case report. AB - Tuberous sclerosis (TS) is an autosomal-dominant disorder characterized by a variety of hamartomatous lesions in various organs. Various organ involvements can be detected with radiology: neurologic involvement (cortical tubers, subependymal nodules and white matter abnormalities), renal involvement (angiomyolipoma) and pulmonary involvement (pulmonary lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia). Here, we are reporting a case of tuberous sclerosis with multiple organ involvement and massive bilateral AMLs in a 49-year-old female patient. PMID- 22045112 TI - Use of OROS(r) hydromorphone in the treatment of osteoarthritis and osteoporosis: A pooled analysis of three non-interventional studies focusing on different starting doses. AB - OBJECTIVE: To determine the effect of a lower starting dose of OROS(r) hydromorphone compared with a higher starting dose. DESIGN: Data from the first 15 days of treatment were compared in a combined analysis of three prospective, non-interventional studies. SETTING: Non-interventional, carried out in daily routine settings. PATIENTS: Patients had chronic severe pain due to osteoarthritis or from fragility fractures related to osteoporosis. INTERVENTIONS: OROS-ANA-4001 and OROS-ANA-4002 had a daily starting dose of 8 mg of OROS(r) hydromorphone; OROS-ANA-4003 had a daily starting dose of 4 mg. MAIN OUTCOME MEASURE(S): A post-hoc analysis to assess the effect of a low starting dose of OROS(r) hydromorphone on tolerability, pain control, and treatment satisfaction overall and for subgroups of opioid-naive patients versus patients previously treated with opioids, and patients aged >65 years versus patients aged <=65 years. RESULTS: Treatment satisfaction and pain control improved in all studies; treatment satisfaction improved in a higher percentage of patients in the lower starting dose group. Gastrointestinal disorders were the most frequent treatment-emergent adverse events. Incidence of nausea was comparable between studies. Incidence of constipation, vomiting, fatigue, and pruritus was less frequent with the lower starting dose. In elderly and opioid-naive patients, a lower starting dose was associated with lower overall incidence of adverse events, treatment-related adverse events, and those leading to discontinuation. CONCLUSIONS: A lower starting dose was associated with better tolerability and a lower number of treatment terminations at a comparable level of pain control with high treatment satisfaction. PMID- 22045114 TI - Seasonal and diel dive performance and behavioral ecology of the bimodally respiring freshwater turtle Myuchelys bellii of eastern Australia. AB - Freshwater turtles have an extraordinary physiological ability to endure dive times that can range from days to months using aquatic respiration. In cryptodires (e.g., white-lipped mud turtle Kinosternon leucostomum) aquatic respiration is via buccal or cutaneous routes whereas in pleurodires (e.g., Fitzroy River turtle Rheodytes leukops), it is achieved primarily via specialized cloacal bursae. This study records the voluntary diving performance of the western sawshelled turtle Myuchelys bellii in Bald Rock Creek from the temperate zone of the Murray-Darling Basin of Australia. Myuchelys bellii has a moderately specialized cloacal bursae morphology compared to other pleurodiran turtles and displays impressive dive durations spanning more than 15 days during the winter months. This is attributed to its ability to maintain aerobic dives via its cloacal bursae and low water temperatures in winter. Myuchelys bellii seasonal and diel diving performance, including its crepuscular habit, is comparable to R. leukops and Elseya albagula. This study also recorded the first aquatic hibernation at depth (>3 m) for any freshwater turtle; and only the second pleurodire to demonstrate aquatic hibernation as an overwintering strategy. Observed thermoregulation behavior in M. bellii is believed to provide multiple life history benefits. PMID- 22045113 TI - Electroencephalogram bands modulated by vigilance states in an anuran species: a factor analytic approach. AB - Dramatic changes in neocortical electroencephalogram (EEG) rhythms are associated with the sleep-waking cycle in mammals. Although amphibians are thought to lack a neocortical homologue, changes in rest-activity states occur in these species. In the present study, EEG signals were recorded from the surface of the cerebral hemispheres and midbrain on both sides of the brain in an anuran species, Babina daunchina, using electrodes contacting the meninges in order to measure changes in mean EEG power across behavioral states. Functionally relevant frequency bands were identified using factor analysis. The results indicate that: (1) EEG power was concentrated in four frequency bands during the awake or active state and in three frequency bands during rest; (2) EEG bands in frogs differed substantially from humans, especially in the fast frequency band; (3) bursts similar to mammalian sleep spindles, which occur in non-rapid eye movement mammalian sleep, were observed when frogs were at rest suggesting sleep spindle-like EEG activity appeared prior to the evolution of mammals. PMID- 22045115 TI - Aluminium, iron and copper in human brain tissues donated to the Medical Research Council's Cognitive Function and Ageing Study. AB - Aluminium, iron and copper are all implicated in the aetiology of neurodegenerative diseases including Alzheimer's disease. However, there are very few large cohort studies of the content of these metals in aged human brains. We have used microwave digestion and TH GFAAS to measure aluminium, iron and copper in the temporal, frontal, occipital and parietal lobes of 60 brains donated to the Cognitive Function and Ageing Study. Every precaution was taken to reduce contamination of samples and acid digests to a minimum. Actual contamination was estimated by preparing a large number of (170+) method blanks which were interspersed within the full set of 700+ tissue digests. Subtraction of method blank values (MBV) from tissue digest values resulted in metal contents in all tissues in the range, MBV to 33 MUg g(-1) dry wt. for aluminium, 112 to 8305 MUg g(-1) dry wt. for iron and MBV to 384 MUg g(-1) dry wt. for copper. While the median aluminium content for all tissues was 1.02 MUg g(-1) dry wt. it was informative that 41 brains out of 60 included at least one tissue with an aluminium content which could be considered as potentially pathological (> 3.50 MUg g(-1) dry wt.). The median content for iron was 286.16 MUg g(-1) dry wt. and overall tissue iron contents were generally high which possibly reflected increased brain iron in ageing and in neurodegenerative disease. The median content for copper was 17.41 MUg g(-1) dry wt. and overall tissue copper contents were lower than expected for aged brains but they were commensurate with aged brains showing signs of neurodegenerative disease. In this study we have shown, in particular, the value of carrying out significant numbers of method blanks to identify unknown sources of contamination. When these values are subtracted from tissue digest values the absolute metal contents could be considered as conservative and yet they may still reflect aspects of ageing and neurodegenerative disease in individual brains. PMID- 22045116 TI - Photoinactivation of cell-free human immunodeficiency virus by hematoporphyrin monomethyl ether. AB - Human immunodeficiency virus (HIV) particles that remain in the blood of patients are frequently ignored as targets for AIDS treatment. We therefore investigated the use of photodynamic therapy (PDT) with hematoporphyrin monomethyl ether (HMME) as a means of inactivating cell-free HIV in vitro. Virus particles including HIV-1(IIIB), resistant HIV-1 variants, HIV-1 clinical variants, and HIV 2 variants were incubated with HMME for 40 min, followed by irradiation with a 630-nm semiconductor laser at an energy density of 0.3 J/cm(2). The antiviral effects were evaluated by counting syncytium formation or measuring p24 antigen expression levels in supernatants by enzyme-linked immunosorbent assay. The relationships between photoinactivation and HMME concentrations, energy density, power density and antioxidants (NaN(3) and D: -mannitol) were also assessed using the above methods. All the tested virus particles were completely responsive to HMME-PDT. HMME concentration and energy density were positively correlated with photoinactivation of HIV, while power density was negatively correlated. Both sodium azide and D: -mannitol weakened the inhibitory effect of PDT on virus induced membrane fusion, with D: -mannitol having a stronger effect. HMME-PDT can inactivate HIV particles, and may therefore represent a promising treatment for AIDS patients. PMID- 22045117 TI - Reactions of nurses to the use of electronic health record alert features in an inpatient setting. AB - While studies have been conducted to assess nurse perception of electronic health records, once electronic health record systems are up and running, there is little to guide the use of features within the electronic health record for nursing practice. Alerts are a promising tool for implementing best practice for patient care in inpatient settings. Yet the use of alerts for inpatient nursing is understudied. This study examined nurse attitudes and reactions to alerts in the inpatient setting. Focus groups were conducted at three hospitals with 50 nurses. Nurses were asked about five different alert features. For each alert, participants were asked about their feelings and reactions to the alert, how alerts help or hinder work, and suggestions for improvements. Findings include clear preferences for alert types and content. Nurses preferred a dashboard style alert with functions included to accomplish tasks directly in the alert. While nurses reported positive reactions to certain alert pages, they also reported low use of those features and occasional distrust of the data included in alerts. Findings provide guidance for future use of alerts and design of new alerts. Findings also identify the important challenge of designing and implementing alerts for integration with nursing workflow. PMID- 22045118 TI - Glioblastoma survival in the United States before and during the temozolomide era. AB - The standard-of-care treatment for newly diagnosed glioblastoma changed in 2005, when radiation therapy plus temozolomide chemotherapy replaced radiation therapy alone. It is not yet clear how this change in treatment has influenced patient survival in routine clinical practice, or if a survival benefit extends to patients older than those enrolled in the trial. Data from the Surveillance, Epidemiology, and End Results (SEER) Program was analyzed to compare survival of adult glioblastoma patients diagnosed from 2000-2003 to patients diagnosed from 2005-2008, in order to evaluate pre-temozolomide and post-temozolomide periods. The Kaplan-Meier method and Cox proportional hazards models were used. 6,673 patients with glioblastoma diagnosed from 2000-2003 and 7,259 patients diagnosed from 2005-2008 were identified. Median survival times of all patients diagnosed in the 2000-2003 and 2005-2008 periods were 8.1 and 9.7 months, respectively. Amongst patients treated with surgery and a radiation-containing regimen, median survival was 12.0 months in 2000-2003 and 14.2 months in 2005-2008. In the temozolomide era, median survival times ranged from a high of 31.9 months in patients age 20-29 to a low of 5.6 months in patients age 80 and older. The survival of patients with newly diagnosed glioblastoma improved from 2000-2003 to 2005-2008, likely due to temozolomide use. However, median survival time after glioblastoma diagnosis in the SEER population remains well under one year, largely driven by poor prognosis in elderly patients. PMID- 22045119 TI - A systematic study on the synthesis, reactivity and structure of ortho-palladated aryloximes, including the first cyclopalladated aryloximato and iminoaryloxime complexes. AB - Complexes [Pd{C,N-Ar{C(Me)=NOH}-2}(MU-Cl)](2) (1) with Ar = C(6)H(4), C(6)H(3)NO(2)-5 or C(6)H(OMe)(3)-4,5,6, were obtained from the appropriate oxime, Li(2)[PdCl(4)] and NaOAc. They reacted with neutral monodentate C-, P- or N-donor ligands (L), with [PPN]Cl ([PPN] = Ph(3)P=N=PPh(3)), with Tl(acac) (acacH = acetylacetone), or with neutral bidentate ligands N^N (tetramethylethylenediamine (tmeda), 4,4'-di-tert-butyl-2,2'-bipyridine ((t)Bubpy)) in the presence of AgOTf or AgClO(4) to afford complexes of the types [Pd{C,N-Ar{C(Me)=NOH}-2}Cl(L)] (2), [PPN][Pd{C,N-Ar{C(Me)=NOH}-2}Cl(2)] (3), [Pd{C,N-Ar{C(Me)=NOH}-2}(acac)] (4) or [Pd{C,N-Ar{C(Me)=NOH}-2}(N^N)]X (X = OTf, ClO(4)) (5), respectively. Complexes 1 reacted with bidentate N^N ligands in the presence of a base to afford mononuclear zwitterionic oximato complexes [Pd{C,N-Ar{C(Me)=NO}-2}(N^N)] (6). Dehydrochlorination of complexes 2 by a base yielded dimeric oximato complexes of the type [Pd{MU-C,N,O-Ar{C(Me)[double bond, length as m-dash]NO}-2}L](2) (7). The insertion of XyNC into the Pd-C(aryl) bond of complex 2 produced the mononuclear iminoaryloxime derivative [Pd{C,N-C(=NXy)Ar{C(Me)=NOH}-2}Cl(CNXy)] (8) which, in turn, reacted with [AuCl(SMe(2))] to give [Pd{MU-N,C,N-C(=NXy)Ar{C(Me)=NOH} 2}Cl](2) (9) with loss of XyNC. Some of these complexes are, for any metal, the first containing cyclometalated aryloximato (6, 7) or iminoaryloxime (8, 9) ligands. Various crystal structures of complexes of the types 2, 3, 6, 7, 8 and 9 have been determined. PMID- 22045120 TI - The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis. AB - OBJECTIVES: Irritable bowel syndrome (IBS) affects 10-15% of the population, and treatment options are limited. Rifaximin is a minimally absorbed antibiotic that has shown efficacy in IBS patients. The objective of our study was to perform a meta-analysis and systematic review of available randomized, placebo controlled trials evaluating the efficacy and tolerability of rifaximin in patients with IBS. METHODS: We performed a systematic literature search of multiple online electronic databases regardless of language. Inclusion criteria entailed randomized, placebo controlled trials and IBS defined by accepted symptom-based criteria. Meta-analysis was conducted to evaluate the summary odds ratios (ORs) and 95% confidence intervals (CIs) of combined studies for the primary and secondary outcomes using a random-effects model based on the DerSimonian and Laird method to reflect both within- and between study variability. We assessed heterogeneity using chi(2) test and the inconsistency index statistic (I(2)). Significant heterogeneity was defined as I(2) >=25%. Meta-regression was performed using generalized linear mixed-effects model and study as random effects to estimate the summary OR adjusting for covariate differences across studies and treatment group. Publication bias was assessed by funnel plot analysis. RESULTS: Systematic review identified 13,700 citations. Eighteen were deemed to be potentially relevant, of which five articles met eligibility. Meta analysis found rifaximin to be more efficacious than placebo for global IBS symptom improvement (OR=1.57; 95% CI=1.22, 2.01; therapeutic gain=9.8%; number needed to treat (NNT)=10.2), with mild heterogeneity (P=0.25, I(2)=26%). For the key secondary outcome of bloating, raw data were available for four studies. Rifaximin was significantly more likely to improve bloating than placebo (OR=1.55; 95% CI=1.23-1.96; therapeutic gain=9.9%; NNT=10.1), with no significant heterogeneity (P=0.27, I(2)=23%). We found that studies with older patients and more females demonstrated higher response rates, which was consistent regardless of treatment group. In addition, studies with higher cumulative dose tended to report a higher response rate. Of the covariates evaluated, we found age to be most predictive of response, with a correlation coefficient of 0.97 between aggregate response rate and mean age in the placebo groups. Although studies with higher cumulative dose tended to show increased response rates, this was also seen consistently in both the treated and placebo groups. Adverse effects were similar among patients receiving rifaximin or placebo in all studies. The most common adverse events (AEs) (<=10%) with rifaximin were headache, upper respiratory infection, nausea, nasopharygitis, diarrhea, and abdominal pain. Serious AEs were rare (<1%) and similar with rifaximin and placebo. CONCLUSIONS: Rifaximin proved more effective than placebo for global symptoms and bloating in IBS patients. The modest therapeutic gain was similar to that yielded by other currently available therapies for IBS. AEs were similar between rifaximin and placebo. PMID- 22045121 TI - Hybrid functional electronic structure of PbPdO2, a small-gap semiconductor. AB - PbPdO2, a ternary compound containing the lone pair active ion Pb2+ and the square planar d8Pd2+ ion, has attracted recent interest because of the suggestion that its electronic structure, calculated within density functional theory using either the local density or the generalized gradient approximation, displays zero gap behavior. In light of the potential ease of doping magnetic ions in this structure, it has been suggested that the introduction of spin, in conjunction with zero band gap, can result in unusual magnetic ground states and unusual magnetotransport. It is known that most electronic structure calculations do not properly obtain a band gap even for the simple oxide PdO, and instead obtain a metal or a zero-gap semiconductor. Here we present density functional calculations employing a screened hybrid functional which correctly obtain a band gap for the electronic structure of PdO. When employed to calculate the electronic ground state of PbPdO2, a band gap is again obtained, which is consistent with both the experimental data on this compound, as well as a consideration of valence states and of metal-oxygen connectivity in the crystal structure. We also present comparisons of the absolute positions (relative to the vacuum level) of the conduction band minima and the valence band maxima in alpha PbO, PdO and PbPdO2, which suggest ease of p-type doping in PbPdO2, that has been observed even in nominally pure materials. PMID- 22045122 TI - Matrix metalloproteinase 2 induces epithelial-mesenchymal transition in proximal tubules from the luminal side and progresses fibrosis in mineralocorticoid/salt induced hypertensive rats. AB - OBJECTIVES: Excess mineralocorticoids such as deoxycorticosterone acetate (DOCA) together with salt are known to cause tubulointerstitial fibrosis, but the mechanisms underlying fibrosis progression are unclear. Therefore, we investigated the role of matrix metalloproteinase 2 (MMP2) in the epithelial mesenchymal transition and fibrosis progression. METHODS: Uninephrectomized rats drank 0.9% NaCl and 0.3% KCl solution and were treated with DOCA alone, DOCA + spironolactone, or vehicle for 1, 4, or 8 weeks. SBP, kidney function and morphology, and kidney and urine MMP2 activity were compared among the groups. RESULTS: At week 4, the DOCA-treated group exhibited hypertension, tubulointerstitial fibrosis, increased MMP2 activity in the kidney and urine, and overexpression of MMP2 in proximal tubule cells and MMP14 in apical membranes; these results were more pronounced at week 8. At week 8, the proximal tubule cell apicolateral surface proteins villin, claudin 2, and E-cadherin were downregulated, and the mesenchymal marker alpha-smooth muscle actin was upregulated in the tubulointerstitium of DOCA-treated rats. These DOCA/salt induced changes (except for hypertension) and fibrosis progression observed at week 8 were reversed by TISAM (a selective MMP2 inhibitor), which was administered from week 4 to week 8. All of the effects of DOCA/salt at week 8 were attenuated by spironolactone. CONCLUSION: Eight weeks of treatment with DOCA/salt activated MMP2, primarily on the apical surface of proximal tubule cells, which induced epithelial-mesenchymal transition from the luminal side and promoted tubulointerstitial fibrosis progression. These MMP2-induced changes occurred via downstream processes regulated by mineralocorticoid receptors. PMID- 22045123 TI - Cardiac benefits of exercise training in aging spontaneously hypertensive rats. AB - OBJECTIVE: To evaluate the effect of low-intensity chronic exercise training (ExT) on blood pressure (BP), as well as the cardiac alterations associated with hypertension in aging hypertensive rats. METHODS: Male spontaneously hypertensive rats (SHR; 21 months old) and their normotensive control Wistar-Kyoto (WKY) rats were submitted to low-intensity training protocol for 13 weeks. BP, cardiac morphological and morphometric analysis, as well as gene expression of fibrotic and inflammatory factors were analyzed at the end of the training period. RESULTS: ExT reduced BP and heart rate in aged SHR. Left ventricle hypertrophy, collagen volume fraction and wall-to-lumen ratio of myocardium arterioles were also decreased in trained SHR. However, ExT was unable to reverse the either reduced capillary density or the cardiac myocyte hypertrophy observed in SHR as compared with WKY rats. Trained SHR showed higher metalloproteinase-2/tissue inhibitor metalloproteinase-2 (MMP-2/TIMP-2) ratio and lower levels of alpha smooth muscle actin, but similar levels of connective tissue growth factor, transforming growth factor beta or IL-1 beta to that of nontrained SHR. CONCLUSION: Low to moderate-intensity chronic ExT reverses the cardiac alterations associated with hypertension: myocardial arteriole, left ventricle hypertrophy, collagen content and tachycardia. These changes could be consequence or cause of the reduction in BP observed in trained SHR. In addition, ExT does not worsen the underlying inflammatory burden associated with hypertension. Therefore, the data support a beneficial effect of ExT in aging SHR similar to that reported in young or middle-aged individuals, confirming that exercise is a healthy habit that induces cardiac improvements independently of age. PMID- 22045124 TI - Salt-inducible kinase 1 influences Na(+),K(+)-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure. AB - OBJECTIVES: Essential hypertension is a complex condition whose cause involves the interaction of multiple genetic and environmental factors such as salt intake. Salt-inducible kinase 1 (SIK1) is a sucrose-nonfermenting-like kinase isoform that belongs to the AMPK (5' adenosine monophosphate-activated protein kinase) family. SIK1 activity is increased by high salt intake and plays an essential role in regulating the plasma membrane Na(+),K(+)-ATPase. The objective of this study was to examine whether SIK1 is present in vascular smooth muscle cells (VSMCs) and endothelial cells, whether it affects VSMC Na(+),K(+)-ATPase activity and whether human SIK1 (hSIK1) represents a potential candidate for blood pressure regulation. METHODS: Localization of SIK1 was performed using immunohistochemistry, mRNA and western blot. Functional assays (Na(+),K(+)-ATPase activity) were performed in VSMCs derived from rat aorta. Genotype-phenotype association studies were performed in three Swedish and one Japanese population based cohorts. RESULTS: SIK1 was localized in human VSMCs and endothelial cells, as well as a cell line derived from rat aorta. A nonsynonymous single nucleotide polymorphism in the hSIK1 gene exon 3 (C->T, rs3746951) results in the amino acid change (15)Gly->Ser in the SIK1 protein. SIK1-(15)Ser was found to increase plasma membrane Na(+),K(+)-ATPase activity in cultured VSMC line from rat aorta. Genotype-phenotype association studies in three Swedish and one Japanese population-based cohorts suggested that T allele (coding for (15)Ser) was associated with lower blood pressure (P = 0.005 for SBP and P = 0.002 for DBP) and with a decrease in left ventricular mass (P = 0.048). CONCLUSION: The hSIK1 appears to be of potential relevance within VSMC function and blood pressure regulation. PMID- 22045125 TI - Endothelial vasodilatation in newborns is related to body size and maternal hypertension. AB - OBJECTIVE: The fetal response to an adverse intrauterine environment - reflected in low birth weight - is thought to cause an increased risk for adult hypertension. A possible mechanism by which fetal adaptive responses contribute to hypertension is an adverse effect on endothelial function. Identifying individuals with endothelial dysfunction as early as possible may assist in understanding the inverse association between birth weight and hypertension. The present study aimed to identify determinants of endothelial vasodilatation in the first week of life. METHODS: One hundred and four term newborns were studied in the first week after birth with regard to maximum vasodilatation in response to acetylcholine (endothelium-dependent) and nitroprusside (endothelium-independent) in the vasculature of the forearm skin, by use of a laser-Doppler device and iontophoresis. Bivariable and multivariable linear regression with various familial, gestational and neonatal potential covariates were used for the analysis. RESULTS: In the bivariable analysis, maximum perfusion after administration of acetylcholine was positively associated with birth weight, length, head circumference and maternal education level, but negatively associated with maternal hypertension during pregnancy. In the multivariable analysis, head circumference [b = 11.9 perfusion units/z-score, P = 0.02] and hypertension during pregnancy (b = -25.3 perfusion units from nonhypertensive to hypertensive, P = 0.02) remained significantly associated. Maximum perfusion after administration of nitroprusside was not related to any of the anthropometric measures; it was, however, related to gestational age (b = -11.1 perfusion units/week, P = 0.009). CONCLUSION: This study showed that body size, head circumference in particular, is positively associated with endothelial vasodilatation in newborns, whereas hypertension during pregnancy is inversely associated with endothelial vasodilatation. PMID- 22045126 TI - Evaluation of bivalves as bioindicators of metal pollution in freshwater. AB - The fresh water bivalves, Lamellidens corrianus, Lamellidens marginalis, and Indonaia caeruleus were exposed to chronic concentration of arsenic (0.1719 ppm), cadmium (0.1284 ppm), copper (0.033 ppm), lead (1.50 ppm), mercury (0.0443 ppm) and zinc (1.858 ppm) separately up to 30 days in laboratory. Dry weight of each animal was used to calculate metal concentrations (MUg/g) and the metal body burden (MUg/individual). It was observed that lead (1235.4 MUg/g) and arsenic (37.9 MUg/g) concentration were highest in Lamellidens corrianus, zinc (3,032.3 MUg/g) was highest in Lamellidens marginalis, while mercury (5.87 MUg/g), cadmium (142 MUg/g) and copper (826.7 MUg/g) was highest in Indonaia caeruleus. PMID- 22045127 TI - Addition of N-terminal peptide sequences activates the oncogenic and signaling potentials of the catalytic subunit p110alpha of phosphoinositide-3-kinase. AB - Addition of short (6 to 16 amino acids) peptide sequences to the N-terminus of p110alpha induces a gain of function. Such sequences include the common Flag, His, and VSV tags as well as random sequences. An N-terminal myristylation signal generally believed to activate p110alpha by providing a constitutive membrane address is also activating, if myristylation is mutationally abolished. The gain of function seen with N-terminally tagged (NTT) p110alpha constructs extends to signaling, oncogenic transformation and stimulation of cell growth. The activating effect of N-terminal tags requires a functional Ras-binding domain in p110alpha. Mutations in that domain (T208D and K227A) abolish the gains of function in oncogenicity and signaling. The dominant negative mutant of Ras, RasN17, interferes with transformation induced by NTT p110alpha. In contrast, binding to p85 activity is not required for cellular transformation and enhanced signaling by NTT p110alpha. PMID- 22045128 TI - Assessment of neuromuscular block at the orbicularis oris, corrugator supercilii, and adductor pollicis muscles. AB - PURPOSE: We studied neuromuscular block at the orbicularis oris, corrugator supercilii, and adductor pollicis muscles in anesthetized patients. METHODS: Fifty-four adult patients undergoing air-oxygen-sevoflurane-fentanyl and epidural anesthesia were randomly divided into orbicularis oris, corrugator supercilii, and adductor pollicis groups of 18 patients each. In the three groups, the degree of neuromuscular block caused by rocuronium 0.6 mg/kg was monitored at the orbicularis oris, corrugator supercilii, and adductor pollicis muscles acceleromyographically. RESULTS: Onset of neuromuscular block did not significantly differ among the three groups [157 +/- 60, 186 +/- 73, and 148 +/- 45 s; mean +/- standard deviation (SD)]. Minimum value of 1st stimulation in train-of-four (T1)/control at the corrugator supercilii group was significantly higher than in the orbicularis oris and adductor pollicis groups (0.108 +/- 0.066 vs. 0.021 +/- 0.024 and 0.002 +/- 0.007; P < 0.001). T1/control at the orbicularis oris group was significantly higher than at the adductor pollicis group 30 min after rocuronium (P < 0.05). T1/control at the corrugator supercilii group was significantly higher than at the orbicularis oris and adductor pollicis groups 10-30 and 10-40 min, respectively, after rocuronium (P < 0.05). Train-of four ratios at the orbicularis oris and corrugator supercilii groups were significantly higher than at the adductor pollicis group 40-120 min after rocuronium (P < 0.05). CONCLUSION: The corrugator supercilii muscle is more resistant to rocuronium than the orbicularis oris and adductor pollicis muscles. Recovery of neuromuscular block at the orbicularis oris muscle is slower than that at the corrugator supercilii muscle but was faster than that at the adductor pollicis muscle. PMID- 22045129 TI - The essence of nursing. PMID- 22045130 TI - Deviations in endotracheal cuff pressure during intensive care. PMID- 22045132 TI - Endotracheal cuff pressure monitoring: another alarm in the ICU? PMID- 22045134 TI - Technology and caring. PMID- 22045135 TI - Nurses making a difference. PMID- 22045136 TI - New technologies create communications challenges. PMID- 22045138 TI - Consider alcohol as an element in ventilator weaning failure. PMID- 22045140 TI - Caregiving for patients with heart failure: impact on patients' families. AB - BACKGROUND: Factors that affect the impact of caregiving on patients' family members who provide care to patients with heart failure have not been adequately addressed. In addition, social support and positive aspects of caregiving have received little attention. OBJECTIVE: To identify factors associated with the impact of caregiving. METHODS: Self-report data were collected from 76 dyads of patients with heart failure and their family caregivers. Clinical data were obtained from medical records. RESULTS: A sense of less family support for caregiving was associated with a higher New York Heart Association class of heart failure, being a nonspousal caregiver, lower caregivers' perceived control, and less social support. More disruption of caregivers' schedules was associated with higher class of heart failure, more care tasks, and less social support. Greater impact of caregiving on caregivers' health was related to more recent patient hospitalization, lower caregivers' perceived control, and less social support. Nonwhite caregivers and caregivers whose family member had fewer emergency department visits felt more positive about caregiving than did other caregivers. Social support had a moderating effect on the relationship between patients' comorbid conditions and positive aspects of caregiving. CONCLUSIONS: Caregiving has both positive and negative effects on family caregivers of patients with heart failure. The findings suggest the need for interventions to increase caregivers' sense of control and social support. Family caregivers may need additional support immediately after patient hospitalizations to minimize the negative impact of caregiving. PMID- 22045141 TI - Involving users in the development of effective critical care discharge information: a focus group study. AB - BACKGROUND: Discharge from critical care to a general care unit is a difficult period, and more effective information is needed to support patients and their families at this time. OBJECTIVES: This study sought the views of patients, relatives and health care staff on (1) the most effective methods of delivering critical care discharge information, (2) the required information content of any proposed strategies, (3) the benefits and limitations of any existing strategies, and (4) potential resource implications. METHODS: In this qualitative focus group study, 11 adult patients, 8 family members, and 23 health care staff in Eng-land took part in 8 focus group interviews at 2 hospitals. The computer software program NVIVO7 was used for thematic analysis of the data. RESULTS: Three key themes were identified from the data: (1) considerations related to effective discharge information, (2) goals of critical care discharge information, and (3) resource implications. CONCLUSIONS: This focus group study provides unique user insight into what influences successful and unsuccessful information giving. Based on real experiences, it adds to the limited international body of current evidence. Findings will be of value in designing future critical care discharge information and identifying the related resource implications. PMID- 22045142 TI - Use of a noninvasive electromagnetic device to place transpyloric feeding tubes in critically ill children. AB - BACKGROUND: The start of transpyloric feedings is often delayed because of challenges in reliably placing tubes blindly at the bedside. OBJECTIVE: To determine whether tube placement with the guidance of a noninvasive computerized electromagnetic device shortens the time needed to achieve accurate placement of transpyloric feeding tubes in critically ill children. METHODS: In a prospective, randomized trial in a tertiary-care, university-affiliated pediatric intensive care unit, 49 children requiring transpyloric feeding tube placement were randomized to have their tube placed by using conventional blind technique or with the assistance of a noninvasive electromagnetic device. RESULTS: Twenty seven patients were randomized to blind placement, and 22 were randomized to the electromagnetic device group. The time required to place the tubes successfully was significantly longer (P < .03) in the electromagnetic device group (median, 9.5 minutes; 95% confidence interval, 7-13 minutes) compared with the conventional placement group (median, 5 minutes; 95% confidence interval, 4.0-7.0 minutes). CONCLUSIONS: Placement of transpyloric feeding tubes with the guidance of a noninvasive electromagnetic device significantly increases the time required for accurate placement. Because placement of transpyloric feeding tubes in critically ill children is common practice in many pediatric intensive care units, technology that delays satisfactory placement may be counterproductive in experienced hands. PMID- 22045143 TI - Patients' instability, emergency response, and outcomes in the radiology department. AB - BACKGROUND: Inpatients may be at risk of cardiopulmonary instability during radiologic testing. Calling the medical emergency team is one rescue intervention that brings a team of critical care providers to the unstable patient. Little is known, however, about patients' instability and activations of the medical emergency team in the radiology department (RD-MET). OBJECTIVES: To describe the cause of activation of the RD-MET for hospitalized patients, temporal attributes of RD-MET involvement, characteristics of RD-MET patients, and characteristics associated with good and poor outcomes after RD-MET activation. METHODS: Retrospective pilot study of RD-MET calls for 64 inpatients in a tertiary care hospital during 2009. RESULTS: Reasons for RD-MET activation were 39% neurological, 38% cardiac, and 22% respiratory, and nearly half (42%) occurred during a computed tomography scan. Most RD-MET calls were made between 10 am and noon. RD-MET patients had a mean age of 61 (SD, 19) years; 52% were female, and 89% were white. Admitting diagnoses were most commonly neurological (20%), cardiovascular (16%), and abdominal (16%). The most common comorbid conditions were chronic obstructive pulmonary disease (23%) and diabetes (20%). Half of RD MET inpatients were from a general care unit, and 56% required preexisting oxygen support. After RD-MET involvement, 61% of patients required a higher level of care; 3% died during the MET intervention, and 19% died later in hospitalization. Patients with preexisting comorbid conditions were more likely to have poor outcomes after the RD-MET intervention (P = .001). CONCLUSIONS: RD-MET patients with comorbid conditions, from a general care unit, and at risk for neurological deterioration arrive in the radiology department with potentially underestimated support needs. Greater support in specific time frames and locations may be warranted to improve outcomes. PMID- 22045144 TI - Communication difficulties and psychoemotional distress in patients receiving mechanical ventilation. AB - BACKGROUND: Difficulties in communication in intensive care patients receiving mechanical ventilation are a source of stressful experiences and psychoemotional distress. OBJECTIVES: To examine the association between communication characteristics and psychoemotional distress among patients treated with mechanical ventilation in a medical intensive care unit and to identify factors that may be predictive of psychological outcomes. METHODS: A total of 65 critically ill patients, extubated within the preceding 72 hours, were included in this cross-sectional study. Data were collected by using a structured interview. Separate regression analysis of data on 3 psychoemotional outcomes (psychological distress, fear, and anger) were used for baseline variables, communication characteristics, and stressful experiences. RESULTS: Difficulty in communication was a positive predictor of patients' psychological distress, and length of anesthesia was a negative predictor. Fear and anger were also positively related to difficulty in communication. In addition, the number of communication methods was negatively associated with feelings of fear and anger. Finally, the stressful experiences associated with the endotracheal tube were positively related to feelings of anger. CONCLUSIONS: Patients treated with mechanical ventilation experience a moderate to extreme level of psychoemotional distress because they cannot speak and communicate their needs. Nurses should be aware of the patients' need to communicate. Decreasing stressful experiences associated with the endotracheal tube and implementing more appropriate communication methods may reduce patients' distress. PMID- 22045145 TI - Reducing falls and fall-related injuries in acutely and critically ill patients. PMID- 22045146 TI - New QRS criteria. PMID- 22045147 TI - Bispectral index monitoring in the management of sedation in an intensive care unit patient with locked-in syndrome. AB - Locked-in syndrome is an extremely rare neurological state caused by injury of the ventral pons. The syndrome is characterized by quadriplegia and anarthria with concomitant preservation of cortical function. When a reversible underlying pathological abnormality is identified and managed aggressively, meaningful recovery is possible. Because patients retain consciousness throughout their illness, a dependable method for titrating sedation may improve their quality of life. The case presented suggests that bispectral index monitoring may be a cost effective and reliable method for managing sedation in patients with locked-in syndrome. PMID- 22045148 TI - A simplified score for transfer of patients requiring mechanical ventilation to a long-term care hospital. AB - BACKGROUND: Long-term care hospitals are Medicare providers of postacute care that have a mean length of stay of 25 days or more. Early identification and timely transfer of patients requiring mechanical ventilation to such hospitals may improve the efficiency of inpatient care. OBJECTIVES: To develop a predictive model and a simplified score for use on day 7 of hospitalization to assess whether a patient receiving mechanical ventilation is likely to require an additional 25 days of hospitalization (ie, would qualify for transfer to a long term care hospital). METHODS: A retrospective, cross-sectional study using hospital discharge and billing data from the 2005 Nationwide Inpatient Sample for 54 686 Medicare beneficiaries admitted to US community hospitals who met the study's eligibility criteria. The outcome was overall length of stay (>=32 vs <32 days). Split-sample validation was used. Multivariable survey-logistic regression analyses were performed to assess predictors and probability of the outcome. A simplified score was derived from the final predictive model. RESULTS: The discriminatory power of the predictive model was 0.75 and that of the simplified score was 0.72. The model calibrated well. All predictors were significantly (P < .01) associated with a hospitalization of 32 days or longer; having a tracheostomy was the strongest predictor (odds ratio, 4.74). The simplified scores ranged from -5 to 110 points and were categorized into 3 classes of risk. CONCLUSIONS: Efforts to aid discharge decision making and optimize hospital resource planning could take advantage of our predictive model and the simplified scoring tool. PMID- 22045149 TI - Adverse drug events in intensive care units: a cross-sectional study of prevalence and risk factors. AB - BACKGROUND: Adverse drug events are considered determinants of patient safety and quality of care. OBJECTIVE: To assess the characteristics of adverse drug events in patients admitted to an intensive care unit and determine the impact of severity of illness and nursing workload on the prevalence of the events. METHODS: A cross-sectional survey based on retrospective analysis of a high quality patient data management system for a university-based intensive care unit was used. The prevalence of adverse drug events was measured by using a validated global trigger tool adapted for the critical care environment. Severity was determined by using a validated algorithm. Disease severity and nursing workload were assessed by using validated scoring systems. An investigator blinded to the study and a panel of experts assessed putative serious adverse drug events for each drug taken. Characteristics of patients with and without adverse drug events were compared by using univariate and stepwise multivariate logistic regression. RESULTS: During 175 of 1009 intensive care unit days screened, 230 adverse drug events occurred in 79 patients. The most common events were hypoglycemia, prolonged activated partial thromboplastin time, and hypokalemia. Of the adverse events, 96% were classified as causing temporary harm and 4% as causing complications. Both mean severity of disease and nursing workload were significantly higher on days when 1 or more adverse drug events occurred. CONCLUSION: Adverse drug events were common in intensive care unit patients and were associated with illness severity and nursing workload. PMID- 22045150 TI - Oropharyngeal secretion volume in intubated patients: the importance of oral suctioning. AB - BACKGROUND: Aspiration of secretions that accumulate above the cuff of the endotracheal tube is a risk factor for ventilator-associated pneumonia. Routine suctioning of oropharyngeal secretions may reduce this risk; the recommended frequency for suctioning is unknown. OBJECTIVES: To quantify the volume of secretions suctioned from the oropharynx of critically ill patients at 2 different intervals to assist in identifying a recommended frequency for oropharyngeal suctioning. METHODS: A prospective, repeated measure, single-group design was used. Twenty-eight patients who were orally intubated and treated with mechanical ventilation were enrolled; 2 were extubated during data collection, yielding a sample of 26 patients. The patients were suctioned at baseline with a deep suction catheter, and the volume and weight of secretions were recorded. The procedure was repeated at 2-hour and 4-hour intervals. RESULTS: Most of the patients were male (mean age, 49 years). Three suctioning passes were needed to clear secretions, with a mean time of 48.1 seconds. The mean volume of secretions at the 2-hour interval was 7.5 mL. Five patients required suctioning before the 4 hour interval. For the remaining 21 patients, the volume retrieved was 6.5 mL at the 2-hour interval and 7.5 mL at the 4-hour interval (P = .27). The 5 patients who required extra suctioning had significantly more secretions at the 2-hour interval (11.6 mL vs 6.5 mL; P = .05). CONCLUSIONS: A minimum frequency of oropharyngeal suctioning every 4 hours is recommended. However, more frequent suctioning may be needed in a subset of patients. PMID- 22045151 TI - Coronary artery surgery in octogenarians: evolving strategies for the improvement in early and late results. AB - The purpose of this study was to investigate retrospectively early and late outcomes of coronary artery bypass grafting (CABG) in a large series of octogenarians. We retrospectively reviewed the data of 241 octogenarian patients who underwent CABG between April 2002 and April 2009 at our institution. Mean age was 84.7 +/- 1.8 years. Patients affected by concomitant coexistent organic aortic, mitral, or tricuspid valve disease were excluded from the study. Patients with functional secondary ischemic mitral incompetence were included in the study. The majority of the patients were male. Angina pectoris functional class III/IV accounted for 164 patients (68%). Left ventricular ejection fraction <=35% was diagnosed in 38 patients (15.8%). Early mortality rate was 5.8% (14 patients). Causes of death were cardiac related in 10 patients. Preoperative independent predictors of in-hospital mortality obtained with multivariate analysis were extracardiac arteriopathy, New York Heart Association class III/IV, and previous percutaneous transluminal coronary angioplasty (PTCA). The overall mean follow-up was 41.6 +/- 25.9 months (range 1-87.6 months). Among the 222 contacted survivors, there were 16 (7.2%) deaths during the follow-up. The actuarial survival was 91.9% at 1 year and 83.5% at 5 years. On multivariate analysis, time to late death was adversely affected by preoperative extracardiac arteriopathy and previous PTCA. Advanced age alone should not be a deterrent for CABG if it has been determined that the benefits outweigh the potential risk. A careful selection of optimal candidates, based on the evaluation of their systemic comorbidities, appears mandatory in order to obtain the greatest benefit for these high-risk patients. PMID- 22045152 TI - A free-floating left atrial thrombus develops intermittent entrapment in the mid ventricle during diastole. AB - Free-floating left atrial thrombi are rare. Here we report a case of a 75-year old woman with atrial fibrillation who was admitted for treatment of acute myocardial infarction. A free-floating left atrial thrombus was found incidentally on echocardiography. Ten days after percutaneous coronary intervention, the patient had mild faintness with transient hypotension, and it was found that the left atrial thrombus had developed intermittent entrapment in the mid-ventricle during diastole, with abrupt rebound back to the left atrial cavity during systole. Urgent removal of the thrombus was performed successfully. Although the free-floating thrombus had appeared to be spherical, like a ball thrombus, on echocardiography, the excised thrombus was pedunculated. A cut section revealed a laminated thrombus with an onion-skin-like appearance. PMID- 22045153 TI - Effects of aliskiren on the fibrinolytic system in patients with coronary artery disease receiving angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker. AB - Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. We evaluated the effects of aliskiren on the fibrinolytic system in patients with coronary artery disease who were receiving angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs). We studied 17 patients with coronary artery disease whose systolic blood pressure was more than 130 mmHg despite treatment with ACEIs or ARBs. Aliskiren (150 mg) was added to ACEIs or ARBs, and was continued for 6 weeks. Aliskiren significantly decreased systolic blood pressure (140 +/- 6-128 +/- 8 mmHg, P < 0.001) and plasma renin activity (1.8 +/- 2.3-0.6 +/- 0.9 ng/ml/h, P < 0.01) after 6 weeks. However, it did not affect plasminogen activator inhibitor-1 (28.8 +/- 14.5-30.6 +/- 13.6 ng/ml, P = 0.84), fibrinogen (305 +/- 72 vs 301 +/- 71 mg/dl, P = 0.33), or D-dimer (0.49 +/- 0.24-0.51 +/- 0.28 MUg/ml, P = 0.70) levels. Our data suggested that patients receiving ACEIs or ARBs would not be expected to have any changes in biomarkers of the fibrinolytic system with additional pharmacologic inhibition of the renin-angiotensin-aldosterone system. PMID- 22045154 TI - Sun protective behaviors and vitamin D levels in the US population: NHANES 2003 2006. AB - BACKGROUND: Sun protection is recommended for skin cancer prevention, yet little is known about the role of sun protection on vitamin D levels. Our aim was to investigate the relationship between different types of sun protective behaviors and serum 25(OH)D levels in the general US population. METHODS: Cross-sectional, nationally representative survey of 5,920 adults aged 18-60 years in the US National Health and Nutrition Examination Survey 2003-2006. We analyzed questionnaire responses on sun protective behaviors: staying in the shade, wearing long sleeves, wearing a hat, using sunscreen and SPF level. Analyses were adjusted for multiple confounders of 25(OH)D levels and stratified by race. Our primary outcome measures were serum 25(OH)D levels (ng/ml) measured by radioimmunoassay and vitamin D deficiency, defined as 25(OH)D levels <20 ng/ml. RESULTS: Staying in the shade and wearing long sleeves were significantly associated with lower 25(OH)D levels. Subjects who reported frequent use of shade on a sunny day had -3.5 ng/ml (p (trend) < 0.001) lower 25(OH)D levels compared to subjects who reported rare use. Subjects who reported frequent use of long sleeves had -2.2 ng/ml (p (trend) = 0.001) lower 25(OH)D levels. These associations were strongest for whites, and did not reach statistical significance among Hispanics or blacks. White participants who reported frequently staying in the shade or wearing long sleeves had double the odds of vitamin D deficiency compared with those who rarely did so. Neither wearing a hat nor using sunscreen was associated with low 25(OH)D levels or vitamin D deficiency. CONCLUSIONS: White individuals who protect themselves from the sun by seeking shade or wearing long sleeves may have lower 25(OH)D levels and be at risk for vitamin D deficiency. Frequent sunscreen use does not appear to be linked to vitamin D deficiency in this population. PMID- 22045155 TI - "The impact of cancer scale" version 1: psychometric testing of the Norwegian translation in a heterogeneous sample of cancer survivors. AB - PURPOSE: The impact of cancer scale version 1 (IOC-1) from 2006 has only been tested psychometrically in a heterogeneous sample of 193 American long-term cancer survivors (LTSs). The Norwegian version of IOC-1 compares the psychometric findings of that study with those observed in a heterogeneous sample of 809 Norwegian LTSs. METHODS: We performed exploratory (EFA) and confirmatory (CFA) factor analyses, tests of internal consistency, correlational studies with various other tests and a change over time examination in order to test reliability and validity of the IOC-1. RESULTS: The American factor structure of the IOC-1 with 10 dimensions showed adequate fit with CFA in the Norwegian sample, but internal consistency was insufficient in 2 dimensions. EFA of the Norwegian sample found a 9 factor solution that also showed adequate fit on CFA, and with sufficient internal consistencies for all dimensions. The SF-36 dimensions, anxiety, depression, neuroticism, fatigue and body image all showed low correlations with the positive dimensions of the IOC-1, but higher correlations with the IOC-1 negative dimensions. The IOC-1 dimensions showed considerable stability over time. CONCLUSIONS: In our big heterogeneous sample of LTSs, the Norwegian version of the IOC-1 showed discriminant and concurrent validity, and reliability was supported. PMID- 22045156 TI - Perioperative pregabalin for postoperative pain control and quality of life after major spinal surgery. AB - BACKGROUND: Adequate management of postoperative pain after major spine surgery is often difficult to achieve. We investigated the efficacy of an antineuropathic pain drug, pregabalin (PG), on postoperative pain control and on improvement of quality of life (QoL). METHODS: Sixty patients scheduled for elective decompressive spine surgery were enrolled. One hour before surgery patients received 300 mg of either oral PG or placebo (PL) and 150 mg of PG or PL twice a day for 48 hours postoperatively. During the first 48 postoperative hours, a continuous infusion of morphine 0.01 mg/kg/h and ketorolac tromethamine 2.5 mg/h was administered. Intravenous morphine in 2-mg aliquots up to a maximum of 10 mg was used as rescue therapy. Pain was measured at rest and during movement using a visual analog scale (VAS score), and side effects were recorded in the first hour and at 4, 8, 12, 24, and 48 hours. Three months and 1 year after discharge, patients were contacted by telephone by 1 of the authors to obtain follow-up information using the EuroQoL questionnaire. RESULTS: During the first 8 postoperative hours, VAS scores at rest were significantly lower in the PG group than in the PL group (P<0.05), whereas VAS scores on movement were significantly lower up to 12 hours after the operation in the PG group (P<0.05). The morphine consumption in the PG group was 3+/-2 mg, whereas in the PL group it was 9.5+/ 2.5 mg (P<0.05). Postoperative incidence of constipation and nausea/vomiting was higher in the PL group than in the PG group. No significant differences between the 2 groups were observed with regard to other adverse effects. QoL measures revealed an improvement in outcome, especially in movement and in pain dimensions in both groups; however, at 3 months, subjective qualification of overall QoL was better in the PG group than in the PL group. There were no differences in QoL after the 1-year follow-up period. CONCLUSIONS: Perioperative PG administration reduces early postsurgical pain at rest and particularly during movement after major spine surgery with less opioid consumption, and it seems to influence the improvement of overall QoL 3 months after surgery. PMID- 22045157 TI - On a not-dead horse: CPP deserves more respect. PMID- 22045159 TI - Screening for colorectal cancer: established and emerging modalities. AB - It has been estimated that >95% of cases of colorectal cancer (CRC) would benefit from curative surgery if diagnosis was made at an early or premalignant polyp stage of disease. Over the past 10 years, most developed nation states have implemented mass population screening programs, which are typically targeted at the older (at-risk) age group (>50-60 years old). Conventional screening largely relies on periodic patient-centric investigation, particularly involving colonoscopy and flexible sigmoidoscopy, or else on the fecal occult blood test. These methods are compromised by either low cost-effectiveness or limited diagnostic accuracy. Advances in the development of diagnostic molecular markers for CRC have yielded an expanding list of potential new screening modalities based on investigations of patient stool (for colonocyte DNA mutations, epigenetic changes or microRNA expression) or blood specimens (for plasma DNA mutations, epigenetic changes, heteroplasmic mitochondrial DNA mutations, leukocyte transcriptome profile, plasma microRNA expression or protein and autoantibody expression). In this Review, we present a critical evaluation of the performance data and relative merits of these various new potential methods. None of these molecular diagnostic methods have yet been evaluated beyond the proof-of principle and pilot-scale study stage and it could be some years before they replace existing methods for population screening in CRC. PMID- 22045160 TI - Diagnosis: Intestinal inflammation--key to complications in cirrhosis? PMID- 22045162 TI - Comparative molecular and microbiological diagnosis of 19 infective endocarditis cases in which causative microbes were identified by PCR-based DNA sequencing from the excised heart valves. AB - Infective endocarditis (IE) is traditionally diagnosed by microbiological analysis of blood cultures, following which therapeutic antibiotics are chosen based on antimicrobial sensitivity tests. However, such conventional techniques do not always lead to an accurate etiological diagnosis. Recently, PCR analysis of the 16S rRNA gene has been employed to identify organisms isolated from excised heart valves. In this study, we analyzed 19 valve samples from patients with confirmed IE, as identified by Duke's criteria. Using broad-range PCR amplification, followed by direct gene sequencing, pathological agents were identified in all samples. Although blood cultures yielded negative results in 4 cases, PCR analysis of valve samples showed positive identification of causative organisms. In 3 cases, there was a difference between blood culture and PCR in identification of pathological agents, which are likely to be misidentified by the conventional method based on the phenotypic database. Postoperative antibiotics were chosen considering the severity of lesions and the results of PCR, Gram staining, and valve cultures. All patients were cured without relapse. The broad-range PCR method was therefore beneficial for the management of IE because it enabled us to identify pathogens directly from the site of infection, even organisms that were difficult to culture or likely to be misidentified by the conventional culture method. Identification of the agents provided precise knowledge of the microbiological spectrum involved in the cases of IE. PMID- 22045161 TI - Paradoxical roles of alveolar macrophages in the host response to Cryptococcus neoformans. AB - Cryptococcus neoformans (Cn) is a fungal pathogen that is a serious health threat to immunocompromised individuals. Upon environmental exposure, infectious fungal propagules are inhaled into the host's lungs. The anticryptococcal actions of alveolar macrophages (AM), the predominant host phagocyte of the innate immune system in the lungs, are fundamental in determining whether containment and clearance of the pathogen occurs by the development of an adapted immune response or whether infection is established and progresses to disease. However, the fungus is also capable of surviving the antimicrobial actions of AM and exploits these host phagocytes to establish infection and exacerbate disease. In addition, there is evidence suggesting that cryptococcosis may occur following reactivation of latent cryptococcal infection. Currently, the role of AM and the fungal factors contributing to latent cryptococcosis are unknown. This review examines the AM-Cn interaction and how it affects the development of pulmonary disease with a focus on host and pathogen factors enabling latency to occur. PMID- 22045163 TI - Adalimumab treatment may replace or enhance the activity of steroids in steroid refractory tuberculous meningitis. AB - We describe a paradoxical response involving the central nervous system in a patient with steroid-refractory tuberculous meningitis that was unresponsive to systemic corticosteroids but was improved with adalimumab. The immunomodulatory effect of tumor necrosis factor inhibitors may have a role in replacing or enhancing the activity of steroids in the management of steroid-refractory tuberculous meningitis. PMID- 22045164 TI - Severe pneumococcal community-acquired pneumonia admitted to medical Tunisian ICU. AB - Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP). There are no available data about this disease in Tunisian intensive care patients. The objective of this study is to describe the clinical and microbiological features of pneumococcal CAP and determine the prognostic factors. This is a retrospective cohort study of all pneumococcal CAP cases hospitalized in the medical intensive care unit (ICU) of Hospital A. Mami of Ariana (Tunisia) between January 1999 and August 2008. Included were 132 patients (mean age, 49.5 years; 82.6% males); 30 patients had received antimicrobial treatment before hospital admission. The mean of the Simplified Acute Physiology Score II was 32.9. All patients had an acute respiratory failure; 34 patients (25.8%) had pneumococcal bacteremic CAP. Among the isolated strains, 125 antimicrobial susceptibility tests were performed. The use of the new Clinical and Laboratory Standards Institute breakpoints for susceptibility when testing penicillin against S. pneumoniae showed that all isolated strains were susceptible to penicillin. The mortality rate was 25%. The need of mechanical ventilation at admission [odds ratio (OR), 3.4; 95% confidence interval (CI), 1.67-6.94; P = 0.001), Sepsis-related Organ Failure Assessment (SOFA) score at admission >=4 (OR, 3.1; 95% CI, 1.56-6.13; P = 0.001), and serum creatinine at admission >=102 MUmol/l (OR, 1.8; 95% CI, 1.02-3.17; P = 0.043) were independent factors related to ICU mortality. In conclusion, pneumococcal CAP requiring hospitalization in the ICU is associated with high mortality. All isolated stains were susceptible to penicillin. PMID- 22045165 TI - PdCl2(dppf)-catalyzed in situ coupling of 2-hydroxypyridines with aryl boronic acids mediated by PyBroP and the one-pot chemo- and regioselective construction of two distinct aryl-aryl bonds. AB - We present a PdCl(2)(dppf)-catalyzed synthesis of 2-arylated pyridine derivatives via the in situ coupling of 2-OH pyridines and boronic acids mediated by PyBroP. In addition, the highly chemo- and regioselective construction of two different aryl-aryl bonds via a one-pot operation has also been demonstrated by the orthogonal use of this method with the Ni-catalyzed Suzuki-Miyaura coupling of phenols. PMID- 22045166 TI - Resuscitative effect of hyperoxia fluid on high-altitude hemorrhagic shock in rats and antishock mechanisms. AB - Pathophysiological characteristics of hemorrhagic shock at high altitude are different from that at plain which involve severe injury, high mortality, difficult treatment and compromised liquid tolerance. High-altitude pulmonary/cerebral edema and multiple-organ dysfunction render the conventional treatment ineffective. Herein, we evaluated the resuscitation effects of hyperoxia solution on high-altitude hemorrhagic shock in rats. For this purpose, a rat model of high-altitude (3,658 m) hemorrhagic shock was established on the plateau and hyperoxia solution (4 ml/kg) was infused through external jugular vein for resuscitation at 60 min post-hemorrhage. Blood pressure, blood gas, left and right ventricular pressure, lung and brain water content, survival time, survival rate at 2 h, levels of inflammatory cytokines and free oxygen radicals in blood and tissue were determined. After resuscitation with hyperoxia solution, blood pressure, arterial oxygen partial pressure, left and right ventricular systolic pressure, +/-dp/dt max, survival time and rate were significantly increased. Lung and brain water content were unchanged, malondialdehyde activity in lung, brain and plasma and levels of TNF-alpha, IL-1, IL-6, and endothelin were significantly decreased. Besides, CGRP was elevated with reduced injury and improved lung and kidney functions. Concludingly, resuscitation with hyperoxia solution is feasible and more effective than other classical liquids, making it the first choice of treatment for high-altitude hemorrhagic shock. PMID- 22045167 TI - Solution behavior of iron(III) and iron(II) porphyrins in DMSO and reaction with superoxide. Effect of neighboring positive charge on thermodynamics, kinetics and nature of iron-(su)peroxo product. AB - The solution behavior of iron(III) and iron(II) complexes of 5(4),10(4),15(4),20(4)-tetra-tert-butyl-5,10,15,20-tetraphenylporphyrin (H(2)tBuTPP) and the reaction with superoxide (KO(2)) in DMSO have been studied in detail. Applying temperature and pressure dependent NMR studies, the thermodynamics of the low-spin/high-spin equilibrium between bis- and mono-DMSO Fe(II) forms have been quantified (K(DMSO) = 0.082 +/- 0.002 at 298.2 K, DeltaH degrees = +36 +/- 1 kJ mol(-1), DeltaS degrees = +101 +/- 4 J K(-1) mol(-1), DeltaV degrees = +16 +/- 2 cm(3) mol(-1)). This is a key activation step for substitution and inner-sphere electron transfer. The superoxide binding constant to the iron(II) form of the studied porphyrin complex was found to be (9 +/- 0.5) * 10(3) M(-1), and does not change significantly in the presence of the externally added crown ether in DMSO (11 +/- 4) * 10(3) M(-1). The rate constants for the superoxide binding (k(on) = (1.30 +/- 0.01) * 10(5) M(-1) s(-1)) and release (k(off) = 11.6 +/- 0.7 s(-1)) are not affected by the presence of the external crown ether in solution. The resulting iron(II)-superoxide adduct has been characterized (mass spectrometry, EPR, high-pressure UV/Vis spectroscopy) and upon controlled addition of a proton source it regenerates the starting iron(II) complex. Based on DFT calculations, the reaction product without neighboring positive charge has iron(II)-superoxo character in both high-spin side-on and low-spin end-on forms. The results are compared to those obtained for the analogous complex with covalently attached crown ether, and more general conclusions regarding the spin-state equilibrium of iron(II) porphyrins, their reaction with superoxide and the electronic structure of the product species are drawn. PMID- 22045168 TI - Brief cognitive assessment in the early stages of Parkinson disease. AB - INTRODUCTION: Cognitive dysfunction is an integral part of the Parkinson disease (PD) symptom spectrum. Early detection of cognitive dysfunction could help to delineate prevention strategies. Our main objective was to study the validity of brief cognitive tests, the Frontal Assessment Battery (FAB) and Mini-Mental State Examination (MMSE), as cognitive screening tools for detecting global and executive cognitive deficits in early stages of PD, as compared to a healthy control population. METHODS: We evaluated 75 early-stage PD patients and 45 healthy age-matched and education-matched controls with the MMSE (global test) and FAB (frontal test), and compared total and subtest scores. We evaluated PD motor function with the Unified Parkinson Disease Rating Scale Part III. We assessed the relationship between cognitive and motor variables. RESULTS: Frontal and global cognitive dysfunction was significantly more frequent in PD patients. PD patients scored significantly lower on FAB total and similarities, motor series, and conflicting instructions scores, and on the MMSE total, visuoconstructive, and memory scores. MMSE scores correlated significantly with Unified Parkinson Disease Rating Scale part III total score, speech, and bradykinesia scores. CONCLUSIONS: Early-stage PD patients present with frontal, memory, and visuoconstructive deficits in brief cognitive tests. Our results suggest that these brief bedside tests are useful for cognitive deficit screening in the early stages of PD. Our study did not account for the influence of depression in cognition. This constitutes a limitation, because many PD patients have depressive symptoms, which some studies have shown can be related to cognitive dysfunction. PMID- 22045169 TI - The history and anatomy of urologic lymphadenectomy. AB - The history of urologic lymphadenectomy is rich and diverse. Our current understanding of its use and benefits is a product of the hard work of numerous physicians and scientists from many nations. Standard dissection templates for the various urologic malignancies are based on a complete understanding of the anatomy of the lymphatic system, which has developed immensely since Hippocrates first described the white blood of the lymphatic system while performing an axillary dissection. It is hoped that the next 100 years will bring even greater comprehension of its value and utility. PMID- 22045170 TI - Role of lymphadenectomy for prostate cancer: indications and controversies. AB - Pelvic lymph node dissection is the only reliable technique to detect low-volume lymph node involvement in prostate cancer. Extended lymph node dissections that include the internal iliac chain in addition to the external iliac and obturator packets have shown a significantly higher proportion of patients to have lymphatic involvement than previously recognized. The improved staging afforded by a more extended dissection raises several questions. Addressing these questions is the focus of this review. PMID- 22045171 TI - Lymphadenectomy for bladder cancer: indications and controversies. AB - Pelvic lymph node dissection (PLND) at the time of cystectomy remains the most accurate method of staging and can have a positive impact on cancer control, and there is general agreement as to its necessity at the time of surgery. There is, however, a lack of consensus regarding the terminology of PLND and controversy concerning the optimal extent of lymph node dissection, especially because recent investigations have suggested a survival benefit with extended PLND. PMID- 22045172 TI - Feasibility of minimally invasive lymphadenectomy in bladder and prostate cancer surgery. AB - With the rapid and widespread adoption of minimally invasive procedures (laparoscopic and robotic) for the treatment of prostate and bladder cancers in the last decade, concerns have been raised regarding whether the technique can emulate the time-tested gold standard open procedures. This article briefly reviews the indications for lymph node dissection for bladder and prostate cancer, and reviews the role of extended lymphadenectomy in each procedure. Much of the focus of this review is on minimally invasive approaches and the technical aspects of the procedures, the feasibility of the robotic technique, and early oncologic outcomes. PMID- 22045173 TI - The role of lymph node dissection in renal cell carcinoma. AB - The role of lymph node dissection (LND) in the staging and treatment of renal cell carcinoma has long been a topic of debate. The controversy has focused on whether LND is purely an adjunctive staging procedure or has a therapeutic role in the management of this disease. Potential benefits include enhanced staging, better selection for adjuvant therapies/clinical trials, a decrease in recurrence rates, and improved disease-specific and overall survival. This article reviews the available literature on LND in renal cell carcinoma and discusses the potential benefits of aggressive surgical resection in select high-risk patients. PMID- 22045174 TI - The emerging role of lymphadenectomy in upper tract urothelial carcinoma. AB - Within the last decade, there has been an increased focus on lymphadenectomy or lymph node dissection (LND) in patients with upper tract urothelial carcinoma (UTUC). Although the data with regards to LND in UTUC are sparse, investigators are beginning to evaluate the role and define the anatomy to understand how LND may affect outcomes in patients with UTUC. This article reviews the history of LND for UTUC, outlines the relative anatomy, and evaluates the arguments and evidence for, and against, LND in patients with UTUC. PMID- 22045175 TI - The role of lymphadenectomy for testicular cancer: indications, controversies, and complications. AB - Retroperitoneal lymphadenectomy remains an integral component in the multidisciplinary management of testicular cancer. Through the evolution of the procedure, continued refinements have led to diagnostic and therapeutic benefits as well as improvements in perioperative and long-term morbidity. This article discusses the surgical management of testicular cancer, specifically addressing the indications, controversies, and complications of retroperitoneal lymph node dissection for both low-stage and high-stage disease. PMID- 22045176 TI - Minimally invasive retroperitoneal lymph node dissection for testicular cancer. AB - Testicular cancer is the most common solid organ malignancy in young men between the ages of 15 and 35. Although much of this increase in survival can be attributed to improvements in systemic chemotherapy, surgery retains a critical role in the diagnostic and therapeutic management of testicular cancer. Laparoscopic retroperitoneal lymph node dissection is an effective staging and therapeutic procedure in patients with low-stage testicular cancer. It is an attractive alternative to the open approach, with faster recovery, improved cosmesis, and reduced post-operative morbidity driving its application. In experienced hands, it can be used in postchemotherapy patients. PMID- 22045177 TI - Lymphadenectomy in penile cancer. AB - In contrast to many cancers, squamous cell carcinoma of the penis can be cured despite the presence of lymph node metastases. This characteristic is shared with testicular cancer. But unlike testicular cancer, penile carcinoma is not chemosensitive and, therefore, the focus of management has been on surgery. This article addresses all aspects of imaging and minimally invasive methods of detecting lymph node involvement. It focuses on the indications of surgical management of the regional nodes, the extent of the surgery, and its complications. Also, neoadjuvant therapy is covered. PMID- 22045178 TI - Novel imaging modalities for lymph node imaging in urologic oncology. AB - Accurate lymph node staging in genitourinary (GU) malignancies is important for planning an appropriate treatment and establishing an accurate prognosis. This article discusses the novel imaging techniques for detection of metastases in various GU malignancies, including prostate, bladder, penile, and testicular cancers. Discussion includes nuclear medicine techniques of (18)F fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), (11)C-choline and (18)F-choline PET/CT, and ProstaScint scanning, as well as sentinel lymph node mapping. Magnetic resonance (MR) techniques include lymphotropic nanoparticle-enhanced MR imaging and diffusion-weighted MR imaging. PMID- 22045179 TI - Lymphadenectomy in urologic oncology: pathologic considerations. AB - Lymphadenectomy (LAD) is an important staging and treatment modality of oncologic surgery. LAD in genitourinary malignancies presents inherent difficulties to the urologist and pathologist because of the differences in anatomic sites and primary histologic type. This review focuses on pathologic evaluation and how communication between urologist and pathologist is necessary to provide optimal care. Recommendations covering general specimen submission and processing are discussed, as well as more specific recommendations concerning the kidney, upper urinary tract, urinary bladder, prostate, testes, and penis. Emerging areas of prognostic significance and the impact that improved molecular techniques are contributing to diagnostic interpretation are highlighted. PMID- 22045180 TI - Role of radiation therapy for the treatment of lymph nodes in urologic malignancies. AB - Radiation therapy (RT) represents an important therapeutic component in the management of genitourinary (GU) malignancies. RT is used to treat patients with proven involvement of the regional lymph nodes or delivered electively to patients at risk for occult regional lymph node metastases. Advances in treatment planning and delivery of various types of RT provide the technology to precisely plan, target, and deliver RT with the goal of optimizing the radiation dose to the target while sparing normal tissue. This article provides an overview of the modalities, indications, and techniques of RT for treatment of the lymphatic basins in GU malignancies. PMID- 22045181 TI - Complications of lymphadenectomy in urologic surgery. AB - Lymphadenectomy in urologic surgery provides accurate staging and may be therapeutic in some patients with lymph node metastases. In addition to the associated cost, pelvic lymph node dissection (PLND) has the potential for morbidity. This article focuses on the complications associated with PLND, including lymphocele, thromboembolic events, ureteral injury, nerve injury, vascular injury, and lymphedema. With improvements in surgical technique and perioperative care, the morbidity associated with lymphadenectomy may be minimized. PMID- 22045182 TI - Lymphadenectomy in urologic oncology: indications, controversies and complications. Preface. PMID- 22045183 TI - TYRP1 mRNA expression in melanoma metastases correlates with clinical outcome. AB - BACKGROUND: Clinical outcome of patients with high-risk melanoma cannot be reliably predicted on the basis of classical histopathological examination. Our study aimed to determine in melanoma metastases a gene expression profile associated with patient survival, and to identify and validate marker(s) of poor clinical outcome. METHODS: Skin and lymph node metastases from melanoma patients (training population) were used to identify candidate prognostic marker(s) based on DNA microarray analysis. Additional skin metastases (validation population) were used to assess the prognostic value of the first ranked gene by real-time PCR. RESULTS: We performed microarray analysis in the training population and generated a list of 278 probe sets associated with a shorter survival. We used the first ranked gene, tyrosinase-related protein 1 (TYRP1), further measured its expression in the validation population by real-time PCR and found it to be significantly correlated with distant metastasis-free survival (DMFS), overall survival (OS) and Breslow thickness. We also found that it was fairly well conserved in the course of the disease regardless of the delay to metastasis occurrence. Finally, although Tyrp1 protein (immunohistochemistry (IHC)) was only detected in about half of the samples, we showed that its expression also correlated with Breslow thickness. CONCLUSION: Our data indicate that TYRP1 mRNA expression level, at least in skin metastases, is a prognostic marker for melanoma, and is particularly useful when prognostic pathology parameters at the primary lesion are lacking. Its conserved expression further supports its use as a target for therapy. PMID- 22045184 TI - Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. AB - BACKGROUND: Ascertainment of cases and disease classification is an acknowledged problem for epidemiological research into haematological malignancies. METHODS: The Haematological Malignancy Research Network comprises an ongoing population based patient cohort. All diagnoses (paediatric and adult) across two UK Cancer Networks (population 3.6 million, >2000 diagnoses annually, socio-demographically representative of the UK) are made by an integrated haematopathology laboratory. Diagnostics, prognostics, and treatment are recorded to clinical trial standards, and socio-demographic measures are routinely obtained. RESULTS: A total of 10,729 haematological malignancies (myeloid=2706, lymphoid=8023) were diagnosed over the 5 years, that is, from 2004 to 2009. Descriptive data (age, sex, and deprivation), sex-specific age-standardised (European population) rates, and estimated UK frequencies are presented for 24 sub-types. The age of patients ranged from 4 weeks to 99 years (median 70.6 years), and the male rate was more than double the female rate for several myeloid and lymphoid sub-types, this difference being evident in both children and adults. No relationship with deprivation was detected. CONCLUSION: Accurate population-based data on haematological malignancies can be collected to the standard required to deliver reproducible results that can be extrapolated to national populations. Our analyses emphasise the importance of gender and age as disease determinants, and suggest that aetiological investigations that focus on socio-economic factors are unlikely to be rewarding. PMID- 22045185 TI - MicroRNA-15b is induced with E2F-controlled genes in HPV-related cancer. AB - BACKGROUND: MicroRNAs (miRNAs) are important regulators of cellular processes and are found to be deregulated in many cancers. We here analysed the miRNA expression in anal carcinomas. In a previous study, we found that our anal carcinoma tumours were divided into two groups based on the expression of E2F regulated genes. Therefore, we searched for miRNAs that could reproduce this grouping. METHODS: A global screen of the miRNA population was performed using real-time quantitative PCR (RT-qPCR) array methods and differentially expressed miRNAs were identified. Real-time-qPCR was used to verify the expression levels of selected miRNAs and genes in a larger collection of biopsies. A siRNA-mediated knockdown of human papilloma virus (HPV)16 E7 in a cervical cell line was performed to assess the effect of E7 on miR-15b. RESULTS: The grouping of tumours into two groups based on the expression of E2F-controlled genes was confirmed in a larger collection of anal carcinoma tumours. The expression of miR-15b was shown to be highly correlated with that of five selected E2F-induced genes (CCNA2, CCNB1, CCNB2, MSH6 and MCM7). A knockdown of HPV16 E7 resulted in decreased levels of miR-15b in Ca Ski cells. CONCLUSION: MiR-15b expression correlates with E2F-regulated genes in anal carcinoma and appears to be part of the E2F-regulatory network. PMID- 22045186 TI - Stromal interaction essential for vascular endothelial growth factor A-induced tumour growth via transforming growth factor-beta signalling. AB - BACKGROUND: High vascular endothelial growth factor (VEGFA) levels at the time of diagnosis confer a worse prognosis to multiple malignancies. Our aim was to investigate the role of VEGFA in promoting tumour growth through interaction with its environment. METHODS: HL-60 cells were transduced with VEGFA165 or control vector using retroviral constructs. Control cells (n=7) or VEGFA165 cells (n=7) were subcutaneously injected into NOD/SCID mice. Immunohistochemistry of markers for angiogenesis (CD31) and cell proliferation (Ki67) and gene expression profiling of tumours were performed. Paracrine effects were investigated by mouse specific cytokine arrays. RESULTS: In vivo we observed a twofold increase in tumour weight when VEGFA165 was overexpressed (P=0.001), combined with increased angiogenesis (P=0.002) and enhanced tumour cell proliferation (P=0.001). Gene expression profiling revealed human genes involved in TGF-beta signalling differentially expressed between both tumour groups, that is, TGFBR2 and SMAD5 were lower expressed whereas the inhibitory SMAD7 was higher expressed with VEGFA165. An increased expression of mouse-derived cytokines IFNG and interleukin 7 was found in VEGFA165 tumours, both described to induce SMAD7 expression. CONCLUSION: These results suggest a role for VEGFA-driven tumour growth by TGF beta signalling inhibition via paracrine mechanisms in vivo, and underscore the importance of stromal interaction in the VEGFA-induced phenotype. PMID- 22045187 TI - Methylenetetrahydrofolate reductase genetic polymorphisms and toxicity to 5-FU based chemoradiation in rectal cancer. AB - BACKGROUND: There is a large degree of variation in tumour response and host toxicities associated with neoadjuvant chemoradiation for rectal cancer patients. We performed a complimentary pharmacogenetic study to investigate germline polymorphisms of genes involved in 5-fluorouracil (5-FU) and irinotecan pathways and their potential association with clinical outcomes and toxicities from neoadjuvant chemoradiation in patients with rectal cancer treated in a prospective genotype-directed study. METHODS: The germline DNA of 131 patients was genotyped for 10 variants in TYMS, MTHFR, DPYD, UGT1A1, ABCC1 and SLCO1B1 genes. Ninety-six patients were treated with 5-FU/radiotherapy (RT) and 35 received 5-FU/RT/irinotecan. Relationships between genetic variants and adverse events, tumour response, overall and disease-free survivals were assessed. RESULTS: MTHFR 1298A>C and MTHFR diplotypes (for 677C>T and 1298A>C) were associated with chemoradiation-related toxicity when 5-FU was used alone. MTHFR haplotypes (677C-1298C) and diplotypes (CA-TA and TA-TA) showed, respectively, a protective and a negative effect on the incidence of severe diarrhoea or mucositis. No association was observed between genetic markers and drug response. CONCLUSION: MTHFR polymorphisms can potentially predict toxicity in patients treated with 5-FU as a single chemotherapeutic drug. PMID- 22045188 TI - Rapid in vivo testing of drug response in multiple myeloma made possible by xenograft to turkey embryos. AB - BACKGROUND: The best current xenograft model of multiple myeloma (MM) in immune deficient non-obese diabetic/severe-combined immunodeficient mice is costly, animal maintenance is complex and several weeks are required to establish engraftment and study drug efficacy. More practical in vivo models may reduce time and drug development cost. We recently described a rapid low-cost xenograft model of human blood malignancies in pre-immune turkey. Here, we report application of this system for studying MM growth and the preclinical assessment of anticancer therapies. METHODS: Cell lines and MM patient cells were injected intravenously into embryonic veins on embryonic day 11 (E11). Engraftment of human cells in haematopoietic organs was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, flow cytometry and circulating free light chain. RESULTS: Engraftment was detected after 1 week in all embryos injected with cell lines and in 50% of those injected with patient cells. Injection of bortezomib or lenalinomide 48 h after cell injection at therapeutic levels that were not toxic to the bone marrow dramatically reduced MM engraftment. CONCLUSION: The turkey embryo provides a practical, xenograft system to study MM and demonstrates the utility of this model for rapid and affordable testing therapeutics in vivo. With further development, this model may enable rapid, inexpensive personalised drug screening. PMID- 22045189 TI - Chemoresistant colorectal cancer cells and cancer stem cells mediate growth and survival of bystander cells. AB - BACKGROUND: Recent studies suggest that cancer stem cells (CSCs) mediate chemoresistance, but interestingly, only a small percentage of cells in a resistant tumour are CSCs; this suggests that non-CSCs survive by other means. We hypothesised that chemoresistant colorectal cancer (CRC) cells generate soluble factors that enhance survival of chemonaive tumour cells. METHODS: Chemoresistant CRC cells were generated by serial passage in oxaliplatin (Ox cells). Conditioned media (CM) was collected from parental and oxaliplatin-resistant (OxR) cells. CRC cells were treated with CM and growth and survival were assessed. Tumour growth rates were determined in nude mice after cells were treated with CM. Mass spectrometry (MS) identified proteins in CM. Reverse phase protein microarray assays determined signalling effects of CM in parental cells. RESULTS: Oxaliplatin-resistant CM increased survival of chemo-naive cells. CSC CM also increased growth of parental cells. Parental and OxR mixed tumours grew larger than tumours composed of parental or OxR cells alone. Mass spectrometry detected unique survival-promoting factors in OxR CM compared with parental CM. Cells treated with OxR CM demonstrated early phosphorylation of EGFR and MEK1, with later upregulation of total Akt .We identified progranulin as a potential mediator of chemoresistance. CONCLUSION: Chemoresistant tumour cells and CSCs may promote resistance through soluble factors that mediate survival in otherwise chemosensitive tumour cells. PMID- 22045190 TI - Novel diagnostic value of circulating miR-18a in plasma of patients with pancreatic cancer. AB - BACKGROUND: Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in the plasma/serum. We hypothesised that miR-18a in the plasma is a potential biomarker in patients with pancreatic cancer. METHODS: miR-18a is located in the miR-17-92 cluster and reported to be highly expressed in pancreatic cancer tissues. This study was divided into three parts: (1) Confirmation of higher miR-18a levels in primary pancreatic cancer tissues and cell lines than in normal pancreatic tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT-PCR by comparing plasma results obtained from 36 patients with pancreatic cancer and from 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with pancreatic cancer. RESULTS: (1) The expression of miR-18a was significantly higher in pancreatic cancer tissues (P=0.012) and pancreatic cancer cell lines (P=0.015) than in normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in pancreatic cancer patients than in controls (P<0.0001). The value of the area under the receiver-operating characteristic curve (AUC) was 0.9369. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than in preoperative samples (P=0.0077). CONCLUSION: Circulating miR-18a might provide new complementary tumour markers for pancreatic cancer. PMID- 22045191 TI - A microRNA gene expression signature predicts response to erlotinib in epithelial cancer cell lines and targets EMT. AB - BACKGROUND: Treatment with epidermal growth factor receptor (EGFR) inhibitors can result in clinical response in non-small-cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) for some unselected patients. EGFR and KRAS mutation status, amplification of EGFR, or gene expression predictors of response can forecast sensitivity to EGFR inhibition. METHODS: Using an NSCLC cell line model system, we identified and characterised microRNA (miRNA) gene expression that predicts response to EGFR inhibition. RESULTS: Expression of 13 miRNA genes predicts response to EGFR inhibition in cancer cell lines and tumours, and discriminates primary from metastatic tumours. Signature genes target proteins that are enriched for epithelial-to-mesenchymal transition (EMT) genes. Epithelial-to-mesenchymal transition predicts EGFR inhibitor resistance and metastatic behaviour. The EMT transcription factor, ZEB1, shows altered expression in erlotinib-sensitive NSCLC and PDAC, where many signature miRNA genes are upregulated. Ectopic expression of mir-200c alters expression of EMT proteins, sensitivity to erlotinib, and migration in lung cells. Treatment with TGFbeta1 changes expression of signature miRNA and EMT proteins and modulates migration in lung cells. CONCLUSION: From these data, we hypothesise that the tumour microenvironment elicits TGFbeta1 and stimulates a miRNA gene expression program that induces resistance to anti-EGFR therapy and drives lung tumour cells to EMT, invasion, and metastasis. PMID- 22045192 TI - Inhibition of hyaluronan retention by 4-methylumbelliferone suppresses osteosarcoma cells in vitro and lung metastasis in vivo. AB - BACKGROUND: Hyaluronan (HA) plays crucial roles in the tumourigenicity of many types of malignant tumours. 4-Methylumbelliferone (MU) is an inhibitor of HA synthesis. Several studies have shown its inhibitory effects on malignant tumours; however, none have focused on its effects on osteosarcoma. METHODS: We investigated the effects of MU on HA accumulation and tumourigenicity of highly metastatic murine osteosarcoma cells (LM8) that have HA-rich cell-associated matrix, and human osteosarcoma cell lines (MG-63 and HOS). RESULTS: In vitro, MU inhibited HA retention, thereby reducing the formation of functional cell associated matrices, and also inhibited cell proliferation, migration, and invasion. Akt phosphorylation was suppressed by MU (1.0 mM). In vivo, although MU showed only a mild inhibitory effect on the growth of the primary tumour, it markedly inhibited (75% reduction) the development of lung metastasis. Hyaluronan retention in the periphery of the primary tumour was markedly suppressed by MU. CONCLUSION: These findings suggested that MU suppressed HA retention and cell associated matrix formation in osteosarcoma cells, resulting in a reduction of tumourigenicity, including lung metastasis. 4-Methylumbelliferone is a promising therapeutic agent targeting both primary tumours and distant metastasis of osteosarcoma, possibly via suppression of HA retention. PMID- 22045193 TI - Role of histological type on surgical outcome and survival following radical primary tumour debulking of epithelial ovarian, fallopian tube and peritoneal cancers. AB - BACKGROUND: To assess the clinical impact of the two histological types as designated in the proposed model for ovarian tumourigenesis in primary epithelial ovarian, fallopian tube or peritoneal cancer (EOC) patients. METHODS: All consecutive EOC patients (n=632) after primary tumour debulking in our institution (09/2000-08/2010) were classified into one of two groups: type I tumours (n=100; 15.8%) composed of low-grade serous, low-grade endometrioid, clear cell, mucinous and transitional carcinomas; and Type II tumours (n=532; 84.1%) composed of high-grade serous, high-grade endometrioid, undifferentiated and malignant mixed-mesodermal tumours. Kaplan-Meier and logistic/Cox-regression analyses were performed to assess the impact of histological type on surgical outcome and survival. RESULTS: Type II patients had a significantly higher incidence of advanced disease (FIGO III/IV) than Type I patients (79.8% vs 38%, respectively; P<0.001). Median CA125 values (438 vs 93 U ml(-1); P=0.001); operative time (258 vs 237 min; P=0.001); and incidence of incomplete tumour resection (34.4% vs 15%; P<0.001) were significantly higher in patients with Type II. During a mean follow-up time of 23 months (range: 1-106), 17% of patients with type I vs 34.8% of patients with type II tumours relapsed and/or died (P<0.001). Overall survival (P=0.021) and progression-free survival (P=0.003) were also significantly higher in patients with type I tumours. Multivariate analysis, while identifying postoperative tumour residuals, positive lymph nodes and extrapelvic dissemination as independent predictors of survival, failed to demonstrate any prognostic significance of histological type. CONCLUSION: Type I EOC patients appear to present at earlier stages have significantly higher survival and more optimal surgical outcome compared with type II patients. However, in advanced stages, histology loses significance as an independent prognosticator. PMID- 22045194 TI - Combined effect of low-penetrant SNPs on breast cancer risk. AB - BACKGROUND: Although many low-penetrant genetic risk factors for breast cancer have been discovered, knowledge about the effect of multiple risk alleles is limited, especially in women <50 years. We therefore investigated the association between multiple risk alleles and breast cancer risk as well as individual effects according to age-approximated pre- and post-menopausal status. METHODS: Ten previously described breast cancer-associated single-nucleotide polymorphisms (SNPs) were analysed in a joint European biobank-based study comprising 3584 breast cancer cases and 5063 cancer-free controls. Genotyping was performed using MALDI-TOF mass spectrometry, and odds ratios were estimated using logistic regression. RESULTS: Significant associations with breast cancer were confirmed for 7 of the 10 SNPs. Analysis of the joint effect of the original 10 as well as the statistically significant 7 SNPs (rs2981582, rs3803662, rs889312, rs13387042, rs13281615, rs3817198 and rs981782) found a highly significant trend for increasing breast cancer risk with increasing number of risk alleles (P-trend 5.6 * 10(-20) and 1.5 * 10(-25), respectively). Odds ratio for breast cancer of 1.84 (95% confidence interval (CI): 1.59-2.14; 10 SNPs) and 2.12 (95% CI: 1.80-2.50; 7 SNPs) was seen for the maximum vs the minimum number of risk alleles. Additionally, one of the examined SNPs (rs981782 in HCN1) had a protective effect that was significantly stronger in premenopausal women (P-value: 7.9 * 10(-4)). CONCLUSION: The strongly increasing risk seen when combining many low-penetrant risk alleles supports the polygenic inheritance model of breast cancer. PMID- 22045195 TI - MRI graduation of osseous reaction and drill hole consolidation after arthroscopic Bankart repair with PLLA anchors and the clinical relevance. AB - PURPOSE: Conventionally, radiography studies revealed prolonged glenoidal drill hole visibilities with an unclear influence to the clinical outcome after arthroscopic Bankart repair using Poly-Laevo-Lactic-Acid (PLLA) anchors. The primary aim of the present study was the separated assessment of drill hole consolidation (DHC) and the concomitant osseous reaction (OR) of the glenoidal bio-degradation process in new specific magnetic resonance grading systems. In accordance with the specific DHC and the OR graduation, the clinical relevance was the secondary focus. METHODS: Twenty-eight patients with arthroscopic Bankart repair using knotless PLLA anchors were prospectively followed and analyzed using a clinical scoring system (3, 6, 15 and 32 months). The T2-weighted OR and T1 weighted DHC were assessed using specific magnetic resonance imaging grading protocols (15 and 32 months). RESULTS: Longitudinal assessments revealed successive clinical status improvements over time (32 months: Rowe 95.7 +/- 3.8; Walch-Duplay 93.8 +/- 6.6; Constant 93.9 +/- 4.5; ASES 93.8 +/- 6.9; DASH 28.6 +/ 7.2; NAS(pain) 1.1 +/- 1.3; NAS(function) 1.3 +/- 1.4). The initial OR level regressed over the 15-32 month period while the DHC showed significant drill hole reductions (P < 0.05). The inferior glenoid revealed a significantly increased bio-degradation capacity (P < 0.05) with drill hole enlargements in 14.3%. Neither the OR nor the drill hole enlargements influenced the clinical status. In no case were clinical or radiologic signs for a foreign body reaction. CONCLUSION: Knotless bio-anchors provide secure glenoidal fixation for Bankart repair without any specific clinical or MR evidence of an inflammatory response. The clinical status remained unaffected by the bio-degradation process. LEVEL OF EVIDENCE: IV. PMID- 22045196 TI - Concussion and the adolescent athlete. AB - Traumatic brain injury (TBI) is a complex and debilitating neurological injury that places a significant financial and emotional burden on both families and medical providers. Accumulating evidence suggests that mild TBI or concussion remains grossly underdiagnosed, as compared with more severe TBI, due to a poor understanding of the clinical signs and symptoms involved with a head injury. Notably, pediatric head injury may be associated with the subsequent development of serious, long-term neurological consequences, emphasizing the need for improved diagnosis and acute medical intervention. The purpose of this minireview is to summarize the association between participation in youth athletics and the occurrence of concussions, a primary source of mild TBI in the adolescent population, with the goal of increasing awareness within the nursing profession for this clinically important yet underdiagnosed form of brain injury. PMID- 22045197 TI - Relative contribution of tissue oedema and the presence of an A2 pulley to resistance to flexor tendon movement: an in vitro and in vivo study. AB - Increases in the resistance to tendon during movement may lead to rupture or gapping of the repaired tendon. The relative contribution of these factors-tissue oedema, tendon oedema, and the intact A2 pulley-to resistance to tendon gliding is unclear. In in vitro chicken models, we created oedema in subcutaneous tissue or tendon. The work of digital flexion (WOF) increased significantly after creation of oedema in those tissues. WOF decreased significantly after division of the A2 pulley. Preservation of the integrity of the A2 pulley significantly increased WOF at post-operative weeks 1 and 2 in the in vivo chicken model; increases in WOF were greater than those due to the presence of oedematous subcutaneous tissue. Pulley division at the time of surgery reduced WOF more drastically than the removal of volar subcutaneous tissue. Presence of an intact A2 pulley adds greater resistance to the movement of the repaired flexor tendon than volar oedematous subcutaneous tissue. PMID- 22045198 TI - Long-term results of major upper extremity replantations. AB - We analyzed the long-term functional outcome in patients with major upper extremity replantations. Two patients had amputations proximal to the elbow joint, two had elbow disarticulations and five patients had amputations at the forearm. The mean age was 24 and the mean follow-up time was 18 years. Six patients have undergone secondary operations. The mean grip strength was restored to 34% of the contralateral extremity. Protective sensation was restored in all patients. According to Chen's functional recovery scale, five patients had excellent, two had good, and two had fair results. Grip strength, two-point discrimination, ranges of motion and Chen's scale did not improve after 5 years. However, Semmes-Weinstein monofilament testing and cold intolerance continued to improve up to 10 and 12 years, respectively. Replantation of an upper extremity proximal to the wrist joint satisfactorily restored the upper extremity function. PMID- 22045199 TI - Treatment of an osteoporotic vertebral compression fracture with the StaXx FX system resulting in intrathoracic wafers: a serious complication. AB - PURPOSE: To report a serious complication of the StaXx FX system used to stabilize an osteoporotic vertebral fracture. CASE REPORT: A 76-year-old woman presented with a painful vertebral fracture. Treatment by means of a PEEK wafer kyphoplasty was complicated by malposition of the wafers. The patient recovered fully after removal of the wafers by means of a thoracotomy. CONCLUSIONS: New treatment modalities have their own pitfalls and possible complications, as demonstrated in this case report. Caution regarding implementation of new treatment modalities should be practiced. PMID- 22045200 TI - Patients with adolescent idiopathic scoliosis of Lenke type-1 curve exhibit specific pedicle width pattern. AB - INTRODUCTION: Study aim was to find out if patients with Lenke type 1 curve exhibit smaller pedicles and specific pedicle width pattern compared with individuals with no scoliosis. MATERIALS AND METHODS: 4,828 pedicle width measurements (T1-L5) in 61 consecutive patients with adolescent idiopathic scoliosis of Lenke type 1 curve, 61 control subjects, and 20 patients with Lenke type 5 curve, were retrospectively performed by an experienced neuroradiologist. RESULTS: Among patients with Lenke type 1 curve, the differences between the width of right and left upper thoracic pedicles were statistically significant; smallest at right T4 (2.6 mm). At scoliotic apex, the pedicles on the concave (left) side were significantly smaller than those on the convex (right) side; smallest at left T7 (3.2 mm). Among patients with Lenke type 1 curve, 97% had pedicle width <4 mm. CONCLUSIONS: Our study showed that patients with Lenke type 1 curve exhibit smaller pedicles and asymmetric pedicle width compared with control subjects. PMID- 22045201 TI - A case of acute renal failure after exercise with renal hypouricemia demonstrated compound heterozygous mutations of uric acid transporter 1. AB - Familial renal hypouricemia is a hereditary disease characterized by extraordinary high renal uric acid (UA) clearance and is associated with acute renal failure (ARF). A 17-year-old Japanese male developed ARF after anerobic exercise. Renal function improved completely after approximately 2 weeks of hydration treatment. After remission, hypouricemia became evident (1.0 mg/dL) from the initial level of UA (4.8 mg/dL) and fractional excretion of uric acid (FEUA) was >50%. His parents showed normal levels of UA and FEUA. Polymerase chain reaction of a urate anion exchanger known to regulate UA level [SLC22A12 gene: UA transporter 1 (URAT1)] demonstrated compound heterozygous mutations (Q297X and R90H). Thus, we describe a Japanese male with hypouricemia complicated by anerobic exercise-induced ARF, with definite demonstration of a genetic abnormality in the responsible gene, URAT1. PMID- 22045202 TI - Magnetic behavior in UFe2Zn20 and URu2Zn20 single crystals. AB - The magnetic, electrical transport and thermodynamic properties of the compounds UFe2Zn20 and URu2Zn20 were studied on single-crystalline specimens over wide ranges of temperature and magnetic field. The results indicate that the two ternaries are paramagnetic moderately enhanced heavy fermion systems. Their physical behavior is governed predominantly by the hybridization of uranium 5f orbitals with electronic states of ligands, which brings about considerable delocalization of the 5f states. PMID- 22045203 TI - The herbal medicine Inchinko-to reduces hepatic fibrosis in cholestatic rats. AB - PURPOSE: Several studies have reported the herbal medicine Inchinko-to (ICKT) to have an antifibrotic effect which thus leads to an improvement of hepatic injury. However, there are still few reports of its use in the treatment of cholestatic liver disorder. The aim of this study was to clarify whether the administration of ICKT will ameliorate hepatic fibrosis and injury in cholestatic rats. MATERIALS AND METHODS: We performed bile duct ligation on 7-week-old male cholestatic Wistar rats and assigned them to one of three groups according to the method of treatment: (1) the SHAM group, (2) the NT-group (non-treatment group), and (3) the T-group (treatment-group). Rats in the T-group were orally administered ICKT (TJ-135) at a dose of 1 g/kg/day and were killed on the 17th postoperative day. We subsequently investigated the levels of fibrosis and various clinical markers through measurement of the following: serum levels of AST and ALT; tissue transforming growth factor-beta 1 (TGF-beta1); tissue inhibitor metalloprotease-1 mRNA (TIMP-1 mRNA) through real-time PCR analysis; and Azan staining and immunohistochemical staining of alfa-smooth muscle actin (alfa-SMA) to evaluate the degree of fibrosis. RESULTS: The levels of serum AST, serum ALT, and TGF-bata1 in the T-Group were significantly lower than those in the NT-Group. In addition, staining of Azan and alfa-SMA in the T-Group was significantly lower than those in the NT-Group. CONCLUSION: ICKT may help reduce hepatic fibrosis and injury by controlling stellate cell activation. PMID- 22045204 TI - Regulating the levels of key factors in cell cycle and DNA repair: new pathways revealed by lamins. AB - Spatial and temporal organization of the genome represents an additional step in the regulation of nuclear functions. The nuclear lamina, a polymeric meshwork formed by lamins (A/C and B type) and lamin-associated proteins, plays a key role in the maintenance of genome localization, structure and function. Specifically, mutations in the LMNA gene encoding lamins A/C or changes in its expression, either upregulation or silencing, are associated with defects in DNA replication, transcription and repair, as well as alterations in epigenetic modifications of chromatin. These data, together with the fact that defects in A-type lamins are associated with a whole variety of degenerative disorders, premature aging syndromes and cancer, support the notion that these proteins operate as caretakers of the genome. However, our understanding of their functions is limited due to the lack of well-defined mechanisms behind the genomic instability observed in lamin-related diseases. Here, we summarize our recent discovery of new pathways that are affected by the loss of A-type lamins. In particular, we found that A-type lamins control transcription and degradation of proteins with key roles in cell cycle regulation and DNA double-strand breaks (DSBs) repair by non-homologous end-joining (NHEJ) and homologous-recombination (HR). Importantly, the proteins regulated by A-type lamins--Rb family members, 53BP1, BRCA1 and RAD51--exert tumor suppressor functions, with their loss being associated with cancer susceptibility. Moreover, our studies revealed novel pathways that contribute to genomic instability and that can be activated in disease states independent of the status of A-type lamins. PMID- 22045205 TI - IBD: Risk of colorectal cancer in African Americans with ulcerative colitis. PMID- 22045214 TI - Probiotics: Probiotics and diarrhea in children. PMID- 22045215 TI - Pediatrics: Liver transplantation in very small recipients. PMID- 22045216 TI - Comparative photophysical properties between bicyclo[2.2.2]octadiene (BCOD)- and benzo-fused free-base triphyrins (2.1.1). AB - We have investigated the photophysical properties of two types of triphyrins with focus on the fused-moiety effects by performing various spectroscopic measurements and theoretical calculations. PMID- 22045218 TI - Rapid one-step assays for on-site monitoring of mouse and rat urinary allergens. AB - Allergy to rodent proteins is common among laboratory animal workers. Sensitive methods to measure exposure to these allergens have been developed. These assays are, however, expensive, time-consuming, and require a laboratory facility and methodological expertise. A simple method to screen for allergen spread, or to test whether hygiene standards are maintained, would be useful. Lateral flow immunoassays (LFIAs) are especially suited for field settings; the tests are simple and results are visible within minutes. LFIAs were developed for detection of the rodent urinary allergens Mus m 1 and Rat n 1. Pilot studies were performed in animal facilities in three countries using both extracts from airborne dust samples and samples collected by wiping surfaces. For comparison and determination of sensitivity, the concentrations of rodent urinary allergens in the samples were also measured using enzyme immunoassays (EIAs). The LFIAs for rat and mouse urinary allergens had a detection limit of 31 pg allergen per mL in a buffer system with purified allergen standards. Results of environmental dust extracts tested in LFIAs correlated well with levels obtained using EIAs. Spread of rodent allergens, or non-adherence to hygiene around laboratory animal facilities, may aggravate rodent allergy. Using a simple, sensitive one-step assay, allergens can be detected to prevent allergen exposure. The results reveal that the rapid assays are suited for on-site demonstration of exposure to rodent allergens, and thus, useful in occupational hygiene practice. PMID- 22045217 TI - A contemporary review of seafood allergy. AB - Seafood is common item in the world diet; Asian countries have the highest rates of fish consumption in the world, which is higher than world average. Several studies have been conducted on the epidemiology and clinical characteristics of seafood allergy in different countries, and some of the fish and seafood allergens unique to those regions have been characterized. Review on published data showed that seafood allergy is very ubiquitous in some regions of the world. Fish and shellfish are the most common seafood that cause adverse allergic reactions among nations; the symptoms ranged from oral allergy syndromes to urticaria and anaphylaxis. The major identified allergens are parvalbumin in fish and tropomyosin in shellfish. Nevertheless, such studies are lacking from some regions with high fish and seafood consumption. Furthermore, the published data are mostly from small groups of populations, which large-scale epidemiological studies need to be performed. PMID- 22045219 TI - Clinical appraisal of chronic traumatic encephalopathy: current perspectives and future directions. AB - PURPOSE OF REVIEW: There are currently no consensus-based clinical diagnostic criteria for chronic traumatic encephalopathy (CTE). This review provides an update on recent literature pertaining to clinically relevant procedures that- presently or in the future--may be useful for the in-vivo detection, characterization, and/or prediction of CTE. RECENT FINDINGS: Preliminary evidence about the clinical manifestations of CTE has been accumulating via post-mortem medical record review and interviews of friends or family members of individuals with neuropathologically documented CTE. This evidence suggests that CTE is manifested clinically by changes in cognition (especially memory and executive functioning, with dementia later in the disease course), mood (especially, depression, apathy, and suicidality), personality and behavior (especially poor impulse control and behavioral disinhibition), and movement (including parkinsonism and signs of motor neuron disease). At the present time, evidence regarding CTE has not been confirmed in a prospective study of a cohort at risk for CTE. SUMMARY: On the basis of recent research in the fields of dementia and traumatic brain injury, several in-vivo procedures (including neurological examination, neuropsychological assessment, neuroimaging techniques, and blood and cerebrospinal fluid biomarkers) each have the potential to contribute unique information about the manifestations of CTE, including clinical and preclinical stages. More research is needed to develop a set of consensus diagnostic criteria that provide a reliable and valid indicator of neuropathologically verified CTE. Until such criteria are developed, the clinical assessment of CTE should be informed by modern research that is of relevance to traumatic brain injury and neurodegenerative diseases. PMID- 22045220 TI - Advances in ultra-high field MRI for the clinical management of patients with brain tumors. AB - PURPOSE OF REVIEW: The last 5 years have seen the number of ultra-high field (UHF; 7 T and beyond) MRI scanners nearly double. Benefits include improved specificity, better sensitivity for signal-starved compounds, and the ability to detect, quantify, and monitor tumor activity and treatment effects. This is especially important in the current climate in which new treatments alter established markers of tumor and the surrounding environment, confounding traditional response criteria. RECENT FINDINGS: Intra-tumoral heterogeneity and dramatic improvement in spatial localization have been observed with 7 and 8 T high-resolution T2-weighted and T2*-weighted imaging. This depiction of lesions that were not readily detected at lower field improved the classification of glioma. Sub-millimeter visualization of microvasculature has facilitated the detection of microbleeds associated with long-term effects of radiation. New metabolic markers seen at UHF may also assist in distinguishing tumor progression from treatment effect. SUMMARY: Although progress has been limited by technical challenges, initial experience has demonstrated the promise of 7-T MRI in advancing existing paradigms for diagnosing, monitoring, and managing patients with brain tumors. The success of these systems will depend upon what new information can be gained by UHF, rather than simply improving the quality of the current lower field standard. PMID- 22045221 TI - Extracellular superoxide dismutase overexpression can reverse the course of hypoxia-induced pulmonary hypertension. AB - Hypoxia leads to free radical production, which has a pivotal role in the pathophysiology of pulmonary hypertension (PH). We hypothesized that treatment with extracellular superoxide dismutase (EC-SOD) could ameliorate the development of PH induced by hypoxia. In vitro studies using pulmonary microvascular endothelial cells showed that cells transfected with EC-SOD had significantly less accumulation of xanthine oxidase and reactive oxygen species than nontransfected cells after hypoxia exposure for 24 h. To study the prophylactic role of EC-SOD, adult male wild-type (WT) and transgenic (TG) mice, with lung specific overexpression of human EC-SOD (hEC-SOD), were exposed to fraction of inspired oxygen (FiO(2)) 10% for 10 d. After exposure, right ventricular systolic pressure (RVSP), right ventricular mass (RV/S + LV), pulmonary vascular wall thickness (PVWT) and pulmonary artery contraction/relaxation were assessed. TG mice were protected against PH compared with WT mice with significantly lower RVSP (23.9 +/- 1.24 versus 47.2 +/- 3.4), RV/S + LV (0.287 +/- 0.015 versus 0.335 +/- 0.022) and vascular remodeling, indicated by PVWT (14.324 +/- 1.107 versus 18.885 +/- 1.529). Functional studies using pulmonary arteries isolated from mice indicated that EC-SOD prevents hypoxia-mediated attenuation of nitric oxide induced relaxation. Therapeutic potential was assessed by exposing WT mice to FiO(2) 10% for 10 d. Half of the group was transfected with plasmid containing cDNA encoding human EC-SOD. The remaining animals were transfected with empty vector. Both groups were exposed to FiO(2) 10% for a further 10 d. Transfected mice had significantly reduced RVSP (18.97 +/- 1.12 versus 41.3 +/- 1.5), RV/S + LV (0.293 +/- 0.012 versus 0.372 +/- 0.014) and PVWT (12.51 +/- 0.72 versus 18.98 +/- 1.24). On the basis of these findings, we concluded that overexpression of EC SOD prevents the development of PH and ameliorates established PH. PMID- 22045222 TI - The indirect costs of cancer-related absenteeism in the workplace in Poland. AB - OBJECTIVES: The aim of this study was to evaluate cancer-related absenteeism costs in Poland. METHODS: Data on sickness absences and disability were retrieved from the Department of Statistics of the Social Insurance Institution. The cost of lost productivity owing to premature death was estimated from data retrieved from the Polish National Cancer Registry. Absenteeism costs were estimated on the basis of the measure of gross value added per employee. RESULTS: The costs of lost productivity owing to sick leave, disability, and premature death were estimated to be 1.572 billion EUR, 0.504 billion EUR, and 0.535 billion EUR, respectively, in 2009. CONCLUSIONS: The indirect costs of lost productivity owing to cancer-related sick leave, disability, and premature death have a substantial effect on the Polish economy. In 2009, they accounted for more than 0.8% of GDP. PMID- 22045223 TI - Fibre intake in relation to serum total cholesterol levels and CHD risk: a comparison of dietary assessment methods. AB - BACKGROUND/OBJECTIVES: Prospective diet diaries may be more accurate than retrospective food frequency questionnaires (FFQ). The objective of this study was to compare FFQ and 7-day diet diary (7DD) measurements of fibre intake with the incidence of coronary heart disease (CHD). SUBJECTS/METHODS: We compared 7DD and FFQ fibre intake in a nested case-control study in a population of 25639 men and women aged 40-79 years, surveyed in 1993-97 and followed up until 2007. Among 2151 CHD cases and 5354 controls, FFQ and 7DD fibre intake (6 g/day) was examined in relation to serum total cholesterol and CHD using linear and logistic regression adjusted for age and additionally for body mass index, physical activity, smoking status, family history of CHD, social class, diabetes, alcohol, energy, saturated fat and use of lipid lowering medication, antihypertensive medication or aspirin. RESULTS: Age-adjusted serum total cholesterol was inversely associated with 7DD fibre among men and women, but with FFQ fibre among men only. In the multivariate analysis, associations with 7DD fibre were attenuated among men (regression coefficient -0.036 mmol/l, s.e. 0.021, P-value 0.087) and women (regression coefficient -0.069 mmol/l, s.e. 0.036, P-value 0.053), and were non-significant for FFQ fibre. Among men, age-adjusted CHD risk was inversely associated with 7DD fibre (odds ratio (OR) 0.84, 95% confidence interval (CI) 0.79-0.90), but not with FFQ fibre (OR 0.96, 95% CI 0.90-1.12). Among women, age-adjusted CHD risk was inversely associated with 7DD fibre (OR 0.83, 95% CI 0.75-0.93), and had a weaker inverse borderline-significant association with FFQ fibre (OR 0.93, 95% CI 0.87-1.01). Multivariate models yielded similar results. CONCLUSIONS: Inconsistencies in diet-CHD relationships in population studies may be associated with the use of different dietary assessment methods. PMID- 22045224 TI - The potential impact of nutrient profiles on dairy-related energy and nutrient intake in German children and adolescents. AB - BACKGROUND/OBJECTIVES: To evaluate the potential impact of nutrient profiling based dairy product choices on energy and nutrient intake in German children and adolescents. SUBJECTS/METHODS: Consumption data were obtained from product specific dietary records in the DONALD Study (Dortmund Nutritional and Anthropometric Longitudinally Designed Study). We compared actual intake data with intake data that were calculated based on the assumption that participants exclusively consumed products that met the criteria of selected nutrient profiling models. RESULTS: For most profiling models, the percentage of compliant products was unrelated to the percentage of the participants' dairy consumption rated eligible. The participants' intake of energy, saturated fatty acids (SAFA), sodium, calcium and vitamin D would be reduced significantly (P<0.0001) if only qualifying products were consumed. The impact on the participants' nutrient intake levels was not directly related to the impact on the product's nutrient content levels. Lower fat consumption was correlated with reduced vitamin D intake, and the models' disqualification of (semi-) hard cheeses had a negative impact on the calcium intake. CONCLUSIONS: The evaluation of product-specific intake data was critical to understand the potential impact of any profiling scheme on nutrient intake. Selecting dairy products based on nutrient profiling could help reduce the intake of less-desirable nutrients, such as SAFA and sodium. However, models that are too restrictive might negatively impact calcium and vitamin D intake. Ultimately, the effectiveness of nutrient profiling models will be determined by the fact whether or not complying foods are consumed. PMID- 22045225 TI - Trends in food availability in Switzerland, 1961-2007. AB - Trends in food availability in Switzerland were assessed using the Food and Agricultural Organization food balance sheets for the period 1961-2007. A relatively stable trend in the daily caloric supply was found: 3545 kcal/day in 1961 and 3465 kcal/day in 2007. Calories associated with carbohydrates decreased (slope+/-s.e.: -1.1+/-0.2 kcal/day/year), namely regarding cereals (-2.9+/-0.6 kcal/day/year) and fruit (-1.5+/-0.1 kcal/day/year), while the availability of sugars increased (1.2+/-0.5 kcal/day/year). In 1961, protein, fat, carbohydrates and alcohol represented 10.6, 33.5, 50.0 and 5.9% of total caloric supply, respectively; in 2007, the values were 10.8, 40.3, 43.7 and 5.2%. In 1961, palm, groundnut and sunflowerseed oil represented 3.4, 30.7 and 5.3% of total vegetable oils, respectively; in 2007, the values were 10.4, 3.7 and 31.6%. We conclude that between 1961 and 2007 total caloric availability remained relatively stable in Switzerland; the health effects of the increased and differing fat availability should be evaluated. PMID- 22045226 TI - Non-contact assessment of waist circumference: will tape measurements become progressively obsolete? AB - Waist circumference (WC) is a key variable to assess in health management as it is a proxy of abdominal fat mass and a surrogate marker of cardiometabolic disease risk, including the metabolic syndrome. Recently, a portable non-contact device calculating WC (ViScan) has been developed, which hence allows the tracking of WC independently of the inter-investigators error. We compared WC values obtained with this device with WC measured by simple non-stretchable tape in 74 adults of varying body mass indices (range 17-39 kg/m(2)). The correlation between the two methods was very high (r=0.97, P<0.0001) and the reproducibility (precision) assessed with a rigid phantom was excellent (<1 cm, coefficient of variability<1%). The instrument constitutes a potentially valuable tool for longitudinal surveys and comparative international studies, which require simple but precise measurements of WC in order to track the effect of subtle changes on various health outcomes. PMID- 22045227 TI - Elevated survivin is associated with a poor response to chemotherapy and reduced survival in lung cancer with malignant pleural effusions. AB - Survivin has been shown to inhibit apoptosis, enhance proliferation and promote angiogenesis. This study aimed to identify diagnostic value of survivin protein in malignant pleural effusion (MPE) and to investigate the prediction of response to chemotherapy and the prognostic role on pleural survivin in lung cancer patients with MPE. Pleural effusion samples were collected from 67 patients with MPE (58 lung cancers; 9 extrathoracic tumors), and from 68 patients with benign conditions (31 with pneumonia; 37 with tuberculosis). Concentrations of pleural fluid survivin, Cyfra 21-1, and carcinoembryonic antigen (CEA) were measured by enzyme-linked immunosorbent assay. The expression profile of survivin in pleural fluid, and its association with survival, were investigated. Survivin levels were significantly elevated in patients with MPE, especially primary lung cancer than in those of benign origin. Survivin, Cyfra 21-1, and CEA varied in diagnostic accuracy for differentiating MPE from benign pleural effusion by 67.5, 68.3, and 93.4%, respectively. Lung cancer patients with MPE who were positive for survivin expression were more refractory to chemotherapy (P = 0.003). Positive for survivin expression was correlated with a reduced overall survival in univariate (P = 0.0001) and multivariate (P = 0.004) analyses. Using the appropriate cut-off points, CEA in pleural fluid has a higher accuracy than other tumor markers, and that survivin has a low diagnostic accuracy for differentiating MPE from benign pleural effusion. Our findings suggest that positive survivin expression may be used as a predictor of a poor response to chemotherapy and shorter survival in lung cancer patients with MPE. PMID- 22045228 TI - Wobble base-pairing slows in vivo translation elongation in metazoans. AB - In the universal genetic code, most amino acids can be encoded by multiple trinucleotide codons, and the choice among available codons can influence position-specific translation elongation rates. By using sequence-based ribosome profiling, we obtained transcriptome-wide profiles of in vivo ribosome occupancy as a function of codon identity in Caenorhabditis elegans and human cells. Particularly striking in these profiles was a universal trend of higher ribosome occupancy for codons translated via G:U wobble base-pairing compared with synonymous codons that pair with the same tRNA family using G:C base-pairing. These data support a model in which ribosomal translocation is slowed at wobble codon positions. PMID- 22045229 TI - Laparoscopic total gastrectomy for multiple sporadic gastric gastrointestinal stromal tumors: report of a case. AB - A 64-year-old man was admitted to our hospital with hematemesis. Emergency upper gastrointestinal endoscopy revealed bleeding from a submucosal tumor (SMT) in the antrum of the stomach, with two other SMTs at different sites. Based on his family history, we diagnosed familial multiple gastric gastrointestinal stromal tumors (GISTs) and performed laparoscopic total gastrectomy. Three distinct tumors were found: one in the fornix, one in the lesser curvature of the angle, and one in the antrum of the stomach. Microscopic examination of the resected specimens revealed different cytomorphologies, of the spindle and epithelioid type, as well as immunophenotypes in the tumors. Mutation analysis revealed different sites of mutation in c-kit and PDGFRA. No mutation was detected in the normal tissue of the stomach. These findings confirmed a diagnosis of multiple sporadic gastric GISTs. Thus, investigating germline mutation might assist in the preoperative diagnosis of multiple gastric GISTs. PMID- 22045230 TI - Successful resection of a massive mediastinal liposarcoma that rapidly extended into the entire left thoracic cavity: report of a case. AB - Primary mediastinal liposarcomas are rare malignancies, comprising fewer than 1% of all mediastinal tumors. We herein report a radical resection of a massive liposarcoma arising from the anterior mediastinum. A 63-year-old male patient presented with a 4-week history of dyspnea that had worsened over the previous several days. The patient had also experienced hoarseness for 2 weeks. Chest X ray and computed tomography revealed a huge tumor occupying the entire left thoracic cavity. Anesthesia was induced when the patient was in the left semilateral position. The patient was moved into the right lateral position after initially stabilizing anesthesia with separate lung ventilation. The fourth rib was initially resected for thoracotomy, but there was no clearance between the tumor and the adjacent mediastinal structures, and two more ribs were therefore removed. The tumor had not invaded the other structures such as the chest wall, lung, or mediastinum. To reduce the tumor blood flow, the left internal mammary artery was ligated before the tumor was resected en bloc. The tumor was diagnosed as a liposarcoma arising from the thymus. The patient remains alive with no evidence of disease recurrence at 22 months after the operation. PMID- 22045231 TI - Digital evaluation of the muscle functions of the lower extremities among inguinal hernia patients treated using three different surgical techniques: a prospective randomized study. AB - PURPOSE: An inguinal hernia is a common pathology that can be treated using several different surgical procedures. Although there have been many studies comparing the clinical results of these techniques, there has so far been no digital analysis of the alterations developing secondary to pain with regard to the muscle functions of the lower extremities. This prospective randomized trial was designed to compare this aspect for subjects treated using the laparoscopic techniques and those treated using the conventional method. METHODS: A total of 75 patients, 25 of whom who had undergone hernia repair using the total extraperitoneal technique, 25 of whom who had undergone repair using the transabdominal preperitoneal technique, and 25 who had undergone repair using the Prolene mesh graft technique, were evaluated preoperatively and on the third postoperative day by isometric and isokinetic measurements, the visual analog score (VAS), the necessity of postoperative analgesia, complications, and the time that had elapsed before returning to work, and these results were recorded. RESULTS: Hernia repair using the conventional method led to an average of 3 times more muscle function loss compared with the laparoscopic techniques, and this difference was shown to be statistically significant. The VAS, postoperative complications, and time elapsed before returning to work were lower for laparoscopic surgeries and also were compatible with the findings described in the previous literature. CONCLUSIONS: Use of a digital environment with numerical parameters and measurements recorded using a dynamometer demonstrated that in the early postoperative period and on the third postoperative day, open surgery causes more functional loss in the lower extremities than laparoscopic methods. Therefore, surgeons should use laparoscopic methods whenever possible to reduce both pain and loss of muscle function. PMID- 22045232 TI - Spontaneous regression of multiple pulmonary recurrences of hepatocellular carcinoma after hepatectomy: report of a case. AB - Spontaneous regression of hepatocellular carcinoma (HCC) is an extremely rare phenomenon. We herein report the case of a 73-year-old man who showed the spontaneous regression of multiple pulmonary recurrences of HCC that had occurred after hepatectomy. The patient was undergoing dialysis due to diabetic renal failure when ultrasonography revealed a liver tumor (diameter ~ 10 cm). A preoperative diagnosis of HCC with hepatic vein thrombosis was made. The liver function was well preserved and then the right hepatic vein area was resected. Two months after hepatectomy the alpha-fetoprotein level increased, and multiple lung nodules were observed on follow-up computed tomography. A diagnosis of multiple lung metastases was made, but no therapy was started because of the patient's renal failure. Five months after hepatectomy the alpha-fetoprotein level normalized, and the metastases regressed completely. The patient is now doing well without any recurrence at 13 months after the surgery. The associated literature on spontaneous HCC regression is also reviewed. PMID- 22045233 TI - Surgical management of small bowel metastases from primary carcinoma of the lung. AB - PURPOSE: To investigate the treatment and outcomes in a series of seven cases of small bowel metastases from lung cancer. METHODS: A total of 4114 patients with lung cancer were referred to this institution from 1995 to 2005. Seven (0.17%) developed symptomatic small bowel metastasis and were treated surgically. The clinical, radiological, and pathological records were reviewed. RESULTS: Small bowel metastases were diagnosed from 0 to 31 months (mean 11.5 months) after the diagnosis of lung cancer. The clinical symptoms at presentation were acute peritonitis in two patients and abdominal pain in five. Small bowel metastasis was suspected on abdominal X-ray in three cases, computed tomography in two, small bowel radiography in one, and endogastroduodenoscopy in one. All patients underwent surgery and there were no perioperative deaths. Intestinal resection was performed in five cases and a bypass in two. A small bowel metastasis was found in the ileum in four patients. The mean survival period was 7.7 months after surgery. One patient lived for 22 months after bowel resection. Oral intake was possible 1 month after surgery in six cases. CONCLUSION: Surgical management should be considered as palliative treatment in patients with a bowel obstruction or peritonitis caused by primary lung cancer. PMID- 22045234 TI - Successful closure of an open-window thoracostomy wound by negative-pressure wound therapy: report of a case. AB - Negative-pressure wound therapy is a newly developed, noninvasive technique to manage a wide variety of wounds. This novel therapy was successfully used to heal the wound after open-window thoracostomy without surgical closure. A 46-year-old woman was admitted to hospital because of a painful mass on the right side of her chest. Radiological findings revealed an abscess on the right chest wall that had ruptured into the right lung and caused empyema. Antibiotic therapy did not yield sufficient improvement. Open-window thoracostomy was performed to achieve a sterile pleural space, and negative-pressure wound therapy was then applied. The pleural space was reduced, and the patient was discharged home with self administered wound care. The wound healed completely in 5 months without any need for surgical closure. PMID- 22045235 TI - Will (or can) people pay for headache care in a poor country? AB - We asked whether attempts to introduce headache services in poor countries would be futile on grounds of cost and unsustainability. Using data from a population based survey in the Republic of Georgia, an exemplary poor country with limited health care, and against the background of headache-attributed burden, we report on willingness to pay (WTP) for effective headache treatment. Consecutive households were visited in areas of Tbilisi (urban) and Kakheti (rural), together representative of Georgian habitation. Biologically unrelated adults were interviewed by medical residents using a structured ICHD-II-based diagnostic questionnaire, the MIDAS questionnaire and SF-36. The bidding-game method was employed to assess WTP. Of 1,145 respondents, 50.0% had episodic headache (migraine and/or tension-type headache) and 7.6% had headache on >=15 days/month, which was not further diagnosed. MIDAS scores were higher in people with headache on >=15 days/month (mean 11.2) than in those with episodic headache (mean 7.0; P = 0.004). People with headache had worse scores in all SF-36 sub-scales than those without, but no differences were found between headache types. Almost all (93%) respondents with headache reported WTP averaging USD 8 per month for effective headache treatment. WTP did not correlate with headache type or frequency, or with MIDAS or SF-36 scores. Headache is common and headache attributed burden is high in Georgia, with a profound impact on HRQoL. Even those less affected indicated WTP for effective treatment, if it were available, that would on average cover costs, which locally are low. Headache services in a poor country are potentially sustainable. PMID- 22045236 TI - Structural changes in the hippocampus and amygdala at first episode of psychosis. AB - Hippocampus and amygdala changes have been implicated in the pathophysiology and symptomatology of both schizophrenia (SCZ) and bipolar disorder (BD). However relationships between illness course, neuropathological changes and variations in symptomatology remain unclear. This investigation examined the associations between hippocampus and amygdala volumes and symptom dimensions in schizophrenia and bipolar disorder patients after their first episode of psychosis. Symptom severity was associated with decreases in hippocampus/amygdala complex volume across groups. In keeping with previous work bilateral hippocampus and amygdala volume reductions were also identified in the SCZ patients while in BD patients only evidence of amygdala inflation reached significance. The study concludes that there appear to be important relationships between volume changes in the hippocampus and amygdala and dimensions and severity of symptomatology in psychosis. Structural alterations are apparent in both SCZ and BD after first episode of psychosis but present differently in each illness and are more severe in SCZ. PMID- 22045237 TI - Acute kidney injury: Severity of illness scoring systems in acute kidney injury. PMID- 22045238 TI - Dialysis: Initiation of dialysis at higher levels of eGFR: what are the implications for patients? PMID- 22045239 TI - Clinical usefulness of novel prognostic biomarkers in patients on hemodialysis. AB - Prognosis, risk stratification and monitoring the effects of treatment are fundamental elements in the decision-making process when implementing prevention strategies for chronic kidney disease. The use of biomarkers is increasingly proposed as a method to refine risk stratification and guide therapy. In this Review, we present basic concepts regarding the validation of biomarkers and highlight difficulties inherent to the identification of useful new biomarkers in patients on hemodialysis. We focus on prognostic biomarkers that have been consistently linked to survival in this group of patients. To date, no biomarker has had sufficient full-scale testing to qualify as a useful addition to standard prognostic factors or to guide the prescription of specific treatments in this population. Furthermore, little information exists on the relative strength of various biomarkers for their prediction of mortality. A multimarker approach might refine prognosis in patients on hemodialysis, but this concept needs to be properly evaluated in large longitudinal studies and clinical trials. The potential of proteomics for the identification and study of new biomarkers in the pathophysiology of cardiovascular disease in patients with end-stage renal disease is also discussed. PMID- 22045240 TI - Effluent volume and dialysis dose in CRRT: time for reappraisal. AB - The results of several studies assessing dialysis dose have dampened the enthusiasm of clinicians for considering dialysis dose as a modifiable factor influencing outcomes in patients with acute kidney injury. Powerful evidence from two large, multicenter trials indicates that increasing the dialysis dose, measured as hourly effluent volume, has no benefit in continuous renal replacement therapy (CRRT). However, some important operational characteristics that affect delivered dose were not evaluated. Effluent volume does not correspond to the actual delivered dose, as a decline in filter efficacy reduces solute removal during therapy. We believe that providing accurate parameters of delivered dose could improve the delivery of a prescribed dose and refine the assessment of the effect of dose on outcomes in critically ill patients treated with CRRT. PMID- 22045241 TI - Transplantation: Induction of immune tolerance in kidney transplant recipients. PMID- 22045242 TI - The podocyte as a target for therapies--new and old. AB - Injury to the podocyte results in proteinuria and often leads to progressive kidney disease. As podocytes have limited ability to repair and/or regenerate, the extent of podocyte injury is a major prognostic determinant in diabetic nephropathy and other common causes of end-stage renal disease. Therapies aimed at preventing or limiting podocyte injury and/or at promoting podocyte repair or regeneration therefore have major potential clinical and economic benefits. Many current therapies--including glucocorticosteroids and calcineurin antagonists- have potent effects on podocytes. The nonspecific natures of these agents lead to undesirable systemic adverse effects: an agent with a more specific focus on podocytes would cause less treatment-associated morbidity. Recent years have seen dramatic advances in our understanding of podocyte biology and in particular regulation of its actin cytoskeleton, the major determinant of the complex architecture on which these cells depend for their function. This advance has allowed the identification of potential therapeutic targets and the next few years should see the development and testing of specific therapies aimed at the podocyte. Thus we are about to move from a situation where some of our 'blunderbuss' older therapies fortuitously happened to have beneficial effects on podocytes to a new era where advances in biological knowledge about a key cell type in the kidney will allow targeted drug design. As well as being intellectually more satisfying, every reason exists to believe that patients of the future will benefit and that the scourge of progressive kidney disease will be more effectively tackled. PMID- 22045244 TI - Persistent photoinduced magnetization in the coexisting spin-glass and ferromagnetic phases of Pr0.9Ca0.1MnO3 thin film. AB - The persistent photoinduced magnetization (PPM) in the low bandwidth material Pr(1-x)Ca(x)MnO3 at the low hole doping level of x = 0.1 is reported. Upon zero field cooling under photoexcitation, significant improvement of the ferromagnetic (FM) ordering was observed in the low temperature spin-glass phase. However, upon field cooling, the FM ordering was found to be suppressed due to weakening of the double-exchange interaction. High kinetic energy x-ray photoelectron spectroscopy measurements indicated a slight increase in the Mn3+ peak under photoexcitation which clarifies the weakening of the FM interaction. The fast relaxation of the PPM is discussed in view of localization of spin polarons in sites of magnetic disorders and the results are compared with previous reports of PPM in intermediate bandwidth Pr0.9Ca0.1MnO3 samples. PMID- 22045243 TI - The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. AB - Renal failure remains a principal cause of morbidity for patients with multiple myeloma. Once reversible factors such as hypercalcemia have been corrected, the most common cause of severe renal failure in these patients is a tubulointerstitial pathology that results from the very high circulating concentrations of monoclonal immunoglobulin free light chains. These endogenous proteins can result in isolated proximal tubule cell cytotoxicity, tubulointerstitial nephritis and cast nephropathy (myeloma kidney). Less frequently, high levels of free light chains can lead to immunoglobulin light chain amyloidosis and light chain deposition disease, although these conditions are usually associated with insidious progression of renal failure rather than acute kidney injury. Unless there is rapid intervention, progressive and irreversible damage occurs, particularly interstitial fibrosis and tubular atrophy. Despite advances in our understanding of the pathogenesis of these processes there has been a gap in translating these achievements into improved patient outcomes. The International Kidney and Monoclonal Gammopathy Research Group was formed to address this need. In this Review, we discuss the mechanisms of disease and diagnostic approaches to patients with acute kidney injury complicating multiple myeloma. PMID- 22045245 TI - Circadian variation in ictus of aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Temporal patterns in aneurysmal subarachnoid hemorrhage (aSAH) may provide insight into modulation, and therefore, prevention of hemorrhage. We investigated the time of hemorrhage and its relationship to traditional risk factors among patients admitted with aSAH. METHODS: Admitted patients with aSAH were prospectively followed through outcomes and baseline demographics were abstracted through chart review. The group temporal distribution by hour of onset was summarized with cosinor nonlinear least squares. aSAH onset was gathered into night (2300-0500), morning (0500-1100), afternoon (1100-1700), and evening (0500 2300) daily phases. The odds ratio (OR) with 95% CI was calculated for having an aSAH during the morning, afternoon, and evening hours using night as a reference. Multinomial logit models were fitted using aSAH cases across time blocks to determine their associations with different risk factors. RESULTS: 202 patients had the hour of hemorrhage available, and 49 had phase identifiable [total 251: 38 (15%) night, 98 (39%) morning, 58 (23%) afternoon, 57 (23%) evening]. The peak hours of aSAH were between 0700 and 0800 representing 13% of the sample, with a significant cosinor-fitted phase of 7.33(95% CI 5.30, 9.36). For all aSAH cases, morning onset was significantly more common than night onset (OR = 2.58, 95% CI = 1.77-3.75). Nonsmokers were more likely to have aSAH in the morning than smokers (P = 0.043, OR = 3.10, 95% CI = 1.33-7.23). CONCLUSIONS: aSAH occur in a diurnal, morning prevalent pattern regardless of traditional aSAH risk factors. The association of these risk factors with existing onset patterns should be investigated in future studies. PMID- 22045246 TI - Geographic access to US Neurocritical Care Units registered with the Neurocritical Care Society. AB - BACKGROUND: Neurocritical care provides multidisciplinary, specialized care to critically ill neurological patients, yet an understanding of the proportion of the population able to rapidly access specialized Neurocritical Care Units (NCUs) in the United States is currently unknown. We sought to quantify geographic access to NCUs by state, division, region, and for the US as a whole. In addition, we examined how mode of transportation (ground or air ambulance), and prehospital transport times affected population access to NCUs. METHODS: Data were obtained from the Neurocritical Care Society (NCS), US Census Bureau and the Atlas and Database of Air Medical Services. Empirically derived prehospital time intervals and validated models estimating prehospital ground and air travel times were used to calculate total prehospital times. A discrete total prehospital time interval was calculated for each small unit of geographic analysis (block group) and block group populations were summed to determine the proportion of Americans able to reach a NCU within discrete time intervals (45, 60, 75, and 90 min). Results are presented for different geographies and for different modes of prehospital transport (ground or air ambulance). RESULTS: There are 73 NCUs in the US using ground transportation alone, 12.8, 20.5, 27.4, and 32.6% of the US population are within 45, 60, 75, and 90 min of an NCU, respectively. Use of air ambulances increases access to 36.8, 50.4, 60, and 67.3 within 45, 60, 75, and 90 min, respectively. The Northeast has the highest access rates in the US using ground ambulances and for 45, 60, and 75 min transport times with the addition of air ambulances. At 90 min, the West has the highest access rate. The Southern region has the lowest ground and air access to NCUs access rates for all transport times. CONCLUSIONS: Using NCUs registered with the NCS, current geographic access to NCUs is limited in the US, and geographic disparities in access to care exist. While additional NCUs may exist beyond those identified by the NCS database, we identify geographies with limited access to NCUs and offer a population-based planning perspective on the further development of the US neurocritical care system. PMID- 22045247 TI - A neurological complication of a uterine fibroid. AB - BACKGROUND: Uterine leiomyoma (or fibroid) can be associated with secondary polycythemia and venous thrombosis, but there has been no report of intracranial venous thrombosis associated with leiomyoma. METHODS: We describe a case report of a cerebral venous thrombosis associated with erythrocytosis and a uterine fibroid in a non-smoking female with no history of malignancy or hormone use. The hemoglobin and erythropoietin normalized after removal of her uterine fibroid. RESULTS: MRI/MRV of this 60-year-old cephalalgic female revealed extensive thrombus throughout the sagittal sinus and right transverse sinus. CT of the abdomen revealed a 16 * 13 * 12 cm solid mass arising for the uterus consistent with a uterine fibroid. PET scan was negative for malignancy. Hemoglobin on admission was 18.4 g/dl. Erythropoietin was 16.6 mIU/ml. One month after hysterectomy, her hemoglobin was 12.6 g/dl and her erythropoietin was 4.7 mIU/ml. CONCLUSIONS: Cerebral vein thrombosis is a potential complication of uterine fibroids with erythrocytosis. PMID- 22045248 TI - Strategies to decrease the risk of ventricular catheter infections: a review of the evidence. AB - The use of antibiotic-coated external ventricular catheters has been controversial among practitioners; although several papers have documented decreased adherence of microbes to catheters treated with antibiotics, there is no universally accepted practice standard for the use of coated catheters for the prevention of clinical infection. In this paper, we review the in vivo and in vitro evidence for antibiotic-coated catheters. PMID- 22045249 TI - Ultra-early aneurysmal rebleeding and brainstem destruction. AB - BACKGROUND: Early secondary neurologic deterioration after aneurysmal subarachnoid hemorrhage (SAH) may have many causes including rebleeding, hydrocephalus, parenchymal hematoma, or seizures. METHODS: Case report. RESULTS: A 69-year-old woman presented with thunderclap headache and nausea. A head computed tomography (CT) showed SAH. On initial evaluation she was awake, alert, and confused without focal neurologic deficits. Two episodes of marked clinical deterioration occurred, manifesting as acute unresponsiveness and fixed anisocoria. Serial head CTs showed massive extension of hemorrhage into the brainstem parenchyma and ventricles. CONCLUSIONS: Sudden clinical deterioration after SAH with coma and a fixed "blown" pupil may result from hemorrhage extension into the brainstem parenchyma rather than oculomotor nerve injury from compression or stretch. PMID- 22045250 TI - Zwitterionic sulfobetaine lipids that form vesicles with salt-dependent thermotropic properties. AB - We describe a class of zwitterionic sulfobetaine (SB) lipids with fascinating salt-dependent properties. SB lipids are zwitter-neutral across a broad pH range; however they have negative surface potentials in the presence of anions and two salt-dependent transition temperatures. These new SB lipids provide insight on the role of charge orientation at the membrane interface and may be useful components in drug delivery systems. PMID- 22045251 TI - [Sequelae of burns. Foreword]. PMID- 22045252 TI - Piezoelectric microelectromechanical resonant sensors for chemical and biological detection. AB - Piezoelectric microelectromechanical systems (MEMS) resonant sensors, known for their excellent mass resolution, have been studied for many applications, including DNA hybridization, protein-ligand interactions, and immunosensor development. They have also been explored for detecting antigens, organic gas, toxic ions, and explosives. Most piezoelectric MEMS resonant sensors are acoustic sensors (with specific coating layers) that enable selective and label-free detection of biological events in real time. These label-free technologies have recently garnered significant attention for their sensitive and quantitative multi-parameter analysis of biological systems. Since piezoelectric MEMS resonant sensors do more than transform analyte mass or thickness into an electrical signal (e.g., frequency and impedance), special attention must be paid to their potential beyond microweighing, such as measuring elastic and viscous properties, and several types of sensors currently under development operate at different resonant modes (i.e., thickness extensional mode, thickness shear mode, lateral extensional mode, flexural mode, etc.). In this review, we provide an overview of recent developments in micromachined resonant sensors and activities relating to biochemical interfaces for acoustic sensors. PMID- 22045253 TI - Neural mechanism of conflict control in a number interference task. AB - The electrophysiological bases of conflict control in a number interference task was measured in 21 healthy study participants using event-related brain potentials (ERPs). In the number interference task, participants were instructed to ignore the number words meaning and to report the number of the number words. The number words were 'two', 'three', or 'four'. We focused on the differences between the incongruent condition (e.g. 'two' written four times) and the congruent condition (e.g. four written four times). Scalp ERP analysis revealed that the incongruent condition elicited a more negative ERP deflection (N350-470) than the congruent condition between 350 and 470 ms, and a more late positive deflection (LPC) than the congruent condition between 550 and 650 ms. N350-470 was a critical sign of conflict monitoring in the early phase, and LPC mirrored conflict resolution in the terminal stage. The results provided evidence for the dissociation between conflict monitoring and conflict resolution in the number interference task. PMID- 22045254 TI - Reagents that block neuronal death from Huntington's disease also curb oxidative stress. AB - Patients with Huntington's disease suffer severe neuronal loss and signs of oxidative damage in the brain. Previously we found that primary neurons from embryonic cortex of mice bearing the Huntington's disease mutation (140 glutamines inserted into exon 1 of huntingtin) showed higher levels of reactive oxygen species before cell death. Here, we treated mutant neurons with known neuroprotective agents and determined the effects on neuronal survival and levels of reactive oxygen species. Primary neurons were exposed to the neurotrophin, brain derived neurotrophic factor, the antioxidant N-acetyl-cysteine or a specific inhibitor of glycogen synthase kinase 3-beta, SB216763. Each reagent increased the survival of the mutant neurons compared with untreated mutant neurons and also reduced the levels of reactive oxygen species to levels of wild type neurons. These results suggest that reducing the levels of reactive oxygen species may be necessary to protect neurons with the Huntington's disease mutation from cell death. PMID- 22045255 TI - Protein transduction into the mouse otocyst using arginine-rich cell-penetrating peptides. AB - The mouse otocyst, an anlage of the inner ear, is an attractive experimental target for developing treatment modalities for congenital inner ear diseases and for studying inner ear development. Poly-arginine (6-12 residues) is a cell penetrating peptide and can be used to deliver cargo into cells. Here, we achieved transutero delivery of enhanced green fluorescent protein (EGFP) fused to a nine-arginine peptide into mouse embryonic otocysts. The EGFP signal was detected both in the lining cells of the otocysts and in their vicinity at 18 h post injection. Mice injected with EGFP fused to a nine-arginine peptide had normal auditory and vestibular functions. These data suggest that protein transduction using poly-arginine may be a useful alternative strategy to commonly used gene delivery methods for delivering therapeutically relevant molecules to the developing inner ear. PMID- 22045256 TI - The involvement of the neurosteroid allopregnanolone in the antihyperalgesic effect of paroxetine in a rat model of neuropathic pain. AB - Paroxetine increases the levels of neurosteroids, such as allopregnanolone (AP), that influence the excitability of the central nervous system by positive allosteric modulation of gamma-aminobutyric acid type A receptors. Here, we investigated the role of AP synthesis on the paroxetine-induced antihyperalgesic effect in a rat model of neuropathic pain induced by lumbar spinal nerve ligation (SNL). Subcutaneous administration of paroxetine in SNL rats, dose-dependently decreased the probability of hyperalgesic response and increased AP levels in the spine but not in either brain or serum. Concomitant treatment with an inhibitor of the AP-synthesizing enzyme, finasteride, attenuated the paroxetine-induced antihyperalgesic effect as well as the paroxetine-induced increase in spinal AP levels. Intrathecal injection of exogenous AP mimicked the analgesic effects of paroxetine in vehicle-treated SNL rats, whereas no additional analgesic effects were observed in paroxetine-treated SNL rats. Our findings suggest that the antihyperalgesic effect of paroxetine in a rat neuropathic pain model is AP mediated. These results also suggest that pharmacological-based therapies targeting AP synthesis might be a promising treatment for neuropathic pain. PMID- 22045257 TI - Assessing spatial perception in aging using an adapted Landolt-C technique. AB - This study investigated luminance and texture-defined spatial information processing in normal aging using an adapted Landolt-C technique. Sensitivity to C target stimuli (optotypes) was measured for four age groups: 18-34, 35-49, 50-64, and 65+ years. Participants indicated optotype gap-opening orientations (up, down, left, or right) at different levels of luminance or texture contrast. Although sensitivity did not differ across age group for the luminance-defined optotypes, sensitivity for texture-defined optotypes for the 65+ years age group was significantly decreased relative to that of the youngest group (18-34 years). Results suggest that age-related changes in visual function can be dissociated at different levels of processing, and may be better defined using stimuli that necessarily depend on higher levels of neural functioning to be perceived. PMID- 22045258 TI - The near-miss effect in slot-machine gambling: modulation of feedback-related negativity by subjective value. AB - Near-miss plays an important role in the development of gambling addictions. In this study, we measured the neural correlates of the process by which near-miss outcomes are evaluated in simplified, static, slot-machine gambling using event related potentials. Analysis of event-related potentials revealed that the size of FRN (feedback-related negativity) for a near miss is between the full miss and the win. These results suggest that participants distinguish among near misses, full misses, and wins during the early evaluation phase. The subjective value and objective value of outcome were assessed separately to discuss FRN on outcome evaluation. It is suggested that FRN is mediated not only by the objective value of outcomes but also by the subjective value of feedback. PMID- 22045259 TI - The relationship in gating effects between short-latency and long-latency somatosensory-evoked potentials. AB - We investigated the relationship between short-latency and long-latency somatosensory-evoked potentials (SEPs) relating to voluntary movement. In general, the amplitudes of short-latency components in SEPs are attenuated during movement, whereas those of long-latency are enhanced, and this phenomenon is termed 'gating effects'. This study aimed to examine the relationship of changes in amplitude between short-latency and long-latency SEPs. SEPs were recorded from 11 participants at Fz, Cz, Pz, and C4' by stimulating the left median nerve. Two tasks were conducted; Control and Movement. In Control, the participant was asked to relax with no specific task. In Movement, the participant was encouraged to continue a rapid drumming motion of all fingers of the left hand at a self-paced rate. The amplitudes of short-latency SEPs, the P25 at C4' and N30 at Fz, were significantly smaller in the Movement than Control condition. By contrast, the amplitudes of long-latency SEPs, the N140 at Fz, Cz, and Pz were significantly larger in Movement than Control condition. Moreover, a significant positive correlation was observed in the rate of amplitude change between the frontal N30 and vertex N140, indicating that for the participants with a frontal N30 of smaller amplitude during Movement, the amplitude of the vertex N140 was smaller. We inferred that the neural activities in movement-related cortices affected the sources for the frontal N30 and vertex N140 in the same neuronal network simultaneously. PMID- 22045260 TI - White matter integrity and math performance in pediatric multiple sclerosis: a diffusion tensor imaging study. AB - Multiple sclerosis is associated with reduced white matter integrity and deficits in key cognitive processes important for arithmetic. This study examined the relationship between white matter microstructure and academic ability in 31 youths with multiple sclerosis (aged 11-19 years) and 34 demographically matched controls. Using diffusion tensor imaging, fractional anisotropy was calculated in corpus callosum and in lateralized hemispheric lobes. Difficulties with written arithmetic ability were observed in 26% of patients. Arithmetic ability correlated with fractional anisotropy values across all segments of the corpus callosum and in right frontal and parietal regions, controlling for age (r values >0.5, P<0.005). Findings highlight the functional impact of compromised white matter microstructure across diffuse regions of the brain on mathematical ability. PMID- 22045261 TI - Establishment of a prolonged pancreas preservation model for islet isolation research in mice. AB - Establishing a prolonged pancreas preservation model in a small animal is important for islet isolation research. Use of a rat pancreas model has been reported, but no published reports have used a mouse pancreas for prolonged cold preservation prior to islet isolation. For the model, a mouse is preferred over a rat because of its small size, well-known immune characterization, and variety of gene-modulated models. In the present study, we established a prolonged pancreas preservation model in a mouse for islet isolation research. The collagenase solution was injected successfully after 24 and 48 h cold preservations in University of Wisconsin solution, and islets could be isolated from both groups of preserved pancreata. The islet yields from the control, 24 h preserved, and 48 h preserved pancreata were 183.9 +/- 13.9, 128.5 +/- 15.5, and 24.6 +/- 12.9 per pancreas, respectively. The propidium iodide-positive area assay was significantly increased in both preserved groups, and insulin secretion levels in response to 20.0 mM glucose and stimulation indices were significantly decreased in the 48 h preserved group. Inflammation-related genes mRNA levels were significantly upregulated in the 24 h preserved group, as previously shown in the human model. Thus, this model might be useful for prehuman islet isolation screening research, reserving research using human pancreata for the most promising approaches. PMID- 22045262 TI - Loss of Bmal1 leads to uncoupling and impaired glucose-stimulated insulin secretion in beta-cells. AB - The circadian clock has been shown to regulate metabolic homeostasis. Mice with a deletion of Bmal1, a key component of the core molecular clock, develop hyperglycemia and hypoinsulinemia, suggesting beta-cell dysfunction. However, the underlying mechanisms are not fully known. In this study, we investigated the mechanisms underlying the regulation of beta-cell function by Bmal1. We studied beta-cell function in global Bmal1-/- mice, in vivo and in isolated islets ex vivo, as well as in rat insulinoma cell lines with shRNA-mediated Bmal1 knockdown. Global Bmal1-/- mice develop diabetes secondary to a significant impairment in glucose-stimulated insulin secretion (GSIS). There is a blunting of GSIS in both isolated Bmal1-/- islets and in Bmal1 knockdown cells, as compared to controls, suggesting that this is secondary to a loss of cell-autonomous effect of Bmal1. In contrast to previous studies, in these Bmal1-/- mice on a C57Bl/6 background, the loss of stimulated insulin secretion, interestingly, is with glucose but not to other depolarizing secretagogues, suggesting that events downstream of membrane depolarization are largely normal in Bmal1-/- islets. This defect in GSIS occurs as a result increased mitochondrial uncoupling with consequent impairment of glucose-induced mitochondrial potential generation and ATP synthesis, due to an upregulation of Ucp2. Inhibition of Ucp2, in isolated islets, leads to a rescue of the glucose-induced ATP production and insulin secretion in Bmal1-/- islets. Thus, Bmal1 regulates mitochondrial energy metabolism to maintain normal GSIS and its disruption leads to diabetes due to a loss of GSIS. PMID- 22045263 TI - The redundant role of JAK2 in regulating pancreatic beta-cell mass. AB - Janus kinase (JAK) 2 is a non-receptor tyrosine kinase that mediates the downstream effects of various growth factors, including growth hormone, prolactin, placental lactogen, and erythropoietin (EPO). EPO is a hematopoietic growth factor that is largely known for its role in promoting proliferation, differentiation and survival of cells in the erythroid lineage. Global loss of the EPO receptor (EPO-R) has been shown to be embryonically lethal in mice due to anemia attributed to defects in erythropoiesis. Interesting, mice with global deficiency of JAK2 share a similar developmental phenotype as the EPO-R knockout mice, demonstrating that JAK2 is essential in eliciting the biological effects of EPO, particularly in erythrocytosis. Recent studies from our group have shown that exogenous EPO protects mice against diabetes through direct effects on pancreatic beta-cells, and these protective effects are dependent on the presence of JAK2 in the beta-cells. Here, we briefly highlight the cytoprotective effects of exogenous EPO in the pancreatic beta-cells as well as our new findings on the redundant role of JAK2 in beta-cell expansion after high-fat feeding in mice. PMID- 22045264 TI - Proangiogenic effects of environmentally relevant levels of bisphenol A in human primary endothelial cells. AB - Bisphenol A (BPA) is widely used in the manufacturing of consumer products such as plastic food containers and food cans. Experimental studies suggest a relationship between exposure to BPA and changes in metabolic processes and reproductive organs. Also, epidemiological studies report an association between elevated exposure to BPA and cardiovascular disease and diabetes. Although alterations in the vascular endothelium are implicated in pathological conditions associated with BPA, little is known about the effects of BPA in the human endothelium. This study aimed to investigate the effects of 0.1 nM-1 MUM of BPA on selected biomarkers of endothelial dysfunction, inflammation, and angiogenesis in human umbilical vein endothelial cells (HUVEC). The mRNA expression of biomarkers was assayed using qRT-PCR, and the production of nitric oxide and reactive oxygen species was measured using the H(2)DCFDA and the DAF-FM assays. The effect of BPA on phosphorylated eNOS was examined using Western blot and immunofluorescence, and the endothelial tube formation assay was used to investigate in vitro angiogenesis. BPA (<=1 MUM) increased the mRNA expression of the proangiogenic genes VEGFR-2, VEGF-A, eNOS, and Cx43 and increased the production of nitric oxide in HUVEC. Furthermore, BPA increased the expression of phosphorylated eNOS and endothelial tube formation in HUVEC. These studies demonstrate that environmentally relevant levels of BPA have direct proangiogenic effects on human primary endothelial cells in vitro suggesting that the human endothelium may be an important target for BPA. PMID- 22045265 TI - Abnormal multifocal ERG findings in patients with normal-appearing retinal anatomy. AB - To evaluate eyes with abnormal visual fields and multifocal electroretinograms (mfERGs) but normal-appearing frequency-domain optical coherence tomography (fdOCT) scans, the thicknesses of the outer retinal layers were measured. A total of 25 eyes from 17 patients, including 15 eyes previously tested (Dale et al. in Doc Ophthalmol 120(2):175-186, 2009) were examined. All patients were evaluated with standard automated perimetry (SAP) using the 24-2 and/or 10-2 program (Zeiss Meditec), mfERG with 103 hexagons (Veris, EDI), and fdOCT imaging (3DOCT-2000, Topcon) with scans of the macula. All patients had reliable visual fields showing macular defects and good quality mfERG and fdOCT results. The mfERG results were classified as abnormal based on decreased amplitudes and/or increased latencies corresponding to the abnormal visual field. Based on visual inspection, three experienced observers classified the fdOCT scans as normal or inconclusive, as opposed to clearly abnormal. Retinal layers of the fdOCT scans were manually segmented with the aid of a computer program and compared to mean thicknesses from 20 controls. The thicknesses of the outer segment plus retinal pigment epithelium, total receptor, and inner nuclear layers were measured. Quantitative analysis of fdOCT scans demonstrated thinning of the outer retina in some scans that was not readily apparent on visual inspection. One or more of the outer retinal layers was significantly thinner in 15 of the 25 eyes. The absence of significant thinning in the other 10 eyes represents instances in which functional loss measured by visual fields and mfERGs can precede clear structural changes on fdOCT. PMID- 22045266 TI - Calliphora vicina human myiasis: a case report. PMID- 22045267 TI - A review of current anesthetic concerns and concepts for cesarean hysterectomy. AB - PURPOSE OF REVIEW: Peripartum hemorrhage still remains a significant source of maternal morbidity and mortality worldwide. Abnormal placentation is one of the leading causes of peripartum hemorrhage. RECENT FINDINGS: The incidence of abnormal placentation is increasing secondary to the increased incidence of cesarean section. The main forms of abnormal placentation include placenta accreta, placenta previa and low-lying placenta. Historically placenta accreta was an incidental finding at the time of delivery and was associated with high maternal morbidity and mortality. The development of new imaging techniques such as magnetic resonance imaging and transvaginal color Doppler sonography has allowed antenatal diagnosis of this condition and elective preoperative planning of the obstetric and anesthetic management of these patients. Optimum management for most cases requires elective cesarean hysterectomy, performed ideally at about 34 weeks' gestation. SUMMARY: The present article is an update on the state of-the art multidisciplinary management of parturients undergoing cesarean hysterectomy with special emphasis on anesthetic considerations. It summarizes the prevention, management and treatment of obstetric hemorrhages in parturients with abnormal placentation and highlights recent advances and developments. The obstetrician and the obstetric anesthesiologist must know, on the spot, how to deal with abnormal placentation-related peripartum bleeding. A multidisciplinary approach results in best outcomes. PMID- 22045268 TI - A 2020 vision for women's health. PMID- 22045269 TI - Longitudinal extensive transverse myelitis--it's not all neuromyelitis optica. AB - Longitudinal extensive transverse myelitis (LETM) is defined as a spinal cord lesion that extends over three or more vertebrae, as seen on MRI of the spine. The clinical presentation of a patient with LETM is often dramatic and can consist of paraparesis or tetraparesis, sensory disturbances, and gait, bladder, bowel and/or sexual dysfunction. LETM is a characteristic feature of neuromyelitis optica, but such spinal lesions can also occur in various other autoimmune and inflammatory diseases that involve the CNS--such as multiple sclerosis, sarcoidosis or Sjogren syndrome--or in infectious diseases with CNS involvement. Patients with a neoplastic disorder or traumatic spinal cord injury can also present with longitudinal spinal lesions. In this Review, the signs and symptoms that suggest various etiologies and differential diagnoses of LETM are described, and illustrated by educational case studies. The best therapeutic options for patients with each diagnosis are also discussed. PMID- 22045271 TI - Characterization of a bacteriophage, isolated from a cow with mastitis, that is lytic against Staphylococcus aureus strains. AB - Methicillin-resistant strains of Staphylococcus aureus (MRSA) are now the most commonly reported antibiotic-resistant bacterium in clinical settings. Therefore, there is an urgent need to develop novel antibacterial agents to control this pathogen. Bacteriophage therapy is a potential alternative treatment for MRSA infections. The objective of this study was characterization of a novel virulent bacteriophage (MSA6) isolated from a cow with mastitis. Electron microscopy showed its resemblance to members of the family Myoviridae, with an isometric head (66 nm) and a long contractile tail (173 nm). The genome of phage MSA6 was tested by pulsed-field gel electrophoresis and estimated to be about 143 kb. It exhibited rapid adsorption (>82% in 5 min), a short latent period (15 min) and a relatively small burst size (23 PFU/cell). Isolated phage was capable of infecting a wide spectrum of staphylococcal strains of both human and bovine origin. The results of this investigation indicate that MSA6 is similar to other bacteriophages belonging to the family Myoviridae (Twort, K, G1, 812) that have been successfully used in bacteriophage therapy. PMID- 22045270 TI - Neuropsychological assessment of patients with dementing illness. AB - Neuropsychological assessment has a distinct role in the detection and monitoring of cognitive and functional changes associated with dementing illness. Molecular, structural and functional neuroimaging studies have advanced our understanding of the anatomy and physiology underlying neurodegenerative disease; however, the overlap in pathological features of different dementia-associated diseases limits the information that can be obtained by these methods. Incorporation of information obtained from multiple sources can help to increase diagnostic and prognostic accuracy. Neuropsychological test findings provide unique value as biomarkers of dementia, as differentiators of disease topography and in the estimation of disease risk and trajectory. However, psychometric test properties- such as construct validity, stability and the use of appropriate norms--must be understood, because they influence both the application of neuropsychological tests and the interpretation of their results. Finally, measurement of cognitive strengths and weaknesses in patients at risk of dementia can be helpful to predict changes in functional abilities, design appropriate and effective interventions, and assist family and health-care providers in the planning of the patient's future care needs. This Review describes the key characteristics of neuropsychological testing in the assessment of patients at risk of dementia. PMID- 22045272 TI - Mapping utility scores from the Barthel index. AB - PURPOSE: It is not always possible to collect utility-based outcome data, like EQ 5D, needed for conducting economic evaluations in populations of older people. Sometimes, information on other non-utility outcome measures may have been collected. This paper examines the possibility of mapping the EQ-5D from a non utility-based outcome, the Barthel index. METHODS: Data for 1,189 UK intermediate care patients were used. Ordinary least squares (OLS), censored least absolute deviations (CLAD) estimator and multinomial logistic (ML) models were used. The mean absolute error (MAE) and root-mean-squared error (RMSE) were used to estimate the predictive accuracy of eight regression models. Validation of primary models was carried out on random samples of data collected at admission and discharge. RESULTS: Models where the EQ-5D was entered as a continuous dependent variable and Barthel dimensions used as explanatory variables performed better. CLAD performed best on MAE and OLS on the RMSE, while the ML performed the worst on both measures. The CLAD predicted EQ-5D scores that matched the observed values more closely than the OLS. CONCLUSIONS: It is possible to reasonably predict that the EQ-5D from the Barthel using regression methods and the CLAD model (4) is recommended. PMID- 22045274 TI - Duodenal MALToma with gastric outlet obstruction. case report and review of literature. PMID- 22045273 TI - Dietary, endocrine, and metabolic factors in the development of colorectal cancer. AB - INTRODUCTION: Colorectal cancer is the third cause of death in industrialized countries. Genetic susceptibility and diet are determinant of cancer risk and tumor behavior. Variation in cancer incidence among and within populations with similar dietary patterns suggests that an individual response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenomics, defined as the interaction between nutrition and an individual genome, will likely provide important clues about responders and non-responders to nutritional intervention. DISCUSSION: Epidemiological and experimental studies suggest a protective role of some normal components of daily diet (fish oil, milk, and vegetables), estrogens, and phytoestrogens in colorectal cancer. The effect of estrogen seems to be mediated by their binding to estrogen receptor beta (ER-beta), one of the two estrogen receptors with high affinity for these hormones. Very recently, the demonstration of an involvement of ER-beta in the development of adenomatous polyps of the colon has also been documented, suggesting the use of selective ER-beta agonists in primary colorectal cancer prevention. Phytoestrogens are plant-derived compounds that structurally and functionally act as estrogen agonists in mammals. They are characterized by a higher binding affinity to ER-beta as compared to estrogen receptor alpha (ER-alpha), the other estrogen receptor subtype. These biological characteristics explain why the administration of phytoestrogens does not produce the classical side effects associated to estrogen administration (cerebro- and cardiovascular accidents, higher incidence of endometrial and breast cancer) and makes these substances potential candidates for colorectal cancer prevention. PMID- 22045275 TI - Primary Signet Ring Cell Anal Adenocarcinoma. PMID- 22045276 TI - Activity of Imatinib Mesylate in Metastatic Anorectal Melanoma: A Case Report. PMID- 22045277 TI - Localization of ORC1 during the cell cycle in human leukemia cells. AB - The interaction of the origin recognition complex (ORC) with replication origins is a critical parameter in eukaryotic replication initiation. In mammals the ORC remains bound except during mitosis, thus the localization of ORC complexes allows localization of origins. A monoclonal antibody that recognizes human ORC1 was used to localize ORC complexes in populations of human MOLT-4 cells separated by cell cycle position using centrifugal elutriation. ORC1 staining in cells in early G1 is diffuse and primarily peripheral. As the cells traverse G1, ORC1 accumulates and becomes more localized towards the center of the nucleus, however around the G1/S boundary the staining pattern changes and ORC1 appears peripheral. By mid to late S phase ORC1 immunofluorescence is again concentrated at the nuclear center. During anaphase, ORC1 staining is localized mainly in the pericentriolar regions. These findings suggest that concerted movements of origin DNA sequences in addition to the previously documented assembly and disassembly of protein complexes are an important aspect of replication initiation loci in eukaryotes. PMID- 22045278 TI - Multiple ectopic leiomyomas of the abdominal rectus muscles after gasless laparoscopic uterine myomectomy. AB - PURPOSE: To describe and analyze the first case of multiple ectopic leiomyomas of the abdominal rectus muscles in a patient who had undergone gasless laparoscopic uterine myomectomy (GLM) 10 years before. METHODS: A 41-year-old woman, who had undergone GLM 10 years before, having presented multiple palpable masses of the abdominal wall, underwent minilaparotomic excision of six abdominal masses. RESULTS: Six round well-circumscribed masses of the abdominal rectus muscles, measuring, respectively, 3.8 * 1.7, 2.9 * 0.9, 0.8 * 0.5, 0.7 * 0.3, 10 * 0.8 and 0.5 * 0.4 cm, were excised. The major lesion was situated close to the right trocar site of the previous GLM, the other smaller tumors were located in the umbilical area and left abdominal region. On histopathologic examination, the abdominal lumps were categorized as leiomyoma. CONCLUSIONS: Ectopic leiomyomatosis is an uncommon complication after GLM, and does not justify follow up in all asymptomatic cases. However, the gynecologists should bear this unusual condition in mind, and inform the patients that leiomyoma fragments can grow in ectopic sites. PMID- 22045279 TI - Pure motor monoparesis due to ischemic stroke. AB - BACKGROUND: Pure motor monoparesis (PMM), an isolated motor deficit that occurs after ischemic stroke (IS) in a single arm or leg without accompanying cranial or sensory dysfunction, is rare and easily misdiagnosed as other causes of weakness. REVIEW SUMMARY: Cortical infarctions of the precentral knob and the anterior cerebral artery territory (for upper and lower limbs, respectively) are the most commonly reported lesion sites in PMM. Other sites include the subcortex, corona radiata, internal capsule, and brainstem; these sites are cited less frequently than those afflicted by cortical infarctions. PMM shows a complex weakness pattern; however, distal-dominant weakness, as well as the absence of pyramidal signs is most commonly observed in PMM owing to IS. Nevertheless, the overall prognosis is generally good. CONCLUSIONS: Physicians should carefully assess acute monoparesis, particularly in elderly patients with conventional risk factors, and should include IS in the differential diagnosis. Diffusion-weighted imaging is the most useful tool for diagnosing PMM owing to IS. PMID- 22045280 TI - Same or opposite? Association of head-movement weakness with limb paresis in stroke. AB - OBJECTIVES: The precise innervation of the sternocleidomastoids is uncertain. Of clinical interest is whether a unilateral hemispheric lesion leads to an ispilateral or contralateral sternocleidomastoid weakness. METHODS: Sternocleidomastoid strength was assessed in 124 consecutive acute stroke patients during yaw, pitch, and roll head movements. This was correlated with limb paresis and neuroimaging findings. RESULTS: The incidence and the degree of sternocleidomastoid paresis were low (16.9%). In all cases, head rotation weakness away from the affected hemisphere was observed. Lateral tilt and vertical head rotations were unaffected. No weakness was detected in lesions that did not cause manifest limb paresis. CONCLUSIONS: Our data point to an ipsihemispheric sternocleidomastoid control. Sternocleidomastoid paresis in stroke is expected only with concomitant limb paresis and is always less severe. Head tilt is not affected probably due to sparing of ancillary neck-muscle function. PMID- 22045281 TI - Role of greater occipital nerve blocks and trigger point injections for patients with dizziness and headache. AB - BACKGROUND: The trigeminocervical system is integral in cervicogenic headache. Cervicogenic headache frequently coexists with complaints of dizziness, tinnitus, nausea, imbalance, hearing complaints, and ear/eye pain. Controversy exists as to whether this constellation of symptoms may be cervically mediated. OBJECTIVES: To determine whether a wider spectrum of cervically mediated symptoms exist, and to investigate a potential role of greater occipital nerve blocks (GON) and trigger point injections (TPI) in these patients. METHODS: Retrospective review of GON/TPI performed in a tertiary otoneurology/headache clinic from May 2006 to March 2007 for suspected cervically mediated symptoms. Data included chief complaint, secondary symptoms, response to injection, pre-GON/TPI posterior vertex sensation changes to pinprick, cervical spine examination, and response to vibration of cervical and suboccipital musculature. RESULTS: Total number of 147 patients were included. Chief complaints in decreasing frequency: dizziness (93%), tinnitus (4%), headache (3%), and ear discomfort (0.7%). Overall symptoms in decreasing frequency: dizziness (97%), headache (88%), neck pain (63%), tinnitus (23%), and ear discomfort (22%). Improvements after GON/TPI: neck range of motion (71%), headache (57%), neck pain (52%), ear discomfort (47%), dizziness (46%), and tinnitus (30%). Dizziness responders had neck position asymmetries (84%), reproducible dizziness by cervical and suboccipital musculature vibration (75%), and preinjection posterior vertex sensory changes (60%). CONCLUSIONS: A wider spectrum of cervically mediated symptoms may exist by influence of trigeminocervical and vestibular circuitry through cervical afferent neuromodulation. Certain examination findings may help to predict benefit from GON/TPI. PMID- 22045282 TI - Rasagiline: time to onset of antiparkinson effect is similar when used as a monotherapy or adjunct treatment. AB - OBJECTIVE: Rasagiline, a monoamine oxidase type B inhibitor, is indicated for both the initial treatment of Parkinson disease (PD) and as adjunctive (add-on) treatment for patients already taking dopaminergic therapy. This open-label prospective community-based clinical trial was designed to determine the time-to onset and the magnitude of the beneficial effects of rasagiline in PD patients. METHODS: Patients received rasagiline of 1.0 mg once daily as monotherapy or 0.5 mg once daily as adjunct therapy (adjunct therapy dose could be increased to 1 mg/d if clinically indicated) for 12 weeks. Dietary restrictions and recommendations regarding concurrent antidepressant treatment consistent with the Food and Drug Administration (FDA) regulations were in keeping with typical usage. Effectiveness was measured as change from baseline in bradykinesia scores and physicians' and patients' global impression. Patients were prospectively monitored for treatment emergent dopaminergic side effects, tyramine reactions, and possible interactions with commonly used antidepressants. RESULTS: Objective and subjective measures of symptom severity improved at 1 week in 272 PD patients treated with once-daily rasagiline (n=123 monotherapy, n=149 adjunct therapy). The magnitude of beneficial effect was similar in monotherapy and adjunct therapy patients. No significant dopaminergic side effects, tyramine reactions, or interactions with antidepressants were observed in the 12-week trial. CONCLUSIONS: Rasagiline has a measurable beneficial effect on PD symptoms within 1 week of treatment. Rasagiline has a similar magnitude of benefit in monotherapy and adjunct therapy patients. Adverse interactions between antidepressants and rasagiline were not observed in patients in this trial. The usual use of rasagiline in community neurology practice, consistent with the FDA labeling, seems safe and effective. PMID- 22045283 TI - Nonconvulsive status epilepticus: value of a benzodiazepine trial for predicting outcomes. AB - OBJECTIVES: Managing nonconvulsive status epilepticus (NCSE) poses many challenges that would benefit from additional early measures to predict patient outcomes. Here, we evaluate clinical and electroencephalographic responses to an acute antiepileptic drug trial as an added measure for predicting outcomes in patients presenting with suspected NCSE. METHODS: We analyzed all patients referred to our Neurology Service with suspected NCSE assessed by a standard acute intravenous (IV) benzodiazepine (BDZ) protocol. We correlated patients' clinical and electrographic (EEG) responses to the BDZ trial with their subsequent outcomes, including survival, recovery of consciousness, and functional status at hospital discharge. RESULTS: From 1990 to 2001, we identified 62 patients with NCSE who were initially evaluated with an acute IV BDZ protocol trial. A favorable clinical response with improvement in consciousness was observed in 22 patients (35%), whereas 40 (65%) were clinical nonresponders. All of the positive clinical responders (100%) survived, recovered consciousness, and exhibited good functional outcomes. In contrast, outcomes were significantly poorer (P<0.001) for the clinical nonresponders; only 14 (35%) recovered consciousness and 22 (55%) survived, with 59% of those survivors demonstrating poor functional outcomes. EEG improvement with BDZs also predicted better outcome, but it was less robust than the clinical response, with better subsequent recovery of consciousness (P<0.05), but not functional outcome or survival. CONCLUSIONS: This study demonstrates that a clinical and, to a lesser degree, EEG response to an acute trial of IV BDZs are predictive of subsequent outcome in patients with suspected NCSE, and warrant further consideration and investigation for assessing and managing patients. PMID- 22045284 TI - Herpes simplex virus type 1 in saliva of patients with vestibular neuronitis: a preliminary study. AB - OBJECTIVES: Vestibular neuronitis (VN) is an inflammatory disease of the vestibular nerve, presumably caused by reactivation of the herpes simplex virus type l (HSV-1). We hypothesized that HSV-1 might be detected in saliva of patients with VN due to migration of the reactivated virus from the vestibular ganglia to the parotid gland. METHODS: Twenty-one patients with VN and 15 healthy controls participated. HSV-1 DNA detection was performed using the real-time polymerase chain reaction method. Sera were collected and stored to be later analyzed for immunoglobulin (Ig) G and IgM antibody titers against HSV-1 by immunofluorescence and enzyme linked immunosorbent assay methods, respectively. RESULTS: HSV-1 was detected in saliva of 14% of VN patients and in 6% of controls (P>0.05). Serological testing revealed borderline IgM (optical density+/-10% average of 2 cut off serums) antibodies to HSV-1 in 75% of patients versus 13% of controls (P=0.01). The IgG antibody test was positive in 17 of 20 patients and borderline (IgG <=1:16) in 2 of 20 patients tested whereas 13 of 15 controls had positive IgG test results (P>0.05). CONCLUSIONS: In this preliminary study we found serological evidence of higher exposure of patients with VN to HSV-1 in the past. We were not able to demonstrate that the virus can be detected in saliva of VN patients as evidence for herpetic infection or reactivation. PMID- 22045285 TI - Internal carotid artery dissection heralded by an oculomotor nerve palsy: case report and literature review. AB - INTRODUCTION: Acute oculomotor nerve (CN III) palsies are commonly attributed to microvascular disease or compressive lesions and aneurysms, but may rarely be associated with ischemic large vessel disease. We report a case of an extracranial internal carotid artery (ICA) dissection heralded by CN III palsy with review of the relevant literature. CASE REPORT: A 24-year-old right-handed man presented with right-sided weakness preceded by vomiting 2 days earlier. The following day, the family noted his left eye to be deviated outward with enlarged pupil and droopy eyelid. On the day of admission, he had a fall owing to right sided weakness. His neurological examination revealed significant aphasia, left third nerve palsy, right homonymous hemianopsia, and right-sided hemiplegia with hemisensory deficits. A brain magnetic resonance image showed an acute ischemic infarct in the left middle cerebral artery distribution without mass effect. Magnetic resonance angiogram showed a left extracranial internal cerebral artery (ICA) dissection with absence of flow within the distal cervical and intracranial ICA segments. He underwent a decompressive left hemicraniectomy with partial improvement in his deficits. DISCUSSION: Oculomotor nerve palsy as a result of ICA disease is a rare entity but has been reported in cases of stenosis, occlusion, and dissection. It is likely to be caused by hypoperfusion of CN III secondary to low flow or microembolism in the arteries feeding the nerve. The risk of CN III palsy in patients with ICA disease is higher in the presence of a fetal posterior cerebral artery. CONCLUSIONS: Acute oculomotor nerve palsies with pupillary involvement warrant thorough investigation. When routine work-up fails to elucidate an etiology, extracranial carotid pathology should be considered. PMID- 22045286 TI - Two cases of delayed-onset transient global amnesia after saline-contrast transthoracic echocardiography. AB - INTRODUCTION: We present 2 cases of transient global amnesia (TGA) with delays of 1 and 2 hours after saline-contrast transthoracic echocardiography. The unique presentation in these cases may help elucidate the possible mechanisms underlying TGA. CASES: (1) A 63-year-old woman admitted for lower extremity arterial thrombosis with TGA onset 1 hour after saline-contrast echocardiography. (2) A 75 year-old woman admitted to rule out myocardial infarction with TGA onset 2 hours after saline-contrast echocardiography. CONCLUSIONS: The precipitating events of TGA are varied and an understanding of the mechanism(s) underlying the phenomenon is incomplete. However, the presence of a delay after the trigger event as described in these cases is unique and informative in that it lends strength to some proposed mechanisms over others in this subset of TGA presentations. PMID- 22045287 TI - Exposure to high dosage trihexyphenidyl during pregnancy for treatment of generalized dystonia: case report and literature review. AB - INTRODUCTION: Trihexyphenidyl is 1 of the most effective agents for treatment of young-onset dystonia. As such, women of childbearing potential use trihexyphenidyl despite inadequate information about potential effects on pregnancy, labor, and fetal development. CASE REPORT: We report 2 uncomplicated pregnancies in 1 woman with early-onset, sporadic, primary generalized dystonia (DYT1 negative) treated with high dosage trihexyphenidyl and review the literature on antidystonic agents and pregnancy. CONCLUSION: Although there is limited data, our case demonstrates that high-dosage trihexyphenidyl treatment is not necessarily a contraindication to pregnancy. PMID- 22045288 TI - Intraspinal tumors accompanied by hydrocephalus: case report, systematic review, and discussion of treatment strategy. AB - INTRODUCTION: Intraspinal tumor accompanied by hydrocephalus is an unusual but well-documented condition. Although many authors have proposed a variety of possible causes, the etiology is still unknown. Meanwhile, little has been discussed about the treatment strategy. CASE REPORT: We report a case of intraspinal neurinoma accompanied by hydrocephalus. The patient presented with numbness and weakness of the legs, incontinence, and headache. Computed tomography scan demonstrated hydrocephalus and obvious peri-ventricular edema. She was given ventriculoperitoneal (V-P) shunt, but the shunt system had to be removed due to a postoperative intracranial hematoma. To our surprise, the hydrocephalus resolved after the tumor resection. We reviewed the literature and discussed a reasonable treatment strategy for this condition. CONCLUSIONS: In patients presenting with hydrocephalus of unclear etiology, attention should be paid to possible spine pathology. If an intraspinal neurinoma is found, a V-P shunt is usually not necessary. A V-P shunt is only indicated when hydrocephalus does not improve after tumor resection. PMID- 22045289 TI - Safety and efficacy of ultrasound-enhanced thrombolysis in the treatment of acute middle cerebral artery infarction: a critically appraised topic. AB - BACKGROUND: Despite appropriate therapy with intravenous (IV) tissue plasminogen activator (tPA), a significant proportion of patients with acute middle cerebral artery (MCA) infarction continue to suffer residual disability or death. The therapeutic use of transcranial Doppler ultrasonography (TCD) concomitantly with IV tPA is speculated to increase recanalization rates and improve clinical outcomes in patients with acute MCA stroke. OBJECTIVE: To critically appraise the evidence concerning the safety and efficacy of the simultaneous delivery of IV tPA and continuous TCD monitoring as an acute therapy in patients with MCA territory infarction. METHODS: The objective was addressed through the development of a structured, critically appraised topic. This incorporated a clinical scenario, background information, a structured question, literature search strategy, results, critical appraisal, clinical bottom line, and expert commentary from vascular neurology. RESULTS: In a multicenter phase II randomized controlled study, 126 patients with acute MCA stroke were randomized to receive treatment with IV tPA and continuous TCD monitoring or placebo monitoring. Complete recanalization or dramatic clinical recovery within 2 hours after the administration of a tPA bolus occurred in 31 patients in the target group (49%), as compared with 19 patients in the control group (30%); P=0.03. At 3 months, of the patients eligible for follow-up, 22 of 53 (42%) in the target group and 14 of 49 (29%) in the control group had favorable outcomes; P=0.20. Four symptomatic intracerebral hemorrhages were noted in each group. CONCLUSIONS: Therapeutic use of continuous TCD monitoring concomitantly with IV tPA increases recanalization rates in patients with acute MCA stroke relative to treatment with IV tPA alone without increasing the complication of intracerebral hemorrhage. PMID- 22045290 TI - Coin rotation test. PMID- 22045291 TI - Combining rails and anchors with laser forcing for selective manipulation within 2D droplet arrays. AB - We demonstrate the combination of a rails and anchors microfluidic system with laser forcing to enable the creation of highly controllable 2D droplet arrays. Water droplets residing in an oil phase can be pinned to anchor holes made in the base of a microfluidic channel, enabling the creation of arrays by the appropriate patterning of such holes. The introduction of laser forcing, via laser induced thermocapillary forces to anchored droplets, enables the selective extraction of particular droplets from an array. We also demonstrate that such anchor arrays can be filled with multiple, in our case two, droplets each and that if such droplets have different chemical contents, the application of a laser at their interface triggers their merging and a chemical reaction to take place. Finally by adding guiding rails within the microfluidic structure we can selectively fill large scale arrays with monodisperse droplets with significant control over their contents. In this way we make a droplet array filled with 96 droplets containing different concentrations of fluorescent microparticles. PMID- 22045292 TI - Validation, repeatability and reproducibility of a noninvasive instrument for measuring thoracic and lumbar curvature of the spine in the sagittal plane. AB - BACKGROUND: The need for early identification of postural abnormalities without exposing patients to constant radiation has stimulated the development of instruments aiming to measure the spinal curvatures. OBJECTIVE: To verify the validity, repeatability and reproducibility of angular measures of sagittal curvatures of the spine obtained using an adapted arcometer, by comparing them with Cobb angles of the respective curvatures obtained by using X-rays. METHODS: 52 participants were submitted to two procedures designed to evaluate the thoracic and lumbar curvatures: (1) X-ray examination from which the Cobb angles (CA) of both curvatures were obtained, and (2) measuring the angles with the arcometer (AA). Two evaluators collected the data using the arcometer, with the rods placed at T1, T12, L1 and L5 spinous processes levels in a way as to permit linear measurements which, with aid of trigonometry, supplied the AA. RESULTS: There was a very strong and significant correlation between AA and CA (r=0.94; p<0.01), with no-significant difference (p=0.32), for the thoracic curvature. There was a strong and significant correlation for the lumbar curvature (r=0.71; p<0.01) between AA and CA, with no-significant difference (p=0.30). There is a very strong correlation between intra-evaluator and inter-evaluator AA. CONCLUSION: It was possible to quantify reliably the thoracic and lumbar curvatures with the arcometer and it can thus be considered valid and reliable and for use in evaluating spinal curvatures in the sagittal plane. PMID- 22045293 TI - Toxicokinetics/toxicodynamics with damage feedback improves risk assessment for tilapia and freshwater clam exposed to arsenic. AB - It has been proposed that irreversible responses of organisms exposed to contaminants are due to a systems-level feedback. Here we tested this hypothesis by reanalyzing the published data on toxicokinetics and survival probability based on a systems-level threshold damage model (TDM) incorporating with a positive damage feedback to explore the steady-state response and dynamic behavior of damage for tilapia and freshwater clam exposed to waterborne arsenic (As). We found that ultrasensitivity appeared in As-tilapia and freshwater clam systems with Hill coefficient n >= 4, indicating that the positive damage feedback mechanism has been triggered. We confirmed that damage can trigger a positive feedback loop that together with As stressor increases irreversibility. This study also showed that TDM with positive feedback gave a much better predictability than that of TDM at As concentrations ranging from 100 to 500 mg l(-1) for freshwater clam, whereas for tilapia, two models had nearly same performance on predictability. We suggested that mortality-time profile derived Hill coefficient could be used as a new risk indicator to assess the survival probability for species exposed to waterborne metals. We anticipated that the proposed toxicokinetics/toxicodynamics with a positive damage feedback may facilitate our understanding and manipulation of complex mechanisms of metal susceptibility among species and improve current risk assessment strategies. PMID- 22045294 TI - Solid-phase synthesis of arginine-based double-tailed cationic lipopeptides: potent nucleic acid carriers. AB - Herein we report a highly-efficient solid-phase strategy for the modular synthesis of 63 double-tailed lipid-peptide conjugates and their application in DNA delivery. PMID- 22045295 TI - Unique and atypical deletions in Prader-Willi syndrome reveal distinct phenotypes. AB - Prader-Willi syndrome (PWS) is a multisystem, contiguous gene disorder caused by an absence of paternally expressed genes within the 15q11.2-q13 region via one of the three main genetic mechanisms: deletion of the paternally inherited 15q11.2 q13 region, maternal uniparental disomy and imprinting defect. The deletion class is typically subdivided into Type 1 and Type 2 based on their proximal breakpoints (BP1-BP3 and BP2-BP3, respectively). Despite PWS being a well characterized genetic disorder the role of the specific genes contributing to various aspects of the phenotype are not well understood. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is a recently developed technique that detects copy number changes and aberrant DNA methylation. In this study, we initially applied MS-MLPA to elucidate the deletion subtypes of 88 subjects. In our cohort, 32 had a Type 1 and 49 had a Type 2 deletion. The remaining seven subjects had unique or atypical deletions that were either smaller (n=5) or larger (n=2) than typically described and were further characterized by array-based comparative genome hybridization. In two subjects both the PWS region (15q11.2) and the newly described 15q13.3 microdeletion syndrome region were deleted. The subjects with a unique or an atypical deletion revealed distinct phenotypic features. In conclusion, unique or atypical deletions were found in ~8% of the deletion subjects with PWS in our cohort. These novel deletions provide further insight into the potential role of several of the genes within the 15q11.2 and the 15q13.3 regions. PMID- 22045296 TI - Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts. AB - Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities. PMID- 22045297 TI - Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus. AB - Keratoconus (KTCN), a non-inflammatory corneal disorder characterized by stromal thinning, represents a major cause of corneal transplantations. Genetic and environmental factors have a role in the etiology of this complex disease. Previously reported linkage analysis revealed that chromosomal region 13q32 is likely to contain causative gene(s) for familial KTCN. Consequently, we have chosen eight positional candidate genes in this region: MBNL1, IPO5, FARP1, RNF113B, STK24, DOCK9, ZIC5 and ZIC2, and sequenced all of them in 51 individuals from Ecuadorian KTCN families and 105 matching controls. The mutation screening identified one mutation and three sequence variants showing 100% segregation under a dominant model with KTCN phenotype in one large Ecuadorian family. These substitutions were found in three different genes: c.2262A>C (p.Gln754His) and c.720+43A>G in DOCK9; c.2377-132A>C in IPO5 and c.1053+29G>C in STK24. PolyPhen analyses predicted that c.2262A>C (Gln754His) is possibly damaging for the protein function and structure. Our results suggest that c.2262A>C (p.Gln754His) mutation in DOCK9 may contribute to the KTCN phenotype in the large KTCN-014 family. PMID- 22045298 TI - Short-term cortical plasticity induced by conditioning pain modulation. AB - To investigate the effects of homotopic and heterotopic conditioning pain modulation (CPM) on short-term cortical plasticity. Glutamate (tonic pain) or isotonic saline (sham) was injected in the upper trapezius (homotopic) and in the thenar (heterotopic) muscles. Intramuscular electrical stimulation was applied to the trapezius at pain threshold intensities, and somatosensory evoked potentials were recorded with 128 channel EEG. Pain ratings were obtained during glutamate and sham pain injection. Short-term cortical plasticity to electrical stimulation was investigated before, during, and after homotopic and heterotopic CPM versus control. Peak latencies at N100, P200, and P300 were extracted and the location/strength of corresponding dipole current sources and multiple dipoles were estimated. Homotopic CPM caused hypoalgesia (P = 0.032, 30.6% compared to baseline) to electrical stimulation. No cortical changes were found for homotopic CPM. A positive correlation at P200 between electrical pain threshold after tonic pain and the z coordinate after tonic pain (P = 0.032) was found for homotopic CPM. For heterotopic CPM, no significant hypoalgesia was found and a dipole shift of the P300 z coordinate (P = 0.001) was found between glutamate versus sham pain (P = 0.009). This generator was located in the cingulate. A positive correlation at P300 between pain ratings to glutamate injection and the x coordinate during tonic pain (P = 0.016) was found for heterotopic CPM. Heterotopic CPM caused short-term cortical plasticity within the cingulate that was correlated to subjective pain ratings. The degree of long-term depressive effect to homotopic CPM was correlated to the change in location of the P200 dipole. PMID- 22045299 TI - Bimanual Fitts' tasks: Kelso, Southard, and Goodman, 1979 revisited. AB - The experiment was designed to replicate and extend to an integrated feedback condition the pattern of movement time results found by Kelso et al. (J Exp Psychol Hum Percept Perform 5:229-238, 1979a, Science 204:1029-1031, 1979b) where the simultaneous movement of one hand to a low ID target and the other to a higher ID target indicated "a tight coordinate coupling between the hands" (p. 229). In the present experiment, a control group was provided feedback that depicted the independent movement of the two limbs under low and higher indexes of difficulty (ID). A Lissajous group was provided integrated feedback in the form of a Lissajous plot. The results indicated a pattern of results for the control and Lissajous groups similar to that found by Kelso et al. for one and two-limb movements to the same difficulty targets. The control group also replicated the finding for two-limb movements to mixed ID tasks. However, the Lissajous group simultaneously produced disparate movement in the mixed target conditions. The results are consistent with recent findings indicating that when provided salient integrated feedback participants can effectively produce disparate movements of the two limbs. PMID- 22045300 TI - Fish oil normalizes plasma glucose levels and improves liver carbohydrate metabolism in rats fed a sucrose-rich diet. AB - A sucrose-rich diet (SRD) induces insulin resistance and dyslipidemia with impaired hepatic glucose production and gluconeogenesis, accompanied by altered post-receptor insulin signaling steps. The aim of this study was to examine the effectiveness of fish oil (FO) to reverse or improve the impaired hepatic glucose metabolism once installed in rats fed 8 months a SRD. In the liver of rats fed SRD in which FO replaced corn-oil during the last 2 months, as dietary fat, several key enzyme activities and metabolites involved in glucose metabolisms (phosphorylation, glycolysis, gluconeogenesis and oxidative and non oxidative glucose pathway) were measured. The protein mass levels of IRS-1 and alphap85 PI 3K at basal conditions were also analyzed. FO improved the altered activities of some enzymes involved in the glycolytic and oxidative pathways observed in the liver of SRD fed rats but was unable to restore the impaired capacity of glucose phosphorylation. Moreover, FO reversed the increase in PEPCK and G-6-Pase and reduced the G-6-Pase/GK ratio. Glycogen concentration and GSa activity returned to levels similar to those observed in the liver of the control-fed rats. Besides, FO did not modify the altered protein mass levels of IRS-1 and alphap85 PI-3K. Finally, dietary FO was effective in reversing or improving the impaired activities of several key enzymes of hepatic carbohydrate metabolism contributing, at least in part, to the normalization of plasma glucose levels in the SRD-fed rats. However, these positive effects of FO were not observed under basal conditions in the early steps of insulin signaling transduction. PMID- 22045302 TI - Hydrostatic fluid pressure in the vestibular organ of the guinea pig. AB - Since inner ear hair cells are mechano-electric transducers the control of hydrostatic pressure in the inner ear is crucial. Most studies analyzing dynamics and regulation of inner ear hydrostatic pressure performed pressure measurements in the cochlea. The present study is the first one reporting about absolute hydrostatic pressure values in the labyrinth. Hydrostatic pressure of the endolymphatic system was recorded in all three semicircular canals. Mean pressure values were 4.06 cmH(2)O +/- 0.61 in the posterior, 3.36 cmH(2)O +/- 0.94 in the anterior and 3.85 cmH(2)O +/- 1.38 in the lateral semicircular canal. Overall hydrostatic pressure in the vestibular organ was 3.76 cmH(2)O +/- 0.36. Endolymphatic hydrostatic pressure in all three semicircular canals is the same (p = 0.310). With regard to known endolymphatic pressure values in the cochlea from past studies vestibular pressure values are comparable to cochlear values. Until now it is not known whether the reuniens duct and the Bast's valve which are the narrowest passages in the endolymphatic system are open or closed. Present data show that most likely the endolymphatic system is a functionally open entity. PMID- 22045301 TI - The Gp78 ubiquitin ligase: probing endoplasmic reticulum complexity. AB - The endoplasmic reticulum (ER) has been classically divided, based on electron microscopy analysis, into parallel ribosome-studded rough ER sheets and a tubular smooth ER network. Recent studies have identified molecular constituents of the ER, the reticulons and DP1, that drive ER tubule formation and whose expression determines expression of ER sheets and tubules and thereby rough and smooth ER. However, segregation of the ER into only two domains remains simplistic and multiple functionally distinct ER domains necessarily exist. In this review, we will discuss the sub-organization of the ER in different domains focusing on the localization and role of the gp78 ubiquitin ligase in the mitochondria-associated smooth ER and on the evidence for a quality control ERAD domain. PMID- 22045303 TI - Pro-inflammatory effects of ochratoxin A on nasal epithelial cells. AB - Eosinophilic chronic rhinosinusitis (ECRS) largely consists of allergic fungal sinusitis, non-allergic fungal rhinosinusitis, aspirin-exacerbated ECRS, and superantigen-induced ECRS. The pathophysiology of ECRS is not completely understood, in particular, the role of mycotoxins remains unknown. The aim of this study was to evaluate the effects of one of the most widespread mycotoxin, ochratoxin A (OTA), on the release of pro-inflammatory cytokines such as interleukin-(IL)-6 and the CXC-chemokine IL-8 from nasal epithelial cell cultures (NEC) of subjects with and without ECRS. NEC (ECRS group: n = 16; controls: n = 7) were stimulated with OTA for 24 h. Protein concentrations of IL-6 and IL-8 levels were measured in NEC supernatants by ELISA prior and 24 h after addition of OTA. Baseline levels in the supernatants of NEC were 183.3 pg/ml for IL-6 and 384.6 pg/ml for IL-8. Stimulation with OTA induced a significant increase of IL-6 (p < 0.001) and IL-8 (p < 0.001) in both NEC of controls and ECRS, respectively. There were no significant differences between controls and ECRS. This is the first study evaluating the effects of a mycotoxin on epithelial airway cells. Our data show that the ubiquitous mycotoxin OTA has a strong pro-inflammatory effect on NEC resulting in the release of IL-6 and IL-8. Mycotoxins may promote inflammation in nasal mucosa. PMID- 22045305 TI - Reconstitution of regulatory T cells after autologous transplantation in multiple myeloma. PMID- 22045306 TI - Intravascular B-cell lymphoma with hypercalcemia as the initial presentation. AB - Intravascular B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma, which is characterized by the growth of lymphoma cells within blood vessel lumina without nodular lesions, and which predominantly affects elderly patients. IVLBCL is characterized by B-symptoms and a variety of systemic symptoms due to focal obstruction of blood flow, but may be difficult to diagnose due to its peculiar intravascular localization and the lack of nodular lesions. While hypercalcemia is one of the complications of various types of cancerous diseases, it has rarely been reported as the first presentation of IVLBCL. In this report, we present the case of a 71-year-old male with IVLBCL who showed hypercalcemia accompanied by elevation of serum parathyroid hormone related protein (PTH-rP) as the initial presentation. Interestingly, immunohistochemical staining revealed that the intravascular lymphoma cells expressed high levels of PTHrP. Six courses of immunochemotherapy, consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), and two courses of high-dose methotrexate induced complete remission (CR) and retained CR for 4 months. We also reviewed other IVBCL cases in which hypercalcemia was the initial presentation. We suggest that IVLBCL, although rare, should be considered as a possible causative in hypercalcemia of unknown underlying disease. PMID- 22045307 TI - Iron-overload myopathy. PMID- 22045308 TI - Update on the pathogenesis and treatment of systemic idiopathic arthritis. AB - PURPOSE OF REVIEW: Systemic juvenile idiopathic arthritis (SJIA) is an inflammatory condition characterized by fever, lymphadenopathy, rash, arthritis, and serositis. Although the ultimate cause of this disorder remains elusive, recent work defining cytokine effector mechanisms has led to a new treatment paradigm for this condition. In this review, we describe the recent immunological reclassification of SJIA as an autoinflammatory disorder as well as detailing the dramatic changes in its treatment. RECENT FINDINGS: SJIA is an autoinflammatory disorder in which defects of innate immune system pathways lead to significant inflammation. Recent studies of the pathophysiology, as well as successful treatment trials, have established interleukin-1beta (IL-1beta) and IL-6 as key cytokines in the pathogenesis of this condition. As a result, their inhibition has become the centerpiece of the current SJIA treatment paradigm. SUMMARY: There has been a major shift away from the traditional treatments of SJIA towards therapeutics that inhibit IL-1beta and IL-6. In fact, the IL-1 blocker anakinra is now regarded as standard of care for SJIA patients with systemic symptoms, while the IL-6 inhibitor tocilizumab shows great potential. Future research holds promise for the development of more efficient cytokine inhibition as well a more comprehensive knowledge of the innate cytokine networks in this disease. PMID- 22045309 TI - Clinical diagnosis and management of attention deficit hyperactivity disorder in preschool children. AB - PURPOSE OF REVIEW: To provide an overview of clinical advances and research findings related to attention deficit hyperactivity disorder (ADHD) in preschool children, with an emphasis on assessment and management. RECENT FINDINGS: The American Academy of Pediatrics has just released new clinical practice guidelines for the diagnosis and management of ADHD. These guidelines are broader in scope, now extending down to preschool children (ages 4 and 5 years). With respect to diagnosis, the American Psychiatric Association has recently proposed modifications to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV); the current draft version of DSM-V includes changes to the diagnosis criteria for ADHD. With respect to treatment of preschool children with ADHD, studies continue to support the efficacy of behavioral interventions. Regarding pharmacotherapy, a large, recently completed, placebo-controlled study of methylphenidate for preschool ADHD identified some age-related medication differences. SUMMARY: ADHD can be reliably diagnosed in preschool children. Behavior therapy remains the recommended first-line treatment approach; pharmacotherapy is sometimes indicated as a treatment adjunct, or, less commonly, a treatment alternative. PMID- 22045311 TI - Osteoarthritis: Crystal-gazing into the pathogenesis of osteoarthritis. PMID- 22045310 TI - Validation of new biomarkers in systemic autoimmune diseases. AB - Biomarkers have an important influence on the clinical decision-making processes involved in diagnosis, assessment of disease activity, allocation of treatment, and determining prognosis. The clinical usefulness of a biomarker is dependant on demonstration of its validity. Ideally, biomarkers should provide information not available from currently available tests and should be tested as they would be used in clinical practice; however, potential biomarkers could be affected by many different clinical or patient variables-such as disease activity, therapeutic intervention, or the presence of comorbidities--and validation studies might not include all the design features that are required to ensure that the biomarker is a true measure of the clinical process it is intended to reflect. In this Review, we appraise studies that have been conducted to validate six promising new biomarkers for diagnosis, disease activity assessment, or prognosis in patients with systemic autoimmune diseases. We discuss the validity of these six biomarkers with particular reference to the features of the studies that lend weight to or distract from their findings. The intent of this discussion is to draw attention to elements of validation study design that should be considered when evaluating the robustness of a biomarker, which differ according to the marker's intended use. PMID- 22045312 TI - Voluntary running exercise prevents beta-cell failure in susceptible islets of the Zucker diabetic fatty rat. AB - Physical activity improves glycemic control in type 2 diabetes (T2D), but its contribution to preserving beta-cell function is uncertain. We evaluated the role of physical activity on beta-cell secretory function and glycerolipid/fatty acid (GL/FA) cycling in male Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rats engaged in voluntary running for 6 wk (ZDF-A). Inactive Zucker lean and ZDF (ZDF I) rats served as controls. ZDF-I rats displayed progressive hyperglycemia with beta-cell failure evidenced by falling insulinemia and reduced insulin secretion to oral glucose. Isolated ZDF-I rat islets showed reduced glucose-stimulated insulin secretion expressed per islet and per islet protein. They were also characterized by loss of the glucose regulation of fatty acid oxidation and GL/FA cycling, reduced mRNA expression of key beta-cell genes, and severe reduction of insulin stores. Physical activity prevented diabetes in ZDF rats through sustaining beta-cell compensation to insulin resistance shown in vivo and in vitro. Surprisingly, ZDF-A islets had persistent defects in fatty acid oxidation, GL/FA cycling, and beta-cell gene expression. ZDF-A islets, however, had preserved islet insulin mRNA and insulin stores compared with ZDF-I rats. Physical activity did not prevent hyperphagia, dyslipidemia, or obesity in ZDF rats. In conclusion, islets of ZDF rats have a susceptibility to failure that is possibly due to altered beta-cell fatty acid metabolism. Depletion of pancreatic islet insulin stores is a major contributor to islet failure in this T2D model, preventable by physical activity. PMID- 22045313 TI - Demonstration of diet-induced decoupling of fatty acid and cholesterol synthesis by combining gene expression array and 2H2O quantification. AB - The liver is a crossroad for metabolism of lipid and carbohydrates, with acetyl CoA serving as an important metabolic intermediate and a precursor for fatty acid and cholesterol biosynthesis pathways. A better understanding of the regulation of these pathways requires an experimental approach that provides both quantitative metabolic flux measurements and mechanistic insight. Under conditions of high carbohydrate availability, excess carbon is converted into free fatty acids and triglyceride for storage, but it is not clear how excessive carbohydrate availability affects cholesterol biosynthesis. To address this, C57BL/6J mice were fed either a low-fat, high-carbohydrate diet or a high-fat, carbohydrate-free diet. At the end of the dietary intervention, the two groups received (2)H(2)O to trace de novo fatty acid and cholesterol synthesis, and livers were collected for gene expression analysis. Expression of lipid and glucose metabolism genes was determined using a custom-designed pathway focused PCR-based gene expression array. The expression analysis showed downregulation of cholesterol biosynthesis genes and upregulation of fatty acid synthesis genes in mice receiving the high-carbohydrate diet compared with the carbohydrate-free diet. In support of these findings, (2)H(2)O tracer data showed that fatty acid synthesis was increased 10-fold and cholesterol synthesis was reduced by 1.6-fold in mice fed the respective diets. In conclusion, by applying gene expression analysis and tracer methodology, we show that fatty acid and cholesterol synthesis are differentially regulated when the carbohydrate intake in mice is altered. PMID- 22045314 TI - Valsartan, independently of AT1 receptor or PPARgamma, suppresses LPS-induced macrophage activation and improves insulin resistance in cocultured adipocytes. AB - Macrophages are integrated into adipose tissues and interact with adipocytes in obese subjects, thereby exacerbating adipose insulin resistance. This study aimed to elucidate the molecular mechanism underlying the insulin-sensitizing effect of the angiotensin II receptor blocker (ARB) valsartan, as demonstrated in clinical studies. Insulin signaling, i.e., insulin receptor substrate-1 and Akt phosphorylations, in 3T3-L1 adipocytes was impaired markedly by treatment with tumor necrosis factor-alpha (TNFalpha) or in the culture medium of lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages, and valsartan had no effects on these impairments. However, in contrast, when cocultured with RAW 264.7 cells using a transwell system, the LPS-induced insulin signaling impairment in 3T3-L1 adipocytes showed almost complete normalization with coaddition of valsartan. Furthermore, valsartan strongly suppressed LPS-induced productions of cytokines such as interleukin (IL)-1beta, IL-6, and TNFalpha with nuclear factor-kappaB activation and c-Jun NH(2)-terminal kinase phosphorylation in RAW 264.7 and primary murine macrophages. Very interestingly, this effect of valsartan was also observed in THP-1 cells treated with angiotensin II type 1 (AT1) siRNA or a peroxisome proliferator-activated receptor-gamma (PPARgamma) antagonist as well as macrophages from AT1a receptor-knockout mice. We conclude that valsartan suppresses the inflammatory response of macrophages, albeit not via PPARgamma or the AT1a receptor. This suppression appears to secondarily improve adipose insulin resistance. PMID- 22045315 TI - Postprandial endothelial function does not differ in women by race: an insulin resistance paradox? AB - Insulin resistance is associated with endothelial dysfunction. Because African American women are more insulin-resistant than white women, it is assumed that African-American women have impaired endothelial function. However, racial differences in postprandial endothelial function have not been examined. In this study, we test the hypothesis that African-American women have impaired postprandial endothelial function compared with white women. Postprandial endothelial function following a breakfast (20% protein, 40% fat, and 40% carbohydrate) was evaluated in 36 (18 African-American women, 18 white women) age and body mass index (BMI)-matched (age: 37 +/- 11 yr; BMI: 30 +/- 6 kg/m(2)) women. Endothelial function, defined by percent change in brachial artery flow mediated dilation (FMD), was measured at 0, 2, 4, and 6 h following a meal. There were no significant differences between the groups in baseline FMD, total body fat, abdominal visceral fat, and fasting levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, or serum estradiol. Although African-American women were less insulin-sensitive [insulin sensitivity index (mean +/- SD): 3.6 +/- 1.5 vs. 5.2 +/- 2.6, P = 0.02], both fasting triglyceride (TG: 56 +/- 37 vs. 97 +/- 49 mg/dl, P = 0.007) and incremental TG area under the curve (AUC(0-6hr): 279 +/- 190 vs. 492 +/- 255 mg.dl(-1).min(-1).10(-2), P = 0.008) were lower in African-American than white women. Breakfast was associated with a significant increase in FMD in whites and African-Americans, and there was no significant difference in postprandial FMD between the groups (P > 0.1 for group * time interactions). Despite being insulin-resistant, postprandial endothelial function in African-American women was comparable to white women. These results imply that insulin sensitivity may not be an important determinant of racial differences in endothelial function. PMID- 22045316 TI - Hyperandrogenism sensitizes mononuclear cells to promote glucose-induced inflammation in lean reproductive-age women. AB - Hyperandrogenism and chronic low-grade inflammation are related in polycystic ovary syndrome (PCOS), but it is unknown whether hyperandrogenemia can activate inflammation. We determined the effect of oral androgen administration on fasting and glucose-stimulated nuclear factor-kappaB (NF-kappaB) activation and expression and related markers of inflammation in mononuclear cells (MNC) of lean reproductive-age women. Sixteen lean, ovulatory reproductive-age women were treated with 130 mg of DHEA or placebo (n = 8 each) for 5 days in a randomized, controlled, double-blind fashion. Nuclear activation of NF-kappaB, p65 and p105 NF-kappaB subunit RNA, TNFalpha and IL-1beta mRNA, and NF-kappaB p65 and inhibitory-kappaB (IkappaB) protein were quantified from MNC obtained while fasting and 2 h after glucose ingestion, before and after DHEA or placebo administration. Before treatment, subjects receiving DHEA or placebo exhibited no differences in androgens or any inflammatory markers while fasting and after glucose ingestion. Compared with placebo, DHEA administration raised levels of testosterone, androstenedione, and DHEA-S, increased the percent change in fasting and glucose-challenged activated NF-kappaB, p65, p105, TNFalpha, and IL 1beta RNA and p65 protein, and decreased the percent change in fasting and glucose-challenged IkappaB protein. We conclude that elevation of circulating androgens to the range observed in PCOS upregulates the NF-kappaB inflammation pathway in lean reproductive-age women. Thus, hyperandrogenemia activates and sensitizes MNC to glucose in this population. PMID- 22045319 TI - Editorial. PMID- 22045317 TI - Epithelial Na+ sodium channels in magnocellular cells of the rat supraoptic and paraventricular nuclei. AB - The epithelial Na+ channels (ENaCs) are present in kidney and contribute to Na+ and water homeostasis. All three ENaC subunits (alpha, beta, and gamma) were demonstrated in the cardiovascular regulatory centers of the rat brain, including the magnocellular neurons (MNCs) in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). However, the functional significance of ENaCs in vasopressin (VP) and oxytocin (OT) synthesizing MNCs is completely unknown. In this study, we show with immunocytochemical double-labeling that the alpha-ENaC is colocalized with either VP or OT in MNCs in the SON and PVN. In addition, parvocellular neurons in the dorsal, ventrolateral, and posterior subregions of the PVN (not immunoreactive to VP or OT) are also immunoreactive for alpha-ENaC. In contrast, immunoreactivity to beta- and gamma-ENaC is colocalized with VP alone within the MNCs. Furthermore, immunoreactivity for a known target for ENaC expression, the mineralcorticoid receptor (MR), is colocalized with both VP and OT in MNCs. Using single-cell RT-PCR, we detected mRNA for all three ENaC subunits and MR in cDNA libraries derived from single MNCs. In whole cell voltage clamp recordings, application of the ENaC blocker benzamil reversibly reduced a steady-state inward current and decreased cell membrane conductance approximately twofold. Finally, benzamil caused membrane hyperpolarization in a majority of VP and about one-half of OT neurons in both spontaneously firing and quiet cells. These results strongly suggest the presence of functional ENaCs that may affect the firing patterns of MNCs, which ultimately control the secretion of VP and OT. PMID- 22045320 TI - Initial motor symptoms of Parkinson disease. AB - Parkinson disease (PD) is characterized by a wide variety of motor and nonmotor symptoms. Although recently nonmotor symptoms have gained considerable relevance and interest, especially in advanced stages, motor symptoms define the main core of PD and are essential for clinical diagnosis. In this article, we review the characteristics, presentation, and evolution of motor symptoms in early PD. PMID- 22045321 TI - Dopamine receptors, motor responses, and dopaminergic agonists. AB - Dopamine receptors are widely distributed within the central nervous system with its highest expression in the striatum. Two different families of dopamine receptors have been identified. The D1 family comprises D1 and D5 receptors, whereas D2, D3, and D4 receptors form the D2 family. These 2 families mediate different behavior patterns that are linked to activation of specific transduction pathways. The functional relevance of dopamine receptors derives from the reduced dopamine content found in the striatum of Parkinson disease (PD) patients and the ability of dopamine and dopamine receptors to reverse the motor deficits exhibited by PD patients. During the last 2 decades dopamine receptor agonists have been used either in de novo PD patients to prevent the appearance of dyskinesias or in PD patients with motor fluctuations to reduce the number of daily "off" hours. It seems that all dopamine receptors agonists produce similar motor responses and adverse effects, but data comparing their effectiveness in the treatment of PD are not available. In this article we summarize the main characteristics of dopamine receptors, their structure, their signaling pathways, and the responses mediated by their independent activation. Here is also described the therapeutic value of the different dopamine receptor agonists in the treatment of PD. PMID- 22045322 TI - Assessment of Parkinson disease: what do we need to show neuroprotection? AB - To date, no pharmacological agent has convincingly demonstrated the ability to slow the progression of Parkinson disease (PD). The development of treatments that slow down the progressive degeneration of the nigrostriatal dopaminergic system (true neuroprotection), which is ultimately responsible for the patients' functional decline, has become one of the basic goals of PD research. In this review, we have attempted to analyze the role of different methods that measure PD severity (basically, clinical scales, timed tests, and neuroimaging techniques) in the evaluation of the "neuroprotection" provided by different types of treatment for the disease, on the basis of clinical evidence. PMID- 22045323 TI - Continuous dopaminergic stimulation: clinical aspects and experimental bases. AB - In patients with Parkinson disease, pulsatile administration of dopaminergic drugs is associated with motor fluctuations and dyskinesias. By contrast, treatments that provide more continuous dopaminergic stimulation are associated with less intense motor complications. This can be achieved by using drugs with longer half-lives, delayed release formulations, and routes of administration that permit continuous delivery. The mechanisms by which different modes of dopaminergic treatment (pulsatile or continuous) determine the motor response are not fully understood. However, the use of experimental models of parkinsonism has helped understand the motor complications associated with pulsatile dopamine replacement. These studies have provided important insights into the biochemical and molecular changes in the basal ganglia in response to continuous stimulation. In addition, these models have facilitated the development of new treatments that may stabilize the motor response and the biochemical alterations in the basal ganglia to provide more efficient forms of continuous dopaminergic stimulation in patients with Parkinson disease. PMID- 22045324 TI - Sleep disorders in Parkinson disease. AB - Sleep is affected in a large number of patients with Parkinson disease. The mechanisms by which this occurs and the different types of sleep disorders that a patient with Parkinson disease may suffer (insufficient or fragmented sleep, persistent excessive daytime sleepiness, sudden onset of sleep episodes, obstructive sleep apnea (OSA), rapid eye movement sleep behavior disorder, and restless legs syndrome) will be reviewed in this study, as well as their relationship with the dopaminergic system. Finally, the most effective treatments will be proposed. PMID- 22045325 TI - Treatment of Parkinson disease, time and dosage: "does simple dosage facilitate compliance and therapeutic goals?". AB - Current available treatment for Parkinson disease has many drawbacks: single action on the nigrostriatal pathway, no halt of disease progression, pulsatile dopaminergic stimulation, complex treatment regimens, and motor complications. Compliance with treatment may be irregular in a variable number of patients. Factors such as age, education, complexity of posology, stage of disease, disease comprehension, cognitive function, or family support significantly influence compliance either in a positive or negative way. The consequences of noncompliance include withdrawal symptoms, increase in number of admissions, or, in severe cases, hyperthermia syndrome secondary to levodopa deficit in the case of infradose. In situations of overdose, dyskinesia or psychiatric complications may arise. The ideal treatment should have the potency of levodopa but not its side effects, act on striatal D2 receptors in a continuous way with a single dose and have low potential of addiction. Thus far, simple regimens are only applicable in early stages. PMID- 22045326 TI - Exercise and physical therapy in early management of Parkinson disease. AB - Experimental research has produced evidence in recent years underlying the beneficial effects that exercise can have in preventing and deceleration of the development of Parkinson disease. These beneficial effects are exerted through various mechanisms such as neuroprotection, neurotransmission, plasticity, neurogenesis, homeostasis, and neurotrophic factors. Studies on clinical application at an early stage are still scarce, although some results are encouraging. There are still many questions to determine the most suitable type of exercise (forced/voluntary), the time of its implementation, the duration, and the combination of strategies. Nonconventional therapies can play an important role in addition to exercise, and are so numerous that they could be adapted to the circumstances of patients, although there is no evidence to date that they could have a neuroprotective effect. PMID- 22045327 TI - Neuroprotective role of dopamine agonists: evidence from animal models and clinical studies. AB - Parkinson disease is a progressive neurodegenerative disease that affects, among other neurotransmitter systems, the nigrostriatal dopaminergic projection. Palliative treatment with levodopa and/or dopamine agonists improves motor symptoms even though patients continue to get clinically worse by the neurodegenerative process that continues to act as the major factor of physiological aging. Studies (in vitro and in vivo) with experimental models have shown that dopamine agonists have neuroprotective effects, directly or indirectly mediated by their ability to stabilize mitochondria, antioxidant effects, synthesis of growth factors, stabilization of the ubiquitin-proteasome system, activation of autophagy, antiapoptotic induction of Bcl2 family, or enhancement of neurogenesis (proliferation and migration) in the subventricular zone. Clinical studies have not completely confirmed these effects. Analysis in better characterized groups of patients with similar clinical symptoms, identical treatments, and the same evolution time are required. Technological advances which enable the learning of the etiology and the pathogenesis (genetic and environmental) of the disease, together with clinical assessment methods, bring hope to the development of new molecules in the symptomatic treatment of Parkinson disease. These molecules must display neuroprotective potential (prophylactic and/or therapeutic) which must be able to maintain the brain's physiological function and to modify or slow the natural course of the disease. PMID- 22045328 TI - Nonmotor disorders and their correlation with dopamine: can they be treated by currently available methods? AB - Many of the nonmotor symptoms in Parkinson disease have a dopaminergic basis, whether the result of dopaminergic degeneration or as a result of dopaminergic treatment. In the latter case, the symptoms may be genuine side effects of drugs (hypotension, pathologic gambling, etc.) or they may be secondary either to the pathoplastic effect they have on the natural course of the disease (nonmotor fluctuations) or to the lack of dopamine (apathy, depression, dopamine withdrawal syndrome, etc.). In all these cases, dopaminergic treatment can be helpful. However, many other nonmotor (and motor) symptoms will have no correlation with dopamine; therefore, they require different treatments, very often with little efficacy, as in apathy or cognitive decline. PMID- 22045329 TI - Triple-negative breast cancers and the human mammary epithelial cell hierarchy. AB - Triple-negative breast cancers (TNBCs) are a diverse set of aggressive breast cancers that lack expression of estrogen and progesterone receptors, and lack HER2 amplification. Gene expression profiling has revealed distinct subsets of TNBCs, each characterized by unique patterns of gene expression and genomic changes. Comparative analysis of gene expression profiles also suggests that the different subclasses of TNBCs may arise from specific sets of mammary progenitor cell populations. In this article, recent data regarding characterization of a human mammary stem cell hierarchy and its relationship to the pathogenesis of subsets of triple-negative breast cancers will be reviewed. PMID- 22045330 TI - Continuous microfluidic DNA and protein trapping and concentration by balancing transverse electrokinetic forces. AB - Sample pre-concentration can be a critical element to improve sensitivity of integrated microchip assays. In this work a converging Y-inlet microfluidic channel with integrated coplanar electrodes was used to investigate transverse DNA and protein migration under uniform direct current (DC) electric fields to assess the ability to concentrate a sample prior to other enzymatic modifications or capillary electrophoretic separations. Employing a pressure-driven flow to perfuse the microchannel, negatively charged samples diluted in low and high ionic strength buffers were co-infused with a receiving buffer of the same ionic strength into a main daughter channel. Experimental results demonstrated that, depending of the buffer selection, different DNA migration and accumulation dynamics were seen. Charged analytes could traverse the channel width and accumulate at the positive bias electrode in a low electroosmotic mobility, high electrophoretic mobility, high ionic strength buffer or migrated towards an equilibrium position within the channel in a high electroosmotic mobility, high electrophoretic mobility, low ionic strength buffer. The various migration behaviours are the result of a balance between the electrophoretic force and a drag force induced by a recirculating electroosmotic flow generated across the channel width due to the bounding walls. Under continuous flow conditions, DNA samples were concentrated several-fold by balancing these transverse electrokinetic forces. The electrokinetic trapping technique presented here is a simple technique which could be expanded to concentrate or separate other analytes as a preconditioning step for downstream processes. PMID- 22045331 TI - Effects of pH and low molecular weight organic acids on competitive adsorption and desorption of cadmium and lead in paddy soils. AB - The bioavailability and ultimate fate of heavy metals in the environment are controlled by adsorption-desorption process. Batch equilibrium experiments were performed to assess the effects of pH and low molecular weight organic acids (LMWOAs) on competitive adsorption and desorption of cadmium and lead in paddy soils from China. The results indicated that both soils exhibited greater sorption capacity for lead (Pb) (1.37-1.61-fold) than cadmium (Cd) as estimated by the maximum sorption parameter (Q) from the Langmuir equation. The Langmuir bonding energy coefficient (b) and distribution coefficient (K (d)) were greater for Pb than for Cd, furthermore, b (binary) and K (d) (single) were greater than b (single) and K (d binary), indicating that competition for sorption sites promote the retention of both metals on more specific sorption sites. Both Cd and Pb desorption as a function of solution pH was characteristic of "S" pattern. The presence of LMWOAs inhibited Cd or Pb desorption at the low concentrations (<=0.1 mmol L(-1)) but promoted Cd and Pb desorption at higher concentrations (>=0.5 mmol L(-1) for citric acid and >=1 mmol L(-1) for malic and oxalic acid). The two paddy soils had a greater d (Cd) than d (Pb) in the presence of LMWOAs, indicating that Cd desorption was more affected by the presence of LMWOAs in binary metal system. PMID- 22045332 TI - Mitochondrial permeability transition induced by different concentrations of zinc. AB - Zinc is one of the required trace elements in animals, and it serves an important role in biological systems. However, high levels of zinc are poisonous to organisms. So far, there exist conflicting reports about zinc ions-induced mitochondrial permeability transition (MPT). We analyzed the effects of Zn2+ on MPT by monitoring mitochondrial swelling with the ultraviolet-visible light absorption spectrum, characterizing the fluidity of the membrane with fluorescence anisotropy, detecting the transmembrane potential (Deltapsi) with fluorescence intensity, and observing mitochondrial ultrastructure with transmission electron microscopy. Data reveal that low concentrations of zinc ions can trigger MPT while high levels of zinc ions cannot, which implies that zinc ions' toxicity cannot be the result of a single simple mechanism. PMID- 22045333 TI - Cyclophilin 40 facilitates HSP90-mediated RISC assembly in plants. AB - Posttranscriptional gene silencing is mediated by RNA-induced silencing complexes (RISCs) that contain AGO proteins and single-stranded small RNAs. The assembly of plant AGO1-containing RISCs depends on the molecular chaperone HSP90. Here, we demonstrate that cyclophilin 40 (CYP40), protein phosphatase 5 (PP5), and several other proteins with the tetratricopeptide repeat (TPR) domain associates with AGO1 in an HSP90-dependent manner in extracts of evacuolated tobacco protoplasts (BYL). Intriguingly, CYP40, but not the other TPR proteins, could form a complex with small RNA duplex-bound AGO1. Moreover, CYP40 that was synthesized by in vitro translation using BYL uniquely facilitated binding of small RNA duplexes to AGO1, and as a result, increased the amount of mature RISCs that could cleave target RNAs. CYP40 was not contained in mature RISCs, indicating that the association is transient. Addition of PP5 or cyclophilin-binding drug cyclosporine A prevented the association of endogenous CYP40 with HSP90-AGO1 complex and inhibited RISC assembly. These results suggest that a complex of AGO1, HSP90, CYP40, and a small RNA duplex is a key intermediate of RISC assembly in plants. PMID- 22045334 TI - Ablation of Smurf2 reveals an inhibition in TGF-beta signalling through multiple mono-ubiquitination of Smad3. AB - TGF-beta signalling is regulated by post-translational modifications of Smad proteins to translate quantitative difference in ligand concentration into proportional transcriptional output. Previous studies in cell culture systems suggested that Smad ubiquitination regulatory factors (Smurfs) act in this regulation by targeting Smads for proteasomal degradation, but whether this mechanism operates under physiological conditions is not clear. Here, we generated mice harbouring a target-disrupted Smurf2 allele. Using primary mouse embryonic fibroblasts and dermal fibroblasts, we show that TGF-beta-mediated, Smad-dependent transcriptional responses are elevated in the absence of Smurf2. Instead of promoting poly-ubiquitination and degradation, we show that Smurf2 actually induces multiple mono-ubiquitination of Smad3 in vivo. Phosphorylation of T179, immediately upstream of the Smad3 PY motif, enhances Smurf2 and Smad3 interaction and Smad3 ubiquitination. We have mapped Smurf2-induced Smad3 ubiquitination sites to lysine residues at the MH2 domain, and demonstrate that Smad3 ubiquitination inhibits the formation of Smad3 complexes. Thus, our data support a model in which Smurf2 negatively regulates TGF-beta signalling by attenuating the activity of Smad3 rather than promoting its degradation. PMID- 22045335 TI - Multiple Cdt1 molecules act at each origin to load replication-competent Mcm2-7 helicases. AB - Eukaryotic origins of replication are selected by loading a head-to-head double hexamer of the Mcm2-7 replicative helicase around origin DNA. Cdt1 plays an essential but transient role during this event; however, its mechanism of action is unknown. Through analysis of Cdt1 mutations, we demonstrate that Cdt1 performs multiple functions during helicase loading. The C-terminus of Cdt1 binds Mcm2-7, and this interaction is required for efficient origin recruitment of both proteins. We show that origin recognition complex (ORC) and Cdc6 recruit multiple Cdt1 molecules to the origin during helicase loading, and disruption of this multi-Cdt1 intermediate prevents helicase loading. Although dispensable for loading Mcm2-7 double hexamers that are topologically linked to DNA, the essential N-terminal domain of Cdt1 is required to load Mcm2-7 complexes that are competent for association with the Cdc45 and GINS helicase-activating proteins and replication initiation. Our data support a model in which origin-bound ORC and Cdc6 recruit two Cdt1 molecules to initiate double-hexamer formation prior to helicase loading and demonstrate that Cdt1 influences the replication competence of loaded Mcm2-7 helicases. PMID- 22045336 TI - Symmetry-free cryo-EM structures of the chaperonin TRiC along its ATPase-driven conformational cycle. AB - The eukaryotic group II chaperonin TRiC/CCT is a 16-subunit complex with eight distinct but similar subunits arranged in two stacked rings. Substrate folding inside the central chamber is triggered by ATP hydrolysis. We present five cryo EM structures of TRiC in apo and nucleotide-induced states without imposing symmetry during the 3D reconstruction. These structures reveal the intra- and inter-ring subunit interaction pattern changes during the ATPase cycle. In the apo state, the subunit arrangement in each ring is highly asymmetric, whereas all nucleotide-containing states tend to be more symmetrical. We identify and structurally characterize an one-ring closed intermediate induced by ATP hydrolysis wherein the closed TRiC ring exhibits an observable chamber expansion. This likely represents the physiological substrate folding state. Our structural results suggest mechanisms for inter-ring-negative cooperativity, intra-ring positive cooperativity, and protein-folding chamber closure of TRiC. Intriguingly, these mechanisms are different from other group I and II chaperonins despite their similar architecture. PMID- 22045337 TI - LRPPRC is necessary for polyadenylation and coordination of translation of mitochondrial mRNAs. AB - Regulation of mtDNA expression is critical for maintaining cellular energy homeostasis and may, in principle, occur at many different levels. The leucine rich pentatricopeptide repeat containing (LRPPRC) protein regulates mitochondrial mRNA stability and an amino-acid substitution of this protein causes the French Canadian type of Leigh syndrome (LSFC), a neurodegenerative disorder characterized by complex IV deficiency. We have generated conditional Lrpprc knockout mice and show here that the gene is essential for embryonic development. Tissue-specific disruption of Lrpprc in heart causes mitochondrial cardiomyopathy with drastic reduction in steady-state levels of most mitochondrial mRNAs. LRPPRC forms an RNA-dependent protein complex that is necessary for maintaining a pool of non-translated mRNAs in mammalian mitochondria. Loss of LRPPRC does not only decrease mRNA stability, but also leads to loss of mRNA polyadenylation and the appearance of aberrant mitochondrial translation. The translation pattern without the presence of LRPPRC is misregulated with excessive translation of some transcripts and no translation of others. Our findings point to the existence of an elaborate machinery that regulates mammalian mtDNA expression at the post transcriptional level. PMID- 22045338 TI - Palmitoylated TMX and calnexin target to the mitochondria-associated membrane. AB - The mitochondria-associated membrane (MAM) is a domain of the endoplasmic reticulum (ER) that mediates the exchange of ions, lipids and metabolites between the ER and mitochondria. ER chaperones and oxidoreductases are critical components of the MAM. However, the localization motifs and mechanisms for most MAM proteins have remained elusive. Using two highly related ER oxidoreductases as a model system, we now show that palmitoylation enriches ER-localized proteins on the MAM. We demonstrate that palmitoylation of cysteine residue(s) adjacent to the membrane-spanning domain promotes MAM enrichment of the transmembrane thioredoxin family protein TMX. In addition to TMX, our results also show that calnexin shuttles between the rough ER and the MAM depending on its palmitoylation status. Mutation of the TMX and calnexin palmitoylation sites and chemical interference with palmitoylation disrupt their MAM enrichment. Since ER localized heme oxygenase-1, but not cytosolic GRP75 require palmitoylation to reside on the MAM, our findings identify palmitoylation as key for MAM enrichment of ER membrane proteins. PMID- 22045339 TI - Unusual visible luminescence of aluminium polyoxocations in aqueous solution. AB - Identification of aluminium polyoxocations, MO(4)Al(12)(OH)(24)(H(2)O)(12)(7/8+) (M = Al, Ga and Ge) (K-MAl(12)) and Al(30)O(8)(OH)(56)(H(2)O)(26)(18+) (Al(30)), by their luminescence is reported. The fluorescence behavior of K-Al(13) has been found to differ with different metal ions and anions, implying a new discovery of a potential ion sensor. PMID- 22045340 TI - Mood disorders in the light of genes, comorbidity and contemporary treatment. PMID- 22045341 TI - Clinical, virologic, and immunologic correlates of HIV-1 intraclade B dual infection among men who have sex with men. AB - OBJECTIVE: To investigate the susceptibilities to and consequences of HIV-1 dual infection. DESIGN: We compared clinical, virologic, and immunologic factors between participants who were dually infected with HIV-1 subtype B and monoinfected controls who were matched by ongoing HIV risk factor. METHODS: The viral load and CD4 progressions of dually and singly infected participant groups were compared with linear mixed-effects models, and individual dynamics before and after superinfection were assessed with a structural change test (Chow test). Recombination breakpoint analysis (GARD), HLA frequency analysis, and cytotoxic T lymphocyte (CTL) epitope mapping were also performed (HIV LANL Database). RESULTS: The viral loads of dually infected participants increased more over 3 years of follow-up than the viral loads of monoinfected controls, whereas CD4 progressions of the two groups did not differ. Viral escape from CTL responses following superinfection was observed in two participants whose superinfecting strain completely replaced the initial strain. This pattern was not seen among participants whose superinfecting virus persisted in a recombinant form with the initial virus or was only detected transiently. Several HLA types were over represented in dually infected participants as compared to monoinfected controls. CONCLUSIONS: These results identify potential factors for dual infection susceptibility and further define its clinical consequences. PMID- 22045342 TI - Level of double negative T cells, which produce TGF-beta and IL-10, predicts CD8 T-cell activation in primary HIV-1 infection. AB - OBJECTIVE: Persistent immune activation plays a central role in the pathogenesis of HIV disease. Besides natural regulatory T cells (nTregs), 'double negative' T cells shown to exhibit regulatory properties could be involved in the control of harmful immune activation. The aim of this study was to analyze, in patients with primary HIV infection (PHI), the relationship between CD4(+)CD25(+)CD127(low)FoxP3(+) nTregs or CD3(+)CD4(-)CD8(-) double negative T cells and systemic immune activation. DESIGN: A prospective longitudinal study of patients with early PHI. METHODS: Twenty-five patients were included. Relationships between frequency of Treg subsets and T-cell activation, assessed on fresh peripheral blood mononuclear cells, were analyzed using nonparametric tests. Cytokine production by double negative T cells was assessed following anti CD3/anti-CD28 stimulation. RESULTS: No relationship was found between T-cell activation and frequencies of nTregs. In contrast, a strong negative relationship was found at baseline between the proportion of double negative T cells and the proportion of activated CD8 T cells coexpressing CD38 and HLA-DR (P = 0.005) or expressing Ki-67 (P = 0.002). In addition, the frequency of double negative T cells at baseline negatively correlated with the frequency of HLA DR(+)CD38(+)CD8(+) T cells at month 6, defining the immune activation set point (P = 0.031). High proportions of stimulated double negative T cells were found to produce the immunosuppressive cytokines transforming growth factor-beta1 and/or IL-10. CONCLUSION: The proportion of double negative T cells at baseline was found to be predictive of the immune activation set point. Our data strongly suggest that double negative T cells may control immune activation in PHI. This effect might be mediated through the production of TGF-beta1/IL-10 known to downmodulate immune activation. PMID- 22045343 TI - A glycomimetic compound inhibits DC-SIGN-mediated HIV infection in cellular and cervical explant models. AB - OBJECTIVE: Dendritic cell-specific intercellular adhesion molecule (ICAM)-3 grabbing nonintegrin (DC-SIGN) participates in the initial stages of sexually transmitted HIV-1 infection by recognizing highly mannosylated structures presented in multiple copies on HIV-1 gp120 and promoting virus dissemination. Inhibition of HIV interaction with DC-SIGN thus represents a potential therapeutic approach for viral entry inhibition at the mucosal level. DESIGN: Herein we evaluate the efficacy in inhibiting HIV-1 infection and the potential toxicity of a multimeric glycomimetic DC-SIGN ligand (Dendron 12). METHODS: The ability of Dendron 12 to block HIV-1 infection was assessed in cellular and human cervical explant models. Selectivity of Dendron 12 towards DC-SIGN and langerin was evaluated by surface plasmon resonance studies. beta chemokine production following stimulation with Dendron 12 was also analyzed. Toxicity of the compound was evaluated in cellular and tissue models. RESULTS: Dendron 12 averted HIV-1 trans infection of CD4(+) T lymphocytes in presence of elevated viral loads and prevented HIV-1 infection of human cervical tissues, under conditions mimicking compromised epithelial integrity, by multiple clades of R5 and X4 tropic viruses. Treatment with Dendron 12 did not interfere with the activity of langerin and also significantly elicited the production of the beta chemokines MIP-1alpha, MIP 1beta and RANTES. CONCLUSION: Dendron 12 thus inhibits HIV-1 infection by competition with binding of HIV to DC-SIGN and stimulation of beta-chemokine production. Dendron 12 represents a promising lead compound for the development of anti-HIV topical microbicides. PMID- 22045344 TI - Proximate context of gender-unequal norms and women's HIV risk in sub-Saharan Africa. AB - OBJECTIVE: To determine whether the proximate context of gender-unequal norms about violence against women undermines women's ability to negotiate condom use in sexual relationships. DESIGN: Secondary analysis of cross-sectional data pooled from 22 Demographic and Health Surveys conducted in sub-Saharan Africa. METHODS: Each of the 22 surveys employed a multistage stratified design with probabilistic sampling and was designed to be nationally representative of reproductive-age women. The outcome was self-reported condom use at last sexual intercourse. The primary explanatory variable of interest was a scale consisting of five questions about whether the respondent agreed with the appropriateness of wife beating under five different scenarios. To measure the proximate context of norms about violence against women, this scale was aggregated to the level of the primary sampling unit. We fit logistic regression models with cluster-correlated robust standard errors and adjustment for country-level fixed effects and sociodemographic characteristics. RESULTS: Our analysis sample included data from 198,806 sexually active women living in 22 sub-Saharan African countries. The wife-beating scale was internally consistent (Cronbach's alpha = 0.84), and factor analysis confirmed the presence of a single factor. Condom use was associated with gender-unequal contextual norms about violence against women (adjusted odds ratio = 0.88; 95% confidence interval, 0.85-0.92; P < 0.001). The estimated association was robust to adjustment for sociodemographic characteristics and several sensitivity analyses. CONCLUSIONS: The proximate context of gender-unequal norms about violence against women is associated with lack of condom use among women in sub-Saharan Africa. PMID- 22045345 TI - Apparent declining efficacy in randomized trials: examples of the Thai RV144 HIV vaccine and South African CAPRISA 004 microbicide trials. PMID- 22045346 TI - Efficacy of bipolar release in neglected congenital muscular torticollis patients. AB - Surgical correction of the congenital muscular torticollis (CMT) is recommended for patients with unsuccessful conservative treatment. The aim of this study is to evaluate the efficacy of surgical release of congenital muscular torticollis in neglected cases. We retrospectively evaluated the data of our patients in terms of age, sex, clinical presentation, localization of the lesion, diagnostic tests, and additional abnormalities. The age at operation ranged from 6 to 23 years. Complete muscular release as determined by pre-operative and postoperative range of motion measurements was achieved in all of the patients by bipolar release. In this study, neck motion and head tilt showed marked improvement with surgical treatment in cases with CMT who were admitted to the hospital lately. Congenital muscular torticollis patients can benefit from surgical intervention above the age of 5. Bipolar release is an adequate and complication-free method. PMID- 22045347 TI - Nocturnal asthma. AB - PURPOSE OF REVIEW: The aim is to review pathophysiological mechanisms and treatment of nocturnal asthma. RECENT FINDINGS: Physiologic changes accompanying sleep, as well as the nocturnal phase of circadian rhythms, may have an adverse effect on asthma control. Chronotherapeutic principles, which consider circadian variation in relevant biologic rhythms, may improve asthma outcomes. Administration of long-acting bronchodilators and inhaled corticosteroids which achieve maximum efficacy at night may improve nocturnal asthma. Comorbid conditions that may contribute to nocturnal asthma should be considered. The prevalence of obstructive sleep apnea is greater in a cohort of patients with severe asthma than in moderate asthma and in BMI and age matched nonasthmatic controls, suggesting a link between these diseases. A large trial concluded that esomeprazole did not improve asthma control even with comorbid acid reflux, questioning the importance of acid reflux in asthma. The role of polymorphisms of the beta2-adrenergic receptor and their relationship with nocturnal asthma remain controversial. SUMMARY: Sleep is a time of vulnerability to respiratory compromise, especially in asthma patients experiencing nocturnal exacerbations. This asthma phenotype is associated with poorer control, reduced sleep quality, daytime somnolence and increased morbidity and mortality. Nocturnal asthma is a common but under-recognized problem. PMID- 22045348 TI - Inflammatory biomarkers in severe asthma. AB - PURPOSE OF REVIEW: Severe asthma remains a condition in search of deeper understanding and of newer effective therapies. Risk factors for developing severe asthma, phenotyping of disease, characterizing the inflammatory response and understanding of poor therapeutic responses to corticosteroids are important areas of research. The development of biomarkers for phenotypic diagnosis and prognostic reasons is important. RECENT FINDINGS: Severe asthma has been defined as asthma that does not respond adequately to asthma medications, particularly corticosteroids, with continuing loss of control of asthma and future risk of exacerbations and side effects from corticosteroid therapy. This is a heterogeneous condition and cluster analyses have yielded phenotypes on the basis of age of onset of disease, sex, lung function, atopy and questionnaire data. Use of sputum eosinophil counts has further defined a group with persistent eosinophilic inflammation despite corticosteroid therapy, and a noneosinophilic group with uncontrolled asthma. SUMMARY: Use of a single biomarker provides value in phenotyping and in predicting response to treatment but many more biomarkers such as those derived from -omic approaches remain to be used in the analysis. A systems biology approach to finding novel biomarkers is the way forward to stratify severe asthma so that appropriate and distinct therapies can be selected for each subtype. PMID- 22045349 TI - Complications associated with urinary diversion. AB - Radical cystectomy (RC) with subsequent urinary diversion has been assessed to be the most difficult surgical procedure in the field of urology. No randomized trials have been performed to compare the outcomes of noncontinent conduit diversion, neobladder construction and continent cutaneous diversion. Almost all studies are of level 3 evidence, meaning the recommendations given in this Review are of grade C only. Until recently, significant disparity in the quality of surgical complication reporting, as well as the lack of universally accepted reporting guidelines, definitions and grading systems, have made it impossible to compare the surgical morbidity and outcomes of RC. There is a clear case for the standardized reporting of complications. The Clavien system is a straightforward and validated instrument that has already been successfully adopted by several urological centers. Surgical morbidity following RC is significant and, when strict reporting guidelines are incorporated, much higher than previously published. Complications can occur up to 20 years after surgery, emphasizing the need for more long-term studies to determine the full morbidity spectrum. In general, renal function after construction of continent detubularized reservoirs compares favorably with ileal conduit diversion, although the literature is insufficient to recommend one over the other. The challenge of optimum care for elderly patients with comorbidities is best mastered at a high-volume hospital by a high-volume surgeon. PMID- 22045350 TI - Biomarkers for ovarian cancer: new technologies and targets to address persistently unmet needs. PMID- 22045351 TI - FDG-PET/CT as a molecular biomarker in ovarian cancer. AB - In the clinical setting the vast majority of positron emission tomography (PET) procedures use the glucose analogue F-18 fluorodeoxyglucose (FDG) to visualize the increased glucose consumption of malignant lesions. Co-registered PET/CT has improved the diagnostic accuracy compared to either imaging procedure alone, particularly in ovarian cancer. FDG-PET/CT demonstrates primary malignant ovarian tumors; however, it is often unable to accurately differentiate between benign and malignant pelvic masses and to visualize borderline ovarian tumors. FDG PET/CT has a suggested role for staging, by improving treatment planning in individual cases, but it is particularly helpful in the setting of disease recurrence when CA125 tumor marker levels are rising and conventional imaging (CT or MR) is inconclusive or negative. The aim of this review is to demonstrate the value of FDG-PET-CT in diagnosis and management of patients with ovarian malignancies, outlining its advantages and limitations. PMID- 22045352 TI - Screening for ovarian cancer: old tools, new lessons. AB - The early detection of ovarian cancer represents a clinical objective with an enormous potential for a meaningful improvement in our ability to treat and cure afflicted patients. The magnitude of this potential is matched by the challenges associated with attaining it. In addition to the well noted aspects of ovarian cancer which have thus far precluded the development a effective screening strategies, recent work regarding the differential pathogenesis and origins of the various histological subtypes of epithelial ovarian cancer have further revealed the challenges ahead. These findings are reviewed here with a particular focus on reports describing the early development of high-grade serous carcinomas, the most prevalent and aggressive disease subtype. The unique set of difficulties associated with the early detection of these tumors is discussed in depth. An update on findings stemming from several large randomized screening trials is provided. While the current state of ovarian cancer screening remains characterized by unmet needs, the ongoing evaluation of those needs is providing a strong basis for future advancement. This advancement will rely upon the refined application of currently available diagnostic tools based on lessons well learned. PMID- 22045353 TI - Autoantibodies as biomarkers for ovarian cancer. AB - Ovarian cancer (OVCA) has the highest mortality of all gynecologic cancers. The poor survival rate is due to the lack of diagnostic screening tests and high incidence of recurrence in OVCA patients resistant to chemotherapy that leads to a more aggressive form of the disease. Therefore, a search for biomarkers holds great promise not only for early detection of OVCA at presymptomatic stage and for monitoring the course of the disease during the first-line chemotherapy treatment but also for identifying those women whose disease is likely to recur. Research efforts have sought to unravel the complexity of the tumor specific proteome by profiling immune responses generated against tumor associated antigens (TAAs) using multianalyte-based analytical discovery platforms readily adaptable to clinical diagnostic screening tests. The occurrence of tumor specific autoantibodies directed to respective TAAs can be observed before the development of clinical symptoms. Evaluation of the level of tumor autoantibodies during the time of tumor debulking followed by first-line chemotherapy for the prediction of early recurrence as well as their correlation with other clinical parameters to evaluate their prognostic value has been conducted in various clinical studies. The anti-tumor immune response against OVCA is the ultimate key to the development of multiple immune-based therapeutic strategies that have been proposed and tested in different clinical trials that may have beneficial impact on the disease outcome in OVCA patients. PMID- 22045354 TI - The role of chromatin, microRNAs, and tumor stem cells in ovarian cancer. AB - SUMMARY: The term "epigenetics" refers to DNA sequence-independent events that regulate gene expression, including DNA methylation, modifications to histone proteins, and microRNA-associated post-transcriptional control of protein translation. Epigenetic aberrations are now considered a defining characteristic of numerous human pathologies, including cancer. However, in contrast to DNA sequence mutations, many oncogenic epigenetic modifications are potentially reversible, with studies now showing numerous tumor cell types to possess remarkable phenotypic "plasticity," strongly supporting possible reversion of their malignant status. The "epigenome" of one such malignancy, ovarian cancer, has now been studied in depth, with specific epigenetic alterations correlated with tumor initiation, progression, metastasis, and therapy resistance. Ovarian cancer is the most lethal malignancy of the female reproductive tract, largely due to lack or diagnoses of early-stage disease and the eventual develoment of drug resistance; thus, reliable early detection biomarkers and alternative therapies are urgently needed. In this chapter, we discuss the epigenetics of ovarian cancer, including its likely role in the establishment of "cancer stem cells," i.e., highly tumorigenic progenitor cells believed to be largely or solely responsible for the propagation of malignant, chemotherapy-resistant and metastatic disease. Improved understanding of these gene-regulatory phenomena could likely result in improved detection and survival of this highly destructive malignancy. PMID- 22045355 TI - Searching for a system: the quest for ovarian cancer biomarkers. AB - The stark difference in clinical outcome for patients with ovarian cancer diagnosed at early stages (95% survival at 5 years) versus late stages (27.6% survival at 5 years) has driven a decades-long quest for effective biomarkers that will enable earlier detection of ovarian cancer. Yet despite intense efforts, including the application of modern high throughput technologies including transcriptomics and proteomics, there has been little improvement in performance compared to the gold standard of quantifying serum CA125 immunoreactivity paired with transvaginal ultrasound. This review describes the strategies that have been used for identification of ovarian cancer biomarkers, including the recent introduction of novel bioinformatic approaches. Results obtained using high throughput-based vs. biologically rational approaches for the discovery of diagnostic early detection biomarkers are compared and analyzed for functional enrichment. PMID- 22045357 TI - Tumor vascular biomarkers: new opportunities for cancer diagnostics. AB - Tumor vasculature varies significantly from its normal counterpart and displays unique markers. Recent technological advancements including immunohistochemistry laser-capture microdissection (immuno-LCM), genome-wide high-throughput screening, and proteomics have uncovered a vast array of vascular bed-specific markers that may provide a platform for discovery of new therapeutics directed against various malignancies. However, an essential step in the translation of these markers to clinical application will be the identification of those biomarkers with the highest diagnostic and therapeutic potential. The aim of the current review is to provide a synopsis of recent advancements in the identification of tumor vasculature biomarkers. PMID- 22045358 TI - Glycomic analysis of ovarian cancer: past, present, and future. AB - Glycosylation is undeniably the most complex posttranslational modification. Glycan structures found on proteins and lipids are diverse, often changing in different tissues from normal physiologic conditions to diseases such as cancer. Glycomics encompasses the study of glycans along with the proteins and lipids to which they are attached. In this review we will discuss the glycomics of ovarian cancer from the pre- mass spectrometry era to current discoveries and finally to future potential clinical applications of research based on glycomic discoveries. PMID- 22045359 TI - Tumor-derived exosomes as mediators of disease and potential diagnostic biomarkers. AB - Tumor cells release membranous structures, defined as microvesicles or exosomes, consisting of an array of macromolecules derived from the originating cells, including proteins, lipids, and RNA. The expression of antigenic molecules recognizable by T cells originally suggested a role for these vesicles as a cell free antigen source for anti-cancer vaccines; however, evidence demonstrates that tumor exosomes can exert a broad array of detrimental effects on the immune system - ranging from apoptosis of activated cytotoxic T cells to impairment of monocyte differentiation into dendritic cells, to induction of myeloid suppressive cells. Immunosuppressive exosomes of tumor origin can be found in neoplastic lesions and biologic fluids from cancer patients, implying a potential role of these pathways in in vivo tumor progression and systemic paraneoplastic syndromes. Through the expression of molecules involved in angiogenesis promotion, stromal remodeling, signaling pathway activation through growth factor/receptor transfer, chemoresistance, and intercellular genetic exchange, tumor exosomes could represent a central mediator of the tumor microenvironment. Their release by tumor cells may represent the future for targeting therapeutic interventions and for development of multiplexed diagnostic biomarkers. PMID- 22045360 TI - Discovery and validation of ovarian cancer biomarkers utilizing high density antibody microarrays. AB - Here we demonstrate the utility of high-density antibody microarrays for ovarian cancer biomarker discovery. This report describes the technology and how it can be optimized for hypothesis-generating and testing experiments. Our previous results validated the high density antibody array technology platform, the current work expands on it utilizing a second generation array that we tested with a larger set of ovarian case and control serum samples. We then describe our strategies and methods for result validation, including Western immunoblots to confirm antibody specificity. By comparing and combining the current results with our previous study, we solidified the case that the markers found could be used for ovarian cancer diagnosis using this technology. These results set the stage for further validation of these potential biomarkers and the use of this technology in future biomarker discovery studies. PMID- 22045356 TI - Prognostic biomarkers in ovarian cancer. AB - Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy despite several decades of progress in diagnosis and treatment. Taking advantage of the robust development of discovery and utility of prognostic biomarkers, clinicians and researchers are developing personalized and targeted treatment strategies. This review encompasses recently discovered biomarkers of ovarian cancer, the utility of published prognostic biomarkers for EOC (especially biomarkers related to angiogenesis and key signaling pathways), and their integration into clinical practice. PMID- 22045361 TI - The Journal of Cancer Survivorship: retrospective and future directions. AB - This editorial provides an up-to-date breakdown of the topics accepted for publication in the Journal of Cancer Survivorship: Research and Practice. The paper also indicates priority problem areas that require attention now and in the future. I also want to take this opportunity to announce that the application for the journal to receive an impact rating as of 2012 was approved. This completes two major milestones (indexing by the National Institute of Medicine and calculation of the journal's scientific impact as of 2012). Now it is up to the scientific and health care communities to help further ensure the journal's position as a major resource for information on cancer survivorship. We seek your help in making this a reality. PMID- 22045362 TI - Potential pitfalls of crossover and thoughts on iniparib in triple-negative breast cancer. AB - As recruitment for oncology clinical trials has become more difficult, there appears to have been an increase in the number of studies that allow patients in the control arm to "crossover" and receive the experimental therapy after disease progression. Although some researchers worry that allowing such crossover may abolish gains in progression-free survival in the experimental arm, the possibility that crossover might inadvertently benefit the experimental arm has not been addressed. In clinical trials in which the experimental agent has little or no intrinsic activity and is used to modulate an active combination, such crossover might negatively affect the overall survival of the control arm. Because resistance to the active combination--manifested as disease progression- has occurred, the likelihood of benefit from adding the experimental drug is reduced. Consequently, patients who were randomly assigned to the control arm continue to receive the now inactive combination after crossover, whereas patients in the experimental arm who discontinue study participation may seek out potentially effective salvage regimens. This difference in subsequent therapies may confer an advantage to the experimental arm that is manifested as gains beyond those achieved in progression-free survival, gains that occur not because the experimental therapy induced a change in tumor biology that persists beyond treatment discontinuation but because the control arm suffers by continuing to receive a therapy on which their tumor is progressing. Such an outcome may explain the recently reported trial results for iniparib in triple-negative breast cancer. Given that allowing patients in the control arm to receive the experimental agent may confound interpretation of overall survival, such crossover should not be used indiscriminately, especially if the experimental agent has little or no intrinsic activity. PMID- 22045363 TI - The Orthostatic Hypotension Questionnaire (OHQ): validation of a novel symptom assessment scale. AB - BACKGROUND: There is no widely accepted validated scale to assess the comprehensive symptom burden and severity of neurogenic orthostatic hypotension (NOH). The Orthostatic Hypotension Questionnaire (OHQ) was developed, with two components: the six-item symptoms assessment scale and a four-item daily activity scale to assess the burden of symptoms. Validation analyses were then performed on the two scales and a composite score of the OHQ. METHODS: The validation analyses of the OHQ were performed using data from patients with NOH participating in a phase IV, double blind, randomized, cross over, placebo controlled trial of the alpha agonist midodrine. Convergent validity was assessed by correlating OHQ scores with clinician global impression scores of severity as well as with generic health questionnaire scores. Test-retest reliability was evaluated using intraclass correlation coefficients at baseline and crossover in a subgroup of patients who reported no change in symptoms across visits on a patient global impression scores of change. Responsiveness was examined by determining whether worsening or improvement in the patients' underlying disease status produced an appropriate change in OHQ scores. RESULTS: Baseline data were collected in 137 enrolled patients, follow-up data were collected in 104 patients randomized to treatment arm. Analyses were conducted using all available data. The floor and ceiling effects were minimal. OHQ scores were highly correlated with other patient reported outcome measures, indicating excellent convergent validity. Test-retest reliability was good. OHQ scores could distinguish between patients with severe and patients with less severe symptoms and responded appropriately to midodrine, a pressor agent commonly used to treat NOH. CONCLUSION: These findings provide empirical evidence that the OHQ can accurately evaluate the severity of symptoms and the functional impact of NOH as well as assess the efficacy of treatment. PMID- 22045364 TI - Relation between perceived blood loss and vasovagal symptoms in blood donors. AB - INTRODUCTION/RESULTS: This study examined whether a belief of significant blood loss may be associated with vasovagal symptoms, irrespective of actual blood loss. Individual differences in vasovagal symptoms among blood donors who had an equivalent amount of blood withdrawn were significantly associated with their rating of perceived blood loss. CONCLUSION: The anticipation or belief of blood loss, and perhaps more remotely associated ideas, may trigger processes similar to those induced by actual hemorrhage though further research is required to address other possibilities such as the inflation of ratings by vasovagal symptoms. PMID- 22045365 TI - Heart rate variability analysis of normal and growth restricted children. AB - INTRODUCTION: Intrauterine growth restriction (IUGR) has been associated with an increased risk of cardiovascular disease in later life. The regularity mechanism of cardiovascular system is under the control of autonomic nervous system (ANS). The non-optimal fetal growth may alter the development of the ANS and this appears to persist in later life. The aim of the present work is to analyse the synergic activity of the ANS in normal and growth restricted children. MATERIAL AND METHODS: Heart rate variability analysis from 24 h ECG recordings of 70 children between 9 and 10 years old, normal and IUGR was performed using linear and non-linear time series analysis techniques. CONCLUSION: The HRV parameters showed no significant difference between normal and IUGR children. Low birth weight and its association with development of the cardiovascular system and its control have been extensively studied. In order to investigate the effect of low birth weight on HRV parameters, the IUGR children were further divided into two groups: IUGR-1 (birth weight<2.50 kg) and IUGR-2 (birth weight>=2.50 kg). The results demonstrated that most of the HRV measures showed significant differences between normal versus IUGR-1 as well as IUGR-1 versus IUGR-2 groups. The effect of gender on HRV measures was also examined and we noticed that girls had lower HRV than boys. PMID- 22045366 TI - Foreword: quality improvement efforts: advancing the science of palliative care. PMID- 22045367 TI - Implementation and evaluation of an automated patient death notification policy at a tertiary pediatric oncology referral center. AB - BACKGROUND: Not knowing about a child's death can result in poor quality of care coordination among staff and poor quality bereavement care for families. The purpose of this project was to create, implement, and evaluate an automated Patient Death Notification policy and procedure (PDNPP). MEASURES: Baseline and follow-up surveys of clinical staff. INTERVENTION: Implementation of a PDNPP that created an automated, systematic process for staff notification of patient deaths. OUTCOMES: Ninety-six percent of the staff rated the PDNPP as a significant improvement; 91% reported being "very" or "somewhat" satisfied with the PDNPP, whereas only 44% of the staff were satisfied with the process at baseline. CONCLUSIONS/LESSONS LEARNED: Implementation of an automated PDNPP was feasible and improved staff satisfaction about how they were informed of patient deaths. Staff also reported being notified about patient deaths more quickly, performing their jobs more efficiently, being able to avoid doing something that might upset the deceased patient's family, and being able to better provide support to bereaved families. PMID- 22045368 TI - A rapid two-stage screening protocol for palliative care in the emergency department: a quality improvement initiative. AB - BACKGROUND: A rapid two-stage screening protocol was developed to improve referral for palliative care needs among frail elderly in the emergency department (ED). MEASURES: A new triage tool was administered, with assessment tools for activities of daily living, performance, functional staging, symptom burden, and caregiver distress. INTERVENTION: Stage One identified elderly patients meeting criteria for life-limiting conditions. Stage Two referred patients with crescendo losses in activities of daily living, high symptom burden, and caregiver distress to palliative care or hospice. OUTCOMES: Over eight months, 1587 patients were screened, representing 22% of ED visits made by patients older than 65 years during this time period. Of these, 140 met functional decline criteria, and 51 of these needed palliative care consultation. Five patients were referred to hospice, 20 received palliative care, and 26 received no further service. CONCLUSIONS/LESSONS LEARNED: The project shows unmet needs among elderly ED patients, and the feasibility of rapid screening and referral using a quality improvement approach. At its peak, the project accounted for half the referrals to the palliative care consultation service. PMID- 22045369 TI - Collecting data on quality is feasible in community-based palliative care. AB - BACKGROUND: Quality measurement in palliative care requires robust data from standardized data collection processes. We developed and tested the feasibility of the Quality Data Collection Tool version 1.0 (QDACTv1.0) for use in community based palliative care. MEASURES: To evaluate for implementation barriers, we tested feasibility, acceptability, and utility of the QDACTv1.0 by reviewing use patterns, surveying clinician users, and reporting conformance with quality metrics. INTERVENTION: Comprising 37 questions within five domains, QDACTv1.0 was launched in May 2008 for data collection at point of care. OUTCOMES: Through March 2011, data on 5959 patients in 19,734 visits have been collected. We observed steady quarterly growth in data collection, positive clinician feedback, and successful mapping of data to quality metrics. Information gathered characterized practice variations and suggested quality improvement initiatives. Clinician feedback has driven updating to Quality Data Collection Tool version 2.0. CONCLUSIONS/LESSONS LEARNED: Standardized data collection is feasible in routine community-based palliative care and is valuable for quality monitoring. PMID- 22045370 TI - Implementation and evaluation of a network-based pilot program to improve palliative care in the intensive care unit. AB - BACKGROUND: Intensive care unit (ICU) care could be improved by implementation of time-triggered evidence-based interventions including identification of a patient/family medical decision maker, the patient's advance directive status, and cardiopulmonary resuscitation preferences by Day 1; offer of social work and spiritual support by Day 3; and a family meeting establishing goals of care by Day 5. We implemented a program to improve care for ICU patients in five Department of Veterans Affairs' ICUs. MEASURES: We measured the percent of ICU patients with lengths of stay of five or more days that received the care processes by the appropriate day. INTERVENTION: Critical care and palliative care providers trained ICU nurse teams to improve care through auditing, performance feedback, improvement tools, education, and monthly team meetings. OUTCOMES: Pre- and postintervention care were compared. Offering social work and spiritual support, identification of the medical decision maker, and documentation of family meetings significantly improved. CONCLUSIONS/LESSONS LEARNED: ICU nurse teams can be engaged to improve care under the aegis of a collaborative quality improvement project. PMID- 22045371 TI - Using the improving palliative care in the intensive care unit (IPAL-ICU) project to promote palliative care consultation. AB - BACKGROUND: The Improving Palliative Care in the Intensive Care Unit (IPAL-ICU) project is an initiative designed to improve the quality of palliative care in the intensive care unit. One of the problems to be addressed is the underutilization of palliative care. MEASURES: The percentage change in number of palliative care consults in the Medical ICU (MICU) and Surgical ICU (SICU) compared with the same time period the previous year was used as an objective measure to indicate increased utilization of palliative care. INTERVENTION: Two hundred seventy-three patients were screened for potential palliative care consultation. After each patient screening, the attending physician was offered the opportunity to consult the palliative care consultation team. OUTCOMES: In comparison with the same time period the previous year, an increase in palliative care consults of 113% in the MICU and of 51% in the SICU was noted during the screening period. CONCLUSIONS/LESSONS LEARNED: The IPAL-ICU project framework and recommendations can be effectively used to increase the number of palliative care consults in the ICU. PMID- 22045372 TI - A model for increasing palliative care in the intensive care unit: enhancing interprofessional consultation rates and communication. AB - BACKGROUND: Only a minority of patients who die in the medical intensive care unit (MICU) receive palliative care services. At the South Texas Veterans Health Care System Audie L. Murphy Hospital, only 5% of patients who died in the MICU from May to August 2010 received a palliative care consultation. MEASURES: We measured the percentage of MICU patients for which there was a palliative care consultation during the intervention period. INTERVENTION: Starting October 1, 2010 and ending April 30, 2011, the palliative care and MICU teams participated in daily "pre-rounds" to identify patients at risk for poor outcomes, who may benefit from a palliative care consultation. OUTCOMES: Palliative care consultation increased significantly from 5% to 59% for patients who died in the MICU during the intervention period. Additionally, palliative care consultation increased from 5% to 21% for all patients admitted to the MICU during the intervention period. CONCLUSIONS/LESSONS LEARNED: Daily pre-rounds between the palliative care and MICU teams increased palliative care services for MICU patients at risk for poor outcomes, who may benefit from a palliative care consultation. PMID- 22045373 TI - Characterization of abdominal pain during methylnaltrexone treatment of opioid induced constipation in advanced illness: a post hoc analysis of two clinical trials. AB - CONTEXT: Methylnaltrexone is a selective peripherally acting mu-opioid receptor antagonist that decreases the constipating effects of opioids without affecting centrally mediated analgesia. In two double-blind, placebo-controlled, Phase III studies of methylnaltrexone for opioid-induced constipation in patients with advanced illness, abdominal pain was the most common adverse event (AE) reported. OBJECTIVES: This analysis sought to further characterize the Medical Dictionary for Regulatory Activities-defined abdominal pain AEs experienced in these studies. METHODS: A post hoc analysis of verbatim descriptions was used to further assess AEs characterized as abdominal pain in both trials. Descriptive summary statistics were used to assess severity of abdominal pain, effect of abdominal pain on global pain scores, and other characteristics. Logistic regression analysis was used to determine the association of baseline characteristics with abdominal pain. RESULTS: Most verbatim descriptions of abdominal pain referred to "abdominal cramps" or "cramping." Abdominal pain AEs were mostly mild to moderate in severity and did not affect patients' global evaluation of pain. The incidence of abdominal pain AEs in methylnaltrexone treated patients was greatest after the first dose and decreased with subsequent doses. No association between abdominal pain AEs and most baseline patient characteristics was noted. CONCLUSION: Abdominal pain AEs in methylnaltrexone treated patients in clinical trials are usually described as "cramps" or "cramping," are mostly mild to moderate in severity, and decrease in incidence with subsequent dosing. PMID- 22045374 TI - Responding to surrogate requests that seem inconsistent with a patient's living will. AB - Clinicians may feel conflicted when a patient's legal decision maker is making decisions that seem inconsistent with a patient's living will. We provide evidence-based information to help clinicians consider whether a surrogate's inconsistent decisions are ethically appropriate. Surrogates are not flawless translators of their loved one's preferences; they are influenced by their own hopes and the current clinical context. Patients may be aware of this, are often concerned about burdening their loved ones, and often grant their surrogates leeway in interpreting their wishes. When appropriate, clinicians should respect surrogates' interpretations of patient values and take steps to decrease surrogate stress during the decision-making process. Finally, if clinicians are cognizant of their own values and preferences, they may recognize how these may affect their responses to certain clinical cases. PMID- 22045375 TI - Rembrandt, michelangelo, and stories of healing. AB - Two contemporary patient narratives provide an opportunity to reflect on the role of clinicians in the healing process, as seen in the works of Rembrandt and Michelangelo. PMID- 22045376 TI - Anti-epileptic drugs. AB - Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. Additional content is available on www.palliativedrugs.com. Country-specific books (Hospice and Palliative Care Formulary USA, and Palliative Care Formulary, British and Canadian editions) are also available and can be ordered from www.palliativedrugs.com. The series editors welcome feedback on the articles (hq@palliativedrugs.com). PMID- 22045378 TI - From adaptation to molecular evolution. PMID- 22045379 TI - Dangers of 'adaptation'. PMID- 22045380 TI - Evolution of adaptive phenotypic traits without positive Darwinian selection. AB - Recent evidence suggests the frequent occurrence of a simple non-Darwinian (but non-Lamarckian) model for the evolution of adaptive phenotypic traits, here entitled the plasticity-relaxation-mutation (PRM) mechanism. This mechanism involves ancestral phenotypic plasticity followed by specialization in one alternative environment and thus the permanent expression of one alternative phenotype. Once this specialization occurs, purifying selection on the molecular basis of other phenotypes is relaxed. Finally, mutations that permanently eliminate the pathways leading to alternative phenotypes can be fixed by genetic drift. Although the generality of the PRM mechanism is at present unknown, I discuss evidence for its widespread occurrence, including the prevalence of exaptations in evolution, evidence that phenotypic plasticity has preceded adaptation in a number of taxa and evidence that adaptive traits have resulted from loss of alternative developmental pathways. The PRM mechanism can easily explain cases of explosive adaptive radiation, as well as recently reported cases of apparent adaptive evolution over ecological time. PMID- 22045381 TI - Centromere repositioning in mammals. AB - The evolutionary history of chromosomes can be tracked by the comparative hybridization of large panels of bacterial artificial chromosome clones. This approach has disclosed an unprecedented phenomenon: 'centromere repositioning', that is, the movement of the centromere along the chromosome without marker order variation. The occurrence of evolutionary new centromeres (ENCs) is relatively frequent. In macaque, for instance, 9 out of 20 autosomal centromeres are evolutionarily new; in donkey at least 5 such neocentromeres originated after divergence from the zebra, in less than 1 million years. Recently, orangutan chromosome 9, considered to be heterozygous for a complex rearrangement, was discovered to be an ENC. In humans, in addition to neocentromeres that arise in acentric fragments and result in clinical phenotypes, 8 centromere-repositioning events have been reported. These 'real-time' repositioned centromere-seeding events provide clues to ENC birth and progression. In the present paper, we provide a review of the centromere repositioning. We add new data on the population genetics of the ENC of the orangutan, and describe for the first time an ENC on the X chromosome of squirrel monkeys. Next-generation sequencing technologies have started an unprecedented, flourishing period of rapid whole genome sequencing. In this context, it is worth noting that these technologies, uncoupled from cytogenetics, would miss all the biological data on evolutionary centromere repositioning. Therefore, we can anticipate that classical and molecular cytogenetics will continue to have a crucial role in the identification of centromere movements. Indeed, all ENCs and human neocentromeres were found following classical and molecular cytogenetic investigations. PMID- 22045382 TI - Intrachromosomal rearrangements in avian genome evolution: evidence for regions prone to breakpoints. AB - It is generally believed that the organization of avian genomes remains highly conserved in evolution as chromosome number is constant and comparative chromosome painting demonstrated there to be very few interchromosomal rearrangements. The recent sequencing of the zebra finch (Taeniopygia guttata) genome allowed an assessment of the number of intrachromosomal rearrangements between it and the chicken (Gallus gallus) genome, revealing a surprisingly high number of intrachromosomal rearrangements. With the publication of the turkey (Meleagris gallopavo) genome it has become possible to describe intrachromosomal rearrangements between these three important avian species, gain insight into the direction of evolutionary change and assess whether breakpoint regions are reused in birds. To this end, we aligned entire chromosomes between chicken, turkey and zebra finch, identifying syntenic blocks of at least 250 kb. Potential optimal pathways of rearrangements between each of the three genomes were determined, as was a potential Galliform ancestral organization. From this, our data suggest that around one-third of chromosomal breakpoint regions may recur during avian evolution, with 10% of breakpoints apparently recurring in different lineages. This agrees with our previous hypothesis that mechanisms of genome evolution are driven by hotspots of non-allelic homologous recombination. PMID- 22045383 TI - A concise route to the macrocyclic core of the rakicidins. AB - An efficient synthesis of the macrolactone core of the rakicidins is described. The rakicidins are cytotoxic lipopeptides with interesting cancer cell selectivities including HIF-1-independent hypoxia-selective cytotoxicity and anti invasive activity. Access to the core may now allow establishment of preliminary SAR and exploration of routes to several members of rakicidins. PMID- 22045384 TI - The synthesis and role of taurine in the Japanese eel testis. AB - In teleost fish, the progestin 17alpha, 20beta-dihydroxy-4-pregnen-3-one (DHP) is an essential component of the spermatogenesis pathway. In a series of investigations on the mechanisms underlying progestin-stimulated spermatogenesis, we have found that DHP up-regulates the expression of cysteine dioxygenase1 (CDO1) in the Japanese eel testis. CDO1 is one of the enzymes involved in the taurine biosynthesis pathway. To evaluate whether taurine is synthesized in the eel testis, cysteine sulfinate decarboxylase (CSD), another enzyme involved in taurine synthesis, was isolated from this species. RT-PCR and in vitro eel testicular culture revealed that although CSD was also expressed in eel testis, neither DHP nor other sex steroids affect CSD mRNA expression in a similar manner to CDO1. Using an in vitro eel testicular culture system, we further investigated the effects of DHP on taurine synthesis in the eel testis. HPLC analysis showed that DHP treatment significantly increases the taurine levels in the eel testis. These results suggest that DHP promotes taurine synthesis via the up-regulation of CDO1 mRNA expression during eel spermatogenesis. Furthermore, we observed from our analysis that although taurine does not induce complete spermatogenesis, it promotes spermatogonial DNA synthesis and the expression of Spo11, a meiosis specific marker. These data thus suggest that taurine augments the effects of sex steroids in the promotion of spermatogonial proliferation and/or meiosis and hence that taurine plays important roles in spermatogenesis. PMID- 22045385 TI - Intraperitoneal injection of saline modulates hippocampal brain receptor complex levels but does not impair performance in the Morris Water Maze. AB - The involvement of the hippocampus in pain has been demonstrated but key players, i.e. the major brain receptors have not been shown to be modulated by pain. It was therefore the aim of the study to show the concerted action and pattern of brain receptor complex levels in a non-invasive model of moderate pain. C57BL/6J mice were divided into four groups of 14 animals each: trained injected, trained non-injected, yoked injected and yoked non-injected. Animals were tested in the open field and the elevated plus maze for behavioural evaluation and cognitive functions were tested using the Morris Water Maze. Hippocampi were taken 6 h following sacrification. Membrane proteins were prepared by ultracentrifugation and run on blue native gels to keep the native state, blotted to membranes and western blotting was carried out using the primary antibodies against serotonin receptor 5HT1A, muscarinic acetylcholine receptor M1 (mAChR-M1), nicotinic acetylcholine receptor alpha7 (nAChR-alpha7), glutamate (AMPA) receptor (GluR1) and neurokinin receptor 1 (NK-1). There was no difference between performance in behaviour or in the MWM between groups. Brain receptor level changes involved all receptors given above. Pain affected mAChR-M1, GluR1 and NK-1 complex levels when yoked-injected were compared with yoked non-injected animals. Memory mechanisms affected mAChR-M1 complex levels when trained non-injected animals were compared with yoked non-injected controls. Taken together, the neurochemical basis for testing receptor agonists/antagonists on the role of pain and the hippocampus was generated that may be useful for interpretations of the role of this complex area in moderate pain. PMID- 22045386 TI - Transglutaminase 2 and Factor XIII catalyze distinct substrates in differentiating osteoblastic cell line: utility of highly reactive substrate peptides. AB - Differentiated osteoblastic cell line, MC3T3-E1 expresses transglutaminase 2 (TG2) and Factor XIII (FXIII). In previous studies, we identified isozyme specific and highly reactive glutamine-donor substrate peptides (pepF11KA and pepT26) for each isozyme. Using these peptides, we compared the reaction products with lysine-donor substrates for each isozyme in differentiating MC3T3-E1 cells. By this analysis, distinct substrates for the activated TG2 and FXIII were detected in cultured cellular extract. Possible substrates that incorporated biotin-labeled peptides were further purified using streptavidin-affinity chromatography. Several isozyme-specific substrates were identified by mass spectrometry analysis of the purified fractions. These analyses also indicate the benefit of the substrate peptides for obtaining distinct substrates in a reaction mixture where two isozymes co-exist. PMID- 22045387 TI - High effectiveness of pandemic influenza A (H1N1) vaccination in healthcare workers from a Portuguese hospital. AB - OBJECTIVES: Vaccination of healthcare workers (HCWs) was made a high priority during the phase six pandemic of the novel influenza A H1N1 (pH1N1) virus. We surveyed adherence to pH1N1 vaccination and the incidence of pH1N1 infection between vaccinated and unvaccinated HCWs. METHODS: Employees at the S. Joao Hospital in Porto, Portugal, were offered pH1N1 vaccinations free of charge. Pandemrix((r)) was the vaccine administered. As part of the pandemic plan, employees with influenza-like symptoms (ILS) were called upon to take an RT-PCR H1N1 test. If the test results were positive, they had to stay off work for at least 7 days. Sociodemographic data, vaccination status, contact with infectious patients, ILS and pH1N1 test results were documented in a standardised manner. RESULTS: The survey population comprised 5,592 employees. The vaccination rate was 30.8% (n = 1,720) for pH1N1 and 50.4% (n = 2,819) for the 2009/2010 seasonal trivalent inactivated influenza vaccine (TIV). One mild anaphylactic reaction occurred after pH1N1 vaccination. Minor local side effects occurred more often after pH1N1 vaccination than after 2009/2010 seasonal TIV (38.0% vs. 12.3%). Pandemic H1N1 infection was diagnosed in 97 HCWs (1.7%). Compared to employees with no regular patient contact, nurses (2.8%) had the highest risk of pH1N1 infection (adjusted OR 3.8; 95% CI 1.2-6.8). Vaccination reduced the pH1N1 infection risk (OR 0.12; 95% CI 0.05-0.29). Vaccine effectiveness was 90.4% (95% CI 73.5-97.3%). CONCLUSION: Vaccination reduced the pH1N1 infection risk considerably. The pandemic plan to contain the pH1N1 infection was successful. Nurses had the highest risk of pH1N1 infection and are therefore a target group for vaccination measures. PMID- 22045388 TI - A multicenter study to map genes for Fuchs endothelial corneal dystrophy: baseline characteristics and heritability. AB - PURPOSE: To describe the methods for family and case-control recruitment for a multicenter genetic and associated heritability analyses of Fuchs endothelial corneal dystrophy (FECD). METHODS: Twenty-nine enrolling sites with 62 trained investigators and coordinators gathered individual and family information, graded the phenotype, and collected blood and/or saliva for genetic analysis on all individuals with and without FECD. The degree of FECD was assessed in a 0 to 6 semiquantitative scale using standardized clinical methods with pathological verification of FECD on at least 1 member of each family. Central corneal thickness was measured by ultrasonic pachymetry. RESULTS: Three hundred twenty two families with 330 affected sibling pairs with FECD were enrolled and included a total of 650 sibling pairs of all disease grades. Using the entire 7-step FECD grading scale or a dichotomous definition of severe disease, heritability was assessed in families via sib-sib correlations. Both binary indicators of severe disease and semiquantitative measures of disease severity were significantly heritable, with heritability estimates of 30% for severe disease, 37% to 39% for FECD score, and 47% for central corneal thickness. CONCLUSIONS: Genetic risk factors have a strong role in the severity of the FECD phenotype and corneal thickness. Genotyping this cohort with high-density genetic markers followed by appropriate statistical analyses should lead to novel loci for disease susceptibility. PMID- 22045389 TI - Tomographic corneal profile analysis of central toxic keratopathy after LASIK. AB - PURPOSE: To describe a case of bilateral central toxic keratopathy (CTK) in a post-laser in situ keratomileusis-treated patient using tomographic methods for more than a 1-year follow-up. METHODS: Case report and literature review. RESULTS: Tomographic analysis of a patient with bilateral CTK revealed flattening of the anterior cornea curvature and thinning at the level of anterior stromal bed, with minimal changes of the posterior curvature. A thin central flap was also noted on optical coherence tomography (OCT). Over the course of a year, the patient's hyperopic shift resolved with steepening of the anterior curvature and concomitant thickening of the flap and stromal bed. CONCLUSIONS: Using Scheimpflug imaging and Visante OCT, we demonstrated that the hyperopia that accompanies CTK is related to anterior corneal curvature changes. We also found that the majority of corneal tissue loss occurs at the anterior stromal bed mainly in the first postoperative week and is followed by a regeneration of tissue. A thin central flap was noted, and it is not clear whether this was created intraoperatively or resulted from the presence of CTK, requiring further study. PMID- 22045390 TI - Fungal keratitis caused by Chaetomium atrobrunneum. AB - PURPOSE: We report a case of mycotic keratitis caused by a rare fungus Chaetomium atrobrunneum. METHODS: Clinical examination, slit-lamp examination, and microbiological evaluation of corneal ulcer were done, and its treatment outcome was studied. The fungal etiology was established by conventional microbiological techniques: polymerase chain reaction and speciation by DNA sequencing. RESULTS: Based on morphological features of the isolate and DNA sequence analysis of the internal transcribed spacer region, the isolate was identified as C. atrobrunneum. The keratitis was resolved completely by topical natamycin and oral ketoconazole. CONCLUSION: To best of our knowledge, this is the first reported case of keratitis caused by a rare fungus, C. atrobrunneum, which was successfully treated with dual therapy. PMID- 22045391 TI - Endothelial keratoplasty in a newborn baby with CHED. AB - PURPOSE: Congenital hereditary endothelial dystrophy (CHED) may be present at birth in the form of whitish cloudy corneas. Descemet stripping endothelial keratoplasty has been attempted to solve the problem but never in babies. We report a case of successful bilateral surgery in a 3-month-old baby. METHODS: CHED was detected at birth in a newborn female, but surgery was deferred to increase the chance of success. At 3 months, endothelial keratoplasty was performed in the left eye without any attempt to remove the existing endothelium. As the cornea cleared up soon after the surgery, the right eye was operated 4 weeks later. RESULTS: Both corneas were clear 10 and 9 months after the surgery, respectively. Central thickness was 580 MUm in the right eye and 530 MUm in the left eye. The baby followed the light and started smiling at the lactating mother. There were no signs of graft rejection. Steroid eye drops are currently employed. CONCLUSIONS: Endothelial keratoplasty without endothelium removal has been successfully employed in a newborn with CHED for the first time. This procedure may be the best option for newborns with cloudy corneas. PMID- 22045393 TI - Utilization of radionuclide myocardial perfusion imaging in two health care systems: assessment with the 2009 ACCF/ASNC/AHA appropriateness use criteria. AB - BACKGROUND: Although differences in the rate of utilization of invasive cardiac procedures between Veterans Affairs (VA) hospitals and other health care systems are present, noninvasive cardiac imaging use pattern has not been well studied. We evaluated the ability of the updated appropriateness use criteria (AUC) to determine utilization patterns of myocardial perfusion imaging (MPI) and compare use between an academic practice and a VA. METHODS: One-hundred fifty stress/rest MPI studies in an academic practice and 150 at a VA hospital were retrospectively reviewed using the hierarchical approach published in the 2009 AUC. RESULTS: Less than 1% of studies were unclassified. A higher percentage of MPI were requested for inappropriate reason at the VA, although this difference was not statistically significant (P = .248). In the VA, non-physicians requested significantly more inappropriate studies than physicians (26.8% vs 20.1%; P < .048). Within the academic practice non-cardiologists referred more patients for inappropriate indications than cardiologists (23.9% vs 10.1%; P = .001). Five most common inappropriate indications accounted for the vast majority of inappropriately requested MPI (77%). CONCLUSIONS: The revised 2009 AUC allow for near complete categorization of appropriateness in testing. Differences between institutions and provider types were noted and areas for improved utilization were identified. PMID- 22045394 TI - Nomograms for estimating coronary artery disease prognosis with gated stress myocardial perfusion SPECT. AB - BACKGROUND: Nomograms can be useful tools for estimating coronary artery disease (CAD) risk. We sought to devise risk-based nomograms for stress myocardial perfusion SPECT to include measures of % ischemic myocardium and left ventricular function. METHODS: A total of 4,575 patients were consecutively and prospectively enrolled in the Myoview Prognosis Registry. Multivariable Cox proportional hazards model were employed to estimate CAD death or MI. Nomograms were devised from the results of the Cox models. RESULTS: CAD death or MI rates worsened in a gradient manner by the % ischemic myocardium. Higher risk patients were those with a rest and/or post-stress LVEF <= 45%. A nomogram was developed to estimate 2-year CAD death or MI-free survival for exercising and pharmacologic stress patients by their post-stress LVEF and % ischemic myocardium MPS results. Patients undergoing pharmacologic stress with a rest and/or post-stress LVEF <= 45% with high risk ischemic findings had the lowest CAD death or MI event-free survival. For exercising patients with a preserved resting LVEF > 45%, 2-year CAD death or MI event-free survival ranged from 99.4% to 89% for 0% to >=20% ischemic myocardium. Those at highest risk included patients undergoing pharmacologic stress with depressed LVEF. For pharmacologic stress patients with a resting LVEF <=45%, 2-year CAD death or MI event-free survival ranged from 89% to 48% for 0% to >=20% ischemic myocardium. For pharmacologic stress patients with a post stress LVEF <= 45%, 2-year CAD death or MI event-free survival ranged from 88% to 46% for 0% to >=20% ischemic myocardium. A validation cohort revealed moderate strong correlation between observed and predicted survival (r = 0.71). Average discordance between observed and predicted survival was <=2% but was greater for higher risk patients with lower predicted survival estimates. CONCLUSIONS: Risk based nomograms estimating important CAD outcomes may serve as a clinically useful tool to target therapeutic intervention for high risk patient subsets. PMID- 22045396 TI - Diagnostic and prognostic markers in liver cirrhosis. PMID- 22045397 TI - Classification of cirrhosis: the clinical use of HVPG measurements. AB - The modern paradigm considers cirrhosis as a dynamic and potentially reversible disease. It consists of two different entities, compensated and decompensated cirrhosis, each with a distinct prognosis and different predictors of survival. The development of portal hypertension is a hallmark in the history of cirrhosis, and its progression parallels that of the disease. In consequence, portal pressure measurement by means of HVPG allows stratifying cirrhosis in stages with defined outcomes, prognosis, and management strategies. PMID- 22045398 TI - Non-invasive diagnostic and prognostic evaluation of liver cirrhosis and portal hypertension. AB - Cirrhosis is the final stage of most of chronic liver diseases, and is almost invariably complicated by portal hypertension, which is the most important cause of morbidity and mortality in these patients. This review will focus on the non invasive methods currently used in clinical practice for diagnosing liver cirrhosis and portal hypertension. The first-line techniques include physical examination, laboratory parameters, transient elastography and Doppler-US. More sophisticated imaging methods which are less commonly employed are CT scan and MRI, and new technologies which are currently under evaluation are MR elastography and acoustic radiation force imaging (ARFI). Even if none of them can replace the invasive measurement of hepatic venous pressure gradient and the endoscopic screening of gastroesophageal varices, they notably facilitate the clinical management of patients with cirrhosis and portal hypertension, and provide valuable prognostic information. PMID- 22045399 TI - Prognostic markers in patients with ascites and hepatorenal syndrome. PMID- 22045400 TI - Prognostic markers in patients with cirrhosis and portal hypertension who have not bled. AB - Prognostic markers of compensated cirrhosis should mainly investigate factors involved with progression to decompensation because death in cirrhosis is related with decompensation. Portal hypertension plays a crucial role in the pathophysiology of most complications of cirrhosis. Accordingly, HVPG monitoring has strong prognostic value. An HVPG >= 10 mmHg determines a significantly higher risk of developing decompensation. Esophageal varices also can develop when the HVPG is >= 10 mmHg, although an HVPG >= 12 mmHg is required for variceal bleeding to occur. Monitoring the changes induced by the treatment of portal hypertension on HVPG, provides strong prognostic information. In compensated cirrhosis hemodynamic response is appropriate when the HVPG decreased to < 10 mmHg or by > 10% from baseline, because the incidence of complications such as bleeding or ascites significantly decrease when these targets are achieved. Whether serum markers, such as the FibroTest, they, may be valuable to predict decompensation should be established. Transient Elastography is a promising technique that has shown an excellent accuracy to detect severe portal hypertension. However, whether it can adequately determine clinically significant portal hypertension, and risk of developing varices and decompensation, should be established. Magnetic Resonance Elastography is also promising. PMID- 22045401 TI - Prognostic evaluation of patients with acute variceal bleeding. PMID- 22045402 TI - Prognostic markers in patients who have recovered from an acute variceal bleeding: role of HVPG measurement. PMID- 22045403 TI - Prognostic assessment in patients with hepatic encephalopathy. AB - Hepatic encephalopathy (HE) is a common complication of liver failure that is associated with poor prognosis. However, the prognosis is not uniform and depends on the underlying liver disease. Acute liver failure is an uncommon cause of HE that carries bad prognosis but is potentially reversible. There are several prognostic systems that have been specifically developed for selecting patients for liver transplantation. In patients with cirrhosis the prognosis of the episode of HE is usually dictated by the underlying precipitating factor. Acute on-chronic liver failure is the most severe form of decompensation of cirrhosis, the prognosis depends on the number of associated organ failures. Patients with cirrhosis that have experienced an episode of HE should be considered candidates for liver transplant. The selection depends on the underlying liver function assessed by the Model for End-stage Liver Disease (MELD) index. There is a subgroup that exhibits low MELD and recurrent HE, usually due to the coexistence of large portosystemic shunts. The recurrence of HE is more common in patients that develop progressive deterioration of liver function and hyponatremia. The bouts of HE may cause sequels that have been shown to persist after liver transplant. PMID- 22045404 TI - Diagnostic and prognostic molecular markers in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, representing also the main cause of death among cirrhotic patients. In contrast to most other solid tumors, the underlying cirrhotic liver disease in HCC patients greatly impairs tumor related prognosis, conferring this neoplasm a unique situation, in which accurate prognostic prediction is a relevant and unmet need. Although clinical staging systems have improved significantly and now comprise tumor characteristics, liver function and patient performance status, the integration of molecular data into these algorithms is still hypothetical. Molecular profiling of HCC has led to a better understanding of the physiopathology of this neoplasm and has allowed developing novel therapeutic approaches (e.g. molecular targeted therapies) for a tumor previously considered as therapy-refractory. Integrative analysis of different reported genomic datasets has revealed common subclasses between different studies, highlighting their biological relevance in HCC. Gene signatures derived from tumors and from the adjacent tissue have been able to differentiate subclasses with different outcomes and have been proposed as potential predictive markers in the clinical setting. Genomic characterization of surrounding non-tumor tissue might be of particular interest to identify patients at high risk of developing HCC and therefore to select those patients that would benefit of potential chemopreventive strategies. Epigenetic analyses (methylation and miRNA profiling) are adding up to the knowlegde derived from gene expression data and should not be forgotten in the molecular diagnosis of HCC. Integrative analyses of genetic and epigenetic information of the tumor and the surrounding tissue should be used to identify novel biomarkers and therapeutic targets in HCC, to improve existing treatment algorithms and to eventually design a more personalized medicine in this devastating disease. PMID- 22045405 TI - Doping of a dielectric layer as a new alternative for increasing sensitivity of the contactless conductivity detection in microchips. AB - This communication describes a new procedure to increase the sensitivity of C(4)D in PDMS/glass microchips. The method consists in doping the insulating layer (PDMS) over the electrodes with nanoparticles of TiO(2), increasing thus its dielectric constant. The experimental protocol is simple, inexpensive, and fast. PMID- 22045406 TI - Influence of substituent and solvent on the radiative process of singlet excited states of novel cyclic azacyanine derivatives. AB - The photophysical properties of novel cyclic azacyanine derivatives have been investigated in acetonitrile, N-butyronitrile, methanol, ethanol, DMF and water. Introduction of electron donating or accepting groups on the cyclic azacyanine has a direct impact on the spectroscopic and photophysical properties. Irrespective of the nature of the substitution, azacyanine shows a general solvent relaxation in accordance with Lippert-Mataga's prediction; however, in protic solvent, specific interactions are encountered. Fluorescence lifetime decay suggests a relaxation in the nanosecond time scale with monoexponential decay in polar solvents and biexponential decay in non polar solvents. The fluorescence lifetime of azacyanines are found to be longer than popular cy3 dyes. An electron donating substituent increases the fluorescence lifetime and influences the radiative process, whereas an electron withdrawing group marginally increases the excited state lifetime but remarkably enhances the radiative process. The fluorescence quantum yield of substituted cyclic azacyanine in water is noted to be at least five fold higher than the popular cy3 dye. PMID- 22045407 TI - Determination of paracetamol based on its quenching effect on the photoluminescence of CdTe fluorescence probes. AB - L-Cysteine capped CdTe nanoparticles (NPs) were synthesized in aqueous medium, and their application as fluorescence probes in the determination of paracetamol was studied. The L-cysteine capped CdTe NPs were characterized by transmission electron microscopy, X-ray diffraction spectrometry, spectrofluorometry, ultraviolet-visible and Fourier transform infrared spectrometry. Based on the distinct fluorescence quenching of CdTe fluorescence probes in the presence of paracetamol, a simple, rapid and specific method for paracetamol determination was presented. Under optimum conditions, the relative fluorescence intensity of CdTe NPs was linearly proportional to paracetamol concentration from 1.0 * 10(-8) mol/L to 1.6 * 10(-7) mol/L with a detection limit of 4.2 * 10(-9) mol/L. The proposed method was applied to detect paracetamol in commercial tablets with satisfactory results. PMID- 22045408 TI - Fe-N-modified multi-walled carbon nanotubes for oxygen reduction reaction in acid. AB - We report a facile synthesis of Fe-N-C catalysts based on the surface functionalization of multi-walled carbon nanotubes (MWCNTs), which show high activity and stability for oxygen reduction reaction (ORR) in acid. Fe-N-MWCNT catalysts, whose ORR mass activities could vary by 3-4 times depending on the choice of Fe precursors, were found to have considerably higher ORR mass activity and higher stability than N-modified MWCNTs (N-MWCNTs). The Fe-N-MWCNT catalyst with a dominant Fe-N(x) moiety (with x ~ 4) and a surface Fe/C ratio of ~0.004 exhibits the highest ORR mass activity in acid (~0.7 mA mg(-1)(Fe-N-MWCNT) at 0.8 V vs. RHE), where the lower mass activity of other Fe-N-MWCNT catalysts can be attributed to lower Fe/C ratios and Fe-N(x) moieties (with x smaller than 4) as revealed from X-ray photoelectron spectroscopy (XPS) and extended X-ray absorption fine structure (EXAFS) spectroscopy. Moreover, the enhanced stability of Fe-N-MWCNTs in comparison to N-MWCNTs can be attributed to less H(2)O(2) production during ORR as determined from rotating ring disk electrode (RRDE) measurements, and higher activity for H(2)O(2) electro-reduction by rotating disk electrode (RDE) measurements. The large surface Fe/C ratio and Fe-N(x) moiety corresponding to high ORR activity and stability of Fe-N-MWCNTs demonstrate that surface functionalization can be very helpful to graft active catalytic sites onto carbon nanostructures, and to provide insights into the ORR mechanism of non noble metal catalysts (NNMCs) for proton exchange membrane fuel cells (PEMFCs). PMID- 22045410 TI - Colored noise in the fluctuations of an extended DNA molecule detected by optical trapping. AB - We studied fluctuations of an optically trapped bead connected to a single DNA molecule anchored between the bead and a cover glass or between two optically trapped beads. Power spectral densities of the bead position for different extensions of the molecule were compared with the power spectral density of the position fluctuations of the same bead without the molecule attached. Experiments showed that the fluctuations of the DNA molecule extended up to 80% by a force of 3 pN include the colored noise contribution with spectral dependence 1/f (alpha) with alpha ~ 0.75. PMID- 22045411 TI - Cardiologists find evidence why too much exercise might be bad for you. PMID- 22045412 TI - Sudden cardiac death in marathon runners: can it be prevented? PMID- 22045413 TI - The physiological effects of low-intensity neuromuscular electrical stimulation (NMES) on short-term recovery from supra-maximal exercise bouts in male triathletes. AB - This study investigated the acute effects of NMES on blood lactate (BLa) and performance parameters in trained male triathletes. On three separate days, 13 trained male triathletes performed six 30 s Wingate tests (30 WanT) on a cycle ergometer. Each session consisted of performing 3 * 30 WanT (bouts 1-3) followed by a randomly assigned 30 min recovery intervention of either: (i) passive (seated), (ii) active (cycling at 30% VO(2 max)) or (iii) NMES (1 Hz/500 MUs ON:OFF 2:6 s). The 3 * 30 WanT bouts were then repeated (bouts 4-6) and compared to bouts 1-3 for peak power (PP), mean power (MP) and fatigue index (FI). BLa and heart rate (HR) were recorded at designated time points throughout. Data were analyzed using repeated measures ANOVA with Tukey's honestly significant difference post hoc test. BLa decreased significantly faster during the active recovery intervention (P < 0.001), however, there were no significant differences between interventions for PP (P = 0.217), MP (P = 0.477) and FI (P = 0.234) when the post intervention bouts (4-6) where compared to the pre intervention bouts (1 3). NMES during recovery was not more effective than active or passive recovery for improving subsequent performance. Despite BLa clearing at a significantly faster rate for the active recovery intervention, PP, MP or FI did not improve significantly compared to NMES and passive. In conclusion, NMES does not appear to be more effective than traditional methods for enhancing short-term recovery from supra-maximal exercise bouts in trained male triathletes. PMID- 22045414 TI - Influence of road incline and body position on power-cadence relationship in endurance cycling. AB - In race cycling, the external power-cadence relationship at the performance level, that is sustainable for the given race distance, plays a key role. The two variables of interest from this relationship are the maximal external power output (P (max)) and the corresponding optimal cadence (C (opt)). Experimental studies and field observations of cyclists have revealed that when cycling uphill is compared to cycling on level ground, the freely chosen cadence is lower and a more upright body position seems to be advantageous. To date, no study has addressed whether P (max) or C (opt) is influenced by road incline or body position. Thus, the main aim of this study was to examine the effect of road incline (0 vs. 7%) and racing position (upright posture vs. dropped posture) on P (max) and C (opt). Eighteen experienced cyclists participated in this study. Experiment I tested the hypothesis that road incline influenced P (max) and C (opt) at the second ventilatory threshold ([Formula: see text] and [Formula: see text]). Experiment II tested the hypothesis that the racing position influenced [Formula: see text], but not [Formula: see text]. The results of experiment I showed that [Formula: see text] and [Formula: see text] were significantly lower when cycling uphill compared to cycling on level ground (P < 0.01). Experiment II revealed that [Formula: see text] was significantly greater for the upright posture than for the dropped posture (P < 0.01) and that the racing position did not affect [Formula: see text]. The main conclusions of this study were that when cycling uphill, it is reasonable to choose (1) a lower cadence and (2) a more upright body position. PMID- 22045415 TI - Single and combined influence of ACE and ACTN3 genotypes on muscle phenotypes in octogenarians. AB - We studied the single and combined influence of the ACE I/D and the ACTN3 R577X polymorphisms on muscle phenotypes (thigh muscles' cross-sectional area assessed with magnetic resonance imaging) and strength (maximal handgrip, 30-s chair stand test), functional ability during activities of daily living (Barthel index) and bone mineral density (proximal femur) in Caucasian (Spanish) community-dwelling old people [n = 81, 59 women; mean age 82.8 +/- 4.8 years (range 71-93 years)]. We found no significantly differences in the aforementioned phenotypes across ACE and ACTN3 genotypes (all P > 0.05), except for handgrip in the ACE I/D recessive model (DD 19.5 +/- 6.7 kg, ID 24.0 +/- 9.1 kg, II 22.1 +/- 7.9; P = 0.047), yet statistical significance disappeared after correction for multiple comparisons. Likewise, the analyses of the combined effects between genotypes did not yield any significant difference (all P > 0.05) between the two 'extreme' genotypes [theoretically 'power or muscularity oriented' [(ACTN3 RR + RX & ACE DD) versus 'non-power' (ACTN3 XX & ACE II + ID)]. The aforementioned analyses were adjusted by sex, age and physical activity levels as covariates. Logistic regression analysis revealed no significant association of single or combined effect of ACE and ACTN3 genotypes or genotype combination group (ACE + ACTN3) with sarcopenia (i.e. being in the lowest 25th sex-specific percentile for a combined score of the muscle and functional phenotypes we measured). Though ACE I/D and ACTN3 R577X polymorphisms are candidates to modulate exercise-related phenotypes in adults, our data suggest that they do not exert a major influence in the muscle phenotypes of old people. More studies with larger sample sizes are needed. PMID- 22045416 TI - The effects of a session of resistance training on sleep patterns in the elderly. AB - The purpose of this study was to evaluate the influence of a session of resistance training on the sleep patterns of elderly people. Forty men aged 65-80 years who were sedentary and clinically healthy were divided into two groups: the control group (n = 18) and the resistance group (n = 22). Both groups underwent two polysomnography tests, one at baseline and another after either a resistance training session (the resistance group) or no physical exercise (the control group). The resistance training session was based on 60% of one repetition maximum (a test that assesses the maximum force). We observed that the frequency with which the control group awoke (arousal index) increased from 16.29 +/- 6.06 events/h to 20.09 +/- 6.9 events/h, and in the resistance group, it decreased from 22.27 +/- 11 events/h to 20.41 +/- 8.57 events/h (t = 2.10 and p = 0.04). For stage-1 sleep, there was an increase from 4.96% at baseline to 5.40% in the control group, and there was a decrease in the resistance group from 8.32 to 6.21% after the exercise session (t = 2.12 and p = 0.04). A session of resistance training at 60% of one repetition maximum was able to modify the sleep pattern in men aged 65-80 years, suggesting that physical exercise has a modest influence on sleep consolidation. PMID- 22045417 TI - Multifaceted SlyD from Helicobacter pylori: implication in [NiFe] hydrogenase maturation. AB - SlyD belongs to the FK506-binding protein (FKBP) family with both peptidylprolyl isomerase (PPIase) and chaperone activities, and is considered to be a ubiquitous cytosolic protein-folding facilitator in bacteria. It possesses a histidine- and cysteine-rich C-terminus binding to selected divalent metal ions (e.g., Ni(2+), Zn(2+)), which is important for its involvement in the maturation processes of metalloenzymes. We have determined the solution structure of C-terminus-truncated SlyD from Helicobacter pylori (HpSlyDDeltaC). HpSlyDDeltaC folds into two well separated, orientation-independent domains: the PPIase-active FKBP domain and the chaperone-active insert-in-flap (IF) domain. The FKBP domain consists of a four stranded antiparallel beta-sheet with an alpha-helix on one side, whereas the IF domain folds into a four-stranded antiparallel beta-sheet accompanied by a short alpha-helix. Intact H. pylori SlyD binds both Ni(2+) and Zn(2+), with dissociation constants of 2.74 and 3.79 MUM respectively. Intriguingly, binding of Ni(2+) instead of Zn(2+) induces protein conformational changes around the active sites of the FKBP domain, implicating a regulatory role of nickel. The twin-arginine translocation (Tat) signal peptide from the small subunit of [NiFe] hydrogenase (HydA) binds the protein at the IF domain. Nickel binding and the recognition of the Tat signal peptide by the protein suggest that SlyD participates in [NiFe] hydrogenase maturation processes. PMID- 22045419 TI - A new cyclizidine analog-JBIR-102-from Saccharopolyspora sp. RL78 isolated from mangrove soil. PMID- 22045420 TI - Establishment of norvancomycin fluorescence polarization immunoassay for therapeutic drug monitoring. AB - To establish a rapid and simple fluorescence polarization immunoassay method for determination of norvancomycin serum concentration, we collected 300 serum samples from the patients receiving norvancomycin in the hospitals localized in Shanghai, China. The drug concentrations were measured by the established HPLC method and FPIA with vancomycin kit. A FPIA algorithm for the determination of norvancomycin concentration was established according to the correlation between the FPIA and HPLC results. The methods and algorithm were validated in another 70 clinical samples. HPLC determination showed a good linear correlation within the range of 0.5-100 mg l(-1) of norvancomycin concentrations. The method was validated via extraction recovery, intra- and inter-day methodological recovery and stability of norvancomycin in serum. Correlation analysis between the measurements of HPLC and FPIA in 300 serum samples gave the linear regression equation: (concentration by HPLC)=0.760 * (concentration by FPIA)-0.577 (P<0.001, R(2)=0.982). An algorithm was derived from this correlation for measuring the serum norvancomycin concentrations with FPIA. When it was validated in additional 70 serum samples from patients, 'FPIA algorithm' showed good accuracy versus HPLC: 'FPIA algorithm'=0.93 (HPLC)+0.63, R(2)=0.962, and 94.3% of the results from FPIA algorithm fell within the range of -20%/+20% of HPLC. This algorithm developed in this study can be easily used for determination of norvancomycin using TDx analyzer with vancomycin kit indirectly. It may also be useful for norvancomycin therapeutic drug monitoring. PMID- 22045422 TI - Current world literature. PMID- 22045424 TI - Phosphodiesterase 4 D gene polymorphism in relation to intracranial and extracranial atherosclerosis in ischemic stroke. AB - In ischemic stroke, extracranial MR angiography (ECMRA) is more frequently abnormal in Caucasians and intracranial (ICMRA) in Asians which may have a genetic basis. We report phosphodiesterase (PDE4D) gene polymorphism and its correlation with MRA findings in patients with ischemic stroke. Consecutive patients with MRI proven ischemic stroke undergoing MRA were included in this study. The severity of atherosclerotic stenosis on MRA was categorized into moderate 50%-80%, severe 80%-99%, and total occlusion 100% using NASCET criteria. The polymorphism in SNP 32, SNP 83 and SNP 87 of PDE4D gene was analyzed by PCR both in the patients and in 188 controls. Among the 148 patients, MRA was abnormal in 77% patients; ECMRA in 53.8%, ICMRA in 66% and both were abnormal in 42% patients. The frequency of CC genotype of PDE4D83 was significantly higher in the patients with ischemic stroke compared to controls (OR 3.38, 95% CI 1.61 7.11, P= 0.001). The frequency of TT genotype of PDE4D87 was significantly higher ICMRA abnormalities (20%) compared to normal ICMRA (2%). The genotype and allele frequency of PDE4D83 and PDE4D32 were not significantly related to MRA abnormalities. The role of PDE4D87 in atherosclerosis needs confirmation in larger studies. PMID- 22045425 TI - HLA and bronchopulmonary dysplasia susceptibility: a pilot study. AB - There is little data on the association between Human Leucocyte Antigen (HLA) alleles and Bronchopulmonary Dysplasia (BPD) of the preterm newborn. Our aim was to assess associations between HLA alleles and BPD susceptibility. We studied 156 preterm neonates (82 M/ 74 F) < 32 weeks gestational age, alive at 36 weeks gestational age. Detailed clinical data were collected. HLA typing was performed by PCR-SSO. HLA allele frequencies where determined by direct counting for BPD and no-BPD groups. Comparison between BPD and no BPD groups was performed using t test, chi2 test or Fisher exact test and logistic regression as appropriate. Relative risks (RR) and their 95% confidence intervals (95% CI) were also calculated as association measures. We diagnosed 56 (35.9%) neonates with mild BPD and 27 (17%) with moderate/ severe BPD. We found a significant association between HLA-DRB1*01 and mild BPD (OR=3.48[1.23-10.2]).The alleles HLA-A*24, A*68, -B*51,-Cw*07, -Cw*14, -Cw*15 and -DRB1*01 presented a significant association with moderate/ severe BPD. When adjusted to gestational age and birth weight HLA-A*68 (OR=5.41[1.46; 20.05]), -B*51 (OR=3.09[1.11; 8.63]) and -Cw*14 (OR=4.94[1.15; 21.25]) were significantly associated with moderate/ severe BPD. Conclusion - Our findings suggest an association between HLA-A*68, -B*51 and C*14 and BPD susceptibility, and that an autoimmune mechanism may be implicated in the pathogenesis of the disease. PMID- 22045426 TI - Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease. AB - BACKGROUND: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. SUBJECTS AND METHODS: We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and sex matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. RESULTS: Serum progranulin levels were significantly higher in NAFLD patients (34 +/- 13 ng/mL) than in controls (28 +/- 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (beta = 0.392; t = 2.226, P < 0.01). CONCLUSIONS: Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis. PMID- 22045427 TI - Absence of kl-vs variant of klotho gene in Iranian cardiac patients (comparison to the world populations). AB - OBJECTIVE: Klotho has an important role in development of coronary artery (CAD) disease. A functional variant of klotho gene (kl-vs) has been found as an independent risk factor for early-onset occult coronary artery disease (CAD) in previous studies. The Frequency of this variant was not known in Iranian population. We have examined the allele frequency of the kl-vs variant in a case control study in an Iranian population. METHODS AND RESULTS: Genotyping for kl-vs variant was carried out in N=107 individuals including N=54 cases and N=53 control who all underwent coronary angiogram for CAD evaluation. Patients with >50% stenosis in vessels considered as case groups (or CAD^{+}) and patients with normal vessels (or CAD^{ }) as controls. The frequency of kl-vs variant was determined in these patients using PCR-RFLP technique. None of the individual was carrying the kl-vs mutation in our samples. The frequency of kl-vs mutation was significantly different from previous studies in different populations. CONCLUSION: The kl-vs variant seems to be scare found in the Iranian population in comparison to other populations reported previously. Klotho gene might be a candidate gene of atherosclerosis in some populations but not in Iranian population. Further studies are required to examine the frequency of kl-vs variant in other populations from the Middle East. PMID- 22045428 TI - Association of endothelial dysfunction with endothelin, nitric oxide and eNOS Glu298Asp gene polymorphism in coronary artery disease. AB - The endothelial dysfunction has been implicated as a major event in the pathogenesis of atherosclerosis. Therefore, this study was planned to determine (a) role of endothelium-derived nitric oxide (NO) and endothelin as coronary artery disease (CAD) risk markers and (b) intergenotypic variation of endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism in CAD.The endothelin, NO and eNOS genotypes were determined in 60 patients with documented history of CAD. These were compared with 50 age- and sex- matched healthy controls. The genotype frequencies for eNOS gene polymorphism were determined by PCR and RFLP. The plasma endothelin in CAD patients was significantly higher (p< 0.001) whereas, the NO level in CAD group was significantly lower (p< 0.001) than the control group. The genotype frequencies for Glu298/Asp (Glu/Glu and Glu/Asp) genotypes were 75% and 25% in CAD subjects and 88% and 12% in control subjects, respectively. No Asp/Asp was found in any of the groups. The genotype frequencies differed significantly (p< 0.05) between the controls and cases. In conclusion, endothelin and NO may be used as markers of endothelial dysfunction in CAD. Asp allele might be a risk factor for CAD in the North Indian population. PMID- 22045429 TI - Polymorphism in the KCNA3 gene is associated with susceptibility to autoimmune pancreatitis in the Japanese population. AB - Autoimmune pancreatitis (AIP), characterized by irregular narrowing of the main pancreatic duct, swelling of the pancreas, and histological evidence of lymphoplasmacytic inflammation by high serum immunoglobulin G4, is distinct from ordinary pancreatitis. However, genetic factors involved in the etiology and pathophysiology of AIP remain unclear. Sixty-four patients with autoimmune pancreatitis (53 men, 11 women; mean age, 62.4 years) and 104 healthy Japanese controls were enrolled in this study. We performed an association analysis using 400 microsatellite markers with an average spacing of 10.8 cM in the genome. We also evaluated the association of AIP with seven single nucleotide polymorphisms (SNPs) within the 20-kb region around the potassium voltage-gated channel, shaker related subfamily, member 3 gene (KCNA3). We identified six statistically significant markers (D1S2726, D5S410, D6S460, D10S548, D15S128, and D20S186; P< 0.05) related to susceptibility. The surrounding region showing the strong association (P=7.4 * 10^{-7}, Pc=0.0015) contained the KCNA3 gene. Further analysis by SNP genotyping in KCNA3 gene revealed that four SNPs (rs2840381, rs1058184, rs2640480, rs1319782) were significantly associated with the AIP susceptibility (P< 0.007). KCNA3 is known to be involved in immunomodulation of autoreactive effector and memory T cell--mediated autoimmune diseases. Our findings provide the first evidence that KCNA3 is associated with AIP and suggest that KCNA3 may influence the risk for AIP. PMID- 22045430 TI - Human GST loci as markers of evolutionary forces: GSTO1*E155del and GSTO1*E208K polymorphisms may be under natural selection induced by environmental arsenic. AB - Over the last two decades, significant data has been accumulated linking Glutatione S-Transferases (GSTs) with the development of several diseases. Contemporary studies have demonstrated the impact of ethnicity on GST allele frequencies. The aim is to verify if the variability of GST genes reflects population demographic history or rather selective pressures. GST genes (GSTM1, GSTO1 GSTO2, GSTT1) were analysed in three Ecuadorian populations (Cayapas, n=114; Colorados, n=104; African-Ecuadorian, n=77) and compared with HapMap data. GST SNPs were determined using the PCR-RFLP method while GST null phenotype was determined using a Multiplex PCR. The population relationship achieved using GSTM1 positive/null, GSTO1*A140D, GSTO2*N142D and GSTT1 positive/null are in agreement with the data obtained using neutral polymorphisms: Amerindians are close to Asian populations and African-Ecuadorians to African populations. To what concerns GSTO1*del155 and GSTO1*K208 variants, allele frequencies never exceeded 10%, showing no significant differences in the Ecuadorian groups and in worldwide populations. The features of GSTO1*del155 and GSTO1*K208 variants and their association with arsenic biotransformation deficiency suggest the presence of a selection mechanism towards these loci. In particular, this hypothesis is strengthened by a possible linkage between these alleles and the susceptibility of arsenic-induced male infertility. PMID- 22045431 TI - A polymorphism within the connective tissue growth factor (CTGF) gene has no effect on non-invasive markers of beta-cell area and risk of type 2 diabetes. AB - Chromosomal locus 6q23 is strongly linked to type 2 diabetes (T2DM) and related features including insulin secretion in various ethnic populations. Connective tissue growth factor (CTGF) gene is an interesting T2DM candidate gene in this chromosome region. CTGF is a key mediator of progressive pancreatic fibrosis up regulated in type 2 diabetes. In contrast, CTGF inactivation in mice compromises islet cell proliferation during embryogenesis. The aim of our study was to investigate an impact of CTGF genetic variation on pancreatic beta-cell function and T2DM pathogenesis. We studied the effect of a common CTGF polymorphism rs9493150 on the risk of the T2DM development in three independent German cohorts. Specifically, the association between CTGF polymorphism and non-invasive markers of beta-cell area derived from oral glucose tolerance test was studied in subjects without diabetes. Neither in the Metabolic Syndrome Berlin Potsdam (MESYBEPO) study (n=1026) (OR=0.637, CI (0.387-1.050); p=0.077) nor in the European Prospective Investigation into Cancer and Nutrition-Potsdam (EPIC Potsdam) (n=3049) cohort (RR=0.77 CI (0.49-1.20), p=0.249 for the recessive homozygote in general model), a significant association with increased diabetes risk was observed. The risk allele of rs9493150 had also no effect on markers of beta-cell area in the combined analysis of the MESYBEPO and Tubingen Family Study (n=1826). In conclusion, the polymorphism rs9493150 in the 5'-untranslated region of the CTGF gene has no association with T2DM risk and surrogate markers of beta cell area. PMID- 22045432 TI - Amphiphilic star-block copolymers and supramolecular transformation of nanogel like micelles to nanovesicles. AB - Amphiphilic star-block copolymers based on poly(3-hydroxybutyrate) with adamantyl end-functionalization were synthesized via anionic ring-opening polymerization and alkyne-azide "Click Chemistry" coupling. In aqueous medium, the copolymers self-assembled into nanogel-like large compound micelles, and transformed into vesicular nanostructures under the direction of host-guest interaction between the adamantyl end and dimethyl-beta-cyclodextrin. PMID- 22045433 TI - Use of a novel technique, solid phase microextraction, to measure tranexamic acid in patients undergoing cardiac surgery. AB - PURPOSE: Solid phase microextraction (SPME) is a technique widely used and accepted in the field of food technology and in environmental and biological analyses. Despite its numerous advantages over older analytical methods, it has not been studied extensively in the medical sciences. Tranexamic acid (TXA) is currently the sole antifibrinolytic agent used during cardiac surgery involving the use of cardiopulmonary bypass (CPB). The current standard method of measuring TXA in plasma is based on plasma protein precipitation (PPP), but this analytical approach is time-consuming and not practical for routine use. The aim of the current study was to compare plasma TXA levels measured with the PPP method vs those acquired with the novel, highly efficient SPME technique. We also investigated the use of automated SPME with the aim of improving the technique so it could be used efficiently for measuring plasma TXA levels. METHODS: With Research Ethics Board approval, we undertook a prospective, investigator-blinded study in ten patients undergoing cardiac surgery with CPB. An initial TXA bolus of 30 mg.kg(-1) was infused over 15 min followed by a 16 mg.kg(-1).hr(-1) infusion until chest closure with a 2 mg.kg(-1) load in the pump prime. Each blood sample was divided into two portions and assigned a random number to blind the analyzing laboratory. The blood TXA concentration was measured using both PPP and SPME. Agreement between the two tests was analyzed using the Bland-Altman plot. RESULTS: Comparisons of plasma TXA concentrations measured with the two methods (PPP and SPME) showed good agreement. Absolute recovery of TXA for PPP was 64.9-78.2%; its precision, as a percentage of the relative standard deviation (RSD) was < 10% [with the exception of the lower limit of quantification (LLOQ), where the RSD was 18%]; and its accuracy, as the bias against the nominal concentration, was < 7% (for LLOQ it was 15%). Thus, extraction with SPME compared favourably with the PPP technique. CONCLUSIONS: Solid phase microextraction is a relatively simple, rapid extraction technique that can facilitate future pharmacokinetic studies analyzing TXA drug concentrations and drug dosing in various clinical settings. PMID- 22045434 TI - Incorporating sustainability into community-based healthcare practice. AB - There is now irrefutable evidence that climate change and increasing environmental degradation negatively affect population health. Healthcare plays an important role in addressing these emerging environmental challenges, considering its core aim is to protect and promote health. Preliminary research in Victoria, Australia, suggests that healthcare practitioners are endeavouring to factor in environmental concerns into their practice. Health promotion, an integral part of the healthcare system, is considered an area of practice that can support action on sustainability. Based on five qualitative case studies and key stakeholder interviews, this article explores key barriers and facilitators to incorporating sustainability into community-based healthcare practice. The findings demonstrate that despite multiple barriers, including funding and lack of policy direction, health promotion principles and practices can enable action on sustainability. PMID- 22045435 TI - Should we start prescribing omega-3 polyunsaturated fatty acids in chronic heart failure? AB - Chronic heart failure (HF) represents a significant health care burden. Over the past few decades, there have been considerable data supporting the benefits of omega-3 polyunsaturated fatty acids (PUFAs) on overall cardiovascular health. Reasons for the potential benefits of omega-3 PUFAs are multifactorial and not completely understood. It is likely that the culmination of multiple effects collectively help to prevent the development and slow the progression of chronic HF. A number of key epidemiologic and randomized trials have provided the basis of evidence in support of omega-3 PUFA supplementation in HF. This article reviews the benefits of omega-3 PUFAs and discusses the implications of recent trials. While the benefits seen in patients with chronic HF are modest at best, we believe the balance of evidence still favors the continuation of omega-3 PUFA supplementation in patients with chronic HF. PMID- 22045436 TI - Parallelism in constant comparison analysis. PMID- 22045437 TI - Modeling the effects of past relationship and obligation on changes in the health and health promotion of women caregivers of family members with dementia. AB - Wuest's (1998, 2001) caregiving theory was tested with 282 women self-identified as caregivers of family members with dementia to examine how quality of past relationship within caregiving dyads and sense of obligation to care affected their health outcomes and health promotion over 9 months, using latent growth curve analysis. The model explained 62% of the variance in women's health (Time 4). Health was affected positively by past relationship and negatively by obligation. Health promotion was positively affected by health (Time 1) and by obligation. Change observed in health promotion was nonlinear and positively affected health (Time 4). Findings suggest past relationship and obligation to care predict health outcomes for caregivers and that interventions to increase caregivers' health promotion may improve health outcomes. PMID- 22045442 TI - The role of collective action in enhancing communities' adaptive capacity to environmental risk: an exploration of two case studies from Asia. AB - BackgroundIn this paper we examine the role of collective action in assisting rural communities to cope with and adapt to environmental risks in Nepalgunj, Nepal and Krabi Province, Thailand. Drawing upon two case studies, we explore the role of collective action in building adaptive capacity, paying particular attention to the role of social networks.MethodsData for this paper was gathered using a range of different methods across the two different studies. In Nepal semi-structured interviews were conducted with a range of stakeholders in addition to participant observation and secondary data collection. In Thailand the researchers utilised a vulnerability assessment, participatory multi stakeholder assessment, a detailed case study and an online dialogue. FindingsWe make three key observations: firstly, collective action plays a significant role in enhancing adaptive capacity and hence should be more strongly considered in the development of climate change adaptation strategies; secondly, social networks are a particularly important component of collective action for the building of adaptive capacity; and thirdly, the mandate, capacity, and structure of local government agencies can influence the effectiveness of collective action, both positively and negatively.Conclusions We argue that there is an urgent need for further consideration of the different forms of collective action within community-based disaster risk management and climate change adaptation. PMID- 22045443 TI - Long- and short-term plastic modeling of action prediction abilities in volleyball. AB - Athletes show superior abilities not only in executing complex actions, but also in anticipating others' moves. Here, we explored how visual and motor experiences contribute to forge elite action prediction abilities in volleyball players. Both adult athletes and supporters were more accurate than novices in predicting the fate of volleyball floating services by viewing the initial ball trajectory, while only athletes could base their predictions on body kinematics. Importantly, adolescents assigned to physical practice training improved their ability to predict the fate of the actions by reading body kinematics, while those assigned to the observational practice training improved only in understanding the ball trajectory. The results suggest that physical and observational practice might provide complementary and mutually reinforcing contributions to the superior perceptual abilities of elite athletes. Moreover, direct motor experience is required to establish novel perceptuo-motor representations that are used to predict others' actions ahead of realization. PMID- 22045446 TI - Long-term outcomes of patients treated with primary stenting for transplant renal artery stenosis: a 10-year case cohort study. AB - BACKGROUND: The purpose of the present study was to evaluate graft and patient survival and long-term outcomes of primary endoluminal stenting (PES) as an initial treatment for transplant renal artery stenosis (TRAS). METHODS: From December 1999 to March 2010, 744 consecutive patients undergoing renal transplantation were enrolled. Patients were divided into one of two groups: the study group, comprised of 18 patients who underwent PES for TRAS > 60%, and a control group, including the remaining 726 recipients who did not develop TRAS post-transplantation. Primary outcome measures were death-censored graft failure and all-cause mortality. The immediate and long-term effects of PES were evaluated by assessing blood pressure (BP) control and biochemical graft function. RESULTS: The technical success rate for PES was 100%, and minor complication occurred in only one case (5.6% of the study group). With a mean follow-up of 7.1 +/- 3.7 and 6.9 +/- 2.4 years in the study and control groups, respectively, 4 patients in the study group and 113 patients in the control group reached the primary outcome (log rank P = 0.418). The reduction in stenosis resulted in immediate improvement in BP control and graft function, which persisted throughout the 6 year follow-up period. Restenosis occurred in only one patient (5.6%), but restenosis was not the cause of graft failure. CONCLUSIONS: This study indicated that both the long-term graft and patient survival were as good in TRAS patients treated with PES as in patients without TRAS. The data also supported the use of PES as an initial treatment for TRAS. PMID- 22045447 TI - Impact of preoperative thrombocytosis on the survival of patients with primary colorectal cancer. AB - BACKGROUND: Although thrombocytosis has been reported in patients with various types of cancer, the association between thrombocytosis and the clinicopathological features of patients with colorectal cancer (CRC) has not been fully investigated. We evaluated the clinical features associated with thrombocytosis in CRC. MATERIALS AND METHODS: The medical records of 636 consecutive CRC patients undergoing surgery in our department between January 2002 and July 2008 were retrospectively reviewed. The correlation between the clinicopathological variables and the preoperative platelet count was analyzed by univariate and multivariate analyses. The impact of thrombocytosis on the prognosis of these patients was assessed, in comparison with the other clinicopathological variables. RESULTS: Platelet count showed significant correlation with gender, age, venous involvement, tumor size, depth of invasion, regional lymph node metastasis, distant metastasis in univariate analysis, and tumor size and depth of invasion were independent factors in multivariate analysis. The cancer-specific survival (CSS) of CRC patients with thrombocytosis was significantly shorter than that for those without thrombocytosis (P < 0.001), specifically in patients with stage III CRC (P < 0.001). Multivariate analysis indicated that thrombocytosis was an independent prognostic factor of CSS (hazard ratio = 2.96, 95% confidence interval [CI] = 1.72-5.00). Moreover, within stage II CRC, the univariate analysis revealed that disease-free survival (DFS) was associated with preoperative thrombocytosis, but not the other clinicopathological variables. CONCLUSIONS: Preoperative thrombocytosis is not only an independent indicator of poor CSS in CRC patients but also an independent predictor of poor DFS in patients with stage II CRC. PMID- 22045448 TI - How to avoid postoperative liver failure: a novel method. AB - BACKGROUND: Postoperative liver failure (PLF) is the most feared and severe complication after extensive liver resections. METHODS: We present an innovative surgical technique that has been employed for the treatment of three patients (two with multiple colorectal liver metastases and one with hilar cholangiocarcinoma) whose livers were previously considered locally unresectable because of an insufficient future liver remnant (FLR). In-situ liver transection with right portal vein ligation was implemented. RESULTS: Six days after surgery a volumetric computed tomography (CT)-scan showed 40-80% hypertrophy of the FLR. The patients then underwent a completion surgery with right hepatectomy or right trisectionectomy. None of the patients developed PLF during a mean hospital stay of 16 days. After a mean follow-up of two months, the three of them are free of disease. CONCLUSIONS: This technique induced rapid growth of the FLR, greater than that reported with portal vein occlusion alone. It represents a promising advance in oncological liver surgery that readdresses the current management of patients with primarily unresectable liver disease. Such a revolutionary strategy allows a two-stage surgical approach during a single hospital stay and without PLF. However, further research is needed to determine the long-term outcomes of this technique and to explain the occurrence of such enhanced liver regeneration. PMID- 22045450 TI - Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ): a patient-based evaluation tool for hip-joint disease. The Subcommittee on Hip Disease Evaluation of the Clinical Outcome Committee of the Japanese Orthopaedic Association. AB - BACKGROUND: The Japanese Orthopaedic Association Hip Score is widely used in Japan, but this tool is designed to reflect the viewpoint of health-care providers rather than that of patients. In gauging the effect of medical therapies in addition to clinical results, it is necessary to assess quality of life (QOL) from the viewpoint of patients. However, there is no tool evaluating QOL for Japanese patients with hip-joint disease. METHODS: With the aim of more accurately classifying QOL for Japanese patients with hip-joint disease, we prepared a questionnaire with 58 items for the survey derived from 464 opinions obtained from approximately 100 Japanese patients with hip-joint disease and previously devised evaluation criteria. In the survey, we collected information on 501 cases, and 402 were subjected to factor analysis. From this, we formulated three categories-movement, mental, and pain-each comprising 7 items, for a total of 21 items to be used as evaluation criteria for hip-joint function. RESULTS: The Cronbach's alpha coefficients for the three categories were 0.93, 0.93, and 0.95, respectively, indicating the high reliability of the evaluation criteria. The 21 items included some related to the Asian lifestyle, such as use of a Japanese-style toilet and rising from the floor, which are not included in other evaluation tools. CONCLUSIONS: This self-administered questionnaire may become a useful tool in the evaluation of not only Japanese patients, but also of members of other ethnic groups who engage in deep flexion of the hip joint during daily activities. PMID- 22045451 TI - Femoral metaphysis bending test of rat: introduction and validation of a novel biomechanical testing protocol for osteoporosis. AB - BACKGROUND: The diaphysis bending test is generally accepted to assess the biomechanical properties of bone in osteoporotic animals. However, bone strength loss was more pronounced at the metaphysis than diaphysis. Therefore, the biomechanical test should be focused on the metaphysis. This study aimed to validate a novel biomechanical test for femoral metaphysis in ovariectomized rats. METHODS: Twenty 5-month-old female Sprague-Dawley rats were randomly divided into the ovariectomized (OVX) and sham-operated (Sham) groups. Examination of femur bone mineral density (BMD) and histomorphometry of the distal femur were performed. Femur biomechanical parameters (maximal load, yield load, and stiffness) were determined by the diaphysis bending test and a novel designed metaphysis bending test. Pearson's correlations were used to analyze the relationships between the biomechanical parameters and BMD or bone histomorphometry indexes (%Tb.Ar, Tb.N, Tb.Th), respectively. RESULTS: The femur BMD, bone histomorphometry indexes, and biomechanical parameters of OVX were inferior to those of the Sham group (P < 0.05). In the diaphysis bending test, the mean difference of the maximum load and yield load between the OVX and Sham groups were 13.83 +/- 5.27 and 15.69 +/- 4.15 N, which were significantly lower than in the metaphysis bending test (43.34 +/- 4.27, 48.90 +/- 4.35 N; all P < 0.05). Positive correlations between biomechanical parameters and femur BMD or bone histomorphometry indexes were observed in both the diaphysis bending and metaphysis bending test. The biomechanical parameters in the metaphysis bending test showed stronger correlations with BMD and bone histomorphometry indexes. CONCLUSIONS: The femoral metaphysis bending test was validated to assess osteoporosis in our study, and it was more sensitive than the diaphysis bending test in evaluating the change of biomechanical properties of the femur in osteoporotic rats. PMID- 22045453 TI - [Diabetes remission in cats: a review]. AB - Remission from diabetes is seen in 25 - 50 % of cats during the first months of therapy. The likelihood of remission is higher in old cats and cats with normal cholesterol than in young cats and cats with increased cholesterol. The results of an ongoing study indicate that initial intravenous insulin therapy has positive effects on remission rates and quality of metabolic control. PMID- 22045454 TI - [FeLV infection in the cat: clinically relevant aspects]. AB - The feline leukemia virus (FeLV) is a retrovirus of the domestic cat that was described almost 50 years ago. The FeLV-infection may lead to fatal diseases in domestic and small wild cats. The use of efficacious diagnostics assays and vaccines led to a reduction of the FeLV prevalence; however, FeLV still poses a problem for the cat presented with the infection. This article aims to describe recent developments in diagnostics and findings in the infection pathogenesis that are clinically relevant. PMID- 22045452 TI - Usefulness of combining intermittent hypoxia and physical exercise in the treatment of obesity. AB - Obesity is an important public health problem worldwide and is a major risk factor for a number of chronic diseases such as type II diabetes, adverse cardiovascular events and metabolic syndrome-related features. Different treatments have been applied to tackle body fat accumulation and its associated clinical manifestations. Often, relevant weight loss is achieved during the first 6 months under different dietary treatments. From this point, a plateau is reached, and a gradual recovery of the lost weight may occur. Therefore, new research approaches are being investigated to assure weight maintenance. Pioneering investigations have reported that oxygen variations in organic systems may produce changes in body composition. Possible applications of intermittent hypoxia to promote health and in various pathophysiological states have been reported. The hypoxic stimulus in addition to diet and exercise can be an interesting approach to lose weight, by inducing higher basal noradrenalin levels and other metabolic changes whose mechanisms are still unclear. Indeed, hypoxic situations increase the diameter of arterioles, produce peripheral vasodilatation and decrease arterial blood pressure. Furthermore, hypoxic training increases the activity of glycolytic enzymes, enhancing the number of mitochondria and glucose transporter GLUT-4 levels as well as improving insulin sensitivity. Moreover, hypoxia increases blood serotonin and decreases leptin levels while appetite is suppressed. These observations allow consideration of the hypothesis that intermittent hypoxia induces fat loss and may ameliorate cardiovascular health, which might be of interest for the treatment of obesity. This new strategy may be useful and practical for clinical applications in obese patients. PMID- 22045455 TI - [Placement of intraluminal stents for treating tracheal collapse in dogs]. AB - Tracheal collapse is a progressive disease particularly of small breed dogs. In the terminal stage, when dyspnea becomes the dominating sign and is no longer manageable with medical treatment, a surgical procedure is necessary. With increasing frequency intraluminal tracheal stents are implanted minimal invasively. In individual animals this is a lifesaving procedure, leading to immediate elimination of dyspnea. In most dogs cough for some time has to be anticipated as the stent acts as a foreign body, but severe complications like excessive formation of granulation tissue, stent migration or stent fracture are rare. Stents represent an attractive treatment modality for tracheal collapse in dogs with dyspnea. PMID- 22045456 TI - In vivo induction of interferon gamma expression in grey horses with metastatic melanoma resulting from direct injection of plasmid DNA coding for equine interleukin 12. AB - Whole blood pharmacokinetics of intratumourally injected naked plasmid DNA coding for equine Interleukin 12 (IL-12) was assessed as a means of in vivo gene transfer in the treatment of melanoma in grey horses. The expression of induced interferon gamma (IFN-g) was evaluated in order to determine the pharmacodynamic properties of in vivo gene transduction. Seven grey horses bearing melanoma were injected intratumourally with 250 ug naked plasmid DNA coding for IL-12. Peripheral blood and biopsies from the injection site were taken at 13 time points until day 14 post injection (p.i.). Samples were analysed using quantitative real-time PCR. Plasmid DNA was quantified in blood samples and mRNA expression for IFN-g in tissue samples. Plasmid DNA showed fast elimination kinetics with more than 99 % of the plasmid disappearing within 36 hours. IFN-g expression increased quickly after IL-12 plasmid injection, but varied between individual horses. Intratumoural injection of plasmid DNA is a feasible method for inducing transgene expression in vivo. Biological activity of the transgene IL-12 was confirmed by measuring expression of IFN-g. PMID- 22045457 TI - A long life among ruminants: giraffids and other special cases. AB - In order to investigate differences in the relative maximum longevity and other life history parameter between ruminant species, we collated data on mean body mass, maximum longevity, gestation period and newborn mass in wild ruminant and camelid species. Among ruminants, giraffids (giraffe Giraffa camelopardalis and okapi Okapia johnstoni) have particularly high longevities, long gestation periods, and low intrauterine growth rates. A particularly high absolute and relative longevity is also achieved by the anoa (Bubalus depressicornis), a member of the bovinae (cattle-type ruminants) and an insular dwarf (inhabiting the Indonesian island of Sulawesi). The fact that some (but not all) other small ruminants also achieve surprisingly high longevities leads to the hypothesis that extreme relative longevities in this group are an indication for secondary body size reduction. PMID- 22045458 TI - [Bursitis with severe tendon and muscle necrosis on the lateral stifle area in cattle]. AB - In 21 animals, chronic swelling on the lateral aspect of the stifle also known as "perigonitis", "stable-syndrome" or "bursitis bicipitalis femoris" were evaluated. Ultrasonography showed increased fluid in the distal subtendinous bursa of the biceps femoris muscle and structural changes in the tendons, muscles, subcutis and fasciae. Soft tissue swelling and an irregular contour of the lateral tibial condyle were typical signs on radiographs. Macroscopic changes were found at the insertion of the biceps femoris muscle, the distal subtendinous bursa of the biceps femoris muscle, the lateral collateral ligament of the stifle, the origin of muscles on the lateral femoral condyle and the lateral tibial condyle. They mainly consisted of tendon and muscle tissue necrosis with granulation tissue. Histology revealed areas of coagulation necrosis in tendons and ligaments, in which occasionally Onchocerca spp. were seen. The severity of lesions correlated well with the clinical signs, which were associated with a poor prognosis in advanced cases. PMID- 22045459 TI - [Polychondritis: a new disease in Swiss Braunvieh?]. AB - Over the last 10 years Swiss Braunvieh cattle with malformations of the pinnae have repeatedly been reported. Endoscopy revealed a shortened and thickened epiglottis and malformations of the arytenoid cartilage in some of these animals. In most cases the elastic cartilage was replaced by fibrocartilage and hyaline cartilage. The direct cause and pathogenesis of the malformations could not be determined. PMID- 22045461 TI - [Dogs in the workplace]. PMID- 22045464 TI - The value of palliative gastrectomy in gastric cancer with distant metastasis. AB - PURPOSE: The purpose of this study was to examine the value of surgical resection and to find prognostic factors for metastatic gastric cancer. METHODS: Clinicopathological data of 257 cM1 gastric cancer patients who underwent an operation at Seoul National University Hospital from January 1999 to December 2004 were reviewed. Patients were grouped into the resection (RS, n=165) and nonresection groups (NR, n=92). To evaluate whether there was any selection bias, patients were stratified according to chemotherapy and preoperative CT findings were compared. RESULTS: There were no significant differences in clinicopathologic features and preoperative CT findings between the RS and NR groups. For chemotherapy, the RS group had a survival benefit (median survival; 12.7 vs. 11.2 months, p=0.0107). In the subanalysis, there was a survival benefit to the RS group when metastasis was confined to one site (14 vs. 9.7 months, p=0.04). In patients with no chemotherapy, the RS group had no benefit (p=0.151). In univariate and multivariate analyses, resection (p=0.001), chemotherapy (p<0.001), the number of organs with metastatic lesions (p=0.003), and elective operation (p<0.001) were significant prognostic factors. CONCLUSIONS: This retrospective study suggests that surgical resection in metastatic gastric cancer may improve survival when combined with chemotherapy, especially when metastasis is confined to one site. PMID- 22045465 TI - Pathologic nonresponders after neoadjuvant chemoradiation for esophageal cancer demonstrate no survival benefit compared with patients treated with primary esophagectomy. AB - BACKGROUND: Neoadjuvant chemoradiation (NCRT) has become the preferred treatment for patients with locally advanced esophageal cancer. Survival often is correlated to degree of pathologic response; however, outcomes in patients who are found to be pathologic nonresponders (pNR) remain uninvestigated. This study was designed to evaluate survival in pNR to NCRT compared with patients treated with primary esophagectomy (PE). METHODS: Using our comprehensive esophageal cancer database, we identified patients treated with NCRT and deemed pNR along with patients who proceeded to PE. Clinical and pathologic data were compared using Fisher's exact and chi(2), whereas Kaplan-Meier estimates were used for survival analysis. RESULTS: We identified 63 patients treated with NCRT and were found to have a pNR, and 81 patients who underwent PE. Disease-free (DFS) and overall survival (OS) were significantly decreased in the pNR group compared with those treated with PE (10 vs. 50 months (0-152), P < 0.001 and 13 vs. 50 months (0-152), P < 0.001, respectively). For patients with stage II disease, DFS and OS were similarly decreased in pathologic nonresponders (13 vs. 62 months (0-120), P < 0.001 and 31 vs. 62 months (0-120), P = 0.024, respectively). There were no differences in DFS or OS for patients with stage III disease (10 vs. 14 months (0 152), P = 0.29 and 10 vs. 19 months (0-152), P = 0.16, respectively). CONCLUSIONS: Pathologic nonresponders to NCRT for esophageal cancer receive no benefit in DFS or OS compared with patients treated with PE. For patients with stage II disease, DFS and OS are, in fact, significantly decreased in the pNR. PMID- 22045466 TI - Feasibility of robot-assisted neck dissections via a transaxillary and retroauricular ("TARA") approach in head and neck cancer: preliminary results. AB - BACKGROUND: Recently, robot-assisted neck dissection in thyroid cancer patients with lateral neck node metastasis has been demonstrated to be feasible. We realized the necessity of technical modification in order to apply robotic system to comprehensive neck dissection for head and neck squamous cell carcinoma. This study examined the feasibility and safety of transaxillary and retroauricular ("TARA") approach for robotic neck dissection in patients with head and neck squamous cell cancer. METHODS: Four human cadaveric dissections were followed by robotic neck dissections in seven patients with oral cavity or laryngopharyngeal cancer through TARA incision. RESULTS: In all cases, vital structures including major vessels and nerves were preserved. The numbers of retrieved lymph nodes in robotic neck dissections were comparable with those in conventional neck dissections. CONCLUSIONS: Robotic neck dissection via TARA approach is a feasible and useful method with excellent cosmetic results for treating nodal metastasis in selected cases of head and neck squamous cell cancer. PMID- 22045467 TI - Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy. AB - BACKGROUND: Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. METHODS: A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier method. RESULTS: A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. CONCLUSIONS: Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered. PMID- 22045468 TI - Risk factors for bronchopleural fistula after right pneumonectomy: does eliminating the stump diverticulum provide protection? AB - PURPOSE: Bronchopleural fistula (BPF) remains an important source of morbidity and mortality after right pneumonectomy. We reviewed our 18-year institutional experience with right pneumonectomy to identify risks factors for BPF. METHODS: From 1992 to 2010, a total of 145 patients who underwent right pneumonectomy were identified from an institutional database. Median age was 56 years. Most patients (66.2%) underwent surgery for non-small cell lung cancer. Sixty-seven patients (46.2%) received either chemotherapy or radiotherapy before surgery. Medical records were reviewed for 14 variables potentially predictive for BPF, including two airway closure techniques (standard bronchial closure and carinal closure). Variables predictive of BPF by univariate analysis were entered into a logistic regression model. RESULTS: The overall mortality rate was 13.1% (n=19), with 15.9 and 10.5% mortality in the bronchial closure and carinal closure groups, respectively (P=0.33). The overall BPF rate was 7.6% (n=11), with a 3.9% (3 of 76) rate in the carinal closure group compared to 11.6% (8 of 69) in the bronchial closure group (P=0.08). Seven of eight bronchial closure patients who developed BPF required operative repair. Only one of three patients who developed BPF after carinal closure did not spontaneously heal after open drainage. Multivariate analysis identified preoperative radiation dose (P=0.042) and bronchial closure (P=0.041) as independent risk factors for BPF, while the length of postoperative ventilation before development of BPF approached significance (P=0.057). CONCLUSIONS: In our experience, higher preoperative radiation doses are a risk factor for BPF after right pneumonectomy, while carinal closure exerts a protective effect. PMID- 22045470 TI - Implications of changes in plasma asymmetric dimethylarginine during treatment of hypertension. PMID- 22045469 TI - Synthesis of some new s-alkylated 1,2,4-triazoles, their mannich bases and their biological activities. AB - A series of 1-(4-methoxyphenyl)-2-[5-{(biphenyl-4-yloxy)methyl}4-(substituted phenyl)-3-mercapto-(4H)-1,2,4-triazol-3-ylthio)] ethanones (6a-6s) and 4 (substituted phenyl)-3-(morpholin/pyrrolidin-4-ylmethylthio)-5-(4 phenylphenoxymethyl)-4H-1,2,4-triazoles (7a-7e) were synthesized in order to obtain new compounds with potent anti-inflammatory and analgesic activity with insignificant ulceration. Among the synthesized compounds, (6c), (6e), (6g) and (6l) from triazole series and (7b) and (7e) from Mannich base series were found to exhibit significant anti-inflammatory activity with 59.69, 59.69, 64.69, 79.84, 54.54, 79.69% and 52.55, 57.50, 72.52, 83.03, 60.06, 84.08% inhibition of paw edema at 3 h and 5 h respectively, in comparison to the standard drug ibuprofen (78.93 and 82.58% at 3 h and 5 h). The active compounds were further tested for their analgesic activity and gastric ulceration study. Compounds 6g, 7b and 7e exhibited significant analgesic activity with reaction time (3.60, 3.22, 3.88 s) respectively at 60 min. without causing any gastric irritation. These compounds were also screened for their in vitro antimicrobial activity, Compounds 6f, 6g, 6h, 6l, 6o, 6p, 7a, 7b and 7c showed significant zone of inhibition against various antimicrobial stains. It is concluded that the compounds 6g, 7b and 7e possess a good spectrum of activities. Compound 7e may be considered potent for development of better anti-inflammatory agent. The antimicrobial activity revealed that most of the compounds showed moderate to significant activity. Compounds containing nitro, chloro, bromo and fluoro group showing better activity. All the compounds from 7a, 7b and 7e were active against gram positive bacteria (S. aureus). PMID- 22045471 TI - Determinants of influenza vaccination among young children in an inner-city community. AB - Few studies have examined potential factors that contribute to low influenza vaccination rates among minority children. This study aimed to assess the prevalence of early childhood influenza vaccination among young black and Latino children, living in inner-city neighborhoods, and examine the effects of child, caregiver and health system factors. Secondary data analysis was performed using a survey about medical home experiences conducted from May 2007-June 2008. The study sample was limited to children >=6 months in any influenza season prior to the 2006-2007 influenza season. Bivariate analyses and multivariable logistic regression tested associations between influenza vaccination receipt and socio demographic and health system characteristics. One-third of children received an influenza vaccination by the end of 2006-2007 season, while only 11% received a vaccination within their first season of eligibility. Black children were more likely than Latino children to have been vaccinated (50% vs. 31%, P<0.01) during their first few eligible seasons. Children whose mothers were older, proficient in English, and frequent users of healthcare were more likely to obtain vaccination. Child attendance at healthcare settings with immunization reminder systems was also positively correlated with influenza vaccination. Our findings suggest that initial vaccination receipt among minority children from inner-city communities might be improved by expanded influenza promotion activities targeting younger mothers or those with limited English proficiency. Strategies to increase the frequency of child's actual contact with the medical home, such as reminder systems, may be useful in improving uptake of influenza vaccination among inner-city, minority children. PMID- 22045472 TI - VEGF gene alternative splicing: pro- and anti-angiogenic isoforms in cancer. AB - Tumor growth and progression depend on angiogenesis, a process of new blood vessels formation from a preexisting vascular endothelium. Tumors promote angiogenesis by secreting or activating angiogenic factors that stimulate endothelial proliferation and migration and capillary morphogenesis. The newly formed blood vessels provide nutrients and oxygen to the tumor, increasing its growth. Thus, angiogenesis plays a key role in cancer progression and development of metastases. An important growth factor that promotes angiogenesis and participates in a variety of physiological and pathological processes is the vascular endothelial growth factor (VEGF-A or VEGF). Overexpression of VEGF results in increased angiogenesis in normal and pathological conditions. The existence of an alternative site of splicing at the 3' untranslated region of the mRNA results in the expression of isoforms with a C-terminal region which are downregulated in tumors and may have differential inhibitory effects. This suggests that control of splicing can be an important regulatory mechanism of angiogenesis in cancer. PMID- 22045476 TI - Mediastinal lymph node uptake in patients with prostate carcinoma on F18-choline PET/CT. AB - SUMMARY: Fluorine-18-methyl-choline (F18-choline) PET/computed tomography (CT) is routinely performed in our hospital for patients with significantly increased or rapidly increasing prostate-specific antigen (PSA) levels to detect and localize recurrent prostate carcinoma. We observed uptake of this PET tracer in mediastinal lymph nodes in a significant number of patients. The aim of this study was to assess the frequency of this finding and to determine whether it is correlated with tumour and nontumour-related aspects. MATERIALS AND METHODS: A total of 48 consecutive men (mean age: 65.6 years; range: 50-79 years, standard deviation: 7.1) with histopathologically proven prostate cancer were referred for F18-choline PET/CT imaging for restaging from March 2009 to October 2010. All patients had a suspicion of tumour recurrence because of an increased PSA or a rapidly increasing PSA. All studies were reviewed, and the results were correlated with general data such as age; smoking; chronic obstructive pulmonary disease; tumor, lymph nodes and distant metastases stage; Gleason Score and PSA level; with a maximum interval of 3 months between serum PSA and the PET/CT scan. RESULTS: In 27 patients (56.3%), F18-choline PET/CT showed positive lymph nodes in the mediastinum (mean standardized uptake values: 3.75; range: 1.7-13.8, standard deviation: 2.4). No histological biopsy was carried out in F18-choline positive lymph nodes, but in none of the patients was mediastinal recurrence or pulmonary infection observed during a 6-month follow-up. Only one patient had histologically proven pulmonary metastasis. No significant relationship was observed between mediastinal F18-choline lymph node uptake and serum PSA level (P=0.785), initial T stage (P=0.555), N stage (P=0.548), M stage (P=0.426), smoking (P=0.537), chronic obstructive pulmonary disease (P=0.115) or the presence of tumour recurrence on F18-choline PET/CT. CONCLUSION: Mediastinal lymph node uptake of F18 choline is frequently observed, without any significant relationship with tumour characteristics. Therefore, interpretation of positive mediastinal lymph node uptake should be done carefully. PMID- 22045477 TI - Prediction of functional recovery after revascularization in patients with chronic ischemic myocardial dysfunction: perfusable tissue index by positron emission tomography and contrast-enhanced MRI comparison study. AB - OBJECTIVES: In patients with chronic ischemic myocardial dysfunction, perfusable tissue index (PTI) obtained with positron emission tomography using oxygen-15 labeled water and carbon monoxide as tracers is inversely related to the extent of myocardial scar (nonperfusable tissue). Delayed contrast-enhanced (DCE) magnetic resonance imaging (MRI) accurately depicts the regional extent of myocardial fibrosis and predicts functional recovery after revascularization in patients with ischemic cardiomyopathy. Our aim was to compare PTI as a viability marker with DCE MRI. METHODS: Fourteen patients with ischemic left ventricular dysfunction were studied with positron emission tomography, using oxygen-15 labeled water and carbon monoxide as tracers, and with contrast-enhanced MRI. RESULTS: Functional improvement occurred in 38 of initially dysfunctional, revascularized segments (56%). Mean PTI was 1.04 +/- 0.20 in the improved segments versus 0.85 +/- 0.21 in the group without functional improvement (P<0.001). The areas under the receiver operator characteristics curves of PTI and DCE MRI were 0.7 and 0.74, respectively (P=not significant). Cutoff value of 25% DCE allowed correct identification of 82% segments with reversible dysfunction and 64% segments without reversible dysfunction. A threshold of 0.89 for PTI yielded the best diagnostic accuracy with sensitivity and specificity values of 76 and 54%, respectively. CONCLUSION: PTI can identify viable myocardium and predict improvement in regional function after revascularization in patients with chronic ischemic left ventricular dysfunction. Its diagnostic accuracy is comparable with that of DCE MRI. PMID- 22045479 TI - Weight loss and rapid cognitive decline in community-dwelling patients with Alzheimer's disease. AB - Weight loss is a frequent complication of Alzheimer's disease (AD) and a strong predictor of adverse outcomes in patients suffering from this disease. The aim of this study was to determine whether weight loss was a predictor of rapid cognitive decline (RCD) in AD. Four hundred fourteen community-dwelling ambulatory patients with a diagnosis of probable AD and a Mini-Mental State Examination (MMSE) score between 10 and 26 from the REAL.FR (REseau sur la maladie d'ALzheimer FRancais) cohort were studied and followed up during 4 years. Patients were classified in 2 groups according to weight loss defined by a loss of 4% or more during the first year of follow-up. RCD was defined as the loss of 3 points or more in MMSE over 6 months. The incidence of RCD was determined among both groups over the last 3 years of follow-up. MMSE, Katz's Activity of Daily Living scale, Mini-Nutritional Assessment scale, co-morbidities, behavioral and psychological symptoms of dementia, medication, level of education, living arrangement, and caregiver's burden were assessed every 6 months. Eighty-seven patients (21.0%) lost 4% or more of their initial weight during the first year. The incidence of RCD for all patients was 57.6 (95% confidence interval (CI) = 51.6-64.8) per 100 person-year (median follow-up of 15.1 months). In Cox proportional hazards models, after controlling for potential confounders, weight loss was a significant predictor factor of RCD (adjusted hazard ratio (HR) = 1.50, 95% CI = 1.04-2.17). In conclusion, weight loss predicted RCD in this cohort. Whether the prevention of weight loss (by improving nutritional status) impacts cognitive decline remains an open question. PMID- 22045481 TI - 39-week toxicity and toxicokinetic study of ponezumab (PF-04360365) in cynomolgus monkeys with 12-week recovery period. AB - Ponezumab (PF-04360365) is a novel humanized IgG2Deltaa monoclonal antibody that binds to amyloid-beta (Abeta). It is designed to have reduced immune effector function compared to other passive immunotherapies for Alzheimer's disease (AD). Toxicity was evaluated in cynomolgus monkeys treated intravenously with vehicle or 10, 30, or 100 mg/kg of ponezumab every 10th day for up to 39 weeks, and after a 12-week recovery phase. The Abeta peptide sequence of monkeys is identical to that of humans. No substantial difference in test article exposure between sexes was observed, and mean plasma Cmax and AUC0-n were approximately dose proportional. Ponezumab was detectable approximately 9 weeks after cessation of dosing. All animals, except two males given 10 mg/kg, maintained exposure to test article. One of these males tested positive for anti-ponezumab antibodies. Ponezumab was detected in the cerebrospinal fluid (CSF) of animals given active treatment. The estimated CSF/plasma ponezumab concentration ratio was <0.008 after multiple doses. At the end of the dosing and recovery phases, plasma Abeta1 40 and Abeta1-x were increased in treated animals versus controls. No test article-related effects were seen after ophthalmogical, cardiovascular, physical examinations, and clinical and anatomic pathology evaluations. Plasma concentrations of ponezumab on day 261 at the no observed adverse effect level of 100 mg/kg were 22.4 and 5.3 times greater on a Cmax and AUC basis, respectively, than human exposures at the highest dose (10 mg/kg) in a single-dose Phase I trial. These data suggest an acceptable safety profile for ponezumab as an immunotherapy for AD. PMID- 22045480 TI - Metabolic reserve as a determinant of cognitive aging. AB - Mild cognitive impairment (MCI) and Alzheimer's disease (AD) represent points on a continuum of cognitive performance in aged populations. Cognition may be impaired or preserved in the context of brain aging. One theory to account for memory maintenance in the context of extensive pathology involves 'cognitive reserve', or the ability to compensate for neuropathology through greater recruitment of remaining neurons. In this review, we propose a complementary hypothesis of 'metabolic reserve', where a brain with high metabolic reserve is characterized by the presence of neuronal circuits that respond adaptively to perturbations in cellular and somatic energy metabolism and thereby protects against declining cognition. Lifestyle determinants of metabolic reserve, such as exercise, reduced caloric intake, and intake of specific dietary components can promote neuroprotection, while pathological states arising from sedentary lifestyles and excessive caloric intake contribute to neuronal endangerment. This bidirectional relationship between metabolism and cognition may be mediated by alterations in central insulin and neurotrophic factor signaling and glucose metabolism, with downstream consequences for accumulation of amyloid-beta and hyperphosphorylated tau. The metabolic reserve hypothesis is supported by epidemiological findings and the spectrum of individual cognitive trajectories during aging, with additional data from animal models identifying potential mechanisms for this relationship. Identification of biomarkers for metabolic reserve could assist in generating a predictive model for the likelihood of cognitive decline with aging. PMID- 22045482 TI - Chronic mild stress accelerates the onset and progression of the Alzheimer's disease phenotype in Tg2576 mice. AB - The etiology of the more common (sporadic) forms of Alzheimer's disease (AD) remains unknown, although age is the most important risk factor. Nevertheless, interactions between environmental risk factors and genetic background may also influence the onset and progression of sporadic AD. Chronic stress, associated with altered memory and other neurological processes, is thought to influence the pathogenesis of AD. Hence, we evaluated the effect of unpredictable and consecutive chronic mild stressors on the onset of an AD-related pathology in the Tg2576 mouse line that overexpresses the human amyloid-beta protein precursor with the Swedish mutation (hAbetaPP(Swe)). Two months after exposure to chronic mild stress, 4 month-old animals that normally display no pathological features of AD, not only expressed pathological markers but also experienced cognitive dysfunction in the Morris water maze test. These findings suggest that chronic mild stress accelerates the onset of cognitive impairment and produces an increase in hippocampal amyloid-beta and phospho-tau levels on a background of AD susceptibility. PMID- 22045483 TI - Periodontal inflammation in relation to cognitive function in an older adult Danish population. AB - Inflammation plays a significant role in Alzheimer's disease (AD) pathogenesis. Studies have shown that systemic, peripheral infections affect AD patients. Cognitive dysfunction is a consistent finding in AD and periodontal disease is a chronic, peripheral infection often resulting in tooth loss. We hypothesized that older adults with periodontal inflammation (PI) or many missing teeth would show impaired cognition compared to subjects without PI or with few missing teeth, and among subjects with PI, those with many missing teeth would show impaired cognition compared to those with few missing teeth. The effect of PI/tooth loss on cognitive function [measured by Digit Symbol (DST) and Block Design (BDT) tests] was assessed in 70-year old Danish subjects. We found: 1) subjects with PI obtained lower mean DST scores compared to subjects without PI (p < 0.05); 2) subjects with many missing teeth had lower mean DST and BDT scores compared to subjects with few missing teeth (p < 0.05); 3) the association of PI with DST and BDT scores was dependant on the number of missing teeth (interaction: p = 0.03 and p = 0.06); and 4) education and previous cognitive scores (age 50) were important covariates. Subjects with PI had significantly lower adjusted mean DST scores compared to subjects without PI. However for adjusted BDT, the significance held only for subjects with few missing teeth. No difference in the adjusted DST and BDT scores was seen between subjects with many missing teeth compared to those with few missing teeth. These results support the hypothesis that PI may affect cognition. PMID- 22045484 TI - The BACE1-PSEN-AbetaPP regulatory axis has an ancient role in response to low oxygen/oxidative stress. AB - Oxygen homeostasis is essential for the development and normal physiology of an organism. Hypoxia causes the mitochondrial electron transport chain to generate higher levels of reactive oxygen species resulting in oxidative stress. Hypoxia can be a direct consequence of hypoperfusion, a common vascular component among Alzheimer's disease (AD) risk factors, and may play an important role in AD pathogenesis. Beta-site amyloid-beta A4 precursor protein-cleaving enzyme 1 (BACE1) is responsible, with gamma-secretase, for cleavage of the amyloid-beta protein precursor (AbetaPP) to produce amyloid-beta (Abeta) peptide. A recent study observed that oxidative stress increases BACE1 expression via a regulatory pathway dependent on gamma-secretase cleavage of AbetaPP and this increases Abeta peptide production. Zebrafish embryos represent normal cells in which complex and subtle manipulations of gene activity can be performed to facilitate analysis of genes involved in human disease. Here we identify and describe the expression of bace1, the zebrafish ortholog of human BACE1. We observe that the zebrafish AD related genes bace1, psen1, psen2, appa, and appb all show increased mRNA levels under hypoxia. A dominant negative form of psen1 putatively blocking gamma secretase activity blocks bace1 upregulation under hypoxia. Hypoxia increases catalase gene mRNA indicating increased oxidative stress but we did not observe increased levels of F2-isoprostanes that indicate peroxidation of arachidonic acid, possibly due to relatively low levels of arachidonic acid in zebrafish. Our results demonstrate that upregulation of PSEN1 & 2, AbetaPP and the gamma secretase-dependent upregulation of BACE1 is an ancient, conserved, and thus selectively advantageous response to hypoxia/oxidative stress. PMID- 22045485 TI - Interrelations between CSF soluble AbetaPPbeta, amyloid-beta 1-42, SORL1, and tau levels in Alzheimer's disease. AB - Recently, light has been shed on possible interrelations between the two most important pathological hallmarks of Alzheimer's disease (AD): the amyloid cascade and axonal degeneration. In this study, we investigated associations between sbetaAPPbeta, a product of the cleavage of the amyloid-beta protein precursor (AbetaPP) by beta-secretase, amyloid-beta 1-42 (Abeta42), soluble SORL1 (also called LR11 or SORLA), a receptor that is involved in AbetaPP processing, and the marker of axonal degeneration tau in the cerebrospinal fluid (CSF) of 76 patients with mild cognitive impairment (MCI), 61 patients with AD, and 17 patients with frontotemporal dementia, which neuropathologically is not related to the amyloid pathology. In the AD group, significant associations between sAbetaPPbeta, tau (p < 0.001), and soluble SORL1 (p < 0.001) were detected according to linear regression models. In patients with MCI, sAbetaPPbeta correlated significantly with tau (p < 0.001) and soluble SORL1 (p = 0.003). In the FTD group, only SORL1 (p = 0.011) was associated with sAbetaPPbeta and not tau. Abeta42 was found to be significantly related to tau levels in CSF in the MCI group (p < 0.001) and they tended to be associated in the AD group (p = 0.05). Our results provide further evidence for a link between the two facets of AD pathology, which is likely to be mediated by the binding of Abeta oligomers to specifically targeted neurons, resulting in stimulating tau hyperphosphorylation and neurodegeneration. PMID- 22045486 TI - Dietary supplementation with S-adenosyl methionine delayed amyloid-beta and tau pathology in 3xTg-AD mice. AB - S-adenosyl methionine (SAM) contributes to multiple pathways in neuronal homeostasis, several of which are compromised in age-related neurodegeneration and Alzheimer's disease. Dietary supplementation of transgenic mice with SAM maintained acetylcholine levels, cognitive performance, oxidative buffering capacity, and phosphatase activity, and reduced aggression, calcium influx, endogenous PS-1 expression, gamma-secretase activity, and levels of amyloid-beta (Abeta) and phospho-tau. Herein, we examined whether or not SAM could delay neuropathology in 3xTg-AD mice, which harbor mutant genes for human AbetaPP, PS-1 and tau. Mice received a standard AIN-76 diet with or without SAM (100 mg/kg diet) for 1 month commencing at 10 months of age or for 3 months commencing at 12.5 months of age; mice were sacrificed and examined for Abeta and tau neuropathology at 11 and 15.5 months of age, respectively. SAM supplementation reduced hippocampal intracellular AbetaPP/Abeta and phospho-tau immunoreactivity to a similar extent at both sampling intervals. Supplementation reduced the number of extracellular Abeta deposits by 80% (p < 0.01) at 11 months of age after 1 month of treatment but only by 24% (p < 0.34) at 15.5 months of age after 3 months of treatment. As anticipated, neurofibrillary tangles were not observed in mice at these young ages; however, supplementation reduced levels of phospho tau and caspase-cleaved tau within Sarkosyl-insoluble preparations in mice at 15.5 months of age. These limited analyses indicate that SAM can modulate the time course of AD neuropathology, and support further long-term analyses. PMID- 22045487 TI - The saturated fatty acid palmitate induces human monocytic cell toxicity toward neuronal cells: exploring a possible link between obesity-related metabolic impairments and neuroinflammation. AB - Obesity is linked to increased risk of Alzheimer's disease and cognitive impairment. Microglia-mediated neuroinflammation is implicated in neuronal loss. Elevated levels of fatty acids seen in obesity induce inflammation in peripheral tissues. Whether fatty acids promote neuroinflammation is unknown. Using an established neuroinflammation model involving human microglia-like THP-1 cells and SH-SY5Y neuroblastoma cells, we show that the saturated fatty acid palmitate, but not the unsaturated fatty acids oleate or linoleate, induces THP-1 cell pro inflammatory cytokine secretion and neurotoxicity. Inhibition of c-Jun NH2 terminal kinase (JNK) reduces this neurotoxicity. Therefore, elevated saturated fatty acids may induce neuroinflammation through pathways involving JNK activation. PMID- 22045488 TI - Amyloid-beta protein precursor gene expression in alzheimer's disease and other conditions. AB - Several lines of evidence suggest that AbetaPP gene expression could influence risk for Alzheimer's disease (AD). Using a highly sensitive multiplex fluorescent RT-PCR assay, we compared peripheral blood cells expression of AbetaPP mRNA among sporadic AD patients (n = 133), autosomal dominant early-onset AD cases (ADEOAD, n = 21), Down syndrome patients (n = 21), AD patients with AbetaPP duplication (n = 9), patients with recent ischemic stroke (n = 25), and healthy controls (n = 58). Compared to healthy controls (median = 0.98), AbetaPP expression was not increased in sporadic AD patients (median = 1.01, p = 0.42) nor in ADEOAD patients (median = 0.96, p = 0.26). Down syndrome patients as well as patients with AbetaPP duplication had significantly increased levels of AbetaPP mRNA compared to controls (median = 1.48 and median = 1.36, p < 0.0001 and p = 0.0007, respectively). A weaker but significant increase in relative amount of AbetaPP transcripts in patients who suffered from recent stroke was observed (median = 1.14, p = 0.0007). Our results do not support a pathogenic role of AbetaPP overexpression in sporadic AD although a small subset of patients displays AbetaPP overexpression in the same range as Down syndrome patients. PMID- 22045489 TI - Evidence of important, common disease processes contributing to late-life dementia that have not yet been recognized, characterized, or even named. PMID- 22045490 TI - Age-dependent and tissue-related glutathione redox status in a mouse model of Alzheimer's disease. AB - Glutathione plays an essential role in the intracellular antioxidant defense against oxidant radicals, especially the *OH radical. To understand the early and progressive cellular changes in the development of Alzheimer's disease (AD), we investigated reduced glutathione/oxidized glutathione (GSH/GSSG) status in a double mutated AD transgenic mouse model (B6.Cg-Tg), which carries Swedish amyloid-beta protein precursor mutation (AbetaPPswe) and exon 9 deletion of the PSEN1 gene. In this study, we quantified and compared both GSH/GSSG and mixed disulfide (Pr-SSG) levels in blood samples and three anatomic positions in brain (cerebrum, cerebellum, and hippocampus) at 3 age stages (1, 5, and 11 months) of AD transgenic (Tg)/wild type mice. The present study was designed to characterize and provide insight into the glutathione redox state of both brain tissues and blood samples at different disease stages of this Tg model. The level of Pr-SSG increased in all AD brain tissues and blood compared with controls regardless of age. The GSH/GSSG ratio in AD-Tg brain tissue started at a higher value at 1 month, fell at the transitional period of 5 months, right before the onset of amyloid plaques, followed by an increase in GSSG and associated decrease of GSH/GSSG at 11 months. These results suggest that formation of Pr-SSG may be an early event, preceding amyloid plaque appearance, and the data further implies that tissue thiol redox is tightly regulated. Notably, the high basal levels of mixed-disulfides in hippocampus suggest a potential for increased oxidative damage under oxidizing conditions and increased GSSG in this vulnerable region. PMID- 22045491 TI - Impact of less common and "disregarded" neurodegenerative pathologies on dementia burden in a population-based cohort. AB - Epidemiological studies investigating the pathological bases of late onset dementia focus on classical markers such as plaques and tangles. The significance of pathologies characteristically associated with rare dementia syndromes such as Pick bodies and severe neuronal loss are considered to be well defined. The significance of other pathologies, often accepted as a feature of neurodegenerative syndromes, such as Hirano bodies and gliosis is not clear. This study investigated the significance of these rarer and 'disregarded' pathologies to dementia in the population. A total of 627 individuals aged 71-103 from the Epidemiological CLInicoPathologial Studies in Europe (EClipSE) project with clinical dementia status at death determined were assessed. Pathologies assessed included Pick bodies, severe neuronal loss, gliosis, and granulovacuolar degeneration (GVD) in the cortex and/or hippocampus, along with brainstem plaques, tangles, neuronal loss, gliosis, pigmentary incontinence, and Lewy bodies. All pathologies were associated with dementia when controlling for plaques and tangles except Hirano bodies, GVD, and brainstem plaques. These included hippocampal and entorhinal gliosis; cortical, hippocampal, and entorhinal neuronal loss; along with brainstem neuronal loss, gliosis, pigmentary incontinence, Lewy bodies, and tangles. Pick bodies were present in five individuals, all with clinical dementia. These epidemiological data indicate that dementia in old age is associated with a broad range of pathological and anatomical substrates pointing to potential areas for future research, particularly the brainstem. PMID- 22045492 TI - Significance of lutein in red blood cells of Alzheimer's disease patients. AB - Red blood cells (RBC) of Alzheimer's disease (AD) patients are known to be in an excessively oxidized state (i.e., with a high accumulation of peroxidized phospholipids (PLOOH)). Previously we confirmed in vitro, in vivo murine, and in human studies that carotenoids can effectively inhibit accumulation of RBC PLOOH. Thus, the relationship between RBC carotenoids and PLOOH concentrations in AD patients is of interest. In this study, RBC carotenoids and PLOOH were evaluated in 28 normal control subjects (age: 74.1 +/- 1.3 years) and 28 patients with AD (age: 72.5 +/- 1.4 years). The concentrations of RBC carotenoids, especially lutein, in AD patients were significantly lower than in control subjects. An inverse relationship was seen between RBC carotenoids, especially lutein, and PLOOH concentrations in AD patients. These results suggest that RBC lutein, in particular, may contribute to suppression of PLOOH accumulation in RBC of AD patients. PMID- 22045493 TI - Environmental enrichment can prevent cognitive decline induced by dietary oxidative challenge. AB - Alzheimer's disease encompasses multiple risk factors; convergence may be necessary for clinical manifestation. Mice received a complete diet or one lacking folate and vitamin E and containing iron as a pro-oxidant, in a standard environment (SE) or a large cage containing objects to stimulate exploration/activity (enriched environment; EE). Mice declined in maze navigation on the deficient versus complete diet in the SE but not the EE. Mice on the complete diet demonstrated superior performance in the EE versus SE. The EE reduced brain lipid and protein oxidation. These findings suggest that maintaining nutrition and activity may delay age-related cognitive decline. PMID- 22045494 TI - c-Jun regulates the stability of anti-apoptotic DeltaNp63 in amyloid-beta-induced apoptosis. AB - p63, the structural and functional homologue of p53, is expressed either as a full-length isoform, containing a transactivation (TA) domain (TAp63), or as a truncated isoform, which lacks TA (DeltaNp63). Amyloid-beta (Abeta) incubation of neuronal cells results in stress-induced cell death through poorly understood mechanisms. We investigated the role of p63 in Abeta-induced stress. Our results show that Abeta-induced apoptosis of rat PC12 neuronal-like cells and primary cortical neurons was associated with stabilization of pro-apoptotic TAp63 and, most importantly, degradation of anti-apoptotic DeltaNp63 through a MAPK- and proteasome-dependent mechanism. This was associated with increased c-Jun, and partially modulated by tauroursodeoxycholic acid. As expected, classic genotoxic insults resulted in c-Jun upregulation and concomitant DeltaNp63 reduction. Endogenous and ectopic DeltaNp63 expression was also markedly reduced by c-Jun overexpression. Further, Abeta-mediated DeltaNp63 degradation occurred in a c-Jun dependent manner. Downregulation of c-Jun expression by specific c-Jun siRNA abrogated the reduction of DeltaNp63 levels following Abeta insult, whereas overexpression of c-Jun led to its degradation. c-Jun significantly decreased DeltaNp63 half-life. Together, these findings demonstrate that the abundance of anti-apoptotic DeltaNp63 in response to Abeta-induced cell stress is regulated by a c-Jun-dependent mechanism, and highlight the importance of finding novel targets for potential therapeutic intervention. PMID- 22045495 TI - Corticotrophin releasing factor accelerates neuropathology and cognitive decline in a mouse model of Alzheimer's disease. AB - Chronic stress has been suggested to influence the pathogenesis of Alzheimer's disease (AD); however, the mechanism underlying this influence remains unknown. In this study, we created a triple transgenic mouse model that overexpresses corticotrophin-releasing factor (CRF) and human amyloid-beta protein precursor (AbetaPP), to investigate whether increases in the expression of CRF can mimic the effects of stress on amyloid metabolism and the neurodegeneration. Tg2576 mice that overexpresses human AbetaPP gene were crossbreed with Tetop-CRF (CRF) mice and CaMKII-tTA (tTA) mice to create a novel triple transgenic mouse model that conditioned overexpresses CRF in forebrain and overexpresses human AbetaPP (called AbetaPP+/CRF+/tTA+, or TT mice). Then we evaluated serial neuro anatomical and behavioral phenotypes on TT mice using histological, biochemical, and behavioral assays. TT mice showed a Cushingoid-like phenotype starting at 3 months of age. At 6 months of age, these mice demonstrated increases in tissue soluble amyloid-beta (Abeta) and Abeta plaques in the cortex and hippocampus, as compared to control mice. Moreover, TT mice characterized substantial decreases in dendritic branching and dendritic spine density in pyramidal neurons in layer 4 of the frontal cortex and CA1 of the hippocampus. Finally, TT mice showed significantly impaired working memory and contextual memory, with a modest increase in anxiety-like behavior. Our results suggested genetic increases in the brain of CRF expression mimicked chronic stress on the effects of amyloid deposition, neurodegeneration, and behavioral deficits. The novel transgenic mouse model will provide a unique tool to further investigate the mechanisms between stress and AD. PMID- 22045496 TI - Monoamine oxidase-A physically interacts with presenilin-1(M146V) in the mouse cortex. AB - The concentration of presenilin-1 (PS-1) protein at the mitochondrial-associated aspect of the endoplasmic reticulum supports the potential for a mitochondrial influence of PS-1. Given that carriers of certain Alzheimer's disease (AD) related PS-1 variants are predisposed to clinical depression and that depression has been historically associated with the mitochondrial enzyme, monoamine oxidase A (MAO-A), we investigated cortical MAO-A function in the AD-related PS-1(M146V) knock-in mouse. The MAO-A system was clearly altered in the PS-1(M146V) mouse as revealed by (a) a mismatch between MAO-A protein expression and MAO-A activity; (b) changes in MAO-A-mediated monoaminergic neurotransmitter metabolism; (c) changes in non-cognitive behavior following treatment with the irreversible MAO-A inhibitor clorgyline; and (d) an increase in the potency of clorgyline in these same mice. We next investigated whether PS-1(M146V) could be influencing MAO-A directly. We observed (a) an enhanced MAO-A activity in necropsied PS-1(M146V) mouse cortical extracts incubated with DAPT (a PS-1 substrate-competitor); (b) the proximity of PS-1 with MAO-A and mitochondrial markers in cortical sections and in primary cortical neurons; (c) the co-segregation and co immunoprecipitation of PS-1 and MAO-A within the mitochondrial fraction; and (d) the co-immunoprecipitation of overexpressed PS-1(M146V) and MAO-A proteins from N2a lysates. The PS-1(DeltaEx9) and PS-1(D257A) variants, known to have low substrate-binding capacity, co-immunoprecipitated weakly with MAO-A. These combined data support a physical interaction between PS-1 and MAO-A that could influence MAO-A activity and contribute to the monoaminergic disruptions common to disorders as seemingly diverse as depression and AD. PMID- 22045497 TI - Identification of SPARC-like 1 protein as part of a biomarker panel for Alzheimer's disease in cerebrospinal fluid. AB - We have used proteomic fingerprinting to investigate diagnosis of Alzheimer's disease (AD). Samples of lumbar cerebrospinal fluid (CSF) from clinically diagnosed AD cases (n = 33), age-matched controls (n = 20), and mild cognitive impairment (MCI) patients (n = 10) were used to obtain proteomic profiles, followed by bioinformatic analysis that generated a set of potential biomarkers in CSF samples that could discriminate AD cases from controls. The identity of the biomarker ions was determined using mass spectroscopy. The panel of seven peptide biomarker ions was able to discriminate AD patients from controls with a median accuracy of 95% (sensitivity 85%, specificity 97%). When this model was applied to an independent blind dataset from MCI patients, the intensity of signals was intermediate between the control and AD patients implying that these markers could potentially predict patients with early neurodegenerative disease. The panel were identified, in order of predictive ability, as SPARC-like 1 protein, fibrinogen alpha chain precursor, amyloid-beta, apolipoprotein E precursor, serum albumin precursor, keratin type I cytoskeletal 9, and tetranectin. The 7 ion ANN model was further validated using an independent cohort of samples, where the model was able to classify AD cases from controls with median accuracy of 84.5% (sensitivity 93.3%, specificity 75.7%). Validation by immunoassay was performed on the top three identified markers using the discovery samples and an independent sample cohort which was from postmortem confirmed AD patients (n = 17). PMID- 22045498 TI - A phase I study of vinflunine in combination with capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and taxanes. AB - PURPOSE: A phase I study was performed to determine the maximal tolerated dose (MTD), recommended dose (RD), safety and efficacy of vinflunine when combined with capecitabine in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes, with pharmacokinetic blood sampling to test potential drug-drug interactions. PATIENTS AND METHODS: Sixteen patients with MBC who had received anthracyclines and taxanes in the neo/adjuvant setting, if progression occurred during or within 12 months of chemotherapy completion, and/or as first-line chemotherapy of MBC were enrolled. Vinflunine (VFL) was given on day 1 with capecitabine (CAPE) twice daily from days 1 to 14, every 3 weeks. Three dose levels (DL) were investigated (DL1: VFL 280 mg/m2 and CAPE 1,650 mg/m2/day, DL2: VFL 320 mg/m2 and CAPE 1,650 mg/m2/day and DL3: VFL 280 mg/m2 and CAPE 2,000 mg/m2/day). RESULTS: The RD was established as vinflunine 280 mg/m2 on day 1 plus capecitabine 1,650 mg/m2/day on days 1 to 14 given every 3 weeks. Dose-limiting toxicities were grade 4 neutropenia lasting at least 7 days for 2 patients, anorexia with fatigue for 1 patient and diarrhoea with fatigue, anorexia and febrile neutropenia for 1 patient. Neutropenia was the main toxicity of the combination, it was reported in 15 patients (93.8%) with grade 3 in 7 patients (43.8%) and 22.6% of cycles and grade 4 in 7 patients (43.8%) and 19.8% of cycles. Complications were rare with only one patient experiencing febrile neutropenia at DL exceeding the RD. The most frequent non-haematological toxicities were fatigue and gastrointestinal disorders; however, no grade 3 or 4 episode was observed at the RD. Hand-foot syndrome was reported in 5 patients (31.3%) and 22.6% of cycles, no episode of grade 3 was seen. Concerning pharmacokinetics, no modifications were detected for VFL, while slight accumulation between days 1 and 14 was observed for 5-FU formed from CAPE. The risk of clinical significant drug-drug interaction was considered weak. Objective partial responses were reported in 7 patients, yielding a response rate of 43.8% in the all-treated population according to the investigator assessment. CONCLUSIONS: The combination of vinflunine and capecitabine is safe and showed promising antitumour activity in MBC patients who have failed prior anthracyclines and taxanes. Further clinical development of this combination is warranted. PMID- 22045499 TI - Combination of frequency and amplitude-modulated model for the synthesis of normal and wheezing sounds. AB - Based on communication theory, this study proposes a model to synthesize normal and wheezing sounds. The model included five parts: the flow source as a transmitter, the frequency and amplitude-modulated (FM-AM) sounds, the accompanying noise as a modulator, the airway wall as a medium, and the microphone as a receiver. The hypothesis of modulation builds on that the deviation of frequency and amplitude of the sounds which cause from the deviation of collision speed of the air flow on the wall. The model was successful to simulate the normal breath and wheezing sounds. Furthermore, it provided a correct proof for the CORSA description, which indicates that the wheeze was contained in the domain frequency at 400 Hz, but a number of investigators have suggested that the range is actually between 80-1,600 Hz and 350-950 Hz by filter theory. This study modifies the signal source in Wodicka et al. model, and describes it in functional blocks. In fact, the design of the signal source base on the knowledge of the lung sound studies, especially the analysis of components in the frequency and time domains. We synthesized the required components to reproduce the lung sounds, and proposed a mechanism of wheeze which was examined by the computer simulation in the points of the system engineering view. PMID- 22045501 TI - Rapid progression of rhabdoid components of a composite high-grade glioma and rhabdoid tumor in the occipital lobe of an adult. AB - We report a very unusual case of a composite high-grade glioma and rhabdoid tumor in an adult. A 22-year-old woman presented with scintillating scotoma due to a solid tumor with surrounding brain edema in the right occipital lobe. The tumor was grossly resected. Histological examinations showed that the tumor was mainly composed of INI1-positive high-grade glioma tissue containing an INI1-negative rhabdoid component. She received radiation therapy and chemotherapy. Three months after the surgery, she again complained of visual disturbances, and tumor recurrence within the resection cavity was noted. A second operation was performed. The findings of histological examinations of the surgical specimen obtained during the second surgery were completely different from those of the specimen obtained during the initial surgery. Only the rhabdoid component showed remarkable proliferation and did not express INI1. Diffuse dissemination along the craniospinal axis eventually progressed, and she died 5 months after the initial diagnosis. We suggest that the inactivation of the INI1 gene affects potent proliferation activity and resistance to both chemotherapy and radiation therapy. PMID- 22045502 TI - Automated multiscale vessel analysis for the quantification of MR angiography of peripheral arteriogenesis. AB - PURPOSE: To automatically analyze the time course of collateralization in a rat hindlimb ischemia model based on signal intensity distribution (SID). MATERIALS AND METHODS: Time-of-flight magnetic resonance angiograms (TOF-MRA) were acquired in eight rats at 2, 7, and 21 days after unilateral femoral artery ligation. Analysis was performed on maximum intensity projections filtered with multiscale vessel enhancement filter. Differences in SID between ligated limb and a reference region were monitored over time and compared to manual collateral artery identification. RESULTS: The differences in SID correlated well with the number of collateral arteries found with manual quantification. The time courses of ultrasmall (diameter ?0.5 mm) and small (diameter ~0.5 mm) collateral artery development could be differentiated, revealing that maturation of the collaterals and enlargement of their feeding arteries occurred mainly after the first week postligation. CONCLUSION: SID analysis performed on axial maximum intensity projections is easy to implement, fast, and objective and provides more insight in the time course of arteriogenesis than manual identification. PMID- 22045503 TI - Characterization of the nonallelic homologous recombination hotspot PRS3 associated with type-3 NF1 deletions. AB - Nonallelic homologous recombination (NAHR) is the major mechanism underlying recurrent genomic rearrangements, including the large deletions at 17q11.2 that cause neurofibromatosis type 1 (NF1). Here, we identify a novel NAHR hotspot, responsible for type-3 NF1 deletions that span 1.0 Mb. Breakpoint clustering within this 1-kb hotspot, termed PRS3, was noted in 10 of 11 known type-3 NF1 deletions. PRS3 is located within the LRRC37B pseudogene of the NF1-REPb and NF1 REPc low-copy repeats. In contrast to other previously characterized NAHR hotspots, PRS3 has not developed on a preexisting allelic homologous recombination hotspot. Furthermore, the variation pattern of PRS3 and its flanking regions is unusual since only NF1-REPc (and not NF1-REPb) is characterized by a high single nucleotide polymorphism (SNP) frequency, suggestive of unidirectional sequence transfer via nonallelic homologous gene conversion (NAHGC). By contrast, the previously described intense NAHR hotspots within the CMT1A-REPs, and the PRS1 and PRS2 hotspots underlying type-1 NF1 deletions, experience frequent bidirectional sequence transfer. PRS3 within NF1 REPc was also found to be involved in NAHGC with the LRRC37B gene, the progenitor locus of the LRRC37B-P duplicons, as indicated by the presence of shared SNPs between these loci. PRS3 therefore represents a weak (and probably evolutionarily rather young) NAHR hotspot with unique properties. PMID- 22045504 TI - Agreement and reliability of pelvic floor measurements during contraction using three-dimensional pelvic floor ultrasound and virtual reality. AB - OBJECTIVES: Virtual reality is a novel method of visualizing ultrasound data with the perception of depth and offers possibilities for measuring non-planar structures. The levator ani hiatus has both convex and concave aspects. The aim of this study was to compare levator ani hiatus volume measurements obtained with conventional three-dimensional (3D) ultrasound and with a virtual reality measurement technique and to establish their reliability and agreement. METHODS: 100 symptomatic patients visiting a tertiary pelvic floor clinic with a normal intact levator ani muscle diagnosed on translabial ultrasound were selected. Datasets were analyzed using a rendered volume with a slice thickness of 1.5 cm at the level of minimal hiatal dimensions during contraction. The levator area (in cm(2)) was measured and multiplied by 1.5 to get the levator ani hiatus volume in conventional 3D ultrasound (in cm(3)). Levator ani hiatus volume measurements were then measured semi-automatically in virtual reality (cm(3) ) using a segmentation algorithm. An intra- and interobserver analysis of reliability and agreement was performed in 20 randomly chosen patients. RESULTS: The mean difference between levator ani hiatus volume measurements performed using conventional 3D ultrasound and virtual reality was 0.10 (95% CI, - 0.15 to 0.35) cm(3). The intraclass correlation coefficient (ICC) comparing conventional 3D ultrasound with virtual reality measurements was > 0.96. Intra- and interobserver ICCs for conventional 3D ultrasound measurements were > 0.94 and for virtual reality measurements were > 0.97, indicating good reliability for both. CONCLUSION: Levator ani hiatus volume measurements performed using virtual reality were reliable and the results were similar to those obtained with conventional 3D ultrasonography. PMID- 22045506 TI - SPINE X: improving protein secondary structure prediction by multistep learning coupled with prediction of solvent accessible surface area and backbone torsion angles. AB - Accurate prediction of protein secondary structure is essential for accurate sequence alignment, three-dimensional structure modeling, and function prediction. The accuracy of ab initio secondary structure prediction from sequence, however, has only increased from around 77 to 80% over the past decade. Here, we developed a multistep neural-network algorithm by coupling secondary structure prediction with prediction of solvent accessibility and backbone torsion angles in an iterative manner. Our method called SPINE X was applied to a dataset of 2640 proteins (25% sequence identity cutoff) previously built for the first version of SPINE and achieved a 82.0% accuracy based on 10-fold cross validation (Q(3)). Surpassing 81% accuracy by SPINE X is further confirmed by employing an independently built test dataset of 1833 protein chains, a recently built dataset of 1975 proteins and 117 CASP 9 targets (critical assessment of structure prediction techniques) with an accuracy of 81.3%, 82.3% and 81.8%, respectively. The prediction accuracy is further improved to 83.8% for the dataset of 2640 proteins if the DSSP assignment used above is replaced by a more consistent consensus secondary structure assignment method. Comparison to the popular PSIPRED and CASP-winning structure-prediction techniques is made. SPINE X predicts number of helices and sheets correctly for 21.0% of 1833 proteins, compared to 17.6% by PSIPRED. It further shows that SPINE X consistently makes more accurate prediction in helical residues (6%) without over prediction while PSIPRED makes more accurate prediction in coil residues (3-5%) and over predicts them by 7%. SPINE X Server and its training/test datasets are available at http://sparks.informatics.iupui.edu/ PMID- 22045507 TI - Effect of the spray application technique on the deposition of entomopathogenic nematodes in vegetables. AB - BACKGROUND: The present study compared entomopathogenic nematode delivery at the base of savoy cabbage and cauliflower, at the lower side of savoy cabbage and cauliflower leaves and in leek stems and the ground deposition using a five nozzle spray boom equipped with an ISO 08 flat fan, an air induction flat fan and Twinjet spray nozzles. Additionally, an air support system and a row application system were evaluated. RESULTS: Approximately 40% of the applied nematodes did not reach the foot of the cabbage plants. The use of an air support system or a row application system improved nematode deposition at the savoy cabbage base. Relative nematode deposition on the lower side of savoy cabbage leaves was 27.20%, while only 2.64% of the applied nematodes reached the lower side of cauliflower leaves. After spraying leek with a standard boom, a low relative nematode deposition (26.64%) was measured in the leek stem. Nozzle type affected the distribution of nematodes in droplet spots. CONCLUSION: Nozzle type has a minor effect on the number of entomopathogenic nematodes delivered on difficult to-reach targets. The use of modified spray application techniques directing the spray to the target site are necessary to increase the chances of contact of entomopathogenic nematodes with their target. PMID- 22045508 TI - The interplay of loneliness and depressive symptoms across adolescence: exploring the role of personality traits. AB - Based on current theories of depression, reciprocal links between loneliness and depressive symptoms are expected to occur. However, longitudinal studies on adolescent samples are scarce and have yielded conflicting results. The present five-wave longitudinal study from mid- to late adolescence (N=428, M age at T1=15.22 years; 47% female) examined the direction of effect between loneliness and depressive symptoms, using cross-lagged path analysis. In addition, the robustness of these prospective associations was tested by examining the role of the Big Five personality traits (i.e., extraversion, conscientiousness, agreeableness, neuroticism, and openness) as explaining factors and moderators. Results indicated that loneliness and depressive symptoms influenced one another reciprocally, and these reciprocal associations were not attributable to their mutual overlap with personality traits. In addition, neuroticism was found to be a moderator, in that the bidirectional effects between loneliness and depressive symptoms were only found in adolescents high in neuroticism. Practical implications are discussed, and suggestions for future research are outlined. PMID- 22045509 TI - Recurrent ovarian cancer: when and how to treat. AB - Notwithstanding continuing efforts to improve the primary treatment for ovarian cancer, most patients will ultimately develop recurrent disease. The benefits of detection and early systemic treatment of recurrence are now in doubt following the presentation of the MRC/EORTC CA125 surveillance trial. The impact of secondary cytoreductive surgery on survival requires more investigation. The role of antiangiogenic and other biological agents such as PARP inhibitors is becoming increasingly important for patients as an addition or alternative to the more conventional cytotoxic therapies available. Uncertainties and choices abound both in the treatment of recurrent ovarian cancer and the timing of such interventions. This article not only explores how to treat these patients but also the controversial issue of when to treat. Educating and involving the patient in decisions about their treatment options is of paramount importance. PMID- 22045510 TI - The role of sugars in dendritic cell trafficking. AB - Dendritic cells (DCs) are crucial components of the immune response, strategically positioned as immune sentinels. Complex trafficking and accurate positioning of DCs are indispensable for both immunity and tolerance. This is particularly evident for their therapeutic application where an unmet clinical need exists for DCs with improved migratory capacity upon adoptive transfer into patients. One critical step that directs the trafficking of DCs throughout the body is their egress from the vasculature, starting with their adhesive interactions with vascular endothelium under shear flow. Both tethering and rolling rely on interactions mediated by specific glycans attached to glycoproteins and glycolipids present on the DC surface. In DCs, surface glycosylation, including the expression of selectin ligands, changes significantly depending on the local microenvironment and the functional state of the cells. These changes have been documented and have potential implications in important cell functions such as migration. In this article, we review the glycobiological aspects in the context of DC interaction with endothelium, and offer insights on how it can be applied to modulate DC applicability in therapy. PMID- 22045512 TI - Synthesis and antimicrobial evaluation of some new cyclooctanones and cyclooctane based heterocycles. AB - The versatile synthon (E)-2-((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane-based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2 ((p-sulfonamidophenyl)methylene)cyclooctanone (5) showed excellent activity against Listeria monocytogenes. PMID- 22045511 TI - The nuts and bolts of low-level laser (light) therapy. AB - Soon after the discovery of lasers in the 1960s it was realized that laser therapy had the potential to improve wound healing and reduce pain, inflammation and swelling. In recent years the field sometimes known as photobiomodulation has broadened to include light-emitting diodes and other light sources, and the range of wavelengths used now includes many in the red and near infrared. The term "low level laser therapy" or LLLT has become widely recognized and implies the existence of the biphasic dose response or the Arndt-Schulz curve. This review will cover the mechanisms of action of LLLT at a cellular and at a tissular level and will summarize the various light sources and principles of dosimetry that are employed in clinical practice. The range of diseases, injuries, and conditions that can be benefited by LLLT will be summarized with an emphasis on those that have reported randomized controlled clinical trials. Serious life-threatening diseases such as stroke, heart attack, spinal cord injury, and traumatic brain injury may soon be amenable to LLLT therapy. PMID- 22045513 TI - Two-photon excited fluorescence lifetime measurements through a double-clad photonic crystal fiber for tissue micro-endoscopy. AB - This paper presents an endoscopic configuration for measurements of tissue autofluorescence using two-photon excitation and time-correlated single photon counting detection through a double-clad photonic crystal fiber (DC-PCF) without pre-chirping of laser pulses. The instrument performance was evaluated by measurements of fluorescent standard dyes, biological fluorophores (collagen and elastin), and tissue specimens (muscle, cartilage, tendon). Current results demonstrate the ability of this system to accurately retrieve the fluorescence decay profile and lifetime of these samples. This simple setup, which offers larger penetration depth than one-photon-based techniques, may be combined with morphology-yielding techniques such as photoacoustic and ultrasound imaging. PMID- 22045514 TI - Cytopathology of subacute thyroiditis. PMID- 22045515 TI - A systematic review of the effectiveness of occupational health and safety training. AB - OBJECTIVES: Training is regarded as an important component of occupational health and safety (OHS) programs. This paper primarily addresses whether OHS training has a beneficial effect on workers. The paper also examines whether higher engagement OHS training has a greater effect than lower engagement training. METHODS: Ten bibliographic databases were searched for pre-post randomized trial studies published in journals between 1996 and November 2007. Training interventions were included if they were delivered to workers and were concerned with primary prevention of occupational illness or injury. The methodological quality of each relevant study was assessed and data was extracted. The impacts of OHS training in each study were summarized by calculating the standardized mean differences. The strength of the evidence on training's effectiveness was assessed for (i) knowledge, (ii) attitudes and beliefs, (iIi) behaviors, and (iv) health using the US Centers for Disease Control and Prevention's Guide to Community Preventive Services, a qualitative evidence synthesis method. RESULTS: Twenty-two studies met the relevance criteria of the review. They involved a variety of study populations, occupational hazards, and types of training. Strong evidence was found for the effectiveness of training on worker OHS behaviors, but insufficient evidence was found of its effectiveness on health (ie, symptoms, injuries, illnesses). CONCLUSIONS: The review team recommends that workplaces continue to deliver OHS training to employees because training positively affects worker practices. However, large impacts of training on health cannot be expected, based on research evidence. PMID- 22045516 TI - In vivo assessment of neurodegeneration in Niemann-Pick type C mice by quantitative T2 mapping and diffusion tensor imaging. AB - PURPOSE: To quantitatively and noninvasively assess neurological disease progression in a mouse model of Niemann-Pick type C (NPC) disease by measuring white matter status with magnetic resonance imaging (MRI) techniques of T2 mapping and diffusion tensor imaging (DTI). MATERIALS AND METHODS: Quantitative T2 and DTI experiments were performed in vivo in NPC disease model and control mice at three timepoints to quantify differences and changes in white matter with measurements of T2 relaxation and DTI parameters. Histological staining for myelin content was also performed at two timepoints to compare with the MRI findings. RESULTS: The results of the T2 and DTI measurements show significant differences in white matter areas of the brain in the NPC disease model compared to control mice at several timepoints, and were seen to change over time in both groups. CONCLUSION: The findings of this study suggest that quantitative MRI measurements may be suitable in vivo biomarkers of disease status for future studies of NPC disease models. The changes in white matter measurements between timepoints in both control and NPC disease groups suggest that white matter structures continue to change and develop over time in the NPC model and can be tracked with MRI techniques. PMID- 22045517 TI - Factors associated with major infections in patients with granulomatosis with polyangiitis and systemic lupus erythematosus treated for deep organ involvement. AB - This study is an audit and a comparison of major infective complications in patients with granulomatosis with polyangiitis (GPA) and systemic lupus erythematosis (SLE). Data were collected on consecutive patients attending a single treatment approach, multidisciplinary vasculitis centre who met diagnostic criteria for GPA and SLE from 01/01/2006 to 30/06/2006. Immunosuppressive treatment is used in this clinic with guidelines targeting avoidance of neutropenia. For each patient, documentation was made of disease presentation, organ involvement and therapy used. A history of major infections requiring hospital admission and intravenous antimicrobials pre- and post-diagnosis was recorded. Patients with GPA received a higher cumulative dose of cyclophosphamide, had a higher median age, shorter period of follow-up and had lower mean and nadir absolute lymphocyte counts and nadir neutrophil counts. GPA patients had more major infections per patient years (P = 0.0027) and respiratory tract infections (P = 0.0031) per patient years. Relative risk (RR) of major infection was significantly increased with methylprednisolone, RR 11.1 (P = <0.0001), cyclophosphamide, RR 2.0 (P = 0.0246) and the intensive phase of treatment, RR 13.3 (P = <0.0001). Marked lymphopenia was common in both groups during follow-up and was associated with an increased risk of major infection (P = 0.0020). Major infections, in particular respiratory tract infections, are more common in those treated for GPA than SLE. This may be due to a combination of factors including greater doses and duration of methyprednisolone and cyclophosphamide. We recommend treatment strategies that aim not only to avoid neutropenia but that also identify lymphopenia as a risk factor for major infection. PMID- 22045518 TI - Hypovitaminosis D and response to cholecalciferol supplementation in patients with autoimmune and non-autoimmune rheumatic diseases. AB - Recent reports suggest a role of hypovitaminosis D in the pathogenesis of inflammatory autoimmune diseases (ARD); we investigated 25(OH)vitamin D plasma level before and after supplementation in ARD and NARD (non-ARD: osteoporosis and/or OA) patients. We retrospectively evaluated 572 consecutive clinical records of adult patients at immuno-rheumatology and rehabilitative units of our institution from January 2006 to October 2009. We excluded patients with vitamin D supplementation or renal failure, primary hyperparathyroidism, liver failure. We recorded 25(OH)vitamin D plasma concentration of 245 patients together with other clinical data. We then evaluated 25(OH)vitamin D plasma concentration of 100 (43 ARD and 57 NARD) patients previously included who underwent 750-1,000 UI/die 25(OH)vitamin D supplementation for at least 6 months. Appropriate statistical analysis was performed. The median 25(OH)vitamin D concentration was not significantly different between 119 ARD [33.4 (IQR 22.5-54.9) nmol/l] and 126 NARD patients 32.9 (IQR 18.7-50.2). In stepwise logistic regression, female sex (F:13.7), winter-spring season (F:5.6) and older age (F:5.3), but not ARD, predicted plasma 25(OH)vitamin D <75 nmol/l. Cholecalciferol supplementation increased 25(OH)vitamin D plasma concentration equally in both ARD and NARD; however, only 29/100 patients reached a plasma level >=75 nmol/l without differences between ARD and NARD (chi(2) = n.s.). Hypovitaminosis D is common in rheumatic patients. Sex and age but not ARD are risk factors for this condition. 750-1,000 UI/die of cholecalciferol is not sufficient to normalize plasma level in these patients. Increase of plasma 25(OH)vitamin D after treatment is not influenced by the presence of an inflammatory autoimmune disease. PMID- 22045520 TI - Complexation and conjugation approaches to evaluate siRNA delivery using cationic, hydrophobic and amphiphilic peptides. AB - In this study, we used solid phase synthesis to prepare three kinds of peptides and then formulated their peptide-siRNA complexes and peptide-siRNA conjugates. Both the complexation and conjugation systems were nontoxic and allowed the delivery of siRNA into the cytoplasm without the need for any transfection agents and with subsequent inhibition of gene expression. PMID- 22045519 TI - The effect of vascular endothelial growth factor on aggrecan and type II collagen expression in rat articular chondrocytes. AB - The expression of vascular endothelial growth factor (VEGF) directly correlates with the Mankin score and the degree of cartilage destruction. The biological activity of VEGF on articular cartilage remains unknown, so this study was performed to investigate the effect of VEGF on aggrecan and type II collagen expression in vitro. We carried out this study at the Center Laboratory of Renmin Hospital at Wuhan University. Rat articular chondrocytes were cultured in a monolayer. Then, the experiment was divided into 4 groups: group A (control group), without any disposal; group B, treated with 10 ng/ml VEGF; group C, treated with 10 ng/ml IL-1beta; and group D, treated with 10 ng/ml VEGF + 10 ng/ml IL-1beta. After 48 h, messenger RNA (mRNA) expression of aggrecan and type II collagen was evaluated by real-time polymerase chain reaction (real-Time PCR), and protein expression of aggrecan and type II collagen was detected by Western blotting. VEGF was found to significantly inhibit the expression of aggrecan and type II collagen at the gene and protein levels. These findings suggest that VEGF may result in degeneration of articular cartilage by inhibiting the synthesis and expression of aggrecan and type II collagen. PMID- 22045521 TI - [Biologics - nomenclature and classification]. AB - Biological medicines are a heterogeneous group of drugs that are produced by living organisms using genetic or biological technology. Unlike chemically derived small molecules biologics are structurally complex making characterization and manufacturing difficult. Moreover, biological medicines show a great variety concerning their clinical use. To appropriately consider these particularities, there are other standards and guidelines for approval of similar derivatives of biologics, the so-called biosimilars or follow-on biologics. In contrast to a generic medicinal product containing a chemically identical active ingredient, a biosimilar is only expected to be similar to the innovator drug. Nowadays, monoclonal antibodies, fragments of antibodies, and fusion proteins manufactured by recombinant procedures play an important role. They have been used in many specialties for diagnostic and therapeutic purposes and are subject to continuous further development and improvement. Their nomenclature is based on a classification by the WHO which allows drawing conclusions for class of substance, origin, and pharmacological target. PMID- 22045522 TI - [Proteins in rheumatology and clinical immunology]. AB - Twelve years ago the tumour necrosis factor (TNF) inhibitors revolutionised the therapy of rheumatoid arthritis and other inflammatory rheumatic diseases. Today, in addition to anti-cytokine strategies, immunosuppressive biologicals have been developed that delete B-lymphocytes or inhibit the activation of T-lymphocytes. The spectrum of indications for these protein drugs will broaden substantially in the near future and will likely include also diseases with orphan status (incidence below 1:10'000). Used in the right indication and with knowledge of molecular effects as well as clinical adverse effects these new drugs do not appear to be more dangerous than conventional disease modifying agents (DMARDs). PMID- 22045523 TI - [Proteins in haematology]. AB - The introduction of monoclonal antibodies has been a milestone in the treatment of hematologic neoplasms. The CD20 antibody rituximab has been a trailblazer and represents meanwhile a fixed combination partner of different first- and second line chemotherapies in CD20-positive B-cell-non-Hodgkin's lymphoma (NHL). Rituximab maintenance is established in follicular lymphoma. The drug is also used for the treatment of non-malignant hematologic diseases (i.e. immunthrombocytopenia). Rituximab was followed by the CD52 antibody alemtuzumab and recently by the CD20 antibody ofatumumab for the therapy of CLL and the radioimmunconjugate ibritumomab-tiuxetan indicated for the treatment of refractory or relapsed CD20-positive follicular lymphoma or as consolidation after induction chemotherapy. In the near future, approval of several new antibodies is expected. For the treatment of refractory or relapsed Hodgkin's lymphoma and relapsed systemic anaplastic large cell lymphoma, the CD30 antibody brentuximab vedotin has been shown to be a highly active new treatment option. PMID- 22045524 TI - [Recombinant proteins as therapeutic compounds in clinical oncology]. AB - The in vitro production of recombinant protein molecules has fostered a tremendous interest in their clinical application for treatment and support of cancer patients. Therapeutic proteins include monoclonal antibodies, interferons, and haematopoietic growth factors. Clinically established monoclonal antibodies include rituximab (targeting CD20-positive B-cell lymphomas), trastuzumab (active in HER-2 breast and gastric cancer), and bevacizumab (blocking tumor-induced angiogenesis through blockade of vascular-endothelial growth factor and its receptor). Interferons have lost much of their initial appeal, since equally or more effective treatments with more pleasant side effects have become available, for example in chronic myelogenous leukaemia or hairy cell leukaemia. The value of recombinant growth factors, notably granulocyte colony stimulating factor (G CSF) and erythropoietin is rather in the field of supportive care than in targeted anti-cancer therapy. Adequately powered clinical phase III trials are essential to estimate the true therapeutic impact of these expensive compounds, with appropriate selection of clinically relevant endpoints and sufficient follow up. Monoclonal antibodies, interferons, and growth factors must also, and increasingly so, be subjected to close scrutiny by appropriate cost-effectiveness analyses to ensure that their use results in good value for money. With these caveats and under the condition of their judicious clinical use, recombinant proteins have greatly enriched the therapeutic armamentarium in clinical oncology, and their importance is likely to grow even further. PMID- 22045525 TI - [Proteins influencing the blood coagulation]. AB - This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech. PMID- 22045526 TI - [Proteins support stem cells - use of protein therapeutics in hematopoietic stem cell transplantation]. AB - Hematopoietic stem cell transplantation (HSCT) has evolved from a largely experimental therapeutic approach three decades ago to a well-established therapy today for many malignant and non-malignant disorders of the hematopoietic and the immune system. Although it is per se a therapy by transmission of cells, protein therapeutics such as growth factors and antibodies are relevant in all phases of a HSCT and substantially contribute to the success of this often only curative treatment. This review discusses HSCT with a particular focus on the protein therapeutics involved. Granulocyte colony stimulating factor (G-CSF) for mobilization of stem cells to the peripheral blood, the polyclonal anti-T-cell globulin (ATG) and the monoclonal antibodies alemtuzumab and etanercept for prophylaxis and therapy of graft versus host disease (GvHD) are highlighted. Also rituximab, palivizumab and polyclonal intravenous immunoglobulins for treating infections in post-transplant patients are discussed. Since our understanding of cell surface receptors, cytokine and signaling pathways is increasing, there will emerge new targets for directed therapy by proteins in the future. They may have the potential to further improve the success and to widen theapplication of HSCT. PMID- 22045527 TI - [Erythropoiesis stimulating agents]. AB - Since the 90's, human erythropoietin is produced recombinantly and used clinically. There are various products from different suppliers, which differ primarily in their production but not in their half-life or effectiveness. 2001 genetically modified darbepoetin alpha was launched, which is characterized by an approximately three times longer half-life. A further extension of the half-life to 130 hours is achieved with the current continuous erythropoietin receptor activator (CERA), which therefore must be applied only once or twice a month. The indication for epoetin therapy is primarily for the symptomatic renal anemia and chemotherapy-associated anemia. Corrections of low hemoglobin levels in asymptomatic patients are not allowed. The generally recommended hemoglobin target range is 10-12 g/dl. Hb values > 13 g/dl should be avoided because they are associated with significant adverse effects and do not improve patient survival. PMID- 22045529 TI - [Biosimilars]. AB - Biosimilars are biological medicinal products referring to an existing biological originator product and submitted to regulatory authorities formarketing authorization by an independent applicant after the patent has expired. The European Medicines Agency (EMA) has issued overarching and specific guidelines that should be fulfilled in order to receive approval as biosimilar. In accordance with these guidelines biosimilars of recombinant somatropin, epoetin alfa, and granulocyte-colony stimulating factor have gained market authorisation in the EU. Similarity in terms of quality, safety and efficacy to a reference product was demonstrated. Points to consider when switching from the innovator product to a biosimilar, or from one biosimilar to another, are reported. INN naming, labelling, pharmacovigilance issues, interchangeability, and substitution of biosimilars are still a matter of discussion. PMID- 22045530 TI - Performing artists, part 1. PMID- 22045528 TI - [Immunostimulating drugs and cytokines]. AB - Cytokines are essential regulators of hematopoesis and the immune system. Genetic engineering of recombinant cytokines has facilitated their implementation in many clinical areas. In the field of oncology the granulopoetic human growth factors G CSF and GM-CSF are of particular importance. They can be applied to prevent chemotherapy induced neutropenia. Furthermore, they allow for mobilization of hematopoetic stem cells in order to obtain peripheral blood stem cell transplants. Another class of cytokines, the interferons, possess immunomodulating, antiproliferative, and antiviral properties. While the significance of interferon alfa as an antitumor agent is dwindling, it still plays a very important role in the therapy of chronic hepatitis b and c. Interferon beta is successfully used to treat multiple sclerosis. Among the heterogenous group of interleukines in particular interleukin 2 has reached clinical practice as an immunostimulating agent in the therapy of metastatic renal cell carcinoma. Many other cytokines have yet to undergo clinical trials. PMID- 22045531 TI - Incidence of injury and attitudes to injury management in skilled flute players. AB - OBJECTIVE: The flute is a highly popular instrument, yet little is known about the potential injury association with playing this instrument. PARTICIPANTS: Twenty flautists from a major music training institution volunteered to participate in this project, and had played the flute for a minimum of ten years. METHODS: A specifically designed musicians' health questionnaire was used to determine injury rates in a group of skilled collegiate flute players majoring in music to examine self-reported perceptions of performance-related musculoskeletal disorder causation and approaches to managing these conditions. RESULTS: All except one player reported suffering from a performance-related musculoskeletal disorder, with pain present for longer than 3 months in two thirds of this group. The most common approach by the flautists was to take Alexander lessons rather than seeking health professional advice. Most attributed their symptoms to long hours of practice, poor posture and the presence of performance anxiety. CONCLUSIONS: Flautists in this sample reported high rates of performance-related musculoskeletal disorders with the majority having been present for longer than 3 months. The approach to management often did not involve consultation with a health professional qualified to diagnose musculoskeletal conditions. PMID- 22045532 TI - Development and implementation of an in-house healthcare program for university level performing artists. AB - OBJECTIVES: Performing Arts Medicine (PAM) specializes in providing healthcare to performing artists. Participation in the performing arts can cause injury and impair performing artists' art and livelihood. While healthcare is often available for professionals, university-level students remain underserved. Therefore, our objective was to describe the successful development and implementation of the George Mason University university-level PAM program as a possible template for other institutions. PARTICIPANTS: Collaborations among the Athletic Training Education Program, the Department of Dance, and the University Central Administration. METHODS: An athletic trainer provided free healthcare services that included preventive care, acute emergency and non-emergency injury care, assessment and referral, and rehabilitation to the students. RESULTS: Nearly 100 different injuries and 300 assessment and treatment healthcare sessions were provided in the first year of the program. Program benefits included improved healthcare for dancers, increased learning opportunities for students, research opportunities, and enhanced university recognition. CONCLUSIONS: The PAM program offers primary injury prevention by implementing performing artists specific interventions and secondary prevention to improve their health outcomes. Overall, we hope the program's success encourages other institutions to provide in-house healthcare to their students, eventually helping improve healthcare status of all university-level performing artists. PMID- 22045533 TI - The lived experience of working as a musician with an injury. AB - OBJECTIVE: Research and clinical experience have shown that musicians are at risk of acquiring playing-related injuries. This paper explores findings from a qualitative research study examining the lived experience of professional instrumental musicians with playing-related injuries, which has thus far been missing from the performing arts health literature. METHODOLOGY: This study employed a phenomenological methodology influenced by van Manen to examine the lived experiences of professional musicians with playing-related injuries. PARTICIPANTS AND METHODS: Ten professional musicians in Ontario, Canada were interviewed about their experiences as musicians with playing-related injuries. Six of the participants later attended a focus group where preliminary findings were presented. RESULTS: The findings demonstrate a need for education about risk and prevention of injuries that could be satisfied by healthcare professionals and music educators. CONCLUSIONS: The practice and training of healthcare professionals should include the "tactful" (van Manen) delivery of care for this important and vulnerable population. PMID- 22045534 TI - Inter-rater reliability of a musculoskeletal screen as administered to female professional contemporary dancers. AB - OBJECTIVE: The purpose of this study is to determine the inter-rater reliability of commonly used musculoskeletal screening components in a population of contemporary professional dancers. PARTICIPANTS: Study participants were 30 women from six contemporary dance companies between the ages of 18 and 32, with a mean age of 24, and Body Mass Index of 22.4. METHODS: 101 items were assessed in the categories of Static Posture, the Beighton 9-Point Hypermobility Test, Flexibility, Strength, and Dynamic Posture, based upon the Pilot 2006 Dance USA Annual Post-Hire Health Screen for Professional Dancers. Testing was non-ordered, using 2 of the 4 available testers, with variable assignment of the lead tester. RESULTS: High percent agreement was found for the subcategories of hallux valgus, pelvic tilt, and forefoot alignment, flexor hallucis, iliopsoas, hip internal rotation flexed, external rotation extended, and soleus extensibility, composite Beighton, and for most measures within the dynamic posture category. Low to moderate percent agreement was found in the strength tests. CONCLUSION: Although this study demonstrated moderate to high percent agreement between raters, further test refinement is needed to improve the reliability of the measurement components. PMID- 22045535 TI - Incorporating flow into practice and performance. AB - In the music profession, individuals often work under stress filled conditions. This is especially true for individuals making their living as performing musicians. Musical performance anxiety has been well documented in both students and professionals. For some, the experience may lead to a termination of what might otherwise remain a successful performing career. Humans are susceptible to anxiety and so the phenomenon of musical performance anxiety is not likely to disappear. Learning how to effectively deal with musical performance anxiety is paramount for those in the performing arts. Entering a state of flow, in which there is total absorption in an activity, allows for the possiblity of any ensuing anxiety to become facilitative, rather than debilitative. This article will discuss several characteristics of flow, as defined by Mihalyi Csikszentmihalyi, and provide practical applications for musical practice and performance in an attempt to counterbalance musical performance anxiety. Musicians will benefit from a closer examination of the elements of flow and means of incorporating these elements into practice and performance. PMID- 22045536 TI - Big Five personality traits and performance anxiety in relation to marching arts satisfaction. AB - OBJECTIVE: To examine the Big Five personality traits and performance anxiety in relation to marching arts satisfaction. PARTICIPANTS: Data were collected from 278 instrumentalists (i.e., brass players and percussionists) and color guard performers (e.g., dancers) representing six world class drum and bugle corps. METHOD: PARTICIPANTS completed three measures: the Adolescent Personal Style Inventory was used to measure the Big Five personality factors: Agreeableness, Conscientiousness, Emotional Stability, Extraversion, and Openness; the Performance Anxiety Questionnaire - used to assess somatic and cognitive symptoms of performance anxiety; and the Marching Arts Satisfaction - used to assess for the physical, social, and contextual environments of drum and bugle corps. RESULTS: Correlation and multiple regression analyses revealed concurrent relationships between the Big Five and performance anxiety with satisfaction. A linear combination of the Big Five traits and Performance Anxiety accounted for 36% of the total variance in satisfaction, with Extraversion, Emotional Stability, and Performance Anxiety contributing significant unique variance. CONCLUSIONS: The findings of the present study suggest that performers who are extraverted, conscientious, and effective at managing general stress - and performance stress in particular - find a greater sense of satisfaction with their participation in world class drum and bugle corps. PMID- 22045537 TI - Physical and environmental factors contributing to music related injuries among children. AB - OBJECTIVE: This study asserts that a combination of environmental and physical factors influence the child pianist's risk for developing a music related injury. PARTICIPANTS: 26 participants (10 piano students, 10 parents, and 6 piano teachers) were included in this study. Piano students were ages 5 to 11 and currently enrolled in piano lessons. METHODS: Three questionnaires addressed the factors affecting the participant groups (children, parents, and piano teachers). Participants completed one questionnaire about the factors contributing to the development of music related injuries in child pianists. Descriptive statistics were used to analyze the results. RESULTS: None of the student participants had pain, discomfort, or a history of music related injuries. The majority of parents and teachers reported that the lighting was the most important environmental factor affecting students' playing in the piano lesson. 70% of parents reported that the presence of family members most greatly affected students' practicing at home. 100% of the teachers and parents reported that the most important physical factors contributing to students' injury-free playing were playing with proper technique and learning effective practice strategies. All parents and students who were taking piano lessons in their homes reported the most satisfaction with their piano lesson environment. CONCLUSION: The results of this study do not support a relationship between environmental or physical factors and the presence of pain, discomfort, or music related injuries in students. PMID- 22045538 TI - Postural problems of the left shoulder in an orchestral trombonist. AB - Professional musicians require a disciplined and balanced regime of practise and performance to enable them to cope with the physical challenges of their chosen instrument and to reduce the risk of work- related injury. If practise or performance strategies are suddenly changed, permanent damage may occur even in a player with a mature, well-established technique. The trombone presents unique physical challenges which are heightened by recent developments in instrumental design as well as by orchestral working conditions. This study presents the experiences of a professional orchestral trombonist who worked as a principal player in a UK orchestra until his performing career was cut short by a performance related injury. His personal approach to practise is discussed in the context of the physical and professional challenges associated with contemporary orchestral practices. The case study demonstrates the importance of considering the interplay between psychological and physical factors in the development and treatment of injury in musicians. PMID- 22045539 TI - Is hypermobility syndrome (HMS) a contributing factor for chronic unspecific wrist pain in a musician? If so, how is it evaluated and managed? AB - OBJECTIVES: The musician complaining of chronic pain commonly presents with subtle and complicated findings. Joint hypermobility is common in these individuals. The diagnosis of joint hypermobility syndrome (HMS) does not merely involve joint laxity, but connective tissue impairment throughout the body as well as perhaps involving the neurological system. As the aging process gradually reduces joint laxity, chronic pain and various impairments may linger. This report investigates HMS as it relates to a case study involving a musician suffering with chronic joint pain and HMS. METHODS: Literature review and case description. RESULTS: HMS involves more than just joint laxity and may be the cause of various chronic pain dysfunctions. The prognosis for recovery from HMS is poor, but the education and psychological aspect is extremely beneficial to the patient's health and well-being. CONCLUSIONS: This case report identified a musician with CUWP and HMS. Joint hypermobility syndrome does not merely involve joint laxity, but involves connective tissue impairment throughout the body as well as perhaps involving the body's neurological system. Joint hypermobility is common in musicians. PMID- 22045540 TI - Narrative reflections on occupational transitions. PMID- 22045541 TI - Knowledge transfer in work practice: challenging the status quo to meet the needs of end users. PMID- 22045542 TI - Direct determination of gold in rock samples using collision cell quadrupole ICP MS. AB - This study investigated the determination of Au in rock samples using collision cell quadrupole inductively coupled plasma mass spectrometry (ICP-MS). It is essential to remove various interferents using a collision cell because polyatomic ions such as (181)Ta(16)O(+) and (180)Hf(16)O(1)H(+) can interfere with the direct determination of monoisotopic (197)Au when using ICP-MS. The addition of oxygen as a reaction gas removed isobaric interferents by transforming TaO(+) and HfOH(+) to TaO(2)(+), TaO(3)(+), and HfO(2)H(+), HfO(3)H(+), respectively, in the cell without significant Au(+) loss. The ion kinetic energy effect (IKEE) due to the potential difference between the plasma and the hexapole affected the reactions in the cell. Au and interfering ions were very sensitive to cell bias voltage (Vc) at constant plasma potential (Vp) and quadrupole bias voltage (Vq). Under the condition of hot plasma, the transmission of ions was promoted, and the maximum Au signal intensity was 50% greater than under normal conditions. At Vc > 7 V, TaO(+) ions were removed to background level. Optimized conditions for real sample analysis were obtained by introducing He as an additional collision gas in hot plasma. TaO(+) ions were removed to background level at He flow rates above 0.6 mL min(-1), and the Au signal remained high. The detection limit (three times the standard deviation of the blank) of this method was 3.06 pg g(-1). The results for reference materials (STM 1 and DGPM-1) and spiked samples showed good agreement between specified and measured concentrations. PMID- 22045543 TI - Influence of amino acid composition and phosphorylation on the ion yields of peptides in MALDI-MS. AB - The influence of arginine (Arg), lysine (Lys), and phenylalanine (Phe) residues and phosphorylation on the molecular ion yields of model peptides have been quantitatively studied using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry in both positive- and negative-ion mode. The results obtained from these experiments have been interpreted from the standpoint of two different components, namely, desorption and ionization, on the basis of the physicochemical properties of constituent amino acids of the model peptides. The presence of basic residues such as Arg and Lys enhanced the ion yields of protonated molecules [M + H](+). An N-terminal rather than a C-terminal Arg residue was advantageous for the formation of both [M + H](+) and [M - H](-). The presence of the Phe residue resulted in the increase of the ion yields of both [M + H](+) and [M - H](-). In contrast, the presence of phosphate group(s) contributed to the suppression of the yields of both [M + H](+) and [M - H](-) due to the loss of phosphate group. The detection limits for both [M + H](+) and [M - H](-) of model peptides have been evaluated. PMID- 22045544 TI - Sensitivity "hot spots" in the direct analysis in real time mass spectrometry of nerve agent simulants. AB - Presented here are findings describing the spatial-dependence of sensitivity and ion suppression effects observed with direct analysis in real time (DART). Continuous liquid infusion of dimethyl methyl phosphonate (DMMP) revealed that ion yield "hot spots" did not always correspond with the highest temperature regions within the ionization space. For instance, at lower concentrations (50 and 100 MUM), the highest sensitivities were in the middle of the ionization region at 200 degrees C where there was a shorter ion transport distance, and the heat available to thermally desorb neutrals was moderate. Conversely, at higher DMMP concentrations (500 MUM), the highest ion yield was directly in front of the DART source at 200 degrees C where it was exposed to the highest temperature for thermal desorption. In matching experiments, differential analyte volatility was observed to play a smaller role in relative ion suppression than differences in proton affinity and the relative sampling positions of analytes. At equimolar concentrations sampled at the same position, suppression was as high as 26* between isoquinoline (proton affinity 952 kJ mol(-1), boiling point 242 degrees C) and p-anisidine (proton affinity 900 kJ mol(-1), boiling point 243 degrees C). This effect was exacerbated when sampling positions of the two analytes differed, reaching levels of relative suppression as high as 4543.0* +/- 1406.0. To mitigate this level of relative ion suppression, sampling positions and molar ratios of the analytes were modified to create conditions in which ion suppression was negligible. PMID- 22045545 TI - The psychophysics of uneconomical choice: non-linear reward evaluation by a nectar feeder. AB - Uneconomical choices by humans or animals that evaluate reward options challenge the expectation that decision-makers always maximize the return currency. One possible explanation for such deviations from optimality is that the ability to sense differences in physical value between available alternatives is constrained by the sensory and cognitive processes for encoding profitability. In this study, we investigated the capacity of a nectarivorous bat species (Glossophaga commissarisi) to discriminate between sugar solutions with different concentrations. We conducted a two-alternative free-choice experiment on a population of wild electronically tagged bats foraging at an array of computer automated artificial flowers that recorded individual choices. We used a Bayesian approach to fit individual psychometric functions, relating the strength of preferring the higher concentration option to the intensity of the presented stimulus. Psychometric analysis revealed that discrimination ability increases non-linearly with respect to intensity. We combined this result with a previous psychometric analysis of volume perception. Our theoretical analysis of choice for rewards that vary in two quality dimensions revealed regions of parameter combinations where uneconomic choice is expected. Discrimination ability may be constrained by non-linear perceptual and cognitive encoding processes that result in uneconomical choice. PMID- 22045546 TI - Gestational age at cervical length measurement and preterm birth in twins. AB - OBJECTIVES: To estimate the risk of preterm delivery of twin pregnancies based upon sonographic cervical length measurement and gestational age at measurement. METHODS: Twin pregnancies that delivered between 1999 and 2005 and that underwent sonographic measurement of cervical length between 13 and 34 + 6 weeks' gestation were identified and a retrospective review performed. Women with anomalous pregnancies, multifetal reduction, cerclage placement or medically indicated deliveries before 35 weeks were excluded. Logistic regression analysis was used to estimate the risk of preterm delivery before 35 weeks. RESULTS: A total of 561 women underwent 2975 sonographic cervical length measurements during the study period. The rate of preterm delivery before 35 weeks was 19.4%. The risk of delivery before 35 weeks decreased by approximately 5% for each additional mm of cervical length (odds ratio (OR) 0.95 (95% CI, 0.93-0.97); P < 0.001) and by approximately 6% for each additional week at which the cervical length was measured (OR 0.94 (95% CI, 0.92-0.96); P < 0.001). CONCLUSION: The gestational age at which cervical length is measured is an important consideration when estimating the risk of spontaneous preterm birth in twins. The risk of preterm delivery is increased at earlier gestational ages and as cervical length decreases. PMID- 22045547 TI - The structure-activity relationship in herbicidal monosubstituted sulfonylureas. AB - BACKGROUND: The herbicide sulfonylurea (SU) belongs to one of the most important class of herbicides worldwide. It is well known for its ecofriendly, extreme low toxicity towards mammals and ultralow dosage application. The original inventor, G Levitt, set out structure-activity relationship (SAR) guidelines for SU structural design to attain superhigh bioactivity. A new approach to SU molecular design has been developed. RESULTS: After the analysis of scores of SU products by X-ray diffraction methodology and after greenhouse herbicidal screening of 900 novel SU structures synthesised in the authors' laboratory, it was found that several SU structures containing a monosubstituted pyrimidine moiety retain excellent herbicidal characteristics, which has led to partial revision of the Levitt guidelines. CONCLUSIONS: Among the novel SU molecules, monosulfuron and monosulfuron-ester have been developed into two new herbicides that have been officially approved for field application and applied in millet and wheat fields in China. A systematic structural study of the new substrate-target complex and the relative mode of action in comparison with conventional SU has been carried out. A new mode of action has been postulated. PMID- 22045548 TI - An effective method for accurate prediction of the first hyperpolarizability of alkalides. AB - The proper theoretical calculation method for nonlinear optical (NLO) properties is a key factor to design the excellent NLO materials. Yet it is a difficult task to obatin the accurate NLO property of large scale molecule. In present work, an effective intelligent computing method, as called extreme learning machine-neural network (ELM-NN), is proposed to predict accurately the first hyperpolarizability (beta(0)) of alkalides from low-accuracy first hyperpolarizability. Compared with neural network (NN) and genetic algorithm neural network (GANN), the root-mean square deviations of the predicted values obtained by ELM-NN, GANN, and NN with their MP2 counterpart are 0.02, 0.08, and 0.17 a.u., respectively. It suggests that the predicted values obtained by ELM-NN are more accurate than those calculated by NN and GANN methods. Another excellent point of ELM-NN is the ability to obtain the high accuracy level calculated values with less computing cost. Experimental results show that the computing time of MP2 is 2.4-4 times of the computing time of ELM-NN. Thus, the proposed method is a potentially powerful tool in computational chemistry, and it may predict beta(0) of the large scale molecules, which is difficult to obtain by high-accuracy theoretical method due to dramatic increasing computational cost. PMID- 22045550 TI - Hype and public trust in science. AB - Social scientists have begun elucidating the variables that influence public trust in science, yet little is known about hype in biotechnology and its effects on public trust. Many scholars claim that hyping biotechnology results in a loss of public trust, and possibly public enthusiasm or support for science, because public expectations of the biotechnological promises will be unmet. We argue for the need for empirical research that examines the relationships between hype, public trust, and public enthusiasm/support. We discuss the complexities in designing empirical studies that provide evidence for a causal link between hype, public trust, and public enthusiasm/support, but also illustrate how this may be remedied. Further empirical research on hype and public trust is needed in order to improve public communication of science and to design evidence-based education on the responsible conduct of research for scientists. We conclude that conceptual arguments made on hype and public trust must be nuanced to reflect our current understanding of this relationship. PMID- 22045551 TI - Second harmonic imaging of plants tissues and cell implosion using two-photon process in ZnO nanoparticles. AB - The optical properties of colloidal ZnO nanoparticle (NP) solutions, with size ranging from several nm to around 200 nm, have been tailored to have high optical nonlinearity for bioimaging with no auto-fluorescence above 750 nm and minimal auto-fluorescence below 750 nm. The high second harmonic conversion efficiency enables selective tissue imaging and cell tracking using tunable near-infrared femtosecond laser source ranging from 750-980 nm. For laser energies exceeding the two-photon energy of the bandgap of ZnO (half of 3.34 eV), the SHG signal greatly decreases and the two-photon emission becomes the dominant signal. The heat generated due to two-photon absorption within the ZnO NPs enable selective cell or localized tissue destruction using excitation wavelength ranging from 710 750 nm. PMID- 22045552 TI - Reduced pathological angiogenesis and tumor growth in mice lacking GPR4, a proton sensing receptor. AB - The G protein-coupled receptor GPR4 is activated by acidic pH and recent evidence indicates that it is expressed in endothelial cells. In agreement with these reports, we observe a high correlation of GPR4 mRNA expression with endothelial marker genes, and we confirm expression and acidic pH dependent function of GPR4 in primary human vascular endothelial cells. GPR4-deficient mice were generated; these are viable and fertile and show no gross abnormalities. However, these animals show a significantly reduced angiogenic response to VEGF (vascular endothelial growth factor), but not to bFGF (basic fibroblast growth factor), in a growth factor implant model. Accordingly, in two different orthotopic models, tumor growth is strongly reduced in mice lacking GPR4. Histological analysis of tumors indicates reduced tumor cell proliferation as well as altered vessel morphology, length and density. Moreover, GPR4 deficiency results in reduced VEGFR2 (VEGF Receptor 2) levels in endothelial cells, accounting, at least in part, for the observed phenotype. Our data suggest that endothelial cells sense local tissue acidosis via GPR4 and that this signal is required to generate a full angiogenic response to VEGF. PMID- 22045553 TI - Results of an Australian trial using SurePath liquid-based cervical cytology with FocalPoint computer-assisted screening technology. AB - BD FocalPoint GSTM computer-assisted screening of BD SurePath(r) liquid-based cervical cytology slides (SP + FP) was compared with screening an accompanying conventional cervical Papanicolaou (Pap) smear (CON) in a split sample trial of 2,198 routine specimens. The rate of unsatisfactory specimens in the SP + FP arm was 0.2% compared with 4.1% in the conventional Pap smear, a significant reduction. There was no statistically significant difference between SP + FP and CON for the detection of histologically confirmed high-grade (HG) lesions in the routine split sample specimens (n = 9). To further test the sensitivity of SP + FP for HG lesions, 38 SurePath slides from confirmed HG cases, without an accompanying CON, were interpolated among the routine smears. In every one of the 47 confirmed HG cases, either HG cells were present in the microscope fields selected by FocalPointGSTM for review by the screening cytologist (46 of 47), or full screening of the slide was indicated by the FocalPointGSTM (1 of 47), confirming the effectiveness of SP + FP technology for primary screening. In a small number of cases, the screening cytologist did not recognize the abnormality even though on review HG cells were present in fields selected by FocalPointGSTM. The overall detection rate was 93% for HG squamous lesions; 89% for known HG endocervical glandular lesions; and 91% for known endometrial carcinoma. In conclusion, the SP + FP detected 100% of HG abnormalities in the trial set; significantly reduced the rate of unsatisfactory specimens; and improved the overall screening rate of detection of HG abnormalities particularly of glandular lesions when compared with other screening technologies. PMID- 22045554 TI - Focal cortical lesion detection in multiple sclerosis: 3 Tesla DIR versus 7 Tesla FLASH-T2. AB - PURPOSE: To evaluate the inter-rater agreement of cortical lesion detection using 7 Tesla (T) FLASH-T2 and 3T DIR sequences. MATERIALS AND METHODS: Twenty-six patients with multiple sclerosis were scanned on a human 7T (Siemens) and 3T MRI (TIM Trio, Siemens) to acquire 3T DIR/MEMPR and 7T FLASH-T2 sequences. Four independent reviewers scored and categorized cortical lesions in the bilateral precentral gyri (motor strips) as leukocortical, intracortical, or subpial. Inter rater agreement was assessed according to lesion category using the kappa statistic. The sensitivity of recent MAGNIMS consensus guidelines for cortical lesion detection using 3T DIR was assessed with 7T FLASH-T2 as the reference gold standard. RESULTS: Inter-rater agreement at 7T was excellent compared with 3T (k = 0.97 versus 0.12). FLASH-T2 at 7T detected subpial lesions while 3T DIR did not. The predicted sensitivity of 3T DIR sequence for cortical lesions in vivo is modest (range of 13.6 to 18.3%). CONCLUSION: The 7T FLASH-T2 detects more cortical-particularly subpial-lesions compared with 3T DIR. In the absence of DIR/postmortem data, 7T FLASH-T2 is a suitable gold-standard instrument and should be incorporated into future consensus guidelines. PMID- 22045555 TI - Hormonal control of mammalian oocyte meiosis at diplotene stage. AB - Mammalian oocytes grow and undergo meiosis within ovarian follicles. Fully grown oocytes are arrested at the first meiotic prophase by a mural granulosa origin "arrester" until a surge of luteinizing hormone (LH) from the pituitary at the mid-cycle stimulates the immature oocyte to resume meiosis. Recent evidence indicates that natriuretic peptide precursor type C (NPPC) produced by mural granulosa cells stimulates the generation of cyclic guanosine 3',5'-monophosphate (cGMP) by cumulus cell natriuretic peptide receptor 2 (NPR2), which diffuses into oocyte via gap junctions and inhibits oocyte phosphodiesterase 3A (PDE3A) activity and cyclic adenosine 3',5'-monophosphate (cAMP) hydrolysis and maintains meiotic arrest with a high intraoocyte cAMP level. This cAMP is generated through the activity of the Gs G-protein by the G-protein-coupled receptor, GPR3 and GPR12, and adenylyl cyclases (ADCY) endogenous to the oocyte. Further studies suggest that endocrine hormones, such as follicle-stimulating hormone (FSH), LH, 17beta-estradiol (E2) and oocyte-derived paracrine factors (ODPFs), participate in oocyte meiosis possibly by the regulation of NPPC and/or NPR2. A detailed investigation of NPPC and NPR2 expression in follicle cells will elucidate the precise molecular mechanisms of gonadotropins, and control the arrest as well as resumption of meiosis. PMID- 22045556 TI - Regulation of neutrophil trafficking from the bone marrow. AB - Neutrophils are an essential component of the innate immune response and a major contributor to inflammation. Consequently, neutrophil homeostasis in the blood is highly regulated. Neutrophil number in the blood is determined by the balance between neutrophil production in the bone marrow and release from the bone marrow to blood with neutrophil clearance from the circulation. This review will focus on mechanisms regulating neutrophil release from the bone marrow. In particular, recent data demonstrating a central role for the chemokines CXCL12 and CXCL2 in regulating neutrophil egress from the bone marrow will be discussed. PMID- 22045559 TI - Analysis of protein ubiquitination. AB - Attachment of ubiquitin (Ub) to a protein requires a series of enzymes that recognize the substrate and promote Ub transfer. Several methods are described in this unit for determining if a protein has Ub-transferring activity. They include immunoblotting of immunoprecipitated proteins, affinity purification using His tagged Ub, assaying for auto-ubiquitination of E3, and assaying ubiquitination of a model substrate protein in vitro and in E. coli cells that express Ub-ligation enzymes. These methods are suitable for a variety of eukaryotic cells, but techniques are specifically described for use with yeast and mammalian cells. PMID- 22045557 TI - Polyreactive antibodies in adaptive immune responses to viruses. AB - B cells express immunoglobulins on their surface where they serve as antigen receptors. When secreted as antibodies, the same molecules are key elements of the humoral immune response against pathogens such as viruses. Although most antibodies are restricted to binding a specific antigen, some are polyreactive and have the ability to bind to several different ligands, usually with low affinity. Highly polyreactive antibodies are removed from the repertoire during B cell development by physiologic tolerance mechanisms including deletion and receptor editing. However, a low level of antibody polyreactivity is tolerated and can confer additional binding properties to pathogen-specific antibodies. For example, high-affinity human antibodies to HIV are frequently polyreactive. Here we review the evidence suggesting that in the case of some pathogens like HIV, polyreactivity may confer a selective advantage to pathogen-specific antibodies. PMID- 22045558 TI - Detection and analysis of proteins modified by O-linked N-acetylglucosamine. AB - O-GlcNAc is a common post-translational modification of nuclear, mitochondrial, and cytoplasmic proteins that is implicated in the etiology of type II diabetes and Alzheimer's disease, as well as cardioprotection. This unit covers simple and comprehensive techniques for identifying proteins modified by O-GlcNAc, studying the enzymes that add and remove O-GlcNAc, and mapping O-GlcNAc modification sites. PMID- 22045560 TI - Crystallization of macromolecules. AB - X-ray crystallography has evolved into a very powerful tool to determine the three-dimensional structure of macromolecules and macromolecular complexes. The major bottleneck in structure determination by X-ray crystallography is the preparation of suitable crystalline samples. This unit outlines steps for the crystallization of a macromolecule, starting with a purified, homogeneous sample. The first protocols describe preparation of the macromolecular sample (i.e., proteins, nucleic acids, and macromolecular complexes). The preparation and assessment of crystallization trials is then described, along with a protocol for confirming whether the crystals obtained are composed of macromolecule as opposed to a crystallization reagent. Next, the optimization of crystallization conditions is presented. Finally, protocols that facilitate the growth of larger crystals through seeding are described. PMID- 22045561 TI - Protein structural domains: definition and prediction. AB - Recognition and prediction of structural domains in proteins is an important part of structure and function prediction. This unit lists the range of tools available for domain prediction, and describes sequence and structural analysis tools that complement domain prediction methods. Also detailed are the basic domain prediction steps, along with suggested strategies for different protein sequences and potential pitfalls in domain boundary prediction. The difficult problem of domain orientation prediction is also discussed. All the resources necessary for domain boundary prediction are accessible via publicly available Web servers and databases and do not require computational expertise. PMID- 22045562 TI - Survey of protein engineering strategies. AB - Protein engineering is altering the structure of a protein to improve or change its properties. This unit summarizes concepts for protein engineering using rational design, directed evolution, and combinations of them. Different strategies are presented for identifying the best mutagenesis method, how to identify desired variants by screening or selection, and examples for successful applications are given. This should enable researchers to choose the most promising tools to solve their protein engineering challenges. PMID- 22045563 TI - Wayfinding: the effects of large displays and 3-D perception. AB - Large displays and stereopsis have been shown to improve performance in several virtual navigation tasks. In the present research, we sought to determine whether wayfinding could benefit from these factors. Participants were tested in a virtual town. There were three viewing conditions: a desktop, a large screen, and a large screen on which the virtual environment was viewed in three dimensions (3 D) using polarized glasses. Participants explored the town and had to remember the location of several landmarks. Their memory of the layout of the town was tested by asking them to navigate from one landmark to another, taking the shortest route possible. All groups performed equally well in terms of the distance traveled to target locations. From this result, we concluded that large displays and 3-D perception do not significantly contribute to wayfinding. Thus, experimental paradigms and training programs that utilize wayfinding are as valuable when administered on standard desktops as on more sophisticated and costly equipment and do not induce simulator sickness as large displays tend to do. PMID- 22045564 TI - Ultrasound in the investigation of posterior compartment vaginal prolapse and obstructed defecation. AB - Recent developments in diagnostic imaging have made gynecologists, colorectal surgeons and gastroenterologists realize as never before that they share a common interest in anorectal and pelvic floor dysfunction. While we often may be using different words to describe the same phenomenon (e.g. anismus/vaginismus) or attributing different meanings to the same words (e.g. rectocele), we look after patients with problems that transcend the borders of our respective specialties. Like no other diagnostic modality, imaging helps us understand each other and provides new insights into conditions we all need to learn to investigate better in order to improve clinical management. In this review we attempt to show what modern ultrasound imaging can contribute to the diagnostic work-up of patients with posterior vaginal wall prolapse, obstructed defecation and rectal intussusception/prolapse. In summary, it is evident that translabial/perineal ultrasound can serve as a first-line diagnostic tool in women with such complaints, replacing defecation proctography and MR proctography in a large proportion of female patients. This is advantageous for the women themselves because ultrasound is much better tolerated, as well as for healthcare systems since sonographic imaging is much less expensive. However, there is a substantial need for education, which currently remains unmet. PMID- 22045565 TI - Susceptibility of standard clones and European field populations of the green peach aphid, Myzus persicae, and the cotton aphid, Aphis gossypii (Hemiptera: Aphididae), to the novel anthranilic diamide insecticide cyantraniliprole. AB - BACKGROUND: Parthenogenetic clones of the green peach aphid, Myzus persicae (Sulzer), and the cotton aphid, Aphis gossypii Glover, were tested with the anthranilic diamide insecticide cyantraniliprole (i.e. DuPont(TM) Cyazypyr(TM) ) in systemic-uptake bioassays to investigate potential for cross-resistance conferred by mechanisms of insecticide resistance to organophosphates, carbamates and pyrethroids and, in the case of M. persicae, reduced sensitivity to neonicotinoids. These data were compared with the response of field samples of M. persicae and A. gossypii collected from around Europe. RESULTS: Cyantraniliprole was not cross-resisted by any of the known insecticide resistance mechanisms present in M. persicae or A. gossypii. The compound was equally active against resistant and susceptible aphid strains. The responses of the M. persicae field samples were very consistent with a maximum response ratio of 2.9 compared with a standard laboratory clone. The responses of the A. gossypii field samples were more variable, although a majority of the responses were not statistically different. CONCLUSION: Cyantraniliprole is currently the only anthranilic diamide (IRAC MoA 28) insecticide targeting aphid species such as M. persicae and A. gossypii. There is no evidence to suggest that the performance of this compound is affected by commonly occurring mechanisms that confer resistance to other insecticide chemistries. Cyantraniliprole is therefore a valuable tool for managing insecticide resistance in these globally important pests. PMID- 22045566 TI - Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload. AB - Iron overload is the hallmark of hereditary hemochromatosis and a complication of iron-loading anemias such as beta-thalassemia. Treatment can be burdensome and have significant side effects, and new therapeutic options are needed. Iron overload in hereditary hemochromatosis and beta-thalassemia intermedia is caused by hepcidin deficiency. Although transgenic hepcidin replacement in mouse models of these diseases prevents iron overload or decreases its potential toxicity, natural hepcidin is prohibitively expensive for human application and has unfavorable pharmacologic properties. Here, we report the rational design of hepcidin agonists based on the mutagenesis of hepcidin and the hepcidin-binding region of ferroportin and computer modeling of their docking. We identified specific hydrophobic/aromatic residues required for hepcidin-ferroportin binding and obtained evidence in vitro that a thiol-disulfide interaction between ferroportin C326 and the hepcidin disulfide cage may stabilize binding. Guided by this model, we showed that 7-9 N-terminal amino acids of hepcidin, including a single thiol cysteine, comprised the minimal structure that retained hepcidin activity, as shown by the induction of ferroportin degradation in reporter cells. Further modifications to increase resistance to proteolysis and oral bioavailability yielded minihepcidins that, after parenteral or oral administration to mice, lowered serum iron levels comparably to those after parenteral native hepcidin. Moreover, liver iron concentrations were lower in mice chronically treated with minihepcidins than those in mice treated with solvent alone. Minihepcidins may be useful for the treatment of iron overload disorders. PMID- 22045567 TI - CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in mice. AB - The two most common forms of inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis, affect approximately 1 million people in the United States. Uncontrolled APC reactivity toward commensal bacteria is implicated in the pathogenesis of the disease. A number of functionally distinct APC populations exist in the mucosal lamina propria (LP) below the intestinal epithelium, but their relative contributions to inflammation remain unclear. Here, we demonstrate in mice important roles for the chemokine receptor CX3CR1 in maintaining LP macrophage populations, preventing translocation of commensal bacteria to mesenteric lymph nodes (mLNs), and limiting colitogenic Th17 responses. CX3CR1 was found to be expressed in resident LP macrophages (defined as CD11b(+)F4/80(+)) but not DCs (defined as CD11c(+)CD103(+)). LP macrophage frequency and number were decreased in two strains of CX3CR1-knockout mice and in mice deficient in the CX3CR1 ligand CX3CL1. All these knockout strains displayed markedly increased translocation of commensal bacteria to mLNs. Additionally, the severity of DSS-induced colitis was dramatically enhanced in the knockout mice as compared with controls. Disease severity could be limited by either administration of neutralizing IL-17A antibodies or transfer of CX3CR1-sufficient macrophages. Our data thus suggest key roles for the CX3CR1/CX3CL1 axis in the intestinal mucosa; further clarification of CX3CR1 function will likely direct efforts toward therapeutic intervention for mucosal inflammatory disorders such as IBD. PMID- 22045569 TI - The debut of a rational treatment for an inherited neuropathy? AB - Hereditary neuropathies are common neurological conditions characterized by progressive loss of motor and/or sensory function. There are no effective treatments. Among the many causes of hereditary neuropathies are dominant mutations in serine palmitoyltransferase, long chain base subunit 1 (SPTLC1), which cause hereditary sensory and autonomic neuropathy type 1 (HSAN1). By incorporating L-alanine in place of L-serine, the mutant HSAN1-associated serine palmitoyltransferase generates deoxysphingolipids, which are thought to be neurotoxic. In this issue of the JCI, Garofalo and colleagues report that oral L serine reverses the accumulation of deoxysphingolipids in humans with HSAN1 and in a transgenic mouse model. As oral L-serine reduces the severity of neuropathy in the mouse model of HSAN1, these data suggest a rational candidate therapy for this devastating condition. PMID- 22045568 TI - NF-kappaB-inducing kinase plays an essential T cell-intrinsic role in graft versus-host disease and lethal autoimmunity in mice. AB - NF-kappaB-inducing kinase (NIK) is an essential upstream kinase in noncanonical NF-kappaB signaling. NIK-dependent NF-kappaB activation downstream of several TNF receptor family members mediates lymphoid organ development and B cell homeostasis. Peripheral T cell populations are normal in the absence of NIK, but the role of NIK during in vivo T cell responses to antigen has been obscured by other developmental defects in NIK-deficient mice. Here, we have identified a T cell-intrinsic requirement for NIK in graft-versus-host disease (GVHD), wherein NIK-deficient mouse T cells transferred into MHC class II mismatched recipients failed to cause GVHD. Although NIK was not necessary for antigen receptor signaling, it was absolutely required for costimulation through the TNF receptor family member OX40 (also known as CD134). When we conditionally overexpressed NIK in T cells, mice suffered rapid and fatal autoimmunity characterized by hyperactive effector T cells and poorly suppressive Foxp3(+) Tregs. Together, these data illuminate a critical T cell-intrinsic role for NIK during immune responses and suggest that its tight regulation is critical for avoiding autoimmunity. PMID- 22045570 TI - Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. AB - Hereditary sensory and autonomic neuropathy type 1 (HSAN1) causes sensory loss that predominantly affects the lower limbs, often preceded by hyperpathia and spontaneous shooting or lancinating pain. It is caused by several missense mutations in the genes encoding 2 of the 3 subunits of the enzyme serine palmitoyltransferase (SPT). The mutant forms of the enzyme show a shift from their canonical substrate L-serine to the alternative substrate L-alanine. This shift leads to increased formation of neurotoxic deoxysphingolipids (dSLs). Our initial analysis showed that in HEK cells transfected with SPTLC1 mutants, dSL generation was modulated in vitro in the presence of various amino acids. We therefore examined whether in vivo specific amino acid substrate supplementation influenced dSL levels and disease severity in HSAN1. In mice bearing a transgene expressing the C133W SPTLC1 mutant linked to HSAN1, a 10% L-serine-enriched diet reduced dSL levels. L-serine supplementation also improved measures of motor and sensory performance as well as measures of male fertility. In contrast, a 10% L alanine-enriched diet increased dSL levels and led to severe peripheral neuropathy. In a pilot study with 14 HSAN1 patients, L-serine supplementation similarly reduced dSL levels. These observations support the hypothesis that an altered substrate selectivity of the mutant SPT is key to the pathophysiology of HSAN1 and raise the prospect of l-serine supplementation as a first treatment option for this disorder. PMID- 22045571 TI - Cellular pathophysiology of ischemic acute kidney injury. AB - Ischemic kidney injury often occurs in the context of multiple organ failure and sepsis. Here, we review the major components of this dynamic process, which involves hemodynamic alterations, inflammation, and endothelial and epithelial cell injury, followed by repair that can be adaptive and restore epithelial integrity or maladaptive, leading to chronic kidney disease. Better understanding of the cellular pathophysiological processes underlying kidney injury and repair will hopefully result in the design of more targeted therapies to prevent the injury, hasten repair, and minimize chronic progressive kidney disease. PMID- 22045572 TI - Ceramides as modulators of cellular and whole-body metabolism. AB - Nearly all stress stimuli (e.g., inflammatory cytokines, glucocorticoids, chemotherapeutics, etc.) induce sphingolipid synthesis, leading to the accumulation of ceramides and ceramide metabolites. While the role of these lipids in the regulation of cell growth and death has been studied extensively, recent studies suggest that a primary consequence of ceramide accumulation is an alteration in metabolism. In both cell-autonomous systems and complex organisms, ceramides modify intracellular signaling pathways to slow anabolism, ensuring that catabolism ensues. These ceramide actions have important implications for diseases associated with obesity, such as diabetes and cardiovascular disease. PMID- 22045574 TI - Visual evaluation of different multifocal corneal models for the correction of presbyopia by laser ablation. AB - PURPOSE: To evaluate the visual quality of two theoretical multifocal corneal models designed to correct presbyopia by corneal photoablation. METHODS: Two theoretical multifocal corneal surfaces were analyzed by ray tracing: a central model (with a central zone for near vision and a peripheral zone for distance vision), and a peripheral model (with a central zone for distance vision and a peripheral zone for near vision). For both models, the effect of the size of the central zone and transition zone as well as the size of the pupil was evaluated. RESULTS: Our results show that a smaller transition zone favors total visual quality in both models. The optimal size of the central zone depends both on the size of the transition zone used as well as the model. However, both models responded similarly with respect to the variations in pupil size, providing the same visual quality although in an opposite way. CONCLUSIONS: This work shows that the optimal diameter of the central zone is smaller for the central model than for the peripheral model. Also, pupil size plays a fundamental role in achieving multifocality, showing that patient's pupil size should be thoroughly evaluated prior to multifocal refractive surgery. PMID- 22045575 TI - Validity of scaling zernike coefficients to a larger diameter for refractive surgery. AB - PURPOSE: To investigate the validity of a Zernike rescaling algorithm to a larger wavefront diameter. METHODS: Using 4256 preoperative wavefront examinations, the variability of inter-examination wavefront root-mean-square (RMS) was compared to the error induced due to scaling Zernike coefficients to a larger diameter. The validity of scaling Zernike coefficients was set when the error due to the scaling was the same as the variability of the inter-examination wavefronts. The inter-examination variability was calculated from eyes having at least 3 same day, preoperative examinations over the same diameters. Error from scaling Zernike coefficients to a larger diameter was calculated by comparing the wavefront for a (scaled-up) set of Zernike coefficients to the wavefront of the average of Zernike coefficient sets at a larger diameter for the same eye. Wavefront diameters of 5, 5.5, 6, 6.5, and 7 mm were considered. RESULTS: No significant difference was found for the variability for different pupil sizes. The error due to scaling Zernike coefficients to a larger pupil size was generally smaller than the inter-examination variability when the new diameter was 0.25 mm larger than the original diameter. The error was comparable to the inter-examination variability when the new diameter was 0.5 mm larger. The error became larger when the new diameter was >0.75 mm larger than the original diameter. CONCLUSIONS: Rescaling Zernike coefficients from a smaller diameter to a larger one has practical applications in optical zone extension for wavefront guided refractive surgery. PMID- 22045576 TI - Correction of presbyopia with a small aperture corneal inlay. AB - PURPOSE: To assess the efficacy of a small aperture corneal inlay (KAMRA, AcuFocus Inc) to improve near vision in emmetropic presbyopes. METHODS: Prospective, nonrandomized, multicenter clinical trial in presbyopic emmetropes aged 45 to 60 years. A small corneal pocket or flap was created in the nondominant eye by femtosecond laser or mechanical microkeratome, and the inlay (N=507) placed on the stromal bed. Uncorrected visual acuity was measured for the implanted eye at near (40 cm), intermediate (80 cm), and distance (20 ft) using ETDRS charts with the Optec 6500 Vision Tester (Stereo Optical Inc) at the preoperative, and 1-, 3-, 6-, 9-, 12-, and 18-month postoperative examinations. Contrast sensitivity (CS) was measured with best distance correction in the implanted eye using the Optec system and FACT chart under photopic (85 cd/m(2)) and mesopic (3 cd/m(2)) conditions preoperatively and at 1-year follow-up. RESULTS: Mean patient age was 52.87+/-3.64 years. Monocular mean uncorrected near visual acuity was J8 (0.482+/-0.925 logMAR) preoperatively, J3 (0.185+/-0.848 logMAR) at 1 month (n=506, P<.0001), and J2 (0.139+/-0.851 logMAR) at 18 months (n=99, P<.0001). Mean uncorrected intermediate visual acuity was 20/35 (0.239+/ 0.837 logMAR) preoperatively and 20/26 (0.139+/-0853 logMAR) at 18 months (P<.0001). Mean uncorrected distance visual acuity (UDVA) was 20/20 (0.011+/ 0.890 logMAR) at 18 months. Photopic (P<.001) and mesopic (P<.0001) monocular contrast sensitivities were within the range of the normal population at 1 year. CONCLUSIONS: The KAMRA corneal inlay improved near visual acuity with minimal impact on UDVA or mesopic contrast sensitivity in the implanted eye. PMID- 22045577 TI - Spherical aberrations of human astigmatic corneas. AB - PURPOSE: To evaluate whether the average spherical aberration of human astigmatic corneas is statistically equivalent to human nonastigmatic corneas. METHODS: Spherical aberrations of 445 astigmatic corneas prior to laser vision correction were retrospectively investigated to determine Zernike coefficients for central corneal areas 6 mm in diameter using CTView (Sarver and Associates). Data were divided into groups according to cylinder power (0.01 to 0.25 diopters [D], 0.26 to 0.75 D, 0.76 to 1.06 D, 1.07 to 1.53 D, 1.54 to 2.00 D, and >2.00 D) and according to age by decade. Spherical aberrations were correlated with age and astigmatic power among groups and the entire population. Statistical analyses were conducted, and P<.05 was considered statistically significant. RESULTS: Mean patient age was 42.6+/-11 years. Astigmatic corneas had an average astigmatic power of 0.78+/-0.58 D and mean spherical aberration was 0.25+/-0.13 MUm for the entire population and approximately the same (0.27 MUm) for individual groups, ranging from 0.23 to 0.29 MUm (P>.05 for all tested groups). CONCLUSIONS: Mean spherical aberration of astigmatic corneas was not correlated significantly with cylinder power or age (P>.05). Spherical aberrations are similar to those of nonastigmatic corneas, permitting the use of these additional data in the design of aspheric toric intra-ocular lenses. PMID- 22045578 TI - Concise review: Cancer stem cells and minimal residual disease. AB - Evidence gathered over the past two decades confirms earlier reports that suggested that hematologic malignancies exhibit a hierarchical differentiation structure similar to normal hematopoiesis. There is growing evidence that some solid tumors may also exhibit a differentiation program similar to the normal tissue of origin. Many excellent reviews on the topic of cancer stem cells (CSCs) document the recent explosion of information in the field, particularly highlighting the phenotypic and functional characteristics of these putative cells in vitro. Accordingly, here we only briefly discuss these concepts, and instead primarily examine the potential clinical relevance of CSCs, arguably the major unresolved issue in the field. Although it is generally accepted that CSCs are resistant to chemotherapy in vitro, only recently have data surfaced that suggest a role for these cells in disease relapse. Importantly, cancer cells with a stem cell phenotype have been found to be enriched in minimal residual disease of several malignancies. If the role of CSCs in relapse is confirmed, targeting these cells would hold substantial potential for improving the outcome of cancer patients. PMID- 22045579 TI - Relationships between surface-bound and internalized copper and cadmium and toxicity in Chlamydomonas reinhardtii. AB - In the present study, the adsorption and uptake of copper (Cu) and cadmium (Cd) in Chlamydomonas reinhardtii were examined to establish fundamental toxicity relationships to glutathione and cell-growth endpoints. Establishing these fundamental relationships of metal accumulation and toxicity metrics is necessary to subsequently implement an algal biotic ligand model. The glutathione response was similar to the response measured from growth endpoints for both internal and adsorbed Cu, indicating that glutathione may be a useful biomarker of toxicity. The glutathione response with Cd contrasted markedly with that observed with Cu and was therefore observed to be a metal-specific biomarker. The density of sites binding metals and the related stability constants for the algal cell surface were also determined. Short exposures to metals (2 h) were conducted, and we determined 6.0 * 10(-6) mol/g sites binding Cu and 2.0 * 10(-6) mol/g sites binding Cd and conditional stability constants as log K' = 7.2 and log K' = 6.7 for Cu and Cd, respectively. Experiments were also conducted to determine the effect on toxicity endpoints of varying nitrate concentrations and different humic acids (HA) in the exposure media. Varying nitrate concentrations did not have an effect on cell growth over 24 h. The surface-adsorbed Cu measurements from the experiments with HA depended on the type and concentration of HA. PMID- 22045580 TI - Minimally invasive non-thermal laser technology using laser-induced optical breakdown for skin rejuvenation. AB - We describe a novel, minimally invasive laser technology for skin rejuvenation by creating isolated microscopic lesions within tissue below the epidermis using laser induced optical breakdown. Using an in-house built prototype device, tightly focused near-infrared laser pulses are used to create optical breakdown in the dermis while leaving the epidermis intact, resulting in lesions due to cavitation and plasma explosion. This stimulates a healing response and consequently skin remodelling, resulting in skin rejuvenation effects. Analysis of ex-vivo and in-vivo treated human skin samples successfully demonstrated the safety and effectiveness of the microscopic lesion creation inside the dermis. Treatments led to mild side effects that can be controlled by small optimizations of the optical skin contact and treatment depth within the skin. The histological results from a limited panel test performed on five test volunteers show evidence of microscopic lesion creation and new collagen formation at the sites of the optical breakdown. This potentially introduces a safe, breakthrough treatment procedure for skin rejuvenation without damaging the epidermis with no or little social down-time and with efficacy comparable to conventional fractional ablative techniques. PMID- 22045582 TI - Safe use of hazardous chemicals. AB - This unit provides protocols for some commonly used disposal and decontamination procedures along with analytical techniques that are used to verify that reagents have been decontaminated. Some of the specific reagents covered are diaminobenzidine, ethidium bromide, cyanogen bromide, and chloromethylsilane. With modification, these assays may also be used to determine the concentration of a particular chemical. PMID- 22045581 TI - Proton MR spectroscopy in predicting the increase of perfusion MR imaging for WHO grade II gliomas. AB - PURPOSE: To investigate the correlation between the metabolite ratios obtained from proton magnetic resonance (MR) spectroscopy and those obtained from MR perfusion parameters (relative cerebral blood volume [rCBV]) in a cohort of low grade glioma (LGG). MATERIALS AND METHODS: Patients underwent prospectively conventional MR, proton magnetic resonance spectroscopy ((1) HMRS), and perfusion weighted images (PWI). Statistical analyses were performed to determine the correlative and independent predictive factors of rCBVmax and the metabolite ratio thresholds with optimum sensitivity and specificity. RESULTS: Thirty-one patients were included in this study. Linear correlations were observed between the metabolic ratios (lactate [Lac]/creatine [Cr], choline [Cho]/N-acetyl aspartate [NAA], free-lipids/Cr) and rCBVmax (P < 0.05). These metabolic ratios were determined to be independent predictive factors of rCBVmax (P = 0.027, 0.011 and 0.032, respectively). According to the receiver operating characteristic curves, the cutoff values of the metabolic ratios to discriminate between the two populations of rCBVmax (<1.7 versus = 1.7) were 1.72, 1.54, and 1.40, respectively, with a sensitivity = 75% and a specificity >95% for Lac/Cr. CONCLUSION: This study demonstrated consistent correlations between the data from (1) HMRS and PWI. The Lac/Cr ratio predicts regional hemodynamic changes, which are themselves a useful biomarker of clinical prognosis in patients with LGG. As such, this ratio may provide a new parameter for making improved clinical decisions. PMID- 22045583 TI - Methods for analysis of bacterial autoinducer-2 production. AB - Quorum sensing is a cell-cell signaling process that many bacteria use to regulate gene expression as a function of the density of the population. This phenomenon involves the production, release, and response to small chemical molecules termed autoinducers. Most autoinducers are species-specific; however, one autoinducer called autoinducer-2 (AI-2) is produced and detected by many species of bacteria and thus can foster inter-species communication. This unit describes two assays to detect and quantify AI-2 from biological samples. The first uses a bacterial reporter strain, which produces bioluminescence in response to AI-2. The second is an in vitro assay based on a modified version of an AI-2 receptor fused to a cyan fluorescent protein and a yellow fluorescent protein. Binding of AI-2 to this fusion protein induces a dose-dependent decrease in fluorescence resonance energy transfer (FRET), enabling quantification of the AI-2 concentration in the samples. PMID- 22045584 TI - Genetic Manipulation of Neisseria gonorrhoeae. AB - The sexually transmitted pathogen, Neisseria gonorrhoeae, undergoes natural transformation at high frequency. This property has led to the rapid dissemination of antibiotic resistance markers and to the panmictic structure of the gonococcal population. However, high-frequency transformation also makes N. gonorrhoeae one of the easiest bacterial species to manipulate genetically in the laboratory. Techniques have been developed that result in transformation frequencies >50%, allowing the identification of mutants by screening and without selection. Constructs have been created to take advantage of this high-frequency transformation, facilitating genetic mutation, complementation, and heterologous gene expression. Techniques are described for genetic manipulation of N. gonorrhoeae, as well as for growth of this fastidious organism. PMID- 22045585 TI - Extraction, purification, and identification of yersiniabactin, the siderophore of Yersinia pestis. AB - This unit describes in detail the extraction, purification, and identification of Yersiniabactin the siderophore of Yersinia pestis. Iron is essential for bacterial growth. Although relatively abundant, access to iron is limited in nature by low solubility. This problem is exacerbated for pathogenic bacteria, which must also defeat the host organism's innate defenses, including mechanisms to sequester iron. One solution to these problems is production of water soluble, small molecules with high affinities for iron called siderophores. This protocol has been fine tuned for Yersiniabactin purification but may be easily modified for use in isolating other siderophores or similar molecules. PMID- 22045586 TI - Vibriocidal assays to determine the antibody titer of patient sera samples. AB - The vibriocidal titer assay can be used to detect antibodies against Vibrio cholerae in serum samples, serving as an indicator of prior infection and potential protection against cholera. The assay can be utilized in research and clinical settings to test the effectiveness of vaccines, and also in epidemiological studies relevant to cholera transmission and surveillance. This unit outlines the steps involved in conducting an easily interpreted colorimetric vibriocidal titer assay with a relatively short turnaround time for results of around 8 hr, with final result observations in 24 hr. The assay can also be easily scaled up or down to accommodate as many or as few serum samples available and is not V. cholerae strain specific. PMID- 22045587 TI - Prevalence of levator ani muscle injury in Chinese women after first delivery. AB - OBJECTIVES: To assess the prevalence of levator ani muscle injury in Chinese women after their first delivery and investigate associated factors. METHODS: A prospective observational study was conducted involving Chinese nulliparous women recruited in the first trimester of pregnancy. Translabial ultrasound was performed at 35-38 weeks' gestation and 8 weeks postpartum and three-dimensional volume datasets were obtained. Offline analysis to detect levator ani muscle injury was performed by investigators blinded to the delivery details. RESULTS: 339 women, with a mean age of 30.6 +/- 3.9 years, completed the study. Overall, 201 (59.3%) had a spontaneous vaginal delivery, 62 (18.3%) an operative vaginal delivery (48 ventouse extraction and 14 forceps delivery), 14 (4.1%) an elective Cesarean section and 62 (18.3%) an emergency Cesarean section. No levator ani muscle injury was detected in any woman antenatally. After vaginal delivery, 57 (21.7% (95% CI, 16.7-26.7%)) women had levator ani muscle injury. The rates of injury for spontaneous vaginal delivery, ventouse extraction and forceps delivery were 15.4%, 33.3% and 71.4%, respectively. There was no levator ani muscle injury in the Cesarean section groups. Logistic regression analysis showed that only operative vaginal delivery (odds ratio, 3.09) was associated with an independent increase in the likelihood of levator ani muscle injury. Intrapartum epidural analgesics, duration of second stage of labor and infant birth weight were not independently associated with levator ani muscle injury. CONCLUSIONS: The prevalence of levator ani muscle injury in Chinese women after their first vaginal delivery was 21.7% (95% CI, 16.7-26.7%). Operative vaginal delivery was found to increase the likelihood of women suffering such injury. A longer follow up of these women and future studies on the effects of episiotomy are proposed. PMID- 22045588 TI - Strong resistance to the fungicide fenhexamid entails a fitness cost in Botrytis cinerea, as shown by comparisons of isogenic strains. AB - BACKGROUND: Fenhexamid, a sterol biosynthesis inhibitor effective against Botrytis, inhibits the 3-ketoreductase (Erg27) involved in C-4 demethylation. Several fenhexamid-resistant phenotypes have been detected in Botrytis cinerea populations from French vineyards. The field isolates with the highest resistance levels display amino acid changes in Erg27 (F412S, F412I or F412V). RESULTS: Fenhexamid-resistant mutants were generated by site-directed mutagenesis of the erg27 gene in a sensitive recipient strain to overcome the impact of different genetic backgrounds. The wild-type erg27 allele was replaced by the three mutated alleles (erg27(F412S/I/V)) by homologous recombination. These isogenic strains were shown to be fenhexamid-resistant and were used to quantify the impact of F412 mutations on fungal fitness. Several parameters, including radial growth, the production of sclerotia and conidia, freezing resistance and aggressiveness, were quantified in laboratory conditions. Analysis of variance demonstrated significant differences between the mutant and parental strains for some characters. In particular, the mutants grew more slowly than the wild-type strain and displayed variations in the production of sclerotia and conidia with temperature and susceptibility to freezing. CONCLUSIONS: The results highlight a moderate but significant impact of F412 mutations on the survival capacity of B. cinerea strains displaying high levels of resistance to fenhexamid in laboratory conditions, potentially limiting their dispersal and persistence, particularly in terms of overwintering, in field conditions. PMID- 22045590 TI - Semipreparative enantioseparation of methamidophos by HPLC-UV and preliminary in vitro study of butyrylcholinesterase inhibition. AB - Many chiral pesticides are introduced into the environment as racemates, although their pesticidal activity is usually the result of preferential reactivity of only one enantiomer, while the other enantiomer may have toxic effects against nontarget organisms. Methamidophos (O,S-dimethyl phosphoramidothioate), a chiral compound, is an insecticide widely used in agriculture in both developed and developing countries. However, this pesticide has a high toxicity not only to targeted insects but also to human and animals. In the present study, the enantiomers of methamidophos were enantiomerically separated by a semipreparative chiral liquid chromatography at the multimilligram scale on a polysaccharide based chiral stationary phase and a preliminary evaluation of their in vitro inhibition of plasma butyrylcholinesterase (BChE) of hens was performed. In the present study, our first effort was to resolve the racemic mixture of methamidophos and to that end reversed-phase, normal-phase, and polar organic elution conditions were investigated in four different polysaccharide-based chiral phases. The best performance was achieved on a cellulose tris(3,5 dimethylphenylcarbamate) phase under normal phase. This chromatographic condition allowed the separation of 225 mg of methamidophos enantiomers with a high degree of chiral purity (>98%) in a short analysis time. Significant differences were found between the concentration that causes 50% of enzyme inhibition (IC50) of the three isoforms of methamidophos. (-)-Methamidophos showed an IC50 approximately three times larger than the (+)-enantiomer for plasma BChE of hens. PMID- 22045589 TI - Characterization and function of histamine receptors in human bone marrow stromal cells. AB - There are several clinical trials worldwide using bone marrow stromal cells (BMSCs) as a cellular therapy to modulate immune responses in patients suffering from various inflammatory conditions. A deeper understanding of the molecular mechanisms involved in this modulatory effect could help us design better, more effective protocols to treat immune mediated diseases. In this study, we demonstrated that human BMSCs express H1, H2, and H4 histamine receptors and they respond to histamine stimulation with an increased interleukin 6 (IL-6) production both in vitro and in vivo. Using different receptor antagonists, we pinpointed the importance of the H1 histamine receptor, while Western blot analysis and application of various mitogen-activated protein kinase inhibitors highlighted the role of p38, extracellular signal-regulated kinase, and c-Jun N terminal kinase kinases in the observed effect. When BMSCs were pretreated with either histamine or degranulated human mast cells, they exhibited an enhanced IL 6-dependent antiapoptotic effect on neutrophil granulocytes. Based on these observations, it is likely that introduction of BMSCs into a histamine-rich environment (such as any allergic setting) or pretreatment of these cells with synthetic histamine could have a significant modulatory effect on the therapeutic potential of BMSCs. PMID- 22045591 TI - Reducing the cost of production of bimetallic aluminium catalysts for the synthesis of cyclic carbonates. AB - Bimetallic aluminium complexes of general formula [(salen)Al](2)O or [(acen)Al](2)O catalyse the formation of cyclic carbonates from carbon dioxide and terminal epoxides under exceptionally mild reaction conditions. To improve the potential for industrial scale application of these catalysts, the cost of their production has been evaluated and reduced significantly by optimization of the synthesis, including replacement of the most expensive chemicals by less expensive alternatives. The largest cost saving was associated with the formation of aluminium triethoxide in situ, which reduced the cost of the chemicals need for production of the catalysts by 49-87 %. Further savings were made by avoiding the use of tetrabutylammonium bromide and acetonitrile, resulting in overall cost savings of 68-93 %. PMID- 22045592 TI - A longitudinal MRI study of muscle atrophy during lower leg immobilization following ankle fracture. AB - PURPOSE: To investigate MRI biomarkers of muscle atrophy during cast immobilization of the lower leg. MATERIALS AND METHODS: Eighteen patients (8 male, 10 female), who had one lower leg immobilized in a cast, underwent 3.0 Tesla (T) MR imaging 5, 8, 15, 29, and 43 days after casting. Measurements were made on both lower legs of total muscle volume. Cross-sectional area (CSA), fractional water content, and T(2) were measured in tibialis anterior (TA), gastrocnemius medialis (GM) and lateralis (GL) and soleus (SOL). Fiber pennation angle was measured in GM. RESULTS: Total muscle volume decreased by 17% (P < 0.001) over the 6 weeks of immobilization. The greatest loss in CSA (mean[SD]) was seen in GM (-23.3(8.7)%), followed by SOL (-19.0(9.8)%), GL (-17.1(6.5)%), and TA (-10.7(5.9)%). Significant reductions of CSA were also detectable in the contra-lateral leg. T(2) increased in all muscles: TA 27.0(2.5) ms to 29.6(2.8) ms (P < 0.001), GM 34.6(2.9) ms to 39.8(5.4) ms (P < 0.001) and SOL 34.4 (2.9) ms to 44.9(5.9) ms (P < 0.001). Small reductions were found in fractional water content. Pennation angle decreased in the cast leg (P < 0.001). CONCLUSION: Quantitative MR imaging can detect and monitor progressive biochemical and biophysical changes in muscle during immobilization. PMID- 22045593 TI - Use of processed pericardium graft to plug patulous old sclerostomy track during glaucoma shunt revision for exposure. AB - The authors demonstrate a reproducible technique using processed pericardium to seal sclerostomy track during glaucoma shunt revision. The suggested method involves placement of a wedge-shaped processed pericardial graft into the old sclerostomy tract following tube explantation. The graft is trimmed and sutured to the sclera. The tube is reinserted into a new sclerostomy and then sutured in place and covered in the usual fashion. This method allowed relatively easy treatment of three patients with patulous sclerostomy with necrotic edges. A successful tube revision and repositioning of the tube using this technique was performed on three patients with exposed tubes. The intraocular pressure was between 8 and 12 mm Hg from postoperative day 1. The authors suggest the use of pericardium plug to adequately seal the old sclerostomy track during glaucoma shunt revision. The plug allows tube repositioning at a new site without the need to suture the friable sclerostomy edges. PMID- 22045594 TI - Inter- and intraobserver variability in three-dimensional ultrasound assessment of the endometrial-myometrial junction and factors affecting its visualization. AB - OBJECTIVE: To assess the inter- and intraobserver variability of three dimensional (3D) ultrasound assessment of the endometrial-myometrial junction (EMJ), and to assess demographic and physiological factors that affect the quality of its imaging. METHODS: Women attending our gynecology clinic, who were deemed to have normal uteri on transvaginal ultrasound examination, were enrolled in this prospective study. They underwent 3D volume acquisition of the entire uterus in order to acquire a coronal view of the organ. Visualization of EMJs was classified as optimal, satisfactory or unsatisfactory. In order to assess the intra- and interobserver variabilities of the classification system, the volumes were classified by two independent observers on two separate occasions. The same classification system was then used to evaluate the EMJs of 101 women who were deemed to have normal uteri on transvaginal ultrasound examination. The results were correlated with age, parity, stage of cycle, menopausal status and endometrial thickness in order to assess whether any of these factors affect visualization of the EMJ. RESULTS: A total of 30 uterine volumes were examined in the first analysis. Both the inter- and intraobserver variability were good (kappa values of 0.77 and 0.83). Of the 101 EMJs assessed in the second analysis, 47 were classified as optimal, 42 as satisfactory and 12 as unsatisfactory. Endometrial thickness was positively associated with EMJ visualization and parity was negatively associated with EMJ visualization. CONCLUSIONS: Assessment of EMJ visualization has both good inter- and intraobserver variability in women with normal uteri. Parity and endometrial thickness have contrasting, statistically significant, effects on visualization of the EMJ. PMID- 22045595 TI - Randomized double-blind phase 2 trial of 3 doses of TAS-108 in patients with advanced or metastatic postmenopausal breast cancer. AB - BACKGROUND: The objective of this study was to evaluate 3 different doses of (7alpha)-21-(4-[(diethylamino)methyl]-2 methoxyphenoxy)-7 methyl-19 norpregna 1,3,5(10)-trien-3-ol 2-hydroxy-1,2,3-propanetricarboxylate (TAS-108) in patients with recurrent, hormone-responsive breast cancer. METHODS: In this randomized, double-blind, multicenter study, TAS-108 was administered daily at a dose of 40 mg, 80 mg, or 120 mg to postmenopausal patients with locally advanced, or inoperable, or metastatic hormone-receptor positive breast cancer. The primary efficacy outcome was clinical benefit (CB), defined as the total number of patients who achieved a complete response, a partial response, or stable disease for >=24 weeks. The study was a 2-stage design in which 19 patients per dose group were planned in the first stage. If at least 3 patients in any dose group achieved a CB, then that dose group was to be allowed to continue enrolling for the second stage, and the group could include up to a total of 60 patients. RESULTS: The 40-mg and 80-mg groups met the criterion and enrolled patients into the second stage. In the 40-mg group, there were 13 CB events in 60 patients (21.7%); and, in the 80-mg group, there were 12 CB events in 60 patients (20%). The 120-mg daily dose was stopped early, because it failed to achieve the criterion. For the 40-mg and 80-mg groups, the median time to progression was 15.0 weeks and 15.9 weeks, respectively. Only 1 drug-related serious adverse event (grade 3 hyperglycemia) was reported. CONCLUSIONS: TAS-108 at 40 mg and 80 mg daily demonstrated clinical activity with an encouraging duration of benefit. Because of its superior safety profile, TAS-108 40 mg daily is recommended for further development. PMID- 22045596 TI - Ketamine induces motor neuron toxicity and alters neurogenic and proneural gene expression in zebrafish. AB - Ketamine, a noncompetitive antagonist of N-methyl-d-aspartate-type glutamate receptors, is a pediatric anesthetic that has been shown to be neurotoxic in rodents and nonhuman primates when administered during the brain growth spurt. Recently, the zebrafish has become an attractive model for toxicity assays, in part because the predictive capability of the zebrafish model, with respect to chemical effects, compares well with that from mammalian models. In the transgenic (hb9:GFP) embryos used in this study, green fluorescent protein (GFP) is expressed in the motor neurons, facilitating the visualization and analysis of motor neuron development in vivo. In order to determine whether ketamine induces motor neuron toxicity in zebrafish, embryos of these transgenic fish were treated with different concentrations of ketamine (0.5 and 2.0 mm). For ketamine exposures lasting up to 20 h, larvae showed no gross morphological abnormalities. Analysis of GFP-expressing motor neurons in the live embryos, however, revealed that 2.0 mm ketamine adversely affected motor neuron axon length and decreased cranial and motor neuron populations. Quantitative reverse transcriptase polymerase chain reaction analysis demonstrated that ketamine down-regulated the motor neuron-inducing zinc finger transcription factor Gli2b and the proneural gene NeuroD even at 0.5 mm concentration, while up-regulating the expression of the proneural gene Neurogenin1 (Ngn1). Expression of the neurogenic gene, Notch1a, was suppressed, indicating that neuronal precursor generation from uncommitted cells was favored. These results suggest that ketamine is neurotoxic to motor neurons in zebrafish and possibly affects the differentiating/differentiatedneurons rather than neuronal progenitors. Published 2011. This article is a US Government work and is in the public domain in the USA. PMID- 22045597 TI - Adsorption, transport and degradation of fipronil termiticide in three Hawaii soils. AB - BACKGROUND: The behavior of the termiticide fipronil in soils was studied to assess its potential to contaminate ground and surface water. This study characterizes (1) adsorption of fipronil in three different soils, (2) transport of fipronil through leaching and runoff under simulated rainfall in these soils and (3) degradation of fipronil to fipronil sulfide and fipronil sulfone in these soils. RESULTS: The adsorption experiments showed a Freundlich isotherm for fipronil with K(oc) equal to 1184 L kg(-1) . In the leaching experiments, the concentration of fipronil and its metabolites in leachate and runoff decreased asymptotically with time. The concentration of fipronil in the leachate from the three soils correlated inversely with soil organic carbon content. The degradation experiment showed that the half-life of fipronil in the soils ranged from 28 to 34 days when soil moisture content was 75% of field capacities, and that 10.7-23.5% of the degraded fipronil was transformed into the two metabolites (fipronil sulfide and fipronil sulfone). CONCLUSION: Fipronil showed large losses through leaching but small losses via runoff owing to low volumes of runoff water generated and/or negligible particle-facilitated transport of fipronil. The half life values of fipronil in all three soils were similar. PMID- 22045598 TI - The role of human leukocyte antigen matching in the development of multiethnic "haplobank" of induced pluripotent stem cell lines. AB - Among the tools of regenerative medicine, induced pluripotent stem cells (iPSCs) are interesting because the donor genotype can be selected. The construction of banks of iPSC cell lines selected from human leukocyte antigen (HLA) homozygous donors has been proposed to be an effective way to match a maximal number of patients receiving cell therapy from iPSC lines. However, what effort would be required to constitute such a bank for a worldwide application has remained unexplored. We developed a probabilistic model to compute the number of donors to screen for constituting banks of best-chosen iPSC lines with homozygous HLA haplotypes (haplobanks) in four ancestry backgrounds. We estimated what percentage of the patients would be provided with single HLA haplotype matched cell lines. Genetic diversity leads to different outcomes for the four sets in all terms. A bank comprising iPSC lines representing the 20 most frequent haplotypes in each population would request quite different number of donors to screen, between 26,000 for European Americans and 110,000 for African Americans. It would also match different fractions of the recipient population, namely, more than 50% of the European Americans and 22% of African Americans. Conversely, a bank comprising the 100 iPSC lines with the most frequent HLA in each population would leave out only 22% of the European Americans, but 37% of the Asians, 48% of the Hispanics, and 55% of the African Americans. The constitution of a haplobank of iPSC lines is achievable through a large-scale concerted worldwide collaboration. PMID- 22045599 TI - Effective production of octane from biomass derivatives under mild conditions. PMID- 22045600 TI - Metabolism and distribution of p,p'-DDT during flight of the white-crowned sparrow, Zonotrichia leucophrys. AB - This study evaluated the interactions of flight, fasting, and 1,1,1-trichloro bis(4-chlorophenyl)ethane (p,p'-DDT) loading on residue metabolism and distribution in recently exposed white-crowned sparrows (Zonotrichia leucophrys). Female sparrows were dosed with 5 mg p,p'-DDT per kg body weight over 3 d. Following 1 d of recovery, sparrows were flown in a wind tunnel for up to 140 min, in 15-min blocks. Food was withheld from the start of the flight period until birds were euthanized. DDT, 1,1-dichloro-2,2-bis(4 chlorophenyl)ethane (DDD), and 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (DDE) were present in all tissues examined. 1-Chloro-2,2-bis(4-chlorophenyl)ethene (DDu), 1,1-bis(4 chlorophenyl)ethane (p,p'-DDeta), and 2,2-bis(4-chlorophenyl)ethanol (p,p'-DDOH) were not found. Fasting did not significantly affect the rate of residue increase over time in any of the tissues examined. When sparrows flew and fasted simultaneously, fasting seldom contributed to an increase in tissue residues. However, the length of time flown was significantly correlated with increasing toxicant concentrations in the brain, kidney, and liver, effectively demonstrating the potential for brief flights to enhance mobilization of DDT and its metabolites. Dose, flight, and fasting also increased residues in brain tissue. These contaminant redistributions may have important ramifications on the stresses experienced by migratory birds. PMID- 22045601 TI - Measuring T2 in vivo with J-difference editing: application to GABA at 3 Tesla. AB - PURPOSE: To develop an experimental approach for determining in vivo transverse relaxation rates (T(2)) of metabolites that are detected by spectral editing without using simulations, and to demonstrate this approach to measure the T(2) of gamma-aminobutyric acid (GABA). MATERIALS AND METHODS: The proposed method first determines the TE-dependence of the edited signals using measurements in a pure phantom solution (10 mM gamma-aminobutyric acid; GABA); the phantom T(2) is also determined. Once the editing echo time (TE)-modulation pattern is known, it can then be used to determine T(2) in vivo. The method was applied to measure GABA T(2) in the occipital lobe of five healthy adult subjects at 3T, using a J difference editing method. Unwanted macromolecular contributions to the GABA signal were also measured. RESULTS: The in vivo T(2) of edited GABA signal was 88 +/- 12 ms; this preliminary result is somewhat shorter than other metabolite T(2) values in the literature at this field strength. CONCLUSION: Spectral editing methods are now widely used to detect low concentration metabolites, such as GABA, but to date no edited acquisition methods have been proposed for the measurement of transverse relaxation times (T(2)). The method described has been successfully applied to measuring the T(2) of GABA. PMID- 22045602 TI - Too cold for comfort: a neonate with severe hypothermia. AB - Severe neonatal hypothermia is an infrequent presentation to the Emergency Department. This case report describes the successful resuscitation and rapid rewarming of a newborn baby who presented to the Emergency Department with a core temperature of 14.8 degrees C. This is the lowest temperature documented in the literature to date from which an infant has been successfully resuscitated. PMID- 22045603 TI - A 76-year-old man with progressive lower back pain and right thigh swelling. PMID- 22045604 TI - The National Falls and Bone Health Audit: implications for UK emergency care. AB - INTRODUCTION: The National Clinical Audit of Falls and Bone Health, coordinated by the Royal College of Physicians, assesses progress in implementing integrated falls services across the UK against national standards and enables benchmarking between service providers. Nationally, falls are a leading contributor towards mortality and morbidity in older people and account for 700,000 visits to emergency departments and 4 million annual bed days in England alone. METHODS: Two rounds of national organisational audit in 2005 and 2008 and one national clinical audit in 2006 were carried out based on indicators developed by a multidisciplinary group. RESULTS: These showed that management of falls and bone health in older people remains suboptimal in emergency departments and minor injury units and opportunities are being missed in carrying out evidence-based risk assessment and management. CONCLUSIONS: Older people attending emergency departments in the UK following a fall are receiving a poor deal. There is an urgent need to ensure more effective assessment and management to prevent further falls and fractures. PMID- 22045605 TI - Basic life support skill retention of medical interns and the effect of clinical experience of cardiopulmonary resuscitation. AB - OBJECTIVE: To investigate the level of basic life support (BLS) skill retention of medical interns 6 and 12 months after BLS education and analyse the correlation between clinical experience of cardiopulmonary resuscitation (CPR) and BLS skill retention. MATERIALS AND METHODS: The baseline performance of BLS skills in medical doctors during their internship was tested immediately after the BLS provider course. The subjects were divided into two groups, which were tested using the same method after 6 months or after 12 months. Data on the subjects' CPR experience were collected through CPR records--specifically, the number of CPR experiences and the feedback given by the CPR team leaders. To evaluate BLS skill retention, baseline BLS skill performance was compared with the skill performances measured after 6 or 12 months. RESULTS: Fifty-six subjects were enrolled in the 6 month group and 36 in the 12 month group. For non compression skills, the points for skills declined from 12 to 6 points in the 6 month group and from 12 to 6 points in the 12 month group and the declines in both groups were statistically significant. For compression skills, in the 12 month group, the hands-off time improved from 9.9 s to 8.7 s, with statistical significance. In the multivariate linear regression test, the number of times feedback was given had a statistical relationship with improvement in hands-off time in the 12 month group (coefficient 0.58, 95% CI 0.12 to 1.05). CONCLUSIONS: In medical doctors, the compression skills were well preserved, but the retention of non-compression skills was poor. PMID- 22045606 TI - Short answer question case series: a fatal case of swelling. PMID- 22045607 TI - Accuracy of a feedback device for cardiopulmonary resuscitation on a dental chair. AB - BACKGROUND: Conflicting studies exist about the effectiveness of cardiopulmonary resuscitation (CPR) on a dental chair. In some situations, dental surgeons are obliged to perform CPR with the patient on the chair. Feedback devices are supposed to guide the compression depth in order to improve the quality of CPR, but some devices are based on an accelerometer that can theoretically report erroneous results because of the lack of rigidity of a dental chair. OBJECTIVE: The aim of this study was to evaluate the accuracy of these devices to guide chest compressions on a dental chair. METHODS: A prospective, randomised, crossover, equivalence/non-inferiority study was conducted to compare the values of compression depths provided by the feedback device (Real CPR Help((r)), delivered by Zoll(c) Medical Corporation, Chelmsford, MA, USA) with the real measurements provided by the manikin (Resusci Anne((r)) Advanced SkillTrainer, Laerdal Medical AS(c), Norway). Chest-compression-only CPR was performed by 15 Basic Life Support instructors who carried out two rounds of continuous CPR for 2 min each. Data were analysed with a correlation test, a Bland-Altman method and a Wilcoxon test. Statistical significance was defined as p<0.05. RESULTS: A significant difference was found between the mean depths of compression measured by the feedback device and the manikin on a dental chair and on the floor (p<0.0001). The feedback device overestimated the depth of chest compressions, and Bland-Altman analysis demonstrated poor agreement. CONCLUSION: This study indicates that feedback devices with accelerometer technology are not sufficiently reliable to ensure adequate chest compression on dental chairs. PMID- 22045608 TI - Variability in cardiac arrest survival: the NHS Ambulance Service Quality Indicators. PMID- 22045609 TI - Are we ready? Preparedness of acute care providers for the Rugby World Cup 2011 in New Zealand. AB - New Zealand is hosting the Rugby World Cup (RWC) 2011. It is the largest sporting event in New Zealand's history, with around 70,000 fans estimated to visit the country from September to October 2011. This influx of tourists will have an impact on its already stretched healthcare services. The preparedness of New Zealand's healthcare system to handle this mass event is unclear. OBJECTIVES: The two main objectives of this study were (1) to determine the perceived preparedness of acute care providers in New Zealand to respond to the healthcare demands of RWC 2011; and (2) to determine the factors associated with perceived strong preparedness among acute care providers in New Zealand. METHOD: A cross sectional survey of 1500 doctors, nurses and ambulance officers working in acute care services in New Zealand was conducted between June 2010 and March 2011. RESULTS: 911 surveys were completed (response rate 60.7%). Only 12.7% of acute care providers felt they were prepared to deal with possible health issues arising from RWC 2011. Perceived preparedness was highest among ambulance officers and lowest among providers in intensive care units (16.3% vs 4.1%, p<0.01). Acute care providers who were aware of their role in a mass emergency were more likely to report preparedness with a prevalence OR of 3.5 and a 95% CI of 2.1 to 5.7. CONCLUSION: Only 12.7% of acute care providers in New Zealand perceived preparedness for RWC 2011. Perceived preparedness followed a stepwise decline from prehospital services, emergency department, to surgery and then finally to intensive care services. This indicates that current preparedness activities are focusing on prehospital emergency services and neglecting surgical and intensive care services. Awareness about the role of acute care providers during emergencies, training and previous experience were associated with perceived strong preparedness for RWC 2011. PMID- 22045610 TI - Ensuring quality cancer care: a follow-up review of the Institute of Medicine's 10 recommendations for improving the quality of cancer care in America. AB - Responding to growing concerns regarding the safety, quality, and efficacy of cancer care in the United States, the Institute of Medicine (IOM) of the National Academy of Sciences commissioned a comprehensive review of cancer care delivery in the US health care system in the late 1990s. The National Cancer Policy Board (NCPB), a 20-member board with broad representation, performed this review. In its review, the NCPB focused on the state of cancer care delivery at that time, its shortcomings, and ways to measure and improve the quality of cancer care. The NCPB described an ideal cancer care system in which patients would have equitable access to coordinated, guideline-based care and novel therapies throughout the course of their disease. In 1999, the IOM published the results of this review in its influential report, Ensuring Quality Cancer Care. The report outlined 10 recommendations, which, when implemented, would: 1) improve the quality of cancer care, 2) increase the current understanding of quality cancer care, and 3) reduce or eliminate access barriers to quality cancer care. Despite the fervor generated by this report, there are lingering doubts regarding the safety and quality of cancer care in the United States today. Increased awareness of medical errors and barriers to quality care, coupled with escalating health care costs, has prompted national efforts to reform the health care system. These efforts by health care providers and policymakers should bridge the gap between the ideal state described in Ensuring Quality Cancer Care and the current state of cancer care in the United States. PMID- 22045611 TI - Ultrastructural analysis of implant-soft tissue interface on a three dimensional tissue-engineered oral mucosal model. AB - A three dimensional tissue-engineered human oral mucosal model (3D OMM) used in the investigation of implant-soft tissue interface was recently reported. The aim of this study was to examine the ultrastructural features of soft tissue attachment to various titanium (Ti) implant surfaces based on the 3D OMM. Two techniques, that is, focus ion beam (FIB) and electropolishing techniques were used to prepare specimens for transmission electron microscopic (TEM) analysis of the interface. The 3D OM consisting of both epithelial and connective tissue layers was constructed by co-culturing human oral keratinocytes and fibroblasts onto an acellular dermis scaffold. Four types of Ti surface topographies were tested: polished, machined (turned), sandblasted, and TiUnite. The specimens were then processed for TEM examination using FIB (Ti remained) and electropolishing (Ti removed) techniques. The FIB sections showed some artifact and lack of details of ultrastructural features. In contrast, the ultrathin sections prepared from the electropolishing technique showed a residual Ti oxide layer, which preserved the details for intact ultrastructural interface analysis. There was evidence of hemidesmosome-like structures at the interface on the four types of Ti surfaces, which suggests that the tissue-engineered oral mucosa formed epithelial attachments on the Ti surfaces. PMID- 22045612 TI - 'Long-term feeding effects of stevioside sweetener on some toxicological parameters of growing rats'. PMID- 22045614 TI - Cancer-associated nummular loss of RPE: expanding the clinical spectrum of bilateral diffuse uveal melanocytic proliferation. AB - This report describes a case of cancer-associated nummular retinal pigment epithelium loss associated with uterine cancer. The patient had progressive visual loss despite treatment with plasmapheresis, intravenous immunoglobulin, and local injection of corticosteroids. Clinical deterioration was corroborated by extension of the areas of retinal pigment epithelium loss, progression of cataracts, and growth of pigmented choroidal and iris lesions. Previously published cases of cancer-associated nummular retinal pigment epithelium loss did not describe the presence of cataracts or uveal melanocytic lesions. This case expands the clinical spectrum of bilateral diffuse uveal melanocytic proliferation. PMID- 22045613 TI - Notch signaling is necessary to maintain quiescence in adult muscle stem cells. AB - Satellite cells (SCs) are myogenic stem cells found in skeletal muscle that function to repair tissue damaged by injury or disease. SCs are quiescent at rest, although the signaling pathways required to maintain quiescence are unknown. Using a transgenic Notch reporter mouse and quantitative reverse transcription polymerase chain reaction analysis of Notch target genes, we determined that Notch signaling is active in quiescent SCs. SC-specific deletion of recombining binding protein-Jkappa (RBP-Jkappa), a nuclear factor required for Notch signaling, resulted in the depletion of the SC pool and muscles that lacked any ability to regenerate in response to injury. SC depletion was not due to apoptosis. Rather, RBP-Jkappa-deficient SCs spontaneously activate, fail to self renew, and undergo terminal differentiation. Intriguingly, most of the cells differentiate without first dividing. They then fuse with adjacent myofibers, leading to the gradual disappearance of SCs from the muscle. These results demonstrate the requirement of Notch signaling for the maintenance of the quiescent state and for muscle stem cell homeostasis by the regulation of self renewal and differentiation, processes that are all critical for normal postnatal myogenesis. PMID- 22045615 TI - Role of ancillary studies in fine-needle aspiration from selected tumors. AB - The routine use of ancillary studies is reshaping the practice of cytopathology. Currently, most cytopathologists recognize the importance of immunocytochemistry and molecular techniques as adjuncts to morphology to achieve a precise diagnosis. Cytopathologists also are expected to include specific prognostic and predictive information in their reports. The objective of this review was to address the use of immunocytochemistry and molecular techniques to refine the preoperative diagnosis and classification of lung cancer, thyroid cancer, kidney cancer, gastrointestinal cancer, and soft tissue tumors. Fine-needle aspiration also offers a suitable alternative to biopsy in a variety of clinical settings, in particular, when it may be useful to obtain material to study prognostic and predictive markers. This is particularly relevant to obtain material from metastatic sites. The study of KRAS in colon cancer, CKIT in gastrointestinal stromal tumors, and epidermal growth factor receptor mutational status in lung cancer also are addressed particularly in this report. PMID- 22045616 TI - Assessing environmental contamination around obsolete pesticide stockpiles in West Africa: using the Nile monitor (Varanus niloticus) as a sentinel species. AB - Environmental contamination caused by obsolete pesticide stocks was assessed using the Nile monitor (Varanus niloticus) as a sentinel species. Organochlorines and organophosphates were quantified by gas chromatography in abdominal fat and the liver, respectively. Results were compared to those obtained from three other sites, characterized by different histories of contamination. None of the previously stocked pesticides were recovered. Low to moderate levels of 4,4' dichlorodiphenyldichloroethylene (4,4'-DDE) were quantified in monitors from all sites. Malathion and 4,4'-dichlorodiphenyldichloroethane (4,4'-DDD) also were detected sporadically. Interindividual variability was substantial. Correlations between pesticide loads and individual characteristics were considered. The nondetection of previously stocked pesticides in the monitors' tissues, their contamination by other pesticides, and the value of V. niloticus as a monitoring tool for environmental contamination are discussed. The results indicate a situation of low concern and draw attention to the importance of local conditions in determining environmental dangers associated with potential pollution sources. PMID- 22045617 TI - MR elastography of the in vivo abdominal aorta: a feasibility study for comparing aortic stiffness between hypertensives and normotensives. AB - PURPOSE: To demonstrate feasibility of using MR elastography (MRE) to identify hypertensive changes in the abdominal aorta when compared with normotensives based on the stiffness measurements. MATERIALS AND METHODS: MRE was performed on eight volunteers (four normotensives and four hypertensives) to measure the effective stiffness of the abdominal aorta. MRE wave images are directionally filtered and phase gradient analysis was performed to determine the stiffness of the aorta. Student's t-test was performed to determine significant difference in stiffness measurements between normotensives and hypertensives. RESULTS: The normotensive group demonstrated a mean abdominal aortic stiffness of 3.7 +/- 0.8 kPa, while the controlled-hypertensive demonstrated a mean abdominal aortic stiffness of 9.3 +/- 1.9 kPa. MRE effective stiffness of abdominal aorta in hypertensives was significantly greater than that of normotensives with p = 0.02. CONCLUSION: Feasibility of in vivo aortic MRE is demonstrated. Hypertensives have significantly higher aortic stiffness assessed through MRE than normotensives. PMID- 22045618 TI - Local delivery of antimicrobial peptides using self-organized TiO2 nanotube arrays for peri-implant infections. AB - Peri-implant infections have been reported as one of the major complications that lead to the failure of orthopedic implants. An ideal solution to the peri-implant infection is to locally deliver antimicrobial agents through the implant surface. The rising problem of infections caused by multiple antibiotic-resistant bacteria makes traditional antibiotics less desirable for the prevention of peri-implant infections. One of the promising alternatives is the family of antimicrobial peptides (AMPs). In this study, we report the local delivery of AMPs through the nanotubular structure processed on titanium surface. Self-organized and vertically oriented TiO2 nanotubes, about 80 nm in diameter and 7 MUm thick, were prepared by the anodization technique. HHC-36 (KRWWKWWRR), one of the most potent broad-spectrum AMPs, was loaded onto the TiO2 nanotubes via a simple vacuum assisted physical adsorption method. Antimicrobial activity testing against Gram positive bacterium, Staphylococcus aureus, demonstrated that this AMP-loaded nanotubular surface could effectively kill the bacteria (~ 99.9% killing) and reduce the total bacterial number adhered to the surface after 4 h of culture. In vitro AMP elution from the nanotubes was investigated using liquid chromatography mass spectrometry (LC-MS). The release profiles strongly depended on the crystallinity of the TiO2 nanotubes. Anatase TiO2 nanotubes released significantly higher amounts of AMP than amorphous nanotubes during the initial burst release stage. Both followed almost the same slow release profile from 4 h up to 7 days. Despite the differences in release kinetics, no significant difference was observed between these two groups in bactericidal efficiency. PMID- 22045619 TI - Comparison of doxorubicin and weekly paclitaxel efficacy in metastatic angiosarcomas. AB - BACKGROUND: Data regarding the role of anthracyclines and taxanes as first-line treatments of metastatic angiosarcoma are limited. METHODS: Records of 117 metastatic angiosarcoma patients who were treated with either doxorubicin or weekly paclitaxel were reviewed. RESULTS: Seventy-five patients (64%) were treated with weekly paclitaxel and 42 (36%) with single-agent doxorubicin. Patients in the weekly paclitaxel group were older and more frequently had angiosarcomas arising from the skin. In the doxorubicin group, 34 patients were evaluable for response: 2 (6%) had complete response, 8 (23.5%) had partial response, 10 (29.5%) had stable disease, and 14 (41%) had progressive disease. In the weekly paclitaxel group, 68 patients were evaluable for response: 9 (13%) had complete response, 27 (40%) had partial response, 20 (29.5%) had stable disease, and 12 (17.5%) had progressive disease. Objective responses to weekly paclitaxel were more frequent in cutaneous angiosarcomas, whereas tumor location did not impact response to doxorubicin. Median progression-free survival (PFS) was 4.9 months (95% confidence interval [95% CI], 3.9-6.0 months). Median overall survival (OS) was 8.5 months (95% CI, 6.4-10.7 months). On multivariate analysis, ECOG performance status (PS) was the sole independent factor associated with PFS and OS. CONCLUSIONS: First-line single-agent doxorubicin and weekly paclitaxel seem to have similar efficacy in metastatic angiosarcomas. Cutaneous angiosarcomas respond favorably to weekly paclitaxel. Best supportive care should be considered in patients with poor PS. PMID- 22045620 TI - Cdc20 control of cell fate during prolonged mitotic arrest: do Cdc20 protein levels affect cell fate in response to antimitotic compounds? AB - The fate of cells arrested in mitosis by antimitotic compounds is complex but is influenced by competition between pathways promoting cell death and pathways promoting mitotic exit. As components of both of these pathways are regulated by Cdc20-dependent degradation, I hypothesize that variations in Cdc20 protein levels, rather than mutations in checkpoint genes, could affect cell fate during prolonged mitotic arrest. This hypothesis is supported by experiments where manipulation of Cdc20 levels affects the response to antimitotic compounds. The observed differences in Cdc20 levels between cell lines likely reflects differences in the rate of synthesis or degradation of the protein; therefore, understanding these pathways at a molecular level could pave the way for modulating the activity of Cdc20, in turn presenting novel therapeutic possibilities. PMID- 22045621 TI - Beyond petrochemicals: the renewable chemicals industry. PMID- 22045622 TI - Angiomatoid fibrous histiocytoma a series of five cytologic cases with literature review and emphasis on diagnostic pitfalls. AB - Angiomatoid fibrous histiocytoma (AFH) is an uncommon and mostly indolent soft tissue neoplasm, which usually occurs in the subcutaneous tissue of the extremities in children and young adults. Although the histologic features of AFH are well established, reports of its cytomorphology are very limited. This report characterizes the cytomorphologic features of five cases of AFH, with correlation to clinical, histology, and cytogenetic findings. Smears of fine needle aspiration (FNA; four cases) and intraoperative scrape (one case) were reviewed from five patients with a histologically confirmed diagnosis of AFH. A review of six previously reported AFH cases with cytomorphology was also performed. The tumor presented as a cystic, deep dermal mass in three pediatric cases and as a solid, deeply seated mass in two adults. The cytomorphologic features are mostly nondistinctive and include cellular smears with ovoid to spindled histiocytoid cells that may be isolated or in clusters. Some of these cells are atypical and others contain hemosiderin. Large cellular clusters with a capillary structure and a whorled arrangement of tumor cells can be appreciated in some cases. There is always a bloody background, but a lymphoplasmacytic infiltrate is uncommon. The presences of EWSR1 rearrangement in one case and three copies of FUS gene in another case were detected by fluorescence in situ hybridization. Diagnosing AFH by FNA cytology alone can be challenging because of its rarity and usually nonspecific cytologic findings. Clinical correlation and ancillary studies are essential to reach a specific diagnosis of AFH in small needle biopsies. PMID- 22045623 TI - Quantifying hemodynamic refractory bold effects in normal subjects at the single subject level using an inverse logit fitting procedure. AB - PURPOSE: To evaluate whether hemodynamic refractory effects provoked by repeated visual stimulation can be detected and quantified at the single-subject level using a recently described hemodynamic response function (HRF) fitting algorithm. MATERIALS AND METHODS: Hemodynamic refractory effects were induced with an easily applicable functional MRI (fMRI) paradigm. A fitting method with inverse logit (IL) functions was applied to quantify net HRFs at the single-subject level with three interstimulus intervals (ISI; 1, 2, and 6 s). The model yielded amplitude, latencies, and width for each HRF. RESULTS: HRF fitting was possible in 44 of 51 healthy volunteers, with excellent goodness-of-fit (R(2) = 0.9745 +/- 0.0241). Refractory effects were most pronounced for the 1-s ISI (P < 0.001) and had nearly disappeared for the 6-s ISI. CONCLUSION: Quantifying refractory effects in individuals was possible in 86.3% of normal subjects using the IL fitting algorithm. This setup may be suitable to explore such effects in individual patients. PMID- 22045624 TI - The effect of a bioactive tissue-engineered sling in a rat of stress incontinence model. AB - In this study, we attempt to examine the feasibility of the bioactive tissue engineered sling by using muscle precursor cells (MPCs)-seeded Poly(epsilon caprolactone) (PCL) nanofiber sheet in a rat model of stress urinary incontinence (SUI). In vitro, MPCs were cultured on a PCL nanofiber sheet for one week, where the MPCs-seeded PCL nanofiber sheet showed constant twitching contraction by electrical field stimulation in an organ bath. In vivo, MPCs-seeded PCL nanofiber sheet was placed under the female rat's urethra after pudendal nerve denervation (animal model of SUI). The leak point pressure (LPP) was evaluated with the vertical tilt table after the operation for four weeks. The resulting LPP of MPCs seeded PCL nanofiber sheet group was observed to be significantly higher than the denervation-only group's. Furthermore, PKH-26-labeled MPCs were observed under the urethral sphincter by immunohistochemistry. These results indicated that, the MPCs-seeded PCL nanofiber sheet have not only provided support for the deficient sphincter, but also actively improved the sphincter's function overall. In conclusion, this bioactive tissue-engineered sling could be used as an ideal material for the treatment of SUI. PMID- 22045625 TI - Out-of-hospital cardiac arrest: recent advances in resuscitation and effects on outcome. AB - Successful treatment of out-of-hospital cardiac arrest remains an unmet health need. Key elements of treatment comprise early recognition of cardiac arrest, prompt and effective cardiopulmonary resuscitation (CPR), effective defibrillation strategies and organised post-resuscitation care. The initiation of bystander CPR followed by a prompt emergency response that delivers high quality CPR is critical to outcomes. The integration of additional tasks such as defibrillation, airway management, vascular access and drug administration should avoid interruptions in chest compressions. Evidence for the routine use of CPR prompt/feedback devices, mechanical chest compression devices and pharmacological therapy is limited. PMID- 22045626 TI - Redox bifurcations: mechanisms and importance to life now, and at its origin: a widespread means of energy conversion in biology unfolds.... PMID- 22045628 TI - Palmitoyl-DL-carnitine is a multitarget inhibitor of Pseudomonas aeruginosa biofilm development. AB - Bacteria growing in biofilms are often in metabolic and physiological states that do not respond well to antibiotics, and thus, are major contributors to chronic diseases. Biofilm inhibitors, therefore, have the potential to be used alone or as adjuvants to conventional antibiotic therapies. Here, we screened a chemically diverse collection of protein kinase inhibitors for molecules that perturb biofilm development. Among the inhibitory molecules identified, palmitoyl-DL carnitine (pDLC) impaired Pseudomonas aeruginosa and Escherichia coli biofilm formation in a dose-dependent manner. The pDLC affected multiple pathways implicated in P. aeruginosa biofilm development; it stimulated motility, inhibited activity of the Las quorum sensing system, and overrode the biofilm promoting effects of subminimal inhibitory concentrations of aminoglycosides and high levels of the second messenger, cyclic-di-GMP. Palmitic acid, but not carnitine, inhibited biofilm formation but did not stimulate motility, suggesting that pDLC works through unique mechanisms. The ability to target multiple pathways involved in biofilm formation is desirable in an inhibitor, which makes pDLC an interesting lead for antibiofilm therapies. PMID- 22045627 TI - Involvement of the cGMP pathway in the osthole-facilitated glutamate release in rat hippocampal nerve endings. AB - Osthole, an active constituent isolated from Cnidium monnieri (L.) Cusson, has previously been shown to have the capacity to increase depolarization-evoked glutamate release in rat hippocampal nerve terminals. As cGMP-dependent signaling cascade has been found to modulate glutamate release at the presynaptic level, the aim of this study was to further examine the role of cGMP signaling pathway in the regulation of osthole on glutamate release in hippocampal synaptosomes. Results showed that osthole dose-dependently increased intrasynaptosomal cGMP levels. The elevation of cGMP levels by osthole was prevented by the phosphodiesterase 5 inhibitor sildenafil but was insensitive to the guanylyl cyclase inhibitor ODQ. In addition, osthole-induced facilitation of 4 aminopyridine (4-AP)-evoked glutamate release was completely prevented by the cGMP-dependent protein kinase (PKG) inhibitors, KT5823, and Rp-8-Br-PET-cGMPS. Direct activation of PKG with 8-Br-cGMP or 8-pCPT-cGMP also occluded the osthole mediated facilitation of 4-AP-evoked glutamate release. Furthermore, sildenafil exhibited a dose-dependent facilitation of 4-AP-evoked release of glutamate and occluded the effect of osthole on the 4-AP-evoked glutamate release. Collectively, our findings suggest that osthole-mediated facilitation of glutamate release involves the activation of cGMP/PKG-dependent pathway. PMID- 22045629 TI - Large platelet aggregates in endoscopic ultrasound-guided fine-needle aspiration of the pancreas and peripancreatic region: a clue for the diagnosis of intrapancreatic or accessory spleen. AB - Intrapancreatic and intraabdominal accessory spleens (IPIASs) are rarely encountered in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsies. However, as incidentally discovered IPIAS can mimic a benign or malignant pancreatic neoplasm on imaging studies, a definitive diagnosis made by EUS-FNA can avert an unnecessary surgical intervention or additional radiologic follow-up. We report five cases of intrapancreatic splenules and one case of accessory spleen (AS) in which a definitive diagnosis was made on EUS-FNA. Previously recognized FNA cytomorphologic features of splenic tissue, including ASs and splenosis, are endothelial cells and polymorphous lymphocytes admixed with neutrophils, eosinophils, plasma cells, histiocytes, and lymphoglandular bodies. We describe the additional finding of abundant large platelet aggregates as another distinguishing feature of splenic tissue on FNA. In all six cases, large platelet aggregates were identified along with polymorphous lymphoid cells, lymphoglandular bodies, loose aggregates of endothelial cells and scattered or aggregated bland spindle cells. A review of 10 consecutive cases of EUS-FNA sampled benign intraabdominal lymph nodes showed that the presence of large platelet aggregates, three-dimensional aggregates of lymphoid cells and of bland slender spindle cells and the absence of follicular germinal cell components (tingible body macrophages and lymphohistiocytic aggregates) are useful in differentiating IPIASs from reactive lymph nodes. Immunoperoxidase stains were useful to confirm a suspected IPIASs by showing CD31-positive acellular flocculent material, consistent with large platelet aggregates and a rich CD8 positive endothelial cell network between CD45-positive lymphoid cells and CD68 positive histiocytes in all six cases. PMID- 22045630 TI - Gadofluorine M enhanced MRI in experimental glioma: superior and persistent intracellular tumor enhancement compared with conventional MRI. AB - PURPOSE: To compare conventional magnetic resonance imaging (MRI) techniques (T2 w and Gadolinium-DTPA-enhanced T1-w images) and Gadofluorine-M (GfM), a novel contrast agent in MRI, in murine gliomas. MATERIALS AND METHODS: Growth monitoring of murine gliomas (induced in mice) was performed on a 2.3 Tesla Bruker Biospec MRI unit. First all animals were investigated with conventional MRI techniques. In group I GfM was applied at an early stage of disease, in group II at a later stage. After injection of GfM follow-up MRI was performed without further injection of contrast agent. On MR images tumor size and signal intensities were assessed. Animals were killed for histological evaluation. RESULTS: In both groups GfM delineated tumor extents larger and more precisely than conventional MRI techniques. The difference between GfM and conventional MRI techniques reached level of significance at both tumor stages. Follow-up MRI after singular injection of GfM showed persistence of GfM in tumor tissue. On tissue sections GfM-enhancing areas corresponded closely to vital tumor tissue. GfM showed a mainly intracellular accumulation. CONCLUSION: Application of GfM resulted in superior delineation of experimental glioma compared with conventional MRI techniques. Thus, GfM bears a high potential in clinical application. PMID- 22045631 TI - In vitro and in vivo evaluations on osteogenesis and biodegradability of a beta tricalcium phosphate coated magnesium alloy. AB - Magnesium (Mg) alloys have been demonstrated to be potential orthopedic implants due to their biodegradability in vivo. To enhance its corrosion resistance and improve its osteogenesis, beta-tricalcium phosphate (beta-TCP) was coated on a Mg alloy (Mg-3AI-1Zn) by phosphating process. In vitro, the human osteosarcoma cell line (SaOS-2) showed significantly good adherence and proliferation on the surface of the beta-TCP coated Mg alloy after 24-h incubation. The growth factor bone morphogenetic protein 2 (BMP-2) was highly expressed in SaOS-2 cultured with the beta-TCP coated Mg alloy by Western blot analysis (p < 0.05). In vivo, the newborn bone at the implant/bone interface was formed at week 1 and matured at week 4 postimplantation. Villous tissue was found at the implant/bone interface at week 12 postimplantation. The contents of phosphorus and calcium on the surface of the beta-TCP coated Mg alloy were decreased at week 4 and week 12 postimplantation, respectively. Immunohistochemical analysis of the experiment results demonstrated that the beta-TCP coated Mg alloy implants provided a high BMP-2 expression during the first 4 weeks postimplantation. Compared with the naked Mg alloy which was degraded for 33% in vivo, only 17% of the beta-TCP coated Mg alloy was degraded at week 12 postimplantation (p < 0.05). The in vitro cell tests showed that the beta-TCP coating provided the Mg alloy with a significantly better surface cytocompatibility, and in vivo results also confirmed that the beta-TCP coating exhibited greatly improved osteoconductivity and osteogenesis in the early 12 weeks postoperation period. Moreover, in vivo experiment demonstrated that the beta-TCP coating layer could slow down the degradation of the naked Mg alloy at the early stage of implantation. PMID- 22045632 TI - Dr. Sanger, meet Mr. Moore: next-generation sequencing is driving new questions and new modes of research. PMID- 22045633 TI - Determination of hemin-binding characteristics of proteins by a combinatorial peptide library approach. AB - Studies of the binding of heme/hemin to proteins or peptides have recently intensified as it became evident that heme serves not only as a prosthetic group, but also as a regulator and effector molecule interacting with transmembrane and cytoplasmic proteins. The iron-ion-containing heme group can associate with these proteins in different ways, with the amino acids Cys, His, and Tyr allowing individual modes of binding. Strong coordinate-covalent binding, such as in cytochrome c, is known, and reversible attachment is also discussed. Ligands for both types of binding have been reported independently, though sometimes with different affinities for similar sequences. We applied a combinatorial approach using the library (X)(4) (C/H/Y)(X)(4) to characterize peptide ligands with considerable hemin binding capacities. Some of the library-selected peptides were comparable in terms of hemin association independently of whether or not a cysteine residue was present in the sequence. Indeed, a preference for His-based (~39 %) and Tyr-based (~40 %) sequences over Cys-based ones (~21 %) was detected. The binding affinities for the library-selected peptides, as determined by UV/Vis spectroscopy, were in the nanomolar range. Moreover, selected representatives efficiently competed for hemin binding with the human BK channel hSlo1, which is known to be regulated by heme through binding to its heme-binding domain. PMID- 22045634 TI - Water-soluble distyrylbenzenes: one core with two sensory responses--turn-on and ratiometric. AB - The synthesis of four water-soluble distyrylbenzenes (compounds 1-4) is reported. Their acidochromicity in aqueous media was investigated. Blue shifts and increases in the quantum yields were observed as a general response. The pH dependent photophysics of 1b-3b in water reveal unexpected protonation sequences upon titration: compound 1b is green-yellow fluorescent at high pH (10) but becomes very weakly fluorescent between pH 5 and pH 3, whereas below pH 2 strong blue fluorescence is observed. This behavior can be explained in terms of the interplay in the protonation of aniline and of the carboxylate groups. In compound 4, a higher basicity of the amino group is observed and ratiometric fluorescence change takes place upon protonation or on reaction with zinc salts in water. Compound 4 can therefore act as a weak ratiometric zinc ligand in water, even though it has only a dimethylamino unit as a binding motif. PMID- 22045635 TI - Abundant amyloid deposits in endoscopic ultrasound-guided fine-needle aspiration biopsy of pancreatic endocrine neoplasms. PMID- 22045638 TI - Are tumor cells protected from some anti-cancer drugs by elevated APC/C activity? (comment on DOI: 10.1002/bies.201100094). PMID- 22045639 TI - As time goes by. PMID- 22045640 TI - Choosing a cell sorting option to study the fate of bystander cells: FACS or MACS? PMID- 22045636 TI - Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias. AB - In 1994, the field of bone biology was significantly advanced by the discovery that activating mutations in the fibroblast growth factor receptor 3 (FGFR3) receptor tyrosine kinase (TK) account for the common genetic form of dwarfism in humans, achondroplasia (ACH). Other conditions soon followed, with the list of human disorders caused by FGFR3 mutations now reaching at least 10. An array of vastly different diagnoses is caused by similar mutations in FGFR3, including syndromes affecting skeletal development (hypochondroplasia [HCH], ACH, thanatophoric dysplasia [TD]), skin (epidermal nevi, seborrhaeic keratosis, acanthosis nigricans), and cancer (multiple myeloma [MM], prostate and bladder carcinoma, seminoma). Despite many years of research, several aspects of FGFR3 function in disease remain obscure or controversial. As FGFR3-related skeletal dysplasias are caused by growth attenuation of the cartilage, chondrocytes appear to be unique in their response to FGFR3 activation. However, the reasons why FGFR3 inhibits chondrocyte growth while causing excessive cellular proliferation in cancer are not clear. Likewise, the full spectrum of molecular events by which FGFR3 mediates its signaling is just beginning to emerge. This article describes the challenging journey to unravel the mechanisms of FGFR3 function in skeletal dysplasias, the extraordinary cellular manifestations of FGFR3 signaling in chondrocytes, and finally, the progress toward therapy for ACH and cancer. PMID- 22045641 TI - Cell cycle dependent TN-C promoter activity determined by live cell imaging. AB - The extracellular matrix protein tenascin-C plays a critical role in development, wound healing, and cancer progression, but how it is controlled and how it exerts its physiological responses remain unclear. By quantifying the behavior of live cells with phase contrast and fluorescence microscopy, the dynamic regulation of TN-C promoter activity is examined. We employ an NIH 3T3 cell line stably transfected with the TN-C promoter ligated to the gene sequence for destabilized green fluorescent protein (GFP). Fully automated image analysis routines, validated by comparison with data derived from manual segmentation and tracking of single cells, are used to quantify changes in the cellular GFP in hundreds of individual cells throughout their cell cycle during live cell imaging experiments lasting 62 h. We find that individual cells vary substantially in their expression patterns over the cell cycle, but that on average TN-C promoter activity increases during the last 40% of the cell cycle. We also find that the increase in promoter activity is proportional to the activity earlier in the cell cycle. This work illustrates the application of live cell microscopy and automated image analysis of a promoter-driven GFP reporter cell line to identify subtle gene regulatory mechanisms that are difficult to uncover using population averaged measurements. PMID- 22045642 TI - A high throughput, interactive imaging, bright-field wound healing assay. AB - The wound healing assay is a commonly used technique to measure cell motility and migration. Traditional methods of performing the wound healing assay suffer from low throughput and a lack of quantitative data analysis. We have developed a new method to perform a high-throughput wound healing assay that produces quantitative data using the LEAPTM instrument. The LEAPTM instrument is used to create reproducible wounds in each well of a 96-well plate by laser ablation. The LEAPTM then records bright field images of each well at several time points. A custom texture segmentation algorithm is used to determine the wound area of each well at each time point. This texture segmentation analysis can provide faster and more accurate image analysis than traditional methods. Experimental results show that reproducible wounds are created by laser ablation with a wound area that varies by less than 10%. This method was tested by confirming that neuregulin-2beta increases the rate of wound healing by MCF7 cells in a dose dependent manner. This automated wound healing assay has greatly improved the speed and accuracy, making it a suitable high-throughput method for drug screening. PMID- 22045643 TI - A miniature Couette to generate shear for flow cytometry: studying real-time modulation of intracellular calcium in monocytic cells. AB - Extracellular hydrodynamic forces may be transmitted to the interior of cells through the alteration of integrin conformation and affinity. Integrin activation regulates leukocyte recruitment, cell activation, and transmigration. The cellular and molecular mechanisms for integrin activation are not precisely known, although intracellular calcium signaling is involved. Flow cytometry offers a versatile way to study intracellular calcium signaling in real-time. We report a novel method to generate defined shear by using a miniature Couette. Testing involved measuring shear-induced intracellular calcium signals of human monoblastoid U937 cells in suspension. The Couette was connected externally to a flow cytometer and pressurized at 6 PSI (4.1 N/m(2) ). Cells were subjected to a well-defined shear between 0 and 1,000 s(-1) and delivered continuously within 10 s to a FACScan at 1 MUl/s. Intracellular calcium levels and the percentage of cells activated increased as shear increased in duration and intensity. PMID- 22045646 TI - Preferential affinity of the components of liquid mixtures at a rigid non-polar surface: enthalpic and entropic driving forces. AB - The modulation of the properties of lipid membranes by polyhydroxylated cosolutes such as sugars is a phenomenon of considerable biological, technological and medicinal relevance. A few years ago, we proposed the sugar-like mechanism- binding driven by the release of water molecules--as an attempt to rationalize the preferential affinity of carbohydrate molecules compared to water molecules for the surface of lipid bilayers, which is presumably related to the bioprotective action of these compounds. The goal herein is to gain a better understanding of the driving force underlying this mechanism, in terms of specific interactions or effects, as well as in terms of the energy-entropy partitioning. This is done in the simplest possible context of an apolar rigid wall model representing the membrane, and mixtures of closely related and possibly artificial species in solution, namely monomers or dimers of Lennard Jones particles, water with physical or reduced charges, and hydroxymethyl groups. The results indicate that although the sugar-like mechanism seems phenomenologically reasonable, the main driving force underlying this mechanism is not the entropy gain upon releasing water molecules into the bulk, as originally suggested, but rather the hydrophobic effect. Note that the latter effect is a generic concept and may in principle involve both a solvent release and an interaction component, depending on the solute considered. PMID- 22045647 TI - A place for assaying serum apolipoprotein AI and B? PMID- 22045648 TI - The '70% claim': what is the evidence base? PMID- 22045649 TI - Assessment of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status in the fine needle aspirates of metastatic breast carcinomas. AB - The assessment of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2) status in the fine needle aspirates of metastatic breast carcinomas has prognostic and therapeutic implications. In this study, expression of ER, PR, and HER2 was assessed by immunohistochemical study in 70 cases of metastatic breast carcinomas and HER2 gene amplification was further evaluated by fluorescence in situ hybridization (FISH) in 38 (54%) cases. Positive expression of ER and PR was seen in 42 (60%) and 16 (23%) cases of metastatic breast carcinomas, respectively. HER2 immunoreactivity was scored as 0/1+ in 39 (56%), 2+ in 10 (14%), and 3+ in 21 (30%) cases. HER2 gene amplification was seen in 20% of HER2 2+ and 64% of HER2 3+ cases. ER, PR, and HER2 status in primary breast cancers were available to comparison in 31 cases (44%). The concordance rates between metastatic and primary breast carcinomas were 81% for ER, 65% for PR and 71% for HER2. Our study demonstrates that ER, PR, and HER2 status can be assessed in the fine needle aspirates of metastatic breast carcinomas and ER has a higher concordance rate between metastatic and primary breast carcinomas than PR and HER2. The addition of HER2 gene amplification FISH test helps in accurate assessment of HER2 status in metastatic breast carcinomas. PMID- 22045650 TI - The aqueduct of Sylvius: a sonographic landmark for neural tube defects in the first trimester. AB - OBJECTIVES: To describe a new first-trimester sonographic landmark, posterior displacement of the midbrain and aqueduct of Sylvius, which may be useful in early screening for neural tube defects. METHODS: This was a prospective study of 457 normal fetuses at 11 + 0 to 13 + 6 weeks' gestation. We measured the distance from the posterior border of the aqueduct of Sylvius to the anterior border of the occiput (AOS-to-occiput distance) in the axial plane and created a reference range. In the nine fetuses with abnormal midbrain position identified in the first trimester and with neural tube defect subsequently confirmed, we analyzed ultrasound images to determine the position of the aqueduct of Sylvius. RESULTS: The lower limit of normal AOS-to-occiput distance (mean minus 2 SD) ranged from 1.7 mm at a crown-rump length (CRL) of 45 mm to 3.7 mm at a CRL of 84 mm. In the nine cases with abnormal position of the midbrain and confirmed neural tube defect, juxtaposition of the midbrain to the occiput was the clue to diagnosis of the spinal abnormality. In all nine cases, the AOS-to-occiput distance was below the established normal range. CONCLUSIONS: Examination of the midbrain in an axial plane may prove a reliable marker for the first-trimester diagnosis of neural tube defects. In contrast to recently reported subtle changes in the mid sagittal view of the posterior cranial fossa, axial imaging of the midbrain reveals striking displacement of this structure, with virtual juxtaposition to the occiput, in fetuses with confirmed open spina bifida. This anatomical distortion of the midbrain can be quantified by measurement of the AOS-to-occiput distance. PMID- 22045651 TI - Novel comprehensive diagnostic strategy in Pitt-Hopkins syndrome: clinical score and further delineation of the TCF4 mutational spectrum. AB - Pitt-Hopkins syndrome (PTHS), characterized by severe intellectual disability and typical facial gestalt, is part of the clinical spectrum of Rett-like syndromes. TCF4, encoding a basic helix-loop-helix (bHLH) transcription factor, was identified as the disease-causing gene with de novo molecular defects. While PTHS appears to be a recognizable clinical entity, it seems to remain underdiagnosed, especially when facial gestalt is less typical. With the aim to facilitate the diagnosis of PTHS and to increase its rate and specificity, we have investigated 33 novel patients and defined a Clinical Diagnosis Score. Analysis of 112 individuals (79 previously reported and 33 novel patients) allowed us to delineate the TCF4 mutational spectrum, with 40% point mutations, 30% small deletions/insertions, and 30% deletions. Most of these were private mutations and generated premature stop codons. Missense mutations were localized in the bHLH domain, which is a mutational hotspot. No obvious difference was observed between patients harboring truncating, missense mutations, or deletions, further supporting TCF4 haploinsufficiency as the molecular mechanism underlying PTHS. In this study, we have summarized the current knowledge of TCF4 molecular pathology, reported all the mutations in the TCF4 database (http://www.LOVD.nl/TCF4), and present a novel and comprehensive diagnostic strategy for PTHS. PMID- 22045652 TI - Receptor tyrosine kinase pathway analysis sheds light on similarities between clear-cell sarcoma and metastatic melanoma. AB - To highlight possible similarities and differences in receptor tyrosine kinase (RTK) and downstream signalling activation profiles between clear-cell sarcomas (CCS) and metastatic melanomas (MM), frozen, and paired-matched fixed samples of six CCS with EWSR1 rearrangement (EWSR1+), five CCS without EWSR1 rearrangement (EWSR1-), and seven MM were investigated by means of biochemical, immunohistochemical, FISH, molecular analyses, and immunofluorescence confocal microscopy. Fixed samples of a further 10 CCS and 14 MM were investigated by means of sequencing for BRAF, NRAS, and KRAS mutations and FISH analyses for the gain of chromosomes 22 and 8. RTK analysis of all CCS/MM samples showed activation of short-form (sf) recepteur d'origine nantais (RON) RTK and of PDGFRB, MET, and HER3. Analysis of downstream signaling revealed consistent phosphorylation patterns of PI3K/AKT, RSK, and the mTOR targets S6 and 4EBP1. Analysis of frozen and fixed material from 21 CCS and 21 MM showed the presence of the V600E BRAF mutation in 2/12 EWSR1+ and 3/9 EWSR1- CCS and 9/21 MM and demonstrated a significant (P < 0.001) correlation between the gain of chromosomes 22 and 8 and EWSR1- CCS. Our results show that BRAF mutation can also be present in CCS and support the proposed aberration of chromosomes 22 and 8 as a possibly useful nonrandom hallmark of EWSR1- CCS. Besides, they broaden the spectrum of the similarities of RTK pathway activation between CCS and MM, thus suggesting that new drugs found to be active in melanoma and RON inhibitors could have a role in CCS treatment. (c) 2011 Wiley Periodicals, Inc. PMID- 22045654 TI - Curcumin attenuates diabetic nephropathy by inhibiting PKC-alpha and PKC-beta1 activity in streptozotocin-induced type I diabetic rats. AB - SCOPE: We hypothesized that curcumin, a potent anti-oxidant, might be beneficial in ameliorating the development of diabetic nephropathy through inhibition of PKC alpha and PKC-beta1 activity-ERK1/2 pathway. METHODS AND RESULTS: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg) in rats. Three weeks after STZ injection, rats were divided into three groups, namely, normal, diabetic and diabetic treated with curcumin at 100 mg/kg/day, p.o., for 8 wk. At 11 wk after STZ injection, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, increased blood urea nitrogen (BUN) and proteinuria, marked increases in lipid peroxidation, NOX4 and p67phox and decrease in anti-oxidant enzyme. All of these abnormalities were significantly reversed by curcumin. Furthermore, the high-glucose-induced PKC alpha and PKC-beta1 activities and phosphorylated ERK1/2 was significantly diminished by curcumin. Curcumin also attenuated the expression of TGF-beta1, CTGF, osteopontin, p300 and ECM proteins such as fibronectin and type IV collagen. The high-glucose-induced expression of VEGF and its receptor VEGF receptor II (flk-1) was also ameliorated by curcumin. CONCLUSION: These results prove that curcumin produces dual blockade of both PKC-alpha and PKC-beta1 activities, which suggests that curcumin is a potential adjuvant therapy for the prevention and treatment of diabetic nephropathy. PMID- 22045655 TI - Anti-proliferative effect of curcumin on melanoma cells is mediated by PDE1A inhibition that regulates the epigenetic integrator UHRF1. AB - SCOPE: Curcumin inhibits proliferation of many cancer cells. Cyclic nucleotide phosphodiesterases (PDEs), by hydrolyzing intracellular cyclic adenosine-3',5' monophosphate (cAMP) and/or cyclic guanosine-3',5'-monophosphate (cGMP), play a pivotal role in signalling pathways involved in cell proliferation. Therefore, this study investigated PDE1-5 participations in the anti-proliferative properties of curcumin in B16F10 murine melanoma cells. METHODS AND RESULTS: We report that curcumin inhibits PDE1-5 activities (IC(50) ?10(-5) M), indicating that curcumin acts as a non-selective PDE inhibitor. In melanoma cells, PDE4 and PDE1 represent the major cAMP-PDEs and cGMP-PDEs activities, respectively. Curcumin treatment decreased PDE1 and PDE4 activities and dose dependently increased intracellular cGMP levels, whereas cAMP levels were unchanged. Curcumin inhibited cell proliferation and cell cycle progression by accumulating cells in the S- and G2/M-phases with enhanced expressions of cyclin-dependent kinase inhibitors. In contrast, expressions of PDE1A, cyclin A and the epigenetic integrator ubiquitin-like containing PHD and Ring Finger domains 1 (UHRF1) and DNA methyltransferase 1 (DNMT1) were decreased by curcumin. Interestingly, PDE1A overexpression increased UHRF1 and DNMT1 expressions and rescued the B16F10 cells from curcumin anti-proliferative effects. Nimodipine, a PDE1 inhibitor, mimicked the curcumin effects. CONCLUSION: Curcumin exerts its anti-cancer property by targeting PDE1 that inhibits melanoma cell proliferation via UHRF1, DNMT1, cyclin A, p21 and p27 regulations. This suggests that natural PDE1 inhibitors present in food might be effective in preventing cancer. PMID- 22045656 TI - Allergenic and immunogenic potential of cow's milk beta-lactoglobulin and caseins evidenced without adjuvant in germ-free mice. AB - SCOPE: In most animal models of allergy, the development of an IgE response requires the use of an adjuvant. Germ-free (GF) mice exhibit Th2-polarized antibody responses combined with defective immunosuppressive mechanisms. The sensitizing potential of milk proteins was investigated in GF mice in the absence of adjuvant. METHODS AND RESULTS: beta-lactoglobulin (BLG) and whole casein (CAS) allergenicity was evaluated by means of intraperitoneal injections without adjuvant. Injections of BLG induced significant IgE and IgG1 responses in GF mice, while CAS injections provoked the production of IgG1 toward kappa- and alphaS1-caseins. No significant antibody response was evidenced in conventional (CV) mice. After in vitro BLG-reactivation, IL-4, IL-5, IL-13 and IFN-gamma productions by splenocytes were higher in GF mice than in CV mice. Heat-treatment decreased BLG allergenicity as indicated by the absence of IgE production in GF mice. However, heat-treatment increased protein immunogenicity and led to the production of anti-BLG and anti-kappa-casein IgG1 in both GF and CV mice. This correlated with enhanced productions of IL-4, IL-5 and IL-13 in BLG-reactivated splenocytes from CV mice. CONCLUSION: Gut colonization by commensal bacteria appeared then to significantly reduce the susceptibility of mice toward the intrinsic allergenic and immunogenic potential of milk proteins. PMID- 22045657 TI - Formation of dopamine quinone-DNA adducts and their potential role in the etiology of Parkinson's disease. AB - The neurotransmitter dopamine is oxidized to its quinone (DA-Q), which at neutral pH undergoes intramolecular cyclization by 1,4-Michael addition, followed by oxidation to form leukochrome, then aminochrome, and finally neuromelanin. At lower pH, the amino group of DA is partially protonated, allowing the competitive intermolecular 1,4-Michael addition with nucleophiles in DNA to form the depurinating adducts, DA-6-N3Ade and DA-6-N7Gua. Catechol estrogen-3,4-quinones react by 1,4-Michael addition to form the depurinating 4 hydroxyestrone(estradiol)-1-N3Ade [4-OHE1(E2)-1-N3Ade] and 4-OHE1(E2)-1-N7Gua adducts, which are implicated in the initiation of breast and other human cancers. The effect of pH was studied by reacting tyrosinase-activated DA with DNA and measuring the formation of depurinating adducts. The most adducts were formed at pH 4, 5, and 6, and their level was nominal at pH 7 and 8. The N3Ade adduct depurinated instantaneously, but N7Gua had a half-life of 3 H. The slow loss of the N7Gua adduct is analogous to that observed in previous studies of natural and synthetic estrogens. The antioxidants N-acetylcysteine and resveratrol efficiently blocked formation of the DA-DNA adducts. Thus, slightly acidic conditions render competitive the reaction of DA-Q with DNA to form depurinating adducts. We hypothesize that formation of these adducts could lead to mutations that initiate Parkinson's disease. If so, use of N-acetylcysteine and resveratrol as dietary supplements may prevent initiation of this disease. PMID- 22045658 TI - Cytologic features of subependymoma with extensive microcystic transformation. PMID- 22045659 TI - Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis. AB - MicroRNAs (miRNAs) are studied as key regulators of gene expression involved in different diseases. Several single nucleotide polymorphisms (SNPs) in miRNA genes or target sites (miRNA-related SNPs) have been proved to be associated with human diseases by affecting the miRNA-mediated regulatory function. To systematically analyze miRNA-related SNPs and their effects, we performed a genome-wide scan for SNPs in human pre-miRNAs, miRNA flanking regions, target sites, and designed a pipeline to predict the effects of them on miRNA-target interaction. As a result, we identified 48 SNPs in human miRNA seed regions and thousands of SNPs in 3' untranslated regions with the potential to either disturb or create miRNA-target interactions. Furthermore, we experimentally confirmed seven loss-of-function SNPs and one gain-of-function SNP by luciferase assay. This is the first case of experimental validation of an SNP in an miRNA creating a novel miRNA target binding. All useful data were complied into miRNASNP, a user-friendly free online database (http://www.bioguo.org/miRNASNP/). These data will be a useful resource for studying miRNA function, identifying disease-associated miRNAs, and further personalized medicine. PMID- 22045660 TI - An irradiation-altered bone marrow microenvironment impacts anabolic actions of PTH. AB - PTH stimulates bone formation and increases hematopoietic stem cells through mechanisms as yet uncertain. The purpose of this study was to identify mechanisms by which PTH links actions on cells of hematopoietic origin with osteoblast mediated bone formation. C57B6 mice (10 d) were nonlethally irradiated and then administered PTH for 5-20 d. Irradiation reduced bone marrow cellularity with retention of cells lining trabeculae. PTH anabolic activity was greater in irradiated vs. nonirradiated mice, which could not be accounted for by altered osteoblasts directly or osteoclasts but instead via an altered bone marrow microenvironment. Irradiation increased fibroblast growth factor 2, TGFbeta, and IL-6 mRNA levels in the bone marrow in vivo. Irradiation decreased B220 cell numbers, whereas the percent of Lin(-)Sca-1(+)c-kit(+) (LSK), CD11b(+), CD68(+), CD41(+), Lin(-)CD29(+)Sca-1(+) cells, and proliferating CD45(-)Nestin(+) cells was increased. Megakaryocyte numbers were reduced with irradiation and located more closely to trabecular surfaces with irradiation and PTH. Bone marrow TGFbeta was increased in irradiated PTH-treated mice, and inhibition of TGFbeta blocked the PTH augmentation of bone in irradiated mice. In conclusion, irradiation created a permissive environment for anabolic actions of PTH that was TGFbeta dependent but osteoclast independent and suggests that a nonosteoclast source of TGFbeta drives mesenchymal stem cell recruitment to support PTH anabolic actions. PMID- 22045662 TI - Fetal sex affects expression of renin-angiotensin system components in term human decidua. AB - The maternal decidua expresses the genes of the renin-angiotensin system (RAS). Human decidua was collected at term either before labor (i.e. cesarean delivery) or after spontaneous labor. The mRNA for prorenin (REN), prorenin receptor (ATP6AP2), angiotensinogen (AGT), angiotensin-converting enzymes 1 and 2 (ACE1 and ACE2), angiotensin II type 1 receptor (AGTR1), and angiotensin 1-7 receptor (MAS1) were measured by quantitative real-time RT-PCR. Decidual explants were cultured in duplicate for 24 and 48 h, and all RAS mRNA, and the secretion of prorenin, angiotensin II, and angiotensin 1-7 was measured using quantitative real-time RT-PCR, ELISA, and radioimmunoassay, respectively. In the decidua collected before labor, REN mRNA levels were higher if the fetus was female. In addition, REN, ATP6AP2, AGT, and MAS1 mRNA abundance was greater in decidual explants collected from women carrying a female fetus, as was prorenin protein. After 24 h, ACE1 mRNA was higher in the decidual explants from women with a male fetus, whereas after 48 h, both ACE1 and ACE2 mRNA was higher in decidual explants from women with a female fetus. Angiotensin II was present in all explants, but angiotensin 1-7 levels often registered below the lower limits of sensitivity for the assay. After labor, decidua, when compared with nonlaboring decidua, demonstrated lower REN expression when the fetus was female. Therefore, the maternal decidual RAS is regulated in a sex-specific manner, suggesting that it may function differently when the fetus is male than when it is female. PMID- 22045661 TI - Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone. AB - Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion in birds and mammals. To further understand its physiological roles in mammalian reproduction, we identified its precursor cDNA and endogenous mature peptides in the Siberian hamster brain. The Siberian hamster GnIH precursor cDNA encoded two RFamide-related peptide (RFRP) sequences. SPAPANKVPHSAANLPLRF-NH(2) (Siberian hamster RFRP-1) and TLSRVPSLPQRF-NH(2) (Siberian hamster RFRP-3) were confirmed as mature endogenous peptides by mass spectrometry from brain samples purified by immunoaffinity chromatography. GnIH mRNA expression was higher in long days (LD) compared with short days (SD). GnIH mRNA was also highly expressed in SD plus pinealectomized animals, whereas expression was suppressed by melatonin, a nocturnal pineal hormone, administration. GnIH-immunoreactive (-ir) neurons were localized to the dorsomedial region of the hypothalamus, and GnIH-ir fibers projected to hypothalamic and limbic structures. The density of GnIH-ir perikarya and fibers were higher in LD and SD plus pinealectomized hamsters than in LD plus melatonin or SD animals. The percentage of GnRH neurons receiving close appositions from GnIH-ir fiber terminals was also higher in LD than SD, and GnIH receptor was expressed in GnRH-ir neurons. Finally, central administration of hamster RFRP-1 or RFRP-3 inhibited LH release 5 and 30 min after administration in LD. In sharp contrast, both peptides stimulated LH release 30 min after administration in SD. These results suggest that GnIH peptides fine tune LH levels via its receptor expressed in GnRH-ir neurons in an opposing fashion across the seasons in Siberian hamsters. PMID- 22045663 TI - Spermatogonia differentiation requires retinoic acid receptor gamma. AB - Vitamin A is instrumental to mammalian reproduction. Its metabolite, retinoic acid (RA), acts in a hormone-like manner through binding to and activating three nuclear receptor isotypes, RA receptor (RAR)alpha (RARA), RARbeta, and RARgamma (RARG). Here, we show that 1) RARG is expressed by A aligned (A(al)) spermatogonia, as well as during the transition from A(al) to A(1) spermatogonia, which is known to require RA; and 2) ablation of Rarg, either in the whole mouse or specifically in spermatogonia, does not affect meiosis and spermiogenesis but impairs the A(al) to A(1) transition in the course of some of the seminiferous epithelium cycles. Upon ageing, this phenomenon yields seminiferous tubules containing only spermatogonia and Sertoli cells. Altogether, our findings indicate that RARG cell-autonomously transduces, in undifferentiated spermatogonia of adult testes, a RA signal critical for spermatogenesis. During the prepubertal spermatogenic wave, the loss of RARG function can however be compensated by RARA, as indicated by the normal timing of appearance of meiotic cells in Rarg-null testes. Accordingly, RARG- and RARA-selective agonists are both able to stimulate Stra8 expression in wild-type prepubertal testes. Interestingly, inactivation of Rarg does not impair expression of the spermatogonia differentiation markers Kit and Stra8, contrary to vitamin A deficiency. This latter observation supports the notion that the RA-signaling pathway previously shown to operate in Sertoli cells also participates in spermatogonia differentiation. PMID- 22045664 TI - Stretch and inflammatory cytokines drive myometrial chemokine expression via NF kappaB activation. AB - Both human preterm labor (PTL) and term labor are consistently associated with a chemokine-induced inflammatory infiltration of the myometrium. However, what regulates myometrial chemokine expression and whether the increase in expression precedes the onset of labor, and so may have a role in its causation, or occurs after, and is simply a consequence of labor, is uncertain. Therefore, we assessed 1) chemokine expression in nonlaboring and laboring myometrial samples obtained at and before term and 2) the factors that regulate myometrial chemokine expression. We found that term labor was characterized by an increase in CXCL8 and CCL2 in both upper and lower segments, whereas PTL was associated with a distinct pattern of chemokine expression, with increases in CCL5, CXCL5, and CCL20 in the lower segment myometrium only. Further, we found that chemokine expression in myometrial cell cultures was increased by stretch and inflammatory cytokines and reduced by prostglandins and oxytocin and that the primary mediator of stretch and cytokine effects was nuclear factor kappaB (NF-kappaB) and to a lesser extent MAPK. These data show that PTL appears to be associated with a distinct pattern of chemokine expression, that stretch and cytokines both drive myometrial chemokine expression primarily via activation of NF-kappaB. These data suggest that the modulation of NF-kappaB activity may be of potential benefit in the management of PTL. PMID- 22045665 TI - Enhanced fatty acid flux triggered by adiponectin overexpression. AB - Adiponectin overexpression in mice increases insulin sensitivity independent of adiposity. Here, we combined stable isotope infusion and in vivo measurements of lipid flux with transcriptomic analysis to characterize fatty acid metabolism in transgenic mice that overexpress adiponectin via the aP2-promoter (ADNTg). Compared with controls, fasted ADNTg mice demonstrated a 31% reduction in plasma free fatty acid concentrations (P = 0.008), a doubling of ketones (P = 0.028), and a 68% increase in free fatty acid turnover in plasma (15.1 +/- 1.5 vs. 25.3 +/- 6.8 mg/kg . min, P = 0.011). ADNTg mice had 2-fold more brown adipose tissue mass, and triglyceride synthesis and turnover were 5-fold greater in this organ (P = 0.046). Epididymal white adipose tissue was slightly reduced, possibly due to the approximately 1.5-fold increase in the expression of genes involved in oxidation (peroxisome proliferator-activated receptor alpha, peroxisome proliferator-activated receptor-gamma coactivator 1alpha, and uncoupling protein 3). In ADNTg liver, lipogenic gene expression was reduced, but there was an unexpected increase in the expression of retinoid pathway genes (hepatic retinol binding protein 1 and retinoic acid receptor beta and adipose Cyp26A1) and liver retinyl ester content (64% higher, P < 0.02). Combined, these data support a physiological link between adiponectin signaling and increased efficiency of triglyceride synthesis and hydrolysis, a process that can be controlled by retinoids. Interactions between adiponectin and retinoids may underlie adiponectin's effects on intermediary metabolism. PMID- 22045666 TI - PTEN genomic deletions that characterize aggressive prostate cancer originate close to segmental duplications. AB - Deletion of PTEN at 10q23.3 occurs in ~40% of human prostate cancers and is associated with aggressive metastatic potential, poor prognosis, and androgen independence. This high frequency of recurrent PTEN deletions in prostate cancer suggests there may be unusual genomic features close to this locus that facilitate DNA alteration at 10q23.3. To explore possible mechanisms for deletions in the PTEN region, a meta-analysis of 311 published human genome array datasets was conducted and determined that the minimal prostate cancer-associated deletion at 10q23.3 corresponds to ~2.06 MB region flanked by BMPR1A and FAS. On a separate cohort comprising an additional 330 tumors, four-color fluorescence in situ hybridization analysis using probes for BMPR1A, FAS, cen(10), and PTEN showed that 132 of 330 (40%) tumors had PTEN loss, 50 (15%) of which were homozygous losses (comprising in total 100 deletion events). Breakpoints between PTEN and BMPR1A or FAS were subsequently mapped in 100 homozygous and 82 hemizygous PTEN losses, revealing that 125/182 PTEN microdeletions occurred within the 940 kB interval between BMPR1A and PTEN. Furthermore, this breakpoint interval coincides with a repeat-rich region of 414 kB containing the SD17 and SD18 segmental duplications, which contain at least 13 homologous inverted repeat sequences. Together, these data suggest that a strong selective growth advantage for loss of PTEN and upregulation of PI3K/AKT, combined with the close proximity of PTEN to a large unstable segment of repeated DNA comprising SD17 and SD18, can lead to recurrent microdeletions of the PTEN gene in prostate cancer. (c) 2011 Wiley Periodicals, Inc. PMID- 22045667 TI - Pentoxifylline for steatohepatitis: magic bullet or smoking gun? PMID- 22045668 TI - Pathogen- or damage-associated molecular patterns during nonalcoholic fatty liver disease development. PMID- 22045669 TI - The antiviral protein viperin inhibits hepatitis C virus replication via interaction with nonstructural protein 5A. AB - The interferon-stimulated gene, viperin, has been shown to have antiviral activity against hepatitis C virus (HCV) in the context of the HCV replicon, although the molecular mechanisms responsible are not well understood. Here, we demonstrate that viperin plays an integral part in the ability of interferon to limit the replication of cell-culture-derived HCV (JFH-1) that accurately reflects the complete viral life cycle. Using confocal microscopy and fluorescence resonance energy transfer (FRET) analysis, we demonstrate that viperin localizes and interacts with HCV nonstructural protein 5A (NS5A) at the lipid-droplet (LD) interface. In addition, viperin also associates with NS5A and the proviral cellular factor, human vesicle-associated membrane protein associated protein subtype A (VAP-A), at the HCV replication complex. The ability of viperin to limit HCV replication was dependent on residues within the C terminus, as well as an N-terminal amphipathic helix. Removal of the amphipathic helix-redirected viperin from the cytosolic face of the endoplasmic reticulum and the LD to a homogenous cytoplasmic distribution, coinciding with a loss of antiviral effect. C-terminal viperin mutants still localized to the LD interface and replication complexes, but did not interact with NS5A proteins, as determined by FRET analysis. CONCLUSION: In conclusion, we propose that viperin interacts with NS5A and the host factor, VAP-A, to limit HCV replication at the replication complex. This highlights the complexity of the host control of viral replication by interferon-stimulated gene expression. PMID- 22045671 TI - Retreatment with telaprevir combination therapy in hepatitis C patients with well characterized prior treatment response. AB - Retreatment with peginterferon alpha and ribavirin (PR) offers a limited chance of sustained virologic response (SVR) in patients who did not achieve SVR with prior PR treatment. This study evaluated the safety and efficacy of telaprevir based treatment in combination with PR in well-characterized patients who did not achieve SVR in the control arms of three Phase II clinical trials. Patients eligible to enroll in this open-label nonrandomized study either met on-treatment criteria for nonresponse or relapsed after 48 weeks of treatment in the control arm of the three Phase II PROVE studies. The initial protocol was a 24-week regimen: 12 weeks of telaprevir and PR followed by an additional 12 weeks of PR. During the study the protocol was amended to extend PR to 48 weeks for patients with previous null response. All other patients with undetectable hepatitis C virus (HCV) RNA at weeks 4 and 12 received 24 weeks of therapy. Those with detectable HCV RNA at weeks 4 or 12 received a total of 48 weeks of therapy. The overall SVR rate was 59% (69/117). SVR rates with T12PR were 37% (19/51) in prior null responders, 55% (16/29) in prior partial responders, 75% (6/8) in prior breakthroughs, and 97% (28/29) in prior relapsers. The overall relapse rate was 16% (13/83). Adverse events were similar to those in previous trials with telaprevir, with 9% of patients discontinuing due to an adverse event (most commonly rash and anemia). CONCLUSION: This study demonstrated the benefit of retreatment with a telaprevir-based regimen for patients with well-characterized nonresponse (null and partial) or relapse to a prior course of PR treatment. PMID- 22045670 TI - Predicting clinical outcomes using baseline and follow-up laboratory data from the hepatitis C long-term treatment against cirrhosis trial. AB - Predicting clinical outcomes in patients with chronic hepatitis C is challenging. We used the hepatitis C long-term treatment against cirrhosis (HALT-C) trial database to develop two models, using baseline values of routinely available laboratory tests together with changes in these values during follow-up to predict clinical decompensation and liver-related death/liver transplant in patients with advanced hepatitis C. Patients randomized to no treatment and who had >= 2-year follow-up without a clinical outcome were included in the analysis. Four variables (platelet count, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ratio, total bilirubin, and albumin) with three categories of change (stable, mild, or severe) over 2 years were analyzed. Cumulative incidence of clinical outcome was determined by Kaplan-Meier analysis and Cox regression was used to evaluate predictors of clinical outcome. In all, 470 patients with 60 events were used to develop models to predict clinical decompensation. Baseline values of all four variables were predictive of decompensation. There was a general trend of increasing outcomes with more marked worsening of laboratory values over 2 years, particularly for patients with abnormal baseline values. A model that included baseline platelet count, AST/ALT ratio, bilirubin, and severe worsening of platelet count, bilirubin, and albumin was the best predictor of clinical decompensation. A total of 483 patients with 79 events were used to evaluate predictors of liver-related death or liver transplant. A model that included baseline platelet count and albumin as well as severe worsening of AST/ALT ratio and albumin was the best predictor of liver related outcomes. CONCLUSION: Both the baseline value and the rapidity in change of the value of routine laboratory variables were shown to be important in predicting clinical outcomes in patients with advanced chronic hepatitis C. PMID- 22045672 TI - Excess liver-related morbidity of chronic hepatitis C patients, who achieve a sustained viral response, and are discharged from care. AB - Our objective was to address two shortfalls in the hepatitis C virus (HCV) literature: (1) Few data exist comparing post-treatment liver-related mortality/morbidity in HCV-sustained virologic response (SVR) patients to non-SVR patients and (2) no data exist examining liver-related morbidity among treatment response subgroups,particularly among noncirrhotic SVR patients, a group who in the main are discharged from care without further follow-up. A retrospective cohort of 1,215 previously naive HCV interferon patients (treated 1996-2007)was derived using HCV clinical databases from nine Scottish clinics. Patients were followed up post-treatment for a mean of 5.3 years. (1) By Cox-regression, liver related hospital episodes (adjusted hazard ratio [AHR]:0.22; 95% confidence interval [CI]: 0.15-0.34) and liver-related mortality [corrected] (AHR: 0.22; 95% CI: 0.09-0.58)were significantly lower in SVR patients, compared to non-SVR patients. (2) Rates of liver-related hospitalization were elevated among all treatment subgroups compared to the general population: Among noncirrhotic SVR patients, adjusted standardized morbidity ratio (SMBR) up to 5.9 (95% CI: 4.5 8.0); among all SVR patients,SMBR up to 10.5 (95% CI: 8.7-12.9); and among non SVR patients, SMBR up to 53.2 (95% CI: 49.4-57.2).Considerable elevation was also noted among patients who have spontaneously resolved their HCV infection(a control group used to gauge the extent to which lifestyle factors, and not chronic HCV, can contribute toliver-related morbidity), SMBR up to 26.8 (95% CI: 25.3-28.3). CONCLUSIONS: (1) Patients achieving an SVR were more than four times less likely to be hospitalized, or die for a liver-related reason, than non-SVR patients and (2) although discharged, noncirrhotic SVR patients harbor a disproportionate burden of liver-related morbidity; up to six times that of the general population. Further, alarming levels of liver-related morbidity in spontaneous resolvers is an important finding warranting further study.. PMID- 22045673 TI - Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C. AB - As there is currently a lack of consensus on the most appropriate dose and duration of peginterferon alfa-2a (PEG-IFNalpha-2a) therapy in hepatitis B e antigen (HBeAg)-positive patients, the efficacy and safety of either 24 or 48 weeks' duration and 90 MUg/week or 180 MUg/week doses were compared. HBeAg positive patients (n = 544; 34% genotype B, 51% genotype C) were randomized to receive PEG-IFNalpha-2a (2 * 2 factorial design) for 24 or 48 weeks and at 90 MUg/week or 180 MUg/week and included in the per-protocol population. The primary efficacy endpoint of the noninferiority study was HBeAg seroconversion 6 months posttreatment. The prespecified odds ratio (OR) noninferiority margin was 1.88 with a one-sided significance level of 0.025. The highest rates of HBeAg seroconversion 6 months posttreatment were in the 180/48 arm (36.2% versus 14.1% 25.8% in the other arms). When the dose and duration arms were pooled, the OR for noninferiority of 24 weeks versus 48 weeks was 2.17 (95% confidence interval [CI] 1.43, 3.31; P = 0.749) and for 90 MUg versus 180 MUg was 1.79 (95% CI 1.18, 2.72; P = 0.410). As the upper limit of the 95% CI of the ORs were >1.88, 24 weeks were inferior to 48 weeks and 90 MUg/week was inferior to 180 MUg/week. The highest rates of response in the 180/48 arm were achieved by patients with HBsAg <1,500 IU/mL at Week 12 (58%) or Week 24 (57%), whereas patients with HBsAg >20,000 IU/mL did not respond. Adverse events were typical of those associated with PEG IFNalpha-2a. CONCLUSION: Compared with lower doses and shorter durations, the licensed PEG-IFNalpha-2a treatment regimen (180 MUg/48 weeks) was the most efficacious and beneficial for HBeAg-positive patients predominantly infected with hepatitis B virus genotypes B or C. PMID- 22045674 TI - Human hepatocellular carcinomas with "Stemness"-related marker expression: keratin 19 expression and a poor prognosis. AB - There is a recently proposed subtype of hepatocellular carcinoma (HCC) that is histologically similar to usual HCC, but characterized by the expression of "stemness"-related markers. A large-scale study on two different cohorts of HCCs was performed to investigate the clinicopathologic features and epithelial mesenchymal transition (EMT)-related protein expression status of this subtype of HCCs. The expression status of stemness-related (e.g., keratin 19 [K19], cluster of differentiation [CD]133, epithelial cell adhesion molecule [EpCAM], and c-kit) and EMT-related markers (e.g., snail, S100A4, urokinase plasminogen activator receptor [uPAR], ezrin, vimentin, E-cadherin, and matrix metalloproteinase [MMP]2) were examined using tissue microarrays from cohort 1 HCCs (n = 137). K19 protein expression in cohort 2 HCCs (n = 237) was correlated with the clinicopathologic parameters and messenger RNA (mRNA) levels of K19, uPAR, VIL2, Snail, Slug, and Twist. K19, EpCAM, c-kit, and CD133 positivity were observed in 18.2%, 35.0%, 34.3%, and 24.8%, respectively. K19 was most frequently expressed in combination with at least one other stemness-related marker (92.0%). K19 positive HCCs demonstrated more frequent major vessel invasion and increased tumor size, compared to K19-negative HCCs (P < 0.05). K19 was most significantly associated with EMT-related protein expression (e.g., vimentin, S100A4, uPAR, and ezrin) (P < 0.05) and a poor prognosis (overall survival: P = 0.018; disease-free survival: P = 0.007) in cohort 1. In cohort 2, HCCs with high K19 mRNA levels demonstrated higher mRNA levels of Snail, uPAR, and MMP2 (P < 0.05). K19-positive HCCs demonstrated more frequent microvascular invasion, fibrous stroma, and less tumor-capsule formation, compared to K19-negative HCCs (P < 0.05). K19 expression was a significant independent predictive factor of poor disease-free survival (P = 0.032). CONCLUSION: K19 was well correlated with clinicopathologic features of tumor aggressiveness, compared to other stemness-related proteins. K19-positive HCCs showed significantly increased EMT-related protein and mRNA expression, suggesting that they may acquire more invasive characteristics, compared to K19 negative HCCs through the up-regulation of EMT-associated genes. PMID- 22045675 TI - Circulating microRNAs as potential markers of human drug-induced liver injury. AB - New biomarkers of liver injury are required in the clinic and in preclinical pharmaceutical evaluation. Previous studies demonstrate that two liver-enriched microRNAs (miR-122 and miR-192) are promising biomarkers of acetaminophen-induced acute liver injury (APAP-ALI) in mice. We have examined these molecules, for the first time, in humans with APAP poisoning. Serum miR-122 and miR-192 were substantially higher in APAP-ALI patients, compared to healthy controls (median DeltaDeltaCt [25th, 75th percentile]) (miR-122: 1,265 [491, 4,270] versus 12.1 [7.0, 26.9], P < 0.0001; miR-192: 6.9 [2.0, 29.2] versus 0.44 [0.30, 0.69], P < 0.0001). A heart-enriched miR-1 showed no difference between APAP-ALI patients and controls, whereas miR-218 (brain-enriched) was slightly higher in the APAP ALI cohort (0.17 [0.07, 0.50] versus 0.07 [0.04, 0.12]; P = 0.01). In chronic kidney disease (CKD) patients, miR-122 and -192 were modestly higher, compared to controls (miR-122: 32.0 [21.1, 40.9] versus 12.1 [7.0, 26.9], P = 0.006; miR-192: 1.2 [0.74, 1.9] versus 0.44 [0.30, 0.69], P = 0.005), but miR-122 and -192 were substantially higher in APAP-ALI patients than CKD patients (miR-122: P < 0.0001; miR-192: P < 0.0004). miR-122 correlated with peak ALT levels in the APAP-ALI cohort (Pearson R = 0.46, P = 0.0005), but not with prothrombin time. miR-122 was also raised alongside peak ALT levels in a group of patients with non-APAP ALI. Day 1 serum miR-122 levels were almost 2-fold higher in APAP-ALI patients who satisfied King's College Criteria (KCC), compared to those who did not satisfy KCC, although this did not reach statistical significance (P = 0.15). CONCLUSION: This work provides the first evidence for the potential use of miRNAs as biomarkers of human drug-induced liver injury. PMID- 22045676 TI - Epimorphin promotes human hepatocellular carcinoma invasion and metastasis through activation of focal adhesion kinase/extracellular signal-regulated kinase/matrix metalloproteinase-9 axis. AB - The high incidence rate of hepatocellular carcinoma (HCC) is mainly the result of frequent metastasis and tumor recurrence. Unfortunately, the underlying molecular mechanisms driving HCC metastasis are still not fully understood. It has been demonstrated that tumor stroma cells contribute to primary tumor growth and metastasis. Within the HCC environment, activated hepatic stellate cells (HSCs) can release a number of molecules and enhance cancer cell proliferation and invasiveness in a paracrine manner. Here, for the first time, we demonstrate that epimorphin (EPM; also called syntaxin-2), an extracellular protein, is strongly elevated in activated HSCs within tumor stroma. We show that knockdown of EPM expression in HSCs substantially abolishes their effects on cancer cell invasion and metastasis. Ectopic expression of EPM in HCC cancer cells enhances their invasiveness; we demonstrate that the cells expressing EPM have markedly increased metastasis potential. Furthermore, EPM-mediated invasion and metastasis of cancer cells is found to require up-regulation of matrix metalloproteinase-9 (MMP-9) through the activation of focal adhesion kinase (FAK)/extracellular signal-regulated kinase (ERK) axis. CONCLUSION: Our results show that EPM, secreted by activated HSCs within HCC stroma, promotes invasion and metastasis of cancer cells by activating MMP-9 expression through the FAK-ERK pathway. PMID- 22045677 TI - Cytological evaluation of bloody nipple discharge fluid. PMID- 22045678 TI - Female gender and mortality after percutaneous coronary intervention: results from a large registry. AB - OBJECTIVES: To investigate if previously reported gender-based outcome disparities following percutaneous coronary intervention (PCI) are applicable in a large and racially-diverse cohort in the drug eluting stent (DES) era. BACKGROUND: It is generally believed that women suffer inferior outcomes compared to men after PCI. However, various strategies have evolved that may have mitigated this imbalance, including improved medical therapy, attention to risk factors, and procedural advances of PCI including DES. METHODS: We identified 13,752 patients (4,761 female, 34.6%) with complete follow-up data who underwent de novo lesion PCI from 04/2003 to 04/2009. Relevant data were extracted from an IRB-approved registry. RESULTS: Compared to males, females were significantly older (69.0 vs. 64.8 years) and more frequently from a minority or non-Caucasian background. Females smoked less, but more were hypertensive and/or diabetic. Women had higher HDL, but also higher LDL cholesterol levels. More women presented with an unstable coronary syndrome and required left anterior descending artery PCI. While unadjusted post-PCI mortality rates were higher in females versus males (30 days, 1.3 vs. 0.8%, P = 0.009; 1 year, 6.1 vs. 4.8%, P = 0.001; 3 year, 10.4 vs. 8.4%, P < 0.0001), multivariable regression analyses failed to identify female gender as an independent predictor of mortality. Propensity-adjusted modeling confirmed that females were not at intrinsically higher risk for mortality after PCI. CONCLUSIONS: Females undergoing PCI exhibit more comorbidities and adverse prognostic factors than males. However, risk adjusted analyses identified that gender is not an independent predictor of mortality after PCI in the DES era. PMID- 22045679 TI - Clinical aspects of neurodegenerative diseases - 15th HUPO BPP Workshop April 8 9, 2011, Bochum, Germany. AB - The HUPO Brain Proteome Project (HUPO BPP) held its 15th workshop in Bochum, Germany, from April 8th to 9th, 2011 directly after the Proteomic Forum 2011 in Berlin. Like on every spring workshop, the focus was more on clinical aspects, so that especially clinicians participated in this workshop. PMID- 22045680 TI - Enabling BioSharing - a report on the Annual Spring Workshop of the HUPO-PSI April 11-13, 2011, EMBL-Heidelberg, Germany. AB - The Annual Spring workshop of the HUPO-PSI was this year held at the EMBL International Centre for Advanced Training (EICAT) in Heidelberg, Germany. Delegates briefly reviewed the successes of the group to date. These include the wide spread implementation of the molecular interaction data exchange formats, PSI-MI XML2.5 and MITAB, and also of mzML, the standard output format for mass spectrometer output data. These successes have resulted in enhanced accessibility to published data, for example the development of the PSICQUIC common query interface for interaction data and the development of databases such as PRIDE to act as public repositories for proteomics data and increased biosharing, through the development of consortia, for example IMEx and ProteomeXchange which will both share the burden of curating the increasing amounts of data being published and work together to make this more accessible to the bench scientist. Work then started over the three days of the workshop, with a focus on advancing the draft format for handling quantitative mass spectrometry data (mzQuantML) and further developing TraML, a standardized format for the exchange and transmission of transition lists for SRM experiments. PMID- 22045683 TI - Hansa: an automated method for discriminating disease and neutral human nsSNPs. AB - Variations are mostly due to nonsynonymous single nucleotide polymorphisms (nsSNPs), some of which are associated with certain diseases. Phenotypic effects of a large number of nsSNPs have not been characterized. Although several methods have been developed to predict the effects of nsSNPs as "disease" or "neutral," there is still a need for development of methods with improved prediction accuracies. We, therefore, developed a support vector machine (SVM) based method named Hansa which uses a novel set of discriminatory features to classify nsSNPs into disease (pathogenic) and benign (neutral) types. Validation studies on a benchmark dataset and further on an independent dataset of well-characterized known disease and neutral mutations show that Hansa outperforms the other known methods. For example, fivefold cross-validation studies using the benchmark HumVar dataset reveal that at the false positive rate (FPR) of 20% Hansa yields a true positive rate (TPR) of 82% that is about 10% higher than the best-known method. Hansa is available in the form of a web server at http://hansa.cdfd.org.in:8080. PMID- 22045684 TI - GSTP1 hypermethylation is associated with reduced protein expression, aggressive disease and prognosis in neuroblastoma. AB - Epigenetic modifications such as methylation of CpG islands in tumor-suppressor gene promoter regions have been associated with tumor development in many human cancers. Using methylation specific multiplex ligation-dependent probe amplification method, we analyzed the methylation status of 35 different genes in 16 neuroblastoma (NB) cell lines and 50 NB tumor samples (NBs), and investigated whether specific hypermethylation was associated with biological and/or clinical parameters. Among the genes found hypermethylated, the effect of GSTP1 hypermethylation on mRNA and protein expression was also explored. The median number of hypermethylated genes was higher in cell lines compared to NBs (5.5 vs. 2). For eight genes, aberrant methylation of CpG-islands in NB was not (ESR1, PAX5, WT1, CADM1, MSH6, and CDKN2B) or very rarely (CDH13 and GSTP1) reported in literature. GSTP1 was found hypermethylated in 44% of the NB cell lines and in 33% of the stage 4-11qLOH -non MYCN-amplified high risk NBs. Hypermethylation was correlated with reduced mRNA and protein expression. In the whole NBs cohort, GSTP1 hypermethylation was less frequently detected (8%), but found to be associated with lower event-free (EFS) and overall survival. Hypermethylation of GSTP1 showed also association with lower EFS in high risk subgroups as stage 4 and older patients (>=547 days). Our results suggest that, as in several adult cancers, aberrant methylation of GSTP1 may contribute to the carcinogenetic process in NB and could be potentially used as a new marker leading to define an ultra-high risk subgroup. PMID- 22045685 TI - Optical coherence tomography assessment of calcified plaque modification after rotational atherectomy. AB - Rotational atherectomy (RA) facilitates stent delivery in highly calcified coronary plaques (CCP). However, lesion ablation by RA in angulated segments may be affected by guidewire bias, leading to a non-uniform plaque modification. Intravascular optical coherence tomography (iOCT) is the highest resolution (~10 MUm axial) intravascular imaging modality available for clinical use; furthermore, near infrared light easily penetrates calcium, with significantly fewer artifacts, including no "blooming effect" as seen by intravascular ultrasound. Therefore, it may pose as a unique tool for serial calcium quantification, as related in this article with pre- and post-RA assessment, allowing accurate characterization of plaque modification, as well as quality of stent deployment. The effects of guidewire bias in the debulking process have not been well documented by iOCT. We present a case of lesion preparation by RA affected by guidewire bias in which iOCT revealed unique insights into CCP modification. PMID- 22045686 TI - Tophaceous gout: a case of destructive joint swelling of the fifth toe. PMID- 22045687 TI - Osteoderm histology of the Pampatheriidae (Cingulata, Xenarthra, Mammalia): Implications for systematics, osteoderm growth, and biomechanical adaptation. AB - Pampatheres are extinct, large-bodied cingulates, which share morphological characters with both armadillos and glyptodonts but are considered to be more closely related to the latter. The osteoderm histology of six pampathere taxa was examined and compared to the histology of other cingulate osteoderms. This study investigates the development and functional adaptation of pampathere osteoderms as well as the phylogenetic relationships of the Pampatheriidae within the Cingulata. We found that pampathere osteoderms share a uniform histological organization based on a basic diploe-like structure. After initial stages of intramembranous growth, metaplastic ossification, that is, the direct incorporation and mineralization of pre-existing protein fibers, plays an important role in osteoderm development and provides information on various kinds of soft tissue otherwise not preserved. The latest stages of osteoderm growth are dominated by periosteal bone formation especially in the superficial cortex. Movable band osteoderms show regular arrangements of incorporated fibers that may increase the resistance of particularly weak areas against strain. The histological composition of pampathere osteoderms is plesiomorphic in its basic structure but shows a number of derived features. A unique array of Sharpey's fibers that are incorporated into the bone matrix at sutured osteoderm margins is interpreted as a synapomorphy of pampatheres. The arrangement of dermal fibers in the deep and superficial cortexes supports the close relationship between pampatheres and glyptodonts. PMID- 22045689 TI - RNA-directed epigenomic reprogramming: an emerging principle of a more targeted cancer therapy? AB - Epigenetic aberrations are recognized as an early and common event during carcinogenesis. This provides a strong rationale for a therapeutic intervention at the epigenetic level. Current epigenetically active drugs, however, lack specificity for particular genomic loci. Better processes for a more targeted manipulation of the cancer epigenome are needed. One option could be the ability of long noncoding RNAs (lncRNAs) to recruit the chromatin modification complexes to particular genomic loci. In consequence, epigenetic variations would not be stochastic but controlled by a directed programme, through which specific groups of genes are regulated by promoter methylation and(or) histone marks, even if located on different chromosomes. lncRNAs are known to be functionally involved in cell fate specification and carcinogenesis. Depleting lncRNAs with oncogenic potential or replacing scarce molecules with tumor suppressor activity could therefore be employed for a specific reprogramming of the epigenome of cancer cells. Apart from the targeted manner and thus specificity, the mode of action by itself could be an advantage of lncRNA-associated therapy. Similar to what happens naturally during cell fate decisions, the whole developmental programme of a cell or particular parts of it could be reset. In consideration of the early onset of epigenetic aberrations, such an approach could even be useful for cancer prevention. PMID- 22045688 TI - FZD6 is a novel gene for human neural tube defects. AB - Neural tube defects (NTDs) are severe malformations of the central nervous system, affecting 1 of 1,000 live births. Mouse models were instrumental in defining the signaling pathways defective in NTDs, including the planar cell polarity (PCP), also called noncanonical Frizzled/Disheveled pathway. Based on the highly penetrant occurrence of NTDs in double Fzd3/Fzd6(-/-) mutant mice, we investigated the role of the human orthologues, FZD3 and FZD6, by resequencing a cohort of 473 NTDs patients and 639 ethnically matched controls. While we could not demonstrate a significant contribution of FZD3 gene, we identified five rare FZD6 variants that were absent in all controls and predicted to have a functional effect by computational analysis: one de novo frameshift mutation (c.1843_1844insA), three missense changes (p.Arg405Gln, p.Arg511Cys p.Arg511His), and one substitution (c.*20C>T) affecting the 3'-untranslated region (UTR) of the gene. The overall rate of predicted deleterious variants of FZD6 was 5.1-fold higher in cases compared to controls, resulting in a significantly increased NTDs mutation burden. This study demonstrates that rare nonsynonymous variants in FZD6 may contribute to NTDs in humans and enlarges the spectrum of mutations that link PCP pathway to NTDs. PMID- 22045691 TI - Presence of benign germ cells in a fine needle aspirate of a spermatocele. PMID- 22045690 TI - Sirolimus- versus paclitaxel-eluting stents for coronary bifurcations intervention: a meta-analysis of five clinical trials. AB - BACKGROUNDS: Relative efficacy and safety of sirolimus-eluting stents (SES) compared with paclitaxel-eluting stents (PES) remains controversial. It is unknown whether there are different effect and safety in coronary bifurcation treatment between SES and PES. OBJECTIVES: The meta-analysis was performed to compare the clinical outcomes of SES and PES in coronary bifurcation intervention. METHODS: Five head-to-head clinical trials of SES versus PES in coronary bifurcation intervention were included. A total of 2,567 patients were involved in the meta-analysis. Mean follow-up period ranged from 6 to 35 months. The primary end points were the need for target lesion revascularization (TLR) and main-branch restenosis. Secondary end points were target vessel revascularization (TVR), cardiac death, major adverse cardiac events (MACE), and stent thrombosis. RESULTS: Compared with PES, SES significantly reduced the risk of TLR (5.3% vs. 10.6%, odds ratio (OR) 0.52; 95% confidence interval (CI) = 0.38 0.70, P < 0.001), main-branch restenosis (4.59% vs. 12.59%, OR 0.31; 95% CI = 0.18-0.55, P < 0.001) and TVR (7.05% vs. 12.57%, OR 0.58; 95% CI = 0.42-0.81, P = 0.001) in coronary bifurcation intervention. In addition, SES group also had a significantly lower incidence of MACE (8.20% vs. 14.13%, OR 0.58; 95% CI = 0.40 0.84, P = 0.004) than PES group. However, there were no statistical difference with respect to the incidence of cardiac death (1.64% vs. 1.09%, P = 0.19) and stent thrombosis (0.84% vs. 1.08%, P = 0.64) between SES and PES groups. CONCLUSIONS: Compared with PES, SES reduced the incidence of TLR, main-branch restenosis and MACE in coronary bifurcation intervention, while the risk of stent thrombosis was similar between SES and PES groups. PMID- 22045692 TI - Comparison between TEWL and laser scanning microscopy measurements for the in vivo characterization of the human epidermal barrier. AB - The analysis of the skin barrier properties is important in various fields of medical treatment and cosmetology. The development and improvement of topically applied substances require an objective analysis of the skin barrier characteristics. Transepidermal water loss (TEWL) measurement is the standard method to characterize epidermal barrier function. The most important disadvantage of this method though, is that it can be affected by different exogenous and endogenous factors, e.g. water content of the applied formulation and room temperature. In the present study, TEWL measurements are compared to laser scanning microscopic (LSM) measurements, concerning the use of these two methods for the non-invasive in vivo characterization of the epidermal barrier function. The investigations were performed prior and subsequent to treatment of dry skin with a gel mixture, developed for skin treatment after radiotherapy for cancer. The present results indicate that in vivo laser scanning microscopy is an appropriate method for the characterization of the skin barrier structure without interference by external factors. PMID- 22045693 TI - Evaluation of rotational control and forces generated during first-order archwire deflections: a comparison of self-ligating and conventional brackets. AB - The purpose of this study was to compare the activation and deactivation forces generated during first-order archwire deflections when different sizes and types of NiTi wires are paired with conventional and self-ligating brackets (SLBs) and to evaluate the rotational control between these same archwire and bracket combinations. Four maxillary premolar SLBs (Damon 3MX, SmartClip, Carriere, and In-Ovation R) and one conventional twin bracket (Victory) were paired with seven archwires [0.014, 0.016, 0.018, 0.016 * 0.022 Ultra Therm (thermal A f 80-90 degrees F), 0.016, 0.018 SPEED Supercable, and 0.017 * 0.025 Turbo]. A cantilever test design was used and 10 trials per bracket/archwire combination were performed. Load/deflection data were captured over 4 mm fi rst-order archwire deflections. Forces generated were compared across all bracket/archwire combinations. Among thermal archwires, for a given deflection, forces increased with increasing archwire size. Supercable archwires displayed less force than their same size thermal counterparts. The Turbo archwire generated force values in between those of 0.016 and 0.018 thermal archwires. Rotational control improved with increasing wire dimensions and for a given archwire size. Rotational control among brackets generally ranked as follows: In-Ovation R > SmartClip > Carriere and Damon 3MX. PMID- 22045694 TI - Malocclusions in children at 3 and 7 years of age: a longitudinal study. AB - The aim of this longitudinal study was to compare the prevalence of malocclusion at ages 3 and 7 years in a sample of children, exploring the hypothesis that prevalence of malocclusion is higher at 3 than at 7 years of age and may be influenced by sucking habits. The study sample comprised 386 children (199 girls and 187 boys), aged 3 years at study start, sourced from three Public Dental Service clinics in Sweden. Malocclusion was diagnosed by clinical examination, using a specific protocol. Data on allergy, traumatic injuries, sucking habits, and breathing pattern including nocturnal breathing disturbances were obtained by means of a questionnaire answered by child and parent in conjunction with the initial and final clinical examination. The overall prevalence of malocclusion decreased significantly, from 70 to 58% (P < 0.0001): predominantly anterior open bite, excessive overjet, and Class III malocclusion. Although high rates of spontaneous correction were also noted for deep bite, Class II malocclusion and posterior and anterior crossbites, new cases developed at almost the same rate; thus, the prevalence was unchanged at the end of the observation period. Anterior open bite and posterior crossbite were the only conditions showing significant associations with sucking habits. The results confirm the hypothesis of higher prevalence of malocclusion at 3 years of age and clearly support the strategy of deferring orthodontic correction of malocclusion until the mixed dentition stage. PMID- 22045695 TI - An airway study of different maxillary and mandibular sagittal positions. AB - The aim of this study was to evaluate the oropharyngeal (OP) and nasal passage (NP) volumes along with various airway variables of patients with normal nasorespiratory functions having different dentofacial skeletal patterns and to evaluate the correlations between different variables and the airway. One hundred and one patients (57 males and 44 females, aged 14-18 years) having pre-treatment cone beam computed tomography images and complete medical records were selected. The patients were divided into five groups as Class I (CI, 81 >= SNA >= 77; 80 >= SNB >= 76; 3 >= ANB >= 1), Class II maxillary protrusion (CIIMaxP, SNA > 81; 80 >= SNB >= 76; ANB > 3), Class II mandibular retrusion (CIIMandR, 81 >= SNA >= 77; SNB < 76; ANB > 3), Class III maxillary retrusion (CIIIMaxR, SNA < 77; 80 >= SNB >= 76; ANB < 1), and Class III mandibular protrusion (CIIIMandP, 81 >= SNA >= 77; SNB > 80; ANB < 1). Posterior airway space, area of the most constricted region at the base of the tongue (minAx), and OP volume were significantly higher for the CIIIMandP group, whereas CIIMandR subjects had the lowest values. The only significant difference for the NP volume was between CI and CIIMandR groups where a smaller volume for the CIIMandR group was observed. The minAx was the variable that presented the best correlation with the OP airway volume. It seems that a detailed analysis of airway may prove to be a valuable diagnostic addition in orthodontics. PMID- 22045696 TI - Classifying external causes of injury: history, current approaches, and future directions. AB - The International Classification of Diseases (ICD) is used to categorize diseases, injuries, and external causes of injury, and it is a key epidemiologic tool enabling storage and retrieval of data from health and vital records to produce core international mortality and morbidity statistics. The ICD is updated periodically to ensure the classification system remains current, and work is now under way to develop the next revision, ICD-11. It has been almost 20 years since the last ICD edition was published and over 60 years since the last substantial structural revision of the external causes chapter. Revision of such a critical tool requires transparency and documentation to ensure that changes made to the classification system are recorded comprehensively for future reference. In this paper, the authors provide a history of the development of external causes classification and outline the external cause structure. They discuss approaches to manage ICD-10 deficiencies and outline the ICD-11 revision approach regarding the development of, rationale for, and implications of proposed changes to the chapter. Through improved capture of external cause concepts in ICD-11, a stronger evidence base will be available to inform injury prevention, treatment, rehabilitation, and policy initiatives to ultimately contribute to a reduction in injury morbidity and mortality. PMID- 22045697 TI - Characterization of inclusion bodies with cytoprotective properties formed by seipinopathy-linked mutant seipin. AB - Gain-of-toxic mutations in the N-glycosylation motif of the seipin/BSCL2 gene (namely, the N88S and S90L mutations) cause autosomal dominant motor neuron diseases, termed 'seipinopathy'. Expressed mutant seipin is improperly folded and accumulates in the endoplasmic reticulum (ER), leading to an unfolded protein response (UPR). Furthermore, cells expressing mutant seipin contain unique cytoplasmic inclusion bodies (IB) that form via a different mechanism from that of ubiquitinated inclusions, or aggresomes. Whether the formation of these IB is pathogenic or protective in neurodegenerative diseases remains unclear. Here, we determined that mutant seipin IB are negative for two well-established ER markers, immunoglobulin-heavy-chain-binding protein and calnexin, indicating a distinct compartmentalization from the main ER, and that mutant seipin IB are formed via a mechanism that is independent of major UPR transducers and ER chaperons. Electron microscopy and coexpression study with variant alpha1 antitrypsin cDNA showed that seipin IB are compatible with unique cytoplasmic vesicles known as ER-derived protective organelles (ERPO). We also obtained evidence that seipin IB exhibit a cytoprotective property via the attenuation of ER stress. These findings suggest that ERPO, such as seipin IB, are a novel adaptation machinery against the accumulation of unfolded proteins in the ER. PMID- 22045698 TI - alpha-Synuclein accumulates in huntingtin inclusions but forms independent filaments and its deficiency attenuates early phenotype in a mouse model of Huntington's disease. AB - Huntington's disease (HD) is the most common of nine inherited neurological disorders caused by expanded polyglutamine (polyQ) sequences which confer propensity to self-aggregate and toxicity to their corresponding mutant proteins. It has been postulated that polyQ expression compromises the folding capacity of the cell which might affect other misfolding-prone proteins. alpha-Synuclein (alpha-syn) is a small neural-specific protein with propensity to self-aggregate that forms Parkinson's disease (PD) Lewy bodies. Point mutations in alpha-syn that favor self-aggregation or alpha-syn gene duplications lead to familial PD, thus indicating that increased alpha-syn aggregation or levels are sufficient to induce neurodegeneration. Since polyQ inclusions in HD and other polyQ disorders are immunopositive for alpha-syn, we speculated that alpha-syn might be recruited as an additional mediator of polyQ toxicity. Here, we confirm in HD postmortem brains and in the R6/1 mouse model of HD the accumulation of alpha-syn in polyQ inclusions. By isolating the characteristic filaments formed by aggregation-prone proteins, we found that N-terminal mutant huntingtin (N-mutHtt) and alpha-syn form independent filamentous microaggregates in R6/1 mouse brain as well as in the inducible HD94 mouse model and that N-mutHtt expression increases the load of alpha-syn filaments. Accordingly, alpha-syn knockout results in a diminished number of N-mutHtt inclusions in transfected neurons and also in vivo in the brain of HD mice. Finally, alpha-syn knockout attenuates body weight loss and early motor phenotype of HD mice. This study therefore demonstrates that alpha syn is a modifier of polyQ toxicity in vivo and raises the possibility that potential PD-related therapies aimed to counteract alpha-syn toxicity might help to slow HD. PMID- 22045699 TI - The homocysteine-inducible endoplasmic reticulum (ER) stress protein Herp counteracts mutant alpha-synuclein-induced ER stress via the homeostatic regulation of ER-resident calcium release channel proteins. AB - Endoplasmic reticulum (ER) stress has been implicated as an initiator or contributing factor in neurodegenerative diseases. The mechanisms that lead to ER stress and whereby ER stress contributes to the degenerative cascades remain unclear but their understanding is critical to devising effective therapies. Here we show that knockdown of Herp (Homocysteine-inducible ER stress protein), an ER stress-inducible protein with an ubiquitin-like (UBL) domain, aggravates ER stress-mediated cell death induced by mutant alpha-synuclein (alphaSyn) that causes an inherited form of Parkinson's disease (PD). Functionally, Herp plays a role in maintaining ER homeostasis by facilitating proteasome-mediated degradation of ER-resident Ca(2+) release channels. Deletion of the UBL domain or pharmacological inhibition of proteasomes abolishes the Herp-mediated stabilization of ER Ca(2+) homeostasis. Furthermore, knockdown or pharmacological inhibition of ER Ca(2+) release channels ameliorates ER stress, suggesting that impaired homeostatic regulation of Ca(2+) channels promotes a protracted ER stress with the consequent activation of ER stress-associated apoptotic pathways. Interestingly, sustained upregulation of ER stress markers and aberrant accumulation of ER Ca(2+) release channels were detected in transgenic mutant A53T-alphaSyn mice. Collectively, these data establish a causative link between impaired ER Ca(2+) homeostasis and chronic ER stress in the degenerative cascades induced by mutant alphaSyn and suggest that Herp is essential for the resolution of ER stress through maintenance of ER Ca(2+) homeostasis. Our findings suggest a therapeutic potential in PD for agents that increase Herp levels or its ER Ca(2+) stabilizing action. PMID- 22045701 TI - Circulating vitamin D and risk of prostate cancer--letter. PMID- 22045700 TI - Risk factors for oral HPV infection among a high prevalence population of HIV positive and at-risk HIV-negative adults. AB - INTRODUCTION: Human papillomavirus (HPV) is an important risk factor for oropharyngeal cancer. Individuals with human immunodeficiency virus (HIV) have higher oral HPV prevalence but the risk factors for oral HPV infection are not well understood for either HIV-positive or HIV-negative individuals. METHODS: This study was nested within the Multicenter AIDS Cohort Study (MACS; men) and Women Interagency HIV Study (WIHS; women) cohorts. Exfoliated oral epithelial cells were collected from 379 HIV-positive and 266 at-risk HIV-negative individuals using a rinse and gargle with Scope mouthwash. Samples were tested for 36 types of HPV DNA using PGMY09/11 consensus primers and reverse line blot hybridization. Risk factors for oral HPV infection were explored using logistic regression with generalized estimating equations in this cross-sectional analysis. RESULTS: Prevalent oral HPV infection was common (34%), including HPV16 infection in 5.7% of participants. HIV-positive individuals had increased odds of prevalent oral HPV infection compared with HIV-negative individuals [adjusted OR = 2.1; 95% confidence interval (CI), 1.6-2.8]. Risk factors for prevalent oral HPV differed in HIV-positive and HIV-negative participants. Among HIV-negative individuals, higher number of recent oral sex or rimming partners were strong risk factors for prevalent oral HPV infection (each P(trend) < 0.01). In contrast, among HIV-positive individuals, lower CD4 T-cell count (P(trend) < 0.001) and higher number of lifetime sexual partners (P(trend) = 0.03) were strong risk factors. CONCLUSIONS: Oral HPV prevalence was elevated in HIV positive individuals after controlling for differences in cigarette smoking and sexual behavior, supporting the possibility that HIV may affect the natural history of oral HPV. IMPACT: Immunosuppression may contribute to increased persistence or progression of oral HPV infection. PMID- 22045703 TI - Antiplatelet and anticoagulant therapy in patients with gastrointestinal bleeding: an 86-year-old woman with peptic ulcer disease. AB - Bleeding in the upper gastrointestinal tract is a common medical problem, with an incidence of 48 to 160 cases per 1000 adults per year and a mortality rate of 5% to 14%. The risk of gastrointestinal bleeding is increased with the use of antiplatelet medications including aspirin and clopidogrel, as well as warfarin or a combination of these medications. The recurrence rate for bleeding in patients who continue to take aspirin after an episode of peptic ulcer disease related bleeding can reach up to 300 cases per 1000 person-years and varies by age, sex, and the use of nonsteroidal anti-inflammatory medications. Using the case of Ms S, an 86-year-old woman who presented to the emergency department with an episode of nonvariceal upper gastrointestinal tract bleeding, we address the management of patients who are receiving antiplatelet or anticoagulation therapy who present with gastrointestinal bleeding, including when to restart antiplatelet or anticoagulation therapy, interventions to reduce the risk of bleeding recurrence, and the potential for drug interactions between clopidogrel and proton pump inhibitors. PMID- 22045704 TI - Olfactory impairment in an adult population: the Beaver Dam Offspring Study. AB - The objective of this study was to determine the prevalence of olfactory impairment and associated risk factors and the effects of olfactory impairment on dietary choices and quality of life. Odor identification was measured in 2838 participants aged 21-84 years (mean 49 years) in the Beaver Dam Offspring Study. The overall prevalence of olfactory impairment was 3.8%, increased with age (from 0.6% in those<35 years to 13.9% among those>=65 years) and was more common in men than women. In a multivariate model age (odds ratio [OR]=1.48, 95% confidence interval [CI]=1.33, 1.64 for every 5-year increase), nasal polyps or deviated septum (OR=2.69, 95% CI=1.62, 4.48), ankle-brachial index<0.9 (OR=3.62, 95% CI=1.45, 9.01), and smoking (women only) (OR=2.43, 95% CI=1.19, 4.98 ever smoked vs. never) were associated with an increased odds of olfactory impairment, whereas higher household income, >=$50,000 versus <$50,000 per year, was associated with a decreased odds of olfactory impairment (OR=0.48, 95% CI=0.31, 0.73). Participants with olfactory impairment were less likely to report that food tasted as good as it used to, or that they experienced food flavors the same. There was no association between olfactory impairment and general health related quality of life, depressive symptoms, or dietary choices. The prevalence of olfactory impairment was low in this largely middle-aged cohort, and some factors associated with olfactory impairment are potentially modifiable. PMID- 22045705 TI - CXCR4-based imaging agents. AB - Chemokine receptor 4 (CXCR4)-chemokine ligand 12 (CXCL12) interactions have been shown to play key roles in cancer cell survival, proliferation, chemotaxis, homing, adhesion, tumor angiogenesis, and resistance to conventional and targeted therapies. Given its extensive involvement in cancer progression, the CXCR4 CXCL12 axis has been considered a therapeutic target. Several inhibitors blocking this signaling cascade are in phase I trials. Because CXCR4 is constitutively expressed in a wide variety of normal tissues, patient stratification and noninvasive monitoring would improve therapeutic outcome and reduce unnecessary toxicities. This review focuses on recent developments in CXCR4-based imaging agents and their potential role in the molecular diagnosis and treatment of cancer. PMID- 22045706 TI - (18)F-FDG PET/CT for monitoring treatment responses to the epidermal growth factor receptor inhibitor erlotinib. AB - Response rates of unselected non-small cell lung cancer (NSCLC) patients to the epidermal growth factor receptor inhibitor erlotinib are low and range from 10% to 20%. Early response assessments are needed to avoid costs and side effects of inefficient treatments. Here we determined whether early changes in tumor uptake of (18)F-FDG can predict progression-free and overall survival in NSCLC patients who are treated with erlotinib. METHODS: Twenty-two patients (6 men, 16 women; mean age +/- SD, 64 +/- 13 y) with stage III or stage IV NSCLC who received erlotinib treatment were enrolled prospectively. (18)F-FDG PET/CT was performed before the initiation of treatment (n = 22), after 2 wk (n = 22), and after 78 +/ 21 d (n = 11). Tumor maximum standardized uptake values were measured for a maximum of 5 lesions for each patient. Tumor responses were classified using modified PET Response Criteria in Solid Tumors (use of maximum standardized uptake values). Median overall survival by Kaplan-Meier analysis was compared between groups using a log-rank test. RESULTS: The overall median time to progression was 52 d (95% confidence interval, 47-57 d). The overall median survival time was 131 d (95% confidence interval, 0-351 d). Patients with progressive metabolic disease on early follow-up PET showed a significantly shorter time to progression (47 vs. 119 d; P < 0.001) and overall survival (87 vs. 828 d; P = 0.01) than patients classified as having stable metabolic disease or partial or complete metabolic response. CONCLUSION: These data suggest that (18)F-FDG PET/CT performed early after the start of erlotinib treatment can help to identify patients who benefit from this targeted therapy. PMID- 22045707 TI - Evaluation of the role of tumor-associated macrophages in an experimental model of peritoneal carcinomatosis using (18)F-FDG PET. AB - PET is widely used at the clinical and preclinical levels for tumor assessment and evaluation of treatment efficacy. Here, we established and took advantage of a preclinical model of peritoneal carcinomatosis to evaluate the contribution of inflammatory infiltrating macrophages in tumor progression that was followed using (18)F-FDG PET. METHODS: Groups of mice with peritoneal carcinomatosis were longitudinally evaluated with (18)F-FDG PET. Intraperitoneal depletion of macrophages was achieved by an approach (i.e., administration of clodronate encapsulated into liposomes) that proved to be safe and effective. Sham liposomes were used in control animal cohorts. RESULTS: (18)F-FDG PET allowed us to detect and monitor peritoneal lesion growth and diffusion. Macrophage-depleted animals showed a substantial reduction in tumor burden paralleled by a decrement in the extent of radioactivity distribution. A significant correlation between lesion dimension and metabolic volume was observed not only in macrophage-depleted but also in sham-treated mice. CONCLUSION: (18)F-FDG PET allowed a noninvasive detection of peritoneal carcinomatosis lesions. Although macrophages play a key role in the early growth and spreading of lesions in the peritoneal cavity, neoplastic cells apparently represent the major player in this system in the uptake of (18)F-FDG. PMID- 22045708 TI - (99)mTc-(CO)(3) His-annexin A5 micro-SPECT demonstrates increased cell death by irinotecan during the vascular normalization window caused by bevacizumab. AB - Colorectal tumors are dependent on angiogenesis for growth, and vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Antiangiogenic drugs can induce a transient normalization of the tumor vasculature with improved delivery of coadministered chemotherapy. The efficacy of antihuman VEGF antibody (bevacizumab) with or without irinotecan was evaluated in a colorectal cancer xenograft using (99m)Tc-(CO)(3) His-annexin A5. METHODS: Colo205-bearing mice were treated with a single dose of bevacizumab (5 mg/kg) during 2, 4, or 6 d. Microvessel density, pericyte coverage (alpha-smooth-muscle actin immunostaining), collagen-covered tumor vessels (Masson trichrome staining), and tumor hypoxic fraction (pimonidazole staining) were determined at the 3 different time points after treatment with bevacizumab. To investigate the possible synergistic effects of combination therapy with bevacizumab and irinotecan, Colo205-bearing mice were treated with a single dose of bevacizumab 2, 4, or 6 d before administration of a single dose of irinotecan (100 mg/kg) or 0.9% NaCl. The apoptosis-detecting radiotracer (99m)Tc-(CO)(3) His-annexin A5 was injected (18.5 MBq) in mice 12, 24, and 48 h after the start of the irinotecan or NaCl treatment, and micro-SPECT was subsequently performed 3.5 h after injection of the radiotracer. Results were correlated to histologic analysis for apoptosis (caspase-3 activation). RESULTS: Four days after bevacizumab administration, microvessel density decreased significantly, and alpha-smooth-muscle actin and collagen-covered vessels, compared with control tumors, were increased, suggesting normalization of the tumor vasculature. Hypoxic fraction was slightly reduced 4 d after treatment with bevacizumab. SPECT analyses demonstrated a significant increase in tumoral (99m)Tc-(CO)(3) His-annexin A5 uptake 4 d after bevacizumab treatment and 24 h after irinotecan administration (232.78 +/- 24.82 percentage injected dose/tumor weight [g]/body weight [kg], P < 0.05), compared with each monotherapy, indicating a synergistic effect of both therapies. CONCLUSION: (99m)Tc-(CO)(3) His-annexin A5 micro-SPECT demonstrates increased antitumor activity of irinotecan during the transient vascular normalization period caused by bevacizumab. Our data outline the importance of timing of combined anti-VEGF treatment with chemotherapy. PMID- 22045709 TI - PET of CXCR4 expression by a (68)Ga-labeled highly specific targeted contrast agent. AB - The overexpression of the chemokine receptor CXCR4 plays an important role in oncology, since together with its endogenous ligand, the stromal cell-derived factor (SDF1-alpha), CXCR4 is involved in tumor development, growth, and organ specific metastasis. As part of our ongoing efforts to develop highly specific CXCR4-targeted imaging probes and with the aim to assess the suitability of this ligand for first proof-of-concept studies in humans, we further evaluated the new (68)Ga-labeled high-affinity cyclic CXCR4 ligand, (68)Ga-CPCR4-2 (cyclo(D-Tyr(1) [NMe]-D-Orn(2)-[4-(aminomethyl) benzoic acid,(68)Ga-DOTA]-Arg(3)-2-Nal(4) Gly(5))). METHODS: Additional biodistribution and competitions studies in vivo, dynamic PET studies, and investigations on the metabolic stability and plasma protein binding were performed in nude mice bearing metastasizing OH1 human small cell lung cancer xenografts. CXCR4 expression on OH1 tumor sections was determined by immunohistochemical staining. RESULTS: (nat)Ga-CPCR4-2 exhibits high CXCR4 affinity with a half maximum inhibitory concentration of 4.99 +/- 0.72 nM. (68)Ga-CPCR4-2 showed high in vivo stability and high and specific tumor accumulation, which was reduced by approximately 80% in competition studies with AMD3100. High CXCR4 expression in tumors was confirmed by immunohistochemical staining. (68)Ga-CPCR4-2 showed low uptake in nontumor tissue and particularly low kidney accumulation despite predominant renal excretion, leading to high contrast delineation of tumors in small-animal PET studies. CONCLUSION: The small and optimized cyclic peptide CPCR4-2 labeled with (68)Ga is a suitable tracer for targeting and imaging of human CXCR4 receptor expression in vivo. The high affinity for CXCR4, its in vivo stability, and the excellent pharmacokinetics recommend the further evaluation of (68)Ga-CPCR4-2 in a proof-of-concept study in humans. PMID- 22045710 TI - Simplified quantification of myocardial flow reserve with (18)F-flurpiridaz: validation with microspheres in a pig model. PMID- 22045711 TI - Oncology. PMID- 22045712 TI - General nuclear medicine. PMID- 22045713 TI - Gathering member feedback on SNM name change. PMID- 22045716 TI - An education opportunity for all: SNM's Mid-Winter Meeting. PMID- 22045714 TI - Notification of proposed SNM Bylaws change. PMID- 22045717 TI - Point-of-care testing parathyroid hormone assay. PMID- 22045719 TI - Effect of nasal tip skin thickness on the outcome of tip refining surgery quantified previously. PMID- 22045721 TI - Chest imaging in H1N1 influenza. PMID- 22045722 TI - Directional connectivity of resting state human fMRI data using cascaded ICA-PDC analysis. AB - BACKGROUND: Directional connectivity measures, such as partial directed coherence (PDC), give us means to explore effective connectivity in the human brain. By utilizing independent component analysis (ICA), the original data-set reduction was performed for further PDC analysis. PURPOSE: To test this cascaded ICA-PDC approach in causality studies of human functional magnetic resonance imaging (fMRI) data. MATERIAL AND METHODS: Resting state group data was imaged from 55 subjects using a 1.5 T scanner (TR 1800 ms, 250 volumes). Temporal concatenation group ICA in a probabilistic ICA and further repeatability runs (n = 200) were overtaken. The reduced data-set included the time series presentation of the following nine ICA components: secondary somatosensory cortex, inferior temporal gyrus, intracalcarine cortex, primary auditory cortex, amygdala, putamen and the frontal medial cortex, posterior cingulate cortex and precuneus, comprising the default mode network components. Re-normalized PDC (rPDC) values were computed to determine directional connectivity at the group level at each frequency. RESULTS: The integrative role was suggested for precuneus while the role of major divergence region may be proposed to primary auditory cortex and amygdala. CONCLUSION: This study demonstrates the potential of the cascaded ICA-PDC approach in directional connectivity studies of human fMRI. PMID- 22045723 TI - Nutrition screening tools: an analysis of the evidence. AB - In response to questions about tools for nutrition screening, an evidence analysis project was developed to identify the most valid and reliable nutrition screening tools for use in acute care and hospital-based ambulatory care settings. An oversight group defined nutrition screening and literature search criteria. A trained analyst conducted structured searches of the literature for studies of nutrition screening tools according to predetermined criteria. Eleven nutrition screening tools designed to detect undernutrition in patients in acute care and hospital-based ambulatory care were identified. Trained analysts evaluated articles for quality using criteria specified by the American Dietetic Association's Evidence Analysis Library. Members of the oversight group assigned quality grades to the tools based on the quality of the supporting evidence, including reliability and validity data. One tool, the NRS-2002, received a grade I, and 4 tools-the Simple Two-Part Tool, the Mini-Nutritional Assessment-Short Form (MNA-SF), the Malnutrition Screening Tool (MST), and Malnutrition Universal Screening Tool (MUST)-received a grade II. The MST was the only tool shown to be both valid and reliable for identifying undernutrition in the settings studied. Thus, validated nutrition screening tools that are simple and easy to use are available for application in acute care and hospital-based ambulatory care settings. PMID- 22045724 TI - Bloodstream infections in patients receiving manufactured parenteral nutrition with vs without lipids: is the use of lipids really deleterious? AB - BACKGROUND: This study compared overall bacterial and bloodstream infection rates in patients receiving premixed parenteral nutrition (PN) with vs without lipid emulsion. METHODS: Data from hospitalized patients who were >=18 years of age and receiving premixed PN between 2005 and 2007 were extracted from the Premier Perspective database. Data were categorized into 2 groups: patients who received premixed PN only and those receiving premixed PN with lipids. Multiple logistic regression was used to adjust for risk factors and potential confounders, reporting the probability of risk for an infection. RESULTS: The group without lipids was observed to have lower rates of both overall bacterial infection (43.5% vs 53.5%) and bloodstream infection (14.5% vs 18.9%). However, after adjusting for baseline characteristics, there were no significant differences in overall risk of bacterial infections (51.4% vs 53.5%; odds ratio [OR] = 1.11; 95% confidence interval [CI], 0.96-1.27) or bloodstream infections (19.6% vs 19.2%; 0.97; 0.81-1.16). In a subset of patients in the intensive care unit for >=3 days, lower overall bacterial infection rates (58.3% vs 67.3%) and bloodstream infection rates (31.0% vs 37.0%) were observed in the group without lipids. After adjustment, there were no significant differences in risk of overall bacterial infection (OR = 0.95; 95% CI, 0.75-1.22) or bloodstream infection (0.92; 0.71 1.19) between the 2 groups. CONCLUSIONS: When administered with premixed PN, lipid emulsion was not significantly associated with an increase in the risk of infectious morbidity when compared to omitting lipids from therapy. PMID- 22045725 TI - The use of observational scales to monitor symptom control and depth of sedation in patients requiring palliative sedation: a systematic review. AB - BACKGROUND: Palliative sedation is the intentional lowering of consciousness of a patient in the last phase of life to relieve suffering from refractory symptoms such as pain, delirium and dyspnoea. AIM: In this systematic review, we evaluated the use of monitoring scales to assess the degree of control of refractory symptoms and/or the depth of the sedation. DESIGN: A database search of PubMed and Embase was performed up to January 2010 using the search terms 'palliative sedation' OR 'terminal sedation'. DATA SOURCES: Retro- and prospective studies as well as reviews and guidelines containing information about monitoring of palliative sedation, written in the English, German or Dutch language were included. RESULTS: The search yielded 264 articles of which 30 were considered relevant. Most studies focused on monitoring refractory symptoms (pain, fatigue or delirium) or the level of awareness to control the level of sedation. Four prospective and one retrospective study used scales validated in other settings: the Numeric Pain Rating Scale, the Visual Analogue Scale, the Memorial Delirium Assessment Scale, the Communication Capacity Scale and Agitation Distress Scale. Only the Community Capacity Scale was partially validated for use in a palliative sedation setting. One guideline described the use of a scale validated in another setting. CONCLUSIONS: A minority of studies reported the use of observational scales to monitor the effect of palliative sedation. Future studies should be focused on establishing proper instruments, most adequate frequency and timing of assessment, and interdisciplinary evaluation of sedation depth and symptom control for palliative sedation. PMID- 22045726 TI - Assessing quality of care for the dying: the development and initial validation of a postal self-completion questionnaire for bereaved relatives. AB - BACKGROUND: Evaluating 'quality of care for the dying' from the patients' perspective has practical and ethical difficulties: an alternative is to use bereaved relatives' views as 'proxy' measures. Currently, within the United Kingdom, there is no validated instrument which specifically examines quality of care in the last days of life or the impact of the Liverpool Care Pathway (LCP) for the Dying Patient. AIM: To develop and validate a questionnaire for use with bereaved relatives assessing the quality of care for patients and families in the last days of life and the immediate period after the bereavement. DESIGN: The instrument, 'Evaluating Care and Health Outcomes - for the Dying' (ECHO-D), was developed in four distinct phases: 1. Question formulation, 2. Expert panel review (n = 6), 3. Wider audience review (n = 25), 4. Pilot, including cognitive pre-testing interviews and preliminary test-retest reliability assessment with bereaved relatives (n = 80) SETTING: The study was conducted within a hospice and an acute hospital involving healthcare professionals, lay members and bereaved relatives. RESULTS: The systematic and robust process of questionnaire development generated evidence for ECHO-D's face and content validity. Response rate for the pilot stage with bereaved relatives, however, was comparatively low (23.4%). Test-retest analysis from the pilot showed moderate or good stability for 13 out of 17 key questions, although small sample numbers limited the interpretation. CONCLUSIONS: ECHO-D is the first instrument specifically to assess 'quality of care for the dying', focussing on the last days of life, and has direct links with the use of the LCP Programme. PMID- 22045727 TI - Methicillin-resistant Staphylococcus aureus (MRSA) management in palliative care units and hospices in Germany: a nationwide survey on patient isolation policies and quality of life. AB - BACKGROUND: For palliative care settings, little is known about the benefits of specific methicillin-resistant Staphylococcus aureus containment regimens and the burdens patient isolation imposes on affected patients, their families, and professional caregivers. AIM: To explore the current practice of MRSA management and its impact on inpatients' quality of life as perceived by professional caregivers. DESIGN: Survey of inpatient palliative care institutions using 23 item questionnaires (infrastructural data: six items, management process: 14, clinical significance: three). SETTING/PARTICIPANTS: All palliative care units (179) and hospices (181) listed in Germany's directory of palliative care services. The chi(2) test was used to test for differences; significance level: p <= 0.05. RESULTS: 229 of 360 questionnaires were returned. More than 90% of the responding institutions employed specific MRSA protocols. Lack of resources was a more important issue for palliative care units than for hospices regarding availability of single rooms (p = 0.002) and staffing (p = 0.004). Compared to hospices, palliative care units more frequently isolated MRSA patients (p = 0.000), actively treated colonization (p = 0.026), assessed the efficacy of eradication (p = 0.000), provided information on MRSA management to patients (p = 0.014) and relatives (p = 0.001), more often restricted patients' activities (p = 0.000), and reported a negative impact on quality of life (p = 0.000). CONCLUSIONS: Rigorously applied MRSA protocols impose significant burdens at the end of life. Research on clinical outcomes including quality of life may identify interventions of questionable benefit. The issue of handling MRSA should be studied as a model for the management of other highly complex conditions and special needs such as patient isolation. PMID- 22045728 TI - Effects of phosphorylation and neuronal activity on the control of synapse formation by synapsin I. AB - Synapsins are synaptic vesicle (SV)-associated proteins that regulate synaptic transmission and neuronal differentiation. At early stages, Syn I and II phosphorylation at Ser9 by cAMP-dependent protein kinase (PKA) and Ca(2+)/calmodulin-dependent protein kinase I/IV modulates axon elongation and SV precursor dynamics. We evaluated the requirement of Syn I for synapse formation by siRNA-mediated knockdown as well as by overexpression of either its wild-type (WT) form or its phosphorylation mutants. Syn1 knockdown at 14 days in vitro caused a decrease in the number of synapses, accompanied by a reduction of SV recycling. Although overexpression of WT Syn I was ineffective, overexpression of its phosphorylation mutants resulted in a complex temporal regulation of synapse density. At early stages of synaptogenesis, phosphomimetic Syn I S9E significantly increased the number of synapses. Conversely, dephosphomimetic Syn I S9A decreased synapse number at more advanced stages. Overexpression of either WT Syn I or its phosphomimetic S9E mutant rescued the decrease in synapse number caused by chronic treatment with tetrodotoxin at early stages, suggesting that Syn I participates in an alternative PKA-dependent mechanism that can compensate for the impairment of the activity-dependent synaptogenic pathway. Altogether these results indicate that Syn I is an important regulator of synapse formation, which adjusts synapse number in response to extracellular signals. PMID- 22045729 TI - Caveolae respond to cell stretch and contribute to stretch-induced signaling. AB - Caveolae are invaginations of the plasma membrane that are formed by caveolins. Caveolar membranes are also enriched in cholesterol, glycosphingolipids and signaling enzymes such as Src kinase. Here we investigate the effect of cell stretch upon caveolar dynamics and signaling. Transfection of C2 myoblasts with caveolin-3-YFP led to the formation of caveolae-like membrane pits 50-100 nm in diameter. Glycosphingolipids became immobilized and tightly packed together within caveolin-rich regions of the plasma membrane. Fluorescence resonance energy transfer (FRET) was used to assess the degree of glycosphingolipid packing. Myoblasts were subjected to a brief (1 minute) stretch on an elastic substratum. Stretch caused a reduction in glycosphingolipid FRET, consistent with a reversible unfolding of caveolar pits in response to membrane tension. Cells expressing caveolin-3-YFP also displayed an enhanced stretch-induced activation of Src kinase, as assessed by immunofluorescence. Repeated stretches resulted in the trafficking and remodeling of caveolin-3-rich membrane domains and accelerated turnover of membrane glycosphingolipids. The stretch-induced unfolding of caveolae, activation of Src and redistribution of caveolin and glycosphingolipids might reflect mechanisms of the cellular adaptation to mechanical stresses. PMID- 22045730 TI - Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle. AB - Accumulation of adipocytes and collagen type-I-producing cells (fibrosis) is observed in muscular dystrophies. The origin of these cells had been largely unknown, but recently we identified mesenchymal progenitors positive for platelet derived growth factor receptor alpha (PDGFRalpha) as the origin of adipocytes in skeletal muscle. However, the origin of muscle fibrosis remains largely unknown. In this study, clonal analyses show that PDGFRalpha(+) cells also differentiate into collagen type-I-producing cells. In fact, PDGFRalpha(+) cells accumulated in fibrotic areas of the diaphragm in the mdx mouse, a model of Duchenne muscular dystrophy. Furthermore, mRNA of fibrosis markers was expressed exclusively in the PDGFRalpha(+) cell fraction in the mdx diaphragm. Importantly, TGF-beta isoforms, known as potent profibrotic cytokines, induced expression of markers of fibrosis in PDGFRalpha(+) cells but not in myogenic cells. Transplantation studies revealed that fibrogenic PDGFRalpha(+) cells mainly derived from pre-existing PDGFRalpha(+) cells and that the contribution of PDGFRalpha(-) cells and circulating cells was limited. These results indicate that mesenchymal progenitors are the main origin of not only fat accumulation but also fibrosis in skeletal muscle. PMID- 22045731 TI - Ligand of Numb proteins LNX1p80 and LNX2 interact with the human glycoprotein CD8alpha and promote its ubiquitylation and endocytosis. AB - E3 ubiquitin ligases give specificity to the ubiquitylation process by selectively binding substrates. Recently, their function has emerged as a crucial modulator of T-cell tolerance and immunity. However, substrates, partners and mechanism of action for most E3 ligases remain largely unknown. In this study, we identified the human T-cell co-receptor CD8 alpha-chain as binding partner of the ligand of Numb proteins X1 (LNX1p80 isoform) and X2 (LNX2). Both LNX mRNAs were found expressed in T cells purified from human blood, and both proteins interacted with CD8alpha in human HPB-ALL T cells. By using an in vitro assay and a heterologous expression system we showed that the interaction is mediated by the PDZ (PSD95-DlgA-ZO-1) domains of LNX proteins and the cytosolic C-terminal valine motif of CD8alpha. Moreover, CD8alpha redistributed LNX1 or LNX2 from the cytosol to the plasma membrane, whereas, remarkably, LNX1 or LNX2 promoted CD8alpha ubiquitylation, downregulation from the plasma membrane, transport to the lysosomes, and degradation. Our findings highlight the function of LNX proteins as E3 ligases and suggest a mechanism of regulation for CD8alpha localization at the plasma membrane by ubiquitylation and endocytosis. PMID- 22045732 TI - De novo assembly of a PML nuclear subcompartment occurs through multiple pathways and induces telomere elongation. AB - Telomerase-negative tumor cells use an alternative lengthening of telomeres (ALT) pathway that involves DNA recombination and repair to maintain their proliferative potential. The cytological hallmark of this process is the accumulation of promyelocytic leukemia (PML) nuclear protein at telomeric DNA to form ALT-associated PML bodies (APBs). Here, the de novo formation of a telomeric PML nuclear subcompartment was investigated by recruiting APB protein components. We show that functionally distinct proteins were able to initiate the formation of bona fide APBs with high efficiency in a self-organizing and self-propagating manner. These included: (1) PML and Sp100 as the constituting components of PML nuclear bodies, (2) telomere repeat binding factors 1 and 2 (TRF1 and TRF2, respectively), (3) the DNA repair protein NBS1 and (4) the SUMO E3 ligase MMS21, as well as the isolated SUMO1 domain, through an interacting domain of another protein factor. By contrast, the repair factors Rad9, Rad17 and Rad51 were less efficient in APB nucleation but were recruited to preassembled APBs. The artificially created APBs induced telomeric extension through a DNA repair mechanism, as inferred from their colocalization with sites of non-replicative DNA synthesis and histone H2A.X phosphorylation, and an increase of the telomere repeat length. These activities were absent after recruitment of the APB factors to a pericentric locus and establish APBs as functional intermediates of the ALT pathway. PMID- 22045733 TI - Peroxiredoxin-controlled G-CSF signalling at the endoplasmic reticulum-early endosome interface. AB - Reactive oxygen species (ROS) regulate growth factor receptor signalling at least in part by inhibiting oxidation-sensitive phosphatases. An emerging concept is that ROS act locally to affect signal transduction in different subcellular compartments and that ROS levels are regulated by antioxidant proteins at the same local level. Here, we show that the ER-resident antioxidant peroxiredoxin 4 (Prdx4) interacts with the cytoplasmic domain of the granulocyte colony stimulating factor receptor (G-CSFR). This interaction occurs when the activated G-CSFR resides in early endosomes. Prdx4 inhibits G-CSF-induced signalling and proliferation in myeloid progenitors, depending on its redox-active cysteine core. Protein tyrosine phosphatase 1b (Ptp1b) appears to be a major downstream effector controlling these responses. Conversely, Ptp1b might keep Prdx4 active by reducing its phosphorylation. These findings unveil a new signal transduction regulatory circuitry involving redox-controlled processes in the ER and activated cytokine receptors in endosomes. PMID- 22045734 TI - Integrity of the network sarcoplasmic reticulum in skeletal muscle requires small ankyrin 1. AB - Small ankyrin 1 (sAnk1; Ank1.5) is a ~20 kDa protein of striated muscle that concentrates in the network compartment of the sarcoplasmic reticulum (nSR). We used siRNA targeted to sAnk1 to assess its role in organizing the sarcoplasmic reticulum (SR) of skeletal myofibers in vitro. siRNA reduced sAnk1 mRNA and protein levels and disrupted the organization of the remaining sAnk1. Sarcomeric proteins were unchanged, but two other proteins of the nSR, SERCA and sarcolipin, decreased significantly in amount and segregated into distinct structures containing sarcolipin and sAnk1, and SERCA, respectively. Exogenous sAnk1 restored SERCA to its normal distribution. Ryanodine receptors and calsequestrin in the junctional SR, and L-type Ca(2+) channels in the transverse tubules were not reduced, although their striated organization was mildly altered. Consistent with the loss of SERCA, uptake and release of Ca(2+) were significantly inhibited. Our results show that sAnk1 stabilizes the nSR and that its absence causes the nSR to fragment into distinct membrane compartments. PMID- 22045735 TI - Protein aggregation of SERCA2 mutants associated with Darier disease elicits ER stress and apoptosis in keratinocytes. AB - Mutations in sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) underlie Darier disease (DD), a dominantly inherited skin disorder characterized by loss of keratinocyte adhesion (acantholysis) and abnormal keratinization (dyskeratosis) resulting in characteristic mucocutaneous abnormalities. However, the molecular pathogenic mechanism by which these changes influence keratinocyte adhesion and viability remains unknown. We show here that SERCA2 protein is extremely sensitive to endoplasmic reticulum (ER) stress, which typically results in aggregation and insolubility of the protein. Depletion of ER calcium stores is not necessary for the aggregation but accelerates the progression. Systematic analysis of diverse mutants identical to those found in DD patients demonstrated that the ER stress initiator is the SERCA2 mutant protein itself. These SERCA2 proteins were found to be less soluble, to aggregate and to be more polyubiquitinylated. After transduction into primary human epidermal keratinocytes, mutant SERCA2 aggregates elicited ER stress, caused increased numbers of cells to round up and detach from the culture plate, and induced apoptosis. These mutant induced events were exaggerated by increased ER stress. Furthermore, knockdown SERCA2 in keratinocytes rendered the cells resistant to apoptosis induction. These features of SERCA2 and its mutants establish a mechanistic base to further elucidate the molecular pathogenesis underlying acantholysis and dyskeratosis in DD. PMID- 22045736 TI - Bartonella henselae engages inside-out and outside-in signaling by integrin beta1 and talin1 during invasome-mediated bacterial uptake. AB - The VirB/D4 type IV secretion system (T4SS) of the bacterial pathogen Bartonella henselae (Bhe) translocates seven effector proteins (BepA-BepG) into human cells that subvert host cellular functions. Two redundant pathways dependent on BepG or the combination of BepC and BepF trigger the formation of a bacterial uptake structure termed the invasome. Invasome formation is a multi-step process consisting of bacterial adherence, effector translocation, aggregation of bacteria on the cell surface and engulfment, and eventually, complete internalization of the bacterial aggregate occurs in an F-actin-dependent manner. In the present study, we show that Bhe-triggered invasome formation depends on integrin-beta1-mediated signaling cascades that enable assembly of the F-actin invasome structure. We demonstrate that Bhe interacts with integrin beta1 in a fibronectin- and VirB/D4 T4SS-independent manner and that activated integrin beta1 is essential for both effector translocation and the actin rearrangements leading to invasome formation. Furthermore, we show that talin1, but not talin2, is required for inside-out activation of integrin beta1 during invasome formation. Finally, integrin-beta1-mediated outside-in signaling by FAK, Src, paxillin and vinculin is necessary for invasome formation. This is the first example of a bacterial entry process that fully exploits the bi-directional signaling capacity of integrin receptors in a talin1-specific manner. PMID- 22045737 TI - Live-cell fluorescence correlation spectroscopy dissects the role of coregulator exchange and chromatin binding in retinoic acid receptor mobility. AB - The retinoic acid receptor (RAR) is a member of the nuclear receptor superfamily. This ligand-inducible transcription factor binds to DNA as a heterodimer with the retinoid X receptor (RXR) in the nucleus. The nucleus is a dynamic compartment and live-cell imaging techniques make it possible to investigate transcription factor action in real-time. We studied the diffusion of EGFP-RAR by fluorescence correlation spectroscopy (FCS) to uncover the molecular interactions determining receptor mobility. In the absence of ligand, we identified two distinct species with different mobilities. The fast component has a diffusion coefficient of D(1)=1.8-6.0 MUm(2)/second corresponding to small oligomeric forms, whereas the slow component with D(2)=0.05-0.10 MUm(2)/second corresponds to interactions of RAR with the chromatin or other large structures. The RAR ligand-binding-domain fragment also has a slow component, probably as a result of indirect DNA-binding through RXR, with lower affinity than the intact RAR-RXR complex. Importantly, RAR-agonist treatment shifts the equilibrium towards the slow population of the wild-type receptor, but without significantly changing the mobility of either the fast or the slow population. By using a series of mutant forms of the receptor with altered DNA- or coregulator-binding capacity we found that the slow component is probably related to chromatin binding, and that coregulator exchange, specifically the binding of the coactivator complex, is the main determinant contributing to the redistribution of RAR during ligand activation. PMID- 22045738 TI - Ultrastructural study of transcription factories in mouse erythroblasts. AB - RNA polymerase II (RNAPII) transcription has been proposed to occur at transcription factories; nuclear focal accumulations of the active, phosphorylated forms of RNAPII. The low ratio of transcription factories to active genes and transcription units suggests that genes must share factories. Our previous analyses using light microscopy have indicated that multiple genes could share the same factory. Furthermore, we found that a small number of specialized transcription factories containing high levels of the erythroid specific transcription factor KLF1 preferentially transcribed a network of KLF1 regulated genes. Here we used correlative light microscopy in combination with energy filtering transmission electron microscopy (EFTEM) and electron microscopy in situ hybridization (EMISH) to analyse transcription factories, transcribing genes, and their nuclear environments at the ultrastructural level in ex vivo mouse foetal liver erythroblasts. We show that transcription factories in this tissue can be recognized as large nitrogen-rich structures with a mean diameter of 130 nm, which is considerably larger than that previously seen in transformed cultured cell lines. We show that KLF1-specialized factories are significantly larger, with the majority of measured factories occupying the upper 25th percentile of this distribution with an average diameter of 174 nm. In addition, we show that very highly transcribed genes associated with erythroid differentiation tend to occupy and share the largest factories with an average diameter of 198 nm. Our results suggest that individual factories are dynamically organized and able to respond to the increased transcriptional load imposed by multiple highly transcribed genes by significantly increasing in size. PMID- 22045739 TI - Rab35 regulates phagosome formation through recruitment of ACAP2 in macrophages during FcgammaR-mediated phagocytosis. AB - Phagosome formation and subsequent maturation are complex sequences of events that involve actin cytoskeleton remodeling and membrane trafficking. Here, we demonstrate that the Ras-related protein Rab35 is involved in the early stage of FcgammaR-mediated phagocytosis in macrophages. Live-cell image analysis revealed that Rab35 was markedly concentrated at the membrane where IgG-opsonized erythrocytes (IgG-Es) are bound. Rab35 silencing by RNA interference (RNAi) or the expression of GDP- or GTP-locked Rab35 mutant drastically reduced the rate of phagocytosis of IgG-Es. Actin-mediated pseudopod extension to form phagocytic cups was disturbed by the Rab35 silencing or the expression of GDP-Rab35, although initial actin assembly at the IgG-E binding sites was not inhibited. Furthermore, GTP-Rab35-dependent recruitment of ACAP2, an ARF6 GTPase-activating protein, was shown in the phagocytic cup formation. Concomitantly, overexpression of ACAP2 along with GTP-locked Rab35 showed a synergistic inhibitory effect on phagocytosis. It is likely that Rab35 regulates actin-dependent phagosome formation by recruiting ACAP2, which might control actin remodeling and membrane traffic through ARF6. PMID- 22045740 TI - Nucleostemin inhibits TRF1 dimerization and shortens its dynamic association with the telomere. AB - TRF1 is a key component of the telomere-capping complex and binds double-strand telomeric DNA as homodimers. So far, it is not clear whether TRF1 dimerization coincides with its telomere binding or is actively controlled before it binds the telomere, and in the latter case, how this event might affect its telomere association. We previously found that TRF1 dimerization and its telomere binding can be increased by GNL3L, which is the vertebrate paralogue of nucleostemin (NS). Here, we show that NS and GNL3L bind TRF1 directly but competitively through two separate domains of TRF1. In contrast to GNL3L, NS prevents TRF1 dimerization through a mechanism not determined by its ability to displace TRF1 bound GNL3L. Furthermore, NS is capable of shortening the dynamic association of TRF1 with the telomere in normal and TRF2(DeltaBDeltaM)-induced telomere-damaged cells without affecting the amount of telomere-bound TRF1 proteins in vivo. Importantly, NS displays a protective function against the formation of telomere dysfunction-induced foci. This work demonstrates that TRF1 dimerization is actively and oppositely regulated by NS and GNL3L extrachromosomally. Changing the relative amount of TRF1 monomers versus dimers in the nucleoplasm might affect the dynamic association of TRF1 with the telomere and the repair of damaged telomeres. PMID- 22045741 TI - Partnering with health care payers to advance the science of quality improvement: lessons from the field. PMID- 22045742 TI - COPD Progression and individual rates of change in FEV1 and the BODE index. PMID- 22045743 TI - Pulmonary artery thrombosis: another piece to the acute chest syndrome puzzle. PMID- 22045744 TI - Ventilator-associated pneumonia and the gastropulmonary route of infection: a pendulum. PMID- 22045745 TI - Early-onset pneumonia after cardiac arrest: an unintended consequence of therapeutic hypothermia? PMID- 22045746 TI - Obesity and primary graft dysfunction: weighing the evidence. PMID- 22045747 TI - Loop gain: can it help close the heart failure-periodic breathing loop? PMID- 22045748 TI - Expiratory lymphatic sacs. PMID- 22045749 TI - Necrotizing bronchiolitis in influenza A of swine origin (H1N1). PMID- 22045750 TI - Risk and incidence of pulmonary diseases among HIV-infected patients in the era of combination antiretroviral therapy. PMID- 22045751 TI - Low bone mineral density in emphysema: epiphenomenon of a wasting phenotype? PMID- 22045752 TI - Cystic fibrosis upper airways primary colonization with Pseudomonas aeruginosa: eradicated by sinonasal antibiotic inhalation. PMID- 22045753 TI - The diversity of sex steroid action: novel functions of hydroxysteroid (17beta) dehydrogenases as revealed by genetically modified mouse models. AB - Disturbed action of sex steroid hormones, i.e. androgens and estrogens, is involved in the pathogenesis of various severe diseases in humans. Interestingly, recent studies have provided data further supporting the hypothesis that the circulating hormone concentrations do not explain all physiological and pathological processes observed in hormone-dependent tissues, while the intratissue sex steroid concentrations are determined by the expression of steroid metabolising enzymes in the neighbouring cells (paracrine action) and/or by target cells themselves (intracrine action). This local sex steroid production is also a valuable treatment option for developing novel therapies against hormonal diseases. Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) compose a family of 14 enzymes that catalyse the conversion between the low-active 17-keto steroids and the highly active 17beta-hydroxy steroids. The enzymes frequently expressed in sex steroid target tissues are, thus, potential drug targets in order to lower the local sex steroid concentrations. The present review summarises the recent data obtained for the role of HSD17B1, HSD17B2, HSD17B7 and HSD17B12 enzymes in various metabolic pathways and their physiological and pathophysiological roles as revealed by the recently generated genetically modified mouse models. Our data, together with that provided by others, show that, in addition to having a role in sex steroid metabolism, several of these HSD17B enzymes possess key roles in other metabolic processes: for example, HD17B7 is essential for cholesterol biosynthesis and HSD17B12 is involved in elongation of fatty acids. Additional studies in vitro and in vivo are to be carried out in order to fully define the metabolic role of the HSD17B enzymes and to evaluate their value as drug targets. PMID- 22045754 TI - Expression and uptake of the thyroxine-binding protein transthyretin is regulated by oxygen in primary trophoblast placental cells. AB - Transplacental delivery of maternal thyroid hormones to the fetus, in particular thyroxine (T4), is critical in ensuring normal fetal neurological development. The fetus relies on maternal T4 till around 16 weeks gestation, but mechanisms of placental T4 transport are not yet fully elucidated. Placenta produces, secretes and takes up the thyroid hormone-binding protein transthyretin (TTR). Many placental genes are regulated by oxygen levels, which are relatively low (1%) in the early first trimester, rising to 3% in the mid first trimester and 8% in the early second trimester and thereafter. We examined the expression and uptake of TTR in isolated primary human placental cytotrophoblast cells cultured under different oxygen concentrations (1, 3, 8, 21% O2 and 200 MUM desferrioxamine (DFO)) for 24 h. We observed sevenfold higher expression of TTR mRNA and protein levels at 1% O2 than at 8 and 21% O2. Significant increases were observed after culture at 3% O2 and following DFO treatment. We observed significantly higher uptake of 125I-TTR and Alexa-594-TTR when cells were cultured at 1 and 3% O2 and in the presence of 200 MUM DFO than at 8 and 21% O2. When JEG-3 choriocarcinoma cells were transfected with TTR promoter reporter constructs, increased luciferase activity was measured in cells cultured at 1 and 3% O2 in comparison to 8 and 21% O2. We conclude that placental TTR expression and uptake is increased by the relative hypoxia observed in the first trimester of pregnancy, a time when materno-fetal T4 transfer is the sole source of fetal T4. PMID- 22045755 TI - The emerging role of C/EBPs in glucocorticoid signaling: lessons from the lung. AB - Glucocorticoids (GCs) have been successfully used in the treatment of inflammatory diseases for decades. However, there is a relative GC resistance in several inflammatory lung disorders, such as chronic obstructive pulmonary disease (COPD), but still the mechanism(s) behind this unresponsiveness remains unknown. Interaction between transcription factors and the GC receptor contribute to GC effects but may also provide mechanisms explaining steroid resistance. CCAAT/enhancer-binding protein (C/EBP) transcription factors are important regulators of pulmonary gene expression and have been implicated in inflammatory lung diseases such as asthma, pulmonary fibrosis, cystic fibrosis, sarcoidosis, and COPD. In addition, several studies have indicated a role for C/EBPs in mediating GC effects. In this review, we discuss the different mechanisms of GC action as well as the function of the lung-enriched members of the C/EBP transcription factor family. We also summarize the current knowledge of the role of C/EBP transcription factors in mediating the effects of GCs, with emphasis on pulmonary effects, and their potential role in mediating GC resistance. PMID- 22045756 TI - The cover. Pardon in Brittany. PMID- 22045757 TI - A piece of my mind. The quiet epidemic. PMID- 22045758 TI - Scientists seek strategies to prevent Clostridium difficile infections. PMID- 22045759 TI - FDA advisory decision highlights some problems inherent in pragmatic trials. PMID- 22045760 TI - Review sizes up therapies for juvenile arthritis. PMID- 22045761 TI - Adherence to a healthy lifestyle and sudden cardiac death among women. PMID- 22045762 TI - Gender-based violence in women and mental disorders. PMID- 22045763 TI - Sleep-disordered breathing and cognitive impairment in older women. PMID- 22045764 TI - Organ transplantation and regulation in China. PMID- 22045765 TI - Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies. AB - CONTEXT: A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions. OBJECTIVE: To describe outcomes of patients 60 years or older after receiving minimally toxic nonmyeloablative allogeneic HCT. DESIGN, SETTING, AND PARTICIPANTS: From 1998 to 2008, 372 patients aged 60 to 75 years were enrolled in prospective clinical HCT trials at 18 collaborating institutions using conditioning with low-dose total body irradiation alone or combined with fludarabine, 90 mg/m(2), before related (n = 184) or unrelated (n = 188) donor transplants. Postgrafting immunosuppression included mycophenolate mofetil and a calcineurin inhibitor. MAIN OUTCOME MEASURES: Overall and progression-free survival were estimated by Kaplan-Meier method. Cumulative incidence estimates were calculated for acute and chronic graft-vs-host disease, toxicities, achievement of full donor chimerism, complete remission, relapse, and nonrelapse mortality. Hazard ratios (HRs) were estimated from Cox regression models. RESULTS: Overall, 5-year cumulative incidences of nonrelapse mortality and relapse were 27% (95% CI, 22%-32%) and 41% (95% CI, 36%-46%), respectively, leading to 5-year overall and progression-free survival of 35% (95% CI, 30%-40%) and 32% (95% CI, 27%-37%), respectively. These outcomes were not statistically significantly different when stratified by age groups. Furthermore, increasing age was not associated with increases in acute or chronic graft-vs-host disease or organ toxicities. In multivariate models, HCT specific comorbidity index scores of 1 to 2 (HR, 1.58 [95% CI, 1.08-2.31]) and 3 or greater (HR, 1.97 [95% CI, 1.38-2.80]) were associated with worse survival compared with an HCT-specific comorbidity index score of 0 (P = .003 overall). Similarly, standard relapse risk (HR, 1.67 [95% CI, 1.10-2.54]) and high relapse risk (HR, 2.22 [95% CI, 1.43-3.43]) were associated with worse survival compared with low relapse risk (P < .001 overall). CONCLUSION: Among patients aged 60 to 75 years treated with nonmyeloablative allogeneic HCT, 5-year overall and progression-free survivals were 35% and 32%, respectively. PMID- 22045766 TI - Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk. AB - CONTEXT: Multiple studies have linked alcohol consumption to breast cancer risk, but the risk of lower levels of consumption has not been well quantified. In addition, the role of drinking patterns (ie, frequency of drinking and "binge" drinking) and consumption at different times of adult life are not well understood. OBJECTIVE: To evaluate the association of breast cancer with alcohol consumption during adult life, including quantity, frequency, and age at consumption. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study of 105,986 women enrolled in the Nurses' Health Study followed up from 1980 until 2008 with an early adult alcohol assessment and 8 updated alcohol assessments. MAIN OUTCOME MEASURES: Relative risks of developing invasive breast cancer. RESULTS: During 2.4 million person-years of follow-up, 7690 cases of invasive breast cancer were diagnosed. Increasing alcohol consumption was associated with increased breast cancer risk that was statistically significant at levels as low as 5.0 to 9.9 g per day, equivalent to 3 to 6 drinks per week (relative risk, 1.15; 95% CI, 1.06-1.24; 333 cases/100,000 person-years). Binge drinking, but not frequency of drinking, was associated with breast cancer risk after controlling for cumulative alcohol intake. Alcohol intake both earlier and later in adult life was independently associated with risk. CONCLUSIONS: Low levels of alcohol consumption were associated with a small increase in breast cancer risk, with the most consistent measure being cumulative alcohol intake throughout adult life. Alcohol intake both earlier and later in adult life was independently associated with risk. PMID- 22045768 TI - Update: A 43-year-old man with angina, elevated troponin, and lateral ST depression: management of acute coronary syndromes. PMID- 22045767 TI - Spectrum of cancer risk among US solid organ transplant recipients. AB - CONTEXT: Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology. OBJECTIVE: To describe the overall pattern of cancer following solid organ transplantation. DESIGN, SETTING, AND PARTICIPANTS: Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries. MAIN OUTCOME MEASURES: Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population. RESULTS: The registry linkages yielded data on 175,732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10,656 cases and an incidence of 1375 per 100,000 person years (SIR, 2.10 [95% CI, 2.06-2.14]; EAR, 719.3 [95% CI, 693.3-745.6] per 100,000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100,000 person-years; SIR, 7.54 [95% CI, 7.17-7.93]; EAR, 168.3 [95% CI, 158.6 178.4] per 100,000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100,000 person-years; SIR, 1.97 [95% CI, 1.86-2.08]; EAR, 85.3 [95% CI, 76.2-94.8] per 100,000 person-years), liver (n = 930; incidence: 120.0 per 100,000 person-years; SIR, 11.56 [95% CI, 10.83-12.33]; EAR, 109.6 [95% CI, 102.0 117.6] per 100,000 person-years), and kidney (n = 752; incidence: 97.0 per 100,000 person-years; SIR, 4.65 [95% CI, 4.32-4.99]; EAR, 76.1 [95% CI, 69.3 83.3] per 100,000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 [95% CI, 5.18-7.21]) but also increased among other recipients (kidney: SIR, 1.46 [95% CI, 1.34-1.59]; liver: SIR, 1.95 [95% CI, 1.74 2.19]; and heart: SIR, 2.67 [95% CI, 2.40-2.95]). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 [95% CI, 40.90-46.91]), who manifested exceptional risk in the first 6 months (SIR, 508.97 [95% CI, 474.16-545.66]) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 [95% CI, 1.57 3.04]). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 [95% CI, 6.12-7.23]) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 [95% CI, 1.40-2.29]) and heart recipients (SIR, 2.90 [95% CI, 2.32-3.59]). CONCLUSION: Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers. PMID- 22045769 TI - Academic medical centers--organizational integration and discipline through contractual and firm models. PMID- 22045770 TI - Detours on the road to personalized medicine: barriers to biomarker validation and implementation. PMID- 22045771 TI - Overcoming the age barrier in hematopoietic stem cell transplantation: progress, but still a long way to go. PMID- 22045772 TI - Alcohol and risk of breast cancer. PMID- 22045773 TI - Indurated, purplish plaque on a newborn. PMID- 22045774 TI - JAMA patient page. Plantar fasciitis. PMID- 22045775 TI - Notice of retraction. Isolation and characterization of multipotent progenitor cells from the human fetal aorta wall. PMID- 22045776 TI - Speed judgments of three-dimensional motion incorporate extraretinal information. AB - When tracking an object moving in depth, the visual system should take changes of eye vergence into account to judge the object's 3D speed correctly. Previous work has shown that extraretinal information about changes in eye vergence is exploited when judging the sign of 3D motion. Here, we ask whether extraretinal signals also affect judgments of 3D speed. Observers judged the speed of a small target surrounded by a large background. To manipulate extraretinal information, we varied the vergence demand of the entire stimulus sinusoidally over time. At different phases of vergence pursuit, we changed the disparity of the target relative to the background, leading observers to perceive approaching target motion. We determined psychometric functions for the target's approach speed when the eyes were (1) converging, (2) diverging, (3) maximally converged (near), and (4) maximally diverged (far). The target's motion was reported as faster during convergence and slower during divergence but perceived speed was little affected at near or far vergence positions. Thus, 3D speed judgments are affected by extraretinal signals about changes in eye rotation but appear unaffected by the absolute orientation of the eyes. We develop a model that accounts for observers' judgments by taking a weighted average of the retinal and extraretinal signals to target motion. PMID- 22045777 TI - Estimating distance during self-motion: a role for visual-vestibular interactions. AB - A fundamental challenge for the visual system is to extract the 3D spatial structure of the environment. When an observer translates without moving the eyes, the retinal speed of a stationary object is related to its distance by a scale factor that depends on the velocity of the observer's self-motion. Here, we aim to test whether the brain uses vestibular cues to self-motion to estimate distance to stationary surfaces in the environment. This relationship was systematically probed using a two-alternative forced-choice task in which distance perceived from monocular image motion during passive body translation was compared to distance perceived from binocular disparity while subjects were stationary. We show that perceived distance from motion depended on both observer velocity and retinal speed. For a given head speed, slower retinal speeds led to the perception of farther distances. Likewise, for a given retinal speed, slower head speeds led to the perception of nearer distances. However, these relationships were weak in some subjects and absent in others, and distance estimated from self-motion and retinal image motion was substantially compressed relative to distance estimated from binocular disparity. Overall, our findings suggest that the combination of retinal image motion and vestibular signals related to head velocity can provide a rudimentary capacity for distance estimation. PMID- 22045779 TI - Rejected and excluded forevermore, but even more devoted: irrevocable ostracism intensifies loyalty to the group among identity-fused persons. AB - When people are ostrasized (i.e., rejected and excluded) by either an outgroup or an ingroup, they may either withdraw or engage in compensatory activities designed to reaffirm their social identity as a group member. The authors proposed here that individual differences in identity fusion (an index of familial orientation toward the group) would moderate the tendency for people to display such compensatory activity. Consistent with this reasoning, the results of four experiments showed that irrevocable ostracism increased endorsement of extreme, pro-group actions (fighting and dying for the ingroup) among fused persons but not among nonfused persons. This effect emerged when an outgroup ostracized fused individuals due either to their nationality (Experiment 1) or their personal preferences (Experiment 2). Similarly, ostracism by the ingroup amplified the tendency for fused persons to both endorse extreme pro-group actions, refuse to leave the group (Experiment 3), and donate money to an ingroup member (Experiment 4). Finally, compensatory activities emerged even when ostracism was based on being "too good" for the group, suggesting that a desire for self-enhancement does not mediate such activities (Experiment 4). PMID- 22045778 TI - Changes in mouse liver protein glutathionylation after acetaminophen exposure. AB - The role of protein glutathionylation in acetaminophen (APAP)-induced liver injury was investigated in this study. A single oral gavage dose of 150 or 300 mg/kg APAP in B6C3F1 mice produced increased serum alanine aminotransferase and aspartate aminotransferase levels and liver necrosis in a dose-dependent manner. The ratio of GSH to GSSG was decreased in a dose-dependent manner, suggesting that APAP produced a more oxidizing environment within the liver. Despite the increased oxidation state, the level of global protein glutathionylation was decreased at 1 h and continued to decline through 24 h. Immunohistochemical localization of glutathionylated proteins showed a complex dynamic change in the lobule zonation of glutathionylated proteins. At 1 h after APAP exposure, the level of glutathionylation decreased in the single layer of hepatocytes around the central veins but increased mildly in the remaining centrilobular hepatocytes. This increase correlated with the immunohistochemical localization of APAP covalently bound to protein. Thereafter, the level of glutathionylation decreased dramatically over time in the centrilobular regions with major decreases observed at 6 and 24 h. Despite the overall decreased glutathionylation, a layer of cells lying between the undamaged periportal region and the damaged centrilobular hepatocytes exhibited high levels of glutathionylation at 3 and 6 h in all samples and in some 24-h samples that had milder injury. These temporal and zonal pattern changes in protein glutathionylation after APAP exposure indicate that protein glutathionylation may play a role in protein homeostasis during APAP-induced hepatocellular injury. PMID- 22045781 TI - Piecewise mixed-effects models with skew distributions for evaluating viral load changes: A Bayesian approach. AB - Studies of human immunodeficiency virus dynamics in acquired immuno deficiency syndrome (AIDS) research are very important in evaluating the effectiveness of antiretroviral (ARV) therapies. The potency of ARV agents in AIDS clinical trials can be assessed on the basis of a viral response such as viral decay rate or viral load change in plasma. Following ARV treatment, the profile of each subject's viral load tends to follow a 'broken stick'-like dynamic trajectory, indicating multiple phases of decline and increase in viral loads. Such multiple phases (change-points) can be described by a random change-point model with random subject-specific parameters. One usually assumes a normal distribution for model error. However, this assumption may be unrealistic, obscuring important features of within- and among-subject variations. In this article, we propose piecewise linear mixed-effects models with skew-elliptical distributions to describe the time trend of a response variable under a Bayesian framework. This methodology can be widely applied to real problems for longitudinal studies. A real data analysis, using viral load data from an AIDS study, is carried out to illustrate the proposed method by comparing various candidate models. Biologically important findings are reported, and these findings also suggest that it is very important to assume a model with skew distribution in order to achieve reliable results, in particular, when the data exhibit skewness. PMID- 22045782 TI - Exploring the effects of dance-based therapy on balance and mobility in older adults. AB - Balance and mobility are a common concern among older adults. This pilot randomized controlled study examines the effect of dance-based therapy to increase balance and mobility in 27 participants with mean age 85 years (+/-7.5) from a single aging-in-place facility in the Midwest. Multidirectional reach, velocity, step length differential, and a Functional Ambulation Profile were measured before and after 18 sessions of low-impact dance-based therapy. Although a Wilcoxon rank sum test showed no significance, effect size analyses suggest that dance-based therapy was mildly or moderately effective in several components of balance and mobility. Additional research is needed with a full-scale trial. PMID- 22045783 TI - Ecological risk factors of childhood obesity in Korean elementary school students. AB - The purpose of this study was to examine ecological correlates of obesity among Korean children. Cross-sectional data, including measurements of height and weight, were collected by questionnaire from 1,644 children in the fifth and sixth grades. A multiple logistic regression model incorporating individual- and school-level variables determined factors of childhood obesity. Intrapersonal factors associated with obesity included gender, computer use, and dissatisfaction with body image; significant interpersonal factors included low level of the father's education and encouragement to engage in physical activity. School-level factors that were significant predictors included location in Gyeonggi province, having two or more school exercise facilities, physical education classes of 2 hr per week, higher fat content of school lunch, and higher number of classes in the school. The findings indicate that multifaceted, multilevel prevention strategies to manage and prevent childhood obesity should include behavioral modification, familial support, and improvement of school environments. PMID- 22045785 TI - The European Respiratory Journal makes COPD a priority. PMID- 22045786 TI - Idiopathic pulmonary fibrosis trials: recommendations for the jury. PMID- 22045784 TI - Primary vitreoretinal lymphoma: a report from an International Primary Central Nervous System Lymphoma Collaborative Group symposium. AB - Primary vitreoretinal lymphoma (PVRL), also known as primary intraocular lymphoma, is a rare malignancy typically classified as a diffuse large B-cell lymphoma and most frequently develops in elderly populations. PVRL commonly masquerades as posterior uveitis and has a unique tropism for the retina and central nervous system (CNS). Over 15% of primary CNS lymphoma patients develop intraocular lymphoma, usually occurring in the retina and/or vitreous. Conversely, 65%-90% of PVRL patients develop CNS lymphoma. Consequently, PVRL is often fatal because of ultimate CNS association. Current PVRL animal models are limited and require further development. Typical clinical findings include vitreous cellular infiltration (lymphoma and inflammatory cells) and subretinal tumor infiltration as determined using dilated fundoscopy, fluorescent angiography, and optical coherent tomography. Currently, PVRL is most often diagnosed using both histology to identify lymphoma cells in the vitreous or retina and immunohistochemistry to indicate monoclonality. Additional adjuncts in diagnosing PVRL exist, including elevation of interleukin-10 levels in ocular fluids and detection of Ig(H) or T-cell receptor gene rearrangements in malignant cells. The optimal therapy for PVRL is not defined and requires the combined effort of oncologists and ophthalmologists. PVRL is sensitive to radiation therapy and exhibits high responsiveness to intravitreal methotrexate or rituximab. Although systemic chemotherapy alone can result in high response rates in patients with PVRL, there is a high relapse rate. Because of the disease rarity, international, multicenter, collaborative efforts are required to better understand the biology and pathogenesis of PVRL as well as to define both diagnostic markers and optimal therapies. PMID- 22045787 TI - Determinants of success. AB - In chronic obstructive pulmonary disease (COPD) patients, pulmonary rehabilitation is a nonpharmacological intervention aimed at improving physical exercise tolerance, dyspnoea and perceived quality of life. However, identifying predictors of clinical response and which patients achieve benefit remains a difficult question to answer with no conclusive data available. Baseline characteristics of COPD patients, such as degree of breathlessness, body weight and arterial partial pressure of oxygen, generally appear to be too direct to have a correlation with improvement of post-rehabilitation outcomes. Furthermore, some additional benefits of patients treated with rehabilitation are simply not detected by usual measures (social interaction, sleep quality and confidence). Although there are some data suggesting that some medical conditions frequently associated with COPD (osteoporosis, metabolic syndrome and heart diseases) may negatively influence rehabilitation outcomes, at present the evidence is contradictory. PMID- 22045788 TI - Saliva cotinine levels in users of electronic cigarettes. PMID- 22045789 TI - TB and M/XDR-TB infection control in European TB reference centres: the Achilles' heel? PMID- 22045790 TI - Effects of distance to treatment centre and case load upon tuberculosis treatment completion. PMID- 22045791 TI - Tuberculosis-specific T-cell response after recent treatment and remote cure. PMID- 22045792 TI - Tracheal granuloma pyogenicum with erlotinib treatment for lung cancer. PMID- 22045793 TI - Atypical pulmonary carcinoid tumour in a 28-year-old nonsmoker with Prader-Willi syndrome. PMID- 22045794 TI - Clinical features of central airway involvement in autoimmune pancreatitis. PMID- 22045795 TI - Interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis infection. PMID- 22045797 TI - Increase in walk distance is not enough evidence to add a walk to the 6-minute walk test. PMID- 22045799 TI - Killer weekends: can we do something? PMID- 22045800 TI - Use of the asthma control questionnaire by the asthma clinical research network. PMID- 22045803 TI - Regulatory monitoring is not an intervention; it is merely information. PMID- 22045804 TI - Pediatric drug-trial recruitment: an institutional review board perspective. PMID- 22045805 TI - The economic impact of state cigarette taxes and smoke-free air policies on convenience stores. AB - OBJECTIVES: To investigate whether increasing state cigarette taxes and/or enacting stronger smoke-free air (SFA) policies have negative impact on convenience store density in a state, a proxy that is determined by store openings and closings, which reflects store profits. METHODS: State-level business count estimates for convenience stores for 50 states and District of Columbia from 1997 to 2009 were analysed using two-way fixed effects regression techniques that control for state-specific and year-specific determinants of convenience store density. The impact of tax and SFA policies was examined using a quasi-experimental research design that exploits changes in cigarette taxes and SFA policies within a state over time. RESULTS: Taxes are found to be uncorrelated with the density of combined convenience stores and gas stations in a state. Taxes are positively correlated with the density of convenience stores; however, the magnitude of this correlation is small, with a 10% increase in state cigarette taxes associated with a 0.19% (p<0.05) increase in the number of convenience stores per million people in a state. State-level SFA policies do not correlate with convenience store density in a state, regardless whether gas stations were included. These results are robust across different model specifications. In addition, they are robust with regard to the inclusion/exclusion of other state-level tobacco control measures and gasoline prices. CONCLUSIONS: Contrary to tobacco industry and related organisations' claims, higher cigarette taxes and stronger SFA policies do not negatively affect convenience stores. PMID- 22045806 TI - Pathway profiling in Mycobacterium tuberculosis: elucidation of cholesterol derived catabolite and enzymes that catalyze its metabolism. AB - Mycobacterium tuberculosis, the bacterium that causes tuberculosis, imports and metabolizes host cholesterol during infection. This ability is important in the chronic phase of infection. Here we investigate the role of the intracellular growth operon (igr), which has previously been identified as having a cholesterol sensitive phenotype in vitro and which is important for intracellular growth of the mycobacteria. We have employed isotopically labeled low density lipoproteins containing either [1,7,15,22,26-(14)C]cholesterol or [1,7,15,22,26 (13)C]cholesterol and high resolution LC/MS as tools to profile the cholesterol derived metabolome of an igr operon-disrupted mutant (Deltaigr) of M. tuberculosis. A partially metabolized cholesterol species accumulated in the Deltaigr knock-out strain that was absent in the complemented and parental wild type strains. Structural elucidation by multidimensional 1H and 13C NMR spectroscopy revealed the accumulated metabolite to be methyl 1beta-(2' propanoate)-3aalpha-H-4alpha-(3'-propanoic acid)-7abeta-methylhexahydro-5 indanone. Heterologously expressed and purified FadE28-FadE29, an acyl-CoA dehydrogenase encoded by the igr operon, catalyzes the dehydrogenation of 2' propanoyl-CoA ester side chains in substrates with structures analogous to the characterized metabolite. Based on the structure of the isolated metabolite, enzyme activity, and bioinformatic annotations, we assign the primary function of the igr operon to be degradation of the 2'-propanoate side chain. Therefore, the igr operon is necessary to completely metabolize the side chain of cholesterol metabolites. PMID- 22045807 TI - Mammalian target of rapamycin complex 2 (mTORC2) negatively regulates Toll-like receptor 4-mediated inflammatory response via FoxO1. AB - Activation of the PI3K pathway plays a pivotal role in regulating the inflammatory response. The loss of mTORC2 has been shown to abrogate the activation of Akt, a critical downstream component of PI3K signaling. However, the biological importance of mTORC2 in innate immunity is currently unknown. Here we demonstrate that rictor, a key component of mTORC2, plays a critical role in controlling the innate inflammatory response via its ability to regulate FoxO1. Upon LPS stimulation, both rictor-deficient mouse embryonic fibroblasts (MEFs) and rictor knockdown dendritic cells exhibited a hyperinflammatory phenotype. The hyperinflammatory phenotype was due to a defective Akt signaling axis, because both rictor-deficient MEFs and rictor knockdown dendritic cells exhibited attenuated Akt phosphorylation and kinase activity. Analysis of downstream Akt targets revealed that phosphorylation of FoxO1 was impaired in rictor-deficient cells, resulting in elevated nuclear FoxO1 levels and diminished nuclear export of FoxO1 upon LPS stimulation. Knockdown of FoxO1 attenuated the hyperinflammatory phenotype exhibited by rictor-deficient MEFs. Moreover, FoxO1 deletion in dendritic cells attenuated the capacity of LPS to induce inflammatory cytokine expression. These findings identify a novel signaling pathway by which mTORC2 regulates the TLR-mediated inflammatory response through its ability to regulate FoxO1. PMID- 22045808 TI - Mimivirus collagen is modified by bifunctional lysyl hydroxylase and glycosyltransferase enzyme. AB - Collagens, the most abundant proteins in animals, are modified by hydroxylation of proline and lysine residues and by glycosylation of hydroxylysine. Dedicated prolyl hydroxylase, lysyl hydroxylase, and collagen glycosyltransferase enzymes localized in the endoplasmic reticulum mediate these modifications prior to the formation of the collagen triple helix. Whereas collagen-like proteins have been described in some fungi, bacteria, and viruses, the post-translational machinery modifying collagens has never been described outside of animals. We demonstrate that the L230 open reading frame of the giant virus Acanthamoeba polyphaga mimivirus encodes an enzyme that has distinct lysyl hydroxylase and collagen glycosyltransferase domains. We show that mimivirus L230 is capable of hydroxylating lysine and glycosylating the resulting hydroxylysine residues in a native mimivirus collagen acceptor substrate. Whereas in animals from sponges to humans the transfer of galactose to hydroxylysine in collagen is conserved, the mimivirus L230 enzyme transfers glucose to hydroxylysine, thereby defining a novel type of collagen glycosylation in nature. The presence of hydroxylysine in mimivirus proteins was confirmed by amino acid analysis of mimivirus recovered from A. polyphaga cultures. This work shows for the first time that collagen post translational modifications are not confined to the domains of life. The utilization of glucose instead of the galactose found throughout animals as well as a bifunctional enzyme rather than two separate enzymes may represent a parallel evolutionary track in collagen biology. These results suggest that giant viruses may have contributed to the evolution of collagen biology. PMID- 22045809 TI - Everything is connected to everything else. PMID- 22045810 TI - Protein-tyrosine phosphatase 1B modulates early endosome fusion and trafficking of Met and epidermal growth factor receptors. AB - The endoplasmic reticulum-localized non-receptor protein-tyrosine phosphatase 1B (PTP1B) is associated with oncogenic, metabolic, and cytokine-related signaling and functionally targets multiple receptor tyrosine kinases (RTKs) for dephosphorylation. Loss of PTP1B activity leads to enhanced ligand-dependent biological activity of the Met RTK among others. Here, we demonstrate that knockdown of PTP1B or expression of a PTP1B trapping aspartic acid-to-alanine substitution (D/A) mutant delayed ligand-induced degradation of the Met and EGF RTKs. Loss of PTP1B function abrogated trafficking of Met and EGF receptor to Rab5- and phosphatidylinositol 3-phosphate (Pl3P)-positive early endosomes and subsequent trafficking through the degradative pathway. Under these conditions, internalization of the Met and EGF receptors was unaltered, suggesting a block at the level of early endosome formation. We show that the N-ethylmaleimide sensitive factor (NSF), an essential component of the vesicle fusion machinery, was hyperphosphorylated in PTP1B knockdown or PTP1B D/A-expressing cells and was a target for PTP1B. NSF knockdown phenocopied PTP1B knockdown, demonstrating a mechanism through which PTP1B regulates endocytic trafficking. Finally, we show that PTP1B dephosphorylated NSF and that this interaction was required for physiological RTK trafficking and appropriate attenuation of downstream signaling. PMID- 22045811 TI - Degradation of p21Cip1 through anaphase-promoting complex/cyclosome and its activator Cdc20 (APC/CCdc20) ubiquitin ligase complex-mediated ubiquitylation is inhibited by cyclin-dependent kinase 2 in cardiomyocytes. AB - Cyclin-dependent kinase inhibitor p21Cip1 plays a crucial role in regulating cell cycle arrest and differentiation. It is known that p21Cip1 increases during terminal differentiation of cardiomyocytes, but its expression control and biological roles are not fully understood. Here, we show that the p21Cip1 protein is stabilized in cardiomyocytes after mitogenic stimulation, due to its increased CDK2 binding and inhibition of ubiquitylation. The APC/CCdc20 complex is shown to be an E3 ligase mediating ubiquitylation of p21Cip1 at the N terminus. CDK2, but not CDC2, suppressed the interaction of p21Cip1 with Cdc20, thereby leading to inhibition of anaphase-promoting complex/cyclosome and its activator Cdc20 (APC/CCdc20)-mediated p21Cip1 ubiquitylation. It was further demonstrated that p21Cip1 accumulation caused G2 arrest of cardiomyocytes that were forced to re enter the cell cycle. Taken together, these data show that the stability of the p21Cip1 protein is actively regulated in terminally differentiated cardiomyocytes and plays a role in inhibiting their uncontrolled cell cycle progression. Our study provides a novel insight on the control of p21Cip1 by ubiquitin-mediated degradation and its implication in cell cycle arrest in terminal differentiation. PMID- 22045812 TI - Identification of a new fatty acid synthesis-transport machinery at the peroxisomal membrane. AB - The neurodegenerative disease X-linked adrenoleukodystrophy (X-ALD) is characterized by the abnormal accumulation of very long chain fatty acids. Mutations in the gene encoding the peroxisomal ATP-binding cassette half transporter, adrenoleukodystrophy protein (ALDP), are the primary cause of X-ALD. To gain a better understanding of ALDP dysfunction, we searched for interaction partners of ALDP and identified binary interactions to proteins with functions in fatty acid synthesis (ACLY, FASN, and ACC) and activation (FATP4), constituting a thus far unknown fatty acid synthesis-transport machinery at the cytoplasmic side of the peroxisomal membrane. This machinery adds to the knowledge of the complex mechanisms of peroxisomal fatty acid metabolism at a molecular level and elucidates potential epigenetic mechanisms as regulatory processes in the pathogenesis and thus the clinical course of X-ALD. PMID- 22045813 TI - miR-183-96-182 cluster is overexpressed in prostate tissue and regulates zinc homeostasis in prostate cells. AB - Decreased zinc levels are a hallmark of prostate cancer tumors as zinc uniquely concentrates in healthy prostate tissue. Increased dietary zinc correlates with decreased risk of advanced prostate cancer and decreased mortality from prostate cancer. The mechanisms of prostatic zinc homeostasis are not known. Lower zinc levels in the tumor are correlated directly with decreased expression of the zinc transporter hZIP1. We report identification of a microRNA cluster that regulates multiple zinc transporters, including hZIP1. Screening in laser capture microdissected prostate cancer tumors identified miR-182 as a potential regulator of hZIP1. Regulation of hZIP1 by miR-182 via two binding sites was confirmed in primary prostate cell cultures. miR-96 and miR-183 are expressed as a cluster with miR-182 and share similar sequences. Array profiling of tissue showed that miR-183, -96, and -182 are higher in prostate cancer tissue compared with normal prostate. Overexpression of the entire miR-183-96-182 cluster suppressed five additional zinc transporters. Overexpression of miR-183, -96, and -182 individually or as a cluster diminished labile zinc pools and reduced zinc uptake, demonstrating this miR cluster as a regulator of zinc homeostasis. We observed regulation of zinc homeostasis by this cluster in prostate cells and HEK 293 cells, suggesting a universal mechanism that is not prostate-specific. To our knowledge, this is the first report of a miR cluster targeting a family of metal transport proteins. Individually or as a cluster, miR-183, -96, and -182 are overexpressed in other cancers too, implicating this miR cluster in carcinogenesis. PMID- 22045814 TI - Ubiquitin ligase Ufd2 is required for efficient degradation of Mps1 kinase. AB - Ufd2 is a U-box-containing ubiquitylation enzyme that promotes ubiquitin chain assembly on substrates. The physiological function of Ufd2 remains poorly understood. Here, we show that ubiquitylation and degradation of the cell cycle kinase Mps1, a known target of the anaphase-promoting complex E3, require Ufd2 enzyme. Yeast cells lacking UFD2 exhibit altered chromosome stability and several spindle-related phenotypes, expanding the biological function of Ufd2. We demonstrate that Ufd2-mediated Mps1 degradation is conserved in humans. Our results underscore the significance of Ufd2 in proteolysis and further suggest that Ufd2-like enzymes regulate far more substrates than previously envisioned. PMID- 22045815 TI - Novel mechanism of RNA repair by RtcB via sequential 2',3'-cyclic phosphodiesterase and 3'-Phosphate/5'-hydroxyl ligation reactions. AB - RtcB enzymes are a newly discovered family of RNA ligases, implicated in tRNA splicing and other RNA repair reactions, that seal broken RNAs with 2',3'-cyclic phosphate and 5'-OH ends. Parsimony and energetics would suggest a one-step mechanism for RtcB sealing via attack by the O5' nucleophile on the cyclic phosphate, with expulsion of the ribose O2' and generation of a 3',5' phosphodiester at the splice junction. Yet we find that RtcB violates Occam's razor, insofar as (i) it is adept at ligating 3'-monophosphate and 5'-OH ends; (ii) it has an intrinsic 2',3'-cyclic phosphodiesterase activity. The 2',3' cyclic phosphodiesterase and ligase reactions both require manganese and are abolished by mutation of the RtcB active site. Thus, RtcB executes a unique two step pathway of strand joining whereby the 2',3'-cyclic phosphodiester end is hydrolyzed to a 3'-monophosphate, which is then linked to the 5'-OH end to form the splice junction. The energy for the 3'-phosphate ligase activity is provided by GTP, which reacts with RtcB in the presence of manganese to form a covalent RtcB-guanylate adduct. This adduct is sensitive to acid and hydroxylamine but resistant to alkali, consistent with a phosphoramidate bond. PMID- 22045816 TI - Lung cancer screening with low-dose helical CT: results from the National Lung Screening Trial (NLST). PMID- 22045817 TI - Some clarity in the management of DCIS in breast cancer screening. PMID- 22045818 TI - Screening for cardiovascular disease using age alone: reflections on a paper peer reviewed as both 'radical' and 'unsurprising'. PMID- 22045819 TI - Causes of delay in referral of patients with phenylketonuria to a specialized reference centre in Mexico. AB - OBJECTIVE: To expose causes leading to the delayed arrival of phenylketonuria (PKU) patients at a governmental reference centre (RC), and to describe their clinical characteristics. Material and methods PKU files registered during the past 18 years at the National Institute of Pediatrics in Mexico City were evaluated. Patients were classified into two groups according to their age at arrival: Group I (early reference), patients arriving during the first month of life; and Group II (late reference), those who arrived after thirty days of age. Time and causes of delay were documented. RESULTS: Of 57 recorded files, 10 were classified in Group I and 47 in Group II. Causes leading to the late arrival of Group II patients were absence of routine newborn screening (NBS), PKU not included in the routine NBS, sampling after the recommended age, false negative result, results without interpretation and/or instructions to follow, delayed notification of results, poor medical criteria of attending physician, difficulties in obtaining confirmatory tests, and administrative failures. CONCLUSION: The main cause of late referral of PKU patients was the absence of PKU testing. As a developing country, Mexico still faces challenges in the proper functioning and expansion of the NBS programme. Most PKU patients arrived at the RC late, presenting with varying degrees of the clinical spectrum. Incorporating PKU testing into the already established Mexican NBS system and adding quality indicators to guarantee proper operation in all NBS phases is necessary to achieve the goal of identifying, referring, diagnosing, and treating patients promptly. PMID- 22045820 TI - Direct mailing of faecal occult blood tests for colorectal cancer screening: a randomized population study from Central Italy. AB - BACKGROUND: Sending faecal occult blood tests (FOBT) by mail has been proposed both as a method to increase participation and a way to reduce staff costs in colorectal cancer screening. METHODS: Two multicentre randomized controlled trials (ISRCTN10351276) were performed: one randomly assigned 3196 individuals who had previously participated in colorectal screening to receive a FOBT kit at home or a standard invitation; in the second, 4219 people aged 50-69 years who did not respond to a screening invitation were either sent a FOBT or a standard recall letter. The cost per returned kit was calculated in each arm. RESULTS: Participation was higher with direct FOBT mailing in both trials: relative risk 1.11 (95% CI 1.06-1.17) and 1.36 (95% CI 1.16-1.60) for previous responders and non-responders, respectively. The cost per returned kit for previous responders ranged from 4.24? to 16.10?, and from 3.29? to 7.36? with FOBT mailing and standard invitation, respectively, not including staff costs; for non-responders it ranged from 17.13? to 46.80?, and from 7.36? to 18.30? with FOBT mailing and standard recall, respectively. CONCLUSIONS: The FOBT mailing strategy modestly increased participation. This method can be used on a population of previous responders to reduce personnel costs and workload. When used as a reminder to non responders, this method increases costs. PMID- 22045821 TI - Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting. AB - OBJECTIVE: Quantitative information on adverse reactions associated with colorectal cancer (CRC) screening tests is useful to estimate the balance between benefit and risk in different strategies. SETTING: Six Italian screening centres. METHODS: Thirty-day active follow-up (interview about side-effects and acceptability of the screening procedure and review of hospital admissions) among average-risk people undergoing flexible sigmoidoscopy (FS), total colonoscopy (TC), fecal immunochemical test (FIT) in a multicentre randomized trial of CRC screening. Multivariable logistic models were used to assess determinants of completion rate and self-reported pain. RESULTS: The attendance rate following the first invitation and mail reminder was 28.2% (1696/6018) in the FS and 23.0% (1382/6021) in the TC arm. Response rate to the 30-day follow-up questionnaire was 88.6% (1502/1696) among people undergoing FS, and 86.7% (1198/1382) among those undergoing TC. The proportion of people complaining of serious reactions following bowel preparation (odds ratio [OR], 5.17; 95% confidence interval [CI] 3.70-7.24) or reporting severe pain immediately after the exam (OR, 1.86; 95% CI 1.47-2.34) was higher for TC than for FS. The most common post-procedural complaints were abdominal distension and pain. People mentioning pain or bowel distension following preparation were more likely to report severe pain both after FS (OR, 2.13; 95% CI 1.52-2.97) and TC (OR: 2.03; 95% CI 1.41-2.90). The 30 day hospitalization rate was similar after FS, TC and FIT. CONCLUSIONS: Screenees reported higher pain levels after TC than FS. The proportion of people complaining of severe side effects after discharge was similar. Bowel preparation was poorly tolerated by people undergoing TC. Subjects' reactions to the bowel preparation was predictive of post-procedural discomfort. A commitment of at least 48 hours was required of people undergoing TC, compared with 3-4 for FS. PMID- 22045822 TI - Factors affecting compliance in faecal occult blood testing: a cluster randomized study of the faecal immunochemical test versus the guaiac faecal occult test. AB - OBJECTIVE: To compare the uptake of faecal immunochemical occult blood test (FIT) with guaiac faecal occult blood test (gFOBT) in a screening programme, with specific attention to the demographic and socioeconomic factors that might affect test uptake. SETTING: The Clalit Health Service screening programme, Israel. METHODS: Average-risk individuals aged 50-75 years were randomized into a FIT arm or gFOBT arm using a programme based on the socioeconomic status (SES) of their primary care clinics. G-FOBT was performed with Hemoccult SENSATM (3 evacuations) and FIT with the OC- MICRO(TM) (3 evacuations, refrigerating mandated). The GLIMMIX model was used. RESULTS: There were 5,464 and 10,668 eligible participants in the FIT and gFOBT arms respectively. Compliance in taking the kits was better (but not statistically significantly better) with gFOBT (37.8% vs. 29.3%; odds ratio [OR] 1.43 [95% CI 0.73-2.80]; P = 0.227). Kit return was higher in the FIT arm (65.0% vs. 78.9%; OR 0.45 [95% CI 0.24-0.83], P = 0.021). Overall test uptake was affected by age, gender, being immigrant and SES (determined by whether or not the participant paid national insurance tax, and the SES of the primary care clinic). The overall uptake of gFOBT and FIT was comparable (OR 0.996 [95% CI 0.46-2.17], P = 0.99). CONCLUSIONS: Overall compliance for test uptake was comparable between the two methods despite the more demanding procedure in the FIT arm. Sociodemographic parameters were the major determinants of compliance. An educational programme, with emphasis on the sociodemographic characteristics of the target population, should be instigated. PMID- 22045823 TI - Minor influence of self-selection bias on the effectiveness of breast cancer screening in case-control studies in the Netherlands. AB - BACKGROUND: Self-selection bias is considered to be a problem when evaluating the effectiveness of breast cancer service screening in case-control studies. OBJECTIVE: Using the incidence-based mortality method (IBM), a correction factor for the potential influence of self-selection can be derived from a group of non screened women and a group of not-invited women. METHODS: Breast cancer patients, diagnosed in 1990-1995 and between the ages of 50 to 70, were selected from the Netherlands Cancer Registry and five screening regions in the Netherlands. Person years were calculated for non-screened and not-invited women by using population data available on the number of women invited, the number of women screened and the total population. Incidence-based breast cancer mortality rates according to screening status were calculated for the five screening regions. RESULTS: Between 1990-1995, 15,541 patients were diagnosed with breast cancer. An analysis of ten year follow-up after diagnosis resulted in 3903 breast cancer deaths, of which 2631 were not-invited and 345 were non-screened. Poisson regression analysis showed heterogeneity between the regions with a range of IBM ratios from 0.64 (95% CI: 0.46-0.90) to 1.08 (95% CI: 0.82-1.43). CONCLUSIONS: Heterogeneity between the regions stresses the importance of a country- and/or region- specific estimate of self-selection. Adjusting for self-selection bias in the regional case-control studies would not change the breast cancer mortality reduction in three regions and would result in an even larger effect in two regions. Looking at the range of IBM ratios the overall influence of self-selection in the Netherlands is minor. PMID- 22045824 TI - Evaluation of the nationwide cervical screening programme in Thailand: a case control study. AB - OBJECTIVES: To evaluate the effectiveness of the Pap smear screening programme in Thailand in the prevention of invasive cervical cancer. SETTING: Four tertiary hospitals, in two provinces of north-east Thailand. METHODS: A hospital-based case-control study of women aged 30-64, who were resident in north-east Thailand. A total of 130 women with a diagnosis of invasive cervical cancer were compared with two groups of controls: a) hospital controls, b) hospital patient companions. Information on risk factors for cervical cancer and history of screening by cytology (Pap smear) were collected using a structured interview. RESULTS: Eighty percent of control subjects reported having had a Pap test in the past, and some two-thirds within the three years before interview. There was a significant protective effect for multiple (6+) previous screening tests as reported by 20% of controls. When women who had tests less than six months prior to the study were excluded, there was a strong, significant protective effect of the number of tests (for 1-5 tests: OR = 0.45 95% CI = 0.25 to 0.84, and for 6+ tests: OR = 0.29 95% CI = 0.11 to 0.82). Tests carried out 1-2 years and 3+ years before diagnosis were associated with an OR of 0.27 (95% CI = 0.13-0.56) and 0.42 (95% CI = 0.20-0.88), respectively. CONCLUSIONS: The cervical screening programme in north-east Thailand has achieved excellent coverage and is preventing cervical cancer. Women who have been screened multiple times are at substantially lower risk than those only screened a few times suggesting that the quality of the screening could be improved. PMID- 22045825 TI - Longitudinal predictors of adherence to annual follow-up in a lung cancer screening programme. AB - OBJECTIVE: To examine rates and factors associated with adherence to annual repeat lung cancer screening in two cohorts. Participants and methods The self pay cohort (n = 2083) was individuals aged 40 years and older with no prior cancer and a smoking history. Participants had to obtain a prescription from their doctor for the low dose, computerized tomography scan (CT), and were responsible for payment of $300 as these CT scans are not typically covered by insurance. The no-pay cohort (n = 1304) was individuals aged 60 and older with a smoking history, and no prior cancer. The initial and one year repeat CT were provided free of charge. Rates of adherence for each cohort were analyzed by demographic variables, smoking history, family history of lung cancer, smoking status (former/current), perceived risk and worry of getting lung cancer and baseline screening CT. RESULTS: Adherence to annual follow-up was lower for the self-pay than for the no-pay cohort (62% vs. 88%). Both the self-pay and no-pay cohorts had higher adherence rates among Caucasians and those who had a college degree. A greater perceived risk of getting lung cancer increased adherence among the self-pay cohort. Non-calcified nodules found on baseline CT increased the adherence for the self-pay cohort, but decreased the adherence for the no-pay cohort. CONCLUSIONS: These findings should be used in developing educational materials and targeted retention strategies to increase adherence with repeat lung cancer screening. PMID- 22045826 TI - Single negative colposcopy: is it enough to rule out high-grade disease? AB - It has been proposed that women who have a negative colposcopic examination or who have no cervical intraepithelial neoplasia (CIN) on colposcopic biopsy can be safely returned to routine screening with the next visit being three or five years later. We present data regarding 551 women who had colposcopy in Wales for a low-grade cytological abnormality and who were followed through Cervical Screening Wales for subsequent CIN. Of 436 women declared CIN free initially, 26 (6.0%) had high-grade CIN diagnosed on follow-up. We suggest that additional screening at an interval of less than three years should be offered to women with a negative colposcopy or a biopsy without CIN. PMID- 22045827 TI - Efficacy and safety of Aethoxysklerol(r) (polidocanol) 0.5%, 1% and 3% in comparison with placebo solution for the treatment of varicose veins of the lower extremities in Chinese patients (ESA-China Study). AB - OBJECTIVES: To assess efficacy and safety of polidocanol (POL) versus placebo in the treatment of C1 and C2 non-saphenous varicose veins in Chinese patients. METHODS: Patients were randomly assigned to POL or placebo. POL 0.5%, 1% and 3% were administered depending on varicose vein type. Response after 12 weeks was defined as Grade 4 or 5 on a digital imaging-based five-point scale (C1 veins) or occlusion and/or absence of reflux >0.5 second (C2 veins). Safety was evaluated with a five-point scale and standard safety assessments. RESULTS: Two hundred and eighty-five patients were treated. POL 0.5%, 1% and 3% were each superior to placebo (P < 0.001); response rates: 87.1% versus 13.6%, 86.4% versus 12.5% and 88.6% versus 4.3%, respectively. Significantly more POL than placebo patients were satisfied/very satisfied with treatment. POL was well tolerated, with mostly symptoms at the injection site reported. CONCLUSIONS: Sclerotherapy with POL 0.5%, 1% and 3% was efficacious and safe in Chinese patients. PMID- 22045828 TI - Cancer incidence in patients with schizophrenia or bipolar disorder: a nationwide population-based study in Taiwan, 1997-2009. AB - BACKGROUND: Both genetic and environmental factors have been reasoned for cancer development in schizophrenia patients. However, the influence of age of onset and duration of schizophrenia on cancer incidence has rarely been emphasized. Besides, bipolar disorder tends to resemble schizophrenia from the perspective of multiple rare mutations. Comparing pattern and risk of cancers between schizophrenia and bipolar patients is illuminating. METHODS: This study used the Taiwan National Health Insurance Database. A total of 71,317 schizophrenia and 20,567 bipolar disorder patients from 1997 to 2009 were enrolled. Both cohorts were followed up for cancer during the same period by record linkage with the cancer certification in Taiwan. Age and gender standardized incidence ratios (SIRs) of overall and site-specific cancers were calculated. RESULTS: The SIR for all cancers was 1.17 for the schizophrenia cohort. Increased cancer risk (SIR: 1.31, 95% CI: 1.17-1.48) was observed in females but not males. For the bipolar disorder cohort, the SIR for all cancers was 1.29, but the excess risk was found in males (SIR: 1.42, 95% CI: 1.14-1.77) and not females. Cancer risk decreases as the duration and age of onset of schizophrenia increases. If schizophrenia is diagnosed before 50, the SIRs for colorectal, breast, cervical, and uterine cancers increase but if diagnosed after 50, the SIRs for all cancers decrease except for breast cancer. In bipolar disorder, the SIRs for all site-specific cancers were insignificant. CONCLUSIONS: Among schizophrenia patients, overall cancer risk varies inversely with age at diagnosis and disease duration. Besides, gender-specific cancer risks differ between schizophrenia and bipolar disorder. PMID- 22045829 TI - Pharmacokinetic-pharmacodynamic assessment of the interrelationships between tesaglitazar exposure and renal function in patients with type 2 diabetes mellitus. AB - The effects of tesaglitazar on renal function (assessed as urinary clearance of 125I-sodium iothalamate or estimated by the modification of diet in renal disease formula) were studied in a 24-week open-label trial in type 2 diabetes mellitus patients randomized to daily doses of either tesaglitazar 2 mg or pioglitazone 45 mg. The aim of the analysis was to develop a population pharmacokinetic pharmacodynamic model that could simultaneously describe the interrelationship between tesaglitazar exposure and reduction in renal function over time in patients with type 2 diabetes mellitus. The pharmacokinetic-pharmacodynamic model could adequately describe the interplay between tesaglitazar and glomerular filtration rate. A one-compartment model in which the apparent clearance was influenced by glomerular filtration rate characterized the pharmacokinetics of tesaglitazar. An indirect-response model was used for the slow time course of change in glomerular filtration rate, which decreased from 100 to 78 mL/min/1.73m(2) after 12 weeks of treatment. All tesaglitazar-treated patients had a reduction in glomerular filtration rate, and available demographic variables could not explain differences in response. Patients treated with an angiotensin converting enzyme inhibitor were more sensitive to tesaglitazar and had larger glomerular filtration rate decrease compared to nontreated patients. Approximately 8 weeks after discontinuing treatment, mean glomerular filtration rate had returned towards baseline. The model and data give valuable insights into the dynamic changes in glomerular filtration rate over time. PMID- 22045830 TI - Enhanced sensitivity to drug-induced QT interval lengthening in patients with heart failure due to left ventricular systolic dysfunction. AB - Patients with heart failure (HF) are at increased risk for drug-induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug-induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillation or flutter requiring conversion to sinus rhythm were enrolled: 6 patients with New York Heart Association class II to III HF (mean ejection fraction [EF], 30% +/- 9%), and 9 controls (mean EF, 53% +/- 6%). Patients received ibutilide 1 mg intravenously. Blood samples and 12-lead electrocardiograms were obtained prior to and during 48 hours postinfusion. Serum ibutilide concentrations at 50% maximum effect on Fridericia-corrected QT (QT(F)) intervals (EC(50)) were determined, and areas under the effect (QT(F) interval vs time) curves (AUECs) were calculated. Ibutilide concentration-QT(F) relationships were best described by a sigmoidal E(max) model with a hypothetical effect compartment. Median [interquartile range] AUEC from 0 to 4 hours was larger in the HF group than in controls (1.86 [1.86-1.93] vs 1.82 [1.81-1.84] s.h; P = .04). Median EC(50) was lower in the HF group (0.48 [0.46-0.49] vs 1.85 [1.10-3.23] MUg/L; P = .008). Sensitivity to drug-induced QT interval lengthening is enhanced in patients with systolic HF, which may contribute to the increased risk of drug-induced TdP. PMID- 22045831 TI - The effects of N-acetylcysteine and deferoxamine on plasma cytokine and oxidative damage parameters in critically ill patients with prolonged hypotension: a randomized controlled trial. AB - Reactive oxygen species and inflammation have been implicated in renal tubule cell injury. However, there is some controversy concerning whether antioxidants might attenuate oxidative damage and inflammation in humans after hypotension in the setting of critical illness. This study was a prospective, randomized, double blinded, placebo-controlled study that included patients with hypotension. Patients were randomized to receive either N-acetylcysteine (NAC; 50 mg/kg by 4 hours followed by 100 mg/kg/d for 48 hours diluted in 5% glucose) and deferoxamine (DFX; at a single dose of 1000 mg diluted in 5% glucose) or placebo. The primary study outcome was the serum levels of markers of oxidative damage and inflammatory response. Secondary outcomes included the incidence of acute renal failure, serum creatinine at hospital discharge, intensive care unit length of stay, and length of hospital stay. Thirty patients were enrolled in the study. The use of NAC plus DFX decreased the oxidative damage parameters but not plasma interleukin-6 levels. In contrast, plasma nitrite levels increased 24 hours after NAC plus DFX administration. On analysis of secondary outcomes, it was observed that creatinine levels at hospital discharge were lower in patients receiving NAC plus DFX when compared with placebo. NAC plus DFX administration was able to decrease plasma markers of oxidative damage and creatinine levels at hospital discharge. PMID- 22045832 TI - Editorial expression of concern. PMID- 22045833 TI - Treatment of osteoarthritis with continuous versus intermittent celecoxib. AB - OBJECTIVE: To determine whether "continuous" celecoxib is more efficacious than "intermittent" use in preventing osteoarthritis (OA) flares of the knee and/or hip. METHODS: A double-blind, randomized, multicenter international study comparing efficacy and safety of continuous (daily) versus intermittent (as required during predefined OA flare) celecoxib 200 mg/day in 858 subjects, aged 18-80 years. The study consisted of 3 periods: (I) screening/washout visit; (II) open-label run-in with celecoxib; and (III) 22-week blinded treatment. Only subjects whose OA flares resolved in Period 2 (without subsequent flare) were randomized. The primary endpoint, number of flares per time of exposure during Period III (number of flares per month), was compared using analysis of variance with treatment as the independent variable. Acetaminophen was available as rescue medication. RESULTS: Of 875 subjects randomized to treatment, 858 subjects received treatment. At randomization > 70% were female; mean age 58.6 years; mean disease duration 6.5 years; total Western Ontario and McMaster Universities Osteoarthritis Index mean score 25.8; ~45% had hypertension; and ~20% were using aspirin (for cardiovascular prophylaxis). Subjects receiving continuous treatment reported 42% fewer OA flares/month than intermittent users (p < 0.0001) or 2.0 fewer OA flares over 22 weeks. Statistical and clinically meaningful benefits in secondary outcomes were also evident with continuous treatment. There were no differences in adverse events (AE) or new-onset/aggravated hypertension. CONCLUSION: Continuous treatment with celecoxib 200 mg/day was significantly more efficacious than intermittent use in preventing OA flares of the hip and knee, without an increase in overall AE, including gastrointestinal disorders and hypertension, during 22 weeks of treatment. ClinicalTrials.gov identifier NCT00139776. PMID- 22045834 TI - Polymorphisms in the interleukin 4, interleukin 13, and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression. AB - OBJECTIVE: Polymorphisms in the genes encoding interleukin 4 (IL4), interleukin 13 (IL13), and their corresponding receptors have been associated with multiple immune-mediated diseases. Our aim was to validate these previous observations in patients with systemic sclerosis (SSc) and scrutinize the effect of the polymorphisms on gene expression in various populations of peripheral blood leukocytes. METHODS: We genotyped a cohort of 2488 patients with SSc and 2246 healthy controls from The Netherlands, Spain, United Kingdom, Italy, Germany, and France. Taqman assays were used to genotype single-nucleotide polymorphisms (SNP) in the following genes: (1) IL4 (-590C>T/rs2243250); (2) IL4 receptor alpha (IL4RA) (Q576R/rs1801275); (3) IL13 (R130Q/rs20541 and -1112C>T/rs1800925); and (4) IL13RA1 (43163G>A/rs6646259). The effect of these polymorphisms on expression of the corresponding genes was assessed using quantitative RT-PCR on RNA derived from peripheral blood B cells, T cells, plasmacytoid dendritic cells, monocytes, and myeloid dendritic cells. We investigated whether these polymorphisms influenced development of pulmonary complications over 15 years in patients with SSc. RESULTS: None of the investigated polymorphisms was associated with SSc or any SSc clinical subtype. We did not observe any effect on transcript levels in the cell subtypes or on development of pulmonary complications. CONCLUSION: Our data showed that polymorphisms in IL4, IL13, and their receptors do not play a role in SSc and do not influence the expression of their corresponding transcript in peripheral blood cells. PMID- 22045835 TI - Effectiveness of statins on total cholesterol and cardiovascular disease and all cause mortality in osteoarthritis and rheumatoid arthritis. AB - OBJECTIVE: There is increasing prevalence of hypercholesterolemia among patients with osteoarthritis (OA) and rheumatoid arthritis (RA). We examined the effectiveness of statins on total cholesterol (TC), cardiovascular (CV) morbidity, and mortality in patients with OA or RA. METHODS: A population-based cohort study was done using a record-linkage database in Tayside, Scotland. In total, 2024 OA or RA patients who had at least 2 separate TC measurements between 1993 and 2007 were studied. They were categorized into statin-exposed and statin unexposed groups according to statin use status during followup. The main outcomes were TC concentration change from baseline, CV events, and all-cause mortality during the followup. Multivariate Cox regression models with a time dependent variable for statins were employed to assess the risk of outcomes. RESULTS: Statin-associated TC concentrations in OA decreased by 15% in patients without CV disease (primary prevention, n = 1269) and 7% in patients with CV disease (secondary prevention, n = 247) from baseline of 5.30 mmol/l and 4.54 mmol/l, respectively. Correspondingly, in RA TC was reduced by 16% (n = 430) and 15% (n = 78) with baselines of 5.54 mmol/l and 4.95 mmol/l. In primary prevention, statins were associated with reduced CV events and all-cause mortality in RA patients [adjusted HR 0.45 (95% CI 0.20-0.98) and 0.43 (95% CI 0.20-0.92), respectively] and all-cause mortality in OA patients [adjusted HR 0.43 (95% CI 0.25-0.72)]. Statins were not associated with reduced risk of CV events or all-cause mortality in the secondary prevention of RA or OA patients [adjusted HR 0.68 (95% CI 0.30-1.54) and 0.52 (95% CI 0.20-1.34) for OA patients, and HR 0.58 (95% CI 0.07-4.79) and 0.79 (95% CI 0.18-3.53) for RA patients]. CONCLUSION: Statins reduced TC concentrations between 7% and 16% in patients with OA or RA. Statins were associated with reduced CV events and mortality in RA and mortality in OA in primary prevention. PMID- 22045836 TI - Health-related quality of life outcomes of adalimumab for patients with early rheumatoid arthritis: results from a randomized multicenter study. AB - OBJECTIVE: Rheumatoid arthritis (RA) is associated with significant impairments in health-related quality of life (HRQOL). We evaluated patient-reported outcomes including HRQOL outcomes following adalimumab plus methotrexate (MTX) therapy in patients with early RA. METHODS: PREMIER was a phase III, multicenter, randomized, double-blind, active-comparator clinical trial in early RA. Patients aged >= 18 years were randomly assigned to receive adalimumab 40 mg every other week (eow) plus weekly MTX, weekly MTX, or adalimumab 40 mg eow for 104 weeks. American College of Rheumatology (ACR) criteria were used to evaluate clinical efficacy and response. Outcomes were assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI), Short-Form 36 Health Survey (SF-36), Short-Form 6 Dimension (SF-6D), visual analog scale (VAS) assessments of global disease activity (patient's global assessment; PtGA) and pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Health Utility Index Mark 3 (HUI-3). RESULTS: Of 799 patients enrolled, 268 received adalimumab plus MTX, 257 received MTX monotherapy, and 274 received adalimumab monotherapy. Patients treated with adalimumab plus MTX demonstrated significant baseline to Week 104 improvements in HAQ-DI (p < 0.0001), SF-36 Physical Component Summary (p < 0.0001), 4 SF-36 domains [physical function (p < 0.0001), bodily pain (p <0.0001), vitality (p = 0.0139), role limitations-physical (p = 0.0005)], SF-6D (p = 0.0152), VAS-PtGA (p < 0.0001), VAS-pain (p < 0.0001), FACIT-F (p < 0.0001), and HUI-3 (p = 0.0034) scores versus patients treated with MTX monotherapy. Both SF-6D and HUI-3 were found to be sensitive preference-based measures for assessing the effects of treatment on multidimensional function. No clinically meaningful differences between adalimumab and MTX monotherapy groups were observed for most measures. For each measure, there was significant association between HRQOL improvement and ACR clinical response. CONCLUSION: Adalimumab plus MTX significantly improved physical functioning and HRQOL in patients with early RA over 2 years of treatment. (ClinicalTrials.gov identifier NCT00195663). PMID- 22045837 TI - Hand joint space narrowing and osteophytes are associated with magnetic resonance imaging-defined knee cartilage thickness and radiographic knee osteoarthritis: data from the Osteoarthritis Initiative. AB - OBJECTIVE: To evaluate whether features of radiographic hand osteoarthritis (OA) are associated with quantitative magnetic resonance imaging (MRI)-defined knee cartilage thickness, radiographic knee OA, and 1-year structural progression. METHODS: A total of 765 participants in Osteoarthritis Initiative (OAI; 455 women, mean age 62.5 yrs, SD 9.4) obtained hand radiographs (at baseline), knee radiographs (baseline and Year 1), and knee MRI (baseline and Year 1). Hand radiographs were scored for presence of osteophytes and joint space narrowing (JSN). Knee radiographs were scored according to the Kellgren-Lawrence (KL) scale. Cartilage thickness in the medial and lateral femorotibial compartments was measured quantitatively from coronal FLASHwe images. We examined the cross sectional and longitudinal associations between features of hand OA (total osteophyte and JSN scores) and knee cartilage thickness, 1-year knee cartilage thinning (above smallest detectable change), presence of knee OA (KL grade >= 3), and progression of knee OA (KL change >= 1) by linear and logistic regression. Both hand OA features were included in a multivariate model (if p <= 0.25) adjusted for age, sex, and body mass index (BMI). RESULTS: Hand JSN was associated with reduced knee cartilage thickness (beta = -0.02, 95% CI -0.03, 0.01) in the medial femorotibial compartment, while hand osteophytes were associated with the presence of radiographic knee OA (OR 1.10, 95% CI 1.03-1.18; multivariate models) with both hand OA features as independent variables adjusted for age, sex, and BMI). Radiographic features of hand OA were not associated with 1-year cartilage thinning or radiographic knee OA progression. CONCLUSION: Our results support a systemic OA susceptibility and possibly different mechanisms for osteophyte formation and cartilage thinning. PMID- 22045838 TI - Effects of smoking on disease activity and radiographic progression in early rheumatoid arthritis. AB - OBJECTIVE: To analyze the effects of cigarette smoking on disease activity and radiographic damage in patients with early rheumatoid arthritis (RA). METHODS: Study subjects were 156 patients with early RA (< 2 yrs). Disease activity, therapeutic response, and radiographic progression were compared in smokers and nonsmokers at 24 months. RESULTS: At baseline, ever-smokers had earlier disease onset and a closer association with the shared epitope (SE), but not more seropositive disease. No significant differences were observed in disease activity and European League Against Rheumatism therapeutic responses between smokers and nonsmokers. Multivariate analysis showed that baseline Larsen score, the HLA-DRB*04 genotype, being female, and current smoking were associated with radiographic progression. CONCLUSION: In patients with early RA, smoking was associated with earlier disease onset and the SE. Smoking was an independent factor of radiographic progression. PMID- 22045839 TI - Ethnic influence in clinical and functional measures of Brazilian patients with spondyloarthritis. AB - OBJECTIVE: Spondyloarthritides (SpA) can present different disease spectra according to ethnic background. The Brazilian Registry of Spondyloarthritis (RBE) is a nationwide registry that comprises a large databank on clinical, functional, and treatment data on Brazilian patients with SpA. The aim of our study was to analyze the influence of ethnic background in SpA disease patterns in a large series of Brazilian patients. METHODS: A common protocol of investigation was prospectively applied to 1318 SpA patients in 29 centers distributed through the main geographical regions in Brazil. The group comprised whites (65%), African Brazilians (31.3%), and people of mixed origins (3.7%). Clinical and demographic variables and various disease index scores were compiled. Ankylosing spondylitis (AS) was the most frequent disease in the group (65.1%); others were psoriatic arthritis (18.3%), undifferentiated SpA (6.8%), enteropathic arthritis (3.7%), and reactive arthritis (3.4%). RESULTS: White patients were significantly associated with psoriasis (p = 0.002), positive HLA-B27 (p = 0.014), and use of corticosteroids (p < 0.0001). Hip involvement (p = 0.02), axial inflammatory pain (p = 0.04), and radiographic sacroiliitis (p = 0.025) were associated with African Brazilian descent. Sex distribution, family history, and presence of peripheral arthritis, uveitis, dactylitis, urethritis, and inflammatory bowel disease were similar in the 3 groups, as well as age at disease onset, time from first symptom until diagnosis, and use of anti-tumor necrosis factor-alpha agents (p > 0.05). Schober test and thoracic expansion were similar in the 3 groups, whereas African Brazilians had higher Maastricht Ankylosing Spondylitis Enthesitis Scores (p = 0.005) and decreased lateral lumbar flexion (p = 0.003), while whites had a higher occiput-to-wall distance (p = 0.02). African Brazilians reported a worse patient global assessment of disease (p = 0.011). Other index scores and prevalence of work incapacity were similar in the 3 groups, although African Brazilians had worse performance in the Ankylosing Spondylitis Quality of Life questionnaire (p < 0.001). CONCLUSION: Ethnic background is associated with distinct clinical aspects of SpA in Brazilian patients. African Brazilian patients with SpA have a poorer quality of life and report worse disease compared to whites. PMID- 22045840 TI - Biological drug treatment of rheumatoid arthritis and spondyloarthritis: effects on QT interval and QT dispersion. AB - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) antagonists bring about significant improvement in chronic inflammatory diseases such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). There is some evidence that they can also have negative myocardial effects, but to date this issue has not been clarified. We evaluated changes in electrocardiographic measures [QT interval, corrected, dispersion, and dispersion corrected (QT, QTc, QTd, QTdc, respectively)] in patients with RA or SpA treated with anti-TNF agents (infliximab and etanercept), those treated with other biological agents (rituximab), and with methotrexate. METHODS: We studied 38 consecutive patients with RA (21 patients) or SpA (19 patients) being treated with TNF-alpha antagonists, 8 patients with RA being treated with rituximab, and 13 patients (8 with RA and 5 with SpA) taking methotrexate. Electrocardiographs (ECG) were performed on all participants at baseline and 12 months after initiation of treatment, and the QT, QTc, and QTd were calculated with standard procedures. RESULTS: After 12 months of treatment, significant increases over baseline values were observed in the mean QT (p < 0.009), QTd (p < 0.0001), and QTdc (p < 0.0001) of the anti-TNF group, but no significant changes were observed in those taking rituximab. QT changes in the anti-TNF group were unrelated to the disease (RA vs SpA) or drug (infliximab vs etanercept), and none were associated with clinical manifestations of cardiac disease. CONCLUSION: In patients with RA and SpA, TNF alpha antagonists seem to increase the QT and QTd measures. Although these changes were completely asymptomatic, ECG may be indicated in patients being considered for anti-TNF therapy to identify those at risk for cardiac complications. PMID- 22045841 TI - Association between Thr21Met and Ser89Asn polymorphisms of the urotensin II gene and systemic sclerosis. AB - OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune chronic fibrotic disorder. Urotensin II (U-II) is predominantly a vasoactive peptide with fibrotic and prothrombotic features. Like endothelin-1 (ET-1), U-II could play an important role in SSc pathogenesis. We evaluated the possible role of the U-II gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to SSc in a Turkish population. METHODS: A total of 189 patients with SSc and 205 healthy controls were enrolled in our study. We analyzed the genotype and allele frequencies of the U-II (UTS2) gene polymorphisms Thr21Met and Ser89Asn in patients with SSc and in controls. RESULTS: We found that the Thr21Met polymorphism of the UTS2 gene was markedly associated with the risk of developing SSc (p < 0.0001), but there was no relationship between the Ser89Asn polymorphism and SSc (p > 0.05). Two haplotypes (MS and TS) were markedly associated with SSc (p < 0.05). There were significant associations between the genotype and allele frequencies of UTS2 gene Thr21Met polymorphism and cases with diffuse or limited SSc, systemic or lung involvement, finger flexion deformity, pitting scars at the fingertips, positive anticentromere, or positive antitopoisomerase 1 antibody groups. CONCLUSION: Our study shows the association between Thr21Met, but not Ser89Asn, in the UTS2 gene and SSc. The results strongly suggest that this single nucleotide polymorphism may be an important risk factor in the development of SSc, and a powerful indicator of severe skin and lung involvement in patients with SSc. PMID- 22045842 TI - Association of IL-12B genetic polymorphism with the susceptibility and disease severity of ankylosing spondylitis. AB - OBJECTIVE: Interleukin 23 (IL-23) stimulates the differentiation of T helper 17 (Th17) cells, which are involved in the pathogenesis of ankylosing spondylitis (AS). Binding of IL-23 to the IL-23 receptor complex activates Janus kinases 2 and tyrosine kinase 2, which phosphorylate IL-23R and subsequently promote the transcription of the IL-17 gene. IL-12B encodes a p40 subunit common to IL-12 and IL-23. We evaluated the effects of IL-12B and IL-23R genotype on the occurrence and clinical features of AS. METHODS: A total of 362 patients with AS and 362 healthy controls were enrolled in the study. Genotypes of IL-12B A1188C (rs3212227) and IL-23R C2370A (rs10889677) were identified by polymerase chain reaction/restriction fragment-length polymorphism. Disease activity and functional status were assessed by Bath AS indices. RESULTS: Subjects carrying IL 12B CC [matched relative risk (RR(m)) 1.93, 95% CI 1.23-3.03] and IL-12B AC (RR(m) 1.73, 95% CI 1.21-2.46) genotypes had a significantly greater risk of developing AS than subjects with the IL-12B AA genotype. Subjects carrying both IL-12B CC and IL-23R AA genotypes also had a significantly higher risk (RR(m) 2.98, 95% CI 1.51-5.89) of developing AS compared to those with IL-12B AA and IL 23R CC/CA genotypes, and this interaction between IL-12B and IL-23R was significant. Patients with AS who had IL-12B CC and IL-12B AC genotypes had an obviously increased Bath Ankylosing Spondylitis Disease Activity Index score compared to those who carried the IL-12B AA genotype (4.3 vs 3.7). CONCLUSION: The IL-12B A1188C genotype was associated with the development and disease severity of AS. PMID- 22045843 TI - Pathways of microvascular permeability in the synovium of normal and diseased human knees. AB - OBJECTIVE: Our study uses the entire proteomes of serum and synovial fluid (SF) to characterize the avenues of microvascular egress of plasma proteins, and quantifies that traffic in normal and diseased human knees. METHODS: Paired aliquots of serum and SF were collected from 17 knees of 11 subjects who died without evident joint disease and 16 patients with clinical effusions, fractionated by gel filtration chromatography and analyzed as continuous plots of the SF/serum concentration ratio versus molecular radius from 1 to 12 nanometers (nm). Curve-stripping methodology, a 3-pore model, and known protein kinetics were then applied to estimate the dimensions of and the net outflow through fenestral, "small," and "large" apertures in the microvascular endothelium. RESULTS: The 3-pore model correlated highly with the observed data (r = 0.992 in normal and 0.980 in arthritis), yielding the following mean values: for the fenestra, the normal radius (nm) was 1.75 and the effused 3.5, and the normal flow (MUl/min) was 1.74 and the arthritic 22.0; for the small pore, the normal radius was 8.6 and the effused 8.5, and the normal flow was 1.5 and the arthritic flow 9.1; for the large pore, the normal radius was 40 and the effused 36, and the normal flow was 0.24 and the arthritic flow 15.5. CONCLUSION: These findings provide the first functional definition of synovial, endothelial fenestrae; reveal that the "increased vascular permeability" of inflammation is not limited to interendothelial gaps; present evidence suggesting that glycocalyceal damage and aquaporin upregulation may affect permeability in arthritic synovium; and define a straightforward methodology for interpretation of biomarker concentrations in arthritic SF. PMID- 22045844 TI - Patient-reported outcome in psoriatic arthritis: a comparison of Web-based versus paper-completed questionnaires. AB - OBJECTIVE: Patients followed in observational cohorts often complete patient reported outcomes on paper questionnaires. With advances in technology, Web-based (WB) formats have been developed. The aims of our study were to determine whether WB and paper-based questionnaires (PB) completed by patients followed in the psoriatic arthritis (PsA) clinic are comparable; whether there is a patient preference for one method or the other; and whether any preference is related to patient characteristics. METHODS: Consecutive patients followed at the PsA clinic completed the Health Assessment Questionnaire, Medical Outcomes Study Short Form 36, fatigue scale, Dermatology Life Quality Index, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life Instrument, and EQ-5D both on paper (PB) and on computer by Internet (WB). Patients were also asked to complete questionnaires regarding their preference for one method or the other. Descriptive statistics and interclass correlation coefficients (ICC) were calculated. RESULTS: Of 110 patients who agreed to participate, 67 (57.3%) successfully completed both PB and WB questionnaires. These patients did not differ from those who did not complete the questionnaires. WB and PB questionnaires took the same length of time to complete, with 20% of the patients complaining of more pain following completion of the questionnaires, more so with the PB. There was excellent agreement between the PB and WB (ICC 0.89-0.97) for all questionnaires. CONCLUSION: The PB and WB versions of 10 standardized self-administered questionnaires in patients with PsA were comparable. The WB format was well accepted by PsA outpatients. Patients may thus be offered a choice of format as well as the choice to complete the questionnaires either in the clinic or remotely by Internet. PMID- 22045846 TI - The importance of CD4 count, viral load and highly active antiretroviral therapy in HIV-associated thrombotic thrombocytopenic purpura (TTP). AB - A case is reported of HIV-associated thrombotic thrombocytopenic purpura with normal CD4 count but high HIV viral load, developing neurological and cardiac complications up to 36 days after initiation of plasma exchange, but remitting within 18 days of the start of highly active antiretroviral therapy and steroids. In addition to plasma exchange, prompt initiation of highly active antiretroviral therapy in patients with HIV-associated thrombotic thrombocytopenic purpura may be justified despite a normal CD4 count. PMID- 22045845 TI - The autoimmune disease risk allele of UBE2L3 in African American patients with systemic lupus erythematosus: a recessive effect upon subphenotypes. AB - OBJECTIVE: UBE2L3 is associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis in European ancestry populations, and this locus has not been investigated fully in non-European populations. We studied the UBE2L3 risk allele for association with SLE, interferon-alpha (IFN alpha), and autoantibodies in a predominantly African American SLE cohort. METHODS: We studied 395 patients with SLE and 344 controls. The UBE2L3 rs5754217 polymorphism was genotyped using Taqman primer-probe sets, and IFN-alpha was measured using a reporter cell assay. RESULTS: The UBE2L3 rs5754217 T allele was strongly enriched in African American patients with anti-La antibodies as compared to controls, and a recessive model was the best fit for this association (OR 2.55, p = 0.0061). Serum IFN-alpha also demonstrated a recessive association with the rs5754217 genotype in African American patients, and the TT/anti-La positive patients formed a significantly high IFN-alpha subgroup (p = 0.0040). Similar nonstatistically significant patterns of association were observed in the European American patients with SLE. Case-control analysis did not show large allele frequency differences, supporting the idea that this allele is most strongly associated with anti-La-positive patients. CONCLUSION: This pattern of recessive influence within a subgroup of patients may explain why this allele does not produce a strong signal in standard case-control studies, and subphenotypes should be included in future studies of UBE2L3. The interaction we observed between UBE2L3 genotype and autoantibodies upon serum IFN-alpha suggests a biological role for this locus in patients with SLE in vivo. PMID- 22045847 TI - STI clinic demonstrates potential as a location to provide education to parents. PMID- 22045848 TI - Assessing where vulnerable groups fare worst: a global multilevel analysis on the impact of welfare regimes on disability across different socioeconomic groups. AB - BACKGROUND: Investigations on health differences within welfare states between low- and high-socioeconomic groups are mainly conducted in Europe. With the aim of gaining global insight on the extent welfare regimes influence personal disability for the most vulnerable, we explore how these health differences vary between low- and high-socioeconomic groups. METHODS: The World Health Survey data were analysed on 199595 adults from 46 countries using the welfare regime classification developed by Wood and Gough. Multilevel logistic regression was used to estimate welfare regime differences in self-reported disability according to individual educational attainment and employment status. RESULTS: As compared with the low educated in the European-conservative regime, the odds of having a higher prevalence of disability was found among low-educated people residing in the informal-security regime of South Asia, with OR being 3.16 (95% CI 2.23 to 4.47). While state-organised regimes seemed to offer more protection against disability to the low educated, the productivist regime of East Asia trailed closely behind, with OR being 1.10 (95% CI 0.76 to 1.60) for the low educated. Similar findings were also observed in the unemployed. CONCLUSIONS: State organised regimes of Europe and the productivist regime of East Asia seem to contain protecting features against disability for all citizens and especially for the most vulnerable. Apart from the productivist regime of East Asia, the low educated and the unemployed seem to carry the greatest health burden within more insecure regimes, highlighting a deficiency in social provisions within these regimes aimed at protecting the most vulnerable. PMID- 22045849 TI - Epigenetics and environmental exposures. AB - It is becoming increasingly apparent that genetic factors are inadequate to fully explain many processes that shape development and disease. For example, monozygotic twin pairs, despite sharing identical DNA sequences, are often discordant for many traits and diseases, indicating that the same genotype can give rise to distinct phenotypes. This points towards the involvement of additional factors that cannot be explained solely by the sequence of the genome. Epigenetic modifications, defined as heritable changes that do not alter the nucleotide sequence, emerge as key factors that regulate chromatin structure and gene expression and, together with genetic factors, provide the mechanistic basis to understand the biological effects of various classes of environmental exposures. Epigenetic mechanisms explain the ability of certain chemical compounds to initiate biological perturbations that can lead to malignancy, despite being weak mutagens or lacking mutagenic activity altogether-a view that challenges old beliefs and opens new avenues in public health. The field of epigenetics also explains the causal link between certain infectious diseases and cancer, a relationship that was first observed over a century ago and was initially discounted, then fell into oblivion and more recently re-emerged as an important concept in biology. A key feature that distinguishes epigenetic modifications from genetic changes is their reversible nature. This provides exciting prophylactic and therapeutic perspectives, some of which already materialised with the approval of the first drugs that modulate the epigenetic machinery, reinforcing the idea that our genes are not our destiny. PMID- 22045850 TI - Mortality in parents following the death of a child: a nationwide follow-up study from Sweden. AB - BACKGROUND: The death of a young child is so devastating that it can increase the risk of mortality in the grieving parent. Little is known about the impact of an adult child's death on the health of parents. METHODS: The authors conducted a follow-up study between 1980 and 2002 based on a linked-registers database that contains the total Swedish population. The authors examined mortality from all causes, natural causes and unnatural causes among parents following the death of children aged 10-49 years. RESULTS: An increased mortality risk (RR 1.31, 95% CI 1.02 to 1.68) in mothers following the death of a minor child (10-17 years) was found and especially following unnatural deaths (primarily accidents and suicides). Mothers also experienced elevated mortality following the death of an adult child aged 18-25 years (RR 1.15, 95% CI 1.03 to 1.29). Bereavement effects among fathers were more attenuated and chiefly found after >8 years of follow-up. From a short-term perspective (1-3 years), the death of an adult child (>25 years) was somewhat protective for parents. However, over longer follow-up periods, it approached (4-8 years) and exceeded (>8 years) the death risk of the general population. CONCLUSIONS: These findings corroborate and extend earlier findings suggesting elevated mortality risks also following the death of an adult child. PMID- 22045852 TI - A CC' loop decoy peptide blocks the interaction between Act1 and IL-17RA to attenuate IL-17- and IL-25-induced inflammation. AB - Interleukin-17 (IL-17) and IL-25 signaling induce the expression of genes encoding inflammatory factors and are implicated in the pathology of various inflammatory diseases. Nuclear factor kappaB (NF-kappaB) activator 1 (Act1) is an adaptor protein and E3 ubiquitin ligase that is critical for signaling by either IL-17 or IL-25, and it is recruited to their receptors (IL-17R and IL-25R) through heterotypic interactions between the SEFIR [SEF (similar expression to fibroblast growth factor genes) and IL-17R] domain of Act1 and that of the receptor. SEFIR domains have structural similarity with the Toll-IL-1 receptor (TIR) domains of Toll-like receptors and IL-1R. Whereas the BB' loop of TIR is required for TIR-TIR interactions, we found that deletion of the BB' loop from Act1 or IL-17RA (a common subunit of both IL-17R and IL-25R) did not affect Act1 IL-17RA interactions; rather, deletion of the CC' loop from Act1 or IL-17RA abolished the interaction between both proteins. Surface plasmon resonance measurements showed that a peptide corresponding to the CC' loop of Act1 bound directly to IL-17RA. A cell-permeable decoy peptide based on the CC' loop sequence inhibited IL-17- or IL-25-mediated signaling in vitro, as well as IL-17- and IL-25-induced pulmonary inflammation in mice. Together, these findings provide the molecular basis for the specificity of SEFIR-SEFIR versus TIR-TIR domain interactions and consequent signaling. Moreover, we suggest that the CC' loop motif of SEFIR domains is a promising target for therapeutic strategies against inflammatory diseases associated with IL-17 or IL-25 signaling. PMID- 22045851 TI - p53 and microRNA-34 are suppressors of canonical Wnt signaling. AB - Although loss of p53 function and activation of canonical Wnt signaling cascades are frequently coupled in cancer, the links between these two pathways remain unclear. We report that p53 transactivated microRNA-34 (miR-34), which consequently suppressed the transcriptional activity of beta-catenin-T cell factor and lymphoid enhancer factor (TCF/LEF) complexes by targeting the untranslated regions (UTRs) of a set of conserved targets in a network of genes encoding elements of the Wnt pathway. Loss of p53 function increased canonical Wnt signaling by alleviating miR-34-specific interactions with target UTRs, and miR-34 depletion relieved p53-mediated Wnt repression. Gene expression signatures reflecting the status of beta-catenin-TCF/LEF transcriptional activity in breast cancer and pediatric neuroblastoma patients were correlated with p53 and miR-34 functional status. Loss of p53 or miR-34 contributed to neoplastic progression by triggering the Wnt-dependent, tissue-invasive activity of colorectal cancer cells. Further, during development, miR-34 interactions with the beta-catenin UTR affected Xenopus body axis polarity and the expression of Wnt-dependent patterning genes. These data provide insight into the mechanisms by which a p53 miR-34 network restrains canonical Wnt signaling cascades in developing organisms and human cancer. PMID- 22045853 TI - Persistent stimulation with interleukin-17 desensitizes cells through SCFbeta TrCP-mediated degradation of Act1. AB - The proinflammatory cytokine interleukin-17 (IL-17) is important for the immune response to pathogens and also contributes to the pathogenesis of various inflammatory diseases. To avoid persistent inflammation, signaling by the IL-17 receptor (IL-17R), which involves the adaptor protein Act1, must be tightly controlled. Here, we report that persistent stimulation of HeLa cells with IL-17 resulted in degradation of Act1 and desensitization of IL-17R signaling. IL-17 stimulated the Lys48-linked polyubiquitination and degradation of Act1, which was phosphorylation-dependent, similar to the IL-17-dependent degradation of inhibitor of nuclear factor kappaB alpha. Act1 was recruited to SCF (Skp1-cullin 1-F-box)-type E3 ubiquitin ligase complexes containing beta-transducin repeat containing protein 1 (beta-TrCP1) or beta-TrCP2 in a phosphorylation-dependent manner upon stimulation of cells with IL-17. Dominant-negative beta-TrCP or knockdown of beta-TrCP1 and beta-TrCP2 markedly reduced IL-17-induced, phosphorylation-dependent ubiquitination and degradation of Act1. Thus, our studies identify a previously uncharacterized desensitization mechanism, involving the SCFbeta-TrCP-mediated degradation of Act1, that occurs during persistent stimulation with IL-17. PMID- 22045856 TI - Pediatric use of complementary and alternative medicine: legal, ethical, and clinical issues in decision-making. AB - In this article we introduce a series of 8 case scenarios and commentaries and explore the complex legal, ethical, and clinical concerns that arise when pediatric patients and their parents or health care providers use or are interested in using complementary and alternative medicine (CAM). People around the world rely on CAM, so similar issues face clinicians in many countries. In law, few cases have dealt with CAM use. The few that have apply the same general legal principles used in cases that involved conventional care while taking into account considerations unique to CAM. In ethics, as with conventional care, the issues surrounding pediatric CAM use usually involve questions about who the appropriate decision-makers are, on what ethical principles should clinical decision-making rely, and what obligations arise on the part of physicians and other health care providers. Clinical decision-making is made more complex by the relatively limited research on the efficacy and safety of CAM compared with conventional medicine, especially in children, which requires clinicians to make decisions under conditions of uncertainty. The clinical scenarios presented focus on patients who represent a range of ages, clinical conditions, and settings. They act as anchors to explore particular CAM policy issues and illustrate the application of and shortcomings in existing guidance and intervention principles. Although the focus on a pediatric population adds another layer of complexity to the analysis, many of the concepts, issues, principles, and recommendations also apply to adults. PMID- 22045857 TI - Natural health product-drug interactions: evolving responsibilities to take complementary and alternative medicine into account. AB - Natural health products (NHPs) (known as dietary supplements in the United States) are a popular form of self-care, yet many patients do not disclose their use to clinicians. NHP-drug interactions are known to occur and can harm patients and affect the efficacy of conventional treatment. Using the example of an HIV positive adolescent who had been responding well to antiretroviral therapy but then experienced a sudden unexplained deterioration in her condition, we review (1) clinicians' obligation to inquire about complementary and alternative medicine (CAM) use when assessing, treating, and monitoring patients, (2) how clinicians' duty to warn about risks associated with treatment has evolved and expanded, and (3) patients' and parents' responsibility to disclose CAM use. It also addresses the responsibility of hospitals and health facilities to ensure that the reality of widespread CAM/NHP use is taken into account in patient care to effectively protect patients from harm. PMID- 22045858 TI - Treating teens: considerations when adolescents want to use complementary and alternative medicine. AB - In this article we examine decision-making about complementary and alternative medicine use when the patient is an adolescent. A case scenario describes patient parent conflict when a 14-year-old boy who was diagnosed with ulcerative colitis that has continued to progress even with medication refuses recommended surgery despite his physician's and parents' support for that option; he prefers homeopathy instead. We address (1) who has decision-making authority about treatment for young people, (2) how to determine if a young person can consent to or refuse treatment, (3) special considerations when counseling and treating adolescents (whether they can decide about treatment for themselves), and (4) parent-child conflicts about treatment. In addition, we suggest ways that health care providers can foster a trusting relationship with patients and parents. PMID- 22045859 TI - Childhood immunization: when physicians and parents disagree. AB - Persistent fears about the safety and efficacy of vaccines, and whether immunization programs are still needed, have led a significant minority of parents to refuse vaccination. Are parents within their rights when refusing to consent to vaccination? How ought physicians respond? Focusing on routine childhood immunization, we consider the ethical, legal, and clinical issues raised by 3 aspects of parental vaccine refusal: (1) physician counseling; (2) parental decision-making; and (3) continuing the physician-patient relationship despite disagreement. We also suggest initiatives that could increase confidence in immunization programs. PMID- 22045860 TI - Considering complementary and alternative medicine alternatives in cases of life threatening illness: applying the best-interests test. AB - In this article we explore decision-making about treatment when a child faces a life-threatening illness but conventional treatment presents substantial risk and uncertain benefit. When is it acceptable for parents to decide to use complementary and alternative medicine as an alternative, rather than a complement, to conventional care? We use the example of a young child suffering from progressive glycogen storage disease, for whom liver transplant offers the only prospect of a cure. Without a liver transplant, the disease usually results in death within a few years. However, experience using transplant to treat this illness has been limited, success is far from ensured, and the risks (including death and continued progression of the disease) are substantial. The child's parents, who are first-generation immigrants, consider the risks of the transplant unjustified because it still does not offer good prospects for a healthy future. They believe that traditional Chinese medicine could help remediate their daughter's disease. In the article we (1) review parents' obligation to make treatment decisions in the best interests of their child, (2) explain limits on parents' decision-making authority, (3) explore how "best interests" are determined, focusing on cases of serious illness for which conventional treatment is risky and benefit is possible but uncertain, (4) explain the standard of care that physicians must meet in advising about treatment, and (5) outline factors that clinicians and parents should take into account when making decisions. PMID- 22045861 TI - Referrals and shared or collaborative care: managing relationships with complementary and alternative medicine practitioners. AB - In this article we discuss steps that clinicians should take after deciding to include a complementary and alternative medicine (CAM) treatment that is beyond the clinician's expertise in a patient's treatment plan. We use the example of an adolescent patient with chronic recurrent headaches that have not been relieved by medication or other therapies and whose physician refers her to an acupuncturist for treatment. We focus on (1) circumstances under which referral is appropriate, (2) the nature of the relationship between the referring clinician and the practitioner to whom the referral is made (considering conventional health care and CAM, regulated and unregulated practitioners), and (3) considerations when undertaking shared or collaborative care with other health care practitioners (conventional health care or CAM). We also suggest best practices in managing such relationships. PMID- 22045862 TI - Informed consent: advising patients and parents about complementary and alternative medicine therapies. AB - Although research on complementary and alternative medicine (CAM) therapies is still limited, systematic reviews have revealed sufficient evidence to conclude that CAM can be effective for certain conditions. In this article we discuss clinicians' responsibilities to inform parents/patients about CAM alternatives and use the example of acupuncture for chemotherapy-induced nausea and vomiting. Chemotherapy-induced nausea and vomiting remain significant adverse effects of cancer therapy, and some patients cannot find relief with standard therapies. When making decisions for a child with a life-threatening illness, parents must consider all reasonable options and decide what is in the child's best interests. A physician's failure to provide parents with relevant information regarding therapies with the prospect of therapeutic benefit impedes their ability to make an informed decision. Physicians have the ethical duty of beneficence; they must be aware of current research in pain and symptom management and other aspects of care. A physician's duty of care does not necessarily include the obligation to provide information about therapies outside the range of conventional treatment or those not yet supported in the medical literature. However, as CAM therapies such as acupuncture become better studied and their safety and efficacy are established, the scope of disclosure required may expand to include them. The legal and ethical obligation to obtain informed consent to treatment requires disclosure and discussion of therapies when there is reliable evidence of potential therapeutic benefit. At the same time, the more limited state of knowledge regarding effects of a particular therapy in the pediatric population must be factored into decision-making when treating a child. PMID- 22045863 TI - Hospitals and complementary and alternative medicine: managing responsibilities, risk, and potential liability. AB - Patients and families increasingly press hospitals to facilitate provision of complementary and alternative medicine (CAM) therapies and products. At the same time, a growing number of hospitals and health care facilities have taken steps to integrate CAM and conventional care. In this article we consider institutional responsibilities when patients/parents use or are considering CAM. We (1) review hospitals' responsibilities to patients and parents, (2) explain how these principles apply in the case of CAM practitioners and products, (3) address institutional responsibilities for different models of service delivery, and (4) highlight issues that should be addressed when developing institutional policies to govern CAM use and propose ways to do so. PMID- 22045864 TI - Complementary and alternative medicine practitioners' standard of care: responsibilities to patients and parents. AB - In this article we explain (1) the standard of care that health care providers must meet and (2) how these principles apply to complementary and alternative medicine practitioners. The scenario describes a 14-year-old boy who is experiencing back pain and whose chiropractor performed spinal manipulation but did not recognize or take steps to rule out serious underlying disease-in this case, testicular cancer--either initially or when the patient's condition continued to deteriorate despite treatment. We use chiropractic care for a patient with a sore back as an example, because back pain is such a common problem and chiropracty is a common treatment chosen by both adult and pediatric patients. The scenario illustrates the responsibilities that complementary and alternative medicine practitioners owe patients/parents, the potential for liability when deficient care harms patients, and the importance of ample formal pediatric training for practitioners who treat pediatric patients. PMID- 22045865 TI - Concluding comments: maximizing good patient care and minimizing potential liability when considering complementary and alternative medicine. AB - Our goal for this supplemental issue of Pediatrics was to consider what practitioners, parents, patients, institutions, and policy-makers need to take into account to make good decisions about using complementary and alternative medicine (CAM) to treat children and to develop guidelines for appropriate use. We began by explaining underlying concepts and principles in ethical, legal, and clinical reasoning and then used case scenarios to explore how they apply and identify gaps that remain in practice and policy. In this concluding article, we review our major findings, summarize our recommendations, and suggest further research. We focus on several key areas: practitioner and patient/parent relationships; decision-making; dispute resolution; standards of practice; hospital/health facility policies; patient safety; education; and research. Ethical principles, standards, and rules applicable when making decisions about conventional care for children apply to decision-making about CAM as well. The same is true of legal reasoning. Although CAM use has seldom led to litigation, general legal principles relied on in cases involving conventional medical care provide the starting point for analysis. Similarly, with respect to clinical decision-making, clinicians are guided by clinical judgment and the best interests of their patient. Whether a therapy is CAM or conventional, clinicians must weigh the relative risks and benefits of therapeutic options and take into account their patient's values, beliefs, and preferences. Consequently, many of our observations apply to conventional and CAM care and to both adult and pediatric patients. PMID- 22045866 TI - Citrate treatment reduces endothelial death and inflammation under hyperglycaemic conditions. AB - Hyperglycaemia and glucose degradation products (GDPs) are closely associated with oxidative stress and inflammation in diabetic patients, a condition that leads to endothelial dysfunction and cardiovascular problems. We evaluated the effect of citrate and gluconate on glucose- and GDP-induced endothelial inflammation by measuring changes in viability, inflammation and function in primary human umbilical vein endothelial cells (HUVECs). The extent of apoptosis/necrosis was measured by flow cytometry and visualised with confocal microscopy by staining with annexin V or propidium iodide, respectively. Protein kinase C-betaII (PKC-betaII) activation was evaluated with Western blotting. Incubation with glucose (30 mM) and GDP (50 uM) significantly increased PKC betaII expression, endothelial cell death and inflammation. The addition of citrate decreased hyperglycaemia-induced apoptosis (p = 0.021), necrosis (p = 0.04) and reduced PKC-betaII expression (p = 0.021) down to background levels. Citrate improved endothelial function by reducing the inflammatory markers (p = 0.01) and by decreasing neutrophil diapedesis (p = 0.012). These results suggest that citrate may have therapeutic potential by reducing hyperglycaemia-induced endothelial inflammation and abolishing endothelial dysfunction. PMID- 22045867 TI - Potentiation of aspirin-induced cerebroprotection by minocycline: a therapeutic approach to attenuate exacerbation of transient focal cerebral ischaemia. AB - Cerebrovascular disease is a major cause of mortality and disability in adults. Diabetes mellitus increases the risk of cerebral ischaemia and is associated with worse clinical outcome following an event. Upregulation of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in diabetes appears to play a role in vascular complications of diabetes. We hypothesised that inhibition of MMP-2 and MMP-9 by minocycline can be potentiated by aspirin through inhibition of cyclooxygenase-2 and tissue plasminogen activator, resulting in amelioration of clinical cerebral ischaemia in diabetes. In the present study, cerebral ischaemia/reperfusion injury was induced in streptozotocin diabetic rats by 1 h middle cerebral artery occlusion and 24 h reperfusion. Infarct volume, cerebral oedema, neurological severity score and blood-brain barrier disruption were significantly increased in diabetic animals compared with the normoglycemic control group. The combination of aspirin and minocycline treatment significantly improved these parameters in diabetic animals. Moreover, this therapy was associated with significantly lower mortality and reduction in MMP-2 and MMP-9 levels. Our data indicate that combination of aspirin and minocycline therapy protects from the consequences of cerebral ischaemia in animal models of diabetes and is associated with inhibition of MMP-2 and MMP-9. Therefore, this combination therapy may represent a novel strategy to reduce the neurological complications of cerebral ischaemia in diabetes. PMID- 22045868 TI - Natural killer cell-produced IFN-gamma and TNF-alpha induce target cell cytolysis through up-regulation of ICAM-1. AB - NK cells control tumor and virus-infected cells through releasing cytotoxic granules and proinflammatory cytokines. IFN-gamma and TNF-alpha secretions and cytotoxicity are regarded as two distinct functions of NK cells with little synergy in between as results of early association of the two functions with distinct subsets of NK populations and of the studies showing target cells developing NK resistance upon IFN-gamma treatment. Here, we show that IFN-gamma and TNF-alpha synergistically enhance NK cell cytotoxicity through NF-kappaB dependent up-regulation of ICAM-1 expression in target cells, thereby promoting their conjugate formation with NK cells. Neutralizing IFN-gamma and TNF-alpha during cytolysis significantly impaired NK cell lysis of the target cells. Further, tumor cells exhibiting IFN-gamma-inducible lysis are generally less sensitive NK target cells but express inducible levels of ICAM-1. In contrast, sensitive NK targets tend to express higher but less-inducible ICAM-1. Their preferential induction in the lysis of insensitive NK target cells suggests that IFN-gamma and TNF-alpha are functionally linked to and should be regarded as an integral part of NK cytolytic function. PMID- 22045869 TI - IL-27 inhibits pathophysiological intraocular neovascularization due to laser burn. AB - AMD is the most common disease leading to acquired blindness in developed countries. CNV is the foremost cause of AMD and is thought to be induced by regional inflammation as a result of age-related conformational changes of the chorioretinal interface. Here, we show that IL-27, a member of the IL-6/IL-12 cytokine family, has an angiostatic effect and regulates the development of laser induced experimental CNV in mice. In this model, IL-27 expression increased in the damaged choroid and peaked at the 24 h-time-point. IL-27 neutralization, induced by inoculating an antagonistic antibody into the vitreous cavity, enhanced VEGF production and the extent of CNV. By contrast, the administration of rIL-27 reduced VEGF production and the extent of CNV. Mice deficient in the EBI3, which lack IL-27, also showed more CNV than C57BL/6 mice, and this was reduced by IL-27 supplementation. We additionally investigated the effect of IL 27 on the function of macrophages, which play a critical role in CNV. IL-27 did not affect macrophage migration but inhibited its VEGF production. IL-27 therefore appears to regulate CNV and is a promising candidate target for treating sight-threatening diseases caused by ocular neovascularization. PMID- 22045870 TI - Transcriptional activation of the IL31 gene by NFAT and STAT6. AB - IL-31, a newly identified member of the IL-6 cytokine family, is involved in many pathological conditions, including atopic dermatitis and pruritis. In this study, we investigated how expression of IL-31 is regulated in T cells and mast cells. We observed that expression of IL-31 required a calcium signal and was dependent on the calcineurin-NFAT signaling pathway. Moreover, we found that IL-31 promoter contains a positive regulatory region that mediates calcium- and IL-4-dependent induction of the IL-31 gene and demonstrated that a change into an open chromatin conformation occurs in this region after stimulation with calcium and IL-4. Whereas IL-4 responsiveness required STAT6 binding sites, calcium responsiveness of IL-31 promoter required NFAT binding sites that bind NFATc1 and NFATc2 in vitro and in vivo. The induction of IL-31 promoter activity was impaired when these sites were mutated but was enhanced by CA-NFATc1 or STAT6 proteins and further increased synergistically by combinations of both proteins. Furthermore, the importance of STAT6 proteins was indicated by impaired, IL-4-mediated induction of IL-31 in STAT6-diminished Jurkat cells. Thus, our data demonstrate that calcium and IL-4 signals are required to mediate induction of IL-31 in Th2 cells and mast cells and that this induction appears to result from specific binding of NFAT and STAT6 proteins. PMID- 22045871 TI - Bronchiectasis in patients with COPD: a distinct COPD phenotype? PMID- 22045872 TI - Childhood asthma: the need for a personalized "whole child" approach. PMID- 22045873 TI - Oral appliances and sleep-disordered breathing. PMID- 22045874 TI - From telemedicine to a critical care database: a new resource for national benchmarking. PMID- 22045875 TI - Point: will public reporting of health-care quality measures inform and educate patients? Yes. PMID- 22045876 TI - Counterpoint: will public reporting of health-care quality measures inform and educate patients? No. PMID- 22045877 TI - Rare lung disease research: strategies for improving identification and recruitment of research participants. AB - Research in rare lung diseases faces methodologic limitations by virtue of the small number of participants available to be studied. We explored several strategies that may improve researchers' ability to identify and recruit research participants with rare lung diseases. We provide an overview of strategies based on available evidence, previously used approaches, and reasoning. First, disease detection is generally poor and may be improved through strategies targeted at primary care practitioners or directly at patients, thus increasing the pool of patients available for research studies. Next, standardization of case definitions in rare lung diseases is often lacking, hindering research recruitment efforts because of confusion over appropriate recruitment criteria. Expert consensus statements can enhance both clinical care and research recruitment by standardizing definitions. Finally, recruitment strategies using rare lung disease registries, clinical research networks, novel Internet-based direct patient recruitment approaches, and patient organizations may facilitate recruitment of patients with rare lung diseases. In summary, although several strategies for improving the identification and recruitment of research participants with rare lung diseases have been proposed, published examples are few. Objective measurement and reporting of novel recruitment methods and collaboration among researchers facing the same limitations across various rare lung diseases are required. Advancements in this area are vital to the design and performance of much-needed robust clinical studies across the spectrum of rare lung diseases. PMID- 22045878 TI - Thoracic ultrasonography for the pulmonary specialist. AB - Thoracic ultrasonography is a noninvasive and readily available imaging modality that has important applications in pulmonary medicine outside of the ICU. It allows the clinician to diagnose a variety of thoracic disorders at the point of care. Ultrasonography is useful in imaging lung consolidation, pleural-based masses and effusions, pneumothorax, and diaphragmatic dysfunction. It can identify complex or loculated effusions and be useful in planning treatment. Identifying intrathoracic mass lesions can guide sampling by aspiration and biopsy. This article summarizes thoracic ultrasonography applications for the pulmonary specialist, related procedural codes, and reimbursement. The major concepts are illustrated with cases. These case summaries are enhanced with online supplemental videos and chest radiograph, chest CT scan, and ultrasound correlation. PMID- 22045879 TI - American College of Chest Physicians consensus statement on the use of topical anesthesia, analgesia, and sedation during flexible bronchoscopy in adult patients. AB - BACKGROUND: Optimal performance of bronchoscopy requires patient's comfort, physician's ease of execution, and minimal risk. There is currently a wide variation in the use of topical anesthesia, analgesia, and sedation during bronchoscopy. METHODS: A panel of experts was convened by the American College of Chest Physicians Interventional/Chest Diagnostic Network. A literature search was conducted on MEDLINE from 1969 to 2009, and consensus was reached by the panel members after a comprehensive review of the data. Randomized controlled trials and prospective studies were given highest priority in building the consensus. RESULTS: In the absence of contraindications, topical anesthesia, analgesia, and sedation are suggested in all patients undergoing bronchoscopy because of enhanced patient tolerance and satisfaction. Robust data suggest that anticholinergic agents, when administered prebronchoscopy, do not produce a clinically meaningful effect, and their use is discouraged. Lidocaine is the preferred topical anesthetic for bronchoscopy, given its short half life and wide margin of safety. The use of a combination of benzodiazepines and opiates is suggested because of their synergistic effects on patient tolerance during the procedure and the added antitussive properties of opioids. Propofol is an effective agent for sedation in bronchoscopy and can achieve similar sedation, amnesia, and patient tolerance when compared with the combined administration of benzodiazepines and opiates. CONCLUSIONS: We suggest that all physicians performing bronchoscopy consider using topical anesthesia, analgesic and sedative agents, when feasible. The existing body of literature supports the safety and effectiveness of this approach when the proper agents are used in an appropriately selected patient population. PMID- 22045880 TI - Negative pressure pulmonary edema following bronchospasm. AB - Negative pressure pulmonary edema (NPPE) is an important cause of noncardiogenic pulmonary edema but is rarely reported in the setting of bronchospasm. A 43-year old woman with severe reactive airway disease suffered an episode of severe bronchospasm after endotracheal extubation following an otherwise uneventful general anesthetic. Subsequently, she developed clinical and radiographic signs of pulmonary edema in the absence of other symptoms of acute left-sided heart failure, leading to the diagnosis of noncardiogenic pulmonary edema. She received noninvasive positive pressure ventilation for a few hours, after which her clinical and radiologic signs and symptoms of pulmonary edema were greatly improved. This clinical scenario strongly suggests NPPE. We submit that it is possible to create NPPE by generating highly negative intrathoracic pressures in the setting of severe bronchospasm. PMID- 22045881 TI - Long-term disease-free survival of a patient with synchronous bilateral lung adenocarcinoma displaying different EGFR and C-MYC molecular characteristics. AB - The main difficulty with multiple lung tumors is distinguishing synchronous and metachronous lesions from second independent primary tumors, particularly when dealing with the same histologic type. Challenging diagnostic hurdles may explain, at least in part, the extremely variable (0%-79%) 5-year survival rate. We present a case report of a patient with synchronous primary adenocarcinoma treated with surgery that exhibited different EGFR gene status, with an exon 19 mutation in the adenocarcinoma of the left upper lobe that was absent in the right upper lobe. Further, specific EGFR and C-MYC amplification events were associated only with the EGFR-mutated lesion. According to an independent evolution theory, these events were classified as early stage, and the patient is still alive and free of disease 70 months after surgery. Molecular evaluation was an important tool to support the diagnosis of synchronous primary adenocarcinoma, which had not been possible with the application of Martini-Melamed criteria. PMID- 22045882 TI - Toxicology in the ICU: part 3: natural toxins. AB - This is the third article of a three-part series that reviews the care of poisoned patients in the ICU. This article focuses on natural toxins, such as heavy metals and those produced by plants, mushrooms, arthropods, and snakes. The first article discussed the general approach to the patient, including laboratory testing; the second article focused on specific toxic agents, grouped into categories. PMID- 22045883 TI - Anterior mediastinal bone-eroding mass with disseminated lung lesions. PMID- 22045884 TI - A 20-year-old man with fever, chest pain, and lung nodules. PMID- 22045885 TI - Visual vs automated assessment of emphysema. PMID- 22045886 TI - Overlooking cardiovascular risk in patients with COPD. PMID- 22045887 TI - Chest ultrasonography as a replacement for chest radiography in the ED. PMID- 22045888 TI - Lung transplantation in coal workers pneumoconiosis. PMID- 22045889 TI - Serum procalcitonin and infective exacerbations of asthma. PMID- 22045890 TI - MRI in acute pulmonary embolism: a valuable alternative in the assessment of suspected acute pulmonary embolism. PMID- 22045891 TI - Influence of flavonoid extracts from celery on oxidative stress induced by dichlorvos in rats. AB - The present work was to investigate the effects of flavonoid extracts from celery on oxidative stress induced by dichlorvos (DIC) in male Wistar rats maintained on a normal diet. The rats were given DIC through intragastric administration by the dose of 7.2 mg/kg.body weight (bw)/day and additionally added 5% flavonoid extracts to the diet for 4 weeks continuously. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione-S transferase (GST) and the content of malondialdehyde (MDA) in livers of rats were measured at the end of the experiment. Under the influence of DIC, there were significant decrease in the activities of SOD, CAT and GST and significant increase in GPx activity and MDA content. The results also showed that the activities of SOD, GST and CAT in the DIC-treated group declined significantly when compared with the flavonoid extracts group and the DIC + flavonoid extracts group, respectively. With regard to GPx activity and MDA content, significant increase were showed in the DIC-treated group in comparison to those in the flavonoid extracts group and the DIC + flavonoid extracts group, respectively. The observations presented lead us to conclude the harmful effects of DIC during the exposure and the protective role of flavonoids in minimizing these effects. PMID- 22045892 TI - Effects of erdosteine on hemostasis: an experimental study. AB - AIM: In this study, the effects of erdosteine (ED) on the platelet function and coagulation were investigated in adult rats. MATERIALS AND METHOD: Twenty-eight male Wistar albino rats were divided into four groups. The control rats in group I (n = 7) were given only 0.5 cc of normal saline daily through oral gavage. Group II (n = 7) rats were administered 3 mg/kg ED through oral gavage for 3 days; while group III (n = 7) rats were given 10 mg/kg ED through oral gavage for 3 days; and group IV (n = 7) rats were administered 30 mg/kg ED through oral gavage for 3 days. Prothrombin time (PT), activated prothromboplastin time (aPTT), international normalized ratio (INR), coagulation factors and complete blood counts were measured from the blood drawn. RESULTS: There were a lot of differences between ED groups and control group, and among ED groups. The found differences were level of PT, aPTT, INR, coagulation factors, and number of platelets. DISCUSSION: We consider that ED which is used as a mucolytic agent in child clinics may affect hemostasis and coagulation in a dose-dependent manner. ED should be used carefully by the patients with coagulation disorders, since there is no information available in the package insert and literature screening regarding the effect of ED. PMID- 22045893 TI - Successful therapy with hemoperfusion and plasma exchange in acute 1,2,3 trichloropropane poisoning. AB - 1,2,3-trichloropropane (1,2,3-TCP) is commonly used as an intermediate in pesticide and an industrial specialty solvent. Acute 1,2,3-TCP poisoning is rare but a medical emergency. Sporadic cases of toxic hepatic injury from 1,2,3-TCP in humans have been reported. Liver is a target organ for 1,2,3-TCP toxicity, which may ensue in a short period after ingestion. A specific antidote against 1,2,3 TCP is not available. So it is important to distinguish that a patient with 1,2,3 TCP poisoning constitutes a medical emergency. In this case study, the poisoned patient's clinical condition and laboratory values improved gradually after she received hemoperfusion (HP) and plasma exchange, which indicated that the therapy with HP and plasma exchange were helpful in the treatment of 1,2,3-TCP poisoning. PMID- 22045894 TI - Throat infections. PMID- 22045895 TI - Arthritis in children and adolescents. PMID- 22045896 TI - Consultation with the specialist: Asperger syndrome. PMID- 22045897 TI - Ethics for the pediatrician: genetic testing and newborn screening. PMID- 22045898 TI - Index of suspicion: Case 1: Abdominal trauma, pain, and tenderness associated with anemia and hematuria in a 14-year-old boy. Case 2: Ptosis, diplopia, tremors, and mild exophthalmos in a 9-year-old girl. Case 3: Persistent cough, shortness of breath, and localized decreased aeration in an 18-year-old girl. PMID- 22045900 TI - Bipolar disorders. PMID- 22045901 TI - Visual diagnosis: a 10-year-old boy with a persistent rash since birth. PMID- 22045902 TI - The importance of participant demographics. PMID- 22045903 TI - Mentorship for Alcohol Problems (MAP): a peer to peer modular intervention for outpatients. AB - AIMS: This is a Stage I open pilot to develop a new intervention, Mentorship for Alcohol Problems (MAP), for individuals with alcohol-use disorders in community treatment programs. METHODS: Ten mentors participated for 6 months until 30 mentees received MAP for 12 weeks. Behavioral and biological measures were conducted in addition to fidelity measures. Four focus groups were held with participants and clinician feedback surveys were completed. RESULTS: Feasibility and acceptance data in the domains of patient interest, safety and satisfaction were promising. Mentees reduced their alcohol and substance use and the majority of mentors sustained abstinence. Fidelity measures indicated that mentors adhered to the delivery of treatment. CONCLUSION: MAP shows promise to be incorporated into professionally run outpatient alcohol treatment programs to assist in the reduction of alcohol and substance use. PMID- 22045904 TI - Prevnar 13, the new 13-valent pneumococcal conjugate vaccine. AB - OBJECTIVE: To review the immunogenicity, efficacy, and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in pediatric patients. DATA SOURCES: A MEDLINE search (2000-September 2011) was conducted using the key words Streptococcus pneumoniae and pneumococcal conjugate vaccine for clinical trials, limited to studies conducted in humans and published in English. STUDY SELECTION AND DATA EXTRACTION: Randomized, controlled, multicenter trials were reviewed and included to evaluate the safety and efficacy of PCV13. Literature on the epidemiology and pathology of pneumococcal infections and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed. DATA SYNTHESIS: PCV13 is approved for routine vaccination of all infants as a 4-dose series at age 2, 4, 6, and 12-15 months for children who previously received 1 or more doses of the 7-valent pneumococcal conjugate vaccine (PCV7), and for children with underlying medical conditions that increase their risk for pneumococcal disease or its complications. PCV13 has comparable immunogenicity to the serotypes common with PCV7 and also provides protection against 6 additional pneumococcal serotypes. PCV13 has also been shown to have a comparable adverse reaction profile to PCV7. CONCLUSIONS: Based on published immunogenicity and safety data, as well as the recent recommendations by the ACIP for routine use in infants and indications for high-risk pediatric patients, PCV13 is a revised formulation of pneumococcal vaccine that should be included on pharmacy formularies. PMID- 22045905 TI - Ferumoxytol use as an intravenous contrast agent for magnetic resonance angiography. AB - OBJECTIVE: To evaluate the efficacy and safety of ferumoxytol for use in magnetic resonance angiography (MRA) of the vasculature. DATA SOURCES: Literature was accessed through MEDLINE (1946-September 2011) and EMBASE (1947-September 2011) using the terms ferumoxytol, magnetic resonance imaging and angiography, blood pool agent, and superparamagnetic iron oxide. Reference citations from identified publications were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All English-language articles and human studies (N = 9) were identified that evaluated ferumoxytol use in magnetic resonance imaging (MRI). Articles that evaluated the use of the drug in first-pass and equilibrium phase imaging of the vasculature were included (n = 4). DATA SYNTHESIS: Contrast agents for MRI improve disease characterization and diagnosis. Ferumoxytol, a medication approved for treatment of iron deficiency anemia in adults with chronic kidney disease, has superparamagnetic properties. As a blood pool agent, ferumoxytol remains primarily in the intravascular space. Therefore, its use in MRI may increase image sensitivity and specificity and have a decreased adverse effect profile compared to other contrast agents. Specifically, ferumoxytol may be an option for MRA, a specific type of MRI that images blood vessels. In the 4 studies evaluated here, ferumoxytol was administered primarily to healthy adults as an accumulative dose of 4 mg Fe/kg injected at 1 mL/sec. Not all studies reported adverse events and addressed safety monitoring. The evaluated studies are limited by small size, open-label design, and noncomparative methodology. CONCLUSIONS: Data from small pilot studies suggest that ferumoxytol may improve image quality in MRA; however, further investigation is necessary to establish its efficacy and safety. Large randomized, active-comparator trials are needed to establish optimal dosing, imaging procedures, and safety monitoring. PMID- 22045907 TI - Intersection of quality metrics and Medicare policy. AB - The federal government is increasing its push for a high-value health care system by increasing transparency and accountability related to quality. The Medicare program has begun to publicly rate the quality of Medicare plans, including prescription drug plans, and is transforming its payment policies to reward plans that deliver the highest levels of quality. These policies will have a cascade effect on pharmacies and pharmacists as the Medicare plans look for assistance in improving the quality of medication use. This commentary describes the Medicare policies directed toward improvement of quality and their effect on pharmacy payment and opportunities for pharmacists to affirm their role in a high-quality medication use system. PMID- 22045908 TI - Linaclotide: a novel approach to the treatment of irritable bowel syndrome. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of linaclotide for irritable bowel syndrome (IBS). DATA SOURCES: A literature search using PubMed (1966-August 2011) and International Pharmaceutical Abstracts (1970 July 2011) was conducted using the terms linaclotide and MD-1100. Additional publications were identified by reviewing bibliographies. Abstracts were included in the absence of published full studies. Product information was requested from the manufacturer. STUDY SELECTION AND DATA EXTRACTION: The search was limited to English-language publications. All available clinical trials of linaclotide pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of linaclotide as a treatment for IBS were included. Animal studies were included in the absence of data in humans. DATA SYNTHESIS: Linaclotide is a guanylate cyclase C agonist currently being studied in Phase 3 trials for the treatment of IBS with constipation. Controlled clinical trials have found that linaclotide significantly improves the number of complete spontaneous bowel movements per week, in addition to symptoms such as abdominal pain/discomfort, bloating, and straining. The most common adverse event associated with linaclotide is diarrhea. CONCLUSIONS: Linaclotide appears to be a safe and effective treatment for IBS. Additional clinical trials will more fully elucidate the safety profile of linaclotide and better define its place in therapy. PMID- 22045909 TI - Identification of cancer genomic markers via integrative sparse boosting. AB - In high-throughput cancer genomic studies, markers identified from the analysis of single data sets often suffer a lack of reproducibility because of the small sample sizes. An ideal solution is to conduct large-scale prospective studies, which are extremely expensive and time consuming. A cost-effective remedy is to pool data from multiple comparable studies and conduct integrative analysis. Integrative analysis of multiple data sets is challenging because of the high dimensionality of genomic measurements and heterogeneity among studies. In this article, we propose a sparse boosting approach for marker identification in integrative analysis of multiple heterogeneous cancer diagnosis studies with gene expression measurements. The proposed approach can effectively accommodate the heterogeneity among multiple studies and identify markers with consistent effects across studies. Simulation shows that the proposed approach has satisfactory identification results and outperforms alternatives including an intensity approach and meta-analysis. The proposed approach is used to identify markers of pancreatic cancer and liver cancer. PMID- 22045910 TI - Competing risks regression for clustered data. AB - A population average regression model is proposed to assess the marginal effects of covariates on the cumulative incidence function when there is dependence across individuals within a cluster in the competing risks setting. This method extends the Fine-Gray proportional hazards model for the subdistribution to situations, where individuals within a cluster may be correlated due to unobserved shared factors. Estimators of the regression parameters in the marginal model are developed under an independence working assumption where the correlation across individuals within a cluster is completely unspecified. The estimators are consistent and asymptotically normal, and variance estimation may be achieved without specifying the form of the dependence across individuals. A simulation study evidences that the inferential procedures perform well with realistic sample sizes. The practical utility of the methods is illustrated with data from the European Bone Marrow Transplant Registry. PMID- 22045911 TI - Boundary detection in disease mapping studies. AB - In disease mapping, the aim is to estimate the spatial pattern in disease risk over an extended geographical region, so that areas with elevated risks can be identified. A Bayesian hierarchical approach is typically used to produce such maps, which represents the risk surface with a set of random effects that exhibit a single global level of spatial smoothness. However, in complex urban settings, the risk surface is likely to exhibit localized rather than global spatial structure, including areas where the risk varies smoothly over space, as well as boundaries separating populations that are geographically adjacent but have very different risk profiles. Therefore, this paper proposes an approach for capturing localized spatial structure, including the identification of such risk boundaries. The effectiveness of the approach is tested by simulation, before being applied to lung cancer incidence data in Greater Glasgow, UK, between 2001 and 2005. PMID- 22045912 TI - Strain-specific modifier genes of Cecr2-associated exencephaly in mice: genetic analysis and identification of differentially expressed candidate genes. AB - Although neural tube defects (NTDs) are common in humans, little is known about their multifactorial genetic causes. While most mouse models involve NTDs caused by a single mutated gene, we have previously described a multigenic system involving susceptibility to NTDs. In mice with a mutation in Cecr2, the cranial NTD exencephaly shows strain-specific differences in penetrance, with 74% penetrance in BALB/cCrl and 0% penetrance in FVB/N. Whole genome linkage analysis showed that a region of chromosome 19 was partially responsible for this difference in penetrance. We now reveal by genetic analysis of three subinterval congenic lines that the chromosome 19 region contains more than one modifier gene. Analysis of embryos showed that although a Cecr2 mutation causes wider neural tubes in both strains, FVB/N embryos overcome this abnormality and close. A microarray analysis comparing neurulating female embryos from both strains identified differentially expressed genes within the chromosome 19 region, including Arhgap19, which is expressed at a lower level in BALB/cCrl due to a stop codon specific to that substrain. Modifier genes in this region are of particular interest because a large portion of this region is syntenic to human chromosome 10q25, the site of a human susceptibility locus. PMID- 22045913 TI - Gene expression analysis of whole blood, peripheral blood mononuclear cells, and lymphoblastoid cell lines from the Framingham Heart Study. AB - Despite a growing number of reports of gene expression analysis from blood derived RNA sources, there have been few systematic comparisons of various RNA sources in transcriptomic analysis or for biomarker discovery in the context of cardiovascular disease (CVD). As a pilot study of the Systems Approach to Biomarker Research (SABRe) in CVD Initiative, this investigation used Affymetrix Exon arrays to characterize gene expression of three blood-derived RNA sources: lymphoblastoid cell lines (LCL), whole blood using PAXgene tubes (PAX), and peripheral blood mononuclear cells (PBMC). Their performance was compared in relation to identifying transcript associations with sex and CVD risk factors, such as age, high-density lipoprotein, and smoking status, and the differential blood cell count. We also identified a set of exons that vary substantially between participants, but consistently in each RNA source. Such exons are thus stable phenotypes of the participant and may potentially become useful fingerprinting biomarkers. In agreement with previous studies, we found that each of the RNA sources is distinct. Unlike PAX and PBMC, LCL gene expression showed little association with the differential blood count. LCL, however, was able to detect two genes related to smoking status. PAX and PBMC identified Y-chromosome probe sets similarly and slightly better than LCL. PMID- 22045914 TI - Endometrial gene expression during early pregnancy differs between fertile and subfertile dairy cow strains. AB - A receptive uterine environment is a key component in determining a successful reproductive outcome. We tested the hypothesis that endometrial gene expression patterns differ in fertile and subfertile dairy cow strains. Twelve lactating dairy cattle of strains characterized as having fertile (n = 6) and subfertile (n = 6) phenotypes underwent embryo transfer on day 7 of the reproductive cycle. Caruncular and intercaruncular endometrial tissue was obtained at day 17 of pregnancy, and microarrays used to characterize transcriptional profiles. Statistical analysis of microarray data at day 17 of pregnancy revealed 482 and 1,021 differentially expressed transcripts (P value < 0.05) between fertile and subfertile dairy cow strains in intercaruncular and caruncular tissue, respectively. Functional analysis revealed enrichment for several pathways involved in key reproductive processes, including the immune response to pregnancy, luteolysis, and support of embryo growth and development, and in particular, regulation of histotroph composition. Genes implicated in the process of immune tolerance to the embryo were downregulated in subfertile cows, as were genes involved in preventing luteolysis and genes that promote embryo growth and development. This study provides strong evidence that the endometrial gene expression profile may contribute to the inferior reproductive performance of the subfertile dairy cow strain. PMID- 22045916 TI - A role for plant AURORA kinases in formative cell division. PMID- 22045915 TI - Tissue- and cell-type specific transcriptome profiling of expanding tomato fruit provides insights into metabolic and regulatory specialization and cuticle formation. AB - Tomato (Solanum lycopersicum) is the primary model for the study of fleshy fruits, and research in this species has elucidated many aspects of fruit physiology, development, and metabolism. However, most of these studies have involved homogenization of the fruit pericarp, with its many constituent cell types. Here, we describe the coupling of pyrosequencing technology with laser capture microdissection to characterize the transcriptomes of the five principal tissues of the pericarp from tomato fruits (outer and inner epidermal layers, collenchyma, parenchyma, and vascular tissues) at their maximal growth phase. A total of 20,976 high-quality expressed unigenes were identified, of which more than half were ubiquitous in their expression, while others were cell type specific or showed distinct expression patterns in specific tissues. The data provide new insights into the spatial distribution of many classes of regulatory and structural genes, including those involved in energy metabolism, source-sink relationships, secondary metabolite production, cell wall biology, and cuticle biogenesis. Finally, patterns of similar gene expression between tissues led to the characterization of a cuticle on the inner surface of the pericarp, demonstrating the utility of this approach as a platform for biological discovery. PMID- 22045917 TI - Arabidopsis alpha Aurora kinases function in formative cell division plane orientation. AB - To establish three-dimensional structures/organs, plant cells continuously have to adapt the orientation of their division plane in a highly regulated manner. However, mechanisms underlying switches in division plane orientation remain elusive. Here, we characterize a viable double knockdown mutant in Arabidopsis thaliana group alpha Aurora (AUR) kinases, AUR1 and AUR2, (aur1-2 aur2-2), with a primary defect in lateral root formation and outgrowth. Mutant analysis revealed that aur1-2 aur2-2 lateral root primordia are built from randomly oriented cell divisions instead of distinct cell layers. This phenotype could be traced back to cytokinesis defects and misoriented cell plates during the initial anticlinal pericycle cell divisions that give rise to lateral root primordia. Complementation assays showed that the Arabidopsis alpha group Aurora kinases are functionally divergent from the single beta group member AUR3 and that AUR1 functions in division plane orientation prior to cytokinesis. In addition to defective lateral root patterning, aur1-2 aur2-2 plants also show defects in orienting formative divisions during embryogenesis, divisions surrounding the main root stem cell niche, and divisions surrounding stomata formation. Taken together, our results put forward a central role for alpha Aurora kinases in regulating formative division plane orientation throughout development. PMID- 22045920 TI - Editorial: switching on arginase in M2 macrophages. PMID- 22045921 TI - Editorial: Neutrophil apoptosis: hot on the TRAIL of inflammatory resolution. PMID- 22045919 TI - Genome sequence of the white koji mold Aspergillus kawachii IFO 4308, used for brewing the Japanese distilled spirit shochu. AB - The filamentous fungus Aspergillus kawachii has traditionally been used for brewing the Japanese distilled spirit shochu. A. kawachii characteristically hyperproduces citric acid and a variety of polysaccharide glycoside hydrolases. Here the genome sequence of A. kawachii IFO 4308 was determined and annotated. Analysis of the sequence may provide insight into the properties of this fungus that make it superior for use in shochu production, leading to the further development of A. kawachii for industrial applications. PMID- 22045922 TI - The pea TCP transcription factor PsBRC1 acts downstream of Strigolactones to control shoot branching. AB - The function of PsBRC1, the pea (Pisum sativum) homolog of the maize (Zea mays) TEOSINTE BRANCHED1 and the Arabidopsis (Arabidopsis thaliana) BRANCHED1 (AtBRC1) genes, was investigated. The pea Psbrc1 mutant displays an increased shoot branching phenotype, is able to synthesize strigolactone (SL), and does not respond to SL application. The level of pleiotropy of the SL-deficient ramosus1 (rms1) mutant is higher than in the Psbrc1 mutant, rms1 exhibiting a relatively dwarf phenotype and more extensive branching at upper nodes. The PsBRC1 gene is mostly expressed in the axillary bud and is transcriptionally up-regulated by direct application of the synthetic SL GR24 and down-regulated by the cytokinin (CK) 6-benzylaminopurine. The results suggest that PsBRC1 may have a role in integrating SL and CK signals and that SLs act directly within the bud to regulate its outgrowth. However, the Psbrc1 mutant responds to 6 benzylaminopurine application and decapitation by increasing axillary bud length, implicating a PsBRC1-independent component of the CK response in sustained bud growth. In contrast to other SL-related mutants, the Psbrc1 mutation does not cause a decrease in the CK zeatin riboside in the xylem sap or a strong increase in RMS1 transcript levels, suggesting that the RMS2-dependent feedback is not activated in this mutant. Surprisingly, the double rms1 Psbrc1 mutant displays a strong increase in numbers of branches at cotyledonary nodes, whereas branching at upper nodes is not significantly higher than the branching in rms1. This phenotype indicates a localized regulation of branching at these nodes specific to pea. PMID- 22045923 TI - Localization and dynamics of nuclear speckles in plants. PMID- 22045924 TI - Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing induced heart failure. AB - AIMS: Recent studies indicate that brain natriuretic peptide (BNP(1-32)) may be truncated into BNP(3-32) by dipeptidyl peptidase IV (DPP4) and that BNP(3-32) has reduced biological activities compared with BNP(1-32). We investigated if DPP4 contributes to the cardiorenal alterations and to the attenuated response to BNP seen in heart failure. METHODS AND RESULTS: Haemodynamic and renal assessment was performed in 12 pigs at baseline, 4 weeks after pacing-induced heart failure, and during BNP infusion. They were randomized to either placebo or treatment with a DPP4 inhibitor, sitagliptin. After 4 weeks of pacing, heart rate was reduced compared with baseline in the sitagliptin group (60 +/- 2 vs. 95 +/- 16 b.p.m., P < 0.01), and an increase in stroke volume was observed in the sitagliptin group compared with placebo (+24 +/- 6% vs. -17 +/- 7%, P < 0.01). Glomerular filtration rate declined at week 4 compared with baseline in the placebo group (1.3 +/- 0.4 vs. 2.3 +/- 0.3 mL/kg/min, P < 0.01) but remained preserved in the sitagliptin group [1.8 +/- 0.2 vs. 2.0 +/- 0.3 mL/kg/min, P = NS (non significant)]. In the sitagliptin group, BNP infusion improved end-systolic elastance (68 +/- 5 vs. 31 +/- 4 mmHg/kg/mL, P < 0.05), ventricular-arterial coupling, and mechanical efficiency. Compared with controls (n = 6), myocardial gene expression of BNP, interleukin-6, Na(+)-Ca(2+) exchanger, and calmodulin was up-regulated in the placebo group, but not in the sitagliptin group. CONCLUSION: In pacing-induced heart failure, DPP4 inhibition preserves the glomerular filtration rate, modulates stroke volume and heart rate, and potentiates the positive inotropic effect of exogenous BNP at no energy expense. PMID- 22045925 TI - Effect of a telemonitoring-facilitated collaboration between general practitioner and heart failure clinic on mortality and rehospitalization rates in severe heart failure: the TEMA-HF 1 (TElemonitoring in the MAnagement of Heart Failure) study. AB - AIMS: Chronic heart failure (CHF) patients are frequently rehospitalized within 6 months after an episode of fluid retention. Rehospitalizations are preventable, but this requires an extensive organization of the healthcare system. In this study, we tested whether intensive follow-up of patients through a telemonitoring facilitated collaboration between general practitioners (GPs) and a heart failure clinic could reduce mortality and rehospitalization rate. METHODS AND RESULTS: One hunderd and sixty CHF patients [mean age 76 +/- 10 years, 104 males, mean left ventricular ejection fraction (LVEF) 35 +/- 15%] were block randomized by sealed envelopes and assigned to 6 months of intense follow-up facilitated by telemonitoring (TM) or usual care (UC). The TM group measured body weight, blood pressure, and heart rate on a daily basis with electronic devices that transferred the data automatically to an online database. Email alerts were sent to the GP and heart failure clinic to intervene when pre-defined limits were exceeded. All-cause mortality was significantly lower in the TM group as compared with the UC group (5% vs. 17.5%, P = 0.01). The total number of follow-up days lost to hospitalization, dialysis, or death was significantly lower in the TM group as compared with the UC group (13 vs. 30 days, P = 0.02). The number of hospitalizations for heart failure per patient showed a trend (0.24 vs. 0.42 hospitalizations/patient, P = 0.06) in favour of TM. CONCLUSION: Telemonitoring facilitated collaboration between GPs and a heart failure clinic reduces mortality and number of days lost to hospitalization, death, or dialysis in CHF patients. These findings need confirmation in a large trial. PMID- 22045926 TI - Complementary therapeutic effects of dual delivery of insulin-like growth factor 1 and vascular endothelial growth factor by gelatin microspheres in experimental heart failure. AB - AIMS: Strategies to prevent adverse left ventricular (LV) remodelling after myocardial infarction have included several traditional approaches and novel cell based or gene therapies. Delivery of growth factors in post-infarction heart failure has emerged as a valuable alternative strategy. Our aim was to investigate the effects of sequential release of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) from biodegradable gelatin microspheres in experimental heart failure. METHODS AND RESULTS: Gelatin hydrogel microspheres were known to guarantee a sustained release of encapsulated growth factors, characterized by an initial burst followed by a slower release. Rats with moderate myocardial infarction were randomized to receive empty microspheres (MI), microspheres loaded with IGF-1 or VEGF, or a combination thereof (DUAL). Myocardial injections of microspheres were performed at the time of surgery, and treatment lasted 4 weeks. Echocardiography, LV catheterization, morphometric histology and immunohistochemistry, and molecular assessment of downstream mediators [e.g. Akt, endothelial nitric oxide synthase (eNOS), and sarco/endoplasmic reticulum calcium ATPase-2 (SERCA-2)] were assessed at the end of the treatment period. Infarct sizes were 33 +/- 2, 28 +/- 4, 24 +/- 3, and 16 +/- 3% in the MI, IGF-1, VEGF, and DUAL groups, respectively. IGF-1 attenuated LV remodelling, improved LV systolic and diastolic function, increased myocyte size, and reduced apoptotic deaths, capillary loss, and indexes of inflammation. VEGF treated animals displayed a marked myocardial neoangiogenesis that led to the formation of mature vessels if combined with IGF-1 delivery. Downstream effects of IGF-1 were principally mediated by the Akt-mTOR (mammalian target of rapamycin)-dependent pathway, and both growth factors, particularly VEGF, induced a robust and sustained increase of eNOS. CONCLUSION: IGF-1 and VEGF exerted complementary therapeutic effects in post-infarction heart failure. Biodegradable gelatin microspheres provide sustained and controlled growth factor release locally, exposing myocardial tissue without the side effects of systemic administration. PMID- 22045927 TI - Genetic polymorphisms in carnitine palmitoyltransferase 1A gene are associated with variation in body composition and fasting lipid traits in Yup'ik Eskimos. AB - Variants of carnitine palmitoyltransferase 1A (CPT1A), a key hepatic lipid oxidation enzyme, may influence how fatty acid oxidation contributes to obesity and metabolic outcomes. CPT1A is regulated by diet, suggesting interactions between gene variants and diet may influence outcomes. The objective of this study was to test the association of CPT1A variants with body composition and lipids, mediated by consumption of polyunsaturated fatty acids (PUFA). Obesity phenotypes and fasting lipids were measured in a cross-sectional sample of Yup'ik Eskimo individuals (n = 1141) from the Center of Alaska Native Health Research (CANHR) study. Twenty-eight tagging CPT1A SNPs were evaluated with outcomes of interest in regression models accounting for family structure. Several CPT1A polymorphisms were associated with HDL-cholesterol and obesity phenotypes. The P479L (rs80356779) variant was associated with all obesity-related traits and fasting HDL-cholesterol. Interestingly, the association of P479L with HDL cholesterol was still significant after correcting for body mass index (BMI), percentage body fat (PBF), or waist circumference (WC). Our findings are consistent with the hypothesis that the L479 allele of the CPT1A P479L variant confers a selective advantage that is both cardioprotective (through increased HDL-cholesterol) and associated with reduced adiposity. PMID- 22045928 TI - Cholesterol esterification by ACAT2 is essential for efficient intestinal cholesterol absorption: evidence from thoracic lymph duct cannulation. AB - The hypothesis tested in this study was that cholesterol esterification by ACAT2 would increase cholesterol absorption efficiency by providing cholesteryl ester (CE) for incorporation into chylomicrons. The assumption was that absorption would be proportional to Acat2 gene dosage. Male ACAT2+/+, ACAT2+/-, and ACAT2-/- mice were fed a diet containing 20% of energy as palm oil with 0.2% (w/w) cholesterol. Cholesterol absorption efficiency was measured by fecal dual-isotope and thoracic lymph duct cannulation (TLDC) methods using [3H]sitosterol and [14C]cholesterol tracers. Excellent agreement among individual mice was found for cholesterol absorption measured by both techniques. Cholesterol absorption efficiency in ACAT2-/- mice was 16% compared with 46-47% in ACAT2+/+ and ACAT2+/- mice. Chylomicrons from ACAT2+/+ and ACAT2+/- mice carried ~80% of total sterol mass as CE, whereas ACAT2-/- chylomicrons carried >90% of sterol mass in the unesterified form. The total percentage of chylomicron mass as CE was reduced from 12% in the presence of ACAT2 to ~1% in ACAT2-/- mice. Altogether, the data demonstrate that ACAT2 increases cholesterol absorption efficiency by providing CE for chylomicron transport, but one copy of the Acat2 gene, providing ~50% of ACAT2 mRNA and enzyme activity, was as effective as two copies in promoting cholesterol absorption. PMID- 22045930 TI - Multi-site left ventricular pacing as a potential treatment for patients with postero-lateral scar: insights from cardiac magnetic resonance imaging and invasive haemodynamic assessment. AB - AIMS: Multi-site left ventricular (LV) pacing may be superior to single-site stimulation in correcting dyssynchrony and avoiding areas of myocardial scar. We sought to characterize myocardial scar using cardiac magnetic resonance imaging (CMR). We aimed to quantify the acute haemodynamic response to single-site and multi-site LV stimulation and to relate this to the position of the LV leads in relation to myocardial scar. METHODS: Twenty patients undergoing cardiac resynchronization therapy had implantation of two LV leads. One lead (LV1) was positioned in a postero-lateral vein, the second (LV2) in a separate coronary vein. LV dP/dtmax was recorded using a pressure wire during stimulation at LV1, LV2, and both sites simultaneously (LV1 + 2). Patients were deemed acute responders if DeltaLV dP/dtmax was >= 10%. Cardiac magnetic resonance imaging was performed to assess dyssynchrony as well as location and burden of scar. Scar anatomy was registered with fluoroscopy to assess LV lead position in relation to scar. RESULTS: LV dP/dtmax increased from 726 +/- 161 mmHg/s in intrinsic rhythm to 912 +/- 234 mmHg/s with LV1, 837 +/- 188 mmHg/s with LV2, and 932 +/- 201 mmHg/s with LV1 and LV2. Nine of 19 (47%) were acute responders with LV1 vs. 6/19 (32%) with LV2. Twelve of 19 (63%) were acute responders with simultaneous LV1 + 2. Two of three patients benefitting with multi-site pacing had the LV1 lead positioned in postero-lateral scar. CONCLUSION: Multi-site LV pacing increased acute response by 16% vs. single-site pacing. This was particularly beneficial in patients with postero-lateral scar identified on CMR. PMID- 22045929 TI - Biogenesis and functions of lipid droplets in plants: Thematic Review Series: Lipid Droplet Synthesis and Metabolism: from Yeast to Man. AB - The compartmentation of neutral lipids in plants is mostly associated with seed tissues, where triacylglycerols (TAGs) stored within lipid droplets (LDs) serve as an essential physiological energy and carbon reserve during postgerminative growth. However, some nonseed tissues, such as leaves, flowers and fruits, also synthesize and store TAGs, yet relatively little is known about the formation or function of LDs in these tissues. Characterization of LD-associated proteins, such as oleosins, caleosins, and sterol dehydrogenases (steroleosins), has revealed surprising features of LD function in plants, including stress responses, hormone signaling pathways, and various aspects of plant growth and development. Although oleosin and caleosin proteins are specific to plants, LD associated sterol dehydrogenases also are present in mammals, and in both plants and mammals these enzymes have been shown to be important in (steroid) hormone metabolism and signaling. In addition, several other proteins known to be important in LD biogenesis in yeasts and mammals are conserved in plants, suggesting that at least some aspects of LD biogenesis and/or function are evolutionarily conserved. PMID- 22045931 TI - How unique is continuity of care? A review of continuity and related concepts. AB - BACKGROUND: The concept of 'continuity of care' has changed over time and seems to be entangled with other care concepts, for example coordination and integration of care. These concepts may overlap, and differences between them often remain unclear. OBJECTIVE: In order to clarify the confusion of tongues and to identify core values of these patient-centred concepts, we provide a historical overview of continuity of care and four related concepts: coordination of care, integration of care, patient-centred care and case management. METHODS: We identified and reviewed articles including a definition of one of these concepts by performing an extensive literature search in PubMed. In addition, we checked the definition of these concepts in the Oxford English Dictionary. RESULTS: Definitions of continuity, coordination, integration, patient-centred care and case management vary over time. These concepts show both great entanglement and also demonstrate differences. Three major common themes could be identified within these concepts: personal relationship between patient and care provider, communication between providers and cooperation between providers. Most definitions of the concepts are formulated from the patient's perspective. CONCLUSIONS: The identified themes appear to be core elements of care to patients. Thus, it may be valuable to develop an instrument to measure these three common themes universally. In the patient-centred medical home, such an instrument might turn out to be an important quality measure, which will enable researchers and policy makers to compare care settings and practices and to evaluate new care interventions from the patient perspective. PMID- 22045932 TI - Later comes earlier, nowadays. PMID- 22045933 TI - Relapsing polychondritis-associated refractory airway stenosis. PMID- 22045934 TI - Longterm followup after tapering mycophenolate mofetil during maintenance treatment for proliferative lupus nephritis. PMID- 22045935 TI - Is posterior reversible encephalopathy syndrome underestimated in systemic lupus erythematosus? PMID- 22045936 TI - Significantly decreased serum 25-hydroxyvitamin d levels in a large german systemic sclerosis cohort. PMID- 22045937 TI - Differences in the incidence of microscopic polyangiitis and granulomatosis with polyangiitis (Wegener's). Is there a latitudinal gradient? PMID- 22045938 TI - Giant cell arteritis as a cause of acute myocarditis in the elderly. PMID- 22045939 TI - Great wits and madness: more near allied? AB - A purported association between creativity and psychopathology is ancient, persistent and controversial. Biographical research, studies of living artists and writers, and investigations into the cognitive and temperamental factors linked to both creativity and mood disorders suggest a more specific link to bipolar illness. A new, large and well-designed population-based study adds further support to this connection. PMID- 22045940 TI - Low serotonergic tone and elevated risk for substance misuse. AB - Cox et al's paper addresses an issue that has long been assumed to be a central aspect of brain function - the interplay of different neurotransmitters - but for which we have very little evidence so far. It is currently unclear whether these findings will have implications for the treatment of those with cocaine or other substance dependence. PMID- 22045941 TI - Overestimating patients' capacity. AB - Clinicians regularly overestimate patients' capacity to make decisions. This may jeopardise their autonomous decision-making. It may lead to poor clinical outcomes for patients and has potential adverse legal consequences for clinicians. There is a need to use the legal principles of the Mental Capacity Act more rigorously. PMID- 22045942 TI - Improving end-of-life care for people with dementia. AB - One in three adults over the age of 60 years will die with dementia. Most will have complex physical and psychological needs. Despite this, many people with dementia receive poor-quality end-of-life care. Recent government strategies have highlighted the importance of improved coordination and provision of services. PMID- 22045943 TI - A centenarian extraordinaire. AB - Henry Rollin, a distinguished Member, Fellow and now Honorary Fellow of the Royal College of Psychiatrists, has attained his 101st year. The achievements of this remarkable man are described and speculations made about the reasons for his longevity and his plans for the future. PMID- 22045944 TI - Predicting the development of schizophrenia in high-risk populations: systematic review of the predictive validity of prodromal criteria. AB - BACKGROUND: There is a great deal of debate on the usefulness and accuracy of prodromal criteria in predicting schizophrenia. The risk of treating people who screen false positive with medication is considerable. Yet intervening during the prodromal stage of illness may reduce the burden caused by schizophrenia. AIMS: To draw together the evidence base for the predictive validity of prodromal criteria in identifying individuals at high risk of developing schizophrenia. METHOD: We conducted a systematic review of prospective studies investigating the predictive validity of prodromal criteria in schizophrenia. RESULTS: Our study found two main criteria, ultra-high-risk criteria and basic-symptoms criteria, used in studies investigating the predictive validity of prodromal symptoms. The sensitivity and specificity of ultra-high-risk criteria was 0.81 (95% CI 0.76 0.85) and 0.67 (95% CI 0.64-0.70) respectively and for basic-symptoms criteria sensitivity and specificity was 0.97 (95% CI 0.91-1.00) and 0.59 (95% CI 0.48 0.70) respectively. CONCLUSIONS: Both ultra-high-risk criteria and basic-symptoms criteria are useful in predicting the development of schizophrenia among high risk populations. PMID- 22045945 TI - Biogenetic explanations and public acceptance of mental illness: systematic review of population studies. AB - BACKGROUND: Biological or genetic models of mental illness are commonly expected to increase tolerance towards people with mental illness, by reducing notions of responsibility and blame. AIMS: To investigate whether biogenetic causal attributions of mental illness among the general public are associated with more tolerant attitudes, whether such attributions are related to lower perceptions of guilt and responsibility, to what extent notions of responsibility are associated with rejection of people who are mentally ill, and how prevalent notions of responsibility are among the general public with regard to different mental disorders. METHOD: A systematic review was conducted of representative population studies examining attitudes towards people with mental illness and beliefs about such disorders. RESULTS: We identified 33 studies relevant to this review. Generally, biogenetic causal attributions were not associated with more tolerant attitudes; they were related to stronger rejection in most studies examining schizophrenia. No published study reported on associations of biogenetic causal attributions and perceived responsibility. The stereotype of self-responsibility was unrelated to rejection in most studies. Public images of mental disorder are generally dominated by the stereotypes of unpredictability and dangerousness, whereas responsibility is less relevant. CONCLUSIONS: Biogenetic causal models are an inappropriate means of reducing rejection of people with mental illness. PMID- 22045947 TI - Persistent distress after psychological exposure to the Nagasaki atomic bomb explosion. AB - BACKGROUND: Although there is speculation that individuals living in the vicinity of nuclear disasters have persistent mental health deterioration due to psychological stress, few attempts have been made to examine this issue. AIMS: To determine whether having been in the vicinity of the Nagasaki atomic bomb explosion in the absence of substantial exposure to radiation affected the mental health of local inhabitants more than half a century later. METHOD: Participants were randomly recruited from individuals who lived in the vicinity of the atomic bomb explosion in uncontaminated suburbs of Nagasaki. This sample (n = 347) was stratified by gender, age, perception of the explosion and current district of residence. Controls (n = 288) were recruited from among individuals who had moved into the area from outside Nagasaki 5-15 years after the bombing, matched for gender, age and district of residence. The primary outcome measure was the proportion of those at high risk of mental disorder based on the 28-item version of the General Health Questionnaire, with a cut-off point of 5/6. Other parameters related to individual perception of the explosion, health status, life events and habits were also assessed. RESULTS: Having been in the vicinity of the explosion was the most significant factor (OR = 5.26, 95% CI 2.56-11.11) contributing to poorer mental health; erroneous knowledge of radiological hazard showed a mild association. In the sample group, anxiety after learning of the potential radiological hazard was significantly correlated with poor mental health (P<0.05), whereas anxiety about the explosion, or the degree of perception of it, was not; 74.5% of the sample group believed erroneously that the flash of the explosion was synonymous with radiation. CONCLUSIONS: Having been in the vicinity of the atomic bomb explosion without radiological exposure continued to be associated with poorer mental health more than half a century after the event. Fear on learning about the potential radiological hazard and lack of knowledge about radiological risk are responsible for this association. PMID- 22045946 TI - Clinical and cognitive characteristics of children with attention-deficit hyperactivity disorder, with and without copy number variants. AB - BACKGROUND: Submicroscopic, rare chromosomal copy number variants (CNVs) contribute to neurodevelopmental disorders but it is not known whether they define atypical clinical cases. AIMS: To identify whether large, rare CNVs in attention-deficit hyperactivity disorder (ADHD) are confined to a distinct clinical subgroup. METHOD: A total of 567 children with ADHD aged 5-17 years were recruited from community clinics. Psychopathology was assessed using the Child and Adolescent Psychiatric Assessment. Large, rare CNVs (>500 kb, <1% frequency) were defined from single nucleotide polymorphism data. RESULTS: Copy number variant carriers (13.6%) showed no differences from non-carriers in ADHD symptom severity, symptom type, comorbidity, developmental features, family history or pre-/perinatal markers. The only significant difference was a higher rate of intellectual disability (24% v. 9%, chi(2) = 15.5, P = 0.001). Most CNV carriers did not have intellectual disability. CONCLUSIONS: Large, rare CNVs are not restricted to an atypical form of ADHD but may be more highly enriched in children with cognitive problems. PMID- 22045948 TI - Effectiveness of Australian youth suicide prevention initiatives. AB - BACKGROUND: After an epidemic rise in Australian young male suicide rates over the 1970s to 1990s, the period following the implementation of the original National Youth Suicide Prevention Strategy (NYSPS) in 1995 saw substantial declines in suicide in young men. AIMS: To investigate whether areas with locally targeted suicide prevention activity implemented after 1995 experienced lower rates of young adult suicide, compared with areas without such activity. METHOD: Localities with or without identified suicide prevention activity were compared during the period of the NYSPS implementation (1995-1998) and a period subsequent to implementation (1999-2002) to establish whether annual average suicide rates were lower and declined more quickly in areas with suicide prevention activity over the period 1995-2002. RESULTS: Male suicide rates were lower in areas with targeted suicide prevention activity (and higher levels of funding) compared with areas receiving no activity both during (RR = 0.89, 95% CI 0.80-0.99, P = 0.030) and after (RR = 0.86, 95% CI 0.77-0.96, P = 0.009) implementation, with rates declining faster in areas with targeted activity than in those without (13% v. 10% decline). However, these differences were reduced and were no longer statistically significant following adjustment for sociodemographic variables. There was no difference in female suicide rates between areas with or without targeted suicide prevention activity. CONCLUSIONS: There was little discernible impact on suicide rates in areas receiving locally targeted suicide prevention activities in the period following the NYSPS. PMID- 22045949 TI - Early intervention in anorexia nervosa. PMID- 22045950 TI - Accuracy of death certification. PMID- 22045951 TI - Abortion and mental health. PMID- 22045952 TI - Multistage evaluation and commissioning of a pre-calibrated, single-use OneDosePlus MOSFET system for in vivo dosimetry in a radiotherapy department. AB - OBJECTIVES: The aim was to determine the agreement between absorbed dose measurements using the OneDosePlus and treatment planning system calculations in ideal circumstances, minimising patient-related uncertainties, before deciding upon action levels. METHODS: A OneDose metal oxide semiconductor field-effect transistor (Sicel Technologies, Morrisville, NC) in vivo dosimetry system was subjected to a multistage evaluation that tested standard and non-standard field conditions related to treatment planning system calculations for an anthropomorphic phantom. RESULTS: The system was found to perform within manufacturer specifications. Batch uniformity was found to be within specification when measured using a method described by Halvorsen. A modification used to assess statistical distribution of response showed an increase in the value of two standard deviations (2 sigma) from +/- 2.3 to +/- 2.9%, which was still within the manufacturer-stated value of +/- 5%. The tests using the anthropomorphic phantom also emphasised the fact that patient density inhomogeneities in the region of the D(max) point will affect the dose calculated by the treatment planning system and delivered to the patient. CONCLUSION: The OneDose system does not account for these inhomogeneities, leading to dependence in the deviation between expected and reported dose on inhomogeneity and choice of calculation algorithm. PMID- 22045954 TI - Institutional requirements for influenza vaccination of healthcare personnel: results from a nationally representative survey of acute care hospitals--United States, 2011. AB - BACKGROUND: Many health professional organizations now endorse influenza vaccination as a condition of employment in healthcare settings. Our objective was to describe institutional requirements for influenza vaccination of healthcare personnel (HCP) among US hospitals during the 2010-2011 influenza season. METHODS: A survey was mailed in 2011 to a nationally representative sample of 998 acute care hospitals. An institutional requirement was defined as "a policy that requires HCP to receive or decline influenza vaccination, with or without consequences for vaccine refusal." A weighted analysis included univariate analyses and logistic regression. RESULTS: Of responding hospitals (n = 808; 81.0%), 440 (55.6%) reported institutional requirements for influenza vaccination. Although employees were uniformly subject to requirements, nonemployees often were not. The proportion of requirements with consequences for vaccine refusal was 44.4% (n = 194); where consequences were imposed, nonmedical exemptions were often granted (69.3%). Wearing a mask was the most common consequence (74.2% of 194 requirements); by contrast, 29 hospitals (14.4%) terminated unvaccinated HCP. After adjustment for demographic factors, the following characteristics remained significantly associated with requirements: location in a state requiring HCP to receive or decline influenza vaccine, caring for inpatients that are potentially vulnerable to influenza, use of >=9 Advisory Committee on Immunization Practices-recommended, evidence-based influenza vaccination campaign strategies, and for-profit ownership. CONCLUSIONS: Influenza vaccination requirements were prevalent among hospitals of varying size and location. However, few policies were as stringent or as comprehensive as those endorsed by health professional organizations. Because influenza vaccination requirements are a viable alternative for hospitals unable to achieve high coverage through voluntary policies, there is still substantial room for improvement. PMID- 22045953 TI - Automatic vs semi-automatic global cardiac function assessment using 64-row CT. AB - OBJECTIVE: Global cardiac function assessment using multidetector CT (MDCT) is time-consuming. Therefore we sought to compare an automatic software tool with an established semi-automatic method. METHODS: A total of 36 patients underwent CT with 64 * 0.5 mm detector collimation, and global left ventricular function was subsequently assessed by two independent blinded readers using both an automatic region-growing-based software tool (with and without manual adjustment) and an established semi-automatic software tool. We also analysed automatic motion mapping to identify end-systole. RESULTS: The time needed for assessment using the semi-automatic approach (12:12 +/- 6:19 min) was reduced by 75-85% with the automatic software tool (unadjusted, 01:34 +/- 0:29 min, adjusted, 02:53 +/- 1:19 min; both p<0.001). There was good correlation (r=0.89; p<0.001) for the ejection fraction (EF) between the adjusted automatic (58.6 +/- 14.9%) and the semi automatic (58.0 +/- 15.3%) approaches. Also the manually adjusted automatic approach led to significantly smaller limits of agreement than the unadjusted automatic approach for end-diastolic volume (+/-36.4 ml vs +/-58.5 ml, p>0.05). Using motion mapping to automatically identify end-systole reduced analysis time by 95% compared with the semi-automatic approach, but showed inferior precision for EF and end-systolic volume. CONCLUSION: Automatic function assessment using MDCT with manual adjustment shows good agreement with an established semi automatic approach, while reducing the analysis by 75% to less than 3 min. This suggests that automatic CT function assessment with manual correction may be used for fast, comfortable and reliable evaluation of global left ventricular function. PMID- 22045955 TI - Treatment of refractory coccidioidomycosis with voriconazole or posaconazole. AB - BACKGROUND: Coccidioidomycosis is a fungal infection of the desert southwestern United States. It may be self-limited or may require antifungal therapy. Currently used triazoles (eg, fluconazole and itraconazole) have largely supplanted amphotericin B, which is fraught with adverse effects. Limited case reports and small open-label trials show that voriconazole and posaconazole benefit patients with coccidioidomycosis refractory to first-line agents. METHODS: We conducted a retrospective review of patients prescribed voriconazole or posaconazole for coccidioidomycosis at our institution between 1 January 2006 and 1 August 2010. Outcomes were assessed with both a retrospectively applied Mycosis Study Group score (ie, a composite score for symptoms, serology, and radiographic findings) and the documented impressions of treating medical practitioners. RESULTS: Twenty-one patients who received voriconazole and 16 who received posaconazole met study criteria. After a median duration of 6 months of voriconazole treatment, 14 of 21 patients (67%) were improved in overall status, 5 were unchanged, and 2 were unresponsive to voriconazole. After a median of 17 months of posaconazole treatment, 12 of 16 patients (75%) showed improvement, 1 was unchanged, and 3 were unresponsive due to medication intolerance or relapsed infection. CONCLUSIONS: Voriconazole and posaconazole are reasonable but not infallible options for salvage treatment of refractory coccidioidomycosis. Prospective comparative trials are required to provide further insights into their efficacy and utility. PMID- 22045957 TI - A man with Fever, gingival plaque, and diffuse lymphadenopathy. PMID- 22045968 TI - Angiographic disease progression and residual risk of cardiovascular events while on optimal medical therapy: observations from the COURAGE Trial. AB - BACKGROUND: The extent to which recurrent events in patients with stable coronary artery disease is attributable to progression of an index lesion originally >=50% diameter stenosis (DS) but not revascularized or originally <50% DS is unknown during optimal medical therapy (OMT). METHODS AND RESULTS: In the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 205 patients assigned to OMT plus percutaneous coronary intervention (PCI) and 284 patients assigned to OMT only had symptom-driven angiograms suitable for analysis. Percentages of patients in the OMT+PCI and OMT-only cohorts with index lesions originally <50% DS were 30% and 32%, respectively; 20% and 68% had index lesions originally >=50% DS. In both groups, index lesions originally <50% or >=50% DS represented <4% and <25% of all such lesions, respectively. The only angiographic predictor of myocardial infarction or acute coronary syndrome was the number of lesions originally >=50% DS that had not been revascularized (odds ratio, 1.15; confidence limits, 1.01-1.31; P<0.04). CONCLUSIONS: Lesions originally <50% DS were index lesions in one third of patients referred for symptom-driven repeat angiography, but represented <4% of all such lesions. Nonrevascularized lesions originally >=50% DS were more often index lesions in OMT-only patients, but still represented a minority (<25%) of all such lesions. These findings underscore the need for improved therapies to arrest plaque progression and reliable strategies for selecting stenoses warranting PCI. PMID- 22045969 TI - Comprehensive intravascular ultrasound assessment of stent area and its impact on restenosis and adverse cardiac events in 403 patients with unprotected left main disease. AB - BACKGROUND: We assessed the optimal intravascular ultrasound (IVUS) stent area to predict angiographic in-stent restenosis (ISR) after sirolimus-eluting stent implantation for unprotected left main coronary artery (LM) disease. METHODS AND RESULTS: A total of 403 patients treated with single- or 2-stent strategies (crushing and T-stent) had immediate poststenting IVUS and 9-month follow-up angiography. Poststenting minimal stent area (MSA) was measured in each of 4 segments: ostial left anterior descending (LAD), ostial left circumflex (LCX) polygon of confluence (POC, confluence zone of LAD and LCX), and proximal LM above the POC. Overall, 46 (11.4%) showed angiographic restenosis at 9 months: 3 of 67 (4.5%) nonbifurcation lesions treated with a single-stent, 14 of 222 (6.3%) bifurcation lesions treated with single-stent crossover, and 29 of 114 (25.4%) of bifurcation lesions treated with 2 stents. The MSA cutoffs that best predicted ISR on a segmental basis were 5.0 mm(2) (ostial LCX ISR), 6.3 mm(2) (ostial LAD ISR), 7.2 mm(2) (ISR within the POC), and 8.2 mm(2) (ISR within the LM above the POC). Using these criteria, 133 (33.8%) had underexpansion of at least 1 segment. Angiographic ISR (at any location) was more frequent in lesions with underexpansion of at least 1 segment versus lesions with no underexpansion (24.1% versus 5.4%, P<0.001). Two-year major adverse coronary event-free survival rate was significantly lower in patients with underexpansion of at least 1 segment versus lesions with no underexpansion (90+/-3% versus 98+/-1%, log-rank P<0.001), and poststenting underexpansion was an independent predictor for major adverse cardiac events (adjusted hazard ratio, 5.56; 95% confidence interval, 1.99-15.49; P=0.001). CONCLUSIONS: With these criteria, IVUS optimization during LMCA stenting procedures may improve clinical outcomes. PMID- 22045970 TI - Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in East Asian acute myocardial infarction survivors treated with clopidogrel and aspirin. AB - BACKGROUND: As compared with whites, East Asians more often carry the cytochrome P450 (CYP) 2C19 loss-of-function (LOF) allele with the CYP2C19*3 variant. The influence of the CYP2C19 LOF alleles (*2 and *3) on clopidogrel response and clinical outcomes in East Asians with acute myocardial infarction (AMI) has not been reported. We sought to evaluate the effect of the CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in these patients. METHODS AND RESULTS: Patients who survived an AMI (n=266) were enrolled in a single center registry. Predischarge platelet reactivity was assessed with light transmittance aggregometry and the VerifyNow P2Y12 assay; the CYP2C19*2, *3, *17 and ABCB1 3435C>T variants were determined. The primary clinical end point was the composite of cardiovascular death, nonfatal MI, and ischemic stroke. The median exposure to clopidogrel was 21 months (interquartile range, 13-29). The ABCB1 3435C>T was not related to clopidogrel response or cardiovascular events. Carriage of the CYP2C19 LOF variant allele was relatively high (60.9%, n=162; *2/*17=2, *3/*17=1, *1/*2=96, *1/*3=29, *2/*2=20, and *2/*3=14). Platelet reactivity increased proportionally according to the number of the CYP2C19 LOF alleles. In a multivariate regression analysis, the risk of high on-treatment platelet reactivity (HPR) increased depending on the number of CYP2C19 LOF allele [1 LOF allele; odds ratio (OR), 1.8; 95% confidence interval (CI), 0.8 to 4.2, P=0.152; and 2 LOF alleles; OR, 2.8; 95% CI, 1.2 to 6.5; P=0.016]; platelet reactivity and the rate of HPR did not differ between the CYP2C19*2 versus *3 allele carriage. In addition, cardiovascular event occurrence increased according to the number of the CYP2C19 LOF allele; compared with noncarriers, carriers of 1 [hazard ratio (HR), 3.1; 95% CI, 0.8 to 11.6; P=0.089] and 2 CYP2C19 LOF allele(s) (HR, 10.1; 95% CI, 1.8-58.8; P=0.008) were associated with clinical end point. The clinical impact of the CYP2C19*2 versus *3 allele carriage also did not differ. CONCLUSIONS: Among East Asian patients who survived an AMI, the CYP2C19 LOF allele carriage appears to affect clopidogrel pharmacodynamics and cardiovascular events according to the number of the CYP2C19 LOF allele; the influence of the CYP2C19*2 and *3 alleles on clopidogrel response and long-term outcomes does not differ. PMID- 22045971 TI - From bedside to bench: the effect of quality of life on the immune system and the effect of the immune system on quality of life. PMID- 22045972 TI - Validity of quality of life measurement tools--from generic to disease-specific. AB - Health-related quality of life (HRQOL) is an important measure of a patient's perception of his/her illness. Over the past 3 decades, numerous instruments have been developed to measure HRQOL in various patient populations, with 2 basic approaches: generic and disease-specific. While generic measures have broad application across different types and severity of diseases, disease-specific measures are designed to assess particular diseases or patient populations. All HRQOL instruments, however, must be valid and have high reliability and responsiveness. Validity ensures that the instrument measures what it is supposed to measure. Reliable instruments are able to reproducibly differentiate between subjects. Responsive evaluative measures are able to detect important changes in HRQOL during a period of time, even if those changes are small. HRQOL measures should also be interpretable, meaning that the differences in scores that correspond to small, moderate, and large HRQOL changes are easily identifiable. This article describes the steps in the development of HRQOL instruments from the conceptual framework to creation and testing. Several examples of generic and disease-specific instruments commonly used to evaluate HRQOL in patients with immune-mediated inflammatory diseases (IMID) are provided. PMID- 22045973 TI - Quality of life in patients with immune-mediated inflammatory diseases. AB - There is no doubt that patients with immune-mediated inflammatory diseases (IMID) have a significantly impaired quality of life (QOL). Pain and disability often leave these patients helpless and frustrated. The recognition that addressing physical and psychological functioning plays a significant role in an overall treatment approach led to the inclusion of QOL measures as secondary outcomes in clinical trials with IMID patients. To that end, both generic and disease specific instruments have been utilized. Measurement of health-related QOL (HRQOL) and patient-reported outcomes (PRO) in a controlled manner allows for better understanding of the correlation between different aspects of disease activity and QOL. In addition, the effects of different therapeutic options on HRQOL-related outcomes can be further evaluated. This 3-part section describes key QOL-related complaints of patients with IMID affecting joints, skin, or gut. An overview of the strengths and weaknesses of various commonly used HRQOL instruments is provided. Finally, the influence of anti-tumor necrosis factor alpha agents on HRQOL outcomes, as assessed in recent clinical trials, is highlighted. PMID- 22045974 TI - Quality of life issues in pediatric immune-mediated inflammatory disease. AB - It has been well established that children with a chronic disease, including those with inflammatory bowel disease (IBD) and juvenile idiopathic arthritis (JIA), report lower health-related quality of life (HRQOL) as compared to their healthy peers. Over the past 20 years there has been a significant emphasis on the development of measures of function and HRQOL for application in JIA and pediatric IBD. Several of the instruments currently used to assess HRQOL in children with immune-mediated inflammatory diseases (IMID), including the Juvenile Arthritis Quality of Life Questionnaire (JAQQ) and IMPACT questionnaire for pediatric IBD, were developed and validated by Canadian-based research teams. This review describes several disease-specific and generic instruments used to assess QOL in children with IBD or JIA. It also provides an overview of findings from several outcomes studies that applied the described tools in assessing HRQOL in children and adolescents with these conditions. PMID- 22045975 TI - The influence of uveitis on patients with immune-mediated inflammatory disease. AB - Uveitis, defined as an intraocular inflammatory disease, is one of the main causes of visual impairment in the working-age population. The condition often coexists with other immune-mediated inflammatory diseases (IMID) and greatly contributes to reduced quality of life (QOL) in affected individuals. While visual acuity remains the most commonly used measure of visual function in patients with uveitis, the US National Eye Institute Visual Function Questionnaire is frequently used to assess their health-related QOL. However, despite intuition that coexisting uveitis might exaggerate already impaired QOL in patients with IMID, specific questions related to their visual functioning are rarely included in clinical trials or assessed in daily practice. We provide an overview of the occurrence and significance of uveitis in patients with IMID, its consequences, and the role of tumor necrosis factor-alpha inhibitors in overall treatment approaches. PMID- 22045976 TI - Psychiatric disorders in patients with immune-mediated inflammatory diseases: prevalence, association with disease activity, and overall patient well-being. AB - There has been much speculation on the importance of emotional factors in patients with immune-mediated inflammatory disease (IMID); it is only in the past 10 years that well designed, large-cohort studies have been able to clarify this relationship. This article provides an overview of evidence on the occurrence of depression and anxiety in IMID, and the role of these comorbidities as risk factors for onset of IMID, as well as the degree to which they affect the course of disease and treatment outcomes. PMID- 22045977 TI - Fatigue and quality of sleep in patients with immune-mediated inflammatory disease. AB - Fatigue, a systemic feeling of exhaustion, is a common symptom of many chronic illnesses, including immune-mediated inflammatory diseases (IMID). IMID-related fatigue is associated with disease activity and pain and has detrimental effects on patient quality of life and overall well-being. Thus, routine assessment and management of fatigue in clinical practice is important. This article provides an overview of the prevalence, correlates, and predictors of fatigue in IMID. There is also discussion of the effects of different treatments on fatigue outcomes, as well as management recommendations. PMID- 22045978 TI - The influence of stress on the development and severity of immune-mediated diseases. AB - Evidence that psychological stress can increase inflammation and worsen the course of immune-mediated inflammatory disease (IMID) is steadily accumulating. The majority of data supporting this hypothesis come from studies in patients with inflammatory bowel disease (IBD). While there is no evidence to suggest that stress is a primary cause of IBD, many, although not all, studies have found that patients with IBD experience increased stress and stressful life events before disease exacerbations. Further, the disease itself can cause psychological stress, creating a vicious cycle. In addition to reviewing the epidemiological evidence supporting a stress-IMID relationship, this article also briefly discusses how stress-related changes in neural, endocrine, and immune functioning may contribute to the pathogenesis of immune diseases, IBD in particular. The effects of different pharmacological and nonpharmacological interventions, including stress management and behavioral therapy, on stress, mood, quality of life (QOL), and activity of the underlying IMID are also summarized. PMID- 22045979 TI - The role of inflammation in the pathophysiology of depression: different treatments and their effects. AB - Compelling evidence suggests that inflammation contributes to the development of depression. Many depressed individuals have higher levels of proinflammatory mediators, which appear to interact with many of the pathophysiological domains of depression, including neuroendocrine function, neurotransmitter metabolism, and synaptic plasticity. This is further supported by observation that therapeutic administration of interferon-alpha (IFN-alpha) leads to depression in a significant proportion of patients. These findings suggest that targeting proinflammatory cytokines and their signaling pathways may represent a unique therapeutic opportunity to treat depression and related conditions, such as labile anger, irritability, and fatigue. PMID- 22045980 TI - Socioeconomic burden of immune-mediated inflammatory diseases--focusing on work productivity and disability. AB - Chronic disabling conditions, such as immune-mediated inflammatory diseases (IMID), adversely affect patients in terms of physical suffering and pain, impaired function, and diminished quality of life. These persistent relapsing diseases have a significant influence on individual employment status and work related productivity. In addition to the significant burden on patients and their families, IMID represent a sizable burden to society due to high healthcare and non-healthcare related costs. Non-healthcare related, or indirect, costs - primarily associated with decreased work productivity, disability payments, and early retirements - are typically greater contributors than direct healthcare costs to the total costs associated with IMID. This article discusses the socioeconomic impact of several IMID, including rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, and psoriasis. PMID- 22045981 TI - Summing up: quality of life in chronic immune-mediated inflammatory diseases. AB - A series of reports is summarized in which measurement of quality of life (QOL) in various immune-mediated inflammatory diseases (IMID), the parameters that contribute to QOL, and the interrelationship between inflammatory diseases in specific organ systems and psychosocial domains are explored. Current treatment trials in IMID include QOL measures, particularly clinical trials of biologic therapy. There is increasing evidence that several available therapies benefit QOL. Among the factors that contribute to QOL, fatigue, depression, and stress are common and deserve attention from clinicians managing these patients. PMID- 22045982 TI - Ribosomal protein gene deletions in Diamond-Blackfan anemia. AB - Diamond-Blackfan anemia (DBA) is a congenital BM failure syndrome characterized by hypoproliferative anemia, associated physical abnormalities, and a predisposition to cancer. Perturbations of the ribosome appear to be critically important in DBA; alterations in 9 different ribosomal protein genes have been identified in multiple unrelated families, along with rarer abnormalities of additional ribosomal proteins. However, at present, only 50% to 60% of patients have an identifiable genetic lesion by ribosomal protein gene sequencing. Using genome-wide single-nucleotide polymorphism array to evaluate for regions of recurrent copy variation, we identified deletions at known DBA-related ribosomal protein gene loci in 17% (9 of 51) of patients without an identifiable mutation, including RPS19, RPS17, RPS26, and RPL35A. No recurrent regions of copy variation at novel loci were identified. Because RPS17 is a duplicated gene with 4 copies in a diploid genome, we demonstrate haploinsufficient RPS17 expression and a small subunit ribosomal RNA processing abnormality in patients harboring RPS17 deletions. Finally, we report the novel identification of variable mosaic loss involving known DBA gene regions in 3 patients from 2 kindreds. These data suggest that ribosomal protein gene deletion is more common than previously suspected and should be considered a component of the initial genetic evaluation in cases of suspected DBA. PMID- 22045983 TI - Defining the role of TORC1/2 in multiple myeloma. AB - Mammalian target of rapamycin (mTOR) is a downstream serine/threonine kinase of the PI3K/Akt pathway that integrates signals from the tumor microenvironment to regulate multiple cellular processes. Rapamycin and its analogs have not shown significant activity in multiple myeloma (MM), likely because of the lack of inhibition of TORC2. In the present study, we investigated the baseline activity of the PI3K/Akt/mTOR pathway TORC1/2 in MM cell lines with different genetic abnormalities. TORC1/2 knock-down led to significant inhibition of the proliferation of MM cells, even in the presence of BM stromal cells. We also tested INK128, a dual TORC1/2 inhibitor, as a new therapeutic agent against these MM cell lines. We showed that dual TORC1/2 inhibition is much more active than TORC1 inhibition alone (rapamycin), even in the presence of cytokines or stromal cells. In vitro and in vivo studies showed that p-4EBP1 and p-Akt inhibition could be predictive markers of TORC2 inhibition in MM cell lines. Dual TORC1/2 inhibition showed better inhibition of adhesion to BM microenvironmental cells and inhibition of homing in vivo. These studies form the basis for further clinical testing of TORC1/2 inhibitors in MM. PMID- 22045984 TI - Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis. AB - Vascular injury initiates rapid platelet activation that is critical for hemostasis, but it also may cause thrombotic diseases, such as myocardial infarction or ischemic stroke. Reorganizations of the platelet cytoskeleton are crucial for platelet shape change and secretion and are thought to involve activation of the small GTPase RhoA. In this study, we analyzed the in vitro and in vivo consequences of megakaryocyte- and platelet-specific RhoA gene deletion in mice. We found a pronounced macrothrombocytopenia in RhoA-deficient mice, with platelet counts of approximately half that of wild-type controls. The mutant cells displayed an altered shape but only a moderately reduced life span. Shape change of RhoA-deficient platelets in response to G(13)-coupled agonists was abolished, and it was impaired in response to G(q) stimulation. Similarly, RhoA was required for efficient secretion of alpha and dense granules downstream of G(13) and G(q). Furthermore, RhoA was essential for integrin-mediated clot retraction but not for actomyosin rearrangements and spreading of activated platelets on fibrinogen. In vivo, RhoA deficiency resulted in markedly prolonged tail bleeding times but also significant protection in different models of arterial thrombosis and in a model of ischemic stroke. Together, these results establish RhoA as an important regulator of platelet function in thrombosis and hemostasis. PMID- 22045985 TI - Control of Plasmodium falciparum erythrocytic cycle: gammadelta T cells target the red blood cell-invasive merozoites. AB - The control of Plasmodium falciparum erythrocytic parasite density is essential for protection against malaria, because it prevents pathogenesis and progression toward severe disease. P falciparum blood-stage parasite cultures are inhibited by human Vgamma9Vdelta2 gammadelta T cells, but the underlying mechanism remains poorly understood. Here, we show that both intraerythrocytic parasites and the extracellular red blood cell-invasive merozoites specifically activate Vgamma9Vdelta2 T cells in a gammadelta T cell receptor-dependent manner and trigger their degranulation. In contrast, the gammadelta T cell-mediated antiparasitic activity only targets the extracellular merozoites. Using perforin deficient and granulysin-silenced T-cell lines, we demonstrate that granulysin is essential for the in vitro antiplasmodial process, whereas perforin is dispensable. Patients infected with P falciparum exhibited elevated granulysin plasma levels associated with high levels of granulysin-expressing Vdelta2(+) T cells endowed with parasite-specific degranulation capacity. This indicates in vivo activation of Vgamma9Vdelta2 T cells along with granulysin triggering and discharge during primary acute falciparum malaria. Altogether, this work identifies Vgamma9Vdelta2 T cells as unconventional immune effectors targeting the red blood cell-invasive extracellular P falciparum merozoites and opens novel perspectives for immune interventions harnessing the antiparasitic activity of Vgamma9Vdelta2 T cells to control parasite density in malaria patients. PMID- 22045986 TI - In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study. AB - We have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8(+) T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25(+), Foxp3(+) T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100(+), CD1a(+) dendritic cells. There was a trend toward greater reduction of CD25(+) T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993. PMID- 22045987 TI - Restricted Kaposi's sarcoma (KS) herpesvirus transcription in KS lesions from patients on successful antiretroviral therapy. AB - Kaposi's sarcoma (KS) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8). KS is an AIDS-defining cancer, and it is changing in the post-antiretroviral therapy (post-ART) era. In countries with ready access to ART, approximately one-third of KS cases present in patients with undetectable HIV loads and CD4 counts of >=200 cells/ul. This is in contrast to pre-ART era KS, which was associated with systemic HIV replication and CD4 counts of <=200 cells/ul. Using primary patient biopsy specimens, we identified a novel molecular signature that characterizes AIDS KS lesions that develop in HIV-suppressed patients on ART: KSHV transcription is limited in HIV-suppressed patients. With one exception, only the canonical viral latency mRNAs were detectable. In contrast, early AIDS KS lesions expressed many more viral mRNAs, including, for instance, the viral G protein-coupled receptor (vGPCR). IMPORTANCE: This is the first genomewide study of Kaposi's sarcoma-associated herpesvirus (KSHV) transcription in KS lesions in the post-antiretroviral (post-ART) era. It shows that the gene expression of KSHV is altered in patients on ART, and it provides clinical evidence for active AIDS (as characterized by high HIV load and low CD4 counts) being a potential modulator of KSHV transcription. This implies a novel mode of pathogenesis (tightly latent KS), which may inform KS cancer treatment options in the post-ART era. PMID- 22045988 TI - Reciprocal regulation of cephalosporin resistance in Enterococcus faecalis. AB - Antibiotic-resistant enterococci are major causes of hospital-acquired infections and therefore represent a serious public health problem. One well-known risk factor for the acquisition of hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporin antibiotics. Enterococci can proliferate in patients undergoing cephalosporin therapy due to intrinsic cephalosporin resistance, a characteristic of the genus Enterococcus. However, the molecular basis for cephalosporin resistance in E. faecalis has yet to be adequately elucidated. Previously we determined that a putative Ser/Thr kinase, IreK (formerly PrkC), is required for intrinsic cephalosporin resistance in E. faecalis. Here we show that kinase activity is required for cephalosporin resistance and, further, that resistance in E. faecalis is reciprocally regulated by IreK and IreP, a PP2C-type protein phosphatase encoded immediately upstream of IreK. Mutants of two divergent lineages of E. faecalis lacking IreP exhibit remarkable hyperresistance to cephalosporins but not to antibiotics targeting other cellular processes. Further genetic analyses indicate that hyperresistance of the IreP mutant is mediated by the IreK kinase. Additionally, competition experiments reveal that hyperresistant DeltaireP mutants exhibit a substantial fitness defect in the absence of antibiotics, providing an evolutionary rationale for the use of a complex signaling system to control intrinsic cephalosporin resistance. These results support a model in which IreK and IreP act antagonistically via protein phosphorylation and dephosphorylation as part of a signal transduction circuit to regulate cellular adaptation to cephalosporin induced stress. IMPORTANCE: As a major cause of hospital-acquired infections, antibiotic-resistant enterococci represent a serious public health problem. Enterococci are well-known to exhibit intrinsic resistance to broad-spectrum cephalosporin antibiotics, a trait that enables them to proliferate in patients undergoing cephalosporin therapy, thereby predisposing these patients to acquisition of an enterococcal infection. Thus, inhibition of enterococcal cephalosporin resistance could represent an effective new strategy to prevent the emergence of hospital-acquired enterococcal infections. At this time, however, the molecular basis for cephalosporin resistance in E. faecalis is poorly understood. Our results begin to unravel the details of a new phosphorylation dependent signal transduction system that controls cephalosporin resistance in enterococci. Deeper understanding of the mechanism underlying cephalosporin resistance in E. faecalis may enable the development of new therapeutics designed to reduce the incidence of hospital-acquired enterococcal infections. PMID- 22045989 TI - Molecular dissection of an outbreak of carbapenem-resistant enterobacteriaceae reveals Intergenus KPC carbapenemase transmission through a promiscuous plasmid. AB - Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as major causes of health care-associated infections worldwide. This diverse collection of organisms with various resistance mechanisms is associated with increased lengths of hospitalization, costs of care, morbidity, and mortality. The global spread of CRE has largely been attributed to dissemination of a dominant strain of Klebsiella pneumoniae producing a serine beta-lactamase, termed K. pneumoniae carbapenemase (KPC). Here we report an outbreak of KPC-producing CRE infections in which the degree of horizontal transmission between strains and species of a promiscuous plasmid is unprecedented. Sixteen isolates, comprising 11 unique strains, 6 species, and 4 genera of bacteria, were obtained from 14 patients over the first 8 months of the outbreak. Of the 11 unique strains, 9 harbored the same highly promiscuous plasmid carrying the KPC gene bla(KPC). The remaining strains harbored distinct bla(KPC) plasmids, one of which was carried in a strain of Klebsiella oxytoca coisolated from the index patient and the other generated from transposition of the bla(KPC) element Tn4401. All isolates could be genetically traced to the index patient. Molecular epidemiological investigation of the outbreak was aided by the adaptation of nested arbitrary PCR (ARB-PCR) for rapid plasmid identification. This detailed molecular genetic analysis, combined with traditional epidemiological investigation, provides insights into the highly fluid dynamics of drug resistance transmission during the outbreak. IMPORTANCE The ease of horizontal transmission of carbapenemase resistance plasmids across strains, species, and genera of bacteria observed in this study has several important public health and epidemiological implications. First, it has the potential to promote dissemination of carbapenem resistance to new populations of Enterobacteriaceae, including organisms of low virulence, leading to the establishment of reservoirs of carbapenem resistance genes in patients and/or the environment and of high virulence, raising the specter of untreatable community associated infections. Second, recognition of plasmid-mediated outbreaks, such as those described here, is problematic because analysis of resistance plasmids from clinical isolates is laborious and technically challenging. Adaptation of nested arbitrary PCR (ARB-PCR) to investigate the plasmid outbreak facilitated our investigation, and the method may be broadly applicable to other outbreaks due to other conserved mobile genetic elements. Whether infection control measures that focus on preventing transmission of drug-resistant clones are effective in controlling dissemination of these elements is unknown. PMID- 22045990 TI - Reply to "South Asia instead of Nepal may be the origin of the Haitian cholera outbreak strain". PMID- 22045991 TI - Boxing, mixed martial arts, and other risky sports: is the BMA confused? PMID- 22045992 TI - How to spot a "spamnal". PMID- 22045993 TI - Governments pledge to clamp down on counterfeit drugs. PMID- 22045994 TI - Personal health budgets lack transparency, health department finds. PMID- 22045995 TI - Plans for public health in England are confused, warn MPs. PMID- 22045996 TI - Phylogenetic analysis of the teneurins: conserved features and premetazoan ancestry. AB - Teneurins are type II transmembrane proteins expressed during pattern formation and neurogenesis with an intracellular domain that can be transported to the nucleus and an extracellular domain that can be shed into the extracellular milieu. In Drosophila melanogaster, Caenorhabditis elegans, and mouse the knockdown or knockout of teneurin expression can lead to abnormal patterning, defasciculation, and abnormal pathfinding of neurites, and the disruption of basement membranes. Here, we have identified and analyzed teneurins from a broad range of metazoan genomes for nuclear localization sequences, protein interaction domains, and furin cleavage sites and have cloned and sequenced the intracellular domains of human and avian teneurins to analyze alternative splicing. The basic organization of teneurins is highly conserved in Bilateria: all teneurins have epidermal growth factor (EGF) repeats, a cysteine-rich domain, and a large region identical in organization to the carboxy-half of prokaryotic YD-repeat proteins. Teneurins were not found in the genomes of sponges, cnidarians, or placozoa, but the choanoflagellate Monosiga brevicollis has a gene encoding a predicted teneurin with a transmembrane domain, EGF repeats, a cysteine-rich domain, and a region homologous to YD-repeat proteins. Further examination revealed that most of the extracellular domain of the M. brevicollis teneurin is encoded on a single huge 6,829-bp exon and that the cysteine-rich domain is similar to sequences found in an enzyme expressed by the diatom Phaeodactylum tricornutum. This leads us to suggest that teneurins are complex hybrid fusion proteins that evolved in a choanoflagellate via horizontal gene transfer from both a prokaryotic gene and a diatom or algal gene, perhaps to improve the capacity of the choanoflagellate to bind to its prokaryotic prey. As choanoflagellates are considered to be the closest living relatives of animals, the expression of a primitive teneurin by an ancestral choanoflagellate may have facilitated the evolution of multicellularity and complex histogenesis in metazoa. PMID- 22045997 TI - Role of low-complexity sequences in the formation of novel protein coding sequences. AB - Low-complexity sequences are extremely abundant in eukaryotic proteins for reasons that remain unclear. One hypothesis is that they contribute to the formation of novel coding sequences, facilitating the generation of novel protein functions. Here, we test this hypothesis by examining the content of low complexity sequences in proteins of different age. We show that recently emerged proteins contain more low-complexity sequences than older proteins and that these sequences often form functional domains. These data are consistent with the idea that low-complexity sequences may play a key role in the emergence of novel genes. PMID- 22045998 TI - Inconsistencies in estimating the age of HIV-1 subtypes due to heterotachy. AB - Rate heterogeneity among lineages is a common feature of molecular evolution, and it has long impeded our ability to accurately estimate the age of evolutionary divergence events. The development of relaxed molecular clocks, which model variable substitution rates among lineages, was intended to rectify this problem. Major subtypes of pandemic HIV-1 group M are thought to exemplify closely related lineages with different substitution rates. Here, we report that inferring the time of most recent common ancestor of all these subtypes in a single phylogeny under a single (relaxed) molecular clock produces significantly different dates for many of the subtypes than does analysis of each subtype on its own. We explore various methods to ameliorate this problem. We conclude that current molecular dating methods are inadequate for dealing with this type of substitution rate variation in HIV-1. Through simulation, we show that heterotachy causes root ages to be overestimated. PMID- 22045999 TI - A living fossil in the genome of a living fossil: Harbinger transposons in the coelacanth genome. AB - Emerging data from the coelacanth genome are beginning to shed light on the origin and evolution of tetrapod genes and noncoding elements. Of particular relevance is the realization that coelacanth retains active copies of transposable elements that once served as raw material for the evolution of new functional sequences in the vertebrate lineage. Recognizing the evolutionary significance of coelacanth genome in this regard, we employed an ab initio search strategy to further classify its repetitive complement. This analysis uncovered a class of interspersed elements (Latimeria Harbinger 1-LatiHarb1) that is a major contributor to coelacanth genome structure and gene content (~1% to 4% or the genome). Sequence analyses indicate that 1) each ~8.7 kb LatiHarb1 element contains two coding regions, a transposase gene and a gene whose function is as yet unknown (MYB-like) and 2) copies of LatiHarb1 retain biological activity in the coelacanth genome. Functional analyses verify transcriptional and enhancer activities of LatiHarb1 in vivo and reveal transcriptional decoupling that could permit MYB-like genes to play functional roles not directly linked to transposition. Thus, LatiHarb1 represents the first known instance of a harbinger superfamily transposon with contemporary activity in a vertebrate genome. Analyses of LatiHarb1 further corroborate the notion that exaptation of anciently active harbinger elements gave rise to at least two vertebrate genes (harbi1 and naif1) and indicate that the vertebrate gene tsnare1 also traces its ancestry to this transposon superfamily. Based on our analyses of LatiHarb1, we speculate that several functional features of harbinger elements may predispose the transposon superfamily toward recurrent exaptive evolution of cellular coding genes. In addition, these analyses further reinforce the broad utility of the coelacanth genome and other "outgroup" genomes in understanding the ancestry and evolution of vertebrate genes and genomes. PMID- 22046000 TI - Emergent complexity in Myosin V-based organelle inheritance. AB - How is adaptability generated in a system composed of interacting cellular machineries, each with a separate and functionally critical job to perform? The machinery for organelle inheritance is precisely one such system, requiring coordination between robust and ancient cellular modules, including the cell cycle, cytoskeleton, and organelle biogenesis/identity. Budding yeasts have emerged as powerful models to study these processes, which are critical for cellular survival, propagation, and differentiation, as organelles must compete for access to myosin V motors that travel along polarized actin cables to vectorially deliver bound cargo to the bud. Under the direction of the cell cycle, myosin V motors are recruited to organelles by specific interactions between their carboxyl-terminal globular tail domains and organelle-specific receptors. We used comparative genomics, phylogenetics, and secondary structure modeling to characterize the evolutionary history of these organelle-specific receptors. We find that while some receptors are retained widely across the animals and fungi, others are limited primarily to the Saccharomycetaceae family of budding yeast, with the emergent pattern of a conserved biogenic and inheritance factor often paired with an evolutionarily novel inheritance adaptor. We propose an evolutionary model whereby the emergence of myosin V-based organelle inheritance has utilized mechanisms of paralogy, mutation, and the appearance of pliable evolutionarily novel adaptor proteins. Our findings suggest an overarching evolutionary mechanism for how diverse cargoes compete for a single myosin V motor in organelle transport and detail one system's solution to obtaining evolutionary adaptability amongst constrained cellular modules. PMID- 22046001 TI - Late-replicating domains have higher divergence and diversity in Drosophila melanogaster. AB - Several reports from mammals indicate that an increase in the mutation rate in late-replicating regions may, in part, be responsible for the observed genomic heterogeneity in neutral substitution rates and levels of diversity, although the mechanisms for this remain poorly understood. Recent evidence also suggests that late replication is associated with high mutability in yeast. This then raises the question as to whether a similar effect is operating across all eukaryotes. Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence. Given the availability of genome-wide replication timing profiles for D. melanogaster, we now return to this issue. Consistent with what is seen in other taxa, we find that divergence at synonymous sites in exon cores, as well as divergence at putatively unconstrained intronic sites, is elevated in late-replicating regions. Analysis of genes with low codon usage bias suggests a ~30% difference in mutation rate between the earliest and the latest replicating sequence. Intronic sequence suggests a more modest difference. We additionally show that an increase in diversity in late replicating sequences is not owing to replication timing covarying with the local recombination rate. If anything, the effects of recombination mask the impact of replication timing. We conclude that, contrary to prior reports and consistent with what is seen in mammals and yeast, there is indeed a relationship between rates of nucleotide divergence and diversity and replication timing that is consistent with an increase in the mutation rate during late S-phase in D. melanogaster. It is therefore plausible that such an effect might be common among eukaryotes. The result may have implications for the inference of positive selection. PMID- 22046002 TI - Radiation and functional diversification of alpha keratins during early vertebrate evolution. AB - The conquest of land was arguably one of the most fundamental ecological transitions in vertebrates and entailed significant changes in skin structure and appendages to cope with the new environment. In extant tetrapods, the rigidity of the integument is largely created by type I and type II keratins, which are structural proteins essential in forming a strong cytoplasmic network. It is expected that such proteins have undergone fundamental changes in both stem and crown tetrapods. Here, we integrate genomic, phylogenetic, and expression data in a comprehensive study on the early evolution and functional diversification of tetrapod keratins. Our analyses reveal that all type I and type II tetrapod keratins evolved from only two genes that were present in the ancestor of extant vertebrates. Subsequently, the water-to-land transition in the stem lineage of tetrapods was associated with a major radiation and functional diversification of keratin genes. These duplications acquired functions that serve rigidity in integumental hard structures and were the prime for subsequent independent keratin diversification in tetrapod lineages. PMID- 22046003 TI - The biology of aging: 1985-2010 and beyond. AB - In this contribution to the series of reflective essays celebrating the 25th anniversary of The FASEB Journal, our task is to assess the growth of research on the biology of aging during this period and to suggest where we might be heading during the next 25 yr. A review of the literature suggests a healthy acceleration of progress during the past decade, perhaps largely due to progress on the genetics of longevity of model organisms. Progress on the genetics of health span in these model organisms has lagged, however. Research on the genetic basis of the remarkable interspecific variations in life span has only recently begun to be seriously addressed. The spectacular advances in genomics should greatly accelerate progress. Research on environmental effects on life span and health span needs to be accelerated. Stochastic variations in gene expression in aging have only recently been addressed. These can lead to random departures from homeostasis during aging.-Martin, G. M. The biology of aging: 1985-2010 and beyond. PMID- 22046004 TI - Molecular determinants of pentamidine-induced hERG trafficking inhibition. AB - Pentamidine is an antiprotozoal compound that clinically causes acquired long QT syndrome (acLQTS), which is associated with prolonged QT intervals, tachycardias, and sudden cardiac arrest. Pentamidine delays terminal repolarization in human heart by acutely blocking cardiac inward rectifier currents. At the same time, pentamidine reduces surface expression of the cardiac potassium channel I(Kr)/human ether a-go-go-related gene (hERG). This is unusual in that acLQTS is caused most often by direct block of the cardiac potassium current I(Kr)/hERG. The present study was designed to provide a more complete picture of how hERG surface expression is disrupted by pentamidine at the cellular and molecular levels. Using biochemical and electrophysiological methods, we found that pentamidine exclusively inhibits hERG export from the endoplasmic reticulum to the cell surface in a heterologous expression system as well as in cardiomyocytes. hERG trafficking inhibition could be rescued in the presence of the pharmacological chaperone astemizole. We used rescue experiments in combination with an extensive mutational analysis to locate an interaction site for pentamidine at phenylalanine 656, a crucial residue in the canonical drug binding site of terminally folded hERG. Our data suggest that pentamidine binding to a folding intermediate of hERG arrests channel maturation in a conformational state that cannot be exported from the endoplasmic reticulum. We propose that pentamidine is the founding member of a novel pharmacological entity whose members act as small molecule antichaperones. PMID- 22046005 TI - Evidence for a common pharmacological interaction site on K(Ca)2 channels providing both selective activation and selective inhibition of the human K(Ca)2.1 subtype. AB - We have previously identified Ser293 in transmembrane segment 5 as a determinant for selective K(Ca)2.1 channel activation by GW542573X (4-(2 methoxyphenylcarbamoyloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester). Now we show that Ser293 mediates both activation and inhibition of K(Ca)2.1: CM TPMF (N-{7-[1-(4-chloro-2-methylphenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-2 yl}-N'-methoxy-formamidine) and B-TPMF (N-{7-[1-(4-tert-butyl-phenoxy)ethyl] [1,2,4]triazolo[1,5-a]pyrimidin-2-yl}-N'-methoxy-formamidine), two newly identified and structurally related [1,2,4]triazolo[1,5-a]pyrimidines, act either as activators or as inhibitors of the human K(Ca)2.1 channel. Whereas (-)-CM-TPMF activates K(Ca)2.1 with an EC(50) value of 24 nM, (-)-B-TPMF inhibits the channel with an IC(50) value of 31 nM. In contrast, their (+)-enantiomers are 40 to 100 times less active. Both (-)-CM-TPMF and (-)-B-TPMF are subtype-selective, with 10 to 20-fold discrimination toward other K(Ca)2 channels and the K(Ca)3 channel. Coapplication experiments reveal competitive-like functional interactions between the effects of (-)-CM-TPMF and (-)-B-TPMF. Despite belonging to a different chemical class than GW542573X, the K(Ca)2.1 selectivity of (-)-CM-TPMF and (-)-B TPMF depend critically on Ser293 as revealed by loss- and gain-of-function mutations. We conclude that compounds occupying the TPMF site may either positively or negatively influence the gating process depending on their substitution patterns. It is noteworthy that (-)-CM-TPMF is 10 times more potent on K(Ca)2.1 than NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime), an unselective but hitherto the most potent K(Ca)3/K(Ca)2 channel activator. (-)-B-TPMF is the first small-molecule inhibitor with significant selectivity among the K(Ca)2 channel subtypes. In contrast to peptide blockers such as apamin and scyllatoxin, which preferentially affect K(Ca)2.2, (-)-B-TPMF exhibits K(Ca)2.1 selectivity. These high-affinity compounds, which exert opposite effects on K(Ca)2.1 gating, may help define physiological or pathophysiological roles of this channel. PMID- 22046006 TI - Time for patient leaflets on the Hajj. PMID- 22046007 TI - Broad consent is informed consent. PMID- 22046009 TI - Secret filming of GPs was unethical and unwise. PMID- 22046010 TI - Secret filming did not prove the point. PMID- 22046011 TI - Treatment of rheumatoid arthritis is good medicine. PMID- 22046012 TI - The dark side of the sun. PMID- 22046013 TI - Spare me the English middle class's snobbery about trade. PMID- 22046014 TI - Don't forget other medical suppliers. PMID- 22046015 TI - Disinvesting from prostate cancer screening. PMID- 22046016 TI - Relatives should not be able to countermand a dead person's wishes. PMID- 22046017 TI - Residential home assessments are tip of 36 year iceberg. PMID- 22046018 TI - Current treatment of rheumatoid arthritis. PMID- 22046020 TI - Make countries' health spending easier to compare, says OECD. PMID- 22046021 TI - Drug firms have to pay $162m in damages over hepatitis C infection. PMID- 22046023 TI - Achieving the goals of effective, safe, and individualized cancer care. PMID- 22046024 TI - Adaptive clinical trial designs for simultaneous testing of matched diagnostics and therapeutics. AB - A critical challenge in the development of new molecularly targeted anticancer drugs is the identification of predictive biomarkers and the concurrent development of diagnostics for these biomarkers. Developing matched diagnostics and therapeutics will require new clinical trial designs and methods of data analysis. The use of adaptive design in phase III trials may offer new opportunities for matched diagnosis and treatment because the size of the trial can allow for subpopulation analysis. We present an adaptive phase III trial design that can identify a suitable target population during the early course of the trial, enabling the efficacy of an experimental therapeutic to be evaluated within the target population as a later part of the same trial. The use of such an adaptive approach to clinical trial design has the potential to greatly improve the field of oncology and facilitate the development of personalized medicine. PMID- 22046025 TI - Identification and elucidation of the biology of adverse events: the challenges of safety assessment and translational medicine. AB - There has been an explosion of technology-enabled scientific insight into the basic biology of the causes of adverse events. This has been driven, in part, by the development of the various "omics" tools (e.g., genomics, proteomics, and metabolomics) and associated bioinformatics platforms. Meanwhile, for decades, changes in preclinical testing protocols and guidelines have been limited. Preclinical safety testing currently relies heavily on the use of outdated animal models. Application of systems biology methods to evaluation of toxicities in oncology treatments can accelerate the introduction of safe, effective drugs. Systems biology adds insights regarding the causes and mechanisms of adverse effects, provides important and actionable information to help understand the risks and benefits to humans, focuses testing on methods that add value to the safety testing process, and leads to modifications of chemical entities to reduce liabilities during development. Leveraging emerging technologies, such as genomics and proteomics, may make preclinical safety testing more efficient and accurate and lead to better safety decisions. The development of a U.S. Food and Drug Administration guidance document on the use of systems biology in clinical testing would greatly benefit the development of drugs for oncology by communicating the potential application of specific methodologies, providing a framework for qualification and application of systems biology outcomes, and providing insight into the challenges and limitations of systems biology in the regulatory decision-making process. PMID- 22046026 TI - Integrating pain metrics into oncology clinical trials. AB - Cancer-related pain is highly prevalent and often severe, and as a result is often one of the defining experiences for patients with malignancy. Patients and patients' families almost always live with the ever-present reality that cancer treatment and progression may be accompanied by pain. For patients nearing the end of life, most fear that their final days will be spent living with the terrible effects of the disease, the most important of which is pain. Despite this, there is far less systematic research on the mechanisms of cancer-related pain or on the development of new agents to reduce or eliminate pain in cancer patients compared with research to combat the disease itself. Further, even when the focus of research is treatment of the tumor, the effects of anticancer treatments on pain are often underreported in publications and other forums. To illustrate the relative drought in the cancer pain control area, there have been no new drugs approved for cancer-related pain in recent years. A number of methodologic and logistical challenges that hinder the ability to assess pain response in clinical trials are discussed in this article. Possible ways to address these challenges are also discussed. PMID- 22046027 TI - Using patient-initiated study participation in the development of evidence for personalized cancer therapy. AB - Personalized cancer therapy offers the promise of delivering the right treatments to the right patients to improve patient outcomes and quality of life, while reducing exposure to ineffective therapies and the cost of cancer care. Realizing this promise depends in large part on our ability to generate timely and sufficiently detailed information regarding factors that influence treatment response. Generating this evidence through the traditional physician investigator initiated clinical trial system has proved to be challenging, given poor recruitment rates and low compliance with requests for biospecimen collection. As a result, our current understanding of treatment response is inadequate, particularly for cancer therapies that have been in use for many years. Patient initiated study participation may offer a new model for evidence generation that capitalizes on strong patient interest in furthering research to inform better and more tailored cancer therapies. In this approach, patients are engaged and recruited directly by the sponsor of an Institutional Review Board-approved study, and patients subsequently drive the participation of their health care providers to facilitate collection of required data and tissue samples. The ultimate goal of these studies is to generate evidence of sufficient quality to inform regulatory decisions (i.e., labeling changes for marketed therapies to reflect populations most likely to respond) and treatment selection. Here, we describe a hypothetical prospective observational study in non-small cell lung cancer that could serve as a model for patient-initiated study participation applied to understand molecular determinants of treatment response. Key elements discussed include study design, patient engagement, and data/biospecimen collection and management principles. PMID- 22046029 TI - Excessive activity of cathepsin K is associated with cartilage defects in a zebrafish model of mucolipidosis II. AB - The severe pediatric disorder mucolipidosis II (ML-II; also known as I-cell disease) is caused by defects in mannose 6-phosphate (Man-6-P) biosynthesis. Patients with ML-II exhibit multiple developmental defects, including skeletal, craniofacial and joint abnormalities. To date, the molecular mechanisms that underlie these clinical manifestations are poorly understood. Taking advantage of a zebrafish model of ML-II, we previously showed that the cartilage morphogenesis defects in this model are associated with altered chondrocyte differentiation and excessive deposition of type II collagen, indicating that aspects of development that rely on proper extracellular matrix homeostasis are sensitive to decreases in Man-6-P biosynthesis. To further investigate the molecular bases for the cartilage phenotypes, we analyzed the transcript abundance of several genes in chondrocyte-enriched cell populations isolated from wild-type and ML-II zebrafish embryos. Increased levels of cathepsin and matrix metalloproteinase (MMP) transcripts were noted in ML-II cell populations. This increase in transcript abundance corresponded with elevated and sustained activity of several cathepsins (K, L and S) and MMP-13 during early development. Unlike MMP-13, for which higher levels of protein were detected, the sustained activity of cathepsin K at later stages seemed to result from its abnormal processing and activation. Inhibition of cathepsin K activity by pharmacological or genetic means not only reduced the activity of this enzyme but led to a broad reduction in additional protease activity, significant correction of the cartilage morphogenesis phenotype and reduced type II collagen staining in ML-II embryos. Our findings suggest a central role for excessive cathepsin K activity in the developmental aspects of ML-II cartilage pathogenesis and highlight the utility of the zebrafish system to address the biochemical underpinnings of metabolic disease. PMID- 22046030 TI - Mutation of zebrafish dihydrolipoamide branched-chain transacylase E2 results in motor dysfunction and models maple syrup urine disease. AB - Analysis of zebrafish mutants that demonstrate abnormal locomotive behavior can elucidate the molecular requirements for neural network function and provide new models of human disease. Here, we show that zebrafish quetschkommode (que) mutant larvae exhibit a progressive locomotor defect that culminates in unusual nose-to tail compressions and an inability to swim. Correspondingly, extracellular peripheral nerve recordings show that que mutants demonstrate abnormal locomotor output to the axial muscles used for swimming. Using positional cloning and candidate gene analysis, we reveal that a point mutation disrupts the gene encoding dihydrolipoamide branched-chain transacylase E2 (Dbt), a component of a mitochondrial enzyme complex, to generate the que phenotype. In humans, mutation of the DBT gene causes maple syrup urine disease (MSUD), a disorder of branched chain amino acid metabolism that can result in mental retardation, severe dystonia, profound neurological damage and death. que mutants harbor abnormal amino acid levels, similar to MSUD patients and consistent with an error in branched-chain amino acid metabolism. que mutants also contain markedly reduced levels of the neurotransmitter glutamate within the brain and spinal cord, which probably contributes to their abnormal spinal cord locomotor output and aberrant motility behavior, a trait that probably represents severe dystonia in larval zebrafish. Taken together, these data illustrate how defects in branched-chain amino acid metabolism can disrupt nervous system development and/or function, and establish zebrafish que mutants as a model to better understand MSUD. PMID- 22046031 TI - Preparation of cuticles from feeding Drosophila larvae. AB - The Drosophila cuticle carries a rich array of morphological details. Thus, cuticle examination has had a central role in the history of genetics. Studies of the Drosophila cuticle have focused mainly on first-instar larvae and adult cuticular morphology. Although the cuticles of second- and third-instar larvae are strikingly different from those of the first instar, these differences have been poorly studied. This protocol describes three methods for preparing cuticles from fed larvae. One commonly used procedure involves manually pricking the larvae. A simpler method for preparing larval cuticles is to burst the larvae once they have been mounted. This method is used for first- and second-instar larvae and does not require pricking; it removes the gut contents by "popping" the rear of the embryo using pressure from the coverslip. If just the right amount of medium is used, the coverslip will be pulled toward the slide, applying pressure on the samples. The larvae usually burst from their posterior ends. Also presented is an alternative procedure designed specifically for the use with third-instar larvae, although the "pricking" method can be used at this stage. PMID- 22046028 TI - The postsynaptic organization of synapses. AB - The postsynaptic side of the synapse is specialized to receive the neurotransmitter signal released from the presynaptic terminal and transduce it into electrical and biochemical changes in the postsynaptic cell. The cardinal functional components of the postsynaptic specialization of excitatory and inhibitory synapses are the ionotropic receptors (ligand-gated channels) for glutamate and gamma-aminobutyric acid (GABA), respectively. These receptor channels are concentrated at the postsynaptic membrane and embedded in a dense and rich protein network comprised of anchoring and scaffolding molecules, signaling enzymes, cytoskeletal components, as well as other membrane proteins. Excitatory and inhibitory postsynaptic specializations are quite different in molecular organization. The postsynaptic density of excitatory synapses is especially complex and dynamic in composition and regulation; it contains hundreds of different proteins, many of which are required for cognitive function and implicated in psychiatric illness. PMID- 22046032 TI - Preparation of Drosophila eye specimens for scanning electron microscopy. AB - Scanning electron microscopy (SEM) allows for high-magnification analysis of the external structures of the Drosophila eye. In this article, three methods are provided: one for eyes that are to be critical-point-dried (CPD) and two alternatives if a critical point drier is not available. The major difference between the first method and the other two is a preliminary fixation step. Drosophila eyes have a tendency to collapse when CPD, so fixing the animals before critical point drying improves the yield of good specimens. PMID- 22046033 TI - Preparation of Drosophila eye specimens for transmission electron microscopy. AB - Transmission electron microscopy (TEM) allows for high-magnification ultrastructural analysis of the Drosophila eye. The fixation protocol described here works well for Drosophila eye tissue, including larval imaginal discs and pupal and adult retinas. PMID- 22046034 TI - Conditioning to colors: a population assay for visual learning in Drosophila. AB - Vision is a major sensory modality in Drosophila behavior, with more than one half of the Drosophila brain devoted to visual processing. The mechanisms of vision in Drosophila can be studied in individuals and in populations of flies by using various paradigms. Although there has never been a widely used population assay for visual learning in Drosophila, some population paradigms have shown significant visual learning. These studies use colors as conditioned stimuli (CS) and shaking as the unconditioned stimulus (US). A simple version of the paradigm, conditioning to colors using a shaking device, is described here. A conditioning chamber, called a crab, is designed to center the flies after shaking by having them tumble down to the lowest point between joined glass tubes forming a V. Thus, vibration should be just strong enough to center most flies. After shaking, flies display a geotactic response and climb up either side of the V, and their choice of which side to climb is influenced by color displays on either side. The proportion of flies on either side determines the flies' natural preference or their learned avoidance of a color associated with shaking. PMID- 22046035 TI - The optomotor maze: a population assay for visual perception in Drosophila. AB - Vision is a major sensory modality in Drosophila behavior, with more than one half of the Drosophila brain devoted to visual processing. The mechanisms of vision in Drosophila can now be studied in individuals and in populations of flies by using various paradigms. The optomotor maze, described here, is a novel and efficient approach for querying visual perception in Drosophila populations. The optomotor maze setup is very simple: An eight-choice maze consisting of 3-mm paths grooved into a transparent Plexiglas or acrylic slab is placed over an upturned cathode ray tube (CRT) monitor on which visuals are displayed. The placement or movement of the visuals on the CRT, which the flies can see through the flat bottom of the maze, influences their turning behavior at each choice point. This paradigm can be adapted for visual learning by simply rerunning flies in the maze (habituation) or as a more sophisticated version of the aversive phototaxic suppression (APS) paradigm. PMID- 22046036 TI - Imaging of membrane systems and membrane traffic in living cells. AB - Eukaryotic cells are composed of an intricate system of internal membranes that are organized into different compartments--including the endoplasmic reticulum (ER), the nuclear envelope, the Golgi complex (GC), lysosomes, endosomes, caveolae, mitochondria, and peroxisomes--that perform specialized tasks within the cell. The localization and dynamics of intracellular compartments are now being studied in living cells because of the availability of green fluorescent protein (GFP)-fusion proteins and recent advances in fluorescent microscope imaging systems. Results using these techniques are revealing how intracellular compartments maintain their steady-state organization and distributions, how they undergo growth and division, and how they transfer protein and lipid components between themselves through the formation and trafficking of membrane transport intermediates. This article describes methods using GFP-fusion proteins to visualize the behavior of organelles and to track membrane-bound transport intermediates moving between them. Practical issues related to the construction and expression of GFP-fusion proteins are discussed first. These are essential for optimizing the brightness and expression levels of GFP-fusion proteins so that intracellular membrane-bound structures containing these fusion proteins can be readily visualized. Next, techniques for performing time-lapse imaging using a confocal laser-scanning microscope (CLSM) are detailed, including the use of photobleaching to highlight organelles and transport intermediates. Methods for the acquisition and analysis of data are then discussed. Finally, commonly used and exciting new approaches for perturbing membrane traffic are outlined. PMID- 22046037 TI - Time-lapse imaging of membrane traffic in living cells. AB - Eukaryotic cells are composed of an intricate system of internal membranes that are organized into different compartments--including the endoplasmic reticulum (ER), the nuclear envelope, the Golgi complex (GC), lysosomes, endosomes, caveolae, mitochondria, and peroxisomes--that perform specialized tasks within the cell. The localization and dynamics of intracellular compartments are now being studied in living cells because of the availability of green fluorescent protein (GFP)-fusion proteins and recent advances in fluorescent microscope imaging systems. This protocol describes the use of the confocal laser-scanning microscope (CLSM) for time-lapse imaging of one or more fluorescent markers. PMID- 22046038 TI - Photobleaching regions of living cells to monitor membrane traffic. AB - Eukaryotic cells are composed of an intricate system of internal membranes that are organized into different compartments--including the endoplasmic reticulum (ER), the nuclear envelope, the Golgi complex (GC), lysosomes, endosomes, caveolae, mitochondria, and peroxisomes--that perform specialized tasks within the cell. The localization and dynamics of intracellular compartments are now being studied in living cells because of the availability of green fluorescent protein (GFP)-fusion proteins and recent advances in fluorescent microscope imaging systems. This protocol outlines two methods for photobleaching living cells to monitor membrane traffic. The first method involves selective photobleaching using a confocal laser-scanning microscope (CLSM) that can bleach discrete selected regions of interest. As outlined in the second method, photobleaching can also be performed with older CLSMs that lack the capacity for selective photobleaching. In this case, photobleaching is accomplished by zooming into a small region of the cell and scanning with full laser power. PMID- 22046039 TI - Activating photoactivatable proteins with laser light to visualize membrane systems and membrane traffic in living cells. AB - Eukaryotic cells are composed of an intricate system of internal membranes that are organized into different compartments--including the endoplasmic reticulum (ER), the nuclear envelope, the Golgi complex (GC), lysosomes, endosomes, caveolae, mitochondria, and peroxisomes--that perform specialized tasks within the cell. The localization and dynamics of intracellular compartments are now being studied in living cells because of the availability of green fluorescent protein (GFP)-fusion proteins and recent advances in fluorescent microscope imaging systems, such as the confocal laser-scanning microscope (CLSM). This protocol describes the steps for activating one of the first photoactivatable proteins, PA-GFP. PMID- 22046040 TI - Comparative genomic hybridization to detect variation in the copy number of large DNA segments. AB - Array comparative genomic hybridization (CGH) is an excellent tool to scan the genome for copy number variations (CNVs) when used conscientiously. This article is intended to provide an understanding of the basic principles of array CGH and the different options available to the user to design their array CGH experiments. Specifically, the six subsections discuss the different array platforms available, test and reference DNA preparation, reference DNA choice, the basics of hybridization, data processing, and our current understanding of CNVs in the human genome. PMID- 22046041 TI - Measuring neuronal population activity using 3D laser scanning. AB - Neural tissue is organized in three-dimensional (3D) networks of neuronal and glial cell populations. To understand the functional organization of these networks, it is desirable to achieve 3D activity measurements from large cell populations in intact tissue with high temporal resolution. Repeated acquisition of image stacks with standard laser-scanning microscopes is too slow. This protocol describes fast 3D calcium imaging in the living brain using mechanical laser scanning with standard galvanometric mirrors and a piezoelectric focusing element. The purpose of 3D laser scanning is to create a 3D line scan that samples relatively homogenously from a particular observation volume. The spatial resolution of this approach is low, except along the line. However, the main goal is not to resolve subcellular structures, but rather to hit as many cell bodies as possible within the volume. In this manner, local network activity can be inferred from the somatic calcium signals of a significant fraction of the cell population. With a sinusoidal swinging microscope objective as a constraint, 3D scan trajectories are generated that sample fluorescence signals from the majority of cells within a cuboidal volume. Measurements with 10-Hz temporal resolution can be achieved for population calcium signals from several hundreds of identified neurons and glial cells within cuboids with side lengths of ~250 um. An example cellular 3D orientation map of the rat visual cortex is presented. This 3D laser-scanning technique enables direct observation of in vivo neural network dynamics in cell populations of substantial size. PMID- 22046042 TI - Time-lapse imaging of fluorescently labeled live cells in the embryonic mammalian forebrain. AB - Time-lapse imaging of fluorescently labeled cells in organotypic slice culture provides a unique window through which to view development of the embryonic forebrain. The live imaging approach allows investigators to directly observe and record neurogenic and gliogenic divisions in the developing forebrain, to record the proliferative behavior of embryonic precursor cells, and to track newborn cells as they migrate from the proliferative zones to their final destination. This approach allows for identification and characterization of embryonic precursor cells, permits the physiological and immunohistochemical characterization of the fluorescent cells under study, and presents an opportunity to test hypotheses about mechanisms that guide developmental processes in the forebrain. This article describes a protocol for time-lapse imaging of fluorescently labeled cells in the embryonic forebrain of organotypic slice cultures. The procedure does not require prohibitively expensive on-stage incubation systems, and can yield reliable data from embryonic slices for up to 1 wk. Tracking the movement of labeled cells in slice culture is relatively straightforward in those cases in which there are few labeled cells. Although this approach is time intensive, it provides beautifully detailed images that reveal morphological and functional data from labeled cells over time, and can yield a significant amount of data from each cell. PMID- 22046043 TI - 4D fluorescent imaging of embryonic quail development. AB - Traditionally, our understanding of developmental biology has been based on the fixation and study of embryonic samples. Detailed microscopic scrutiny of static specimens at varying ages allowed for anatomical assessment of tissue development. The advent of confocal and two-photon excitation (2PE) microscopy enables researchers to acquire volumetric images in three dimensions (x, y, and z) plus time (t). Here, we present techniques for acquisition and analysis of three-dimensional (3D) time-lapse data. Both confocal microscopy and 2PE microscopy techniques are used. Data processing for tiled image stitching and time-lapse analysis is also discussed. The development of a transgenic Japanese quail system, as discussed here, has provided an embryonic model that is more easily accessible than mammalian models and more efficient to breed than the classic avian model, the chicken. PMID- 22046044 TI - Preparation and 4D fluorescent imaging of quail embryos. AB - Traditionally, our understanding of developmental biology has been based on the fixation and study of embryonic samples. Detailed microscopic scrutiny of static specimens at varying ages allowed for anatomical assessment of tissue development. The advent of confocal and two-photon excitation (2PE) microscopy enables researchers to acquire volumetric images in three dimensions (x, y, and z) plus time (t). The development of transgenic Japanese quail has provided an embryonic model system that is more easily accessible than mammalian models and more efficient to breed than the classic avian model, the chicken. This protocol describes the methods necessary to prepare transgenic quail embryos for imaging in vitro, and for acquiring, processing, and analyzing three-dimensional (3D) time-lapse images. PMID- 22046045 TI - Cyclodextrin-containing polycations for nucleic acid delivery. AB - Numerous nonviral systems have been developed for the delivery of nucleic acids to cultured cells and to particular cell types in vivo. These systems vary with regard to their toxicity, immunogenicity, and ability to target particular cell surface receptors and/or cell types. A class of linear cationic polymers containing the sugar beta-cyclodextrin has been shown to be effective at delivering a variety of nucleic acids in vivo, including plasmid DNA, DNAzymes, and short interfering RNAs (siRNAs). These polymer-nucleic acid complexes (polyplexes) can be further modified to incorporate a targeting ligand such as transferrin to induce preferential uptake of polyplexes by cells expressing high levels of the cognate receptor. This article presents background information on cyclodextrin-containing polycations. PMID- 22046046 TI - In vitro transfection using cyclodextrin-containing polycations. AB - Numerous nonviral systems have been developed for the delivery of nucleic acids to cultured cells and to particular cell types in vivo. These systems vary with regard to their toxicity, immunogenicity, and ability to target particular cell surface receptors and/or cell types. A class of linear cationic polymers containing the sugar beta-cyclodextrin has been shown to be effective at delivering a variety of nucleic acids in vivo, including plasmid DNA, DNAzymes, and short interfering RNAs (siRNAs). This protocol describes a procedure for the use of cyclodextrin-containing polycations in vitro. For in vitro transfection, salt stabilization and cell targeting are unnecessary, so polyplexes consist of cyclodextrin-containing polycations and nucleic acids only. PMID- 22046047 TI - In vivo transfection using cyclodextrin-containing polycations. AB - Numerous nonviral systems have been developed for the delivery of nucleic acids to cultured cells and to particular cell types in vivo. These systems vary with regard to their toxicity, immunogenicity, and ability to target particular cell surface receptors and/or cell types. A class of linear cationic polymers containing the sugar beta-cyclodextrin (beta-CD) has been shown to be effective at delivering a variety of nucleic acids in vivo, including plasmid DNA, DNAzymes, and short interfering RNAs (siRNAs). These polymer-nucleic acid complexes (polyplexes) can be further modified to incorporate a targeting ligand such as transferrin to induce preferential uptake of polyplexes by cells expressing high levels of the cognate receptor. This protocol describes a procedure for the use of cyclodextrin-containing polycations (CDPs) in vivo. Salt stabilization and cell targeting are critical to the success of in vivo transfection using CDPs, so adamantane-poly(ethylene glycol) (AD-PEG) conjugates (both unmodified AD-PEG and an AD-PEG-Ligand conjugate) are included in these formulations. The amount of the AD-PEG-Ligand conjugate included depends on numerous factors, including its effect on polyplex stability (influenced by ligand size and charge) and the density of the cognate receptor on target cell type(s). Some targeting ligands may have extreme sizes or net charges that could present a challenge to their incorporation into these polyplex formulations. PMID- 22046048 TI - Optical traps to study properties of molecular motors. AB - In vitro motility assays enabled the analysis of coupling between ATP hydrolysis and movement of myosin along actin filaments or kinesin along microtubules. Single-molecule assays using laser trapping have been used to obtain more detailed information about kinesins, myosins, and processive DNA enzymes. The combination of in vitro motility assays with laser-trap measurements has revealed detailed dynamic structural changes associated with the ATPase cycle. This article describes the use of optical traps to study processive and nonprocessive molecular motor proteins, focusing on the design of the instrument and the assays to characterize motility. PMID- 22046049 TI - Attachment of anti-GFP antibodies to microspheres for optical trapping experiments. AB - In vitro motility assays enabled the analysis of coupling between ATP hydrolysis and movement of myosin along actin filaments or kinesin along microtubules. Single-molecule assays using laser trapping have been used to obtain more detailed information about kinesins, myosins, and processive DNA enzymes. The combination of in vitro motility assays with laser-trap measurements has revealed detailed dynamic structural changes associated with the ATPase cycle. This protocol describes a method for attaching anti-GFP (green fluorescent protein) antibodies to microspheres. GFP-motor fusion proteins can then be adsorbed to the microspheres for use in single-molecule motility studies and optical trapping experiments. PMID- 22046051 TI - The physical therapist as a diagnostician: how do we, should we, and could we use information about pathology in our practice? PMID- 22046050 TI - The optical trapping dumbbell assay for nonprocessive motors or motors that turn around filaments. AB - In vitro motility assays enabled the analysis of coupling between ATP hydrolysis and movement of myosin along actin filaments or kinesin along microtubules. Single-molecule assays using laser trapping have been used to obtain more detailed information about kinesins, myosins, and processive DNA enzymes. The combination of in vitro motility assays with laser-trap measurements has revealed detailed dynamic structural changes associated with the ATPase cycle. This protocol describes the preparation of biotin-actin filaments and coverslips coated with polystyrene beads. These are then used in optical trapping dumbbell assays to study interactions between motors and filaments. PMID- 22046052 TI - Role of angiotensin in ovarian follicular development and ovulation in mammals: a review of recent advances. AB - Angiotensin (Ang) II is widely known for its role in the control of systemic blood vessels. Moreover, Ang II acts on the vascular control of ovarian function, corpus luteum formation, and luteolysis. Over the past 10 years, our research group has been studying the new concept of the renin-angiotensin system (RAS) as an autocrine/paracrine factor regulating steroidogenesis and promoting different cellular responses in the ovary, beyond vascular function. We have developed and used different in vivo and in vitro experimental models to study the role of RAS in the ovary and a brief overview of our findings is presented here. It is widely accepted that there are marked species differences in RAS function in follicle development. Examples of species-specific functions of the RAS in the ovary include the involvement of Ang II in the regulation of follicle atresia in rats vs the requirement of this peptide for the dominant follicle development and ovulation in rabbits and cattle. More recently, Ang-(1-7), its receptor, and enzymes for its synthesis (ACE2, NEP, and PEP) were identified in bovine follicles, implying that Ang-(1-7) has an ovarian function. Other novel RAS components (e.g. (pro)renin receptor and renin-binding protein) recently identified in the bovine ovary show that ovarian RAS is poorly understood and more complex than previously thought. In the present review, we have highlighted the progress toward understanding the paracrine and autocrine control of ovarian antral follicle development and ovulation by ovarian tissue RAS, focusing on in vivo studies using cattle as a model. PMID- 22046054 TI - Ceramide and mitochondrial function in aging oocytes: joggling a new hypothesis and old players. AB - Maternal aging adversely affects oocyte quality (function and developmental potential) and consequently lowers pregnancy rates while increasing spontaneous abortions. Substantial evidence, especially from egg donation studies, implicates the decreased quality of an aging oocyte as a major factor in the etiology of female infertility. Nevertheless, the cellular and molecular mechanisms responsible for the decreased oocyte quality with advanced maternal aging are not fully characterized. Herein we present information in the published literature and our own data to support the hypothesis that during aging induced decreases in mitochondrial ceramide levels and associated alterations in mitochondrial structure and function are prominent elements contributing to reduced oocyte quality. Hence, by examining the molecular determinants that underlie impairments in oocyte mitochondria, we expect to sieve to a better understanding of the mechanistic anatomy of oocyte aging. PMID- 22046053 TI - Caspase-mediated apoptosis of trophoblasts in term human placental villi is restricted to cytotrophoblasts and absent from the multinucleated syncytiotrophoblast. AB - Human placental villi are surfaced by a multinucleated and terminally differentiated epithelium, the syncytiotrophoblast, with a subjacent layer of mononucleated cytotrophoblasts that can divide and fuse to replenish the syncytiotrophoblast. The objectives of this study were i) to develop an approach to definitively identify and distinguish cytotrophoblasts from the syncytiotrophoblast, ii) to unambiguously determine the relative susceptibility of villous cytotrophoblasts and syncytiotrophoblast to constitutive and stress induced apoptosis mediated by caspases, and iii) to understand the progression of apoptosis in villous trophoblasts. Confocal microscopy with co-staining for E cadherin and DNA allowed us to clearly distinguish the syncytiotrophoblast from cytotrophoblasts and identified that many cytotrophoblasts are deeply interdigitated into the syncytiotrophoblast. Staining for specific markers of caspase-mediated apoptosis indicate that apoptosis occurs readily in cytotrophoblasts but is remarkably inhibited in the syncytiotrophoblast. To determine if an apoptotic cell or cell fragment was from a cytotrophoblast or syncytiotrophoblast, we found co-staining with E-cadherin along with a marker for apoptosis was essential: in the absence of E-cadherin staining, apoptotic cytotrophoblasts would easily be mistaken as representing localized regions of apoptosis in the syncytiotrophoblast. Regions with perivillous fibrin-containing fibrinoid contain the remnants of trophoblast apoptosis, and we propose this apoptosis occurs only after physical isolation of a region of the syncytium from the main body of the syncytium. We propose models for the progression of apoptosis in villous cytotrophoblasts and for why caspase-mediated apoptosis does not occur within the syncytium of placental villi. PMID- 22046056 TI - Gonadal status of male recipient mice influences germ cell development in immature buffalo testis tissue xenograft. AB - Growth and development of immature testis xenograft from various domestic mammals has been shown in mouse recipients; however, buffalo testis xenografts have not been reported to date. In this study, small fragments of testis tissue from 8 week-old buffalo calves were implanted subcutaneously onto the back of immunodeficient male mouse recipients, which were either castrated or left intact (non-castrated). The xenografts were retrieved and analyzed 12 and 24 weeks later. The grafted tissue survived and grew in both types of recipient with a significant increase in weight and seminiferous tubule diameter. Recovery of grafts from intact recipients 24 weeks post-grafting was significantly lower than that from the castrated recipients. Seminal vesicle indices and serum testosterone levels were lower in castrated recipients at both collection time points in comparison to the intact recipients and non-grafted intact mouse controls. Pachytene spermatocytes were the most advanced germ cells observed in grafts recovered from castrated recipients 24 weeks post-grafting. Complete spermatogenesis, as indicated by the presence of elongated spermatids, was present only in grafts from intact recipients collected 24 weeks post-grafting. However, significant number of germ cells with DNA damage was also detected in these grafts as indicated by TUNEL assay. The complete germ cell differentiation in xenografts from intact recipients may be attributed to efficient Sertoli cell maturation. These results suggest that germ cell differentiation in buffalo testis xenograft can be completed by altering the recipient gonadal status. PMID- 22046055 TI - Differential marker protein expression specifies rarefaction zone-containing human Adark spermatogonia. AB - It is unclear whether the distinct nuclear morphologies of human A(dark) (Ad) and A(pale) (Ap) spermatogonia are manifestations of different stages of germ cell development or phases of the mitotic cycle, or whether they may reflect still unknown molecular differences. According to the classical description by Clermont, human dark type A spermatogonium (Ad) may contain one, sometimes two or three nuclear 'vacuolar spaces' representing chromatin rarefaction zones. These structures were readily discerned in paraffin sections of human testis tissue during immunohistochemical and immunofluorescence analyses and thus represented robust morphological markers for our study. While a majority of the marker proteins tested did not discriminate between spermatogonia with and without chromatin rarefaction zones, doublesex- and mab-3-related transcription factor (DMRT1), tyrosine kinase receptor c-Kit/CD117 (KIT) and proliferation-associated antigen Ki-67 (KI-67) appeared to be restricted to subtypes which lacked the rarefaction zones. Conversely, exosome component 10 (EXOSC10) was found to accumulate within the rarefaction zones, which points to a possible role of this nuclear domain in RNA processing. PMID- 22046057 TI - Three-dimensional surface profiling and optical characterization of liquid microlens using a Shack-Hartmann wave front sensor. AB - We demonstrate three-dimensional (3D) surface profiling of the water-oil interface in a tunable liquid microlens using a Shack-Hartmann wave front sensor. The principles and the optical setup for achieving 3D surface measurements are presented and a hydrogel-actuated liquid lens was measured at different focal lengths. The 3D surface profiles are then used to study the optical properties of the liquid lens. Our method of 3D surface profiling could foster the improvement of liquid lens design and fabrication, including surface treatment and aberration reduction. PMID- 22046058 TI - Core-shell structured nanoassemblies based on beta-cyclodextrin containing block copolymer and poly(beta-benzyl L-aspartate) via host-guest complexation. AB - Double hydrophilic copolymers (PEG-b-PCDs) with one PEG block and another block containing beta-cyclodextrin (beta-CD) units were synthesized by macromolecular substitution reaction. Via a dialysis procedure, complex assemblies with a core shell structure were prepared using PEG-b-PCDs in the presence of a hydrophobic homopolymer poly(beta-benzyl L-aspartate) (PBLA). The hydrophobic PBLA resided preferably in the cores of assemblies, while the extending PEG chains acted as the outer shell. Host-guest interaction between beta-CD and hydrophobic benzyl group was found to mediate the formation of the assemblies, where PEG-b-PCD and PBLA served as the host and guest macromolecules, respectively. The particle size of the assemblies could be modulated by the composition of the host PEG-b-PCD copolymer. The molecular weight of the guest polymer also had a significant effect on the size of the assemblies. The assemblies prepared from the host and guest polymer pair were stable during a long-term storage. These assemblies could also be successfully reconstituted after freeze-drying. The assemblies may therefore be used as novel nanocarriers for the delivery of hydrophobic drugs. PMID- 22046059 TI - The Development of English Vowel Perception in Monolingual and Bilingual Infants: Neurophysiological Correlates. AB - The goal of this paper was to examine intrinsic and extrinsic factors contributing to the development of speech perception in monolingual and bilingual infants and toddlers. A substantial number of behavioral studies have characterized when infants show changes in behavior towards speech sounds in relation to amount of experience with these sounds. However, these studies cannot explain to what extent the developmental timeline is influenced by experience with the language versus constraints imposed by cortical maturation. Studies using electrophysiological measures to examine the development of auditory and speech processing have shown great differences in infant and adult electrophysiological correlates of processing. Many of these differences are a function of immature cortex in the infant. In this paper, we examined the maturation of infant and child event-related-potential (ERP) electrophysiological components in processing an English vowel contrast and explored to what extent these components are influenced by intrinsic (e.g., sex) versus extrinsic factors, such as language experience (monolingual vs. bilingual). Our findings demonstrate differences in the pattern of ERP responses related to age and sex, as well as language experience. These differences make it clear that general maturational factors need to be taken into consideration in examining the effect of language experience on the neurodevelopment of speech perception. PMID- 22046060 TI - Renal-sparing immunosuppressive protocol using OKT3 after liver transplantation: a 19-year single-institution experience. AB - Different renal-sparing immunosuppressive protocols have been used in liver transplantation. At our institution, muromonab-CD3 (OKT3) is used in patients with acute renal failure (ARF), along with a delay in starting a calcineurin inhibitor. This study was conducted to compare outcomes in liver transplant patients with ARF who received OKT3 and those who did not. From 1988 to 2007, ARF was present in 1685 of 2587 patients (65%). OKT3 was used in 109 patients (OKT3 group). The control group (1416 patients) received a low-dose calcineurin inhibitor. The OKT3 group was more critically ill. In spite of this, the OKT3 group patients who were on renal replacement therapy (RRT) achieved long-term survival similar to that of the control group on RRT. Among the patients who were not on RRT, the OKT3 group had a higher complete recovery rate, but this did not translate into improved long-term survival. Bacterial and fungal infections were more common in the OKT3 group; however, there was no increased risk of malignancy or death from hepatitis C recurrence. The use of OKT3 in patients with ARF allowed more critically ill patients on RRT to achieve survival rates similar to those of patients who did not receive OKT3. PMID- 22046061 TI - Carotid resection and reconstruction associated with treatment of head and neck cancer. AB - Patients with head and neck cancer may experience carotid artery involvement. We present a series of 10 patients, all with stage IVB disease, who required carotid resection and reconstruction to achieve a complete resection. Nine of the 10 patients had previous radiation treatment to the neck. Six died of distant disease, and three died of other causes with no local or regional recurrences. Carotid resection and reconstruction can be done safely, achieving local and regional control. PMID- 22046062 TI - The preadmission packet: a strategy that benefits patients and nurses during the admission process. AB - At Baylor Jack and Jane Hamilton Heart and Vascular Hospital, we developed a preadmission packet that is given to patients before their procedure date, enabling them to complete much of their paperwork in advance. The results of our subsequent study revealed that nurses save time during the assessment interview when patients arrive at the hospital with their admission database forms completed. In a busy facility with a large number of patients admitted daily, the nursing time saved can translate into a substantial economic benefit. Even more important, however, is the benefit to patients, who feel less rushed and provide a more thorough and accurate medical history when they can fill out the admission database form at home. PMID- 22046063 TI - Multiple myeloma presenting as acute renal failure. PMID- 22046064 TI - Granulocytic sarcoma and HIV. AB - Hematopoietic neoplasms are known to occur in the setting of HIV. Excluding Kaposi's sarcoma, the neoplasms are generally high-grade lymphoproliferative disorders. Granulocytic sarcoma, an extramedullary hematopoietic malignancy that may precede or occur during the course of acute myeloid leukemia, has rarely been described in the HIV population. We present the fourth documented case, to our knowledge, of a granulocytic sarcoma occurring in an HIV-positive individual. This has been associated with a very poor prognostic outcome. PMID- 22046065 TI - Coronary angiography and computed tomography in situs inversus totalis. PMID- 22046066 TI - Journey to the Borderland: Baylor's Faith in Action Initiative's donation of medical equipment to Ukraine. PMID- 22046067 TI - Comfort and caring at the end of life: Baylor's doula program. PMID- 22046068 TI - Victorian origins of William Osler's philosemitism? PMID- 22046069 TI - Rubber gloves redux. PMID- 22046070 TI - Harold Clifton Urschel III, MD: an interview with the editor on his passion to prevent and cure addiction. PMID- 22046072 TI - Remembrances of dr. Billie aronoff. PMID- 22046071 TI - A tribute to John Capehart, MD, "Sooner proud" and 1961 National Spelling Bee champion. PMID- 22046073 TI - Electrocardiogram of a man with a single-chamber cardioverter/defibrillator. PMID- 22046074 TI - Primary cutaneous large B-cell lymphoma, leg type. AB - Primary cutaneous large B-cell lymphoma, leg type, is a rare and aggressive neoplasm as defined by the recently updated World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. We present a case of a 74-year-old woman who presented with a cutaneous lesion on her forearm. Skin biopsy revealed pathology consistent with this entity. The patient was treated with systemic chemotherapy with rituximab combined with doxorubicin, cyclophosphamide, vincristine, and prednisone. Here, we review the available literature and summarize clinical features and management of this uncommon subtype of non-Hodgkin lymphoma. PMID- 22046075 TI - A tracheal lesion simulating an aneurysmal bone cyst. PMID- 22046076 TI - Splenic hemangiomatosis. PMID- 22046077 TI - Positron emission tomography-computed tomography of esophageal adenocarcinoma with vascular invasion and tumor thrombus. PMID- 22046078 TI - New provisions regarding Texas Medical Board proceedings. PMID- 22046079 TI - Facts and ideas from anywhere. PMID- 22046080 TI - NF-kappaB signaling in the brain of autistic subjects. AB - Autism is a neurodevelopmental disorder characterized by problems in communication, social skills, and repetitive behavior. Recent studies suggest that apoptotic and inflammatory mechanisms may contribute to the pathogenesis of this disorder. Nuclear factor-kappaB (NF-kappaB) is an important gene transcriptional factor involved in the mediation of inflammation and apoptosis. This study examined the activities of the NF-kappaB signaling pathway in the brain of autistic subjects and their age-matched controls. The NF-kappaB activation is also determined in the brain of BTBR mice, which is a promising animal model for study of pathogenic mechanisms responsible for autism. Our results showed that the level of IKKalpha kinase, which phosphorylates the inhibitory subunit IkappaBalpha, is significantly increased in the cerebellum of autistic subjects. However, the expression and phosphorylation of IkappaBalpha are not altered. In addition, our results demonstrated that the expression of NF kappaB (p65), and the phosphorylation/activation of NF-kappaB (p65) at Ser536 are not significantly changed in the cerebellum and cortex of both autistic subjects and BTBR mice. Our findings suggest that the NF-kappaB signaling pathway is not disregulated in the brain of autistic subjects and thus may not be significantly involved in the processes of abnormal inflammatory responses suggested in autistic brain. PMID- 22046081 TI - Inhalative IL-10 attenuates pulmonary inflammation following hemorrhagic shock without major alterations of the systemic inflammatory response. AB - Several studies report immunomodulatory effects of endogenous IL-10 after trauma. The present study investigates the effect of inhalative IL-10 administration on systemic and pulmonary inflammation in hemorrhagic shock. Male C57/BL6 mice (8 animals per group) were subjected to pressure-controlled hemorrhagic shock for 1.5 hrs followed by resuscitation and inhalative administration of either 50 MUL PBS (Shock group) or 50 MUg/kg recombinant mouse IL-10 dissolved in 50 MUL PBS (Shock + IL-10 group). Animals were sacrificed after 4.5 hrs of recovery and serum IL-6, IL-10, KC, and MCP-1 concentrations were measured with ELISA kits. Acute pulmonary inflammation was assessed by pulmonary myeloperoxidase (MPO) activity and pulmonary H&E histopathology. Inhalative IL-10 administration decreased pulmonary inflammation without altering the systemic concentrations of IL-6, IL-10, and KC. Serum MCP-1 levels were significantly reduced following inhalative IL-10 administration. These findings suggest that inhalative IL-10 administration may modulate the pulmonary microenvironment without major alterations of the systemic inflammatory response, thus minimizing the potential susceptibility to infection and sepsis. PMID- 22046082 TI - Update on endoscopic pancreatic function testing. AB - Hormone-stimulated pancreatic function tests (PFTs) are considered the gold standard for measuring pancreatic exocrine function. PFTs involve the administration of intravenous secretin or cholecystokinin, followed by collection and analysis of pancreatic secretions. Because exocrine function may decline in the earliest phase of pancreatic fibrosis, PFTs are considered accurate for diagnosing chronic pancreatitis. Unfortunately, these potentially valuable tests are infrequently performed except at specialized centers, because they are time consuming and complicated. To overcome these limitations, endoscopic PFT methods have been developed which include aspiration of pancreatic secretions through the suction channel of the endoscope. The secretin endoscopic pancreatic function test (ePFT) involves collection of duodenal aspirates at 15, 30, 45 and 60 min after secretin stimulation. A bicarbonate concentration greater than 80 mmol/L in any of the samples is considered a normal result. The secretin ePFT has demonstrated good sensitivity and specificity compared with various reference standards, including the "Dreiling tube" secretin PFT, endoscopic ultrasound, and surgical histology. Furthermore, a standard autoanalyzer can be used for bicarbonate analysis, which allows the secretin ePFT to be performed at any hospital. The secretin ePFT may complement imaging tests like endoscopic ultrasound (EUS) in the diagnosis of early chronic pancreatitis. This paper will review the literature validating the use of ePFT in the diagnosis of exocrine insufficiency and chronic pancreatitis. Newer developments will also be discussed, including the feasibility of combined EUS/ePFT, the use of cholecystokinin alone or in combination with secretin, and the discovery of new protein and lipid pancreatic juice biomarkers which may complement traditional fluid analysis. PMID- 22046083 TI - Ankaferd hemostat in the management of gastrointestinal hemorrhages. AB - Gastrointestinal (GI) bleeding refers to any hemorrhage ascribed to the pathologies of the gastrointestinal tract, extending from the mouth to the anal canal. Despite the recent improvements in the endoscopic, hemostatic and adjuvant pharmacologic techniques, the reported mortality is still around 5%-10% for peptic ulcer bleeding and about 15%-20% for variceal hemorrhages. Although endoscopic management reduces the rates of re-bleeding, surgery, and mortality in active bleeding; early recurrence ratios still occur in around 20% of the cases even with effective initial hemostatic measures. In this quest for an alternative pro-hemostatic agent for the management of GI bleedings, Ankaferd blood stopper (ABS) offers a successful candidate, specifically for "difficult-to-manage" situations as evidenced by data presented in several studies. ABS is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. It is effective in both bleeding individuals with normal hemostatic parameters and in patients with deficient primary and/or secondary hemostasis. ABS also modulates the cellular apoptotic responses to hemorrhagic stress, as well as hemostatic hemodynamic activity. Through its effects on the endothelium, blood cells, angiogenesis, cellular proliferation, vascular dynamics, and wound healing, ABS is now becoming an effective alternative hemostatic medicine for gastrointestinal bleedings that are resistant to conventional anti-hemorrhagic measurements. The aim of this review is to outline current literature experience suggesting the place of ABS in the management of GI bleeding, and potential future controlled trials in this complicated field. PMID- 22046084 TI - A new look at anti-Helicobacter pylori therapy. AB - With the rising prevalence of antimicrobial resistance, the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e., 80% or less) in most countries. Therefore, several treatment regimens have emerged to cure Helicobacter pylori (H. pylori) infection. Novel first-line anti-H. pylori therapies in 2011 include sequential therapy, concomitant quadruple therapy, hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy. After the failure of standard triple therapy, a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI), bismuth, tetracycline and metronidazole can be employed as rescue treatment. Recently, triple therapy combining a PPI, levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy. This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects. The best second-line therapy for patients who fail to eradicate H. pylori with first-line therapies containing clarithromycin, amoxicillin and metronidazole is unclear. However, a levofloxacin-based triple therapy is an accepted rescue treatment. Most guidelines suggest that patients requiring third line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test. Nonetheless, an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H. pylori infection if antimicrobial sensitivity data are unavailable. PMID- 22046085 TI - MicroRNAs as a potential prognostic factor in gastric cancer. AB - AIM: To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer. METHODS: The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available. Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples, preserving the small RNA fraction. Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection. The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group, n = 14, 31%) and those who did not (good-prognosis group, n = 31, 69%). RESULTS: Three miRs, miR-451, miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P < 0.0002, 0.0027 and 0.0046 respectively). High expression of each miR was associated with poorer prognosis for both recurrence and survival. Using miR-451, the positive predictive value for non-recurrence was 100% (13/13). The expression of the differential miRs was verified by qRT-PCR, showing high correlation to the microarray data and similar separation into prognosis groups. CONCLUSION: This study identified three miRs, miR-451, miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer. Of these, miR-451 had the strongest prognostic impact. PMID- 22046086 TI - Dynamic changes and surveillance function of prion protein expression in gastric cancer drug resistance. AB - AIM: To explore the dynamic changes of prion protein (PrPc) in the process of gastric cancer drug resistance and the role of PrPc expression in the prognosis of gastric cancer patients receiving chemotherapy. METHODS: A series of gastric cancer cell lines resistant to different concentrations of adriamycin was established, and the expression of PrPc, Bcl-2 and Bax was detected in these cells. Apoptosis was determined using Annexin V staining. Western blotting and immunohistochemistry were performed to detect the expression of PrPc in patients receiving chemotherapy and to explore the role of PrPc expression in predicting the chemosensitivity and the outcome of gastric cancer patients receiving chemotherapy. Follow-up was performed for 2 years. RESULTS: PrPc expression was increased with the increase in drug resistance. Bcl-2, together with PrPc, increased the level of anti-apoptosis of cancer cells. Increased PrPc expression predicted the enhanced level of anti-apoptosis and resistance to anticancer drugs. PrPc expression could be used as a marker for predicting the efficacy of chemotherapy and the prognosis of gastric cancer. Increased PrPc expression predicted both poor chemosensitivity and a low 2-year survival rate. Contrarily, low PrPc expression predicted favorable chemosensitivity and a relatively high 2 year survival rate. CONCLUSION: PrPc expression is associated with histological types and differentiation of gastric cancer cells; The PrPc expression level might be a valuable marker in predicting the efficacy of chemotherapy and the prognosis of gastric cancer patients receiving chemotherapy. PMID- 22046087 TI - Association of overexpression of TIF1gamma with colorectal carcinogenesis and advanced colorectal adenocarcinoma. AB - AIM: To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1gamma), Smad4 and transforming growth factor beta (TGFbetaR) across a spectrum representing colorectal cancer (CRC) development. METHODS: Tissue microarrays were prepared from archival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1gamma, Smad4 and TGFbetaRII. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4). RESULTS: Overexpression of TIF1gamma was detected in 5/26 (19%) HP; however, it was seen in a significantly higher proportion of neoplasms, 15/25 (60%) TAs and 24/51 (47%) CRCs (P < 0.05). Normal colonic mucosa, HP, and TAs showed strong Smad4 expression, while its expression was absent in 22/51 (43%) CRCs. Overexpression of TGFbetaRII was more commonly seen in neoplasms, 13/25 (52%) TAs and 29/51 (57%) CRCs compared to 9/26 (35%) HP (P < 0.05). Furthermore, there was a correlation between TIF1gamma overexpression and Smad4 loss in CRC (Kendall tau rank correlation value = 0.35, P < 0.05). The levels of TIF1gamma overexpression were significantly higher in stage III than in stage I and II CRC (P < 0.05). CONCLUSION: The findings suggest that over-expression of TIF1gamma occurs in early stages of colorectal carcinogenesis, is inversely related with Smad4 loss, and may be a prognostic indicator for poor outcome. PMID- 22046088 TI - Role of high definition colonoscopy in colorectal adenomatous polyp detection. AB - AIM: To investigate the rates of polyp detection in a mixed risk population using standard definition (SDC) vs high definition colonoscopes (HDC). METHODS: This was a retrospective cohort comparative study of 3 colonoscopists who each consecutively performed 150 SDC (307, 200 pixel) and 150 HDC (792, 576 pixels) in a community teaching hospital. RESULTS: A total of 900 colonoscopies were evaluated (mean age 56, 46.8% men), 450 with each resolution. Polyps of any type were detected in 46.0% of patients using SDC and 43.3% with HDC (P = 0.42). There was no significant difference between the overall number of polyps, HDC (397) and SDC (410), detected among all patients examined, (P = 0.73). One or more adenomatous polyps were detected in 24.2% of patients with HDC and 24.9% of patients with SDC colonoscopy (P = 0.82). There was no significant difference between HDC (M = 0.41) and SDC (M = 0.42) regarding adenomatous polyp (P = 0.88) or advanced adenoma (P = 0.56) detection rate among all patients examined. CONCLUSION: HDC did not improve yield of adenomatous polyp, advanced adenoma or overall polyp detection in a population of individuals with mixed risk for colorectal cancer. PMID- 22046089 TI - Does N ratio affect survival in D1 and D2 lymph node dissection for gastric cancer? AB - AIM: To identify whether there could have been changes in survival if lymph node ratio (N ratio) had been used. METHODS: We assessed 334 gastric adenocarcinoma cases retrospectively between 2001 and 2009. Two hundred and sixteen patients out of 334 were included in the study. Patients were grouped according to disection1 (D1) or dissection 2 (D2) dissection. We compared the estimated survival and actual survival determined by Pathologic nodes (pN) class and N ratio, and SPSS 15.0 software was used for statistical analysis. RESULTS: Ninety-six (44.4%) patients underwent D1 dissection and 120 (55.6%) had D2 dissection. When groups were evaluated, 23 (24.0%) patients in D1 and 21 (17.5%) in D2 had stage migration (P = 0.001). When both D1 and D2 groups were evaluated for number of pathological lymph nodes, despite the fact that there was no difference in N ratio between D1 and D2 groups, a statistically significant difference was found between them with regard to pN1 and pN2 groups (P = 0.047, P = 0.044 respectively). In D1, pN0 had the longest survival while pN3 had the shortest. In D2, pN0 had the longest survival whereas pN3 had the shortest survival. CONCLUSION: N ratio is an accurate staging system for defining prognosis and treatment plan, thus decreasing methodological errors in gastric cancer staging. PMID- 22046090 TI - Practical approaches to effective management of intestinal radiation injury: benefit of resectional surgery. AB - AIM: To study the outcome of patients undergoing surgical resection of the bowel for sustained radiation-induced damage intractable to conservative management. METHODS: During a 7-year period we operated on 17 cases (5 male, 12 female) admitted to our surgical department with intestinal radiation injury (IRI). They were originally treated for a pelvic malignancy by surgical resection followed by postoperative radiotherapy. During follow-up, they developed radiation enteritis requiring surgical treatment due to failure of conservative management. RESULTS: IRI was located in the terminal ileum in 12 patients, in the rectum in 2 patients, in the descending colon in 2 patients, and in the cecum in one patient. All patients had resection of the affected region(s). There were no postoperative deaths, while 3 cases presented with postoperative complications (17.7%). All patients remained free of symptoms without evidence of recurrence of IRI for a median follow-up period of 42 mo (range, 6-96 mo). CONCLUSION: We report a favorable outcome without IRI recurrence of 17 patients treated by resection of the diseased bowel segment. PMID- 22046092 TI - Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma. AB - AIM: To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma. METHODS: One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1 4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4. RESULTS: Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T stage (P = 0.053). Coexistent nuclear localization of DLL4 was related to poor survival (P = 0.002). CONCLUSION: Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma. PMID- 22046091 TI - Corticotropin-releasing factor secretion from dendritic cells stimulated by commensal bacteria. AB - AIM: To study the production and secretion of corticotropin-releasing factor (CRF) by dendritic cells and the influence of commensal bacteria. METHODS: JAWSII cells (ATCC CRL-11904), a mouse dendritic cell line, were seeded into 24-well culture plates and grown for 3 d. Commensal bacterial strains of Clostridium clostrodiiforme (JCM1291), Bacteroides vulgatus (B. vulgatus) (JCM5856), Escherichia coli (JCM1649), or Fusobacterium varium (F. varium) (ATCC8501) were added to the cells except for the control well, and incubated for 2 h. After incubation, we performed enzyme-linked immunosorbent assay for the cultured medium and reverse transcription polymerase chain reaction for the dendritic cells, and compared these values with controls. RESULTS: The level of CRF secretion by control dendritic cells was 40.4 +/- 6.2 pg/mL. The CRF levels for cells incubated with F. varium and B. vulgatus were significantly higher than that of the control (P < 0.0001). CRF mRNA was present in the control sample without bacteria, and CRF mRNA levels in all samples treated with bacteria were above that of the control sample. F. varium caused the greatest increase in CRF mRNA expression. CONCLUSION: Our results suggest that dendritic cells produce CRF, a process augmented by commensal bacteria. PMID- 22046093 TI - Metabolic syndrome, lifestyle risk factors, and distal colon adenoma: a retrospective cohort study. AB - AIM: To investigate relationships between colorectal adenoma incidence, metabolic syndrome (MS) components and lifestyle factors. METHODS: We conducted a retrospective cohort study using data from individuals who had multiple sigmoidoscopies for colon cancer at the Health Promotion Center of Ulsan University Hospital in Korea from 1998 to 2007. RESULTS: By multivariate analysis, the incidence of distal colon adenoma was increased by more than 1.76 times in individuals with at least one component of MS compared to those without a component of MS. After adjustment for age, gender, smoking, drinking, and physical exercise, only high body mass index (BMI) was significantly associated with the incidence of distal colon adenoma (Hazard ratio 1.66, 95% confidence interval 1.05-2.62). CONCLUSION: Our results suggest that high BMI may increase the risk of colorectal adenoma in Korean adults. PMID- 22046094 TI - Neoplasm-like abdominal nonhematogenous disseminated tuberculous lymphadenopathy: CT evaluation of 12 cases and literature review. AB - AIM: To assess the diagnostic value of computed tomography (CT) imaging in screening for abdominal nonhematogenous disseminated tuberculous lymphadenopathy (TL). METHODS: The CT scans of 12 patients with abdominal nonhematogenous disseminated TL suggestive of neoplasm were retrospectively analyzed in this review. The final diagnoses were confirmed by lymph node pathology for seven patients and by laparoscopic surgery for five patients. All of the patients were treated at our institution between April 1995 and August 2009. RESULTS: The sites of involvement were the periportal (n = 6), peripancreatic (n = 3), periaortic (n = 3), and mesenteric (n = 2) regions. On the plain CT scan, the lymphadenopathy showed a heterogeneous isodensity or hypodensity in 11 patients and a low density in one patient. Peripheral enhancement was observed on the dynamic contrast enhanced CT scans for all patients. In two cases, scans were more revealing during the portal venous and delayed phases. CONCLUSION: Abdominal lymphadenopathy with predominant peripheral rim-like enhancement on the dynamic contrast-enhanced CT scan may suggest a diagnosis of TL. PMID- 22046095 TI - Collagen-based biological glue after Appleby operation for advanced gastric cancer. AB - Pancreatic fistula is a common complication of distal pancreatectomy; although various surgical procedures have been proposed, no clear advantage is evident for a single technique. We herein report the case of a 38-year-old patient affected by an advanced gastric carcinoma infiltrating the pancreas body, with extensive nodal metastases involving the celiac trunk, who underwent total gastrectomy with lymphadenectomy, distal pancreatectomy and resection en bloc of the celiac trunk (Appleby operation). At the end of the demolitive phase, the pancreatic stump and the aorta at the level of the celiac ligature were covered with a layer of Tachosil((r)), a horse collagen sponge made with human coagulation factors (fibrinogen and thrombin). Presenting this case, we wish to highlight the possible sealing effect of this product and hypothesize a role in preventing pancreatic fistula and postoperative lymphorrhagia from extensive nodal dissection. PMID- 22046096 TI - Esophageal mucosal lesion with low-dose aspirin and prasugrel mimics malignancy: a case report. AB - Dual antiplatelet therapy consisting of low-dose aspirin (LDA) and other antiplatelet medications is recommended in patients with coronary heart disease, but it may increase the risk of esophageal lesion and bleeding. We describe a case of esophageal mucosal lesion that was difficult to distinguish from malignancy in a patient with a history of ingesting LDA and prasugrel after implantation of a drug-eluting stent. Multiple auxiliary examinations were performed to make a definite diagnosis. The patient recovered completely after concomitant acid-suppressive therapy. Based on these findings, we strongly argue for the evaluation of the risk of gastrointestinal mucosal injury and hemorrhage if LDA therapy is required, and we stress the paramount importance of using drug combinations in individual patients. PMID- 22046097 TI - Hypergastrinemia and recurrent type 1 gastric carcinoid in a young Indian male: necessity for antrectomy? AB - Carcinoid tumors are the most common neuroendocrine tumors. Gastric carcinoids represent 2% of all carcinoids and 1% of all gastric masses. Due to the widespread use of Esophagogastroduodenoscopy for evaluating a variety of upper gastrointestinal symptoms, the detection of early gastric carcinoids has increased. We highlight an alternative management of a young patient with recurrent type 1 gastric carcinoids with greater than 5 lesions, as well as lesions intermittently greater than 1 cm. Gastric carcinoids have a variable presentation and clinical course that is highly dependent on type. Type 1 gastric carcinoids are usually indolent and have a metastasis rate of less than 2%, even with tumors larger than 2 cm. There are a number of experts as well as organizations that recommend endoscopic resection for all type 1 gastric carcinoid lesions less than 1 cm, with a follow-up every 6-12 mo. They also recommend antrectomy for type 1 gastric carcinoids with greater than 5 lesions, lesions 1 cm or greater, or refractory anemia. However, the American Society of Gastrointestinal Endoscopy guidelines state that type 1 gastric carcinoid surveillance is controversial based on the evidence and could not make an evidence-based position statement on the best treatment modality. Our report illustrates a rare cause of iron deficiency anemia in a young male (without any medical history) due to multiple recurrent gastric carcinoid type 1 lesions in the setting of atrophic gastritis causing hypergastrinemia, and in the absence of a vitamin B12 deficiency. Gastric carcinoid type 1 can present in young males without an autoimmune history, despite the known predilection for women aged 50 to 70 years. Type 1 gastric carcinoids can be managed by endoscopic resection in patients with greater than 5 lesions, even with lesions larger than 1 cm. This course of treatment enabled the avoidance of early antrectomy in our patient, who expressed a preference against more invasive measures at his young age. PMID- 22046098 TI - Electro-worming: The behaviors of Caenorhabditis (C.) elegans in DC and AC electric fields. PMID- 22046099 TI - Possible linkage of SP6 transcriptional activity with amelogenesis by protein stabilization. AB - Ameloblasts produce enamel matrix proteins such as amelogenin, ameloblastin, and amelotin during tooth development. The molecular mechanisms of ameloblast differentiation (amelogenesis) are currently not well understood. SP6 is a transcription factor of the Sp/KLF family that was recently found to regulate cell proliferation in a cell-type-specific manner. Sp6-deficient mice demonstrate characteristic tooth anomalies such as delayed eruption of the incisors and supernumerary teeth with disorganized amelogenesis. However, it remains unclear how Sp6 controls amelogenesis. In this study, we used SP6 high producer cells to identify SP6 target genes. Based on the observations that long-term culture of SP6 high producer cells reduced SP6 protein expression but not Sp6 mRNA expression, we found that SP6 is short lived and specifically degraded through a proteasome pathway. We established an in vitro inducible SP6 expression system coupled with siRNA knockdown and found a possible linkage between SP6 and amelogenesis through the regulation of amelotin and Rock1 gene expression by microarray analysis. Our findings suggest that the regulation of SP6 protein stability is one of the crucial steps in amelogenesis. PMID- 22046100 TI - Role of Shwachman-Bodian-Diamond syndrome protein in translation machinery and cell chemotaxis: a comparative genomics approach. AB - Shwachman-Bodian-Diamond syndrome (SBDS) is linked to a mutation in a single gene. The SBDS proinvolved in RNA metabolism and ribosome-associated functions, but SBDS mutation is primarily linked to a defect in polymorphonuclear leukocytes unable to orient correctly in a spatial gradient of chemoattractants. Results of data mining and comparative genomic approaches undertaken in this study suggest that SBDS protein is also linked to tRNA metabolism and translation initiation. Analysis of crosstalk between translation machinery and cytoskeletal dynamics provides new insights into the cellular chemotactic defects caused by SBDS protein malfunction. The proposed functional interactions provide a new approach to exploit potential targets in the treatment and monitoring of this disease. PMID- 22046101 TI - The role of galenic innovation in improving treatment compliance and persistence: three case studies. AB - BACKGROUND: The purpose of this study was to explore whether newer galenic formulations with lower treatment burdens are associated with better patient compliance and persistence compared with older more burdensome modalities. METHODS: Data from the IMS Disease Analyzer database were analyzed retrospectively for two pairs of analogs (alendronate sodium once daily vs once weekly and immediate-release vs extended-release methylphenidate) and one pair of drugs with similar indications but important differences in convenience and dosing instructions (desferrioxamine vs deferasirox). Compliance was calculated as the sum of prescription durations for all prescriptions for each patient over 1 year. Persistence was calculated as the time between first and last prescriptions over 2 years (1 year for deferasirox and desferrioxamine). Data from Germany and the UK were available and used for analysis. RESULTS: Incremental improvements in compliance were +30% in the UK and +26% in Germany for alendronate once weekly vs once daily, +14% in the UK and +19% in Germany for extended-release vs immediate-release methylphenidate, and +15% in Germany for desferrioxamine vs deferasirox. Incremental improvements in persistence were +9 months in the UK and +8 months in Germany for alendronate once weekly vs once daily, +4 months in the UK and +3 months in Germany for extended-release vs immediate-release methylphenidate, and +2 months in Germany for deferasirox vs desferrioxamine. CONCLUSION: The new formulations that we evaluated were associated with better compliance and persistence compared with older formulations. Despite the fact that some sources of bias could not be excluded, it is likely that these improvements can be attributed to the lower treatment burdens of the galenic formulations of the drugs considered. Further investigation is required to confirm these findings and to determine whether new galenic formulations can improve health outcomes in routine clinical practice. PMID- 22046102 TI - Role of centralized review processes for making reimbursement decisions on new health technologies in Europe. AB - BACKGROUND: The purpose of this study was to compare centralized reimbursement/coverage decision-making processes for health technologies in 23 European countries, according to: mandate, authority, structure, and policy options; mechanisms for identifying, selecting, and evaluating technologies; clinical and economic evidence expectations; committee composition, procedures, and factors considered; available conditional reimbursement options for promising new technologies; and the manufacturers' roles in the process. METHODS: A comprehensive review of publicly available information from peer-reviewed literature (using a variety of bibliographic databases) and gray literature (eg, working papers, committee reports, presentations, and government documents) was conducted. Policy experts in each of the 23 countries were also contacted. All information collected was reviewed by two independent researchers. RESULTS: Most European countries have established centralized reimbursement systems for making decisions on health technologies. However, the scope of technologies considered, as well as processes for identifying, selecting, and reviewing them varies. All systems include an assessment of clinical evidence, compiled in accordance with their own guidelines or internationally recognized published ones. In addition, most systems require an economic evaluation. The quality of such information is typically assessed by content and methodological experts. Committees responsible for formulating recommendations or decisions are multidisciplinary. While criteria used by committees appear transparent, how they are operationalized during deliberations remains unclear. Increasingly, reimbursement systems are expressing interest in and/or implementing reimbursement policy options that extend beyond the traditional "yes," "no," or "yes with restrictions" options. Such options typically require greater involvement of manufacturers which, to date, has been limited. CONCLUSION: Centralized reimbursement systems have become an important policy tool in many European countries. Nevertheless, there remains a lack of transparency around critical elements, such as how multiple factors or criteria are weighed during committee deliberations. PMID- 22046104 TI - Impact of early intervention and disease modification in patients with predementia Alzheimer's disease: a Markov model simulation. AB - BACKGROUND: Early screenings involving biomarkers and use of potential disease modifying therapies (DMTs) may have significant humanistic implications for treatment strategies in Alzheimer's disease. METHODS: Markov models simulated transitions of patient cohorts beginning in predementia, a hypothetical early stage of Alzheimer's disease marked by objective cognitive impairment/memory complaints without functional impairment, and followed for 10 years. Hypothetical cohorts of 10,000 patients included those who were treated with standard of care (donepezil) upon reaching mild-moderate Alzheimer's disease, a DMT in predementia, and a DMT in mild-moderate Alzheimer's disease. Transition probabilities were based on data from the Alzheimer's Disease Neuroimaging Initiative and published clinical data, and estimated for the hypothetical DMT. In each disease stage (predementia, mild, moderate, or severe), time was computed and costs were estimated using literature review and published data, and published data provided mortality rates. The impact of screening was evaluated using positive predictive value (patients identified as predementia truly at risk for transition to dementia). RESULTS: Earlier treatment yielded modest gains in total life-years; however, the distribution was skewed towards milder disease. Assuming a 25% reduction in the annual risk of progression, treating predementia patients with DMT increased life-years in predementia to mild states on average from 3.2 to 4.2, while life-years spent in moderate-to-severe Alzheimer's disease decreased from 2.6 to 2.2. Average time in the community increased from 4.4 to 5.4 years, while time in long-term care declined from 1.3 to 0.9 years. This impact grows as the advantage of the novel agent increases. Screening accuracy had significant implications for cost-effectiveness. CONCLUSION: If screening can accurately identify predementia patients at risk for progression, earlier treatment with DMTs has the potential benefit to patients of prolonging time in milder disease, reducing time spent with more severe disease, increasing time in the community, and reducing time in long-term care. PMID- 22046105 TI - Relationship between leukotriene-modifying agent prescriptions dispensed and rate of suicide deaths by county in the US. AB - BACKGROUND: The US Food and Drug Administration has issued warnings about a potential link between leukotriene receptor-modifying agents (LTMA) and suicide. These warnings are based on case reports and there is controversy about the association. While spontaneous reporting of suicide-related events attributed to LTMA has risen dramatically, these data may be biased by the warnings. The objective of this study was to explore the relationship between LTMA and suicide deaths using event data preceding the Food and Drug Administration warnings. METHODS: We conducted a mixed-effects Poisson regression analysis of the association between LTMA prescriptions dispensed and suicide deaths at the county level. Counts of suicide deaths in each US county, stratified by race, age group, gender, and year were obtained from the National Center for Health Statistics for the period January 1, 1999 to December 31, 2006. Counts of LTMA prescriptions dispensed in each US county were obtained from IMS Health Incorporated. The model estimated the overall suicide rate conditional on LTMA use, adjusted for age, gender, race, year, and antidepressant utilization. We also assessed the intracounty and intercounty associations. RESULTS: There were 249,872 suicides in the US between 1999 and 2006, and the annual suicide rate ranged from 11.17 to 11.92 per 100,000 population. There were 118.63, 11.68, and 0.12 million prescriptions dispensed for montelukast, zafirlukast, and zileuton, respectively, between 1999 and 2006. The mean rate of LTMA prescriptions dispensed by county was 42.91 (95% confidence interval [CI] 42.78-43.04), 4.82 (95% CI 4.81-4.84), and 0.05 (95% CI 0.05-0.05) per 1000 for montelukast, zafirlukast, and zileuton, respectively. We found a negative within-county association between the rate of total LTMA prescriptions dispensed and the suicide rate by county (P = 0.0296). This association was primarily driven by montelukast. CONCLUSION: Our results, while subject to certain limitations, provide preliminary evidence that the association between LTMA and suicide could be different (ie, reduced risk) than that which might be anticipated based on previous warnings. Patient-level research is needed to understand more clearly the association between LTMA and suicide. PMID- 22046106 TI - Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study. AB - BACKGROUND: The 5-hydroxytryptamine type 3 antagonists, or setrons (eg, ondansetron), are commonly used for nausea and vomiting in the hospital setting. In 2001, droperidol was given a black box warning because it was found to prolong the QT interval and induce arrhythmias. The setrons share with droperidol the same potential proarrhythmic mechanisms, but limited data exist concerning their effects on the QT interval in individuals at high risk for torsades de pointes. METHODS: Forty hospitalized patients admitted for heart failure or acute coronary syndromes with one or more risk factors for torsades de pointes and an order for intravenous ondansetron 4 mg were enrolled in this prospective, observational study. The QT interval corrected for heart rate (QTc) was obtained via a 12-lead electrocardiogram on admission and again 120 minutes after the first dose of ondansetron in order to determine the mean change in QTc following ondansetron exposure. RESULTS: The mean time interval between obtaining the baseline electrocardiogram and the second electrocardiogram following ondansetron administration was 3.5 +/- 2.14 hours. In the total population, the QTc interval was prolonged by 19.3 +/- 18 msec (P < 0.0001) 120 minutes after ondansetron administration. For patients with an acute coronary syndrome and those with heart failure, QTc was prolonged by 18.3 +/- 20 msec (P < 0.0001) and 20.6 +/- 20 msec (P < 0.0012), respectively. Following ondansetron exposure, 31% and 46% in the heart failure and acute coronary syndromes groups, respectively, met gender related thresholds for a prolonged QTc. CONCLUSION: Our study found QTc prolongation due to ondansetron administration similar to that found in previous studies. When used in patients with cardiovascular disease (eg, heart failure or acute coronary syndromes) with one or more risk factors for torsades de pointes, ondansetron may significantly increase the QTc interval for up to 120 minutes after administration. From a patient safety perspective, patients who are at high risk for torsades de pointes and receiving ondansetron should be followed via telemetry when admitted to hospital. PMID- 22046107 TI - Cumulative clinical experience from over a decade of use of levofloxacin in community-acquired pneumonia: critical appraisal and role in therapy. AB - Levofloxacin is the synthetic L-isomer of the racemic fluoroquinolone, ofloxacin. It interferes with critical processes in the bacterial cell such as DNA replication, transcription, repair, and recombination by inhibiting bacterial topoisomerases. Levofloxacin has broad spectrum activity against several causative bacterial pathogens of community-acquired pneumonia (CAP). Oral levofloxacin is rapidly absorbed and is bioequivalent to the intravenous formulation such that patients can be conveniently transitioned between these formulations when moving from the inpatient to the outpatient setting. Furthermore, levofloxacin demonstrates excellent safety, and has good tissue penetration maintaining adequate concentrations at the site of infection. The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in patients with CAP are well established. Furthermore, a high-dose (750 mg) and short-course (5 days) of once-daily levofloxacin has been approved for use in the US in the treatment of CAP, acute bacterial sinusitis, acute pyelonephritis, and complicated urinary tract infections. The high-dose, short-course levofloxacin regimen maximizes its concentration-dependent antibacterial activity, decreases the potential for drug resistance, and has better patient compliance. PMID- 22046108 TI - Improved Binding Free Energy Predictions from Single-Reference Thermodynamic Integration Augmented with Hamiltonian Replica Exchange. AB - Reliable predictions of relative binding free energies are essential in drug discovery, where chemists modify promising compounds with the aim of increasing binding affinity. Conventional Thermodynamic Integration (TI) approaches can estimate corresponding changes in binding free energies, but suffer from inadequate sampling due to ruggedness of the molecular energy surfaces. Here, we present an improved TI strategy for computing relative binding free energies of congeneric ligands. This strategy employs a specific, unphysical single-reference (SR) state and Hamiltonian replica exchange (HREX) to locally enhance sampling. We then apply this strategy to compute relative binding free energies of twelve ligands in the L99A mutant of T4 Lysozyme. Besides the ligands, our approach enhances hindered rotations of the important V111, as well as V87 and L118 sidechains. Concurrently, we devise practical strategies to monitor and improve HREX-SRTI efficiency. Overall, the HREX-SRTI results agree well (R(2) = 0.76, RMSE = 0.3 kcal/mol) with available experimental data. When optimized for efficiency, the HREX-SRTI precision matches that of experimental measurements. PMID- 22046109 TI - BioStar: an online question & answer resource for the bioinformatics community. PMID- 22046110 TI - Receptive field inference with localized priors. AB - The linear receptive field describes a mapping from sensory stimuli to a one dimensional variable governing a neuron's spike response. However, traditional receptive field estimators such as the spike-triggered average converge slowly and often require large amounts of data. Bayesian methods seek to overcome this problem by biasing estimates towards solutions that are more likely a priori, typically those with small, smooth, or sparse coefficients. Here we introduce a novel Bayesian receptive field estimator designed to incorporate locality, a powerful form of prior information about receptive field structure. The key to our approach is a hierarchical receptive field model that flexibly adapts to localized structure in both spacetime and spatiotemporal frequency, using an inference method known as empirical Bayes. We refer to our method as automatic locality determination (ALD), and show that it can accurately recover various types of smooth, sparse, and localized receptive fields. We apply ALD to neural data from retinal ganglion cells and V1 simple cells, and find it achieves error rates several times lower than standard estimators. Thus, estimates of comparable accuracy can be achieved with substantially less data. Finally, we introduce a computationally efficient Markov Chain Monte Carlo (MCMC) algorithm for fully Bayesian inference under the ALD prior, yielding accurate Bayesian confidence intervals for small or noisy datasets. PMID- 22046111 TI - Decoding complex chemical mixtures with a physical model of a sensor array. AB - Combinatorial sensor arrays, such as the olfactory system, can detect a large number of analytes using a relatively small number of receptors. However, the complex pattern of receptor responses to even a single analyte, coupled with the non-linearity of responses to mixtures of analytes, makes quantitative prediction of compound concentrations in a mixture a challenging task. Here we develop a physical model that explicitly takes receptor-ligand interactions into account, and apply it to infer concentrations of highly related sugar nucleotides from the output of four engineered G-protein-coupled receptors. We also derive design principles that enable accurate mixture discrimination with cross-specific sensor arrays. The optimal sensor parameters exhibit relatively weak dependence on component concentrations, making a single designed array useful for analyzing a sizable range of mixtures. The maximum number of mixture components that can be successfully discriminated is twice the number of sensors in the array. Finally, antagonistic receptor responses, well-known to play an important role in natural olfactory systems, prove to be essential for the accurate prediction of component concentrations. PMID- 22046112 TI - Conformation regulation of the X chromosome inactivation center: a model. AB - X-Chromosome Inactivation (XCI) is the process whereby one, randomly chosen X becomes transcriptionally silenced in female cells. XCI is governed by the Xic, a locus on the X encompassing an array of genes which interact with each other and with key molecular factors. The mechanism, though, establishing the fate of the X's, and the corresponding alternative modifications of the Xic architecture, is still mysterious. In this study, by use of computer simulations, we explore the scenario where chromatin conformations emerge from its interaction with diffusing molecular factors. Our aim is to understand the physical mechanisms whereby stable, non-random conformations are established on the Xic's, how complex architectural changes are reliably regulated, and how they lead to opposite structures on the two alleles. In particular, comparison against current experimental data indicates that a few key cis-regulatory regions orchestrate the organization of the Xic, and that two major molecular regulators are involved. PMID- 22046113 TI - STDP allows fast rate-modulated coding with Poisson-like spike trains. AB - Spike timing-dependent plasticity (STDP) has been shown to enable single neurons to detect repeatedly presented spatiotemporal spike patterns. This holds even when such patterns are embedded in equally dense random spiking activity, that is, in the absence of external reference times such as a stimulus onset. Here we demonstrate, both analytically and numerically, that STDP can also learn repeating rate-modulated patterns, which have received more experimental evidence, for example, through post-stimulus time histograms (PSTHs). Each input spike train is generated from a rate function using a stochastic sampling mechanism, chosen to be an inhomogeneous Poisson process here. Learning is feasible provided significant covarying rate modulations occur within the typical timescale of STDP (~10-20 ms) for sufficiently many inputs (~100 among 1000 in our simulations), a condition that is met by many experimental PSTHs. Repeated pattern presentations induce spike-time correlations that are captured by STDP. Despite imprecise input spike times and even variable spike counts, a single trained neuron robustly detects the pattern just a few milliseconds after its presentation. Therefore, temporal imprecision and Poisson-like firing variability are not an obstacle to fast temporal coding. STDP provides an appealing mechanism to learn such rate patterns, which, beyond sensory processing, may also be involved in many cognitive tasks. PMID- 22046114 TI - Ten simple rules for getting involved in your scientific community. PMID- 22046116 TI - Teaching bioinformatics at the secondary school level. PMID- 22046115 TI - Grid cells, place cells, and geodesic generalization for spatial reinforcement learning. AB - Reinforcement learning (RL) provides an influential characterization of the brain's mechanisms for learning to make advantageous choices. An important problem, though, is how complex tasks can be represented in a way that enables efficient learning. We consider this problem through the lens of spatial navigation, examining how two of the brain's location representations- hippocampal place cells and entorhinal grid cells--are adapted to serve as basis functions for approximating value over space for RL. Although much previous work has focused on these systems' roles in combining upstream sensory cues to track location, revisiting these representations with a focus on how they support this downstream decision function offers complementary insights into their characteristics. Rather than localization, the key problem in learning is generalization between past and present situations, which may not match perfectly. Accordingly, although neural populations collectively offer a precise representation of position, our simulations of navigational tasks verify the suggestion that RL gains efficiency from the more diffuse tuning of individual neurons, which allows learning about rewards to generalize over longer distances given fewer training experiences. However, work on generalization in RL suggests the underlying representation should respect the environment's layout. In particular, although it is often assumed that neurons track location in Euclidean coordinates (that a place cell's activity declines "as the crow flies" away from its peak), the relevant metric for value is geodesic: the distance along a path, around any obstacles. We formalize this intuition and present simulations showing how Euclidean, but not geodesic, representations can interfere with RL by generalizing inappropriately across barriers. Our proposal that place and grid responses should be modulated by geodesic distances suggests novel predictions about how obstacles should affect spatial firing fields, which provides a new viewpoint on data concerning both spatial codes. PMID- 22046117 TI - Ten simple rules for teaching bioinformatics at the high school level. PMID- 22046118 TI - A first attempt to bring computational biology into advanced high school biology classrooms. AB - Computer science has become ubiquitous in many areas of biological research, yet most high school and even college students are unaware of this. As a result, many college biology majors graduate without adequate computational skills for contemporary fields of biology. The absence of a computational element in secondary school biology classrooms is of growing concern to the computational biology community and biology teachers who would like to acquaint their students with updated approaches in the discipline. We present a first attempt to correct this absence by introducing a computational biology element to teach genetic evolution into advanced biology classes in two local high schools. Our primary goal was to show students how computation is used in biology and why a basic understanding of computation is necessary for research in many fields of biology. This curriculum is intended to be taught by a computational biologist who has worked with a high school advanced biology teacher to adapt the unit for his/her classroom, but a motivated high school teacher comfortable with mathematics and computing may be able to teach this alone. In this paper, we present our curriculum, which takes into consideration the constraints of the required curriculum, and discuss our experiences teaching it. We describe the successes and challenges we encountered while bringing this unit to high school students, discuss how we addressed these challenges, and make suggestions for future versions of this curriculum.We believe that our curriculum can be a valuable seed for further development of computational activities aimed at high school biology students. Further, our experiences may be of value to others teaching computational biology at this level. Our curriculum can be obtained at http://ecsite.cs.colorado.edu/?page_id=149#biology or by contacting the authors. PMID- 22046119 TI - Ten simple rules for developing a short bioinformatics training course. PMID- 22046120 TI - Unbiased simulations reveal the inward-facing conformation of the human serotonin transporter and Na(+) ion release. AB - Monoamine transporters are responsible for termination of synaptic signaling and are involved in depression, control of appetite, and anxiety amongst other neurological processes. Despite extensive efforts, the structures of the monoamine transporters and the transport mechanism of ions and substrates are still largely unknown. Structural knowledge of the human serotonin transporter (hSERT) is much awaited for understanding the mechanistic details of substrate translocation and binding of antidepressants and drugs of abuse. The publication of the crystal structure of the homologous leucine transporter has resulted in homology models of the monoamine transporters. Here we present extended molecular dynamics simulations of an experimentally supported homology model of hSERT with and without the natural substrate yielding a total of more than 1.5 us of simulation of the protein dimer. The simulations reveal a transition of hSERT from an outward-facing occluded conformation to an inward-facing conformation in a one-substrate-bound state. Simulations with a second substrate in the proposed symport effector site did not lead to conformational changes associated with translocation. The central substrate binding site becomes fully exposed to the cytoplasm leaving both the Na(+)-ion in the Na2-site and the substrate in direct contact with the cytoplasm through water interactions. The simulations reveal how sodium is released and show indications of early events of substrate transport. The notion that ion dissociation from the Na2-site drives translocation is supported by experimental studies of a Na2-site mutant. Transmembrane helices (TMs) 1 and 6 are identified as the helices involved in the largest movements during transport. PMID- 22046121 TI - LTS and FS inhibitory interneurons, short-term synaptic plasticity, and cortical circuit dynamics. AB - Somatostatin-expressing, low threshold-spiking (LTS) cells and fast-spiking (FS) cells are two common subtypes of inhibitory neocortical interneuron. Excitatory synapses from regular-spiking (RS) pyramidal neurons to LTS cells strongly facilitate when activated repetitively, whereas RS-to-FS synapses depress. This suggests that LTS neurons may be especially relevant at high rate regimes and protect cortical circuits against over-excitation and seizures. However, the inhibitory synapses from LTS cells usually depress, which may reduce their effectiveness at high rates. We ask: by which mechanisms and at what firing rates do LTS neurons control the activity of cortical circuits responding to thalamic input, and how is control by LTS neurons different from that of FS neurons? We study rate models of circuits that include RS cells and LTS and FS inhibitory cells with short-term synaptic plasticity. LTS neurons shift the RS firing-rate vs. current curve to the right at high rates and reduce its slope at low rates; the LTS effect is delayed and prolonged. FS neurons always shift the curve to the right and affect RS firing transiently. In an RS-LTS-FS network, FS neurons reach a quiescent state if they receive weak input, LTS neurons are quiescent if RS neurons receive weak input, and both FS and RS populations are active if they both receive large inputs. In general, FS neurons tend to follow the spiking of RS neurons much more closely than LTS neurons. A novel type of facilitation induced slow oscillations is observed above the LTS firing threshold with a frequency determined by the time scale of recovery from facilitation. To conclude, contrary to earlier proposals, LTS neurons affect the transient and steady state responses of cortical circuits over a range of firing rates, not only during the high rate regime; LTS neurons protect against over-activation about as well as FS neurons. PMID- 22046122 TI - Second order dimensionality reduction using minimum and maximum mutual information models. AB - Conventional methods used to characterize multidimensional neural feature selectivity, such as spike-triggered covariance (STC) or maximally informative dimensions (MID), are limited to Gaussian stimuli or are only able to identify a small number of features due to the curse of dimensionality. To overcome these issues, we propose two new dimensionality reduction methods that use minimum and maximum information models. These methods are information theoretic extensions of STC that can be used with non-Gaussian stimulus distributions to find relevant linear subspaces of arbitrary dimensionality. We compare these new methods to the conventional methods in two ways: with biologically-inspired simulated neurons responding to natural images and with recordings from macaque retinal and thalamic cells responding to naturalistic time-varying stimuli. With non-Gaussian stimuli, the minimum and maximum information methods significantly outperform STC in all cases, whereas MID performs best in the regime of low dimensional feature spaces. PMID- 22046123 TI - A sparse coding model with synaptically local plasticity and spiking neurons can account for the diverse shapes of V1 simple cell receptive fields. AB - Sparse coding algorithms trained on natural images can accurately predict the features that excite visual cortical neurons, but it is not known whether such codes can be learned using biologically realistic plasticity rules. We have developed a biophysically motivated spiking network, relying solely on synaptically local information, that can predict the full diversity of V1 simple cell receptive field shapes when trained on natural images. This represents the first demonstration that sparse coding principles, operating within the constraints imposed by cortical architecture, can successfully reproduce these receptive fields. We further prove, mathematically, that sparseness and decorrelation are the key ingredients that allow for synaptically local plasticity rules to optimize a cooperative, linear generative image model formed by the neural representation. Finally, we discuss several interesting emergent properties of our network, with the intent of bridging the gap between theoretical and experimental studies of visual cortex. PMID- 22046124 TI - Metabolic regulation in progression to autoimmune diabetes. AB - Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede beta-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes. PMID- 22046125 TI - Quorum sensing in fungi: Q&A. PMID- 22046126 TI - Frequent and recent human acquisition of simian foamy viruses through apes' bites in central Africa. AB - Human infection by simian foamy viruses (SFV) can be acquired by persons occupationally exposed to non-human primates (NHP) or in natural settings. This study aimed at getting better knowledge on SFV transmission dynamics, risk factors for such a zoonotic infection and, searching for intra-familial dissemination and the level of peripheral blood (pro)viral loads in infected individuals. We studied 1,321 people from the general adult population (mean age 49 yrs, 640 women and 681 men) and 198 individuals, mostly men, all of whom had encountered a NHP with a resulting bite or scratch. All of these, either Pygmies (436) or Bantus (1085) live in villages in South Cameroon. A specific SFV Western blot was used and two nested PCRs (polymerase, and LTR) were done on all the positive/borderline samples by serology. In the general population, 2/1,321 (0.2%) persons were found to be infected. In the second group, 37/198 (18.6%) persons were SFV positive. They were mostly infected by apes (37/39) FV (mainly gorilla). Infection by monkey FV was less frequent (2/39). The viral origin of the amplified sequences matched with the history reported by the hunters, most of which (83%) are aged 20 to 40 years and acquired the infection during the last twenty years. The (pro)viral load in 33 individuals infected by a gorilla FV was quite low (<1 to 145 copies per 10(5) cells) in the peripheral blood leucocytes. Of the 30 wives and 12 children from families of FV infected persons, only one woman was seropositive in WB without subsequent viral DNA amplification. We demonstrate a high level of recent transmission of SFVs to humans in natural settings specifically following severe gorilla bites during hunting activities. The virus was found to persist over several years, with low SFV loads in infected persons. Secondary transmission remains an open question. PMID- 22046127 TI - Non-hematopoietic cells in lymph nodes drive memory CD8 T cell inflation during murine cytomegalovirus infection. AB - During human and murine cytomegalovirus (MCMV) infection an exceptionally large virus-specific CD8 T cell pool is maintained in the periphery lifelong. This anomalous response is only seen for specific subsets of MCMV-specific CD8 T cells which are referred to as 'inflationary T cells'. How memory CD8 T cell inflation is induced and maintained is unclear, though their activated phenotype strongly suggests an involvement of persistent antigen encounter during MCMV latency. To dissect the cellular and molecular requirements for memory CD8 T cell inflation, we have generated a transgenic mouse expressing an MHC class I-restricted T cell receptor specific for an immunodominant inflationary epitope of MCMV. Through a series of adoptive transfer experiments we found that memory inflation was completely dependent on antigen presentation by non-hematopoietic cells, which are also the predominant site of MCMV latency. In particular, non-hematopoietic cells selectively induced robust proliferation of inflationary CD8 T cells in lymph nodes, where a majority of the inflationary CD8 T cells exhibit a central memory phenotype, but not in peripheral tissues, where terminally differentiated inflationary T cells accumulate. These results indicate that continuous restimulation of central memory CD8 T cells in the lymph nodes by infected non hematopoietic cells ensures the maintenance of a functional effector CD8 T pool in the periphery, providing protection against viral reactivation events. PMID- 22046128 TI - Deep molecular characterization of HIV-1 dynamics under suppressive HAART. AB - In order to design strategies for eradication of HIV-1 from infected individuals, detailed insight into the HIV-1 reservoirs that persist in patients on suppressive antiretroviral therapy (ART) is required. In this regard, most studies have focused on integrated (proviral) HIV-1 DNA forms in cells circulating in blood. However, the majority of proviral DNA is replication defective and archival, and as such, has limited ability to reveal the dynamics of the viral population that persists in patients on suppressive ART. In contrast, extrachromosomal (episomal) viral DNA is labile and as a consequence is a better surrogate for recent infection events and is able to inform on the extent to which residual replication contributes to viral reservoir maintenance. To gain insight into the diversity and compartmentalization of HIV-1 under suppressive ART, we extensively analyzed longitudinal peripheral blood mononuclear cells (PBMC) samples by deep sequencing of episomal and integrated HIV-1 DNA from patients undergoing raltegravir intensification. Reverse transcriptase genes selectively amplified from episomal and proviral HIV-1 DNA were analyzed by deep sequencing 0, 2, 4, 12, 24 and 48 weeks after raltegravir intensification. We used maximum likelihood phylogenies and statistical tests (AMOVA and Slatkin-Maddison (SM)) in order to determine molecular compartmentalization. We observed low molecular variance (mean variability <=0.042). Although phylogenies showed that both DNA forms were intermingled within the phylogenetic tree, we found a statistically significant compartmentalization between episomal and proviral DNA samples (P<10(-6) AMOVA test; P = 0.001 SM test), suggesting that they belong to different viral populations. In addition, longitudinal analysis of episomal and proviral DNA by phylogeny and AMOVA showed signs of non-chronological temporal compartmentalization (all comparisons P<10(-6)) suggesting that episomal and proviral DNA forms originated from different anatomical compartments. Collectively, this suggests the presence of a chronic viral reservoir in which there is stochastic release of infectious virus and in which there are limited rounds of de novo infection. This could be explained by the existence of different reservoirs with unique pharmacological accessibility properties, which will require strategies that improve drug penetration/retention within these reservoirs in order to minimise maintenance of the viral reservoir by de novo infection. PMID- 22046129 TI - Histone deacetylase 8 is required for centrosome cohesion and influenza A virus entry. AB - Influenza A virus (IAV) enters host cells by endocytosis followed by acid activated penetration from late endosomes (LEs). Using siRNA silencing, we found that histone deacetylase 8 (HDAC8), a cytoplasmic enzyme, efficiently promoted productive entry of IAV into tissue culture cells, whereas HDAC1 suppressed it. HDAC8 enhanced endocytosis, acidification, and penetration of the incoming virus. In contrast, HDAC1 inhibited acidification and penetration. The effects were connected with dramatic alterations in the organization of the microtubule system, and, as a consequence, a change in the behavior of LEs and lysosomes (LYs). Depletion of HDAC8 caused loss of centrosome-associated microtubules and loss of directed centripetal movement of LEs, dispersing LE/LYs to the cell periphery. For HDAC1, the picture was the opposite. To explain these changes, centrosome cohesion emerged as the critical factor. Depletion of HDAC8 caused centrosome splitting, which could also be induced by depleting a centriole-linker protein, rootletin. In both cases, IAV infection was inhibited. HDAC1 depletion reduced the splitting of centrosomes, and enhanced infection. The longer the distance between centrosomes, the lower the level of infection. HDAC8 depletion was also found to inhibit infection of Uukuniemi virus (a bunyavirus) suggesting common requirements among late penetrating enveloped viruses. The results established class I HDACs as powerful regulators of microtubule organization, centrosome function, endosome maturation, and infection by IAV and other late penetrating viruses. PMID- 22046130 TI - Leishmania mitochondrial peroxiredoxin plays a crucial peroxidase-unrelated role during infection: insight into its novel chaperone activity. AB - Two-cysteine peroxiredoxins are ubiquitous peroxidases that play various functions in cells. In Leishmania and related trypanosomatids, which lack catalase and selenium-glutathione peroxidases, the discovery of this family of enzymes provided the molecular basis for peroxide removal in these organisms. In this report the functional relevance of one of such enzymes, the mitochondrial 2 Cys peroxiredoxin (mTXNPx), was investigated along the Leishmania infantum life cycle. mTXNPx null mutants (mtxnpx(-)) produced by a gene replacement strategy, while indistinguishable from wild type promastigotes, were found unable to thrive in a murine model of infection. Unexpectedly, however, the avirulent phenotype of mtxnpx(-) was not due to lack of the peroxidase activity of mTXNPx as these behaved like controls when exposed to oxidants added exogenously or generated by macrophages during phagocytosis ex vivo. In line with this, mtxnpx(-) were also avirulent when inoculated into murine hosts unable to mount an effective oxidative phagocyte response (B6.p47(phox-/-) and B6.RAG2(-/-) IFN-gamma(-/-) mice). Definitive conclusion that the peroxidase activity of mTXNPx is not required for parasite survival in mice was obtained by showing that a peroxidase inactive version of this protein was competent in rescuing the non-infective phenotype of mtxnpx(-). A novel function is thus proposed for mTXNPx, that of a molecular chaperone, which may explain the impaired infectivity of the null mutants. This premise is based on the observation that the enzyme is able to suppress the thermal aggregation of citrate synthase in vitro. Also, mtxnpx(-) were more sensitive than controls to a temperature shift from 25 degrees C to 37 degrees C, a phenotype reminiscent of organisms lacking specific chaperone genes. Collectively, the findings reported here change the paradigm which regards all trypanosomatid 2-Cys peroxiredoxins as peroxide-eliminating devices. Moreover, they demonstrate, for the first time, that these 2-Cys peroxiredoxins can be determinant for pathogenicity independently of their peroxidase activity. PMID- 22046131 TI - Tubule-guided cell-to-cell movement of a plant virus requires class XI myosin motors. AB - Cell-to-cell movement of plant viruses occurs via plasmodesmata (PD), organelles that evolved to facilitate intercellular communications. Viral movement proteins (MP) modify PD to allow passage of the virus particles or nucleoproteins. This passage occurs via several distinct mechanisms one of which is MP-dependent formation of the tubules that traverse PD and provide a conduit for virion translocation. The MP of tubule-forming viruses including Grapevine fanleaf virus (GFLV) recruit the plant PD receptors called Plasmodesmata Located Proteins (PDLP) to mediate tubule assembly and virus movement. Here we show that PDLP1 is transported to PD through a specific route within the secretory pathway in a myosin-dependent manner. This transport relies primarily on the class XI myosins XI-K and XI-2. Inactivation of these myosins using dominant negative inhibition results in mislocalization of PDLP and MP and suppression of GFLV movement. We also found that the proper targeting of specific markers of the Golgi apparatus, the plasma membrane, PD, lipid raft subdomains within the plasma membrane, and the tonoplast was not affected by myosin XI-K inhibition. However, the normal tonoplast dynamics required myosin XI-K activity. These results reveal a new pathway of the myosin-dependent protein trafficking to PD that is hijacked by GFLV to promote tubule-guided transport of this virus between plant cells. PMID- 22046132 TI - The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors. AB - Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock. PMID- 22046133 TI - Herpesvirus telomerase RNA (vTR) with a mutated template sequence abrogates herpesvirus-induced lymphomagenesis. AB - Telomerase reverse transcriptase (TERT) and telomerase RNA (TR) represent the enzymatically active components of telomerase. In the complex, TR provides the template for the addition of telomeric repeats to telomeres, a protective structure at the end of linear chromosomes. Human TR with a mutation in the template region has been previously shown to inhibit proliferation of cancer cells in vitro. In this report, we examined the effects of a mutation in the template of a virus encoded TR (vTR) on herpesvirus-induced tumorigenesis in vivo. For this purpose, we used the oncogenic avian herpesvirus Marek's disease virus (MDV) as a natural virus-host model for lymphomagenesis. We generated recombinant MDV in which the vTR template sequence was mutated from AATCCCAATC to ATATATATAT (vAU5) by two-step Red-mediated mutagenesis. Recombinant viruses harboring the template mutation replicated with kinetics comparable to parental and revertant viruses in vitro. However, mutation of the vTR template sequence completely abrogated virus-induced tumor formation in vivo, although the virus was able to undergo low-level lytic replication. To confirm that the absence of tumors was dependent on the presence of mutant vTR in the telomerase complex, a second mutation was introduced in vAU5 that targeted the P6.1 stem loop, a conserved region essential for vTR-TERT interaction. Absence of vTR-AU5 from the telomerase complex restored virus-induced lymphoma formation. To test if the attenuated vAU5 could be used as an effective vaccine against MDV, we performed vaccination-challenge studies and determined that vaccination with vAU5 completely protected chickens from lethal challenge with highly virulent MDV. Taken together, our results demonstrate 1) that mutation of the vTR template sequence can completely abrogate virus-induced tumorigenesis, likely by the inhibition of cancer cell proliferation, and 2) that this strategy could be used to generate novel vaccine candidates against virus-induced lymphoma. PMID- 22046134 TI - RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus. AB - Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2 activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions. PMID- 22046135 TI - IFITM3 inhibits influenza A virus infection by preventing cytosolic entry. AB - To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats. PMID- 22046136 TI - Coordinated destruction of cellular messages in translation complexes by the gammaherpesvirus host shutoff factor and the mammalian exonuclease Xrn1. AB - Several viruses encode factors that promote host mRNA degradation to silence gene expression. It is unclear, however, whether cellular mRNA turnover pathways are engaged to assist in this process. In Kaposi's sarcoma-associated herpesvirus this phenotype is enacted by the host shutoff factor SOX. Here we show that SOX induced mRNA turnover is a two-step process, in which mRNAs are first cleaved internally by SOX itself then degraded by the cellular exonuclease Xrn1. SOX therefore bypasses the regulatory steps of deadenylation and decapping normally required for Xrn1 activation. SOX is likely recruited to translating mRNAs, as it cosediments with translation initiation complexes and depletes polysomes. Cleaved mRNA intermediates accumulate in the 40S fraction, indicating that recognition occurs at an early stage of translation. This is the first example of a viral protein commandeering cellular mRNA turnover pathways to destroy host mRNAs, and suggests that Xrn1 is poised to deplete messages undergoing translation in mammalian cells. PMID- 22046137 TI - Targeting cattle-borne zoonoses and cattle pathogens using a novel trypanosomatid based delivery system. AB - Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis. PMID- 22046138 TI - Signal transduction through CsrRS confers an invasive phenotype in group A Streptococcus. AB - The CsrRS (or CovRS) two component system controls expression of up to 15% of the genome of group A Streptococcus (GAS). While some studies have suggested that the sensor histidine kinase CsrS responds to membrane perturbations as a result of various environmental stresses, other data have implicated the human antimicrobial peptide LL-37 and extracellular Mg(2+) as specific signals. We now report that Mg(2+) and LL-37 have opposite effects on expression of multiple genes that are activated or repressed by the transcriptional regulator CsrR. Using a GAS isolate representative of the recently emerged and widely disseminated M1T1 clone implicated in severe invasive disease, we found marked up regulation by CsrRS of multiple virulence factors including pyrogenic exotoxin A, DNase Sda1, streptolysin O, and the hyaluronic acid capsular polysaccharide, among others. Topology and surface protein labeling studies indicated that CsrS is associated with the bacterial cell membrane and has a surface-exposed extracellular domain accessible to environmental ligands. Replacement of a cluster of three acidic amino acids with uncharged residues in the extracellular domain of CsrS abrogated LL-37 signaling and conferred a hyporesponsive phenotype consistent with tonic activation of CsrS autokinase activity, an effect that could be overridden by mutation of the CsrS active site histidine. Both loss- and gain-of-function mutations of a conserved site in the receiver domain of CsrR established an essential role for lysine 102 in CsrS-to-CsrR signal transduction. These results provide strong evidence that Mg(2+) and LL-37 are specific signals that function by altering CsrS autokinase activity and downstream phosphotransfer to CsrR to modulate its activity as a transcriptional regulator. The representation of multiple antiphagocytic and cytotoxic factors in the CsrRS regulon together with results of in vitro phagocytic killing assays support the hypothesis that CsrRS mediates conversion of GAS from a colonizing to an invasive phenotype in response to signaling by host LL-37. PMID- 22046139 TI - Insights into Hox protein function from a large scale combinatorial analysis of protein domains. AB - Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox controlled developmental programs. Importantly, the results highlight context dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences. PMID- 22046140 TI - Role of exonic variation in chemokine receptor genes on AIDS: CCRL2 F167Y association with pneumocystis pneumonia. AB - Chromosome 3p21-22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naive HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2 associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP) (RH = 2.84, 95% CI 1.28-6.31) among four major AIDS-defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation. PMID- 22046141 TI - Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a complex trait characterised by the production of a range of auto-antibodies and a diverse set of clinical phenotypes. Currently, ~8% of the genetic contribution to SLE in Europeans is known, following publication of several moderate-sized genome-wide (GW) association studies, which identified loci with a strong effect (OR>1.3). In order to identify additional genes contributing to SLE susceptibility, we conducted a replication study in a UK dataset (870 cases, 5,551 controls) of 23 variants that showed moderate-risk for lupus in previous studies. Association analysis in the UK dataset and subsequent meta-analysis with the published data identified five SLE susceptibility genes reaching genome-wide levels of significance (P(comb)<5*10(-8)): NCF2 (P(comb) = 2.87*10(-11)), IKZF1 (P(comb) = 2.33*10(-9)), IRF8 (P(comb) = 1.24*10(-8)), IFIH1 (P(comb) = 1.63*10(-8)), and TYK2 (P(comb) = 3.88*10(-8)). Each of the five new loci identified here can be mapped into interferon signalling pathways, which are known to play a key role in the pathogenesis of SLE. These results increase the number of established susceptibility genes for lupus to ~30 and validate the importance of using large datasets to confirm associations of loci which moderately increase the risk for disease. PMID- 22046142 TI - Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis. AB - Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic species of Onygenales to transfer from soil to animal hosts. PMID- 22046143 TI - A conserved developmental patterning network produces quantitatively different output in multiple species of Drosophila. AB - Differences in the level, timing, or location of gene expression can contribute to alternative phenotypes at the molecular and organismal level. Understanding the origins of expression differences is complicated by the fact that organismal morphology and gene regulatory networks could potentially vary even between closely related species. To assess the scope of such changes, we used high resolution imaging methods to measure mRNA expression in blastoderm embryos of Drosophila yakuba and Drosophila pseudoobscura and assembled these data into cellular resolution atlases, where expression levels for 13 genes in the segmentation network are averaged into species-specific, cellular resolution morphological frameworks. We demonstrate that the blastoderm embryos of these species differ in their morphology in terms of size, shape, and number of nuclei. We present an approach to compare cellular gene expression patterns between species, while accounting for varying embryo morphology, and apply it to our data and an equivalent dataset for Drosophila melanogaster. Our analysis reveals that all individual genes differ quantitatively in their spatio-temporal expression patterns between these species, primarily in terms of their relative position and dynamics. Despite many small quantitative differences, cellular gene expression profiles for the whole set of genes examined are largely similar. This suggests that cell types at this stage of development are conserved, though they can differ in their relative position by up to 3-4 cell widths and in their relative proportion between species by as much as 5-fold. Quantitative differences in the dynamics and relative level of a subset of genes between corresponding cell types may reflect altered regulatory functions between species. Our results emphasize that transcriptional networks can diverge over short evolutionary timescales and that even small changes can lead to distinct output in terms of the placement and number of equivalent cells. PMID- 22046144 TI - Small RNAs prevent transcription-coupled loss of histone H3 lysine 9 methylation in Arabidopsis thaliana. AB - In eukaryotes, histone H3 lysine 9 methylation (H3K9me) mediates silencing of invasive sequences to prevent deleterious consequences including the expression of aberrant gene products and mobilization of transposons. In Arabidopsis thaliana, H3K9me maintained by SUVH histone methyltransferases (MTases) is associated with cytosine methylation (5meC) maintained by the CMT3 cytosine MTase. The SUVHs contain a 5meC binding domain and CMT3 contains an H3K9me binding domain, suggesting that the SUVH/CMT3 pathway involves an amplification loop between H3K9me and 5meC. However, at loci subject to read-through transcription, the stability of the H3K9me/5meC loop requires a mechanism to counteract transcription-coupled loss of H3K9me. Here we use the duplicated PAI genes, which stably maintain SUVH-dependent H3K9me and CMT3-dependent 5meC despite read-through transcription, to show that when PAI sRNAs are depleted by dicer ribonuclease mutations, PAI H3K9me and 5meC levels are reduced and remaining PAI 5meC is destabilized upon inbreeding. The dicer mutations confer weaker reductions in PAI 5meC levels but similar or stronger reductions in PAI H3K9me levels compared to a cmt3 mutation. This comparison indicates a connection between sRNAs and maintenance of H3K9me independent of CMT3 function. The dicer mutations reduce PAI H3K9me and 5meC levels through a distinct mechanism from the known role of dicer-dependent sRNAs in guiding the DRM2 cytosine MTase because the PAI genes maintain H3K9me and 5meC at levels similar to wild type in a drm2 mutant. Our results support a new role for sRNAs in plants to prevent transcription-coupled loss of H3K9me. PMID- 22046145 TI - Antioxidant Activities of Plumbagin and Its Cu (II) Complex. AB - Plumbagin and its Cu (II) complex [Cu (plumbagin)(2)].H(2)O have been synthesized, and their antioxidant activities towards the inhibitory effect on DPPH free radical, reducing power, total antioxidant capacity, and inhibition on lipid peroxidation were investigated. Plumbagin and its Cu (II) complex were found to exhibit scavenging activities on DPPH radical with the inhibitory rate of 41% and 24%, respectively. The reducing power of plumbagin was outstanding at the concentrations of 1.0, 1.5, and 2.0 mg/mL, compared to Cu (II) complex and synthetic antioxidant 2,6-di-ter-butyl-4-methylphenol (BHT); the highest level reached 1.333 for plumbagin and 0.581 for Cu (II) complex. Also, the inhibition on lipid peroxidation of plumbagin was higher than that of Cu (II) complex and BHT, 46.4% for plumbagin and 24.5% for Cu (II) complex. The results give a strong impact for designing anticancer drugs, combined with their potential cytotoxic and antioxidant activities, which can be targeted selectively against cancer cells and increase their therapeutic index and additional advantages over other anticancer drugs. PMID- 22046146 TI - Dietary quality may enhance survival related to cognitive impairment in Taiwanese elderly. AB - BACKGROUND: Impaired cognition increases mortality in the aged. It is unclear how dietary quality might affect this relationship. OBJECTIVE: To examine how dietary diversity and cognition might interact to determine survival. DESIGN: In a Nutrition and Health Survey in Taiwan (NAHSIT 1999-2000), 1,839 representative elderly were followed for mortality up to 10 years. The dietary quality measure was a dietary diversity score (DDS, range: 0-6) to present six food groups (dairy, meat, rice and grains, fruit, vegetable,fat and oil) derived from a 24-h dietary recall. Cognitive function was evaluated by the validated Short Portable Mental Status Questionnaire (SPMSQ). RESULTS: Those with cognitive impairment (SPMSQ>=3 errors) had 2.56 (95% confidence intervals (CI), 1.99-3.28) times the all-cause-mortality risk of those with intact cognition. After control for potential confounders, the adjusted hazard ratio (HR) remained significant (1.46, 95% CI: 1.06-2.02). Significant interactions for DDS and cognition were found (p<0.001). Jointly, compared to normal-SPMSQ-highest DDS, the greatest HR is where impaired cognition is combined with the lowest DDS (HR 2.24, 95% CI: 1.19 4.24). Increased DDS was associated with improvement in survival that is especially evident in those with 1-2 errors where the greatest HR reduction was found, and for fruit. Attributability for mortality amounted to 18% for impaired cognition and 33% for least diverse diet. CONCLUSIONS: Dietary diversity may improve survival in relation to impaired cognitive function. PMID- 22046147 TI - Molecular Assembly and Biosynthesis of Acetylcholinesterase in Brain and Muscle: the Roles of t-peptide, FHB Domain, and N-linked Glycosylation. AB - Acetylcholinesterase (AChE) is responsible for the hydrolysis of the neurotransmitter, acetylcholine, in the nervous system. The functional localization and oligomerization of AChE T variant are depending primarily on the association of their anchoring partners, either collagen tail (ColQ) or proline rich membrane anchor (PRiMA). Complexes with ColQ represent the asymmetric forms (A(12)) in muscle, while complexes with PRiMA represent tetrameric globular forms (G(4)) mainly found in brain and muscle. Apart from these traditional molecular forms, a ColQ-linked asymmetric form and a PRiMA-linked globular form of hybrid cholinesterases (ChEs), having both AChE and BChE catalytic subunits, were revealed in chicken brain and muscle. The similarity of various molecular forms of AChE and BChE raises interesting question regarding to their possible relationship in enzyme assembly and localization. The focus of this review is to provide current findings about the biosynthesis of different forms of ChEs together with their anchoring proteins. PMID- 22046148 TI - Signaling mechanisms in cortical axon growth, guidance, and branching. AB - Precise wiring of cortical circuits during development depends upon axon extension, guidance, and branching to appropriate targets. Motile growth cones at axon tips navigate through the nervous system by responding to molecular cues, which modulate signaling pathways within axonal growth cones. Intracellular calcium signaling has emerged as a major transducer of guidance cues but exactly how calcium signaling pathways modify the actin and microtubule cytoskeleton to evoke growth cone behaviors and axon branching is still mysterious. Axons must often pause their extension in tracts while their branches extend into targets. Some evidence suggests a competition between growth of axons and branches but the mechanisms are poorly understood. Since it is difficult to study growing axons deep within the mammalian brain, much of what we know about signaling pathways and cytoskeletal dynamics of growth cones comes from tissue culture studies, in many cases, of non-mammalian species. Consequently it is not well understood how guidance cues relevant to mammalian neural development in vivo signal to the growth cone cytoskeleton during axon outgrowth and guidance. In this review we describe our recent work in dissociated cultures of developing rodent sensorimotor cortex in the context of the current literature on molecular guidance cues, calcium signaling pathways, and cytoskeletal dynamics that regulate growth cone behaviors. A major challenge is to relate findings in tissue culture to mechanisms of cortical development in vivo. Toward this goal, we describe our recent work in cortical slices, which preserve the complex cellular and molecular environment of the mammalian brain but allow direct visualization of growth cone behaviors and calcium signaling. Findings from this work suggest that mechanisms regulating axon growth and guidance in dissociated culture neurons also underlie development of cortical connectivity in vivo. PMID- 22046149 TI - Effects of accuracy feedback on fractal characteristics of time estimation. AB - The current experiment investigated the effect of visual accuracy feedback on the structure of variability of time interval estimates in the continuation tapping paradigm. Participants were asked to repeatedly estimate a 1-s interval for a prolonged period of time by tapping their index finger. In some conditions, participants received accuracy feedback after every estimate, whereas in other conditions, no feedback was given. Also, the likelihood of receiving visual feedback was manipulated by adjusting the tolerance band around the 1-s target interval so that feedback was displayed only if the temporal estimate deviated from the target interval by more than 50, 100, or 200 ms respectively. We analyzed the structure of variability of the inter-tap intervals with fractal and multifractal methods that allow for a quantification of complex long-range correlation patterns in the timing performance. Our results indicate that feedback changes the long-range correlation structure of time estimates: Increased amounts of feedback lead to a decrease in fractal long-range correlations, as well to a decrease in the magnitude of local fluctuations in the performance. The multifractal characteristics of the time estimates were not impacted by the presence of accuracy feedback. Nevertheless, most of the data sets show significant multifractal signatures. We interpret these findings as showing that feedback acts to constrain and possibly reorganize timing performance. Implications for mechanistic and complex systems-based theories of timing behavior are discussed. PMID- 22046150 TI - Dopamine Modulates Striato-Frontal Functioning during Temporal Processing. PMID- 22046151 TI - Acute effects of delta-9-tetrahydrocannabinol on performance monitoring in healthy volunteers. AB - RATIONALE: The error-related negativity (ERN) is a negative event-related potential that occurs immediately after an erroneous response and is thought to reflect human performance monitoring. Delta-9-Tetrahydrocannabinol (THC) administration in healthy volunteers has been linked to impaired performance monitoring in behavioral studies, but to date no studies have examined the effects of cannabinoids on the ERN. METHODS: EEG data from 10 healthy volunteers was recorded during execution of a speeded choice-reaction-time task (Flankers task) after administration of THC or placebo vapor in a double-blind randomized crossover design. RESULTS: The findings of this study show that the ERN was significantly reduced after administration of THC. The behavioral outcomes on the Flankers task showed no indications of drug-induced impairments. DISCUSSION: The diminished ERN reflects impairments in the process of performance monitoring. The task design was not optimized to find behavioral effects. The study shows that cannabinoids impair performance monitoring. PMID- 22046152 TI - Speech production as state feedback control. AB - Spoken language exists because of a remarkable neural process. Inside a speaker's brain, an intended message gives rise to neural signals activating the muscles of the vocal tract. The process is remarkable because these muscles are activated in just the right way that the vocal tract produces sounds a listener understands as the intended message. What is the best approach to understanding the neural substrate of this crucial motor control process? One of the key recent modeling developments in neuroscience has been the use of state feedback control (SFC) theory to explain the role of the CNS in motor control. SFC postulates that the CNS controls motor output by (1) estimating the current dynamic state of the thing (e.g., arm) being controlled, and (2) generating controls based on this estimated state. SFC has successfully predicted a great range of non-speech motor phenomena, but as yet has not received attention in the speech motor control community. Here, we review some of the key characteristics of speech motor control and what they say about the role of the CNS in the process. We then discuss prior efforts to model the role of CNS in speech motor control, and argue that these models have inherent limitations - limitations that are overcome by an SFC model of speech motor control which we describe. We conclude by discussing a plausible neural substrate of our model. PMID- 22046154 TI - The Pupil Reflects Motor Preparation for Saccades - Even before the Eye Starts to Move. AB - The eye produces saccadic eye movements whose reaction times are perhaps the shortest in humans. Saccade latencies reflect ongoing cortical processing and, generally, shorter latencies are supposed to reflect advanced motor preparation. The dilation of the eye's pupil is reported to reflect cortical processing as well. Eight participants made saccades in a gap and overlap paradigm (in pure and mixed blocks), which we used in order to produce a variety of different saccade latencies. Saccades and pupil size were measured with the EyeLink II. The pattern in pupil dilation resembled that of a gap effect: for gap blocks, pupil dilations were larger compared to overlap blocks; mixing gap and overlap trials reduced the pupil dilation for gap trials thereby inducing a switching cost. Furthermore, saccade latencies across all tasks predicted the magnitude of pupil dilations post hoc: the longer the saccade latency the smaller the pupil dilation before the eye actually began to move. In accordance with observations for manual responses, we conclude that pupil dilations prior to saccade execution reflect advanced motor preparations and therefore provide valid indicator qualities for ongoing cortical processes. PMID- 22046153 TI - Neural correlates of visual-spatial attention in electrocorticographic signals in humans. AB - Attention is a cognitive selection mechanism that allocates the limited processing resources of the brain to the sensory streams most relevant to our immediate goals, thereby enhancing responsiveness and behavioral performance. The underlying neural mechanisms of orienting attention are distributed across a widespread cortical network. While aspects of this network have been extensively studied, details about the electrophysiological dynamics of this network are scarce. In this study, we investigated attentional networks using electrocorticographic (ECoG) recordings from the surface of the brain, which combine broad spatial coverage with high temporal resolution, in five human subjects. ECoG was recorded when subjects covertly attended to a spatial location and responded to contrast changes in the presence of distractors in a modified Posner cueing task. ECoG amplitudes in the alpha, beta, and gamma bands identified neural changes associated with covert attention and motor preparation/execution in the different stages of the task. The results show that attentional engagement was primarily associated with ECoG activity in the visual, prefrontal, premotor, and parietal cortices. Motor preparation/execution was associated with ECoG activity in premotor/sensorimotor cortices. In summary, our results illustrate rich and distributed cortical dynamics that are associated with orienting attention and the subsequent motor preparation and execution. These findings are largely consistent with and expand on primate studies using intracortical recordings and human functional neuroimaging studies. PMID- 22046155 TI - Social misdirection fails to enhance a magic illusion. AB - Visual, multisensory and cognitive illusions in magic performances provide new windows into the psychological and neural principles of perception, attention, and cognition. We investigated a magic effect consisting of a coin "vanish" (i.e., the perceptual disappearance of a coin after a simulated toss from hand to hand). Previous research has shown that magicians can use joint attention cues such as their own gaze direction to strengthen the observers' perception of magic. Here we presented naive observers with videos including real and simulated coin tosses to determine if joint attention might enhance the illusory perception of simulated coin tosses. The observers' eye positions were measured, and their perceptual responses simultaneously recorded via button press. To control for the magician's use of joint attention cues, we occluded his head in half of the trials. We found that subjects did not direct their gaze at the magician's face at the time of the coin toss, whether the face was visible or occluded, and that the presence of the magician's face did not enhance the illusion. Thus, our results show that joint attention is not necessary for the perception of this effect. We conclude that social misdirection is redundant and possibly detracting to this very robust sleight-of-hand illusion. We further determined that subjects required multiple trials to effectively distinguish real from simulated tosses; thus the illusion was resilient to repeated viewing. PMID- 22046156 TI - Attentional modulation of binocular rivalry. AB - Ever since Wheatstone initiated the scientific study of binocular rivalry, it has been debated whether the phenomenon is under attentional control. In recent years, the issue of attentional modulation of binocular rivalry has seen a revival. Here we review the classical studies as well as recent advances in the study of attentional modulation of binocular rivalry. We show that (1) voluntary control over binocular rivalry is possible, yet limited, (2) both endogenous and exogenous attention influence perceptual dominance during rivalry, (3) diverting attention from rival displays does not arrest perceptual alternations, and that (4) rival targets by themselves can also attract attention. From a theoretical perspective, we suggest that attention affects binocular rivalry by modulating the effective contrast of the images in competition. This contrast enhancing effect of top-down attention is counteracted by a response attenuating effect of neural adaptation at early levels of visual processing, which weakens the response to the dominant image. Moreover, we conclude that although frontal and parietal brain areas involved in both binocular rivalry and visual attention overlap, an adapting reciprocal inhibition arrangement at early visual cortex is sufficient to trigger switches in perceptual dominance independently of a higher level "selection" mechanisms. Both of these processes are reciprocal and therefore self-balancing, with the consequence that complete attentional control over binocular rivalry can never be realized. PMID- 22046157 TI - Music and the Auditory Brain: Where is the Connection? AB - Sound processing by the auditory system is understood in unprecedented details, even compared with sensory coding in the visual system. Nevertheless, we do not understand yet the way in which some of the simplest perceptual properties of sounds are coded in neuronal activity. This poses serious difficulties for linking neuronal responses in the auditory system and music processing, since music operates on abstract representations of sounds. Paradoxically, although perceptual representations of sounds most probably occur high in auditory system or even beyond it, neuronal responses are strongly affected by the temporal organization of sound streams even in subcortical stations. Thus, to the extent that music is organized sound, it is the organization, rather than the sound, which is represented first in the auditory brain. PMID- 22046158 TI - Insights from intermittent binocular rivalry and EEG. AB - Novel stimulation and analytical approaches employed in EEG studies of ambiguous figures have recently been applied to binocular rivalry. The combination of intermittent stimulus presentation and EEG source imaging has begun to shed new light on the neural underpinnings of binocular rivalry. Here, we review the basics of the intermittent paradigm and highlight methodological issues important for interpreting previous results and designing future experiments. We then outline current analytical approaches, including EEG microstates, event-related potentials, and statistically based source estimation, and propose a neural model of the sequence of brain events that may underlie different aspects of binocular rivalry. Finally, we discuss the advantages and limitations of using binocular rivalry as a tool to investigate the neural basis of perceptual awareness. PMID- 22046160 TI - Tracing activity across the whole brain neural network with optogenetic functional magnetic resonance imaging. AB - Despite the overwhelming need, there has been a relatively large gap in our ability to trace network level activity across the brain. The complex dense wiring of the brain makes it extremely challenging to understand cell-type specific activity and their communication beyond a few synapses. Recent development of the optogenetic functional magnetic resonance imaging (ofMRI) provides a new impetus for the study of brain circuits by enabling causal tracing of activities arising from defined cell types and firing patterns across the whole brain. Brain circuit elements can be selectively triggered based on their genetic identity, cell body location, and/or their axonal projection target with temporal precision while the resulting network response is monitored non invasively with unprecedented spatial and temporal accuracy. With further studies including technological innovations to bring ofMRI to its full potential, ofMRI is expected to play an important role in our system-level understanding of the brain circuit mechanism. PMID- 22046159 TI - Search-Related Suppression of Hippocampus and Default Network Activity during Associative Memory Retrieval. AB - Episodic memory retrieval involves the coordinated interaction of several cognitive processing stages such as mental search, access to a memory store, associative re-encoding, and post-retrieval monitoring. The neural response during memory retrieval is an integration of signals from multiple regions that may subserve supportive cognitive control, attention, sensory association, encoding, or working memory functions. It is particularly challenging to dissociate contributions of these distinct components to brain responses in regions such as the hippocampus, which lies at the interface between overlapping memory encoding and retrieval, and "default" networks. In the present study, event-related functional magnetic resonance imaging (fMRI) and measures of memory performance were used to differentiate brain responses to memory search from subcomponents of episodic memory retrieval associated with successful recall. During the attempted retrieval of both poorly and strongly remembered word pair associates, the hemodynamic response was negatively deflected below baseline in anterior hippocampus and regions of the default network. Activations in anterior hippocampus were functionally distinct from those in posterior hippocampus and negatively correlated with response times. Thus, relative to the pre-stimulus period, the hippocampus shows reduced activity during intensive engagement in episodic memory search. Such deactivation was most salient during trials that engaged only pre-retrieval search processes in the absence of successful recollection or post-retrieval processing. Implications for interpretation of hippocampal fMRI responses during retrieval are discussed. A model is presented to interpret such activations as representing modulation of encoding-related activity, rather than retrieval-related activity. Engagement in intensive mental search may reduce neural and attentional resources that are otherwise tonically devoted to encoding an individual's stream of experience into episodic memory. PMID- 22046161 TI - Detailed Characterization of Local Field Potential Oscillations and Their Relationship to Spike Timing in the Antennal Lobe of the Moth Manduca sexta. AB - The transient oscillatory model of odor identity encoding seeks to explain how odorants with spatially overlapped patterns of input into primary olfactory networks can be discriminated. This model provides several testable predictions about the distributed nature of network oscillations and how they control spike timing. To test these predictions, 16 channel electrode arrays were placed within the antennal lobe (AL) of the moth Manduca sexta. Unitary spiking and multi site local field potential (LFP) recordings were made during spontaneous activity and in response to repeated presentations of an odor panel. We quantified oscillatory frequency, cross correlations between LFP recording sites, and spike-LFP phase relationships. We show that odor-driven AL oscillations in Manduca are frequency modulating (FM) from ~100 to 30 Hz; this was odorant and stimulus duration dependent. FM oscillatory responses were localized to one or two recording sites suggesting a localized (perhaps glomerular) not distributed source. LFP cross correlations further demonstrated that only a small (r < 0.05) distributed and oscillatory component was present. Cross spectral density analysis demonstrated the frequency of these weakly distributed oscillations was state dependent (spontaneous activity = 25-55 Hz; odor-driven = 55-85 Hz). Surprisingly, vector strength analysis indicated that unitary phase locking of spikes to the LFP was strongest during spontaneous activity and dropped significantly during responses. Application of bicuculline, a GABA(A) receptor antagonist, significantly lowered the frequency content of odor-driven distributed oscillatory activity. Bicuculline significantly reduced spike phase locking generally, but the ubiquitous pattern of increased phase locking during spontaneous activity persisted. Collectively, these results indicate that oscillations perform poorly as a stimulus-mediated spike synchronizing mechanism for Manduca and hence are incongruent with the transient oscillatory model. PMID- 22046162 TI - CFTR and Ca Signaling in Cystic Fibrosis. AB - Among the diverse physiological functions exerted by calcium signaling in living cells, its role in the regulation of protein biogenesis and trafficking remains incompletely understood. In cystic fibrosis (CF) disease the most common CF transmembrane conductance regulator (CFTR) mutation, F508del-CFTR generates a misprocessed protein that is abnormally retained in the endoplasmic reticulum (ER) compartment, rapidly degraded by the ubiquitin/proteasome pathway and hence absent at the plasma membrane of CF epithelial cells. Recent studies have demonstrated that intracellular calcium signals consequent to activation of apical G-protein-coupled receptors by different agonists are increased in CF airway epithelia. Moreover, the regulation of various intracellular calcium storage compartments, such as ER is also abnormal in CF cells. Although the molecular mechanism at the origin of this increase remains puzzling in epithelial cells, the F508del-CFTR mutation is proposed to be the onset of abnormal Ca(2+) influx linking the calcium signaling to CFTR pathobiology. This article reviews the relationships between CFTR and calcium signaling in the context of the genetic disease CF. PMID- 22046163 TI - Complex Interactions between Temperature and Relative Humidity on Water Balance of Adult Tsetse (Glossinidae, Diptera): Implications for Climate Change. AB - Insect water balance plays an important role in determining energy budgets, activity patterns, survival, and population dynamics and, hence, geographic distribution. Tsetse (Glossina spp.) are important vectors of human and animal disease occupying a wide range of habitats in Africa and are notable for their desiccation resistance in xeric environments. Here, we measure water balance and related traits [water loss rate (WLR), body water content (BWC), body lipid content (BLC) and body mass] in adult flies across a range of temperature (20-30 degrees C) and relative humidity (0-99%) combinations in four tsetse species from both xeric and mesic habitats. WLRs were significantly affected by measurement under different temperature and relative humidity combinations, while BWC, BLC, and body mass were less affected. These results provide support for mass independent inter- and intra-specific variation in WLRs and survival times. Furthermore, water balance responses to variation in temperature and relative humidity are complex in Glossina, and this response varies within and among species, subgroups, and ecotypes in terms of both magnitude of effects and the direction of change. Different effects of temperature and relative humidity within and among experimental conditions and species suggests cuticular permeability and saturation deficit are likely to be key factors in forecasting tsetse water balance responses to climate variability. This complicates potential forecasting of tsetse distribution in the face of climate change. PMID- 22046164 TI - Differential glucose uptake in quadriceps and other leg muscles during one-legged dynamic submaximal knee-extension exercise. AB - One-legged dynamic knee-extension exercise (DKE) is a widely used model to study the local cardiovascular and metabolic responses to exercise of the quadriceps muscles. In this study, we explored the extent to which different muscles of the quadriceps are activated during exercise using positron emission tomography (PET) determined uptake of [(18)F]-fluoro-deoxy-glucose (GU) during DKE. Five healthy male subjects performed DKE at 25 W for 35 min and both the contracting and contralateral resting leg were scanned with PET from mid-thigh and distally. On average, exercise GU was the highest in the vastus intermedius (VI) and lowest in the vastus lateralis (VL; VI vs VL, p < 0.05), whereas the coefficient of variation was highest in VL (VL vs VI, p < 0.05). Coefficient of variation between the mean values of the four quadriceps femoris (QF) muscles in the exercising leg was 35 +/- 9%. Compared to mean GU in QF (=100%), GU was on average 73% in VL, 84% in rectus femoris, 115% in vastus medialis, and 142% in VI. Variable activation of hamstring muscles and muscles of the lower leg was also observed. These results show that GU of different muscles of quadriceps muscle group as well as between individuals vary greatly during DKE, and suggests that muscle activity is not equal between quadriceps muscles in this exercise model. Furthermore, posterior thigh muscles and lower leg muscles are more active than hitherto thought even during this moderate exercise intensity. PMID- 22046165 TI - More than meets the eye: age differences in the capture and suppression of oculomotor action. AB - Salient visual stimuli capture attention and trigger an eye-movement toward its location reflexively, regardless of an observer's intentions. Here we aim to investigate the effect of aging (1) on the extent to which salient yet task irrelevant stimuli capture saccades, and (2) on the ability to selectively suppress such oculomotor responses. Young and older adults were asked to direct their eyes to a target appearing in a stimulus array. Analysis of overall performance shows that saccades to the target object were disrupted by the appearance of a task-irrelevant abrupt-onset distractor when the location of this distractor did not coincide with that of the target object. Conditional capture function analyses revealed that, compared to young adults, older adults were more susceptible to oculomotor capture, and exhibited deficient selective suppression of the responses captured by task-irrelevant distractors. These effects were uncorrelated, suggesting two independent sources off age-related decline. Thus, with advancing age, salient visual distractors become more distracting; in part because they trigger reflexive eye-movements more potently; in part because of failing top-down control over such reflexes. The fact that these process-specific age effects remained concealed in overall oculomotor performance analyses emphasizes the utility of looking beyond the surface; indeed, there may be more than meets the eye. PMID- 22046166 TI - The effects of self-report cognitive failures and cognitive load on antisaccade performance. AB - Individuals reporting high levels of distractibility in everyday life show impaired performance in standard laboratory tasks measuring selective attention and inhibitory processes. Similarly, increasing cognitive load leads to more errors/distraction in a variety of cognitive tasks. How these two factors interact is currently unclear; highly distractible individuals may be affected more when their cognitive resources are taxed, or load may linearly affect performance for all individuals. We investigated the relationship between self reported levels of cognitive failures (CF) in daily life and performance in the antisaccade task, a widely used tool examining attentional control. Levels of concurrent cognitive demand were manipulated using a secondary auditory discrimination task. We found that both levels of self-reported CF and task load increased antisaccade latencies while having no effect on prosaccade eye movements. However individuals rating themselves as suffering few daily life distractions showed a comparable load cost to those who experience many. These findings suggest that the likelihood of distraction is governed by the addition of both internal susceptibility and the external current load placed on working memory. PMID- 22046167 TI - Sub- and supralexical information in early phases of lexical access. AB - The present study investigated sub- and supralexical effects in morphological processing for inflected and pseudo complex words and pseudo words in lexical decision with masked and cross-modal priming. The results showed that the early stage of morphological processing is not only sensitive to whether the orthographic string can be segmented into an existing stem and affix, but also whether the full form is an existing word the meaning of which differs from the meaning of the segmented stem. It is thus likely that from early on morphological processing is probably not governed by morpho-orthographic processes alone, but is most likely sensitive to top-down information, perhaps originating from supralexical semantic connections between the words morphological family members. In addition, whereas semantic interpretability has a clear advantage later in processing, this stage seems to be sensitive to bottom-up form information as well. In a detailed theoretical discussion we show how these findings, along with earlier findings, are explained by a model that assumes that morphological information is represented at two interactive levels, corresponding to sublexical form (orthographic) and supralexical (semantic) information mediated by a lexical level. This allows supralexical (semantic) effects to feed top-down, predicting differences between regular inflected and pseudo complex words at the lexical level, affecting the early phases of processing for these words. PMID- 22046168 TI - Grammatical gender inhibition in bilinguals. AB - Inhibitory control processes have been recently considered to be involved in interference resolution in bilinguals at the phonological level. In this study we explored if interference resolution is also carried out by this inhibitory mechanism at the grammatical level. Thirty-two bilinguals (Italian-L1 and Spanish L2) participated. All of them completed two tasks. In the first one they had to name pictures in L2. We manipulated gender congruency between the two languages and the number of presentations of the pictures (1 and 5). Results showed a gender congruency effect with slower naming latencies in the incongruent condition. In the second task, participants were presented with the pictures practiced during the first naming task, but now they were asked to produce the L1 article. Results showed a grammatical gender congruency effect in L1 that increased for those words practiced five times in L2. Our conclusion is that an inhibitory mechanism was involved in the suppression of the native language during a picture naming task. Furthermore, this inhibitory process was also involved in suppressing grammatical gender when it was a source of competition between the languages. PMID- 22046169 TI - Quantification of lateral heterogeneity in carbohydrate permeability of isolated plant leaf cuticles. AB - In phyllosphere microbiology, the distribution of resources available to bacterial colonizers of leaf surfaces is generally understood to be very heterogeneous. However, there is little quantitative understanding of the mechanisms that underlie this heterogeneity. Here, we tested the hypothesis that different parts of the cuticle vary in the degree to which they allow diffusion of the leaf sugar fructose to the surface. To this end, individual, isolated cuticles of poplar leaves were each analyzed for two properties: (1) the permeability for fructose, which involved measurement of diffused fructose by gas chromatography and flame ionization detection (GC-FID), and (2) the number and size of fructose-permeable sites on the cuticle, which was achieved using a green fluorescent protein (GFP)-based bacterial bioreporter for fructose. Bulk flux measurements revealed an average permeance P of 3.39 * 10(-9) ms(-1), while the bioreporter showed that most of the leaching fructose was clustered to sites around the base of shed trichomes, which accounted for only 0.37% of the surface of the cuticles under study. Combined, the GC-FID and GFP measurements allowed us to calculate an apparent rate of fructose diffusion at these preferential leaching sites of 9.15 * 10(-7) ms(-1). To the best of our knowledge, this study represents the first successful attempt to quantify cuticle permeability at a resolution that is most relevant to bacterial colonizers of plant leaves. The estimates for P at different spatial scales will be useful for future models that aim to explain and predict temporal and spatial patterns of bacterial colonization of plant foliage based on lateral heterogeneity in sugar permeability of the leaf cuticle. PMID- 22046170 TI - Improved Immunological Tolerance Following Combination Therapy with CTLA-4/Ig and AAV-Mediated PD-L1/2 Muscle Gene Transfer. AB - Initially thought as being non-immunogenic, recombinant AAVs have emerged as efficient vector candidates for treating monogenic diseases. It is now clear however that they induce potent immune responses against transgene products which can lead to destruction of transduced cells. Therefore, developing strategies to circumvent these immune responses and facilitate long-term expression of transgenic therapeutic proteins is a main challenge in gene therapy. We evaluated herein a strategy to inhibit the undesirable immune activation that follows muscle gene transfer by administration of CTLA-4/Ig to block the costimulatory signals required early during immune priming and by using gene transfer of PD-1 ligands to inhibit T cell functions at the tissue sites. We provide the proof of principle that this combination immunoregulatory therapy targeting two non redundant checkpoints of the immune response, i.e., priming and effector functions, can improve persistence of transduced cells in experimental settings where cytotoxic T cells escape initial blockade. Therefore, CTLA-4/Ig plus PD L1/2 combination therapy represents a candidate approach to circumvent the bottleneck of immune responses directed toward transgene products. PMID- 22046171 TI - Targeting co-stimulatory pathways in gene therapy. AB - Gene therapy with recombinant viral vectors such as adenovirus and adenovirus associated virus holds great promise in treating a wide range of diseases because of the high efficiency with which the viruses transfer their genomes into host cells in vivo. However, the activation of the host immune responses remains a major hurdle to successful gene therapy. Studies in the past two decades have elucidated the important role co-stimulation plays in the activation of both T and B cells. This review summarizes our current understanding of T cell co stimulatory pathways, and strategies targeting these co-stimulatory pathways in gene therapy applications as well as potential future directions. PMID- 22046173 TI - Re-examining the role of hydrogen peroxide in bacteriostatic and bactericidal activities of honey. AB - The aim of this study was to critically analyze the effects of hydrogen peroxide on growth and survival of bacterial cells in order to prove or disprove its purported role as a main component responsible for the antibacterial activity of honey. Using the sensitive peroxide/peroxidase assay, broth microdilution assay and DNA degradation assays, the quantitative relationships between the content of H(2)O(2) and honey's antibacterial activity was established(.) The results showed that: (A) the average H(2)O(2) content in honey was over 900-fold lower than that observed in disinfectants that kills bacteria on contact. (B) A supplementation of bacterial cultures with H(2)O(2) inhibited E. coli and B. subtilis growth in a concentration-dependent manner, with minimal inhibitory concentrations (MIC(90)) values of 1.25 mM/10(7) cfu/ml and 2.5 mM/10(7) cfu/ml for E. coli and B. subtilis, respectively. In contrast, the MIC(90) of honey against E. coli correlated with honey H(2)O(2) content of 2.5 mM, and growth inhibition of B. subtilis by honey did not correlate with honey H(2)O(2) levels at all. (C) A supplementation of bacterial cultures with H(2)O(2) caused a concentration dependent degradation of bacterial DNA, with the minimum DNA degrading concentration occurring at 2.5 mM H(2)O(2). DNA degradation by honey occurred at lower than <=2.5 mM concentration of honey H(2)O(2) suggested an enhancing effect of other honey components. (D) Honeys with low H(2)O(2) content were unable to cleave DNA but the addition of H(2)O(2) restored this activity. The DNase-like activity was heat-resistant but catalase-sensitive indicating that H(2)O(2) participated in the oxidative DNA damage. We concluded that the honey H(2)O(2) was involved in oxidative damage causing bacterial growth inhibition and DNA degradation, but these effects were modulated by other honey components. PMID- 22046172 TI - Acquired antibiotic resistance genes: an overview. AB - In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria. PMID- 22046174 TI - Arsenate Resistance in the Unicellular Marine Diazotroph Crocosphaera watsonii. AB - The toxic arsenate ion can behave as a phosphate analog, and this can result in arsenate toxicity especially in areas with elevated arsenate to phosphate ratios like the surface waters of the ocean gyres. In these systems, cellular arsenate resistance strategies would allow phytoplankton to ameliorate the effects of arsenate transport into the cell. Despite the potential coupling between arsenate and phosphate cycling in oligotrophic marine waters, relatively little is known about arsenate resistance in the nitrogen-fixing marine cyanobacteria that are key components of the microbial community in low nutrient systems. The unicellular diazotroph, Crocosphaera watsonii WH8501, was able to grow at reduced rates with arsenate additions up to 30 nM, and estimated arsenate to phosphate ratios of 6:1. The genome of strain WH8501 contains homologs for arsA, arsH, arsB, and arsC, allowing for the reduction of arsenate to arsenite and the pumping of arsenite out of the cell. The short-term addition of arsenate to the growth medium had no effect on nitrogen fixation. However, arsenate addition did result in the up-regulation of the arsB gene with increasing arsenate concentrations, indicating the induction of the arsenate detoxification response. The arsB gene was also up-regulated by phosphorus stress in concert with a gene encoding the high-affinity phosphate binding protein pstS. Both genes were down regulated when phosphate was re-fed to phosphorus-stressed cells. A field survey of surface water from the low phosphate western North Atlantic detected expression of C. watsoniiarsB, suggestive of the potential importance of arsenate resistance strategies in this and perhaps other systems. PMID- 22046175 TI - Fungicidal Activities and Mechanisms of Action of Pseudomonas syringae pv. syringae Lipodepsipeptide Syringopeptins 22A and 25A. AB - The plant-associated bacterium Pseudomonas syringae pv. syringae simultaneously produces two classes of metabolites: the small cyclic lipodepsinonapeptides such as the syringomycins and the larger cyclic lipodepsipeptide syringopeptins SP22 or SP25. The syringomycins inhibit a broad spectrum of fungi (but particularly yeasts) by lipid-dependent membrane interaction. The syringopeptins are phytotoxic and inhibitory to Gram-positive bacteria. In this study, the fungicidal activities of two major syringopeptins, SP22A and SP25A, and their mechanisms of action were investigated and compared to those of syringomycin E. SP22A and SP25A were observed to inhibit the fungal yeasts Saccharomyces cerevisiae and Candida albicans although less effectively than syringomycin E. S. cerevisiae mutants defective in ergosterol and sphingolipid biosyntheses were less susceptible to SP22A and SP25A but the relative inhibitory capabilities of SRE vs. SP22A and SP25A were maintained. Similar differences were observed for capabilities to cause cellular K(+) and Ca(2+) fluxes in S. cerevisiae. Interestingly, in phospholipid bilayers the syringopeptins are found to induce larger macroscopic ionic conductances than syringomycin E but form single channels with similar properties. These findings suggest that the syringopeptins target the yeast plasma membrane, and, like syringomycin E, employ a lipid dependent channel-forming mechanism of action. The differing degrees of growth inhibition by these lipodepsipeptides may be explained by differences in their hydrophobicities. The more hydrophobic SP22A and SP25A might interact more strongly with the yeast cell wall that would create a selective barrier for their incorporation into the plasma membrane. PMID- 22046176 TI - Fast random permutation tests enable objective evaluation of methods for single subject FMRI analysis. AB - Parametric statistical methods, such as Z-, t-, and F-values, are traditionally employed in functional magnetic resonance imaging (fMRI) for identifying areas in the brain that are active with a certain degree of statistical significance. These parametric methods, however, have two major drawbacks. First, it is assumed that the observed data are Gaussian distributed and independent; assumptions that generally are not valid for fMRI data. Second, the statistical test distribution can be derived theoretically only for very simple linear detection statistics. With nonparametric statistical methods, the two limitations described above can be overcome. The major drawback of non-parametric methods is the computational burden with processing times ranging from hours to days, which so far have made them impractical for routine use in single-subject fMRI analysis. In this work, it is shown how the computational power of cost-efficient graphics processing units (GPUs) can be used to speed up random permutation tests. A test with 10000 permutations takes less than a minute, making statistical analysis of advanced detection methods in fMRI practically feasible. To exemplify the permutation based approach, brain activity maps generated by the general linear model (GLM) and canonical correlation analysis (CCA) are compared at the same significance level. PMID- 22046177 TI - Conditional random fields and supervised learning in automated skin lesion diagnosis. AB - Many subproblems in automated skin lesion diagnosis (ASLD) can be unified under a single generalization of assigning a label, from an predefined set, to each pixel in an image. We first formalize this generalization and then present two probabilistic models capable of solving it. The first model is based on independent pixel labeling using maximum a-posteriori (MAP) estimation. The second model is based on conditional random fields (CRFs), where dependencies between pixels are defined using a graph structure. Furthermore, we demonstrate how supervised learning and an appropriate training set can be used to automatically determine all model parameters. We evaluate both models' ability to segment a challenging dataset consisting of 116 images and compare our results to 5 previously published methods. PMID- 22046178 TI - Lateral information processing by spiking neurons: a theoretical model of the neural correlate of consciousness. AB - Cognitive brain functions, for example, sensory perception, motor control and learning, are understood as computation by axonal-dendritic chemical synapses in networks of integrate-and-fire neurons. Cognitive brain functions may occur either consciously or nonconsciously (on "autopilot"). Conscious cognition is marked by gamma synchrony EEG, mediated largely by dendritic-dendritic gap junctions, sideways connections in input/integration layers. Gap-junction connected neurons define a sub-network within a larger neural network. A theoretical model (the "conscious pilot") suggests that as gap junctions open and close, a gamma-synchronized subnetwork, or zone moves through the brain as an executive agent, converting nonconscious "auto-pilot" cognition to consciousness, and enhancing computation by coherent processing and collective integration. In this study we implemented sideways "gap junctions" in a single-layer artificial neural network to perform figure/ground separation. The set of neurons connected through gap junctions form a reconfigurable resistive grid or sub-network zone. In the model, outgoing spikes are temporally integrated and spatially averaged using the fixed resistive grid set up by neurons of similar function which are connected through gap-junctions. This spatial average, essentially a feedback signal from the neuron's output, determines whether particular gap junctions between neurons will open or close. Neurons connected through open gap junctions synchronize their output spikes. We have tested our gap-junction-defined sub network in a one-layer neural network on artificial retinal inputs using real world images. Our system is able to perform figure/ground separation where the laterally connected sub-network of neurons represents a perceived object. Even though we only show results for visual stimuli, our approach should generalize to other modalities. The system demonstrates a moving sub-network zone of synchrony, within which the contents of perception are represented and contained. This mobile zone can be viewed as a model of the neural correlate of consciousness in the brain. PMID- 22046179 TI - Biochemical frequency control by synchronisation of coupled repressilators: an in silico study of modules for circadian clock systems. AB - Exploration of chronobiological systems emerges as a growing research field within bioinformatics focusing on various applications in medicine, agriculture, and material sciences. From a systems biological perspective, the question arises whether biological control systems for regulation of oscillatory signals and their technical counterparts utilise similar mechanisms. If so, modelling approaches and parameterisation adopted from building blocks can help to identify general components for frequency control in circadian clocks along with gaining insight into mechanisms of clock synchronisation to external stimuli like the daily rhythm of sunlight and darkness. Phase-locked loops could be an interesting candidate in this context. Both, biology and engineering, can benefit from a unified view resulting from systems modularisation. In a first experimental study, we analyse a model of coupled repressilators. We demonstrate its ability to synchronise clock signals in a monofrequential manner. Several oscillators initially deviate in phase difference and frequency with respect to explicit reaction and diffusion rates. Accordingly, the duration of the synchronisation process depends on dedicated reaction and diffusion parameters whose settings still lack to be sufficiently captured analytically. PMID- 22046180 TI - A reinforcement learning framework for spiking networks with dynamic synapses. AB - An integration of both the Hebbian-based and reinforcement learning (RL) rules is presented for dynamic synapses. The proposed framework permits the Hebbian rule to update the hidden synaptic model parameters regulating the synaptic response rather than the synaptic weights. This is performed using both the value and the sign of the temporal difference in the reward signal after each trial. Applying this framework, a spiking network with spike-timing-dependent synapses is tested to learn the exclusive-OR computation on a temporally coded basis. Reward values are calculated with the distance between the output spike train of the network and a reference target one. Results show that the network is able to capture the required dynamics and that the proposed framework can reveal indeed an integrated version of Hebbian and RL. The proposed framework is tractable and less computationally expensive. The framework is applicable to a wide class of synaptic models and is not restricted to the used neural representation. This generality, along with the reported results, supports adopting the introduced approach to benefit from the biologically plausible synaptic models in a wide range of intuitive signal processing. PMID- 22046181 TI - Ipilimumab, a promising immunotherapy with increased overall survival in metastatic melanoma? AB - Malignant melanoma (MM) is one of the most aggressive skin cancer. The therapeutic options remain limited for advanced MM, and those directed to the neoplastic cells have not brought major survival advantage so far. Immunotherapy is another targeted option. Ipilimumab, a monoclonal antibody directed to CTLA-4 present on cytotoxic T cells boosts immunity, particularly its anti-MM activity. Under treatment, the overall survival of patients with MM metastases is moderately but significantly increased. The immuno-related adverse effects may be severe and life threatening. PMID- 22046182 TI - Comparative Evaluation of the Safety and Efficacy of Long-Term Use of Imidafenacin and Solifenacin in Patients with Overactive Bladder: A Prospective, Open, Randomized, Parallel-Group Trial (the LIST Study). AB - Objectives. Overactive bladder (OAB) is a chronic disease, but comparative trials of anticholinergics, which are commonly used for treatment of OAB, have generally been performed for up to 12 weeks only. There is no comparative study of a long term intervention. Methods. We conducted a 52-week prospective randomized comparative study to evaluate the efficacy and tolerability of two anticholinergics. Results. Forty-one Japanese patients with untreated OAB were randomly assigned to imidafenacin and solifenacin groups. There was no difference in OABSS and KHQ scores between the two groups, but the severity and incidence of adverse events caused by the anticholinergics showed increased differences between the groups with time. The severity of dry mouth and the incidence of constipation were significantly lower in the imidafenacin group (P = 0.0092 and P = 0.0013, resp.). Conclusions. This study is the first long-term trial to show differences in the properties of anticholinergics that were not detected in short term studies. Since OAB is a chronic disease, we conclude that imidafenacin is preferable to solifenacin from a perspective of safety. PMID- 22046183 TI - Sexual Dysfunctions of HIV-Positive Men: Associated Factors, Pathophysiology Issues, and Clinical Management. AB - Sexual dysfunctions in HIV-positive men are associated with an increase in risky sexual behavior and decreased adherence to antiretroviral drug regimens. Because of these important public health issues, we reviewed the literature on the pathophysiology, associated factors and clinical management of sexual dysfunction in HIV-positive men. The goal was to investigate the current research on these issues. Literature searches were performed in June 2011 on PubMed, Web of Science, and PsycInfo databases with the keywords "AIDS" and "sexual dysfunction" and "HIV" and "sexual dysfunction", resulting in 54 papers. Several researchers have investigated the factors associated with sexual dysfunction in HIV-positive men. The association between sexual dysfunction and antiretroviral drugs, particularly protease inhibitors, has been reported in many studies. The lack of standardized measures in many studies and the varying study designs are the main reasons that explain the controversial results. Despite some important findings, the pathophysiology of sexual dysfunction in the HAART era still not completely understood. Clinical trials of testosterone replacement therapy have shown the treatment to be beneficial to the improvement of sexual dysfunctions related to hypogonadism. However, there are not enough psychological intervention studies to make conclusions regarding the therapeutic effects of psychotherapy. PMID- 22046184 TI - Male infertility and its causes in human. AB - Infertility is one of the most serious social problems facing advanced nations. In general, approximate half of all cases of infertility are caused by factors related to the male partner. To date, various treatments have been developed for male infertility and are steadily producing results. However, there is no effective treatment for patients with nonobstructive azoospermia, in which there is an absence of mature sperm in the testes. Although evidence suggests that many patients with male infertility have a genetic predisposition to the condition, the cause has not been elucidated in the vast majority of cases. This paper discusses the environmental factors considered likely to be involved in male infertility and the genes that have been clearly shown to be involved in male infertility in humans, including our recent findings. PMID- 22046185 TI - Dynamic Production of Soluble Extracellular Polysaccharides by Streptococcus mutans. AB - Caries development in the presence of Streptococcus mutans is associated not only with the production of extracellular water-insoluble polymers but also is based on water-soluble polysaccharides. The aim of this study was the evaluation of a novel glucan-specific Lectin assay for monitoring water-soluble EPS produced by S. mutans during several growth periods in different media. S. mutans cultures were grown for 24 h, 48 h, and 144 h in medium deficient of sucrose (A) and medium supplemented with 5% sucrose (B). Microtiter well plates were coated with cell-free supernatants followed by the addition of labeled Concanavalin-A and enzyme substrate. The substrate reactions were kinetically detected at 405 nm. The validation of the assay was performed using carbohydrates dextran, xanthan, and sucrose as reference. This new Concanavalin-A-based assay showed the highest sensitivity for dextran and revealed that the glucan production of S. mutans reached its maximum at 144 h in medium B according to bacterial maturation. PMID- 22046186 TI - Prevalence of Oral Manifestations and Their Association with CD4/CD8 Ratio and HIV Viral Load in South India. AB - The objective of the present research was to determine the prevalence of oral manifestations in an HIV infected population from south India and evaluate their association with HIV viral load and CD4/CD8 ratio. Intraoral examination of 103 patients, whose CD4/CD8 ratio was available, were conducted. HIV viral loads were available for thirty patients only. The prevalence of oral manifestations was 80.6% (83/103). The most common oromucosal lesion was erythematous candidiasis (EC) (38.8%) followed by melanotic hyperpigmentation (35.9%). Patients having any oral manifestation had a mean CD4/CD8 ratio of 0.24. EC had positive predictive value of 85.0% for CD4/CD8 ratio <0.30. The prevalence of oral manifestations in patients taking ART was lesser (78.6%) as compared to patients not taking ART (82%). Patients having any oral manifestation had a higher HIV viral load as compared to patients not having any oral manifestations (P < 0.05). Pseudomembranous candidiasis (PC) was significantly associated with higher HIV viral loads (>20,000 copies/mL) (P < 0.05). Patients having EC had 4 times greater chance of having CD4/CD8 ratio <0.30. PC can be considered as a marker of immune suppression (HIV viral load >20,000 copies/mL). PMID- 22046187 TI - Bacillus Strains Most Closely Related to Bacillus nealsonii Are Not Effectively Circumscribed within the Taxonomic Species Definition. AB - Bacillus strains with >99.7% 16S rRNA gene sequence similarity were characterized with DNA:DNA hybridization, cellular fatty acid (CFA) analysis, and testing of 100 phenotypic traits. When paired with the most closely related type strain, percent DNA:DNA similarities (% S) for six Bacillus strains were all far below the recommended 70% threshold value for species circumscription with Bacillus nealsonii. An apparent genomic group of four Bacillus strain pairings with 94% 70% S was contradicted by the failure of the strains to cluster in CFA- and phenotype-based dendrograms as well as by their differentiation with 9-13 species level discriminators such as nitrate reduction, temperature range, and acid production from carbohydrates. The novel Bacillus strains were monophyletic and very closely related based on 16S rRNA gene sequence. Coherent genomic groups were not however supported by similarly organized phenotypic clusters. Therefore, the strains were not effectively circumscribed within the taxonomic species definition. PMID- 22046188 TI - The lyon clinical olfactory test: validation and measurement of hyposmia and anosmia in healthy and diseased populations. AB - The LCOT is a self-administered test designed to assess olfactory deficits. Altogether, 525 subjects contributed to the validation. Elderly participants were well represented in this sample. In a validation study (study 1), 407 healthy and 17 anosmic volunteers between 15 and 91 years of age underwent threshold, supraliminal detection, and identification testing. Cutoff values for normosmia and hyposmia were calculated and applied in a second study in a group of patients with smell complaints and in a group of Alzheimer patients with age-matched controls. Incidence of smell deficit was estimated at 5.6% in the healthy population of study 1, and at 16% in the elderly control group of study 2. Assessment of the ability of each subtest to discriminate between groups showed that LCOT is relevant to differentiating between perception and identification deficits and between Alzheimer's and hyposmic patients. PMID- 22046189 TI - A Human Head and Neck Squamous Cell Carcinoma Cell Line with Acquired cis Diamminedichloroplatinum-Resistance Shows Remarkable Upregulation of BRCA1 and Hypersensitivity to Taxane. AB - Recently, an inverse relationship between resistance to platinum-based chemotherapeutic agents and taxanes has been implicated in breast and ovarian cancers, and a possible pivotal role for BRCA1 has also been suggested. Because cis-diamminedichloroplatinum (CDDP) and taxanes are the most active antitumor agents against head and neck squamous cell carcinoma (HNSCC), we analyzed the sensitivity of nine HNSCC cell lines and their previously established derived CDDP-resistant cell lines to two representative taxanes: docetaxel and paclitaxel. None of the nine original cell lines showed any cross resistance between CDDP and taxanes, but one of the CDDP-resistant cell lines, RPMI2650CR, demonstrated hypersensitivity to both taxanes when compared to the parental cell line, RPMI2650. Furthermore, RPMI2650CR exhibited increased expression of BRCA1. These data suggest that (i) taxanes are a good candidate for a second-line therapeutic drug for HNSCC patients with acquired CDDP resistance and (ii) BRCA1 can be a candidate marker for predicting an inverse CDDP/taxane sensitivity phenotype in HNSCC. PMID- 22046190 TI - Measuring Urinary Sensation with Current Perception Threshold: A Comparison between Method of Limits and Method of Levels. AB - Purpose. To determine the association between the two methods of obtaining current perception thresholds (CPTs) in the lower urinary tract (LUT). Materials and Methods. Twenty-one women undergoing pelvic surgery underwent CPT determinations of the urethra. CPTs were measured at 2,000, 250, and 5 Hz (corresponding to A-beta, A-delta, and C fibers, resp.) both pre- and postoperatively. Threshold values were obtained in all patients by using the method of limits and the method of levels. Results. CPT values obtained by using the method of levels and the methods of limits were highly correlated at all frequencies before and after surgery (rho = 0.93-0.99, P < 0.0001). The mean threshold values obtained by the method of levels were significantly lower at all frequencies compared with those obtained by the method of limits. Conclusions. Our findings suggest that the method of levels is more sensitive for the detection of CPTs compared to the method of limits. PMID- 22046191 TI - Elizabethkingia meningosepticum (Chryseobacterium meningosepticum) Infections in Children. AB - Chryseobacterium meningosepticum is a ubiquitous Gram-negative bacillus historically associated primarily with meningitis in neonates and a wide variety of infections in immunocompromised patients. Neonatal infections often occur as outbreaks with environmental contamination being the source. C. meningosepticum infections are not common but are clinically important because the organism is naturally resistant to multiple antibiotics. In this paper, we have reviewed the nosocomial outbreaks of C. meningosepticum in newborns and infants reported so far in the literature and overviewed the infection control interventions, treatment modalities, and prevention measures. PMID- 22046192 TI - An evaluation of initial vancomycin dosing in infants, children, and adolescents. AB - Background. The pharmacokinetics of many medications change as we age, thus most would assume dosing strategies would adjust for these changes. The objective of this study is to evaluate the initial vancomycin dosing in three pediatric age groups based on measured serum trough concentrations. Methodology. This retrospective database review included patients aged from 1 month to 18 years old admitted to the Moses H. Cone Memorial Hospital. Patients had to have received vancomycin dosed at 15 mg/kg every 8 hours with an appropriately measured trough concentration. The primary outcome was to determine the percentage of patients in 3 pediatric age groups achieving therapeutic trough concentrations with the initial vancomycin dosing regimen. Results. Twenty-five patients were included in the study. None of the patients had therapeutic trough concentrations after receiving vancomycin 15 mg/kg every 8 hours. Only one patient had a supratherapeutic level, while all of the other patients had levels less than 10 mcg/mL. Conclusions. Vancomycin 15 mg/kg every 8 hours did not provide therapeutic serum trough concentrations for any pediatric age groups. Higher doses and/or more frequent dosing regimens need to be evaluated for each age group to determine the most appropriate strategies for producing therapeutic trough concentrations. PMID- 22046193 TI - Evaluation of trace metal levels in tissues of two commercial fish species in Kapar and Mersing coastal waters, Peninsular Malaysia. AB - This study is focused on evaluating the trace metal levels in water and tissues of two commercial fish species Arius thalassinus and Pennahia anea that were collected from Kapar and Mersing coastal waters. The concentrations of Fe, Zn, Al, As, Cd and Pb in these coastal waters and muscle, liver and gills tissues of the fishes were quantified. The relationship among the metal concentrations and the height and weight of the two species were also examined. Generally, the iron has the highest concentrations in both water and the fish species. However, Cd in both coastal waters showed high levels exceeding the international standards. The metal level concentration in the sample fishes are in the descending order livers > gills > muscles. A positive association between the trace metal concentrations and weight and length of the sample fishes was investigated. Fortunately the level of these metal concentrations in fish has not exceeded the permitted level of Malaysian and international standards. PMID- 22046194 TI - PI3K functions in cancer progression, anticancer immunity and immune evasion by tumors. AB - The immunological surveillance of tumors relies on a specific recognition of cancer cells and their associate antigens by leucocytes of innate and adaptive immune responses. However, a dysregulated cytokine release can lead to, or be associated with, a failure in cell-cell recognition, thus, allowing cancer cells to evade the killing system. The phosphatidylinositol 3-kinase (PI3K) pathway regulates multiple cellular processes which underlie immune responses against pathogens or malignant cells. Conversely, there is accumulating evidence that the PI3K pathway is involved in the development of several malignant traits of cancer cells as well as their escape from immunity. Herein, we review the counteracting roles of PI3K not only in antitumor immune response but also in the mechanisms that cancer cells use to avoid leukocyte attack. In addition, we discuss, from antitumor immunological point of view, the potential benefits and disadvantages arising from use of anticancer pharmacological agents targeting the PI3K pathway. PMID- 22046195 TI - NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity. AB - HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB 231) and rat glioma cells (C6), with an IC(50) ranging from 8.5 to 10.3 MUM. Western blot demonstrated that levels of p21((Waf1/Cip1)), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD 1. After NBM-HD-1 treatment for 1-4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1, p21((Waf1/Cip1)) gene expression had markedly increased while cyclin B1 and D1 gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor gene p53 in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activity in vitro and in vivo. PMID- 22046196 TI - Clinical aspects of Marburg hemorrhagic fever. AB - Marburg virus belongs to the genus Marburgvirus in the family Filoviridae and causes a severe hemorrhagic fever, known as Marburg hemorrhagic fever (MHF), in both humans and nonhuman primates. Similar to the more widely known Ebola hemorrhagic fever, MHF is characterized by systemic viral replication, immunosuppression and abnormal inflammatory responses. These pathological features of the disease contribute to a number of systemic dysfunctions including hemorrhages, edema, coagulation abnormalities and, ultimately, multiorgan failure and shock, often resulting in death. A detailed understanding of the pathological processes that lead to this devastating disease remains elusive, a fact that contributes to the lack of licensed vaccines or effective therapeutics. This article will review the clinical aspects of MHF and discuss the pathogenesis and possible options for diagnosis, treatment and prevention. PMID- 22046198 TI - A comparison of Stone Cone versus lidocaine jelly in the prevention of ureteral stone migration during ureteroscopic lithotripsy. AB - BACKGROUND: Intracorporeal lithotripsy modalities and stone removal devices have been created to facilitate endoscopic management of ureteral stones. These devices, along with improved techniques, have resulted in stone-free rates greater than 95% with low morbidity. However, problems remain that preclude consistent 100% stone-free rates with endoscopic treatment of ureteral calculi. Retrograde migration during ureteroscopic procedures remains a significant problem. OBJECTIVES: The aim of this study was to compare the Stone Cone device and instillation of lubricating lidocaine jelly as two methods to prevent retrograde stone migration during ureteroscopic lithotripsy. PATIENTS AND METHODS: This study included patients suffering from ureteral stones that were treated with intracorporeal lithotripsy using the pneumatic Lithoclast. These patients were divided into two groups. In group I, the Stone Cone device was used, while in group II, lidocaine jelly 2% concentration was used. RESULTS: This study included 40 patients with a mean age of 38.6 +/- 9.3 years (20 patients in each group). There was no significant difference between the groups with regards to stone site, size or state of the upper urinary tract by excretory urography. The pneumatic Lithoclast allowed successful fragmentation of all calculi into small fragments. Upward stone migration did not occur in patients in the Stone Cone group, while in the lidocaine jelly group it occurred in three patients (15%). The operative time in the Stone Cone group ranged between 30 and 55 minutes (mean, 41.8 +/- 5.3), while in the lidocaine jelly group it ranged between 40 and 71 minutes (mean, 51.4 +/- 3.4), and this difference was statistically significant (p < 0.05). CONCLUSION: The Stone Cone is safe and efficient in preventing proximal stone migration during ureteroscopic pneumatic lithotripsy. It maintained continuous ureteral access and demonstrated a statistically significant advantage over the lidocaine jelly in terms of proximal stone migration, operative time, and the need for auxiliary procedures. PMID- 22046197 TI - Immunomodulation by vitamin D: implications for TB. AB - TB remains a major cause of mortality throughout the world. Low vitamin D status has been linked to increased risk of TB and other immune disorders. These observations suggest a role for vitamin D as a modulator of normal human immune function. This article will detail the cellular and molecular mechanisms by which vitamin D regulates the immune system and how vitamin D insufficiency may lead to immune dysregulation. The importance of vitamin D bioavailability as a mechanism for defining the immunomodulatory actions of vitamin D and its impact on TB will also be discussed. The overall aim will be to provide a fresh perspective on the potential benefits of vitamin D supplementation in the prevention and treatment of TB. PMID- 22046199 TI - Medical therapy for premature ejaculation. AB - Premature ejaculation (PE) is a common male sexual dysfunction. Advances in PE research have been hampered owing to a nonstandardized definition of PE, until the definition by the International Society of Sexual Medicine (ISSM) in 2009. Once the diagnosis of PE is established through a thorough history, a variety of medical therapies is available, including tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), centrally acting opiates, phosphodiesterase 5 inhibitors and topical desensitizing creams. Most of these treatments increase the intravaginal ejaculation latency time (IELT) and patient satisfaction scores, with the most convincing evidence for SSRIs and topical creams. Daily SSRIs such as paroxetine, although efficacious, do have a substantial and prolonged side effect profile. Dapoxetine, which is a on-demand SSRI, is the only licensed drug for the treatment of PE, increasing IELT by a factor of 2.5 to 3 with limited and tolerable side effects. In the near future, the topical aerosol PSD502 is due to be licensed for the treatment of PE, increasing IELT by up to a factor of 6 but having minimal local and negligible systemic side effects. PMID- 22046200 TI - The role of sodium hyaluronate and sodium chondroitin sulphate in the management of bladder disease. AB - Bladder epithelium is not only a simple defence against infections, but it is also a specialized tissue regulating complex bladder functions and playing an active role in the pathogenesis of many bladder diseases. There is strong evidence that different chronic inflammatory bladder diseases, such as recurrent urinary tract infection (UTI), chemical or radiation cystitis and painful bladder syndrome/interstitial cystitis (PBS/IC), can be pathophysiologically linked in the first step of the disease to the loss of the glycosaminoglycan (GAG) mucous layer independently of the original cause of the inflammatory process. The aim of this article is to review the current evidence on the clinic applications of GAGs in urology, with particular emphasis on the therapeutic use of hyaluronic acid (HA) and chondroitin sulphate (CS). A comprehensive electronic literature search was conducted in May 2011 using the Medline database. Three studies supported the decrease of the rate of recurrent UTIs by restoring the GAG layer, showing a significant reduction of UTI rates and a prolonged median time to recurrence after HA intravesical instillations in women with recurrent UTI. We provide higher level evidence by reporting a prospective, randomized, double-blind, placebo-controlled study on the use of intravesical HA and CS in women with recurrent UTIs. A significant reduction of 77% in the UTI rate per patient per year versus placebo was observed at the end of the study. Nine studies were published between 2002 and 2011 on the use of HA and CS to treat PBS/IC. Three of them evaluated the use of GAGs bladder instillation to prolong the effects of bladder hydrodistension. In the other six studies the efficacy of HA bladder instillations to reduce symptoms score was assessed. Preliminary studies support data on the role of HA-CS in detrusor overactivity, nonbacterial cystitis and urological malignancies. Few data are available regarding the mode of action of HA-CS or its effectiveness in the management of bladder diseases. The major issue in interpreting the available evidence regarding HA-CS is that most of the reported studies are nonrandomized and without a control arm. HA-CS may be considered for further studies, including randomized, controlled trials with adequate power. PMID- 22046201 TI - 3-d volumetric evaluation of human mandibular growth. AB - Bone growth is a complex process that is controlled by a multitude of mechanisms that are not fully understood.Most of the current methods employed to measure the growth of bones focus on either studying cadaveric bones from different individuals of different ages, or successive two-dimensional (2D) radiographs. Both techniques have their known limitations. The purpose of this study was to explore a technique for quantifying the three dimensional (3D) growth of an adolescent human mandible over the period of one year utilizing cone beam computed tomography (CBCT) scans taken for regular orthodontic records. Three dimensional virtual models were created from the CBCT data using mainstream medical imaging software. A comparison between computer-generated surface meshes of successive 3-D virtual models illustrates the magnitude of relative mandible growth. The results of this work are in agreement with previously reported data from human cadaveric studies and implantable marker studies. The presented method provides a new relatively simple basis (utilizing commercially available software) to visualize and evaluate individualized 3D (mandibular) growth in vivo. PMID- 22046202 TI - Pedicle Screw Surgery in the UK and Ireland: A Questionnaire Study. AB - Pedicle screw (PS) malpositioning rates are high in spine surgery. This has resulted in the use of computed navigational aids to reduce the rate of malposition; but these are often expensive and limited in availability. A simple mechanical device to aid PS insertion might overcome some of these disadvantages. The purpose of this study was to determine the demand and design criteria for a simple device to aid PS placement, as well as to collect opinions and experiences on PS surgery in the UK and Ireland. A postal questionnaire was sent to 422 spinal surgeons in the UK and Ireland. 101 questionnaires were received; 67 of these (16% of total sent) contained useful information. 78% of surgeons experienced problems with PS placement. The need for a simple mechanical device to aid PS placement was expressed by 59% of respondent surgeons. The proportion of respondents that inserted PSs in the cervical spine was 14%; PSs are mainly inserted in the thoracic, lumbar and sacral spine, but potential exists for a PS placement aid for the cervical and thoracic spine. From the experiences of these 67 surgeons, there is evidence to suggest that surgeons would prefer a pedicle aid that is multiple use, one-piece, hand-held, radiolucent, unilateral and uses the line of sight principle in traditional open surgery. Based on the experiences of 67 surgeons, there is evidence to suggest that computed navigational aids are not readily used in PS surgery and that a simple mechanical device could be a better option. This paper provides useful data for improving the outcomes of spinal surgery. PMID- 22046203 TI - Pregnant women with epilepsy in a developing country. AB - This is the first prospective study carried out in Argentina and Latin America to provide the impact of epilepsy throughout the childbearing years life of women, and pregnancy outcome in a population of pregnant women with diagnosis of epilepsy and antiepileptics drugs (AEDs). Ninety-four women were studied prospectively at the Epilepsy Center, the largest in Argentina. Of the 94 women examined in this study only 10% planned their pregnancy and received folic acid before conception.More than half of women in our study were on monotherapy, with the most frequently prescribed drugs being carbamazepine and valproic acid. In all, 90.4% of the women had a normal pregnancy and delivery. There were 8.5% spontaneous abortions. Major congenital malformations (MCM) was detected in 10.6% of newborns at birth; in the general population it varies between 1.6-3.2%. The results from this study are helpful in the highlighting correct gaps in knowledge in this population group. PMID- 22046204 TI - An immunological analysis of dystroglycan subunits: lessons learned from a small cohort of non-congenital dystrophic patients. AB - The dystroglycan (DG) expression pattern can be altered in severe muscular dystrophies. In fact, some congenital muscular dystrophies (CMDs) and limb-girdle muscular dystrophies (LGMDs) are caused by point mutations identified in six glycosyltransferase genes which are likely to target different steps along the posttranslational "O-glycosylation route" leading to a fully decorated and functional alpha-DG subunit. Indeed, hypoglycosylation of alpha-DG is thought to represent a major pathological event, in that it could reduce the DG's ability to bind the basement membrane components, thus leading to sarcolemmal instability and necrosis. In order to set up an efficient standard immunological protocol, taking advantage of a wide panel of antibodies, we have analyzed the two DG subunits in a small cohort of adult dystrophic patients, whom an extensive medical examination had already clinically classified as affected by LGMD (5), Miyoshi (1) or distal (1) myopathy. Immunofluorescence analysis of skeletal muscle tissue sections revealed a proper sarcolemmal localization of the DG subunits in all the patients analyzed. However, Western blot analysis of lectin enriched skeletal muscle samples revealed an abnormal glycosylation of alpha-DG in two patients. Our work reinforces the notion that a careful immunological and biochemical analysis of the two DG subunits should be always considered as a prerequisite for the identification of new putative cases of dystroglycanopathy. PMID- 22046205 TI - The Frequency of A1298C and C677T Polymorphisms of the Methylentetrahydrofolate Gene in Turkish Patients with Rheumatoid Arthritis: Relationship with Methotrexate Toxicity. AB - The C677T and A1298C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine the frequency of MTHFR C677 T and A1298C gene polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity.Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 +/-12.5 and 46.2 +/- 13.4 years, were enrolled to the study. Demographic characteristics were obtained and MTX-related adverse effects were recorded in the patient group. The A1298C and C677T polymorphisms of the MTHFR gene were analyzed and the distribution of genotypes according side effects, were determined.The frequency of MTHFR C677T and A1298C polymorphisms were similar in the patient and control groups. Folic acid supplementation with a mean dose of 5mg folic acid/week, was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment, and MTX had been discontinued in 12 (18.8%) patients due to side effects and/or inefficacy. MTHFR C677T and A1298C gene polymorphisms were found to be similar in patients with and without MTX-related adverse events.In conclusion, A1298C and C677T polymorphisms in the MTHFR gene, were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible from the MTX toxicity in patients suffering from RA. PMID- 22046206 TI - Efficacy of transcranial direct current stimulation coupled with a multidisciplinary rehabilitation program for the treatment of fibromyalgia. AB - Pain control in fibromyalgia patients is limited no matter the therapeutic regimens used. Recent data have shown that daily sessions of anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) in patients with fibromyalgia (FM) are associated with reduction of pain perception. OBJECTIVE: We aimed to test whether active tDCS, as compared with sham tDCS, combined with multidisciplinary rehabilitation is associated with significant clinical gains in fibromyalgia. DESIGN: This was a randomized, double-blinded controlled trial. SUBJECTS: 23 patients were randomized to receive weekly sessions of multidisciplinary rehabilitation approach combined with sham or anodal tDCS of M1. Patients were evaluated for pain with VAS and for quality of life with SF-36, fibromyalgia pain questionnaire and health assessment questionnaire by a blinded rater before and after the 4 month period of rehabilitation. RESULTS: Patients tolerated tDCS treatment well, without adverse effects. Patients who received active treatment had a significantly greater reduction of SF-36 pain domain scores (F((2,21))=6.57; p=0.006) and a tendency of higher improvement in Fibromyalgia Impact Questionnaire (FIQ) scores after (p=0.056) as compared with sham tDCS/standard treatment, but no differences were observed in the other domains. CONCLUSIONS: Although active tDCS was associated with superior results in one domain (SF-36 pain domain), the lack of significance in the other domains does not fully support this strategy (weekly tDCS) combined with a multidisciplinary approach. PMID- 22046207 TI - The association of disability and pain with individual and community socioeconomic status in people with hip osteoarthritis. AB - OBJECTIVE: To examine associations between disability and socioeconomic status (SES) in persons with hip radiographic OA (rOA) or symptomatic OA (sxOA) in the Johnston County Osteoarthritis Project. METHODS: Cross-sectional analyses were conducted on individuals with hip rOA (708) or sxOA (251). rOA was defined as Kellgren-Lawrence >= 2. Educational attainment (<12 years or >=12 years) and occupation (managerial or non-managerial) were individual SES measures. Census block group poverty rate (<12%, 12-25%, >=25%) was the community SES measure. Disability was measured by the HAQ-DI and the WOMAC (function, pain, total). Covariates included age, gender, race, BMI, and presence of knee symptoms. Analyses examined associations of disability with each SES effect separately, followed by multivariable analyses using all SES variables, adjusting for covariates. RESULTS: In models with single SES variables adjusted for covariates, WOMAC scores were associated significantly (p<0.05) with low educational attainment and non-managerial occupation in rOA and sxOA. HAQ was significantly associated with low educational attainment in rOA and sxOA and with high community poverty in rOA. In models including all SES variables, the patterns of association were similar although with diminished significance. There was indication that education was more strongly associated with HAQ and WOMAC function, while occupation was more strongly associated with WOMAC pain. CONCLUSION: Our data provide evidence that individual SES is an important factor to consider when examining disability and pain outcomes in older adults with hip OA. PMID- 22046208 TI - Lack of CTGF*-945C/G Dimorphism in Thai Patients with Systemic Sclerosis. AB - An association between connective tissue growth factor (CTGF) gene dimorphism at 945 (CTGF*-945C/G) and systemic sclerosis (SSc) has been reported with inconclusive results. We performed this study to determine whether such an association exists among Thai patients with SSc. DNA samples were taken from 50 Thai SSc patients (diffuse SSc in 39 and limited SSc in 11) and 99 healthy controls for determination of CTGF*-945C/G dimorphism by polymerase chain reaction (PCR) using specific oligonucleotide primers. The associations between the genotype frequencies, clinical manifestations and auto-antibodies were determined as well. When compared with the controls, SSc patients had no significantly higher frequencies of the GG genotype (44.0% vs 39.4%, p = 0.60), G allele (63.0% vs 65.2%, p = 0.80) or G phenotype (82.0% vs 90.9%, p = 1.0). There was no association between the presence of the GG genotype and clinical manifestations (pulmonary fibrosis, sclerodactyly, digital pitting scars, telangiectasia and pulmonary arterial hypertension), or the presence of auto antibodies (anti-Scl-70, anti-SSA/Ro, and anti-RNP). In conclusion, we found no association between CTGF*-945C/G dimorphism and Thai SSc patients. PMID- 22046209 TI - The Anti-Apoptotic Effect of Respiratory Syncytial Virus on Human Peripheral Blood Neutrophils is Mediated by a Monocyte Derived Soluble Factor. AB - Respiratory Syncytial Virus (RSV) causes annual epidemics of respiratory disease particularly affecting infants. The associated airway inflammation is characterized by an intense neutrophilia. This neutrophilic inflammation appears to be responsible for much of the pathology and symptoms. Previous work from our group had shown that there are factors within the airways of infants with RSV bronchiolitis that inhibit neutrophil apoptosis. This study was undertaken to determine if RSV can directly affect neutrophil survival.NEUTROPHILS WERE ISOLATED FROM CITRATED VENOUS BLOOD (COLLECTED FROM HEALTHY ADULT VOLUNTEERS) BY DISCONTINUOUS PLASMA: Percoll gradient centrifugation and, in some experiments, further purified by negative immunomagnetic bead selection. The effect of RSV on neutrophil survival was measured by Annexin V-PE /To-Pro-3 staining and by morphological changes, using Dif-Quick staining of cytospins.Inhibition of neutrophil apoptosis was observed in neutrophils isolated by standard plasma:Percoll gradient when exposed to RSV but not in ultra pure neutrophil preparations. Adding monocytes back to ultra purified preparations restored the effect. The inhibition of apoptosis was observed with both active and UV inactivated virus. The effect is dependent on a soluble factor and appears to be dependent on CD14 receptors on the monocytes. PMID- 22046210 TI - Development and Psychometric Evaluation of the Instrument: Attitudes Towards Organ Donor Advocacy Scale (ATODAS). AB - The consequences of advocacy in nursing are critical when caring for a potential organ donor. No specific instrument has been available to measure attitudes toward organ donor advocacy. The aim of this study was to develop and psychometrically evaluate an instrument for measuring intensive and critical care (ICU) nurses' attitudes toward organ donor advocacy. The study was conducted in two stages: instrument development and instrument evaluation and refinement. A questionnaire was developed (Attitude Toward Organ Donor Advocacy Scale (ATODAS)), which was sent to half of all nurses working in ICUs (general-, neuro , thoracic- or paediatric-) in Sweden (n=1180). The final response rate was 42.5% (n=502). In order to explore validity and reliability, the expected scale dimensionality of the questionnaire was examined both by explorative principal component analysis (with oblique, varimax rotation) and by confirmatory multi trait analysis. The confirmatory factor analysis indicated that the ATODAS could best be explained by five factors; Attitudes toward championing organ donation at a structural hospital level; Attitudes toward championing organ donation at a political and research level; Attitudes toward actively and personally safeguarding the will and wishes of the potential organ donor, Attitudes toward safeguarding the potential donor's will and wishes by a professional approach and Attitudes toward safeguarding the will and wishes of the relatives. This initial testing indicated that the ATODAS has good psychometric properties and can be used in future research to explore if interventions may influence attitudes and behaviors related to organ donor advocacy. PMID- 22046211 TI - Immune Responses of HIV-1 Tat Transgenic Mice to Mycobacterium Tuberculosis W Beijing SA161. AB - BACKGROUND: Mycobacterium tuberculosis remains among the leading causes of death from an infectious agent in the world and exacerbates disease caused by the human immunodeficiency virus (HIV). HIV infected individuals are prone to lung infections by a variety of microbial pathogens, including M. tuberculosis. While the destruction of the adaptive immune response by HIV is well understood, the actual pathogenesis of tuberculosis in co-infected individuals remains unclear. Tat is an HIV protein essential for efficient viral gene transcription, is secreted from infected cells, and is known to influence a variety of host inflammatory responses. We hypothesize Tat contributes to pathophysiological changes in the lung microenvironment, resulting in impaired host immune responses to infection by M. tuberculosis. RESULTS: Herein, we show transgenic mice that express Tat by lung alveolar cells are more susceptible than non-transgenic control littermates to a low-dose aerosol infection of M. tuberculosis W-Beijing SA161. Survival assays demonstrate accelerated mortality rates of the Tat transgenic mice compared to non-transgenics. Tat transgenic mice also showed poorly organized lung granulomata-like lesions. Analysis of the host immune response using quantitative RT-PCR, flow cytometry for surface markers, and intracellular cytokine staining showed increased expression of pro-inflammatory cytokines in the lungs, increased numbers of cells expressing ICAM1, increased numbers of CD4+CD25+Foxp3+ T regulatory cells, and IL-4 producing CD4+ T cells in the Tat transgenics compared to infected non-tg mice. CONCLUSIONS: Our data show quantitative differences in the inflammatory response to the SA161 clinical isolate of M. tuberculosis W-Beijing between Tat transgenic and non-transgenic mice, suggesting Tat contributes to the pathogenesis of tuberculosis. PMID- 22046212 TI - Financial burden of household out-of-pocket expenditures for prescription drugs: cross-sectional analysis based on national survey data. AB - BACKGROUND: Commentaries on the adequacy of insurance coverage for prescription drugs available to Canadians have emphasized differences in the coverage provided by different provincial governments. Less is known about the actual financial burden of prescription drug spending and how this burden varies by province of residence, affluence and source of primary drug coverage. METHODS: We used data from a nationally representative household expenditure survey to analyze the financial burden of prescription drugs. We focused on the drug budget share (defined as the share of the household budget spent on prescription drugs), considering how it varied by province, total household budget and likely primary source of drug insurance coverage (i.e., provincial government plan for senior citizens, social assistance plan or private coverage). We examined both "typical" households (at the median of the distribution of the drug budget share) and households with relatively large shares (in the top 5%). Finally, we estimated the percentage of households with catastrophic drug expenditures (defined as a drug budget share of 10% or more) and the average catastrophic drug expenditures. RESULTS: Senior, social assistance and general population households accounted for 21.1%, 8.9% and 69.9% of the sample of 14,430 respondents to the 2006 Survey of Household Spending, respectively. The median drug budget share in Canada was 1.1% for senior households (range 0.4% [Ontario] to 3.6% [Saskatchewan]) and 0.1% for both social assistance households and general population households, with little appreciable variation across provinces for these latter 2 categories. The 95th percentile drug budget share in Canada was 7.4% for senior households (range 3.5% [Ontario] to 12.7% [Saskatchewan]), 5.4% for social assistance households (range 2.3% [British Columbia] to 13.0% [Prince Edward Island]) and 2.6% for general population households (range 2.1% [Ontario] to 5.4% [Prince Edward Island]). The interprovincial range of the 95th percentile drug budget share was 10.7 percentage points for social assistance households, 9.2 percentage points for senior households and 3.3 percentage points for general population households. INTERPRETATION: For most households, the financial burden of prescription drug expenditures appeared to be relatively small, with little interprovincial variation. However, a small number of households incurred catastrophic drug costs. These households were concentrated in the groups that traditionally benefit from provincial government drug plans. It is likely that some households did not purchase needed prescription drugs because of the expense, so our estimates of the financial burden of catastrophic prescription drug expenditures therefore represent a lower bound. PMID- 22046213 TI - Access to health care of persons with disabilities as an indicator of equity in health systems. PMID- 22046214 TI - Trends in opioid use and dosing among socio-economically disadvantaged patients. AB - BACKGROUND: Opioid therapy for patients with chronic nonmalignant pain remains controversial, primarily because of safety concerns and the potential for abuse. The objective of this study was to examine trends in opioid utilization for nonmalignant pain among recipients of social assistance and to explore the relation between dose of analgesic and mortality. METHODS: Using a cross sectional study design, we characterized annual trends in prescriptions for and daily dose of opioid analgesics between 2003 and 2008 for beneficiaries (aged 15 to 64 years) of Ontario's public drug plan. We defined moderate, high and very high dose thresholds as daily doses of up to 200, 201 to 400, and more than 400 mg oral morphine (or equivalent), respectively. In an exploratory cohort study, we followed, over a 2-year period, patients who received at least one prescription for an opioid in 2004 to investigate the relation between opioid dose and opioid-related mortality. RESULTS: Over the study period, opioid prescribing rates rose by 16.2%, and 180 974 individuals received nearly 1.5 million opioid prescriptions in 2008. Also by 2008, the daily dose dispensed exceeded 200 mg morphine equivalent for almost a third (32.6%) of recipients of long-acting oxycodone but only 20.3% of those treated with fentanyl or other long acting opioids. Among patients for whom high or very high doses of opioids were dispensed in 2004, 19.3% of deaths during the subsequent 2 years were opioid related, occurring at a median age of 46 years. Two-year opioid-related mortality rates were 1.63 per 1000 population (95% confidence interval [CI] 1.42-1.85) among people with moderate-dose prescriptions, 7.92 per 1000 population (95% CI 5.25-11.49) among those with high-dose prescriptions, and 9.94 per 1000 population (95% CI 2.78-25.12) among those with very-high-dose prescriptions. INTERPRETATION: Among socio-economically disadvantaged patients in Ontario, the use and dose of opioids for nonmalignant pain has increased substantially, driven primarily by the use of long-acting oxycodone and, to a lesser extent, fentanyl. The findings of our exploratory study suggested a strong association between opioid-related mortality and the dose of opioid dispensed. PMID- 22046215 TI - Who should travel in kidney exchange programs: the donor, or the organ? PMID- 22046216 TI - Freedom to be altruistic: allowing for risk/knowledge ratios in decisions concerning multiple sclerosis research. PMID- 22046217 TI - Academic Alternate Relationship Plans for internal medicine: a lever for health care transformation. PMID- 22046218 TI - Changes in labelling for metformin use in patients with type 2 diabetes and heart failure: documented safety outweighs theoretical risks. PMID- 22046219 TI - Second-line therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a systematic review and mixed-treatment comparison meta analysis. AB - BACKGROUND: Although there is general agreement that metformin should be used as first-line pharmacotherapy in patients with type 2 diabetes, uncertainty remains regarding the choice of second-line therapy once metformin is no longer effective. We conducted a systematic review and meta-analysis to assess the comparative safety and efficacy of all available classes of antihyperglycemic therapies in patients with type 2 diabetes inadequately controlled on metformin monotherapy. METHODS: MEDLINE, EMBASE, BIOSIS Previews, PubMed and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published in English from 1980 to October 2009. Additional citations were obtained from grey literature and conference proceedings and through stakeholder feedback. Two reviewers independently selected studies, extracted data and assessed risk of bias. Key outcomes of interest were hemoglobin A1c, body weight, hypoglycemia, quality of life, long-term diabetes-related complications, serious adverse drug events and mortality. Mixed-treatment comparison and pairwise meta analyses were conducted to pool trial results, when appropriate. RESULTS: We identified 49 active and non-active controlled randomized trials that compared 2 or more of the following classes of antihyperglycemic agents and weight-loss agents: sulfonylureas, meglitinides, thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, insulins, alpha-glucosidase inhibitors, sibutramine and orlistat. All classes of second-line antihyperglycemic therapies achieved clinically meaningful reductions in hemoglobin A1c (0.6% to 1.0%). No significant differences were found between classes. Insulins and insulin secretagogues were associated with significantly more events of overall hypoglycemia than the other agents, but severe hypoglycemia was rarely observed. An increase in body weight was observed with the majority of second-line therapies (1.8 to 3.0 kg), the exceptions being DPP-4 inhibitors, alpha-glucosidase inhibitors and GLP-1 analogues (0.6 to -1.8 kg). There were insufficient data available for diabetes complications, mortality or quality of life. INTERPRETATION: DPP-4 inhibitors and GLP-1 analogues achieved improvements in glycemic control similar to those of other second-line therapies, although they may have modest benefits in terms of weight gain and overall hypoglycemia. Further long-term trials of adequate power are required to determine whether newer drug classes differ from older agents in terms of clinically meaningful outcomes. PMID- 22046220 TI - Appreciating the medical literature: five notable articles in general internal medicine from 2009 and 2010. PMID- 22046221 TI - The Open Medicine student peer review program. PMID- 22046222 TI - Effect of bodychecking on rate of injuries among minor hockey players. AB - BACKGROUND: Bodychecking is a leading cause of injury among minor hockey players. Its value has been the subject of heated debate since Hockey Canada introduced bodychecking for competitive players as young as 9 years in the 1998/1999 season. Our goal was to determine whether lowering the legal age of bodychecking from 11 to 9 years affected the numbers of all hockey-related injuries and of those specifically related to bodychecking among minor hockey players in Ontario. METHODS: In this retrospective study, we evaluated data collected through the Canadian Hospitals Injury Reporting and Prevention Program. The study's participants were male hockey league players aged 6-17 years who visited the emergency departments of 5 hospitals in Ontario for hockey-related injuries during 10 hockey seasons (September 1994 to May 2004). Injuries were classified as bodychecking-related or non-bodychecking-related. Injuries that occurred after the rule change took effect were compared with those that occurred before the rule's introduction. RESULTS: During the study period, a total of 8552 hockey related injuries were reported, 4460 (52.2%) of which were attributable to bodychecking. The odds ratio (OR) of a visit to the emergency department because of a bodychecking-related injury increased after the rule change (OR 1.26, 95% confidence interval [CI] 1.16-1.38), the head and neck (OR 1.52, 95% CI 1.26 1.84) and the shoulder and arm (OR 1.18, 95% CI 1.04-1.35) being the body parts with the most substantial increases in injury rate. The OR of an emergency visit because of concussion increased significantly in the Atom division after the rule change, which allowed bodychecking in the Atom division. After the rule change, the odds of a bodychecking-related injury was significantly higher in the Atom division (OR 2.20, 95% CI 1.70-2.84). INTERPRETATION: In this study, the odds of injury increased with decreasing age of exposure to bodychecking. These findings add to the growing evidence that bodychecking holds greater risk than benefit for youth and support widespread calls to ban this practice. PMID- 22046223 TI - Open Medicine endorses PROSPERO. PMID- 22046225 TI - Prisons and public health. PMID- 22046224 TI - Social determinants of health associated with hepatitis C co-infection among people living with HIV: results from the Positive Spaces, Healthy Places study. AB - BACKGROUND: Social determinants of health (SDOH) may influence the probability of people living with HIV also being infected with hepatitis C virus (HCV). We compared the SDOH of adults co-infected with HCV/HIV with that of HIV mono infected adults to identify factors independently associated with HCV infection. METHODS: In this cross-sectional study, face-to-face interviews were conducted with 509 HIV-infected adults affiliated with or receiving services from community based AIDS service organizations (CBAOs). The primary outcome measure was self reported HCV infection status. Chi-square, Student's t tests, and Wilcoxon rank sum tests were performed to compare SDOH of HCV/HIV co-infected participants with that of HIV mono-infected participants. Multivariable hierarchical logistic regression was used to identify factors independently associated with HCV co infection. RESULTS: Data on 482 (95 HCV/HIV co-infected and 387 HIV mono infected) adults were analyzed. Compared with participants infected with HIV only, those who were co-infected with HIV and HCV were more likely to be heterosexual, Aboriginal, less educated and unemployed. They were more likely to have a low income, to not be receiving antiretroviral treatment, to live outside the Greater Toronto Area (GTA), to use/abuse substances, experience significant depression, and utilize addiction counselling and needle-exchange services. They also were more likely to report a history of homelessness and perceived housing related discrimination and to have moved twice or more in the previous 12 months. Factors independently associated with HCV/HIV co-infection were history of incarceration (odds ratio [OR] 8.81, 95% CI 4.43-17.54), history of homelessness (OR 3.15, 95% CI 1.59-6.26), living outside of the GTA (OR 3.13, 95% CI 1.59 6.15), and using/abusing substances in the past 12 months (OR 2.05, 95% CI 1.07 3.91). CONCLUSION: Differences in SDOH exist between HIV/HCV co-infected and HIV mono-infected adults. History of incarceration, history of homelessness, substance use, and living outside the GTA were independently associated with HCV/HIV co-infection. Interventions that reduce homelessness and incarceration may help prevent HCV infection in people living with HIV. PMID- 22046226 TI - Frank words about breast screening. PMID- 22046227 TI - Personal music players and hearing loss: are we deaf to the risks? PMID- 22046228 TI - What do we know about Canadian involvement in medical tourism?: a scoping review. AB - BACKGROUND: Medical tourism, the intentional pursuit of elective medical treatments in foreign countries, is a rapidly growing global industry. Canadians are among those crossing international borders to seek out privately purchased medical care. Given Canada's universally accessible, single-payer domestic health care system, important implications emerge from Canadians' private engagement in medical tourism. METHODS: A scoping review was conducted of the popular, academic, and business literature to synthesize what is currently known about Canadian involvement in medical tourism. Of the 348 sources that were reviewed either partly or in full, 113 were ultimately included in the review. RESULTS: The review demonstrates that there is an extreme paucity of academic, empirical literature examining medical tourism in general or the Canadian context more specifically. Canadians are engaged with the medical tourism industry not just as patients but also as investors and business people. There have been a limited number of instances of Canadians having their medical tourism expenses reimbursed by the public medicare system. Wait times are by far the most heavily cited driver of Canadians' involvement in medical tourism. However, despite its treatment as fact, there is no empirical research to support or contradict this point. DISCUSSION: Although medical tourism is often discussed in the Canadian context, a paucity of data on this practice complicates our understanding of its scope and impact. PMID- 22046229 TI - Ontario's plunging price-caps on generics: deeper dives may drown some drugs. AB - In April 2010, the Ontario government announced another reduction in the maximum price of generic drugs permitted under the Ontario Drug Benefit (ODB) program, demanding that generic drugs now be sold for no more than 25% of the branded product's price. Other provinces are following Ontario in setting unprecedentedly low price-caps to reduce the cost of generic drugs. Generic product substitution legislation is vital to reducing costs to provincial drug plans, yet lower and lower price-caps may undo some of the benefits of substitution legislation if generics find it difficult to survive. PMID- 22046230 TI - Repeated assessments of informed consent comprehension among HIV-infected participants of a three-year clinical trial in Botswana. AB - BACKGROUND: Informed consent (IC) has been an international standard for decades for the ethical conduct of clinical trials. Yet frequently study participants have incomplete understanding of key issues, a problem exacerbated by language barriers or lack of familiarity with research concepts. Few investigators measure participant comprehension of IC, while even fewer conduct interim assessments once a trial is underway. METHODS AND FINDINGS: We assessed comprehension of IC using a 20-question true/false quiz administered in 6-month intervals in the context of a placebo-controlled, randomized trial for the prevention of tuberculosis among HIV-infected adults in Botswana (2004-2009). Quizzes were offered in both Setswana and English. To enroll in the TB trial, participants were required to have >= 16/20 correct responses. We examined concepts understood and the degree to which understanding changed over three-years. We analyzed 5,555 quizzes from 1,835 participants. The participants' highest education levels were: 28% primary, 59% secondary, 9% tertiary and 7% no formal education. Eighty percent of participants passed the enrollment quiz (Quiz1) on their first attempt and the remainder passed on their second attempt. Those having higher than primary education and those who took the quiz in English were more likely to receive a passing score on their first attempt (adjusted odds ratios and 95% confidence intervals, 3.1 (2.4-4.0) and 1.5 (1.2, 1.9), respectively). The trial's purpose or procedures were understood by 90-100% of participants, while 44-77% understood randomization, placebos, or risks. Participants who failed Quiz1 on their initial attempt were more likely to fail quizzes later in the trial. Pass rates improved with quiz re-administration in subsequent years. CONCLUSIONS: Administration of a comprehension quiz at enrollment and during follow-up was feasible in a large, international collaboration and efficiently determined IC comprehension by trial participants. Strategies to improve understanding of concepts like placebos and randomization are needed. Comprehension assessments throughout a study may reinforce key concepts. PMID- 22046231 TI - Penicillin binding proteins as danger signals: meningococcal penicillin binding protein 2 activates dendritic cells through Toll-like receptor 4. AB - Neisseria meningitidis is a human pathogen responsible for life-threatening inflammatory diseases. Meningococcal penicillin-binding proteins (PBPs) and particularly PBP2 are involved in bacterial resistance to beta-lactams. Here we describe a novel function for PBP2 that activates human and mouse dendritic cells (DC) in a time and dose-dependent manner. PBP2 induces MHC II (LOGEC50 = 4.7 ug/ml +/- 0.1), CD80 (LOGEC50 = 4.88 ug/ml +/- 0.15) and CD86 (LOGEC50 = 5.36 ug/ml +/- 0.1). This effect was abolished when DCs were co-treated with anti-PBP2 antibodies. PBP2-treated DCs displayed enhanced immunogenic properties in vitro and in vivo. Furthermore, proteins co-purified with PBP2 showed no effect on DC maturation. We show through different in vivo and in vitro approaches that this effect is not due to endotoxin contamination. At the mechanistic level, PBP2 induces nuclear localization of p65 NF-kB of 70.7 +/- 5.1% cells versus 12 +/- 2.6% in untreated DCs and needs TLR4 expression to mature DCs. Immunoprecipitation and blocking experiments showed thatPBP2 binds TLR4. In conclusion, we describe a novel function of meningococcal PBP2 as a pathogen associated molecular pattern (PAMP) at the host-pathogen interface that could be recognized by the immune system as a danger signal, promoting the development of immune responses. PMID- 22046232 TI - Improving ECG classification accuracy using an ensemble of neural network modules. AB - This paper illustrates the use of a combined neural network model based on Stacked Generalization method for classification of electrocardiogram (ECG) beats. In conventional Stacked Generalization method, the combiner learns to map the base classifiers' outputs to the target data. We claim adding the input pattern to the base classifiers' outputs helps the combiner to obtain knowledge about the input space and as the result, performs better on the same task. Experimental results support our claim that the additional knowledge according to the input space, improves the performance of the proposed method which is called Modified Stacked Generalization. In particular, for classification of 14966 ECG beats that were not previously seen during training phase, the Modified Stacked Generalization method reduced the error rate for 12.41% in comparison with the best of ten popular classifier fusion methods including Max, Min, Average, Product, Majority Voting, Borda Count, Decision Templates, Weighted Averaging based on Particle Swarm Optimization and Stacked Generalization. PMID- 22046233 TI - Impact of genetic variation in SORCS1 on memory retention. AB - OBJECTIVE: We previously reported that genetic variants in SORCS1 increase the risk of AD, that over-expression of SorCS1 reduces gamma-secretase activity and Abeta levels, and that SorCS1 suppression increases gamma-secretase processing of APP and Abeta levels. We now explored the effect of variation in SORCS1 on memory. METHODS: We explored associations between SORCS1-SNPs and memory retention in the NIA-LOAD case control dataset (162 cases,670 controls) and a cohort of Caribbean Hispanics (549 cases,544 controls) using single marker and haplotype analyses. RESULTS: Three SNPs in intron 1, were associated with memory retention in the NIA-LOAD dataset or the Caribbean Hispanic dataset (rs10884402(A allele:beta = -0.15,p = 0.008), rs7078098(C allele:beta = 0.18,p = 0.007) and rs950809(C allele:beta = 0.17,p = 0.008)) and all three SNPs were significant in a meta-analysis of both datasets (0.002500 nm), drive fast visual processes, which are largely blind to chromatic signals from more narrowly-tuned photoreceptors with peak sensitivities in the blue and UV regions of the spectrum. In addition, electrophysiological properties of the photoreceptor membrane may result in differences in response dynamics of photoreceptors of similar spectral class between species, and different spectral classes within a species. We used intracellular electrophysiological techniques to investigate response dynamics of the three spectral classes of photoreceptor underlying trichromatic colour vision in the bumblebee, Bombus impatiens, and we compare these with previously published data from a related species, Bombus terrestris. In both species, we found significantly faster responses in green, compared with blue- or UV-sensitive photoreceptors, although all 3 photoreceptor types are slower in B. impatiens than in B. terrestris. Integration times for light-adapted B. impatiens photoreceptors (estimated from impulse response half width) were 11.3 +/- 1.6 ms for green photoreceptors compared with 18.6 +/- 4.4 ms and 15.6 +/- 4.4 for blue and UV, respectively. We also measured photoreceptor input resistance in dark- and light-adapted conditions. All photoreceptors showed a decrease in input resistance during light adaptation, but this decrease was considerably larger (declining to about 22% of the dark value) in green photoreceptors, compared to blue and UV (41% and 49%, respectively). Our results suggest that the conductances associated with light adaptation are largest in green photoreceptors, contributing to their greater temporal processing speed. We suggest that the faster temporal processing of green photoreceptors is related to their role in driving fast achromatic visual processes. PMID- 22046252 TI - The network of global corporate control. AB - The structure of the control network of transnational corporations affects global market competition and financial stability. So far, only small national samples were studied and there was no appropriate methodology to assess control globally. We present the first investigation of the architecture of the international ownership network, along with the computation of the control held by each global player. We find that transnational corporations form a giant bow-tie structure and that a large portion of control flows to a small tightly-knit core of financial institutions. This core can be seen as an economic "super-entity" that raises new important issues both for researchers and policy makers. PMID- 22046253 TI - Chromatin immunoprecipitation (ChIP): revisiting the efficacy of sample preparation, sonication, quantification of sheared DNA, and analysis via PCR. AB - The "quantitative" ChIP, a tool commonly used to study protein-DNA interactions in cells and tissue, is a difficult assay often plagued with technical error. We present, herein, the process required to merge multiple protocols into a quick, reliable and easy method and an approach to accurately quantify ChIP DNA prior to performing PCR. We demonstrate that high intensity sonication for at least 30 min is required for full cellular disruption and maximum DNA recovery because ChIP lysis buffers fail to lyse formaldehyde-fixed cells. In addition, extracting ChIP DNA with chelex-100 yields samples that are too dilute for evaluation of shearing efficiency or quantification via nanospectrophotometry. However, DNA extracted from the Mock-ChIP supernatant via the phenol-chloroform-isoamyl alcohol (PCIA) method can be used to evaluate DNA shearing efficiency and used as the standard in a fluorescence-based microplate assay. This enabled accurate quantification of DNA in chelex-extracted ChIP samples and normalization to total DNA concentration prior to performing real-time PCR (rtPCR). Thus, a quick ChIP assay that can be completed in nine bench hours over two days has been validated along with a rapid, accurate and repeatable way to quantify ChIP DNA. The resulting rtPCR data more accurately depicts treatment effects on protein-DNA interactions of interest. PMID- 22046254 TI - Growth of Acinetobacter baumannii in pellicle enhanced the expression of potential virulence factors. AB - BACKGROUND: Interestingly, Acinetobacter baumannii presents an enhanced capacity to form biofilms (also named pellicles) at the air-liquid interface as compared to the other Acinetobacter species. This characteristic questions the contribution of this phenotype to an increased risk of clinical infections by this pathogen. METHODOLOGY/PRINCIPAL FINDINGS: By a proteomic approach using 2-D gel electrophoresis-LC-MS/MS mass spectrometry, we compared the membrane protein patterns of A. baumannii 77, a pellicle-forming clinical isolate, grown in planktonic and in sessile modes. We identified 52 proteins with a differential expression, including 32 up-regulated and 20 down-regulated in the pellicle state. Several proteins, differentially expressed during pellicle development, were of particular interest. We determined the over-expression of four siderophore iron uptake systems including the acinetobactin and enterobactin receptors and confirmed that the development of this type of biofilm is promoted by ferric ions. Two over-expressed proteins, CarO and an OprD-homologue, putative carbapenem-resistance associated porins, would be involved in the transport of specific compounds, like ornithine, a biosynthesis precursor of a siderophore from the hydroxamate family. We evidenced the overexpression of a lipase and a transporter of LCFA that may be involved in the recycling of lipids inside the pellicle matrix. Finally, we demonstrated both by proteomic and by AFM studies that this particular type of biofilm required multiple pili systems to maintain this cohesive structure at the air-liquid interface; two of these systems have never been described in A. baumannii. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated that several proteins, overexpressed at a late state of pellicle development, could be potentially involved in virulence processes. Therefore, regarding the number of potential virulence factors that are over-expressed in this growth mode, the pellicle-forming clinical isolates should be kept under survey. PMID- 22046255 TI - Cost-effectiveness of pharmacotherapy to reduce obesity. AB - AIMS: Obesity causes a high disease burden in Australia and across the world. We aimed to analyse the cost-effectiveness of weight reduction with pharmacotherapy in Australia, and to assess its potential to reduce the disease burden due to excess body weight. METHODS: We constructed a multi-state life-table based Markov model in Excel in which body weight influences the incidence of stroke, ischemic heart disease, hypertensive heart disease, diabetes mellitus, osteoarthritis, post-menopausal breast cancer, colon cancer, endometrial cancer and kidney cancer. We use data on effectiveness identified from PubMed searches, on mortality from Australian Bureau of Statistics, on disease costs from the Australian Institute of Health and Welfare, and on drug costs from the Department of Health and Ageing. We evaluate 1-year pharmacological interventions with sibutramine and orlistat targeting obese Australian adults free of obesity related disease. We use a lifetime horizon for costs and health outcomes and a health sector perspective for costs. Incremental Cost-Effectiveness Ratios (ICERs) below A$50 000 per Disability Adjusted Life Year (DALY) averted are considered good value for money. RESULTS: The ICERs are A$130 000/DALY (95% uncertainty interval [UI] 93 000-180 000) for sibutramine and A$230 000/DALY (170 000-340 000) for orlistat. The interventions reduce the body weight-related disease burden at the population level by 0.2% and 0.1%, respectively. Modest weight loss during the interventions, rapid post-intervention weight regain and low adherence limit the health benefits. CONCLUSIONS: Treatment with sibutramine or orlistat is not cost-effective from an Australian health sector perspective and has a negligible impact on the total body weight-related disease burden. PMID- 22046256 TI - VDA, a method of choosing a better algorithm with fewer validations. AB - The multitude of bioinformatics algorithms designed for performing a particular computational task presents end-users with the problem of selecting the most appropriate computational tool for analyzing their biological data. The choice of the best available method is often based on expensive experimental validation of the results. We propose an approach to design validation sets for method comparison and performance assessment that are effective in terms of cost and discrimination power.Validation Discriminant Analysis (VDA) is a method for designing a minimal validation dataset to allow reliable comparisons between the performances of different algorithms. Implementation of our VDA approach achieves this reduction by selecting predictions that maximize the minimum Hamming distance between algorithmic predictions in the validation set. We show that VDA can be used to correctly rank algorithms according to their performances. These results are further supported by simulations and by realistic algorithmic comparisons in silico.VDA is a novel, cost-efficient method for minimizing the number of validation experiments necessary for reliable performance estimation and fair comparison between algorithms.Our VDA software is available at http://sourceforge.net/projects/klugerlab/files/VDA/ PMID- 22046257 TI - Treatment of rat spinal cord injury with the neurotrophic factor albumin-oleic acid: translational application for paralysis, spasticity and pain. AB - Sensorimotor dysfunction following incomplete spinal cord injury (iSCI) is often characterized by the debilitating symptoms of paralysis, spasticity and pain, which require treatment with novel pleiotropic pharmacological agents. Previous in vitro studies suggest that Albumin (Alb) and Oleic Acid (OA) may play a role together as an endogenous neurotrophic factor. Although Alb can promote basic recovery of motor function after iSCI, the therapeutic effect of OA or Alb-OA on a known translational measure of SCI associated with symptoms of spasticity and change in nociception has not been studied. Following T9 spinal contusion injury in Wistar rats, intrathecal treatment with: i) Saline, ii) Alb (0.4 nanomoles), iii) OA (80 nanomoles), iv) Alb-Elaidic acid (0.4/80 nanomoles), or v) Alb-OA (0.4/80 nanomoles) were evaluated on basic motor function, temporal summation of noxious reflex activity, and with a new test of descending modulation of spinal activity below the SCI up to one month after injury. Albumin, OA and Alb-OA treatment inhibited nociceptive Tibialis Anterior (TA) reflex activity. Moreover Alb-OA synergistically promoted early recovery of locomotor activity to 50 +/- 10% of control and promoted de novo phasic descending inhibition of TA noxious reflex activity to 47 +/- 5% following non-invasive electrical conditioning stimulation applied above the iSCI. Spinal L4-L5 immunohistochemistry demonstrated a unique increase in serotonin fibre innervation up to 4.2 +/- 1.1 and 2.3 +/- 0.3 fold within the dorsal and ventral horn respectively with Alb-OA treatment when compared to uninjured tissue, in addition to a reduction in NR1 NMDA receptor phosphorylation and microglia reactivity. Early recovery of voluntary motor function accompanied with tonic and de novo phasic descending inhibition of nociceptive TA flexor reflex activity following Alb-OA treatment, mediated via known endogenous spinal mechanisms of action, suggests a clinical application of this novel neurotrophic factor for the treatment of paralysis, spasticity and pain. PMID- 22046258 TI - Genetic associations in the vitamin D receptor and colorectal cancer in African Americans and Caucasians. AB - Low vitamin D levels are associated with an increased incidence of colorectal cancer (CRC) and higher mortality from the disease. In the US, African Americans (AAs) have the highest CRC incidence and mortality and the lowest levels of vitamin D. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been previously associated with CRC, but few studies have included AAs. We studied 795 AA CRC cases and 985 AA controls from Chicago and North Carolina as well as 1324 Caucasian cases and 990 Caucasian controls from Chicago and Spain. We genotyped 54 tagSNPs in VDR (46586959 to 46521297 Mb) and tested for association adjusting for West African ancestry, age, gender, and multiple testing. Untyped markers were imputed using MACH1.0. We analyzed associations by gender and anatomic location in the whole study group as well as by vitamin D intake in the North Carolina AA group. In the joint analysis, none of the SNPs tested was significantly associated with CRC. For four previously tested restriction fragment length polymorphisms, only one (referred to as ApaI), tagged by the SNP rs79628898, had a nominally significant p-value in AAs; none of these polymorphisms were associated with CRC in Caucasians. In the North Carolina AAs, for whom we had vitamin D intake data, we found a significant association between an intronic SNP rs11574041 and vitamin D intake, which is evidence for a VDR gene environment interaction in AAs. In summary, using a systematic tagSNP approach, we have not found evidence for significant associations between VDR and CRC in AAs or Caucasians. PMID- 22046259 TI - Comprehensive network analysis of anther-expressed genes in rice by the combination of 33 laser microdissection and 143 spatiotemporal microarrays. AB - Co-expression networks systematically constructed from large-scale transcriptome data reflect the interactions and functions of genes with similar expression patterns and are a powerful tool for the comprehensive understanding of biological events and mining of novel genes. In Arabidopsis (a model dicot plant), high-resolution co-expression networks have been constructed from very large microarray datasets and these are publicly available as online information resources. However, the available transcriptome data of rice (a model monocot plant) have been limited so far, making it difficult for rice researchers to achieve reliable co-expression analysis. In this study, we performed co expression network analysis by using combined 44 K agilent microarray datasets of rice, which consisted of 33 laser microdissection (LM)-microarray datasets of anthers, and 143 spatiotemporal transcriptome datasets deposited in RicexPro. The entire data of the rice co-expression network, which was generated from the 176 microarray datasets by the Pearson correlation coefficient (PCC) method with the mutual rank (MR)-based cut-off, contained 24,258 genes and 60,441 genes pairs. Using these datasets, we constructed high-resolution co-expression subnetworks of two specific biological events in the anther, "meiosis" and "pollen wall synthesis". The meiosis network contained many known or putative meiotic genes, including genes related to meiosis initiation and recombination. In the pollen wall synthesis network, several candidate genes involved in the sporopollenin biosynthesis pathway were efficiently identified. Hence, these two subnetworks are important demonstrations of the efficiency of co-expression network analysis in rice. Our co-expression analysis included the separated transcriptomes of pollen and tapetum cells in the anther, which are able to provide precise information on transcriptional regulation during male gametophyte development in rice. The co-expression network data presented here is a useful resource for rice researchers to elucidate important and complex biological events. PMID- 22046260 TI - Altered expression of insulin receptor isoforms in breast cancer. AB - PURPOSE: Insulin-like growth factor (IGF) signaling through human insulin receptor isoform A (IR-A) contributes to tumorigenesis and intrinsic resistance to anti-IGF1R therapy. In the present study, we (a) developed quantitative TaqMan real time-PCR-based assays (qRT-PCR) to measure human insulin receptor isoforms with high specificity, (b) evaluated isoform expression levels in molecularly defined breast cancer subtypes, and (c) identified the IR-A:IR-B mRNA ratio as a potential biomarker guiding patient stratification for anti-IGF therapies. EXPERIMENTAL DESIGN: mRNA expression levels of IR-A and IR-B were measured in 42 primary breast cancers and 19 matched adjacent normal tissues with TaqMan qRT-PCR assays. The results were further confirmed in 165 breast cancers. The tumor samples were profiled using whole genome microarrays and subsequently subtyped using the PAM50 breast cancer gene signature. The relationship between the IR A:IR-B ratio and cancer subtype, as well as markers of proliferation were characterized. RESULTS: The mRNA expression levels of IR-A in the breast tumors were similar to those observed in the adjacent normal tissues, while the mRNA levels of IR-B were significantly decreased in tumors. The IR-A:IR-B ratio was significantly higher in luminal B breast cancer than in luminal A. Strong concordance between the IR-A:IR-B ratio and the composite Oncotype DX proliferation score was observed for stratifying the latter two breast cancer subtypes. CONCLUSIONS: The reduction in IR-B expression is the key to the altered IR-A:IR-B ratio observed in breast cancer. The IR-A:IR-B ratio may have biomarker utility in guiding a patient stratification strategy for an anti-IGF therapeutic. PMID- 22046261 TI - Mastermind mutations generate a unique constellation of midline cells within the Drosophila CNS. AB - BACKGROUND: The Notch pathway functions repeatedly during the development of the central nervous system in metazoan organisms to control cell fate and regulate cell proliferation and asymmetric cell divisions. Within the Drosophila midline cell lineage, which bisects the two symmetrical halves of the central nervous system, Notch is required for initial cell specification and subsequent differentiation of many midline lineages. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide the first description of the role of the Notch co-factor, mastermind, in the central nervous system midline of Drosophila. Overall, zygotic mastermind mutations cause an increase in midline cell number and decrease in midline cell diversity. Compared to mutations in other components of the Notch signaling pathway, such as Notch itself and Delta, zygotic mutations in mastermind cause the production of a unique constellation of midline cell types. The major difference is that midline glia form normally in zygotic mastermind mutants, but not in Notch and Delta mutants. Moreover, during late embryogenesis, extra anterior midline glia survive in zygotic mastermind mutants compared to wild type embryos. CONCLUSIONS/SIGNIFICANCE: This is an example of a mutation in a signaling pathway cofactor producing a distinct central nervous system phenotype compared to mutations in major components of the pathway. PMID- 22046262 TI - dTip60 HAT activity controls synaptic bouton expansion at the Drosophila neuromuscular junction. AB - BACKGROUND: Histone acetylation of chromatin plays a key role in promoting the dynamic transcriptional responses in neurons that influence the neuroplasticity linked to cognitive ability, yet the specific histone acetyltransferases (HATs) that create such epigenetic marks remain to be elucidated. METHODS AND FINDINGS: Here we use the Drosophila neuromuscular junction (NMJ) as a well-characterized synapse model to identify HATs that control synaptic remodeling and structure. We show that the HAT dTip60 is concentrated both pre and post-synaptically within the NMJ. Presynaptic targeted reduction of dTip60 HAT activity causes a significant increase in synaptic bouton number that specifically affects type Is boutons. The excess boutons show a suppression of the active zone synaptic function marker bruchpilot, suggesting defects in neurotransmission function. Analysis of microtubule organization within these excess boutons using immunohistochemical staining to the microtubule associated protein futsch reveals a significant increase in the rearrangement of microtubule loop architecture that is required for bouton division. Moreover, alpha-tubulin acetylation levels of microtubules specifically extending into the terminal synaptic boutons are reduced in response to dTip60 HAT reduction. CONCLUSIONS: Our results are the first to demonstrate a causative role for the HAT dTip60 in the control of synaptic plasticity that is achieved, at least in part, via regulation of the synaptic microtubule cytoskeleton. These findings have implications for dTip60 HAT dependant epigenetic mechanisms underlying cognitive function. PMID- 22046263 TI - Ectodermal influx and cell hypertrophy provide early growth for all murine mammary rudiments, and are differentially regulated among them by Gli3. AB - Mammary gland development starts in utero with one or several pairs of mammary rudiments (MRs) budding from the surface ectodermal component of the mammalian embryonic skin. Mice develop five pairs, numbered MR1 to MR5 from pectoral to inguinal position. We have previously shown that Gli3(Xt-J/Xt-J) mutant embryos, which lack the transcription factor Gli3, do not form MR3 and MR5. We show here that two days after the MRs emerge, Gli3(Xt-J/Xt-J) MR1 is 20% smaller, and Gli3(Xt-J/Xt-J) MR2 and MR4 are 50% smaller than their wild type (wt) counterparts. Moreover, while wt MRs sink into the underlying dermis, Gli3(Xt J/Xt-J) MR4 and MR2 protrude outwardly, to different extents. To understand why each of these five pairs of functionally identical organs has its own, distinct response to the absence of Gli3, we determined which cellular mechanisms regulate growth of the individual MRs, and whether and how Gli3 regulates these mechanisms. We found a 5.5 to 10.7-fold lower cell proliferation rate in wt MRs compared to their adjacent surface ectoderm, indicating that MRs do not emerge or grow via locally enhanced cell proliferation. Cell-tracing experiments showed that surface ectodermal cells are recruited toward the positions where MRs emerge, and contribute to MR growth during at least two days. During the second day of MR development, peripheral cells within the MRs undergo hypertrophy, which also contributes to MR growth. Limited apoptotic cell death counterbalances MR growth. The relative contribution of each of these processes varies among the five MRs. Furthermore, each of these processes is impaired in the absence of Gli3, but to different extents in each MR. This differential involvement of Gli3 explains the variation in phenotype among Gli3(Xt-J/Xt-J) MRs, and may help to understand the variation in numbers and positions of mammary glands among mammals. PMID- 22046264 TI - Elucidation of the ATP7B N-domain Mg2+-ATP coordination site and its allosteric regulation. AB - The diagnostic of orphan genetic disease is often a puzzling task as less attention is paid to the elucidation of the pathophysiology of these rare disorders at the molecular level. We present here a multidisciplinary approach using molecular modeling tools and surface plasmonic resonance to study the function of the ATP7B protein, which is impaired in the Wilson disease. Experimentally validated in silico models allow the elucidation in the Nucleotide binding domain (N-domain) of the Mg(2+)-ATP coordination site and answer to the controversial role of the Mg(2+) ion in the nucleotide binding process. The analysis of protein motions revealed a substantial effect on a long flexible loop branched to the N-domain protein core. We demonstrated the capacity of the loop to disrupt the interaction between Mg(2+)-ATP complex and the N-domain and propose a role for this loop in the allosteric regulation of the nucleotide binding process. PMID- 22046265 TI - Oscillatory dynamics of cell cycle proteins in single yeast cells analyzed by imaging cytometry. AB - Progression through the cell division cycle is orchestrated by a complex network of interacting genes and proteins. Some of these proteins are known to fluctuate periodically during the cell cycle, but a systematic study of the fluctuations of a broad sample of cell-cycle proteins has not been made until now. Using time lapse fluorescence microscopy, we profiled 16 strains of budding yeast, each containing GFP fused to a single gene involved in cell cycle regulation. The dynamics of protein abundance and localization were characterized by extracting the amplitude, period, and other indicators from a series of images. Oscillations of protein abundance could clearly be identified for Cdc15, Clb2, Cln1, Cln2, Mcm1, Net1, Sic1, and Whi5. The period of oscillation of the fluorescently tagged proteins is generally in good agreement with the inter-bud time. The very strong oscillations of Net1 and Mcm1 expression are remarkable since little is known about the temporal expression of these genes. By collecting data from large samples of single cells, we quantified some aspects of cell-to-cell variability due presumably to intrinsic and extrinsic noise affecting the cell cycle. PMID- 22046266 TI - High prevalence of primary multidrug resistant tuberculosis in persons with no known risk factors. AB - INTRODUCTION: In high multidrug resistant (MDR) tuberculosis (TB) prevalence areas, drug susceptibility testing (DST) at diagnosis is recommended for patients with risk factors for MDR. However, this approach might miss a substantial proportion of MDR-TB in the general population. We studied primary MDR in patients considered to be at low risk of MDR-TB in Lima, Peru. METHODS: We enrolled new sputum smear-positive TB patients who did not report any MDR-TB risk factor: known exposure to a TB patient whose treatment failed or who died or who was known to have MDR-TB; immunosuppressive co-morbidities, ex prison inmates; prison and health care workers; and alcohol or drug abuse. A structured questionnaire was applied to all enrolled participants to confirm the absence of these factors and thus minimize underreporting. Sputum from all participants was cultured on Lowenstein-Jensen media and DST for first line drugs was performed using the 7H10 agar method. RESULTS: Of 875 participants with complete data, 23.2% (203) had risk factors for MDR-TB elicited after enrolment. Among the group with no reported risk factors who had a positive culture, we found a 6.3% (95%CI 4.4-8.3) (37/584) rate of MDR-TB. In this group no epidemiological characteristics were associated with MDR-TB. Thus, in this group, multidrug resistance occurred in patients with no identifiable risk factors. CONCLUSIONS: We found a high rate of primary MDR-TB in a general population with no identifiable risk factors for MDR-TB. This suggests that in a high endemic area targeting patients for MDR-TB based on the presence of risk factors is an insufficient intervention. PMID- 22046267 TI - A new methodology to associate SNPs with human diseases according to their pathway related context. AB - Genome-wide association studies (GWAS) with hundreds of zthousands of single nucleotide polymorphisms (SNPs) are popular strategies to reveal the genetic basis of human complex diseases. Despite many successes of GWAS, it is well recognized that new analytical approaches have to be integrated to achieve their full potential. Starting with a list of SNPs, found to be associated with disease in GWAS, here we propose a novel methodology to devise functionally important KEGG pathways through the identification of genes within these pathways, where these genes are obtained from SNP analysis. Our methodology is based on functionalization of important SNPs to identify effected genes and disease related pathways. We have tested our methodology on WTCCC Rheumatoid Arthritis (RA) dataset and identified: i) previously known RA related KEGG pathways (e.g., Toll-like receptor signaling, Jak-STAT signaling, Antigen processing, Leukocyte transendothelial migration and MAPK signaling pathways); ii) additional KEGG pathways (e.g., Pathways in cancer, Neurotrophin signaling, Chemokine signaling pathways) as associated with RA. Furthermore, these newly found pathways included genes which are targets of RA-specific drugs. Even though GWAS analysis identifies 14 out of 83 of those drug target genes; newly found functionally important KEGG pathways led to the discovery of 25 out of 83 genes, known to be used as drug targets for the treatment of RA. Among the previously known pathways, we identified additional genes associated with RA (e.g. Antigen processing and presentation, Tight junction). Importantly, within these pathways, the associations between some of these additionally found genes, such as HLA-C, HLA-G, PRKCQ, PRKCZ, TAP1, TAP2 and RA were verified by either OMIM database or by literature retrieved from the NCBI PubMed module. With the whole-genome sequencing on the horizon, we show that the full potential of GWAS can be achieved by integrating pathway and network-oriented analysis and prior knowledge from functional properties of a SNP. PMID- 22046268 TI - A novel metagenomic short-chain dehydrogenase/reductase attenuates Pseudomonas aeruginosa biofilm formation and virulence on Caenorhabditis elegans. AB - In Pseudomonas aeruginosa, the expression of a number of virulence factors, as well as biofilm formation, are controlled by quorum sensing (QS). N Acylhomoserine lactones (AHLs) are an important class of signaling molecules involved in bacterial QS and in many pathogenic bacteria infection and host colonization are AHL-dependent. The AHL signaling molecules are subject to inactivation mainly by hydrolases (Enzyme Commission class number EC 3) (i.e. N acyl-homoserine lactonases and N-acyl-homoserine-lactone acylases). Only little is known on quorum quenching mechanisms of oxidoreductases (EC 1). Here we report on the identification and structural characterization of the first NADP-dependent short-chain dehydrogenase/reductase (SDR) involved in inactivation of N-(3-oxo dodecanoyl)-L-homoserine lactone (3-oxo-C(12)-HSL) and derived from a metagenome library. The corresponding gene was isolated from a soil metagenome and designated bpiB09. Heterologous expression and crystallographic studies established BpiB09 as an NADP-dependent reductase. Although AHLs are probably not the native substrate of this metagenome-derived enzyme, its expression in P. aeruginosa PAO1 resulted in significantly reduced pyocyanin production, decreased motility, poor biofilm formation and absent paralysis of Caenorhabditis elegans. Furthermore, a genome-wide transcriptome study suggested that the level of lasI and rhlI transcription together with 36 well known QS regulated genes was significantly (>=10-fold) affected in P. aeruginosa strains expressing the bpiB09 gene in pBBR1MCS-5. Thus AHL oxidoreductases could be considered as potent tools for the development of quorum quenching strategies. PMID- 22046269 TI - Cholesterol influences voltage-gated calcium channels and BK-type potassium channels in auditory hair cells. AB - The influence of membrane cholesterol content on a variety of ion channel conductances in numerous cell models has been shown, but studies exploring its role in auditory hair cell physiology are scarce. Recent evidence shows that cholesterol depletion affects outer hair cell electromotility and the voltage gated potassium currents underlying tall hair cell development, but the effects of cholesterol on the major ionic currents governing auditory hair cell excitability are unknown. We investigated the effects of a cholesterol-depleting agent (methyl beta cyclodextrin, MbetaCD) on ion channels necessary for the early stages of sound processing. Large-conductance BK-type potassium channels underlie temporal processing and open in a voltage- and calcium-dependent manner. Voltage gated calcium channels (VGCCs) are responsible for calcium-dependent exocytosis and synaptic transmission to the auditory nerve. Our results demonstrate that cholesterol depletion reduced peak steady-state calcium-sensitive (BK-type) potassium current by 50% in chick cochlear hair cells. In contrast, MbetaCD treatment increased peak inward calcium current (~30%), ruling out loss of calcium channel expression or function as a cause of reduced calcium-sensitive outward current. Changes in maximal conductance indicated a direct impact of cholesterol on channel number or unitary conductance. Immunoblotting following sucrose-gradient ultracentrifugation revealed BK expression in cholesterol enriched microdomains. Both direct impacts of cholesterol on channel biophysics, as well as channel localization in the membrane, may contribute to the influence of cholesterol on hair cell physiology. Our results reveal a new role for cholesterol in the regulation of auditory calcium and calcium-activated potassium channels and add to the growing evidence that cholesterol is a key determinant in auditory physiology. PMID- 22046270 TI - Protein kinase C-dependent dephosphorylation of tyrosine hydroxylase requires the B56delta heterotrimeric form of protein phosphatase 2A. AB - Tyrosine hydroxylase, which plays a critical role in regulation of dopamine synthesis, is known to be controlled by phosphorylation at several critical sites. One of these sites, Ser40, is phosphorylated by a number of protein kinases, including protein kinase A. The major protein phosphatase that dephosphorylates Ser40 is protein phosphatase-2A (PP2A). A recent study has also linked protein kinase C to the dephosphorylation of Ser40 [1], but the mechanism is unclear. PP2A isoforms are comprised of catalytic, scaffold, and regulatory subunits, the regulatory B subunits being able to influence cellular localization and substrate selection. In the current study, we find that protein kinase C is able to phosphorylate a key regulatory site in the B56delta subunit leading to activation of PP2A. In turn, activation of the B56delta-containing heterotrimeric form of PP2A is responsible for enhanced dephosphorylation of Ser40 of tyrosine hydroylase in response to stimulation of PKC. In support of this mechanism, down regulation of B56delta expression in N27 cells using RNAi was found to increase dopamine synthesis. Together these studies reveal molecular details of how protein kinase C is linked to reduced tyrosine hydroxylase activity via control of PP2A, and also add to the complexity of protein kinase/protein phosphatase interactions. PMID- 22046271 TI - Lung function is associated with arterial stiffness in children. AB - BACKGROUND: In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life. OBJECTIVE: To determine the relationship between lung function and carotid augmentation index (AIx), a measure of vascular stiffness, in 8-year old children. METHODS: Data on brachial blood pressure, lung function (FEV(1), FVC, FEV(1)/FVC, obtained by spirometry) and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry) was available in 249 community-based 8 year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance) to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS) exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention) as covariates. RESULTS: In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised beta = -0.17,b = -6.72, partial R(2) = .02, p = 0.03), FVC (standardised beta = -0.29, b = 9.31, partial R(2) = 0.04, p<0.001) and FEV1/FVC (standardised beta = .13, b = 18.4, partial R(2) = 0.02, p = 0.04). CONCLUSION: Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems. PMID- 22046272 TI - Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells. AB - Plasmacytoid dendritic cells (pDCs) play a key role in detecting pathogens by producing large amounts of type I interferon (IFN) by sensing the presence of viral infections through the Toll-Like Receptor (TLR) pathway. TLR9 is a sensor of viral and bacterial DNA motifs and activates the IRF7 transcription factor which leads to type I IFN secretion by pDCs. However, during chronic hepatitis B virus (HBV) infection, pDCs display an impaired ability to secrete IFN-alpha following ex vivo stimulation with TLR9 ligands. Here we highlight several strategies used by HBV to block IFN-alpha production through a specific impairment of the TLR9 signaling. Our results show that HBV particle internalisation could inhibit TLR9- but not TLR7-mediated secretion of IFN-alpha by pDCs. We observed that HBV down-regulated TLR9 transcriptional activity in pDCs and B cells in which TLR9 mRNA and protein levels were reduced. HBV can interfere with TLR9 activity by blocking the MyD88-IRAK4 axis and Sendai virus targeting IRF7 to block IFN-alpha production. Neutralising CpG motif sequences were identified within HBV DNA genome of genotypes A to H which displayed a suppressive effect on TLR9-immune activation. Moreover, TLR9 mRNA and protein were downregulated in PBMCs from patients with HBV-associated chronic hepatitis and hepatocellular carcinoma. Thus HBV has developed several escape mechanisms to avoid TLR9 activation in both pDCs and B lymphocytes, which may in turn contribute to the establishment and/or persistence of chronic infection. PMID- 22046274 TI - Continuous three-dimensional control of a virtual helicopter using a motor imagery based brain-computer interface. AB - Brain-computer interfaces (BCIs) allow a user to interact with a computer system using thought. However, only recently have devices capable of providing sophisticated multi-dimensional control been achieved non-invasively. A major goal for non-invasive BCI systems has been to provide continuous, intuitive, and accurate control, while retaining a high level of user autonomy. By employing electroencephalography (EEG) to record and decode sensorimotor rhythms (SMRs) induced from motor imaginations, a consistent, user-specific control signal may be characterized. Utilizing a novel method of interactive and continuous control, we trained three normal subjects to modulate their SMRs to achieve three dimensional movement of a virtual helicopter that is fast, accurate, and continuous. In this system, the virtual helicopter's forward-backward translation and elevation controls were actuated through the modulation of sensorimotor rhythms that were converted to forces applied to the virtual helicopter at every simulation time step, and the helicopter's angle of left or right rotation was linearly mapped, with higher resolution, from sensorimotor rhythms associated with other motor imaginations. These different resolutions of control allow for interplay between general intent actuation and fine control as is seen in the gross and fine movements of the arm and hand. Subjects controlled the helicopter with the goal of flying through rings (targets) randomly positioned and oriented in a three-dimensional space. The subjects flew through rings continuously, acquiring as many as 11 consecutive rings within a five-minute period. In total, the study group successfully acquired over 85% of presented targets. These results affirm the effective, three-dimensional control of our motor imagery based BCI system, and suggest its potential applications in biological navigation, neuroprosthetics, and other applications. PMID- 22046273 TI - Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. AB - The brain contains numerous mononuclear phagocytes called microglia. These cells express the transmembrane tyrosine kinase receptor for the macrophage growth factor colony stimulating factor-1 (CSF-1R). Using a CSF-1R-GFP reporter mouse strain combined with lineage defining antibody staining we show in the postnatal mouse brain that CSF-1R is expressed only in microglia and not neurons, astrocytes or glial cells. To study CSF-1R function we used mice homozygous for a null mutation in the Csflr gene. In these mice microglia are >99% depleted at embryonic day 16 and day 1 post-partum brain. At three weeks of age this microglial depletion continues in most regions of the brain although some contain clusters of rounded microglia. Despite the loss of microglia, embryonic brain development appears normal but during the post-natal period the brain architecture becomes perturbed with enlarged ventricles and regionally compressed parenchyma, phenotypes most prominent in the olfactory bulb and cortex. In the cortex there is increased neuronal density, elevated numbers of astrocytes but reduced numbers of oligodendrocytes. Csf1r nulls rarely survive to adulthood and therefore to study the role of CSF-1R in olfaction we used the viable null mutants in the Csf1 (Csf1(op)) gene that encodes one of the two known CSF-1R ligands. Food-finding experiments indicate that olfactory capacity is significantly impaired in the absence of CSF-1. CSF-1R is therefore required for the development of microglia, for a fully functional olfactory system and the maintenance of normal brain structure. PMID- 22046275 TI - Reduced distractibility in a remote culture. AB - BACKGROUND: In visual processing, there are marked cultural differences in the tendency to adopt either a global or local processing style. A remote culture (the Himba) has recently been reported to have a greater local bias in visual processing than Westerners. Here we give the first evidence that a greater, and remarkable, attentional selectivity provides the basis for this local bias. METHODOLOGY/PRINCIPAL FINDINGS: In Experiment 1, Eriksen-type flanker interference was measured in the Himba and in Western controls. In both groups, responses to the direction of a task-relevant target arrow were affected by the compatibility of task-irrelevant distractor arrows. However, the Himba showed a marked reduction in overall flanker interference compared to Westerners. The smaller interference effect in the Himba occurred despite their overall slower performance than Westerners, and was evident even at a low level of perceptual load of the displays. In Experiment 2, the attentional selectivity of the Himba was further demonstrated by showing that their attention was not even captured by a moving singleton distractor. CONCLUSIONS/SIGNIFICANCE: We argue that the reduced distractibility in the Himba is clearly consistent with their tendency to prioritize the analysis of local details in visual processing. PMID- 22046276 TI - myKaryoView: a light-weight client for visualization of genomic data. AB - The Distributed Annotation System (DAS) is a protocol for easy sharing and integration of biological annotations. In order to visualize feature annotations in a genomic context a client is required. Here we present myKaryoView, a simple light-weight DAS tool for visualization of genomic annotation. myKaryoView has been specifically configured to help analyse data derived from personal genomics, although it can also be used as a generic genome browser visualization. Several well-known data sources are provided to facilitate comparison of known genes and normal variation regions. The navigation experience is enhanced by simultaneous rendering of different levels of detail across chromosomes. A simple interface is provided to allow searches for any SNP, gene or chromosomal region. User-defined DAS data sources may also be added when querying the system. We demonstrate myKaryoView capabilities for adding user-defined sources with a set of genetic profiles of family-related individuals downloaded directly from 23andMe. myKaryoView is a web tool for visualization of genomic data specifically designed for direct-to-consumer genomic data that uses publicly available data distributed throughout the Internet. It does not require data to be held locally and it is capable of rendering any feature as long as it conforms to DAS specifications. Configuration and addition of sources to myKaryoView can be done through the interface. Here we show a proof of principle of myKaryoView's ability to display personal genomics data with 23andMe genome data sources. The tool is available at: http://mykaryoview.com. PMID- 22046277 TI - Effects of short-term continuous subcutaneous insulin infusion on fasting plasma fibroblast growth factor-21 levels in patients with newly diagnosed type 2 diabetes mellitus. AB - BACKGROUND: To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) on plasma fibroblast growth factor-21 (FGF-21) levels in patients with newly diagnosed type 2 diabetes mellitus (nT2DM). METHOD: Sixty eight patients with nT2DM (nT2DM group), and 52 gender-, age- and body mass index (BMI) -matched normal glucose tolerance (NGT group) controls participated in the study. 30 nT2DM patients with FBG >= 14.0 mmol/L were treated with CSII for 2 weeks, and were underwent a euglycemic-hyperinsulinemic clamp pre- and post treatment. Plasma FGF-21 concentrations were measured with a commercial ELISA kit. The relationship between plasma FGF-21 levels and metabolic parameters was also analyzed. RESULTS: Fasting plasma FGF-21 levels were higher in the nT2DM group than in NGT groups (1.60 +/- 0.08 vs. 1.13 +/- 0.26 ug/L, P<0.01). In nT2DM patients, fasting plasma FGF-21 concentrations were significantly decreased after CSII treatment for 2 weeks (1.60 +/- 0.08 vs.1.30 +/- 0.05 ug/L, P<0.05), accompanied by a significant increase in the whole body glucose uptake (M value) and blood glucose control. The changes in plasma FGF-21 levels (DeltaFGF-21) were positively associated with the amelioration of insulin resistance shown by the changes in M value. CONCLUSION: Plasma FGF-21 level is associated with whole body insulin sensitivity and significantly reduced following short-term CSII treatment. PMID- 22046278 TI - Loss-of-function of Constitutive Expresser of Pathogenesis Related Genes5 affects potassium homeostasis in Arabidopsis thaliana. AB - Here, we demonstrate that the reduction in leaf K(+) observed in a mutant previously identified in an ionomic screen of fast neutron mutagenized Arabidopsis thaliana is caused by a loss-of-function allele of CPR5, which we name cpr5-3. This observation establishes low leaf K(+) as a new phenotype for loss-of-function alleles of CPR5. We investigate the factors affecting this low leaf K(+) in cpr5 using double mutants defective in salicylic acid (SA) and jasmonic acid (JA) signalling, and by gene expression analysis of various channels and transporters. Reciprocal grafting between cpr5 and Col-0 was used to determine the relative importance of the shoot and root in causing the low leaf K(+) phenotype of cpr5. Our data show that loss-of-function of CPR5 in shoots primarily determines the low leaf K(+) phenotype of cpr5, though the roots also contribute to a lesser degree. The low leaf K(+) phenotype of cpr5 is independent of the elevated SA and JA known to occur in cpr5. In cpr5 expression of genes encoding various Cyclic Nucleotide Gated Channels (CNGCs) are uniquely elevated in leaves. Further, expression of HAK5, encoding the high affinity K(+) uptake transporter, is reduced in roots of cpr5 grown with high or low K(+) supply. We suggest a model in which low leaf K(+) in cpr5 is driven primarily by enhanced shoot-to-root K(+) export caused by a constitutive activation of the expression of various CNGCs. This activation may enhance K(+) efflux, either indirectly via enhanced cytosolic Ca(2+) and/or directly by increased K(+) transport activity. Enhanced shoot-to-root K(+) export may also cause the reduced expression of HAK5 observed in roots of cpr5, leading to a reduction in uptake of K(+). All ionomic data presented is publically available at www.ionomicshub.org. PMID- 22046279 TI - Carbon monoxide induced PPARgamma SUMOylation and UCP2 block inflammatory gene expression in macrophages. AB - Carbon monoxide (CO) dampens pro-inflammatory responses in a peroxisome proliferator-activated receptor-gamma (PPARgamma) and p38 mitogen-activated protein kinase (MAPK) dependent manner. Previously, we demonstrated that CO inhibits lipopolysaccharide (LPS)-induced expression of the proinflammatory early growth response-1 (Egr-1) transcription factor in macrophages via activation of PPARgamma. Here, we further characterize the molecular mechanisms by which CO modulates the activity of PPARgamma and Egr-1 repression. We demonstrate that CO enhances SUMOylation of PPARgamma which we find was attributed to mitochondrial ROS generation. Ectopic expression of a SUMOylation-defective PPARgamma-K365R mutant partially abolished CO-mediated suppression of LPS-induced Egr-1 promoter activity. Expression of a PPARgamma-K77R mutant did not impair the effect of CO. In addition to PPARgamma SUMOylation, CO-activated p38 MAPK was responsible for Egr-1 repression. Blocking both CO-induced PPARgamma SUMOylation and p38 activation, completely reversed the effects of CO on inflammatory gene expression. In primary macrophages isolated form C57/BL6 male mice, we identify mitochondrial ROS formation by CO as the upstream trigger for the observed effects on Egr-1 in part through uncoupling protein 2 (UCP2). Macrophages derived from bone marrow isolated from Ucp2 gene Knock-Out C57/BL6 mice (Ucp2(-/-)), produced significantly less ROS with CO exposure versus wild-type macrophages. Moreover, absence of UCP2 resulted in a complete loss of CO mediated Egr-1 repression. Collectively, these results indentify p38 activation, PPARgamma SUMOylation and ROS formation via UCP2 as a cooperative system by which CO impacts the inflammatory response. PMID- 22046280 TI - Non-invasive cytology brush PCR diagnostic testing in mucosal leishmaniasis: superior performance to conventional biopsy with histopathology. AB - BACKGROUND: Traditional methods of diagnosing mucosal leishmaniasis (ML), such as biopsy with histopathology, are insensitive and require collection of an invasive diagnostic specimen. METHODS: We compared standard invasive procedures including biopsy histopathology, biopsy PCR, and leishmanin skin test (LST) to a novel, non invasive, cytology-brush based PCR for the diagnosis of ML in Lima, Peru. Consensus reference standard was 2/4 tests positive, and outcome measures were sensitivity and specificity. Leishmania species identification was performed by PCR-based assays of positive specimens. RESULTS: Twenty-eight patients were enrolled, 23 of whom fulfilled criteria for a diagnosis of ML. Sensitivity and specificity of biopsy with histopathology were 21.7% [95% CI 4.9-38.5%] and 100%; 69.6% [95% CI 50.8-88.4%] and 100% for LST; 95.7% [95% CI 87.4-100%] and 100% for biopsy PCR; and 95.7% [95% CI 87.4-100%] and 90% [95% CI 71.4-100%] for cytology brush PCR using both Cervisoft(r) and Histobrush(r) cervical cytology brushes. Represented species identified by PCR-RFLP included: L. (V). braziliensis (n = 4), and L. (V). peruviana (n = 3). CONCLUSIONS: Use of commercial grade cytology brush PCR for diagnosis of ML is sensitive, rapid, well tolerated, and carries none of the risks of invasive diagnostic procedures such as biopsy. Further optimization is required for adequate species identification. Further evaluation of this method in field and other settings is warranted. PMID- 22046281 TI - Increased feeding and food hoarding following food deprivation are associated with activation of dopamine and orexin neurons in male Brandt's voles. AB - Small mammals usually face energetic challenges, such as food shortage, in the field. They have thus evolved species-specific adaptive strategies for survival and reproductive success. In the present study, we examined male Brandt's voles (Lasiopodomys brandtii) for their physiological, behavioral, and neuronal responses to food deprivation (FD) and subsequent re-feeding. Although 48 hr FD induced a decrease in body weight and the resting metabolic rate (RMR), such decreases did not reach statistical significance when compared to the control males that did not experience FD. During the first 2 hr of re-feeding following 48 hr FD, voles showed higher levels of feeding than controls. However, when permitted to hoard food, FD voles showed an increase in food hoarding, rather than feeding, compared to the controls. Further, both feeding and food hoarding induced an increase in neuronal activation, measured by Fos-ir, in a large number of brain areas examined. Interestingly, feeding and food hoarding also induced an increase in the percentage of tyrosine hydroxylase immunoreactive (TH-ir) cells that co-expressed Fos-ir in the ventral tegmental area (VTA), whereas both FD and feeding induced an increase in the percentage of orexin-ir cells that co expressed Fos-ir in the lateral hypothalamus (LH). Food hoarding also increased orexin-ir/Fos-ir labeling in the LH. Together, our data indicate that food deprived male Brandt's voles display enhanced feeding or food hoarding dependent upon an environmental setting. In addition, changes in central dopamine and orexin activities in selected brain areas are associated with feeding and hoarding behaviors following FD and subsequent re-feeding. PMID- 22046282 TI - Silencing GADD153/CHOP gene expression protects against Alzheimer's disease-like pathology induced by 27-hydroxycholesterol in rabbit hippocampus. AB - Endoplasmic reticulum (ER) stress is suggested to play a key role in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). Sustained ER stress leads to activation of the growth arrest and leucine zipper transcription factor, DNA damage inducible gene 153 (gadd153; also called CHOP). Activated gadd153 can generate oxidative damage and reactive oxygen species (ROS), increase beta-amyloid (Abeta) levels, disturb iron homeostasis and induce inflammation as well as cell death, which are all pathological hallmarks of AD. Epidemiological and laboratory studies suggest that cholesterol dyshomeostasis contributes to the pathogenesis of AD. We have previously shown that the cholesterol oxidized metabolite 27-hydroxycholesterol (27-OHC) triggers AD-like pathology in organotypic slices. However, the extent to which gadd153 mediates 27 OHC effects has not been determined. We silenced gadd153 gene with siRNA and determined the effects of 27-OHC on AD hallmarks in organotypic slices from adult rabbit hippocampus. siRNA to gadd153 reduced 27-OHC-induced Abeta production by mechanisms involving reduction in levels of beta-amyloid precursor protein (APP) and beta-secretase (BACE1), the enzyme that initiates cleavage of APP to yield Abeta peptides. Additionally, 27-OHC-induced tau phosphorylation, ROS generation, TNF-alpha activation, and iron and apoptosis-regulatory protein levels alteration were also markedly reduced by siRNA to gadd153. These data suggest that ER stress mediated gadd153 activation plays a central role in the triggering of AD pathological hallmarks that result from incubation of hippocampal slices with 27 OHC. Our results add important insights into cellular mechanisms that underlie the potential contribution of cholesterol metabolism in AD pathology, and suggest that preventing gadd153 activation protects against AD related to cholesterol oxidized products. PMID- 22046283 TI - Assessing the cost of helping: the roles of body condition and oxidative balance in the Seychelles warbler (Acrocephalus sechellensis). AB - In cooperatively breeding species, helping close relatives may provide important fitness benefits. However, helping can be energetically expensive and may result in increased generation of reactive oxygen species. Consequently, an oxidant/antioxidant imbalance can lead to higher oxidative stress susceptibility. Given the potential costs of helping, it may be that only individuals with a sufficiently good body condition and/or stable oxidative balance can afford to help. Knowledge about relationships between social status and oxidative balance in cooperatively breeding systems is still limited. Studying these relationships is important for understanding the costs of helping and physiological pressures of reproduction. Here we evaluate the relationship between helping behaviour, body condition and oxidative balance in a wild population of the cooperatively breeding Seychelles warbler (Acrocephalus sechellensis). In this species, some subordinate individuals help dominant birds with the rearing of young, while others refrain from any assistance. We assessed body condition and oxidative parameters of birds of different social status caught during different breeding stages. We found that, prior to breeding, female subordinates that did not subsequently help (non-helpers) had significantly lower body condition and higher ROMs (reactive oxygen metabolites) than helpers and dominants. During the later stages of breeding, body condition was low in dominants and helpers, but high in non-helpers. Differences in oxidative balance between individuals of different social status were found only during nest care: Dominant males occupied with guarding behaviours tended to have relatively high oxidative stress susceptibility. Furthermore, dominant and helper females showed elevated antioxidant capacity (measured as OXY) in the weeks just prior to egg-laying, possibly representing a change in their reproductive physiology. The results imply that an individuals' oxidative balance may be influenced by factors related to reproduction, which can differ with sex and--within cooperative breeding systems--social status. PMID- 22046284 TI - Scatter-hoarding rodents prefer slightly astringent food. AB - The mutualistic interaction between scatter-hoarding rodents and their seed plants is highly complex yet poorly understood. Plants may benefit from the seed dispersal behavior of rodents, as long as seed consumption is minimized. In parallel, rodents may maximize foraging efficiency and cache high-quality resources for future consumption. Defensive compounds, such as tannins, are thought to be a major mechanism for plant control over rodent behavior. However, previous studies, using naturally occurring seeds, have not provided conclusive evidence supporting this hypothesis. Here, we test the importance of tannin concentrations on the scatter-hoarding behavior of rodents by using an artificial seed system. We combined feeding trials and field observations to examine the overall impact of seed tannin concentrations on rodent behavior and health. We found that rodents favored seeds with an intermediate amount of tannin (~5%) in the field. Meanwhile, in rodents that were fed a diet with different tannin content, only diets with high tannin content (25%, 15%, and 10%) caused a significant negative influence on rodent survival and health. Significant differences were not found among treatments with tannin levels of 0-5%. In contrast to many existing studies, our results clearly demonstrate that scatter hoarding rodents prefer slightly 'astringent' food. In the co-evolutionary arms race between plants and animals, our results suggest that while tannins may play a significant role in reducing general predation levels by the faunal community, they have no precise control over the behavior of their mutualistic partner. Instead, the two partners appear to have reached an evolutionary point where both parties receive adequate benefits, with the year-to-year outcome being dependent on a wide range of factors beyond the control of either partner. PMID- 22046285 TI - Identification of antigens specific to non-tuberculous mycobacteria: the Mce family of proteins as a target of T cell immune responses. AB - The lack of an effective TB vaccine hinders current efforts in combating the TB pandemic. One theory as to why BCG is less protective in tropical countries is that exposure to non-tuberculous mycobacteria (NTM) reduces BCG efficacy. There are currently several new TB vaccines in clinical trials, and NTM exposure may also be relevant in this context. NTM exposure cannot be accurately evaluated in the absence of specific antigens; those which are known to be present in NTM and absent from M. tuberculosis and BCG. We therefore used a bioinformatic pipeline to define proteins which are present in common NTM and absent from the M. tuberculosis complex, using protein BLAST, TBLASTN and a short sequence protein BLAST to ensure the specificity of this process. We then assessed immune responses to these proteins, in healthy South Africans and in patients from the United Kingdom and United States with documented exposure to NTM. Low level responses were detected to a cluster of proteins from the mammalian cell entry family, and to a cluster of hypothetical proteins, using ex vivo ELISpot and a 6 day proliferation assay. These early findings may provide a basis for characterising exposure to NTM at a population level, which has applications in the field of TB vaccine design as well as in the development of diagnostic tests. PMID- 22046286 TI - A novel evolution-based method for detecting gene-gene interactions. AB - BACKGROUND: The rapid advance in large-scale SNP-chip technologies offers us great opportunities in elucidating the genetic basis of complex diseases. Methods for large-scale interactions analysis have been under development from several sources. Due to several difficult issues (e.g., sparseness of data in high dimensions and low replication or validation rate), development of fast, powerful and robust methods for detecting various forms of gene-gene interactions continues to be a challenging task. METHODOLOGY/PRINCIPAL FINDINGS: In this article, we have developed an evolution-based method to search for genome-wide epistasis in a case-control design. From an evolutionary perspective, we view that human diseases originate from ancient mutations and consider that the underlying genetic variants play a role in differentiating human population into the healthy and the diseased. Based on this concept, traditional evolutionary measure, fixation index (Fst) for two unlinked loci, which measures the genetic distance between populations, should be able to reveal the responsible genetic interplays for disease traits. To validate our proposal, we first investigated the theoretical distribution of Fst by using extensive simulations. Then, we explored its power for detecting gene-gene interactions via SNP markers, and compared it with the conventional Pearson Chi-square test, mutual information based test and linkage disequilibrium based test under several disease models. The proposed evolution-based method outperformed these compared methods in dominant and additive models, no matter what the disease allele frequencies were. However, its performance was relatively poor in a recessive model. Finally, we applied the proposed evolution-based method to analysis of a published dataset. Our results showed that the P value of the Fst -based statistic is smaller than those obtained by the LD-based statistic or Poisson regression models. CONCLUSIONS/SIGNIFICANCE: With rapidly growing large-scale genetic association studies, the proposed evolution-based method can be a promising tool in the identification of epistatic effects. PMID- 22046287 TI - Molecular diversity of fungal phylotypes co-amplified alongside nematodes from coastal and deep-sea marine environments. AB - Nematodes and fungi are both ubiquitous in marine environments, yet few studies have investigated relationships between these two groups. Microbial species share many well-documented interactions with both free-living and parasitic nematode species, and limited data from previous studies have suggested ecological associations between fungi and nematodes in benthic marine habitats. This study aimed to further document the taxonomy and distribution of fungal taxa often co amplified from nematode specimens. A total of 15 fungal 18S rRNA phylotypes were isolated from nematode specimens representing both deep-sea and shallow water habitats; all fungal isolates displayed high pairwise sequence identities with published data in Genbank (99-100%) and unpublished high-throughput 454 environmental datasets (>95%). BLAST matches indicate marine fungal sequences amplified in this study broadly represent taxa within the phyla Ascomycota and Basidiomycota, and several phylotypes showed robust groupings with known taxa in phylogenetic topologies. In addition, some fungal phylotypes appeared to be present in disparate geographic habitats, suggesting cosmopolitan distributions or closely related species complexes in at least some marine fungi. The present study was only able to isolate fungal DNA from a restricted set of nematode taxa; further work is needed to fully investigate the taxonomic scope and function of nematode-fungal interactions. PMID- 22046288 TI - Multichannel detrended fluctuation analysis reveals synchronized patterns of spontaneous spinal activity in anesthetized cats. AB - The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA-alpha mean = 1.04[Formula: see text]0.09) or simultaneously from several lumbar segments (mDFA-alpha mean = 1.01[Formula: see text]0.06), where alpha = 0.5 indicates randomness while alpha = 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA [Formula: see text] = 0.992 as compared to initial conditions mDFA-alpha = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA-alpha = 0.924). In contrast to the classical methods, such as correlation and coherence quantification that define a relation between two sets of data, the mDFA method properly reveals the synchronization of multiple groups of neurons in several segments of the spinal cord. This method is envisaged as a useful tool to characterize the structure of higher order ensembles of cord dorsum spontaneous potentials after spinal cord or peripheral nerve lesions. PMID- 22046289 TI - The nature and perception of fluctuations in human musical rhythms. AB - Although human musical performances represent one of the most valuable achievements of mankind, the best musicians perform imperfectly. Musical rhythms are not entirely accurate and thus inevitably deviate from the ideal beat pattern. Nevertheless, computer generated perfect beat patterns are frequently devalued by listeners due to a perceived lack of human touch. Professional audio editing software therefore offers a humanizing feature which artificially generates rhythmic fluctuations. However, the built-in humanizing units are essentially random number generators producing only simple uncorrelated fluctuations. Here, for the first time, we establish long-range fluctuations as an inevitable natural companion of both simple and complex human rhythmic performances. Moreover, we demonstrate that listeners strongly prefer long-range correlated fluctuations in musical rhythms. Thus, the favorable fluctuation type for humanizing interbeat intervals coincides with the one generically inherent in human musical performances. PMID- 22046290 TI - Impact of definitive therapy with beta-lactam monotherapy or combination with an aminoglycoside or a quinolone for Pseudomonas aeruginosa bacteremia. AB - BACKGROUND: Bacteremia by Pseudomonas aeruginosa represents one severe infection. It is not clear whether beta-lactam monotherapy leads to similar rates of treatment success compared to combinations of beta-lactams with aminoglycosides or quinolones. METHODS: Retrospective cohort study from 3 tertiary hospitals (2 in Greece and 1 in Italy). Pseudomonas aeruginosa isolates were susceptible to a beta-lactam and an aminoglycoside or a quinolone. Patients received appropriate therapy for at least 48 hours. Primary outcome of interest was treatment success in patients with definitive beta-lactam combination therapy compared to monotherapy. Secondary outcomes were treatment success keeping the same empirical and definitive regimen, mortality, and toxicity. RESULTS: Out of 92 bacteremias there were 54 evaluable episodes for the primary outcome (20 received monotherapy). Treatment success was higher with combination therapy (85%) compared to beta-lactam monotherapy (65%), however not statistically significantly [Odds ratio (OR) 3.1; 95% Confidence Interval (CI) 0.69-14.7, p = 0.1]. Very long (>2 months) hospitalisation before bacteremia was the only factor independently associated with treatment success (OR 0.73; 95% CI 0.01-0.95, p = 0.046), however this result entailed few episodes. All-cause mortality did not differ significantly between combination therapy [6/31 (19%)] and monotherapy [8/19 (42%)], p = 0.11. Only Charlson comorbidity index was associated with excess mortality (p = 0.03). CONCLUSION: Our study, in accordance with previous ones, indicates that the choice between monotherapy and combination therapy may not affect treatment success significantly. However, our study does not have statistical power to identify small or moderate differences. A large randomized controlled trial evaluating this issue is justified. PMID- 22046291 TI - Effect of DNA groove binder distamycin A upon chromatin structure. AB - BACKGROUND: Distamycin A is a prototype minor groove binder, which binds to B form DNA, preferentially at A/T rich sites. Extensive work in the past few decades has characterized the binding at the level of double stranded DNA. However, effect of the same on physiological DNA, i.e. DNA complexed in chromatin, has not been well studied. Here we elucidate from a structural perspective, the interaction of distamycin with soluble chromatin, isolated from Sprague-Dawley rat. METHODOLOGY/PRINCIPAL FINDINGS: Chromatin is a hierarchical assemblage of DNA and protein. Therefore, in order to characterize the interaction of the same with distamycin, we have classified the system into various levels, according to the requirements of the method adopted, and the information to be obtained. Isothermal titration calorimetry has been employed to characterize the binding at the levels of chromatin, chromatosome and chromosomal DNA. Thermodynamic parameters obtained thereof, identify enthalpy as the driving force for the association, with comparable binding affinity and free energy for chromatin and chromosomal DNA. Reaction enthalpies at different temperatures were utilized to evaluate the change in specific heat capacity (DeltaCp), which, in turn, indicated a possible binding associated structural change. Ligand induced structural alterations have been monitored by two complementary methods--dynamic light scattering, and transmission electron microscopy. They indicate compaction of chromatin. Using transmission electron microscopy, we have visualized the effect of distamycin upon chromatin architecture at di- and trinucleosome levels. Our results elucidate the simultaneous involvement of linker bending and internucleosomal angle contraction in compaction process induced by distamycin. CONCLUSIONS/SIGNIFICANCE: We summarize here, for the first time, the thermodynamic parameters for the interaction of distamycin with soluble chromatin, and elucidate its effect on chromatin architecture. The study provides insight into a ligand induced compaction phenomenon, and suggests new mechanisms of chromatin architectural alteration. PMID- 22046292 TI - Physiological phenomenology of neurally-mediated syncope with management implications. AB - BACKGROUND: Due to lack of efficacy in recent trials, current guidelines for the treatment of neurally-mediated (vasovagal) syncope do not promote cardiac pacemaker implantation. However, the finding of asystole during head-up tilt induced (pre)syncope may lead to excessive cardioinhibitory syncope diagnosis and treatment with cardiac pacemakers as blood pressure is often discontinuously measured. Furthermore, physicians may be more inclined to implant cardiac pacemakers in older patients. We hypothesized that true cardioinhibitory syncope in which the decrease in heart rate precedes the fall in blood pressure is a very rare finding which might explain the lack of efficacy of pacemakers in neurally mediated syncope. METHODS: We studied 173 consecutive patients referred for unexplained syncope (114 women, 59 men, 42 +/- 1 years, 17 +/- 2 syncopal episodes). All had experienced (pre)syncope during head-up tilt testing followed by additional lower body negative suction. We classified hemodynamic responses according to the modified Vasovagal Syncope International Study (VASIS) classification as mixed response (VASIS I), cardioinhibitory without (VASIS IIa) or with asystole (VASIS IIb), and vasodepressor (VASIS III). Then, we defined the exact temporal relationship between hypotension and bradycardia to identify patients with true cardioinhibitory syncope. RESULTS: Of the (pre)syncopal events during tilt testing, 63% were classified as VASIS I, 6% as VASIS IIb, 2% as VASIS IIa, and 29% as VASIS III. Cardioinhibitory responses (VASIS class II) progressively decreased from the youngest to the oldest age quartile. With more detailed temporal analysis, blood pressure reduction preceded the heart-rate decrease in all but six individuals (97%) overall and in 10 out of 11 patients with asystole (VASIS IIb). CONCLUSIONS: Hypotension precedes bradycardia onset during head-up tilt-induced (pre)syncope in the vast majority of patients, even in those classified as cardioinhibitory syncope according to the modified VASIS classification. Furthermore, cardioinhibitory syncope becomes less frequent with increasing age. PMID- 22046293 TI - Why do woodpeckers resist head impact injury: a biomechanical investigation. AB - Head injury is a leading cause of morbidity and death in both industrialized and developing countries. It is estimated that brain injuries account for 15% of the burden of fatalities and disabilities, and represent the leading cause of death in young adults. Brain injury may be caused by an impact or a sudden change in the linear and/or angular velocity of the head. However, the woodpecker does not experience any head injury at the high speed of 6-7 m/s with a deceleration of 1000 g when it drums a tree trunk. It is still not known how woodpeckers protect their brain from impact injury. In order to investigate this, two synchronous high-speed video systems were used to observe the pecking process, and the force sensor was used to measure the peck force. The mechanical properties and macro/micro morphological structure in woodpecker's head were investigated using a mechanical testing system and micro-CT scanning. Finite element (FE) models of the woodpecker's head were established to study the dynamic intracranial responses. The result showed that macro/micro morphology of cranial bone and beak can be recognized as a major contributor to non-impact-injuries. This biomechanical analysis makes it possible to visualize events during woodpecker pecking and may inspire new approaches to prevention and treatment of human head injury. PMID- 22046294 TI - Protective CD8 memory T cell responses to mouse melanoma are generated in the absence of CD4 T cell help. AB - BACKGROUND: We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma, followed by surgical tumor excision, induces protective memory CD8 T cell responses to melanoma/melanocyte antigens. We also showed that persistence of these CD8 T cells is supported, in an antigen dependent fashion, by concurrent autoimmune melanocyte destruction. Herein we explore the requirement of CD4 T cell help in priming and maintaining this protective CD8 T cell response to melanoma. METHODOLOGY AND PRINCIPAL FINDINGS: To induce melanoma/melanocyte antigen-specific CD8 T cells, B16 tumor bearing mice were depleted of regulatory T cells (T(reg)) by either temporary, or long term continuous treatment with anti-CD4 (mAb clone GK1.5). Total depletion of CD4 T cells led to significant priming of IFN-gamma-producing CD8 T cell responses to TRP-2 and gp100. Surprisingly, treatment with anti-CD25 (mAb clone PC61), to specifically deplete T(reg) cells while leaving help intact, was ineffective at priming CD8 T cells. Thirty to sixty days after primary tumors were surgically excised, mice completely lacking CD4 T cell help developed autoimmune vitiligo, and maintained antigen-specific memory CD8 T cell responses that were highly effective at producing cytokines (IFN-gamma, TNF-alpha, and IL-2). Mice lacking total CD4 T cell help also mounted protection against re-challenge with B16 melanoma sixty days after primary tumor excision. CONCLUSIONS AND SIGNIFICANCE: This work establishes that CD4 T cell help is dispensable for the generation of protective memory T cell responses to melanoma. Our findings support further use of CD4 T cell depletion therapy for inducing long-lived immunity to cancer. PMID- 22046295 TI - Differential roles of hyperglycemia and hypoinsulinemia in diabetes induced retinal cell death: evidence for retinal insulin resistance. AB - Diabetes pathology derives from the combination of hyperglycemia and hypoinsulinemia or insulin resistance leading to diabetic complications including diabetic neuropathy, nephropathy and retinopathy. Diabetic retinopathy is characterized by numerous retinal defects affecting the vasculature and the neuro retina, but the relative contributions of the loss of retinal insulin signaling and hyperglycemia have never been directly compared. In this study we tested the hypothesis that increased retinal insulin signaling and glycemic normalization would exert differential effects on retinal cell survival and retinal physiology during diabetes. We have demonstrated in this study that both subconjunctival insulin administration and systemic glycemic reduction using the sodium-glucose linked transporter inhibitor phloridzin affected the regulation of retinal cell survival in diabetic rats. Both treatments partially restored the retinal insulin signaling without increasing plasma insulin levels. Retinal transcriptomic and histological analysis also clearly demonstrated that local administration of insulin and systemic glycemia normalization use different pathways to counteract the effects of diabetes on the retina. While local insulin primarily affected inflammation-associated pathways, systemic glycemic control affected pathways involved in the regulation of cell signaling and metabolism. These results suggest that hyperglycemia induces resistance to growth factor action in the retina and clearly demonstrate that both restoration of glycemic control and retinal insulin signaling can act through different pathways to both normalize diabetes-induced retinal abnormality and prevent vision loss. PMID- 22046296 TI - An integrated analysis of miRNA and mRNA expressions in non-small cell lung cancers. AB - Using DNA microarrays, we generated both mRNA and miRNA expression data from 6 non-small cell lung cancer (NSCLC) tissues and their matching normal control from adjacent tissues to identify potential miRNA markers for diagnostics. We demonstrated that hsa-miR-96 is significantly and consistently up-regulated in all 6 NSCLCs. We validated this result in an independent set of 35 paired tumors and their adjacent normal tissues, as well as their sera that are collected before surgical resection or chemotherapy, and the results suggested that hsa-miR 96 may play an important role in NSCLC development and has great potential to be used as a noninvasive marker for diagnosing NSCLC. We predicted potential miRNA target mRNAs based on different methods (TargetScan and miRanda). Further classification of miRNA regulated genes based on their relationship with miRNAs revealed that hsa-miR-96 and certain other miRNAs tend to down-regulate their target mRNAs in NSCLC development, which have expression levels permissive to direct interaction between miRNAs and their target mRNAs. In addition, we identified a significant correlation of miRNA regulation with genes coincide with high density of CpG islands, which suggests that miRNA may represent a primary regulatory mechanism governing basic cellular functions and cell differentiations, and such mechanism may be complementary to DNA methylation in repressing or activating gene expression. PMID- 22046297 TI - Sensory coding by cerebellar mossy fibres through inhibition-driven phase resetting and synchronisation. AB - Temporal coding of spike-times using oscillatory mechanisms allied to spike-time dependent plasticity could represent a powerful mechanism for neuronal communication. However, it is unclear how temporal coding is constructed at the single neuronal level. Here we investigate a novel class of highly regular, metronome-like neurones in the rat brainstem which form a major source of cerebellar afferents. Stimulation of sensory inputs evoked brief periods of inhibition that interrupted the regular firing of these cells leading to phase shifted spike-time advancements and delays. Alongside phase-shifting, metronome cells also behaved as band-pass filters during rhythmic sensory stimulation, with maximal spike-stimulus synchronisation at frequencies close to the idiosyncratic firing frequency of each neurone. Phase-shifting and band-pass filtering serve to temporally align ensembles of metronome cells, leading to sustained volleys of near-coincident spike-times, thereby transmitting synchronised sensory information to downstream targets in the cerebellar cortex. PMID- 22046298 TI - Overexpression of active Aurora-C kinase results in cell transformation and tumour formation. AB - Aurora kinases belong to a conserved family of serine/threonine kinases key regulators of cell cycle progression. Aurora-A and Aurora-B are expressed in somatic cells and involved mainly in mitosis while Aurora-C is expressed during spermatogenesis and oogenesis and is involved in meiosis. Aurora-C is hardly detectable in normal somatic cells. However all three kinases are overexpressed in many cancer lines. Aurora-A possesses an oncogenic activity while Aurora-B does not. Here we investigated whether Aurora-C possesses such an oncogenic activity. We report that overexpression of Aurora-C induces abnormal cell division resulting in centrosome amplification and multinucleation in both transiently transfected cells and in stable cell lines. Only stable NIH3T3 cell clones overexpressing active Aurora-C formed foci of colonies when grown on soft agar, indicating that a gain of Aurora-C activity is sufficient to transform cells. Furthermore, we reported that NIH-3T3 stable cell lines overexpressing Aurora-C induced tumour formation when injected into nude mice, demonstrating the oncogenic activity of enzymatically active Aurora kinase C. Interestingly enough tumor aggressiveness was positively correlated with the quantity of active kinase, making Aurora-C a potential anti-cancer therapeutic target. PMID- 22046299 TI - Profiling of Burkholderia cepacia secretome at mid-logarithmic and early stationary phases of growth. AB - BACKGROUND: Burkholderia cepacia is a Gram-negative pathogen that causes serious respiratory infections in immunocompromised patients and individuals with cystic fibrosis. This bacterium is known to release extracellular proteins that may be involved in virulence. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, B. cepacia grown to mid-logarithmic and early-stationary phases were investigated on their ability to invade and survive intracellularly in A549 lung epithelial cells in order to discern the fate of these bacteria in the pathogenesis of B. cepacia lung infections in in vitro condition. The early-stationary phase B. cepacia was demonstrated to be more invasive than mid-logarithmic phase. In addition, culture supernatants of B. cepacia obtained from these phases of growth were also demonstrated to cause different cytotoxic potency on the A549 human lung epithelial cells. Profiling of the supernatants using the gel-based proteomics approach identified 43 proteins that were commonly released in both the growth phases and 40 proteins newly-released at the early-stationary phase. The latter proteins may account for the higher cytotoxic activity of the early-stationary culture supernatant compared to that obtained at the mid-logarithmic phase. Among the newly-released proteins in the early-stationary phase supernatant were flagellar hook-associated domain protein (FliD), flagellar hook-associated protein (FlgK), TonB-dependent siderophore (Fiu), Elongation factor G (FusA), phosphoglycerate kinase (Pgk) and sulfatase (AslA) which are known for their virulence. CONCLUSION/SIGNIFICANCE: Differences in the ability of B. cepacia to invade and survive intracellularly inside the epithelial cells at different phases of growth may improve our understanding of the varied disease progressions associated with B. cepacia infections. In addition, the identified culture supernatant proteins may be used as targets for the development of new strategies to control B. cepacia infection using agents that can block their release. PMID- 22046300 TI - miRConnect: identifying effector genes of miRNAs and miRNA families in cancer cells. AB - micro(mi)RNAs are small non-coding RNAs that negatively regulate expression of most mRNAs. They are powerful regulators of various differentiation stages, and the expression of genes that either negatively or positively correlate with expressed miRNAs is expected to hold information on the biological state of the cell and, hence, of the function of the expressed miRNAs. We have compared the large amount of available gene array data on the steady state system of the NCI60 cell lines to two different data sets containing information on the expression of 583 individual miRNAs. In addition, we have generated custom data sets containing expression information of 54 miRNA families sharing the same seed match. We have developed a novel strategy for correlating miRNAs with individual genes based on a summed Pearson Correlation Coefficient (sPCC) that mimics an in silico titration experiment. By focusing on the genes that correlate with the expression of miRNAs without necessarily being direct targets of miRNAs, we have clustered miRNAs into different functional groups. This has resulted in the identification of three novel miRNAs that are linked to the epithelial-to-mesenchymal transition (EMT) in addition to the known EMT regulators of the miR-200 miRNA family. In addition, an analysis of gene signatures associated with EMT, c-MYC activity, and ribosomal protein gene expression allowed us to assign different activities to each of the functional clusters of miRNAs. All correlation data are available via a web interface that allows investigators to identify genes whose expression correlates with the expression of single miRNAs or entire miRNA families. miRConnect.org will aid in identifying pathways regulated by miRNAs without requiring specific knowledge of miRNA targets. PMID- 22046301 TI - Effect of rickettsial toxin VapC on its eukaryotic host. AB - Rickettsia are intracellular bacteria typically associated with arthropods that can be transmitted to humans by infected vectors. Rickettsia spp. can cause mild to severe human disease with a possible protection effect of corticosteroids when antibiotic treatments are initiated. We identified laterally transferred toxin antitoxin (TA) genetic elements, including vapB/C, in several Rickettsia genomes and showed that they are functional in bacteria and eukaryotic cells. We also generated a plaque assay to monitor the formation of lytic plaques over time and demonstrated that chloramphenicol accelerates host cell lysis of vapB/C containing Rickettsia. Whole-genome expression, TUNEL and FISH assays on the infected cells following exposure to the antibiotic revealed early apoptosis of host cells, which was linked to over-transcription of bacterial vapB/C operons and subsequent cytoplasmic VapC toxin release. VapC that is expressed in Escherichia coli and Saccharomyces cerevisiae or microinjected into mammalian cells is toxic through RNase activity and is prevented by dexamethasone. This study provides the first biological evidence that toxin-antitoxin elements act as pathogenic factors in bacterial host cells, confirming comparative genomic evidence of their role in bacterial pathogenicity. Our results suggest that early mortality following antibiotic treatment of some bacterial infections can be prevented by administration of dexamethasone. PMID- 22046302 TI - Assessing the impacts of experimentally elevated temperature on the biological composition and molecular chaperone gene expression of a reef coral. AB - Due to the potential for increasing ocean temperatures to detrimentally impact reef-building corals, there is an urgent need to better understand not only the coral thermal stress response, but also natural variation in their sub-cellular composition. To address this issue, while simultaneously developing a molecular platform for studying one of the most common Taiwanese reef corals, Seriatopora hystrix, 1,092 cDNA clones were sequenced and characterized. Subsequently, RNA, DNA and protein were extracted sequentially from colonies exposed to elevated (30 degrees C) temperature for 48 hours. From the RNA phase, a heat shock protein-70 (hsp70)-like gene, deemed hsp/c, was identified in the coral host, and expression of this gene was measured with real-time quantitative PCR (qPCR) in both the host anthozoan and endosymbiotic dinoflagellates (genus Symbiodinium). While mRNA levels were not affected by temperature in either member, hsp/c expression was temporally variable in both and co-varied within biopsies. From the DNA phase, host and Symbiodinium hsp/c genome copy proportions (GCPs) were calculated to track changes in the biological composition of the holobiont during the experiment. While there was no temperature effect on either host or Symbiodinium GCP, both demonstrated significant temporal variation. Finally, total soluble protein was responsive to neither temperature nor exposure time, though the protein/DNA ratio varied significantly over time. Collectively, it appears that time, and not temperature, is a more important driver of the variation in these parameters, highlighting the need to consider natural variation in both gene expression and the molecular make-up of coral holobionts when conducting manipulative studies. This represents the first study to survey multiple macromolecules from both compartments of an endosymbiotic organism with methodologies that reflect their dual-compartmental nature, ideally generating a framework for assessing molecular-level changes within corals and other endosymbioses exposed to changes in their environment. PMID- 22046303 TI - Cloned, CD117 selected human amniotic fluid stem cells are capable of modulating the immune response. AB - Amniotic fluid stem (AFS) cells are broadly multipotent, can be expanded extensively in culture, are not tumorigenic and can be readily cryopreserved for cell banking. Mesenchymal stem cells (MSC) show immunomodulatory activity and secrete a wide spectrum of cytokines and chemokines that suppress inflammatory responses, block mixed lymphocyte reactions (MLR) and other immune reactions, and have proven therapeutic against conditions such as graft-versus-host disease. AFS cells resemble MSCs in many respects including surface marker expression and differentiation potential. We therefore hypothesized that AFS cells may exhibit similar immunomodulatory capabilities. We present data to demonstrate that direct contact with AFS cells inhibits lymphocyte activation. In addition, we show that cell-free supernatants derived from AFS cells primed with total blood monocytes or IL-1beta, a cytokine released by monocytes and essential in mediation of the inflammatory response, also inhibited lymphocyte activation. Further investigation of AFS cell-free supernatants by protein array revealed secretion of multiple factors in common with MSCs that are known to be involved in immune regulation including growth related oncogene (GRO) and monocyte chemotactic protein (MCP) family members as well as interleukin-6 (IL-6). AFS cells activated by PBMCs released several additional cytokines as compared to BM-MSCs, including macrophage inflammatory protein-3alpha (MIP-3alpha), MIP-1alpha and Activin. AFS cells also released higher levels of MCP-1 and lower levels of MCP-2 compared to BM-MSCs in response to IL-1beta activation. This suggests that there may be some AFS-specific mechanisms of inhibition of lymphocyte activation. Our results indicate that AFS cells are able to suppress inflammatory responses in vitro and that soluble factors are an essential component in the communication between lymphocytes and AFS cells. Their extensive self-renewal capacity, possibility for banking and absence of tumorigenicity may make AFS cells a superior source of stable, well characterized "off the shelf" immunomodulatory cells for a variety of immunotherapies. PMID- 22046304 TI - Homeostatic regulation of marginal zone B cells by invariant natural killer T cells. AB - Marginal zone B cells (MZB) mount a rapid antibody response, potently activate naive T cells, and are enriched in autoreactive B cells. MZBs express high levels of CD1d, the restriction element for invariant natural killer T cells (iNKT). Here, we examined the effect of iNKT cells on MZB cell activation and numbers in vitro and in vivo in normal and autoimmune mice. Results show that iNKT cells activate MZBs, but restrict their numbers in vitro and in vivo in normal BALB/c and C57/BL6 mice. iNKT cells do so by increasing the activation-induced cell death and curtailing proliferation of MZB cells, whereas they promote the proliferation of follicular B cells. Sorted iNKT cells can directly execute this function, without help from other immune cells. Such MZB regulation by iNKTs is mediated, at least in part, via CD1d on B cells in a contact-dependent manner, whereas iNKT-induced proliferation of follicular B cells occurs in a contact- and CD1d-independent manner. Finally, we show that iNKT cells reduce 'autoreactive' MZB cells in an anti-DNA transgenic model, and limit MZB cell numbers in autoimmune-prone (NZB*NZW)F1 and non-obese diabetic mice, suggesting a potentially new mechanism whereby iNKT cells might regulate pathologic autoimmunity. Differential regulation of follicular B cells versus potentially autoreactive MZBs by iNKT cells has important implications for autoimmune diseases as well as for conditions that require a rapid innate B cell response. PMID- 22046305 TI - Peptide fingerprinting of Alzheimer's disease in cerebrospinal fluid: identification and prospective evaluation of new synaptic biomarkers. AB - BACKGROUND: Today, dementias are diagnosed late in the course of disease. Future treatments have to start earlier in the disease process to avoid disability requiring new diagnostic tools. The objective of this study is to develop a new method for the differential diagnosis and identification of new biomarkers of Alzheimer's disease (AD) using capillary-electrophoresis coupled to mass spectrometry (CE-MS) and to assess the potential of early diagnosis of AD. METHODS AND FINDINGS: Cerebrospinal fluid (CSF) of 159 out-patients of a memory clinic at a University Hospital suffering from neurodegenerative disorders and 17 cognitively-healthy controls was used to create differential peptide pattern for dementias and prospective blinded-comparison of sensitivity and specificity for AD diagnosis against the Criterion standard in a naturalistic prospective sample of patients. Sensitivity and specificity of the new method compared to standard diagnostic procedures and identification of new putative biomarkers for AD was the main outcome measure. CE-MS was used to reliably detect 1104 low-molecular weight peptides in CSF. Training-sets of patients with clinically secured sporadic Alzheimer's disease, frontotemporal dementia, and cognitively healthy controls allowed establishing discriminative biomarker pattern for diagnosis of AD. This pattern was already detectable in patients with mild cognitive impairment (MCI). The AD-pattern was tested in a prospective sample of patients (n = 100) and AD was diagnosed with a sensitivity of 87% and a specificity of 83%. Using CSF measurements of beta-amyloid1-42, total-tau, and phospho(181)-tau, AD-diagnosis had a sensitivity of 88% and a specificity of 67% in the same sample. Sequence analysis of the discriminating biomarkers identified fragments of synaptic proteins like proSAAS, apolipoprotein J, neurosecretory protein VGF, phospholemman, and chromogranin A. CONCLUSIONS: The method may allow early differential diagnosis of various dementias using specific peptide fingerprints and identification of incipient AD in patients suffering from MCI. Identified biomarkers facilitate face validity for the use in AD diagnosis. PMID- 22046306 TI - Expression of sympathetic nervous system genes in Lamprey suggests their recruitment for specification of a new vertebrate feature. AB - The sea lamprey is a basal, jawless vertebrate that possesses many neural crest derivatives, but lacks jaws and sympathetic ganglia. This raises the possibility that the factors involved in sympathetic neuron differentiation were either a gnathostome innovation or already present in lamprey, but serving different purposes. To distinguish between these possibilities, we isolated lamprey homologues of transcription factors associated with peripheral ganglion formation and examined their deployment in lamprey embryos. We further performed DiI labeling of the neural tube combined with neuronal markers to test if neural crest-derived cells migrate to and differentiate in sites colonized by sympathetic ganglia in jawed vertebrates. Consistent with previous anatomical data in adults, our results in lamprey embryos reveal that neural crest cells fail to migrate ventrally to form sympathetic ganglia, though they do form dorsal root ganglia adjacent to the neural tube. Interestingly, however, paralogs of the battery of transcription factors that mediate sympathetic neuron differentiation (dHand, Ascl1 and Phox2b) are present in the lamprey genome and expressed in various sites in the embryo, but fail to overlap in any ganglionic structures. This raises the intriguing possibility that they may have been recruited during gnathostome evolution to a new function in a neural crest derivative. PMID- 22046307 TI - Reversal of fragile X phenotypes by manipulation of AbetaPP/Abeta levels in Fmr1KO mice. AB - Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading known genetic cause of autism. Fragile X mental retardation protein (FMRP), which is absent or expressed at substantially reduced levels in FXS, binds to and controls the postsynaptic translation of amyloid beta protein precursor (AbetaPP) mRNA. Cleavage of AbetaPP can produce beta-amyloid (Abeta), a 39-43 amino acid peptide mis-expressed in Alzheimer's disease (AD) and Down syndrome (DS). Abeta is over-expressed in the brain of Fmr1(KO) mice, suggesting a pathogenic role in FXS. To determine if genetic reduction of AbetaPP/Abeta rescues characteristic FXS phenotypes, we assessed audiogenic seizures (AGS), anxiety, the ratio of mature versus immature dendritic spines and metabotropic glutamate receptor (mGluR)-mediated long-term depression (LTD) in Fmr1(KO) mice after removal of one App allele. All of these phenotypes were partially or completely reverted to normal. Plasma Abeta(1-42) was significantly reduced in full-mutation FXS males compared to age-matched controls while cortical and hippocampal levels were somewhat increased, suggesting that Abeta is sequestered in the brain. Evolving therapies directed at reducing Abeta in AD may be applicable to FXS and Abeta may serve as a plasma-based biomarker to facilitate disease diagnosis or assess therapeutic efficacy. PMID- 22046308 TI - A fresh insight into transmission of schistosomiasis: a misleading tale of Biomphalaria in Lake Victoria. AB - Lake Victoria is a known hot-spot for Schistosoma mansoni, which utilises freshwater snails of the genus Biomphalaria as intermediate hosts. Different species of Biomphalaria are associated with varying parasite compatibility, affecting local transmission. It is thought that two species, B. choanomphala and B. sudanica, inhabit Lake Victoria; despite their biomedical importance, the taxonomy of these species has not been thoroughly examined. This study combined analysis of morphological and molecular variables; the results demonstrated that molecular groupings were not consistent with morphological divisions. Habitat significantly predicted morphotype, suggesting that the different Lake Victorian forms of Biomphalaria are ecophentoypes of one species. The nomenclature should be revised accordingly; the names B. choanomphala choanomphala and B. c. sudanica are proposed. From a public health perspective, these findings can be utilised by policy-makers for better understanding of exposure risk, resulting in more effective and efficient control initiatives. PMID- 22046309 TI - Adverse events of interferon beta-1a: a prospective multi-centre international ICH-GCP-based CRO-supported external validation study in daily practice. AB - BACKGROUND: Due to methodological shortcomings the available post-registration data on the adverse events (AEs) occurring in interferon beta-1a (INFb-1a) treated patients fail to adequately validate phase III data and only partially inform on safety in daily practice. We assessed AEs in relapsing remitting multiple sclerosis (RRMS) patients treated with intramuscular (IM) INFb-1a in daily practice using data quality assurance measures similar to those in phase III trials. METHODS: A prospective, International Conference on Harmonization (ICH) - Good Clinical Practice (GCP)-based, clinical research organization (CRO) supported study in 36 practices in the Netherlands, Belgium, the United Kingdom and Luxembourg. During 24 months after start of IM INFb-1a treatment 275 RRMS patients were assessed for AEs' severity (mild, moderate, severe) and relationship to treatment (not, unlikely, likely, definite). Data were compared with those reported in the pivotal phase III trial. FINDINGS: 75.3% of the patients experienced one or more AEs that were likely or definitely related to INFb-1a. Of all AEs 40.5% were likely or definitely treatment-related; 68.5% of these were mild, and 3% severe. 6.6% of the patients discontinued treatment because of an AE. Compared to the pivotal phase III trial, we found statistically significantly lower incidences for most of the common AEs: headache, muscle ache, fatigue, fever, chills, nausea. One patient died following two cerebral vascular events in study month 22, both AEs were assessed as not related to INFb-1a. CONCLUSION: Three out of four RRMS patients treated with IM INFb-1a in daily practice experience treatment-related AEs, most of these being mild. Our data externally validate the favorable phase III safety profile of IM INFb-1a and suggest that the real-life incidence of treatment-related AEs is less than reported in the pivotal phase III trial. Larger studies are needed to detect rare, potentially hazardous AEs of IM INFb-1a. PMID- 22046310 TI - Evidence for positive selection on the leptin gene in Cetacea and Pinnipedia. AB - The leptin gene has received intensive attention and scientific investigation for its importance in energy homeostasis and reproductive regulation in mammals. Furthermore, study of the leptin gene is of crucial importance for public health, particularly for its role in obesity, as well as for other numerous physiological roles that it plays in mammals. In the present work, we report the identification of novel leptin genes in 4 species of Cetacea, and a comparison with 55 publicly available leptin sequences from mammalian genome assemblies and previous studies. Our study provides evidence for positive selection in the suborder Odontoceti (toothed whales) of the Cetacea and the family Phocidae (earless seals) of the Pinnipedia. We also detected positive selection in several leptin gene residues in these two lineages. To test whether leptin and its receptor evolved in a coordinated manner, we analyzed 24 leptin receptor gene (LPR) sequences from available mammalian genome assemblies and other published data. Unlike the case of leptin, our analyses did not find evidence of positive selection for LPR across the Cetacea and Pinnipedia lineages. In line with this, positively selected sites identified in the leptin genes of these two lineages were located outside of leptin receptor binding sites, which at least partially explains why co-evolution of leptin and its receptor was not observed in the present study. Our study provides interesting insights into current understanding of the evolution of mammalian leptin genes in response to selective pressures from life in an aquatic environment, and leads to a hypothesis that new tissue specificity or novel physiologic functions of leptin genes may have arisen in both odontocetes and phocids. Additional data from other species encompassing varying life histories and functional tests of the adaptive role of the amino acid changes identified in this study will help determine the factors that promote the adaptive evolution of the leptin genes in marine mammals. PMID- 22046311 TI - Exosomes from Plasmodium yoelii-infected reticulocytes protect mice from lethal infections. AB - Exosomes are 30-100-nm membrane vesicles of endocytic origin that are released after the fusion of multivesicular bodies (MVBs) with the plasma membrane. While initial studies suggested that the role of exosomes was limited to the removal of proteins during the maturation of reticulocytes to erythrocytes, recent studies indicate that they are produced by different types of cells and are involved in promoting inter-cellular communication and antigen presentation. Here, we describe the isolation and characterization of exosomes from peripheral blood of BALB/c mice infected with the reticulocyte-prone non-lethal Plasmodium yoelii 17X strain. Importantly, proteomic analysis revealed the presence of parasite proteins in these vesicles. Moreover, immunization of mice with purified exosomes elicited IgG antibodies capable of recognizing P. yoelii-infected red blood cells. Furthermore, lethal challenge of immunized mice with the normocyte-prone lethal P. yoelii 17XL strain caused a significant attenuation in the course of parasitaemia, increased survival time, and altered the cell tropism to reticulocytes. These results were obtained also when the exosomes were isolated from a P. yoelii-infected reticulocyte culture indicating that reticulocyte derived exosomes carry antigens and are involved in immune modulation. Moreover, inclusion of CpG ODN 1826 in exosome immunizations elicited IgG2a and IgG2b antibodies and promoted survival, clearance of parasites and subsequent sterile protection of 83% of the animals challenged with P. yoelli 17XL. To our knowledge, this is the first report of immune responses elicited by exosomes derived from reticulocytes opening new avenues for the modulation of anti-malaria responses. PMID- 22046312 TI - Efficient generation of fully reprogrammed human iPS cells via polycistronic retroviral vector and a new cocktail of chemical compounds. AB - Direct reprogramming of human somatic cells into induced pluripotent stem (iPS) cells by defined transcription factors (TFs) provides great potential for regenerative medicine and biomedical research. This procedure has many challenges, including low reprogramming efficiency, many partially reprogrammed colonies, somatic coding mutations in the genome, etc. Here, we describe a simple approach for generating fully reprogrammed human iPS cells by using a single polycistronic retroviral vector expressing four human TFs in a single open reading frame (ORF), combined with a cocktail containing three small molecules (Sodium butyrate, SB431542, and PD0325901). Our results demonstrate that human iPS cells generated by this approach express human ES cells markers and exhibit pluripotency demonstrated by their abilities to differentiate into the three germ layers in vitro and in vivo. Notably, this approach not only provides a much faster reprogramming process but also significantly diminishes partially reprogrammed iPS cell colonies, thus facilitating efficient isolation of desired fully reprogrammed iPS cell colonies. PMID- 22046313 TI - Social and nonsocial content differentially modulates visual attention and autonomic arousal in Rhesus macaques. AB - The sophisticated analysis of gestures and vocalizations, including assessment of their emotional valence, helps group-living primates efficiently navigate their social environment. Deficits in social information processing and emotion regulation are important components of many human psychiatric illnesses, such as autism, schizophrenia and social anxiety disorder. Analyzing the neurobiology of social information processing and emotion regulation requires a multidisciplinary approach that benefits from comparative studies of humans and animal models. However, many questions remain regarding the relationship between visual attention and arousal while processing social stimuli. Using noninvasive infrared eye-tracking methods, we measured the visual social attention and physiological arousal (pupil diameter) of adult male rhesus monkeys (Macaca mulatta) as they watched social and nonsocial videos. We found that social videos, as compared to nonsocial videos, captured more visual attention, especially if the social signals depicted in the videos were directed towards the subject. Subject directed social cues and nonsocial nature documentary footage, compared to videos showing conspecifics engaging in naturalistic social interactions, generated larger pupil diameters (indicating heightened sympathetic arousal). These findings indicate that rhesus monkeys will actively engage in watching videos of various kinds. Moreover, infrared eye tracking technology provides a mechanism for sensitively gauging the social interest of presented stimuli. Adult male rhesus monkeys' visual attention and physiological arousal do not always trend in the same direction, and are likely influenced by the content and novelty of a particular visual stimulus. This experiment creates a strong foundation for future experiments that will examine the neural network responsible for social information processing in nonhuman primates. Such studies may provide valuable information relevant to interpreting the neural deficits underlying human psychiatric illnesses such as autism, schizophrenia and social anxiety disorder. PMID- 22046314 TI - Pyomelanin formation in Aspergillus fumigatus requires HmgX and the transcriptional activator HmgR but is dispensable for virulence. AB - The opportunistic human pathogenic fungus Aspergillus fumigatus is able to produce the dark brown pigment pyomelanin by degradation of L-tyrosine. Pyomelanin was shown to protect the fungus against reactive oxygen intermediates as well as cell wall disturbing compounds and is therefore assumed to protect against immune effector cells during the infection process. Several genes for tyrosine degradation and pyomelanin formation are organized in a cluster in the genome of A. fumigatus. Here, we aimed at further analyzing tyrosine degradation and a possible role of pyomelanin in virulence. For this purpose, the function of two not yet characterized genes of the cluster, i.e., hmgX and hmgR, was analyzed. Generation of corresponding gene deletion mutants and reconstituted strains revealed that hmgX and hmgR are essential for tyrosine degradation. Both mutants, DeltahmgX and DeltahmgR, were not able to use tyrosine as sole carbon or nitrogen source and revealed impaired pyomelanin production. HmgR harbors a Zn(II)2Cys6-DNA binding domain. Analyses of the steady state mRNA levels revealed that HmgR acts as a transcriptional activator for the genes of the tyrosine degradation cluster. Consistently, an HmgR-eGFP fusion protein was localized in the nucleus of A. fumigatus cells. By contrast, HmgX was found to be localized in the cytoplasm and does not contribute to regulation of gene transcription. HPLC analyses showed that HmgX is crucial for the conversion of p hydroxyphenylpyruvate to homogentisic acid, the main intermediate in pyomelanin formation. Thus, HmgX is supposed to function as an accessory factor to mediate specific activity of HppD. Remarkably, the ability to degrade tyrosine and to form pyomelanin is dispensable for virulence of A. fumigatus in a murine infection model. PMID- 22046315 TI - Parallel evolution of KCNQ4 in echolocating bats. AB - High-frequency hearing is required for echolocating bats to locate, range and identify objects, yet little is known about its molecular basis. The discovery of a high-frequency hearing-related gene, KCNQ4, provides an opportunity to address this question. Here, we obtain the coding regions of KCNQ4 from 15 species of bats, including echolocating bats that have higher frequency hearing and non echolocating bats that have the same ability as most other species of mammals. The strongly supported protein-tree resolves a monophyletic group containing all bats with higher frequency hearing and this arrangement conflicts with the phylogeny of bats in which these species are paraphyletic. We identify five parallel evolved sites in echolocating bats belonging to both suborders. The evolutionary trajectories of the parallel sites suggest the independent gain of higher frequency hearing ability in echolocating bats. This study highlights the usefulness of convergent or parallel evolutionary studies for finding phenotype related genes and contributing to the resolution of evolutionary problems. PMID- 22046316 TI - Genetic variation of the IL-28B promoter affecting gene expression. AB - The current standard of care for the treatment of chronic hepatitis C is pegylated interferon-alpha (PEG-IFNalpha) and ribavirin (RBV). The treatment achieves a sustained viral clearance in only approximately 50% of patients. Recent whole genome association studies revealed that single nucleotide polymorphisms (SNPs) around IL-28B have been associated with response to the standard therapy and could predict treatment responses at approximately 80%. However, it is not clear which SNP is most informative because the genomic region containing significant SNPs shows strong linkage disequilibrium. We focused on SNPs in close proximity to the IL-28B gene to evaluate the function of each and identify the SNP affecting the IL-28B expression level most. The structures of IL 28A/B from 5' to 3'-UTR were determined by complete cDNA cloning. Both IL-28A and 28B genes consisted of 6 exons, differing from the CCDS data of NCBI. Two intron SNPs and a nonsynonymous SNP did not affect IL-28B gene function and expression levels but a SNP located in the proximal promoter region influenced gene expression. A (TA) dinucleotide repeat, rs72258881, located in the promoter region was discovered by our functional studies of the proximal SNPs upstream of IL-28B; the transcriptional activity of the promoter increased gradually in a (TA)(n) length-dependent manner following IFN-alpha and lipopolysaccharide stimulation. Healthy Japanese donors exhibited a broad range of (TA) dinucleotide repeat numbers from 10 to 18 and the most prevalent genotype was 12/12 (75%), differing from the database (13/13). However, genetic variation of IL-28A corresponding to that of IL-28B was not detected in these Japanese donors. These findings suggest that the dinucleotide repeat could be associated with the transcriptional activity of IL-28B as well as being a marker to improve the prediction of the response to interferon-based hepatitis C virus treatment. PMID- 22046317 TI - Control of bone resorption by semaphorin 4D is dependent on ovarian function. AB - Osteoporosis is one of the most common bone pathologies, which are characterized by a decrease in bone mass. It is well established that bone mass, which results from a balanced bone formation and bone resorption, is regulated by many hormonal, environmental and genetic factors. Here we report that the immune semaphorin 4D (Sema4D) is a novel factor controlling bone resorption. Sema4D deficient primary osteoclasts showed impaired spreading, adhesion, migration and resorption due to altered beta3 integrin sub-unit downstream signaling. In apparent accordance with these in vitro results, Sema4D deletion in sexually mature female mice led to a high bone mass phenotype due to defective bone resorption by osteoclasts. Mutant males, however, displayed normal bone mass and the female osteopetrotic phenotype was only detected at the onset of sexual maturity, indicating that, in vivo, this intrinsic osteoclast defect might be overcome in these mice. Using bone marrow cross transplantation, we confirmed that Sema4D controls bone resorption through an indirect mechanism. In addition, we show that Sema4D -/- mice were less fertile than their WT littermates. A decrease in Gnrh1 hypothalamic expression and a reduced number of ovarian follicles can explain this attenuated fertility. Interestingly, ovariectomy abrogated the bone resorption phenotype in Sema4D -/- mice, providing the evidence that the observed high bone mass phenotype is strictly dependent on ovarian function. Altogether, this study reveals that, in vivo, Sema4D is an indirect regulator of bone resorption, which acts via its effect on reproductive function. PMID- 22046318 TI - Quantitative proteomics reveals cellular targets of celastrol. AB - Celastrol, a natural substance isolated from plant extracts used in traditional Chinese medicine, has been extensively investigated as a possible drug for treatment of cancer, autoimmune diseases, and protein misfolding disorders. Although studies focusing on celastrol's effects in specific cellular pathways have revealed a considerable number of targets in a diverse array of in vitro models there is an essential need for investigations that can provide a global view of its effects. To assess cellular effects of celastrol and to identify target proteins as biomarkers for monitoring treatment regimes, we performed large-scale quantitative proteomics in cultured human lymphoblastoid cells, a cell type that can be readily prepared from human blood samples. Celastrol substantially modified the proteome composition and 158 of the close to 1800 proteins with robust quantitation showed at least a 1.5 fold change in protein levels. Up-regulated proteins play key roles in cytoprotection with a prominent group involved in quality control and processing of proteins traversing the endoplasmic reticulum. Increased levels of proteins essential for the cellular protection against oxidative stress including heme oxygenase 1, several peroxiredoxins and thioredoxins as well as proteins involved in the control of iron homeostasis were also observed. Specific analysis of the mitochondrial proteome strongly indicated that the mitochondrial association of certain antioxidant defense and apoptosis-regulating proteins increased in cells exposed to celastrol. Analysis of selected mRNA transcripts showed that celastrol activated several different stress response pathways and dose response studies furthermore showed that continuous exposure to sub-micromolar concentrations of celastrol is associated with reduced cellular viability and proliferation. The extensive catalog of regulated proteins presented here identifies numerous cellular effects of celastrol and constitutes a valuable biomarker tool for the development and monitoration of disease treatment strategies. PMID- 22046319 TI - Differential palmit(e)oylation of Wnt1 on C93 and S224 residues has overlapping and distinct consequences. AB - Though the mechanisms by which cytosolic/intracellular proteins are regulated by the post-translational addition of palmitate adducts is well understood, little is known about how this lipid modification affects secreted ligands, such as Wnts. Here we use mutational analysis to show that differential modification of the two known palmit(e)oylated residues of Wnt1, C93 and S224, has both overlapping and distinct consequences. Though the relative roles of each residue are similar with respect to stability and secretion, two distinct biological assays in L cells show that modification of C93 primarily modulates signaling via a beta-catenin independent pathway while S224 is crucial for beta-catenin dependent signaling. In addition, pharmacological inhibition of Porcupine (Porcn), an upstream regulator of Wnt, by IWP1, specifically inhibited beta catenin dependent signaling. Consistent with these observations, mapping of amino acids in peptide domains containing C93 and S224 demonstrate that acylation of C93 is likely to be Porcn-independent while that of S224 is Porcn-dependent. Cumulatively, our data strongly suggest that C93 and S224 are modified by distinct enzymes and that the differential modification of these sites has the potential to influence Wnt signaling pathway choice. PMID- 22046320 TI - An alignment-free approach for eukaryotic ITS2 annotation and phylogenetic inference. AB - The ITS2 gene class shows a high sequence divergence among its members that have complicated its annotation and its use for reconstructing phylogenies at a higher taxonomical level (beyond species and genus). Several alignment strategies have been implemented to improve the ITS2 annotation quality and its use for phylogenetic inferences. Although, alignment based methods have been exploited to the top of its complexity to tackle both issues, no alignment-free approaches have been able to successfully address both topics. By contrast, the use of simple alignment-free classifiers, like the topological indices (TIs) containing information about the sequence and structure of ITS2, may reveal to be a useful approach for the gene prediction and for assessing the phylogenetic relationships of the ITS2 class in eukaryotes. Thus, we used the TI2BioP (Topological Indices to BioPolymers) methodology [1], [2], freely available at http://ti2biop.sourceforge.net/ to calculate two different TIs. One class was derived from the ITS2 artificial 2D structures generated from DNA strings and the other from the secondary structure inferred from RNA folding algorithms. Two alignment-free models based on Artificial Neural Networks were developed for the ITS2 class prediction using the two classes of TIs referred above. Both models showed similar performances on the training and the test sets reaching values above 95% in the overall classification. Due to the importance of the ITS2 region for fungi identification, a novel ITS2 genomic sequence was isolated from Petrakia sp. This sequence and the test set were used to comparatively evaluate the conventional classification models based on multiple sequence alignments like Hidden Markov based approaches, revealing the success of our models to identify novel ITS2 members. The isolated sequence was assessed using traditional and alignment-free based techniques applied to phylogenetic inference to complement the taxonomy of the Petrakia sp. fungal isolate. PMID- 22046321 TI - Improved adsorption of an Enterococcus faecalis bacteriophage PhiEF24C with a spontaneous point mutation. AB - Some bacterial strains of the multidrug-resistant Gram-positive bacteria Enterococcus faecalis can significantly reduce the efficacy of conventional antimicrobial chemotherapy. Thus, the introduction of bacteriophage (phage) therapy is expected, where a phage is used as a bioagent to destroy bacteria. E. faecalis phage PhiEF24C is known to be a good candidate for a therapeutic phage against E. faecalis. However, this therapeutic phage still produces nonuniform antimicrobial effects with different bacterial strains of the same species and this might prove detrimental to its therapeutic effects. One solution to this problem is the preparation of mutant phages with higher activity, based on a scientific rationale. This study isolated and analyzed a spontaneous mutant phage, PhiEF24C-P2, which exhibited higher infectivity against various bacterial strains when compared with phage PhiEF24C. First, the improved bactericidal effects of phage PhiEF24C-P2 were attributable to its increased adsorption rate. Moreover, genomic sequence scanning revealed that phage PhiEF24C-P2 had a point mutation in orf31. Proteomic analysis showed that ORF31 (mw, 203 kDa) was present in structural components, and immunological analysis using rabbit-derived antibodies showed that it was a component of a long, flexible fine tail fiber extending from the tail end. Finally, phage PhiEF24C-P2 also showed higher bactericidal activity in human blood compared with phage PhiEF24C using the in vitro assay system. In conclusion, the therapeutic effects of phage PhiEF24C-P2 were improved by a point mutation in gene orf31, which encoded a tail fiber component. PMID- 22046322 TI - Protective effects of white button mushroom (Agaricus bisporus) against hepatic steatosis in ovariectomized mice as a model of postmenopausal women. AB - Nonalcoholic fatty liver disease (NAFLD) includes various hepatic pathologies ranging from hepatic steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Estrogen provides a protective effect on the development of NAFLD in women. Therefore, postmenopausal women have a higher risk of developing NAFLD. Hepatic steatosis is an early stage of fatty liver disease. Steatosis can develop to the aggressive stages (nonalcoholic steatohepatitis, fibrosis and cirrhosis). Currently, there is no specific drug to prevent/treat these liver diseases. In this study, we found that white button mushroom (WBM), Agaricus Bisporus, has protective effects against liver steatosis in ovariectomized (OVX) mice (a model of postmenopausal women). OVX mice were fed a high fat diet supplemented with WBM powder. We found that dietary WBM intake significantly lowered liver weight and hepatic injury markers in OVX mice. Pathological examination of liver tissue showed less fat accumulation in the livers of mice on WBM diet; moreover, these animals had improved glucose clearance ability. Microarray analysis revealed that genes related to the fatty acid biosynthesis pathway, particularly the genes for fatty acid synthetase (Fas) and fatty acid elongase 6 (Elovl6), were down regulated in the liver of mushroom-fed mice. In vitro mechanistic studies using the HepG2 cell line showed that down-regulation of the expression of FAS and ELOVL6 by WBM extract was through inhibition of Liver X receptor (LXR) signaling and its downstream transcriptional factor SREBP1c. These results suggest that WBM is protective against hepatic steatosis and NAFLD in OVX mice as a model for postmenopausal women. PMID- 22046323 TI - Paromomycin affects translation and vesicle-mediated trafficking as revealed by proteomics of paromomycin -susceptible -resistant Leishmania donovani. AB - Leishmania donovani is a protozoan parasite that causes visceral leishmaniasis (VL) and is responsible for significant mortality and morbidity. Increasing resistance towards antimonial drugs poses a great challenge in chemotherapy of VL. Paromomycin is an aminoglycosidic antibiotic and is one of the drugs currently being used in the chemotherapy of cutaneous and visceral leishmaniasis. To understand the mode of action of this antibiotic at the molecular level, we have investigated the global proteome differences between the wild type AG83 strain and a paromomycin resistant (PRr) strain of L. donovani. Stable isotope labeling of amino acids in cell culture (SILAC) followed by quantitative mass spectrometry of the wild type AG83 strain and the paromomycin resistant (PRr) strain identified a total of 226 proteins at >= 95% confidence. Data analysis revealed upregulation of 29 proteins and down-regulation of 21 proteins in the PRr strain. Comparative proteomic analysis of the wild type and the paromomycin resistant strains showed upregulation of the ribosomal proteins in the resistant strain indicating role in translation. Elevated levels of glycolytic enzymes and stress proteins were also observed in the PRr strain. Most importantly, we observed upregulation of proteins that may have a role in intracellular survival and vesicular trafficking in the PRr strain. Furthermore, ultra-structural analysis by electron microscopy demonstrated increased number of vesicular vacuoles in PRr strain when compared to the wild-type strain. Drug affinity pull down assay followed by mass spectrometery identified proteins in L. donovani wild type strain that were specifically and covalently bound to paromomycin. These results provide the first comprehensive insight into the mode of action and underlying mechanism of resistance to paromomycin in Leishmania donovani. PMID- 22046324 TI - Characterization of protection afforded by a bivalent virus-like particle vaccine against bluetongue virus serotypes 1 and 4 in sheep. AB - BACKGROUND: Bluetongue virus (BTV) is an economically important, arthropod borne, emerging pathogen in Europe, causing disease mainly in sheep and cattle. Routine vaccination for bluetongue would require the ability to distinguish between vaccinated and infected individuals (DIVA). Current vaccines are effective but are not DIVA. Virus-like particles (VLPs) are highly immunogenic structural mimics of virus particles, that only contain a subset of the proteins present in a natural infection. VLPs therefore offer the potential for the development of DIVA compatible bluetongue vaccines. METHODOLOGY/PRINCIPAL FINDINGS: Merino sheep were vaccinated with either monovalent BTV-1 VLPs or a bivalent mixture of BTV-1 VLPs and BTV-4 VLPs, and challenged with virulent BTV-1 or BTV-4. Animals were monitored for clinical signs, antibody responses, and viral RNA. 19/20 animals vaccinated with BTV-1 VLPs either alone or in combination with BTV-4 VLPs developed neutralizing antibodies to BTV-1, and group specific antibodies to BTV VP7. The one animal that showed no detectable neutralizing antibodies, or group specific antibodies, had detectable viral RNA following challenge but did not display any clinical signs on challenge with virulent BTV-1. In contrast, all control animals' demonstrated classical clinical signs for bluetongue on challenge with the same virus. Six animals were vaccinated with bivalent vaccine and challenged with virulent BTV-4, two of these animals had detectable viral levels of viral RNA, and one of these showed clinical signs consistent with BTV infection and died. CONCLUSIONS: There is good evidence that BTV-1 VLPs delivered as monovalent or bivalent immunogen protect from bluetongue disease on challenge with virulent BTV-1. However, it is possible that there is some interference in protective response for BTV-4 in the bivalent BTV-1 and BTV-4 VLP vaccine. This raises the question of whether all combinations of bivalent BTV vaccines are possible, or if immunodominance of particular serotypes could interfere with vaccine efficacy. PMID- 22046325 TI - A short-term physical activity randomized trial in the Lower Mississippi Delta. AB - BACKGROUND: The purpose of this study was to determine if a short-term pedometer based intervention results in immediate increases in time spent in moderate-to vigorous physical activity (MVPA) compared to a minimal educational intervention. METHODS: A sample of 43 overweight adults 35 to 64 years of age participated in a one week pedometer-based feasibility trial monitored by accelerometry. Participants were randomized into a one-week education-only group or a group that also wore a pedometer. Accelerometer-measured MVPA was measured over 7 days at baseline and again for 7 days immediately post-intervention. RESULTS: Minutes of MVPA increased significantly in the overall sample (p = 0.02); however, the effect of adding the pedometer to the education program was not significant (p = 0.89). Mean (+/-SE) MVPA increased from 12.7 +/- 2.4 min/day to 16.2 +/- 3.6 min/day in the education-only group and from 13.2 +/- 3.3 min/day to 16.3 +/- 3.9 min/day in the education+pedometer group. The correlation between change in steps/day and change in MVPA was 0.69 (p<0.0001). CONCLUSIONS: The results of this study suggest that the addition of a pedometer to a short-term education program does not produce added benefits with respect to increasing physical activity in the Lower Mississippi Delta. TRIAL REGISTRATION: ClinicalTrials.gov NCT01264757. PMID- 22046326 TI - 'Smoking genes': a genetic association study. AB - Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1*2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (-48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2 ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of variant alleles, the odds ratio (OR) for being a non-smoker in individuals with the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P<=0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1*2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1). PMID- 22046327 TI - Size-specific tree mortality varies with neighbourhood crowding and disturbance in a Montane Nothofagus forest. AB - Tree mortality is a fundamental process governing forest dynamics, but understanding tree mortality patterns is challenging because large, long-term datasets are required. Describing size-specific mortality patterns can be especially difficult, due to few trees in larger size classes. We used permanent plot data from Nothofagus solandri var. cliffortioides (mountain beech) forest on the eastern slopes of the Southern Alps, New Zealand, where the fates of trees on 250 plots of 0.04 ha were followed, to examine: (1) patterns of size-specific mortality over three consecutive periods spanning 30 years, each characterised by different disturbance, and (2) the strength and direction of neighbourhood crowding effects on size-specific mortality rates. We found that the size specific mortality function was U-shaped over the 30-year period as well as within two shorter periods characterised by small-scale pinhole beetle and windthrow disturbance. During a third period, characterised by earthquake disturbance, tree mortality was less size dependent. Small trees (<20 cm in diameter) were more likely to die, in all three periods, if surrounded by a high basal area of larger neighbours, suggesting that size-asymmetric competition for light was a major cause of mortality. In contrast, large trees (>= 20 cm in diameter) were more likely to die in the first period if they had few neighbours, indicating that positive crowding effects were sometimes important for survival of large trees. Overall our results suggest that temporal variability in size specific mortality patterns, and positive interactions between large trees, may sometimes need to be incorporated into models of forest dynamics. PMID- 22046328 TI - Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion. AB - BACKGROUND: Secretion of insulin and glucagon is triggered by elevated intracellular calcium levels. Although the precise mechanism by which the calcium signal is coupled to insulin and glucagon granule exocytosis is unclear, synaptotagmin-7 has been shown to be a positive regulator of calcium-dependent insulin and glucagon secretion, and may function as a calcium sensor for insulin and glucagon granule exocytosis. Deletion of synaptotagmin-7 leads to impaired glucose-stimulated insulin secretion and nearly abolished Ca(2+)-dependent glucagon secretion in mice. Under non-stressed resting state, however, synaptotagmin-7 KO mice exhibit normal insulin level but severely reduced glucagon level. METHODOLOGY/PRINCIPAL FINDINGS: We studied energy expenditure and metabolism in synaptotagmin-7 KO and control mice using indirect calorimetry and biochemical techniques. Synaptotagmin-7 KO mice had lower body weight and body fat content, and exhibited higher oxygen consumption and basal metabolic rate. Respiratory exchange ratio (RER) was lower in synaptotagmin-7 KO mice, suggesting an increased use of lipid in their energy production. Consistent with lower RER, gene expression profiles suggest enhanced lipolysis and increased capacity for fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore, expression of uncoupling protein 3 (UCP3) in skeletal muscle was approximately doubled in the KO mice compared with control mice. CONCLUSIONS: These results show that the lean phenotype in synaptotagmin-7 KO mice was mostly attributed to increased lipolysis and energy expenditure, and suggest that reduced glucagon level may have broad influence on the overall metabolism in the mouse model. PMID- 22046329 TI - The role of geomagnetic cues in green turtle open sea navigation. AB - BACKGROUND: Laboratory and field experiments have provided evidence that sea turtles use geomagnetic cues to navigate in the open sea. For instance, green turtles (Chelonia mydas) displaced 100 km away from their nesting site were impaired in returning home when carrying a strong magnet glued on the head. However, the actual role of geomagnetic cues remains unclear, since magnetically treated green turtles can perform large scale (>2000 km) post-nesting migrations no differently from controls. METHODOLOGY/PRINCIPAL FINDINGS: In the present homing experiment, 24 green turtles were displaced 200 km away from their nesting site on an oceanic island, and tracked, for the first time in this type of experiment, with Global Positioning System (GPS), which is able to provide much more frequent and accurate locations than previously used tracking methods. Eight turtles were magnetically treated for 24-48 h on the nesting beach prior to displacement, and another eight turtles had a magnet glued on the head at the release site. The last eight turtles were used as controls. Detailed analyses of water masses-related (i.e., current-corrected) homing paths showed that magnetically treated turtles were able to navigate toward their nesting site as efficiently as controls, but those carrying magnets were significantly impaired once they arrived within 50 km of home. CONCLUSIONS/SIGNIFICANCE: While green turtles do not seem to need geomagnetic cues to navigate far from the goal, these cues become necessary when turtles get closer to home. As the very last part of the homing trip (within a few kilometers of home) likely depends on non-magnetic cues, our results suggest that magnetic cues play a key role in sea turtle navigation at an intermediate scale by bridging the gap between large and small scale navigational processes, which both appear to depend on non-magnetic cues. PMID- 22046330 TI - Dab1 (Disable homolog-1) reelin adaptor protein is overexpressed in the olfactory bulb at early postnatal stages. AB - Dab1 mediates reelin signalling and plays critical roles in early brain development such as the stereotypical positioning of neurons in the brain. The olfactory bulb undergoes a prominent layering reorganization, but shows not apparent differences between wild type and reeler in the layer organization. Therefore, an accurate regional and cellular simultaneous analysis of these molecules becomes essential to clarify the role played by Dab1 upon Reelin effect. The present study reveals a strong and consistent Dab1 mRNA and protein expressions, throughout the olfactory bulb layers in both wild type and reeler mice. In addition, noteworthy is the pattern of Dab1 location within cell nuclei in both strains. Furthermore, a temporal increment of Dab1 expression levels is detected from P0 to P15 in both strains, being the protein quantity higher in reeler than in wild type mice. Altogether, our results revealed that Reln acts directly from projection neurons via the production of different Reln fragments. Changes in the pattern of Dab1 expression could reflect an alternative Reln function in postnatal and adult stages, besides a possible regulation of Dab1 by other molecules distinct to Reln. PMID- 22046331 TI - Sialome of a generalist lepidopteran herbivore: identification of transcripts and proteins from Helicoverpa armigera labial salivary glands. AB - Although the importance of insect saliva in insect-host plant interactions has been acknowledged, there is very limited information on the nature and complexity of the salivary proteome in lepidopteran herbivores. We inspected the labial salivary transcriptome and proteome of Helicoverpa armigera, an important polyphagous pest species. To identify the majority of the salivary proteins we have randomly sequenced 19,389 expressed sequence tags (ESTs) from a normalized cDNA library of salivary glands. In parallel, a non-cytosolic enriched protein fraction was obtained from labial salivary glands and subjected to two dimensional gel electrophoresis (2-DE) and de novo peptide sequencing. This procedure allowed comparison of peptides and EST sequences and enabled us to identify 65 protein spots from the secreted labial saliva 2DE proteome. The mass spectrometry analysis revealed ecdysone, glucose oxidase, fructosidase, carboxyl/cholinesterase and an uncharacterized protein previously detected in H. armigera midgut proteome. Consistently, their corresponding transcripts are among the most abundant in our cDNA library. We did find redundancy of sequence identification of saliva-secreted proteins suggesting multiple isoforms. As expected, we found several enzymes responsible for digestion and plant offense. In addition, we identified non-digestive proteins such as an arginine kinase and abundant proteins of unknown function. This identification of secreted salivary gland proteins allows a more comprehensive understanding of insect feeding and poses new challenges for the elucidation of protein function. PMID- 22046332 TI - High-throughput assay for the identification of compounds regulating osteogenic differentiation of human mesenchymal stromal cells. AB - Human mesenchymal stromal cells are regarded as the golden standard for cell based therapies. They present multilineage differentiation potential and trophic and immunosuppressive abilities, making them the best candidate for clinical applications. Several molecules have been described to increase bone formation and were mainly discovered by candidate approaches towards known signaling pathways controlling osteogenesis. However, their bone forming potential is still limited, making the search for novel molecules a necessity. High-throughput screening (HTS) not only allows the screening of a large number of diverse chemical compounds, but also allows the discovery of unexpected signaling pathways and molecular mechanisms for a certain application, even without the prior knowledge of the full molecular pathway. Typically HTS is performed in cell lines, however, in this manuscript we have performed a phenotypical screen on more clinically relevant human mesenchymal stromal cells, as a proof of principle that HTS can be performed in those cells and can be used to find small molecules that impact stem cell fate. From a library of pharmacologically active small molecules, we were able to identify novel compounds with increased osteogenic activity. These compounds allowed achieving levels of bone-specific alkaline phosphatase higher than any other combination previously known. By combining biochemical techniques, we were able to demonstrate that a medium to high throughput phenotypic assay can be performed in academic research laboratories allowing the discovery of novel molecules able to enhance stem cell differentiation. PMID- 22046333 TI - Development by design: mitigating wind development's impacts on wildlife in Kansas. AB - Wind energy, if improperly sited, can impact wildlife through direct mortality and habitat loss and fragmentation, in contrast to its environmental benefits in the areas of greenhouse gas, air quality, and water quality. Fortunately, risks to wildlife from wind energy may be alleviated through proper siting and mitigation offsets. Here we identify areas in Kansas where wind development is incompatible with conservation, areas where wind development may proceed but with compensatory mitigation for impacts, and areas where development could proceed without the need for compensatory mitigation. We demonstrate that approximately 10.3 million ha in Kansas (48 percent of the state) has the potential to provide 478 GW of installed capacity while still meeting conservation goals. Of this total, approximately 2.7 million ha would require no compensatory mitigation and could produce up to 125 GW of installed capacity. This is 1,648 percent higher than the level of wind development needed in Kansas by 2030 if the United States is to get 20 percent of its electricity from wind. Projects that avoid and offset impacts consistent with this analysis could be awarded "Green Certification." Certification may help to expand and sustain the wind industry by facilitating the completion of individual projects sited to avoid sensitive areas and protecting the industry's reputation as an ecologically friendly source of electricity. PMID- 22046334 TI - Individual differences in impulsivity predict anticipatory eye movements. AB - Impulsivity is the tendency to act without forethought. It is a personality trait commonly used in the diagnosis of many psychiatric diseases. In clinical practice, impulsivity is estimated using written questionnaires. However, answers to questions might be subject to personal biases and misinterpretations. In order to alleviate this problem, eye movements could be used to study differences in decision processes related to impulsivity. Therefore, we investigated correlations between impulsivity scores obtained with a questionnaire in healthy subjects and characteristics of their anticipatory eye movements in a simple smooth pursuit task. Healthy subjects were asked to answer the UPPS questionnaire (Urgency Premeditation Perseverance and Sensation seeking Impulsive Behavior scale), which distinguishes four independent dimensions of impulsivity: Urgency, lack of Premeditation, lack of Perseverance, and Sensation seeking. The same subjects took part in an oculomotor task that consisted of pursuing a target that moved in a predictable direction. This task reliably evoked anticipatory saccades and smooth eye movements. We found that eye movement characteristics such as latency and velocity were significantly correlated with UPPS scores. The specific correlations between distinct UPPS factors and oculomotor anticipation parameters support the validity of the UPPS construct and corroborate neurobiological explanations for impulsivity. We suggest that the oculomotor approach of impulsivity put forth in the present study could help bridge the gap between psychiatry and physiology. PMID- 22046335 TI - Tracking traders' understanding of the market using e-communication data. AB - Tracking the volume of keywords in Internet searches, message boards, or Tweets has provided an alternative for following or predicting associations between popular interest or disease incidences. Here, we extend that research by examining the role of e-communications among day traders and their collective understanding of the market. Our study introduces a general method that focuses on bundles of words that behave differently from daily communication routines, and uses original data covering the content of instant messages among all day traders at a trading firm over a 40-month period. Analyses show that two word bundles convey traders' understanding of same day market events and potential next day market events. We find that when market volatility is high, traders' communications are dominated by same day events, and when volatility is low, communications are dominated by next day events. We show that the stronger the traders' attention to either same day or next day events, the higher their collective trading performance. We conclude that e-communication among traders is a product of mass collaboration over diverse viewpoints that embodies unique information about their weak or strong understanding of the market. PMID- 22046336 TI - Assessing the dream-lag effect for REM and NREM stage 2 dreams. AB - This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events and memories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurred in waking life, or, more often, they can be partial or indirect. Two types of temporal relationship have been found to characterize the time of occurrence of a daytime event and the reappearance or incorporation of its features in a dream. These temporal relationships are referred to as the day residue or immediate incorporation effect, where there is the reappearance of features from events occurring on the immediately preceding day, and the dream lag effect, where there is the reappearance of features from events occurring 5-7 days prior to the dream. Previous work on the dream-lag effect has used spontaneous home recalled dream reports, which can be from Rapid Eye Movement Sleep (REM) and from non-Rapid Eye Movement Sleep (NREM). This study addresses whether the dream-lag effect occurs only for REM sleep dreams, or for both REM and NREM stage 2 (N2) dreams. 20 participants kept a daily diary for over a week before sleeping in the sleep laboratory for 2 nights. REM and N2 dreams collected in the laboratory were transcribed and each participant rated the level of correspondence between every dream report and every diary record. The dream-lag effect was found for REM but not N2 dreams. Further analysis indicated that this result was not due to N2 dream reports being shorter, in terms of number of words, than the REM dream reports. These results provide evidence for a 7-day sleep-dependent non-linear memory consolidation process that is specific to REM sleep, and accord with proposals for the importance of REM sleep to emotional memory consolidation. PMID- 22046337 TI - Role of the primary motor cortex in the early boost in performance following mental imagery training. AB - Recently, it has been suggested that the primary motor cortex (M1) plays a critical role in implementing the fast and transient post-training phase of motor skill consolidation, known to yield an early boost in performance. Whether a comparable early boost in performance occurs following motor imagery (MIM) training is still unknown. To address this issue, two groups of subjects learned a finger tapping sequence either by MIM or physical practice (PP). In both groups, performance increased significantly in the post-training phase when compared with the pre-training phase and further increased after a 30 min resting period, indicating that both MIM and PP trainings were equally efficient and induced an early boost in motor performance. This conclusion was corroborated by the results of an additional control group. In a second experiment, we then investigated the causal role of M1 in implementing the early boost process resulting from MIM training. To do so, we inhibited M1 by applying a continuous theta-burst stimulation (cTBS) in healthy volunteers just after they learnt, by MIM, the same finger-tapping task as in Experiment #1. As a control, cTBS was applied over the vertex of subjects who underwent the same experiment. We found that cTBS applied over M1 selectively abolished the early boost process subsequent to MIM training. Altogether, the present study provides evidence that MIM practice induces an early boost in performance and demonstrates that M1 is causally involved in this process. These findings further divulge some degree of behavioral and neuronal similitude between MIM and PP. PMID- 22046338 TI - An in vivo platform for tumor biomarker assessment. AB - Tumor biomarkers provide a quantitative tool for following tumor progression and response to therapy. However, investigations of clinically useful tumor biomarkers are time-consuming, costly, and limited by patient and tumor heterogeneity. In addition, assessment of biomarkers as indicators of therapy response is confounded by the concomitant use of multiple therapeutic interventions. Herein we report our use of a clinically relevant orthotopic animal model of malignant pleural mesothelioma for investigating tumor biomarkers. Utilizing multi-modality imaging with correlative histopathology, we demonstrate the utility and accuracy of the mouse model in investigating tumor biomarkers--serum soluble mesothelin-related peptide (SMRP) and osteopontin (OPN). This model revealed percentage change in SMRP level to be an accurate biomarker of tumor progression and therapeutic response--a finding consistent with recent clinical studies. This in vivo platform demonstrates the advantages of a validated mouse model for the timely and cost-effective acceleration of human biomarker translational research. PMID- 22046339 TI - Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model. AB - BACKGROUND: A reduction in cochlear blood flow plays an essential role in noise induced hearing loss (NIHL). The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2)S) has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2)S in cochlear blood flow regulation and noise protection. METHODOLOGY/PRINCIPAL FINDINGS: The gene and protein expression of the H(2)S synthetase cystathionine-gamma-lyase (CSE) in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP), NaHS or DL propargylglycine (PPG) were locally administered. Local sodium hydrosulfide (NaHS) significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR), cochlear scanning electron microscope (SEM) and outer hair cell (OHC) count. The highest percentage of OHC loss occurred in the PPG group. CONCLUSIONS/SIGNIFICANCE: Our results suggest that H(2)S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases. PMID- 22046340 TI - Exploring the diversity of Gardnerella vaginalis in the genitourinary tract microbiota of monogamous couples through subtle nucleotide variation. AB - BACKGROUND: Bacterial vaginosis (BV) is an enigmatic disease of unknown origin that affects a large percentage of women. The vaginal microbiota of women with BV is associated with serious sequelae, including abnormal pregnancies. The etiology of BV is not fully understood, however, it has been suggested that it is transmissible, and that G. vaginalis may be an etiological agent. Studies using enzymatic assays to define G. vaginalis biotypes, as well as more recent genomic comparisons of G. vaginalis isolates from symptomatic and asymptomatic women, suggest that particular G. vaginalis strains may play a key role in the pathogenesis of BV. METHODOLOGY/PRINCIPAL FINDINGS: To explore G. vaginalis diversity, distribution and sexual transmission, we developed a Shannon entropy based method to analyze low-level sequence variation in 65,710 G. vaginalis 16S rRNA gene segments that were PCR-amplified from vaginal samples of 53 monogamous women and from urethral and penile skin samples of their male partners. We observed a high degree of low-level diversity among G. vaginalis sequences with a total of 46 unique sequence variants (oligotypes), and also found strong correlations of these oligotypes between sexual partners. Even though Gram stain defined normal and some Gram stain-defined intermediate oligotype profiles clustered together in UniFrac analysis, no single G. vaginalis oligotype was found to be specific to BV or normal vaginal samples. CONCLUSIONS: This study describes a novel method for investigating G. vaginalis diversity at a low level of taxonomic discrimination. The findings support cultivation-based studies that indicate sexual partners harbor the same strains of G. vaginalis. This study also highlights the fact that a few, reproducible nucleotide variations within the 16S rRNA gene can reveal clinical or epidemiological associations that would be missed by genus-level or species-level categorization of 16S rRNA data. PMID- 22046341 TI - Selective algicidal action of peptides against harmful algal bloom species. AB - Recently, harmful algal bloom (HAB), also termed "red tide", has been recognized as a serious problem in marine environments according to climate changes worldwide. Many novel materials or methods to prevent HAB have not yet been employed except for clay dispersion, in which can the resulting sedimentation on the seafloor can also cause alteration in marine ecology or secondary environmental pollution. In the current study, we investigated that antimicrobial peptide have a potential in controlling HAB without cytotoxicity to harmless marine organisms. Here, antimicrobial peptides are proposed as new algicidal compounds in combating HAB cells. HPA3 and HPA3NT3 peptides which exert potent antimicrobial activity via pore forming action in plasma membrane showed that HPA3NT3 reduced the motility of algal cells, disrupted their plasma membrane, and induced the efflux of intracellular components. Against raphidoflagellate such as Heterosigma akashiwo, Chattonella sp., and C. marina, it displayed a rapid lysing action in cell membranes at 1~4 uM within 2 min. Comparatively, its lysing effects occurred at 8 uM within 1 h in dinoflagellate such as Cochlodium polykrikoides, Prorocentrum micans, and P. minimum. Moreover, its lysing action induced the lysis of chloroplasts and loss of chlorophyll a. In the contrary, this peptide was not effective against Skeletonema costatum, harmless algal cell, even at 256 uM, moreover, it killed only H. akashiwo or C. marina in co cultivation with S. costatum, indicating to its selective algicidal activity between harmful and harmless algal cells. The peptide was non-hemolytic against red blood cells of Sebastes schlegeli, the black rockfish, at 120 uM. HAB cells were quickly and selectively lysed following treatment of antimicrobial peptides without cytotoxicity to harmless marine organisms. Thus, the antibiotic peptides examined in our study appear to have much potential in effectively controlling HAB with minimal impact on marine ecology. PMID- 22046342 TI - The CDKN2A G500 allele is more frequent in GBM patients with no defined telomere maintenance mechanism tumors and is associated with poorer survival. AB - Prognostic markers for glioblastoma multiforme (GBM) are important for patient management. Recent advances have identified prognostic markers for GBMs that use telomerase or the alternative lengthening of telomeres (ALT) mechanism for telomere maintenance. Approximately 40% of GBMs have no defined telomere maintenance mechanism (NDTMM), with a mixed survival for affected individuals. This study examined genetic variants in the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene that encodes the p16(INK4a) and p14(ARF) tumor suppressors, and the isocitrate dehydrogenase 1 (IDH1) gene as potential markers of survival for 40 individuals with NDTMM GBMs (telomerase negative and ALT negative by standard assays), 50 individuals with telomerase, and 17 individuals with ALT positive tumors. The analysis of CDKN2A showed NDTMM GBMs had an increased minor allele frequency for the C500G (rs11515) polymorphism compared to those with telomerase and ALT positive GBMs (p = 0.002). Patients with the G500 allele had reduced survival that was independent of age, extent of surgery, and treatment. In the NDTMM group G500 allele carriers had increased loss of CDKN2A gene dosage compared to C500 homozygotes. An analysis of IDH1 mutations showed the R132H mutation was associated with ALT positive tumors, and was largely absent in NDTMM and telomerase positive tumors. In the ALT positive tumors cohort, IDH1 mutations were associated with a younger age for the affected individual. In conclusion, the G500 CDKN2A allele was associated with NDTMM GBMs from older individuals with poorer survival. Mutations in IDH1 were not associated with NDTMM GBMs, and instead were a marker for ALT positive tumors in younger individuals. PMID- 22046343 TI - A broad set of different llama antibodies specific for a 16 kDa heat shock protein of Mycobacterium tuberculosis. AB - BACKGROUND: Recombinant antibodies are powerful tools in engineering of novel diagnostics. Due to the small size and stable nature of llama antibody domains selected antibodies can serve as a detection reagent in multiplexed and sensitive assays for M. tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Antibodies for Mycobacterium tuberculosis (M. tb) recognition were raised in Alpaca, and, by phage display, recombinant variable domains of heavy-chain antibodies (VHH) binding to M. tuberculosis antigens were isolated. Two phage display selection strategies were followed: one direct selection using semi-purified protein antigen, and a depletion strategy with lysates, aiming to avoid cross-reaction to other mycobacteria. Both panning methods selected a set of binders with widely differing complementarity determining regions. Selected recombinant VHHs were produced in E. coli and shown to bind immobilized lysate in direct Enzymelinked Immunosorbent Assay (ELISA) tests and soluble antigen by surface plasmon resonance (SPR) analysis. All tested VHHs were specific for tuberculosis-causing mycobacteria (M. tuberculosis, M. bovis) and exclusively recognized an immunodominant 16 kDa heat shock protein (hsp). The highest affinity VHH had a dissociation constant (KD) of 4 * 10(-10) M. CONCLUSIONS/SIGNIFICANCE: A broad set of different llama antibodies specific for 16 kDa heat shock protein of M. tuberculosis is available. This protein is highly stable and abundant in M. tuberculosis. The VHH that detect this protein are applied in a robust SPR sensor for identification of tuberculosis-causing mycobacteria. PMID- 22046344 TI - The role of endosomal escape and mitogen-activated protein kinases in adenoviral activation of the innate immune response. AB - Adenoviral vectors (AdV) activate multiple signaling pathways associated with innate immune responses, including mitogen-activated protein kinases (MAPKs). In this study, we investigated how systemically-injected AdVs activate two MAPK pathways (p38 and ERK) and the contribution of these kinases to AdV-induced cytokine and chemokine responses in mice. Mice were injected intravenously either with a helper-dependent Ad2 vector that does not express viral genes or transgenes, or with the Ad2 mutant ts1, which is defective in endosomal escape. We found that AdV induced rapid phosphorylation of p38 and ERK as well as a significant cytokine response, but ts1 failed to activate p38 or ERK and induced only a limited cytokine response. These results demonstrate that endosomal escape of virions is a critical step in the induction of these innate pathways and responses. We then examined the roles of p38 and ERK pathways in the innate cytokine response by administering specific kinase inhibitors to mice prior to AdV. The cytokine and chemokine response to AdV was only modestly suppressed by a p38 inhibitor, while an ERK inhibitor has mixed effects, lowering some cytokines and elevating others. Thus, even though p38 and ERK are rapidly activated after i.v. injection of AdV, cytokine and chemokine responses are mostly independent of these kinases. PMID- 22046345 TI - Increase of transmitted drug resistance among HIV-infected sub-Saharan Africans residing in Spain in contrast to the native population. AB - BACKGROUND: The prevalence of transmitted HIV drug resistance (TDR) is stabilizing or decreasing in developed countries. However, this trend is not specifically evaluated among immigrants from regions without well-implemented antiretroviral strategies. METHODS: TDR trends during 1996-2010 were analyzed among naive HIV-infected patients in Spain, considering their origin and other factors. TDR mutations were defined according to the World Health Organization list. RESULTS: Pol sequence was available for 732 HIV-infected patients: 292 native Spanish, 226 sub-Saharan Africans (SSA), 114 Central-South Americans (CSA) and 100 from other regions. Global TDR prevalence was 9.7% (10.6% for Spanish, 8.4% for SSA and 7.9% for CSA). The highest prevalences were found for protease inhibitors (PI) in Spanish (3.1%), for non-nucleoside reverse transcriptase inhibitors (NNRTI) in SSA (6.5%) and for nucleoside reverse transcriptase inhibitors (NRTI) in both Spanish and SSA (6.5%). The global TDR rate decreased from 11.3% in 2004-2006 to 8.4% in 2007-2010. Characteristics related to a decreasing TDR trend in 2007-10 were Spanish and CSA origin, NRTI- and NNRTI resistance, HIV-1 subtype B, male sex and infection through injection drug use. TDR remained stable for PI-resistance, in patients infected through sexual intercourse and in those carrying non-B variants. However, TDR increased among SSA and females. K103N was the predominant mutation in all groups and periods. CONCLUSION: TDR prevalence tended to decrease among HIV-infected native Spanish and Central-South Americans, but it increased up to 13% in sub-Saharan immigrants in 2007-2010. These results highlight the importance of a specific TDR surveillance among immigrants to prevent future therapeutic failures, especially when administering NNRTIs. PMID- 22046346 TI - Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib. AB - BACKGROUND: Overexpression of the ERBB2 kinase is observed in about one-third of breast cancer patients and the dual ERBB1/ERBB2 kinase inhibitor lapatinib was recently approved for the treatment of advanced ERBB2-positive breast cancer. Mutations in the ERBB2 receptor have recently been reported in breast cancer at diagnosis and also in gastric, colorectal and lung cancer. These mutations may have an impact on the clinical responses achieved with lapatinib in breast cancer and may also have a potential impact on the use of lapatinib in other solid cancers. However, the sensitivity of lapatinib towards clinically observed ERBB2 mutations is not known. METHODOLOGY/PRINCIPAL FINDINGS: We cloned a panel of 8 clinically observed ERBB2 mutations, established stable cell lines and characterized their sensitivity towards lapatinib and alternative ERBB2 inhibitors. Both lapatinib-sensitive and lapatinib-resistant ERBB2 mutations were observed. Interestingly, we were able to generate lapatinib resistance mutations in wt-ERBB2 cells incubated with lapatinib for prolonged periods of time. This indicates that these resistance mutations may also cause secondary resistance in lapatinib-treated patients. Lapatinib-resistant ERBB2 mutations were found to be highly resistant towards AEE788 treatment but remained sensitive towards the dual irreversible inhibitors CL-387785 and WZ-4002. CONCLUSIONS/SIGNIFICANCE: Patients harbouring certain ERBB2 kinase domain mutations at diagnosis may not benefit from lapatinib treatment. Moreover, secondary lapatinib resistance may develop due to kinase domain mutations. Irreversible ERBB2 inhibitors may offer alternative treatment options for breast cancer and other solid tumor patients harbouring lapatinib resistance mutations. In addition, these inhibitors may be of interest in the scenario of secondary lapatinib resistance. PMID- 22046347 TI - Differential effects of accumbens core vs. shell lesions in a rat concurrent conditioned place preference paradigm for cocaine vs. social interaction. AB - BACKGROUND: A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. Among these activities, social interaction is doubly important because treatment adherence itself depends on it. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male conspecific (i) reversed CPP from cocaine to social interaction despite continuing cocaine training and (ii) prevented the reinstatement of cocaine CPP. In the present study, we investigated if the two subregions of the nucleus accumbens (Acb), i.e., the core (AcbC) and the shell (AcbSh), would differentially affect CPP for cocaine vs social interaction. METHODOLOGY/PRINCIPAL FINDINGS: Animals were concurrently trained for CPP pairing cocaine with one compartment and social interaction with the other (i.e., mutually exclusive stimulus presentation during training). Excitotoxic lesioning of the AcbC or the BLA shifted CPP toward social interaction, whereas AcbSh inactivation shifted CPP toward cocaine. CONCLUSIONS: Overall, our findings suggest that inactivation of the AcbC or the BLA is sufficient to shift CPP away from a drug of abuse toward social interaction. Lesioning the AcbSh produced the opposite effect. PMID- 22046348 TI - Fishing in the dark: a pursuit-diving seabird modifies foraging behaviour in response to nocturnal light levels. AB - Visual predators tend not to hunt during periods when efficiency is compromised by low light levels. Yet common murres, a species considered a diurnal visual predator, frequently dive at night. To study foraging of murres under different light conditions, we used a combination of archival tagging methods and astronomical models to assess relationships between diving behaviour and light availability. During diurnal and crepuscular periods, murres used a wide range of the water column (2-177 m), foraging across light intensities that spanned several orders of magnitude (10(3)-10(-10) Wm(-2)). Through these periods, they readily dived under conditions equivalent to ambient moonlight (~10(-4) Wm(-2)) but rarely under conditions equivalent to starlight (~10(-8) Wm(-2)). At night, murres readily foraged during both moonlit and starlit periods, and diving depth and efficiency increased with nocturnal light intensity, suggesting that night diving is at least partially visually guided. Whether visually guided foraging is possible during starlit periods is less clear. Given the dense prey landscape available, random-walk simulations suggest that murres could benefit from random prey encounters. We hypothesise that murres foraging through starlit periods rely either on close-range visual or possibly nonvisual cues to acquire randomly encountered prey. This research highlights the flexibility of breeding common murres and raises questions about the strategies and mechanisms birds use to find prey under very low light conditions. PMID- 22046349 TI - Toll-like receptor 3 regulates neural stem cell proliferation by modulating the Sonic Hedgehog pathway. AB - Toll-like receptor 3 (TLR3) signaling has been implicated in neural stem/precursor cell (NPC) proliferation. However, the molecular mechanisms involved, and their relationship to classical TLR-mediated innate immune pathways, remain unknown. Here, we report investigation of the mechanics of TLR3 signaling in neurospheres comprised of epidermal growth factor (EGF)-responsive NPC isolated from murine embryonic cerebral cortex of C57BL/6 (WT) or TLR3 deficient (TLR3(-/-)) mice. Our data indicate that the TLR3 ligand polyinosinic polycytidylic acid (PIC) negatively regulates NPC proliferation by inhibiting Sonic Hedgehog (Shh) signaling, that PIC induces apoptosis in association with inhibition of Ras-ERK signaling and elevated expression of Fas, and that these effects are TLR3-dependent, suggesting convergent signaling between the Shh and TLR3 pathways. PMID- 22046350 TI - Predicting residue-residue contacts and helix-helix interactions in transmembrane proteins using an integrative feature-based random forest approach. AB - Integral membrane proteins constitute 25-30% of genomes and play crucial roles in many biological processes. However, less than 1% of membrane protein structures are in the Protein Data Bank. In this context, it is important to develop reliable computational methods for predicting the structures of membrane proteins. Here, we present the first application of random forest (RF) for residue-residue contact prediction in transmembrane proteins, which we term as TMhhcp. Rigorous cross-validation tests indicate that the built RF models provide a more favorable prediction performance compared with two state-of-the-art methods, i.e., TMHcon and MEMPACK. Using a strict leave-one-protein-out jackknifing procedure, they were capable of reaching the top L/5 prediction accuracies of 49.5% and 48.8% for two different residue contact definitions, respectively. The predicted residue contacts were further employed to predict interacting helical pairs and achieved the Matthew's correlation coefficients of 0.430 and 0.424, according to two different residue contact definitions, respectively. To facilitate the academic community, the TMhhcp server has been made freely accessible at http://protein.cau.edu.cn/tmhhcp. PMID- 22046351 TI - Nebulisation of receptor-targeted nanocomplexes for gene delivery to the airway epithelium. AB - BACKGROUND: Gene therapy mediated by synthetic vectors may provide opportunities for new treatments for cystic fibrosis (CF) via aerosolisation. Vectors for CF must transfect the airway epithelium efficiently and not cause inflammation so they are suitable for repeated dosing. The inhaled aerosol should be deposited in the airways since the cystic fibrosis transmembrane conductance regulator gene (CFTR) is expressed predominantly in the epithelium of the submucosal glands and in the surface airway epithelium. The aim of this project was to develop an optimised aerosol delivery approach applicable to treatment of CF lung disease by gene therapy. METHODOLOGY: The vector suspension investigated in this study comprises receptor-targeting peptides, cationic liposomes and plasmid DNA that self-assemble by electrostatic interactions to form a receptor-targeted nanocomplex (RTN) of approximately 150 nm with a cationic surface charge of +50 mV. The aerodynamic properties of aerosolised nanocomplexes produced with three different nebulisers were compared by determining aerosol deposition in the different stages of a Next Generation Pharmaceutical Impactor (NGI). We also investigated the yield of intact plasmid DNA by agarose gel electrophoresis and densitometry, and transfection efficacies in vitro and in vivo. RESULTS: RTNs nebulised with the AeroEclipse II BAN were the most effective, compared to other nebulisers tested, for gene delivery both in vitro and in vivo. The biophysical properties of the nanocomplexes were unchanged after nebulisation while the deposition of RTNs suggested a range of aerosol aerodynamic sizes between 5.5 um 1.4 um cut off (NGI stages 3-6) compatible with deposition in the central and lower airways. CONCLUSIONS: RTNs showed their ability at delivering genes via nebulisation, thus suggesting their potential applications for therapeutic interventions of cystic fibrosis and other respiratory disorders. PMID- 22046352 TI - Sox9 transcriptionally represses Spp1 to prevent matrix mineralization in maturing heart valves and chondrocytes. AB - Sox9 is an SRY-related transcription factor required for expression of cartilaginous genes in the developing skeletal system and heart valve structures. In contrast to positively regulating cartilaginous matrix, Sox9 also negatively regulates matrix mineralization associated with bone formation. While the transcriptional activation of Sox9 target genes during chondrogenesis has been characterized, the mechanisms by which Sox9 represses osteogenic processes are not so clear. Using ChIP-on-chip and luciferase assays we show that Sox9 binds and represses transactivation of the osteogenic glycoprotein Spp1. In addition, Sox9 knockdown in post natal mouse heart valve explants and rib chondrocyte cultures promotes Spp1 expression and matrix mineralization, while attenuating expression of cartilage genes Type II Collagen and Cartilage Link Protein. Further, we show that Spp1 is required for matrix mineralization induced by Sox9 knockdown. These studies provide insights into the molecular mechanisms by which Sox9 prevents pathologic matrix mineralization in tissues that must remain cartilaginous. PMID- 22046353 TI - Decidual cell polyploidization necessitates mitochondrial activity. AB - Cellular polyploidy has been widely reported in nature, yet its developmental mechanism and function remain poorly understood. In the present study, to better define the aspects of decidual cell polyploidy, we isolated pure polyploid and non-polyploid decidual cell populations from the in vivo decidual bed. Three independent RNA pools prepared for each population were then subjected to the Affymetrix gene chip analysis for the whole mouse genome transcripts. Our data revealed up-regulation of 1015 genes and down-regulation of 1207 genes in the polyploid populations, as compared to the non-polyploid group. Comparative RT-PCR and in situ hybridization results indeed confirmed differential expressional regulation of several genes between the two populations. Based on functional enrichment analyses, up-regulated polyploidy genes appeared to implicate several functions, which primarily include cell/nuclear division, ATP binding, metabolic process, and mitochondrial activity, whereas that of down-regulated genes primarily included apoptosis and immune processes. Further analyses of genes that are related to mitochondria and bi-nucleation showed differential and regional expression within the decidual bed, consistent with the pattern of polyploidy. Consistently, studies revealed a marked induction of mitochondrial mass and ATP production in polyploid cells. The inhibition of mitochondrial activity by various pharmacological inhibitors, as well as by gene-specific targeting using siRNA-mediated technology showed a dramatic attenuation of polyploidy and bi nucleation development during in vitro stromal cell decidualization, suggesting mitochondria play a major role in positive regulation of decidual cell polyploidization. Collectively, analyses of unique polyploidy markers and molecular signaling networks may be useful to further characterize functional aspects of decidual cell polyploidy at the site of implantation. PMID- 22046354 TI - Intracellular kinases mediate increased translation and secretion of netrin-1 from renal tubular epithelial cells. AB - BACKGROUND: Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS) to determine the signaling pathways that regulate netrin-1 production in response to injury. METHODS AND PRINCIPAL FINDINGS: Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability. CONCLUSION: Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells. PMID- 22046355 TI - Anti-GBM glomerulonephritis involves IL-1 but is independent of NLRP3/ASC inflammasome-mediated activation of caspase-1. AB - IL-1beta and IL-18 are proinflammatory cytokines that contribute to renal immune complex disease, but whether IL-1beta and IL-18 are mediators of intrinsic glomerular inflammation is unknown. In contrast to other cytokines the secretion of IL-1beta and IL-18 requires a second stimulus that activates the inflammasome ASC-caspase-1 pathway to cleave pro-IL-1beta and -IL-18 into their mature and secretable forms. As the NLRP3 inflammasome and caspase-1 were shown to contribute to postischemic and postobstructive tubulointerstitial inflammation, we hypothesized a similar role for NLRP3, ASC, and caspase-1 in glomerular immunopathology. This concept was supported by the finding that lack of IL-1R1 reduced antiserum-induced focal segmental necrosis, crescent formation, and tubular atrophy when compared to wildtype mice. Lack of IL-18 reduced tubular atrophy only. However, NLRP3-, ASC- or caspase-1-deficiency had no significant effect on renal histopathology or proteinuria of serum nephritis. In vitro studies with mouse glomeruli or mesangial cells, glomerular endothelial cells, and podocytes did not reveal any pro-IL-1beta induction upon LPS stimulation and no caspase-1 activation after an additional exposure to the NLRP3 agonist ATP. Only renal dendritic cells, which reside mainly in the tubulointerstitium, expressed pro-IL-1beta and were able to activate the NLRP3-caspase-1 axis and secrete mature IL-1beta. Together, the NLRP3-ASC-caspase-1 axis does not contribute to intrinsic glomerular inflammation via glomerular parenchymal cells as these cannot produce IL-1beta during sterile inflammation. PMID- 22046356 TI - Individual analyses of Levy walk in semi-free ranging Tonkean macaques (Macaca tonkeana). AB - Animals adapt their movement patterns to their environment in order to maximize their efficiency when searching for food. The Levy walk and the Brownian walk are two types of random movement found in different species. Studies have shown that these random movements can switch from a Brownian to a Levy walk according to the size distribution of food patches. However no study to date has analysed how characteristics such as sex, age, dominance or body mass affect the movement patterns of an individual. In this study we used the maximum likelihood method to examine the nature of the distribution of step lengths and waiting times and assessed how these distributions are influenced by the age and the sex of group members in a semi free-ranging group of ten Tonkean macaques. Individuals highly differed in their activity budget and in their movement patterns. We found an effect of age and sex of individuals on the power distribution of their step lengths and of their waiting times. The males and old individuals displayed a higher proportion of longer trajectories than females and young ones. As regards waiting times, females and old individuals displayed higher rates of long stationary periods than males and young individuals. These movement patterns resembling random walks can probably be explained by the animals moving from one location to other known locations. The power distribution of step lengths might be due to a power distribution of food patches in the enclosure while the power distribution of waiting times might be due to the power distribution of the patch sizes. PMID- 22046357 TI - N-cofilin can compensate for the loss of ADF in excitatory synapses. AB - Actin plays important roles in a number of synaptic processes, including synaptic vesicle organization and exocytosis, mobility of postsynaptic receptors, and synaptic plasticity. However, little is known about the mechanisms that control actin at synapses. Actin dynamics crucially depend on LIM kinase 1 (LIMK1) that controls the activity of the actin depolymerizing proteins of the ADF/cofilin family. While analyses of mouse mutants revealed the importance of LIMK1 for both pre- and postsynaptic mechanisms, the ADF/cofilin family member n-cofilin appears to be relevant merely for postsynaptic plasticity, and not for presynaptic physiology. By means of immunogold electron microscopy and immunocytochemistry, we here demonstrate the presence of ADF (actin depolymerizing factor), a close homolog of n-cofilin, in excitatory synapses, where it is particularly enriched in presynaptic terminals. Surprisingly, genetic ablation of ADF in mice had no adverse effects on synapse structure or density as assessed by electron microscopy and by the morphological analysis of Golgi-stained hippocampal pyramidal cells. Moreover, a series of electrophysiological recordings in acute hippocampal slices revealed that presynaptic recruitment and exocytosis of synaptic vesicles as well as postsynaptic plasticity were unchanged in ADF mutant mice. The lack of synaptic defects may be explained by the elevated n-cofilin levels observed in synaptic structures of ADF mutants. Indeed, synaptic actin regulation was impaired in compound mutants lacking both ADF and n-cofilin, but not in ADF single mutants. From our results we conclude that n-cofilin can compensate for the loss of ADF in excitatory synapses. Further, our data suggest that ADF and n-cofilin cooperate in controlling synaptic actin content. PMID- 22046358 TI - Epigenetic changes with dietary soy in cynomolgus monkeys. AB - Nutritional interventions are important alternatives for reducing the prevalence of many chronic diseases. Soy is a good source of protein that contains isoflavones, including genistein and daidzein, and may alter the risk of obesity, Type 2 diabetes, osteoporosis, cardiovascular disease, and reproductive cancers. We have shown previously in nonhuman primates that soy protein containing isoflavones leads to improved body weight, insulin sensitivity, lipid profiles, and atherosclerosis compared to protein without soy isoflavones (casein), and does not increase the risk of cancer. Since genistein has been shown to alter DNA methylation, we compared the methylation profiles of cynomolgus monkeys, from multiple tissues, eating two high-fat, typical American diets (TAD) with similar macronutrient contents, with or without soy protein. DNA methylation status was successfully determined for 80.6% of the probes in at least one tissue using Illumina's HumanMethylation27 BeadChip. Overall methylation increased in liver and muscle tissue when monkeys switched from the TAD-soy to the TAD-casein diets. Genes involved in epigenetic processes, specifically homeobox genes (HOXA5, HOXA11, and HOXB1), and ABCG5 were among those that changed between diets. These data support the use of the HumanMethylation27 BeadChip in cynomolgus monkeys and identify epigenetic changes associated with dietary interventions with soy protein that may potentially affect the etiology of complex diseases. PMID- 22046359 TI - Novel adiponectin variants identified in type 2 diabetic patients reveal multimerization and secretion defects. AB - ADIPOQ, encoding adiponectin, is a candidate gene for type 2 diabetes (T2D) identified by genome-wide linkage analyses with supporting evidence showing the protein function in sensitizing insulin actions. In an endeavor to characterize candidate genes causing T2D in Thai patients, we identified 10 novel ADIPOQ variations, several of which were non-synonymous variations observed only in the patients. To examine the impact of these non-synonymous variations on adiponectin structure and biochemical characteristics, we conducted a structural analysis of the wild-type and variant proteins by in silico modeling and further characterized biochemical properties of the variants with predicted structural abnormalities from the modeling by molecular and biochemical studies. The recombinant plasmids containing wild-type and variant ADIPOQ cDNAs derived from the variations identified by our study (R55H, R112H, and R131H) and previous work (G90S and R112C) were constructed and transiently expressed and co-expressed in cultured HEK293T cells to investigate their oligomerization, interaction, and secretion. We found that the novel R55H variant impaired protein multimerization but it did not exert the effect over the co-expressed wild-type protein while novel R131H variant impaired protein secretion and also affected the co-expressed wild-type protein in a dominant negative fashion. The R131H variant could traffic from the endoplasmic reticulum to the Golgi, trans-Golgi network, and early endosome but could not be secreted. The R131H variant was likely to be degraded through the lysosomal system and inhibition of its degradation rescued the variant protein from secretion defect. We have shown the possibility of using in silico modeling for predicting the effect of amino acid substitution on adiponectin oligomerization. This is also the first report that demonstrates a dominant negative effect of the R131H variant on protein secretion and the possibility of using protein degradation inhibitors as therapeutic agents in the patients carrying adiponectin variants with secretion defect. PMID- 22046360 TI - Host centrality in food web networks determines parasite diversity. AB - BACKGROUND: Parasites significantly alter topological metrics describing food web structure, yet few studies have explored the relationship between food web topology and parasite diversity. METHODS/PRINCIPAL FINDINGS: This study uses quantitative metrics describing network structure to investigate the relationship between the topology of the host food web and parasite diversity. Food webs were constructed for four restored brackish marshes that vary in species diversity, time post restoration and levels of parasitism. Our results show that the topology of the food web in each brackish marsh is highly nested, with clusters of generalists forming a distinct modular structure. The most consistent predictors of parasite diversity within a host were: trophic generality, and eigenvector centrality. These metrics indicate that parasites preferentially colonise host species that are highly connected, and within modules of tightly interacting species in the food web network. CONCLUSIONS/SIGNIFICANCE: These results suggest that highly connected free-living species within the food web may represent stable trophic relationships that allow for the persistence of complex parasite life cycles. Our data demonstrate that the structure of host food webs can have a significant effect on the establishment of parasites, and on the potential for evolution of complex parasite life cycles. PMID- 22046361 TI - Evidence for retrogene origins of the prion gene family. AB - The evolutionary origin of prion genes, only known to exist in the vertebrate lineage, had remained elusive until recently. Following a lead from interactome investigations of the murine prion protein, our previous bioinformatic analyses revealed the evolutionary descent of prion genes from an ancestral ZIP metal ion transporter. However, the molecular mechanism of evolution remained unexplored. Here we present a computational investigation of this question based on sequence, intron-exon, synteny and pseudogene analyses. Our data suggest that during the emergence of metazoa, a cysteine-flanked core domain was modularly inserted, or arose de novo, in a preexisting ZIP ancestor gene to generate a prion-like ectodomain in a subbranch of ZIP genes. Approximately a half-billion years later, a genomic insertion of a spliced transcript coding for such a prion-like ZIP ectodomain may have created the prion founder gene. We document that similar genomic insertions involving ZIP transcripts, and probably relying on retropositional elements, have indeed occurred more than once throughout evolution. PMID- 22046362 TI - The transcriptome of the reference potato genome Solanum tuberosum Group Phureja clone DM1-3 516R44. AB - Advances in molecular breeding in potato have been limited by its complex biological system, which includes vegetative propagation, autotetraploidy, and extreme heterozygosity. The availability of the potato genome and accompanying gene complement with corresponding gene structure, location, and functional annotation are powerful resources for understanding this complex plant and advancing molecular breeding efforts. Here, we report a reference for the potato transcriptome using 32 tissues and growth conditions from the doubled monoploid Solanum tuberosum Group Phureja clone DM1-3 516R44 for which a genome sequence is available. Analysis of greater than 550 million RNA-Seq reads permitted the detection and quantification of expression levels of over 22,000 genes. Hierarchical clustering and principal component analyses captured the biological variability that accounts for gene expression differences among tissues suggesting tissue-specific gene expression, and genes with tissue or condition restricted expression. Using gene co-expression network analysis, we identified 18 gene modules that represent tissue-specific transcriptional networks of major potato organs and developmental stages. This information provides a powerful resource for potato research as well as studies on other members of the Solanaceae family. PMID- 22046363 TI - Responses of peripheral blood flow to acute hypoxia and hyperoxia as measured by optical microangiography. AB - Oxygen availability is regarded as a critical factor to metabolically regulate systemic blood flow. There is a debate as to how peripheral blood flow (PBF) is affected and modulated during hypoxia and hyperoxia; however in vivo evaluating of functional PBF under oxygen-related physiological perturbation remains challenging. Microscopic observation, the current frequently used imaging modality for PBF characterization often involves the use of exogenous contrast agents, which would inevitably perturb the intrinsic physiologic responses of microcirculation being investigated. In this paper, optical micro-angiography (OMAG) was employed that uses intrinsic optical scattering signals backscattered from blood flows for imaging PBF in skeletal muscle challenged by the alteration of oxygen concentration. By utilizing optical reflectance signals, we demonstrated that OMAG is able to show the response of hemodynamic activities upon acute hypoxia and hyperoxia, including the modulation of macrovascular caliber, microvascular density, and flux regulation within different sized vessels within skeletal muscle in mice in vivo. Our results suggest that OMAG is a promising tool for in vivo monitoring of functional macro- or micro-vascular responses within peripheral vascular beds. PMID- 22046364 TI - The fission yeast RNA binding protein Mmi1 regulates meiotic genes by controlling intron specific splicing and polyadenylation coupled RNA turnover. AB - The polyA tails of mRNAs are monitored by the exosome as a quality control mechanism. We find that fission yeast, Schizosaccharomyces pombe, adopts this RNA quality control mechanism to regulate a group of 30 or more meiotic genes at the level of both splicing and RNA turnover. In vegetative cells the RNA binding protein Mmi1 binds to the primary transcripts of these genes. We find the novel motif U(U/C/G)AAAC highly over-represented in targets of Mmi1. Mmi1 can specifically regulate the splicing of particular introns in a transcript: it inhibits the splicing of introns that are in the vicinity of putative Mmi1 binding sites, while allowing the splicing of other introns that are far from such sites. In addition, binding of Mmi1, particularly near the 3' end, alters 3' processing to promote extremely long polyA tails of up to a kilobase. The hyperadenylated transcripts are then targeted for degradation by the nuclear exonuclease Rrp6. The nuclear polyA binding protein Pab2 assists this hyperadenylation-mediated RNA decay. Rrp6 also targets other hyperadenylated transcripts, which become hyperadenylated in an unknown, but Mmi1-independent way. Thus, hyperadenylation may be a general signal for RNA degradation. In addition, binding of Mmi1 can affect the efficiency of 3' cleavage. Inactivation of Mmi1 in meiosis allows meiotic expression, through splicing and RNA stabilization, of at least 29 target genes, which are apparently constitutively transcribed. PMID- 22046365 TI - Mechanism of acetylcholine receptor cluster formation induced by DC electric field. AB - BACKGROUND: The formation of acetylcholine receptor (AChR) cluster is a key event during the development of the neuromuscular junction. It is induced through the activation of muscle-specific kinase (MuSK) by the heparan-sulfate proteoglycan agrin released from the motor axon. On the other hand, DC electric field, a non neuronal stimulus, is also highly effective in causing AChRs to cluster along the cathode-facing edge of muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: To understand its molecular mechanism, quantum dots (QDs) were used to follow the movement of AChRs as they became clustered under the influence of electric field. From analyses of trajectories of AChR movement in the membrane, it was concluded that diffuse receptors underwent Brownian motion until they were immobilized at sites of cluster formation. This supports the diffusion-mediated trapping model in explaining AChR clustering under the influence of this stimulus. Disrupting F actin cytoskeleton assembly and interfering with rapsyn-AChR interaction suppressed this phenomenon, suggesting that these are integral components of the trapping mechanism induced by the electric field. Consistent with the idea that signaling pathways are activated by this stimulus, the localization of tyrosine phosphorylated forms of AChR beta-subunit and Src was observed at cathodal AChR clusters. Furthermore, disrupting MuSK activity through the expression of a kinase-dead form of this enzyme abolished electric field-induced AChR clustering. CONCLUSIONS: These results suggest that DC electric field as a physical stimulus elicits molecular reactions in muscle cells in the form of cathodal MuSK activation in a ligand-free manner to trigger a signaling pathway that leads to cytoskeletal assembly and AChR clustering. PMID- 22046366 TI - Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice. AB - Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging. PMID- 22046367 TI - Stigmatising attitudes among people offered home-based HIV testing and counselling in Blantyre, Malawi: construction and analysis of a stigma scale. AB - BACKGROUND: HIV/AIDS related stigma is a major barrier to uptake of HIV testing and counselling (HTC). We assessed the extent of stigmatising attitudes expressed by participants offered community-based HTC, and their anticipated stigma from others to assess relationship with HIV test uptake. From these data, we constructed a brief stigma scale for use around the time of HIV testing. METHODS AND FINDINGS: Adult members of 60 households in urban Blantyre, Malawi, were selected using population-weighted random cluster sampling and offered HTC with the option to self-test before confirmatory HTC. Prior to HTC a 15-item HIV stigma questionnaire was administered. We used association testing and principal components analysis (PCA) to construct a scale measure of stigma. Of 226 adults invited to participate, 216 (95.6%) completed questionnaires and 198/216 (91.7%) opted to undergo HTC (all self-tested). Stigmatising attitudes were uncommon, but anticipated stigma was common, especially fearing verbal abuse (22%) or being abandoned by their partner (11%). Three questions showed little association or consistency with the remaining 12 stigma questions and were not included in the final scale. For the 12-question final scale, Cronbach's alpha was 0.75. Level of stigma was not associated with previously having tested for HIV (p = 0.318) or agreeing to HTC (p = 0.379), but was associated with expressed worry about being or becoming HIV infected (p = 0.003). CONCLUSIONS: Anticipated stigma prior to HTC was common among both men and women. However, the high uptake of HTC suggests that this did not translate into reluctance to accept community-based testing. We constructed a brief scale to measure stigma at the time of HIV testing that could rapidly identify individuals requiring additional support following diagnosis and monitor the impact of increasing availability of community-based HTC on prevalence of stigma. PMID- 22046368 TI - EP receptor expression in human intestinal epithelium and localization relative to the stem cell zone of the crypts. AB - There is substantial evidence for PGE2 affecting intestinal epithelial proliferation. PGE2 is also reported to be involved in the regulation of growth and differentiation in adult stem cells, both effects mediated by binding to EP receptors. We have used the Lgr5 as a marker to scrutinize EP-receptor and COX expression in human intestinal epithelial cells with focus on the stem cell area of the crypts. Normal tissue from ileum and colon, but also duodenal biopsies from patients with untreated celiac disease, were investigated by immunohistochemistry and RT-PCR. The combination of fresh flash-frozen tissue and laser microdissection made it possible to isolate RNA from the epithelial cell layer, only. In the small intestine, Lgr5 labels cells are in the +4 position, while in the colon, Lgr5 positive cells are localized to the crypt bottoms. Epithelial crypt cells of normal small intestine expressed neither EP-receptor mRNA nor COX1/2. However, crypt cells in tissue from patients with untreated celiac disease expressed EP2/4 receptor and COX1 mRNA. In the colon, the situation was different. Epithelial crypt cells from normal colon were found to express EP2/4 receptor and COX1/2 transcripts. Thus, there are distinct differences between normal human small intestine and colon with regard to expression of EP2/4 receptors and COX1/2. In normal colon tissue, PGE2-mediated signaling through EP-receptors 2/4 could be involved in regulation of growth and differentiation of the epithelium, while the lack of EP-receptor expression in the small intestinal tissue exclude the possibility of a direct effect of PGE2 on the crypt epithelial cells. PMID- 22046369 TI - Species-specific codon context rules unveil non-neutrality effects of synonymous mutations. AB - BACKGROUND: Codon pair usage (codon context) is a species specific gene primary structure feature whose evolutionary and functional roles are poorly understood. The data available show that codon-context has direct impact on both translation accuracy and efficiency, but one does not yet understand how it affects these two translation variables or whether context biases shape gene evolution. METHODOLOGIES/PRINCIPAL FINDINGS: Here we study codon-context biases using a set of 72 orthologous highly conserved genes from bacteria, archaea, fungi and high eukaryotes to identify 7 distinct groups of codon context rules. We show that synonymous mutations, i.e., neutral mutations that occur in synonymous codons of codon-pairs, are selected to maintain context biases and that non-synonymous mutations, i.e., non-neutral mutations that alter protein amino acid sequences, are also under selective pressure to preserve codon-context biases. CONCLUSIONS: Since in vivo studies provide evidence for a role of codon context on decoding fidelity in E. coli and for decoding efficiency in mammalian cells, our data support the hypothesis that, like codon usage, codon context modulates the evolution of gene primary structure and fine tunes the structure of open reading frames for high genome translational fidelity and efficiency in the 3 domains of life. PMID- 22046370 TI - Evidence of infection with H4 and H11 avian influenza viruses among Lebanese chicken growers. AB - Human infections with H5, H7, and H9 avian influenza viruses are well documented. Exposure to poultry is the most important risk factor for humans becoming infected with these viruses. Data on human infection with other low pathogenicity avian influenza viruses is sparse but suggests that such infections may occur. Lebanon is a Mediterranean country lying under two major migratory birds flyways and is home to many wild and domestic bird species. Previous reports from this country demonstrated that low pathogenicity avian influenza viruses are in circulation but highly pathogenic H5N1 viruses were not reported. In order to study the extent of human infection with avian influenza viruses in Lebanon, we carried out a seroprevalence cross-sectional study into which 200 poultry-exposed individuals and 50 non-exposed controls were enrolled. We obtained their sera and tested it for the presence of antibodies against avian influenza viruses types H4 through H16 and used a questionnaire to collect exposure data. Our microneutralization assay results suggested that backyard poultry growers may have been previously infected with H4 and H11 avian influenza viruses. We confirmed these results by using a horse red blood cells hemagglutination inhibition assay. Our data also showed that farmers with antibodies against each virus type clustered in a small geographic area suggesting that unrecognized outbreaks among birds may have led to these human infections. In conclusion, this study suggests that occupational exposure to chicken is a risk factor for infection with avian influenza especially among backyard growers and that H4 and H11 influenza viruses may possess the ability to cross the species barrier to infect humans. PMID- 22046371 TI - Neural cell 3D microtissue formation is marked by cytokines' up-regulation. AB - Cells cultured in three dimensional (3D) scaffolds as opposed to traditional two dimensional (2D) substrates have been considered more physiologically relevant based on their superior ability to emulate the in vivo environment. Combined with stem cell technology, 3D cell cultures can provide a promising alternative for use in cell-based assays or biosensors in non-clinical drug discovery studies. To advance 3D culture technology, a case has been made for identifying and validating three-dimensionality biomarkers. With this goal in mind, we conducted a transcriptomic expression comparison among neural progenitor cells cultured on 2D substrates, 3D porous polystyrene scaffolds, and as 3D neurospheres (in vivo surrogate). Up-regulation of cytokines as a group in 3D and neurospheres was observed. A group of 13 cytokines were commonly up-regulated in cells cultured in polystyrene scaffolds and neurospheres, suggesting potential for any or a combination from this list to serve as three-dimensionality biomarkers. These results are supportive of further cytokine identification and validation studies with cells from non-neural tissue. PMID- 22046372 TI - Increasing antiproliferative properties of endocannabinoids in N1E-115 neuroblastoma cells through inhibition of their metabolism. AB - The antitumoral properties of endocannabinoids received a particular attention these last few years. Indeed, these endogenous molecules have been reported to exert cytostatic, apoptotic and antiangiogenic effects in different tumor cell lines and tumor xenografts. Therefore, we investigated the cytotoxicity of three N-acylethanolamines--N-arachidonoylethanolamine (anandamide, AEA), N palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA)--which were all able to time- and dose-dependently reduce the viability of murine N1E-115 neuroblastoma cells. Moreover, several inhibitors of FAAH and NAAA, whose presence was confirmed by RT-PCR in the cell line, induced cell cytotoxicity and favored the decrease in cell viability caused by N-acylethanolamines. The most cytotoxic treatment was achieved by the co-incubation of AEA with the selective FAAH inhibitor URB597, which drastically reduced cell viability partly by inhibiting AEA hydrolysis and consequently increasing AEA levels. This combination of molecules synergistically decreased cell proliferation without inducing cell apoptosis or necrosis. We found that these effects are independent of cannabinoid, TRPV1, PPARalpha, PPARgamma or GPR55 receptors activation but seem to occur through a lipid raft-dependent mechanism. These findings further highlight the interest of targeting the endocannabinoid system to treat cancer. More particularly, this emphasizes the great potential benefit of designing novel anti-cancerous therapies based on the association of endocannabinoids and inhibitors of their hydrolysis. PMID- 22046373 TI - A Brassica napus lipase locates at the membrane contact sites involved in chloroplast development. AB - BACKGROUND: Fatty acids synthesized in chloroplast are transported to endoplasmic reticulum (ER) for triacylglycerols (TAGs) resembling. The development of chloroplast also requires lipids trafficking from ER to chloroplast. The membrane contact sites (MCSs) between ER and chloroplast has been demonstrated to be involved for the trafficking of lipids and proteins. Lipids trafficking between ER and chloroplast is often accompanied by lipids interconversion. However, it is rarely known how lipids interconversion happens during their trafficking. METHODOLOGY/PRINCIPAL FINDINGS: We cloned a lipase gene from Brassica napus L., designated as BnCLIP1. Green fluorescence protein (GFP)-tagged BnCLIP1 was shown to locate at the MCSs between ER and chloroplasts in tobacco leaves. Heterogeneous expression of BnCLIP1 in Saccharomyces cerevisiae (pep4) reduced the total amount of fatty acid. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the truncated BnCLIP1 had a substrate preference for C16:0 lipids in Saccharomyces cerevisiae (pep4). To probe the physiological function of BnCLIP1, two Brassica napus lines with different oil-content were introduced to investigate the transcript patterns of BnCLIP1 during seed development. Intriguingly, the transcript level of BnCLIP1 was found to be immediately up regulated during the natural seed senescence of both lines; the transcription response of BnCLIP1 in the high oil-content seeds was faster than the lower ones, suggesting a potential role of BnCLIP1 in affecting seed oil synthesis via regulating chloroplast integrity. Further researches showed that chemical disruption of leaf chloroplast also activated the transcription of BnCLIP1. CONCLUSIONS/SIGNIFICANCE: The findings of this study show that BnCLIP1 encodes a lipase, localizes at the MCSs and involves in chloroplast development. PMID- 22046374 TI - Transcriptional and functional analysis of the effects of magnolol: inhibition of autolysis and biofilms in Staphylococcus aureus. AB - BACKGROUND: The targeting of Staphylococcus aureus biofilm structures are now gaining interest as an alternative strategy for developing new types of antimicrobial agents. Magnolol (MOL) shows inhibitory activity against S. aureus biofilms and Triton X-100-induced autolysis in vitro, although there are no data regarding the molecular mechanisms of MOL action in bacteria. METHODOLOGY/PRINCIPAL FINDINGS: The molecular basis of the markedly reduced autolytic phenotype and biofilm inhibition triggered by MOL were explored using transcriptomic analysis, and the transcription of important genes were verified by real-time RT-PCR. The inhibition of autolysis by MOL was evaluated using quantitative bacteriolytic assays and zymographic analysis, and antibiofilm activity assays and confocal laser scanning microscopy were used to elucidate the inhibition of biofilm formation caused by MOL in 20 clinical isolates or standard strains. The reduction in cidA, atl, sle1, and lytN transcript levels following MOL treatment was consistent with the induced expression of their autolytic repressors lrgA, lrgB, arlR, and sarA. MOL generally inhibited or reversed the expression of most of the genes involved in biofilm production. The growth of S. aureus strain ATCC 25923 in the presence of MOL dose-dependently led to decreases in Triton X-100-induced autolysis, extracellular murein hydrolase activity, and the amount of extracellular DNA (eDNA). MOL may impede biofilm formation by reducing the expression of cidA, a murein hydrolase regulator, to inhibit autolysis and eDNA release, or MOL may directly repress biofilm formation. CONCLUSIONS/SIGNIFICANCE: MOL shows in vitro antimicrobial activity against clinical and standard S. aureus strains grown in planktonic and biofilm cultures, suggesting that the structure of MOL may potentially be used as a basis for the development of drugs targeting biofilms. PMID- 22046375 TI - Carrageenans, sulphated polysaccharides of red seaweeds, differentially affect Arabidopsis thaliana resistance to Trichoplusia ni (cabbage looper). AB - Carrageenans are a collective family of linear, sulphated galactans found in a number of commercially important species of marine red alga. These polysaccharides are known to elicit defense responses in plant and animals and possess anti-viral properties. We investigated the effect of foliar application of iota-, kappa- and lambda-carrageenans (representing various levels of sulphation) on Arabidopsis thaliana in resistance to the generalist insect Trichoplusia ni (cabbage looper) which is known to cause serious economic losses in crop plants. Plants treated with iota- and kappa-carrageenan showed reduced leaf damage, whereas those treated with lambda- carrageenan were similar to that of the control. In a no-choice test, larval weight was reduced by more than 20% in iota- and kappa- carrageenan treatments, but unaffected by lambda-carrageenan. In multiple choice tests, carrageenan treated plants attracted fewer T. ni larvae by the fourth day following infestation as compared to the control. The application of carrageenans did not affect oviposition behaviour of T. ni. Growth of T. ni feeding on an artificial diet amended with carrageenans was not different from that fed with untreated control diet. iota-carrageenan induced the expression of defense genes; PR1, PDF1.2, and TI1, but kappa- and lambda carrageenans did not. Besides PR1, PDF1.2, and TI1, the indole glucosinolate biosynthesis genes CYP79B2, CYP83B1 and glucosinolate hydrolysing QTL, ESM1 were up-regulated by iota-carrageenan treatment at 48 h post infestation. Gas chromatography-mass spectrometry analysis of carrageenan treated leaves showed increased concentrations of both isothiocyanates and nitriles. Taken together, these results show that carrageenans have differential effects on Arabidopsis resistance to T. ni and that the degree of sulphation of the polysaccharide chain may well mediate this effect. PMID- 22046376 TI - Effects of elevated CO2 and N addition on growth and N2 fixation of a legume subshrub (Caragana microphylla Lam.) in temperate grassland in China. AB - It is well demonstrated that the responses of plants to elevated atmospheric CO(2) concentration are species-specific and dependent on environmental conditions. We investigated the responses of a subshrub legume species, Caragana microphylla Lam., to elevated CO(2) and nitrogen (N) addition using open-top chambers in a semiarid temperate grassland in northern China for three years. Measured variables include leaf photosynthetic rate, shoot biomass, root biomass, symbiotic nitrogenase activity, and leaf N content. Symbiotic nitrogenase activity was determined by the C(2)H(2) reduction method. Elevated CO(2) enhanced photosynthesis and shoot biomass by 83% and 25%, respectively, and the enhancement of shoot biomass was significant only at a high N concentration. In addition, the photosynthetic capacity of C. microphylla did not show down regulation under elevated CO(2). Elevated CO(2) had no significant effect on root biomass, symbiotic nitrogenase activity and leaf N content. Under elevated CO(2), N addition stimulated photosynthesis and shoot biomass. By contrast, N addition strongly inhibited symbiotic nitrogenase activity and slightly increased leaf N content of C. microphylla under both CO(2) levels, and had no significant effect on root biomass. The effect of elevated CO(2) and N addition on C. microphylla did not show interannual variation, except for the effect of N addition on leaf N content. These results indicate that shoot growth of C. microphylla is more sensitive to elevated CO(2) than is root growth. The stimulation of shoot growth of C. microphylla under elevated CO(2) or N addition is not associated with changes in N(2)-fixation. Additionally, elevated CO(2) and N addition interacted to affect shoot growth of C. microphylla with a stimulatory effect occurring only under combination of these two factors. PMID- 22046377 TI - Crystal structure of outer membrane protein NMB0315 from Neisseria meningitidis. AB - NMB0315 is an outer membrane protein of Neisseria meningitidis serogroup B (NMB) and a potential candidate for a broad-spectrum vaccine against meningococcal disease. The crystal structure of NMB0315 was solved by single-wavelength anomalous dispersion (SAD) at a resolution of 2.4 A and revealed to be a lysostaphin-type peptidase of the M23 metallopeptidase family. The overall structure consists of three well-separated domains and has no similarity to any previously published structure. However, only the topology of the carboxyl terminal domain is highly conserved among members of this family, and this domain is a zinc-dependent catalytic unit. The amino-terminal domain of the structure blocks the substrate binding pocket in the carboxyl-terminal domain, indicating that the wild-type full-length protein is in an inactive conformational state. Our studies improve the understanding of the catalytic mechanism of M23 metallopeptidases. PMID- 22046378 TI - How did the spider cross the river? Behavioral adaptations for river-bridging webs in Caerostris darwini (Araneae: Araneidae). AB - BACKGROUND: Interspecific coevolution is well described, but we know significantly less about how multiple traits coevolve within a species, particularly between behavioral traits and biomechanical properties of animals' "extended phenotypes". In orb weaving spiders, coevolution of spider behavior with ecological and physical traits of their webs is expected. Darwin's bark spider (Caerostris darwini) bridges large water bodies, building the largest known orb webs utilizing the toughest known silk. Here, we examine C. darwini web building behaviors to establish how bridge lines are formed over water. We also test the prediction that this spider's unique web ecology and architecture coevolved with new web building behaviors. METHODOLOGY: We observed C. darwini in its natural habitat and filmed web building. We observed 90 web building events, and compared web building behaviors to other species of orb web spiders. CONCLUSIONS: Caerostris darwini uses a unique set of behaviors, some unknown in other spiders, to construct its enormous webs. First, the spiders release unusually large amounts of bridging silk into the air, which is then carried downwind, across the water body, establishing bridge lines. Second, the spiders perform almost no web site exploration. Third, they construct the orb capture area below the initial bridge line. In contrast to all known orb-weavers, the web hub is therefore not part of the initial bridge line but is instead built de novo. Fourth, the orb contains two types of radial threads, with those in the upper half of the web doubled. These unique behaviors result in a giant, yet rather simplified web. Our results continue to build evidence for the coevolution of behavioral (web building), ecological (web microhabitat) and biomaterial (silk biomechanics) traits that combined allow C. darwini to occupy a unique niche among spiders. PMID- 22046379 TI - Systems analysis of ATF3 in stress response and cancer reveals opposing effects on pro-apoptotic genes in p53 pathway. AB - Stress-inducible transcription factors play a pivotal role in cellular adaptation to environment to maintain homeostasis and integrity of the genome. Activating transcription factor 3 (ATF3) is induced by a variety of stress and inflammatory conditions and is over-expressed in many kinds of cancer cells. However, molecular mechanisms underlying pleiotropic functions of ATF3 have remained elusive. Here we employed systems analysis to identify genome-wide targets of ATF3 that is either induced by an alkylating agent methyl methanesulfonate (MMS) or over-expressed in a prostate tumour cell line LNCaP. We show that stress induced and cancer-associated ATF3 is recruited to 5,984 and 1,423 targets, respectively, in the human genome, 89% of which are common. Notably, ATF3 targets are highly enriched for not only ATF/CRE motifs but also binding sites of several other stress-inducible transcription factors indicating an extensive network of stress response factors in transcriptional regulation of target genes. Further analysis of effects of ATF3 knockdown on these targets revealed that stress induced ATF3 regulates genes in metabolic pathways, cell cycle, apoptosis, cell adhesion, and signalling including insulin, p53, Wnt, and VEGF pathways. Cancer associated ATF3 is involved in regulation of distinct sets of genes in processes such as calcium signalling, Wnt, p53 and diabetes pathways. Notably, stress induced ATF3 binds to 40% of p53 targets and activates pro-apoptotic genes such as TNFRSF10B/DR5 and BBC3/PUMA. Cancer-associated ATF3, by contrast, represses these pro-apoptotic genes in addition to CDKN1A/p21. Taken together, our data reveal an extensive network of stress-inducible transcription factors and demonstrate that ATF3 has opposing, cell context-dependent effects on p53 target genes in DNA damage response and cancer development. PMID- 22046380 TI - Changes in waist circumference and the incidence of acute myocardial infarction in middle-aged men and women. AB - BACKGROUND: Waist circumference (WC) measured at one point in time is positively associated with the risk of acute myocardial infarction (MI), but the association with changes in WC (DWC) is not clear. We investigated the association between DWC and the risk of MI in middle-aged men and women, and evaluated the influence from concurrent changes in BMI (DBMI). METHODOLOGY/PRINCIPAL FINDINGS: Data on 38,593 participants from the Danish Diet, Cancer and Health study was analysed. Anthropometry was assessed in 1993-97 and 1999-02. Information on fatal and non fatal MI was obtained from National Registers. Cases were validated by review of the medical records. Hazard ratios (HR) were calculated from Cox proportional hazard models with individuals considered at risk from 1999-02 until December 30 2009. During 8.4 years of follow-up, 1,041 incident cases of MI occurred. WC was positively associated with the risk of MI, but weakly after adjustment for BMI. DWC was not associated with the risk of MI (HR per 5 cm change = 1.01 (0.95, 1.09) with adjustment for covariates, baseline WC, BMI and DBMI). Associations with DWC were not notably different in sub-groups stratified according to baseline WC or DBMI, or when individuals with MI occurring within the first years of follow-up were excluded. CONCLUSIONS/SIGNIFICANCE: WC was positively associated with the risk of MI in middle-aged men and women, but changes in WC were not. These findings suggest that a reduction in WC may be an insufficient target for prevention of MI in middle-aged men and women. PMID- 22046381 TI - Molecular evidence of the toxic effects of diatom diets on gene expression patterns in copepods. AB - BACKGROUND: Diatoms are dominant photosynthetic organisms in the world's oceans and are considered essential in the transfer of energy through marine food chains. However, these unicellular plants at times produce secondary metabolites such as polyunsaturated aldehydes and other products deriving from the oxidation of fatty acids that are collectively termed oxylipins. These cytotoxic compounds are responsible for growth inhibition and teratogenic activity, potentially sabotaging future generations of grazers by inducing poor recruitment in marine organisms such as crustacean copepods. PRINCIPAL FINDINGS: Here we show that two days of feeding on a strong oxylipin-producing diatom (Skeletonema marinoi) is sufficient to inhibit a series of genes involved in aldehyde detoxification, apoptosis, cytoskeleton structure and stress response in the copepod Calanus helgolandicus. Of the 18 transcripts analyzed by RT-qPCR at least 50% were strongly down-regulated (aldehyde dehydrogenase 9, 8 and 6, cellular apoptosis susceptibility and inhibitor of apoptosis IAP proteins, heat shock protein 40, alpha- and beta-tubulins) compared to animals fed on a weak oxylipin-producing diet (Chaetoceros socialis) which showed no changes in gene expression profiles. CONCLUSIONS: Our results provide molecular evidence of the toxic effects of strong oxylipin-producing diatoms on grazers, showing that primary defense systems that should be activated to protect copepods against toxic algae can be inhibited. On the other hand other classical detoxification genes (glutathione S transferase, superoxide dismutase, catalase, cytochrome P450) were not affected possibly due to short exposure times. Given the importance of diatom blooms in nutrient-rich aquatic environments these results offer a plausible explanation for the inefficient use of a potentially valuable food resource, the spring diatom bloom, by some copepod species. PMID- 22046382 TI - Barriers to participation in a patient satisfaction survey: who are we missing? AB - BACKGROUND: A common weakness of patient satisfaction surveys is a suboptimal participation rate. Some patients may be unable to participate, because of language barriers, physical limitations, or mental problems. As the role of these barriers is poorly understood, we aimed to identify patient characteristics that are associated with non-participation in a patient satisfaction survey. METHODOLOGY: At the University Hospitals of Geneva, Switzerland, a patient satisfaction survey is regularly conducted among all adult patients hospitalized for >24 hours on a one-month period in the departments of internal medicine, geriatrics, surgery, neurosciences, psychiatry, and gynaecology-obstetrics. In order to assess the factors associated with non-participation to the patient satisfaction survey, a case-control study was conducted among patients selected for the 2005 survey. Cases (non respondents, n = 195) and controls (respondents, n = 205) were randomly selected from the satisfaction survey, and information about potential barriers to participation was abstracted in a blinded fashion from the patients' medical and nursing charts. PRINCIPAL FINDINGS: Non participation in the satisfaction survey was independently associated with the presence of a language barrier (odds ratio [OR] 4.53, 95% confidence interval [CI95%]: 2.14-9.59), substance abuse (OR 3.75, CI95%: 1.97-7.14), cognitive limitations (OR 3.72, CI95%: 1.64-8.42), a psychiatric diagnosis (OR 1.99, CI95%: 1.23-3.23) and a sight deficiency (OR 2.07, CI95%: 0.98-4.36). The odds ratio for non-participation increased gradually with the number of predictors. CONCLUSIONS: Five barriers to non-participation in a mail survey were identified. Gathering patient feedback through mailed surveys may lead to an under-representation of some patient subgroups. PMID- 22046383 TI - Distinct origin of the Y and St genome in Elymus species: evidence from the analysis of a large sample of St genome species using two nuclear genes. AB - BACKGROUND: Previous cytological and single copy nuclear genes data suggested the St and Y genome in the StY-genomic Elymus species originated from different donors: the St from a diploid species in Pseudoroegneria and the Y from an unknown diploid species, which are now extinct or undiscovered. However, ITS data suggested that the Y and St genome shared the same progenitor although rather few St genome species were studied. In a recent analysis of many samples of St genome species Pseudoroegneria spicata (Pursh) A. Love suggested that one accession of P. spicata species was the most likely donor of the Y genome. The present study tested whether intraspecific variation during sampling could affect the outcome of analyses to determining the origin of Y genome in allotetraploid StY species. We also explored the evolutionary dynamics of these species. METHODOLOGY/PRINCIPAL FINDINGS: Two single copy nuclear genes, the second largest subunit of RNA polymerase II (RPB2) and the translation elongation factor G (EF G) sequences from 58 accessions of Pseudoroegneria and Elymus species, together with those from Hordeum (H), Agropyron (P), Australopyrum (W), Lophopyrum (E(e)), Thinopyrum (E(a)), Thinopyrum (E(b)), and Dasypyrum (V) were analyzed using maximum parsimony, maximum likelihood and Bayesian methods. Sequence comparisons among all these genomes revealed that the St and Y genomes are relatively dissimilar. Extensive sequence variations have been detected not only between the sequences from St and Y genome, but also among the sequences from diploid St genome species. Phylogenetic analyses separated the Y sequences from the St sequences. CONCLUSIONS/SIGNIFICANCE: Our results confirmed that St and Y genome in Elymus species have originated from different donors, and demonstrated that intraspecific variation does not affect the identification of genome origin in polyploids. Moreover, sequence data showed evidence to support the suggestion of the genome convergent evolution in allopolyploid StY genome species. PMID- 22046384 TI - Multidimensional poverty and child survival in India. AB - BACKGROUND: Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations) and included in the development agenda, its measurement and application are still limited. OBJECTIVES AND METHODOLOGY: Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses. RESULTS: The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed. CONCLUSION: Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population. PMID- 22046385 TI - Loss of the alpha2beta1 integrin alters human papilloma virus-induced squamous carcinoma progression in vivo and in vitro. AB - Expression of the alpha2beta1 integrin, a receptor for collagens and laminin, is altered during tumor progression. Recent studies have linked polymorphisms in the alpha2 integrin gene with oral, squamous cell carcinoma (SCC). To determine the alpha2beta1 integrin's role in SCC progression, we crossed alpha2-null mice with K14-HPV16 transgenic animals. Pathological progression to invasive carcinoma was evaluated in HPV-positive, alpha2-null (HPV/KO) and HPV-positive, wild-type (HPV/WT) animals. alpha2beta1 integrin expression stimulated progression from hyperplasia and papillomatosis to dysplasia with concomitant dermal mast cell infiltration. Moreover, lymph node metastasis was decreased by 31.3% in HPV/KO, compared to HPV/WT, animals. To evaluate the integrin-specific impact on the malignant epithelium versus the microenvironment, we developed primary tumor cell lines. Although transition from dysplasia to carcinoma was unaltered during spontaneous tumor development, isolated primary HPV/KO SCC cell lines demonstrated decreased migration and invasion, compared to HPV/WT cells. When HPV/WT and HPV/KO SCC cells were orthotopically injected into WT or KO hosts, tumor alpha2beta1 integrin expression resulted in decreased tumor latency, regardless of host integrin status. HPV/WT SCC lines failed to demonstrate a proliferative advantage in vitro, however, the HPV/WT tumors demonstrated increased growth compared to HPV/KO SCC lines in vivo. Although contributions of the integrin to the microenvironment cannot be excluded, our studies indicate that alpha2beta1 integrin expression by HPV-transformed keratinocytes modulates SCC growth and progression. PMID- 22046386 TI - Evaluation of type-specific real-time PCR assays using the LightCycler and J.B.A.I.D.S. for detection of adenoviruses in species HAdV-C. AB - Sporadically, HAdVs from species HAdV-C are detected in acute respiratory disease outbreaks. To rapidly type these viruses, we designed real-time PCR assays that detect and discriminate between adenovirus types HAdV-C1, -C2, -C5, and -C6. Sixteen clinical isolates from the California Department of Public Health were used to validate the new assays. Type-specific TaqMan real-time PCR assays were designed and used independently to successfully identify 16 representative specimens. The lower limit of detection for our LightCycler singleplex real-time PCR assays were calculated to be 100, 100, 100, and 50 genomic copies per reaction for HAdV-C1, HAdV-C2, HAdV-C5 and HAdV-C6, respectively. The results for the singleplex J.B.A.I.D.S. assays were similar. Our assays did not cross-react with other adenoviruses outside of species HAdV-C, respiratory syncytial virus, influenza, or respiratory disease causing bacteria. These assays have the potential to be useful as diagnostic tools for species HAdV-C infection. PMID- 22046387 TI - Behavioural correlate of choice confidence in a discrete trial paradigm. AB - How animals make choices in a changing and often uncertain environment is a central theme in the behavioural sciences. There is a substantial literature on how animals make choices in various experimental paradigms but less is known about the way they assess a choice after it has been made in terms of the expected outcome. Here, we used a discrete trial paradigm to characterise how the reward history shaped the behaviour on a trial by trial basis. Rats initiated each trial which consisted of a choice between two drinking spouts that differed in their probability of delivering a sucrose solution. Critically, sucrose was delivered after a delay from the first lick at the spouts--this allowed us to characterise the behavioural profile during the window between the time of choice and its outcome. Rats' behaviour converged to optimum choice, both during the acquisition phase and after the reversal of contingencies. We monitored the post choice behaviour at a temporal precision of 1 millisecond; lick-response profiles revealed that rats spent more time at the spout with the higher reward probability and exhibited a sparser lick pattern. This was the case when we exclusively examined the unrewarded trials, where the outcome was identical. The differential licking profiles preceded the differential choice ratios and could thus predict the changes in choice behaviour. PMID- 22046388 TI - Urinary bisphenol A and type-2 diabetes in U.S. adults: data from NHANES 2003 2008. AB - OBJECTIVE: Bisphenol A (BPA) is found in plastics and other consumer products; exposure may lead to insulin resistance and development of type-2 diabetes mellitus (T2DM) through over-activation of pancreatic beta-cells. Previous studies using data from the National Health and Nutrition Examination Survey (NHANES) showed an inconsistent association between prevalence of self-reported T2DM and urinary BPA. We used a different diagnosis method of T2DM (hemoglobin A1c (HbA1c)) with a larger subset of NHANES. METHODS AND FINDINGS: We analyzed data from 4,389 adult participants who were part of a sub-study of environmental phenol measurements in urine from three NHANES cycles from 2003 to 2008. T2DM was defined as having a HbA1c >= 6.5% or use of diabetes medication. The weighted prevalence of T2DM was 9.2%. Analysis of the total sample revealed that a two fold increase in urinary BPA was associated with an odds ratio (OR) of 1.08 of T2DM (95% confidence interval (CI), 1.02 to 1.16), after controlling for potential confounders. However, when we examined each NHANES cycle individually, we only found a statistically significant association in the 2003/04 cycle (n = 1,364, OR = 1.23 (95% CI, 1.07 to 1.42) for each doubling in urinary BPA). We found no association in either the NHANES cycle from 2005/06 (n = 1,363, OR = 1.05 (95% CI, 0.94 to 1.18)); or 2007/08 (n = 1,662, OR = 1.06 (95% CI, 0.91 to 1.23)). Similar patterns of associations between BPA and continuous HbA1c were also observed. CONCLUSIONS: Although higher urinary BPA was associated with elevated HbA1c and T2DM in the pooled analysis, it was driven by data from only one NHANES cycle. Additional studies, especially of a longitudinal design with repeated BPA measurements, are needed to further elucidate the association between BPA and T2DM. PMID- 22046389 TI - Aerosolized human extracellular superoxide dismutase prevents hyperoxia-induced lung injury. AB - An important issue in critical care medicine is the identification of ways to protect the lungs from oxygen toxicity and reduce systemic oxidative stress in conditions requiring mechanical ventilation and high levels of oxygen. One way to prevent oxygen toxicity is to augment antioxidant enzyme activity in the respiratory system. The current study investigated the ability of aerosolized extracellular superoxide dismutase (EC-SOD) to protect the lungs from hyperoxic injury. Recombinant human EC-SOD (rhEC-SOD) was produced from a synthetic cassette constructed in the methylotrophic yeast Pichia pastoris. Female CD-1 mice were exposed in hyperoxia (FiO2>95%) to induce lung injury. The therapeutic effects of EC-SOD and copper-zinc SOD (CuZn-SOD) via an aerosol delivery system for lung injury and systemic oxidative stress at 24, 48, 72 and 96 h of hyperoxia were measured by bronchoalveolar lavage, wet/dry ratio, lung histology, and 8-oxo 2'-deoxyguanosine (8-oxo-dG) in lung and liver tissues. After exposure to hyperoxia, the wet/dry weight ratio remained stable before day 2 but increased significantly after day 3. The levels of oxidative biomarker 8-oxo-dG in the lung and liver were significantly decreased on day 2 (P<0.01) but the marker in the liver increased abruptly after day 3 of hyperoxia when the mortality increased. Treatment with aerosolized rhEC-SOD increased the survival rate at day 3 under hyperoxia to 95.8%, which was significantly higher than that of the control group (57.1%), albumin treated group (33.3%), and CuZn-SOD treated group (75%). The protective effects of EC-SOD against hyperoxia were further confirmed by reduced lung edema and systemic oxidative stress. Aerosolized EC-SOD protected mice against oxygen toxicity and reduced mortality in a hyperoxic model. The results encourage the use of an aerosol therapy with EC-SOD in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure, including acute respiratory distress syndrome (ARDS). PMID- 22046390 TI - Evolutionary consequences of altered atmospheric oxygen in Drosophila melanogaster. AB - Twelve replicate populations of Drosophila melanogaster, all derived from a common ancestor, were independently evolved for 34+ generations in one of three treatment environments of varying PO(2): hypoxia (5.0-10.1 kPa), normoxia (21.3 kPa), and hyperoxia (40.5 kPa). Several traits related to whole animal performance and metabolism were assayed at various stages via "common garden" and reciprocal transplant assays to directly compare evolved and acclimatory differences among treatments. Results clearly demonstrate the evolution of a greater tolerance to acute hypoxia in the hypoxia-evolved populations, consistent with adaptation to this environment. Greater hypoxia tolerance was associated with an increase in citrate synthase activity in fly homogenate when compared to normoxic (control) populations, suggesting an increase in mitochondrial volume density in these populations. In contrast, no direct evidence of increased performance of the hyperoxia-evolved populations was detected, although a significant decrease in the tolerance of these populations to acute hypoxia suggests a cost to adaptation to hyperoxia. Hyperoxia-evolved populations had lower productivity overall (i.e., across treatment environments) and there was no evidence that hypoxia or hyperoxia-evolved populations had greatest productivity or longevity in their respective treatment environments, suggesting that these assays failed to capture the components of fitness relevant to adaptation. PMID- 22046391 TI - Population attributable risk of unintentional childhood poisoning in Karachi Pakistan. AB - BACKGROUND: The percentage of unintentional childhood poisoning cases in a given population attributable to specific risk factors (i.e., the population attributable risk) which can be calculated; determination of such risk factors associated with potentially modifiable risk factors, are necessary to focus on the prevention strategies. METHODS: We calculated PARs, using 120 cases with unintentional poisoning and 360 controls in a hospital based matched case- control study. The risk factors were accessibility to hazardous chemicals and medicines due to unsafe storage, child behavior reported as hyperactive, storage of kerosene and petroleum in soft drink bottles, low socioeconomic class, less education of the mother and the history of previous poisoning. RESULTS: THE FOLLOWING ATTRIBUTED RISKS WERE OBSERVED: 12% (95% confidence interval [CI] = 8% 16%) for both chemicals and medicines stored unsafe, 19% (15%-23%) for child reported as hyperactive, 40% (38%-42%) for storage of kerosene and petroleum in soft drink bottles, 48% (42%-54%) for low socioeconomic status, 38% (32%-42%) for no formal mothers education and 5.8% (2%-10%) for history of previous poisoning. 48% of cases for overall study population which could be attributed to at least one of the six risk factors. Among girls, this proportion was 23% and 43% among boys. About half of the unintentional childhood poisoning cases in this Pakistani population could be avoided. CONCLUSION: Exposure to potentially modifiable risk indicators explained about half of the cases of unintentional poisoning among children under five years of age in this Pakistani population, indicating the theoretical scope for prevention of the disease. PMID- 22046393 TI - Tissue-restricted expression of Nrf2 and its target genes in zebrafish with gene specific variations in the induction profiles. AB - The Keap1-Nrf2 system serves as a defense mechanism against oxidative stress and electrophilic toxicants by inducing more than one hundred cytoprotective proteins, including antioxidants and phase 2 detoxifying enzymes. Since induction profiles of Nrf2 target genes have been studied exclusively in cultured cells, and not in animal models, their tissue-specificity has not been well characterized. In this paper, we examined and compared the tissue-specific expression of several Nrf2 target genes in zebrafish larvae by whole-mount in situ hybridization (WISH). Seven zebrafish genes (gstp1, mgst3b, prdx1, frrs1c, fthl, gclc and hmox1a) suitable for WISH analysis were selected from candidates for Nrf2 targets identified by microarray analysis. Tissue-restricted induction was observed in the nose, gill, and/or liver for all seven genes in response to Nrf2-activating compounds, diethylmaleate (DEM) and sulforaphane. The Nrf2 gene itself was dominantly expressed in these three tissues, implying that tissue restricted induction of Nrf2 target genes is defined by tissue-specific expression of Nrf2. Interestingly, the induction of frrs1c and gclc in liver and nose, respectively, was quite low and that of hmox1a was restricted in the liver. These results indicate the existence of gene-specific variations in the tissue specificity, which can be controlled by factors other than Nrf2. PMID- 22046392 TI - Screening for active small molecules in mitochondrial complex I deficient patient's fibroblasts, reveals AICAR as the most beneficial compound. AB - Congenital deficiency of the mitochondrial respiratory chain complex I (CI) is a common defect of oxidative phosphorylation (OXPHOS). Despite major advances in the biochemical and molecular diagnostics and the deciphering of CI structure, function assembly and pathomechanism, there is currently no satisfactory cure for patients with mitochondrial complex I defects. Small molecules provide one feasible therapeutic option, however their use has not been systematically evaluated using a standardized experimental system. In order to evaluate potentially therapeutic compounds, we set up a relatively simple system measuring different parameters using only a small amount of patient's fibroblasts, in glucose free medium, where growth is highly OXPOS dependent. Ten different compounds were screened using fibroblasts derived from seven CI patients, harboring different mutations.5-Aminoimidazole-4-carboxamide ribotide (AICAR) was found to be the most beneficial compound improving growth and ATP content while decreasing ROS production. AICAR also increased mitochondrial biogenesis without altering mitochondrial membrane potential (Deltapsi). Fluorescence microscopy data supported increased mitochondrial biogenesis and activation of the AMP activated protein kinase (AMPK). Other compounds such as; bezafibrate and oltipraz were rated as favorable while polyphenolic phytochemicals (resverastrol, grape seed extract, genistein and epigallocatechin gallate) were found not significant or detrimental. Although the results have to be verified by more thorough investigation of additional OXPHOS parameters, preliminary rapid screening of potential therapeutic compounds in individual patient's fibroblasts could direct and advance personalized medical treatment. PMID- 22046394 TI - Predictors of limb fat gain in HIV positive patients following a change to tenofovir-emtricitabine or abacavir-lamivudine. AB - BACKGROUND: Antiretroviral treatment (cART) in HIV causes lipoatrophy. We examined predictors of anthropometric outcomes over 96 weeks in HIV-infected, lipoatrophic adults receiving stable cART randomised to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) fixed dose combinations. METHODOLOGY/PRINCIPAL FINDINGS: The STEAL study was a prospective trial of virologically suppressed participants randomised to either TDF-FTC (n = 178) or ABC-3TC (n = 179). Anthropometric assessment was conducted at baseline, weeks 48 and 96. The analysis population included those with baseline and week 96 data remaining on randomised therapy. Distribution of limb fat change was divided into four categories (<= 0%, >0-10%, >10-20%, >20%). Baseline characteristics [demographics, medical history, metabolic and cardiovascular biomarkers] were assessed as potential predictors of change in percent subcutaneous limb fat using linear regression. 303 participants (85% of STEAL population) were included. Baseline characteristics were: mean (+/- SD) age 45 (+/- 8) years; thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI) duration 4 (+/- 3) years; limb fat 5.4 (+/- 3.0)kg; body mass index 24.7 (+/- 3 .5) kg/m(2). Mean (SD) limb fat gain to week 48 and 96 was 7.6% (+/- 22.4) and 13.2% (+/- 27.3), respectively, with no significant difference between groups. 51.5% of all participants had >10% gain in limb fat. Predictors of greater limb fat gain at week 96 were baseline tNRTI (10.3, p = 0.001), glucose >6 mmol/L (16.1, p = 0.04), higher interleukin 6 (IL-6) (2.8, p = 0.004) and lower baseline limb fat (3.8-6.4 kg - 11.2; >6.4 kg - 15.7, p trend<0.001). CONCLUSIONS/SIGNIFICANCE: Modest peripheral fat gain occurred with both TDF-FTC and ABC-3TC. Baseline factors associated with more severe lipodystrophy (lipoatrophy, baseline tNRTI, raised IL6, and glucose) predicted greater limb fat recovery at 96 weeks. PMID- 22046395 TI - Venom of parasitoid, Pteromalus puparum, suppresses host, Pieris rapae, immune promotion by decreasing host C-type lectin gene expression. AB - BACKGROUND: Insect hosts have evolved immunity against invasion by parasitoids, and in co-evolutionary response parasitoids have also developed strategies to overcome host immune systems. The mechanisms through which parasitoid venoms disrupt the promotion of host immunity are still unclear. We report here a new mechanism evolved by parasitoid Pteromalus puparum, whose venom inhibited the promotion of immunity in its host Pieris rapae (cabbage white butterfly). METHODOLOGY/PRINCIPAL FINDINGS: A full-length cDNA encoding a C-type lectin (Pr CTL) was isolated from P. rapae. Quantitative PCR and immunoblotting showed that injection of bacterial and inert beads induced expression of Pr-CTL, with peaks of mRNA and Pr-CTL protein levels at 4 and 8 h post beads challenge, respectively. In contrast, parasitoid venom suppressed Pr-CTL expression when co injected with beads, in a time and dose-dependent manner. Immunolocalization and immunoblotting results showed that Pr-CTL was first detectable in vesicles present in cytoplasm of granulocytes in host hemolymph, and was then secreted from cells into circulatory fluid. Finally, the secreted Pr-CTL bound to cellular membranes of both granulocytes and plasmatocytes. Injection of double-stranded RNA specific for target gene decreased expression of Pr-CTL, and a few other host immune-related genes. Suppression of Pr-CTL expression also down-regulated antimicrobial and phenoloxidase activities, and reducing phagocytotic and encapsulation rates in host. The inhibitory effect of parasitoid venom on host encapsulation is consistent with its effect in suppressing Pr-CTL expression. Binding assay results showed that recombinant Pr-CTL directly attached to the surface of P. puparum egges. We infer that Pr-CTL may serve as an immune signalling co-effector, first binding to parasitoid eggs, regulating expression of a set of immune-related genes and promoting host immunity. CONCLUSIONS/SIGNIFICANCE: P. puparum venom inhibits promotion of host immune responses by silencing expression of host C-type lectin gene Pr-CTL, whose expression affected transcription of other host immune-related genes. PMID- 22046396 TI - High-throughput analysis of calcium signalling kinetics in astrocytes stimulated with different neurotransmitters. AB - Astrocytes express a wide range of receptors for neurotransmitters and hormones that are coupled to increases in intracellular Ca(2+) concentration, enabling them to detect activity in both neuronal and vascular networks. There is increasing evidence that astrocytes are able to discriminate between different Ca(2+)-linked stimuli, as the efficiency of some Ca(2+) dependent processes- notably release of gliotransmitters--depends on the stimulus that initiates the Ca(2+) signal. The spatiotemporal complexity of Ca(2+) signals is substantial, and we here tested the hypothesis that variation in the kinetics of Ca(2+) responses could offer a means of selectively engaging downstream targets, if agonists exhibited a "signature shape" in evoked Ca(2+) response. To test this, astrocytes were exposed to three different receptor agonists (ATP, glutamate and histamine) and the resultant Ca(2+) signals were analysed for systematic differences in kinetics that depended on the initiating stimulus. We found substantial heterogeneity between cells in the time course of Ca(2+) responses, but the variation did not correlate with the type or concentration of the stimulus. Using a simple metric to quantify the extent of difference between populations, it was found that the variation between agonists was insufficient to allow signal discrimination. We conclude that the time course of global intracellular Ca(2+) signals does not offer the cells a means for distinguishing between different neurotransmitters. PMID- 22046397 TI - Validity of verbal autopsy procedures for determining malaria deaths in different epidemiological settings in Uganda. AB - BACKGROUND: Verbal autopsy (VA) procedures can be used to estimate cause of death in settings with inadequate vital registries. However, the sensitivity of VA for determining malaria-specific mortality may be low, and may vary with transmission intensity. We assessed the diagnostic accuracy of VA procedures as compared to hospital medical records for determining cause of death in children under five in three different malaria transmission settings in Uganda, including Tororo (high), Kampala (medium), and Kisoro (low). METHODS AND FINDINGS: Caretakers of children who died in participating hospitals were interviewed using a standardized World Health Organization questionnaire. Medical records from the child's hospitalization were also reviewed. Causes of death based on the VA questionnaires and the medical records were assigned independently by physician reviewers and then compared. A total of 719 cases were included in the final analysis, 67 in Tororo, 600 in Kampala, and 52 in Kisoro. Malaria was classified as the underlying or contributory cause of death by review of medical records in 33 deaths in Tororo, 60 in Kampala, and 0 in Kisoro. The sensitivity of VA procedures for determining malaria deaths in Tororo was 61% (95% CI 44-78%) and 50% in Kampala (95% CI 37-63%). Specificity for determining malaria deaths in Tororo and Kampala was high (>88%), but positive predictive value varied widely, from 83% in Tororo to 34% in Kampala (difference 49%, 95% CI 31-67, p<0.001). The difference between the cause-specific mortality fraction for malaria as determined by VA procedures and medical records was -11% in Tororo, +5% in Kampala, and +14% in Kisoro. CONCLUSIONS: Our results suggest that these VA methods have an acceptable level of diagnostic accuracy for determining malaria deaths at the population level in high and medium transmission areas, but not in low transmission areas. PMID- 22046398 TI - Grooming coercion and the post-conflict trading of social services in wild Barbary macaques. AB - In animal and human societies, social services such as protection from predators are often exchanged between group members. The tactics that individuals display to obtain a service depend on its value and on differences between individuals in their capacity to aggressively obtain it. Here we analysed the exchange of valuable social services (i.e. grooming and relationship repair) in the aftermath of a conflict, in wild Barbary macaques (Macaca sylvanus). The relationship repair function of post-conflict affiliation (i.e. reconciliation) was apparent in the victim but not in the aggressor. Conversely, we found evidence for grooming coercion by the aggressor; when the victim failed to give grooming soon after a conflict they received renewed aggression from the aggressor. We argue that post-conflict affiliation between former opponents can be better described as a trading of social services rather than coercion alone, as both animals obtain some benefits (i.e. grooming for the aggressor and relationship repair for the victim). Our study is the first to test the importance of social coercion in the aftermath of a conflict. Differences in competitive abilities can affect the exchange of services and the occurrence of social coercion in animal societies. This may also help explain the variance between populations and species in their social behaviour and conflict management strategies. PMID- 22046399 TI - Lrp acts as both a positive and negative regulator for type 1 fimbriae production in Salmonella enterica serovar Typhimurium. AB - Leucine-responsive regulatory protein (Lrp) is known to be an indirect activator of type 1 fimbriae synthesis in Salmonella enterica serovar Typhimurium via direct regulation of FimZ, a direct positive regulator for type 1 fimbriae production. Using RT-PCR, we have shown previously that fimA transcription is dramatically impaired in both lrp-deletion (Deltalrp) and constitutive-lrp expression (lrp(C)) mutant strains. In this work, we used chromosomal P(fimA) lacZ fusions and yeast agglutination assays to confirm and extend our previous results. Direct binding of Lrp to P(fimA) was shown by an electrophoretic mobility shift assay (EMSA) and DNA footprinting assay. Site-directed mutagenesis revealed that the Lrp-binding motifs in P(fimA) play a role in both activation and repression of type 1 fimbriae production. Overproduction of Lrp also abrogates fimZ expression. EMSA data showed that Lrp and FimZ proteins independently bind to P(fimA) without competitive exclusion. In addition, both Lrp and FimZ binding to P(fimA) caused a hyper retardation (supershift) of the DNA-protein complex compared to the shift when each protein was present alone. Nutrition-dependent cellular Lrp levels closely correlated with the amount of type 1 fimbriae production. These observations suggest that Lrp plays important roles in type 1 fimbriation by acting as both a positive and negative regulator and its effect depends, at least in part, on the cellular concentration of Lrp in response to the nutritional environment. PMID- 22046400 TI - Modulation ofTcf7l2 expression alters behavior in mice. AB - The comorbidity of type 2 diabetes (T2D) with several psychiatric diseases is well established. While environmental factors may partially account for these co occurrences, common genetic susceptibilities could also be implicated in the confluence of these diseases. In support of shared genetic burdens, TCF7L2, the strongest genetic determinant for T2D risk in the human population, has been recently implicated in schizophrenia (SCZ) risk, suggesting that this may be one of many loci that pleiotropically influence both diseases. To investigate whether Tcf7l2 is involved in behavioral phenotypes in addition to its roles in glucose metabolism, we conducted several behavioral tests in mice with null alleles of Tcf7l2 or overexpressing Tcf7l2. We identified a role for Tcf7l2 in anxiety-like behavior and a dose-dependent effect of Tcf7l2 alleles on fear learning. None of the mutant mice showed differences in prepulse inhibition (PPI), which is a well established endophenotype for SCZ. These results show that Tcf7l2 alters behavior in mice. Importantly, these differences are observed prior to the onset of detectable glucose metabolism abnormalities. Whether these differences are related to human anxiety-disorders or schizophrenia remains to be determined. These animal models have the potential to elucidate the molecular basis of psychiatric comorbidities in diabetes and should therefore be studied further. PMID- 22046401 TI - Fatty-acid preference changes during development in Drosophila melanogaster. AB - Fatty-acids (FAs) are required in the diet of many animals throughout their life. However, the mechanisms involved in the perception of and preferences for dietary saturated and unsaturated FAs (SFAs and UFAs, respectively) remain poorly explored, especially in insects. Using the model species Drosophila melanogaster, we measured the responses of wild-type larvae and adults to pure SFAs (14, 16, and 18 carbons) and UFAs (C18 with 1, 2, or 3 double-bonds). Individual and group behavioral tests revealed different preferences in larvae and adults. Larvae preferred UFAs whereas SFAs tended to induce both a strong aversion and a persistent aggregation behavior. Adults generally preferred SFAs, and laid more eggs and had a longer life span when ingesting these substances as compared to UFAs. Our data suggest that insects can discriminate long-chain dietary FAs. The developmental change in preference shown by this species might reflect functional variation in use of FAs or stage-specific nutritional requirements, and may be fundamental for insect use of these major dietary components. PMID- 22046402 TI - Methanosarcina acetivorans C2A topoisomerase IIIalpha, an archaeal enzyme with promiscuity in divalent cation dependence. AB - Topoisomerases play a fundamental role in genome stability, DNA replication and repair. As a result, topoisomerases have served as therapeutic targets of interest in Eukarya and Bacteria, two of the three domains of life. Since members of Archaea, the third domain of life, have not been implicated in any diseased state to-date, there is a paucity of data on archaeal topoisomerases. Here we report Methanosarcina acetivorans TopoIIIalpha (MacTopoIIIalpha) as the first biochemically characterized mesophilic archaeal topoisomerase. Maximal activity for MacTopoIIIalpha was elicited at 30-35 degrees C and 100 mM NaCl. As little as 10 fmol of the enzyme initiated DNA relaxation, and NaCl concentrations above 250 mM inhibited this activity. The present study also provides the first evidence that a type IA Topoisomerase has activity in the presence of all divalent cations tested (Mg(2+), Ca(2+), Sr(2+), Ba(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+) and Cd(2+)). Activity profiles were, however, specific to each metal. Known type I (ssDNA and camptothecin) and type II (etoposide, novobiocin and nalidixic acid) inhibitors with different mechanisms of action were used to demonstrate that MacTopoIIIalpha is a type IA topoisomerase. Alignment of MacTopoIIIalpha with characterized topoisomerases identified Y317 as the putative catalytic residue, and a Y317F mutation ablated DNA relaxation activity, demonstrating that Y317 is essential for catalysis. As the role of Domain V (C terminal domain) is unclear, MacTopoIIIalpha was aligned with the canonical E. coli TopoI 67 kDa fragment in order to construct an N-terminal (1-586) and a C terminal (587-752) fragment for analysis. Activity could neither be elicited from the fragments individually nor reconstituted from a mixture of the fragments, suggesting that native folding is impaired when the two fragments are expressed separately. Evidence that each of the split domains plays a role in Zn(2+) binding of the enzyme is also provided. PMID- 22046403 TI - Investigation of variation in gene expression profiling of human blood by extended principle component analysis. AB - BACKGROUND: Human peripheral blood is a promising material for biomedical research. However, various kinds of biological and technological factors result in a large degree of variation in blood gene expression profiles. METHODOLOGY/PRINCIPAL FINDINGS: Human peripheral blood samples were drawn from healthy volunteers and analysed using the Human Genome U133Plus2 Microarray. We applied a novel approach using the Principle Component Analysis and Eigen-R(2) methods to dissect the overall variation of blood gene expression profiles with respect to the interested biological and technological factors. The results indicated that the predominating sources of the variation could be traced to the individual heterogeneity of the relative proportions of different blood cell types (leukocyte subsets and erythrocytes). The physiological factors like age, gender and BMI were demonstrated to be associated with 5.3% to 9.2% of the total variation in the blood gene expression profiles. We investigated the gene expression profiles of samples from the same donors but with different levels of RNA quality. Although the proportion of variation associated to the RNA Integrity Number was mild (2.1%), the significant impact of RNA quality on the expression of individual genes was observed. CONCLUSIONS: By characterizing the major sources of variation in blood gene expression profiles, such variability can be minimized by modifications to study designs. Increasing sample size, balancing confounding factors between study groups, using rigorous selection criteria for sample quality, and well controlled experimental processes will significantly improve the accuracy and reproducibility of blood transcriptome study. PMID- 22046404 TI - Rates of mutation and host transmission for an Escherichia coli clone over 3 years. AB - Although over 50 complete Escherichia coli/Shigella genome sequences are available, it is only for closely related strains, for example the O55:H7 and O157:H7 clones of E. coli, that we can assign differences to individual evolutionary events along specific lineages. Here we sequence the genomes of 14 isolates of a uropathogenic E. coli clone that persisted for 3 years within a household, including a dog, causing a urinary tract infection (UTI) in the dog after 2 years. The 20 mutations observed fit a single tree that allows us to estimate the mutation rate to be about 1.1 per genome per year, with minimal evidence for adaptive change, including in relation to the UTI episode. The host data also imply at least 6 host transfer events over the 3 years, with 2 lineages present over much of that period. To our knowledge, these are the first direct measurements for a clone in a well-defined host community that includes rates of mutation and host transmission. There is a concentration of non-synonymous mutations associated with 2 transfers to the dog, suggesting some selection pressure from the change of host. However, there are no changes to which we can attribute the UTI event in the dog, which suggests that this occurrence after 2 years of the clone being in the household may have been due to chance, or some unknown change in the host or environment. The ability of a UTI strain to persist for 2 years and also to transfer readily within a household has implications for epidemiology, diagnosis, and clinical intervention. PMID- 22046405 TI - The interaction between the first transmembrane domain and the thumb of ASIC1a is critical for its N-glycosylation and trafficking. AB - Acid-sensing ion channel-1a (ASIC1a), the primary proton receptor in the brain, contributes to multiple diseases including stroke, epilepsy and multiple sclerosis. Thus, a better understanding of its biogenesis will provide important insights into the regulation of ASIC1a in diseases. Interestingly, ASIC1a contains a large, yet well organized ectodomain, which suggests the hypothesis that correct formation of domain-domain interactions at the extracellular side is a key regulatory step for ASIC1a maturation and trafficking. We tested this hypothesis here by focusing on the interaction between the first transmembrane domain (TM1) and the thumb of ASIC1a, an interaction known to be critical in channel gating. We mutated Tyr71 and Trp287, two key residues involved in the TM1 thumb interaction in mouse ASIC1a, and found that both Y71G and W287G decreased synaptic targeting and surface expression of ASIC1a. These defects were likely due to altered folding; both mutants showed increased resistance to tryptic cleavage, suggesting a change in conformation. Moreover, both mutants lacked the maturation of N-linked glycans through mid to late Golgi. These data suggest that disrupting the interaction between TM1 and thumb alters ASIC1a folding, impedes its glycosylation and reduces its trafficking. Moreover, reducing the culture temperature, an approach commonly used to facilitate protein folding, increased ASIC1a glycosylation, surface expression, current density and slowed the rate of desensitization. These results suggest that correct folding of extracellular ectodomain plays a critical role in ASIC1a biogenesis and function. PMID- 22046406 TI - Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese. AB - BACKGROUND: Several novel susceptibility loci for type 2 diabetes have been identified through genome-wide association studies (GWAS) for type 2 diabetes or quantitative traits related to glucose metabolism in European populations. To investigate the association of the 13 new European GWAS-derived susceptibility loci with type 2 diabetes in the Japanese population, we conducted a replication study using 3 independent Japanese case-control studies. METHODOLOGY/PRINCIPAL FINDINGS: We examined the association of single nucleotide polymorphisms (SNPs) within 13 loci (MTNR1B, GCK, IRS1, PROX1, BCL11A, ZBED3, KLF14, TP53INP1, KCNQ1, CENTD2, HMGA2, ZFAND6 and PRC1) with type 2 diabetes using 4,964 participants (2,839 cases and 2,125 controls) from 3 independent Japanese samples. The association of each SNP with type 2 diabetes was analyzed by logistic regression analysis. Further, we performed combined meta-analyses for the 3 studies and previously performed Japanese GWAS data (4,470 cases vs. 3,071 controls). The meta-analysis revealed that rs2943641 in the IRS1 locus was significantly associated with type 2 diabetes, (P = 0.0034, OR = 1.15 95% confidence interval; 1.05-1.26) and 3 SNPs, rs10930963 in the MTNR1B locus, rs972283 in the KLF14 locus, and rs231362 in the KCNQ1 locus, had nominal association with type 2 diabetes in the present Japanese samples (P<0.05). CONCLUSIONS: These results indicate that IRS1 locus may be common locus for type 2 diabetes across different ethnicities. PMID- 22046407 TI - Thymosin beta 4 prevents oxidative stress by targeting antioxidant and anti apoptotic genes in cardiac fibroblasts. AB - RATIONALE: Thymosin beta-4 (Tbeta4) is a ubiquitous protein with diverse functions relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory responses. The effecter molecules targeted by Tbeta4 for cardiac protection remains unknown. The purpose of this study is to determine the molecules targeted by Tbeta4 that mediate cardio-protection under oxidative stress. METHODS: Rat neonatal fibroblasts cells were exposed to hydrogen peroxide (H(2)O(2)) in presence and absence of Tbeta4 and expression of antioxidant, apoptotic and pro-fibrotic genes was evaluated by quantitative real time PCR and western blotting. Reactive oxygen species (ROS) levels were estimated by DCF-DA using fluorescent microscopy and fluorimetry. Selected antioxidant and antiapoptotic genes were silenced by siRNA transfections in cardiac fibroblasts and the effect of Tbeta4 on H(2)O(2)-induced profibrotic events was evaluated. RESULTS: Pre-treatment with Tbeta4 resulted in reduction of the intracellular ROS levels induced by H(2)O(2) in the cardiac fibroblasts. This was associated with an increased expression of antioxidant enzymes Cu/Zn superoxide dismutase (SOD) and catalase and reduction of Bax/Bcl(2) ratio. Tbeta4 treatment reduced the expression of pro-fibrotic genes [connective tissue growth factor (CTGF), collagen type-1 (Col-I) and collagen type-3 (Col-III)] in the cardiac fibroblasts. Silencing of Cu/Zn-SOD and catalase gene triggered apoptotic cell death in the cardiac fibroblasts, which was prevented by treatment with Tbeta4. CONCLUSION: This is the first report that exhibits the targeted molecules modulated by Tbeta4 under oxidative stress utilizing the cardiac fibroblasts. Tbeta4 treatment prevented the profibrotic gene expression in the in vitro settings. Our findings indicate that Tbeta4 selectively targets and upregulates catalase, Cu/Zn-SOD and Bcl(2), thereby, preventing H(2)O(2)-induced profibrotic changes in the myocardium. Further studies are warranted to elucidate the signaling pathways involved in the cardio-protection afforded by Tbeta4. PMID- 22046408 TI - Development of gene expression markers of acute heat-light stress in reef building corals of the genus Porites. AB - Coral reefs are declining worldwide due to increased incidence of climate-induced coral bleaching, which will have widespread biodiversity and economic impacts. A simple method to measure the sub-bleaching level of heat-light stress experienced by corals would greatly inform reef management practices by making it possible to assess the distribution of bleaching risks among individual reef sites. Gene expression analysis based on quantitative PCR (qPCR) can be used as a diagnostic tool to determine coral condition in situ. We evaluated the expression of 13 candidate genes during heat-light stress in a common Caribbean coral Porites astreoides, and observed strong and consistent changes in gene expression in two independent experiments. Furthermore, we found that the apparent return to baseline expression levels during a recovery phase was rapid, despite visible signs of colony bleaching. We show that the response to acute heat-light stress in P. astreoides can be monitored by measuring the difference in expression of only two genes: Hsp16 and actin. We demonstrate that this assay discriminates between corals sampled from two field sites experiencing different temperatures. We also show that the assay is applicable to an Indo-Pacific congener, P. lobata, and therefore could potentially be used to diagnose acute heat-light stress on coral reefs worldwide. PMID- 22046409 TI - Clinical symptoms in fibromyalgia are better associated to lipid peroxidation levels in blood mononuclear cells rather than in plasma. AB - BACKGROUND: We examined lipid peroxidation (LPO) in blood mononuclear cells (BMCs) and plasma, as a marker of oxidative damage, and its association to clinical symptoms in Fibromyalgia (FM) patients. METHODS: We conducted a case control and correlational study comparing 65 patients and 45 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Beck Depression Inventory (BDI). Oxidative stress was determined by measuring LPO in BMCs and plasma. RESULTS: We found increased LPO levels in BMCs and plasma from FM patients as compared to normal control (P<0.001). A significant correlation between LPO in BMCs and clinical parameters was observed (r = 0.584, P<0.001 for VAS; r = 0.823, P<0.001 for FIQ total score; and r = 0.875, P<0.01 for depression in the BDI). We also found a positive correlation between LPO in plasma and clinical symptoms (r = 0.452, P<0.001 for VAS; r = 0.578, P<0.001 for FIQ total score; and r = 0.579, P<0.001 for depression in the BDI). Partial correlation analysis controlling for age and BMI, and sex, showed that both LPO in cells and plasma were independently associated to clinical symptoms. However, LPO in cells, but not LPO in plasma, was independently associated to clinical symptoms when controlling for depression (BDI scores). DISCUSSION: The results of this study suggest a role for oxidative stress in the pathophysiology of fibromyalgia and that LPO in BMCs rather than LPO in plasma is better associated to clinical symptoms in FM. PMID- 22046410 TI - c-Kit-mediated functional positioning of stem cells to their niches is essential for maintenance and regeneration of adult hematopoiesis. AB - The mechanism by which hematopoietic stem and progenitor cells (HSPCs) through interaction with their niches maintain and reconstitute adult hematopoietic cells is unknown. To functionally and genetically track localization of HSPCs with their niches, we employed novel mutant loxPs, lox66 and lox71 and Cre-recombinase technology to conditionally delete c-Kit in adult mice, while simultaneously enabling GFP expression in the c-Kit-deficient cells. Conditional deletion of c Kit resulted in hematopoietic failure and splenic atrophy both at steady state and after marrow ablation leading to the demise of the treated adult mice. Within the marrow, the c-Kit-expressing GFP(+) cells were positioned to Kit ligand (KL) expressing niche cells. This c-Kit-mediated cellular adhesion was essential for long-term maintenance and expansion of HSPCs. These results lay the foundation for delivering KL within specific niches to maintain and restore hematopoiesis. PMID- 22046411 TI - Variation in cooperative behaviour within a single city. AB - Human cooperative behaviour, as assayed by decisions in experimental economic dilemmas such as the Dictator Game, is variable across human populations. Within population variation has been less well studied, especially within industrial societies. Moreover, little is known about the extent to which community-level variation in Dictator Game behaviour relates to community-level variation in real world social behaviour. We chose two neighbourhoods of the city of Newcastle upon Tyne that were similar in most regards, but at opposite ends of the spectrum in terms of level of socioeconomic deprivation. We administered Dictator Games to randomly-selected residents, and also gathered a large number of more naturalistic measures of cooperativeness. There were dramatic differences in Dictator Game behaviour between the two neighbourhoods, with the mean allocation to the other player close to half the stake in the affluent neighbourhood, and close to one tenth of the stake in the deprived neighbourhood. Moreover, the deprived neighbourhood was also characterised by lower self-reported social capital, higher frequencies of crime and antisocial behaviour, a higher frequency of littering, and less willingness to take part in a survey or return a lost letter. On the other hand, there were no differences between the neighbourhoods in terms of the probability of helping a person who dropped an object, needed directions to a hospital, or needed to make change for a coin, and people on the streets were less likely to be alone in the deprived neighbourhood than the affluent one. We conclude that there can be dramatic local differences in cooperative behaviour within the same city, and that these need further theoretical explanation. PMID- 22046412 TI - Novel sex cells and evidence for sex pheromones in diatoms. AB - BACKGROUND: Diatoms belong to the stramenopiles, one of the largest groups of eukaryotes, which are primarily characterized by a presence of an anterior flagellum with tubular mastigonemes and usually a second, smooth flagellum. Based on cell wall morphology, diatoms have historically been divided into centrics and pennates, of which only the former have flagella and only on the sperm. Molecular phylogenies show the pennates to have evolved from among the centrics. However, the timing of flagellum loss--whether before the evolution of the pennate lineage or after--is unknown, because sexual reproduction has been so little studied in the 'araphid' basal pennate lineages, to which Pseudostaurosira belongs. METHODS/PRINCIPAL FINDING: Sexual reproduction of an araphid pennate, Pseudostaurosira trainorii, was studied with light microscopy (including time lapse observations and immunofluorescence staining observed under confocal scanning laser microscopy) and SEM. We show that the species produces motile male gametes. Motility is mostly associated with the extrusion and retrieval of microtubule-based 'threads', which are structures hitherto unknown in stramenopiles, their number varying from one to three per cell. We also report experimental evidence for sex pheromones that reciprocally stimulate sexualization of compatible clones and orientate motility of the male gametes after an initial 'random walk'. CONCLUSIONS/SIGNIFICANCE: The threads superficially resemble flagella, in that both are produced by male gametes and contain microtubules. However, one striking difference is that threads cannot beat or undulate and have no motility of their own, and they do not bear mastigonemes. Threads are sticky and catch and draw objects, including eggs. The motility conferred by the threads is probably crucial for sexual reproduction of P. trainorii, because this diatom is non-motile in its vegetative stage but obligately outbreeding. Our pheromone experiments are the first studies in which gametogenesis has been induced in diatoms by cell-free exudates, opening new possibilities for molecular 'dissection' of sexualization. PMID- 22046413 TI - Human RNA polymerase II-association factor 1 (hPaf1/PD2) regulates histone methylation and chromatin remodeling in pancreatic cancer. AB - Change in gene expression associated with pancreatic cancer could be attributed to the variation in histone posttranslational modifications leading to subsequent remodeling of the chromatin template during transcription. However, the interconnected network of molecules involved in regulating such processes remains elusive. hPaf1/PD2, a subunit of the human PAF-complex, involved in the regulation of transcriptional elongation has oncogenic potential. Our study explores the possibility that regulation of histone methylation by hPaf1 can contribute towards alteration in gene expression by nucleosomal rearrangement. Here, we show that knockdown of hPaf1/PD2 leads to decreased di- and tri methylation at histone H3 lysine 4 residues in pancreatic cancer cells. Interestingly, hPaf1/PD2 colocalizes with MLL1 (Mixed Lineage Leukemia 1), a histone methyltransferase that methylates H3K4 residues. Also, a reduction in hPaf1 level resulted in reduced MLL1 expression and a corresponding decrease in the level of CHD1 (Chromohelicase DNA-binding protein 1), an ATPase dependent chromatin remodeling enzyme that specifically binds to H3K4 di and trimethyl marks. hPaf1/PD2 was also found to interact and colocalize with CHD1 in both cytoplasmic and nuclear extracts of pancreatic cancer cells. Further, reduced level of CHD1 localization in the nucleus in hPaf1/PD2 Knockdown cells could be rescued by ectopic expression of hPaf1/PD2. Micrococcal nuclease digestion showed an altered chromatin structure in hPaf1/PD2-KD cells. Overall, our results suggest that hPaf1/PD2 in association with MLL1 regulates methylation of H3K4 residues, as well as interacts and regulates nuclear shuttling of chromatin remodeling protein CHD1, facilitating its function in pancreatic cancer cells. PMID- 22046414 TI - Analysis of the expression, secretion and translocation of the Salmonella enterica type III secretion system effector SteA. AB - Many Gram-negative pathogens possess virulence-related type III secretion systems. Salmonella enterica uses two of these systems, encoded on the pathogenicity islands SPI-1 and SPI-2, respectively, to translocate more than 30 effector proteins into eukaryotic host cells. SteA is one of the few effectors that can be translocated by both systems. We investigated the conditions affecting the synthesis of this effector, its secretion to culture media and its translocation into host cells. Whereas steA was expressed under a wide range of conditions, some factors, including low and high osmolarity, and presence of butyrate, decreased expression. SteA was efficiently secreted to the culture media under both SPI-1 and SPI-2 inducing conditions. The kinetics of translocation into murine macrophages and human epithelial cells was studied using fusions with the 3xFLAG tag, and fusions with CyaA from Bordetella pertussis. Translocation into macrophages under non-invasive conditions was mainly dependent on the SPI-2-encoded type III secretion system but some participation of the SPI-1 system was also detected 6 hours post-infection. Interestingly, both type III secretion systems had a relevant role in the translocation of SteA into epithelial cells. Finally, a deletion approach allowed the identification of the N-terminal signal necessary for translocation of this effector. The amino acid residues 1-10 were sufficient to direct translocation into host cells through both type III secretion systems. Our results provide new examples of functional overlapping between the two type III secretion systems of Salmonella. PMID- 22046415 TI - Antibodies recognizing Mycobacterium avium paratuberculosis epitopes cross-react with the beta-cell antigen ZnT8 in Sardinian type 1 diabetic patients. AB - The environmental factors at play in the pathogenesis of type 1 diabetes (T1D) remain enigmatic. Mycobacterium avium subspecies paratuberculosis (MAP) is transmitted from dairy herds to humans through food contamination. MAP causes an asymptomatic infection that is highly prevalent in Sardinian T1D patients compared with type 2 diabetes (T2D) and healthy controls. Moreover, MAP elicits humoral responses against several mycobacterial proteins. We asked whether antibodies (Abs) against one of these proteins, namely MAP3865c, which displays a sequence homology with the beta-cell protein zinc transporter 8 (ZnT8) could be cross-reactive with ZnT8 epitopes. To this end, Ab responses against MAP3865c were analyzed in Sardinian T1D, T2D and healthy subjects using an enzymatic immunoassay. Abs against MAP3865c recognized two immunodominant transmembrane epitopes in 52-65% of T1D patients, but only in 5-7% of T2D and 3-5% of healthy controls. There was a linear correlation between titers of anti-MAP3865c and anti ZnT8 Abs targeting these two homologous epitopes, and pre-incubation of sera with ZnT8 epitope peptides blocked binding to the corresponding MAP3865c peptides. These results demonstrate that Abs recognizing MAP3865c epitopes cross-react with ZnT8, possibly underlying a molecular mimicry mechanism, which may precipitate T1D in MAP-infected individuals. PMID- 22046416 TI - Epilepsy caused by an abnormal alternative splicing with dosage effect of the SV2A gene in a chicken model. AB - Photosensitive reflex epilepsy is caused by the combination of an individual's enhanced sensitivity with relevant light stimuli, such as stroboscopic lights or video games. This is the most common reflex epilepsy in humans; it is characterized by the photoparoxysmal response, which is an abnormal electroencephalographic reaction, and seizures triggered by intermittent light stimulation. Here, by using genetic mapping, sequencing and functional analyses, we report that a mutation in the acceptor site of the second intron of SV2A (the gene encoding synaptic vesicle glycoprotein 2A) is causing photosensitive reflex epilepsy in a unique vertebrate model, the Fepi chicken strain, a spontaneous model where the neurological disorder is inherited as an autosomal recessive mutation. This mutation causes an aberrant splicing event and significantly reduces the level of SV2A mRNA in homozygous carriers. Levetiracetam, a second generation antiepileptic drug, is known to bind SV2A, and SV2A knock-out mice develop seizures soon after birth and usually die within three weeks. The Fepi chicken survives to adulthood and responds to levetiracetam, suggesting that the low-level expression of SV2A in these animals is sufficient to allow survival, but does not protect against seizures. Thus, the Fepi chicken model shows that the role of the SV2A pathway in the brain is conserved between birds and mammals, in spite of a large phylogenetic distance. The Fepi model appears particularly useful for further studies of physiopathology of reflex epilepsy, in comparison with induced models of epilepsy in rodents. Consequently, SV2A is a very attractive candidate gene for analysis in the context of both mono- and polygenic generalized epilepsies in humans. PMID- 22046417 TI - Transmission dynamics of low pathogenicity avian influenza infections in Turkey flocks. AB - Low pathogenicity avian influenza (LPAI) viruses of H5 and H7 subtypes have the potential to mutate into highly pathogenic strains (HPAI), which can threaten human health and cause huge economic losses. The current knowledge on the mechanisms of mutation from LPAI to HPAI is insufficient for predicting which H5 or H7 strains will mutate into an HPAI strain, and since the molecular changes necessary for the change in virulence seemingly occur at random, the probability of mutation depends on the number of virus replicates, which is associated with the number of birds that acquire infection. We estimated the transmission dynamics of LPAI viruses in turkeys using serosurveillance data from past epidemics in Italy. We fitted the proportions of birds infected in 36 flocks into a hierarchical model to estimate the basic reproduction number (R(0)) and possible variations in R(0) among flocks caused by differences among farms. We also estimated the distributions of the latent and infectious periods, using experimental infection data with outbreak strains. These were then combined with the R(0) to simulate LPAI outbreaks and characterise the resulting dynamics. The estimated mean within-flock R(0) in the population of infected flocks was 5.5, indicating that an infectious bird would infect an average of more than five susceptible birds. The results also indicate that the presence of seropositive birds does not necessarily mean that the virus has already been cleared and the flock is no longer infective, so that seropositive flocks may still constitute a risk of infection for other flocks. In light of these results, the enforcement of appropriate restrictions, the culling of seropositive flocks, or pre-emptive slaughtering may be useful. The model and parameter estimates presented in this paper provide the first complete picture of LPAI dynamics in turkey flocks and could be used for designing a suitable surveillance program. PMID- 22046418 TI - Atomic-level characterization of the activation mechanism of SERCA by calcium. AB - We have performed molecular dynamics (MD) simulations to elucidate, in atomic detail, the mechanism by which the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) is activated by Ca(2+). Crystal structures suggest that activation of SERCA occurs when the cytoplasmic head-piece, in an open (E1) conformation stabilized by Ca(2+), undergoes a large-scale open-to-closed (E1 to E2) transition that is induced by ATP binding. However, spectroscopic measurements in solution suggest that these structural states (E1 and E2) are not tightly coupled to biochemical states (defined by bound ligands); the closed E2 state predominates even in the absence of ATP, in both the presence and absence of Ca(2+). How is this loose coupling consistent with the high efficiency of energy transduction in the Ca(2+) ATPase? To provide insight into this question, we performed long (500 ns) all atom MD simulations starting from the open crystal structure, including a lipid bilayer and water. In both the presence and absence of Ca(2+), we observed a large-scale open-to-closed conformational transition within 400 ns, supporting the weak coupling between structural and biochemical states. However, upon closer inspection, it is clear that Ca(2+) is necessary and sufficient for SERCA to reach the precise geometrical arrangement necessary for activation of ATP hydrolysis. Contrary to suggestions from crystal structures, but in agreement with solution spectroscopy, the presence of ATP is not required for this activating transition. Principal component analysis showed that Ca(2+) reshapes the free energy landscape of SERCA to create a path between the open conformation and the activated closed conformation. Thus the malleability of the free energy landscape is essential for SERCA efficiency, ensuring that ATP hydrolysis is tightly coupled to Ca(2+) transport. These results demonstrate the importance of real-time dynamics in the formation of catalytically competent conformations of SERCA, with broad implications for understanding enzymatic catalysis in atomic detail. PMID- 22046419 TI - Is fetal growth restriction associated with a more severe maternal phenotype in the setting of early onset pre-eclampsia? A retrospective study. AB - BACKGROUND: Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. METHODS AND FINDINGS: We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005-2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). CONCLUSIONS: The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population. PMID- 22046420 TI - Functional correlations of pathogenesis-driven gene expression signatures in tuberculosis. AB - Tuberculosis remains a major health threat and its control depends on improved measures of prevention, diagnosis and treatment. Biosignatures can play a significant role in the development of novel intervention measures against TB and blood transcriptional profiling is increasingly exploited for their rational design. Such profiles also reveal fundamental biological mechanisms associated with the pathology of the disease. We have compared whole blood gene expression in TB patients, as well as in healthy infected and uninfected individuals in a cohort in The Gambia, West Africa and validated previously identified signatures showing high similarities of expression profiles among different cohorts. In this study, we applied a unique combination of classical gene expression analysis with pathway and functional association analysis integrated with intra-individual expression correlations. These analyses were employed for identification of new disease-associated gene signatures, identifying a network of Fc gamma receptor 1 signaling with correlating transcriptional activity as hallmark of gene expression in TB. Remarkable similarities to characteristic signatures in the autoimmune disease systemic lupus erythematosus (SLE) were observed. Functional gene clusters of immunoregulatory interactions involving the JAK-STAT pathway; sensing of microbial patterns by Toll-like receptors and IFN-signaling provide detailed insights into the dysregulation of critical immune processes in TB, involving active expression of both pro-inflammatory and immunoregulatory systems. We conclude that transcriptomics (i) provides a robust system for identification and validation of biosignatures for TB and (ii) application of integrated analysis tools yields novel insights into functional networks underlying TB pathogenesis. PMID- 22046421 TI - A common genetic variant (97906C>A) of DAB2IP/AIP1 is associated with an increased risk and early onset of lung cancer in Chinese males. AB - DOC-2/DAB2 interactive protein (DAB2IP) is a novel identified tumor suppressor gene that inhibits cell growth and facilitates cell apoptosis. One genetic variant in DAB2IP gene was reported to be associated with an increased risk of aggressive prostate cancer recently. Since DAB2IP involves in the development of lung cancer and low expression of DAB2IP are observed in lung cancer, we hypothesized that the variations in DAB2IP gene can increase the genetic susceptibility to lung cancer. In a case-control study of 1056 lung cancer cases and 1056 sex and age frequency-matched cancer-free controls, we investigated the association between two common polymorphisms in DAB2IP gene (-1420T>G, rs7042542; 97906C>A, rs1571801) and the risk of lung cancer. We found that compared with the 97906CC genotypes, carriers of variant genotypes (97906AC+AA) had a significant increased risk of lung cancer (adjusted odds ratio [OR] = 1.33, 95%CI = 1.04 1.70, P = 0.023) and the number of variant (risk) allele worked in a dose response manner (P(trend) = 0.0158). Further stratification analysis showed that the risk association was more pronounced in subjects aged less than 60 years old, males, non-smokers, non-drinkers, overweight groups and in those with family cancer history in first or second-degree relatives, and the 97906A interacted with overweight on lung cancer risk. We further found the number of risk alleles (97906A allele) were negatively correlated with early diagnosis age of lung cancer in male patients (P = 0.003). However, no significant association was observed on the -1420T>G polymorphism. Our data suggested that the 97906A variant genotypes are associated with the increased risk and early onset of lung cancer, particularly in males. PMID- 22046422 TI - How frontoparietal brain regions mediate imitative and complementary actions: an FMRI study. AB - The 'mirror neuron system' (MNS), located within inferior parietal lobe (IPL) and inferior frontal gyrus (IFG), creates an internal motor representation of the actions we see and has been implicated in imitation. Recently, the MNS has been implicated in non-identical responses: when the actions we must execute do not match those that we observe. However, in such conflicting situations non action specific cognitive control networks also located in frontoparietal regions may be involved. In the present functional magnetic resonance imaging (fMRI) study participants made both similar and dissimilar actions within two action contexts: imitative and complementary. We aimed to determine whether activity within IPL/IFG depends on (i) responding under an imitative versus complementary context (ii) responding with similar versus dissimilar responses, and (iii) observing hand actions versus symbolic arrow cue stimuli. Activity within rIPL/rIFG regions was largest during observation of hand actions compared with arrow cues. Specifically, rIPL/rIFG were recruited only during the imitative context, when participants responded with similar actions. When responding to symbolic arrow cues, rIPL/rIFG activity increased during dissimilar responses, reflecting increased demands placed on general cognitive control mechanisms. These results suggest a specific role of rIPL/rIFG during imitation of hand actions, and also a general role of frontoparietal areas in mediating dissimilar responses to both hand actions and symbolic stimuli. We discuss our findings in relation to recent work that has examined the role of frontoparietal brain structures in joint actions and inter-actor cooperation. We conclude that the specific brain regions identified here to show increased activation during action observation conditions are likely to form part of a mechanism specifically involved in matching observed actions directly with internal motor plans. Conversely, observation of arrow cues recruited part of a wider cognitive control network involved in the rapid remapping of stimulus-response associations. PMID- 22046423 TI - Palmitate-activated macrophages confer insulin resistance to muscle cells by a mechanism involving protein kinase C theta and epsilon. AB - BACKGROUND: Macrophage-derived factors contribute to whole-body insulin resistance, partly by impinging on metabolically active tissues. As proof of principle for this interaction, conditioned medium from macrophages treated with palmitate (CM-PA) reduces insulin action and glucose uptake in muscle cells. However, the mechanism whereby CM-PA confers this negative response onto muscle cells remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: L6-GLUT4myc myoblasts were exposed for 24 h to palmitate-free conditioned medium from RAW 264.7 macrophages pre-treated with 0.5 mM palmitate for 6 h. This palmitate-free CM-PA, containing selective cytokines and chemokines, inhibited myoblast insulin-stimulated insulin receptor substrate 1 (IRS1) tyrosine phosphorylation, AS160 phosphorylation, GLUT4 translocation and glucose uptake. These effects were accompanied by a rise in c-Jun N-terminal kinase (JNK) activation, degradation of Inhibitor of kappaBalpha (IkappaBalpha), and elevated expression of proinflammatory cytokines in myoblasts. Notably, CM-PA caused IRS1 phosphorylation on Ser1101, and phosphorylation of novel PKCtheta and epsilon. Co-incubation of myoblasts with CM PA and the novel and conventional PKC inhibitor Go6983 (but not with the conventional PKC inhibitor Go6976) prevented PKCtheta and epsilon activation, JNK phosphorylation, restored IkappaBalpha mass and reduced proinflammatory cytokine production. Go6983 also restored insulin signalling and glucose uptake in myoblasts. Moreover, co-silencing both novel PKC theta and epsilon isoforms in myoblasts by RNA interference, but not their individual silencing, prevented the inflammatory response and restored insulin sensitivity to CM-PA-treated myoblasts. CONCLUSIONS/CLINICAL SIGNIFICANCE: The results suggest that the block in muscle insulin action caused by CM-PA is mediated by novel PKCtheta and PKCepsilon. This study re-establishes the participation of macrophages as a relay in the action of fatty acids on muscle cells, and further identifies PKCtheta and PKCepsilon as key elements in the inflammatory and insulin resistance responses of muscle cells to macrophage products. Furthermore, it portrays these PKC isoforms as potential targets for the treatment of fatty acid-induced, inflammation-linked insulin resistance. PMID- 22046424 TI - Quantitative bias in Illumina TruSeq and a novel post amplification barcoding strategy for multiplexed DNA and small RNA deep sequencing. AB - Here we demonstrate a method for unbiased multiplexed deep sequencing of RNA and DNA libraries using a novel, efficient and adaptable barcoding strategy called Post Amplification Ligation-Mediated (PALM). PALM barcoding is performed as the very last step of library preparation, eliminating a potential barcode-induced bias and allowing the flexibility to synthesize as many barcodes as needed. We sequenced PALM barcoded micro RNA (miRNA) and DNA reference samples and evaluated the quantitative barcode-induced bias in comparison to the same reference samples prepared using the Illumina TruSeq barcoding strategy. The Illumina TruSeq small RNA strategy introduces the barcode during the PCR step using differentially barcoded primers, while the TruSeq DNA strategy introduces the barcode before the PCR step by ligation of differentially barcoded adaptors. Results show virtually no bias between the differentially barcoded miRNA and DNA samples, both for the PALM and the TruSeq sample preparation methods. We also multiplexed miRNA reference samples using a pre-PCR barcode ligation. This barcoding strategy results in significant bias. PMID- 22046425 TI - Postoperative adverse outcomes in intellectually disabled surgical patients: a nationwide population-based study. AB - BACKGROUND: Intellectually disabled patients have various comorbidities, but their risks of adverse surgical outcomes have not been examined. This study assesses pre-existing comorbidities, adjusted risks of postoperative major morbidities and mortality in intellectually disabled surgical patients. METHODS: A nationwide population-based study was conducted in patients who underwent inpatient major surgery in Taiwan between 2004 and 2007. Four controls for each patient were randomly selected from the National Health Insurance Research Database. Preoperative major comorbidities, postoperative major complications and 30-day in-hospital mortality were compared between patients with and without intellectual disability. Use of medical services also was analyzed. Adjusted odds ratios using multivariate logistic regression analyses with 95% confidence intervals were applied to verify intellectual disability's impact. RESULTS: Controls were compared with 3983 surgical patients with intellectual disability. Risks for postoperative major complications were increased in patients with intellectual disability, including acute renal failure (odds ratio 3.81, 95% confidence interval 2.28 to 6.37), pneumonia (odds ratio 2.01, 1.61 to 2.49), postoperative bleeding (odds ratio 1.35, 1.09 to 1.68) and septicemia (odds ratio 2.43, 1.85 to 3.21) without significant differences in overall mortality. Disability severity was positively correlated with postoperative septicemia risk. Medical service use was also significantly higher in surgical patients with intellectual disability. CONCLUSION: Intellectual disability significantly increases the risk of overall major complications after major surgery. Our findings show a need for integrated and revised protocols for postoperative management to improve care for intellectually disabled surgical patients. PMID- 22046427 TI - Altering host resistance to infections through microbial transplantation. AB - Host resistance to bacterial infections is thought to be dictated by host genetic factors. Infections by the natural murine enteric pathogen Citrobacter rodentium (used as a model of human enteropathogenic and enterohaemorrhagic E. coli infections) vary between mice strains, from mild self-resolving colonization in NIH Swiss mice to lethality in C3H/HeJ mice. However, no clear genetic component had been shown to be responsible for the differences observed with C. rodentium infections. Because the intestinal microbiota is important in regulating resistance to infection, and microbial composition is dependent on host genotype, it was tested whether variations in microbial composition between mouse strains contributed to differences in "host" susceptibility by transferring the microbiota of resistant mice to lethally susceptible mice prior to infection. Successful transfer of the microbiota from resistant to susceptible mice resulted in delayed pathogen colonization and mortality. Delayed mortality was associated with increased IL-22 mediated innate defense including antimicrobial peptides Reg3gamma and Reg3beta, and immunono-neutralization of IL-22 abrogated the beneficial effect of microbiota transfer. Conversely, depletion of the native microbiota in resistant mice by antibiotics and transfer of the susceptible mouse microbiota resulted in reduced innate defenses and greater pathology upon infection. This work demonstrates the importance of the microbiota and how it regulates mucosal immunity, providing an important factor in susceptibility to enteric infection. Transfer of resistance through microbial transplantation (bacteriotherapy) provides additional mechanisms to alter "host" resistance, and a novel means to alter enteric infection and to study host-pathogen interactions. PMID- 22046428 TI - Genetic ablation of PLA2G6 in mice leads to cerebellar atrophy characterized by Purkinje cell loss and glial cell activation. AB - Infantile neuroaxonal dystrophy (INAD) is a progressive, autosomal recessive neurodegenerative disease characterized by axonal dystrophy, abnormal iron deposition and cerebellar atrophy. This disease was recently mapped to PLA2G6, which encodes group VI Ca(2+)-independent phospholipase A(2) (iPLA(2) or iPLA(2)beta). Here we show that genetic ablation of PLA2G6 in mice (iPLA(2)beta( /-)) leads to the development of cerebellar atrophy by the age of 13 months. Atrophied cerebella exhibited significant loss of Purkinje cells, as well as reactive astrogliosis, the activation of microglial cells, and the pronounced up regulation of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF alpha) and interleukin-1beta (IL-1beta). Moreover, glial cell activation and the elevation in TNF-alpha and IL-1beta expression occurred before apparent cerebellar atrophy. Our findings indicate that the absence of PLA2G6 causes neuroinflammation and Purkinje cell loss and ultimately leads to cerebellar atrophy. Our study suggests that iPLA(2)beta(-/-) mice are a valuable model for cerebellar atrophy in INAD and that early anti-inflammatory therapy may help slow the progression of cerebellar atrophy in this deadly neurodegenerative disease. PMID- 22046429 TI - Urocortin-1 within the centrally-projecting Edinger-Westphal nucleus is critical for ethanol preference. AB - Converging lines of evidence point to the involvement of neurons of the centrally projecting Edinger-Westphal nucleus (EWcp) containing the neuropeptide Urocortin 1 (Ucn1) in excessive ethanol (EtOH) intake and EtOH sensitivity. Here, we expanded these previous findings by using a continuous-access, two-bottle choice drinking paradigm (3%, 6%, and 10% EtOH vs. tap water) to compare EtOH intake and EtOH preference in Ucn1 genetic knockout (KO) and wild-type (WT) mice. Based on previous studies demonstrating that electrolytic lesion of the EWcp attenuated EtOH intake and preference in high-drinking C57BL/6J mice, we also set out to determine whether EWcp lesion would differentially alter EtOH consumption in Ucn1 KO and WT mice. Finally, we implemented well-established place conditioning procedures in KO and WT mice to determine whether Ucn1 and the corticotropin releasing factor type-2 receptor (CRF-R2) were involved in the rewarding and aversive effects of EtOH (2 g/kg, i.p.). Results from these studies revealed that (1) genetic deletion of Ucn1 dampened EtOH preference only in mice with an intact EWcp, but not in mice that received lesion of the EWcp, (2) lesion of the EWcp dampened EtOH intake in Ucn1 KO and WT mice, but dampened EtOH preference only in WT mice expressing Ucn1, and (3) genetic deletion of Ucn1 or CRF-R2 abolished the conditioned rewarding effects of EtOH, but deletion of Ucn1 had no effect on the conditioned aversive effects of EtOH. The current findings provide strong support for the hypothesis that EWcp-Ucn1 neurons play an important role in EtOH intake, preference, and reward. PMID- 22046426 TI - Structural basis for broad neutralization of hepatitis C virus quasispecies. AB - Monoclonal antibodies directed against hepatitis C virus (HCV) E2 protein can neutralize cell-cultured HCV and pseudoparticles expressing envelopes derived from multiple HCV subtypes. For example, based on antibody blocking experiments and alanine scanning mutagenesis, it was proposed that the AR3B monoclonal antibody recognized a discontinuous conformational epitope comprised of amino acid residues 396-424, 436-447, and 523-540 of HCV E2 envelope protein. Intriguingly, one of these segments (436-447) overlapped with hypervariable region 3 (HVR3), a domain that exhibited significant intrahost and interhost genetic diversity. To reconcile these observations, amino-acid sequence variability was examined and homology-based structural modelling of E2 based on tick-borne encephalitis virus (TBEV) E protein was performed based on 413 HCV sequences derived from 18 subjects with chronic hepatitis C. Here we report that despite a high degree of amino-acid sequence variability, the three-dimensional structure of E2 is remarkably conserved, suggesting broad recognition of structural determinants rather than specific residues. Regions 396-424 and 523 540 were largely exposed and in close spatial proximity at the surface of E2. In contrast, region 436-447, which overlaps with HVR3, was >35 A away, and estimates of buried surface were inconsistent with HVR3 being part of the AR3B binding interface. High-throughput structural analysis of HCV quasispecies could facilitate the development of novel vaccines that target conserved structural features of HCV envelope and elicit neutralizing antibody responses that are less vulnerable to viral escape. PMID- 22046430 TI - RNA-Seq reveals an integrated immune response in nucleated erythrocytes. AB - BACKGROUND: Throughout the primary literature and within textbooks, the erythrocyte has been tacitly accepted to have maintained a unique physiological role; namely gas transport and exchange. In non-mammalian vertebrates, nucleated erythrocytes are present in circulation throughout the life cycle and a fragmented series of observations in mammals support a potential role in non respiratory biological processes. We hypothesised that nucleated erythrocytes could actively participate via ligand-induced transcriptional re-programming in the immune response. METHODOLOGY/PRINCIPAL FINDINGS: Nucleated erythrocytes from both fish and birds express and regulate specific pattern recognition receptor (PRR) mRNAs and, thus, are capable of specific pathogen associated molecular pattern (PAMP) detection that is central to the innate immune response. In vitro challenge with diverse PAMPs led to de novo specific mRNA synthesis of both receptors and response factors including interferon-alpha (IFNalpha) that exhibit a stimulus-specific polysomal shift supporting active translation. RNA-Seq analysis of the PAMP (Poly (I:C), polyinosinic:polycytidylic acid)-erythrocyte response uncovered diverse cohorts of differentially expressed mRNA transcripts related to multiple physiological systems including the endocrine, reproductive and immune. Moreover, erythrocyte-derived conditioned mediums induced a type-1 interferon response in macrophages thus supporting an integrative role for the erythrocytes in the immune response. CONCLUSIONS/SIGNIFICANCE: We demonstrate that nucleated erythrocytes in non-mammalian vertebrates spanning significant phylogenetic distance participate in the immune response. RNA-Seq studies highlight a mRNA repertoire that suggests a previously unrecognized integrative role for the erythrocytes in other physiological systems. PMID- 22046431 TI - Evolutionary history of the vertebrate mitogen activated protein kinases family. AB - BACKGROUND: The mitogen activated protein kinases (MAPK) family pathway is implicated in diverse cellular processes and pathways essential to most organisms. Its evolution is conserved throughout the eukaryotic kingdoms. However, the detailed evolutionary history of the vertebrate MAPK family is largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: The MAPK family members were collected from literatures or by searching the genomes of several vertebrates and invertebrates with the known MAPK sequences as queries. We found that vertebrates had significantly more MAPK family members than invertebrates, and the vertebrate MAPK family originated from 3 progenitors, suggesting that a burst of gene duplication events had occurred after the divergence of vertebrates from invertebrates. Conservation of evolutionary synteny was observed in the vertebrate MAPK subfamilies 4, 6, 7, and 11 to 14. Based on synteny and phylogenetic relationships, MAPK12 appeared to have arisen from a tandem duplication of MAPK11 and the MAPK13-MAPK14 gene unit was from a segmental duplication of the MAPK11-MAPK12 gene unit. Adaptive evolution analyses reveal that purifying selection drove the evolution of MAPK family, implying strong functional constraints of MAPK genes. Intriguingly, however, intron losses were specifically observed in the MAPK4 and MAPK7 genes, but not in their flanking genes, during the evolution from teleosts to amphibians and mammals. The specific occurrence of intron losses in the MAPK4 and MAPK7 subfamilies might be associated with adaptive evolution of the vertebrates by enhancing the gene expression level of both MAPK genes. CONCLUSIONS/SIGNIFICANCE: These results provide valuable insight into the evolutionary history of the vertebrate MAPK family. PMID- 22046432 TI - Dissolution of pre-existing platelet thrombus by synergistic administration of low concentrations of bifunctional antibodies against beta3 integrin. AB - Most antithrombotic approaches target prevention rather than the more clinically relevant issue of resolution of an existing thrombus. In this study, we describe a novel and effective therapeutic strategy for ex vivo clearance of pre-existing platelet thrombus by the combination of two bifunctional platelet GPIIIa49-66 ligands that target different parts of the arterial thrombus. We produced an additional GPIIIa49-66 agent (named APAC), which homes to activated platelets. Like our previously described SLK (which targets newly deposited fibrin strands surrounding the platelet thrombus), APAC destroys platelet aggregates ex vivo in an identical fashion with 85% destruction of platelet aggregates at 2 hours. The combined application of APAC and SLK demonstrated a ~2 fold greater platelet thrombus dissolution than either agent alone at a low concentration (0.025 uM). Platelet-rich clot lysis experiments demonstrated the time required for 50% platelet-rich fibrin clot lysis (T(50%)) by APAC (95 +/- 6.1 min) or SLK (145 +/- 7.1 min) was much longer than that by combined APAC + SLK (65 +/- 7.6 min) at the final concentration of 0.025 uM (APAC + SLK vs APAC, p<0.05; APAC + SLK vs SLK, p<0.01). Thus these low concentrations of a combination of both agents are likely to be more effective and less toxic when used therapeutically in vivo. PMID- 22046433 TI - Deletion of exon 20 of the Familial Dysautonomia gene Ikbkap in mice causes developmental delay, cardiovascular defects, and early embryonic lethality. AB - Familial Dysautonomia (FD) is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, and leads to death before the age of 40. The disease is characterized by abnormal development and progressive degeneration of the sensory and autonomic nervous system. A single base pair substitution in intron 20 of the Ikbkap gene accounts for 98% of FD cases, and results in the expression of low levels of the full-length mRNA with simultaneous expression of an aberrantly spliced mRNA in which exon 20 is missing. To date, there is no animal model for the disease, and the essential cellular functions of IKAP--the protein encoded by Ikbkap--remain unknown. To better understand the normal function of IKAP and in an effort to generate a mouse model for FD, we have targeted the mouse Ikbkap gene by homologous recombination. We created two distinct alleles that result in either loss of Ikbkap expression, or expression of an mRNA lacking only exon 20. Homozygosity for either mutation leads to developmental delay, cardiovascular and brain malformations, accompanied with early embryonic lethality. Our analyses indicate that IKAP is essential for expression of specific genes involved in cardiac morphogenesis, and that cardiac failure is the likely cause of abnormal vascular development and embryonic lethality. Our results also indicate that deletion of exon 20 abolishes gene function. This implies that the truncated IKAP protein expressed in FD patients does not retain any significant biological function. PMID- 22046434 TI - Overexpression of a minimal domain of calpastatin suppresses IL-6 production and Th17 development via reduced NF-kappaB and increased STAT5 signals. AB - Calpain, a calcium-dependent cysteine protease, is reportedly involved in the pathophysiology of autoimmune diseases such as rheumatoid arthritis (RA). In addition, autoantibodies against calpastatin, a natural and specific inhibitor of calpain, are widely observed in RA. We previously reported that E-64-d, a membrane-permeable cysteine protease inhibitor, is effective in treating experimental arthritis. However, the exact role of the calpastatin-calpain balance in primary inflammatory cells remains unclear. Here we investigated the effect of calpain-specific inhibition by overexpressing a minimal functional domain of calpastatin in primary helper T (Th) cells, primary fibroblasts from RA patients, and fibroblast cell lines. We found that the calpastatin-calpain balance varied during Th1, Th2, and Th17 development, and that overexpression of a minimal domain of calpastatin (by retroviral gene transduction) or the inhibition of calpain by E-64-d suppressed the production of IL-6 and IL-17 by Th cells and the production of IL-6 by fibroblasts. These suppressions were associated with reductions in RORgammat expression and STAT3 phosphorylation. Furthermore, inhibiting calpain by silencing its small regulatory subunit (CPNS) suppressed Th17 development. We also confirmed that overexpressing a minimal domain of calpastatin suppressed IL-6 by reducing NF-kappaB signaling via the stabilization of IkappaBalpha, without affecting the upstream signal. Moreover, our findings indicated that calpastatin overexpression suppressed IL-17 production by Th cells by up-regulating the STAT5 signal. Finally, overexpression of a minimal domain of calpastatin suppressed IL-6 production efficiently in primary fibroblasts derived from the RA synovium. These findings suggest that inhibiting calpain by overexpressing a minimal domain of calpastatin could coordinately suppress proinflammatory activities, not only those of Th cells but also of synovial fibroblasts. Thus, this strategy may prove viable as a candidate treatment for inflammatory diseases such as RA. PMID- 22046435 TI - Deep sequencing the transcriptome reveals seasonal adaptive mechanisms in a hibernating mammal. AB - Mammalian hibernation is a complex phenotype involving metabolic rate reduction, bradycardia, profound hypothermia, and a reliance on stored fat that allows the animal to survive for months without food in a state of suspended animation. To determine the genes responsible for this phenotype in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) we used the Roche 454 platform to sequence mRNA isolated at six points throughout the year from three key tissues: heart, skeletal muscle, and white adipose tissue (WAT). Deep sequencing generated approximately 3.7 million cDNA reads from 18 samples (6 time points *3 tissues) with a mean read length of 335 bases. Of these, 3,125,337 reads were assembled into 140,703 contigs. Approximately 90% of all sequences were matched to proteins in the human UniProt database. The total number of distinct human proteins matched by ground squirrel transcripts was 13,637 for heart, 12,496 for skeletal muscle, and 14,351 for WAT. Extensive mitochondrial RNA sequences enabled a novel approach of using the transcriptome to construct the complete mitochondrial genome for I. tridecemlineatus. Seasonal and activity-specific changes in mRNA levels that met our stringent false discovery rate cutoff (1.0 * 10(-11)) were used to identify patterns of gene expression involving various aspects of the hibernation phenotype. Among these patterns are differentially expressed genes encoding heart proteins AT1A1, NAC1 and RYR2 controlling ion transport required for contraction and relaxation at low body temperatures. Abundant RNAs in skeletal muscle coding ubiquitin pathway proteins ASB2, UBC and DDB1 peak in October, suggesting an increase in muscle proteolysis. Finally, genes in WAT that encode proteins involved in lipogenesis (ACOD, FABP4) are highly expressed in August, but gradually decline in expression during the seasonal transition to lipolysis. PMID- 22046436 TI - Categorization of extremely brief auditory stimuli: domain-specific or domain general processes? AB - The present study investigated the minimum amount of auditory stimulation that allows differentiation of spoken voices, instrumental music, and environmental sounds. Three new findings were reported. 1) All stimuli were categorized above chance level with 50 ms-segments. 2) When a peak-level normalization was applied, music and voices started to be accurately categorized with 20 ms-segments. When the root-mean-square (RMS) energy of the stimuli was equalized, voice stimuli were better recognized than music and environmental sounds. 3) Further psychoacoustical analyses suggest that the categorization of extremely brief auditory stimuli depends on the variability of their spectral envelope in the used set. These last two findings challenge the interpretation of the voice superiority effect reported in previously published studies and propose a more parsimonious interpretation in terms of an emerging property of auditory categorization processes. PMID- 22046437 TI - CARM1 mediates modulation of Sox2. AB - Sox2 is a key component of the transcription factor network that maintains the pluripotent state of embryonic stem cells (ESCs). Sox2 is regulated by multiple post-translational modifications, including ubiquitination, sumoylation, acetylation and phosphorylation. Here we report that Sox2 is in association with and methylated by coactivator-associated arginine methyltransferase 1 (CARM1), a protein arginine methyltransferase that plays a pivotal role in ESCs. We found that CARM1 facilitates Sox2-mediated transactivation and directly methylates Sox2 at arginine 113. This methylation event enhances Sox2 self-association. Furthermore, the physiological retention of Sox2 on chromatin restricts the Sox2 methylation level. Our study reveals the direct regulation of Sox2 by CARM1 that sheds lights on how arginine methylation signals are integrated into the pluripotent transcription factor network. PMID- 22046438 TI - Bacterial-epithelial contact is a key determinant of host innate immune responses to enteropathogenic and enteroaggregative Escherichia coli. AB - BACKGROUND: Enteropathogenic (EPEC) and Enteroaggregative (EAEC) E. coli have similar, but distinct clinical symptoms and modes of pathogenesis. Nevertheless when they infect the gastrointestinal tract, it is thought that their flagellin causes IL-8 release leading to neutrophil recruitment and gastroenteritis. However, this may not be the whole story as the effect of bacterial adherence to IEC innate response(s) remains unclear. Therefore, we have characterized which bacterial motifs contribute to the innate epithelial response to EPEC and EAEC, using a range of EPEC and EAEC isogenic mutant strains. METHODOLOGY: Caco-2 and HEp-2 cell lines were exposed to prototypical EPEC strain E2348/69 or EAEC strain O42, in addition to a range of isogenic mutant strains. E69 [LPS, non-motile, non adherent, type three secretion system (TTSS) negative, signalling negative] or O42 [non-motile, non-adherent]. IL-8 and CCL20 protein secretion was measured. Bacterial surface structures were assessed by negative staining Transmission Electron Microscopy. The Fluorescent-actin staining test was carried out to determine bacterial adherence. RESULTS: Previous studies have reported a balance between the host pro-inflammatory response and microbial suppression of this response. In our system an overall balance towards the host pro-inflammatory response is seen with the E69 WT and to a greater extent O42 WT, which is in fit with clinical symptoms. On removal of the external EPEC structures flagella, LPS, BFP, EspA and EspC; and EAEC flagella and AAF, the host inflammatory response is reduced. However, removal of E69 lymphostatin increases the host inflammatory response suggesting involvement in the bacterial mediated anti-inflammatory response. CONCLUSION: Epithelial responses were due to combinations of bacterial agonists, with host-bacterial contact a key determinant of these innate responses. Host epithelial recognition was offset by the microbe's ability to down-regulate the inflammatory response. Understanding the complexity of this host-microbial balance will contribute to improved vaccine design for infectious gastroenteritis. PMID- 22046439 TI - Serum A-FABP is increased and closely associated with elevated NT-proBNP levels in type 2 diabetic patients treated with rosiglitazone. AB - BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) has been shown to play important roles in the development of metabolic syndrome, diabetes, and cardiovascular diseases. In this study we investigated the possible role of A FABP in the development of cardiac dysfunction related to rosiglitazone treatment. METHODOLOGY/PRINCIPAL FINDINGS: A total of 84 patients with newly diagnosed type 2 diabetes were treated with rosiglitazone for 48 weeks. Circulating A-FABP and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined at baseline and repeated at 24 and 48 weeks. After the 48 week rosiglitazone treatment period, serum levels of both A-FABP and NT-proBNP increased progressively and significantly (P<0.01). Serum levels of A-FABP were demonstrated to be positively correlated with gender and waist circumference both at baseline and the end of the study, and with age, body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and NT-proBNP at 48 weeks (all P<0.05). In addition, changes in A-FABP were significantly and positively correlated with changes in NT-proBNP (r = 0.239, P = 0.039). Furthermore, multiple stepwise regression analysis showed that the changes in A-FABP were independently and positively associated with changes in NT proBNP after adjusting for confounding factors (beta = 0.320, P = 0.007). CONCLUSIONS/SIGNIFICANCE: Rosiglitazone-mediated increase of A-FABP is closely associated with the elevation of NT-proBNP, a well-established marker of cardiac dysfunction. The findings of our study imply that A-FABP may mediate the cross talk between heart and adipose tissue. PMID- 22046440 TI - Acetylation of the pro-apoptotic factor, p53 in the hippocampus following cerebral ischemia and modulation by estrogen. AB - BACKGROUND: Recent studies demonstrate that acetylation of the transcription factor, p53 on lysine(373) leads to its enhanced stabilization/activity and increased susceptibility of cells to stress. However, it is not known whether acetylation of p53 is altered in the hippocampus following global cerebral ischemia (GCI) or is regulated by the hormone, 17beta-estradiol (17beta-E(2)), and thus, this study examined these issues. METHODOLOGY/PRINCIPAL FINDINGS: The study revealed that Acetyl p53-Lysine(373) levels were markedly increased in the hippocampal CA1 region after GCI at 3 h, 6 h and 24 h after reperfusion, an effect strongly attenuated by 17beta-E(2). 17beta-E(2) also enhanced interaction of p53 with the ubiquitin ligase, Mdm2, increased ubiquitination of p53, and induced its down-regulation, as well as attenuated elevation of the p53 transcriptional target, Puma. We also observed enhanced acetylation of p53 at a different lysine (Lys(382)) at 3 h after reperfusion, and 17beta-E(2) also markedly attenuated this effect. Furthermore, administration of an inhibitor of CBP/p300 acetyltransferase, which acetylates p53, was strongly neuroprotective of the CA1 region following GCI. In long-term estrogen deprived (LTED) animals, the ability of 17beta-E(2) to attenuate p53 acetylation was lost, and intriguingly, Acetyl p53-Lysine(373) levels were markedly elevated in sham (non-ischemic) LTED animals. Finally, intracerebroventricular injections of Gp91ds-Tat, a specific NADPH oxidase (NOX2) inhibitor, but not the scrambled tat peptide control (Sc Tat), attenuated acetylation of p53 and reduced levels of Puma following GCI. CONCLUSIONS/SIGNIFICANCE: The studies demonstrate that p53 undergoes enhanced acetylation in the hippocampal CA1 region following global cerebral ischemia, and that the neuroprotective agent, 17beta-E(2), markedly attenuates the ischemia induced p53 acetylation. Furthermore, following LTED, the suppressive effect of 17beta-E(2) on p53 acetylation is lost, and p53 acetylation increases in the hippocampus, which may explain previous reports of increased sensitivity of the hippocampus to ischemic stress following LTED. PMID- 22046441 TI - IFI16 protein mediates the anti-inflammatory actions of the type-I interferons through suppression of activation of caspase-1 by inflammasomes. AB - BACKGROUND: Type-I interferons (IFNs) are used to treat certain inflammatory diseases. Moreover, activation of type-I IFN-signaling in immune cells inhibits the production of proinflammatory cytokines and activation of inflammasomes. However, the molecular mechanisms remain largely unknown. Upon sensing cytosolic double-stranded DNA, the AIM2 protein forms the AIM2-ASC inflammasome, resulting in activation of caspase-1. Given that the IFI16 and AIM2 proteins are IFN inducible and can heterodimerize with each other, we investigated the regulation of IFI16, AIM2, and inflammasome proteins by type-I and type-II IFNs and explored whether the IFI16 protein could negatively regulate the activation of the AIM2 (or other) inflammasome. METHODOLOGY/ PRINCIPAL FINDINGS: We found that basal levels of the IFI16 and AIM2 proteins were relatively low in peripheral blood monocytes (CD14(+)) and in the THP-1 monocytic cell line. However, treatment of THP-1 cells with type-I (IFN-alpha or beta) or type-II (IFN-gamma) IFN induced the expression levels of IFI16, AIM2, ASC and CASP1 proteins. The induced levels of IFI16 and AIM2 proteins were detected primarily in the cytoplasm. Accordingly, relatively more IFI16 protein bound with the AIM2 protein in the cytoplasmic fraction. Notably, increased expression of IFI16 protein in transfected HEK-293 cells inhibited activation of caspase-1 by the AIM2-ASC inflammasome. Moreover, the constitutive knockdown of the IFI16 expression in THP-1 cells increased the basal and induced [induced by poly(dA:dT) or alum] activation of the caspase-1 by the AIM2 and NLRP3 inflammasomes. CONCLUSIONS/SIGNIFICANCE: Our observations revealed that the type-I and type-II IFNs induce the expression of IFI16, AIM2, and inflammasome proteins to various extents in THP-1 cells and the expression of IFI16 protein in THP-1 cells suppresses the activation of caspase-1 by the AIM2 and NLRP3 inflammasomes. Thus, our observations identify the IFI16 protein as a mediator of the anti-inflammatory actions of the type-I IFNs. PMID- 22046442 TI - Sensitization of glioma cells to tamoxifen-induced apoptosis by Pl3-kinase inhibitor through the GSK-3beta/beta-catenin signaling pathway. AB - Malignant gliomas represent one of the most aggressive types of cancers and their recurrence is closely linked to acquired therapeutic resistance. A combination of chemotherapy is considered a promising therapeutic model in overcoming therapeutic resistance and enhancing treatment efficacy. Herein, we show by colony formation, Hochest 33342 and TUNEL staining, as well as by flow cytometric analysis, that LY294002, a specific phosphatidylinositide-3-kinase (PI3K) inhibitor, enhanced significantly the sensitization of a traditional cytotoxic chemotherapeutic agent, tamoxifen-induced apoptosis in C6 glioma cells. Activation of PI3K signaling pathway by IGF-1 protected U251 cells from apoptosis induced by combination treatment of LY294002 and tamoxifen. Interference of PI3K signaling pathway by PI3K subunit P85 siRNA enhanced the sensitization of U251 glioma cells to tamoxifen -induced apoptosis. By Western blotting, we found that combination treatment showed lower levels of phosphorylated Akt(Ser473) and GSK 3beta(Ser9) than a single treatment of LY294002. Further, we showed a significant decrease of nuclear beta-catenin by combination treatment. In response to the inhibition of beta-catenin signaling, mRNA and protein levels of Survivin and the other three antiapoptotic genes Bcl-2, Bcl-xL, and Mcl-1 were significantly decreased by combination treatment. Our results indicated that the synergistic cytotoxic effect of LY294002 and tamoxifen is achieved by the inhibition of GSK 3beta/beta-catenin signaling pathway. PMID- 22046443 TI - Within- and across-species responses of plant traits and litter decomposition to elevation across contrasting vegetation types in subarctic tundra. AB - Elevational gradients are increasingly recognized as a valuable tool for understanding how community and ecosystem properties respond to climatic factors, but little is known about how plant traits and their effects on ecosystem processes respond to elevation. We studied the response of plant leaf and litter traits, and litter decomposability across a gradient of elevation, and thus temperature, in subarctic tundra in northern Sweden for each of two contrasting vegetation types, heath and meadow, dominated by dwarf shrubs and herbaceous plants respectively. This was done at each of three levels; across species, within individual species, and the plant community using a community weighted average approach. Several leaf and litter traits shifted with increasing elevation in a manner consistent with greater conservation of nutrients at all three levels, and the most consistent response was an increase in tissue N to P ratio. However, litter decomposition was less directly responsive to elevation because the leaf and litter traits which were most responsive to elevation were not necessarily those responsible for driving decomposition. At the community level, the response to elevation of foliar and litter traits, and decomposability, varied greatly among the two vegetation types, highlighting the importance of vegetation type in determining ecological responses to climatic factors such as temperature. Finally our results highlight how understanding the responses of leaf and litter characteristics of functionally distinct vegetation types, and the processes that they drive, to temperature helps provide insights about how future climate change could affect tundra ecosystems. PMID- 22046444 TI - Chronic fluid flow is an environmental modifier of renal epithelial function. AB - Although solitary or sensory cilia are present in most cells of the body and their existence has been known since the sixties, very little is been known about their functions. One suspected function is fluid flow sensing- physical bending of cilia produces an influx of Ca(++), which can then result in a variety of activated signaling pathways. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a progressive disease, typically appearing in the 5(th) decade of life and is one of the most common monogenetic inherited human diseases, affecting approximately 600,000 people in the United States. Because ADPKD is a slowly progressing disease, I asked how fluid flow may act, via the primary cilium, to alter epithelial physiology during the course of cell turnover. I performed an experiment to determine under what conditions fluid flow can result in a change of function of renal epithelial tissue. A wildtype epithelial cell line derived the cortical collecting duct of a heterozygous offspring of the Immortomouse (Charles River Laboratory) was selected as our model system. Gentle orbital shaking was used to induce physiologically relevant fluid flow, and periodic measurements of the transepithelial Sodium current were performed. At the conclusion of the experiment, mechanosensitive proteins of interest were visualized by immunostaining. I found that fluid flow, in itself, modifies the transepithelial sodium current, cell proliferation, and the actin cytoskeleton. These results significantly impact the understanding of both the mechanosensation function of primary cilia as well as the understanding of ADPKD disease progression. PMID- 22046445 TI - Cell-cell contact preserves cell viability via plakoglobin. AB - Control over cell viability is a fundamental property underlying numerous physiological processes. Cell spreading on a substrate was previously demonstrated to be a major factor in determining the viability of individual cells. In multicellular organisms, cell-cell contact is likely to play a significant role in regulating cell vitality, but its function is easily masked by cell-substrate interactions, thus remains incompletely characterized. In this study, we show that suspended immortalized human keratinocyte sheets with persisting intercellular contacts exhibited significant contraction, junctional actin localization, and reinforcement of cell-cell adhesion strength. Further, cells within these sheets remain viable, in contrast to trypsinized cells suspended without either cell-cell or cell-substrate contact, which underwent apoptosis at high rates. Suppression of plakoglobin weakened cell-cell adhesion in cell sheets and suppressed apoptosis in suspended, trypsinized cells. These results demonstrate that cell-cell contact may be a fundamental control mechanism governing cell viability and that the junctional protein plakoglobin is a key regulator of this process. Given the near-ubiquity of plakoglobin in multicellular organisms, these findings could have significant implications for understanding cell adhesion, modeling disease progression, developing therapeutics and improving the viability of tissue engineering protocols. PMID- 22046446 TI - Sedimentary environment influences the effect of an infaunal suspension feeding bivalve on estuarine ecosystem function. AB - The suspension feeding bivalve Austrovenus stutchburyi is a key species on intertidal sandflats in New Zealand, affecting the appearance and functioning of these systems, but is susceptible to several environmental stressors including sedimentation. Previous studies into the effect of this species on ecosystem function have been restricted in space and time, limiting our ability to infer the effect of habitat change on functioning. We examined the effect of Austrovenus on benthic primary production and nutrient dynamics at two sites, one sandy, the other composed of muddy-sand to determine whether sedimentary environment alters this key species' role. At each site we established large (16 m(2)) plots of two types, Austrovenus addition and removal. In winter and summer we deployed light and dark benthic chambers to quantify oxygen and nutrient fluxes and measured sediment denitrification enzyme activity to assess denitrification potential. Rates of gross primary production (GPP) and ammonium uptake were significantly increased when Austrovenus was added, relative to removed, at the sandy site (GPP, 1.5 times greater in winter and summer; ammonium uptake, 8 times greater in summer; 3-factor analysis of variance (ANOVA), p<0.05). Denitrification potential was also elevated in Austrovenus addition plots at the sandy site in summer (by 1.6 times, p<0.1). In contrast, there was no effect of Austrovenus treatment on any of these variables at the muddy-sand site, and overall rates tended to be lower at the muddy-sand site, relative to the sandy site (e.g. GPP was 2.1 to 3.4 times lower in winter and summer, respectively, p<0.001). Our results suggest that the positive effects of Austrovenus on system productivity and denitrification potential is limited at a muddy-sand site compared to a sandy site, and reveal the importance of considering sedimentary environment when examining the effect of key species on ecosystem function. PMID- 22046447 TI - The mitochondrial genome of Baylisascaris procyonis. AB - BACKGROUND: Baylisascaris procyonis (Nematoda: Ascaridida), an intestinal nematode of raccoons, is emerging as an important helminthic zoonosis due to serious or fatal larval migrans in animals and humans. Despite its significant veterinary and public health impact, the epidemiology, molecular ecology and population genetics of this parasite remain largely unexplored. Mitochondrial (mt) genomes can provide a foundation for investigations in these areas and assist in the diagnosis and control of B. procyonis. In this study, the first complete mt genome sequence of B. procyonis was determined using a polymerase chain reaction (PCR)-based primer-walking strategy. METHODOLOGY/PRINCIPAL FINDINGS: The circular mt genome (14781 bp) of B. procyonis contained 12 protein coding, 22 transfer RNA and 2 ribosomal RNA genes congruent with other chromadorean nematodes. Interestingly, the B. procyonis mtDNA featured an extremely long AT-rich region (1375 bp) and a high number of intergenic spacers (17), making it unique compared with other secernentean nematodes characterized to date. Additionally, the entire genome displayed notable levels of AT skew and GC skew. Based on pairwise comparisons and sliding window analysis of mt genes among the available 11 Ascaridida mtDNAs, new primer pairs were designed to amplify specific short fragments of the genes cytb (548 bp fragment) and rrnL (200 bp fragment) in the B. procyonis mtDNA, and tested as possible alternatives to existing mt molecular beacons for Ascaridida. Finally, phylogenetic analysis of mtDNAs provided novel estimates of the interrelationships of Baylisasaris and Ascaridida. CONCLUSIONS/SIGNIFICANCE: The complete mt genome sequence of B. procyonis sequenced here should contribute to molecular diagnostic methods, epidemiological investigations and ecological studies of B. procyonis and other related ascaridoids. The information will be important in refining the phylogenetic relationships within the order Ascaridida and enriching the resource of markers for systematic, population genetic and evolutionary biological studies of parasitic nematodes of socio-economic importance. PMID- 22046448 TI - Erythropoietin enhances nerve repair in anti-ganglioside antibody-mediated models of immune neuropathy. AB - Guillain-Barre syndrome (GBS) is a monophasic immune neuropathic disorder in which a significant proportion of patients have incomplete recovery. The patients with incomplete recovery almost always have some degree of failure of axon regeneration and target reinnervation. Anti-ganglioside antibodies (Abs) are the most commonly recognized autoimmune markers in all forms of GBS and specific Abs are associated with the slow/poor recovery. We recently demonstrated that specific anti-ganglioside Abs inhibit axonal regeneration and nerve repair in preclinical models by activation of small GTPase RhoA and its downstream effectors. The objective of this study was to determine whether erythropoietin (EPO), a pleiotropic cytokine with neuroprotective and neurotrophic properties, enhances nerve regeneration in preclinical cell culture and animal models of autoimmune neuropathy/nerve repair generated with monoclonal and patient derived Abs. Primary neuronal cultures and a standardized sciatic crush nerve model were used to assess the efficacy of EPO in reversing inhibitory effects of anti ganglioside Abs on nerve repair. We found that EPO completely reversed the inhibitory effects of anti-ganglioside Abs on axon regeneration in cell culture models and significantly improved nerve regeneration/repair in an animal model. Moreover, EPO-induced proregenerative effects in nerve cells are through EPO receptors and Janus kinase 2/Signal transducer and activator of transcription 5 pathway and not via early direct modulation of small GTPase RhoA. These preclinical studies indicate that EPO is a viable candidate drug to develop further for neuroprotection and enhancing nerve repair in patients with GBS. PMID- 22046449 TI - Temporal responses of wild-type pigmentation and RcaE-deficient strains of Fremyella diplosiphon during light transitions. AB - A temporal study was conducted to evaluate the dynamic complementary chromatic adaptation (CCA) response of two Fremyella diplosiphon strains-wild-type pigmentation strain SF33 and an RcaE-deficient (DeltarcaE) strain, which lacks the photosensor that regulates CCA. SF33 and DeltarcaE cultures were monitored for 15 days after transition of green-light (GL) acclimated cultures to red light (RL) and vice versa. SF33 showed similar growth irrespective of the external light quality; however, a DeltarcaE strain grew slower than SF33 under both RL and GL. Chlorophyll a (chla) content increased in both strains over time and was not much different under RL and GL indicating that chla biosynthesis is not affected significantly by light quality or RcaE function. Phycoerythrin is the sole pigment to absorb GL, whereas several pigments, i.e., allophycocyanin, phycocyanin and chla, function under RL to drive photosynthesis. SF33 compensates for this by synthesizing a higher percentage of PE under GL. The final pigment distribution in the DeltarcaE mutant was found to be more different from SF33 under GL than under RL indicating that RcaE is needed for a transitional response to RL and RL-dependent repression of PE accumulation, yet RcaE is virtually critical for both transitioning to and a full adaptation to GL. PMID- 22046450 TI - Nuclear actin: A key player in extracellular matrix-nucleus communication. AB - Decades of research have shown that there is an intimate relationship between the extracellular matrix (ECM) and cellular phenotype. While the existence of this relationship remains inarguably clear, the exact details through which the extracellular matrix controls phenotypic behavior at the gene expression level are, for the most part, elusive. In a recent study on mammary epithelial cells, nuclear actin was identified as a key effector protein through which laminin Type III (LN1) attenuates RNA polymerase activity to promote growth arrest. This finding forms the basis from which one can begin to envision a mechanism through which the ECM can control nuclear function to enact changes in cell behavior. Here I will briefly discuss the current depth of knowledge with regards to the relationship between LN1 and nuclear actin and its implication in mammary epithelial cell growth and function. PMID- 22046451 TI - Regulation of neuronal functions by the E3-ubiquitinligase protein associated with MYC (MYCBP2). AB - The E3-ubiquitinligase MYCBP2 regulates neuronal growth, synaptogenesis and synaptic plasticity by modulating several signaling pathways including the p38 MAPK signaling cascade. We found that loss of MYCBP2 in peripheral sensory neurons inhibits the internalization of transient receptor potential vanilloid receptor 1 (TRPV1) in a p38 MAPK-dependent manner. This prevented desensitization of activity-induced calcium increases and prolongs formalin-induced thermal hyperalgesia in mice. Besides its function in pain perception TRPV1 is also involved in the regulation of neuronal growth. Therefore, the observed effect of MYCBP2 on TRPV1 internalization could be part of the mechanisms underlying its well documented regulatory role in neuronal growth. The clarification of the mechanism is important for the understanding of the different MYCBP2-functions in diverse neuronal subpopulations and species. PMID- 22046452 TI - Can mathematics explain the evolution of human language? AB - Investigation into the sequence structure of the genetic code by means of an informatic approach is a real success story. The features of human language are also the object of investigation within the realm of formal language theories. They focus on the common rules of a universal grammar that lies behind all languages and determine generation of syntactic structures. This universal grammar is a depiction of material reality, i.e., the hidden logical order of things and its relations determined by natural laws. Therefore mathematics is viewed not only as an appropriate tool to investigate human language and genetic code structures through computer science-based formal language theory but is itself a depiction of material reality. This confusion between language as a scientific tool to describe observations/experiences within cognitive constructed models and formal language as a direct depiction of material reality occurs not only in current approaches but was the central focus of the philosophy of science debate in the twentieth century, with rather unexpected results. This article recalls these results and their implications for more recent mathematical approaches that also attempt to explain the evolution of human language. PMID- 22046453 TI - Ion-selective self-referencing probes for measuring specific ion flux. AB - The metal vibrating probe developed in the 1970s to measure electric current is sensitive down to the micro-Amp range, but detects only net current due to flow of multiple ions and is too large to measure from single cells. Electrophysiological techniques which use glass microelectrodes such as voltage clamping can be used on single cells but are also non-specific. Ion-selective probes are glass microelectrodes containing at their tip a small amount of ionophore permeable to a particular ion. The electrode is therefore sensitive to changes in concentration of this ion. If the probe tip is moved at low frequency between two points in a concentration gradient of this ion then the electrochemical potential of the solution inside the electrode fluctuates in proportion to the size of the ion gradient. This fluctuation is amplified and recorded and is used to calculate the actual ion flux using Fick's law of diffusion. In this mini-review we describe the technique of ion-selective self referencing microelectrodes to measure specific ion fluxes. We discuss the development of the technique and describe in detail the methodology and present some representative results. PMID- 22046454 TI - A tale of two sites: How ubiquitination of a G protein-coupled receptor is coupled to its lysosomal trafficking from distinct receptor domains. AB - The beta(2)-adrenergic receptor (beta(2)AR) is a prototypical G(s)-coupled receptor belonging to the superfamily of seven transmembrane spanning heptahelical receptors (7TMRs or G protein-coupled receptors [GPCRs]) therapeutically the most diverse and accessible class of cell surface receptors. The classic pathway of beta(2)AR signaling (Fig. 1) is triggered by activation of the heterotrimeric G protein G(s) by agonists (catecholamines-noradrenaline and adrenaline). This in turn activates adenylyl cyclase leading to the generation of second messenger signaling molecules (cyclic adenosine monophosphates, cAMP) which subsequently activate protein kinase A (PKA) as well as some ion channels, such as the class C type of L-type calcium channels, Ca(v)1.2.31 Here in we review how trafficking and signaling of the beta(2)AR is regulated by the post translational modification, ubiquitination.1. PMID- 22046455 TI - Intraluminal volume homeostasis: A common sertonergic mechanism among diverse epithelia. AB - Volume homeostasis is a common physiological phenomenon for fluid secreting organs, such as exocrine and endocrine glands. It is a manifestation of a finite intraluminal space and an ever changing demand for secretory fluids. Volume homeostasis addresses issues of fluid secretion, storage and clearance for efficient functioning. Here we discuss the evidence gathered over the past 2-3 decades on serotonin's role as a feedback inhibitor of secretion in the mammary gland, salivary gland, liver, pancreas, lung, thyroid gland and prostate gland. We propose that serotonin action is a common mechanism of regulating intraductal volume homeostasis. PMID- 22046456 TI - DAAM family members leading a novel path into formin research. AB - Formins are an important and evolutionarily well conserved class of actin binding proteins with essential biological functions. Although their molecular roles in actin regulation have been clearly demonstrated in vitro, their functions at the cellular or organism levels are still poorly understood. To illustrate this problem, but also to demonstrate potential ways forward, we focus here on the DAAM group of formins. In vertebrates, DAAM group members have been demonstrated to be important regulators of cellular and tissue morphogenesis but, as for all formins, the molecular mechanisms underlying these morphogenetic functions remain to be uncovered. The genome of the fruitfly Drosophila encodes a single DAAM gene that is evolutionarily highly conserved. Recent work on dDAAM has already provided a unique combination of observations and experimental opportunities unrivalled by any other Drosophila formin. These comprise in vitro actin polymerisation assays, subcellular studies in culture and in vivo, and a range of developmental phenotypes revealing a role in tracheal morphogenesis, axonal growth and muscle organization. At all these levels, future work on dDAAM will capitalize on the power of fly genetics, raising unique opportunities to advance our understanding of dDAAM at the systems level, with obvious implications for other formins. PMID- 22046458 TI - The yolk cell of the zebrafish blastula harbors functional apoptosis machinery. AB - We recently described the implication of the Bcl-2 related antiapoptotic Nrz protein during early zebrafish development. Nrz knock-down induces calcium dependent cytoskeleton remodeling leading to margin constriction and premature embryo lethality. In the YSL, nrz knock-down embryos exhibit some typical features of apoptosis such as mitochondrial transmembrane potential loss and cytochrome c release. However, downstream caspase-3 activation has not been detected so far. Here, we report that the YSL contains fully functional apoptotic machinery that can activate caspase-3 following zBax ectopic expression. Furthermore, we present evidence that caspase-3 activation is actually detectable in nrz knock-down embryos when premature margin constriction is prevented. PMID- 22046457 TI - The diverse functions of short-term plasticity components in synaptic computations. AB - Short-term plasticity (STP) comprises several rapid synaptic processes that operate on millisecond-to-minute timescales and modulate synaptic efficacy in an activity-dependent manner. Facilitation and augmentation are two major STP components in central synapses that work to enhance synaptic strength, while various forms of short-term depression work to decrease it. These multiple components of STP interact to perform a variety of synaptic computations. Using a modeling approach in excitatory hippocampal synapses, we recently described the contributions of individual STP components to synaptic operations. In this mini review, we summarize the recent findings that revealed a wide palette of functions that STP components play in neural operations and discuss their roles in information processing, working memory and decision making. PMID- 22046459 TI - Assembly and breakdown of microtubules within the midbody. AB - In animal cells, cell division concludes with the separation of two daughter cells during a process called cytokinesis. Abscission, the termination of cytokinesis, is performed through formation of the midbody, a vis-a-vis microtubule (MT)-rich structure bridging the daughter cells. Disassembly of the midbody is the final stage of daughter cell separation and occurs in parallel to membrane fusion in this area. To shed light on this process and to better understand MT organization within the dense area of the midbody structure, an integrative fluorescence microscopy and cryo-electron tomography (cryo-ET) approach was taken.1 These efforts led to a resolving of MT architecture at single-fiber resolution, resulting in a refined model of abscission. PMID- 22046460 TI - Tao kinases as coordinators of actin and microtubule dynamics in developing neurons. AB - Drosophila tao, encoding a Ste20 family kinase, was identified as a gene involved in ethanol, cocaine and nicotine sensitivity. The behavioral phenotypes appear to be caused by defects in the development of the adult brain. Specifically, Drosophila tao functions to promote axon guidance of mushroom body (MB) neurons. The MB is a large structure in the central brain of the fly whose development and function have been well characterized. tao interacts genetically with mutations in the par-1 gene, also encoding a serine-threonine kinase. Since Par-1 has been implicated in the regulation of microtubule dynamics, this suggests that tao regulates the microtubule cytoskeleton in developing MB neurons. Here we discuss these results in light of previous studies that have proposed that Drosophila tao and its mammalian homologs function as a link between the actin and microtubule cytoskeletons, regulating microtubule stability in response to actin signals. PMID- 22046461 TI - FG repeats facilitate integral protein trafficking to the inner nuclear membrane. AB - The mechanism for nucleo-cytoplasmic transport of integral membrane proteins is poorly understood compared to transport of soluble molecules. We recently demonstrated that at least four distinct mechanisms can contribute to transport of integral proteins through the peripheral channels of the nuclear pore complex. One of these requires having multiple phenylalanine-glycine (FG) pairings on the integral protein. It also requires the nuclear pore complex protein Nup35, which separately contains FG repeats. FG-repeats on nuclear pore complex proteins in the central channel have been proposed to interact with FGs on transport receptors to facilitate transport of soluble proteins. Here we show that FG repeats occur quite frequently in both transmembrane and soluble proteins identified in multiple separate proteomic analyses of nuclear envelopes. We postulate that the FG repeats enable these proteins to function as their own transport receptors. PMID- 22046462 TI - How and why does Dia1 mRNA localize? AB - Messenger RNA (mRNA) localization plays an important role in various cellular functions. To date, two general mechanisms have been identified for intracellular mRNA localization. The first one was identified by Blobel and colleagues more than three decades ago, by which mRNAs encoding for membrane and secreted proteins are targeted to the endoplasmic reticulum (ER) in a signal peptide dependent manner.1 The second mechanism is for the intracellular targeting of mRNAs encoding cytosolic proteins, which is dependent on specific sequence on the mRNA called zipcode.2 Recently, we have identified a new mechanism which targets Dia1 mRNA to the perinuclear ER in a zipcode-independent manner, even though the mRNA encodes a cytosolic protein.3 Here, we provide an updated discussion on how the Dia1 mRNA is targeted and what might be its physiological significance. PMID- 22046463 TI - Physicochemical influence on odor hedonics: Where does it occur first? AB - We recently reported data showing that, while human olfactory pleasantness is modulated by semantic knowledge of smells, the physicochemical aspects of odorant molecules are prominent determinants of odor hedonic valence, especially in children and seniors, two age groups characterized by either low level of (children) or weak access to (seniors) odor semantic knowledge.1 Here, we present additional data from a human and an animal study, confirming that odorant structure predicts odor pleasantness and suggesting that this influence may be already engraved at receptor level. PMID- 22046464 TI - Imaging functional neural circuits in zebrafish with a new GCaMP and the Gal4FF UAS system. AB - Measurement of the activity of neuronal ensembles is an essential step to understand how the neuronal network is organized and functioning. Electrical excitation of neurons causes calcium influx via voltage-gated calcium ion channels, which can be monitored by calcium imaging using fluorescent calcium probes. DNA-encoded calcium indicators (DECIs) such as cameleon and GCaMP have been developed to specifically label a subpopulation of neurons. However, in many cases, DECIs that had been developed and tested in vitro did not always show expected performance in vivo. It is necessary to increase its sensitivity and also to adjust its dynamic range to the physiological conditions. In our recent study, we developed an improved version of GCaMP and tested its performance in vivo using transgenic zebrafish. By combining the new GCaMP with targeted gene expression via the Gal4FF-UAS system, we successfully imaged the activity of the spinal motor circuit during spontaneous contractions of zebrafish larvae. Further we report here that heptanol, a gap junction blocker, could alter the spatiotemporal activation pattern of the motor circuit. Thus, we demonstrate that calcium imaging with GCaMP is powerful to analyze neuronal activities under normal and pharmacologically perturbed conditions. PMID- 22046465 TI - Brain area specific regulation of synaptic AMPA receptors by phosphorylation. AB - Regulation of synaptic AMPA receptors (AMPARs) is one of the key elements that allow the nervous system to adapt to changes in the sensory environment as well as for memory formation. One way to regulate AMPAR function is by reversible changes in the phosphorylation of its subunits. We recently reported that phosphorylation of the AMPAR subunit GluA1 (or GluR1) on serine-845 (S845) is a pre-requisite step for sensory experience-dependent homeostatic synaptic plasticity in the visual cortex. In particular, increasing GluA1-S845 phosphorylation upregulated cell surface and synaptic AMPAR levels. Here we report that this is rather specific to the visual cortex, in that increasing GluA1-S845 phosphorylation in hippocampal slices only increase cell surface expression, but not synaptic AMPAR function. Our results suggest that depending on the brain region divergent mechanisms may exist to regulate synaptic AMPAR function with phosphorylation. PMID- 22046466 TI - What are we measuring with GABA magnetic resonance spectroscopy? AB - A number of recent papers1-3 have demonstrated a relationship between in vivo concentration of GABA, as assessed using Magnetic Resonance Spectroscopy (MRS), and an individual's task performance, giving a unique insight into the relationship between physiology and behavior. However, interpretation of the functional significance of the MRS GABA measure is not straightforward. Here we discuss some of the outstanding questions as to how total concentration of GABA within a cortical region relates to phasic and tonic GABA activity within the cortical volume studied. PMID- 22046467 TI - Emerging roles of phosphoinositide-specific phospholipases C in the ciliates Tetrahymena and Paramecium. AB - Phospholipases C (PLCs) that hydrolyze inositol phospholipids regulate vital cellular functions in both eukaryotic and prokaryotic organisms. The PLC superfamily consists of eukaryotic phosphoinositide-specific PLCs (PI-PLCs), bacterial PLCs and trypanosomal PLCs.1 PI-PLCs hydrolyze phosphatidylinositol-4,5 bisphosphate (PtdIns4,5P(2)) to produce inositol-1,4,5-trisphosphate (Ins1,4,5P(3)) and constitute a hallmark feature of eukaryotic cells. In metazoa, this reaction is coupled to receptor signaling via specific PI-PLC isoforms and results in acute increase of cytosolic Ca(2+) levels by Ins1,4,5P(3)-sensitive Ca(2+) channels (IP(3)-receptors, IP3Rs).2 A striking result of many studies so far has been the presence of a single PI-PLC gene in all unicellular eukaryotes investigated, as opposed to expansion of PI-PLC isoforms in metazoa;3 this has suggested that a single housekeeping PI-PLC represents an archetypal and simplified form of PI-PLC signaling.3 Several studies however have noted a unique expansion of PI-PLC/IP3R pathway components in ciliates.4,5 In a recent paper we showed the presence of multiple functional PI-PLC genes in Tetrahymena thermophila and biochemical characterization, pharmacological studies and study of their expression patterns suggested that they are likely to serve distinct non redundant roles.4 In this report we discuss these studies and how they advance our understanding of PI-PLC functions in ciliates. PMID- 22046468 TI - The regulation and role of neuronal gap junctions during development. AB - Coupling of neurons by electrical synapses (gap junctions) transiently increases in the mammalian CNS during development and plays a role in a number of developmental events, including neuronal death. The coupling subsequently decreases and remains low in the adult, confined to specific subsets of neurons. In a recent study we have demonstrated that the developmental increase in neuronal gap junction coupling is regulated by the balance between the activity of two neurotransmitter receptors, group II metabotropic glutamate receptors (mGluR) and GABA(A) receptors. Specifically, we found that activation of group II mGluRs induces the developmental increases in neuronal gap junction coupling and expression of connexin 36 (Cx36; neuronal gap junction protein) and activation of GABA(A) receptors counteracts to these increases. We also established that the regulation by both neurotransmitter receptors is via a neuron-restrictive silencer element in the Cx36 gene promoter and the 3'-untranslated region of the Cx36 mRNA. Importantly, we demonstrated that mechanisms for the developmental increase in neuronal gap junction coupling directly control the death/survival mechanisms in developing neurons. PMID- 22046469 TI - Nuclear actin and transcriptional activation. AB - Differentiated cells do not revert to an embryonic state in normal development. However, the method called nuclear reprogramming enables these differentiated cells to be reversed to an embryonic state. One essential event in the reprogramming process is reactivation of embryonic genes such as Oct4 (also known as Pou5f1). This reprogramming of transcriptional programs can be achieved by transplantation of mammalian somatic nuclei to the giant Xenopus laevis oocyte nucleus, referred to as the germinal vesicle (GV). Factors and mechanisms responsible for this transcriptional reprogramming have not been elucidated. Recently, we have found that a polymerized form of actin is abundantly present in nuclei transplanted into the Xenopus oocyte nucleus and plays an important role in transcriptional reactivation of Oct4. This study emphasizes a significant contribution of nuclear actin in transcriptional activation. Here, we discuss possible roles of nuclear actin in Xenopus oocytes and in other cell types in the context of transcriptional activation. PMID- 22046470 TI - Nitric oxide regulates non-classical secretion of tissue transglutaminase. AB - Nitric oxide (NO) is an endogenous second messenger which acts as a potent vasodilator, anti-inflammatory, anti-thrombotic and pro-angiogenic agent in the vasculature. Recent studies revealed that the effects of NO on blood vessels are mediated in part by its ability to regulate protein trafficking machinery and vesicle-based exocytosis in vascular cells. Specifically, NO-dependent S nitrosylation of N-ethylmaleimide sensitive factor (NSF), an ATPase that enables membrane fusion, was shown to inhibit exocytosis of vesicular secretory compartments such as endothelial Weibel-Palade bodies, platelet alpha granules and cytolytic granules from activated lymphocytes. Tissue transglutaminase (tTG or TG2) is a multifunctional protein synthesized and secreted by various cell types in the vasculature, which is involved in multiple vascular diseases, including atherosclerosis, vascular calcification and age-dependent aortic stiffening. Our recent findings indicate that tTG is delivered to the cell surface and the extracellular matrix (ECM) via a non-classical ER/Golgi independent secretion pathway, which depends on the recycling endosomes and the NSF function. Here we report that NO attenuates the unconventional secretion of tTG in human aortic endothelial cells. NO-dependent downregulation of extracellular tTG levels via inhibition of its secretion might be a part of general physiological mechanism which limits externalization of adhesive, pro inflammatory and thrombogenic proteins in the vasculature. PMID- 22046471 TI - Cell entry and exit by periodontal pathogen via recycling pathway. AB - In the oral cavity, gingival epithelial cell (GEC) layers function as an innate host defense system to prevent intrusion by periodontal bacteria. Nevertheless, Porphyromonas gingivalis, the most well-known periodontal pathogen, can enter GECs and pass through the epithelial barrier into deeper tissues. An intracellular location is considered advantageous for bacteria to escape from immune surveillance by the host as well as antibiotic pressure, leading to intracellular persistence, multiplication and dissemination to adjacent tissues. P. gingivalis are invaginated by gingival epithelial cells via the endocytic pathway, and some intracellular bacteria are sorted to lytic compartments, including autolysosomes and late endosomes/lysosomes, while a considerable number of the remaining organisms are sorted to Rab11- and RalA-positive recycling endosomes, followed by bacterial exit from the cells. Exited bacteria can re enter fresh cells. However, dominant negative forms and RNAi-knockdown of Rab11, RalA and exocyst complex subunits (Sec5, Sec6 and Exo84) significantly disturb the exit of P. gingivalis. These are the first known results to show that the endocytic recycling pathway mediates bacterial exit from infected cells to neighboring cells and may provide important information regarding the exit mechanisms of various invasive pathogens. PMID- 22046472 TI - Golgi-associated Rab14, a new regulator for Chlamydia trachomatis infection outcome. AB - Chlamydia trachomatis is the causing agent of the most frequent bacterial sexually-transmitted diseases worldwide and is an underlying cause of chronic pelvic inflammatory diseases and cervical cancer. It is an obligate intracellular bacterium that establishes a close relationship with the Golgi complex and parasites the biosynthetic machinery of host cells. In a recent study, we have demonstrated that Rab14, a newly-described Golgi-associated Rab, is involved in the delivery of sphingolipids to the growing bacteria-containing vacuole. The interference with Rab14-controlled trafficking pathways delays chlamydial inclusion enlargement, decreases bacterial lipid uptake, negatively impact on bacterial differentiation, and reduces bacterial progeny and infectivity. C. trachomatis manipulation of host trafficking pathways for the acquisition of endogenously-biosynthesized nutrients arises as one of the characteristics of this highly evolved pathogen. The development of therapeutic strategies targeted to interfere with bacterium-host cell interaction is a new challenge for pharmacological approaches to control chlamydial infections. PMID- 22046473 TI - To bee or not to bee, this is the question...: The inborn numerical competence of humans and honeybees. AB - Human inborn numerical competence means our ability to recognize object numbers precisely under circumstances which do not allow sequential counting. This archaic process has been called "subitizing," from the Latin "subito" = suddenly, immediately, indicating that the objects in question are presented to test persons only for a fraction of a second in order to prevent counting. In contrast, however, sequential counting, an outstanding cultural achievement of mankind, means to count "1, 2, 3, 4, 5, 6, 7, 8..." without a limit. The following essay will explain how the limit of numerical competence, i.e., the recognition of object numbers without counting, has been determined for humans and how this has been achieved for the first time in case of an invertebrate, the honeybee. Finally, a hypothesis explaining the influence of our limited, inborn numerical competence on counting in our times, e.g., in the Russian language, will be presented. Subitizing versus counting by young Down syndrome infants and autistics and the Savant syndrome will be discussed. PMID- 22046474 TI - Ophiocordyceps unilateralis: A keystone species for unraveling ecosystem functioning and biodiversity of fungi in tropical forests? AB - Ophiocordyceps unilateralis (Ascomycota: Hypocreales) is a specialized parasite that infects, manipulates and kills formicine ants, predominantly in tropical forest ecosystems. We have reported previously, based on a preliminary study in remnant Atlantic Forest in Minas Gerais (Brazil), that O. unilateralis represents a species complex. On each of the four species of infected carpenter ant (Camponotus) collected, the fungus-characterized macroscopically by a single stalk arising from the dorsal neck region on which the sexual structures (stromatal plates) are borne laterally-can readily be distinguished both microscopically and functionally. Here, we describe and discuss the biology, life cycle and infection strategies of O. unilateralis s.l. and hypothesize that there may be hundreds of species within the complex parasitizing formicine ants worldwide. We then address the diversity within related hypocrealean fungi, with particular reference to symbionts (mutualists through to parasites), and argue that the widely-quoted total of extant fungi (1.5 million species) may be grossly underestimated. PMID- 22046475 TI - Heterogeneous release probabilities and activity-dependent short-term synaptic depression. AB - Synaptic transmission is a major mechanism by which neurons communicate with each other. Basic steps in neurotransmitter release are similar in all synapses. However, many properties of release vary between synapses and reflect specific structural and functional requirements, endowing synapses with specialized functions. Recently, Gelman et al.1 described properties of release and short term depression at specialized nicotinic synapses in the brainstem of goldfish, Carassius auratus (Linnaeus). These axo-axonic synapses between the Mauthner cell collaterals and their targets, cranial relay neurons (CRNs), exhibit strong short term depression, even at stimulation frequencies as low as 0.33 Hz. In short, amplitudes of post-synaptic responses, evoked by presynaptic trains of action potentials, were depressed with a time course approximated by a sum of two exponential functions. Initially, fast depression reduced the amplitude of EPSP(2) (response after the second stimulus), to less than 50% of EPSP(1) (response after the first stimulus). This was followed by a slow component of depression that produced an additional 10-30% amplitude reduction over a time span of tens to hundreds of seconds. Interestingly, depressed EPSPs exhibited longer latencies than that of the "undepressed" EPSP1. Additionally, fast and slow calcium chelators (BAPTA and EGTA), injected pre-synaptically, were equally potent in reducing release. These data are consistent with a previously proposed general mechanism that assumes a change in release probability after the initial release. However, in an alternative interpretation the results could be coherently explained by postulating two releasable pools of vesicles, with high and low release probabilities, and a generally accepted depletion scheme. This latter interpretation will be discussed in this article. PMID- 22046476 TI - ESCRT or endosomes?: Tales of the separation of two daughter cells. AB - The final abscission event of cytokinesis is necessary for daughter cells to part ways from one another. Failure to properly divide has been indicated as a potential cancer initiating event due to an increase in cellular aneuploidy. However, the exact mechanisms of abscission have remained obscured by our inability to properly discern the spatiotemporal regulation of the various proteins and organelles required for cytokinesis. Three recent publications have taken slightly varied high resolution imaging approaches to visualize cytokinesis and abscission. As a result of this work, two differing, but not necessarily mutually exclusive, models have emerged. One model is ESCRT-dependent and the other, recycling endosome-dependent, each describing the steps leading up to the final abscission event. Presently these models describe late cytokinesis events leading to abscission in greater detail than previously known. PMID- 22046477 TI - Can alternative pathways mediate the influence of queen number on nestmate discrimination in ants? AB - The evolution of social life is usually associated with capabilities of individuals to protect group boundaries against foreign individuals. In colonies of ants, the number of reproductive queens is known to influence the accuracy of nestmate discrimination by resident workers. However, the pathway by which this effect is mediated remains unclear. The major hypothesis has long been that workers from multiple-queen colonies commit more discrimination errors against foreigners because their colonies contain a broader diversity of genetically determined cues characterising colony membership. Until recently, this hypothesis has received little attention and poor empirical support. In a recent study, Meunier et al.1 proposed an alternative, albeit not mutually exclusive hypothesis. The presence of one or multiple queens modifies chemical signals on colony members that trigger aggressive or cooperative behaviors during foreign encounters. Here, I detail how this new hypothesis is congruent with previous results and discuss potential limits and evolutionary implications of the two suggested hypotheses. PMID- 22046478 TI - Homeostasis of the Drosophila adult retina by actin-capping protein and the Hippo pathway. AB - The conserved Hippo signaling pathway regulates multiple cellular events, including tissue growth, cell fate decision and neuronal homeostasis. While the core Hippo kinase module appears to mediate all the effects of the pathway, various upstream inputs have been identified depending on tissue context. We have recently shown that, in the Drosophila wing imaginal disc, actin-Capping Protein and Hippo pathway activities inhibit F-actin accumulation. In turn, the reduction in F-actin sustains Hippo pathway activity, preventing Yorkie nuclear translocation and the upregulation of proliferation and survival genes. Here, we investigate the role of Capping Protein in growth-unrelated events controlled by the Hippo pathway. We provide evidence that loss of Capping Protein induces degeneration of the adult Drosophila retina through misregulation of the Hippo pathway. We propose a model by which F-actin dynamics might be involved in all processes that require the activity of the core Hippo kinase module. PMID- 22046479 TI - The role of the membrane confinement in the surface area regulation of cells. AB - We propose a new in vitro system to study the mechanics of surface area regulation in cells, which takes into an account the spatial confinement of the cell membrane. By coupling a lipid bilayer to the strain-controlled deformation of an elastic sheet, we show that upon straining the supported lipid bilayer expands its surface area by absorbing adherent lipid vesicles and upon compression decreases its area by expelling lipid tubes out of its plane. The processes are reversible and closely resemble in vivo observations on shrinking cells. Our results suggest that the mechanics of the area regulation in cells is controlled primarily by the membrane tension and the effects of the membrane confinement. PMID- 22046480 TI - Evolutionary variations of VPS29, and their implications for the heteropentameric model of retromer. AB - The retromer complex is conserved across all eukaryotic species and functions in physiologically important sorting processes at the endosomal membrane. A key component of retromer is the VPS29 protein that, although structurally similar to phospho-diesterases, has been convincingly shown in the recent study by Swarbrick et al. (PLoS One 6:e20420, 2011) to be a rigid scaffold that interacts with various proteins that function with retromer in endosomal protein sorting. A widely held view, based on initial observations in Saccharomyces cerevisiae, is that retromer functions as a stable heteropentamer. This is, however, contrary to experimental data presented in Swarbrick et al. (and in other studies) that indicate that retromer in higher eukaryotes is a looser association of two subcomplexes that respectively mediate cargo-selection and membrane tubulation. Here we present an analysis of evolutionary variation of the VPS29 protein and discuss why the retromer complex as first characterized in S. cerevisiae is not representative of retromer in other eukaryotic taxa. PMID- 22046481 TI - Cytoplasmic to nuclear localization of fatty-acid binding protein correlates with specific forms of long-term memory in Drosophila. AB - We recently reported evidence implicating fatty-acid binding protein (Fabp) in the control of sleep and memory formation. We used Drosophila melanogaster to examine the relationship between sleep and memory through transgenic overexpression of mouse brain-Fabp, Fabp7, or the Drosophila Fabp homolog, (dFabp). The key findings are that 1) a genetically induced increase in daytime consolidated sleep (naps) correlates with an increase in cognitive performance, and 2) a late "window" of memory consolidation occurs days after the traditionally understood "synaptic" consolidation. Exactly how Fabp-signaling may be involved in converting normal to enhanced long-term memory (LTM) is not known. Here we describe additional data which support relative subcellular compartmental localization of Fabp in regulating stage associations of different forms of memory in Drosophila. Anesthesia resistant memory (ARM) is a longer lasting memory that is produced by massed training, but unlike LTM produced by spaced training, it is insensitive to protein synthesis inhibitors and does not persist as long. We observed that the ratio of ARM to LTM performance index of Fabp7 transgenic flies is proportional to the relative cytoplasmic to nuclear Fabp7 expression level. These data suggest a common lipid-signaling cascade exists between phases of memory formation previously thought to be molecularly distinct. PMID- 22046482 TI - The evolution and role of mitochondrial fusion and fission in aging and disease. AB - Mitochondria contain their own genetic material and evolved from prokaryotic ancestors some two billion years ago. They are the main source of the cell's energy supply and are involved in such important processes as apoptosis, mitochondrial diseases and aging. Mitochondria display a complex dynamical behavior involving cycles of fusion and fission, the function of which is as yet unknown. We recently proposed a concise theory that explains: (1) why fusion and fission have evolved, (2) how these processes relate to the accumulation of mitochondrial mutants during aging and (3) why mtDNA is located close to the respiration complexes where most radicals are generated. We also believe that this 'organelle control' theory may explain why mutations in mitochondrial tRNA genes are the most prevalent kind of defect associated with inherited human mitochondrial diseases, despite the fact that mt-tRNA genes account for only 5% of the mtDNA coding sequence. PMID- 22046483 TI - Strategies to harness immunity against infectious pathogens after haploidentical stem cell transplantation. AB - Viral and fungal infections account for significant morbidity and mortality, particularly in pediatric patients with profound immune suppression resulting from allogeneic hematopoietic stem cell transplantation (HSCT). Therapies with anti-viral and anti-fungal drugs are often associated with significant toxicity, are of limited efficacy and can induce drug resistance. One innovative approach to prevent and/or treat viral and fungal infections involves the adoptive transfer of in vitro-expanded or in vitro-generated pathogen-specific T cells. This review summarizes the clinical trials that have been run to date with virus- and fungus-specific T cells, with special emphasis on the clinical context of haploidentical HSCT for pediatric malignancies. It will also discuss initiatives and strategies to overcome the hurdles associated with time-consuming and complex GMP-grade laboratory procedures required to generate pathogen-specific T cells. PMID- 22046484 TI - Translational research: current status, challenges and future strategies. AB - Advances in translational research are expected to mitigate the recent drought in new drug development. Despite significant progress recently made in biological sciences, the results are decidedly mixed with significant breakthrough in some disease areas while extensive work remains to be completed in other areas. This review article provides a general survey of the current landscape of translational research so as to identify progress and areas of needs and the associated strategy. While significant advances in the development of translational tools have been made in all fronts, the availability of predictive preclinical models remains critical for the success of translational research. This is directly correlated with the success of translational research as illustrated by the recent approval of targeted drug therapies. By the same logic, unexpected side effects can also be explained by laboratory findings, thus completing the translational cycle. Because of this reason, further collaboration between preclinical and clinical scientists is essential. Non-scientific issues have important influence on the future of this endeavor cannot be underestimated either. Nonetheless, with definitive commitment of private industry and public resources, the future of translational research is promising. PMID- 22046485 TI - Emerging drug discovery approaches for selective targeting of "precursor" metastatic breast cancer cells: highlights and perspectives. AB - Breast cancer is a prevalent disease and a major cause of morbidity and cancer related deaths among women worldwide. A significant number of patients at the time of primary diagnosis present metastatic disease, at least to locoregional lymph nodes, which results in somewhat unpredictable prognosis that often prompts adjuvant systemic therapies of various kinds. The time course of distant recurrence is also unpredictable with some patients sustaining a recurrence within months after diagnosis, even during adjuvant treatments, while others can experience recurrence years or decades after initial diagnosis. To date, clinically approved therapeutics yielded marginal benefits for patients with systemic metastatic breast disease, since despite high clinical responses to various therapies, the patients virtually always become resistant and tumor relapses. Molecular profiling studies established that breast cancer is highly heterogeneous and encompasses diverse histological and molecular subtypes with distinct biological and clinical implications in particular in relation to the incidence of progression to metastasis. The latter has been recognized to result from late genetic events during the multistep progression proposed by the dominant theory of carcinogenesis. However, there is evidence that the dissemination of primary cancer can also be initiated at a very early stage of cancer development, originating from rare cell variants, possibly cancer stem like cells (CSC), with invasive potential. These precursor metastatic cancer cells with stem-like properties are defined by their ability to self-renew and to regenerate cell variants, which have high plasticity and intrinsic invasive properties required for dissemination and tropism toward specific organs. Equally relevant to the CSC hypothesis for metastasis formation is the epithelial mesenchymal transition (EMT) process, which is critical for the acquisition of cancer cell invasive behavior and for selection/gain of CSC properties. These exciting concepts have led to the formulation of various approaches for targeting precursor metastatic cells, and these have taken on greater priority in therapeutic drug discovery research by both academia and pharmaceuticals. In this review, we focus on current efforts in medicinal chemistry to develop small molecules able to target precursor metastatic cells via interference with the CSC/EMT differentiation program, self-renewal, and survival. It is not meant to be comprehensive and the reader is referred to selected reviews that provide coverage of related basic aspects. Rather, emphasis is given to promising molecules with CSC/EMT signaling at the preclinical stage and in clinical trials that are paving the way to new generations of anti-metastasis drugs. PMID- 22046486 TI - The clinical value of von Willebrand factor in colorectal carcinomas. AB - BACKGROUND: To identify the value of von Willebrand factor (vWF) as a clinical marker in colorectal carcinoma (CRC). METHODS: Plasma levels of vWF were measured in 79 patients with UICC Stage I-IV CRC at time of operation and correlated with TNM categories, levels of the carcinoembryonic antigen (CEA), blood groups (BG) and 19 controls (CO). CO included cancer-free patients without bacterial or viral infections. For tissue analysis paraffin embedded tumour and mucosa sections of operation specimens were stained immunohistochemically for vWF and compared to vWF plasma levels as well as to TNM categories. RESULTS: VWF plasma levels in CRC patients were significantly dependent on blood groups (p=0.012) and elevated compared to the normal ranges as well as to controls (BG 0: p=0.668, BG A/AB/B: p=0.020). CRC-Patients over 60 years of age presented with significantly higher vWF levels than patients below 60 years (BG 0: p=0.005; BG A/AB/B: p=0.035). There was no correlation of vWF plasma levels and UICC stages in CRC. Patients with elevated vWF plasma levels also presented with elevated CEA levels, but significance was missing (p=0.080). VWF concentration within the tumour tissue was independent of concentration within normal mucosa, blood groups, histopathological characteristics and did not correlate with plasma vWF levels. CONCLUSION: VWF plasma levels are elevated in CRC patients, but not in a stage dependent manner. Besides the tumour at least blood groups and age mainly influence plasma vWF levels. In our opinion vWF as a routinely used clinical marker in CRC cannot be recommended. PMID- 22046487 TI - Potential non-oncological applications of histone deacetylase inhibitors. AB - Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutic drugs. Their clinical utility in oncology stems from their intrinsic cytotoxic properties and combinatorial effects with other conventional cancer therapies. To date, the histone deacetylase inhibitors suberoylanilide hydroxamic acid (Vorinostat, Zolinza(r)) and depsipeptide (Romidepsin, Istodax(r)) have been approved by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Further, there are currently over 100 clinical trials involving the use of histone deacetylase inhibitors in a wide range of solid and hematological malignancies. The therapeutic potential of histone deacetylase inhibitors has also been investigated for numerous other diseases. For example, the cytotoxic properties of histone deacetylase inhibitors are currently being harnessed as a potential treatment for malaria, whereas the efficacy of these compounds for HIV relies on de-silencing latent virus. The anti-inflammatory properties of histone deacetylase inhibitors are the predominant mechanisms for other diseases, such as hepatitis, systemic lupus erythematosus and a wide range of neurodegenerative conditions. Additionally, histone deacetylase inhibitors have been shown to be efficacious in animal models of cardiac hypertrophy and asthma. Broad-spectrum histone deacetylase inhibitors are clinically available and have been used almost exclusively in preclinical systems to date. However, it is emerging that class- or isoform-specific compounds, which are becoming more readily available, may be more efficacious particularly for non-oncological applications. The aim of this review is to provide an overview of the effects and clinical potential of histone deacetylase inhibitors in various diseases. Apart from applications in oncology, the discussion is focused on the potential efficacy of histone deacetylase inhibitors for the treatment of neurodegenerative diseases, cardiac hypertrophy and asthma. PMID- 22046488 TI - LAT1 expression is closely associated with hypoxic markers and mTOR in resected non-small cell lung cancer. AB - AIM: L-type amino acid transporter 1 (LAT1) is known to be highly expressed in various human neoplasms. However, little is known about how LAT1 is associated with glucose metabolism, hypoxia and mammalian target of rapamycin (mTOR) signaling pathway in non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the relationship between LAT1 expression, and hypoxic marker and mTOR pathway in resected NSCLC. METHODS: One hundred and sixty patients were included in this study. Tumors sections were stained by immunohistochemistry for LAT1, glucose transporter 1 (Glut1), hypoxia inducible factor-1alpha (HIF-1alpha), hexokinase I, vascular endothelial growth factor (VEGF), microvessel density (MVD) by determinate by CD34, epidermal growth factor receptor (EGFR), Phosphatase and tensin analog (PTEN), phosph-Akt, phosph-mTOR and phosph-S6K. RESULTS: A positive LAT1 and CD98 expression were recognized in 36.8% (59/160) and 33.7% (54/160), respectively (p=0.640). LAT1 expression was significantly associated with CD98, hypoxic markers (Glut1, HIF-1alpha, hexokinase I, VEGF and CD34) and mTOR pathway (EGFR, a loss of PTEN, p-mTOR and p-S6K), especially in lung adenocarcinoma (AC). The expression profile of these biomarkers was significantly higher in non-AC than in AC, but almost these biomarkers were equally expressed between AC (n=16) and non-AC (n=43) patients with a positive LAT1 expression. Overexpression of LAT1 was closely associated with poor outcome in patient with AC. CONCLUSION: LAT1 expression is closely correlated with hypoxic markers and mTOR pathway in patients with resected NSCLC. PMID- 22046489 TI - The gold (III) porphyrin complex, gold-2a, suppresses WNT1 expression in breast cancer cells by enhancing the promoter association of YY1. AB - The gold (III) porphyrin complex, gold-2a, elicits anti-tumor activity by targeting the Wnt/beta-catenin signaling pathway [Chow KH et al, Cancer Research 2010;70(1):329-37]. Here, the molecular mechanisms underlying the inhibitory effects of this compound on WNT1 gene expression were elucidated further. A response element to gold-2a was identified located within the -1290 to -1112 nt region of the WNT1 promoter, containing a binding site for the transcription regulator Yin Yang 1 (YY1). Gold-2a promoted the association of YY1 and suppressor of zeste 12 (Suz12; a component of the polycomb repressor complex 2) with the WNT1 promoter. Under normal culture conditions, the intracellular translocalization of YY1 was synchronized with cell cycle progression and WNT1 expression. Gold-2a promoted the nuclear accumulation and abolished the nuclear exportation of YY1, resulting in a persistent inhibition of WNT1 expression and a cell cycle arrest at G1/S phase. A dimorphic role of YY1 in regulating cell proliferation and division was revealed. Thus, the present study extends the understanding of the anti-tumor mechanism of gold-2a to the epigenetic level, which involves the modulation of the dynamic interactions between YY1 and a specific region of the WNT1 promoter. PMID- 22046491 TI - TTF-1 positive small cell cancers: Don't think they're always primary pulmonary! AB - Thyroid transcription factor 1 (TTF-1) plays a key role in morphogenesis of the lungs and is expressed in up to 90% of pulmonary small cell carcinomas. This explains why this marker is frequently used in the search for the primary origin of metastatic endocrine tumours. Here we report on a TTF-1 expressing mixed endocrine-exocrine carcinoma of the common bile duct in a patient with pulmonary nodules that did not appear to be neoplastic. TTF-1 positivity in pulmonary and extrapulmonary neuroendocrine tumours is reviewed, and we conclude that TTF-1 expression in neuroendocrine tumours of the small-cell type are not uncommon at extrapulmonary locations. Therefore, immunohistochemistry for TTF-1 in such tumours should be interpreted with caution. PMID- 22046490 TI - Current status of robot-assisted gastric surgery. AB - In an effort to minimize the limitations of laparoscopy, a robotic surgery system was introduced, but its role for gastric cancer is still unclear. The objective of this article is to assess the current status of robotic surgery for gastric cancer and to predict future prospects. Although the current study was limited by its small number of patients and retrospective nature, robot-assisted gastrectomy with lymphadenectomy for the treatment of gastric cancer is a feasible and safe procedure for experienced laparoscopic surgeons. Most studies have reported satisfactory results for postoperative short-term coutcomes, such as: postoperative oral feeding, gas out, hospital stay and complications, compared with laparoscopic surgery; the difference is a longer operation time. However, robotic surgery showed a shallow learning curve compared with the familarity of conventional open surgery; after the accumulation of several cases, robotic surgery could be expected to result in a similar operation time. Robotic-assisted gastrectomy can expand the indications of minimally invasive surgery to include advanced gastric cancer by improving the ability to perform lymphadenectomy. Moreover, "total" robotic gastrectomy can be facilitated using a robot-sewing technique and gastric submucosal tumors near the gastroesophageal junction or pylorus can be resected safely by this novel technique. In conclusion, robot assisted gastrectomy may offer a good alternative to conventional open or laparoscopic surgery for gastric cancer, provided that long-term oncologic outcomes can be confirmed. PMID- 22046492 TI - Primary hepatic leiomyosarcoma: Case report and literature review. AB - Primary hepatic leiomyosarcoma are rare tumors with less than 30 cases reported in the English literature. Non specific presentations and often diagnosis delayed until they reach a large size, is the norm with therapy leading to an often dismal prognosis. A 67-year-old man presented complaining of abdominal pain and a palpable abdominal mass since Jan 2010. Abdominal ultrasonography and abdominal computed tomography revealed a large tumor in the left lobe of the liver. Surgical exploration was undertaken and an extended left hepatectomy with extension onto the dorsal part of segment 8 preserving the MHV with partial resection of segment 6 was undertaken. The weight of the resected specimen was 1300 g of the left lobectomy specimen and 8 g of the segment 6 partial resection specimen. The pathology report confirmed the diagnosis of leiomyosarcoma. On immunohistochemistry, the tumor cells were positive for smooth muscle actin stain. The patient is on regular follow up and is currently 9 mo post resection with no evidence of recurrence. We report the case of a resected primary hepatic leiomyosarcoma and emphasize the need for a global database for these rare tumors to promote a better and broader understanding of this less understood subject. PMID- 22046494 TI - Misinformation increases symptom reporting: a test - retest study. AB - OBJECTIVES: We examined whether misleading information (i.e. misinformation) may promote symptom reporting in non-clinical participants. DESIGN: A test-retest study in which we collected baseline data about participants' psychological symptoms and then misinformed them that they had rated two target symptoms relatively highly. During an interview, we determined whether participants would notice this misinformation and at direct and one-week follow-up, we evaluated whether the misinformation would exacerbate retest measures of the same symptoms. SETTING: A psychological laboratory. PARTICIPANTS: A total of 78 undergraduate students. MAIN OUTCOME MEASURES: Participants' scores on a widely used self report measure of psychological symptoms. RESULTS: We found that most participants (63%) were blind to the discrepancies between their original symptom ratings and the upgraded scores they were misinformed with. Furthermore, at the one-week follow-up retest, blind participants revised their symptom ratings in the direction of the misinformation (i.e. they increased their ratings of these symptoms). CONCLUSION: Introspective monitoring of common psychological symptoms is poor and this creates an opportunity for misinformation and symptom escalation. Our finding bears relevance to theories about the iatrogenic amplification of medically unexplained symptoms. PMID- 22046493 TI - Exploiting the P-1 pocket of BRCT domains toward a structure guided inhibitor design. AB - Breast cancer gene 1 carboxy terminus (BRCT) domains are found in a number of proteins that are important for DNA damage response (DDR). The BRCT domains bind phosphorylated proteins and these protein-protein interactions are essential for DDR and DNA repair. High affinity domain specific inhibitors are needed to facilitate the dissection of the protein-protein interactions in the DDR signaling. The BRCT domains of BRCA1 bind phosphorylated protein through a pSXXF consensus recognition motif. We identified a hydrophobic pocket at the P-1 position of the pSXXF binding site. Here we conducted a structure-guided synthesis of peptide analogs with hydrophobic functional groups at the P-1 position. Evaluation of these led to the identification of a peptide mimic 15 with a inhibitory constant (K(i)) of 40 nM for BRCT(BRCA1). Analysis of the TopBP1 and MDC1 BRCT domains suggests a similar approach is viable to design high affinity inhibitors. PMID- 22046495 TI - Patient and provider delays in breast cancer patients attending a tertiary care centre: a prospective study. AB - OBJECTIVES: To find out factors that are responsible for the patient or provider delays in the diagnosis of breast cancer in India. DESIGN: This prospective study was designed to be conducted over a period of two years including a cohort of 100 patients with locally advanced breast cancer. The delays were assessed using questionnaires prepared according to the Indian scenario. SETTING: A prospective study in an Indian setting. PARTICIPANTS: One hundred patients with locally advanced breast cancer receiving neoadjuvant chemotherapy were included after providing informed consent and receiving ethical committee clearance. MAIN OUTCOME MEASURES: The most common factor responsible for delays in diagnosis was observed to be the health providers, although illiteracy and lack of adequate healthcare services also contributed significantly. Unregistered medical practitioners or quacks contributed significantly to the delays in reporting and diagnosis of the disease. RESULTS: One hundred patients of locally advanced breast cancer were evaluated using standardized questionnaires to assess the delays in diagnosis. Provider delays were found to be significant (the unregistered doctors or quacks being a significant cause of delays).The average time lapse before diagnosis for rural patients was higher (67.5 days) compared to urban patients (53.7 days). The literacy levels of the patients also had a significant impact on the delays at diagnosis. The delay in illiterates was 60.6 days compared to 49.5 days for literates. CONCLUSIONS: The most common factor responsible for delays in reporting and diagnosis was observed to be at the end of the health providers, although illiteracy and lack of adequate healthcare services also contributed significantly. Unregistered medical practitioners or quacks contributed significantly to the delays in reporting and diagnosis of the disease. PMID- 22046496 TI - History of Medicine student selected components at UK medical schools: a questionnaire-based study. AB - OBJECTIVES: To determine the current status of History of Medicine student selected components (SSC) at UK medical schools. This includes the frequency, methods of delivery, assessment, and evaluation of such courses. DESIGN: An 18 item questionnaire was created, piloted, and then sent electronically in January 2010 to participants pertaining to their History of Medicine SSC provision as of 1 January 2010. Initial non-responders were re-sent the questionnaire in February 2010. SETTING: All UK medical schools. PARTICIPANTS: The History of Medicine SSC lead or overall SSC lead at each UK medical school were contacted to ascertain their History of Medicine SSC provision. MAIN OUTCOME MEASURES: Percentages of History of Medicine SSCs for each objective characteristic were obtained as well as general descriptive data. RESULTS: Fifteen of the 32 medical schools in the UK offer a History of Medicine SSC. Eleven medical schools (offering a total of 12 SSCs) completed the questionnaire (response rate 73.3%). Eight different teaching methods are used within the SSCs. Medical professionals most frequently deliver the teaching, which most frequently covers the 20th and 21st centuries. Four assessment methods are used among the SSCs, the most common being a group presentation. Questionnaires are the most frequent method of evaluation. There are several factors limiting the provision of some current SSCs, most commonly a lack of staff, teaching facilities, and available time within the curriculum. CONCLUSION: History of Medicine is being delivered more frequently in UK medical schools than when previously researched 40 years ago. However, the subject is still offered in a minority of the medical schools. This study offers useful information to consider for the development of current and potential new History of Medicine SSCs. PMID- 22046497 TI - Effective smoking cessation interventions for COPD patients: a review of the evidence. AB - OBJECTIVES: To review the effectiveness of smoking cessation interventions offered to chronic obstructive pulmonary disease (COPD) patients, and identify barriers to quitting experienced by them, so that a more effective service can be developed for this group. DESIGN: A rapid systematic literature review comprising computerized searches of electronic databases, hand searches and snowballing were used to identify both published and grey literature. SETTING: A review of studies undertaken in north-western Europe (defined as: United Kingdom, Ireland, France, Germany, Benelux and Nordic countries). PARTICIPANTS: COPD patients participating in studies looking at the effectiveness of smoking cessation interventions in this patient group, or exploring the barriers to quitting experienced by these patients. METHOD: Quantitative and qualitative papers were selected according to pre-specified inclusion and exclusion criteria, critically appraised, and quantitative papers scored against the NICE Levels of Evidence standardized hierarchy. MAIN OUTCOME MEASURE: Percentages of successful quitters and length of quit, assessed by self-report or biochemical analysis. Among qualitative studies, identified barriers to smoking cessation had to be explored. RESULTS: Three qualitative and 13 quantitative papers were finally selected. Effective interventions and barriers to smoking cessation were identified. Pharmacological support with Buproprion combined with counselling was significantly more efficacious in achieving prolonged abstinence than a placebo by 18.9% (95% CI 3.6 26.4%). Annual spirometry with a brief smoking cessation intervention, followed by a personal letter from a doctor, had a significantly higher >=1 year abstinence rate at three years among COPD patient smokers, compared to smokers with normal lung function (P < 0.001; z = 3.93). Identified barriers to cessation included: patient misinformation, levels of motivation, health beliefs, and poor communication with health professionals. CONCLUSION: Despite the public health significance of COPD, there is a lack of high-quality evidence showing which smoking cessation support methods work for these patients. This review describes three effective interventions, as well as predictors of quitting success that service providers could use to improve quit rates in this group. Areas that would benefit from urgent further research are also identified. PMID- 22046498 TI - Presenting a practical model for governmental political mapping on road traffic injuries in Iran in 2008: a qualitative study. AB - OBJECTIVES: This study was conducted to assess political mapping in relation to road traffic injuries (RTIs) management and prevention to present a practical model for RTIs. DESIGN: A phenomenological qualitative study was developed to identify stakeholders on RTI in Iran in 2008. SETTING: The designed questions were discussed by systematic discussion with the relevant specialists. After receiving written consent from the main responsible stakeholders, the questionnaire was filled in by trained experts. Themes were determined and content was analysed in each part. PARTICIPANTS: Main responsible stakeholders. MAIN OUTCOME MEASURES: By comparing other countries' political mappings which were found in the library and by Internet searching, political mapping of RTI in Iran was suggested. RESULTS: Subjects were 26 experts from governmental and non governmental organizations. The main proposed leading agencies were traffic police and presidency (13% each). Findings showed that only 31% of our political mapping was formed according to the World Health Organization (WHO). In 94% of cases, the involved organizations had unspecified roles; the reason was poor monitoring for RTI in 39% of organizations. Lack of adequate authority and suitable legislation, appropriate laws and tasks definition were 94% and 18%, respectively. The most essential policy to overcome problems was defined as appropriate legislation (21%), and the most frequent type of support needed was mentioned as adequate budgeting (25%). CONCLUSION: Traffic police can play the leading agency role by government support, with strong leadership, appropriate legislation, defined tasks and adequate budget. PMID- 22046499 TI - Disseminated mucocutaneous herpes simplex in an atopic individual. PMID- 22046500 TI - Primary care strategies to improve childhood immunisation uptake in developed countries: systematic review. AB - OBJECTIVES: To conduct a systematic review of strategies to optimize immunisation uptake within preschool children in developed countries. DESIGN: Systematic review. SETTING: Developed countries PARTICIPANTS: Preschool children who were due, or overdue, one or more of their routine primary immunisations. MAIN OUTCOME MEASURES: Increase in the proportion of the target population up to date with standard recommended universal vaccinations. RESULTS: Forty-six studies were included for analysis, published between 1980 and 2009. Twenty-six studies were randomized controlled trials, 11 were before and after trials, and nine were controlled intervention trials. Parental reminders showed a statistically significant increase in immunisation rates in 34% of included intervention arms. These effects were reported with both generic and specific reminders and with all methods of reminders and recall. Strategies aimed at immunisation providers were also shown to improve immunisation rates with a median change in immunisation rates of 7% when reminders were used, 8% when educational programmes were used and 19% when feedback programmes were used. CONCLUSION: General practitioners are uniquely positioned to influence parental decisions on childhood immunisation. A variety of strategies studied in primary care settings have been shown to improve immunisation rates, including parental and healthcare provider reminders. PMID- 22046501 TI - The potential role of oestrogens in relapse of recurrent affective psychosis. PMID- 22046503 TI - Pharmacogenetics and age-related macular degeneration. AB - Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical trials data continue to accumulate, these relationships may become more apparent. PMID- 22046502 TI - Current status of immunomodulatory and cellular therapies in preclinical and clinical islet transplantation. AB - Clinical islet transplantation is a beta-cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the beta-cells regenerative capacity of stem cells. PMID- 22046504 TI - New and old mechanisms associated with hypertension in the elderly. AB - Hypertension is a widely prevalent and important risk factor for cardiovascular diseases that increase with aging. The hallmark of hypertension in the elderly is increased vascular dysfunction. However, the molecular mechanisms by which increased blood pressure leads to vascular injury and impaired endothelial function are not well defined. In the present paper, we will analyze several mechanisms described in the scientific literature involved in hypertension in the elderly as endothelial dysfunction, increased oxygen delivery to tissues, inflammation, cellular apoptosis, and increased concentration of active metabolites. Also, we will focus on new molecular mechanisms involved in hypertension such as telomeres shortening, progenitor cells, circulating microparticles, and epigenetic factors that have appeared as possible causes of hypertension in the elderly. These molecular mechanisms may elucidate different origin for hypertension in the elderly and provide us with new targets for hypertension treatment. PMID- 22046505 TI - An Examination of Palliative or End-of-Life Care Education in Introductory Nursing Programs across Canada. AB - An investigation was done to assess for and describe the end-of-life education provided in Canadian nursing programs to prepare students for practice. All 35 university nursing schools/faculties were surveyed in 2004; 29 (82.9%) responded. At that time, all but one routinely provided this education, with that school developing a course (implemented the next year). As compared to past surveys, this survey revealed more class time, practicum hours, and topics covered, with this content and experiences deliberately planned and placed in curriculums. A check in 2010 revealed that all of these schools were providing death education similar to that described in 2004. These findings indicate that nurse educators recognize the need for all nurses to be prepared to care for dying persons and their families. Regardless, more needs to be done to ensure novice nurses feel capable of providing end-of-life care. Death education developments will be needed as deaths increase with population aging. PMID- 22046506 TI - MAP Kinases and Prostate Cancer. AB - The three major mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK are signal transducers involved in a broad range of cell functions including survival, apoptosis, and cell differentiation. Whereas JNK and p38 have been generally linked to cell death and tumor suppression, ERK plays a prominent role in cell survival and tumor promotion, in response to a broad range of stimuli such as cytokines, growth factors, ultraviolet radiation, hypoxia, or pharmacological compounds. However, there is a growing body of evidence supporting that JNK and p38 also contribute to the development of a number of malignances. In this paper we focus on the involvement of the MAPK pathways in prostate cancer, including the less-known ERK5 pathway, as pro- or antitumor mediators, through their effects on apoptosis, survival, metastatic potential, and androgen-independent growth. PMID- 22046507 TI - Neurospora crassa Light Signal Transduction Is Affected by ROS. AB - In the ascomycete fungus Neurospora crassa blue-violet light controls the expression of genes responsible for differentiation of reproductive structures, synthesis of secondary metabolites, and the circadian oscillator activity. A major photoreceptor in Neurospora cells is WCC, a heterodimeric complex formed by the PAS-domain-containing polypeptides WC-1 and WC-2, the products of genes white collar-1 and white collar-2. The photosignal transduction is started by photochemical activity of an excited FAD molecule noncovalently bound by the LOV domain (a specialized variant of the PAS domain). The presence of zinc fingers (the GATA-recognizing sequences) in both WC-1 and WC-2 proteins suggests that they might function as transcription factors. However, a critical analysis of the phototransduction mechanism considers the existence of residual light responses upon absence of WCC or its homologs in fungi. The data presented point at endogenous ROS generated by a photon stimulus as an alternative input to pass on light signals to downstream targets. PMID- 22046508 TI - Macrophage migration inhibitory factor: a multifunctional cytokine in rheumatic diseases. AB - Macrophage migration inhibitory factor (MIF) was originally identified in the culture medium of activated T lymphocytes as a soluble factor that inhibited the random migration of macrophages. MIF is now recognized to be a multipotent cytokine involved in the regulation of immune and inflammatory responses. Moreover, the pivotal nature of its involvement highlights the importance of MIF to the pathogenesis of various inflammatory disorders and suggests that blocking MIF may be a useful therapeutic strategy for treating these diseases. This paper discusses the function and expressional regulation of MIF in several rheumatic diseases and related conditions. PMID- 22046509 TI - Item Response Theory Analysis of Two Questionnaire Measures of Arthritis-Related Self-Efficacy Beliefs from Community-Based US Samples. AB - Using item response theory (IRT), we examined the Rheumatoid Arthritis Self efficacy scale (RASE) collected from a People with Arthritis Can Exercise RCT (346 participants) and 2 subscales of the Arthritis Self-efficacy scale (ASE) collected from an Active Living Every Day (ALED) RCT (354 participants) to determine which one better identifies low arthritis self-efficacy in community based adults with arthritis. The item parameters were estimated in Multilog using the graded response model. The 2 ASE subscales are adequately explained by one factor. There was evidence for 2 locally dependent item pairs; two items from these pairs were removed when we reran the model. The exploratory factor analysis results for RASE showed a multifactor solution which led to a 9-factor solution. In order to perform IRT analysis, one item from each of the 9 subfactors was selected. Both scales were effective at measuring a range of arthritis SE. PMID- 22046510 TI - Cutaneous polyarteritis nodosa in childhood: a case report and review of the literature. AB - Polyarteritis nodosa is a rare vasculitis of childhood. Cutaneous PAN (cPAN) is limited to the skin, muscles, joints, and peripheral nerves. We describe a 7.5 year-old girl with cPAN presenting initially as massive cervical edema who later went on to develop subcutaneous nodules, livedo reticularis, myositis, arthritis, and mononeuritis multiplex. The use of corticosteroids resulted in initial clinical improvement, but symptom recurrence necessitated disease modifying antirheumatic drugs and biologic therapy. We review a further 119 reports of biopsy proven cPAN in the literature. A majority of patients (96.6%) had cutaneous involvement; musculoskeletal involvement was common and included both articular (58.0%) and muscular (42.9%) symptoms, and nervous system involvement was least common (18.5%). Corticosteroids were used in the majority of patients (85.7%), followed by use of disease modifying antirheumatic drugs (33.0%), nonsteroidal anti-inflammatory drugs (10.7%), and intravenous immunoglobulin (9.8%). Therapy of cPAN with biologics has only been reported in 2 patients, and we report the first patient treated with Rituximab. A diagnosis of cPAN should be considered in a child with fever, vasculitic rash, and musculoskeletal symptoms. Most children respond to corticosteroids and have a benign course, but some require disease modifying antirheumatic drugs and biologic therapies. PMID- 22046511 TI - Staphylococcus aureus Decolonization Protocol Decreases Surgical Site Infections for Total Joint Replacement. AB - We investigated the effects of implementation of an institution-wide screening and decolonization protocol on the rates of deep surgical site infections (SSIs) in patients undergoing primary knee and hip arthroplasties. 2058 patients were enrolled in this study: 1644 patients in the treatment group and 414 in the control group. The treatment group attended preoperative admission testing (PAT) clinic where they were screened for MSSA and MRSA colonization. All patients were provided a 5-day course of nasal mupirocin and a single preoperative chlorhexidine shower. Additionally, patients colonized with MRSA received Vancomycin perioperative prophylaxis. The control group did not attend PAT nor receive mupirocin treatment and received either Ancef or Clindamycin for perioperative antibiotic prophylaxis. There were a total of 6 deep infections in the control group (1.45%) and 21 in the treatment group (1.28%); this represented a decrease of 13% (P = .809) in the treatment versus control group. This decrease represented a positive trend in favor of staphylococcus screening, decolonization with mupirocin, and perioperative Vancomycin for known MRSA carriers. PMID- 22046512 TI - Efficacy and effectiveness of exercise on tender points in adults with fibromyalgia: a meta-analysis of randomized controlled trials. AB - Fibromyalgia is a major public health problem affecting an estimated 200 to 400 million people worldwide. The purpose of this study was to use the meta-analytic approach to determine the efficacy and effectiveness of randomized controlled exercise intervention trials (aerobic, strength training, or both) on tender points (TPs) in adults with fibromyalgia. Using random effects models and 95% confidence intervals (CI), a statistically significant reduction in TPs was observed based on per-protocol analyses (8 studies representing 322 participants) but not intention-to-treat analyses (5 studies representing 338 participants) (per-protocol, g, -0.68, 95% CI, -1.16, -0.20; intention-to-treat, g, -0.24, 95% CI, -0.62, 0.15). Changes were equivalent to relative reductions of 10.9% and 6.9%, respectively, for per-protocol and intention-to-treat analyses. It was concluded that exercise is efficacious for reducing TPs in women with FM. However, a need exists for additional well-designed and reported studies on this topic. PMID- 22046513 TI - Adipokines and osteoarthritis: novel molecules involved in the pathogenesis and progression of disease. AB - Obesity has been considered a risk factor for osteoarthritis and it is usually accepted that obesity contributes to the development and progression of osteoarthritis by increasing mechanical load of the joints. Nevertheless, recent advances in the physiology of white adipose tissue evidenced that fat cells produce a plethora of factors, called adipokines, which have a critical role in the development of ostearthritis, besides to mechanical effects. In this paper, we review the role of adipokines and highlight the cellular and molecular mechanisms at play in osteoarthritis elicited by adipokines. We also emphasize how defining the role of adipokines has broadned our understanding of the diversity of factors involved in the genesis and progression of osteoarthritis in the hope of modifying it to prevent and treat diseases. PMID- 22046514 TI - An Eccentrically Biased Rehabilitation Program Early after TKA Surgery. AB - Rehabilitation services are less-studied aspects of the management following total knee arthroplasty (TKA) despite long-term suboptimal physical functioning and chronic deficits in muscle function. This paper describes the preliminary findings of a six-week (12 session) eccentrically-biased rehabilitation program targeted at deficits in physical function and muscle function, initiated one month following surgery. A quasiexperimental, one group, pretest-posttest study with thirteen individuals (6 female, 7 male; mean age 57 +/- 7 years) examined the effectiveness of an eccentrically-biased rehabilitation program. The program resulted in improvements in the primary physical function endpoints (SF-36 physical component summary and the six-minute walk test) with increases of 59% and 47%, respectively. Muscle function endpoints (knee extension strength and power) also increased 107% and 93%, respectively. Eccentrically-biased exercise used as an addition to rehabilitation may help amplify and accelerate physical function following TKA surgery. PMID- 22046515 TI - Coxarthritis as the presenting symptom of Gaucher disease type 1. AB - Gaucher disease (GD) type 1 is the most common lysosomal storage disorder due to beta glucocerebrosidase deficiency leading to an abnormal accumulation of its substrate, glucocerebroside, in the mononuclear phagocyte system. The disease presentation is usually characterized by signs and symptoms related to hypersplenism, such as splenomegaly, anaemia, thrombocytopenia and leucopenia. Skeletal disease may occur later for the infiltration of bone marrow by macrophages infiltration and bone resorption: bone involvement may be heterogeneously manifested by symptoms ranging from bone crisis to avascular necrosis, osteoporosis and defect in remodeling of long bones. Herein, we report a patient in whom the osteoarticular involvement has been the only symptom of the disease stressing that this unusual presentation of GD has prompted a wide differential diagnosis with more common forms of coxitis. PMID- 22046516 TI - Complementary and alternative exercises for management of osteoarthritis. AB - Osteoarthritis (OA) is a chronic condition characterized by degeneration of cartilage and its underlying bone within a joint. With no cure currently available, the goals of treating OA are to alleviate pain, maintain, or improve joint mobility, increase the muscle strength of the joints, and minimize the disabling effects of the disease. Recent research has suggested that complementary and alternative medicine (CAM) exercises may improve OA symptoms. This paper covers CAM mind-body exercises-Tai Chi, qigong, and yoga-for OA management and evaluates their benefits in pain reduction, muscle strength, physical function, stiffness, balance, fear of falling, self-efficacy, quality of life, and psychological outcomes in patients with OA, based on randomized controlled trials published. Findings from the literature suggest that CAM exercises demonstrate considerable promise in the management of OA. Future studies require rigorous randomized controlled trials with larger sample sizes. PMID- 22046517 TI - Current surgical treatment of knee osteoarthritis. AB - Osteoathritis (OA) of the knee is common, and the chances of suffering from OA increase with age. Its treatment should be initially nonoperative-and requires both pharmacological and nonpharmacological treatment modalities. If conservative therapy fails, surgery should be considered. Surgical treatments for knee OA include arthroscopy, cartilage repair, osteotomy, and knee arthroplasty. Determining which of these procedures is most appropriate depends on several factors, including the location, stage of OA, comorbidities on the one side and patients suffering on the other side. Arthroscopic lavage and debridement is often carried out, but does not alter disease progression. If OA is limited to one compartment, unicompartmental knee arthroplasty or unloading osteotomy can be considered. They are recommended in young and active patients in regard to the risks and limited durability of total knee replacement. Total arthroplasty of the knee is a common and safe method in the elderly patients with advanced knee OA. This paper summarizes current surgical treatment strategies for knee OA, with a focus on the latest developments, indications and level of evidence. PMID- 22046519 TI - The Influence of Radiographic Severity on the Relationship between Muscle Strength and Joint Loading in Obese Knee Osteoarthritis Patients. AB - Objective. To investigate the relationship between knee muscle strength and the external knee adduction moment during walking in obese knee osteoarthritis patients and whether disease severity influences this relationship. Methods. This cross-sectional study included 136 elderly obese (BMI > 30) adults with predominant medial knee osteoarthritis. Muscle strength, standing radiographic severity as measured by the Kellgren and Lawrence scale, and the peak external knee adduction moment were measured at self-selected walking speed. Results. According to radiographic severity, patients were classified as "less severe" (KL 1-2, N = 73) or "severe" (KL 3-4, N = 63). A significant positive association was demonstrated between the peak knee adduction moment and hamstring muscle strength in the whole cohort (P = .047). However, disease severity did not influence the relationship between muscle strength and dynamic medial knee joint loading. Severe patients had higher peak knee adduction moment and more varus malalignment (P < .001). Conclusion. Higher hamstring muscle strength relates to higher estimates of dynamic knee joint loading in the medial compartment. No such relationship existed for quadriceps muscle strength. Although cross sectional, the results suggest that hamstrings function should receive increased attention in future studies and treatments that aim at halting disease progression. PMID- 22046518 TI - Quantitative cartilage imaging in knee osteoarthritis. AB - Quantitative measures of cartilage morphology (i.e., thickness) represent potentially powerful surrogate endpoints in osteoarthritis (OA). These can be used to identify risk factors of structural disease progression and can facilitate the clinical efficacy testing of structure modifying drugs in OA. This paper focuses on quantitative imaging of articular cartilage morphology in the knee, and will specifically deal with different cartilage morphology outcome variables and regions of interest, the relative performance and relationship between cartilage morphology measures, reference values for MRI-based knee cartilage morphometry, imaging protocols for measurement of cartilage morphology (including those used in the Osteoarthritis Initiative), sensitivity to change observed in knee OA, spatial patterns of cartilage loss as derived by subregional analysis, comparison of MRI changes with radiographic changes, risk factors of MRI-based cartilage loss in knee OA, the correlation of MRI-based cartilage loss with clinical outcomes, treatment response in knee OA, and future directions of the field. PMID- 22046520 TI - Serum leptin concentration positively correlates with body weight and total fat mass in postmenopausal Japanese women with osteoarthritis of the knee. AB - The objective of the present study was to identify factors correlated with the serum leptin concentration in women with knee OA. Fifty postmenopausal Japanese women with knee OA (age: 50-88 years) were recruited in our outpatient clinic. Plain radiographs of the knee were taken, and urine and blood samples were collected. Dual-energy X-ray absorptiometry (DXA) scanning was performed for the whole body and lumbar spine, and factors correlated with the serum leptin concentration were identified. A simple linear regression analysis showed that body weight, body mass index, whole-body bone mineral density (BMD), total fat mass, and total fat percentage, but not age, height, lumbar spine BMD, lean body mass, serum and urinary bone turnover markers, or the radiographic grade of knee OA, were significantly correlated with the serum leptin concentration. A multiple regression analysis showed that among these factors, only body weight and total fat mass exhibited a significant positive correlation with the serum leptin concentration. These results suggest that the serum leptin concentration might be related to increases in body weight and total fat mass, but not to BMD or bone turnover markers, in postmenopausal women with OA. PMID- 22046521 TI - The self-administered patient satisfaction scale for primary hip and knee arthroplasty. AB - Introduction. The objective of this study was to develop a short self-report questionnaire for evaluating patient satisfaction with the outcome of hip and knee replacement surgery. Methods. This scale consists of four items focusing on satisfaction with the extent of pain relief, improvement in ability to perform home or yard work, ability to perform recreational activities, and overall satisfaction with joint replacement. This instrument does not measure satisfaction with process of care. The responses are scored on a Likert scale, with the total score ranging from 25 to 100 per question. The instrument was tested on 1700 patients undergoing primary total hip and total knee replacement surgery, evaluated preoperatively, at 12 weeks, and one year postoperatively. Psychometric testing included internal consistency, measured with Cronbach's alpha, and convergent validity, measured by correlation with changes in measures of health status between the preoperative, 12-week, and one-year evaluations. Results. The internal consistency (reliability) of the scale, measured by the Cronbach's alpha, ranged from 0.86 to 0.92. The scale demonstrated substantial ceiling effects at 1 year. The scale scores correlated modestly with the absolute SF-36 PCS and WOMAC scores (rho = 0.56-0.63 and also with the WOMAC change scores (rho = 0.38-0.46) at both 12-week and 1-year followups. Conclusions. This instrument is valid and reliable for measuring patient satisfaction following primary hip and knee arthroplasty and could be further evaluated for use with other musculoskeletal interventions. PMID- 22046523 TI - Rheumatoid factor and its interference with cytokine measurements: problems and solutions. AB - Use of cytokines as biomarkers for disease is getting more widespread. Cytokines are conveniently determined by immunoassay, but interference from present antibodies is known to cause problems. In rheumatoid arthritis (RA), interference of rheumatoid factor (RF) may be problematic. RF covers a group of autoantibodies from immunoglobulin subclasses and is present in 65-80% of RA patients. Partly removal of RF is possible by precipitation. This study aims at determining the effects of presence of RF in blood and synovial fluid on cytokine measurements in samples from RA patients and finding possible solutions for recognized problems. IL-1beta, IL-4, IL-6, and IL-8 were determined with multiplex immunoassays (MIA) in samples from RA patients prior to and after polyethylene glycol (PEG 6000) precipitation. Presence of RF does interfere with MIA. PEG 6000 precipitation abolishes this RF interference. We recommend PEG precipitation for all immunoassay measurements of plasma samples from RA patients. PMID- 22046522 TI - Developmental mechanisms in articular cartilage degradation in osteoarthritis. AB - Osteoarthritis is the most common arthritic condition, which involves progressive degeneration of articular cartilage. The most recent accomplishments have significantly advanced our understanding on the mechanisms of the disease development and progression. The most intriguing is the growing evidence indicating that extracellular matrix destruction in osteoarthritic articular cartilage resembles that in the hypertrophic zone of fetal growth plate during endochondral ossification. This suggests common regulatory mechanisms of matrix degradation in OA and in the development and can provide new approaches for the treatment of the disease by targeting reparation of chondrocyte phenotype. PMID- 22046524 TI - Popliteal cysts in paediatric patients: clinical characteristics and imaging features on ultrasound and MRI. AB - Popliteal cysts, or Baker cysts, are considered rare in children and may exhibit particular features, as compared with adults. We studied data from 80 paediatric patients with 55 Baker cysts, examined over a period of 7 years, and correlated clinical presentation with findings on ultrasonography and MRI. Prevalence of popliteal cysts was 57% in arthritic knees, 58% with hypermobility syndrome, and 28% without risk factors. Only one patient had a trauma history and showed an ipsilateral cyst. Mean cyst volume was 3.4 mL; cysts were larger in boys. Patients with arthritis had echogenic cysts in 53%. Cyst communication with the joint space was seen in 64% on ultrasonography and 86% on MRI. In conclusion, Baker cysts are a common finding in a clinically preselected paediatric population. Children with Baker cysts should be assessed for underlying arthritis and inherited joint hypermobility, while sporadic Baker cysts appear to be common, as well. PMID- 22046525 TI - The roles of interleukin-6 in the pathogenesis of rheumatoid arthritis. AB - Several clinical studies have demonstrated that the humanized anti-interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) improves clinical symptoms and prevents progression of joint destruction in rheumatoid arthritis (RA). However, the precise mechanism by which IL-6 blockade leads to the improvement of RA is not well understood. IL-6 promotes synovitis by inducing neovascularization, infiltration of inflammatory cells, and synovial hyperplasia. IL-6 causes bone resorption by inducing osteoclast formation via the induction of RANKL in synovial cells, and cartilage degeneration by producing matrix metalloproteinases (MMPs) in synovial cells and chondrocytes. Moreover, IL-6 is involved in autoimmunity by altering the balance between T(h)17 cells and T(reg). IL-6 also acts on changing lipid concentrations in blood and on inducing the production of hepcidin which causes iron-deficient anemia. In conclusion, IL-6 is a major player in the pathogenesis of RA, and current evidence indicates that the blockade of IL-6 is a beneficial therapy for RA patients. PMID- 22046526 TI - Patella Eversion Reduces Early Knee Range of Motion and Muscle Torque Recovery after Total Knee Arthroplasty: Comparison between Minimally Invasive Total Knee Arthroplasty and Conventional Total Knee Arthroplasty. AB - We hypothesized that patella eversion during total knee arthroplasty (TKA) reduces early return of active knee extension and flexion, quadriceps muscle strength, and postoperative pain. In 100 conventional TKA knees and 100 minimally invasive TKA (MIS TKA) knees, we compared knee range of motion (ROM), postoperative pain, and quadriceps muscle strength at 1 day, 4 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 12 weeks, 1 year, and 5 years after surgery. The differences of surgical approach between MIS TKA and conventional TKA of this study are length of skin incision with subcutaneal flap and patella eversion. In MIS TKA, skin incision is shorter than conventional TKA. Furthermore, patella is not everted in MIS TKA procedure. There were no significant differences in preoperative factors. Postoperative improvement of ROM, postoperative muscle strength recovery, and postoperative improvement of visual analog scale were faster in patients with MIS TKA when compared to that in patients with conventional TKA. On the other hand, no significant difference was observed in complication, 5-year clinical results of subjective knee function score, and the postoperative component angle and lower leg alignment. These results indicate that patella eversion may affect muscle strength recovery and postoperative pain. PMID- 22046528 TI - Correlation between Oxidative Stress and Thyroid Function in Patients with Nephrotic Syndrome. AB - Background. The present study is to look for a correlation between oxidative stress and thyroid function in patients with the nephrotic syndrome in the remission phase as well as in a persistent proteinuric state. Introduction. Nephrotic syndrome is a form of chronic kidney disease due to which blood loses protein through the urine. We wanted to know if there was an increased loss of thyroid hormones in urine affecting thyroid function. Methods. 60 patients with nephrotic syndrome and 20 healthy non-proteinuric individuals as control subjects were enrolled in the study. We measured their serum tri-iodothyronine, thyroxine and thyroid-stimulating hormone. Estimation of lipid peroxidation (LPx) catalase, superoxide dismutase (SOD), and Glutathione peroxidase (GPx) were carried out by standard methods. Results. TSH was elevated in the nephrotic patients compared to controls, while TT4 and TT3 were significantly lower in the patients than in controls. Lipid Peroxidation and GPx were significantly higher in the nephrotic syndrome patients than in the controls, while SOD and catalase were significantly lower than in patients than in the control subjects. Conclusion. Nephrotic patients can lose significant amounts of thyroid hormones along with protein in urine, which can affect thyroid status, but this is reversible on remission. PMID- 22046529 TI - Cancer, senescence, and aging: translation from basic research to clinics. PMID- 22046531 TI - Accuracy of D-Dimers to Rule Out Venous Thromboembolism Events across Age Categories. AB - Background. Strategies combining pretest clinical assessment and D-dimers measurement efficiently and safely rule out venous thromboembolism events (VTE) in low- and intermediate-risk patients. Objectives. As process of ageing is associated with altered concentrations of coagulation markers including an increase in D-dimers levels, we investigated whether D-dimers could reliably rule out VTE across age categories. Method. We prospectively assessed the test performance in 1,004 patients visiting the emergency department during the 6 month period with low or intermediate risk of VTE who also received additional diagnostic procedures. Results. 67 patients had VTE with D-dimers levels above the threshold, and 3 patients displayed D-dimers levels below the threshold. We observed that specificity of D-dimers test decreased in an age-dependent manner. However, sensitivity and negative predictive value remained at very high level in each age category including older patients. Conclusion. We conclude that, even though D-dimers level could provide numerous false positive results in elderly patients, its high sensitivity could reliably help physicians to exclude the diagnosis of VTE in every low- and intermediate-risk patient. PMID- 22046530 TI - Shorter leukocyte telomere length in midlife women with poor sleep quality. AB - Background. Accumulating evidence supports leukocyte telomere length (LTL) as a biological marker of cellular aging. Poor sleep is a risk factor for age-related disease; however, the extent to which sleep accounts for variation in LTL is unknown. Methods. The present study examined associations of self-reported sleep duration, onset latency, and subjective quality with LTL in a community-dwelling sample of 245 healthy women in midlife (aged 49-66 years). Results. While sleep duration and onset latency were unrelated to LTL, women reporting poorer sleep quality displayed shorter LTL (r = 0.14, P = 0.03), independent of age, BMI, race, and income (b = 55.48, SE = 27.43, P = 0.04). When analyses were restricted to participants for whom sleep patterns were chronic, poorer sleep quality predicted shorter LTL independent of covariates and perceived psychological stress. Conclusions. This study provides the first evidence that poor sleep quality explains significant variation in LTL, a marker of cellular aging. PMID- 22046527 TI - Biomechanical influence of cartilage homeostasis in health and disease. AB - There is an urgent demand for long term solutions to improve osteoarthritis treatments in the ageing population. There are drugs that control the pain but none that stop the progression of the disease in a safe and efficient way. Increased intervention efforts, augmented by early diagnosis and integrated biophysical therapies are therefore needed. Unfortunately, progress has been hampered due to the wide variety of experimental models which examine the effect of mechanical stimuli and inflammatory mediators on signal transduction pathways. Our understanding of the early mechanopathophysiology is poor, particularly the way in which mechanical stimuli influences cell function and regulates matrix synthesis. This makes it difficult to identify reliable targets and design new therapies. In addition, the effect of mechanical loading on matrix turnover is dependent on the nature of the mechanical stimulus. Accumulating evidence suggests that moderate mechanical loading helps to maintain cartilage integrity with a low turnover of matrix constituents. In contrast, nonphysiological mechanical signals are associated with increased cartilage damage and degenerative changes. This review will discuss the pathways regulated by compressive loading regimes and inflammatory signals in animal and in vitro 3D models. Identification of the chondroprotective pathways will reveal novel targets for osteoarthritis treatments. PMID- 22046532 TI - Ambulance Crash Characteristics in the US Defined by the Popular Press: A Retrospective Analysis. AB - Ambulance crashes are a significant risk to prehospital care providers, the patients they are carrying, persons in other vehicles, and pedestrians. No uniform national transportation or medical database captures all ambulance crashes in the United States. A website captures many significant ambulance crashes by collecting reports in the popular media (the website is mentioned in the introduction). This report summaries findings from ambulance crashes for the time period of May 1, 2007 to April 30, 2009. Of the 466 crashes examined, 358 resulted in injuries to prehospital personnel, other vehicle occupants, patients being transported in the ambulance, or pedestrians. A total of 982 persons were injured as a result of ambulance crashes during the time period. Prehospital personnel were the most likely to be injured. Provider safety can and should be improved by ambulance vehicle redesign and the development of improved occupant safety restraints. Seventy-nine (79) crashes resulted in fatalities to some member of the same groups listed above. A total of 99 persons were killed in ambulance crashes during the time period. Persons in other vehicles involved in collisions with ambulances were the most likely to die as a result of crashes. In the urban environment, intersections are a particularly dangerous place for ambulances. PMID- 22046533 TI - Difficult Airway Management Algorithm in Emergency Medicine: Do Not Struggle against the Patient, Just Skip to Next Step. AB - We report a case of prehospital "cannot intubate" and "cannot ventilate" scenarios successfully managed by strictly following a difficult airway management algorithm. Five airway devices were used: the Macintosh laryngoscope, the gum elastic Eschmann bougie, the LMA Fastrach, the Melker cricothyrotomy cannula, and the flexible fiberscope. Although several airway devices were used, overall airway management duration was relatively short, at 20 min, because for each scenario, failed primary and secondary backup devices were quickly abandoned after 2 failed attempts, each attempt of no more than 2 min in duration, in favor of the tertiary rescue device. Equally, all three of these rescue devices failed, an uncuffed cricothyroidotomy cannula was inserted to restore optimal arterial oxygenation until a definitive airway was secured in the ICU using a flexible fiberscope. Our case reinforces the need to strictly follow a difficult airway management algorithm that employs a limited number of effective devices and techniques, and highlights the imperative for early activation of successive preplanned steps of the algorithm. PMID- 22046534 TI - Wenckebach Block due to Hyperkalemia: A Case Report. AB - Hyperkalemia is a commonly encountered electrolyte abnormality that can significantly alter normal cardiac conduction. Potentially lethal dysrhythmias associated with hyperkalemia include complete heart block and Mobitz Type II second-degree AV block. We report a unique case of Mobitz Type 1 second-degree atrioventricular (AV) block, known commonly as Wenckebach, due to hyperkalemia. The patient's symptoms and electrocardiogram (ECG) evidence of Wenckebach block resolved with lowering of serum potassium levels, with subsequent ECG showing first-degree AV block. This paper highlights an infrequently reported dysrhythmia associated with hyperkalemia that emergency physicians should be familiar with. PMID- 22046535 TI - A Patient with Splenic Artery Aneurysm Rupture and the Importance of Rapid Sonography in the ED. AB - We report a case of a splenic artery aneurysm rupture presenting with shock which required timely embolization therapy. This case demonstrates how the rapid use of bedside ultrasound by emergency department (ED) physicians can help identify the cause of shock and, therefore, initiate appropriate treatment quickly even if the cause is rare, as in this case. PMID- 22046536 TI - The emergency management and treatment of severe burns. AB - Burn injuries continue to cause morbidity and mortality internationally. Despite international collaborations and preventative measures, there are still many cases reported in high- and low-income countries. The treatment of these patients is often protracted and requires extensive resources. The adequate resuscitation of these patients coupled with meticulous wound care can have a huge impact on their outcome. The authors present a simple guideline for the initial management of severe burns which is utilised by the South African Burn Society and is based on the guidelines of the American Burn Association and the Australian and New Zealand Burn Association. PMID- 22046537 TI - Expectations of Care, Perceived Safety, and Anxiety following Acute Behavioural Disturbance in the Emergency Department. AB - Objective. We explored perspectives of emergency department users (patients and visitors) regarding the management of acute behavioural disturbances in the emergency department and whether these disturbances influenced their levels of anxiety. Methods. Emergency department patients and visitors were surveyed using the State-Trait Anxiety Inventory, and a purpose-designed questionnaire and semistructured interview. The main outcome measures were themes that emerged from the questionnaires, the interviews, and scores from the state component of the State-Trait Anxiety Inventory. Results. 70 participants were recruited. Users of the emergency department preferred behaviourally disturbed people be managed in a separate area from the general emergency department population so that the disturbance was inaudible (n = 32) and out of view (n = 40). The state anxiety levels of those that witnessed an acute behavioural disturbance were within the normal range and did not differ to that of ED patients that were not present during such a disturbance (median, control = 37, Code Grey = 33). Conclusions. Behavioural disturbances in the emergency department do not provoke anxiety in other users. However, there is a preference that such disturbances be managed out of visual and audible range. Innovative design features may be required to achieve this. PMID- 22046538 TI - Micropower impulse radar: a novel technology for rapid, real-time detection of pneumothorax. AB - Pneumothorax detection in emergency situations must be rapid and at the point of care. Current standards for detection of a pneumothorax are supine chest X-rays, ultrasound, and CT scans. Unfortunately these tools and the personnel necessary for their facile utilization may not be readily available in acute circumstances, particularly those which occur in the pre-hospital setting. The decision to treat therefore, is often made without adequate information. In this report, we describe a novel hand-held device that utilizes Micropower Impulse Radar to reliably detect the presence of a pneumothorax. The technology employs ultra wide band pulses over a frequency range of 500 MHz to 6 GHz and a proprietary algorithm analyzes return echoes to determine if a pneumothorax is present with no user interpretation required. The device has been evaluated in both trauma and surgical environments with sensitivity of 93% and specificity of 85%. It is has the CE Mark and is available for sale in Europe. Post market studies are planned starting in May of 2011. Clinical studies to support the FDA submission will be completed in the first quarter of 2012. PMID- 22046539 TI - Improved survival with therapeutic hypothermia after cardiac arrest with cold saline and surfacing cooling: keep it simple. AB - Aim. To evaluate whether the introduction of a therapeutic hypothermia (TH) protocol consisting of cold saline infusion and surface cooling would be effective in targeting mild therapeutic hypothermia (32-34 degrees C). Additionally, to evaluate if TH would improve survival after cardiac arrest. Design. Before-after design. Setting. General Intensive Care Unit (ICU) at an urban general hospital with 470 beds. Patients and Methods. Patients admitted in the ICU after cardiac arrest between 2004 and 2009 were included. Effectiveness of the TH protocol to achieve the targeted temperature was evaluated. Hospital mortality was compared before (October 2004-March 2006) and after (April 2006 September 2009) the protocol implementation. Results. Hundred and thirty patients were included, 75 patients were not submitted to TH (before TH group), and 55 were submitted to TH (TH group). There were no significant differences concerning baseline, ICU, and cardiac arrest characteristics between both groups. There was a significant reduction in hospital mortality from 61% (n = 46) in the before TH group to 40% (n = 22) in the TH group. Conclusion. Our protocol consisting of cold saline infusion and surface cooling might be effective in inducing and maintaining mild therapeutic hypothermia. TH achieved with this protocol was associated with a significant reduction in hospital mortality. PMID- 22046540 TI - A brief training module improves recognition of echocardiographic wall-motion abnormalities by emergency medicine physicians. AB - Objective. Wall-motion abnormality on echocardiogram is more sensitive in detecting cardiac ischemia than the electrocardiogram, but the use of bedside echocardiography by emergency physicians (EPs) for this purpose does not appear to be widespread, apparently due to limited data on proficiency of EPs for this task. We sought to determine the effect of a brief training module on the ability of EPs to recognize wall motion abnormalities on echocardiograms. Methods. We developed a brief training and testing module and presented it to EPs. After baseline testing of 15 echocardiograms, we presented the 30-minute training module, and administered a new test of 15 different echocardiograms. Physicians were asked to interpret the wall motion as normal or abnormal. Results. 35 EPs over two separate sessions showed significant improvement recognition of wall motion abnormalities after the brief training module. Median score on the baseline test was 67%, interquartile range (IQR) 53% to 80%, while the median score on the posttraining test was 87%, IQR 80% to 87%, P < .001, independent of time in practice or prior training. Conclusion. With only brief training on how to recognize wall motion abnormalities on echocardiograms, EPs showed significant improvement in ability to identify wall motion abnormalities. PMID- 22046541 TI - Is blood alcohol level a good predictor for injury severity outcomes in motor vehicle crash victims? AB - Experimental studies in animals suggest that alcohol may influence pathophysiologic response to injury mechanisms. However, biological evidence for the alcohol-injury severity relationship provides conflicting results. The purpose of our retrospective cross-sectional study in 2,323 people was to assess whether blood alcohol level (BAC) adversely influences injury severity in victims of motor vehicle collisions (MVCs). We found no difference in mortality OR 1.09 (0.73-1.62), or length of hospital stay, and a trend for lower ISS score was found in the high-alcohol group (P = 0.052). Furthermore, the high-alcohol group demonstrated a lower adjusted rate of severe head injury OR 0.65 (0.48-0.87), chest injury OR 0.58 (0.42-0.80), and serious extremity injury OR 0.10 (0.01 0.76). The findings of our study do not demonstrate a dose-response relationship between alcohol consumption and injury severity in MVCs. This study implies that higher BAC may lead to less severe injuries, without impacting mortality or length of hospital stay, however, further research is required to elucidate the nature of this relationship. PMID- 22046542 TI - Incidental Findings on CT Scans in the Emergency Department. AB - Objectives. Incidental findings on computed tomography (CT) scans are common. We sought to examine rates of findings and disclosure among discharged patients who received a CT scan in the ED. Methods. Retrospective chart review (Aug-Oct 2009) of 600 patients age 18 and older discharged home from an urban Level 1 trauma center. CT reports were used to identify incidental findings and discharge paperwork was used to determine whether the patient was informed of these findings. Results. There were 682 CT scans among 600 patients: 199 Abdomen & Pelvis, 405 Head, and 78 Thorax. A total of 348 incidental findings were documented in 228/682 (33.4%) of the scans, of which 34 (9.8%) were reported to patients in discharge paperwork. Patients with 1 incidental finding were less likely to receive disclosure than patients with 2 or more (P = .010). Patients age <60 were less likely to have incidental findings (P < .001). There was no significant disclosure or incidental finding difference by gender. Conclusions. While previous research suggests that CT incidental findings are often benign, reporting to patients is recommended but this is rarely happening. PMID- 22046543 TI - Seatbelt injury causing small bowel devascularisation: case series and review of the literature. AB - The use of seatbelts has increased significantly in the last twenty years, leading to a decrease in mortality from road traffic accidents (RTA). However, this increase in seatbelt use has also led to a change in the spectrum of injuries from RTA; abdominal injuries, particularly intestinal injuries have dramatically increased with the routine use of seatbelts. Such intestinal injuries frequently result from improper placement of the "lap belt". We present 3 cases in which passengers wearing a seatbelt sustained significant devascularisation injuries to the small bowel requiring emergency surgical intervention. A high index of suspicion is crucial in such cases to prevent delays in diagnosis that can lead to severe complications and adverse outcomes. It is evident that while advocating seatbelt use, the importance of education in correct seatbelt placement should also be a focus of public health strategies to reduce RTA morbidity and mortality. PMID- 22046544 TI - Diffusion of cardiopulmonary resuscitation training to chinese immigrants with limited english proficiency. AB - Cardiopulmonary resuscitation (CPR) is an effective intervention for prehospital cardiac arrest. Despite all available training opportunities for CPR, disparities exist in participation in CPR training, CPR knowledge, and receipt of bystander CPR for certain ethnic groups. We conducted five focus groups with Chinese immigrants who self-reported limited English proficiency (LEP). A bilingual facilitator conducted all the sessions. All discussions were taped, recorded, translated, and transcribed. Transcripts were analyzed by content analysis guided by the theory of diffusion. The majority of participants did not know of CPR and did not know where to get trained. Complexity of CPR procedure, advantages of calling 9-1-1, lack of confidence, and possible liability discourage LEP individuals to learn CPR. LEP individuals welcome simplified Hands-Only CPR and are willing to perform CPR with instruction from 9-1-1 operators. Expanding the current training to include Hands-Only CPR and dispatcher-assisted CPR may motivate Chinese LEP individuals to get trained for CPR. PMID- 22046545 TI - Isolated transverse sacrum fracture: a case report. AB - Sacral fracture commonly results from high-energy trauma. Most insufficiency fractures of the sacrum are seen in women after the age of 70. Fractures of the sacrum are rare and generally combined with a concomitant pelvic fracture. Transverse sacral fractures are even less frequent which constitute only 3-5% of all sacral fractures. This type of fractures provide a diagnostic challenge. We report a unique case of isolated transverse fracture of sacrum in a young man sustained low-energy trauma. The patient presented to our emergency department after several hours of injury, and diagnosed by clinical features and roentgenogram findings. PMID- 22046546 TI - Vascular injury accompanying displaced proximal humeral fractures: two cases and a review of the literature. AB - We present two cases in which displaced proximal humeral fractures are accompanied by vascular injury. These Injuries are very rare but severe and the accompanying vascular impairment can have great clinical consequences. Therefore, we try to emphasize on the importance of thorough and accurate diagnostics, because it is obligatory for early diagnosis and improving the eventual outcome of these injuries. The specific order in treatment (internal fixation first or vascular repair first) depends on the severity of the accompanying vascular injury. The increasing use of endovascular procedures to treat vascular lesions is a very interesting development with several advantages, especially in elderly and multimorbid patients. PMID- 22046547 TI - Demographic analysis of emergency department patients at the ruijin hospital, shanghai. AB - Emergency medicine is an upcoming discipline that is still under development in many countries. Therefore, it is important to gain insight into the organization and patients presenting to the Emergency Department (ED). The aim of this cross sectional study was to provide an epidemiological description of complaints and referrals of the patients visiting the ED of the Ruijin Hospital in Shanghai, China. A questionnaire was developed and completed for a convenience sample of all patients presenting to the Triage Desk of the ED. The study was performed in June 2008. A total of 2183 questionnaires were completed. The most common complaints were fever (15%), stomach/abdominal pain (15%), vertigo/dizziness (11%), and cough (10%). Following triage, patients were predominantly referred to an internist (41%), neurologist (14%), pulmonologist (11%), or general surgeon (9%). This study provides a better understanding of the reason for the ED visit and the triage system at the ED of the Ruijin Hospital. The results can be used in order to improve facilities appropriate for the specific population in the ED. PMID- 22046548 TI - Lunar tractive forces and renal stone incidence. AB - Background. Several factors are implicated in renal stone formation and peak incidence of renal colic admissions to emergency departments (ED). Little is known about the influence of potential environmental triggers such as lunar gravitational forces. We conducted a retrospective study to test the hypothesis that the incidence of symptomatic renal colics increases at the time of the full and new moon because of increased lunar gravitational forces. Methods. We analysed 1500 patients who attended our ED between 2000 and 2010 because of nephrolithiasis-induced renal colic. The lunar phases were defined as full moon +/- 1 day, new moon +/- 1 day, and the days in-between as "normal" days. Results. During this 11-year period, 156 cases of acute nephrolithiasis were diagnosed at the time of a full moon and 146 at the time of a new moon (mean of 0.4 per day for both). 1198 cases were diagnosed on "normal" days (mean 0.4 per day). The incidence of nephrolithiasis in peak and other lunar gravitational phases, the circannual variation and the gender-specific analysis showed no statistically significant differences. Conclusion. In this adequate powered longitudinal study, changes in tractive force during the different lunar phases did not influence the incidence of renal colic admissions in emergency department. PMID- 22046549 TI - Blunt cardiac injury in trauma patients with thoracic aortic injury. AB - Trauma patients with thoracic aortic injury (TAI) suffer blunt cardiac injury (BCI) at variable frequencies. This investigation aimed to determine the frequency of BCI in trauma patients with TAI and compare with those without TAI. All trauma patients with TAI who had admission electrocardiography (ECG) and serum creatine kinase-MB (CK-MB) from January 1999 to May 2009 were included as a study group at a level I trauma center. BCI was diagnosed if there was a positive ECG with either an elevated CK-MB or abnormal echocardiography. There were 26 patients (19 men, mean age 45.1 years, mean ISS 34.4) in the study group; 20 had evidence of BCI. Of 52 patients in the control group (38 men, mean age 46.9 years, mean ISS 38.7), eighteen had evidence of BCI. There was a significantly higher rate of BCI in trauma patients with TAI versus those without TAI (77% versus 35%, P < 0.001). PMID- 22046550 TI - The role of thrombelastography in multiple trauma. AB - Hemorrhage and traumatic coagulopathyis are major causes of early death in multiply injured patients. Thrombelastography (TEG) seems to be a fast and accurate coagulation test in trauma care. We suggest that multiply injured trauma patients would benefit the most from an early assessment of coagulation by TEG, mainly RapidTEG, to detect an acute traumatic coagulopathy and especially primary fibrinolysis, which is related with high mortality. This review gives an overview on TEG and its clinical applications. PMID- 22046551 TI - Impact of 2004 tsunami in the islands of Indian ocean: lessons learned. AB - Tsunami of 2004, caused by a 9.0 magnitude earthquake, is the most devastating tsunami in modern times, affecting 18 countries in Southeast Asia and Southern Africa, killing more than 250,000 people in a single day, and leaving more than 1.7 million homeless. However, less reported, albeit real, is its impact in the islands of the Indian Ocean more than 1,000 miles away from its epicenter. This is the first peer-reviewed paper on the 2004 tsunami events specifically in the eleven nations bordering the Indian Ocean, as they constitute a region at risk, due to the presence of tectonic interactive plate, absence of a tsunami warning system in the Indian Ocean, and lack established communication network providing timely information to that region. Our paper has a dual objective: the first objective is to report the 2004 tsunami event in relation to the 11 nations bordering the Indian Ocean. The second one is to elaborate on lessons learned from it from national, regional, and international disaster management programs to prevent such devastating consequences of tsunami from occurring again in the future. PMID- 22046552 TI - Skull base osteomyelitis in the emergency department: a case report. AB - Skull base osteomyelitis (SBO) is a rare clinical presentation and usually occurs as a complication of trauma or sinusitis. A 5-year-old child presented to the emergency department with a three-week history of fever associated with drowsiness and left parietal headache, and a week's history of swelling on the left frontoparietal soft tissue. He had suffered a penetrating scalp injury four month ago. On physical examination, there was a tender swelling with purulent stream on the lateral half of his scalp. His vital signs are within normal limits. Plain X-ray of the skull showed a lytic lesion on the left frontoparietal bone. A cranial computed tomography (CT) scan demonstrated a large subgaleal abscess at the left frontoparietal region. SBO possesses a high morbidity and mortality; therefore, prompt diagnosis and appropriate treatment are mandatory to prevent further complications and to reduce morbidity and mortality significantly. PMID- 22046553 TI - Perceived differences in the management of mental health patients in remote and rural australia and strategies for improvement: findings from a national qualitative study of emergency clinicians. AB - Introduction. We aimed to describe perceptions of Australian emergency clinicians of differences in management of mental health patients in rural and remote Australia compared with metropolitan hospitals, and what could be improved. Methods. Descriptive exploratory study using semi-structured telephone interviews of doctors and nurses in Australian emergency departments (EDs), stratified to represent states and territories and rural or metropolitan location. Content analysis of responses developed themes and sub-themes. Results. Of 39 doctors and 32 nurses responding to email invitation, 20 doctors and 16 nurses were interviewed. Major themes were resources/environment, staff and patient issues. Clinicians noted lack of access in rural areas to psychiatric support services, especially alcohol and drug services, limited referral options, and a lack of knowledge, understanding and acceptance of mental health issues. The clinicians suggested resource, education and guideline improvements, wanting better access to mental health experts in rural areas, better support networks and visiting specialist coverage, and educational courses tailored to the needs of rural clinicians. Conclusion. Clinicians managing mental health patients in rural and remote Australian EDs lack resources, support services and referral capacity, and access to appropriate education and training. Improvements would better enable access to support and referral services, and educational opportunities. PMID- 22046554 TI - Measuring quality in emergency medical services: a review of clinical performance indicators. AB - Measuring quality in Emergency Medical Services (EMSs) systems is challenging. This paper reviews the current approaches to measuring quality in health care and EMS with a focus on currently used clinical performance indicators in EMS systems (US and international systems). The different types of performance indicators, the advantages and limitations of each type, and the evidence-based prehospital clinical bundles are discussed. This paper aims at introducing emergency physicians and health care providers to quality initiatives in EMS and serves as a reference for tools that EMS medical directors can use to launch new or modify existing quality control programs in their systems. PMID- 22046555 TI - Molecular Network Associated with MITF in Skin Melanoma Development and Progression. AB - Various environmental and genetic factors affect the development and progression of skin cancers including melanoma. Melanoma development is initially triggered by environmental factors including ultraviolet (UV) light, and then genetic/epigenetic alterations occur in skin melanocytes. These first triggers alter the conditions of numerous genes and proteins, and they induce and/or reduce gene expression and activate and/or repress protein stability and activity, resulting in melanoma progression. Microphthalmia-associated transcription factor (MITF) is a master regulator gene of melanocyte development and differentiation and is also associated with melanoma development and progression. To find better approaches to molecular-based therapies for patients, understanding MITF function in skin melanoma development and progression is important. Here, we review the molecular networks associated with MITF in skin melanoma development and progression. PMID- 22046556 TI - Bone marrow stem cell derived paracrine factors for regenerative medicine: current perspectives and therapeutic potential. AB - During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC) therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM) can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy. PMID- 22046557 TI - Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/gamma chain Mice. AB - Humanized bone-marrow xenograft models that can monitor the long-term impact of gene-therapy strategies will help facilitate evaluation of clinical utility. The ability of the murine bone-marrow microenvironment in NOD/SCID versus NOD/SCID/gamma chain(null) mice to support long-term engraftment of MGMT(P140K) transduced human-hematopoietic cells following alkylator-mediated in vivo selection was investigated. Mice were transplanted with MGMT(P140K)-transduced CD34(+) cells and transduced cells selected in vivo. At 4 months after transplantation, levels of human-cell engraftment, and MGMT(P140K)-transduced cells in the bone marrow of NOD/SCID versus NSG mice varied slightly in vehicle- and drug-treated mice. In secondary transplants, although equal numbers of MGMT(P140K)-transduced human cells were transplanted, engraftment was significantly higher in NOD/SCID/gamma chain(null) mice compared to NOD/SCID mice at 2 months after transplantation. These data indicate that reconstitution of NOD/SCID/gamma chain(null) mice with human-hematopoietic cells represents a more promising model in which to test for genotoxicity and efficacy of strategies that focus on manipulation of long-term repopulating cells of human origin. PMID- 22046558 TI - Immune recovery after cyclophosphamide treatment in multiple myeloma: implication for maintenance immunotherapy. AB - Multiple myeloma (MM) is a progressive B-lineage neoplasia characterized by clonal proliferation of malignant plasma cells. Increased numbers of regulatory T cells (Tregs) were determined in mouse models and in patients with MM, which correlated with disease burden. Thus, it became rational to target Tregs for treating MM. The effects of common chemotherapeutic drugs on Tregs are reviewed with a focus on cyclophosphamide (CYC). Studies indicated that selective depletion of Tregs may be accomplished following the administration of a low-dose CYC. We report that continuous nonfrequent administrations of CYC at low doses block the renewal of Tregs in MM-affected mice and enable the restoration of an efficient immune response against the tumor cells, thereby leading to prolonged survival and prevention of disease recurrence. Hence, distinctive time-schedule injections of low-dose CYC are beneficial for breaking immune tolerance against MM tumor cells. PMID- 22046559 TI - Haploidentical hematopoietic stem-cell transplantation in adults. AB - Haploidentical hematopoietic stem-cell transplantation is an alternative transplant strategy for patients without an HLA-matched donor. Still, only half of patients who might benefit from transplantation are able to find an HLA matched related or unrelated donor. Haploidentical donor is readily available for many patients in need of immediate stem-cell transplantation. Historical experience with haploidentical stem-cell transplantation has been characterised by a high rejection rate, graft-versus-host disease, and transplant-related mortality. Important advances have been made in this field during the last 20 years. Many drawbacks of haploidentical transplants such as graft failure and significant GVHD have been overcome due to the development of new extensive T cell depletion methods with mega dose stem-cell administration. However, prolonged immune deficiency and an increased relapse rate remain unresolved problems of T cell depletion. New approaches such as partial ex vivo or in vivo alloreactive T cell depletion and posttransplant cell therapy will allow to improve immune reconstitution in haploidentical transplants. Results of unmanipulated stem-cell transplantation with using ATG and combined immunosuppression in mismatched/haploidentical transplant setting are promising. This paper focuses on recent advances in haploidentical hematopoietic stem-cell transplantation for hematologic malignancies. PMID- 22046560 TI - Paracrine molecules of mesenchymal stem cells for hematopoietic stem cell niche. AB - Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are both adult stem cells residing in the bone marrow. MSCs interact with HSCs, they stimulate and enhance the proliferation of HSCs by secreting regulatory molecules and cytokines, providing a specialized microenvironment for controlling the process of hematopoiesis. In this paper we discuss how MSCs contribute to HSC niche, maintain the stemness and proliferation of HSCs, and support HSC transplantation. PMID- 22046561 TI - Breast cancer stem cells survive periods of farnesyl-transferase inhibitor induced dormancy by undergoing autophagy. AB - A cancer stem cell has been defined as a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. These tumor-forming cells could hypothetically originate from stem, progenitor, or differentiated cells. Previously, we have shown that breast cancer cells with low metastatic potential can be induced into a reversible state of dormancy by farnesyl transferase inhibitors (FTIs). Dormancy was induced by changes in RhoA and RhoC GTPases. Specifically, RhoA was found to be hypoactivated while RhoC was hyperactivated. In the current study we demonstrate that these dormant cells also express certain known stem cell markers such as aldehyde dehydrogenase I (ALDHI) and cluster of differentiation 44 (CD44). We also show that autophagy markers Atg5, Atg12, and LC3-B are expressed in these dormant stem cell-like breast cancer cells. Inhibiting autophagy by inhibitor 3-methyladenine (3-MA) blocked the process of autophagy reversing the dormant phenotype. Further, we show that c-jun NH2 terminal kinase (JNK/SAPK) is upregulated in these dormant stem cell-like breast cancer cells and is responsible for increasing autophagy. PMID- 22046562 TI - One-Year Safety Analysis of the COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133 Bone Marrow Stem Cells to Placebo in Patients after Acute Myocardial Infarction and Left Ventricular Dysfunction. AB - Bone marrow stem cell therapy has emerged as a promising approach to improve healing of the infarcted myocardium. Despite initial excitement, recent clinical trials using non-homogenous stem cells preparations showed variable and mixed results. Selected CD133(+) hematopoietic stem cells are candidate cells with high potential. Herein, we report the one-year safety analysis on the initial 20 patients enrolled in the COMPARE-AMI trial, the first double-blind randomized controlled trial comparing the safety, efficacy, and functional effect of intracoronary injection of selected CD133(+) cells to placebo following acute myocardial infarction with persistent left ventricular dysfunction. At one year, there is no protocol-related complication to report such as death, myocardial infarction, stroke, or sustained ventricular arrhythmia. In addition, the left ventricular ejection fraction significantly improved at four months as compared to baseline and remained significantly higher at one year. These data indicate that in the setting of the COMPARE-AMI trial, the intracoronary injection of selected CD133(+) stem cells is secure and feasible in patients with left ventricle dysfunction following acute myocardial infarction. PMID- 22046563 TI - Recent advances in the pathogenesis and management of cast nephropathy (myeloma kidney). AB - Multiple myeloma is an incurable plasma cell malignancy that is often accompanied by renal failure; there are a number of potential causes of this, of which cast nephropathy is the most important. Renal failure is highly significant in myeloma, as patient survival can be stratified by the severity of the renal impairment. Consequently, there is an ongoing focus on the pathological basis of cast nephropathy and the optimal treatment regimens in this setting, including effective chemotherapy regimens to reduce light chain production and emerging extracorporeal techniques to remove circulating light chains. This paper bridges recent advances in the pathogenesis and management of cast nephropathy in multiple myeloma. PMID- 22046564 TI - Signaling proteins and transcription factors in normal and malignant early B cell development. AB - B cell development starts in bone marrow with the commitment of hematopoietic progenitors to the B cell lineage. In murine models, the IL-7 and preBCR receptors, and the signaling pathways and transcription factors that they regulate, control commitment and maintenance along the B cell pathway. E2A, EBF1, PAX5, and Ikaros are among the most important transcription factors controlling early development and thereby conditioning mice homeostatic B cell lymphopoiesis. Importantly, their gain or loss of function often results in malignant development in humans, supporting conserved roles for these transcription factors. B cell acute lymphoblastic leukemia is the most common cause of pediatric cancer, and it is characterized by unpaired early B cell development resulting from genetic lesions in these critical signaling pathways and transcription factors. Fine mapping of these genetic abnormalities is allowing more specific treatments, more accurately predicting risk profiles for this disease, and improving survival rates. PMID- 22046565 TI - Factors influencing the abundance of the side population in a human myeloma cell line. AB - Side population (SP) refers to a group of cells, which is capable to efflux Hoechst 33342, a DNA-binding dye. SP cells exist both in normal and tumor tissues. Although SP abundance has been used as an indicator for disease prognostic and drug screening in many research projects, few studies have systematically examined the factors influencing SP analysis. In this study we aim to develop a more thorough understanding of the multiple factors involved in SP analysis including Hoechst 33342 staining and cell culture. RPMI-8226, a high SP percentage (SP%) human myeloma cell line was employed here. The results showed that SP% was subject to staining conditions including: viable cell proportion, dye concentration, staining cell density, incubation duration, staining volume, and mix interval. In addition, SP% was highest in day one after passage, while dropped steadily over time. This study shows that both staining conditions and culture duration can significantly affect SP%. In this case, any conclusions based on SP% should be interpreted cautiously. The relation between culture duration and SP% suggests that the incidence of SP cells may be related to cell proliferation and cell cycle phase. Maintaining these technical variables consistently is essential in SP research. PMID- 22046566 TI - Future perspectives: therapeutic targeting of notch signalling may become a strategy in patients receiving stem cell transplantation for hematologic malignancies. AB - The human Notch system consists of 5 ligands and 4 membrane receptors with promiscuous ligand binding, and Notch-initiated signalling interacts with a wide range of other intracellular pathways. The receptor signalling seems important for regulation of normal and malignant hematopoiesis, development of the cellular immune system, and regulation of immune responses. Several Notch-targeting agents are now being developed, including natural receptor ligands, agonistic and antagonistic antibodies, and inhibitors of intracellular Notch-initiated signalling. Some of these agents are in clinical trials, and several therapeutic strategies seem possible in stem cell recipients: (i) agonists may be used for stem cell expansion and possibly to enhance posttransplant lymphoid reconstitution; (ii) receptor-specific agonists or antagonists can be used for immunomodulation; (iii) Notch targeting may have direct anticancer effects. Although the effects of therapeutic targeting are difficult to predict due to promiscuous ligand binding, targeting of this system may represent an opportunity to achieve combined effects with earlier posttransplant reconstitution, immunomodulation, or direct anticancer effects. PMID- 22046567 TI - Hyperbaric oxygen therapy as a sole agent is not immunosuppressant in a highly immunogenic mouse model. AB - Background. Hyperbaric oxygen (HBO) therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD). If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B) mice received skin graft from CBA (H2D) white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model. PMID- 22046568 TI - Multiple myeloma: a review of imaging features and radiological techniques. AB - The recently updated Durie/Salmon PLUS staging system published in 2006 highlights the many advances that have been made in the imaging of multiple myeloma, a common malignancy of plasma cells. In this article, we shall focus primarily on the more sensitive and specific whole-body imaging techniques, including whole-body computed tomography, whole-body magnetic resonance imaging, and positron emission computed tomography. We shall also discuss new and emerging imaging techniques and future developments in the radiological assessment of multiple myeloma. PMID- 22046570 TI - A Case of Monoclonal Lymphoplasmacytosis of the Bone Marrow with IgM-Positive Russell Bodies. AB - A 71-year-old Japanese male patient infected with HCV was diagnosed with thrombocytopenia. Histological examination of the bone marrow aspirate showed numerous lymphoid aggregates with Russell bodies. Immunohistochemistry and flow cytometric analysis demonstrated clonal expansion of CD5+ CD23+ B cells. Russell bodies were positive for IgM and lambda immunoglobulin light chain. The patient also underwent gastric biopsy, which revealed Helicobacter pylori (HP) infection. Subsequent eradication of the bacteria resulted in improvement of his thrombocytopenia. The clinical course remained uneventful at 15-month follow-up, consistent with monoclonal B-cell lymphocytosis. The observed clonal expansion with plasmacytic differentiation may have occurred under the influence of HCV with HP infection. PMID- 22046569 TI - Oncolytic virotherapy for multiple myeloma: past, present, and future. AB - Multiple myeloma (MM) is a B-cell malignancy that is currently felt to be incurable. Despite recently approved novel targeted treatments such as lenalidomide and bortezomib, most MM patients' relapse is emphasizing the need for effective and well-tolerated therapies for this deadly disease. The use of oncolytic viruses has garnered significant interest as cancer therapeutics in recent years, and are currently under intense clinical investigation. Both naturally occurring and engineered DNA and RNA viruses have been investigated preclinically as treatment modalities for several solid and hematological malignancies. Presently, only a genetically modified measles virus is in human clinical trials for MM. The information obtained from this and other future clinical trials will guide clinical application of oncolytic viruses as anticancer agents for MM. This paper provides a timely overview of the history of oncolytic viruses for the treatment of MM and future strategies for the optimization of viral therapy for this disease. PMID- 22046571 TI - Transplantation for congenital bone marrow failure syndromes. AB - Congenital bone marrow failure syndromes (BMFSs) are relatively rare disorders characterized by aberrant development in one or more hematopoietic lineages. Genetic alterations have now been identified in most of these disorders although the exact role of the molecular defects has yet to be elucidated. Most of these diseases are successfully managed with supportive care, however, treatment refractoriness and disease progression-often involving malignant transformation may necessitate curative treatment with hematopoietic stem cell transplantation. Due to the underlying molecular defects, the outcome of transplantation for BMFS may be dramatically different than those associated with transplantation for more common diseases, including leukemia. Given recent improvements in survival and molecular diagnosis of bone marrow failure syndrome patients presenting at adult ages without physical stigmata, it is important for both pediatric and adult hematologists to be aware of the possible diagnosis of BMF syndromes and the unique approaches required in treating such patients. PMID- 22046572 TI - Antibody-based therapies in multiple myeloma. AB - The unmet need for improved multiple myeloma (MM) therapy has stimulated clinical development of monoclonal antibodies (mAbs) targeting either MM cells or cells of the bone marrow (BM) microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic recombination for humanizing rodent mAbs has allowed large-scale production and designation of mAbs with better affinities, efficient selection, decreasing immunogenicity, and improved effector functions. These advancements of antibody engineering technologies have largely overcome the critical obstacle of antibody immunogenicity and enabled the development and subsequent Food and Drug Administration (FDA) approval of therapeutic Abs for cancer and other diseases. PMID- 22046573 TI - Innovative analyses support a role for DNA damage and an aberrant cell cycle in myelodysplastic syndrome pathogenesis. AB - We used flow cytometry to analyze the cell cycle, DNA damage, and apoptosis in hematopoietic subsets in MDS marrow. Subsets were assigned using CD45, side scatter, CD34, and CD71. Cell cycle fractions were analyzed using DRAQ 5 (DNA content) and MPM-2 (mitoses). DNA damage was assessed using p-H2A.X, and apoptosis using Annexin V. Compared to controls, MDS patients demonstrated no increased mitoses in erythroid, myeloid, or CD34+ cells. Myeloid progenitors demonstrated increased G2 cells, which with no increased mitoses suggested delayed passage through G2. Myeloid progenitors demonstrated increased p-H2A.X, consistent with DNA damage causing this delay. Annexin V reactivity was equivalent in MDS and controls. Results for each parameter varied among hematopoietic compartments, demonstrating the need to analyze compartments separately. Our results suggest that peripheral cytopenias in MDS are due to delayed cell cycle passage of marrow progenitors and that this delayed passage and leukemic progression derive from excessive DNA damage. PMID- 22046574 TI - T-cell costimulatory molecules in acute-graft-versus host disease: therapeutic implications. AB - Acute Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation. Although this process is thought to consist of several phases, T-cell activation plays a critical role in the pathogenesis of acute GVHD. To become efficient effectors, T-cells require additional costimulation after T-cell receptor signaling. A number of molecules are involved in costimulation of T-cells such as CD28, CD40L, CD30, OX40, 4-1BB, ICOS, and LIGHT. The system is regulated by inhibitory molecules, CTLA-4, and PD 1. There is experimental evidence that those molecules are implicated in the pathogenesis of GHVD. We describe how these molecules are involved in acute GVHD and how the blockade of costimulatory molecules may have potential implications for the treatment of patients with acute GVHD. PMID- 22046575 TI - Operative outcomes for cervical myelopathy and radiculopathy. AB - Cervical spondylotic myelopathy and radiculopathy are common disorders which can lead to significant clinical morbidity. Conservative management, such as physical therapy, cervical immobilisation, or anti-inflammatory medications, is the preferred and often only required intervention. Surgical intervention is reserved for those patients who have intractable pain or progressive neurological symptoms. The goals of surgical treatment are decompression of the spinal cord and nerve roots and deformity prevention by maintaining or supplementing spinal stability and alleviating pain. Numerous surgical techniques exist to alleviate symptoms, which are achieved through anterior, posterior, or circumferential approaches. Under most circumstances, one approach will produce optimal results. It is important that the surgical plan is tailored to address each individual's unique clinical circumstance. The objective of this paper is to analyse the major surgical treatment options for cervical myelopathy and radiculopathy focusing on outcomes and complications. PMID- 22046576 TI - Rap2A Is Upregulated in Invasive Cells Dissected from Follicular Thyroid Cancer. AB - The development of molecular biomarkers (BMs) of follicular thyroid carcinoma is aimed at advancing diagnosis of follicular neoplasm, as histological examination of those tumors does not lend itself to definitive diagnosis of carcinoma. We assessed the relative levels of expression of 6 genes: CCND2, PCSK2, PLAB, RAP2A, TSHR, and IGF-1R in archived thyroid tissue. The quantitative real-time PCR analysis revealed a significant change in 3 genes: PSCK2 (a 22.4-fold decrease, P = 2.81E - 2), PLAB (an 8.3-fold increase, P = 9.81E - 12), and RAP2A (a 6.3-fold increase, P = 9.13E - 10) in carcinoma compared with adenoma. Expression of PCSK2 was equally low, PLAB was equally high, whereas RAP2A expression was significantly higher (25.9-fold, P = 0.039) in microdissected carcinoma cells that have invaded through the thyroid capsule and entered blood vessels than in thyroid tumor cells growing under the capsule. Thus, RAP2A appeared as a unique and worthy of further evaluation candidate BM associated with invasion of thyroid follicular cells. PMID- 22046577 TI - A preliminary report on disordered speech with deep brain stimulation in individuals with Parkinson's disease. AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proven effective in treating the major motor symptoms of advanced Parkinson's disease (PD). The aim of this study was to learn which laryngeal and articulatory acoustic features changed in patients who were reported to have worse speech with stimulation. Six volunteers with PD who had bilateral STN electrodes were recorded with DBS turned on or off. Perceptual ratings reflected poorer speech performance with DBS on. Acoustic measures of articulation (corner vowel formants, diphthong slopes, and a spirantization index) and phonation (perturbation, long-term average spectrum) as well as verbal fluency scores showed mixed results with DBS. Some speakers improved while others became worse on individual measures. The magnitude of DBS effects was not predictable based on the patients' demographic characteristics. Future research involving adjustments to stimulator settings or electrode placement may be beneficial in limiting the negative effects of DBS on speech. PMID- 22046578 TI - The PIT: SToPP Trial-A Feasibility Randomised Controlled Trial of Home-Based Physiotherapy for People with Parkinson's Disease Using Video-Based Measures to Preserve Assessor Blinding. AB - Purpose. To trial four-week's physiotherapy targeting chair transfers for people with Parkinson's disease (PwPD) and explore the feasibility of reliance on remote outcome measurement to preserve blinding. Scope. We recruited 47 PwPD and randomised 24 to a focused home physiotherapy programme (exercise, movement strategies, and cueing) and 23 to a control group. We evaluated transfers (plus mobility, balance, posture, and quality of life) before and after treatment and at followup (weeks 0, 4, 8, and 12) from video produced by, and questionnaires distributed by, treating physiotherapists. Participants fed back via end-of-study questionnaires. Thirty-five participants (74%) completed the trial. Excluding dropouts, 20% of questionnaire data and 9% of video data were missing or unusable; we had to evaluate balance in situ. We noted trends to improvement in transfers, mobility, and balance in the physiotherapy group not noted in the control group. Participant feedback was largely positive and assessor blinding was maintained in every case. Conclusions. Intense, focused physiotherapy at home appears acceptable and likely to bring positive change in those who can participate. Remote outcome measurement was successful; questionnaire followup and further training in video production would reduce missing data. We advocate a fully powered trial, designed to minimise dropouts and preserve assessor blinding, to evaluate this intervention. PMID- 22046579 TI - Capsaicin-sensitive afferentation represents an indifferent defensive pathway from eradication in patients with H. pylori gastritis. AB - AIM: To study the role of capsaicin-sensitive afferent nerves in Helicobacter pylori (H. pylori) positive chronic gastritis before and after eradication. METHODS: Gastric biopsy samples were obtained from corpus and antrum mucosa of 20 healthy human subjects and 18 patients with H. pylori positive chronic gastritis (n = 18) before and after eradication. Traditional gastric mucosal histology (and Warthin-Starry silver impregnation) and special histochemical examinations were carried out. Immunohistochemistry for capsaicin receptor (TRVP1), calcitonin gene related peptide (CGRP) and substance P (SP) were carried out by the labeled polymer immunohistological method (Lab Vision Co., USA) using polyclonal rabbit and rat monoclonal antibodies (Abcam Ltd., UK). RESULTS: Eradication treatment was successful in 16 patients (89%). Seven patients (7/18, 39%) remained with moderate complaints, meanwhile 11 patients (11/28, 61%) had no complaints. At histological evaluation, normal gastric mucosa was detected in 4 patients after eradication treatment (4/18, 22%), and moderate chronic gastritis could be seen in 14 (14/18, 78%) patients. Positive immuno-staining for capsaicin receptor was seen in 35% (7/20) of controls, 89% (16/18, P < 0.001) in patients before and 72% (13/18, P < 0.03) after eradication. CGRP was positive in 40% (8/20) of controls, and in 100% (18/18, P < 0.001) of patients before and in 100% (18/18, P < 0.001) after eradication. The immune-staining of gastric mucosa for substance-P was positive in 25% (5/20) of healthy controls, and in 5.5% (3/18, P > 0.05) of patients before and in 0% of patients (0/18, P > 0.05) after H. pylori eradication. CONCLUSION: Distibution of TRVP1 and CGRP is altered during the development of H. pylori positive chronic gastritis. The immune-staining for TRVP1, CGRP and SP rwemained unchanged before and after H. pylori eradication treatment. The capsaicin-sensitive afferentation is an independent from the eradication treatment. The 6 wk time period might not be enough time for the restituion of chronic H. pylori positive chronic gastritis. The H. pylori infection might not represent the main pathological factor in the development of chronic gastritis. PMID- 22046580 TI - Contribution of G71R mutation to Gilbert's syndrome phenotype in a Greek patient: A case report. AB - Gilbert's syndrome is characterized by a benign indirect hyperbilirubinemia. It has often been underestimated and undiagnosed because of its mild symptoms; although it is not as rare as was once believed when its frequency was estimated using data originating from biochemical tests. Based on molecular techniques, the occurrence of Gilbert's syndrome has changed, increasing to 10% in the Caucasian population. This molecular defect was described, by Bosma et al, in 1995, and affects the promoter region of the UGT 1A1 gene. In this case report, our aim is to present a new combination of two molecular defects in a Greek patient with Gilbert's syndrome. A 13-year-old Greek girl was examined for Gilbert's syndrome using molecular techniques, and an uncommon genotype was revealed comprising the rare mutation G71R in trans with A(TA)7TAA motif. The G71R mutation according to the literature, as well as our epidemiological data, is rare in Caucasians, while it is common in Asian populations. This is the first case study in the Greek population to report a new genotype for Gilbert's syndrome manifestation in the Caucasian population. PMID- 22046581 TI - Investigation of the toxic effect of a QDs heterojunction on the interactions between small molecules and plasma proteins by fluorescence and resonance light scattering spectra. AB - The effect of a ZnO#ZnS QDs heterojunction (O#SQDs) on the binding affinities of flavonoid glycosides for bovine serum albumin (BSA) was investigated. The fluorescence intensities of BSA decreased remarkably with increasing concentration of O#SQDs. The magnitudes of the binding constants of flavonoid glycosides for BSA in the presence of O#SQDs were in the range of 10(5)-10(7) L mol(-1), and the number of binding sites per BSA (n) was determined as 1.24 +/- 0.17. O#SQDs increased the affinities of flavonoid glycosides for BSA by about 2.96% to 114.68% depending on their structures. O#SQDs in blood will enhance the transportation of flavonoid glycosidegs in blood and improve their pharmacology effects. From this point, O#SQDs are a perfect candidate for flavonoid glycosides delivery applications. PMID- 22046582 TI - Differentiating intrinsic SERS spectra from a mixture by sampling induced composition gradient and independent component analysis. AB - By generating a composition gradient on a highly uniform SERS substrate and applying independent component analysis, we demonstrate that one can extract the intrinsic SERS spectrum of individual components from SERS spectra obtained from a two-component mixture. PMID- 22046583 TI - Micromechanical measurement of AChBP binding for label-free drug discovery. AB - A potential binding assay based on binding-driven micromechanical motion is described. Acetylcholine binding protein (AChBP) was used to modify a microcantilever. The modified microcantilever was found to bend on application of the naturally occurring agonist (acetylcholine) or the antagonist (nicotine and d tubocurarine). Control experiments show that microcantilevers modified without AChBP do not respond to acetylcholine, nicotine, and d-tubocurarine. K(d) values obtained for acetylcholine, nicotine, and d-tubocurarine are similar to those obtained from radio-ligand binding assays. These results suggest that the microcantilever system has potential for use in label free, drug screening applications. PMID- 22046584 TI - Electrocatalytic reaction of hydrogen peroxide and NADH based on poly(neutral red) and FAD hybrid film. AB - A simple method to immobilize poly(neutral red) (PNR) and flavin adenine dinucleotide (FAD) hybrid film (PNR/FAD) by cyclic voltammetry is proposed. The PNR/FAD hybrid film can be easily prepared on an electrode surface involving electropolymerization of neutral red (NR) monomers and the electrostatic interaction between the positively charged PNR and the negatively charged FAD. It exhibits electroactive, stable, surface-confined, pH-dependent, nano-sized, and compatible properties. It provides good electrocatalytic properties to various species. It shows a sensitivity of 5.4 MUA mM(-1) cm(-2) and 21.5 MUA mM(-1) cm( 2) for hydrogen peroxide (H(2)O(2)) and nicotinamide adenine dinucleotide (NADH) with the linear range of 0.1 MUM-39 mM and 5 * 10(-5) to 2.5 * 10(-4) M, respectively. It shows another linear range of 48.8-355.5 mM with the sensitivity of 12.3 MUA mM(-1) cm(-2) for H(2)O(2). In particular, the PNR/FAD hybrid film has potential to replace some hemoproteins to be a cathode of biofuel cells and provide the biosensing system for glucose and ethanol. PMID- 22046585 TI - Direct synthesis of pyrroles via a silver-promoted three-component reaction involving unusual imidazole ring opening. AB - A novel silver-promoted three-component reaction toward the synthesis of multifunctionalized pyrroles has been developed. This reaction involves an unusual imidazole ring decomposition, presumably via 1,5-isomerization and subsequent hydrolysis. PMID- 22046586 TI - A molecular chalice with hydrophobic walls and a hydrophilic rim: self-assembly and complexation properties. AB - We describe the synthesis of a diphenylglycoluril/dibenzo-crown-6 molecular chalice, the self-assembly at the air/water interface and its complexation properties in solution and at the water/chloroform interface. PMID- 22046587 TI - Sorption and separation of CO2 via nanoscale AlO(OH) hollow spheres. AB - The CO(2) uptake on nanoscale AlO(OH) hollow spheres (260 mg g(-1)) as a new material is comparable to that on many metal-organic frameworks although their specific surface area is much lower (530 m(2) g(!1)versus 1500-6000 m(2) g(!1)). Suited temperature-pressure cycles allow for reversible storage and separation of CO(2) while the CO(2) uptake is 4.3-times higher as compared to N(2). PMID- 22046588 TI - Eu(II)-containing cryptates as contrast agents for ultra-high field strength magnetic resonance imaging. AB - The relaxivity (contrast-enhancing ability) of Eu(II)-containing cryptates was found to be better than a clinically approved Gd(III)-based agent at 7 T. These cryptates are among a few examples of paramagnetic substances that show an increase in longitudinal relaxivity, r(1), at ultra-high field strength relative to lower field strengths. PMID- 22046589 TI - A novel bifunctional protein supramolecule for construction of carbon nanotube titanium hybrid material. AB - Carbon nanotube-TiO(2) hybrid materials with many nano-scale cavities were realized using a bifunctional protein supramolecule possessing carbonaceous material-binding peptides and Ti-binding peptides. The obtained structure was confirmed to consist of a central nanotube, surrounding proteins, and a swathing titanium-layer. All processes were carried out at room temperature, using an environmentally friendly method. PMID- 22046590 TI - Antimicrobial surface grafted thermally responsive PNIPAM-co-ALA nano-gels. AB - Thermally responsive Poly(N-isopropylacrylamide) co-allylamine (PNIPAM-co-ALA) nano-gels were synthesised and grafted onto non-woven polypropylene. Silver nitrate was incorporated into the nano-gels in their expanded state and their antimicrobial properties tested. Bacterial growth was measured before and after the Lower Critical Solution Temperature. Below the LCST, bacteria grew, above the LCST bacterial growth was prevented or retarded. PMID- 22046591 TI - On the stereoselective bicyclization of aminodienes catalyzed by chelating diamide complexes of the group 3 metals. A direct comparison of Sc(III) and Y(III) bis(amide)s with an application to the synthesis of alkaloid 195F. AB - Highly diastereoselective bicyclizations of aminodienes catalyzed by chelating diamide complexes of Sc(III) and Y(III) that lead to pyrrolizidines and indolizidines are described. This bis(annulation) procedure has been utilized in a concise synthesis of the pyrrolizidine alkaloid 195F. PMID- 22046592 TI - New animal models of Parkinson's disease. AB - BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder mainly characterized by the loss of dopaminergic neurons from the substantia nigra pars compacta and the presence, in the affected brain regions, of protein inclusions named Lewy Bodies. Despite the fact that numerous mutations causing hereditary forms of Parkinson's disease have been identified in the last decade, current transgenic animal models do not adequately reproduce cardinal features of the human disease. Altogether, the animal models derived of human mutations indicate that the nigrostriatal degenerative process results from the combination of several mechanisms that implicate mitochondrial dysfunction, oxidative damage, and protein degradation impairment. METHODS AND RESULTS: We performed a literature search between 2008 and 2010. DISCUSSION: The absence of adequate in vivo experimental models of Parkinson's disease has severe repercussions for therapeutic intervention success for this incurable neurodegenerative disorder. The present nonexhaustive review looks at invertebrate and mammalian models of Parkinson's disease generated in the last three years. PMID- 22046593 TI - Abstracts of the 81st Annual Meeting of the American Thyroid Association. October 26-30, 2011. Indian Wells, California, USA. PMID- 22046594 TI - Recommended composition of influenza vaccines for use in the 2012 southern hemisphere influenza season. PMID- 22046596 TI - Standardization of terminology of the pandemic A(H1N1) 2009 virus. PMID- 22046595 TI - Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness. PMID- 22046597 TI - Validation of elimination: maternal and neonatal tetanus in Mozambique, 2010. PMID- 22046598 TI - Review of the 2011 winter influenza season, southern hemisphere. PMID- 22046599 TI - [Abstracts XLI Congress of the Spanish Society of Nephrology. October 15-18, 2011. Sevilla, Spain]. PMID- 22046600 TI - Vulvar ulcers and vulvar carcinoma. PMID- 22046601 TI - HIV partner notification is effective and feasible in sub-Saharan Africa: opportunities for HIV treatment and prevention. AB - BACKGROUND: Sexual partners of persons with newly diagnosed HIV infection require HIV counseling, testing and, if necessary, evaluation for therapy. However, many African countries do not have a standardized protocol for partner notification, and the effectiveness of partner notification has not been evaluated in developing countries . METHODS: Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe, Malawi, were randomized to 1 of 3 methods of partner notification: passive referral, contract referral, or provider referral. The passive referral group was responsible for notifying their partners themselves. The contract referral group was given seven days to notify their partners, after which a health care provider contacted partners who had not reported for counseling and testing. In the provider referral group, a health care provider notified partners directly. RESULTS: Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252. Among locatable partners, 107 returned for HIV counseling and testing; 20 of 82 [24%; 95% confidence interval (CI): 15% to 34%] partners returned in the passive referral arm, 45 of 88 (51%; 95% CI: 41% to 62%) in the contract referral arm, and 42 of 82 (51%; 95% CI: 40% to 62%) in the provider referral arm (P < 0.001). Among returning partners (n = 107), 67 (64%) of were HIV infected with 54 (81%) newly diagnosed. DISCUSSION: This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa. Active partner notification was feasible, acceptable, and effective among sexually transmitted infections clinic patients. Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners. PMID- 22046602 TI - A randomized crossover study to determine relative bioequivalence of tenofovir, emtricitabine, and efavirenz (Atripla) fixed-dose combination tablet compared with a compounded oral liquid formulation derived from the tablet. PMID- 22046603 TI - Abstracts of the 22nd Regional Congress of the ISBT (International Society of Blood Transfusion) Asia. Taipei, Taiwan. November 19-23, 2011. PMID- 22046604 TI - Proposal to adjust the WHO clinical staging system. PMID- 22046605 TI - Low uptake of hepatitis C testing and high prevalence of risk behavior among HIV positive injection drug users in Bangkok, Thailand. PMID- 22046610 TI - Abstracts of the 15th Meeting of the Australian and New Zealand Microcirculation Society. November 30-December 3, 2011. Margaret River, Western Australia, Australia. PMID- 22046611 TI - Effects of radial compression on a novel simulated intervertebral disc-like assembly using bone marrow-derived mesenchymal stem cell cell-sheets for annulus fibrosus regeneration. AB - STUDY DESIGN: The aim of this study was to develop a tissue engineering approach in regenerating the annulus fibrosus (AF) as part of an overall strategy to produce a tissue-engineered intervertebral disc (IVD) replacement. OBJECTIVE: To determine whether a rehabilitative simulation regime on bone marrow-derived mesenchymal stem cell cell-sheet is able to aid the regeneration of the AF. SUMMARY OF BACKGROUND DATA: No previous study has used bone marrow-derived mesenchymal stem cell cell-sheets simulated by a rehabilitative regime to regenerate the AF. METHODS: The approach was to use bone marrow-derived stem cells to form cell-sheets and incorporating them onto silk scaffolds to simulate the native lamellae of the AF. The in vitro experimental model used to study the efficacy of such a system was made up of the tissue engineering AF construct wrapped around a silicone disc to form a simulated IVD-like assembly. The assembly was cultured within a custom-designed bioreactor that provided a compressive mechanical stimulation onto the silicone disc. The silicone nucleus pulposus would bulge radially and compress the simulated AF to mimic the physiological conditions. The simulated IVD-like assembly was compressed using a rehabilitative regime that lasted for 4 weeks at 0.25 Hz, for 15 minutes each day. RESULTS: With the rehabilitative regime, the cell-sheets remained viable but showed a decrease in cell numbers and viability. Gene expression analysis showed significant upregulation of IVD-related genes and there was an increased ratio of collagen type II to collagen type I found within the extracellular matrix. CONCLUSION: The results suggested that a rehabilitative regime caused extensive remodeling to take place within the simulated IVD-like assembly, producing extracellular matrix similar to that found in the inner AF. PMID- 22046612 TI - Factor structure of the Neck Disability Index. PMID- 22046613 TI - Expanded indication for recombinant human bone morphogenetic protein 2. PMID- 22046615 TI - Abstracts of the 43rd Annual Scientific Congress of The Royal Australian and New Zealand College of Ophthalmologists. November 19-22, 2011. Canberra, Australia. PMID- 22046616 TI - Abstracts of Obesity 2011. October 1-5, 2011. Orlando, Florida, USA. PMID- 22046614 TI - Risk factors for medical complication after lumbar spine surgery: a multivariate analysis of 767 patients. AB - STUDY DESIGN: Multivariate analysis of prospectively collected registry data. OBJECTIVE: Using multivariate analysis to determine significant risk factors for medical complication after lumbar spine surgery. SUMMARY OF BACKGROUND DATA: Several studies have examined the occurrence of medical complication after spine surgery. However, many of these studies have been done utilizing large national databases. Although these allow for analysis of thousands of patients, potentially influential covariates are not accounted for in these retrospective studies. Furthermore, the accuracy of these retrospective data collection in these databases has been called into question. METHODS: The Spine End Results Registry (2003-2004) is a collection of prospectively collected data on all patients who underwent spine surgery at our two institutions. Extensive demographic and medical information were prospectively recorded as described previously by Mirza et al. Complications were defined in detail a priori and were prospectively recorded for at least 2 years after surgery. We analyzed risk factors for medical complication after lumbar spine surgery using univariate and multivariate analysis. RESULTS: We analyzed data from 767 patients who met out inclusion criteria. The cumulative incidences of complication after lumbar spine surgery per organ system are as follows: cardiac, 13%; pulmonary, 7%; gastrointestinal, 6.7%; neurological, 8.2%; hematological, 17.5%; and urologic complications, 10.3%. The occurrence of cardiac or respiratory complication after lumbar spine surgery was significantly associated with death within 2 years (relative risk: 6.09 and 10.9, respectively). Several significant risk factors were identified for organ-specific complications. Among these, surgical invasiveness appeared to be the largest risk factor for cardiac, pulmonary, neurological, and hematological complications. CONCLUSION: Risk factors identified in this study can be beneficial to clinicians and patients alike when considering surgical treatment of the lumbar spine. Future analyses and models that predict the occurrence of medical complication after lumbar spine surgery may be of further benefit for surgical decision making. PMID- 22046617 TI - Immunotherapy for advanced prostate cancer: a novel treatment option to improve survival. AB - Prostate cancer is the second leading cause of cancer death in men in the United States. Novel immunotherapies are being investigated to improve survival in patients with advanced disease. Sipuleucel-T (PROVENGE), the first autologous cellular immunotherapy approved by the U. S. Food and Drug Administration, improves survival in men with asymptomatic or minimally symptomatic metastatic castration-resistant (hormone refractory) prostate cancer. PMID- 22046618 TI - 2011 AHCA/NCAL National Quality Awards. Idaho gold. Recipient sees big payoff from listening and learning. PMID- 22046619 TI - Many mountains to climb. AB - Medical groups of all types and sizes stand collectively at a crossroads in the evolution of the healthcare industry in the United States at this point in time. Faced with a welter of issues, from reimbursement concerns to mandates coming out of federal healthcare reofrm and the American Recovery and Reinvestment/Health Information Technology for Economic and Clinical Health (ARRA-HITECH) Act and other legislative and regulatory developments and competing to better serve the needs of both patients and payers and purchasers, the CEOs, CIOs and others leading physician groups are working assiduously to find ways forward that meet the demands of stakeholder groups while also meeting the needs of their practicing physicians. In order to get a sense of where the leaders in the field are at this point in time. Healthcare Informatics Eidtor-in-Chief Mark Hagland gathered together several leaders of pioneering medical groups nationwide through a "virtual roundtable" process late this summer, in which he interviewed successive leaders and "shared forward" their thoughts with the others around this "virtual roundtable". Below are excerpts from the progressive interviews. Capsule profiles of the leaders and their organizations can be found below. Among the many inssues facing these leaders: how to plan for the development of accountable care organizations (ACOs), the patient-centered mdical home model, bundled payments and other federal policy requirements; how to make progress towards meaningful use, under the HITECH Act; how to plan for ongoing infrastructure, interoperability, and mobility development; and how to prioritize a variety of disparate efforts aimed at fulfilling different types of needs. No one medical group leader has all the answers; but our panel of leaders certainly has many important and useful perspectives to share. PMID- 22046620 TI - CMIOs roaring ahead. PMID- 22046621 TI - Living with stigma is still the common experience for mental health service users. PMID- 22046622 TI - [Tickbusters]. PMID- 22046623 TI - [The GP's diagnostic assessment considers all possibilities. Dealing competently with uncertainty]. PMID- 22046624 TI - Effects of combination of fluticasone propionate and salmeterol xinafoate on lung function improvement in patients with bronchiectasis. AB - INTRODUCTION: Bronchiectasis is defined as bronchial abnormal and permanent dilation with destructive and inflammatory changes of bronchial wall. Bronchodilators are used to treat the disease in order to improve lung functions. Seretide is the combination of fluticasone propionate and salmeterol xinafoate (FLU/SAL). The effect of each has been proved in the improvement of bronchiectasis, while their synthetic effect as FLU/SAL on bronchiectasis improvement has not been studied yet. AIM: The aim of this study was to investigate the effects of FLU/SAL on the lung function improvement in bronchiectasis patients, comparing and interpreting pulmonary function tests before and after FLU/SAL inhalation. METHODS AND MATERIALS: Twelve patients with bronchiectasis who referred to Rasoul-e-Akram Hospital, Tehran, Iran in 2008 participated in this prospective quasi-experimental trial. The patients were treated with 2 puffs of fluticasone 125 MUg and salmeterol 50 MUg (Seretide) twice a day for one month. Beside recording demographic variables, the results of pulmonary function tests (PFT) including vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and FEV1/FVC ratio were recorded before and after the treatment. Data were analyzed using SPSS v.16 and Pearson correlation and paired T-test were performed. RESULTS: Among 12 patients with bronchiectasis, there were 4 men and 8 women with the mean age of 47.58 (SD=18.32) yr. The mean increase in the ratios of VC, FVC and FEV1 to predicted values and also patients FEV1/FVC after treatment were 15.50% (SD=14.40), 49.83% (SD=8.19) 8.17% (SD=12.07) and 7.17% (SD=12.68), respectively. The results of paired T-test indicated that VC (P=0.008) and FEV1(P=0.039) have increased significantly after treatment. CONCLUSION: This study is one of the first studies investigating the FLU/SAL effect on bronchiectasis. Results of this study have indicated that using FLU/SAL has a significant effect on the improvement of lung function parameters in these patients, while the attention was been focused on antibiotic therapy or other bronchodilators. PMID- 22046625 TI - Melanoma sentinel lymph node biopsy: analysis of cases operated on from 1999 to 2008 in The University Hospital Dubrava, Zagreb, Croatia. AB - TITLE: Melanoma Sentinel Lymph Node Biopsy: analysis of cases operated on from 1999-2008 in the University Hospital Dubrava, Zagreb, Croatia. AIM: To determine how well tumor thickness, ulceration, location and patient age and sex predict a positive sentinel lymph node in the analyzed population. PATIENTS AND METHODS: 321 patients were included in the study. 53% (169) were male and 47% (152) were females. 291 underwent sentinel lymph node biopsy. The median age was 56 years (age range 20-89). Sentinel lymph node biopsy was performed by lymphoscintigraphy using technetium-99m (99mTc)-labeled sulfur colloid and vital dye. RESULTS: Melanomas were similarly distributed on the trunk (154, 48%) and the extremities (145, 45%), a small number was located on the head and neck (12, 4%) and for 10 (3%) there was no record of the location. Positive lymph nodes were detected in 76 (26%) out of 291 patients who underwent sentinel lymph node biopsy. Micrometastases were found in 50 basins (60%), macrometastases were found in 15 basin (18%), one basin contained a metastasis that was spreading beyond the capsule (1%) and in the remaining 18 (21%) positive basins in the identified sentinel lymph nodes contained only isolated tumor cells. The average melanoma thickness of 3.41mm for sentinel lymph node biopsy positive melanomas was significantly greater than 2.47mm for negative melanomas (p=0.006). Proportionally more positive sentinel lymph nodes were found with increasing tumor thickness, (p=0.061). Ulceration was found to be a good predictor of positive sentinel lymph nodes (p<0.001). When comparing upper and lower extremities, sentinel lymph nodes were significantly more positive when the primary melanoma was on the legs (p=0.04). An ulcerated primary melanoma on the extremities was found more likely to have a positive sentinel lymph node (p=0.04). A significantly higher proportion of those older than 50 years old had positive lymph nodes (p<0.001). CONCLUSION: Tumor thickness, ulceration, location (upper vs. lower extremities, on the extremities with ulceration) as well as the age of the patient (>50) were found to be predictors of sentinel lymph node positivity. Clinically negative patients with any of these factors should be considered candidates for sentinel lymph node positivity. PMID- 22046626 TI - Evaluation of the simvastatin effects in the treatment of pulmonary hypertension (PH). AB - BACKGROUND: Pulmonary hypertension (PH) is a rare but life-threatening disease characterized by significant increases in pulmonary arterial pressure (PAP) and right ventricular hypertrophy (RVH), therefore early diagnosis and proper treatment of PH is very important. Statins confer cardiovascular benefits beyond the reduction of serum cholesterol through antiproliferative and antiinflammatory mechanisms and induction of endothelial nitric oxide expression. In pneumonectomized rats injected with monocrotaline, simvastatin reversed established pulmonary hypertension and conferred a 100% survival advantage. OBJECTIVE: The aim of this study was to evaluate the potential effect of simvastatin treatment in patients with pulmonary hypertension (PH). PATIENTS AND METHODS: In this prospective before-after pilot trial, 19 patients with primary and secondary causes of PH referred to Khorrami Hospital in Qom, Iran were recruited. Patients were treated with simvastatin, beginning at 20 mg/daily for 2 months, then increasing to 40 mg/daily for another 4 months. Echocardiographic Doppler estimates of systolic pulmonary artery pressures (SPAP) were measured for each patient before prescribing simvastatin and at the end of treatment. Also demographic data, history of smoking and heart functional class (NYHA) before and after treatment were recorded. RESULTS: Out of 19 patients with PH, fifteen were males (78.95%) and four were females (21.1%) with the mean age of 66 (SD=15.28) yr, range between 18 to 83 years. The commonest cause of PH was chronic obstructive pulmonary disease (COPD) in 15 patients (78.9%). Simvastatin significantly ameliorated PH from 74.79 (SD=23.52) mmHg to 67.21 (SD=20.55) mmHg (P<0.001). Whereas, heart functional class changes were not statistically significant (P=0.157). CONCLUSION: In this study, we demonstrated that simvastatin treatment decreased SPAP in patients with PH. As the pathogenesis of PH involves inappropriate proliferation and constriction of vascular smooth muscle cells, and deficiencies of endogenous vasodilators such as prostacyclin and endothelial-derived nitric oxide, the antiproliferative, antiinflammatory and antithrombogenic effect of simvastatin seems to be useful. This study has led physicians to believe that simvastatin may be beneficial for the treatment of PH. PMID- 22046627 TI - Treatment of symptomatic coronary artery disease with stent implantation. AB - BACKGROUND: Percutaneous coronary intervention (PCI) with stent implantation is the therapy of choice for treatment of decreased blood flow through the coronary arteries. AIM: We evaluated the efficacy of the bare metal stent (BMS) for treatment of symptomatic coronary artery disease and compared BMS with the drug eluting stent (DES) to find out which one is better in the prevention of major adverse cardiac events (MACE) six months after stent implantation. MATERIALS AND METHODS: Our retrospective analysis included 387 consecutive patients with BMS implantation and 74 consecutive patients with DES implantation. Efficacy of BMS was evaluated by residual in-stent stenosis after the procedure. According to the Taxus II-Trial definition, MACE include cardiac death, acute myocardial infarction (AMI) and target vessel revascularization; the latter includes PCI with stent implantation or coronary artery bypass graft on previously revascularized vessel. RESULTS: In BMS group mean pre-procedure stenosis diameter was 81.9 +/- 12.8% and mean post-procedure stenosis was 4.8% +/- 12.5%. The residual in-stent stenosis was significantly higher in patients with longer lesions (p<0.05). Hypertension was the most frequent risk factor in both groups and AMI the commonest indication for stent implantation in the group with BMS, while stable and unstable angina pectoris in the group with DES, respectively. During the first six months after the implantation of DES, the incidence of MACE was significantly lower (p<0.05) compared to BMS. The most frequent subgroup of MACE present in the group with BMS was cardiac death, and in the group with DES it was repeated PCI with stent implantation. CONCLUSIONS: BMS provides and efficacious choice of treatment for patients with symptomatic coronary artery disease. Patients with longer lesions have higher residual in-stent stenosis after BMS implantation. Implantation of DES is more successful in preventing MACE in comparison with the implantation of BMS. PMID- 22046628 TI - Bibliometric analysis of primary care research, childhood obesity, the importance of understanding small area data and diabetes. PMID- 22046629 TI - Retraction. Detection of ubiquityl-calmodulin conjugates with a novel high molecular weight ubiquitylprotein-isopeptidase in rabbit tissues. PMID- 22046630 TI - The discovery of histone deacetylase. PMID- 22046631 TI - Historical development of pediatric pharmacology. PMID- 22046632 TI - Medicare program; final waivers in connection with the Shared Savings Program. Interim final rule with comment period. AB - This interim final rule with comment period establishes waivers of the application of the Physician Self-Referral Law, the Federal anti-kickback statute, and certain civil monetary penalties (CMP) law provisions to specified arrangements involving accountable care organizations (ACOs) under section 1899 of the Social Security Act (the Act) (the Shared Savings Program), including ACOs participating in the Advance Payment Initiative. Section 1899(f) of the Act, as added by the Affordable Care Act, authorizes the Secretary to waive certain fraud and abuse laws as necessary to carry out the provisions of section 1899 of the Act. PMID- 22046633 TI - Medicare program; Medicare Shared Savings Program: Accountable Care Organizations. Final rule. AB - This final rule implements section 3022 of the Affordable Care Act which contains provisions relating to Medicare payments to providers of services and suppliers participating in Accountable Care Organizations (ACOs) under the Medicare Shared Savings Program. Under these provisions, providers of services and suppliers can continue to receive traditional Medicare fee-for-service (FFS) payments under Parts A and B, and be eligible for additional payments if they meet specified quality and savings requirements. PMID- 22046634 TI - Spinal cord injuries. PMID- 22046635 TI - Arterial vascularization of the spinal cord. Recent studies of the anastomotic substitution pathways. AB - This study of the arterial blood of the spinal cord indicates that, of the 62 radicular branches (rami radiculares), at the most seven or eight truly participate in the vascularization of the spinal cord. The authors have observed that the situation and distribution of these branches enable the distinction of three large arterial areas: cervicothoracic, midthoracic, and thoracolumbar. The fixed nature of the intramedullary arterial distribution contrasts with the variability of the afferent arterial supplies. No demarcation permits separation of the vascularization of the spinal cord into anterior and posterior parts. The anastomotic systems situated on the arterial pathways are potentially valuable, but their functioning is problematical. The anterior spinal artery is not continuous, for in the midthoracic region there exists a critical narrow zone. The perimedullary anastomotic system appears insufficient while intramedullary anastomoses are without functional value. PMID- 22046636 TI - The microvasculature in transitory traumatic paraplegia. An electron microscopic study in the monkey. AB - Fine structural alterations in the microvasculature, primarily of the gray matter, occur as one aspect of experimental spinal cord contusion. A force of 300 gm-cm, shown by the authors to produce a transitory paraplegia, was applied to the T-10 level of exposed primate spinal cord. At 5 min post-contusion, the muscular venules of the central gray matter were distended with erythrocytes. Erythrocytes were seen within the perivascular spaces of the post-capillary venules and muscular venules at 15 and 30 min post-contusion, and there was hemorrhage into the gray matter at 1 hour post-contusion. The appearance of erythrocytes within the perivenular spaces was apparently due to small ruptures in the walls of the muscular venules, which were first demonstrated by electron microscopy 15 min after contusion. Alterations in capillary and post-capillary venule endothelium of both gray and white matter were present at 4 hours post contusion and consisted of vacuolation and endothelial swelling. In conclusion, following experimental contusion of the spinal cord sufficient to cause a transitory paraplegia, the principal changes were early perivascular and parenchymal hemorrhages followed by later evidence of ischemic endothelial injury in the microvasculature. PMID- 22046637 TI - Histopathology of transitory traumatic paraplegia in the monkey. AB - The microscopic appearance of the primate spinal cord within a 4-hour interval following the delivery of a direct force sufficient to produce a transitory paraplegia was investigated by light microscopy. The resulting hemorrhagic lesion involved primarily the central gray matter and was attributed to the direct effect of the trauma on the vessels in the gray matter with a consequent impairment of blood supply to the injured area. Chromatolysis, vacuolation, and alterations in cytoplasmic density and stainability were observed within the neurons. The edematous changes in the white matter, which were more marked in the internal layers relative to the external layers, appeared minimal and explain in part why the paraplegia was transient. PMID- 22046638 TI - Microangiographic study of experimental spinal cord injuries. AB - The pathology of spinal cord injury has been studied in 34 rabbits and 5 dogs with attention focused on the condition of the microvasculature during the evolution of neuronal and axonal degeneration and necrosis. The animals were killed and perfused arterially with colloidal barium from 10 min to 14 days after a controlled spinal injury. Microradiographs of the injured tissues were obtained and compared with corresponding histological sections. Microangiography at 7 to 14 days defines two zones in the injured spinal cord. Zone 1 is located in the posterocentral part of the cord. Capillaries in this region progressively lose their ability to conduct blood and perfusate over the first 4 hours. Degenerative changes in neurons are visible by 1 hour after injury. Necrosis of all elements including capillaries ensues. Zone 2 surrounds Zone 1. Microvascular patterns are normal in Zone 2 although neuronal and axonal degeneration is severe. Pericapillary hemorrhages which occur as early as 10 min after injury in Zone 1 and become progressively larger over the first 4 hours seldom are seen in Zone 2. The evidence indicates that at all times in the pathogenesis of spinal cord injury the microvasculature in Zone 2 is capable of perfusion. Degeneration of neural structures either precedes microvascular breakdown (Zone 1) or occurs in the absence of microvascular disruption (Zone 2). Recovery of damaged neurons and axons depends upon a preserved microcirculation. PMID- 22046639 TI - Denervation hyperpathia: a convulsive syndrome of the spinal cord responsive to carbamazepine therapy. AB - Two cases of denervation hyperpathia that responded well to treatment with carbamazepine are presented. A theoretical relation of this disorder to trigeminal neuralgia and focal seizures is emphasized in the light of experimental data and clinical characteristics. PMID- 22046640 TI - Surgical treatment of multiple aneurysms and of incidentally-discovered unruptured aneurysms. AB - Review of a series of 460 patients with spontaneous intracranial hemorrhage showed that 241 had demonstrable aneurysms and 38 had multiple aneurysms. The importance of demonstrating the entire circulation following ligation of one aneurysm is emphasized. Treatment of the 38 patients with multiple aneurysms is described. Ligation of unruptured aneurysms that are incidentally discovered is advocated in patients who are Grade 1 on the Botterell scale and who are well informed as to the risks. PMID- 22046641 TI - Angiographic demonstration of brain injury without significant mass lesion. AB - Evidence of brain damage was demonstrated in two patients without significant mass lesions by the presence of early venous filling and abnormal contrast staining. The vascular changes were most prominent on subtraction films. It is likely that these angiograms demonstrated the "luxury perfusion" phenomenon described previously in areas of damaged brain. PMID- 22046642 TI - The deposition of Hg203-chlormerodrin in experimental brain tumors. AB - The deposition of Hg203-chlormerodrin was studied in intracranial tumors in mice induced by implantation of 20-methyl cholanthrene by tissue assay, as well as light microscopic and electron microscopic autoradiography. The investigations were carried out in astrocytomas, glioblastomas, and meningeal tumors. The chlormerodrin content of the tumors exceeded that of normal brain with a significant tumor/brain ratio ranging from 5.8 to 22.5. It was found that the chlormerodrin molecule becomes rapidly incorporated in the tumor cells, with a preference for that portion of the cytoplasm associated with the vacuolar system. PMID- 22046643 TI - Ventriculoatrial shunt in tuberculous meningitis with hydrocephalus. AB - Raised intracranial tension affects the course of tuberculous meningitis adversely. The development of hydrocephalus may account for the raised intracranial pressure. Insertion of a ventriculoatrial shunt significantly alters the course of the disease. The results in seven cases have been detailed and discussed. The levels of consciousness improved, hemiplegia and aphasia practically cleared up, and vision returned even in children who were blind for 4 to 6 weeks. Operation could be performed even in an active stage of the disease without much fear of miliary dissemination. PMID- 22046644 TI - Pre- and postoperative electromyographic evaluations in the carpal tunnel syndrome. AB - Twenty-five cases of carpal tunnel syndrome in 20 patients were evaluated preoperatively and postoperatively by electromyography. Clinical improvement resulted in all cases following decompression of the median nerve, and only in a few instances did mild symptoms persist. Distal motor conduction time im proved postoperatively in 24 cases studied, 19 of which returned to normal range. Most of the obvious improvement occurred within the first 3 months and further improvement could be observed as late as 36 months. Although no definite correlation could be established between the preoperative severity of the carpal tunnel syndrome and the postoperative clinical and electrical im provement, there was a definite evidence of better recovery in the younger age group. There was a greater range of improvement and a return closer to normal postoperatively in cases with severe preoperative distal latency. All cases ex amined after 24 months had reached normal values. PMID- 22046645 TI - Simple cysts of the cerebellum. AB - Four cases of simple cyst of the cerebellum treated at Stanford University Medical Center are presented. Review of the literature and past experience at Stanford suggest that they are uncommon. They seem to occur most often in middle age, presenting the signs and symptoms of an expanding cerebellar mass, and appear to be adequately treated by unroofing and draining the cyst cavity. It is suggested that these cysts do not have a congenital origin but rather represent a degenerated form of cerebellar astrocytoma. PMID- 22046648 TI - Lipoma of the spinal cord. Case report. AB - A case of intradural spinal lipoma has been reported. Its pathological and clinical features are compared with those of 129 other cases collected from the literature. PMID- 22046646 TI - Transfemoral vertebral angiography as a cause of an anterior spinal artery syndrome. Case report. AB - A case with signs of a lower cervical anterior spinal artery syndrome incident to vertebral angiography by the transfemoral approach is described. The literature is reviewed and a probable pathogenesis of angiography-related spinal cord injury is discussed. PMID- 22046647 TI - Osteoid osteoma of the cervical spine. Case report. AB - A case of osteoid osteoma involving the cervical vertebral pedicle is presented which reemphasizes the importance of complete removal of the nidus and the dramatic relief of symptoms following excision. PMID- 22046649 TI - Dysphagia secondary to anterior cervical osteophytes. Report of two cases. AB - Two cases of dysphagia secondary to anterior cervical osteophytes were successfully treated at the University of Oregon Medical School by surgical excision of the osteophytes. In both cases the cervical osteophytes caused mechanical obstruction to deglutition by esophageal compression. Postoperative x ray examination confirmed relief of obstruction. Related cases, clinical features, diagnostic steps, and possible mechanisms are discussed. PMID- 22046650 TI - Survival following gunshot wound of the pons: neuroanatomic considerations. Case report. AB - The successful treatment of a civilian gunshot wound of the vermis and pons is described. A large missile fragment was removed from a depth of 2 cm within the pons at the level of the facial colliculus. Despite initial coma and subsequent irregular respiration with sleep apnea, the patient survived. Neurological, radiographic, and operative findings are correlated with the anatomy of the pons. PMID- 22046651 TI - Retrograde migration of the venous catheter as a complication of ventriculoatrial shunts in adults. Case report. AB - The retrograde cephalad migration of the flexible venous catheter into a large internal jugular vein is described in two cases of adult "normal" pressure hydrocephalus treated with Holter ventriculoatrial shunts. The successful correction of this problem by replacement of the standard type "C" catheter with a slightly more rigid catheter and internal jugular vein ligation is described. PMID- 22046652 TI - An internal shunt for use in the reconstruction of dural venous sinuses. Technical note. AB - A technique is described for construction and use of an internal shunt which provides hemostasis and permits blood flow through the injured sinus during the period of repair. An illustrative case is presented. PMID- 22046653 TI - A soluble internal splint for experimental vascular anastomosis. Technical note. AB - The authors have developed, in dogs, a nonsuture vascular anastomosis utilizing plastic adhesive and a water-soluble spindle tube composed of 80% saccharose, 16% glucose, and 4% dextrin. The patency rate of end-to-end arterial anastomosis was 70% in arteries with an external diameter of 2.5 to 4.0 mm. The device is easily applied, saves time, and does not require any special instruments. PMID- 22046654 TI - Percutaneous cordotomy. AB - The essentials for performing a safe and satisfactory percutaneous cordotomy are: (1) a suitable type of pain in a patient without respiratory hazard, (2) a very fine electrode, (3) contrast visualization of the dentate ligament, (4) electrical stimulation before lesion making, (5) slow increase in strength of the lesion-making current, (6) careful motor as well as sensory testing between lesions, (7) a willingness to desist in the face of difficulties, and (8) an awareness of the possibility of respiratory problems in the postoperative period. PMID- 22046655 TI - The International Symposium on Head Injuries. PMID- 22046656 TI - [Extended medical education--at any cost?]. PMID- 22046657 TI - [EU questions Swedish internship which is now under investigation]. PMID- 22046658 TI - [Gender and myocardial infarction. Treatment measures not the same as results]. PMID- 22046659 TI - [Alcohol during early pregnancy damages human stem cells. Important that pregnant women receive information about new knowledge from an experimental study]. PMID- 22046660 TI - [Preoperative withdrawal of drugs that affect hemostasis. Evidence-based recommendation]. PMID- 22046661 TI - [Neonatal and maternal risks with IVF are small and decreasing]. PMID- 22046662 TI - [Difficult to treat lithium-associated hyperparathyroidism with surgery. Evidence for optimal therapy is still missing]. PMID- 22046663 TI - [A pediatric lack of knowledge. FPIES--a non-IGF-mediated food allergy with dramatic symptoms]. PMID- 22046664 TI - [Clinical nutrition should be reintroduced as medical specialty!]. PMID- 22046665 TI - [Mobile phones and brain tumours--a scientific controversy]. PMID- 22046667 TI - Few nurses make NHS top jobs list. PMID- 22046666 TI - [Beyond the physician's knowledge map. Important to see the patient as a human being--not the other way round]. PMID- 22046668 TI - "Don't experiment with skill mix without rigorous assessment". PMID- 22046669 TI - "We don't need time travel to know that PFI was unwise". PMID- 22046670 TI - Attitudes towards Gypsy Travellers. AB - Gypsy Travellers often experience wide-ranging inequalities, associated with poor access to health services and education, discrimination, and health professionals' lack of understanding of the cultural identity and health needs of their community. This article explores nurses' attitudes to Gypsy Travellers, and discusses how overcoming bias and negativity can help address the health needs of this community. PMID- 22046671 TI - Defibrillation 2: Using defibrillators in hospital. AB - Patients who have a cardiac arrest in hospital should, if it is indicated, be defibrillated as quickly as possible--ideally within three minutes. Most hospital wards and other clinical areas have access to defibrillators with both advisory (semi-automated) and manual modes. The former enables first responders, including nurses without ECG interpretation skills, to defibrillate the patient while awaiting the arrival of the cardiac arrest team who can then select and use the manual mode. Most hospital nurses will be trained in advisory defibrillation, while a few will be trained in manual defibrillation. This article provides an overview of defibrillation in hospital, and looks at both advisory and manual defibrillation. PMID- 22046672 TI - Implementing nurse-led discharge. AB - Many hospitals have for years tried to introduce nurse-led discharge but the evidence suggests this has not been entirely successful. Projects have failed due to lack of engagement from staff, failure to monitor outcomes and lack of sustainability. This article describes the early stages of the introduction of nurse/midwife-led discharge at the Heart of England Foundation Trust, which attempted to address these issues. PMID- 22046673 TI - Improving the hydration of hospital patients. AB - Dehydration occurs when the body loses fluids at a greater rate than it takes in. For some patients, achieving a fluid balance is difficult without assistance and they rely on interventions by health professionals. In 2009, a fluid balance audit was carried out in an acute hospital. The aim was to identify whether clinical practice could be improved, and if health professionals could assist their patients' hydration during their admission by using a hands-free drinks system. PMID- 22046674 TI - Local winner. PMID- 22046675 TI - Values are vital to overall success. PMID- 22046676 TI - [Can we avoid going in the wrong direction?]. PMID- 22046677 TI - [Facial palsy: update for the practitioner]. AB - The clinical significance of facial palsy hinges on its psychosocial consequences. While its causes are very numerous, several infections account for a majority of cases: Lyme disease, geniculate zoster (Ramsay Hunt syndrome), while the role of HSV-1 in essential (Bell's) palsy remains controversial. Essentials of facial palsy management are discussed, including the importance of the functional grading of palsy, the complexity of Lyme disease serological diagnosis, and its treatment using doxycycline, antiviral and steroids treatment of geniculate zoster, while regarding essential facial palsy, only steroids, but not antiviral have been shown to improve functional recovery. PMID- 22046678 TI - [Advantage of facial rehabilitation after facial palsy]. AB - Visible and immediate trauma, facial palsy (FP) covers functional but also psychological damage and it is essential to evaluate before a comprehensive therapeutic care tailored. Few patients, however, are emerging with a prescription for rehabilitation after a consultation. Why? This rehabilitation is it ignored? Is it absolutely necessary? It is evident in the extension of medical care to minimize the effects. Yet the foundation of rehabilitation is sadly little known and often poorly enforced. In addition to its specificity, this therapy preceded by a report called "pretreatments offers a prognosis for recovery to patient" regardless of the origin and degree of involvement of the PF. PMID- 22046679 TI - [Surgical facial reanimation after persisting facial paralysis]. AB - Facial reanimation following persistent facial paralysis can be managed with surgical procedures of varying complexity. The choice of the technique is mainly determined by the cause of facial paralysis, the age and desires of the patient. The techniques most commonly used are the nerve grafts (VII-VII, XII-VII, cross facial graft), dynamic muscle transfers (temporal myoplasty, free muscle transfert) and static suspensions. An intensive rehabilitation through specific exercises after all procedures is essential to archieve good results. PMID- 22046680 TI - [HPV associated head and neck cancers]. AB - The incidence of oropharyngeal squamous cell carcinoma is rising and this increase is linked to sexual behaviors. Viral and epidemiological studies have linked tonsillar and base of tongue carcinoma with a human papilloma virus (HPV) infection. The patients involved are usually younger and do not exhibit other risk factors such as smoking and alcohol abuse. HPV positive squamous cell carcinoma are associated with a better prognosis than other head and neck carcinoma. Differences in the carcinogenesis mechanisms open options for different and specific oncologic treatments and the potential for prevention of these HPV-related carcinoma by vaccination. PMID- 22046681 TI - [Tracheal replacement grafts: current options]. AB - A critical review of publications on tracheal reconstruction is presented. The extent of the resection defect in terms of horizontal circumference or longitudinal extension determines the difficulty of the reconstruction. To allow a valid comparison, a classification of tracheal defects is proposed. The reconstruction materials can be subdivided into synthetic grafts, autografts, allografts, and bioengineering constructs. Reconstruction of tracheal defects greater than half of the tracheal length was not possible until recently. Numerous publications on animal experimental techniques, and rare human case reports show few successful outcomes. During the last five years, new reconstructive options have emerged: autograft of composite flaps mimicking tracheal architecture and bioengineered tracheal constructs. PMID- 22046682 TI - [Carotidynia and Eagle syndrome: two neck pain syndromes to be rediscovered]. AB - Two classical syndromes of upper cervical pain in the carotid region are discussed: carotidynia and Eagle syndrome. In both cases, after an initial period of enthusiasm, poorly defined diagnostic criteria led to frequent wrong diagnosis and poor treatment responses. This led to doubts about the existence of these syndromes. New radiologic diagnostic criteria have emerged and should allow for a more precise diagnosis. With the correct diagnosis, medical and surgical treatments should be better tailored and more efficient. PMID- 22046683 TI - [Wonder and indignation, engine of life, youthfulness of heart]. PMID- 22046684 TI - [Alzheimer disease, an exemplary problem]. PMID- 22046685 TI - [A dizzying end of the week]. PMID- 22046686 TI - [The death penalty: the importance of finding a vein]. PMID- 22046687 TI - [Homosexuality and blood donation (4)]. PMID- 22046688 TI - [Walking around the hospital]. PMID- 22046689 TI - Talon cusps: conservative management. AB - Talons cusp is an uncommon developmental dental anomaly characterized by presence of an accessory cusp like structure projecting from tooth neck towards incisal edge. This anomaly commonly affects permanent dentition than primary dentition. This article describes early diagnosis and management of two patients with talons cusp. Conservative treatment by selective grinding, followed by fluoride varnish application was done. The patients were followed up for one year without any complications. This indicates conservative means of management to be the most desirable way of managing such anomalies. PMID- 22046690 TI - Intra-coronal bleaching in young permanent and primary tooth with biologic perspectives. AB - The odd attracts society in odd manner, as is the case when a patient with discolored tooth smiles. Because of that, pediatric patients have psychological impact. Trauma and pulpal necrosis are the most common causes for discoloration of teeth. If tooth is intact, intra-coronal bleaching is the most conservative and noninvasive treatment modality provided, it is done cautiously. This article intends to present two case-reports of successful intra-coronal bleaching using milder (sodium perborate) and tissue-friendly bleaching agent with walking bleach. PMID- 22046691 TI - Dentistry for Mexicans with special needs: a commentary. AB - There are more than 2 million residents with disabilities in Mexico. Despite national legislation to assure individuals with disabilities needed services, including education and employment, social inclusion of these individuals is difficult since societal views exclude them from functioning as members of a community. While there are no national studies of the dental needs of individuals with disabilities in Mexico, reports of the general population indicate limited use of dental services and the need for increased restorative services. Examples of dental education accreditation standards in other countries are used as models for the improvement in the preparation of dental students to provide services for individual with special needs. PMID- 22046692 TI - Comparison between rotary and manual techniques on duration of instrumentation and obturation times in primary teeth. AB - OBJECTIVE: The aim of this study was to compare the duration of instrumentation and obturation times and quality of root canal filling between rotary and manual instrumentation techniques in primary teeth. STUDY DESIGN: A randomized, controlled clinical trial was performed that included deciduous teeth with pulp necrotic. Forty necrotic teeth were included; 20 were instrumented with a rotary technique (experimental group) and 20 with a manual technique (control group). The time taken for instrumentation and for obturation were recorded in minutes, and the quality of the root canal filling was recorded as optimal, under-filled, or overfilled. RESULTS: The use of the rotary technique diminished the time of instrumentation to 63% and time of obturation to 68%, and it improved the quality of the root canalfilling. CONCLUSION: The use of rotary instruments in the pulpectomy of primary molars represents a promising technique; the time is significantly reduced. PMID- 22046693 TI - Endoflas, zinc oxide eugenol and metapex as root canal filling materials in primary molars--a comparative clinical study. AB - Several materials have been used to fill root canals of primary teeth. Traditionally, zinc oxide eugenol was used for the purpose, until the introduction of calcium hydroxide and iodoform based materials. Another root canal filling material that contains zinc oxide eugenol, calcium hydroxide and iodoform is commercially available as Endoflas. The aim of the study was to evaluate and compare the efficacy of Endoflas, zinc oxide eugenol and Metapex as root canal filling materials. METHOD: A total of forty-five primary molars from children aged 5-9 years were selected for a one stage pulpectomy procedure. Teeth were randomly divided into three groups of fifteen teeth each based on the type of root canal filling material used. All the molars were evaluated clinically and radiographically at regular intervals of 3, 6, 12 and 18 months. The observations were tabulated and statistically analyzed. RESULTS: Endoflas and zinc oxide eugenol showed 93.3% success, whereas a higher percentage of success was observed with Metapex (100%). Overfilling and voids were more commonly seen in teeth filled with Metapex. CONCLUSION: There was no significant difference between the three root canal filling materials. PMID- 22046694 TI - Assessment of pediatricians dental knowledge, attitude and behavior in Jeddah, Saudi Arabia. AB - Early assessment of the oral health status of children has the potential to reduce or even eliminate oral diseases. Parents rarely take their children to dentist early enough to control dental diseases. However, parents contact pediatricians several times even before the child is born and during the child's early life. Accordingly, pediatricians are considered a perfect and reliable source for oral health control and prevention. AIM: To measure the dental knowledge, attitude and behavior (KAB) of pediatricians in the City of Jeddah regarding oral health status and methods for prevention of dental diseases in children. MATERIALS AND METHOD: Questionnaires consisting of 40 demographic and KAB's questions were distributed to all pediatricians in Jeddah city (605 pediatricians). The KABs' questions consisted of general dental knowledge, preventive dental measures, timing for referral, diet counseling, parafunctional habits and handling of traumatized teeth. A score was given for each question. Percentages of total scores of KABs were compared. RESULTS: The response rate of pediatricians in Jeddah city (363) was 60%. Their mean age was 39.57 years. Pediatricians' KABs were found to be unsatisfactory. The most important observation was that the concept of oral health prevention was deficient. Pediatricians' awareness of fissure sealants, fluoride, dietary counseling, time of first dental visits and thumb sucking were quite limited Pediatricians' knowledge was significantly lower than their attitude and behavior's scores. CONCLUSION: In general, pediatricians' knowledge, attitudes and behavior regarding oral health were not satisfactory. PMID- 22046695 TI - Evaluation of primary tooth enamel surface morphology and microhardness after Nd:YAG laser irradiation and APF gel treatment--an in vitro study. AB - OBJECTIVE: Laser irradiation and fluoride has been used as a preventive tool to combat dental caries in permanent teeth, but little has been done for primary teeth which are more prone to caries. The purpose of this study was to evaluate microhardness alterations in the primary tooth enamel after Nd-YAG laser irradiation alone and combined with topical fluoride treatment either before or after Nd-YAG laser irradiation. METHOD: Ten primary molars were sectioned and assigned randomly to: control group, Nd-YAG laser irradiation, Nd-YAG lasing before APF and APF followed by Nd-YAG lasing. The groups were evaluated for microhardness. Surface morphological changes were observed using SEM. RESULTS: Statistical comparisons were performed. The control group's SEM showed a relatively smooth enamel surface and lasing group had fine cracks and porosities. In the lasing + fluoride group a homogenous confluent surface was seen. In the fluoride + lasing group an irregular contour with marked crack propagation was noted. There was a significant increase in the microhardness of the treatment groups. CONCLUSION: Nd-YAG laser irradiation and combined APF treatment of the primary tooth enamel gave morphologically hardened enamel surface which can be a protective barrier against a cariogenic attack. PMID- 22046696 TI - Pulp calcification in traumatized primary teeth: prevalence and associated factors. AB - AIM: To establish the prevalence of pulp calcifications in 946 patients at the Research and Clinical Center of Dental Trauma in Primary Teeth. STUDY DESIGN: The clinical and radiographic records of l675 traumatized primary teeth were evaluated. Statistical analysis was performed using chi-square and univariate logistic regression. RESULTS: 197 (20.8%) patients showed pulp calcification (PC). A total of 250 (14.9%) calcified teeth were observed In most teeth, PC appeared within the first 12 months following trauma. PC prevalence was higher in cases of repeated trauma (29.6%) than in single trauma (16.4%), p < 0.05, with a 2.14 chance of showing pulp calcification when a child suffered recurrent trauma. Most teeth showing calcified pulp, suffered trauma to the supportive tissue (67.4%), being statistically significant in relation to the trauma to dental tissue (p < 0.05). CONCLUSION: PC is a sequelae in cases of trauma to the primary dentition; teeth that suffered recurrent traumatic injuries show higher risk of presenting. PMID- 22046697 TI - Caries protective agents in human milk and bovine milk: an in vitro study. AB - OBJECTIVES: To estimate Calcium and Phosphorus withdrawal from hydroxyapatite in the presence of bovine milk and human milk from which the following protective fractions namely Casein, Whey protein, Lactose and Milk fat have been individually removed and to compare the above protective fractions in human and bovine milk. METHOD: Human milk obtained from lactating mothers in the labor ward of Kshema hospital was subjected to immediate analysis. Bovine milk was obtained from a local dairy. Equal quantities of human milk and bovine milk (1 ml) were separately subjected to the systematic removal of the four milk fractions. As each fraction was removed, the remaining milk samples were subjected to testing. Powdered hydroxyapatite from human dental enamel was subjected to demineralization with the addition of the milk sample under test for 20 minutes. This mixture was then centrifuged. Aliquots of the supernatant were taken for calcium and Phosphorus analysis using photospectrometry. Ten demineralization tests were similarly carried out for every milk fraction for both human and bovine milk separately. Equal samples of whole bovine milk and whole human milk were also subjected to similar testing. RESULTS: The calcium and phosphorus dissolution values were higher when the individual fractions were eliminated from both human milk/enamel samples and bovine milk/enamel samples as compared to the values obtained from whole human milk/whole bovine milk/enamel samples. Further higher calcium and phosphorus dissolution values were observed when the fractions were individually and separately removed from the whole human milk/enamel samples as compared to the corresponding values obtained when these fractions were removed from bovine milk/enamel samples. CONCLUSION: The evaluated milk fraction in bovine milk namely casein, whey protein, lactose and milk fat were individually more caries protective when compared to the corresponding fractions in human milk. PMID- 22046698 TI - Oral rehydration salt-liquid as an alternative storage medium--a preliminary study. AB - OBJECTIVE: To assess the efficacy of Oral Rehydration Salt-Liquid (ORS-L) in the maintenance of the viability of Periodontal ligament cells (PDL). MATERIALS AND METHOD: Twenty freshly extracted teeth were used for this study. They were then randomly divided into 3 groups: Positive control group--5 teeth which were immediately subjected to collagenase assay, without immersing in ORS-L; Negative control group--5 teeth with an extra oral dry time of 24 hours, followed by subjecting to collagense assay without immersing in ORS-L and Test group (ORS-L)- 10 teeth with an extra oral dry period of 30 minutes, followed by immersion in ORS-L for a period of 45 minutes and then subjected to collagenase assay. The mean number of viable PDL cells were counted on a hemocytometer under 20X magnification. RESULTS: The mean number of viable PDL cells was highest in the positive control group. In comparison to the negative control group, the test group showed a higher number of viable PDL cells. CONCLUSION: The study found that ORS-L was an effective solution in maintaining the viability of PDL cells. PMID- 22046699 TI - Ameloblastic fibro-odontoma: a clinicopathologic study of 12 cases. AB - OBJECTIVE: The ameloblastic fibro-odontoma (AFO) is an uncommon odontogenic tumor occurring in childhood with limited reported data on recurrence. The purpose of this AFO study was to review its clinicopathologic features, investigate treatment modalities and establish a recurrence rate. STUDY DESIGN: The clinicopathologic features of 12 new cases of AFO were analyzed and compared with those of 208 cases from the literature, with special emphasis on the clinical behavior, treatment, and recurrence rate. RESULTS: The average age was 9.4 (+/- 6.7) years with a male-to-female ratio of 1.6:1. The mandible was the site of occurrence in 59.5%. The tumor most often presented radiographically as a unilocular mixed density lesion associated with the crown of an impacted tooth. Displacement of teeth, delayed eruption and bony expansion were commonplace. There were 5 recurrences among 68 cases with adequate follow-up for a recurrence rate of 7.4%. All recurrences were attributed to incomplete removal at the time of the initial surgery. CONCLUSIONS: The AFO is a childhood tumor most often affecting the posterior jaws and frequently causing bony expansion with profound affects on the dentition. Conservative surgical removal with extraction of the associated teeth is recommended. The established recurrence rate is less than 10%. PMID- 22046700 TI - Chondroid choristoma: report of a rare case. AB - An 11-year-old girl reported with an intraoral swelling which was noticed by her mother at birth and increased to its present size during the last year A thorough clinical examination did not shed a conclusive diagnosis. This case highlights and discusses the history, clinical features, histologic features, differential diagnosis and the clinical management of this lesion. Awareness of such an entity will enrich the knowledge of the pediatric dentists who may be the first ones to encounter such cases in their day-to-day practice. PMID- 22046701 TI - Oral manifestation associated with multiple pituitary hormone deficiency and ectopic neurohypophysis. AB - Multiple pituitary hormone deficiency (MPHD) is the diminished secretion of all the hormones produced in the anterior lobe of the pituitary gland. The oral manifestation of this condition includes delayed eruption and prolonged retention of primary teeth, delayed formation and eruption of permanent teeth, delay in development and growth of the jaws, tendency towards development of deep bite and enamel disturbances. This paper reports the case of an adolescent patient with MPHD. Clinical examination revealed partial ankylosis and prolonged retention ofprimary second molars, primary maxillary canines and deep bite. Dental treatment included extraction of all molars with prolonged retention preceded by the necessary medical care with clinical and radiographic follow-up afterwards. The patient was also referred to an orthodontist for orthodontic treatment. Patients' medical condition should always be investigated by clinicians when faced with cases of delayed tooth eruption and bone development. PMID- 22046702 TI - A comparative evaluation of intranasal midazolam, ketamine and their combination for sedation of young uncooperative pediatric dental patients: a triple blind randomized crossover trial. AB - OBJECTIVE: The purpose of this study was to evaluate and compare the efficacy and safety of intranasal (IN) administration of midazolam (M), ketamine (K) and their combination (MK) to produce moderate sedation in young, uncooperative pediatric dental patients. STUDY DESIGN: In this three stage crossover trial forty five uncooperative ASA type-1 children, who required dental treatment, were randomly assigned to receive one of the three drugs/combination by IN route during three subsequent visits. The efficacy and safety of the agents were assessed by overall success rate and by monitoring of vital signs, respectively. RESULTS: The onset of sedation was rapid with K as compared to M and MK. The difference was statistically significant (P < 0.01) between K and M. The overall success rate was 89% with K, MK was 84% and 69% with M. The difference between the overall success rates of K and M was statistically significant (P < 0.01). Vital signs were within physiological limits and there were no significant adverse effects with any medication. CONCLUSIONS: M, K and MK are safe and effective by IN route to produce moderate sedation for providing dental care to pediatric dental patients who have been otherwise indicated for treatment under general anesthesia. PMID- 22046703 TI - A digital method to predict the mesiodistal widths of canines and premolars in an Egyptian sample. AB - OBJECTIVE: Treatment planning in the mixed dentition is important for proper tooth alignment. A mixed dentition analysis, should accurately predict the mesiodistal widths of unerupted permanent teeth. The aim of the present study was to determine which sum of mesiodistal widths (MDW) of permanent teeth will be the best predictor for MDW of unerupted permanent canines and premolars. STUDY DESIGN: The study was conducted on 102 Egyptians, 51 males and 51 females, mean age 16.7 +/- 0.5 years with fully erupted permanent teeth, and intact proximal surfaces. Dental casts were obtained and scanned to produce digital images that were used on a specially designed software program to measure the MDW of permanent teeth. Casts were divided into training and validation sets, where 9 models of tooth combinations were used to develop a regression equation that describes the relation between them and sum of MDW of erupted maxillary or mandibular canines, first and second premolars. The validation set was used to test the accuracy of the proposed equation. RESULTS: R2 of regression models ranged from 0.3 (for models #2, 4, 5 and 8) to 0.36for model #1. The highest regression in model #1 (sum of MDW of lower first permanent molars and upper central incisors) indicated a high linear association between the sum of MDW of tooth combination model #1 and the MDWofmaxillary and mandibular permanent canines and premolars. There was no significant difference between the actual and the predicted MDW when the proposed equation was checked for its accuracy in the entire validation set (p > 0.05). CONCLUSION: The combination of the sums of lower permanent first molars and upper permanent central incisors was the best predictor for the MD W of both maxillary and mandibular permanent canines and premolars. The newly proposed prediction equation may be considered clinically useful for mixed dentition analysis in Egyptian subjects. PMID- 22046704 TI - Comparison of some dietary habits on corrosion behavior of stainless steel brackets: an in vitro study. AB - BACKGROUND AND OBJECTIVE: Resistance to corrosion is an advantageous property of orthodontic brackets; however, due to low levels of pH found in the mouth of a patient, localized corrosion may occur This can affect tooth movement by increasing friction between the arch wire and bracket slot and initiate enamel discoloration. Additionally, corrosion causes the release of elements that may lead to cytotoxic and biological side effects. The aim of this study was to compare the amount of corrosion caused by lemon juice, vinegar and Coca-Cola on orthodontic brackets in vitro and then to recommend the most suitable diet during orthodontic treatment. METHOD: Sixty orthodontic brackets in three groups of twenty were immersed in a test solution (Fusamaya-Meyer artificial saliva plus lemon juice, vinegar or Coca-Cola) at a temperature of 37 degrees C +/- 1. Moreover, a negative control consisting of twenty brackets were put in pure artificial saliva. After 6 weeks the amount of corrosion was determined by measuring delta W of mean weights of brackets and the results were analyzed by general linear models (repeated measurement). RESULTS: Significant differences were seen during different weeks of the study (P < 0.001) and different solutions (P < 0.001). This study showed the amount of corrosion in orthodontic brackets was the most for cola followed by vinegar and then lemon juice. In addition, mean differences for cola versus lemon juice was -0.010 (sig. <0.001), vinegar versus lemon juice was -0.006 (sig. = 0.001) and cola versus vinegar was -0.004 (sig. = 0.013). CONCLUSION: Acidic effervescent soft drinks such as cola have to be eliminated or minimized in the nutritional diet of orthodontic patients because of their harmful effects on their brackets. PMID- 22046705 TI - Effect of orthodontic appliances on oral microbiota--6 month follow-up. AB - OBJECTIVE: This study investigates the effect of fixed and removable orthodontic appliances among children on salivary Streptococcus mutans, Lactobacillus sp. and Candida albicans. STUDY DESIGN: The study was conducted on 69 patients aged between 6-17 years who used fixed or removable orthodontic appliances. Five ml samples of unstimulated saliva from each patient were collected at baseline and at the 1, 3 and 6 month periodic controls. Samples were diluted and plated on Mitis Salivarus Agar (MSA), Man Rogosa Sharp Agar (MRS) and Saboroud Dextrose Agar (SDA). The growths on the plates were examined under a stereomicroscope. Numbers of colony forming units (CFU) per plate were counted. For statistical analysis, the paired t test and Chi-Square were used. RESULTS: S mutans and Lactobacillus sp counts increased significantly 6 months after the insertion of fixed/removable orthodontic appliances in the oral cavity. A significant increase for C albicans presence was noted after 3 months compared with baseline for fixed appliances. CONCLUSION: Long-term utilization of orthodontic appliances may have a negative effect on microbial flora and increase the risk of new carious lesions and periodontal problems. Patients should be recalled within short time intervals to be motivated for oral hygiene during their orthodontic therapy. PMID- 22046706 TI - [Epidemiology of viral gastroenteritis in France and Europe]. AB - Continuous surveillance of acute diarrhea in France has been conducted by Inserm's sentinel network of general practitioners (GP) since 1991. Similar GP based studies have been performed in the Netherlands, Austria and the UK. The causes of most cases of acute diarrhea are unclear. In case-controlstudies designed to identify viruses in stools, 35 to 40% of cases and virtually none of the controls were positive for one of 4 major viruses (rotavirus, calicivirus, astrovirus and adenovirus). Thus, no viral cause was identified in more than 60% of patients with acute diarrhea. The causative role of viruses such as torovirus, picobirnavirus, picornavirus and enterovirus 22 has rarely been investigated. Further investigations are needed to identify other viral, bacterial fungal or parasitic causes of acute diarrhea. In France, on average, more than 3 million people (predominantly children) visit a GP for acute diarrhea each year. Most of these patients recover spontaneously within a few days, but the medical, social and economic costs of acute diarrhea are sufficiently high to justify a more aggressive public policy to prevent and control epidemics in Europe. PMID- 22046707 TI - [Gastroenteritis viruses in France and Europe]. AB - Rotaviruses and noroviruses are the main causes of acute gastroenteritis in young children and adults, respectively. Prospective molecular surveillance of rotavirus genotypes in France and Europe shows that circulating strains may vary with the season, locality or country. Rotavirus OK? genotypes G1 and G9 are the most prevalent. Most strains are associated with P[8], showing a certain genotypic stability of rotaviruses currently circulating in Europe and suggesting that vaccination would be effective at least in the short and medium term. However, atypical strains G12 and G8 must be monitored in case they emerge in future. Noroviruses belong to the Caliciviridae family. These single-stranded RNA viruses show major genetic diversity. they are divided into 5 genogroups, which are themselves subdivided into genotypes. In addition, new variants are continually arising, and are frequently associated with new epidemic waves of gastroenteritis. PMID- 22046708 TI - [Viral gastroenteritis in domestic animals and zoonoses]. AB - Etiologic investigations of infectious diarrhea were long limited to bacteria and protozoa. The advent of electron microscopy and molecular biology showed that diarrhea could also be caused by viruses, both in humans and in other animals. In 1969, electron microcopy was used to show, for the first time, the responsibility of a virus in a case of calf diarrhea. This "reo-like virus "was subsequently identified as a rotavirus, and was shown only four years later to be responsible for severe diarrhea in young children. Noroviruses, and particularly the human virus Norwalk, were subsequently discovered, followed by coronavirus, sapovirus, pestivirus, astrovirus, enteric adenoviruses, torovirus, and picobirnavirus. Some of viruses found in animals, and particularly rotaviruses, can also infect humans. Rotaviruses have been identified in numerous animal species and are generally host-specific, but zoonotic transmission has been suggested by cross infection (especially in experimental models), by genetic studies showing a close relationship between certain human and animal rotaviruses, and by the discovery of new animal genotypes during epidemiological surveillance of human rotaviroses. Some animal strains of norovirus, sapovirus, picobirnavirus and astrovirus are genetically related to human strains, but their human transmission has not been demonstrated. PMID- 22046709 TI - [Rotavirus vaccination in Europe in 2010]. AB - The important burden of rotavirus infections in infants largely justifies vaccine prevention. Two attenuated oral vaccines were licensed in Europe in 2006 and have proven effective against severe rotavirus gastroenteritis in infants, yet few countries have implemented vaccination. This hesitation may be related to a very low risk of intussusception in vaccinees, but is mainly due to national differences in cost-effectiveness. PMID- 22046710 TI - [Bone microarchitecture]. AB - Bone mass is determined throughout life by modeling and remodeling mechanisms. Trabecular bone consists of a network of trabeculae (plates and rods) whose distribution is highly anisotropic: trabeculae are disposed parallel to the resultant of stress lines (Wolff's law). The trabecular microarchitecture appears to be conditioned by mechanical stresses exerted on skeletal bones. Few clinically validated methods are available to assess and monitor the bone microarchitecture in bone diseases. The best-developed is bone histomorphometry, with the use of new algorithms to appreciate various 2D characteristics of the trabeculae, such as thickness and connectivity. Several studies have shown that several independent techniques should be used to study microarchitecture parameters. X-ray microtomography (micro CT), microMRI and synchrotron devices can give non destructive 3D measurements of the trabecular microarchitecture of bone specimens. This review describes advances in our knowledge of bone microarchitecture, its role in bone diseases such as osteoporosis, and methods of 2D and 3D histological evaluation. PMID- 22046711 TI - [Management of osteoporosis: room for improvment]. AB - The objective of anti-osteoporotic treatments is the prevention of the first or recurrent fractures. Screening of at risk patients is the basis of improvement of osteoporosis management. Prevalent fractures are strong determinants of incident fractures. In patients without fractures screening of risk factors, and quantification of risk using FRAX tool, allows detection of patients who should receive highest priority for treatment. Several drugs have shown that they are able to decrease the risk of fracture, providing persistence and compliance. Non pharmacological approach (including nutrition and physical activity) is part of optimal management of osteoporosis. PMID- 22046712 TI - [New actors in bone remodelling: a role for the immune system]. AB - Bone metabolism is mainly under estrogenic control. Estrogen induces the expression or activation of transcription factors, leading to phenotypic cellular changes that are critical for the balance between bone formation and resorption. The two activities are linked via the RANK ligand/osteoprotegerin pathway. Fine regulation of bone metabolism and the bone-specific response to estrogen deficiency implies the participation of immune cells, and especially T cells. Indeed, T cells are activated by estrogen deficiency and produce pro-inflammatory cytokines such as TNFalpha, which stimulates osteoclastogenesis both directly and indirectly through the RENKL pathway. Antigen hyperactivity mechanisms may potentiate T cell activation. Other cytokines such as IL-1 and IL-7 also participate in the cross-takl between immune cells and osteoclasts. TGFbeta and IFNgamma modulate these redundant and multiple pathways in a more complex fashion. B cells may also participate, especially after IL-7-induced activation. Although many of these findings remain to be validated in humans, they open up the possibility of new therapeutic approaches, especially given the growing evidence that post-menopausal osteoporosis is associated with a mild chronic inflammatory state. PMID- 22046713 TI - [Advances treatment of osteoporosis: new molecules, new strategies]. AB - Practitioners already have a wide range of effective drugs for the treatment of osteoporosis, but new options are needed to prevent fractures in patients with this chronic and disabling disease. Recent advances in bone cell biology have revealed new specific targets for the treatment of bone loss, based on inhibition of bone resorption by osteoclasts (anti-RANK ligand antibodies and cathepsin K inhibitors) or stimulation of bone formation by osteoblasts (anti-sclerostin antibodies). These future treatments (anti-RANK ligand antibodies should shortly be available) will add osteoporosis to the growing list of disorders amenable to targeted biotherapies. PMID- 22046714 TI - [Spouse violence: treat the bully to save the victim]. AB - Traditionally, the police and judiciary have been rather late in dealing with domestic violence, considering it to be a private matter. However, this form of violence has a tendency to increase in frequency and intensity over time. If the victim's initial complaint is not taken in account, then he or she will become even more isolated, while the offender may see this" official inaction "as justifying his or her deeds. The later the authorities call these perpetrators to book, by reminding them that violence is unacceptable, the more difficult it is to manage and treat them. This is why, in our jurisdiction (Douai, northern France), offenders are transiently excluded from the home. Victims are followed throughout by social workers, who explain the procedure and refer them to a lawyer if they wish to take legal action. They are also introduced to a self support group that includes both victims and psychologists, in order to allow them to share their experience. The public prosecutor encourages the offender to stay in a designated residential center for about ten days, in order to break the cycle of abuse. The aim is to stress that all violence is illegal and to give the offender time to reflect on what led him or her to be violent. After this period of isolation, the offender, whose behavior is assessed on a standardized form, is invited to return home, after being informed that any further violence on their part will lead to an immediate court appearance. Then, during a six-month period, three hours per week, the offender is invited to attend a self-help group that includes psychiatrists and psychologists. The results are satisfactory: between May 2003 and December 2010 the relapse rate stabilized at 6%, a level that seemed impossible to attain in early 2003 when the system was created PMID- 22046715 TI - [Rape: a social problem and a public health issue]. AB - The French legal definition of rape was somewhat vague until the 1970s. In December 1980, the increased awareness created by the feminist movement led to a precise legal definition and to the possibility for self-help groups to participate in legal actions. In 1985, a telephone helpline was created after several rapes were following several rapes committed in public. Since 1986, more than 39 000 women have called this hotline. Other recent studies confirm the frequency of rape. Major advances have been made in recent years, in terms of justice for minors who are victims of rape (lengthening of the statutory limitation on sexual crimes) and healthcare provision (opening of refuges, medical-legal consultations, victim management centers, greater awareness among healthcare professionals, etc.). Women need to be better informed of the frequency of rape, its legal implications, rapists' strategies, mental disorders, and the physical (especially gynecological) repercussions of rape. Women must also be aware that the rapist is the only guilty party. Finally, a multidisciplinary strategy is needed, notably involving self-help associations and hospital units that deal with rape victims. PMID- 22046716 TI - [Contribution of mathematical modeling to vaccination decision making. Examples from varicella, rotavirus and papillomavirus vaccinations]. AB - The decision to add a new vaccine to the immunization schedule is a complex and multidisciplinary process based on the risk-benefit balance and, increasingly, on the cost- effectiveness ratio. Such decisions now use mathematical models that can predict the indirect, and potentially detrimental, effects of mass vaccination on the epidemiology of the target disease. The adjunction of an economic component to the modeling process ensures that vaccination represents an efficient allocation of available financial resources in an increasingly constrained environment. PMID- 22046717 TI - [Diagnostic use of positron emission tomography in France: from the coincidence gamma-camera to mobile hybrid PET/CT devices]. AB - Positron emission tomography (PET) is a well-established medical imaging method. PET is increasingly used for diagnostic purposes, especially in oncology. The most widely used radiopharmaceutical is FDG, a glucose analogue. Other radiopharmaceuticals have recently been registered or are in development. We outline technical improvements of PET machines during more than a decade of clinical use in France. Even though image quality has improved considerably and PET-CT hybrid machines have emerged, spending per examination has remained remarkably constant. Replacement and maintenance costs have remained in the range of 170-190 Euros per examination since 1997, whether early CDET gamma cameras or the latest time-of-flight PET/CT devices are used. This is mainly due to shorter acquisition times and more efficient use of FDG New reimbursement rates for PET/CT are needed in France in order to favor regular acquisition of state-of-the art devices. One major development is the coupling of PET and MR imaging. PMID- 22046719 TI - Mitigation of conflicts with automation: use of cognitive countermeasures. AB - OBJECTIVE: The aim of this study was to empirically assess the efficacy of cognitive countermeasures based on the technique of information removal to enhance human operator attentional disengagement abilities when facing attentional tunneling. BACKGROUND: Lessons learned from human factors studies suggest that conflict with automation leads to the degradation of operators' performance by promoting excessive focusing on a single task to the detriment of the supervision of other critical parameters. METHOD: An experimental setup composed of a real unmanned ground vehicle and aground station was developed to test the efficiency of the cognitive countermeasures.The scenario (with and without countermeasure) involved an authority conflict between the participants and the robot induced by a battery failure.The effects of the conflict and, in particular, the impact of cognitive countermeasures on the participants' cognition and arousal were assessed through heart rate measurement and eye tracking techniques. RESULTS: In the control group (i.e., no countermeasure), 8 out of 12 participants experienced attentional tunneling when facing the conflict, leading them to neglect the visual alarms displayed that would have helped them to understand the evolution of the tactical situation. Participants in the countermeasure group showed lower heart rates and enhanced attentional abilities, and 10 out of 11 participants made appropriate decisions. CONCLUSIONS: The use of cognitive countermeasures appeared to be an efficient means to mitigate excessive focus issues in the unmanned ground vehicle environment. APPLICATIONS: The principle of cognitive countermeasures can be applied to a large domain of applications involving human operators interacting with critical systems. PMID- 22046718 TI - Predictors of computer use in community-dwelling, ethnically diverse older adults. AB - OBJECTIVE: In this study, we analyzed self-reported computer use, demographic variables, psychosocial variables, and health and well-being variables collected from 460 ethnically diverse, community-dwelling elders to investigate the relationship computer use has with demographics, well-being, and other key psychosocial variables in older adults. BACKGROUND: Although younger elders with more education, those who employ active coping strategies, or those who are low in anxiety levels are thought to use computers at higher rates than do others, previous research has produced mixed or inconclusive results regarding ethnic, gender, and psychological factors or has concentrated on computer-specific psychological factors only (e.g., computer anxiety). Few such studies have employed large sample sizes or have focused on ethnically diverse populations of community-dwelling elders. METHOD: With a large number of overlapping predictors, zero-order analysis alone is poorly equipped to identify variables that are independently associated with computer use. Accordingly, both zero-order and stepwise logistic regression analyses were conducted to determine the correlates of two types of computer use: e-mail and general computer use. RESULTS: Results indicate that younger age, greater level of education, non-Hispanic ethnicity, behaviorally active coping style, general physical health, and role-related emotional health each independently predicted computer usage. CONCLUSION: Study findings highlight differences in computer usage, especially in regard to Hispanic ethnicity and specific health and well-being factors. APPLICATION: Potential applications of this research include future intervention studies, individualized computer-based activity programming, or customizable software and user interface design for older adults responsive to a variety of personal characteristics and capabilities. PMID- 22046720 TI - The effect of transverse shear force on the required coefficient of friction for level walking. AB - OBJECTIVE: An enhanced methodology to extract the required coefficient of friction (RCOF) value was used to investigate the effects of the transverse shear component of the ground reaction force (GRF) on the RCOF. BACKGROUND: The RCOF is an important indicator for slip incidents. However,the extraction of the RCOF from GRF is not standardized. The transverse shear force is usually ignored in calculating the RCOF value. METHOD: For this study, 40 participants performed four walking conditions. The RCOF values both with (RCOF2) and without (RCOF1) the transverse shear force were identified from each strike by the use of an enhanced method and were compared. RESULTS: A total of 24,851 strikes were collected. The transverse component increased the RCOF value by more than 10% in 7.2% of the strikes. In 10.4% of the strikes, the RCOF2 occurred at least 20 ms earlier and the RCOF value was on average 8.9% larger than RCOF1. CONCLUSION: With this method, we were able to successfully identify the RCOF in a significantly large number of strikes across 40 participants. In a portion of the strikes, the transverse shear force increased the RCOF significantly. In a significant portion of the strikes, the RCOF2 occurred much earlier than RCOF1. APPLICATION: Better estimates of the RCOF magnitude and instant of occurrence could potentially improve risk assessment and identification of critical instants in gait. PMID- 22046721 TI - Biomechanical effects of mobile computer location in a vehicle cab. AB - OBJECTIVE: The objective of this research is to determine the best location to place a conventional mobile computer supported by a commercially available mount in a light truck cab. BACKGROUND: U.S. and Canadian electric utility companies are in the process of integrating mobile computers into their fleet vehicle cabs. There are no publications on the effect of mobile computer location in a vehicle cab on biomechanical loading, performance, and subjective assessment. METHOD: The authors tested four locations of mobile computers in a light truck cab in a laboratory study to determine how location affected muscle activity of the lower back and shoulders; joint angles of the shoulders, elbows, and wrist; user performance; and subjective assessment. A total of 22 participants were tested in this study. RESULTS: Placing the mobile computer closer to the steering wheel reduced low back and shoulder muscle activity. Joint angles of the shoulders, elbows, and wrists were also closer to neutral angle. Biomechanical modeling revealed substantially less spinal compression and trunk muscle force. In general, there were no practical differences in performance between the locations. Subjective assessment indicated that users preferred the mobile computer to be as close as possible to the steering wheel. CONCLUSION: Locating the mobile computer close to the steering wheel reduces risk of injuries, such as low back pain and shoulder tendonitis. APPLICATION: Results from the study can guide electric utility companies in the installation of mobile computers into vehicle cabs. Results may also be generalized to other industries that use trucklike vehicles, such as construction. PMID- 22046722 TI - Physical fidelity versus cognitive fidelity training in procedural skills acquisition. AB - OBJECTIVE: The current study examined whether training simulators for the acquisition of procedural skills should emphasize physical fidelity or cognitive fidelity of the task. BACKGROUND: Simulation-based training for acquiring and practicing procedural skills is becoming widely established. Generally speaking, these simulators offer technological sophistication but disregard theory-based design, leaving unanswered the question of what task features should be represented in the simulators.The authors compared real-world training and two alternative virtual trainers, one emphasizing physical fidelity and the other cognitive fidelity of the task. METHOD: Participants were randomly assigned to one of four training groups in a LEGO assembly task: virtual-physical fidelity, cognitive fidelity, real world, and control. A posttraining test to assess the development of procedural skills was conducted. RESULTS: Both the virtual physical fidelity and cognitive fidelity training methods produced better performance time than no training at all, as did the real-world training. The cognitive fidelity training was inferior in terms of test time compared to the real-world training, whereas the virtual-physical fidelity training was not. In contrast, only the real-world and the cognitive fidelity groups, and not the virtual-physical fidelity group, required significantly less time than the control group for error correction. CONCLUSION: The two training methods have complementary advantages. APPLICATION: Combining physical fidelity and cognitive training methods can enhance procedural skills acquisition when real-world training is not practicable. PMID- 22046723 TI - Modeling eye gaze patterns in clinician-patient interaction with lag sequential analysis. AB - OBJECTIVE: The aim of this study was to examine whether lag sequential analysis could be used to describe eye gaze orientation between clinicians and patients in the medical encounter. This topic is particularly important as new technologies are implemented into multiuser health care settings in which trust is critical and nonverbal cues are integral to achieving trust. This analysis method could lead to design guidelines for technologies and more effective assessments of interventions. BACKGROUND: Nonverbal communication patterns are important aspects of clinician-patient interactions and may affect patient outcomes. METHOD: The eye gaze behaviors of clinicians and patients in 110 videotaped medical encounters were analyzed using the lag sequential method to identify significant behavior sequences. Lag sequential analysis included both event-based lag and time-based lag. RESULTS: Results from event-based lag analysis showed that the patient's gaze followed that of the clinician, whereas the clinician's gaze did not follow the patient's. Time-based sequential analysis showed that responses from the patient usually occurred within 2 s after the initial behavior of the clinician. CONCLUSION: Our data suggest that the clinician's gaze significantly affects the medical encounter but that the converse is not true. APPLICATION: Findings from this research have implications for the design of clinical work systems and modeling interactions. Similar research methods could be used to identify different behavior patterns in clinical settings (physical layout, technology, etc.) to facilitate and evaluate clinical work system designs. PMID- 22046724 TI - A meta-analysis of factors affecting trust in human-robot interaction. AB - OBJECTIVE: We evaluate and quantify the effects of human, robot, and environmental factors on perceived trust in human-robot interaction (HRI). BACKGROUND: To date, reviews of trust in HRI have been qualitative or descriptive. Our quantitative review provides a fundamental empirical foundation to advance both theory and practice. METHOD: Meta-analytic methods were applied to the available literature on trust and HRI. A total of 29 empirical studies were collected, of which 10 met the selection criteria for correlational analysis and 11 for experimental analysis. These studies provided 69 correlational and 47 experimental effect sizes. RESULTS: The overall correlational effect size for trust was r = +0.26,with an experimental effect size of d = +0.71. The effects of human, robot, and environmental characteristics were examined with an especial evaluation of the robot dimensions of performance and attribute-based factors. The robot performance and attributes were the largest contributors to the development of trust in HRI. Environmental factors played only a moderate role. CONCLUSION: Factors related to the robot itself, specifically, its performance, had the greatest current association with trust, and environmental factors were moderately associated. There was little evidence for effects of human-related factors. APPLICATION: The findings provide quantitative estimates of human, robot, and environmental factors influencing HRI trust. Specifically, the current summary provides effect size estimates that are useful in establishing design and training guidelines with reference to robot-related factors of HRI trust. Furthermore, results indicate that improper trust calibration may be mitigated by the manipulation of robot design. However, many future research needs are identified. PMID- 22046725 TI - Shining new light on the Hawthorne illumination experiments. AB - OBJECTIVE: This study provides an historical and statistical analysis of archival data from the Hawthorne illumination experiments. BACKGROUND: Previous accounts of the illumination experiments are fraught with inconsistencies because they have been based on secondary sources. The general consensus has been that variations in light levels had no effect on worker productivity at Hawthorne. All reports and data were thought to have been destroyed, but an archive at Cornell University was found to contain copies of the original documentation and much of the data from all three illumination experiments. Conclusions were originally drawn from visual comparisons of productivity graphs, and the data have never been properly statistically analyzed. METHOD: Archival reports, notes, photographs, and letters on the experiments were consulted. Productivity data were extracted from the tables and graphs in the reports and statistically analyzed for each experiment. RESULTS: Previously unpublished details of the illumination experiments emerged. An effect of lighting on productivity was found in the first treatment sequence for the first experiment, but this finding was not confirmed in the second sequence or in the second and third experiments. CONCLUSION: Experimental results provided inconsistent evidence of an association between light levels and productivity. All three experiments were found to be seriously flawed. APPLICATION: This study challenges popular accounts of the "Hawthorne effect," and the shortcomings of these experiments also have implications for the design of field studies. PMID- 22046726 TI - Phased training for high-reliability occupations: live-fire exercises for civilian firefighters. AB - OBJECTIVE: The aim of this study was to assess whether the stress reduction effects of phased training culminating in repeated exposure to a stressful scenario generalize to new scenarios. BACKGROUND: High-reliability occupations require personnel to operate in stressful situations involving complex environments, high degrees of uncertainty and time pressure, and severe consequences for mistakes. One method of training for such environments culminates in practice in high-fidelity, highly stressful simulations. For some domains, realism necessitates large-scale, difficult-to-modify physical simulations. This necessity often results in repeated exposure to one or very few scenarios. The literature gives reason to question whether the stress reduction effects of such exposure transfer to new scenarios. METHOD: Anxiety and cognitive difficulties were measured among firefighter trainees during three live-fire drills. For each trainee, two drills involved the same scenario, and the other involved a new scenario that was structurally similar to the repeated scenario. RESULTS: As predicted, anxiety and cognitive difficulties decreased across repetitions of the same scenario. However, the reduction did not generalize to a new scenario, and a nontrivial portion of the sample showed signs of negative transfer. CONCLUSION: Repeated exposure to the same stressful scenario as the final phase of training has limited practical value for stress reduction. Methods for expanding the range of scenarios to which trainees are exposed or for increasing the value of the exposure are recommended. APPLICATION: The findings could help improve design of training programs for high-reliability occupations. PMID- 22046727 TI - Physical and cognitive effects of virtual reality integrated training. AB - OBJECTIVE: The objective of this study was to evaluate the cognitive and physical impact of virtual reality (VR) integrated training versus traditional training methods in the domain of weld training. BACKGROUND: Weld training is very important in various industries and represents a complex skill set appropriate for advanced training intervention. As such, there has been a long search for the most successful and most cost-effective method for training new welders. METHOD: Participants in this study were randomly assigned to one of two separate training courses taught by sanctioned American Welding Society certified welding instructors; the duration of each course was 2 weeks. After completing the training for a specific weld type, participants were given the opportunity to test for the corresponding certification. Participants were evaluated in terms of their cognitive and physical parameters, total training time exposure, and welding certification awards earned. Each of the four weld types taught in this study represented distinct levels of difficulty and required the development of specialized knowledge and skills. RESULTS: This study demonstrated that participants in the VR integrated training group (VR50) performed as well as, and in some cases, significantly outperformed, the traditional welding (TW) training group.The VR50 group was found to have a 41.6% increase in overall certifications earned compared with the TW group. CONCLUSION: VR technology is a valuable tool for the production of skilled welders in a shorter time and often with more highly developed skills than their traditionally trained counterparts. APPLICATION: These findings strongly support the use ofVR integrated training in the welding industry. PMID- 22046728 TI - Twentieth Convocation, Royal Australasian College of Dental Surgeons, Perth, Western Australia, March 2010. Address by the President of the Royal Australasian College of Dental Surgeons Bernadette Drummond, BDS, MS, PhD, FRACDS at the opening ceremony. PMID- 22046729 TI - Twentieth Convocation, Royal Australasian College of Dental Surgeons, Perth, Western Australia, March 2010. Opening address by His Excellency Dr Ken Michael, AC Governor of Western Australia. PMID- 22046730 TI - Twentieth Convocation, Royal Australasian College of Dental Surgeons Perth, Western Australia, March 2010. The Fourteenth Robert Harris Oration. PMID- 22046731 TI - Aesthetics in implant therapy: a blueprint for success and change. AB - High-end implant aesthetics requires precise steps from diagnosis through surgery to the restorative phase. These steps are not exclusive of each other. They are deliberate and require a clear understanding of what is possible and the skills that are required to carry out each procedure. Every small advancement will help in the initial and long-term stability of the treatment. This article will dissect implant treatment into key concepts and procedures, illustrating how these steps are crucial to a highly successful aesthetic outcome. PMID- 22046732 TI - They're only baby teeth; who should care? AB - Despite significant improvements in our understanding of the pathogenesis of dental caries, it remains one of the most common chronic diseases of childhood. Given that few very young children actually attend dental health services, there is a role for non-dental healthcare professionals in the prevention of dental disease and the promotion of oral health. This presentation will take an evidence based approach to explore opportunities for increased collaboration between dental and non-dental healthcare professionals to optimize the health outcomes for children. The role and responsibilities of the dental profession in developing this model of shared care will also be discussed. PMID- 22046733 TI - Molar incisor hypomineralization: clinical management in children. PMID- 22046734 TI - Bisphosphonates and the dental practitioner--a guide to management. AB - The author has been managing osteonecrosis of the jaws (ONJ) for more than six years. This paper will outline the dental management of patients taking bisphosphonates. This will include: 1. The predisposing factors causing ONJ, 2. Its clinical presentation, 3. Staging for the appropriate conservative and surgical management, 4. Guidelines for prevention, 5. Case report. PMID- 22046735 TI - The use of virtual reality tools in surgical education. AB - Advances in computing, specifically those used for simulation and games technology has allowed for exciting developments in dental and surgical education. At the same time concerns are being raised that students with relatively little training, practise to improve their skill on patients with all of the inherent risks that may occur. Simulation in dentistry has been practised for many years and so the concept is not new to the profession. New tools have been developed that both enhance teaching and learning and are also useful for assessment of students and trainees. The challenge of virtual and simulated reality tools is to have the required fidelity to improve teaching and learning outcomes over the currently utilized methodology. PMID- 22046736 TI - Ridge preservation: does it actually work? AB - Post-extraction the alveolus undergoes modelling which reduces height and width. This may present a problem for subsequent crown and bridge or implant therapy. Ridge preservation is the use of grafts and/or membranes to try to minimize the loss of the alveolar ridge. Extraction sockets have been filled with autogenous, allogenic and alloplastic materials. Membranes or soft tissue were used to contain the graft. More recently biodegradable sponges and materials coated in growth factors have been tested. Studies have primarily looked at either maintenance of vertical and horizontal dimensions or the healing of the socket and how much of the graft material is incorporated into the newly formed bone. Irrespective of method or materials, there seems to be some maintenance of the alveolus. Bone fill seems to occur in preserved extraction sockets, but in most cases with a high percentage of residual graft particles. In general, there is a lack of evidence to show that ridge preservation aids in correct 3-D implant placement, maintains hard and soft tissue volume over a prolonged period of time or for success and survival of implants placed into ridge preserved sockets. Still the most effective way to maintain ridge volume is to keep the natural tooth. PMID- 22046737 TI - Novel approaches in 3-dimensional facial profiling to establish facial aesthetic objectives in the treatment of facial dysmorphologies. AB - When confronted with facial dysmorphologies, three-dimensional (3D) facial harmony is preferably assessed with regard to normality. This, however, presents two major challenges. The first challenge is to define normality. What makes non dysmorphic faces appear normal? The second challenge is to situate the craniofacial dysmorphology with respect to normality. What makes the dysmorphic face not appear to be normal? To tackle these challenges, a novel approach based on a Face Space is proposed. In essence, faces are represented as points in a High-dimensional space, the dimensions of which capture important sources of allowed facial variation within a normal population. To establish an aesthetic objective of a given dysmorphic face, the novel concept of the "normal equivalent" of that face via robust projection into the Face Space is proposed. This technique is demonstrated on an artificial example in which smiling whilst showing teeth is considered a surrogate for facial dysmorphology. PMID- 22046738 TI - Aspects of wear and tear of tooth structure. AB - Lifestyle factors and the increased longevity of the dentition due to greater life expectancy have resulted in greater wear and tear (cracking) of teeth. Often there exists interplay between damage and repair. An understanding of these mechanisms of damage and repair will assist the clinician in correct diagnosis and treatment planning. Preventive strategies as well as interdisciplinary measures are required for optimal outcomes. However, are some of our restorative interventions causing further damage to tooth structure? PMID- 22046739 TI - General well-being in the new decade--important considerations. AB - Chronic diseases have created a growing burden of ill-health as populations age, become more obese and as survival with many conditions improves. Cardiovascular disease, cancer and anxiety/depression merit priority by being common and treatable. Genomics aid diagnosis and understanding but have limited impact on management. Early diagnosis requires comprehensive annual clinical reviews, in which dental practitioners have an important role. Relevant imaging can be helpful. Useful early interventions include tactical lifestyle measures, weight control, appropriate supplements and low dose pharmacotherapy. PMID- 22046740 TI - IT and security considerations for online clinical records. AB - E-health and the national electronic medical record are on our doorstep. As an integral part of the healthcare system, dentistry needs to get on board with this national initiative. How prepared is the dental profession for this? How can a culture of online clinical records be promoted and what protocols and infrastructure exist for this to occur? The lack of government restriction means that dentistry should be taking full advantage of what is possible. The benefits and barriers to adoption of online records will be presented to provide a frame of reference for the next major shift in electronic communication. PMID- 22046741 TI - Repair of critical size defects in the rabbit calvarium with the use of a novel scaffold material. AB - A number of materials have been implanted into skull defects to determine if improved healing outcomes can be achieved. In some instances, packing or implanting bone-inducing alloplasts into a standardized skull defect results in better healing than an untreated defect. AlloDerm is a skin derived acellular collagen membrane and has characteristics that are known to be effective in promoting bone growth. It has not been previously investigated for use in cranial bone healing. The aim of the investigation was to determine if implanting this novel scaffold into skull defects will improve the quality of bone repair. Six rabbits received AlloDerm grafts into critical-sized calvarial defects. The rabbits were sacrificed at two months and the specimens examined histologically and radiographically. At the time of sacrifice, it was found that while bony growth had commenced at the margins of the defect and as isolated islands within the graft, there did not appear to be a major benefit in using the material described. PMID- 22046742 TI - Understanding adhesive dentistry. AB - This review paper firstly provides an outline of the development of resin-based adhesives. A simple classification method is described based on whether an acid etching agent requiring a washing and drying step is used. These systems are called etch and rinse systems. The other adhesives that do not have the washing and drying steps are referred to as self-etching adhesives. The advantages and disadvantages of these groups of adhesives are discussed. Methods of adhering to the tooth surface are provided, especially where the resin-based adhesive reliability is difficult to control. PMID- 22046743 TI - The missing link in minimal intervention dentistry: effective caries control. PMID- 22046744 TI - Osseointegration--the influence of implant surface. AB - The modification of implant surfaces from the original machined to 'micro-rough', and more recently 'bioactive', surfaces has been proposed to improve clinical outcomes. This review outlines the evidence for the superior performance of modified implant surfaces. Pre-clinical trials consistently show that modified implant surfaces are more osteogenic and improve the degree of osseointegration. Clinically, there is a clear trend for improved clinical success with 'micro rough' compared with machined implants. This is particularly the case in compromised sites, such as the posterior maxilla, and compromised patients, such as smokers. Furthermore, 'micro-rough' implant surfaces perform better in augmented sites, and facilitate the more predictable use of short implants, thus reducing the need for more invasive augmentation procedures. 'Micro-rough' implants have been associated with an increased susceptibility to peri implantitis, but these findings relate to a surface that is no longer manufactured. Newly developed 'bioactive' surfaces have only been evaluated in a limited number of clinical studies. PMID- 22046745 TI - Understanding risk for periodontal disease. AB - An ability to identify individuals at risk for progressive periodontal disease would enable targeted prevention and treatment, thus reducing the economic burden on society. The importance of the interplay between microbial, genetic and environmental factors in risk assessment is recognized and the relative contributions of various risk factors has been determined. However, newer technologies will enable more accurate individual risk profiling in the future. PMID- 22046746 TI - Coronectomy as the treatment of choice in wisdom teeth showing radiographic signs of close proximity to inferior dental nerve. AB - The aim of the study is to compare the prevalence of post-operative inferior dental nerve (IDN) deficit after coronectomy with total removal of wisdom teeth showing specific radiographic signs of close proximity to IDN. A randomized clinical trial comparing total removal and coronectomy of wisdom tooth was conducted. Analyses of the correlations of IDN deficit and various radiographic signs of wisdom tooth roots showing close proximity to IDN were performed. Two radiographic signs were found to be positive predictors ofintra-operative IDN exposure. Specific radiographic signs or the presence of two or more radiographic signs are positive predictors of post-operative IDN deficit. The study concluded that darkening of the wisdom tooth root and presence of two or more specific signs in radiographs significantly increased the risk of IDN deficit in lower wisdom tooth surgery. Coronectomy can significantly reduce the prevalence of an IDN deficit in patients with lower wisdom teeth showing radiographic signs of close proximity to IDN. It also carries less surgical morbidities when compared with total removal of lower wisdom tooth. PMID- 22046747 TI - Early wound healing following a mechanical cleansing post-surgical protocol--a randomized controlled trial. PMID- 22046748 TI - Making phytoremediation work better: maximizing a plant's growth potential in the midst of adversity. AB - While a number of different plants can either breakdown a variety of organic contaminants or hyperaccumulate metals from the environment, even the most efficient of those plants is typically inhibited by the presence of the toxicant(s). The plant stress that is induced by the presence of various environmental toxicants typically limits a plant's growth and ultimately its ability to phytoremediate the toxicant(s). Here, it is argued that the simple strategy of adding plant growth-promoting bacteria (preferably endophytes) that reduce plant ethylene levels by ACC deaminase activity and have the ability to synthesize the phytohoromone IAA, and are used to phytoremediate various toxicants can significantly (and often dramatically) increase both plant growth and phytoremediation activity in the presence of those toxicants. PMID- 22046749 TI - Use of plasma-based spectroscopy and infrared microspectroscopy techniques to determine the uptake and effects of chromium(III) and chromium(VI) on Parkinsonia aculeata. AB - Chromium uptake and tolerance by Mexican Palo Verde (Parkinsonia aculeata) (MPV) was studied in a six-month experiment with Cr(III) and Cr(VI) at 60 and 10 mg kg( 1), respectively. Chromium and nutrient uptake were determined by ICP-OES and changes in macromolecules were studied by infrared microspectroscopy (IMS). In the Cr(VI)-treated plants, chromium concentration increased in the roots only through the third month, while translocation to stems increased constantly throughout the six months. Cr(III) applications decreased the amount of Zn in leaves and stems (p < or = 0.05). Cr(VI) increased P and S in all plant tissues and increased Ca in roots, but decreased Ca in stems and leaves, and Mg in roots and stems. Cr(III) decreased P in stems and leaves, while both Cr ions decreased K in all MPV tissues. Relative to untreated plant tissue, the IMS revealed significant changes at 1730 cm(-1) and 845 cm(-1). Changes at 1730 cm(-1) indicated that the cortex and xylem of Cr-treated plants were more proteinaceous. Changes at 845 cm(-1) revealed higher lignifications in cortex. However, at the stem level, Cr(VI) decreased lignin deposition in xylem. The data showed that MPV could be useful in the phytoremediation of Cr in moderately impacted soils. PMID- 22046750 TI - Phyto (in)stabilization of elements. AB - The effects of plants (corn, soybean, and sunflower) and fertilizer on mobility of more than 60 elements were assessed in a greenhouse experiment. Unplanted columns with the same soil served as controls. Half the columns received fertilizer and all columns were watered at the same rate. At the end of the experiment, the columns were watered to mimic a rainstorm event such that water drained from the bases of the columns, which was collected and analyzed for element content. Soil from between the roots of the plants was also collected and the water-extractable fraction determined. It was expected that (1) more mobile elements, as measured by water extraction, would be leached from the soils at a higher rate compared to less mobile elements, (2) plants would immobilize most elements, but that some would be immobilized, and (3) that this would depend on plant species. The results led to the following conclusions: plants cause metal mobility to vary over a wide range for a specific soil and do mobilize some elements (e.g., Th) while immobilizing others (e.g., U). The effects depended on plant species for some elements. Water-extractable fractions of elements do not predict mobility. PMID- 22046751 TI - Copper phytoextraction in tandem with oilseed production using commercial cultivars and mutant lines of sunflower. AB - Use of sunflower (Helianthus annuus L.) for Cu phytoextraction and oilseed production on Cu-contaminated topsoils was investigated in afield trial at a former wood preservation site. Six commercial cultivars and two mutant lines were cultivated in plots with and without the addition of compost (5% w/w) and dolomitic limestone (0.2% w/w). Total soil Cu ranged from 163 to 1170 mg kg(-1). In soil solutions, Cu concentration varied between 0.16-0.93 mg L(-1). The amendment increased soil pH, reduced Cu exposure and promoted sunflower growth. Stem length, shoot and capitulum biomasses, seed yield, and shoot and leaf Cu concentrations were measured. At low total soil Cu, shoot Cu mineralomass was higher in commercial cultivars, Le., Salut, Energic, and Countri, whereas competition and shading affected morphological traits of mutants. Based on shoot yield (7 Mg DW ha(-1)) and Cu concentration, the highest removal was 59 g Cu ha( 1). At high total soil Cu, shoot Cu mineralomass peaked for mutants (e.g., 52 g Cu ha(-1) for Mutant 1 line) and cultivars Energic and Countri. Energic seed yield (3.9 Mg air-DW ha(-1)) would be sufficient to produce oil Phenotype traits and shoot Cu removal depended on sunflower types and Cu exposure. PMID- 22046752 TI - Toward protein engineering for phytoremediation: possibilities and challenges. AB - The combination of rational protein engineering and directed evolution techniques allow for the redesign of enzymes with tailored properties for use in environmental remediation. This review summarizes current molecular methods for either altering or improving protein function and highlights examples of how these methods can address bioremediation problems. Although much of the protein engineering applied to environmental clean-up employs microbial systems, there is great potential for and significant challenges to translating these approaches to plant systems for phytoremediation purposes. Protein engineering technologies combined with genomic information and metabolic engineering strategies hold promise for the design of plants and microbes to remediate organic and inorganic pollutants. PMID- 22046753 TI - Exogenous cytokinin treatments of an Ni hyper-accumulator, Alyssum murale, grown in a serpentine soil: implications for phytoextraction. AB - Application of exogenous plant growth regulators was examined as a viable technique to increase the efficiency of plant metal extraction from contaminated soils. The aim of this study was to investigate the alteration of Ni phytoextraction by Alyssum murale, a Ni hyperaccumulator, following the application of cytokinins. The following parameters were investigated: Ni accumulation, plant growth, gas exchange, stomata behavior and the concentration of nonprotein thiols (glutathione, y-Glu-Cys, and phytochelatins). In a pot experiment, A. murale plants grown in a serpentine soil were treated with a mix of naturally occurring cytokinins. Results showed that Ni accumulation in plants ranged from 4000 to 7000 mg kg(-1) confirming the hyper-accumulation ability from the soil used. Cytokinin treatments produced a significant increase in plant biomass and transpiration rate whereas no significant variation in Ni accumulation or the concentration of non-protein thiols was observed. The results suggest that A. murale is a plant species sensitive to cytokinin treatment and that cytokinin treatment is potentially useful in increasing the phytoextraction capability by increasing biomass. Moreover, for first time, evidence was obtained that the Ni hyperaccumulation mechanism is independent of water flux and transpiration rate. PMID- 22046754 TI - Opportunities for woody crop production using treated wastewater in Egypt. I. Afforestation strategies. AB - The Nile River provides nearly 97% of Egypt's freshwater supply. Egypt's share of Nile waters is fixed at 55.5 billion cubic meters annually. As a result, Egypt will not be able to meet increasing water demand using freshwater from the Nile and has been developing non-conventional wastewater reuse strategies to meet future demands. The USAID Mission in Cairo began promoting strategies for water reuse in 2004, and guidelines for safe and direct reuse of treated wastewater for agricultural purposes were approved in 2005 (Egyptian Code 501/2005). Twenty-four man-made forests were established that have been useful for assessing the efficacy of using treated wastewater for afforestation. At present, approximately 4,340 hectares are under irrigation with treated wastewater, utilizing a total daily volume of 467,400 cubic meters. Wastewater has been applied to trees along roads, greenbelts in cities, and woody production systems. Currently, a joint USDA Forest Service--Agricultural Research Service technical assistance team has been evaluating the feasibility of scaling up such afforestation efforts throughout Egypt. We describe information about: 1) suitable tree species that have been identified based on local soil characteristics, water quality, and quantity of water supply; 2) the benefits and consequences of using these species; 3) strategies to maximize the potential of afforestation with regard to improving water quality, maximizing resource production, increasing biodiversity, and limiting commercial inputs; and 4) potential long-term impacts on the natural resource base from afforestation. A companion paper addresses irrigation recommendations based on species and local conditions (see Evett et al. 2000). PMID- 22046755 TI - Opportunities for woody crop production using treated wastewater in Egypt. II. Irrigation strategies. AB - An Egyptian national program targets annual reuse of 2.4 billion m3 of treated wastewater (TWW) to irrigate 84,000 ha of manmade forests in areas close to treatment plants and in the desert. To evaluate the feasibility of such afforestation efforts, we describe information about TWW irrigation strategies based on (1) water use of different tree species, (2) weather conditions in different climate zones of Egypt, (3) soil types and available irrigation systems, and (4) the requirement to avoid deep percolation losses that could lead to groundwater contamination. We conclude that drip irrigation systems are preferred, that they should in most cases use multiple emitters per tree in order to increase wetted area and decrease depth of water penetration, that deep rooting should be encouraged, and that in most situations irrigation system automation is desirable to achieve several small irrigations per day in order to avoid deep percolation losses. We describe directed research necessary to fill knowledge gaps about depth of rooting of different species in sandy Egyptian soils and environments, tree crop coefficients needed for rational irrigation scheduling, and depth of water penetration under different irrigation system designs. A companion paper addresses recommendations for afforestation strategies (see Zalesny et al. 2011, this issue). PMID- 22046756 TI - Quantification of prairie restoration for phytostability at a remediated defense plant. AB - In June 2008 and 2009, cover, density, and species diversity were measured on two areas of the prairie at the U. S. Department of Energy Weldon Spring Site to begin quantification of the prairie establishment and the effects of a prairie burn. Sampling began by testing for the most appropriate transect length (cover) and quadrat size (density) for quantification of vegetation. Total cover increased in the first growing season after burning. Conversely, total cover decreased in the unburned area in one year. The trend in litter cover is the opposite with litter decreasing after burning, but increasing in one year in the unburned area. Bare ground decreased in one year in the unburned area, but was unchanged after burning. Species diversity tripled after fire, but was unchanged in one year in the unburned area. The results show that litter and fire both affect plant cover. If land reclamation activities are to be an integral part of hazardous waste remediation at contaminated sites, then the success of reclamation efforts needs to be quantified along with success criteria for waste remediation of the sites. The results show that plant cover can be easily quantified, but that density measures are more biased which makes it more difficult to achieve adequate sample size for plant density. PMID- 22046757 TI - Effect of calcium on growth performance and essential oil of vetiver grass (Chrysopogon zizanioides) grown on lead contaminated soils. AB - The aim of this study was to investigate effect of calcium on growth, survival, essential oil yield and chemical compositions of vetiver grass grown on lead contaminated soils. Calcium inform of CaCO3 (0, 2000, 4000, 6000 mg Ca kg(-1)) was added to river sand soils containing 4000 mg Pb kg(-1) dry soil. Results showed that, in the absence of calcium treatment, no plants survived after 2 weeks of cultivation, while the rest grew well to the end of the experimental period (42 weeks). Calcium treatments generally resulted in a slight decrease in biomass. Interestingly, an increase in calcium over 2000 mg kg(-1) did not result in a decrease in accumulation of lead in vetiver roots and shoots. The levels of lead in roots and shoots under calcium treatments were around 2000 and 90 mg kg( 1) dry weight, respectively. The addition of CaCO3 did not improve vetiver essential oil yield and chemical composition compared to the control. A level of applied CaCO3 about half of the lead concentration in soils was sufficient to improve vetiver growth and survival, and accumulate high concentrations of lead in the roots. This finding can be applied for re-vegetation of lead contaminated soils using vetiver. PMID- 22046758 TI - Selenium accumulation in plants--phytotechnological applications and ecological implications. AB - Selenium (Se) is an essential trace element for many organisms including humans, yet toxic at higher levels. Both Se deficiency and toxicity are problems worldwide. Since plants readily accumulate and volatilize Se, they may be used both as a source of dietary Se and for removing excess Se from the environment. Plant species differ in their capacity to metabolize and accumulate Se, from non Se accumulators (< 100 mg Se/kg DW), to Se-accumulators (100-1000 mg Se/kg DW) to Se hyperaccumulators (> 1,000 mg Se/kg DW). Here we review plant mechanisms of Se metabolism in these various plant types. We also summarize results from genetic engineering that have led to enhanced plant Se accumulation, volatilization, and/or tolerance, including field studies. Before using Se-accumulating plants at a large scale we need to evaluate the ecological implications. Research so far indicates that plant Se accumulation significantly affects the plant's ecological interactions below and above ground. Selenium canprotect plants from fungal pathogens and from a variety of invertebrate and vertebrate herbivores, due to both deterrence and toxicity. However, specialist (Se-tolerant herbivores), detritivores and endophytes appear to utilize Se hyperaccumulator plants as a resource. These findings are relevant for managing phytoremediation of Se and similar elements. PMID- 22046759 TI - Suspended solids in and turbidity of runoff from green roofs. AB - Green roof technology is used to reduce the quantity of stormwater runoff, but questions remain regarding its impact on quality. This study analyzed the total suspended solids (TSS) in and the turbidity of runoff from green roof growth media mixed with composted pine bark in an indoor pot study. The results showed that there were elevated levels of TSS and turbidity in the runoff that decreased over time for all growth media. Both TSS and turbidity are affected by the type of growth media. Lava and haydite had higher mean TSS and mean turbidity than arkalyte and bottom ash. Vegetation reduced the mean turbidity and mean TSS of the first flush by an average of 53% and 63%, respectively, but generally had no statistically significant effect thereafter. The results indicate that the media, rather than the vegetation, has a greater effect on TSS and turbidity in the runoff In areas with stringent water quality regulations for stormwater runoff from developed sites, media selection may be an important consideration. It may also be necessary in these regions to ensure that the roof is planted prior to receiving rainfall to minimize the first flush effect and that any irrigation does not result in runoff. PMID- 22046760 TI - Short rotation coppice culture of willows and poplars as energy crops on metal contaminated agricultural soils. AB - Phytoremediation, more precisely phytoextraction, has been placed forward as an environmental friendly remediation technique, that can gradually reduce increased soil metal concentrations, in particular the bioavailable fractions. The aim of this study was to investigate the possibilities of growing willows and poplars under short rotation coppice (SRC) on an acid, poor, sandy metal contaminated soil, to combine in this way soil remediation by phytoextraction on one hand, and production of biomass for energy purposes on the other. Above ground biomass productivities were low for poplars to moderate for willows, which was not surprising, taking into account the soil conditions that are not very favorable for growth of these trees. Calculated phytoextraction efficiency was much longer for poplars than these for willows. We calculated that for phytoextraction in this particular case it would take at least 36 years to reach the legal threshold values for cadmium, but in combination with production of feedstock for bioenergy processes, this type of land use can offer an alternative income for local farmers. Based on the data of the first growing cycle, for this particular case, SRC of willows should be recommended. PMID- 22046761 TI - Developing a sustainable phytomanagement strategy for excessive selenium in western United States and India. AB - Phytomanagement technology is recognized as an inexpensive and environmental friendly strategy for managing natural-occurring selenium (Se) in soils and in poor quality waters. Multi-year field and greenhouse studies were conducted with different plant species in California, USA and Punjab, India under high Se growing conditions. Some of the plant species included; canola (Brassica napus), mustard (B. juncea), broccoli (B. oleracea), spearmint (Mentha viridis), sugarcane (Saccharum officcinarum), guar (Cyamopsis tetragonoloba), wheat (Triticum aestivum), and poplar (Populus deltoides). California soils had a sodium-sulfate-dominated salinity between 6-10 dS m(-1), while Indian soils had a calcium carbonate salinity less than 1 dS m(-1). Results demonstrated that high sulfate conditions reduced plant Se accumulation more than 100 x in Californian grown plants compared to Se accumulation in Indian grown plants. Tissue concentrations generally did not exceed 10 and 200 mg kg DM(-1) in leaves of plants grown in California and India, respectively. At these plant concentrations, Se phytomanagement is more effective in Indian soils than in California soils. Successful management of Se by plants requires selecting crops or crop rotations that are tolerant of the soil condition and identifying and creating new viable Se-enriched products. PMID- 22046762 TI - Nickel solubilizing capacity and characterization of rhizobacteria isolated from hyperaccumulating and non-hyperaccumulating subspecies of Alyssum serpyllifolium. AB - Bacterial strains were isolated from the rhizosphere of three populations of the Ni-hyperaccumulator Alyssum serpyllifolium subsp. lusitanicum (A. pintodasilvae; M, S, and L), one population of Ni-hyperaccumulator A. serpyllifolium subsp. malacitanum (A. malacitanum; SB), and one population of the non-hyperaccumulator A. serpyllifolium subsp. serpyllifolium (A. serpyllifolium; SN). Isolates were characterized genotypically by BOX-PCR genomic DNA fingerprinting and comparative sequence analysis of partial 16S rRNA gene, and phenotypically by their Ni tolerance (0-10 mM), presence of plant growth promoting traits (indoleacetic acid (IAA)-, siderophore-, or organic acid-production, and phosphate solubilization) or capacity to produce biosurfactants. Among the collection of rhizobacteria, 84 strains were selected (according to their BOX-PCR profiles and phenotypic characteristics) to assess their ability to modify Ni extractability from Ni-rich (serpentine) soils. Metabolites produced by 13 of the isolates mobilized soil Ni (originating from the rhizosphere of both Ni-hyperaccumulators and non hyperaccumulator). In contrast, Ni extraction using culture medium filtrates which had supported the growth of 29 strains was significantly reduced. The remaining strains had no effect on Ni mobility. Bacterial induced Ni mobilization was not related to Ni resistance or the phenotypic traits tested. Isolates with potential use in phytoremediation techniques will be further studied in a plant microorganism-soil system. PMID- 22046763 TI - In situ assessment of phytotechnologies for multicontaminated soil management. AB - Due to human activities, large volumes of soils are contaminated with organic pollutants such as polycyclic aromatic hydrocarbons, and very often by metallic pollutants as well. Multipolluted soils are therefore a key concern for remediation. This work presents a long-term evaluation of the fate and environmental impact of the organic and metallic contaminants of an industrially polluted soil under natural and plant-assisted conditions. A field trial was followed for four years according to six treatments in four replicates: unplanted, planted with alfalfa with or without mycorrhizal inoculation, planted with Noccaea caerulescens, naturally colonized by indigenous plants, and thermally treated soil planted with alfalfa. Leaching water volumes and composition, PAH concentrations in soil and solutions, soil fauna and microbial diversity, soil and solution toxicity using standardized bioassays, plant biomass, mycorrhizal colonization, were monitored. Results showed that plant cover alone did not affect total contaminant concentrations in soil. However, it was most efficient in improving the contamination impact on the environment and in increasing the biological diversity. Leaching water quality remained an issue because of its high toxicity shown by micro-algae testing. In this matter, prior treatment of the soil by thermal desorption proved to be the only effective treatment. PMID- 22046764 TI - Transgenic plants for phytoremediation. AB - Phytoremediation is a green, sustainable and promising solution to problems of environmental contamination. It entails the use of plants for uptake, sequestration, detoxification or volatilization of inorganic and organic pollutants from soils, water, sediments and possibly air. Phytoremediation was born from the observation that plants possessed physiological properties useful for environmental remediation. This was shortly followed by the application of breeding techniques and artificial selection to genetically improve some of the more promising and interesting species. Now, after nearly 20 years of research, transgenic plants for phytoremediation have been produced, but none have reached commercial existence. Three main approaches have been developed: (1) transformation with genes from other organisms (mammals, bacteria, etc.); (2) transformation with genes from other plant species; and (3) overexpression of genes from the same plant species. Many encouraging results have been reported, even though in some instances results have been contrary to expectations. This review will illustrate the main examples with a critical discussion of what we have learnt from them. PMID- 22046765 TI - [The true history of the first immortal cell lines of human origin]. PMID- 22046766 TI - [Cardiorenal syndrome]. AB - Cardiac and renal disease are common and frequently coexist, resulting in increased risk of mortality, morbidity and cost of care. The interaction between heart and kidney is refered to as cardiorenal syndrome, but a consensus definition has not been established. Also, there are limited data about the true incidence, the pathophisiology is poorly understood and standardized diagnostic criteria are lacking. Because the process is complex, treatment can be a challenge despite the novel therapies. This paper addresses all the complex interactive aspects of the cardiorenal relationship, from pathophysiology to epidemiology, diagnosis and treatment, to have more clear perspectives on the future therapeutic approaches to this deadly association. PMID- 22046767 TI - [Beta-lactamases...until when?]. AB - Due to environmental factors and wide use of antimicrobials, only those species that developed their own defense mechanisms shall survive. Enzymatic inactivation is the most common cause of antibiotic resistance. Beta-lactamase production has been described early after the discovery of penicillin and it continues to diversify being now able to inactivate even the most advanced antibiotic. The association with other resistance determinants makes the infection with this kind of bacteria a major therapeutic problem. PMID- 22046768 TI - [Clostridium difficile infections: what is new?]. AB - C. difficile is the most common infectious cause of healthcare-associated diarrhea but now is increasingly recognized as a cause of diarrhea in outpatients and persons without apparent health care contacts. Emergence and spread of new epidemic clones of C. difficile 027 (PCR-ribotype) and 078/126 (toxinotype) with increase toxin production, an aditional binary toxin and high level resistance to fluoroquinolones and increasing incidence of more rapidly progressive severe disease, require prompt clinical recognition and new tools to predict severity and to prevent recurrences. Although antibiotics are effective at inhibiting C. difficile and treating symptoms, these drugs could not reestablish normal bowel flora and the rate of recurrences is 25%. During the past years we assisted to an impressive search for new and more effective therapy that shoud be save, with low potential for the development of resistance, with low levels of systemic absorbtion and high levels of active drug in the colon and should be associated with a low rate of recurrence after treatment. By consequence, different approaches to the management of recurrent infections have been studied such as new antibiotics (fidaxomicin), human monoclonal antibodies against C. difficile toxins A and B, intravenous human immunoglobulin, active immunization, and probiotic therapy. PMID- 22046769 TI - Respiratory involvement in the gastroesophageal reflux disesease. AB - The pathological gastroesophageal reflux disease may lead to the gastroesophageal reflux disease (GERD), manifested as a spectrum of conditions including erosive esophagitis, Barrett esophagus and has been linked to the development of adenocarcinoma of the esophagus. The gastroesophageal reflux has been incriminated in the occurence of a number of pulmonary symptoms and diseases, otolaryngologic symptoms, and other extraesophageal manifestations. Clinicians must be aware of the possibility of some extraesophageal reflux-related manifestations, even in the absence of heartburn and acid reflux, classic esophageal symptoms of GERD. Although the correlation between gastroesophageal reflux disease and the extraesophageal manifestations has been established, a cause-and-effect relationship has not been proved yet. In this article, we present the respiratory manifestations of gastroesophageal reflux disease, referring to epidemiology, pathogenesis, diagnosis and treatment. PMID- 22046770 TI - [Contributions to the implementation of screening tests for assessing the neuropsychic development in children]. AB - Currently, in Romania the general practitioner does not use screening tests to detect the developmental problems in children. That might be the reason why many cases are diagnosed too late. AIM: To evaluate the impact and the usefulness of a screening tool for neurodevelopmental disorders in primary care. MATERIAL AND METHODS: This trans-sequential study was carried out a on a series of 324 children under the age of 5 in the interval January 2007-December 2010. The neurodevelopmental status of the children was assessed by two methods: routine clinical assessment, and ASQ screening tools. RESULTS: Compared to routine assessment, by which 33 children (10,2%) with development delays have been detected, the use of parent-addressed questionnaires raised the detection percentage to 12% (6 more children). The use of parent-addressed questionnaires also improved the doctor-patient communication, increased the degree of parental involvement in their child's development stimulation, especially with regard to the malfunctions in verbal and cognitive behavior. CONCLUSIONS: The use of validated screening tests is a goal for improving the primary care practice. PMID- 22046771 TI - [Liver cirrhosis--procoagulant stasis]. AB - Abnormal hemostasis tests and bleeding are often associated in liver cirrhosis. In these patients the balance between hypo- and hypercoagulation status is more fragile than in healthy people. In the hemostatic abnormalities associated with chronic liver disease are two main chategory factors: favoring hemorrage and favoring thrombosis. The main factors that favoring hemorrage are: low platelet count, impaired platelet function, decreased levels coagulation factors (II, V, VII, IX, X, XI), quantitative and qualitative abnormalities of fibrinogen, vitamin K defiency, low levels of trombin activable fibrinolisis inhibitor, activat plasminogenic tisular. The factors favoring thrombosis are elevated levels of factors VIII and von Willebrand, decreased levels of protein C, protein S, antithrombin, decreased levels of plasminogen. Traditionally it was thought that arterial and venous thrombosis is rare events in cirrhotic patients but recent studies have indicated that thrombotic complications can paradoxically occur even if clinically an increased risk of hemorrhage is considered. Treatment of venous thrombosis in patients with cirrhosis using routine anticoagulation with heparin and vitamin K antagonists has been described but with a high level of bleeding complications. So, based on the limited data available, AASLD guidelines stated no recommendations for or against the use of anticoagulation in cirrhotic patients with portal thrombosis. Although abnormal hemostasis tests and bleeding are often associated in patients with chronic liver disease it is a relatively poor correlation between hemorrhagic risk and routine diagnostic tests of hemostasis. Management of bleeding complications in liver cirrhosis varies and no general guidelines are available. The main therapeutic strategies are: red cell concentrate, plasma, platelet concentrate, recombinant factor VIIa, factor concentrates, desmopressin, antifibrynolitic agents, thrombopoietin receptor agonists, antibiotics. Clinical studies examining safety and efficacy of the various products for the different bleedeing or trombotic complications of liver cirrhosis need to be initiaded. PMID- 22046772 TI - Antibiotic prophylaxis considering patient outcome from percutaneous endoscopic gastrostomy. AB - OBJECTIVES: The main indications for PEG insertions are the following: stroke/CVA/diffuse cerebral vascular disease, neurological conditions, e.g. head injury, motor neurone disease, Multiple Sclerosis etc. Peristomal infection can sometimes complicate PEG placement. Antibiotics, either prophylaxis or concurrent, can reduce the incidence of peristomal wound infection after PEG placement. MATERIAL AND METHOD: Seventy five patients outcome from Percutaneous Endoscopic Gastrostomy (PEG) were analysed in the period: September 1999 and October 2007 to the West Cumberland Hospital, Whitehaven (WCH) United Kingdom. This paper was done to evaluate the practice in WCH and the outcome has helped us to implement the changes successfully to conform to the guidelines set out by the British Association of Gastroenterologists. Our main objectives were to evaluate the antibiotic prophylaxis, the procedure and post procedure complications and the deaths after PEG tube insertion. CONCLUSIONS: No immediate procedure complications; Infection was the most common postoperative complication; Antibiotics, either prophylaxis or concurrent, reduce the incidence of peristomal wound infection after PEG placement; Early PEG placement facilitates their transfer to a non-acute care environment. PMID- 22046773 TI - [Colorectal cancer--clinical course, epidemiologic and pathologic aspects]. AB - In the past 3 years colorectal cancer became the second cause death (after the broncho-pulmonary cancer) exceeding gastric cancer by 4150 deaths in 2002 (19,05 per hundred thousand inhabitants) and 4860 deaths in 2006. MATERIAL AND METHODS: 644 of the 18,978 patients coloscopically investigated at the lasi Gastroenterology and Hepatology Institute in the interval 2000-2007 in which pathology results revealed colorectal cancer, and 279 patients operated at the First Clinic Surgery of the Iasi "Sf. Spiridon" Hospital during 2008-2010 were selected for this study. RESULTS: Colorectal carcinoma has a high incidence in the patients over 60 years. Sex distribution of the tumors showed that this disease most commonly affects males. The male/female ratio was 1.3. In less than 3% of the cases the disease occurred at ages under 40 years. The most frequent clinical manifestations were intestinal transit disorder (97%), pain syndrome on the left side of the abdomen (82.82%), and progressive severe constipation (67.89%). 24.07% of the colorectal cancer cases were located at the level of the proximal colon (cecum, ascending colon, hepatic flexure, transverse colon and splenic flexure), while 75.9% were located at the distal level. The most frequent macroscopic form was the vegetative one (89.91%). PMID- 22046774 TI - [Cross-sectional study to evaluate risk factors in infant malnutrition]. AB - Malnutrition is a major health problem in our country by maintaining a high number of infants with poor nutritional status. Various studies have highlighted the role of infant's malnutrition in the development of adult diseases. METHODS: We made a cross-sectional study during six months (October 2010 - March 2011) on a group of 63 infants admitted in Pediatric Recovery Department-Children's Hospital, Iasi; we evaluated the presence of risk factors for malnutrition. The data were processed using SPSS 16 and Epilnfo 3.5.2. (December 2010). RESULTS: The infants were predominantly female (52,4%); the most affected age group was 5 24 weeks (84,11%). Most of them came from rural areas (79,4%), from families with low socioeconomic income (95,2%), mothers with a low educational status (63,4%), housewives (88,9%). We noted the presence of previous diseases in 71,4% infants. Only 12 infants received breast milk for a short time (three weeks), the other 51 infants have been bottle-fed since birth. Complementary food was incorrect in 68,42% cases. With a proper diet the mean weight gain was 895,68 g and the Z score values (weight for age, height for age, weight for height) have improved during an average of 34,15 days; positive correlation between these factors is strong. CONCLUSIONS: Low socio-economic income, rural areas, low maternal educational level, diet errors, small infants with multiple previous diseases are the main risk factors in malnutrition's occurrence. We consider particularly important to solve social problems too, not only the medical, because when the infant returns in the same disadvantaged family there is an increased risk for malnutrition to recur. PMID- 22046775 TI - [Correlations between anthropometric parameters and cardio-vascular risk factors related to lifestyle in a rural population]. AB - BACKGROUND AND AIMS: Prevention and reduction of cardio-vascular mortality are in relationship with understanding and being able to modify risk factors, among which overweight and obesity become the most significant. The aim of this paper is to define cardio-metabolic risk factors which are specific to the studied population, and also to find elements of lifestyle that lead to overweight. We targeted smoking, alcohol consumption, stress, physical exercise, income and educational level. MATERIAL AND METHODS: We studied a sample of 172 subjects, representative for the population of Deleni, a rural community in Iasi County; among these subjects, 67 were men, 105 were women, with an average age of 54. For each a chart was filled, containing demographic data, socio-economic status, personal and family medical history. We measured anthropometric parameters: weight (W), height (H), waist circumference (WC) and we calculated body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). We performed interviews to fill in a food frequency questionnaire, the Perceived Stress Scale and the International Physical Activity Questionnaire. RESULTS: In the lot studied, 44.2% are overweight and 18.6% are obese, the majority of these being women. Regarding WC, among normal weight, 52.4% have large WC (> or = 94cm for men and > or = 80cm for women). Obesity markers positively correlate with increase in age and decrease in income (p=0.024), with low educational level, regular consumption of coffee (p=0.093), and negatively correlate with excessive alcohol consumption (p=0.049) and smoking (p=0.003). As expected, there is an inverse relationship between increased physical exercise and BMI (p=0.015) and a direct relationship between increased stress level and WC. CONCLUSIONS: Anthropometric parameters are sensible markers in evaluating the influence of lifestyle on cardio-metabolic risk. PMID- 22046776 TI - [Etiological aspects of acute gastroenteritis--a ten-year review (1.01. 2001 31.12.2010)]. AB - Acute gastroentritis is one of the most common diseases in humans, and continues to be a significant cause of morbidity worldwide. AIMS: To determine the bacterial pathogens associated with gastroenteritis in patients admitted to the Iasi Infectious Diseases Hospital in the last ten years. MATERIAL AND METHODS: A total of 40481 stool samples were examined using conventional methods. RESULTS: Bacteria were found in 7.36% of cases, and parasites in 9.64%; 83% of the cases were viral, micotic, or disbiotic. The bacterial etiology was dominated by Salmonella spp. (58.34%), Shigella spp. (27.08%), Yersinia enterocolitica 03 (8.53%), Campylobacter spp. (1.31%), other bacterial pathogens (EPEC, Aeromonas hydrophilla/caviae/sobria, Plesiomonas shigelloides, Bacillus cereus, Staphylococcus aureus, etc) being detected in 3.74% of the cases. Of the Salmonella species, group B (51.99%) followed by group D (45.23%) were most common. Shigella sonnei and Shigella flexneri were found in almost the same proportion (49.45% and 49.70%, respectively); Shigella boydii was isolated in only 0.85% of cases. The trend of gastroenteritis caused by bacterial pathogens is decreasing: from 355 cases in 2001 to 105 cases in 2010; three peaks have been recorded in 2002, 2005 (when Salmonella typhi was isolated in a patient), and 2008 (469, 409, and 252 cases, respectively). Bacterial gastroenteritis affected both sexes almost equally (122 males and 118 females). The most affected age groups were: 0 - 4 years, 15 - 24 years, 5 - 14 years and 25 - 39 years. CONCLUSIONS: Laboratory investigations are essential in determining the etiology of gastroenteritis. Its unpredictable incidence justifies the human and material efforts aimed at controlling the spread of potentially epidemic acute gastroenteritis. PMID- 22046777 TI - [Monitoring of Mycobacterium tuberculosis infections in Iasi County in 2009]. AB - Tuberculosis is a major public health problem worldwide. Our study aimed to investigate epidemiological and demographic characteristics of tuberculosis infection and resistance to antituberculous drugs in Iasi County in 2009. MATERIAL AND METHOD: We have analysed the epidemiological parameters for 687 patients with pulmonary tuberculosis, new cases confirmed by microscopy and cultivation on Lowenstein Jensen. First and second-line antituberculous susceptibility testing was done for 130 strains, using agar proportion method and absolute-concentration method. RESULTS: The number of new cases of tuberculosis was higher in rural areas and in males 41-50 years old (sex ratio=2.22). The proportion of positive cases in microscopy was 81.51%. Drug resistance was as follows: 16 isolates (12.3%) to isoniazid, 5 (3.84%) to rifampin, 2 (1.53%) to ethambutol, 2 (1.53%) to streptomycin and 4 (3.07%) were multidrug-resistant. CONCLUSIONS: In this study we found high resistance rates to isoniazid, streptomycin and ethambutol. This requires increasing efficiency of tuberculosis diagnosis and susceptibility testing. PMID- 22046778 TI - [Bone mineral density in patients with rheumatoid arthritis]. AB - Patients with rheumatoid arthritis (RA), an immune-mediated inflammatory rheumatic disease with peripheral and systemic involvement, are at increased risk of bone loss and fractures. There are many reasons for the high prevalence of osteoporosis (OP) in RA, including both traditional and specific risk factors such as pain and loss of joint function, medication (corticosteroids, methotrexate), and increased proinflammatory cytokines. AIM: To evaluate bone mineral density status in RA patients, focusing on potential relation with classical risk factors for OP. MATERIAL AND METHODS: One-year prospective observational study on 83 consecutive postmenopausal women, 43 diagnosed with RA (group I), and 40 healthy controls (group II) with no previous condition and medication known to affect bone metabolism and turnover. Bone mineral density (BMD) and T-score evaluated by dual X-ray absorbtiometry (DXA) at three standard skeletal sites (L1-L4 lumbar spine, hip and forearm) (Hologique QDR 100 device), and classical risk factors for osteoporosis were assessed in all patients according to a predefined protocol. Data were analyzed in SPSS-13 using ANOVA, t Student, chi-square and ROC (Receiver Operator Characteristic). RESULTS: Decreased BMD was reported in the majority of RA cases, mainly in the spine and femoral neck (86%), but also in total hip (72%); moreover, osteoporosis was commonly demonstrated in lumbar spine and osteopenia at hip level. Statistically significant differences between diagnostic categories (normal, osteopenia, osteoporosis, WHO 1994) (p<0.05), while no significant differences between mean BMD levels in women with and without RA at different skeletal sites were found (t student, p>0.05). However, considerable BMD variation (51.7% to 102.3%) was suggested in RA as compared to non-RA patients (14.3% to 27%) (ANOVA). Significant differences in mean T-score at total hip and forearm (mainly 33% radius) were noted in patients with and without RA (p<0.05). No relation between osteodensitometric parameters and classical risk factors for OP has been identified in RA, except menopause. Indirect weak statistically significant correlations were found between mean T-score and menopause duration at all skeletal levels (Pearson's rank correlation, p<0.05), except for the femoral neck (r=+0.03, p<0.05). CONCLUSIONS: Decreased BMD is commonly seen in RA patients. Several characteristics based on DXA assessment have been identified, including preference for distinct skeletal sites (spine, hip, distal forearm), and the particular intervention of menopause. PMID- 22046779 TI - [Detection of fusion gene--integral part of the assessment of children with acute leukemia]. AB - Acute leukemia is the most common malignancy in children, being mostly produced by such chromosomal abnormalities as translocations or inversions causing gene fusion. Different clinical studies showed that translocations identified in ALL (acute lymphoblastic leukemia) and AML (acute myeloblastic leukemia) may be used to classify patients into risk groups. AIM: To detect three fusion genes that have been proven very important in patient classification: t(9:22)p190, t(4:11) and t(12:21). MATERIAL AND METHOD: We conducted a prospective study on 30 patients with acute leukemia diagnosed in the interval September 2009 - September 2010 at the Iasi Hemato-Oncology Unit of Saint Mary Hospital for Children. RESULTS: We found t(9:22)p190 in two patients, t(4:11) in two patients and t(12:21) in one patient. From the total of 30 patients, 7 were considered at high risk, 3 were diagnosed with AML, and 20 were considered at standard-risk. CONCLUSIONS: Day 33 can still be considered the reference time in the evaluation of treatment response; patients with BCR-ABL seem to have a worse prognosis than those who do not have this translocation. The detection of fusion genes is very important in patient classification. PMID- 22046780 TI - [Characteristics of hepatitis C virus (HCV) infection in closed communities]. AB - AIM: To determine the prevalence of HCV in closed communities and the relations between risk behavior and HCV infection. MATERIAL AND METHODS: The persons deprived of personal freedom selected for this study have filled out an epidemio logical questionnaire including identity and epidemiological data (detention history, evaluation of the risk factors), as well as a written consent. All the subjects were tested for the presence of anti-HCV antibodies. RESULTS: This study included 326 of the total of 500 persons deprived of personal freedoms at the Bacau Correctional Facility The prevalence of hepatitis B and C was 15.34 %, and that of HCV 5.21%, higher than in the general population. Risk factors associated with HCV in closed communities were injected drugs, homosexuality, and tattooing. CONCLUSIONS: The results confirm that the population in correctional facilities is at high risk for infection with hepatitis viruses (both B and C), the modes of disease transmission being already known. PMID- 22046781 TI - Methods for estimating "dry weight" in hemodialysis patients. AB - The correct estimation on dry weight is very important in providing effective and safe hemodialysis to end stage renal disease patients. Optimal fluid removal with minimal adverse reactions from the treatment is one goal of hemodialysis treatment. The aim of this article is to discuss different methods of assessing dry weight and to determine their role in the complex fluid management of end stage renal disease patient. Recent literature describes various methods of determining optimal hydration state, including clinical or paraclinical methods. Each of these methods has their benefits and limitations. Despite the large number of studies conducted on new technologies for determining dry weight, there is a lack of larger, randomized controlled trials to support these methods. Although the successful use of different methods of dry weight assessment is not supported yet by large clinical trials, some evidence is starting to link the use of some methods to improved outcomes (morbidity, mortality) in this population. PMID- 22046782 TI - [Relevance of L-type calcium channels for the non-genomic effects of estradiol and aldosterone upon contractile activity in isolated arteries]. AB - Non-genomic vascular effects of steroids are incompletely understood, despite progress made regarding some aspects, such as the mechanism of endothelium dependent relaxation by estrogens. AIM: To investigate the involvement of certain mechanisms in the rapid, non-genomic effects of estradiol (EST) and aldosterone (ALD) on endothelium-dependent and -independent vasomotor responses. MATERIAL AND METHODS: Isometric myography of rings from aorta, mesenteric arch, and first order mesenteric branches isolated from male Wistar rats was used. RESULTS: We found that L-type calcium channels (Cav1.2) are important for endothelium independent relaxation induced by EST, while ALD reduces the involvement of Cav1.2 in phenylephrine-induced contraction and potentates both NO- and EDHF mediated endothelium-dependent relaxation. To further examine the relevance of Cav1.2 for the vascular effects of EST and ALD, we were using rings with and without functional endothelium, precontracted by direct activation of Cav1.2 (Bay K 8644), high extracellular K+, phenylephrine, and under complete Cav1.2 block (nifedipine). Data suggest that EST, which directly inhibits Cav1.2 in transfected HEK cells, uses mainly this path to induce endothelium-independent relaxation, and that ALD may induce a rightward shift in the voltage-dependence of Cav1.2. PMID- 22046783 TI - [Improvement of genetic diagnostic strategy in velo-cardio-facial syndrome]. AB - Velo-Cardio-Facial Syndrome (VCFS) is characterized by congenital heart defects (CHD), palatal abnormalities, facial dysmorphism, neonatal hypocalcemia, immune deficit, speech and learning disabilities. SVCF is caused by microdeletion 22q11.2. Microdeletion is detected by fluorescence in situ hybridization (FISH). The highly variable phenotype makes diagnosis and selection for FISH more difficult. AIM: To retrospectively analyze and compare the phenotype of children with a clinical diagnosis of VCFS with/without 22q11 deletion; to verify the validity of literature guidelines and to describe combinations of clinical features that should lead to molecular analysis. MATERIAL AND METHODS: The present study was performed in 21 patients with a clinical diagnosis of VCFS. Methaphase chromosome spreads were prepared from phytohaemagglutinin stimulated lymphocyte culture by standard methods before FISH. The patients were divided into two groups according to FISH test: positive and negative. RESULTS: The features commonly noticed in FISH positive patients were: palatal abnormalities/hypernasal speech, learning disabilities, facial dysmorphism, tapered fingers (6/6), CHD (5/6) and recurrent infections (2/6). In FISH negative patients the following were found: learning disabilities, CHD (12/15); facial dysmorphism (10/15), family history of CHD (7/15), short stature (6/15), hypocalcemia, tapered fingers (5/15), recurrent infections (3/15) and palatal cleft (2/15). In both groups, Tobias and McDonald-McGinn guidelines were positive. CONCLUSIONS: VCFS has a highly variable phenotype. Our study suggests that 22q11.2 deletion analysis by FISH should be performed in patients who have at least 2 (newborn)/3 (child, adult) specific criteria: CHD, hypocalcemia, palatal abnormalities, facial dysmorphism, learning disabilities, digital anomalies, and immune deficit. PMID- 22046784 TI - [Descriptive assessments of a series of rheumatoid arthritis patients admitted to rehabilitation treatment between 2008 and 2010]. AB - AIM: To assess some demographic features in a series of 741 rheumatoid arthritis patients admitted to the Clinic Hospital of Rehabilitation at Iasi in different stages of disease in order to select the most adequate rehabilitation teratment. MATERIAL AND METHODS: Data were collected from patients' records, hospital statistical reports, and then processed and interpreted using EPI/INFO and MS Excel. RESULTS: Sex distribution revealed that the disease was more common in females (male/female ratio 0.2). The prevalence was higher after the age of 40, from 15.4% to 33.8% between 51 and 60, and 40.2% after 61. The most important comorbidities were related to osteoporosis (48.9%), ischemic cardiopathy and essential arterial hypertension (40.1%), impaired glucose tolerance and diabetes mellitus (36.9%), viral hepatitis B and C (24.02% of all cases). CONCLUSIONS: In selecting the most adequate rehabilitation treatment (drug therapy, kinetotherapy, and physical therapy) patient's age, and his various associated diseases have to be considered. PMID- 22046786 TI - [Metabolic syndrome in HIV-infected patients with favorable response to antiretroviral therapy]. AB - AIM: The assessment of the metabolic syndrome prevalence, as defined by the American Heart Association/The US National Cholesterol Education Program Adult Treatment Panel, (AHA/NCEP III updated), has been made in 68 polyexperimented HIV infected patients that received antiretroviral therapy over 24 months and who have a favorable viroimunologic response (undetectable plasmatic viral load). MATERIALS AND METHODS: this cross-sectional analytical study has been carried out on a cohort of 68 patients clinically and paraclinically monitored at the HIV/AIDS Department. RESULTS: The response to antiretroviral therapy clinically and paraclinically evaluated after two years from the initiation of the novel HAART scheme has been favourable in all the 68 patients. Only 4 (0.58%) of the patients fulfill the criteria of the metabolic sindrome definition. The statistical analysis does not indicate an increase in the risk of the metabolic syndrome development in these polyexperimented patients, where the clinical symptoms connected with the lipodistrophic syndrome with lipoatrophy are preponderent, associated with different types of antiretroviral drugs. CONCLUSIONS: The metabolic syndrome criteria are not applicable in the case of HIV infected patients (infected in the first year of life), polyexperimented at HAART therapy with favourable viroimmunologic response. PMID- 22046785 TI - [Aspects of the antimicrobial resistence profile in infections with Escherichia coli and Klebsiella pneumoniae in diabetic patients]. AB - Infections in diabetic patient remains an important cause of morbidity and mortality, triggering and maintaining a prolonged metabolic imbalance. Emergence of extented spectrum beta-lactmase (ESBL) in Escherichia coli and Klebsiella pneumoniae is a major concern, because of the atypical manner infection acts in this group of imunodepressed patients and also for the limited therapeutic solutions. For this reason we have evaluated the profile of antimicrobial resistance of these pathogens in both diabetic and non diabetic patients. MATERIAL AND METHOD: The aim of this study was to evaluate, in a retrospective case control study, the antibiotic susceptibility pattern in isolates of E. coli and Klebsiella spp. from different biological products in 49 diabetics and 150 non-diabetics admitted in The Clinical Hospital of Infectious Diseases Iasi over a period of two years. RESULTS: Most of strains of E. coli and Klebsiella spp. ESBL positive were found in uroculture. Significant differences in E. coli resistance rate between diabetics and nondiabetics were noted for amoxicillin clavulanic acid and ciprofloxacin (31,4% vs.13,98%, p=0,04, respectively 52,9% vs. 24,46%, p=0,004). More isolates of ESBL positive K. pneumoniae were found in diabetic patients (50% vs. 24%). Ciprofloxacin resistance of K. pneumoniae was significantly higher in diabetics (75% vs 39%; p=0,05). There was no resistance in E. coli and K. pneumoniae isolates to imipenem in the diabetic group. CONCLUSIONS: The high resistance rate to quinolones and 3rd generation cefalosporins limits their use for the treatment of Escherichia coli and K. pneumoniae infections. Other alternatives for empiric therapy in community and nosocomial-acquired infections in diabetic patient remains carbapenems, aminoglycosides and colimycin. PMID- 22046787 TI - Diagnostic approach of pneumonia in an elderly patient with comorbidities--case report. AB - Dyspnea is one of the symptoms that has a major impact on patients' health, with a negative influence on the quality of life. The main causes of dyspnea are cardiac, pulmonary and mixed (cardiac or pulmonary). There are several other causes such as metabolic conditions (acidosis), pain, neuromuscular disorders, otorhinolaryngeal disorders, anxiety, panic disorders and hyperventilation. Acute pneumonia in the elderly is a common occurrence and its incidence grows as the elderly population increases. We report the case of a 76 years old patient with a known cardiovascular condition, recently hospitalized for right pulmonary infarction. He presented to our clinic for influenced general state, rest dyspnea, fever, shiver, and productive cough in the last two days. Current medication included oral anticoagulants and triple antihypertensive treatment (responsible for his low blood pressure). Laboratory results showed a nonspecific inflammatory syndrome with leukocytosis and neutrophilia and mild normochromic normocytic anemia; D-dimers were within normal range, fibrin degradation products 1+; myocardial enzyme testing showed no alteration, and BPN (beta natriuretic peptide) was 790 pg/ml. Chest X-ray showed diffuse bilateral reticular shadows (more pronounced on the right side) and left costodiafragmatic opacification. It appears that age-related increase in morbidity and mortality in community acquired pneumonia is not due to age per se, but to interactions between the immune system, systemic diseases and nutritional factors. Community-acquired pneumonia in the elderly is known to have a high mortality. Although the diagnosis can be easy, the physician must also investigate for less obvious causes of dyspnea such as the presence of comorbidities and fragility of the elderly patient. PMID- 22046788 TI - [Toxic cause febrile neutropenia]. AB - Agranulocytosis is an acute disease with severe leucopenia, especially with low neutrophils, elements with an essential role in the organism's defense. It is more frequent at adult age (between 30 to 70 years of age) especially in women. We present the case of a 84 years old patient that, following passive exposure to pesticides, develops a severe neutropenia with a fast response to the administration of Methylprednisolone and granulocyte colony-stimulating factor (G CSF-Filgrastim 48MIU/0.8mL/day, for three days). The diagnostic certainty was set by the bone marrow puncture which excluded a possible aleukemic acute leukemia or a myelodysplastic syndrome. PMID- 22046789 TI - The prognosis of posterior urethral valves, associated to vesicoureteral reflux in children. AB - Posterior urethral valves represent a congenital barrier at the level of the posterior urethra, which opposes miction. They are located near the prostatic urethra, originating at the verumontanum level, affecting male patients. The ureters are inconstantly dilated; vesicoureteral reflux is met in 2/3 of the cases. The reflux can be secondary to the sub-bladder barrier, but it can also be considered primitive, determined by the intra bladder ectopy of the ureter. The presence of the reflux is interpreted as a severe associated factor. Semiology is rather unusual, positive diagnosis is based on early discovery or antenatally of the impairment, by fetal echography starting from the 28th week of pregnancy, postnatal echography followed by miction cystography, retrograde urethrography and creatinine dosage complete the diagnosis. The treatment is surgical: endoscopic ablation of the valves (in the absence of renal failure), percutaneous pyelostomy, high lateral ureterostomy, and in severe cases vesicostomy and renal transplant. Prognosis depends on how early the impairment is detected, on the degree of pulmonary hypoplasia, on the presence of the vesicoureteral reflux and the possibility of recovering renal function; 1/3 of the newborns develop in time Chronic Renal Failure which requires renal transplant. The studied group comprised male children diagnosed with vesicoureteral reflux their ages ranking between 0 -18 years, admitted to the Pediatric Clinic, Tg. Mures during the last 10 years and children diagnosed and operated with posterior urethra valves at the Surgical Clinic of the "M. S. Curie" Hospital, Bucharest during the last 20 years. Our results show that out of the total number of studied children 25 presented posterior urethra valves and 9 children presented vesicoureteral reflux. We can conclude that the presence of the vesicoureteral reflux is an unfavorable prognosis regarding the degree of renal failure. PMID- 22046790 TI - [Industrial sound spectrum entailing noise-induced occupational hearing loss in Iasi industry]. AB - In European Union every day millions of employees are exposed to noise at work and the risk this can entail. AIM: this study presents the sound spectrum in Iasi heavy industry: metal foundries industry, punching and embossing of metal sheets, cold and hot metal processing. MATERIAL AND METHODS: it was used a type 2 Sound Level Meter (SLM) and the considered value was the average value over 10 test values in 10 consecutive days for each octave band in common audible frequency range. RESULTS AND DISCUSSIONS: It is obviously that the large values of sound intensities in the most of frequency octave band exceed maximum admissible and legal values. CONCLUSIONS: The study reveals the necessity of hardware, medical and managerial measures in order to reduce the occupational noise and to prevent the hearing acuity damage of the workers. PMID- 22046791 TI - [Sinonasal headache--reality or mis-diagnosis?]. AB - Facial pain can be the presenting, and sometimes the only, complaint of many disorders that originate from cranial structures. One causes of facial pain/headache is sinusitis, in both its acute and its chronic presentation. Successful management of headache is preceded by the identification of an etiology and precise diagnosis. MATERIAL AND METHODS: A prospective study was carried out on a series of 71 patients treated in the ENT Department of Iasi "Sf. Spiridon" Hospital between January and august 2009 for pathology implying facial pain, headache, facial pressure, nasal obstruction, rhinorrhea. The therapy was medical and surgical and pursued nasal desobstruction, sinusal drainage and ventilation. Data regarding different parameters were analyzed pre and post therapy. RESULTS: After the proper treatment for each situation, the parameters analyzed improved significantly, although, in some cases the main accuses regarding the pain remained unchanged or slightly ameliorated. CONCLUSIONS: Depending on the clinical suspicion of the possible etiologies of facial pain and headache, the appropriate consultations should be made. For concerns of head and neck lesions or sinus-related headache, an otolaryngologist should be consulted. If a primary headache syndrome or a cranial neuralgia is of concern, the patient should be evaluated by a neurologist. Dentists and oral surgeons should be involved. In some cases, a psychiatry referral is appropriate. The surgical treatment can be effective if the pathology meets the criteria of sinonasal facial pain. PMID- 22046792 TI - [Borderline ovarian tumors and global radiation in relation with climate change impact]. AB - There is limited information on borderline ovarian tumor detected intra surgically and its most favorable treatment in relation with global radiation and climate changes. AIM: To study the pre-surgery and intra-surgery differentiation criteria of borderline ovarian tumors from invasive carcinoma, and to make a very complex analysis of the frequency, distribution, and variation in time of global radiation, temperature, and precipitation in North-East Romania. MATERIAL AND METHOD: The 54 patients (age range 20-78 years, mean age 46 years) included in this study had borderline ovarian tumors surgically treated during the last 22 years (January 1988 - December 2009) at the 4th Gynecological Clinic at Iasi, and representing 4.87% of the total 1107 ovarian tumors detected and treated during this interval. The histological types were: serous (18 cases), mucinous (27 cases), mixed (8 cases), and Brenner tumor (1 case). In order to analyze the impact of climate changes on borderline ovarian tumors a thorough study on the frequency of global radiation in relation with climate changes based on data recorded in the last 55 years was also carried out. RESULTS: The distribution of these cases depending on when surgery was performed was analyzed. In our study the frequency of ovarian borderline tumors (4.87%) is lower than in similar reports in the literature being due, in our opinion, to the influence of global radiation in relation with climate changes. CONCLUSIONS: In our study global radiation is probably responsible for a progression to invasive carcinoma in 0.7% of the borderline ovarian tumors. PMID- 22046793 TI - [Parapharyngeal space--history and surgical study]. AB - One area of anatomy, which is a true passage of secrecy, is the anatomy of the potential anatomical spaces. The study of the fascial layers of the head and neck and the potential spaces they make-up is both fascinating and confusing. Much of the confusion is a function of the multiple synonymous terms and classifications that various authors use, and not the basic anatomical description. Their anatomy and communications, to the base of skull and downward to diaphragm, acts like a route through which infection from mouth and throat can reach the superior mediastinum. CONCLUSIONS: Understanding the anatomy of the parapharyngeal space is important in making a correct diagnosis and surgical plan for removing tumors in this region. PMID- 22046794 TI - [Binaural cochlear implant--good choice in the treatment of deep sensorinural hearing loss]. AB - Nowadays. cochelar implant is the only choice of treatment in deep bilateral deafness. AIM: To evaluate the benefits of binaural implantation of a single receiver-stimulator device by using audiometric tests at 3 and 6 months intervals. MATERIAL AND METHODS: The study included 3 patients with bilateral sensorineural deafness of cochlear origin. Following implantation they were assessed by pure tone audiometry (PTA), speech audiometry (SA), and sound localization tests (LT). RESULTS: PTA showed a significant decrease in hearing thresholds level during the 6-month interval following implantation. As to the degree of speech discrimination in both quiet and noisy environment, SA showed evident progress at 6 months compared to the results at 3 month. The location tests revealed improved sound localization in both ears at 6 months compared to the results at 3 months. CONCLUSIONS: Compared to unilateral implant, the binaural cochlear implant has the advantage of stereophonic hearing, facilitating the communication through a better understanding of speech in both quiet and noisy environment, and improving the quality of life by the location of sounds similar to natural hearing. PMID- 22046795 TI - [Expression of hormonal receptors (alpha-estrogen, beta-estrogen, progesteron), Ki-67 and P53 in endometrium of tamoxifen treated breast cancer patients]. AB - Tamoxifen is the most commonly prescribed adjuvant therapy for women with breast carcinoma ER+. It has agonist activity on the endometrium and is associated with an increased risk of endometrial carcinoma. The aim of this study was to evaluate the immunohistochemical changes on the histological endometrial modification from the patients treated with tamoxifen. MATERIAL AND METHOD: A group of 20 women selected from 125 patients with breast carcinoma, with adjuvant therapy. The criteria of selection were the histopathological proliferative changes of endometrium from these symptomatic patients. The 20 specimens of endometrium were evaluate immunohistochemycal by estrogen receptor alpha, beta, progesterone receptor, Ki-67 and P53. RESULTS AND CONCLUSIONS: The 20 endometrium specimen showed histological proliferative endometrial lessions, including polyps, hyperplasia and carcinoma. Immunohistochemical, benign lessions showned expression of estrogen alpha and beta receptor, low expression Ki-67 and absent expression of P53. These tests were negative in clear cell carcinoma, but were intens positive for Ki-67 and P53. In general, tamoxifen associated endometrial adenocarcinoma were characterized by a lower expression of estrogen receptor alpha, higher expression of progesterone receptor, and more frequent expression of estrogen receptor beta than endometrial spontaneous tumors. PMID- 22046796 TI - [The lymph nodes status--prognostic factor in breast cancer]. AB - AIM: The assessment of the survival rate according to axillary lymph nodes status in patients diagnosed with breast cancer. MATERIAL AND METHODS: The study group included 206 women, treated in the 4th Obstetrics and Gynecology Clinic during 2002-2005. All patients were treated surgically with lymph nodes dissection. The analyzed variables included clinical and morphological features of both primary tumor and axillary lymph nodes. We have evaluated 5 years survival in relation to positivity and number of dissected lymph nodes. In order to determine the prognostic value of evaluated variables we have used Kaplan Meir method. RESULTS: 77.7% of all patients were aged between 40 and 49 years old and 62.6% of them presented stage II tumors. Invasive ductal carcinoma was the most frequent histologic type (79.12%) and 71.2% of tumors were moderated of poorly differentiated, lymph nodes invasion being presented in 93 cases. Survival was significantly influenced by lymph node status (p = 0.0001), number of involved nodes (p = 0.0001), number of dissected nodes in pN0 patients (p = 0.0001) and application of adjuvant systemic therapy in pN0 patients (p = 0.0001). CONCLUSIONS: The pathological examination of axillary nodes in breast cancer patients offers a valuable information regarding survival. The absence of lymph node metastases of 10 lymph nodes dissection or more, and the application of adjuvant systemic therapy favorably influence the survival. PMID- 22046797 TI - [Incidence of congenital malformations in the Iasi "Cuza Voda" Maternity Hospital]. AB - AIM: To update the data on the incidence of congenital malformations in our area and emphasize the importance of prenatal diagnosis. MATERIAL AND METHODS: The study was conducted over a period of ten years and included 2211 cases with congenital malformations. Such parameters as the incidence of malformations over these years, gestational age at the moment of diagnosis, and mortality from congenital malformations were followed. Statistical and graphical data were processed with the help of SPSS 16.0 and MS Excel software. RESULTS: The total prevalence of malformations was 3.52%, comparable with the data in the literature. Over this period a number of 262 cases (11.8%) ended in spontaneous miscarriage or termination of pregnancy for fetal abnormalities. A significant percentage of these pregnant women gave birth to their child, many of them dying shortafter. CONCLUSIONS: Congenital malformations remain the leading cause of mortality in neonates. In Romania, the advanced techniques of prenatal diagnosis being used only in specialized centers, and a large number of cases may escape early diagnosis. This study underlines the importance of a correct assessment of fetuses so that the discovery of fetal abnormalities at birth not to be a surprise. PMID- 22046798 TI - [Functional reeducation of flexor tendons with associated lesions in zone II- comparative study]. AB - Regaining satisfactory digital function after flexor tendon laceration and repair has long been one of the most important problems in hand surgery. But optimal therapy is often difficult to ascertain, given the plethora of immediat postoperative protocols published in the scientific literature. AIM: The purpose of this study is to compare the functional results between Kleinert, Silfverkiold, Gratton and Strickland protocol towards evaluate them by interconnection and with the literature. MATERIAL AND METHODS: The prospective study enorolled 75 patients who presented in our cabinet consecutives during 1.05.2008-1.12.2010. The subjects were evaluated regarding Total active motion test and Grip strenght test at 12 weeks postoperative. RESULTS: We found the best results to Gratton group, followed by Strickland, Silfverkiold-May and Kleinert groups. CONCLUSIONS: We conclude that, for the tendinous lessions with associated injury (nervs and vessels) in zone II, our first therapeutical indication is to use the Gratton protocol. PMID- 22046799 TI - [Rare clinical situatons of the diverticuli of the colon]. AB - It is well known that the diverticuli of the colon gets inflamed in 10-15% of cases, thus becoming clinical symptomatic as a diverticulitis, while in other 15% they will bleed, with the clinical aspect of an inferior digestive bleeding. Our study presents some clinical observations with diverticuli of the colon, that raised diagnostic and therapeutic problems. MATERIAL AND METHOD: Between 2001 2010, 17 patients were admitted in the 3rd Surgery Clinic, University Hospital "St.Spiridon", Iasi, with asymptomatic diverticuli of the colon, that were put in evidence imagistically, intraoperative or on specimens after removal of the colon for other conditions;meanwhile, there were 15 patients admitted with complications of the diverticuli:5 patients had perforated diverticulitis (4 pericolic abscesses and one with peritonitis in the lower abdomen), 4 had rectal bleeding and the other 6 raised particular problems of diagnostic and treatment, being included in the present study. RESULTS: Five out of six underwent operation. One patient refused the surgical treatment. Postoperative evolution was favorable in 4 out of the 5 operated patients. CONCLUSIONS: The complications of colonic diverticuli present on admission under clinical aspects that usually mimic a colonic cancer. In these situations the imagistic examinations do not offer enough details to elucidate the diagnosis. Our six particular observations strengthen the dictum of avoiding the "mirage" of the first lesion. The extent of the surgical procedure in the case of patients with colonic diverticuli admitted under the clinical aspect of a complication is sometimes disproportionate and encumbered of increased mortality and complication rate. PMID- 22046800 TI - Biocompatibility testing of chitosan hydrogels. AB - Chitosan is a linear, natural cationic polysaccharide comprising beta-1,4 linked glucosamine and N-acetyl-D-glucosamine. Hydrogels of chitosan were prepared by crosslinking with varying amounts of glutaraldehyde. It can be used as a bacteriostatic, fungistatic and coating agent, and the gels and suspensions may play the role of carriers for slow release or controlled delivery of drugs, as an immobilizing medium and an encapsulation material. MATERIAL AND METHODS: Chitosan and glutaraldehyde were used to prepare the hydrogels and their characteristics were investigated by Fourier transform infrared (FT-IR) spectroscopy and the inhibitory effect on cellular growth was tested by chemiluminescence assay. The hemolytic activity was also determined by direct contact with human blood and the concentration of hemoglobin was spectrophotometrically measured. RESULTS AND DISCUSSION: Chitosan hydrogels have no inhibitory effect on cell growth, and hemolytic action below 1%, which means good blood compatibility; therefore they are promising materials. PMID- 22046801 TI - [The influence of stress factors on liver function and lipid metabolism in an animal model of arterial hypertension]. AB - AIM: to investigate the influence of some stress factors on hepatic function and lipid metabolism in an experimental-induced hypertension. MATERIAL AND METHODS: The experiment was carried out on Wistar rats, treated intraperitoneally, for 4 weeks, as follows: Group 1: saline solution (0.5ml/100g weight); Group 2: saline solution + stress; Group 3: Endotelin-1; Group 4: Endotelin-1 + stress; Group 5: Endotelin-1 + cholesterol diet (0.2g/kbw/day); Group 6: Endotelin-1 + cholesterol diet + stress. Endotelin-1 0.25nmol/kbw was initially administered, followed by 0.5nmol/kbw 15 min later, 2 times/week. Stress-inducing factors were immobilization and water immersion. In the 28th day of the experiment blood pressure was measured and blood samples were taken from retro-orbitary plexus to assess glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lactic dehydrogenase (LDH) activity, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides levels. RESULTS: Using immobilization and water immersion as chronic stress, our study proved an increase of GOT, GTP and total and LDL cholesterol in rats with endotelin-1-induced hypertension. CONCLUSIONS: In this animal model of endothelin-1-induced hypertension the blood pressure increased significantly under chronic exposure to stress, reaching the highest values when associating stress and experimentally induced dyslipidemia. PMID- 22046802 TI - [Experimental research regarding the influence of the stress factors in an animal model of HELLP syndrome]. AB - AIM: to study the effects of licht/dark induced-stress in an animal model of HELLP syndrome. MATERIAL AND METHODS: The experiment was carried out on white female Wistar rats treated intraperitoneally, for 4 weeks, as follows: Group 1: saline solution 0.5ml/100g weight; Group 2: saline solution + dark induced stress, continuously, 28 days; Group 3: saline solution + light induced-stress, continuously, 28 days; Group 4: endotelin-l; Group 5: endotelin-1 + dark induced stress, continuously, 28 days; Group 6: endotelin-1 + light induced-stress, continuously, 28 days. Endotelin-1 0.125nmol/kbw was initially administered, followed by 0.25nmol/kbw 30 min later, 2 times/week. RESULTS: At the end of the experiment blood pressure was measured and blood samples were taken to assess: leukocyte formula, phagocytic capacity of peripheral neutrophils and serum complement activity, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and lactic dehydrogenase (LDH) activity, total bilirubin and lipid profile. CONCLUSIONS: In these experimental conditions we obtained an animal model of partial HELLP syndrome (elevated liver enzyme levels and a low platelet count, values emphasized by light induced-stress, without hemolysis). In chronically stressed animals we found the highest levels of blood pressure, a decrease of plasmatic cortisol level and of phagocytic capacity of peripheral neutrophils and an increase of total cholesterol. PMID- 22046803 TI - [Assessment of some biophysical parameters of human erythrocyte by FT-IR spectroscopy--preliminary study]. AB - Based on the biochemical composition of erythrocyte membrane and asymmetric distribution of phospholipids, proteins, and cholesterol, FT-IR spectroscopy can monitor the distribution and interaction pattern of membrane constituents. MATERIAL AND METHODS: The study series included 21 clinically healthy subjects aged between 20 and 60 years. Complete blood counts were performed and the serum biochemical compounds (cholesterol, triglycerides, total protein, glucose) were determined. RESULTS AND DISCUSSIONS: The parameters that can be assessed by erythrocyte FT-IR in relation with the biochemical factors that may influence membrane fluidity are: degree of fatty acids unsaturation, saturated fatty acids/unsaturated fatty acids ratio, cholesterol/phospholipids ratio, and phospholipids/protein ratio. Based on the obtained results, in the assessment of membrane status the following vibration modes were selected as spectral parameters: vibration associated valence bond (=CH), asymmetric valence CH2 groups, modes associated with P=O bond and amine bands I and II specific for proteins. Other parameters, such as v(C-O) specific to glucose, may provide additional information on glucose metabolic status. CONCLUSIONS: By correlating biochemical markers with these spectral parameters information on red cell membrane status, status that may reflect different pathological processes, can be obtained. PMID- 22046804 TI - [Contributions to the assessment of hemodynamic status in metabolic syndrome]. AB - The concept of normohemodynamics is based on the fact that the main function of the cardiovascular system is the transport of oxygen. The cardiovascular system is adapting to a new hemodynamic status with every heartbeat. Only one class, called the normohemodynamic state, containing a simultaneous normotension and normodynamic flow, can serve as therapeutic goal. Metabolic syndrome includes a constellation of clinical and biological features that confer an increased cardiovascular risk. Clutter hemodynamic modulators in metabolic syndrome and assessment of hemodynamic status both overall and by its components, open new perspectives in the management of patients with hypertension and metabolic syndrome. MATERIAL AND METHODS: In the current study were included 32 patients meeting the criteria for metabolic syndrome and hypertension and 32 controls. Patients were monitored and assessed for the global hemodynamic status and for the modulators of hemodynamics, intravascular volume, vasoactivity and inotropy, respectively. RESULTS AND CONCLUSIONS: There are no significant differences in the global hemodynamic status between the study group and the control group; in the study group there is a clear weathering of hemodynamic modulators. The improvement of these factors opens a new perspective in the global cardiovascular assessment and therapeutic directions. PMID- 22046805 TI - [Morphopathological changes in glaucoma-induced trabecular meshwork]. AB - Glaucoma causes trabecular meshwork and Schlemm canal changes, resulting in the obstruction of the aqueous flow at this level. AIM: To show the histological changes in the surgically removed trabecular meshwork tissues. MATERIAL AND METHOD: Trabecular meshwork fragments were histologically processed for histological diagnosis. RESULTS: 29.87% of all patients had ordered structure with high eosinophilia, 20.12% a rare structure with high eosinophilia, 21.34% a voluminous trabecular meshwork with fusiform cells, 21.03% tissue fibrosis and 7.62% had tissue necrosis. CONCLUSIONS: Aqueous flow obstruction in trabecular meshwork is produced by the histological changes at this level, found in all tissue specimens removed during surgery. PMID- 22046806 TI - [Experimental research on the effects of a Cetraria islandica extract on oxidative stress in laboratory animals]. AB - AIM: Experimental researches on the effects of a Cetraria islandica extract, with or without magnesium association, on oxidative stress in rats. MATERIAL AND METHODS: The experiments were carried out on Wistar rats, treated intraperitoneally for 14 days at single daily dose as follows: Group 1: Saline solution (SS) (0.5 ml/100g bw/day); Group 2: Subcutaneous pellets, SS; Group 3: Levamisole (LEV) (10mg/kbw/day); Group 4: Subcutaneous pellets, LEV; Group 5: Prednison (PDN) (5mg/kbw/day); Group 6: Subcutaneous pellets, PDN; Group 7: MgSO4 (5mg/kbw/day); Group 8: Subcutaneous pellets, MgSO4; Group 9: C. islandica (Ci) extract (21.56mg/kbw/day); Group 10: Subcutaneous pellets, Ci; Group 11: Ci+MgSO4; Group 12: Subcutaneous pellets, Ci+MgSO4. At the end of the experiment blood samples were collected for assessing the following oxidative stress parameters: malonaldehyde, catalase, glutathione peroxidase, glutathione levels. RESULTS: In the rats with or without experimentally-induced granuloma, repeated administration of Ci for 14 days resulted in a decrease of malonaldehyde, catalase, glutathione peroxidase activity, and an increase in glutathione levels. The association of magnesium augmented the antioxidant effect of Ci in this experimental model. CONCLUSIONS: In our study experimental conditions C. islandica extract determined adaptogenic-antistress effects, confirmed by its actions on oxidative stress parameters. PMID- 22046807 TI - [Epidemiological observations on survival in the first year after acute ST elevation myocardial infarction (STEMI) treated by primary angioplasty]. AB - Conditional analysis of survival factors after acute myocardial infarction is important in care practice. We analyzed the survival and occurrence of coronary ischemic events during the first year after the episode of acute myocardial infarction with ST segment elevation (STEMI). We prospectively evaluated at one month and one year the patients with STEMI assisted in November 2008 - February 2010 at Heart Institute "Niculae Stancioiu" with primary coronary angioplasty (ACP) performed during the first 12 hours of the onset of pain. We analyzed statistically survival and occurrence of ischemic events. Survival rate was 95.6% (CI95%: 92.7 to 97.3) at one month and 92.1% (CI95%: 87.8 to 94.2) ate one year after STEMI. Survival was significantly reduced in anterior STEMI (83.4%), history of ischemic heart disease (83.4%), stroke (81.2%), females (81.8%) and ischemia exceeding > 6 hours (83.6%). The rate of ischemic events avoidance was 96.5% (CI95%: 0.938 to 0.980) at one month and 81.7% (CI95%: 76.7 to 85.6) at one year after STEMI. The ischemic events, as evaluated through avoidance rate of phenomena, were significantly more frequent in females (69.9%), dyslipidemic (72.9%), hypertensive (73.7%) patients, having history of ischemic heart disease (72.4%) and total ischemia time longer than 6 hours (70%). Evolution of patients with STEMI after ACP is significantly better in patients with non-anterior location, males, without history of coronary disease, stroke, hypertension, dyslipidemia, ischemic time > 6 hours. PMID- 22046808 TI - [Clinical epidemiological study of acute gastro-enteritis outbreak recorded in a children community, in Iasi, May, 2009]. AB - Acute diarrheal disease affect all demographic structures and it is considered a major cause of morbidity and mortality for young age groups; underreporting is due to clinical and epidemiological diversity, everywhere, including the developed countries. MATERIAL AND METHODS: The authors present an epidemic outbreak of acute gastroenteritis by rotavirus in a community of 240 children. Processing and interpretation of collected data was done by statistical, mathematical and computerized methods. RESULTS: A number of 17 cases of acute gastroenteritis caused by rotaviruses were detected and confirmed, mostly in children older than 5 years (92%), with a tendency to focus on large group "A", 40%. All cases showed mild forms evolving medium. CONCLUSIONS: The 17 cases of infection with rotaviruses were the second episode of acute gastroenteritis with the same etiology, reported over two months. Extensivity of the epidemic outbreak was moderate, with the predominant age group affected over six years (58%). Developing and implementing preventive measures included daily cleaning and decontamination standards. PMID- 22046809 TI - [Study about the associated use of different types of drugs by high school students]. AB - Socially acceptable drugs and illegal substances consumed by high school students affect their nervous system, which is under development and anticipate an extensive drug use later. MATERIAL AND METHOD: In our study we have assessed the associate drug consumption at a group of high school teenagers by applying a questionnaire with 23 items. RESULTS AND DISCUSSION: Tobacco use is the lowest in ninth grade students and it is significantly better represented in higher grade students. Regardless of the grade, there are no significant differences in the proportion of boys and girls who smoke, even the health risks posed by smoking are known to over 80% of respondents. Among the reasons that could cause the student smoking cessation predominates, at the smallest students, parents' threat (significantly stronger than at those of senior grades), unlike the senior students, which give a higher value to a possible alteration of their own health status. The temptation for beer consumption appears before the age of 11 years and it is mentioned about a quarter of all respondents. Drinking a glass of wine for the first time is placed around the age of 14 years for boys and 15 years for girls. Marijuana is the drug exclusively consumed in the ninth grade and holds supremacy and other classes. Barbiturates and amphetamines are known about two thirds of the surveyed students. Risks involved by the association of alcohol consumption, tobacco and drugs are represented differently in this group of adolescents, and evolve differently as the students grow, mature and evolve, in a positive manner for their existence or not. CONCLUSIONS: during the high school years teenagers are tempted to diversify their drug consumption and to associate them, even they know very well how serious are the health consequences of this attitude. PMID- 22046810 TI - [Use of real time PCR for testing Staphylococcus aureus isolates from the Iasi Infectious Diseases Hospital]. AB - S. aureus is capable of producing a wide spectrum of diseases and can quickly develop resistance to antibiotics. These features require a careful monitoring of these organisms, by detection of resistance genes and virulence factors, such as Panton-Valentine leukocidin (PVL). AIM: To determine the presence of mecA and pvl genes in S. aureus isolates by a Real Time-PCR technique (RT-PCR) in order to shorten the detection time. MATERIALS AND METHODS: We tested 119 strains isolated from pus, using phenotypic methods for methicillin resistance characterization, according to CLSI 2008-2010 guidelines. Detection of mecA and pvl genes was done with hydrolysis probes. RESULTS: The prevalence rate of methicilin resistant S. aureus (MRSA) was 40,33%, and pvl was detected in 52,08% of those strains. The results of the conventional methods for methicillin resistance detection were validated by those obtained by RT-PCR CONCLUSIONS: RT-PCR is useful in epidemiological surveillance of MRSA and PVL-producing strains and validation of test results for phenotypic resistance to oxacillin. PMID- 22046811 TI - [Assessment of the congenital syphilis prevention programs]. AB - The Romanian program for the management and screening of syphilis includes the recording, follow-up, and antenatal care of pregnant women. It aims at testing all pregnant women for syphilis with the help of VDLR (Venereal Disease Research Laboratory) or RPR (Rapid Plasma Reagin) tests, and in the women with positive tests to confirm the results by treponemal tests (treponemal antibodies): THPA (Treponema Pallidum Hemagglutination), FTA-Abs (Fluorescent Treponemal Antibody with Absorption), ELISA-Captia-IgM, and Western Blotting-IgM. In the pregnant women with positive tests two doses of 2.4 million units of penicillin G benzathine were administered at 5 days interval. These pregnant women are in the evidence of a specialist (obstetrician, dermatologist), and District Department of Public Health, and required to come for another serology test in 3 months. In case they still test positive, the same treatment is applied at the beginning of the third trimester of pregnancy. AIM: To assess the outcome of congenital syphilis prevention programs in lasi, Romania. MATERIAL AND METHODS: In the interval 2005-2011, in the Iasi town, 84 RPR positive pregnant women were recorded. There was no significant difference in the number of pregnant women residing in urban as compared to rural areas. Most of these women were from poor social environments and had a low level of education. The diagnosis of acquired syphilis was made by serological tests as most pregnant women presented in the period of syphilis latency, being asymptomatic. All pregnant women followed the treatment, and were tested periodically. Ultrasound examination was normal in all women (no changes suggestive of fetal malformations). RESULTS: Free clinical, laboratory, and ultrasound investigations, history taking, psychological assessment, sex education, rapid identification of contacts of known patients, follow-up of the interaction between health care providers and syphilitic pregnant women, booklets, and leaflets altogether made that in the last 3 years (2008-2010) no new case of congenital syphilis to be reported in the study area. CONCLUSIONS: Encouraging women to attend antenatal care early in their pregnancy is essential, this way all pregnancy-related problems (syphilis included) could be managed. PMID- 22046812 TI - [Dental treatment strategies for elderly patients]. AB - The elderly are influenced from a various and complex combination of factors, such us individual genetic predispositions, lifestyle, society and environment, the sum of all the individual life experiences concerning the dental care, the caries, the periodontal and iatrogenic diseases. AIM: This paper evaluates the dental treatment in the elderly. MATERIAL AND METHODS: The study was performed on 112 patients, aged over 65, at the Clinical Department of Dental Semiology und Geriatric Dentistry, Iasi, Romania. RESULTS: The treatment interventions were dental hygiene procedures (in 97 patients), restaurations (in 29 patients), removable partial and total denture preocedures (in 50 patients), fixed prosthetic procedures (in 18 patients), rebasing of dentures (in 25 patients) and teeth extractions (in 26 patients). There were 36 endodontic emergencies and 15 periodontal emergencies and 8 emergencies that resulted from other causes. CONCLUSIONS: The periodical dental examinations and the proper daily oral hygiene routine are still important in the old age and they should not be neglected, because the prosthetical components request also treatment interventions. PMID- 22046813 TI - Endodontic retreatment in case of failure. Case report. AB - In medical practice, clinicians come across an increased number of endodontic treatments, which, like other dental treatments, can fail. The increase in the number of endodontic treatment resulted in an increased number of failures, their management raising complex and serious endodontic problems. The endodontic retreatment of a failure is required by the increased desire to preserve the tooth on the dental arch, thus preventing the need for dental extraction that may have adverse consequences in terms of functional and psychological effect on patients. This article presents two clinical cases that required endodontic retreatment in order to avoid the complications that could ultimately require tooth extraction. The teeth in question (a mandibular first molar and an upper central incisor) having a special importance, and a physiognomic role, the endodontic retreatment consisted in covering them in porcelain fused to the metal crowns. PMID- 22046814 TI - Pharmacokinetic modeling of glimepiride plasma concentration in healthy subjects. AB - AIM: To determine the pharmacokinetics of glimepiride, a sulfonylurea antidiabetic agent, after single dose administration in healthy subjects. MATERIAL AND METHODS: Pharmacokinetic data for modeling were extracted from a single-center, randomized, single-dose, fasting state, two-way crossover bioequivalence study on 4 mg glimepiride in 24 healthy subjects. RESULTS: Plasma concentrations of glimepiride were measured using a validated LC/MS/MS method. The pharmacokinetic parameters were calculated using non-compartmental analysis. Different pharmacokinetic models were tested to evaluate pharmacokinetics of glimepiride. The optimal model was chosen based on Akaike's Information Criteria. CONCLUSION: Compartmental analysis demonstrated that oral glimepiride tablets obey one compartment open model with rapid absorption following a first order kinetics and a short half-life. PMID- 22046815 TI - [Interactions between oral anticoagulants and other medication in emergency department--a pharmacoepidemiologic approach]. AB - Oral anticoagulants (OAC) are commonly used as a life-long therapy in the prevention of systemic embolism in patients with atrial fibrillation, valvular heart disease, prosthetic heart valves, and in the primary and secondary prevention of venous thromboembolism, in patients with acute myocardial infarction and angina pectoris. Drugs, herbs, and multivitamin supplements can alter the absorption, pharmacokinetics or pharmacodynamics of OAC. AIM: To investigate the possible interactions between oral anticoagulants and different drugs administered in patients in emergency department. METHODS: This 1-year exploratory investigation on 93 patients on OAC (aged 30 - 85 years), admitted at two emergency departments of the Iasi "Sf. Spiridon" Hospital and Piatra Neamt Hospital, consisted in their medical records analysis: diagnosis, recommended treatement. Data were scored and statistically analyzed by t-test (Windows Excel). The experimental protocol was in agreement with the recommendations of the Gr.T. Popa University Committee for Research and Ethical Issues. RESULTS AND CONCLUSIONS: Analysis and statistical processing of data shows that during the study period 56 patients which received oral anticoagulant therapy associated with different other medication belonged to the 60 and 80 years age group. This finding suggests that the pathology is represented especially by atrial fibrillation and myocardial infarction. The correlation between the therapy consisting in OAC and sartan or nonsteroidal anti-inflammatory drugs and International Normalized Ratio (INR), revealed a high level of anticoagulation and an increase in hemorragic complications. PMID- 22046816 TI - [Semi-quantitative determination of methadone by TLC]. AB - Methadone is the main therapeutic option in heroin addiction treatment, but also an abuse substance. Given the analytical focus on the diagnosis of drug abuse and the usefulness of toxicological analysis methods in both overdose and monitoring substitution therapy, this study was aimed at the semi-quantitative determination of methadone by using Thin Layer Chromatography (TLC). By having the advantage of simplicity and rapidity, TLC finds its rightful place among the analysis methods when other relatively costly methods that involve instrumental performance are not available. MATERIALS AND METHODS: TLC plates (silicagel GF 254 Merck), developing system methanol: strong ammonia 100: 1,5, photometric quantification at 254 nm, using TLC Scanner 3 (Camag). RESULTS: The results show that methadone can be determined semi-quantitatively in the chromatographic conditions mentioned in the two domains tested (5 - 40 microg and 10 - 80 microg), with the best results obtained in the 5 - 40 microg domain. CONCLUSIONS: Semi-quantitative TLC evaluation proposed by us has as main advantages the rapidity, simplicity and relatively low cost compared to other useful methods. PMID- 22046817 TI - [Antimicrobial activity of some cinnamic acid derivatives]. AB - Due to drug-resistance phenomenon, there is a constant need for discovering new antiinfectious agents. A series of cinnamic acid derivatives was synthesized and then brominated with bromine in the presence of chloroform or acetic acid. The structure of the new compounds was confirmed by elemental and spectral data. Their antimicrobial activity was tested by disc-diffusion method. The tested compounds had mainly antifungal activity and were moderately active against Gram positive bacteria. Bromination of the double bond determined the enhancement of the antimicrobial activity for all the tested compounds. PMID- 22046818 TI - [Research for the improvement of acylation conditions in antistaphylococcal penicillin synthesis]. AB - AIM: The 6-aminopenicillanic acid acylation with certain acyl chlorides was performed in order to obtain antistaphylococcal penicillins with bigger crystals, easy to filtrate (shorter filtration time), much pure, and an increased output. MATERIAL AND METHODS: Oxacillin sodium salt was synthesized by acylating an aqueous solution of 6-aminopenicillanic acid sodium salt (NaHCO3 not in excess) with an ethylacetate solution of 5-phenyl-3-methyl-isoxazolyl-4-carboxilic acid chloride. The crystallization was performed with a 40.5% sodium 2-ethyl hexanoate izopropanolic solution. All tests (IR spectrum, iodometric titration, and microbiological dosage) were performed according to the Xth Romanian Pharmacopoeia standards. RESULTS: The amount of synthesized oxacillin was higher and the output of 88,21%. Oxacillin had a high chemical purity (98,72%), and a very good microbiological activity (95% of the standard activity). CONCLUSIONS: Oxacillin crystals were bigger, the filtration speed was increased, and process efficacy improved. The output of the process was also improved being higher than with classical acylation. PMID- 22046819 TI - [Comparative study of some clinical and laboratory indicators in a group of patients using wells as source of drinking water and a control group using safe water]. AB - In time, well water, as a source of drinking and coking water, with physical chemical, bacteriological, and biological indicators suggestive of alteration in water potability, determines complex, sometimes irreversible, metabolic disorders. MATERIAL AND METHODS: Sixty individuals residing in a rural community were divided into 2 groups: study group -30 subjects using well water, and control group--30 subjects using safe water. For the study group the selection criteria were: age, sex, use of well water as drinking and cooking water, history suggestive of chronic poisoning (pregnancy course, birth weight, susceptibility to infectious agents, and current chronic diseases). RESULTS: In the study group, gestosis, prematurity, and altered body mass index are more frequent as compared to the subjects in the control group. The identified laboratory changes indicate moderate anemia, hepatic cytolysis, dyslipidemia, presence of nitrites in urine, and positive urine cultures. CONCLUSIONS: Long-term use of water with mineral constituents in excess, absent, or inadequate, the direct biological and chemical water pollution, or most frequently the indirect pollution through the soil determine, in time, complex, sometimes irreversible, metabolic disorders. PMID- 22046820 TI - [The use of vascular prothesis Gore Viabahn in the managment of the lower limbs ischemia]. AB - The chronic lower limbs ischaemia is caused mainly by arteriosclerosis. After insufficient conservative treatment only the surgical intervention can salvage the limb. The revascularisation surgery can be performed by open surgery with implantation of the prosthetic bypass or by endovascular angioplasty with stent. This second method seems to be the best alternative for the patients with several concomitant systemic diseases. Nevertheless it is limited by presence of the long distance arteriosclerotic lesions. The resolve of that problem is use of new generation of long endovascular covered stents. They can be succesfuly used in aorto-femoral and femoro-popliteal segment. Their efficiacy is simmilar to traditional prosthetic grafts. PMID- 22046821 TI - [The operations of the abdominal hernias with the use propylene material in patients operated due to abdominal aortic aneurysm]. AB - The correlation between abdominal hernias and aortic aneurysm has been well documented in literature. The pathophysiology of aneurysm and hernia formation is seen within the abnormal collagen metabolism, resulting in extracellular matrix defects. This study presents a group of 8 men in the age of 36 to 78 years old (average 63, 5 years old) who underwent both an operation for the aneurysm and for the abdominal hernia. Of the reported 8 patients, 7 had postoperative hernias, where 4 of the cases there were recurrent postoperative hernias. The remaining patient had an inguinal hernia. In 7 cases patients underwent an abdominal aortic aneurysm (AAA) operation and in one case a hepatic artery aneurysm endovascular operation was performed. Due to the fact that postoperative hernias are an immense problem, especially within the group of patient with collagen defects, the area of research and improvement of the materials that are used in prosthetic hernia surgery today needs to progress. This study also presents a short review of the various types of prosthetic materials used in the production of hernial meshes. This is to emphasize the necessity of improving operational techniques to minimize the risk of herniation, especially within a group of patients with collagen defects. PMID- 22046822 TI - [Use of synthetic mesh in abdominal wall hernias repair]. AB - Abdominal hernias repair beside cholecystectomy and appendectomy is the most commonly performed surgical procedure. The crucial problem in surgery treatment of abdominal hernias is its recurrence, especially high in procedures performed without use of synthetic graft. Advances in understanding the etiopathogenesis of abdominal hernias and the introduction of the new surgical techniques have considerably improved the results of its repair. The widely used synthetic mesh is made of durable material and its structure enables easy and safety intraperitoneal implantation also in laparoscopic surgery. Unfortunately the high cost of this procedure limits its use. There is still need for 'ideal' mesh material and high hope for increasing biological graft application in the future. PMID- 22046823 TI - [Use of polymeric clips in laparoscopic appendectomy]. AB - The aim of this study was to evaluate efficiency and safety of using non absorbable polymeric clips in securing the stump of appendix during laparoscopic appendectomy. PATIENTS AND METHODS: We have analyzed patients of Surgical Clinic of 4th Military Clinical Hospital in Wroclaw, who underwent laparoscopic appendectomy from 2006 to 2010. Patients were divided into 3 groups regarding to the way of securing stump of appendix: in group one non-absorbable polymeric clips Hem-o-lok were used, in group two endostaplers Endostapler Flexi and in group three endoloop ligatures or traditional ligatures. Evaluated data included operative time, intra- and postoperative complications, hospital stay and costs of used materials. RESULTS: There were performed 90 laparoscopic appendectomies between 2006 and 2010 in Surgical Clinic of 4th Military Clinical Hospital in Wroclaw. Non-absorbable polymeric clips Hem-o-lok were used in 30 patients, endostaplers in 27 and endoloop ligatures in 33 cases. There were no intra- and perioperative complications such as bowel injury, appendix stump leak or early bowel obstruction. Two cases of postoperative pericaecal (perityphlic) abscess (1 in group one, 1 on group two) were observed, in both cases antibiotic therapy was successive, patients didn't require surgery. Wound infection was observed in 3 cases (2 in group one, 1 in group three). Mean operative time was 70,5 min. in group one (from 40 to 115 min.), in group two 58,5 min. (from 25 to 110 min.), and in group three 76,3 min. (from 40 to 120 min.). Mean hospital stay was 2,6 days in group one (from 2 to 4 days), in group two 2,9 days (from 2 to 7 days.), and in group three 2,88 days (from 2 to 8 days). CONCLUSIONS: Using of non absorbable polymeric clips Hem-o-lok is an efficient and safe way of securing the stump of appendix during laparoscopic appendectomy, comparing to other methods (endostapler and Endoloop ligature). Advantages of polymeric clips are facility of application (most of surgeons have experience in clips application during performed for many years laparoscopic cholecystectomies) and low cost (comparing to endostaplers). PMID- 22046824 TI - [Analysis of antibiotic diffusion from agarose gel by spectrophotometry and laser interferometry methods]. AB - The aim of this study was to analysis of antibiotics (ampicilin, streptomycin, ciprofloxacin or colistin) release from agarose gel by spectrophotmetry and laser interferometry methods. The interferometric system consisted of a Mach-Zehnder interferometer with a He-Ne laser, TV-CCD camera, computerised data acquisition system and a gel system. The gel system under study consists of two cuvettes. We filled the lower cuvette with an aqueous 1% agarose solution with the antibiotics at initial concentration of antibiotics in the range of 0.12-2 mg/ml for spectrophotmetry analysis or 0.05-0.5 mg/ml for laser interferometry methods, while in the upper cuvette there was pure water. The diffusion was analysed from 120 to 2400 s with a time interval of deltat = 120 s by both methods. We observed that 0.25-1 mg/ml and 0,05 mg/ml are minimal initial concentrations detected by spectrophotometric and laser interferometry methods, respectively. Additionally, we observed differences in kinetic of antibiotic diffusion from gel measured by both methods. In conclusion, the laser interferometric method is a useful tool for studies of antibiotic release from agarose gel, especially for substances are not fully soluble in water, for example: colistin. PMID- 22046825 TI - [The effect of the composition of stomatological dressings on Carbopol 971P and methylocelullose base on pharmaceutical availability of metronidazole]. AB - The carried out studies allowed to propose composition of stomatological dressing makes opportunity to ensure preferable physiochemicals features for dosage forms. According to results formulations contain 1.5% Carbopol 971P, 0.13% methylocelullose and various quantity of glycerol, 1,2-propylene glycol and polyethylene glycol 400 were prepared. To compare formulation consists of only polymers dispersion (Carbopol 971P and methylocelullose) was prepared. Next to produced compound triethanoloamine to pH range 5.5-6.5 and 1% metronidazole added. Kinetics test of metronidazole release was performed in vitro using Hanson's cells and semipermable membrane. The quantity of the release metronidazole was determined by spectrophotometric method. Gel consists of 98% polymers dyspersion with 2% glycerol characterized by the largest pharmaceutical availability. The addition of 2% PEG 400 resulted in the decrease of the percentage of released substance in comparison to formulation without hydrophylisers. Metronidazole releasing was more efficient for dressings with 2% glycerol as well propylene glycol. For preparations contains glycerol (2 and 5%) as well propylene glycol as adiuvants, it was found that gels prepared on Carbopol 971P and methylocelullose revealed higher pharmaceutical availability than analogical dressings prepared with only one polymer base. PMID- 22046826 TI - Extraction characterization and evaluation of selected mucilage as pharmaceutical excipient. AB - Natural polymers have been used in different pharmaceutical formulations. They are easily available, non-toxic, biodegradable and cost effective to be used as pharmaceutical excipient. In present investigation mucilage was extracted from fruit of Hibiscus esculentus and further characterized to be used as pharmaceutical excipient. Tablets were prepared using four different concentrations (6.6%, 13.3%, 20%, 26.66%) of Hibiscus esculentus mucilage and potato starch to evaluate binding properties of mucilage. Results obtained from the micromeritic characterization and flow behavior showed that Hibiscus esculentus mucilage is a good candidate to be used as pharmaceutical excipient. Tablets prepared using mucilage showed relatively lesser friability than prepared with starch. It was found that release of drug from tablets prepared with mucilage was less as compared to prepared with starch. Findings of the different results easily predict the fact that mucilage obtained from Hibiscus esculentus has characteristics to be used as pharmaceutical excipient. PMID- 22046827 TI - Preparation, characterization and application of chitosan-alginate based polyelectrolyte complex as fast disintegrating drug delivery carrier. AB - AIM: Present investigation was carried out with aim to synthesize chitosan alginate polyelectrolyte complex, their characterization and then formulation of phenytoin sodium fast dispersible tablet using polyelectrolyte as active excipient. METHODS: In this study, polyelectrolyte complex was formed by ionic cross-linking of polymers. Dried complex was evaluated for micromeritic properties and flow behaviour. Tablets were prepared for six batches based on different proportion of complex viz 5%, 10%, 20%, 30%, 40%, 50% and 60%. Tablets were evaluated for hardness, friability, thickness, in vitro disintegration time, in vitro dissolution study and stability study. RESULTS: Results of micromeritic study and flow behaviour predict that complex can be used as an efficient excipient. Hardness, friability, thickness all were in acceptable limit. Release studies were showed that tablets release drug up to 99.97%. Batch showed .sec of invitro disintegration time. Stability study easily predicted that formulation characteristics dose not changed during the whole period of study. CONCLUSIONS: From the findings it is concluded that chitosan-alginate polyelectrolyte complex is efficient excipient for fast dispersible formulation especially required in case of epilepsy and chronic diseases. PMID- 22046828 TI - [Density form of Kedem-Katchalsky equations for non-electrolyte solutions]. AB - A method of transformation of the Kedem-Katchalsky equations from concentration to density form was presented. These equations were applied for mathematical description of the volume flux (J(v)) through polymeric membrane in concentration polarization conditions, i.e. in existence on both sides of the membrane of concentration boundary layers (l(l), l(h)). Obtained model is the cubic equation, in which coefficients contain the membrane transport parameters (L(p), sigma, omega), density of solutions (rho(l), rho(h)), diffusion coefficients in layers (D(l), D(h)) and thicknesses of l(l) and l(h). Assuming that the layers l(l) and l(h) are symmetric (delta(l) = delta(h) = delta) and coefficients D(l) and D(h) are not dependent on concentration, the suitable transformation of model for J(v) the square equation for delta was obtained. PMID- 22046829 TI - [Modification of the Katchalsky's relation between effective and real solute permeability coefficients through polymeric membrane]. AB - Using Kedem-Katchalsky equations, in which volume (J(v)) and solute (J(s)) fluxes are functions of the osmotic (delta(pi)) and hydrostatic (deltaP) driving forces, the mathematical model for zeta(s) parameter was elaborated. This parameter describes relation between effective and real solute permeability coefficients through a membrane. Calculations performed on the basis of obtained quadratic equation show that for a polymeric membrane with fixed transport properties parameter zeta(s) is nonlinear function of solution concentration. This nonlinearity is caused by a change of distance between a system and stable state of diffusion. The reason of this nonlinearity is change of distance between a system and stable diffusion state. The appearance of instability related with breaking of symmetry of concentration boundary layers relative to the gravitation direction causes increases of the coefficient value. This is the sign of appearance of diffusion-convection of mass transport. PMID- 22046830 TI - [Dyspnea, what is the cause? Rhabdomyosarcoma]. PMID- 22046831 TI - [Physician office preemption should help reduce oversupply. Practice purchase by national health insurance is not necessarily a loss]. PMID- 22046832 TI - [Drugs, diabetes, nutrition, operations: in elderly patients much is different]. PMID- 22046833 TI - [When muscle strength declines in the elderly: prescribe sports and body building food!]. PMID- 22046834 TI - [Therapy of Hodgkin lymphoma: chances of remission are good, treatment tolerance needs improvement]. PMID- 22046835 TI - [Emergency in general practice]. PMID- 22046836 TI - [Emergency management in general practice]. PMID- 22046837 TI - [Experiences with functional neural therapy]. PMID- 22046838 TI - [Therapy of moderately severe depressions in daily practice: first patient care research study reinforces clinical data]. PMID- 22046839 TI - [Rhinitis during pregnancy]. PMID- 22046840 TI - [Hypothyroidism as a rare cause for pericardial effusion in a growth-restricted 18-year-old]. PMID- 22046841 TI - [Atrial fibrillation--a complication in hypertension]. PMID- 22046842 TI - [Nocturnal enuresis]. PMID- 22046843 TI - Health care provider tobacco cessation counseling among current African American tobacco users. AB - Tobacco use is the leading cause of preventable mortality and morbidity in the United States. Patients advised to quit use of tobacco products by their health care providers are more likely to quit, yet it has been documented that patients are not receiving this advice. The aim of this study was to investigate whether or not current African American tobacco users were receiving provider-initiated advice to quit. A cross-sectional survey identified 245 self-reported African American tobacco users residing in Maryland. Study variables collected included sociodemographics, access to care, smoking status, and assessed if tobacco cessation counseling was ever provided. Among those surveyed, only 42% reported ever being counseled to quit tobacco use and, of those who had a recent clinical encounter (within the past year), only 20% reported being counseled. Multivariate logistic regression identified that having a regular source of health care, living in an urban setting, and being female increased chances of being advised to quit tobacco use. Overall, findings indicate that African Americans are not being screened or receiving cessation counseling as recommended by leading health agencies. Health care provider training to promote better integration of tobacco screening and tobacco cessation counseling during the patient encounter is needed. PMID- 22046844 TI - Perceptions of colorectal cancer among three ethnic subgroups of US blacks: a qualitative study. AB - Colorectal cancer (CRC) is currently associated with one of the highest burdens of morbidity and mortality among American men and women. Racial/ethnic disparities are well documented and the subject of intense research and intervention. Our understanding of disparities related to awareness and perceptions about causes, risk factors, and screening for CRC among subgroups of blacks in the United States is limited. This may be in part because grouping US born blacks and foreign-born blacks as one homogeneous group obscures possible within-group differences. This study aimed to explore the cultural perceptions of CRC among 3 ethnic subgroups of blacks: African Americans (US born), foreign-born blacks from English-speaking Caribbean countries, and Haitian-born blacks. The study was informed by a community-based participatory research approach, using a cross-sectional mixed qualitative and quantitative methods design. A total of 62 individuals from the 3 ethnic subgroups participated in semistructured, in-depth qualitative and structured quantitative interviews. Qualitative findings revealed no stark differences among the 3 ethnic subgroups in their overall perceptions of cancer as well as their attitudes related to barriers, motivation, and resources for CRC screening. However, there were subtle differences in perceptions of curability, preventive practices, and preferred sources of information among the three ethnic subgroups of US blacks. The study has important implications for the design of educational materials and targeted interventions for diverse groups of US blacks. PMID- 22046845 TI - Screening adherence for colorectal cancer among immigrant Hispanic women. AB - PURPOSE: We sought to assess factors related to colorectal cancer (CRC) screening adherence among immigrant, Hispanic women in Harlem, New York City. METHOD: Adherence for colonoscopy and fecal occult blood test (FQBT) screening was measured among 255 women based on self-reported screening behaviors using American Cancer Society guidelines. RESULTS: Univariate results showed that age, language of the interview (English/Spanish), years in the United States, physician recommendation for either test, marital status (living alone/living with someone), and mammography adherence were associated with CRC screening adherence (p's < .05). In the multivariate analysis, having an age greater than 65 years, being interviewed in Spanish, having lived in the United States longer, having a regular doctor and a physician recommendation, and being currently adherent for mammography were associated with higher CRC screening adherence. CONCLUSION: Among this sample, there proved to be differences between having ever been screened and adherence with a greater proportion of women having ever completed either colonoscopy and/or FOBT compared to women who were adherent (72.9% vs 58.8%). Therefore, it is important to determine factors associated with adherence, not just screening utilization, in order to design strategies to increase adherence among immigrant Hispanic women. PMID- 22046846 TI - Smoking and cancer: a review of public health and clinical implications. AB - The cultivation of tobacco dates backwards to 6000 BC. Use of tobacco for spiritual, euphoric, and medicinal purposes, and its ultimate spread to the 4 corners of the globe, lay at the heart of the current pandemic of tobacco-related disease, including lung, head and neck, and many other forms of cancer. While evidence for the carcinogenic properties of tobacco was documented as early as the 1800s, it was not until the 20th century that the role of tobacco use and smoke exposure in the growing pandemic of lung and other cancers was fully appreciated. The evidence is now indisputable, and current research and intervention activities center on mechanisms by which tobacco use and smoke cause cancer, ways of stemming the worldwide pandemic of tobacco-related disease, and how to help people with cancer quit smoking. With respect to the latter, approaches to smoking cessation that are effective for the general population of smokers are equally applicable to cancer patients, thrusting physicians and other health professionals to the forefront of the antismoking arena. However, the scale of the tobacco pandemic has grown so large that it literally will take a village, complete with heads of nations, world-governing bodies, local leaders, physicians, and many others, to pass and enforce legislation and policies necessary to stem the worldwide tobacco pandemic and to implement cessation programs for smokers and users of other forms of tobacco across the globe. PMID- 22046847 TI - Patients' barriers to receipt of cancer care, and factors associated with needing more assistance from a patient navigator. AB - BACKGROUND: Racial minorities have poorer cancer survival in the United States compared to whites. The purpose of this study was to better understand patients' barriers to cancer care and to determine which patients have a greater need for assistance from a patient navigator. METHODS: Community health workers assisted newly-diagnosed breast and colorectal cancer patients during a randomized trial of patient navigation and collected information about patients' barriers. Barriers to care were characterized and compared between non-Hispanic white and minority patients. A multivariate model was constructed of factors associated with increased log navigation time, a measure of patients' need for assistance. RESULTS: Patients' (n = 103) most commonly identified barriers to care included a lack of social support, insurance/financial concerns, and problems communicating with health care providers. Barriers differed between nonminority and minority patients, and minority patients faced a greater number of barriers (p = .0001). In univariate analysis, log navigation time was associated with race/ethnicity, education, income, employment, insurance type, health literacy, marital status, language, and comorbidity. A multivariate model (R2 = 0.43) for log navigation time was created using stepwise selection, and included the following factors: minority race/ethnicity (p = .032), non-full-time employment (p = .0004), unmarried status (p = .085), university center (p = .0005), and months in study (p <.0001). CONCLUSIONS: Newly diagnosed cancer patients' most common barriers to care include lack of social support, insurance/financial concerns, and problems with health care communications. In this sample of patients, a greater need for assistance was independently associated with minority race/ethnicity and unemployment. These data may help in the design and targeting of interventions to reduce cancer health disparities. PMID- 22046848 TI - Urban/rural patterns in receipt of treatment for non-small cell lung cancer among black and white Medicare beneficiaries, 2000-2003. AB - BACKGROUND: Receipt of treatment for lung cancer varies by a number of demographic factors, including race/ethnicity and urban/rural residence. We examined urban/rural patterns in receipt of treatment for non-mall cell lung cancer (NSCLC) (ie, surgery, chemotherapy, radiation therapy) among black and white Medicare beneficiaries in Alabama. METHODS: After linking Alabama State Cancer Registry data with state Medicare data, we identified 3481 cases of stages I to IV and unknown-stage NSCLC diagnosed from 2000-2002 and obtained their treatment data for 1999-2003. We used bivariate and multivariate analyses to examine racial and urban/rural differences in receipt of treatment. Significant bivariate associations were tested using chi2 tests. RESULTS: Among beneficiaries with resectable NSCLC (ie, stages I-IIIA), urban whites were more likely to undergo surgical resection than urban blacks (49.3% vs 33.0%, respectively), and more rural whites than rural blacks (49.8% vs 23.9%, respectively) underwent surgery. There was less variation by race and urban/rural residence in the receipt of chemotherapy and radiation therapy. After controlling for age at diagnosis, gender, stage at diagnosis, comorbidity score, and socioeconomic status, the racial disparity for surgery remained. Black beneficiaries in urban counties had 45% lower odds of undergoing surgery than urban white beneficiaries (OR, 0.55; 95% CI, 0.31-0.96), and those in rural counties had 67% lower odds of receiving this treatment than their white counterparts (OR, 0.33; 95% CI, 0.19 0.57). CONCLUSIONS: Differences in receipt of surgery exist for both urban and rural black Alabamians with NSCLC. Future studies should explore access to care and perceptions about treatment among lung cancer patients in this state. PMID- 22046849 TI - Cervical cancer screening among ethnically diverse black women: knowledge, attitudes, beliefs, and practices. AB - This is a descriptive study of cervical cancer screening knowledge, attitudes, beliefs, and practices among ethnically diverse black women. We conducted 6 focus groups with Haitian, African, English-speaking Caribbean, and African American women recruited from a federally qualified health center. Overall, there was limited knowledge and confusion across ethnic groups about cervical cancer and its risk factors, the Pap test, and the human papilloma virus (HPV) and its association with cervical cancer. At the same time, there were distinct differences between ethnic groups in knowledge, practices, and cultural beliefs about cervical cancer. African women knew the least among all the groups, while African American participants had the greatest knowledge of HPV. However, their knowledge was still limited. Patient-doctor relationship was the single most important facilitator for cervical cancer screening. Barriers to cervical cancer screening included cost, busy work schedule, fear of the unknown, lack of insurance or being unemployed, and fear of disclosing immigration status. Interventions with ethnically diverse black women would benefit from recognizing cultural barriers and misconceptions that vary by ethnic group. Culturally based strategies suggested by the focus groups include the use of existing social networks, the use of indigenous community-based health workers, and the inclusion of women of all ages in cervical cancer education because of the roles they have in extended families. PMID- 22046850 TI - Strategies used and challenges faced by a breast cancer patient navigator in an urban underserved community. AB - Patient navigation has been widely implemented by cancer care programs across the United States. While activities of navigators have been described elsewhere, little has been documented regarding specific strategies used or challenges experienced by navigators from their own perspectives. We describe the experience of an African American patient navigator who promoted breast cancer screening and facilitated diagnosis and treatment among inner-city mostly African American women in Newark, New Jersey. We conducted qualitative analysis of journal notes, log data, and in-depth interviews with the patient navigator. Strategies used by the patient navigator to develop trust and rapport included: (1) "meet patients where they are" (outreach is best performed in locations women frequent, such as hair salons); (2) being accessible (must be flexible and available by phone or in person to meet patient's needs); and (3) "bring it down, sista" (must have "street credibility" in dress and language). Key challenges included experiencing threats to safety, setting boundaries, and facing and overcoming burnout. The patient navigator responded to these obstacles by creating new community linkages and resources and reaching out for emotional support from her mother and supervisor. Areas that need to be addressed further for future patient navigator programs include promoting safety in potentially dangerous neighborhoods and helping navigators set boundaries and avoid burnout. Further research into experiences of patient navigators in different settings is needed to build upon this preliminary data, and to consider character traits and attributes best suited for a patient navigator, as well as the support needed for this new health care worker. PMID- 22046851 TI - A cluster randomized controlled trial to increase breast cancer screening among African American women: the black cosmetologists promoting health program. AB - BACKGROUND: African American women have disproportionately higher rates of breast cancer mortality than all other ethnic groups, thus highlighting the importance of promoting early detection. METHODS: African American women (N = 984) from San Diego, California, participated in a randomized controlled trial testing the efficacy of breast cancer education sessions offered in beauty salons. Cosmetologists received ongoing support, training, and additional culturally aligned educational materials to help them engage their clients in dialogues about the importance of breast cancer early detection. Posters and literature about breast cancer early detection were displayed throughout the salons and cosmetologists used synthetic breast models to show their clients how breast cancer lumps might feel. Participants in the control group received a comparable diabetes education program. Baseline and 6-month follow-up surveys were administered to evaluate changes in women's breast cancer knowledge, attitudes, and screening behaviors. RESULTS: This intervention was well received by the participants and their cosmetologists and did not interfere with or prolong the client's salon visit. Women in the intervention group reported significantly higher rates of mammography compared to women in the control group. Training a single educator proved sufficient to permeate the entire salon with the health message, and salon clients agreed that cosmetologists could become effective health educators. CONCLUSIONS: Cosmetologists are in an ideal position to increase African American women's breast cancer knowledge and adherence to breast cancer screening guidelines. PMID- 22046852 TI - Barriers to colorectal cancer screening among publicly insured urban women: no knowledge of tests and no clinician recommendation. AB - OBJECTIVES: To assess barriers to colorectal cancer screening among urban publicly insured women and to evaluate how barriers among underscreened urban women have changed between 2001 and 2007-2008. METHODS: Eligible women were selected using Medicaid Managed Care Organization (MMCO) administrative data. MMCO outreach staff interviewed women by phone between October 2007 and February 2008, and assessed their barriers to colorectal cancer screening. We compared the results of these interviews with interviews conducted in 2001 with women in community health center waiting rooms. RESULTS: Thirty percent of overdue women had never heard of either colonoscopy or sigmoidoscopy, and 55% had never heard of home fecal occult blood testing (FOBT). Among overdue women who had heard of colonoscopy or sigmoidoscopy, 33% reported misconceptions and 28% reported worry as a barrier. No clinician recommendation was the most commonly reported barrier to home FOBT (44%) and was also reported as a barrier to endoscopy by 22% of women. Between 2001 and 2007-2008, the proportion of women reporting that they had not received a clinician's recommendation for endoscopy or home FOBT increased significantly. CONCLUSIONS: A lack of information, no clinician recommendation, misconceptions, and worry persist as barriers to colon cancer screening among this underscreened urban population. An increased focus on clinician recommendation and patient education about stool-based as well as endoscopic screening methods could lead to greater screening compliance. PMID- 22046853 TI - Early hospital discharge following breast cancer surgery in the West Indies: a Trinidad study. AB - PURPOSE: To examine the outcome of a policy of early hospital discharge (<24 hours) after breast cancer surgery in a Third World setting, where health care resources and support services are very limited. DESIGN: Prospective enrollment into a plan of early hospital discharge within 24 hours following breast surgery. Followup was conducted for wound infections; seroma formation; flap dehiscence; and readmission, if any. SUBJECTS: All patients over a 15-year period who underwent wide local excision or mastectomy and axillary clearance were enrolled. RESULTS: A total of 331 patients were entered into the study. Of these, 148 had modified radical mastectomy and 183 had wide local excision plus axillary dissection. Each patient had a drain placed and output was recorded. Follow-up revealed that there was no increase in the complication rates. CONCLUSION: Early hospital discharge following breast cancer surgery is a feasible option for most patients and can be safely implemented even in a resource-limited setting where cost containment is essential. PMID- 22046854 TI - T4b breast masses: a retrospective review of 12 cases presenting to a metropolitan tertiary care center. AB - INTRODUCTION: Due to increased awareness of breast cancer resulting in early detection, there is a decreased incidence nationwide of late-stage breast cancer, including that which presents with skin involvement (T4b). METHODS: A retrospective analysis of a 10-month period from August 2007 to May 2008 at Howard University Hospital (HUH), Washington, DC, revealed 12 patients diagnosed with T4b breast cancer and compared to similarly staged patients in the Surveillance, Epidemiology, and End Results (SEER) database. Finally, a logistic regression for the likelihood of T4b diagnosis was performed patients in the SEER database. RESULTS: HUH patients with T4b tumors were more likely than SEER patients to present with predictors of poor clinical outcome, including high grade histology (100% vs 59.4%, p = .04) and estrogen receptor- (75% vs 30.3%, p = .001) and progesterone receptor- negative (91.7% vs 43.9%, p = .001) status. Conversely, HUH patients were younger (57.8 y vs 66.3 y, p = .03) and had smaller tumors (11.1 cm vs 28.2 cm, p = .02) than SEER patients with similarly staged tumors. Older patients (OR, 2.36; 95% CI, 1.50-2.00; p < .001; 60-80 y), African American patients (OR, 1.63; 95% CI, 1.26-2.11; p < .001), and patients with high grade (OR, 5.51; 95% CI, 3.88-6.52; p < .001) tumors were more likely to be diagnosed with T4b tumors, whereas patients who lived in an area with increased median household income (OR, 0.99; 95% CI, 0.99-0.99; p = .001) were less likely to be diagnosed with a T4b lesion. CONCLUSION: While much research has focused on the socioeconomic causes for the development of T4b tumors, both patient and tumor biologic conditions cannot be eliminated as causative agents. PMID- 22046855 TI - A multimodal intervention to promote mammography and colorectal cancer screening in a safety-net practice. AB - BACKGROUND: There are limited data regarding interventions designed to improve cancer screening rates in safety-net practices with "real world" patients. OBJECTIVE: To examine the impact of a multimodal intervention on mammography and colorectal cancer (CRC) screening rates in a safety-net practice caring for underserved patients. METHODS: At an inner-city family medicine practice, all patients past due for mammography or CRC screening were assigned to receive or not receive a screening promotion intervention based on their medical record number. The 12-month intervention included outreach to patients (tailored letters, automated and personal phone calls) and point-of-care patient and clinician prompts. The trial was registered at clinicaltrials.gov, NCT00818857. RESULTS: We enrolled 469 participants aged 40 to 74 years, including 28% African Americans, 5% Latinos, 25% with Medicaid, and 10% without any form of insurance. Participants in the intervention group showed statistically significantly higher rates of cancer screening; rates were 41% vs 16.8% for mammography and 28.8% vs 10% for CRC screening. These findings were confirmed in multivariable analysis. Similar relative improvements in screening were seen across race, ethnicity, socioeconomic status, and insurance groups. DISCUSSION: A multimodal intervention shows promise for improving rates of mammography and colorectal cancer screening within a safety-net practice. Further study will identify the most cost-effective components of the intervention. PMID- 22046856 TI - Cause for concern: the state of affairs of adjuvant breast radiation among minority women with breast cancer. PMID- 22046857 TI - Mortality with fracture of the femur in African Americans in 2005-2006. PMID- 22046858 TI - The imperative for race-specific neutrophil count reference intervals in white cell count evaluation. PMID- 22046859 TI - [The European guidelines on residency training in anesthesiology, pain, and intensive care]. PMID- 22046860 TI - [Residency training in anesthesiology]. PMID- 22046861 TI - [An established anesthesia team-care model: over 12000 cases in a digestive endoscopy unit]. AB - BACKGROUND AND OBJECTIVE: The growing demand for digestive and other endoscopic procedures outside the operating room, both in terms of type of endoscopy and number of patients, requires reorganization of the anesthesiology department's workload. We describe 2 years of our hospital digestive endoscopy unit's experience with a now well-established care model involving both anesthesiologists and nurse anesthetists. MATERIAL AND METHODS: After previously reviewing the medical records of outpatients and conducting a telephone interview about state of health, nurse anesthetists administered a combination of propofol and remifentanil through a target-controlled infusion system under an anesthesiologist's direct supervision. RESULTS: The ratio of anesthesiologists to nurses ranged from 1:2 to 1:3 according to the complexity of the examination procedure. Over 12000 endoscopies (simple to advanced) in a total of 11853 patients were performed under anesthesia during the study period. Airway management maneuvers were required by 4.9% of the patients; 0.18% required bag ventilation for respiratory depression, and 0.084% required bolus doses of a vasopressor to treat hypotension or atropine to treat bradycardia. The procedure had to be halted early in 9 patients (0.07%). No patient required orotracheal intubation and none died. Nor were any complications related to sedation recorded. CONCLUSION: The results suggest that this care model can safely accommodate a large caseload in anesthesia at an optimum level of quality. PMID- 22046862 TI - [Ephedrine vs. phenylephrine by intravenous bolus and continuous infusion to prevent hypotension secondary to spinal anesthesia during cesarean section: a randomized comparative trial]. AB - OBJECTIVE: Subarachnoid spinal anesthesia for cesarean section is associated with a high incidence of hypotension, which can require the use of vasoconstrictors. The aim of this trial was to compare ephedrine to phenylephrine for the prevention of secondary hypotension and to assess the adverse effects on both mother and newborn. MATERIAL AND METHODS: Eighty patients undergoing elective or emergency cesarean section, in the absence of uterine activity or fetal risk, were randomized to receive prophylaxis with ephedrine or phenylephrine immediately after the spinal block. Patients in the ephedrine group received an intravenous bolus of 0.1 mg/kg plus continuous infusion at a rate of 0.5 mg/kg/h; patients in the phenylephrine group received an intravenous bolus of 1.5 microg/kg plus a continuous infusion at 1.5 microg/kg/min. Infusion was maintained until umbilical cord clamping. We recorded maternal blood pressure, heart rate, nausea and vomiting, dizziness, bradycardia, hypotension, hypertension, fetal Apgar index, and umbilical cord blood parameters (pH, PCO2, and HCO3). RESULTS: The overall incidence of hypotension was 11.2%, with no significant between-group differences (ephedrine group, 11.4%; phenylephrine group, 11.1%). The incidences of hypertension and bradycardia were higher in the phenylephrine group (27.8% and 2.3%, respectively) than in the ephedrine group (25% and 0%, respectively). Umbilical cord blood parameters and Apgar scores were similar. After suspension of continuous infusion, an episode of hypotension was detected in 22.5% of the patients (72.2% of these patients were in the phenylephrine group and 27.8% were in the ephedrine group). CONCLUSIONS: At the doses of ephedrine and phenylephrine administered in this trial, the ability of these drugs to prevent hypotension during cesarean section proved to be similar. Higher incidences of adverse events (hypertension and bradycardia) were observed in the phenylephrine group. No differences were observed in neonatal effects. PMID- 22046863 TI - [Estimating the angle of left lateral decubitus position during cesarean section: observational study of anesthesiologists' estimates and of midwives and nurses' level of understanding]. AB - OBJECTIVES: To determine the difference between the estimated and measured values of the left lateral decubitus (LLD) angle in the positioning of patients for scheduled cesarean section; to determine whether the accuracy of estimates differs between staff anesthesiologists and residents; and to assess the angle estimates of midwives and surgical nurses as well as their level of knowledge with respect to the utility of the LLD position. METHODS: This was a prospective, observational, double-blind study comparing staff anesthesiologists working in obstetrics to residents in their second, third, or fourth-year of training. We also presented a task and questions to midwives and surgical nurses who assisted during categories 3 and 4 cesarean sections (elective and scheduled procedures) according to the classification system of he National Institute of Clinical Excellence. The anesthesiologist was asked to place the patient in LLD position after onset of anesthesia and to estimate the LLD angle. A second anesthesiologist measured the angle. The midwives and nurses were asked to place a vacant surgical table at approximately 15 degrees; the angle was then measured. Patient variables (weight, height, anesthetic technique) and staff variables (position, understanding of the purpose of the maneuver, estimated DLL angle, and measured angle) were recorded. RESULTS: Of 55 women who underwent cesarean sections (98.18% under regional anesthesia), 25 were assessed by staff anesthesiologists and 30 by residents. A total of 14 midwives and 10 surgical nurses participated in the surgical table positioning task and answered questions. The mean (SD) DLL angle estimate of the anesthesiologists was 12.4 degrees (3.4 degrees); the mean measured angle was 7.8 degrees (3.1 degrees). The estimates of staff anesthesiologists were significantly more accurate (P < .001). All the midwives understood the reason for using the DLL position in cesarean section, while only 1 nurse (10%) did (P < .05). CONCLUSION: The DLL position angle is overestimated by resident anesthesiologists and midwives. It seems that the use and understanding of DLL positioning could be improved. PMID- 22046864 TI - [Anesthetic conserving device (AnaConDa) used after cardiac surgery: experience in a postoperative recovery unit]. AB - OBJECTIVE: To assess the safety and efficacy of using the Anesthetic Conserving Device (AnaConDa) when maintaining sedation after cardiac surgery. MATERIAL AND METHODS: Descriptive study of 46 consecutive patients in the postoperative recovery unit after cardiac surgery between January and April 2009. The patients were under sevoflurane sedation administered with the AnaConDa placed in the inhalation tube. No exclusion criteria were established before enrollment. The sevoflurane dose was set using the manufacturer's normogram and was later adjusted to give an end-tidal concentration of sevoflurane between 0.5% and 0.7% on the basis of data from a gas analyzer. Remifentanil was administered to all patients; a fast-track extubation protocol was used. The only criterion for excluding a patient's data from analysis was prolonged sedation (> 5 hours). RESULTS: The mean (SD) time patients were under sedation with the AnaConDa in place was 2588 (12.32) minutes. The end-tidal concentration of sevoflurane never exceeded 1%. Scores on the Richmond agitation-sedation scale were -5 at 60 minutes in all cases; there was some score variability at 120 minutes. Deeper sedation was desired for the first 60 minutes to avoid awakening related to rewarming. The mean time until awakening was 6.17 minutes (range, 1-30 minutes). The mean time until extubation was 43 (6.69) minutes. The most common adverse effect was arterial hypotension (12 cases). Hypotension was related to bleeding in 3 patients and to low cardiac output in 4 patients. CONCLUSION: Administering sevoflurane through the AnaConDa can be a safe, valid, and reliable method for sedating patients after cardiac surgery. With this device, it is possible to monitor the concentration administered. PMID- 22046865 TI - [Epiduroscopy]. AB - Epiduroscopy is a minimally invasive diagnostic and therapeutic technique used in patients with chronic low back pain with or without radiculopathy. Epiduroscopic procedures are particularly indicated in cases of failed spinal surgery. This review discusses the indications, contraindications, and complications of the technique, describing in detail the sacral (caudal) and interlaminar approaches and noting their advantages and disadvantages. Practical recommendations are made, along with an attempt to assess future prospects for epiduroscopy. PMID- 22046866 TI - [Neurologic complications of central neuraxial blocks]. AB - Central neuraxial blocks, which are associated with a low incidence of complications, are safe. When complications do occur, however, the resulting morbidity and mortality is considerable. The reported incidence of complications in all series is under 4 per 10000 patients, but given the absence of formal registries and notification procedures, which have legal implications, the real rate of occurrence of these rare events is uncertain. We searched the literature through PubMed and the Cochrane Plus Library for a 5-year period, using the search terms epidural anesthesia AND safety, spinal anesthesia AND safety, complications AND epidural anesthesia, complications AND spinal anesthesia, neurologic complications AND epidural anesthesia, and neurologic complications AND spinal anesthesia. Neuraxial injury after a central blockade may be the result of anatomical and/or physiological lesions affecting the spinal cord, spinal nerves, nerve roots, or blood supply. The pathophysiology of neuraxial injury may be related to mechanical, ischemic, or neurotoxic damage or any combination. When a complication occurs, factors related to the technique will have interacted with pre-existing patient-related conditions. Various scientific societies have published guidelines for managing the complications of regional anesthesia. Recently published clinical practice guidelines recommend ultrasound imaging as a useful tool in performing a central neuraxial block. PMID- 22046867 TI - [Reflections on residency training under the current recommendations of the European Union of Medical specialists and the European Board of Anaesthesia (UEMS/EBA guidelines)]. AB - The recent publication of guidelines for postgraduate training in anesthesiology, pain, and intensive care issued by the European Board of Anaesthesia (EBA) and the European Union of Medical Specialists (UEMS) (http://www.sedar.es/revistasedar/uems.pdf) specifies directions we must take with our residents. The training section of the Sociedad Espanola de Anestesiologia y Reanimacion (SEDAR) has decided to make the guidelines available on the association's website so that the UEMS/EBA proposals can be compared to the training program drafted by the Spanish national board for our specialty. Our aim is to identify points of convergence between the two proposals and to target gaps where improvements can be made so that Spanish residency training in this specialty is in harmony with the European framework. PMID- 22046868 TI - [Inhalation anesthesia during spontaneous ventilation in a patient with a tracheolaryngeal transplant requiring debridement of fibrous tissue obstructing the lumen]. AB - Graft stenosis from fibrous granulation tissue is not an uncommon problem in recipients of a transplanted trachea and larynx. We describe the case of a man with a transplanted trachea who was seen for respiratory difficulty and stridor secondary to stenosis. Examination through a rigid bronchoscope and surgical debridement were both performed under anesthesia with sevoflurane alone while the man breathed spontaneously. The outcome of treatment with sequential debridements of fibrotic tissue and autologous stem cell injection was satisfactory and the patient was discharged. PMID- 22046869 TI - [Treatment of a female patient with sickle-cell anemia during cardiac surgery with cardiopulmonary bypass]. AB - A 17-year-old girl with drepanocytic (sickle-cell) anemia who was being treated with hydroxyurea and periodic blood transfusions through a Hickman-type catheter was admitted for periodic episodes of fever. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus. Massive right atrial thrombosis with pulmonary embolism and bacterial endocarditis were detected by computed tomography. Surgery with a beating heart and cardiopulmonary bypass was undertaken. Drepanocytic anemia in individuals homozygous for hemoglobin S is a rare condition in Spain but we are beginning to see a few cases, in which management during anesthesia will be more complicated. High-risk surgery can be carried out in these patients without adverse events if the anesthesiologist is guided by a complete blood workup and takes precautions during and after surgery to control hydration, oxygenation, temperature, and the acid-base balance. PMID- 22046870 TI - [Comments on the article "Hypotensive resuscitation of the polytrauma patient with hemorrhagic shock"]. PMID- 22046871 TI - [Comments on the article "Perioperative anesthetic management of 300 morbidly obese patients undergoing laparoscopic bariatric surgery and a brief review of relevant pathophysiology"]. PMID- 22046872 TI - [Update on the use of opioids in acute, chronic, and breakthrough pain: an international symposium. Barcelona, February 2011]. PMID- 22046873 TI - [Unusual placement of a central venous catheter]. PMID- 22046874 TI - [Vertebral-jugular fistula after central venous catheterization]. PMID- 22046875 TI - [Forgotten HEART day]. PMID- 22046876 TI - [Intimomedial thickness of the vertebral arteries complex: a new useful parameter for the assessment of atheroclerotic process?]. AB - BACKGROUND/AIM: An integral part of Doppler ultrasound examination of cervical blood vessels is determination of intimomedial thicknes (IMT) of the common carotid. The aim of the study was to estimate the relations between IMT of the common carotid and vertebral arteries in order to determine if the value of IMT obtained on the vertebral artery could be applied in clinical practice. METHODS: We measured IMT in a randomized, prospective and cross-sectional study, performed on 50 persons both sexes (29 men and 21 women), at the age from 18 to 79 years (mean age 52.4 +/- 17.63 years). All the persons were healthy, what was confirmed with clinical examination and laboratory analyses. Measurements were perfomed from January 2006 until September 2008. Intimomedial thickness was recorded by two dimensional ultrasonography in B-mode on both common carotid arteries: one value was obtained as average of three successeful measurements (measurements were perform on different places). We measured IMT on the first segment of both vertebral arteries, 1.5 cm proximal from the connection of the first and second segments (we got results of the measurement of IMT on the vertebral arteries in the same way: mean value from the three records). RESULTS: The measured value of IMT on the common carotid arteries (IMT = 0.782 +/- 0.248 mm), obtained from 50 healthy persons, was higher than that measured on the vertabral artery on the first segment (IMT = 0.585 +/- 0.134 mm). The values of IMT after measurement on two different places were statistically highly different (t = 7.03, SD = 0.028, p < 0.01). Coefficient of variability of IMT values in carotid circulation (CV = 34.4%) was higher than that in vertebral circulation (22.9%). Values of IMT on vertebral arteries were in statistically significant correlation with those in carotid circulation (r = 0.24 and t- = 2.48; p < 0.02). There were no statistically significant difference between IMT measurement on the right and the left side so they were analysed as the same set. CONCLUSION: Values of IMT on the vertebral arteries are one more undependent parameter of Doppler-sonographic examination of cervical vessels, which significantly correlates with IMT values on common carotid artery. Variability of this parameter is lower, and absolute values lower than the same in the common carotid artery. Therefore, this parameter is probably not so sensitive. On the other hand, lower variability of IMT values on the vertebral artery might be of higher specificity for prediction of atherosclerotic progress by the increased values of this parameter than based on IMT values obtained on the common carotid arteries. PMID- 22046877 TI - Ultrasound measurement of visceral fat in patients with primary biliary cirrhosis. AB - BACKGROUND/AIM: Primary biliary cirrhosis (PBC) is a progressive, chronic liver disease with elevated serum lipids, but it is unclear whether hyperlipidemia in PBC patients is associated with atherosclerosis. Metabolic syndrome promotes development of atherosclerotic cardiovascular disease related to abdominal type obesity and insulin resistance. The aim of our study was to assess abdominal adiposity in patients with PBC. METHODS: The study included 40 patients with PBC and 50 healthy controls. Age, sex and anthropometric measurements (weight, height, body mass index and waist circumference) were registered for all patients and controls. We used ultrasonography to measure subcutaneous (SF) and visceral fat (VF) diameter, subcutaneous area (SA) and visceral area (VA), as well as perirenal fat diameter (PF). RESULTS: Values of SF, VF and PF thicknesses in PBC patients were 19.23 +/- 5.85 mm, 10.92 +/- 3.63 mm, and 7.03 +/- 1.82 mm, respectively. In controls these measurements were 22.73 +/- 6.70 mm, 16.84 +/ 5.51 mm and 10.50 +/- 2.70 mm respectively. In PBC patients SA and VA were calculated to 983.64 +/- 322.68 mm2 and 403.64 +/- 166.97 mm2 and in controls 1124.89 +/- 366.01 mm2 and 720.57 +/- 272.50 mm2 respectively. Significant difference was found for VF, VA and RF values. CONCLUSIONS: Considering that the amount of visceral fat plays an important role in development of metabolic syndrome and cardiovascular diseases, we concluded that the lower amount of visceral fat in PBC patients could be related to lower incidence of cardiovascular events, despite hyperlipidemia. PMID- 22046878 TI - [Endoscopic mucosal resection of colorectal tumors--our first experience]. AB - BACKGROUND/AIM: Endoscopic mucosal resection (EMR) or mucosectomy is an interventional procedure for minimal invasive endoscopic removal of benign and malignant digestive tract tumors. Mucosectomy removes flat and sessile neoplasms, early colorectal cancer (CRC) confined to mucosa or submucosa and lateral spreading tumors. The aim of the study was to show our first experience in application of this procedure in everyday practice in regarding completeness and efficacy of the procedure, complication rate and incidence of recurrent adenomas. METHODS: In the prospective study 51 colorectal adenomas were removed in 44 patients by EMR. RESULTS: Single mucosectomy was done in 43 patients, while multiple (8) in one patient. Complete resection was obtained in all procedures. In 36 (68.62%) procedures "en block" resection was done, but in 15 (31.37%) procedures "piece meal" resection was performed. Synchronous colorectal tumors (benign or malignant) were detected in 20 (45.45%) patients. Moderate dysplasia was found in 30 (58.82%) adenomas, but high grade dysplasia in 9 (17.64%) of adenomas. Intramucosal CRC was detected in 11.77% of adenomas. A total of 37 (72.54%) advanced adenomas were removed. There were 3 (5.88%) of recurrent adenomas, 6-30 months after the EMR. Only one (2.2%) case of post procedure bleeding was observed. CONCLUSION: EMR is a safe and efficious method for removal of flat, sessile adenomas, as well as early CRC. EMR is a routine endoscopic procedure in everyday practice of interventional endoscopist. PMID- 22046879 TI - [Influence of hemoglobin level and dose of administered recombinant human beta erythropoietin on survival of hemodialysis patients]. AB - BACKGROUND/AIM: In patients with end-stage renal disease, treatment with erythropoietin lowers cardiovascular morbidity, improves quality of life and patient survival. The aim of this study was to determine the difference in survival of hemodialysis patients treated with recombinant human beta erythropoietin and patients without this treatment, and to determine the influence of hemoglobin level and erythropoietin dose on the survival of these patients. METHOD: The study included 291 patients undergoing maintenance hemodialysis, 122 were on erythropoietin therapy, 169 patients formed control group. The study was performed at the Clinic for Nephrology and Clinical Immunology, Clinical Center of Vojvodina, during a 69-month period. We analyzed basic demographic parameters, dialysis duration, underlying disease, comorbidities, death causes, blood-work parameters and erythropoietin dosage. Descriptive statistics, Anova, Manova, discriminant function analysis, Cox regressional model and Kaplan Meier survival curves were used as statistical methods. RESULTS: Average age and dialysis duration in the experimental group were 47.88 +/- 13.32 years, and 45.76 +/- 46.73 months, respectively and in the control group 58.73 +/- 12.67 years and 62.80 +/- 55.23 months, respectively. Average level of hemoglobin and hematocrit in the group in which erythropoietin had been administered was 11.40 +/- 8.39 g/dL and 0.35 +/- 0.04/L, while the control group these values were 8.52 +/- 7.73 g/dL and 0.26 +/- 0.04/L, respectively. Average monthly dosage of erythropoietin was 21 587 +/- 10 183.36 IJ/month. Significant difference in survival was determined (p < 0.05) between the stated patient groups. A significant difference (p < 0.05) was found in survival of the patients in which erythropoietin was administered regarding hemoglobin level (< 100 g/L/100-110 g/L/110-120 g/L/ > 120 g/L), as well as in regard of erythropoietin dose applied (< 20 000 IJ/20 000-40 000 IJ/ > 40 000 IJ/month). CONCLUSION: Best survival was noted in patients with hemoglobin > 120 g/L and erythropoietin dose < 20 000 IJ/month. PMID- 22046880 TI - Influence of glucoregulation quality on C-reactive protein, interleukin-6 and tumor necrosis factor-alpha level in patients with diabetes type 1. AB - BACKGROUND/AIM: Results of studies which have proved an increased inflammatory activity in diabetes type 1, have been published over recent years. One of possible mechanisms that are used to explain chronic inflammation in diabetes is the state of hyperglycemia leading to the enhanced synthesis of glycosylation end products (AGEs) which activate macrophages, increase the oxidative stress and affect the synthesis of interleukins (IL-1, IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). The aim of the study was to determine the inflammatory markers (CRP, IL-6, TNF-alpha) in patients with diabetes type 1 and to establish their correlation with glucoregulation parameters and other cardiovascular risk factors as well as to compare them with the healthy controls. METHODS: The study included 76 patients with diabetes type 1 and 30 healthy controls. We determined values of inflammatory markers (CRP, IL-6, TNF-alpha) and glucoregulation parameters (fasting glucose HbA(1c)). RESULTS: The values of CRP (p = 0.014), IL-6 (p = 0.020) and TNF-alpha (p = 0.037) were statistically significantly higher in the diabetic patients than in the healthy controls. There was a positive correlation between CRP with postprandial glycemia (p = 0.004); the multivariate regression analysis revealed a statistically significant correlation between CRP and age (p = 0.001), smoking (p = 0.055), fasting glucose (p = 0.021) and triglycerides (p = 0.048) as well as between IL-6 and LDL cholesterol (p = 0.009). No statistically significant correlations were found between glycosilated hemoglobin (HbA(1c)) and the inflammatory markers (CRP, IL-6 and TNF-alpha). CONCLUSION: The patients with type 1 diabetes were found to have a low level of inflammatory activity manifested by the increased values of CRP, IL-6 and TNF-alpha. PMID- 22046881 TI - Bone bruise of the knee associated with the lesions of anterior cruciate ligament and menisci on magnetic resonance imaging. AB - BACKGROUND/AIM: Bone bruise is a common finding in acutely injured knee examined by magnetic resonance (MR). The aim of the study was to determine the association of bone bruise frequency with postinjury lesions of anterior cruciate ligament (ACL) and menisci. Bone bruise involves posttraumatic bone marrow change with hemorrhages, edema and microtrabecular fractures without disruption of adjacent cortices or articular cartilage. MR imaging is a method of choice for detecting bone bruises which can not be seen on conventional radiographic techniques. METHODS: A representative review of 120 MR examinations for the acute knee trauma was conducted. All the patients were examined within one month of trauma. All MR examinations were performed by using a 0.3T MR unit. RESULTS: Posttraumatic bone bruise was seen in 39 (32.5%) patients out of 120. Three patients had fracture of the cortex, so-called "occult" fracture (not seen on plain radiography). We analyzed only bone bruises without these fractures of the cortex. Bone bruise was associated with the lesion of ACL in 27 (69%) patients. In 28 (72%) patients bone bruise was in combination with the lesion of menisci. Only two patients with bone bruise had neither ACL nor menisci lesions. There were 78 patients without bone bruise but 33 (43%) of them had lesions of ACL and 49 (63%) had lesions of menisci. CONCLUSION: Bone bruise is best seen in STIR (Short TI Inversion Recovery) images and is very often found in acute knee trauma. Very often it is associated with posttraumatic lesions of ACL and menisci, so attention must be paid to this when bone bruise is seen. The difference in frequency of internal structures of the knee lesions in patients with bone bruise is highly statistically significant as compared to patients with no bone bruise. PMID- 22046882 TI - Possibilities of nontoxic autonomous thyroid nodules treatment by percutaneous ethanol injection. AB - BACKGROUND/AIM: According to the current principles, autonomous functional thyroid nodules are treated by surgery or by radioiodin therapy. Ultrasound guided percutaneous ethanol injection into solid tumors of the soft tissues was a starting point in attempts to treat the thyroid nodules by the same method. The aim of the study was to assess the efficiency of percutaneous injection in treating solitary, nontoxic, autonomous thyroid nodules of up to 15 mL volume. METHODS: In 25 patients with solitary nontoxic autonomous thyroid nodules diagnosed by tehnetium-99m scanning as an intensive area having a complete supremacy in the paranodal tissue, an ultrasound guided percutaneous ethanol injection was applied. The procedure was carried out repeatedly once a week until the reduction in nodule size to 50% of the initial size was achieved. RESULTS: An average size of the nodule before curing was 9.68 +/- 5.01 mL. An average quantity of the injected ethanol was 9.52 +/- 5.08 mL, ie 1.06 +/- 0.48 mL/mg of the tissue. The regression of the nodule size in the successfully (deltavol% u 57.09 +/- 13.75%, p < 0.001) and partly successfully cured (deltavol du = -48.45 +/- 14.35%, p < 0.05) was statistically significant compared to the size before the treatment. After ceasing ethanol injection, 18 months later, a further size regression (deltavol% = -79.20 +/- 9.89%) compared to the initial one (p < 0.001) was noticed. Soon, after the procedure was finished, a statistically significant concentration increase of Thyroid Stimulating Hormone (TSH) was noticed compared to the initial values (0.18 +/- 0.16 vs 0.34 +/- 0.31 mU/L, p < 0.01). According to the given criteria, in two female patients satisfactory results were not achieved, but, a year later, in one of them the nodule was not seen by repeated scintigram. The number and frequency of side effects were insignificant. CONCLUSION: Repeated percutaneous ethanol injections into nontoxic solitary autonomous thyroid nodules result in disappearing of authonomy. The regression of the nodule size of more than 50% compared to its initial volume, as well as the increase in concentration of TSH for more than 50% are the signs of a successful treatment. PMID- 22046883 TI - Arthroscopic partial medial meniscectomy. AB - BACKGROUND/AIM: Meniscal injuries are common in professional or recreational sports as well as in daily activities, If meniscal lesions lead to physical impairment they usually require surgical treatment. Arthroscopic treatment of meniscal injuries is one of the most often performed orthopedic operative procedures. METHODS: The study analyzed the results of arthroscopic partial medial meniscectomy in 213 patients in a 24-month period, from 2006, to 2008. RESULTS: In our series of arthroscopically treated medial meniscus tears we noted 78 (36.62%) vertical complete bucket handle lesions, 19 (8.92%) vertical incomplete lesions, 18 (8.45%) longitudinal tears, 35 (16.43%) oblique tears, 18 (8.45%) complex degenerative lesions, 17 (7.98%) radial lesions and 28 (13.14%) horisontal lesions. Mean preoperative International Knee Documentation Committee (IKDC) score was 49.81%, 1 month after the arthroscopic partial medial meniscectomy the mean IKDC score was 84.08%, and 6 months after mean IKDC score was 90.36%. Six months after the procedure 197 (92.49%) of patients had good or excellent subjective postoperative clinical outcomes, while 14 (6.57%) patients subjectively did not notice a significant improvement after the intervention, and 2 (0.93%) patients had no subjective improvement after the partial medial meniscectomy at all. CONCLUSION: Arthroscopic partial medial meniscetomy is minimally invasive diagnostic and therapeutic procedure and in well selected cases is a method of choice for treatment of medial meniscus injuries when repair techniques are not a viable option. It has small rate of complications, low morbidity and fast rehabilitation. PMID- 22046884 TI - Arterial hypertension in the elderly. PMID- 22046885 TI - [Nutrigenomics--the science of the 21st century]. PMID- 22046886 TI - Successful implantation of a permanent pacemaker through a persistent left superior vena cava by using a right subclavian approach. AB - INTRODUCTION: Persistent left superior vena cava, a rare congenital abnormality, can complicate placement of pacemaker leads through the subclavian vein. A left sided approach is usually preferable in such cases. CASE REPORT: We reported a case in which we began a single-chamber pacemaker implantation procedure via a right subclavian approach (because of scarring beneath the left clavicle) and then discovered intraoperatively that the patient had a persistent left superior vena cava. After a few attempts, we succeeded in placing the head of the electrode in the septum, near the top of the right ventricle, and the rest of the procedure was completed without complication. CONCLUSION: To our knowledge, this is the first reported case of pacemaker implantation, with passive electrode, through a persistent left superior vena cava via the right subclavian vein. This case demonstrates that such an approach, when necessary, can be used successfully. PMID- 22046887 TI - [Surgical treatment of unicentric plasma cell histological type Castleman's disease]. AB - INTRODUCTION: Castleman's disease or angiofollicular lymph hyperplasia is a rare disease with two identified clinical forms. Unicentric or localized form is characterized by isolated growth of lymph nodes, most often in mediastinum, and multicentric form is expressed as systemic disease with spread lymphadenopathy, organomegaly and presence of general symptoms of the disease. Histological types are hyalovascular, plasma-cell and transitive (mixed) cell. CASE REPORT: This case report shows a woman, 59 years old, with unicentric form of plasma-cell type of Castleman's disease. Unicentric form is usually shown as hyalovascular histological type, extremely rare as plasma-cell type, and transitive (mixed) cell type was never described in literature as localized clinical form. The disease was manifested with chest pain, loss of body weight, exhaustion and weakness of legs. Further diagnostic procedures found the presence of enlarged lymph nodes paratracheally right, in a close contact with vena cava superior. The disease was confirmed by histopathological analysis of bioptated mediastinal lymph node after mediastinoscopy. Surgical treatment included extirpation of enlarged lymph nodes. After the regular postoperative condition, a full therapy effect was confirmed. CONCLUSION: Unicentric form of Castleman's disease is expressed with enlarged lymph nodes on predilected places, usually in mediastinum. Surgical treatment is best method for the management of the disease and brings a full recovery of patient. PMID- 22046888 TI - [Simultaneous phacoemulsification, lens implantation and endothelial keratoplasty (triple procedure)]. AB - INTRODUCTION: Simultaneous Descemet stripping endothelial keratoplasty, phacoemulsification, and intraocular lens implantation are indicated in Fuchs' dystrophy with associated cataract. Compared to the standard method of the triple procedure which includes penetrating keratoplasty, this new method has the advantages of sutureless surgery, small limbal incision, faster recovery, less surface problems, less astigmatism, stronger tensile strength and more predictable calculation of the intraocular lens power. This is the first report of such a combination of procedures in our literature. CASE REPORT: A 76-year-old woman suffered from a gradual bilateral visual loss. The best corrected visual acuity was 20/60 (right eye) and finger counting at 1m (left eye). Corneal thickness was 590 microm and 603 microm, respectively. A marked cornea guttata and nuclear cataract were present in both eyes. Phacoemulsification, lens implantation, and Descemet stripping were done in the left eye. The posterior lamellar corneal graft, 8.0 mm in diameter and about 150 microm thick, was bent and inserted through the limbal incision. The air was injected into the anterior chamber to attach the graft to the recipient stroma. The cornea remained clear, and the transplant was attached during a two-year follow-up. Visual acuity was 20/40 after two months, and 20/25 after one year. CONCLUSION. The new technique proved itself as a good choice for the treatment of a mild Fuchs' dystrophy associated with cataract. PMID- 22046889 TI - [Sacral gigantocellular tumor treated with total sacrectomy and spinal-pelvic fixation]. AB - BACKGROUND: Total sacrectomy with spinal-pelvic fixation is considered to be a successful approach to the radical surgical treatment of extensive sacral tumors, however, technically very demanding, thus only rarely reported in the literature. We presented a patient with sacral gigantocellular tumor managed successfully using this method but with certain standard operative techniques improvements. CASE REPORT: A 30-year old patient with a pronounced painful syndrome and sphincter disorders was confirmed to have sacral gigantocellular tumor affecting a greater part of the sacrum. Tumor resection was performed in the first act out off retroperitoneal organs (colon and blood vessels), sacroiliac joints were open by the ventral side, the L5 discus removed, the S2-S5 roots cut off. In the second act, performed three weeks later, sacrectomy was completed by the reconstruction of pelvic ring and spinal-pelvic fixation. Then, the standard technique was modified to provide additional spinal fixation. The results of the operation (duration, blood loss, postoperative deficit) were quite comparable with, and in some aspects even better than the results published in the literature. CONCLUSION: Total sacrectomy with spinal-pelvic fixation can be a therapy of choice in patients with extensive sacral tumors requaring, however, the multidisciplinary approach and a considerable experience with instrumental spinal stabilization. PMID- 22046890 TI - [Brain tumors in patients primarly treated psychiatrically]. AB - INTRODUCTION: Psychiatric symptoms are not rare manifestations of brain tumors. Brain tumors presented by symptoms of raised intracranial pressure, focal neurological signs, or convulsions are usually first seen by the neurologist or less frequently by the neurosurgeon in routine diagnostic procedures. On the other hand, when psychiatric symptoms are the first manifestation in "neurologically silent" brain tumors, the patients are sent to the psychiatrist for the treatment of psychiatric symptoms and brain tumors are left misdiagnosed for a long period of time. CASE REPORT: We presented three patients with the diagnosed brain tumor where psychiatrist had been the first specialist to be consulted. In all three cases neurological examination was generally unremarkable with no focal signs or features of raised intracranial pressure. CT scan demonstrated right insular tumor in a female patient with obsessive-compulsive disorder (OCD); right parietal temporal tumor in a patient with delusions and depression and left frontal tumor in a patient with history of alcohol dependency. CONCLUSION: Psychiatric symptoms/disorders in patients with brain tumors are not specific enough and can have the same clinical presentation as the genuine psychiatric disorder. Therefore, we emphasize the consideration of neuroimaging in patients with abrupt beginning of psychiatric symptoms, in those with a change in mental status, or when headaches suddenly appear or in cases of treatment resistant psychiatric disorders regardless the lack of neurological symptoms. PMID- 22046891 TI - Time warp. Seeing people from the past. PMID- 22046892 TI - Knowing. It's a key component of a successful career. PMID- 22046893 TI - Just say no. With a drug test pending, an injured EMT wants no part of pain meds. PMID- 22046894 TI - The executive EMS officer. What values and competencies does an EMS executive need to succeed? PMID- 22046895 TI - Orthopedic assessment. Injured extremities need not just be left for the radiologist. PMID- 22046896 TI - Virtual care. How telemedicine is transforming the delivery of emergency medical services in the field. PMID- 22046897 TI - 6 easy steps to weathering the financial storm. By dismissing the "victim" mentality, you can create a blueprint to thrive. PMID- 22046898 TI - Strategizing for success. When it comes to managing a volunteer agency, evaluate operations much like you would patients to determine the best treatment option. PMID- 22046899 TI - When hypoglycemia attacks. The devastating effects of long-term diabetes and recurrent hypoglycemic events. PMID- 22046900 TI - Transition series: topics for the EMT. Part 5: Soft tissue injuries: crush injury and compartment syndrome. PMID- 22046901 TI - Safer new world. It's on everyone's minds in the ambulance business, and about to be move so. PMID- 22046902 TI - Anal medics: don't be a-freud. The traits that annoy others may make you a better caregiver. PMID- 22046903 TI - Blended learning: an ideal combination for dental practice. PMID- 22046904 TI - Contemporary adhesive bonding: bridging the gap between research and clinical practice. AB - The dawn of minimally invasive dentistry has led to the development of materials which rely on the use of effective adhesion to bond to remaining tooth tissue. Successful adhesive bonding is dependent upon appreciating the quality of the dental substrate, appropriate clinical handling of the material and patient, together with an appreciation of the chemistry of the adhesive. This paper outlines the current status of contemporary bonding, with particular emphasis on translating laboratory-based evidence into clinical practice. Using laboratory based evidence, the ability of a bond to achieve a seal to enamel appears to be the best predictor of clinical performance. CLINICAL RELEVANCE: This article discusses the issues raised when translating research data about adhesive bonding from the laboratory to clinical dental practice. PMID- 22046905 TI - Aesthetic smile evaluation--a non-invasive solution. AB - Enhancement of the aesthetic zone is a common reason for patients to seek dental care. This article describes a protocol for the examination, assessment and treatment planning for a patient seeking a solution to an aesthetic concern. The technique of undertaking an intra-oral'mock-up' using resin composite as a diagnostic approach can be particularly helpful when planning for future prosthodontic rehabilitation. The latter can allow the operator and patient to visualize crudely what is aesthetically and functionally possible, given the constraints imposed by that patient. The patient has ultimately managed in a minimally invasive manner. CLINICAL RELEVANCE: It can be very tempting for a dental operator to impose his/her concepts of the'artistic ideal' when planning for care in the smile zone. Such ideals are largely based on established universal aesthetic principles of tooth colour, size, shape, form, position, symmetry and proportion. However, beauty is a very subjective matter. It is essential for the operator to listen attentively to his/her patient's concerns. Meticulous patient examination and assessment are absolutely critical factors in attempting to attain a successful outcome. The use of reversible, chairside intra oral mock-up techniques can not only help with the transference of essential information to the dental technician when planning for restorative intervention in the smile zone, but can also allow the patient to gain an insight and indeed contribute his/her views to the possible restorative endpoint, respectively. PMID- 22046906 TI - Prosthodontic care for elderly patients. AB - For older patients, clinicians should consider maintaining teeth and using functionally-orientated treatment strategies as an alternative to removable prostheses. When the remaining dentition has a poor prognosis, key teeth should be preserved as overdenture abutments and a gradual transition to edentulousness planned. Where complete dentures are provided, these can be retained using dental implants to overcome many of the problems associated with conventional replacement dentures. CLINICAL RELEVANCE: The elderly population of today is better informed and more demanding of oral healthcare providers than previous generations. Clinicians should be aware of all the prosthodontic treatment options available for older patients. PMID- 22046907 TI - Primary cutaneous CD8-positive T-cell lymphoma: a case report of a rare and aggressive disease with oral presentation. AB - A case of a 66-year-old man, who was referred to the Oral Medicine service with persistent oral ulceration and widespread cutaneous rash is presented. Laboratory investigations confirmed a diagnosis of epitheliotropic, CD8-positive, cytotoxic, T-cell lymphoma. CLINICAL RELEVANCE: Oral ulceration represents a heterogeneous group of aetiologies: the patient with this more concerning pathology presented both to his general medical and dental practitioners. PMID- 22046908 TI - 'Simultaneous technique' and a hybrid Microseal/PacMac obturation. AB - In these endodontic case reports we present a root canal preparation protocol using the Mtwo Ni-Ti rotary files according to the 'simultaneous technique' which is a'crown-down' approach, where every instrument in the sequence is used to the full working length. A hybrid Microseal/PacMac obturation (consisting of three stages: master cone compaction, backfill with pre-plasticized guttapercha and vertical compaction) is proposed in order to: maintain the obturation length control associated with the Microseal system; use preheated gutta-percha to backfill the canal rapidly with the PacMac condensor; and to reduce potential voids in the obturation material with the final vertical compaction. CLINICAL RELEVANCE: The'simultaneous technique'followed by apical preparation using Mtwo apical files allows obturation using the proposed hybrid Microseal/Pacmac method, aiming to overcome some of the shortcomings of the Microseal and Pacmac obturation methods, such as length control difficulty and sealer pooling. PMID- 22046909 TI - Sickle cell disease, dentistry and conscious sedation. AB - The features of sickle cell disease (SCD) are described. Two case reports of patients treated in a Dental Institute are presented and the dental management of patients with SCD discussed. Since infection is one of the major risk factors for sickle cell crisis, the prevention of oral disease and infection is vital for this group of patients and there is no contra-indication to the delivery of dental treatment under local anaesthetic with inhalational sedation if required in the primary care setting. Since patients with sickle cell disease are particularly vulnerable to the effects of periods of hypoxia, which may produce significant morbidity, and because of the additional practical challenges in sedating this group of patients, intravenous sedation should be undertaken in a specialist unit. CLINICAL RELEVANCE: The increasing prevalence of sickle cell disease highlights the importance of dentists practising in multi-cultural communities having an understanding of this condition and its implications on their clinical practice. This will facilitate the safe management of patients with sickle cell disease. PMID- 22046910 TI - 'Shenanigans at the General Dental Council'. PMID- 22046911 TI - MHRA and CSD: here to help. PMID- 22046912 TI - Fluoride in the media: a review of newspaper articles from 1999 to 2009 (Dent Update 2011; 38:86-92). PMID- 22046913 TI - Oral cancer: comprehending the condition, causes, controversies, control and consequences. 9. Quality of life. PMID- 22046914 TI - Technique tips--a novel isolation technique for multiple severely broken down teeth requiring endodontic treatment. PMID- 22046915 TI - Physical signs for the general dental practitioner. Case 87. Adrenal insufficiency. PMID- 22046916 TI - Safe staffing levers should be mandatory. PMID- 22046917 TI - NMC and Unison clash over nurses' right to take industrial action. PMID- 22046918 TI - RCN lobbies House of Lords in bid to secure mandatory staff ratios. PMID- 22046919 TI - Head of Bahrain's nurses calls for backing of profession worldwide. PMID- 22046921 TI - Health visitors still under pressure despite their recent 'renaissance'. PMID- 22046920 TI - Lansley pledges to cut bureaucracy and drive up nursing care standards. PMID- 22046922 TI - Redundancy is personal. PMID- 22046923 TI - Packed and ready to go. AB - Timely discharge from hospital is a fundamental part of care that requires staff to be well trained, clear about their roles and open to innovative ideas. PMID- 22046924 TI - Burning issue. AB - Severe, persistent heartburn is a risk factor for a form of oesophageal cancer. Increasing awareness of this link among health professionals and the public could lead to earlier diagnosis and treatment. PMID- 22046925 TI - Improving health outcomes for people with learning disabilities. AB - Modern healthcare policy is driven by an emphasis on the philosophy of inclusion, yet in the past decade there has been increasing recognition that people with learning disabilities experience a range of difficulties when trying to access general healthcare services. The Disability Discrimination Acts of 1995 and 2005, and the Equality Act 2010, have driven service providers to find areas where 'reasonable adjustments' can be made to ensure improved health outcomes. This article considers the background context as well as exploring what reasonable adjustments mean in practice. PMID- 22046926 TI - Pain assessment tools for older people with cognitive impairment. AB - This article summarises and critiques various tools available for the assessment of pain in older people with cognitive impairment. Definitions of pain are numerous and are not always relevant to people with cognitive impairment because these individuals are often unable to describe or communicate their pain. This makes it difficult for healthcare professionals to assess the absence or presence of pain in these patients. The aim of this article is to establish which of the available pain assessment tools are most appropriate for use in older people with cognitive impairment. From a review of the literature, the authors conclude that pain assessment in older people with any degree of cognitive impairment is complex and there is no gold standard. PMID- 22046927 TI - Atrial fibrillation and primary stroke prevention. AB - Atrial fibrillation (AF) is a common cardiac arrhythmia that significantly increases the risk of ischaemic (embolic) stroke. The primary aim of this article is to help healthcare practitioners understand the link between AF and stroke and to assist them in assessing and managing high-risk patients. The association between a cardiac arrhythmia and a disabling cerebral event is not always understood fully. However, all healthcare professionals are in a position to identify patients with AF. PMID- 22046928 TI - Cancer cachexia. PMID- 22046929 TI - Divine community care. PMID- 22046930 TI - Meet with approval. PMID- 22046931 TI - Dummy run. PMID- 22046932 TI - Fluoride is an essential element of childhood oral health. PMID- 22046933 TI - Histologic, microbial testing to confirm dermatologic conditions. PMID- 22046935 TI - Improving adult immunization rates: overcoming barriers. PMID- 22046936 TI - Better integration of mental health care improves depression screening and treatment in primary care. PMID- 22046937 TI - Opioid antagonists for the treatment of alcohol dependence. PMID- 22046938 TI - Cognitive interventions for improving cognitive function. PMID- 22046939 TI - Shave and punch biopsy for skin lesions. AB - Shave and punch biopsies are essential procedures for physicians who manage skin conditions. These office-based procedures can diagnose questionable dermatologic lesions, including possible malignancies. Approaches include the superficial shave biopsy, saucerization excision, punch biopsy, and elliptical excision. A superficial shave biopsy can be used for raised lesions. A saucerization biopsy may be performed for flat or pigmented lesions. Punch biopsies yield full thickness samples and can be used for lesions that require dermal or subcutaneous tissue for diagnosis. Indications for biopsy of suspected melanoma remain controversial. Sufficient tissue may be obtained with the quicker, less costly saucerization biopsy or the more time-consuming, invasive elliptical excisional biopsy. PMID- 22046940 TI - Causes and evaluation of mildly elevated liver transaminase levels. AB - Mild elevations in levels of the liver enzymes alanine transaminase and aspartate transaminase are commonly discovered in asymptomatic patients in primary care. Evidence to guide the diagnostic workup is limited. If the history and physical examination do not suggest a cause, a stepwise evaluation should be initiated based on the prevalence of diseases that cause mild elevations in transaminase levels. The most common cause is nonalcoholic fatty liver disease, which can affect up to 30 percent of the population. Other common causes include alcoholic liver disease, medication-associated liver injury, viral hepatitis (hepatitis B and C), and hemochromatosis. Less common causes include alpha(1)-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease. Extrahepatic conditions (e.g., thyroid disorders, celiac disease, hemolysis, muscle disorders) can also cause elevated liver transaminase levels. Initial testing should include a fasting lipid profile; measurement of glucose, serum iron, and ferritin; total iron-binding capacity; and hepatitis B surface antigen and hepatitis C virus antibody testing. If test results are normal, a trial of lifestyle modification with observation or further testing for less common causes is appropriate. Additional testing may include ultrasonography; measurement of alpha(1) antitrypsin and ceruloplasmin; serum protein electrophoresis; and antinuclear antibody, smooth muscle antibody, and liver/kidney microsomal antibody type 1 testing. Referral for further evaluation and possible liver biopsy is recommended if transaminase levels remain elevated for six months or more. PMID- 22046941 TI - Elevated liver enzymes. PMID- 22046942 TI - Update on immunizations in adults. AB - Vaccine-preventable diseases contribute significantly to the morbidity and mortality of U.S. adults. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention updates its recommended adult immunization schedule annually. The most recent updates include the permissive but not routine use of the quadrivalent human papillomavirus vaccine to prevent genital warts in males; a single dose of herpes zoster vaccine for adults 60 years and older, regardless of their history; replacing a single dose of tetanus and diphtheria toxoids (Td) vaccine with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine in adults 19 years and older who have not previously received Tdap; expanding the indications for pneumococcal polyvalent-23 vaccine to include all adults with asthma and all smokers; annual seasonal influenza vaccination for all adults; and booster doses of meningococcal vaccine for adults with high-risk conditions. It is vital for family physicians to implement a systematic approach to adult immunization that is patient-, staff-, and physician focused. PMID- 22046943 TI - Diagnosis and management of osteomyelitis. AB - The incidence of chronic osteomyelitis is increasing because of the prevalence of predisposing conditions such as diabetes mellitus and peripheral vascular disease. The increased availability of sensitive imaging tests, such as magnetic resonance imaging and bone scintigraphy, has improved diagnostic accuracy and the ability to characterize the infection. Plain radiography is a useful initial investigation to identify alternative diagnoses and potential complications. Direct sampling of the wound for culture and antimicrobial sensitivity is essential to target treatment. The increased incidence of methicillin-resistant Staphylococcus aureus osteomyelitis complicates antibiotic selection. Surgical debridement is usually necessary in chronic cases. The recurrence rate remains high despite surgical intervention and long-term antibiotic therapy. Acute hematogenous osteomyelitis in children typically can be treated with a four-week course of antibiotics. In adults, the duration of antibiotic treatment for chronic osteomyelitis is typically several weeks longer. In both situations, however, empiric antibiotic coverage for S. aureus is indicated. PMID- 22046944 TI - Osteomyelitis: what you should know. PMID- 22046945 TI - Bubbles on the skin following renal transplant. PMID- 22046946 TI - Flaws in clinical reasoning: a common cause of diagnostic error. PMID- 22046949 TI - E-Z Gold Starter Kit Items Available. PMID- 22046950 TI - Vehicle head restraint positioning knowledge and behaviours in a sample of Irish drivers. AB - A correctly positioned vehicle head restraint (HR) can reduce whiplash injury risk in collisions, however, HRs are often sub-optimally positioned. The primary aim of this study was to investigate vehicle HR position and driver knowledge of correct HR positioning in an Irish population. Secondary aims were to investigate the associations with driver age, gender and vehicle age. Data collection involved HR measurement and a driver questionnaire (n = 110). Just 27% of drivers had optimal HR positioning, while 30% had poor or marginal positioning. Newer vehicles (<5 years old) had better positioned HR in the horizontal plane (p = 0.036), than older vehicles. Younger drivers (<30 years) were more likely to have poorer positioning of HR (p = 0.002), than the 30 years or over group. Females were more likely to have better vertical positioning of their HR (p = 0.003) than males. Driver knowledge of correct position was variable, and not associated with actual HR position, with 65% knowing the correct vertical positioning standard but only 27% identifying the correct horizontal position. Many drivers have inadequately positioned HR, which needs to be addressed by improved vehicle design and public education. PMID- 22046951 TI - Copper-catalyzed tyrosine nitration. AB - Tyrosine nitration, often observed during neurodegenerative disorders under nitrative stress, is usually considered to be induced chemically either by nitric oxide and oxygen forming nitrogen dioxide or by the decomposition of peroxynitrite. It can also be induced enzymatically by peroxidases or superoxide dismutases in the presence of both hydrogen peroxide and nitrite forming nitrogen dioxide and/or peroxynitrite. In this study, the role of cupric ions for catalyzing tyrosine nitration in the presence of hydrogen peroxide and nitrite, by a chemical mechanism rather similar to enzymatic pathways where nitrite is oxidized to form nitrogen dioxide, was investigated by development of a microreactor also capable of acting as an emitter for electrospray ionization mass spectrometry analysis. Indeed, cupric ions and peptide-cupric ion complexes are found to be excellent Fenton catalysts, even better than Fe(III) or heme, for the formation of (*)OH radicals and/or copper(II)-bound (*)OH radicals from hydrogen peroxide. These radicals are efficiently scavenged by nitrite anions to form (*)NO(2) and by tyrosine to form tyrosine radicals, leading to tyrosine nitration in polypeptides. We also show that cupric ions can catalyze tyrosine nitration from nitric oxide, oxygen, and hydrogen peroxide as the formation of tyrosine radicals is increased in the presence of diffusible and/or copper(II) bound hydroxyl radicals. This study shows that copper has a polyvalent role in the processes of tyrosine nitration. PMID- 22046953 TI - Asian-specific total knee system: 5-14 year follow-up study. AB - BACKGROUND: Knee size and body size differ in Asians compared with Caucasians. Nevertheless, many total knee arthroplasty (TKA) prostheses used worldwide are made for Western Caucasian subjects. As a result, an Asian's knee might not fit these prostheses. We studied the Flexible Nichidai Knee (FNK) system, a new model of TKA for Asian patients. The purpose of this report is to investigate the outcomes of this prosthesis retrospectively. METHODS: We investigated 1055 primary TKAs in 595 patients who underwent FNK for osteoarthritis (OA) in Japan and were followed for > 5 years. The knee score and function score were used for clinical evaluation. We examined the range of motion (ROM) preoperatively and at final follow-up and radiographic assessments. In addition, postoperative complications were investigated. A survivorship analysis was also conducted using two endpoints: revision for any reason and aseptic failure. RESULTS: 890 knees in 502 patients were available for study (follow-up rate of 96.0%). The mean follow up term was 8.3 years (range, 5.0-14.1 years). The knee and function score significantly improved from 41.3 to 90.3 and from 39.1 to 76.2 points, respectively (p < 0.001). The mean ROM in FNK posterior cruciate retaining (CR) type and FNK posterior-stabilized (PS) type ameliorated significantly from 107.8 degrees and 95.6 degrees to 110.7 degrees and 110.4 degrees , respectively (p < 0.01). Ten knees underwent revision surgery (infection in 3 cases, instability in 2, loosening in 2, and non-union of femoral supracondylar fracture, severe pain, and recurrent hemarthrosis in 1 each). The survivorship rate was 99.4% (95% CI, 99.0-99.8) at 5 years (n = 952 patients at risk) and 96.2% (95% CI, 91.9-100) at 12.5 years (n = 49 patients at risk). CONCLUSION: The FNK prosthesis for Asians achieved excellent mid- to long-term survivorship and clinical results. PMID- 22046952 TI - Immunobiotic lactic acid bacteria beneficially regulate immune response triggered by poly(I:C) in porcine intestinal epithelial cells. AB - This study analyzed the functional expression of TLR3 in various gastrointestinal tissues from adult swine and shows that TLR3 is expressed preferentially in intestinal epithelial cells (IEC), CD172a(+)CD11R1(high) and CD4(+) cells from ileal Peyer's patches. We characterized the inflammatory immune response triggered by TLR3 activation in a clonal porcine intestinal epitheliocyte cell line (PIE cells) and in PIE-immune cell co-cultures, and demonstrated that these systems are valuable tools to study in vitro the immune response triggered by TLR3 on IEC and the interaction between IEC and immune cells. In addition, we selected an immunobiotic lactic acid bacteria strain, Lactobacillus casei MEP221106, able to beneficially regulate the anti-viral immune response triggered by poly(I:C) stimulation in PIE cells. Moreover, we deepened our understanding of the possible mechanisms of immunobiotic action by demonstrating that L. casei MEP221106 modulates the interaction between IEC and immune cells during the generation of a TLR3-mediated immune response. PMID- 22046955 TI - Magnetic manipulation and optical imaging of an active plasmonic single-particle Fe-Au nanorod. AB - Superparamagnetic microbeads play an important role in a number of scientific and biotechnology applications including single-molecule force measurements, affinity separation, and in vivo and in vitro diagnostics. Magneto-optically active nanorods composed of single-crystalline Au and polycrystalline Fe segments were synthesized with diameters of 60 or 295 nm using templated electrodeposition. The Fe section was magnetically soft and had a saturation magnetization of approximately 200 emu/g, resulting in a 10-fold increase in magnetization relative to that iron oxide nanoparticles. The strong plasmonic response of the Au segment of the rod in both the longitudinal and transverse directions made it possible to detect the orientation of a single rod in a polarized light microscope with nanometer resolution. These nanorods provide significantly improved physical properties over iron oxide superparamagnetic beads, making it possible to simultaneously manipulate and monitor the orientation of biomolecules with well-defined forces at the nanometer scale. PMID- 22046954 TI - Raster-scanned carbon ion therapy for malignant salivary gland tumors: acute toxicity and initial treatment response. AB - BACKGROUND AND PURPOSE: To investigate toxicity and efficacy in high-risk malignant salivary gland tumors (MSGT) of the head and neck. Local control in R2 resected adenoid cystic carcinoma was already improved with a combination of IMRT and carbon ion boost at only mild side-effects, hence this treatment was also offered to patients with MSGT and microscopic residual disease (R1) or perineural spread (Pn+). METHODS: From November 2009, all patients with MSGT treated with carbon ion therapy were evaluated. Acute side effects were scored according to CTCAE v.4.03. Tumor response was assessed according to RECIST where applicable. RESULTS: 103 patients were treated from 11/2009 to 03/2011, median follow-up is 6 months. 60 pts received treatment following R2 resections or as definitive radiation, 43 patients received adjuvant radiation for R1 and/or Pn+. 16 patients received carbon ion treatment for re-irradiation. Median total dose was 73.2 GyE (23.9 GyE carbon ions + 49,9 Gy IMRT) for primary treatment and 44.9 GyE carbon ions for re-irradiation. All treatments were completed as planned and generally well tolerated with no > CTC degrees III toxicity. Rates of CTC degrees III toxicity (mucositis and dysphagia) were 8.7% with side-effects almost completely resolved at first follow-up.47 patients showed good treatment responses (CR/PR) according to RECIST. CONCLUSION: Acute toxicity remains low in IMRT with carbon ion boost also in R1-resected patients and patients undergoing re-irradiation. R2 resected patients showed high rates of treatment response, though follow-up is too short to assess long-term disease control. PMID- 22046956 TI - Effects of the distributions of energy or charge transfer rates on spectral hole burning in pigment-protein complexes at low temperatures. AB - Effects of the distributions of excitation energy transfer (EET) rates (homogeneous line widths) on the nonphotochemical (resonant) spectral hole burning (SHB) processes in photosynthetic chlorophyll-protein complexes (reaction center [RC] and CP43 antenna of Photosystem II from spinach) are considered. It is demonstrated that inclusion of such a distribution results in somewhat more dispersive hole burning kinetics. More importantly, however, inclusion of the EET rate distributions strongly affects the dependence of the hole width on the fractional hole depth. Different types of line width distributions have been explored, including those resulting from Forster type EET between weakly interacting pigments as well as Gaussian ones, which may be a reasonable approximation for those resulting, for instance, from so-called extended Forster models. For Gaussian line width distributions, it is possible to determine the parameters of both line width and tunneling parameter distributions from SHB data without a priori knowledge of any of them. Concerning more realistic asymmetric distributions, we demonstrate, using the simple example of CP43 antenna, that one can use SHB modeling to estimate electrostatic couplings between pigments and support or exclude assignment of certain pigment(s) to a particular state. PMID- 22046957 TI - Congruent genetic structure in the lichen-forming fungus Lobaria pulmonaria and its green-algal photobiont. AB - The extent of codispersal of symbionts is one of the key factors shaping genetic structures of symbiotic organisms. Concordant patterns of genetic structure are expected in vertically transmitted symbioses, whereas horizontal transmission generally uncouples genetic structures unless the partners are coadapted. Here, we compared the genetic structures of mutualists, the lichen-forming fungus Lobaria pulmonaria and its primary green-algal photobiont, Dictyochloropsis reticulata. We performed analysis of molecular variance and variogram analysis to compare genetic structures between symbiosis partners. We simulated the expected number of multilocus-genotype recurrences to reveal whether the distribution of multilocus genotypes of either species was concordant with panmixia. Simulations and tests of linkage disequilibrium provided compelling evidence for the codispersal of mutualists. To test whether genotype associations between symbionts were consistent with randomness, as expected under horizontal transmission, we simulated the recurrence of fungal-algal multilocus genotype associations expected by chance. Our data showed nonrandom associations of fungal and algal genotypes. Either vertical transmission or horizontal transmission coupled with coadaptation between symbiont genotypes may have created these nonrandom associations. This study is among the first to show codispersal and highly congruent genetic structures in the partners of a lichen mutualism. PMID- 22046958 TI - A comprehensive analysis of genes encoding small secreted proteins identifies candidate effectors in Melampsora larici-populina (poplar leaf rust). AB - The obligate biotrophic rust fungus Melampsora larici-populina is the most devastating and widespread pathogen of poplars. Studies over recent years have identified various small secreted proteins (SSP) from plant biotrophic filamentous pathogens and have highlighted their role as effectors in host pathogen interactions. The recent analysis of the M. larici-populina genome sequence has revealed the presence of 1,184 SSP-encoding genes in this rust fungus. In the present study, the expression and evolutionary dynamics of these SSP were investigated to pinpoint the arsenal of putative effectors that could be involved in the interaction between the rust fungus and poplar. Similarity with effectors previously described in Melampsora spp., richness in cysteines, and organization in large families were extensively detailed and discussed. Positive selection analyses conducted over clusters of paralogous genes revealed fast evolving candidate effectors. Transcript profiling of selected M. laricipopulina SSP showed a timely coordinated expression during leaf infection, and the accumulation of four candidate effectors in distinct rust infection structures was demonstrated by immunolocalization. This integrated and multifaceted approach helps to prioritize candidate effector genes for functional studies. PMID- 22046959 TI - Sclerotinia sclerotiorum gamma-glutamyl transpeptidase (Ss-Ggt1) is required for regulating glutathione accumulation and development of sclerotia and compound appressoria. AB - Transcripts encoding Sclerotinia sclerotiorum gamma-glutamyl transpeptidase (Ss Ggt1) were found to accumulate specifically during sclerotium, apothecium, and compound appressorium development in S. sclerotiorum. To determine the requirement of this protein in these developmental processes, gene deletion mutants of Ss-ggt1 were generated and five independent homokaryotic DeltaSs-ggt1 mutants were characterized. All deletion mutants overproduced sclerotial initials that were arrested in further development or eventually produced sclerotia with aberrant rind layers. During incubation for carpogenic germination, these sclerotia decayed and failed to produce apothecia. Total glutathione accumulation was approximately 10-fold higher and H(2)O(2) hyperaccumulated in DeltaSs-ggt1 sclerotia compared with the wild type. Production of compound appressoria was also negatively affected. On host plants, these mutants exhibited a defect in infection efficiency and a delay in initial symptom development unless the host tissue was wounded prior to inoculation. These results suggest that Ss-Ggt1 is the primary enzyme involved in glutathione recycling during these key developmental stages of the S. sclerotiorum life cycle but Ss-Ggt1 is not required for host colonization and symptom development. The accumulation of oxidized glutathione is hypothesized to negatively impact these developmental processes by disrupting the dynamic redox environment associated with multicellular development. PMID- 22046960 TI - N-terminal motifs in some plant disease resistance proteins function in membrane attachment and contribute to disease resistance. AB - To investigate the role of N-terminal domains of plant disease resistance proteins in membrane targeting, the N termini of a number of Arabidopsis and flax disease resistance proteins were fused to green fluorescent protein (GFP) and the fusion proteins localized in planta using confocal microscopy. The N termini of the Arabidopsis RPP1-WsB and RPS5 resistance proteins and the PBS1 protein, which is required for RPS5 resistance, targeted GFP to the plasma membrane, and mutation of predicted myristoylation and potential palmitoylation sites resulted in a shift to nucleocytosolic localization. The N-terminal domain of the membrane attached Arabidopsis RPS2 resistance protein was targeted incompletely to the plasma membrane. In contrast, the N-terminal domains of the Arabidopsis RPP1-WsA and flax L6 and M resistance proteins, which carry predicted signal anchors, were targeted to the endomembrane system, RPP1-WsA to the endoplasmic reticulum and the Golgi apparatus, L6 to the Golgi apparatus, and M to the tonoplast. Full length L6 was also targeted to the Golgi apparatus. Site-directed mutagenesis of six nonconserved amino acid residues in the signal anchor domains of L6 and M was used to change the localization of the L6 N-terminal fusion protein to that of M and vice versa, showing that these residues control the targeting specificity of the signal anchor. Replacement of the signal anchor domain of L6 by that of M did not affect L6 protein accumulation or resistance against flax rust expressing AvrL567 but removal of the signal anchor domain reduced L6 protein accumulation and L6 resistance, suggesting that membrane attachment is required to stabilize the L6 protein. PMID- 22046961 TI - Efficacy and safety of budesonide/formoterol via a dry powder inhaler in Chinese patients with chronic obstructive pulmonary disease. AB - OBJECTIVE: To evaluate the efficacy and safety of budesonide (BUD)/formoterol (FORM) compared with BUD, both administered by way of a dry powder inhaler (Turbuhaler * ). * Turbuhaler is a registered trade name of AstraZeneca, Sodertalje, Sweden. METHODS: This was a 6-month, multicenter, randomized, parallel-group, double-blind, double-dummy design study (NCT 00421122). Patients were randomized to either BUD/FORM 160/4.5 MUg, two inhalations twice daily, or BUD 200 MUg, two inhalations twice daily. Improvement of lung function, daily symptoms, reliever use and health-related quality-of-life (St George's Respiratory Questionnaire [SGRQ] score) were compared between the two treatment groups. RESULTS: A total of 308 patients with moderate to very severe COPD from 12 centers in China were randomized to BUD/FORM (n = 156) or BUD (n = 152). The primary endpoint, 1-hour post-dose forced expiratory volume in 1 second (FEV1), in the BUD/FORM group improved by 0.18 L (from 0.83 L at baseline to 1.01 L) and this was significantly better (p < 0.001) than the small increase (0.03 L) observed in the BUD group after 24 weeks' treatment. Increases in pre-dose and 15 min post-dose FEV(1) together with 1-hour post-dose forced vital capacity were also significantly larger with BUD/FORM than BUD (p < 0.001 for all). Compared with BUD alone, BUD/FORM improved COPD total symptom scores (-1.04 +/- 0.16 vs. 0.55 +/- 0.17; p = 0.03), reduced reliever use (-0.85 +/- 0.16 puffs/day vs. 0.31 +/- 0.16 puffs/day; p = 0.012) and improved health-related quality-of-life (mean change of total SGRQ score -4.5 points (p = 0.0182). Overall, both treatments were well tolerated. CONCLUSIONS: In Chinese patients with moderate to very severe COPD, fixed combination treatment with BUD/FORM resulted in clinically meaningful improvements in lung function, health-related quality-of life, COPD symptoms and a reduction in reliever use, compared with BUD alone and both treatments were well tolerated. Treatment of BUD/FORM for milder patients with COPD and head to head comparison of Chinese and Caucasians in future studies will be helpful to expand upon the findings of the current clinical trial. PMID- 22046963 TI - Photorelease of primary aliphatic and aromatic amines by visible-light-induced electron transfer. AB - Visible-light-absorbing tris(bipyridyl)ruthenium(II) has been used to mediate electron transfer to N-methylpicolinium carbamates that undergo C-O bond fragmentation followed by spontaneous carbon dioxide release to give free amines. Release of several aliphatic and aromatic primary amines has been demonstrated under mild conditions using visible light. PMID- 22046962 TI - Self-assembling, protein-based intracellular bacterial organelles: emerging vehicles for encapsulating, targeting and delivering therapeutical cargoes. AB - Many bacterial species contain intracellular nano- and micro-compartments consisting of self-assembling proteins that form protein-only shells. These structures are built up by combinations of a reduced number of repeated elements, from 60 repeated copies of one unique structural element self-assembled in encapsulins of 24 nm to 10,000-20,000 copies of a few protein species assembled in a organelle of around 100-150 nm in cross-section. However, this apparent simplicity does not correspond to the structural and functional sophistication of some of these organelles. They package, by not yet definitely solved mechanisms, one or more enzymes involved in specific metabolic pathways, confining such reactions and sequestering or increasing the inner concentration of unstable, toxics or volatile intermediate metabolites. From a biotechnological point of view, we can use the self assembling properties of these particles for directing shell assembling and enzyme packaging, mimicking nature to design new applications in biotechnology. Upon appropriate engineering of the building blocks, they could act as a new family of self-assembled, protein-based vehicles in Nanomedicine to encapsulate, target and deliver therapeutic cargoes to specific cell types and/or tissues. This would provide a new, intriguing platform of microbial origin for drug delivery. PMID- 22046964 TI - Fever and associated clinical haematologic and blood biochemical changes in the goat and other animal species. AB - Summary Acute febrile diseases are characterized by specific and non-specific symptoms. The non-specific responses are presented under the headings: fever, inflammation and pain, experimental models for investigating febrile reactions, haematologic changes, blood biochemical changes, cardiovascular effects, changes in gastric function, and the effects of fever upon pharmacokinetics of drugs. It was the purpose of this review to describe present concepts of thermoregulation and fever, the associated reactions produced by bacterial pyrogens and the mechanisms of these reactions. The available data illustrate, that many questions have not yet been clearly answered. However, the entire field of research involving endogenous substances, such as interleukin-1, is now moving ahead with great speed. Furthermore, there is some evidence which suggests that fever and the associated lower plasma zinc and iron levels act together as a co-ordinated non-specific host defence mechanism. Since experimental fever has a distinct effect upon the pharmacokinetics of drugs, more attention should be given to this aspect. PMID- 22046966 TI - Ficus platyphylla promotes fertility in female Rattus norvegicus Wistar strain: a preliminary study. AB - BACKGROUND: Ficus platyphylla Delile (family-Moracea) commonly called gutta percha tree is a deciduous plant found in savannah areas. It grows widely in the Northern part of Nigeria, up to 60 ft. high and is known as 'gamji' by the Hausas. The seeds, bark and leaves have been used traditionally in combination to promote fertility. Scientifically, the plant has been shown to have analgesic, anti-inflammatory and CNS effects. The present study was to validate the use of this plant to promote fertility in female Rattus norvegicus Wistar strain using various fertility parameters. METHODS: Female Rattus norvegicus Wistar strain weighing between 150-180 g were randomly selected and divided into two major groups. Each group was subdivided into 5 treatment groups of 100, 200, 400 mg/kg BW of aqueous extract of F. platyphylla and a control group of 5 ml/kg of distilled water. A positive control of clomiphene citrate was used. Treatment of the first group was discontinued after 15 days prior to mating (pre-mating treatment group), while the other was treated continuously till delivery (continuous treatment group). At the 10th day, females were sacrificed and implantation sites were checked and embryos counted. Upon delivery, litter sizes were determined and the pups weighed and checked for deformities. Other reproductive indices were calculated. Data were analyzed by one-way analysis of variance and students T-test. Proportions were analysed by Chi square. Statistical evaluations were performed using STATS programs and Graphpad prism, and a difference was considered statistically significant at P < 0.05. RESULTS: There was a significant reduction in the percentage post implantation losses of both the pre-treatment and the continuous treatment groups when compared to their distil water controls. The litter size of the pre-treatment group was similar to the distil water group while at 400 mg/kg, the continuous treatment group showed an increase in the litter size similar to that of the clomiphene group. There were no observed external deformities in the pups. CONCLUSIONS: Administration of aqueous extract of F. platyphylla promotes fertility by reducing post implantation loss and by increasing litter size in female Rattus norvegicus Wistar strain. PMID- 22046967 TI - Risk of infections in bronchiectasis during disease-modifying treatment and biologics for rheumatic diseases. AB - BACKGROUND: Bronchiectasis is frequently associated (up to 30%) with chronic inflammatory rheumatic diseases and leads to lower respiratory tract infections. Data are lacking on the risk of lower respiratory tract infections in patients treated with biologic agents. METHODS: Monocenter, retrospective systematic study of all patients with a chronic inflammatory rheumatic disease and concomitant bronchiectasis, seen between 2000 and 2009. Univariate and multivariate analyses were performed to evidence predictive factors of the number of infectious respiratory events. RESULTS: 47 patients were included (mean age 64.1+/-9.1 years, 33 (70.2%) women), with a mean follow-up per patient of 4.3+/-3.1 years. Rheumatoid arthritis was the main rheumatic disease (90.1%). The mean number of infectious events was 0.8+/-1.0 event per patient-year. The factors predicting infections were the type of treatment (biologic vs. non biologic disease modifying treatments), with an odds ratio of 8.7 (95% confidence interval: 1.7 43.4) and sputum colonization by any bacteria (odds ratio 7.4, 2.0-26.8). In multivariate analysis, both factors were independently predictive of infections. CONCLUSION: Lower respiratory tract infectious events are frequent among patients receiving biologics for chronic inflammatory rheumatic disease associated with bronchiectasis. Biologic treatment and pre-existing sputum colonization are independent risk factors of infection occurrence. PMID- 22046968 TI - Prevention of diabetes complications in developing countries: time to intensify self-management education. AB - The IDF report has indicated that about 80% of four million diabetes-related deaths that occur every year comes from the developing world. The IDF report suggests the need to focus more on preventing diabetes complications in poor countries. Thus, considering the economic constraints in combating the explosion of diabetes complications in the developing regions of the world, it appears that exploring culturally adaptable educational intervention programmes for specific regions would be the appropriate strategy. We believe that diabetes-related deaths could be reduced in developing countries through intensified diabetes self management education. PMID- 22046969 TI - A rapid microbioassay for discovery of antagonistic bacteria for Phytophthora parasitica var. nicotianae. AB - A simple, rapid, small-scale microbioassay for infection of tobacco seedlings by Phytophthora parasitica var. nicotianae was developed here. This assay uses tobacco seedlings cultivated in petri dishes for a standardized method for quantitation of initial zoospore inocula and high-throughput screening of antagonistic bacteria. Zoospore inocula between 10(2) to 10(5) spores per petri dish were inoculated on 14-day-old tobacco seedlings for the susceptibility test. The optimum inocula was established to be ten thousand zoospores. One hundred and fifty pure culture bacteria with different pigments, growth rates, and morphologies were isolated from rhizosphere soil of tobacco and screened for protective ability against tobacco black shank. Fifteen bacteria presented high activity against P. parasitica on tobacco seedlings. They were identified by Biolog GEN III MicroPlate and distributed as Bacillus amyloliquefaciens, B. licheniformis, Paenibacillus pabuli, B. atrophaeus, B. subtilis, B. pumilus, and B. endophyticus, respectively. Four antagonists chosen randomly from the 15 bacteria all exhibited the same 100% protective activity in planta as that in the petri dishes. This microassay proved to be a rapid, reproducible, and efficient method for screening of potential biological agents or microorganisms and may be useful for studying mechanisms of infection and control of Phytophthora spp. under hydroponic conditions. PMID- 22046970 TI - Differential expression of CD300a/c on human TH1 and TH17 cells. AB - BACKGROUND: Human memory CD4+ T cells can be either CD300a/c+ or CD300a/c- and subsequent analyses showed that CD4+ effector memory T (T(EM)) cells are mostly CD300a/c+, whereas CD4+ central memory T (T(CM)) cells have similar frequencies of CD300a/c+ and CD300a/c- cells. RESULTS: Extensive phenotypical and functional characterization showed that in both T(CM) and T(EM) cells, the CD300a/c+ subset contained a higher number of TH1 (IFN-gamma producing) cells. Alternatively, TH17 (IL-17a producing) cells tend to be CD300a/c-, especially in the T(EM) subset. Further characterization of the IL-17a+ cells showed that cells that produce only this cytokine are mostly CD300a/c-, while cells that produce IL-17a in combination with other cytokines, especially IFN-gamma, are mostly CD300a/c+, indicating that the expression of this receptor is associated with cells that produce IFN-gamma. Co-ligation of the TCR and CD300a/c in CD4+ T cells inhibited Ca2+ mobilization evoked by TCR ligation alone and modulated IFN-gamma production on TH1 polarized cells. CONCLUSION: We conclude that the CD300a/c receptors are differentially expressed on human TH1 and TH17 cells and that their ligation is capable of modulating TCR mediated signals. PMID- 22046971 TI - Belinostat: clinical applications in solid tumors and lymphoma. AB - INTRODUCTION: Histone deacetylase (HDAC) inhibitors have recently emerged as a novel and active class of anticancer agents. Belinostat is one member of the class that has been tested as a single agent and in combination with other chemotherapies and biological agents in the treatment of solid tumors and lymphoma. AREAS COVERED: A literature search of pre-clinical and clinical studies of belinostat was performed. The data from these studies were analysed to summarise the progress of belinostat from Phase I to a current pivotal trial in peripheral T-cell lymphoma. The parallel development of appropriate biomarker analysis is also discussed. EXPERT OPINION: Belinostat has demonstrated significant clinical activity in T-cell lymphomas. Although its activity as a single agent in solid tumors has been less compelling, the emerging results from combination trials are promising. However, the basis for the activity of belinostat, like that of other HDAC inhibitors, remains to be truly defined and the identification of predictive and prognostic biomarkers of activity should be established to further progress the development of this compound. PMID- 22046972 TI - Identifying and explicating variation among friends with benefits relationships. AB - This two-study report identifies and validates a typology containing seven types of "friends with benefits relationships" (FWBRs). Study 1 asked heterosexual students to define the term FWBR and to describe their experience with the relationship type. Qualitative analysis of these data identified seven types of FWBRs (true friends, network opportunism, just sex, three types of transition in [successful, failed, and unintentional], and transition out). Study 2 quantitatively differentiates these relationship types in the amount of nonsexual interaction, strength of the friendship at the first sexual interaction, and history of romantic relationships with the FWBR partner (before the FWBR, after it, or both). Results from both studies clearly suggest that FWBRs represent a diverse set of relationship formulations where both the benefits (i.e., repeated sexual contact) and the friends (i.e., relationship between partners) vary widely. In many cases, FWBRs represent a desire for, or an attempt at, shifting the relationship from friends to a romantic partnership. Other implications are discussed, as are limitations and directions for future research. The diverse nature of FWBRs provides challenges for researchers that likely require multiple methods and theoretical frames. PMID- 22046973 TI - The use of pharmacotherapy in pregnancies with suspected diabetic fetopathy. AB - OBJECTIVE: To review the evidence supporting incorporation of sonographic fetal measurements in deciding whether or not to add insulin to diet therapy independent of maternal glucose measures for women who have gestational diabetes. METHODS: A literature search was conducted for studies incorporating sonographic estimates of fetal measures in the selection of treatment. Only randomized controlled trials were selected for review. RESULTS: Four studies meeting selection criteria were identified. Methods of randomization, sonographic measurements used to indicate the addition of insulin for treatment, and clinical endpoints differed somewhat from study to study. Most studies reported a decrease in large neonates among women whose insulin treatment was indicated by ultrasound. In each study the targeted glucose values for patients treated with insulin based on sonographic measurements were lower than for those treated exclusively with diet. CONCLUSIONS: Available evidence suggests a benefit in reducing the incidence of large birth weight babies to mothers who have gestational diabetes by utilizing designated sonographic parameters in the decision to add pharmacotherapy in addition to using glucose thresholds. To support these findings, studies are needed in which glycemic targets comparing groups whose insulin treatment is based on maternal glucose results with those based on ultrasound measurements are identical. PMID- 22046974 TI - Evaluation of biomarkers of oxidative stress and antioxidant capacity in the cord blood of preterm low birth weight neonates. AB - OBJECTIVE: The objective of the study is to investigate the association between oxidative stress markers and enzymatic / non-enzymatic antioxidants (marker of the resistance in body to oxidative damage) in the cord blood of preterm low birth weight (LBW) neonates. METHODS: Malondialdehyde (MDA), carbonyl proteins, total antioxidant capacity and Vitamin A, E and C levels in the cord blood were determined by spectrophotometry. RESULTS: Increased lipid peroxidation, protein oxidation with decreased values of vitamin A, E, C and total antioxidant capacity were observed in the preterm LBW newborns. Observations of negative correlation between MDA and protein carbonyl with antioxidants vitamin A, E and C and total antioxidant status points towards the existence of oxidative stress in the preterm LBW newborns. CONCLUSIONS: Poor fetal growth affects the development of antioxidant defenses of preterm LBW babies, predisposing them to higher oxidative stress, which in turn may partly account for increased morbidity and mortality in these infants. The presence of an association between oxidative stress biomarkers and enzymatic /non-enzymatic antioxidants in the cord blood of preterm LBW neonates suggest that increased oxidative stress may be the result of changes in the levels of certain enzymatic and non-enzymatic antioxidants due to the cause or the effect of oxidative damage occurring at the molecular level. PMID- 22046975 TI - Comment on: guidelines for the management of spontaneous preterm labor: identification of spontaneous preterm labor, diagnosis of preterm premature rupture of membranes and preventive tools for preterm birth. PMID- 22046976 TI - Predictive factors of perinatal mortality in transfused fetuses due to maternal alloimmunization: what really matters? AB - INTRODUCTION: Alloimmunization is the main cause of fetal anemia. There are not many consistent analyses associating antenatal parameters to perinatal mortality in transfused fetuses due to maternal alloimmunization. The study aimed to determine the prognostic variables related to perinatal death. MATERIAL AND METHODS: A cohort study analyzed 128 fetuses treated with intrauterine transfusion (IUT), until the early neonatal period. Perinatal mortality was associated with prognostic conditions related to prematurity, severity of fetal anemia and IUT procedure by univariated logistic regression. Multiple logistic regression was used to compute the odds ratio (OR) for adjusting the hemoglobin deficit at the last IUT, gestational age at birth, complications of IUT, antenatal corticosteroid and hydrops. RESULTS: Perinatal mortality rate found in this study was 18.1%. The hemoglobin deficit at the last IUT (OR: 1.26, 95% CI: 1.04-1.53), gestational age at birth (OR: 0.53, 95% CI: 0.38-0.74) and the presence of transfusional complications (OR: 5.43, 95% CI: 142-20.76) were significant in predicting fetal death. CONCLUSION: Perinatal mortality prediction in transfused fetuses is not associated only to severity of anemia, but also to the risks of IUT and prematurity. PMID- 22046977 TI - Maternal serum interleukin-6 levels predict impending funisitis in preterm premature rupture of membranes after completion of antibiotics. AB - OBJECTIVE: To determine if maternal serum interleukin-6 (IL-6) levels remain predictive of funisitis after completion of antibiotic administration in preterm premature rupture of membranes (PPROM). METHODS: A secondary analysis of a prospective cohort study. Daily blood samples obtained from PPROM subjects were analyzed for IL-6 by enzyme-linked immunosorbent assay. Subjects (N = 39) delivered >7 days post admission and were divided into those with and without funisitis. Data were analyzed using Mann-Whitney U test. RESULTS: Maternal serum IL-6 levels obtained 24-48 hours and 48-72 hours before delivery are elevated in PPROM subjects with funisitis compared to those without funisitis (6.3 vs. 2.7 pg/ml, P < 0.03; 6.1 vs. 1.7 pg/ml, P < 0.02). Receiver operator characteristic curve revealed an IL-6 level of 1.98 pg/ml had sensitivity of 86.7%, specificity of 46.7%, positive predictive value of 61.9% and negative predictive value of 77.8%. CONCLUSION: This data suggests that maternal serum IL-6 levels continue to be predictive of PPROM subjects destined to develop funisitis after completion of antibiotics. PMID- 22046978 TI - Maternal N-acetyl-cysteine (NAC) protects the rat fetal brain from inflammatory cytokine responses to lipopolysaccharide (LPS). AB - OBJECTIVE: Inflammatory cytokines, play a central role in the genesis of preterm parturition and fetal brain injury. Lipopolysaccharide (LPS) may activate cytokine pathways via induction of oxidative stress pathways. We hypothesized that enhanced maternal antioxidant activity may blunt fetal brain inflammatory responses to maternal LPS injection in pregnant rats. METHODS: Pregnant Sprague Dawley rats at 18 and 20 days gestation received intraperitoneal (ip) LPS injection and pre- and post-treatment with the antioxidant N-acetyl-cysteine (NAC) or saline. Six hours after the LPS injection, rats were sacrificed, interleukin (IL)-6 and IL-10 mRNA expression in the fetal brains was determined by real time polymerase chain reaction. RESULTS: Maternal ip LPS induced significant increase in fetal brain IL-6 mRNA expression at E18 (3.1 +/- 0.6 vs 1.0 +/- 0.10 AU) and E20 (29.01 + 13.06 vs 0.95 + 0.05 AU; p < 0.05) compared to Control, only at E20 maternal LPS induced increase in fetal brain IL-10 compared to control. NAC administered prior to and after LPS significantly reduced fetal brain IL-6 at E18 and E20 and IL-10 at E20. CONCLUSION: Maternal NAC can protect the fetal brain from inflammatory cytokine responses to maternal LPS injection. These results suggest that NAC may potentially protect fetus from inflammation associated brain injury and potential long term sequelae. PMID- 22046980 TI - Errata. PMID- 22046982 TI - We Did It Our Way. PMID- 22046979 TI - A review of the responses of two- and three-dimensional engineered tissues to electric fields. AB - The application of external biophysical signals is one approach to tissue engineering that is explored less often than more traditional additions of exogenous biochemical and chemical factors to direct cell and tissue outcomes. The study of bioelectromagnetism and the field of electrotherapeutics have evolved over the years, and we review biocompatible electric stimulation devices and their successful application to tissue growth. Specifically, information on capacitively coupled alternating current, inductively coupled alternating current, and direct current devices is described. Cell and tissue responses from the application of these devices, including two- and three-dimensional in vitro studies and in vivo studies, are reviewed with regard to cell proliferation, adhesion, differentiation, morphology, and migration and tissue function. The current understanding of cellular mechanisms related to electric stimulation is detailed. The advantages of electric stimulation are compared with those pf other techniques, and areas in which electric fields are used as an adjuvant therapy for healing and regeneration are discussed. PMID- 22046983 TI - Announcement of the 2009 Paffenbarger Student Research Fellowship Award. PMID- 22046984 TI - 2010 Ralph Phillips Student Research Award Request for Applications. PMID- 22046986 TI - 39(th) Annual Meeting of the Academy of Operative Dentistry: 24-26 February 2010, Fairmont Hotel, Chicago, IL. PMID- 22046985 TI - E-Z Gold Starter Kit Items Available. PMID- 22046987 TI - Psychological adaptation of Moroccan and Ecuadorean immigrant adolescents in Spain. AB - In adapting to the host society, immigrant adolescents may have problems negotiating the challenges of acculturation. The factors that promote and those that hamper psychological adaptation may not play the same role in all ethnic groups. Our study focuses on psychological adaptation of two main immigrant groups in Spain that differ in cultural distance to the host society and level of societal acceptance: adolescents of Moroccan and Ecuadorean origin. Our findings show, first, that mainstream cultural orientation is positively related to psychological adaptation, whereas perceived ethnic discrimination is negatively associated with adaptation. Second, the relationship between ethnic cultural orientation and psychological adaptation and between length of residence in Spain and adaptation is stronger for the Moroccan youth than for their Ecuadorean peers. Theoretical and practical implications of these results are discussed. This manuscript was prepared and written while the first author was affiliated to the University of Cordoba in Spain and financially supported by the Spanish Ministry of Science and Innovation within the framework of a National Program of Human Recourses' Mobility (I+D+I 2008-2011). Data collection was financially supported by the Spanish Ministry of Science and Technology (I+D BSO2003-09222). PMID- 22046988 TI - Languages on the screen: is film comprehension related to the viewers' fluency level and to the language in the subtitles? AB - This research aimed at studying the role of subtitling in film comprehension. It focused on the languages in which the subtitles are written and on the participants' fluency levels in the languages presented in the film. In a preliminary part of the study, the most salient visual and dialogue elements of a short sequence of an English film were extracted by the means of a free recall task after showing two versions of the film (first a silent, then a dubbed-into French version) to native French speakers. This visual and dialogue information was used in the setting of a questionnaire concerning the understanding of the film presented in the main part of the study, in which other French native speakers with beginner, intermediate, or advanced fluency levels in English were shown one of three versions of the film used in the preliminary part. Respectively, these versions had no subtitles or they included either English or French subtitles. The results indicate a global interaction between all three factors in this study: For the beginners, visual processing dropped from the version without subtitles to that with English subtitles, and even more so if French subtitles were provided, whereas the effect of film version on dialogue comprehension was the reverse. The advanced participants achieved higher comprehension for both types of information with the version without subtitles, and dialogue information processing was always better than visual information processing. The intermediate group similarly processed dialogues in a better way than visual information, but was not affected by film version. These results imply that, depending on the viewers' fluency levels, the language of subtitles can have different effects on movie information processing. PMID- 22046989 TI - Aspirations and wellbeing in Romanian and US undergraduates. AB - Updating cross-cultural research of the past decade on the relationship between life aspirations and wellbeing, we compared Romanian (N=69) and US (N=64) undergraduates on the contribution of the importance and likelihood of attaining intrinsic and extrinsic aspirations to psychological maladjustment and life satisfaction, and on the qualitative meaning they assign to financial success. Similarly to prior studies, we found that extrinsic and intrinsic aspirations tended to be either negatively or positively correlated with life satisfaction, respectively; however, wealth predicted life satisfaction for Romanian students. Unlike previous research, we found generally negative relationships between intrinsic aspirations and psychological maladjustment. Although there were no differences between Romanian and US undergraduates on extrinsic and intrinsic orientation, on the overall importance of attaining aspirations, or on specific extrinsic and intrinsic aspirations, Romanian students expressed weaker expectations of fulfilling intrinsic aspirations than did US students. Finally, the groups produced similar rankings of aspirations and assigned similar meaning to financial success. The results favored a social cognitive rather than a self determination model of psychological wellbeing in that expectations for attaining aspirations were more often predictive of life satisfaction than were their content. We interpret these findings and their convergence and departure from earlier research in terms of political economic, demographic, and cultural factors. We encourage future cross-cultural investigations of the social construction of aspirations, subsidiation of seemingly contradictory aspirations to each other, and cognitive and ecological mediation of the complex relationship of aspirations to psychological functioning. PMID- 22046990 TI - The effects of mortality salience on escalation of commitment. AB - Based on propositions derived from terror management theory (TMT), the current study proposes that people who are reminded of their mortality exhibit a higher degree of self-justification behavior to maintain their self-esteem. For this reason, they could be expected to stick with their previous decisions and invest an increasing amount of resources in those decisions, despite the fact that negative feedback has clearly indicated that they might be on a course toward failure (i.e., "escalation of commitment"). Our experiment showed that people who were reminded of their mortality were more likely to escalate their level of commitment by maintaining their current course of action. Two imaginary scenarios were tested. One of the scenarios involved deciding whether to send additional troops into the battlefield when previous attempts had failed; the other involved deciding whether to continue developing an anti-radar fighter plane when the enemy had already developed a device to detect it. The results supported our hypothesis that mortality salience increases the tendency to escalate one's level of commitment. PMID- 22046991 TI - Taiwanese adolescent cognitive autonomy and identity development: the relationship of situational and agential factors. AB - Taiwanese professionals have adopted information about adolescent psychosocial development from Western societies. However, scholars know little about whether they have properly applied the models to both rural and urban youth. The purpose of this study was to examine the development of cognitive autonomy and ego identity in Taiwanese adolescents from Taipei City and surrounding rural counties. We controlled for gender and examined both situational (residential location, family income, and school type) and agential factors (culture value affiliation, attachment, and resiliency) to determine the extent to which each predicted psychosocial developmental outcomes. Among all the factors in this study, resiliency had the most distinctive relationship with adolescent psychosocial development. Each factor successfully predicted specific aspects of psychosocial development for these youth. We conclude with a discussion of the utility of using Western models of development. PMID- 22046992 TI - Perceived discrimination, social connectedness, and other predictors of adjustment difficulties among Turkish international students. AB - This study examined the role of perceived discrimination, social connectedness, age, gender, years of study in the US, English language competency, and social contact patterns on adjustment difficulties among a sample of 229 Turkish international students studying in the United States. Findings indicated that students who reported higher levels of social connectedness, lower levels of perceived discrimination, more years of study in the US, and higher levels of English language competency reported lower levels of adjustment difficulties. Other results showed that (lack of) social connectedness and perceived discrimination were predictors of adjustment difficulties. In addition, results indicated that students who socialized with individuals from the US had lower levels of adjustment difficulties than did those who socialized with coculture members. Implications are discussed and suggestions for interventions are provided. PMID- 22046993 TI - The effects of functional group counseling on inspiring low-achieving students' self-worth and self-efficacy in Taiwan. AB - In this study, we investigated the effects of functional group counseling on inspiring low achievers' self-worth and self-efficacy in Taiwan. Forty-three 10th grade low-achieving students volunteered as the Experimental Group to join a 24 week intervention, which integrated and utilized functional group counseling; another 51 10th grade low-achieving students volunteered to be Comparison Group I. In addition, 43 10th grade moderate or high academic achieving students volunteered to be Comparison Group II. All participants completed the Vocational School Student Questionnaire at the beginning and end of this study to measure their self-worth and self-efficacy. In addition, six target students (two boys and four girls) with the lowest total scores on self-worth or self-efficacy in the pretest were selected from the Experimental Group to be interviewed at the end of the intervention and observed weekly. Analyses of variance, analyses of covariance, and paired t-tests assessed the similarity and differences among groups. The initial findings were as follows: Experimental group students had significantly higher scores on self-efficacy and self-worth than both Comparison Group I and Group II students and functional group counseling was shown to significantly affect the low-achieving students. Qualitative results from interviews and observations were used for triangulation and consolidation of quantitative results. Implications of the study included the recommended use of functional group counseling with low-achieving students. PMID- 22046994 TI - The effect of achievement goals on enjoyment, effort, satisfaction and performance. AB - This study examined the effect of achievement goals and achievement emotions on sport satisfaction, performance and effort among competitive athletes. Participants were 200 athletes. Structural equation modeling was used to test the indirect effect of mastery-approach goals on satisfaction with sport experience and performance, the direct effect of mastery-approach goals on enjoyment and effort, the direct effect of performance-approach and performance-avoidance goals on performance, and the direct effect of mastery-avoidance goals on effort. Results showed a positive direct effect of mastery-approach goals on enjoyment and an indirect effect, through enjoyment, on satisfaction, performance, and effort. We did not find support for the hypothesized effect of performance approach or performance-avoidance goals on performance. The applied implications of endorsing mastery-approach goals are discussed. PMID- 22046995 TI - Motivation and social contexts: a crossnational pilot study of achievement, power, and affiliation motives. AB - Previous research suggests that there is a relationship between social contexts (e.g., economic growth, engagement in wars) and motives within populations. In particular, high achievement motive is associated with subsequent economic growth, which in turn increases power motive. Increased national achievement and power motives have been argued to precede social changes that lead to decreased affiliation motives, and engagement in wars. The present study aimed to examine differences in achievement, power, and affiliation motives between 266 college students in China (a nation with sustained high economic growth) and 255 college students in the USA (a nation with previously strong but now slowing economic growth, and engaged in war). Analysis of personal strivings suggested that Chinese college students showed significantly higher levels of achievement motive than the American college students, but American college students showed significantly higher levels of affiliation motive than Chinese college students. Overall, males exhibited higher achievement motivation than females. No significant interaction effects were found for gender by location for any of the three motives. The findings are discussed in relation to previous research. PMID- 22046996 TI - Cultural differences in athlete attributions for success and failure: the sports pages revisited. AB - Self-serving biases in attribution, while found with relative consistency in research with Western samples, have rarely been found in Japanese samples typically recruited for research. However, research conducted with Japanese participants to date has tended to use forced-choice and/or reactive paradigms, with school or university students, focusing mainly on academic performance or arbitrary and/or researcher-selected tasks. This archival study explored whether self-serving attributional biases would be shown in the real-life attributions for sporting performance made by elite Olympic athletes from Japan and Australia. Attributions (N = 216) were extracted from the sports pages of Japanese and Australian newspapers and rated by Australian judges for locus and controllability. It was hypothesized that Australian, but not Japanese, athletes would show self-serving biases such that they attributed wins to causes more internal and controllable than the causes to which they attributed losses. Contrary to predictions, self-serving biases were shown to at least some extent by athletes of both nationalities. Both Australian and Japanese men attributed wins to causes more internal than those to which they attributed losses. Women, however, attributed wins and losses to causes that did not differ significantly in terms of locus. All athletes tended to attribute wins to causes that were more controllable than the causes to which losses were attributed. Results are inconsistent with a large body of research suggesting that Japanese do not show self-serving biases in attribution, and are discussed in the light of differences in methodology, context, and participants that may have contributed to these effects. PMID- 22046997 TI - Affective responses to movie posters: differences between adolescents and young adults. AB - Although the link between cognition and affect in the advertising context has been demonstrated in several studies, no research to date has considered adolescents' affective responses to movie posters and their attitudes to negative and positive images. A 2 (between subjects) * 4 (within subjects) mixed-factorial experiment design comprising two groups of subjects (80 adolescents and 80 young adults) and four advertising stimuli (two highly positive images and two highly negative images) was used to test the differences in the subjects' attitudes to advertising, positive and negative affect, and viewing intentions. Although the adolescents, compared to the young adults, did not appear to have significantly stronger attitudes to emotional advertisements (ads), they showed a similar level of intensity of affective response when exposed to negative and positive images. PMID- 22046998 TI - Gender and work-family conflict: testing the rational model and the gender role expectations model in the Spanish cultural context. AB - Gutek, Searle, and Klepa (1991) proposed two models to explain the gender differences in work-family conflict: the rational model and the gender role expectations model. Both models have mostly been tested on American and Canadian samples, and have obtained partial support. Given the cultural differences between North American countries and Spain, we should question whether the two models are equally applicable to Spanish society or whether one of them captures Spanish men and women's experience of work-family conflict better than the other. So, the aim of this study is to test which of the models better explains the gender differences in work-family conflict in the Spanish cultural context (or if, indeed, the two models apply equally well). Given the typical cultural dimensions of Spanish society, we expected to find greater support for the gender role expectations model than for the rational model. However, the results obtained in this study indicated that, while the rational model can explain the gender differences that were found, the gender role expectations model cannot capture Spanish people's work-family conflict experiences. The results are interpreted in terms of cultural dimensions characteristic of the Spanish context. PMID- 22046999 TI - Posttraumatic stress and worry as mediators and moderators between political stressors and emotional and behavioral disorders in Palestinian children. AB - This study was designed to assess whether the symptoms of posttraumatic stress mediate or moderate the relationship between political stressors and emotional and behavioral disorders in Palestinian children. It was hypothesized that (a) posttraumatic stress and worry mediate the effect of political stressors on behavioral and emotional disorders and (b) the relationship between political stressors and behavioral and emotional disorders should be attenuated for children with low levels of worry and posttraumatic stress and strengthened for children with high levels of worry and posttraumatic stress. The total sample was 1267 school age children of both sexes with a mean age of 11.97 years. Interviews were conducted with children at school. As hypothesized, the results indicated that posttraumatic stress and worry mediated and moderated the relationship between political stressors and emotional and behavioral disorders in children. Cognitive-behavioral therapy may be used to reduce the incidence of posttraumatic stress and decrease self-reported worry, somatic symptoms, general anxiety, and depression among children exposed to political trauma. Cognitive-behavioral treatment that exclusively targets excessive worry can lead to clinical change in the other interacting subsystems at the cognitive, physiological, affective and behavioral levels. PMID- 22047000 TI - Different brain mechanisms between stereotype activation and application: evidence from an ERP study. AB - Stereotyping involves two processes in which first, social stereotypes are activated (stereotype activation), and then, stereotypes are applied to given targets (stereotype application). Previous behavioral studies have suggested that these two processes are independent of each other and may have different mechanisms. As few psychophysiological studies have given an integrated account of these stages in stereotyping so far, this study utilized a trait categorization task in which event-related potentials (ERPs) were used to explore the brain mechanisms associated with the processes of stereotype activation and its application. The behavioral (reaction time) and electrophysiological data showed that stereotype activation and application were elicited respectively in an affective valence identification subtask and in a semantic content judgment subtask. The electrophysiological results indicated that the categorization processes involved in stereotype activation to quickly identify stereotypic and nonstereotypic information were quite different from those involved in the application. During the process of stereotype activation, a P2 and N2 effect was observed, indicating that stereotype activation might be facilitated by an early attentional bias. Also, a late positive potential (LPP) was elicited, suggesting that social expectancy violation might be involved. During the process of the stereotype application, electrophysiological data showed a P2 and P3 effect, indicating that stereotype application might be related to the rapid social knowledge identification in semantic representation and thus may be associated with an updating of existing stereotypic contents or a motivation to resolve the inconsistent information. This research strongly suggested that different mechanisms are involved in the stereotype activation and application processes. PMID- 22047001 TI - Subjective wellbeing and its relationship with academic achievement and multilinguality among Lebanese university students. AB - The study investigated three subjective wellbeing (SWB) components, namely positive affect (PA), negative affect (NA), and life satisfaction (LS), along with optimism and self-esteem and their association with academic achievement and multilinguality in a sample of 1401 Lebanese university students. As predicted, optimism and self-esteem correlated positively with LS and PA, and negatively with NA. Optimism, self-esteem and each of the SWB components jointly predicted academic achievement (GPA), with PA being an individually significant positive predictor. There were differences in the five key variables across language groups, specifically between Arabic-only speakers and some other groups: Compared Arabic-only speakers, bilingual speakers of Arabic and either English or French scored higher on self-esteem, PA and optimism, and lower on NA, while trilingual speakers of Arabic, English, and French scored higher on self-esteem, PA and LS. Language grouping was a significant predictor of the SWB components, optimism, and self-esteem even when controlling for GPA, socioeconomic status (SES), and religion. Lastly, the relevance of SES and religion for the prediction of SWB is discussed, and implications and future research questions are advanced. PMID- 22047002 TI - Coverage of Russian psychological contributions in American psychology textbooks. AB - Internationalizing psychology is an important component of current globalization trends. American textbooks on the history of psychology and introductory psychology were surveyed for the presence of historical and contemporary important Russian psychologists to assess the current status of Russian-American crossfertilization. Of a list of 97 important Russian psychologists, as determined by the editors of the Russian journal Methodology and History in Psychology, less than 22% are mentioned in the reviewed texts. The most common names were Pavlov, Luria, and Vygotsky. As the internet is arguably the single most important factor affecting the increase of international communication and dissemination of knowledge, we also searched for these 97 names on various websites, most notably Wikipedia and Google. Forty-one internet sites contained some amount of biographical information about Russian psychologists. On Wikipedia, 14 Russian psychologists had articles documenting biographical information. We also developed a rubric to determine the amount of information available on the internet for these psychologists and compared Wikipedia's mean score with various other websites. Wikipedia pages on average had a significantly higher score than the rest of the internet. Recommendations to improve Russian coverage in America are provided and include: (1) developing pages on Wikipedia and other virtual venues highlighting Russian contributions, (2) soliciting articles for US journals from Russian psychologists, and (3) incorporating Russian contributions in introductory and historical textbooks. We provide a partial bibliography of Russian contributions that can be used by authors of such textbooks. We would like to thank Dr Viktor Fedorovich Petrenko and Dr Igor Nikolaevich Karitsky from the journal Methodology and History of Psychology for supplying the names of the Russian psychologists. We would also like to express our appreciation to Robert Garcia for reviewing and editing an earlier version of this manuscript. PMID- 22047003 TI - Insulin analogues: how observational studies provide key insights into management of patients with type 2 diabetes mellitus. AB - OBJECTIVE: The aim of this commentary was to evaluate the current evidence regarding the use of synthetic insulin analogues in the 'real-world' clinic setting for the treatment of type 2 diabetes mellitus (T2DM). METHODS: Relevant publications were searched on PubMed MEDLINE, EMBASE, Cochrane Register of Controlled Trials Google Scholar, NLM Gateway, Science Direct, Web of Science and OVID for the period of January 2007 to June 2010. Articles were included if they (a) provided specific study results on the use of insulin analogues in T2DM and (b) gave sufficiently clear methodology details to establish treatment strategies, diagnosis and diagnostic criteria using an observational study (OS) design. RESULTS: Twenty one articles specifically addressing both type 2 diabetes management and the use of synthetic insulin analogues were identified. Results from recently published OS in patients with T2DM have shown, in the patient populations tested, the effective initiation, optimization and switch to use of insulin analogues in routine clinical settings (day-to-day common practice), with a good safety profile. CONCLUSIONS: OS can provide clinicians with additional insights into the management of T2DM patients in their practices. However, the selection and initiation of insulin analogue regimens should be tailored to the individual patient and be one that the physician is comfortable using. PMID- 22047004 TI - Sponge-to-lamellar transition in a double-tail cationic surfactant/protic ionic liquid system: structural and rheological analysis. AB - The self-assembly of didodecyldimethylammonium bromide (DDAB) in a protic ionic liquid, ethylammonium nitrate (EAN), in the high surfactant concentration regime is studied using five different experimental techniques. A thermoreversible first order sponge (L(3)) to lamellar (L(alpha)) transition occurring at [DDAB] > 80 wt % was identified by (1) a sharp increase in the elastic and viscous moduli, (2) a transition peak recorded by differential scanning calorimetry, (3) formation of Maltese cross birefringence textures observed via polarizing optical microscopy, (4) a decrease in the interbilayer mean distance measured by small angle neutron scattering, and (5) an abrupt increase in the conductivity obstruction factor. In contrast to aqueous DDAB solutions, this surfactant forms a stable L(3) phase in EAN in a wide window of compositions and temperatures, which is potentially useful for the synthesis of nanoporous materials. To the best of our knowledge, this is the first evidence of the formation of the L(3) phase in an ionic liquid. PMID- 22047006 TI - Road traffic crashes managed by Rescue 1122 in Lahore, Pakistan. AB - The objective of this retrospective study was to describe demographic characteristics, injury patterns and causes of road traffic crashes (RTCs) managed by Rescue 1122 in Lahore, Pakistan during the period 2005-2010. In total 123,268 RTCs were reported and responded by Rescue 1122 ambulance service during the study period. Of the 132,504 victims of RTCs, there were 67% male and 33% female subjects, and the maximum share (65%) was reported among people aged 16-35 years. Motorcyclists were involved in 45% of crashes, with over-speeding (40%) found to be the major reason of these collisions. Similarly, minor injuries (65%) and fractures (25%) were the most reported outcome of these crashes. It is concluded that data from ambulance services, if appropriately collected, can provide valuable epidemiological information to monitor RTCs in developing countries. However, in Pakistan, the collection of data as well as the registration process needs further improvement. PMID- 22047007 TI - Prevention and management of transplant-associated diabetes. AB - INTRODUCTION: New-onset diabetes after transplantation (NODAT) is considered to be a major cause of cardiovascular disease and death among patients with a functioning allograft. A major challenge is to reduce the incidence of NODAT and to treat it optimally once it has occurred. AREAS COVERED: This review presents current data on how to prevent NODAT in patients at risk, with a focus on modifications in the immunosuppressive regimen. Current suggestions for detection and treatment of NODAT are also presented. EXPERT OPINION: Prevention of NODAT is possible by assessing the patient's glycemic risk prior to transplantation and tailoring the treatment (e.g., choice and dosage of immunosuppressive agents) after transplantation. An oral glucose tolerance test is still the gold standard to detect NODAT in patients at risk (prediabetes) but algorithms can be used to select those who should be tested. The treatment of NODAT involves a broad approach on risk factors for cardiovascular events and graft loss. Future studies on the use of oral hypoglycemic agents in NODAT are still needed. PMID- 22047005 TI - Vitamin D - roles in women's reproductive health? AB - In the past few years a growing interest in vitamin D can be observed in the lay and biomedical literature due to findings demonstrating a low vitamin D status in the population. In addition to its importance for the regulation of calcium and phosphorus homeostasis recent epidemiologic studies have observed relationships between low vitamin D levels and multiple disease states. This secosteroid hormone also regulates the expression of a large number of genes in reproductive tissues implicating a role for vitamin D in female reproduction. In this report we summarize the recent evidence that vitamin D status influences female reproductive and pregnancy outcomes. Human and animal data suggest that low vitamin D status is associated with impaired fertility, endometriosis and polycystic ovary syndrome. Evidence from observational studies shows higher rates of preeclampsia, preterm birth, bacterial vaginosis and gestational diabetes in women with low vitamin D levels. However, confirmation of experimental observations establishing an association of vitamin D deficiency with adverse reproductive outcomes by high quality observational and large-scale randomized clinical trials is still lacking. The determination of optimal 25(OH)D3 levels in the reproductive period and the amount of vitamin D supplementation required to achieve those levels for the numerous actions of vitamin D throughout a woman's life would have important public health implications. PMID- 22047008 TI - Density functional theory study of the oxidation of ammonia on the IrO2(110) surface. AB - In this study, we employed density functional theory (DFT) to investigate the oxidation of ammonia (NH(3)) on the IrO(2)(110) surface. We characterized the possible reaction pathways for the dehydrogenation of NH(x) species (x = 1-3) and for the formation of the oxidation products N(2), N(2)O, NO, NO(2), and H(2)O. The presence of oxygen atoms on coordinatively unsaturated sites (O(cus)) of the oxygen-rich IrO(2)(110) surface promotes the oxidation of NH(3) on the surface. In contrast, NH(3) molecules prefer undergoing desorption over oxidation on the stoichiometric IrO(2)(110) surface. Moreover, the O(cus) atoms are also the major oxidants leading to the formation of oxidation products; none of the oxidations mediated by the bridge oxygen atoms were favorable reactions. The energy barrier for formation of H(2)O as a gaseous oxidation product on the IrO(2)(110) surface is high (from 1.83 to 2.29 eV), potentially leading to the formation of nitrogen atom-containing products at high temperature. In addition, the selectivity toward the nitrogen-atom-containing products is dominated by the coverage of O(cus) atoms on the surface; for example, a higher coverage of O(cus) atoms results in greater production of nitrogen oxides (NO, NO(2)). PMID- 22047009 TI - Grahamines A-E, cyclobutane-centered tropane alkaloids from the aerial parts of Schizanthus grahamii. AB - Schizanthus grahamii is an endemic Chilean plant that is known to contain tropane alkaloids. Five new alkaloids, grahamines A-E (1-5), were isolated and characterized by extensive spectroscopic analysis. Their structures were determined to be 2-{[(3alpha-hydroxytropo-6beta-yl)oxy]carbonyl}-2-methyl-3 {[((6beta-angeloyloxy)-3alpha-yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylic acid (1), 2-{[(3alpha-hydroxytropo-6beta-yl)oxy]carbonyl}-2-methyl-3-{[((6beta tigloyloxy)-3alpha-yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylic acid (2), 1 methyl-2-{[(3alpha-hydroxytropo-6beta-yl)oxy]carbonyl}-4-{[((6beta-angeloyloxy) 3alpha-yl)oxy]carbonyl}-3-phenylcyclobutanecarboxylic acid (3), 1,2-bis{[(3alpha hydroxytropo-6beta-yl)oxy]carbonyl}-2-methyl-3-{[((6beta-angeloyloxy)-3alpha yl)oxy]carbonyl}-4-phenylcyclobutanecarboxylate (4), and 1-{[(3alpha mesaconyloxytropo-6beta-yl)oxy]carbonyl}-2-{[(3alpha-hydroxytropo-6beta yl)oxy]carbonyl}-2-methyl-3-{[((6beta-angeloyloxy)-3alpha-yl)oxy]carbonyl}-4 phenylcyclobutanecarboxylate (5). PMID- 22047010 TI - Fluorescence and visual detection of single nucleotide polymorphism using cationic conjugated polyelectrolyte. AB - We report a simple assay for visual detection of single nucleotide polymorphisms (SNPs) with good sensitivity and selectivity. The selectivity is determined by Escherichia coli (E. coli) DNA ligase mediated circular formation upon recognition of the point mutation on DNA targets. Rolling cycle amplification (RCA) of the perfect-matched DNA target is then initiated using the in situ formed circular template in the presence of Phi29 enzyme. Due to amplification of the DNA target, the RCA product has a tandem-repeated sequence, which is significantly longer than that for the SNP strand. Direct addition of a cationic conjugated polymer of poly[9,9'-bis(6'-(N,N,N-trimethylammonium)hexyl)fluorene-co 9,9'-bis(2-(2-(2-(N,N,N-trimethylammonium)ethoxyl)-ethoxy)-ethyl)fluorene tetrabromide] containing 20 mol% 2,1,3-benzothiadiazole (PFBT(20)) into the RCA solution leads to blue-whitish fluorescent color for SNP strand and yellowish fluorescent color for amplified DNA, due to PFBT(20)/DNA complexation induced intrachain/interchain energy transfer. To further improve the contrast for visual detection, FAM-labeled peptide nucleic acid (PNA) was hybridized to each amplified sequence, which is followed by the addition of poly{2,7-[9,9-bis(6' N,N,N-trimethylammoniumhexyl)]fluorene-co-2,5-difluoro-1,4-phenylene dibromide} (PFP). The PNA/DNA hybridization brings PFP and FAM-PNA into close proximity for energy transfer, and the solution fluorescent color appears green in the presence of target DNA with a detection limit of 1 nM, which is significantly improved as compared to that for most reported visual SNP assay. PMID- 22047011 TI - Carbon aerogel composites prepared by ambient drying and using oxidized polyacrylonitrile fibers as reinforcements. AB - Carbon fiber-reinforced carbon aerogel composites (C/CAs) for thermal insulators were prepared by copyrolysis of resorcinol-formaldehyde (RF) aerogels reinforced by oxidized polyacrylonitrile (PAN) fiber felts. The RF aerogel composites were obtained by impregnating PAN fiber felts with RF sols, then aging, ethanol exchanging, and drying at ambient pressure. Upon carbonization, the PAN fibers shrink with the RF aerogels, thus reducing the difference of shrinkage rates between the fiber reinforcements and the aerogel matrices, and resulting in C/CAs without any obvious cracks. The three point bend strength of the C/CAs is 7.1 +/- 1.7 MPa, and the thermal conductivity is 0.328 W m(-1) K(-1) at 300 degrees C in air. These composites can be used as high-temperature thermal insulators (in inert atmospheres or vacuum) or supports for phase change materials in thermal protection system. PMID- 22047012 TI - Folding-promoted TBACl-mediated chemo- and regioselective demethylations of methoxybenzene-based macrocyclic pentamers. AB - Tetrabutylammonium chloride (TBACl) salt alone has not been shown previously to be capable of removing methoxy groups. It is demonstrated here that the use of TBACl achieves efficient folding-promoted chemo- and regioselective demethylations, eliminating up to two out of five methyl groups situated in similar macrocyclic chemical microenvironments. PMID- 22047013 TI - A technical modification for percutaneous tracheostomy: prospective case series study on one hundred patients. AB - The purpose of this study is to describe a technical modification of percutaneous tracheostomy that combines principles of the Percu TwistTM and the Griggs-Portex(r) methods in a reusable kit. One hundred patients underwent the procedure. There were no false passage, tube misplacement, or deaths related to the procedure. There were two minor bleedings managed conservatively. The technical modification described in this study is safe and simple to execute. PMID- 22047014 TI - Fast MCMC sampling for hidden Markov Models to determine copy number variations. AB - BACKGROUND: Hidden Markov Models (HMM) are often used for analyzing Comparative Genomic Hybridization (CGH) data to identify chromosomal aberrations or copy number variations by segmenting observation sequences. For efficiency reasons the parameters of a HMM are often estimated with maximum likelihood and a segmentation is obtained with the Viterbi algorithm. This introduces considerable uncertainty in the segmentation, which can be avoided with Bayesian approaches integrating out parameters using Markov Chain Monte Carlo (MCMC) sampling. While the advantages of Bayesian approaches have been clearly demonstrated, the likelihood based approaches are still preferred in practice for their lower running times; datasets coming from high-density arrays and next generation sequencing amplify these problems. RESULTS: We propose an approximate sampling technique, inspired by compression of discrete sequences in HMM computations and by kd-trees to leverage spatial relations between data points in typical data sets, to speed up the MCMC sampling. CONCLUSIONS: We test our approximate sampling method on simulated and biological ArrayCGH datasets and high-density SNP arrays, and demonstrate a speed-up of 10 to 60 respectively 90 while achieving competitive results with the state-of-the art Bayesian approaches. AVAILABILITY: An implementation of our method will be made available as part of the open source GHMM library from http://ghmm.org. PMID- 22047015 TI - Feasibility and willingness-to-pay for integrated community-based tuberculosis testing. AB - BACKGROUND: Community-based screening for TB, combined with HIV and syphilis testing, faces a number of barriers. One significant barrier is the value that target communities place on such screening. METHODS: Integrated testing for TB, HIV, and syphilis was performed in neighborhoods identified using geographic information systems-based disease mapping. TB testing included skin testing and interferon gamma release assays. Subjects completed a survey describing disease risk factors, healthcare access, healthcare utilization, and willingness to pay for integrated testing. RESULTS: Behavioral and social risk factors among the 113 subjects were prevalent (71% prior incarceration, 27% prior or current crack cocaine use, 35% homelessness), and only 38% had a regular healthcare provider. The initial 24 subjects reported that they would be willing to pay a median $20 (IQR: 0-100) for HIV testing and $10 (IQR: 0-100) for TB testing when the question was asked in an open-ended fashion, but when the question was changed to a multiple-choice format, the next 89 subjects reported that they would pay a median $5 for testing, and 23% reported that they would either not pay anything to get tested or would need to be paid $5 to get tested for TB, HIV, or syphilis. Among persons who received tuberculin skin testing, only 14/78 (18%) participants returned to have their skin tests read. Only 14/109 (13%) persons who underwent HIV testing returned to receive their HIV results. CONCLUSION: The relatively high-risk persons screened in this community outreach study placed low value on testing. Reported willingness to pay for such testing, while low, likely overestimated the true willingness to pay. Successful TB, HIV, and syphilis integrated testing programs in high risk populations will likely require one visit diagnostic testing and incentives. PMID- 22047016 TI - TiO(2) nanoparticles induce oxidative DNA damage and apoptosis in human liver cells. AB - Titanium dioxide nanoparticles (TiO(2) NPs), widely used in consumer products, paints, pharmaceutical preparations and so on, have been shown to induce cytotoxicity, genotoxicity and carcinogenic responses in vitro and in vivo. The present study revealed that TiO(2) NPs induce significant (p < 0.05) oxidative DNA damage by the Fpg-Comet assay even at 1 ug/ml concentration. A corresponding increase in the micronucleus frequency was also observed. This could be attributed to the reduced glutathione levels with concomitant increase in lipid peroxidation and reactive oxygen species generation. Furthermore, immunoblot analysis revealed an increased expression of p53, BAX, Cyto-c, Apaf-1, caspase-9 and caspase-3 and decreased the level of Bcl-2 thereby indicating that apoptosis induced by TiO(2) NPs occurs via the caspase-dependent pathway. This study systematically shows that TiO(2) NPs induce DNA damage and cause apoptosis in HepG2 cells even at very low concentrations. Hence the use of such nanoparticles should be carefully monitored. PMID- 22047017 TI - The kinetics of cell surface receptor expression in children perinatally exposed to polychlorinated biphenyls. AB - Exposure to polychlorinated biphenyls (PCBs) during pre-natal and early life can alter normal immune system development. Blood specimens from newborns, 6-, and 16 month-old infants were collected in the Michalovce and Svidnik/Stropkov districts, areas with, respectively, high and low environmental PCB contamination, and lymphocyte receptor expression was evaluated by multi-color flow cytometry. The results indicate that the percentage of lymphoid dendritic cells (DC) and naive/resting T-lymphocytes were significantly increased at 6 months in Michalovce as compared to the same cell types in cord blood samples (p < 0.001), whereas natural regulatory T-lymphocytes and suppressor inducer T lymphocytes were reduced (p < 0.001). Overall, a positive linear correlation of terminally differentiated effector memory (TEM) T-lymphocyte population with age, but a negative linear correlation for myeloid DC from birth to 6-months in both regions were found. Michalovce samples indicated significantly higher expression of memory T-lymphocytes (birth, 6(th), and 16(th) month), TEM T-lymphocytes (birth and 6(th) month), and lymphoid DC (6(th) month) compared to the Svidnik/Stropkov regions. After adjustment for relevant covariates, such as maternal age, parity, season of birth, breastfeeding, birth weight, and gender, the myeloid DC, suppressor inducer T-lymphocytes, truly naive helper/inducer T lymphocytes, and TEM T-lymphocytes remained significantly different between districts in cord blood samples. The multivariate analysis models for 6- and 16 month samples showed district differences in all cellular determinants, except for lymphoid DC and macrophage-like cells. This study provides the first evidence that pre-natal and early post-natal exposure to PCBs affects the dynamics of cell surface receptor expression on lymphoid DC and DC-like cells, suggesting impaired immunologic development following pre-natal and early post-natal PCB exposure. PMID- 22047018 TI - Statement of retraction. PMID- 22047019 TI - Course and prognosis of recovery for chronic non-specific low back pain: design, therapy program and baseline data of a prospective cohort study. AB - BACKGROUND: There has been increasing focus on factors predicting the development of chronic musculoskeletal disorders. For patients already experiencing chronic non-specific low back pain it is also relevant to investigate which prognostic factors predict recovery. We present the design of a cohort study that aims to determine the course and prognostic factors for recovery in patients with chronic non-specific low back pain. METHODS/DESIGN: All participating patients were recruited (Jan 2003-Dec 2008) from the same rehabilitation centre and were evaluated by means of (postal) questionnaires and physical examinations at baseline, during the 2-month therapy program, and at 5 and 12 months after start of therapy. The therapy protocol at the rehabilitation centre used a bio psychosocial approach to stimulate patients to adopt adequate (movement) behaviour aimed at physical and functional recovery. The program is part of regular care and consists of 16 sessions of 3 hours each, over an 8-week period (in total 48 hours), followed by a 3-month self-management program. The primary outcomes are low back pain intensity, disability, quality of life, patient's global perceived effect of recovery, and participation in work. Baseline characteristics include information on socio-demographics, low back pain, employment status, and additional clinical items status such as fatigue, duration of activities, and fear of kinesiophobia. Prognostic variables are determined for recovery at short-term (5 months) and long-term (12 months) follow-up after start of therapy. DISCUSSION: In a routine clinical setting it is important to provide patients suffering from chronic non-specific low back pain with adequate information about the prognosis of their complaint. PMID- 22047020 TI - Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. AB - BACKGROUND: Urine within the urinary tract is commonly regarded as "sterile" in cultivation terms. Here, we present a comprehensive in-depth study of bacterial 16S rDNA sequences associated with urine from healthy females by means of culture independent high-throughput sequencing techniques. RESULTS: Sequencing of the V1V2 and V6 regions of the 16S ribosomal RNA gene using the 454 GS FLX system was performed to characterize the possible bacterial composition in 8 culture negative (<100,000 CFU/ml) healthy female urine specimens. Sequences were compared to 16S rRNA databases and showed significant diversity, with the predominant genera detected being Lactobacillus, Prevotella and Gardnerella. The bacterial profiles in the female urine samples studied were complex; considerable variation between individuals was observed and a common microbial signature was not evident. Notably, a significant amount of sequences belonging to bacteria with a known pathogenic potential was observed. The number of operational taxonomic units (OTUs) for individual samples varied substantially and was in the range of 20-500. CONCLUSIONS: Normal female urine displays a noticeable and variable bacterial 16S rDNA sequence richness, which includes fastidious and anaerobic bacteria previously shown to be associated with female urogenital pathology. PMID- 22047022 TI - Ruthenium-catalyzed meta sulfonation of 2-phenylpyridines. AB - A selective catalytic meta sulfonation of 2-phenylpyridines was found to occur in the presence of (arene)ruthenium(II) complexes upon reaction with sulfonyl chlorides. The 2-pyridyl group facilitates the formation of a stable Ru-C(aryl) sigma bond that induces a strong para-directing effect. Electrophilic aromatic substitution proceeds with the sulfonyl chloride to furnish a sulfone at the position meta to the chelating group. This new catalytic process offers access to atypical regioselectivity for reactions involving chelation-assisted cyclometalation. PMID- 22047023 TI - Impact of an individualist vs. collectivist context on the social valorization of internal explanations. AB - The theory of the norm of internality emphasizes the role of Western individualism in the normativity of internal explanations. The present study examines the link between the social value accorded to targets expressing internal vs. external explanations and individualist vs. collectivist contexts. Sixty-three male and female French management sciences students evaluated two targets (internal vs. external) in a simulated recruitment situation. The job vacancy was partially manipulated to create individualist vs. collectivist contexts. Participants were asked to state whether or not they would recruit the targets and to describe the targets on traits relating to social utility (market value) and social desirability (likeability). As expected, the results showed that the effect of the targets' internality on recruitment judgments and perceived social utility was stronger in the individualist context than in the collectivist context. However, the analysis also revealed that the participant's gender moderated the impact of the context on the evaluation of the targets. The results showed that the context strongly affected the men's judgments, whereas it had no effect on the women's judgments. PMID- 22047021 TI - Translesion DNA synthesis in the context of cancer research. AB - During cell division, replication of the genomic DNA is performed by high fidelity DNA polymerases but these error-free enzymes can not synthesize across damaged DNA. Specialized DNA polymerases, so called DNA translesion synthesis polymerases (TLS polymerases), can replicate damaged DNA thereby avoiding replication fork breakdown and subsequent chromosomal instability.We focus on the involvement of mammalian TLS polymerases in DNA damage tolerance mechanisms. In detail, we review the discovery of TLS polymerases and describe the molecular features of all the mammalian TLS polymerases identified so far. We give a short overview of the mechanisms that regulate the selectivity and activity of TLS polymerases. In addition, we summarize the current knowledge how different types of DNA damage, relevant either for the induction or treatment of cancer, are bypassed by TLS polymerases. Finally, we elucidate the relevance of TLS polymerases in the context of cancer therapy. PMID- 22047024 TI - Barriers to physical activity in older adults in Germany: a cross-sectional study. AB - BACKGROUND: Data on barriers to physical activity in older adults in Germany are scarce. The aim of this study was to analyse barriers to physical activity in a cohort of older adults, allowing comparisons between men and women, and age groups. METHODS: 1,937 older adults with a median age of 77 (range 72-93) years (53.3% female) took part in the 7-year follow-up telephone interviews of the getABI cohort. Participants who stated that they did not get enough physical activity were surveyed with respect to barriers to physical activity. Barriers were analysed for all respondents, as well as by sex and age group for cases with complete data. Multivariate logistic regression analysis was performed to evaluate differences between sexes and age groups. The level of significance (alpha < 0.05) was adjusted for multiple testing according to Bonferroni (p < .004). RESULTS: 1,607 (83.0%) participants stated that they were sufficiently physically active. 286 participants rated their physical activity as insufficient and responded to questions on barriers to physical activity completely. The three most frequently cited barriers were poor health (57.7%), lack of company (43.0%), and lack of interest (36.7%). Lack of opportunities for sports or leisure activities (30.3% vs. 15.6%), and lack of transport (29.0% vs. 7.1%) were more frequently stated by female respondents than male respondents. These differences between men and women were significant (p = .003; p < .001) after adjustment for respondents' age. Analyses by age groups revealed that poor health was more frequently considered a barrier to physical activity by participants aged 80+ years compared to the younger age group (71.1% vs. 51.5%). This age-dependent difference was significant (p = .002) irrespective of the participants' sex. CONCLUSIONS: The present study provides relevant data on barriers to physical activity in older adults. By revealing appreciable differences between men and women, and age groups, this study has implications for efforts to increase older adults' physical activity. Promotion and intervention strategies should consider the barriers and tailor measures to the specific needs of older adults in order to reduce their constraints to physical activity. PMID- 22047025 TI - Enantiomer resolution by pressure increase: inferences from experimental and topological results for the binary enantiomer system (R)- and (S)-mandelic acid. AB - In pharmacy, racemic compounds are often problematic, because generally only one of the enantiomers possesses therapeutic activity and it is often difficult to separate them. Even though this problem is likely as old as the pharmaceutical industry, one thermodynamically obvious way of separating racemic crystals has never been studied experimentally, which is by using pressure. Data have been obtained on the equilibria of the (R)- and (S)-mandelic acid system as a function of pressure and temperature. With the use of thermodynamic arguments including the Clapeyron, Schroder, and Prigogine-Defay equations, it has been demonstrated that the conglomerate (crystals of separated enantiomers) becomes more stable than the racemic compound at approximately 0.64 GPa and 460 K. Even though this pressure is still higher than at the bottom of the Mariana Trench, there are no technical obstacles to produce such conditions, making pressure a viable option for separating enantiomers. PMID- 22047028 TI - Development of a multilevel approach for the evaluation of nanomaterials' toxicity. AB - AIM: To develop a multilevel approach that includes different toxicity tests and gene-expression studies for toxicity evaluation of engineered nanomaterials developed for biomedical applications. MATERIALS & METHODS: K-562, MCF-7 and U 937 human-derived cell lines were used as models for in vitro toxicity tests. These tests included viability assays (3-[4,5-dimethylthiazol-2-yl]-5-[3 carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium [MTS] assay); evaluation of apoptosis/necrosis by propidium iodide staining and DNA laddering assay; evaluation of mitochondrial toxicity (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl benzimidazolcarbocyanine iodide [JC-1] assay); transmission electron microscopy analysis and gene expression analysis by DNA microarray. For in vivo toxicity evaluation, Swiss mice were used for monitoring acute or chronic effects. Two superparamagnetic contrast agents approved for human use (Resovist and Primovist) and two new lanthanide-based luminescent nanoparticles were tested. RESULTS & DISCUSSION: The nanomaterials approved for human use did not show significant toxicities in our assays. Toxicity studies performed on lanthanide-based nanoparticles (EDTA120 and EDTA120D) complexed with the chelating agent EDTA revealed that these nanomaterials induced necrosis in U-937 and K-562 cells while no toxicity was observed in MCF-7 cells. Moreover, no in vivo effects have been observed. The comparative analysis of the nanomaterials and their separated components showed that the toxicity in U-937 and K-562 cells was mainly due to the presence of EDTA. CONCLUSION: The multilevel approach proved to be useful for nanomaterial toxicity characterization. In particular, for the lanthanide-based nanoparticles tested in this work, the EDTA was identified as the main cause of the toxicity in vitro, suggesting a possible applicability of these nanoparticle suspensions for in vivo optical imaging. PMID- 22047027 TI - Cancer control and prevention by nutrition and epigenetic approaches. AB - SIGNIFICANCE: Epigenetics involves alterations in gene expression without changing the nucleotide sequence. Because some epigenetic changes can be reversed chemically, epigenetics has tremendous implications for disease intervention and treatment. RECENT ADVANCES: After epigenetic components in cancer were characterized, genes and pathways are being characterized in other diseases such as diabetes, obesity, and neurological disorders. Observational, experimental, and clinical studies in different diseases have shown that nutrients influence epigenetic regulation. Nutrients such as folic acid that supply methyl groups have been shown to have a protective effect in colon cancer. CRITICAL ISSUES: Identifying steps during epigenetic regulation and developing intervention and treatment agents are the critical issues in the field. FUTURE DIRECTIONS: Following completion and validation of key observational studies in nutritional epigenetics, strategies can be developed for cancer control and treatment. PMID- 22047030 TI - Editorial. PMID- 22047029 TI - Mechanism of titania deposition into cylindrical poly(styrene-block-4 vinyl pyridine) block copolymer templates. AB - A simple and effective way for TiO(2) to be deposited on silicon or indium tin oxide (ITO) substrates has been achieved by using a poly(styrene-block-4-vinyl pyridine) (PS-b-P4VP) block copolymer template. In particular, a mechanism for the formation of TiO(2) within the P4VP phase was developed. Within this model, the TiO(2) deposition occurs by swelling of the protonated P4VP segments followed by transport of Ti precursor, probably protonated Ti(OH)(4) given the low pH conditions used, into the swollen P4VP followed by condensation into TiO(2) during the heating/plasma etch processes. TiO(2) nanostructure morphology is affected by pH and deposition temperatures, because these parameters affect the degree of protonation of P4VP segments and diffusion of the titanium(IV) bis(ammonium lactato)dihydroxide (TALH) precursor into the film. A pH range of 2.1-2.5 for silicon substrates and pH = 2.1 for ITO substrates gave the narrower TiO(2) nanostructures distributions, and deposition at 70 degrees C gave TiO(2) nanostructures with more regular arrangements and smoother surface than those deposited at room temperature. The use of 1,4-diiodobutane as a P4VP cross linking compound is demonstrated to be a critical parameter for maintaining good cylindrical surface morphology for both the block copolymer template and the TiO(2) nanostructures. PMID- 22047031 TI - Miscellaneous. PMID- 22047032 TI - Erratum. PMID- 22047035 TI - A step beyond the Feltham-Enemark notation: spectroscopic and correlated ab initio computational support for an antiferromagnetically coupled M(II)-(NO)- description of Tp*M(NO) (M = Co, Ni). AB - Multiple spectroscopic and computational methods were used to characterize the ground-state electronic structure of the novel {CoNO}(9) species Tp*Co(NO) (Tp* = hydro-tris(3,5-Me(2)-pyrazolyl)borate). The metric parameters about the metal center and the pre-edge region of the Co K-edge X-ray absorption spectrum were reproduced by density functional theory (DFT), providing a qualitative description of the Co-NO bonding interaction as a Co(II) (S(Co) = 3/2) metal center, antiferromagnetically coupled to a triplet NO(-) anion (S(NO) = 1), an interpretation of the electronic structure that was validated by ab initio multireference methods (CASSCF/MRCI). Electron paramagnetic resonance (EPR) spectroscopy revealed significant g-anisotropy in the S = 1/2 ground state, but the linear-response DFT performed poorly at calculating the g-values. Instead, CASSCF/MRCI computational studies in conjunction with quasi-degenerate perturbation theory with respect to spin-orbit coupling were required for obtaining accurate modeling of the molecular g-tensor. The computational portion of this work was extended to the diamagnetic Ni analogue of the Co complex, Tp*Ni(NO), which was found to consist of a Ni(II) (S(Ni) = 1) metal center antiferromagnetically coupled to an S(NO) = 1 NO(-). The similarity between the Co and Ni complexes contrasts with the previously studied Cu analogues, for which a Cu(I) bound to NO(0) formulation has been described. This discrepancy will be discussed along with a comparison of the DFT and ab initio computational methods for their ability to predict various spectroscopic and molecular features. PMID- 22047036 TI - Rapid deposition of transparent super-hydrophobic layers on various surfaces using microwave plasma. AB - We report herein on a very fast and simple process for the fabrication of transparent superhydrophobic surfaces by using microwave (MW) plasma. It was found that the reaction of various organic liquids in MW argon plasma yields hydrophobic polymeric layers on a large assortment of surfaces, including glass, polymeric surfaces, ceramics, metals, and even paper. In most cases, these polymers are deposited as a rough layer composed of 10-15 nm nanoparticles (NPs). This roughness, together with the chemical hydrophobic nature of the coated materials, is responsible for the superhydrophobic nature of the surface. The typical reaction time of the coating procedure was 1-10 s. The stability of these superhydrophobic surfaces was examined outdoors, and was found to last 2-5 days under direct exposure to the environment and to last 2 months when the sample was protected by a quartz cover. A detailed characterization study of the chemical composition of the layers followed using XPS, solid-state NMR, and IR measurements. Modifications were introduced in the products leading to a substantial improvement in the stability of the products outdoors. PMID- 22047037 TI - A powerful palladium-catalyzed multicomponent process for the preparation of oxazolines and benzoxazoles. AB - Efficient and convenient three-component couplings of an aryl halide, isocyanide, and an amino alcohol under palladium catalysis provide a range of oxazolines and benzoxazoles in excellent yield. PMID- 22047038 TI - Intra aortic balloon pump: literature review of risk factors related to complications of the intraaortic balloon pump. AB - The increasing use of the intra aortic balloon pump is attributed to the relatively easy percutaneous insertion and the low threshold of use over the past few years, especially in elderly patients with multi-vessel diseases and an affected ejection fraction.Unfortunately, the clinical assessment of the complications associated to the use of this supporting device, underestimates the frequency of such complications.This report has looked at the current literature and attempt to identify incremental risk factors related to the development of adverse effects during support with an intaaortic balloon pump.The paper concludes that in contrary to early reports, newer studies have shown that complications following intraaortic balloon pump treatment, is decreasing. Moreover the literature suggests that the thrombosis and infective complications are relevant to the duration of the pump treatment, while the ischemic problems of the limbs are mostly linked to the atherosclerotic status of the common femoral artery. PMID- 22047039 TI - Evolutionary history of barley cultivation in Europe revealed by genetic analysis of extant landraces. AB - BACKGROUND: Understanding the evolution of cultivated barley is important for two reasons. First, the evolutionary relationships between different landraces might provide information on the spread and subsequent development of barley cultivation, including the adaptation of the crop to new environments and its response to human selection. Second, evolutionary information would enable landraces with similar traits but different genetic backgrounds to be identified, providing alternative strategies for the introduction of these traits into modern germplasm. RESULTS: The evolutionary relationships between 651 barley landraces were inferred from the genotypes for 24 microsatellites. The landraces could be divided into nine populations, each with a different geographical distribution. Comparisons with ear row number, caryopsis structure, seasonal growth habit and flowering time revealed a degree of association between population structure and phenotype, and analysis of climate variables indicated that the landraces are adapted, at least to some extent, to their environment. Human selection and/or environmental adaptation may therefore have played a role in the origin and/or maintenance of one or more of the barley landrace populations. There was also evidence that at least some of the population structure derived from geographical partitioning set up during the initial spread of barley cultivation into Europe, or reflected the later introduction of novel varieties. In particular, three closely-related populations were made up almost entirely of plants with the daylength nonresponsive version of the photoperiod response gene PPD-H1, conferring adaptation to the long annual growth season of northern Europe. These three populations probably originated in the eastern Fertile Crescent and entered Europe after the initial spread of agriculture. CONCLUSIONS: The discovery of population structure, combined with knowledge of associated phenotypes and environmental adaptations, enables a rational approach to identification of landraces that might be used as sources of germplasm for breeding programs. The population structure also enables hypotheses concerning the prehistoric spread and development of agriculture to be addressed. PMID- 22047040 TI - Structures, energies, bonding, and NMR properties of pnicogen complexes H2XP:NXH2 (X ? H, CH3, NH2, OH, F, Cl). AB - Ab initio calculations have been carried out in a systematic investigation of P...N pnicogen complexes H(2)XP:NXH(2) for X ? H, CH(3), NH(2), OH, F, and Cl, as well as selected complexes with different substituents X bonded to P and N. Binding energies for complexes H(2)XP:NXH(2) range from 8 to 27 kJ mol(-1) and increase to 39 kJ mol(-1) for H(2)FP:N(CH(3))H(2). Equilibrium structures have a nearly linear A-P-N arrangement, with A being the atom directly bonded to P. Binding energies correlate with intermolecular N-P distances as well as with bonding parameters obtained from AIM and SAPT analyses. Complexation increases (31)P chemical shieldings in complexes with binding energies greater than 19 kJ mol(-1). One-bond spin-spin coupling constants (1p)J(N-P) across the pnicogen interaction exhibit a quadratic dependence on the N-P distance for complexes H(2)XP:NXH(2), similar to the dependence of (2h)J(X-Y) on the X-Y distance for complexes with X-H...Y hydrogen bonds. However, when the mixed complexes H(2)XP:NX'H(2) are included, the curvature of the trendline changes and the good correlation between (1p)J(N-P) and the N-P distance is lost. PMID- 22047041 TI - Biofilm and planktonic pneumococci demonstrate disparate immunoreactivity to human convalescent sera. AB - BACKGROUND: Streptococcus pneumoniae (the pneumococcus) is the leading cause of otitis media, community-acquired pneumonia (CAP), sepsis, and meningitis. It is now evident that S. pneumoniae forms biofilms during nasopharyngeal colonization; the former which facilitates persistence, the latter, a prerequisite for subsequent development of invasive disease. Proteomic evaluation of S. pneumoniae suggests the antigen profile available for host-recognition is altered as a consequence of biofilm growth. This has potentially meaningful implications in regards to adaptive immunity and protection from disseminated disease. We therefore examined the antigen profile of biofilm and planktonic pneumococcal cell lysates, tested their reactivity with human convalescent sera and that generated against biofilm pneumococci, and examined whether immunization with biofilm pneumococci protected mice against infectious challenge. RESULTS: Biofilm pneumococci have dramatically altered protein profiles versus their planktonic counterparts. During invasive disease the humoral immune response is skewed towards the planktonic protein profile. Immunization with biofilm bacteria does not elicit a strong-cross-reactive humoral response against planktonic bacteria nor confer resistance against challenge with a virulent isolate from another serotype. We identified numerous proteins, including Pneumococcal serine-rich repeat protein (PsrP), which may serve as a protective antigens against both colonization and invasive disease. CONCLUSION: Differential protein production by planktonic and biofilm pneumococci provides a potential explanation for why individuals remain susceptible to invasive disease despite previous colonization events. These findings also strongly suggest that differential protein production during colonization and disease be considered during the selection of antigens for any future protein vaccine. PMID- 22047042 TI - Porphyromonas gingivalis accelerates atherosclerosis in C57BL/6 mice fed a high fat diet. AB - OBJECTIVE: Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in atherosclerotic apo E-deficient mice. Here, we investigated whether repeated P. gingivalis injection affected the inflammatory and atherosclerotic responses of C57BL/6 mice fed a high-fat diet (HFD). MATERIALS AND METHODS: Eight-week-old C57BL/6 mice fed either HFD or a regular chow diet (RD) were inoculated intravenously with P. gingivalis or phosphate-buffered saline three times per week for 10 weeks and sacrificed at 19 weeks of age. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and the serum cytokine and C-reactive protein (CRP) levels were determined. RESULTS: Long-term HFD feeding as compared to RD feeding led to a slight increase in atheromatous lesions in the aortic sinus as well as increases in the levels of serum monocyte chemoattractant protein 1. Further, P. gingivalis injection significantly enhanced the formation of atherosclerotic plaque, and increased CRP and inflammatory cytokine levels, in mice fed the HFD, although no further increase in LDL was observed. CONCLUSION: These results suggest that bacteremia-induced by repeated injection with P. gingivalis accelerates atherosclerosis in normal C57BL/6 mice by initiating inflammation, and is therefore implicated in chronic infection-related pathogenicity. PMID- 22047043 TI - Dynamic structure factor for large aggregate clusters with internal motions: a self-consistent light-scattering study on conjugated polymer solutions. AB - The aggregation properties of a standard conjugated polymer, poly(2-methoxy-5-(2' ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV), in two distinct solvents (chloroform and toluene) and a range of polymer concentrations (c = 0.1-3 mg/mL) have been unequivocally resolved using combined dynamic and static light scatterings (DLS/SLS). The prime challenges for analyzing this peculiar, practically important, solution system arise from the wide size distribution and unknown aggregate morphology, as well as pronounced interferences between translational and internal motions of aggregate clusters of considerably varying size. To cope with these central difficulties, we propose a self-consistent formulation for analyzing the dynamic structure factor in DLS experiment by extending an existing theory on free-draining bead-spring chains that explicitly accounts for internal fluctuations, along with two candidate form factors on Gaussian coil and rigid sphere, respectively, serving as two limiting cases to be discriminated in combined DLS and SLS measurements. Given that no accessibility to ultrasmall angular resolutions is a prerequisite, the suggested protocol can readily be carried out in conventional light-scattering apparatus. The present analyses unanimously support the rigid-sphere form factor in describing the entire set of light-scattering data on MEH-PPV solutions, differing from early small-angle neutron/X-ray scattering interpretations suggesting certain 2D fractal structures for the aggregation network. Scrutiny into the interior dynamics of aggregate clusters further disclosed that the segmental motions are noticeably more suppressed than for usual, nonaggregated polymer solutions, and no existing theories based on the bead-spring picture can yet capture the observed scaling behavior as manifested by the present data. Accordingly, we report several first-revealed properties of MEH-PPV solutions on the aggregate morphology, the size distribution (and mean size), mean aggregation number, and interior segmental dynamics, which serve as valuable information for linking solution properties with those for dried thin films in contemporary applications with conducting conjugated polymers. PMID- 22047044 TI - Correspondence between salivary proteomic pattern and clinical course in primary Sjogren syndrome and non-Hodgkin's lymphoma: a case report. AB - BACKGROUND: In the last years human proteomic has represented a promising tool to promote the communication between basic and clinical science. METHODS: To explore the correspondence between salivary proteomic profile and clinical response, herein, we used a proteomic approach to analyse the whole saliva of a patient with primary Sjogren's Syndrome (pSS) and non-Hodgkin's-MALT type parotid lymphoma before, during and after a standard treatment with cyclophosphamide (CTX) and rituximab (RTX). To identify any discriminatory therapeutic salivary biomarker patient's whole saliva was collected at the baseline, after the fourth infusion of rituximab, and on remission and analysed combining two-dimensional electrophoresis (2DE) and MALDI-TOF/TOF mass spectrometry. RESULTS: Proteomic results obtained from the comparison of salivary samples indicated several qualitative and quantitative modifications in the salivary expression of putative albumin, immunoglobulin J chain, Ig kappa chain C region, alpha-1-antitrypsin, haptoglobin and Ig alpha-1 chain C region. CONCLUSION: This study suggests that clinical and functional changes of the salivary glands driven by autoimmune and lymphoproliferative processes might be reflected in patients' whole saliva proteins, shedding new light on the potential usefulness of salivary proteomic analysis in the identification of prognostic and therapeutic biomarkers for patients with pSS and non Hodgkin's lymphomas. PMID- 22047045 TI - Multivariate modelling with (1)H NMR of pleural effusion in murine cerebral malaria. AB - BACKGROUND: Cerebral malaria is a clinical manifestation of Plasmodium falciparum infection. Although brain damage is the predominant pathophysiological complication of cerebral malaria (CM), respiratory distress, acute lung injury, hydrothorax/pleural effusion are also observed in several cases. Immunological parameters have been assessed in pleural fluid in murine models; however there are no reports of characterization of metabolites present in pleural effusion. METHODS: 1H NMR of the sera and the pleural effusion of cerebral malaria infected mice were analyzed using principal component analysis, orthogonal partial least square analysis, multiway principal component analysis, and multivariate curve resolution. RESULTS: It has been observed that there was 100% occurrence of pleural effusion (PE) in the mice affected with CM, as opposed to those are non cerebral and succumbing to hyperparasitaemia (NCM/HP). An analysis of 1H NMR and SDS-PAGE profile of PE and serum samples of each of the CM mice exhibited a similar profile in terms of constituents. Multivariate analysis on these two classes of biofluids was performed and significant differences were detected in concentrations of metabolites. Glucose, creatine and glutamine contents were high in the PE and lipids being high in the sera. Multivariate curve resolution between sera and pleural effusion showed that changes in PE co-varied with that of serum in CM mice. The increase of glucose in PE is negatively correlated to the glucose in serum in CM as obtained from the result of multiway principal component analysis. CONCLUSIONS: This study reports for the first time, the characterization of metabolites in pleural effusion formed during murine cerebral malaria. The study indicates that the origin of PE metabolites in murine CM may be the serum. The loss of the components like glucose, glutamine and creatine into the PE may worsen the situation of patients, in conjunction with the enhanced glycolysis, glutaminolysis and increased activity of creatine phophokinase which are already reported characteristic pathophysiological features of malaria. PMID- 22047046 TI - Efficacy of tranexamic acid in reducing blood loss in posterior lumbar spine surgery for degenerative spinal stenosis with instability: a retrospective case control study. AB - BACKGROUND: Degenerative spinal stenosis and instability requiring multilevel spine surgery has been associated with large blood losses. Factors that affect perioperative blood loss include time of surgery, surgical procedure, patient height, combined anterior/posterior approaches, number of levels fused, blood salvage techniques, and the use of anti-fibrinolytic medications. This study was done to evaluate the efficacy of tranexamic acid in reducing blood loss in spine surgery. METHODS: This retrospective case control study includes 97 patients who had to undergo surgery because of degenerative lumbar spinal stenosis and instability. All operations included spinal decompression, interbody fusion and posterior instrumentation (4-5 segments). Forty-six patients received 1 g tranexamic acid intravenous, preoperative and six hours and twelve hours postoperative; 51 patients without tranexamic acid administration were evaluated as a control group. Based on the records, the intra- and postoperative blood losses were measured by evaluating the drainage and cell saver systems 6, 12 and 24 hours post operation. Additionally, hemoglobin concentration and platelet concentration were reviewed. Furthermore, the number of red cell transfusions given and complications associated with tranexamic acid were assessed. RESULTS: The postoperative hemoglobin concentration demonstrated a statistically significant difference with a p value of 0.0130 showing superiority for tranexamic acid use (tranexamic acid group: 11.08 g/dl, SD: 1.68; control group: 10.29 g/dl, SD: 1.39). The intraoperative cell saver volume and drainage volume after 24 h demonstrated a significant difference as well, which indicates a less blood loss in the tranexamic acid group than the control group. The postoperative drainage volume at12 hours showed no significant differences; nor did the platelet concentration Allogenic blood transfusion (two red cell units) was needed for eight patients in the tranexamic acid group and nine in the control group because of postoperative anemia. Complications associated with the administration of tranexamic acid, e.g. renal failure, deep vein thrombosis or pulmonary embolism did not occur. CONCLUSIONS: This study suggests a less blood loss when administering tranexamic acid in posterior lumbar spine surgery as demonstrated by the higher postoperative hemoglobin concentration and the less blood loss. But given the relatively small volume of blood loss in the patients of this study it is underpowered to show a difference in transfusion rates. PMID- 22047047 TI - Factors associated with paradoxical immune response to antiretroviral therapy in HIV infected patients: a case control study. AB - BACKGROUND: A paradoxical immunologic response (PIR) to Highly Active Antiretroviral Therapy (HAART), defined as viral suppression without CD4 cell count improvement, has been reported in the literature as 8 to 42%, around 15% in most instances. The present study aims to determine, in a cohort of HIV infected patients in Brazil, what factors were independently associated with such a discordant response to HAART. METHODS: A case-control study (1:4) matched by gender was conducted among 934 HIV infected patients on HAART in Brazil. CASES: patients with PIR, defined as CD4 < 350 cells/mm(3) (hazard ratio for AIDS or death of at least 8.5) and undetectable HIV viral load on HAART for at least one year. CONTROLS: similar to cases, but with CD4 counts >= 350 cells/mm(3). Eligibility criteria were applied. Data were collected from medical records using a standardized form. Variables were introduced in a hierarchical logistic regression model if a p-value < 0.1 was determined in a bivariate analysis. RESULTS: Among 934 patients, 39 cases and 160 controls were consecutively selected. Factors associated with PIR in the logistic regression model were: total time in use of HAART (OR 0.981; CI 95%: 0.96-0.99), nadir CD4-count (OR 0.985; CI 95%: 0.97-0.99), and time of undetectable HIV viral load (OR 0.969; CI 95%: 0.94-0.99). CONCLUSIONS: PIR seems to be related to a delay in the management of immunodeficient patients, as shown by its negative association with nadir CD4-count. Strategies should be implemented to avoid such a delay and improve the adherence to HAART as a way to implement concordant responses. PMID- 22047048 TI - Type-2 isopentenyl diphosphate isomerase: evidence for a stepwise mechanism. AB - Isopentenyl diphosphate isomerase (IDI) catalyzes the interconversion of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). These two molecules are the building blocks for construction of isoprenoid carbon skeletons in nature. Two structurally unrelated forms of IDI are known. A variety of studies support a proton addition/proton elimination mechanism for both enzymes. During studies with Thermus thermophilus IDI-2, we discovered that the olefinic hydrogens of a vinyl thiomethyl analogue of isopentenyl diphosphate exchanged with solvent when the enzyme was incubated with D(2)O without concomitant isomerization of the double bond. These results suggest that the enzyme-catalyzed isomerization reaction is not concerted. PMID- 22047049 TI - Mossbauer and EPR study of iron in vacuoles from fermenting Saccharomyces cerevisiae. AB - Vacuoles were isolated from fermenting yeast cells grown on minimal medium supplemented with 40 MUM (57)Fe. Absolute concentrations of Fe, Cu, Zn, Mn, Ca, and P in isolated vacuoles were determined by ICP-MS. Mossbauer spectra of isolated vacuoles were dominated by two spectral features: a mononuclear magnetically isolated high-spin (HS) Fe(III) species coordinated primarily by hard/ionic (mostly or exclusively oxygen) ligands and superparamagnetic Fe(III) oxyhydroxo nanoparticles. EPR spectra of isolated vacuoles exhibited a g(ave) ~ 4.3 signal typical of HS Fe(III) with E/D ~ 1/3. Chemical reduction of the HS Fe(III) species was possible, affording a Mossbauer quadrupole doublet with parameters consistent with O/N ligation. Vacuolar spectral features were present in whole fermenting yeast cells; however, quantitative comparisons indicated that Fe leaches out of vacuoles during isolation. The in vivo vacuolar Fe concentration was estimated to be ~1.2 mM while the Fe concentration of isolated vacuoles was ~220 MUM. Mossbauer analysis of Fe(III) polyphosphate exhibited properties similar to those of vacuolar Fe. At the vacuolar pH of 5, Fe(III) polyphosphate was magnetically isolated, while at pH 7, it formed nanoparticles. This pH-dependent conversion was reversible. Fe(III) polyphosphate could also be reduced to the Fe(II) state, affording similar Mossbauer parameters to that of reduced vacuolar Fe. These results are insufficient to identify the exact coordination environment of the Fe(III) species in vacuoles, but they suggest a complex closely related to Fe(III) polyphosphate. A model for Fe trafficking into/out of yeast vacuoles is proposed. PMID- 22047050 TI - The impact of initiating biphasic human insulin 30 therapy in type 2 diabetes patients after failure of oral antidiabetes drugs. AB - BACKGROUND: The present study evaluated the efficacy of biphasic human insulin 30 (BHI 30) in type 2 diabetes patients who had failed in therapy with two or more oral antidiabetes drugs (OADs). METHODS: This open-label, nonrandomized, 4-month, multicenter, clinical observational study was conducted in Shanghai, China. A total of 660 insulin-naive type 2 diabetes patients with poor glycemic control (glycosylated hemoglobin [HbA1c] >=7.5%), despite treatment with two or more OADs for more than 6 months, were recruited and received BHI 30 monotherapy or BHI 30 plus OAD(s) (metformin only, alpha-glucosidase inhibitor only, or both). RESULTS: Among the 660 subjects, 644 completed the 4-month study. At the end of the study, the median level of HbA1c decreased by 2.0% (from 9.1% to 7.0%) in the BHI 30 monotherapy group and also 2.0% (from 9.5% to 7.3%) in the BHI 30 plus OAD group. More patients achieved the HbA1c <7.0% target in the BHI 30 monotherapy group than in the BHI 30 plus OAD(s) group (47.9% vs. 35.3%, P=0.002). Compared with the expenses of the prior treatment strategy, the median daily cost decreased by 39.8% (4.5 yuan, Chinese RMB) at the end point in the BHI 30 monotherapy group but increased by 20.0% (2.2 yuan) in the BHI 30 plus OAD(s) group (P<0.0001). Moreover, patients in the BHI 30 plus OAD(s) group had fewer minor hypoglycemic episodes than in the BHI 30 monotherapy group (mean of 1.06 vs. 2.77 per patient per year, P<0.0001). CONCLUSIONS: Short-term BHI 30 therapy can improve glycemic control in insulin-naive type 2 diabetes patients after failure of two or more OADs. With higher baseline glucose level, the BHI 30 plus OAD(s) group had lower pharmacoeconomic efficacy than the BHI 30 monotherapy group despite having fewer hypoglycemia events. PMID- 22047051 TI - A comparison of average daily risk range scores for young children with type 1 diabetes mellitus using continuous glucose monitoring and self-monitoring data. AB - BACKGROUND: Young children with type 1 diabetes are vulnerable to glycemic excursion. Continuous glucose monitoring (CGM), combined with variability statistics, can offer a richer and more complete picture of glycemic variability in young children. In particular, we present data for the Average Daily Risk Range (ADRR) and compare ADRR scores calculated using CGM versus self-monitoring of blood glucose (SMBG) data for young children. METHODS: CGM and SMBG data from 48 young children with type 1 diabetes (mean age, 5.1 years) were used to calculate two separate ADRR scores, using SMBG data (ADRRs) and CGM data (ADRRc), for each child. Additionally, we calculated mean amplitude of glycemic excursion (MAGE) scores for children to examine the concurrent validity of the ADRRs and ADRRc. RESULTS: Young children's mean ADRRc score was significantly greater than their ADRRs score (55+/-12 and 46+/-11, respectively; P<0.001). In addition, 74% of the time the children's ADRRc score reflected greater variability risk than their ADRRs score. Examining the concurrent validity, children's ADRRc scores correlated positively with MAGE scores calculated using their CGM and SMBG data, whereas their ADRRs scores only correlated with MAGE scores calculated using SMBG. CONCLUSIONS: ADRR scores generated for young children with type 1 diabetes demonstrate a high risk for glucose variability, but ADRR scores generated from CGM data may provide a more sensitive measure of variability than ADRR scores generated from SMBG. In young children with type 1 diabetes, ADRR scores calculated from CGM data may be superior to scores calculated from SMBG for measuring risk of excursion. PMID- 22047052 TI - Development of a novel three-dimensional, automatable and integrated bioprocess for the differentiation of embryonic stem cells into pulmonary alveolar cells in a rotating vessel bioreactor system. AB - Application of stem cells for cell therapy of respiratory diseases is a developing field. We have previously established several protocols for the differentiation of embryonic stem cells (ESC) into alveolar epithelial cells, which require a high degree of operator interference and result in a low yield of target cells. Herein, we have shown that, by provision of a medium conditioned using A549 cells and by integration of classic steps of ESC differentiation into a single step through encapsulation in hydrogels (three-dimensional) and culture in a rotary bioreactor, murine ESC (mESC) could be directed to differentiate into distal respiratory epithelial cells. Type I and II pneumocytes (with a yield of 50% for type II) and Clara cells were demonstrated by the expression of aquaporin 5, surfactant protein C, and Clara cell secretory protein, respectively. We identified target cells as early as day 5 of culture and stably maintained our differentiated cells in vitro for 100 days. Electron microscopy demonstrated microvilli and intracellular lamellar bodies (LB), and fluorescent staining confirmed the active process of exocytosis of these LB in differentiated type II cells. When these cells were decapsulated and cultured in static conditions in flask cultures (two-dimensional), they retained their characteristic type II phenotype and morphology. In conclusion, our protocol offers integrated bioprocessing, shorter time of differentiation, lower cost, no use of growth factors, high reproducibility, and high phenotypic and functional stability, as well as being amenable to automation and being scalable, which would move this field closer to future clinical applications. PMID- 22047053 TI - NIST gold nanoparticle reference materials do not induce oxidative DNA damage. AB - One primary challenge in nanotoxicology studies is the lack of well-characterised nanoparticle reference materials which could be used as positive or negative nanoparticle controls. The National Institute of Standards and Technology (NIST) has developed three gold nanoparticle (AuNP) reference materials (10, 30 and 60 nm). The genotoxicity of these nanoparticles was tested using HepG2 cells and calf-thymus DNA. DNA damage was assessed based on the specific and sensitive measurement of four oxidatively-modified DNA lesions (8-hydroxy-2' deoxyguanosine, 8-hydroxy-2'-deoxyadenosine, (5'S)-8,5'-cyclo-2'-deoxyadenosine and (5'R)-8,5'-cyclo-2'-deoxyadenosine) using liquid chromatography/tandem mass spectrometry. Significantly elevated, dose-dependent DNA damage was not detected at concentrations up to 0.2 MUg/ml, and free radicals were not detected using electron paramagnetic resonance spectroscopy. These data suggest that the NIST AuNPs could potentially serve as suitable negative-control nanoparticle reference materials for in vitro and in vivo genotoxicity studies. NIST AuNPs thus hold substantial promise for improving the reproducibility and reliability of nanoparticle genotoxicity studies. PMID- 22047054 TI - A novel class of small molecule inhibitors of HDAC6. AB - Histone deacetylases (HDACs) are a family of enzymes that play significant roles in numerous biological processes and diseases. HDACs are best known for their repressive influence on gene transcription through histone deacetylation. Mapping of nonhistone acetylated proteins and acetylation-modifying enzymes involved in various cellular pathways has shown protein acetylation/deacetylation also plays key roles in a variety of cellular processes including RNA splicing, nuclear transport, and cytoskeletal remodeling. Studies of HDACs have accelerated due to the availability of small molecule HDAC inhibitors, most of which contain a canonical hydroxamic acid or benzamide that chelates the metal catalytic site. To increase the pool of unique and novel HDAC inhibitor pharmacophores, a pharmacological active compound screen was performed. Several unique HDAC inhibitor pharmacophores were identified in vitro. One class of novel HDAC inhibitors, with a central naphthoquinone structure, displayed a selective inhibition profile against HDAC6. Here we present the results of a unique class of HDAC6 inhibitors identified using this compound library screen. In addition, we demonstrated that treatment of human acute myeloid leukemia cell line MV4-11 with the selective HDAC6 inhibitors decreases levels of mutant FLT-3 and constitutively active STAT5 and attenuates Erk phosphorylation, all of which are associated with the inhibitor's selective toxicity against leukemia. PMID- 22047055 TI - Inhibition of development of Shiga toxin-converting bacteriophages by either treatment with citrate or amino acid starvation. AB - OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) are pathogenic strains, whose virulence depends on induction of Shiga toxin-converting prophages and their subsequent lytic development. We explored which factors or conditions could inhibit development of these phages, potentially decreasing virulence of STEC. MATERIALS AND METHODS: Lytic development of Shiga toxin-converting bacteriophages was monitored after mitomycin C-provoked prophage induction under various conditions. Phage DNA replication efficiency was assessed by measurement of DNA amount in cells using quantitative polymerase chain reaction. RESULTS: We demonstrated that the use of citrate delayed Shiga toxin-converting phage development after prophage induction. This effect was independent on efficiency of prophage induction and phage DNA replication. However, an excess of glucose reversed the effect of citrate. Amino acid starvation prevented the phage development in bacteria both able and unable to induce the stringent response. CONCLUSIONS: Lytic development of Shiga toxin-converting bacteriophages can be inhibited by either the presence of citrate or amino acid starvation. We suggest that the inhibition caused by the latter condition may be due to a block in prophage induction or phage DNA replication or both. APPLICATIONS: Our findings may facilitate development of procedures for treatment of STEC-infected patients. PMID- 22047056 TI - Evaluation of a multiplex real-time polymerase chain reaction for the quantification of Escherichia coli O157 in cattle feces. AB - Cattle are asymptomatic reservoirs for Escherichia coli O157, a major foodborne pathogen. The organism generally colonizes the hindgut of cattle and is shed in the feces at low concentrations. The objective of this research was to evaluate a multiplex, real-time polymerase chain reaction (mqPCR) assay for quantification of E. coli O157 in cattle feces using stx1, stx2, and rfbE gene targets. Primer efficiency and analytical sensitivity of the assay were evaluated with a single or pooled (five strain) culture of E. coli O157. In pure culture, the minimum detection limit of the assay was 1.4*10(3) CFU/mL and 3.6*10(3) CFU/mL for the single and five-strain mixture of E. coli O157, respectively. Diagnostic sensitivity was analyzed using DNA extracted from cattle feces spiked with E. coli O157. In feces spiked with the pooled mixture of five E. coli O157 strains, the minimum detection limit was 3.6*10(4) CFU/g. We also evaluated the assay with feces from cattle experimentally inoculated with E. coli O157 by comparing the results to a culture-based method. For the majority of samples tested, the concentration of E. coli O157 detected by the real-time and culture methods was within one log difference. However, the assay could only be evaluated for cattle shedding high concentrations of E. coli O157. In conclusion, the mqPCR quantifying E. coli O157 in cattle feces using stx1, stx2, and rfbE gene targets may have use in detecting and quantifying super shedders, but is not applicable for quantification in animals shedding low concentrations (10(2) to 10(3) CFU/g feces). PMID- 22047057 TI - A regional Salmonella enterica serovar Typhimurium outbreak associated with raw beef products, The Netherlands, 2010. AB - Between April and May 2010, several medical microbiological laboratories in the Netherlands notified a total of 90 cases of Salmonella enterica serovar Typhimurium with the same antibiogram type (resistant for ampicillin, tetracycline, and co-trimoxazol) and the same multiple locus variable number tandem repeats analysis pattern (03-16-09-NA-311) or single locus variants. Date of illness onset ranged from end of March to mid-May with a peak in the second week of April. Almost half of the cases were hospitalized. Cases completed a questionnaire about food items and other risk factors in the 7 days before illness onset. A matched case-control study was performed. Consumption of "ossenworst" (matched odds ratio 48.2 [95% confidence interval (CI): 3.9-595.9]) and filet americain (8.5 [95% CI: 1.0-73.6]) were found to be significant risk factors for illness. Eighty percent of the cases had eaten at least one or both raw meat products. The producer of the ground beef that was used to produce the "ossenworst" was identified, but no microbiological evidence was found. Consumers should be made more aware of the presence of raw meat in ready-to-eat products and of the potential risk in eating these products. Vulnerable persons such as young children, elderly, and persons with poor health should be discouraged from eating these products. Detection of this outbreak was mainly based on the antibiogram pattern that had identified possible cases 10 days before detailed typing results from the reference laboratory became available, thus facilitating early case findings. PMID- 22047058 TI - An emerging role for the nuclear localization of maspin in the suppression of tumor progression and metastasis. AB - Maspin, a member of the serpin family of serine protease inhibitors, was originally identified as a tumor suppressor that is expressed in normal mammary epithelial cells but is reduced or absent in breast carcinomas. Early enthusiasm for maspin as a biomarker for disease progression has been tempered by clinical data that associates maspin with favourable outcomes in some studies and poor prognosis in others. Here, we review all of the published clinical studies for maspin in breast and ovarian cancers and propose that the apparent discordance between clinical reports is a consequence of differential cellular distribution of maspin. Indeed, it was thought that an extracellular pool of maspin possessed tumor suppressor activity, acting by inhibiting migration and increasing cell adhesion. Recent evidence from our group and others indicates, however, that the nuclear localization of maspin in cancer cells is necessary for its tumor suppressor activity. We provide additional data here to demonstrate that nuclear localized maspin binds to chromatin and is required to effectively prevent cells from metastasizing. Our knowledge of other serpins that localize to the nucleus should help to inform future studies of nuclear maspin. Elucidation of the molecular mechanisms regulating the localization and activities of maspin should pave the way for the development of improved diagnostics and therapies for cancer. PMID- 22047059 TI - Cognitive effects of chemotherapy-induced menopause in breast cancer. AB - This study examined whether chemotherapy-induced menopause affects cognitive functioning in women with early breast cancer. The neuropsychological performance of 121 breast cancer patients (age M=49.62, SD=8.11, range=25.25-67.92) treated with chemotherapy was assessed pre-chemotherapy, as well as 1, 6, and 18 months post-chemotherapy completion. Linear mixed modeling was used to evaluate the data. Type of menopause (pre, chemotherapy-induced, and post menopause) was found to significantly interact with cognitive performance on two cognitive variables. Specifically, chemotherapy-induced menopausal women did not show any significant changes in performance on an abstract reasoning task, while the pre-menopausal and post-menopausal groups significantly improved over time. A significant interaction on a test of finger dexterity and coordination was also found, although inspection of the results indicated that this was due to a significant improvement in the pre-menopausal groups at 6 months post chemotherapy. After chemotherapy most cognitive variables showed improvements over time, although two indicators of verbal memory showed significant declines immediately after chemotherapy, with improvement by 18 months post completion. The current study found little evidence to suggest that chemotherapy-induced menopause broadly affects cognitive functioning after treatment administration. However, longer follow-up assessments are warranted to assess the long-term effects of combined chemotherapy and endocrine treatment. PMID- 22047060 TI - Quality assessment of the registration of vulvar and vaginal premalignant lesions at the Cancer Registry of Norway. AB - BACKGROUND: A crucial factor concerning the utility of Cancer Registries is the data quality with respect to comparability, completeness, validity and timeliness. However, the data quality of the registration of premalignant lesions has rarely been addressed. High grade vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VaIN) are premalignant lesions which may develop into cancer, and are often associated with infection with the human papillomarvirus (HPV). The aim was to evaluate the quality of registration of VIN and VaIN at the Cancer Registry of Norway (CRN). MATERIAL AND METHODS: We re collected all notifications with high grade VIN and VaIN diagnoses during 2002 to 2007 from pathology laboratories, and compared these to the data in the CRN database so as to quantitatively measure the completeness, validity and timeliness of the data. RESULTS: Over the period 2002 to 2007 we estimated the completeness of the 1556 VIN and 297 VaIN notifications to be 95.0% and 92.9%, respectively. The original and reabstracted topography codes showed major discrepancies for 12 of 642 (1.9%) VIN and 7 of 128 (5.5%) VaIN notifications. The original and reabstracted morphology codes for VIN and VaIN were identical for 724 out of 814 notifications. Sixteen notifications had a major discrepancy. For the period 2002 to 2007 the median time elapsed between date of diagnosis and date of registration were 436 and 441 days for VIN and VaIN cases, respectively. DISCUSSION: Based on the present analysis of the comparability, completeness, validity and timeliness of premalignant lesions of vulva and vagina, we conclude that the Cancer Registry of Norway is able to monitor such premalignant lesions satisfactorily. PMID- 22047061 TI - Initial recombination in the track of heavy charged particles: numerical solution for air filled ionization chambers. AB - INTRODUCTION: Modern particle therapy facilities enable sub-millimeter precision in dose deposition. Here, also ionization chambers (ICs) are used, which requires knowledge of the recombination effects. Up to now, recombination is corrected using phenomenological approaches for practical reasons. In this study the effect of the underlying dose distribution on columnar recombination, a quantitative model for initial recombination, is investigated. MATERIAL AND METHODS: Jaffe's theory, formulated in 1913 quantifies initial recombination by elemental processes, providing an analytical (closed) solution. Here, we investigate the effect of the underlying charged carrier distribution around a carbon ion track. The fundamental partial differential equation, formulated by Jaffe, is solved numerically taking into account more realistic charge carrier distributions by the use of a computer program (Gascoigne 3D). The investigated charge carrier distributions are based on track structure models, which follow a 1/r(2) behavior at larger radii and show a constant value at small radii. The results of the calculations are compared to the initial formulation and to data obtained in experiments using carbon ion beams. RESULTS: The comparison between the experimental data and the calculations shows that the initial approach made by Jaffe is able to reproduce the effects of initial recombination. The amorphous track structure based charge carrier distribution does not reproduce the experimental data well. A small additional correction in the assessment of the saturation current or charge is suggested by the data. CONCLUSION: The established model of columnar recombination reproduces the experimental data well, whereas the extensions using track structure models do not show such an agreement. Additionally, the effect of initial recombination on the saturation curve (i.e. Jaffe plot) does not follow a linear behavior as suggested by current dosimetry protocols, therefore higher order corrections (such as the investigated ones) might be necessary. PMID- 22047062 TI - D2-symmetric dirhodium catalyst derived from a 1,2,2 triarylcyclopropanecarboxylate ligand: design, synthesis and application. AB - Dirhodium tetrakis-(R)-(1-(4-bromophenyl)-2,2-diphenylcyclopropanecarboxylate) (Rh(2)(R-BTPCP)(4)) was found to be an effective chiral catalyst for enantioselective reactions of aryl- and styryldiazoacetates. Highly enantioselective cyclopropanations, tandem cyclopropanation/Cope rearrangements and a combined C-H functionalization/Cope rearrangement were achieved using Rh(2)(R-BTPCP)(4) as catalyst. The advantages of Rh(2)(R-BTPCP)(4) include its ease of synthesis, its tolerance to the size of the ester group in the styryldiazoacetates, and its compatibility with dichloromethane as solvent. Computational studies suggest that the catalyst adopts a D(2)-symmetric arrangement, but when the carbenoid binds to the catalyst, two of the p bromophenyl groups on the ligands rotate outward to make room for the carbenoid and the approach of the substrate to the carbenoid. PMID- 22047066 TI - Enhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles. AB - As 95% of all prescriptions are for orally administered drugs, the issue of oral absorption is central to the development of pharmaceuticals. Oral absorption is limited by a high molecular weight (>500 Da), a high log P value (>2.0) and low gastrointestinal permeability. We have designed a triple action nanomedicine from a chitosan amphiphile: quaternary ammonium palmitoyl glycol chitosan (GCPQ), which significantly enhances the oral absorption of hydrophobic drugs (e.g., griseofulvin and cyclosporin A) and, to a lesser extent, the absorption of hydrophilic drugs (e.g., ranitidine). The griseofulvin and cyclosporin A C(max) was increased 6- and 5-fold respectively with this new nanomedicine. Hydrophobic drug absorption is facilitated by the nanomedicine: (a) increasing the dissolution rate of hydrophobic molecules, (b) adhering to and penetrating the mucus layer and thus enabling intimate contact between the drug and the gastrointestinal epithelium absorptive cells, and (c) enhancing the transcellular transport of hydrophobic compounds. Although the C(max) of ranitidine was enhanced by 80% with the nanomedicine, there was no appreciable opening of tight junctions by the polymer particles. PMID- 22047067 TI - Childhood chronic anterior uveitis associated with vernal keratoconjunctivitis (VKC): successful treatment with topical tacrolimus. Case series. AB - Uveitis treatment involves topical corticosteroids along with cycloplegic mydriatics. Particularly severe cases may require systemic corticosteroids and immunosuppressive drugs. Vernal keratoconjunctivitis (VKC) treatment consists of a brief period of topical corticosteroids and/or cyclosporine. In patients refractory to traditional treatment, the use of 0.1% topical ophtalmic FK- 506 (tacrolimus) ointment has been occasionally reported.This is the first report of the coexistence of uveitis and VKC. The documented response to topical tacrolimus eyedrop of uveitis and VKC is also of interest, in particular since to our knowledge there are no published reports on its clinical use in uveitis. PMID- 22047068 TI - Catalytic enantioselective intermolecular cycloaddition of diazodiketoester derived carbonyl ylides with indoles using chiral dirhodium(II) carboxylates. AB - The first example of enantioselective intermolecular cycloaddition of carbonyl ylides with indoles is described. The cycloaddition of five- and six-membered carbonyl ylides derived from diazodiketoesters with N-methylindoles under catalysis by dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], Rh(2)(S-TCPTTL)(4), gave cycloadducts in high yields and with high levels of enantioselectivity (up to 99% ee) as well as excellent exo diastereoselectivity. PMID- 22047069 TI - Retargeted clostridial neurotoxins as novel agents for treating chronic diseases. AB - Botulinum neurotoxin (BoNT) A and B are used to treat neuropathic disorders; if retargeted, these agents could be used to treat medical conditions that involve secretion from nonneuronal cells. Here, we report novel strategies for successfully retargeting BoNTs, and also tetanus neurotoxin (TeNT), to primary human blood monocyte-derived macrophages where BoNT/B inhibited the release of tumor necrosis factor-alpha, a cytokine that plays a key role in inflammation. Furthermore, mice treated with retargeted BoNT/B exhibited a significant reduction in macrophage (MPhi) recruitment, indicating that these toxins can be used to treat chronic inflammation. PMID- 22047071 TI - A randomised controlled crossover trial evaluating Television Assisted Prompting (TAP) for adults with acquired brain injury. AB - Assistive technologies for cognition (ATC) provide an effective means to compensate for prospective memory failures among adults with acquired brain injury (ABI; de Joode, van Heugten, Verhey, & van Boxtel, 2010 ; Sohlberg et al., 2007 ). This study evaluated a novel ATC device, the Television Assisted Prompting (TAP) system, which provides audiovisual reminders at scheduled prospective times on a person's home television. A randomised, controlled crossover design evaluated task completion for two preferred, two non-preferred, and two structured experimental tasks among 23 adults with ABI between two conditions: TAP prompting or typical (TYP) practice, without TAP reminders. Main outcomes showed a significant advantage of prospective memory prompting (72% completion) over no prompting (43% completion) and higher task completion with TAP prompting for researcher-assigned experimental tasks (81%) compared to self selected preferred (68%) or non-preferred (68%) tasks. Results are discussed in the context of ATC efficacy to support prospective memory prompting following ABI, with contributions and future directions for continued investigation of customisation of prompts to maximise task completion. PMID- 22047072 TI - Statement of retraction. An evaluation of the association of malnutrition with nosocomial infections in elderly patients. PMID- 22047073 TI - Effects of Erxian decoction, a Chinese medicinal formulation, on serum lipid profile in a rat model of menopause. AB - BACKGROUND: The prevalence and risk of cardiovascular disease increase after menopause in correlation with the progression of abnormality in the serum lipid profile and the deprivation of estrogen. Erxian decoction (EXD), a Chinese medicinal formulation for treating menopausal syndrome, stimulates ovarian estrogen biosynthesis. This study investigates whether EXD improves the serum lipid profile in a menopausal rat model. METHODS: Twenty-month-old female Sprague Dawley rats were treated with EXD and its constituent fractions. Premarin was administered for comparison. After eight weeks of treatment, rats were sacrificed and the serum levels of total cholesterol, triglyceride, high-density-lipoprotein cholesterol and low-density-lipoprotein cholesterol were determined. The hepatic protein levels of 3-hydroxy-3-methyl-glutaryl-CoA reductase and low-density lipoprotein receptor were assessed with Western blot. RESULTS: The serum levels of total cholesterol and low-density-lipoprotein cholesterol were significantly lower in the EXD-treated group than in the constituent fractions of EXD or premarin groups. However, the serum levels of triglyceride and high-density lipoprotein cholesterol were not significantly different from the control groups. Results from Western blot suggest that EXD significantly down-regulated the protein level of 3-hydroxy-3-methyl-glutaryl-CoA reductase and up-regulated low density-lipoprotein receptor. Conclusion EXD improves serum lipid profile in a menopausal rat model through the suppression of the serum levels of total cholesterol and low-density-lipoprotein cholesterol, possibly through the down regulation of the 3-hydroxy-3-methyl-glutaryl-CoA and up-regulation of the low density-lipoprotein receptor. PMID- 22047074 TI - Glycoside cleavage by a new mechanism in unsaturated glucuronyl hydrolases. AB - Unsaturated glucuronyl hydrolases (UGLs) from GH family 88 of the CAZy classification system cleave a terminal unsaturated sugar from the oligosaccharide products released by extracellular bacterial polysaccharide lyases. This pathway, which is involved in extracellular bacterial infection, has no equivalent in mammals. A novel mechanism for UGL has previously been proposed in which the enzyme catalyzes hydration of a vinyl ether group in the substrate, with subsequent rearrangements resulting in glycosidic bond cleavage. However, clear evidence for this mechanism has been lacking. In this study, analysis of the products of UGL-catalyzed reactions in water, deuterium oxide, and dilute methanol in water, in conjunction with the demonstration that UGL rapidly cleaves thioglycosides and glycosides of inverted anomeric configuration (substrates that are resistant to hydrolysis by classical glycosidases), provides strong support for this new mechanism. A hydration-initiated process is further supported by the observed UGL-catalyzed hydration of a C-glycoside substrate analogue. Finally, the observation of a small beta-secondary kinetic isotope effect suggests a transition state with oxocarbenium ion character, in which the hydrogen at carbon 4 adopts an axial geometry. Taken together, these observations validate the novel vinyl ether hydration mechanism and are inconsistent with either inverting or retaining direct hydrolase mechanisms at carbon 1. PMID- 22047075 TI - SWI/SNF regulates the alternative processing of a specific subset of pre-mRNAs in Drosophila melanogaster. AB - BACKGROUND: The SWI/SNF chromatin remodeling factors have the ability to remodel nucleosomes and play essential roles in key developmental processes. SWI/SNF complexes contain one subunit with ATPase activity, which in Drosophila melanogaster is called Brahma (Brm). The regulatory activities of SWI/SNF have been attributed to its influence on chromatin structure and transcription regulation, but recent observations have revealed that the levels of Brm affect the relative abundances of transcripts that are formed by alternative splicing and/or polyadenylation of the same pre-mRNA. RESULTS: We have investigated whether the function of Brm in pre-mRNA processing in Drosophila melanogaster is mediated by Brm alone or by the SWI/SNF complex. We have analyzed the effects of depleting individual SWI/SNF subunits on pre-mRNA processing throughout the genome, and we have identified a subset of transcripts that are affected by depletion of the SWI/SNF core subunits Brm, Snr1 or Mor. The fact that depletion of different subunits targets a subset of common transcripts suggests that the SWI/SNF complex is responsible for the effects observed on pre-mRNA processing when knocking down Brm. We have also depleted Brm in larvae and we have shown that the levels of SWI/SNF affect the pre-mRNA processing outcome in vivo. CONCLUSIONS: We have shown that SWI/SNF can modulate alternative pre-mRNA processing, not only in cultured cells but also in vivo. The effect is restricted to and specific for a subset of transcripts. Our results provide novel insights into the mechanisms by which SWI/SNF regulates transcript diversity and proteomic diversity in higher eukaryotes. PMID- 22047076 TI - Development of methods for studying the differentiation of human mesenchymal stem cells under cyclic compressive strain. AB - Human mesenchymal stem cells (hMSC) have numerous potential advantages over terminally differentiated cells and embryonic stem cells for use in tissue engineering applications. The aims of this study were to develop methods to test the hypothesis that hMSC could be differentiated using cyclic compressive strain alone. hMSC were successfully isolated, purified using D7-FIB antibody, cloned, and characterized. The cells were subsequently analyzed using fluorescence activated cell sorting using a panel of antibodies and differentiation into multiple cell lineages. D7FIB-positive cells were then seeded into collagen alginate scaffolds and subjected to 10% or 15% cyclic compressive strain for 4 out of 24 hours for up to 21 days in a bespoke servo-assisted displacement controlled device. Cells were analyzed using adenosine triphosphate assay to determine cell number, live-dead cell assay, and quantitative real-time polymerase chain reaction at 7 and 21 days. Cloned D7-FIB-positive hMSCs showed evidence of differentiation to an osteogenic lineage under 10% cyclic compressive strain alone (core binding factor alpha 1 (CBFA-1) was significantly upregulated at 7 and 21 days by a factor of 18.3 and 32.2, respectively) and to an osteo chondrogenic lineage under 15% cyclic compressive strain alone (increased expression of CBFA-1, Sox9, and aggrecan). A combination of a composite viscoelastic scaffold and controlled cyclic compressive strain may be useful for study of the differentiation of MSC. PMID- 22047077 TI - Targeting the assembly of bacterial cell division protein FtsZ with small molecules. AB - FtsZ is the key protein of bacterial cell division and an emergent target for new antibiotics. It is a filament-forming GTPase and a structural homologue of eukaryotic tubulin. A number of FtsZ-interacting compounds have been reported, some of which have powerful antibacterial activity. Here we review recent advances and new approaches in modulating FtsZ assembly with small molecules. This includes analyzing their chemical features, binding sites, mechanisms of action, the methods employed, and computational insights, aimed at a better understanding of their molecular recognition by FtsZ and at rational antibiotic design. PMID- 22047079 TI - A comparative analysis of MC4R gene sequence, polymorphism, and chromosomal localization in Chinese raccoon dog and Arctic fox. AB - Numerous mutations of the human melanocortin receptor type 4 (MC4R) gene are responsible for monogenic obesity, and some of them appear to be associated with predisposition or resistance to polygenic obesity. Thus, this gene is considered a functional candidate for fat tissue accumulation and body weight in domestic mammals. The aim of the study was comparative analysis of chromosome localization, nucleotide sequence, and polymorphism of the MC4R gene in two farmed species of the Canidae family, namely the Chinese raccoon dog (Nycterutes procyonoides procyonoides) and the arctic fox (Alopex lagopus). The whole coding sequence, including fragments of 3'UTR and 5'UTR, shows 89% similarity between the arctic fox (1276 bp) and Chinese raccoon dog (1213 bp). Altogether, 30 farmed Chinese raccoon dogs and 30 farmed arctic foxes were searched for polymorphisms. In the Chinese raccoon dog, only one silent substitution in the coding sequence was identified; whereas in the arctic fox, four InDels and two single-nucleotide polymorphisms (SNPs) in the 5'UTR and six silent SNPs in the exon were found. The studied gene was mapped by FISH to the Chinese raccoon dog chromosome 9 (NPP9q1.2) and arctic fox chromosome 24 (ALA24q1.2-1.3). The obtained results are discussed in terms of genome evolution of species belonging to the family Canidae and their potential use in animal breeding. PMID- 22047078 TI - Structural and evolutionary divergence of eukaryotic protein kinases in Apicomplexa. AB - BACKGROUND: The Apicomplexa constitute an evolutionarily divergent phylum of protozoan pathogens responsible for widespread parasitic diseases such as malaria and toxoplasmosis. Many cellular functions in these medically important organisms are controlled by protein kinases, which have emerged as promising drug targets for parasitic diseases. However, an incomplete understanding of how apicomplexan kinases structurally and mechanistically differ from their host counterparts has hindered drug development efforts to target parasite kinases. RESULTS: We used the wealth of sequence data recently made available for 15 apicomplexan species to identify the kinome of each species and quantify the evolutionary constraints imposed on each family of apicomplexan kinases. Our analysis revealed lineage specific adaptations in selected families, namely cyclin-dependent kinase (CDK), calcium-dependent protein kinase (CDPK) and CLK/LAMMER, which have been identified as important in the pathogenesis of these organisms. Bayesian analysis of selective constraints imposed on these families identified the sequence and structural features that most distinguish apicomplexan protein kinases from their homologs in model organisms and other eukaryotes. In particular, in a subfamily of CDKs orthologous to Plasmodium falciparum crk-5, the activation loop contains a novel PTxC motif which is absent from all CDKs outside Apicomplexa. Our analysis also suggests a convergent mode of regulation in a subset of apicomplexan CDPKs and mammalian MAPKs involving a commonly conserved arginine in the alphaC helix. In all recognized apicomplexan CLKs, we find a set of co conserved residues involved in substrate recognition and docking that are distinct from metazoan CLKs. CONCLUSIONS: We pinpoint key conserved residues that can be predicted to mediate functional differences from eukaryotic homologs in three identified kinase families. We discuss the structural, functional and evolutionary implications of these lineage-specific variations and propose specific hypotheses for experimental investigation. The apicomplexan-specific kinase features reported in this study can be used in the design of selective kinase inhibitors. PMID- 22047080 TI - MMP7 -181G allele is a low-penetrant risk factor for cancer development in East Asians. AB - Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificity. Its expression is associated with tumor invasion, metastasis, and survival for a number of cancers. However, data from published studies with individually low statistical power are conflicting. Here, we performed a meta-analysis of 14 publications (16 case-control studies) to better assess the purported relationship. Eligible studies were identified by searching the Pubmed database. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Overall, we found that the -181 G allele increased cancer risk in East Asians (G-allele vs. A-allele, OR=1.35, 95% CI: 1.25-1.46, P(heterogeneity)=0.01; GA vs. AA, OR=1.40, 95% CI: 1.16-1.69, P(heterogeneity)=0.04; GG+GA vs. AA, OR=1.52, 95% CI: 1.30-1.78, P(heterogeneity)=0.00). Similarly, in the stratified analysis by cancer type and source of control, significantly increased cancer risk was indicated. Our study showed evidence that MMP7 -181A/G polymorphism may increase cancer risk in the East Asian population. Future studies with larger sample size are warranted to further evaluate this association in greater detail. PMID- 22047081 TI - Analysis of p53 tumor suppressor pathway genes in chronic lymphocytic leukemia. AB - The p53 tumor suppressor gene plays an important role in preventing tumor development. The p53 protein interacts with other p53 signal pathway members to control cell proliferation. In this study, expression of the p53, Human homolog of murine Double Minute 2 (HDM2), p14Alternating Reading Frame (ARF), Zinc Finger and BTB domain containing 7A (ZBTB7A), and B-Cell Lymphoma 6 (BCL6) genes was quantitatively investigated by real-time polymerase chain reaction (PCR) in the peripheral blood of patients with chronic lymphocytic leukemia (CLL) and healthy controls. Plasma fibronectin levels were determined by enzyme-linked immunosorbent assay. Expression of the p53, p14, and HDM2 genes were significantly higher in the patients. However, ZBTB7A and BCL6 gene expression was not detectable in both groups. A positive correlation between p14ARF and HDM2 expression and a negative correlation between p53 and p14ARF expression was observed. Expression of the p14ARF and HDM2 genes were inversely correlated in the control group. Neither HDM2 nor p14ARF gene expression was correlated with p53 expression. The p53 gene was also analyzed for the presence of mutations. A splice-site mutation was found in a single patient. Our findings indicate that expression of the p53, p14ARF, and HDM2 genes are associated with CLL. Elucidation of the mutual interactions at the protein level warrants further studies. PMID- 22047083 TI - Regioselective synthesis and slow-release Suzuki-Miyaura cross-coupling of MIDA boronate-functionalized isoxazoles and triazoles. AB - The efficient preparation of heterocycles with a range of substitutions ortho to heteroatoms remains as a challenge in organic synthesis, particularly relevant to the construction of druglike molecules due to the ubiquitous presence of such moieties in that chemical space. Modular installation of heterocyclic building blocks using Suzuki-Miyaura cross-coupling is a conceptually useful strategy to address this challenge, though this has historically been met with technical difficulty due to issues of inaccessibility and instability of the requisite heterocyclic boronates. Herein we report a mild and highly regioselective cycloaddition approach which affords convenient access to stable MIDA boronate functionalized isoxazoles and triazoles and their subsequent efficient Suzuki Miyaura cross-coupling. This methodology is then further applied to a set of druglike compounds in an efficient one-pot telescoped sequence in line with green chemistry principles. PMID- 22047082 TI - EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 as potential prognostic markers for postoperative Taiwanese colorectal cancer patients. AB - Undetected micrometastasis may play a key role in the early relapse of colorectal cancer (CRC) patients. The aim of this study was to detect circulating tumor cells (CTCs) for predicting early relapse of CRC patients by a weighted enzymatic chip array (WEnCA) and analyze 15 candidate genes associated with CRC carcinogenesis. The genes of 105 postoperative CRC patients were analyzed by membrane array and direct sequencing. We constructed a WEnCA platform including five prognosis-related genes and analyzed the detection rate of WEnCA for CTCs in 30 clinically confirmed CRC relapse patients. Postoperative relapse was significantly correlated with gene overexpression, including EVI2B (p=0.001, OR=4.622), ATP2A2 (p=0.006, OR=4.688), S100B (p=0.001, OR=11.521), TM4SF3 (p=0.001, OR=6.756), and OLFM4 (p=0.008, OR=3.545). Using WEnCA (weighting score of each gene: 5 to EVI2B, 5 to ATP2A2, 12 to S100B, 7 to TM4SF3, and 4 to OLFM4), we could detect CTCs presenting these genotypes in relapsed CRC patients. The sensitivity, specificity, and accuracy were 94.7%, 93.5%, and 97%, respectively. The results of the present study suggest that EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 could be potential prognostic markers for CRC patients. PMID- 22047084 TI - Generation of recombinant single-chain antibodies neutralizing the cytolytic activity of vaginolysin, the main virulence factor of Gardnerella vaginalis. AB - BACKGROUND: Gardnerella vaginalis is identified as the predominant colonist of the vaginal tract in women with bacterial vaginosis. Vaginolysin (VLY) is a protein toxin released by G. vaginalis. VLY possesses cytolytic activity and is considered as a main virulence factor of G. vaginalis. Inhibition of VLY-mediated cell lysis by antibodies may have important physiological relevance. RESULTS: Single-chain variable fragments of immunoglobulins (scFvs) were cloned from two hybridoma cell lines producing neutralizing antibodies against VLY and expressed as active proteins in E. coli. For each hybridoma, two variants of anti-VLY scFv consisting of either VL-VH or VH-VL linked with a 20 aa-long linker sequence (G4S)4 were constructed. Recovery of scFvs from inclusion bodies with subsequent purification by metal-chelate chromatography resulted in VLY-binding proteins that were predominantly monomeric. The antigen-binding activity of purified scFvs was verified by an indirect ELISA. The neutralizing activity was investigated by in vitro hemolytic assay and cytolytic assay using HeLa cell line. Calculated apparent Kd values and neutralizing potency of scFvs were in agreement with those of parental full-length antibodies. VH-VL and VL-VH variants of scFvs showed similar affinity and neutralizing potency. The anti-VLY scFvs derived from hybridoma clone 9B4 exhibited high VLY-neutralizing activity both on human erythrocytes and cervical epithelial HeLa cells. CONCLUSIONS: Hybridoma-derived scFvs with VLY-binding activity were expressed in E. coli. Recombinant anti-VLY scFvs inhibited VLY-mediated cell lysis. The monovalent scFvs showed reduced affinity and neutralizing potency as compared to the respective full-length antibodies. The loss of avidity could be restored by generating scFv constructs with multivalent binding properties. Generated scFvs is the first example of recombinant single-chain antibodies with VLY-neutralizing activity produced in prokaryote expression system. G. vaginalis caused infections continue to be a world-wide problem, therefore neutralizing recombinant antibodies may provide novel therapeutic agents useful in the treatment of bacterial vaginosis and other diseases caused by G. vaginalis. PMID- 22047085 TI - Oxidative stress-induced modifications of histidyl-tRNA synthetase affect its tRNA aminoacylation activity but not its immunoreactivity. AB - The aminoacyl-tRNA synthetases are ubiquitously expressed enzymes that catalyze the esterification of amino acids to their cognate tRNAs. Autoantibodies against several aminoacyl-tRNA synthetases are found in autoimmune polymyositis and dermatomyositis patients. Because necrosis is often found in skeletal muscle biopsies of these patients, we hypothesized that cell-death-induced protein modifications may help in breaking immunological tolerance. Since cell death is associated with oxidative stress, the effect of oxidative stress on the main myositis-specific autoantibody target Jo-1 (histidyl-tRNA synthetase; HisRS) was studied in detail. The exposure of Jurkat cells to hydrogen peroxide resulted in the detection of several oxidized methionines and one oxidized tryptophan residue in the HisRS protein, as demonstrated by mass spectrometry. Unexpectedly, the tRNA aminoacylation activity of HisRS appeared to be increased upon oxidative modification. The analysis of myositis patient sera did not lead to the detection of autoantibodies that are specifically reactive with the modified HisRS protein. The results of this study demonstrate that the Jo-1/HisRS autoantigen is modified under oxidative stress conditions. The consequences of these modifications for the function of HisRS and its autoantigenicity are discussed. PMID- 22047087 TI - IVth International Symposium of Veterinary Laboratory Diagnosticians (report). PMID- 22047086 TI - A prospective study of vaginal trichomoniasis and HIV-1 shedding in women on antiretroviral therapy. AB - BACKGROUND: Trichomonas vaginalis has been associated with increased vaginal HIV 1 RNA shedding in antiretroviral therapy (ART)-naive women. The effect of trichomoniasis on vaginal HIV-1 shedding in ART-treated women has not been characterized. We tested the hypothesis that T. vaginalis infection would increase vaginal HIV-1 RNA shedding in women on ART, and that successful treatment would reduce vaginal HIV-1 RNA levels. METHODS: We conducted a prospective cohort study including monthly follow-up of 147 women receiving ART in Mombasa, Kenya. Those with T. vaginalis infection, defined by the presence of motile trichomonads on vaginal saline wet mount, received treatment with single dose metronidazole (2 g). Test of cure was performed at the next monthly visit. Using the pre-infection visit as the reference category, we compared detection of vaginal HIV-1 RNA before versus during and after infection using generalized estimating equations. A cut-off of 100 HIV-1 RNA copies/swab was used as the lower limit for linear quantitation. RESULTS: Among 31 women treated for trichomoniasis, the concentration of vaginal HIV-1 RNA was above the limit for quantitation before, during, and after T. vaginalis infection in 4 (13% [95% CI 4% - 30%]), 4 (13% [95% CI 4% - 30%]), and 5 (16% [95% confidence interval {CI} 5% - 34%]) women respectively. After adjusting for potential confounding factors, we could detect no difference in the likelihood of detecting vaginal HIV-1 RNA before versus during infection (odds ratio [OR] 1.41, 95% CI 0.23 - 8.79, p = 0.7). In addition, detection of HIV-1 RNA was similar before infection versus after successful treatment (OR 0.68, 95% CI (0.13 - 3.45), p = 0.6). CONCLUSION: Detection of vaginal HIV-1 RNA during ART was uncommon at visits before, during and after T. vaginalis infection. PMID- 22047089 TI - Assessment of the knowledge of graphical symbols labelled on malaria rapid diagnostic tests in four international settings. AB - BACKGROUND: Graphical symbols on in vitro diagnostics (IVD symbols) replace the need for text in different languages and are used on malaria rapid diagnostic tests (RDTs) marketed worldwide. The present study assessed the comprehension of IVD symbols labelled on malaria RDT kits among laboratory staff in four different countries. METHODS: Participants (n = 293) in Belgium (n = 96), the Democratic Republic of the Congo (DRC, n = 87), Cambodia (n = 59) and Cuba (n = 51) were presented with an anonymous questionnaire with IVD symbols extracted from ISO 15223 and EN 980 presented as stand-alone symbols (n = 18) and in context (affixed on RDT packages, n = 16). Responses were open-ended and scored for correctness by local professionals. RESULTS: Presented as stand-alone, three and five IVD symbols were correctly scored for comprehension by 67% and 50% of participants; when contextually presented, five and seven symbols reached the 67% and 50% correct score respectively. 'Batch code' scored best (correctly scored by 71.3% of participants when presented as stand-alone), 'Authorized representative in the European Community' scored worst (1.4% correct). Another six IVD symbols were scored correctly by less than 10% of participants: 'Do not reuse', 'In vitro diagnostic medical device', 'Sufficient for', 'Date of manufacture', 'Authorised representative in EC', and 'Do not use if package is damaged'. Participants in Belgium and Cuba both scored six symbols above the 67% criterion, participants from DRC and Cambodia scored only two and one symbols above this criterion. Low correct scores were observed for safety-related IVD symbols, such as for 'Biological Risk' (42.7%) and 'Do not reuse' (10.9%). CONCLUSION: Comprehension of IVD symbols on RDTs among laboratory staff in four international settings was unsatisfactory. Administrative and outreach procedures should be undertaken to assure their acquaintance by end-users. PMID- 22047092 TI - Reply to "Comment on 'Electronic structures, vibrational and thermochemical properties of neutral and charged niobium clusters Nb(n), n = 7-12'". PMID- 22047090 TI - Novel pharmacotherapeutic treatments for cocaine addiction. AB - Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine dependence is a public health concern and cause of significant morbidity and mortality worldwide. At present, there are no approved medications for the treatment of this devastating illness, and behavioral interventions have proven to be of limited use. However, there have been a number of recent trials testing promising agents including dopamine agonists, GABAergic medications and the cocaine vaccine. Here we discuss the most recent human clinical trials of potential medications for treatment of cocaine dependence, as well as pre-clinical studies for another promising agent, levo tetrahydropalmatine. Examination of these recent findings shows promise for GABAergic medications and the cocaine vaccine, as well as unique medications such as disulfiram, whose mechanism remains to be determined. Future work may also confirm specific subgroups of patients for treatment response based on clinical characteristics, biomarkers and pharmacogenetics. This review highlights the need for further, bigger studies in order to determine optimal clinical usage. PMID- 22047093 TI - The impact of recombinant fusion-hydrophobin coated surfaces on E. coli and natural mixed culture biofilm formation. AB - The impact of increased surface hydrophobicity on biofilms regarding retardation, repulsion, or attraction was studied with hydrophobin modified glass substrata. Recombinantly produced fungal hydrophobins forming self-assembled monolayers were used as the surface coating. The adsorption dynamics of hydrophobins were analysed with a quartz crystal microbalance which showed the surface coating to be rapid and stable. The change of surface wettability was determined by water contact angle measurements and demonstrated an increase in hydrophobicity in range of 60-62 degrees . The homogeneity of the monolayers was demonstrated by immunofluorescence microscopy. Atomic force microscopy was applied to visualise the uniform texture of the coated materials. The hydrophobin coatings had no impact on different biofilms in terms of spatial distribution, cell numbers, and population composition. In consequence, hydrophobicity might not represent an important parameter for biofilm formation. Nevertheless, recombinant hydrophobins are suitable for large scale surface modification and functionalization with bioactive molecules. PMID- 22047094 TI - A new strategy to investigate the toxicity of nanomaterials using Langmuir monolayers as membrane models. AB - Nanomaterials such as carbon nanotubes (CNTs) and nanoparticles have received enormous attention in analytical areas for their potential applications as new tools for biotechnology and life sciences. Most of these possible applications involve the use of CNTs and related materials as vehicles for drug delivery and/or gene therapy. In this study, we introduce a methodology to evaluate the interactions between CNTs/dendrimers nanoconjugates and phospholipid biomembrane models, using the Langmuir film balance technique. Our main goal was to elucidate the action of engineered nanomaterials in cell membranes, at the molecular level, using a membrane model system. The penetration of single-walled carbon nanotubes (SWCNTs)/polyamidoamine dendrimer nanocomplexes into dipalmitoylphosphatidylcholine monolayers was pronounced, as revealed by adsorption kinetics and surface pressure measurements. These findings suggest that SWCNTs were able to interact even at high surface pressure values, ~30 mN/m. Therefore, the results confirm that the presence of the nanomaterial affects the packing of the synthetic membranes. We believe the methodology introduced here may be of great importance for further nanotoxicity studies. PMID- 22047095 TI - Droplet size scaling of water-in-oil emulsions under turbulent flow. AB - The size of droplets in emulsions is important in many industrial, biological, and environmental systems, as it determines the stability, rheology, and area available in the emulsion for physical or chemical processes that occur at the interface. While the balance of fluid inertia and surface tension in determining droplet size under turbulent mixing in the inertial subrange has been well established, the classical scaling prediction by Shinnar half a century ago of the dependence of droplet size on the viscosity of the continuous phase in the viscous subrange has not been clearly validated in experiment. By employing extremely stable suspensions of highly viscous oils as the continuous phase and using a particle video microscope (PVM) probe and a focused beam reflectance method (FBRM) probe, we report measurements spanning 2 orders of magnitude in the continuous phase viscosity for the size of droplets in water-in-oil emulsions. The wide range in measurements allowed identification of a scaling regime of droplet size proportional to the inverse square root of the viscosity, consistent with the viscous subrange theory of Shinnar. A single curve for droplet size based on the Reynolds and Weber numbers is shown to accurately predict droplet size for a range of shear rates, mixing geometries, interfacial tensions, and viscosities. Viscous subrange control of droplet size is shown to be important for high viscous shear stresses, i.e., very high shear rates, as is desirable or found in many industrial or natural processes, or very high viscosities, as is the case in the present study. PMID- 22047096 TI - Efficient generation of ortho-quinone methide: application to the biomimetic syntheses of (+/-)-schefflone and tocopherol trimers. AB - An efficient method using silver oxide-mediated oxidation for the synthesis of ortho-quinone methides has been developed and applied to the biomimetic syntheses of novel trimeric natural products, (+/-)-schefflone and tocopherol trimers. Further studies of the critical trimerization as well as substrate scope and limitations are also reported. PMID- 22047097 TI - Trends in health-related behavioral risk factors among pregnant women in the United States: 2001-2009. AB - BACKGROUND: Unhealthy lifestyle behaviors during pregnancy often predispose women to multiple risks including adverse pregnancy outcomes and impaired health status for mothers. This study assessed the trends in the prevalence of health-related behavioral risk factors over time among U.S. pregnant women. METHODS: Data from 22,604 pregnant women aged 18-44 years who participated in the 2001-2009 Behavioral Risk Factor Surveillance System were analyzed to assess the trends in the prevalence of behavioral risk factors. Correlates of having individual or clustering healthy behaviors were also assessed among 2295 pregnant women in the 2009 survey. RESULTS: From 2001 to 2009, among pregnant women, the age-adjusted prevalence of engaging in leisure-time exercise and receiving influenza vaccination increased significantly (p<0.05 for linear trends); the prevalence of any alcohol consumption decreased marginally (p=0.065 for linear trend); and the prevalence of binge drinking, smoking, and consuming fruits and vegetables >=5 times/day varied little. Over the 9 years, the percentages of pregnant women who reported having all four healthy behaviors (i.e., not currently smoking, no alcohol consumption, engaging in leisure-time exercise, and receiving influenza vaccination) increased linearly from 7.3% in 2001 to 21.2% in 2009 (p<0.001). Sociodemographic characteristics, perceived health status, and health-care availability were differentially associated with certain individual or clustered healthy behaviors. CONCLUSIONS: Increased efforts emphasizing multiple health related behavioral risk factors including reducing alcohol use, binge drinking, and smoking and improving fruit and vegetable consumption during pregnancy are needed. PMID- 22047098 TI - Obstetric and perinatal outcomes in women with eating disorders. AB - BACKGROUND: We wished to investigate whether women with a history of eating disorders have an increased risk for adverse obstetric and perinatal outcomes. STUDY DESIGN: A retrospective study was conducted comparing pregnancy complications in patients with and without eating disorders. Deliveries occurred during the years 1988-2009 in a tertiary medical center. Women lacking prenatal care and with multiple gestations were excluded from the study. Stratified analyses were performed using multivariable logistic regression models. Odds ratios (OR) and their 95% confidence interval (CI) were computed. A p value<0.05 was considered statistically significant. RESULTS: During the study period, of 117,875 singleton deliveries, 122 (0.1%) occurred in patients with eating disorders. Eating disorders were significantly associated with fertility treatments (5.7% vs. 2.8%, p=0.047), intrauterine growth restriction (7.4% vs. 2.3%, p<0.001), term low birth weight (<2500 g) (7.4% vs. 2.8%, p=0.002), preterm delivery (15.6% vs. 7.5%, p=0.002), and cesarean delivery (25.4% vs. 15.0%, p=0.001). Using multivariable analyses, low birth weight (OR 2.5, 95% CI 1.3 5.0), preterm delivery (OR 2.2, 95% CI 1.4-3.6), and cesarean section (OR 1.9, 95% CI 1.3-2.9) were significantly associated with eating disorders. CONCLUSIONS: Eating disorders are associated with increased risk of adverse pregnancy outcomes. Accordingly, careful surveillance is needed for early detection of possible complications. PMID- 22047099 TI - Perimenopausal vaginal bleeding: diagnostic evaluation and therapeutic options. AB - While significant awareness has been raised about menopause, less attention has been focused on the perimenopausal or "menopausal transition" period. Many women and their physicians remain unaware of the impact of this transitional phase into menopause. Specifically, heavy and unpredictable perimenopausal bleeding is extremely common. It is a normal phenomenon of aging and tends to improve over time. However, about one quarter of perimenopausal women will have heavy flow that persists beyond 3 months and will require medical assistance. The purpose of this review is to focus on the hormonal and physiologic changes that are associated with perimenopausal heavy vaginal bleeding, to present the essential evaluation of causes for this heavy flow, and to outline the evidence for effective medical and surgical treatments. Advances in the understanding of the normal physiology of perimenopause have led to medical therapies that may lead to fewer surgical procedures and hysterectomies and should be of interest to health care practitioners focusing on women's health. Although these issues are addressed in the gynecologic literature, there is relatively less published in other disciplines. PMID- 22047100 TI - Contrasting effects of errorless naming treatment and gestural facilitation for word retrieval in aphasia. AB - We compared the effects of two treatments for aphasic word retrieval impairments, errorless naming treatment (ENT) and gestural facilitation of naming (GES), within the same individuals, anticipating that the use of gesture would enhance the effect of treatment over errorless treatment alone. In addition to picture naming, we evaluated results for other outcome measures that were largely untested in earlier ENT studies. In a single participant crossover treatment design, we examined the effects of ENT and GES in eight individuals with stroke induced aphasia and word retrieval impairments (three semantic anomia, five phonological anomia) in counterbalanced phases across participants. We evaluated effects of the two treatments for a daily picture naming/gesture production probe measure and in standardised aphasia tests and communication rating scales administered across phases of the experiment. Both treatments led to improvements in naming of trained words (small-to-large effect sizes) in individuals with semantic and phonological anomia. Small generalised naming improvements were noted for three individuals with phonological anomia. GES improved use of corresponding gestures for trained words (large effect sizes). Results were largely maintained at one month post-treatment completion. Increases in scores on standardised aphasia testing also occurred for both ENT and GES training. Both ENT and GES led to improvements in naming measures, with no clear difference between treatments. Increased use of gestures following GES provided a potential compensatory means of communication for those who did not improve verbal skills. Both treatments are considered to be effective methods to promote recovery of word retrieval and verbal production skills in individuals with aphasia. PMID- 22047101 TI - Simultaneous determination of mono-, di-, and triglycerides in multiphase systems by online Fourier transform infrared spectroscopy. AB - Glycerides are of significant value for industry as ingredients with different purposes in food or cosmetics. The analysis of glycerides is mainly performed by gas chromatography (GC) or high-pressure liquid chromatography (HPLC), which demonstrate limitations in dealing with multiphase systems. In this article, an in situ differentiation between mono-, di-, and triglycerides in multiphase systems by Fourier transform infrared (FT-IR) spectroscopy is demonstrated. The enzymatic esterification of glycerol with lauric acid was analyzed as a model system. The reaction was carried out in a bubble column reactor containing four phases (two liquid phases of glycerol and lauric acid, air as gaseous phase, and a heterogeneous catalyst as solid phase). As a feasibility study, a chemometric model was generated for the pure components only. The quantities of lauric acid and the three products (mono-, di-, and trilaurin) were simultaneously determined over the course of the reaction with acceptable errors (1.8-12.5%) with regard to the calibration effort. This technology has the potential to give accurate results, particularly in unstable emulsion systems containing fats, oils, or emulsifiers, which are currently afflicted by analytical errors caused by the challenge of accurate sampling. PMID- 22047102 TI - Rapid eye movements during sleep in mice: high trait-like stability qualifies rapid eye movement density for characterization of phenotypic variation in sleep patterns of rodents. AB - BACKGROUND: In humans, rapid eye movements (REM) density during REM sleep plays a prominent role in psychiatric diseases. Especially in depression, an increased REM density is a vulnerability marker for depression. In clinical practice and research measurement of REM density is highly standardized. In basic animal research, almost no tools are available to obtain and systematically evaluate eye movement data, although, this would create increased comparability between human and animal sleep studies. METHODS: We obtained standardized electroencephalographic (EEG), electromyographic (EMG) and electrooculographic (EOG) signals from freely behaving mice. EOG electrodes were bilaterally and chronically implanted with placement of the electrodes directly between the musculus rectus superior and musculus rectus lateralis. After recovery, EEG, EMG and EOG signals were obtained for four days. Subsequent to the implantation process, we developed and validated an Eye Movement scoring in Mice Algorithm (EMMA) to detect REM as singularities of the EOG signal, based on wavelet methodology. RESULTS: The distribution of wakefulness, non-REM (NREM) sleep and rapid eye movement (REM) sleep was typical of nocturnal rodents with small amounts of wakefulness and large amounts of NREM sleep during the light period and reversed proportions during the dark period. REM sleep was distributed correspondingly. REM density was significantly higher during REM sleep than NREM sleep. REM bursts were detected more often at the end of the dark period than the beginning of the light period. During REM sleep REM density showed an ultradian course, and during NREM sleep REM density peaked at the beginning of the dark period. Concerning individual eye movements, REM duration was longer and amplitude was lower during REM sleep than NREM sleep. The majority of single REM and REM bursts were associated with micro-arousals during NREM sleep, but not during REM sleep. CONCLUSIONS: Sleep-stage specific distributions of REM in mice correspond to human REM density during sleep. REM density, now also assessable in animal models through our approach, is increased in humans after acute stress, during PTSD and in depression. This relationship can now be exploited to match animal models more closely to clinical situations, especially in animal models of depression. PMID- 22047103 TI - 3,4-dihydroxyphenylalanine-assisted hydroxyapatite nanoparticle coating on polymer scaffolds for efficient osteoconduction. AB - For bone regeneration applications, scaffolds made from a composite of a biodegradable polymer and ceramic have advantages over scaffolds made from only one component (biodegradable polymer or ceramic alone). In this study, a simple and rapid method was developed to induce hydroxyapatite (HA) nanoparticle adsorption on polyglycolic acid (PGA) scaffold surfaces. PGA meshes were coated with HA nanoparticles by immersing the scaffolds in a buffer solution containing 3,4-dihydroxyphenylalanine (DOPA), a critical, functional element in mussel adhesive protein known to strongly bind to various materials. Substantial HA coating on PGA scaffolds was achieved within 24 hours of immersion, as determined according to selective staining of ceramic particles, scanning electron microscopy, X-ray photoelectron spectroscopy, and energy-dispersive spectroscopy. To evaluate the osteoconduction efficacy of the scaffolds in vivo, PGA scaffolds, DOPA-coated PGA scaffolds, PGA scaffolds immersed in HA solution, and HA- and DOPA-coated PGA (HA-DOPA-PGA) scaffolds were implanted in critical-sized defects in mouse skulls for 8 weeks. Micro-computed tomography and histological analyses showed that bone regeneration in vivo was far more extensive on HA-DOPA-PGA scaffolds than on the other scaffolds. DOPA offers an efficient and simple method of HA coating on polymer scaffolds. HA-polymer composite scaffolds fabricated using this method could be useful as bone graft. PMID- 22047104 TI - Binding of 3,4,5,6-tetrahydroxyazepanes to the acid-beta-glucosidase active site: implications for pharmacological chaperone design for Gaucher disease. AB - Pharmacologic chaperoning is a therapeutic strategy being developed to improve the cellular folding and trafficking defects associated with Gaucher disease, a lysosomal storage disorder caused by point mutations in the gene encoding acid beta-glucosidase (GCase). In this approach, small molecules bind to and stabilize mutant folded or nearly folded GCase in the endoplasmic reticulum (ER), increasing the concentration of folded, functional GCase trafficked to the lysosome where the mutant enzyme can hydrolyze the accumulated substrate. To date, the pharmacologic chaperone (PC) candidates that have been investigated largely have been active site-directed inhibitors of GCase, usually containing five- or six-membered rings, such as modified azasugars. Here we show that a seven-membered, nitrogen-containing heterocycle (3,4,5,6-tetrahydroxyazepane) scaffold is also promising for generating PCs for GCase. Crystal structures reveal that the core azepane stabilizes GCase in a variation of its proposed active conformation, whereas binding of an analogue with an N-linked hydroxyethyl tail stabilizes GCase in a conformation in which the active site is covered, also utilizing a loop conformation not seen previously. Although both compounds preferentially stabilize GCase to thermal denaturation at pH 7.4, reflective of the pH in the ER, only the core azepane, which is a mid-micromolar competitive inhibitor, elicits a modest increase in enzyme activity for the neuronopathic G202R and the non-neuronopathic N370S mutant GCase in an intact cell assay. Our results emphasize the importance of the conformational variability of the GCase active site in the design of competitive inhibitors as PCs for Gaucher disease. PMID- 22047106 TI - Engineering an L-cell line that expresses insulin under the control of the glucagon-like peptide-1 promoter for diabetes treatment. AB - BACKGROUND: Diabetes mellitus is a complicated disease with a pathophysiology that includes hyperinsulinemia, hyperglycemia and other metabolic impairments leading to many clinical complications. It is necessary to develop appropriate treatments to manage the disease and reduce possible acute and chronic side effects. The advent of gene therapy has generated excitement in the medical world for the possible application of gene therapy in the treatment of diabetes. The glucagon-like peptide-1 (GLP-1) promoter, which is recognised by gut L-cells, is an appealing candidate for gene therapy purposes. The specific properties of L cells suggest that L-cells and the GLP-1 promoter would be useful for diabetes therapy approaches. RESULTS: In this study, L-cells were isolated from a primary intestinal cell line to create suitable target cells for insulin expression studies. The isolated cells displayed L-cell properties and were therefore used as an L-cell surrogate. Next, the isolated L-cells were transfected with the recombinant plasmid consisting of an insulin gene located downstream of the GLP-1 promoter. The secretion tests revealed that an increase in glucose concentration from 5 mM to 25 mM induced insulin gene expression in the L-cells by 2.7-fold. Furthermore, L-cells quickly responded to the glucose stimulation; the amount of insulin protein increased 2-fold in the first 30 minutes and then reached a plateau after 90 minutes. CONCLUSION: Our data showed that L-cells efficiently produced the mature insulin protein. In addition, the insulin protein secretion was positively regulated with glucose induction. In conclusion, GLP-1 promoter and L-cell could be potential candidates for diabetes gene therapy agents. PMID- 22047105 TI - Spinal muscular atrophy. AB - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. Estimated incidence is 1 in 6,000 to 1 in 10,000 live births and carrier frequency of 1/40 1/60. This disease is characterized by generalized muscle weakness and atrophy predominating in proximal limb muscles, and phenotype is classified into four grades of severity (SMA I, SMAII, SMAIII, SMA IV) based on age of onset and motor function achieved. This disease is caused by homozygous mutations of the survival motor neuron 1 (SMN1) gene, and the diagnostic test demonstrates in most patients the homozygous deletion of the SMN1 gene, generally showing the absence of SMN1 exon 7. The test achieves up to 95% sensitivity and nearly 100% specificity. Differential diagnosis should be considered with other neuromuscular disorders which are not associated with increased CK manifesting as infantile hypotonia or as limb girdle weakness starting later in life. Considering the high carrier frequency, carrier testing is requested by siblings of patients or of parents of SMA children and are aimed at gaining information that may help with reproductive planning. Individuals at risk should be tested first and, in case of testing positive, the partner should be then analyzed. It is recommended that in case of a request on carrier testing on siblings of an affected SMA infant, a detailed neurological examination should be done and consideration given doing the direct test to exclude SMA. Prenatal diagnosis should be offered to couples who have previously had a child affected with SMA (recurrence risk 25%). The role of follow-up coordination has to be managed by an expert in neuromuscular disorders and in SMA who is able to plan a multidisciplinary intervention that includes pulmonary, gastroenterology/nutrition, and orthopedic care. Prognosis depends on the phenotypic severity going from high mortality within the first year for SMA type 1 to no mortality for the chronic and later onset forms. PMID- 22047107 TI - Development of a peptide-targeted, myocardial ischemia-homing, mesenchymal stem cell. AB - Directing stem cells to the heart is critical in producing an effective cell therapy for myocardial infarction (MI). Mesenchymal stem cells (MSCs) offer an exquisite drug delivery platform with environment-sensing cytokine release and MSCs have shown therapeutic potential in MI. Peptide-based targeting offers a novel method to increase cell homing, wherein MI-specific peptides, identified by phage display, are synthesized with a palmitic acid tail to facilitate cell membrane integration. Phage-peptides were screened in a mouse MI model and four peptides (CRPPR, CRKDKC, KSTRKS, and CARSKNKDC) were selected and synthesized as palmitated derivatives for further investigation. Cell coating was optimized and coating persistence and cytotoxicity were evaluated. MSCs were coated with peptides, injected into mice with MI, and MSCs in the heart quantified. Greater numbers of MSCs were found in heart of animals treated with the peptide-coated MSCs compared to uncoated controls. MSC numbers had positive correlation with MI severity in peptide-coated cells but a negative correlation in MSCs alone. A transient cell coating ("painting") method has been developed that labels cells efficiently, non-toxically and increases cell localization in MI hearts. PMID- 22047108 TI - Quantum-chemical insights into the prediction of charge transport parameters for a naphthalenetetracarboxydiimide-based copolymer with enhanced electron mobility. AB - Theoretical modeling has been applied to study the charge transport (CT) parameters of a high-electron-mobility (n-type) naphthalenetetracarboxydiimide copolymer that was recently synthesized and tested for organic field-effect transistor applications. To understand the physicochemical characteristics of such a material, the intra- and intermolecular CT properties of holes and electrons were investigated using different DFT functionals, evidencing the need of range-separated hybrid functionals to predict key parameters such as the hole and electron reorganization energies. Our calculations revealed clear differences between hole- and electron-charging processes, providing fundamental elements for the rationalization of their transport. PMID- 22047109 TI - Effect of freezing time on macronutrients and energy content of breastmilk. AB - BACKGROUND: In neonatal units and human milk banks freezing breastmilk at less than -20 degrees C is the choice for preserving it. Scientific evidence in relation to the loss of nutritional quality during freezing is rare. Our main aim in this study is to determine the effect of freezing time up to 3 months on the content of fat, total nitrogen, lactose, and energy. Our secondary aim is to assess whether ultrasonic homogenization of samples enables a more suitable reading of breastmilk macronutrients with a human milk analyzer (HMA) (MIRIS, Uppsala, Sweden). METHODS: Refrigerated breastmilk samples were collected. Each sample was divided into six pairs of aliquots. One pair was analyzed on day 0, and the remaining pairs were frozen and analyzed, one each at 7, 15, 30, 60, and 90 days later. For each pair, one aliquot was homogenized by stirring, and the other by applying ultrasound. Samples were analyzed with the HMA. RESULTS: By 3 months from freezing with the two homogenization methods, we observed a relevant and significant decline in the concentration of fat and energy content. The modification of total nitrogen and lactose was not constant and of lower magnitude. The absolute concentration of all macronutrients and calories was greater with ultrasonic homogenization. CONCLUSIONS: After 3 months from freezing at -20 degrees C, an important decrease in fat and caloric content is observed. Correct homogenization is fundamental for correct nutritional analysis. PMID- 22047110 TI - Effect of Fluid Supplementation on Serum Bilirubin Level During Phototherapy of Exclusively Breastfed Term Infants with Hyperbilirubinemia. AB - Abstract Background: This study compared the rates of decrease in serum bilirubin levels in severely jaundiced healthy term infants given oral or intravenous fluid supplementation during phototherapy. Methods: A randomized controlled study was carried out in the neonatal intensive care unit of Zeynep Kamil Maternity and Children Hospital (Istanbul, Turkey) over a 4-month period. Two hundred fifty healthy term infants with hyperbilirubinemia were randomized to receive either solely breastmilk (n=125) or both breastmilk and intravenous fluid (n=125) during phototherapy. Results: There were no significant differences (p>0.05) in the mean birth weight, mean gestastional age, modes of delivery, mean time of admission age, mean serum osmolality, and hematocrit and reticulocyte count between the two groups. Similarly, there was no significant difference (p>0.05) in the mean indirect serum bilirubin level at the time of admission to the neonatal intensive care unit and at 4, 8, 12, 24, and 48 hours after commencement of phototherapy between the two groups. There was no significant difference (p>0.05) in the mean duration of phototherapy or in the median duration of hospitalization between the two groups. Conclusions: Based on our results, intravenous fluid support has no effect on the rate of decrease in serum bilirubin and decrease in duration of phototherapy in healthy term newborns with no dehydratation. However, using the oral route avoided the need for intravenous cannulae and their attendant complications. Insensible fluid loss is increased during phototherapy, so protection of hydration status with oral feeding is important for newborns. PMID- 22047111 TI - Molecular phylogeny of the higher and lower taxonomy of the Fusarium genus and differences in the evolutionary histories of multiple genes. AB - BACKGROUND: Species of the Fusarium genus are important fungi which is associated with health hazards in human and animals. The taxonomy of this genus has been a subject of controversy for many years. Although many researchers have applied molecular phylogenetic analysis to examine the taxonomy of Fusarium species, their phylogenetic relationships remain unclear only few comprehensive phylogenetic analyses of the Fusarium genus and a lack of suitable nucleotides and amino acid substitution rates. A previous stugy with whole genome comparison among Fusairum species revealed the possibility that each gene in Fusarium genomes has a unique evolutionary history, and such gene may bring difficulty to the reconstruction of phylogenetic tree of Fusarium. There is a need not only to check substitution rates of genes but also to perform the exact evaluation of each gene-evolution. RESULTS: We performed phylogenetic analyses based on the nucleotide sequences of the rDNA cluster region (rDNA cluster), and the beta tubulin gene (beta-tub), the elongation factor 1alpha gene (EF-1alpha), and the aminoadipate reductase gene (lys2). Although incongruence of the tree topologies between lys2 and the other genes was detected, all genes supported the classification of Fusarium species into 7 major clades, I to VII. To obtain a reliable phylogeny for Fusarium species, we excluded the lys2 sequences from our dataset, and re-constructed a maximum likelihood (ML) tree based on the combined data of the rDNA cluster, beta-tub, and EF-1alpha. Our ML tree indicated some interesting relationships in the higher and lower taxa of Fusarium species and related genera. Moreover, we observed a novel evolutionary history of lys2. We suggest that the unique tree topologies of lys2 are not due to an analytical artefact, but due to differences in the evolutionary history of genomes caused by positive selection of particular lineages. CONCLUSION: This study showed the reliable species tree of the higher and lower taxonomy in the lineage of the Fusarium genus. Our ML tree clearly indicated 7 major clades within the Fusarium genus. Furthermore, this study reported differences in the evolutionary histories among multiple genes within this genus for the first time. PMID- 22047112 TI - De minimis risk: a proposal for a new category of research risk. PMID- 22047113 TI - Should the "slow code" be resuscitated? AB - Most bioethicists and professional medical societies condemn the practice of "slow codes." The American College of Physicians ethics manual states, "Because it is deceptive, physicians or nurses should not perform half-hearted resuscitation efforts ('slow codes')." A leading textbook calls slow codes "dishonest, crass dissimulation, and unethical." A medical sociologist describes them as "deplorable, dishonest and inconsistent with established ethical principles." Nevertheless, we believe that slow codes may be appropriate and ethically defensible in situations in which cardiopulmonary resuscitation (CPR) is likely to be ineffective, the family decision makers understand and accept that death is inevitable, and those family members cannot bring themselves to consent or even assent to a do-not-resuscitate (DNR) order. In such cases, we argue, physicians may best serve both the patient and the family by having a carefully ambiguous discussion about end-of-life options and then providing resuscitation efforts that are less vigorous or prolonged than usual. PMID- 22047114 TI - The resuscitation of "slow codes": fraud, lies, and deception. PMID- 22047115 TI - Quick and limited is better than slow, sloppy, or sly. PMID- 22047116 TI - Faking it: unnecessary deceptions and the slow code. PMID- 22047117 TI - What is an "appropriate code"? PMID- 22047118 TI - Misadventures in CPR: neglecting nonmaleficent and advocacy obligations. PMID- 22047119 TI - Informed non-dissent: a better option than slow codes when families cannot bear to say "let her die". PMID- 22047120 TI - Let's Do Not Resuscitate Placebo Cardiopulmonary Resuscitation. PMID- 22047121 TI - The false dichotomy: do "everything" or give up. PMID- 22047122 TI - The "slow code" should be a "no code". PMID- 22047123 TI - Why not a transparent slow code? PMID- 22047124 TI - "You don't know me, but ...": access to patient data and subject recruitment in human subjects research. PMID- 22047125 TI - The role of cloud computing in managing the deluge of potentially private genetic data. PMID- 22047126 TI - Legitimate and ethical: distinguishing when and how regulations apply in patient oriented research. PMID- 22047127 TI - Saying privacy, meaning confidentiality. PMID- 22047128 TI - Clinicoradiological changes of brain NK/T cell lymphoma manifesting pure akinesia: a case report. AB - BACKGROUND: Pure akinesia (PA) is a distinct form of parkinsonism characterized by freezing phenomena. Little is known about brain tumor-associated PA. We highlight the clinicoradiological changes in a patient with PA and central nervous system (CNS) metastases of natural killer/T-cell lymphoma (NKTL). CASE PRESENTATION: A 68-year-old man with stage IVB extranodal NKTL developed a gait disturbance. Neurological examination of his gait revealed freezing, start hesitation, short step, forward flexion posture, festination and postural instability. Mild facial hypomimia and micrographia were observed. There was no rigidity or tremor in any of the four extremities. Brain magnetic resonance imaging (MRI) displayed T2-hyperintense lesions in the dorsal brainstem, cerebellum and periventricular white matter. Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) revealed hyperintensity in these regions. Cerebrospinal fluid cytology revealed CD56-positive cells on immunohistochemical staining. The patient's neurological deficits did not respond to L-dopa treatment and intrathecal administration of methotrexate (MTX). Two weeks later, he displayed confusion and generalized convulsions. T2-hyperintense lesions spread to the basal ganglia and the infratentorial regions. Gadolinium enhancement was observed in the cerebellum and frontal subcortex. DWI and the ADC revealed diffusion-restricted lesions in the middle cerebellar peduncles, left internal capsules and cerebral white matter. MTX pulse therapy and intrathecal administration of cytosine arabinoside and MTX were performed. Two months later, his ambulatory state was normalized. Brain MRI also revealed marked alleviation of the infratentorial and supratentorial lesions. CONCLUSIONS: The clinicoradiological profile of our patient suggested that dorsal ponto mesencephalic lesions could contribute to the pathogenesis of PA. Physicians should pay more attention to striking CNS seeding of metastatic NKTL. MTX pulse therapy had an excellent effect in improving serious symptoms and brain lesions in our patient. PMID- 22047129 TI - Kinetically controlled autocatalytic chemical process for bulk production of bimetallic core-shell structured nanoparticles. AB - Although bimetallic core@shell structured nanoparticles (NPs) are achieving prominence due to their multifunctionalities and exceptional catalytic, magnetic, thermal, and optical properties, the rationale underlying their design remains unclear. Here we report a kinetically controlled autocatalytic chemical process, adaptable for use as a general protocol for the fabrication of bimetallic core@shell structured NPs, in which a sacrificial Cu ultrathin layer is autocatalytically deposited on a dimensionally stable noble-metal core under kinetically controlled conditions, which is then displaced to form an active ultrathin metal-layered shell by redox-transmetalation. Unlike thermodynamically controlled under-potential deposition processes, this general strategy allows for the scaling-up of production of high-quality core-shell structured NPs, without the need for any additional reducing agents and/or electrochemical treatments, some examples being Pd@Pt, Pt@Pd, Ir@Pt, and Ir@Pd. Having immediate and obvious commercial potential, Pd@Pt NPs have been systematically characterized by in situ X-ray absorption, electrochemical-FTIR, transmission electron microscopy, and electrochemical techniques, both during synthesis and subsequently during testing in one particularly important catalytic reaction, namely, the oxygen reduction reaction, which is pivotal in fuel cell operation. It was found that the bimetallic Pd@Pt NPs exhibited a significantly enhanced electrocatalytic activity, with respect to this reaction, in comparison with their monometallic counterparts. PMID- 22047130 TI - Oral administration of the KATP channel opener diazoxide ameliorates disease progression in a murine model of multiple sclerosis. AB - BACKGROUND: Multiple Sclerosis (MS) is an acquired inflammatory demyelinating disorder of the central nervous system (CNS) and is the leading cause of nontraumatic disability among young adults. Activated microglial cells are important effectors of demyelination and neurodegeneration, by secreting cytokines and others neurotoxic agents. Previous studies have demonstrated that microglia expresses ATP-sensitive potassium (KATP) channels and its pharmacological activation can provide neuroprotective and anti-inflammatory effects. In this study, we have examined the effect of oral administration of KATP channel opener diazoxide on induced experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. METHODS: Anti-inflammatory effects of diazoxide were studied on lipopolysaccharide (LPS) and interferon gamma (IFNgamma)-activated microglial cells. EAE was induced in C57BL/6J mice by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55). Mice were orally treated daily with diazoxide or vehicle for 15 days from the day of EAE symptom onset. Treatment starting at the same time as immunization was also assayed. Clinical signs of EAE were monitored and histological studies were performed to analyze tissue damage, demyelination, glial reactivity, axonal loss, neuronal preservation and lymphocyte infiltration. RESULTS: Diazoxide inhibited in vitro nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) production and inducible nitric oxide synthase (iNOS) expression by activated microglia without affecting cyclooxygenase-2 (COX-2) expression and phagocytosis. Oral treatment of mice with diazoxide ameliorated EAE clinical signs but did not prevent disease. Histological analysis demonstrated that diazoxide elicited a significant reduction in myelin and axonal loss accompanied by a decrease in glial activation and neuronal damage. Diazoxide did not affect the number of infiltrating lymphocytes positive for CD3 and CD20 in the spinal cord. CONCLUSION: Taken together, these results demonstrate novel actions of diazoxide as an anti-inflammatory agent, which might contribute to its beneficial effects on EAE through neuroprotection. Treatment with this widely used and well-tolerated drug may be a useful therapeutic intervention in ameliorating MS disease. PMID- 22047133 TI - Operative Dentistry Home Page. PMID- 22047135 TI - Online Access. PMID- 22047131 TI - Low quality of routine microscopy for malaria at different levels of the health system in Dar es Salaam. AB - BACKGROUND: Laboratory capacity to confirm malaria cases in Tanzania is low and presumptive treatment of malaria is being practiced widely. In malaria endemic areas WHO now recommends systematic laboratory testing when suspecting malaria. Currently, the use of Rapid Diagnostic Tests (RDTs) is recommended for the diagnosis of malaria in lower level peripheral facilities, but not in health centres and hospitals. In this study, the following parameters were evaluated: (1) the quality of routine microscopy, and (2) the effects of RDT implementation on the positivity rate of malaria test results at three levels of the health system in Dar es Salaam, Tanzania. METHODS: During a baseline cross-sectional survey, routine blood slides were randomly picked from 12 urban public health facilities in Dar es Salaam, Tanzania. Sensitivity and specificity of routine slides were assessed against expert microscopy. In March 2007, following training of health workers, RDTs were introduced in nine public health facilities (three hospitals, three health centres and three dispensaries) in a near-to-programmatic way, while three control health facilities continued using microscopy. The monthly malaria positivity rates (PR) recorded in health statistics registers were collected before (routine microscopy) and after (routine RDTs) the intervention in all facilities. RESULTS: At baseline, 53% of blood slides were reported as positive by the routine laboratories, whereas only 2% were positive by expert microscopy. Sensitivity of routine microscopy was 71.4% and specificity was 47.3%. Positive and negative predictive values were 2.8% and 98.7%, respectively. Median parasitaemia was only three parasites per 200 white blood cells (WBC) by routine microscopy compared to 1226 parasites per 200 WBC by expert microscopy. Before RDT implementation, the mean test positivity rates using routine microscopy were 43% in hospitals, 62% in health centres and 58% in dispensaries. After RDT implementation, mean positivity rates using routine RDTs were 6%, 7% and 8%, respectively. The sensitivity and specificity of RDTs using expert microscopy as reference were 97.0% and 96.8%. The positivity rate of routine microscopy remained the same in the three control facilities: 71% before versus 72% after. Two cross-sectional health facility surveys confirmed that the parasite rate in febrile patients was low in Dar es Salaam during both the rainy season (13.6%) and the dry season (3.3%). CONCLUSIONS: The quality of routine microscopy was poor in all health facilities, regardless of their level. Over diagnosis was massive, with many false positive results reported as very low parasitaemia (1 to 5 parasites per 200 WBC). RDTs should replace microscopy as first-line diagnostic tool for malaria in all settings, especially in hospitals where the potential for saving lives is greatest. PMID- 22047136 TI - Spectroscopy of HF and HF-containing clusters in solid parahydrogen. AB - We report measurements of FT-IR absorption spectroscopy of HF, DF, and their clusters in solid parahydrogen (pH(2)). The observed spectra contain many absorption lines which were assigned to HF monomers, HF polymers, and clusters with other species, such as N(2), O(2), orthohydrogen (oH(2)), etc. The rotational constants of HF and DF monomers were determined from the cooperative transitions of the vibration of solid pH(2) and the rotation of HF and DF. Small reduction of the rotational constants indicates that HF and DF are nearly free rotors in solid pH(2). Time dependence of the spectra suggests that HF and DF monomers migrate in solid pH(2) and form larger polymers, probably via tunneling reactions through high energy barriers on inserting another monomer to the polymers. The line width of HF monomers in solid pH(2) was found to be 4 cm(-1), which is larger than that of other hydrogen halides in solid pH(2). This broad line width is explained by rapid rotational relaxation due to the accidental coincidence between the rotational energy of HF and the phonon energy with maximum density of states of solid pH(2) and the rotational-translational coupling in a trapping site. PMID- 22047137 TI - Low concentrations of honey reduce biofilm formation, quorum sensing, and virulence in Escherichia coli O157:H7. AB - Bacterial biofilms are associated with persistent infections due to their high resistance to antimicrobial agents. Hence, controlling pathogenic biofilm formation is important in bacteria-related diseases. Honey, at a low concentration of 0.5% (v/v), significantly reduced biofilm formation in enterohemorrhagic Escherichia coli O157:H7 without inhibiting the growth of planktonic cells. Conversely, this concentration did not inhibit commensal E. coli K-12 biofilm formation. Transcriptome analyses showed that honey significantly repressed curli genes (csgBAC), quorum sensing genes (AI-2 importer and indole biosynthesis), and virulence genes (LEE genes). Glucose and fructose in the honeys were found to be key components in reducing biofilm formation by E. coli O157:H7 through the suppression of curli production and AI-2 import. Furthermore, honey, glucose and fructose decreased the colonization of E. coli O157:H7 cells on human HT-29 epithelial cells. These results suggest that low concentrations of honey, such as in honeyed water, can be a practical means for reducing the colonization and virulence of pathogenic E. coli O157:H7. PMID- 22047138 TI - Room-temperature C-H arylation: merger of Pd-catalyzed C-H functionalization and visible-light photocatalysis. AB - This communication describes the development of a room-temperature ligand directed C-H arylation reaction using aryldiazonium salts. This was achieved by the successful merger of palladium-catalyzed C-H functionalization and visible light photoredox catalysis. The new method is general for a variety of directing groups and tolerates many common functional groups. PMID- 22047139 TI - RNA-Seq reveals genotype-specific molecular responses to water deficit in eucalyptus. AB - BACKGROUND: In a context of climate change, phenotypic plasticity provides long lived species, such as trees, with the means to adapt to environmental variations occurring within a single generation. In eucalyptus plantations, water availability is a key factor limiting productivity. However, the molecular mechanisms underlying the adaptation of eucalyptus to water shortage remain unclear. In this study, we compared the molecular responses of two commercial eucalyptus hybrids during the dry season. Both hybrids differ in productivity when grown under water deficit. RESULTS: Pyrosequencing of RNA extracted from shoot apices provided extensive transcriptome coverage - a catalog of 129,993 unigenes (49,748 contigs and 80,245 singletons) was generated from 398 million base pairs, or 1.14 million reads. The pyrosequencing data enriched considerably existing Eucalyptus EST collections, adding 36,985 unigenes not previously represented. Digital analysis of read abundance in 14,460 contigs identified 1,280 that were differentially expressed between the two genotypes, 155 contigs showing differential expression between treatments (irrigated vs. non irrigated conditions during the dry season), and 274 contigs with significant genotype-by treatment interaction. The more productive genotype displayed a larger set of genes responding to water stress. Moreover, stress signal transduction seemed to involve different pathways in the two genotypes, suggesting that water shortage induces distinct cellular stress cascades. Similarly, the response of functional proteins also varied widely between genotypes: the most productive genotype decreased expression of genes related to photosystem, transport and secondary metabolism, whereas genes related to primary metabolism and cell organisation were over-expressed. CONCLUSIONS: For the most productive genotype, the ability to express a broader set of genes in response to water availability appears to be a key characteristic in the maintenance of biomass growth during the dry season. Its strategy may involve a decrease of photosynthetic activity during the dry season associated with resources reallocation through major changes in the expression of primary metabolism associated genes. Further efforts will be needed to assess the adaptive nature of the genes highlighted in this study. PMID- 22047140 TI - Laccase-carrying electrospun fibrous membranes for adsorption and degradation of PAHs in shoal soils. AB - The removal of polycyclic aromatic hydrocarbons (PAHs) from soil is costly and time-consuming. The high hydrophobicity of PAHs makes PAH diffusion from soil particles by hydraulic flow difficult. The phase transfer of PAHs from soil to another available mediator is crucial for PAH removal. This study focuses on the remediation of PAH-contaminated shoal soil, located in Yangtze, China, using three types of laccase-carrying electrospun fibrous membranes (LCEFMs) fabricated via emulsion electrospinning. These LCEFMs were composed of core-shell structural nanofibers (for PAH adsorption), with laccase in the core (for PAH degradation) and pores on the shell (for mass transfer). The LCEFMs with strong adsorptivity extracted the PAHs from the soil particles, resulting in an obvious enhancement of PAH degradation. The removal efficiencies in 6 h for phenanthrene, fluoranthene, benz[a]anthracene and benzo[a]pyrene were greater than 95.1%, 93.2%, 79.1%, and 72.5%, respectively. The removal half-lives were 0.003-1.52 h, much shorter than those by free laccase (17.9-67.9 h) or membrane adsorption (1.25-12.50 h). The third-order reaction kinetics suggested that the superficial adsorption and internal diffusion were the rate-limiting steps of the overall reaction. A synergistic effect between adsorption and degradation was also proposed on the basis of the triple phase distribution and kinetics analyses. PMID- 22047141 TI - Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis. AB - BACKGROUND: Mitochondria have roles or appear to have roles in the pathogenesis of several chronic age-related and acute neurological disorders, including Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Parkinson's disease, and cerebral ischemia, and could be critical targets for development of rational mechanism-based, disease-modifying therapeutics for treating these disorders effectively. A deeper understanding of neural tissue mitochondria pathobiologies as definitive mediators of neural injury, disease, and cell death merits further study, and the development of additional tools to study neural mitochondria will help achieve this unmet need. RESULTS: We created transgenic mice that express the coral (Discosoma sp.) red fluorescent protein DsRed2 specifically in mitochondria of neurons using a construct engineered with a Thy1 promoter, specific for neuron expression, to drive expression of a fusion protein of DsRed2 with a mitochondrial targeting sequence. The biochemical and histological characterization of these mice shows the expression of mitochondrial-targeted DsRed2 to be specific for mitochondria and concentrated in distinct CNS regions, including cerebral cortex, hippocampus, thalamus, brainstem, and spinal cord. Red fluorescent mitochondria were visualized in cerebral cortical and hippocampal pyramidal neurons, ventrobasal thalamic neurons, subthalamic neurons, and spinal motor neurons. For the purpose of proof of principle application, these mice were used in excitotoxicity paradigms and double transgenic mice were generated by crossing Thy1-mitoDsRed2 mice with transgenic mice expressing enhanced-GFP (eGFP) under the control of the Hlxb9 promoter that drives eGFP expression specifically in motor neurons and by crossing Thy1-mitoDsRed2 mice to amyotrophic lateral sclerosis (ALS) mice expressing human mutant superoxide dismutase-1. CONCLUSIONS: These novel transgenic mice will be a useful tool for better understanding the biology of mitochondria in mouse and cellular models of human neurological disorders as exemplified by the mitochondrial swelling and fission seen in excitotoxicity and mouse ALS. PMID- 22047142 TI - Contralateral inguinal hernia after negative laparoscopic evaluation: a rare but real phenomenon. AB - BACKGROUND: The procedure of inguinal herniorrhaphy is the most common procedure performed by pediatric surgeons today. Laparoscopy has proved to be both sensitive and specific for evaluating the contralateral inguinal region. Despite the attractiveness that transinguinal laparoscopy offers and the success it has seen, we report a series of hernias after the utilization of this tool. METHODS: After IRB approval, a retrospective review of our institutions' experience from 1/2002 to 6/2010 with children who underwent unilateral inguinal hernia repair with contralateral evaluation with laparoscopy was completed. Data recorded included sex, age of initial presentation, laterality of initial hernia, age at second presentation, and operative time of initial surgery. RESULTS: From 2002 to 2010, 1291 patients underwent unilateral inguinal hernia repair with negative laparoscopic evaluation of the opposite ring. There were 32 patients (2.5%) who subsequently presented with an inguinal hernia on the contralateral side. All were men. The average age of initial presentation was 42.7 months. The mean time to occurrence of the contralateral hernia was found to be 16.7 months with a median of 12.2 months. The mean operative time for the initial operation was found to be 25.6 minutes. CONCLUSIONS: When using laparoscopy to explore the contralateral inguinal region, the surgeon should be aware that a negative exam may still be associated with a small chance of clinically developing a hernia. PMID- 22047143 TI - Single-incision laparoscopic colon and rectal surgery for pediatric inflammatory bowel disease and polyposis syndromes. AB - BACKGROUND: Minimally invasive procedures for inflammatory bowel disease have been shown to improve recovery in children. We report our initial experience with single-incision laparoscopic operations for pediatric intestinal disease. METHODS: We retrospectively reviewed 12 procedures in 11 patients (4 women) from March 2010 to January 2011. Procedures were conducted by using standard laparoscopic instruments. RESULTS: Mean age was 15 years (9-17 years). Procedures included three total abdominal colectomies, four two-stage ileal-pouch anal anastomosis (IPAA), two single-stage IPAA, two three-stage IPAA, and one ileocectomy. An accessory umbilical port was used in 6 cases. Mean operating time was 287 minutes. Mean length of stay was 4.1 days (3-9 days). Postoperative complications have occurred in 5 patients (42%). Anastomotic leak occurred in 2 patients with IPAA without protective ileostomy, 1 operative small bowel obstruction, 1 pelvic abscess and portal vein thrombosis, and 1 readmission for dehydration. Both patients who had leaked have recovered well and had their stomas reversed. Mean follow-up is 190 days. Average number of daily bowel movements is 4.5. Pouchitis has occurred in 50% (4/8) of patients. CONCLUSIONS: Single-incision laparoscopic surgery for pediatric intestinal disease is safe and feasible by using standard laparoscopic instruments. We do not advocate IPAA without a stoma due to the high rate of anastomotic leak. Continued experience will shorten operative times and reduce complications. PMID- 22047144 TI - The physiology and pathobiology of human kallikrein-related peptidase 6 (KLK6). AB - The human kallikrein-related peptidase 6 (KLK6) gene belongs to the 15-member kallikrein (KLK) gene family mapping to chromosome 19q13.3-13.4. Encoding for an enzyme with trypsin-like properties, KLK6 can degrade components of the extracellular matrix. The successful utilisation of another KLK member (KLK3/PSA) for prostate cancer diagnosis has led many to evaluate KLK6 as a potential biomarker for other cancer and diseased states. The observed dysregulated expression in cancers, neurodegenerative diseases and skin conditions has led to the discovery that KLK6 participates in other cellular pathways including inflammation, receptor activation and regulation of apoptosis. Moreover, the improvements in high-throughput genomics have not only enabled the identification of sequence polymorphisms, but of transcript variants, whose functional significances have yet to be realised. This comprehensive review will summarise the current findings of KLK6 pathophysiology and discuss its potential as a viable biomarker. PMID- 22047145 TI - The effect of hematocrit on the results of measurements using glucose meters based on different techniques. AB - BACKGROUND: The aim of the study was to evaluate the effect of hematocrit (HCT) on glucose meter assays based on different measurement techniques. METHODS: This paper studied glucose meters utilizing the glucose dehydrogenase reaction and four measurement techniques: colorimetry (HemoCue), reflectometry (Accu-Chek Active), amperometry (Optium Xido) and coulometry (Optium Omega). The EDTA venous blood samples HCT were modified by adding or removing defined aliquots of plasma. Glucose concentration was measured using each meter in 27 batches of blood samples, with HCT ranging from 20% to 60% in 10% increments. The data were analyzed using repeated measures models and a linear random effects model. RESULTS: A significant relationship between HCT and glucose reading in all meters was found and, for all meters except Optium Xido, there was a significant modification of this relationship by glucose level. The relative decrease in glucose concentration per 1% increase of the HCT value varied from 0.30% for Optium Omega in samples with glucose concentrations <5.55 mmol/L to 1.37% for Optium Xido in the same stratum (p<0.0001). The 5% glucose meter error (the ADA recommendation) was reached in the <5.55 mmol/L stratum after HCT change by 3.9% 16.7%. CONCLUSIONS: There is a significant continuous effect of HCT on measurement accuracy of glucose meters across its wide range of values and glucose concentrations. The most sensitive to the HCT interference was the system utilizing amperometric technique (Optium Xido) followed by the one with reflectometric technique (Accu-Chek Active), while the systems with the coulometric technique (Optium Omega) or colorimetric measurements in whole blood haemolysate (HemoCue) were less sensitive. PMID- 22047146 TI - High resolution time-of-flight mass analysis of the entire range of intact singly charged proteins. AB - The proof of principle for high-resolution analysis of intact singly charged proteins of any size is presented. Singly charged protein ions were produced by electrospray ionization followed by surface-induced charge reduction at atmospheric pressure. The inlet and trapping system "stops" the forward momentum of the protein ions over a very broad range to be captured by the digitally produced electric fields of a large radius linear ion trap whereupon they are moved into a smaller radius linear ion trap and collected and concentrated in front of its exit end-cap electrode using digital waveform manipulation. The protein ions are then ejected on demand from the end of the small radius linear quadrupole in a tightly collimated ion beam with an instrumentally defined kinetic energy into the acceleration region of an orthogonal acceleration reflectron time-of-flight mass analyzer where their flight times were measured and detected with a Photonis BiPolar TOF detector. We present results that clearly prove that massive singly charged ions can yield high-resolution mass spectra with very low chemical noise and without loss of sensitivity with increasing mass across the entire spectrum. Analysis of noncovalently bound protein complexes was demonstrated with streptavidin-Cy5 bound with a biotinylated peptide mimic. Our results suggest proteins across the entire range can be directly quantified using our mass analysis technique. We present evidence that solvent molecules noncovalently adduct onto the proteins while yielding consistent flight time distributions. Finally, we provide a look into future that will result from the ability to rapidly measure and quantify protein distributions. PMID- 22047147 TI - Bruce B Smith 1917-2007. PMID- 22047152 TI - Protein array diagnostics for guiding therapy in rheumatoid arthritis. AB - Early diagnosis and effective management of rheumatoid arthritis (RA) are pivotal, given the progressive, chronic, inflammatory, multi-systemic nature of the disease. Currently, proper initiation of adequate, individually tailored interventions in RA is delayed by the difficulty of early diagnosis and the limitations of disease activity and therapeutic response assessment tools. This is a significant challenge to rheumatologists, further complicated by the dynamic and progressively evolving autoimmune nature of RA, which is characterized by several immune mediators in a complex network that regulates the perpetuation of inflammation. Protein arrays constitute the most advanced current technology that can provide a comprehensive parallel analysis of this diverse network in RA, providing an individualized insight into immune status and host immune response. The last few years have seen significant transitions in the field of protein arrays, demonstrated by a technologic shift from the bench to the bedside, paving the way for the medical and scientific community to deliver patient-specific assessments and personalized management. Screening of protein arrays with sera or tissues from patients with RA enables the probing of immune responses and the identification of autoantibody signatures that can be used for the diagnosis and therapeutic management of patients. This article reviews the technology and the applications for protein arrays in the diagnosis and prognosis of RA. Clinical assessment tools could be derived from protein arrays, which may provide a means to continually track patients, allowing better evaluation of intervention strategies on a patient-specific basis and identification of diagnostic and disease activity biomarkers that could be used to guide optimal therapy in RA. PMID- 22047153 TI - Genotype-based dosing algorithms for warfarin therapy: data review and recommendations. AB - Warfarin, the most common oral anticoagulant, is the ideal candidate for pharmacogenetic dosing and gene-based 'individualization' of care. A plethora of studies have shown that stable dose requirements can be predicted using sequence variants in the CYP2C9 and VKORC1 genes in both sexes and in different races. Multiple clinical trials of pharmacogenetic warfarin dosing have been conducted with various methods, including several randomized trials that have been completed. These studies have reported varying degrees of success and some have been met with substantial skepticism. Other much larger randomized trials are ongoing. This paper reviews and synthesizes the various clinical trials that have been published and touches on the potential that the ongoing trials offer. The emergence of new oral anticoagulants also raises the question of the relevance of pharmacogenetic warfarin dosing for the future. The cost of genotype-guided dosing is substantial, and none of the studies to date have shown a cost-benefit of using pharmacogenetic warfarin dosing in clinical practice. Although pharmacogenetics-guided warfarin dosing has been discussed for many years, the currently available data regarding this genetically individualized dosing suggest that pharmacogenetics remains unproven for use in clinical warfarin prescription. PMID- 22047154 TI - Review of the relationship between C-reactive protein and exercise. AB - C-reactive protein (CRP), an acute phase reactant, is associated with systemic inflammation. Many studies have demonstrated that CRP levels have important prognostic implications for patients. For example, individuals with elevated CRP levels have an increased risk of cardiovascular events. The JUPITER study showed that reducing CRP levels can mitigate this risk. Various trials have investigated the effect of lifestyle modifications on serum CRP levels. Specifically, the impact of different exercise-based protocols on CRP levels has been researched. This review article evaluates the response of CRP levels to aerobic-based, resistance-based, and combination exercise protocols. Furthermore, it examines the impact of such regimens in children, adults, and the elderly. No definitive answers exist regarding the relationship between exercise and CRP levels. Significant reductions in CRP levels were noted in 11 of 25 trials of aerobic based regimens, two of five studies of combination protocols, and neither of two trials of resistance-based regimens. Similar findings were seen across all age groups. There were significant CRP reductions in nine of 18 adult studies, four of ten child studies, and one of three elderly studies. Mixed results reflect uncertainty about the ability of exercise to reduce inflammation. Various mechanisms, including increased protein synthesis and fat loss, have been proposed to explain the potential anti-inflammatory effects of exercise. While exercise-based regimens have produced inconsistent results, lifestyle modifications do appear to have significant anti-inflammatory effects. This was particularly evident in studies that utilized combined diet/exercise programs. Significant CRP reductions were seen in five of seven such trials. Interestingly, both studies with failed combination protocols achieved substantial CRP reductions in their diet-only groups. These findings suggest that weight loss is important in reducing inflammation. Additionally, they indicate that combined diet/exercise protocols should be part of any lifestyle intervention program. Further research will be needed to identify optimal regimens for achieving anti inflammatory benefits. PMID- 22047155 TI - Development of multiplex PCR method for the analysis of glutathione s-transferase polymorphism. AB - BACKGROUND: Busulfan is a key compound in myeloablative chemotherapy before hematopoietic stem-cell transplantation in children. Genetic polymorphisms of glutathione S-transferase (GST), which is involved in the metabolism of busulfan, have been implicated in interindividual variability in busulfan pharmacokinetics. Development of a rapid and simplified method for polygenic analysis of GST may facilitate large pharmacogenetic studies and clinical application of individualized busulfan dose adjustment. We previously introduced an effective PCR method for analyzing multiple genes using a small amount of DNA, termed 'TotalPlex amplification'. OBJECTIVE: The aim of this study was to extend the application of the TotalPlex method to the specific GST gene families (A1, P1, M1, and T1) that are related to busulfan metabolism, and thereby facilitate pharmacogenetic analysis of GST polymorphisms. METHODS: Seven genetic polymorphisms (GSTA1 promoter -52G>A, -69C>T, -567T>G, and -631T>G; GSTP1 313A>G; GSTM1 deletion; and GSTT1 deletion) were analyzed by multiplex PCR and genotyping, and the genotyping results from TotalPlex were verified with those from uniplex PCR. RESULTS: Using five pairs of specific bulging-specific primers, seven specific gene fragments were successfully amplified by multiplex amplification coupled to a multiplexed bead array detection system, with a smaller amount of DNA and a shorter process time than is needed for the conventional approach. The genotypes of seven loci from 30 different genomic DNA samples derived using the multiplex system were consistent with the results of standard genotyping methods. CONCLUSION: Our multiplex system provides a fast, inexpensive, and accurate method of detecting multiple GST polymorphisms (GSTA1, GSTP1, GSTM1, and GSTT1). PMID- 22047156 TI - Phenotypic analysis of HIV-1 genotypic drug-resistant isolates from China, using a single-cycle system. AB - BACKGROUND AND OBJECTIVES: Drug resistance in HIV-1 is one of the main causes of failure of antiretroviral therapy. Phenotypic detection of drug-resistant HIV-1 can provide guidance in selecting the optimal treatment regimen. Traditional phenotype assays are labor intensive and time consuming. Thus, a rapid and convenient phenotype assay with a single cycle of replication was developed and used in this study. METHODS: Two restriction endonuclease sites, ApaI and AgeI, were inserted into the plasmid pSG3Deltaenv(,) using site-directed mutagenesis. The reverse transcriptase and protease genes of HIV-1 were amplified from patients and cloned into the modified pSG3Deltaenv. Sixteen original recombinant pseudoviruses were generated. The phenotypic susceptibility of these 16 recombinant pseudoviruses to 12 antiretroviral drugs was determined using a luciferase reporter system, and the phenotype and genotype results were compared. RESULTS: A modified phenotype assay with a single-cycle system was established, and its reproducibility and feasibility were validated. Approximately 89% of the phenotype results were in agreement with the genotype results; this slight disagreement may have been due to complex and multiple resistance mutations. The phenotype results showed that individual pseudoviruses with four thymidine analog mutations (TAMs).[M41L, T67N, L210W, and T215Y] in combination with various other mutations had different levels of resistance to nucleoside reverse transcriptase inhibitors (NRTIs). Mutations E44A, T69D, and V118I influenced the pattern of resistance of TAMs. The level of resistance to non-NRTIs (NNRTIs) was also variable when different NNRTI-resistance mutations were combined. CONCLUSION: The single-cycle pseudovirus phenotypic susceptibility detection system reflects HIV 1 drug resistance, especially for complex resistance mutants, and could be used to screen new antiretroviral candidates. PMID- 22047158 TI - Biochemical properties of bioplastics made from wheat gliadins cross-linked with cinnamaldehyde. AB - The aim of this work has been to study the modification of gliadin films with cinnamaldehyde as a potential cross-linker agent. The molecular weight profile and cross-linking density showed that cinnamaldehyde increased reticulation in the resulting films. The participation of free amino groups of the protein in the newly created entanglements could be a possible mechanism of connection between the polypeptidic chains. The combination of a Schiff base and a Michael addition is a feasible approach to understanding this mechanism. The protein solubility in different media pointed to lower participation by both noncovalent and disulfide bonds in stabilizing the structure of the cross-linked films. The new covalent bonds formed by the cinnamaldehyde treatment hampered water absorption and weight loss, leading to more water-resistant matrices which had not disintegrated after 5 months. The properties of this novel bioplastic could be modified to suit the intended application by using cinnamaldehyde, a naturally occurring compound. PMID- 22047159 TI - Influence of Bifidobacterium bifidum on release of minerals from bread with differing bran content. AB - Bread is considered an important source of minerals; however, the presence of fiber and phytic acid reduces bioavailability of minerals from cereal products. It is well established that activity of microorganisms in human gut increases the amount of nutrients released during digestion. The aim of this study was to determine the influence of Bifidobacterium bifidum on release of some minerals from bread using an in vitro process of enzymatic digestion. White bread and with addition of 15, 30, or 45% of bran was baked in a bakery by traditional methods, with addition of yeasts and rye leaven, from flour made of wheat, Tonacja variety. Concentrations of calcium, magnesium, manganese, zinc, copper, and iron were determined by atomic absorption spectrometry. Bread was enzymatically digested in vitro without and with the addition of Bifidobacterium bifidum KD6 (inoculum 10(6) CFU/cm(3)) and percentages of minerals released were determined. The concentration of minerals released during enzymatic digestion varied depending upon the element, quantity of bran, and presence of bacteria. Increase in bran content decreased release of elements. Bifidobacterium bifidum KD6 enhanced amounts of magnesium and zinc released from all types of bread, while manganese and copper rose only from white bread with 15% bran addition. Bacteria decreased amounts of calcium and iron released from bread. Data indicate that diets rich in beneficial bacteria (probiotics) but not balanced with minerals might increase mineral deficiency. PMID- 22047160 TI - Translational research to develop a human PBPK models tool kit-volatile organic compounds (VOCs). AB - Toxicity and exposure evaluations remain the two of the key components of human health assessment. While improvement in exposure assessment relies on a better understanding of human behavior patterns, toxicity assessment still relies to a great extent on animal toxicity testing and human epidemiological studies. Recent advances in computer modeling of the dose-response relationship and distribution of xenobiotics in humans to important target tissues have advanced our abilities to assess toxicity. In particular, physiologically based pharmacokinetic (PBPK) models are among the tools than can enhance toxicity assessment accuracy. Many PBPK models are available to the health assessor, but most are so difficult to use that health assessors rarely use them. To encourage their use these models need to have transparent and user-friendly formats. To this end the Agency for Toxic Substances and Disease Registry (ATSDR) is using translational research to increase PBPK model accessibility, understandability, and use in the site specific health assessment arena. The agency has initiated development of a human PBPK tool-kit for certain high priority pollutants. The tool kit comprises a series of suitable models. The models are recoded in a single computer simulation language and evaluated for use by health assessors. While not necessarily being state-of-the-art code for each chemical, the models will be sufficiently accurate to use for screening purposes. This article presents a generic, seven-compartment PBPK model for six priority volatile organic compounds (VOCs): benzene (BEN), carbon tetrachloride (CCl(4)), dichloromethane (DCM), perchloroethylene (PCE), trichloroethylene (TCE), and vinyl chloride (VC). Limited comparisons of the generic and original model predictions to published kinetic data were conducted. A goodness of fit was determined by calculating the means of the sum of the squared differences (MSSDs) for simulation vs. experimental kinetic data using the generic and original models. Using simplified solvent exposure assumptions for oral ingestion and inhalation, steady-state blood concentrations of each solvent were simulated for exposures equivalent to the ATSDR Minimal Risk Levels (MRLs). The predicted blood levels were then compared to those reported in the National Health and Nutrition Examination Survey (NHANES). With the notable exception of BEN, simulations of combined oral and inhalation MRLs using our generic VOC model yielded blood concentrations well above those reported for the 95th percentile blood concentrations for the U.S. populations, suggesting no health concerns. When the PBPK tool kit is fully developed, risk assessors will have a readily accessible tool for evaluating human exposure to a variety of environmental pollutants. PMID- 22047161 TI - Evaluation of the interactions between multiwalled carbon nanotubes and Caco-2 cells. AB - The aim of this study was to determine whether multiwalled carbon nanotubes (MWNCT) are taken up by and are toxic to human intestinal enterocytes using the Caco-2 cell model. Caco-2 cells were exposed to 50 MUg/ml MWCNT (oxidized or pristine) for 24 h, and experiments were repeated in the presence of 2.5 mg/L natural organic matter. Cells displayed many of the properties that characterize enterocytes, such as apical microvilli, basolateral basement membrane, and glycogen. The cell monolayers also displayed tight junctions and electrical resistance. Exposure to pristine and oxidized MWCNT, with or without natural organic matter, did not markedly affect viability, which was assessed by measuring activity of released lactate dehydrogenase (LDH) and staining with propidium iodide. Ultrastructural analysis revealed some damage to microvilli colocalized with the MWCNT; however, neither type of MWCNT was taken up by Caco-2 cells. In contrast, pristine and oxidized MWCNT were taken up by the macrophage RAW 264.7 line. Our study suggests that intestinal enterocytes cells do not take up MWCNT. PMID- 22047163 TI - Dermal penetration potential of perfluorooctanoic acid (PFOA) in human and mouse skin. AB - Recent data, using a murine model, have indicated that dermal exposure to perfluorooctanoic acid (PFOA) induces immune modulation, suggesting that this may be an important route of PFOA exposure. To investigate the dermal penetration potential of PFOA, serum concentrations were analyzed in mice following topical application. Statistically significant and dose-responsive increases in serum PFOA concentrations were identified. In vitro dermal penetration studies also demonstrated that PFOA permeates both mouse and human skin. Investigation into the mechanisms mediating PFOA penetration demonstrated that dermal absorption was strongly dependent upon the ionization status of PFOA. In addition, PFOA solid, but not 1% PFOA/acetone solution, was identified as corrosive using a cultured epidermis in vitro model. Despite its corrosive potential, expression of inflammatory cytokines in the skin of topically exposed mice was not altered. These data suggest that PFOA is dermally absorbed and that under certain conditions the skin may be a significant route of exposure. PMID- 22047162 TI - Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico. AB - Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high percent urinary monomethylarsonic acid (MMA(V)), with several As-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic As metabolite. Some epidemiological studies suggested that indigenous Americans (AME) methylate As more efficiently; however, data supporting this have been equivocal. The aim of this study was to characterize the association between AME ancestry and As methylation efficiency using a panel of ancestry informative genetic markers to determine individual ancestry proportions in an admixed population (composed of two or more isolated ancestral populations) of 746 individuals environmentally exposed to As in northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3-1053.5 MUg/L, while percent AME (%AME) mean and range were 72.4 and 23-100. Adjusted (gender, age, AS3MT 7388/M287T haplotypes, body mass index [BMI], and TAs) multiple regression model showed that higher AME ancestry is significantly associated with lower percentage of urinary As excreted as MMA(V) (%uMMA) in this population (p < .01). Data also demonstrated a significant interaction between BMI and gender, indicating negative association between BMI and %uMMA, stronger in women than men (p < .01). Moreover, age and the AS3MT variants 7388 (intronic) and M287T (nonsynonymous) were also significantly associated with As methylation efficiency (p < .01). This study highlights the importance of BMI and indigenous American ancestry in some of the observed variability in As methylation efficiency, underscoring the need to be considered in epidemiology studies, particularly those carried out in admixed populations. PMID- 22047164 TI - Errors of alternative medicine: lessons for general practice. PMID- 22047165 TI - IPCRG: International Primary Care Respiratory Group. PMID- 22047166 TI - Hyperbaric oxygen and N-acetylcysteine treatment in L-arginine-induced acute pancreatitis in rats. AB - BACKGROUND: This study was designed to evaluate the combined effects of hyperbaric oxygen (HBO) and N-acetylcysteine (NAC) on acute necrotizing pancreatitis in rats. METHODS: Experiments were performed in 50 male Wistar rats, which were divided into five groups (N = 10 for each group). The first group received normal saline (0.9% NaCl) intraperitoneal and served as the control group. In the second group, acute pancreatitis was induced by 3.2-g/kg body weight L-arginine intraperitoneal twice at an interval of 1 hr, which has been shown previously to produce severe necrotizing acute pancreatitis. In the third group, NAC treatment (1000 mg/kg) was given after 1 hr of the induction of acute pancreatitis twice 24 hr apart. In the fourth group, animals received HBO, 6 hr after the induction of pancreatitis twice 12 hr apart. In the fifth group, animals received together NAC as in Group 3 and HBO treatment as in Group 4. Groups 1, 2, and 3 were left under normal atmospheric pressures. Twelve hours after last treatment, the animals were killed by exsanguinations. Blood samples were studied for amylase, calcium, and lactate dehydrogenase (LDH), pancreatic histology, pancreatic tissue malondialdehyde, superoxide dismutase, and glutathione levels. RESULTS: Acute pancreatitis is reduced by the treatment of NAC, HBO, NAC + HBO. HBO + NAC groups performed statistically the best in preventing L-arginine-induced acute necrotising pancreatitis. CONCLUSIONS: NAC especially combined with HBO, decreases oxidative stress parameters, serum amylase, calcium, and LDH levels, as well as histopathologic score. PMID- 22047167 TI - Maternal exposure to air pollution before and during pregnancy related to changes in newborn's cord blood lymphocyte subpopulations. The EDEN study cohort. AB - BACKGROUND: Toxicants can cross the placenta and expose the developing fetus to chemical contamination leading to possible adverse health effects, by potentially inducing alterations in immune competence. Our aim was to investigate the impacts of maternal exposure to air pollution before and during pregnancy on newborn's immune system. METHODS: Exposure to background particulate matter less than 10 MUm in diameter (PM10) and nitrogen dioxide (NO2) was assessed in 370 women three months before and during pregnancy using monitoring stations. Personal exposure to four volatile organic compounds (VOCs) was measured in a subsample of 56 non smoking women with a diffusive air sampler during the second trimester of pregnancy. Cord blood was analyzed at birth by multi-parameter flow cytometry to determine lymphocyte subsets. RESULTS: Among other immunophenotypic changes in cord blood, decreases in the CD4+CD25+ T-cell percentage of 0.82% (p = 0.01), 0.71% (p = 0.04), 0.88% (p = 0.02), and 0.59% (p = 0.04) for a 10 MUg/m3 increase in PM10 levels three months before and during the first, second and third trimester of pregnancy, respectively, were observed after adjusting for confounders. A similar decrease in CD4+CD25+ T-cell percentage was observed in association with personal exposure to benzene. A similar trend was observed between NO2 exposure and CD4+CD25+ T-cell percentage; however the association was stronger between NO2 exposure and an increased percentage of CD8+ T-cells. CONCLUSIONS: These data suggest that maternal exposure to air pollution before and during pregnancy may alter the immune competence in offspring thus increasing the child's risk of developing health conditions later in life, including asthma and allergies. PMID- 22047168 TI - Photonic control of surface anchoring on solid colloids dispersed in liquid crystals. AB - The anchoring of liquid-crystal (LC) mesogens to the surfaces of colloids is an important factor in determining intercolloidal interactions and the symmetry of the ensuing colloidal assembly in nematic colloids. The dynamic control of surface anchoring could therefore provide a handle to tune the colloidal organization and resulting properties in these systems. In this article, we report our results on the study of thermotropic nematic LC (E7) dispersions of silica and glass microcolloids bearing photosensitive surface azobenzene groups. By the photoinduced modulation of the colloidal-LC interfacial properties, due to the trans-cis isomerization of azobenzene units, we tune the anchoring on silica colloids from homeotropic (trans-azobenzene) to homogeneous planar (cis azobenzene) reversibly. In tune with the change in surface anchoring, the interparticle interactions were also dictated by dipolar and quadrupolar symmetries for homeotropic and homogeneous planar anchoring, respectively. In our experiments, we find that, in addition to the isomerization state of the surface bound azobenzene units, the nature of the colloid plays a crucial role in determining the anchoring state obtained on applying photostimuli. We also study the LC anchoring on colloids as a function of the azobenzene surface density and find that beyond a threshold value the anchoring properties remain invariant. PMID- 22047169 TI - Self-assembling of zinc phthalocyanines on ZnO (1010) surface through multiple time scales. AB - We adopt a hierarchic combination of theoretical methods to study the assembling of zinc phthalocyanines (ZnPcs) on a ZnO (1010) surface through multiple time scales. Atomistic simulations, such as model potential molecular dynamics and metadynamics, are used to study the energetics and short time evolution (up to ~100 ns) of small ZnPc aggregates. The stability and the lifetime of large clusters is then studied by means of an atomistically informed coarse-grained model using classical molecular dynamics. Finally, the macroscopic time scale clustering phenomenon is studied by Metropolis Monte Carlo algorithms as a function of temperature and surface coverage. We provide evidence that at room temperature the aggregation is likely to occur at sufficiently high coverage, and we characterize the nature, morphology, and lifetime of ZnPc's clusters. We identify the molecular stripes oriented along [010] crystallographic directions as the most energetically stable aggregates. PMID- 22047171 TI - Comparative reactivity of ferric-superoxo and ferryl-oxo species in heme and non heme complexes. AB - Ferryl-oxo species have been recognized as a key oxidant in many heme and non heme enzymes. Recently, less-characterized ferric-superoxo species have been found or suggested to be another electrophilic oxidant. Reactivity of several vital ferryl-oxo and ferric-superoxo model complexes was examined by DFT calculations. Reactivity is found to correlate well with thermodynamic driving force and can increase with higher electrophilicity of the oxidant. Reactivity of the ferric-superoxo oxidants generally is not "superior" to the ferryl-oxo ones. Compared to the high-spin non-heme ferric-superoxo, the lower reactivity of low spin heme ferric-superoxo, seldom utilized in nature, can be attributed to lower electrophilicity and more pronounced quenching of anti-ferromagnetic coupling between the ferric and superoxo parts. The present comparison should shed some light on mechanistic strategies in heme and non-heme enzymes and provide clues to rational design of ferric-superoxo oxidants. PMID- 22047170 TI - The contribution of activated astrocytes to Abeta production: implications for Alzheimer's disease pathogenesis. AB - BACKGROUND: beta-Amyloid (Abeta) plays a central role in Alzheimer's disease (AD) pathogenesis. Neurons are major sources of Abeta in the brain. However, astrocytes outnumber neurons by at least five-fold. Thus, even a small level of astrocytic Abeta production could make a significant contribution to Abeta burden in AD. Moreover, activated astrocytes may increase Abeta generation. beta-Site APP cleaving enzyme 1 (BACE1) cleavage of amyloid precursor protein (APP) initiates Abeta production. Here, we explored whether pro-inflammatory cytokines or Abeta42 would increase astrocytic levels of BACE1, APP, and beta-secretase processing, implying a feed-forward mechanism of astrocytic Abeta production. METHODS: Mouse primary astrocytes were treated with combinations of LPS, TNF alpha, IFN-gamma, and IL-1beta and analyzed by immunoblot and ELISA for endogenous BACE1, APP, and secreted Abeta40 levels. Inhibition of JAK and iNOS signaling in TNF-alpha+IFN-gamma-stimulated astrocytes was also analyzed. In addition, C57BL/6J or Tg2576 mouse astrocytes were treated with oligomeric or fibrillar Abeta42 and analyzed by immunoblot for levels of BACE1, APP, and APPsbetasw. Astrocytic BACE1 and APP mRNA levels were measured by TaqMan RT-PCR. RESULTS: TNF-alpha+IFN-gamma stimulation significantly increased levels of astrocytic BACE1, APP, and secreted Abeta40. BACE1 and APP elevations were post transcriptional at early time-points, but became transcriptional with longer TNF alpha+IFN-gamma treatment. Despite a ~4-fold increase in astrocytic BACE1 protein level following TNF-alpha+IFN-gamma stimulation, BACE1 mRNA level was significantly decreased suggesting a post-transcriptional mechanism. Inhibition of iNOS and JAK did not reduce TNF-alpha+IFN-gamma-stimulated elevation of astrocytic BACE1, APP, and Abeta40, except that JAK inhibition blocked the APP increase. Finally, oligomeric and fibrillar Abeta42 dramatically increased levels of astrocytic BACE1, APP, and APPsbetasw through transcriptional mechanisms, at least in part. CONCLUSIONS: Cytokines including TNF-alpha+IFN-gamma increase levels of endogenous BACE1, APP, and Abeta and stimulate amyloidogenic APP processing in astrocytes. Oligomeric and fibrillar Abeta42 also increase levels of astrocytic BACE1, APP, and beta-secretase processing. Together, our results suggest a cytokine- and Abeta42-driven feed-forward mechanism that promotes astrocytic Abeta production. Given that astrocytes greatly outnumber neurons, activated astrocytes may represent significant sources of Abeta during neuroinflammation in AD. PMID- 22047172 TI - Social cues at encoding affect memory in 4-month-old infants. AB - Available evidence suggests that infants use adults' social cues for learning by the second half of the first year of life. However, little is known about the short-term or long-term effects of joint attention interactions on learning and memory in younger infants. In the present study, 4-month-old infants were familiarized with visually presented objects in either of two conditions that differed in the degree of joint attention (high vs. low). Brain activity in response to familiar and novel objects was assessed immediately after the familiarization phase (immediate recognition), and following a 1-week delay (delayed recognition). The latency of the Nc component differentiated between recognition of old versus new objects. Pb amplitude and latency were affected by joint attention in delayed recognition. Moreover, the frequency of infant gaze to the experimenter during familiarization differed between the two experimental groups and modulated the Pb response. Results show that joint attention affects the mechanisms of long-term retention in 4-month-old infants. We conclude that joint attention helps children at this young age to recognize the relevance of learned items. PMID- 22047174 TI - Analysis of natural variation of the potato tuber proteome reveals novel candidate genes for tuber bruising. AB - Potato (Solanum tuberosum) presents a challenging organism for the genetic and molecular dissection of complex traits due to its tetraploidy and high heterozygosity. One such complex trait of high agronomic interest is the tuber susceptibility to bruising upon mechanical impact, which involves an enzymatic browning reaction. We have compared the tuber proteome of two groups of 10 potato cultivars differing in bruising susceptibility to (i) identify de novo proteins that contribute to bruising, based on differential protein expression, and (ii) validate these proteins by combining proteomics with association genetics. The comparison of 20 potato varieties yields insight into the high natural variation of tuber protein patterns due to genetic background. Seven genes or gene families were found that were both differentially expressed on the protein level between groups and for which DNA polymorphisms were associated with the investigated traits. A putative class III lipase was identified as a novel factor contributing to the natural variation of bruising. Additionally, tuber proteome changes triggered by mechanical impact, within and between groups, were monitored over time. Differentially expressed proteins were found, notably lipases, patatins, and annexins, showing remarkable time-dependent protein variation. PMID- 22047173 TI - Variations of insecticide residual bio-efficacy on different types of walls: results from a community-based trial in south Cameroon. AB - BACKGROUND: Determination of residual activity of insecticides is essential information for the selection of appropriate indoor spraying operation. The present study was undertaken to evaluate the residual effect of three candidate insecticide formulations on different indoor surfaces in order to guide future interventions, in the context of Cameroon and other African countries. METHODS: The study was conducted in the Ntougou neighbourhood in Yaounde (capital city of Cameroon). Bendiocarb WP, lambda-cyhalothrin CS and deltamethrin WG were sprayed on the indoor wall surfaces of local cement, wood and mud houses. Their effects on the knockdown and mortality of the Kisumu susceptible strain of Anopheles gambiae s.s were assessed each month from March to September 2009, using the WHO plastic cones test. Knockdown and mortality rates were compared between different surfaces using Chi-square test. A Kaplan-Meir model was used to estimate the time of treatment failure. RESULTS: With bendiocarb WP, the knockdown rates were frequently above 98% during 13 weeks after spraying, except on mud walls where it significantly decreased at the 13th week (P < 0.05). With lambda cyhalothrin CS, the knockdown rates remained 100% on wood surfaces during the 26 weeks trial. However, it significantly decreased on concrete and mud surfaces from the 11th (83%) and the 20th (88%) weeks respectively (P < 0.05). With deltamethrin WG, it remained high on concrete surfaces during 26 weeks (> 98%); while it varied between 60 and 100% on wood or mud surfaces. The survival estimates of bendiocarb WP treatments remaining effective in killing An. gambiae s.s. (mortality rate >= 80%) was > 13 weeks on cement and wood surfaces and 13 weeks on mud surfaces. Those of lambda-cyhalothrin CS were > 26 weeks on wood surfaces, and 20 weeks on concrete and mud surfaces. By contrast, those of deltamethrin WG were 26 weeks on concrete, 20 weeks on mud surfaces and 15 weeks on wood surfaces. CONCLUSION: Current data suggest variable durations of spray cycles for each product, according to the type of wall surfaces, highlighting the importance of testing candidate products in local context before using them in large scale. PMID- 22047175 TI - Practical considerations to guide development of access controls and decision support for genetic information in electronic medical records. AB - BACKGROUND: Genetic testing is increasingly used as a tool throughout the health care system. In 2011 the number of clinically available genetic tests is approaching 2,000, and wide variation exists between these tests in their sensitivity, specificity, and clinical implications, as well as the potential for discrimination based on the results. DISCUSSION: As health care systems increasingly implement electronic medical record systems (EMRs) they must carefully consider how to use information from this wide spectrum of genetic tests, with whom to share information, and how to provide decision support for clinicians to properly interpret the information. Although some characteristics of genetic tests overlap with other medical test results, there are reasons to make genetic test results widely available to health care providers and counterbalancing reasons to restrict access to these test results to honor patient preferences, and avoid distracting or confusing clinicians with irrelevant but complex information. Electronic medical records can facilitate and provide reasonable restrictions on access to genetic test results and deliver education and decision support tools to guide appropriate interpretation and use. SUMMARY: This paper will serve to review some of the key characteristics of genetic tests as they relate to design of access control and decision support of genetic test information in the EMR, emphasizing the clear need for health information technology (HIT) to be part of optimal implementation of genetic medicine, and the importance of understanding key characteristics of genetic tests when designing HIT applications. PMID- 22047176 TI - Ultrafast dynamics of isolated fluorenone. AB - The ultrafast dynamics of isolated 9-fluorenone was studied by femtosecond time resolved photoionization and photoelectron spectroscopy. The molecule was excited around 264-266 nm into the S(6) state. The experimental results indicate that the excitation is followed by a multistep deactivation. A time constant of 50 fs or less corresponds to a fast redistribution of energy within the initially excited manifold of states, i.e., a motion away from the Franck-Condon region. Internal conversion to the S(1) state then proceeds within 0.4 ps. The S(1) state is long lived, and only a lower bound of 20 ps can be derived. In addition, we computed excited state energies and oscillator strengths by TD-DFT theory, supporting the interpretation of the experimental data. PMID- 22047177 TI - Preparation of single-stranded DNA from PCR products with streptavidin magnetic beads. AB - The preparation of single-stranded DNA from double-stranded PCR products is an essential step in the identification of aptamers by Systematic Evolution of Ligands by EXponential enrichment (SELEX). The most widely used method for producing single-stranded DNA is alkaline denaturation of biotinylated PCR products attached to streptavidin-coated magnetic beads. Recently, it has been suggested that this method may be unsuitable due to the release of interfering amounts of streptavidin and biotinylated DNA. In this article, the alkaline method is compared with a thermal method that is known to release significant amounts of streptavidin and biotinylated DNA. Results show that trace amounts of streptavidin and biotinylated DNA are released in the alkaline method, but this can be curtailed by preconditioning the beads in aqueous sodium hydroxide. The main product in the alkaline method is single-stranded DNA, which is produced in high yield. PMID- 22047178 TI - Improvement of tetracaine antinociceptive effect by inclusion in cyclodextrins. AB - Local anesthetics (LA) are among the most important pharmacological compounds used to attenuate or eliminate pain. However, systemic toxicity is still a limitation for LA application, especially for ester-type drugs, such as tetracaine (TTC) that presents poor chemical stability (due to hydrolysis by plasma esterases). Several approaches have been used to improve LA pharmaceutical properties, including the employment of drug-delivery systems. Here we used beta cyclodextrin (beta-CD) or hydroxypropyl-beta-cyclodextrin (HP-beta-CD) to develop two new TTC formulations (TTC:beta-CD and TTC:HP-beta-CD). The inclusion complexes formation, in a 1:1 stoichiometry, was confirmed by differential scanning calorimetry, X-ray diffraction, UV-VIS absorption and fluorescence. Nuclear magnetic resonance (DOSY experiments) revealed that TTC association with HP-beta-CD is stronger (Ka=1200 mol/L(-1)) than with beta-CD (Ka=845 mol/L(-1)). Moreover, nuclear Overhauser effect (NOE) experiments provided information on the topology of the complexes, where TTC aromatic ring is buried inside the CD hydrophobic cavity. In vitro tests with 3T3 fibroblast cells culture revealed that complexation decreased TTC cytotoxicity. In addition, the total analgesic effect of TTC, tested in rats through the infraorbital nerve test, was improved in 36% with TTC:beta-CD and TTC:HP-beta-CD. In conclusion, these formulations presented potential for future clinical use, by reducing the toxicity and increasing the antinociceptive effect of tetracaine. PMID- 22047181 TI - Experiences of female survivors of sexual violence in eastern Democratic Republic of the Congo: a mixed-methods study. AB - BACKGROUND: The conflict in eastern Democratic Republic of the Congo (DRC) is the deadliest since World War II. Over a decade of fighting amongst an array of armed groups has resulted in extensive human rights abuses, particularly the widespread use of sexual violence against women. METHODS: Using a mixed-methods approach, we surveyed a non-random sample of 255 women attending a referral hospital and two local non-governmental organizations to characterize their experiences of sexual and gender-based violence (SGBV). We then conducted focus groups of 48 women survivors of SGBV to elaborate on survey findings. Quantitative and qualitative data underwent thematic and statistical analysis respectively. FINDINGS: Of the women surveyed, 193 (75.7%) experienced rape. Twenty-nine percent of raped women were rejected by their families and 6% by their communities. Thirteen percent of women had a child from rape. Widowhood, husband abandonment, gang rape, and having a child from rape were significant risk factors for social rejection. Mixed methods findings show rape survivors were seen as "contaminated" with HIV, contributing to their isolation and over 95% could not access prophylactic care in time. Receiving support from their husbands after rape was protective against survivors' feelings of shame and social isolation. INTERPRETATION: Rape results not only in physical and psychological trauma, but can destroy family and community structures. Women face significant obstacles in seeking services after rape. Interventions offering long-term solutions for hyper-vulnerable women are vital, but lacking; reintegration programs on SGBV for women, men, and communities are also needed. PMID- 22047179 TI - Metal selectivity of the Escherichia coli nickel metallochaperone, SlyD. AB - SlyD is a Ni(II)-binding protein that contributes to nickel homeostasis in Escherichia coli. The C-terminal domain of SlyD contains a rich variety of metal binding amino acids, suggesting broader metal binding capabilities, and previous work demonstrated that the protein can coordinate several types of first-row transition metals. However, the binding of SlyD to metals other than Ni(II) has not been previously characterized. To improve our understanding of the in vitro metal-binding activity of SlyD and how it correlates with the in vivo function of this protein, the interactions between SlyD and the series of biologically relevant transition metals [Mn(II), Fe(II), Co(II), Cu(I), and Zn(II)] were examined by using a combination of optical spectroscopy and mass spectrometry. Binding of SlyD to Mn(II) or Fe(II) ions was not detected, but the protein coordinates multiple ions of Co(II), Zn(II), and Cu(I) with appreciable affinity (K(D) values in or below the nanomolar range), highlighting the promiscuous nature of this protein. The order of affinities of SlyD for the metals examined is as follows: Mn(II) and Fe(II) < Co(II) < Ni(II) ~ Zn(II) ? Cu(I). Although the purified protein is unable to overcome the large thermodynamic preference for Cu(I) and exclude Zn(II) chelation in the presence of Ni(II), in vivo studies reveal a Ni(II)-specific function for the protein. Furthermore, these latter experiments support a specific role for SlyD as a [NiFe]-hydrogenase enzyme maturation factor. The implications of the divergence between the metal selectivity of SlyD in vitro and the specific activity in vivo are discussed. PMID- 22047180 TI - Transcript and metabolite analysis in Trincadeira cultivar reveals novel information regarding the dynamics of grape ripening. AB - BACKGROUND: Grapes (Vitis vinifera L.) are economically the most important fruit crop worldwide. However, the complexity of molecular and biochemical events that lead to the onset of ripening of nonclimacteric fruits is not fully understood which is further complicated in grapes due to seasonal and cultivar specific variation. The Portuguese wine variety Trincadeira gives rise to high quality wines but presents extremely irregular berry ripening among seasons probably due to high susceptibility to abiotic and biotic stresses. RESULTS: Ripening of Trincadeira grapes was studied taking into account the transcriptional and metabolic profilings complemented with biochemical data. The mRNA expression profiles of four time points spanning developmental stages from pea size green berries, through veraison and mature berries (EL 32, EL 34, EL 35 and EL 36) and in two seasons (2007 and 2008) were compared using the Affymetrix GrapeGen(r) genome array containing 23096 probesets corresponding to 18726 unique sequences. Over 50% of these probesets were significantly differentially expressed (1.5 fold) between at least two developmental stages. A common set of modulated transcripts corresponding to 5877 unigenes indicates the activation of common pathways between years despite the irregular development of Trincadeira grapes. These unigenes were assigned to the functional categories of "metabolism", "development", "cellular process", "diverse/miscellanenous functions", "regulation overview", "response to stimulus, stress", "signaling", "transport overview", "xenoprotein, transposable element" and "unknown". Quantitative RT-PCR validated microarrays results being carried out for eight selected genes and five developmental stages (EL 32, EL 34, EL 35, EL 36 and EL 38). Metabolic profiling using 1H NMR spectroscopy associated to two-dimensional techniques showed the importance of metabolites related to oxidative stress response, amino acid and sugar metabolism as well as secondary metabolism. These results were integrated with transcriptional profiling obtained using genome array to provide new information regarding the network of events leading to grape ripening. CONCLUSIONS: Altogether the data obtained provides the most extensive survey obtained so far for gene expression and metabolites accumulated during grape ripening. Moreover, it highlighted information obtained in a poorly known variety exhibiting particular characteristics that may be cultivar specific or dependent upon climatic conditions. Several genes were identified that had not been previously reported in the context of grape ripening namely genes involved in carbohydrate and amino acid metabolisms as well as in growth regulators; metabolism, epigenetic factors and signaling pathways. Some of these genes were annotated as receptors, transcription factors, and kinases and constitute good candidates for functional analysis in order to establish a model for ripening control of a non-climacteric fruit. PMID- 22047182 TI - Transcriptome analysis of Bupleurum chinense focusing on genes involved in the biosynthesis of saikosaponins. AB - BACKGROUND: Bupleurum chinense DC. is a widely used traditional Chinese medicinal plant. Saikosaponins are the major bioactive constituents of B. chinense, but relatively little is known about saikosaponin biosynthesis. The 454 pyrosequencing technology provides a promising opportunity for finding novel genes that participate in plant metabolism. Consequently, this technology may help to identify the candidate genes involved in the saikosaponin biosynthetic pathway. RESULTS: One-quarter of the 454 pyrosequencing runs produced a total of 195, 088 high-quality reads, with an average read length of 356 bases (NCBI SRA accession SRA039388). A de novo assembly generated 24, 037 unique sequences (22, 748 contigs and 1, 289 singletons), 12, 649 (52.6%) of which were annotated against three public protein databases using a basic local alignment search tool (E-value <=1e-10). All unique sequences were compared with NCBI expressed sequence tags (ESTs) (237) and encoding sequences (44) from the Bupleurum genus, and with a Sanger-sequenced EST dataset (3, 111). The 23, 173 (96.4%) unique sequences obtained in the present study represent novel Bupleurum genes. The ESTs of genes related to saikosaponin biosynthesis were found to encode known enzymes that catalyze the formation of the saikosaponin backbone; 246 cytochrome P450 (P450s) and 102 glycosyltransferases (GTs) unique sequences were also found in the 454 dataset. Full length cDNAs of 7 P450s and 7 uridine diphosphate GTs (UGTs) were verified by reverse transcriptase polymerase chain reaction or by cloning using 5' and/or 3' rapid amplification of cDNA ends. Two P450s and three UGTs were identified as the most likely candidates involved in saikosaponin biosynthesis. This finding was based on the coordinate up-regulation of their expression with beta-AS in methyl jasmonate-treated adventitious roots and on their similar expression patterns with beta-AS in various B. chinense tissues. CONCLUSIONS: A collection of high-quality ESTs for B. chinense obtained by 454 pyrosequencing is provided here for the first time. These data should aid further research on the functional genomics of B. chinense and other Bupleurum species. The candidate genes for enzymes involved in saikosaponin biosynthesis, especially the P450s and UGTs, that were revealed provide a substantial foundation for follow-up research on the metabolism and regulation of the saikosaponins. PMID- 22047183 TI - Hippocampal integrity and neurocognition in first-episode schizophrenia: a multidimensional study. AB - OBJECTIVES: Impairments in memory and executive function are key components of schizophrenia. These disturbances have been linked to several subcortical and cortical networks. For example, anatomical and functional changes in the hippocampus have been linked to deficits in these cognitive domains. However, the association between hippocampal morphometry, neurochemistry and function is controversial. Therefore, we aimed to investigate the relationship between hippocampal anomalies and their functional relevance. METHODS: Fifty-seven first episode schizophrenia patients (FE-SZ) and 61 healthy control subjects (HC) participated in this study. Hippocampal volumes were investigated using structural magnetic resonance imaging (sMRI) and hippocampal neurochemistry was determined using proton magnetic resonance spectroscopy (1H MRS). Verbal memory was used as a hippocampus-dependent cognitive task whereas working memory and cognitive flexibility assessed frontal lobe function. RESULTS: FE-SZ presented smaller volumes of the left hippocampus, with a significant correlation between left hippocampal volume and verbal memory performance (immediate recall). There was also an inverse correlation between neurochemical ratios (NAA/Cho and Cho/Cr) and verbal memory (delayed recognition). Tests of cognitive flexibility and working memory were not correlated with MRI and 1H MRS values. Compared to HC, FE SZ demonstrated reduced performance in all of the assessed neurocognitive domains. CONCLUSIONS: These results point to a relationship between verbal memory and hippocampal integrity in schizophrenia patients which might be independent from deficits in other memory domains. Disturbed verbal memory functions in FE-SZ might be linked specifically to hippocampal function. PMID- 22047184 TI - Genetics of serum BDNF: meta-analysis of the Val66Met and genome-wide association study. AB - OBJECTIVES: Lower levels of serum brain derived neurotrophic factor (BDNF) is one of the best known biomarkers of depression. To identify genetic variants associated with serum BDNF, we tested the Val66Met (rs6265) functional variant and conducted a genome-wide association scan (GWAS). METHODS: In a community based sample (N = 2054; aged 19-101, M = 51, SD = 15) from Sardinia, Italy, we measured serum BDNF concentration and conducted a GWAS. RESULTS: We estimated the heritability of serum BDNF to be 0.48 from sib-pairs. There was no association between serum BDNF and Val66Met in the SardiNIA sample and in a meta-analysis of published studies (k = 13 studies, total n = 4727, P = 0.92). Although no genome wide significant associations were identified, some evidence of association was found in the BDNF gene (rs11030102, P = 0.001) and at two loci (rs7170215, P = 4.8 * 10-5 and rs11073742 P = 1.2 * 10-5) near and within NTRK3 gene, a neurotrophic tyrosine kinase receptor. CONCLUSIONS: Our study and meta-analysis of the literature indicate that the BDNF Val66Met variant is not associated with serum BDNF, but other variants in the BDNF and NTRK3 genes might regulate the level of serum BDNF. PMID- 22047185 TI - The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment. AB - BACKGROUND: Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. METHODS: 63 cases included antiretroviral treatment naive HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. RESULTS: 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (+/- SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 +/- 1.49 vs. 3.27 +/- 4.95 (p = 0.10), 2.78 +/- 1.60 vs. 3.67 +/- 3.59 (p = 0.08), 3.06 +/- 3.32 vs. 4.04 +/- 2.55 (p = 0.10) respectively and 3.04 MUg/ml (in cases). CONCLUSIONS: Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration. PMID- 22047186 TI - Bioassay-directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents. AB - The widespread occurrence of feminized male fish downstream of some UK Wastewater Treatment Works (WwTWs) has been associated with exposure to estrogenic and potentially antiandrogenic (AA) contaminants in the effluents. In this study, profiling of AA contaminants in WwTW effluents and fish was conducted using HPLC in combination with in vitro androgen receptor transcription screens. Analysis of extracts of wastewater effluents revealed complex profiles of AA activity comprising 21-53 HPLC fractions. Structures of bioavailable antiandrogens were identified by exposing rainbow trout to a WwTW effluent and profiling the bile for AA activity using yeast (anti-YAS) and mammalian-based (AR-CALUX) androgen receptor transcription screens. The predominant fractions with AA activity in both androgen receptor screens contained the germicides chlorophene and triclosan, and together these contaminants accounted for 51% of the total anti YAS activity in the fish bile. Other AA compounds identified in bile included chloroxylenol, dichlorophene, resin acids, napthols, oxybenzone, 4-nonylphenol, and bisphenol A. Pure standards of these compounds were active in the androgen receptor screens at potencies relative to flutamide of between 0.1 and 13.0. Thus, we have identified, for the first time, a diverse range of AA chemicals in WwTWs that are bioavailable to fish and which need to be assessed for their risk to the reproductive health of these organisms and other aquatic biota. PMID- 22047187 TI - Long-term outcome of laparoscopic Nissen procedure in pediatric patients with gastroesophageal reflux disease measured using the modified QPSG Roma III European Society for Pediatric Gastroenterology Hepatology and Nutrition's questionnaire. AB - BACKGROUND/PURPOSE: Laparoscopic fundoplication (LF) represents the gold standard for surgical treatment for pediatric patients with gastroesophageal reflux disease (GERD). METHODS: We report the results of long-term outcome of 36 patients who had undergone LF from January to December 1998, with a follow-up longer than 10 years (range, 11-12 years). The patients were invited, by phone, to undergo a clinical follow-up. All patients underwent the modified European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN)'s Roma III questionnaire; however, only 22 out of 36 patients accepted to be controlled in a day hospital setting, and 10 out of 36 accepted to undergo a telephonic questionnaire. Our study is focused on the data of these 32 patients. RESULTS: Twenty-eight out of 32 (87.5%) patients had completely recovered; 4 out of 32 patients (12.5%) had a mild persistent GER; 9 out of 32 patients (28%) referred a mild dysphagia; 21 out of 32 (66%) patients could burp; and only 9 out of 32 (28%) patients could vomit. The cosmetic result was good in 30 out of 32 (94%) patients. The weight/height ratio was satisfactory in 28 out of 32 (87.5%) patients. The quality of life was good in 28 out of 32 (87.5%) patients. CONCLUSIONS: Our experience shows that the long-term follow-up after LF produces a good clinical result and a good quality of life. The modified ESPGHAN's Roma III questionnaire seems an effective way to check the long-term results, because it avoids submitting patients to long and not well tolerated instrumental exams. PMID- 22047188 TI - Tight and uniform layer of covalently bound aminoethylophenyl groups perpendicular to gold surface for attachment of biomolecules. AB - Strongly adhered layers of the compound with the primary amino group directed toward the solution were obtained at the gold surface by chronoamperometric electroreduction of 4-aminoethylobenzenodiazonium salt (AEBD) in acetonitrile solution at appropriately selected potential. The used techniques (EQCM, AFM, EIS, PM, IRRAS) showed that the nature and thickness of formed aminoethylophenyl layer strongly depend on the potential applied to the electrode. Electroreduction of AEBD salt at a potential more negative than -0.6 V (vs Ag/AgCl) leads to about monolayer on the gold surface. Additionally, such a layer was very tight and uniform. The electrochemical measurements indicate that the efficient and precise attachment of biomolecules to the aminoethylophenyl layer is only possible when this layer is formed at appropriate potential. This was shown for ss- and dsDNA. PMID- 22047189 TI - Erratum. PMID- 22047191 TI - Antimicrobial flavonoids from Tridax procumbens. AB - Callus culture of Tridax procumbens has been established on Murashige and Skoog's medium supplemented with NAA and BAP from nodal segments. Free and bound flavonoids were extracted from 2, 4, 6 and 8 weeks old calli by a well established method. These free flavonoids were then screened against Staphylococcus aureus (bacteria) and Candida albicans (yeast) for their antimicrobial potential. Minimum inhibitory concentration, minimum bactericidal/fungicidal concentrations and total activity were also evaluated. Apigenin, quercetin and kaempferol were identified from free flavonoids of 4 weeks old callus (most active) through, thin layer chromatography, (TLC) preparative TLC, MP and IR spectral studies. PMID- 22047192 TI - Rh-catalyzed ortho-selective C-H borylation of N-functionalized arenes with silica-supported bridgehead monophosphine ligands. AB - Supported phosphine-Rh systems, prepared in situ from silica-supported bridgehead monophosphines and [Rh(OH)(cod)](2), have enabled ortho-selective C-H borylation for a range of arenes containing nitrogen-based directing groups. The regioselectivity was excellent with various N-directing groups, including saturated and unsaturated N-heterocycles, tert-aminoalkyl groups, and imine-type C-N double bonds. The reaction showed significant tolerance toward steric repulsion around the reacting C-H bond. This Rh catalysis complements the Ir catalyzed ortho-borylation, which is effective for arenes with oxygen-based directing groups. PMID- 22047193 TI - Malaria with neurological involvement in Ugandan children: effect on cognitive ability, academic achievement and behaviour. AB - BACKGROUND: Malaria is a leading cause of ill health and neuro-disability in children in sub-Saharan Africa. Impaired cognition is a common outcome of malaria with neurological involvement. There is also a possibility that academic achievement may be affected by malaria with neurological involvement given the association between cognitive ability and academic achievement. This study investigated the effect of malaria with neurological involvement on cognitive ability, behaviour and academic achievement. METHODS: This prospective case control study was carried out in Kampala City, Uganda between February 2008 and October 2010. Sixty-two children with a history of malaria with neurological involvement were followed up and given assessments for cognitive ability (working memory, reasoning, learning, visual spatial skills and attention), behaviour (internalizing and externalizing problems) and academic achievement (arithmetic, spelling and reading) three months after the illness. Sixty-one community controls recruited from the homes or neighbouring families of the cases were also given the same assessments. Tests scores of the two groups were compared using analysis of covariance with age, sex, level of education, nutritional status and quality of the home environment as covariates. This study was approved by the relevant ethical bodies and informed consent sought from the caregivers. RESULTS: Children in the malaria group had more behavioural problems than the community controls for internalizing problems (estimated mean difference = -3.71, 95% confidence interval (CI), = -6.34 to -1.08, p = 0.007). There was marginal evidence of lower attention scores (0.40, CI = -0.05 to 0.86, p = 0.09). However, excluding one child from the analyses who was unable to perform the tests affected the attention scores to borderline significance (0.32, CI, = 0.01 to 0.62, p = 0.05). No significant differences were observed in other cognitive abilities or in academic achievement scores. CONCLUSION: Malaria with neurological involvement affects behaviour, with a minimal effect on attention but no detectable effect on academic achievement at three months post discharge. This study provides evidence that development of cognitive deficits after malaria with neurological involvement could be gradual with less effect observed in the short term compared to the long term. PMID- 22047194 TI - Prospective memory deficits in Ecstasy users: effects of longer ongoing task delay interval. AB - Ecstasy use has been associated with neurotoxicity and neurocognitive impairment in a variety of domains, including prospective memory (ProM), which involves the delayed execution of a previously encoded intention in response to a specific cue. The present study adopted the multiprocess theory of ProM to evaluate the hypothesis that Ecstasy users would evidence differentially impaired ProM on longer versus shorter ongoing task delays. Ecstasy (n = 31) users, high-risk alcohol users (n = 21), and healthy nonusers (n = 31) completed the short (2-min) and long (15-min) delay ProM scales of the Memory for Intentions Screening Test. Results showed a significant group by ProM delay interaction, such that Ecstasy users performed comparably to the comparison groups on short-delay trials, but were impaired on long-delay ProM, particularly for time-based cues. Among the Ecstasy users, long-delay ProM was positively associated with risky decision making, but not with retrospective memory or other aspects of executive functions. These findings suggest that Ecstasy users may be particularly susceptible to deficits in strategic target monitoring and maintenance of cue intention pairings over longer ProM delays. Findings are discussed in the context of their potential everyday functioning (e.g., academic, vocational) and treatment implications for Ecstasy users. PMID- 22047195 TI - Principles of statistics in surgery. AB - Surgery, like any other scientific discipline, requires a systematic analysis of all its different variables in order to prove the real significance of research findings. Statistics, the science of numerical evaluation, can thoroughly help to determine the real value of surgical treatment. In this work, we study the statistical tests and principles needed to demonstrate their role in surgical research. Without a strong statistical background, a researcher may feel overwhelmed when deciding what statistical methods to utilize in research. Determining what type of data to collect and what hypothesis test to run can alter the entire way a surgical study is conducted. The relationship between power, sample size and effect size is discussed as well as the components necessary for a power analysis. Selecting an appropriate sample size is of utmost importance in any type of research since an undersized sample can invalidate an entire study. Categorical surgical data, numerical data, and the appropriate statistical procedures needed for analysis are reviewed. Methods discussed include the 2-Sample t-test, Mann Whitney U test, Kruskal-Wallis, ANOVA, Chi Square test and Fisher's exact test. PMID- 22047196 TI - Advanced imaging technology in surgical innovation. AB - Advanced imaging technologies including computed tomography (CT) and magnetic resonance imaging (MRI) have immensely expanded possibilities in imaging and surgery. The accurate visualization of bones and soft tissue has transformed the surgical management of numerous diseases, including middle ear disease, orthopedic and reconstructive cases, and cancer. In fact, in surgical subspecialties such as neurosurgery, CT and MRI are the diagnostic modalities of choice for preoperative evaluation of patients. Furthermore, the ongoing development of the newer imaging technologies continues to expand image-guided surgical treatments. The development of new radiological modalities combined with the modern training of surgeons will provide an exciting landscape for future practicing physicians. PMID- 22047197 TI - Magnesium sulfate does not protect spinal cord against ischemic injury. AB - OBJECTIVE: We tested various doses of MgSO(4) to investigate the effect of Mg on a spinal cord ischemia. METHODS: Rats were treated with either MgSO(4) (30, 100, or 300 mg/kg; group Mg(low), group Mg(medium), group Mg(high), respectively, n = 10 for each) or saline (control group; n = 10) before ischemia. Spinal cord ischemia was induced using a balloon-tipped catheter placed on proximal descending aorta. During surgery, hemodynamic variables were recorded before ischemia, during aortic occlusion and after reperfusion. Neurologic function was assessed using the motor deficit index (MDI; 0 = normal, 6 = complete paralysis) until seven days after reperfusion, and histologic examination of spinal cord was performed. RESULTS: After reperfusion, the mean arterial pressure in the group Mg(high) was significantly lower than other groups. Compared to the control group, the groups Mg(low) and Mg(medium) did not show any difference in MDI and the group Mg(high) showed significantly higher MDI. The number of normal motor neurons was similar among other groups except the group Mg(high) had a significantly fewer normal motor neurons. CONCLUSIONS: Intravenous MgSO(4) with low or medium dose (30, or 100 mg/kg) did not improve neurological injury following spinal cord ischemia. Furthermore, higher dose of MgSO(4) (300 mg/kg) resulted in hemodynamic instability and aggravated neurologic outcome. PMID- 22047198 TI - Platelet-rich plasma application and heterotopic bone formation following total hip arthroplasty. AB - Activated blood platelets play a critical, early role in the wound healing response by releasing several types of growth factors at the site of injury which mediate the initial stages of tissue repair. Autologously derived platelet-rich plasma has been applied during surgery as a healing aid and some studies have shown benefit with total joint arthroplasty procedures such as in the knee. However, little has been published regarding the use of platelet-rich plasma during total hip arthroplasty. The hip is especially prone to develop islands of heterotopic bone following arthroplasty which can lead to pain, limited motion, and even ankylosis of the joint. If this condition is exacerbated by platelet rich plasma, this could present a barrier to the use of this adjuvant in total hip arthroplasty. This retrospective, controlled clinical study examined the effect of platelet rich plasma application during closure following total hip arthroplasty on heterotopic ossification. By one year, 21.3% of the control patients developed heterotopic bone (91 patients, 94 hips, Brooker grades I-III) compared to 12.9% of the treatment patients (76 patients, 85 hips, Brooker grades I-II). These differences were not significant (p = 0.478, power = 0.90). Thus, the use of platelet-rich plasma in this procedure does not appear to influence the incidence or severity of heterotopic ossification which should help to justify further clinical research to more fully understand whether this autologous blood product has a role in total hip arthroplasty. PMID- 22047199 TI - Two-day fasting prior to intestinal ischemia-reperfusion injury on bacterial translocation in rats. AB - PURPOSE: The aim of this study is to verify the effect of two-day fasting prior to intestinal ischemia-reperfusion (I/R) injury on bacterial translocation (BT). MATERIALS AND METHODS: Mail Sprague-Dawley rats were divided into four groups: group 1, control rats that underwent sham operation only; group 2, rats fasted for two days prior to sham operation; group 3, rats that underwent occlusion of mesenteric vessels for 30 min followed by reperfusion for 4 hr; and group 4, rats fasted for two days prior to the same intestinal I/R injury as in group 3. In all groups, E. coli labeled with (99m)Tc were inoculated into the terminal ileum. Two hr after inoculation of E. coli, the rats were killed. A segment of ileum was obtained for histological examination and samples of mesenteric lymph nodes (MLNs), liver, lung, blood, and spleen were obtained for radioactivity determination. RESULTS: There were no significant differences in the intestinal mucosa and radioactivity of all samples between groups 1 and 2. Group 3 showed significantly shorter mucosa and villi, and higher radioactivity of samples, except for MLNs, compared to group 1. Group 4 showed similar mucosa and villi, but significantly higher radioactivity of samples, except for MLNs, compared to group 3. CONCLUSION: Two-day fasting without I/R injury does not cause mucosal change and BT, but in cases following intestinal I/R injury, two-day fasting increases the susceptibility of BT to systemic organs in rats. PMID- 22047200 TI - Type of steatosis influences microcirculation and fibrogenesis in different rat strains. AB - This study investigates the impact of rat strain on the development of nonalcoholic fatty liver disease (NAFLD) focusing on morphological features and microcirculation. Male rats of Lewis, Wistar, and Sprague Dawley (n = 6 per strain and group) were randomized into a high-fat group which was fed with a special high-fat nutrition for a 3-week period and a control group which received standard nutrition. Intravital microscopy was used for the evaluation of microcirculation and correlated to morphological changes using a fatty liver scoring system. All three strains receiving a high-fat diet developed a grade 3 steatosis (>66% liver cell steatosis). Whereas Lewis showed a solely microvesicular steatosis, Wistar developed a mixed form and Sprague Dawley showed a pure macrovesicular steatosis and the highest degree of fibrosis and hepatocyte damage. Microcirculatory results revealed that sinusoidal density was already affected by a microvesicular steatosis and decreased with increasing macrovesicular proportion (Lewis: 18%, Wistar: 31%, Sprague Dawley: 23%). The degree of steatosis correlates with reduced blood flow velocity in central veins as well as in sinusoids (Lewis: 28%, Wistar: 39%, Sprague Dawley 44%). The densities of hepatocytes and hepatic stellate cells were only impaired once macrovesicular cell steatosis (Wistar and Sprague Dawley) was present. The development of NAFLD in the rat revealed strain-specific morphological features correlating with microcirculatory changes that should be considered in further studies using these models. PMID- 22047201 TI - The effects of testosterone on intestinal ischemia/reperfusion in rats. AB - ABSTRACT Ischemic injury to the gut is believed to occur in many serious clinical conditions. Our aim was to investigate the postischemia/reperfusion (I/R) effects of exogenously administered testosterone on the intestines of normal and orchiectomized rats.Forty-eight rats were divided into eight groups of six animals: (1) Sham-operated control group; (2) Sham-operated + testosterone treated group; (3) I/R group: Rats were subjected to the surgical procedures and underwent intestinal ischemia for 60 min followed by reperfusion for 60 min; (4) I/R + testosterone-treated group: Rats were subjected to the surgical procedures and received testosterone 100 mg/kg (i.p.); (5) I/R + orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (6) orchiectomy group: Rats were subjected to the surgical procedures as well as orchiectomy; (7) orchiectomy + testosterone-treated group: Rats were subjected to the surgical procedures as well as orchiectomy and received testosterone 100 mg/kg (i.p.); and (8) I/R + orchiectomy + testosterone-treated group. The histological findings of this study paralleled the observed degree of lipid peroxidation (LPO) and protein oxidation. Intestinal mucosal injury was extensive in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups, but was less in the I/R + testosterone group. Histopathological injury also paralleled the degree of oxidative stress. Apoptotic enterocytes were more numerous in the I/R, I/R + orchiectomy, and I/R + orchiectomy + testosterone groups. Administration of testosterone in the presence of testes significantly protected intestinal tissue against I/R mucosal injuries, while administration of testosterone in the absence of testes did not significantly protect intestinal tissue against I/R mucosal injuries. PMID- 22047202 TI - Comparison of long-term biocompability of PVDF and PP meshes. AB - BACKGROUND: Abdominal hernia repair is the most frequently performed operation in surgery. Mesh repair in hernia surgery has become an integral component. Although meshes made of PVDF are already in clinical use, so far no data of long-term biocompability are available. METHODS: In this study a PVDF mesh was compared to a polypropylene mesh with regard to its long-term biocompatibility. A total of 28 rats were randomized to two groups. Mesh material was implanted subcutaneously; animals were euthanized seven days and six months postoperatively. The quantity of inflammatory tissue response was characterized by measuring the diameter of the foreign body granuloma. Furthermore quality of cellular immune response (T lymphocytes, macrophages, and neutrophils), and inflammation (COX-2) was analyzed by immunohistochemistry. Furthermore the collagen type I/III ratio was determined. RESULTS: Macrophages, T-lymphocytes, neutrophiles, and COX-2 declined significantly up to six months postoperatively in comparison to day 7 for both PVDF and PP meshes, and in both groups the collagen ratio increased significantly in the course of time. PVDF meshes showed a foreign body granuloma size significantly reduced compared to PP (7 days: 20 +/- 2 MUm vs. 27 +/- 2 MUm; 6 months 15 +/- 2 MUm vs. 22 +/- 3 MUm; p < .001). However no significant differences were found analyzing cellular response six months postoperatively. CONCLUSIONS: Our current data suggest that even in the long-term course after six months and despite a higher effective surface of the PVDF samples it showed a smaller foreign body granuloma than with PP whereas the cellular response was similar. PMID- 22047203 TI - Collagen implants in hernia repair. PMID- 22047206 TI - Shotgun proteomic analysis of long-distance drought signaling in rice roots. AB - Rice (Oryza sativa L. cv. IR64) was grown in split-root systems to analyze long distance drought signaling within root systems. This in turn underpins how root systems in heterogeneous soils adapt to drought. The approach was to compare four root tissues: (1) fully watered; (2) fully droughted and split-root systems where (3) one-half was watered and (4) the other half was droughted. This was specifically aimed at identifying how droughted root tissues altered the proteome of adjacent wet roots by hormone signals and how wet roots reciprocally affected dry roots hydraulically. Quantitative label-free shotgun proteomic analysis of four different root tissues resulted in identification of 1487 nonredundant proteins, with nearly 900 proteins present in triplicate in each treatment. Drought caused surprising changes in expression, most notably in partially droughted roots where 38% of proteins were altered in level compared to adjacent watered roots. Specific functional groups changed consistently in drought. Pathogenesis-related proteins were generally up-regulated in response to drought and heat-shock proteins were totally absent in roots of fully watered plants. Proteins involved in transport and oxidation-reduction reactions were also highly dependent upon drought signals, with the former largely absent in roots receiving a drought signal while oxidation-reduction proteins were strongly present during drought. Finally, two functionally contrasting protein families were compared to validate our approach, showing that nine tubulins were strongly reduced in droughted roots while six chitinases were up-regulated, even when the signal arrived remotely from adjacent droughted roots. PMID- 22047207 TI - Dispersal state of multiwalled carbon nanotubes elicits profibrogenic cellular responses that correlate with fibrogenesis biomarkers and fibrosis in the murine lung. AB - We developed a dispersal method for multiwalled carbon nanotubes (MWCNTs) that allows quantitative assessment of dispersion on profibrogenic responses in tissue culture cells and in mouse lung. We demonstrate that the dispersal of as-prepared (AP), purified (PD), and carboxylated (COOH) MWCNTs by bovine serum albumin (BSA) and dipalmitoylphosphatidylcholine (DPPC) influences TGF-beta1, PDGF-AA, and IL 1beta production in vitro and in vivo. These biomarkers were chosen based on their synergy in promoting fibrogenesis and cellular communication in the epithelial-mesenchymal cell trophic unit in the lung. The effect of dispersal was most noticeable in AP- and PD-MWCNTs, which are more hydrophobic and unstable in aqueous buffers than hydrophilic COOH-MWCNTs. Well-dispersed AP- and PD-MWCNTs were readily taken up by BEAS-2B, THP-1 cells, and alveolar macrophages (AM) and induced more prominent TGF-beta1 and IL-1beta production in vitro and TGF-beta1, IL-1beta, and PDGF-AA production in vivo than nondispersed tubes. Moreover, there was good agreement between the profibrogenic responses in vitro and in vivo as well as the ability of dispersed tubes to generate granulomatous inflammation and fibrosis in airways. Tube dispersal also elicited more robust IL-1beta production in THP-1 cells. While COOH-MWCNTs were poorly taken up in BEAS-2B and induced little TGF-beta1 production, they were bioprocessed by AM and induced less prominent collagen deposition at sites of nongranulomatous inflammation in the alveolar region. Taken together, these results indicate that the dispersal state of MWCNTs affects profibrogenic cellular responses that correlate with the extent of pulmonary fibrosis and are of potential use to predict pulmonary toxicity. PMID- 22047208 TI - Solid-phase synthesis of mimosine tetrapeptides and their inhibitory activities on neuraminidase and tyrosinase. AB - Neuraminidase is a rational target for influenza inhibition, and the search for neuraminidase inhibitors has been intensified. Mimosine, a nonprotein amino acid, was for the first time identified as a neuraminidase inhibitor with an IC(50) of 9.8 +/- 0.2 MUM. It was found that mimosine had slow, time-dependent competitive inhibition against the neuraminidase. Furthermore, a small library of mimosine tetrapeptides (M-A(1)-A(2)-A(3)) was synthesized by solid-phase synthesis and was assayed to evaluate their neuraminidase and tyrosinase inhibitory properties. Most of the tetrapeptides showed better activities than mimosine. Mimosine-FFY was the best compound, and it exhibited 50% neuraminidase inhibition at a low micromolar range of 1.8 +/- 0.2 MUM, whereas for tyrosinase inhibition, it had an IC(50) of 18.3 +/- 0.5 MUM. The kinetic studies showed that all of the synthesized peptides inhibited neuraminidase noncompetitively with K(i) values ranging from 1.9 -to 7.2 MUM. These results suggest that mimosine could be used as a source of bioactive compounds and may have possibilities in the design of drugs as neuraminidase and tyrosinase inhibitors. PMID- 22047210 TI - Phosphonic acid functionalized asymmetric phthalocyanines: synthesis, modification of indium tin oxide, and charge transfer. AB - Metalated and free-base A(3)B-type asymmetric phthalocyanines (Pcs) bearing, in the asymmetric quadrant, a flexible alkyl linker of varying chain lengths terminating in a phosphonic acid (PA) group have been synthesized. Two parallel series of asymmetric Pc derivatives bearing aryloxy and arylthio substituents are reported, and their synthesis and characterization through NMR, combustion analysis, and MALDI-MS are described. We also demonstrate the modification of indium tin oxide (ITO) substrates using the PA functionalized asymmetric Pc derivatives and monitoring their electrochemistry. The PA functionalized asymmetric Pcs were anchored to the ITO surface through chemisorption and their electrochemical properties characterized using cyclic voltammetry to investigate the effects of PA structure on the thermodynamics and kinetics of charge transfer. Ionization energies of the modified ITO surfaces were measured using ultraviolet photoemission spectroscopy. PMID- 22047209 TI - The association between parity, infant gender, higher level of paternal education and preterm birth in Pakistan: a cohort study. AB - BACKGROUND: High rates of antenatal depression and preterm birth have been reported in Pakistan. Self reported maternal stress and depression have been associated with preterm birth; however findings are inconsistent. Cortisol is a biological marker of stress and depression, and its measurement may assist in understanding the influence of self reported maternal stress and depression on preterm birth. METHODS: In a prospective cohort study pregnant women between 28 to 30 weeks of gestation from the Aga Khan Hospital for Women and Children completed the A-Z Stress Scale and the Centre for Epidemiology Studies Depression Scale to assess stress and depression respectively, and had a blood cortisol level drawn. Women were followed up after delivery to determine birth outcomes. Correlation coefficients and Wilcoxon rank sum test was used to assess relationship between preterm birth, stress, depression and cortisol. Logistic regression analysis was used to determine the key factors predictive of preterm birth. RESULTS: 132 pregnant women participated of whom 125 pregnant women had both questionnaire and cortisol level data and an additional seven had questionnaire data only. Almost 20% of pregnant women (19.7%, 95% CI 13.3-27.5) experienced a high level of stress and nearly twice as many (40.9%, 95% CI 32.4 49.8%) experienced depressive symptoms. The median of cortisol level was 27.40 ug/dl (IQR 22.5-34.2). The preterm birth rate was 11.4% (95% CI 6.5-18). There was no relationship between cortisol values and stress scale or depression. There was a significant positive relationship between maternal depression and stress. Preterm birth was associated with higher parity, past delivery of a male infant, and higher levels of paternal education. Insufficient numbers of preterm births were available to warrant the development of a multivariable logistic regression model. CONCLUSIONS: Preterm birth was associated with higher parity, past delivery of a male infant, and higher levels of paternal education. There was no relationship between stress, and depression, cortisol and preterm birth. There were high rates of stress and depression among this sample suggesting that there are missed opportunities to address mental health needs in the prenatal period. Improved methods of measurement are required to better understand the psychobiological basis of preterm birth. PMID- 22047211 TI - Questionnaire of chronic illness care in primary care-psychometric properties and test-retest reliability. AB - BACKGROUND: The Chronic Care Model (CCM) is an evidence-based approach to improving the structure of care for chronically ill patients with multimorbidity. The Assessment of Chronic Illness Care (ACIC), an instrument commonly used in international research, includes all aspects of the CCM, but cannot be easily extended to the German context. A new instrument called the "Questionnaire of Chronic Illness Care in Primary Care" (QCPC) was developed for use in Germany for this reason. Here, we present the results of the psychometric properties and test retest reliability of QCPC. METHODS: A total of 109 family doctors from different German states participated in the validation study. Participating physicians completed the QCPC, which includes items concerning the CCM and practice structure, at baseline (T0) and 3 weeks later (T1). Internal consistency reliability and test-retest reliability were evaluated using Cronbach's alpha and Pearson's r, respectively. RESULTS: The QCPC contains five elements of the CCM (decision support, delivery system design, self-management support, clinical information systems, and community linkages). All subscales demonstrated moderate internal consistency and moderate test-retest reliability over a three-week interval. CONCLUSIONS: The QCPC is an appropriate instrument to assess the structure of chronic illness care. Unlike the ACIC, the QCPC can be used by health care providers without CCM training. The QCPC can detect the actual state of care as well as areas for improvement of care according to the CCM. PMID- 22047212 TI - Quantum chemistry study on internal conversion of diphenyldibenzofulvene in solid phase. AB - We investigate the nonradiative decay process of diphenyldibenzofulvene (DPDBF) in solid phase by using the quantum chemistry methods. To carry out the nonradiative rate constant calculation, we construct a solid phase model based on the ONIOM method. The geometry of the DPDBF molecule is optimized for the ground state by DFT and the first excited state by TD-DFT, and the corresponding vibrational frequencies and normal coordinates are computed. Under displaced distorted harmonic oscillator potential approximation, Huang-Rhys factors are obtained. Vibronic coupling constants are calculated as a function of the normal mode based on Domcke's scheme. We find that vibronic coupling constants of 12 modes with large reorganization energies are of similar order, and if this result is still valid for other modes, the internal conversion rate would be determined by high frequency modes because they have a significant nuclear factor that is related to Franck-Condon overlap intergrals. We also find that geometrical changes are suppressed due to the stacking effect, which yields small Huang-Rhys values in the solid phase. PMID- 22047217 TI - ERRATUM. PMID- 22047218 TI - A transformative perspective on learning and professional development of Afghan physiotherapists. AB - The aim of this article is to explore factors that impacted learning of Afghan physiotherapists in a development project to improve the physiotherapy services in a disability programme implemented by a Swedish nongovernmental organisation in Afghanistan. Participant observation, recorded as field notes, was used to document the process, to gain a better understanding of professional development of physiotherapists in Afghanistan. Field notes were analysed and factors affecting learning were interpreted from a perspective inspired by transformative learning. Various factors were identified: a pattern approach to treatment, linear thinking, and socially oriented decision making affected how new things learned were put into practice; concrete representations and an instrumental view of knowledge characterised learning approaches; language barriers, different interpretations of meaning, and cultural codes challenged communication; and a prescriptive, encouraging approach of the expatriate physiotherapy development worker affected teaching and learning. Working with professional development across cultural borders is challenging, and the identified factors impacting learning can help expatriate physiotherapists in adapting training to the Afghan context. Exploring meaning perspectives and communicative learning could enhance understanding of these factors for both expatriate and Afghan physiotherapists and should be a focus in future development activities. PMID- 22047220 TI - Correlation between Fischer-Tropsch catalytic activity and composition of catalysts. AB - This paper presents the synthesis and characterization of monometallic and bimetallic cobalt and iron nanoparticles supported on alumina. The catalysts were prepared by a wet impregnation method. Samples were characterized using temperature-programmed reduction (TPR), temperature-programmed oxidation (TPO), CO-chemisorption, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM-EDX) and N2-adsorption analysis. Fischer-Tropsch synthesis (FTS) was carried out in a fixed-bed microreactor at 543 K and 1 atm, with H2/CO = 2 v/v and space velocity, SV = 12L/g.h. The physicochemical properties and the FTS activity of the bimetallic catalysts were analyzed and compared with those of monometallic cobalt and iron catalysts at similar operating conditions.H2-TPR analysis of cobalt catalyst indicated three temperature regions at 506 degrees C (low), 650 degrees C (medium) and 731 degrees C (high). The incorporation of iron up to 30% into cobalt catalysts increased the reduction, CO chemisorption and number of cobalt active sites of the catalyst while an opposite trend was observed for the iron-riched bimetallic catalysts. The CO conversion was 6.3% and 4.6%, over the monometallic cobalt and iron catalysts, respectively. Bimetallic catalysts enhanced the CO conversion. Amongst the catalysts studied, bimetallic catalyst with the composition of 70Co30Fe showed the highest CO conversion (8.1%) while exhibiting the same product selectivity as that of monometallic Co catalyst. Monometallic iron catalyst showed the lowest selectivity for C5+ hydrocarbons (1.6%). PMID- 22047221 TI - Communication: A dynamical theory of homogeneous nucleation for colloids and macromolecules. AB - Homogeneous nucleation is formulated within the context of fluctuating hydrodynamics. It is shown that for a colloidal system in the strong damping limit the most likely path for nucleation can be determined by gradient descent in density space governed by a nontrivial metric. This is illustrated by application to low-density/high-density liquid transition of globular proteins in solution where it is shown that nucleation process involves two stages: the formation of an extended region with enhanced density followed by the formation of a cluster within this region. PMID- 22047222 TI - On the gauge invariance of nonperturbative electronic dynamics using the time dependent Hartree-Fock and time-dependent Kohn-Sham. AB - Nonperturbative electronic dynamics using the time-dependent Hartree-Fock (TDHF) and time-dependent Kohn-Sham (TDKS) theories with the adiabatic approximation is a powerful tool in obtaining insights into the interaction between a many electron system and an external electromagnetic field. In practical applications of TDHF/TDKS using a truncated basis set, the electronic dynamics and molecular properties become gauge-dependent. Numerical simulations are carried out in the length gauge and velocity gauge to verify the extent of gauge-dependence using incomplete basis sets. Electronic dynamics of two many-electron systems, a helium atom and a carbon monoxide molecule in high-intensity linearly polarized radiation fields are performed using the TDHF and TDKS with two selected adiabatic exchange-correlation (xc) functionals. The time evolution of the expectation values of the dipole moment and harmonic spectra are calculated in the two gauges, and the basis set dependence on the gauge-invariance of these properties is investigated. PMID- 22047223 TI - Relaxation mode analysis of a peptide system: comparison with principal component analysis. AB - This article reports the first attempt to apply the relaxation mode analysis method to a simulation of a biomolecular system. In biomolecular systems, the principal component analysis is a well-known method for analyzing the static properties of fluctuations of structures obtained by a simulation and classifying the structures into some groups. On the other hand, the relaxation mode analysis has been used to analyze the dynamic properties of homopolymer systems. In this article, a long Monte Carlo simulation of Met-enkephalin in gas phase has been performed. The results are analyzed by the principal component analysis and relaxation mode analysis methods. We compare the results of both methods and show the effectiveness of the relaxation mode analysis. PMID- 22047224 TI - Chemical reactions modulated by mechanical stress: extended Bell theory. AB - A number of recent studies have shown that mechanical stress can significantly lower or raise the activation barrier of a chemical reaction. Within a common approximation due to Bell [Science 200, 618 (1978)], this barrier is linearly dependent on the applied force. A simple extension of Bell's theory that includes higher order corrections in the force predicts that the force-induced change in the activation energy will be given by -FDeltaR - DeltachiF(2)/2. Here, DeltaR is the change of the distance between the atoms, at which the force F is applied, from the reactant to the transition state, and Deltachi is the corresponding change in the mechanical compliance of the molecule. Application of this formula to the electrocyclic ring-opening of cis and trans 1,2-dimethylbenzocyclobutene shows that this extension of Bell's theory essentially recovers the force dependence of the barrier, while the original Bell formula exhibits significant errors. Because the extended Bell theory avoids explicit inclusion of the mechanical stress or strain in electronic structure calculations, it allows a computationally efficient characterization of the effect of mechanical forces on chemical processes. That is, the mechanical susceptibility of any reaction pathway is described in terms of two parameters, DeltaR and Deltachi, both readily computable at zero force. PMID- 22047225 TI - Short-time self-diffusion coefficient of a particle in a colloidal suspension bounded by a microchannel: virial expansions and simulation. AB - Self-diffusion of colloidal particles confined to a cylindrical microchannel is considered theoretically and numerically. Virial expansion of the self-diffusion coefficient is performed. Two-body and three-body hydrodynamic interactions are evaluated with high precision using the multipole method. The multipole expansion algorithm is also used to perform numerical simulations of the self-diffusion coefficient, valid for all possible particle packing fractions. Comparison with earlier results shows that the widely used method of reflections is insufficient for calculations of hydrodynamic interactions even for small packing fractions and small particles radii, contrary to the prevalent opinion. PMID- 22047226 TI - Assessing weak hydrogen binding on Ca+ centers: an accurate many-body study with large basis sets. AB - Weak H(2) physisorption energies present a significant challenge to even the best correlated theoretical many-body methods. We use the phaseless auxiliary-field quantum Monte Carlo method to accurately predict the binding energy of Ca(+) 4H(2). Attention has recently focused on this model chemistry to test the reliability of electronic structure methods for H(2) binding on dispersed alkaline earth metal centers. A modified Cholesky decomposition is implemented to realize the Hubbard-Stratonovich transformation efficiently with large Gaussian basis sets. We employ the largest correlation-consistent Gaussian type basis sets available, up to cc-pCV5Z for Ca, to accurately extrapolate to the complete basis limit. The calculated potential energy curve exhibits binding with a double-well structure. PMID- 22047227 TI - Non-equilibrium spin-boson model: counting statistics and the heat exchange fluctuation theorem. AB - We focus on the non-equilibrium two-bath spin-boson model, a toy model for examining quantum thermal transport in many-body open systems. Describing the dynamics within the noninteracting-blip approximation equations, applicable, e.g., in the strong system-bath coupling limit and/or at high temperatures, we derive expressions for the cumulant generating function in both the Markovian and non-Markovian limits by energy-resolving the quantum master equation of the subsystem. For a Markovian bath, we readily demonstrate the validity of a steady state heat exchange fluctuation theorem. In the non-Markovian limit a "weaker" symmetry relation generally holds, a general outcome of microreversibility. We discuss the reduction of this symmetry relation to the universal steady-state fluctuation theorem. Using the cumulant generating function, an analytic expression for the heat current is obtained. Our results establish the validity of the steady-state heat exchange fluctuation theorem in quantum systems with strong system-bath interactions. From the practical point of view, this study provides tools for exploring transport characteristics of the two-bath spin-boson model, a prototype for a nonlinear thermal conductor. PMID- 22047228 TI - Optimized hierarchical equations of motion theory for Drude dissipation and efficient implementation to nonlinear spectroscopies. AB - Hierarchical equations of motion theory for Drude dissipation is optimized, with a convenient convergence criterion proposed in advance of numerical propagations. The theoretical construction is on the basis of a Pade spectrum decomposition that has been qualified to be the best sum-over-poles scheme for quantum distribution function. The resulting hierarchical dynamics under the a priori convergence criterion are exemplified with a benchmark spin-boson system, and also the transient absorption and related coherent two-dimensional spectroscopy of a model exciton dimer system. We combine the present theory with several advanced techniques such as the block hierarchical dynamics in mixed Heisenberg Schrodinger picture and the on-the-fly filtering algorithm for the efficient evaluation of third-order optical response functions. PMID- 22047229 TI - Ab initio properties of Li-group-II molecules for ultracold matter studies. AB - We perform a systematic investigation of the electronic properties of the (2)Sigma(+) ground state of Li-alkaline-earth dimers. These molecules are proposed as possible candidates for quantum simulation of lattice-spin models. We apply powerful quantum chemistry coupled-cluster method and large basis sets to calculate potential energies and permanent dipole moments for the LiBe, LiMg, LiCa, LiSr, and LiYb molecules. Agreement of calculated molecular constants with existing experimental data is better than or equal to 8%. Our results reveal a surprising irregularity in the dissociation energy and bond length with an increase in the reduced mass of the molecule. At the same time, the permanent dipole moment at the equilibrium separation has the smallest value between 0.01 a.u. and 0.1 a.u. for the heaviest (LiSr and LiYb) molecules and increases to 1.4 a.u. for the lightest (LiBe), where 1 a.u. is one atomic unit of dipole moment. We consider our study of the (2)Sigma(+) molecules a first step towards a comprehensive analysis of their interactions in an optical trap. PMID- 22047230 TI - Geometry optimization of bimetallic clusters using an efficient heuristic method. AB - In this paper, an efficient heuristic algorithm for geometry optimization of bimetallic clusters is proposed. The algorithm is mainly composed of three ingredients: the monotonic basin-hopping method with guided perturbation (MBH GP), surface optimization method, and iterated local search (ILS) method, where MBH-GP and surface optimization method are used to optimize the geometric structure of a cluster, and the ILS method is used to search the optimal homotop for a fixed geometric structure. The proposed method is applied to Cu(38-n)Au(n) (0 <= n <= 38), Ag(55-n)Au(n) (0 <= n <= 55), and Cu(55-n)Au(n) (0 <= n <= 55) clusters modeled by the many-body Gupta potential. Comparison with the results reported in the literature indicates that the present method is highly efficient and a number of new putative global minima missed in the previous papers are found. The present method should be a promising tool for the theoretical determination of ground-state structure of bimetallic clusters. Additionally, some key elements and properties of the present method are also analyzed. PMID- 22047231 TI - Dispersion, static correlation, and delocalisation errors in density functional theory: an electrostatic theorem perspective. AB - Dispersion, static correlation, and delocalisation errors in density functional theory are considered from the unconventional perspective of the force on a nucleus in a stretched diatomic molecule. The electrostatic theorem of Feynman is used to relate errors in the forces to errors in the electron density distortions, which in turn are related to erroneous terms in the Kohn-Sham equations. For H(2), the exact dispersion force arises from a subtle density distortion; the static correlation error leads to an overestimated force due to an exaggerated distortion. For H(2)(+), the exact force arises from a delicate balance between attractive and repulsive components; the delocalisation error leads to an underestimated force due to an underestimated distortion. The net force in H(2)(+) can become repulsive, giving the characteristic barrier in the potential energy curve. Increasing the fraction of long-range exact orbital exchange increases the distortion, reducing delocalisation error but increasing static correlation error. PMID- 22047232 TI - Extended Lagrangian free energy molecular dynamics. AB - Extended free energy Lagrangians are proposed for first principles molecular dynamics simulations at finite electronic temperatures for plane-wave pseudopotential and local orbital density matrix-based calculations. Thanks to the extended Lagrangian description, the electronic degrees of freedom can be integrated by stable geometric schemes that conserve the free energy. For the local orbital representations both the nuclear and electronic forces have simple and numerically efficient expressions that are well suited for reduced complexity calculations. A rapidly converging recursive Fermi operator expansion method that does not require the calculation of eigenvalues and eigenfunctions for the construction of the fractionally occupied density matrix is discussed. An efficient expression for the Pulay force that is valid also for density matrices with fractional occupation occurring at finite electronic temperatures is also demonstrated. PMID- 22047233 TI - Solvation effects on angular distributions in H- (NH3)n and NH2(-) (NH3)n photodetachment: role of solute electronic structure. AB - We report 355 and 532 nm photoelectron imaging results for H(-)(NH(3))(n) and NH(2)(-)(NH(3))(n), n = 0-5. The photoelectron spectra are consistent with the electrostatic picture of a charged solute (H(-) or NH(2)(-)) solvated by n ammonia molecules. For a given number of solvent molecules, the NH(2)(-) core anion is stabilized more strongly than H(-), yet the photoelectron angular distributions for solvated H(-) deviate more strongly from the unsolvated limit than those for solvated NH(2)(-). Hence, we conclude that solvation effects on photoelectron angular distributions are dependent on the electronic structure of the anion, i.e., the type of the initial orbital of the photodetached electron, rather than merely the strength of solvation interactions. We also find evidence of photofragmentation and autodetachment of NH(2)(-)(NH(3))(2-5), as well as autodetachment of H(-)(NH(3))(5), upon 532 nm excitation of these species. PMID- 22047234 TI - Photoelectron angular distributions in negative-ion photodetachment from mixed sp states. AB - We describe an approach for constructing analytical models for the energy dependence of photoelectron angular distributions in the one-electron, non relativistic approximation. We construct such a model for electron emission from an orbital described as a superposition of s- and p-type functions, using linearly polarized light. In the limits of pure s or pure p electron photodetachment or photoionization, the model correctly reproduces the familiar Cooper-Zare formula. The model predictions are compared to experimental results for strongly solvated H(-) and NH(2)(-), corresponding to predominantly s and predominantly p character parent states, respectively. PMID- 22047235 TI - A theoretical study of hydrogen- and lithium-bonded complexes of F-H/Li and Cl H/Li with NF3, NH3, and NH2(CH3). AB - Hydrogen- and lithium-bonded complexes of A-H/Li (A = F, Cl) with the amine analogues NF(3), NH(3), and NH(2)(CH(3)) were studied at the MP2/6-311++G(d,p) level of theory. Bond extensions and redshifts were obtained for the H-bonded complexes, while bond extensions and blueshifts were obtained for the Li-bonded species. The variation of these and other properties with the basicity of the amines was investigated and rationalized by comparing the ab initio results with predictions from a model derived from perturbation theory. PMID- 22047236 TI - Control of vibronic excitation using quantum-correlated photons. AB - We theoretically investigate the two-step excitation of a molecular vibronic state using quantum-correlated photons with time delay in order to control the population of the vibronic excited state. A Morse oscillator having three sets of vibronic states, namely, the ground state, intermediate states, and excited states, is used to evaluate the efficiency of the two-step excitation process. We show that we can efficiently and selectively excite only a target state by using correlated photons and can control the excitation population of the target state by adjusting the delay time of the correlated photons. The potential of controlling a chemical reaction using correlated photons is also discussed. PMID- 22047237 TI - Ab initio quantum dynamical study of photoinduced ring opening in furan. AB - The nonadiabatic photoinduced ring opening occurring in the two lowest excited singlet states of furan is investigated theoretically, using wave-packet propagation techniques. The underlying multidimensional potential energy surfaces (PESs) are obtained from ab initio computations, using the equation-of-motion coupled cluster method restricted to single and double excitations (EOM-CCSD), reported in earlier recent work [E. V. Gromov, A. B. Trofimov, F. Gatti, and H. Koppel, J. Chem. Phys. 133, 164309 (2010)]. Up to five nuclear degrees of freedom are considered in the quantum dynamical treatment. Four of them represent in plane motion for which the electronic states in question (correlating with the valence (1)B(2)(V) and Rydberg (1)A(2)(3s) states at the C(2v) ground-state molecular configuration) have different symmetries, A(') and A(''), respectively. The fifth mode, representing out-of-plane bending of the oxygen atom against the carbon-atom plane, leads to an interaction of these states, as is crucial for the photoreaction. The nonadiabatic coupling and conical intersection cause an electronic population transfer on the order of ~10 fs. Its main features, and that of the wave-packet motion, are interpreted in terms of properties of the PES. The lifetime due to the ring-opening process has been estimated to be around 2 ps. The dependence of this estimate on the nuclear degrees of freedom retained in the computations is discussed. PMID- 22047238 TI - Theoretical investigation of the photophysics of methyl salicylate isomers. AB - The photophysics of methyl salicylate (MS) isomers has been studied using time dependent density functional theory and large basis sets. First electronic singlet and triplet excited states energies, structure, and vibrational analysis were calculated for the ketoB, enol, and ketoA isomers. It is demonstrated that the photochemical pathway involving excited state intramolecular proton transfer (ESIPT) from the ketoB to the enol tautomer agrees well with the dual fluorescence in near-UV (from ketoB) and blue (from enol) wavelengths obtained from experiments. Our calculation confirms the existence of a double minimum in the excited state pathway along the O-H-O coordinate corresponding to two preferred energy regions: (1) the hydrogen belongs to the OH moiety and the structure of methyl salicylate is ketoB; (2) the hydrogen flips to the closest carboxyl entailing electronic rearrangement and tautomerization to the enol structure. This double well in the excited state is highly asymmetric. The Franck Condon vibrational overlap is calculated and accounts for the broadening of the two bands. It is suggested that forward and backward ESIPT through the barrier separating the two minima is temperature-dependent and affects the intensity of the fluorescence as seen in experiments. When the enol fluoresces and returns to its ground state, a barrier-less back proton transfer repopulates the ground state of methyl salicylate ketoB. It is also demonstrated that the rotamer ketoA is not stable in an excited state close to the desired emission wavelength. This observation eliminates the conjecture that the near-UV emission of the dual fluorescence originates from the ketoA rotamer. New experimental results for pure MS in the liquid state are reported and theoretical results compared to them. PMID- 22047239 TI - Interpretation of the photoelectron spectra of superalkali species: Li3O and Li3O . AB - The present paper deals with the interpretation of the photoelectron spectrum of the Li(3)O(-). After several failed attempts to attribute all of the observed peaks in the experimental spectrum to anionic species, neutral species were considered assuming a sequential two-photon absorption mechanism. We find that only two of the six observed peaks can be attributed to photodetachments and that all other observed features can be assigned to ionizations from the ground and excited states of the neutral. Nuclear distributions other than three lithium atoms surrounding the oxygen are not likely to be stable. The interpretation of the experimental peak located at about 1.2 eV remains challenging. It can either be attributed to the second electron detachment (involving the HOMO -1 orbital) energy from the anion's triplet C(2v) state or to higher excited states (involving HOMO +10, 11, 12... orbitals) of the neutral species. Furthermore, we have examined the influence of vibrational displacements on the location of the observed peaks. We find that this effect is smaller than 0.05 eV and, therefore, must be considered as negligible. PMID- 22047240 TI - Photoelectron spectroscopy of the molecular anions, Li3O- and Na3O-. AB - The molecular anions, Li(3)O(-) and Na(3)O(-) were produced by laser vaporization and studied via anion photoelectron spectroscopy. Li(3)O(-) and Na(3)O(-) are the negative ions of the super-alkali neutral molecules, Li(3)O and Na(3)O. A two photon process involving the photodetachment of electrons from the Li(3)O(-) and Na(3)O(-) anions and the photoionization of electrons from the resulting Li(3)O and Na(3)O neutral states was observed. The assignment of the Li(3)O(-) photoelectron spectrum was based on computational results provided by Zein and Ortiz [J. Chem. Phys. 135, 164307 (2011)]. PMID- 22047241 TI - Ultrafast non-adiabatic dynamics of methyl substituted ethylenes: the pi3s Rydberg state. AB - Excited state unimolecular reactions of some polyenes exhibit localization of their dynamics at a single ethylenic double bond. Here we present studies of the fundamental photophysical processes in the ethylene unit itself. Combined femtosecond time-resolved photoelectron spectroscopy (TRPES) and ab initio quantum chemical calculations was applied to the study of excited state dynamics in cis-butene, trans-butene, trimethylethylene, and tetramethylethylene, following initial excitation to their respective pi3s Rydberg states. The wavelength dependence of the pi3s Rydberg state dynamics of tetramethylethylene was investigated in more detail. The pi3s Rydberg to pipi(*) valence state decay rate varies greatly with substituent: the 1,2-di- and tri-methyl substituted ethylenes (cis-butene, trans-butene, and trimethylethylene) show an ultrafast decay (~20 fs), whereas the fully methylated tetramethylethylene shows a decay rate of 2 to 4 orders of magnitude slower. These observations are rationalized in terms of topographical trends in the relevant potential energy surfaces, as found from ab initio calculations: (1) the barrier between the pi3s state and the pipi* state increases with increasing methylation, and (2) the pi3s/pipi* minimum energy conical intersection displaces monotonically away from the pi3s Franck Condon region with increasing methylation. The use of systematic methylation in combination with TRPES and ab initio computation is emerging as an important tool in discerning the excited state dynamics of unsaturated hydrocarbons. PMID- 22047242 TI - Vibronic coupling in the A2Pi and B2Sigma+ electronic states of the NCS radical. AB - The spin-rovibronic energy levels of the A(2)Pi and B(2)Sigma(+) electronic states of thiocyanate radical have been calculated variationally, using high level ab initio coupled diabatic potential energy surfaces. Computations up to J = 7/2 have been performed, obtaining all levels with K <= 3 (Sigma(1/2),Pi(1/2,3/2),Delta(3/2,5/2),Phi(5/2,7/2)), for energies up to 2000 cm( 1) above the A(000)(2)Pi(3/2) level. The available experimental data have been critically reviewed in the light of the theoretical findings. PMID- 22047243 TI - New ab initio coupled potential energy surfaces for the Br(2P(3/2), 2P(1/2)) + H2 reaction. AB - The three lowest (1A('), 2A('), and 1A('')) adiabatic potential energy surfaces (PESs) for the Br((2)P) + H(2) reactive system have been computed based on the multi-reference configuration interaction (MRCI) method including the Davidson's correction with a large basis set. These three adiabatic PESs have been transformed to a diabatic representation, leading to four coupling potentials. In addition, the spin-orbit matrix elements were also obtained using the Breit-Pauli Hamiltonian and the unperturbed MRCI wavefunctions in the Br + H(2) channel and the transition state region. Consequently, six coupling potentials were obtained and their characteristics were extensively discussed. Nonadiabatic quantum dynamics calculations for this system have been realized with these realistic diabatic potentials instead of previous semi-empirical diabatic potentials. Based on two-state model nonadiabatic calculations for the Br((2)P(3/2), (2)P(1/2)) + H(2) reaction, the Br((2)P(1/2)) + H(2) reaction was found to show less reactivity than the Br((2)P(3/2)) + H(2) reaction at collision energies beyond the threshold of the Br((2)P(3/2)) + H(2) reaction. Our results are consistent with the previous studies on the XH(2) (X = F, Cl) system, which indicate that the adiabatically forbidden channel is dominant at low energies in the open-shell halogen atom plus H(2) reactions. PMID- 22047244 TI - State-to-state quantum dynamics of the N(4S) + OH(X2Pi) -> H(2S) + NO(X 2Pi) reaction. AB - Quantum state-to-state dynamics for the N((4)S) + OH(X( 2)Pi) -> H((2)S) + NO(X( 2)Pi) reaction is reported on an accurate ab initio potential energy surface of the lowest triplet electronic state (a(3)A(")) of HNO/HON. It was found that the reaction is dominated by long-lived resonances supported by the HNO and HON wells. Significant non-reactive scattering was observed, indicating substantial deviations from the statistical limit. Due to the large exothermicity of the reaction, the NO product has hot internal state distributions: its rotational state distribution is inverted and peaks near the highest accessible rotational level; and its vibrational state distribution extends to upsilon = 10 and decays monotonically with the vibrational quantum number. In particular, the predicted product vibrational distribution is in reasonably good agreement with experiment. The calculated differential cross section is dominated by scattering in both the forward and backward directions, consistent with the formation of reaction intermediates. PMID- 22047246 TI - Structure and dynamics of 1,2-dimethoxyethane and 1,2-dimethoxypropane in aqueous and non-aqueous solutions: a molecular dynamics study. AB - Herein, we report a comparative modelling study of 1,2-dimethoxyethane (DME) and 1,2-dimethoxypropane (DMP) at 298 K and 318 K in the liquid state, water mixtures, and at infinite dilution condition in water, methanol, carbon tetrachloride, and n-heptane. Both DME and DMP are united-atom models compatible with GROMOS/OPLS force fields. Calculated thermodynamic and structural properties of the pure DME and DMP liquids resulted in excellent agreement with the experimental data. In aqueous solutions, densities, diffusion coefficients, and concentration dependent conformers of DME, were in agreement with experimental data. The calculated free energy of solvation (DeltaG(hyd)) at 298 K is equal to 22.1 +/- 0.8 kJ mol(-1) in good agreement with the experimental value of 20.2 kJ mol(-1). In addition, the free energy of solvation of DME in non-aqueous solvents follows the trend methanol ~ water < carbon tetrachloride < n-heptane, consistently with the dielectric constant of the solvents. On contrary, the presence of an extra methyl group on chiral carbon makes DMP less soluble than DME in water (DeltaG(hyd) = -16.0 +/- 1.1 kJ mol(-1)) but more soluble in non polar solvents as n-heptane. Finally, for the DMP the chiral discrimination of the two enantiomers was calculated as solvation free energy difference of one DMP isomer in the solution of the other. The obtained value of DeltaDeltaG(RS) = -3.7 +/- 1.4 kJ mol(-1) indicates a net chiral discrimination of the two enantiomers. PMID- 22047247 TI - Inverse Raman bands in ultrafast Raman loss spectroscopy. AB - Ultrafast Raman loss spectroscopy (URLS) is equivalent to anti-Stokes femtosecond stimulated Raman spectroscopy (FSRS), using a broadband probe pulse that extends to the blue of the narrow bandwidth Raman pump, and can be described as inverse Raman scattering (IRS). Using the Feynman dual time-line diagram, the third-order polarization for IRS with finite pulses can be written down in terms of a four time correlation function. An analytic expression is obtained for the latter in the harmonic approximation which facilitates computation. We simulated the URLS of crystal violet (CV) for various resonance Raman pump excitation wavelengths using the IRS polarization expression with finite pulses. The calculated results agreed well with the experimental results of S. Umapathy et al., J. Chem. Phys. 133, 024505 (2010). In the limit of monochromatic Raman pump and probe pulses, we obtain the third-order susceptibility for multi-modes, and for a single mode we recover the well-known expression for the third-order susceptibility, chi(IRS) ((3)), for IRS. The latter is used to understand the mode dependent phase changes as a function of Raman pump excitation in the URLS of CV. PMID- 22047248 TI - Static and pulsed field gradient nuclear magnetic resonance studies of water diffusion in protein matrices. AB - Static field gradient and pulsed field gradient NMR are used to study the temperature dependence of water diffusion in myoglobin and lysozyme matrices for low hydration levels of about 0.3 g/g. We show that in order to determine reliable self-diffusion coefficients D in a broad temperature range, it is very important to consider an exchange of magnetization between water and protein protons, often denoted as cross relaxation. Specifically, upon cooling, the observed stimulated-echo decays, which reflect water diffusion near ambient temperature, become more and more governed by cross relaxation. We demonstrate that comparison of experimental results for inhomogeneous and homogeneous magnetic fields enables successful separation of diffusion and relaxation contributions to the stimulated-echo decays. Making use of this possibility, we find that in the temperature range 230-300 K, the temperature-dependent diffusivities D exhibit a Vogel-Fulcher-Tammann behavior, where water diffusion in the studied protein matrices is substantially slower than in the bulk. By comparing present and previous data, we discuss relations between translational and rotational motions and between short-range and long-range water dynamics in protein matrices. In addition, we critically examine the significance of results from previous applications of NMR diffusometry to the temperature-dependent water diffusion in protein matrices. PMID- 22047249 TI - Response of solid Ne upon photoexcitation of a NO impurity: a quantum dynamics study. AB - The ultrafast geometrical rearrangement dynamics of NO doped cryogenic Ne matrices after femtosecond laser pulse excitation is studied using a quantum dynamical approach based on a multi-dimensional shell model, with the shell radii being the dynamical variables. The Ne-NO interaction being only weakly anisotropic allows the model to account for the main dynamical features of the rare gas solid. Employing quantum wave packet propagation within the time dependent Hartree approximation, both, the static deformation of the solid due to the impurity and the dynamical response after femtosecond excitation, are analysed. The photoinduced dynamics of the surrounding rare gas atoms is found to be a complex high-dimensional process. The approach allows to consider realistic time-dependent femtosecond pulses and the effect of the pulse duration is clearly shown. Finally, using the pulse parameters of previous experiments, pump-probe signals are calculated and found to be in good agreement with experimental results, allowing for a clear analysis of the ultrafast mechanism of the energy transfer into the solid. PMID- 22047250 TI - Vibrational energy transfer and anisotropy decay in liquid water: is the Forster model valid? AB - Ultrafast pump-probe anisotropy experiments have been performed on liquid H(2)O and D(2)O. In both cases, the anisotropy decay is extremely fast (on the order of 100 or 200 fs) and is presumed due to resonant vibrational energy transfer. The experiments have been interpreted in terms of the Forster theory, wherein the rate constant for intermolecular hopping transport is proportional to the inverse sixth power of the distance between the vibrational chromophores. In particular, the anisotropy decay is assumed to be simply related to the survival probability as calculated with the Forster theory. While the theory fits the data well, and is a reasonable model for these systems, there are several assumptions in the theory that might be suspect for water. Using our mixed quantum/classical model for vibrational spectroscopy and dynamics in liquid water, which agrees well with anisotropy decay experiments on the pure liquids as well as H(2)O/D(2)O mixtures, we critically analyze both the survival probability and anisotropy decay, in order to assess the applicability of the Forster theory. PMID- 22047252 TI - Pair force distributions in simple fluids. AB - Analytic expressions are derived for the frequency distribution, P(f), of pair forces, f, and those of their alpha-Cartesian component, f(alpha), or P(f(alpha)), for some typical model simple fluids, expressed in terms of the radial distribution function and known constants. For strongly repulsive inverse power (IP), exponential and Yukawa purely repulsive potentials, P(f) diverges at the origin approximately as ~f(-1), but with different limiting analytic forms. P(f(alpha)) is also shown to diverge as ~f(-1) as f -> 0 for the IP fluid. For the Lennard-Jones potential fluid, P(f) is finite for all f >= 0 but has two singularities for negative f, corresponding to the zero force limit (i.e., f -> 0(-)) and the point of inflection in the potential. The corresponding component force distribution is singular as f(alpha) -> 0 from both positive and negative force sides. The large force limit of P(f), which originates from the close neighbor interactions, is nearly exponential for the IP and LJ fluids, as is also found for granular materials. A more complete picture of force distributions in off-lattice particulate systems as a function of force law and state point (particularly the extent of "thermalization" of the particles) is provided. PMID- 22047251 TI - Vibrational spectroscopy of water in hydrated lipid multi-bilayers. II. Two dimensional infrared and peak shift observables within different theoretical approximations. AB - In a previous report, we calculated the infrared absorption spectrum and both the isotropic and anisotropic pump-probe signals for the OD stretch of isotopically dilute water in dilauroylphosphatidylcholine (DLPC) multi-bilayers as a function of the lipid hydration level. These results were then compared to recent experimental measurements and are in generally good agreement. In this paper, we will further investigate the structure and dynamics of hydration water using molecular dynamics simulations and calculations of the two-dimensional infrared and vibrational echo peak shift observables for hydration water in DLPC membranes. These observables have not yet been measured experimentally, but future comparisons may provide insight into spectral diffusion processes and hydration water heterogeneity. We find that at low hydration levels the motion of water molecules inside the lipid membrane is significantly arrested, resulting in very slow spectral diffusion. At higher hydration levels, spectral diffusion is more rapid, but still slower than in bulk water. We also investigate the effects of several common approximations on the calculation of spectroscopic observables by computing these observables within multiple levels of theory. The impact of these approximations on the resulting spectra affects our interpretation of these measurements and reveals that, for example, the cumulant approximation, which may be valid for certain systems, is not a good approximation for a highly heterogeneous environment such as hydration water in lipid multi-bilayers. PMID- 22047253 TI - Simulated pressure response of crystalline indole. AB - The isostatic pressure response of crystalline indole up to 25 GPa was investigated through static geometry optimization using Tkatchenko-Scheffler dispersion-corrected density functional theory method. Different symmetries were identified in the structural evolution with increased pressure, but no motif transition was observed, owing to the stability of the herringbone (HB) motif for small polycyclic aromatic hydrocarbons. Hirshfeld surface analysis determined that there was an increase in the fraction of H...pi and pi...pi contacts within the high pressure structures, while the fraction of H...H contacts was lowered via geometric rearrangements. It was found that isostatic pressure alone, up to 25 GPa, was not sufficient to induce a chemical reaction due to the poor pi orbital overlap existing within the HB motif. However, the applied pressure sets the stage for an activated chemical reaction when the molecules approach each other along the long molecular axis, with a reaction energy and reaction barrier of 1.05 eV and 1.80 eV per molecular unit, respectively. PMID- 22047255 TI - Computer simulation study of thermodynamic scaling of dynamics of 2Ca(NO3)2.3KNO3. AB - Molecular dynamics (MD) simulations of the glass-former 2Ca(NO(3))(2.3KNO(3), CKN, were performed as a function of temperature at pressures 0.1 MPa, 0.5 GPa, 1.0 GPa, and 2.0 GPa. Diffusion coefficient, relaxation time of the intermediate scattering function, and anion reorientational time were obtained as a function of temperature and densitiy rho. These dynamical properties of CKN scale as rho(gamma)/T with a common value gamma = 1.8 +/- 0.1. The scaling parameter gamma is consistent with the exponent of the repulsive part of an effective intermolecular potential for the repulsion between the atoms at shortest distance in the equilibrium structure of liquid CKN, Ca(2+), and oxygen atoms of NO(3)(-). Correlation between potential energy and virial is obeyed for the short-range terms of the potential function, but not for the whole potential including coulombic interactions. Decoupling of diffusion coefficient and reorientational relaxation time from relaxation time take place at a given rho(gamma)/T value, i.e., breakdown of Stokes-Einstein and Debye-Stokes-Einstein equations result from combined thermal and volume effects. The MD results agree with correlations proposed between long-time relaxation and short-time dynamics, lntau ? 1/, where the mean square displacement concerns a time window of 10.0 ps. It has been found that scales as rho(gamma)/T above and below the glass transition temperature, so that thermodynamic scaling of liquid dynamics can be thought as a consequence of theories relating short- and long-time dynamics, and the more fundamental scaling concerns short-time dynamical properties. PMID- 22047254 TI - X-ray Raman scattering provides evidence for interfacial acetonitrile-water dipole interactions in aqueous solutions. AB - Aqueous solutions of acetonitrile (MeCN) have been studied with oxygen K-edge x ray Raman scattering (XRS) which is found to be sensitive to the interaction between water and MeCN. The changes in the XRS spectra can be attributed to water directly interacting with MeCN and are reproduced by density functional theory calculations on small clusters of water and MeCN. The dominant structural arrangement features dipole interaction instead of H-bonds between the two species as revealed by the XRS spectra combined with spectrum calculations. Small angle x-ray scattering shows the largest heterogeneity for a MeCN to water ratio of 0.4 in agreement with earlier small-angle neutron scattering data. PMID- 22047256 TI - Dynamic mechanism of equivalent conductivity minimum of electrolyte solution. AB - The theory on electric conductivity of electrolyte solutions we have developed [T. Yamaguchi, T. Matsuoka, and S. Koda, J. Chem. Phys. 127, 064508 (2007)] is applied to a model electrolyte solution that shows a minimum of equivalent conductivity as the function of concentration [T. Yamaguchi, T. Akatsuka, and S. Koda, J. Chem. Phys. 134, 244506 (2011)]. The theory succeeds in reproducing the equivalent conductivity minimum, whereas the mode-coupling theory (MCT) underestimates the conductivity in the low-concentration regime. The theory can also reproduce the decrease in the relaxation time of conductivity with increasing the concentration we have demonstrated with a Brownian dynamics simulation. A detailed analysis shows that the relaxation of the conductivity occurs through two processes. The faster one corresponds to the collision between a cation and an anion, and the slower one does to the polarization of the ionic atmosphere. The increase in the equivalent conductivity with concentration is attributed to the decrease in the effect of the ionic atmosphere, which is in turn explained by the fact that the counter ion cannot penetrate into the repulsive core when the Debye screening length is compatible or smaller than the ionic diameter. The same mechanism is also observed in MCT calculation with static structure factor determined by mean-spherical approximation. PMID- 22047257 TI - A few simple rules governing hydrogenation of graphene dots. AB - We investigated binding of hydrogen atoms to small polycyclic aromatic hydrocarbons (PAHs)--i.e., graphene dots with hydrogen-terminated edges--using density functional theory and correlated wavefunction techniques. We considered a number of PAHs with three to seven hexagonal rings and computed binding energies for most of the symmetry unique sites, along with the minimum energy paths for significant cases. The chosen PAHs are small enough to not present radical character at their edges, yet show a clear preference for adsorption at the edge sites which can be attributed to electronic effects. We show how the results, as obtained at different levels of theory, can be rationalized in detail with the help of a few simple concepts derivable from a tight-binding model of the pi electrons. PMID- 22047258 TI - Charge transfer interactions of a Ru(II) dye complex and related ligand molecules adsorbed on Au(111). AB - The interaction of the dye molecule, N3 (cis-bis(isothiocyanato)bis(2,2(') bipyridyl-4,4(')-dicarboxylato)-ruthenium(II)), and related ligand molecules with a Au(111) surface has been studied using synchrotron radiation-based electron spectroscopy. Resonant photoemission spectroscopy (RPES) and autoionization of the adsorbed molecules have been used to probe the coupling between the molecules and the substrate. Evidence of charge transfer from the states near the Fermi level of the gold substrate into the lowest unoccupied molecular orbital (LUMO) of the molecules is found in the monolayer RPES spectra of both isonicotinic acid and bi-isonicotinic acid (a ligand of N3), but not for the N3 molecule itself. Calibrated x-ray absorption spectroscopy and valence band spectra of the monolayers reveals that the LUMO crosses the Fermi level of the surface in all cases, showing that charge transfer is energetically possible both from and to the molecule. A core-hole clock analysis of the resonant photoemission reveals a charge transfer time of around 4 fs from the LUMO of the N3 dye molecule to the surface. The lack of charge transfer in the opposite direction is understood in terms of the lack of spatial overlap between the pi*-orbitals in the aromatic rings of the bi-isonicotinic acid ligands of N3 and the gold surface. PMID- 22047259 TI - Adsorption, diffusion, dewetting, and entrapment of acetone on Ni(111), surface modified silicon, and amorphous solid water studied by time-of-flight secondary ion mass spectrometry and temperature programmed desorption. AB - Interactions of acetone with the silicon surfaces terminated with hydrogen, hydroxyl, and perfluorocarbon are investigated; results are compared to those on amorphous solid water (ASW) to gain insights into the roles of hydrogen bonds in surface diffusion and hydration of acetone adspecies. The surface mobility of acetone occurs at ~60 K irrespective of the surface functional groups. Cooperative diffusion of adspecies results in a 2D liquid phase on the H- and perfluorocarbon-terminated surfaces, whereas cooperativity tends to be quenched via hydrogen bonding on the OH-terminated surface, thereby forming residues that diffuse slowly on the surface after evaporation of the physisorbed species (i.e., 2D liquid). The interaction of acetone adspecies on the non-porous ASW surface resembles that on the OH-terminated Si surface, but the acetone molecules tend to be hydrated on the porous ASW film, as evidenced by their desorption during the glass-liquid transition and crystallization of water. The roles of micropores in hydration of acetone molecules are discussed from comparison with the results using mesoporous Si substrates. PMID- 22047260 TI - Continuous-time photon-stimulated desorption spectroscopy studies on soft x-ray induced reactions of CF3Br adsorbed on Si(111)-7*7. AB - Continuous-time core-level photon-stimulated desorption (PSD) spectroscopy was used to study the soft x-ray-induced reactions of CF(3)Br molecules adsorbed on Si(111)-7*7 near the Si(2p) edge (98-110 eV). The monochromatic synchrotron radiation was employed as a soft x-ray light source in the photon-induced reactions and also as a probe for investigating the produced fluorination states of the bonding surface Si atom in the positive-ion PSD spectroscopy. Several different surface coverages were investigated. The PSD spectra from the low CF(3)Br-covered surfaces show the production of surface SiF species, while those from the high-CF(3)Br-covered surfaces depict the formation of surface SiF, SiF(2), and SiF(3) species. The photolysis cross section of the submonolayer CF(3)Br-covered surface is determined as ~4.3*10(-18) cm(2). A comparison with the results on CF(3)Cl/Si(111)-7*7 surface is discussed. PMID- 22047261 TI - Potential of mean force between identical charged nanoparticles immersed in a size-asymmetric monovalent electrolyte. AB - In a previous theoretical and simulation study [G. I. Guerrero-Garcia, E. Gonzalez-Tovar, and M. Olvera de la Cruz, Soft Matter 6, 2056 (2010)], it has been shown that an asymmetric charge neutralization and electrostatic screening depending on the charge polarity of a single nanoparticle occurs in the presence of a size-asymmetric monovalent electrolyte. This effect should also impact the effective potential between two macroions suspended in such a solution. Thus, in this work we study the mean force and the potential of mean force between two identical charged nanoparticles immersed in a size-asymmetric monovalent electrolyte, showing that these results go beyond the standard description provided by the well-known Derjaguin-Landau-Verwey-Overbeek theory. To include consistently the ion-size effects, molecular dynamics (MD) simulations and liquid theory calculations are performed at the McMillan-Mayer level of description in which the solvent is taken into account implicitly as a background continuum with the suitable dielectric constant. Long-range electrostatic interactions are handled properly in the simulations via the well established Ewald sums method and the pre-averaged Ewald sums approach, originally proposed for homogeneous ionic fluids. An asymmetric behavior with respect to the colloidal charge polarity is found for the effective interactions between two identical nanoparticles. In particular, short-range attractions are observed between two equally charged nanoparticles, even though our model does not include specific interactions; these attractions are greatly enhanced for anionic nanoparticles immersed in standard electrolytes where cations are smaller than anions. Practical implications of some of the presented results are also briefly discussed. A good accord between the standard Ewald method and the pre-averaged Ewald approach is attained, despite the fact that the ionic system studied here is certainly inhomogeneous. In general, good agreement between the liquid theory approach and MD simulations is also found. PMID- 22047262 TI - Electronic level alignment at a metal-molecule interface from a short-range hybrid functional. AB - Hybrid functionals often exhibit a marked improvement over semi-local functionals in the description of the electronic structure of organic materials. Because short-range hybrid functionals, notably the Heyd-Scuseria-Ernzerhof (HSE) functional, can also describe the electronic structure of metals reasonably well, it is interesting to examine to which extent they can correctly describe the electronic structure at metal-organic interfaces. Here, we address this question by comparing HSE calculations with many-body perturbation theory calculations in the GW approximation, or with experimental photoemission data, for two prototypical systems: benzene on graphite and benzene diamine on gold. For both cases, we find that while HSE yields results that are somewhat closer to experiment than those of semi-local functionals, the HSE prediction is still lacking quantitatively by ~1 eV. We show that this quantitative failure arises because HSE does not correctly capture the fundamental gap of the organic or its renormalization by the metal. These discrepancies are traced back to missing long range exchange and correlation components, an explanation which applies to any conventional or short-range hybrid functional. PMID- 22047263 TI - Flow-induced control of chemical turbulence. AB - We report spatiotemporal chaos in the Oregonator model of the Belousov Zhabotinsky reaction. Spatiotemporal chaos spontaneously develops in a regime, where the underlying local dynamics show stable limit cycle oscillations (diffusion-induced turbulence). We show that spatiotemporal chaos can be suppressed by a unidirectional flow in the system. With increasing flow velocity, we observe a transition scenario from spatiotemporal chaos via a regime of travelling waves to a stationary steady state. At large flow velocities, we recover the known regime of flow distributed oscillations. PMID- 22047264 TI - Limit of validity of Ostwald's rule of stages in a statistical mechanical model of crystallization. AB - We have only rules of thumb with which to predict how a material will crystallize, chief among which is Ostwald's rule of stages. It states that the first phase to appear upon transformation of a parent phase is the one closest to it in free energy. Although sometimes upheld, the rule is without theoretical foundation and is not universally obeyed, highlighting the need for microscopic understanding of crystallization controls. Here we study in detail the crystallization pathways of a prototypical model of patchy particles. The range of crystallization pathways it exhibits is richer than can be predicted by Ostwald's rule, but a combination of simulation and analytic theory reveals clearly how these pathways are selected by microscopic parameters. Our results suggest strategies for controlling self-assembly pathways in simulation and experiment. PMID- 22047265 TI - Computer simulation of bottle-brush polymers with flexible backbone: good solvent versus theta solvent conditions. AB - By molecular dynamics simulation of a coarse-grained bead-spring-type model for a cylindrical molecular brush with a backbone chain of N(b) effective monomers to which with grafting density sigma side chains with N effective monomers are tethered, several characteristic length scales are studied for variable solvent quality. Side chain lengths are in the range 5 <= N <= 40, backbone chain lengths are in the range 50 <= N(b) <= 200, and we perform a comparison to results for the bond fluctuation model on the simple cubic lattice (for which much longer chains are accessible, N(b) <= 1027, and which corresponds to an athermal, very good, solvent). We obtain linear dimensions of the side chains and the backbone chain and discuss their N-dependence in terms of power laws and the associated effective exponents. We show that even at the theta point the side chains are considerably stretched, their linear dimension depending on the solvent quality only weakly. Effective persistence lengths are extracted both from the orientational correlations and from the backbone end-to-end distance; it is shown that different measures of the persistence length (which would all agree for Gaussian chains) are not mutually consistent with each other and depend distinctly both on N(b) and the solvent quality. A brief discussion of pertinent experiments is given. PMID- 22047266 TI - Cross-streamline migration of a semiflexible polymer in a pressure driven flow. AB - Experiments and simulations on single alpha-actin filaments in the Poiseuille flow through a microchannel show that the center-of-mass probability density across the channel assumes a bimodal shape as a result of pronounced cross streamline migration. We reexamine the problem and perform Brownian dynamics simulations for a bead-spring chain with bending elasticity. Hydrodynamic interactions between the pointlike beads are taken into account by the two-wall Green tensor of the Stokes equations. Our simulations reproduce the bimodal distribution only when hydrodynamic interactions are taken into account. Numerical results on the orientational order of the end-to-end vector of the model polymer are also presented together with analytical hard-needle expressions at zero flow velocity. We derive a Smoluchowski equation for the center-of-mass distribution and carefully analyze the different contributions to the probability current that causes the bimodal distribution. As for flexible polymers, hydrodynamic repulsion explains the depletion at the wall. However, in contrast to flexible polymers, the deterministic drift current mainly determines migration away from the centerline and thereby depletion at the center. Diffusional currents due to a position-dependent diffusivity become less important with increasing polymer stiffness. PMID- 22047267 TI - Moment estimation for chemically reacting systems by extended Kalman filtering. AB - In stochastic models of chemically reacting systems that contain bimolecular reactions, the dynamics of the moments of order up to n of the species populations do not form a closed system, in the sense that their time-derivatives depend on moments of order n + 1. To close the dynamics, the moments of order n + 1 are generally approximated by nonlinear functions of the lower order moments. If the molecule counts of some of the species have a high probability of becoming zero, such approximations may lead to imprecise results and stochastic simulation is the only viable alternative for system analysis. Stochastic simulation can produce exact realizations of chemically reacting systems, but tends to become computationally expensive, especially for stiff systems that involve reactions at different time scales. Further, in some systems, important stochastic events can be very rare and many simulations are necessary to obtain accurate estimates. The computational cost of stochastic simulation can then be prohibitively large. In this paper, we propose a novel method for estimating the moments of chemically reacting systems. The method is based on closing the moment dynamics by replacing the moments of order n + 1 by estimates calculated from a small number of stochastic simulation runs. The resulting stochastic system is then used in an extended Kalman filter, where estimates of the moments of order up to n, obtained from the same simulation, serve as outputs of the system. While the initial motivation for the method was improving over the performance of stochastic simulation and moment closure methods, we also demonstrate that it can be used in an experimental setting to estimate moments of species that cannot be measured directly from time course measurements of the moments of other species. PMID- 22047268 TI - Determining the DNA stability parameters for the breathing dynamics of heterogeneous DNA by stochastic optimization. AB - We suggest that the thermodynamic stability parameters (nearest neighbor stacking and hydrogen bonding free energies) of double-stranded DNA molecules can be inferred reliably from time series of the size fluctuations (breathing) of local denaturation zones (bubbles). On the basis of the reconstructed bubble size distribution, this is achieved through stochastic optimization of the free energies in terms of simulated annealing. In particular, it is shown that even noisy time series allow the identification of the stability parameters at remarkable accuracy. This method will be useful to obtain the DNA stacking and hydrogen bonding free energies from single bubble breathing assays rather than equilibrium data. PMID- 22047269 TI - A coarse-grain three-site-per-nucleotide model for DNA with explicit ions. AB - The "three sites per nucleotide" (3SPN) model provides a coarse-grained representation of nucleic acids for simulation of molecular processes. Previously, this model has relied on an implicit representation of the surrounding ionic environment at the level of Debye-Huckel theory. In this work, we eliminate this limitation and present an explicit representation of ions, both monovalent and divalent. The coarse-grain ion-ion and ion-phosphate potential energy functions are inferred from all-atom simulations and parameterized to reproduce key features of the local structure and organization of ions in bulk water and in the presence of DNA. The resulting model, 3SPN.1-I, is capable of reproducing the local structure observed in detailed atomistic simulations, as well as the experimental melting temperature of DNA for a range of DNA oligonucleotide lengths, CG-content, Na(+) concentration, and Mg(2+) concentration. PMID- 22047270 TI - Comment on "Reactive force fields for surface chemical reactions: a case study with hydrogen dissociation on Pd surfaces" [J. Chem. Phys. 132, 014704 (2010)]. AB - In a recent paper [Y. Xiao, W. Dong, and H. F. Busnengo, J. Chem. Phys. 132, 014704 (2010)], two of us (Y.X. and W.D.) and H. F. Busnengo reported the parameterization of some reactive force fields (RFF) for describing the dissociative adsorption of H2 on Pd surfaces. They obtained a sufficiently accurate RFF by using the reactive bond order (REBO) formalism of Brenner and showed that the simpler RFF based on the second moment approximation (SMA) failed in giving reliable results. It was concluded that the failure is due to the oversimplified expressions of RFF based on SMA and hence the lack of necessary flexibility. The results of our more recent investigation show that this conclusion needs to be corrected. A more suitable choice of the parameterization conditions allows, in fact, for obtaining a reliable RFF from SMA also. PMID- 22047271 TI - Comment on "Study of dielectric relaxations of anhydrous trehalose and maltose glasses" [J. Chem. Phys. 134, 014508 (2011)]. AB - Very recently Kwon et al. [H.-J. Kwon, J.-A. Seo, H. K. Kim, and Y. H. Hwang, J. Chem. Phys. 134, 014508 (2011)] published an article on the study of dielectric relaxation in trehalose and maltose glasses. They carried out broadband dielectric measurements at very wide range of temperatures covering supercooled liquid as well as glassy state of both saccharides. It is worth to mention that authors have also applied a new method for obtaining anhydrous glasses of trehalose and maltose that enables avoiding their caramelization. Four relaxation processes were identified in dielectric spectra of both saccharides. The slower one was identified as structural relaxation process the next one, not observed by the others, was assigned as Johari-Goldstein (JG) beta-relaxation, while the last two secondary modes were of the same nature as found by Kaminski et al. [K. Kaminski, E. Kaminska, P. Wlodarczyk, S. Pawlus, D. Kimla, A. Kasprzycka, M. Paluch, J. Ziolo, W. Szeja, and K. L. Ngai, J. Phys. Chem. B 112, 12816 (2008)]. In this comment we show that the authors mistakenly assigned the slowest relaxation process as structural mode of disaccharides. We have proven that this relaxation process is an effect of formation of thin layer of air or water between plate of capacitor and sample. The same effect can be observed if plates of capacitor are oxidized. Thus, we concluded that their slowest mode is connected to the dc conduction process while their beta JG process is primary relaxation of trehalose and maltose. PMID- 22047273 TI - Invited review article: Interferometric gravity wave detectors. AB - A direct detection of gravitational waves is still lacking today. A network of several earthbound interferometric detectors is currently operating with a continuously improving sensitivity. The window of interest for observation has a lower cut off in the frequency domain below some tens of hertz, determined by the effect of seismic motion. For larger frequencies, the sensitivity is limited by thermal effects below few hundreds of hertz and by the quantum nature of light above that value. Each of these sources of noise pose a big technological challenge to experimentalists, and there are big expectations for the next generation of detectors. A reduction of thermal effects by at least one order of magnitude will be obtained with new and carefully designed materials. At that point the quantum nature of light will become an issue, and the use of quantum non-demolition techniques will become mandatory. In this review, we discuss interferometric detection of gravitational waves from an instrumental point of view. We try to address conceptually important issues with an audience of non experts in mind. A particular emphasis is given to the description of the current limitations and to the perspectives of beating them. PMID- 22047274 TI - A sample holder for soft x-ray absorption spectroscopy of liquids in transmission mode. AB - A novel sample holder for soft x-ray absorption spectroscopy of liquids in transmission mode based on sample cells with x-ray transparent silicon nitride membranes is introduced. The sample holder allows for a reliable preparation of ultrathin liquid films with an adjustable thickness in the nm-MUm range. This enables measurements of high quality x-ray absorption spectra of liquids in transmission mode, as will be shown for the example of liquid H(2)O, aqueous solutions of 3d-transition metal ions and alcohol-water mixtures. The fine structure of the x-ray absorption spectra is not affected by the sample thickness. No effects of the silicon nitride membranes were observed in the spectra. It is shown how an inhomogeneous thickness of the sample affects the spectra and how this can be avoided. PMID- 22047275 TI - A portable fluorescence detector for fast ultra trace detection of explosive vapors. AB - This paper developed a portable detector based on a specific material-based fluorescent sensing film for an ultra trace detection of explosives, such as 2,4,6-trinitrotoluene (TNT) or its derivate 2,4-dinitrotoluene (DNT), in ambient air or on objects tainted by explosives. The fluorescent sensing films are based on single-layer chemistry and the signal amplification effect of conjugated polymers, which exhibited higher sensitivity and shorter response time to TNT or DNT at their vapor pressures. Due to application of the light emitting diode and the solid state photomultiplier and the cross-correlation-based circuit design technology, the device has the advantages of low-power, low-cost, small size, and an improved signal to noise ratio. The results of the experiments showed that the detector can real-time detect and identify of explosive vapors at extremely low levels; it is suitable for the identification of suspect luggage, forensic analyses, or battlefields clearing. PMID- 22047276 TI - Field-programmable gate array based locking circuit for external cavity diode laser frequency stabilization. AB - We present a locking circuit for external cavity diode lasers implemented on a field-programmable gate array (FPGA). The main advantages over traditional non FPGA-based locking circuits are rapid reconfigurability without any soldering and a friendly user interface. We characterize the lock quality by measuring the linewidth of a locked laser using electromagnetically induced transparency in a Rb vapor cell. PMID- 22047277 TI - Fully automated spatially resolved reflectance spectrometer for the determination of the absorption and scattering in turbid media. AB - We describe a fully automated setup which is based on measurements of the spatially resolved reflectance for the determination of the reduced scattering and absorption coefficients in semi-infinite turbid media. The sample is illuminated with a xenon light source in combination with a monochromator enabling the scan of the wavelength from 450 nm to 950 nm. Reflected light from the sample is detected with a CCD camera providing a high spatial resolution. The essential steps for signal processing including, e.g., the consideration of the optical transfer function and the correct treatment of the background subtraction, are presented. The solutions of the diffusion theory and of the radiative transfer theory are investigated regarding the exact detection and illumination geometry. Systematic errors caused by using the different theories for fitting the optical parameters are characterized. The system was validated using liquid phantoms which contain Intralipid 20% and ink, and the measurement range of the system is specified. Further, we carefully characterized the optical properties of Intralipid 20% in the wavelength range between 450 nm and 950 nm. PMID- 22047278 TI - A magnetic-bottle multi-electron-ion coincidence spectrometer. AB - A novel multi-electron-ion coincidence spectrometer developed on the basis of a 1.5 m-long magnetic-bottle electron spectrometer is presented. Electrons are guided by an inhomogeneous magnetic field to a detector at the end of the flight tube, while a set of optics is used to extract counterpart ions to the same detector, by a pulsed inhomogeneous electric field. This setup allows ion detection with high mass resolution, without impairing the high collection efficiency for electrons. The performance of the coincidence spectrometer was tested with double ionization of carbon disulfide, CS(2) -> CS(2)(2+) + e(-) + e( ), in ultrashort intense laser fields (2.8 * 10(13) W/cm(2), 280 fs, 1030 nm) to clarify the electron correlation below the rescattering threshold. PMID- 22047279 TI - Characterization of near-terahertz complementary metal-oxide semiconductor circuits using a Fourier-transform interferometer. AB - Optical methods for measuring of the emission spectra of oscillator circuits operating in the 400-600 GHz range are described. The emitted power from patch antennas included in the circuits is measured by placing the circuit in the source chamber of a Fourier-transform interferometric spectrometer. The results show that this optical technique is useful for measuring circuits pushing the frontier in operating frequency. The technique also allows the characterization of the circuit by measuring the power radiated in the fundamental and in the harmonics. This capability is useful for oscillator architectures designed to cancel the fundamental and use higher harmonics. The radiated power was measured using two techniques: direct measurement of the power by placing the device in front of a bolometer of known responsivity, and by comparison to the estimated power from blackbody sources. The latter technique showed that these circuits have higher emission than blackbody sources at the operating frequencies, and, therefore, offer potential spectroscopy applications. PMID- 22047280 TI - Simultaneous time and wavelength resolved spectroscopy under two-colour near infrared and terahertz excitation. AB - Time and wavelength resolved spectroscopy requires optical sources emitting very short pulses and a fast detection mechanism capable of measuring the evolution of the output spectrum as a function of time. We use table-top Ti:sapphire lasers and a free-electron laser (FEL) emitting ps pulses as excitation sources and a streak camera coupled to a spectrometer for detection. One of the major aspects of this setup is the synchronization of pulses from the two lasers which we describe in detail. Optical properties of the FEL pulses are studied by autocorrelation and electro-optic sampling measurements. We discuss the advantages of using this setup to perform photoluminescence quenching in semiconductor quantum wells and quantum dots. Carrier redistribution due to pulsed excitation in these heterostructures can be investigated directly. Sideband generation in quantum wells is also studied where the intense FEL pulses facilitate the detection of the otherwise weak nonlinear effect. PMID- 22047281 TI - A line-imaging velocity interferometer technique for shock diagnostics without x ray preheat limitation. AB - A study was conducted with a line-imaging velocity interferometer on sandwich targets at the Shen Guang-III prototype laser facility in China, with the goal of eliminating the preheat effect. A sandwich target structure was used to reduce the x-ray preheat limitation (radiation temperature ~170 eV) in a radiative drive shock experiment. With a thick ablator, the preheat effect appeared before the shock arrived at the window. After adding a shield layer of high-Z material on the ablator, x-rays which penetrated the ablator were so weak that the blank-out effect could not be measured. This experiment indicates that the sandwich target may provide a valuable technique in experiments such as equation of state and shock timing for inertial confinement fusion studies. PMID- 22047282 TI - Research on the fiber Bragg grating sensor for the shock stress measurement. AB - A fiber Bragg grating (FBG) sensor with an unbalanced Mach-Zehnder fiber interferometer for the shock stress measurement is proposed and demonstrated. An analysis relationship between the shock stress and the central reflection wavelength shift of the FBG is firstly derived. In this sensor, the optical path difference of the unbalanced Mach-Zehnder fiber interferometer is ~3.1 mm and the length of the FBG is 2 mm. An arctangent function reduction method, which can avoid sine function's insensitive zone where the shock stress measurement has a reduced accuracy, is presented. A shock stress measurement of water driven by one stage gun (up to 1.4 GPa), with good theoretical accuracy (~10%), is launched. PMID- 22047283 TI - Laser-locked, continuously tunable high resolution cavity ring-down spectrometer. AB - A continuous-wave cavity ring-down spectrometer with sub-MHz precision has been built using the sideband of a frequency stabilized laser as the tunable light source. The sideband is produced by passing the carrier laser beam through an electro-optic modulator (EOM) and then selected by a short etalon on resonance. The carrier laser frequency is locked to a longitude mode of a thermo-stabilized Fabry-Perot interferometer (FPI) with a long-term absolute frequency stability of 0.2 MHz (5 * 10(-10)). Broad and precise spectral scanning is accomplished, respectively, by selecting a different longitudinal mode of the FPI and by tuning the radio-frequency driving the EOM. The air broadened water absorption line at 12,321 cm(-1) was studied to test the performance of the spectrometer. PMID- 22047284 TI - Combined optical and acoustical method for determination of thickness and porosity of transparent organic layers below the ultra-thin film limit. AB - Analysis techniques are needed to determine the quantity and structure of materials composing an organic layer that is below an ultra-thin film limit and in a liquid environment. Neither optical nor acoustical techniques can independently distinguish between thickness and porosity of ultra-thin films due to parameter correlation. A combined optical and acoustical approach yields sufficient information to determine both thickness and porosity. We describe application of the combinatorial approach to measure single or multiple organic layers when the total layer thickness is small compared to the wavelength of the probing light. The instrumental setup allows for simultaneous in situ spectroscopic ellipsometry and quartz crystal microbalance dynamic measurements, and it is combined with a multiple-inlet fluid control system for different liquid solutions to be introduced during experiments. A virtual separation approach is implemented into our analysis scheme, differentiated by whether or not the organic adsorbate and liquid ambient densities are equal. The analysis scheme requires that the film be assumed transparent and rigid (non viscoelastic). We present and discuss applications of our approach to studies of organic surfactant adsorption, self-assembled monolayer chemisorption, and multiple-layer target DNA sensor preparation and performance testing. PMID- 22047285 TI - Detection of atomic and molecular mega-electron-volt projectiles using an x-ray charged coupled device camera. AB - We show that an x-ray charge coupled device (CCD) may be used as a particle detector for atomic and molecular mega-electron-volt (MeV) projectiles of around a few hundred keV per atomic mass unit. For atomic species, spectroscopic properties in kinetic energy measurements (i.e., linearity and energy resolution) are found to be close to those currently obtained with implanted or surface barrier silicon particle detectors. For molecular species, in order to increase the maximum kinetic energy detection limit, we propose to put a thin foil in front of the CCD. This foil breaks up the molecules into atoms and spreads the charges over many CCD pixels and therefore avoiding saturation effects. This opens new perspectives in high velocity molecular dissociation studies with accelerator facilities. PMID- 22047286 TI - Efficient spin resolved spectroscopy observation machine at Hiroshima Synchrotron Radiation Center. AB - Highly efficient spin- and angle-resolved photoelectron spectrometer named ESPRESSO (Efficient SPin REsolved SpectroScopy Observation) machine has been developed at the beamline BL-9B in Hiroshima Synchrotron Radiation Center. Combination of high-resolution hemispherical electron analyzer and the high efficient spin detector based on very low energy electron diffraction by the ferromagnetic target makes the high-energy resolution and angular resolution compatible with spin- and angle-resolved photoemission (SARPES) measurement. 7.5 meV in energy and +/-0.18 degrees in angular resolution have been achieved with spin resolution. The ESPRESSO machine, combination of quick energy-band dispersion measurement and Fermi surface mapping by two-dimensional electron detector for the spin integrated ARPES and the high-efficient spin analysis by the efficient spin detector realizes the comprehensive investigation of spin electronic structure of materials. PMID- 22047287 TI - The response of CR-39 nuclear track detector to 1-9 MeV protons. AB - The response of CR-39 nuclear track detector (TasTrak((r))) to protons in the energy range of 0.92-9.28 MeV has been studied. Previous studies of the CR-39 response to protons have been extended by examining the piece-to-piece variability in addition to the effects of etch time and etchant temperature; it is shown that the shape of the CR-39 response curve to protons can vary from piece-to-piece. Effects due to the age of CR-39 have also been studied using 5.5 MeV alpha particles over a 5-year period. Track diameters were found to degrade with the age of the CR-39 itself rather than the age of the tracks, consistent with previous studies utilizing different CR-39 over shorter time periods. PMID- 22047288 TI - Edge and core Thomson scattering systems and their calibration on the ASDEX Upgrade tokamak. AB - A new 10 channel Thomson scattering (TS) system was installed on the ASDEX Upgrade tokamak to measure radial profiles of electron density and temperature at the plasma edge with high radial resolution. Together with the already existing TS system, which is now used for the core plasma, electron density and temperature profiles extending from the edge to the core are now obtained in a single discharge. The TS systems are relatively calibrated by an optical parametric oscillator. PMID- 22047289 TI - Techniques for the measurement of disruption halo currents in the National Spherical Torus Experiment. AB - This paper describes techniques for measuring halo currents, and their associated toroidal peaking, in the National Spherical Torus Experiments [M. Ono et al., Nucl. Fusion 40, 557 (2000)]. The measurements are based on three techniques: (1) measurement of the toroidal field created by the poloidal halo current, either with segmented Rogowski coils or discrete toroidal field sensors, (2) the direct measurement of halo currents into specially instrument tiles, and (3) small Rogowski coils placed on the mechanical supports of in-vessel components. For the segmented Rogowski coils and discrete toroidal field detectors, it is shown that the toroidal peaking factor inferred from the data is significantly less than the peaking factor of the underlying halo current distribution, and a simple model is developed to relate the two. For the array of discrete toroidal field detectors and small Rogowski sensors, the compensation steps that are used to isolate the halo current signal are described. The electrical and mechanical design of compact under-tile resistive shunts and mini-Rogowski coils is described. Example data from the various systems are shown. PMID- 22047290 TI - Development of a compact permanent magnet helicon plasma source for ion beam bioengineering. AB - A compact helicon plasma source was developed as a millimeter-sized ion source for ion beam bioengineering. By employing a stacked arrangement of annular-shaped permanent magnets, a uniform axial magnetic flux density up to 2.8 kG was obtained. A cost effective 118 MHz RF generator was built for adjusting forward output power from 0 to 40 W. The load impedance and matching network were then analyzed. A single loop antenna and circuit matching elements were placed on a compact printed circuit board for 50 Omega impedance matching. A plasma density up to 1.1 * 10(12) cm(-3) in the 10 mm diameter tube under the magnetic flux density was achieved with 35 W applied RF power. PMID- 22047291 TI - Deconvolution of Stark broadened spectra for multi-point density measurements in a flow Z-pinch. AB - Stark broadened emission spectra, once separated from other broadening effects, provide a convenient non-perturbing means of making plasma density measurements. A deconvolution technique has been developed to measure plasma densities in the ZaP flow Z-pinch experiment. The ZaP experiment uses sheared flow to mitigate MHD instabilities. The pinches exhibit Stark broadened emission spectra, which are captured at 20 locations using a multi-chord spectroscopic system. Spectra that are time- and chord-integrated are well approximated by a Voigt function. The proposed method simultaneously resolves plasma electron density and ion temperature by deconvolving the spectral Voigt profile into constituent functions: a Gaussian function associated with instrument effects and Doppler broadening by temperature; and a Lorentzian function associated with Stark broadening by electron density. The method uses analytic Fourier transforms of the constituent functions to fit the Voigt profile in the Fourier domain. The method is discussed and compared to a basic least-squares fit. The Fourier transform fitting routine requires fewer fitting parameters and shows promise in being less susceptible to instrumental noise and to contamination from neighboring spectral lines. The method is evaluated and tested using simulated lines and is applied to experimental data for the 229.69 nm C III line from multiple chords to determine plasma density and temperature across the diameter of the pinch. These measurements are used to gain a better understanding of Z pinch equilibria. PMID- 22047292 TI - Design and use of an Elsasser probe for analysis of Alfven wave fields according to wave direction. AB - We have designed an electric and magnetic field probe which simultaneously measure both quantities in the directions perpendicular to the background magnetic field for application to Alfven wave experiments in the Large Plasma Device at UCLA. This new probe allows for the projection of measured wave fields onto generalized Elsasser variables. Experiments were conducted in a singly ionized He plasma at 1850 G in which propagation of Alfven waves was observed using this new probe. We demonstrate that a clear separation of transmitted and reflected signals and determination of Poynting flux and Elsasser variables can be achieved. PMID- 22047293 TI - Application of an impedance matching transformer to a plasma focus. AB - A plasma focus was constructed using an impedance matching transformer to improve power transfer between the pulse power and the dynamic plasma load. The system relied on two switches and twelve transformer cores to produce a 100 kA pulse in short circuit on the secondary at 27 kV on the primary with 110 J stored. With the two transformer systems in parallel, the Thevenin equivalent circuit parameters on the secondary side of the driver are: C = 10.9 MUF, V(0) = 4.5 kV, L = 17 nH, and R = 5 mOmega. An equivalent direct drive circuit would require a large number of switches in parallel, to achieve the same Thevenin equivalent. The benefits of this approach are replacement of consumable switches with non consumable transformer cores, reduction of the driver inductance and resistance as viewed by the dynamic load, and reduction of the stored energy to produce a given peak current. The system is designed to operate at 100 Hz, so minimizing the stored energy results in less load on the thermal management system. When operated at 1 Hz, the neutron yield from the transformer matched plasma focus was similar to the neutron yield from a conventional (directly driven) plasma focus at the same peak current. PMID- 22047294 TI - Detection efficiency vs. cathode and anode separation in cylindrical vacuum photodiodes used for measuring x-rays from plasma focus device. AB - A qualitative study on the performance of cylindrical vacuum photodiodes (VPDs) for x-ray detection in plasma focus device has been carried out. Various parameters of VPD such as electrode's diameter, electrode's separation, and its sensitivity are experimentally tested in plasma focus environment. For the first time it is found experimentally that the electrode-separation in the lateral direction of the two coaxial electrodes of cylindrical VPD also plays an important role to increase the efficiency of the detector. The efficiency is found to be highest for the detector with smaller cathode-anode lateral gap (1.5 mm) with smaller photo cathode diameter (10 mm). A comparison between our VPD with PIN (BPX-65) diode as an x-ray detector has also been made. PMID- 22047295 TI - Time-frequency analysis for microwave reflectometry data processing in the HL-2A tokamak. AB - The Choi-Williams distribution (CWD) technique is introduced as a time-frequency tool for processing data measured from the new developed homodyne and the fixed frequency reflectometry in the HL-2A tokamak. The comparison between spectrogram and CWD for the simulated signal is presented. It indicates that the CWD can greatly improve the representation of the time-frequency content of the multi components signal. Its effectiveness is demonstrated through two applications in HL-2A, which are the extraction of beat frequencies from the frequency modulated continuous wave reflectometry (FM-CW) and the characterizing of the fluctuations. The density profile inversed from the group delay of the FM-CW and the density fluctuations deduced from the fixed-frequency reflectometry would be more reliable and accurate by using the CWD technique. PMID- 22047296 TI - Properties of a capillary discharge-produced argon plasma waveguide for shorter wavelength source application. AB - We report the operation of a discharge-produced argon (Ar) plasma waveguide in an alumina (Al(2)O(3)) capillary to guide a 10(16)-W/cm(2) ultrashort laser pulse for shorter wavelength light sources at high repetition rate operation. The electron density in the plasma channel was measured to be 1 * 10(18) cm(-3). Modeling with a one-dimensional magnetrohydrodynamic code was used to evaluate the degree of ionization of Ar in the preformed plasma channel. The observed spectrum of the laser pulse after propagation in the argon plasma waveguide was not modified and was well reproduced by a particle in cell simulation. PMID- 22047297 TI - Field programmable gate array based reconfigurable scanning probe/optical microscope. AB - The increasing popularity of nanometrology and nanospectroscopy has pushed researchers to develop complex new analytical systems. This paper describes the development of a platform on which to build a microscopy tool that will allow for flexibility of customization to suit research needs. The novelty of the described system lies in its versatility of capabilities. So far, one version of this microscope has allowed for successful near-field and far-field fluorescence imaging with single molecule detection sensitivity. This system is easily adapted for reflection, polarization (Kerr magneto-optical (MO)), Raman, super-resolution techniques, and other novel scanning probe imaging and spectroscopic designs. While collecting a variety of forms of optical images, the system can simultaneously monitor topographic information of a sample with an integrated tuning fork based shear force system. The instrument has the ability to image at room temperature and atmospheric pressure or under liquid. The core of the design is a field programmable gate array (FPGA) data acquisition card and a single, low cost computer to control the microscope with analog control circuitry using off the-shelf available components. A detailed description of electronics, mechanical requirements, and software algorithms as well as examples of some different forms of the microscope developed so far are discussed. PMID- 22047298 TI - A compact sub-Kelvin ultrahigh vacuum scanning tunneling microscope with high energy resolution and high stability. AB - We designed a scanning tunneling microscope working at sub-Kelvin temperatures in ultrahigh vacuum (UHV) in order to study the magnetic properties on the nanoscale. An entirely homebuilt three-stage cryostat is used to cool down the microscope head. The first stage is cooled with liquid nitrogen, the second stage with liquid (4)He. The third stage uses a closed-cycle Joule-Thomson refrigerator of a cooling power of 1 mW. A base temperature of 930 mK at the microscope head was achieved using expansion of (4)He, which can be reduced to ~400 mK when using (3)He. The cryostat has a low liquid helium consumption of only 38 ml/h and standing times of up to 280 h. The fast cooling down of the samples (3 h) guarantees high sample throughput. Test experiments with a superconducting tip show a high energy resolution of 0.3 meV when performing scanning tunneling spectroscopy. The vertical stability of the tunnel junction is well below 1 pm (peak to peak) and the electric noise floor of tunneling current is about 6fA/?Hz. Atomic resolution with a tunneling current of 1 pA and 1 mV was achieved on Au(111). The lateral drift of the microscope at stable temperature is below 20 pm/h. A superconducting spilt-coil magnet allows to apply an out-of-plane magnetic field of up to 3 T at the sample surface. The flux vortices of a Nb(110) sample were clearly resolved in a map of differential conductance at 1.1 K and a magnetic field of 0.21 T. The setup is designed for in situ preparation of tip and samples under UHV condition. PMID- 22047299 TI - Vector potential photoelectron microscopy. AB - A new class of electron microscope has been developed for the chemical microanalysis of a wide range of real world samples using photoelectron spectroscopy. Highly structured, three-dimensional samples, such as fiber mats and fracture surfaces can be imaged, as well as insulators and magnetic materials. The new microscope uses the vector potential field from a solenoid magnet as a spatial reference for imaging. A prototype instrument has demonstrated imaging of uncoated silk, magnetic steel wool, and micron-sized single strand tungsten wires. PMID- 22047300 TI - Measurement sensitivity improvement in tapping-mode atomic force microscopy through bi-harmonic drive signal. AB - This article presents a novel method to improve the measurement sensitivity and reduce impact forces in tapping-mode atomic force microscopy by reshaping the tip trajectory. A tapping drive signal composed of two harmonics is used to generate an oscillating trajectory with a broader valley compared to the typical sinusoidal trajectory. The wide broad valley reduces the velocity of the tip in the vicinity of the sample and allots a greater portion of each period in the vicinity of the sample. Numerical simulations show that this results in decreased impact force and increased sensitivity of the cantilever oscillation to changes in tip-sample offset. Experimental results demonstrate an increase in image sharpness and decrease in tip wear using the bi-harmonic driving signal. PMID- 22047301 TI - A simple approach to neutral atom microscopy. AB - Scanning surfaces using a beam of noncharged atoms or molecules allows for especially nondestructive and low-energy surface imaging, with the potential to obtain new information about surfaces that cannot be easily obtained otherwise. We have developed a new approach, operating with the sample at a close working distance from an aperture, the need for optics to focus the beam is obviated. Compared to more complex approaches, the theoretical performance has no other disadvantage than the short working distance. Resolution of 1.5 MUm has been achieved, and submicron resolution appears to be practical. Construction of the microscope and results are presented, including first images done in reflection mode, theory for optimization of the design and avenues for future improvement. PMID- 22047302 TI - Calibration method of tilt and azimuth angles for alignment of TEM tomographic tilt series. AB - This paper describes the calibration method of the tilt and azimuth angles of specimen using a digital protractor and a laser autocollimator for alignment of electron tomography. It also suggests an easy method to check whether the specimen is tilted by 180.0 degrees , and whether the azimuth angle is 0.0 degrees ; the method involves the use of two images of a rod-shaped specimen collected before and after a 180.0 degrees tilt. The method is based on the assumption that these images are symmetric about the tilt axis when the azimuth angle is 0.0 degrees . In addition, we used an experiment to demonstrate the effect of the incorrect angles on reconstructed images and simulated the image quality against distance away from tilt axis. PMID- 22047303 TI - A method to track rotational motion for use in single-molecule biophysics. AB - The double helical nature of DNA links many cellular processes such as DNA replication, transcription, and repair to rotational motion and the accumulation of torsional strain. Magnetic tweezers (MTs) are a single-molecule technique that enables the application of precisely calibrated stretching forces to nucleic acid tethers and to control their rotational motion. However, conventional magnetic tweezers do not directly monitor rotation or measure torque. Here, we describe a method to directly measure rotational motion of particles in MT. The method relies on attaching small, non-magnetic beads to the magnetic beads to act as fiducial markers for rotational tracking. CCD images of the beads are analyzed with a tracking algorithm specifically designed to minimize crosstalk between translational and rotational motion: first, the in-plane center position of the magnetic bead is determined with a kernel-based tracker, while subsequently the height and rotation angle of the bead are determined via correlation-based algorithms. Evaluation of the tracking algorithm using both simulated images and recorded images of surface-immobilized beads demonstrates a rotational resolution of 0.1 degrees , while maintaining a translational resolution of 1-2 nm. Example traces of the rotational fluctuations exhibited by DNA-tethered beads confined in magnetic potentials of varying stiffness demonstrate the robustness of the method and the potential for simultaneous tracking of multiple beads. Our rotation tracking algorithm enables the extension of MTs to magnetic torque tweezers (MTT) to directly measure the torque in single molecules. In addition, we envision uses of the algorithm in a range of biophysical measurements, including further extensions of MT, tethered particle motion, and optical trapping measurements. PMID- 22047304 TI - Use of scanning probe microscopy to study the evolution of nanometer sized liquid structures. AB - The evolution of the profile of nanometer sized water drops on a mica surface has been studied through hydration scanning probe microscopy. A time range from a few seconds down to a fraction of millisecond after the formation of the drop has been explored. This high time resolution has been obtained by sampling a series of statistically equivalent drops. This approach also avoids any probe interference during the drop evolution process. PMID- 22047305 TI - Magnifying lens for 800 MeV proton radiography. AB - This article describes the design and performance of a magnifying magnetic-lens system designed, built, and commissioned at the Los Alamos National Laboratory (LANL) for 800 MeV flash proton radiography. The technique of flash proton radiography has been developed at LANL to study material properties under dynamic loading conditions through the analysis of time sequences of proton radiographs. The requirements of this growing experimental program have resulted in the need for improvements in spatial radiographic resolution. To meet these needs, a new magnetic lens system, consisting of four permanent magnet quadrupoles, has been developed. This new lens system was designed to reduce the second order chromatic aberrations, the dominant source of image blur in 800 MeV proton radiography, as well as magnifying the image to reduce the blur contribution from the detector and camera systems. The recently commissioned lens system performed as designed, providing nearly a factor of three improvement in radiographic resolution. PMID- 22047306 TI - Magneto-optical Kerr effect susceptometer for the analysis of magnetic domain wall dynamics. AB - Domain wall dynamics in thin magnetic films with perpendicular and in-plane anisotropy is studied using a novel magneto-optical Kerr effect susceptometery method. The method allows for measurements of domain wall motion under ac field excitation and the analysis of dynamic modes as a function of driving frequency and magnetic field amplitude. Domain wall dynamics in the perpendicular anisotropy system, a Co/Pt multilayer, is characterized by thermally activated creep motion. For this dynamic mode, a polydispersivity exponent of beta = 0.50 +/- 0.03 is derived at small excitation energy, which is in excellent agreement with theoretical models. The dynamics of the other system, a Co wire with transverse uniaxial anisotropy, is dominated by viscous slide motion in a regular magnetic stripe pattern. Analytical expressions are derived for this magnetic configuration and by using these expressions, accurate values for the depinning field and the domain wall mobility are extracted from the susceptibility measurements. PMID- 22047307 TI - The extended surface forces apparatus. IV. Precision static pressure control. AB - We report on design and performance of an extended surface forces apparatus (eSFA) built into a pressurized system. The aim of this instrument is to provide control over static pressure and temperature to facilitate direct surface force experiments in equilibrium with fluids at different loci of their phase diagram. We built an autoclave that can bear a miniature eSFA. To avoid mechanical or electrical feedtroughs the miniature apparatus uses an external surface coarse approach stage under ambient conditions. The surface separation is thus pre adjusted to approximately ~3 MUm before sliding the apparatus into the autoclave. Inside the autoclave, the surface separation can be further controlled with a magnetic drive at sub-Angstrom precision over a 14 MUm range. The autoclave pressure can then be set and maintained between 20 mbar and 170 bars with few mbar precision. The autoclave is connected to a specially designed pressurization system to precondition the fluids. The temperature can be controlled between -20 and 60 degrees C with few mK precision. We demonstrate the operation of the instrument in the case of gaseous or liquid carbon dioxide. Thanks to a consequent decoupling of the eSFA mechanical loop from the autoclave structure, the obtained measurement stability and reproducibility, at elevated pressures, is comparable to the one established for the conventional eSFA, operated under ambient conditions. PMID- 22047308 TI - Alternating-current induced thermal fatigue of gold interconnects with nanometer scale thickness and width. AB - With dramatic reduction in sizes of microelectronic devices, the characteristic width and thickness of interconnects in large-scale integrated circuits have reached nanometer scale. Thermal fatigue damage of so small interconnects has attracted more and more attentions. In this work, thermal fatigue of Au interconnects, 35 nm thick and 0.1-5 MUm wide, is investigated by applying various alternating current densities to generate cycling temperature and strain in them. A multi-probe measuring system is installed in a scanning electron microscope and a probe-type temperature sensor is for the first time introduced into the system for real-time measuring the temperatures on the pads of the tested interconnects. A one-dimensional heat conduction equation, which uses measured temperatures on the pads as boundary conditions and includes a term of heat dissipation through the interface between the interconnect and the oxidized silicon substrate, is proposed to calculate the time-resolved temperature distribution along the Au interconnects. The measured fatigue lifetimes are presented versus current density and thermal cyclic strain, and the results show that narrower Au lines are more reliable. The failure mechanism of those Au interconnects differs from what is observed in thick interconnects with relatively larger grain size. Topography change caused by localized plasticity on the less-constrained surfaces of the interconnects have not been observed. Instead, grain growing and reorienting due to local temperature varying appear, and grain boundary migration and mergence take place during high temperature fatigue in such thin and narrow interconnects. These results seem to reflect a strain-induced boundary migration mechanism, and the damage morphology also suggests that fatigue of the interconnects with decreased grain size and film thickness is controlled by diffusive mechanisms and interface properties rather than by dislocation glide. Open circuit eventually took place by melting at a region of severely damage cross-sectional area with the grain growing and reorienting. PMID- 22047309 TI - Quantitative calibration of radiofrequency NMR Stark effects. AB - Nuclear magnetic resonance (NMR) Stark responses can occur in quadrupolar nuclei for an electric field oscillating at twice the usual NMR frequency (2omega(0)). Calibration of responses to an applied E field is needed to establish nuclear spins as probes of native E fields within material and molecular systems. We present an improved approach and apparatus for accurate measurement of quadrupolar Stark effects. Updated values of C(14) (the response parameter in cubic crystals) were obtained for both (69)Ga and (75)As in GaAs. Keys to improvement include a modified implementation of voltage dividers to assess the 2omega(0) amplitude, |E|, and the stabilization of divider response by reduction of stray couplings in 2omega(0) circuitry. Finally, accuracy was enhanced by filtering sets of |E| through a linear response function that we established for the radiofrequency amplifier. Our approach is verified by two types of spectral results. Steady-state 2omega(0) excitation to presaturate NMR spectra yielded C(14) = (2.59 +/- 0.06) * 10(12) m(-1) for (69)Ga at room-temperature and 14.1 T. For (75)As, we obtained (3.1 +/- 0.1) * 10(12) m(-1). Both values reconcile with earlier results from 77 K and below 1 T, whereas current experiments are at room temperature and 14.1 T. Finally, we present results where few-microsecond pulses of the 2omega(0) field induced small (tens of Hz) changes in high-resolution NMR line shapes. There too, spectra collected vs |E| agree with the model for response, further establishing the validity of our protocols to specify |E|. PMID- 22047310 TI - High sensitivity detection of radio-frequency modulated magnetic moment in semiconductors. AB - An experimental setup has been realized to measure weak magnetic moments which can be modulated at radio frequencies (~1-5 MHz). Using an optimized radio frequency (RF) pickup coil and lock-in amplifier, an experimental sensitivity of 10(-15) Am(2) corresponding to 10(-18) emu has been demonstrated with a 1 s time constant. The detection limit at room temperature is 9.3 * 10(-16) Am(2)/?Hz limited by Johnson noise of the coil. The setup has been used to directly measure the magnetic moment due to a small number (~7 * 10(8)) of spin polarized electrons generated by polarization modulated optical radiation in GaAs and Ge. PMID- 22047311 TI - Characteristic impedance and capacitance analysis of Blumlein type pulse forming line of accelerator based on tape helix. AB - In this paper, the electromagnetic dispersion theory and the classic telegraph equations were combined to calculate the important parameters of the helical Blumlein pulse forming line (BPFL) of accelerator based on tape helix. In the work band of the BPFL at several hundred ns range, electromagnetic dispersion characteristics were almost determined by the zeroth harmonic. In order to testify the dispersion theory of BPFL in this paper, filling dielectrics, such as de-ionized water, transformer oil, and air were employed in the helical BPFL, respectively. Parameters such as capacitance, inductance, characteristic impedance, and pulse duration of the BPFL were calculated. Effects of dispersion on these parameters were analyzed. Circuit simulation and electromagnetic simulation were carried out to prove these parameters of BPFL filled with these three kinds of dielectrics, respectively. The accelerator system was set up, and experimental results also corresponded to the theoretical calculations. The average theoretical errors of impedances and pulse durations were 3.5% and 3.4%, respectively, which proved the electromagnetic dispersion analyses in this paper. PMID- 22047312 TI - Megavolt range voltage measurement in vacuum through a short-circuited line. AB - Method of voltage measurement at a vacuum load by means of homogeneous short circuited vacuum-isolated line was considered. Prior to appearance of a measured high-voltage pulse, a magnetic field is formed in the line due to the bias current. Biasing provides fulfillment of magnetic electron isolation conditions and strong pressing of an electron layer down to the cathode already at the voltage wave front. As a result, a weak change of the "hot" line wave impedance is achieved during a pulse. Theoretical consideration and numerical simulation of the measuring line operation in the presence of bias current basing the applicability of the method was carried out. The method was used to determine the plasma-filled diode voltage at a megavolt voltage level. The absence of electron leakages at the voltage wave propagation of the amplitude ~1 MV along the measuring line of the length 2.3 m with the wave impedance of 136 Omega and initial bias current of ~6 kA was realized. PMID- 22047313 TI - Precision waveguide system for measurement of complex permittivity of liquids at frequencies from 60 to 90 GHz. AB - We describe a variable path length waveguide setup developed to accurately measure the complex dielectric permittivity of liquids. This is achieved by measuring the complex scattering parameter of the liquid in a waveguide section with a vector network analyzer in combination with an E-band frequency converter. The automated measurement procedure allows fast acquisition at closely spaced intervals over the entire measurement bandwidth: 60-90 GHz. The presented technique is an absolute method and as such is not prone to calibration errors. The technique is suited to investigate low-loss as well as high-loss liquids in contrast to similar setups described previously. We present measurements for a high-loss liquid (water), an intermediate-loss sample (ethanol), and for nearly loss-less n-octane. Due to the available phase information, the present data have an improved accuracy in comparison with literature data. PMID- 22047314 TI - Slippage toughness measurement of soft interface between stiff thin films and elastomeric substrate. AB - Traditional interfacial toughness measurements for thin films on substrate are not appropriate to the structure composed of stiff films and soft substrate. This paper describes a new bending test system to measure the interfacial toughness for the soft interface between stiff films and elastomeric substrate. The experimental setup including the loading stages is easy to operate and scanning electron microscope is used to in situ monitor the interfacial slippage during loading. The proposed bending test is conducted for silicon film on poly(dimethylsiloxane) substrate. This method demonstrates the promising way to measure the slippage toughness of soft interface involving the flexible electronics and the bio-related fields. PMID- 22047315 TI - Cryogenic ultra-low-noise SiGe transistor amplifier. AB - An ultra-low-noise one-stage SiGe heterojunction bipolar transistor amplifier was designed for cryogenic temperatures and a frequency range of 10 kHz-100 MHz. A noise temperature T(N) ~ 1.4 K was measured at an ambient temperature of 4.2 K at frequencies between 100 kHz and 100 MHz for a source resistance of ~50 Omega. The voltage gain of the amplifier was 25 dB at a power consumption of 720 MUW. The input voltage noise spectral density of the amplifier is about 35 pV/?Hz. The low noise resistance and power consumption makes the amplifier suitable for readout of resistively shunted DC SQUID magnetometers and amplifiers. PMID- 22047316 TI - Pound-locking for characterization of superconducting microresonators. AB - We present a new application and implementation of the Pound-locking technique for the interrogation of superconducting microresonators. We discuss how by comparing against stable frequency sources this technique can be used to characterize properties of resonators that cannot be accessed using traditional methods. Specifically, by analyzing the noise spectra and the Allan deviation, we obtain valuable information about the nature of the noise in superconducting planar resonators. This technique also greatly improves the read-out accuracy and measurement throughput compared to conventional methods. PMID- 22047317 TI - A travelling photothermal technique employing pyroelectric detection to measure thermal diffusivity of films and coatings. AB - A travelling thermal wave technique employing optical excitation and pyroelectric detection of thermal waves propagating along a material film/coating on a substrate is described. The method enables direct measurement of thermal diffusivity. The technique involves measurement of the phase lag undergone by an optically excited thermal wave as it propagates along the coating. The set up has been automated for convenient and fast data acquisition and analysis. The technique has been adapted to measurement of thermal diffusivity of a commercial paint sample coated on glass and copper substrates. It is found that thermal diffusivity of the coating is independent of the thermal conductivity of the substrate. Dependence of thermal diffusivity on coating thickness shows exponential increase, with value reaching a constant at a characteristic high thickness. Measurements have been carried out on a few other samples with wide variations in thermal diffusivity, and the results compared with available reports or results obtained following other techniques. Analyses of the results show that the technique allows measurement of thermal diffusivity of coatings and films with uncertainties better than +/-2.5%. PMID- 22047318 TI - Phase behaviour and phase separation kinetics measurement using acoustic arrays. AB - Speed of sound and acoustic wave attenuation are sensitive to fluid phase composition and to the presence of liquid-liquid interfaces. In this work, the use of an acoustic array comprising 64 elements as a non-intrusive sensor for liquid-liquid interface, phase separation kinetics measurement in bulk fluids, and local composition measurement in porous media is illustrated. Three benchmark examples: the phase behaviour of methanol + mixed hexanes and methanol + heptane mixtures at 25.0 degrees C and 1 bar, and Athabasca bitumen + heptane in a synthetic silica porous medium at 22.5 degrees C and 1 bar, illustrate the accuracy of liquid-liquid interface and potential research and industrial applications of the technique. Liquid-liquid interfaces can be detected independently using both speed of sound and acoustic wave attenuation measurements. The precision of the interface location measurement is 300 MUm. As complete scans can be performed at a rate of 1 Hz, phase separation kinetics and diffusion of liquids within porous media are readily tracked. The technique is expected to find application where the fluids or porous media are opaque to visible light and where other imaging techniques are not readily applied, or are too costly. A current limitation is that the acoustic probes must be cooled to less than 315 K in order for them to operate. PMID- 22047319 TI - High-speed phosphor thermometry. AB - Phosphor thermometry is a semi-invasive surface temperature measurement technique utilising the luminescence properties of doped ceramic materials. Typically, these phosphor materials are coated onto the object of interest and are excited by a short UV laser pulse. Up to now, primarily Q-switched laser systems with repetition rates of 10 Hz were employed for excitation. Accordingly, this diagnostic tool was not applicable to resolve correlated temperature transients at time scales shorter than 100 ms. This contribution reports on the first realisation of a high-speed phosphor thermometry system employing a highly repetitive laser in the kHz regime and a fast decaying phosphor. A suitable material was characterised regarding its temperature lifetime characteristic and its measurement precision. Additionally, the influence of laser power on the phosphor coating was investigated in terms of heating effects. A demonstration of this high-speed technique has been conducted inside the thermally highly transient system of an optically accessible internal combustion engine. Temperatures have been measured with a repetition rate of 6 kHz corresponding to one sample per crank angle degree at 1000 rpm. PMID- 22047320 TI - An accurate new method to measure the dimensionless figure of merit of thermoelectric devices based on the complex impedance porcupine diagram. AB - The heat diffusion related f(-1/2) slow decay in the frequency domain transfer function of thermoelectric devices introduces a bias in figure of merit measurement methods that do not take it into account. The bias can range from less than 1% to more than 20% depending on the device. Harman type methods are not immune. Neither is the simple single measurement procedure proposed here on the basis of a complex thermal impedance analysis of the device, but in this case the supporting theory allows evaluating and correcting for the bias with documented accuracy. To this aim, both a theoretical approach based on a priori knowledge of the device and an experimental one based on theory guided measurements are possible and are described in the paper. Typical residual Type B uncertainties after correction can be below 10% of the bias. PMID- 22047321 TI - Non-equilibrium phonon generation and detection in microstructure devices. AB - We demonstrate a method to excite locally a controllable, non-thermal distribution of acoustic phonon modes ranging from 0 to ~200 GHz in a silicon microstructure, by decay of excited quasiparticle states in an attached superconducting tunnel junction (STJ). The phonons transiting the structure ballistically are detected by a second STJ, allowing comparison of direct with indirect transport pathways. This method may be applied to study how different phonon modes contribute to the thermal conductivity of nanostructures. PMID- 22047322 TI - Versatile computer-controlled system for characterization of gas sensing materials. AB - Design of a system used for characterizing gas sensing materials is described. It is distinctive of being able to measure electrical and optical responses of a sample simultaneously, control a number of measurement parameters, perform fast exchange of gaseous environment, and be fully controlled automatically. These features make the system to be versatile in determining most concerned performance indexes of a gas sensing material (e.g., sensitivity, stability, selectivity, response/recovery times, etc.) as functions of various combinations of measurement conditions (e.g., gas concentrations, temperature, total pressure, content of interferants, photo assist, relative humidity, soaking time in a fixed gas concentration, and number of switching cycles in a dynamic test, etc.). Rationales of the designs associated with general gas sensing mechanics are discussed. PMID- 22047323 TI - Implementation of a portable electronic system for providing pain relief to patellofemoral pain syndrome patients. AB - In this study, a portable electromyogram (EMG) system and a stimulator are developed for patellofemoral pain syndrome patients, with the objective of reducing the pain experienced by these patients; the patellar pain is caused by an imbalance between the vastus medialis obliquus (VMO) and the vastus lateralis (VL). The EMG measurement circuit and the electrical stimulation device proposed in this study are specifically designed for the VMO and the VL; they are capable of real-time waveform recording, possess analyzing functions, and can upload their measurement data to a computer for storage and analysis. The system can calculate and record the time difference between the EMGs of the VMO and the VL, as well as the signal strengths of both the EMGs. As soon as the system detects the generation of the EMG of the VL, it quickly calculates and processes the event and stimulates the VMO as feedback through electrical stimulation units, in order to induce its contraction. The system can adjust the signal strength, time length, and the sequence of the electrical stimulation, both manually and automatically. The output waveform of the electrical stimulation circuit is a dual-phase asymmetrical pulse waveform. The primary function of the electrical simulation circuit is to ensure that the muscles contract effectively. The performance of the device can be seen that the width of each pulse is 20-1000 MUs, the frequency of each pulse is 10-100 Hz, and current strength is 10-60 mA. PMID- 22047324 TI - A dynamic gravimetric standard for trace water. AB - A system for generating traceable reference standards of water vapor at trace levels between 5 and 2000 nmol/mol has been developed. It can provide different amount fractions of trace water vapor by using continuous accurate measurements of mass loss from a permeation device coupled with a dilution system based on an array of critical flow orifices. An estimated relative expanded uncertainty of +/ 2% has been achieved for most amount fractions generated. The system has been used in an international comparison and demonstrates excellent comparability with National Metrology Institutes maintaining standards of water vapor in this range using other methods. PMID- 22047325 TI - Large angle and high linearity two-dimensional laser scanner based on voice coil actuators. AB - A large angle and high linearity two-dimensional laser scanner with an in-house ingenious deflection angle detecting system is developed based on voice coil actuators direct driving mechanism. The specially designed voice coil actuators make the steering mirror moving at a sufficiently large angle. Frequency sweep method based on virtual instruments is employed to achieve the natural frequency of the laser scanner. The response shows that the performance of the laser scanner is limited by the mechanical resonances. The closed-loop controller based on mathematical model is used to reduce the oscillation of the laser scanner at resonance frequency. To design a qualified controller, the model of the laser scanner is set up. The transfer function of the model is identified with MATLAB according to the tested data. After introducing of the controller, the nonlinearity decreases from 13.75% to 2.67% at 50 Hz. The laser scanner also has other advantages such as large deflection mirror, small mechanical structure, and high scanning speed. PMID- 22047326 TI - Dust trajectory sensor: accuracy and data analysis. AB - The Dust Trajectory Sensor (DTS) instrument is developed for the measurement of the velocity vector of cosmic dust particles. The trajectory information is imperative in determining the particles' origin and distinguishing dust particles from different sources. The velocity vector also reveals information on the history of interaction between the charged dust particle and the magnetospheric or interplanetary space environment. The DTS operational principle is based on measuring the induced charge from the dust on an array of wire electrodes. In recent work, the DTS geometry has been optimized [S. Auer, E. Grun, S. Kempf, R. Srama, A. Srowig, Z. Sternovsky, and V Tschernjawski, Rev. Sci. Instrum. 79, 084501 (2008)] and a method of triggering was developed [S. Auer, G. Lawrence, E. Grun, H. Henkel, S. Kempf, R. Srama, and Z. Sternovsky, Nucl. Instrum. Methods Phys. Res. A 622, 74 (2010)]. This article presents the method of analyzing the DTS data and results from a parametric study on the accuracy of the measurements. A laboratory version of the DTS has been constructed and tested with particles in the velocity range of 2-5 km/s using the Heidelberg dust accelerator facility. Both the numerical study and the analyzed experimental data show that the accuracy of the DTS instrument is better than about 1% in velocity and 1 degrees in direction. PMID- 22047327 TI - Photoelectron-photofragment coincidence spectroscopy in a cryogenically cooled linear electrostatic ion beam trap. AB - A cryogenically cooled linear electrostatic ion beam trap for use in photoelectron-photofragment coincidence (PPC) spectroscopy is described. Using this instrument, anions created in cold, low-duty-cycle sources can be stored for many seconds in a ~20 K environment to cool radiatively, removing energetic uncertainties due to vibrationally excited precursor anions. This apparatus maintains a well-collimated beam necessary for high-resolution fragment imaging and the high experimental duty cycle needed for coincidence experiments. Ion oscillation is bunched and phase-locked to a modelocked laser, ensuring temporal overlap between ion bunches and laser pulses and that ions are intersected by the laser only when travelling in one direction. An electron detector is housed in the field-free center of the trap, allowing PPC experiments to be carried out on ions while they are stored and permitting efficient detection of 3-dimensional electron and neutral recoil trajectories. The effects of trapping parameters on the center-of-mass trajectories in the laser-ion interaction region are explored to optimize neutral particle resolution, and the impact of bunching on ion oscillation is established. Finally, an initial demonstration of radiative cooling is presented. PMID- 22047328 TI - Development of the heat treatment system for the 40 T hybrid magnet superconducting outsert. AB - The heat treatment of Nb(3)Sn coil with the glass fabric insulation is one of the key and critical processes for the outsert solenoids of the 40 T hybrid magnet, which could be wound with cable-in-conduit conductors using the insulation-wind and-react technique. The manufacturing of the large vertical type vacuum/Ar atmosphere-protection heat treatment system has been completed and recently installed in the High Magnetic Filed Laboratory, Chinese Academy of Sciences. The heat treatment system composed mainly the furnace, the purging gas supply system, the control system, the gas impurities monitoring system, and so on. At present, the regulation and testing of the heat treatment system has been successfully finished, and all of technical parameters meet or exceed specifications. PMID- 22047329 TI - A design of backing seat and gasket assembly in diamond anvil cell for accurate single crystal x-ray diffraction to 5 GPa. AB - We designed a new cell assembly of diamond anvil cells for single crystal x-ray diffraction under pressure and demonstrate the application of the cell to the crystallographic studies for ice VI and ethanol high-pressure (HP) phase at 0.95(5) GPa and 1.95(2) GPa, respectively. The features of the assembly are: (1) the platy anvil and unique-shaped backing seat (called as "Wing seat") allowing the extremely wide opening angle up to +/-65 degrees , (2) the PFA-bulk metallic glass composite gasket allowing the easy attenuation correction and less background. Thanks to the designed assembly, the R(int) values after attenuation corrections are fairly good (0.0125 and 0.0460 for ice VI and ethanol HP phase, respectively), and the errors of the refined parameters are satisfactory small even for hydrogen positions, those are comparable to the results which obtained at ambient conditions. The result for ice VI is in excellent agreement with the previous study, and that for ethanol HP phase has remarkable contributions to the revision to its structure; the H12 site, which makes gauche molecules with O1, C2, and C3 sites, may not exist so that only trans conformers are present at least at 1.95(2) GPa. The accurate intensities using the cell assembly allow us to extract the electron density for ethanol HP phase by the maximum entropy method. PMID- 22047330 TI - Compact x-ray microradiograph for in situ imaging of solidification processes: bringing in situ x-ray micro-imaging from the synchrotron to the laboratory. AB - A laboratory based high resolution x-ray radiograph was developed for the investigation of solidification dynamics in alloys. It is based on a low-power microfocus x-ray tube and is potentially appropriate for x-ray diagnostics in space. The x-ray microscope offers a high spatial resolution down to approximately 5 MUm. Dynamic processes can be resolved with a frequency of up to 6 Hz. In reference experiments, the setup was optimized to yield a high contrast for AlCu-alloys. With samples of about 150 MUm thickness, high quality image sequences of the solidification process were obtained with high resolution in time and space. PMID- 22047331 TI - Cryogenic implementation of charging diamond anvil cells with H2 and D2. AB - A cryogenic loading system for introducing H(2) and D(2) into the diamond anvil cell has been designed and constructed. The integration of pressure loading mechanism, ruby fluorescence spectrometer, and microscope camera allows for in situ tuning and calibrating the pressure. The performance of the system has been demonstrated by successful synthesis of hydride and deuteride of transition metal and rare earth metal. Our cryogenic methodology features facile start-over of loading and in situ electrical resistance measurement of as-synthesized sample. PMID- 22047332 TI - Fast template tracking in video sequences. AB - Tracking of poorly defined, rotating and/or distorted objects in a video sequence poses significant problems especially in medical diagnostics including ultrasound (sonographic) video used for examination and diagnosis of internal movement of tissue or muscle and nerve action. Cross-correlation techniques have been successful in retrieving dynamic information directly from ultrasound video data. We outline a fast implementation of tracking based on normalized cross correlation using an adaptive template and present results from our application, developed in MATLABTM, which successfully tracks arbitrarily selected objects in deformed or severely compromised images. Common ultrasound image evaluation is qualitative but there is need to retrieve quantitative dynamic information such as the trajectory or velocity of selected areas. Our approach uses normalized two dimensional cross-correlation to find the position of an initially selected template enclosing the feature of interest and map its trajectory frame-by-frame to produce displacement and velocity plots. We illustrate operation of the application using routine ultrasound data and demonstrate its performance using test video of objects rotating full circle and rolling down a ramp. We analyse errors associated with sampling to compare performance of our implementation with a more rigorous but tedious and computationally expensive correlation of a resampled, rotated, and shifted template. PMID- 22047333 TI - Analysis of the particle stability in a new designed ultrasonic levitation device. AB - The use of acoustic levitation in the fields of analytical chemistry and in the containerless processing of materials requires a good stability of the levitated particle. However, spontaneous oscillations and rotation of the levitated particle have been reported in literature, which can reduce the applicability of the acoustic levitation technique. Aiming to reduce the particle oscillations, this paper presents the analysis of the particle stability in a new acoustic levitator device. The new acoustic levitator consists of a piezoelectric transducer with a concave radiating surface and a concave reflector. The analysis is conducted by determining numerically the axial and lateral forces that act on the levitated object and by measuring the oscillations of a sphere particle by a laser Doppler vibrometer. It is shown that the new levitator design allows to increase the lateral forces and reduce significantly the lateral oscillations of the levitated object. PMID- 22047334 TI - Expanded beam deflection method for simultaneous measurement of displacement and vibrations of multiple microcantilevers. AB - Here we present an extension of optical beam deflection (OBD) method for measuring displacement and vibrations of an array of microcantilevers. Instead of focusing on the cantilever, the optical beam is either focused above or below the cantilever array, or focused only in the axis parallel to the cantilevers length, allowing a wide optical line to span multiple cantilevers in the array. Each cantilever reflects a part of the incident beam, which is then directed onto a photodiode array detector in a manner allowing distinguishing between individual beams. Each part of reflected beam behaves like a single beam of roughly the same divergence angle in the bending sensing axis as the incident beam. Since sensitivity of the OBD method depends on the divergence angle of deflected beam, high sensitivity is preserved in proposed expanded beam deflection (EBD) method. At the detector, each spot's position is measured at the same time, without time multiplexing of light sources. This provides real simultaneous readout of entire array, unavailable in most of competitive methods, and thus increases time resolution of the measurement. Expanded beam can also span another line of cantilevers allowing monitoring of specially designed two-dimensional arrays. In this paper, we present first results of application of EBD method to cantilever sensors. We show how thermal noise resolution can be easily achieved and combined with thermal noise based resonance frequency measurement. PMID- 22047335 TI - Optimization of a vacuum chamber for vibration measurements. AB - A 200 degrees C high vacuum chamber has been built to improve vibration measurement sensitivity. The optimized design addresses two significant issues: (i) vibration measurements under high vacuum conditions and (ii) use of design optimization tools to reduce operating costs. A test rig consisting of a cylindrical vessel with one access port has been constructed with a welded bellows assembly used to seal the vessel and enable vibration measurements in high vacuum that are comparable with measurements in air. The welded-bellows assembly provides a force transmissibility of 0.1 or better at 15 Hz excitation under high vacuum conditions. Numerical results based on design optimization of a larger diameter chamber are presented. The general constraints on the new design include material yield stress, chamber first natural frequency, vibration isolation performance, and forced convection heat transfer capabilities over the exterior of the vessel access ports. Operating costs of the new chamber are reduced by 50% compared to a preexisting chamber of similar size and function. PMID- 22047336 TI - A magnetically driven piston pump for ultra-clean applications. AB - A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon time projection chamber of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute of xenon gas with 750 Torr differential pressure. PMID- 22047337 TI - Elastic incoherent neutron scattering operating by varying instrumental energy resolution: principle, simulations, and experiments of the resolution elastic neutron scattering (RENS). AB - The main aim of this paper is to present the scientific case of the resolution elastic neutron scattering (RENS) method that is based on the collection of elastic neutron scattering intensity as a function of the instrumental energy resolution and that is able to extract information on the system dynamical properties from an elastic signal. In this framework, it is shown that in the measured elastic scattering law, as a function of the instrumental energy resolution, an inflection point occurs when the instrumental energy resolution intersects the system relaxation time, and in an equivalent way, a transition in the temperature behavior of the measured elastic scattering law occurs when the characteristic system relaxation time crosses the instrumental energy resolution time. With regard to the latter, an operative protocol to determine the system characteristic time by different elastic incoherent neutron scattering (EINS) thermal scans at different instrumental energy resolutions is also proposed. The proposed method, hence, is not primarily addressed to collect the measured elastic scattering intensity with a great accuracy, but rather relies on determining an inflection point in the measured elastic scattering law versus instrumental energy resolution. The RENS method is tested both numerically and experimentally. As far as numerical simulations are concerned, a simple model system for which the temperature behavior of the relaxation time follows an Arrhenius law, while its scattering law follows a Gaussian behavior, is considered. It is shown that the system relaxation time used as an input for the simulations coincides with the one obtained by the RENS approach. Regarding the experimental findings, due to the fact that a neutron scattering spectrometer working following the RENS method has not been constructed yet, different EINS experiments with different instrumental energy resolutions were carried out on a complex model system, i.e., dry and D(2)O hydrated lysozyme, in an extended temperature range. The resulting temperature behavior of the system relaxation time, obtained with RENS method, agrees very well with the one obtained in literature, for the same system, following the quasi-elastic neutron scattering (QENS) approach. The proposed scientific case puts into evidence the challenges of an RENS spectrometer working by varying the instrumental energy resolution; in particular, in comparison with QENS, the proposed RENS method requires a smaller amount of sample, which is an important point in dealing with biological and exotic systems; it is not affected by the use of model functions for fitting spectra as in QENS, but furnishes a direct access to relevant information. PMID- 22047338 TI - A generalized analytical compliance model for transversely symmetric three segment flexure hinges. AB - This paper presents a generalized compliance model for a three-segment notch flexure hinge with transverse symmetry. This flexure hinge configuration is most frequently employed in planar-motion, small-displacement compliant mechanisms. The axial and bending compliances are derived for this flexure hinge based on the compliances of two flexure components. The derivation is generalized such that it can be applied to various segment geometries. Using this open-ended model, a three-segment right elliptical corner-filleted flexure hinge design was analyzed. This geometric configuration introduces additional geometric parameters, which can be used to optimize the compliance of the flexure hinge without modifying its gross dimensions. The results of the analysis were validated in part by modifying the geometric parameters of the center segment and elliptical corner fillets to form limiting cases corresponding to several previously investigated configurations, namely right elliptical, three-segment right circular corner filleted, and right circular geometries. Finite element analysis simulation and experimental testing were used to further validate the three-segment right elliptical corner-filleted analytical model. Additional simulations based on the analytical model were performed to highlight the influence of geometric parameters on compliances and to investigate shear effects for short flexure hinges. PMID- 22047339 TI - Note: Simultaneous electrical and optical detection of expanding dense partially ionized vapour clouds. AB - The scheme and construction of an electro-optical probe able to collect charge and detect optical emission from expanding dense partially ionized vapour clouds are reported. The instrument can be applied to phenomena such as dust impact ionization and solid target laser ablation. First, results of measurements of expanding plasma cloud formed upon ablating W target are presented. Use of the instrument in different experimental facilities, including tokamak, is discussed. PMID- 22047340 TI - Note: A novel method for in situ loading of gases via x-ray induced chemistry. AB - We have developed and demonstrated a novel method to load oxygen in a sealed diamond anvil cell via the x-ray induced decomposition of potassium chlorate. By irradiating a pressurized sample of an oxidizer (KClO(3)) with either monochromatic or white beam x-rays from the Advanced Photon Source at ambient temperature and variable pressure, we succeeded in creating a localized region of molecular oxygen surrounded by unreacted sample which was confirmed via Raman spectroscopy. We anticipate that this technique will be useful in loading even more challenging, difficult-to-load gases such as hydrogen and also to load multiple gases. PMID- 22047341 TI - Note: Compact high voltage pulse transformer made using a capacitor bank assembled in the shape of primary. AB - The experimental results of an air-core pulse transformer are presented, which is very compact (<10 Kg in weight) and is primed by a capacitor bank that is fabricated in such a way that the capacitor bank with its switch takes the shape of single-turn rectangular shaped primary of the transformer. A high voltage capacitor assembly (pulse-forming-line capacitor, PFL) of 5.1 nF is connected with the secondary of transformer. The transformer output voltage is 160 kV in its second peak appearing in less than 2 MUS from the beginning of the capacitor discharge. The primary capacitor bank can be charged up to a maximum of 18 kV, with the voltage delivery of 360 kV in similar capacitive loads. PMID- 22047342 TI - Note: Recent achievements at the 60-MeV linac for sub-picosecond terahertz radiation at the Pohang Accelerator Laboratory. AB - A femtosecond (fs) terahertz (THz) linac has been constructed to generate fs-THz radiation by using ultrashort electron beam at the Pohang Accelerator Laboratory. To generate an ultrashort electron beam with 60-MeV energy, a chicane bunch compressor has been adopted. Simulation studies have been conducted to design the linac. In this note, recent achievements at 60-MeV linac are presented. PMID- 22047343 TI - Note: Mechanical and electrical characterization of nanowires in scanning electron microscope. AB - This note presents two experimental techniques for mechanical and electrical characterization of individual nanowires inside a scanning electron microscope (SEM). Tensile testing is realized by transferring a nanowire to a microelectromechanical systems device that stretches the nanowire and measures the elongations and tensile forces. The device consists of an electrostatic actuator and two capacitive sensors, capable of acquiring all measurement data (force and displacement) electronically without relying on electron microscopy imaging. For electrical characterization, four-point probe measurement of individual nanowires is performed automatically by controlling four nanomanipulators with SEM visual feedback. A feedforward controller is incorporated into the control system to improve the response time. This work represents advances in nanomaterial testing and automated nanomanipulation. PMID- 22047344 TI - Note: Continuing improvements on the novel flat-response x-ray detector. AB - This note describes multi-updates of the novel flat-response x-ray detector in fabrication technology, experimental application, and data uncertainty evaluation. Unlike the previous design, the compound filter is combined into one piece through an improved fabrication process that greatly enhanced its self supporting capability. A method of pinhole-array imaging is introduced into the experimental application process to stop any debris from the hohlraum and to uniformly reduce the radiation flux. The experimental results show that this method works well. Furthermore, a method of uncertainty evaluation of the radiation flux measurement by the novel flat-response x-ray detector has been developed. The influence of the radiation spectrum to the flux measurement is analyzed. The evaluation shows that the relative uncertainty of the radiation flux is about 10% in higher radiation temperature condition (Tr > 150 eV) and 16% in lower radiation temperature condition (Tr < 100 eV). PMID- 22047346 TI - Point/Counterpoint: QA procedures in radiation therapy are outdated and negatively impact the reduction of errors. PMID- 22047347 TI - Interfraction patient motion and implant displacement in prostate high dose rate brachytherapy. AB - PURPOSE: To quantify movement of prostate cancer patients undergoing treatment, using an in-house developed motion sensor in order to determine a relationship between patient movement and high dose rate (HDR) brachytherapy implant displacement. METHODS: An electronic motion sensor was developed based on a three axis accelerometer. HDR brachytherapy treatment for prostate is delivered at this institution in two fractions 24 h apart and 22 patients were monitored for movement over the interval between fractions. The motion sensors functioned as inclinometers, monitoring inclination of both thighs, and the inclination and roll of the abdomen. The implanted HDR brachytherapy catheter set was assessed for displacement relative to fiducial markers in the prostate. Angle measurements and angle differences over a 2 s time base were binned, and the standard deviations of the resulting frequency distributions used as a metric for patient motion in each monitored axis. These parameters were correlated to measured catheter displacement using regression modeling. RESULTS: The mean implant displacement was 12.6 mm in the caudal direction. A mean of 19.95 h data was recorded for the patient cohort. Patients generally moved through a limited range of angles with a mean of the exception of two patients who spent in excess of 2 h lying on their side. When tested for a relationship between movement in any of the four monitored axes and the implant displacement, none was significant. CONCLUSIONS: It is not likely that patient movement influences HDR prostate implant displacement. There may be benefits to patient comfort if nursing protocols were relaxed to allow patients greater freedom to move while the implant is in situ. PMID- 22047348 TI - On the role of the optimization algorithm of RapidArc((r)) volumetric modulated arc therapy on plan quality and efficiency. AB - PURPOSE: The RapidArc volumetric modulated arc therapy (VMAT) planning process is based on a core engine, the so-called progressive resolution optimizer (PRO). This is the optimization algorithm used to determine the combination of field shapes, segment weights (with dose rate and gantry speed variations), which best approximate the desired dose distribution in the inverse planning problem. A study was performed to assess the behavior of two versions of PRO. These two versions mostly differ in the way continuous variables describing the modulated arc are sampled into discrete control points, in the planning efficiency and in the presence of some new features. The analysis aimed to assess (i) plan quality, (ii) technical delivery aspects, (iii) agreement between delivery and calculations, and (iv) planning efficiency of the two versions. METHODS: RapidArc plans were generated for four groups of patients (five patients each): anal canal, advanced lung, head and neck, and multiple brain metastases and were designed to test different levels of planning complexity and anatomical features. Plans from optimization with PRO2 (first generation of RapidArc optimizer) were compared against PRO3 (second generation of the algorithm). Additional plans were optimized with PRO3 using new features: the jaw tracking, the intermediate dose and the air cavity correction options. RESULTS: Results showed that (i) plan quality was generally improved with PRO3 and, although not for all parameters, some of the scored indices showed a macroscopic improvement with PRO3. (ii) PRO3 optimization leads to simpler patterns of the dynamic parameters particularly for dose rate. (iii) No differences were observed between the two algorithms in terms of pretreatment quality assurance measurements and (iv) PRO3 optimization was generally faster, with a time reduction of a factor approximately 3.5 with respect to PRO2. CONCLUSIONS: These results indicate that PRO3 is either clinically beneficial or neutral in terms of dosimetric quality while it showed significant advantages in speed and technical aspects. PMID- 22047349 TI - Evaluation of brachytherapy lung implant dose distributions from photon-emitting sources due to tissue heterogeneities. AB - PURPOSE: Photon-emitting brachytherapy sources are used for permanent implantation to treat lung cancer. However, the current brachytherapy dose calculation formalism assumes a homogeneous water medium without considering the influence of radiation scatter or tissue heterogeneities. The purpose of this study was to determine the dosimetric effects of tissue heterogeneities for permanent lung brachytherapy. METHODS: The MCNP5 v1.40 radiation transport code was used for Monte Carlo (MC) simulations. Point sources with energies of 0.02, 0.03, 0.05, 0.1, 0.2, and 0.4 MeV were simulated to cover the range of pertinent brachytherapy energies and to glean dosimetric trends independent of specific radionuclide emissions. Source positions from postimplant CT scans of five patient implants were used for source coordinates, with dose normalized to 200 Gy at the center of each implant. With the presence of fibrosis (around the implant), cortical bone, lung, and healthy tissues, dose distributions and (PTV)DVH were calculated using the MCNP *FMESH4 tally and the NIST mass-energy absorption coefficients. This process was repeated upon replacing all tissues with water. For all photon energies, 10(9) histories were simulated to achieve statistical errors (k = 1) typically of 1%. RESULTS: The mean PTV doses calculated using tissue heterogeneities for all five patients changed (compared to dose to water) by only a few percent over the examined photon energy range, as did PTV dose at the implant center. The (PTV)V(100) values were 81.2%, 90.0% (as normalized), 94.3%, 93.9%, 92.7%, and 92.2% for 0.02, 0.03, 0.05, 0.1, 0.2, and 0.4 MeV source photons, respectively. Relative to water, the maximum bone doses were higher by factors of 3.7, 5.1, 5.2, 2.4, 1.2, and 1.0 The maximum lung doses were about 0.98, 0.94, 0.91, 0.94, 0.97, and 0.99. Relative to water, the maximum healthy tissue doses at the mediastinal position were higher by factors of 9.8, 2.2, 1.3, 1.1, 1.1, and 1.1. However, the maximum doses to these healthy tissues were only 3.1, 7.2, 11.3, 10.9, 9.0, and 8.1 Gy while maximum bone doses were 66, 177, 236, 106, 49, and 39 Gy, respectively. Similarly, maximum lung doses were 55, 66, 73, 74, 73, and 73 Gy, respectively. CONCLUSIONS: The current brachytherapy dose calculation formalism overestimates PTV dose and significantly underestimates doses to bone and healthy tissue. Further investigation using specific brachytherapy source models and patient-based CT datasets as MC input may indicate whether the observed trends can be generalized for low-energy lung brachytherapy dosimetry. PMID- 22047350 TI - Evaluation of volumetric modulated arc therapy for cranial radiosurgery using multiple noncoplanar arcs. AB - PURPOSE: To evaluate a commercial volumetric modulated arc therapy (VMAT), using multiple noncoplanar arcs, for linac-based cranial radiosurgery, as well as evaluate the combined accuracy of the VMAT dose calculations and delivery. METHODS: Twelve patients with cranial lesions of variable size (0.1-29 cc) and two multiple metastases patients were planned (Eclipse RapidArc AAA algorithm, v8.6.15) using VMAT (1-6 noncoplanar arcs), dynamic conformal arc (DCA, ~4 arcs), and IMRT (nine static fields). All plans were evaluated according to a conformity index (CI), healthy brain tissue doses and volumes, and the dose to organs at risk. A 2D dose distribution was measured (Varian Novalis Tx, HD120 MLC, 1000 MU/min, 6 MV beam) for the ~4 arc VMAT treatment plans using calibrated film dosimetry. RESULTS: The CI (0-1 best) average for all plans was best for ~4 noncoplanar arc VMAT at 0.86 compared with ~0.78 for IMRT and a single arc VMAT and 0.68 for DCA. The volumes of healthy brain receiving 50% of the prescribed target coverage dose or more (V(50%)) were lowest for the four arc VMAT [RA(4)] and DCA plans. The average ratio of the V(50%) for the other plans to the RA(4) V(50%) were 1.9 for a single noncoplanar arc VMAT [RA(1nc)], 1.4 for single full coplanar arc VMAT [RA(1f)] and 1.3 for IMRT. The V(50%) improved significantly for single isocenter multiple metastases plan when two noncoplanar VMAT arcs were added to a full single coplanar one. The maximum dose to 5 cc of the outer 1 cm rim of healthy brain which one may want to keep below nonconsequential doses of 300-400 cGy, was 2-3 times greater for IMRT, RA(1nc) and RA(1f) plans compared with the multiple noncoplanar arc DCA and RA(4) techniques. Organs at risk near (0-4 mm) to targets were best spared by (i) single noncoplanar arcs when the targets are lateral to the organ at risk and (ii) by skewed nonvertical planes of IMRT fields when the targets are not lateral to the organ at risk. The highest dose gradient observed between an organ at risk and a target at the edge of a VMAT arc plane or plane of IMRT fields was 17%/mm. The average absolute percent difference between the measured and calculated central axis dose for all the VMAT plans was 3.6 +/- 2.2%. The measured perpendicular profile widths and shifts were on average within 0.5 mm of planned values. The average total MUs for VMAT plans was double the DCA average and similar to the IMRT average. CONCLUSIONS: For the aforementioned planning and delivery system and cranial lesions greater than 7 mm in diameter, multiple noncoplanar arc VMAT consistently provides accurate and high quality cranial radiosurgery dose distributions with low doses to healthy brain tissue and high dose conformity to the target. These qualities may make multiple noncoplanar arc VMAT suitable for a greater range of prescription doses or larger and more irregular lesions. For smaller and/or rounder lesions there are other clinically acceptable treatment techniques that may involve fewer couch angles or arcs and reduce treatment times. PMID- 22047351 TI - A handheld fluorescence molecular tomography system for intraoperative optical imaging of tumor margins. AB - PURPOSE: Accurate identification of tumor margins presents a major challenge in the surgical treatment of human cancers. Inability of complete removal of tumor lesions after surgery causes local recurrence and increases the incidence of developing tumor metastasis. It is clear that novel approaches that allow defining tumor margins intraoperatively for removal of small tumor lesions in the surgical cavity is critical for improving prognosis of cancer patients. To facilitate image-guided surgery using targeted optical imaging probes, we have developed a reflection-mode fluorescence molecular tomography (FMT) system with a handheld probe that is able to provide three-dimensional tumor margin information. METHODS: The imaging method and system were validated using both simulated and phantom experiments. We further examined the accuracy of the handheld FMT system in an orthotopic mouse mammary tumor model following systemic delivery of near-infrared (NIR) dye-labeled and urokinase plasminogen activator receptor targeted magnet iron oxide nanoparticles. RESULTS: Our results show that when the targets are located within 5 mm beneath the surface of the media, fluorescent images can be reliably detected and reconstructed with an average positional error of 0.5 mm laterally and 1.5 mm axially. For in vivo imaging in the mouse tumor model, the location and size of the tumor detected by FMT correlated well with that measured by the magnetic resonance imaging (MRI). CONCLUSIONS: Our system can three-dimensionally image targets located at a depth of up to 7 mm. The in vivo results suggest that in combination with targeted optical imaging probes, this handheld FMT system can be potentially used as an intraoperative tool for the detection of tumor margins and for image-guided surgery. PMID- 22047352 TI - Automated temporal tracking and segmentation of lymphoma on serial CT examinations. AB - PURPOSE: It is challenging to reproducibly measure and compare cancer lesions on numerous follow-up studies; the process is time-consuming and error-prone. In this paper, we show a method to automatically and reproducibly identify and segment abnormal lymph nodes in serial computed tomography (CT) exams. METHODS: Our method leverages initial identification of enlarged (abnormal) lymph nodes in the baseline scan. We then identify an approximate region for the node in the follow-up scans using nonrigid image registration. The baseline scan is also used to locate regions of normal, non-nodal tissue surrounding the lymph node and to map them onto the follow-up scans, in order to reduce the search space to locate the lymph node on the follow-up scans. Adaptive region-growing and clustering algorithms are then used to obtain the final contours for segmentation. We applied our method to 24 distinct enlarged lymph nodes at multiple time points from 14 patients. The scan at the earlier time point was used as the baseline scan to be used in evaluating the follow-up scan, resulting in 70 total test cases (e.g., a series of scans obtained at 4 time points results in 3 test cases). For each of the 70 cases, a "reference standard" was obtained by manual segmentation by a radiologist. Assessment according to response evaluation criteria in solid tumors (RECIST) using our method agreed with RECIST assessments made using the reference standard segmentations in all test cases, and by calculating node overlap ratio and Hausdorff distance between the computer and radiologist-generated contours. RESULTS: Compared to the reference standard, our method made the correct RECIST assessment for all 70 cases. The average overlap ratio was 80.7 +/- 9.7% s.d., and the average Hausdorff distance was 3.2 +/- 1.8 mm s.d. The concordance correlation between automated and manual segmentations was 0.978 (95% confidence interval 0.962, 0.984). The 100% agreement in our sample between our method and the standard with regard to RECIST classification suggests that the true disagreement rate is no more than 6%. CONCLUSIONS: Our automated lymph node segmentation method achieves excellent overall segmentation performance and provides equivalent RECIST assessment. It potentially will be useful to streamline and improve cancer lesion measurement and tracking and to improve assessment of cancer treatment response. PMID- 22047353 TI - A PENELOPE-based system for the automated Monte Carlo simulation of clinacs and voxelized geometries-application to far-from-axis fields. AB - PURPOSE: Two new codes, PENEASY and PENEASYLINAC, which automate the Monte Carlo simulation of Varian Clinacs of the 600, 1800, 2100, and 2300 series, together with their electron applicators and multileaf collimators, are introduced. The challenging case of a relatively small and far-from-axis field has been studied with these tools. METHODS: PENEASY is a modular, general-purpose main program for the PENELOPE Monte Carlo system that includes various source models, tallies and variance-reduction techniques (VRT). The code includes a new geometry model that allows the superposition of voxels and objects limited by quadric surfaces. A variant of the VRT known as particle splitting, called fan splitting, is also introduced. PENEASYLINAC, in turn, automatically generates detailed geometry and configuration files to simulate linacs with PENEASY. These tools are applied to the generation of phase-space files, and of the corresponding absorbed dose distributions in water, for two 6 MV photon beams from a Varian Clinac 2100 C/D: a 40 * 40 cm(2) centered field; and a 3 * 5 cm(2) field centered at (4.5, -11.5) cm from the beam central axis. This latter configuration implies the largest possible over-traveling values of two of the jaws. Simulation results for the depth dose and lateral profiles at various depths are compared, by using the gamma index, with experimental values obtained with a PTW 31002 ionization chamber. The contribution of several VRTs to the computing speed of the more demanding off-axis case is analyzed. RESULTS: For the 40 * 40 cm(2) field, the percentages gamma(1) and gamma(1.2) of voxels with gamma indices (using 0.2 cm and 2% criteria) larger than unity and larger than 1.2 are 0.2% and 0%, respectively. For the 3 * 5 cm(2) field, gamma(1) = 0%. These figures indicate an excellent agreement between simulation and experiment. The dose distribution for the off-axis case with voxels of 2.5 * 2.5 * 2.5 mm(3) and an average standard statistical uncertainty of 2% (1sigma) is computed in 3.1 h on a single core of a 2.8 GHz Intel Core 2 Duo processor. This result is obtained with the optimal combination of the tested VRTs. In particular, fan splitting for the off-axis case accelerates execution by a factor of 240 with respect to standard particle splitting. CONCLUSIONS: PENEASY and PENEASYLINAC can simulate the considered Varian Clinacs both in an accurate and efficient manner. Fan splitting is crucial to achieve simulation results for the off-axis field in an affordable amount of CPU time. Work to include Elekta linacs and to develop a graphical interface that will facilitate user input is underway. PMID- 22047354 TI - Three-dimensional anisotropic adaptive filtering of projection data for noise reduction in cone beam CT. AB - PURPOSE: The combination of quickly rotating C-arm gantry with digital flat panel has enabled the acquisition of three-dimensional data (3D) in the interventional suite. However, image quality is still somewhat limited since the hardware has not been optimized for CT imaging. Adaptive anisotropic filtering has the ability to improve image quality by reducing the noise level and therewith the radiation dose without introducing noticeable blurring. By applying the filtering prior to 3D reconstruction, noise-induced streak artifacts are reduced as compared to processing in the image domain. METHODS: 3D anisotropic adaptive filtering was used to process an ensemble of 2D x-ray views acquired along a circular trajectory around an object. After arranging the input data into a 3D space (2D projections + angle), the orientation of structures was estimated using a set of differently oriented filters. The resulting tensor representation of local orientation was utilized to control the anisotropic filtering. Low-pass filtering is applied only along structures to maintain high spatial frequency components perpendicular to these. The evaluation of the proposed algorithm includes numerical simulations, phantom experiments, and in-vivo data which were acquired using an AXIOM Artis dTA C-arm system (Siemens AG, Healthcare Sector, Forchheim, Germany). Spatial resolution and noise levels were compared with and without adaptive filtering. A human observer study was carried out to evaluate low contrast detectability. RESULTS: The adaptive anisotropic filtering algorithm was found to significantly improve low-contrast detectability by reducing the noise level by half (reduction of the standard deviation in certain areas from 74 to 30 HU). Virtually no degradation of high contrast spatial resolution was observed in the modulation transfer function (MTF) analysis. Although the algorithm is computationally intensive, hardware acceleration using Nvidia's CUDA Interface provided an 8.9-fold speed-up of the processing (from 1336 to 150 s). CONCLUSIONS: Adaptive anisotropic filtering has the potential to substantially improve image quality and/or reduce the radiation dose required for obtaining 3D image data using cone beam CT. PMID- 22047355 TI - Development of a prototype gantry system for preclinical x-ray phase-contrast computed tomography. AB - PURPOSE: To explore the potential of grating-based x-ray phase-contrast imaging for clinical applications, a first compact gantry system was developed. It is designed such that it can be implemented into an in-vivo small-animal phase contrast computed tomography (PC-CT) scanner. The purpose of the present study is to assess the accuracy and quantitativeness of the described gantry in both absorption and phase-contrast. METHODS: A phantom, containing six chemically well defined liquids, was constructed. A tomography scan with cone-beam reconstruction of this phantom was performed yielding the spatial distribution of the linear attenuation coefficient MU and decrement delta of the complex refractive index. Theoretical values of MU and delta were calculated for each liquid from tabulated data and compared with the experimentally measured values. Additionally, a color fused image representation is proposed to display the complementary absorption and phase-contrast information in a single image. RESULTS: Experimental and calculated data of the phantom agree well confirming the quantitativeness and accuracy of the reconstructed spatial distributions of MU and delta. The proposed color-fused image representation, which combines the complementary absorption and phase information, considerably helps in distinguishing the individual substances. CONCLUSIONS: The concept of grating-based phase-contrast computed tomography (CT) can be implemented into a compact, cone-beam geometry gantry setup. The authors believe that this work represents an important milestone in translating phase-contrast x-ray imaging from previous proof-of-principle experiments to first preclinical biomedical imaging applications on small-animal models. PMID- 22047356 TI - Technical note: further development of a resolution modification routine for the simulation of the modulation transfer function of digital x-ray detectors. AB - PURPOSE: This paper proposes the further development of a resolution modification routine which is used to simulate the presampling modulation transfer function (pMTF) of digital x-ray detectors. METHODS: It suggests a method to reconstruct anisotropic two dimensional (2D) pMTF matrices from the experimentally measured horizontal and vertical 1D pMTFs. In this study, the horizontal dimension of the detector is 17.3 cm, while the vertical one is 24 cm. This matrix is multiplied with the 2D Fourier transform of the super-sampled ideal input image to simulate blurring. Then, the restored image is sampled to form the pixels of the digital image. The authors suggest convolution with the comb function instead of the rectangular function to avoid the correction with the sinc function required by the latter. It is demonstrated that this correction is avoided when the comb function is used. Moreover, this study suggests a way to effectively sample the images in the case when the ratio between the "analog" pitch of the super-sampled input image and the pixel pitch of the digital x-ray detector is a semi-integer. RESULTS: The validation of the simulation algorithm demonstrated that when the comb function was used the average absolute difference between the pMTF measured from the output images and the input ones was less than 1%, while this was of 13% when the rectangular function was used. When a sinc correction was applied in the latter case the difference decreased again to less than 1%. CONCLUSIONS: The developed modification routine provides the means to simulate the spatial resolution of digital x-ray detectors under a wider range of conditions. PMID- 22047357 TI - Improving accuracy of XRII image distortion correction using a new hybrid image processing method: performance assessment. AB - PURPOSE: Improving accuracy in x-ray image intensifier (XRII) image distortion correction has clinical impact in order to apply XRII images in a variety of clinical applications more reliably. This study aimed to develop and evaluate a new hybrid mathematic approximation method to correct geometric distortions of XRII images. METHODS: The proposed hybrid method integrated an MLS (moving least squares method) and an MBA (multilevel B-spline approximation) approach (MLSMBA). In the hybrid method, MLS is used to generate denser "virtual" data points on the basis of sparse original data points; MBA is applied to approximate an ultimate mapping function based on the generated and original data points. Using both computer-simulated and real XRII images, the authors compared the image distortion correction accuracy of the proposed method with those yielded using a number of previously developed and currently routinely used methods. The comparison methods include the traditional local and global approximation methods, an approach combining both local and global approximation methods, and an author's previously developed hybrid method by integrating MLS followed by another traditional least-square approximation (MLSILS). The image distortion correction accuracy was evaluated using mean-squared residual errors measured at control and intermediate points. In addition, the impact of pincushion distortion, sigmoidal distortion, local distortion, and control point localization errors on these methods was tested using computer-simulated image data. RESULTS: The experimental results using the computer-simulated data showed that unlike the traditional local and global approximation methods that are quite sensitive to pincushion and/or sigmoidal distortion, the MLSMBA method was insensitive to these two types of common distortion depicted in XRII images. Similar to the MLSILS method, sensitivity of MLSMBA to local distortion was lower than or comparable with that of the traditional global approximation method. Although sensitivity of MLSMBA to control point localization errors was higher than that of the global approximation method, as long as the standard deviation of pixel displacement errors was smaller than 0.1 pixels, the overall distortion correction accuracy of MLSMBA remains higher than that of the other methods. By selecting a proper cutoff radius, accuracy of MLSMBA is also higher than that of the other methods (including MLSILS). Experiments on real XRII images yielded similar results. For example, processing results using one XRII image showed that residual error (0.248 +/- 0.236 pixels) of MLSMBA was smallest as compared to that of the other methods, including two local approximation methods (0.456 +/- 0.352 pixels and 0.370 +/- 0.402 pixels), a global approximation method (0.422 +/ 0.388 pixels), an approach combining local and global methods (0.389 +/- 0.386 pixels), and MLSILS (0.255 +/- 0.248 pixels). CONCLUSIONS: The MLSMBA method could be a better choice to correct geometric distortion of raw XRII images in the following conditions: (1) pincushion distortion, sigmoidal distortion, and local distortion exist simultaneously in the XRII images, (2) the number of original control points (landmarks) is limited, and (3) reusability of the correction mapping function is required. PMID- 22047358 TI - An adaptive regularization parameter choice strategy for multispectral bioluminescence tomography. AB - PURPOSE: Bioluminescence tomography (BLT) provides an effective tool for monitoring physiological and pathological activities in vivo. However, the measured data in bioluminescence imaging are corrupted by noise. Therefore, regularization methods are commonly used to find a regularized solution. Nevertheless, for the quality of the reconstructed bioluminescent source obtained by regularization methods, the choice of the regularization parameters is crucial. To date, the selection of regularization parameters remains challenging. With regards to the above problems, the authors proposed a BLT reconstruction algorithm with an adaptive parameter choice rule. METHODS: The proposed reconstruction algorithm uses a diffusion equation for modeling the bioluminescent photon transport. The diffusion equation is solved with a finite element method. Computed tomography (CT) images provide anatomical information regarding the geometry of the small animal and its internal organs. To reduce the ill-posedness of BLT, spectral information and the optimal permissible source region are employed. Then, the relationship between the unknown source distribution and multiview and multispectral boundary measurements is established based on the finite element method and the optimal permissible source region. Since the measured data are noisy, the BLT reconstruction is formulated as l(2) data fidelity and a general regularization term. When choosing the regularization parameters for BLT, an efficient model function approach is proposed, which does not require knowledge of the noise level. This approach only requests the computation of the residual and regularized solution norm. With this knowledge, we construct the model function to approximate the objective function, and the regularization parameter is updated iteratively. RESULTS: First, the micro-CT based mouse phantom was used for simulation verification. Simulation experiments were used to illustrate why multispectral data were used rather than monochromatic data. Furthermore, the study conducted using an adaptive regularization parameter demonstrated our ability to accurately localize the bioluminescent source. With the adaptively estimated regularization parameter, the reconstructed center position of the source was (20.37, 31.05, 12.95) mm, and the distance to the real source was 0.63 mm. The results of the dual-source experiments further showed that our algorithm could localize the bioluminescent sources accurately. The authors then presented experimental evidence that the proposed algorithm exhibited its calculated efficiency over the heuristic method. The effectiveness of the new algorithm was also confirmed by comparing it with the L-curve method. Furthermore, various initial speculations regarding the regularization parameter were used to illustrate the convergence of our algorithm. Finally, in vivo mouse experiment further illustrates the effectiveness of the proposed algorithm. CONCLUSIONS: Utilizing numerical, physical phantom and in vivo examples, we demonstrated that the bioluminescent sources could be reconstructed accurately with automatic regularization parameters. The proposed algorithm exhibited superior performance than both the heuristic regularization parameter choice method and L-curve method based on the computational speed and localization error. PMID- 22047359 TI - Theoretical analysis of the thread effect in helical TomoTherapy. AB - PURPOSE: The longitudinal dose ripple on the off-axis caused by helical radiation delivery, such as the TomoTherapy system, has been observed, and its relation with respect to pitch has been studied with empirically found optimal pitches, 0.86/n, by Kissick et al. [Med. Phys. 32, 1414-1423 (2005)]. This ripple artifact referred to as the thread effect is periodic in nature and is caused by various periodic factors. In this work, the factors that cause the thread effect were unveiled, including jaw profile divergence, the inverse square law, attenuation, and the cone effect, and their impact on the thread effect were studied. METHODS: Mathematical formulation for individual and combined factors were set up. Based on theoretical analysis and simulations, optimal pitches that result in local minima of the ripple amplitude with respect to the jaw width and off-axis distance were identified and verified. The effectiveness of optimization in reducing the thread effect were also studied. RESULTS: Analysis and simulation based on the square-shaped jaw profiles well characterize the thread effect. Simulations based on the real jaw profiles show reduced ripples and very good agreement of optimal pitches compared with those based on the square profiles. The optimal pitches were found to have little jaw width dependence, except for the real jaw profile of small width (1.05 cm). The optimal pitches for the real jaw profile of width 1.05 cm are unidentifiable except for the largest ones, due to the relative smoothness of the jaw profile. With optimized intensity modulation, the thread effect can be largely suppressed. For real jaw profiles, the optimal pitches with or without dose optimization do not change much. The numbers 0.86/n found by Kissick et al. well approximate the optimal pitches for off-axis distance of 5 cm. However, optimal pitches are not universal for different off-axis distances: they decrease as the off-axis distance increases. CONCLUSIONS: The thread effect can be well explained by the proposed model. Optimization can largely reduce the thread effect. However, an optimal pitch reduces the ripple much easier especially when optimization is limited by many constraints. The optimal pitches predicted by the proposed model could be used as a reference for pitch selection regardless the tumor is at large or small off axis distance. PMID- 22047360 TI - Comparison of breast density measured on MR images acquired using fat-suppressed versus nonfat-suppressed sequences. AB - PURPOSE: To investigate the difference of MR percent breast density measured from fat-suppressed versus nonfat-suppressed imaging sequences. METHODS: Breast magnetic resonance imaging (MRI) with and without fat suppression was acquired from 38 subjects. Breasts were divided into subgroups of different morphological patterns ("central" and "intermingled" types). Breast volume, fibroglandular tissue volume, and percent density were measured. The results were compared using nonparametric statistical tests and regarded as significant at p < 0.05. RESULTS: Breast volume, fibroglandular volume, and percent density between fat-suppressed and nonfat-suppressed sequences were highly correlated. Breast volumes measured on these two sequences were almost identical. Fibroglandular tissue volume and percent density, however, had small (<5%) yet significant differences between the two sequences-they were both higher on the fat-suppressed sequence. Intraobserver variability was within 4% for both sequences and different morphological types. The fibroglandular tissue volume measured on downsampled images showed a small (<5%) yet significant difference. CONCLUSIONS: The measurement of breast density made on MRI acquired using fat-suppressed and nonfat-suppressed T1W images was about 5% difference, only slightly higher than the intraobserver variability of 3%-4%. When the density data from multiple centers were to be combined, evaluating the degree of difference is needed to take this difference into account. PMID- 22047361 TI - Image quality improvement in megavoltage cone beam CT using an imaging beam line and a sintered pixelated array system. AB - PURPOSE: To quantify the improvement in megavoltage cone beam computed tomography (MVCBCT) image quality enabled by the combination of a 4.2 MV imaging beam line (IBL) with a carbon electron target and a detector system equipped with a novel sintered pixelated array (SPA) of translucent Gd(2)O(2)S ceramic scintillator. Clinical MVCBCT images are traditionally acquired with the same 6 MV treatment beam line (TBL) that is used for cancer treatment, a standard amorphous Si (a-Si) flat panel imager, and the Kodak Lanex Fast-B (LFB) scintillator. The IBL produces a greater fluence of keV-range photons than the TBL, to which the detector response is more optimal, and the SPA is a more efficient scintillator than the LFB. METHODS: A prototype IBL + SPA system was installed on a Siemens Oncor linear accelerator equipped with the MVision(TM) image guided radiation therapy (IGRT) system. A SPA strip consisting of four neighboring tiles and measuring 40 cm by 10.96 cm in the crossplane and inplane directions, respectively, was installed in the flat panel imager. Head- and pelvis-sized phantom images were acquired at doses ranging from 3 to 60 cGy with three MVCBCT configurations: TBL + LFB, IBL + LFB, and IBL + SPA. Phantom image quality at each dose was quantified using the contrast-to-noise ratio (CNR) and modulation transfer function (MTF) metrics. Head and neck, thoracic, and pelvic (prostate) cancer patients were imaged with the three imaging system configurations at multiple doses ranging from 3 to 15 cGy. The systems were assessed qualitatively from the patient image data. RESULTS: For head and neck and pelvis-sized phantom images, imaging doses of 3 cGy or greater, and relative electron densities of 1.09 and 1.48, the CNR average improvement factors for imaging system change of TBL + LFB to IBL + LFB, IBL + LFB to IBL + SPA, and TBL + LFB to IBL + SPA were 1.63 (p < 10(- 8)), 1.64 (p < 10(- 13)), 2.66 (p < 10(- 9)), respectively. For all imaging doses, soft tissue contrast was more easily differentiated on IBL + SPA head and neck and pelvic images than TBL + LFB and IBL + LFB. IBL + SPA thoracic images were comparable to IBL + LFB images, but less noisy than TBL + LFB images at all imaging doses considered. The mean MTFs over all imaging doses were comparable, at within 3%, for all imaging system configurations for both the head- and pelvis-sized phantoms. CONCLUSIONS: Since CNR scales with the square root of imaging dose, changing from TBL + LFB to IBL + LFB and IBL + LFB to IBL + SPA reduces the imaging dose required to obtain a given CNR by factors of 0.38 and 0.37, respectively. MTFs were comparable between imaging system configurations. IBL + SPA patient image quality was always better than that of the TBL + LFB system and as good as or better than that of the IBL + LFB system, for a given dose. PMID- 22047362 TI - Learning statistical correlation for fast prostate registration in image-guided radiotherapy. AB - PURPOSE: In adaptive radiation therapy of prostate cancer, fast and accurate registration between the planning image and treatment images of the patient is of essential importance. With the authors' recently developed deformable surface model, prostate boundaries in each treatment image can be rapidly segmented and their correspondences (or relative deformations) to the prostate boundaries in the planning image are also established automatically. However, the dense correspondences on the nonboundary regions, which are important especially for transforming the treatment plan designed in the planning image space to each treatment image space, are remained unresolved. This paper presents a novel approach to learn the statistical correlation between deformations of prostate boundary and nonboundary regions, for rapidly estimating deformations of the nonboundary regions when given the deformations of the prostate boundary at a new treatment image. METHODS: The main contributions of the proposed method lie in the following aspects. First, the statistical deformation correlation will be learned from both current patient and other training patients, and further updated adaptively during the radiotherapy. Specifically, in the initial treatment stage when the number of treatment images collected from the current patient is small, the statistical deformation correlation is mainly learned from other training patients. As more treatment images are collected from the current patient, the patient-specific information will play a more important role in learning patient-specific statistical deformation correlation to effectively reflect prostate deformation of the current patient during the treatment. Eventually, only the patient-specific statistical deformation correlation is used to estimate dense correspondences when a sufficient number of treatment images have been acquired from the current patient. Second, the statistical deformation correlation will be learned by using a multiple linear regression (MLR) model, i.e., ridge regression (RR) model, which has the best prediction accuracy than other MLR models such as canonical correlation analysis (CCA) and principal component regression (PCR). RESULTS: To demonstrate the performance of the proposed method, we first evaluate its registration accuracy by comparing the deformation field predicted by our method with the deformation field estimated by the thin plate spline (TPS) based correspondence interpolation method on 306 serial prostate CT images of 24 patients. The average predictive error on the voxels around 5 mm of prostate boundary is 0.38 mm for our method of RR-based correlation model. Also, the corresponding maximum error is 2.89 mm. We then compare the speed for deformation interpolation by different methods. When considering the larger region of interest (ROI) with the size of 512 * 512 * 61, our method takes 24.41 seconds to interpolate the dense deformation field while TPS method needs 6.7 minutes; when considering a small ROI (surrounding prostate) with size of 112 * 110 * 93, our method takes 1.80 seconds, while TPS method needs 25 seconds. CONCLUSIONS: Experimental results show that the proposed method can achieve much faster registration speed yet with comparable registration accuracy, compared to the TPS-based correspondence (or deformation) interpolation approach. PMID- 22047363 TI - The correlation of tissue motion within the lung: implications on fiducial based treatments. AB - In radiation therapy many motion management and alignment techniques rely on the accuracy of an internal fiducial acting as a surrogate for target motion within the lung. Although fiducials are routinely used as surrogates for tumor motion, the extent to which varying spatial locations in the lung move similarly to other locations has yet to be quantitatively analyzed. In an attempt to analyze the motion correlation throughout the lung, ten primary lung cancer patients underwent IRB-approved 4DCT scans in the supine position. Deformable registration produced motion vectors for each voxel between exhalation and inhalation. Modeling was performed for each vector and all surrounding vectors within the lung in order to determine the mean 3D Euclidean distance necessary for an implanted fiducial to correlate with surrounding tissue motion to within 3 mm (left lower: 1.7 cm, left upper: 2.1 cm, right lower 1.6 cm, and right upper 2.9 cm). No general implantation rule of where to position a fiducial with respect to the tumor was found as the motion is highly patient and lobe specific. Correlation maps are presented showcasing spatial anisotropy of the motion of tissue surrounding the tumor. PMID- 22047364 TI - Improving suspicious breast lesion characterization using semi-automatic lesion fractional volume washout kinetic analysis. AB - PURPOSE: Although breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) demonstrates high sensitivity for malignant tumor detection, a major limitation is the relative low specificity, resulting in many false-positive diagnoses of suspicious lesions (BI-RADS assessment of 4 or 5) in clinical practice and consequently producing a relatively low positive predictive value (PPV) for biopsies. The most enhanced areas in the malignant tumors show a typical washout (WO) kinetic feature for the postcontrast signal intensity time courses and also correlate with microvessel density. Benign proliferative breast diseases can also produce the WO curve, yielding an equivocal kinetic behavior for the benign lesions and rendering their diagnoses as suspicious lesions in clinical practice. Considering that tumor angiogenesis is essential to an aggressive cancer tumor growth, the authors hypothesize that the WO volume fraction, i.e., the total volume of the WO voxels that demonstrate the WO curve within the tumor, is relatively large for malignant tumors in comparison to that for benign lesions. In this study, the authors present a lesion fractional volume WO kinetic analysis for improving the characterization of suspicious breast lesions. METHODS: A method to automatically detect the boundary of a manually selected contrast-enhanced lesion was introduced and tested, utilizing the signal intensity difference between the contrast-enhanced lesion and its surrounding tissues. The kinetic features of the postcontrast signal intensity time courses were quantitatively analyzed voxel-by-voxel with emphasis on the examination of the WO behavior. The WO volume fraction relative to the whole lesion volume was introduced and tested as a biomarker for improving the characterization of suspicious breast lesions. The sample for this test consisted of 28 suspicious lesions with correlative histopathology reports available. The lesions included 10 malignant tumors and 18 benign lesions, yielding a 35.7% PPV of the biopsies. RESULTS: The semi-automatic method produced an objective volume of interest for each lesion with voxelwise-quantified kinetic features. With an optimal choice of kinetic analysis, the mean and standard deviation of the WO volume fraction were 59.1 +/- 13.1 (%) with the range from 41.0% to 80.7% for the malignant tumors and 31.4 +/- 20.5 (%) with the range between 3.3% and 71.6% for the benign lesions, respectively. The WO volume fraction was significantly larger (p < 0.0004) for the malignant tumors than for the benign lesions. While maintaining the same sensitivity for malignant tumors, using the WO volume fraction as an additional biomarker would characterize 14 out of the 18 benign lesions as benign, potentially resulting in an 100% improvement rate in the PPV of the biopsies (from 35.7% to 71.4%) and consequently a 77.8% reduction rate in potentially unnecessary biopsies (from 18 to 4). CONCLUSIONS: The significantly larger WO volume fraction for the malignant tumors was probably related to the increased vascularity associated with tumor angiogenesis. The results suggest that the WO volume fraction biomarker has potential to improve the computer-based assessment of breast MRI by greatly increasing the PPV of breast biopsies and potentially significantly reducing the number of unnecessary biopsies without compromising sensitivity. PMID- 22047365 TI - The effect of errors in segmented attenuation maps on PET quantification. AB - PURPOSE: Accurate attenuation correction is important for PET quantification. Often, a segmented attenuation map is used, especially in MRI-based attenuation correction. As deriving the attenuation map from MRI images is difficult, different errors can be present in the segmented attenuation map. The goal of this paper is to determine the effect of these errors on quantification. METHODS: The authors simulated the digital XCAT phantom using the GATE Monte Carlo simulation framework and a model of the Philips Gemini TF. A whole body scan was simulated, spanning an axial field of view of 70 cm. A total of fifteen lesions were placed in the lung, liver, spine, colon, prostate, and femur. The acquired data were reconstructed with a reference attenuation map and with different attenuation maps that were modified to reflect common segmentation errors. The quantitative difference between reconstructed images was evaluated. RESULTS: Segmentation into five tissue classes, namely cortical bone, spongeous bone, soft tissue, lung, and air yielded errors below 5%. Large errors were caused by ignoring lung tissue (up to 45%) or cortical bone (up to 17%). The interpatient variability of lung attenuation coefficients can lead to errors of 10% and more. Up to 20% tissue misclassification from bone to soft tissue yielded errors below 5%. The same applies for up to 10% misclassification from lung to air. CONCLUSIONS: When using a segmented attenuation map, at least five different tissue types should be considered: cortical bone, spongeous bone, soft tissue, lung, and air. Furthermore, the interpatient variability of lung attenuation coefficients should be taken into account. Limited misclassification from bone to soft tissue and from lung to air is acceptable, as these do not lead to relevant errors. PMID- 22047366 TI - Reference dosimetry for helical tomotherapy: practical implementation and a multicenter validation. AB - PURPOSE: The aim of this study was to implement a protocol for reference dosimetry in tomotherapy and to validate the beam output measurements with an independent dosimetry system. METHODS: Beam output was measured at the reference depth of 10 cm in water for the following three cases: (1) a 5 * 10 cm(2) static machine specific reference field (MSR), (2) a rotational 5 * 10 cm(2) field without modulation and no tabletop in the beam, (3) a plan class specific reference (PCSR) field defined as a rotational homogeneous dose delivery to a cylindrical shaped target volume: plan with modulation and table-top movement. The formalism for reference dosimetry of small and nonstandard fields [Med.Phys.35: 5179-5186, 2008] and QA recommendations [Med.Phys.37: 4817-4853, 2010] were adopted in the dose measurement protocol. All ionization chamber measurements were verified independently using alanine/EPR dosimetry. As a pilot study, the beam output was measured on tomotherapy Hi-art systems at three other centers and directly compared to the centers specifications and to alanine dosimetry. RESULTS: For the four centers, the mean static output at a depth of 10 cm in water and SAD = 85 cm, measured with an A1SL chamber following the TG-148 report was 6.238 Gy/min +/- 0.058 (1 SD); the rotational output was 6.255 Gy/min +/- 0.069 (1 SD). The dose stated by the center was found in good agreement with the measurements of the visiting team: D(center)/D(visit) = 1.000 +/- 0.003 (1 SD). The A1SL chamber measurements were all in good agreement with Alanine/EPR dosimetry. Going from the static reference field to the rotational / non modulated field the dose rate remains constant within 0.2% except for one center where a deviation of 1.3% was detected. CONCLUSIONS: Following the TG-148 report, beam output measurements in water at the reference depth using a local protocol, as developed at different centers, was verified. The measurements were found in good agreement with alanine/EPR dosimetry. The presented methodology may provide a good concept for reference dosimetry. PMID- 22047367 TI - Scatter correction for full-fan volumetric CT using a stationary beam blocker in a single full scan. AB - PURPOSE: Applications of volumetric CT (VCT) are hampered by shading and streaking artifacts in the reconstructed images. These artifacts are mainly due to strong x-ray scatter signals accompanied with the large illumination area within one projection, which lead to CT number inaccuracy, image contrast loss and spatial nonuniformity. Although different scatter correction algorithms have been proposed in literature, a standard solution still remains unclear. Measurement-based methods use a beam blocker to acquire scatter samples. These techniques have unrivaled advantages over other existing algorithms in that they are simple and efficient, and achieve high scatter estimation accuracy without prior knowledge of the imaged object. Nevertheless, primary signal loss is inevitable in the scatter measurement, and multiple scans or moving the beam blocker during data acquisition are typically employed to compensate for the missing primary data. In this paper, we propose a new measurement-based scatter correction algorithm without primary compensation for full-fan VCT. An accurate reconstruction is obtained with one single-scan and a stationary x-ray beam blocker, two seemingly incompatible features which enable simple and efficient scatter correction without increase of scan time or patient dose. METHODS: Based on the CT reconstruction theory, we distribute the blocked data over the projection area where primary signals are considered approximately redundant in a full scan, such that the CT image quality is not degraded even with primary loss. Scatter is then accurately estimated by interpolation and scatter-corrected CT images are obtained using an FDK-based reconstruction algorithm. RESULTS: The proposed method is evaluated using two phantom studies on a tabletop CBCT system. On the Catphan(c)600 phantom, our approach reduces the reconstruction error from 207 Hounsfield unit (HU) to 9 HU in the selected region of interest, and improves the image contrast by a factor of 2.0 in the high-contrast regions. On an anthropomorphic head phantom, the reconstruction error is reduced from 97 HU to 6 HU in the soft tissue region and image spatial nonuniformity decreases from 27% to 5% after correction. CONCLUSIONS: Our method inherits the main advantages of measurement-based methods while avoiding their shortcomings. It has the potential to become a practical scatter correction solution widely implementable on different VCT systems. PMID- 22047368 TI - Dynamic MLC leaf sequencing for integrated linear accelerator control systems. AB - PURPOSE: Leaf positions for dynamic multileaf collimator (DMLC) intensity modulated radiation therapy must be closely synchronized with MU delivery. For the Varian C3 series MLC controller, if the planned trajectory (leaf position vs. MU) requires velocities exceeding the capability of the MLC, the leaves fall behind the planned positions, causing the controller to momentarily hold the beam and thereby introduce dosimetric errors. We investigated the merits of a new commercial linear accelerator, TrueBeamTM, that integrates MLC control with prospective dose rate modulation. If treatment is delivered at dose rates so high that leaves would fall behind, the controller reduces the dose rate such that harmony between MU and leaf position is preserved. METHODS: For three sets of DMLC leaf trajectories, point doses and two-dimensional dose distributions were measured in phantom using an ionization chamber and film, respectively. The first set, delivered using both a TrueBeamTM and a conventional C3 controller, comprised a single leaf bank closing at planned velocities of 2.4, 7.1, and 14 cm/s. The maximum achievable leaf velocity for both systems was 3 cm/s. The remaining two sets were derived from clinical fluence maps using a commercial treatment planning system for a range of planned dose rates and were delivered using TrueBeamTM set to the maximum dose rate, 600 MU/min. Generating trajectories using a planned dose rate that is lower than the delivery dose rate effectively increased the leaf velocity constraint used by the planning system for trajectory calculation. The second set of leaf trajectories was derived from two fluence maps containing regions of zero fluence obtained from representative beams of two different patient treatment plans. The third set was obtained from all nine fields of a head and neck treatment plan. For the head and neck plan, dose-volume histograms of the spinal cord and target for each planned dose rate were obtained. RESULTS: For the single closing leaf bank trajectories, the TrueBeamTM control system reduced the dose rate such that the leaf velocity was less than the maximum. Dose deviations relative to the 2.4 cm/s trajectory were less than 3%. For the conventional controller, the leaves repeatedly fell behind the planned positions until the beam hold threshold was reached, resulting in deviations of up to 19% relative to the 2.4 cm/s trajectory. For the two clinical fluence maps, reducing the planned dose rate reduced the dose in the zero fluence regions by 15% and 24% and increased the delivery time by 5 s and 14 s. No significant differences were noted in the high and intermediate dose regions measured using film. The DVHs for the head and neck plan showed a 10% reduction in cord dose for 20 MU/min relative to 600 MU/min sequencing dose rate, which was confirmed by measurement. No difference in target DVHs were observed. The reduction in cord dose increased total treatment time by 1.8 min. CONCLUSIONS: Leaf sequencing algorithms for integrated control systems should be modified to reflect the reduced importance of maximum leaf velocity for accurate dose delivery. PMID- 22047369 TI - A comparison of postimplant dosimetry for (103)Pd versus (131)Cs seeds on a retrospective series of PBSI patients. AB - PURPOSE: Permanent breast seed implantation (PBSI) is an accelerated partial breast irradiation technique performed using stranded (103)Pd radioactive seeds (average energy of 21 keV, 16.97 day half-life). Since 2004, (131)Cs brachytherapy sources have become clinically available. The (131)Cs radionuclide has a higher energy (average energy of 30 keV) and a shorter half-life (9.7 days) than (103)Pd. The purpose of this study was to determine whether or not there are dosimetric benefits to using (131)Cs brachytherapy seeds for PBSI. METHODS: The prescribed dose for PBSI using (103)Pd is 90 Gy, which was adjusted for (131)Cs implants to account for the shorter half-life. A retrospective cohort of 30 patients, who have already undergone a (103)Pd implant, was used for this study. The treatments were planned using the Variseed treatment planning system. The air kerma strength of the (131)Cs seeds was adjusted in all preimplantation treatment plans so that the V(100) (the volume within the target that receives 100% or more of the prescribed dose) were equivalent at time of implantation. Two month follow up CT scans were available for all 30 patients and each patient was reevaluated using (131)Cs seeds. The postimplant dosimetric parameters were compared using a two tailed t-test. RESULTS: The prescribed dose for (131)Cs was calculated to be 77 Gy; this dose would have the same biological effect as a PBSI implant with (103)Pd of 90 Gy. The activities of the (131)Cs sources were adjusted to an average of 2.2 +/- 0.8 U for (131)Cs compared to 2.5 +/- 1.1 U for (103)Pd in order to get an equivalent V(100) as the (103)Pd preimplants. While the use of (131)Cs significantly reduces the preimplant V(200) (the volume within the target that receives 200% or more of the prescribed dose) compared to (103)Pd by 13.5 +/ 9.0%, the reduction observed on the 2 month postimplant plan was 12.4 +/- 5.1% which accounted for seed motion, implantation inaccuracies and tissue changes. This translates into an absolute reduction of 4.1 cm(3) of tissue receiving 200% of the dose. CONCLUSIONS: This analysis of 30 early stage breast cancer patients who underwent the PBSI procedure shows that there is a theoretical dosimetric advantage to using (131)Cs. However, in a realistic implant that will have seed misplacements and tissue changes, the use of (131)Cs may not result in any clinically significant benefit. PMID- 22047370 TI - Statistical variability and confidence intervals for planar dose QA pass rates. AB - PURPOSE: The most common metric for comparing measured to calculated dose, such as for pretreatment quality assurance of intensity-modulated photon fields, is a pass rate (%) generated using percent difference (%Diff), distance-to-agreement (DTA), or some combination of the two (e.g., gamma evaluation). For many dosimeters, the grid of analyzed points corresponds to an array with a low areal density of point detectors. In these cases, the pass rates for any given comparison criteria are not absolute but exhibit statistical variability that is a function, in part, on the detector sampling geometry. In this work, the authors analyze the statistics of various methods commonly used to calculate pass rates and propose methods for establishing confidence intervals for pass rates obtained with low-density arrays. METHODS: Dose planes were acquired for 25 prostate and 79 head and neck intensity-modulated fields via diode array and electronic portal imaging device (EPID), and matching calculated dose planes were created via a commercial treatment planning system. Pass rates for each dose plane pair (both centered to the beam central axis) were calculated with several common comparison methods: %Diff/DTA composite analysis and gamma evaluation, using absolute dose comparison with both local and global normalization. Specialized software was designed to selectively sample the measured EPID response (very high data density) down to discrete points to simulate low-density measurements. The software was used to realign the simulated detector grid at many simulated positions with respect to the beam central axis, thereby altering the low-density sampled grid. Simulations were repeated with 100 positional iterations using a 1 detector/cm(2) uniform grid, a 2 detector/cm(2) uniform grid, and similar random detector grids. For each simulation, %/DTA composite pass rates were calculated with various %Diff/DTA criteria and for both local and global %Diff normalization techniques. RESULTS: For the prostate and head/neck cases studied, the pass rates obtained with gamma analysis of high density dose planes were 2%-5% higher than respective %/DTA composite analysis on average (ranging as high as 11%), depending on tolerances and normalization. Meanwhile, the pass rates obtained via local normalization were 2%-12% lower than with global maximum normalization on average (ranging as high as 27%), depending on tolerances and calculation method. Repositioning of simulated low-density sampled grids leads to a distribution of possible pass rates for each measured/calculated dose plane pair. These distributions can be predicted using a binomial distribution in order to establish confidence intervals that depend largely on the sampling density and the observed pass rate (i.e., the degree of difference between measured and calculated dose). These results can be extended to apply to 3D arrays of detectors, as well. CONCLUSIONS: Dose plane QA analysis can be greatly affected by choice of calculation metric and user-defined parameters, and so all pass rates should be reported with a complete description of calculation method. Pass rates for low-density arrays are subject to statistical uncertainty (vs. the high density pass rate), but these sampling errors can be modeled using statistical confidence intervals derived from the sampled pass rate and detector density. Thus, pass rates for low-density array measurements should be accompanied by a confidence interval indicating the uncertainty of each pass rate. PMID- 22047371 TI - Task-based weights for photon counting spectral x-ray imaging. AB - PURPOSE: To develop a framework for taking the spatial frequency composition of an imaging task into account when determining optimal bin weight factors for photon counting energy sensitive x-ray systems. A second purpose of the investigation is to evaluate the possible improvement compared to using pixel based weights. METHODS: The Fourier based approach of imaging performance and detectability index d' is applied to pulse height discriminating photon counting systems. The dependency of d' on the bin weight factors is made explicit, taking into account both differences in signal and noise transfer characteristics across bins and the spatial frequency dependency of interbin correlations from reabsorbed scatter. Using a simplified model of a specific silicon detector, d' values for a high and a low frequency imaging task are determined for optimal weights and compared to pixel based weights. RESULTS: The method successfully identifies bins where a large point spread function degrades detection of high spatial frequency targets. The method is also successful in determining how to downweigh highly correlated bins. Quantitative predictions for the simplified silicon detector model indicate that improvements in the detectability index when applying task-based weights instead of pixel based weights are small for high frequency targets, but could be in excess of 10% for low frequency tasks where scatter-induced correlation otherwise degrade detectability. CONCLUSIONS: The proposed method makes the spatial frequency dependency of complex correlation structures between bins and their effect on the system detective quantum efficiency easier to analyze and allows optimizing bin weights for given imaging tasks. A potential increase in detectability of double digit percents in silicon detector systems operated at typical CT energies (100 kVp) merits further evaluation on a real system. The method is noted to be of higher relevance for silicon detectors than for cadmium (zink) telluride detectors. PMID- 22047372 TI - Radiochromic film dosimetry of HDR (192)Ir source radiation fields. AB - PURPOSE: A radiochromic film based dosimetry system for high dose rate (HDR) Iridium-192 brachytherapy source was described. A comparison between calibration curves established in water and Solid WaterTM was provided. METHODS: Pieces of EBT-2 model GAFCHROMICTM film were irradiated in both water and Solid WaterTM with HDR (192)Ir brachytherapy source in a dose range from 0 to 50 Gy. Responses of EBT-2 GAFCHROMICTM film were compared for irradiations in water and Solid WaterTM by scaling the dose between media through Monte Carlo calculated conversion factor for both setups. To decrease uncertainty in dose delivery due to positioning of the film piece with respect to the radiation source, traceable calibration irradiations were performed in a parallel-opposed beam setup. RESULTS: The EBT-2 GAFCHROMICTM film based dosimetry system described in this work can provide an overall one-sigma dose uncertainty of 4.12% for doses above 1 Gy. The ratio of dose delivered to the sensitive layer of the film in water to the dose delivered to the sensitive layer of the film in Solid WaterTM was calculated using Monte Carlo simulations to be 0.9941 +/- 0.0007. CONCLUSIONS: A radiochromic film based dosimetry system using only the green color channel of a flatbed document scanner showed superior precision if used alone in a dose range that extends up to 50 Gy, which greatly decreases the complexity of work. In addition, Solid WaterTM material was shown to be a viable alternative to water in performing radiochromic film based dosimetry with HDR (192)Ir brachytherapy sources. PMID- 22047373 TI - Radiation dose reduction to the breast in thoracic CT: comparison of bismuth shielding, organ-based tube current modulation, and use of a globally decreased tube current. AB - PURPOSE: The purpose of this work was to evaluate dose performance and image quality in thoracic CT using three techniques to reduce dose to the breast: bismuth shielding, organ-based tube current modulation (TCM) and global tube current reduction. METHODS: Semi-anthropomorphic thorax phantoms of four different sizes (15, 30, 35, and 40 cm lateral width) were used for dose measurement and image quality assessment. Four scans were performed on each phantom using 100 or 120 kV with a clinical CT scanner: (1) reference scan; (2) scan with bismuth breast shield of an appropriate thickness; (3) scan with organ based TCM; and (4) scan with a global reduction in tube current chosen to match the dose reduction from bismuth shielding. Dose to the breast was measured with an ion chamber on the surface of the phantom. Image quality was evaluated by measuring the mean and standard deviation of CT numbers within the lung and heart regions. RESULTS: Compared to the reference scan, dose to the breast region was decreased by about 21% for the 15-cm phantom with a pediatric (2-ply) shield and by about 37% for the 30, 35, and 40-cm phantoms with adult (4-ply) shields. Organ based TCM decreased the dose by 12% for the 15-cm phantom, and 34-39% for the 30, 35, and 40-cm phantoms. Global lowering of the tube current reduced breast dose by 23% for the 15-cm phantom and 39% for the 30, 35, and 40-cm phantoms. In phantoms of all four sizes, image noise was increased in both the lung and heart regions with bismuth shielding. No significant increase in noise was observed with organ-based TCM. Decreasing tube current globally led to similar noise increases as bismuth shielding. Streak and beam hardening artifacts, and a resulting artifactual increase in CT numbers, were observed for scans with bismuth shields, but not for organ-based TCM or global tube current reduction. CONCLUSIONS: Organ-based TCM produces dose reduction to the breast similar to that achieved with bismuth shielding for both pediatric and adult phantoms. However, organ-based TCM does not affect image noise or CT number accuracy, both of which are adversely affected by bismuth shielding. Alternatively, globally decreasing the tube current can produce the same dose reduction to the breast as bismuth shielding, with a similar noise increase, yet without the streak artifacts and CT number errors caused by the bismuth shields. Moreover, globally decreasing the tube current reduces the dose to all tissues scanned, not simply to the breast. PMID- 22047374 TI - Zonal segmentation of prostate using multispectral magnetic resonance images. AB - PURPOSE: To investigate the performance of a new method of automatic segmentation of prostatic multispectral magnetic resonance images into two zones: the peripheral zone and the central gland. METHODS: The proposed method is based on a modified version of the evidential C-means clustering algorithm. The evidential C means optimization process was modified to introduce spatial neighborhood information. A priori knowledge of the prostate's zonal morphology was modeled as a geometric criterion and used as an additional data source to enhance the differentiation of the two zones. RESULTS: Thirty-one clinical magnetic resonance imaging series were used to validate the method, and interobserver variability was taken into account in assessing its accuracy. The mean Dice Similarity Coefficient was 89% for the central gland and 80% for the peripheral zone, as validated by a consensus from expert radiologist segmentation. CONCLUSIONS: The method was statistically insensitive to variations in patient age, prostate volume and the presence of tumors, which increases its feasibility in a clinical context. PMID- 22047375 TI - Impact of leaf motion constraints on IMAT plan quality, deliver accuracy, and efficiency. AB - PURPOSE: Intensity modulated arc therapy (IMAT) is a radiation therapy delivery technique that combines the efficiency of arc based delivery with the dose painting capabilities of intensity modulated radiation therapy (IMRT). A key challenge in developing robust inverse planning solutions for IMAT is the need to account for the connectivity of the beam shapes as the gantry rotates from one beam angle to the next. To overcome this challenge, inverse planning solutions typically impose a leaf motion constraint that defines the maximum distance a multileaf collimator (MLC) leaf can travel between adjacent control points. The leaf motion constraint ensures the deliverability of the optimized plan, but it also impacts the plan quality, the delivery accuracy, and the delivery efficiency. In this work, the authors have studied leaf motion constraints in detail and have developed recommendations for optimizing the balance between plan quality and delivery efficiency. METHODS: Two steps were used to generate optimized IMAT treatment plans. The first was the direct machine parameter optimization (DMPO) inverse planning module in the Pinnacle(3) planning system. Then, a home-grown arc sequencer was applied to convert the optimized intensity maps into deliverable IMAT arcs. IMAT leaf motion constraints were imposed using limits of between 1 and 30 mm/deg. Dose distributions were calculated using the convolution/superposition algorithm in the Pinnacle(3) planning system. The IMAT plan dose calculation accuracy was examined using a finer sampling calculation and the quality assurance verification. All plans were delivered on an Elekta Synergy with an 80-leaf MLC and were verified using an IBA MatriXX 2D ion chamber array inserted in a MultiCube solid water phantom. RESULTS: The use of a more restrictive leaf motion constraint (less than 1-2 mm/deg) results in inferior plan quality. A less restrictive leaf motion constraint (greater than 5 mm/deg) results in improved plan quality but can lead to less accurate dose distribution as evidenced by increasing discrepancies between the planned and the delivered doses. For example, the results from our patient-specific quality assurance measurements demonstrated that the average gamma analysis passing rate decreased from 98% to 80% when the allowable leaf motion increased from 3 to 20 mm/deg. Larger leaf motion constraints also led to longer treatment delivery times (2 to 4 folds) due to the additional MLC leaf motion. CONCLUSIONS: Leaf motion constraints significantly impact IMAT plans in terms of plan quality, delivery accuracy, and delivery efficiency with the impact magnified for more complex cases. Our studies indicate that a leaf motion constraint of 2 to 3 mm/deg of gantry rotation can provide an optimal balance between plan quality, delivery accuracy, and efficiency. PMID- 22047376 TI - Analysis of shear strain imaging for classifying breast masses: finite element and phantom results. AB - PURPOSE: Features extracted from axial-shear strain images of breast masses have been previously utilized to differentiate and classify benign from malignant breast masses. In this paper, we compare shear strain patterns exhibited by both the full-shear (axial and lateral component) versus only the axial-shear strain component for differentiating between bound masses (malignant) when compared to unbound masses (benign). METHODS: We examine different breast mass characteristics such as mass shape, asymmetric location of masses, stiffness variations, and mass bonding characteristics to background tissue to assess their impact on shear strain patterns generated due to a uniaxial applied deformation. Two-dimensional finite element simulations of both circular and elliptical inclusions embedded within a uniform background were utilized. Different degrees of bonding were characterized using friction coefficient values ranging from 0.01 to 100 denoting loosely bound to firmly bound masses. Single-inclusion tissue mimicking phantoms mimicking firmly bound and loosely bound ellipsoidal masses oriented at four different angles to the applied deformation were studied to corroborate the mass differentiation performance. RESULTS: Our results indicate that the normalized axial-shear strain and full-shear strain area features are larger for bound when compared to unbound masses. A higher stiffness ratio or contrast between the inclusion and background also improves differentiation. Larger applied deformations reduce the discrimination performance for masses with friction coefficients lower than 0.4, due to increased mass slippage with applied deformations. Potential errors with the use of these features would occur for unbound inclusions at larger applied deformations and for asymmetric mass positions within the background normal tissue. CONCLUSIONS: Finite element and tissue-mimicking phantom results demonstrate the feasibility of utilizing both the normalized axial-shear and full-shear strain area features to classify breast masses. Differentiation between bound or unbound masses was not affected by the mass size or shape for masses where the applied deformation is normal to the mass surface. Shear strain patterns vary significantly especially within unbound masses, when the mass surface is not normal to the applied deformation. Discrimination performance for unbound masses was improved by utilizing only the normalized shear strain area patterns located outside the mass as illustrated in this paper. PMID- 22047377 TI - Automated bone removal in CT angiography: comparison of methods based on single energy and dual energy scans. AB - PURPOSE: To evaluate dual energy based methods for bone removal in computed tomography angiography (CTA) images and compare these with single energy based methods that use an additional, nonenhanced, CT scan. METHODS: Four different bone removal methods were applied to CT scans of an anthropomorphic thorax phantom, acquired with a second generation dual source CT scanner. The methods differed by the way information on the presence of bone was obtained (either by using an additional, nonenhanced scan or by scanning with two tube voltages at the same time) and by the way the bone was removed from the CTA images (either by masking or subtracting the bone). The phantom contained parts which mimic vessels of various diameters in direct contact with bone. Both a quantitative and qualitative analysis of image quality after bone removal was performed. Image quality was quantified by the contrast-to-noise ratio (CNR) normalized to the square root of the dose (CNRD). At locations where vessels touch bone, the quality of the bone removal and the vessel preservation were visually assessed. The dual energy based methods were assessed with and without the addition of a 0.4 mm tin filter to the high voltage x-ray tube filtration. For each bone removal method, the dose required to obtain a certain CNR after bone removal was compared with the dose of a reference scan with the same CNR but without automated bone removal. The CNRD value of the reference scan was maximized by choosing the lowest tube voltage available. RESULTS: All methods removed the bone completely. CNRD values were higher for the masking based methods than for the subtraction based methods. Single energy based methods had a higher CNRD value than the corresponding dual energy based methods. For the subtraction based dual energy method, tin filtration improved the CNRD value with approximately 50%. For the masking based dual energy method, it was easier to differentiate between iodine and bone when tin filtration was applied. The CNRD value decreased only with 4% in that case. Compared to the dual scan based methods, the dual energy based methods had the advantage that only a single scan was made without the need of image registration. This might be easier to implement in clinical practice. Vessel preservation was better with bone subtraction than with bone masking. Smaller vessels were completely occluded by the bone mask. None of the bone removal methods was dose neutral. CONCLUSIONS: In general, dual scan based methods that use the lowest tube voltage available, have a higher CNR than the dual energy based approaches at the same dose level. Tin filtration improves the ability to differentiate between iodine and bone for the dual energy based masking method. In clinical practice, the advantages of the dual energy masking method might outweigh its disadvantage of a slightly higher dose penalty compared to the conventional dual scan masking method. PMID- 22047378 TI - K-space reconstruction with anisotropic kernel support (KARAOKE) for ultrafast partially parallel imaging. AB - PURPOSE: Partially parallel imaging (PPI) greatly accelerates MR imaging by using surface coil arrays and under-sampling k-space. However, the reduction factor (R) in PPI is theoretically constrained by the number of coils (N(C)). A symmetrically shaped kernel is typically used, but this often prevents even the theoretically possible R from being achieved. Here, the authors propose a kernel design method to accelerate PPI faster than R = N(C). METHODS: K-space data demonstrates an anisotropic pattern that is correlated with the object itself and to the asymmetry of the coil sensitivity profile, which is caused by coil placement and B(1) inhomogeneity. From spatial analysis theory, reconstruction of such pattern is best achieved by a signal-dependent anisotropic shape kernel. As a result, the authors propose the use of asymmetric kernels to improve k-space reconstruction. The authors fit a bivariate Gaussian function to the local signal magnitude of each coil, then threshold this function to extract the kernel elements. A perceptual difference model (Case-PDM) was employed to quantitatively evaluate image quality. RESULTS: A MR phantom experiment showed that k-space anisotropy increased as a function of magnetic field strength. The authors tested a K-spAce Reconstruction with AnisOtropic KErnel support ("KARAOKE") algorithm with both MR phantom and in vivo data sets, and compared the reconstructions to those produced by GRAPPA, a popular PPI reconstruction method. By exploiting k space anisotropy, KARAOKE was able to better preserve edges, which is particularly useful for cardiac imaging and motion correction, while GRAPPA failed at a high R near or exceeding N(C). KARAOKE performed comparably to GRAPPA at low Rs. CONCLUSIONS: As a rule of thumb, KARAOKE reconstruction should always be used for higher quality k-space reconstruction, particularly when PPI data is acquired at high Rs and/or high field strength. PMID- 22047379 TI - Dosimetry of a new P-32 ophthalmic applicator. AB - PURPOSE: The potential of P-32 ophthalmic applicator irradiation after pterygium excision has been demonstrated as an alternative to Sr/Y-90 irradiation. This study aimed to provide the clinical dosimetry for this new applicator. METHODS: The prototype of a cylindrical P-32 applicator was fabricated according to the Monte Carlo (MC)-based design study. At a nominal activity of 6 mCi (0.22 GBq), the absorbed dose rate at the front surface (i.e., reference dose rate) was measured by using an extrapolation ionization chamber (EC). The radiochromic film (RCF) was also used to measure the reference dose, axial depth dose distributions and transaxial dose profiles at various depths in water. RESULTS: The reference dose rate was 3.89 +/- 0.14 cGy/s for EC and 3.84 +/- 0.25 cGy/s for RCF. The depth dose rate was reduced approximately by an order of magnitude for every 2 mm depth in water. Measured depth doses in depths of 0.5-2.5 mm agreed with Monte Carlo data within +/-3%. Due to nonuniform absorption of P-32 into an absorbent disk, the dose profiles were not symmetric and decreased more rapidly toward the periphery than those predicted by the MC. The authors confirmed no leakage of P 32 activities and negligible exposure rate around the hand grip of the applicator. CONCLUSIONS: The P-32 applicator can deliver therapeutic doses to the surface of the conjunctiva, while sparing the lens better than Sr/Y-90 applicators. The doses at any points from the P-32 applicator could be calculated by using the measured dosimetry data. They also confirmed no leakage of the source, reliable integrity of the applicator, and negligible exposure level around the hand grip of the applicator. However, due to a possibility of nonuniform distributions of P-32 in an absorbent disk, measuring dose profiles as well as the reference dose rate for every new applicator would be recommended. PMID- 22047380 TI - Imaging of moving fiducial markers during radiotherapy using a fast, efficient active pixel sensor based EPID. AB - PURPOSE: The purpose of this work was to investigate the use of an experimental complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) for tracking of moving fiducial markers during radiotherapy. METHODS: The APS has an active area of 5.4 * 5.4 cm and maximum full frame read-out rate of 20 frame s( 1), with the option to read out a region-of-interest (ROI) at an increased rate. It was coupled to a 4 mm thick ZnWO4 scintillator which provided a quantum efficiency (QE) of 8% for a 6 MV x-ray treatment beam. The APS was compared with a standard iViewGT flat panel amorphous Silicon (a-Si) electronic portal imaging device (EPID), with a QE of 0.34% and a frame-rate of 2.5 frame s(-1). To investigate the ability of the two systems to image markers, four gold cylinders of length 8 mm and diameter 0.8, 1.2, 1.6, and 2 mm were placed on a motion platform. Images of the stationary markers were acquired using the APS at a frame rate of 20 frame s(-1), and a dose-rate of 143 MU min(-1) to avoid saturation. EPID images were acquired at the maximum frame-rate of 2.5 frame s(-1), and a reduced dose-rate of 19 MU min(-1) to provide a similar dose per frame to the APS. Signal-to-noise ratio (SNR) of the background signal and contrast-to-noise ratio (CNR) of the marker signal relative to the background were evaluated for both imagers at doses of 0.125 to 2 MU. RESULTS: Image quality and marker visibility was found to be greater in the APS with SNR ~5 times greater than in the EPID and CNR up to an order of magnitude greater for all four markers. To investigate the ability to image and track moving markers the motion-platform was moved to simulate a breathing cycle with period 6 s, amplitude 20 mm and maximum speed 13.2 mm s(-1). At the minimum integration time of 50 ms a tracking algorithm applied to the APS data found all four markers with a success rate of >=92% and positional error <=90 MUm. At an integration time of 400 ms the smallest marker became difficult to detect when moving. The detection of moving markers using the a-Si EPID was difficult even at the maximum dose-rate of 592 MU min(-1) due to the lower QE and longer integration time of 400 ms. CONCLUSIONS: This work demonstrates that a fast read-out, high QE APS may be useful in the tracking of moving fiducial markers during radiotherapy. Further study is required to investigate the tracking of markers moving in 3D in a treatment beam attenuated by moving patient anatomy. This will require a larger sensor with ROI read-out to maintain speed and a manageable data-rate. PMID- 22047381 TI - Auto-segmentation of normal and target structures in head and neck CT images: a feature-driven model-based approach. AB - PURPOSE: Intensity modulated radiation therapy (IMRT) allows greater control over dose distribution, which leads to a decrease in radiation related toxicity. IMRT, however, requires precise and accurate delineation of the organs at risk and target volumes. Manual delineation is tedious and suffers from both interobserver and intraobserver variability. State of the art auto-segmentation methods are either atlas-based, model-based or hybrid however, robust fully automated segmentation is often difficult due to the insufficient discriminative information provided by standard medical imaging modalities for certain tissue types. In this paper, the authors present a fully automated hybrid approach which combines deformable registration with the model-based approach to accurately segment normal and target tissues from head and neck CT images. METHODS: The segmentation process starts by using an average atlas to reliably identify salient landmarks in the patient image. The relationship between these landmarks and the reference dataset serves to guide a deformable registration algorithm, which allows for a close initialization of a set of organ-specific deformable models in the patient image, ensuring their robust adaptation to the boundaries of the structures. Finally, the models are automatically fine adjusted by our boundary refinement approach which attempts to model the uncertainty in model adaptation using a probabilistic mask. This uncertainty is subsequently resolved by voxel classification based on local low-level organ-specific features. RESULTS: To quantitatively evaluate the method, they auto-segment several organs at risk and target tissues from 10 head and neck CT images. They compare the segmentations to the manual delineations outlined by the expert. The evaluation is carried out by estimating two common quantitative measures on 10 datasets: volume overlap fraction or the Dice similarity coefficient (DSC), and a geometrical metric, the median symmetric Hausdorff distance (HD), which is evaluated slice-wise. They achieve an average overlap of 93% for the mandible, 91% for the brainstem, 83% for the parotids, 83% for the submandibular glands, and 74% for the lymph node levels. CONCLUSIONS: Our automated segmentation framework is able to segment anatomy in the head and neck region with high accuracy within a clinically-acceptable segmentation time. PMID- 22047382 TI - Radiochromic EBT2 film dosimetry for low-energy protontherapy. AB - PURPOSE: In protontherapy, accessories are used in order to adapt the beam to the surface and to the depth of the target. They are positioned close to the patient in order to avoid perturbation effects related to proton scattering. The level of contamination of the beam caused by these accessories may be assessed by examining the dose maps in parallel planes to the beam incidence. The EBT2 radiochromic film is a suitable tool for this task, as it can be cut into small pieces and immersed in water. Prior to use the EBT2 film for dose measurements, its response when exposed to a proton beam must be analysed. METHODS: The measurements were performed at the Centre Antoine Lacassagne, using the hospital based MEDICYC isochronous cyclotron which provides 65 MeV protons. Monoenergetic as well as polyenergetic beams were used. Small pieces of EBT2 films were irradiated with proton beams in a small water phantom. Films were exposed at various angles close to the beam incidence and received doses ranging from 0.25 to 500 Gy. The optical density (OD) was studied as a function of angle, dose and linear energy transfer (LET). RESULTS: The effective atomic number of the active layer of the film is close to that of water which prevents disturbances of the measurement. However, the high density and the significant thickness of the Mylar substrate surrounding the active layer affect the use of the film in a parallel orientation to the beam. Therefore, the substrate layer may totally or partially slow down the protons. The measurement is then no longer representative to what happens in water. The measurement errors can be corrected by applying a tilt angle of at least 5 degrees between the film and the beam. The dose analysis reveals that the green channel is the most sensitive in the dose range from 1 to 100 Gy. The OD is accurately described by a Weibull function of the dose with four free parameters. The Weibull function is valid for both monoenergetic and polyenergetic beams if the LET is limited to values below 15 MeV g(- 1) cm(2). When using a film orientation close to the beam incidence angle, increasing LET values are encountered throughout the film axis gradually with the protons slowing down in water. The EBT2 films show an underestimated response for higher LET values. The comparison of data from the present study to data obtained by other authors for EBT films allows modelling the underestimated response as a function of the LET. The definition improvement of the link between OD and LET requires to integrate more closely the beam energy characteristics. CONCLUSIONS: The EBT2 film is a suitable dosimeter for analysing dose plans in planes nearly parallel to the beam orientation by compensating the underestimated dose response due to LET. PMID- 22047383 TI - Automated 3-dimensional segmentation of pelvic lymph nodes in magnetic resonance images. AB - PURPOSE: Computer aided diagnosis (CAD) of lymph node metastases may help reduce reading time and improve interpretation of the large amount of image data in a 3 D pelvic MRI exam. The purpose of this study was to develop an algorithm for automated segmentation of pelvic lymph nodes from a single seed point, as part of a CAD system for the classification of normal vs metastatic lymph nodes, and to evaluate its performance compared to other algorithms. METHODS: The authors' database consisted of pelvic MR images of 146 consecutive patients, acquired between January 2008 and April 2010. Each dataset included four different MR sequences, acquired after infusion of a lymph node specific contrast medium based on ultrasmall superparamagnetic particles of iron oxide. All data sets were analyzed by two expert readers who, reading in consensus, annotated and manually segmented the lymph nodes. The authors compared four segmentation algorithms: confidence connected region growing (CCRG), extended CCRG (ECC), graph cut segmentation (GCS), and a segmentation method based on a parametric shape and appearance model (PSAM). The methods were ranked based on spatial overlap with the manual segmentations, and based on diagnostic accuracy in a CAD system, with the experts' annotations as reference standard. RESULTS: A total of 2347 manually annotated lymph nodes were included in the analysis, of which 566 contained a metastasis. The mean spatial overlap (Dice similarity coefficient) was: 0.35 (CCRG), 0.57 (ECC), 0.44 (GCS), and 0.46 (PSAM). When combined with the classification system, the area under the ROC curve was: 0.805 (CCRG), 0.890 (ECC), 0.807 (GCS), 0.891 (PSAM), and 0.935 (manual segmentation). CONCLUSIONS: We identified two segmentation methods, ECC and PSAM, that achieve a high diagnostic accuracy when used in conjunction with a CAD system for classification of normal vs metastatic lymph nodes. The manual segmentations still achieve the highest diagnostic accuracy. PMID- 22047384 TI - Optimization of phosphor-based detector design for oblique x-ray incidence in digital breast tomosynthesis. AB - PURPOSE: In digital breast tomosynthesis (DBT), a volumetric reconstruction of the breast is generated from a limited range of x-ray projections. One trade-off of DBT is resolution loss in the projections due to non-normal (i.e., oblique) x ray incidence. Although degradation in image quality due to oblique incidence has been studied using empirical data and Monte Carlo simulations, a theoretical treatment has been lacking. The purpose of this work is to extend Swank's calculations of the transfer functions of turbid granular phosphors to oblique incidence. The model is ultimately used as a tool for optimizing the design of DBT detectors. METHODS: A quantum-limited system and 20 keV x-rays are considered. Under these assumptions, the modulation transfer function (MTF) and noise power spectra (NPS) are derived using the diffusion approximation to the Boltzmann equation to model optical scatter within the phosphor. This approach is applicable to a nonstructured scintillator such as gadolinium oxysulfide doped with terbium (Gd(2)O(2)S:Tb), which is commonly used in breast imaging and which can reasonably approximate other detector materials. The detective quantum efficiency (DQE) is then determined from the Nishikawa formulation, where it is written as the product of the x-ray quantum detection efficiency, the Swank factor, and the Lubberts fraction. Transfer functions are calculated for both front- and back-screen configurations, which differ by positioning the photocathode at the exit or entrance point of the x-ray beam, respectively. RESULTS: In the front-screen configuration, MTF and DQE are found to have considerable angular dependence, while NPS is shown to vary minimally with projection angle. As expected, the high frequency MTF and DQE are degraded substantially at large angles. By contrast, all transfer functions for the back screen configuration have the advantage of significantly less angular dependence. Using these models, we investigated the possibility for optimizing the design of DBT detectors. As an example optimization strategy, the phosphor thickness which maximizes the DQE at a fixed frequency is analyzed. This work demonstrates that the optimal phosphor thickness for the front-screen is angularly dependent, shifting to lower thickness at higher angles. Conversely, the back-screen is not optimized by a single thickness but instead attains reasonably high DQE values over a large range of thicknesses. Although the back-screen configuration is not suited for current detectors using a glass substrate, it may prove to be preferred in future detectors using newly proposed plastic thin-film transistor (TFT) substrates. CONCLUSIONS: Using the diffusion approximation to the Boltzmann equation to model the spread of light in a scintillator, this paper develops an analytical model of MTF, NPS, and DQE for a phosphor irradiated obliquely. The model is set apart from other studies on oblique incidence in being derived from first principles. This work has applications in the optimization of DBT detector design. PMID- 22047385 TI - An approach for online evaluations of dose consequences caused by small rotational setup errors in intracranial stereotactic radiation therapy. AB - PURPOSE: The purpose of this work is to investigate the impact of small rotational errors on the magnitudes and distributions of spatial dose variations for intracranial stereotactic radiotherapy (SRT) treatment setups, and to assess the feasibility of using the original dose map overlaid with rotated contours (ODMORC) method as a fast, online evaluation tool to estimate dose changes (using DVHs) to clinical target volumes (CTVs) and organs-at-risks (OARs) caused by small rotational setup errors. METHODS: Fifteen intracranial SRT cases treated with either three-dimensional conformal radiation therapy (3DCRT) or intensity modulated radiation therapy (IMRT) techniques were chosen for the study. Selected cases have a variety of anatomical dimensions and pathologies. Angles of +/-3 degrees and +/-5 degrees in all directions were selected to simulate the rotational errors. Dose variations in different regions of the brain, CTVs, and OARs were evaluated to illustrate the various spatial effects of dose differences before and after rotations. DVHs accounting for rotations that were recomputed by the treatment planning system (TPS) and those generated by the ODMORC method were compared. A framework of a fast algorithm for multicontour rotation implemented by ODMORC is introduced as well. RESULTS: The average values of relative dose variations between original dose and recomputed dose accounting for rotations were greater than 4.0% and 10.0% in absolute mean and in standard deviation, respectively, at the skull and adjacent regions for all cases. They were less than 1.0% and 2.5% in absolute mean and in standard deviation, respectively, for dose points 3 mm away from the skull. The results indicated that spatial dose to any part of the brain organs or tumors separated from the skull or head surface would be relatively stable before and after rotations. Statistical data of CTVs and OARs indicate the lens and cochleas have the large dose variations before and after rotations, whereas the remaining ROIs have insignificant dose differences. DVH comparisons suggest that the ODMORC method is able to estimate the DVH of CTVs fairly accurately (within 1.5% of relative dose differences for evaluation volumes). The results also show that most of the OARs including the brain stem, spinal cord, chiasm, hippocampuses, optic nerves, and retinas, which were relatively distal from the skull and surface, had good agreement (within 2.0% of relative dose differences for 0.1 cc of the volumes ) between the ODMORC method and the recomputation, whereas OARs more proximate to the bone-tissue interface or surface, such as the lenses and cochlea, had larger dose variations (greater than 5.0%) for some cases due to the incapability of the ODMORC to account for scatter contribution variations proximate to interfaces and intrinsic dose calculation uncertainties for ROIs with small volumes. CONCLUSIONS: The ODMORC method can be implemented as an online evaluation system for rotation-induced dose changes of CTVs and most OARs and for other related dose consequence analyses. PMID- 22047386 TI - Assessment of three methods for detection of ultrasound artifacts. AB - PURPOSE: The purpose of this work is to measure the performance (sensitivity and specificity) of three different visually based methods of detecting ultrasound artifacts using dynamic clips obtained with a liquid phantom. It is important to detect the presence of these non uniformities as early as possible, so they can be assessed, tracked, and addressed well before clinical image quality is impacted. METHODS: A total of 28 transducers of varying models containing a single artificial artifact created by stretching thin filaments across the transducer face were prepared. A second set of 28 matching transducers contained no artifacts. A 10 s clip was recorded of a dynamic speckle pattern from a custom liquid phantom ("dynamic clip"). A single-frame image was obtained by computing the median values at each pixel location over all frames of the clip ("median image"). This single-frame median image was then subtracted from a baseline image previously obtained with no induced artifact ("subtracted median"). All images were evaluated by six observers. The mean sensitivity and specificity with 95% exact binomial confidence intervals for the three artifact detection methods were estimated. Evaluation time and observer confidence were recorded. RESULTS: Both single-frame median and subtracted median images had a higher sensitivity than the dynamic clip. Overall the subtracted median images had the highest sensitivity of 97%, while maintaining a high specificity of 92%. Observers identified artifacts in the shortest time and with the highest confidence with this method. The subtracted median method removed the original structural variations and non-uniformities, and reduced the likelihood of false-positives. CONCLUSIONS: From the three methods assessed in this study, subtracted median images allow detection of artifacts with very good sensitivity and specificity, low image evaluation times, and a high degree of observer confidence, making these ideal for routine QC. For acceptance testing, where there are no previous baseline images available for subtraction, the use of median images is useful, although comparison with median images from different transducers of the same model and / or comparison of impressions from multiple observers should be made to decrease the incidence of false-positive findings. If median and subtracted median images are not available, direct inspection of the dynamic B-mode clips is useful for acceptance testing and quality control, but with lower sensitivity and somewhat longer evaluation time. PMID- 22047387 TI - Megavoltage cone beam CT near surface dose measurements: potential implications for breast radiotherapy. AB - PURPOSE: Cone beam computed tomography (CBCT) is fast becoming standard on modern linear accelerators. CBCT increases the dose to regions within and outside the treatment field, potentially increasing secondary cancer induction and toxicity. This study quantified megavoltage (MV) CBCT skin dose and compared it to skin dose delivered during standard tangential breast radiotherapy. METHOD: Dosimetry was performed both in- and out-of-field using thermoluminescent dosimeters (TLDs) and a metal-oxide-semiconductor-field-effect-transistor (MOSFET) detector specifically designed for skin dosimetry; these were placed superficially on a female anthropomorphic phantom. RESULTS: The skin dose from a single treatment fraction ranged from 0.5 to 1.4 Gy on the ipsilateral breast, 0.031-0.18 Gy on the contralateral breast, and 0-0.02 Gy in the head and pelvic region. An 8 MU MV CBCT delivered a skin dose that ranged from 0.02 to 0.05 Gy in the chest region and was less than 0.01 Gy in the head and pelvis regions. One MV CBCT per fraction was found to increase the out-of-field skin dose from both the CBCT and the treatment fields by approximately 20%. The imaging dose as a percentage of treatment doses in the ipsilateral breast region was 3% for both dosimeters. CONCLUSION: Imaging increases the skin dose to regions outside the treatment field particularly regions immediately adjacent the target volume. This small extra dose to the breasts should be considered when developing clinical protocols and assessing dose for clinical trials. PMID- 22047388 TI - Accuracy of Acuros XB and AAA dose calculation for small fields with reference to RapidArc((r)) stereotactic treatments. AB - PURPOSE: To assess the accuracy against measurements of two photon dose calculation algorithms (Acuros XB and the Anisotropic Analytical algorithm AAA) for small fields usable in stereotactic treatments with particular focus on RapidArc((r)). METHODS: Acuros XB and AAA were configured for stereotactic use. Baseline accuracy was assessed on small jaw-collimated open fields for different values for the spot sizes parameter in the beam data: 0.0, 0.5, 1, and 2 mm. Data were calculated with a grid of 1 * 1 mm(2). Investigated fields were: 3 * 3, 2 * 2, 1 * 1, and 0.8 * 0.8 cm(2) with a 6 MV photon beam generated from a Clinac2100iX (Varian, Palo Alto, CA). Profiles, PDD, and output factors were measured in water with a PTW diamond detector (detector size: 4 mm(2), thickness 0.4 mm) and compared to calculations. Four RapidArc test plans were optimized, calculated and delivered with jaw settings J3 * 3, J2 * 2, and J1 * 1 cm(2), the last was optimized twice to generate high (H) and low (L) modulation patterns. Each plan consisted of one partial arc (gantry 110 degrees to 250 degrees ), and collimator 45 degrees . Dose to isocenter was measured in a PTW Octavius phantom and compared to calculations. 2D measurements were performed by means of portal dosimetry with the GLAaS method developed at authors' institute. Analysis was performed with gamma pass-fail test with 3% dose difference and 2 mm distance to agreement thresholds. RESULTS: Open square fields: penumbrae from open field profiles were in good agreement with diamond measurements for 1 mm spot size setting for Acuros XB, and between 0.5 and 1 mm for AAA. Maximum MU difference between calculations and measurements was 1.7% for Acuros XB (0.2% for fields greater than 1 * 1 cm(2)) with 0.5 or 1 mm spot size. Agreement for AAA was within 0.7% (2.8%) for 0.5 (1 mm) spot size. RapidArc plans: doses were evaluated in a 4 mm diameter structure at isocenter and computed values differed from measurements by 0.0, -0.2, 5.5, and -3.4% for Acuros XB calculations (1 mm spot size), and of -0.1, 0.3, 6.7, and -1.2% for AAA, respectively for J3 * 3, J2 * 2, J1 * 1H, J1 * 1L RapidArc plans. Gamma Agreement Index from 2D dose analysis was higher than 95% for J3 * 3 and J2 * 2 plans, being around 80% for J1 * 1 maps. Sensitivity with respect to the dosimetric leaf gap and transmission factor MLC parameters was evaluated in the four RapidArc plans, showing the need to properly set the dosimetric leaf gap for accurate calculations. CONCLUSIONS: Acuros XB and AAA showed acceptable characteristics for stereotactic small fields if adequate tuning of configuration parameters is performed. Dose calculated for RapidArc stereotactic plans showed an acceptable agreement against point and 2D measurements. Both algorithms can therefore be considered safely applicable to stereotactic treatments. PMID- 22047389 TI - A robust and efficient approach to detect 3D rectal tubes from CT colonography. AB - PURPOSE: The rectal tube (RT) is a common source of false positives (FPs) in computer-aided detection (CAD) systems for CT colonography. A robust and efficient detection of RT can improve CAD performance by eliminating such "obvious" FPs and increase radiologists' confidence in CAD. METHODS: In this paper, we present a novel and robust bottom-up approach to detect the RT. Probabilistic models, trained using kernel density estimation on simple low-level features, are employed to rank and select the most likely RT tube candidate on each axial slice. Then, a shape model, robustly estimated using random sample consensus (RANSAC), infers the global RT path from the selected local detections. Subimages around the RT path are projected into a subspace formed from training subimages of the RT. A quadratic discriminant analysis (QDA) provides a classification of a subimage as RT or non-RT based on the projection. Finally, a bottom-top clustering method is proposed to merge the classification predictions together to locate the tip position of the RT. RESULTS: Our method is validated using a diverse database, including data from five hospitals. On a testing data with 21 patients (42 volumes), 99.5% of annotated RT paths have been successfully detected. Evaluated with CAD, 98.4% of FPs caused by the RT have been detected and removed without any loss of sensitivity. CONCLUSIONS: The proposed method demonstrates a high detection rate of the RT path, and when tested in a CAD system, reduces FPs caused by the RT without the loss of sensitivity. PMID- 22047390 TI - Comparison of secondary neutron dose in proton therapy resulting from the use of a tungsten alloy MLC or a brass collimator system. AB - PURPOSE: To apply the dual ionization chamber method for mixed radiation fields to an accurate comparison of the secondary neutron dose arising from the use of a tungsten alloy multileaf collimator (MLC) as opposed to a brass collimator system for defining the shape of a therapeutic proton field. METHODS: Hydrogenous and nonhydrogenous ionization chambers were constructed with large volumes to enable measurements of absorbed doses below 10(-4) Gy in mixed radiation fields using the dual ionization chamber method for mixed-field dosimetry. Neutron dose measurements were made with a nominal 230 MeV proton beam incident on a closed tungsten alloy MLC and a solid brass block. The chambers were cross-calibrated against a (60)Co-calibrated Farmer chamber in water using a 6 MV x-ray beam and Monte Carlo simulations were performed to account for variations in ionization chamber response due to differences in secondary neutron energy spectra. RESULTS: The neutron and combined proton plus gamma-ray absorbed doses are shown to be nearly equivalent downstream from either a closed tungsten alloy MLC or a solid brass block. At 10 cm downstream from the distal edge of the collimating material the neutron dose from the closed MLC was (5.3 +/- 0.4) * 10(- 5) Gy/Gy. The neutron dose with brass was (6.4 +/- 0.7) * 10(- 5) Gy/Gy. Further from the secondary neutron source, at 50 cm, the neutron doses remain close for both the MLC and brass block at (6.9 +/- 0.6) * 10(- 6) Gy/Gy and (6.3 +/- 0.7) * 10(- 6) Gy/Gy, respectively. CONCLUSIONS: The dual ionization chamber method is suitable for measuring secondary neutron doses resulting from proton irradiation. The results of measurements downstream from a closed tungsten alloy MLC and a brass block indicate that, even in an overly pessimistic worst-case scenario, secondary neutron production in a tungsten alloy MLC leads to absorbed doses that are nearly equivalent to those seen from brass collimators. Therefore, the choice of tungsten alloy in constructing the leaves of a proton MLC is appropriate, and does not lead to a substantial increase in the secondary neutron dose to the patient compared to that generated in a brass collimator. PMID- 22047391 TI - Direct dose to water dosimetry for pretreatment IMRT verification using a modified EPID. AB - PURPOSE: Electronic portal imaging devices (EPIDs) are high resolution systems that produce electronic dose maps with minimal time required for equipment setup, and therefore potentially present a time-saving alternative for intensity modulated radiation therapy (IMRT) pretreatment verification. A modified commercial EPID was investigated operated with an opaque sheet blocking the optical signal produced in the phosphor layer as a precursor to a switched mode dual dosimetry-imaging EPID system. The purpose of this study was to investigate the feasibility of using this system for direct dose to water dosimetry for pretreatment IMRT verification. METHODS: A Varian amorphous silicon EPID was modified by placing an opaque sheet between the Gd(2)S(2)O:Tb phosphor layer and the photodiode array to block the optical photons. The EPID was thus converted to a direct-detecting system (dEPID), in which the high energy radiation deposits energy directly in the photodiode array. The copper build-up was replaced with d(max) solid water. Sixty-one IMRT beams of varying complexity were delivered to the EPID, to EDR2 dosimetric film and to a 2D ion chamber array (MapCheck). EPID data was compared to film and MapCheck data using gamma analysis with 3%, 3mm pass criteria. RESULTS: The fraction of points that passed the gamma test was on average 98.1% and 98.6%, for the EPID versus film and EPID versus MapCheck comparisons, respectively. In the case of comparison with film, the majority of observed discrepancies were associated with problems related to film sensitivity or processing. CONCLUSIONS: The very close agreement between EPID and both film and MapCheck data demonstrates that the modified EPID is suitable for direct dose to water measurement for pretreatment IMRT verification. These results suggest a reconfigured EPID could be an efficient and accurate dosimeter. Alternatively, optical switching methods could be developed to produce a dual-mode EPID with both dosimetry and imaging capabilities. PMID- 22047392 TI - Comparison and assessment of semi-automatic image segmentation in computed tomography scans for image-guided kidney surgery. AB - PURPOSE: Image segmentation is integral to implementing intraoperative guidance for kidney tumor resection. Results seen in computed tomography (CT) data are affected by target organ physiology as well as by the segmentation algorithm used. This work studies variables involved in using level set methods found in the Insight Toolkit to segment kidneys from CT scans and applies the results to an image guidance setting. METHODS: A composite algorithm drawing on the strengths of multiple level set approaches was built using the Insight Toolkit. This algorithm requires image contrast state and seed points to be identified as input, and functions independently thereafter, selecting and altering method and variable choice as needed. RESULTS: Semi-automatic results were compared to expert hand segmentation results directly and by the use of the resultant surfaces for registration of intraoperative data. Direct comparison using the Dice metric showed average agreement of 0.93 between semi-automatic and hand segmentation results. Use of the segmented surfaces in closest point registration of intraoperative laser range scan data yielded average closest point distances of approximately 1 mm. Application of both inverse registration transforms from the previous step to all hand segmented image space points revealed that the distance variability introduced by registering to the semi-automatically segmented surface versus the hand segmented surface was typically less than 3 mm both near the tumor target and at distal points, including subsurface points. CONCLUSIONS: Use of the algorithm shortened user interaction time and provided results which were comparable to the gold standard of hand segmentation. Further, the use of the algorithm's resultant surfaces in image registration provided comparable transformations to surfaces produced by hand segmentation. These data support the applicability and utility of such an algorithm as part of an image guidance workflow. PMID- 22047393 TI - Fluorescence diffuse optical tomography using the split Bregman method. AB - PURPOSE: Standard image reconstruction methods for fluorescence Diffuse Optical Tomography (fDOT) generally make use of L2-regularization. A better choice is to replace the L2 by a total variation functional that effectively removes noise while preserving edges. Among the wide range of approaches available, the recently appeared Split Bregman method has been shown to be optimal and efficient. Furthermore, additional constraints can be easily included. We propose the use of the Split Bregman method to solve the image reconstruction problem for fDOT with a nonnegativity constraint that imposes the reconstructed concentration of fluorophore to be positive. METHODS: The proposed method is tested with simulated and experimental data, and results are compared with those yielded by an equivalent unconstrained optimization approach based on Gauss-Newton (GN) method, in which the negative part of the solution is projected to zero after each iteration. In addition, the method dependence on the parameters that weigh data fidelity and nonnegativity constraints is analyzed. RESULTS: Split Bregman yielded a reduction of the solution error norm and a better full width at tenth maximum for simulated data, and higher signal-to-noise ratio for experimental data. It is also shown that it led to an optimum solution independently of the data fidelity parameter, as long as the number of iterations is properly selected, and that there is a linear relation between the number of iterations and the inverse of the data fidelity parameter. CONCLUSIONS: Split Bregman allows the addition of a nonnegativity constraint leading to improve image quality. PMID- 22047394 TI - Automated intraoperative calibration for prostate cancer brachytherapy. AB - PURPOSE: Prostate cancer brachytherapy relies on an accurate spatial registration between the implant needles and the TRUS image, called "calibration". The authors propose a new device and a fast, automatic method to calibrate the brachytherapy system in the operating room, with instant error feedback. METHODS: A device was CAD-designed and precision-engineered, which mechanically couples a calibration phantom with an exact replica of the standard brachytherapy template. From real time TRUS images acquired from the calibration device and processed by the calibration system, the coordinate transformation between the brachytherapy template and the TRUS images was computed automatically. The system instantly generated a report of the target reconstruction accuracy based on the current calibration outcome. RESULTS: Four types of validation tests were conducted. First, 50 independent, real-time calibration trials yielded an average of 0.57 +/ 0.13 mm line reconstruction error (LRE) relative to ground truth. Second, the averaged LRE was 0.37 +/- 0.25 mm relative to ground truth in tests with six different commercial TRUS scanners operating at similar imaging settings. Furthermore, testing with five different commercial stepper systems yielded an average of 0.29 +/- 0.16 mm LRE relative to ground truth. Finally, the system achieved an average of 0.56 +/- 0.27 mm target registration error (TRE) relative to ground truth in needle insertion tests through the template in a water tank. CONCLUSIONS: The proposed automatic, intraoperative calibration system for prostate cancer brachytherapy has achieved high accuracy, precision, and robustness. PMID- 22047395 TI - Flow characteristics in a canine aneurysm model: a comparison of 4D accelerated phase-contrast MR measurements and computational fluid dynamics simulations. AB - PURPOSE: Our purpose was to compare quantitatively velocity fields in and around experimental canine aneurysms as measured using an accelerated 4D PC-MR angiography (MRA) method and calculated based on animal-specific CFD simulations. METHODS: Two animals with a surgically created bifurcation aneurysm were imaged using an accelerated 4D PC-MRA method. Meshes were created based on the geometries obtained from the PC-MRA and simulations using "subject-specific" pulsatile velocity waveforms and geometries were then solved using a commercial CFD solver. Qualitative visual assessments and quantitative comparisons of the time-resolved velocity fields obtained from the PC-MRA measurements and the CFD simulations were performed using a defined similarity metric combining both angular and magnitude differences of vector fields. RESULTS: PC-MRA and image based CFD not only yielded visually consistent representations of 3D streamlines in and around both aneurysms, but also showed good agreement with regard to the spatial velocity distributions. The estimated similarity between time-resolved velocity fields from both techniques was reasonably high (mean value >0.60; one being the highest and zero being the lowest). Relative differences in inflow and outflow zones among selected planes were also reasonable (on the order of 10% 20%). The correlation between CFD-calculated and PC-MRA-measured time-averaged wall shear stresses was low (0.22 and 0.31, p < 0.001). CONCLUSIONS: In two experimental canine aneurysms, PC-MRA and image-based CFD showed favorable agreement in intra-aneurismal velocity fields. Combining these two complementary techniques likely will further improve the ability to characterize and interpret the complex flow that occurs in human intracranial aneurysms. PMID- 22047396 TI - Automatic 3D registration of dynamic stress and rest (82)Rb and flurpiridaz F 18 myocardial perfusion PET data for patient motion detection and correction. AB - PURPOSE: The authors aimed to develop an image-based registration scheme to detect and correct patient motion in stress and rest cardiac positron emission tomography (PET)/CT images. The patient motion correction was of primary interest and the effects of patient motion with the use of flurpiridaz F 18 and (82)Rb were demonstrated. METHODS: The authors evaluated stress/rest PET myocardial perfusion imaging datasets in 30 patients (60 datasets in total, 21 male and 9 female) using a new perfusion agent (flurpiridaz F 18) (n = 16) and (82)Rb (n = 14), acquired on a Siemens Biograph-64 scanner in list mode. Stress and rest images were reconstructed into 4 ((82)Rb) or 10 (flurpiridaz F 18) dynamic frames (60 s each) using standard reconstruction (2D attenuation weighted ordered subsets expectation maximization). Patient motion correction was achieved by an image-based registration scheme optimizing a cost function using modified normalized cross-correlation that combined global and local features. For comparison, visual scoring of motion was performed on the scale of 0 to 2 (no motion, moderate motion, and large motion) by two experienced observers. RESULTS: The proposed registration technique had a 93% success rate in removing left ventricular motion, as visually assessed. The maximum detected motion extent for stress and rest were 5.2 mm and 4.9 mm for flurpiridaz F 18 perfusion and 3.0 mm and 4.3 mm for (82)Rb perfusion studies, respectively. Motion extent (maximum frame-to-frame displacement) obtained for stress and rest were (2.2 +/- 1.1, 1.4 +/- 0.7, 1.9 +/- 1.3) mm and (2.0 +/- 1.1, 1.2 +/-0 .9, 1.9 +/- 0.9) mm for flurpiridaz F 18 perfusion studies and (1.9 +/- 0.7, 0.7 +/- 0.6, 1.3 +/- 0.6) mm and (2.0 +/- 0.9, 0.6 +/- 0.4, 1.2 +/- 1.2) mm for (82)Rb perfusion studies, respectively. A visually detectable patient motion threshold was established to be >=2.2 mm, corresponding to visual user scores of 1 and 2. After motion correction, the average increases in contrast-to-noise ratio (CNR) from all frames for larger than the motion threshold were 16.2% in stress flurpiridaz F 18 and 12.2% in rest flurpiridaz F 18 studies. The average increases in CNR were 4.6% in stress (82)Rb studies and 4.3% in rest (82)Rb studies. CONCLUSIONS: Fully automatic motion correction of dynamic PET frames can be performed accurately, potentially allowing improved image quantification of cardiac PET data. PMID- 22047397 TI - Suitability of miniature inductively coupled RF coils as MR-visible markers for clinical purposes. AB - PURPOSE: MR-visible markers have already been used for various purposes such as image registration, motion detection, and device tracking. Inductively coupled RF (ICRF) coils, in particular, provide a high contrast and do not require connecting wires to the scanner, which makes their application highly flexible and safe. This work aims to thoroughly characterize the MR signals of such ICRF markers under various conditions with a special emphasis on fully automatic detection. METHODS: The small markers consisted of a solenoid coil that was wound around a glass tube containing the MR signal source and tuned to the resonance frequency of a 1.5 T MRI. Marker imaging was performed with a spoiled gradient echo sequence (FLASH) and a balanced steady-state free precession (SSFP) sequence (TrueFISP) in three standard projections. The signal intensities of the markers were recorded for both pulse sequences, three source materials (tap water, distilled water, and contrast agent solution), different flip angles and coil alignments with respect to the B(0) direction as well as for different marker positions in the entire imaging volume (field of view, FOV). Heating of the ICRF coils was measured during 10-min RF expositions to three conventional pulse sequences. Clinical utility of the markers was assessed from their performance in computer-aided detection and in defining double oblique scan planes. RESULTS: For almost the entire FOV (+/-215 mm) and an estimated 82% of all possible RF coil alignments with respect to B(0), the ICRF markers generated clearly visible MR signals and could be reliably localized over a large range of flip angles, in particular with the TrueFISP sequence (0.3 degrees -4.0 degrees ). Generally, TrueFISP provided a higher marker contrast than FLASH. RF exposition caused a moderate heating (<=5 degrees C) of the ICRF coils only. CONCLUSIONS: Small ICRF coils, imaged at low flip angles with a balanced SSFP sequence showed an excellent performance under a variety of experimental conditions and therefore make for a reliable, compact, flexible, and relatively safe marker for clinical use. PMID- 22047398 TI - Development of a human-tissue-like phantom for 3.0-T MRI. AB - PURPOSE: A 3.0-T MRI phantom having human-tissue-equivalent relaxation times was developed. METHODS: The ingredients of the phantom are carrageenan (for gelatinization), GdCl(3) (as a T(1)-relaxation modifier), agarose (as a T(2) relaxation modifier), and NaN(3) (as an antiseptic agent). Numerous samples with varying concentrations of GdCl(3) and agarose were prepared, and T(1) and T(2) were measured using 3.0-T MRI. RESULTS: Relaxation times of the phantom samples ranged from 395 to 2601 ms for T(1) values and 29 to 334 ms for T(2) values. Based on the measured results, empirical formulae were devised to express the relationships between the concentrations of relaxation modifiers and relaxation times. CONCLUSIONS: Adjustment of GdCl(3) and agarose concentrations allows arbitrary setting of relaxation times, and the creation of a phantom that can mimic relaxation times of human-tissue. Carrageenan is considered the most suitable as a gelling agent for an MRI phantom, as it permits the relatively easy and inexpensive production of a large phantom such as for the human torso, and which can be easily shaped with a knife. PMID- 22047399 TI - A few words on evidence based medicine. PMID- 22047400 TI - Multileaf collimators, air gap, lateral penumbra, and range compensation in proton radiotherapy. PMID- 22047401 TI - Direct mechanical measurements reveal the material properties of three dimensional DNA origami. AB - The application of three-dimensional DNA origami objects as rigid mechanical mediators or force sensing elements requires detailed knowledge about their complex mechanical properties. Using magnetic tweezers, we directly measure the bending and torsional rigidities of four- and six-helix bundles assembled by this technique. Compared to duplex DNA, we find the bending rigidities to be greatly increased while the torsional rigidities are only moderately augmented. We present a mechanical model explicitly including the crossovers between the individual helices in the origami structure that reproduces the experimentally observed behavior. Our results provide an important basis for the future application of 3D DNA origami in nanomechanics. PMID- 22047402 TI - RNA-Seq improves annotation of protein-coding genes in the cucumber genome. AB - BACKGROUND: As more and more genomes are sequenced, genome annotation becomes increasingly important in bridging the gap between sequence and biology. Gene prediction, which is at the center of genome annotation, usually integrates various resources to compute consensus gene structures. However, many newly sequenced genomes have limited resources for gene predictions. In an effort to create high-quality gene models of the cucumber genome (Cucumis sativus var. sativus), based on the EVidenceModeler gene prediction pipeline, we incorporated the massively parallel complementary DNA sequencing (RNA-Seq) reads of 10 cucumber tissues into EVidenceModeler. We applied the new pipeline to the reassembled cucumber genome and included a comparison between our predicted protein-coding gene sets and a published set. RESULTS: The reassembled cucumber genome, annotated with RNA-Seq reads from 10 tissues, has 23, 248 identified protein-coding genes. Compared with the published prediction in 2009, approximately 8, 700 genes reveal structural modifications and 5, 285 genes only appear in the reassembled cucumber genome. All the related results, including genome sequence and annotations, are available at http://cmb.bnu.edu.cn/Cucumis_sativus_v20/. CONCLUSIONS: We conclude that RNA-Seq greatly improves the accuracy of prediction of protein-coding genes in the reassembled cucumber genome. The comparison between the two gene sets also suggests that it is feasible to use RNA-Seq reads to annotate newly sequenced or less-studied genomes. PMID- 22047403 TI - Laparoscopic cholecystectomy without handling the cystic artery: a new approach to minimize complications. AB - INTRODUCTION: Although laparoscopy has now become the procedure of choice for removal of gallbladder, complications especially injury to cystic artery and ducts are thought to be higher. We describe a technique that avoids handling and injury of cystic artery and resultant duct injuries. The video length is 2 minutes 13 seconds. MATERIALS AND METHODS: From October 7, 2005, to December 31, 2010, 17 patients were successfully operated by the cystic artery sparing technique. In this technique, dissection begins distal to cystic lymph node on the gallbladder wall using hook cautery, thereby clears the Calot's triangle without even touching the cystic artery. This maneuver eliminates the risk of injuring thus causing bleeding and any subsequent complications. Age, sex, and operative outcomes including follow-ups were evaluated. RESULTS: Age of the patients ranged from 3.4 years to 16 years with an average of 10.12 years. Males were predominant (10:7). Average operative time was 40 minutes. There were no intraoperative or immediate postoperative complications. Patients were allowed feeding 4-6 hours after operation and discharged the following morning. Patients were asked to come for follow-up at 1 week, 1 month, 3 months, 6 months, and 1 year and thereafter yearly. Follow-up period ranged from 6 months to 5 years. There were no operation-related complications other than minor abdominal pain in 3 patients and port-site pain in 2 patients which resolved on conservative treatments. CONCLUSION: During laparoscopic cholecystectomy, if handling of the main cystic artery is avoided then complications of hemorrhage and bile duct injuries can be minimized. PMID- 22047404 TI - Laparoscopic gastric pull-up and thoracoscopic esophago-esophagostomy combined with intrathoracic fundoplication for long-gap pure esophageal atresia. AB - The management of long-gap pure esophageal atresia (LGEA) remains controversial. An 8-month-old girl with LGEA underwent a laparoscopic and thoracoscopic gastric pull-up and esophago-esophagostomy in the right thorax combined with intrathoracic fundoplication. She was positioned supine, and three 5-mm ports were placed in the standard locations for laparoscopic Nissen fundoplication. The gastrostomy was taken down and an additional 5-mm port was inserted at the gastrostomy site. Laparoscopic gastric mobilization was performed; the short gastric and left gastric vessels were divided using harmonic shears, and the whole stomach and distal esophageal stump maintained their vascular supply via the right gastric and gastroepiploic arteries. The hiatus was enlarged by radial incisions at both cruras, and the mobilized whole stomach and distal esophageal stump were pushed up into the right thorax through the hiatus. The patient was placed in a modified prone position and three 5-mm ports were inserted into the right thorax. Via thoracoscopy, the upper esophageal pouch was dissected bluntly, and an esophago-esophagostomy was performed using interrupted 4-0 absorbable sutures and was wrapped by a 360-degree gastric fundoplication. The patient was positioned supine again, and a Heinecke-Mikulicz pyloroplasty and gastropexy were also performed laparoscopically. The patient has mild respiratory distress that requires bronchodilators; however, she is eating baby food well without vomiting. Postoperative intrathoracic gastrofiberscopy showed a well-functioning antireflux valve, and her parents are also satisfied with the cosmetic appearance of the seven small wounds. Our new procedure is feasible and is an excellent option in selected patients with LGEA. PMID- 22047405 TI - Sampling medium side resistance to uptake of semivolatile organic compounds in passive air samplers. AB - Current theory of the uptake of semivolatile organic compounds in passive air samplers (PAS) assumes uniform chemical distribution and no kinetic resistance within the passive sampling media (PSM) such as polystyrene-divinylbenzene resin (XAD) and polyurethane foam (PUF). However, these assumptions have not been tested experimentally and are challenged by some recently reported observations. To test the assumptions, we performed kinetic uptake experiments indoors using cylindrical PSM that had been concentrically segmented into three layers. Both XAD and PUF were positioned in the same type of sampler housing to eliminate the variation caused by the different housing designs, which enabled us to quantify differences in uptake caused by the properties of the PSM. Duplicated XAD (PUF) samples were retrieved after being deployed for 0, 1 (0.5), 2 (1), 4 (2), 8 (4), 12 (8), and 24 (12) weeks. Upon retrieval, the PSM layers were separated and analyzed individually for PCBs. Passive sampling rates (R) were lower for heavier PCB homologues. Within a homologue group, R for XAD was higher than that for PUF, from which we infer that the design of the "cylindrical can" housing typically used for XAD PAS lowers the R compared to the "double bowl" shelter commonly used for PUF-disk PAS. Outer layers of the PSM sequestered much higher levels of PCBs than inner layers, indicative of a kinetic resistance to chemical transfer within the PSM. The effective diffusivities for chemical transfer within PSM were derived and were found negatively correlated with the partition coefficients between the PSM and air. Based on the results, we conclude that the PSM-side kinetic resistance should be considered when investigating factors influencing R and when deriving R based on the loss of depuration compounds. PMID- 22047407 TI - Management of congestive heart failure in dogs. PMID- 22047406 TI - YY1 overexpression is associated with poor prognosis and metastasis-free survival in patients suffering osteosarcoma. AB - BACKGROUND: The polycomb transcription factor Yin Yang 1 (YY1) overexpression can be causally implicated in experimental tumor growth and metastasization. To date, there is no clinical evidence of YY1 involvement in outcome of patients with osteosarcoma. Prognosis of osteosarcoma is still severe and only few patients survive beyond five years. We performed a prospective immunohistochemistry analysis to correlate YY1 immunostaining with metastatic development and survival in a selected homogeneous group of patients with osteosarcoma. METHODS: We studied 41 patients suffering from osteosarcoma (stage II-IVa). Multivariate analysis was performed using Cox proportional hazard regression to evaluate the correlation between YY1 expression and both metastasis development and mortality. RESULTS: YY1 protein is not usually present in normal bone; in contrast, a high number of patients (61%) showed a high score of YY1 positive cells (51-100%) and 39% had a low score (10-50% positive cells). No statistical difference was found in histology, anatomic sites, or response to chemotherapy between the two degrees of YY1 expression. Cox regression analysis demonstrated that the highest score of YY1 expression was predictive of both low metastasis-free survival (HR = 4.690, 95%CI = 1.079-20.396; p = 0.039) and poor overall survival (HR = 8.353, 95%CI = 1.863-37.451 p = 0.006) regardless of the effects of covariates such as age, gender, histology and chemonecrosis. CONCLUSION: Overexpression of YY1 in primary site of osteosarcoma is associated with the occurrence of metastasis and poor clinical outcome. PMID- 22047408 TI - Feline restrictive cardiomyopathy. PMID- 22047409 TI - The neurological examination. PMID- 22047410 TI - Chronic nasal and oral disease in cats. PMID- 22047411 TI - Feline oncology. PMID- 22047412 TI - Cutaneous manifestations and markers of systemic disease. PMID- 22047413 TI - Problem-solving dermatology: Case presentations. PMID- 22047414 TI - Plasma angiotensin II concentrations and the effect of treatment with enalapril in dogs with proteinuria due to renal disease. PMID- 22047416 TI - Stifle surgery. PMID- 22047415 TI - Hepatic arteriovenous fistulas and hepatic portal vein hypoplasia in a labrador retriever. PMID- 22047417 TI - Wound management principles and techniques. PMID- 22047418 TI - Skin flap and skin grafting techinques in small animal surgery. PMID- 22047419 TI - New techniques in small animal reconstructive surgery. PMID- 22047420 TI - Surgical diseases of the perineum. PMID- 22047421 TI - Clinical efficacy of vedaprofen in dogs suffering from disorders of the misculoskeletal system. PMID- 22047422 TI - Voiding urohydropropulsion: An alternative to cystotomy. PMID- 22047423 TI - Diagnostic pitfalls: Misdiagnosing causes of urinary tract signs. PMID- 22047424 TI - Reproductive problems in the bitch and the queen. PMID- 22047425 TI - Nonsurgical retrieval of uroliths for mineral analysis. PMID- 22047426 TI - Progestins and mammary growth hormone production in the dog. PMID- 22047428 TI - Surgery and prognosis in dogs with ectopic ureters. PMID- 22047427 TI - Treatment of urinary incontinence in the bitch: A pilot field study with incurin(r) PMID- 22047429 TI - Cat scratch disease: Studies on diagnosis and identification of reservoirs and vectors. PMID- 22047430 TI - Canine and feline superficial fungal skin infections. PMID- 22047432 TI - Some other virus infections of cats. PMID- 22047431 TI - The role of bordetella bronchiseptica in feline respiratory disease. PMID- 22047433 TI - Prevalence of antibodies against bordetella bronchiseptica in cats with a history of respiratory disease. PMID- 22047434 TI - Comparative study with 5 different distemper vaccines. PMID- 22047436 TI - Surveys on the prevalence of intestinal nematodes in dogs and cats in the Netherlands. PMID- 22047435 TI - Update on the sensitivity of recent European canine and feline pathogens to Marbofloxacin. PMID- 22047437 TI - Radiology and ultrasonography of the urinary tract. PMID- 22047438 TI - Basic principles for interpretation of cytologic preparations. PMID- 22047440 TI - Pituitary-adrenocortical function and glucocorticoid administration in pigeons. PMID- 22047439 TI - Evaluation of environmental enrichment for laboratory mice. PMID- 22047441 TI - Proventriculotomy in 21 ostriches, a retrospective study. PMID- 22047442 TI - The approach to orbital disease in the dog and cat. PMID- 22047443 TI - Feline herpetic ocular disease. PMID- 22047444 TI - Persistent hyperplastic tunica vasculosa lentis and persistent hyaloid artery in a 2-year-old basset hound. PMID- 22047446 TI - Psychosocial stressors and depression at a Swedish primary health care centre. A gender perspective study. AB - BACKGROUND: Psychosocial stress may account for the higher prevalence of depression in women and in individuals with a low educational background. The aim of this study was to analyse the association between depression and socio demographic data, psychosocial stressors and lifestyle circumstances from a gender perspective in a relatively affluent primary care setting. METHODS: Patients, aged 18- 75 years, visiting a drop-in clinic at a primary care health centre were screened with Beck's Depression Inventory (BDI). The physicians used also targeted screening with BDI. A questionnaire on socio-demographic data, psychosocial stressors and use of alcohol and tobacco was distributed. Among patients, who scored BDI >= 10, DSM-IV-criteria were used to diagnose depression. Of the 404 participants, 48 men and 76 women were diagnosed with depression. The reference group consisted of patients with BDI score <10, 187 men and 93 women. Age-adjusted odds ratios (ORs) with 95% confidence intervals (CI) as being depressed were calculated for the psychosocial stressors and lifestyle circumstances, separately for men and women. Multiple logistic regression analyses were used to determine the age-adjusted main effect models for men and women. RESULTS: The same three psychosocial stressors: feeling very stressed, perceived poor physical health and being dissatisfied with one's family situation were associated with depression equally in men and women. The negative predictive values of the main effect models in men and women were 90.7% and 76.5%, respectively. Being dissatisfied with one's work situation had high ORs in both men and women. Unemployment and smoking were associated with depression in men only. CONCLUSIONS: Three questions, frequently asked by physicians, which involve patient's family and working situation as well as perceived stress and physical health, could be used as depression indicators in early detection of depression in men and women in primary health care. PMID- 22047447 TI - Nonvisual arrestins function as simple scaffolds assembling the MKK4-JNK3alpha2 signaling complex. AB - Arrestins make up a small family of proteins with four mammalian members that play key roles in the regulation of multiple G protein-coupled receptor-dependent and -independent signaling pathways. Although arrestins were reported to serve as scaffolds for MAP kinase cascades, promoting the activation of JNK3, ERK1/2, and p38, the molecular mechanisms involved were not elucidated, and even the direct binding of arrestins with MAP kinases was never demonstrated. Here, using purified proteins, we show that both nonvisual arrestins directly bind JNK3alpha2 and its upstream activator MKK4, and that the affinity of arrestin-3 for these kinases is higher than that of arrestin-2. Reconstitution of the MKK4-JNK3alpha2 signaling module from pure proteins in the presence of different arrestin-3 concentrations showed that arrestin-3 acts as a "true" scaffold, facilitating JNK3alpha2 phosphorylation by bringing the two kinases together. Both the level of JNK3alpha2 phosphorylation by MKK4 and JNK3alpha2 activity toward its substrate ATF2 increase at low and then decrease at high arrestin-3 levels, yielding a bell-shaped concentration dependence expected with true scaffolds that do not activate the upstream kinase or its substrate. Thus, direct binding of both kinases and true scaffolding is the molecular mechanism of action of arrestin-3 on the MKK4-JNK3alpha2 signaling module. PMID- 22047448 TI - Salmonella Typhimurium-specific bacteriophage PhiSH19 and the origins of species specificity in the Vi01-like phage family. AB - BACKGROUND: Whole genome sequencing of bacteriophages suitable for biocontrol of pathogens in food products is a pre-requisite to any phage-based intervention procedure. Trials involving the biosanitization of Salmonella Typhimurium in the pig production environment identified one such candidate, PhiSH19. RESULTS: This phage was sequenced and analysis of its 157,785 bp circular dsDNA genome revealed a number of interesting features. PhiSH19 constitutes another member of the recently-proposed Myoviridae Vi01-like family of phages, containing S. Typhi specific Vi01 and Shigella-specific SboM-AG3. At the nucleotide level PhiSH19 is highly similar to phage Vi01 (80-98% pairwise identity over the length of the genome), with the major differences lying in the region associated with host range determination. Analyses of the proteins encoded within this region by PhiSH19 revealed a cluster of three putative tail spikes. Of the three tail spikes, two have protein domains associated with the pectate lyase family of proteins (Tsp2) and P22 tail spike family (Tsp3) with the prospect that these enable Salmonella O antigen degradation. Tail spike proteins of Vi01 and SboM-AG3 are predicted to contain conserved right-handed parallel beta-helical structures but the internal protein domains are varied allowing different host specificities. CONCLUSIONS: The addition or exchange of tail spike protein modules is a major contributor to host range determination in the Vi01-like phage family. PMID- 22047449 TI - Evaluation of microgap size and microbial leakage in the connection area of 4 abutments with Straumann (ITI) implant. AB - A microgap between implant and abutment can lead to mechanical and biological problems such as abutment screw fracture and peri-implantitis. The aim of this study was to evaluate microgap size and microbial leakage in the connection area of 4 different abutments to ITI implants. In this experimental study, 36 abutments in 4 groups (including Cast On, Castable, Solid, and Synocta abutments) connected to Straumann fixtures (with their inner part inoculated with bacterial suspension) and microbial leakage were assessed at different times. The size of the microgap in 4 randomized locations was then measured by scanning electron microscope. The data were analyzed by SPSS software and by 1-way variance statistical test, Kruskal-Wallis, and their supplementary tests (Mann-Whitney HSD and Tukey's; alpha = .05) at the next step. The effect of using different types of abutments was significant on the mean microgap size (P < .001) and on the mean number of leaked colonies (CFU/mL) through the connection area of the implant and abutment within the first 5 hours of the experiment (P = .012); however, it did not significantly influence microleakage at 24 hours, 48 hours, and 14 days (P = .145). Using Synocta abutments compared with Solid abutments will not provide us with more accommodation, and vice versa. Using Solid and Synocta abutments can significantly decrease the microgap size; however, Cast On abutments do not show a significant difference in terms of microgap compared with Castable abutments. Microleakage in the connection area is comparable for these 4 abutments. PMID- 22047450 TI - Age-dependent deterioration of peak inspiratory flow with two kinds of dry powder corticosteroid inhalers (Diskus and Turbuhaler) and relationships with asthma control. AB - BACKGROUND: Inhaled corticosteroid (ICS) therapy has improved the quality of life (QOL) for many asthmatics and reduced mortality rates associated with asthma. However, some patients do not obtain therapeutic benefit despite satisfactory adherence. OBJECTIVES: To determine whether asthmatic patients were using ICS devices appropriately, and to clarify relationships between these results and QOL. SUBJECTS AND METHODS: We studied 100 adult asthmatics, divided into two groups: 50 patients consecutively registered as using Diskus (fluticasone; D group) and 50 consecutively registered as using Turbuhaler (budesonide; T-group). We measured peak inspiratory flows (PIFs) using the In-Check Dial device. Subjects also completed the Asthma Control Test for evaluation of QOL. RESULTS: In the D-group, no patients showed PIF below the optimal range (30-90 L/min), whereas 52% of patients had PIF>=91 L/min. In the T-group, 6% of patients showed PIF over the optimal range (60-90 L/min), and 44% had PIF<=59 L/min. When patients in the T-group were required to deliberately make a maximal inhalation, 14% still had PIF<=59 L/min. The proportion of patients with poor control was significantly greater in the T-group than in the D-group. According to univariate logistic regression analyses, low PIF tended to be associated with poor asthma control in the T-group. No significant correlation was found between PIF and age in the D-group, but PIF decreased significantly with age in the T-group. CONCLUSIONS: Appropriate measures for patients in whom PIF has been judged as lower than optimal include adequate education for inhalation and/or changing to a different inhalation device. These measures should be kept in mind for elderly asthma patients in particular, where appropriate selection of a corticosteroid inhalation device in the early stages of therapy would also be important. PMID- 22047451 TI - Physicians' knowledge of inhaler devices and inhalation techniques remains poor in Spain. AB - BACKGROUND: Studies in many countries in the 1990s revealed deficiencies in physicians' knowledge about inhalation therapy. In an attempt to remedy this situation, Spanish scientific societies implemented a variety of educational strategies. The objective of the present study was to assess changes in attitudes and knowledge about inhalers and inhalation techniques in a sizable sample of physicians. METHODS: An 11-question multiple choice test was developed and administered throughout Spain to practicing physicians from specialties that frequently prescribe inhaler devices. The survey collected demographic characteristics (four items), preferences (two items), and issues related to knowledge (three items) and education (two items) about devices and inhalation techniques. Completion of the questionnaire was voluntary, individual, and anonymous. RESULTS: A total of 1514 respondents completed the questionnaire. Dry powder inhalers (DPI) were preferred by 61.2% physicians, but only 46.1% identified "inhale deeply and forcefully" as the most significant step in the inhalation maneuver using these devices. Only 27.7% stated that they always checked the patient's inhalation technique when prescribing a new inhaler. A composite variable, general inhaled therapy knowledge, which pooled the correct answers related to knowledge, revealed that only 14.2% physicians had an adequate knowledge of inhaled therapy. Multivariate analysis showed that this knowledge was lowest among internal medicine and primary care physicians. CONCLUSIONS: Prescribers' knowledge of inhalers and inhalation techniques remains poor in Spain. The causes should be identified in further research to allow effective educational strategies to be developed. Specific educational policies should be addressed to general practitioners. PMID- 22047452 TI - Dietary fat intake and quality of life: the SUN project. AB - BACKGROUND: Few studies have related nutritional factors with quality of life in healthy populations. The purpose of the study was to assess whether dietary fat intake is associated to mental and physical quality of life. METHODS: This analysis included 8,430 participants from the SUN (Seguimiento Universidad de Navarra) Project. The intake of saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), trans unsaturated fatty acids (TFA), and monounsaturated fatty acids (MUFA) was assessed through a 136-item food frequency questionnaire at baseline. Quality of life was measured with the SF-36 Health Survey after 4 years of follow-up. Generalized Linear Models were fitted to assess the regression coefficients (b) and their 95% confidence intervals (95% CI) for the 8 domains of the SF-36 according to successive quintiles of each kind of fatty acids intake. RESULTS: The multivariate-adjusted models revealed a significant inverse association for SFA intake (in quintiles) and two of the physical domains (physical functioning and general health). E.g. for general health domain: (highest quintile of intake (Q5) vs. lowest quintile (Q1), b = -1.6; 95% CI = 3.1, -0.1. General health also showed a dose-response relationship (p for trend < 0.05). For TFA intake (in quintiles), a significant inverse association was found for most of the mental domains (vitality, social functioning and role emotional). E.g. for vitality domain (Q5) vs. (Q1), b = -2.0, 95% CI = -3.4 to -0.6. We also found an inverse association between TFA intake and the bodily pain domain: (Q5 vs. Q1), b = -2.6; 95% CI = -4.4 to -0.8, with a statistically significant dose response relationship (p for trend < 0.05). Except for TFA intake and the mental domains, the rest of the associations were attenuated when we repeated the analysis adjusting for adherence to the Mediterranean diet. CONCLUSIONS: A detrimental relationship between TFA intake at baseline and most of the SF-36 mental domains measured 4 years later were found, whereas weak inverse associations were found for SFA intake and some physical domains. PMID- 22047453 TI - Quantifying protein-protein interactions within noncovalent complexes using electrospray ionization mass spectrometry. AB - Several electrospray-mass spectrometry (ESI-MS)-based methods are available for determining the constant of association (K(a)) between a protein and a small ligand, but current MS-based strategies are not fully adequate for measuring K(a) of protein-protein interactions accurately. We expanded the application of ESI-MS based titration to determine the strength of noncovalent interactions between proteins, forming a complex. Taking into account relative response factors (probability of being ionized, transmitted, and detected), we determined K(a) values of an equilibrium between dimers and tetramers at three different pH values (6.8, 3.4, and 8.4). We investigated the association of the lectin concanavalin A, whose dimer-tetramer ratio in the gas phase is affected by solution concentration and by pH. To calculate the constants of association in solution, we also utilized isothermal titration calorimetry (ITC) for a comparison with MS-based titration. At pH 6.8 and pH 8.4, the K(a) values measured by MS and by ITC were in agreement. ITC results allowed us to restrain the response factor to a value close to 4. At pH 3.4, we were able to measure the K(a) only by MS, but not by ITC because of limited sensitivity of calorimetry. Our investigation illustrates the great potential MS for calculating the binding strength of protein-protein interactions within noncovalent complexes. The main advantages of MS over ITC are its sensitivity (i.e., the required amount of sample is >100 times less than the one necessary for ITC), and the possibility to obtain precise information on composition of protein complexes, their stoichiometry, their subunit interactions, and their assembly pathway. Compared to previous investigations, our study shows the strong influence of response factors on determining accurate protein-protein association constants by MS. PMID- 22047454 TI - Information processing speed, neural efficiency, and working memory performance in multiple sclerosis: differential relationships with structural magnetic resonance imaging. AB - Multiple sclerosis (MS), a central nervous system (CNS) neurodegenerative disorder, involves lesions of both white and gray matter and reported cognitive impairments that include processing speed (PS), executive function, and working memory (WM). This study closely examined the specifics of these cognitive deficits and their relationship to structural brain damage. A visual n-back task with 3 WM load conditions was used to assess WM performance (task accuracy), PS (reaction time, RT), and a novel measure of processing efficiency (standard deviation of RT, RTSD) in MS patients and controls. These behavioral measures were related to quantitative magnetic resonance imaging (MRI) measures of white and gray matter integrity. Even when MS patients performed as well as controls, as seen for low WM load (0-back), they responded more slowly and were less efficient in their speed of responding. Accuracy findings indicated that the correct match trials were superior to correct nonmatch trials at differentiating MS patients from controls. Further, decreased accuracy during the highest WM load condition was associated with global damage that included both gray and white matter atrophy, while slowed PS and particularly processing inefficiency were associated primarily with white matter atrophy in MS. Importantly, relationships between PS, processing efficiency, performance accuracy, and structural MRI measures were seen only during the highest WM load condition, the condition that required the most executive control. These findings suggest that the MRI/behavioral relationships that were present exclusively during the 2-back condition may reflect connectivity involving frontal cortical systems, the site for executive control. PMID- 22047455 TI - General pathway toward crystalline-core micelles with tunable morphology and corona segregation. AB - We present a general mechanism for the solution self-assembly of crystalline-core micelles (CCMs) from triblock copolymers bearing a semicrystalline polyethylene (PE) middle block. This approach enables the production of nanoparticles with tunable dimensions and surface structures. Depending on the quality of the solvent used for PE, either spherical or worm-like CCMs can be generated in an easy and highly selective fashion from the same triblock copolymers via crystallization-induced self-assembly upon cooling. If the triblock copolymer stays molecularly dissolved at temperatures above the crystallization temperature of the PE block, worm-like CCMs with high aspect ratios are formed by a nucleation and growth process. Their length can be conveniently controlled by varying the applied crystallization temperature. If exclusively spherical micelles with an amorphous PE core are present before crystallization, confined crystallization within the cores of the preformed micelles takes place and spherical CCMs are formed. For polystyrene-block-polyethylene-block-poly(methyl methacrylate) triblock terpolymers a patch-like microphase separation of the corona is obtained for both spherical and worm-like CCMs due to the incompatibility of the PS and PMMA blocks. The structure of the patch-like corona depends on the selectivity of the employed solvent for the PS and PMMA corona blocks, whereby nonselective solvents produce a more homogeneous patch size and distribution. Annealing of the semicrystalline PE cores results in an increasingly uniform crystallite size distribution and thus core thickness of the worm-like CCMs. PMID- 22047457 TI - FTIR and UV spectroscopy in real-time monitoring of S. cerevisiae cell culture. AB - A combination of FTIR and UV spectroscopy is proposed as a novel technique for integrated real-time monitoring of metabolic activity and growth rates of cell cultures, required for systematic studies of cellular low-frequency (LF) electric and magnetic field (EMF) effects. As an example, we investigated simultaneous influence of periodic LF 3D EMFs on a culture of Saccharomyces cerevisiae (baker's yeast) cells. Amplitudes, frequencies and phases of the field components were the variable parameters. Electromagnetic fields were found to efficiently control the activity of the yeast cells, with the resulting CO(2) production rates, as monitored by FTIR spectroscopy, varying by at least one order of magnitude due to the field action. Additionally, population dynamics of the yeast cells was monitored by UV absorption of the yeast culture at lambda(prob) = 320 nm, and compared to the CO(2) production rates. The detected physiologically active frequencies are all below 1 kHz, namely, 800 Hz excitation was effective in reducing the metabolic rates and arresting cell proliferation, whereas 200 Hz excitation was active in accelerating both cell proliferation and overall metabolic rates. The proposed methods produce objective, reliable and quantitative real-time results within minutes and may be used in various tasks that could benefit from a rapid feedback they provide in the form of metabolic and growth rates. Amplitude and frequency dependences of the LF EMF effects from individual field components with different polarizations were recorded and qualitatively interpreted based on a simple model, describing ion diffusion through a membrane channel. PMID- 22047458 TI - Planarian activity differences when maintained in water pre-treated with magnetic fields: a nonlinear effect. AB - There have been multiple claims that exposing water to a static magnetic field affects its properties which influence living systems. To test this hypothesis, planarian subsequent to dissection were maintained in spring water that had been previously exposed for only one day to one of three (16, 160, or 1,600 G) intensity static magnetic fields or to a reference condition. Although there was no significant difference in regeneration rates over the subsequent seven-day period, there was a statistically significant nonlinear effect for planarian mobility and diffusion rates. Both mobility rates and diffusion velocity of a liquid within the water that had been exposed to the 16 G field was about twice that for water exposed to the other intensities. These results imply that nonlinear biophysical effects may emerge under specific conditions of intensity ranges for particular volumes of water. PMID- 22047459 TI - MnSOD expression inhibited by electromagnetic pulse radiation in the rat testis. AB - Male Sprague Dawley rats were exposed to EMP irradiation of 100 kV/m peak-to-peak e-field intensity and different numbers of pulses. Rat sperm samples were prepared for analysis of sperm qualities; Testes were assessed by transmission electron microscopy and serum hormone concentrations were examined by radioimmunoassay; Enzymatic activities of Total-superoxide dismutase(T-SOD) and manganese-superoxide dismutase (MnSOD), the mRNA levels of MnSOD and cuprozinc superoxide dismutase (CuZnSOD), and the density of malondialdehyde (MDA) were also determined. EMP irradiation did not affect spermatozoon morphology, micronucleus formation rate, sperm number or viability, but the acrosin reaction rate decreased at 24 h and 48 h and recovered by 72 h after irradiation as compared to the controls. The ultrastructure of rat testis displayed more serious damage at 24 h than at other time points (6 h, 12 h, 48 h). Serum levels of luteotrophic hormone (LH) and testosterone (T) were elevated in irradiated rats as compared to controls. After irradiation, enzymatic activities of T-SOD and MnSOD were reduced by 24 h, consistent with the changes observed in MnSOD mRNA expression; MDA content increased at 6 h in turn. These studies have quantified the morphological damage and dysfunction in the rat reproductive system induced by EMP. The mechanism of EMP induced damage may be associated with the inhibition of MnSOD expression. PMID- 22047460 TI - 900-MHz microwave radiation promotes oxidation in rat brain. AB - Recently, there have been several reports referring to detrimental effects due to radio frequency electromagnetic fields (RF-EMF) exposure. Special attention was given to investigate the effect of mobile phone exposure on the rat brain. Since the integrative mechanism of the entire body lies in the brain, it is suggestive to analyze its biochemical aspects. For this, 35-day old Wistar rats were exposed to a mobile phone for 2 h per day for a duration of 45 days where specific absorption rate (SAR) was 0.9 W/Kg. Animals were divided in two groups: sham exposed (n = 6) and exposed group (n = 6). Our observations indicate a significant decrease (P < 0.05) in the level of glutathione peroxidase, superoxide dismutase, and an increase in catalase activity. Moreover, protein kinase shows a significant decrease in exposed group (P < 0.05) of hippocampus and whole brain. Also, a significant decrease (P < 0.05) in the level of pineal melatonin and a significant increase (P < 0.05) in creatine kinase and caspase 3 was observed in exposed group of whole brain as compared with sham exposed. Finally, a significant increase in the level of ROS (reactive oxygen species) (P < 0.05) was also recorded. The study concludes that a reduction or an increase in antioxidative enzyme activities, protein kinase C, melatonin, caspase 3, and creatine kinase are related to overproduction of reactive oxygen species (ROS) in animals under mobile phone radiation exposure. Our findings on these biomarkers are clear indications of possible health implications. PMID- 22047461 TI - Numerical sensitivity modeling for the detection of skin tumors by using tetrapolar probe. AB - The measurement of electrical impedance of skin using surface electrodes permits the assessment of changes in local properties of the skin and can be used in the detection of tumors. The sensitivity of this technique depends mainly on the geometry of the probe and the size of the tumor. In this article, the impedance method was used to estimate the sensitivity of a tetrapolar probe in detecting small regions of increased conductivity in a stratified model of human skin. The impedance method was used to model the potential distribution using fasorial analysis to solve the node equations of the equivalent circuit. Interpolation was applied to reduce discretization error. The skin was modeled as a three-layer structure with different conductivity and permittivity obtained from the literature. A tumor was modeled as a small volume with admittivity four times higher than the normal tissue. Sensitivity calculation was made as a function of electrode diameter and separation, tumor size, and excitation frequency. The simulations indicated that by inserting a one square millimeter tumor in the epidermis, the load impedance to the current source varies about 1% while the transfer impedance varied 8%. The sensitivity also increases nonlinearly with increasing tumor area and thickness. Additionally, it was found that the sensitivity of the transfer impedance has a maximum value when the electrodes are separated by 1.8 mm. The results show that transfer impedance measurements of the skin may detect small skin tumors with a reasonable sensitivity by using an appropriate tetrapolar probe. PMID- 22047462 TI - Analysis of DNA fragmentation in mouse embryos exposed to an extremely low frequency electromagnetic field. AB - Effects of extremely low-frequency electromagnetic fields (ELF-EMFs) on DNA damage in biological systems are still a matter of dispute. The aim of the present study was to investigate the possible effect of electromagnetic field exposure on DNA fragmentation in cells (blastomers) of mouse blastocysts. Eighty female NMRI mice were randomly divided into 2 groups of 40 animals each. The control group was left unexposed whereas the animals in the EMF-group were exposed to a 50-Hz EMF at 0.5 mT 4 h per day, 6 days a week for a duration of 2 weeks. After the 8(th) day of exposure, the female mice in both groups were superovulated (with injections of pregnant mare serum gonadotropin and human chorionic gonadotropin) and then mated overnight. At approximately 4 days after mating (102 h after the human chorionic gonadotropin treatment), blastocysts were obtained by flushing the uterus horns. The mean numbers of pregnant mice, blastocysts after flushing, blastomers within the blastocysts, and the DNA fragmentation index following staining in both groups were compared using statistical methods (SPSS, the Chi-square test, the Student's t-test and the Mann Whitney U-test, P < 0.05). The results showed that the mean number of blastocysts after flushing was significantly decreased in the EMF-group compared to that of the control group (P < 0.03). The DNA fragmentation index was significantly increased in the EMF-group compared to control (10.53% vs. 7.14%; P < 0.001). However, there was no significant difference in the mean numbers of blastomers and numbers of pregnant mice between the EMF-exposed and control group. Our findings indicate that the EMF exposure in preimplantation stage could have detrimental effects on female mouse fertility and embryo development by decreasing the number of blastocysts and increasing the blastocysts DNA fragmentation. PMID- 22047463 TI - Effects of radiofrequency radiation exposure on blood-brain barrier permeability in male and female rats. AB - During the last several decades, numerous studies have been performed aiming at the question of whether or not exposure to radiofrequency radiation (RFR) influences the permeability of the blood-brain barrier (BBB). The objective of this study was to investigate the effect of RFR on the permeability of BBB in male and female Wistar albino rats. Right brain, left brain, cerebellum, and total brain were analyzed separately in the study. Rats were exposed to 0.9 and 1.8 GHz continuous-wave (CW) RFR for 20 min (at SARs of 4.26 mW/kg and 1.46 mW/kg, respectively) while under anesthesia. Control rats were sham-exposed. Disruption of BBB integrity was detected spectrophotometrically using the Evans blue dye, which has been used as a BBB tracer and is known to be bound to serum albumin. Right brain, left brain, cerebellum, and total brain were evaluated for BBB permeability. In female rats, no albumin extravasation was found in in the brain after RFR exposure. A significant increase in albumin was found in the brains of the RF-exposed male rats when compared to sham-exposed male brains. These results suggest that exposure to 0.9 and 1.8 GHz CW RFR at levels below the international limits can affect the vascular permeability in the brain of male rats. The possible risk of RFR exposure in humans is a major concern for the society. Thus, this topic should be investigated more thoroughly in the future. PMID- 22047464 TI - Selection of suitable reference genes from bone cells in large gradient high magnetic field based on GeNorm algorithm. AB - Studies of animals and humans subjected to spaceflight demonstrate that weightlessness negatively affects the mass and mechanical properties of bone tissue. Bone cells could sense and respond to the gravity unloading, and genes sensitive to gravity change were considered to play a critical role in the mechanotransduction of bone cells. To evaluate the fold-change of gene expression, appropriate reference genes should be identified because there is no housekeeping gene having stable expression in all experimental conditions. Consequently, expression stability of ten candidate housekeeping genes were examined in osteoblast-like MC3T3-E1, osteocyte-like MLO-Y4, and preosteoclast like FLG29.1 cells under different apparent gravities (MUg, 1 g, and 2 g) in the high-intensity gradient magnetic field produced by a superconducting magnet. The results showed that the relative expression of these ten candidate housekeeping genes was different in different bone cells; Moreover, the most suitable reference genes of the same cells in altered gravity conditions were also different from that in strong magnetic field. It demonstrated the importance of selecting suitable reference genes in experimental set-ups. Furthermore, it provides an alternative choice to the traditionally accepted housekeeping genes used so far about studies of gravitational biology and magneto biology. PMID- 22047466 TI - Effect of an institutional development plan for user participation on professionals' knowledge, practice, and attitudes. A controlled study. AB - BACKGROUND: Governments in several countries attempt to strengthen user participation through instructing health care organisations to plan and implement activities such as user representation in administrational boards, improved information to users, and more individual user participation in clinical work. The professionals are central in implementing initiatives to enhance user participation in organisations, but no controlled studies have been conducted on the effect on professionals from implementing institutional development plans. The objective was to investigate whether implementing a development plan intending to enhance user participation in a mental health hospital had any effect on the professionals' knowledge, practice, or attitudes towards user participation. METHODS: This was a non-randomized controlled study including professionals from three mental health hospitals in Central Norway. A development plan intended to enhance user participation was implemented in one of the hospitals as a part of a larger re-organizational process. The plan included i.e. establishing a patient education centre and a user office, purchasing of user expertise, appointing contact professionals for next of kin, and improving of the centre's information and the professional culture. The professionals at the intervention hospital thus constituted the intervention group, while the professionals at two other hospitals participated as control group. All professionals were invited to answer the Consumer Participation Questionnaire (CPQ) and additional questions, focusing on knowledge, practice, and attitudes towards user participation, two times with a 16 months interval. RESULTS: A total of 438 professionals participated (55% response rate). Comparing the changes in the intervention group with the changes in the control group revealed no statistically significant differences at a 0.05 level. The implementation of the development plan thus had no measurable effect on the professionals' knowledge, practice, or attitudes at the intervention hospital, compared to the control hospitals. CONCLUSION: This is the first controlled study on the effect on professionals from implementing a development plan to enhance user participation in a mental health hospital. The plan had no effect on professionals' knowledge, practice, or attitudes. This can be due to the quality of the development plan, the implementation process, and/or the suitability of the outcome measures. PMID- 22047467 TI - Solvent evaporation induced aggregating assembly approach to three-dimensional ordered mesoporous silica with ultralarge accessible mesopores. AB - A solvent evaporation induced aggregating assembly (EIAA) method has been demonstrated for synthesis of highly ordered mesoporous silicas (OMS) in the acidic tetrahydrofuran (THF)/H(2)O mixture by using poly(ethylene oxide)-b poly(methyl methacrylate) (PEO-b-PMMA) as the template and tetraethylorthosilicate (TEOS) as the silica precursor. During the continuous evaporation of THF (a good solvent for PEO-b-PMMA) from the reaction solution, the template molecules, together with silicate oligomers, were driven to form composite micelles in the homogeneous solution and further assemble into large particles with ordered mesostructure. The obtained ordered mesoporous silicas possess a unique crystal-like morphology with a face centered cubic (fcc) mesostructure, large pore size up to 37.0 nm, large window size (8.7 nm), high BET surface area (508 m(2)/g), and large pore volume (1.46 cm(3)/g). Because of the large accessible mesopores, uniform gold nanoparticles (ca. 4.0 nm) can be introduced into mesopores of the OMS materials using the in situ reduction method. The obtained Au/OMS materials were successfully applied to fast catalytic reduction of 4-nitrophenol in the presence of NaHB(4) as the reductant. The supported catalysts can be reused for catalytic reactions without significant decrease in catalysis performance even after 10 cycles. PMID- 22047469 TI - The role of triplet state keto-enol tautomerism in the photodeamination of metamitron. AB - Substituted 4-amino-1,2,4-triazin-5-ones undergo photodeamination through cleavage of the N-NH(2) bond in the presence of oxygen and water. To elucidate the mechanism of this reaction, we investigated the photolysis of metamitron (4 amino-6-phenyl-3-methyl-1,2,4-triazin-5-one) by nanosecond laser flash photolysis, steady-state irradiation, and ab initio calculations. Upon pulsed laser excitation of deoxygenated aqueous metamitron, two transient species are clearly detected. The predictions of ab initio results are consistent with experimental results: (i) it is proposed here that the transient species are, respectively, the keto and diradical forms of the metamitron keto-enol tautomerism in the triplet state, and (ii) in water, the activation free energy barrier of enolization is drastically decreased. Thus, the formation of the diradical triplet is enabled in aqueous solvent. A detailed analysis of the intermediate structures that lead to the final products (HNO(2) and deaminometamitron) is provided. PMID- 22047468 TI - A patient with amyotrophic lateral sclerosis and atypical clinical and electrodiagnostic features: a case report. AB - INTRODUCTION: Amyotrophic lateral sclerosis is a rapidly progressive, fatal neurodegenerative disorder for which there is no effective treatment. The diagnosis is dependent on the clinical presentation and consistent electrodiagnostic studies. Typically, there is a combination of upper and lower motor neuron signs as well as electrodiagnostic studies indicative of diffuse motor axonal injury. The presentation of amyotrophic lateral sclerosis, however, may be variable. At the same time, the diagnosis is essential for patient prognosis and management. It is therefore important to appreciate the range of possible presentations of amyotrophic lateral sclerosis. CASE PRESENTATION: We present the case of a 57-year-old Caucasian man with pathological findings on postmortem examination consistent with amyotrophic lateral sclerosis but atypical clinical and electrodiagnostic features. He died after a rapid course of progressive weakness. The patient did not respond to immunosuppressive therapy. CONCLUSION: Amyotrophic lateral sclerosis should be considered in patients with a rapidly progressive, unexplained neuropathic process. This should be true even if there are atypical clinical and electrodiagnostic findings. Absence of response to therapy and the development of upper motor neuron signs should reinforce the possibility that amyotrophic lateral sclerosis may be present. Since amyotrophic lateral sclerosis is a fatal illness, however, the possibility of this disease in patients with atypical clinical features should not diminish the need for a thorough diagnostic evaluation and treatment trials. PMID- 22047471 TI - From idealistic helper to enterprising learner: critical reflections on personal development through experiences from Afghanistan. AB - There is little written about the cultural, social, and ethical challenges encountered by physiotherapists engaging in development work. This article takes a critical perspective on what it means to engage in development work as an expatriate physiotherapist, through a self-critical reflection on experiences from Afghanistan. The field notes from an ethnographic study of a development project conducted in Afghanistan were analysed to explore the transformative process of personal and professional development of the development worker. The critical reflective process entailed a change in meaning perspective, described as a shift from the position of an Idealistic Helper to an Enterprising Learner. Of importance in this process were "disorienting dilemmas" that challenged personal perceptions. Critical reflection over such dilemmas led to deeper understanding facilitating the process of change. The essential lesson learned is that the baseline for understanding others is an understanding of one's own meaning perspectives and manner of participation in relation to others and their context. The insights gained have implications for physiotherapists working in development contexts, for other development workers, and for physiotherapists working with patients in clinical practice in a nondevelopment context. Exploring how to collaborate in development contexts could be done using reflective groups with expatriate and local physiotherapists and/or patients. This could lead to greater understanding of oneself, each other, and the local context. PMID- 22047472 TI - Chemical vapor deposition synthesis of tunable unsubstituted polythiophene. AB - Despite having exceptional electroactive properties, applications of unsubstituted polythiophene (PTh) have been limited due to its insolubility. To overcome this challenge, we have employed oxidative chemical vapor deposition (oCVD) as a unique liquid-free technique to enable the oxidative polymerization of PTh using thiophene as the starting monomer and vanadium oxytrichloride as an effective vaporizable oxidant initiator. Vibrational and phototelectron spectroscopy indicated the formation of unsubstituted polythiophene. Cyclic voltammetry revealed its electrochromic behavior in solution. Significantly, polymer conjugation length and electrical conductivity can be tuned by controlling oCVD process variables. Polymerization is found to be adsorption limited, so by providing sufficient monomer and limiting the amount of initiator at the growth surface, PTh is believed to be formed through alpha-alpha thiophene linkages. PMID- 22047473 TI - ERRATUM. PMID- 22047477 TI - Structural optimization of Cu-Ag-Au trimetallic clusters by adaptive immune optimization algorithm. AB - The putative global minimum structures of Cu-Ag-Au trimetallic clusters with 19 and 55 atoms are obtained by adaptive immune optimization algorithm (AIOA) with the Gupta potential. For the 19-atom trimetallic clusters, the results indicate that all of them have double-icosahedral motifs. For the optimized structures of Cu(13)Ag(n)Au(42-n) (n = 1-41), the clusters can be categorized into 19 Mackay icosahedral structures, 1 6-fold pancake structure, and 21 ring-like structures linked by three face-sharing double-icosahedra. Furthermore, the segregation phenomena of the Cu, Ag, and Au atoms in the Cu-Ag-Au trimetallic clusters are studied to provide useful information for geometric character. Results show that Cu and Ag atoms prefer to locate in the inner-shell and on the surface, respectively, whereas Au atoms mainly locate in the middle-shell and tend to solve into Cu and Ag atoms. PMID- 22047478 TI - Science convention "Rijeka and its Citizens in Medical History" 2000-2009 - history of medicine as a component of scientific visibility. AB - This paper analyses the form and content of the first ten science conventions "Rijeka and its Citizens in Medical History" ("Rijeka i Rijecani u medicinskoj povjesnici") which were held in the period between 2000 and 2009 according to the archive data of the convention organizers Croatian Scientific Society for the History of Health Culture. It presents data on the inception of the idea of a science convention, its organisational features (organising committees, presiding committees, convention topics, venue, patrons) and number of participants. A total of 174 presentations whose abstracts were published in individual Convention Collections were given at the ten conventions by 103 different authors from Croatia and neighbouring countries. After the first ten years the entire material was compiled and published with an analytical comment in the anniversary issue Znanstveni skup Rijeka i Rijecani u medicinskoj povjesnici 2000-2009 (Scientific Convention Rijeka and its Citizens in Medical History 2000-2009) within Biblioteka AMHA. Most of the papers printed in extenso are published in the magazine AMHA - Acta medico historica Adriatica. The analysis of all presentations provides quantity data on the number of presented papers, number of presenters and number of co-authored papers, as well as quality determinants within the evaluation of the achievement of science convention objectives. The end gives a review of the significance of this convention within the regional, national and international aspect. PMID- 22047479 TI - Apothecary activity in Dubrovnik Dominican Monastery from 17th to the beginning 19th century. AB - The origin of the Dominican monastery pharmacy is not clear, but sources suggest that it had operated from the eve of the great earthquake in Dubrovnik in 1667 to the beginning of the 19th century. Its last pharmacist, praised for his competence, passed away in 1803, leaving no one behind The prior travelled all the way to Naples to find a competent pharmacist in his stead, but never returned. Story has it that on the way back, the abbot and the pharmacist lost their lives in a shipwreck. The French army occupied the town in 1806, and the monastery was turned into a military camp. Following the retreat of the French army in 1814, the monastery was returned to the Dominicans, but the pharmacy was never restored. PMID- 22047480 TI - [Vampires in the village Zrnovo on the island of Korcula: following an archival document from the 18th century]. AB - The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de' Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village zrnove on the island of Korcula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions. PMID- 22047481 TI - Health Resort Opatija Volunteer Fire Brigade and Rescue Society. AB - Not only the health service but also several other humanitarian institutions and societies were active in Abbazia/Opatija, the most important town on the once Austrian Riviera, the town that was also known as the Austrian Nice. The most important of the societies was The Health Resort Opatija Volunteer Fire Brigade and Rescue Society. The authors of this article have been particularly interested in the society's founding and its activity until it moved into the new building at 6, St. Florjan's Street in 1910. The fast urbanisation and the development of the industry raised the need of the well organised activity of putting out fires. The German gymnastics societies were the first to include the education and the skills development of the volunteer firemen into their programmes. The first volunteer fire brigades appeared in Austria after 1863. The huge fire that broke out in Vienna in 1881 showed that the fast and efficient rescuing demanded a well prepared organization of a team of rescuers. Based on the initiative of the chimney sweep Franz Drescher and The South Railway Company, the volunteer fire brigade was founded in Opatija already in 1886. The founding of the volunteer rescue society was based on the idea given by dr. Jaromir Mundy, the permanent guest in Opatija and a friend of prof. dr. Theodor Billroth, in 1894. The intertwining activity of the both societies resulted in their formal joining. The head physician became dr. Franz Tripold, the chief commander was Franz Doberlet junior. For his special merits, the general assembly of the Health Resort Opatija Volunteer Fire Brigade and Rescue Society appointed him the honourable commander of the society in 1903 and he received a special photo album with the photos of the volunteer firemen and the rescuers' practice. The Emperor Franz Joseph I Jubilee Fire Station, the Rescue Station And the Sanatorium (Kaiser Franz Joseph I Jubilaums - Feuerwehrrustungshaus, Rettungsstation und Erholungsheim) was given to the use on 1st October 1910. Since then, the two societies worked at this same location. The Volunteer Fire Brigade Opatija has been located in this building ever since. PMID- 22047482 TI - [Dr Anto Maric (1897-1982): a journey from alcohology and dermatovenereology to psychiatry and balneology]. AB - Dr Anto Maric (1897-1982) was born in Vuksic in Bosnia. He completed medical studies in Vienna and Prague. He published his results from the Department for dermatovenerology at Sarajevo State Hospital, Bosnia. He engaged himself in the movement against alcoholism, too. Later he moved to the Neuropsychiatry ward in Belgrade and was appointed manager in a new psychiatry hospital in Kovin, Serbia. For years he had been a community physician in Stanisic in Vojvodina. During the Second World War, he worked in the psychiatric hospital Vrapce at the outskirts of Zagreb, Croatia and after the war he became the head of a thermal spa in Srebrenica, Bosnia. After specialisation in balneology, he came to Rijeka to overlook the reconstruction of a thermal spa near Buzet in Istria. He made use of his long experience in dermatovenerology, neuropsychiatry and balneology to promote the importance of the unity between physical and psychological for maintaining human health. PMID- 22047483 TI - Gout in the writings of eminent ancient Greek and Byzantine physicians. AB - Gout is a medical condition with typical recurrent attacks of acute inflammatory arthritis. The severity of this illness has been recognised from antiquity, and several ancient physicians studied it intensively. This paper presents the pathogenesis of the disease, approaches to therapy and preventive measures based on a number of original medical scripts from Hippocrates to the end of the Byzantine era. PMID- 22047484 TI - Rufus of Ephesus and his contribution to the development of anatomical nomenclature. AB - Rufus of Ephesus, a famous ancient physician, lived about the years 80 - 150 CE. His theories stressed the importance of anatomy and he preferred pragmatic approach to diagnosis and treatment. In his work "On the Names of the Parts of the Human Body", he put in pragmatic effort to make a lexicon of anatomy for his pupils. In the introduction, he described it as a manual for the students of medical art which relied on demonstration in teaching; visible (outer) parts of the body were shown on a demonstrator and invisible (inner) parts were shown on a dissected monkey. The brief explanation of the anatomical terms includes position, shape, and functions of organs, and this is what makes his work a pioneering effort to explain the anatomy clearly, systematically, and using consistent terminology. Rufus stressed the importance of exact nomenclature to prevent misunderstandings in medical practice. This anatomy manual had a major influence on the development of anatomical terminology. It is an important contribution to the history of teaching. The other essential contribution of Rufus' lexicon (also known for its briefer title Onomastikon) is that the author recognised and critically reviewed the knowledge and views of his predecessors, physicians of the pre-Galenic period. No less important was his teaching to anatomists and physicians who followed, as they often cited or paraphrased Rufus in their own works (Galen, Oribasius). Many fragments of Rufus' work have been preserved by medieval Arabic medical writers, especially by Rhazes. PMID- 22047485 TI - [Dr Stanislav Zupic (1897-1973) - a remarkable figure in Croatian psychiatry]. AB - Stanislav Zupic (1897-1973) spent most of his career (1920-1962) in the Psychiatric Hospital Vrapce, Zagreb, Croatia and was its 8th director from 1940 to 1941. He is remembered by a number innovations in treating psychoses, by a pioneering Croatian psychodrama (in 1938, he published a play Coming back to Life), and by introducing bibliotherapy, musical therapy, art therapy, and homeopathy to treat mental illnesses. On his initiative, the psychiatric hospital introduced treatment with insulin-provoked comma, convulsive therapy, Largactil, and other state-of-the-art psychopharmaceuticals. In addition to treatment, he provided forensic expertise. His free time he would spend writing pathographies of artists and literary critics. In 1924, he was one of the founders of the Yugoslav Anthroposophical Society Marija Sofija, which is still active in Zagreb. From 1935, he had been collecting interesting exhibits for what was to become the core of the hospital museum. PMID- 22047486 TI - [Burn injuries: what have we learned from history]. AB - Severe burn injuries present a significant public health risk and are often associated with a life-threatening systemic inflammatory response. With the traditional approach, patients often stay in hospital longer and are more prone to problems like joint contractures, hypertrophic scars and infections due to delayed healing. The approach to burn injuries has been improving through and has been adopting new technologies and materials. Today, burn injuries are treated by general practitioners and surgeons. Unfortunately, this does not always ensure faster healing improvement of the quality of life. PMID- 22047487 TI - [The tragic demise of head physician Ortensio Pepi in Pula in 1938]. AB - The description represents a frame - an anecdotal one from today's perspective - from the history of surgery in Pula, to which the author's attention was directed by the late Vilijam Bilic, M.D., head of the Section for surgical diseases of the General Hospital in Pula. Head physician Ortensio Pepi, head of surgery of the then Regional Hospital, died in Pula on January 17, 1938 from gunshot wounds inflicted ten days before. He was shot in the street by a husband of a patient that died three months before following a difficult surgery. It appears that the gunman passed judgement on himself immediately after the insane act by shooting himself in the head, and died the same evening. The event garnered a lot of attention from the only newspaper of the time in Pula - Corriere Istriano, through which we keep track of the difficult, yet successful abdomen surgery and the gradual recovery of head physician Pepi. However, several days after the reporter published that the patient"s condition is no longer life threatening, Ortensio Pepi died "due to complications". PMID- 22047488 TI - Heart surgeon Miro Kosak (1919-2010) and his contribution to the development of cardiovascular surgery in slovenia. AB - Heart surgeon Miro Kosak was a pioneer of modern cardiovascular surgery in Slovenia; in 1958, he performed the first open-heart surgery with extracorporeal circulation, in 1965, the first implantation of heart valve and pacemaker, and in 1971, the first bypass on coronary arteries. He also paved the way for heart transplantations that followed. PMID- 22047489 TI - The cerebellum and neuropsychological functioning: a critical review. AB - The cerebellum, while once considered a brain region principally involved in motor control and coordination, is increasingly becoming associated with a range of neuropsychological and neuropsychiatric presentations. This paper reviews the dominant neuropsychological domains and neuropsychiatric conditions for which cerebellar involvement has been demonstrated, including visuospatial functioning, learning and memory, language, executive functioning, attention deficit/hyperactivity disorder, autism spectrum disorders, and schizophrenia. The paper concludes with a discussion of a potential neuropsychological localization model within the cerebellum and a discussion of prognosis and rates of recovery that can be expected, following localized cerebellar lesions. PMID- 22047490 TI - Study of probe-sample distance for biomedical spectra measurement. AB - BACKGROUND: Fiber-based optical spectroscopy has been widely used for biomedical applications. However, the effect of probe-sample distance on the collection efficiency has not been well investigated. METHOD: In this paper, we presented a theoretical model to maximize the illumination and collection efficiency in designing fiber optic probes for biomedical spectra measurement. This model was in general applicable to probes with single or multiple fibers at an arbitrary incident angle. In order to demonstrate the theory, a fluorescence spectrometer was used to measure the fluorescence of human finger skin at various probe-sample distances. The fluorescence spectrum and the total fluorescence intensity were recorded. RESULTS: The theoretical results show that for single fiber probes, contact measurement always provides the best results. While for multi-fiber probes, there is an optimal probe distance. When a 400- MUm excitation fiber is used to deliver the light to the skin and another six 400- MUm fibers surrounding the excitation fiber are used to collect the fluorescence signal, the experimental results show that human finger skin has very strong fluorescence between 475 nm and 700 nm under 450 nm excitation. The fluorescence intensity is heavily dependent on the probe-sample distance and there is an optimal probe distance. CONCLUSIONS: We investigated a number of probe-sample configurations and found that contact measurement could be the primary choice for single-fiber probes, but was very inefficient for multi-fiber probes. There was an optimal probe-sample distance for multi-fiber probes. By carefully choosing the probe sample distance, the collection efficiency could be enhanced by 5-10 times. Our experiments demonstrated that the experimental results of the probe-sample distance dependence of collection efficiency in multi-fiber probes were in general agreement with our theory. PMID- 22047491 TI - Management of asthma in pregnant women by general practitioners: a cross sectional survey. AB - BACKGROUND: Poorly controlled asthma can lead to maternal and fetal complications. Despite the known risks of poorly controlled asthma during pregnancy and the need for stepping up therapy when appropriate, there are concerns that management is suboptimal in primary care.Our objective was to investigate the management of asthma during pregnancy by general practitioners providing shared maternity care. METHODS: A pre-piloted, anonymous mail survey was sent to all general practitioners (n = 842) involved in shared maternity care at six maternity hospitals in Victoria, Australia. Respondents were asked about their perceived safety of individual asthma medications during pregnancy. Approach to asthma management during pregnancy was further explored using scenarios of pregnant women with stable and deteriorating asthma and poor medication adherence. RESULTS: Inhaled corticosteroids (ICS) were perceived to be the safest and were the preferred preventive medication in first trimester (74.1%), whilst leukotriene receptor antagonists were the least preferred (2.9%). A quarter (25.8%) of respondents would stop or decrease patients' ICS doses during pregnancy, even when their asthma was well controlled by current therapy. In addition, 12.1% of respondents were not sure how to manage deteriorating asthma during pregnancy and opted to refer to another health professional. Almost half the respondents (48.9%) reported encountering medication nonadherence during pregnancy. CONCLUSION: A lack of confidence and/or knowledge among general practitioners in managing deteriorating asthma in pregnancy was observed despite a good understanding of the safety of asthma medications during pregnancy, compliance with evidence-based guidelines in the selection of preventive medications, and self reported good asthma knowledge. PMID- 22047492 TI - Nanocapsules based on linear and Y-shaped 3-miktoarm star-block PEO-PCL copolymers as sustained delivery system for hydrophilic molecules. AB - Well-defined amphiphilic Y-shaped miktoarm star-block copolymers of PEO and PCL were synthesized by ring-opening polymerization of epsilon-caprolactone initiated by a PEO-bound lysine macroinitiator. The copolymers were characterized by (1)H NMR, SEC, DSC, and WAXD techniques. Separate PCL and PEO crystalline phases occur in melt-crystallized copolymers when their segmental lengths were comparable and the PCL content was <=80 wt %. Self-assembling of these copolymers in aqueous medium led to nanoaggregates with low critical aggregation concentration values (0.35 to 1.6 mg.L(-1)) and size depending on composition. Despite the fact that copolymers were not prone to self-organize in vesicles, once processed by a novel w/o emulsion-melting-sonication technique, they gave nanocapsules with a water core and a hydrophilic surface. A macromolecular fluorescent dye was effectively loaded and released at sustained rate by optimizing nanocapsule formulation. The results demonstrate that amphiphilic block copolymers can be assembled in different kinds of nanomorphologies independently of their hydrophilic/hydrophobic balance and architecture through specifically designed preparation techniques. PMID- 22047493 TI - Functional analysis of UGT1A4(P24T) and UGT1A4(L48V) variant enzymes. AB - AIM: To investigate the effects of two nonsynonymous SNPs, UGT1A4*2 (rs#: 6755571, 70C>A, P24T) and UGT1A4*3 (rs#: 2011425, 142T>G, L48V), on the function of UGT1A4 against dihydrotestosterone (DHT), transandrosterone (t-AND), lamotrigine (LTG) and tamoxifen (TAM). MATERIALS & METHODS: Detailed kinetic experiments were conducted with recombinant UGT1A4(wild-type), UGT1A4(P24T) and UGT1A4(L48V), which were overexpressed in HEK293 cell lines. The kinetic profiles and kinetic parameters (K(m), V(max) and CL(int)) obtained with either UGT1A4(P24T) or UGT1A4(L48V) were compared with those obtained with the wild-type enzyme. The interaction of TAM on UG1A4-catalyzed DHT glucuronidation was also investigated with the three UGT1A4 polymorphic enzymes. RESULTS: UGT1A4(L48V) had higher enzyme efficiency (CL(int)) compared with wild-type UGT1A4 on DHT glucuronidation; UGT1A4(P24T) and UGT1A4(L48V) had lower CL(int) than wild-type UGT1A4 for t-AND and LTG glucuronidation. The TAM CL(int) with UGT1A4(P24T) and UGT1A4(L48V) glucuronidation and the UGT1A4(P24T)-catalyzed DHT glucuronidation were, on the other hand, similar to those of the wild-type enzyme. With all three enzymes, TAM activated UGT1A4-catalyzed DHT glucuronidation in a concentration dependent fashion. CONCLUSION: Decreased CL(int) of UGT1A4(P24T) and UGT1A4(L48V) on LTG glucuronidation may lead to interindividual variations in LTG metabolism in vivo. However, it is less likely that these polymorphisms would have impact on DHT and t-AND metabolism in vivo because these compounds are glucuronidated by multiple enzymes. PMID- 22047494 TI - Editorial. PMID- 22047495 TI - Nicolaas Adriaan van der Velden (1927-1979). PMID- 22047496 TI - Investigation of protein conformational stability employing a multimodal spectrometer. AB - The conformational stability of proteins is typically investigated by use of a variety of biophysical measurements as a function of environmental stresses such as pH and temperature. Thus, multiple experiments are required on a variety of instruments, each providing information on a particular aspect of a protein's higher order structural integrity. These measurements typically require large sample quantities and long experimental times. In this study, a new methodology is described to obtain protein conformational stability data simultaneously, including UV absorption, light scattering, and near- and far-UV circular dichroism, by employing a multimodal spectrometer. Fluorescence spectral data are also collected on the same instrument, although not simultaneously. The method was developed by examining the thermal and pH stability of four model proteins. Results showed reproducible and accurate results from this single instrument, and data collection was rapid with minimal protein sample requirements. We illustrate the application of this method to the generation of empirical phase diagrams (EPDs) to better characterize the overall conformational stability of proteins. This new approach facilitates the rapid characterization of protein structure and stability in a single methodology, useful for analysis of unknown proteins as well as screening of solution conditions to optimize stability for protein therapeutic drug candidates. PMID- 22047498 TI - High prevalence of HPV in non-cervical sites of women with abnormal cervical cytology. AB - BACKGROUND: Human papillomaviruses (HPV) are causally associated with ano-genital and a subset of head and neck cancers. Rising incidence of HPV+ anal cancers and head and neck cancers have now been demonstrated in the developed world over the last decade. The majority of published data on HPV prevalence at the anal and oro pharyngeal sites are from studies of higher-risk populations. There is a paucity of data on the prevalence of HPV at non-cervical sites in lower risk, non-HIV+ women and this study was designed to provide initial pilot data on a population of women recalled for colposcopy as part of the UK cervical screening programme. METHODS: 100 non-HIV+ women with abnormal cervical cytology, attending clinic for colposcopic examination were recruited. Swabs from the oro-pharyngeal, anal and cervical sites were taken and DNA extracted. HPV detection and genotyping were performed using a standardised, commercially available PCR-line blot assay, which is used to genotype 37 HPV subtypes known to infect the ano-genital and oro pharyngeal areas. Strict sampling and laboratory precautions were taken to prevent cross-contamination. RESULTS: There was a very high prevalence of HPV infection at all three sites: 96.0%, 91.4% and 92.4% at the cervix, anus and oro pharynx, respectively. Multiple HPV subtype infections were dominant at all 3 mucosal sites. At least one or more HR genotype was present at both the cervix/anus in 39/52 (75.0%) patients; both the cervix/oro-pharynx in 48/56 (85.7%) patients; and both the anus/oro-pharynx in 39/52 (75.0%) patients. HPV 16 infection was highly dominant across all mucosal sites, with over a 2-fold increase over the next most prevalent subtype (HPV 31). CONCLUSIONS: Women with abnormal smears have widespread infection with high-risk HPV at the cervical, anal and oro-pharyngeal mucosal sites and may represent a higher risk population for HPV disease in the future. PMID- 22047499 TI - Bacteriophage lysis of Enterococcus host strains: a tool for microbial source tracking? AB - This paper describes the isolation of Enterococcus host strains, for potential use as simple bacteriophage (phage)-based microbial source tracking (MST) tools. Presumptive Enterococcus host strains were isolated from cattle feces, raw municipal wastewater, agricultural runoff, and waters impacted by farms or wastewater treatment works (WWTW) in southern England, United Kingdom (UK). All enterococcal host strains (n = 390) were first screened for their ability to detect phage in samples of raw municipal wastewater and fecal material from cattle, pigs, and sheep. Host strains that detected phage (n = 147) were ranked according to both their specificity to a particular fecal source and also the number of phages (expressed as plaque-forming units, PFU) that they detected per milliliter of sample. Host strains that demonstrated host specificity and which detected phages at levels greater than 100 PFU/mL (n = 29) were further tested using additional fecal samples of human and nonhuman origin. The specificity and sensitivity of the enterococcal host strains were found to vary, ranging from 44 to 100% and from 17 to 83%, respectively. Most notably, seven strains exhibited 100% specificity to either cattle, human, or pig samples. Isolates exhibiting specificity to cattle were identified as belonging to the species Enterococcus casseliflavus , Enterococcus mundtii , or Enterococcus gallinarum , while human and pig isolates were members of either Enterococcus faecium or Enterococcus faecalis . The high specificity of phages infecting Enterococcus hosts and the simplicity and relatively low cost of the approach collectively indicate a strong potential for using this method as a tool in MST. PMID- 22047500 TI - QTL detection for Aeromonas salmonicida resistance related traits in turbot (Scophthalmus maximus). AB - BACKGROUND: Interactions between fish and pathogens, that may be harmless under natural conditions, often result in serious diseases in aquaculture systems. This is especially important due to the fact that the strains used in aquaculture are derived from wild strains that may not have had enough time to adapt to new disease pressures. The turbot is one of the most promising European aquaculture species. Furunculosis, caused by the bacterium Aeromonas salmonicida, produces important losses to turbot industry. An appealing solution is to achieve more robust broodstock, which can prevent or diminish the devastating effects of epizooties. Genomics strategies have been developed in turbot to look for candidate genes for resistance to furunculosis and a genetic map with appropriate density to screen for genomic associations has been also constructed. In the present study, a genome scan for QTL affecting resistance and survival to A. salmonicida in four turbot families was carried out. The objectives were to identify consistent QTL using different statistical approaches (linear regression and maximum likelihood) and to locate the tightest associated markers for their application in genetic breeding strategies. RESULTS: Significant QTL for resistance were identified by the linear regression method in three linkage groups (LGs 4, 6 and 9) and for survival in two LGs (6 and 9). The maximum likelihood methodology identified QTL in three LGs (5, 6 and 9) for both traits. Significant association between disease traits and genotypes was detected for several markers, some of them explaining up to 17% of the phenotypic variance. We also identified candidate genes located in the detected QTL using data from previously mapped markers. CONCLUSIONS: Several regions controlling resistance to A. salmonicida in turbot have been detected. The observed concordance between different statistical methods at particular linkage groups gives consistency to our results. The detected associated markers could be useful for genetic breeding strategies. A finer mapping will be necessary at the detected QTL intervals to narrow associations and around the closely associated markers to look for candidate genes through comparative genomics or positional cloning strategies. The identification of associated variants at specific genes will be essential, together with the QTL associations detected in this study, for future marker assisted selection programs. PMID- 22047501 TI - Addressing the Grand Challenge of atmospheric carbon dioxide: geologic sequestration vs. biological recycling. AB - On February 15, 2008, the National Academy of Engineering unveiled their list of 14 Grand Challenges for Engineering. Building off of tremendous advancements in the past century, these challenges were selected for their role in assuring a sustainable existence for the rapidly increasing global community. It is no accident that the first five Challenges on the list involve the development of sustainable energy sources and management of environmental resources. While the focus of this review is to address the single Grand Challenge of "develop carbon sequestration methods", is will soon be clear that several other Challenges are intrinsically tied to it through the principles of sustainability. How does the realm of biological engineering play a role in addressing these Grand Challenges? PMID- 22047502 TI - Re-examination of the dimerization state of leucine-rich repeat kinase 2: predominance of the monomeric form. AB - Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene have been identified in PARK8, a major form of autosomal-dominantly inherited familial Parkinson's disease, although the biochemical properties of LRRK2 are not fully understood. It has been proposed that LRRK2 predominantly exists as a homodimer on the basis of the observation that LRRK2, with a theoretical molecular mass of 280 kDa, migrates at 600 kDa (p600 LRRK2) on native polyacrylamide gels. In the present study, we biochemically re-examined the nature of p600 LRRK2 and found that p600 LRRK2 was fractionated with a single peak at ~272 kDa by ultracentrifugation on a glycerol gradient. In addition, p600 LRRK2 behaved similarly to monomeric proteins upon two-dimensional electrophoretic separation. These results suggested a monomeric composition of p600 LRRK2 within cells. The p600 LRRK2 exhibited kinase activity as well as GTP-binding activity, and forced dimerization of LRRK2 neither upregulated its kinase activity nor altered its subcellular localization. Collectively, we conclude that the monomer form of LRRK2 is predominant within cells, and that dimerization is dispensable for its enzymatic activity. PMID- 22047503 TI - RNA interference-based resistance against a legume mastrevirus. AB - BACKGROUND: RNA interference (RNAi) is a homology-dependant gene silencing mechanism and has been widely used to engineer resistance in plants against RNA viruses. However, its usefulness in delivering resistance against plant DNA viruses belonging to family Geminiviridae is still being debated. Although the RNAi approach has been shown, using a transient assay, to be useful in countering monocotyledonous plant-infecting geminiviruses of the genus Mastrevirus, it has yet to be investigated as a means of delivering resistance to dicot-infecting mastreviruses. Chickpea chlorotic dwarf Pakistan virus (CpCDPKV) is a legume infecting mastrevirus that affects chickpea and other leguminous crops in Pakistan. RESULTS: Here a hairpin (hp)RNAi construct containing sequences encompassing part of replication-associated protein gene, intergenic region and part of the movement protein gene of CpCDPKV under the control of the Cauliflower mosaic virus 35S promoter has been produced and stably transformed into Nicotiana benthamiana. Plants harboring the hairpin construct were challenged with CpCDPKV. All non-transgenic N. benthamiana plants developed symptoms of CpCDPKV infection within two weeks post-inoculation. In contrast, none of the inoculated transgenic plants showed symptoms of infection and no viral DNA could be detected by Southern hybridization. A real-time quantitative PCR analysis identified very low level accumulation of viral DNA in the inoculated transgenic plants. CONCLUSIONS: The results presented show that the RNAi-based resistance strategy is useful in protecting plants from a dicot-infecting mastrevirus. The very low levels of virus detected in plant tissue of transgenic plants distal to the inoculation site suggest that virus movement and/or viral replication was impaired leading to plants that showed no discernible signs of virus infection. PMID- 22047504 TI - Palladium-catalyzed allylic substitution with (eta6-arene-CH2Z)Cr(CO)(3)-based nucleophiles. AB - Although the palladium-catalyzed Tsuji-Trost allylic substitution reaction has been intensively studied, there is a lack of general methods to employ simple benzylic nucleophiles. Such a method would facilitate access to "alpha-2-propenyl benzyl" motifs, which are common structural motifs in bioactive compounds and natural products. We report herein the palladium-catalyzed allylation reaction of toluene-derived pronucleophiles activated by tricarbonylchromium. A variety of cyclic and acyclic allylic electrophiles can be employed with in situ generated (eta(6)-C(6)H(5)CHLiR)Cr(CO)(3) nucleophiles. Catalyst identification was performed by high throughput experimentation (HTE) and led to the Xantphos/palladium hit, which proved to be a general catalyst for this class of reactions. In addition to eta(6)-toluene complexes, benzyl amine and ether derivatives (eta(6)-C(6)H(5)CH(2)Z)Cr(CO)(3) (Z = NR(2), OR) are also viable pronucleophiles, allowing C-C bond-formation alpha to heteroatoms with excellent yields. Finally, a tandem allylic substitution/demetalation procedure is described that affords the corresponding metal-free allylic substitution products. This method will be a valuable complement to the existing arsenal of nucleophiles with applications in allylic substitution reactions. PMID- 22047505 TI - Public perspectives about pharmacogenetic testing and managing ancillary findings. AB - AIMS: Pharmacogenetic (PGx) tests are intended to improve therapeutic outcomes through predicting a patient's likelihood to respond to or experience an adverse effect from a specific treatment. In addition, PGx testing may also generate ancillary, or incidental, disease information unrelated to the purpose for which the test was ordered. To assess public attitudes toward PGx testing, ancillary disease risk information and related clinical issues, we conducted a series of focus groups. RESULTS: Forty-five individuals recruited from Durham, NC, participated in four focus groups. Overall, participants were enthusiastic about PGx testing, though expressed concerns about privacy, confidentiality, and psychological harms associated with ancillary information. Focus group participants believed that physicians had a responsibility to disclose ancillary risk information, but were concerned about managing and coping with unexpected disease risk information. CONCLUSION: We find that participants welcomed the integration of PGx testing into therapeutic decision-making. Public concerns about PGx testing and ancillary information specifically centered on personal implications of learning such additional information, suggesting that patient provider discussion of the benefits and risks of testing will be necessary until public familiarity with these tests increases. PMID- 22047506 TI - Association of CD36 gene variants and metabolic syndrome in Iranians. AB - AIMS: The CD36 gene encodes for a membrane receptor that facilitates fatty-acid uptake and utilization. Genetic variants of the CD36 gene have been associated with metabolic syndrome (MetS). We aimed to evaluate the association between the rs10499859A>G and rs13246513C>T polymorphisms and MetS components. METHODS: For this case-control study, 140 MetS and 187 normal subjects were randomly selected from the Tehran Lipid and Glucose Study participants. Biochemical and anthropometrical variables were measured. Genotyping for both single nucleotide polymorphisms (SNPs) was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Case and control groups were not different in allele and genotype frequencies for these SNPs. However, the A and T alleles of these SNPs were significantly associated with elevated levels of high-density lipoprotein cholesterol (HDL-C) before age and sex adjustment (p=0.027 and 0.016, respectively). Association between the A allele and body mass index (BMI) was also significant after adjustment for MetS under the dominant model (p=0.009, beta(2)=0.68). CONCLUSIONS: Based on our results, these polymorphisms do affect HDL-C level and BMI (MetS components), although the effect may be slight and restricted specifically to an environment-genotype. PMID- 22047507 TI - Recurrent pregnancy loss and its relation to combined parental thrombophilic gene mutations. AB - BACKGROUND AND AIM: Recurrent pregnancy loss (RPL) is a heterogeneous disorder that has been associated with antiphospholipid syndrome and other prothrombotic parameters. We aimed to investigate the prevalence of 12 thrombophilic gene mutations in RPL couples in the current results. METHOD: In a total of 543 Turkish women with RPL and 327 of their male partners (870 individuals with RPL), and a control group of 106 fertile couples (control) were analyzed for factor V leiden (FVL), factor V H1299R, factor II prothrombin G20210A, FXIII V34L, beta fibrinogen -455G>A, plasminogen activator inhibitor-1 (PAI-1), GPIIIa L33P (HPA-1 a/b L33P), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q, and Apo E genes. RESULTS: The overall, heterozygous and/or homozygous point mutations in FVL-FVR2, ApoE2, PAI-1, MTHFR C677T-A1298C, and ACE genes were associated with RPL. There was no meaningful association between RPL and other studied genes. CONCLUSION: The homozygosity of 4G in PAI-1 and MTHFR C677T genes in women with RPL, and heterozygosity of FVL, FVR2, ACE, and ApoE2 genes in both parents play crucial role in RPL and should be considered as a risk factor in RPL. Current results showed that RPL is related to combined parental (not only maternal) thrombophilic gene mutations. PMID- 22047508 TI - Does quality of care for hypertension in primary care vary with postcode area deprivation? An observational study. AB - BACKGROUND: Hypertension is a common major risk factor for stroke and coronary heart disease. Little is known about how achievement of financially incentivised and non-incentivised indicators of quality of care varies with deprivation, or about the effect of financial incentives on health inequalities in hypertension. General practices in the UK have received financial incentives for high quality care since 2004. This study set out to assess the variations in achievement of incentivised and non-incentivised quality indicators for hypertension by patient area deprivation, before and after the introduction of financial incentives. METHODS: Achievement of 14 quality indicators for hypertension in 304 patient participants in 18 general practices in Norfolk, England was assessed one year before (2003) and one year after (2005) the introduction of financial incentives. Four indicators were incentivised and 10 were non-incentivised. Each participant's postcode was linked to an index of multiple deprivation score. RESULTS: The range of achievement of incentivised quality indicators was 65-94% in the least deprived third of participants, and 77-94% in the most deprived third in 2003 and 2005 combined. For non-incentivised indicators, the range was 7 85% in the least deprived and 24-93% in the most deprived third.Achievement of incentivised quality indicators in 2003 and 2005 combined did not vary significantly by area deprivation. Achievement of three of 10 non-incentivised indicators was higher in participants from more deprived postcode areas: providing lifestyle advice (odds ratio 1.34, 95% confidence interval 1.00-1.79), assessment of peripheral vascular disease (1.54, 1.02-2.35) and electrocardiography (1.38, 1.04-1.82). CONCLUSIONS: Participants from more deprived areas received at least the same, and sometimes better, quality of care than those from less deprived areas. Quality of care for hypertension in general practice may not follow the inequitable distribution seen with some other conditions. PMID- 22047511 TI - ERRATUM. PMID- 22047509 TI - Role of MetMAb (OA-5D5) in c-MET active lung malignancies. AB - INTRODUCTION: MetMAb (OA-5D5) is a one-armed monoclonal antibody developed to bind to and inhibit c-MET receptor tyrosine kinase. Though only in early clinical testing, this agent holds great promise in diseases thought to be driven by c-MET activation, as evidenced by the Phase II results in NSCLC where a benefit in overall survival was observed in patients with MET-diagnostic-positive disease. Thus far, both alone and in combination with other targeted agents, this drug has been well tolerated and no new significant safety signals have been identified. AREAS COVERED: This review summarizes the structure and function of the c-MET receptor and its ligand hepatic growth factor (HGF), provides an overview of select targeted monotherapies developed to interfere in the MET-HGF signaling pathway, discusses pre-clinical and clinical data surrounding MetMAb, and concludes with an expert opinion regarding this novel agent. EXPERT OPINION: MetMAb has been well tolerated and based on Phase II data testing it, in combination with erlotinib in advanced NSCLC, may have a role in improving survival in patients with disease driven by c-MET activation. However, Phase III validation is underway and the results of these studies will help elucidate which patients will benefit most from this novel agent. PMID- 22047516 TI - Interaction of biological molecules with clay minerals: a combined spectroscopic and sorption study of lysozyme on saponite. AB - The interaction of hen egg white lysozyme (HEWL) with Na- and Cs-exchanged saponite was investigated using sorption, structural, and spectroscopic methods as a model system to study clay-protein interactions. HEWL sorption to Na- and Cs saponite was determined using the bicinchoninic acid (BCA) assay, thermogravimetric analysis, and C and N analysis. For Na-saponite, the TGA and elemental analysis-derived sorption maximum was 600 mg/g corresponding to a surface coverage of 0.85 ng/mm(2) with HEWL occupying 526 m(2)/g based on a cross sectional area of 13.5 nm(2)/molecule. HEWL sorption on Na-saponite was accompanied by the release of 9.5 Na(+) ions for every molecule of HEWL sorbed consistent with an ion exchange mechanism between the positively charged HEWL (IEP 11) and the negatively charged saponite surface. The d-spacing of the HEWL Na-saponite complex increased to a value of 4.4 nm consistent with the crystallographic dimensions of HEWL of 3 * 3 * 4.5 nm. In the case of Cs saponite, there was no evidence of interlayer sorption; however, sorption of HEWL to the "external" surface of Cs-saponite showed a high affinity isotherm. FTIR and Raman analysis of the amide I region of the HEWL-saponite films prepared from water and D(2)O showed little perturbation to the secondary structure of the protein. The overall hydrophilic nature of the HEWL-Na-saponite complex was determined by water vapor sorption measurements. The clay retained its hydrophilic character with a water content of 18% at high humidity corresponding to 240 H(2)O molecules per molecule of HEWL. PMID- 22047517 TI - Geographic variation in physicians' responses to a reimbursement change. PMID- 22047518 TI - Evidence-based medicine in the EMR era. PMID- 22047519 TI - The prevalence of undiagnosed chronic obstructive pulmonary disease in a primary care population with respiratory tract infections - a case finding study. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an underdiagnosed cause of morbidity and mortality worldwide. Prevalence of COPD has been shown to be highly associated with positive smoking history and increasing age. Spirometry is the method used for diagnosing COPD. However, identifying patients at risk of COPD to undergo spirometry tests has been challenging. Therefore, there is a need for new cost-effective and feasible diagnostic screening procedures for use in primary care centers. Our aim was to describe the prevalence and severity of undiagnosed COPD in a group of patients with respiratory infections attending urgent primary care, and to identify those variables in patients' history that could be used to detect the disease. METHODS: Patients of 40-75 years (n = 138) attending urgent primary care center with acute respiratory tract infection, positive smoking history and no previously known pulmonary disease underwent pre- and post bronchodilator spirometry testing four to five weeks after the acute infection. Prevalence and severity of COPD were estimated following the Global Initiative for COPD (GOLD) criteria. Variables such as sex, age, current smoking status, smoking intensity (pack years) and type of infection diagnosis were assessed for possible associations with COPD. RESULTS: The prevalence of previously undiagnosed COPD in our study group was 27%, of which 45% were in stage 1 (FEV1 >= 80% of predicted), 53% in stage 2 (50 <= FEV1 < 80% of predicted), 3% in stage 3 (30 <= FEV1 < 50% of predicted) and 0% in stage 4 (FEV1 < 30% of predicted). We found a significant association between COPD and age >= 55 (OR = 10.9 [95% CI 3.8-30.1]) and between COPD and smoking intensity (pack years > 20) (OR = 3.2 [95% CI 1.2-8.5]). Sex, current smoking status and type of infection diagnosis were not shown to be significantly associated with COPD. CONCLUSION: A middle-aged or older patient with any type of common respiratory tract infection, positive smoking history and no previously known pulmonary disease has an increased likelihood of having underlying COPD. These patients should be offered spirometry testing for diagnosis of COPD. PMID- 22047520 TI - Positive association of the hepatic lipase gene polymorphism c.514C > T with estrogen replacement therapy response. AB - BACKGROUND: Hepatic lipase (HL), an enzyme present in the hepatic sinusoids, is responsible for the lipolysis of lipoproteins. Human HL contains four polymorphic sites: G-250A, T-710C, A-763G, and C-514T single-nucleotide polymorphism (SNPs). The last polymorphism is the focus of the current study. The genotypes associated with the C-514T polymorphism are CC (normal homozygous - W), CT (heterozygous - H), and TT (minor-allele homozygous - M). HL activity is significantly impaired in individuals of the TT and CT genotypes. A total of 58 post-menopausal women were studied. The subjects were hysterectomized women receiving hormone replacement therapy consisting of 0.625 mg of conjugated equine estrogen once a day. The inclusion criteria were menopause of up to three years and normal blood tests, radiographs, cervical-vaginal cytology, and densitometry. DNA was extracted from the buccal and blood cells of all 58 patients using a commercially available kit (GFX(r) - Amersham-Pharmacia, USA). RESULTS: Statistically significant reductions in triglycerides (t = 2.16; n = 58; p = 0.03) but not in total cholesterol (t = 0.14; n = 58; p = 0.89) were found after treatment. This group of good responders were carriers of the T allele; the CT and TT genotypes were present significantly more frequently than in the group of non-responders (p = 0.02 or p = 0.07, respectively). However, no significant difference in HDL-C (t = 0.94; n = 58; p = 0.35) or LDL-C (t = -0.83; n = 58; p = 0.41) was found in these patients. CONCLUSIONS: The variation in lipid profile associated with the C 514T polymorphism is significant, and the T allele is associated with the best response to ERT. PMID- 22047525 TI - Association between nitric oxide and 8-hydroxydeoxyguanosine levels in semen of diabetic men. AB - The incidence of diabetes mellitus is rapidly increasing in the world. One of the complications of diabetes includes disturbance of the reproductive tract, such as infertility, erectile dysfunction, and endocrine disruption. Nitric oxide (NO) is a free radical produced by most cells including the human male and female reproductive tracts. NO has a dual role where low concentrations are essential for homeostatic cellular biology and physiology, but high levels have detrimental effects relating to cellular damage from this reactive oxygen species (ROS). 8 hydroxydeoxyguanosine (8-OHdG) is an oxidized nucleoside of DNA that is currently used as a biomarker of cellular oxidative stress, where urinary levels can correlate with diabetic nephropathy and retinopathy. Our aim was to investigate the relationship between nitrate/nitrite levels and 8-OHdG levels in the semen of diabetic and non-diabetic men. Concentrations of nitrate/nitrite and 8-OHdG were examined in seminal plasma of 32 diabetic and 35 non-diabetic men. The level of nitrate/nitrite was assayed by colorimetric reaction and 8-OHdG was measured by ELISA. Our results showed that the seminal plasma nitrate/nitrite levels were significantly higher in the diabetic group (p < 0. 01). There were also significantly higher 8-OHdG levels in diabetic men compared to non-diabetic men (p < 0.05). Regression analysis indicated that in diabetic men, nitrate/nitrite levels correlated well with 8-OHdG levels (r = 0.64, p < 0.001). A significant trend between nitrate/nitrite and sperm parameters was not observed. Our data suggests that high levels of nitrate/nitrite in the semen of diabetic men is suggestive of reactive oxygen species induced DNA damage that is correlated with 8-OHdG levels but not sperm parameters. These results support the further investigation of NO and 8-OHdG as biomarkers for assessing male infertility. PMID- 22047526 TI - Editorial. PMID- 22047528 TI - Advancements in top-down proteomics. PMID- 22047529 TI - Association between the results of the childhood asthma control test and objective parameters in asthmatic children. AB - OBJECTIVE: The Childhood Asthma Control Test (C-ACT), a seven-item, self administered questionnaire, has been used as a tool to assess the control level in children with asthma. The aim of this study was to determine whether the C-ACT reflects airflow limitation and airway inflammation in addition to clinical manifestations. METHODS: Asthmatic children aged 5-11 years who were able to perform the lung function test and fractional exhaled nitric oxide (FeNO) evaluation correctly were recruited during their regular visits. Children and their parents were asked to answer the officially developed Japanese version of the C-ACT. RESULTS: Among 258 children (176 boys, median age 9 years), there was a significant positive correlation between the C-ACT score and the percent predicted forced expiratory volume in 1 s (%FEV(1)) (r = 0.317, p < .001). The accuracy of the C-ACT for identifying asthmatic subjects with normal lung function (%FEV(1) >80%) described as the area under the receiver operating characteristic curve was 71.5% (95% CI = 62.8-80.2%, p < .001), and based on the Youden index the optimal cutoff score was 23 (sensitivity of 78% and specificity of 54%). In contrast, there was no relationship between the C-ACT score and the FeNO value. CONCLUSIONS: These results suggest that a cutoff score of 23 for the C-ACT could be useful for identifying children with well-controlled asthma and normal lung function. Further studies are warranted to develop an easy-to-use questionnaire to assess the extent of airway inflammation in children. PMID- 22047530 TI - Cationic liposome-mediated CXCR4 gene delivery into hematopoietic stem/progenitor cells: implications for clinical transplantation and gene therapy. AB - The chemokine stromal cell-derived factor (SDF)-1alpha/CXCL12 and its receptor CXC chemokine receptor 4 (CXCR4) play a crucial role in the homing/engraftment and retention of hematopoietic stem/progenitor cells (HSPCs) in the bone marrow. It has been shown using the viral gene transfer technique that CXCR4 overexpression on human CD34(+) HSPC significantly improves their engraftment in murine models. However, clinical trials with gene therapy have revealed safety concerns related to the immunogenicity of the viral carriers, due to the random integration of viral genes into the host genome. Therefore, a method for CXCR4 gene delivery into HSPC that is safe, nonviral, and highly efficient is needed to improve clinical transplantation and gene therapies. In this work, we investigated the nonviral CXCR4 gene delivery into HSPC using the cationic liposome agent IBAfect. We used CD34(+) cells from cord blood and the models of immature hematopoietic cells expressing CD34 antigen, namely, leukemic cell lines KG-1a and KG-1. Transfection efficiency was determined by flow cytometric analysis 12, 24, 48, and 72 h after transfection, and the viability of cells analyzed by trypan blue exclusion and MTS assays. The functional response of CXCR4-transfected HSPC toward an SDF-1alpha gradient was determined by chemotaxis assay. We found that ~25% transfection is achieved for KG-1a and KG-1 cells and 20% for HSPC, and that the viability of CXCR4-transfected HSPC is not significantly altered. More importantly, overexpression of CXCR4 using IBAfect significantly increased the chemotaxis of KG-1 cells and HSPC toward SDF-1alpha. However, we tested 2 other commercially available cationic liposomes (Lipofectamine 2000 and 1,2-dioleoyl-3-trimethylammonium-propane [DOTAP]) in parallel, and we found that they failed to deliver the CXCR4 gene into cells under the same conditions. These results suggest that IBAfect-mediated in vitro gene delivery to overexpress CXCR4 on HSPC is a safe and efficient technique with great potential for improving the efficacy of HSPC transplantation and gene therapy protocols. PMID- 22047531 TI - MicroRNA profiling of diverse endothelial cell types. AB - BACKGROUND: MicroRNAs are ~22-nt long regulatory RNAs that serve as critical modulators of post-transcriptional gene regulation. The diversity of miRNAs in endothelial cells (ECs) and the relationship of this diversity to epithelial and hematologic cells is unknown. We investigated the baseline miRNA signature of human ECs cultured from the aorta (HAEC), coronary artery (HCEC), umbilical vein (HUVEC), pulmonary artery (HPAEC), pulmonary microvasculature (HPMVEC), dermal microvasculature (HDMVEC), and brain microvasculature (HBMVEC) to understand the diversity of miRNA expression in ECs. RESULTS: We identified 166 expressed miRNAs, of which 3 miRNAs (miR-99b, miR-20b and let-7b) differed significantly between EC types and predicted EC clustering. We confirmed the significance of these miRNAs by RT-PCR analysis and in a second data set by Sylamer analysis. We found wide diversity of miRNAs between endothelial, epithelial and hematologic cells with 99 miRNAs shared across cell types and 31 miRNAs unique to ECs. We show polycistronic miRNA chromosomal clusters have common expression levels within a given cell type. CONCLUSIONS: EC miRNA expression levels are generally consistent across EC types. Three microRNAs were variable within the dataset indicating potential regulatory changes that could impact on EC phenotypic differences. MiRNA expression in endothelial, epithelial and hematologic cells differentiate these cell types. This data establishes a valuable resource characterizing the diverse miRNA signature of ECs. PMID- 22047532 TI - Antioxidant activity of seagrasses of the Mandapam coast, India. AB - CONTEXT: In the search for new sources of safe and inexpensive antioxidants, the leaves of eight species of seagrasses were screened for antioxidant properties. OBJECTIVE: Most of the seagrasses were evaluated for the first time for their antioxidant activities. MATERIALS AND METHODS: Total phenolic content and in vitro antioxidant activity using, 2,2-diphenyl-1-picrylhydrozyl (DPPH) radical scavenging capacity and FRAP assay. RESULTS: The leaves of Halophila stipulacea (Forssk.) Aschers showed high levels of phenols (1.398 +/- 0.055 mg GAE/g) and high reducing power (46.289 +/- 1.002) in terms of mg GAE/g. Similarly, H. pinifolia exhibited high total antioxidant activity (132.38, 75.027 mg AscAE/g) and a high percentage of DPPH radical scavenging activity (68.14%). The TAA and FRAP assays showed positive and significantly high correlation (R2 = 0.646). The total phenolic content in the seagrass extracts showed a better correlation with reducing power (R2 = 0.597) than the DPPH radical-scavenging activity (R2 = 0.495). DISCUSSION AND CONCLUSIONS: The antioxidant capacities of the seagrasses showed potential rich sources of natural antioxidants. Further studies are necessary for isolation and characterization of the active antioxidant compounds, which can be used to treat various oxidative stress-related diseases. PMID- 22047533 TI - Impact of the use of cryobank samples in a selected cattle breed: a simulation study. AB - BACKGROUND: High selection pressure on domestic cattle has led to an undesirable increase in inbreeding, as well as to the deterioration of some functional traits which are indirectly selected. Semen stored in a cryobank may be a useful way to redirect selection or limit the loss of genetic diversity in a selected breed. The purpose of this study was to analyse the efficiency of current cryobank sampling methods, by investigating the benefits of using cryopreserved semen in a selection scheme several generations after the semen was collected. METHODS: The theoretical impact of using cryopreserved semen in a selection scheme of a dairy cattle breed was investigated by simulating various scenarios involving two negatively correlated traits and a change in genetic variability of the breed. RESULTS: Our results indicate that using cryopreserved semen to redirect selection will have an impact on negatively selected traits only if it is combined with major changes in selection objectives or practices. If the purpose is to increase genetic diversity in the breed, it can be a viable option. CONCLUSIONS: Using cryopreserved semen to redirect selection or to improve genetic diversity should be carried out with caution, by considering the pros and cons of prospective changes in genetic diversity and the value of the selected traits. However, the use of genomic information should lead to more interesting perspectives to choose which animals to store in a cryobank and to increase the value of cryobank collections for selected breeds. PMID- 22047535 TI - Identifying and prioritizing strategies for comprehensive liver cancer control in Asia. AB - BACKGROUND: Liver cancer is both common and burdensome in Asia. Effective liver cancer control, however, is hindered by a complex etiology and a lack of coordination across clinical disciplines. We sought to identify strategies for inclusion in a comprehensive liver cancer control for Asia and to compare qualitative and quantitative methods for prioritization. METHODS: Qualitative interviews (N = 20) with international liver cancer experts were used to identify strategies using Interpretative Phenomenological Analysis and to formulate an initial prioritization through frequency analysis. Conjoint analysis, a quantitative stated-preference method, was then applied among Asian liver cancer experts (N = 20) who completed 12 choice tasks that divided these strategies into two mutually exclusive and exhaustive subsets. Respondents' preferred plan was the primary outcome in a choice model, estimated using ordinary least squares (OLS) and logistic regression. Priorities were then compared using Spearman's Rho. RESULTS: Eleven strategies were identified: Access to treatments; Centers of excellence; Clinical education; Measuring social burden; Monitoring of at-risk populations; Multidisciplinary management; National guidelines; Public awareness; Research infrastructure; Risk-assessment and referral; and Transplantation infrastructure. Qualitative frequency analysis indicated that Risk-assessment and referral (85%), National guidelines (80%) and Monitoring of at-risk populations (80%) received the highest priority, while conjoint analysis pointed to Monitoring of at-risk populations (p < 0.001), Centers of excellence (p = 0.002), and Access to treatments (p = 0.004) as priorities, while Risk-assessment and referral was the lowest priority (p = 0.645). We find moderate concordance between the qualitative and quantitative methods (rho = 0.20), albeit insignificant (p = 0.554), and a strong concordance between the OLS and logistic regressions (rho = 0.979; p < 0.0001). CONCLUSIONS: Identified strategies can be conceptualized as the ABCs of comprehensive liver cancer control as they focus on Antecedents, Better care and Connections within a national strategy. Some concordance was found between the qualitative and quantitative methods (e.g. Monitoring of at-risk populations), but substantial differences were also identified (e.g. qualitative methods gave highest priority to risk-assessment and referral, but it was the lowest for the quantitative methods), which may be attributed to differences between the methods and study populations, and potential framing effects in choice tasks. Continued research will provide more generalizable estimates of priorities and account for variation across stakeholders and countries. PMID- 22047536 TI - Synthesis and spectroscopic analysis of a stereoisomer library of the phytophthora mating hormone alpha1 and derived bis-Mosher esters. AB - Fluorous mixture synthesis provided all eight diastereomers of the phytophthora hormone alpha1 with the R configuration at C11 as individual samples after demixing and detagging. The library of all possible bis-Mosher esters (16) was then made by esterification. Complete sets of (1)H, (13)C, and (for the Mosher esters) (19)F NMR spectra were recorded, assigned, and compared with each other and with published spectra. Not all of the spectra are unique, and the (1)H NMR spectra of the Mosher esters provided the most information. The previous assignment of the natural sample as an "all-R" stereoisomer mixed with its 3S epimer was confirmed. PMID- 22047537 TI - Associations between levels of serum perfluorinated chemicals and adiponectin in a young hypertension cohort in Taiwan. AB - In animals, perfluorinated chemicals (PFCs), specifically perfluorooctanoic acid (PFOA) and perfluorooctane sulfate (PFOS), function as peroxisome proliferator activated receptor (PPAR) alpha agonists. However, the relevance of animal (primarily rodent) data to humans is unresolved. While plasma adiponectin level is very responsive to PPAR gamma agonist drugs, it has not been determined whether adiponectin level is related to serum PFCs concentrations. In the present study, 287 subjects (12-30 years of age) were recruited to determine the relationship between serum level of PFCs and serum level of adiponectin. The results showed males had higher serum PFOS concentrations than females and that those with metabolic syndrome had lower serum PFOA than controls. Besides, it showed regional elevations of the perfluoroundecanoic acid (PFUA) (median concentration: 7.11 ng/mL) in the study subjects. No relationship of PFOA, PFOS, PFUA, and the sum of all four PFCs was found to glucose homeostasis, adiponectin level, lipid profile, and inflammatory markers. The median and the range of perfluorononanoic acid (PFNA) concentration (in ng/mL; for four categories corresponding to the <50, 50-74, 75-89, and >=90th percentiles) were 0.38 (0.38 1.68), 3.22 (1.73-4.65), 5.85 (4.75-8.29), 10.56 (8.40-25.40), respectively. After controlling for confounding factors, multiple linear regression analysis revealed that the mean natural log-transformed level of adiponectin increased significantly across categories of PFNA (in ng/mL; 8.78, 8.73, 9.06, 9.36; P for trend = 0.010 in the full model). In conclusion, higher serum PFNA concentration is associated with elevated serum adiponectin concentration. PMID- 22047541 TI - Characteristics of epstein barr virus variants associated with gastric carcinoma in Southern Tunisia. AB - BACKGROUND: EBV-associated Gastric Carcinoma (EBVaGC) has a distinct clinical features and its prevalence is variable worldwide. RESULTS: To determine the prevalence of EBVaGC in Tunisia, EBV-encoded small RNA (EBER) expression was assessed in 81 gastric carcinoma (GC) specimens. The nuclear EBER expression was detected in 12 out of 81 GC cases (14.81%) and concordance between the score range of EBER staining and the number of EBV DNA copies as estimate by QPCR is observed. On the other hand, we found that EBVaGC strongly correlated with age at diagnosis, and weakly with tumor differentiation and venous invasion.Furthermore, the EBVaGC specimens were subjected to determine the EBV DNA polymorphisms. Our results show a unique genetic profile of the EBV strains regarding the A and D types, the F prototype, the retention of XhoI restriction site and the 30 bp del LMP1 variant. According to our previous studies on nasopharyngeal carcinoma (NPC), we suggested that EBV strains associated to GC and NPC shared some similarities in Tunisian patients. CONCLUSION: The prevalence of EBVaGC is of 14.81% in the southern Tunisia and that common EBV strain are associated with both NPC and GC which are likely to differ from Asian strains. Our findings support therefore a certain geographical distribution of EBV strains which is not restricted to EBV-associated malignancies. PMID- 22047543 TI - Nonparametric combinatorial sequence models. AB - This work considers biological sequences that exhibit combinatorial structures in their composition: groups of positions of the aligned sequences are "linked" and covary as one unit across sequences. If multiple such groups exist, complex interactions can emerge between them. Sequences of this kind arise frequently in biology but methodologies for analyzing them are still being developed. This article presents a nonparametric prior on sequences which allows combinatorial structures to emerge and which induces a posterior distribution over factorized sequence representations. We carry out experiments on three biological sequence families which indicate that combinatorial structures are indeed present and that combinatorial sequence models can more succinctly describe them than simpler mixture models. We conclude with an application to MHC binding prediction which highlights the utility of the posterior distribution over sequence representations induced by the prior. By integrating out the posterior, our method compares favorably to leading binding predictors. PMID- 22047542 TI - The VICI-trial: high frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: an international multicentre randomized controlled trial. AB - BACKGROUND: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly of the diaphragm resulting in pulmonary hypoplasia and pulmonary hypertension. It is associated with a high risk of mortality and pulmonary morbidity. Previous retrospective studies have reported high frequency oscillatory ventilation (HFO) to reduce pulmonary morbidity in infants with CDH, while others indicated HFO to be associated with worse outcome. We therefore aimed to develop a randomized controlled trial to compare initial ventilatory treatment with high-frequency oscillation and conventional ventilation in infants with CDH. METHODS/DESIGN: This trial is designed as a multicentre trial in which 400 infants (200 in each arm) will be included. Primary outcome measures are BPD, described as oxygen dependency by day 28 according to the definition of Jobe and Bancalari, and/or mortality by day 28. All liveborn infants with CDH born at a gestational age of over 34 weeks and no other severe congenital anomalies are eligible for inclusion. Parental informed consent is asked antenatally and the allocated ventilation mode starts within two hours after birth. Laboratory samples of blood, urine and tracheal aspirate are taken at the first day of life, day 3, day 7, day 14 and day 28 to evaluate laboratory markers for ventilator-induced lung injury and pulmonary hypertension. DISCUSSION: To date, randomized clinical trials are lacking in the field of CDH. The VICI-trial, as the first randomized clinical trial in the field of CDH, may provide further insight in ventilation strategies in CDH patient. This may hopefully prevent mortality and morbidity. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR1310. PMID- 22047544 TI - The necessity for the coating of perfluorodecalin-filled poly(lactide-co glycolide) microcapsules in the presence of physiological cholate concentrations: Tetronic-908 as an exemplary polymeric surfactant. AB - Recently, we demonstrated that biodegradable poly(lactide-co-glycolide) (PLGA) micro- and nanocapsules with a liquid content of perfluorodecalin are principally useful for the development of artificial oxygen carriers. In order to solve a decisive and well-known problem with PLGA microcapsules, i.e. the spontaneous agglomeration of the capsules after depletion of the emulsifying agent (i.e. cholate), coating with the ABA block copolymer, Tetronic-908 was studied. After Tetronic-908 treatment at concentrations that were harmless to cultured cells, the clustering of the microcapsules was prevented, the adsorption of opsonins was decreased and the attachment to cells was inhibited, but the oxygen transport capacity of PLGA microcapsules was even increased. The present data clearly show that perfluorodecalin-filled PLGA microcapsules must be coated before decreasing the emulsifying agent cholate to physiological concentrations, in order to develop a solution that has the capabilities to function as a potential artificial oxygen carrier suspension. PMID- 22047545 TI - Microencapsulation using vibrating technology. AB - For over a half a century now, microencapsulation has played a very important role in many industries and in the recent decades, this versatile technology has been applied to numerous biotechnology and medical processes. However, successful application in these areas requires a methodology which has the capability to produce mono-dispersed, homogenous-shaped capsules, with a narrow size distribution, using a short production time. The manufacture of capsules using vibrating technology has gained significant interest mainly due to its simplistic approach to produce homogenous microcapsules with the desired characteristics for biotechnological and medical processes. However, certain limitations still exist for this methodology, which include the inability to manufacture microcapsules at large quantities and/or using highly viscous polymers. In this review, a detailed description of the theoretical and practical aspects behind the production of different types of alginate-based microcapsules, for application in biotechnological and medical processes, using vibrating technology, is given. PMID- 22047546 TI - Formulation, optimization and evaluation of spray-dried mucoadhesive microspheres as intranasal carriers for Valsartan. AB - This investigation deals with the intranasal delivery of Valsartan, encapsulated in HPMC-based spray-dried mucoadhesive microspheres, with an aim to provide rapid absorption and quick onset of action for treating hypertension. A 23-factorial design has been employed for the assessment of influence of three independent variables, namely inlet temperature, feed-flow rate and drug-polymer ratio on production yield, particle size and in vitro drug diffusion of the prepared microspheres. Microspheres were evaluated for particle size, entrapment efficiency, swelling property, in vitro mucoadhesion, in vitro drug diffusion, ex vivo drug permeation, histopathological examination and stability studies. The results of differential scanning calorimetry, X-ray diffraction and scanning electron microscopy revealed molecular dispersion of Valsartan into microspheres with spherical shape and smooth surface. Optimized formulation indicated good mucoadhesion with no severe sign of damage on nasal mucosa. Results of the non invasive animal studies in dexamethasone-induced hypertensive rat model suggested the suitability of investigated drug delivery system for intranasal administration. PMID- 22047547 TI - PEGylated estradiol benzoate liposomes as a potential local vascular delivery system for treatment of restenosis. AB - This study was directed towards the preparation and optimization of PEGylated (PEG, poly(ethylene glycol)) estradiol benzoate (ESB)-loaded liposomes to be used for the treatment of restenosis by local vascular delivery. Various liposomal formulations were prepared by thin film hydration method followed by sonication. Response surface methodology was applied to study the influence of three different independent variables, on the response of entrapment efficiency (%EE). Liposomes were characterized in terms of size, zeta potential, %EE and release profile. Incorporation of ESB was higher in egg phosphatidylcholine (EPC) liposomes, whereas the drug was displaced from liposomes, as the cholesterol (Chol) content of liposome increased. The optimum formulation composed of EPC/dioleyloxy trimethylammonium propane/distearoylphosphatidylethanolamine PEG2000 with a molar proportion of 8.5:1:0.5 had the highest EE. In vivo studies in the balloon-injured rat carotid arteries revealed the potential of ESB-loaded liposomes as efficient local and controlled drug delivery systems to reduce restenosis. PMID- 22047548 TI - Mixture designs in the optimisation of PLGA nanoparticles: influence of organic phase composition on beta-aescin encapsulation. AB - The objective of this study was to enhance the encapsulation of the antileishmanial saponin aescin in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). We prepared the NPs by the O/W and W/O/W combined emulsification solvent evaporation/salting-out technique and investigated the influence of organic phase composition on the NPs' size, zeta potential and entrapment efficiency (EE%) using mixture designs. The obtained NPs were monodispersed with Z(ave)<300 nm and exhibited negative zeta potentials. For the single emulsion, the co-solvent concentration was shown to be the primary determinant of drug entrapment. The EE% increased from 14% to 22% by decreasing the amount of DMSO from 80% to 25% (v/v) in the organic polymer solution. For the double emulsion, EE% was 22% on average and independent of the organic phase composition. The double-emulsion technique did not enhance the aescin encapsulation as expected due to its amphiphilic nature. The optimised aescin loaded NPs meet the requirements for further in vitro activity tests. PMID- 22047549 TI - Mucoadhesive bilayer buccal tablet of carvedilol-loaded chitosan microspheres: in vitro, pharmacokinetic and pharmacodynamic investigations. AB - A multiple-unit system comprising mucoadhesive bilayer buccal tablets of carvedilol-loaded chitosan microspheres (CMs) was developed to improve bioavailability and therapeutic efficacy of carvedilol. Drug-loaded CMs were prepared by spray drying, evaluated for powder and particle characteristics, and optimized batch of CMs was compressed into bilayer buccal tablets using Carbopol. Tablets were evaluated for physicochemical parameters, in vitro drug release, in vivo pharmacokinetic and pharmacodynamic studies. Optimized formulation, CMT1 (CMT, chitosan microsphere tablet) showed maximum mucoadhesive force (50 +/- 1.84 dyne/cm2), exhibited 73.08 +/- 3.05% drug release and demonstrated zero-order kinetics with non-Fickian release mechanism. Pharmacokinetic studies in rabbits showed significantly higher C(max) (71.26 +/- 6.45 ng/mL), AUC(0-10) (AUC, area under the curve 390.75 +/- 5.23 ng/mL/h) and AUC(0-infinity) (664.72 ng/mL/h) than carvedilol oral tablet. Pharmacodynamic studies confirmed reduction in mean arterial pressure, heart rate, body weight and triglyceride on administration of bilayer buccal tablet compared to oral carvedilol tablet. Multiple-unit system exhibited enhanced bioavailability and sustained release of carvedilol, indicating its improved therapeutic potential for the treatment of hypertension. PMID- 22047550 TI - Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal tumor: a rare adverse event. AB - BACKGROUND: Imatinib mesylate has been the standard therapeutic treatment for chronic myeloid leukemia, advanced and metastatic gastrointestinal stromal tumor (GIST). It is well tolerated with mild adverse effects. Gynecomastia development during the course of treatment has been rarely reported. METHODS: Ninety-eight patients with advanced or recurrent GIST were treated with imatinib mesylate. Among the fifty-seven male patients six developed gynecomastia during the treatment. The lesions were confirmed by sonography. Sex hormone levels were determined in six patients with and without the presence of gynecomastia respectively. The patients with gynecomatia were treated with tamoxifene and the sex hormones were assayed before and after tamoxifene treatment. RESULTS: In patients with gynecomastia the lump underneath the bilateral nipples was 2.5 to 5 centimeters in diameter. Their serum free testosterone levels ranged between 356.61 and 574.60 ng/dl with a mean +/- SD of 408.64 +/- 82.06 ng/dl (95% CI 343.03~474.25 ng/dl), which is within the normal range. The level of serum estradiol was 42.89 +/- 16.54 pg/ml (95% CI 29.66~56.12 pg/ml). Three patients had higher levels (43.79~71.21 pg/ml) and the others' were within normal range of 27.00~34.91 pg/ml. Six patients without the development of gynecomastia had normal free testosterone. One patient died because of large tumor burden. The sex hormones had no significant changes before and after tamoxifene treatment.(P > 0.05) CONCLUSIONS: Testosterone levels were not decreased in the six GIST patients with gynecomastia. Three patients had increased serum estradiol level which suggests that imbalance of sex hormones may be the cause of gynecomastia during treatment with imatinib mesylate. PMID- 22047551 TI - Drug-loaded and superparamagnetic iron oxide nanoparticle surface-embedded amphiphilic block copolymer micelles for integrated chemotherapeutic drug delivery and MR imaging. AB - We report on the fabrication of organic/inorganic hybrid micelles of amphiphilic block copolymers physically encapsulated with hydrophobic drugs within micellar cores and stably embedded with superparamagnetic iron oxide (SPIO) nanoparticles within hydrophilic coronas, which possess integrated functions of chemotherapeutic drug delivery and magnetic resonance (MR) imaging contrast enhancement. Poly(epsilon-caprolactone)-b-poly(glycerol monomethacrylate), PCL-b PGMA, and PCL-b-P(OEGMA-co-FA) amphiphilic block copolymers were synthesized at first by combining ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and post- modification techniques, where OEGMA and FA are oligo(ethylene glycol) monomethyl ether methacrylate and folic acid-bearing moieties, respectively. A model hydrophobic anticancer drug, paclitaxel (PTX), and 4 nm SPIO nanoparticles were then loaded into micellar cores and hydrophilic coronas, respectively, of mixed micelles fabricated from PCL-b-PGMA and PCL-b P(OEGMA-co-FA) diblock copolymers by taking advantage of the hydrophobicity of micellar cores and strong affinity between 1,2-diol moieties in PGMA and Fe atoms at the surface of SPIO nanoparticles. The controlled and sustained release of PTX from hybrid micelles was achieved, exhibiting a cumulative release of ~61% encapsulated drugs (loading content, 8.5 w/w%) over ~130 h. Compared to that of surfactant-stabilized single SPIO nanoparticles (r(2) = 28.3 s(-1) mM(-1) Fe), the clustering of SPIO nanoparticles within micellar coronas led to considerably enhanced T(2) relaxivity (r(2) = 121.1 s(-1) mM(-1) Fe), suggesting that hybrid micelles can serve as a T(2)-weighted MR imaging contrast enhancer with improved performance. Moreover, preliminary experiments of in vivo MR imaging were also conducted. These results indicate that amphiphilic block copolymer micelles surface embedded with SPIO nanoparticles at the hydrophilic corona can act as a new generation of nanoplatform integrating targeted drug delivery, controlled release, and disease diagnostic functions. PMID- 22047552 TI - Insight into cross-talk between intra-amoebal pathogens. AB - BACKGROUND: Amoebae are phagocytic protists where genetic exchanges might take place between amoeba-resistant bacteria. These amoebal pathogens are able to escape the phagocytic behaviour of their host. They belong to different bacterial phyla and often show a larger genome size than human-infecting pathogens. This characteristic is proposed to be the result of frequent gene exchanges with other bacteria that share a sympatric lifestyle and contrasts with the genome reduction observed among strict human pathogens. RESULTS: We sequenced the genome of a new amoebal pathogen, Legionella drancourtii, and compared its gene content to that of a Chlamydia-related bacterium, Parachlamydia acanthamoebae. Phylogenetic reconstructions identified seven potential horizontal gene transfers (HGTs) between the two amoeba-resistant bacteria, including a complete operon of four genes that encodes an ABC-type transporter. These comparisons pinpointed potential cases of gene exchange between P. acanthamoebae and Legionella pneumophila, as well as gene exchanges between other members of the Legionellales and Chlamydiales orders. Moreover, nine cases represent possible HGTs between representatives from the Legionellales or Chlamydiales and members of the Rickettsiales order. CONCLUSIONS: This study identifies numerous gene exchanges between intracellular Legionellales and Chlamydiales bacteria, which could preferentially occur within common inclusions in their amoebal hosts. Therefore it contributes to improve our knowledge on the intra-amoebal gene properties associated to their specific lifestyle. PMID- 22047555 TI - Oxidative stress and leaf senescence. AB - BACKGROUND: Senescence is an important developmental process that leads to the cell death through highly regulated genetically controlled processes in plants. Biotic and abiotic Oxidative stresses can also artificially induce senescence and increase the production of reactive oxygen species (ROS) specifically in chloroplast. One of the important oxidative stresses is paraquat that induces deviation of electron from photosynthesis electron chain and lead to the production of more ROS in chloroplast. Plants have evolved special adoptive mechanism to reallocate nutrient to reproductive and juvenile organs in senescence and different oxidative stresses. Rubisco seems to be the most abundant protein in plants and is involved in many changes during senescence. RESULTS: In the present study, the effects of ROS on Rubisco during senescence and oxidative stresses were evaluated by measuring photosynthesis factors such as net photosynthesis rate (Pn), stomatal conductance (G), evaporation rate (E), intra cellular CO2 concentration (Ci), fluorescence and total protein during three stages of development. Our results showed that in paraquat treated plants, CO2 assimilation is the most effective factor that refers to Rubisco damages. The highest correlation and regression coefficient belonged to Ci, while correlation coefficient between photosynthesis rate and total protein was much smaller. CONCLUSION: It appears in the early stage of oxidative stresses such as exposing to paraquat, ROS has the most effect on Rubisco activity that induces more susceptibility to Rubisco specific protease. Moreover, Rubisco deactivation acts as an initiative signal for Rubisco degradation. PMID- 22047554 TI - Temperature dependence of the heat diffusivity of proteins. AB - In a combined experimental-theoretical study, we investigated the transport of vibrational energy from the surrounding solvent into the interior of a heme protein, the sperm whale myoglobin double mutant L29W-S108L, and its dependence on temperature from 20 to 70 K. The hindered libration of a CO molecule that is not covalently bound to any part of the protein but is trapped in one of its binding pockets (the Xe4 pocket) was used as the local thermometer. Energy was deposited into the solvent by IR excitation. Experimentally, the energy transfer rate increased from (30 ps)(-1) at 20 K to (8 ps)(-1) at 70 K. This temperature trend is opposite to what is expected, assuming that the mechanism of heat transport is similar to that in glasses. In order to elucidate the mechanism and its temperature dependence, nonequilibrium molecular dynamics (MD) simulations were performed, which, however, predicted an essentially temperature-independent rate of vibrational energy flow. We tentatively conclude that the MD potentials overestimate the coupling between the protein and the CO molecule, which appears to be the rate-limiting step in the real system at low temperatures. Assuming that this coupling is anharmonic in nature, the observed temperature trend can readily be explained. PMID- 22047556 TI - Toward the definition of stereochemical requirements for MT2-selective antagonists and partial agonists by studying 4-phenyl-2-propionamidotetralin derivatives. AB - New derivatives of 4-phenyl-2-propionamidotetralin (4-P-PDOT) were prepared and tested on cloned MT1 and MT2 receptors, with the purpose of merging previously reported pharmacophores for nonselective agonists and for MT2-selective antagonists. A 8-methoxy group increases binding affinity of both (+/-)-cis- and (+/-)-trans-4-P-PDOT, and it can be bioisosterically replaced by a bromine. Conformational analysis of 8-methoxy-4-P-PDOT by molecular dynamics, supported by NMR data, revealed an energetically favored conformation for the (2S,4S)-cis isomer and a less favorable conformation for the (2R,4S)-trans one, fulfilling the requirements of a pharmacophore model for nonselective melatonin receptor agonists. A new superposition model, including features characteristic of MT2 selective antagonists, suggests that MT1/MT2 agonists and MT2 antagonists can share the same arrangement for their pharmacophoric elements. The model correctly predicted the eutomers of (+/-)-cis- and (+/-)-trans-4-P-PDOT. The model was validated by preparing three dihydronaphthalene derivatives, either able or not able to reproduce the putative active conformation of 4-P-PDOT. PMID- 22047558 TI - Inducible apoptosis as a safety switch for adoptive cell therapy. AB - BACKGROUND: Cellular therapies could play a role in cancer treatment and regenerative medicine if it were possible to quickly eliminate the infused cells in case of adverse events. We devised an inducible T-cell safety switch that is based on the fusion of human caspase 9 to a modified human FK-binding protein, allowing conditional dimerization. When exposed to a synthetic dimerizing drug, the inducible caspase 9 (iCasp9) becomes activated and leads to the rapid death of cells expressing this construct. METHODS: We tested the activity of our safety switch by introducing the gene into donor T cells given to enhance immune reconstitution in recipients of haploidentical stem-cell transplants. Patients received AP1903, an otherwise bioinert small-molecule dimerizing drug, if graft versus-host disease (GVHD) developed. We measured the effects of AP1903 on GVHD and on the function and persistence of the cells containing the iCasp9 safety switch. RESULTS: Five patients between the ages of 3 and 17 years who had undergone stem-cell transplantation for relapsed acute leukemia were treated with the genetically modified T cells. The cells were detected in peripheral blood from all five patients and increased in number over time, despite their constitutive transgene expression. A single dose of dimerizing drug, given to four patients in whom GVHD developed, eliminated more than 90% of the modified T cells within 30 minutes after administration and ended the GVHD without recurrence. CONCLUSIONS: The iCasp9 cell-suicide system may increase the safety of cellular therapies and expand their clinical applications. (Funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; ClinicalTrials.gov number, NCT00710892.). PMID- 22047559 TI - Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors. AB - BACKGROUND: Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established. METHODS: We enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (+/-15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [+/-15%] used for bleeding episodes). The two treatment periods were separated by a 3-month washout period, during which patients received on-demand therapy for bleeding. The primary outcome was the number of bleeding episodes during each 6-month treatment period. RESULTS: Thirty four patients underwent randomization; 26 patients completed both treatment periods and could be evaluated per protocol for the efficacy analysis. As compared with on-demand therapy, prophylaxis was associated with a 62% reduction in all bleeding episodes (P<0.001), a 61% reduction in hemarthroses (P<0.001), and a 72% reduction in target-joint bleeding (>=3 hemarthroses in a single joint during a 6-month treatment period) (P<0.001). Thirty-three randomly assigned patients received at least one infusion of the study drug and were evaluated for safety. One patient had an allergic reaction to the study drug. CONCLUSIONS: AICC prophylaxis at the dosage evaluated significantly and safely decreased the frequency of joint and other bleeding events in patients with severe hemophilia A and factor VIII inhibitors. (Funded by Baxter BioScience; Pro-FEIBA ClinicalTrials.gov number, NCT00221195.). PMID- 22047557 TI - A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. AB - BACKGROUND: Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84 subjects, of whom 83 received at least one dose) or placebo (83, of whom 78 received at least one dose) for 48 weeks. The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second (FEV(1)). RESULTS: The change from baseline through week 24 in the percent of predicted FEV(1) was greater by 10.6 percentage points in the ivacaftor group than in the placebo group (P<0.001). Effects on pulmonary function were noted by 2 weeks, and a significant treatment effect was maintained through week 48. Subjects receiving ivacaftor were 55% less likely to have a pulmonary exacerbation than were patients receiving placebo, through week 48 (P<0.001). In addition, through week 48, subjects in the ivacaftor group scored 8.6 points higher than did subjects in the placebo group on the respiratory symptoms domain of the Cystic Fibrosis Questionnaire-revised instrument (a 100 point scale, with higher numbers indicating a lower effect of symptoms on the patient's quality of life) (P<0.001). By 48 weeks, patients treated with ivacaftor had gained, on average, 2.7 kg more weight than had patients receiving placebo (P<0.001). The change from baseline through week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor as compared with placebo was -48.1 mmol per liter (P<0.001). The incidence of adverse events was similar with ivacaftor and placebo, with a lower proportion of serious adverse events with ivacaftor than with placebo (24% vs. 42%). CONCLUSIONS: Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks. Substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride. (Funded by Vertex Pharmaceuticals and others; VX08-770-102 ClinicalTrials.gov number, NCT00909532.). PMID- 22047560 TI - Host and pathogen factors for Clostridium difficile infection and colonization. AB - BACKGROUND: Clostridium difficile infection is the leading cause of health care associated diarrhea, and the bacterium can also be carried asymptomatically. The objective of this study was to identify host and bacterial factors associated with health care-associated acquisition of C. difficile infection and colonization. METHODS: We conducted a 15-month prospective study in six Canadian hospitals in Quebec and Ontario. Demographic information, known risk factors, potential confounding factors, and weekly stool samples or rectal swabs were collected. Pulsed-field gel electrophoresis (PFGE) was performed on C. difficile isolates to determine the genotype. Levels of serum antibodies against C. difficile toxins A and B were measured. RESULTS: A total of 4143 patients were included in the study; 117 (2.8%) and 123 (3.0%) had health care-associated C. difficile infection and colonization, respectively. Older age and use of antibiotics and proton-pump inhibitors were significantly associated with health care-associated C. difficile infection. Hospitalization in the previous 2 months; use of chemotherapy, proton-pump inhibitors, and H(2) blockers; and antibodies against toxin B were associated with health care-associated C. difficile colonization. Among patients with health care-associated C. difficile infection and those with colonization, 62.7% and 36.1%, respectively, had the North American PFGE type 1 (NAP1) strain. CONCLUSIONS: In this study, health care associated C. difficile infection and colonization were differentially associated with defined host and pathogen variables. The NAP1 strain was predominant among patients with C. difficile infection, whereas asymptomatic patients were more likely to be colonized with other strains. (Funded by the Consortium de Recherche sur le Clostridium difficile.). PMID- 22047561 TI - Results of the Medicare Health Support disease-management pilot program. AB - BACKGROUND: In the Medicare Modernization Act of 2003, Congress required the Centers for Medicare and Medicaid Services to test the commercial disease management model in the Medicare fee-for-service program. METHODS: The Medicare Health Support Pilot Program was a large, randomized study of eight commercial programs for disease management that used nurse-based call centers. We randomly assigned patients with heart failure, diabetes, or both to the intervention or to usual care (control) and compared them with the use of a difference-in differences method to evaluate the effects of the commercial programs on the quality of clinical care, acute care utilization, and Medicare expenditures for Medicare fee-for-service beneficiaries. RESULTS: The study included 242,417 patients (163,107 in the intervention group and 79,310 in the control group). The eight commercial disease-management programs did not reduce hospital admissions or emergency room visits, as compared with usual care. We observed only 14 significant improvements in process-of-care measures out of 40 comparisons. These modest improvements came at substantial cost to the Medicare program in fees paid to the disease-management companies ($400 million), with no demonstrable savings in Medicare expenditures. CONCLUSIONS: In this large study, commercial disease management programs using nurse-based call centers achieved only modest improvements in quality-of-care measures, with no demonstrable reduction in the utilization of acute care or the costs of care. PMID- 22047562 TI - Ulcerative colitis. PMID- 22047563 TI - Images in clinical medicine. Lingual zoster. PMID- 22047564 TI - Clinical problem-solving. A bird's-eye view of fever. PMID- 22047565 TI - Therapy for cystic fibrosis--the end of the beginning? PMID- 22047566 TI - Eliminating cells gone astray. PMID- 22047567 TI - Calcium handling in the failing heart and SUMO--weighing the evidence. PMID- 22047569 TI - Wnt signaling and Dupuytren's disease. PMID- 22047571 TI - CYP24A1 mutations in idiopathic infantile hypercalcemia. PMID- 22047572 TI - CYP24A1 mutations in idiopathic infantile hypercalcemia. PMID- 22047574 TI - Constrictive bronchiolitis in soldiers. PMID- 22047575 TI - Constrictive bronchiolitis in soldiers. PMID- 22047576 TI - Constrictive bronchiolitis in soldiers. PMID- 22047578 TI - Bardoxolone methyl, chronic kidney disease, and type 2 diabetes. PMID- 22047579 TI - Bardoxolone methyl, chronic kidney disease, and type 2 diabetes. PMID- 22047580 TI - Bardoxolone methyl, chronic kidney disease, and type 2 diabetes. PMID- 22047581 TI - Bardoxolone methyl, chronic kidney disease, and type 2 diabetes. PMID- 22047582 TI - Hemophilia A induced by ipilimumab. PMID- 22047584 TI - Images in clinical medicine. Metastasis of renal-cell carcinoma. PMID- 22047590 TI - Measuring sexual function in community surveys: development of a conceptual framework. AB - Among the many psychometric measures of sexual (dys)function, none is entirely suited to use in community surveys. Faced with the need to include a brief and non-intrusive measure of sexual function in a general population survey, a new measure was developed. Findings from qualitative research with men and women in the community designed to inform the conceptual framework for this measure are presented. Thirty-two semi-structured interviews with individuals recruited from a general practice, an HIV/AIDS charity, and a sexual problems clinic were conducted. From their accounts, 31 potential criteria of a functional sex life were identified. Using evidence from qualitative data and the existing literature, and applying a set of decision rules, the list was reduced to 13 (eight for those not in a relationship), and a further eight criteria were added to enable individuals to self-rate their level of function and indicate the severity of difficulties. These criteria constitute a conceptual framework that is grounded in participant perceptions; is relevant to all, regardless of sexual experience or orientation; provides opportunity to state the degree of associated distress; and incorporates relational, psychological, and physiological aspects. It provides the conceptual basis for a concise and acceptable measure of sexual function. PMID- 22047591 TI - Searching for phenotypic causal networks involving complex traits: an application to European quail. AB - BACKGROUND: Structural equation models (SEM) are used to model multiple traits and the casual links among them. The number of different causal structures that can be used to fit a SEM is typically very large, even when only a few traits are studied. In recent applications of SEM in quantitative genetics mixed model settings, causal structures were pre-selected based on prior beliefs alone. Alternatively, there are algorithms that search for structures that are compatible with the joint distribution of the data. However, such a search cannot be performed directly on the joint distribution of the phenotypes since causal relationships are possibly masked by genetic covariances. In this context, the application of the Inductive Causation (IC) algorithm to the joint distribution of phenotypes conditional to unobservable genetic effects has been proposed. METHODS: Here, we applied this approach to five traits in European quail: birth weight (BW), weight at 35 days of age (W35), age at first egg (AFE), average egg weight from 77 to 110 days of age (AEW), and number of eggs laid in the same period (NE). We have focused the discussion on the challenges and difficulties resulting from applying this method to field data. Statistical decisions regarding partial correlations were based on different Highest Posterior Density (HPD) interval contents and models based on the selected causal structures were compared using the Deviance Information Criterion (DIC). In addition, we used temporal information to perform additional edge orienting, overriding the algorithm output when necessary. RESULTS: As a result, the final causal structure consisted of two separated substructures: BW->AEW and W35->AFE->NE, where an arrow represents a direct effect. Comparison between a SEM with the selected structure and a Multiple Trait Animal Model using DIC indicated that the SEM is more plausible. CONCLUSIONS: Coupling prior knowledge with the output provided by the IC algorithm allowed further learning regarding phenotypic causal structures when compared to standard mixed effects SEM applications. PMID- 22047592 TI - alpha7 Nicotinic receptor modulators for cognitive deficits in schizophrenia and Alzheimer's disease. AB - INTRODUCTION: Nicotinic receptors (nAChR), a class of ligand-gated ion channels, are attractive targets in a variety of CNS diseases. The low-affinity alpha7 nAChR modulate the levels of various neurotransmitters, their receptor density is affected in schizophrenia and a single nucleotide polymorphism in the promoter region has been associated with higher risk for schizophrenia. AREAS COVERED: This article reviews the scientific rationale for alpha7 nAChR stimulation and presents a selection of alpha7-positive modulators that are in development for cognitive deficits, both in Alzheimer's disease and in cognitive impairment associated with schizophrenia. The available clinical information is reviewed and the translational difficulties are discussed. EXPERT OPINION: In contrast to preclinical models, clinical proof-of-concept studies so far have not shown clear unequivocal cognitive benefit, although there are signs of clinical efficacy on specific cognitive scales and on negative symptoms. Possible problems associated with the clinical development include the impact of dosage and dosing schedule on the balance between activation and desensitization of the ion channel, the selection of comedication, robust human target engagement data and the choice of clinical readout scales. A better understanding of the human biology of alpha7 nAChR is essential for improving the successful clinical development of this promising target. PMID- 22047593 TI - Contribution of spin and anisotropy to single molecule magnet behavior in a family of bell-shaped Mn11Ln2 coordination clusters. AB - The synthesis, structures, and magnetic properties of a family of isostructural "bell-shaped" heterometallic coordination clusters [Mn(III)(9)Mn(II)(2)La(III)(2)(MU(4)-O)(7)(MU(3)-O)(MU(3) OH)(2)(piv)(10.8)(O(2)CC(4)H(3)O)(6.2)(NO(3))(2)(OH(2))(1.5)(MeCN)(0.5)].12CH(3)C .2H(2)O (1) and [Mn(III)(9)Mn(II)(2)Ln(2)(MU(4)-O)(7)(MU (3)-O)(MU(3) OH)(2)(piv)(10.6)(O(2)CC(4)H(3)O)(6.4)(NO(3))(2)(OH(2))].nCH(3)CN.H(2)O (Ln = Pr(III), n = 8 (2); Ln = Nd(III), n = 10 (3); Ln = Eu(III), n = 17 (4); Ln = Gd(III), n = 13 (5); piv = pivalate) are reported. The complexes were obtained from the reaction of [Mn(III)(2)Mn(II)(4)O(2)(piv)(10)(4-Me-py)(2.5)(pivH)(1.5)] and Ln(NO(3))(3).6H(2)O in the presence of 2-furan-carboxylic acid (C(4)H(3)OCOOH) in CH(3)CN. Compounds 1-5 are isomorphous, crystallizing in the triclinic space group P1 with Z = 2. The Mn(III) and Mn(II) centers together form the shell of the bell, while the two Ln(III) centers can be regarded as the bell's clapper. The magnetic properties of 1-4 reveal dominant antiferromagnetic interactions between the magnetic centers leading to small spin ground states; while those of 5 indicate similar antiferromagnetic interactions between the manganese ions but with unusually strong ferromagnetic interactions between the Gd(III) ions leading to a large overall spin ground state of S = 11-12. While ac and dc magnetic measurements confirmed that Mn(11)Gd(2) (5) is a single-molecule magnet (SMM) showing hysteresis loops at low temperatures, compounds 1-4 do not show any slow relaxation of the magnetization, indicating that the S = 7 spin of the ferromagnetic Gd(2) unit in 5 is a necessary contribution to its SMM behavior. PMID- 22047594 TI - Ertapenem for treatment of osteomyelitis: a case series. AB - BACKGROUND: Ertapenem is a once-daily broad spectrum carbapenem that is increasingly used to treat polymicrobial osteomyelitis due to diabetic foot and traumatic wound infections. However, limited data exists on ertapenem use for osteomyelitis. This study aimed to characterize outcomes and adverse effects with empiric use of ertapenem for osteomyelitis. FINDINGS: A total of 112 patients presenting to Duke, Durham Regional or Durham VA Medical Centers with a suspected diagnosis of osteomyelitis and ertapenem use from 11/2001 to 8/2009 were screened, and 12 subjects met inclusion criteria for the study. Mean age was 60 +/- 16 years, 68% were female, 75% were Caucasian, and the most common comorbidities included diabetes (58%), peripheral vascular disease (42%), and history of tobacco use (75%). Over half of the patients presented to a primary care clinic or emergency room greater than six months after the onset of clinical symptoms. Bone culture was obtained for diagnostic guidance in only two cases; and surgical intervention was pursued in three cases. Patients received a mean duration of 34.6 +/- 7.8 days of therapy, and in three cases, subsequent suppressive oral antibiotics were given. Six (50%) patients met criteria for clinical success, defined as resolution of clinical signs and symptoms of infection such that discontinuation of antibiotics was deemed appropriate at end of ertapenem therapy, without recurrence at one year follow-up. No adverse drug effects were noted. CONCLUSIONS: In this case series of mostly community acquired, lower extremity osteomyelitis, bone biopsy was infrequent, and an average six-week course of empiric ertapenem was well-tolerated with curative rates of 50% at one year. PMID- 22047595 TI - A multidisciplinary survey on controversies in the use of EUS-guided FNA: assessing perspectives of surgeons, oncologists and gastroenterologists. AB - BACKGROUND: EUS-guided FNA can help diagnose and differentiate between various pancreatic and other lesions.The aim of this study was to compare approaches among involved/relevant physicians to the controversies surrounding the use of FNA in EUS. METHODS: A five-case survey was developed, piloted, and validated. It was collected from a total of 101 physicians, who were all either gastroenterologists (GIs), surgeons or oncologists. The survey compared the management strategies chosen by members of these relevant disciplines regarding EUS-guided FNA. RESULTS: For CT operable T2NOM0 pancreatic tumors the research demonstrated variance as to whether to undertake EUS-guided FNA, at p < 0.05. For inoperable pancreatic tumors 66.7% of oncologists, 62.2% of surgeons and 79.1% of GIs opted for FNA (p < 0.05). For cystic pancreatic lesions, oncologists were more likely to send patients to surgery without FNA. For stable simple pancreatic cysts (23 mm), most physicians (66.67%) did not recommend FNA. For a submucosal gastric 19 mm lesion, 63.2% of surgeons recommended FNA, vs. 90.0% of oncologists (p < 0.05). CONCLUSIONS: Controversies as to ideal application of EUS-FNA persist. Optimal guidelines should reflect the needs and concerns of the multidisciplinary team who treat patients who need EUS-FNA. Multi-specialty meetings assembled to manage patients with these disorders may be enlightening and may help develop consensus. PMID- 22047596 TI - Negative faradaic resistance in extracellular electron transfer by anode respiring Geobacter sulfurreducens cells. AB - Geobacter sulfurreducens is a gram-negative delta-proteobacterium that is capable of transferring respiratory electrons to solid-state extracellular acceptors, including anodes, via abundant c-type cytochromes expressed in the outer membrane. As extracellular electron transfer (EET) to solid-state acceptors can proceed without the addition of exogenous mediators, this microbe has attracted significant attention with respect to energy conversion between electrical and chemical energy. Here, we revealed that clear redox peaks were present in the whole-cell cyclic voltammogram of G. sulfurreducens at around -0.15 V vs Ag|AgCl when tin-doped In(2)O(3) (ITO) glass was used as an anode. Interestingly, the EET current decreased in the potential region more positive than the midpoint potential (E(m)) of the redox peak. Thus, EET of anode-respiring G. sulfurreducens cells exhibited a negative Faradaic resistance (NFR) characteristic at the E(m) of the redox peak, in contrast to general electrochemical systems where the Faradaic current typically increases with increasing overpotential. PMID- 22047597 TI - The effect of 670-nm low laser therapy on herpes simplex type 1. AB - OBJECTIVE: The purpose of this work was to study the effect of low-level laser therapy (LLLT) on the healing and relapse intervals in patients with recurrent labial herpes simplex infections. BACKGROUND DATA: Several pharmaceuticals are available to reduce symptoms and improbe healing of labial herpes, but only LLLT has been reported to significantly influence the length of the recurrence period. MATERIAL AND METHODS: In an initial study, 232 patients with herpes simplex type 1 virus symptoms were consecutively selected for either LLLT or conventional therapy, including acyclovir cream or tablets. One of the dentists was responsible for the diagnosis, a second dentist for the treatment, and and a third for the evaluation, to allow for a semi-blinded procedure. Patients in the laser group received 670-nm laser irradiation, 40 mW, 1.6 J, 2.04 J/cm(2), 51 mW/cm(2) per blister in the prodromal stage and 4.8 J in the crust and secondarily infected stages, plus 1.2 J at the C2-C3 vertebrae. Patients were monitored daily during the first week to control healing, and monthly for 1 year to check on recurrence. In a consecutive study, 322 patients receiving LLLT were followed during 5 years to observe the period of ocurrences. RESULTS: An obvious effect of LLLT was found for both initial healing and for the length of the recurrence periods. CONCLUSIONS: LLLTof herpes simples virus 1 (HSV-1) appears to be an effective treatment modality without any observed side effects. PMID- 22047598 TI - Focal increase in cerebral blood flow after treatment with near-infrared light to the forehead in a patient in a persistent vegetative state. AB - OBJECTIVE: This study aimed to quantify the cerebral blood flow (CBF) after bilateral, transcranial near-infrared light-emitting diode (LED) irradiation to the forehead in a patient in a persistent vegetative state following severe head injury. BACKGROUND DATA: Positive behavioral improvement has been observed following transcranial near-infrared light therapy in humans with chronic traumatic brain injury and acute stroke. METHODS: Single-photon emission computed tomography with N-isopropyl-[123I]p-iodoamphetamine (IMP-SPECT) was performed following a series of LED treatments. RESULTS: IMP-SPECT showed unilateral, left anterior frontal lobe focal increase of 20%, compared to the pre-treatment value for regional CBF (rCBF) for this area, following 146 LED treatments over 73 days from an array of 23*850 nm LEDs, 13 mW each, held 5 mm from the skin, 30 min per session, the power density 11.4 mW/cm(2); the energy density 20.5 J/cm(2) at the skin. The patient showed some improvement in his neurological condition by moving his left arm/hand to reach the tracheostomy tube, post-LED therapy. CONCLUSIONS: Transcranial LED might increase rCBF with some improvement of neurological condition in severely head-injured patients. Further study is warranted. PMID- 22047599 TI - Treatment of perianal condyloma acuminate with topical ALA-PDT combined with curettage: outcome and safety. AB - OBJECTIVE: The purpose of this study was to evaluate the treatment outcome and safety of topical photodynamic therapy (PDT) with aminolevulinic acid (5-ALA) combined with surgical curettage for perianal condyloma acuminata. BACKGROUND DATA: Condyloma acuminata is the most common sexually transmitted disease, with a high relapse rate, especially in the perianal area. The outcomes of many treatment methods for perianal genital warts are not satisfactory. METHODS: In this study, 40 cases of perianal condyloma acuminata were treated with topical aminolevulinic acid photodynamic therapy (ALA-PDT) combined with curettage. First, the warts were removed with the patient under local anesthesia. The depth of the ablation and curettage reached the dermal layer. Then, the first session of PDT was performed after 2 days. Ten percent 5-ALA cream was applied to lesional skin with occlusive dressing for a 3-h incubation period and the lesions of warts were irradiated for 10 min by using a 635-nm laser beam of 177 mW/cm(2) intensity. The ALA-PDT was repeated after 1 and 3 weeks. Follow-up evaluation was performed at our outpatient clinic at 1 and 3 months after completion of therapy. Before treatment and at each follow-up visit, the lesions were photographed; the treatment outcome was evaluated as recurrence rate, and patient satisfaction was surveyed. RESULTS: After three PDT sessions following surgical curettage, all 40 patients were cured and there was no recurrence at 1 month off treatment. At 3 months off treatment, six cases relapsed, corresponding to a recurrent rate of 15%. The satisfaction rate of patients was 100% at 1 month and 95% at 3 months after treatment. CONCLUSIONS: Combination of surgical curettage and topical PDT has been proven to be a safe and effective procedure, and may offer a wide clinical application for the treatment of perianal condyloma acuminata. PMID- 22047600 TI - Building the capacity of family day care educators to promote children's social and emotional wellbeing: an exploratory cluster randomised controlled trial. AB - BACKGROUND: Childhood mental health problems are highly prevalent, experienced by one in five children living in socioeconomically disadvantaged families. Although childcare settings, including family day care are ideal to promote children's social and emotional wellbeing at a population level in a sustainable way, family day care educators receive limited training in promoting children's mental health. This study is an exploratory wait-list control cluster randomised controlled trial to test the appropriateness, acceptability, cost, and effectiveness of "Thrive," an intervention program to build the capacity of family day care educators to promote children's social and emotional wellbeing. Thrive aims to increase educators' knowledge, confidence and skills in promoting children's social and emotional wellbeing. METHODS/DESIGN: This study involves one family day care organisation based in a low socioeconomic area of Melbourne. All family day care educators (term used for registered carers who provide care for children for financial reimbursement in the carers own home) are eligible to participate in the study. The clusters for randomisation will be the fieldworkers (n = 5) who each supervise 10-15 educators. The intervention group (field workers and educators) will participate in a variety of intervention activities over 12 months, including workshops; activity exchanges with other educators; and focused discussion about children's social and emotional wellbeing during field worker visits. The control group will continue with their normal work practice. The intervention will be delivered to the intervention group and then to the control group after a time delay of 15 months post intervention commencement. A baseline survey will be conducted with all consenting educators and field workers (n = ~70) assessing outcomes at the cluster and individual level. The survey will also be administered at one month, six months and 12 months post-intervention commencement. The survey consists of questions measuring perceived levels of knowledge, confidence and skills in promoting children's social and emotional wellbeing. As much of this intervention will be delivered by field workers, field worker-family day care educator relationships are key to its success and thus supervisor support will also be measured. All educators will also have an in-home quality of care assessment at baseline, one month, six months and 12 months post intervention commencement. Process evaluation will occur at one month, six months and 12 months post-intervention commencement. Information regarding intervention fidelity and economics will also be assessed in the survey. DISCUSSION: A capacity building intervention in child mental health promotion for family day care is an essential contribution to research, policy and practice. This initiative is the first internationally, and essential in building an evidence base of interventions in this extremely policy-timely setting. TRIAL REGISTRATION NUMBER: 343312. PMID- 22047601 TI - SNOntology: Myriads of novel snoRNAs or just a mirage? AB - BACKGROUND: Small nucleolar RNAs (snoRNAs) are a large group of non-coding RNAs (ncRNAs) that mainly guide 2'-O-methylation (C/D RNAs) and pseudouridylation (H/ACA RNAs) of ribosomal RNAs. The pattern of rRNA modifications and the set of snoRNAs that guide these modifications are conserved in vertebrates. Nearly all snoRNA genes in vertebrates are localized in introns of other genes and are processed from pre-mRNAs. Thus, the same promoter is used for the transcription of snoRNAs and host genes. RESULTS: The series of studies by Dahai Zhu and coworkers on snoRNAs and their genes were critically considered. We present evidence that dozens of species-specific snoRNAs that they described in vertebrates are experimental artifacts resulting from the improper use of Northern hybridization. The snoRNA genes with putative intrinsic promoters that were supposed to be transcribed independently proved to contain numerous substitutions and are, most likely, pseudogenes. In some cases, they are localized within introns of overlooked host genes. Finally, an increased number of snoRNA genes in mammalian genomes described by Zhu and coworkers is also an artifact resulting from two mistakes. First, numerous mammalian snoRNA pseudogenes were considered as genes, whereas most of them are localized outside of host genes and contain substitutions that question their functionality. Second, Zhu and coworkers failed to identify many snoRNA genes in non-mammalian species. As an illustration, we present 1352 C/D snoRNA genes that we have identified and annotated in vertebrates. CONCLUSIONS: Our results demonstrate that conclusions based only on databases with automatically annotated ncRNAs can be erroneous. Special investigations aimed to distinguish true RNA genes from their pseudogenes should be done. Zhu and coworkers, as well as most other groups studying vertebrate snoRNAs, give new names to newly described homologs of human snoRNAs, which significantly complicates comparison between different species. It seems necessary to develop a uniform nomenclature for homologs of human snoRNAs in other vertebrates, e.g., human gene names prefixed with several-letter code denoting the vertebrate species. PMID- 22047602 TI - Development of a cultivation process for the enhancement of human interferon alpha 2b production in the oleaginous yeast, Yarrowia lipolytica. AB - BACKGROUND: As an oleaginous yeast, Yarrowia lipolytica is able to assimilate hydrophobic substrates. This led to the isolation of several promoters of key enzymes of this catabolic pathway. Less is known about the behavior of Y. lipolytica in large bioreactors using these substrates. There is therefore a lack of established know-how concerning high cell density culture protocols of this yeast. Consequently, the establishment of suitable induction conditions is required, to maximize recombinant protein production under the control of these promoters. RESULTS: Human interferon alpha2b (huIFN alpha2b) production in Yarrowia lipolytica was used as a model for the enhancement of recombinant protein production under the control of the oleic acid (OA)-inducible promoter POX2. Cell viability and heterologous protein production were enhanced by exponential glucose feeding, to generate biomass before OA induction. The optimal biomass level before induction was determined (73 g L(-1)), and glucose was added with oleic acid during the induction phase. Several oleic acid feeding strategies were assessed. Continuous feeding with OA at a ratio of 0.02 g OA per g dry cell weight increased huIFNalpha2b production by a factor of 1.88 (425 mg L(-1)) and decreased the induction time (by a factor of 2.6, 21 h). huIFN alpha2b degradation by an aspartic protease secreted by Y. lipolytica was prevented by adding pepstatin (10 MUM), leading to produce a 19-fold more active huIFN alpha2b (26.2 * 10(7) IU mg(-1)). CONCLUSION: Y. lipolytica, a generally regarded as safe (GRAS) microorganism is one of the most promising non conventional yeasts for the production of biologically active therapeutic proteins under the control of hydrophobic substrate-inducible promoter. PMID- 22047603 TI - Aligning nanodiscs at the air-water interface, a neutron reflectivity study. AB - Nanodiscs are self-assembled nanostructures composed of a belt protein and a small patch of lipid bilayer, which can solubilize membrane proteins in a lipid bilayer environment. We present a method for the alignment of a well-defined two dimensional layer of nanodiscs at the air-water interface by careful design of an insoluble surfactant monolayer at the surface. We used neutron reflectivity to demonstrate the feasibility of this approach and to elucidate the structure of the nanodisc layer. The proof of concept is hereby presented with the use of nanodiscs composed of a mixture of two different lipid (DMPC and DMPG) types to obtain a net overall negative charge of the nanodiscs. We find that the nanodisc layer has a thickness or 40.9 +/- 2.6 A with a surface coverage of 66 +/- 4%. This layer is located about 15 A below a cationic surfactant layer at the air water interface. The high level of organization within the nanodiscs layer is reflected by a low interfacial roughness (~4.5 A) found. The use of the nanodisc as a biomimetic model of the cell membrane allows for studies of single membrane proteins isolated in a confined lipid environment. The 2D alignment of nanodiscs could therefore enable studies of high-density layers containing membrane proteins that, in contrast to membrane proteins reconstituted in a continuous lipid bilayer, remain isolated from influences of neighboring membrane proteins within the layer. PMID- 22047604 TI - Positioning of bound electron wave packets in molecules revealed by high-harmonic spectroscopy. AB - By solution of the time-dependent two-electron Schrodinger equation, we demonstrate that strong-field ionization in combination with electron correlation can localize bound electron wave packets in molecules. The wave packet creation is revealed by the emission spectrum in high-order harmonic generation, which is sensitive to the ionization and recombination phase difference between different ionization channels. For hydrogen molecules at stretched internuclear distance, we find that the ionization phase difference between the gerade and ungerade channels is in the range from pi and 1.5pi, indicating that the bound wave packet either is initially on the same side as the outgoing electron or is delocalized. PMID- 22047605 TI - Spectral characterization of guanine C4-OH adduct: a radiation and quantum chemical study. AB - The reaction of hydroxyl radical ((*)OH) with guanine was investigated under restricted pH condition (pH 4.6) using pulse radiolysis technique. The time resolved optical transient absorption spectra showed two peaks centered at 300 and 330 nm at 4 MUs after the pulse which exhibited different reactivity toward molecular oxygen (O(2)). The peak at 300 nm was found to be relatively more stable than the peak at 330 nm. The peak corresponding to 330 nm decayed within 20 MUs having a first order rate constant 4-7 * 10(4) s(-1) and was pH dependent. On longer time scale, the species decayed by a bimolecular process. The presence of O(2) did not affect its decay rate constant. The (*)OH reacts with guanine at pH 4.6 with a diffusion-controlled second order rate constant of >=1 * 10(10) mol(-1) dm(3) s(-1). The reaction of Br(2)(*-), O(2)(*-), and 2-hydroxy-2-propyl radical with guanine was also investigated to differentiate among the one electron oxidized, one-electron reduced species of guanine and the guanine-OH adducts formed in the reaction of (*)OH at pH 4.6. On the basis of the spectral characteristics and reactivity toward O(2), two guanine-OH adduct species were identified (i) the C4-OH adduct species absorbing at 330 nm which has not been reported so far and (ii) the C8-OH adduct species absorbing at 300 nm in agreement with the known literature absorption features. Quantum chemical calculations using BHandHLYP with 6-31+G(d,p) basis set and excited state calculations using TDDFT for all possible transients complement the assignment of the observed spectral peak at 330 nm to the C4-OH adduct of guanine. Furthermore, steady state radiolysis revealed the formation of 8-hydroxy-guanine whose precursor is known to be the C8-OH adduct species. PMID- 22047606 TI - Targeting the binding function 3 (BF3) site of the human androgen receptor through virtual screening. AB - The androgen receptor (AR) is the best studied drug target for the treatment of prostate cancer. While there are a number of drugs that target the AR, they all work through the same mechanism of action and are prone to the development of drug resistance. There is a large unmet need for novel AR inhibitors which work through alternative mechanism(s). Recent studies have identified a novel site on the AR called binding function 3 (BF3) that is involved into AR transcriptional activity. In order to identify inhibitors that target the BF3 site, we have conducted a large-scale in silico screen followed by experimental evaluation. A number of compounds were identified that effectively inhibited the AR transcriptional activity with no obvious cytotoxicity. The mechanism of action of these compounds was validated by biochemical assays and X-ray crystallography. These findings lay a foundation for the development of alternative or supplementary therapies capable of combating prostate cancer even in its antiandrogen resistant forms. PMID- 22047607 TI - A strategy for emergency treatment of Schistosoma japonicum-infested water. AB - BACKGROUND: Schistosomiasis japonica, caused by contact with Schistosoma japonicum cercaria-infested water when washing, bathing or production, remains a major public-health concern in China. The purpose of the present study was to investigate the effect of a suspension concentrate of niclosamide (SCN) on killing cercaria of S. japonicum that float on the water surface, and its toxicity to fish, so as to establish an emergency-treatment intervention for rapidly killing cercaria and eliminating water infectivity. RESULTS: At 30 min after spraying 100 mg/L SCN, with niclosamide dosages of 0.01, 0.02, 0.03, 0.04 g/m2, the water infectivity reduced significantly and no infectivity was found at 60 min after spraying SCN. The surface of static water was sprayed with 100 mg/L SCN, the peak concentration was found at 0 min, and the solution diffused to site with a water depth of 10 cm after 10 min. 30 min later, SCN diffused to the whole water body, and distributed evenly. After spraying 100 mg/L SCN onto the surface of the water with a volume of(3.14 * 202 * 50)cm3, with niclosamide dosages of 0.02 g/m2, 96 h later, no death of zebra fish was observed. CONCLUSIONS: By spraying 100 mg/L SCN, with a niclosamide dosage of 0.02 g/m2 onto the surface of S. japonicum-infested water, infectivity of the water can be eliminated after 30 60 min, and there is no evident toxicity to fish. This cercaria-killing method, as an emergency-treatment intervention for infested water, can be applied in those forecasting and early warning systems for schistosomiasis. PMID- 22047608 TI - Tumor necrosis factor (TNF)-alpha upregulates progesterone receptor-A by activating the NF-kappaB signaling pathway in human decidua after labor onset. AB - To date, the relationship between inflammatory cytokines and progesterone receptors (PRs) has been little studied, although both mediate the mechanism of parturition in human deciduas. Thus, the aim of study was to investigate the role of an inflammatory cytokine, tumor necrosis factor (TNF)-alpha, in regulating progesterone withdrawal in decidua at human parturition. TNF-alpha levels and PR isoforms were compared in intrauterine deciduas from women who were in labor (IL, n = 10) or who were not in labor (NIL, n = 10). Nuclear factor-kappaB (NF-kappaB) signaling and PR status were analyzed in NIL deciduas after TNF-alpha stimulation. Immunohistochemistry, western blotting, ELISA and reverse transcription-polymerase chain reaction (RT-PCR) were used to localize and quantitate protein and mRNA expression. TNF-alpha immunostaining, protein levels, PR-A/PR-B ratio and COX-2 level were significantly higher in IL deciduas (all P < 0.05). NF-kappaB was activated by TNF-alpha after 24 h stimulation in a dose dependent manner, and was significantly inactivated by the NF-kappaB inhibitor panepoxydone, which was associated with decreased PR-A and COX-2 expression (P < 0.05) in not in labor deciduas. In conclusion, TNF-alpha may have an important role in regulating progesterone withdrawal in human decidua following labor onset. PMID- 22047609 TI - The impact of comorbid cannabis use disorders on the clinical presentation of social anxiety disorder. AB - Previous research has examined the relationship between social anxiety disorder (SAD) and substance use disorders. Cannabis use disorders (CUDs) are becoming increasingly problematic within the population of individuals with SAD, yet the nature of this comorbidity remains largely unexamined. The aim of the current study from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project was to examine differences between outpatients with SAD with versus without comorbid CUDs. The current study included 873 outpatients with a current diagnosis of SAD. Patients with SAD and comorbid CUDs (n = 173) were then compared to those with SAD without CUDs (n = 700) on demographic and clinical characteristics. Compared to patients without the comorbidity, patients with comorbid SAD and CUDs were more likely to have a lifetime diagnosis of PTSD and specific phobia and lifetime substance use disorders (including alcohol). SAD patients with comorbid CUDs were also more likely to report better physical health, and fewer limitations related to their physical health. These analyses remained significant after controlling for gender, the presence of other substance use disorders, mood disorders, and other anxiety disorders. Findings of this study suggest that there may be a unique relationship between SAD and CUDs that can potentially impact the clinical presentation of individuals with SAD. Future research is needed to examine the impact of this comorbidity in other patient populations. PMID- 22047610 TI - Consumers' salient beliefs regarding dairy products in the functional food era: a qualitative study using concepts from the theory of planned behaviour. AB - BACKGROUND: Inadequate consumption of dairy products without appropriate dietary substitution may have deleterious health consequences. Social research reveals the factors that may impede compliance with dietary recommendations. This is particularly important given the recent introduction of functional dairy products. One of the challenges for public health professionals is to demonstrate the efficacy of nutrition education in improving attitudes toward nutrient rich foods. The aim of this study was to explore the salient beliefs of adult weight loss trial participants regarding both traditional and functional dairy products and to compare these with a control group not exposed to nutrition education. METHODS: Six focus groups were conducted, three with weight loss trial completers (n = 15) that had received nutrition education and three with individuals from the same region (n = 14) to act as controls. Transcribed focus groups were coded using the Theory of Planned Behaviour theoretical framework. RESULTS: Non-trial participants perceived dairy foods as weight inducing and were sceptical of functional dairy products. A lack of time/ability to decipher dairy food labels was also discussed by these individuals. In contrast trial participants discussed several health benefits related to dairy foods, practised label reading and were confident in their ability to incorporate dairy foods into their diet. Normative beliefs expressed were similar for both groups indicating that these were more static and less amenable to change through nutrition education than control and behavioural beliefs. CONCLUSIONS: Nutrition education provided as a result of weight loss trial participation influenced behavioural and control beliefs relating to dairy products. This study provides a proof of concept indication that nutrition education may improve attitudes towards dairy products and may thus be an important target for public health campaigns seeking to increase intake of this food group. PMID- 22047611 TI - Control of the photocatalytic activity of bimetallic complexes of pyropheophorbide-a by nucleic acids. AB - Photocatalytic activity of a photosensitizer (PS) in an oligodeoxyribonucleotide duplex 5'-PS~ODN1/ODN2~Q-3' is inhibited because of close proximity of a quencher Q. The ODN2 in this duplex is selected to be longer than the ODN1. Therefore, in the presence of a nucleic acid (analyte), which is fully complementary to the ODN2 strand, the duplex is decomposed with formation of an analyte/ODN2~Q duplex and a catalytically active, single stranded PS~ODN1. In this way the catalytic activity of the PS can be controlled by the specific nucleic acids. We applied this reaction earlier for the amplified detection of ribonucleic acids in live cells (Arian, D.; Clo, E.; Gothelf, K.; Mokhir, A. Chem.-Eur. J.2010, 16(1), 288). As a photosensitizer (PS) we used In(3+)(pyropheophorbide-a)chloride and as a quencher (Q)--Black-Hole-Quencher-3 (BHQ-3). The In(3+) complex is a highly active photocatalyst in aqueous solution. However, it can coordinate additional ligands containing thiols (e.g., proteins, peptides, and aminoacids), that modulate properties of the complex itself and of the corresponding bio- molecules. These possible interactions can lead to undesired side effects of nucleic acid controlled photocatalysts (PS~ODN1/ODN2~Q) in live cells. In this work we explored the possibility to substitute the In(3+) complex for those ones of divalent metal ions, Zn(2+) and Pd(2+), which exhibit lower or no tendency to coordinate the fifth ligand. We found that one of the compounds tested (Pd(pyropheophorbide-a) is as potent and as stable photosensitizer as its In(3+) analogue, but does not coordinate additional ligands that makes it more suitable for cellular applications. When the Pd complex was introduced in the duplex PS~ODN1/ODN2~Q as a PS, its photocatalytic activity could be controlled by nucleic acids as efficiently as that of the corresponding In(3+) complex. PMID- 22047612 TI - Northeastern Section of the American Urological Association 63(rd) Annual Meeting, New Orleans, Louisiana October 26 - 30, 2011 Scientific Program. PMID- 22047613 TI - Products of SO2 adsorption on fuel cell electrocatalysts by combination of sulfur K-edge XANES and electrochemistry. AB - Electrochemical adsorption of SO(2) on platinum is complicated by the change in sulfur oxidation state with potential. Here, we attempt to identify SO(2) adsorption products on catalyst coated membranes (CCMs) at different electrode potentials using a combination of in situ sulfur K-edge XANES (X-ray absorption near-edge structure) spectroscopy and electrochemical techniques. CCMs employed platinum nanoparticles supported on Vulcan carbon (Pt/VC). SO(2) was adsorbed from a SO(2)/N(2) gas mixture while holding the Pt/VC-electrode potential at 0.1, 0.5, 0.7, and 0.9 V vs a reversible hydrogen electrode (RHE). Sulfur adatoms (S(0)) are identified as the SO(2) adsorption products at 0.1 V, while mixtures of S(0), SO(2), and sulfate/bisulfate ((bi)sulfate) ions are suggested as SO(2) adsorption products at 0.5 and 0.7 V. At 0.9 V, SO(2) is completely oxidized to (bi)sulfate ions. The identity of adsorbed SO(2) species on Pt/VC catalysts at different electrode potentials is confirmed by modeling of XANES spectra using FEFF8 and a linear combination of experimental spectra from sulfur standards. Results on SO(2) speciation gained from XANES are used to compare platinum-sulfur electronic interactions for Pt(3)Co/VC versus Pt/VC catalysts in order to understand the difference between the two catalysts in terms of SO(2) contamination. PMID- 22047614 TI - A case of hybrid closure of a muscular ventricular septal defect: anatomical complexity and surgical management. AB - Complex muscular ventricular septal defect poses difficult surgical management and is associated with high morbidity and mortality despite advancements in surgical therapy. Device closure of muscular ventricular septal defect has been encouraging and has been used in hybrid approach at a few centres. However, device closure has some limitations in patients with complex muscular ventricular septal defect. We report a case of perventricular device closure of a complex muscular ventricular septal defect in a beating heart with entrapped right ventricular disc and its surgical management. PMID- 22047615 TI - Modifications of the metabolic pathways of lipid and triacylglycerol production in microalgae. AB - Microalgae have presented themselves as a strong candidate to replace diminishing oil reserves as a source of lipids for biofuels. Here we describe successful modifications of terrestrial plant lipid content which increase overall lipid production or shift the balance of lipid production towards lipid varieties more useful for biofuel production. Our discussion ranges from the biosynthetic pathways and rate limiting steps of triacylglycerol formation to enzymes required for the formation of triacylglycerol containing exotic lipids. Secondarily, we discuss techniques for genetic engineering and modification of various microalgae which can be combined with insights gained from research in higher plants to aid in the creation of production strains of microalgae. PMID- 22047617 TI - Organochlorine contaminants in the hair of Iranian pregnant women. AB - In the present study, the hair of pregnant women was sampled between November 2007 and January 2008 in Ahvaz and Noushahr cities and the countryside of Noushahr, Iran. They were analyzed for organochlorine pesticides (OCPs), such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene (HCB), alpha-, beta-, and gamma-hexachlorocyclohexane (HCH) isomers and seven polychlorinated (PCBs) congeners (IUPAC Nos. 28, 52, 101, 118, 138, 153 and 180). Significant differences between the concentrations of investigated pollutants were found between the locations (p<0.05). For HCHs, the gamma-HCH isomer was measured at higher mean concentrations (6 ng g(-1) hair) compared to the beta-HCH isomer (0.03 ng g(-1)), which generally is the most prevalent HCH in biological matrices. Very high mean concentrations of p,p'-DDT in countryside of Noushahr (24 ng g(-1)) combined with lower values (0.6) of ratio p,p'-DDE/p,p'-DDT in the hair samples suggest recent exposure to "fresh" DDT in this region. Significant differences in OCPs and PCBs were found between primiparous and multiparous mothers (p<0.05). There was no correlation between levels of OCPs and PCBs in the hair of Iranian pregnant women and their age. There was a significant difference (p<0.05) in the organochlorine levels, including HCHs, between mothers who have eaten fish once a week and those who consumed fish more than once per week in Noushahr. PMID- 22047616 TI - Prediction of RNA Polymerase II recruitment, elongation and stalling from histone modification data. AB - BACKGROUND: Initiation and elongation of RNA polymerase II (RNAPII) transcription is regulated by both DNA sequence and chromatin signals. Recent breakthroughs make it possible to measure the chromatin state and activity of core promoters genome-wide, but dedicated computational strategies are needed to progress from descriptive annotation of data to quantitative, predictive models. RESULTS: Here, we describe a computational framework which with high accuracy can predict the locations of core promoters, the amount of recruited RNAPII at the promoter, the amount of elongating RNAPII in the gene body, the mRNA production originating from the promoter and finally also the stalling characteristics of RNAPII by considering both quantitative and spatial features of histone modifications around the transcription start site (TSS).As the model framework can also pinpoint the signals that are the most influential for prediction, it can be used to infer underlying regulatory biology. For example, we show that the H3K4 di- and tri- methylation signals are strongly predictive for promoter location while the acetylation marks H3K9 and H3K27 are highly important in estimating the promoter usage. All of these four marks are found to be necessary for recruitment of RNAPII but not sufficient for the elongation. We also show that the spatial distributions of histone marks are almost as predictive as the signal strength and that a set of histone marks immediately downstream of the TSS is highly predictive of RNAPII stalling. CONCLUSIONS: In this study we introduce a general framework to accurately predict the level of RNAPII recruitment, elongation, stalling and mRNA expression from chromatin signals. The versatility of the method also makes it ideally suited to investigate other genomic data. PMID- 22047618 TI - Biotic transformation of anticoccidials in soil using a lab-scale bio-reactor as a precursor-tool. AB - Two anticoccidial agents, salinomycin and robenidine, heavily used in the worldwide veterinary meat production, were investigated for their potential biotic degradation by cultured soil bacteria. The degradation-study was performed in lab-scale bio-reactors under aerobic and anaerobic conditions incubated for 200 h with a mixed culture of soil bacteria. Samples were analyzed by LC-MS/MS and potential transformation products were tentatively identified. Salinomycin was degraded under aerobic conditions and traces could be found after 200 h, however, seems more persistent under anaerobic conditions. Four transformation products of salinomycin were discovered. Robenidine was degraded under aerobic and anaerobic conditions, however, traces of robenidine were observed after 200 h. Five biotic transformation products of robenidine were discovered. PMID- 22047619 TI - High frequency of diastolic dysfunction in a population-based cohort of elderly women--but poor association with the symptom dyspnea. AB - BACKGROUND: The European Society of Cardiology recently proposed a new algorithm "How to diagnose heart failure with normal ejection fraction". Central element of the diagnostic strategy is the demonstration of diastolic dysfunction, either by tissue Doppler-derived indices in first line, or in second line by a combination of elevated blood levels of natriuretic peptide with abnormal tissue Doppler findings. We thought to use this diagnostic flowchart in a population-based cohort of elderly women, in whom the prevalence of diastolic dysfunction and heart failure is believed to be high. The purpose was to evaluate the association of dyspnea with the presence of diastolic dysfunction. METHODS: The study cohort recruited from a cross-sectional follow-up examination of the SALIA cohort (study on the influence of air pollution on lung function, inflammation, and aging). Participants with cardiac or pulmonary disease were excluded, 291 participants formed the final study group (all women, age range 69 to 79 years, all in sinus rhythm, LV ejection fraction > 50%, LV enddiastolic volume index < 97 mL/m2). Quality of life was assessed by the Minnesota living with heart failure questionnaire, and actual symptoms by a structural questionnaire; the examination consisted of a physical examination, measurement of B-type natriuretic peptide, ECG and tissue Doppler echocardiography. Diastolic dysfunction was assumed when the E/E' ratio exceeded 15 as derived from tissue Doppler. In case, tissue Doppler yielded an E/E' ratio ranging from 8 to 15, additional non-invasive parameters had to be fulfilled: left atrial volume index > 40 ml/m2 body surface, or left ventricular mass index > 122 g/m2 body surface, or transmitral E/A ratio < 0.5 plus deceleration time > 280 ms, or blood level of brain natriuretic peptide (BNP) > 200 pg/mL. RESULTS: The examinations were concordant with the presence of diastolic dysfunction in 122/291 participants (41.9%). The diagnosis based in 94% of cases on two criteria: in 50 cases on the criterion "E/E' ratio > 15", and in 65 cases on the criterion "15 > E/E'>8 and LV mass index > 122 g/m2". The participants with diastolic dysfunction had on average a higher body mass index, more frequent a history of arterial hypertension and of hospitalization for congestive heart failure, poorer quality of life, and higher BNP blood levels as compared to those participants without signs of diastolic dysfunction. The number of participants complaining exertional dyspnea, however, was similar distributed among the subgroups with and without signs of diastolic dysfunction (40.2 vs 40.8%; p = n.s). In a logistic regression model, the symptom dyspnea was best predicted by systolic pulmonary artery pressure, followed by left atrial volume index, BNP, and body mass index. CONCLUSION: The demonstration of diastolic dysfunction showed only a poor association with the symptom dyspnea in a cohort of elderly women with otherwise normal systolic function. Additional structural or hemodynamic changes are necessary to "explain" the symptom dyspnea. It is unclear whether these additional factors are secondary to a more advanced stage of diastolic dysfunction, or are related to cardiovascular co-morbidities, or both. PMID- 22047620 TI - Ferret islet amyloid polypeptide (IAPP): characterization of in vitro and in vivo amyloidogenicity. AB - Diabetes in the domestic ferret (Mustela putorius furo) has previously been described and the purpose of this study was to evaluate if the ferret could serve as a model for the study of beta-cell degeneration associated with formation of islet amyloid. The nucleotide and amino acid sequence of ferret islet amyloid polypeptide (IAPP) 1-37 was identified and the synthesized peptide was studied with regards to in vitro amyloidogenicity and potential cellular toxicity in a comparative approach to human, cat and the nonamyloidogenic rat IAPP. Ferret IAPP forms amyloid-like fibrils, but with a longer lag phase than human and cat IAPP and the aggregation process was shown to reduce cell viability of cultured beta cells, but with less potency than these two amyloidogenic counterparts. Immunohistochemistry of ferret pancreas confirmed IAPP expression in the islets of Langerhans, but no islet amyloid was found in a very limited sample size of one diabetic and five healthy ferrets. Islet amyloid has never been described in ferrets, and it is not possible to determine if it is due to lack of studies/material or to the fact that the ferret's life span is too short to present with such pathology. PMID- 22047621 TI - [The Act of Promotion of Personal Autonomy and Long-Term Care. Reflections and recommendations for better development]. AB - The present article provides a critical analysis of the state of affairs of the care of dependent individuals and proposals for reform of social protection systems for dependency - especially the Act of Promotion of Personal Autonomy and Long-Term Care. The existing form of public coverage is linked to the theory of public finance. Against this background, a series of recommendations are made to achieve the goals of this important component of the welfare state. PMID- 22047622 TI - Incidence of colorectal cancer and influence of dietary habits in fifteen European countries from 1971 to 2002. AB - OBJECTIVE: This study aimed to analyze the incidence of colorectal cancer in 15 European countries in recent decades and the relationship between the incidence found and changes in dietary habits. METHODS: Pearson's or Spearman's correlation coefficients were calculated by comparing incidence rates obtained from the International Agency for Research on Cancer for 1971-2002 with data on per capita consumption obtained from the Food and Agriculture Organization of the United Nations using 10-year delay intervals. RESULTS: Incidence rates increased in all countries except France in men and except Austria, Denmark, England and France in women. Of the dietary variables considered, there were marked increasing trends (linear regression coefficient, R >=0.5) in red meat consumption in Germany (R = 0.9), Austria (R = 0.7), Finland (R = 0.8), Italy (R = 0.9), Poland (R = 0.5), Spain (R = 2.1), Sweden (R = 0.6), and the Netherlands (R = 0.7). CONCLUSIONS: Changes in dietary habits may be consistent with the observed trends in the incidence of colorectal cancer in the distinct European countries. PMID- 22047623 TI - [Research in primary care as an area of knowledge. SESPAS Report 2012]. AB - Primary care offers huge potential for research. This setting is an area of knowledge that must expand to improve the quality of its services and patients' health. Population-based clinical studies with a focus on health promotion and primary, secondary and tertiary disease prevention offer unique research opportunities. Developing research in the biopsychosocial model of clinical practice and new models of integrated healthcare and community care is therefore a priority. The framework and activities carried out by the Research Network in Preventive Activities and Health Promotion have been instrumental in the development of research in primary care in Spain. Despite the efforts invested by various institutions, foundations, teaching and research departments in primary care research, the projected outputs in terms of volume, quality and impact have not been achieved. The involvement of primary care professionals in research platforms is insufficient, with scarce contribution toward investment in specific primary care research projects. To change the current status of research in primary care, a number of measures are required, namely, the consolidation of research organisms specific to primary care with adequate allocation of funding and staff, and the allocation of specific time for research to primary care professionals to enable them to produce significant projects and consolidate established research lines in their areas of expertise, with applications mainly in quality improvement and innovation of primary care services. PMID- 22047624 TI - [Attitudes toward online HIV/sexually-transmitted infection prevention programs and Internet user profiles among men who have sex with men]. AB - OBJECTIVES: To describe the attitudes of men who have sex with men (MSM) toward online HIV/sexually-transmitted infection (STI) prevention programs and to identify and characterize user profiles with regard to their attitudes toward online prevention programs. METHOD: A survey in gay venues or via the internet was completed by 2,044 participants from Madrid, Barcelona, Bilbao and San Sebastian (Spain). The survey explored socio-demographic variables, sexual behavior and other risk behaviors associated with HIV infection, as well as attitudes toward online prevention programs. The statistical analysis included factor analysis and non-hierarchical cluster analysis. RESULTS: Most MSM had positive attitudes towards online HIV/STI prevention programs. Factor analysis revealed two factors: online prevention aimed at interaction and online prevention aimed at information. Based on these factors, three user profiles were identified: users oriented toward informative and interactive online prevention (53.5%), users oriented toward interactive online prevention (25.9%) and users were not oriented toward online prevention (20.7%). On characterizing these profiles, we observed a significant presence of men who were not interested in online prevention among those with a lower educational level, bisexual men and HIV-positive men. Conversely, those most receptive to online prevention were men self-identified as gay, those with a bachelors degree, those who had been tested for HIV and those who were HIV-negative. CONCLUSION: The internet can facilitate sexual health promotion among MSM. Characterization of user profiles offers the possibility of segmenting prevention programs and of combining online and offline strategies. PMID- 22047625 TI - [Motivations for tobacco consumption among adolescents in an urban high school]. AB - OBJECTIVE: To determine the motivations (attitudes, beliefs and experiences) for tobacco consumption among adolescents. METHODS: This study was based on qualitative methodology using six 50-minute discussion groups with 6-8 adolescents per group during the 2008/09 school year. Purposive sampling was performed of 12-18 year-old adolescents attending a middle-class urban school (Jaen, Spain). The sample was stratified by educational level as the homogeneity criterion and gender and tobacco consumption as the heterogeneity criterion. Content analysis consisted of coding, triangulation of categories and obtaining and verifying the results. RESULTS: There were 44 adolescents (54% male). The participants reported that smoking relaxed and improved self-image, providing security (boys) and improving relations with the opposite sex, as well as weight control (girls). The family encouraged smoking by providing a model to imitate, although many adolescents hid their smoking from their families. Friends constituted a pressure group to start or continue smoking. Starting secondary school marked the beginning of experimental use. Society tended to accept consumption and buying tobacco was easy for minors. University students were a role model and were free to smoke. The adolescents looked to their parents and educators/health workers to provide a model of abstinence and reported that they were well informed but only remembered powerful messages. Participants unanimously indicated that tobacco causes addiction, but in proportion to the duration of consumption, and were concerned only with the immediate symptoms caused by smoking. Teenage smokers associated multiple drug use with leisure time. CONCLUSIONS: This study provides useful data on motivation that could be used to improve smoking prevention interventions among adolescents. The most important factors seem to be peer influence, parental attitudes, easy access to tobacco and symptoms of dependence. PMID- 22047626 TI - Oral ezatiostat HCl (Telintra(r), TLK199) and idiopathic chronic neutropenia (ICN): a case report of complete response of a patient with G-CSF resistant ICN following treatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1) inhibitor. AB - Idiopathic chronic neutropenia (ICN) describes a heterogeneous group of hematologic diseases characterized by low circulating neutrophil levels often associated with recurrent fevers, chronic mucosal inflammation, and severe systemic infections. The severity and risk of complications, including serious infections, are inversely proportional to the absolute neutrophil count (ANC), with the greatest problems occurring in patients with an ANC of less than 0.5 * 109/L. This case report describes a 64-year-old female with longstanding rheumatoid arthritis who subsequently developed ICN with frequent episodes of sepsis requiring hospitalization and prolonged courses of antibiotics over a 4 year period. She was treated with granulocyte colony stimulating factors (G-CSF) but had a delayed, highly variable, and volatile response. She was enrolled in a clinical trial evaluating the oral investigational agent ezatiostat. Ezatiostat, a glutathione S-transferase P1-1 inhibitor, activates Jun kinase, promoting the growth and maturation of hematopoietic progenitor stem cells. She responded by the end of the first month of treatment with stabilization of her ANC (despite tapering and then stopping G-CSF), clearing of fever, and healing of areas of infection. This ANC response to ezatiostat treatment has now been sustained for over 8 months and continues. These results suggest potential roles for ezatiostat in the treatment of patients with ICN who are not responsive to G-CSF, as an oral therapy alternative, or as an adjunct to G-CSF, and further studies are warranted. PMID- 22047627 TI - Understanding physicians' acceptance of the Medline system for practicing evidence-based medicine: a decomposed TPB model. AB - PURPOSE: Evidence-based medicine (EBM) supports physicians in their improvement of clinical quality and enhances hospitals' improvement of patient safety. Many health care institutions implement information systems to support physicians practicing EBM. However, studies exploring the antecedent factors of physicians' usage intention of information systems facilitating EBM practice are rare. Hence this study proposed a research model based on the decomposed theory of the planned behavior model (decomposed TPB) to investigate the factors influencing physicians' acceptance of the Medline system. METHODS: A field survey was conducted in Taiwan to collect data from physicians with experience in using the Medline system. A valid sample of 224 physicians was collected for data analysis. Structural equation modeling using the partial least squares (PLS) method with bootstrap estimate was used to test the research model. RESULTS: The findings of this study show that a physician's usage intention is significantly influenced by three factors, i.e. attitude, the subjective norm, and perceived behavior control. Furthermore, these three factors can be predicted by perceived usefulness and perceived ease of use, interpersonal influence, personal innovativeness in IT and self-efficacy, respectively. CONCLUSIONS: The results of this study indicate that our research model provides an effective prediction of the intention of physicians to use the Medline system and provides valuable implications for academics and practitioners. PMID- 22047628 TI - Induced oscillatory responses during the Sternberg's visual memory task in patients with Alzheimer's disease and mild cognitive impairment. AB - In this study we used magnetoencephalography during a modified version of the Sternberg's memory recognition task performed by patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI), and by age-matched healthy controls to identify differences in induced oscillatory responses. For analyses, we focused on the retention period of the working memory task. Multiple-source beamformer and Brain Voyager were used for localization of source-power changes across the cortex and for statistic group analyses, respectively. We found significant differences in oscillatory response during the task, specifically in beta and gamma frequency bands: patients with AD showed reduced beta event related desynchronization (ERD) in the right central area compared to controls, and reduced gamma ERD in the left prefrontal and medial parietal cortex compared to patients with MCI. Our findings suggest that reduced oscillatory responses over certain brain regions in high frequency bands (i.e., beta, gamma), and especially in the beta band that was significantly different between AD patients and healthy subjects, may represent brain electromagnetic changes underlying visual-object working memory dysfunction in early AD, and a neurophysiological indicator of cognitive decline. PMID- 22047629 TI - Polypeptide folding-mediated tuning of the optical and structural properties of gold nanoparticle assemblies. AB - Responsive hybrid nanomaterials with well-defined properties are of significant interest for the development of biosensors with additional applications in tissue engineering and drug delivery. Here, we present a detailed characterization using UV-vis spectroscopy and small angle X-ray scattering of a hybrid material comprised of polypeptide-decorated gold nanoparticles with highly controllable assembly properties. The assembly is triggered by a folding-dependent bridging of the particles mediated by the heteroassociation of immobilized helix-loop-helix polypeptides and a complementary nonlinear polypeptide present in solution. The polypeptides are de novo designed to associate and fold into a heterotrimeric complex comprised of two disulfide-linked four-helix bundles. The particles form structured assemblies with a highly defined interparticle gap (4.8+/-0.4 nm) that correlates to the size of the folded polypeptides. Transitions in particle aggregation dynamics, mass-fractal dimensions and ordering, as a function of particle size and the concentration of the bridging polypeptide, are observed; these have significant effects on the optical properties of the assemblies. The assembly and ordering of the particles are highly complex processes that are affected by a large number of variables including the number of polypeptides bridging the particles and the particle mobility within the aggregates. A fundamental understanding of these processes is of paramount interest for the development of novel hybrid nanomaterials with tunable structural and optical properties and for the optimization of nanoparticle-based colorimetric biodetection strategies. PMID- 22047630 TI - Expression of antimicrobial peptides in diabetic foot ulcer. AB - BACKGROUND: Foot ulcers are one of the main diabetes complications due to its high frequency and difficulty of complete healing. There are several factors that participate in diabetic ulcers development and limited information exists about the role of antimicrobial peptides (AMP) in its pathogenesis. OBJECTIVE: The aim of this study was to analyze the expression pattern of the main AMPs: Human Neutrophil Peptide (HNP)-1, Human beta-defensin (HBD)-1, HBD-2, HBD-3, HBD-4 and cathelicidin LL-37 in biopsies from diabetic foot ulcers (DFU). METHODS: 20 biopsies from DFU grade 3 according to Wagner's classification and 20 biopsies from healthy donors were obtained. Real time PCR, immunohistochemistry and primary cell cultures were performed. RESULTS: beta-Defensins were overexpressed in DFU, whereas LL-37 has low or none expression in comparison with healthy skin. When primary cell culture from these biopsies were performed and infected with Staphylococcus aureus, epidermal cell from diabetic ulcers showed lower LL-37 expression compared with cell cultures from healthy donors skin. CONCLUSION: These results suggest that though most AMPs are expressed in DFU, this production is not appropriate to promote wound healing and contain secondary infections. PMID- 22047631 TI - Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's Biomarkers Standardization Initiative. AB - BACKGROUND: Numerous studies show that the cerebrospinal fluid biomarkers total tau (T-tau), tau phosphorylated at threonine 181 (P-tau(181P)), and amyloid-beta (1-42) (Abeta(1-42)) have high diagnostic accuracy for Alzheimer's disease. Variability in concentrations for Abeta(1-42), T-tau, and P-tau(181P) drives the need for standardization. METHODS: Key issues were identified and discussed before the first meeting of the members of the Alzheimer's Biomarkers Standardization Initiative (ABSI). Subsequent ABSI consensus meetings focused on preanalytical issues. RESULTS: Consensus was reached on preanalytical issues such as the effects of fasting, different tube types, centrifugation, time and temperature before storage, storage temperature, repeated freeze/thaw cycles, and length of storage on concentrations of Abeta(1-42), T-tau, and P-tau(181P) in cerebrospinal fluid. CONCLUSIONS: The consensus reached on preanalytical issues and the recommendations put forward during the ABSI consensus meetings are presented in this paper. PMID- 22047632 TI - Is Alzheimer's disease amyloidosis the result of a repair mechanism gone astray? AB - Here, we synthesize several lines of evidence supporting the hypothesis that at least one function of amyloid-beta is to serve as a part of the acute response to brain hemodynamic disturbances intended to seal vascular leakage. Given the resilient and adhesive physicochemical properties of amyloid, an abluminal hemostatic repair system might be highly advantageous, if deployed on a limited and short-term basis, in young individuals. However, in the aged, inevitable cardiovascular dysfunction combined with brain microvascular lesions may yield global chronic hypoperfusion that may lead to continuous amyloid deposition and consequential negative effects on neuronal viability. A large body of experimental evidence supports the hypothesis of an amyloid-beta rescue function gone astray. Preventing or inducing the removal of amyloid in Alzheimer's disease (AD) has been simultaneously successful and disappointing. Amyloid deposits clearly play major roles in AD, but they may not represent the preeminent factor in dementia pathogenesis. Successful application of AD preventative approaches may hinge on an accurate and comprehensive view of comorbidities, including cardiovascular disease, diabetes, and head trauma. PMID- 22047633 TI - Effect of human cerebrospinal fluid sampling frequency on amyloid-beta levels. AB - BACKGROUND: beta-amyloid peptide (Abeta) is associated with neurodegeneration in Alzheimer's disease. Emerging evidence indicates that Abeta levels in cerebrospinal fluid (CSF) may serve as an early clinical biomarker for evaluating pharmacological activity of new drug candidates targeting Abeta production or Abeta clearance. Therefore, it is critical to understand whether intrasubject levels of CSF Abeta are consistent between sampling intervals to determine whether Abeta can be used as a pharmacodynamic biomarker for drug candidates. Previous studies have produced seemingly conflicting observations for the intrasubject stability of CSF Abeta levels; we attempt to reconcile these conflicting observations. METHODS: The current study examined the Abeta levels in CSF collected with various sampling frequencies from three clinical studies conducted in healthy young or elderly subjects at the same investigative site for the purpose of designing future studies. RESULTS: The results suggest that CSF sampling frequency and/or sampling volume contributes to intrasubject variability in CSF Abeta levels, and that lowering the CSF sampling frequency may help minimize this effect. CONCLUSION: These results will help guide clinical trial design for Alzheimer's disease therapy. PMID- 22047635 TI - Prognostic evaluation of tumour type and other histopathological characteristics in advanced epithelial ovarian cancer, treated with surgery and paclitaxel/carboplatin chemotherapy: cell type is the most useful prognostic factor. AB - AIM: Ovarian carcinomas have been classified into types I and II according to the hypothesised mode of carcinogenesis and molecular characteristics. The prognostic significance of this classification has not been studied. PATIENTS AND METHODS: Five hundred and sixty-eight patients with histologically confirmed, ovarian, fallopian tube or peritoneal carcinomas, international federation of gynecology and obstetrics (FIGO) stages IIC-IV, treated with paclitaxel/platinum following cytoreductive surgery, were included in this analysis. Type I included low-grade serous, mucinous, endometrioid and clear-cell and type II high-grade serous, unspecified adenocarcinomas and undifferentiated carcinomas. RESULTS: Median overall survival (OS) was 49 months for type I versus 45 for type II (p=0.576). In contrast to type II, there was considerable prognostic heterogeneity among the subtypes included in type I. Cox regression analysis showed that cell-type classification: low-grade serous, mucinous, endometrioid, clear-cell, type II (high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was an independent predictor of survival (respective median OS 121 versus 15 versus 64 versus 29 versus 45 months, p=0.003). On the contrary, histopathological subtype or tumour type (I versus II) did not offer additional prognostic information. CONCLUSION: The proposed model of ovarian tumourigenesis does not reflect tumour behaviour in advanced disease. Tumour-cell type is the most relevant histopathological prognostic factor in advanced ovarian cancer treated with platinum/paclitaxel. PMID- 22047636 TI - High prevalence of cervical squamous intraepithelial lesions in women on antiretroviral therapy in Cameroon: Is targeted screening feasible? AB - BACKGROUND: Cervical cancer is the most common cancer in women in low-income countries. Although cervical cancer incidence and mortality is higher in HIV positive women, resource limitations restrict the implementation of systematic screening programs in these women. We explored the potential for targeted screening by assessing the prevalence, severity and predictors of cervical squamous intra-epithelial lesions (SILs) in HIV-positive women in Cameroon. METHODS AND FINDINGS: We conducted a cross-sectional study of women on antiretroviral therapy in Cameroon. Socio-demographic, behavioral, and clinical information was obtained from eligible women. Cervical exfoliated cells were then collected, a conventional cytology performed and epithelial lesions classified according to the Bethesda 2001 system. A total of 282 women, aged 19-68 years, were enrolled in this study. The median CD4 count was 179 cells/microliter (interquartile range: 100-271). SILs were detected in 43.5% of the 276 women with satisfactory samples: including atypical squamous cells of unknown significance (ASCUS) 0.7%, low-grade SIL (LSIL) 25.0%, atypical squamous cells, cannot exclude high grade lesions (ASC-H) 14.5%, and high-grade SIL (HSIL) 3.3%. None of the demographic or clinical characteristics considered significantly predicted the presence of any SILs or the presence of severe lesions requiring colposcopy. CONCLUSION: The prevalence of SIL in women on antiretroviral therapy in Cameroon was high underscoring the need for screening and care in this population. In the absence of any accurate demographic or clinical predictor of SIL, targeted screening does not seem feasible. Alternative affordable screening options need to be explored. PMID- 22047634 TI - The Alzheimer's Disease Neuroimaging Initiative: a review of papers published since its inception. AB - The Alzheimer's Disease Neuroimaging Initiative (ADNI) is an ongoing, longitudinal, multicenter study designed to develop clinical, imaging, genetic, and biochemical biomarkers for the early detection and tracking of Alzheimer's disease (AD). The study aimed to enroll 400 subjects with early mild cognitive impairment (MCI), 200 subjects with early AD, and 200 normal control subjects; $67 million funding was provided by both the public and private sectors, including the National Institute on Aging, 13 pharmaceutical companies, and 2 foundations that provided support through the Foundation for the National Institutes of Health. This article reviews all papers published since the inception of the initiative and summarizes the results as of February 2011. The major accomplishments of ADNI have been as follows: (1) the development of standardized methods for clinical tests, magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers in a multicenter setting; (2) elucidation of the patterns and rates of change of imaging and CSF biomarker measurements in control subjects, MCI patients, and AD patients. CSF biomarkers are consistent with disease trajectories predicted by beta-amyloid cascade (Hardy, J Alzheimers Dis 2006;9(Suppl 3):151-3) and tau mediated neurodegeneration hypotheses for AD, whereas brain atrophy and hypometabolism levels show predicted patterns but exhibit differing rates of change depending on region and disease severity; (3) the assessment of alternative methods of diagnostic categorization. Currently, the best classifiers combine optimum features from multiple modalities, including MRI, [(18)F] fluorodeoxyglucose-PET, CSF biomarkers, and clinical tests; (4) the development of methods for the early detection of AD. CSF biomarkers, beta-amyloid 42 and tau, as well as amyloid PET may reflect the earliest steps in AD pathology in mildly symptomatic or even nonsymptomatic subjects, and are leading candidates for the detection of AD in its preclinical stages; (5) the improvement of clinical trial efficiency through the identification of subjects most likely to undergo imminent future clinical decline and the use of more sensitive outcome measures to reduce sample sizes. Baseline cognitive and/or MRI measures generally predicted future decline better than other modalities, whereas MRI measures of change were shown to be the most efficient outcome measures; (6) the confirmation of the AD risk loci CLU, CR1, and PICALM and the identification of novel candidate risk loci; (7) worldwide impact through the establishment of ADNI-like programs in Europe, Asia, and Australia; (8) understanding the biology and pathobiology of normal aging, MCI, and AD through integration of ADNI biomarker data with clinical data from ADNI to stimulate research that will resolve controversies about competing hypotheses on the etiopathogenesis of AD, thereby advancing efforts to find disease-modifying drugs for AD; and (9) the establishment of infrastructure to allow sharing of all raw and processed data without embargo to interested scientific investigators throughout the world. The ADNI study was extended by a 2-year Grand Opportunities grant in 2009 and a renewal of ADNI (ADNI-2) in October 2010 through to 2016, with enrollment of an additional 550 participants. PMID- 22047637 TI - The impact of significant others in motivational enhancement therapy: findings from project MATCH. AB - BACKGROUND: Social network support for abstinence has been associated with improved treatment outcomes among samples of individuals with alcohol use disorders. As a result, research studies have focused on the inclusion of significant others (SOs) in the treatment process. Nonetheless, little is known about 1) the specific influence SOs may have on clients during treatment sessions or 2) whether SO within-session behaviors have any relationship to client post treatment drinking. METHOD: In the current study, Motivational Enhancement Therapy sessions in which a SO was present were coded using a behavioral coding system designed to measure SO and client within-session language. RESULTS: Relationships were observed between SO and client within-session language. Furthermore, some specific SO categories of language predicted post-treatment client drinking. CONCLUSIONS: This study is the first systematic evaluation of SO contributions in substance abuse treatment sessions. Future research examining SO language in the treatment of alcohol use disorders might allow clinicians to avoid contributions from SOs that are associated with poorer drinking outcomes. PMID- 22047638 TI - Differential accumulation of BPA in some tissues of offspring of Balb-C mice exposed to different BPA doses. AB - Pregnant adult Balb-C mice were exposed daily to two different doses of Bisphenol A (BPA) by subcutaneous injection beginning on gestational day 1 through the seventh day after delivery. The mothers were sacrificed on postpartum day 21, and the offspring were sacrificed at 3 months of age. Control mice were subjected to the same experimental protocol but received saline injections. The liver, muscles, hindbrain and forebrain of the offspring were dissected and processed using HPLC to assess the level of BPA in the tissues and to determine its dependence on the exposure dose and gender. For comparison, the same tissues were dissected from the mothers and analysed. We report the following results: (1) the level of BPA that accumulated in a given tissue was dependent on the exposure dose; (2) the rank order of BPA accumulation in the various tissues was dependent on the gender of the offspring; (3) the average BPA concentrations in the liver and muscle of the female offspring were higher than in the males; and (4) the average BPA concentration in the central nervous system (i.e., the hindbrain and forebrain) of the male offspring was higher than in the females. PMID- 22047639 TI - Determination of pyrimidine and purine bases by reversed-phase capillary liquid chromatography with at-line surface-enhanced Raman spectroscopic detection employing a novel SERS substrate based on ZnS/CdSe silver-quantum dots. AB - We have developed a new SERS substrate based on the reduction of silver nitrate in the presence of ZnS-capped CdSe quantum dots. This substrate showed higher sensitivities as compared to a hydroxylamine-reduced silver sol. On the basis of this new substrate, at-line SERS detection was coupled with capillary liquid chromatography (cap-LC) for the separation and selective determination of pyrimidine and purine bases. For this purpose, wells of a dedicated microtiter plate were loaded with 20 MUL of the SERS substrate and placed on an automated x,y translation stage. A flow-through microdispenser capable of ejecting 50 pL droplets, at a frequency 100 Hz, was used as the interface to connect the cap-LC system to the wells loaded with SERS substrate. A detailed study of the dependence of both the separation and the surface-enhanced Raman spectra of each base on the pH was performed to optimize the system for maximum sensitivity and selectivity. Highly satisfactory analytical figures of merit were obtained for the six investigated bases (cytosine, xanthine, hypoxanthine, guanine, thymine, and adenine) with detection limits ranging between 0.2 and 0.3 ng injected on the capillary LC column, and the precisions were in the range of 3.0-6.3%. PMID- 22047640 TI - Initiation but no execution - modulation of peripheral blood lymphocyte apoptosis in rheumatoid arthritis - a potential role for heat shock protein 70. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which causes synovial damage. Persistence of lymphocyte infiltrates in the rheumatoid synovium has been attributed to abnormal apoptosis. While not comprehensively investigated, perturbations in peripheral blood lymphocyte (PBL) apoptosis may also be involved in perpetuation of autoimmune processes in RA. METHODS: We investigated total, CD4+ and CD19+ PBL apoptosis in our study cohort by monitoring the translocation of phosphatidylserine using the Annexin-V assay. To examine the role of death receptor mediated apoptosis as well as activation induced-cell-death (AICD), PBLs were labeled with CD95/Fas and CD69 markers and enumerated by flow cytometry. Proteolytic activity of initiator and executioner caspases was determined by luminometry. DNA fragmentation assays were used to examine whether apoptotic signals were transduced to the nucleus. Quantitative PCR arrays were used to investigate apoptotic pathways associated with RA-PBLs. Since heat-shock-protein-70 (HSP70) is an inducible protein which modulates apoptotic signals, we determined HSP70 levels by intra-cellular flow cytometry and western blots. RESULTS: The RA-PBLs showed signs of elevated apoptosis whilst in circulation. These include increases in the loss of plasma membrane asymmetry, indicated by increased externalization of phosphatidylserine (especially in B lymphocytes). RA-PBLs showed a bias to CD95/Fas mediated apoptotic pathways, but low levels of the CD69 marker suggested that this was not associated with immune activation. Although downstream markers of apoptosis such as caspase-3/7 activity, were increased, no DNA fragmentation was observed in RA-PBLs. Interestingly, elevated levels of apoptosis did not correlate with absolute lymphocyte counts in RA patients. Levels of HSP70 were highly elevated in RA-PBLs compared to controls. CONCLUSION: The results suggest that while apoptosis may be initiated in RA-PBLs, they may lack commitment to fully executing the apoptotic program. This may be related to inhibition on apoptotic transduction by HSP70. This study provides evidence that abnormalities in RA-PBLs apoptosis may occur whilst still in circulation and may contribute to pathogenesis of the disease. PMID- 22047641 TI - Receptor-mediated endocytosis of nanoparticles of various shapes. AB - Cellular uptake through endocytosis is crucial for drug delivery and nanomedicine. However, the conditions under which passive endocytosis (i.e., not ATP driven) takes place are not well understood. We report MD simulations of the passive uptake of ligand-coated nanoparticles with varying size, shape, coverage, and membrane-binding strength. We find that the efficiency of passive endocytosis is higher for spherocylindrical particles than for spheres and that endocytosis is suppressed for particles with sharp edges. PMID- 22047642 TI - Synthesis, X-ray structure and cytotoxic effect of nickel(II) complexes with pyrazole ligands. AB - Here we present the synthesis of the new Ni(II) complexes with chelating ligands 1-benzothiazol-2-yl-3,5-dimethyl-1H-pyrazole (a), 5-(2-hydroxyphenyl)-3-methyl-1 (2-pyridylo)-1H-pyrazole-4-carboxylic acid methyl ester (b) and 1-benzothiazol-2 yl-5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (c). These ligands a-c create solid complexes with Ni(II). The crystal and molecular structures of two complexes were determined by X-ray diffraction method. Thermal stability of two complexes with ligand c by TG/DTG and DSC methods were also shown. Cytotoxic activity of all the complexes against three tumour cell lines and to normal endothelial cells (HUVEC) was also estimated. Complexes with ligand c exhibited relatively high cytotoxic activity towards HL-60 and NALM-6 leukaemia cells and WM-115 melanoma cells. Cytotoxic effectiveness of one of these complexes against melanoma WM-115 cells was two times higher than that of cisplatin. The protonation constant log K=9.63 of ligand b corresponding to the phenol 2-hydroxy group has been determined in 10% (v/v) DMSO/water solution (25 degrees C). The coordination modes (formation of two monomeric species: NiL and NiL(2)) in the complexes with Ni(II) are discussed for b on the basis of the potentiometric and UV/Vis data. PMID- 22047643 TI - Total synthesis and bioactivity of the marine alkaloid pityriacitrin and some of its derivatives. AB - We report herein the chemical synthesis and biological evaluation of beta carboline alkaloid pityriacitrin and some of its new derivatives. Using tryptophan or 5-hydroxytryptophan and 5-substituted indole-3-glyoxals as the starting materials, pityriacitrin and some of its derivatives were synthesized via the acid-catalyzed Pictet-Spengler reaction and fully characterized by (1)H and (13)C NMR, mass spectroscopy and IR determinations. Biological studies revealed that pityriacitrin has a weak antiproliferative activity against a panel of breast and prostate cancer cell lines, whereas some of its derivatives exhibited stronger and potent activity, which was associated with induction of both cell apoptosis and necrosis. PMID- 22047644 TI - Cyclin kinase subunit 1B nuclear expression predicts an adverse outcome for patients with relapsed/refractory multiple myeloma treated with bortezomib. AB - Amplification of cyclin kinase subunit 1B gene on chromosome 1q21 resulting in overexpression of cyclin kinase subunit 1B has been associated with disease progression in multiple myeloma. Bortezomib is a proteasome inhibitor that induces apoptosis in various cancer cells and has been shown to be effective as a salvage therapy for relapsed/refractory multiple myeloma. Our group has recently reported the adverse effect of 1q21 gains in relapsed and refractory multiple myeloma treated with bortezomib. However, whether nuclear cyclin kinase subunit 1B protein expression correlates with 1q21 gains and has prognostic value in patients with multiple myeloma receiving bortezomib regimen remains unclear. We, therefore, evaluated the nuclear expression of cyclin kinase subunit 1B protein in patients with relapsed/refractory multiple myeloma undergoing bortezomib therapy by immunohistochemistry. The 1q21 amplification status of the same cohort was examined by interphase cytoplasmic immunoglobulin fluorescence in situ hybridization. Of 60 cases, 19 (32%) were positive for cyclin kinase subunit 1B nuclear expression by immunohistochemistry. Seventeen (89%) of the immunohistochemistry-positive cases had 1q21 gain detected by cytoplasmic immunoglobulin fluorescence in situ hybridization, and 17 (77%) of the 22 cases with 1q21 gain showed increased cyclin kinase subunit 1B protein expression. cyclin kinase subunit 1B expression and 1q21 gain were strongly correlated (P < .0001). There was no significant difference in response rate between patients with and without cyclin kinase subunit 1B nuclear expression. However, patients with cyclin kinase subunit 1B expression had a significantly shorter progression free survival (1.9 versus 5.6 months; P < .0001) and overall survival (4.9 versus 22.4 months; P = .012) compared with those without cyclin kinase subunit 1B expression. Our results indicated that cyclin kinase subunit 1B nuclear expression detected by immunohistochemistry is an adverse prognostic factor for patients with multiple myeloma treated with bortezomib therapy. PMID- 22047645 TI - Sarcoidosis does not belong to or overlap with immunoglobulin G4-related diseases based on an assessment of serum immunoglobulin G4 levels in cardiac and noncardiac sarcoidosis. AB - Although sarcoidosis may exhibit histopathologic features similar to those of a newly emerging clinical entity, immunoglobulin G4-related sclerosing disease, sarcoidosis is currently not considered to be associated with immunoglobulin G4 related immunoinflammation. Not many studies on this association have been reported. We investigated serum immunoglobulin G4 levels among patients with sarcoidosis with or without cardiac involvement (cardiac sarcoidosis and non cardiac sarcoidosis patients). The mean serum immunoglobulin G4 level among the 65 patients with sarcoidosis was 56.8 +/- 43.0 mg/dL, which did not significantly differ between patients with cardiac sarcoidosis (54 +/- 48 mg/dL, n = 12) and patients without cardiac sarcoidosis (58 +/- 42 mg/dL; n = 53). Serum level of soluble interleukin 2 receptor, a potent marker that may reflect sarcoidosis activity, was elevated in cardiac sarcoidosis (910 +/- 683 U/L) and noncardiac sarcoidosis (689 +/- 399 U/L) but did not significantly differ between the groups. Immunohistochemistry of cardiac or lymph node specimens from patients with cardiac sarcoidosis showed only sparse or no infiltration of immunoglobulin G4-positive lymphocytes, in contrast to the moderate to severe infiltration of CD68-positive macrophages and CD45-positive lymphocytes. Although the number of study subjects was small, these findings collectively suggest that regardless of the presence or absence of cardiac involvement, sarcoidosis does not belong to or overlap with immunoglobulin G4-related sclerosing disease. PMID- 22047646 TI - The presence and location of epithelial implants and implants with epithelial proliferation may predict a higher risk of recurrence in serous borderline ovarian tumors: a clinicopathologic study of 188 cases. AB - Serous borderline ovarian tumors have a favorable prognosis, and recurrences are uncommon. The factors influencing recurrence are not fully understood. Epithelial inclusions are identified in serous borderline ovarian tumors and are traditionally referred to as epithelial implants, which often show epithelial proliferation. We investigated whether the presence of epithelial implant and epithelial proliferation portends a higher risk for recurrence of serous borderline ovarian tumors in patients who underwent surgical removal of these tumors. Also examined was whether the anatomical site of epithelial implant and epithelial proliferation was associated with a higher risk of recurrence. One hundred eighty-eight cases of pure serous or predominantly serous borderline ovarian tumors were studied for the presence of epithelial implant and epithelial proliferation, and subsequent recurrences were recorded. The anatomical sites of epithelial implant and epithelial proliferation were compared between serous borderline ovarian tumors with or without recurrence. Statistical analysis was performed using the chi(2) test. Epithelial implant was noted in 106 cases (56%), and epithelial proliferation, in 26 cases (14%). Recurrence was identified in 10.4% cases with epithelial implant and 23% cases with epithelial proliferation. Statistical analyses of patients with recurrence showed significant differences in the following groups: epithelial implant versus no epithelial implant (P < .025) and epithelial proliferation versus no epithelial implant (P < .001). Recurrence rates were higher in the epithelial implant and epithelial proliferation groups as compared with no epithelial implant or epithelial proliferation groups. Epithelial implant and epithelial proliferation appear to pose a statistically significantly higher risk of recurrence in serous borderline ovarian tumors as compared with the absence of epithelial implant. Although the anatomical location of such implants was not significantly associated with a higher risk, the presence of epithelial proliferation at multiple sites was more frequently seen in recurrent serous borderline ovarian tumors. PMID- 22047647 TI - Expression of endothelin 2 and localized clear cell renal cell carcinoma. AB - Despite the rising incidence of clear cell renal cell carcinoma, the molecular events that support its development and progression remain unclear. Herein, we evaluate the association of endothelin 2 expression with both clear cell renal cell carcinoma development and progression-free survival. We conducted real-time polymerase chain reaction to determine endothelin 2 expression levels on 238 patients who underwent nephrectomy for localized clear cell renal cell carcinoma, 161 of whom also had adjacent normal kidney samples available for analysis. To evaluate associations with clear cell renal cell carcinoma development, linear mixed models were used to compare differential expression between tumor and a normal kidney as well as to explore interactions with clinicopathologic features. To evaluate associations with prognosis, Cox proportional hazards models were used to assess the association of progression-free survival and endothelin 2 expression in tumor tissue. Overall, endothelin 2 expression was higher in tumor samples versus patient-matched normal kidney samples, with an average fold change of 1.99 (95% confidence interval, 1.48-2.60; P < .0001). This overexpression in tumor versus normal kidney samples was more pronounced in low- compared with high grade tumors (interaction, P = .0002), in early- compared with late-stage tumors (interaction, P = .001), and in tumors without compared with those with necrosis (interaction, P = .001). Moreover, an increasing endothelin 2 expression in tumors was associated with a longer progression-free survival (hazard ratio, 0.89; 95% confidence interval, 0.80-0.99; P = .03); however, after controlling for known clinicopathologic factors, this association was attenuated (hazard ratio, 0.99; 95% confidence interval, 0.89-1.09; P = .7). Up-regulation of endothelin 2 is a common and early event in localized clear cell renal cell carcinoma. Higher tumor expression of endothelin 2 is associated with a longer progression-free survival but not after adjustment for well-known pathologic indices. Thus, although endothelin 2 does not appear to be an independent prognostic marker, there is evidence of a putative role in clear cell renal cell carcinoma progression. If supportive mechanistic data can be produced, endothelin 2 could represent a potential target for chemopreventive or neoadjuvant therapeutics for clear cell renal cell carcinoma. PMID- 22047648 TI - Implementing clinical trials on an international platform: challenges and perspectives. AB - The importance of conducting medical research on a global or international platform cannot be overemphasized in current times. Sponsors are encouraging international clinical trials for a number of reasons. Globally, clinical trials are under increasing pressure to meet patient recruitment goals quickly and efficiently, at times with very limited resources. Conducting clinical trials in multiple countries increases access to potentially eligible study subjects. It is reasonable to believe that international trials will be completed more quickly and efficiently, leading to more rapid advancement in science and conservation of research-specific resources. Rapid advancement in science can reduce the burden of disease, promote health, and extend longevity for all people. In addition, generalizability, one of the major goals of translational medicine, will increase when recruiting patients from multiple countries and multiple ethnicities. Further, improvement of global health may be possible when certain types of clinical trials are conducted in countries that would not otherwise have access to an innovative drug or intervention. PMID- 22047649 TI - Surgical treatment of brain metastasis: a review. AB - Brain metastasis is the most common intracranial tumor in adults. Currently, treatment of brain metastasis requires multidisciplinary approach tailored for each individual patient. Surgery has an indispensible role in relieving intracranial mass effect, improving neurological status and survival while providing or confirming neuropathological diagnosis with low mortality and morbidity rates. Besides the resection of a single brain metastasis in patients with accessible lesions, good functional status, and absent/controlled extracranial disease; surgery is proven to play a role in management of multiple metastases. Surgical technique has an impact on the outcome since piecemeal resection rather than en bloc resection and leaving infiltrative zone behind around resection cavity may have a negative influence on local control. Best local control of brain metastasis can be accomplished with optimal surgical resection involving current armamentarium of preoperative structural and functional imaging, intraoperative neuromonitoring, and advanced microneurosurgical techniques; followed by adjunct therapies like stereotactic radiosurgery, whole brain radiotherapy, or intracavitary therapies. Here, treatment options for brain metastasis are discussed with controversies about surgery. PMID- 22047650 TI - CNS lymphoma masquerading as hemorrhagic stroke. PMID- 22047651 TI - Anti-NMDAR encephalitis in small-cell lung cancer: a case report. PMID- 22047652 TI - Anxiety sensitivity and breath-holding duration in relation to PTSD symptom severity among trauma exposed adults. AB - The present investigation examined the main and interactive effects of anxiety sensitivity and behavioral distress tolerance, indexed using the breath-holding task, in relation to PTSD symptom severity among trauma-exposed adults. Participants were 88 adults (63.6% women; M(age)=22.9, SD=9.1, range=18-62), recruited from the community, who met DSM-IV-TR PTSD Criterion A for lifetime trauma exposure. Covariates included number of potentially traumatic events, nonclinical panic attack history, and participant sex. Anxiety sensitivity was significantly incrementally associated with PTSD total symptom severity, as well as Avoidance and Hyperarousal symptom severity (p's<.01). Breath-holding duration was not significantly related to PTSD symptom severity (p's>.05). However, breath holding duration emerged as a significant moderator of the association between anxiety sensitivity and PTSD Avoidance symptom severity, such that lower breath holding duration exacerbated the effect of heightened anxiety sensitivity with regard to PTSD Avoidance symptom severity. PMID- 22047653 TI - Marginal benefit incidence of public health spending: evidence from Indonesian sub-national data. AB - We examine the marginal effects of decentralized public health spending by incorporating estimates of behavioural responses to changes in health spending in benefit incidence analysis. The analysis is based on a panel dataset of 207 Indonesian districts over the period from 2001 to 2004. We show that district public health spending is largely driven by central government transfers, with an elasticity of around 0.9. We find a positive effect of public health spending on utilization of outpatient care in the public sector for the poorest two quartiles. We find no evidence that public expenditures crowd out utilization of private services or household health spending. Our analysis suggests that increased public health spending improves targeting to the poor, as behavioural changes in public health care utilization are pro-poor. Nonetheless, most of the benefits of the additional spending accrued to existing users of services, as initial utilization shares outweigh the behavioural responses. PMID- 22047654 TI - Bacterial community structure and enzyme activities in a membrane bioreactor (MBR) using pure oxygen as an aeration source. AB - A pilot-scale membrane bioreactor was used to treat urban wastewater using pure oxygen instead of air as a source of aeration, to study its influence on bacterial diversity and levels of enzyme activities (acid and alkaline phosphatases, glucosidase, protease, and esterase) in the sludge. The experimental work was developed in two stages influenced by seasonal temperature. Operational parameters (temperature, pH, BOD5, COD, total and volatile suspended solids) were daily monitored, and enzyme activities measured twice a week. Redundancy analysis (RDA) was used to reveal relationships between the level of enzyme activities and the variation of operational parameters, demonstrating a significant effect of temperature and volatile suspended solids. Bacterial diversity was analyzed by temperature-gradient gel electrophoresis of PCR amplified partial 16S rRNA genes. Significant differences in community structure were observed between both stages. Sequence analysis revealed that the prevalent Bacteria populations were evolutively close to Alphaproteobacteria (44%), Betaproteobacteria (25%) and Firmicutes (17%). PMID- 22047655 TI - Low temperature thermo-chemical pretreatment of dairy waste activated sludge for anaerobic digestion process. AB - An investigation into the influence of low temperature thermo-chemical pretreatment on sludge reduction in a semi-continuous anaerobic reactor was performed. Firstly, effect of sludge pretreatment was evaluated by COD solubilization, suspended solids reduction and biogas production. At optimized condition (60 degrees C with pH 12), COD solubilization, suspended solids, reduction and biogas production was 23%, 22% and 51% higher than the control, respectively. Secondly, semi-continuous process performance was studied in a lab scale semi-continuous anaerobic reactor (5 L), with 4 L working volume. With three operated SRTs, the SRT of 15 days was found to be most appropriate for economic operation of the reactor. Combining pretreatment with anaerobic digestion led to 80.5%, 117% and 90.4% of TS, SS and VS reduction respectively, with an improvement of 103% in biogas production. Thus, low temperature thermo chemical can play an important role in reducing sludge production. PMID- 22047656 TI - Production and characterization of biopolyols and polyurethane foams from crude glycerol based liquefaction of soybean straw. AB - The feasibility of using crude glycerol to liquefy soybean straw for the production of biopolyols and polyurethane (PU) foams was investigated in this study. Liquefaction conditions of 240 degrees C, >180 min, 3% sulfuric acid loading, and 10-15% biomass loading were preferred for the production of biopolyols with promising material properties. Biopolyols produced under preferential conditions showed hydroxyl numbers from 440 to 540 mg KOH/g, acid numbers below 5 mg KOH/g, and viscosities from 16 to 45 Pa.s. PU foams produced under preferential conditions showed densities from 0.033 to 0.037 g/cm3 and compressive strength from 148 to 227 kPa. These results suggest that crude glycerol can be used as an alternative solvent for the liquefaction of lignocellulosic biomass such as soybean straw for the production of biopolyols and PU foams. The produced biopolyols and PU foams showed material properties comparable to their analogs from petroleum solvent based liquefaction processes. PMID- 22047657 TI - Effects of nitrate on methane production, fermentation, and microbial populations in in vitro ruminal cultures. AB - The objective of this study was to examine the effects of nitrate on methane production, important fermentation characteristics, Fibrobacter succinogenes, Ruminococcus albus, Ruminococcus flavefaciens, total bacteria, and methanogens using in vitro ruminal cultures. Potential adaptation of the above microbes and persistency of nitrate to mitigate CH4 production were also evaluated. Methane production was reduced by 70% at 12 MUmol ml(-1) and nearly completely at >=24 MUmol ml(-1) nitrate. Production of volatile fatty acids (VFAs) was affected to different extents at different nitrate concentrations. Over a series of six consecutive cultures receiving 12 MUmol ml(-1) nitrate, production of CH4 and VFA did not change significantly. R. albus and R. flavefaciens seemed to adapt to nitrate, while F. succinogenes and methanogens did not. Nitrate may be used in achieving persistent mitigation of CH4 production by ruminants. PMID- 22047658 TI - Improved volatile fatty acids production from proteins of sewage sludge with anthraquinone-2,6-disulfonate (AQDS) under anaerobic condition. AB - Organic matters in sewage sludge can be converted into volatile fatty acids (VFAs) as renewable carbon sources. This work for the first time applied anthraquinone-2,6-disulfonate (AQDS) for enhancing VFA production from sewage sludge. With 0.066 or 0.33 g AQDS g(-1) dried solids (DS), the yields for VFAs peak at 403 or 563 mg l(-1), 1.9- or 2.7-fold to the control. The accumulated VFAs were principally composed of acetate and propionate. The AQDS enhances degradation rates of model proteins (bovine serum albumin), but had little enhancement on that of model polysaccharides (dextrans). The acidification step is proposed the rate-limiting step for VFA production from sewage sludge, in which the AQDS molecules shuttle electrons to accelerate the redox reactions associated with amino acid degradation. Methanogenic activities are inhibited in the presence of AQDS. The AQDS-assisted VFAs are renewable organic carbon sources, although their direct use for anaerobic digestion is not advised. PMID- 22047659 TI - Preparation of levoglucosenone through sulfuric acid promoted pyrolysis of bagasse at low temperature. AB - Fast pyrolysis of bagasse pretreated by sulfuric acid was conducted in a fixed bed reactor to prepare levoglucosenone (LGO), a very important anhydrosugar for organic synthesis. The liquid yield and LGO yield were studied at temperatures from 240 to 350 degrees C and sulfuric acid loadings from 0.92 to 7.10 wt.%. An optimal LGO yield of 7.58 wt.% was obtained at 270 degrees C with a sulfuric acid pretreatment concentration of 0.05 M (corresponding to 4.28 wt.% sulfuric acid loading). For comparison, microcrystalline cellulose pretreated by 0.05 M sulfuric acid solution was pyrolyzed at temperature from 270 degrees C to 320 degrees C, and bagasse loaded with 3-5 wt.% phosphoric acid was pyrolyzed at temperature from 270 degrees C to 350 degrees C. The highest yield of LGO from bagasse was 30% higher than that from microcrystalline cellulose, and treatment with sulfuric acid allowed a 21% higher yield than treatment with phosphoric acid. PMID- 22047660 TI - The lignin present in steam pretreated softwood binds enzymes and limits cellulose accessibility. AB - The influence of cellulose accessibility and protein loading on the efficiency of enzymatic hydrolysis of steam pretreated Douglas-fir was assessed. It was apparent that the lignin component significantly influences the swelling/accessibility of cellulose as at low protein loadings (5FPU/g cellulose), only 16% of the cellulose present in the steam pretreated softwood was hydrolyzed while almost complete hydrolysis was achieved with the delignified substrate. When lignin (isolated from steam pretreated Douglas-fir) was added back in the same proportions it was originally found to the highly accessible and swollen, delignified steam pretreated softwood and to a cellulose control such as Avicel, the hydrolysis yields decreased by 9 and 46%, respectively. However, when higher enzyme loadings were employed, the greater availability of the enzyme could overcome the limitations imposed by both the lignin's restrictions on cellulose accessibility and direct binding of the enzymes, resulting in a near complete hydrolysis of the cellulose. PMID- 22047661 TI - Enhanced enzymatic saccharification of kenaf powder after ultrasonic pretreatment in ionic liquids at room temperature. AB - This study demonstrates for the first time that the enzymatic hydrolysis of cellulose is drastically enhanced following ultrasonic pretreatment of lignocellulosic material in ionic liquids (ILs) when compared to conventional thermal pretreatment. Five types of ILs, 1-buthyl-3-methylimidazolium chloride (BmimCl), 1-allyl-3-methylimidazolium chloride (AmimCl), 1-ethyl-3 methylimidazolium chloride (EmimCl), 1-ethyl-3-methylimidazolium diethyl phosphate (EmimDep), and 1-ethyl-3-methylimidazolium acetate (EmimOAc) were tested. Cellulose saccharification ratio was about 20% for kenaf powders pretreated in BmimCl, AmimCl, EmimCl, and EmimDep by conventional heating at 110 degrees C for 120 min. Conversely, 60-95% of cellulose was hydrolyzed to glucose, subsequent to ultrasonic pretreatment in the same ILs for 120 min at 25 degrees C. The cellulose saccharification ratio of kenaf powder in EmimOAc was 86% after only 15 min of the ultrasonic pretreatment at 25 degrees C, compared to only 47% in that case of thermal pretreatment in the IL. PMID- 22047662 TI - Characterization of Phragmites cummunis rhizosphere bacterial communities and metabolic products during the two stage sequential treatment of post methanated distillery effluent by bacteria and wetland plants. AB - This study deals with the characterization of rhizosphere bacterial communities and metabolic products produced during the two stage sequential treatment of post methanated distillery effluent by bacteria and constructed wetland plants. Results showed that bacterial treatment followed by wetland plants (Phragmites cummunis) resulted 94.5% and 96.0% reduction in BOD and COD values, respectively. The PCR-RFLP analysis showed the presence of Stenotrophomonas, Enterobacter, Pantoea, Acinetobacter and Klebsiella sp., as dominant rhizosphere bacterial communities which play an important role in degradation and decolorization of PMDE in wetland treatment system. Further, the LC-MS-MS and other spectrophotometric analysis have shown that most of the pollutants detected in untreated PMDE were diminished from bacteria and wetland plant treated PMDE indicating that bacteria and wetland plant rhizosphere microbes utilized them as carbon, nitrogen and energy source. While, methylbenzene, furfuryl alcohol, and 4 vinyl-2-methoxyphenol were detected as metabolites in bacteria and hexadecanol in wetland plant rhizosphere treated PMDE. PMID- 22047663 TI - Prognostic value of beta-human chorionic gonadotropin is dependent on day of embryo transfer during in vitro fertilization. AB - OBJECTIVE: To determine threshold beta-hCG levels predictive of an ongoing pregnancy (OP), live birth (LB), and multiple gestation (MG) in IVF cycles resulting from day-3 (D3) vs. day-5 (D5) embryo transfers (ET), to compare IVF cycle characteristics and pregnancy outcomes in D3 vs. D5 ET groups, and to assess the degree to which maternal characteristics and cycle parameters were predictive of higher beta-hCG levels. DESIGN: Retrospective analysis. SETTING: Infertility center. PATIENT(S): Women who had ET performed for IVF cycles between July 2004 and January 2010. INTERVENTION(S): Embryo transfer performed on either D3 or D5 after oocyte fertilization. MAIN OUTCOME MEASURE(S): Beta-hCG on day 15 after oocyte fertilization. RESULT(S): Beta-hCG levels were significantly higher with D5 ET compared with D3 ETs (D3: 103.6 +/- 4.4 IU/L vs. D5: 198.0 +/- 10.6 IU/L), and a multivariate analysis demonstrated that D5 ET was a significant predictor of higher beta-hCG levels. The beta-hCG thresholds predictive of OP were 78 IU/L and 160 IU/L for D3 and D5 ET, which predicted OP in 96% and 91% of cases, respectively. Similarly, for LB, the beta-hCG thresholds were 94 IU/L (79% positive predictive value [PPV]) and 160 IU/L (88% PPV), and for MG were 250 IU/L (18% PPV) and 316 IU/L (34% PPV), respectively. CONCLUSION(S): Initial beta-hCG levels are dependent on the day of ET and are a reliable and highly predictive tool for OP outcomes. PMID- 22047664 TI - Intrauterine injection of human chorionic gonadotropin before embryo transfer significantly improves the implantation and pregnancy rates in in vitro fertilization/intracytoplasmic sperm injection: a prospective randomized study. AB - OBJECTIVE: To investigate the value of intrauterine injection of human chorionic gonadotropin (hCG) before embryo transfer (ET). DESIGN: Prospective randomized study. SETTING: The Egyptian IVF-ET Center. PATIENT(S): Infertility patients younger than 40 years undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI). INTERVENTION(S): The study group (n = 167) received either 100 IU of hCG (n = 83), or 200 IU of hCG (n = 84) via intrauterine administration before ET. The control group (n = 93) underwent ET without hCG. After the interim analysis, the modified study group (n = 107) received intrauterine injection of 500 IU of hCG, and the control group (n = 105) underwent ET without hCG. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR) and implantation rate (IR). RESULT(S): The IR and PR were statistically significantly higher in the 500 hCG group (41.6% and 75%, respectively) as compared with the control group (29.5% and 60%, respectively). The IR and PR were 26.6% and 54% in the 100 hCG group, 28.3% and 57% in the 200 IU hCG group, and 29.4% and 60% in the control group, respectively, with no statistically significant difference. CONCLUSION(S): Intrauterine injection of 500 IU of hCG before ET statistically significantly improved the implantation and pregnancy rates in IVF/ICSI. CLINICAL TRIALS.GOV NUMBER: NCT 01030393. PMID- 22047665 TI - Seminal leukocytes are Good Samaritans for spermatozoa. AB - OBJECTIVE: To assess the effect of leukocytospermia on assisted reproductive technology outcomes. DESIGN: Retrospective analysis. SETTING: University laboratory. PATIENT(S): Couples attending the infertiliy clinic and involved in ART program for IVF or ICSI. INTERVENTION(S): During a 7-year follow-up in an assisted reproductive technology program, leukocytospermia was routinely determined using the peroxidase technique. Donor sperm were excluded from the study. MAIN OUTCOME MEASURE(S): Egg retrievals (N = 3,508) were distributed in 3 groups according to the leukocyte levels in semen from which fertilizing sperm were extracted: group 1, absence of leukocytes (n = 3,026); group 2, moderate leukocytospermia (<10(6)/mL) (n = 344); or group 3, high leukocytospermia (>=10(6)/mL) (n = 138). They resulted in 1,463 IVF and 2,045 intracytoplasmic sperm injection procedures that gave 802 clinical pregnancies. RESULT(S): Surprisingly, the fertilization rate, cleavage rate, clinical pregnancy rate, gestational age, and mean infant weight were significantly improved when seminal leukocytes were present, regardless of the technique used. The only negative side effects associated with a high level of seminal leukocytes (group 3) were an elevated rate of early pregnancy loss (from 26.6% to 40.5%) and a 3-fold increase in the percentage of ectopic pregnancies. CONCLUSION(S): At moderate levels (<10(6)/mL), leukocytospermia appears to be physiologic. It is associated with improved sperm fertilization ability and pregnancy outcome. At higher concentrations, leukocytospermia alters neither sperm fertilization ability nor the probability of clinical pregnancy when compared with nonleukocytic patients with infertility. However, the pregnancy outcome is reduced. PMID- 22047666 TI - Mutations in PMCA2 and hereditary deafness: a molecular analysis of the pump defect. AB - The inner ear converts sound waves into hearing signals through the mechanoelectrical transduction (MET) process. Deflection of the stereocilia bundle of hair cells causes the opening of channels that allow the entry of endolymph K(+) and Ca(2+). Ca(2+) that enters is crucial to the hearing process and is exported to the endolymph by the plasma membrane Ca(2+) pump (isoform PMCA2w/a): disturbances of the balance between Ca(2+) penetration and ejection, e.g. by pump mutations, generate deafness. Hearing loss caused by PMCA defects is frequently exacerbated by mutations in cadherin 23, a single pass stereociliar Ca(2+) binding protein that forms the tip links which permit the deflection of the stereocilia bundle and thus the opening of the MET channels. The PMCA2w/a pump ejects Ca(2+) to the endolymph even in the absence of the natural activator calmodulin. This satisfies the special Ca(2+) homeostasis requirements of the stereocilia/endolymph system. Here we have analyzed a mice and a human previously described pump mutant. The human mutant only exacerbated the deafness produced by a cadherin 23 mutation. The murine mutant overexpressed in model cells displayed an evident defect both in the basal activity of the pump and in the long range ejection of Ca(2+), the human mutant instead failed to impair the Ca(2+) ejection by the pump. PMID- 22047667 TI - [Drug prescriptions and demographic indicators in a diabetic population in Argentina]. AB - OBJECTIVE: To analyse prescription patterns for antihyperglycemic drugs and co medication in a group of diabetic patients regarding demographic variables. METHOD: Observational, cross-sectional study performed from the prescriptions of diabetic patients who attended a public health service in Argentina during 2008 2009. The programme Epidat 3.1 was used for statistical analysis. RESULTS: We included 813 patients, among which 455 (56%) were women. There was a greater prevalence of women under 40 years old (OR: 1.64; 95% CI: 1.05-2.56). Sixty-six point seven percent (n=542) of the population used at least one drug acting on the cardiovascular system, finding a positive statistical association between frequency of use and age (P<.00001). CONCLUSIONS: We found that there was a higher prevalence of women than men with early onset of type 2 diabetes mellitus. There were no differences between the sexes regarding frequency of use of drugs for the cardiovascular system. PMID- 22047668 TI - Elevated plasma corticosterone increases metabolic rate in a terrestrial salamander. AB - Plasma glucocorticoid hormones (GCs) increase intermediary metabolism, which may be reflected in whole-animal metabolic rate. Studies in fish, birds, and reptiles have shown that GCs may alter whole-animal energy expenditure, but results are conflicting and often involve GC levels that are not physiologically relevant. A previous study in red-legged salamanders found that male courtship pheromone increased plasma corticosterone (CORT; the primary GC in amphibians) concentrations in males, which could elevate metabolic processes to sustain courtship behaviors. To understand the possible metabolic effect of elevated plasma CORT, we measured the effects of male courtship pheromone and exogenous application of CORT on oxygen consumption in male red-legged salamanders (Plethodon shermani). Exogenous application of CORT elevated plasma CORT to physiologically relevant levels. Compared to treatment with male courtship pheromone and vehicle, treatment with CORT increased oxygen consumption rates for several hours after treatment, resulting in 12% more oxygen consumed (equivalent to 0.33 J) during our first 2h sampling period. Contrary to our previous work, treatment with pheromone did not increase plasma CORT, perhaps because subjects used in this study were not in breeding condition. Pheromone application did not affect respiration rates. Our study is one of the few to evaluate the influence of physiologically relevant elevations in CORT on whole-animal metabolism in vertebrates, and the first to show that elevated plasma CORT increases metabolism in an amphibian. PMID- 22047669 TI - Assessing therapeutic competence in cognitive therapy for social phobia: psychometric properties of the cognitive therapy competence scale for social phobia (CTCS-SP). AB - BACKGROUND: There has been considerable acknowledgement in treatment outcome research that, although the assessment of treatment integrity is essential in many respects, it requires great effort as well as resources and is therefore often neglected. AIMS: In order to fill this gap, the Cognitive Therapy Competence Scale for Social Phobia (CTCS-SP) was developed, based on the Cognitive Therapy Scale, to measure therapist competence in delivering cognitive therapy for social phobia. The aim of the present study was to investigate interrater reliability, internal consistency and retest reliability of the scale. METHOD: Raters evaluated therapist competence from 161 videotaped sessions (98 patients) selected from 234 cognitive treatments within a multi-centre study. RESULTS: Interrater-reliability was found to be high for the overall score (ICC = .81) and moderate for individual items (ICC = .62-.92). Internal consistency and retest reliability were also found to be high (Cronbach's alpha = .89; (ICCretest = .86). CONCLUSIONS: The results indicate that the CTCS-SP is highly reliable. As even individual items yield satisfactory reliability, the scale can be used in various fields of research, including the measurement of changes in skill acquisition and the impact of competence on outcome criteria. PMID- 22047670 TI - Effects of a radiation dose reduction strategy for computed tomography in severely injured trauma patients in the emergency department: an observational study. AB - BACKGROUND: Severely injured trauma patients are exposed to clinically significant radiation doses from computed tomography (CT) imaging in the emergency department. Moreover, this radiation exposure is associated with an increased risk of cancer. The purpose of this study was to determine some effects of a radiation dose reduction strategy for CT in severely injured trauma patients in the emergency department. METHODS: We implemented the radiation dose reduction strategy in May 2009. A prospective observational study design was used to collect data from patients who met the inclusion criteria during this one year study (intervention group) from May 2009 to April 2010. The prospective data were compared with data collected retrospectively for one year prior to the implementation of the radiation dose reduction strategy (control group). By comparison of the cumulative effective dose and the number of CT examinations in the two groups, we evaluated effects of a radiation dose reduction strategy. All the patients met the institutional adult trauma team activation criteria. The radiation doses calculated by the CT scanner were converted to effective doses by multiplication by a conversion coefficient. RESULTS: A total of 118 patients were included in this study. Among them, 33 were admitted before May 2009 (control group), and 85 were admitted after May 2009 (intervention group). There were no significant differences between the two groups regarding baseline characteristics, such as injury severity and mortality. Additionally, there was no difference between the two groups in the mean number of total CT examinations per patient (4.8 vs. 4.5, respectively; p = 0.227). However, the mean effective dose of the total CT examinations per patient significantly decreased from 78.71 mSv to 29.50 mSv (p < 0.001). CONCLUSIONS: The radiation dose reduction strategy for CT in severely injured trauma patients effectively decreased the cumulative effective dose of the total CT examinations in the emergency department. But not effectively decreased the number of CT examinations. PMID- 22047671 TI - Neural regulation of the immune system modulates hypertension-induced target organ damage. AB - Innate and acquired immune mechanisms are involved in hypertension-induced target organ damage. Immunosuppressive treatments directed at T lymphocytes, NF-kappaB activation, or tumor necrosis factor-alpha production are all successful in ameliorating cardiac or renal injury. Recently, important modulatory functions involving the autonomic nervous system have been uncovered. Involved are an afferent detection arm that sends vagal-mediated signals to the brain and an efferent arm that includes the spleen and important nicotinic acetylcholine receptor subunit. The signaling attenuates inflammatory activity. Splenectomy or operations that injure the vagus or splenic abrogate these important protective mechanisms. Vagal stimulation, either electrical or pharmacological, could provide additional protection. The field of neuroimmunology will become increasingly important to cardiovascular clinicians. PMID- 22047672 TI - Stand-off spatial offset Raman spectroscopy for the detection of concealed content in distant objects. AB - A pulsed (4.4 ns pulse length) frequency-doubled Nd:YAG laser operated at 10 Hz was used to generate Raman scattering of samples at a distance of 12 m. The scattered light was collected by a 6 in. telescope, and the Raman spectrum was recorded using an Acton SP-2750 spectrograph coupled to a gated intensified charge-coupled device (ICCD) detector. Applying a spatial offset between the point where the laser hit the sample and the focus of the telescope on the sample enabled collection of Raman photons that were predominantly generated inside the sample and not from its surface. This is especially effective when the content of concealed objects should be analyzed. High-quality Raman spectra could be recorded, within 10 s of data acquisition, from a solid (NaClO(3)) as well as a liquid (isopropyl alcohol) placed inside a 1.5 mm thick opaque low-density polyethylene (LDPE) plastic bottle. The applied spatial offset was also advantageous in cases where the surface of the container was highly fluorescent. In such a situation, Raman spectra of the sample could not be recorded when the sampling volume (telescope observation field) coincided with the focus of the excitation laser. However, with the use of a spatial offset of some millimeters, a clear Raman spectrum of the content (isopropyl alcohol) in a strongly fluorescent plastic container was obtained. PMID- 22047673 TI - A geometric morphometric analysis of hominin upper premolars. Shape variation and morphological integration. AB - This paper continues the series of articles initiated in 2006 that analyse hominin dental crown morphology by means of geometric morphometric techniques. The detailed study of both upper premolar occlusal morphologies in a comprehensive sample of hominin fossils, including those coming from the Gran Dolina-TD6 and Sima de los Huesos sites from Atapuerca, Spain, complement previous works on lower first and second premolars and upper first molars. A morphological gradient consisting of the change from asymmetric to symmetric upper premolars and a marked reduction of the lingual cusp in recent Homo species has been observed in both premolars. Although percentages of correct classification based on upper premolar morphologies are not very high, significant morphological differences between Neanderthals (and European middle Pleistocene fossils) and modern humans have been identified, especially in upper second premolars. The study of morphological integration between premolar morphologies reveals significant correlations that are weaker between upper premolars than between lower ones and significant correlations between antagonists. These results have important implications for understanding the genetic and functional factors underlying dental phenotypic variation and covariation. PMID- 22047680 TI - Mental incapacity in hospitalised patients undergoing percutaneous endoscopic gastrostomy insertion. AB - BACKGROUND & AIMS: Decisions to insert percutaneous endoscopic gastrostomy (PEG) tubes may be difficult because patients have serious underlying disease, and the procedure has associated risks. Patients may also lack mental capacity to consent to PEG insertion. This study aimed to prospectively determine the prevalence of mental incapacity in hospitalised patients undergoing PEG insertion. METHODS: Mental capacity was assessed using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) in 72 consecutive inpatients referred for PEG insertion. Cognitive function was measured using the Mini-Mental State Examination (MMSE). Sixty eight inpatients and 69 outpatients having diagnostic upper gastrointestinal (UGI) endoscopy were similarly studied. RESULTS: Thirty nine of the PEG patients had suffered stroke, and none had a primary diagnosis of dementia. Seventy four % (53/72) of inpatients referred for PEG, 22% (15/68) of inpatients having UGI endoscopy, and 3% (2/69) of outpatients having UGI endoscopy, lacked mental capacity, p < 0.001. MMSE scores were normal in just 18% of inpatients having PEG, in 72% of inpatients having UGI endoscopy, and in 91% of outpatients having UGI endoscopy, p < 0.001. CONCLUSION: Amongst inpatients undergoing PEG insertion there is a high prevalence (three-quarters patients) of mental incapacity to consent to this important intervention. Decisions have to be made on behalf of most inpatients referred for PEG insertion. PMID- 22047681 TI - Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib +/- megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. AB - BACKGROUND & AIMS: A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib +/- megestrol acetate for the treatment of cancer related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and 6-min walk test. METHODS: Sixty eligible patients were randomly assigned to: arm 1, L carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. RESULTS: The results did not show a significant difference between tre atment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. CONCLUSIONS: The results of the present study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment. PMID- 22047682 TI - A revertible, autonomous, self-assembled DNA-origami nanoactuator. AB - A DNA-origami actuator capable of autonomous internal motion in accord to an external chemical signal was designed, built, operated and imaged. The functional DNA nanostructure consists of a disk connected to an external ring in two, diametrically opposite points. A single stranded DNA, named probe, was connected to two edges of the disk perpendicularly to the axis of constrain. In the presence of a hybridizing target molecule, the probe coiled into a double helix that stretched the inner disk forcing the edges to move toward each other. The addition of a third single stranded molecule that displaced the target from the probe restored the initial state of the origami. Operation, dimension and shape were carefully characterized by combining microscopy and fluorescence techniques. PMID- 22047683 TI - Long-term (<= 50 years) results of patients after mitral valve commissurotomy--a single-center experience. AB - OBJECTIVE: Currently, in Middle Europe, closed and open mitral valve commissurotomy (MVC) is rarely done and has been replaced by catheter-based balloon procedures. Especially under these circumstances, data on the long-term outcomes after surgical interventions are important. METHODS: From 1955 to 1989, 268 patients (75 male and 193 female patients) with mostly rheumatic or infectious mitral stenoses underwent closed (n = 151) or open (n = 117) surgical procedures. The mean age at surgery was 41.2 +/- 11.1 years; 19 patients (7.1%) died within the first 30 days after surgery. RESULTS: The 50-year follow-up was complete for 215 patients (80.2%). The survival rate at 10, 20, and 30 years after surgery was 80.2%, 58.6%, and 41.8%, respectively. The differences after closed and open MVC were nonsignificant. At the latest follow-up, 32 patients were alive and had a mean New York Heart Association functional classification of 2.7. The 10-, 20-, and 30-year freedom from reoperation rate was 93.2%, 82.9%, and 76.0% for the closed intervention group and 88.5%, 80.3%, and 78.7% for the open intervention groups. Again, the differences were nonsignificant. The main cause for reoperation was recurrent fibrosis of the mitral valve. Most patients (n = 51) received mechanical valves, 5 a bioprothesis, and 8 repeat MVC. Four patients required a third intervention. CONCLUSIONS: In Middle Europe, closed and open MVCs are now rarely performed, but the ultra-long-term results are excellent and serve as a standard for the now-established balloon valvuloplasty. MVCs remain an option for pregnant women. In third world clinical conditions, closed MVC remains a less expensive alternative. PMID- 22047684 TI - Effects of glutaraldehyde concentration, pretreatment time, and type of tissue (porcine versus bovine) on postimplantation calcification. AB - OBJECTIVE: Our objective was to evaluate the effects of glutaraldehyde (GA) concentration, time of pretreatment, and type of tissue (porcine vs bovine) on quantitative and qualitative postimplant calcification of tissues. METHODS: Freshly obtained porcine and bovine pericardial tissues were each treated with increasing concentrations of GA (controls, 0.3125%, 0.625%, and 1.2%) for a fixed time (15 minutes) or increasing exposure times (5, 10, 20, and 30 minutes) at a fixed concentration of GA (0.625%). Pretreated tissues were subcutaneously implanted in 10-week-old Sprague-Dawley rats for 45 days before explantation. Quantitative calcium analysis was performed by flame atomic spectrophotometry. Histologic examination of tissue samples with hematoxylin and eosin and von Kossa staining was performed for cellular and inflammatory response, autolysis, and calcification. RESULTS: Two-way analysis of variance indicated significantly greater calcium levels at 1.2% compared with each lower concentration for both porcine and bovine samples (P < .01). Significantly lower calcium levels were detected with increased exposure time in porcine samples (F = 6.97; P < .001); however, no significant differences in calcium levels were observed between different exposure times for bovine samples (F = 1.46; P = .23). Histologic evidence of inflammatory response with infiltration with mononuclear cells, fibroblasts, and histiocytes was seen in all grafts; however, it varied from mild to severe without any pattern. There were no differences in degree or pattern of inflammatory response according to GA concentration or time of exposure. Estimation of amount of calcification by histologic examination correlated with the quantitative assay. CONCLUSIONS: Increasing GA concentration leads to greater calcification with a sharp rise in calcium levels above a concentration of 0.625%, in both bovine and porcine pericardial tissues. At a concentration of 0.625%, increasing pretreatment time is inversely related to tissue calcification for porcine pericardium but not for bovine pericardium. Differences in the tissue composition in terms of cellular content and composition of the extracellular matrix could account for the observed findings. PMID- 22047685 TI - Bioengineered self-seeding heart valves. AB - OBJECTIVE: Mechanical and biological prostheses are used to replace damaged heart valves but are associated with significant morbidities. Although there is increased interest in bioengineering cell-seeded heart valve scaffolds, it is a time-consuming and technically difficult process. The goal of this project was to engineer self-seeding heart valves that mature quickly in vivo and have a shorter preparation time. METHODS: Porcine pulmonary valves were decellularized using detergent methods and then either (1) left untreated (unconjugated, n = 6), (2) reseeded with autologous endothelial progenitor cell-derived endothelial cells (cell-seeded, n = 4), or (3) conjugated with CD133 antibodies (conjugated, n = 8). The valve constructs were transplanted into the pulmonary position of sheep using standard surgical techniques. After 1 or 3 months, the implants were removed and assessed for cell and matrix content as well as biomechanical properties. RESULTS: Endothelial cells expressing von Willebrand factor lined the entire length of both ventricular and arterial surfaces of conjugated valves by 1 month after implantation. Interstitial cell and structural protein content of conjugated valves increased from 1 month to 3 months with interstitial expression of metalloproteinase-9 and new collagen formation. In contrast, there were few endothelial or interstitial cells associated with unconjugated, or cell-seeded valves at any time point. No calcification or thrombi were noted on any of the valves. Young's modulus and tensile strength was greater in the conjugated valves versus unconjugated or cell-seeded valves. CONCLUSIONS: Results indicate that tissue-engineered heart valve replacement constructs can be made quickly and therefore may be a clinically relevant option for patients needing heart valve surgery in a timely fashion. PMID- 22047686 TI - Quality of life of patients after retropubic prostatectomy - pre- and postoperative scores of the EORTC QLQ-C30 and QLQ-PR25. AB - BACKGROUND: Patients with newly diagnosed early stage prostate cancer (PCa) face a difficult choice of different treatment options with curative intention. They must consider both goals of optimising quantity and quality of life. The quality of life (QoL) is a psychometric outcome which is measured using validated questionnaires. Only few data are published concerning pre - and postoperative QoL. METHODS: This study investigated pre perative QoL of 185 patients who consecutively underwent open radical retropubic prostatectomy for organ-confined PCa to postoperative QoL of another 185 patients. The EORTC QLQ-C30, EORTC QLQPR25 module and 24 h ICS pad test were used (mean follow-up 28.6 months). RESULTS: The examined symptom scores of the EORTC QLQ-PR25 were on lowest level. In the dyspnoea symptom score differences of age emerged: the amount of patients who are short of breath rose significantly in older patients after surgery (p < 0.05 paired, two-tailed student's t-test).. Lastly, the urinary symptom score was found postal-therapeutically low; this fact was age independent. The results of sexual symptom score need to be taken into consideration, since prostatectomy resulted in a significant reduction of sexual activity independent of age. All functioning scales postoperatively reached high values without significant changes (p > 0.05 student's t-test ), which implies a high QoL after surgery. A reliable and satisfying status of continence was found in our patients after retropubic prostatectomy. A high rate of patients (89.2%) would choose retropubic prostatectomy again. CONCLUSION: Retropubic prostatectomy represents a reliable and accepted procedure in the treatment of organ-confined PCa. For the first time it could be shown that patients' QoL remained on a high level after retropubic prostatectomy. Nevertheless, the primary avoidance or postoperative therapy of erectile dysfunction should be in the focus of surgeons. PMID- 22047687 TI - Synthesis and evaluation of a bifunctional chelate for development of Bi(III) labeled radioimmunoconjugates. AB - A new bifunctional ligand C-DEPA was designed and synthesized as a component for antibody-targeted radiation therapy (radioimmunotherapy, RIT) of cancer. C-DEPA was conjugated to a tumor targeting antibody, trastuzumab, and the corresponding C-DEPA-trastuzumab conjugate was evaluated for radiolabeling kinetics with (205/6)Bi. C-DEPA-trastuzumab conjugate rapidly bound (205/6)Bi, and (205/6)Bi-C DEPA-trastuzumab conjugate was stable in human serum for 72 h. The in vitro radiolabeling kinetics and serum stability data suggest that C-DEPA is a potential chelate for preclinical RIT applications using (212)Bi and (213)Bi. PMID- 22047688 TI - CCR2 receptor antagonists: optimization of biaryl sulfonamides to increase activity in whole blood. AB - A series of biarylsulfonamides was identified as hCCR2 receptor antagonist but suffered from high plasma protein binding resulting in a >100 fold shift in activity in a functional GTPgammaS assay run in tandem in the presence and absence of human serum albumin. Introduction of an aryl amide with ethylenediamine linker led to compounds with reduced shifts and improved activity in whole blood. PMID- 22047689 TI - Novel amino-piperidines as potent antibacterials targeting bacterial type IIA topoisomerases. AB - We have identified a series of amino-piperidine antibacterials with a good broad spectrum potency. We report the investigation of various subunits in this series and advanced studies on compound 8. Compound 8 possesses good pharmacokinetics, broad spectrum antibacterial activity and demonstrates oral efficacy in a rat lung infection model. PMID- 22047690 TI - Conjugation of spermine enhances cellular uptake of the stapled peptide-based inhibitors of p53-Mdm2 interaction. AB - We report the first synthesis of the C-terminally spermine-conjugated stapled peptide-based inhibitors of the p53-Mdm2 interaction. Subsequent biological, biophysical and cellular uptake assays with the spermine-conjugated stapled peptides revealed that spermine conjugation minimally affects biological activity while significantly increases peptide helicity and cellular uptake without apparent cytotoxicity. PMID- 22047691 TI - The discovery of AZD9164, a novel muscarinic M3 antagonist. AB - The optimization of a new series of muscarinic M(3) antagonists is described, leading to the identification of AZD9164 which was progressed into the clinic for evaluation of its potential as a treatment for COPD. PMID- 22047692 TI - Nicotinic acids: liver-targeted SCD inhibitors with preclinical anti-diabetic efficacy. AB - An in vitro screening protocol was used to transform a systemically-distributed SCD inhibitor into a liver-targeted compound. Incorporation of a key nicotinic acid moiety enables molecular recognition by OATP transporters, as demonstrated by uptake studies in transfected cell lines, and likely serves as a critical component of the observed liver-targeted tissue distribution profile. Preclinical anti-diabetic oGTT efficacy is demonstrated with nicotinic acid-based, liver targeting SCD inhibitor 10, and studies with a close-structural analog devoid of SCD1 activity, suggest this efficacy is a result of on-target activity. PMID- 22047693 TI - Antifungal activity of 2alpha,3beta-functionalized steroids stereoselectively increases with the addition of oligosaccharides. AB - Invasive fungal infections pose a significant problem to the immune-compromised. Moreover, increased resistance to common antifungals requires development of novel compounds that can be used to treat invasive fungal infections. Naturally occurring steroidal glycosides have been shown to possess a range of functional antimicrobial properties, but synthetic methodology for their development hinders thorough exploration of this class of molecules and the structural components required for broad spectrum antifungal activity. In this report, we outline a novel approach to the synthesis of glycoside-linked functionalized 2alpha,3beta cholestane and spirostane molecules and present data from in vitro screenings of the antifungal activities against human fungal pathogens and as well as mammalian cell toxicity of these derivatives. PMID- 22047694 TI - Antiprotozoal activity of proton-pump inhibitors. AB - Parasitic diseases are still a major health problem in developing countries. In our effort to find new antiparasitic agents, in this Letter we report the in vitro antiprotozoal activity of omeprazole, lansoprazole, rabeprazole and pantoprazole against Trichomonas vaginalis, Giardia intestinalis and Entamoeba histolytica. Molecular modeling studies were an important tool to highlight the potential antiprotozoal activity of these drugs. Experimental evaluations revealed a strong activity for all compounds tested. Rabeprazole and pantoprazole were the most active compounds, having IC(50) values in the nanomolar range, which were even better than metronidazole, the drug of choice for these parasites. PMID- 22047695 TI - Exploration of in vitro time point quantitative evaluation of newly synthesized benzimidazole and benzothiazole derivatives as potential antibacterial agents. AB - Present communication deals with the in vitro time point quantitative antibacterial evaluation of newly synthesized 1,2-disubstituted benzimidazoles (3a-p) and 2-substituted benzothiazoles (5a-h) against Gram-positive bacteria Staphylococcus aureus, Bacillus cereus, and Gram-negative bacteria Vibrio cholerae, Shigella dysenteriae and Escherichia coli. These compounds were synthesized under mild reaction conditions using Al(2)O(3)-Fe(2)O(3) nanocrystals as heterogeneous catalyst. Bio-evaluation studies revealed that, compounds 3a, 5a and 5d exhibited moderate to good antibacterial activity against all the tested bacterial stains. The compounds 3a, 3f and 5a have shown enhanced inhibitory activity compared with standard antibacterial drug ciprofloxacin against V. cholerae, B. cereus, and S. dysenteriae, respectively. Additionally, the compounds 3a, 3e, 3f, 3h and 5b displayed complete bactericidal activity within 24 h, whereas ciprofloxacin took 48 h to kill those bacteria completely. PMID- 22047696 TI - Structure-activity relationships of ganoderma acids from Ganoderma lucidum as aldose reductase inhibitors. AB - A series of lanostane-type triterpenoids, known as ganoderma acids were isolated from the fruiting body of Ganoderma lucidum. Some of these compounds were identified as active inhibitors of the in vitro human recombinant aldose reductase. To clarify the structural requirement for inhibition, some structure activity relationships were determined. Our structure-activity studies of ganoderma acids revealed that the OH substituent at C-11 is an important feature and the carboxylic group in the side chain is essential for the recognition of aldose reductase inhibitory activity. Moreover, double bond moiety at C-20 and C 22 in the side chain contributes to improving aldose reductase inhibitory activity. In the case of ganoderic acid C2, all of OH substituent at C-3, C-7 and C-15 is important for potent aldose reductase inhibition. These results provide an approach to understanding the structural requirements of ganoderma acids from G. lucidum for aldose reductase inhibitor. This understanding is necessary to design a new-type of aldose reductase inhibitor. PMID- 22047697 TI - Fluorescent reporters of monoamine transporter distribution and function. AB - Serotonin is a monoamine serving as a chemical messenger in diverse brain regions, as well as in blood and various other organs. We synthesized six ethylamine functionalized fluorophores as fluorescent probes for serotonin. The one with best spectral properties and aqueous solubility, 6-amino-2-(2 aminoethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione, was studied in detail both in vivo and in vitro. It was shown to act as a ligand for serotonin transporter (SERT) without acute cerebral or cardiovascular toxicity or adverse effects. Fluorescent serotonin analogs can be used for direct visualization of SERT distribution and activity in live tissue. PMID- 22047698 TI - Novel cytotoxic chalcones from Litsea rubescens and Litsea pedunculata. AB - Two novel flavonoids with chalcone skeleton, together with seven known flavonoids, were isolated from the stem barks of Litsea rubescens and Litsea pedunculata. The structures of the new compounds were elucidated on the basis of spectral methods including IR, UV, 1D and 2D NMR. The new chalcones were found to contain the rare epoxy or ethylidenedioxy group. This is the first report on the presence of chalcone in the plant genus Litsea. The cytotoxic potential of two new chalcones was evaluated in vitro against three human tumor cell lines. Both new chalcones displayed potent cytotoxic activities against myeloid leukaemia (HL 60) and epidermoid carcinoma (A431) cell lines and more active than cisplatin (DDP). Interestingly, compound 1 exhibited cytotoxic activity against HL-60 with IC(50) value 2.1-fold more sensitive to DDP. PMID- 22047699 TI - Use of self-expandable stents in the treatment of bariatric surgery leaks: a systematic review and meta-analysis. AB - BACKGROUND: Bariatric surgery leaks can result in significant morbidity and mortality. Endoscopic placement of self-expandable stents (SESs) is emerging as a less-invasive alternative to surgery for the treatment of leaks. OBJECTIVE: To evaluate the success of SESs in the treatment of bariatric surgery leaks. DESIGN: Studies using SESs in the management of bariatric surgery leaks were selected. Success of SES treatment was defined as radiographic evidence of leak closure after stent removal. Articles were searched in MEDLINE, PubMed, Ovid, and Cochrane Register of Controlled Trials. Pooled proportions were calculated by using fixed- and random-effects models. Publication bias was calculated by using the Begg-Mazumdar and Harbord bias estimators. RESULTS: A total of 189 relevant articles were reviewed of which 7 studies (67 patients with leaks) met inclusion criteria. The pooled proportion of successful leak closures by using SESs was 87.77% (95% CI, 79.39%-94.19%). The pooled proportion of successful endoscopic stent removal was 91.57% (95% CI, 84.22%-96.77%). Stent migration was noted in 16.94% (95% CI, 9.32%-26.27%). Test of heterogeneity gave a P value >.10. There was no publication bias. LIMITATIONS: Small retrospective studies, different types of stents used. CONCLUSION: Endoscopic placement of SESs is a minimally invasive, safe, and effective alternative in the management of leaks after bariatric surgery. The use of SESs can minimize the need for surgical revision and improve patient outcomes. PMID- 22047700 TI - Single-operator cholangioscopy for the extraction of cystic duct stones (with video). PMID- 22047701 TI - The effect of hand dominance on martial arts strikes. AB - The main goal of this study was to compare dominant and non-dominant martial arts palm strikes under different circumstances that usually happen during martial arts and combative sports applications. Seven highly experienced (10+/-5 years) right hand dominant Kung Fu practitioners performed strikes with both hands, stances with left or right lead legs, and with the possibility or not of stepping towards the target (moving stance). Peak force was greater for the dominant hand strikes (1593.76+/-703.45 N vs. 1042.28+/-374.16 N; p<.001), whereas no difference was found in accuracy between the hands (p=.141). Additionally, peak force was greater for the strikes with moving stance (1448.75+/-686.01 N vs. 1201.80+/-547.98 N; p=.002) and left lead leg stance (1378.06+/-705.48 N vs. 1269.96+/-547.08 N). Furthermore, the difference in peak force between strikes with moving and stationary stances was statistically significant only for the strikes performed with a left lead leg stance (p=.007). Hand speed was higher for the dominant hand strikes (5.82+/-1.08 m/s vs. 5.24+/-0.78 m/s; p=.001) and for the strikes with moving stance (5.79+/-1.01 m/s vs. 5.29+/-0.90 m/s; p<.001). The difference in hand speed between right and left hand strikes was only significant for strikes with moving stance. In summary, our results suggest that the stronger palm strike for a right-handed practitioner is a right hand strike on a left lead leg stance moving towards the target. PMID- 22047702 TI - Carbapenem stewardship: does ertapenem affect Pseudomonas susceptibility to other carbapenems? A review of the evidence. AB - The group 2 carbapenems (imipenem, meropenem and, more recently, doripenem) have been a mainstay of treatment for patients with serious hospital infections caused by Pseudomonas aeruginosa, Enterobacteriaceae and other difficult-to-treat Gram negative pathogens as well as mixed aerobic/anaerobic infections. When ertapenem, a group 1 carbapenem, was introduced, questions were raised about the potential for ertapenem to select for imipenem- and meropenem-resistant Pseudomonas. Results from ten clinical studies evaluating the effect of ertapenem use on the susceptibility of Pseudomonas to carbapenems have uniformly shown that ertapenem use does not result in decreased Pseudomonas susceptibility to these antipseudomonal carbapenems. Here we review these studies evaluating the evidence of how ertapenem use affects P. aeruginosa as well as provide considerations for ertapenem use in the context of institutional stewardship initiatives. PMID- 22047703 TI - Retrospective case-control analysis of patients with staphylococcal infections receiving daptomycin or glycopeptide therapy. AB - Glycopeptides have been considered the antimicrobials of choice for serious meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-resistant coagulase-negative staphylococci (MR-CoNS) infections for several years. Daptomycin is a new option for the treatment of these infections, including those exhibiting reduced susceptibility to glycopeptides. The aim of this study was to compare glycopeptides and daptomycin for the treatment of infections caused by MRSA or MR-CoNS. Data for 106 patients with bloodstream infections (bacteraemia or infective endocarditis) or skin and soft-tissue infections (SSTIs) were retrospectively reviewed, of which 43 were treated with daptomycin (DAP group) and 63 were treated with vancomycin or teicoplanin (GLYCO group). Patients included in the two comparison groups were homogeneous in terms of age, risk factors and clinical severity. Aetiology was mainly represented by MRSA in both groups, followed by various species of MR-CoNS. Daptomycin was used more frequently in patients with central venous catheter-associated bacteraemia or pacemaker-associated infection. Patients with SSTIs included in the GLYCO group had a longer mean duration of antibiotic therapy (18.2 days vs. 14.6 days; P=0.009) and a longer mean length of hospital stay (28.2 days vs. 19.6 days; P=0.01) compared with those included in the DAP group. A longer mean duration of antibiotic therapy was also observed in patients with bloodstream infections receiving glycopeptide therapy (25.6 days vs. 18 days; P=0.004). In conclusion, the good clinical efficacy of daptomycin is associated with a more rapid resolution of the clinical syndrome and a reduced length of hospitalisation. This latter aspect may have important pharmacoeconomic implications, promoting the use of daptomycin in the clinical setting. PMID- 22047704 TI - Co-infection with Opisthorchis viverrini and Haplorchis taichui detected by human fecal examination in Chomtong district, Chiang Mai Province, Thailand. AB - Diseases caused by the liver fluke, Opisthorchis viverrini and the minute intestinal fluke, Haplorchis taichui, are clinically important, especially in the Northeast and North regions of Thailand. It is often difficult to distinguish between these trematode species using morphological methods due to the similarity of their eggs and larval stages both in mixed and co-infections. A sensitive, accurate, and specific detection method of these flukes is required for an effective epidemiological control program. This study aimed to determine the prevalence of O. viverrini and H. taichui infections in human feces by using formalin-ether sedimentation and high annealing temperature random amplified polymorphic DNA (HAT-RAPD) PCR methods. Fecal specimens of people living along the Mae Ping River, Chomtong district were examined seasonally for trematode eggs using a compound microscope. Positive cases were analyzed in HAT-RAPD, DNA profiles were compared with adult stages to determine the actual species infected, and specific DNA markers of each fluke were also screened. Our results showed that out of 316 specimens, 62 were positive for fluke eggs which were pre identified as O. viverrini and H. taichui. In addition, co-infection among these two fluke species was observed from only two specimens. The prevalence of H. taichui infections peaked in the hot-dry (19.62%), gradually decreased in the rainy (18.18%), and cool-dry seasons (14.54%), respectively. O. viverrini was found only in the hot-dry season (6.54%). For molecular studies, 5 arbitrary primers (Operon Technologies, USA) were individually performed in HAT-RAPD-PCR for the generation of polymorphic DNA profiles. The DNA profiles in all 62 positives cases were the same as those of the adult stage which confirmed our identifications. This study demonstrates the mixed infection of O. viverrini and H. taichui and confirms the extended distribution of O. viverrini in Northern Thailand. PMID- 22047705 TI - Evaluation of perseveration in relation to panic-relevant responding: an initial test. AB - BACKGROUND: Perseveration reflects the tendency to engage in a behavior even when it is no longer rewarding nor produces the expected consequences. METHOD: The current study explored whether (1) individuals endorsing a recent (past 2 years) history of nonclinical panic attacks would report greater levels of perseveration compared to individuals without such a history; (2) whether individuals endorsing higher levels of perseveration would evidence greater panic-relevant responding to a 4-minute 10% carbon dioxide-enriched air challenge. RESULTS: Results indicated that individuals with, compared to without, a positive panic attack history endorsed significantly greater levels of perseveration. Additionally, greater pre-challenge levels of perseveration significantly predicted greater panic attack symptom severity as well as self-reported anxiety; these significant effects were evident above and beyond the variance accounted for by sex, trait level negative affectivity, panic attack status, and distress tolerance as well as shared variance with the related constructs of persistence and perfectionism. DISCUSSION: Together, the current findings provide initial, albeit preliminary, support for the utility of investigating perseveration in relation to models of panic psychopathology specifically, and offer a further empirical context for perseveration-psychopathology relations in general. PMID- 22047706 TI - The utility of fluorescence in situ hybridization analysis in diagnosing myelodysplastic syndromes is limited to cases with karyotype failure. AB - Fluorescence in situ hybridization (FISH) is being used increasingly in cytogenetic diagnosis of myelodysplastic syndromes (MDS). However, the utility of FISH in this role has not been well-defined. A total of 249 de novo MDS patients were submitted to karyotyping and FISH analysis for -5/del(5)(q31), 7/del(7)(q31), +8, -17/i(17)(q10), del(20)(q12), and -Y. Of the 234 patients with available karyotypic data, 143 cases (60.9%) demonstrated normal karyotype and 91 cases (39.1%) showed abnormal karyotype. FISH confirmed R-banding findings in 96.6% (226/234) of samples with successful karyotyping and detected cytogenetic abnormalities in 46.7% (7/15) of cases with karyotype failure. Of the 3.4% (8/234) patients showing discrepancies between FISH and R-banding, FISH revealed cytogenetic abnormalities in four patients with normal karyotypes and four patients with complex karyotypes. These results highlight FISH analysis has limited value in MDS cases with successful karyotyping and is only informative in MDS cases with karyotype failure. PMID- 22047707 TI - Tyrosine kinase inhibitor therapy for acute myeloid leukemia with late-appearing Philadelphia chromosome. PMID- 22047708 TI - Vitamin D insufficiency predicts time to first treatment (TFT) in early chronic lymphocytic leukemia (CLL). AB - Although vitamin D insufficiency is related to inferior prognosis in some cancers, limited data exist in hematologic malignancies. We evaluated the relationship between 25(OH)D serum levels and time to first treatment (TFT), a disease-specific end point, in 130 previously untreated Binet stage A chronic lymphocytic leukemia (CLL) patients. Measurement of 25(OH)D was performed by means of a direct, competitive chemiluminescence immunoassay using the DiaSorin LIAISON 25(OH)D TOTAL assay (DiaSorin, Inc., Stillwater, Minnesota). Overall, 41 patients (31.5%) had severe vitamin D insufficiency (<10 ng/mL), 66 (50.7%) had mild to moderate insufficiency (10-24 ng/mL), and 23 (17.6%) had 25(OH)D levels within the optimal range (25-80 ng/mL), with no relationship with between the season of sample collection and 25(OH)D level (P=0.188). A patient stratification according to these 3 groups led to significant difference in terms of TFT, with vitamin D insufficient patients having the shortest TFT (P=0.02). With respect to continuous 25(OH)D levels and clinical outcome, TFT was shorter as 25(OH)D decreased until a value of 13.5 ng/mL at which point the association of 25(OH)D and TFT remained constant. As a matter of fact, the 25(OH)D value of 13.5 ng/mL identified two patients subsets with different TFT risk (HR=1.91; 95% CI=1.06 3.44; P=0.03). In multivariate analysis the variable entering the model at a significant level were mutational status of IgVH (P<0.0001), serum thymidine kinase (P=0.02) and absolute lymphocyte count (P=0.03). Thus confirming the Mayo clinic experience, our data provide further evidence that 25(OH)D levels may be an important host factor influencing TFT of Binet stage A patients. Whether normalizing vitamin D levels may delay disease-progression of patients with early disease will require testing in future trials. PMID- 22047709 TI - DNA repair gene XPD and XRCC1 polymorphisms and the risk of febrile neutropenia and mucositis in children with leukemia and lymphoma. AB - The aim of the study is to investigate association between DNA repair gene XPD and XRCC1 polymorphisms and febrile neutropenia (FN) and mucositis. The study population consisted of 29 children with Burkitt lymphoma and 61 children with acute lymphoblastic leukemia. Analysis revealed that XRCC1194Trp allele showed a protective effect against longer FN and mucositis. There was also statistically increased risk for severe mucositis in patients with XRCC1Arg399Gln polymorphism. There are no studies that have examined this relationship before. Further studies with larger cohorts are needed to clarify the association. PMID- 22047710 TI - piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. AB - Piwi-interacting RNAs (piRNAs), new non-coding small RNAs, are association with chromatin organization, messenger RNA stability and genome structure. However, the roles of piRNA in carcinogenesis are not clearly defined. By using real-time reverse transcription-polymerase chain reaction technology, we found that the expression level of piR-823 in gastric cancer tissues was significant lower than that in non-cancerous tissues. After increase the level of piR-823 in gastric cancer cells, cell growth was inhibited. The results of xenograft nude mice model confirmed its tumor suppressive properties. All of the evidences indicated that piR-823 play a crucial role in the occult of gastric cancer. PMID- 22047711 TI - Protective and therapeutic effects of licorice in rats with acute tubular necrosis. AB - OBJECTIVES: Various protective and therapeutic effects such as antioxidant, anti inflammatory, anticancer, antihistaminic, and antibacterial effects have been depicted for licorice. However, its biological effects in the kidney are still not clear. Therefore, we aimed to investigate the efficiency of licorice in rats with gentamicin (GM)-induced acute tubular necrosis. DESIGN AND METHODS: Rats were randomized into the control group (only saline for 12 days), licorice group (licorice for 12 days), GM group (GM for 12 days), GM + licorice group, and licorice-treated GM group (licorice for 12 days after taking GM for 12 days). Blood urea, creatinine, and uric acid levels were measured and histopathological analyses of the kidneys were performed. The oxidative side of oxidant-antioxidant balance was evaluated by detecting lipid peroxidation (LPO) and total peroxide levels, and antioxidative side was determined by measuring total antioxidant capacity (TAC) and reduced glutathione (GSH) levels in plasma and kidney tissues. RESULTS: The oxidant-antioxidant balance seemed to be shifted to the oxidative side in the GM group when compared with the control and GM + licorice groups. In GM group, biochemical profiles showed a remarkable increase in blood uric acid, urea, and creatinine levels, and depletion of renal tissue and plasma TAC and GSH levels. In addition, histopathologic studies revealed severe acute tubular necrosis, congestion, and hyaline casts, verifying GM-induced nephrotoxicity. Licorice was effective in reduction of blood urea, creatinine, and uric acid levels, and also effective in decreasing the tubular necrosis score. Licorice treatment also significantly reduced LPO and total peroxide levels, and increased TAC and GSH levels in both renal tissue and blood. Moreover, these changes in rats subjected to the combined therapy (GM + licorice) were significantly less than those of GM group. CONCLUSIONS: Licorice ameliorates GM-induced nephrotoxicity and oxidative damage by scavenging oxygen free radicals, decreasing LPO, and improving antioxidant defense. PMID- 22047712 TI - [Sociodemographic factors and satisfaction related to the care received by women with breast cancer. Multicentre study]. AB - OBJECTIVES: Evaluate the level of satisfaction in the Medical Oncology Services in our Community of women with breast cancer, and analyse the influence of sociodemographic and clinical factors on their satisfaction. MATERIAL AND METHODS: Cross-sectional multicentre study using an anonymous and voluntary questionnaire completed by 225 women diagnosed with breast cancer. The tool used was the modified SERVQHOS, adapted to our context. We collected demographic and clinical data. To determine the reliability of the tool after the adjustments, a Cronbach's alpha analysis was performed. A descriptive analysis was also performed, as well as non-parametric statistics to study the influence of demographic variables on satisfaction. RESULTS: The best evaluated aspects were the kindness of the staff [4.30+/-0.83 (2-5)], the confidence transmitted by them [4.23+/-0.79 (2-5)] and personal treatment [4.12+/-0.88 (2-5)]. The worst evaluated was the ease of getting to the hospital [3.06+/-0.99 (1-5)], waiting time [3.16+/-1.00 (1-5)], state of consultations rooms [3.38+/-0.99 (1-5)] and punctuality of the sessions [3.38+/-1.05 (1-5)]. The overall satisfaction was 4.04+/-0.82 (1-5). Age influenced their assessment of the personal appearance of the staff (P=.04), the state of consultations rooms (P<00), the ease of getting to the hospital, and the quantity and quality of information received (P=01). Educational level influenced their satisfaction with personal appearance of the staff (P =03) and the state of consultations rooms (P=03). Women who worked and those who were temporary disabled women evaluated the appearance of personnel worst (P=02). The time from the diagnosis affected the satisfaction with the staff willingness to help (P<00) and therapy attendance, and the satisfaction with the ability to understand their needs (P=03). CONCLUSIONS: The individual characteristics of the participants influence their satisfaction. We have been able to identify deficient areas from their point of view, identifying important improvement opportunities in several aspects of care to work on in order to increase the quality of care. PMID- 22047713 TI - Demonstration of genes encoding virulence and virulence life-style factors in Brachyspira spp. isolates from pigs. AB - The distribution of many genes encoding virulence and virulence life-style (VL-S) factors in Brachyspira (B.) hyodysenteriae and other Brachyspira species are largely unknown. Their knowledge is essential e.g. for the improvement of diagnostic methods targeting the detection and differentiation of the species. Thus 121 German Brachyspira field isolates from diarrhoeic pigs were characterized down to the species level by restriction fragment length polymorphism analysis of the nox gene and subsequently subjected to polymerase chain reaction detecting VL-S genes for inner (clpX) and outer membrane proteins (OMPs: bhlp16, bhlp17.6, bhlp29.7, bhmp39f, bhmp39h), hemolysins (hlyA/ACP, tlyA), iron metabolism (ftnA, bitC), and aerotolerance (nox). For comparison, B. hyodysenteriae reference strains from the USA (n=7) and Australia (2) were used. Of all genes tested only nox was detected in all isolates. The simultaneous presence of both the tlyA and hlyA/ACP was restricted to the species B. hyodysenteriae. The hlyA infrequently occurred also in weakly hemolytic Brachyspira. Similarly to tlyA and hlyA all B. hyodysenteriae strains contained the ferritin gene ftnA which was also found in two Brachyspira intermedia isolates. OMP encoding genes were present in B. hyodysenteriae field isolates in rates of 0% (bhlp17.6, bhmp39h), 58.1% (bhlp29.7), and 97.3% (bhmp39f). Since the study revealed a high genetic heterogeneity among German B. hyodysenteriae field isolates differentiating them from USA as well as Australian strains, targets for diagnostic PCR were limited to the nox gene (genus specific PCR) as well as to the species specific nox(hyo) gene and the combination of hlyA and tlyA which allow to specifically detect B. hyodysenteriae. PMID- 22047714 TI - The surface-localised alpha-enolase of Mycoplasma suis is an adhesion protein. AB - Mycoplasma suis belongs to the haemotrophic mycoplasmas which colonise red blood cells of a wide range of vertebrates. Adhesion to red blood cells is the crucial step in the unique lifecycle of M. suis. Due to the lack of a cultivation system, identification of adhesion structures has been difficult. So far, only one adhesion protein, i.e. MSG1 was identified. In order to determine further adhesion molecules of M. suis, we screened genomic M. suis libraries and performed Southern blot hybridisation analyses of genomic M. suis DNA. The alpha enolase of M. suis was identified and analysed genetically and functionally. The encoding gene has 1623 bp in size. The deduced amino acid sequence showed an overall identity of 59.6-65.1% to alpha-enolases of other pathogenic mycoplasmas. The 540 aa M. suis alpha-enolase displays a size extension of about 90 aa in comparison to alpha-enolases of other mycoplasmas. Recombinant alpha-enolase expressed in Escherichia coli demonstrated immunogenicity in experimentally infected pigs. Immunoblot, confocal laser scanning microscopy and immune electron microscopy analysis using antibodies against recombinant alpha-enolase, indicate the membrane and surface localisation of native alpha-enolase in M. suis, though no typical signal sequences exist. Furthermore, we showed that recombinant alpha enolase binds to porcine erythrocyte lysate in a dose-dependent manner. E. coli transformants which express alpha-enolase on their surface acquire the ability to adhere to porcine red blood cells. In conclusion, our observations indicate that alpha-enolase could be involved in the adhesion of M. suis to porcine red blood cells. PMID- 22047715 TI - In vitro culture of blastocystis hominis in three liquid media and its usefulness in the diagnosis of blastocystosis. AB - BACKGROUND: Blastocystis hominis is a common protozoan in the human intestinal tract and can cause the so-called blastocystosis characterized by diarrhea. To date, its identification has depended on the discovery of vacuolar, granular, amoebic, or cystic forms in stool samples using wet mount smears, iodine staining, trichrome staining, or iron hematoxylin staining. The permanent staining methods provide more positive findings. However, mercuric chloride (HgCl(2))-based polyvinyl alcohol (PVA) and Schaudinn fixative are potentially toxic and dangerous to laboratory personnel and, as hazardous chemicals, present problems with disposal. METHODS: To determine whether in vitro culture could be an environmentally safe alternative, the culture growth of B. hominis in three commercially available liquid media (RPMI 1640, 199 Medium, and Dulbecco's modified Eagle's medium (DMEM)) were observed and compared. The sensitivity and specificity of these culture methods to identify B. hominis were compared with those of existing methods used clinically. RESULTS: Conditions for the anaerobic culture of B. hominis in these media were determined as follows: total inoculum sizes no less than 10(5) cells; pH values ranging from 7.0 to 7.5; concentrations of calf or horse serum ranging from 10% to 30% (vol/vol); basic antibiotics added; peaking times at days 3, 6, and 9 (pH 7.5) or days 4 and 8 (or 9) (pH 7.0) at 37 degrees C. No significant differences were noted in multiplication or generation times for the cultivation of B. hominis (p>0.05). In 56 of 398 positive cases, the short-term in vitro culture method achieved the best performance with regard to sensitivity and specificity of the five studied methods. CONCLUSIONS: With the advantages of environmental safety, convenience in preparation and storage, facility in morphologic discrimination, and outstanding performance in terms of sensitivity and specificity, the in vitro culture method could be applied to identify B. hominis for both clinical diagnosis and field study purposes. PMID- 22047716 TI - Nonrigid registration of CLSM images of physical sections with discontinuous deformations. AB - When biological specimens are cut into physical sections for three-dimensional (3D) imaging by confocal laser scanning microscopy, the slices may get distorted or ruptured. For subsequent 3D reconstruction, images from different physical sections need to be spatially aligned by optimization of a function composed of a data fidelity term evaluating similarity between the reference and target images, and a regularization term enforcing transformation smoothness. A regularization term evaluating the total variation (TV), which enables the registration algorithm to account for discontinuities in slice deformation (ruptures), while enforcing smoothness on continuously deformed regions, was proposed previously. The function with TV regularization was optimized using a graph-cut (GC) based iterative solution. However, GC may generate visible registration artifacts, which impair the 3D reconstruction. We present an alternative, multilabel TV optimization algorithm, which in the examined samples prevents the artifacts produced by GC. The algorithm is slower than GC but can be sped up several times when implemented in a multiprocessor computing environment. For image pairs with uneven brightness distribution, we introduce a reformulation of the TV-based registration, in which intensity-based data terms are replaced by comparison of salient features in the reference and target images quantified by local image entropies. PMID- 22047717 TI - 2D-Qsar for 450 types of amino acid induction peptides with a novel substructure pair descriptor having wider scope. AB - BACKGROUND: Quantitative structure-activity relationships (QSAR) analysis of peptides is helpful for designing various types of drugs such as kinase inhibitor or antigen. Capturing various properties of peptides is essential for analyzing two-dimensional QSAR. A descriptor of peptides is an important element for capturing properties. The atom pair holographic (APH) code is designed for the description of peptides and it represents peptides as the combination of thirty six types of key atoms and their intermediate binding between two key atoms. RESULTS: The substructure pair descriptor (SPAD) represents peptides as the combination of forty-nine types of key substructures and the sequence of amino acid residues between two substructures. The size of the key substructures is larger and the length of the sequence is longer than traditional descriptors. Similarity searches on C5a inhibitor data set and kinase inhibitor data set showed that order of inhibitors become three times higher by representing peptides with SPAD, respectively. Comparing scope of each descriptor shows that SPAD captures different properties from APH. CONCLUSION: QSAR/QSPR for peptides is helpful for designing various types of drugs such as kinase inhibitor and antigen. SPAD is a novel and powerful descriptor for various types of peptides. Accuracy of QSAR/QSPR becomes higher by describing peptides with SPAD. PMID- 22047718 TI - Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis. AB - BACKGROUND: Depression is associated with elevated levels of the inflammation marker C-reactive protein (CRP); yet, the direction of this association remains unclear. This study tested bi-directional longitudinal associations between CRP and depression in a sample of adolescents and young adults. The study compared the effect of current depression with the effect of cumulative episodes of depression over time. METHODS: Nine waves of data from the prospective population based Great Smoky Mountains Study (n = 1420) were used, covering children in the community aged 9 to 16, 19, and 21 years old. Structured interviews were used to assess depressive symptoms, depression diagnosis, and cumulative depressive episodes. Bloodspots were collected at each observation and assayed for CRP levels. RESULTS: CRP levels were not associated with later depression status. In contrast, all depression-related variables displayed evidence of association with later CRP levels. The associations with depressive symptoms and diagnostic status were attenuated after controlling for covariates, particularly body mass index, smoking, and medication use. The effect of cumulative depressive episodes, however, continued to be significant after accounting for a range of covariates. Body mass index, smoking behavior, and recent infections may mediate a portion of the effect of cumulative episodes on later CRP, but cumulative depressive episodes continued to predict CRP levels independently. CONCLUSIONS: The occurrence of multiple depressive episodes exerted the greatest effect on later CRP levels. This suggests that risk for the diseases of middle and old age- cardiovascular and metabolic disease--may begin in childhood and depend, in part, on long-term emotional functioning. PMID- 22047720 TI - Ordered mesoporous carbon coating on cordierite: synthesis and application as an efficient adsorbent. AB - Ordered mesoporous carbon coating on the honeycomb cordierite substrate has been prepared using low-polymerized phenolic resins as carbon sources and triblock copolymer F127 as the structure directing agent via the evaporation induced self assembly route. The high-resolution scanning electron microscopy (HRSEM), transmission electron microscopy (TEM), and nitrogen sorption techniques prove the hexagonally ordered pore arrays of carbon coating on the cordierite. The honeycomb monolith adsorbents coated by ordered mesoporous carbons are directly used without any activation, and exhibit adsorption capacities for chlorinated organic pollutants in water with 200 mg/g for p-chlorophenol and 178 mg/g for p chloroaniline (with respect to the net carbon coating), high adsorption ratio for low-concentration pollutants, large processing volumes and reusability. More than 200 repeated times can be achieved without obvious loss in both adsorption capacity and weight. PMID- 22047719 TI - Frontal white matter integrity predictors of adult alcohol treatment outcome. AB - BACKGROUND: Previous research has associated abnormalities in frontal lobe functioning with alcohol relapse. In this study, we used diffusion tensor imaging to investigate whether frontal white matter integrity measured at the start of treatment differs between persons with alcohol use disorders (AUD) who sustain treatment gains and those who return to heavy use after treatment. METHODS: Forty five treatment-seeking AUD inpatients and 30 healthy control subjects were included in the study. Six months after completing treatment, 16 of the AUD participants had resumed heavy use (RHU) and 29 others remained abstinent or drank minimally (treatment sustainers [TS]). Voxel-wise group comparisons (TS vs. RHU) were performed on fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity maps generated from each subject's diffusion tensor imaging scan at the start of treatment. RESULTS: We found significantly lower FA and significantly higher RD in the frontal lobes of the RHU group, relative to the TS group. The RHU group data are consistent with previous reports of abnormal frontal white matter tract abnormalities in persons with AUD. CONCLUSIONS: It is possible that the lower FA and higher RD in the RHU group reflect microstructural injury to frontal circuitries, and these may underlie the reduced cognitive control amid heightened reward sensitivity associated with resumption of heavy drinking. PMID- 22047721 TI - Enhancing uranium solubilization in soils by citrate, EDTA, and EDDS chelating amendments. AB - A systematic study was made of the effects of three soil amendments on the solubilization of uranium from a granitic soil. The aim was to optimize solubilization so as to enhance bioavailability for the purposes of remediation. The three amendments tested were with citrate, EDTA, and EDDS as chelating agents. The effects of pH, chelator concentration, and leaching time were studied. The most important factor in uranium solubilization was found to be the pH. In the absence of chelating agents, the greatest solubilization was obtained for alkaline conditions, with values representing about 15% of the total uranium activity in the bulk soil. There were major differences in uranium solubilization between the different amendments. The citrate treatment was the most efficient at acidic pH, particularly with the greatest concentration of citrate tested (50 mmol kg(-1)) after 6 days of treatment. Under these conditions, the uranium concentration in solution was greater by a factor of 356 than in the control suspension, and represented some 63% of the uranium concentration in the bulk soil. Under alkaline conditions, the EDTA and EDDS treatments gave the greatest uranium activity concentrations in solution, but these concentrations were much lower than those with the citrate amendment, and were not very different from the control results. The uranium extraction yield with EDDS amendment was greater than with EDTA. PMID- 22047722 TI - Hydrous ferric oxide-resin nanocomposites of tunable structure for arsenite removal: effect of the host pore structure. AB - Hydrous ferric oxide (HFO) loaded hybrid sorbents are considered to be excellent materials for arsenic removal from water. However, role of the host pore structure in the performance of the composites is still unclear. In the current study five HFO nanocomposites of similar HFO loadings (3.9-5.3% in Fe mass) were fabricated for arsenite removal, using self-synthesized polystyrene (PS) resins of similar particle sizes but different pore structures as hosts. Structure analysis demonstrated that the particle size of HFO aggregates decreased with decreasing pore size of PS. The adsorption of arsenite onto the nanocomposites with PS of smaller average pore size achieved equilibrium faster. Analysis of kinetic data with the intraparticle diffusion model demonstrated that arsenite adsorption onto PS-HFO nanocomposites with larger HFO particles was controlled by intraparticle diffusion whereas the limitation caused by intraparticle diffusion was weakened as the particle size of HFO decreased. The adsorption capacity of the hybrid adsorbents increased with decreased pore size of PS. These results indicated that the pore structure of the support materials would play a significant role in the performance of nanoparticle-loaded porous adsorbents. PMID- 22047723 TI - Synthesis of novel inorganic-organic hybrid materials for simultaneous adsorption of metal ions and organic molecules in aqueous solution. AB - In this paper, atom transfer radical polymerization (ATRP) and radical grafting polymerization were combined to synthesize a novel amphiphilic hybrid material, meanwhile, the amphiphilic hybrid material was employed in the absorption of heavy metal and organic pollutants. After the formation of attapulgite (ATP) ATRP initiator, ATRP block copolymers of styrene (St) and divinylbenzene (DVB) were grafted from it as ATP-P(S-b-DVB). Then radical polymerization of acrylonitrile (AN) was carried out with pendent double bonds in the DVD units successfully, finally we got the inorganic-organic hybrid materials ATP-P(S-b-DVB-g-AN). A novel amphiphilic hybrid material ATP-P(S-b-DVB-g-AO) (ASDO) was obtained after transforming acrylonitrile (AN) units into acrylamide oxime (AO) as hydrophilic segment. The adsorption capacity of ASDO for Pb(II) could achieve 131.6 mg/g, and the maximum removal capacity of ASDO towards phenol was found to be 18.18 mg/g in the case of monolayer adsorption at 30 degrees C. The optimum pH was 5 for both lead and phenol adsorption. The adsorption kinetic suited pseudo-second-order equation and the equilibrium fitted the Freundlich model very well under optimal conditions. At the same time FT-IR, TEM and TGA were also used to study its structure and property. PMID- 22047724 TI - Role of calcium oxide in sludge granulation and methanogenesis for the treatment of palm oil mill effluent using UASB reactor. AB - The granulation process in palm oil mill effluent using calcium oxide-cement kiln dust (CaO-CKD) provides an attractive and cost effective treatment option. In this study the efficiency of CaO-CKD at doses of 1.5-20 g/l was tested in batch experiments and found that 10 g of CaO/l caused the greatest degradation of VFA, butyrate and acetate. An upflow anaerobic sludge blanket (UASB) reactor was operated continuously at 35 degrees C for 150 days to investigate the effect of CaO-CKD on sludge granulation and methanogenesis during start-up. The treatment of POME emphasized the influence of varying organic loading rates (OLR). Up to 94.9% of COD was removed when the reactor was fed with the 15.5-65.5 g-CODg/l at an OLR of 4.5-12.5 kg-COD/m(3)d, suggesting the feasibility of using CaO in an UASB process to treat POME. The ratio of volatile solids/total solids (VS/TS) and volatile fatty acids in the anaerobic sludge in the UASB reactor decreased significantly after long-term operation due to the precipitation of calcium carbonate in the granules. Granulation and methanogenesis decreased with an increase in the influent CaO-CKD concentration. PMID- 22047725 TI - Relationship between sports participation and the level of motor coordination in childhood: a longitudinal approach. AB - OBJECTIVES: This study examined the stability of motor coordination and the relationship between motor coordination and organized sports participation over time. DESIGN: Longitudinal design. METHODS: A total of 371 children between six and nine years of age at initial testing completed a test battery measuring motor coordination in three consecutive years and a questionnaire on their club sports participation in year 1 and year 3 of testing. RESULTS: Correlation coefficients revealed the motor coordination of children to be a highly stable factor, ranging from 0.662 (6-8 years) to 0.873 (7-9 years). Results of the Repeated Measures ANOVA indicated that children who consistently practiced sports in a club environment over the three years of testing displayed better coordination levels than children who only partially participated or did not participate in a club environment at all. Moreover, stability was further indicated as consistent sports participation over time and changes or lack thereof did not substantially influence the development of motor coordination over time. In addition, the basic level of motor coordination and the amount of club sports participation significantly predicted sports participation two years later. CONCLUSION: The importance of the stability of motor coordination levels in childhood and its role in determining organized sports participation may have implications for talent identification purposes as well as potential health-related benefits in childhood and throughout the lifespan. PMID- 22047726 TI - Neural response to eye contact and paroxetine treatment in generalized social anxiety disorder. AB - Generalized social anxiety disorder (GSAD) is characterized by excessive fears of scrutiny and negative evaluation, but neural circuitry related to scrutiny in GSAD has been little studied. In this study, 16 unmedicated adults with GSAD and 16 matched healthy comparison (HC) participants underwent functional magnetic resonance imaging to assess neural response to viewed images of faces simulating movement into eye contact versus away from eye contact. GSAD patients were then treated for 8 weeks with paroxetine, and 15 patients were re-imaged. At baseline, GSAD patients had elevated neural response to eye contact in parahippocampal cortex, inferior parietal lobule, supramarginal gyrus, posterior cingulate and middle occipital cortex. During paroxetine treatment, symptomatic improvement was associated with decreased neural response to eye contact in regions including inferior and middle frontal gyri, anterior cingulate, posterior cingulate, precuneus and inferior parietal lobule. Both the magnitude of GSAD symptom reduction with paroxetine treatment and the baseline comparison of GSAD vs. HCs were associated with neural processing of eye contact in distributed networks that included regions involved in self-referential processing. These findings demonstrate that eye contact in GSAD engages neurocircuitry consistent with the heightened self-conscious emotional states known to characterize GSAD patients during scrutiny. PMID- 22047727 TI - Tianeptine reverses stress-induced asymmetrical hippocampal volume and N acetylaspartate loss in rats: an in vivo study. AB - Stress-induced hippocampal volume loss and decrease in N-acetylaspartate (NAA) level have been reported to be associated with impaired neural plasticity and neuronal damage in adults. Accordingly, reversing structural and metabolite damage in the hippocampus may be a desirable goal for antidepressant therapy. The present study investigated the effects of tianeptine on chronic stress-induced hippocampal volume loss and metabolite alterations in vivo in 24 Sprague-Dawley rats. Rats were subjected to a consecutive 28-day forced swimming test stress. Tianeptine (50mg/kg) or saline was administered intragastrically 4h after swimming each day. Spontaneous behaviors, serum corticosterone concentration, hippocampal volume and NAA level were evaluated after stress. Chronic tianeptine treatment counteracted the chronic stress-induced suppression of spontaneous behaviors, elevated serum corticosterone concentration, reduced hippocampal volume and decreased NAA level. Moreover, we found asymmetrical right-left hippocampal volume loss in stressed rats, with the left hippocampus more sensitive to chronic stress than the right hippocampus. In addition, stressed rats showed a decreased level of hippocampal metabolites, without significant loss of hippocampal volume. These findings provide experimental evidence for impaired structural plasticity of the brain being an important feature of depressive illness and suggest that prophylactic tianeptine treatments could reverse structural changes in brain. The structural and neurochemical alterations in the hippocampus may be valuable indexes for evaluating the prophylactic and curative effect of antidepressant treatments in depressive and stress-related disorders. PMID- 22047729 TI - Detecting abnormalities of corpus callosum connectivity in autism using magnetic resonance imaging and diffusion tensor tractography. AB - The corpus callosum (CC) has emerged as one of the primary targets of autism research. To detect aberrant CC interhemispheric connectivity in autism, we performed T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI)-based tractography in 18 children with high functioning autism (HFA) and 16 well-matched typically developing (TD) children. We compared global and regional T1 measures (CC volume, and CC density), and the DTI measures [fractional anisotropy (FA), apparent diffusion coefficient (ADC), average fiber length (AFL), and fiber number (FN)] of transcallosal fibers, between the two groups. We also evaluated the relationships between scores on the Childhood Autism Rating Scale (CARS) and CC T1 or DTI measurements. Significantly less white matter density in the anterior third of the CC, and higher ADC and lower FN values of the anterior third transcallosal fiber tracts were found in HFA patients compared to TD children. These results suggested that the anterior third CC density and transcallosal fiber connectivity were affected in HFA children. PMID- 22047728 TI - Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: association with allelic variation in GABRA2 and BDNF. AB - Offspring from families with multiple cases of alcohol dependence have a greater likelihood of developing alcohol dependence (AD) and related substance use disorders. Greater susceptibility for developing these disorders may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing and AD susceptibility. We examined the cerebellum of 71 adolescent/young adult high-risk (HR) offspring from families with multiple cases of alcohol dependence (multiplex families), and 60 low-risk (LR) controls with no family history of alcohol or drug dependence who were matched for age, gender, socioeconomic status and IQ, with attention given to possible effects of personal use of substances and maternal use during pregnancy. Magnetic resonance images were acquired on a General Electric 1.5 Tesla scanner and manually traced (BRAINS2) blind to clinical information. GABRA2 and BDNF variation were tested for their association with cerebellar volumes. High-risk offspring from multiplex AD families showed greater total volume of the cerebellum and total gray matter (GM), in comparison with LR controls. An interaction between allelic variation in GABRA2 and BDNF genes was associated with GM volumes, suggesting that inherited variation in these genes may promote early developmental differences in neuronal proliferation of the cerebellum. PMID- 22047730 TI - Reduced amygdala-orbitofrontal connectivity during moral judgments in youths with disruptive behavior disorders and psychopathic traits. AB - We used functional magnetic resonance imaging (fMRI) to investigate dysfunction in the amygdala and orbitofrontal cortex in adolescents with disruptive behavior disorders and psychopathic traits during a moral judgment task. Fourteen adolescents with psychopathic traits and 14 healthy controls were assessed using fMRI while they categorized illegal and legal behaviors in a moral judgment implicit association task. fMRI data were then analyzed using random-effects analysis of variance and functional connectivity. Youths with psychopathic traits showed reduced amygdala activity when making judgments about legal actions and reduced functional connectivity between the amygdala and orbitofrontal cortex during task performance. These results suggest that psychopathic traits are associated with amygdala and orbitofrontal cortex dysfunction. This dysfunction may relate to previous findings of disrupted moral judgment in this population. PMID- 22047732 TI - Analytical metrological characterization of the three-parameter sine fit algorithm. AB - The three-parameter sine fit is a well known algorithm used in IEEE standard 1241 2000 for ADC characterization to estimate sine wave parameters from recorded data. An analytical metrological characterization of that algorithm is carried out in terms of its design parameters, namely the sampling rate and the number of samples. Optimal and sub-optimal parameters' sets are found. Focusing on the amplitude estimation, an approximated statistical characterization of the second order is given in the most general case of zero mean additive noise, whereas the exact probability density function is found for the optimal set of algorithm parameters in the case of additive white Gaussian noise. In this particular case, the frequency behavior of the algorithm is fully analyzed and the exact frequency response of the amplitude is also found. An approximated expression that is easier to use is then presented and discussed. Simulation results for a single set of parameters are presented in order to graphically illustrate the analytical results. PMID- 22047731 TI - Prefrontal hypoactivation during cognitive control in early abstinent methamphetamine-dependent subjects. AB - Individuals who abuse methamphetamine (MA) perform at levels below those of healthy controls on tests that require cognitive control. As cognitive control deficits may influence the success of treatment for addiction, we sought to help clarify the neural correlates of this deficit. MA-dependent (n=10, abstinent 4-7 days) and control subjects (n=18) performed a color-word Stroop task, which requires cognitive control, during functional MRI (fMRI). The task included a condition in which participants were required to respond to one stimulus dimension while ignoring another conflicting dimension, and another condition without conflict. We compared the groups on performance and neural activation in the two conditions. MA-dependent subjects made more errors and responded more slowly than controls. Controlling for response times in the incongruent condition, voxel-wise mixed effects analyses (whole-brain corrected) demonstrated that MA-dependent subjects had less activation than control subjects in the right inferior frontal gyrus, supplementary motor cortex/anterior cingulate gyrus and the anterior insular cortex during the incongruent condition only. MA-dependent subjects did not exhibit greater activation in any brain region in either of the Stroop conditions. These preliminary findings suggest that hypofunction in cortical areas that are important for executive function underlies cognitive control deficits associated with MA dependence. PMID- 22047733 TI - Synthesis of near-IR fluorescent oxazine dyes with esterase-labile sulfonate esters. AB - Near-IR oxazine dyes are reported that contain sulfonate esters which are rapidly cleaved by esterase activity to unmask highly polar anionic sulfonates. Strategies for the synthesis of these dyes included the development of milder dye condensation conditions with improved functional compatibility and the use of an alkyl halide that allows for the introduction of esterase-labile sulfonates without the need for sulfonation of the target molecule. PMID- 22047735 TI - IL-37: a new anti-inflammatory cytokine of the IL-1 family. AB - The IL-1 family of cytokines encompasses eleven proteins that each share a similar beta-barrel structure and bind to Ig-like receptors. Some of the IL-1 like cytokines have been well characterised, and play key roles in the development and regulation of inflammation. Indeed, IL-1alpha (IL-1F1), IL-1beta (IL-1F2), and IL-18 (IL-1F4) are well-known inflammatory cytokines active in the initiation of the inflammatory reaction and in driving Th1 and Th17 inflammatory responses. In contrast, IL-1 receptor antagonist (IL-1Ra, IL-1F3) and the receptor antagonist binding to IL-1Rrp2 (IL-36Ra, IL-1F5) reduce inflammation by blocking the binding of the agonist receptor ligands. In the case of IL-37 (IL 1F7), of which five different splice variants have been described, less is known of its function, and identification of the components of a heterodimeric receptor complex remains unclear. Some studies suggest that IL-37 binds to the alpha chain of the IL-18 receptor in a non-competitive fashion, and this may explain some of the disparate biological effects that have been reported for mice deficient in the IL-18R. The biological properties of IL-37 are mainly those of down regulating inflammation, as assessed in models where human IL-37 is expressed in mice. In this review, an overview of the role of IL-37 in the regulation of inflammation is presented. The finding that IL-37 also locates to the nucleus, as do IL-1alpha and IL-33, for receptor-independent organ/tissue-specific regulation of inflammation is also reviewed. PMID- 22047736 TI - [Histological and immunohistochemical profile of sporadic and familial medullary thyroid carcinoma]. AB - INTRODUCTION: The histological and immunohistochemical profile of medullary thyroid carcinoma is ill-defined. The objective of this study was to determine the epidemiological, histological, and immunohistochemical characteristics of medullary carcinoma and to analyze whether differences exist between sporadic and familial carcinomas. PATIENTS AND METHODS: Fifty-five histologically confirmed tumors were studied. Histological slides were reviewed and immunohistochemical staining of the archival paraffin blocks was performed. RESULTS: Nineteen of the 55 carcinomas (35%) were sporadic, and 36 (65%) familial. Sex distribution was similar, but familial carcinoma was more common in patients under 40 years of age (p<0.001). A solid growth pattern and plasmacytoid cells were found in most cases. C-cell hyperplasia and multicentricity were more frequent findings in familial carcinoma, while tumor necrosis, hemorrhagic foci, vascular invasion, and neovascularization were more common in the sporadic type. Immunohistochemical staining was positive for calcitonin, CEA, bcl-2, and p53 protein. With regard to staging, familial carcinomas were diagnosed in the earliest stages, when they were smaller and there were no lymph node metastases (p<0.01). CONCLUSIONS: Familial cases were more frequent when there was more C-cell hyperplasia and multicentricity. Sporadic cases more frequently showed foci of necrosis, hemorrhage, vascular invasion, and neovascularization. Neither histopathological nor immunohistochemical criteria are useful for differentiating between familial and sporadic forms. PMID- 22047737 TI - Local to regional scale industrial heavy metal pollution recorded in sediments of large freshwater lakes in central Europe (lakes Geneva and Lucerne) over the last centuries. AB - This research first focuses on the spatial and temporal patterns of heavy metals from contrasting environments (highly polluted to deepwater sites) of Lake Geneva. The mercury (Hg) and lead (Pb) records from two deepwater sites show that the heavy metal variations before the industrial period are primarily linked to natural weathering input of trace elements. By opposition, the discharge of industrial treated wastewaters into Vidy Bay of Lake Geneva during the second part of the 20th century, involved the sedimentation of highly metal-contaminated sediments in the area surrounding the WWTP outlet pipe discharge. Eventually, a new Pb isotope record of sediments from Lake Lucerne identifies the long-term increasing anthropogenic lead pollution after ca. 1500, probably due to the development of metallurgical activities during the High Middle Ages. These data furthermore allows to compare the recent anthropogenic sources of water pollution from three of the largest freshwater lakes of Western Europe (lakes Geneva, Lucerne, and Constance). High increases in Pb and Hg highlight the regional impact of industrial pollution after ca. 1750-1850, and the decrease of metal pollution in the 1980s due to the effects of remediation strategies such as the implementation of wastewater treatment plants (WWTPs). However, at all the studied sites, the recent metal concentrations remain higher than pre-industrial levels. Moreover, the local scale pollution data reveal two highly contaminated sites (>100 MUg Pb/g dry weight sediment) by industrial activities, during the late-19th and early-20th centuries (Lake Lucerne) and during the second part of the 20th century (Vidy Bay of Lake Geneva). Overall, the regional scale pollution history inferred from the three large and deep perialpine lakes points out at the pollution of water systems by heavy metals during the last two centuries due to the discharge of industrial effluents. PMID- 22047738 TI - Isotopic signatures for natural versus anthropogenic Pb in high-altitude Mt. Everest ice cores during the past 800 years. AB - A long-term record, extending back 800 years (1205 to 2002 AD), of the Pb isotopic composition ((206)Pb/(207)Pb and (208)Pb/(207)Pb) as well as Pb concentrations from high altitude Mt. Everest ice cores has the potential to identify sources and source regions affecting natural and anthropogenic Pb deposition in central Asia. The results show that the regional natural background Pb isotope signature (~1.20 for (206)Pb/(207)Pb and ~2.50 for (208)Pb/(207)Pb) in the central Himalayas was dominated by mineral dust over the last ~750 years from 1205 to 1960s, mostly originating from local sources with occasional contributions of long-range transported dust probably from Sahara desert and northwestern India. Since the 1970s, the Pb isotope ratios are characterized by a continuous decline toward less radiogenic ratios with the least mean ratios of 1.178 for (206)Pb/(207)Pb and 2.471 for (208)Pb/(207)Pb in the period 1990-1996. The depression of the (206)Pb/(207)Pb and (208)Pb/(207)Pb values during the corresponding periods is most likely due to an increasing influence of less radiogenic Pb of anthropogenic origin mainly from leaded gasoline used in South Asia (India as well as possibly Bangladesh and Nepal). From 1997 to 2002, isotopic composition tends to show a shift to slightly more radiogenic signature. This is likely attributed to reducing Pb emissions from leaded gasoline in source regions, coinciding with the nationwide reduction of Pb in gasoline and subsequent phase-out of leaded gasoline in South Asia since 1997. An interesting feature is the relatively high levels of Pb concentrations and enrichment factors (EF) between 1997 and 2002. Although the reason for this feature remains uncertain, it would be probably linked with an increasing influence of anthropogenic Pb emitted from other sources such as fossil fuel combustion and non-ferrous metal production. PMID- 22047739 TI - Daily urinary excretion of uranium in members of the public of Southwest Nigeria. AB - The main aim of this study was to determine and evaluate urinary excretion values of uranium in members of the public of Southwest Nigeria living in areas of low environmental uranium. As several uranium mines are running in Nigeria and the operations could be a risk of contamination for the workers as well as for the members of the public, biomonitoring of urine could provide information about the exposure to uranium for the subjects. Therefore, baseline values of uranium in urine are needed from subjects living in areas without mining activities. Volunteers of both genders (age range 3 to 78 years) were asked to collect 24h urine samples. The concentration measurements of uranium in urine were performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). In addition, urinary creatinine values were determined for normalization of the renal uranium relative to the creatinine concentrations. The urinary uranium concentrations and their creatinine normalized values ranged from <10.4 to 150 ng L(-1) (median 13.8 ng L( 1)) and from 2.52 to 252.7 ng g(-1) creatinine (median 33.4 ng g(-1) creatinine), respectively, for adult subjects above 15 years of both genders. An increased uranium excretion value of 61.6 ng L(-1) (median), and of 76.0 ng g(-1) creatinine, respectively, were found in young subjects below 15 years. The median of daily excreted uranium was estimated to be 14.2 ng d(-1) for adults and of 45.1 ng d(-1) for children, respectively. The uranium excretion from males and females living in Nigeria in a non-mining area was comparable to reference values reported from other countries with low level of environmental uranium. The data can be considered as baseline values of urinary uranium in unexposed subjects in Nigeria. PMID- 22047740 TI - Informational needs of gynecologic cancer survivors. AB - OBJECTIVES: In preparation for the launch of a gynecologic oncology survivorship program, this study looked at the informational needs of women with gynecologic cancers. Although studies have touched on some of these needs, no published literature has investigated the comprehensive informational needs of gynecologic oncology patients within all sites of gynecologic cancers. METHODS: A needs assessment, consisting of a self-administered questionnaire, was conducted at an ambulatory gynecologic oncology clinic from August 2010 to March 2011. This study investigated the informational needs of patients, including the importance of information, the amount desired, and the preferred mode of delivery. Informational needs were grouped into six domains: medical, practical, physical, emotional, social, and spiritual. RESULTS: 185 surveys were analyzed and the majority of the respondents were Caucasian (77%) and over the age of 50 (66%). Forty-nine percent of respondents were diagnosed with ovarian cancer, and there was an even distribution between newly diagnosed patients (38%), those in long term follow-up (27%), and those with recurrent disease (37%). Overall, respondents placed more importance on receiving medical information (P<0.01). The three preferred education modalities were; pamphlets, one-on-one discussions with health care professionals and websites. Age, education, and disease site were associated with differing informational needs. CONCLUSIONS: This study has highlighted the most important informational needs of patients with gynecologic malignancies in our patient population. This information may guide the development of clinical survivorship programs and educational resources for patients in the future. PMID- 22047741 TI - Physical and chemical effects of ingested plastic debris on short-tailed shearwaters, Puffinus tenuirostris, in the North Pacific Ocean. AB - We investigated the plastics ingested by short-tailed shearwaters, Puffinus tenuirostris, that were accidentally caught during experimental fishing in the North Pacific Ocean in 2003 and 2005. The mean mass of plastics found in the stomach was 0.23 g per bird (n=99). Plastic mass did not correlate with body weight. Total PCB (sum of 24 congeners) concentrations in the abdominal adipose tissue of 12 birds ranged from 45 to 529 ng/g-lipid. Although total PCBs or higher-chlorinated congeners, the mass of ingested plastic correlated positively with concentrations of lower-chlorinated congeners. The effects of toxic chemicals present in plastic debris on bird physiology should be investigated. PMID- 22047742 TI - Childhood maltreatment in South Korea: retrospective study. AB - OBJECTIVE: This study explored the prevalence of childhood maltreatment in South Korea using the retrospective version of ICAST and the associations between perceptions of abuse experienced during childhood and recent interpersonal problems and depression. METHODS: 539 young persons, aged 18-24 years, from various universities, work places, and clinical settings participated in a study using the ISPCAN Child Abuse Screening Tool-Retrospective Version (ICAST-R), the short form of the Korean-Inventory of Interpersonal Problems Circumplex Scale (KIIP-SC), and the Korean version of the Beck Depression Inventory (K-BDI). RESULTS: While males reported more physical abuse, females reported being exposed to more emotional or sexual abuse. The proportion of reported extra-familial or peer abuse was relatively high. Interpersonal problems and depression were significantly high for those who experienced all types of abuse during childhood. Perception of physical abuse as reasonable/justified discipline affected interpersonal problems and perception of emotional abuse when compared to peers affected interpersonal problems and depression. Unlike previous studies, this study identified more depressive symptoms reported with disclosure of sexual abuse. PRACTICE IMPLICATIONS: These findings highlight the importance of understanding how one perceives maltreatment. Perceiving an abusive act as a justifiable disciplinary method may affect reporting as well as longer term consequences for the victim. A wide range of perpetrators and different settings in which maltreatment may occur must be considered as influencing these perceptions. This study contributed to the determination of validity of the ICAST R for use in wider population surveys. PMID- 22047743 TI - Adhesion and hemifusion of cytoplasmic myelin lipid membranes are highly dependent on the lipid composition. AB - We report the effects of calcium ions on the adhesion and hemifusion mechanisms of model supported myelin lipid bilayer membranes of differing lipid composition. As in our previous studies Min et al. [1,2], the lipid compositions used mimic "healthy" and "diseased-like" (experimental autoimmune encephalomyelitis, EAE) membranes. Our results show that the interaction forces as a function of membrane separation distance are well described by a generic model that also (and in particular) includes the hydrophobic interaction arising from the hydrophobically exposed (interior) parts of the bilayers. The model is able to capture the mechanical instability that triggers the onset of the hemifusion event, and highlights the primary role of the hydrophobic interaction in membrane fusion. The effects of lipid composition on the fusion mechanism, and the adhesion forces between myelin lipid bilayers, can be summarized as follows: in calcium-free buffer, healthy membranes do not present any signs of adhesion or hemifusion, while diseased membranes hemifuse easily. Addition of 2mM calcium favors adhesion and hemifusion of the membranes independently of their composition, but the mechanisms involved in the two processes were different: healthy bilayers systematically presented stronger adhesion forces and lower energy barriers to fusion compared to diseased bilayers. These results are of particular relevance for understanding lesion development (demyelination, swelling, vacuolization and/or vesiculation) in myelin associated diseases such as multiple sclerosis and its relationship to lipid domain formation in myelin membranes. PMID- 22047744 TI - The protective effects of plasma gelsolin on stroke outcome in rats. AB - BACKGROUND: To date, recombinant tissue plasminogen activator (rtPA) is the only approved drug for ischemic stroke. It is intravenously administered functioning as a thrombolytic agent and is used to obtain reperfusion of the affected area of the brain. Excitotoxicity, inflammation and apoptosis are all involved in delayed neuronal death following stroke and offer multiple opportunities to intervene with neuroprotective agents. Gelsolin (GSN) is an actin- and calcium-binding protein mediating the disassembly of actin filaments and activity of calcium channels. It also functions as a regulator of apoptosis and inflammatory responses. This study tests the hypothesis that increasing the concentration of the form of GSN known as plasma GSN (pGSN) near an infarct will provide neuroprotection following ischemic stroke. METHODS: We induced middle cerebral artery occlusion (MCAO) in male rats via intracranial injection of endothelin-1 (ET-1), a potent vasoconstrictor, and then treated with local delivery of pGSN. Whole brain laser Doppler perfusion imaging was performed through the skull to assess MCAO effectiveness. Cylinder and vibrissae tests evaluated sensorimotor function before and 72 h after MCAO. Infarct volumes were examined 72 h after MCAO via 2, 3, 5-triphenyltetrazolium chloride (TTC) assay. RESULTS: Estimates of relative cerebral perfusion were significantly decreased in all groups receiving MCAO with no differences detected between treatments. Despite equivalent initial strokes, the infarct volume of the pGSN treatment group was significantly reduced compared with the untreated MCAO rats at 72 h. ET-1 induced significant deficits in both cylinder and vibrissae tests while pGSN significantly limited these deficits. CONCLUSION: Gelsolin could be a promising drug for protection against neurodegeneration following ischemic stroke. PMID- 22047745 TI - [Ultrasonography for hand surgeons (lecture from the 46th meeting of French Society of Hand Surgery)]. AB - Ultrasound examination is inexpensive, easily accessible and has numerous applications. Its diagnostic or even therapeutic use is developing in the context of hand surgery. The purpose of this work is to review the literature dealing with hand ultrasonograpy by recalling its physical basis and by showing the normal and pathological aspects of different structures and pathologies. PMID- 22047746 TI - The use of N,N'-diallylaldardiamides as cross-linkers in xylan derivatives-based hydrogels. AB - N,N'-Diallylaldardiamides (DA) were synthesized from galactaric, xylaric, and arabinaric acids, and used as cross-linkers together with xylan (X) derivatives to create new bio-based hydrogels. Birch pulp extracted xylan was derivatized to different degrees of substitution of 1-allyloxy-2-hydroxy-propyl (A) groups combined with 1-butyloxy-2-hydroxy-propyl (B) and/or hydroxypropyl (HP) groups. The hydrogels were prepared in water solution by UV induced free-radical cross linking polymerization of derivatized xylan polymers without DA cross-linker (xylan derivative hydrogel) or in the presence of 1 or 5 wt% of DA cross-linker (DA hydrogel). Commercially available cross-linker (+)-N,N'-diallyltartardiamide (DAT) was also used. The degree of substitution (DS) of A, B, and HP groups in xylan derivatives was analyzed according to (1)H NMR spectra. The DS values for the cross-linkable A groups of the derivatized xylans were 0.4 (HPX-A), 0.2 (HPX BA), and 0.4 (X-BA). The hydrogels were examined with FT-IR and elemental analysis which proved the cross-linking successful. Water absorption of the hydrogels was examined in deionized water. Swelling degrees up to 350% were observed. The swollen morphology of the hydrogels was assessed by scanning electron microscopy (SEM). The presence of cross-linkers in DA hydrogels had only a small impact on the water absorbency when compared to xylan derivative hydrogels but a more uniform pore structure was achieved. PMID- 22047747 TI - Synthesis of water-soluble multidentate aminoalcohol beta-cyclodextrin derivatives via epoxide opening. AB - New highly soluble beta-aminoalcohol beta-cyclodextrin (beta-CD) derivatives have been synthesized via nucleophilic epoxide opening reactions with mono-6-amino mono-6-deoxy-permethyl-beta-CD and mono-6-amino mono-6-deoxy-beta-CD. The binding properties of the beta-CD were enhanced by linking aminoalcohol subunits which caused its solubility to improve markedly. The reaction conditions were optimised using microwave irradiation giving moderate-to-good yields with a series of epoxides. A regioselective epoxide opening reaction was observed in the reaction with styrene oxide while the stereoselectivity was strictly dependent on substrate structure. PMID- 22047748 TI - Mice spermatogonial stem cells transplantation induces macrophage migration into the seminiferous epithelium and lipid body formation: high-resolution light microscopy and ultrastructural studies. AB - Transplantation of spermatogonial stem cells (SSCs), the male germline stem cells, in experimental animal models has been successfully used to study mechanisms involved in SSC self-renewal and to restore fertility. However, there are still many challenges associated with understanding the recipient immune response for SSCs use in clinical therapies. Here, we have undertaken a detailed structural study of macrophages elicited by SSCs transplantation in mice using both high-resolution light microscopy (HRLM) and transmission electron microscopy (TEM). We demonstrate that SSCs transplantation elicits a rapid and potent recruitment of macrophages into the seminiferous epithelium (SE). Infiltrating macrophages were derived from differentiation of peritubular monocyte-like cells into typical activated macrophages, which actively migrate through the SE, accumulate in the tubule lumen, and direct phagocytosis of differentiating germ cells and spermatozoa. Quantitative TEM analyses revealed increased formation of lipid bodies (LBs), organelles recognized as intracellular platforms for synthesis of inflammatory mediators and key markers of macrophage activation, within both infiltrating macrophages and Sertoli cells. LBs significantly increased in number and size in parallel to the augmented macrophage migration during different times post-transplantation. Our findings suggest that LBs may be involved with immunomodulatory mechanisms regulating the seminiferous tubule niche after SSC transplantation. PMID- 22047749 TI - Fingermark detection on non-porous and semi-porous surfaces using YVO4:Er,Yb luminescent upconverting particles. AB - This article describes the use of an anti-Stokes luminescent material (upconverter), yttrium vanadate doped with ytterbium and erbium (YVO(4):Er,Yb), for the development of latent fingermarks on a range of non-porous surfaces. Anti Stokes luminescent materials emit light at shorter wavelengths than the excitation wavelength. This property is unusual in both natural and artificial materials commonly found as exhibits in forensic science casework. As a result, fingermark detection techniques based on anti-Stokes luminescence are potentially extremely sensitive and selective. Latent fingermarks on non-luminescent and inherently luminescent substrates, including Australian polymer banknotes (a well known 'difficult' surface), were developed with YVO(4):Er,Yb by dry powder and wet powder techniques. The effectiveness of YVO(4):Er,Yb for fingermark detection was compared with that of cyanoacrylate fuming and of sodium yttrium tetrafluoride doped with ytterbium and erbium (NaYF(4):Er,Yb). The results illustrate some benefit of luminescent up-converting phosphors over traditional luminescence techniques for the detection of latent fingermarks. PMID- 22047750 TI - Anabolic androgenic steroids abuse and cardiac death in athletes: morphological and toxicological findings in four fatal cases. AB - Anabolic androgenic steroids (AAS) are the main class of doping agents and their consumption produces adverse effects involving several organs and systems. Three cases of sudden cardiac death (SCD) and one of death due to congestive heart failure of previously healthy athletes who were AAS users are herein reported. Concentric cardiac hypertrophy with focal fibrosis (one case), dilated cardiomyopathy with patchy myocyte death (two cases) and eosinophilic myocarditis (one case) were observed and most probably relate to the final event. Molecular investigation for viral genomes was positive in one case (Ebstein virus). Our data confirm previous findings, showing that the most typical cardiac abnormality in AAS abusers is left ventricular hypertrophy, associated with fibrosis and myocytolysis. An exceptional cardiovascular substrate was represented by the case with drug induced eosinophilic myocarditis. These features are at risk of ventricular arrhythmias as well as congestive heart failure. The cause-effect relationship between AAS abuse and cardiac death can be established only by a rigorous methodology with the use of standardized protocols, including precise morphological studies of all target organs to search for chronic toxic effects. Laboratory investigations should focus on AAS searching on a wide range of biological matrices to demonstrate type, magnitude and time of exposure. PMID- 22047751 TI - Screening of gunshot residues using desorption electrospray ionisation-mass spectrometry (DESI-MS). AB - Several studies have indicated that there are potential environmental sources of particles resembling inorganic primer found in gunshot residues (GSR); as a consequence examiners are reluctant to unambiguously assign the origin of inorganic particles. If organic gunshot residues (OGSR) were found in combination with inorganic particles, the possibility of environmental sources could be potentially eliminated, thereby significantly enhancing the strength of the evidence. Methods have been previously described whereby GSR specimens can be analysed for the presence of OGSR or inorganic GRS (IGSR). However, no methods have been reported that allow the analysis of both OGSR and IGSR on the same specimen. Described in this article is a direct method using desorption electrospray ionisation-mass spectrometry (DESI-MS) for the detection of methyl centralite (MC), ethyl centralite (EC) and diphenylamine (DPA) on adhesive tape GSR stubs typically used for scanning electron microscopy-energy-dispersive X-ray (SEM-EDX) analysis. The optimisation of numerous parameters was conducted using an experimental design. The results indicate that direct analysis of these organic components of GSR is possible although some limitations were also identified. This initial investigation has also indicated that subjecting stubs to DESI analysis does not interfere with subsequent SEM-EDX analysis of primer residues; therefore the technique described herein allows a comprehensive examination of GSR that would be highly probative in the event that both OGSR and IGSR are detected in the same specimen. PMID- 22047752 TI - Simultaneous detection of seventeen drugs of abuse and metabolites in hair using solid phase micro extraction (SPME) with GC/MS. AB - INTRODUCTION: The analysis of pediatric and adult hair is a useful non-invasive biomarker to effectively detect long term exposure to various xenobiotics, specifically drugs of abuse such as cocaine, opiates and amphetamines. Very often individuals are using, or are exposed to multiple drugs simultaneously and therefore it is important to be able to detect them in the same analysis. We have developed a sensitive and specific solid phase micro extraction (SPME) coupled with gas chromatography mass spectrometry (GC/MS) to detect 17 different analytes in hair using a single extraction method. METHOD: Five milligrams of hair is extracted overnight, subjected to solid phase extraction (SPE) and then to SPME GC/MS. The aimed analytes include amphetamine, methamphetamine, MDA, MDMA, cocaine, benzoylecognine, norcocaine, cocaethylene, methadone, codeine, morphine, 6-AM, oxycodone, oxymorphone, hydrocodone, hydromorphone and meperidone. RESULTS: The following are the LOD of the various drugs: 0.2ng/mg hair for amphetamine, methamphetamine, MDA, MDMA, morphine, codeine, 6-AM, oxycodone, oxymorphone, hydromorphone, hydrocodone, meperidine and 0.13ng/mg hair for cocaine, benzoylecognine, cocaethylene, norcocaine and methadone. CONCLUSION: This GC/MS method is sensitive and specific to detect the presence of these 17 analytes in as little as 5mg of hair and is especially useful for newborn and child hair analysis where the amount of hair is often very limited. PMID- 22047753 TI - Short term outcomes after cardiac surgery in a Jehovah's Witness population: an institutional experience. AB - BACKGROUND: Minimising blood transfusion has a number of medical and logistical benefits, and is of particular importance for followers of the Jehovah's Witness faith. We examined the short term outcomes in this group of patients based on our institutional practice over the past decade. PATIENTS/METHODS: Data on 59 patients (73% male, mean age 66 years [range 40-83]) who identified as Jehovah's Witness was prospectively collected and retrospectively analysed from a systematised database over the period from January 1999 to June 2010. Mean logistic Euroscore was 4.5, with coronary artery bypass procedures most common (44/59, 75%) followed by aortic valve replacement (6/59, 10%). RESULTS: Average haemoglobin (Hb) fell from 142 g/L preoperatively to 109 g/L at discharge. Output from cardiac drains was reduced in patients who received aprotinin (34/59, 58%, p=0.05) compared to tranexaemic acid (11/59, 18%) or no antifibrinolytic (15/59, 25%). Operative mortality was 1/59 (1.7%) with an average length of postoperative stay of 6.2 days. Morbidity rates for neurologic deficit 2/59 (3.4%), deep sternal infection 1/59 (1.7%) and postoperative myocardial infarction 1/59 (1.7%) were within accepted ranges. CONCLUSION: Cardiac surgery can be performed safely in Jehovah's Witness patients with acceptable outcomes. PMID- 22047754 TI - Reverse contrast and substructures in protein micro-patterns on 3D polymer surfaces. AB - We characterize an approach enabling protein patterning over broad polymer areas based on selective protein adsorption on surfaces of spin-cast amino-terminated polystyrene structured topographically with elastomer molds (capillary force lithography) and passivated locally against adsorption with poly(ethylene oxide) silanes printed with flat elastomer stamps (inverted micro-contact printing). Atomic force microscopy reveals uniformity of PS-NH(2) films with stripes of grooves and elevations alternating with periodicity 43 MUm) or narrow ridges, respectively. Reverse contrast in protein micro patterns is induced by modified relief geometry, which affects surface flux of silanes from stamp to polymer surface both within and away from contact zones of micro-contact printing. In addition, protein substructures with a fraction lambda/n of relief periodicity are observed on surfaces with elevated ridges (n=2) and plateaus (n=2 and 4). This is due to the locally modified protein adsorption with silane concentration and surface topography, respectively. PMID- 22047755 TI - Risk assessment models for thromboprophylaxis of medical patients. PMID- 22047756 TI - Lack of effect of moderate-duration static stretching on plantar flexor force production and series compliance. AB - BACKGROUND: The effects of an acute bout of moderate-duration static stretching on plantar flexor force production, series compliance of the muscle-tendon unit, and levels of neuromuscular activation were examined. METHODS: Eighteen active individuals (9 men and 9 women) performed four 45-s static plantar flexor stretches and a time-matched control of no stretch (where subjects remained seated in the dynamometer for 4 min with no stretch being performed). Measures of peak isometric moment, rate of force development, neuromuscular activation (interpolated twitch technique and electromyography), twitch force characteristics, passive moment during stretch, and tendon elongation during maximal voluntary contractions were taken before and after the stretching. FINDINGS: Despite a significant stress-relaxation response during stretch (9.3%, P<0.01) there were no significant differences in peak isometric moment (P=0.35; effect size 0.13), rate of force development (P=0.93; effect size 0.01), neuromuscular activation (interpolated twitch: P=0.86; electromyography: P=0.09; effect size 0.02), or tendon elongation (P=0.61; effect size 0.07) after stretching. Twitch characteristics were also unchanged after stretching, although there was a reduction in the rate of twitch torque relaxation (RR(t); P<0.01). INTERPRETATION: The acute bout of moderate-duration static stretching did not impair the force generating capacity of the plantar flexors or negatively affect muscle-tendon mechanical properties. Static stretching may not always have detrimental consequences for force production. Thus, clinicians may be able to apply moderate-duration stretches to patients without risk of reducing muscular performance. PMID- 22047757 TI - Risk factors for venous thromboembolism in critically ill trauma patients who cannot receive chemical prophylaxis. AB - BACKGROUND: Standard venous thromboembolism (VTE) prevention for critically ill trauma patients includes sequential compression devices and chemical prophylaxis. When contraindications to anticoagulation are present, prophylactic inferior vena cava filters (IVCF) may be used to prevent pulmonary emboli (PE) in high-risk patients, but specific indications are lacking. We sought to identify independent predictors of VTE in critically-ill trauma patients who cannot receive chemical prophylaxis in order to identify a subset of patients who may benefit from aggressive screening and/or prophylactic IVCF placement. METHODS: All trauma patients in the surgical ICU from 2008 to 2009 were prospectively followed. Patients with an ICU length of stay >=2 days who had contraindications to prophylactic anticoagulation were included. Screening duplex exams were obtained within 48 h of admission and then weekly. CT-angiography for PE was obtained if clinically indicated. Patients were excluded if they did not receive a duplex or if they had a post-injury VTE prior to ICU admission. Data regarding VTE rates (lower extremity [LE] DVT or PE), demographics, past medical history (PMH), injuries, and surgeries were collected. Univariate and multivariable analyses were performed to identify independent predictors of VTE with a p<0.05. RESULTS: 411 trauma patients with a mean age of 48 (SD 22) years and 8 (SD 9) ICU days were included. 72% were male and the mean ISS was 22 (SD 13). 30 (7.3%) patients developed VTE: 28 (6.8%) with LEDVT and 2 (0.5%) with PE. Risk factors for VTE with a p<0.2 on univariate analysis included: PMH of DVT, injury severity score (ISS), extremity fractures (Fx), and a pelvis or LE extremity Fx repair. After logistic regression, only PMH of DVT (OR=22.6) and any extremity Fx (OR=2.4) remained as independent predictors. CONCLUSION: VTE occur in 7% of critically injured trauma patients who cannot receive chemical prophylaxis. Aggressive screening and/or prophylactic IVCF placement may be considered in patients with a PMH of DVT or extremity fractures when anticoagulation is prohibited. PMID- 22047760 TI - Microscopy in 3D: a biologist's toolbox. AB - The power of fluorescence microscopy to study cellular structures and macromolecular complexes spans a wide range of size scales, from studies of cell behavior and function in physiological 3D environments to understanding the molecular architecture of organelles. At each length scale, the challenge in 3D imaging is to extract the most spatial and temporal resolution possible while limiting photodamage/bleaching to living cells. Several advances in 3D fluorescence microscopy now offer higher resolution, improved speed, and reduced photobleaching relative to traditional point-scanning microscopy methods. We discuss a few specific microscopy modalities that we believe will be particularly advantageous in imaging cells and subcellular structures in physiologically relevant 3D environments. PMID- 22047761 TI - Target separation of a new anti-tumor saponin and metabolic profiling of leaves of Panax notoginseng by liquid chromatography with eletrospray ionization quadrupole time-of-flight mass spectrometry. AB - A method coupling high-performance liquid chromatography (HPLC) with quadrupole time-of-flight mass spectrometers (QTOF-MS) using an eletrospray ionization (ESI) source was firstly developed for detection, characterization and guiding target separation of variants of protopanaxdiol saponin from leaves of Panax notoginseng. Under the guidance of LC-QTOF-MS, a new trace saponin was probed according to the precise elemental compositions of molecular ions and the fragmentation behavior, and then separated from the ethanol extract of the plant by a set of chromatographic methods. It was further confirmed by NMR experiments as 3-O-beta-D-glucopyranoside-3beta,l2beta,23beta-triol-20-ene-dammar (Pn-1). The cytotoxic assay showed that Pn-1 had relatively stronger anti-tumor effects against three tumor cell lines (NCI-H460, HepG2 and SGC-7901) than Rg3, an approved clinical agent for cancer therapy. Meanwhile, based on accurate mass measurements within 5 ppm for each molecular ions and subsequent product ions, 48 saponins, including 40 protopanaxadiol saponins, 7 protopanaxatriol saponins and 1 oleanane saponin were identified. It is noted that the knowledge of the presence of abundant protopanaxadiol saponins in leaves of P. notoginseng may provide tools for a full understanding of the chemical diversity of secondary metabolites from the different parts of P. notoginseng. From the points of time consuming and accurate mass measurement capability, the LC-QTOF-MS is a highly powerful tool for screening and guiding target separation of new compounds in herbal extract, and thus benefits the speed of new drug discovery progress. PMID- 22047763 TI - Resistance to avermectin/milbemycin anthelmintics in equine cyathostomins - current situation. AB - Avermectins and milbemycins (AM) are potent compounds against all major nematode parasites, but their continuous usage has led to the development of widespread resistance in many of the important species of ruminant and equine parasites. The exception to this has been the cyathostomins, where AM resistance was recently first reported only after decades of drug exposure. Data from a Brazilian study suggests that AM resistance has developed in cyathostomins and reports of shortened egg reappearance periods after ivermectin treatment have been published recently from USA and Germany. Thus, AM resistance in cyathostomins is an emerging worldwide concern, but there is only limited amount data on the extent of this problem. To limit the development and spread of AM-resistant cyathostomins the equine industry must implement new strategies for worm control, and the veterinary parasitology community must develop and validate improved protocols for detecting anthelmintic resistance in the field. PMID- 22047764 TI - Gotch ear: a poorly described, local, pathologic condition of livestock associated primarily with the Gulf Coast tick, Amblyomma maculatum. AB - Gotch ear is a condition in animals in which the ear is swollen, deformed, curled, drooped, possibly necrotic, and is usually associated with attachment by the Gulf Coast tick, Amblyomma maculatum. Little is known of the etiology or epidemiology of gotch ear in livestock. Reports generally describe the condition in cattle, but it has also been reported in horses and mules and more recently in a goat. This review explores the history and etymology of the term "gotch ear" and reports on current status, pathogenesis, differential diagnosis, and epidemiology of gotch ear. Finally, clinical definition of gotch ear is offered. PMID- 22047765 TI - Evidence that endogenous hydrogen sulfide exerts an excitatory effect on gastric motility in mice. AB - The present study was designed to investigate the effect of endogenous hydrogen sulfide (H2S) on gastric motility in mice. Western blotting and immunocytochemistry were used to determine expression levels of the H2S-producing enzymes cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) in gastric tissues and cultured smooth muscle cells. Physiological and intracellular recordings and the whole-cell patch clamp technique were used to evaluate the effect of H2S on the mechanical and electrical activities in muscle strips and in isolated smooth muscle cells, respectively. The results showed that CBS and CSE were expressed in mouse gastric smooth muscle. NaHS, a H2S donor, inhibited the amplitude and frequency of spontaneous contraction at high concentrations (>200 MUM). However, NaHS at low concentrations (<100 MUM) enhanced the basal tension and increased the contractile amplitude of muscle strips. This excitatory effect was not altered by the blockade of the enteric nerve with TTX, but was abolished by tetraethylammonium (TEA) or 4-aminopyridine (4-AP). Aminooxyacetic acid (AOA), but not propargylglycine (PAG), caused a concentration-dependent inhibition of spontaneous contraction. This effect was restored by L-cysteine and NaHS. In addition, NaHS at low concentrations (<100 MUM) produced a depolarization of the membrane potential, whereas AOA hyperpolarized the membrane potential and decreased the amplitude of slow waves. Furthermore, AOA increased whole-cell delayed rectifier K+ current (I(K(V))). These findings suggest that endogenous H2S appears to be an excitatory gaseous mediator during physiological regulation of gastric motility and this excitable effect is mediated by depolarization of the membrane potential via inhibition of I(K(V)). PMID- 22047762 TI - Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. AB - Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2-4, 2010, in Zurich, Switzerland, with the aim of reviewing current practice regarding liver transplantation in patients with HCC and to develop internationally accepted statements and guidelines. The format of the conference was based on the Danish model. 19 working groups of experts prepared evidence-based reviews according to the Oxford classification, and drafted recommendations answering 19 specific questions. An independent jury of nine members was appointed to review these submissions and make final recommendations, after debates with the experts and audience at the conference. This report presents the final 37 statements and recommendations, covering assessment of candidates for liver transplantation, criteria for listing in cirrhotic and non-cirrhotic patients, role of tumour downstaging, management of patients on the waiting list, role of living donation, and post-transplant management. PMID- 22047766 TI - Adsorption of humic acid onto carbonaceous surfaces: atomic force microscopy study. AB - The adsorption of humic acid (HA) onto highly ordered pyrolytic graphite (HOPG) surfaces at different concentrations has been studied by atomic force microscopy. When HA concentration was increased from 10 to 1,000 mg/L, HA can sequentially form spherical particles, layered structures, and connected blocks on HOPG surfaces. The findings of the layer structures and small amount of fine chains have been verified and discussed. When HA was acidified by addition of acetic acid, it changed into small rigid particles. These results indicated that HA can be considered as supramolecular associations of self-assembling heterogeneous and relatively small molecules, and a small amount of polymers. The present results are important for understanding HA molecular structures and their adsorption characteristic on carbonaceous surfaces. PMID- 22047767 TI - Successful management of a symptomatic splenic haemangioma by radiofrequency ablation. PMID- 22047768 TI - Effects of exposure to soluble fraction of industrial solid waste on lipid peroxidation and DNA methylation in erythrocytes of Oreochromis niloticus, as assessed by quantification of MDA and m5dC rates. AB - In this study, lipid peroxidation and DNA methylation were observed in erythrocytes of Oreochromis niloticus exposed to soluble fractions of textile, metal-mechanic and pulp and paper industrial waste, after a period of 48 h. Lipid peroxidation was quantified by the rate of malondialdehyde (MDA) and DNA methylation was quantified by the rate of 5-methyldeoxycytosine (m5dC). Soluble fractions of textile industrial waste caused metabolic changes for all studied samples. In organisms exposed to samples TX1 and TX2 (textile waste) MDA rates were 132.36 and 140.28 nM MDA/mg protein, respectively, while in control organism the MDA rates were 27.5 nM MDA/mg protein. All samples from soluble fractions of textile industrial waste induced increases in m5dC rates, increases varied between 300 percent and 700 percent when compared to the control organism. All the organisms exposed to soluble fractions of metal-mechanic industrial waste presented increases between 360 percent and 600 percent in the rates of MDA, and one of them (sample MM3) induced an increase of 180 percent in the rate of m5dC, when compared to control. Although a significant increase was not observed in the MDA rate of fish exposed to the soluble fractions of pulp and paper industrial waste, there was an increase of 460 percent in the rate of m5dC in one of the samples (sample PP2), when compared to control. The results showed that the soluble fractions of these industrial wastes are capable of inducing oxidative damage and altering the DNA methylation of O. niloticus. Thus, the MDA and m5dC rates demonstrated to be effective biomarkers of exposure, which could be used to evaluate the toxicity of soluble fractions of industrial solid waste. PMID- 22047769 TI - Assessment of the genotoxicity of quinolone and fluoroquinolones contaminated soil with the Vicia faba micronucleus test. AB - The genotoxicity of quinolone and fluroquinolones was assessed using the micronucleus (MN) test on Vicia faba roots by direct contact exposure to a solid matrix. Plants were exposed to quinolones (nalidixic acid) and fluoroquinolones (ciprofloxacin and enrofloxacin) alone or mixed with artificially contaminated soils. Four different concentrations of each of these antibiotics were tested (0.01, 0.1, 1 and 10 mg/Kg) for nalidixic acid and (0.005, 0.05, 0.5 and 5 mg/Kg) for ciprofloxacin and enrofloxacin. These antibiotics were also used in mixture. Exposure of Vicia faba plants to each antibiotic at the highest two concentrations showed significant MN induction. The lowest two concentrations had no significant genotoxic effect. The mixture of the three compounds induced a significant MN induction whatever the mixture tested, from 0.02 to 20 mg/Kg. The results indicated that a similar genotoxic effect was obtained with the mixture at 0.2 mg/Kg in comparison with each molecule alone at 5-10 mg/Kg. Data revealed a clear synergism of these molecules on Vicia faba genotoxicity. PMID- 22047770 TI - A phase II study of gemcitabine in combination with tanespimycin in advanced epithelial ovarian and primary peritoneal carcinoma. AB - OBJECTIVE: To evaluate the efficacy and biological effects of the gemcitabine/tanespimycin combination in patients with advanced ovarian and peritoneal cancer. To assess the effect of tanespimycin on tumor cells, levels of the chaperone proteins HSP90 and HSP70 were examined in peripheral blood mononuclear cells (PBMC) and paired tumor biopsy lysates. METHODS: Two-cohort phase II clinical trial. Patients were grouped according to prior gemcitabine therapy. All participants received tanespimycin 154 mg/m(2) on days 1 and 9 of cycle 1 and days 2 and 9 of subsequent cycles. Patients also received gemcitabine 750 mg/m(2) on day 8 of the first treatment cycle and days 1 and 8 of subsequent cycles. RESULTS: The tanespimycin/gemcitabine combination induced a partial response in 1 gemcitabine naive patient and no partial responses in gemcitabine resistant patients. Stable disease was seen in 6 patients (2 gemcitabine naive and 4 gemcitabine resistant). The most common toxicities were hematologic (anemia and neutropenia) as well as nausea and vomiting. Immunoblotting demonstrated limited upregulation of HSP70 but little or no change in levels of most client proteins in PBMC and paired tumor samples. CONCLUSIONS: Although well tolerated, the tanespimycin/gemcitabine combination exhibited limited anticancer activity in patients with advanced epithelial ovarian and primary peritoneal carcinoma, perhaps because of failure to significantly downregulate the client proteins at clinically achievable exposures. PMID- 22047771 TI - [An atypical case of asthma]. PMID- 22047772 TI - Patterns of health services utilization in rural Canada. AB - CONTEXT OF THIS STUDY: Canadians value ease of access to their health services. Although many studies have focused on accessibility to health services in Canada, few have examined rural-urban differences in this aspect, particularly from a national perspective. Yet disparities in access to health services exist between rural and urban populations, as do the challenges of delivering health care to more remote areas or to those with small populations. "Canada's Rural Communities: Understanding Rural Health and Its Determinants" is a three-year research project co-funded by the Canadian Population Health Initiative (CPHI) of the Canadian Institute for Health Information (CIHI) and the Public Health Agency of Canada (PHAC). It involves investigators from the Public Health Agency of Canada, the Centre for Rural and Northern Health Research (CRaNHR) at Laurentian University, and other researchers. The first publication of the research project was How Healthy Are Rural Canadians? An Assessment of Their Health Status and Health Determinants; this, the second publication, is a descriptive analysis of the utilization patterns of a broad range of health services by rural residents compared to their urban counterparts. PMID- 22047774 TI - Altered postural control in persons with cognitive impairment during visual feedback tasks. AB - We compared postural stability with eyes open (EO) and with visual feedback (VFB) in 15 elderly subjects with cognitive impairment (SwCI) and 17 controls. Postural stability was evaluated using the center-of-pressure (COP) mean radius and velocity, while postural strategies by the frequency and damping of the difference between the COP and the center-of-mass (COM) signals. Performance in the VFB trials was measured by the ratio of time spent by the COP inside the target on the screen to the total trial duration. With EO, both groups demonstrated similar postural stability and strategies. The time spent inside the target during VFB was significantly higher in controls than in SwCI. The VFB did not affect the mean radius in either group, nor velocity and frequency in SwCI, however it increased the mean velocity and frequency in controls. Besides, the VFB increased damping significantly more in the SwCI than in controls. These findings indicate that controls adequately responded to the demands of VFB and used efficient strategy of postural control. In contrast, the SwCI seemed to have lost the natural capability to use augmented feedback demonstrating impaired sway control and deficit of sensory integration. All these symptoms of posture control disorders could be objectively identified by the COP mean velocity and the COP COM frequency and damping. Increased damping in controls during VFB task may account for early signs of cognitive impairment that cannot be captured by standard tests. PMID- 22047773 TI - One walk a year to 1000 within a year: continuous in-home unobtrusive gait assessment of older adults. AB - Physical performance measures predict health and function in older populations. Walking speed in particular has consistently predicted morbidity and mortality. However, single brief walking measures may not reflect a person's typical ability. Using a system that unobtrusively and continuously measures walking activity in a person's home we examined walking speed metrics and their relation to function. In 76 persons living independently (mean age, 86) we measured every instance of walking past a line of passive infra-red motion sensors placed strategically in their home during a four-week period surrounding their annual clinical evaluation. Walking speeds and the variance in these measures were calculated and compared to conventional measures of gait, motor function and cognition. Median number of walks per day was 18+/-15. Overall mean walking speed was 61+/-17 cm/s. Characteristic fast walking speed was 96 cm/s. Men walked as frequently and fast as women. Those using a walking aid walked significantly slower and with greater variability. Morning speeds were significantly faster than afternoon/evening speeds. In-home walking speeds were significantly associated with several neuropsychological tests as well as tests of motor performance. Unobtrusive home walking assessments are ecologically valid measures of walking function. They provide previously unattainable metrics (periodicity, variability, range of minimum and maximum speeds) of everyday motor function. PMID- 22047775 TI - An optimized Kalman filter for the estimate of trunk orientation from inertial sensors data during treadmill walking. AB - The aim of this study was the fine tuning of a Kalman filter with the intent to provide optimal estimates of lower trunk orientation in the frontal and sagittal planes during treadmill walking at different speeds using measured linear acceleration and angular velocity components represented in a local system of reference. Data were simultaneously collected using both an inertial measurement unit (IMU) and a stereophotogrammetric system from three healthy subjects walking on a treadmill at natural, slow and fast speeds. These data were used to estimate the parameters of the Kalman filter that minimized the difference between the trunk orientations provided by the filter and those obtained through stereophotogrammetry. The optimized parameters were then used to process the data collected from a further 15 healthy subjects of both genders and different anthropometry performing the same walking tasks with the aim of determining the robustness of the filter set up. The filter proved to be very robust. The root mean square values of the differences between the angles estimated through the IMU and through stereophotogrammetry were lower than 1.0 degrees and the correlation coefficients between the corresponding curves were greater than 0.91. The proposed filter design can be used to reliably estimate trunk lateral and frontal bending during walking from inertial sensor data. Further studies are needed to determine the filter parameters that are most suitable for other motor tasks. PMID- 22047776 TI - Predictors of pelvic retraction in children with cerebral palsy derived from gait parameters and clinical testing. AB - Excessive pelvic rotation in the transverse plane is common in patients with cerebral palsy. Knowing the underlying reasons is important for clinical decision making, since changes in pelvic retraction might have an effect on internally rotated gait. We hypothesized that the contralateral leg contributes considerably to pelvic rotation on the retracted side. Therefore the aim of this study is to calculate predictors for pelvic retraction using both, parameters from the retracted and from the contralateral protracted side. Thirty-two children with diplegia and 18 children with hemiplegia were examined by three-dimensional gait analysis followed by a clinical examination protocol. Stepwise multilinear regression of the response value mean pelvic retraction during stance phase was performed on 10 potential predictors of dynamic gait data and 10 corresponding predictors of clinical data of the retracted and the contralateral protracted side. Gait analysis revealed ankle push-off energy on the protracted side as the best predictors in hemiplegic patients explaining 59% of the variance in pelvic retraction. In diplegic patients external hip rotation of the protracted side was most accurate in predicting pelvic retraction (27%). Best clinical predictors for hemiplegic patients were ankle dorsiflexion on the retracted side (46%) and for diplegic patients it was the knee extension strength on the protracted side together with hip rotation on the retracted side (36%). In hemiplegic patients ankle push-off energy of the contralateral side is a significant compensation mechanism that might cause increased pelvic retraction to compensate for the weakness of the involved side. In diplegic patients prediction of pelvic retraction was only moderate and requires further investigation. PMID- 22047778 TI - Predictive coding as a model of the V1 saliency map hypothesis. AB - The predictive coding/biased competition (PC/BC) model is a specific implementation of the predictive coding theory that has previously been shown to provide a detailed account of the response properties of orientation tuned cells in primary visual cortex (V1). Here it is shown that the same model can successfully simulate psychophysical data relating to the saliency of unique items in search arrays, of contours embedded in random texture, and of borders between textured regions. This model thus provides a possible implementation of the hypothesis that V1 generates a bottom-up saliency map. However, PC/BC is very different from previous models of visual salience, in that it proposes that saliency results from the failure of an internal model of simple elementary image components to accurately predict the visual input. Saliency can therefore be interpreted as a mechanism by which prediction errors attract attention in an attempt to improve the accuracy of the brain's internal representation of the world. PMID- 22047779 TI - Empowerment in family planning as viewed by Iranian women: a qualitative study. AB - Women carry the primary responsibility for family planning in most parts of the world, and should be afforded the power of decision-making and control over their fertility. This study seeks to gain insight into Iranian women's perception of the meaning of empowerment in family planning. Using a qualitative study, seven focus group discussions and five individual interviews were conducted with 35 married Iranian women of reproductive age. The data were analysed using a conventional content analysis approach, in which themes and categories were explored to reveal women's experiences of empowerment in family planning. The results demonstrated four main categories: control over fertility plan, participative family planning, maintaining health and access to optimal family planning services. They viewed knowledge of family planning and autonomy of decision-making in fertility issues as essential elements for control of their fertility plan. Participants felt more empowered when joint family planning decisions were made with their partners in an atmosphere of agreement. Therefore, family planning policymakers should plan services with new approaches that focus on women's health and empowerment. PMID- 22047777 TI - Testosterone impairs the acquisition of an operant delayed alternation task in male rats. AB - The current study examined the effects of gonadectomy (GDX) and subsequent testosterone treatment of male Long-Evans rats on an operant variable delay spatial alternation task (DSA). Gonadally-intact rats (intact-B), GDX rats receiving implants that delivered a physiological level of testosterone (GDX-T), and GDX rats receiving blank implants (GDX-B) were tested for 25 sessions on a DSA task with variable inter-trial delays ranging from 0 to 18 s. Acquisition of the DSA task was found to be enhanced following GDX in a time and delay dependent manner. Both the GDX-T and the intact-B rats had lower performance accuracies across delays initially, relative to GDX-B rats, and this deficit persisted into subsequent testing sessions at longer delays. The GDX-T and intact-B rats also had a tendency to commit more perseverative errors during the early testing sessions, with both groups persisting in pressing a lever which had not been associated with reinforcement for at least two consecutive trials. However, both the GDX-T and intact-B groups were able to achieve performance accuracy similar to that of the GDX-B rats by the final sessions of testing. Overall, these results suggest that castration of adult male rats enhances their acquisition of an operant DSA task. PMID- 22047780 TI - Obituary: Dr Max Harry Weil. PMID- 22047781 TI - Anticoagulation management in clinical practice: preventing stroke in patients with atrial fibrillation. AB - Atrial fibrillation (AF) is a major and widely recognized risk factor for cardioembolic stroke. Prophylactic therapy for the prevention of stroke in patients with AF is often achieved through oral anticoagulation, specifically with warfarin, which has been used for this purpose for more than 50 years. Although warfarin therapy is effective when implemented appropriately, it is often underutilized and requires consistent monitoring to ensure both safety in avoiding bleeding and efficacy in preventing strokes. Because the burden of AF related stroke continues to rise, healthcare professionals need to understand the strengths and limitations of current and emerging treatment options. This review outlines current practices for managing the risk of stroke with anticoagulation in patients with AF, and discusses how new oral anticoagulants may affect clinical practice. PMID- 22047782 TI - Characterizing upper limb muscle volume and strength in older adults: a comparison with young adults. AB - Aging is associated with the loss of muscle volume (MV) and force leading to difficulties with activities of daily living. However, the relationship between upper limb MV and joint strength has not been characterized for older adults. Quantifying this relationship may help our understanding of the functional declines of the upper limb that older adults experience. Our objective was to assess the relationship between upper limb MV and maximal isometric joint moment generating capacity (IJM) in a single cohort of healthy older adults (age >= 65 years) for 6 major functional groups (32 muscles). MV was determined from MRI for 18 participants (75.1+/-4.3 years). IJM at the shoulder (abduction/adduction), elbow (flexion/extension), and wrist (flexion/extension) was measured. MV and IJM measurements were compared to previous reports for young adults (28.6+/-4.5 years). On average older adults had 16.5% less total upper limb MV compared to young adults. Additionally, older adult wrist extensors composed a significantly increased percentage of upper limb MV. Older adult IJM was reduced across all joints, with significant differences for shoulder abductors (p<0.0001), adductors (p=0.01), and wrist flexors (p<0.0001). Young adults were strongest at the shoulder, which was not the case for older adults. In older adults, 40.6% of the variation in IJM was accounted for by MV changes (p<=0.027), compared to 81.0% in young adults. We conclude that for older adults, MV and IJM are, on average, reduced but the significant linear relationship between MV and IJM is maintained. These results suggest that older adult MV and IJM cannot be simply scaled from young adults. PMID- 22047783 TI - The early migration of a partially cemented fluted pegged glenoid component using radiostereometric analysis. AB - BACKGROUND: Radiostereometric analysis measures the position of rigid bodies in 3 dimensions with very high precision and can be used to measure early micromotion of glenoid implants. MATERIALS AND METHODS: Radiostereometric analysis was used to measure migration of 11 partially cemented fluted pegged glenoid components in patients with osteoarthritis who underwent shoulder arthroplasty during a 2-year period. Patients were evaluated using the American Shoulder and Elbow Surgeons (ASES) and Constant scores and by a computed tomography (CT) scan at the 2-year follow-up. RESULTS: Migration patterns could be classified into 2 groups: The first group showed little if any migration, the second group rotated by 4 degrees or more as early as 3 months after operation. The maximum total point motion reached up to 2 mm by the 6-month follow-up. At 12 months, the 2 groups could be identified by the presence or absence of focal lucency around the central peg. At the end of 2 years, CT scans were able to classify the same 2 migration patterns by the presence or absence of osseointegration around the cementless central peg of the glenoid implant. The clinical effect of the absence of osseointegration in this novel glenoid component is unknown because both groups had similar clinical results at 2 years. CONCLUSION: Rapid early migration associated with focal lucency and absence of osseointegration was observed in 6 of 11 components. We postulate that lack of initial fixation leads to early movement of the glenoid component and failure of osseointegration. PMID- 22047784 TI - Glenohumeral joint tuberculosis that mimics frozen shoulder: a retrospective analysis. AB - BACKGROUND: Although the incidence of osteoarticular tuberculosis is increasing, glenohumeral joint tuberculosis is rare and often misdiagnosed in its early stages. Our objective was to study the incidence of the initial misdiagnosis as frozen shoulder and the duration of the prediagnostic period among patients with glenohumeral joint tuberculosis. METHODS: The clinical records of 21 patients with tuberculosis of the shoulder joint were retrospectively analyzed. RESULTS: Among the 16 patients with glenohumeral joint tuberculosis, 14 (87.5%) were initially diagnosed as having frozen shoulder instead of glenohumeral joint tuberculosis at their primary care clinics. Two patients actually showed both shoulder pain and limited range of motion, although they did not have a record of initial diagnosis with frozen shoulder. Consequently, 14 (87.5%) of the patients in our study with glenohumeral joint tuberculosis were likely misdiagnosed as having frozen shoulder. On the other hand, this group accounted for 3.6% (n = 16) of 450 patients who, during the same period, had been initially diagnosed with frozen shoulder at our institution. The mean prediagnostic period to attain the final, correct diagnosis of glenohumeral joint tuberculosis for this group was 14.5 months. CONCLUSION: It appears that misdiagnosis is common and early diagnosis of tubercular infection in the glenohumeral joint has become increasingly difficult. Glenohumeral joint tuberculosis should be suspected in cases of longstanding pain in the shoulder. It is necessary to re-examine these frozen shoulder patients with repeated plain radiographs followed by further imaging studies, especially magnetic resonance imaging, if conservative therapy fails. PMID- 22047785 TI - Defining functional shoulder range of motion for activities of daily living. AB - INTRODUCTION: The range of motion (ROM) in the wrist and elbow required for daily activities has been reported to be less than the normal anatomic ROM. This functional ROM has not been defined for the shoulder. Many shoulder outcome assessment tools use specific functional tasks of daily living to score functional results of treatment. This study quantified the total shoulder ROM required to perform the functional tasks of the American Shoulder and Elbow Surgeon (ASES), Simple Shoulder Test (SST), and University of Pennsylvania (U Penn) Shoulder Score (PSS). MATERIALS AND METHODS: The FASTRAK electromagnetic tracking system (Colchester, VT, USA) was used to test 40 shoulders in 20 volunteers with no shoulder pathology found on physical examination. Three sensors were used: 1 each on the T3 spinous process, the scapular spine, and the arm over the distal humerus. Subjects performed each functional task of the ASES, SST, and PSS while flexion, extension, abduction, adduction, external rotation, and internal rotation were recorded. RESULTS: Average shoulder motions required to perform the 10 functional tasks were flexion, 121 degrees +/- 6.7 degrees ; extension, 46 degrees +/- 5.3 degrees ; abduction, 128 degrees +/- 7.9 degrees ; cross-body adduction, 116 degrees +/- 9.1 degrees ; external rotation with the arm 90 degrees abducted, 59 degrees +/- 10 degrees ; and internal rotation with the arm at the side, 102 degrees +/- 7.7 degrees . CONCLUSION: Although attaining full motion is a reasonable goal of all shoulder treatment, our results indicate that less ROM is required to perform the functional tasks used in common outcome tools. PMID- 22047786 TI - The importance of inferomedial support in the hot air balloon technique for treatment of 3-part proximal humeral fractures. AB - HYPOTHESIS: Inferomedial support may affect the results of the hot air balloon technique for the treatment of displaced, 3-part fractures of the proximal humerus. METHODS: Forty-three patients with displaced, 3-part fractures of the proximal humerus treated with the hot air balloon technique between 1995 and 2007 were included in the study. All patients were classified into 4 subgroups based on the presence or absence of medial buttress restoration and inferomedial screw insertion (R+, restored with inferomedial screw; R-, restored without inferomedial screw; NR+, non-restored with inferomedial screw; and NR-, non restored without inferomedial screw). Assessment of radiologic and clinical outcome among subgroups was based on evaluation of neck-shaft angle, American Shoulder and Elbow Surgeons score, and Neer score. RESULTS: The mean follow-up duration was 65 +/- 29.7 months. The change in the neck-shaft angle in the R+, R , NR+, and NR- groups was 3 degrees , 2 degrees , 3 degrees , and 11 degrees , respectively. The mean American Shoulder and Elbow Surgeons scores in the R+, R-, NR+, and NR- groups were 91 +/- 4.8, 86 +/- 5.4, 85 +/- 1.9, and 77 +/- 5.8, respectively. The mean Neer scores in the R+, R-, NR+, and NR- groups were 92 +/- 4.3, 88 +/- 4.0, 87 +/- 2.1, and 76 +/- 8.2, respectively. CONCLUSIONS: Medial buttress restoration and inferomedial screw insertion affect bone-nail construct stability and clinical outcomes. PMID- 22047787 TI - Glenoid loosening and failure in anatomical total shoulder arthroplasty: is revision with a reverse shoulder arthroplasty a reliable option? AB - INTRODUCTION: Our purpose was to evaluate if, in case of aseptic glenoid loosening and failure in anatomical total shoulder arthroplasty (TSA), revision by a reverse shoulder arthroplasty (RSA) is a reliable therapeutic option. METHODS: Retrospective multicenter cohort study of 37 consecutive anatomical TSA revised by RSA for aseptic glenoid loosening or failure. The decision to implant a RSA was related to the presence of associated complications: rotator cuff tears (n = 24), subscapularis insufficiency (n = 29), prosthetic instability (n = 13), and glenoid bone deficiency (n = 37). The patients were reviewed clinically and radiographically at a mean follow-up of 47 months (range, 24-104). RESULTS: Eighty-six percent of the patients were satisfied or very satisfied. The average Constant score increased from 24 to 55 pts (P < .0001) and active anterior elevation from 68 degrees to 121 degrees (P < .0001). Twenty-two of the 29 (76%) associated bone grafts were incorporated in the glenoid. Eight patients (21%) needed a subsequent reoperation because of recurrent or new complications: glenoid loosening (n = 3), prosthetic anterior instability (n = 3), and humeral subsidence (n = 2); the reverse prosthesis had to be converted to a hemiarthroplasty in 1 patient and removed in another. CONCLUSION: Revision with a RSA is a reliable therapeutic option which provides the double benefit of glenoid bone stock reconstruction by fixing the bone graft with the help of the baseplate and screws and of solving the problem of soft tissue insufficiency and prosthetic instability. However, surgeons should be aware that the rate of postoperative complications and subsequent reoperations is high, and that the surgical technique is demanding. PMID- 22047788 TI - A biomechanical analysis of gap formation and failure mechanics of a xenograft reinforced rotator cuff repair in a cadaveric model. AB - HYPOTHESIS: Failure rates of rotator cuff repairs are reported to be as high as 90%, in part because of gap formation at the repair site that occurs before healing. The purpose of this study was to evaluate whether the application of an extracellular matrix (ECM) graft (Conexa; Tornier, Edina, MN, USA) to a rotator cuff repair will decrease the gap formation at the tendon-bone interface and increase the ultimate load to failure over control specimens by mechanically sharing load with the repair in a cadaveric model. METHODS: Six pairs of human cadaveric shoulders were used to test ECM-reinforced and unreinforced rotator cuff repairs for repair-site gapping, ultimate load, failure mode, and load sharing capabilities of the ECM patch under both cyclic and monotonic loading. RESULTS: The gap formation under cyclic loading was reduced by 40% for the reinforced specimens compared with the control group (1.3 +/- 0.6 mm vs 2.1 +/- 0.5 mm, P < .05) The load at 5-mm gap formation was significantly higher for the reinforced group (389 +/- 71 N) compared with the control group (307 +/- 33 N) (P < .05). The ultimate load to failure was significantly higher for the ECM reinforced group compared with the control group: 429 +/- 69 N versus 335 +/- 57 N (P < .05). The ECM graft was estimated to share 35% of the load applied to the tendon repair. CONCLUSIONS: Application of an ECM graft to a rotator cuff repair decreased tendon gapping and increased load to failure by load sharing in a human rotator cuff repair model. PMID- 22047789 TI - Early clinical and structural results after autologous chondrocyte transplantation at the glenohumeral joint. AB - BACKGROUND: The purpose of the study was to report early functional and radiographic results of a small series of patients who underwent autologous chondrocyte transplantation-collagen membrane seeding (ACT-Cs) for focal chondral defects of the shoulder. METHODS: The outcome of 4 consecutive male patients (mean age, 29.3 +/- 6.2 years; range, 21-36 years) who underwent ACT-Cs for treatment of large symptomatic glenohumeral cartilage defects was retrospectively evaluated with clinical and radiographic measures at a mean of 41.3 +/- 24.9 months (range, 11-71 months) after surgery. The evaluation included a visual analog scale for pain, the Constant score, the American Shoulder and Elbow Surgeons shoulder index, the Rowe score, and a satisfaction scale. Magnetic resonance imaging evaluation was performed according to the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. RESULTS: There were 3 humeral full-thickness cartilage defects (each 6.0 cm(2)) and 1 glenoid full thickness cartilage defect (2.0 cm(2)). The mean postoperative visual analog scale score (0.3 of 10), the mean unweighted Constant score (83.3 +/- 9.9), and the mean American Shoulder and Elbow Surgeons index (95.3 +/- 8.1) were representative of satisfactory shoulder function. The Magnetic Resonance Observation of Cartilage Repair Tissue score was indicative of satisfactory defect coverage with signs of fibrocartilaginous repair tissue. CONCLUSIONS: Autologous chondrocyte transplantation at the glenohumeral joint is a remote option for young adults with symptomatic, isolated, large-diameter cartilage lesions. Potential complications as a result of the open approach and 2-step procedure have to be considered carefully. Long-term data, larger patient populations, and randomized studies are required to determine the potential for chondrocyte transplantation techniques to be standard procedure for treatment of symptomatic, large-diameter, full-thickness cartilage defects in the glenohumeral joint. PMID- 22047790 TI - Drug-related arrest rates and spatial access to syringe exchange programs in New York City health districts: combined effects on the risk of injection-related infections among injectors. AB - Drug-related law enforcement activities may undermine the protective effects of syringe exchange programs (SEPs) on local injectors' risk of injection-related infections. We explored the spatial overlap of drug-related arrest rates and access to SEPs over time (1995-2006) in New York City health districts, and used multilevel models to investigate the relationship of these two district-level exposures to the odds of injecting with an unsterile syringe. Districts with better SEP access had higher arrest rates, and arrest rates undermined SEPs' protective relationship with unsterile injecting. Drug-related enforcement strategies targeting drug users should be de-emphasized in areas surrounding SEPs. PMID- 22047791 TI - Phosphodiesterase function and endocrine cells: links to human disease and roles in tumor development and treatment. AB - Phosphodiesterases (PDEs) are enzymes that regulate the intracellular levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate, and, consequently, exhibit a central role in multiple cellular functions. The pharmacological exploitation of the ability of PDEs to regulate specific pathways has led to the discovery of drugs with selective action against specific PDE isoforms. Considerable attention has been given to the development of selective PDE inhibitors, especially after the therapeutic success of PDE5 inhibitors in the treatment of erectile dysfunction. Several associations between PDE genes and genetic diseases have been described, and more recently PDE11A and PDE8B have been implicated in predisposition to tumor formation. This review focuses on the possible function of PDEs in a variety of tumors, primarily in endocrine glands, both in tumor predisposition and as potential therapeutic targets. PMID- 22047792 TI - Regulation of murine cardiac function by phosphodiesterases type 3 and 4. AB - Cyclic nucleotide phosphodiesterases (PDEs) encompass a large group of enzymes that regulate intracellular levels of two-second messengers, cAMP and cGMP, by controlling the rates of their degradation. More than 60 isoforms, subdivided into 11 gene families (PDE1-11), exist in mammals with at least six families (PDE1-5 and PDE8) identified in mammalian hearts. The two predominant families implicated in regulating contraction strength of the heart are PDE3 and PDE4. Studies using transgenic models in combination with family-specific PDE inhibitors have demonstrated that PDE3A, PDE4B, and PDE4D isoforms regulate cardiac contractility by modulating cAMP levels in various subcellular compartments. These studies have further uncovered contributions of PDE4B and PDE4D in preventing ventricular arrhythmias. PMID- 22047794 TI - [Epidemiological study of the metabolic diseases with homocystinuria in Spain]. AB - OBJECTIVES: To determine the prevalence of homocystinuria in Spain and to establish the measures and mechanisms to ensure its prevention, diagnosis and treatment. MATERIAL AND METHODS: A national cross-sectional survey was conducted by means of a questionnaire sent to 35 hospitals in which children and adult patients are treated. RESULTS: Using the questionnaires submitted by 25 physicians from 16 centres, 75 patients were identified: 41 transsulphuration defects (one deceased), 27 remethylation (six deaths) and 7 without a syndromic diagnosis. The age at diagnosis varied widely, and 18 cases had more than one sibling affected. The more severe clinical manifestations involved the patients with remethylation defects. There was a high percentage of cognitive impairment, followed by lens diseases. Almost half of the patients had neurological disorders. There was increased vascular involvement in CBS-deficient adults. The therapeutic options most used were, folic acid, hydroxycobalamin and betaine. CONCLUSIONS: In view of these results and especially the small number of CBS deficiencies detected, we conclude that there is a need to introduce newborn screening for classical homocystinuria and ensure implementation of an appropriate diagnostic workup in all patients at risk. PMID- 22047793 TI - Adolescent treatment initiation and engagement in an evidence-based practice initiative. AB - This study examined client and program factors predicting initiation and engagement for 2,191 adolescents at 28 outpatient substance abuse treatment sites implementing evidence-based treatments. Using Washington Circle criteria for treatment initiation and engagement, 76% of the sample initiated, with 59% engaging in treatment. Analyses used a 2-stage Heckman probit regression, accounting for within-site clustering, to identify factors predictive of initiation and engagement. Adolescents treated in a pay-for-performance (P4P) group were more likely to initiate, whereas adolescents in the race/ethnicity category labeled other (Native American, Asian, Pacific Islander, Native Alaskan, Native Hawaiian, mixed race/ethnicity), or who reported high truancy, were less likely to initiate. Race/ethnicity groups other than Latinos were equally likely to engage. Among White adolescents, each additional day from first treatment to next treatment reduced likelihood of engagement. Although relatively high initiation and engagement rates were achieved, the results suggest that attention to program and client factors may further improve compliance with these performance indicators. PMID- 22047795 TI - Special issue on techniques for measuring brain connectivity: advanced anatomic, function, effective and network neuroconnectivity techniques. PMID- 22047796 TI - Effects of water temperature increase and heavy metals contamination on WAP65 gene expression in sea bass (Dicentrarchus labrax) liver. AB - It has been previously demonstrated that "Warm temperature Acclimation-related 65 kD Protein" (WAP65) is involved in temperature acclimation, response to intoxication and infection, as well as in development. The expression of wap65-1 was investigated in the liver of European sea bass (Dicentrarchus labrax) during exposure to the increased temperature (from 12 deg C to 30 deg C) and during intoxication with four heavy metals: lead, cadmium, copper and zinc. Post temperature increase wap65 expression was highest after one hour at 30 deg C. After 1 to 4 weeks at 30 deg C wap65 transcript levels did not differ from the 12 deg C control group, similar to observations regarding the heat shock protein, hsp70. Upregulation of wap65 was detected after treatment (intoxication) with cadmium (0.5 MUg/l). In contrast, a slight, but significant down regulation of wap65 was seen after copper (5 MUg/l) intoxication. These data indicate that functional analyses of WAP65 are needed to understand the differential regulation of this gene by metals. The role of WAP65 may be similar to that of HSP70, which has generalized functions in responding to certain stressors and maintaining normal cell physiology. PMID- 22047797 TI - Effect of 2',6'-dimethyl-L-tyrosine (Dmt) on pharmacological activity of cyclic endomorphin-2 and morphiceptin analogs. AB - This study reports the synthesis and biological evaluation of a series of new side-chain-to-side-chain cyclized endomorphin-2 (EM-2) and morphiceptin analogs of a general structure Tyr-c(Xaa-Phe-Phe-Yaa)NH(2) or Tyr-c(Xaa-Phe-D-Pro Yaa)NH(2), respectively, where Xaa and Yaa were L/D Asp or L/D Lys. Further modification of these analogs was achieved by introduction of 2',6'-dimethyl-L tyrosine (Dmt) instead of Tyr in position 1. Peptides were synthesized by solid phase method and cleaved from the resin by a microwave-assisted procedure. Dmt(1) substituted analogs displayed high affinity at the MU-opioid receptors, remained intact after incubation with the rat brain homogenate and showed remarkable, long lasting MU-opioid receptor-mediated antinociceptive activity after central, but not peripheral administration. Our results demonstrate that cyclization is a promising strategy in the development of new opioid analgesics, but further modifications are necessary to enhance the blood-brain barrier permeability. PMID- 22047798 TI - B-Ring-modified and/or 5-demethylated nobiletin congeners: inhibitory activity against pro-MMP-9 production. AB - Three metabolites and 12 analogues of nobiletin (1) were synthesized. Whereas nobiletin derivatives 2-4 inhibited pro-MMP-9 production similarly in both PMA- and TNF-alpha-stimulated human lens epithelial cells, the 2'-hydroxylated analogue 5a exerted marked inhibitory effects (IC(50): 0.4 MUM) on PMA-treated cells, which were 170-fold more potent than those on TNF-alpha-treated cells. This activity may be closely related to PKC-mediated transcriptional regulation of pro-MMP-9. PMID- 22047799 TI - Quinoline tricyclic derivatives. Design, synthesis and evaluation of the antiviral activity of three new classes of RNA-dependent RNA polymerase inhibitors. AB - In this study three new classes of linear N-tricyclic compounds, derived by condensation of the quinoline nucleus with 1,2,3-triazole, imidazole or pyrazine, were synthesized, obtaining triazolo[4,5-g]quinolines, imidazo[4,5-g]quinolines and pyrido[2,3-g]quinoxalines, respectively. Title compounds were tested in cell based assays for cytotoxicity and antiviral activity against RNA viruses representative of the three genera of the Flaviviridae family, that is BVDV (Pestivirus), YFV (Flavivirus) and HCV (Hepacivirus). Quinoline derivatives were also tested against representatives of other RNA virus families containing single stranded, either positive-sense (ssRNA(+)) or negative-sense (RNA(-)), and double stranded genomes (dsRNA), as well as against representatives of two DNA virus families. Some quinolines showed moderate, although selective activity against CVB-5, Reo-1 and RSV. However, derivatives belonging to all classes showed activity against BVDV. Among the most potent were the bis-triazoloquinoline 1m, the imidazoquinolines 2e and 2h, and the pyridoquinoxalines 4h, 4j and 5n (EC(50) range 1-5 MUM). When tested in a replicon assay, compound 2h was the sole derivative to also display anti-HCV activity (EC(50)=3.1 MUM). In enzyme assays, 1m, 2h, 5m and 5n proved to be potent inhibitors of the BVDV RNA-dependent RNA polymerase (RdRp), while only 2h also inhibited the recombinant HCV enzyme. PMID- 22047800 TI - Benzenepolycarboxylic acids with potential anti-hemorrhagic properties and structure-activity relationships. AB - Previously, we reported the structural requirements of the cinnamic acid relatives for inhibition of snake venom hemorrhagic action. In the present study, we examined the effect of benzenepolycarboxylic acids and substituted benzoic acids against Protobothropsflavoviridis venom-induced hemorrhage. Pyromellitic acid (1,2,4,5-benzenetetracarboxylic acid) was found to be a potent inhibitor of hemorrhage, with an IC(50) value of 0.035 MUM. In addition, most of the antihemorrhagic activity of compounds tested in this experiment showed good correlation to acidity. PMID- 22047801 TI - 2-Anilinonicotinyl linked 2-aminobenzothiazoles and [1,2,4]triazolo[1,5-b] [1,2,4]benzothiadiazine conjugates as potential mitochondrial apoptotic inducers. AB - A series of N-(2-anilino-pyridyl) linked 2-amino benzothiazoles (4a-n) and [1,2,4]triazolo [1,5-b]benzothiadiazine conjugates (5a-j) have been designed, synthesized and evaluated for their antiproliferative activity. Some of these compounds (4h-k, 4n, and 5e) have exhibited potent cytotoxicity specifically against human leukemia HL-60 cell lines with IC(50) values in the range of 0.08 0.70 MUM. All these compounds were tested for their effects on the cell cycle perturbations and induction of apoptosis. Morphological evidences of apoptosis, including fragmentation of nuclei and inter nucleosomal DNA laddering formation were clearly observed after 24h exposure to compound 4i. Flow cytometry analysis revealed that compound 4i showed drastic cell cycle perturbations due to concentration dependant increase in the sub-G0 region which comprises of both the apoptotic and debris fraction, thus implying the extent of cell death. These compounds trigger the mitochondrial apoptotic pathway that results in the loss of mitochondrial membrane potential through activation of multiple caspases followed by activation of caspase-3, and finally cleavage of PARP. Further the mechanism of cell death was analysed by fluorescent microscopic analysis and also by scanning electron microscopy. The cytotoxicity of 4i correlated with induction of apoptosis, caspases activation and DNA damage and thus indicating the apoptotic pathway of anticancer effect of these compounds. PMID- 22047802 TI - The arginine mimicking beta-amino acid beta3hPhe(3-H2N-CH2) as S1 ligand in cyclotheonamide-based beta-tryptase inhibitors. AB - beta-Tryptase, a mast-cell specific serine protease with trypsin-like activity, has emerged in the last years as a promising novel therapeutic target in the field of allergic inflammation. Recently, we have developed a potent and selective beta-tryptase inhibitor based on the natural product cyclotheonamide E4 by implementing a basic P3 residue that addresses the determinants of the extended substrate specificity of beta-tryptase. To further improve the affinity/selectivity profile of this lead structure, we have now investigated beta-homo-3-aminomethylphenylalanine as S1 ligand. In contrast to the corresponding beta-homo amino acids derived from lysine or arginine, we demonstrate that this particular basic beta-homo amino acid is a privileged S1 ligand for the development of beta-tryptase inhibitors. Besides affinity, selectivity and reduced basicity, these novel cyclotheonamide E4 analogs show excellent stability in human plasma and serum. PMID- 22047803 TI - The effect of the placement and total charge of the basic amino acid clusters on antibacterial organism selectivity and potency. AB - Extensive circular dichroism, isothermal titration calorimetry and induced calcein leakage studies were conducted on a series of antimicrobial peptides (AMPs), with a varying number of Lys residues located at either the C-terminus or the N-terminus to gain insight into their effect on the mechanisms of binding with zwitterionic and anionic membrane model systems. Different CD spectra were observed for these AMPs in the presence of zwitterionic DPC and anionic SDS micelles indicating that they adopt different conformations on binding to the surfaces of zwitterionic and anionic membrane models. Different CD spectra were observed for these AMPs in the presence of zwitterionic POPC and anionic mixed 4:1 POPC/POPG LUVs and SUVs, indicating that they adopt very different conformations on interaction with these two types of LUVs and SUVs. In addition, ITC and calcein leakage data indicated that all the AMPs studied interact via very different mechanisms with anionic and zwitterionic LUVs. ITC data suggest these peptides interact primarily with the surface of zwitterionic LUVs while they insert into and form pores in anionic LUVs. CD studies indicated that these compounds adopt different conformations depending on the ratio of POPC to POPG lipids present in the liposome. There are detectable spectroscopic and thermodynamic differences between how each of these AMPs interacts with membranes, that is position and total charge density defines how these AMPs interact with specific membrane models and thus partially explain the resulting diversity of antibacterial activity of these compounds. PMID- 22047804 TI - Inhibition of rat synaptic membrane Na+/K+-ATPase and ecto-nucleoside triphosphate diphosphohydrolases by 12-tungstosilicic and 12-tungstophosphoric acid. AB - The in vitro influence of Keggin structure polyoxotungstates, 12-tungstosilicic acid, H(4)SiW(12)O(40) (WSiA) and 12-tungstophosphoric acid, H(3)PW(12)O(40) (WPA), and monomer Na(2)WO(4) * 2H(2)O on rat synaptic plasma membrane (SPM) Na(+)/K(+)-ATPase and E-NTPDase activity was studied, whereas the commercial porcine cerebral cortex Na(+)/K(+)-ATPase served as a reference. Dose-dependent Na(+)/K(+)-ATPase inhibition was obtained for all investigated compounds. Calculated IC(50) (10 min) values, in mol/l, for SPM/commercial Na(+)/K(+) ATPase, were: 3.4 * 10(-6)/4.3 * 10(-6), 2.9 * 10(-6)/3.1 * 10(-6) and 1.3 * 10( 3)/1.5 * 10(-3) for WSiA, WPA and Na(2)WO(4) * 2H(2)O, respectively. In the case of E-NTPDase, increasing concentrations of WSiA and WPA induced its activity reduction, while Na(2)WO(4) * 2H(2)O did not noticeably affect the enzyme activity at all investigated concentrations (up to 1 * 10(-3)mol/l). IC(50) (10 min) values, obtained from the inhibition curves, were (in mol/l): 4.1 * 10(-6) for WSiA and 1.6 * 10(-6) for WPA. Monolacunary Keggin anion was found as the main active molecular species present under physiological conditions (in the enzyme assays, pH 7.4), for the both polyoxotungstates solutions (1 mmol/l), using Fourier transform infrared (FT-IR) and micro-Raman spectroscopy. Additionally, commercial porcine cerebral cortex Na(+)/K(+)-ATPase was exposed to the mixture of Na(2)WO(4) * 2H(2)O and WSiA at different concentrations. Additive inhibition effect was achieved for lower concentrations of Na(2)WO(4) * 2H(2)O/WSiA (<= 1 * 10(-3)/4 * 10(-6) mol/l), while antagonistic effect was obtained for all higher concentrations of the inhibitors. PMID- 22047805 TI - Synthesis of macrolones with central piperazine ring in the linker and its influence on antibacterial activity. AB - Three macrolides, clarithromycin, azithromycin and 11-O-Me-azithromycin have been selected for the construction of a series of new macrolone derivatives. Quinolone linker intermediates are prepared by Sonogashira-type C(6)-alkynylation of 6 iodoquinolone precursors. The final macrolones, differing by macrolide moiety and substituents at the position N-1 of the quinolone or by the presence of an ethyl ester or free acid on the quinolone unit attached via a linker. The linker comprises of a central piperazine ring bonded to the 4"-O position of cladinose by 3-carbon ester or ether functionality. Modifications of the linker did not improve antibacterial properties compared to the previously reported macrolone compounds. Linker flexibility seems to play an important role for potency against macrolide resistant respiratory pathogens. PMID- 22047806 TI - Feasibility of TCP-based dose painting by numbers applied to a prostate case with (18)F-choline PET imaging. AB - INTRODUCTION: A biologically adaptive radiation treatment method to maximize the TCP is shown. Functional imaging is used to acquire a heterogeneous dose prescription in terms of Dose Painting by Numbers and to create a patient specific IMRT plan. METHOD AND MATERIALS: Adapted from a method for selective dose escalation under the guidance of spatial biology distribution, a model, which translates heterogeneously distributed radiobiological parameters into voxelwise dose prescriptions, was developed. At the example of a prostate case with (18)F-choline PET imaging, different sets of reported values for the parameters were examined concerning their resulting range of dose values. Furthermore, the influence of each parameter of the linear-quadratic model was investigated. A correlation between PET signal and proliferation as well as cell density was assumed. Using our in-house treatment planning software Direct Monte Carlo Optimization (DMCO), a treatment plan based on the obtained dose prescription was generated. Gafchromic EBT films were irradiated for evaluation. RESULTS: When a TCP of 95% was aimed at, the maximal dose in a voxel of the prescription exceeded 100Gy for most considered parameter sets. One of the parameter sets resulted in a dose range of 87.1Gy to 99.3Gy, yielding a TCP of 94.7%, and was investigated more closely. The TCP of the plan decreased to 73.5% after optimization based on that prescription. The dose difference histogram of optimized and prescribed dose revealed a mean of -1.64Gy and a standard deviation of 4.02Gy. Film verification showed a reasonable agreement of planned and delivered dose. CONCLUSION: If the distribution of radiobiological parameters within a tumor is known, this model can be used to create a dose-painting by numbers plan which maximizes the TCP. It could be shown, that such a heterogeneous dose distribution is technically feasible. PMID- 22047807 TI - Specialized connective tissue: bone, the structural framework of the upper extremity. AB - Bone is a connective tissue containing cells, fibers, and ground substance. There are many functions in the body in which the bone participates, such as storing minerals, providing internal support, protecting vital organs, enabling movement, and providing attachment sites for muscles and tendons. Bone is unique because its collagen framework absorbs energy, whereas the mineral encased within the matrix allows bone to resist deformation. This article provides an overview of the structure and function of bone tissue from a macroscopic to microscopic level and discusses the physiological processes contributing to upper extremity bone health. It concludes by discussing common conditions influencing upper extremity bone health. PMID- 22047808 TI - Ischemia induces P-selectin-mediated selective progenitor cell engraftment in the isolated-perfused heart. AB - Clinical trials infusing Bone Marrow Cells (BMCs) into injured hearts have produced measureable improvements in cardiac performance, but were insufficient to improve patient outcomes. Low engraftment rates are cited as probable contributor to limited improvements. To understand the mechanisms that control myocardial engraftment of BMCs following ischemia-reperfusion injury, in isolated perfused mouse hearts, stop-flow ischemia was followed by variable-duration reperfusion (0-60 min) before addition of labeled syngenic BMCs to the perfusate. After a buffer-only wash, the heart was disaggregated. Retained BMCs (digest) and infused BMCs (aliquot) were compared by flow cytometry for c-kit and CD45 expression to determine the proportion of cell subtypes engrafted versus delivered (selectivity ratio). In these studies, a time-dependent selective retention of c-kit(+) cells was apparent starting at 30 min of reperfusion, at which time c-kit(+)/CD45(+) BMCs showed a selectivity ratio of 18 +/- 2 (versus 2 +/- 1 in sham-ischemic controls). To study the underlying mechanism for this selective retention, neutralizing antibodies for P-selectin or L-selectin were infused into the heart preparation and incubated with BMCs prior to BMC infusion. Blocking P-selectin in ischemic hearts ablated selectivity for c-kit(+)/CD45(+) BMCs at 30 min reperfusion (selectivity ratio of 3 +/- 1) while selectivity persisted in the presence of L-selectin neutralization (selectivity ratio of 17 +/- 2). To corroborate this finding, a parallel plate flow chamber was used to study capture and rolling dynamics of purified c-kit(+) versus c-kit- BMCs on various selectin molecules. C-kit(+) BMCs interacted weakly with L-selectin substrates (0.03 +/- 0.01% adhered) but adhered strongly to P-selectin (0.28+/ 0.04% adhered). C-kit- BMCs showed intermediate binding regardless of substrate (0.18 +/- 0.04% adhered on L-selectin versus 0.17 +/- 0.04% adhered on P selectin). Myocardial ischemia-reperfusion stress induces selective engraftment of c-kit(+) bone marrow progenitor cells via P-selectin activation. PMID- 22047809 TI - The impact of the stopping rule on sex ratio of last births in Vietnam. AB - This study examines the hypothesis that the stopping rule - a traditional postnatal sex selection method where couples decide to cease childbearing once they bear a son - plays a role in high sex ratio of last births (SRLB). The study develops a theoretical framework to demonstrate the operation of the stopping rule in a context of son preference. This framework was used to demonstrate the impact of the stopping rule on the SRLB in Vietnam, using data from the Population Change Survey 2006. The SRLB of Vietnam was high at the level of 130 in the period 1970-2006, and particularly in the period 1986-1995, when sex selective abortion was not available. Women were 21% more likely to stop childbearing after a male birth compared with a female birth. The SRLB was highest at parity 2 (138.7), particularly in rural areas (153.5), and extremely high (181.9) when the previous birth was female. Given the declining fertility, the stopping rule has a potential synergistic effect with sex-selective abortion to accentuate a trend of one-son families in the population. PMID- 22047810 TI - Website quality, expectation, confirmation, and end user satisfaction: the knowledge-intensive website of the Korean National Cancer Information Center. AB - BACKGROUND: The fact that patient satisfaction with primary care clinical practices and physician-patient communications has decreased gradually has brought a new opportunity to the online channel as a supplementary service to provide additional information. OBJECTIVE: In this study, our objectives were to examine the process of cognitive knowledge expectation-confirmation from eHealth users and to recommend the attributes of a "knowledge-intensive website.". Knowledge expectation can be defined as users' existing attitudes or beliefs regarding expected levels of knowledge they may gain by accessing the website. Knowledge confirmation is the extent to which user's knowledge expectation of information systems use is realized during actual use. In our hypothesized research model, perceived information quality, presentation and attractiveness as well as knowledge expectation influence knowledge confirmation, which in turn influences perceived usefulness and end user satisfaction, which feeds back to knowledge expectation. METHODS: An empirical study was conducted at the National Cancer Center (NCC), Republic of Korea (South Korea), by evaluating its official website. A user survey was administered containing items to measure subjectively perceived website quality and expectation-confirmation attributes. A study sample of 198 usable responses was used for further analysis. We used the structural equation model to test the proposed research model. RESULTS: Knowledge expectation exhibited a positive effect on knowledge confirmation (beta = .27, P < .001). The paths from information quality, information presentation, and website attractiveness to knowledge confirmation were also positive and significant (beta = .24, P < .001; beta = .29, P < .001; beta = .18, P < .001, respectively). Moreover, the effect of knowledge confirmation on perceived usefulness was also positively significant (beta = .64, P < .001). Knowledge expectation together with knowledge confirmation and perceived usefulness also significantly affected end user satisfaction (beta = .22 P < .001; beta = .39, P < .001; beta = .25, P < .001, respectively). CONCLUSIONS: Theoretically, this study has (1) identified knowledge-intensive website attributes, (2) enhanced the theoretical foundation of eHealth from the information systems (IS) perspective by adopting the expectation-confirmation theory (ECT), and (3) examined the importance of information and knowledge attributes and explained their impact on user satisfaction. Practically, our empirical results suggest that perceived website quality (ie, information quality, information presentation, and website attractiveness) is a core requirement for knowledge building. In addition, our study has also shown that knowledge confirmation has a greater effect on satisfaction than both knowledge expectation and perceived usefulness. PMID- 22047811 TI - Pharmacokinetics, pharmacodynamics, and comparative bioavailability of single, oral 2-mg doses of dexamethasone liquid and tablet formulations: a randomized, controlled, crossover study in healthy adult volunteers. AB - BACKGROUND: Dexamethasone is a glucocorticoid used widely worldwide for immunosuppressive treatment, allergies, bronchiolitis, and croup, among others. For children, liquid formulations are especially suitable because, compared with other dosage forms, both exact dosing and proper intake are facilitated. OBJECTIVE: The objective was to evaluate the pharmacokinetics, pharmacodynamics, and comparative bioavailability of a commercial liquid oral dexamethasone formulation intended for pediatric use relative to those of a tablet. METHODS: In a randomized, controlled, crossover study in 24 healthy adult volunteers, we administered single doses of the liquid and tablet formulation, containing 2 mg of dexamethasone each. Blood samples were taken up to 24 hours postdose. Quantification was carried out using a validated specific and sensitive high pressure liquid chromatography with UV detector method. Noncompartmental pharmacokinetic parameters were compared between treatments according to European Medicines Agency (EMA) bioequivalence guidelines. For AUC(0-t) and C(max), the 90% CI for the ratio of the test and reference products should be contained within the predetermined acceptance interval of 80% to 125%. As a pharmacodynamic variable, we measured suppression of endogenous cortisol (predose and postdose). RESULTS: Both preparations showed similar pharmacokinetic and pharmacodynamic profiles but high between-subject variability of pharmacokinetic key parameters and endogenous cortisol concentrations (>30%). Mean AUC(0-t), AUC(0-infinity), and C(max) were 37.8 ng/mL/h, 46.0 ng/mL/h, and 9.35 ng/mL, respectively, for the liquid and 41.3 ng/mL/h, 48.1 ng/mL/h, and 9.17 ng/mL, respectively, for the tablet formulation. T(max) was 0.89 hour (liquid) and 0.97 hour (tablet). The point estimates and 90% CIs for AUC(0-t), AUC(0-infinity), and C(max) ratios (liquid vs tablet) were 91.42% (82.05%-101.86%), 95.72% (84.46%-108.5%), and 102.04% (86.94%-119.76%), respectively. Thus, point estimates and 90% CIs were within the bioequivalence range of 80% to 125% for all relevant parameters, including the pharmacodynamic parameter AUEC (area under the effect curve). CONCLUSIONS: This single-dose study suggests that the test and reference products met the EMA regulatory criteria to assume bioequivalence in these fasting healthy male and female volunteers. German Register of Clinical Trials registration number: DRKS00000785. PMID- 22047812 TI - Tolerability and pharmacokinetics of lobeglitazone (CKD-501), a peroxisome proliferator-activated receptor-gamma agonist: a single- and multiple-dose, double-blind, randomized control study in healthy male Korean subjects. AB - BACKGROUND: Lobeglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist with partial PPAR-alpha affinity, was developed to treat type 2 diabetes mellitus. OBJECTIVE: This study's aim was to evaluate the tolerability and pharmacokinetic (PK) properties of lobeglitazone to satisfy regulatory requirements for marketing approval in Korea. METHODS: A block randomized, double-blind, placebo-controlled, single- and multiple-dose study was conducted in healthy subjects. In the pilot study, 4 subjects were administered 0.5 mg, including 1 receiving a placebo. Then, the single-dose study was conducted with 1, 2, 4, and 8 mg doses (8 subjects in each group, including 2 receiving placebos), followed by the multiple-dose study with 1, 2, and 4 mg doses (once daily for 7 days; 8 subjects in each group, including 2 receiving placebos). Serial samples of blood and urine were collected and drug concentrations were determined by high turbulence liquid chromatography-LC/MS/MS. Tolerability assessments were performed throughout the study. Adverse events (AEs) were determined from general health-related questions and self-reports. RESULTS: Thirty-six (mean [SD]; age, 23.6 [2.7] years; weight, 70.0 [6.9] kg) and 25 Korean male subjects (age, 23.5 [3.1] years; weight 69.4 [9.4] kg) were enrolled in the single- and multiple-dose studies, respectively. The data from subjects administered lobeglitazone who completed the study (27, single; 18, multiple) was included in the PK analyses. In the single-dose study, the AUC and C(max) of lobeglitazone increased with the dose. After repeated dosing for 7 days, the accumulation ratio ranged from 1.1 to 1.4. A total of 25 AEs were reported by 11 (30.6%) and 8 subjects (33.3%) in the single- and multiple-dose studies, respectively. All AEs were mild in intensity and not serious. CONCLUSIONS: Lobeglitazone was well tolerated in this small, selected group of healthy male Korean volunteers. The AUC and C(max) of lobeglitazone increased in a dose-proportional manner from 1 to 4 mg. PMID- 22047813 TI - Clinical review: use of venous oxygen saturations as a goal - a yet unfinished puzzle. AB - Shock is defined as global tissue hypoxia secondary to an imbalance between systemic oxygen delivery and oxygen demand. Venous oxygen saturations represent this relationship between oxygen delivery and oxygen demand and can therefore be used as an additional parameter to detect an impaired cardiorespiratory reserve. Before appropriate use of venous oxygen saturations, however, one should be aware of the physiology. Although venous oxygen saturation has been the subject of research for many years, increasing interest arose especially in the past decade for its use as a therapeutic goal in critically ill patients and during the perioperative period. Also, there has been debate on differences between mixed and central venous oxygen saturation and their interchangeability. Both mixed and central venous oxygen saturation are clinically useful but both variables should be used with insightful knowledge and caution. In general, low values warn the clinician about cardiocirculatory or metabolic impairment and should urge further diagnostics and appropriate action, whereas normal or high values do not rule out persistent tissue hypoxia. The use of venous oxygen saturations seems especially useful in the early phase of disease or injury. Whether venous oxygen saturations should be measured continuously remains unclear. Especially, continuous measurement of central venous oxygen saturation as part of the treatment protocol has been shown a valuable strategy in the emergency department and in cardiac surgery. In clinical practice, venous oxygen saturations should always be used in combination with vital signs and other relevant endpoints. PMID- 22047814 TI - Identification and in vitro screening of avian yeasts for use as probiotic. AB - The objective of this study was to isolate and identify yeast strains from broilers excreta and to evaluate in vitro their potential for probiotic use in animal production. METHODS AND RESULTS: Nine yeast strains were isolated and presumptively pre-identified by biochemical assays. These isolates were grouped in six different molecular profiles using PCR-fingerprinting technique. Each profile was identified by sequencing of the D1/D2 domains of the large subunit of the 26S rRNA gene. These yeasts were identified as: Trichosporon sp. (LV-2), Wickerhamomyces anomalus (LV-6), Pichia kudriavzevii (LV-8), Kodamaea ohmeri (LV 9) and Trichosporon asahii (LV-10). A pre-screening of the strains for probiotic use was based on their ability to agglutinate pathogenic micro-organisms. These yeast strains were characterized for specific growth rate, duplication time, their cell surface hydrophobicity, medium acidification, resistance to low pH (2.0, 2.5 and 3.0) and concentrations of bile salts (0.3% and 0.6%). The isolate of W. anomalus (LV-6) had the highest agglutinating and adherence capacity, a growth rate of 2.07*10(8) cfu/mL in 24 h at 30 degrees C, decreasing the medium pH from 6.5 to 5.23, a 25% hydrophobicity and an elevated capacity to grow under stress conditions. CONCLUSIONS: W. anomalus strain LV-6 showed the best characteristics for use as a probiotic candidate. SIGNIFICANCE AND IMPACT OF THE STUDY: The data from this study helped in choosing a probiotic candidate from yeast to use in broiler production. PMID- 22047815 TI - Effect of intravenous dose escalation with alfaxalone and propofol on occurrence of apnoea in the dog. AB - Spontaneous ventilation after induction of anaesthesia with intravenous alfaxalone or propofol was evaluated in a dose escalation study using 6 dogs. Each dog was dosed at 1*, 2*, 5*, 10* and 20* multiples of the labelled doses (2mg/kg for alfaxalone; 6.5mg/kg for propofol), until apnoea was observed. For each administration, the entire calculated dose was delivered over 1 min. All 6 dogs ventilated spontaneously after labelled (1*) doses of each drug but became apnoeic at 5* dose of propofol versus 20* dose of alfaxalone. For propofol at 2* and 5* doses, 4 and 0 dogs ventilated spontaneously respectively. For alfaxalone at 2*, 5* and 10* doses all 6, 4 and 1 dog ventilated spontaneously, respectively. The median dose which induced apnoea was higher for alfaxalone (5*) than for propofol (2*) (p=0.05). We concluded that induction of anaesthesia with propofol is more likely to induce apnoea than with alfaxalone. PMID- 22047816 TI - Helminth fauna of a turtle species introduced in Japan, the red-eared slider turtle (Trachemys scripta elegans). AB - The red-eared slider turtle (Trachemys scripta elegans) was intentionally introduced from the United States to Japan as a pet in the 1950s and has become established throughout much of the country. We examined red-eared slider turtles from two localities in Japan for foreign parasitic helminths. Consequently, a total of seven species of helminths were found: two monogeneans (Neopolystoma exhamatum and Polystomoides japonicum), three digeneans (Spirorchisartericola, Spi.elegans and Telorchis clemmydis) and two nematodes (Serpinema microcephalum and Falcaustra wardi). Of these, three helminths are alien to Japan Spi.artericola, Spi. elegans and F. wardi-which represent the first report of their presence in the red-eared slider turtle from Japan. PMID- 22047817 TI - Effects of sedation with acepromazine maleate and buprenorphine hydrochloride on femoral artery blood flow in healthy dogs. AB - The purpose of this study was to qualify and quantify the femoral artery blood flow by duplex Doppler ultrasonography (DDU) in healthy dogs, before and after the administration of a combination of acepromazine maleate and buprenorphine hydrochloride (ACP-BPN). Seven healthy adult mongrel dogs and three adult beagles were used. Heart rate, arterial blood pressure and measurement of femoral artery blood flow by DDU were also recorded. The DDU measurements were: femoral artery diameter (FAD), peak systolic velocity (PSV), early retrograde (EDV) and end diastolic velocities (EnDV), mean velocity (BMV), pulsatility index (PI), flow velocity integral (FVI) and femoral blood flow (FBF). After 30 min, combination ACP-BPN was administered intramuscularly, and all the measurements were recorded again. The ACP-BPN protocol induced a significant decrease in systolic, mean, and diastolic arterial blood pressure, and heart rate. A significant increase in peak systolic velocity and integral flow velocity integral of the femoral blood were obtained. The Doppler spectra of the blood flow in the femoral artery revealed a spectral dispersion pattern after ACP-BPN administration in all the dogs. These results demonstrate that despite quantitative and qualitative changes, the overall femoral blood flow (FBF) is not significantly modified. PMID- 22047818 TI - A newly established bovine intestinal epithelial cell line is effective for in vitro screening of potential antiviral immunobiotic microorganisms for cattle. AB - We evaluated whether a bovine intestinal epithelial (BIE) cell line could serve as a useful in vitro model system for studying antiviral immune responses in bovine intestinal epithelial cells (IECs) and for the primary screening of immunobiotic microorganisms with antiviral protective capabilities. Immunofluorescent analyses revealed that toll-like receptor 3 (TLR3) was expressed in BIE cells, and the results of real-time quantitative PCR showed that these cells respond to stimulation with poly(I:C) by up-regulating pro inflammatory cytokines and type I interferons. In addition, we demonstrated that BIE cells are useful for the primary screening of immunobiotic lactic acid bacteria strains which are able to beneficially modulate antiviral immune responses triggered by TLR3 activation in bovine IECs. The characterization of BIE cells performed in the present study represents an important step towards the establishment of a valuable bovine in vitro system that could be used for the development of immunomodulatory feed for bovine hosts. PMID- 22047819 TI - Ultrasound-assisted emulsification-microextraction for the sensitive determination of Brett character responsible compounds in wines. AB - In this study, a method based on ultrasound-assisted emulsification microextraction (USAEME) was optimised for the determination of Brett character responsible compounds (4-ethylguaiacol (EG), 4-ethylphenol (EP), 4-vinylguaiacol (VG) and 4-vinylphenol (VP)) in wines. For this purpose, once the extraction solvent had been selected, the influence on the extraction efficiency of ratio between extraction solvent and sample volumes, temperature, ionic strength and time was studied using experimental design methodology. The optimum conditions found for USAEME of 5mL of wine were 160MUL of chlorobenzene at 60 degrees C during 5min without salt addition. Then, the analytical performance of the optimised USAEME procedure was evaluated. For all the studied compounds, the proposed method showed correlation coefficients over 0.984. Satisfactory repeatability (below 10%) and inter-day repeatability (below 11%) were obtained at different concentration levels and the method achieved detection limits similar or even lower than previously reported for these compounds in wines. Moreover, the applicability of the method was evaluated by the analysis of real samples. To our knowledge, this is the first time that USAEME has been applied to the determination of Brett character responsible compounds in wine. PMID- 22047820 TI - Surface-functionalized electrospun carbon nanofiber mats as an innovative type of protein adsorption/purification medium with high capacity and high throughput. AB - Due to recent advances in the production of biotherapeutics, high capacity, high throughput adsorption media for efficient and economic separation of these medically important products are in great demand. One option that has been evaluated extensively is membrane/mat adsorption. While these media allow for rapid adsorption (due to the decreased internal diffusion) and high throughput processing (due to the open porous structure), they often suffer from low capacity and poor enrichment factors. Herein, we report the fabrication, characterization, and protein adsorption evaluation of an innovative type of membrane/mat adsorption media based on electrospun carbon nanofibers. By surface functionalization of these nanofibers with a weak acid cation-exchange ligand, the capacity was doubled for binding a model protein (i.e., lysozyme) compared to commercial products; and the capacity value was over 200 mg lysozyme per gram of adsorption media. Meanwhile, the thin nanofibers (having diameters of ~300 nm) along with open pores among nanofibers in the mats (having sizes of ~10-15 MUm) allowed for higher operating flow rates and lower pressure drops. Furthermore, the incorporation of higher ligand density and the addition of a non-ionic surfactant (i.e., Triton X-305) into the adsorption buffer eliminated the non specific binding of a competing protein (bovine serum albumin). In combination, this study suggested that electrospun carbon nanofiber adsorption media would provide a promising alternative to packed resin beds for bioseparations. PMID- 22047821 TI - Analysis of therapeutic peptides in human urine by combination of capillary zone electrophoresis-electrospray mass spectrometry with preparative capillary isotachophoresis sample pretreatment. AB - The presented study deals with the off-line coupling of preparative isotachophoresis (pITP) with on-line combination of capillary zone electrophoresis with electrospray mass spectrometric detection (CZE-ESI-MS) used for the analysis of therapeutic peptides (anserine, carnosine, and buserelin) in complex matrix (urine). Preparative capillary isotachophoresis, operating in a discontinuous fractionation mode in column-coupling configuration, served as a sample pretreatment technique to separation, and fractionation of mixture of therapeutic peptides present in urine at low concentration level. The fractions isolated by pITP procedure were subsequently analyzed by capillary zone electrophoresis with electrospray mass spectrometric detection. Acetic acid at 200 mmol L(-1) concentration served as background electrolyte in CZE stage and it is compatible with MS detection in positive ionization mode. In pITP fractionation procedure, sodium cation (10 mmol L(-1) concentration) as leading ion and beta-alanine as terminating ion (20 mmol L(-1) concentration) were used. While using CZE-ESI-MS, the limits of detection were 0.18 MUg mL(-1) for carnosine, 0.17 MUg mL(-1) for anserine and 0.64 MUg mL(-1) for buserelin in water and 0.19 MUg mL(-1) for carnosine, 0.50 MUg mL(-1) for anserine and 0.74 MUg mL(-1) for buserelin in 10 times diluted urine, respectively. The cleaning power of pITP sample pretreatment was proved as the peptides provided the higher MS signals at lower concentration levels resulting from the minimized matrix effects. The quality of obtained MS/MS spectra was very good so that they can provide information about the structure of analytes, and they were used for verification of the analytes identities. The pITP pretreatment improved the detection limits of the analyzed therapeutic peptides at least 25 times compared to the CZE-ESI-MS itself. PMID- 22047822 TI - The association between vitamin K antagonist therapy and site-specific cancer incidence estimated by using heart valve replacement as an instrumental variable. AB - Earlier studies suggest a protective association between vitamin K antagonist (VKA) anticoagulants and the incidence of cancer. The authors examined the associations between VKA therapy and incidence of 24 site-specific cancers with a Danish population-based cohort study, using heart valve replacement as an instrumental variable. The authors enrolled 9,727 Danish residents who received a replacement heart valve between 1989 and 2006. The heart valve recipients were matched with 95,481 unexposed individuals on age and sex. The authors used the heart valve replacement instrument to estimate rate ratios associating VKA therapy with incidence of the 24 site-specific cancers using Poisson regression models. Direct associations between VKA therapy and incidence of the 24 cancers were estimated in a prescription validation subset. The instrumental variable associations were plotted according to the inverse normal of rank percentile and subjected to semi-Bayes shrinkage adjustment for multiple comparisons. The pattern of associations was consistent with a null-centered Gaussian distribution. No individual cancer site showed a substantial positive or negative association with VKA therapy in the prescription validation subset, the instrumental variable analysis, or the analysis with semi-Bayes adjustment. These results do not support the existing hypothesis that VKA therapy is associated with reduced cancer risk. PMID- 22047823 TI - Lagging exposure information in cumulative exposure-response analyses. AB - Lagging exposure information is often undertaken to allow for a latency period in cumulative exposure-disease analyses. The authors first consider bias and confidence interval coverage when using the standard approaches of fitting models under several lag assumptions and selecting the lag that maximizes either the effect estimate or model goodness of fit. Next, they consider bias that occurs when the assumption that the latency period is a fixed constant does not hold. Expressions were derived for bias due to misspecification of lag assumptions, and simulations were conducted. Finally, the authors describe a method for joint estimation of parameters describing an exposure-response association and the latency distribution. Analyses of associations between cumulative asbestos exposure and lung cancer mortality among textile workers illustrate this approach. Selecting the lag that maximizes the effect estimate may lead to bias away from the null; selecting the lag that maximizes model goodness of fit may lead to confidence intervals that are too narrow. These problems tend to increase as the within-person exposure variation diminishes. Lagging exposure assignment by a constant will lead to bias toward the null if the distribution of latency periods is not a fixed constant. Direct estimation of latency periods can minimize bias and improve confidence interval coverage. PMID- 22047824 TI - Survival in population-based pancreatic cancer patients: San Francisco Bay area, 1995-1999. AB - Patient vital status generally is passively obtained by cancer registries, and no previous population-based studies have used extensive active follow-up to compute a more accurate overall survival rate for pancreatic cancer. Therefore, the authors used multiple active and passive follow-up methods to determine vital status and date of death for 1,954 pancreatic cancer patients diagnosed from 1995 to 1999 in a large population-based study in the San Francisco Bay Area, California. Survival rates were estimated by using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals were estimated by using multivariable Cox proportional-hazards models. Vital status was confirmed for >99% of 1,954 patients. The overall 5-year survival rate was 1.3% and was greater in patients who were younger and who had localized disease, well-differentiated tumors, and surgical resection. Shorter survival was associated with older age at diagnosis, male sex, distant/metastatic disease, and poorly differentiated tumors. Longer survival was observed for Asian/Pacific Islanders compared with non-Hispanic whites and for any active treatment regardless of tumor stage. With an almost complete follow-up, the authors observed a low overall 5-year survival rate. Although the results provide further evidence of poor survival among patients with pancreatic cancer, the data also suggest that within-stage-of-disease patients survived somewhat longer with therapy. PMID- 22047825 TI - Nitrosatable drug exposure during early pregnancy and neural tube defects in offspring: National Birth Defects Prevention Study. AB - Nitrosatable drugs, such as secondary or tertiary amines and amides, form N nitroso compounds in the presence of nitrite. Various N-nitroso compounds have been associated with neural tube defects in animal models. Using data from the National Birth Defects Prevention Study, the authors examined nitrosatable drug exposure 1 month before and 1 month after conception in 1,223 case mothers with neural tube defect-affected pregnancies and 6,807 control mothers who delivered babies without major congenital anomalies from 1997 to 2005. Nitrite intakes were estimated from mothers' responses to a food frequency questionnaire. After adjustment for maternal race/ethnicity, educational level, and folic acid supplementation, case women were more likely than were control women to have taken tertiary amines (odds ratio = 1.60, 95% confidence interval (CI): 1.31, 1.95). This association was strongest with anencephalic births (odds ratio = 1.96, 95% CI: 1.40, 2.73); odds ratios associated with tertiary amines from the lowest tertile of nitrite intake to the highest tertile were 1.16 (95% CI: 0.59, 2.29), 2.19 (95% CI: 1.25, 3.86), and 2.51 (95% CI: 1.45, 4.37), respectively. Odds ratios for anencephaly with nitrosatable drug exposure were reduced among women who also took daily vitamin supplements that contained vitamin C. Prenatal exposure to nitrosatable drugs may increase the risk of neural tube defects, especially in conjunction with a mother's higher dietary intake of nitrites, but vitamin C might modulate this association. PMID- 22047826 TI - Using regression calibration equations that combine self-reported intake and biomarker measures to obtain unbiased estimates and more powerful tests of dietary associations. AB - The authors describe a statistical method of combining self-reports and biomarkers that, with adequate control for confounding, will provide nearly unbiased estimates of diet-disease associations and a valid test of the null hypothesis of no association. The method is based on regression calibration. In cases in which the diet-disease association is mediated by the biomarker, the association needs to be estimated as the total dietary effect in a mediation model. However, the hypothesis of no association is best tested through a marginal model that includes as the exposure the regression calibration-estimated intake but not the biomarker. The authors illustrate the method with data from the Carotenoids and Age-Related Eye Disease Study (2001--2004) and show that inclusion of the biomarker in the regression calibration-estimated intake increases the statistical power. This development sheds light on previous analyses of diet-disease associations reported in the literature. PMID- 22047827 TI - Single-layer Integra for one-stage reconstruction of scalp defects with exposed bone following full-thickness burn injury: a novel technique. PMID- 22047828 TI - A systematic review of the quality of burn scar rating scales for clinical and research use. AB - INTRODUCTION: Scar rating scales have the potential to contribute to better evaluation of scar properties in both research and clinical settings. Despite a large number of scars assessment scales being available, there is limited information regarding the clinimetric properties of many of these scales. The purpose of the review was to inform clinical and research practice by determining the quality and appropriateness of existing scales. This review summarises the available evidence for the clinimetric properties of reliability, validity (including responsiveness), interpretability and feasibility of existing scales. METHODS: Electronic searches of MEDLINE, CINAHL, EMBASE and The Cochrane Library databases from 1990 onwards were used to identify English articles related to burn scar assessment scales. Scales were critically reviewed for clinimetric properties that were reported in, but not necessarily the focus of studies. RESULTS: A total of 29 studies provided data for 18 different scar rating scales. Most scar rating scales assessed vascularity, pliability, height and thickness. Some scales contained additional items such as itch. Only the Patient and Observer Scar Assessment Scale (POSAS) received a high quality rating but only in the area of reliability for total scores and the subscale vascularity. The Vancouver Scar Scale (VSS) received indeterminate ratings for construct validity, reliability and responsiveness. Where evidence was available, all other criteria for the POSAS, VSS and the remaining 17 scales received an indeterminate rating due to methodological issues, or a low quality rating. Poorly defined hypotheses limited the ability to give a high quality rating to data pertaining to construct validity, responsiveness and interpretability. No scale had empirical testing of content validity and no scale was of sufficient quality to consider criterion validity. CONCLUSIONS: The POSAS, with high quality reliability but indeterminate validity, was considered to be superior in performance based on existing evidence. The VSS had the most thorough review of clnimetrics although available data received indeterminate quality ratings. On the basis of the evidence, the use of total scores has not been supported, nor has the measurement of pigmentation using a categorical scale. PMID- 22047829 TI - Hybrid repair of thoracic aortic lesions for zone 0 and 1 in high-risk patients. AB - PURPOSE: Some patients with aortic arch or descending thoracic aorta pathologies are not suited for open repair because of comorbidities that may increase their risk of procedural complications or death. Endovascular approaches may also be difficult when there are inadequate proximal landing zones in the aortic arch. We report our experience using rerouting techniques with bypass, stenting of the branches, or a combination of both to create a landing area in zones 0 and 1 of the aortic arch. METHODS: Since November 2002, thoracic aortic endoluminal grafts were placed in 38 patients in whom the endograft was deployed in zone 0 (n = 27) or zone 1 (n = 11). A retrospective review is included. RESULTS: There were 11 women and 27 men with a mean age of 65.4 years (range 38-88). Aortic pathology included 12 Stanford type A dissections, 10 aortic arch aneurysms, 8 Stanford type B dissections, 3 descending thoracic aortic aneurysms, 2 aortobronchial fistulas, 1 innominate artery aneurysm and 2 aortic arch pseudoaneurysms. In zone 0, 21 had thoracic debranching with an ascending bypass, three patients had a remote-inflow and three patients had a chimney-stent with carotid-carotid bypass. In zone 1, five patients had a carotid-carotid bypass, one patient had an aortic to left common carotid artery (LCCA) bypass and five patients had chimney-stent on the LCCA. Fifty-eight percent of the patients were symptomatic and 26% emergent. Three patients required hemodialysis postoperatively (7.9%), 18 patients (47.4%) required prolonged mechanical ventilation for respiratory insufficiency. Paraplegia occurred in one patient (2.7%), and five patients suffered a cerebrovascular accident (13.1%). There were four early type I and two type II endoleaks. Overall 30-day mortality was 23.7%. CONCLUSIONS: The hybrid approach for repair of the aortic arch pathologies is feasible in patients unfit for open repair. We present the results of performing different techniques to treat the aortic arch with hybrid repair with antegrade or retrograde inflow, stenting of the branches or a combination of both. Long-term results are unknown, and larger series results and comparative studies are needed to determine safety and efficacy. PMID- 22047830 TI - Presentation, complications, and natural history of penetrating atherosclerotic ulcer disease. AB - OBJECTIVES: Increased utilization of computed tomography angiography (CTA) has increased the radiologic diagnosis of penetrating atherosclerotic ulcers (PAUs), which are defined as the ulceration of atherosclerotic plaque through the internal elastic lamina into the aortic media. However, the presentation, treatment indications, and natural history of this disease process remain unclear. METHODS: The radiology database at a single university hospital was searched retrospectively for the CTA diagnosis of PAU from January 2003 to June 2009. All scans were interpreted by a cardiovascular radiologist. Information on PAU characteristics and need for surgical repair due to PAU disease was collected. PAU stability or progression was assessed by follow-up CTA, if available. Only PAUs in the aortic arch, descending thoracic aorta, and abdominal aorta were included. RESULTS: Three hundred eighty-eight PAUs were diagnosed by CTA interpretation. PAU location was in the aortic arch in 27 (6.8%) cases, the descending thoracic aorta in 243 (61.2%) cases, and the abdominal aorta in 118 (29.7%) cases. Two hundred twenty-four (57.7%) PAUs were isolated (without saccular aneurysm or intramural hematoma); 108 (27.8%) PAUs had associated saccular aneurysms; and 56 (14.4%) PAUs had associated intramural hematoma. Rupture was present in 16 (4.1%) cases. Fifty (12.9%) PAUs underwent repair with thoracic endovascular aortic repair (TEVAR) (n = 30), endovascular aneurysm repair (EVAR) (n = 10), or open surgery (n = 10); primary indications for repair were saccular aneurysm (n = 26), rupture (n = 16), and persistent or recurrent symptoms (n = 8). Even if initially treated conservatively with resolution of pain, symptomatic PAU disease was more likely to require repair than asymptomatic PAU disease (36.2% vs 7.8%, P < .001). Follow-up CTA was available for 87 PAUs, 20 (23.0%) of which demonstrated radiographic disease progression at a mean follow-up of 8.4 +/- 10.3 months. Symptomatic PAU disease was more likely to progress than asymptomatic disease (42.9% vs 16.7%, P = .029). CONCLUSIONS: For PAUs diagnosed on CTA at a single institution, 4.1% were ruptured and 12.9% underwent repair. Close follow-up imaging appears to be indicated for PAUs, particularly in the case of symptomatic disease, which is more likely to require repair and to undergo radiographic progression. PMID- 22047831 TI - Ruptured thoracoabdominal aneurysm in a 27-year-old with hyper IgE syndrome. AB - Hyperimmunoglobulin E syndrome is a rare primary immunodeficiency disorder defined by high serum immunoglobulin E titers and associated with characteristic infectious, dermatologic, skeletal, and dental abnormalities. We present the case of a 27-year-old man presenting acutely with a ruptured type IV thoracoabdominal aortic aneurysm. He was successfully treated by open operative repair and discharged with long-term prophylactic antibiotics. To our knowledge, this is the first such case reported in the English literature. PMID- 22047832 TI - Endovascular repair of an internal mammary artery aneurysm in a patient with Loeys-Dietz syndrome. AB - Loeys-Dietz syndrome is a condition that predisposes the development of central and peripheral arterial aneurysms and dissections. The standard approach for treatment of these lesions has been open repair. We present the case of a 34-year old woman with a previous history of multiple open aortic repairs who presented with a right large internal mammary artery aneurysm. The patient was successfully treated with endovascular coil embolization. This case report demonstrates the feasibility of using endovascular interventions to treat unusual aneurysms in patients with Loeys-Dietz syndrome. PMID- 22047833 TI - Evaluation of quality of life over time among 453 patients with hyperhidrosis submitted to endoscopic thoracic sympathectomy. AB - OBJECTIVES: Current data do not provide enough information on how quality of life (QoL) evolves over time in cases of endoscopic thoracic sympathectomy (ETS). The purpose of this study was to ascertain whether the immediate improvement in QoL after the surgery was sustained until the fifth postoperative year. METHODS: This was a prospective, nonrandomized and uncontrolled study. From March 2001 to December 2003, 475 consecutive patients with hyperhidrosis submitted to ETS were included. A QoL questionnaire was applied at the preoperative day, around the 30th postoperative day, and after the fifth year. RESULTS: After excluding 22 patients who did not answer all the questions, we analyzed 453 patients. Their ages ranged from 11 to 57 years old, with a mean of 25.3 + 7.9 years, including 297 female patients (65.6%). All patients were assessed on three occasions: before surgery, around the 30th postoperative day, and after the fifth postoperative year. The QoL before surgery was considered to be poor or very poor for all patients. The QoL around 30 days after surgery was better in 412 patients (90.9%), the same in 27 patients (6.0%), and worse in 14 patients (3.1%). After 5 years, 409 patients (90.3%) were better, 27 (6.0%) were the same, and 14 (3.1%) were worse. There were no differences between these postoperative times according to the McNemar statistical test. CONCLUSION: The patients had an immediate improvement in QoL after ETS, and this improvement was sustained until the fifth postoperative year. PMID- 22047834 TI - Hypercholesterolemia and oxidative stress inhibit endothelial cell healing after arterial injury. AB - OBJECTIVE: Endothelial cell (EC) migration is essential for arterial healing after angioplasty. Oxidized low-density lipoproteins and oxidative stress decrease EC migration in vitro. The objective of this study was to determine the effect of hypercholesterolemia and oxidative stress on EC healing after an arterial injury. METHODS: C57BL/6 wild-type mice were placed in one of eight groups: chow diet (n = 11), high-cholesterol (HC) diet (n = 11), chow diet plus paraquat (n = 11), HC diet plus paraquat (n = 11), chow diet plus N acetylcysteine (NAC) (n = 11), HC diet plus NAC (n = 11), chow diet plus paraquat and NAC (n = 11), and HC diet plus paraquat and NAC (n = 11). After 2 weeks on the assigned diet with or without NAC, the carotid artery was injured using electrocautery. Animals in the paraquat groups were given 1 mg/kg intraperitoneally to increase oxidative stress. After 120 hours, Evans Blue dye was infused intravenously to stain the area of the artery that remained deendothelialized. This was used to calculate the percentage of re endothelialization. Plasma and tissue samples were analyzed for measures of oxidative stress. RESULTS: The HC diet increased oxidative stress and reduced EC healing compared with a chow diet, with EC covering 26.8% +/- 2.8% and 48.1% +/- 5.2% (P < .001) of the injured area, respectively. Administration of paraquat decreased healing in both chow and HC animals to 18.1% +/- 3.5% (P < .001) and 9.8% +/- 4.6% (P < .001), respectively. Pretreatment with NAC (120 mmol/L in drinking water) for 2 weeks prior to injury, to decrease oxidative stress, improved EC healing to 39.9% +/- 5.7% (P < .001) in hypercholesterolemic mice and to 30.7% +/- 3.6% (P < .001) in the paraquat group. NAC treatment improved healing to 24.6% +/- 3.4% (P < .001) in hypercholesterolemic mice treated with paraquat. CONCLUSION: Re-endothelialization of arterial injuries is reduced in hypercholesterolemic mice and is inversely correlated with oxidative stress. An oral antioxidant decreases oxidative stress and improves EC healing. CLINICAL RELEVANCE: Vascular injury following cardiovascular intervention, including cardiac and peripheral arterial angioplasty and stenting, is associated with inflammation and oxidative stress. Hypercholesterolemia is also associated with increased oxidative stress. Oxidative stress, regardless of the source, induces cellular dysfunction in endothelial and smooth muscle cells that reduce healing after arterial injury. Decreasing oxidative stress with an exogenously administered antioxidant can improve endothelial cell healing, and this is important to control intimal hyperplasia and reduce the thrombogenicity of the vessel. PMID- 22047835 TI - [Ranking 2010 in production and research productivity in Spanish public universities]. AB - The creation of the European Higher Education Area has brought the relevance of the scientific quality assessment in higher education. The result of this interest is a growing interest in the development of rankings of universities, both nationally and internationally. To continue the line started two years ago, the goal of this research is to update the ranking of research productivity in Spanish public universities with the data of 2010. We follow the same methodology to data from 2008 and 2009; although this year it includes measures of total production. The same indicators to evaluate research in 2009: journals articles indexed in the JCR, research periods, research + development projects, doctoral dissertations, grants for training university teachers, Doctoral Programs with Quality Mention and patents. From the results obtained show that universities with higher production were Complutense de Madrid, Barcelona and Granada. The most productive were the Pompeu Fabra University, the Pablo de Olavide, and the Autonoma de Barcelona. PMID- 22047836 TI - [Effectiveness of two smoking prevention programs according to type of applicator]. AB - Although research on the prevention of drug use has shown that the effectiveness of programs depends partly on who applies them, the results of studies designed to clarify this issue are contradictory. This study compared the effects on smoking, in the short and medium term, of the implementation of two school-based prevention programs, depending on the type of applicator. The sample was made up of 200 seventh-grade students distributed among five experimental conditions: four of intervention, in which the programs were implemented by teachers from the school or by external psychologists, and one of control. The results show that teachers applying the Barbacana program and psychologists applying the Construyendo Salud (Building Health) program succeeded in reducing the incidence of cigarette smoking (BR-teachers 15%; C.S-psychologists 5%) and strengthening attitudes against smoking. An interaction effect between type of program and type of applicators was clearly observed. PMID- 22047837 TI - Influence of the friends' network in drug use and violent behaviour among young people in the nightlife recreational context. AB - Party networks of young people are important for socialization, but can also influence their involvement in risk behaviours. We explored the individual centred networks (7.360 friends) of 1.363 recreational nightlife users in 9 European cities in 2006, through 22 friend characteristics. As expected, deviant networks are related to violence, smoking, illegal drug use and drunkenness. However, socializing and helping networks are also associated with fighting, smoking, use of illegal drugs--except for cannabis--and getting drunk. Not having a deviant network and not having a helping/socializing network can be protective against smoking, violence and illegal drug use, as well as protecting ex-users from relapse. Closeness to friends is also a network protective factor. A possible reason why socializing networks are related to fighting, illegal drugs and drunkenness is that these behaviours are somehow desired, adaptive and prosocial in recreational contexts. PMID- 22047838 TI - [Do adolescents who use stimulants have a different personality?]. AB - Stimulant consumption is especially important in our context because its use has greatly increased in recent years. The aim of the present study is to analyze the differences between stimulant users and nonusers (under 18 years old) in personality characteristics assessed with the MACI. The sample comprises 398 youths between 14 and 17 years old who were selected through random sampling in their homes or in recreational night spots. Results show important differences in personality features between stimulant users and nonusers. Stimulant users are characterized by having unruly, forceful, oppositional and borderline-tendency personality prototypes. PMID- 22047839 TI - [Effectiveness of treatments for social phobia in an applied field]. AB - Social phobia is one of the most common disorders and one that requires the most attention from psychological clinics. The aim of this article was to study the effectiveness of psychological treatments in a University Psychological Clinic. Seventy-one social phobia patients requested psychological assistance. The average number of assessment sessions was 3.8 and the average number of treatment sessions was 16.1. Therapeutic success reached 64.2%, withdrawal percentage was 11.3%, and drop-out percentage was 24.5%. The effect size (Cohen's d) achieved in the Social Avoidance and Distress Scale (SAD) and Fear of Negative Evaluation Scale (FNE) were 1.96 and 1.78, respectively. Comparing these results with efficacy research (particularly meta-analysis), it has been shown that the treatment effectiveness achieved is very similar. It is concluded that cognitive behavioural treatments for social phobia can be transferred from research settings to clinical practice. PMID- 22047840 TI - [Therapeutic tasks: what kind of help is sought in psychotherapeutic sessions?]. AB - One of the main conditions for a good psychotherapeutic alliance is the agreement on therapeutic tasks and goals. This article explores the kind of help that clients expect from therapeutic sessions. By means of a written questionnaire, the clients of a private psychotherapy center, prior to the sessions, expressed their priorities regarding the work to be carried out in them. The assessment of 873 questionnaires showed that clients prefer to participate in therapeutic work that helps them plan actions, understand what is happening, and assess possibilities for change. Also important are therapeutic tasks that help clients evaluate their own actions, both past and planned. The importance that clients attach to different kinds of help varies above all according to how near they feel to resolving their problems. Nine different kinds of psychotherapeutic tasks are identified, which cover the possible requests a client can make of his/her therapist. This article discusses the clinical application of this model as a basis for planning and classifying psychotherapeutic interventions. PMID- 22047841 TI - [Why are psychological treatments prolonged? Predictors of a longer duration of treatment and analysis of the differences between long- and short-term cases]. AB - The purpose of this study was to identify variables that may explain a longer psychological treatment and to analyze differences between short- and long-term cases. Data from 419 patients of the University Clinic of Psychology at the Complutense University of Madrid were analyzed. Number of intervention techniques, comorbidity, previous treatments, and a primary diagnosis of mood disorder or eating disorder were the factors that explained longer treatment duration. Significant differences were observed between short- and long-term cases in number of intervention techniques, number of therapeutic objectives, and also in some clinical variables (diagnostic group, comorbidity, previous treatment) and demographics (age and educational level). Results are discussed and some lines of intervention and/ or reflection are proposed. PMID- 22047842 TI - [Assessment of emotional reactivity to food images in bulimia nervosa]. AB - The aim of the study was to assess the influence on reactivity to food images of the following variables: craving-trait, positive or negative mood state, and food restriction. Emotional modulation of the defense startle reflex (RMS) was assessed in 26 women at risk of suffering from bulimia nervosa; they were assigned one of to two groups: high craving-trait and low craving-trait. Before the test, positive or negative mood and restriction vs. non-restriction states were induced in each of the groups. Skin conductance response (SCR) and electromyogram activity from the orbiculari oculi region were recorded after the auditory stimuli; questionnaires such as Food Craving Trait Questionnaire (FCQ-T) and the Self-assessment Manikin (SAM) were used. Results showed that negative affect produced a negative valence of food images, more arousal, and more loss of control, as well as higher SCRs. Subjects with low FCQ-T levels reduced their RMS to food images as a consequence of experiencing positive emotions; when emotions were negative, their RMS increased. PMID- 22047843 TI - The control dilemma in eating behavior: influence of temptation cues in restrained versus unrestrained eaters. AB - The present research explored the effects of pre-exposure to temptation primes and dieting primes on food intake, goal accessibility and explicit automatic evaluations of food-enjoyment and dieting goals among restrained and unrestrained eaters. Participants (n= 166) were randomly assigned to three conditions: food cue, dieting, or control, in which they were exposed to incidental presentation of gourmet, fashion or geographic magazines, respectively. Words related to the goals of dieting and/or food- enjoyment were presented in a computer decision task following the incidental presentation of gourmet, dieting, and geographic magazine photographs. The computer task and the presentation of food were counterbalanced. Participants' food intake was assessed in a taste-rating task. Restrained eaters ate more than did unrestrained eaters across the three conditions. Restrained eaters who were exposed to food cues ate more than did restrained eaters in the control condition and they evaluated the goal of dieting more negatively compared to restrained eaters in the other two conditions. These findings were inconsistent with 'Counteractive Self-Control Theory' but consistent with previous studies on the effects of food-cue exposure in restrained eaters. PMID- 22047844 TI - [Cardiovascular health in women: the role of anger and its expression]. AB - The relationships between anger expression (in, out, and control) and cardiovascular health (emotional distress, cardiovascular symptoms reported, and preventive health behaviors) were analyzed in 327 women (range 17-60 years). The same criteria (N= 218), as well as blood pressure (BP) registered in medical checkups (N= 90) were recorded one year later. Four groups according to anger-in and anger-control scores, going from the most hostile (high anger-in and low anger-control) to the least hostile (low anger-in and high anger-control) were considered. The results indicated that the most hostile group, with the least adaptive anger expression, presented worst cardiovascular health than the other three groups, at both temporal moments. Furthermore, the presence of women with pathological BP levels was higher in the groups of high anger-in. These data ratify the role of anger expression, especially its repression (anger-in) and the lack of adequate canalization or control in women's cardiovascular health from a prospective design. Appropriate management of anger feelings and the practice of preventive health behaviors can protect women from cardiovascular problems. PMID- 22047845 TI - [Improving comprehension and communication of risks about health]. AB - Many patients have severe difficulties grasping several numerical concepts that are related to their health, such as, for instance, the risk of suffering various diseases. Visual aids have been proposed as a promising method for enhancing risk communication and comprehension. In medical practice, however, not all patients benefit from visual aids. In a study conducted on a probabilistic, representative national sample in the United States, we identified a group of patients for whom visual aids are most useful: Those who have low numeracy but high graphical literacy skills. These patients have high scores in three abilities involved in graph comprehension: (1) the ability to read the data, (2) the ability to read the relations between the data, and (3) the ability to read beyond the data. Our results can have important implications for medical practice and for risk communication about health. PMID- 22047846 TI - [Accuracy of diagnosis of depression in patients with Type 1 diabetes mellitus]. AB - This study assesses the clinical accuracy of physicians (Specialists in Endocrinology and Nutrition: SEN) to make the diagnosis of depression in patients with Type 1 diabetes mellitus (DM1). This study involved 11 SEN physicians, and 153 patients with DM1. The diagnosis of depression was performed using the SCID-1 structured interview and clinical assessment. From the initial sample, 50 patients were randomly selected (imposing the condition that it was included 25 patients with depression and 25 without depression). The results show that clinicians performed a higher percentage of negative diagnoses (patients without depression) than positive ones (patients with depression). A significant percentage of patients with depression were not diagnosed (25%). It therefore seems necessary to provide adequate clinical protocols to evaluate the presence of this disorder in DM1, as well as continuing research into the diagnostic process for clinical decision making. PMID- 22047847 TI - [Dispositional optimism, pessimism and realism in technological potential entrepreneurs]. AB - Optimism has been classically considered a key trait in entrepreneurs' personality but it has been studied from a psychological point of view only in recent years. The main aim of this research is to study the relationship between dispositional optimism, pessimism and realism as a function of the tendency to create technology-based businesses. A sample of undergraduate students (n= 205) filled in an electronic questionnaire containing the Life Orientation Test Revised after they were classified as potential technological entrepreneurs, potential general entrepreneurs and non-potential entrepreneurs. Our results show that technology-based entrepreneurs are more optimistic than non-potential entrepreneurs, whereas there were no statistical differences in pessimism and realism. The results are interpreted theoretically to define the potential entrepreneur and, from an applied perspective, to design training programmes to support future technological entrepreneurs. PMID- 22047848 TI - [Antecedents and consequences of workplace bullying: a longitudinal analysis with a structural equation model]. AB - Most studies focusing on the antecedents and consequences of workplace bullying have used a cross-sectional design, which impedes determining the causality of the relationships. In the present work, we analyzed, by means of structural equation models, the relationship between workplace bullying and some variables that are considered antecedents (interpersonal conflicts, role ambiguity, role conflict, and workplace social support) or consequences (health complaints and inclination to absenteeism from work) of this phenomenon. Multicenter study with two phases. The sample consisted of 696 employees from 66 centers. Workplace bullying was assessed by means of the "Mobbing-UNIPSICO" questionnaire, and the other variables with frequency scales. The cross-sectional models indicated a significant association between role conflict, workplace social support, and workplace bullying in both study periods. Concerning the longitudinal relationships, only workplace social support was a significant predictor of workplace bullying, which, in turn, was a cross-sectional and longitudinal predictor of workers' health complaints. Our results show the mediating effect of workplace bullying between certain work conditions and health complaints, and it is recommendable to replicate these findings in a multi-occupational sample. PMID- 22047849 TI - [Prevalence and differentiating aspects related to gender with regard to the bullying phenomenon in poor countries]. AB - There is a large body of scientific knowledge about school violence and bullying in Europe and some other regions of the so-called developed world. However, improvement is scarce in poor and developing regions, as in the case of Latin America and, in particular, Nicaragua. The goal of this work was to determine the prevalence of the bullying phenomenon in Nicaraguan primary schools, to analyze the eventual relationships between the different forms of violence used by the students and to explore, in relation to these aspects, the similarities and differences between boys and girls. For this purpose, we surveyed 3042 pupils of primary school (50.3% girls) using the "Cuestionario sobre Convivencia, Violencia y Experiencias de Riesgo" (COVER, in English, Questionnaire about Living Together, Violence and Risk Experiences). We found that the level of involvement in bullying is significantly higher than in developed countries, that boys are more involved than girls in verbal, physical and psychological bullying, and that there are no differences with regard to social exclusion. The results are discussed, comparing them with studies conducted in different countries but with similar methodologies. PMID- 22047850 TI - [Adoptive parents' satisfaction with the adoption experience and with its impact on family life]. AB - In this study, we discuss the relevance of adoptive families' satisfaction in the assessment of adoption processes. The effects of adoption on a sample group of 272 adoptive families are analyzed. Most families show high levels of satisfaction as to: their decision to adopt, the features of their adopted children and how adoption has affected them as individuals and as a family. Statistical analyses show that these families can have different satisfaction levels depending on certain features of the adoptees, of the adoptive families or of their educational style. Life satisfaction of the adoptees is also related to how their adoptive parents evaluate the adoption. PMID- 22047851 TI - [Description of the Parental Alienation Syndrome in a forensic sample]. AB - The aim of this paper was to assess the presence of the criteria for Parental Alienation Syndrome (PAS) in a sample of families in the process of divorce. Thirty nine records obtained from family cases evaluated by a forensic psychology service were analyzed. A checklist of criteria was made using the description of PAS, these criteria served to confirm their presence by assessing the three actors in the dynamics of the PAS: both parents and the child. The presence of these criteria was analyzed comparing the groups with and without interruption in the contacts. The results showed a strong correlation between the criteria defining the PAS. The presence of these criteria was much higher in the group with interrupted contacts versus the group with uninterrupted ones. However, taking into account the disorders that were computed in visiting parents, there were no differences between both groups. These results seem to confirm the presence of the criteria of PAS in families that are in a process of marriage breakdown with disruptions or conflicts in the visitation rights. PMID- 22047852 TI - [Child Protection Services caseworkers' assessment of child maltreatment severity]. AB - The goals of this research were to explore accuracy and consistency in the assessment of child maltreatment severity in Spanish Child Protection Services (CPS) and the influence of caseworker's service, gender, professional discipline, degree of dedication to CPS, and years of experience on the accuracy of the assessment of maltreatment severity. Two studies were conducted with 515 and 168 caseworkers from two Spanish CPSs. Case vignettes were used. Caseworkers of both groups were asked to rate severity of the assigned case vignettes, applying the criteria used in their daily work. Caseworkers in both studies obtained low levels of accurate ratings. None of the total vignettes obtained a percentage higher than 80% of inter-rater agreement. No significant relationships were found between accuracy of ratings and caseworkers' service, gender, professional discipline, degree of dedication to CPS, and years of experience. PMID- 22047853 TI - Diagnostic value of the Dominic Interactive Assessment with children exposed to intimate partner violence. AB - This article reports on the diagnostic validity of the Dominic Interactive Assessment (DIA) in a sample of Spanish children exposed to intimate partner violence (IPV). The study participants included 55 children aged between 6 and 11 years whose mothers visited an IPV counselling centre. Psychopathology and functional impairment were used as the main criteria for assessing predictive and discriminative accuracy, as well as incremental validity, of DIA. The results indicate that DIA permits obtaining useful information from children. This information improves the prediction and validity of the process of clinical assessment of children exposed to IPV. Children's self-reports could prove effective in identifying cases in this high-risk population when developmentally adequate instruments and functional criteria are used. PMID- 22047854 TI - [Parenting practices and internalizing and externalizing problems in Spanish adolescents]. AB - The goal of this study was to analyze the relationship between parenting practices and internalizing and externalizing problems presented by a group of adolescents according to their gender. Four hundred and sixty-nine secondary school students (aged between 12 and 18) participated in this study. The adolescents presented differences in perception of the educational practices of both parents as a function of their gender. Negative parenting practices were positively related to adolescents' internalizing and externalizing problems, whereas positive practices were negatively related to externalizing problems. Moreover, differences between boys and girls were found in predictor variables of problems, and the predictive power of the variables was higher for externalizing problems. PMID- 22047855 TI - [Psychopathic personality as a distinctive indicator of severity and persistence for child and youth conduct problems]. AB - Conduct problems are among the most discussed behavioral problems during childhood and adolescence. Given their heterogeneity, in recent years, researchers on this topic have called for delineation of early-onset conduct problems on the basis of affective, interpersonal and behavioral traits that resemble adult psychopathy. The present study aims to analyze, from both a cross sectional and longitudinal perspective, whether early psychopathic traits allow identification of a group of individuals defined by severe and persistent behavioral problems. To achieve this goal, data from a sample of 192 children (aged 6 to 11) were analyzed; from this sample, 133 children were followed-up in a new data collection that took place three years later. From the data obtained with the mCPS and CBCL (parents), and APSD and TRF (teachers), we observed that children who showed early psychopathic traits, also showed greater frequency, severity and persistence of conduct problems. These results suggest the need to take into account the role of psychopathic traits (particularly, affective and interpersonal) as risk factors to delimit the most serious and persistent patterns of externalizing behavior. PMID- 22047856 TI - Sex differences in oppositional defiant disorder. AB - The goal was to analyze the sex differences in symptoms, comorbidity and functional impairment in outpatient children with Oppositional Defiant Disorder (ODD). A sample of 343 children, aged 8 to 17 years and diagnosed with ODD, were assessed with a semi-structured diagnostic interview and dimensional measures of psychopathology and functional impairment. Boys with ODD more frequently displayed the symptoms "deliberately annoys" and "blames others", presented comorbid ADHD, and had greater functional impairment in school and community contexts; girls presented higher comorbidity with internalizing symptomatology (anxiety, depression and somatic complaints). Given that some clinical differences are apparent in ODD between boys and girls, it is necessary to consider the sex of the patient in order to identify and treat this disorder efficiently and effectively in boys and in girls. PMID- 22047857 TI - [Comparison of two self-regulated and strategic instructional programs for improving writing competence]. AB - This study compared the efficacy of two versions of an instructional program aimed at developing strategic and self-regulated writing competence. In the full version, strategy instruction, students were taught strategies for producing effective text, using a combination of direct (explicit, declarative, metacognitive knowledge) instruction, teacher modeling, and collaborative and individual practice. In a modeling-only version, direct instruction was omitted. 72 Spanish 6th grade students were taught in one of three groups: Full Strategy Instruction (N=24); Modeling only (N=25), and a normal curriculum (no strategy instruction) control (N=23). Pre and posttest measures of written texts, self efficacy and self-knowledge of writing were taken. Pre and posttest scores on writing ability tests indicated similar improvement in both intervention groups, relative to control, in both holistic measures of text quality and in counts of text features associated with mature, reader-focused composition. We found no differences between intervention groups. These findings suggest that modeling and student practice alone are sufficient to develop effective writing strategies in typically-developing 6th grade students. PMID- 22047858 TI - [English as a foreign language (EFL) homework diaries: evaluating gains and constraints for self-regulated learning and achievement]. AB - Although homework completion is said to be rather important to achievement, nowadays there is a growing concern of educators about the increasing number of students who do not engage properly on doing the homework tasks and the subsequent impact on school failure rates. Focusing on English as a Foreign Language (EFL) and using a sample of 591 Portuguese fifth and sixth graders, the present study analyses the role played by a number of homework variables on students' achievement (proximal and distal), and their mediating role on the use of self-regulated learning strategies and perceived self-efficacy in the domain. Data confirm the indirect effect of homework on school achievement, by means of the referred cognitive and motivational variables (use of self-regulated learning strategies and self-efficacy). These findings are further discussed in order to highlight the significant role homework completion can play on fighting school failure. PMID- 22047859 TI - [Language and executive functioning skills of students with attention deficit/hyperactivity disorder (ADHD), and in reading comprehension difficulties (RCD)]. AB - The aim of this work was to study the specificity of deficits in linguistic and executive functioning of students with ADHD and with RCD and to determine the profile of deficits in the comorbid group (ADHD+RCD). Participants in the study were 84 students, ages 12-16 years divided into four groups with an equal number of subjects (N= 21): ADHD, RCD, ADHD+RCD and comparison group (without ADHD and without RCD). We measured vocabulary, oral comprehension, lexical access, verbal and visual working memory, inhibition and attention. The results show that the ADHD+RCD group presents the most important linguistic deficits, followed by the RCD group. On the other hand, the three clinical groups (ADHD, RCD and ADHD+RCD) display greater performance problems in working memory than the comparison group, whereas the two groups with ADHD had more problems in attention and inhibition. These results suggest the dissociation of linguistic and executive deficits that affect the RCD group and ADHD group to a greater extent, respectively. Lastly, the comorbid group showed deficits both in language and in executive skills. We discuss the implications of these findings for designing interventions. PMID- 22047860 TI - Cognitive abilities, sociocultural background and academic achievement. AB - The influence of students' sociocultural background on academic achievement is a well established fact. Research also points out that sociocultural background is related to students' cognitive abilities and these have an effect on their academic achievement. However, the mediator role of cognitive abilities on the relationship between sociocultural background and academic achievement is less well known. A structural equation model that represents these relationships was tested in a sample (N= 728) of Portuguese junior high school students. Multigroup analysis of the model showed the importance of the cognitive ability mediation effect between sociocultural background and academic achievement in the 7th and 9th grades, but not in the 8th grade. This difference may be the result of the academic transition experienced in the 7th and 9th grades in the Portuguese educational system, which requires parents' higher involvement in school. PMID- 22047861 TI - [PISA and the assessment triangle]. AB - PISA is a well-known and high profile Program for International Student Assessment with 4 editions since 2000. This study aims to examine the validity of PISA proficiency estimates, working with the framework provided by the assessment triangle. We pay explicit attention to how PISA proceeds as far as the three elements of the assessment triangle are concerned: cognition, observation, and interpretation. Results reveal not only the psychometrically sound proficiency estimates of PISA and the high standards reached, but also that there is room for improvement; for instance, cognitive diagnostic models could contribute both to test design and data analysis. PMID- 22047862 TI - [Alexithymia and experimentally induced emotion recognition in people with somatizations]. AB - This study is part of an investigation aimed at assessing the cognitive-emotional process of emotional recognition in somatizing patients. The specific objective was to verify whether there were differences in the self-assessment of emotional reaction among patients with somatization and non-clinical controls. To obtain the self-assessment of their emotional reaction in the affective dimensions of valence and activation in clinical and control participants, we resorted to a procedure that minimizes the use of verbal skills and comprehension. Participants were 119 people, 47 patients and 72 non-clinical participants. The prevalence of alexithymia in the clinical group was 42.55%, whereas in non-clinical controls, it was 30.55%. Results showed the existence of a deficit in the clinical group's self-assessment of activation in response to the corresponding images with high levels of the affective dimension of activation and high valence images, associated with the clinical condition but not with alexithymia. Alexithymia has a modulatory effect on the clinical participants' and controls' evaluation of the valence of the unpleasant images or of low valence pictures. PMID- 22047863 TI - [Influence of clinical status in the relationship between alexithymia and emotional recognition: a dimensional study]. AB - The results of this study are part of an investigation to determine whether the cognitive-emotional process of emotional recognition is deficient as a function of the clinical condition and alexithymia in subjects with somatization. This investigation applied the self-assessment of emotion and used a procedure that minimizes the use of verbal skills and verbal comprehension. The specific goal of this study was to verify whether there were differences in the covariation between alexithymia and self-evaluation of the emotional reaction in clinical and nonclinical subjects. The results of this study highlight the significant differences between clinical and control subjects. There were inverse significant correlations with the affective valence in clinical subjects, whereas in the ratings of the TAS-20 in control subjects, there were direct correlations with activation. In the conclusions, we discuss whether the variability of the results of previous research of the relationship between alexithymia and emotional recognition is a characteristic feature of this relationship or an effect of the different sampling and procedures utilized. PMID- 22047864 TI - [Full naming with bi-dimensional abstract stimuli in six-year-old children]. AB - The aim of this study was to evaluate a procedure to reveal the emergence of full naming in typically developing children. In Experiment 1, five 6-year-old children (a) learned tacts of pictures and the emergence of the selection of these pictures upon hearing their names was tested; and (b) the selection of other pictures was taught and the emergence of the tacts was tested. All children showed the emergence of picture selection and 3 children showed the emergence of the tacts. In Experiment 2a, the children's correct repetition of the names of 3 pictures was verified first, then the experimenter presented the pictures with their names without requiring any behavior other than attending. Finally, the emergence of picture selection and the tacts was tested. Experiment 2b replicated Experiment 2a with words that were easier to pronounce. Picture selection and the tacts emerged; this performance documented full naming for the first time with typically developing children. These procedures can be used to induce naming capacity in children who lack it; hence, they can be applied to teach children with learning delays. PMID- 22047865 TI - [General cognitive functioning and psycholinguistic abilities in children with Smith-Magenis Syndrome]. AB - This study is a neuropsycholinguistic research of a rare genetic syndrome with microdeletion that co-occurs with intellectual disabilities and relatively good language abilities, the Smith-Magenis Syndrome (SMS). Nevertheless, there are no cognitive and psycholinguistic profile analyses performed with Spanish population. In this sense, we characterized the cognitive and psycholinguistic profile of a sample with 9 participants with SMS (7 to 11 years of age). The cognitive and psychological profile was assessed with diverse standardized tests: Wechsler Intelligence Scale for Children - IV version, Illinois Test of Psycholinguistic Abilities and Peabody Picture Vocabulary Test. Results suggest a specific cognitive and psychological profile characterized by a low IQ and relative good abilities in integrating information, whereas attention problems and hyperactive behaviors were displayed when interacting with the child during the assessment. This work is the first evidence of the cognitive and psycholinguistic profile characterization in patients with SMS in Spain, and will help to guide a more accurate diagnosis and differential intervention in rare genetic diseases with similar cognitive and psycholinguistic profiles. PMID- 22047866 TI - [Neuropsychological impairment in Parkinson's disease without dementia]. AB - Cognitive dysfunction in Parkinson's Disease (PD) has been consistently reported, but little is known about cognitive impairment in PD patients without dementia, and its association with clinical characteristics, neuropsychiatric disturbance and functional activities. Therefore, we evaluated 52 non-demented PD patients, 22 of them with mild cognitive impairment (PD-MCI) who were matched with 52 healthy controls. Our results confirm the existence of dysfunction in information processing speed, executive function, verbal memory and visuo-perceptual processing in PD. On the other hand, PD-MCI was associated with advanced age at the onset of PD, more neuropsychiatric symptoms, caregiver stress and functional problems. The study supports the hypothesis that specific neuropsychological impairments may act as modulators of functional impairment in PD, for instance slowness of information processing. PMID- 22047867 TI - [Artificial neural networks in Neurosciences]. AB - This article shows that artificial neural networks are used for confirming the relationships between physiological and cognitive changes. Specifically, we explore the influence of a decrease of neurotransmitters on the behaviour of old people in recognition tasks. This artificial neural network recognizes learned patterns. When we change the threshold of activation in some units, the artificial neural network simulates the experimental results of old people in recognition tasks. However, the main contributions of this paper are the design of an artificial neural network and its operation inspired by the nervous system and the way the inputs are coded and the process of orthogonalization of patterns. PMID- 22047868 TI - [Psychological variables in the control of brain-computer interfaces]. AB - BCI (Brain-Computer Interface) is a system that allows interaction between the human brain and a computer. It is based on analyzing electroencephalographic signals (EEG) and processing them to generate control commands. The study analyzed the possible influence of psychological variables, such as the imaginative kinesthetic capacity and anxiety, in relation to performance in a BCI. All participants (4 male and 19 female students) completed the questionnaires and carried out a session of BCI to control their EEG signals in a virtual setting of a car along a straight road. The group was divided into two subgroups according to their EEG signals or differential responses obtained in the left-right discrimination. Study results showed no significant differences in cognitive variables of imagination or in anxiety. By comparing the degree of participants' BCI control, a new quantitative parameter for comparing performances and making decisions in signal processing was found. The findings, the ongoing research process to refine the control of a BCI, and the interaction of psychological and computer procedures are discussed. PMID- 22047869 TI - Sexual orientation and spatial memory. AB - The present study aimed at determining the influence of sexual orientation in human spatial learning and memory. Participants performed the Boxes Room, a virtual reality version of the Holeboard. In Experiment I, a reference memory task, the position of the hidden rewards remained constant during the whole experiment. In Experiment II, a working memory task, the position of rewards changed between blocks. Each block consisted of two trials: One trial for acquisition and another for retrieval. The results of Experiment I showed that heterosexual men performed better than homosexual men and heterosexual women. They found the rewarded boxes faster. Moreover, homosexual participants committed more errors than heterosexuals. Experiment II showed that working memory abilities are the same in groups of different sexual orientation. These results suggest that sexual orientation is related to spatial navigation abilities, but mostly in men, and limited to reference memory, which depends more on the function of the hippocampal system. PMID- 22047870 TI - Predictive learning in nutrient-based flavor conditioning. AB - This paper presents two experiments on nutrient-based flavor conditioning with rats as subjects and sucrose as the unconditioned stimulus (US). Experiment 1 was aimed at establishing an optimal control for conditioning, comparing simultaneous and serial presentations of a flavor and the US. The results showed that simultaneous, but not serial training, produced conditioning. Experiment 2 was designed to obtain evidence of summation as an index of both conditioned inhibition and predictive learning. Group Simultaneous received Pavlovian conditioned inhibition training during which flavor A was simultaneously paired with sucrose on excitatory trials (A+), and forming an unreinforced compound with flavor B on inhibitory trials (AB-). An independent excitor for the summation test was also trained by simultaneous pairings with sucrose (C+). In the control group (Blocked), the AB- trials were presented forming a block at the beginning of training to avoid a negative contingency-relationship with sucrose, and flavor A received serial rather than simultaneous pairing with sucrose (A --> +). On the summation test, only in group Simultaneous was consumption of the CB compound lower than that of flavor C alone, suggesting that, during training, flavor A activated an expectancy of the US occurrence. PMID- 22047871 TI - [Agustin Moreno: scientific psychology and women's legal responsibility in Spain]. AB - Agustin Moreno Rodriguez (1886-1967) studied Medicine and Natural Sciences at the Central University of Spain, in Madrid. He was a student of Dr. Luis Simarro, the University's professor of Experimental Psychology and of Tomas Maestre, the University's professor of Medical Law, Toxicology and Psychiatry. In 1910, he published the text The woman's civil and penal responsibility during the menstrual period. In this work, he approaches the question of the legal responsibility of women, based on the principle of excitation/reaction of Claude Bernard and on his personal version of the concept of iteration elaborated by Luis Simarro. Dr. Moreno also defends the thesis that menstruation adds some uniqueness to the function of the feminine psyche and, therefore, modifies the responsibility of a woman's actions. We also comment on the predominant approach to the mind of women in the Spanish scientific psychology of that time and the reaction of the Spanish feminist intellectuals. PMID- 22047872 TI - [Factor structure of the Spanish adaptation of Tarrant's Group Identification Scale]. AB - In this study, the factor structure of the Spanish version of Tarrant's Group Identification Scale is analyzed. This scale is based on the social identity theory and measures cognitive, evaluative, and affective aspects of group identification. Although this scale has been considered unidimensionally with adolescents, it is based on previous group identification scales considered multidimensionally. From confirmatory analysis, some factor models were tested in two independent samples of adolescents: Spanish (N= 1,795) and Mexican (N= 1,494). The three-factor model (self-categorization, group evaluation, and commitment to the group) produced the best fit in both samples. Results are compatible with the multidimensional structure hypothesis of group identification. PMID- 22047873 TI - [Spanish validation of an emotion-eliciting set of films]. AB - One of the main difficulties in the study of emotion is the induction of a real emotional response by means of artificial techniques. The aim of the current study is to validate the Spanish version of a set of films with the capacity to induce emotions (PIE) under laboratory conditions and to analyze its capacity to provoke differentiated basic emotions. A sample of 127 subjects took part in the study; 57 excerpts of Spanish-dubbed films with capacity in previous studies to induce 7 emotions: anger, fear, sadness, disgust, amusement, tenderness, and neutral emotion were used. Subjective emotional response was measured using the Self-Assessment Manikins and the Discrete Emotions Questionnaire. Films included showed a good capacity to induce positive and negative affects, high levels of emotional activation and variations in the perception of emotional control. They induced basic emotions of amusement and fear in a differentiated way. However, sadness and disgust could not be significantly differentiated from anger; or anger and tenderness from sadness. The PIE could be a useful tool for the experimental research of emotions in Spanish populations. PMID- 22047874 TI - [Psychometric quality supporting the Spanish adaptation of the Behavioral Regulation in Sport Questionnaire]. AB - The goal of this study is to present the Spanish adaptation of the Behavioral Regulation in Sport Questionnaire made up of 24 items that measure the 6 behavioral regulation factors expected by the self-determination theory developed by Deci and Ryan. Supporting evidence of conceptual equivalence and quality of the cultural and linguistic adaptation derive from the conciliation of different terms (experts and target population). Cognitive interviews and the fact that 94% of respondents provided complete answers and without aberrant response patterns support the feasibility of the questionnaire. A model of six correlated factors provided the best fit to the data in the confirmatory factor analysis, and 5 out of 6 subscales have acceptable internal consistency coefficients. The scores of the introjected, identified, and integrated regulation show more variability than the other ones. As expected, the 6 subscales show a graduation of direct correlation with the subjective vitality measure and an inverse correlation with competitive anxiety. The accumulation of evidence leads to the conclusion that the Spanish version is valid for use in sport psychology research. PMID- 22047875 TI - [Adaptation to Spanish of the "Scale of perceived social support specific to the disease" of Revenson et al., 1991]. AB - This study aims to analyze the psychometric properties of the Spanish version of the Scale of Perceived Social Support Specific to the Illness of Revenson et al. 1991. A sample of 202 patients with chronic conditions was used. After making several factor analysis of the scale on all four versions (partner, family, friends and doctors), it was found a structure formed by two factors involving positive social support and not functional or problematic social support. The results obtained with Cronbach's alpha show that all scales have acceptable and adequate internal consistency. In this sense, this scale may be appropriate to identify properly perceived social support for chronic patients on the four sources of support studied. PMID- 22047876 TI - eCAT-Listening: design and psychometric properties of a computerized adaptive test on English Listening. AB - In this study, eCAT-Listening, a new computerized adaptive test for the evaluation of English Listening, is described. Item bank development, anchor design for data collection, and the study of the psychometric properties of the item bank and the adaptive test are described. The calibration sample comprised 1.576 participants. Good psychometric guarantees: the bank is unidimensional, the items are satisfactorily fitted to the 3-parameter logistic model, and an accurate estimation of the trait level is obtained. As validity evidence, a high correlation was obtained between the estimated trait level and a latent factor made up of the diverse criteria selected. The analysis of the trait level estimation by means of a simulation led us to fix the test length at 20 items, with a maximum exposure rate of .40. PMID- 22047877 TI - [The Reading Literacy test for Secondary Education (CompLEC)]. AB - A new test to evaluate reading literacy, the Test of Reading Literacy for Secondary Education (CompLEC) is presented. CompLEC is based on the PISA assessment framework and new definitions of reading literacy. The test, easy to apply and score, assesses the level of reading literacy of children between 11 and 14 years of age in several reading situations (i.e., public, educational, personal and occupational) and with different types of texts (i.e., continuous and non-continuous). The scale has been standardized with a sample of 1,854 students from five different Spanish regions. Empirical results show that CompLEC is a homogeneous, reliable and valid instrument. PMID- 22047878 TI - [Utility of a statistical model of cognitive styles in attention deficit hyperactivity disorder]. AB - The purpose of this study was to determine the best statistical model of cognitive styles, based on the MFFT-20, CEFT and Stroop tests to predict attention deficit hyperactivity disorder (ADHD), analyzing the validity of the model for the diagnosis of the disease. We studied 100 ADHD cases (DSM-IV criteria) and 100 controls, age ranging between 7 and 11 years. Controls were randomly recruited and matched in age, gender and sociodemographic area with ADHD cases. On average, ADHD cases showed more impulsiveness (d: 1.28), less cognitive flexibility (d: 0.91) and more field dependence (d: 1.62) than controls. The logistic regression model that predicts ADHD best is made up of age, CEFT, MFFT 20 and Stroop tests and the formula derived from the model shows 85% sensitivity and 85% specificity for ADHD, regarding the DSM-IV criteria as the standard. The statistical model of cognitive styles presents valid indicators to diagnose ADHD, contributing to an increase in the objectivity of its analysis. PMID- 22047879 TI - [Psychometric properties of the Interpersonal Reactivity Index in Spanish child and adolescent population]. AB - This article analyses the dimensions of the Interpersonal Reactivity Index (IRI; Davis, 1980). The sample comprised 721 Spanish participants between 9 and 16 years old. Diverse exploratory factor analyses were conducted as the basis for the final confirmatory factor analysis, through self-report. The results supported a structure with 5 first-order main factors (Intellectual empathy, Positive emotional empathy, Disorganized emotional empathy, Virtual empathy, and Impassiveness), where the two first factors are nested in a second-order dimension: "Considerate Social Style". The psychometric characteristics of the instrument were adequate. The proposed model is a new alternative to conceptualize the factor structure of empathy. PMID- 22047880 TI - Structural invariance of multiple intelligences, based on the level of execution. AB - The independence of multiple intelligences (MI) of Gardner's theory has been debated since its conception. This article examines whether the one- factor structure of the MI theory tested in previous studies is invariant for low and high ability students. Two hundred ninety-four children (aged 5 to 7) participated in this study. A set of Gardner's Multiple Intelligence assessment tasks based on the Spectrum Project was used. To analyze the invariance of a general dimension of intelligence, the different models of behaviours were studied in samples of participants with different performance on the Spectrum Project tasks with Multi-Group Confirmatory Factor Analysis (MGCFA). Results suggest an absence of structural invariance in Gardner's tasks. Exploratory analyses suggest a three-factor structure for individuals with higher performance levels and a two-factor structure for individuals with lower performance levels. PMID- 22047881 TI - [Assessment of individual differences in faking]. AB - In recent years, change scores obtained under neutral conditions and under faking inducing conditions have become one of the main alternatives for operationalizing faking. A pending issue regarding these measures is the relevance of individual differences under similar conditions of pressure. This study proposes a simple approach based on the classic test theory that allows the issue to be rigorously assessed. The approach, from which three indices are derived, is based on a pre test post-test design with a control group, and models the amount of change as an individual parameter. The proposal is applied to an empirical study in personality, and some interesting initial results are obtained. PMID- 22047882 TI - [ROC and z-ROC analysis in recognition memory: continuous, threshold, and asymmetric models]. AB - In this research, we applied the operating characteristic of the receiver (ROC) to evaluate item-recognition memory by means of open class words (CA) and closed class words (CC). The purpose was to evaluate memory processes and models, according to the type of stimuli used: words in Spanish, classified according to grammar characteristics. To register the data, a rating scale was applied to obtain the appropriate response levels. Statistically significant differences between the processing of both types of words were obtained. We evaluated models of threshold, continuous, and unequal variance. As a result, we could contribute to the resolution of the present controversy about the models adapted to evaluate the memory of item recognition. Lastly, the differentiation and integration of the models from an empirical point of view is discussed. PMID- 22047883 TI - [Observational analysis of the free throw shot made by grassroots basketball players]. AB - This article represents an approach to the free throw from the perspective of observational methodology. Faced with the obvious difficulty of transferring quantitative data resulting from the habitual biomechanical studies to everyday sports intervention, an easily accessible observational tool has been produced which, as a main contribution, allows the detection of T-patterns in free-throw shots. As the endorsement of the usefulness of the designed observational tool, an example is presented of the results obtained in a research design that studies a selection of grassroots basketball players (11-12 years). PMID- 22047884 TI - [A new instrument to identify spatial occupancy patterns]. AB - This paper explores the potential of systematic observational methodologies and field format instruments for the analysis of spatial appropriation processes. We present an observational instrument that facilitates the registration of a number of co-ocurrent variables related to different levels of responses (types of users, activities and environmental variables), which was used in an exploratory analysis of occupancy patterns in a public square in Barcelona. A sequential analysis revealed distinct patterns of use in different areas within the space, and at different moments during the day. These strategies offer important new opportunities to describe spatial occupancy patterns. PMID- 22047885 TI - [Spanish adaptation of the Need for Closure Scale]. AB - The Need for Cognitive Closure (NCC) refers to the motivation to seek and maintain a definitive answer to a given problem. This mental closure allows people to avoid confusion, ambiguity and uncertainty. The NCC plays a critical role in a variety of processes of diverse nature, including intra-personal (e.g., the higher the NCC, the less generation of hypothesis), inter-personal (e.g., decreased empathy), intra-group (e.g., increased desire for consensus), and inter group (increased in-group favouritism) phenomena. The goal of the present research was to provide a Spanish adaptation of Antonio Pierro and Arie Kruglanski's Revised NCC Scale (2005, Rev NfCS), examining the reliability and the validity of participants' scores. In the present studies, it was found that the Spanish version of the scale had acceptable internal reliability and adequate factor structure (Study 1), as well as acceptable test-retest reliability and adequate discriminant validity with regard to the scores in another measure of individual differences such as the Need for Cognition (NC, Study 2). PMID- 22047886 TI - [Psychometric analysis of the AF5 multidimensional scale of self-concept in a sample of adolescents and adults in Catalonia]. AB - The aim of this study is to carry out a psychometric study of the AF5 scale in a sample of 4.825 Catalan subjects from 11 to 63 years-old. They are students from secondary compulsory education (ESO), from high school, middle-level vocational training (CFGM) and from the university. Using a principal component analysis (PCA) the theoretical validity of the components is established and the reliability of the instrument is also analyzed. Differential analyses are performed by gender and normative group using a 2 x 6 factorial design. The normative group variable includes the different levels classified into 6 sub groups: university, post-compulsory secondary education (high school and CFGM), 4th of ESO, 3rd of ESO, 2nd of ESO and 1st of ESO. The results indicate that the reliability of the Catalan version of the scale is similar to the original scale. The factorial structure also fits with the original model established beforehand. Significant differences by normative group in the four components of self-concept explored (social, family, academic/occupational and physical) are observed. By gender, significant differences appear in the component of physical self-concept, academic and social but not in the family component. PMID- 22047888 TI - Desire for sons and subsequent fertility in rural India. A 20-year longitudinal study. AB - This paper compares the desired fertility of rural Indian women in 1987 with their actual fertility in 2007. Seventy-one respondents who stated definite fertility intentions and had fewer children than desired in 1987 were re interviewed 20 years later, as part of a larger study. The results indicated that these women had fewer children than intended and stopped childbearing once they reached, or approximated, their desired number of sons. The majority had been sterilized, indicating broad acceptance of lower fertility among rural women and the success of India's family planning efforts, although the practice of sex determination seems also to have played a role. These findings echo those of an earlier longitudinal study of reproductive intentions and outcomes in the same community, demonstrating the persistence of son preference in determining reproductive behaviour, even in the context of low overall fertility. The paper concludes with a discussion of the policy and programme implications of the study's findings. PMID- 22047890 TI - Duodenal myotomy blocks reduction of meal size and prolongation of intermeal interval by cholecystokinin. AB - We have shown that vagotomy (VGX) attenuates the reduction of meal size (MS) produced by cholecystokinin (CCK) -8 and -33 and that celiaco-mesenteric ganglionectomy (CMGX) attenuates the prolongation of the intermeal interval (IMI) produced by CCK-33. Here, we report the following novel data. First, by determining the distribution of CCK(1) receptor messenger RNA, which mediates reduction of MS and prolongation of IMI by CCK, in seven regions of the gastrointestinal tract in the adult rat we found that the duodenum contains the highest concentration of this receptor in the gut. Second, based on the previous finding we performed a unique surgical technique known as duodenal myotomy (MYO), which severs all the nerves of the gut wall in the duodenum including vagus, splanchnic and enteric nerves. Third, we determined MS and IMI in duodenal MYO rats in responses to endogenous CCK-58 released by the non-nutrient, trypsin inhibitor, camostat and CCK-8 to test the possibility that the duodenum is the site of action for reduction of MS and prolongation of IMI. We found that, similar to the previous work reported by using CCK-8 and MS, duodenal MYO also blocked reduction of MS by camostat. Forth, duodenal MYO blocked prolongation of IMI by camostat. As such, our current results suggest that the duodenum is the gut site that communicates both feeding signals of endogenous CCK, MS and IMI, with the brain through vagal and splanchnic afferents. PMID- 22047889 TI - Concordance of randomized and nonrandomized studies was unrelated to translational patterns of two nutrient-disease associations. AB - OBJECTIVE: There are several examples in nutrition of discordance between the results of observational studies and randomized controlled trials (RCTs). We hypothesized that this discordance is attributable to differences in the translational paths of nutrient-disease associations. Translational paths can be assessed using citation analysis. STUDY DESIGN AND SETTING: We compared the characteristics of citation networks using examples, where RCTs and observational studies agreed (long-chain n-3 polyunsaturated fatty acids [n-3 PUFA]) or disagreed (vitamin E). We performed systematic reviews in each example, constructed citation networks, and compared them with respect to the number of articles and citation relationships between them, as well as the distribution of articles' hub and authority scores. RESULTS: For n-3 PUFA, meta-analyses of 14 RCTs and 10 observational studies both suggested that higher intake was associated with lower cardiovascular mortality. For vitamin E, the meta-analysis of 14 RCTs excluded a clinically significant effect, whereas 14 observational studies reported a significant inverse association. The respective citation networks consisted of 392 (n-3 PUFA) and 351 (vitamin E) articles. No differences between the characteristics of the two networks were identified. There was no evidence that the observational studies predated RCTs in the translational process in either example. CONCLUSION: In the two examples, citation network characteristics do not predict concordance in the results of observational studies and RCTs. PMID- 22047891 TI - Dynamic susceptibility contrast-enhanced first-pass perfusion MR imaging in patients with subclinical hepatic encephalopathy. AB - BACKGROUND AND PURPOSE: Subclinical hepatic encephalopathy (SHE) is frequently reported on single-photon emission computed tomography (SPECT), but is rarely described with magnetic resonance (MR) techniques. This study aimed to investigate hemodynamic changes in brain basal ganglia in patients with SHE using dynamic susceptibility contrast (DSC)-enhanced MR perfusion imaging. METHODS: Twelve patients with SHE and ten age- and education-matched volunteers agreed to undergo MR examination. The scanning protocol included conventional anatomical images and DSC-enhanced perfusion MR imaging. Using MGH perfusion software, parameter maps of cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were created. The bilateral caudate nucleus head, globus pallidus, putamen and thalamus were selected as regions of interest (ROI), with ipsilateral white matter of the frontal lobe used as reference. Ratios (ROI versus ipsilateral white matter in frontal lobe) for CBF, CBV and MTT in the patient group were compared with those in the control group. RESULTS: The CBF ratios for every ROI were higher in SHE patients versus the controls. Statistically, significant increases were detected in the left globus pallidus, putamen and thalamus (P<0.05). For MTT, the reduction in values reached statistical significance in the right head of the caudate nucleus and bilateral thalamus (P<0.05). CBV values were not significantly different compared with those of the control group (P>0.05). CONCLUSION: Increased CBF and decreased MTT values in the basal ganglia and thalamus were identified in patients with SHE. The CBF increase was compatible with the idea that the CBF is redistributed from cortical areas to the basal ganglia structures. PMID- 22047892 TI - Cataract surgery quality, streetlamps, and car keys. PMID- 22047893 TI - Retinal prostheses: current clinical results and future needs. AB - Degenerative diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP) primarily affect the photoreceptors, ultimately resulting in significant loss of vision. Retinal prostheses aim to elicit neural activity in the remaining retinal cells by detecting and converting light into electrical stimuli that can then be delivered to the retina. The concept of visual prostheses has existed for more than 50 years and recent progress shows promise, yet much remains to be understood about how the visual system will respond to artificial input after years of blindness that necessitate this type of prosthesis. This review focuses on 3 major areas: the histopathologic features of human retina affected by AMD and RP, current results from clinical trials, and challenges to overcome for continued improvement of retinal prostheses. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references. PMID- 22047894 TI - Bullous keratopathy. PMID- 22047895 TI - Deep anterior lamellar keratoplasty. PMID- 22047896 TI - Deep anterior lamellar keratoplasty as an alternative to penetrating keratoplasty. PMID- 22047898 TI - Conjunctival melanoma. PMID- 22047900 TI - IOL power calculation after refractive surgery. PMID- 22047901 TI - Transmittance Curve of an IOL. PMID- 22047903 TI - Myotonic dystrophy. PMID- 22047905 TI - Effects of VMA on anti-VEGF Treatment for ARMD. PMID- 22047907 TI - Glare Secondary to Damaged IOL. PMID- 22047908 TI - Retinal detachment after bevacizumab. PMID- 22047909 TI - Enhanced prostaglandin F2alpha formation in human pregnancy and the effect of increased oily fish intake: results from the Salmon in Pregnancy Study. AB - Oily fish intake during pregnancy may reduce the risk of allergic diseases in infancy possibly by shifts in the fatty acid balance and subsequent altered prostaglandin (PG) formation. This intervention is the first study to evaluate if increased oily fish intake affects in vivo PGF(2alpha) formation during pregnancy. British pregnant women were randomised to two portions of farmed salmon weekly (n=47), or maintenance of their normal diet low in fish (n=41), from pregnancy week 20 until parturition. The concentrations of eicosapentaenoic and docosahexaenoic acids in plasma phosphatidylcholine (PC) were higher and the concentration of arachidonic acid in plasma PC was lower in the salmon group than the control group at weeks 34 and 38 of pregnancy. PGF(2alpha) formation was evaluated by urinary measurement of 15-keto-dihydro-PGF(2alpha), a major PGF(2alpha) metabolite, at 20, 34 and 38 weeks. In both the salmon and control groups urinary 15-keto-dihydro-PGF(2alpha) concentrations increased significantly during pregnancy, which may be of physiological importance. Oily fish intervention altered fatty acid concentrations but did not affect urinary 15-keto dihydro-PGF(2alpha) concentrations in pregnant women. PMID- 22047911 TI - Evaluation of radiation during EVAR performed on a mobile C-arm. AB - BACKGROUND: The aim of this study was to evaluate radiation exposure during aortic endovascular aneurysm repair (EVAR) on a mobile C-arm using a low dose and pulse mode. METHODS: We performed a retrospective analysis of a prospectively maintained database on patients undergoing EVAR. Indirect dose measurements of dose area product (DAP, mGy m2) calculated by the C-arm (OEC 9900MD), fluoroscopic time (FT), type of procedure, contrast media volume and body mass index were analysed. To confirm the correlation between direct and indirect DAP measurements, direct dose was measured with radiochromic films on a sample of 15 patients. Film grey level response was calibrated according to a reference dose measurement performed with a calibrated dosimeter. DAP and peak skin dose (PSD, Gy) were measured on each film. Correlation between DAP from direct and indirect measures, and between DAP and PSD, were analysed. RESULTS: From January 2009 to April 2011, 335 patients underwent EVAR. Complete data were available on 301 procedures including 188 bifurcated, 54 fenestrated, 28 thoracic, 20 branched and 11 aorto-uni-iliac endografts implantation. The respective median FT and DAP was 9.36 min (1.8-67) and 3 mGy m(2) (0.4-28); 27.2 min (2-69) and 7.3 mGy m(2) (1.2 29); 7.75 min (1.2-19.1) and 2 mGy m(2) (0.3-11); 42.98 min (2.4-95.4) and 15.95 mGy m(2) (2.98-77.7); 6.2 min (0.5-36.3) and 2 mGy m(2) (0.3-11). Direct DAP measurement on radiochromic films was strongly correlated with DAP values provided by the C-arm (r = 0.98). PSD correlated weakly with DAP. DAP was significantly increased (p < 0.001) in patients with a body mass index >30. Contrast media volume was significantly increased in the branched endograft group. CONCLUSION: Indirect DAP values measured by the C-arm are accurate to evaluate radiation exposure. Compared to the literature, our values for standard procedures are significantly decreased by the usage of low dose and pulse mode. DAP for fenestrated and branched procedures was comparable to published DAP values with standard procedures using a regular fluoroscopic mode. PMID- 22047910 TI - Omega-3 fatty acid deficiency increases stearoyl-CoA desaturase expression and activity indices in rat liver: positive association with non-fasting plasma triglyceride levels. AB - Although omega-3 (n-3) fatty acids negatively regulate triglyceride biosynthesis, the mechanisms mediating this effect are poorly understood, and emerging evidence suggests that stearoyl-CoA desaturase (Scd1) is required for de novo triglyceride biosynthesis. To investigate this mechanism, we determined the effects of perinatal n-3 deficiency and postnatal repletion on rat liver Scd1 mRNA expression and activity indices (liver 16:1/16:0 and 18:1/18:0 ratios), and determined relationships with postprandial (non-fasting) plasma triglyceride levels. Rats were fed conventional diets with or without the n-3 fatty acid precursor alpha-linolenic acid (ALA, 18:3n-3) during perinatal development (E0 P100), and a subset of rats fed the ALA- diet were switched to the ALA+ diet post weaning (P21-P100, repletion). Compared with controls, rats fed the ALA- diet exhibited significantly lower liver long-chain n-3 fatty acid compositions and elevations in monounsaturated fatty acid composition, both of which were normalized in repleted rats. Liver Scd1 mRNA expression and activity indices (16:1/16:0 and 18:1/18:0 ratios) were significantly greater in n-3 deficient rats compared with controls and repleted rats. Among all rats, liver Scd1 mRNA expression was positively correlated with liver 18:1/18:0 and 16:1/16:0 ratios. Plasma triglyceride levels, but not glucose or insulin levels, were significantly greater in n-3 deficient rats compared with controls and repleted rats. Liver Scd1 mRNA expression and activity indices were positively correlated with plasma triglyceride levels. These preclinical findings demonstrate that n-3 fatty acid status is an important determinant of liver Scd1 mRNA expression and activity, and suggest that down-regulation of Scd1 is a mechanism by which n-3 fatty acids repress constitutive triglyceride biosynthesis. PMID- 22047912 TI - Clinical characteristics, treatment and outcome of childhood Burkitt's lymphoma at the Uganda Cancer Institute. AB - Burkitt's lymphoma (BL) is a major cause of death among Ugandan children. We studied clinical characteristics and outcomes of childhood BL over time at the Uganda Cancer Institute (UCI). A total of 1217 children (766 boys, 451 girls, mean age 6.69 years) diagnosed with BL between 1985 and 2005 were included. There were no significant changes in the proportion of boys and girls diagnosed, or in mean age at diagnosis. Facial tumor (n=945, 77.65%) and abdominal disease (n=842, 69.19%) were the most common presentations. The proportion of children presenting with hepatic mass, malignant pleocytosis, and advanced-stage (stage C and D) BL increased during the study period (P<0.01). A total of 1085 children out of 1206 (89.97%) received at least one cycle of chemotherapy, and 832 of 1099 (75.71%) demonstrated objective response (i.e. complete or partial remission). The most common symptoms at BL diagnosis were fever (n=621, 51.03%), anemia (n=593, 48.73%), and weight loss (n=588, 48.32%). Significant increases in the proportion of children with fever, and significant changes in the proportion of children with anemia, night sweats and severe infection were observed. HIV positivity was 3.87%, but no substantial differences in the proportion of HIV-positive children were observed. Mortality was not significantly different over time: it was similar in boys and girls, higher in older children (compared with younger ones), in those with advanced-stage BL, and HIV-positive children, but lower in children with facial tumors compared with other tumor presentations, and among those who received chemotherapy. PMID- 22047913 TI - The challenge of designing a post-critical illness rehabilitation intervention. AB - Post-ICU morbidity is an important issue for patients, families, and the health care system. Elliott and colleagues outlined the results from their novel report of the very first home-based physiotherapy program to be tested in survivors of critical illness. The authors described an explicit intervention, which included a self-instruction exercise manual, trainer visits, and telephone follow-up, with excellent internal validity and yet no difference in outcome measures at 26-week follow-up. These results are discussed in the context of risk stratification/individual tailoring of post-ICU programs to patient and family needs and suggest that the collection of multiple simultaneous outcome measures across functional, neuropsychological, caregiver, and health-care utilization domains may offer additional insight into the benefits of post-rehabilitation programs. PMID- 22047914 TI - Adsorption of cadmium(II) on humic acid coated titanium dioxide. AB - The rapid increase in nanotechnology has led to growing concerns on environmental effects and health risks of nanoparticles (NPs). Many studies investigated the adsorption of toxic pollutants on NPs; however, the interaction between heavy metals and natural organic matter (NOM) coated metal oxide NPs was scarcely studied. In this study, using humic acid (HA) as model NOM, the adsorption of Cd(II) on humic acid coated titanium dioxide (HA-TiO(2)) NPs was investigated. Solution parameters such as pH and salinity were investigated to exploit the mechanisms. Our results demonstrated that the adsorption isotherms of Cd(II) to both TiO(2) and HA-TiO(2) complied well with Freundlich model. q(e) values increased with pH increase, mainly due to electrostatic attraction, whereas q(e) values increased initially and then decreased at 100 mmol L(-1) with salinity increase, mainly due to complexation and electrostatic effects. It is noteworthy that an overall trend of higher Cd(II) adsorption was observed on HA-TiO(2) compared to that on TiO(2), implying that HA coating might modify bioavailability of heavy metals in aquatic environment. The possible adsorption mechanisms in views of electrostatic interactions and covalent effects were interpreted, and the X-ray photoelectron spectroscopy (XPS) results also verified the possible mechanisms. PMID- 22047915 TI - Facile synthesis and multicolor luminescent properties of uniform Lu2O3:Ln (Ln=Eu3+, Tb3+, Yb3+/Er3+, Yb3+/Tm3+, and Yb3+/Ho3+) nanospheres. AB - Multicolor Lu(2)O(3):Ln (Ln=Eu(3+), Tb(3+), Yb(3+)/Er(3+), Yb(3+)/Tm(3+), and Yb(3+)/Ho(3+)) nanocrystals (NCs) with uniform spherical morphology were prepared through a facile urea-assisted homogeneous precipitation method followed by a subsequent calcination process. X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectrum (EDS), Fourier transformed infrared (FT-IR), thermogravimetric and differential thermal analysis (TG-DTA), and photoluminescence (PL) spectra as well as kinetic decays were employed to characterize these samples. The XRD results reveal that the as prepared nanospheres can be well indexed to cubic Lu(2)O(3) phase with high purity. The SEM images show the obtained Lu(2)O(3):Ln samples consist of regular nanospheres with the mean diameter of 95 nm. And the possible formation mechanism is also proposed. Upon ultraviolet (UV) excitation, Lu(2)O(3):Ln (Ln=Eu(3+) and Tb(3+)) NCs exhibit bright red (Eu(3+), (5)D(0)->(7)F(2)), and green (Tb(3+), (5)D(4)->(7)F(5)) down-conversion (DC) emissions. Under 980 nm NIR irradiation, Lu(2)O(3):Ln (Ln=Yb(3+)/Er(3+), Yb(3+)/Tm(3+), and Yb(3+)/Ho(3+)) NCs display the typical up-conversion (UC) emissions of green (Er(3+), (4)S(3/2),(2)H(11/2) >(4)I(15/2)), blue (Tm(3+), (1)G(4)->(3)H(6)) and yellow-green (Ho(3+), (5)F(4), (5)S(2)->(5)I(8)), respectively. PMID- 22047916 TI - The effect of polymer adsorption on the wetting properties of partially hydrophobized magnetite. AB - Upon reverse flotation of iron ore, the surface of the iron ore concentrate may become partially hydrophobized due to adsorption of flotation collector, which is facilitated by the calcium ions present in the process water. Hydrophobic areas on the concentrate surface may introduce problems in subsequent pelletization of the concentrate. A possible way to restore the wettability of the surface could be by modifying the surface with a hydrophilic polymer. The effect of hydrophilic polymers of different types, viz. cationic, anionic, and non-ionic, on the wettability of the magnetite surface after adsorption of a surfactant was investigated. Although all the polymers could adsorb on magnetite at pH 8.5, the contact angle measurements revealed that only anionic ammonium polyacrylate could decrease the contact angle of synthetic magnetite after surfactant adsorption to a level close to that of as-synthesized magnetite. Such effect was probably achieved due to shielding of the hydrophobic surfactant chains from the aqueous phase by hydrophilic polyacrylate molecules. The fact that polyacrylate adsorption on magnetite occurred via calcium ions makes polyacrylate suitable for application in calcium-rich process water. The results presented in this work illustrate that ammonium polyacrylate could be successfully used to improve the wettability of magnetite after adsorption of surfactants. PMID- 22047917 TI - Self-generated hierarchically porous titania with high surface area: photocatalytic activity enhancement by macrochannel structure. AB - Various hierarchical porous titania with high surface area over 600 m(2)/g have been synthesized via a spontaneous self-formation process from titanium alkoxides by a water adjusting approach using acetonitrile as reaction medium. The reactivity of metal alkoxides and the water content in acetonitrile medium on the resultant structure have been investigated. The porosities of the products were characterized by SEM, TEM and N(2) adsorption-desorption measurements. The observation on the evolution of porous structure with increasing water content in reaction system is essential for a better understanding of hierarchical porous structure formation over different length scales by this self-formation process. The creation of macro/micropores in photocatalytic titania materials has been found to enhance the photocatalytic activity due to both the action of macrochannels as light harvester and the easy diffusion effect of organic molecules. The present work shows clearly that hierarchically porous titania with the presence of macroporous structure and high surface area can be very efficient photocatalysts, suggesting their potential applications in water treatment as decontamination materials. PMID- 22047918 TI - Removal of Cd2+ from contaminated water by nano-sized aragonite mollusk shell and the competition of coexisting metal ions. AB - The potential of using nano-sized aragonite mollusk shell (nano-Bio-ARA) to remove Cd(2+) from contaminated water was investigated by comparing the sorption kinetics and isotherms with the nano-sized calcite-type mollusk shell (nano-Bio CAL) and nano-sized geological calcite (nano-Geo-CAL). Nano-Bio-ARA displayed extremely high sorption capacity to Cd(2+) (8.91mmol/g), much higher than nano Bio/Geo-CAL, and many other natural or engineered materials. The results of thermodynamic experiments indicated that the sorption of Cd(2+) on the nano-ARA was a spontaneous and endothermic process. The coexisting metals in the solution displayed competition effect to the sorption of Cd(2+) on nano-Bio-ARA in the following order: Cu(2+)>Cr(3+)>Pb(2+)>Zn(2+)>Ca(2+). EDTA impeded the sorption of Cd(2+) on nano-Bio-ARA due to its strong chelating capacity to Cd(2+) in the solution. The results demonstrate that nano-Bio-ARA is a potential high-effective material to treat Cd(2+) contaminated water. PMID- 22047919 TI - Multicolored and white-light phosphors based on doped GdF3 nanoparticles and their potential bio-applications. AB - Rare-earth-doped gadolinium fluoride nanocrystals were synthesized by a single step synthesis employing ethylene glycol as solvent. Based on X-ray diffraction studies, stabilization of hexagonal modification of GdF(3) has been inferred. The microscopic studies show formation of uniformly distributed nanocrystals (~15 nm). The nanoparticles are readily dispersible in water and show bright luminescence in colloidal solution. The luminescence properties have been investigated as a function of activator concentrations, and enhanced optical properties have been attributed to efficient energy transfer from the Gd(3+) to the activator RE(3+) ions, which has further been confirmed by steady-state and time-resolved optical studies. It has been demonstrated that on doping appropriate amount of activators in host GdF(3), a novel white-light-emitting phosphor is obtained with CIE co-ordinates and correlated color temperature (CCT) very close to broad daylight. This can have promising applications as phosphor for white-light ultraviolet-light-emitting diodes (UV-LEDs). Our experiments showed efficient labeling of human breast carcinoma cells (MCF-7) by Tb(3+)-doped GdF(3) nanoparticles. The fluorescence intensity was found to be dependent on the surface modifying/coating agent, and the results were validated using confocal microscopy in terms of localization of these functionalized nanoparticles. PMID- 22047920 TI - Humidity adsorption kinetics of a trypsin gel film. AB - This study focuses on the humidity adsorption kinetics of an isopropanol-induced and pH-triggered bovine pancreatic trypsin gel (BPTG). The BPTG was adsorbed on a gold coated Quartz Crystal Microbalance (QCM) substrate with a thickness of 376 nm. The morphology of the film was characterized using Atomic Force Microscopy (AFM). QCM was used to investigate the humidity sensing properties of the BPTG film. The response of the humidity sensor was explained using the Langmuir model. The average values of adsorption and desorption rates between 11% RH (relative humidity) and 97% RH were calculated as 2482.5 M(-1) s(-1) and 0.02 s(-1), respectively. The equilibrium constant and average Gibbs Free Energy of humidity adsorption and desorption cycles were obtained as 133,000 and -11.8 kJ/mol, respectively. PMID- 22047921 TI - Synthesis of uniform gold nanoparticles using non-pathogenic bio-control agent: evolution of morphology from nano-spheres to triangular nanoprisms. AB - Green synthesis of gold nanospheres with uniform diameter and triangular nanoprisms with optically flat surface was carried out using a non-pathogenic bio control agent Trichoderma asperellum for reduction of HAuCl(4). Kinetics of the reaction was monitored by UV-Vis absorption spectroscopy. No additional capping/complexing agent was used for stabilizing the gold nanoparticles. Evolution of morphology from pseudospherical nanoparticles to triangular nanoprisms was studied by transmission electron microscopy (TEM). It revealed that three or more pseudospheres fused to form nanoprisms of different shapes and sizes. Slow rate of reduction of HAuCl(4) by constituents of cell-free fungal extract was instrumental in producing such exotic morphologies. Isolation of gold nanotriangles from the reacting masses was achieved by differential centrifugation. PMID- 22047922 TI - Thermodynamic and structural characterization of a mixed perfluorocarbon phospholipid ternary monolayer surfactant system. AB - Pulmonary lung surfactant is a mixture of surfactants that reduces surface tension during respiration. Perfluorinated surfactants have potential applications for artificial lung surfactant formulations, but the interactions that exist between these compounds and phospholipids in surfactant monolayer mixtures are poorly understood. We report here, for the first time, a detailed thermodynamic and structural characterization of a minimal pulmonary lung surfactant model system that is based on a ternary phospholipid-perfluorocarbon mixture. Langmuir and Langmuir-Blodgett monolayers of binary and ternary mixtures of the surfactants 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2 dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and perfluorooctadecanoic acid (C18F) have been studied in terms of miscibility, elasticity and film structure. The extent of surfactant miscibility and elasticity has been evaluated via Gibbs excess free energies of mixing and isothermal compressibilities. Film structure has been studied by a combination of atomic force microscopy and fluorescence microscopy. Combined thermodynamic and microscopy data indicate that the ternary monolayer films were fully miscible, with the mixed films being more stable than their pure individual components alone, and that film compressibility is minimally improved by the addition of perfluorocarbons to the phospholipids. The importance of these results is discussed in context of these mixtures' potential applications in pulmonary lung surfactant formulations. PMID- 22047923 TI - pH-responsive interpenetrating network hydrogel beads of poly(acrylamide)-g carrageenan and sodium alginate for intestinal targeted drug delivery: synthesis, in vitro and in vivo evaluation. AB - In the present work, we synthesized pH-responsive interpenetrating network (IPN) hydrogel beads of polyacrylamide grafted kappa-carrageenan (PAAm-g-CG) and sodium alginate (SA) for targeting ketoprofen to the intestine. The PAAm-g-CG was synthesized by free radical polymerization followed by alkaline hydrolysis under nitrogen gas. The PAAm-g-CG was characterized by elemental analysis, FTIR spectroscopy and thermogravimetric analysis (TGA). The drug-loaded IPN hydrogel beads were prepared by simple ionotropic gelation/covalent crosslinking method. The amorphous nature of drug in the beads was confirmed by differential scanning calorimetry and X-ray diffraction studies. The spherical shape of the beads was confirmed by scanning electron microscopic analysis. The beads exhibited ample pH responsive behavior in the pulsatile swelling study. The ketoprofen release was significantly increased when pH of the medium was changed from acidic to alkaline. The beads showed maximum of 10% drug release in acidic medium of pH 1.2, and about 90% drug release was recorded in alkaline medium of pH 7.4. Stomach histopathology of albino rats indicated that the prepared beads were able to retard the drug release in stomach leading to the reduced ulceration, hemorrhage and erosion of gastric mucosa. PMID- 22047924 TI - Predictive factors of skip metastases to lateral neck compartment leaping central neck compartment in papillary thyroid carcinoma. AB - Skip metastasis, referred to as leaping metastasis to the lateral neck without associated lymphadenopathy in the central compartment (level VI), can occur in patients with papillary thyroid carcinoma (PTC). However, there have been few studies on its predictive value in PTC patients. We reviewed the medical records of 90 patients who underwent simultaneous central and lateral neck lymph node dissection for the primary treatment of lymph node metastasis in the lateral neck of PTC patients. No patient was suspected of having metastasis in the central compartment by preoperative imaging study. The frequency of skip metastasis to the lateral neck compartment without central neck metastasis was 19% (17/90). The number of metastatic lymph nodes dissected in the lateral neck of patients with and without skip metastasis was 5.1+/-2.7 and 9.5+/-2.6, respectively (P<0.001). Skip metastasis was closely associated with significantly fewer lymphovascular invasion (P=0.009) and extracapsular spread (P=0.035). Skip metastasis can occur significantly frequently in PTC patients. The presence of lymphovascular invasion, extracapsular spread, and number of positive lymph nodes dissected were inversely correlated with skip metastasis. PMID- 22047925 TI - Capsular management during hip arthroscopy: from femoroacetabular impingement to instability. AB - Advances in the ability to treat various soft-tissue and osseous pathologic conditions of the hip arthroscopically have been predicated on an improved exposure of the pathology of the central, peripheral, and peritrochanteric compartments. The management of the capsule is critical and must allow for an improved exposure without compromising stability and kinematics of the hip. Described approaches have included capsulectomy, limited capsulotomy, extensile capsulotomy, capsular plication, and capsular shift. The selected approach must consider various factors, including symptomatic complaints, underlying hyperlaxity, specific mechanical pathology, and surgical expertise. Universally using a single technique without consideration of the complex mechanical and anatomic factors unique to each patient may result in incomplete treatment of the pathoanatomy or iatrogenic instability. This article reviews the anatomy of the hip capsule and provide a diagnosis-based consideration of capsular management during hip arthroscopy. The senior author's preferred techniques are also presented. PMID- 22047926 TI - Evaluation of analgesic efficacy of intra-articular bupivacaine, bupivacaine plus fentanyl, and bupivacaine plus tramadol after arthroscopic knee surgery. AB - PURPOSE: To compare the efficacy of intra-articular (IA) bupivacaine, bupivacaine fentanyl, and bupivacaine-tramadol for relief of postoperative pain after arthroscopic knee surgery. METHODS: In a randomized double-blind design, 60 adult American Society of Anesthesiologists class I or class II patients undergoing elective arthroscopic knee surgery under general anesthesia were randomized to 3 groups: all received 30 mL of 0.25% bupivacaine, plus either 1 mL of normal saline solution (group I), 1 mL (50 MUg) of fentanyl (group II), or 1 mL (50 mg) of tramadol (group III). Pain was assessed by use of a 100-mm visual analog scale (VAS) at 0, 1, 2, 4, 6, and 8 hours postoperatively. Intramuscular diclofenac sodium was used as rescue analgesic. Postoperative adverse effects were noted. RESULTS: The mean VAS pain scores were the lowest for group II, intermediate for group III, and highest for group I. There was a significant main effect for group differences on pain scores (F = 41.138, P < .001). The main effect for the time factor was also significant (F = 6.097, P < .001). However, both group II and group III were comparable and both were superior to group I with regard to supplementary analgesia in terms of (1) number of patients receiving it, (2) total consumption during the study period, and (3) time to first supplementary analgesic requirement. The incidence of adverse event was comparable among the 3 groups. CONCLUSIONS: On the primary outcome measure (VAS pain score), both bupivacaine with fentanyl and bupivacaine with tramadol were better than IA bupivacaine, and bupivacaine with fentanyl was better than that with tramadol. However, both the combinations were comparable to each other with regard to the secondary outcome measure (supplementary analgesic requirement). Thus IA bupivacaine-fentanyl appears to be the best combination for relief of postoperative pain in patients undergoing arthroscopic knee surgery, followed by IA bupivacaine-tramadol. LEVEL OF EVIDENCE: Level I, randomized controlled trial. PMID- 22047927 TI - Inadequate use of prophylaxis against venous thromboembolism in Danish medical departments. AB - INTRODUCTION: Venous thromboembolism (VTE) constitutes a major risk factor in hospitalized acutely ill medical patients. It has been demonstrated in numerous papers that by using different forms of prophylaxis, a significant reduction of the incidence of VTE can be achieved. In this article we assessed the tendencies in the use of venous thromboprophylaxis (TP) at internal medicine departments in Denmark. The results were compared with results from a similar study conducted in 2005. MATERIAL AND METHODS: All medical departments in Denmark received a two page questionnaire on TP. The recipients were asked to evaluate the frequency, use of local instructions, form of administration, side-effects and duration of TP at their departments. One reminder was sent out. RESULTS: A total of 188 responses were received (90% response rate), 16 were excluded. Virtually all departments indicated that they used TP (92%). At intensive care units, the TP was used according to local guidelines at 77% of the wards and at the other subspecialties of internal medicine, TP was used in less than 50%. By far the most frequently used prophylaxis method was low molecular weight heparin, which was used by more than 80% of the departments. Side-effects, most often superficial bleeding and haematomas, were reported in 25% of the cases. The following serious side-effects were reported: heparininduced thrombocytopenia (n = 2), stroke (n = 1) and gastrointestinal bleeding (n = 3). No difference was observed between the hospitals of larger cities and those of smaller cities. CONCLUSION: In Denmark, no significant increase in the use of TP at internal medicine departments has been observed since 2005. The guideline's strong recommendation of TP is still not reflected in daily practice. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. PMID- 22047928 TI - Medical graduates feel well-prepared for clinical work. AB - INTRODUCTION: The purpose of this study was to assess the coherence between the undergraduate medical program at Aarhus University and the foundation year. MATERIAL AND METHODS: This cross-sectional questionnaire survey included 503 doctors graduated from Aarhus University from the winter of 2007/2008 to the summer of 2009. RESULTS: The response rate was 73%. Approximately 73% of the respondents were in their foundation year or their first year of specialist training and 83% generally felt well-prepared. Respondents found that most of the learning outcomes of the undergraduate medical curriculum at Aarhus University are important for junior doctors. More than 90% of the respondents estimated that they were sufficiently prepared when it came to core outcomes such as history taking and physical examination. Five issues diverged considerably in importance stated and preparedness experienced: suggestion of diagnoses, initiation of treatment, pharmacotherapy, handling of own emotions and structuring of own learning. Also, 40% stated that their clerkships had only had little value in preparing them for their foundation year. CONCLUSION: Overall, graduates felt well-prepared and characterized the education coherent. However, the study raises major questions concerning clerkships and competence in treatments, pharmacotherapy and the more personal aspects of professionalism. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. PMID- 22047929 TI - Combination of cancer antigen 125 and carcinoembryonic antigen can improve ovarian cancer diagnosis. AB - INTRODUCTION: The purpose of the present study was to evaluate the ability of the tumour marker carcinoembryonic antigen (CEA) in combination with cancer antigen 125 (CA-125) to differentiate between malignant ovarian and malignant non-ovarian disease. MATERIAL AND METHODS: All patients attending the Department of Gynaecology, Herlev Hospital, who underwent an "ovary lab investigation" between 1 January 2006 and 31 December 2008 were included. Among a total of 640 patients, 355 had a malignant diagnosis. Preoperative CEA and CA-125 serum levels and final malignant diagnosis after surgery were extracted from the medical records. RESULTS: Among the patients with CEA levels > 5 ng/ml, 68% had non-ovarian malignancies. This test identified 39% of the non-ovarian cancers correctly. In patients with a CA-125/CEA ratio > 25, an ovarian cancer was found in 82%. The CA 125/CEA test identified 63% of the non-ovarian cancers correctly. The specificity increased to around 85% when the cut-off value of the CA-125/CEA ratio was increased from 25 to 100. CONCLUSION: In patients with an undiagnosed tumour in the pelvis, the CA-125/CEA ratio may be used to preoperatively identify a substantial fraction of patients with non-ovarian malignancies. In the study population, the specificity rose to 85% when the cut-off value was increased from 25 to 100, which highlights the usefulness of a higher cut-off level. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. PMID- 22047930 TI - A substantial number of scientific publications originate from non-university hospitals. AB - INTRODUCTION: As we found no recent published reports on the amount and kind of research published from Danish hospitals without university affiliation, we have found it relevant to conduct a bibliometric survey disclosing these research activities. MATERIAL AND METHODS: We retrieved all scientific papers published in the period 2000-2009 emanating from all seven Danish non-university hospitals in two regions, comprising 1.8 million inhabitants, and which were registered in a minimum of one of the three databases: PubMed MEDLINE, Thomson Reuters Web of Science and Elsevier's Scopus. RESULTS: In 878 of 1,252 papers, the first and/or last author was affiliated to a non-university hospital. Original papers made up 69% of these publications versus 86% of publications with university affiliation on first or last place. Case reports and reviews most frequently had authors from regional hospitals as first and/or last authors. The total number of publications from regional hospitals increased by 48% over the 10-year period. Publications were cited more often if the first or last author was from a university hospital and even more so if they were affiliated to foreign institutions. Cardiology, gynaecology and obstetrics, and environmental medicine were the three specialities with the largest number of regional hospital publications. CONCLUSION: A substantial number of scientific publications originate from non university hospitals. Almost two thirds of the publications were original research published in international journals. Variations between specialities may reflect local conditions. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. PMID- 22047931 TI - Good experiences with an audience response system used in medical education. AB - INTRODUCTION: Audience response systems (ARS) are increasingly being used to heighten participants' involvement. Knowledge of technical and pedagogical challenges is, however, limited. The purpose of this paper is to evaluate ARS as a tool for 1) evaluation, 2) knowledge testing, 3) attention raising and 4) discussion stimulation. MATERIAL AND METHODS: ARS was used 33 times at four different courses. Data include voting results, observations, questionnaires and interviews. RESULTS: A total of 215 participants and 12 teachers were included. The majority of the participants found ARS suitable for course evaluation. The teachers found it useful for obtaining the results immediately and thereby for receiving feedback on their own teaching. The participants and the teachers found ARS suitable for knowledge testing. ARS was used as an instrument to increase activity and attention. The system was found to increase the level of concentration and the interactivity. ARS was used to initiate discussions. The participants found that the questions could be a good starting point for discussion. The teachers found it challenging to comment on answers. Our experiences are that thorough planning and preparation is needed for the successful implementation of ARS. CONCLUSION: Our experiences indicate that ARS is suitable for course evaluation. Overall, we find ARS a valuable technology that may stimulate discussion and support learning, but teachers need to be technically and pedagogically well prepared to use the tool. The use of ARS does not in itself entail that the quality of the teaching increases. PMID- 22047932 TI - Validation of the Danish version of Oxford Shoulder Score. AB - INTRODUCTION: The Oxford Shoulder Score (OSS) is a patient-administered condition specific questionnaire for patients with degenerative or inflammatory shoulder disease. The purpose of this study was to validate a Danish translation of the OSS and to compare it with the Constant Score (CS). MATERIAL AND METHODS: A total of 102 consecutive patients referred to our shoulder unit were recruited for the study. The OSS was translated into Danish according to recommendations presented by Guillemin and co-workers. We established the psychometric properties of the scoring system. Test-retest reliability was assessed by inviting 32 patients to complete another OSS 72 hours after the first test. The Bland-Altman plot was used to show absolute differences between test and retest. RESULTS: The validity expressed as a Spearman's rank correlation coefficient comparing the OSS with the CS was 0.74. The test-retest reliability correlation coefficient was 0.98. Bland Altman plots revealed limits of agreement between the scores of -4.5 and -5.4. Internal consistency tested by Cronbach's alpha was 0.93. CONCLUSION: The psychometric properties of the Danish version of OSS showed good validity and reliability with a substantial correlation between the OSS and the CS. Internal consistency was high. The OSS is recommended for the evaluation of patients with degenerative or post-traumatic shoulder diseases. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. PMID- 22047933 TI - Uncertain added value of Global Trigger Tool for monitoring of patient safety in cancer care. AB - INTRODUCTION: Monitoring patient safety is a challenging task. The lack of a golden standard has contributed to the recommendation and introduction of several methods. In 2000 the Danish Lung Cancer Registry (DLCR) was established to monitor the clinical management of lung cancer. In 2008 the Global Trigger Tool (GTT) was recommended in Denmark as a tool for the monitoring of patient safety. Ideally, the recommendation of a new tool should be preceded by a critical assessment of its added value. MATERIAL AND METHODS: Data on complications related to lung cancer surgery from the Department of Cardiothoragic Surgery at Odense University Hospital were collected using the DLCR and the GTT in 2008. The capacity of these two methods to identify complications is compared and discussed. RESULTS: A total of 59 complications were registered in the DLCR, while 58 complications were registered using the GTT. The two methods were equally good at identifying complications, but the DLCR seemed to be borderline significantly better at detecting arrhythmia, while the GTT was significantly better at detecting "other events". CONCLUSION: Nearly half of the adverse events identified with the GTT were complications which were also registered by type in the DLCR. The two methods were almost equally good at identifying specific types of complications, but the GTT identified more "other events". The majority of these events were well-known to clinicians. The comparison illustrates why the implementation of new methods should be preceded by critical assessment. In this case, it is crucial to assess whether the current method should be modified by the addition of more patient safety indicators rather than by introducing a new method that partly duplicates existing data. PMID- 22047934 TI - Macrolide overuse for treatment of respiratory tract infections in general practice. AB - INTRODUCTION: High consumption of macrolides has been linked to increased macrolide resistance in the common pathogens of respiratory tract infections (RTIs). According to Danish recommendations, penicillin is the first-choice treatment for RTIs and macrolides should only be prescribed when a patient is allergic to penicillin or for treatment of mycoplasma pneumonias. The aim of the present study was to explore the prescription of macrolides for different RTIs to patients without penicillin allergy in general practice in Denmark. MATERIAL AND METHODS: This was a cross-sectional study. Data were collected during a three week period in January 2008 as part of the EU-funded project Health Alliance for Prudent Prescribing, Yield and Use of Antimicrobial Drugs in the Treatment of Respiratory Tract Infections (HAPPY AUDIT). A total of 102 Danish general practitioners participated and registered patients with RTIs according to the Audit Project Odense method. RESULTS: A total of 3,904 patients with RTIs were registered and 1,351 patients received antibiotics. Among these, 198 patients received a macrolide. In all, 136 patients received a macrolide without being allergic to penicillin. This proportion was highest for patients diagnosed with acute otitis media (71%), acute bronchitis (71%) or pneumonia (76%). CONCLUSION: Overall, there was a considerable overuse of macrolide for treatment of all types of RTIs. The macrolide overuse found in this study cannot be explained by the aetiology of Mycoplasma pneumoniae since there was no epidemic in 2008. FUNDING: Data for the macrolide study were collected from the HAPPY AUDIT study which was funded by the EU. The two first-authors each received DKK 30,000 from the PLU foundation for their work on the article. TRIAL REGISTRATION: The HAPPY AUDIT method was registered and published in the BioMed Central. PMID- 22047935 TI - Modern treatment strategies in rheumatoid arthritis. AB - The main aim of the thesis was to evaluate the impact of modern treatment strategies on disease activity and disease course in patients with rheumatoid arthritis (RA), and to identify predictors for treatment response. Two different treatment strategies were investigated: (A) Aggressive, conventional treatment aiming at achieving inflammatory control in patients with recent-onset RA and (B) Treatment with tumour necrosis factor alpha (TNFalpha) inhibitors in patients with RA, who had an incomplete response to conventional treatment. (A) was studied in a randomized, placebo-controlled clinical trial (CIMESTRA), whereas (B) was investigated in an observational, nationwide cohort study (the DANBIO database). The main findings were: 1. Treatment strategy (A) with methotrexate (MTX) and injections of glucocorticoids into swollen joints had rapid and sustained effect and reduced disease activity and halted joint damage. Addition of cyclosporine during the first 2 years reduced disease activity for as long as it was given, but had no effect on the development of joint damage. After 5 years, the majority of the patients was in remission and had no progression of structural joint damage. 2. Bone marrow oedema by Magnetic resonance imaging (MRI) scans of the wrists predicted the development of structural joint damage 2 to 5 years later (based on x-rays). Anti-CCP antibodies and structural joint damage at the start of treatment were also independent predictors for joint damage after 5 years. 3. Routine registration of adverse events observed in patients who received treatment with etanercept or infliximab (TNFalpha inhibitors) in the DANBIO database picked up twice as many serious adverse events than the spontaneous, mandatory reports to the Danish Medicines Agency. 4. Despite changes in prescription practice for the treatment with TNFalpha inhibitors in clinical practice from year 2000 to year 2005 towards less stringent treatment criteria, DANBIO data showed an improved treatment response. 5. High age, low functional status and concomitant treatment with prednisolone were negative predictors of a EULAR good response and remission after 6 months of treatment with TNFalpha inhibitors in clinical practice. 6. In patients, who were naive to treatment with TNFalpha inhibitors, significant differences between drugs were observed regarding treatment responses and adherence to therapies. Infliximab had the lowest treatment response, remission rates and adherence to therapy. Adalimumab had the highest treatment response and remission rates, whereas etanercept had the highest adherence. In conclusion, the results from the CIMESTRA trial and the DANBIO database showed that an aggressive treatment strategy with conventional drugs and intra-articular injections with betamethasone effectively controlled disease activity and prevent structural joint damage in patients with early RA. TNFalpha inhibitors were efficacious in clinical practice in the treatment of RA patients that had failed conventional treatment. Differences between the TNFalpha inhibitors regarding efficacy and drug adherence were found. Predictors of disease course and treatment response were identified. PMID- 22047936 TI - Psoriasis and Cardiovascular Disease: epidemiological studies. AB - Atherosclerosis and PS are prevalent chronic immunoinflammatory diseases with pathophysiological, clinical and epidemiological similarities. Results suggest that PS may be an independent risk factor for cardiovascular disease. Participation of similar immunoinflammatory and prothrombotic mechanisms in PS and cardiovascular disease is supported by evidence that treatment with methotrexate in patients with PS is associated with reduced cardiovascular risk. Furthermore, PS is associated with surrogate markers of cardiovascular disease, e.g. endothelial dysfunction and coronary calcification, and with markers of increased platelet activity. However, results of epidemiological studies of the risk of cardiovascular disease in PS have been conflicting, and surveillance bias has been proposed to contribute to the observed association. Although similar considerations of shared immunoinflammatory pathways with PS can be applied to AF and VTE very little is known about the interaction between PS and these common diseases. With the underlying hypothesis that PS had detrimental effects on all prespecified adverse cardiovascular endpoints the objective of the current thesis was to examine in these patients: 1) the risk of atherothrombotic events and compare it with the risk in patients with DM; 2) the risk of AF and ischaemic stroke; 3) the risk of VTE; and 4) the prognosis after first-time MI. By use of the unique Danish nationwide registries approximately 40,000 patients with PS, including approximately 3000 patients with severe PS were identified in the study period 1997-2006. Paper I provided a comparison of cardiovascular risk between patients with PS, approximately 127,000 patients with DM, and the general population, respectively. Patients with PS were at increased risk of all endpoints including, MI, stroke, invasive coronary revascularization, cardiovascular death, and a composite cardiovascular endpoint (MI, stroke, and cardiovascular death). For the composite endpoint the rate ratios (RRs) were 1.20 (95% confidence interval [CI] 1.14-1.25), 1.58 (CI 1.36-1.85), and 1.59 (CI1.56 1.63) for mild PS, severe PS, and DM, respectively. Paper II documented an up to 2.5 fold increase in risk of AF and ischaemic stroke in patients with PS, with the highest risk estimates for young patients with severe disease. The main results of paper III were that patients with PS had an increased risk of VTE with RR 1.35 (CI 1.21-1.49) and RR 2.06 (CI 1.63-2.61) for mild and severe PS, respectively. Paper IV on post-MI prognosis included 615 patients with PS and a recent MI. The results documented that after first-time MI, these patients had an increased risk of a composite of recurrent MI, stroke, and cardiovascular death with hazard ratio 1.26 (CI 1.12-1.41) as compared to patients without PS. In conclusion, this thesis demonstrated that all patients with PS were at increased risk of atherothrombotic events and that the risk with severe PS was comparable to that of patients with DM. Furthermore, the thesis provided novel evidence of PS as a possible risk factor for AF and VTE. Finally, we demonstrated an association between PS and adverse prognosis following first-time MI. The results add importantly to evidence indicating that PS is an independent cardiovascular risk factor and should form the background for studies of interventions aimed at improved primary and secondary prevention of cardiovascular disease in patients with PS. PMID- 22047937 TI - A model for educational simulation of the evolution of uterine contractions during labor. AB - Electronic fetal monitoring remains an important tool in labor ward settings, providing continuous information on fetal heart rate and maternal uterine contractions. A prompt detection of abnormalities in these signals is essential for the timely resolution of situations that may put both mother and fetus at risk. Uterine contraction signals provide information that is important to evaluate the onset and progress of labor, as well as the significance of certain fetal heart rate abnormalities. We present a model for educational simulation of the spontaneous evolution of uterine contractions during labor, which combines a previously published signal generator with literature-based pre-programmed scripts for educationally relevant scenarios. This model is an essential component of a high-fidelity simulator of intrapartum emergencies, aimed to improve the competency of healthcare providers. Real and simulated tracings were presented to three independent clinical experts who judged simulated signals to be indistinguishable or negligibly different from real tracings. PMID- 22047938 TI - Hepatosplenic gamma-delta T-cell lymphoma. AB - Hepatosplenic T-cell lymphoma (HSTL) is a rare and aggressive extranodal lymphoma derived mostly from cytotoxic gammadelta T-cells. The peak incidence is in adolescents and young adults, and is more common in males. Up to 20% of HSTL arise in the setting of chronic immune suppression, most commonly solid organ transplantation or prolonged antigenic stimulation. Patients present with systemic symptoms (fever), abdominal pain, weakness, and marked hepatosplenomegaly in the absence of lymphadenopathy. Patients usually manifest marked thrombocytopenia, often with anaemia and leucopenia, a leukemic phase, and bone marrow involvement in 80% of cases. Lactate dehydrogenase levels are usually markedly elevated. HSTL exhibits a marked chemoresistance to currently used regimens, a rapidly progressive behavior, and dismal prognosis. Patients with post-transplant HSTL exhibit an especially poor outcome. Standard treatment has yet to be established. Anthracycline-based chemotherapy is associated with a satisfactory response in two thirds of patients, but poor long-term results. Complete remission is extremely uncommon, and most patients die from lymphoma within two years of diagnosis. A prognostic correlation between outcome and degree of thrombocytopenia has been reported. Relapsing disease is usually chemorefractory and fast growing, and patients' performance status and clinical conditions are poor. These aspects, as well as the lack of drugs with proven activity against HSTL, render salvage treatment almost impossible. A few cases of HSTL successfully treated with autologous or allogeneic stem-cell transplantation have been reported. The use of 2'-deoxycoformycin and other targeted therapies, such as alemtuzumab, anti-gammadelta TCR monoclonal antibodies, and anti-CD44 therapy, have shown promising results in anecdotal reports. PMID- 22047939 TI - The effect of short-term use of the Guardian RT continuous glucose monitoring system on fear of hypoglycaemia in patients with type 1 diabetes mellitus. AB - AIM: This study examines whether the short-term use of a continuous glucose monitor (CGM) can reduce the fear of hypoglycaemia in individuals with type 1 diabetes mellitus (T1DM). METHODS: Twelve participants with T1DM were fitted with a Guardian(r) REAL-Time CGM and assigned to either an alarm (low glucose alarm set at 4.5 mmol/L) or no alarm condition for 3 days, with both treatments administered following a counterbalanced study design. The participants completed the Hypoglycaemia Fear Survey on three separate occasions, before their CGM was fitted as well as following the alarm and no alarm conditions. RESULTS: The alarm treatment reduced the incidence of hypoglycaemic episodes (CGM readings<=3.5 mmol/L; 1.1+/-0.5 versus 1.9+/-0.5; mean+/-SEM) and the relative time spent below this hypoglycaemic threshold (0.9+/-0.4% versus 2.6+/-1.0%) but did not alter the fear of hypoglycaemia (78.6+/-7.0, 75.8+/-5.2 and 79.3+/-5.8 at baseline and following the alarm and no alarm treatments, respectively; p>0.05). CGM overestimated blood glucose levels by 0.8+/-0.2 mmol/L for blood glucose readings less than, or equal to, 5 mmol/L. CONCLUSIONS: Short-term use of the Guardian(r) REAL-Time CGM has no clinically significant effect on fear of hypoglycaemia possibly due, in part, to the inaccuracies of CGMs at low blood glucose levels. PMID- 22047940 TI - Psychological distress and mental disorders among Spanish diabetic adults: a case control study. AB - AIM: To compare the prevalence of psychological distress and mental disorders between diabetes and non-diabetes sufferers and to identify associated factors. METHODS: Case-control study based on data from the 2006 to 2007 Spanish National Health Survey. We identified 2193 type 2 diabetic adults. Non-diabetic controls were 1:1 matched by age-and-sex. The presence of a mental disorder was considered if subjects answered yes to the questions: "Have you suffered depression and/or anxiety over the previous 12 months?" AND "Has your medical doctor confirmed the diagnosis?". The 12-item General Health Questionnaire was used to measure psychological distress. Independent covariables included socio-demographics and heath related variables. RESULTS: Prevalence of mental disorders was 18.6% among diabetics and 16.4% among controls (adjusted OR 1.17 CI 95% 1.01-1.38). 26% of diabetics and 18.9% of the non-diabetic suffered psychological distress (adjusted OR 1.51 CI 95% 1.25-1.83). Among diabetics variables associated with suffering a mental disorder and psychological distress were: female sex, younger age, worse self rated health, comorbidity, GP visit in the last 4 weeks and ER attendance in last year. CONCLUSIONS: Diabetic adults have significantly higher prevalence of diagnosed mental disorders and psychological distress than non-diabetic subjects. Programs targeted at preventing, monitoring and controlling these mental health problems at primary care should be implemented. PMID- 22047941 TI - Streptococcus pneumoniae vaccination in older adults. AB - BACKGROUND: Streptococcus pneumoniae infections are a major cause of morbidity and mortality in older adults. Vaccination in older adults is intended to prevent S pneumoniae infections, yet little information is available regarding its efficacy in this patient population. OBJECTIVE: The aim of this article was to review the current literature to determine the efficacy and tolerability of S pneumoniae vaccination in older adults. METHODS: PubMed (1950-present) and EMBASE (1974-present) were searched using the search terms Streptococcus pneumoniae immunization, pneumococcus immunization, pneumococcus vaccine, and aged. Additional articles were identified from the reference lists of included studies. Studies were included if they reported information in older (55-<65 years) and elderly (>=65 years) adults and were related to at least 1 of the following topics: epidemiology of S pneumoniae, estimates of vaccine coverage, recommendations for vaccination, tolerability, and efficacy and/or effectiveness of vaccination against S pneumoniae. RESULTS: Six randomized controlled trials and 18 observational studies that evaluated the efficacy of pneumococcal vaccination in older and elderly adults were reviewed. Findings from evaluations of efficacy, as measured by clinical outcomes and immunogenicity, in older adults have been conflicting, with some subsets of prospective, well-controlled studies finding little benefit, whereas findings from several retrospective studies have suggested significant benefit. This discord may have been a result of the limited power of the prospective subanalyses to detect significant differences. CONCLUSIONS: In light of the potential clinical benefit and few reports of serious adverse events, vaccination in older adults is likely warranted. Prospective, well-controlled studies are needed to better quantitatively evaluate the benefit of pneumococcal vaccine in older adults. PMID- 22047942 TI - Atomic force microscopy nanoindentation of a dental restorative midifill composite. AB - OBJECTIVES: We investigated the elastic properties of one dental restoration resin composite of common use, Venus Diamond, at submicrometer spatial resolution. METHODS: We performed both nanoindentation experiments with atomic force microscopy, and microindentation experiments with a traditional indenter setup. We also used scanning electron microscopy and energy dispersive X-rays spectroscopy to better understand the correlation between properties and microscopic structure and composition. RESULTS: With atomic force microscopy we obtained quantitative evaluation of the elastic modulus (10.8 +/- 4.3 GPa), in agreement with the microindentation value (reduced modulus of 12.7 +/- 2.0 GPa), and by microindentation we also obtained an hardness value (460 +/- 109 MPa) compatible in turn with the nominal value provided by the material manufacturer (H ~ 578 MPa). The nanoindentation also revealed that no relevant difference in elasticity appears between the 5 and 10 MUm diameter filler particles and the surrounding areas, showing an excellent uniformity of the composite. In support of this finding, compositional uniformity of the material was also observed by X rays spectroscopy. We conclude that the composite contains prepolymerized particles. SIGNIFICANCE: We demonstrate that, in addition to reliable quantitative analysis, the high resolution and two-dimensional mapping capability of atomic force microscopy allows for advanced insights into the microstructure of the composite that are not accessible via traditional microindentation. PMID- 22047943 TI - Effects of silica and zinc oxide doping on mechanical and biological properties of 3D printed tricalcium phosphate tissue engineering scaffolds. AB - OBJECTIVES: To evaluate the effects of silica (SiO(2)) (0.5 wt%) and zinc oxide (ZnO) (0.25 wt%) dopants on the mechanical and biological properties of tricalcium phosphate (TCP) scaffolds with three dimensionally (3D) interconnected pores. METHODS: Scaffolds were created with a commercial 3D printer. Post sintering phase analysis was determined by X-ray diffraction. Surface morphology of the scaffolds was examined by field emission scanning electron microscopy (FESEM). Mechanical strength was evaluated with a screw driven universal testing machine. MTT assay was used for cellular proliferation characteristics and cellular morphology was examined by FESEM. RESULTS: Addition of dopants into TCP increased the average density of pure TCP from 90.8 +/- 0.8% to 94.1 +/- 1.6% and retarded the beta to alpha phase transformation at high sintering temperatures, which resulted in up to 2.5 fold increase in compressive strength. In vitro cell materials interaction studies, carried out using hFOB cells, confirmed that the addition of SiO(2) and ZnO to the scaffolds facilitated faster cell proliferation when compared to pure TCP scaffolds. SIGNIFICANCE: Addition of SiO(2) and ZnO dopants to the TCP scaffolds showed increased mechanical strength as well as increased cellular proliferation. PMID- 22047944 TI - Space madness: the dreaded disease that never was. AB - Psychiatrists working with the National Aeronautics and Space Administration in the late-1950s feared the worst of the men they examined to be America's first astronauts: that they would be impulsive, suicidal, sexually aberrant thrill seekers. The examiners, though, were surprised - and a little disappointed - when tests revealed the would-be astronauts to be sane, poised professionals able to absorb extraordinary stresses. A Space Age malady with no incidence among human populations, 'space madness' is the stuff of Hollywood: a cultural manifestation of popular fears of a lonely, dehumanizing, and claustrophobic future among the stars. PMID- 22047945 TI - Defining the adequate arterial pressure target during septic shock: not a 'micro' issue but the microcirculation can help. AB - The Surviving Sepsis Campaign guidelines suggest targeting a mean arterial pressure of at least 65 mm Hg to maintain organ perfusion pressure during septic shock. However, the optimal mean arterial pressure can be higher in patients with a history of hypertension or other vascular comorbidities or in those with increased abdominal pressure. In a given individual, the adequate mean arterial pressure target can be difficult to define with the routine hemodynamic parameters (for example, cardiac output, central or mixed venous blood oxygen saturation, and urine output). Near-infrared spectroscopy and sidestream dark field imaging have emerged as promising technologies for monitoring the microcirculation at the bedside. These new methods could provide additional clues to help define the adequate blood pressure to target during the resuscitation phase of septic shock. PMID- 22047946 TI - Clinical relevance of single nucleotide polymorphisms of the high mobility group box 1 protein gene in patients with major trauma in southwest China. AB - BACKGROUND: High-mobility group box protein 1 (HMGB1) is a pivotal late mediator involved in the development of sepsis and multiple organ dysfunction syndrome (MODS) in critically ill patients. While several single nucleotide polymorphisms (SNPs) have been demonstrated to be critical determinants for outcome of critically ill patients, little is known about the clinical relevance of SNPs of the HMGB1 gene up to date. METHODS: A total of 3 tag SNPs of the HMGB1 gene were selected using HapMap database and linkage disequilibrium analysis. The tag SNPs were genotyped using a pyrosequencing methodology in 556 unrelated patients with major trauma. Peripheral whole blood samples obtained immediately after admission were determined for HMGB1 production in response to ex vivo lipopolysaccharide (LPS) stimulation. RESULTS: The rs2249825 SNP and the haplotype TCG were significantly associated with LPS-induced HMGB1 production by peripheral blood leukocytes. There were also significant differences in sepsis morbidity rate and MOD scores among patients with different genotypes of the rs2249825. In addition, the patients with the wild-type haplotype TCG had a lesser sepsis morbidity rate and MOD scores than those without the TCG haplotype. CONCLUSION: A total of 3 SNPs might act as tag SNPs for the entire HMGB1 gene. The rs2249825 and the haplotype TCG might be used as relevant risk estimate for the development of sepsis and MODS in patients with major trauma. PMID- 22047947 TI - Evidence from auditory and visual event-related potential (ERP) studies of deviance detection (MMN and vMMN) linking predictive coding theories and perceptual object representations. AB - Predictive coding theories posit that the perceptual system is structured as a hierarchically organized set of generative models with increasingly general models at higher levels. The difference between model predictions and the actual input (prediction error) drives model selection and adaptation processes minimizing the prediction error. Event-related brain potentials elicited by sensory deviance are thought to reflect the processing of prediction error at an intermediate level in the hierarchy. We review evidence from auditory and visual studies of deviance detection suggesting that the memory representations inferred from these studies meet the criteria set for perceptual object representations. Based on this evidence we then argue that these perceptual object representations are closely related to the generative models assumed by predictive coding theories. PMID- 22047948 TI - Booster-effect with velaglucerase alfa in patients with Gaucher disease switched from long-term imiglucerase therapy: early Access Program results from Jerusalem. AB - BACKGROUND: Decreased spleen and liver volumes and increased hemoglobin levels and platelet counts usually occur with enzyme replacement therapy (ERT) in symptomatic patients with Gaucher disease. Because of decreased supply of imiglucerase, an FDA-approved Early Access Program (EAP) allowed use of a new, pre-licensed ERT, velaglucerase alfa. This report provides safety and efficacy findings in patients on EAP velaglucerase alfa who completed 6, 9, or 12 months as intravenous every-other-week ERT. METHOD: EAP was approved by the Israeli Ministry of Health. All patients enrolled in the EAP were included for safety measures; only those with >6 month evaluations of hemoglobin, platelet counts, and liver and spleen volumes were included for efficacy. Descriptive statistics were employed. RESULTS: Among 71 EAP patients, there were no drug-related serious adverse events or withdrawals; one patient (1.4%) with previous hypersensitivity to a different ERT had a drug-related allergic reaction. Of 44 patients with appropriate time-period evaluations, 8 patients were treatment-naive and responded well to velaglucerase alfa. The 36 switch-over patients remained at imiglucerase low-doses; a majority of patients showed improvements in each efficacy parameter. CONCLUSION: Switch-over from imiglucerase (10-224 months) was safe and in several patients velaglucerase alfa induced a booster-effect. PMID- 22047949 TI - [The stent is only one tool in the treatment of STEMI]. PMID- 22047950 TI - Players between the worlds: multifunctional DNA translocases. AB - DNA translocases play important roles during the bacterial cell cycle and in cell differentiation. Escherichia coli cells contain a multifunctional translocase, FtsK, which is involved in cell division, late steps of chromosome segregation and dimer resolution. In Gram-positive bacteria, the latter two processes are achieved by two translocases, SftA and SpoIIIE. These two translocases operate in a two step fashion, before and after closure of the division septum. DNA translocases have the remarkable ability to translocate DNA in a vectorial manner, orienting themselves according to polar sequences present in bacterial genomes, and perform various additional roles during the cell cycle. DNA translocases genetically interact with Structural Maintenance of Chromosomes (SMC) proteins in a flexible manner in different species, underlining the high versatility of this class of proteins. PMID- 22047951 TI - PGC-1 coactivators in the cardiovascular system. AB - The beating heart consumes more ATP per weight than any other organ. The machineries required for this are many and complex. Fuel and oxygen must be transported via the vasculature, absorbed by cardiomyocytes, broken down, and regulated to match cellular demands. Much of this occurs in mitochondria, which comprise fully one third of cardiac mass. The PGC-1 proteins are transcriptional coactivators that have emerged as powerful orchestrators of these numerous processes, ensuring their proper coregulation in response to intracellular and extracellular cues. An important role for PGC-1s in cardiac function has been revealed over the past few years, and more recently interest in their role in the vasculature has been burgeoning. We review this literature, focusing on recent developments. PMID- 22047953 TI - Respiratory distress in Pierre Robin sequence: an experience with mandible traction with wires - Baciliero et al./Int J Oral Maxilofac Surg 2011;40:464-470. PMID- 22047952 TI - Sex hormone-binding globulin and type 2 diabetes mellitus. AB - Sex hormone-binding globulin (SHBG) has emerged as one of the multiple genetic and environmental factors that potentially contribute to the pathophysiology of type 2 diabetes mellitus (T2DM). In addition to epidemiologic studies demonstrating a consistent relationship between decreased levels of serum SHBG and incident T2DM, recent genetic studies also reveal that transmission of specific polymorphisms in the SHBG gene influence the risk of T2DM. At the molecular level, the multiple interactions between SHBG and its receptors in various target tissues suggest physiologic roles for SHBG that are more complex than the simple transport of sex hormones in serum. Taken together, these data provide support for an expanded role of SHBG in the pathophysiology of insulin resistance and T2DM. PMID- 22047954 TI - Evaluation of an improved orthognathic articulator system. 2. Accuracy of occlusal wafers. AB - The errors produced by occlusal wafers constructed on casts of the teeth mounted on a standard articulator and an improved orthognathic articulator were investigated by carrying out simulated orthognathic surgery on plastic skulls. The wafers were used to relocate the position of the maxillae of the skulls. The vertical and horizontal displacements of the maxillae were determined from measurements of the positions of markers on the skull and teeth. Comparison of the magnitudes of the actual and intended movements showed that wafers constructed on the standard articulator had systematic prediction errors of up to 5mm, but the improved orthognathic articulator showed much smaller random errors. There was a statistically significant improvement in overall accuracy in predicting maxillary Le Fort I position with the use of the improved orthognathic articulator which the authors recommend for clinical use. PMID- 22047955 TI - Evaluation of an improved orthognathic articulator system: 1. Accuracy of cast orientation. AB - A systematic study was carried out using plastic model skulls to quantify the accuracy of the transfer of face bow registration to the articulator. A standard Dentatus semi-adjustable articulator system was compared to a purpose built orthognathic articulator system by measuring the maxillary occlusal plane angles of plastic model skulls and of dental casts mounted on the two different types of articulators. There was a statistically significant difference between the two systems; the orthognathic system showed small random errors, but the standard system showed systematic errors of up to 28 degrees . PMID- 22047956 TI - Effects of prolonged stress on salivary cortisol and dehydroepiandrosterone: a study of a two-week teaching practice. AB - This study investigated variations in salivary levels of cortisol and dehydroepiandrosterone (DHEA) in a prolonged stressful situation (a two-week teaching practice). Thirty-three women for whom a two-week teaching practice at a kindergarten was scheduled were asked to collect saliva samples at awakening, 30 min after awakening, and bedtime at four time points: two weeks before the practice, the first week of the practice, the second week of the practice, and a few days after the practice. In addition, they completed questionnaires for assessing perceived stress and subjective moods on each day. A linear mixed model indicated that cortisol levels significantly increased during the first and second week of the practice compared with those before and after the practice period, and that DHEA levels significantly decreased after the practice period compared with those at the other time points. Further, cortisol awakening response after the practice period significantly reduced compared with that at the other time points. Scores of perceived stress and negative moods were also higher during the practice period. This study showed that prolonged stress affected cortisol and DHEA secretion during as well as after the stress period. PMID- 22047957 TI - Morphine history sensitizes postsynaptic GABA receptors on dorsal raphe serotonin neurons in a stress-induced relapse model in rats. AB - The serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in stress-related psychiatric disorders and substance abuse. Previous work has shown that the dorsal raphe nucleus (DR)-5-HT system is inhibited by swim stress via stimulation of GABA synaptic activity by the stress neurohormone corticotropin releasing factor (CRF). Additionally, the DR 5-HT system is regulated by opioids. The present study tests the hypothesis that the DR 5-HT system regulates stress induced opioid relapse. In the first experiment, electrophysiological recordings of GABA synaptic activity in 5-HT DR neurons were conducted in brain slices from Sprague-Dawley rats that were exposed to swim stress-induced reinstatement of previously extinguished morphine conditioned place preference (CPP). Behavioral data indicate that swim stress triggers reinstatement of morphine CPP. Electrophysiology data indicate that 5-HT neurons in the morphine-conditioned group exposed to stress had increased amplitude of inhibitory postsynaptic currents (IPSCs), which would indicate greater postsynaptic GABA receptor density and/or sensitivity, compared to saline controls exposed to stress. In the second experiment, rats were exposed to either morphine or saline CPP and extinction, and then 5-HT DR neurons from both groups were examined for sensitivity to CRF in vitro. CRF induced a greater inward current in 5-HT neurons from morphine conditioned subjects compared to saline-conditioned subjects. These data indicate that morphine history sensitizes 5-HT DR neurons to the GABAergic inhibitory effects of stress as well as to some of the effects of CRF. These mechanisms may sensitize subjects with a morphine history to the dysphoric effects of stressors and ultimately confer an enhanced vulnerability to stress-induced opioid relapse. PMID- 22047958 TI - Early pospartum alexithymia and risk for depression: relationship with serum thyrotropin, free thyroid hormones and thyroid autoantibodies. AB - Most psychometric evaluations in the postpartum (PP) target depression (PPD) and show an association with thyroid autoantibodies (TAb), not with thyroid function. Three studies evaluated PP alexithymia, but none its relationship with thyroid indices. We tested 74 women aged 31.8+/-4.64 years, on day 3 PP, by the Edinburgh Postnatal Depression Scale (EPDS), the Montgomery and Asberg Depression Rating Scale (MADRS), and the Toronto Alexithymia Scale (TAS). Concurrently, we measured serum thyrotropin (TSH), free T3 (FT3), free T4 (FT4), thyroperoxidase and thyroglobulin antibodies (TPOAb, TgAb). Using cut-off scores of >=12 (EPDS), >=15 (MADRS) and >=61 (TAS), rates of women with abnormal EPDS and MADRS scores were similar (31%, 30% and 28.4%, respectively). TAS scores were higher and proportions of alexithymics were greater in the abnormal EPDS group or in the abnormal MADRS group than in the normal EPDS or MADRS group. EPDS correlated significantly with TAS. Compared to nonalexithymics, alexythimics had lower FT4, higher FT3, lower FT4:FT3 ratio, and insignificantly higher TPOAb or TgAb levels. Only TPOAb and TgAb were significantly higher in women at risk for PPD compared to women not at risk for PPD, but solely at EPDS cut-off values of >=13 or >=14. TAS correlated directly with TPOAb and FT3, and inversely with FT4:FT3 ratio, while EPDS correlated only with TPOAb. Comparing women at risk for depression but nonalexithymics or women alexithymics but not at risk for depression vs. women normal on all scales, the former had lower FT3 and higher FT4:FT3 ratio while the latter had lower both FT4 and FT4:FT3 ratio. We conclude that PPD risk and alexithymia (i) are partly comorbid and directly associated with thyroid autoimmunity; (ii) their association with serum free thyroid hormones and with FT4:FT3 ratio goes in opposite directions. PMID- 22047959 TI - Dexamethasone increases ROS production and T cell suppressive capacity by anti inflammatory macrophages. AB - Macrophages have been demonstrated to suppress T cell responses by producing reactive oxygen species (ROS) leading to the subsequent induction of T regulatory cells in a ROS-dependent manner. Macrophages may therefore be instrumental in downregulating T cell responses in situations of exacerbated immune responses. Here we investigated the effect of immunosuppressive drugs on ROS production by macrophage subsets and the subsequent effects on T cell activation. Macrophage types 1 and 2 were differentiated with GM-CSF or M-CSF, in presence or absence of dexamethasone, cyclosporine A, FK506, rapamycin, or mycophenolic acid. The ROS producing capacity of fully differentiated Mph was highest in anti-inflammatory Mph2 and not affected by exposure to immunosuppressive drugs. However, presence of rapamycin during Mph2 differentiation decreased the ROS production of these cells. In contrast, other immunosuppressive drugs, with dexamethasone being the most potent, increased the ROS producing capacity of Mph2. Intriguingly although the ROS producing ability of Mph1 was unaffected, dexamethasone strongly increased the ROS producing capabilities of dendritic cells. Both at the mRNA and protein level we found that dexamethasone enhanced the expression of NOX2 protein p47(phox). Functionally, dexamethasone further enhanced the capacity of Mph2 to suppress T cell mediated IFN-gamma and IL-4 production. In vivo, only in rats with normal ROS production (congenic DA.Ncf1(E3/E3)) it was observed that dexamethasone injection resulted in long-lasting upregulation of ROS production by macrophages and induced higher levels of Treg in a ROS-dependent manner. In conclusion, we show that the anti-inflammatory drug dexamethasone increases the ROS producing capacity of macrophages. PMID- 22047960 TI - Signaling pathway-based identification of extensive prognostic gene signatures for lung adenocarcinoma. AB - Tumor recurrence is the major cause of death in lung cancer treatment. To date, there is no clinically applied gene expression-based model to predict the risk for tumor recurrence in non-small cell lung cancer (NSCLC). We sought to embed crosstalk with major signaling pathways into biomarker identification. Three approaches were used to identify prognostic gene signatures from 442 lung adenocarcinoma samples. Candidate genes co-expressed with 6 or 7 major NSCLC signaling hallmarks were identified from genome-wide coexpression networks specifically associated with different prognostic groups. From these candidate genes, the first approach selected genes significantly associated with disease specific survival using univariate Cox model. The second approach used random forests to refine the gene signatures; and the third approach used Relief algorithm to form the final gene sets. A total of 21 gene signatures were identified using these three approaches. These gene signatures generated significant prognostic stratifications (log-rank P<0.05 in Kaplan-Meier analyses; hazard ratio >1, P<0.05) in all tumors, stage I only, and in stage I patients not receiving chemotherapy in all training and test sets. In multivariate analyses with age, gender, race, smoking history, cancer stage, and tumor differentiation, a 10-gene signature had a hazard ratio of 3.23 (95% CI: [1.48, 7.06]), which was a more significant prognostic factor than other clinical factors, except cancer stage (III vs. I; with no significant difference). All identified 21 gene signatures outperformed other lung cancer signatures evaluated in the Director's Challenge Study. This study is an important step toward personalized prognosis of tumor recurrence and patient selection for adjuvant chemotherapy, with significant impact on down-stream clinical applications. PMID- 22047961 TI - Frequent methylation and oncogenic role of microRNA-34b/c in small-cell lung cancer. AB - Small-cell lung cancer (SCLC) is an aggressive tumor with a dismal prognosis among primary lung cancers. MicroRNAs (miRNAs) can act as oncogenes or tumor suppressor genes in human malignancy. The miR-34 family is comprised of tumor suppressive miRNAs, and its reduced expression by methylation has been reported in various cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the alteration and tumor-suppressive impact of miR-34s in SCLC. The methylation of miR-34a and miR-34b/c was observed in 4 (36%) and 7 (64%) of 11 SCLC cell lines, respectively. Among the 27 SCLC clinical specimens, miR-34a and miR-34b/c were methylated in 4 (15%) and 18 (67%), respectively. In contrast, 13 (28%) miR-34a methylated cases and 12 (26%) miR-34b/c methylated cases were found in 47 NSCLC primary tumors. The frequency of miR-34b/c methylation was significantly higher in SCLC than in NSCLC (p<0.001). The expressions of miR-34s were reduced in methylated cell lines and tumors and restored after 5-aza-2' deoxycytidine treatment, indicating that methylation was responsible for the reduced expression of miR-34s. Because the frequency of methylation was higher in miR-34b/c, we focused on miR-34b/c for a functional analysis. We examined the effect of miR-34b/c introduction on cell proliferation, migration and invasion. The transfection of miR-34b/c to two SCLC cell lines (H1048 and SBC5) resulted in the significant inhibition of cell growth, migration, and invasion, compared with control transfectants. Our results indicate that the aberrant methylation of miR 34b/c plays an important role in the pathogenesis of SCLC, implying that miR 34b/c may be a useful therapeutic target for SCLC. PMID- 22047962 TI - [A "checklist" for the implantation of central venous catheters and vascular access implantable devices in nephrology: why?]. AB - The French Health Agency (HAS), published recently a check-list for central venous catheter. The document is published for transmission to French nephrologists. PMID- 22047964 TI - Attention reverses the effect of prediction in silencing sensory signals. AB - Predictive coding models suggest that predicted sensory signals are attenuated (silencing of prediction error). These models, though influential, are challenged by the fact that prediction sometimes seems to enhance rather than reduce sensory signals, as in the case of attentional cueing experiments. One possible explanation is that in these experiments, prediction (i.e., stimulus probability) is confounded with attention (i.e., task relevance), which is known to boost rather than reduce sensory signal. However, recent theoretical work on predictive coding inspires an alternative hypothesis and suggests that attention and prediction operate synergistically to improve the precision of perceptual inference. This model posits that attention leads to heightened weighting of sensory evidence, thereby reversing the sensory silencing by prediction. Here, we factorially manipulated attention and prediction in a functional magnetic resonance imaging study and distinguished between these 2 hypotheses. Our results support a predictive coding model wherein attention reverses the sensory attenuation of predicted signals. PMID- 22047963 TI - Parcellations and hemispheric asymmetries of human cerebral cortex analyzed on surface-based atlases. AB - We report on surface-based analyses that enhance our understanding of human cortical organization, including its convolutions and its parcellation into many distinct areas. The surface area of human neocortex averages 973 cm(2) per hemisphere, based on cortical midthickness surfaces of 2 cohorts of subjects. We implemented a method to register individual subjects to a hybrid version of the FreeSurfer "fsaverage" atlas whose left and right hemispheres are in precise geographic correspondence. Cortical folding patterns in the resultant population average "fs_LR" midthickness surfaces are remarkably similar in the left and right hemispheres, even in regions showing significant asymmetry in 3D position. Both hemispheres are equal in average surface area, but hotspots of surface area asymmetry are present in the Sylvian Fissure and elsewhere, together with a broad pattern of asymmetries that are significant though small in magnitude. Multiple cortical parcellation schemes registered to the human atlas provide valuable reference data sets for comparisons with other studies. Identified cortical areas vary in size by more than 2 orders of magnitude. The total number of human neocortical areas is estimated to be ~150 to 200 areas per hemisphere, which is modestly larger than a recent estimate for the macaque. PMID- 22047965 TI - Loss of visually driven synaptic responses in layer 4 regular-spiking neurons of rat visual cortex in absence of competing inputs. AB - Monocular deprivation (MD) during development shifts the ocular preference of primary visual cortex (V1) neurons by depressing closed-eye responses and potentiating open-eye responses. As these 2 processes are temporally and mechanistically distinct, we tested whether loss of responsiveness occurs also in absence of competing inputs. We thus compared the effects of long-term MD in layer 4 regular-spiking pyramidal neurons (L4Ns) of binocular and monocular V1 (bV1 and mV1) with whole-cell recordings. In bV1, input depression was larger than potentiation, and the ocular dominance shift was larger for spike outputs. MD-but not retinal inactivation with tetrodotoxin-caused a comparable loss of synaptic and spike responsiveness in mV1, which is innervated only by the deprived eye. Conversely, brief MD depressed synaptic responses only in bV1. MD driven depression in mV1 was accompanied by a proportional reduction of visual thalamic inputs, as assessed upon pharmacological silencing of intracortical transmission. Finally, sub- and suprathreshold responsiveness was similarly degraded in L4Ns of bV1 upon complete deprivation of patterned vision through a binocular deprivation period of comparable length. Thus, loss of synaptic inputs from the deprived eye occurs also in absence of competition in the main thalamorecipient lamina, albeit at a slower pace. PMID- 22047967 TI - Distinct neural substrates for semantic knowledge and naming in the temporoparietal network. AB - Patients with anterior temporal lobe (ATL) lesions show semantic and lexical retrieval deficits, and the differential role of this area in the 2 processes is debated. Functional neuroimaging in healthy individuals has not clarified the matter because semantic and lexical processes usually occur simultaneously and automatically. Furthermore, the ATL is a region challenging for functional magnetic resonance imaging (fMRI) due to susceptibility artifacts, especially at high fields. In this study, we established an optimized ATL-sensitive fMRI acquisition protocol at 4 T and applied an event-related paradigm to study the identification (i.e., association of semantic biographical information) of celebrities, with and without the ability to retrieve their proper names. While semantic processing reliably activated the ATL, only more posterior areas in the left temporal and temporal-parietal junction were significantly modulated by covert lexical retrieval. These results suggest that within a temporoparietal network, the ATL is relatively more important for semantic processing, and posterior language regions are relatively more important for lexical retrieval. PMID- 22047968 TI - Is there a common neuroanatomical substrate of language deficit between autism spectrum disorder and specific language impairment? AB - Discussion of an overlap between specific language impairment (SLI) and autism spectrum disorder (ASD) is on going. The most intriguing overlap between both phenotypes is the similarity in the observed language deficits described in SLI and a subgroup of ASD with co-occurring linguistic impairment, ASD-LI. Examining whether a similar neuroanatomical substrate underlies this phenotypical linguistic overlap, we studied the white matter microstructural properties of the superior longitudinal fascicle (SLF) of 19 ASD-LI adolescents (mean age 13.8 +/- 1.6 years) and 21 age-matched controls and compared them with 13 SLI children (mean age 10.1 +/- 0.4 years) and 12 age-matched controls. A linguistic profile assessment and a diffusion tensor imaging analysis of the SLF were performed. Linguistic testing revealed a mixed receptive-expressive disorder profile in both groups, confirming their overlap at phenotypical level. At neuroanatomical level, no significant differences in mean SLF fractional anisotropy (FA) and mean SLF apparent diffusion coefficient values between ASD-LI participants and controls were seen. By contrast, the mean SLF FA was significantly reduced in the SLI children as compared with their controls. The observation of structural SLF disturbances in SLI but not in ASD-LI suggests the existence of a different neuroanatomical substrate for the language deficits in both disorders. PMID- 22047966 TI - Effect of dopamine transporter genotype on intrinsic functional connectivity depends on cognitive state. AB - Functional connectivity between brain regions can define large-scale neural networks and provide information about relationships between those networks. We examined how relationships within and across intrinsic connectivity networks were 1) sensitive to individual differences in dopaminergic function, 2) modulated by cognitive state, and 3) associated with executive behavioral traits. We found that regardless of cognitive state, connections between frontal, parietal, and striatal nodes of Task-Positive networks (TPNs) and Task-Negative networks (TNNs) showed higher functional connectivity in 10/10 homozygotes of the dopamine transporter gene, a polymorphism influencing synaptic dopamine, than in 9/10 heterozygotes. However, performance of a working memory task (a state requiring dopamine release) modulated genotype differences selectively, such that cross network connectivity between TPNs and TNNs was higher in 10/10 than 9/10 subjects during working memory but not during rest. This increased cross-network connectivity was associated with increased self-reported measures of impulsivity and inattention traits. By linking a gene regulating synaptic dopamine to a phenotype characterized by inefficient executive function, these findings validate cross-network connectivity as an endophenotype of executive dysfunction. PMID- 22047969 TI - A computational growth model for measuring dynamic cortical development in the first year of life. AB - Human cerebral cortex develops extremely fast in the first year of life. Quantitative measurement of cortical development during this early stage plays an important role in revealing the relationship between cortical structural and high level functional development. This paper presents a computational growth model to simulate the dynamic development of the cerebral cortex from birth to 1 year old by modeling the cerebral cortex as a deformable elastoplasticity surface driven via a growth model. To achieve a high accuracy, a guidance model is also incorporated to estimate the growth parameters and cortical shapes at later developmental stages. The proposed growth model has been applied to 10 healthy subjects with longitudinal brain MR images acquired at every 3 months from birth to 1 year old. The experimental results show that our proposed method can capture the dynamic developmental process of the cortex, with the average surface distance error smaller than 0.6 mm compared with the ground truth surfaces, and the results also show that 1) the curvedness and sharpness decrease from 2 weeks to 12 months and 2) the frontal lobe shows rapidly increasing cortical folding during this period, with relatively slower increase of the cortical folding in the occipital and parietal lobes. PMID- 22047970 TI - Multiple sclerosis-quenching the flames of inflammation. PMID- 22047971 TI - Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. AB - BACKGROUND: B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing remitting multiple sclerosis. METHODS: We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 MUg) once a week. The randomisation list was not disclosed to the study centres, monitors, project statisticians or to the project team at Roche. All groups were double blinded to group assignment, except the interferon beta-1a group who were rater masked. At week 24, patients in the initial placebo, 600 mg ocrelizumab, and interferon beta-1a groups received ocrelizumab 600 mg; the 2000 mg group received 1000 mg. Our primary endpoint was the total number of gadolinium-enhancing lesions (GEL) and T1-weighted MRI at weeks 12, 16, 20, and 24. Analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00676715. FINDINGS: 218 (99%) of the 220 randomised patients received at least one dose of ocrelizumab, 204 (93%) completed 24 weeks of the study and 196 (89%) completed 48 weeks. In the intention-to-treat population of 218 patients, at week 24, the number of gadolinium-enhancing lesions was 89% (95% CI 68-97; p<0.0001) lower in the 600 mg ocrelizumab group than in the placebo group, and 96% (89-99; p<0.0001) lower in the 2000 mg group. In exploratory analyses, both 600 mg and 2000 mg ocrelizumab groups were better than interferon beta-1a for GEL reduction. We noted serious adverse events in two of 54 (4%; 95% CI 3.0 4.4) patients in the placebo group, one of 55 (2%; 1.3-2.3) in the 600 mg ocrelizumab group, three of 55 (5%; 4.6-6.3) in the 2000 mg group, and two of 54 (4%; 3.0-4.4) in the interferon beta-1a group. INTERPRETATION: The similarly pronounced effects of B-cell depletion with both ocrelizumab doses on MRI and relapse-related outcomes support a role for B-cells in disease pathogenesis and warrant further assessment in large, long-term trials. FUNDING: F Hoffmann-La Roche Ltd, Biogen Idec Inc. PMID- 22047972 TI - Both adiponectin and interleukin-10 inhibit LPS-induced activation of the NF kappaB pathway in 3T3-L1 adipocytes. AB - Adiponectin and interleukin 10 (IL-10) are adipokines that are predominantly secreted by differentiated adipocytes and are involved in energy homeostasis, insulin sensitivity, and the anti-inflammatory response. These two adipokines are reduced in obese subjects, which favors increased activation of nuclear factor kappa B (NF-kappaB) and leads to elevation of pro-inflammatory adipokines. However, the effects of adiponectin and IL-10 on NF-kappaB DNA binding activity (NF-kappaBp50 and NF-kappaBp65) and proteins involved with the toll-like receptor (TLR-2 and TLR-4) pathway, such as MYD88 and TRAF6 expression, in lipopolysaccharide-treated 3T3-L1 adipocytes are unknown. Stimulation of lipopolysaccharide-treated 3T3-L1 adipocytes for 24h elevated IL-6 levels; activated the NF-kappaB pathway cascade; increased protein expression of IL-6R, TLR-4, MYD88, and TRAF6; and increased the nuclear activity of NF-kappaB (p50 and p65) DNA binding. Adiponectin and IL-10 inhibited the elevation of IL-6 levels and activated NF-kappaB (p50 and p65) DNA binding. Taken together, the present results provide evidence that adiponectin and IL-10 have an important role in the anti-inflammatory response in adipocytes. In addition, inhibition of NF-kappaB signaling pathways may be an excellent strategy for the treatment of inflammation in obese individuals. PMID- 22047973 TI - Ultrasensitive indicator-free and enhanced self-signal nanohybrid DNA sensing platform based on electrochemically grown poly-xanthurenic acid/Fe2O3 membranes. AB - This paper describes a novel electrochemical DNA biosensor for simple, rapid, and specific detection of PML/RARA fusion gene in acute promyelocytic leukemia by using 18-mer single-stranded deoxyribonucleic acid as the capture probe. Nanosized Fe(2)O(3) was first immobilized on the surface of a carbon paste electrode (CPE). Then poly-xanthurenic acid (PXa), a new electroactive material, was electrogenerated by using the pulse potentiostatic method on the Fe(2)O(3) substrate to form a unique and uniform nanorhombus structure. Due to the unique binding ability of xanthurenic acid (Xa) with Fe(2)O(3), Xa monomers tended to be adsorbed around nanosized Fe(2)O(3), and the electropolymerization efficiency was greatly improved. Owing to the presence of abundant carboxyl groups, the capture probe was covalently attached on the carboxyl-terminated PXa/Fe(2)O(3) nanorhombus membranes through the free amines of DNA sequences based on the 1 ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydrosulfosuccinimide cross linking reaction. The covalently immobilized capture probe could selectively hybridize with its target DNA to form double-stranded DNA on the PXa/Fe(2)O(3)/CPE surface. Electrochemical impedance spectroscopy was adopted for indicator-free monitoring of the hybridization reaction on the probe-captured electrode. As a result, the efficient probe immobilization platform, coupled with the ultrasensitive indicator-free impedance measurement, gave rise to a detection limit of 2.8 fmol/L and a dynamic range spanning 8 orders of magnitude. The excellent analytical properties of the proposed biosensor developed here holds great promise for ultrasensitive detection of other biorecognition events and diagnosis of diseases in practice. PMID- 22047974 TI - Temperature scans/cycles for the detection of low abundant DNA point mutations on microarrays. AB - The possibility to detect low abundant DNA point mutations is essential for early cancer diagnosis and/or prognosis. Furthermore, in order to be less invasive, the somatic mutations are not only sought in tumor extract samples but also from body fluids or stools rendering their content even more diluted compared to the wild type sequences. In this short communication, we propose two protocols based on temperature scans or cycles for the enrichment of the mutation strands hybridized on microarrays. We predict numerically and confirm experimentally a 10-fold increase in the fraction of mutated DNA hybridized on the microarray compared to the sample content. Coupled to more standard solution phase enrichment techniques, it would be possible to lower by one order of magnitude the current detection limit with the advantage of multiple mutation detections offered by the microarray technology. PMID- 22047975 TI - A novel structural specific creatinine sensing scheme for the determination of the urine creatinine. AB - In this work, a highly structural dependent amperometric scheme was proposed for the determination of creatinine without enzymatic assistance. The principle of this novel method is based upon the formation of a soluble copper-creatinine complex on the copper electrode surface. Subsequently, an oxidative current from the regeneration of the surface oxide layer is monitored and it is proportional to the concentration of the creatinine. This scheme can be conducted at potential of -0.1 V (vs. Ag/AgCl, 3 M) in phosphate buffer (pH 7). A typical calibration plot from 25 MUg/dL to 1.5 mg/dL (R(2)=0.997) with a detection limit of 6.8 MUg/dL (S/N=3) is achieved. The relative standard deviation of 21 successive injections of 0.2 mg/dL creatinine is 0.018. Under the optimal conditions, the frequently encountered biological interferences at physiological or higher concentration were investigated. Only uric acid revealed an obvious interference (298.1%). However, a Nafion((r)) coated copper plating electrode shows a successful decrement of the interference of the uric acid with slightly decreased sensitivity of creatinine. The feasibility of this scheme for further clinical application is demonstrated by both HPLC and FIA to evaluate the creatinine concentration in a urine sample. PMID- 22047977 TI - Co-morbidities as predictors of mortality in Clostridium difficile infection and derivation of the ARC predictive score. AB - Clostridium difficile associated diarrhoea (CDAD) has increased significantly in the last 15 years, but predictors of outcome are inadequately understood. This was a cohort study of 2761 patients in North East England between 2002 and 2009, with the end-point of mortality at 30 days. The role of age, gender and co morbidities was examined by binary logistic regression. Rounded odds ratios were used to develop a predictive score. A predictive score based on age, renal disease and cancer (ARC score) differentiated groups with differing risk of 30 day mortality (risk for score of 0-3 was 9-21%, score of 4-7 was 31-48% and score of 8 was 66%). Co-morbidities were shown to be important predictors of outcome in CDAD, and can be combined with age in the ARC score to assess the likelihood of survival. This requires further validation in other populations, but has important implications for clinical and research practice. PMID- 22047976 TI - Increased intra-individual reaction time variability in cocaine-dependent subjects: role of cocaine-related cues. AB - Neuroimaging data suggest that impaired performance on response inhibition and information processing tests in cocaine-dependent subjects is related to prefrontal and frontal cortical dysfunction and that dysfunction in these brain areas may underlie some aspects of cocaine addiction. In subjects with attention deficit hyperactivity disorder and other psychiatric disorders, the Intra Individual Reaction Time Variability (IIRTV) has been associated with frontal cortical dysfunction. In the present study, we evaluated IIRTV parameters in cocaine-dependent subjects vs. controls using a cocaine Stroop task. Fifty control and 123 cocaine-dependent subjects compiled from three studies completed a cocaine Stroop task. Standard deviation (SD) and coefficient of variation (CV) for reaction times (RT) were calculated for both trials with neutral and trials with cocaine-related words. The parameters mu, sigma, and tau were calculated using an ex-Gaussian analysis employed to characterize variability in RTs. The ex Gaussian analysis divides the RTs into normal (mu, sigma) and exponential (tau) components. Using robust regression analysis, cocaine-dependent subjects showed greater SD, CV and Tau on trials with cocaine-related words compared to controls (p<0.05). However, in trials with neutral words, there was no evidence of group differences in any IIRTV parameters (p>0.05). The Wilcoxon matched-pairs signed rank test showed that for cocaine-dependent subjects, both SD and tau were larger in trials with cocaine-related words than in trials with neutral words (p<0.05). The observation that only cocaine-related words increased IIRTV in cocaine dependent subjects suggests that cocaine-related stimuli might disrupt information processing subserved by prefrontal and frontal cortical circuits. PMID- 22047978 TI - Ultrasound screening of periarticular soft tissue abnormality around metal-on metal bearings. AB - Although metal hypersensitivity or pseudotumors are concerns for metal-on-metal (MoM) bearings, detailed pathologies of patterns, severity, and incidence of periprosthetic soft tissue lesions are incompletely understood. We examined the potential of ultrasound for screening of periarticular soft tissue lesions around MoM bearings. Ultrasound examinations were conducted in 88 hips (79 patients) with MoM hip resurfacings or MoM total hip arthroplasties with a large femoral head. Four qualitative ultrasound patterns were shown, including normal pattern in 69 hips, joint-expansion pattern in 11 hips, cystic pattern in 5 hips, and mass pattern in 3 hips. Hips with the latter 3 abnormal patterns showed significantly higher frequency of clinical symptoms, without significant differences of sex, duration of implantation, head sizes, and cup abduction/anteversion angles, compared with hips with normal pattern. Ultrasound examination provides sensitive screening of soft tissue reactions around MoM bearings and may be useful in monitoring progression and defining treatment for periarticular soft tissue abnormalities. PMID- 22047979 TI - Laparoscopic sleeve gastrectomy is the right terminology. PMID- 22047980 TI - How to use the bariatric analysis and reporting outcome system. PMID- 22047981 TI - Posttraumatic mossy fiber sprouting is related to the degree of cortical damage in three mouse strains. AB - Controlled cortical impact injury was used to examine relationships between focal posttraumatic cortical damage and mossy fiber sprouting (MFS) in the dentate gyrus in three mouse strains. Posttraumatic MFS was more robust when cortical injury impinged upon the hippocampus, versus contusions restricted to neocortex, and was qualitatively similar among CD-1, C57BL/6, and FVB/N background strains. Impact parameters influencing injury severity may be critical in reproducing epilepsy-related changes in neurotrauma models. PMID- 22047982 TI - Four novel and two recurrent NHLRC1 (EPM2B) and EPM2A gene mutations leading to Lafora disease in six Turkish families. AB - Lafora disease (LD) is a type of autosomal recessive, progressive myoclonus epilepsy resulting mostly from mutations in the EPM2A and NHLRC1 genes. Mutational analysis in both genes was initiated with the aim of establishing LD DNA diagnosis in Turkey. Four novel NHLRC1 (p.G131X, p.P69S and p.D82H) and EPM2A (p.V7A) and two recurrent NHLRC1 (p.D146N) and EPM2A (p.R241X) mutations were identified in six families. The delineation of causative mutations in patients provided early disease diagnosis for other family members and contributed to the knowledge of LD pathogenesis. PMID- 22047983 TI - Impact of mitral regurgitation on reverse remodeling and outcome in patients undergoing cardiac resynchronization therapy. AB - BACKGROUND: Mitral regurgitation (MR) is associated with reduced survival in patients with chronic heart failure, but may be improved with cardiac resynchronization therapy (CRT). We sought to evaluate the relationship between serial measurements of functional MR and reverse remodeling and outcomes in patients undergoing CRT. METHODS AND RESULTS: A total of 266 consecutive patients undergoing CRT with available baseline echocardiograms and subsequent clinical and echocardiographic follow-up were included in the analysis. Long-term follow up included all-cause mortality, heart transplantation, and implantation of a left ventricular (LV) assist device. Temporal changes in MR severity and LV end systolic volume index (LVESVi) were evaluated by linear mixed-model analysis. CRT led to an immediate sustained decrease in MR (P<0.0001), with no significant subsequent change. The amount of MR decrease correlated with a greater decrease in LVESVi late (P<=0.0001), but not early (P=0.14), after CRT began. Patients with severe MR before CRT experienced a larger LVESVi decrease (P=0.005). Although baseline MR severity was not associated with adverse events (P=0.13), a larger MR decrease (P=0.001) and a smaller residual MR after the initial 6 months of CRT (P=0.03) were predictive of better outcome in a multivariable model. CONCLUSIONS: Early reversal of functional MR was associated with reverse cardiac remodeling and improved outcomes. Patients with moderately severe to severe MR before CRT experienced relatively more reverse remodeling than patients with lesser degrees of MR. PMID- 22047984 TI - Estrogen replacement therapy for idiopathic outflow tract ventricular arrhythmias: a potential therapeutic approach. AB - Idiopathic outflow tract ventricular arrhythmias (IOTVA), including left and right ventricular outflow tract, are dued to cyclic adenosine monophosphate (cAMP)-mediated calcium-dependent delayed after depolarizations. A growing body of evidence suggests that the changes of sex hormone levels and gender differences may affect ventricular repolarization and be associated with the occurrence of ventricular arrhythmias. Recent studies showed that the level of estradiol in the IOTVA male patients decreased significantly and the count of ventricular arrhythmias was significantly negatively correlated with the level of estradiol in male patients with IOTVA. Meanwhile, estrogen replacement therapy could inhibit significantly the count of ventricular arrhythmias in the postmenopausal patients with IOTVA. In conclusion, estrogen replacement therapy may be a potential therapeutic approach for IOTVA besides postmenopausal patients. PMID- 22047985 TI - A common cause for a common phenotype: the gatekeeper hypothesis in fetal programming. AB - Sub-optimal nutrition during pregnancy has been shown to have long-term effects on the health of offspring in both humans and animals. The most common outcomes of such programming are hypertension, obesity, dyslipidaemia and insulin resistance. This spectrum of disorders, collectively known as metabolic syndrome, appears to be the consequence of nutritional insult during early development, irrespective of the nutritional stress experienced. For example, diets low in protein diet, high in fat, or deficient in iron are all associated with programming of cardiovascular and metabolic disorders when fed during rat pregnancy. In this paper, we hypothesise that the nutritional stresses act on genes or gene pathways common to all of the insults. We have termed these genes and/or gene pathways the "gatekeepers" and hence developed the "gatekeeper hypothesis". In this paper, we examine the background to the hypothesis and postulate some possible mechanisms or pathways that may constitute programming gatekeepers. PMID- 22047986 TI - Inhibition of translation initiation factors might be the potential therapeutic targets for HCV patients with hepatic iron overload. AB - Standard therapy, interferon-alpha (IFN-alpha) and ribavirin, remains the only available option for treatment of patients with hepatitis C virus (HCV) infection. However, iron overload, a common finding among HCV patients, have a poor response to treatment with current therapy. These data suggest that both host and viral factors are involved in the determination of the outcome of the therapy. Currently, novel antiviral compounds focus on the development of indirect antiviral drugs. The process of the viral translation is considered as the potential therapeutic targets. Coincidentally, study has found that hepatic iron load enhances the levels of eukaryotic initiation factor 3 (eIF3), which is essential for HCV translation. Reversely, iron chelation could reduce eIF3 p170 translation. Our hypothesis is that iron overload may specifically enhance cellular eIFs. As a result, the cellular mechanisms, in patients with iron overload, are utilized for translating viral mRNA into protein. Thus, treatment strategies that target eIFs should be an exceptionally good candidate therapeutic method for HCV patients with hepatic iron overload. PMID- 22047987 TI - Neuroprotective potential beyond immunoregulation of helminth infection as a therapeutic target in multiple sclerosis. AB - Multiple sclerosis (MS) is a common disabling autoimmune disease in young adults which does not have an effective treatment. The prevalence of immune-mediated diseases is higher in developed countries with hygienic environments, suggesting that helminthic infection may protect from autoimmune diseases. Previously, we reported that soluble egg antigens (SEA) from Schistosoma japonicum suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of MS, through up-regulating T helper-2 (Th2) immune responses in both the peripheral and central target organs. Neurotrophins (NTs) are not exclusive to the nervous system. While immune cells, especially Th2 cells, can produce and secrete a variety of NTs resulting in neuroprotective immunity. NTs can also modulate immune responses by augmenting Th2 responses and downregulating Th1 responses. Interestingly, nerve growth factor (NGF) has been found in liver granulomas of Schistosoma mansoni-infected mice. Moreover, in the central nervous system of chronic schistosomiasis, NGF is increased. A hypothesis is hereby proposed - SEA derived from S. japonicum bears neuroprotective properties beyond its immunomodulatory effects. SEA can induce the expression of NTs, which in turn augment Th2 immune responses induced by SEA; whereby a positive regulatory circuit between Th2 responses and NTs comes into being. PMID- 22047988 TI - The role of cyclo-oxygenase inhibitors in attenuating opioid-induced tolerance, hyperalgesia, and dependence. AB - There is no denying that opioids are the most important analgesic drugs which are widely used in clinical situations. Still, prolonged administration of these drugs can cause to reduce their analgesic efficacy due to the development of tolerance. These drugs can also cause induction of hyperalgesia. In addition, long-term administration of opioids through reinforcing- and rewarding pathways of limbic system can result in expression of opioid dependence with the unintended consequences of opioid abuse/misuse and finally opioid addiction. As studies show, over-activity in cyclo-oxygenase pathways and production of prostaglandins due to long-term exposures of opioid have a critical role in the development of tolerance to antinociceptive effect of opioid, hyperalgesia, and opioid dependence. The present study aims at suggesting the hypothesis that through blending a non-steroid anti-inflammatory drug with opioid actively causes reduction in unwanted effects of opioid i.e. by inhibition of opioid-induced cyclo-oxygenase overactivity whereas it is well-known that the combination therapy via reducing opioid dosage reduces the unwanted effects. PMID- 22047989 TI - The evolution of human immunodeficiency virus type-1 (HIV-1) envelope molecular properties and coreceptor use at all stages of infection in an HIV-1 donor recipient pair. AB - To trace the evolutionary patterns underlying evolution of coreceptor use within a host, we studied an HIV-1 transmission pair involving a donor who exclusively harbored CCR5-using (R5) variants throughout his entire disease course and a recipient who developed CXCR4-using variants. Over time, R5 variants in the donor optimized coreceptor use, which was associated with an increased number of potential N-linked glycosylation sites (PNGS) and elevated V3 charge in the viral envelope. Interestingly, R5 variants that were transmitted to the recipient preserved the viral characteristics of this late stage genotype and phenotype. Following a selective sweep, CXCR4-using variants subsequently emerged in the recipient coinciding with a further increase in the number of PNGS and V3 charge in the envelope of R5 viruses. Although described in a single transmission pair, the transmission and subsequent persistence of R5 variants with late stage characteristics demonstrate the potential for coreceptor use adaptation at the population level. PMID- 22047990 TI - Bradykinin enhances Sindbis virus infection in human brain microvascular endothelial cells. AB - Sindbis virus (SINV) induces inflammatory and vasoactive responses that are associated with rash and arthritis in human infections. The mechanisms underlying infection-associated microvasculopathy are still unknown. We investigated whether endothelial cells infected by SINV are differentially responsive to bradykinin (BK), a potent inducer of inflammatory edema in a broad range of infectious diseases. Human endothelial cells (HBMECs) infected with SINV presented an upregulation of bradykinin B2 receptors (BK2R) expression. Also, BK reduced SINV induced apoptosis and enhanced virus replication in HBMECs in a way dependent on BK2R, PI3 kinase and ERK signaling. Strikingly, intracerebral infection of mice in the presence of a BK2R antagonist reduced the local viral load. Our data suggest that SINV infection renders human endothelial cells hypersensitive to BK, which increases host cell survival and viral replication. Ongoing studies may clarify if the deregulation of the kinin pathway contributes to infection associated vasculopathies in life-threatening arbovirus infections. PMID- 22047991 TI - Heavy crude oils/particle stabilized emulsions. AB - Fluid characterization is a key technology for success in process design for crude oil mixtures in the future offshore. In the present article modern methods have been developed and optimized for crude oil applications. The focus is on destabilization processes in w/o emulsions, such as creaming/sedimentation and flocculation/coalescence. In our work, the separation technology was based on improvement of current devices to promote coalescence of the emulsified systems. Stabilizing properties based on particles was given special attention. A variety of particles like silica nanoparticles (AEROSIL(r)), asphalthenes, wax (paraffin) were used. The behavior of these particles and corresponding emulsion systems was determined by use of modern analytical equipment, such as SARA fractionation, NIR, electro-coalescers (determine critical electric field), Langmuir technique, pedant drop technique, TG-QCM, AFM. PMID- 22047992 TI - Correcting slice selectivity in hard pulse sequences. AB - Many MRI sequences use non-selective hard pulse excitation in the presence of imaging gradients. In this work, we investigate to which extent the sinc-shaped frequency excitation profiles of the pulse can be used for imaging without the generation of artefacts. A correction algorithm is proposed that eliminates the influence of the excitation profile. Phantom as well as in vivo measurements prove that enhanced image quality can be obtained as long as the first minimum of the excitation profile lies outside the imaged object. PMID- 22047993 TI - Solvent effect on the absorption and fluorescence of ergone: determination of ground and excited state dipole moments. AB - The effect of solvents on the absorption and emission spectra of ergone has been studied in various solvents at 298 K. The bathochromic shift was observed in absorption and fluorescence spectra with the increase of solvents polarity, which implied that transition involved was pi->pi*. And the normalized transition energy value E(T)(N) showed some scattering when plotted versus Deltanu. The ground state and excited state dipole moments were calculated by quantum mechanical second-order perturbation method as a function of the dielectric constant (epsilon) and refractive index (n). The result was found to be 1.435 D and 2.520 D in ground state and excited state respectively. And also, the density functional calculations were used to obtain the ground state and excited state dipole moments for it has proven to be suitable for calculating electronic excitation energy. And the result is consistent with the experimental. PMID- 22047995 TI - Maintained functionality of an implantable radiotelemetric blood pressure and heart rate sensor after magnetic resonance imaging in rats. AB - Radiotelemetric sensors for in vivo assessment of blood pressure and heart rate are widely used in animal research. MRI with implanted sensors is regarded as contraindicated as transmitter malfunction and injury of the animal may be caused. Moreover, artefacts are expected to compromise image evaluation. In vitro, the function of a radiotelemetric sensor (TA11PA-C10, Data Sciences International) after exposure to MRI up to 9.4 T was assessed. The magnetic force of the electromagnetic field on the sensor as well as radiofrequency (RF)-induced sensor heating was analysed. Finally, MRI with an implanted sensor was performed in a rat. Imaging artefacts were analysed at 3.0 and 9.4 T ex vivo and in vivo. Transmitted 24 h blood pressure and heart rate were compared before and after MRI to verify the integrity of the telemetric sensor. The function of the sensor was not altered by MRI up to 9.4 T. The maximum force exerted on the sensor was 273 +/- 50 mN. RF-induced heating was ruled out. Artefacts impeded the assessment of the abdomen and thorax in a dead rat, but not of the head and neck. MRI with implanted radiotelemetric sensors is feasible in principal. The tested sensor maintains functionality up to 9.4 T. Artefacts hampered abdominal and throacic imaging in rats, while assessment of the head and neck is possible. PMID- 22047996 TI - Liver X receptor agonist T0901317 induced liver perturbation in zebrafish: histological, gene set enrichment and expression analyses. AB - BACKGROUND: Liver X receptor (LXR), a ligand-activated transcription factor, regulates important biological processes. It has been associated with pathology and proposed as a therapeutic target. The zebrafish is a new vertebrate model for disease modeling, drug and toxicity screening and will be interesting to test for its potential for LXR-related studies. METHODS: Adult male fish were exposed to LXR agonist T0901317 at 20, 200 and 2000nM for 96h and the livers were sampled for histological, microarray and qRT-PCR analyses. RESULTS: Histological analysis suggests dose-dependent perturbation of carbohydrate and lipid metabolisms by T0901317 in the liver, which lead to hepatocyte swelling and cell death. Microarray data revealed several conserved effects of T0901317 with mammalian models, including up-regulation of LXR-targeted genes, modulation of biological pathways associated with proteasome, cell death, extracellular matrix and adhesions, maturity onset diabetes of the young and lipid beta oxidation. Interestingly, this study identified the complement and coagulation systems as down-regulated by T0901317 for the first time, potentially via transcriptional repression by LXR activation. qRT-PCR validated the expression of 16 representative genes, confirming activation of LXR signaling and down-regulation of these biological pathways by T0901317 which could be linked to the anti thrombogenic, anti-atherogenic and anti-inflammatory actions, as well as metabolic disruptions via LXR activation. CONCLUSION AND GENERAL SIGNIFICANCE: Our study underscores the potential of using zebrafish model coupled with transcriptomic analysis to capture pharmacological and toxicological or pathological events induced by LXR modulators. PMID- 22047997 TI - Nurse-directed interventions to reduce catheter-associated urinary tract infections. AB - BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are common, morbid, and costly. Nearly 25% of hospitalized patients are catheterized yearly, and 10% develop urinary tract infections. Evidence-based guidelines exist for indwelling urinary catheter management but are not consistently followed. METHODS: A pre/post intervention design was used in this quality improvement project to test the impact of nurse-driven interventions based on current evidence to reduce CAUTIs in hospitalized patients on 2 medical/surgical units. Interventions consisted of hospital-wide strategies including policy and product improvements and unit-specific strategies that focused on a review of current evidence to guide practice. RESULTS: The number of catheter days decreased from 3.01 to 2.2 (P = .018) on the surgery unit and from 3.53 to 2.7 (P = .076) on the medical unit. CAUTI rates were too low to achieve significant reduction. Product cost savings were estimated at $52,000/year. CONCLUSION: Guidelines derived from research and other sources of evidence can successfully improve patient outcomes. Nurse-driven interventions, combined with system-wide product changes, and patient and family involvement may be effective strategies that reduce CAUTI. PMID- 22047998 TI - Saturation of the ion-hammering effect for large non-hydrostatic capillarity stresses in colloidal silica nanoparticles. AB - We investigate the role of capillarity stresses on the ion-hammering phenomenon when sub-micrometer colloidal particles are considered. To this end, nearly monodisperse, chemically synthesized silica (SiO2) colloids (100, 300 and 600 nm) were irradiated at room temperature (300 K) with 4 MeV Au ions for fluences up to Phi = 1.8 * 1016 cm-2. It has been taken for granted that the transverse dimension of an ion-deformable amorphous material grows exponentially with the irradiation fluence, L(phi) = L0exp[A0Phi]. Here, we show that for sub-micrometer particles the irradiation-induced deformation saturates for larger fluences, L(phi)->const. The saturation fluence depends on the initial dimension of the colloidal nanoparticles: the smaller the dimension of the colloids, the lower the saturation fluence. Experimental data are successfully accounted for by having recourse to a phenomenological model first developed by Klaumunzer and further elaborated by van Dillen. We also estimate the evolution with fluence of the principal stresses inside the particles, sigma11(phi) = sigma22(phi) and sigma33(phi), and we show that they evolve toward a steady-state value following a sigmoidal-like behavior. Furthermore, when stresses induced by the surface curvature become non-negligible the approximation often made that the deformation strain rate, A0 = dL/L dPhi, remains constant upon irradiation is no longer valid. We show that A0 evolves with the irradiation fluence, e.g. A0->A(Phi), and we relate this behavior to the evolution of the stresses upon irradiation. Finally, this work allows us to define the limits of the ion-hammering effect when the non-hydrostatic capillarity stresses become important. PMID- 22047999 TI - JOSPT perspectives for patients. Low back pain: MRIs should be used sparingly in patients with low back pain. AB - Low back pain is very common, with 80% of people experiencing back pain at least once in their lifetimes. The good news is that a thorough physical examination can often determine the best course of management and whether you require imaging to rule out a serious problem. Often low back pain can be severe enough to make a patient think that an MRI is necessary. While MRI provides excellent pictures of your anatomy, it may not be able to pinpoint the specific source of your pain. A clinical commentary published in the November 2011 issue of JOSPT summarizes research that describes how the increased use of unnecessary imaging may lead to less than favorable results. PMID- 22048000 TI - Novel therapeutic strategies for metastatic prostate cancer in the post-docetaxel setting. AB - Prostate cancer is the most common noncutaneous cancer and the second leading cause of death from cancer in men in most western countries. Advanced prostate cancer is typically sensitive to androgen-deprivation therapy, but invariably progresses to the castration-resistant state. Most current prostate cancer treatments are based on cytotoxicity directed against tumor cells via androgen deprivation therapy or chemotherapy. Chemotherapy with docetaxel represents the standard first-line treatment in patients with castration-resistant prostate cancer (CRPC). Following progression after treatment with docetaxel, cabazitaxel (XRP6258)-prednisone treatment leads to a significantly longer overall survival (OS) time than with mitoxantrone-prednisone. Several other novel agents are currently being evaluated, including sipuleucel-T, abiraterone acetate, and MDV3100, as well as the radionuclide alpharadin. The cell-based immunotherapy sipuleucel-T produces longer OS times in chemotherapy-naive patients, whereas the androgen biosynthesis inhibitor abiraterone acetate results in longer OS times following docetaxel. It is envisioned that these agents will change the standard of care for patients with metastatic CRPC. This review focuses on the clinical development of cabazitaxel and abiraterone acetate. PMID- 22048001 TI - Mitochondrial dynamics and mitophagy in Parkinson's disease: disordered cellular power plant becomes a big deal in a major movement disorder. AB - Parkinson's disease (PD), the most common movement disorder, is characterized by age-dependent degeneration of dopaminergic neurons in the substantia nigra of the mid-brain. Non-motor symptoms of PD, however, precede the motor features caused by dysfunction of the dopaminergic system, suggesting that PD is a systemic disorder. Mitochondrial dysfunction has long been observed in PD patients and animal models, but the mechanistic link between mitochondrial dysfunction and PD pathogenesis is not well understood. Recent studies have revealed that genes associated with autosomal recessive forms of PD such as PINK1 and Parkin are directly involved in regulating mitochondrial morphology and maintenance, abnormality of which is also observed in the more common, sporadic forms of PD, although the autosomal recessive PDs lack Lewy-body pathology that is characteristic of sporadic PD. These latest findings suggest that at least some forms of PD can be characterized as a mitochondrial disorder. Whether mitochondrial dysfunction represents a unifying pathogenic mechanism of all PD cases remains a major unresolved question. PMID- 22048002 TI - Large cell neuroendocrine carcinoma of the lung metastatic to the shoulder joint, causing suprascapular nerve palsy. PMID- 22048003 TI - Emerging opioid abuse in terminal cancer patients taking oral transmucosal fentanyl citrate for breakthrough pain. PMID- 22048004 TI - Preferred and actual involvement of advanced lung cancer patients and their families in end-of-life decision making: a multicenter study in 13 hospitals in Flanders, Belgium. AB - CONTEXT: Death is often preceded by medical decisions that potentially shorten life (end-of-life decisions [ELDs]), for example, the decision to withhold or withdraw treatment. Respect for patient autonomy requires physicians to involve their patients in this decision making. OBJECTIVES: The objective of this study was to examine the involvement of advanced lung cancer patients and their families in ELD making and compare their actual involvement with their previously stated preferences for involvement. METHODS: Patients with Stage IIIb/IV non small cell lung cancer were recruited by physicians in 13 hospitals and regularly interviewed between diagnosis and death. When the patient died, the specialist and general practitioner were asked to fill in a questionnaire. RESULTS: Eighty five patients who died within 18 months of diagnosis were studied. An ELD was made in 52 cases (61%). According to the treating physician, half of the competent patients were not involved in the ELD making, one-quarter shared the decision with the physician, and one-quarter made the decision themselves. In the incompetent patients, family was involved in half of cases. Half of the competent patients were involved less than they had previously preferred, and 7% were more involved. Almost all of the incompetent patients had previously stated that they wanted their family involved in case of incompetence, but half did not achieve this. CONCLUSION: In half of the cases, advanced lung cancer patients-or their families in cases of incompetence-were not involved in ELD making, despite the wishes of most of them. Physicians should openly discuss ELDs and involvement preferences with their advanced lung cancer patients. PMID- 22048005 TI - Determining tamoxifen sensitivity using primary breast cancer tissue in collagen based three-dimensional culture. AB - We developed a three-dimensional assay prepared from primary breast cancer tissue and quantified tumor response to tamoxifen therapy. Freshly harvested breast cancer biopsies obtained at the time of curative surgical resection were fragmented and embedded into collagen I cushions. Changes in proliferation, apoptosis and tumor volume in response to tamoxifen treatment were quantified using image analysis software and optical projection tomography. Individual and collective invasion of epithelial cells into the surrounding collagen I was observed over the course of the experiment using phase contrast light microscopy and histopathological methods. Addition of tamoxifen to preparations derived from ER+ tumors demonstrated a range of response as measured by proliferative and apoptotic markers. In keeping with published data, tamoxifen reduced the percentage of apoptotic cells expressing cleaved caspase-3 (p = 0.02, Poisson regression analysis). Tamoxifen also reduced residual epithelial volume in ER+ tumors (p = 0.001, Mann-Whitney test), but not in ER low/- tumors (p = 0.78). Changes in tumor volume, as measured by optical projection tomography, allowed stratification into responsive and non-responsive tumors. The model mirrors observations of breast cancer response and histopathological changes to tamoxifen in neo-adjuvant trials. This assay provides a method of screening a battery of therapeutics against individual cancers, informing subsequent design of neo adjuvant trials. PMID- 22048006 TI - Precipitation of nanohydroxyapatite on PLLA/PBLG/Collagen nanofibrous structures for the differentiation of adipose derived stem cells to osteogenic lineage. AB - Tissue engineering and nanotechnology have enabled engineering of nanostructured materials to meet the current challenges in bone treatment owing to rising occurrence of bone diseases, accidental damages and defects. Poly(L-lactic acid)/Poly-benzyl-L-glutamate/Collagen (PLLA/PBLG/Col) scaffolds were fabricated by electrospinning and nanohydroxyapatite (n-HA) was deposited by calcium phosphate dipping method for bone tissue engineering (BTE). The abundance and accessibility of adipose derived stem cells (ADSC) may prove to be novel cell therapeutics for bone repair and regeneration. ADSCs were cultured on these scaffolds and were induced to undergo osteogenic differentiation in the presence of PBLG/n-HA for BTE. The cell-biomaterial interactions were analyzed using cell proliferation, SEM and CMFDA dye extraction techniques. Osteogenic differentiation of ADSC was confirmed using alkaline phosphatase activity (ALP), mineralization (ARS) and dual immunofluorescent staining using both ADSC marker protein and Osteocalcin, which is a bone specific protein. The utmost significance of this study is the bioactive PBLG/n-HA biomolecule introduced on the polymeric nanofibers to regulate and improve specific biological functions like adhesion, proliferation and differentiation of ADSC into osteogenic lineage. This was evident from the immunostaining and CMFDA images of ADSCs showing cuboidal morphology, characteristic of osteogenic lineage. The observed results proved that the PLLA/PBLG/Col/n-HA scaffolds promoted greater osteogenic differentiation of ADSC as evident from the enzyme activity and mineralization profiles for bone tissue engineering. PMID- 22048007 TI - Controlling the migration behaviors of vascular smooth muscle cells by methoxy poly(ethylene glycol) brushes of different molecular weight and density. AB - Cell migration is an important biological activity. Regulating the migration of vascular smooth muscle cells (VSMCs) is critical in tissue engineering and therapy of cardiovascular disease. In this work, methoxy poly(ethylene glycol) (mPEG) brushes of different molecular weight (Mw 2 kDa, 5 kDa and 10 kDa) and grafting mass (0-859 ng/cm(2)) were prepared on aldehyde-activated glass slides, and were characterized by X-ray photoelectron spectrometer (XPS) and quartz crystal microbalance with dissipation (QCM-d). Adhesion and migration processes of VSMCs were studied as a function of different mPEG Mw and grafting density. We found that these events were mainly regulated by the grafting mass of mPEG regardless of mPEG Mw and grafting density. The VSMCs migrated on the surfaces randomly without a preferential direction. Their migration rates increased initially and then decreased along with the increase of mPEG grafting mass. The fastest rates (~24 MUm/h) appeared on the mPEG brushes with grafting mass of 300 500 ng/cm(2) depending on the Mw. Cell adhesion strength, arrangement of cytoskeleton, and gene and protein expression levels of adhesion related proteins were studied to unveil the intrinsic mechanism. It was found that the cell substrate interaction controlled the cell mobility, and the highest migration rate was achieved on the surfaces with appropriate adhesion force. PMID- 22048008 TI - Co-delivery of pEGFP-hTRAIL and paclitaxel to brain glioma mediated by an angiopep-conjugated liposome. AB - In this study, we report an angiopep-2 modified cationic liposome (ANG-CLP) for the efficient co-delivery of a therapeutic gene encoding the human tumour necrosis factor-related apoptosis-inducing ligand (pEGFP-hTRAIL) and paclitaxel (PTX) to glioma. The dual targeting co-delivery system (ANG-CLP/PTX/pEGFP-hTRAIL) improved uptake and gene expression not only in U87 MG cells and BCECs, but also in the glioma bed and infiltrating margin of intracranial U87 MG glioma-bearing models. The system selectively induces apoptosis in U87 MG cells while reducing toxicity to BCECs. The results of the pharmacodynamics studies showed that the apoptosis of glioma cells in in vitro BBB models and in U87 MG glioma-bearing mice induced by ANG-CLP/PTX/pEGFP-hTRAIL was more apparent and widespread than that induced by single medication systems and unmodified co-delivery system. More importantly, the median survival time of brain tumour-bearing mice treated with ANG-CLP/PTX/pEGFP-hTRAIL was 69.5 days, significantly longer than that of other groups, even longer than the commercial temozolomide group (47 days). Therefore, the dual targeting co-delivery system is a promising drug delivery strategy against glioma. PMID- 22048009 TI - Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration. AB - Retinal neuroinflammation, mediated by activated microglia, plays a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in age related macular degeneration and retinitis pigmentosa. Targeted drug therapy for attenuation of neuroinflammation in the retina was explored using hydroxyl terminated polyamidoamine (PAMAM) dendrimer-drug conjugate nanodevices. We show that, upon intravitreal administration, PAMAM dendrimers selectively localize within activated outer retinal microglia in two rat models of retinal degeneration, but not in the retina of healthy controls. This pathology-dependent biodistribution was exploited for drug delivery, by covalently conjugating fluocinolone acetonide to the dendrimer. The conjugate released the drug in a sustained manner over 90 days. In vivo efficacy was assessed using the Royal College of Surgeons (RCS) rat retinal degeneration model over a four-week period when peak retinal degeneration occurs. One intravitreal injection of 1 MUg of FA conjugated to 7 MUg of the dendrimer was able to arrest retinal degeneration, preserve photoreceptor outer nuclear cell counts, and attenuate activated microglia, for an entire month. These studies suggest that PAMAM dendrimers (with no targeting ligands) have an intrinsic ability to selectively localize in activated microglia, and can deliver drugs inside these cells for a sustained period for the treatment of retinal neuroinflammation. PMID- 22048010 TI - A cysteine-selective fluorescent probe for the cellular detection of cysteine. AB - A series of coumarin fluorophores (1-3), each bearing a double bond conjugated quinoline unit that can undergo a Michael-type reaction with thiol-containing compounds, is reported. These systems, designed to provide so-called turn-on changes in fluorescence response when exposed to thiols, act as fluorescent chemical sensors for cysteine (Cys), homocysteine (Hcy), and glutathione (GSH). In the case of 1, selectivity for Cys over Hcy and GSH is observed, both in terms of analyte-induced signal enhancement and response time. On the basis of fluorescence spectroscopic analyses, DFT calculations, and pH dependent studies this substrate selectivity is ascribed to steric interactions between the substituents on the quinolone units present in 1 and the targeted thiols, as well as to the comparatively lower pK(a) value of Cys relative to Hcy and GSH. In aqueous solution, probe 1 was found capable of detecting Cys with a detection limit of 10(-7) m. This system was successfully applied to the fluorescence imaging of intracellular Cys in HepG2 cells. PMID- 22048011 TI - Additive effects of elevated C-reactive protein and exposure to Herpes Simplex Virus type 1 on cognitive impairment in individuals with schizophrenia. AB - OBJECTIVES: We investigated the effect of elevated levels of C-reactive protein (CRP) and exposure to Herpes simplex virus type 1 (HSV-1) on the severity of cognitive impairment in individuals with schizophrenia. METHODS: We measured the levels of CRP and of antibodies to HSV-1 in serum samples from 588 individuals with schizophrenia by enzyme immunoassay tests. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and psychiatric symptoms with the Positive and Negative Syndrome Scale (PANSS). The effects of HSV1 and CRP on cognitive functioning were analyzed with linear and logistic regression analyses adjusting for demographic and clinical variables. RESULTS: The individuals with elevated CRP levels and HSV-1 seropositivity had lower RBANS cognitive scores. The strongest effect was found in individuals who had both serological evidence of HSV-1 exposure and elevated levels of CRP. These individuals had odds of 2.35 to have an RBANS Total score<=60 as compared to individuals who were HSV-1 seronegative and who did not have elevated levels of CRP (p=.002). The risks of decreased cognitive functioning associated with HSV-1 exposure and elevated levels of CRP were independent and additive. There was no effect of HSV-1 exposure and CRP levels on the severity of symptoms as measured by the PANSS (all p>.5). CONCLUSIONS: Elevated levels of CRP and exposure to HSV-1 are associated with the severity of cognitive impairment in schizophrenia. These findings indicate that infection and inflammation may play a major role in the cognitive deficits associated with schizophrenia. PMID- 22048012 TI - Prevalence and incidence of diagnosed endometriosis and risk of endometriosis in patients with endometriosis-related symptoms: findings from a statutory health insurance-based cohort in Germany. AB - OBJECTIVE: The objectives were: (a) to determine the administrative prevalence and incidence of endometriosis and (b) to assess the risk of endometriosis associated with endometriosis-related symptoms. STUDY DESIGN: The study is based on inpatient and outpatient data from a statutory health insurance fund in Germany. For prevalence and incidence definition 62,323 women aged 15-54 continuously insured in 2007 were identified. The prevalence and incidence of endometriosis in 2007 were calculated standardized to the age distribution in Germany. In a further prospective cohort study based within the health insurance sample 2095 patients with endometriosis-related symptoms and 8380 age-matched asymptomatic controls were identified. Endometriosis follow-up was from 2004 to 2008. Cox proportional hazard regression was used to examine the risk of endometriosis associated with endometriosis-related symptoms, such as pelvic pain, dysmenorrhoea, dyspareunia, menorrhagia, post-coital bleeding, inter menstrual pain and ovarian cysts. Relative risks (RR) and 95% confidence intervals (CI) were calculated. RESULTS: Standardized prevalence and incidence rates were 8.1 and 3.5 per 1000 women, respectively. The highest prevalence was observed in women aged 35-44 with 12.8 per 1000 women. Median follow-up was 4.5 years. Risk of endometriosis associated with endometriosis-related symptomatology was RR (95% CI)=4.95 (3.67-6.68); 4.5% of all symptomatic women were diagnosed with endometriosis in a median follow-up of 4.5 years. The highest risk was observed in women aged 35-44 [RR (95% CI)=6.29 (4.00-9.90)] with 7.6% of all symptomatic women receiving a diagnosis of endometriosis during the follow-up. CONCLUSION: Prevalence estimates based on population-based administrative data were lower than described in the literature. Risk of endometriosis was increased in women with endometriosis-related symptoms. However, those symptoms were of limited predictive value for endometriosis as only a small proportion of symptomatic patients were diagnosed with endometriosis in the follow-up. PMID- 22048013 TI - Implementation of a Web-based system to improve the transitional care of older adults. AB - We constructed a bidirectional Web-based system to transmit critical patient information in real time between referring nursing homes and a university hospital emergency department (ED) to facilitate the care of patients referred to our ED. Our model was inexpensive, improved measures of information transfer, and increased provider satisfaction. PMID- 22048014 TI - Metastatic endometrial endometrioid carcinoma with clear cell changes to the breast: a case report. AB - Metastasis to breast from extramammary tissue is rare, and endometrial cancer has rarely been reported to metastasize to the breast. An extensive search in the medical literature reveals only 2 cases. They can be easily mistaken for primary breast carcinoma both clinically and radiologically, even with known history of endometrial carcinoma. This report presents a case of a 64-year-old woman who had endometrial carcinoma treated with total hysterectomy and adjuvant radiation and chemotherapy. Three years after the diagnosis, she had evidence of a solitary breast metastasis. To our knowledge, this is the third described case of endometrial cancer metastatic to the breast and the first in which the endometrial carcinoma demonstrates significant clear cell changes. This report is a reminder that although rare, endometrial carcinoma has the potential to metastasize to breast and illustrates how metastatic lesions in the breast can masquerade clinically as a primary carcinoma. Furthermore, essential guidelines necessary to distinguish primary from metastatic lesions in the breast are presented. PMID- 22048015 TI - Electron donor availability for microbial reductive processes following thermal treatment. AB - Thermal treatment is capable of removing significant free-phase chlorinated solvent mass while potentially enhancing bioremediation effectiveness by establishing temperature gradients in the perimeter of the source zone and by increasing electron donor availability. The objectives of this study were to determine the potential for enhanced reductive dechlorination activity at the intermediate temperatures that establish in the perimeter of the heated source zone, and to evaluate the effect of electron donor competition on the performance of the microbial reductive dechlorination process. Microcosms, constructed with tetrachloroethene- (PCE-) and trichloroethene- (TCE-) impacted soils from the Great Lakes, IL, and Ft. Lewis, WA, sites were incubated at temperatures of 24, 35, 50, 70, and 95 degrees C for 4 months. Reductive dechlorination did not occur in microcosms incubated at temperatures above 24 degrees C even though mesophilic PCE-to-cis-1,2-dichloroethene dechlorinators were present in Ft. Lewis soil suggesting electron donor limitations. Five days after cooling the microcosms to 24 degrees C and bioaugmentation with the methanogenic, PCE-to ethene-dechlorinating consortium OW, at least 85% of the initial PCE and TCE were dechlorinated, but dechlorination ceased prior to complete conversion to ethene. Subsequent biostimulation with hydrogen gas mitigated the dechlorination stall, and conversion to ethene resumed. The results of this study demonstrated that temperatures >35 degrees C inhibit reductive dechlorination activity at the Great Lakes and Ft. Lewis sites, and that the majority of reducing equivalents released from the soil matrix during heat treatment are consumed in methanogenesis rather than reductive dechlorination. These observations suggest that bioaugmenting thermal treatment sites with cultures that do not contain methanogens may allow practitioners to realize enhanced dechlorination activity, a potential benefit of coupling thermal treatment with bioremediation. PMID- 22048016 TI - Assessment of total uncertainty in cocaine and benzoylecgonine wastewater load measurements. AB - To check the effectiveness of campaigns preventing drug abuse or indicating local effects of efforts against drug trafficking, it is beneficial to know consumed amounts of substances in a high spatial and temporal resolution. The analysis of drugs of abuse in wastewater (WW) has the potential to provide this information. In this study, the reliability of WW drug consumption estimates is assessed and a novel method presented to calculate the total uncertainty in observed WW cocaine (COC) and benzoylecgonine (BE) loads. Specifically, uncertainties resulting from discharge measurements, chemical analysis and the applied sampling scheme were addressed and three approaches presented. These consist of (i) a generic model based procedure to investigate the influence of the sampling scheme on the uncertainty of observed or expected drug loads, (ii) a comparative analysis of two analytical methods (high performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry), including an extended cross-validation by influent profiling over several days, and (iii) monitoring COC and BE concentrations in WW of the largest Swiss sewage treatment plants. In addition, the COC and BE loads observed in the sewage treatment plant of the city of Berne were used to back-calculate the COC consumption. The estimated mean daily consumed amount was 107 +/- 21 g of pure COC, corresponding to 321 g of street-grade COC. PMID- 22048017 TI - Waterborne transmission of protozoan parasites: review of worldwide outbreaks - an update 2004-2010. AB - The present update gives a comprehensive review of worldwide waterborne parasitic protozoan outbreaks that occurred and were published globally between January 2004 and December 2010. At least one hundred and ninety-nine outbreaks of human diseases due to the waterborne transmission of parasitic protozoa occurred and were reported during the time period from 2004 to 2010. 46.7% of the documented outbreaks occurred on the Australian continent, 30.6% in North America and 16.5% in Europe. Cryptosporidium spp. was the etiological agent in 60.3% (120) of the outbreaks, Giardia lamblia in 35.2% (70) and other protozoa in 4.5% (9). Four outbreaks (2%) were caused by Toxoplasma gondii, three (1.5%) by Cyclospora cayetanensis. In two outbreaks (1%) Acanthamoeba spp. was identified as the causative agent. In one outbreak, G. lamblia (in 17.6% of stool samples) and Cryptosporidium parvum (in 2.7% of stool samples) as well as Entamoeba histolytica (in 9.4% of stool samples) and Blastocystis hominis (in 8.1% of stool samples) were detected. In those countries that are likely affected most a lack of surveillance systems is noticeable. However, countries that established surveillance systems did not establish an international standardization of reporting systems. PMID- 22048018 TI - Modelling the photochemical fate of ibuprofen in surface waters. AB - We show that the main photochemical processes involved in the phototransformation of anionic ibuprofen (IBP) in surface waters are the reaction with (*)OH, the direct photolysis and possibly the reaction with the triplet states of chromophoric dissolved organic matter ((3)CDOM). These conclusions were derived by use of a model of surface water photochemistry, which adopted measured parameters of photochemical reactivity as input data. The relevant parameters are the polychromatic UVB photolysis quantum yield (Phi(IBP) = 0.33 +/- 0.05, MU+/ sigma), the reaction rate constant with (*)OH (k(IBP,*OH)=(1.0 +/- 0.3)?10(10) M( 1) s(-1)), the (1)O(2) rate constant (k(IBP,)( 1O2)= (6.0 +/- 0.6)?10(4) M(-1) s( 1)), while the reaction with CO(3)(-*) can be neglected. We adopted anthraquinone 2-sulphonate (AQ2S) and riboflavin (Ri) as CDOM proxies and the reaction rate constants with the respective triplet states were k(IBP,3AQ2S)=(9.7 +/- 0.2)?10(9) M(-1) s(-1) and k(IBP,3Ri) = 4.5?10(7) M(-1) s(-1). The reaction with (3)CDOM can be an important IBP sink if its rate constant is comparable to that of (3)AQ2S, while it is unimportant if the rate constant is similar to the (3)Ri* one. The photochemical pathways mainly lead to the transformation (oxidation and/or shortening) of the propanoic lateral chain of IBP, which appears to be significantly more reactive than the isobutyl one. Interestingly, none of the detected intermediates was produced by substitution on the aromatic ring. PMID- 22048019 TI - Recycling algae to improve species control and harvest efficiency from a high rate algal pond. AB - This paper investigates the influence of recycling gravity harvested algae on species dominance and harvest efficiency in wastewater treatment High Rate Algal Ponds (HRAP). Two identical pilot-scale HRAPs were operated over one year either with (HRAP(r)) or without (HRAP(c)) harvested algal biomass recycling. Algae were harvested from the HRAP effluent in algal settling cones (ASCs) and harvest efficiency was compared to settlability in Imhoff cones five times a week. A microscopic image analysis technique was developed to determine relative algal dominance based on biovolume and was conducted once a month. Recycling of harvested algal biomass back to the HRAP(r) maintained the dominance of a single readily settleable algal species (Pediastrum sp.) at >90% over one year (compared to the control with only 53%). Increased dominance of Pediastrum sp. greatly improved the efficiency of algal harvest (annual average of >85% harvest for the HRAP(r) compared with ~60% for the control). Imhoff cone experiments demonstrated that algal settleability was influenced by both the dominance of Pediastrum sp. and the species composition of remaining algae. Algal biomass recycling increased the average size of Pediastrum sp. colonies by 13-30% by increasing mean cell residence time. These results indicate that recycling gravity harvested algae could be a simple and effective operational strategy to maintain the dominance of readily settleable algal species, and enhance algal harvest by gravity sedimentation. PMID- 22048020 TI - Reconnaissance of selected PPCP compounds in Costa Rican surface waters. AB - Eighty-six water samples were collected in early 2009 from Costa Rican surface water and coastal locations for the analysis of 34 pharmaceutical and personal care product compounds (PPCPs). Sampling sites included areas receiving treated and untreated wastewaters, and urban and rural runoff. PPCPs were analyzed using a combination of solid phase extraction and liquid chromatography tandem mass spectrometry. The five most frequently detected compounds were doxycycline (77%), sulfadimethoxine (43%), salicylic acid (41%), triclosan (34%) and caffeine (29%). Caffeine had the maximum concentration of 1.1 mg L(-1), possibly due to coffee bean production facilities upstream. Other compounds found in high concentrations include: doxycycline (74 MUg L(-1)), ibuprofen (37 MUg L(-1)), gemfibrozil (17 MUg L(-1)), acetominophen (13 MUg L(-1)) and ketoprofen (10 MUg L(-1)). The wastewater effluent collected from an oxidation pond had similar detection and concentrations of compounds compared to other studies reported in the literature. Waters receiving runoff from a nearby hospital showed higher concentrations than other areas for many PPCPs. Both caffeine and carbamazepine were found in low frequency compared to other studies, likely due to enhanced degradation and low usage, respectively. Overall concentrations of PPCPs in surface waters of Costa Rica are inline with currently reported occurrence data from around the world, with the exception of doxycycline. PMID- 22048021 TI - Linkage disequilibrium under recurrent bottlenecks. AB - To model deviations from selectively neutral genetic variation caused by different forms of selection, it is necessary to first understand patterns of neutral variation. Best understood is neutral genetic variation at a single locus. But, as is well known, additional insights can be gained by investigating multiple loci. The resulting patterns reflect the degree of association (linkage) between loci and provide information about the underlying multilocus gene genealogies. The statistical properties of two-locus gene genealogies have been intensively studied for populations of constant size, as well as for simple demographic histories such as exponential population growth and single bottlenecks. By contrast, the combined effect of recombination and sustained demographic fluctuations is poorly understood. Addressing this issue, we study a two-locus Wright-Fisher model of a population subject to recurrent bottlenecks. We derive coalescent approximations for the covariance of the times to the most recent common ancestor at two loci in samples of two chromosomes. This covariance reflects the degree of association and thus linkage disequilibrium between these loci. We find, first, that an effective population-size approximation describes the numerically observed association between two loci provided that recombination occurs either much faster or much more slowly than the population-size fluctuations. Second, when recombination occurs frequently between but rarely within bottlenecks, we observe that the association of gene histories becomes independent of physical distance over a certain range of distances. Third, we show that in this case, a commonly used measure of linkage disequilibrium, sigma(2)(d) (closely related to r(2)), fails to capture the long-range association between two loci. The reason is that constituent terms, each reflecting the long-range association, cancel. Fourth, we analyze a limiting case in which the long-range association can be described in terms of a Xi coalescent allowing for simultaneous multiple mergers of ancestral lines. PMID- 22048022 TI - Diverse tumor pathology due to distinctive patterns of JAK/STAT pathway activation caused by different Drosophila polyhomeotic alleles. AB - Drosophila polyhomeotic (ph) is one of the important polycomb group genes that is linked to human cancer. In the mosaic eye imaginal discs, while ph(del), a null allele, causes only non-autonomous overgrowth, ph(505), a hypomorphic allele, causes both autonomous and non-autonomous overgrowth. These allele-specific phenotypes stem from the different sensitivities of ph mutant cells to the Upd homologs that they secrete. PMID- 22048023 TI - dSet1 is the main H3K4 di- and tri-methyltransferase throughout Drosophila development. AB - In eukaryotes, the post-translational addition of methyl groups to histone H3 lysine 4 (H3K4) plays key roles in maintenance and establishment of appropriate gene expression patterns and chromatin states. We report here that an essential locus within chromosome 3L centric heterochromatin encodes the previously uncharacterized Drosophila melanogaster ortholog (dSet1, CG40351) of the Set1 H3K4 histone methyltransferase (HMT). Our results suggest that dSet1 acts as a "global" or general H3K4 di- and trimethyl HMT in Drosophila. Levels of H3K4 di- and trimethylation are significantly reduced in dSet1 mutants during late larval and post-larval stages, but not in animals carrying mutations in genes encoding other well-characterized H3K4 HMTs such as trr, trx, and ash1. The latter results suggest that Trr, Trx, and Ash1 may play more specific roles in regulating key cellular targets and pathways and/or act as global H3K4 HMTs earlier in development. In yeast and mammalian cells, the HMT activity of Set1 proteins is mediated through an evolutionarily conserved protein complex known as Complex of Proteins Associated with Set1 (COMPASS). We present biochemical evidence that dSet1 interacts with members of a putative Drosophila COMPASS complex and genetic evidence that these members are functionally required for H3K4 methylation. Taken together, our results suggest that dSet1 is responsible for the bulk of H3K4 di- and trimethylation throughout Drosophila development, thus providing a model system for better understanding the requirements for and functions of these modifications in metazoans. PMID- 22048024 TI - A protosilencer of subtelomeric gene expression in Candida glabrata with unique properties. AB - Adherence to host cells is an important step in the pathogenicity of the opportunistic fungal pathogen Candida glabrata. This adherence is mediated by some members of the large family of cell wall proteins encoded by the EPA (Epithelial Adhesin) genes present in the C. glabrata genome. The majority of the EPA genes are localized close to different telomeres in C. glabrata, resulting in a negative regulation of transcription of these genes through chromatin-based subtelomeric silencing. In vitro, adherence to epithelial cells is mainly mediated by Epa1, the only member of the EPA family that is expressed in vitro. EPA1 forms a cluster with EPA2 and EPA3 at the subtelomeric region of telomere E( R). EPA2 and EPA3 are subject to silencing that propagates from this telomere in a process that depends on the Sir2, -3, -4, and Rif1 proteins, but surprisingly not on the yKu70 and yKu80 proteins. Here we describe that the yKu70/yKu80 independent silencing of telomere E(-R) is due to the presence of a cis-acting protosilencer (Sil2126) located between EPA3 and the telomere. This element can silence a reporter gene when placed 31.9 kb away from this telomere, but not when it is removed from the telomere context, or when it is placed near other telomeres, or inverted with respect to the reporter. Importantly, we show that the cis-acting Sil2126 element is required for the yKu70/80-independent silencing of this telomere, underscoring the importance of cis-elements for repressive chromatin formation and spreading on some telomeres in C. glabrata. PMID- 22048025 TI - RNA meets disease in paradise. AB - Getting off the train in Jena-Paradies, 60 participants joined for the 12 (th) Young Scientist Meeting of the German Society for Cell Biology (DGZ) entitled "RNA & Disease". Excellent speakers from around the world, graduate students, postdocs and young group leaders enjoyed a meeting in a familiar atmosphere to exchange inspiring new data and vibrant scientific discussions about the fascinating history and exciting future of non-coding RNA research including microRNA, piRNA and long non-coding RNA as well as their function in cancer, diabetes and neurodegenerative diseases. PMID- 22048026 TI - Micro RNA -214,-150,-146a and-125b target Huntingtin gene. AB - We observed earlier that expressions of several micro RNAs (miRNAs) are altered in a cell model of Huntington's disease (HD). As genes involved in different neurodegenerative diseases are targeted by miRNAs, we searched databases to find out whether Huntingtin gene (HTT), mutation to which causes HD, is a target of any miRNA. Among many miRNAs that are predicted to target HTT, we showed using various experimental approaches that miR-214, miR-150, miR-146a and miR-125b could target both human HTT and mouse Htt. Luciferase reporter vectors containing 3'-UTRs of mouse and human HTT showed reduction in relative luciferase activities on exogenous expression of cloned miRNAs. Loss of function studies with miRNA inhibitors led to the revival of luciferase activities of cloned 3'-UTR of HTT. Exogenous expression of these miRNAs reduced the expression of endogenous Htt in mouse cells. Expression of miRNAs with mutations at seed sequences neither reduced the reporter luciferase activities nor the endogenous expression of Htt. Taking together, we showed that miR-214, miR-150, miR-146a and miR-125b targeted HTT. Besides, the exogenous expression of wild type miRNAs reduced HTT aggregates formed by the recombinant exon1 of HTT gene that codes for 83Q tagged with 3'-UTR of Htt, as observed by filter retardation assay and confocal microscopy. In summary, regulation of HTT by miRNAs might provide a new mechanism for the modulation of HD. PMID- 22048027 TI - The National Cancer Survivorship Initiative: new and emerging evidence on the ongoing needs of cancer survivors. PMID- 22048028 TI - The health and well-being of cancer survivors in the UK: findings from a population-based survey. AB - BACKGROUND: To compare self-reported health and well-being in a sample of cancer survivors with individuals who have not had cancer and with individuals who have a serious chronic condition other than cancer. PATIENTS AND METHODS: A cross sectional survey drawn from an online panel of 400,000 UK citizens supplemented with other online recruitment and telephone recruitment. The participants were 4892 individuals 30 years of age or above, including 780 individuals with a previous cancer diagnosis, 1372 individuals with one or more of 10 chronic conditions but not cancer and 2740 individuals without a previous cancer diagnosis or chronic condition. Thirteen measures of health and well-being were constructed from answers to 25 survey items covering physical, psychological and social dimensions of health and well-being. RESULTS: Cancer survivors were significantly more likely to report poor health outcomes across all 13 measures than those with no history of cancer or a chronic condition. The adjusted odds ratios for cancer survivors with no chronic conditions compared with healthy participants ranged from 1.37 (95% confidence interval (CI): 1.31-1.96) for emotional well-being to 3.34 (95% CI: 2.74-4.08) for number of health professionals consulted in the last 12 months. The health profile of cancer survivors was similar to those with a history of a serious chronic health condition. CONCLUSIONS: A substantial number of individuals who have had a diagnosis of cancer experience ongoing poor health and well-being following cancer and cancer treatment. The results of this study provide an initial basis for the development of specific help and support for cancer survivors. PMID- 22048029 TI - Recovery and self-management support following primary cancer treatment. AB - BACKGROUND: Around 2 million people are living with or beyond cancer in the UK. However, experiences and needs following primary treatment are relatively neglected. Following treatment, survivors may feel particularly vulnerable and face threats to their identity. We present a conceptual framework to inform areas of self-management support to facilitate recovery of health and well-being following primary cancer treatment. METHODS: To explain the framework, we draw on data from two studies: UK-wide consultation about cancer patients' research priorities and survivors' self-management in the year following primary cancer treatment. RESULTS: Self-confidence may be low following treatment. Recovery includes rebuilding lost confidence. Support to manage the impact of cancer on everyday life was a priority. Self-management support included health professionals, peers, employers, family, friends and online resources. However, support was not always available and confidence to access support could be low. CONCLUSION: Cancer survivors may struggle to self-manage following primary treatment where confidence is low or support is lacking. Low confidence may be a significant barrier to accessing support. Supporting recovery of self-confidence is an important aspect of recovery alongside physical and psychosocial problems in the context of changing health care and cancer follow-up. PMID- 22048030 TI - Long-term health outcomes in a British cohort of breast, colorectal and prostate cancer survivors: a database study. AB - BACKGROUND: The community-based incidence of cancer treatment-related long-term consequences is uncertain. We sought to establish the burden of health outcomes that have been associated with treatment among British long-term cancer survivors. METHODS: We identified 26,213 adults from the General Practice Research Database who have survived 5 years or more following breast, colorectal or prostate cancer. Four age-, sex- and general practice-matched non-cancer controls were selected for each survivor. We considered the incidence of treatment-associated health outcomes using Cox proportional hazards models. RESULTS: Breast cancer survivors had an elevated incidence of heart failure (hazards ratio (HR) 1.95, 95% confidence interval (CI) 1.27-3.01), coronary artery disease (HR 1.27, 95% CI 1.11-1.44), hypothyroidism (HR 1.26, 95% CI 1.02 1.56) and osteoporosis (HR 1.26, 95% CI 1.13-1.40). Among colorectal cancer survivors, there was increased incidence of dementia (HR 1.68, 95% CI 1.20-2.35), diabetes (HR 1.39, 95% CI 1.12-1.72) and osteoporosis (HR 1.41, 95% CI 1.15 1.73). Prostate cancer survivors had the highest risk of osteoporosis (HR 2.49, 95% CI 1.93-3.22). CONCLUSIONS: The study confirms the occurrence of increased incidence of chronic illnesses in long-term cancer survivors attributable to underlying lifestyle and/or cancer treatments. Although the absolute risk of the majority of late effects in the cancer survivors cohort is low, identifying prior risk of osteoporosis by bone mineral density scanning for prostate survivors should be considered. There is an urgent need to improve primary care recording of cancer treatment. PMID- 22048031 TI - A person-time analysis of hospital activity among cancer survivors in England. AB - BACKGROUND: There are around 2 million cancer survivors in the UK. This study describes the inpatient and day case hospital activity among the population of cancer survivors in England. This is one measure of the burden of cancer on the individual and the health service. METHODS: The national cancer registry data set for England (1990-2006) is linked to the NHS Hospital Episode Statistics (HES) database. Cohorts of survivors were defined as those people recorded in the cancer registry data with a diagnosis of breast, colorectal, lung or prostate cancer before 2007. The person-time of prevalence in 2006 for each cohort of survivors was calculated according to the cancer type, sex, age and time since diagnosis. The corresponding HES episodes of care in 2006 were used to calculate the person-time of admitted hospital care for each cohort of survivors. The average proportion of time spent in hospital by survivors in each cohort was calculated as the summed person-time of hospital activity divided by the summed person-time of prevalence. The analysis was conducted separately for cancer related episodes and non-cancer-related episodes. RESULTS: Lung cancer survivors had the highest intensity of cancer-related hospital activity. For all cancers, cancer-related hospital activity was highest in the first year following diagnosis. Breast and prostate cancer survivors had peaks of cancer-related hospital activity in the relatively young and relatively old age groups. The proportion of time spent in hospital for non-cancer-related care was much lower than that for cancer-related care and increased gradually with age but was generally constant regardless of time since diagnosis. CONCLUSION: The person time approach used in this study is more revealing than a simple enumeration of cancer survivors and hospital admissions. Hospital activity among cancer survivors is highest soon after diagnosis. The effect of age on the amount of hospital activity is different for each type of cancer. PMID- 22048032 TI - A qualitative study of unmet needs and interactions with primary care among cancer survivors. AB - INTRODUCTION: Despite increasing numbers, there is little research investigating the long-term needs of cancer survivors. The aim of this study is to explore the experiences of individuals who have survived at least 5 years following a cancer diagnosis, and to describe perceived unmet needs and interactions with primary care. METHODS: Forty long-term survivors of breast, colorectal and prostate cancer were purposively selected for an in-depth qualitative study. We aimed for a maximum variation sample according to cancer site, gender, time since diagnosis, cancer needs, anxiety and depression. Interviews were audio recorded and transcribed verbatim. Transcripts were coded thematically using a grounded theory approach. RESULTS: Analysis of the interview data is presented in four subthemes: the role they perceived for the general practitioner (GP), unmet needs, reasons for not using primary care for needs they perceived as cancer related, and ongoing care for cancer-related issues. The majority of cancer survivors did not see a role for their GP in their long-term care related to their cancer diagnosis as most considered that they did not need active follow up, but some expressed a need for psychological services and information on possible long-term effects. Cancer survivors cited three main reasons for not using GP services in relation to their cancer diagnosis: GPs were seen as non experts in cancer; they were perceived as too busy; and a lack of continuity within primary care made it difficult to talk about long-term issues. There was a wide variation in schedules and notification of PSA tests among the prostate cancer survivors. DISCUSSION: The results from this project suggest that some cancer survivors have specific emotional and physical needs that could benefit from input from their primary care team, but not all cancer survivors look to their GP for their long-term cancer-related care. Better information care planning is required from specialists in order to identify those who would benefit most. PMID- 22048033 TI - New pathways of care for cancer survivors: adding the numbers. AB - BACKGROUND: Two million people in the UK had a cancer diagnosis at the end of 2008. Understanding the number of people diagnosed with cancer with and without health needs is valuable information that can be used to inform service planning, treatment provision and support for people at the right time in the right place as demand grows over time. METHODS: Using available data and clinically led assumptions about patient need and outcomes, we make indicative estimates. We quantify, for three common cancers, the number of people in each of the five main identified phases of the cancer care pathway. RESULTS: Estimates are provided for each phase of the pathway for breast, colorectal and lung cancers. We estimate that there are nearly 575,000 women a year with breast cancer in the care pathway at some point in the year, 8% are in the rehabilitation phase and 4% in the progressive illness phase. This compares to nearly 270,000 with colorectal and around 95,000 with lung cancer. CONCLUSION: Using readily available data, we estimate the numbers of patients with different health needs. These numbers could inform the targeting of resources for service providers. PMID- 22048034 TI - The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature. AB - BACKGROUND: Evidence for the role of diet and physical activity in cancer incidence is well documented, but owing to increased cancer survivorship, an understanding of these lifestyle factors after a cancer diagnosis is of crucial importance. The purpose of this review was to update the literature in a review undertaken for the National Cancer Survivorship Initiative and to include observational studies that were not included in the WCRF survivorship systematic review. METHODS: Evidence was initially gathered from pre-defined searches of the Cochrane Library Database and PubMed from March 2006 to February 2010. After a comprehensive review regarding lifestyle and cancer, for the purpose of this article, any studies not related to diet and physical activity, prognostic outcomes, and breast, colorectal or prostate cancers were excluded. Another search of 2011 literature was conducted to update the evidence. RESULTS: A total of 43 records were included in this review. Evidence from observational studies suggests that a low-fat, high-fibre diet might be protective against cancer recurrence and progression. However, there is a paucity of RCTs substantiating this. There is more support for physical activity, with a dose response for better outcomes. When synthesized with findings from the World Cancer Research Fund review of RCTs investigating the effect of diet and physical activity interventions on cancer survival, evidence suggests that the mechanism of benefit from diet and physical activity pertains to body weight, with excess body weight being a risk factor, which is modifiable through lifestyle. IMPLICATIONS: Cancer survivors would like to have a more active role in their health care and to know how to look after themselves after diagnosis, including what diet and lifestyle changes they should make. The challenge is in integrating lifestyle support into standardised models of aftercare. PMID- 22048035 TI - Integrating cancer survivors' experiences into UK cancer registries: design and development of the ePOCS system (electronic Patient-reported Outcomes from Cancer Survivors). AB - BACKGROUND: Understanding the psychosocial challenges of cancer survivorship, and identifying which patients experience ongoing difficulties, is a key priority. The ePOCS (electronic patient-reported outcomes from cancer survivors) project aims to develop and evaluate a cost-efficient, UK-scalable electronic system for collecting patient-reported outcome measures (PROMs), at regular post-diagnostic timepoints, and linking these with clinical data in cancer registries. METHODS: A multidisciplinary team developed the system using agile methods. Design entailed process mapping the system's constituent parts, data flows and involved human activities, and undertaking usability testing. Informatics specialists built new technical components, including a web-based questionnaire tool and tracking database, and established component-connecting data flows. Development challenges were overcome, including patient usability and data linkage and security. RESULTS: We have developed a system in which PROMs are completed online, using a secure questionnaire administration tool, accessed via a public-facing website, and the responses are linked and stored with clinical registry data. Patient monitoring and communications are semiautomated via a tracker database, and patient correspondence is primarily Email-based. The system is currently honed for clinician-led hospital-based patient recruitment. CONCLUSIONS: A feasibility test study is underway. Although there are possible challenges to sustaining and scaling up ePOCS, the system has potential to support UK epidemiological PROMs collection and clinical data linkage. PMID- 22048036 TI - Knowledge, ignorance and priorities for research in key areas of cancer survivorship: findings from a scoping review. AB - BACKGROUND: Patients who have completed initial cancer treatment (cancer survivors) have been relatively neglected. We need data to help us better understand the needs of this group and to underpin evidence-based service development. METHODS: Scoping reviews of research published in the last two decades focussing on the problems faced by cancer survivors, and the effectiveness of interventions for these problems were undertaken. The aim was to identify what we know, what we do not know and opportunities where research could provide new information. We searched for, retrieved and rapidly appraised systematic reviews sourced from the most common electronic databases supplemented by more recently published individual studies. RESULTS: The research evidence is surprisingly limited. We have some knowledge of the prevalence and nature of depression, pain and fatigue in cancer survivors. We know much less about cognitive and physical impairment, employment, financial well-being and relationships. Even where we have evidence, it is mostly of only moderate quality, is most often only for breast cancer and focuses almost exclusively on the early phase of survivorship. We have good evidence for the effectiveness of drug treatments for pain and moderate evidence for fatigue and depression, but not for other symptoms. Interventions based on rehabilitative and self-management approaches remain in the early stages of evaluation. INTERPRETATION: There has been a substantial amount of research describing many of the problems experienced by the cancer survivors. This is strongest in the area of symptoms in the period soon after treatment. However, the quality of the evidence is often poor, and some topics have been little examined. We urgently need data on the natural evolution and scale of the problems of cancer survivors obtained from well designed, large-scale cohort studies and the robust testing of interventions in clinical trials. Given the current financially constrained research funding environment, we suggest areas in which strategic investment might give findings that have the potential to make a major impact on patient well-being in a 5-year time scale. PMID- 22048037 TI - Looking for natural variation in chiasma frequency in Arabidopsis thaliana. AB - Information concerning natural variation either in chiasma frequency or in the genetic basis of any such variation is a valuable tool to characterize phenotypic traits and their genetic control. Here meiotic recombination frequencies are analysed in nine geographically and ecologically diverse accessions of Arabidopsis thaliana, and a comparative study was carried out incorporating previous data from another eight accessions. Chiasma frequencies, estimated by counting rod and ring bivalents at metaphase I, varied up to 22% among accessions. However, no differences were found among plants of the same accession. There was a relationship, which does not necessarily imply direct proportionality, between the size of the chromosomes and their mean chiasma frequency. Chiasma frequency and distribution between arms and among chromosomes were not consistent over accessions. These findings indicate the existence of genetic factors controlling meiotic recombination both throughout the whole genome and at the whole chromosome level. The reliability of chiasma scoring as an indicator of reciprocal recombination events is also discussed. PMID- 22048038 TI - The expression pattern of the Picea glauca Defensin 1 promoter is maintained in Arabidopsis thaliana, indicating the conservation of signalling pathways between angiosperms and gymnosperms. AB - A 1149 bp genomic fragment corresponding to the 5' non-coding region of the PgD1 (Picea glauca Defensin 1) gene was cloned, characterized, and compared with all Arabidopsis thaliana defensin promoters. The cloned fragment was found to contain several motifs specific to defence or hormonal response, including a motif involved in the methyl jasmonate reponse, a fungal elicitor responsive element, and TC-rich repeat cis-acting element involved in defence and stress responsiveness. A functional analysis of the PgD1 promoter was performed using the uidA (GUS) reporter system in stably transformed Arabidopsis and white spruce plants. The PgD1 promoter was responsive to jasmonic acid (JA), to infection by fungus and to wounding. In transgenic spruce embryos, GUS staining was clearly restricted to the shoot apical meristem. In Arabidopsis, faint GUS coloration was observed in leaves and flowers and a strong blue colour was observed in guard cells and trichomes. Transgenic Arabidopsis plants expressing the PgD1::GUS construct were also infiltrated with the hemibiotrophic pathogen Pseudomonas syringae pv. tomato DC3000. It caused a suppression of defensin expression probably resulting from the antagonistic relationship between the pathogen stimulated salicylic acid pathway and the jasmonic acid pathway. It is therefore concluded that the PgD1 promoter fragment cloned appears to contain most if not all the elements for proper PgD1 expression and that these elements are also recognized in Arabidopsis despite the phylogenetic and evolutionary differences that separates them. PMID- 22048039 TI - Characterization of the plastid-specific germination and seedling establishment transcriptional programme. AB - Upon imbibition, dry seeds rapidly gain metabolic activity and the switching on of a germination-specific transcriptional programme in the nucleus goes ahead, with the induction of many nucleus-encoded transcripts coding for plastid localized proteins. Dedifferentiated plastids present in dry seeds differentiate into chloroplasts in cotyledons and into amyloplasts in the root and in the hypocotyl, raising the question of whether the beginning of a new plant's life cycle is also characterized by specific changes in the plastid transcriptional programme. Here the plastid transcriptome is characterized during imbibition/stratification, germination, and early seedling outgrowth. It is shown that each of these three developmental steps is characterized by specific changes in the transcriptome profile, due to differential activities of the three plastid RNA polymerases and showing the integration of plastids into a germination specific transcriptional programme. All three RNA polymerases are active during imbibition; that is, at 4 degrees C in darkness. However, activity of plastid encoded RNA polymerase (PEP) is restricted to the rrn operon. After cold release, PEP changes specificity by also transcribing photosynthesis-related genes. The period of germination and radicle outgrowth is further characterized by remarkable antisense RNA production that diminishes during greening when photosynthesis-related mRNAs accumulate to their highest but to very different steady-state levels. During stratification and germination mRNA accumulation is not paralleled by protein accumulation, indicating that plastid transcription is more important for efficient germination than translation. PMID- 22048040 TI - Developmental and stress regulation of gene expression for a 9-cis epoxycarotenoid dioxygenase, CstNCED, isolated from Crocus sativus stigmas. AB - Oxidative cleavage of cis-epoxycarotenoids by 9-cis-epoxycarotenoid dioxygenase (NCED) is the critical step in the regulation of abscisic acid (ABA) synthesis in higher plants. ABA has been associated with dormancy and flower senescence, while also regulating plant adaptive responses to various environmental stresses. An NCED gene, CstNCED, was cloned from Crocus sativus stigmas. The deduced amino acid sequence of the CstNCED protein shared high identity with other monocot NCEDs, and was closely related to the liliopsida enzymes. At the N-terminus of CstNCED a chloroplast transit peptide sequence is located. However, its expression in chloroplast-free tissues suggested localization in other plastid types. The relationship between expression of CstNCED and the endogenous ABA level was investigated in the stigma and corms, where it was developmentally regulated. The senescence of the unpollinated stigma is preceded by an increase in ABA levels and CstNCED expression. In corms, a correlation was observed between CstNCED expression and dormancy. Furthermore, CstNCED expression was correlated with the presence of zeaxanthin in the dormant corms. When detached C. sativus leaves and stigmas were water and salt stressed, increases in CstNCED mRNA were observed. The results provided evidence of the involvement of CstNCED in the regulation of ABA-associated processes such as flower senescence and corm dormancy in monocotyledonous saffron. PMID- 22048041 TI - Perinatal risk factors for bronchopulmonary dysplasia in extremely low gestational age infants: a pregnancy disorder-based approach. AB - OBJECTIVE: To analyze risk factors for bronchopulmonary dysplasia (BPD) or death according to the condition leading to extremely preterm birth, preterm labor, or vascular disorders. STUDY DESIGN: Retrospective study of all premature births before 28 weeks of gestation in a single Level III institution. Mother/infants were attributed to the "preterm labor" or "vascular disorder" group according to the condition leading to delivery. Characteristics and outcomes were compared between groups. Independent risk factors for BPD or the composite outcome "BPD or death" were identified within each group. RESULTS: Three hundred ninety-six infants from 349 pregnancies were characterized for perinatal characteristics. BPD was significantly more frequent in the vascular disease group than in the preterm labor group (29% vs 11%, P < .01). Independent risk factors of BPD were a low gestational age in the preterm labor group and severe growth restriction in the vascular disease group. CONCLUSION: Classification of preterm birth according to the condition leading to delivery might help to reduce confounding of risk factors for BPD. Intrauterine vascular disorders are significantly associated with BPD. PMID- 22048042 TI - Sensing and responding to compliance changes during manual ventilation using a lung model: can we teach healthcare providers to improve? AB - OBJECTIVE: To test the hypothesis that an educational intervention would improve the resuscitator's ability to provide on-target volume ventilation during pulmonary compliance changes. STUDY DESIGN: Neonatal professionals (n = 27) ventilated an electromechanical lung model simulating a 3-kg baby while targeting a tidal volume of 4-6 mL/kg. In this preintervention and postintervention study, a one-on-one educational intervention aimed to improve the primary outcome of on target tidal volume delivery during high and low compliance. Seventeen subjects were retested 8 months later. RESULTS: When only pressure was displayed, and using a self-inflating bag, participants improved from a mean of 6% of breaths on target to 21% immediately after education (P < .01). Using a flow-inflating bag, participants improved from 1% to 7% of breaths on-target (P < .01). Eight-month retention testing demonstrated no difference compared with baseline. With volume displayed, the mean baseline success rate was 84% with the self-inflating bag and 68% with the flow-inflating bag. There was no significant change after education or at 8-month follow-up. CONCLUSION: When pressure is displayed, resuscitators can improve their ability to respond to changes in compliance after an educational intervention. When volume is displayed, performance is markedly better at baseline, but not improved after the intervention. Our findings reconfirm that resuscitation bags should have volume displays. PMID- 22048043 TI - Neurologic outcomes in very preterm infants undergoing surgery. AB - OBJECTIVE: To investigate the relationship between surgery in very preterm infants and brain structure at term equivalent and 2-year neurodevelopmental outcome. STUDY DESIGN: A total of 227 infants born at <30 weeks gestation or at a birth weight of <1250 g were prospectively enrolled into a longitudinal observational cohort for magnetic resonance imaging and developmental follow-up. The infants were categorized retrospectively into either a nonsurgical group (n=178) or a surgical group (n=30). Nineteen infants were excluded because of incomplete or unsuitable data. The surgical and nonsurgical groups were compared in terms of clinical demographic data, white matter injury, and brain volume at term. Neurodevelopmental outcome was assessed at age 2 years. RESULTS: Compared with the nonsurgical group, the infants in the surgical group were smaller and more growth-restricted at birth, received more respiratory support and oxygen therapy, and had longer hospital stays. They also had smaller brain volumes, particularly smaller deep nuclear gray matter volumes. Infants who underwent bowel surgery had greater white matter injury. Mental Developmental Index scores were lower in the surgical group, whereas Psychomotor Developmental Index scores did not differ between the groups. The Mental Developmental Index difference became nonsignificant after adjustment for confounding variables. CONCLUSION: Preterm infants exposed to surgery and anesthesia had greater white matter injury and smaller total brain volumes, particularly smaller deep nuclear gray matter volumes. Surgical exposure in the preterm infant should alert the clinician to an increased risk for adverse cognitive outcome. PMID- 22048044 TI - Facial dysmorphism and skin manifestations in a patient with inherited systemic hyalinosis. PMID- 22048045 TI - Changes in brown adipose tissue in boys and girls during childhood and puberty. AB - OBJECTIVE: To characterize the changes in brown adipose tissue (BAT) occurring during puberty in boys and girls. STUDY DESIGN: We examined the prevalence and the volume of BAT at different stages of sexual development in 73 pediatric patients who underwent positron emission tomography (PET)/computed tomography (CT) studies. RESULTS: Of the 73 patients studied, 43 (59%) had BAT depicted on PET/CT. The presence of BAT was detected significantly less frequently on PET/CT in prepubertal subjects (Tanner stage 1) than in pubertal subjects (Tanner stages 2-5) (15% vs 75%). BAT volume also increased during puberty, with a significantly greater magnitude of the increase in the final 2 stages of puberty (Tanner stages 4 and 5) than in earlier stages (Tanner stages 1-3) (boys: 499 +/- 246 vs 50 +/- 36, P < .0001; girls: 286 +/- 139 vs 36 +/- 29, P = .024). Changes in BAT volume were also significantly greater in boys than in girls (P = .004) and were closely related to muscle volume (r = 0.52, P < .01 for boys; r = 0.64, P < .01 for girls). CONCLUSION: The presence and volume of BAT increase rapidly during puberty. Metabolic and hormonal events related to the achievement of sexual maturity are likely responsible for this increase. PMID- 22048046 TI - Relationship between test scores using the second and third editions of the Bayley Scales in extremely preterm children. AB - OBJECTIVE: To define the relationship between current Bayley Scales of Infant and Toddler Development, Third edition (Bayley-III) scores and the Bayley Scales of Infant Development, second edition Mental Development Index (MDI) to aid the comparison of population outcomes. STUDY DESIGN: MDI and Bayley-III cognitive/language scales were administered concurrently in 185 extremely preterm children (<=26 weeks) at 29-41 months of age. Cognitive and language scores were combined (combined Bayley-III score [CB-III scores]) for comparison with MDI scores. RESULTS: Bayley-III cognitive and language scores were 10 and 3 points higher than MDI scores, respectively; CB-III scores were 7 points higher. The relationship between CB-III and MDI scores was not a simple offset: CB-III values were increasingly higher than MDI at lower scores. Bayley-III scores underidentified MDI scores <70 (sensitivity 58%; specificity 100%). An algorithm for converting Bayley-III scores into MDI scores improved predictive value (sensitivity 95%; specificity 97%). Bayley-III scores <80 were similarly predictive (sensitivity 89%; specificity 99%). CONCLUSIONS: We recommend caution in the interpretation of Bayley-III scores in population studies as the correlation with the previous edition appears worse at lower test score values and the predictive value for IQ is as yet unclear. PMID- 22048047 TI - Correlation of N-terminal fragment of B-type natriuretic peptide levels with clinical, laboratory, and echocardiographic abnormalities in children with sickle cell disease. AB - OBJECTIVE: To determine whether the N-terminal fragment of B-type natriuretic peptide (NTproBNP) was a biomarker of clinical, laboratory, and echocardiographic abnormalities in children with homozygous sickle cell disease. STUDY DESIGN: We conducted a single-center retrospective study that consisted of analysis of data from November 2007 to December 2010. We correlated serum NTproBNP with clinical and laboratory findings, echocardiographic data, and New York Heart Association (NYHA) functional class. RESULTS: NTproBNP levels from 42 children (median age, 9 years; 52% female) had significant correlations with hemoglobin (r = -0.63, P < .05), and echocardiographic measurements including tricuspid regurgitant velocity (r = 0.46, P < .05), lateral E' (r = -0.52, P < .05), and lateral E/E' ratio (r = 0.60, P < .05), suggesting diastolic dysfunction. In addition, NTproBNP levels increased from NYHA functional class I to class III and had a significant linear correlation with the NYHA functional class (r = 0.69, P < .05). CONCLUSIONS: NTproBNP correlated with low hemoglobin and tissue Doppler data as indicators of diastolic dysfunction. Elevated NTproBNP may be a prognostic biomarker for the presence of diastolic dysfunction related to anemia in children with sickle cell disease. PMID- 22048048 TI - Underlying genetic diagnosis of Pierre Robin sequence: retrospective chart review at two children's hospitals and a systematic literature review. AB - OBJECTIVES: To determine the underlying genetic diagnosis of Pierre Robin sequence (PRS) in 2 cohorts of individuals, assess the accuracy of genetic evaluation in young infants with PRS, and contrast the interventions provided to children with isolated and syndromic PRS. STUDY DESIGN: The study involved retrospective chart reviews at 2 children's hospitals and a systematic literature review. RESULTS: Approximately 40% of the patients had isolated PRS, and 60% of the patients had additional syndromic features. The patients with PRS with syndromic features required more aggressive medical management. Stickler syndrome was the most common syndromic diagnosis in PRS. The difficulty of making an accurate genetic diagnosis during the neonatal period was demonstrated. CONCLUSION: All infants with PRS should be evaluated to check for the presence of syndromic features, and a longitudinal follow-up is warranted to monitor for the development of any syndromic features. PMID- 22048049 TI - Women, breastfeeding, and cholesterol levels. PMID- 22048050 TI - Proton magnetic resonance spectroscopic images in preterm infants with bilirubin encephalopathy. AB - Two preterm infants with athetoid cerebral palsy due to bilirubin encephalopathy were examined by magnetic resonance spectroscopic imaging at age 3 years. An increased glutamate/glutamine complex/creatine ratio was found in the basal ganglia. Chemical metabolic abnormalities of the basal ganglia were clearly demonstrated by color-coded metabolite images. PMID- 22048051 TI - Correlates and trends in training satisfaction on completion of internal medicine pediatrics residency: a 5-year study. AB - OBJECTIVE: To examine trends in training satisfaction in graduates of combined internal medicine-pediatrics (Med-Peds) training programs and whether curricular elements designed to enhance the integration of the two disciplines have been successful. STUDY DESIGN: We conducted a cross-sectional survey of all graduating Med-Peds residents (years 2003-2007). Responses across survey years were analyzed to identify trends. Data for all survey years was analyzed for correlations among curricular elements, perceived adequacy of training, and preparation for future activities. RESULTS: Overall, residents rated training time as just right for all areas except neonatal intensive care unit training, outpatient procedures, career planning, and office management. There was a significant upward trend in availability of board examination reviews, Med-Peds noon conferences, and mentoring. Residents' ratings of their preparation for most activities increased across the years. More residents reported being satisfied with preparation for internal medicine than pediatric primary care practice (86% versus 83%). Career planning seminars, mentoring, and board reviews correlated with the greatest increase in satisfaction. CONCLUSIONS: Med-Peds graduates report a high and increasing level of satisfaction with their preparation in multiple educational domains. Curricular elements designed to enhance integration of the two disciplines have a broad positive impact. Perceived pediatric practice preparation lags behind that of internal medicine. PMID- 22048053 TI - Accuracy and precision of the signs and symptoms of streptococcal pharyngitis in children: a systematic review. AB - OBJECTIVE: To conduct a systematic review to determine whether clinical findings can be used to rule in or to rule out streptococcal pharyngitis in children. STUDY DESIGN: Two authors independently searched MEDLINE and EMBASE. We included articles if they contained data on the accuracy of symptoms or signs of streptococcal pharyngitis, individually or combined into prediction rules, in children 3-18 years of age. RESULTS: Thirty-eight articles with data on individual symptoms and signs and 15 articles with data on prediction rules met all inclusion criteria. In children with sore throat, the presence of a scarlatiniform rash (likelihood ratio [LR], 3.91; 95% CI, 2.00-7.62), palatal petechiae (LR, 2.69; CI, 1.92-3.77), pharyngeal exudates (LR, 1.85; CI, 1.58 2.16), vomiting (LR, 1.79; CI, 1.58-2.16), and tender cervical nodes (LR, 1.72; CI, 1.54-1.93) were moderately useful in identifying those with streptococcal pharyngitis. Nevertheless, no individual symptoms or signs were effective in ruling in or ruling out streptococcal pharyngitis. CONCLUSIONS: Symptoms and signs, either individually or combined into prediction rules, cannot be used to definitively diagnose or rule out streptococcal pharyngitis. PMID- 22048052 TI - Reliability of resting blood pressure measurement and classification using an oscillometric device in children with chronic kidney disease. AB - OBJECTIVE: To compare the reliability of blood pressure (BP) readings obtained with an oscillometric device with those obtained by auscultation and assess for differences in BP status classification based on the 2 techniques. STUDY DESIGN: Resting BP was measured by auscultation and with an oscillometric device at the same encounter in 235 subjects enrolled in the Chronic Kidney Disease in Children study. Resting auscultatory BP values were averaged and compared with averaged oscillometric readings. BP agreement by the 2 methods was assessed using Bland Altman plots, and BP status classification agreement was assessed by calculation of kappa statistics. RESULTS: Oscillometric BP readings were higher than auscultatory readings, with a median paired difference of 9 mm Hg for systolic BP (SBP) and 6 mm Hg for diastolic BP (DBP). Correlation for mean SBP was 0.624 and for mean DBP was 0.491. The bias for oscillometric BP measurement was 8.7 mm Hg for SBP (P < .01) and 5.7 mm Hg for DBP (P < .01). BP status classification agreement was 61% for SBP and 63% for DBP, with Kappa values of .31 for SBP and .20 for DBP. CONCLUSIONS: Compared with auscultation, the oscillometric device significantly overestimated both SBP and DBP, leading to frequent misclassification of BP status. PMID- 22048054 TI - Recombinant parathyroid hormone therapy for severe neonatal hypoparathyroidism. PMID- 22048055 TI - Interinstitutional variability in home care interventions after neonatal intensive care unit discharge. PMID- 22048056 TI - Development and pretesting of a decision-aid to use when counseling parents facing imminent extreme premature delivery. AB - OBJECTIVE: To develop and pretest a decision-aid to help parents facing extreme premature delivery during antenatal counseling regarding delivery room resuscitation. STUDY DESIGN: Semistructured interviews with 31 clinicians and with 30 parents of children born <26 weeks' gestation were conducted following standard methods of qualitative research. These characterized perceptions of prenatal counseling to identify information that parents value when making decisions regarding delivery room resuscitation. These parental needs were formatted into a decision-aid. We assessed the primary outcome of how effectively the decision-aid improved knowledge during a simulated counseling session. Two groups of women were studied: parents with a history of prematurity ("experienced") and healthy women without prior knowledge of prematurity ("naive"). RESULTS: Interviewees thought that visual formats to present survival and short- and long-term outcome information facilitated their own preparation, recall, and understanding. Accordingly, we designed a decision-aid as a set of cards with pictures and pictographs to show survival rates and complications. There was significant improvement in knowledge in 13 "experienced" parents (P = .04) and 11 "naive" women (P < .0001). Participants found the cards useful and easy to understand. CONCLUSIONS: A decision-aid for parents facing extreme premature delivery may improve their understanding of complicated information during antenatal counseling. PMID- 22048057 TI - A summary of the new phenomenon of normocalcemic hyperparathyroidism and appropriate management. AB - PURPOSE OF REVIEW: The phenomenon of normocalcemic hyperparathyroidism (NCHPT) remains largely unknown and not well understood. Recently, with more investigators reporting on the subject, NCHPT has been proposed to be a precursor of the classic hypercalcemic primary hyperparathyroidism (HPT). RECENT FINDINGS: This manuscript will discuss the most recent findings regarding the diagnosis, natural history, treatment and follow-up of NCHPT. Approximately 1-4% of patients undergoing parathyroidectomy for HPT are normocalcemic before surgery. To date, observation appears to be a well tolerated approach, as long as these patients remain normocalcemic. When patients with NCHPT are followed for an average of 4 years, 22% will progress to hypercalcemia. In some instances, NCHPT may be treated with parathyroidectomy, but the indications and long-term outcome for this approach are unknown. SUMMARY: This condition is now being diagnosed more frequently. Patients with vitamin D deficiency, mild renal dysfunction, and urinary calcium leak are often mislabeled as having NCHPT and these conditions should always be excluded and medically treated. There is some evidence that parathyroidectomy may be beneficial when NCHPT patients are properly selected. The authors suggest caution when approaching these patients surgically because multiglandular disease and operative failure may be more common in these rare patients. PMID- 22048058 TI - Role of tracheal resection in thyroid cancer. AB - PURPOSE OF REVIEW: To provide a critical review of recent literature on the role of tracheal resection in thyroid cancer. RECENT FINDINGS: The current body of literature is centered on the controversy regarding how radical the extent of tracheal resection needs to be to achieve long-term control of thyroid carcinoma with tracheal invasion. Proponents of shave excision are guided by the reported survival outcomes comparable to segmental resections in a selected group of patients. Others believe that all patients should have a segmental sleeve resection to ensure clearance of transmural disease. Recent advances in microsurgical reconstruction may allow selected patients to undergo tracheal resection when a large tracheal defect is anticipated. SUMMARY: Tracheal invasion by well differentiated carcinoma is a marker of a more aggressive tumor behavior, defining a subpopulation of patients at a greater risk of recurrence and death. The goal of surgical intervention in this scenario is complete resection with no gross residual disease. A well designed prospective multi-institutional trial, taking into account depth of invasion, risk group stratification, histology, presence of distant metastasis, radioactive iodine trapping ability, adjuvant treatment, and long-term survival data, is needed to compare the outcomes following more conservative shave excision and segmental tracheal resection. PMID- 22048059 TI - Education determines a nation's health, but what determines educational outcomes? A cross-national comparative analysis. AB - This study is premised on the notion that public health policy should address not only health itself, but also primary determinants of health. We examined the effect of national policies on educational outcomes, in particular, on adolescent reading literacy (ARL). We compared the effect of traditional policy indicators- national income and educational spending--with income inequality, a measure of redistributive policies. We used Organization for Economic Cooperation and Development (OECD) data that provide a rare opportunity to test policy effects after accounting for competing individual-, school-, and country-level explanations. Our sample consisted of 119,814 students, 5126 schools, and 24 countries. Multilevel/Hierarchical regression findings were striking: GDP had a significant, but negligible effect on ARL scores (beta=0.002, SE=0.0008), while educational spending had no significant effect. By contrast, income inequality exhibited a larger inverse association (beta=-1.15, SE=0.57). Among the wealthy nations in OECD, additional economic prosperity and educational spending is trumped by distribution of income for its effect on ARL. Our study yielded a striking result about education, a major determinant of health. Not only is income inequality a significant determinant of ARL scores, but direct spending on education and overall national economic prosperity are not. PMID- 22048060 TI - Lessons from SARS and H1N1/A: employing a WHO-WTO forum to promote optimal economic-public health pandemic response. AB - No formal system exists to review trade restrictions imposed during international public health emergencies rapidly. Failure to put one in place creates disincentives for surveillance and reporting, thereby undermining protection efforts. The 2003 SARS outbreak exposed weaknesses in global governance that caused uncoordinated public health and economic responses. New International Health Regulations (IHR), applied first during the 2009 H1N1 influenza outbreak, demonstrated improvement. Yet they failed to allow for management of public health emergencies in a way that balanced threats to health and those to economies and trade. Establishment of a joint WHO-WTO committee to adjudicate these conflicts might better achieve that balance. PMID- 22048061 TI - Virtual reality in neuroscience research and therapy. AB - Virtual reality (VR) environments are increasingly being used by neuroscientists to simulate natural events and social interactions. VR creates interactive, multimodal sensory stimuli that offer unique advantages over other approaches to neuroscientific research and applications. VR's compatibility with imaging technologies such as functional MRI allows researchers to present multimodal stimuli with a high degree of ecological validity and control while recording changes in brain activity. Therapists, too, stand to gain from progress in VR technology, which provides a high degree of control over the therapeutic experience. Here we review the latest advances in VR technology and its applications in neuroscience research. PMID- 22048064 TI - Neurodegenerative disease: CRF is the culprit. PMID- 22048065 TI - Scalable nano-patterning of graphenes using laser shock. AB - Nano-patterning of graphene film by a novel approach making use of laser ablation generated pressure is presented in this paper. Arrays of nanoscale holes were fabricated by applying laser shock pressure on graphene film suspended on well trenches in silicon substrate. Round holes with diameters ranging from 50 to 200 nm on graphene film were successfully punched. The critical pressure was found to be dependent on the diameter of holes. The smaller the diameters, the higher the critical pressure, which was also captured by the molecular dynamic (MD) simulations. The laser shock based approach presented in this paper provides an effective way to pattern graphene film with nanoscale features in an easy, fast, and scalable manner. PMID- 22048062 TI - Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders. AB - The neurovascular unit (NVU) comprises brain endothelial cells, pericytes or vascular smooth muscle cells, glia and neurons. The NVU controls blood-brain barrier (BBB) permeability and cerebral blood flow, and maintains the chemical composition of the neuronal 'milieu', which is required for proper functioning of neuronal circuits. Recent evidence indicates that BBB dysfunction is associated with the accumulation of several vasculotoxic and neurotoxic molecules within brain parenchyma, a reduction in cerebral blood flow, and hypoxia. Together, these vascular-derived insults might initiate and/or contribute to neuronal degeneration. This article examines mechanisms of BBB dysfunction in neurodegenerative disorders, notably Alzheimer's disease, and highlights therapeutic opportunities relating to these neurovascular deficits. PMID- 22048066 TI - Electrochemical sensor for neurotransmitters at physiological pH using a heterocyclic conducting polymer modified electrode. AB - We report the simultaneous determination of two neurotransmitters, norepinephrine (NEP) and serotonin (5-HT), at physiological pH using the electropolymerized film of 3-amino-5-mercapto-1,2,4-triazole modified glassy carbon (p-AMTa) electrode. A bare glassy carbon (GC) electrode fails to resolve the voltammetric signals of NEP and 5-HT due to the surface fouling caused by the oxidized products of them. However, the p-AMTa electrode not only separates the voltammetric signals of NEP and 5-HT with a potential difference of 150 mV between NEP and 5-HT but also shows higher oxidation currents for them. The simultaneous determination of NEP and 5-HT was successfully achieved at p-AMTa electrode using differential pulse voltammetry method. The amperometric current response increased linearly with increasing NEP and 5-HT concentration in the range of 1.0 * 10(-8) to 1.0 * 10( 4) M and 1.0 * 10(-8) to 5.0 * 10(-5) M, respectively, and the detection limit was found to be 1.65 * 10(-11) for NEP and 1.32 * 10(-11) M for 5-HT (S/N = 3). The p-AMTa electrode shows better recovery results for spiked NEP and 5-HT in human blood plasma samples. PMID- 22048067 TI - The pearls and pitfalls of magnetic resonance imaging for the spine. AB - Musculoskeletal imaging of the spine can be an invaluable tool to inform clinical decision making in patients with spinal pain. An understanding of the technology involved in producing and interpreting high-resolution images produced from magnetic resonance imaging (MRI) of the human spine is necessary to better appreciate which sequences can be used for, or tailored to, individual patients and their conditions. However, there is substantial variability in the clinical meaningfulness of some MRI findings of spinal tissues. For example, normal variants can often mimic significant musculoskeletal pathology, which could increase the risk of misinformed clinical decisions and, even worse, poor or adverse outcomes. This clinical commentary will highlight some of the pearls and pitfalls of MRI for the cervical, thoracic, and lumbar regions, and include cases to illustrate some of the common imaging artifacts and normal variants for MRI of the spine. PMID- 22048068 TI - Pathological correlates of gastrointestinal dysfunction in Parkinson's disease. AB - Gastrointestinal dysfunction is a prominent manifestation of Parkinson's disease (PD). Gastrointestinal symptoms in PD include reduced salivation, dysphagia, impaired gastric emptying, constipation, and defecatory dysfunction. Constipation may precede the development of somatic motor symptoms of PD for several years. Neuropathological studies show early accumulation of abnormal alpha-synuclein (alpha-SYN) containing inclusions (Lewy neurites) in the enteric nervous system (ENS) and dorsal motor nucleus of the vagus (DMV) both in PD and in incidental Lewy body disease (ILBD). These findings provided the basis for the hypothesis that alpha-SYN pathology progresses in a centripetal, prion-like fashion, from the ENS to the DMV and then to more rostral areas of the central nervous system. Colonic biopsies may show accumulation alpha-SYN immunoreactive Lewy neurites in the submucosal plexus of PD patients. Salivary gland involvement is prominent in PD and alpha-SYN pathology can be detected both at autopsy and in minor salivary gland biopsies. PMID- 22048069 TI - Key factors determining the efficacy of gene therapy for continuous DOPA delivery in the Parkinsonian brain. AB - L-DOPA is currently the standard treatment for alleviating the motor symptoms in Parkinson's disease. The therapeutic efficacy, however, diminishes as the disease progresses. It has been suggested that the beneficial effect of L-DOPA could be reestablished by changing the mode of administration. Indeed, continuous delivery of l-DOPA has been shown to be an effective way to circumvent many of the side effects seen with traditional oral administration, which results in an intermittent supply of the dopamine precursor to the brain. However, all currently tested continuous dopaminergic stimulation approaches rely on peripheral administration. This is not ideal since it gives rise to off target effects and is difficult to maintain long-term. Thus, there is an unmet need for an effective continuous administration method with an acceptable side effect profile. Viral-mediated gene therapy is a promising alternative paradigm that can meet this demand. Encouraging preclinical studies in animal models of Parkinson's disease showed therapeutic efficacy after expression of the genes encoding the enzymes required for biosynthesis of dopamine. Although the first phase I clinical trials using these approaches have been conducted, clear positive data in placebo controlled efficacy studies is still lacking. We are now at a critical junction and need to carefully review the preclinical data from the clinical translation perspective and identify the key factors that will determine the potential for success in gene therapy for Parkinson's disease. PMID- 22048070 TI - Flare-up of previously quiescent chronic osteomyelitis 20 years after childhood skeletal traction: a report of two cases. AB - Management of lower limb fractures in children involves many approaches, spanning from conservative treatment to open reduction and internal fixation. A number of intermediate treatments have also been shown to be effective, notably skeletal traction. However, each of these techniques has its own advantages and disadvantages in terms of complications. In this report, we describe two new cases of chronic osteomyelitis that manifested (many years) after childhood skeletal traction. After analysing these two cases, we proposed measures that can be implemented to avoid such complications, along with a simple, appropriate, reproducible treatment approach. PMID- 22048071 TI - Palladium-catalysed cross-coupling of organosilicon reagents. AB - The palladium catalysed cross-coupling of organosilicon reagents with organo halides and pseudo-halides has developed over the past 30 years into an efficient and attractive carbon-carbon bond forming strategy. Extensive research within this field to expand and diversify on the scope of the organosilicon coupling reaction will continue to promote its use in the synthesis of biologically and pharmaceutically important organic molecules. The recent advances made within this area are explored in this critical review (199 references). PMID- 22048089 TI - Arthroscopic rotator cuff repair with and without acromioplasty in the treatment of full-thickness rotator cuff tears: a multicenter, randomized controlled trial. AB - BACKGROUND: The primary objective of this prospective randomized controlled trial was to compare functional and quality-of-life indices and rates of revision surgery in arthroscopic rotator cuff repair with and without acromioplasty. METHODS: Eighty-six patients consented and were randomly assigned intraoperatively to one of two study groups, and sixty-eight of them completed the study. The primary outcome was the Western Ontario Rotator Cuff (WORC) index. Secondary outcome measures included the American Shoulder and Elbow Surgeons (ASES) shoulder assessment form and a count of revisions required in each group. Outcome measures were completed preoperatively and at three, six, twelve, eighteen, and twenty-four months after surgery. RESULTS: WORC and ASES scores improved significantly in each group over time (p < 0.001). There were no differences in WORC or ASES scores between the groups that had arthroscopic cuff repair with or without acromioplasty at any time point. There were no differences in scores on the basis of acromion type, nor were any interaction effects identified between group and acromion type. Four participants (9%) in the group that had arthroscopic cuff repair alone, one with a Type-2 and three with a Type 3 acromion, required additional surgery by the twenty-four-month time point. The number of patients who required additional surgery was greater (p = 0.05) in the group that had arthroscopic cuff repair alone than in the group that had arthroscopic cuff repair and acromioplasty. CONCLUSIONS: Our findings are consistent with previous research reports in which there was no difference in functional and quality-of-life indices for patients who had rotator cuff repair with or without acromioplasty. The higher reoperation rate was found in the group without acromioplasty. Further study that includes follow-up imaging and patient reported outcomes over a greater follow-up period is needed. PMID- 22048090 TI - Temperature-sensitive release of prostaglandin E2 and diminished energy requirements in synovial tissue with postoperative cryotherapy: a prospective randomized study after knee arthroscopy. AB - BACKGROUND: Local external cooling of the surgical field after joint surgery is intended to enhance recovery and to facilitate the use of outpatient surgery by reducing pain and improving mobility. We hypothesized that the effects of postoperative cooling and compression after knee arthroscopy would be reflected in changes in the concentrations of metabolic and inflammatory markers in the synovial membrane. METHODS: Forty otherwise healthy patients who were to undergo knee arthroscopy were included in the study, and half were randomized to receive postoperative cooling and compression. Microdialysis of the synovial membrane was performed postoperatively, and the concentrations of prostaglandin E2 (PGE2), glucose, lactate, glycerol, and glutamate as well as the ethanol exchange ratio (which indicates blood flow) were measured. The temperature of the knee was monitored, and postoperative pain was assessed by the patient with use of a visual analog scale, a numeric rating scale, and the need for rescue medication. RESULTS: Application of the cooling and compression device after knee arthroscopy significantly lowered the temperature in the operatively treated knee (as measured on the skin, within the joint capsule, and intra-articularly). The cooling and compression appeared to decrease inflammation, as indicated by a temperature-sensitive decrease in the PGE2 concentration. The hypothermia also decreased the metabolic rate of the synovial tissue and thus decreased energy requirements, as shown by the stability of the lactate concentration over time despite the decreased blood flow that was indicated by the increasing ethanol exchange ratio. No effect of the compression and cooling on postoperative pain was detected. CONCLUSIONS: Local cryotherapy and compression after knee arthroscopy significantly lowered the temperature in the knee postoperatively, and the synovial PGE2 concentration was correlated with the temperature. Since PGE2 is a marker of pain and inflammation, the postoperative local cooling and compression appeared to have a positive anti-inflammatory effect. PMID- 22048091 TI - The effect of three-component total ankle replacement malalignment on clinical outcome: pain relief and functional outcome in 317 consecutive patients. AB - BACKGROUND: Total ankle replacement has become an increasingly popular treatment for patients with end-stage ankle osteoarthritis. The surgery is technically demanding and generally performed by only experienced foot and ankle surgeons. An important complication of total ankle replacement is malposition of the talar component. The biomechanical effect of malposition has been reported; however, the functional outcomes of patients with varying degrees of talar component malposition have not. The purpose of this study was to assess the influence of talar component malposition on postoperative pain relief and functional outcome. METHODS: This retrospective cohort study included 317 total ankle replacements in 317 patients. The anteroposterior offset ratio was measured with use of lateral ankle radiographs made with the patient in a standing, weight-bearing position. Patients were classified into one of three groups: those with an anteroposterior offset ratio of 0 (127 ankles), those with a ratio of >0 (103 ankles), and those with a ratio of <0 (eighty-seven ankles). Postoperative pain relief was assessed with use of a visual analogue scale. Functional outcome was assessed with the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score and measurement of ankle range of motion. The mean duration of follow-up (and standard deviation) was 53.2 +/- 18.4 months (range, twenty-four to ninety-eight months). RESULTS: The postoperative pain level in the group with an anteroposterior offset ratio of 0 was significantly lower than that for both the group with a ratio of >0 (p < 0.001) and the group with a ratio of <0 (p = 0.017). Also, the functional outcome, measured with use of the AOFAS hindfoot score, was significantly higher, and ankle motion was significantly greater, in the group with an anteroposterior offset ratio of 0 than in the group with a ratio of >0 (p = 0.003 and p < 0.001, respectively) and the group with a ratio of <0 (p = 0.007 and p = 0.080). CONCLUSIONS: The anteroposterior offset ratio may be a useful predictor of outcome in patients with total ankle replacement with regard to both pain and function. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 22048092 TI - Revision surgery following operations for lumbar stenosis. AB - BACKGROUND: For carefully selected patients with lumbar stenosis, decompression surgery is more efficacious than nonoperative treatment. However, some patients undergo repeat surgery, often because of complications, the failure to achieve solid fusion following arthrodesis procedures, or persistent symptoms. We assessed the probability of repeat surgery following operations for the treatment of lumbar stenosis and examined its association with patient age, comorbidity, previous surgery, and the type of surgical procedure. METHODS: We performed a retrospective cohort analysis of Medicare claims. The index operation was performed in 2004 (n = 31,543), with follow-up obtained through 2008. Operations were grouped by complexity as decompression alone, simple arthrodesis (one or two disc levels and a single surgical approach), or complex arthrodesis (more than two disc levels or combined anterior and posterior approach). Reoperation rates were calculated for each follow-up year, and the time to reoperation was analyzed with proportional hazards models. RESULTS: The probability of repeat surgery fell with increasing patient age or comorbidity. Aside from age, the strongest predictor was previous lumbar surgery: at four years the reoperation rate was 17.2% among patients who had had lumbar surgery prior to the index operation, compared with 10.6% among those with no prior surgery (p < 0.001). At one year, the reoperation rate for patients who had been managed with decompression alone was slightly higher than that for patients who had been managed with simple arthrodesis, but by four years the rates for these two groups were identical (10.7%) and were lower than the rate for patients who had been managed with complex arthrodesis (13.5%) (p < 0.001). This difference persisted after adjusting for demographic and clinical features (hazard ratio for complex arthrodesis versus decompression 1.56, 95% confidence interval, 1.26 to 1.92). A device-related complication was reported at the time of 29.2% of reoperations following an initial arthrodesis procedure. CONCLUSIONS: The likelihood of repeat surgery for spinal stenosis declined with increasing age and comorbidity, perhaps because of concern for greater risks. The strongest clinical predictor of repeat surgery was a lumbar spine operation prior to the index operation. Arthrodeses were not significantly associated with lower rates of repeat surgery after the first postoperative year, and patients who had had complex arthrodeses had the highest rate of reoperations. PMID- 22048093 TI - Chronic opioid use prior to total knee arthroplasty. AB - BACKGROUND: Chronic use of opioid medications may lead to dependence or hyperalgesia, both of which might adversely affect perioperative and postoperative pain management, rehabilitation, and clinical outcomes after total knee arthroplasty. The purpose of this study was to evaluate patients who underwent total knee arthroplasty following six or more weeks of chronic opioid use for pain control and to compare them with a matched group who did not use opioids preoperatively. METHODS: Forty-nine knees in patients who had a mean age of fifty-six years (range, thirty-seven to seventy-eight years) and who had regularly used opioid medications for pain control prior to total knee arthroplasty were compared with a group of patients who had not used them. Length of hospitalization, aseptic complications requiring reoperation, requirement for specialized pain management, and clinical outcomes were assessed for both groups. RESULTS: Knee Society scores were significantly lower in the patients who regularly used opioid medications at the time of final follow-up (mean, three years; range, two to seven years); the opioid group had a mean of 79 points (range, 45 to 100 points) as compared with a mean of 92 points (range, 59 to 100 points) in the non-opioid group. A significantly higher prevalence of complications was seen in the opioid group, with five arthroscopic evaluations and eight revisions for persistent stiffness and/or pain, compared with none in the matched group. Ten patients in the opioid group were referred for outpatient pain management, compared with one patient in the non-opioid group. CONCLUSIONS: Patients who chronically use opioid medications prior to total knee arthroplasty may be at a substantially greater risk for complications and painful prolonged recoveries. Alternative non-opioid pain medications and/or earlier referral to an orthopaedic surgeon prior to habitual opioid use should be considered for patients with painful degenerative disease of the knee. PMID- 22048094 TI - Use of the Sheffield telescopic intramedullary rod system for the management of osteogenesis imperfecta: clinical outcomes at an average follow-up of nineteen years. AB - BACKGROUND: Elongating intramedullary rods have been used in the management of osteogenesis imperfecta for the past fifty years. The complication rates reported in many reviews of the available techniques have been high. This study reviews the long-term functional outcomes and complications following the use of the Sheffield system of telescopic intramedullary rods. METHODS: We conducted a retrospective analysis of patients with osteogenesis imperfecta who were at least eighteen years of age and who had at least thirteen years of follow-up. Complications, reoperations, and data from a disease-specific questionnaire and the Short Form-36 questionnaire were recorded. RESULTS: Data for twenty-two patients with osteogenesis imperfecta who had been treated with Sheffield telescopic intramedullary rods were available at an average of nineteen years after the initial surgery. Reoperations involving thirty-three (50%) of the sixty six rods were performed: ten rods (15%) were exchanged because of rod disengagement due to growth, thirteen rods (20%) were exchanged because of complications, and ten rods (15%) required further surgery other than exchange because of complications. Mobility was significantly improved at the initial postoperative visit (p = 0.0015), and this improvement was maintained into adulthood (p = 0.0077). Back pain was the most frequent symptom. Symptoms related to rod insertion across the knee and ankle were rare, but symptoms related to proximal femoral trochanteric entry were common. Physeal damage was not seen following surgery, and all rods elongated with growth. All patients were satisfied with the outcome of the surgical procedures. Short Form-36 scores for all physical domains and for social function and vitality were significantly worse than those in a normal population. CONCLUSIONS: The outcomes of this technique are satisfactory in adulthood; reoperation rates are high but are most commonly related to the patient outgrowing the rods. Concerns regarding insertion of this fixed device at the knee and ankle were unfounded, although proximal femoral fixation remains a problem. PMID- 22048095 TI - Prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) use for the treatment of infection after shoulder arthroplasty. AB - BACKGROUND: There are limited data on Prosthesis of Antibiotic-Loaded Acrylic Cement (PROSTALAC) use for the treatment of infection following shoulder arthroplasty. We performed a retrospective review of our experience with the PROSTALAC in terms of infection eradication, complications, and outcomes. METHODS: Twenty-eight patients with an infection at the site of a shoulder arthroplasty who were managed with the PROSTALAC were followed until eradication of the infection and maximum functional improvement. The average duration of follow-up was 27.6 months (range, twelve to sixty-nine months). In twenty-five of the twenty-eight patients, the PROSTALAC was created with antibiotic-impregnated cement, a standard humeral head mold, and a scaffold with either a one-third tubular plate or a 3.5-mm reconstruction plate. Three PROSTALAC implants had no scaffold. RESULTS: Although all patients benefited from the use of the PROSTALAC, there were nine complications in eight patients (29%), with six additional unplanned surgical procedures being performed in this group. One patient had a dislocation, three had a fracture of the PROSTALAC, and five had recurrent infections requiring debridement and revision PROSTALAC placement. All fractures were associated with use of the semitubular plate. Twelve patients (43%), including two with revision PROSTALAC implants, were satisfied with pain relief and function and declined a second-stage procedure. With the exclusion of two patients who had a revision PROSTALAC implant, sixteen patients (57%) had a second-stage procedure; the procedures included ten reverse shoulder arthroplasties, three hemiarthroplasties, two total shoulder arthroplasties, and one resection arthroplasty. At the time of the latest follow-up, the average forward elevation of the shoulder was 77 degrees (range, 30 degrees to 130 degrees ). Fifteen patients had no or mild pain, eight patients had moderate pain, and five had severe pain. Patients with reverse total shoulder arthroplasties did not have improved function compared with the other cohorts. CONCLUSIONS: The use of the PROSTALAC for the treatment of infection following shoulder arthroplasty is beneficial. Infection was initially eradicated in twenty three (82%) of twenty-eight patients, more than half of our patients had mild or no pain, and 43% of patients declined a second-stage procedure because of acceptable function and pain relief. Conversely, five of twenty-eight patients had severe pain and five patients had persistent infection requiring additional surgery. The use of the reverse total shoulder arthroplasty did not appear to improve outcomes. PMID- 22048096 TI - Does physiologic posterolateral laxity influence clinical outcomes of anterior cruciate ligament reconstruction? AB - BACKGROUND: The purpose of this retrospective study was to evaluate the influence of physiologic posterolateral rotatory laxity on anterior cruciate ligament (ACL) reconstruction in terms of anterior knee stability and clinical outcomes. METHODS: We retrospectively studied 113 patients who had undergone ACL reconstruction between June 2004 and August 2008. Patients were categorized into three groups according to the degree of tibial external rotation at 90 degrees of knee flexion: Group 1 (<40 degrees ), Group 2 (40 degrees to 50 degrees ), and Group 3 (>=50 degrees ). Ligament stability was determined with use of the Lachman test, the pivot-shift test, and KT-2000 arthrometer testing. Function was assessed with use of the Lysholm score and the International Knee Documentation Committee (IKDC) score. Clinical outcomes were determined from data obtained before surgery and at the twenty-four-month follow-up visit. RESULTS: We observed differences in postoperative knee translation between the groups (p < 0.001). A post hoc test showed increased mean knee translation in Group 3 compared with Groups 1 and 2. The degree of external rotation at 90 degrees was positively correlated with anterior knee translation (r = 0.428; p = 0.007). However, there was an inverse correlation with the Lysholm knee scores (r = -0.146; p = 0.015) and IKDC scores (r = -0.205; p = 0.003). CONCLUSIONS: The stability and functional scores after ACL reconstruction had a negative correlation with the degree of external rotation of the tibia at 90 degrees (physiologic posterolateral rotatory laxity). After ACL reconstruction, patients with >= 50 degrees of tibial external rotation had increased anterior translation and worse functional outcomes in comparison with those who had < 50 degrees of tibial external rotation. PMID- 22048098 TI - The stabilizing effect of the distal interosseous membrane on the distal radioulnar joint in an ulnar shortening procedure: a biomechanical study. AB - BACKGROUND: The importance of the stabilizing effect of the distal interosseous membrane on the distal radioulnar joint, especially in patients with a distal oblique bundle, has been described. The purpose of this study was to evaluate the stability of the distal radioulnar joint after an ulnar shortening osteotomy and to quantify longitudinal resistance to ulnar shortening when the osteotomy was proximal or distal to the ulnar attachment of the distal interosseous membrane. These relationships were characterized for forearms with or without a distal oblique bundle. METHODS: Ten fresh-frozen cadavers were used. A transverse osteotomy and ulnar shortening was performed proximal (proximal shortening) and distal (distal shortening) to the ulnar attachment of the distal interosseous membrane. Distal radioulnar joint laxity was evaluated as the volar and dorsal displacements of the radius relative to the fixed ulna with 20 N of applied force. Testing was performed under controlled 1-mm increments of ulnar shortening up to 4 mm, with the forearm in neutral alignment, 60 degrees of pronation, and 60 degrees of supination. Resistance to ulnar shortening was quantified as the slope of the load-displacement curve obtained by displacing the distal ulnar segment proximally. RESULTS: In proximal shortening, significantly greater stability of the distal radioulnar joint was obtained with even 1 mm of shortening compared with the control, whereas distal shortening demonstrated significant improvement in stability of the distal radioulnar joint only after shortening of >=4 mm in all rotational positions. Significantly greater stability of the distal radioulnar joint was achieved with proximal shortening than with distal shortening and in specimens with a distal oblique bundle than in those without a distal oblique bundle. The longitudinal resistance to ulnar shortening was significantly greater in proximal shortening than in distal shortening. The stiffness in proximal shortening was not affected by the presence of a distal oblique bundle in the distal interosseous membrane. CONCLUSIONS: Ulnar shortening with the osteotomy carried out proximal to the attachment of the distal interosseous membrane had a more favorable effect on stability of the distal radioulnar joint compared with distal osteotomy, especially in the presence of a distal oblique bundle. PMID- 22048100 TI - Joint chondrolysis. AB - Although the disease was first described in the hip, reports of chondrolysis in nearly all diarthrodial joints have since emerged with considerable variations in the literature.Despite speculation among clinicians and researchers about the implicit causal pathways and etiologic contributors associated with chondrolysis, definitive answers remain elusive.The term chondrolysis has been applied to varied levels of joint cartilage destruction from focal chondral defects to diffuse cartilage loss, revealing a lack of consistency in the application of diagnostic criteria to guide differential disease classification.Differentiating between the various potential etiologies associated with chondrolysis provides opportunities for the prevention of the disease. PMID- 22048097 TI - Interobserver reliability of radial head fracture classification: two-dimensional compared with three-dimensional CT. AB - BACKGROUND: The Broberg and Morrey modification of the Mason classification of radial head fractures has substantial interobserver variation. This study used a large web-based collaborative of experienced orthopaedic surgeons to test the hypothesis that three-dimensional reconstructions of computed tomography (CT) scans improve the interobserver reliability of the classification of radial head fractures according to the Broberg and Morrey modification of the Mason classification. METHODS: Eighty-five orthopaedic surgeons evaluated twelve radial head fractures. They were randomly assigned to review either radiographs and two dimensional CT scans or radiographs and three-dimensional CT images to determine the fracture classification, fracture characteristics, and treatment recommendations. The kappa multirater measure (kappa) was calculated to estimate agreement between observers. RESULTS: Three-dimensional CT had moderate agreement and two-dimensional CT had fair agreement among observers for the Broberg and Morrey modification of the Mason classification, a difference that was significant. Observers assessed seven fracture characteristics, including fracture line, comminution, articular surface involvement, articular step or gap of >=2 mm, central impaction, recognition of more than three fracture fragments, and fracture fragments too small to repair. There was a significant difference in kappa values between three-dimensional CT and two-dimensional CT for fracture fragments too small to repair, recognition of three fracture fragments, and central impaction. The difference between the other four fracture characteristics was not significant. Among treatment recommendations, there was fair agreement for both three-dimensional CT and two-dimensional CT. CONCLUSIONS: Although three dimensional CT led to some small but significant decreases in interobserver variation, there is still considerable disagreement regarding classification and characterization of radial head fractures. Three-dimensional CT may be insufficient to optimize interobserver agreement. PMID- 22048101 TI - Factors associated with recurrence of primary aneurysmal bone cysts: is argon beam coagulation an effective adjuvant treatment? AB - BACKGROUND: Our goal was to assess the effectiveness and safety of argon beam coagulation as an adjuvant treatment for primary aneurysmal bone cysts, to reevaluate the adjuvant effectiveness of the use of a high-speed burr alone, and, secondarily, to identify predictors of aneurysmal bone cyst recurrence. METHODS: We retrospectively reviewed the records of ninety-six patients with primary aneurysmal bone cysts who were managed at our institution from January 1, 1983, to December 31, 2008. Forty patients were managed with curettage, a high-speed burr, and argon beam coagulation; thirty-four were managed with curettage and a high-speed burr without argon beam coagulation; and the remaining twenty-two were managed with curettage with argon beam coagulation alone, curettage with no adjuvant treatment, or resection of the entire lesion. Demographic, clinical, and radiographic data were viewed comparatively for possible predictors of recurrence. Kaplan-Meier survival analysis with a log-rank test was performed to measure association and effectiveness. RESULTS: The median age at the time of diagnosis was fifteen years (range, one to sixty-two years). The median duration of follow-up was 29.5 months (range, zero to 300 months). The overall rate of recurrence of aneurysmal bone cyst after surgical treatment was 11.5%. The rate of recurrence was 20.6% after curettage and high-speed-burr treatment alone and 7.5% after curettage and high-speed-burr treatment plus argon beam coagulation. The five-year Kaplan-Meier survival estimate was 92% for patients managed with curettage and adjuvant treatment with a high-speed burr and argon beam coagulation, compared with 73% for patients managed with curettage and a high speed burr only (p = 0.060). CONCLUSIONS: Surgical treatment of aneurysmal bone cyst with curettage and adjuvant argon beam coagulation is effective. Postoperative fracture appears to be a common complication of this treatment and needs to be studied further. Treatment with curettage and high-speed burr alone may not reduce recurrence. PMID- 22048102 TI - Change in the position of the popliteal artery with knee flexion after total knee arthroplasty: AAOS exhibit selection. PMID- 22048103 TI - Chondrolysis of the tibial plateau caused by articular aspergillosis after ACL autograft reconstruction: management with a fresh osteochondral allograft: a case report. PMID- 22048104 TI - Snapping of the proximal hamstring origin: a rare cause of coxa saltans: a case report. PMID- 22048105 TI - The disruptive orthopaedic surgeon: implications for patient safety and malpractice liability. AB - Disruptive physician behavior imperils patient safety, erodes the morale of other health care providers, and dramatically increases the risk of malpractice litigation. Increasing patient volume, decreasing physician reimbursement, malpractice litigation, elevated stress, and growing job dissatisfaction have been implicated in disruptive behavior, which has emerged as one of the major challenges in health care. Because the aging patient population relies increasingly on orthopaedic services to maintain quality of life, improving professionalism and eradicating disruptive behavior are urgent concerns in orthopaedic surgery. Although many steps have been taken by The Joint Commission to improve patient care and define disruptive behavior, there is further room for improvement by physicians. Barriers to eliminating disruptive behavior by orthopaedic surgeons include fear of retaliation, lack of awareness among the surgeon's peers, and financial factors. Surgeons have a duty to address patterns of negative peer behavior for the benefit of patient care. This manuscript addresses the causes and consequences of disruptive physician behavior as well as management strategies, especially in orthopaedic surgery. PMID- 22048106 TI - Arthroscopic basic task performance in shoulder simulator model correlates with similar task performance in cadavers. AB - BACKGROUND: Attainment of the technical skill necessary to safely perform arthroscopic procedures requires the instruction of orthopaedic surgery residents in basic arthroscopic skills. Although previous studies involving shoulder arthroscopy simulators have demonstrated a correlation between task performance and the level of prior arthroscopic experience, data demonstrating the correlation of simulator performance with arthroscopic skill in a surgical setting are scarce. Our goal was to evaluate the correlation between timed task performance in an arthroscopic shoulder simulator and timed task performance in a cadaveric shoulder arthroscopy model. METHODS: Subjects were recruited from among residents and attending surgeons in an orthopaedic surgery residency program. Each subject was tested on an arthroscopic shoulder simulator and objectively scored on the basis of the time taken to complete a standardized object selection program. After an interval of at least two weeks, each subject was then tested on a cadaveric shoulder arthroscopy model designed to replicate the shoulder arthroscopy simulator testing protocol, and the time to completion was again recorded. Both testing protocols involved the simple task of placing a probe on a series of assigned locations in the glenohumeral joint. Spearman rank correlation analysis was performed, and regression analysis was used to determine the predictive ability of the simulator score. RESULTS: The performance time on the simulation program was strongly correlated with the performance time on the cadaveric model (r = 0.736, p < 0.001). The time required to complete the simulator task was a significant predictor of the time required to complete the cadaveric task (t = 4.48, p < 0.001). CONCLUSIONS: These results demonstrated a strong correlation between performance of basic arthroscopic tasks in a simulator model and performance of the same tasks in a cadaveric model. PMID- 22048107 TI - Can statistics alone add clinical meaning to non-specific billing databases? Commentary on an article by Richard A. Deyo, MD, MPH, et al.: "Revision surgery following operations for lumbar stenosis". PMID- 22048108 TI - Preoperative pain management decisions impact outcome after total knee arthroplasty-implications for opiate use: commentary on an article by Michael G. Zywiel, MD, et al.: "Chronic opioid use prior to total knee arthroplasty". PMID- 22048109 TI - Immunogenicity, reactogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Mexican infants. AB - The immunogenicity and safety of the 10-valent pneumococcal conjugate vaccine, PHiD-CV, have been documented in European and Asian studies. In this open study conducted in Mexico (NCT00489554), 230 healthy infants received three doses of PHiD-CV and DTPa-HBV-IPV/Hib vaccines at 2, 4 and 6 months of age and two doses of oral human rotavirus vaccine at 2 and 4 months. Serotype-specific pneumococcal responses and opsonophagocytic activity (OPA) were measured one month post-dose 3. PHiD-CV's primary vaccination course was highly immunogenic against each of the 10 pneumococcal vaccine serotypes and carrier protein D. Antibody responses against pneumococcal serotypes and protein D were generally higher in Mexican infants compared with European antibody responses, and functional OPA responses were also higher or in the same range. The most frequent solicited local symptom was pain, with high but similar incidences of grade 3 pain reported at both injection sites (up to 15% of all doses). PHiD-CV was well tolerated, with no serious adverse events considered as causally related to vaccination. Most solicited symptoms were mild and there was no increase in incidence of solicited symptoms with successive vaccine doses. PMID- 22048110 TI - Safety and tolerability of zoster vaccine in adults >=60 years old. AB - OBJECTIVE: To evaluate the general safety of zoster vaccine (ZV) in adults >=60 years old. PATIENTS/METHODS: Subjects were enrolled in a 1:1 ratio to receive 1 dose of ZV or placebo. Subjects were followed for serious adverse experiences (SAEs) for 42 days (primary follow-up period) and 182 days (secondary follow-up period) postvaccination. Relative-risks (ZV/placebo) for SAEs during both safety periods were calculated. STUDY PERIOD: 17-Sep-2007 to 09-Jan-2009. RESULTS: Overall, 5,983 subjects received ZV and 5,997 received placebo. Within the primary 42-day follow-up period, 84 ZV subjects and 67 placebo subjects reported SAEs. The estimated risk of SAEs within 42 days was 1.41% for ZV versus 1.12% for placebo, with a relative-risk of 1.26 (95% CI 0.91,1.73); indicating no statistically significant difference between groups, meeting the pre-specified success criterion. During the 182-day follow-up period, 340 ZV subjects and 300 placebo subjects reported SAEs. The estimated risk of SAEs within 182 days was 5.68% for ZV versus 5.01% for placebo, with a relative-risk of 1.13 (95% CI 0.98,1.32), indicating no statistically significant difference between groups. Two subjects in the ZV group reported SAEs deemed by the investigator to be vaccine-related (uveitis and sciatica; onset Day 5 and 4, respectively). One subject in the placebo group reported a SAE deemed by the investigator to be vaccine-related (lumbar radiculopathy; onset Day 51). There were 24 fatal SAEs in the ZV group and 17 in the placebo group (relative risk = 1.41; CI: 0.77, 2.60); 6 and 5, respectively, with SAE onset during the primary 42-day follow-up period. No deaths were deemed vaccine-related. CONCLUSIONS: ZV and placebo groups had similar safety profiles in terms of SAEs during the primary (Day 1 to 42) and secondary (Day 1 to 182) follow-up periods. PMID- 22048111 TI - Recombinant vaccines against leptospirosis. AB - Leptospirosis is an important neglected infectious disease that occurs in urban environments, as well as in rural regions worldwide. Rodents, the principal reservoir hosts of pathogenic Leptospira spp., and other infected animals shed the bacteria in their urine. During occupational or even recreational activities, humans that come into direct contact with infected animals or with a contaminated environment, particularly water, are at risk of infection. Prevention of urban leptospirosis is largely dependent on sanitation measures that are often difficult to implement, especially in developing countries. Vaccination with inactivated whole-cell preparations (bacterins) has limited efficacy due to the wide antigenic variation of the pathogen. Intensive efforts towards developing improved recombinant vaccines are ongoing. During the last decade, many reports on the evaluation of recombinant vaccines have been published. Partial success has been obtained with some surface-exposed protein antigens. The combination of protective antigens and new adjuvants or delivery systems may result in the much needed effective vaccine. PMID- 22048112 TI - Rural parents' vaccination-related attitudes and intention to vaccinate middle and high school children against influenza following educational influenza vaccination intervention. AB - OBJECTIVE: This study examined changes in parental influenza vaccination attitudes and intentions after participating in school-based educational influenza vaccination intervention. METHODS: Participants were drawn from three counties participating in a school-based influenza vaccination intervention in rural Georgia (baseline N=324; follow-up N=327). Data were collected pre- and post-intervention from phone surveys with parents' with children attending middle and high-school. Attitudes, beliefs, vaccination history, and intention to vaccinate were assessed. RESULTS: Parents who participated in the intervention conditions reported significantly higher influenza vaccination rates in their adolescents, relative to a control group, as well as increased vaccination rates post-intervention participation relative to their baseline rates. Intervention participants reported greater intention to have their adolescent vaccinated in the coming year compared to control parents. Significant differences were observed post intervention in perceived barriers and benefits of vaccination. CONCLUSIONS: These findings suggest that a school-delivered educational influenza vaccination intervention targeting parents and teens may influence influenza vaccination in rural communities. Future influenza vaccination efforts geared toward the parents of rural middle- and high-school students may benefit from addressing barriers and benefits of influenza vaccination. PMID- 22048113 TI - Relationship of therapeutic cancer vaccine development to population disease burden and five-year survival. AB - In the United States, therapeutic vaccines may provide considerable benefit to cancer patients. Yet, there has been no assessment of whether vaccines currently in the research and development pipeline reflect the burden of disease and current survival patterns for different malignancies. The authors used data from the National Cancer Institute, Surveillance Epidemiology and End Results (SEER) database, and clinicaltrials.gov registry to characterize the vaccine development pipeline with respect to 5 measures of disease burden and treatment effectiveness for cancer: annual incidence, annual mortality, five-year survival rate, recent change in five-year survival (1999-2006 vs 1990-1992), and five-year mortality estimate (=annual incidence*[1 - 5-yr survival rate]). In 2011, the authors identified 231 active clinical trials for therapeutic cancer vaccines. Of these trials, 81 vaccines are currently in Phase I, 140 in Phase II, and 10 vaccines in Phase III. Vaccine trials for melanoma are most common (n=40), followed by breast cancer (34), lung cancer (30), and prostate cancer (22). Correlation analyses revealed that only annual cancer incidence is significantly associated with current therapeutic cancer vaccine trial activity (r=.60; p=.003). Annual mortality, 5-year survival rate and 5-year mortality estimates were not associated with vaccine trial activity. The authors conclude that therapeutic cancer vaccine clinical trials correspond with disease incidence in the U.S., but not with measures of mortality and survival that reflect the effectiveness of currently available treatment modalities. Future development of therapeutic vaccines for cancer may benefit patients more if there is stronger complementarity with other therapeutic options. PMID- 22048114 TI - Candida vaccines development from point view of US patent application. AB - Candidiasis is the fourth most common bloodstream infection in hospitalized patients in the United States. Moreover, the mortality rate from Candida infections remains high, even after treatment with antifungal therapy. Vaccination would be a promising strategy for prevention of invasive fungal infections. In order to examine the main trends in anticandidal vaccine patenting activity, we conducted an analysis for anticandidal vaccine patents. We find 190 issued patent and 940 patent application documents containing the keywords Candida and vaccine within claims in the USA. Candida vaccines development, as evidenced by the numbers of issued patents, has decreased since the year 2002. Furthermore, the number of patent applications in Candida vaccines may indicate the strength of engaged resources were also in the status of stagnation during 2005-2007 and even a decline in 2008. Academic and nonprofit research institutions not only account for a large share of Candida vaccines patents but also apply for patents continually. Based on this analysis, the strength of Candida vaccines resources seems to remain stagnant in recent years due to patent prosecution or technical barrier in the filed of Candida vaccines. Therefore, we consider that Candida vaccines technology to still be under development and the researchers are still looking for scientific breakthrough in the filed. PMID- 22048115 TI - A novel adjuvant Ling Zhi-8 for cancer DNA vaccines. AB - DNA vaccines have a wide range of applications, with several potential advantages compared to other vaccine technologies for diseases. No DNA vaccine has yet been licensed in humans; however, a lot of effort has been made to enhance their potential as human vaccines and therapeutics. Finding an effective adjuvant is a strategy to improve the efficacy of DNA vaccines. We recently identified a fungal immunomodulatory protein Ling Zhi-8 (LZ-8) with stimulatory activity on dendritic cells (DCs) that significantly increases the efficacy of a cancer DNA vaccine in a preclinical tumor model, suggesting that LZ-8 may be a good candidate adjuvant for vaccine development. Here we discuss the possibility for applying LZ-8 to a cancer DNA vaccine for humans. PMID- 22048116 TI - Leishmaniasis. AB - Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. WHO has classified the disease as emerging and uncontrolled and estimates that the infection results in two million new cases a year. There are 12 million people currently infected worldwide, and leishmaniasis threatens 350 million people in 88 countries. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. However, to date, no such vaccine is available despite substantial efforts by many laboratories. Main obstacle in vaccine design is the transition from the laboratory to the field and extrapolation of data from animal models to humans. This review discusses recent findings in the antileishmania vaccine field and current difficulties hampering vaccine implementation. PMID- 22048117 TI - Buruli ulcer. AB - Buruli Ulcer (BU) is a neglected, necrotizing skin disease, caused by M. ulcerans, that can leave patients with prominent scars and lifelong disability. M. ulcerans produces a diffusible lipid toxin, mycolactone, essential for bacterial virulence. Prevention is difficult as little is known about disease transmission and there is no vaccine. There have been several recent advances in the field. These include sequencing of the bacterial genome and of the giant plasmid responsible for mycolactone synthesis, better understanding of the bacterial lifecycle and of the mechanism of action of the toxin. This work has revealed a number of possible vaccine candidates, some of which are shared with other mycobacteria, e.g. M. tuberculosis, while other targets are unique to M. ulcerans. In this review, we discuss several M. ulcerans vaccine targets and vaccination methods, and outline some of the gaps in our understanding of the bacterium and the immune response against it. PMID- 22048118 TI - Haemophilus influenzae type b (Hib) vaccine: an effective control strategy in India. AB - Haemophilus influenzae type b (Hib) is an encapsulated, non-motile and non-spore forming Gram-negative coccobacillus which causes severe pneumonia, meningitis and other life threatening illnesses. Hib disease affects almost exclusively (95%) children aged less than 5 years throughout the world. The mean age of onset is 6 24 months after which it declines gradually until age 5 years. The World Health Organization (WHO) estimates that Hib is responsible for 3 million cases of serious illnesses and approximately 386,000 deaths worldwide each year in children aged under 5 years. In the latest position paper on Hib vaccine, WHO recommended the inclusion of Hib conjugate vaccines in all routine infant immunization programs without waiting for local disease-burden data. The WHO and the Global Alliance for Vaccine Immunization (GAVI) have been working to expand supplies of Hib vaccine, reduce vaccine cost, and assist especially low-income countries with vaccine introduction. Hib vaccine is safe, highly effective and readily available in the market. Hib vaccine has been shown to be > 95% efficacious in diverse populations around the world. Globally, hundreds of millions of doses of Hib vaccine have been administered in the last 2 decades. More than 160 countries are using Hib vaccine in national immunization programmes and around 25 countries planning to introduce. Hib vaccination fits into the India's national immunization schedule. PMID- 22048119 TI - H. pylori vaccines: why we still don't have any. AB - Helicobacter pylori was appreciated as the major cause of peptic ulcers about 30 years ago and the most significant etiological agent in gastric cancer in the mid 1990s. Since that time, progress in the development of a preventive or therapeutic H. pylori vaccine has been relatively slow. The impediments to rapid advances in the field include a luke-warm enthusiasm among clinicians, research scientists, and public health authorities concerning the need for a vaccine, rudimentary understanding of the correlates of gastric immunity to H. pylori and of gastric mucosal immunology in general, the geographical heterogeneity of the H. pylori genome and insufficient pharmaceutical industry support. Recent enhancements in our understanding of the gastric immune response together with advances in H. pylori genomics now provide the potential to accelerate progress in H. pylori vaccine development. Whether an H. pylori vaccine becomes a reality will likely depend upon our ability to appropriately target the populations at highest risk of the adverse sequelae of infection. PMID- 22048120 TI - Schistosomiasis vaccines. AB - Schistosomiasis is a major neglected tropical disease of public health importance to a billion people. An estimated 200 million people are currently infected; an additional 779 million individuals are at risk to acquire the infection in 74 countries. Despite many years of implementation of mass anti-parasitic drug therapy programs and other control measures, this disease has not been contained and continues to spread to new geographic areas. The discovery of a protective vaccine still remains the most potentially effective means for the control of this disease, especially if the vaccine provides long-term immunity against the infection. A vaccine would contribute to the reduction of schistosomiasis morbidity through induced immune responses leading to decrease in parasite load and reduced egg production. This vaccine could be administered to children between the ages of 3 and 12 years to prevent severe infection in a particularly high risk population. This review summarizes the current status of schistosomiasis vaccine development. PMID- 22048121 TI - Advances and challenges towards a vaccine against Chagas disease. AB - Chagas disease is major public health problem, affecting nearly 10 million people, characterized by cardiac alterations leading to congestive heart failure and death of 20-40% of the patients infected with Trypanosoma cruzi, the protozoan parasite responsible for the disease. A vaccine would be key to improve disease control and we review here the recent advances and challenges of a T. cruzi vaccine. There is a growing consensus that a protective immune response requires the activation of a Th1 immune profile, with the stimulation of CD8 (+) T cells. Several vacines types, including recombinant proteins, DNA and viral vectors, as well as heterologous prime-boost combinations, have been found immunogenic and protective in mouse models, providing proof-of-concept data on the feasibility of a preventive or therapeutic vaccine to control a T. cruzi infection. However, several challenges such as better end-points, safety issues and trial design need to be addressed for further vaccine development to proceed. PMID- 22048123 TI - In vivo P2X7 inhibition reduces amyloid plaques in Alzheimer's disease through GSK3beta and secretases. AB - beta-Amyloid (Abeta) peptide production from amyloid precursor protein (APP) is essential in the formation of the beta-amyloid plaques characteristic of Alzheimer's disease. However, the extracellular signals that maintain the balance between nonpathogenic and pathologic forms of APP processing, mediated by alpha secretase and beta-secretase respectively, remain poorly understood. In the present work, we describe regulation of the processing of APP via the adenosine triphosphate (ATP) receptor P2X7R. In 2 different cellular lines, the inhibition of either native or overexpressed P2X7R increased alpha-secretase activity through inhibition of glycogen synthase kinase 3 (GSK-3). In vivo inhibition of the P2X7R in J20 mice, transgenic for mutant human APP, induced a significant decrease in the number of hippocampal amyloid plaques. This reduction correlated with a decrease in glycogen synthase kinase 3 activity in J20 mice, increasing the proteolytic processing of APP through an increase in alpha-secretase activity. The in vivo findings presented here demonstrate for the first time the therapeutic potential of P2X7R antagonism in the treatment of familiar Alzheimer's disease (FAD). PMID- 22048122 TI - Advances and hurdles on the way toward a leprosy vaccine. AB - Prevalence rates for leprosy have declined sharply over the past 20 y, with this decline generally attributed to the WHO multi-drug therapy (MDT) campaign to provide free-of-charge treatment to all diagnosed leprosy patients. The success of this program appears to have reached its nadir, however, as evidenced by the stalled decreases in both global prevalence and new case detection rates of leprosy. Mass BCG vaccination for the prevention of tuberculosis (TB) at national levels has had a positive effect on leprosy decline and is often overlooked as an important factor in current leprosy control programs. Because BCG provides incomplete protection against both TB and leprosy, newer more effective TB vaccines are being developed. The impact that application of these vaccines will have on current leprosy control programs is unclear. In this review, we assess the need for vaccines within leprosy control programs. We summarize and discuss leprosy vaccine strategies that have been deployed previously and discuss those strategies that are currently being developed to augment recent breakthroughs in leprosy control. PMID- 22048124 TI - Cerebrovascular disease, beta-amyloid, and cognition in aging. AB - The present study evaluated cerebrovascular disease (CVD), beta-amyloid (Abeta), and cognition in clinically normal elderly adults. Fifty-four participants underwent magnetic resonance imaging (MRI), Pittsburgh compound B (PIB)-positron emission tomography (PET) imaging, and neuropsychological evaluation. High white matter hyperintensity burden and/or presence of infarct defined CVD status (CVD-: n = 27; CVD+: n = 27). PIB-positron emission tomography ratios of Abeta deposition were extracted using Logan plotting (cerebellar reference). Presence of high levels of Abeta in prespecified regions determined PIB status (PIB-: n = 33; PIB+: n = 21). Executive functioning and episodic memory were measured using composite scales. CVD and Abeta, defined as dichotomous or continuous variables, were unrelated to one another. CVD+ participants showed lower executive functioning (p = 0.001) when compared with CVD- individuals. Neither PIB status nor amount of Abeta affected cognition (ps >= 0.45), and there was no statistical interaction between CVD and PIB on either cognitive measure. Within this spectrum of normal aging CVD and Abeta aggregation appear to be independent processes with CVD primarily affecting cognition. PMID- 22048125 TI - Abeta-induced formation of autophagosomes is mediated by RAGE-CaMKKbeta-AMPK signaling. AB - Pathological autophagic vacuoles (AVs) accumulate in the brains of Alzheimer's disease (AD) patients, but the mechanisms by which they are induced are unknown. In this study, we found that the formation of AVs was mediated by activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in the brains of APP/PS1 double transgenic mice, amyloid-beta peptide (Abeta) pathology-bearing model mouse. Injection of sunitinib malate, AMPK inhibitor, to the mice lowered AV formation in their brains. Consistent with our in vivo observations, treatment of SH-SY5Y cells with Abeta enhanced the induction of autophagosomes, which was mediated by Ca(2+)/calmodulin-dependent protein kinase kinase-beta (CaMKKbeta) AMPK signaling, as shown using various inhibitors and small interfering RNA (siRNA). CaMKKbeta is a calcium-activated kinase, and the depletion of intracellular calcium by BAPTA-AM, a Ca(2+) chelator, also curtailed Abeta induced autophagy. Finally, the inhibition of receptor for advanced glycation end products (RAGE) attenuated autophagsome formation and AMPK signaling. Conversely, RAGE overexpression amplified the induction of autophagy. These results implicate the regulation of the Abeta-induced formation of AVs by the RAGE-calcium CaMKKbeta-AMPK pathway and suggest that modulation of autophagosome formation and the interaction between Abeta and RAGE are beneficial in the treatment and prevention of Alzheimer's disease. PMID- 22048126 TI - Dietary salt influences postprandial plasma sodium concentration and systolic blood pressure. AB - The plasma sodium concentration has a direct effect on blood pressure in addition to its effects on extracellular volume regulated through changes in the endothelium. The mechanism for elevated blood pressure seen with habitually increased salt intake is unclear, especially the effect of salt in a single meal on plasma sodium concentration and blood pressure. To resolve this we compared the effect of soup with or without 6 g of salt (an amount similar to that in a single meal) on the plasma sodium concentration and blood pressure in 10 normotensive volunteers using a randomized, crossover design. The plasma sodium concentration was significantly increased by 3.13+/-0.75 mmol/l with salted compared with unsalted soup. Blood pressure increased in volunteers ingesting soup with added salt, and there was a significant positive correlation between plasma sodium concentration and systolic blood pressure. A 1-mmol/l increase in plasma sodium was associated with a 1.91-mm Hg increase in systolic blood pressure by linear regression. Thus, changes in plasma sodium concentration occur each time a meal containing salt is consumed. A potential mechanism for the changes in blood pressure seen with salt intake may be through its effects on plasma sodium concentration. PMID- 22048127 TI - Disruption of Smad4 impairs TGF-beta/Smad3 and Smad7 transcriptional regulation during renal inflammation and fibrosis in vivo and in vitro. AB - The mechanism by which TGF-beta regulates renal inflammation and fibrosis is largely unclear; however, it is well accepted that its biological effects are mediated through Smad2 and Smad3 phosphorylation. Following activation, these Smads form heteromeric complex with Smad4 and translocate into the nucleus to bind and regulate the expression of target genes. Here we studied the roles of Smad4 to regulate TGF-beta signaling in a mouse model of unilateral ureteral obstruction using conditional Smad4 knockout mice and in isolated Smad4 mutant macrophages and fibroblasts. Disruption of Smad4 significantly enhanced renal inflammation as evidenced by a greater CD45(+) leukocyte and F4/80(+) macrophage infiltration and upregulation of IL-1beta, TNF-alpha, MCP-1, and ICAM-1 in the obstructed kidney and in IL-1beta-stimulated macrophages. In contrast, deletion of Smad4 inhibited renal fibrosis and TGF-beta1-induced collagen I expression by fibroblasts. Further studies showed that the loss of Smad4 repressed Smad7 transcription, leading to a loss of functional protein. This, in turn, inhibited IkappaBalpha expression but enhanced NF-kappaB activation, thereby promoting renal inflammation. Interestingly, deletion of Smad4 influenced Smad3-mediated promoter activities and the binding of Smad3 to the COL1A2 promoter, but not Smad3 phosphorylation and nuclear translocation, thereby inhibiting the fibrotic response. Thus, Smad4 may be a key regulator for the diverse roles of TGF-beta1 in inflammation and fibrogenesis by interacting with Smad7 and Smad3 to influence their transcriptional activities in renal inflammation and fibrosis. PMID- 22048128 TI - Indirect measurement of lung density and air volume from electrical impedance tomography (EIT) data. AB - This paper describes a method for estimating lung density, air volume and changes in fluid content from a non-invasive measurement of the electrical resistivity of the lungs. Resistivity in Omega m was found by fitting measured electrical impedance tomography (EIT) data to a finite difference model of the thorax. Lung density was determined by comparing the resistivity of the lungs, measured at a relatively high frequency, with values predicted from a published model of lung structure. Lung air volume can then be calculated if total lung weight is also known. Temporal changes in lung fluid content will produce proportional changes in lung density. The method was implemented on EIT data, collected using eight electrodes placed in a single plane around the thorax, from 46 adult male subjects and 36 adult female subjects. Mean lung densities (+/-SD) of 246 +/- 67 and 239 +/- 64 kg m(-3), respectively, were obtained. In seven adult male subjects estimates of 1.68 +/- 0.30, 3.42 +/- 0.49 and 4.40 +/- 0.53 l in residual volume, functional residual capacity and vital capacity, respectively, were obtained. Sources of error are discussed. It is concluded that absolute differences in lung density of about 30% and changes over time of less than 30% should be detected using the current technology in normal subjects. These changes would result from approximately 300 ml increase in lung fluid. The method proposed could be used for non-invasive monitoring of total lung air and fluid content in normal subjects but needs to be assessed in patients with lung disease. PMID- 22048129 TI - P50 amplitude reduction: a nicotinic receptor-mediated deficit in first-degree relatives of schizophrenia patients. AB - RATIONALE: Impaired P50 gating is a putative index of genetically mediated nicotinic dysfunction in schizophrenia. However, assessment is confounded, in patients, by differential effects of smoking, symptoms, and treatment. OBJECTIVES: This double-blind placebo-controlled study was designed to tease apart the relationships among P50, acute and chronic nicotine exposure, and familial risk. METHODS AND RESULTS: Experiment 1: To assess the putative effects of genetic vulnerability without other confounds, 14 unaffected relatives of schizophrenia patients and 15 controls, all nonsmokers, were tested with/without 7 mg transdermal nicotine. Family members had reduced P50 amplitude to an initial auditory stimulus, but normal P50 gating. Nicotine decreased P50 amplitude in controls; family members had a mixed response: eight decreased and six increased P50 amplitude with nicotine. Experiment 2: To assess chronic nicotine use and short-term withdrawal as a model of nicotinic dysfunction, 26 healthy smokers (14 abstinent for >12 h) received 21 mg transdermal nicotine. Chronic nicotine use, alone, did not alter P50 amplitude or gating. Short-term withdrawal resulted in decreased P50 amplitude, with no effect on P50 gating. Nicotine increased P50 amplitude in abstinent smokers and decreased it in nonabstinent smokers. CONCLUSIONS: Familial vulnerability to schizophrenia reduces P50 amplitude. Nicotinic modulation of this deficit mirrors the effect of nicotine during smoking abstinence and suggests an "inverted-U" relationship between P50 amplitude and endogenous nicotinic activity. P50 amplitude may, therefore, be a sensitive marker of nicotinic dysfunction in individuals with familial risk for schizophrenia, which is mediated through mechanisms (e.g., alpha4beta2 receptors) that are distinct from those (e.g., alpha7 receptors) that mediate P50 gating. PMID- 22048130 TI - Post-retrieval extinction training enhances or hinders the extinction of morphine induced conditioned place preference in rats dependent on the retrieval extinction interval. AB - RATIONALE AND OBJECTIVE: Drug-associated memories are hypothesized to underlie the high risk of relapse in addiction. Recent studies show that post-retrieval extinction training erases fear memories by reconsolidation blockade. Here, we examine the efficacy of this non-invasive procedure in rats with drug-associated memories and explore the underlying mechanisms by varying retrieval-extinction intervals. To confirm the erasure hypothesis, in addition to the conventional spontaneous recovery and reinstatement assays, we conduct further assessment to detect the existence of drug-associated memories. MATERIALS AND METHODS: Morphine induced conditioned place preference (CPP) model in rats was used to examine the effects of post-retrieval extinction training. After the establishment of morphine-induced CPP, CPP testing was used to retrieve drug-associated memories. In the following extinction training session, two groups of rats received conventional extinction training, that is, confined extinction training or repeated testing daily; the other two groups of rats underwent confined extinction training 10 min or 3 h after CPP testing, daily. The recoverability of the extinguished CPP was examined by spontaneous recovery and reinstatement assays. RESULTS: Post-retrieval extinction training with a 10-min retrieval extinction interval facilitated CPP extinction and suppressed the reinstatement and spontaneous recovery of extinguished CPP; nevertheless, CPP returned in the reinstatement assay after the 4-week spontaneous recovery test. In contrast, post retrieval extinction training with a 3-h retrieval-extinction interval retarded the extinction of CPP. CONCLUSION: These results demonstrate that post-retrieval extinction training can either improve or impair CPP extinction depending on the retrieval-extinction interval. PMID- 22048131 TI - Vibratory therapeutics.--The application of rapid and continuous vibrations to the treatment of certain diseases of the nervous system. 1892. PMID- 22048132 TI - Charcot, Freud, and the treatment of "nervous disorders". PMID- 22048133 TI - A contemporary reflection on Charcot and vibratory therapeutics. PMID- 22048134 TI - The prevalence and correlates of sexual risk behaviors and sexually transmitted infections in outpatients with borderline personality disorder. AB - This study examined the prevalence and correlates of sexual risk behaviors and sexually transmitted infections (STIs) in two samples of outpatients with borderline personality disorder (BPD), including suicidal BPD women (n = 99) and opiate-dependent BPD men and women (n = 125). High rates of sexual risk behaviors and STIs were found, particularly in the opiate-dependent BPD sample. Compared with suicidal BPD outpatients, opiate-dependent BPD outpatients reported higher rates of past-year sexual activity, commercial sex work, and lifetime hepatitis, as well as a greater number of lifetime sex partners. Substance use and demographic characteristics (age, sex, and marital status) were associated with higher rates of sexual risk behaviors and/or STIs, whereas cognitive-behavioral factors and indicators of psychiatric impairment were not. These findings point to a clear need for interventions aimed at decreasing sexual risk behaviors among individuals with BPD. PMID- 22048135 TI - Matching the patient to the therapist: the roles of the attachment status and the helping alliance. AB - The helping alliance between patient and therapist is essential in the psychotherapeutic relationship. Recently, the links between patients' attachment and therapeutic alliance were examined. So far, there has been no published study that matched the patients and the patients' attachment representation to examine its role on the therapeutic relationship. Working along Bowlby's assumptions, a dissimilar matching of the attachment status to both was assumed to positively effect the helping alliance. In our study, the attachment representations of 19 psychotherapists and 59 anxiety patients (Structured Clinical Interview for DSM Axis I Disorders) were measured using the Adult Attachment Interview, using the dimensional scales by Waters et al. (Scoring secure versus insecure and dismissing versus preoccupied attachment as continuous variables: Discriminant analysis using AAI state of mind scales; unpublished manuscript). The helping alliance was assessed using the Helping Alliance Questionnaire. As expected, anxiety patients with a more insecure attachment with highly preoccupied and disorganized features evaluated the relationship with a more dismissing therapist as more helpful than that with a more preoccupied therapist. The results indicate the importance of a matching attachment status to a fruitful helping alliance in psychotherapy. PMID- 22048136 TI - Anhedonia is an important factor of health-related quality-of-life deficit in schizophrenia and schizoaffective disorder. AB - The aim of the current study was to investigate an association of physical and social hedonic deficits with health-related quality of life (HRQL), controlling for related distressing and protective factors. Eighty-seven stable patients with schizophrenia (SZ) and schizoaffective disorder (SA) were assessed using the revised Physical Anhedonia Scale (PAS) and the Social Anhedonia Scale (SAS), the Quality of Life Enjoyment and Life Satisfaction Questionnaire (Q-LES-Q), and related factors. Hedonic and HRQL deficit scores did not reach significant differences between SZ and SA patients. General and domain-specific Q-LES-Q scores were significantly correlated with PAS and SAS scores independent of the adverse effects and psychopathological symptoms. Dissatisfaction with HRQL increased from "normal hedonics" (4.8%) to "hypohedonics" (28.6%) and "double anhedonics" (66.7%). Permanently dissatisfied patients who revealed deterioration in general quality of life across 10 years had significantly higher PAS and SAS scores than did patients who were permanently satisfied and improved. An exploratory factor analysis yielded a three-factor solution; PAS and SAS scores were joined to the second factor together with Q-LES-Q, self-efficacy, coping styles, and social support scores. PAS scores accounted for 7% to 13% of the total variance in three domains and in the general quality-of-life alterations. SAS scores did not predict variability in the Q-LES-Q domains. Therefore, physical and social hedonic deficits significantly associated with poor HRQL independent of the adverse effects and psychopathological symptoms of SZ/SA. Physical anhedonia may be a predictor for quality-of-life deficit. PMID- 22048137 TI - Housing status as an independent predictor of functional capacity in patients with schizophrenia. AB - This study compared the functional capacity and neurocognitive status of homeless and housed adults with schizophrenia or schizoaffective disorder and examined whether housing status is an independent predictor of functional capacity. We examined 30 homeless individuals and 21 housed controls and matched for diagnosis, sex, and age. The participants, recruited from an acute psychiatric inpatient unit, completed a measure of psychiatric symptom severity, a neuropsychological test battery, and a measure of functional capacity, the University of California-San Diego performance-based skills assessment (UPSA). There were no significant differences in performance on the neuropsychological test battery or the UPSA between housed and homeless participants. In a multivariate model, however, cognitive status and housing status were independent predictors of functional capacity, and homelessness was associated with an approximately 9-point lower score on the UPSA. This finding highlights the importance of neuropsychological screening and interventions that promote housing stability for patients with schizophrenia. PMID- 22048138 TI - Psychopathological and functional correlates of behavioral activation and avoidance in schizophrenia. AB - Behavioral activation and avoidance are well studied in depression, yet the relationship of these constructs to symptoms, cognitive ability and functioning in schizophrenia is poorly understood. In a sample of 73 middle-aged and older outpatients with schizophrenia (mean [SD] age, 50.3 [6.3] years), we examined the relationship of the Activation and Avoidance subscales of the Behavioral Activation for Depression Scale with measures of psychopathology (positive and negative symptoms, depression), global cognitive ability, and functioning (observer-rated, performance-based, and subjective functioning). Neither activation nor avoidance related to sociodemographic variables, age of onset, or antipsychotic dose. Although activation and avoidance were significantly intercorrelated, only behavioral activation was significantly associated with depression and subjective functioning, whereas only avoidance related to negative symptoms. Avoidance accounted for significant variation in observer-rated functioning after adjusting for cognitive ability. These results suggest that activation and avoidance may be important therapeutic targets in schizophrenia, with somewhat divergent pathways among psychopathological features to functional impairment. PMID- 22048139 TI - Perceptions of and attitudes toward antidepressants: stigma attached to their use -a review. AB - The aim of this study was to ascertain whether there is any evidence of stigma related to the use of antidepressants. Using the PubMed and MEDLINE databases, we searched for the terms stigma, antidepressants, and depression. A protocol was developed to extract information from the papers, which were identified and explored further. Thirty-two papers were identified. We found that the stigma against depression differs from stigma against the use of antidepressants. Stigma against depression does not impact on therapeutic adherence to antidepressant use. Stigma related to antidepressant use appears to be linked with perceived emotional weakness, severity of illness, an inability to deal with problems, and a lack of belief in the therapeutic efficacy of antidepressants. Stigma against medication can be a useful target for interventions, just like the stigma related to depression. However, clinicians must be careful in avoiding the medicalization of symptoms. PMID- 22048140 TI - Use of indigenous cultural idioms by Chinese immigrant relatives for psychosis: impacts on stigma and psychoeducational approaches. AB - Indigenous interpretations of mental illness might negatively impact treatment adherence. However, psychiatric "labeling" potentially leads to stigma among Chinese groups, thus encouraging the use of indigenous idioms. We examined how relatives' use of indigenous labeling varied with the consumers' experience of illness and whether indigenous labeling protected relatives from internalized and experienced forms of stigma. Forty-nine relatives of Chinese-immigrant consumers with psychosis were sampled. Although consumers had progressed to the middle stages of psychosis, 39% of relatives used indigenous idioms to label psychosis. Indigenous labeling decreased when illness duration increased and when visual hallucinations were present. Indigenous labeling further predicted lower internalized stigma among relatives. Relatives who used indigenous labeling also reported fewer indirect stigma experiences, although not after controlling for illness severity. The frequency of direct discrimination among relatives did not differ by labeling. These forms of felt stigma might be embedded into relatives' psychoeducation programs to mitigate adverse consequences of psychiatric labeling. PMID- 22048141 TI - Stigma, help-seeking attitudes, and use of psychotherapy in veterans with diagnoses of posttraumatic stress disorder. AB - Survey and medical record data from 482 Veterans Affairs (VA) patients who recently received diagnoses of posttraumatic stress disorder (PTSD) were examined to determine need and predisposing factors associated with utilization of psychotherapy and counseling. More than half (58%) of participants initiated VA psychotherapy for PTSD within a year of diagnosis. Of those, one third completed eight or more sessions. Roughly two thirds of participants initiated counseling at a Vet Center. Initiating PTSD psychotherapy was associated with greater impairment but not with stigma, concerns about fitting in, or satisfaction with care. The use of Vet Center counseling was associated with desire for help, concerns about fitting in, and satisfaction with care. Unexpectedly, veterans with greater stigma concerns completed more psychotherapy visits and Vet Center counseling. Negative attitudes about mental health treatment did not seem to be substantial barriers to engaging in psychotherapy among these VA patients. Future research should consider enabling treatment system factors in addition to predisposing patient characteristics. PMID- 22048142 TI - Are mobile phones and handheld computers being used to enhance delivery of psychiatric treatment? A systematic review. AB - The rapid diffusion of communication technology has provided opportunities to enhance the delivery of mental health care. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct a qualitative review of randomized controlled trials that reported on the efficacy of mobile phones or handheld computers used to enhance the treatment of psychiatric disorders. We identified eight randomized controlled trials. Five studies used mobile phones to target smoking cessation. Those receiving the smoking cessation intervention were significantly more likely to achieve abstinence compared with those under the control condition. Three studies used non-personal digital assistant (PDA) handheld computers targeting anxiety. Compared with those in the control condition, those who received the non-PDA handheld computer intervention had significant improvement in anxiety outcomes in only one of the three studies. The limited number of rigorous evaluations of mobile phone, PDA, or smartphone interventions for mental health problems underscores the opportunities to enhance our interventions using the available tools of contemporary technology. PMID- 22048143 TI - Addressing demoralization in clinical staff: a true test of leadership. AB - Demoralization is a state that occurs when an individual's personal or professional goals, principles, or values are threatened. Psychiatrists working in mental healthcare organizations may experience demoralization for numerous reasons, including diminished funding for valued programs, personnel reductions, and administrative burdens hindering patient care. Demoralization places psychiatrists and other mental health professionals at increased risk for burnout, and its associated problems related to physical and mental difficulties, poor patient care, and staff losses and turnover. Demoralization, therefore, presents an important challenge to medical and clinical leaders who must address this issue to maintain the organizational commitment to optimal patient-centered care. This can be done using sound and accepted leadership principles coupled with a values orientation. The paper provides an illustration. PMID- 22048144 TI - Assessment of posttraumatic symptoms in patients with first-episode psychosis. AB - Posttraumatic stress disorder is common among patients with psychotic disorders. The present study examined the internal reliability and comparability of the Impact of Event Scale (IES) in a sample of 38 patients with first-episode psychosis and 47 controls exposed to severe physical and/or sexual abuse. The IES total score and both subscales showed high internal consistency in both groups (Cronbach's alpha coefficients of approximately 0.9 or higher). Given their equivalent trauma reporting, the lack of differences in IES scores between patients and controls seems to indicate that patients are likely to report accurately and neither exaggerate nor minimize their posttraumatic symptoms. Overall, the findings suggest that the IES can be used to assess symptoms of posttraumatic stress in patients with psychotic disorders as in other populations. PMID- 22048145 TI - Long-term glucose control among type 2 diabetes patients with and without serious mental illness. AB - Although studies suggest that patients with diabetes with a serious mental illness (SMI) have poor diabetes outcomes, reports conflict regarding the quality of their diabetes care and level of glucose control. In an observational follow up to our initial cross-sectional study, we compared glucose control (glycosylated hemoglobin [HbA1c]) between patients with diabetes with SMI versus those without SMI at two postbaseline assessments during an approximately 5-year period. Both groups continued to have glucose levels higher than what is considered good control and neither group demonstrated a significant change in mean HbA1c at the two follow-up time points. Those with SMI continued to have lower HbA1c levels than those without SMI even after adjusting for potential confounders. More effective strategies are needed to assist patients with diabetes to improve the management of their glucose levels. PMID- 22048146 TI - Joint hypermobility, fears, and chocolate consumption. AB - Our purpose was to evaluate joint hypermobility, an inherited disorder of the connective tissue significantly associated with anxiety disorders, in a sample of nonclinical students in relation to the frequency of severe fears and consumption of chocolate, coffee, cigarettes, and alcohol. One hundred fifty students completed the Hakim and Grahame Simple Questionnaire to detect hypermobility and the self-administered modified Wolpe Fear Scale (100 items). Severe fears and daily consumption of cigarettes, alcohol, coffee, and chocolate were compared with the hypermobility scores. We found significant differences when comparing severe fears between the groups with and without hypermobility (7.6 vs. 11; p = 0.001), reinforcing the hypothesis that the intensity of fears is greater in subjects with hypermobility. Only the frequency of chocolate intake was significantly higher among subjects with hypermobility (31.2% vs. 51.2%; p = 0.038) and may correspond to attempts of self-treatment of the collagen condition. PMID- 22048147 TI - Synthesis of isoindolinones via palladium-catalyzed C-H activation of N methoxybenzamides. AB - The synthesis of isoindolinones from N-methoxybenzamides and alkenes has been achieved by Pd-catalyzed ortho sp(2) C-H activation and intramolecular oxidative amidation, which involve the cleavage of four bonds and formation of two bonds. PMID- 22048148 TI - Investigating changes over time in socioeconomic gaps in cancer survival: using differences in relative survival versus differences in excess mortality rates can give different answers. PMID- 22048149 TI - Validation of a predictive model that identifies patients at high risk of developing febrile neutropaenia following chemotherapy for breast cancer. AB - BACKGROUND: We have previously developed a predictive model that identifies patients at increased risk of febrile neutropaenia (FN) following chemotherapy, based on pretreatment haematological indices. This study was designed to validate our earlier findings in a separate cohort of patients undergoing more myelosuppressive chemotherapy supported by growth factors. PATIENTS AND METHODS: We conducted a retrospective analysis of 263 patients who had been treated with adjuvant docetaxel, adriamycin and cyclophosphamide (TAC) chemotherapy for breast cancer. All patients received prophylactic pegfilgrastim and the majority also received prophylactic antibiotics. RESULTS: Thirty-one patients (12%) developed FN. Using our previous model, patients in the highest risk group (pretreatment absolute neutrophil count<=3.1 10(9)/l and absolute lymphocyte count<=1.5 10(9)/l) comprised 8% of the total population and had a 33% risk of developing FN. Compared with the rest of the cohort, this group had a 3.4-fold increased risk of developing FN (P=0.001) and a 5.2-fold increased risk of cycle 1 FN (P<0.001). CONCLUSIONS: A simple model based on pretreatment differential white blood cell count can be applied to pegfilgrastim-supported patients to identify those who are at higher risk of FN. PMID- 22048150 TI - Attributable causes of cancer in Japan in 2005--systematic assessment to estimate current burden of cancer attributable to known preventable risk factors in Japan. AB - BACKGROUND: To contribute to evidence-based policy decision making for national cancer control, we conducted a systematic assessment to estimate the current burden of cancer attributable to known preventable risk factors in Japan in 2005. METHODS: We first estimated the population attributable fractions (PAFs) of each cancer attributable to known risk factors from relative risks derived primarily from Japanese pooled analyses and large-scale cohort studies and the prevalence of exposure in the period around 1990. Using nationwide vital statistics records and incidence estimates, we then estimated the attributable cancer incidence and mortality in 2005. RESULTS: In 2005, ~ 55% of cancer among men was attributable to preventable risk factors in Japan. The corresponding figure was lower among women, but preventable risk factors still accounted for nearly 30% of cancer. In men, tobacco smoking had the highest PAF (30% for incidence and 35% for mortality, respectively) followed by infectious agents (23% and 23%). In women, in contrast, infectious agents had the highest PAF (18% and 19% for incidence and mortality, respectively) followed by tobacco smoking (6% and 8%). CONCLUSIONS: In Japan, tobacco smoking and infections are major causes of cancer. Further control of these factors will contribute to substantial reductions in cancer incidence and mortality in Japan. PMID- 22048151 TI - Randomized controlled trials in the era of molecular oncology: methodology, biomarkers, and end points. AB - BACKGROUND: We previously reported metrics of systemic therapy randomized controlled trials (RCTs) in breast cancer, colorectal cancer (CRC), and non-small cell lung cancer (NSCLC) published 1975-2004. To evaluate trends in the era of targeted therapies (TT), we have repeated a similar analysis of RCTs published 2005-2009. METHODS: A search for phase III RCTs of systemic agents published in five major journals 2005-2009 was carried out. Trials were classified as TT if they involved any non-hormonal targeted agent. We extracted data regarding biomarker use. Integral biomarkers were defined as tests used to determine eligibility, stratification, or allocation. Descriptive statistics were used to analyze trends over time. RESULTS: One hundred and thirty-seven eligible RCTs were evaluated. Compared with 1995-2004, the number (17-27 RCTs/year) and size (median sample size 446-722, P < 0.001) of RCTs increased. The proportion of RCTs evaluating TT increased from 4% (7/167) to 29% (40/137) (P < 0.001). There was an increase in the proportion of trials with financial support from industry [57% (95/167) to 78% (107/137), P = 0.001]. Biomarkers were included in 58% (80/137) of RCTs; integral biomarkers were included in 36% (49/137) of trials. Among the 49 RCTs using integral biomarkers, 40 (82%) used HER2 and/or ER/PR status in studies of breast cancer. CONCLUSIONS: RCTs published in 2005-2009 are larger, more likely to evaluate TT, and be supported by industry. Biomarkers may be increasingly used, but the most common use relates to traditional use of ER/PR and evolving use of HER2 in breast cancer RCTs. PMID- 22048152 TI - Epidemiology, management and economic impact of febrile neutropenia in oncology patients receiving routine care at a regional UK cancer centre. AB - BACKGROUND: Febrile neutropenia (FN) is a potentially life-threatening complication following chemotherapy. The incidence and mortality of this condition varies according to cancer type and chemotherapy regimen. The aim of the study was to establish the incidence, risk, outcome, infectious cause and economic cost of FN in solid tumour patients within a routine oncology hospital setting. PATIENTS AND METHODS: All FN solid tumour patients admitted to the oncology unit at a UK regional cancer centre were identified over a 12-month period. Demographic data on age, gender, cancer type, disease burden, chemotherapy regimen, antibiotic treatment, length of hospital stay and outcome was obtained. RESULTS: The annual incidence of FN was 19.4 per 1000 oncology admissions. The most common patient groups were those with breast (27%), lung (16%), ovarian (13%) and oesophageal (13%) cancers. The mean length of stay was 9.2 days with an average cost of L2353 for an FN episode per patient. The attributable mortality rate was 12.5%. The majority (83%) of patients who died were >=60 years old, presented with hypotension and had a high-risk FN MASCC index compared with those that survived. CONCLUSIONS: This study demonstrates that FN in solid tumour patients continues to be associated with a significant morbidity and mortality during routine cancer care. Early risk classification of FN may help improve the outcome as well as reduce the economic burden. PMID- 22048153 TI - Endocrine late sequelae in long-term survivors of childhood non-Hodgkin lymphoma. AB - BACKGROUND: Aim of this study was to investigate the long-term endocrine effects of treatment of childhood non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: A single-center cohort of 84 survivors (22 females) was included in this retrospective study. Median age was 21 years (9-40 years) and time after cessation of therapy 12 years (4-30 years). Height, weight, percentage fat, lean body mass (LBM), bone mineral content (BMC), bone mineral density of total body (BMD(TB)) and bone mineral density of lumbar spine (BMD(LS)) were measured. Thyroid-stimulating hormone (TSH), free thyroxin (fT4), insulin-like growth factor-1 (IGF-1), inhibin B and anti-mullerian hormone (AMH) levels were measured. Results were compared with Dutch controls. RESULTS: Height was lower in survivors [mean standard deviation score (SDS) -0.36, P = 0.002], but further analysis showed that shorter stature was already present at diagnosis (mean SDS 0.28, P = 0.023). Body mass index, percentage fat, BMC, BMD(TB) and BMD(LS) were not different from controls. LBM was lower in survivors (mean SDS -0.47, P = 0.008). TSH, fT4 and IGF-1 were normal in all survivors. Three of 20 adult females had low AMH levels and 23 of 42 adult males had low inhibin B levels. CONCLUSIONS: Twelve years after cessation of treatment, NHL survivors did not develop adiposity, osteoporosis or thyroid disease. Male survivors may be at risk for infertility. PMID- 22048154 TI - Heterogeneity among lists of cautioned or prohibited drugs in protocols of early phase oncology trials. AB - BACKGROUND: To prevent potential drug-drug interaction, lists of cautioned or prohibited (C/P) drugs are commonly included in protocols of phases I and II cancer trials. Heterogeneity among lists may affect patient eligibility and comparability of results. METHODS: Protocols of phase I/II trials conducted at an academic cancer centre between 2004 and 2009 were reviewed. All C/P drugs were collected and compared among trials. RESULTS: Of 100 protocols reviewed, 77 protocols include lists of C/P drugs to prevent CYP3A4-, 2C9- and 2C19-related interactions and/or QT interval prolongation. Sixty-five protocols evaluating 38 unique study drugs include lists of CYP3A4-related C/P drugs. These lists contain 0-137 inhibitors [coefficient of variation (CV): 123%], 0-20 inducers (CV: 57%) and 10-157 substrates (CV: 76%). There is a high degree of inconsistency among protocols of the same study drug or from the same originator. Heterogeneity is also common for lists of C/P CYP2C9 and 2C19 drugs and for QT interval prolongation drugs. Approximately 20% protocols contain potential sources of confusion in their drug lists. CONCLUSIONS: There is high degree of heterogeneity among lists of drugs C/P in protocols of oncology phase I/II trials. There is an urgent need to standardize these lists. PMID- 22048156 TI - High output nanogenerator based on assembly of GaN nanowires. AB - GaN nanowires (NWs) were synthesized through a vapor-liquid-solid (VLS) process. Based on structural analysis, the c-axis of the NW was confirmed to be perpendicular to the growth direction. Nanogenerators (NGs) fabricated by rational assembly of the GaN NWs produced an output voltage up to 1.2 V and output current density of 0.16 uA cm-2. The measured performance of the GaN NGs was consistent with the calculations using finite element analysis (FEA). PMID- 22048155 TI - Kidins220/ARMS mediates the integration of the neurotrophin and VEGF pathways in the vascular and nervous systems. AB - Signaling downstream of receptor tyrosine kinases controls cell differentiation and survival. How signals from different receptors are integrated is, however, still poorly understood. In this work, we have identified Kidins220 (Kinase D interacting substrate of 220 kDa)/ARMS (Ankyrin repeat-rich membrane spanning) as a main player in the modulation of neurotrophin and vascular endothelial growth factor (VEGF) signaling in vivo, and a primary determinant for neuronal and cardiovascular development. Kidins220(-/-) embryos die at late stages of gestation, and show extensive cell death in the central and peripheral nervous systems. Primary neurons from Kidins220(-/-) mice exhibit reduced responsiveness to brain-derived neurotrophic factor, in terms of activation of mitogen-activated protein kinase signaling, neurite outgrowth and potentiation of excitatory postsynaptic currents. In addition, mice lacking Kidins220 display striking cardiovascular abnormalities, possibly due to impaired VEGF signaling. In support of this hypothesis, we demonstrate that Kidins220 constitutively interacts with VEGFR2. These findings, together with the data presented in the accompanying paper, indicate that Kidins220 mediates the integration of several growth factor receptor pathways during development, and mediates the activation of distinct downstream cascades according to the location and timing of stimulation. PMID- 22048157 TI - Stable fluorescent gold nanoparticles for detection of Cu2+ with good sensitivity and selectivity. AB - A simple and one-pot method for the synthesis of water-soluble, red-emitting, highly fluorescent gold nanoparticles has been reported using 11 mercaptoundecanoic acid (11-MUA) as the protecting group. We found that the fluorescent gold nanoparticles could selectively detect copper ions in aqueous solution, with a limit of detection of about 87 nM. PMID- 22048158 TI - On-chip sample preparation by controlled release of antibodies for simple CD4 counting. AB - We present a simple system for CD4 and CD8 counting for point-of-care HIV staging in low-resource settings. Automatic sample preparation is achieved through a dried reagent coating inside a thin (26 MUm) counting chamber, allowing the delayed release of fluorochrome conjugated monoclonal antibodies after the filling of the chamber with whole blood by capillary flow. A custom-built image cytometer is used to capture fluorescence images representing more than 1 MUl of blood. The thin layer of blood in combination with the large image area allows the use of whole blood from a finger prick without the need for dilution, lysis or cell enrichment. Automatic cell counting of CD4(+) and CD8(+) T-lymphocytes correlates well with results obtained by flow cytometry. PMID- 22048159 TI - Pearls and pitfalls of magnetic resonance imaging of the upper extremity. AB - Magnetic resonance imaging (MRI) is capable of producing images in any anatomical plane, visualizing and analyzing a variety of tissue characteristics, as well as quantifying blood flow and metabolic functions. Although MRI details of compact bone and calcium are poor when compared to those taken with plain radiography or computed tomography, its high soft tissue contrast discrimination and multiplanar imaging capabilities are significant advantages. Musculoskeletal anatomy and neurovascular bundles are well delineated. The advent of MRI has revolutionized the clinician's ability to confirm a proper diagnosis for musculoskeletal problems, which has led to more directed, specific rehabilitative protocols. However, the value of MRI to rehabilitative professionals has been even greater in its ability to identify serious, more uncommon pathologies, such as in those with underlying infection, fracture, or tumor, that require immediate care and are considered to be beyond their scope of practice. Furthermore, MRI, with its precise delineation of fat, muscle, and bone, is an ideal candidate for imaging of muscle disease or injury and has emerged as the method of choice for the detection of early cartilage wear in young patients, such as osteoarthritis. Finally, this imaging modality can avoid radiation exposure in a predominantly younger patient cohort commonly affected by musculoskeletal diseases. The aim of this paper is to consider how physical therapists may take advantage of the diagnostic value of MRI of the upper limb, while avoiding the pitfalls of misinterpretation of images as a result of technical issues, pathological changes, or normal variants. PMID- 22048160 TI - Aminoguanidine down-regulates the expression of mreB-like protein in Bacillus subtilis. AB - Nitric oxide synthase (NOS), the enzyme responsible for the production of endogenous nitric oxide from arginine, has been recently discovered in a number of Gram-positive bacteria. While bacterial NOS has been implicated in mediating nitrosative stress, much remains unknown about the functional role of endogenous nitric oxide in bacteria. Using the known NOS inhibitor aminoguanidine, we examined changes in the protein expression profile using two-dimensional gel electrophoresis. Treatment with aminoguanidine induced several changes in protein expression in Bacillus subtilis. In particular, mreB-like protein (Mbl) was fully down-regulated in the aminoguanidine-treated samples. The expression of Mbl was also examined by reverse transcriptase-polymerase chain reaction and Mbl was found to be fully down-regulated at the transcriptional level as well. Given the role that Mbl plays in the maintenance of cytoskeletal structure, it appears that bacterial NOS may participate in specific biosynthetic pathways with ramifications toward the regulation of antibiotic resistance. PMID- 22048161 TI - Cystic and non-cystic fibrosis Pseudomonas aeruginosa isolates are not differentiated by the quorum-sensing signaling and biofilm production. AB - The capability for biofilm and quorum-sensing (QS) signaling production among Pseudomonas aeruginosa isolates were evaluated. A total of 231 isolates were recovered from sputa of cystic fibrosis (CF, n = 104) and non-CF (non-CF, n = 127) patients. One hundred ninety-seven (85.3%; 95% CI 80.1-89.3%) were biofilm producers and 157 (68%; 95% CI 61.7-73.6%) were weak QS-producing. No difference was observed between CF and non-CF isolates regarding the ability to produce biofilm and QS-signaling. Interestingly, the degree of QS production appears to be related to the degree of biofilm production. Thus, blocking QS pathways may be crucial in the prevention and treatment of biofilm-related infections. PMID- 22048162 TI - Green chemistry oriented organic synthesis in water. AB - The use of water as solvent features many benefits such as improving reactivities and selectivities, simplifying the workup procedures, enabling the recycling of the catalyst and allowing mild reaction conditions and protecting-group free synthesis in addition to being benign itself. In addition, exploring organic chemistry in water can lead to uncommon reactivities and selectivities complementing the organic chemists' synthetic toolbox in organic solvents. Studying chemistry in water also allows insight to be gained into Nature's way of chemical synthesis. However, using water as solvent is not always green. This tutorial review briefly discusses organic synthesis in water with a Green Chemistry perspective. PMID- 22048163 TI - Assembly of the transcription machinery: ordered and stable, random and dynamic, or both? AB - The assembly of the transcription machinery is a key step in gene activation, but even basic details of this process remain unclear. Here we discuss the apparent discrepancy between the classic sequential assembly model based mostly on biochemistry and an emerging dynamic assembly model based mostly on fluorescence microscopy. The former model favors a stable transcription complex with subunits that cooperatively assemble in order, whereas the latter model favors an unstable complex with subunits that may assemble more randomly. To confront this apparent discrepancy, we review the merits and drawbacks of the different experimental approaches and list potential biasing factors that could be responsible for the different interpretations of assembly. We then discuss how these biases might be overcome in the future with improved experiments or new techniques. Finally, we discuss how kinetic models for assembly may help resolve the ordered and stable vs. random and dynamic assembly debate. PMID- 22048165 TI - A multichromophoric dendrimer: from synthesis to energy up-conversion in a rigid matrix. AB - A dendrimer with a [Ru(bpy)(3)](2+) (bpy = 2,2'-bipyridine) complex as a core and four diphenylanthracene units at the periphery was prepared from a scaffold based on a bipyridyl ligand bearing four terminal alkyne groups. Upon green light excitation, the dendrimer shows blue luminescence even in a rigid matrix at 77 K thanks to the dendritic multichromophoric structure. PMID- 22048164 TI - DNA glycosylases: in DNA repair and beyond. AB - The base excision repair machinery protects DNA in cells from the damaging effects of oxidation, alkylation, and deamination; it is specialized to fix single-base damage in the form of small chemical modifications. Base modifications can be mutagenic and/or cytotoxic, depending on how they interfere with the template function of the DNA during replication and transcription. DNA glycosylases play a key role in the elimination of such DNA lesions; they recognize and excise damaged bases, thereby initiating a repair process that restores the regular DNA structure with high accuracy. All glycosylases share a common mode of action for damage recognition; they flip bases out of the DNA helix into a selective active site pocket, the architecture of which permits a sensitive detection of even minor base irregularities. Within the past few years, it has become clear that nature has exploited this ability to read the chemical structure of DNA bases for purposes other than canonical DNA repair. DNA glycosylases have been brought into context with molecular processes relating to innate and adaptive immunity as well as to the control of DNA methylation and epigenetic stability. Here, we summarize the key structural and mechanistic features of DNA glycosylases with a special focus on the mammalian enzymes, and then review the evidence for the newly emerging biological functions beyond the protection of genome integrity. PMID- 22048166 TI - TRAIL promotes caspase-dependent pro-inflammatory responses via PKCdelta activation by vascular smooth muscle cells. AB - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is best known for its selective cytotoxicity against transformed tumor cells. Most non transformed primary cells and several cancer cell lines are not only resistant to death receptor-induced apoptosis, but also subject to inflammatory responses in a nuclear factor-kappaB (NF-kappaB)-dependent manner. Although the involvement of TRAIL in a variety of vascular disorders has been proposed, the exact molecular mechanisms are unclear. Here, we aimed to delineate the role of TRAIL in inflammatory vascular response. We also sought possible molecular mechanisms to identify potential targets for the prevention and treatment of post-angioplastic restenosis and atherosclerosis. Treatment with TRAIL increased the expression of intercellular adhesion molecule-1 by primary human vascular smooth muscle cells via protein kinase C (PKC)delta and NF-kappaB activation. Following detailed analysis using various PKCdelta mutants, we determined that PKCdelta activation was mediated by caspase-dependent proteolysis. The protective role of PKCdelta was further confirmed in post-traumatic vascular remodeling in vivo. We propose that the TRAIL/TRAIL receptor system has a critical role in the pathogenesis of inflammatory vascular disorders by transducing pro-inflammatory signals via caspase-mediated PKCdelta cleavage and subsequent NF-kappaB activation. PMID- 22048167 TI - Temporal blastemal cell gene expression analysis in the kidney reveals new Wnt and related signaling pathway genes to be essential for Wilms' tumor onset. AB - Wilms' tumors (WTs) originate from metanephric blastema cells that are unable to complete differentiation, resulting in triphasic tumors composed of epithelial, stromal and blastemal cells, with the latter harboring molecular characteristics similar to those of the earliest kidney development stages. Precise regulation of Wnt and related signaling pathways has been shown to be crucial for correct kidney differentiation. In this study, the gene expression profile of Wnt and related pathways was assessed in laser-microdissected blastemal cells in WTs and differentiated kidneys, in human and in four temporal kidney differentiation stages (i.e. E15.5, E17.5, P1.5 and P7.5) in mice, using an orthologous cDNA microarray platform. A signaling pathway-based gene signature was shared between cells of WT and of earliest kidney differentiation stages, revealing genes involved in the interruption of blastemal cell differentiation in WT. Reverse transcription-quantitative PCR showed high robustness of the microarray data demonstrating 75 and 56% agreement in the initial and independent sample sets, respectively. The protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was characterized in WTs and in a panel of human fetal kidneys displaying remarkable aspects of differentiation, which was recapitulated in the tumor. Taken together, this study reveals new genes candidate for triggering WT onset and for therapeutic treatment targets. PMID- 22048168 TI - WIN55,212-2 induces cytoplasmic vacuolation in apoptosis-resistant MCL cells. AB - Cannabinoid receptors 1 (CB1) and/or 2 (CB2) are overexpressed in many types of human malignancies including mantle cell lymphoma (MCL). Agonists to CB1 and CB2 promote ceramide de novo synthesis, p38-mitogen-activated protein kinase dependent activation of caspase-3 and apoptotic cell death in most MCLs. However, in this report we describe that in some MCLs the response to treatment with cannabinoids decreased cell viability as assessed by metabolic activity but did not involve the caspase-3 cascade or loss of plasma membrane integrity. Both primary cells from one MCL patient and the MCL cell line Granta519 responded to treatment with cannabinoids by formation of cycloheximide-sensitive cytoplasmic vacuoles, but did not enter apoptosis. The persistent expression of mammalian homolog of Atg8 with microtubule-associated protein-1 light chain-3 II (LC3 II) and p62, as well as the lack of protection from chloroquine, indicates that lysosomal degradation is not involved in this cytoplasmic vacuolation process, distinguishing from classical autophagy. Transmission electron microscopy images and immunofluorescence staining of endoplasmic reticulum (ER) chaperone calreticulin showed that the vacuoles were of ER origin and that chromatin remained normal. These features resemble paraptosis-like cell death-a third type of a programmed cell death not previously described in response to cannabinoids. PMID- 22048169 TI - Kidins220/ARMS is an essential modulator of cardiovascular and nervous system development. AB - The growth factor family of neurotrophins has major roles both inside and outside the nervous system. Here, we report a detailed histological analysis of key phenotypes generated by the ablation of the Kinase D interacting substrate of 220 kDa/Ankyrin repeat-rich membrane spanning (Kidins220/ARMS) protein, a membrane anchored scaffold for the neurotrophin receptors Trk and p75(NTR). Kidins220 is important for heart development, as shown by the severe defects in the outflow tract and ventricle wall formation displayed by the Kidins220 mutant mice. Kidins220 is also important for peripheral nervous system development, as the loss of Kidins220 in vivo caused extensive apoptosis of DRGs and other sensory ganglia. Moreover, the neuronal-specific deletion of this protein leads to early postnatal death, showing that Kidins220 also has a critical function in the postnatal brain. PMID- 22048170 TI - Novel semisquaraine regioisomers: isolation, divergent chemical reactivity and photophysical properties. AB - A zwitterionic semisquaraine 1,3-regioisomer which exhibits distinct photophysical properties and chemical reactivity was isolated. Uniquely, this isomer has been identified as the reactive intermediate in the squaraine dye formation reaction rather than the neutral 1,2-isomer and opens up new avenues for the synthesis of novel dyes for optoelectronic applications. PMID- 22048171 TI - Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study. AB - The immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(r), GlaxoSmithKline Biologicals) administered according to its licensed vaccination schedule (3-dose, 3D) and formulation (20 MUg of each HPV antigen; 20/20F) has previously been demonstrated. This partially-blind, controlled, randomized trial (NCT00541970) evaluated 2-dose (2D) schedules using the licensed 20/20F or an alternative formulation containing 40 MUg of each antigen (40/40F), compared with the licensed 3D schedule. Healthy females stratified by age (9-14, 15-19, 20-25 y) were randomized to receive 2 doses of 20/20F at Months (M) 0,6 (n=240), 40/40F at M0,6 (n=241) or 40/40F at M0,2 (n=240), or 3 doses of 20/20F at M0,1,6 (licensed schedule/formulation, n=239). One month after the last dose, the 3D schedule was not immunologically superior to 2D schedules except in the 40/40F M0,2 group for HPV-16 (lower limit of 95% CI geometric mean antibody titer (GMT) ratio [2D/3D] < 0.5). For both HPV-16 and HPV 18, the 2D schedules in girls 9-14 y were immunologically non-inferior to the 3D schedule in women 15-25 y (the age group in which efficacy has been demonstrated) (upper limit of 95% CI for GMT ratio [3D/2D] < 2) one month after the last dose. At Month 24, non-inferiority was maintained for the 2D M0,6 schedules in girls 9 14 y versus the 3D schedule in women 15-25 y. All formulations had acceptable reactogenicity and safety profiles. These results indicate that the HPV-16/18 vaccine on a 2D M0,6 schedule is immunogenic and generally well tolerated in girls 9-14 y and that the 2D schedule is likely adequate for younger females. PMID- 22048174 TI - Self-assembly of an antireflective moth-like structure using antibody functionalized nanowires and nanopore arrays. AB - A novel framework to fabricate moth-like nanopillar arrays was proposed. In this scheme, nanowires were first cross-linked with anti-gold nanoparticle (GNP) antibodies and mixed with the nanopore array pre-deposited by GNP, which was then followed by centrifugation. An optimal success rate of 95% was finally obtained by choosing nanorods with an aspect ratio of 5:1 by modifying with 10 ng mL-1 antibodies, and by inserting them into a pore array pre-deposited with 54.4 uM GNP. The nanopillar arrays thus fabricated showed high levels of antireflective efficiency across a broad wavelength. Here we demonstrate the assembly of nanowires and nanopores into nanopillar arrays by the assistance of antibody antigen binding. The application of bio-nano-interaction provides an economic, time-saving, and throughput approach to manipulating objects on the nanoscale. PMID- 22048172 TI - Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18-45 years. AB - Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines (HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck & Co., Inc.) differ in terms of protection against oncogenic non-vaccine HPV types 31/45. The immune responses induced by the two vaccines against these two non vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo post-vaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed (HPV-010 [NCT00423046]). Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0-16.7%) versus the HPV-6/11/16/18 vaccine (0.0-5.0%) for HPV-45 with PBNA, but not ELISA. HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (HPV-31 [geometric mean ratio [GMR] =2.0; p=0.0002] and HPV-45 [GMR=2.6; p=0.0092]), as were the proportion of T-cell responders (HPV-31, p=0.0009; HPV-45, p=0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection. PMID- 22048173 TI - Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12-24 in a Phase III randomized study of healthy women aged 18-45 years. AB - In this observer-blind study (NCT00423046), women (N=1,106), stratified by age (18-26, 27-35, 36-45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix(r), GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil(r) Merck & Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5-100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0-100% (HPV-16/18 vaccine) and 72.3-84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4-5.8-fold higher for HPV-16 and 7.7-9.4-fold higher for HPV-18 with the HPV-16/18 vaccine versus the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p< 0.0001) in the total vaccinated cohort (received >=1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4+ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection. PMID- 22048175 TI - Immunizations in children with chronic kidney disease. AB - Children with chronic kidney disease (CKD) are at increased risk for vaccine preventable diseases. These patients may have a reduced response to and/or reduced duration of antibody after immunization and therefore monitoring of antibody levels or titers is indicated for some vaccines. In addition, pediatric CKD patients require immunizations not routinely provided to healthy children. Unfortunately, studies in pediatric CKD patients, including those on dialysis and awaiting kidney transplantation, have demonstrated sub-optimal immunization rates. In order to minimize the risk for vaccine-preventable disease in pediatric CKD patients, it is imperative that all who care for these patients remain abreast of the recommended childhood immunization schedule, as well as alterations to this schedule required for children with CKD, including end-stage kidney disease. This article reviews recent changes to the recommended childhood immunization schedule and alterations and additions to this schedule recommended for children with CKD. Where available, data on antibody response to immunizations in children with CKD are presented. PMID- 22048176 TI - Converting steady laminar flow to oscillatory flow through a hydroelasticity approach at microscales. AB - We report a hydroelasticity-based microfluidic oscillator that converts otherwise steady laminar flow to oscillatory flow. It incorporates an elastic diaphragm to enhance nonlinearity of the flow. Negative differential flow resistance is observed. High-frequency oscillatory flow is produced passively through interactions among hydrodynamic, elastic and inertial forces, without resorting to external actuators and control equipment. Driven by fluid flow and pressure, this device can operate in either steady laminar flow or oscillatory flow states, or work as a valve. Its applications for flow control and operation, and mixing enhancement are demonstrated. PMID- 22048177 TI - Osteonecrosis of the distal tibia metaphysis after a Salter-Harris I injury: a case report. AB - Posttraumatic osteonecrosis has been well described as a common phenomenon seen in fractures of the femoral neck, talus, and scaphoid. In the following case, we describe posttraumatic osteonecrosis in a rare location: the distal tibia. Our report details a child who sustained a distal tibia physeal injury and subsequently developed radiographic findings consistent with aseptic necrosis. Besides a traumatic incident, the patient did not have any of the risk factors known to cause osteonecrosis. Awareness of this complication after Salter-Harris I fractures will help reduce time to diagnosis and optimize treatment. PMID- 22048178 TI - Reimplantation of an extruded osteoarticular segment of the distal tibia in a 14 year-old girl. Case report and review of the literature. AB - This case report describes the reimplantation of a 15-cm osteoarticular segment of the distal tibia in a 14-year-old girl who was hit by a truck. The bone fragment was debrided and reimplanted on the day of injury. A free flap was performed within 1 week. Bony union was achieved without complication. At 5-year follow-up, the patient is able to ambulate for several hours at a time without an assistive device, although arthritis of the ankle joint is present. She scores 43.8 on the physical component of the 36-Item Short Form Health Survey and 49.0 on the mental component. The patient states that she is very pleased with her outcome. This seems to be the first description of an osteoarticular segment reimplantation of a long bone in the orthopaedic literature. PMID- 22048179 TI - Oblique distraction external pelvic fixation. AB - Simple anterior pelvic external fixation is a safe and effective strategy for reduction of pelvic ring deformity as well as the provisional or definitive stabilization of selected patterns of pelvic ring disruption. A two-pin oblique anterior pelvic deformity correction frame is a unique frame configuration designed to reduce and stabilize lateral compression pelvic ring disruptions associated with flexion/internal rotation hemipelvic deformities. In a small case series, we demonstrate that the oblique distraction external fixation frame alone or in combination with internal fixation is a simple and safe strategy for reduction and stabilization of unstable multiplanar hemipelvic deformities associated with partial posterior ring stability. PMID- 22048180 TI - The surgical treatment of isolated mason type 2 fractures of the radial head in adults: comparison between radial head resection and open reduction and internal fixation. AB - OBJECTIVES: To compare the outcomes of two different surgical treatments for the management of isolated closed Mason Type 2 radial head fractures. DESIGN: Retrospective study. The Student t test and McPearson chi-square test were used to evaluate whether there was a significance difference between the groups. PATIENTS: Fifty-nine patients with isolated Mason Type 2 radial head fractures. INTERVENTION: Twenty-four patients treated with radial head excision (Group I) and 35 treated with open reduction and internal fixation (Group II). MAIN OUTCOME MEASUREMENTS: Clinical outcomes were assessed using the Broberg and Morrey functional rating scores and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire. Orthogonal radiographs were performed on both the elbow and the wrist; these were assessed for the presence of arthritis, heterotopic ossification, and the degree of proximal radial migration. RESULTS: The length of postoperative follow-up was 157 +/- 61.84 months (Group I) and 125 +/- 39.09 months (Group II). The Broberg and Morrey functional rating score was 86.21 +/- 6.10 points and 95.09 +/- 4.78 points, respectively. The DASH score was 21.82 +/- 6.01 points and 2.81 +/- 2.73 points, respectively. Radiologically moderate or severe osteoarthritis was present in the elbows of nine patients in Group I and only two patients in Group II. CONCLUSIONS: Patients with isolated Mason Type 2 radial head fractures treated by open reduction and internal fixation (Group II) had less residual pain, greater range of motion, and better strength than patients treated by radial head excision (Group I). Additionally, Group II had a lower incidence of severe posttraumatic arthritis, which contributed to improved DASH and Broberg and Morrey functional scores. These results support open reduction and internal fixation as the treatment of choice for these fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 22048181 TI - A simple technique for removing a locking compression plate with a stripped locking screw. AB - We use a straightforward technique to remove a locking compression plate and a screw with a stripped hexagonal recess. If the hexagonal recess of the screw had been stripped during attempts at screw removal using a conical extraction device, we perform the following procedure after loosening the contact surface between the bone and the plate. Using a larger drill bit, another hole is drilled immediately adjacent to the screw through the nonlocking portion of the combination hole. The plate is struck along the line connecting the screw to the newly formed hole. Using an elevator, leverage force is then applied to the plate, which can be removed with the stripped screw attached. This technique can be used to remove plates with several stripped screws and does not require any special tools. PMID- 22048182 TI - Pregnancy outcomes after pelvic ring injury. AB - OBJECTIVES: Previous studies reported negative effects of pelvic trauma on genitourinary and reproductive function with frequent cesarean delivery. Risk factors for cesarean delivery have not been well defined. The purpose of this project was to evaluate outcomes of pregnancy after pelvic ring injury. We hypothesized that cesarean delivery would be more frequent after pelvic fracture with potential causes including patient and physician preference, malunion, and retained hardware. DESIGN: Retrospective review with prospective collection of obstetric information. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Thirty-one women, 16 to 40 years old, with pregnancy after healed pelvic fracture. INTERVENTION: Orthopaedic Trauma Association (OTA) classification included 10 B-type and 21 C-type fractures, 17 (55%) of which were treated surgically. MAIN OUTCOME MEASUREMENTS: Obstetric questionnaires were obtained for 54 pregnancies after a mean 72 months follow-up. RESULTS: Sixteen women had 25 vaginal deliveries; 28% after surgical treatment for their pelvic fracture with retained anterior (16%) and/or posterior (16%) hardware, including transsymphyseal plating in three patients (12%). Thirteen women had 26 cesarean deliveries, 46% after surgical treatment for their pelvis. The new cesarean delivery rate was 44% versus 17% preinjury (P = 0.02). Two had cesarean deliveries as repeat procedures after preinjury cesarean delivery. Four had cesarean deliveries as a result of medical complications (pre-eclampsia, n = 2; breech, n = 1; labor arrest, n = 2). Seven women (54%) reported 12 cesarean deliveries (46%) resulting from pelvic fracture; three elected cesarean delivery despite their physician offering a trial of labor, whereas four were advised by their obstetrician. Cesarean delivery was not related to age, fracture pattern, treatment type, or residual pelvic displacement. A trend for cesarean delivery related to retained hardware was observed (P = 0.06). CONCLUSIONS: Uncomplicated pregnancies and deliveries are possible after pelvic fracture. The new cesarean delivery rate among these women is significantly increased with over half related to patient and obstetrical preferences. Fracture pattern, minor malalignment, and retained hardware are not absolute indications for cesarean delivery. Neither surgical care of the pelvis or retained fixation precludes successful vaginal delivery. Development of guidelines and objective indications for trial of normal labor after pelvic fracture is needed. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 22048183 TI - Treatment of unstable pelvic ring injuries with an internal anterior fixator and posterior fixation: initial clinical series. AB - OBJECTIVES: To present a novel internal fixation device for stabilizing unstable pelvic fractures using supra-acetabular spinal pedicle screws and a subcutaneous connecting rod (INFIX). SETTING: Level I trauma center. DESIGN: Case series. PATIENTS: Twenty-four patients with rotational or vertically unstable pelvic fractures that reported to a level I trauma center. METHODS/INTERVENTION: Surgical treatment of unstable pelvic fractures included reduction, appropriate posterior fixation where indicated, and an anterior subcutaneous internal fixator. MAIN OUTCOME MEASUREMENT: Healing time, quality and loss of reduction, ease of nursing, incidence of complications, including nonunion, infection, and patient mobility and comfort. RESULTS: In the present clinical series, all fractures healed without significant loss of reduction. There were no infections, delayed unions or nonunions. Nursing care was observed to be easier especially in the intensive care unit setting. Complications included unilateral anterior thigh paresthesias in 2 patients, and 1 patient each required repositioning of the pedicle screw and readjustment of screw rod junction. Patients tolerated the procedure well and were fairly mobile after the procedure. CONCLUSIONS: The reported technique allows for a definitive and stable anterior fixation of vertically and rotationally unstable pelvic fractures when combined with the appropriate posterior fixation if indicated. The potential complications are acceptable with this technique and good outcomes were achieved. A second operative procedure is required for removal of the device. It is our view that its best indication is in obese individuals, in whom other options have shortcomings. PMID- 22048184 TI - Infraglenoid tubercle avulsion and greater tuberosity fracture resulting from traumatic glenohumeral anterior dislocation: a case report. AB - Traumatic anterior shoulder dislocation can be associated with anteroinferior glenoid bone loss causing potential recurrent instability. We report on a 62-year old man with a first-time traumatic anterior dislocation of the right shoulder, resulting in both an infraglenoid tubercle triceps avulsion fracture and a greater tuberosity fracture. After reduction, nonsurgical management was chosen. No inferior-oriented apprehension was noticed during follow-up, which might necessitate surgical treatment of the inferior glenoid rim. At latest follow-up, the patient had recovered his shoulder function. Avulsion fractures of the infraglenoid tubercle are uncommon lesions after an anterior shoulder dislocation and, without signs of instability, can be treated conservatively. PMID- 22048185 TI - Successful knee extensor mechanism reconstruction in a warfare-related open lower extremity injury complicated by mucormycosis infection: a case report. AB - Subcutaneous zygomycosis infection associated with a lower extremity open fracture is a potentially life- and limb-threatening condition. This rare and poorly characterized infection complicating war wounds is unique, complex, and poses a significant reconstructive challenge. The objective of this article is to report the reconstruction of a complex Gustilo IIIC warfare-related distal femur fracture with partial extensor mechanism loss complicated by a subcutaneous zygomycosis infection using a novel combination of local and systemic antifungals with negative pressure wound therapy. Negative pressure wound therapy with silver impregnated sponges and antibiotic/antifungal beads was used to provide temporary wound coverage, improve revascularization, and deliver local antifungal therapy. The distal open femur fracture was fixed using a lateral approach and the medial distal thigh wound and extensor mechanism were reconstructed using an extended gastrocnemius flap with skin graft. The limb was successfully salvaged and the patient is now ambulatory. PMID- 22048186 TI - Chronic posterior sternoclavicular dislocation. AB - SUMMARY: Posterior sternoclavicular dislocation is a rare injury that involves a risk of concomitant injuries to mediastinal structures. We report a 23-year-old man who underwent open reduction and fixation with a plantaris tendon graft after 13 weeks. The clinical and radiologic outcome was good. PMID- 22048187 TI - The lateral decubitus approach for complex proximal femur fractures: anatomic reduction and locking plate neutralization: a technical trick. AB - SUMMARY: Unstable intertrochanteric or subtrochanteric fractures with significant proximal or distal extension or comminution are often a challenge for achieving stable fixation. In recent years, locked proximal femoral plates have been developed that aid fixation of these complex fractures often permitting the biological advantages of minimal contact or minimally invasive application. Although previously described with success using a standard lateral approach in the supine position, we describe a lateral decubitus position for the locked plating of proximal femur fractures. We have found that lateral positioning neutralizes the gravitational forces acting on the bone and soft tissues, facilitating reduction and exposure while continuing to be compatible with intraoperative image intensification. We present lateral positioning as a technical trick for anatomic and stable reduction of complex proximal femur fractures with proximal femoral locking plates and present a series of 10 cases that were treated with this combination of approach and internal fixation. PMID- 22048188 TI - Preventing instability of the Taylor Spatial Frame (TSF) during a strut change. AB - SUMMARY: During treatment with a Taylor Spatial Frame, some of the struts may need to be exchanged for one of a different length. An extra "seventh" strut is usually added to the frame during this procedure. This article describes a "technical trick" to ensure stability during a strut change. The frame was stable whenever the orientation of the "acute ring-strut" of the temporary strut matched that of the strut being exchanged. Clinicians must anticipate that instability can exist during strut changes, and this will depend on the particular configuration and position of the frame. Applying the rule indentified in this article may prevent instability, pain, and tissue damage. PMID- 22048189 TI - Anterior pelvic reduction and fixation using a subcutaneous internal fixator. AB - Acute traumatic pelvic instability mandates reduction and mechanical stabilization to maximize the chance of a good functional outcome. Posterior pelvic fixation is frequently inadequate to stabilize the pelvic ring in isolation. Fixation augmentation with anterior pelvic ring implants can take several forms, including plates, medullary screws, or external fixation. Based on a multitude of patient and injury factors, external fixation may be the definitive anterior pelvic implant of choice. However, many drawbacks exist with this treatment, most notably the high infection rates of the transcutaneous pins, impaired patient mobilization, and suboptimal mechanical properties. We present a technique of a subcutaneous anterior pelvic fixator as an alternative method of anterior pelvic ring reduction and stabilization that avoids many of the drawbacks of traditional anterior pelvic external fixation. PMID- 22048190 TI - K. Masumori, K. Maeda, Y. Koide, T. Hanai, H. Sato, H. Matsuoka, H. Katsuno, T. Noro, K. Honda, T. Endo, S. Shiota and S. Matsuoka: simple excision and closure of a distal limb of loop colostomy prolapse by stapler device. PMID- 22048191 TI - Pelvic exenteration for recurrent colonic malignancy. PMID- 22048192 TI - The pearls and pitfalls of magnetic resonance imaging of the lower extremity. AB - This article is intended for the clinician charged with either diagnosing or treating patients with lower extremity symptoms thought to be of musculoskeletal etiology. It gives a brief overview of the imaging techniques that can be utilized, common pathology, and certain pearls and pitfalls that may be encountered in both ordering and interpreting lower extremity magnetic resonance imaging. While we cannot present a comprehensive discussion of all of the known disorders in the lower extremity, we will choose common disorders to illustrate the diagnostic benefits and limitations of magnetic resonance imaging and provide reasons for choosing certain magnetic resonance imaging techniques. PMID- 22048193 TI - Effects of filtering methods on muscle and fat cross-sectional area measurement by pQCT: a technical note. AB - Peripheral quantitative computed tomography (pQCT) is most commonly used for bone density and morphology assessment of the limbs, but it can also be used for soft tissue area quantification by segmenting regions representing different tissues. Scanning and analyzing cross-sectional areas of larger thighs present a special challenge due to increased statistical noise created from fewer detected x-ray photons. The purpose of this technical note is to compare total, muscle and fat cross-sectional area (CSA) measurements of the midthigh with Stratec 3000 pQCT scans using no filter, a weak smoothing filter and a strong smoothing filter to CSA measurements of midthigh MRI scans analyzed by Image J, a public domain image processing program. Nine healthy men and women participated in this study. CSAs did not differ significantly between MRI and strongly filtered pQCT images with per cent differences ranging from -3.1% for muscle to +6.5% for fat. The per cent difference in muscle CSA values between MRI and pQCT with the weak filter (-24.0 +/- 38.0%) or no filter (-44.9 +/- 22.7%) was strongly related to total thigh CSA (r = 0.78-0.92, p < 0.05). We propose that the midthigh can be assessed for soft tissue area measurements with pQCT, provided that strong smoothing filter is utilized. PMID- 22048195 TI - A global obesity industry. PMID- 22048196 TI - [Fifteen years with Oslo 96--what now?]. PMID- 22048194 TI - Exogenous or endogenous Toll-like receptor ligands: which is the MVP in tumorigenesis? AB - Toll-like receptors (TLRs) are a class of pattern recognition receptors sensing microbial components and triggering an immune response against pathogens. In addition to their role in anti-infection immunity, increasing evidence indicates that engagement of TLRs can promote cancer cell survival and proliferation, induce tumor immune evasion, and enhance tumor metastasis and chemoresistance. Recent studies have demonstrated that endogenous molecules or damage-associated molecular patterns released from damaged/necrotic tissues are capable of activating TLRs and that the endogenous ligands-mediated TLR signaling is implicated in the tumor development and affects the therapeutic efficacy of tumors. Since both exogenous and endogenous TLR ligands can initiate TLR signaling, which is the most valuable player in tumor development becomes an interesting question. Here, we summarize the effect of TLR signaling on the development and progression of tumors, and discuss the role of exogenous and endogenous TLR ligands in the tumorigenesis. PMID- 22048197 TI - Non-controlled observation studies. PMID- 22048199 TI - [Driver's license and seizures with loss of consciousness]. PMID- 22048202 TI - [Drug industry and double morals]. PMID- 22048203 TI - [Moro reflex remains an important tool]. PMID- 22048205 TI - Waiting for psychiatric treatment. PMID- 22048206 TI - [Paracetamol poisonings after the lifting of the place of sale restriction]. AB - BACKGROUND: Before 2003, the sale of paracetamol in Norway was restricted to pharmacies only. In November 2003 this place of sale restriction was lifted, allowing sale of paracetamol in non-pharmacy locations. The purpose of this study was to investigate the incidence, severity and mortality of paracetamol poisoning before and after the lifting of the place of sale restriction. MATERIAL AND METHODS: Incidence was assessed using discharge data from three selected hospitals and the enquiry database of the National Poisons Information Centre (PIC). Evaluation of poisoning severity was based on degree of hepatotoxicity in admitted patients, number of requests regarding evaluation for liver transplantation at the National Transplantation Unit and PIC severity grading of cases. Data regarding mortality of paracetamol poisoning was obtained from the National Cause of Death Register. Data for the two-year period before (2001-2002) the place of sale restriction was lifted was compared with two years after (2005 2006). RESULTS: There was no significant change in the number of hospital admissions due to paracetamol poisoning in any of the three hospitals following the lifting of the place of sale restriction. The number of inquiries to PIC regarding paracetamol intake showed a statistical significant increase. The extent of severe paracetamol poisoning might be rising, but the mortality of paracetamol poisoning does not appear to have increased since the place of sale restriction was lifted. INTERPRETATION: There is no evidence that the number of paracetamol poisonings or deaths has increased since the place of sale restriction was lifted. The proportion of patients with liver toxicity/liver damage, and the number of patients evaluated for liver transplantation may be increasing. However, the development in paracetamol poisoning should be monitored in the coming years. PMID- 22048207 TI - [Smoking ban in restaurants and respiratory symptoms among employees]. AB - BACKGROUND: Along with the introduction of a smoking ban in restaurants in 2004, respiratory symptoms, urinary cotinine and lung function among employees in 13 different bars and restaurants were studied before and after the ban came into force. At the same time measurements of air quality were taken at the respective restaurants and bars. The purpose of this study was to compare self-respiratory symptoms before and after the smoking ban among the staff at the establishments. MATERIAL AND METHODS: The study included 93 men and women. These were followed during a work-shift before the smoking ban and three to eight months later. Initially 86 of the participants answered a questionnaire about respiratory tract symptoms , while 67 did so at follow-up. RESULTS: Before the ban 39 of the subjects (45.3%) reported wheezing in the chest and 28 (32.6%) said they had recently had an upper respiratory tract infection. 43.3% of the participants reported fewer symptoms and 20.9% more symptoms after the ban, while 35.8% reported no change. The corresponding figures among smokers were 47.5%, 15.0% and 37.5%. INTERPRETATIONS: This study shows that the introduction of a smoking ban in restaurants contributes to a reduction in reported respiratory symptoms among employees, and may therefore be advantageous for the health of this group. PMID- 22048208 TI - [Abuse of gamma-hydroxybutyrate]. AB - BACKGROUND: Gamma-hydroxybutyrate (GHB) is naturally present in the human body, but may also be used as an intoxicating drug. Information from several sources has suggested its increased availability and use in Norway. There have also been reports of an increasing use of the chemical precursor gamma-butyrolactone (GBL).There is currently a need for knowledge on symptoms, addictiveness and overdoses, as well as targeted preventive measures. MATERIAL AND METHODS: The article is based on a discretionary selection of articles resulting from a literature search in PubMed, as well as reports from Norwegian and European authorities and research institutions. RESULTS: An intake of small amounts of GHB produces an intoxicating effect, whereas higher doses can result in poisoning. Deaths have been reported. The effect may be variable, due to a steep dose response curve and interaction with alcohol and other intoxicants. Treatment of poisoning is symptomatic and supportive. Treatment of abstinence is also supportive, while delirium may be treated as delirium tremens. INTERPRETATION: Preventive measures should be tailored specifically to potential user-groups. PMID- 22048209 TI - [New gene map for multiple sclerosis]. AB - BACKGROUND: Multiple sclerosis (MS) is a demyelinating, inflammatory disease of the central nervous system which affects young adults with a relapsing or progressive disease course. The etiology of the disease is unknown, but both environmental and genetic factors contribute to the risk of developing MS. MATERIAL AND METHODS: We give an overview of new knowledge of the genetic risk factors for MS, based on our own work as well as on literature in this field. RESULTS: Through genome-wide association studies and subsequent replication studies a series of novel MS genes have recently been identified, in addition to the HLA association previously described. The International MS Genetics Consortium in collaboration with the Wellcome Trust Case Control Consortium recently published a genome-wide study of 9,722 MS patients and 17,376 controls. Genome-wide significant association (p < 10-8) was observed for 29 new as well as 23 previously identified gene regions, in addition to the HLA-DRB1 and -A loci .The majority of these MS-associated regions encode immune-related molecules. CONCLUSION: Genetic studies of large patient and control samples obtained through international and national collaborations have identified a list of more than 50 MS risk-gene regions, in addition to HLA-DRB1 and -A loci. The risk associated with each of these loci is low, however, they collectively point to the importance of immune-related pathways in the etiology of MS. PMID- 22048210 TI - [A bottle with unknown content]. PMID- 22048211 TI - [Baclofen for alcohol addiction]. AB - Baclofen is approved for muscle spasms and cerebral spasticity. Several studies have recently investigated the use of baclofen for alcohol withdrawal symptoms and as an abstinence-promoting agent in alcohol-dependent subjects. The evidence is too weak to recommend baclofen for alcohol withdrawal, and drugs with better documentation such as benzodiazepines and carbamazepine should be preferred for this indication. The evidence for the use of baclofen to prevent relapse to drinking in alcohol dependence is somewhat conflicting, but the drug could be considered as a therapeutic option in case of conservative measures and approved drugs such as disulfiram and acamprosate having insufficient effect. Despite enthusiastic appraisal in case reports, the use of baclofen in high doses to suppress alcohol craving cannot be recommended due to insufficient evidence. Trials that may resolve this issue are underway. PMID- 22048212 TI - A man in his 30s with recurrent vomiting and abdominal pain relieved by hot showers. PMID- 22048213 TI - [From active and passive death help to euthanasia and withholding treatment]. PMID- 22048214 TI - [Norwegian aid to medical education in Malawi]. PMID- 22048217 TI - Synthesis and transport property of Cu(1.8)S as a promising thermoelectric compound. AB - Polycrystalline Cu(1.8)S compounds were fabricated by using a combined process of mechanical alloying and spark plasma sintering. The Cu(1.8)S sample with a second Cu(1.96)S phase and a lot of micro pores shows its maximum ZT value 0.5 at 673 K which is the highest value for p-type sulfide thermoelectric materials so far. PMID- 22048218 TI - Scalable strategies for the synthesis of well-defined copper metal and oxide nanocrystals. AB - This tutorial review highlights the most promising methods for the preparation of well-defined copper metal and oxide nanocrystals. These methodologies could be applied to other metals. We present the main synthetic strategies and associated mechanisms to control monodispersity, size, morphology and structure of metal and oxide nanomaterials which can adopt spherical, polyhedral, cubic, rod, wire, plate shapes and possibly hollow structures. We also consider the scale-up of the production of these nanocrystals, which is crucial for a wide range of potential applications such as catalysis, photovoltaics, electronics, optics and electrocatalysis. PMID- 22048219 TI - Overview of best practices in conducting comparative-effectiveness reviews. AB - Comparative-effectiveness research (CER) reviews translate mountains of evidence into manageable and meaningful messages to inform clinical practice. CER reviews also have the potential to shorten the pipeline between research and practice. Reaching these goals through CER reviews requires adherence to CER principles and procedures, as well as the use of appropriate quantitative methods, qualitative methods, and clinical judgment. Comprehensiveness, objectivity, transparency, scientific rigor, relevance, and responsiveness are the principles that underpin best practices in conducting a CER review. PMID- 22048220 TI - Prioritizing comparative-effectiveness research topics via stakeholder involvement: an application in COPD. AB - A major priority for funding agencies and researchers involved in comparative effectiveness research (CER) is to ensure that research questions will produce findings that are relevant and feasible to implement. In this article, we describe a process for involving experts and stakeholders in identifying and prioritizing CER studies, as illustrated by our experience in chronic obstructive pulmonary disease (COPD). PMID- 22048221 TI - Pharmacodynamic evaluation of clopidogrel plus PA32540: the Spaced PA32540 With Clopidogrel Interaction Gauging (SPACING) study. AB - PA32540 combines 325 mg enteric-coated (EC) aspirin (ASA) with 40 mg immediate release omeprazole; its influence on the antiplatelet effect of clopidogrel (C) is unknown. In this randomized, open-label study, subjects (n = 30) were treated with (i) 300 mg C + 325 mg ECASA followed by 75 mg C + 325 mg ECASA on days 2-7, (ii) 300 mg C + PA32540 followed by 75 mg C + PA32540 on days 2-7, or (iii) PA32540 in the morning + 300 mg C 10 h later on day 1 and PA32540 in the morning + 75 mg C 10 h later on days 2-7. We analyzed the noninferiority of PA32540 relative to ECASA, as defined by the upper bound of the 95% confidence interval <=10% for the difference in least-square means of platelet inhibition between the treatments. As compared to ECASA+C, synchronous treatment of PA32540+C was not noninferior, whereas the spacing strategy of PA32540+C was noninferior. Spacing the administration of PA32540 and clopidogrel lessens the interaction observed with synchronous administration; PA32540 administration with clopidogrel may be associated with a different antiplatelet profile. PMID- 22048222 TI - Approaches to Japanese dose evaluation in global drug development: factors that generate different dosages between Japan and the United States. AB - Drug development in Japan is shifting from a bridging strategy to a global strategy, and the number of multiregional trials in which Japan is included is increasing every year. The Japanese drug regulatory authority requires that data be collected in Japanese populations, and therefore dose-response studies of various drugs are frequently conducted in Japan. However, the current standard for adequate dose-finding processes may sometimes hinder the timely participation of Japan in these multiregional trials. We studied the development approaches and review patterns of 99 new molecular entities (NMEs) approved in 2003-2008 and have identified some common factors that result in differences in approved dosages in Japan as compared with other countries, such as dose-response study design, pharmacokinetics, and the timing of development. The findings of our research will serve as an initial information base on which to build an efficient global drug development strategy in Japan. PMID- 22048223 TI - Differences in pharmacological activities of the antioxidant flavonoid monoHER in humans and mice are caused by variations in its metabolic profile. AB - Despite its well-known cardiotoxicity, the anthracycline doxorubicin continues to be a widely used chemotherapeutic agent. The flavonoid 7-mono-O-(beta hydroxyethyl)-rutoside (monoHER) has shown protection against doxorubicin-induced cardiotoxicity in mice. However, this protection has not been observed in humans. This prompted us to investigate monoHER metabolism in humans and compare it with that in mice. Five healthy volunteers received monoHER by intravenous infusion. After infusion, bile fluid was collected, and the monoHER metabolites were identified by liquid chromatography-diode-array detection (LC-DAD), time-of flight mass spectrometry (TOF-MS), and (1)H-nuclear magnetic resonance (NMR). Thirteen different metabolites were identified. MonoHER was predominantly converted into inactive glucuronidated metabolites. In mice, the major metabolic route is methylation, which forms bioactive metabolites that are implicated in the cardioprotective effect of monoHER. This indicates that the different pharmacological effects of monoHER in mice and humans might be explained by a difference in monoHER metabolism. This study adds to the growing appreciation of flavonoid metabolites as bioactive compounds. PMID- 22048224 TI - Evidence of CYP3A allosterism in vivo: analysis of interaction between fluconazole and midazolam. AB - The allosteric effect of fluconazole (effector) on the formation of 1' hydroxymidazolam (1'-OH-MDZ) and 4-hydroxymidazolam (4-OH-MDZ) from midazolam (MDZ), a substrate of CYP3A4/5--members of the cytochrome P450 superfamily of enzymes--was examined in healthy volunteers. Following pretreatment with fluconazole, the ratio of the areas under the curve (AUCs) for 4-OH-MDZ and MDZ (AUC(4-OH)/AUC(MDZ)) increased by 35-62%, whereas the ratio AUC(1'-OH)/AUC(MDZ) decreased by 5-37%; the ratio AUC(1'-OH)/AUC(4-OH) decreased by 46-58% after fluconazole administration and had no association with the CYP3A5 genotype. The in vitro formation of 1'-OH-MDZ was more susceptible to inhibition by fluconazole than that of 4-OH-MDZ. Fluconazole decreased the intrinsic formation-clearance ratio of 1'-OH-MDZ/4-OH-MDZ to an extent that was quantitatively comparable to in vivo observations. The elimination clearance of MDZ metabolites appeared unaffected by fluconazole. This study demonstrated that fluconazole alters formation of MDZ metabolites, both in vivo and in vitro, in a manner consistent with an allosteric interaction. The 1'-OH-MDZ/4-OH-MDZ ratio may serve as a biomarker of such interactions among MDZ, CYP3A4/5, and other putative effectors. PMID- 22048225 TI - Cannabinoid-opioid interaction in chronic pain. AB - Cannabinoids and opioids share several pharmacologic properties and may act synergistically. The potential pharmacokinetics and the safety of the combination in humans are unknown. We therefore undertook a study to answer these questions. Twenty-one individuals with chronic pain, on a regimen of twice-daily doses of sustained-release morphine or oxycodone were enrolled in the study and admitted for a 5-day inpatient stay. Participants were asked to inhale vaporized cannabis in the evening of day 1, three times a day on days 2-4, and in the morning of day 5. Blood sampling was performed at 12-h intervals on days 1 and 5. The extent of chronic pain was also assessed daily. Pharmacokinetic investigations revealed no significant change in the area under the plasma concentration-time curves for either morphine or oxycodone after exposure to cannabis. Pain was significantly decreased (average 27%, 95% confidence interval (CI) 9, 46) after the addition of vaporized cannabis. We therefore concluded that vaporized cannabis augments the analgesic effects of opioids without significantly altering plasma opioid levels. The combination may allow for opioid treatment at lower doses with fewer side effects. PMID- 22048226 TI - Assessing the probability of drug-induced QTc-interval prolongation during clinical drug development. AB - Early in the course of clinical development of new non-antiarrhythmic drugs, it is important to assess the propensity of these drugs to prolong the QT/QTc interval. The current regulatory guidelines suggest using the largest time matched mean difference between drug and placebo (baseline-adjusted) groups over the sampling interval, thereby neglecting any potential exposure-effect relationship and nonlinearity in the underlying physiological fluctuation in QT values. Thus far, most of the attempted models for characterizing drug-induced QTc-interval prolongation have disregarded the possibility of model parameterization in terms of drug-specific and system-specific properties. Using a database consisting of three compounds with known dromotropic activity, we built a bayesian hierarchical pharmacodynamic (PD) model to describe QT interval, encompassing an individual correction factor for heart rate, an oscillatory component describing the circadian variation, and a truncated maximum-effect model to account for drug effect. The explicit description of the exposure-effect relationship, incorporating various sources of variability, offers advantages over the standard regulatory approach. PMID- 22048227 TI - A dose-response meta-analysis for quantifying relative efficacy of biologics in rheumatoid arthritis. AB - We present a dose-response meta-analysis to quantify relative efficacy of biologic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). There is a strong rationale for this analysis because, although multiple biologics are available, information on head-to-head comparisons is limited. Data on the percentage of patients attaining American College of Rheumatology (ACR) 20, 50, and 70 responses were extracted from 50 randomized controlled trials representing 21,500 patients, five mechanisms of action, and nine biologics. The analysis showed that all tumor necrosis factor inhibitors (anti-TNFs) share the same dose-response relationship for ACR 20, 50, and 70, differing only in potency. Yet there are significant differences in efficacy among the anti-TNFs due to differences in the clinical dose ranges available. At the suggested starting dose, golimumab was the least efficacious, followed by infliximab, adalimumab, etanercept, and certolizumab. Significant differences in the dose-response relationship were found between anti-TNFs and other biologics, resulting in differences in efficacy and differential impact of dose titration. PMID- 22048228 TI - Improving the decision-making process for nonprescription drugs: a framework for benefit-risk assessment. AB - Nonprescription drugs pose unique challenges to regulators. The fact that the barriers to access are lower for nonprescription drugs as compared with prescription drugs may permit additional consumers to obtain effective drugs. However, the use of these drugs by consumers in the absence of supervision by a health-care professional may result in unacceptable rates of misuse and suboptimal clinical outcomes. A value-tree method is proposed that defines important benefit and risk domains relevant to nonprescription drugs. This value tree can be used to comprehensively identify product-specific attributes in each domain and can also support formal benefit-risk assessment using a variety of tools. This is illustrated here, using a modification of the International Risk Governance Council (IRGC) framework, a flexible tool previously applied in a number of fields, which systematizes an approach to issue review, early alignment of stakeholders, evaluation, and risk mitigation/management. The proposed approach has the potential to provide structured, transparent tools for regulatory decision making for nonprescription drugs. PMID- 22048229 TI - Geranylgeranyl diphosphate synthase: an emerging therapeutic target. AB - Proteins modified post-translationally by geranylgeranylation have been implicated in numerous cellular processes related to human disease. In recent years, the study of protein geranylgeranylation has advanced tremendously in both cellular and animal models. The advances in our understanding of the biological roles of geranylgeranylated proteins have been paralleled by advances in the medicinal chemistry of geranylgeranylation inhibitors such as those that target geranylgeranyl transferases I and II and geranylgeranyl diphosphate synthase (GGDPS). Although these findings provide the rationale for further development of geranylgeranylation as a therapeutic target, more advanced studies on the efficacy of this approach in various disease models will be required to support translation to clinical studies. This article attempts to describe the advances in (and the challenges of) validation of GGDPS as a novel therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. PMID- 22048230 TI - Assessing the comparative effectiveness of newly marketed medications: methodological challenges and implications for drug development. AB - Comparative-effectiveness research (CER) aims to produce actionable evidence regarding the effectiveness and safety of medical products and interventions as they are used outside of controlled research settings. Although CER evidence regarding medications is particularly needed shortly after market approval, key methodological challenges include (i) potential bias due to channeling of patients to the newly marketed medication because of various patient-, physician , and system-related factors; (ii) rapid changes in the characteristics of the user population during the early phase of marketing; and (iii) lack of timely data and the often small number of users in the first few months of marketing. We propose a mix of approaches to generate comparative-effectiveness data in the early marketing period, including sequential cohort monitoring with secondary health-care data and propensity score (PS) balancing, as well as extended follow up of phase III and phase IV trials, indirect comparisons of placebo-controlled trials, and modeling and simulation of virtual trials. PMID- 22048231 TI - Therapeutic index of anticoagulants for prevention of venous thromboembolism following orthopedic surgery: a dose-response meta-analysis. AB - Information on the comparative effectiveness of drugs is crucial for drug development decisions, in addition to being needed by regulators, prescribers, and payers. We have carried out a dose-response meta-analysis of three end points each for efficacy and bleeding for various anticoagulants evaluated for the prevention of venous thromboembolism (VTE) following orthopedic surgery to assess the comparative efficacy and safety of various classes of agents. Data obtained from 89 randomized controlled trials of 23 anticoagulants representing seven drug classes were analyzed. The analysis showed significant differences in the therapeutic index (TI), the ratio of the dose with an acceptable bleeding risk to the dose with a relevant risk reduction for VTE, across the drug classes but not for drugs within a class. The direct inhibitors of FXa, the activated form of factor X--also known as prothrombinase--were found to have a significantly higher TI than that of any other class of anticoagulants, including enoxaparin, suggesting that this mechanism of action provides the best safety-to-efficacy margin. PMID- 22048232 TI - Comparisons of persistence and durability among three oral antidiabetic therapies using electronic prescription-fill data: the impact of adherence requirements and stockpiling. AB - Two important challenges are inherent in the design of studies using prescription data from electronic health records: how to define the minimum level of adherence that would qualify as "continuous drug use" and how to handle stockpiling of medications. Generally, the sensitivity of a study's conclusions to these design choices is not analyzed. In our study, covariate adjusted Cox models were used to compare persistence and durability with respect to three common oral antidiabetic therapies in a cohort of 12,697 incident users. Assuming 50% stockpiling, sulfonylurea therapy, as compared with metformin, showed a significantly lower risk of nonpersistence (changing or stopping therapy) when no gap days were allowed (HR 0.95, P = 0.032), no significant difference when 14 gap days were allowed (HR 0.99, P = 0.536), and significantly greater risk of nonpersistence when 30 gap days were allowed (HR 1.05, P = 0.046). All the drug comparisons showed statistically significant effects in both directions, the risk of nonpersistence increasing or decreasing depending on the design parameters. PMID- 22048233 TI - Combining different analytical approaches to identify odor formation mechanisms in polyethylene and polypropylene. AB - In a previous study, we identified carbonyls as highly odor-active compounds in both unprocessed and processed polypropylene (PP) with higher intensities after processing, indicating a temperature-driven forming mechanism. In the presented work, we studied whether (a) these carbonyls are the major odor drivers to the overall odor of polyolefins, (b) their formation is taking place already at moderate temperatures well below the typical processing temperatures, (c) conventional antioxidants in polyolefins can prevent or reduce their formation, and (d) whether reducing the amount of oxygen present can decrease the overall odor. One polyethylene (PE) and one PP were selected, and both stabilized and unstabilized polymer powder samples were exposed to conditions differing in oxygen concentration and aging time. The changes in the volatile fraction as well as the formation of odor-active compounds were monitored using a multidisciplinary approach by combining analytical methods based on gas chromatography (GC), multivariate data analysis, and sensory methods (GC olfactometry and a sensory panel). Both investigated materials (PE and PP) showed similar degradation products (aldehydes, ketones, carboxylic acids, alcohols, and lactones) which increased dramatically with increasing aging time and the lack of stabilization. Oxidation products, mainly carbonyl compounds, were responsible for the odor of the investigated materials. The main odor drivers were unsaturated ketones and aldehydes with a chain length between six and nine C atoms. Interestingly, similar odor patterns were found for both stabilized and unstabilized samples, indicating that similar formation processes take place independent of the stabilization. PMID- 22048236 TI - Target-induced conjunction of split aptamer as new chiral selector for oligopeptide on graphene-mesoporous silica-gold nanoparticle hybrids modified sensing platform. AB - A new electrochemical label-free biosensor based on target-induced conjunction of a split aptamer as new chiral selector for oligopeptide using graphene-mesoporous silica-gold NP hybrids (GSGHs) as magnified sensing platform is firstly reported, which showed high sensitivity and selectivity for the detection of D-vasopressin (D-VP). PMID- 22048237 TI - Phase II, open-label, randomized trial of the MEK1/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. AB - PURPOSE: To compare the efficacy and tolerability of the mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase (MEK) 1/2 inhibitor selumetinib versus temozolomide in chemotherapy-naive patients with unresectable stage III/IV melanoma. EXPERIMENTAL DESIGN: This phase II, open-label, multicenter, randomized, parallel-group study examined the effect of 100 mg oral selumetinib twice daily in 28-day cycles versus oral temozolomide (200 mg/m(2)/d for 5 days, then 23 days off-treatment). The primary endpoint was progression free survival. RESULTS: Two hundred patients were randomized. Progression-free survival did not differ significantly between selumetinib and temozolomide (median time to event 78 and 80 days, respectively; hazard ratio, 1.07; 80% confidence interval, 0.86-1.32). Objective response was observed in six (5.8%) patients receiving selumetinib and nine (9.4%) patients in the temozolomide group. Among patients with BRAF mutations, objective responses were similar between selumetinib and temozolomide groups (11.1% and 10.7%, respectively). However, five of the six selumetinib partial responders were BRAF mutated. Frequently reported adverse events with selumetinib were dermatitis acneiform (papular pustular rash; 59.6%), diarrhea (56.6%), nausea (50.5%), and peripheral edema (40.4%), whereas nausea (64.2%), constipation (47.4%), and vomiting (44.2%) were reported with temozolomide. CONCLUSIONS: No significant difference in progression-free survival was observed between patients with unresectable stage III/IV melanoma unselected for BRAF/NRAS mutations, who received therapy with selumetinib or temozolomide. Five of six patients with partial response to selumetinib had BRAF mutant tumors. PMID- 22048238 TI - Phenylarsine oxide induces apoptosis in Bax- and Bak-deficient cells through upregulation of Bim. AB - PURPOSE: Bax and Bak are regarded as key mediators for cytochrome c (Cyt c) release and apoptosis. Loss of Bax or Bak is often reported in human cancers and renders resistance of these cancerous cells to chemotherapy. Here, we investigated that phenylarsine oxide (PAO) could induce Bax/Bak-independent apoptosis. EXPERIMENTAL DESIGN: Annexin V/propidium iodide (PI) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and caspase activation assays were conducted to detect apoptosis in Bax/Bak-deficient mouse embryonic fibroblasts (MEF) and HCT116 bax(-/-) colorectal cancer cells. Cyt c release and Bim expression were assessed by Western blotting and immunostaining. Bim was stably knocked down by short hairpin RNA. Immunoprecipitation was applied to detect the interaction between Bim and Bcl-2. Both subcutaneous and colorectal orthotopic tumor implantation models were used in nude mice to investigate the effect of PAO in vivo. RESULTS: PAO triggered Cyt c release and apoptosis in a Bax/Bak-independent manner. Bim and Bcl-2 were both involved in this process. PAO augmented the expression of Bim and strengthened the interaction between Bim and Bcl-2. Furthermore, PAO attenuated the growth of Bax-deficient cancer cells in vivo. CONCLUSIONS: Our results showed that PAO induced apoptosis in chemotherapy-resistant cancer cells, which suggests that PAO has the potential to serve as a chemotherapeutic agent for Bax- and Bak deficient cancers. PMID- 22048239 TI - IL-22, but not IL-17, dominant environment in cutaneous T-cell lymphoma. AB - PURPOSE: Both patients with cutaneous T-cell lymphoma (CTCL) and those with atopic dermatitis (AD) have pruritus, T(H)2-biased T cells, and a tendency to have bacterial infections, suggesting a common pathologic basis for these two diseases. Recently, interleukin (IL)-22-producing T cells were reported in skin of patients with AD. In this study, we investigated expression levels of T(H)22- and T(H)17-related molecules in lesional skin and sera isolated from patients with CTCL. EXPERIMENTAL DESIGN: Skin biopsies and sera were collected from patients with CTCL or psoriasis and from healthy volunteers. Protein and mRNA expression levels of IL-22, IL-17A, IL-17F, IL-23p19, IL-10, IL-4, CCL20, CCR6, IL-8, and IL-20 were examined in lesional tissue and a subset of these molecules in sera. Phosphorylation of STAT3 was also assessed in lesional skin of CTCL and psoriasis by immunohistochemistry. RESULTS: IL-22, IL-10, IL-4, CCL20, and CCR6 mRNA and protein levels, but not IL-17A, IL-17F, IL-23p19, IL-8, or IL-20, were significantly elevated in lesional skin of CTCL. Phosphorylation of STAT3 was detected in epidermis of CTCL skin. Moreover, serum IL-22, IL-10, and CCL20 levels were increased in CTCL and correlated with disease severity. CONCLUSIONS: Our results suggest that IL-22 is important in establishing the tumor microenvironment for CTCL. Enhanced expression of CCL20 may explain epidermal hyperplasia and migration of CCR6(+) cells, such as Langerhans cells, into lesional skin. Relatively low expression of IL-17 may explain the lack of neutrophils in lesions of CTCL, which correlates with bacterial infections that commonly occur in skin affected by CTCL. PMID- 22048240 TI - NKX3.1 haploinsufficiency is prognostic for prostate cancer relapse following surgery or image-guided radiotherapy. AB - BACKGROUND: Despite the use of prostate specific antigen (PSA), Gleason-score, and T-category as prognostic factors, up to 40% of patients with intermediate risk prostate cancer will fail radical prostatectomy or precision image-guided radiotherapy (IGRT). Additional genetic prognosticators are needed to triage these patients toward intensified combination therapy with novel targeted therapeutics. We tested the role of the NKX3.1 gene as a determinant of treatment outcome given its reported roles in tumor initiating cell (TIC) renewal, the DNA damage response, and cooperation with c-MYC during prostate cancer progression. METHODS: Using high-resolution array comparative genomic hybridization (aCGH), we profiled the copy number alterations in TIC genes using tumor DNA from frozen needle biopsies derived from 126 intermediate-risk patients who underwent IGRT. These data were correlated to biochemical relapse-free rate (bRFR) by the Kaplan Meier method and Cox proportional hazards models. RESULTS: A screen of the aCGH IGRT data for TIC genes showed frequent copy number alterations for NKX3.1, PSCA, and c-MYC. NKX3.1 haploinsufficiency was associated with increased genomic instability independent of PSA, T-category, and Gleason-score. After adjusting for clinical factors in a multivariate model, NKX3.1 haploinsufficiency was associated with bRFR when tested alone (HR = 3.05, 95% CI: 1.46-6.39, P = 0.0030) or when combined with c-MYC gain (HR = 3.88, 95% CI: 1.78-8.49, P = 0.00067). A similar association was observed for patients following radical prostatectomy with a public aCGH database. NKX3.1 status was associated with positive biopsies post-IGRT and increased clonogen radioresistance in vitro. CONCLUSIONS: Our results support the use of genomic predictors, such as NKX3.1 status, in needle biopsies for personalized approaches to prostate cancer management. PMID- 22048241 TI - Serum Interleukin-6, insulin, and HOMA-IR in male individuals with colorectal adenoma. AB - PURPOSE: It is widely acknowledged that chronic low-grade inflammation plays a key role in the development of obesity-related insulin resistance and type 2 diabetes. The level of circulating interleukin-6 (IL-6), one of the major proinflammatory adipokines, is correlated with obesity and insulin resistance, which are known to be risk factors for colorectal adenoma. We examined the association between the circulating level of IL-6 and the presence of colorectal adenoma. EXPERIMENTAL DESIGN: In a total colonoscopy-based cross-sectional study conducted between January and December 2008, serum levels of IL-6 were measured in samples of venous blood obtained from 336 male participants attending health checkups (118 individuals with colorectal adenoma and 218 age-matched controls) after an overnight fast. RESULTS: In the colorectal adenoma group, the median levels of serum IL-6 (1.24 vs. 1.04 pg/mL; P = 0.01), triglyceride, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were to be significantly higher than those in the control group. When restricted to individuals with adenoma, levels of IL-6 were positively correlated with body mass index, insulin, and HOMA-IR. Multiple logistic analyses adjusted to include insulin or HOMA-IR showed that high levels of IL-6 were associated with the presence of colorectal adenoma. There was no significant interaction of IL-6 with HOMA-IR to modify this association. CONCLUSIONS: Our findings suggest that increased serum levels of IL-6 are positively associated with the presence of colorectal adenoma in men, independently of insulin and HOMA-IR. PMID- 22048242 TI - Compact and autonomous multiwavelength microanalyzer for in-line and in situ colorimetric determinations. AB - Nowadays, the attainment of microsystems that integrate most of the stages involved in an analytical process has raised an enormous interest in several research fields. This approach provides experimental set-ups of increased robustness and reliability, which simplify their application to in-line and continuous biomedical and environmental monitoring. In this work, a novel, compact and autonomous microanalyzer aimed at multiwavelength colorimetric determinations is presented. It integrates the microfluidics (a three-dimensional mixer and a 25 mm length "Z-shape" optical flow-cell), a highly versatile multiwavelength optical detection system and the associated electronics for signal processing and drive, all in the same device. The flexibility provided by its design allows the microanalyzer to be operated either in single fixed mode to provide a dedicated photometer or in multiple wavelength mode to obtain discrete pseudospectra. To increase its reliability, automate its operation and allow it to work under unattended conditions, a multicommutation sub-system was developed and integrated with the experimental set-up. The device was initially evaluated in the absence of chemical reactions using four acidochromic dyes and later applied to determine some key environmental parameters such as phenol index, chromium(VI) and nitrite ions. Results were comparable with those obtained with commercial instrumentation and allowed to demonstrate the versatility of the proposed microanalyzer as an autonomous and portable device able to be applied to other analytical methodologies based on colorimetric determinations. PMID- 22048243 TI - Effects of all-trans retinoic acid nanoparticles on corneal epithelial wound healing. AB - BACKGROUND: We have developed inorganically-coated all-trans retinoic acid (atRA) nanoparticles, nano-sized egg-like particles of atRA (NANOEGG(r)-atRA). The purpose of this study was to determine the effects of NANOEGG(r)-atRA on corneal wound healing in vivo and in vitro. METHODS: A rabbit corneal epithelial wound healing model was exposed to different concentrations of NANOEGG(r)-atRA. Wound healing was serially quantified as the ratio of fluorescein-stained area at the selected times to that at baseline. After wound closure, the barrier function of the cornea was determined using low concentrations of tropicamide. At the completion of the experiments, the corneal epithelium was histologically examined. For the in vitro studies, linear scratch wounds were made on cultured SV40-immortalized human corneal epithelial cells (HCE-T). Then, the cells were exposed to different concentrations of NANOEGG(r)-atRA, and wound healing was determined by the degree of closure of the scratch wound. In addition, the effects of NANOEGG(r)-atRA on the proliferation of HCE-T cells were determined by WST-8 assays. RESULTS: Exposure to NANOEGG(r)-atRA decreased the injured area 24 hrs after the ablation. The maximum effect of NANOEGG(r)-atRA was observed at a concentration of 33 mM. Histologically, no abnormal or differentiated corneal epithelial cells were observed in the histological sections treated with NANOEGG(r)-atRA. The tropicamide-induced pupillary dilation was significantly slowed in the eyes treated with NANOEGG(r)-atRA. NANOEGG(r)-atRA at concentrations of 3.3 and 33 nM induced earlier wound closure in vitro, but did not induce proliferation of HCE-T cells. CONCLUSION: NANOEGG(r)-atRA promotes wound healing and should be considered for the treatment of wounds of the corneal epithelium. PMID- 22048245 TI - Misleading axial length measurements with the IOLMaster due to a dense posterior vitreous surface membrane and a macular edema in a diabetic patient. PMID- 22048244 TI - Endophthalmitis following intravitreal injections. AB - BACKGROUND: To report the clinical features, culture results, management and visual outcome of patients with endophthalmitis following intravitreal injections. METHODS: Retrospective review of all patients with suspected endophthalmitis after intravitreal injections treated with intravitreal antibiotics (teicoplanin and ciprofloxacin) at a referral centre between January 2003 and December 2010. RESULTS: Nineteen cases that had aqueous or vitreous biopsy were identified. Nine had negative culture. Ten had positive culture; Staphylococcus species in 4/10, Streptococcus species in 4/10, E. coli in 1/10 and gram-negative bacilli in 1/10. Symptoms developed within the first 48 hours in all. One of ten culture-positive cases had no pain on presentation, while 5/9 patients with negative culture reported pain. Initial treatment consisted of intravitreal antibiotics in all cases, 6/19 cases required a second intravitreal antibiotic injection, 4/19 underwent vitrectomy as secondary therapy. At the last follow up, 7/19 patients had visual acuity of 6/18 or better, 9/19 had visual acuity of 6/60 or worse. CONCLUSION: The overall numbers of patients with endophthalmitis following intravitreal injections has risen dramatically over the past years. In contrast to earlier reports of multicentre studies, outcome of patients is relatively poor in the current treatment settings. We did not find clinical features useful in identifying cases with negative culture. PMID- 22048246 TI - Expression of human NAA11 (ARD1B) gene is tissue-specific and is regulated by DNA methylation. AB - NAA10 gene encodes the catalytic subunit of N(alpha)-acetyltransferase NatA that catalyzes the acetylation of the N-termini of many eukaryotic proteins. A homologous gene called NAA11 is also present in mammalian cells. hNaa10p and hNaa11p are reported to be co-expressed in human cell cultures. In mouse tissues, however, Naa11 transcripts can only be detected in gonadal tissues whereas Naa10 transcripts are present in various tissues. We re-examined the expression of NAA11 in human cell lines and expanded the test to normal as well as cancerous human tissues. Surprisingly, we did not detect the expression of NAA11 in human cell lines that previously were reported to express it. Similar to its mouse ortholog, NAA10 displayed widespread expression in human tissues. NAA11 transcripts, however, were only detected in testicular and placental tissues. The lack of NAA11 expression was also demonstrated in eight different types of human cancerous tissues. By methylation-specific polymerase chain reaction and bisulfite sequencing, we found that the absence of NAA11 expression correlated with hypermethylation of the CpG island located at the proximal promoter of NAA11 gene. We also found that the cloned NAA11 gene promoter fragment was active when introduced into non NAA11-expressing human cells and its promoter activity was lost upon in vitro DNA methylation. Taken together, our results indicate NAA11 expression is tissue-specific and is epigenetically regulated by DNA methylation. PMID- 22048247 TI - Adaptation of the CHARM DNA methylation platform for the rat genome reveals novel brain region-specific differences. AB - Comprehensive High-throughput Arrays for Relative Methylation (CHARM) was recently developed as an experimental platform and analytic approach to assess DNA methylation (DNAm) at a genome-wide level. Its initial implementation was for human and mouse. We adapted it for rat and sought to examine DNAm differences across tissues and brain regions in this model organism. We extracted DNA from liver, spleen, and three brain regions: cortex, hippocampus, and hypothalamus from adult Sprague Dawley rats. DNA was digested with McrBC, and the resulting methyl-depleted fraction was hybridized to the rat CHARM array along with a mock treated fraction. Differentially methylated regions (DMRs) between tissue types were detected using normalized methylation log-ratios. In validating 24 of the most significant DMRs by bisulfite pyrosequencing, we detected large mean differences in DNAm, ranging from 33-59%, among the most significant DMRs in the across-tissue comparisons. The comparable figures for the hippocampus vs. hypothalamus DMRs were 14-40%, for the cortex vs. hippocampus DMRs, 12-29%, and for the cortex vs. hypothalamus DMRs, 5-35%, with a correlation of r(2) = 0.92 between the methylation differences in 24 DMRs predicted by CHARM and those validated by bisulfite pyrosequencing. Our adaptation of the CHARM array for the rat genome yielded highly robust results that demonstrate the value of this method in detecting substantial DNAm differences between tissues and across different brain regions. This platform should prove valuable in future studies aimed at examining DNAm differences in particular brain regions of rats exposed to environmental stimuli with potential epigenetic consequences. PMID- 22048248 TI - Bivalent histone modifications in stem cells poise miRNA loci for CpG island hypermethylation in human cancer. AB - It has been proposed that the existence of stem cell epigenetic patterns confer a greater likelihood of CpG island hypermethylation on tumor suppressor-coding genes in cancer. The suggested mechanism is based on the Polycomb-mediated methylation of K27 of histone H3 and the recruitment of DNA methyltransferases on the promoters of tumor suppressor genes in cancer cells, when those genes are preferentially pre-marked in embryonic stem cells (ESCs) with bivalent chromatin domains. On the other hand, miRNAs appear to be dysregulated in cancer, with many studies reporting silencing of miRNA genes due to aberrant hypermethylation of their promoter regions. We wondered whether a pre-existing histone modification profile in stem cells might also contribute to the DNA methylation-associated silencing of miRNA genes in cancer. To address this, we examined a group of tumor suppressor miRNA genes previously reported to become hypermethylated and inactivated specifically in cancer cells. We analyzed the epigenetic events that take place along their promoters in human embryonic stem cells and in transformed cells. Our results suggest that there is a positive correlation between the existence of bivalent chromatin domains on miRNA promoters in ESCs and the hypermethylation of those genes in cancer, leading us to conclude that this epigenetic mark could be a mechanism that prepares miRNA promoters for further DNA hypermethylation in human tumors. PMID- 22048249 TI - DNA methylation imprinting marks and DNA methyltransferase expression in human spermatogenic cell stages. AB - Paternal imprinting marks were shown to be erased in the mouse primordial germ cells and progressively re-established throughout the male germ line development, starting in fetal prospermatogonia and continuing post-natally through the onset of meiosis. We here evaluated imprinting marks in human adult spermatogenic cells and analyzed mRNA and protein expression of DNA Methyltransferases (DNMTs). Spermatogonia A, primary and secondary spermatocytes, round spermatids and elongated spermatids/spermatozoa were isolated by micromanipulation from testicular biopsies of men with normal spermatogenesis. DNA methylation at two imprinted genes, H19 and MEST/PEG1, was analyzed using bisulphite genomic sequencing and DNMTs expression was determined by qRT-PCR and immunofluorescence. H19 was completely methylated at the spermatogonia stage in the analyzed individuals and MEST/PEG1 was completely demethylated, with the exception of few CpGs. The analysis of DNMT1, DNMT3A and 3B expression showed peaks of mRNA transcripts in primary spermatocytes and in mature ejaculated spermatozoa, with DNMT1 transcript level being the most abundant in all cell stages. Immunolocalization showed that DNMT proteins are present throughout the spermatogenic cycle, with stage-specific shuttling between the nucleus and cytoplasm. We conclude that, in humans, methylation imprints are established in spermatogonia A and are maintained in subsequent stages up to elongated spermatid/spermatozoa. Additionally, DNA methyltransferases are expressed throughout human spermatogenesis, possibly maintaining the methylation patterns in order to avoid the transmission of imprinting errors by the male gamete. PMID- 22048250 TI - Maintenance of DNA methylation: Dnmt3b joins the dance. AB - DNA methylation mostly occurs within the context of CpG dinucleotides and is essential for embryonic development and gene repression. It is generally accepted that DNA methyltransferases carry out specific and non-overlapping functions, Dnmt3a and Dnmt3b being responsible for the establishment of methylation around the time of implantation and Dnmt1 ensuring that methylation is faithfully copied to daughter cells via what has come to be known as "maintenance methylation." This longstanding view has been challenged over the years with the observation that Dnmt1 alone is incapable of perfect maintenance methylation. A new model is emerging that takes into account a contribution of the de novo enzymes Dnmt3a and Dnmt3b in the maintenance of the DNA methylation. We recently showed that certain germ line genes are specific targets of Dnmt3b, and that Dnmt3b remains bound to their promoter regions in somatic cells via interaction with the transcriptional repressor E2F6. It is tempting to consider an ongoing role for Dnmt3b in the methylation of germ line genes in somatic cells. We propose here observations in support of the hypothesis that the maintenance of methylation and subsequent silencing of a handful of germ line genes requires Dnmt3b but not Dnmt1. In addition to suggesting a new role for Dnmt3b in the protection of somatic cells against the promiscuous expression of the germ line program, these observations are of particular interest in the field of carcinogenesis, given that the expression of catalytically inactive Dnmt3b isoforms and aberrant expression of germ line genes are commonly observed in cancer cells. PMID- 22048251 TI - DNA methylation in liver tumorigenesis in fish from the environment. AB - The link between environment, alteration in DNA methylation and cancer has been well established in humans; yet, it is under-studied in unsequenced non-model organisms. The occurrence of liver tumors in the flatfish dab collected at certain UK sampling sites exceeds 20%, yet the causative agents and the molecular mechanisms of tumor formation are not known, especially regarding the balance between epigenetic and genetic factors. Methylated DNA Immunoprecipitation (MeDIP) combined with de novo high-throughput DNA sequencing were used to investigate DNA methylation changes in dab hepatocellular adenoma tumors for the first time in an unsequenced species. Novel custom-made dab gene expression arrays were designed and used to determine the relationship between DNA methylation and gene expression. In addition, the confirmatory techniques of bisulfite sequencing PCR (BSP) and RT-PCR were applied. Genes involved in pathways related to cancer, including apoptosis, wnt/beta-catenin signaling and genomic and non-genomic estrogen responses, were altered both in methylation and transcription. Global methylation was statistically significantly 1.8-fold reduced in hepatocellular adenoma and non-cancerous surrounding tissues compared with liver from non-cancer bearing dab. Based on the identified changes and chemical exposure data, our study supports the epigenetic model of cancer. We hypothesize that chronic exposure to a mixture of environmental contaminants contributes to a global hypomethylation followed by further epigenetic and genomic changes. The findings suggest a link between environment, epigenetics and cancer in fish tumors in the wild and show the utility of this methodology for studies in non-model organisms. PMID- 22048252 TI - Role of CpG context and content in evolutionary signatures of brain DNA methylation. AB - DNA methylation is essential in brain function and behavior; therefore, understanding the role of DNA methylation in brain-based disorders begins with the study of DNA methylation profiles in normal brain. Determining the patterns and scale of methylation conservation and alteration in an evolutionary context enables the design of focused but effective methylation studies of disease states. We applied an enzymatic-based approach, Methylation Mapping Analysis by Paired-end Sequencing (Methyl-MAPS), which utilizes second-generation sequencing technology to provide an unbiased representation of genome-wide DNA methylation profiles of human and mouse brains. In this large-scale study, we assayed CpG methylation in cerebral cortex of neurologically and psychiatrically normal human postmortem specimens, as well as mouse forebrain specimens. Cross-species human mouse DNA methylation conservation analysis shows that DNA methylation is not correlated with sequence conservation. Instead, greater DNA methylation conservation is correlated with increasing CpG density. In addition to CpG density, these data show that genomic context is a critical factor in DNA methylation conservation and alteration signatures throughout mammalian brain evolution. We identify key genomic features that can be targeted for identification of epigenetic loci that may be developmentally and evolutionarily conserved and wherein aberrations in DNA methylation patterns can confer risk for disease. PMID- 22048253 TI - Preferential binding of the methyl-CpG binding domain protein 2 at methylated transcriptional start site regions. AB - Methyl-CpG Binding Domain (MBD) proteins are thought to be key molecules in the interpretation of DNA methylation signals leading to gene silencing through recruitment of chromatin remodeling complexes. In cancer, the MBD-family member, MBD2, may be primarily involved in the repression of genes exhibiting methylated CpG at their 5' end. Here we ask whether MBD2 randomly associates methylated sequences, producing chance effects on transcription, or exhibits a more specific recognition of some methylated regions. Using chromatin and DNA immunoprecipitation, we analyzed MBD2 and RNA polymerase II deposition and DNA methylation in HeLa cells on arrays representing 25,500 promoter regions. This first whole-genome mapping revealed the preferential localization of MBD2 near transcription start sites (TSSs), within the region analyzed, 7.5 kb upstream through 2.45 kb downstream of 5' transcription start sites. Probe by probe analysis correlated MBD2 deposition and DNA methylation. Motif analysis did not reveal specific sequence motifs; however, CCG and CGC sequences seem to be overrepresented. Nonrandom association (multiple correspondence analysis, p < 0.0001) between silent genes, DNA methylation and MBD2 binding was observed. The association between MBD2 binding and transcriptional repression weakened as the distance between binding site and TSS increased, suggesting that MBD2 represses transcriptional initiation. This hypothesis may represent a functional explanation for the preferential binding of MBD2 at methyl-CpG in TSS regions. PMID- 22048254 TI - The influence of one-carbon metabolism on gene promoter methylation in a population-based breast cancer study. AB - Abnormal methylation in gene promoters is a hallmark of the cancer genome; however, factors that may influence promoter methylation have not been well elucidated. As the one-carbon metabolism pathway provides the universal methyl donor for methylation reactions, perturbation of this pathway might influence DNA methylation and, ultimately, affect gene functions. Utilizing approximately 800 breast cancer tumor tissues from a large population-based study, we investigated the relationships between dietary and genetic factors involved in the one-carbon metabolism pathway and promoter methylation of a panel of 13 breast cancer related genes. We found that CCND2, HIN1 and CHD1 were the most "dietary sensitive" genes, as methylation of their promoters was associated with intakes of at least two out of the eight dietary methyl factors examined. On the other hand, some micronutrients (i.e., B 2 and B 6) were more "epigenetically active" as their intake levels correlated with promoter methylation status in 3 out of the 13 breast cancer genes evaluated. Both positive (hypermethylation) and inverse (hypomethylation) associations with high micronutrient intake were observed. Unlike what we saw for dietary factors, we did not observe any clear patterns between one-carbon genetic polymorphisms and the promoter methylation status of the genes examined. Our results provide preliminary evidence that one carbon metabolism may have the capacity to influence the breast cancer epigenome. Given that epigenetic alterations are thought to occur early in cancer development and are potentially reversible, dietary modifications may offer promising venues for cancer intervention and prevention. PMID- 22048255 TI - Current status of primary malignant melanoma of the esophagus: clinical features, pathology, management and prognosis. AB - Primary malignant melanoma of the esophagus (PMME) is a rare disease with an extremely poor prognosis. Up to 2011, approximately 300 cases had been reported worldwide. The average age of onset is 60.5 years old, with a prevalence of males (2:1). A typical finding of PMME is a lobular or polyploid, well-circumscribed and pigmented tumor, partly covered with normal mucosa. PMME represents various colors depending on its melanin quantity and commonly coexists with intramural metastases, melanocytosis or melanoma in situ. The tumor is located from the middle to lower thoracic esophagus. The accuracy of diagnosis from biopsy is approximately 80%, because many cases are misdiagnosed as a poorly differentiated carcinoma because of the absence of melanin granules. A definite diagnosis was made by immunohistochemical examination with positive results of S100 protein, HMB45 and neuron-specific enolase. PMME has a highly metastatic potential, and the incidence of distant metastasis at the initial diagnosis is around 40-80%. A metastatic tumor from cutaneous malignant melanoma is another pigmented esophageal tumor to be considered when making the differential diagnosis for PMME. Junctional activity with melanotic cells in the adjacent epithelium and the presence of in situ melanoma and/or a satellite tumor without a previous history of cutaneous melanoma are definitive. Most of the reported patients were treated with radical esophagectomy, which is believed to be an effective approach for localized PMME. Five-year survival rates have been achieved in 37% recently, while adjuvant therapy has not been proven to increase overall survival but plays a palliative role. PMID- 22048256 TI - Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinoma. AB - BACKGROUND: Radiofrequency ablation (RFA) is a standard therapy for the treatment of hepatocellular carcinoma (HCC) with 3 or fewer tumors of up to 3 cm (early stage HCC); when RFA is unsuccessful or unfeasible, transcatheter arterial chemoembolization (TACE) has often been performed. However, little information about the outcome of TACE for early-stage HCC has been reported and it is hard to decide whether to perform additional treatment following TACE in these difficult conditions. The aim of this study was to determine the risk factors for local or intrahepatic distant recurrence after TACE in early-stage HCC. METHODS: Among 1,560 newly diagnosed HCC patients who were admitted to Okayama University Hospital, 43 patients with early-stage HCC who received only TACE in at least one nodule were enrolled in this study. We analyzed the risk factors for local and distant recurrence by the Cox proportional hazard model. RESULTS: The local recurrence rates and intrahepatic distant recurrence rates at 3 months, 6 months, and 1 year were 18.6, 33.4, and 61.8%, and 2.8, 2.8, and 34.3%, [corrected] respectively.Among 12 parameters examined as possible risk factors for recurrence, heterogeneous Lipiodol uptake (risk ratio 3.38; 95% confidence interval 1.14-10.60) and high serum des-gamma-carboxy prothrombin (DCP) (2.58; 1.03-7.14) were significantly correlated with local recurrence, and the presence of multiple tumors (10.64; 1.76-93.75) was significantly correlated with intrahepatic distant recurrence. CONCLUSIONS: Heterogeneous Lipiodol uptake, high serum DCP, and multiple tumors are risk factors for recurrence in patients with early-stage HCC who have undergone palliative TACE. PMID- 22048257 TI - Pancreatic cancer stem cell biology and its therapeutic implications. AB - Pancreatic cancer remains one of the most difficult malignancies to treat. Significant developments in our understanding of pancreatic cancer biology have occurred over the past decade. One of the key advances has been the formulation of the cancer stem cell model of tumor growth and subsequent experimental proof of pancreatic cancer stem cell existence. Cancer stem cells contribute to pancreatic tumor growth and progression and are at least partially responsible for the relative resistance of the tumor to systemic chemotherapy and radiation. Significant questions remain about how the mutational profile of the tumor, the tumor microenvironment, and normal pancreatic developmental pathways contribute to pancreatic cancer stem cell biology. Answers to these questions will likely yield new therapeutic approaches for this deadly disease. PMID- 22048258 TI - Spread of excitation and channel interaction in single- and dual-electrode cochlear implant stimulation. AB - OBJECTIVES: To determine how simultaneous dual-electrode stimulation (DES) can be optimized for the individual patient to deliver better sound quality and speech recognition. DES was compared with single-electrode stimulation (SES) with respect to the site of stimulation (X) in the cochlea, the spread of excitation (SOE), and channel interaction. Second, it was investigated whether the number of intermediate pitches created with DES can be predicted from SOE, channel interaction measures, current distribution in the cochlea, or distance of the electrode to the medial wall. DESIGN: Twelve users of the HiRes90K cochlear implant with HiFocus1J electrode were randomly selected to participate in this study. Electrode contacts were selected based on their location in the cochlea as determined by multislice computed tomography, viz. 120 degrees (basal), 240 degrees (middle), and 360 degrees (apical) from the round window. The number of intermediate pitches with simultaneous DES was assessed with a three-alternative forced choice pitch discrimination experiment. The channel interactions between two single-electrode contacts and two DES pairs were determined with a threshold detection experiment (three-alternative forced choice). The eCAP-based SOE method with fixed probe and variable masker was used to determine the location of the neurons responding to a single-electrode contact or dual-electrode contact stimulus. Furthermore, the intracochlear electrical fields were determined with the Electrical Field Imaging tool kit. RESULTS: DES was not different from SES in terms of channel interaction and SOE. The X of DES was 0.54 electrode contacts more basal compared with SES stimulation, which was not different from the predicted shift of 0.5. SOE and current distribution were significantly different for the three locations in the cochlea but showed no correlation with the number of perceivable pitches. A correlation was found between channel interaction and the number of intermediate pitches along the array within a patient, not between patients. CONCLUSION: SES and DES are equivalent with regard to SOE and channel interaction. The excitation site of DES has the predicted displacement compared with the excitation region induced by the neighboring single-electrode contact. Unfortunately, no predictor for the number of intermediate pitches was found. PMID- 22048259 TI - Population persistence under advection-diffusion in river networks. AB - An integro-differential equation on a tree graph is used to model the time evolution and spatial distribution of a population of organisms in a river network. Individual organisms become mobile at a constant rate, and disperse according to an advection-diffusion process with coefficients that are constant on the edges of the graph. Appropriate boundary conditions are imposed at the outlet and upstream nodes of the river network. The local rates of population growth/decay and that by which the organisms become mobile, are assumed constant in time and space. Imminent extinction of the population is understood as the situation whereby the zero solution to the integro-differential equation is stable. Lower and upper bounds for the eigenvalues of the dispersion operator, and related Sturm-Liouville problems are found. The analysis yields sufficient conditions for imminent extinction and/or persistence in terms of the values of water velocity, channel length, cross-sectional area and diffusivity throughout the river network. PMID- 22048260 TI - Evolutionary stability of ideal free dispersal strategies in patchy environments. AB - A central question in the study of the evolution of dispersal is what kind of dispersal strategies are evolutionarily stable. Hastings (Theor Pop Biol 24:244 251, 1983) showed that among unconditional dispersal strategies in a spatially heterogeneous but temporally constant environment, the dispersal strategy with no movement is convergent stable. McPeek and Holt's (Am Nat 140:1010-1027, 1992) work suggested that among conditional dispersal strategies in a spatially heterogeneous but temporally constant environment, an ideal free dispersal strategy, which results in the ideal free distribution for a single species at equilibrium, is evolutionarily stable. We use continuous-time and discrete-space models to determine when the dispersal strategy with no movement is evolutionarily stable and when an ideal free dispersal strategy is evolutionarily stable, both in a spatially heterogeneous but temporally constant environment. PMID- 22048261 TI - Yoga decreases insomnia in postmenopausal women: a randomized clinical trial. AB - OBJECTIVE: The practice of yoga has been proven to have positive effects on reducing insomnia. Studies have also shown its effects on reducing climacteric symptoms. To date, however, no studies that evaluate the effects of yoga on postmenopausal women with a diagnosis of insomnia in a randomized clinical trial have been conducted. The aim of this study was to evaluate the effect of yoga practice on the physical and mental health and climacteric symptoms of postmenopausal women with a diagnosis of insomnia. METHODS: Postmenopausal women not undergoing hormone therapy, who were 50 to 65 years old, who had an apnea hypopnea index less than 15, and who had a diagnosis of insomnia were randomly assigned to one of three groups, as follows: control, passive stretching, and yoga. Questionnaires were administered before and 4 months after the intervention to evaluate quality of life, anxiety and depression symptoms, climacteric symptoms, insomnia severity, daytime sleepiness, and stress. The volunteers also underwent polysomnography. The study lasted 4 months. RESULTS: There were 44 volunteers at the end of the study. When compared with the control group, the yoga group had significantly lower posttreatment scores for climacteric symptoms and insomnia severity and higher scores for quality of life and resistance phase of stress. The reduction in insomnia severity in the yoga group was significantly higher than that in the control and passive-stretching groups. CONCLUSIONS: This study showed that a specific sequence of yoga might be effective in reducing insomnia and menopausal symptoms as well as improving quality of life in postmenopausal women with insomnia. PMID- 22048262 TI - Molecular mechanics modeling of deformation and failure of super carbon nanotube networks. AB - A generalized molecular structure mechanics (MSM) model is proposed to investigate the deformation and failure behaviors of super carbon nanotubes (SCNTs) within the quasi-static approximation. The failure mechanism of the SCNTs with Y- and X-type junctions was examined by combining a failure criterion for the breakage of the carbon-carbon bonds in the CNT networks. The carbon-carbon bonds are modeled as elastic bars with equivalent stiffness and break as their elongation ratio reaches only 19%, which means that the broken carbon-carbon bonds are ineffective in terms of the Morse potential function. It is shown that the MSM method, combined with the failure criterion of the carbon-carbon bonds, is a powerful approach to simulate the deformation and failure of both Y junctions and X junctions with different chiralities and sizes. The deformation and failure modes of these junctions which involve rotation, bending and stretching of the CNT arms are predicted using the present model and the effects of various parameters of the junctions on their mechanical behaviors are discussed. PMID- 22048265 TI - Distribution of rotavirus genotypes causing nosocomial and community-acquired acute gastroenteritis at the Children's Hospital of Philadelphia in the new rotavirus vaccine era. AB - BACKGROUND: Introduction of rotavirus vaccines in the United States beginning in 2006 led to a rapid decline in the frequency of acute rotavirus gastroenteritis necessitating medical attention. We examined whether serotype replacement was occurring as a result of vaccine use. METHODS: Children with gastroenteritis presenting to CHOP have been tested for rotavirus antigen in the stool. Commencing with the 1999-2000 season, positive specimens were genotyped to establish the G (VP7) and P (VP4) type. RESULTS: In 2009-2010, 4 hospital acquired and 18 community-acquired cases of rotavirus gastroenteritis were identified at CHOP. For the third consecutive full season since the introduction of rotavirus vaccines, the proportion of annual G3 cases was higher than in the prevaccine era. Although G3 strains caused 50% of the community cases in 2009-10, the absolute number of G3 cases actually dropped from 15 in 2007-08 to 8 and 9 in the 2008-09 and 2009-10 seasons, respectively. P[8] accounted for > 90% of cases seen at CHOP in each of the last 3 seasons, including 20/22 (91%) cases during the 2009-10 season. CONCLUSIONS: Findings to date provide suggestive but still inconclusive evidence for vaccine-driven serotype replacement. Given the increased proportion of G3 cases in the new vaccine era despite the overall marked reduction in rotavirus gastroenteritis, continued surveillance is prudent. PMID- 22048266 TI - Exploratory investigation on functional significance of ETS2 and SIM2 genes in Down syndrome. AB - Trisomy of the 21{st} chromosome leads to an over dosage of several regulatory genes in Down syndrome (DS). Though allelic and genotypic combinations formed between genes are interesting, till date, this particular area has never been explored in DS. In the present investigation four SNPs in two transcription factors, Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2), located in the 21{st} chromosome were genotyped to understand their role in DS. Genomic DNA of eastern Indian probands with DS (N=132), their parents (N=209) and ethnically matched controls (N=149) was subjected to PCR-based analyses of functionally important SNPs followed by statistical analyses. ETS2 rs461155 showed high heterozygosity in DS. Significantly lower frequency of SIM2 C-G haplotype (rs2073601-rs2073416) was noticed in individuals with DS (P value =0.01669) and their fathers (P value=0.01185). Significantly lower frequency of the A-C-C-G with higher frequency of A-C-A-G haplotypes was also noticed in subjects with DS (P value =0.02089 and 0.00588 respectively). Data obtained indicate that the rs2073601 'A' allele, responsible for nonsynonymous substitution of leucine to methionine, may have some role in DS in this population. PMID- 22048267 TI - MicroRNAs, innate immunity and ventricular rupture in human myocardial infarction. AB - MicroRNAs are non-coding RNAs, functionioning as post-transcriptional regulators of gene expression. Some microRNAs have been demonstrated to play a role in regulation of innate immunity. After myocardial infarction (MI), innate immunity is activated leading to an acute inflammatory reaction. There is evidence that an intense inflammatory reaction might contribute to the development of ventricular rupture (VR) after MI. Using real-time PCR, we analysed the expression of miR 146a, miR-150, and miR-155 in autopsy samples of infarcted heart tissue from 50 patients with MI (23 with VR and 27 without VR). An altered expression of all three microRNAs was found in MI compared to the normal hearts. Comparing MI patients with VR and those without VR, we found miR-146a up-regulation, and miR 150 and miR-155 down-regulation in patients with VR. In conclusion, our study demonstrated an altered expression of miR-146a, miR-150, and miR-155 in MI compared to the normal hearts. These microRNAs are involved in regulation of the innate immunity. Differential expression of these microRNAs in MI patients with VR in comparison to those without VR provides further evidence that innate immunity resulting in an intense inflammatory reaction plays an important role in the pathogenesis of VR after MI in humans. PMID- 22048268 TI - Combined effect of ADH1B RS1229984, RS2066702 and ADH1C RS1693482/ RS698 alleles on alcoholism and chronic liver diseases. AB - The aim of this study was to analyze the combined effect of the most frequent alcohol dehydrogenase polymorphisms (Arg48His and Arg370Cys in ADH1B, Arg272Gln and Ile350Val in ADH1C) on the alcohol use habits, alcohol dependence and chronic liver diseases in Hungary. The study included men, aged 45-64 years. Altogether, 241 cases with chronic liver disease (CLD) and 666 randomly selected controls without CLD were analysed for all four polymorphisms. Associations between the polymorphisms, individually, and in combination, and excessive and problem drinking and CLD, were assessed using logistic regression. In this study we have identified a novel mutation, called ADH1B Arg370His. The ADH1C Arg272Gln and Ile350Val showed almost complete linkage. The 272Gln/35Val allele increased the risk of excessive and problem drinking in homozygous form (OR=1.582, p=0.035, CI=1.034-2.421, OR=1.780, p=0.016, CI=1.113-2.848, respectively). The joint analysis showed that when combined with the wild type ADH1C Arg272/Ile350 allele, the ADH1B 48His is protective against CLD (OR=0.368, p=0.019, CI=0.159-0.851). The results obtained in the study help not only to clarify the effects of different ADH SNPs but to better understand how these polymorphisms modify each other's effects in the development of alcoholism and related diseases. PMID- 22048269 TI - Opposite effects of GSTM1--and GSTT1: gene deletion variants on bone mineral density. AB - Oxidative stress is associated with osteoporosis. The glutathione S-transferases form the major detoxifying group of enzymes responsible for eliminating products of oxidative stress. We have therefore proposed GSTM1 and GSTT1 genes as candidates for studying the genetics of osteoporosis. The aim of the present study was to examine possible association of GSTM1 and GSTT1 gene deletion polymorphisms, alone or in combination, with bone mineral density at femoral neck (BMD_fn), lumbar spine (BMD_ls) and total hip (BMD_th) in Slovenian elderly women and men.GSTM1 and GSTT1 gene deletion polymorphisms in 712 elderly people were analyzed using the triplex PCR method for the presence of GSTM1 and GSTT1 gene segments. BMD_fn, BMD_ls and BMD_th were measured by the dual-energy X-ray absorptiometry (DEXA) method. Results were analyzed using univariate statistic model adjusted for sex, body mass index (BMI) and age. Our results showed the significant differences in BMD_th, BMD_ls and BMD_fn values (p=0.031, 0.017 and 0.023, respectively) in subgroups of GSTT1 gene deletion polymorphism. For GSTM1 gene deletion polymorphism borderline significant association was found with BMD_ls (p=0.100). Furthermore, subjects with homozygous deletion of GSTT1 gene showed higher BMD values on all measured skeletal sites and, in contrast, subjects with homozygous deletion of GSTM1 gene showed lower BMD values. Moreover, a gene-gene interaction study showed significant association of GSTM1 null and GSTT1-null polymorphisms with BMD_ls values (p=0.044). Carriers with a combination of the presence of GSTT1 gene and the homozygous absence of GSTM1 gene fragment were associated with the lower BMD values at all skeletal sites. The significant association of combination of GSTT1 gene presence and homozygous absence of GSTM1 gene with BMD was demonstrated, suggesting that it could be used, if validated in other studies, as genetic marker for low BMD. PMID- 22048270 TI - HFE gene polymorphisms and the risk for autism in Egyptian children and impact on the effect of oxidative stress. AB - BACKGROUND: Autism is among the commonest neurodevelopmental childhood disorders worldwide; its aetiology is still unknown. Iron metabolism alteration in the central nervous system is recently implicated as a risk factor for several neurodegenerative disorders. Haemochromatosis HFE gene polymorphisms (p.H63D and p.C282Y) have shown significant association with several neurological diseases. Some evidences show altered iron related proteins in serum of autistic children. The aim of this work is to conduct a preliminary pilot study for the association of HFE polymorphisms and autism. METHODS: All cases were referred from the clinic of special needs, National Research Centre, Cairo. Clinical diagnosis was based on the criteria for autistic disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). Whole genome DNA was extracted; p.H63D and p.C282Y genotyping was studied using specific sequence amplification followed by restriction enzyme digestion on a sample of autism patients (25 cases) and twenty controls. RESULTS: The p.H63D is more abundant than the C282Y among both autism and control samples. No significant association of p.H63D nor p.C282Y polymorphism and autism was revealed. CONCLUSION: We here report on the first pilot study of the possible genetic association between autism and HFE gene polymorphisms among Egyptians. Although our results do not prove the role of HFE polymorphisms as risk factors for autism, yet this does not exclude the role of iron in this prevalent disorder. Further extended studies are recommended to include other iron metabolism genes. PMID- 22048271 TI - Plasma oxidized low-density lipoprotein is an independent risk factor in young patients with coronary artery disease. AB - OBJECTIVES: Oxidized low-density lipoprotein (ox-LDL) is considered to be a key factor of initiating and accelerating atherosclerosis. The objective of this study was to investigate the role of ox-LDL in young patients with coronary artery disease (CAD). METHODS: 128 consecutive angiographically proven young CAD patients (aged ? 55 years) were enrolled, and 132 age-matched non-CAD individuals (coronary angiography normal or negative finding by coronary ultrafast CT) were set as control group. Conventional risk factors (hypertension, dyslipidemia, diabetes mellitus, obesity, smoking) were evaluated in the two groups. Ox-LDL was measured by competitive ELISA. Framingham risk score (FRS) and absolute 10-year CAD events risk were calculated for each individual. RESULTS: Male sex was more prevalent in group CAD than in control (87.5% vs. 62.1%; P< 0.01). There were significant differences in smoking history (P< 0.01) and triglyeride (TG) and ratio of apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) (both P< 0.05) but no remarkable difference in other conventional risk factors (all P> 0.05) between group CAD and control. Level of ox-LDL was significantly higher in group CAD than in control (P< 0.01). Multivariate logistic regression showed that male sex (OR, 4.54; 95%CI, 1.76-9.77), smoking quantity (OR, 2.78; 95%CI, 1.34-4.25), TG (OR, 1.42; 95%CI, 1.18-2.83), ApoB/ApoA1 (OR, 1.73; 95%CI, 1.32-4.23), and ox-LDL (OR, 2.15; 95%CI, 1.37-6.95) were independently correlated with CAD in young patients. Area under the curve (AUC) of receiver operating characteristic (ROC) curve of TG, ApoB/ApoA1, and ox-LDL was 0.831, 0.866, and 0.935, respectively (P< 0.001). CONCLUSIONS: Ox-LDL is an important independent risk factor for CAD in young patients after adjusting other risk factors such as smoking, TG, and ApoB/ApoA1. PMID- 22048272 TI - A longitudinal study of the effects of ART on plasma chemokine levels in Malaysian HIV patients. AB - OBJECTIVES: Chemokines influence the migration of leukocytes to secondary lymphoid tissue and sites of inflammation. In HIV patients, they are implicated in inflammatory complications of antiretroviral therapy (ART), notably Immune Reconstitution Disease (IRD) and Sensory Neuropathy (SN). However most chemokines have not been monitored as patients begin ART or correlated with IRD and SN. METHODS: Plasma chemokine levels were assessed longitudinally using commercial ELISAs in 69 patients treated in Kuala Lumpur, Malaysia. Plasma was available at baseline and after 6, 12, 24 and 48 weeks on ART. Chemokine genotypes were assessed using allele-specific fluorescent probes. IRD were diagnosed in 15 patients. 30 patients were screened for SN using the ACTG BPNS tool after six months on ART. SN was detected in 8 patients. RESULTS: Plasma CXCL10 levels decreased on ART compared to baseline (p=0.002-0.0001), but remain higher than healthy controls (p<= 0.0001). The decline was clearer in patients without IRD. CCL5 levels rose on ART but remained similar to controls. CCL2 levels were higher in patients than controls after week 12. Plasma chemokine levels were not affected by CD4+ T-cell counts or any genotypes tested. Several patients with SN displayed higher CCL5 levels throughout therapy compared to patients without neuropathy. Levels of other chemokines and chemokine genotypes were not associated with SN. CONCLUSIONS: Chemokines are differentially affected by ART. CXCL10 and CCL5 may influence IRD and CCL5 warrants further investigation for an effect in SN. These trends are not influenced by chemokine genotypes investigated here. PMID- 22048273 TI - Genetic polymorphism of the glutathione S-transferase M1 and T1 genes in three distinct Arab populations. AB - Deletion polymorphisms for the glutathione S-transferase (GST) gene are associated with increased risk of cancer, and are implicated in detoxifying mutagenic electrophilic compounds. GST Polymorphic variants were reported for different populations. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 null genotypes among Bahraini, Lebanese and Tunisian Arabs. GST genotyping was done by multiplex PCR-based methods. Study subjects comprised 167 Bahrainis, 141 Lebanese and 186 Tunisians unrelated healthy individuals. GSTM1 deletion homozygosity of 49.7%, 52.5% and 63.4% were recorded for Bahraini, Lebanese and Tunisians, respectively. Among Bahrainis, the prevalence of GSTT1 null homozygotes was 28.7%, while in higher rates were seen in Lebanese (37.6%) and Tunisians (37.1%). Our results indicate that there are no major differences in allelic distribution of GSTM1 and GSTT1 genes between the three Arab populations investigated except between Bahrainis and Tunisians regarding the allelic distribution of GSTM1 gene (P=0.013). Combined analysis of both genes revealed that 14.4% of Bahrainis, 16.3% of Lebanese and 21.0% of Tunisians harbor the deleted genotype of both genes. This is the first study that addresses GST gene polymorphism in Bahraini and Lebanese Arabs, and will help genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and drug effects in Arab populations. PMID- 22048274 TI - Fucose and sialic acid expressions in human seminal fibronectin and alpha{1} acid glycoprotein associated with leukocytospermia of infertile men. AB - INTRODUCTION: The aim of this study was to compare fucose and sialic acid residue expression on fibronectin and alpha{1}-acid glycoprotein in the seminal plasma of men suspected of infertility and suffering from leukocytospermia. SUBJECTS AND METHODS: Seminal ejaculates were collected from 27 leukocytospermic and 18 healthy, normozoospermic men. The relative degree of fucosylation and sialylation of fibronectin and alpha{1}-acid glycoprotein was estimated by ELISA using fucose and sialic acid specific lectins from Aleuria aurantia, Lotus tetragonolobus, and Ulex europaeus as well as Maackia amurensis and Sambucus nigra, respectively. RESULTS: Leukocytospermic seminal fibronectin, in comparison with fibronectin of normal fertile group, showed lower relative reactivity with AAL, LTA and UEA, and higher reactivity with MAA and SNA, while the AGP of the leukocytospermic group was less reactive with AAL, and the relative reactivity with LTA and MAA was significantly higher. Fibronectin and alpha{1}-acid glycoprotein reactivity with UEA and MAA showed high positive correlations. DISCUSSION: Leukocytospermia was associated with the alterations of terminal monosaccharide expression in human seminal fibronectin and alpha{1}-acid glycoprotein. The increase of sialyl-Lewis{ x} antigen in alpha{1}-acid glycoprotein can be used as a marker of genital tract inflammation manifested by leukocytospermia. PMID- 22048275 TI - Measuring population mental health and social well-being. AB - OBJECTIVES: This paper examines the relationships between indicators of positive and negative dimensions of mental health, social well-being and physical health. METHODS: The paper reports on data collected in the third National Survey of Lifestyle, Attitudes and Nutrition (SLAN 2007), a cross-sectional survey conducted with a representative sample of 10,364 Irish adults. The survey included measures of positive mental health and non-specific psychological distress from the SF-36 questionnaire, together with measures of social well being, subjective health, and selected health behaviours. RESULTS: Positive mental health is predicted by lower levels of loneliness and higher levels of social support. Better self-rated health, positive health behaviours and lower GP consultation rates are associated with higher levels of positive mental health. Lower levels of social well-being, were found to be the strongest predictors of negative mental health. CONCLUSIONS: Social well-being and health behaviours correlate with both positive and negative mental health. These findings highlight the need to endorse comprehensive approaches to population mental health promotion. The inclusion of both positive and negative mental health indicators in future population health surveys is supported by the findings. PMID- 22048276 TI - Scanning near-field IR microscopy of proteins in lipid bilayers. AB - We use infrared near-field microscopy to chemically map the morphology of biological matrices. The investigated sample is built up from surface-tethered membrane proteins (cytochrome c oxidase) reconstituted in a lipid bilayer. We have carried out infrared near-field measurements in the frequency range between 1600 and 1800 cm(-1). By simultaneously recording the topography and chemical fingerprint of the protein-tethered lipid bilayer with a lateral resolution of 80 nm * 80 nm, we were able to probe locally the chemical signature of this membrane and to provide a local map of its surface morphology. PMID- 22048277 TI - Probabilistic RNA partitioning generates transient increases in the normalized variance of RNA numbers in synchronized populations of Escherichia coli. AB - We explore the effects of probabilistic RNA partitioning during cell division on the normalized variance of RNA numbers across generations of bacterial populations. We first characterize these effects in model cell populations, where gene expression is modeled as a delayed stochastic process, as a function of the synchrony in cell division, the rate of division, and the RNA degradation rate. We further explore the additional variance that arises if the partitioning is biased. Next, in Escherichia coli cells expressing RNA tagged with MS2d-GFP, we measured the normalized variance of RNA numbers across several generations, with cell divisions synchronized by heat shock. We show that synchronized cell populations exhibit transient increases in normalized variance following cell divisions, as predicted by the model, which are not observed in unsynchronized populations. We conclude that errors in partitioning of RNA molecules generate diversity between the offspring of individual bacteria and thus constitute a form of reproductive bet-hedging. PMID- 22048278 TI - Sanofi-Cell Research Outstanding Paper Award of 2010. PMID- 22048281 TI - Cerebrospinal fluid fistulas after iliosacral screw removal in post-traumatic pseudomeningocele. AB - Sacral fractures are rare but severe injuries. They are often associated with neurological impairment and pelvic instability. We present a case of a 28-year old woman who sustained an H-type fracture of the sacrum with complete cauda equina syndrome treated with cauda equina decompression and pelvic percutaneous stabilization with an iliosacral screw. Two years after she underwent screw removal, but complained of back and nape pain after the operation. A lumbosacral MRI showed the presence of a lytic lesion involving the S1 and S2 bodies that was judged to be a pseudomeningocele leaning against the sacral screw hole and cerebrospinal fluid fistulas through this. To our knowledge, this is the first case of such a complication after sacral screw removal to be reported. PMID- 22048282 TI - Renal ischemia-reperfusion injury causes intercalated cell-specific disruption of occludin in the collecting duct. AB - Renal ischemic events open tight junctions and disrupt epithelial polarity. The purpose of this study was to examine the effects of ischemia-reperfusion (IR) injury on expression and distribution of the tight junction proteins, occludin and ZO-1, in the rat kidney. IR injury was induced by clamping both renal pedicles for 30 min and animals were killed at 6 h after the reperfusion. IR injury decreased blood bicarbonate level, but did not persistently alter pH, Na(+), K(+), or Cl(-). In control kidneys, occludin immunoreactivity was intense in the tight junctions in the thick ascending limb, distal convoluted tubule, and collecting duct, moderate in the thin limbs of the loop of Henle, and was not detected in the proximal tubule, glomerulus, and blood vessels. ZO-1 was expressed in the same sites in which occludin was expressed, and additionally was also expressed in the proximal tubule, glomerulus, and vascular endothelial cells. IR kidneys exhibited damaged renal tubular epithelial cells in both proximal tubule and collecting duct segments in the outer medulla. In the collecting duct, the response of intercalated cells and principal cells differed. Following IR injury, intercalated cells, but not principal cells, lost their normal epithelial polarity and were frequently extruded into the tubule lumen. Occludin, instead of being localized to tight junctions, was localized diffusely in the cytoplasm in intercalated cells of IR kidneys. Principal cells, in contrast, were not detectably affected and neither occludin nor ZO-1 expression were altered in response to IR injury. The normal localization of ZO-1 expression to tight junction sites in both the proximal tubule and collecting duct was altered in response to IR, and, instead, ZO-1 expression was present diffusely in the cytoplasm. IR injury did not alter detectably either occludin or ZO-1 localization to the tight junction of the thick ascending limb cells. The abundance of total occludin protein by immunoblot analysis was not changed with IR injury. These results demonstrate that renal IR injury causes tight junction disruptions in both the proximal tubule and the collecting duct, and that altered distribution of the tight junction protein, occludin, may play a critical role in the collecting duct dysfunction which IR induces. PMID- 22048283 TI - Passiflora incarnata Linneaus as an anxiolytic before spinal anesthesia. AB - PURPOSE: Patients who undergo regional anesthesia experience anxiety in the preoperative period. Passiflora incarnata Linneaus is a plant that has traditionally been used as an anxiolytic and sedative. We aimed to investigate the effect of preoperative oral administration of Passiflora incarnata Linneaus on anxiety, psychomotor functions, sedation, and hemodynamics in patients undergoing spinal anesthesia. METHODS: Under local ethics committee approval, 60 patients who were aged 25-55 years and ASAI-II and who were scheduled for spinal anesthesia were enrolled in this prospective, randomized, double-blind and placebo-controlled study. Thirty minutes before spinal anesthesia, baseline hemodynamic parameters, State-Trait Anxiety Inventory (STAI) score, sedation score, and psychomotor function test results were measured, then patients were randomly assigned to two groups: oral Passiflora incarnata Linneaus extract or placebo was given to the patients. Tests were repeated just before spinal anesthesia. Hemodynamics, sedation score, sensory-motor block and side effects were assessed during the operation. Psychomotor function tests were repeated at the end of the operation and 60 min after the operation. RESULTS: There was a statistically significant difference between the two groups for the increase in State Anxiety Inventory (STAI-S) score obtained just before spinal anesthesia when compared to the baseline. There was no statistically significant difference in psychomotor function from the baseline for either group. A significant difference was not found between the two groups in demographics, psychomotor function, sedation score, hemodynamics, and side effects. CONCLUSION: Oral preoperative administration of Passiflora incarnata Linneaus suppresses the increase in anxiety before spinal anesthesia without changing psychomotor function test results, sedation level, or hemodynamics. PMID- 22048284 TI - Recovery of psychomotor function after total intravenous anesthesia with remifentanil-propofol or fentanyl-propofol. AB - PURPOSE: Total intravenous anesthesia (TIVA) with propofol combined with remifentanil or fentanyl has commonly been used to achieve general anesthesia. The purpose of this study was to examine recovery of psychomotor function, by use of the Trieger dot test, after TIVA with remifentanil-propofol or with fentanyl propofol. METHODS: Forty patients were randomly divided into two groups of 20, to receive TIVA with either remifentanil-propofol (group R) or fentanyl-propofol (group F). Anesthesia was induced by intravenous injection of propofol. In group R, remifentanil at 0.3 MUg/kg/min was infused continuously during surgery. In group F, 3 MUg/kg fentanyl was injected as an initial dose and 1 MUg/kg fentanyl was administered intravenously every 30 min during surgery. Psychomotor function, as measured by the Trieger dot test, was evaluated before anesthesia and 30, 60, 90, 120, and 150 min after the end of TIVA. RESULTS: From assessment of the Trieger dot test, the number of dots missed in group R from 30 to 120 min after the end of TIVA was significantly lower than in group F. The maximum distance of dots missed in group R from 30 to 120 min after the end of TIVA was significantly shorter than in group F. The average distance of dots missed in group R from 30 to 120 min after the end of TIVA was significantly shorter than in group F. CONCLUSION: Recovery of psychomotor function in TIVA with remifentanil-propofol is faster than that in TIVA with fentanyl-propofol. PMID- 22048286 TI - Numerical simulation of multiple scattering by random discrete particles illuminated by Gaussian beams. AB - In this paper, we present an efficient numerical method for the simulation of multiple scattering by random discrete particles illuminated by focused Gaussian beams with arbitrary incidence. Specifically, the Davis first-order approximation in combination with rotation Euler angles is used to represent the arbitrarily incident Gaussian beams. The surface integral equations are applied to formulate the scattering problems involving multiple discrete particles with a random distribution and are numerically discretized by the method of moments. The resultant matrix equation is solved by employing the characteristic basis function method based on the use of macrobasis functions constructed according to the Foldy-Lax multiple scattering equations. Since this method only requires the solution of small-size matrix equations associated with isolated particles and it is also readily parallelized, the computational burden can be significantly relieved. Some numerical results are included to illustrate the validity of the present method and to show the scattering behaviors of random discrete particles when they are illuminated by focused Gaussian beams. PMID- 22048285 TI - Role of gabapentin in preventing fentanyl- and morphine-withdrawal-induced hyperalgesia in rats. AB - PURPOSE: This study was undertaken to examine the effect of gabapentin for preventing hyperalgesia induced by morphine and fentanyl withdrawal in rats. METHODS: To induce hyperalgesia, Sprague Dawley (SD) rats were subcutaneously injected with fentanyl four times at 15-min intervals (60 MUg/kg per injection), resulting in total dose of 240 MUg/kg over 1 h, and morphine 10 mg/kg twice daily for 7 days. The effect of gabapentin was detected with behavioral tail-flick and paw-withdrawal tests. RESULTS: Drug termination produced significant decrease in antinociception thresholds (P < 0.05 vs. saline group), indicating that the rats became sensitive to thermal stimuli. In rats that received combined treatment with fentanyl/morphine and gabapentin (25/50 mg/kg), results demonstrated that there were no significant decreases in antinociception thresholds (vs. saline group) after opioid withdrawal. Gabapentin (50 mg/kg) could also prevent morphine tolerance. The 50% effective dose (ED50) value was 12.5 mg/kg in tail-flick and 13.6 mg/kg in paw-withdrawal tests. CONCLUSIONS: The study showed that gabapentin can significantly prevented opioid-induced hyperalgesia (OIH) induced caused by fentanyl and morphine, suggesting a role for the addition of gabapentin in the perioperative period and during chronic pain treatment as an effective drug to prevent OIH. PMID- 22048287 TI - Performance enhancements to absorbance-modulation optical lithography. I. Plasmonic reflector layers. AB - The ability to improve the transmission and intensity profiles in absorbance modulation optical lithography [J. Opt. Soc. Am. A 23, 2290-2294 (2006) and Phys. Rev. Lett. 98, 043905 (2007)] through the introduction of a plasmonic metal layer is investigated. In this part of the work, a plasmonic reflector layer (PRL) is placed beneath the photoresist layer. Improvement is expected due to surface plasmons being induced on the plasmonic layer and supporting the transmission of the image deeper into the imaging layer. The introduction of the plasmonic reflector improves the depth of focus markedly, with the image confinement extended up to 60 nm but with a penalty of up to a 50% increase in the minimum full width at half-maximum of the intensity profile. The presented work demonstrates that a PRL can be a valuable tool for near-field lithography. PMID- 22048288 TI - Performance enhancements to absorbance-modulation optical lithography. II. Plasmonic superlenses. AB - The ability to improve the transmission and intensity profiles in absorbance modulation optical lithography (AMOL) [J. Opt. Soc. Am. A 23, 2290 (2006) and Phys. Rev. Lett. 98, 043905 (2007)] through the introduction of a plasmonic metal layer is investigated. In this part of the work, a plasmonic layer is placed between the absorbance-modulation layer and the photoresist layer. Transmission through this layer is possible due to the ability of thin plasmonic layers to act as near-field analogues of negative refraction materials. The superlens performance is best with a thin layer of 10-20 nm, although this causes a full width at half-maximum increase of ~50%. The introduction of the plasmonic layers allows dichroic filtering of the two wavelengths, with a difference of a factor of 10 in the transmitted intensity ratio, reducing undesirable exposure of the resist. The presented work demonstrates that a plasmonic layer can be interfaced with an AMOL system, but that further optimization and material development are needed to allow substantial performance improvements. PMID- 22048289 TI - Generalization of color-difference formulas for any illuminant and any observer by assuming perfect color constancy in a color-vision model based on the OSA-UCS system. AB - The most widely used color-difference formulas are based on color-difference data obtained under D65 illumination or similar and for a 10 degrees visual field; i.e., these formulas hold true for the CIE 1964 observer adapted to D65 illuminant. This work considers the psychometric color-vision model based on the Optical Society of America-Uniform Color Scales (OSA-UCS) system previously published by the first author [J. Opt. Soc. Am. A 21, 677 (2004); Color Res. Appl. 30, 31 (2005)] with the additional hypothesis that complete illuminant adaptation with perfect color constancy exists in the visual evaluation of color differences. In this way a computational procedure is defined for color conversion between different illuminant adaptations, which is an alternative to the current chromatic adaptation transforms. This color conversion allows the passage between different observers, e.g., CIE 1964 and CIE 1931. An application of this color conversion is here made in the color-difference evaluation for any observer and in any illuminant adaptation: these transformations convert tristimulus values related to any observer and illuminant adaptation to those related to the observer and illuminant adaptation of the definition of the color difference formulas, i.e., to the CIE 1964 observer adapted to the D65 illuminant, and then the known color-difference formulas can be applied. The adaptations to the illuminants A, C, F11, D50, Planckian and daylight at any color temperature and for CIE 1931 and CIE 1964 observers are considered as examples, and all the corresponding transformations are given for practical use. PMID- 22048290 TI - Depth-minimized, large period half-wave corrugation for linear to radial and azimuthal polarization transformation by grating-mode phase management. AB - The transformation of the polarization distribution of a laser beam from linear to radial and azimuthal by means of a subwavelength binary corrugation etched in a high-index substrate faces fabrication difficulties and an inherent contradiction preventing the achievement of both conditions of 100% transmission and of pi phase difference between polarization components. The contradiction is solved by resorting to an easily fabricable high-index corrugation on a low-index substrate where a larger period gives rise to grating-mode reflection/transmission phases that permit the fulfillment of both conditions with a depth-minimized corrugation. From the principle of the solution, a targeted numerical search gives the complete set of the corresponding shallow structures, achieving polarization rotation in a fitting analytical form versus normalized variables. PMID- 22048291 TI - Methods for computing weighting tables based on local power expansion for tristimulus values computations. AB - In this paper, two types of weighting tables are derived by applying the local power expansion method proposed by Oleari [Color Res. Appl. 25, 176 (2000)]. Both tables at two different levels consider the deconvolution of the spectrophotometric data for monochromator triangular transmittance. The first one, named zero-order weighting table, is similar to weighting table 5 of American Society for Testing and Materials (ASTM) used with the measured spectral reflectance factors (SRFs) corrected by the Stearns and Stearns formula. The second one, named second-order weighting table, is similar to weighting table 6 of ASTM and must be used with the undeconvoluted SRFs. It is hoped that the results of this paper will aid the International Commission on Illumination TC 1 71 on tristimulus integration in focusing on ongoing methods, testing, and recommendations. PMID- 22048292 TI - Orbital angular momentum of Laguerre-Gaussian beams beyond the paraxial approximation. AB - We derive a full field solution for Laguerre-Gaussian beams consistent with the Helmholtz equation using the angular spectrum method. Field components are presented as an order expansion in the ratio of the wavelength to the beam waist, f=lambda/(2piw0), which is typically small. The result is then generalized to a beam of arbitrary polarization. This result is then used to reproduce the signature angular momentum properties of Laguerre-Gaussian beams in the paraxial limit. The subsequent higher-order term is similarly obtained, which does not display a clear separation of orbital and spin angular momentum components. PMID- 22048293 TI - Solutions of large-scale electromagnetics problems involving dielectric objects with the parallel multilevel fast multipole algorithm. AB - Fast and accurate solutions of large-scale electromagnetics problems involving homogeneous dielectric objects are considered. Problems are formulated with the electric and magnetic current combined-field integral equation and discretized with the Rao-Wilton-Glisson functions. Solutions are performed iteratively by using the multilevel fast multipole algorithm (MLFMA). For the solution of large scale problems discretized with millions of unknowns, MLFMA is parallelized on distributed-memory architectures using a rigorous technique, namely, the hierarchical partitioning strategy. Efficiency and accuracy of the developed implementation are demonstrated on very large problems involving as many as 100 million unknowns. PMID- 22048294 TI - Fast convergence with spectral volume integral equation for crossed block-shaped gratings with improved material interface conditions. AB - For block-shaped dielectric gratings with two-dimensional periodicity, a spectral domain volume integral equation is derived in which explicit Fourier factorization rules are employed. The Fourier factorization rules are derived from a projection-operator framework and enhance the numerical accuracy of the method, while maintaining a low computational complexity of O(NlogN) or better and a low memory demand of O(N). PMID- 22048295 TI - Three-dimensional polarization states of monochromatic light fields. AB - The 3*1 generalized Jones vectors (GJVs) [E(x) E(y) E(z)](t) (t indicates the transpose) that describe the linear, circular, and elliptical polarization states of an arbitrary three-dimensional (3-D) monochromatic light field are determined in terms of the geometrical parameters of the 3-D vibration of the time-harmonic electric field. In three dimensions, there are as many distinct linear polarization states as there are points on the surface of a hemisphere, and the number of distinct 3-D circular polarization states equals that of all two dimensional (2-D) polarization states on the Poincare sphere, of which only two are circular states. The subset of 3-D polarization states that results from the superposition of three mutually orthogonal x, y, and z field components of equal amplitude is considered as a function of their relative phases. Interesting contours of equal ellipticity and equal inclination of the normal to the polarization ellipse with respect to the x axis are obtained in 2-D phase space. Finally, the 3*3 generalized Jones calculus, in which elastic scattering (e.g., by a nano-object in the near field) is characterized by the 3-D linear transformation E(s)=T E(i), is briefly introduced. In such a matrix transformation, E(i) and E(s) are the 3*1 GJVs of the incident and scattered waves and T is the 3*3 generalized Jones matrix of the scatterer at a given frequency and for given directions of incidence and scattering. PMID- 22048296 TI - Highlight detection and removal from spectral image. AB - We present a constrained spectral unmixing method to remove highlight from a single spectral image. In the constrained spectral unmixing method, the constraints have been imposed so that all the fractions of diffuse and highlight reflection sum up to 1 and are positive. As a result, the spectra of the diffuse image are always positive. The spectral power distribution (SPD) of the light source has been used as the pure highlight spectrum. The pure diffuse spectrum of the measured spectrum has been chosen from the set of diffuse spectra. The pure diffuse spectrum has a minimum angle among the angles calculated between spectra from a set of diffuse spectra and the measured spectrum projected onto the subspace orthogonal to the SPD of the light source. The set of diffuse spectra has been collected by an automated target generation program from the diffuse part in the image. Constrained energy minimization in a finite impulse response linear filter has been used to detect the highlight and diffuse parts in the image. Results by constrained spectral unmixing have been compared with results by the orthogonal subspace projection (OSP) method [Proceedings of International Conference on Pattern Recognition (2006), pp. 812-815] and probabilistic principal component analysis (PPCA) [Proceedings of the 4th WSEAS International Conference on Signal Processing, Robotics and Automation (2005), paper 15]. Constrained spectral unmixing outperforms OSP and PPCA in the visual assessment of the diffuse results. The highlight removal method by constrained spectral unmixing is suitable for spectral images. PMID- 22048297 TI - Effective medium theory for random media composed of two-layered spheres. AB - We study the effective index of random media composed of two-layered spheres by using the energy-density coherent potential approximation method. As expected from the Ewald-Oseen extinction theorem, in the long-wavelength limit, the optical properties of a random medium composed of two-layered spheres are identical to those of a random medium composed of the corresponding pure spheres, while in the Mie-scattering region, the single-scattering resonances lead to an overall shift of the effective refractive index with the modified volume fraction. PMID- 22048298 TI - Fast computation of an optimal controller for large-scale adaptive optics. AB - The linear quadratic Gaussian regulator provides the minimum-variance control solution for a linear time-invariant system. For adaptive optics (AO) applications, under the hypothesis of a deformable mirror with instantaneous response, such a controller boils down to a minimum-variance phase estimator (a Kalman filter) and a projection onto the mirror space. The Kalman filter gain can be computed by solving an algebraic Riccati matrix equation, whose computational complexity grows very quickly with the size of the telescope aperture. This "curse of dimensionality" makes the standard solvers for Riccati equations very slow in the case of extremely large telescopes. In this article, we propose a way of computing the Kalman gain for AO systems by means of an approximation that considers the turbulence phase screen as the cropped version of an infinite-size screen. We demonstrate the advantages of the methods for both off- and on-line computational time, and we evaluate its performance for classical AO as well as for wide-field tomographic AO with multiple natural guide stars. Simulation results are reported. PMID- 22048299 TI - Full-complex amplitude modulation with binary spatial light modulators. AB - Imperfections and nonrobust behavior of practical multilevel spatial light modulators (SLMs) degrade the performance of many proposed full-complex amplitude modulation schemes. We consider the use of more robust binary SLMs for this purpose. We propose a generic method, by which, out of K binary (or 1 bit) SLMs of size M*N, we effectively create a new 2(K)-level (or K bit) SLM of size M*N. The method is a generalization of the well-known concepts of bit plane representation and decomposition for ordinary gray scale digital images and relies on forming a properly weighted superposition of binary SLMs. When K is sufficiently large, the effective SLM can be regarded as a full-complex one. Our method is as efficient as possible from an information theoretical perspective. A 4f system is discussed as a possible optical implementation. This 4f system also provides a means for eliminating the undesirable higher diffraction orders. The components of the 4f system can easily be customized for different production technologies. PMID- 22048300 TI - Ultrasound-modulated optical tomography: recovery of amplitude of vibration in the insonified region from boundary measurement of light correlation. AB - We address a certain inverse problem in ultrasound-modulated optical tomography: the recovery of the amplitude of vibration of scatterers [p(r)] in the ultrasound focal volume in a diffusive object from boundary measurement of the modulation depth (M) of the amplitude autocorrelation of light [phi(r,tau)] traversing through it. Since M is dependent on the stiffness of the material, this is the precursor to elasticity imaging. The propagation of phi(r,tau) is described by a diffusion equation from which we have derived a nonlinear perturbation equation connecting p(r) and refractive index modulation [Deltan(r)] in the region of interest to M measured on the boundary. The nonlinear perturbation equation and its approximate linear counterpart are solved for the recovery of p(r). The numerical results reveal regions of different stiffness, proving that the present method recovers p(r) with reasonable quantitative accuracy and spatial resolution. PMID- 22048301 TI - Off-plane anastigmatic imaging in Offner spectrometers. AB - In this paper, the imaging performance of an Offner concentric imaging spectrometer is analyzed when the spectrometer entrance slit is disposed arbitrarily on the plane that is parallel to the grating grooves and contains the common center of curvature. Astigmatism-corrected designs are obtained for off plane incidence on the grating if one point on the slit is located on the Rowland circle of the primary mirror. In this case, the combined system of primary mirror plus diffraction grating provides two astigmatic line images oriented parallel and orthogonal to the plane of diffraction, with the former located on the same plane as the slit. Consequently, these images can be brought to a single focus on this plane by the tertiary mirror if its radius of curvature is chosen properly. In addition, coma aberration is simultaneously removed. These results can be applied to the design of two-mirror or three-mirror spectrometers, generalizing the concept of the best imaging circle and providing solutions to get anastigmatic imaging for two object points and two wavelengths. PMID- 22048302 TI - Self-consistent optical constants of SiC thin films. AB - The optical constants of ion-beam-sputtered SiC films have been measured by ellipsometry in the 190 to 950 nm range. The set of data has been extended both toward shorter and longer wavelengths with data in the literature, along with inter- and extrapolations, in order to obtain a self-consistent set of data by means of Kramers-Kronig analysis. All data correspond to films that were deposited by sputtering on nonheated substrates, and hence they are expected to be amorphous. A bandgap of 1.9 eV for the films was fitted from the obtained optical constants. A good global accuracy of the data was estimated through the use of various sum rules. The consistent dataset includes the visible to the extreme ultraviolet (EUV); this large spectrum of characterization will enable the design of multilayer coatings that combine a high reflectance in parts of the EUV with desired performance at a secondary range, such as the visible. To our knowledge, this paper provides the first compilation of the optical constants of amorphous SiC films. PMID- 22048303 TI - Resolution improvement by single-exposure superresolved interferometric microscopy with a monochrome sensor. AB - Single-exposure superresolved interferometric microscopy (SESRIM) by RGB multiplexing has recently been proposed as a way to achieve one-dimensional superresolved imaging in digital holographic microscopy by a single-color CCD snapshot [Opt. Lett. 36, 885 (2011)]. Here we provide the mathematical basis for the operating principle of SESRIM, while we also present a different experimental configuration where the color CCD camera is replaced by a monochrome (B&W) CCD camera. To maintain the single-exposure working principle, the object field of view (FOV) is restricted and the holographic recording is based on image-plane wavelength-dispersion spatial multiplexing to separately record the three bandpass images. Moreover, a two-dimensional extension is presented by considering two options: time multiplexing and selective angular multiplexing. And as an additional implementation, the FOV restriction is eliminated by varying the angle between the three reference beams in the interferometric recording. Experimental results are reported for all of the above-mentioned cases. PMID- 22048304 TI - Integral imaging using phase-only LCoS spatial light modulators as Fresnel lenslet arrays. AB - We present a digital integral imaging system. A Fresnel lenslet array pattern is written on a phase-only LCoS spatial light modulator device (SLM) to replace the regular analog lenslet array in a conventional integral imaging system. We theoretically analyze the capture part of the proposed system based on Fresnel wave propagation formulation. Because of pixelation and quantization of the lenslet array pattern, higher diffraction orders and multiple focal points emerge. Because of the multiple focal planes introduced by the discrete lenslets, multiple image planes are observed. The use of discrete lenslet arrays also causes some other artifacts on the recorded elemental images. The results reduce to those available in the literature when the effects introduced by the discrete nature of the lenslets are omitted. We performed simulations of the capture part. It is possible to obtain the elemental images with an acceptable visual quality. We also constructed an optical integral imaging system with both capture and display parts using the proposed discrete Fresnel lenslet array written on a SLM. Optical results when self-luminous objects, such as an LED array, are used indicate that the proposed system yields satisfactory results. PMID- 22048305 TI - Electromagnetic plane wave scattering by arbitrarily oriented elliptical dielectric cylinders. AB - The electromagnetic scattering by an arbitrarily oriented elliptical cylinder having different constitutive parameters than those of the background medium is treated in this work. The separation of variables method is used to solve this problem, but, due to the oblique incidence of the source fields, hybrid waves for the scattered and induced fields are generated, thus making the formulation complicated. Moreover, because of the different wavenumbers between the scatterer and the background medium, the orthogonality relations for Mathieu functions do not hold, leading to more complicated systems, compared to those of normal incidence, which should be solved in order to obtain the solution for the scattered or induced fields. The validation of the results reveals the high accuracy of the implementation, even for electrically large scatterers. Both polarizations are considered and numerical results are given for various values of the parameters. The method is exact and can be used for reference as an alternative validation for future methods involving scattering problems. PMID- 22048306 TI - Spectral color constancy using a maximum entropy approach. AB - This paper proposes a solution to the spectral color constancy problem. The method is based on a statistical model for the surface reflectance spectrum and applies a maximum entropy constraint. Unlike prior methods based on linear models, the solution process does not require a set of basis functions to be defined, nor does it require a database of spectra to be specified in advance. Experiments on simulated and real data show that spectral estimation using the maximum entropy approach is feasible and performs similarly to existing spectral methods in spite of the lower level of a priori information required. PMID- 22048307 TI - Code aperture optimization for spectrally agile compressive imaging. AB - Coded aperture snapshot spectral imaging (CASSI) provides a mechanism for capturing a 3D spectral cube with a single shot 2D measurement. In many applications selective spectral imaging is sought since relevant information often lies within a subset of spectral bands. Capturing and reconstructing all the spectral bands in the observed image cube, to then throw away a large portion of this data, is inefficient. To this end, this paper extends the concept of CASSI to a system admitting multiple shot measurements, which leads not only to higher quality of reconstruction but also to spectrally selective imaging when the sequence of code aperture patterns is optimized. The aperture code optimization problem is shown to be analogous to the optimization of a constrained multichannel filter bank. The optimal code apertures allow the decomposition of the CASSI measurement into several subsets, each having information from only a few selected spectral bands. The rich theory of compressive sensing is used to effectively reconstruct the spectral bands of interest from the measurements. A number of simulations are developed to illustrate the spectral imaging characteristics attained by optimal aperture codes. PMID- 22048308 TI - Spectral bidirectional reflectance distribution function measurements on well defined textured surfaces: direct observation of shadowing, masking, inter reflection, and transparency effects. AB - We present results for the bidirectional reflectance distribution function (BRDF) for samples of uniform rectangular and triangular grooves constructed from polydimethylsilicone replicas. The measurements are performed with the detector in the plane of incidence, but with varying groove orientations with respect to that plane. The samples are opaque in some cases and semitransparent in others. By measuring the BRDF for colored samples over a wide spectral range, we explicitly probe the effect of sample albedo, which is important for inter reflections. For the opaque samples, we compare the results with exact theoretical results either taken from the literature (for the triangular geometry) or worked out here (for the rectangular geometry). For both geometries, we also extend the theoretical results to finite length grooves. There is generally very good agreement between theory and the experiment. Shadowing, masking, and inter-reflection are clearly observed, as well as effects that may be due to polarization and asperity scattering. For semitransparent samples, we observe the effect of increasing transparency on the BRDF. PMID- 22048309 TI - Direct electrical junction formation of highly vertical aligned zinc oxide nanorods. AB - A two dimensionally assembled monolayer of hexagonal convexo-convex beta-cobalt hydroxide nanoplates as a self-disposable sacrificial epi-template leads to a highly vertical alignment of zinc oxide nanorods array having a good electrical contact with metal or semiconductor layer on a substrate in a hydrothermal process. PMID- 22048310 TI - Adherens junction protein nectin-4 is the epithelial receptor for measles virus. AB - Measles virus is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. Although it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to infect initially macrophages and dendritic cells of the airways using signalling lymphocytic activation molecule family member 1 (SLAMF1; also called CD150) as a receptor. These cells then cross the respiratory epithelium and transport the infection to lymphatic organs where measles virus replicates vigorously. How and where the virus crosses back into the airways has remained unknown. On the basis of functional analyses of surface proteins preferentially expressed on virus-permissive human epithelial cell lines, here we identify nectin-4 (ref. 8; also called poliovirus-receptor-like-4 (PVRL4)) as a candidate host exit receptor. This adherens junction protein of the immunoglobulin superfamily interacts with the viral attachment protein with high affinity through its membrane-distal domain. Nectin-4 sustains measles virus entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally. It is downregulated in infected epithelial cells, including those of macaque tracheae. Although other viruses use receptors to enter hosts or transit through their epithelial barriers, we suggest that measles virus targets nectin-4 to emerge in the airways. Nectin-4 is a cellular marker of several types of cancer, which has implications for ongoing measles-virus-based clinical trials of oncolysis. PMID- 22048311 TI - Early dispersal of modern humans in Europe and implications for Neanderthal behaviour. AB - The appearance of anatomically modern humans in Europe and the nature of the transition from the Middle to Upper Palaeolithic are matters of intense debate. Most researchers accept that before the arrival of anatomically modern humans, Neanderthals had adopted several 'transitional' technocomplexes. Two of these, the Uluzzian of southern Europe and the Chatelperronian of western Europe, are key to current interpretations regarding the timing of arrival of anatomically modern humans in the region and their potential interaction with Neanderthal populations. They are also central to current debates regarding the cognitive abilities of Neanderthals and the reasons behind their extinction. However, the actual fossil evidence associated with these assemblages is scant and fragmentary, and recent work has questioned the attribution of the Chatelperronian to Neanderthals on the basis of taphonomic mixing and lithic analysis. Here we reanalyse the deciduous molars from the Grotta del Cavallo (southern Italy), associated with the Uluzzian and originally classified as Neanderthal. Using two independent morphometric methods based on microtomographic data, we show that the Cavallo specimens can be attributed to anatomically modern humans. The secure context of the teeth provides crucial evidence that the makers of the Uluzzian technocomplex were therefore not Neanderthals. In addition, new chronometric data for the Uluzzian layers of Grotta del Cavallo obtained from associated shell beads and included within a Bayesian age model show that the teeth must date to ~45,000-43,000 calendar years before present. The Cavallo human remains are therefore the oldest known European anatomically modern humans, confirming a rapid dispersal of modern humans across the continent before the Aurignacian and the disappearance of Neanderthals. PMID- 22048312 TI - Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. AB - Advanced age is the main risk factor for most chronic diseases and functional deficits in humans, but the fundamental mechanisms that drive ageing remain largely unknown, impeding the development of interventions that might delay or prevent age-related disorders and maximize healthy lifespan. Cellular senescence, which halts the proliferation of damaged or dysfunctional cells, is an important mechanism to constrain the malignant progression of tumour cells. Senescent cells accumulate in various tissues and organs with ageing and have been hypothesized to disrupt tissue structure and function because of the components they secrete. However, whether senescent cells are causally implicated in age-related dysfunction and whether their removal is beneficial has remained unknown. To address these fundamental questions, we made use of a biomarker for senescence, p16(Ink4a), to design a novel transgene, INK-ATTAC, for inducible elimination of p16(Ink4a)-positive senescent cells upon administration of a drug. Here we show that in the BubR1 progeroid mouse background, INK-ATTAC removes p16(Ink4a) positive senescent cells upon drug treatment. In tissues--such as adipose tissue, skeletal muscle and eye--in which p16(Ink4a) contributes to the acquisition of age-related pathologies, life-long removal of p16(Ink4a)-expressing cells delayed onset of these phenotypes. Furthermore, late-life clearance attenuated progression of already established age-related disorders. These data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan. PMID- 22048314 TI - The earliest evidence for anatomically modern humans in northwestern Europe. AB - The earliest anatomically modern humans in Europe are thought to have appeared around 43,000-42,000 calendar years before present (43-42 kyr cal BP), by association with Aurignacian sites and lithic assemblages assumed to have been made by modern humans rather than by Neanderthals. However, the actual physical evidence for modern humans is extremely rare, and direct dates reach no farther back than about 41-39 kyr cal BP, leaving a gap. Here we show, using stratigraphic, chronological and archaeological data, that a fragment of human maxilla from the Kent's Cavern site, UK, dates to the earlier period. The maxilla (KC4), which was excavated in 1927, was initially diagnosed as Upper Palaeolithic modern human. In 1989, it was directly radiocarbon dated by accelerator mass spectrometry to 36.4-34.7 kyr cal BP. Using a Bayesian analysis of new ultrafiltered bone collagen dates in an ordered stratigraphic sequence at the site, we show that this date is a considerable underestimate. Instead, KC4 dates to 44.2-41.5 kyr cal BP. This makes it older than any other equivalently dated modern human specimen and directly contemporary with the latest European Neanderthals, thus making its taxonomic attribution crucial. We also show that in 13 dental traits KC4 possesses modern human rather than Neanderthal characteristics; three other traits show Neanderthal affinities and a further seven are ambiguous. KC4 therefore represents the oldest known anatomically modern human fossil in northwestern Europe, fills a key gap between the earliest dated Aurignacian remains and the earliest human skeletal remains, and demonstrates the wide and rapid dispersal of early modern humans across Europe more than 40 kyr ago. PMID- 22048313 TI - Species-specific responses of Late Quaternary megafauna to climate and humans. AB - Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change. PMID- 22048315 TI - Structure and function of the AAA+ protein CbbX, a red-type Rubisco activase. AB - Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyses the fixation of atmospheric CO(2) in photosynthesis, but tends to form inactive complexes with its substrate ribulose 1,5-bisphosphate (RuBP). In plants, Rubisco is reactivated by the AAA(+) (ATPases associated with various cellular activities) protein Rubisco activase (Rca), but no such protein is known for the Rubisco of red algae. Here we identify the protein CbbX as an activase of red-type Rubisco. The 3.0-A crystal structure of unassembled CbbX from Rhodobacter sphaeroides revealed an AAA(+) protein architecture. Electron microscopy and biochemical analysis showed that ATP and RuBP must bind to convert CbbX into functionally active, hexameric rings. The CbbX ATPase is strongly stimulated by RuBP and Rubisco. Mutational analysis suggests that CbbX functions by transiently pulling the carboxy-terminal peptide of the Rubisco large subunit into the hexamer pore, resulting in the release of the inhibitory RuBP. Understanding Rubisco activation may facilitate efforts to improve CO(2) uptake and biomass production by photosynthetic organisms. PMID- 22048317 TI - Diagnostic imaging of an Achilles tendon rupture. AB - The patient was a 45-year-old man who was referred to a physical therapist with a chief complaint of posterior right ankle pain for the past 2 weeks. The physical therapist requested radiographs, which demonstrated obliteration of Kager's fat pad, a finding highly suspicious for an Achilles tendon rupture. Based upon history, physical examination, and radiographic findings, the physical therapist ordered magnetic resonance imaging which confirmed the diagnosis of Achilles tendon rupture. PMID- 22048316 TI - Infrared diffuse interstellar bands in the Galactic Centre region. AB - The spectrum of any star viewed through a sufficient quantity of diffuse interstellar material reveals a number of absorption features collectively called 'diffuse interstellar bands' (DIBs). The first DIBs were reported about 90 years ago, and currently well over 500 are known. None of them has been convincingly identified with any specific element or molecule, although recent studies suggest that the DIB carriers are polyatomic molecules containing carbon. Most of the DIBs currently known are at visible and very near-infrared wavelengths, with only two previously known at wavelengths beyond one micrometre (10,000 angstroms), the longer of which is at 1.318 micrometres (ref. 6). Here we report 13 diffuse interstellar bands in the 1.5-1.8 micrometre interval on high-extinction sightlines towards stars in the Galactic Centre. We argue that they originate almost entirely in the Galactic Centre region, a considerably warmer and harsher environment than where DIBs have been observed previously. The relative strengths of these DIBs towards the Galactic Centre and the Cygnus OB2 diffuse cloud are consistent with their strengths scaling mainly with the extinction by diffuse material. PMID- 22048318 TI - Neutral coordination polymers based on a metal-mono(dithiolene) complex: synthesis, crystal structure and supramolecular chemistry of [Zn(dmit)(4,4' bpy)]n, [Zn(dmit)(4,4'-bpe)]n and [Zn(dmit)(bix)]n (4,4'-bpy = 4,4'-bipyridine, 4,4'-bpe = trans-1,2-bis(4-pyridyl)ethene, bix = 1,4-bis(imidazole-1-ylmethyl) benzene. AB - This article describes a unique synthetic route that enables a neutral mono(dithiolene)metal unit, {Zn(dmit)}, to link with three different organic molecules, resulting in the isolation of a new class of neutral coordination polymers. The species {Zn(dmit)} coordinates with 4,4'-bipyridine (4,4'-bpy), trans-1,2-bis(4-pyridyl)ethene (4,4'-bpe) and 1,4-bis(imidazole-1-ylmethyl) benzene (bix) as linkers giving rise to the formation of coordination polymers [Zn(dmit)(4,4'-bpy)](n) (1), [Zn(dmit)(4,4'-bpe)](n) (2) and [Zn(dmit)(bix)](n) (3) respectively. Compounds 1-3 were characterized by elemental analyses, IR, diffuse reflectance and single crystal X-ray diffraction studies. Compounds 1 and 3 crystallize in the monoclinic space group P2(1)/n, whereby compound 2 crystallizes in triclinic space group P1[combining macron]. In the present study, we chose three linkers 4,4'-bpy, 4,4'-bpe and bix (see , respectively, for their structural drawings), that differ in terms of their molecular dimensions. The crystal structures of compounds 1-3 are described here in terms of their supramolecular diversities that include pi-pi interactions, not only among aromatic stacking (compounds 1 and 3), but also between an aromatic ring and an ethylenic double bond (compound 2). The electronic absorption spectroscopy of compounds 1-3 support these intermolecular pi-pi interactions. PMID- 22048319 TI - Categorizing natural objects: a comparison of the visual and the haptic modalities. AB - Although the hands are the most important tool for humans to manipulate objects, only little is known about haptic processing of natural objects. Here, we selected a unique set of natural objects, namely seashells, which vary along a variety of object features, while others are shared across all stimuli. To correctly interact with objects, they have to be identified or categorized. For both processes, measuring similarities between objects is crucial. Our goal is to better understand the haptic similarity percept by comparing it to the visual similarity percept. First, direct similarity measures were analyzed using multidimensional scaling techniques to visualize the perceptual spaces of both modalities. We find that the visual and the haptic modality form almost identical perceptual spaces. Next, we performed three different categorization tasks. All tasks exhibit a highly accurate processing of complex shapes of the haptic modality. Moreover, we find that objects grouped into the same category form regions within the perceptual space. Hence, in both modalities, perceived similarity constitutes the basis for categorizing objects. Moreover, both modalities focus on shape to form categories. Taken together, our results lead to the assumption that the same cognitive processes link haptic and visual similarity perception and the resulting categorization behavior. PMID- 22048320 TI - The relationship between periodic dinucleotides and the nucleosomal DNA deformation revealed by normal mode analysis. AB - Nucleosomes, which contain DNA and proteins, are the basic unit of eukaryotic chromatins. Polymers such as DNA and proteins are dynamic, and their conformational changes can lead to functional changes. Periodic dinucleotide patterns exist in nucleosomal DNA chains and play an important role in the nucleosome structure. In this paper, we use normal mode analysis to detect significant structural deformations of nucleosomal DNA and investigate the relationship between periodic dinucleotides and DNA motions. We have found that periodic dinucleotides are usually located at the peaks or valleys of DNA and protein motions, revealing that they dominate the nucleosome dynamics. Also, a specific dinucleotide pattern CA/TG appears most frequently. PMID- 22048321 TI - EMR development... Always be prepared. PMID- 22048322 TI - Family connectedness moderates the association between living alone and suicide ideation in a clinical sample of adults 50 years and older. AB - OBJECTIVE: To investigate whether living alone is significantly associated with expression of suicide ideation among mood-disordered mental health patients and whether degree of family connectedness moderates the association between living alone and expression of suicide ideation. DESIGN: Cross-sectional survey design. SETTING: Inpatient and outpatient mental health services in Rochester, New York. PARTICIPANTS: A total of 130-mood-disordered inpatients and outpatients 50 years and older. MEASUREMENTS: Patients completed a demographics form, an interviewer rated measure of current suicide ideation (Scale for Suicide Ideation), and a self-report measure of family connectedness derived from the Reasons for Living Scale-Older Adult version. RESULTS: Patients who reported greater family connectedness were significantly less likely to report suicide ideation; this protective effect was strongest for those living with others (Wald chi(2)[df = 1] = 3.987, p = 0.046, OR = 0.905; 95% CI = 0.821-0.998). A significant main effect of family connectedness on suicide ideation suggested that having a stronger connection to family members decreased the likelihood of reporting suicide ideation (Wald chi(2)[df = 1] = 9.730, p = 0.002, OR = 0.852; 95% CI = 0.771 0.942). CONCLUSIONS: These results suggest potential value in assessing the quality of interpersonal relationships when conducting a suicide risk assessment among depressed middle-aged and older adults. PMID- 22048323 TI - Relationships between behavioral syndromes and cognitive domains in Alzheimer disease: the impact of mood and psychosis. AB - OBJECTIVES: Behavioral disturbances occur in nearly all Alzheimer disease (AD) patients together with an array of cognitive impairments. Prior investigations have failed to demonstrate specific associations between them, suggesting an independent, rather than shared, pathophysiology. The objective of this study was to reexamine this issue using an extensive cognitive battery together with a sensitive neurobehavioral and functional rating scale to correlate behavioral syndromes and cognitive domains across the spectrum of impairment in dementia. DESIGN: Cross-sectional study of comprehensive cognitive and behavioral ratings in subjects with AD and mild cognitive impairment. SETTING: Memory disorders research center. PARTICIPANTS: Fifty subjects with AD and 26 subjects with mild cognitive impairment; and their caregivers. MEASUREMENTS: Cognitive rating scales administered included the Mini-Mental State Examination; the Modified Mini-Mental State Examination; the Boston Naming Test; the Benton Visual Retention Test; the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychology Assessment; the Controlled Oral Word Test; the Wechsler Memory Scale logical memory I and logical memory II task; the Wechsler Memory Scale-Revised digit span; the Wechsler Adult Intelligence Scale-Revised digit symbol task; and the Clock Drawing Task together with the Clinical Dementia Rating Scale and the Neuropsychiatric Inventory. RESULTS: Stepwise regression of cognitive domains with symptom domains revealed significant associations of mood with impaired executive function/speed of processing (Deltar = 0.22); impaired working memory (Deltar = 0.05); impaired visual memory (Deltar = 0.07); and worsened Clinical Dementia Rating Scale (Deltar = 0.08). Psychosis was significantly associated with impaired working memory (Deltar = 0.13). CONCLUSIONS: Mood symptoms appear to impact diverse cognitive realms and to compromise functional performance. Among neuropsychological indices, the unique relationship between working memory and psychosis suggests a possible common underlying neurobiology. PMID- 22048324 TI - L-Arginine but not L-glutamine likely increases exogenous carbohydrate oxidation during endurance exercise. AB - The addition of L-arginine or L-glutamine to glucose-electrolyte solutions can increase intestinal water, glucose, and sodium absorption in rats and humans. We evaluated the utility of L-arginine and L-glutamine in energy-rehydration beverages through assessment of exogenous glucose oxidation and perceptions of exertion and gastrointestinal distress during endurance exercise. Eight cyclists rode 150 min at 50% of peak power on four occasions while ingesting solutions at a rate of 150 mL 15 min(-1) that contained (13)C-enriched glucose (266 mmol L( 1)) and sodium citrate ([Na(+)] 60 mmol L(-1)), and either: 4.25 mmol L(-1) L arginine or 45 mmol L(-1) L-glutamine, and as controls glucose only or no glucose. Relative to glucose only, L-arginine invoked a likely 12% increase in exogenous glucose oxidation (90% confidence limits: +/- 8%); however, the effect of L-glutamine was possibly trivial (4.5 +/- 7.3%). L-Arginine also led to very likely small reductions in endogenous fat oxidation rate relative to glucose (12 +/- 4%) and L-glutamine (14 +/- 4%), and relative to no glucose, likely reductions in exercise oxygen consumption (2.6 +/- 1.5%) and plasma lactate concentration (0.20 +/- 0.16 mmol L(-1)). Effects on endogenous and total carbohydrate oxidation were inconsequential. Compared with glucose only, L arginine and L-glutamine caused likely small-moderate effect size increases in perceptions of stomach fullness, abdominal cramp, exertion, and muscle tiredness during exercise. Addition of L-arginine to a glucose and electrolyte solution increases the oxidation of exogenous glucose and decreases the oxygen cost of exercise, although the mechanisms responsible and impact on endurance performance require further investigation. However, L-arginine also increases subjective feelings of gastrointestinal distress, which may attenuate its other benefits. PMID- 22048325 TI - Current developments in transcatheter aortic valve implantation techniques. AB - Transcatheter aortic valve implantation (TAVI) has become a viable treatment option in high-risk patients with symptomatic aortic stenosis. The widespread uses of TAVI procedures in recent years and the steadily growing evolution of numerous new catheter-based devices have led to a remarkable shift in the treatment of this patients group towards TAVI procedures. Several developments have now overcome most of the initial problems with the early devices and have been quickly implemented in clinical routine. Nevertheless, several current TAVI systems have shown a number of limitations and disadvantages relating to valve design, the occurrence of paravalvular leakages, valve positioning and deployment, the occurrence of thromboembolic events during the procedure, as well as vascular or conduction complications. As a result, all current efforts in further development focus primarily on the following issues: (1) the further miniaturization of catheter devices and sheaths not only to facilitate transarterial but also transapical access; (2) the development of a broad variety of valve sizes to cover all aortic annulus sizes; (3) the development of retrievable, repositionable and removable systems; (4) the development or modification of stent design to prevent or reduce paravalvular leakages; (5) the implementation of modern imaging and navigation tools; (6) and finally, the initial development of prophylactic devices to prevent thromboembolic events. The present article provides a review of current developments in the field of TAVI. PMID- 22048326 TI - [Angioscopy: a new intraoperative diagnostic and interventional tool for thoracic aortic treatment]. AB - In complex thoracic aortic disease endovascular techniques and the use of hybrid stent grafts enables a combination therapy of the aortic arch and the descending aorta through a median sternotomy. This emphasizes the importance of intraoperative visualization of the descending aorta and its pathologies. Intraoperative angioscopy is a new diagnostic method for the assessment of distal aortic disease and assists in therapeutic decision-making and navigation of endovascular techniques in the descending aorta. This study presents the angioscopic results of 62 patients (mean age 60+/-12 years, 73% male, 54 aortic dissections, eight aortic aneurysms) during surgery of the thoracic aorta. Visualization of the extent of pathology along the downstream aorta was feasible in all patients. The implantation of a hybrid stent graft prosthesis was assisted by angioscopy in 34 patients and endovascular balloon dilatation of the stent graft was navigated by angioscopy in 11 patients. Angioscopy has become an indispensable tool in the intraoperative treatment of complex thoracic aortic disease in our clinic, particularly in the navigation of endovascular interventions in the distal thoracic aorta through the aortic arch. PMID- 22048327 TI - [What is new in heart surgery?]. PMID- 22048328 TI - [Sleep apnoea syndrome in the rehabilitation setting]. AB - Sleep-related breathing disorders are a common finding in patients undergoing cardiological rehabilitation. Sleep apnoea is recognized as a major risk factor for cardiovascular disorders. The diagnosis of sleep-related breathing disorders begins with taking a thorough sleep medicine-related patient history and answering dedicated questionnaires. The second step involves portable monitoring to assess oxygen saturation, heart rate, respiratory flow and effort. Portable monitoring is able to detect the severity of the breathing disorder and forms the basis on which to refer the patient for further sleep laboratory diagnosis or, in the case of positive results, to initiate appropriate treatment. In order to exclude a sleep-related breathing disorder, to distinguish between obstructive and central sleep apnoea, or to diagnose other sleep disorders a cardiorespiratory polysomnography in a sleep laboratory is required. Polysomnography is also needed if comorbidities are present. Appropriate and prompt treatment of sleep-related breathing disorders can shorten cardiological rehabilitation and improve outcomes in this patient group. PMID- 22048329 TI - [Pleuritis in yellow nail syndrome]. AB - A 76-year-old man presented clinically with coughing and shortness of breath and was diagnosed radiologically to have massive pleural effusion as a combined feature of yellow nail syndrome. A lung biopsy was taken and revealed histologically: chronic non-specific inflammation in the pleuropulmonary border, intrapleural edema with eightfold pleural thickening in comparison to normal, angiogenesis in both the nutritive and functional intrapleural blood vessels, no abnormalities of lymphatic vessels with normal topographical distribution as detected by immunohistochemistry for antibody D2-40, granulomatous chronic foreign body reaction as a consequence of pleural effusion therapy by talcum pleurodesis.The histopathological findings of chronic non-specific pleuritis with angiogenesis and increased permeability of blood vessels led to massive intrapleural edema with pleural effusion. Abnormalities of lymphatic vessels could not be confirmed. Considering the features of this disease, they are probably secondary to chronic r infectious or immunological inflammation or paraneoplastic complications with angiogenesis (in about 19%). PMID- 22048330 TI - Experimental characterization of rupture in human aortic aneurysms using a full field measurement technique. AB - The present study aims at investigating biomechanical failure behaviour of human aneurismal aortic tissues so as to diagnose the rupture risk of aneurysms more accurately. An inflation test is performed on aneurismal aortic tissues up to failure and full-field measurements are achieved using stereo digital image correlation. Then, an appropriate constitutive model derived from histological structure of arteries is adopted to retrieve the Cauchy stress. The virtual fields method is used as an inverse procedure to identify material parameters. Next, the Cauchy stress components are calculated from the identified parameters and the measured Lagrange strain fields. Finally, an important stress parameter which can quantify the strength of aneurismal tissues is derived from the failure stress of aneurismal tissues. PMID- 22048331 TI - A molecular dynamics study of structure, stability and fragmentation patterns of sodium bis(2-ethylhexyl)sulfosuccinate positively charged aggregates in vacuo. AB - Positively charged supramolecular aggregates formed in vacuo by n AOTNa (sodium bis(2-ethylhexyl)sulfosuccinate) molecules and n(c) additional sodium ions, i.e. [AOT(n)Na(n+n(c))](n(c)), have been investigated by molecular dynamics (MD) simulations for n = 1-20 and n(c) = 0-5. Statistical analysis of physical quantities like gyration radii, atomic B-factors and moment of inertia tensors provides detailed information on their structural and dynamical properties. Even for n(c) = 5, all stable aggregates show a reverse micelle-like structure with an internal solid-like core including sodium counterions and surfactant polar heads surrounded by an external layer consisting of the surfactant alkyl chains. Moreover, the aggregate shapes may be approximated by rather flat and elongated ellipsoids whose longer axis increases with n and n(c). The fragmentation patterns of a number of these aggregates have also been examined and have been found to markedly depend on the aggregate charge state. In one particular case, for which experimental findings are available in the literature, a good agreement is found with the present fragmentation data. PMID- 22048332 TI - Effects of intermittent media replacement on the gene expression of differentiating neural progenitor cells. AB - A culture medium provides the major environmental conditions for cells in vitro. Replenishment of a culture medium causes an abrupt change in the extracellular environment for maintaining cells in a certain state. As a primitive form of a complex system, a stem cell is likely to be influenced by culture conditions that can change the destination of development. To understand how the change in extracellular environment can influence a biological system, we studied the effect of culture media replacement on the gene expression of differentiating neural progenitor cells. From time-series microarray gene expression data of neural progenitor cells, we observed a periodic wave that was synchronized with intermittent culture media replacement. We identified three modes that mostly contribute to the periodic patterns in gene expression and investigated mode related genes that are sensitive to the changes in the extracellular environment. The biological significance of the three modes was explored, such as progressive development and cell fate decision, extracellular matrix reassembly, and cell growth regulation in response to stress. In addition, we explored systemic influences of media replacement on differentiating neural progenitor cells. Intermittent culture media replacement interrupts expression of genes that participate in the major processes of differentiating neural progenitor cells. This study shows how the abrupt changes in the cell environment influence gene expression systematically. PMID- 22048333 TI - Lipid droplet meets a mitochondrial protein to regulate adipocyte lipolysis. PMID- 22048334 TI - A novel nuclear miRNA mediated modulation of a non-coding antisense RNA and its cognate sense coding mRNA. PMID- 22048335 TI - The clasp between NetrinG and NGL becomes crystal clear. PMID- 22048337 TI - Tight bifunctional hierarchical catalyst. AB - A new concept to prepare tight bifunctional catalysts has been developed, by anchoring CoMo(6) clusters on hierarchical ZSM-5 zeolites for simultaneous use in HDS and hydrocracking catalysis. The prepared material displays a significant improved activity in HDS catalysis compared to the impregnated counterpart. PMID- 22048338 TI - Frequency-comb-referenced molecular spectroscopy in the mid-infrared region. AB - A simple method for absolute-frequency measurements of molecular transitions in the mid-IR region is reported. The method is based on a cw singly resonant optical parametric oscillator (SRO), which is tunable from 3.2 to 3.45 MUm. The mid-IR frequency of the SRO is referenced to an optical frequency comb through its pump and signal beams. Sub-Doppler spectroscopy and absolute-frequency measurement of the P(7) transition of the nu3 band of CH4 are demonstrated. PMID- 22048339 TI - Fabrication of integrated waveguide grating in azo polymers. AB - In this Letter, we have introduced a technique, new to our knowledge, to fabricate gratings on a waveguide of azo-functionalized polymeric films using a slit mask and a fast, direct-writing method. To prevent the destruction of the waveguide by the grating formation on the waveguide, we placed a slit mask on the waveguide. By properly adjusting the resonance, this grating can be used as an integrated wavelength filter. We have produced an attenuation of 13.4 dB at 1562 nm with a FWHM of 3.45 nm. The grating has been fabricated as narrow as the width of the waveguide to couple filtered light into the waveguide by using a slit mask. Any light shifted from the resonance will pass through the waveguide undisturbed. PMID- 22048340 TI - Dual-wavelength laser source for onboard atom interferometry. AB - We present a compact and stable dual-wavelength laser source for onboard atom interferometry with two different atomic species. It is based on frequency doubled telecom lasers locked on a femtosecond optical frequency comb. We take advantage of the maturity of fiber telecom technology to reduce the number of free-space optical components, which are intrinsically less stable, and to make the setup immune to vibrations and thermal fluctuations. The source provides the frequency agility and phase stability required for atom interferometry and can easily be adapted to other cold atom experiments. We have shown its robustness by achieving the first dual-species K-Rb magneto-optical trap in microgravity during parabolic flights. PMID- 22048341 TI - High-speed phase imaging by parallel phase-shifting digital holography. AB - Parallel phase-shifting digital holography can obtain three-dimensional information of a dynamically moving object with high accuracy by using space division multiplexing of multiple holograms required for phase-shifting interferometry. We demonstrated high-speed parallel phase-shifting digital holography and obtained images of the phase variation of air caused by a compressed gas flow sprayed from a nozzle. In particular, we found the interesting phenomenon of periodic phase distributions. Reconstructed images were obtained at frame rates of 20,000 and 180,000 frames per second. PMID- 22048342 TI - Yb:CaGdAlO4 thin-disk laser. AB - We present the first demonstration of a Yb:CALGO thin-disk laser. In a slightly multimode configuration, we obtained up to 30 W of average power at a slope efficiency of 40% and an optical-to-optical efficiency of 32%. With a single-mode cavity, an average power of 25 W was achieved. A tuning range from 1018 to 1052 nm could be demonstrated by inserting a prism into the cavity. In the Q-switched regime, we obtained 1 mJ of pulse energy at a repetition rate of 100 Hz. PMID- 22048343 TI - Transverse mode control by manipulating gain distribution in a Yb:YAG ceramic thin disk. AB - We demonstrated that transverse mode can be controlled by manipulating gain distribution in a Yb:YAG ceramic thin disk. Several elongated higher order transverse modes of a Hermite-Gaussian beam were observed when a straight-line shaped gain region was created by using a diode laser output from an optical fiber. An orthogonally crossing pair of straight-line-shaped gain regions created with an additional optical fiber output resulted in the generation of a doughnut shaped Laguerre-Gaussian beam. This implies that easy and quick switching of Hermite-Gaussian and Laguerre-Gaussian beams is possible without mechanical handling. PMID- 22048344 TI - Lateral cavity photonic crystal surface-emitting laser with ultralow threshold. AB - A lateral cavity photonic crystal (PhC) surface-emitting laser is realized on a commercial epitaxial waveguide wafer without a distributed Bragg reflector first. Energy is coupled from the lateral resonance to surface-emitting light through the Gamma band edge of the PhC with a square lattice. Electrically driven 1553.8 nm surface-emitting lasing action is observed at room temperature. The threshold current density of 667 A/cm2 is ultralow for the surface-emitting laser. PMID- 22048345 TI - Generation of extreme ultraviolet vortex beams using computer generated holograms. AB - We fabricate computer generated holograms for the generation of phase singularities at extreme ultraviolet (EUV) wavelengths using electron beam lithography and demonstrate their ability to generate optical vortices in the nonzero diffraction orders. To this end, we observe the characteristic intensity distribution of the vortex beam and verify the helical phase structure interferometrically. The presented method forms the basis for further studies on singular light fields in the EUV frequency range, i.e., in EUV interference lithography. Since the method is purely achromatic, it may also find applications in various fields of x ray optics. PMID- 22048346 TI - Carrier-envelope phase stabilization with sub-10 as residual timing jitter. AB - We demonstrate carrier-envelope phase (CEP) stabilization of a mode-locked Ti:sapphire oscillator with unprecedented timing jitter of eight attoseconds. The stabilization performance is obtained by a combination of two different stabilization approaches. In a first step the drift of the CEP is stabilized with a conventional feedback loop by means of controlling the oscillator pump power with an acousto-optic modulator (AOM). In a second step we utilize a recently developed feed-forward type stabilization scheme which has a much higher control bandwith. Here an acousto-optic frequency shifter (AOFS) produces the stabilized output in the first diffraction order. Moreover, we present numerical results on the optimization of the length of the photonic crystal fiber, which is used to generate an octave-spanning spectrum, in order to optimize the sensitivity in the f-to-2f interferometers. PMID- 22048347 TI - Vector-dispersion compensation and pulse pedestal cancellation in a femtosecond nonlinear amplification fiber laser system. AB - We report on a femtosecond nonlinear amplification fiber laser system using a vector-dispersion compressor, which consists of a transmission grating pair and multipass cell based Gires-Tournois interferometer mirrors. The mirror is designed with nearly zero group-delay dispersion and large negative third-order dispersion. As a result, the third-order dispersion of the compressor can be adjusted independently to compensate the nonlinear phase shift of amplified pulses to reduce the pulse pedestal. With this scheme, the system outputs 44 fs laser pulses with little wing at 26.6 W output average power and 531 nJ pulse energy, corresponding to 10.8 MW peak power. PMID- 22048348 TI - Fluoride glass Raman fiber laser at 2185 nm. AB - We report on the first Raman laser based on a fluoride glass optical fiber. The Raman fiber laser was pumped by a 9.6 WTm3+:silica CW fiber laser operating at a wavelength of 1940 nm. A maximum output power of 580 mW was measured at 2185.1 nm, corresponding to a frequency shift of 579 cm(-1) (17.37 THz). We observed a threshold power of 3.8 W and a low power slope efficiency of 29% with respect to the launched pump power. Using those results and the known fiber parameters, we estimated a Raman gain peak value of 3.52*10(-14) m/W, which is lower than the previously reported values. PMID- 22048349 TI - Efficient adiabatic wavelength conversion in Gires-Tournois resonators. AB - We compare theoretically the performance capabilities of Fabry-Perot and Gires Tournois resonators when used for adiabatic wavelength conversion. It is shown that the Gires-Tournois device will exhibit superior performance and is able to convert the wavelength of optical pulses with >74% efficiency while nearly preserving their temporal duration. PMID- 22048350 TI - Modulation of the absorption coefficient at 1.3 MUm in Ge/SiGe multiple quantum well heterostructures on silicon. AB - We report modulation of the absorption coefficient at 1.3 MUm in Ge/SiGe multiple quantum well heterostructures on silicon via the quantum-confined Stark effect. Strain engineering was exploited to increase the direct optical bandgap in the Ge quantum wells. We grew 9 nm-thick Ge quantum wells on a relaxed Si0.22Ge0.78 buffer and a contrast in the absorption coefficient of a factor of greater than 3.2 was achieved in the spectral range 1290-1315 nm. PMID- 22048351 TI - Kilohertz laser frequency sensing with Brillouin mutually modulated cross-gain modulation. AB - Using mutually modulated cross-gain modulation, Stokes optical frequency changes are converted into modulation phase changes with high sensitivity. In the slow light transition regime, we demonstrate kilohertz sensitivity to the Stokes optical carrier frequency. The sensitivity is inversely proportional to the modulation frequency of the pump and Stokes beams. PMID- 22048352 TI - Low-cost adaptive astigmatism compensator for improvement of eye fundus camera. AB - In this work we show a conceptually simple and cheap means by which to improve retinal image quality in fundus cameras. We will explain how to build a low-cost variable astigmatism-correcting device with a pair of identical commercial ophthalmic lenses. We have developed and tested a low order aberration compensation device capable of correcting astigmatism prescriptions up to -8.00 D with no significant addition of higher order aberrations. A theoretical description of the device, calibration, and improvement in retinal images without employing any image restoration technique will be shown. PMID- 22048353 TI - High-accuracy three-dimensional position measurement of tens of micrometers size transparent microspheres using digital in-line holographic microscopy. AB - Digital in-line holographic microscopy has a strong potential in measuring various three-dimensional (3D) microscale flow phenomena. However, the axial elongation problem in reconstructing particles severely degrades the measurement accuracy along the light propagation direction. In this Letter, we utilize the lenslike characteristic of tens of micrometers size transparent spherical particles to extract their 3D position. A sharp intensity peak is observed in the reconstructed wave field, resulting from the light-focusing effect of the particle. As a result, the depth-of-focus constraint caused by the particle size is eliminated and the measurement accuracy is drastically improved up to submicrometer resolution. PMID- 22048354 TI - Variable-diameter refractive beam shaping with freeform optical surfaces. AB - We propose a refractive two-element system that converts the gaussian irradiance of an incident laser beam into a nominally flat-top output spot at a given distance with the capability to vary the spot diameter. The elements are high order freeform surfaces that, when laterally translated, form a variable composite beam shaper. The general approach for determining the required freeform surfaces is discussed, and example design results are presented. PMID- 22048355 TI - Proton beam writing of Nd:GGG crystals as new waveguide laser sources. AB - Focused proton beam writing has been utilized to fabricate optical channel waveguides in Nd:GGG crystals. The 1 MeV proton beam irradiation creates a local modified region with positive refractive index changes at the end of the proton trajectory, in which the channel waveguide could confine the light field in a symmetric way. Room-temperature laser emission has been achieved at 1063.7 nm, with absorbed pump power of 61 mW (at 808 nm). The obtained slope efficiency of the Nd:GGG waveguide laser system is as high as 66%, which is, to our best knowledge, the highest value for integrated lasers from ion beam processed channel waveguide systems. PMID- 22048356 TI - Multispectral optoacoustic tomography by means of normalized spectral ratio. AB - Quantification of biomarkers using multispectral optoacoustic tomography can be challenging due to photon fluence variations with depth and spatially heterogeneous tissue optical properties. Herein we introduce a spectral ratio approach that accounts for photon fluence variations. The performance and imaging improvement achieved with the proposed method is showcased both numerically and experimentally in phantoms and mice. PMID- 22048357 TI - Plasmonic Zener tunneling in metal-dielectric waveguide arrays. AB - We elucidate in this Letter plasmonic Zener tunneling (PZT) in metal-dielectric waveguide arrays (MDWAs) by using numerical simulations and theoretical analyses. PZT in MDWAs occurs at the waveguide entrance and wherever the beam completes Bloch oscillations, because the bandgap between the first and second bands is minimal at the center of the first Brillouin zone. This feature significantly differs from that of optical Zener tunneling in dielectric waveguide arrays. The dependence of the simulated tunneling rate on the gradient of the relative permittivity of the dielectric layers correlates with the tunneling theory, thus confirming the occurrence of PZT in MDWAs. PMID- 22048358 TI - One-dimensional single-shot thermometry in flames using femtosecond-CARS line imaging. AB - We report single-laser-shot one-dimensional thermometry in flames using femtosecond coherent anti-Stokes Raman scattering (fs-CARS) line imaging. Fs-CARS enables high-repetition-rate (1-10 kHz), nearly collision-free measurement of temperature and species concentration in reacting flows. Two high-power 800 nm beams are used as the pump and probe beams and a 983 nm beam is used as the Stokes beam for CARS signal generation from the N2Q-branch transitions at ~2330 cm(-1). The probe beam is frequency-chirped for single-laser-shot imaging. All three laser beams are formed into sheets and crossed in a line which forms the probe region. The resulting 1D line-CARS signal at ~675 nm is spatially and spectrally resolved and recorded as a two-dimensional (2D) image. Single-shot temperature measurements are demonstrated in flat-field flames up to temperatures exceeding 2000 K, demonstrating the potential of fs-CARS line imaging for high repetition-rate thermometry in turbulent flames. Such measurements can provide valuable data to validate complex turbulent-combustion models as well as increase the understanding of the spatio-temporal instabilities in practical combustion devices such as modern gas-turbine combustors and augmentors. PMID- 22048359 TI - Kr-PLIF for scalar imaging in supersonic flows. AB - Experiments were performed to explore the use of two-photon planar laser-induced fluorescence (PLIF) of krypton gas for applications of scalar imaging in supersonic flows. Experiments were performed in an underexpanded jet of krypton, which exhibited a wide range of conditions, from subsonic to hypersonic. Excellent signal-to-noise ratios were obtained, showing the technique is suitable for single-shot imaging. The data were used to infer the distribution of gas density and temperature by correcting the fluorescence signal for quenching effects and using isentropic relations. The centerline variation of the density and temperature from the experiments agree very well with those predicted with an empirical correlation and a CFD simulation (FLUENT). Overall, the high signal levels and quantifiable measurements indicate that Kr-PLIF could be an effective scalar marker for use in supersonic and hypersonic flow applications. PMID- 22048360 TI - CWDM source based on AlGaInAs/InP monolithically integrated DFB laser array. AB - The monolithic integration of four 1.5 MUm range AlGaInAs/InP distributed feedback lasers with a 4*1 multimode-interference optical combiner, a curved semiconductor optical amplifier, and an electro-absorption modulator using relatively simple technologies--sidewall grating and quantum well intermixing- has been demonstrated. The four channels span the wavelength range of 1530 to 1566 nm with a channel spacing of 12 nm. The epitaxial structure was designed to produce a far-field pattern as small as 21.2 degrees *25.1 degrees , producing a coupling efficiency with an angled-end single-mode fiber at twice that of a conventional device design. PMID- 22048361 TI - Fabry-Perot interferometers built by photonic crystal fiber pressurization during fusion splicing. AB - We report on a microscopic Fabry-Perot interferometer whose cavity is a bubble trapped inside an optical fiber. The microcavity is formed by pressuring a photonic crystal fiber (PCF) with large voids during fusion splicing with a conventional single-mode fiber. The technique allows achieving high repeatability and full control over the cavity size and shape. It was found that the size of the PCF voids contributes to control the cavity size independently of the pressure in the PCF. Our devices exhibit a record fringe contrast of 30 dB (visibility of 0.999) due to the ellipsoidal cavity whose surfaces compensate for the diffraction of the reflected beam. The strain sensitivity of the interferometers is higher when the cavities are ellipsoidal than when they are spherical. PMID- 22048362 TI - Large phase shift of spatial solitons in lead glass. AB - A large phase shift of the strongly nonlocal spatial optical soliton (SNSOS) was predicted by Guo et al. [Phys. Rev. E69, 016602 (2004)]. We investigate the phase shift of the SNSOS in lead glass. It is found that the phase shift rate along the propagating direction of such a soliton is one order larger than that of the local soliton. The theory agrees quantitatively with the experiment on the dependence of the phase shift on the degree of nonlocality. We realize a pi-phase shift by changing the optical power by about 10 mW around the critical soliton power, which agrees qualitatively with our theoretical result. PMID- 22048363 TI - Optical and magneto-optical resonances in nanocorrugated ferromagnetic films. AB - We report here on optical and magneto-optical spectra investigations of nanostructured Co and Ni films deposited on top of polymethyl methacrylate (PMMA) colloidal crystal. Resonant peculiarities have been observed in both spectra; their positions are scaled with the PMMA sphere diameter and depend on incident angle. Asymmetry of the resonance lineshapes as well as change of the direction of magneto-optical rotation has been observed. Both the surface plasmon resonance and the interference between reflections from the colloidal crystal and from the nanostructured film should be considered to explain the obtained results. PMID- 22048364 TI - Switching time in optically bistable injection-locked semiconductor lasers. AB - Switching between states in a dispersive bistable injection-locked slave laser has been theoretically investigated. We show that the switching can be achieved by relatively small and short (~10-50 ps) variation of the master laser injection power or frequency, which, besides the variation of the slave laser optical power, leads to significant variation of its photon phase (~5pi/6). By using an analytical model, we calculate the switching time dependence on the magnitude of the injection power and the frequency detuning variation. PMID- 22048365 TI - Reassessment of the electromagnetic reflection response of human skin at W-band. AB - Is the helical-coil form of the eccrine sweat-gland in humans suggestive of latent electromagnetic antenna function? In short, do humans possess in these saline, fluid-supporting, coil-structures, an extrasensory/signaling apparatus? This is the hypothesis of Feldman et al. [Phys. Rev. Lett. 100, 128102 (2008); Phys. Med. Biol. 54, 3341 (2009)] as they sort to correlate the mental state of a person with his or her W-band emission response. Ney et al. [Opt. Lett. 35, 3180 (2010); J. Biomed. Opt. 16, 067006 (2011)] subsequently contested this and demonstrated theoretically that multiple interference arising from the layered morphology of skin is the principal mechanism governing sub-THz electromagnetic functionality of human skin. This paper repeats the experimental work of Feldman et al. A quasi-optical reflectometer is employed and we observe extreme sensitivity from individual to individual in horn-antenna reflection measurements. Variability in dielectric properties and the layered morphology of human skin is confirmed to be the source of such sensitivity. Numerical modeling and experimental data together point to the key role of the sweat-duct in characterizing the phenomena of skin W-band resonance behavior. Significantly, however, we see no correlation between the mental state of a person and their W band reflection response. PMID- 22048366 TI - Pupil-segmentation-based adaptive optical microscopy with full-pupil illumination. AB - Optical aberrations deteriorate the performance of microscopes. Adaptive optics can be used to improve imaging performance via wavefront shaping. Here, we demonstrate a pupil-segmentation based adaptive optical approach with full-pupil illumination. When implemented in a two-photon fluorescence microscope, it recovers diffraction-limited performance and improves imaging signal and resolution. PMID- 22048367 TI - Correlation-induced spectral changes in tissues. AB - We report experimental evidence of correlation-induced spectral changes in biological tissues. The overall spectral shift in our transmission measurements is to the red and the mean wavelength of the original spectrum is up 10% larger. These results indicate that the spectral changes due to elastic scattering are significant and likely to hinder all spectroscopic measurements based on the inelastic (i.e., emission and absorption) interaction between light and tissues. Thus, simultaneous morphology and spectral measurements are required for accurate measurements spectroscopic information. PMID- 22048368 TI - Mid-IR femtosecond pulse generation on the microjoule level up to 5 MUm at high repetition rates. AB - We show efficient generation of mid-IR pulses tunable between 1 and 5 MUm from 100 kHz class femtosecond systems. The concept can be applied to various sources, particularly based on Ti:sapphire and the newly evolving Yb+ lasers. The mid-IR pulses are generated as the idler of a collinear optical parametric amplifier pumped by the laser fundamental. The seed for this amplifier is the idler of a previous amplification stage pumped with the second harmonic and seeded with a visible continuum. This enhances the energy and allows us to influence the bandwidth of the final output. Pulses with microjoule energy and Fourier limits of 50 fs are achieved. PMID- 22048369 TI - Subwave spikes of the orbital angular momentum of the vortex beams in a uniaxial crystal. AB - We have theoretically predicted gigantic spikes of orbital angular momentum caused by conversion processes of the centered optical vortex in the circularly polarized components of an elliptic vortex beam propagating perpendicularly to the crystal optical axis. We have experimentally observed the conversion process inside subwave deviations of the crystal length. We have found that the total orbital angular momentum of the wave beam is conserved. PMID- 22048370 TI - Understanding fractional-order surface plasmons. AB - We show experimentally that diffraction-induced surface plasmon excitation can mimic enhanced transmission and cause a highly sensitive modulation by the coherent interference between zero-order and reflected first-order diffraction in select regions of the terahertz spectrum. Based on the study of a one-dimensional metallic grating, we obtain the physical mechanisms of the fractional-order surface plasmon resonances observed with the two-dimensional grating of the metallic hole array. PMID- 22048371 TI - Sensitized broadband near-infrared luminescence from bismuth-doped silicon-rich silica films. AB - Developing Si compatible optical sources has attracted a great deal of attention owing to the potential for forming inexpensive, monolithic Si-based integrated devices. In this Letter, we show that ultra broadband near-IR (NIR) luminescence in the optical telecommunication window of silica optical fibers was obtained for Bi-doped silicon-rich silica films prepared by a co-sputtering method. Without excess Si, i.e., Bi-doped pure silica films, no luminescence was observed in the NIR range. A broad Bi-related NIR photoluminescence appears when excess Si was doped in the Bi-doped silica. The luminescence properties depended strongly on the amount of excess Si and the annealing temperature. Photoluminescence results suggest that excess Si acts as an agent to activate Bi NIR luminescence centers and also as an energy donor to transfer excitation energy to the centers. It is believed that this peculiar structure might find some important applications in Si photonics. PMID- 22048372 TI - Radiative and nonradiative decay rates in chromium-related centers in nanodiamonds. AB - We address for the first time the measurement of nonradiative decay rates in Cr related centers in nanodiamonds. Compared to our previous quantum efficiency measurement of Cr centers created in bulk diamond, separate measurements of radiative and nonradiative decay rates in grown nanodiamonds prove more challenging due to size dependence effects. We demonstrate in this Letter that, using defocused dipole imaging and collection efficiency calculation via finite difference time-domain (FDTD), a quantum efficiency up to 0.9 can be inferred to Cr-related centers showing a 2-level system photon statistics. PMID- 22048373 TI - All-optical pulse shaping for ultrawideband doublet pulses using nonlinear optical loop mirror with optical parametric amplification. AB - We propose and experimentally demonstrate an alternative photonic scheme for the generation of ultrawideband (UWB) doublet pulses, which is based on an optical fiber-based nonlinear optical loop mirror (NOLM) incorporating the optical parametric amplification (OPA) effect. The proposed scheme uses both cross-phase modulation and OPA within an optical fiber-based NOLM to produce an ideal transfer function for the shaping of input soliton pulses into doublet pulses. Using the proposed scheme, a successful conversion of input soliton pulses into doublet pulses is readily demonstrated. The system performance of UWB doublet pulses is also assessed by propagating the 1.25 Gbit/s doublet pulses over a fiber link. Error-free UWB doublet signal transmission is demonstrated. PMID- 22048374 TI - Widely wavelength switchable V-coupled-cavity semiconductor laser with ~40 dB side-mode suppression ratio. AB - We report the first experimental demonstration of a single-electrode-controlled digitally wavelength switchable V-coupled-cavity laser with high side-mode suppression-ratio (SMSR) in the 40 dB range. Sixteen-channel and twenty-six channel wavelength switchable lasers with 100 GHz spacing are demonstrated with the maximal SMSR of 40 dB and 37 dB, respectively. They do not require complex gratings, multiple epitaxial growths, or complex tuning algorithms. The device size is only 500 MUm*300 MUm. Such a simple, compact, and high-performance laser has great potential as a low-cost alternative to existing complex tunable lasers for wide deployment in optical networks and beyond. PMID- 22048375 TI - Fiber-delivered picosecond source for coherent Raman scattering imaging. AB - We demonstrate a two-color, fiber-delivered picosecond source for coherent Raman scattering (CRS) imaging. The wavelength-tunable picosecond pump is generated by nonlinear spectral compression of a prechirped femtosecond pulse from a mode locked titanium:sapphire (Ti:S) laser. The 1064 nm picosecond Stokes pulse is generated by an all-fiber time-lens source that is synchronized to the Ti:S laser. The pump and Stokes beams are combined in an optical fiber coupler, which serves not only as the delivery fiber but also as the nonlinear medium for spectral compression of the femtosecond pulse. CRS imaging of mouse skin is performed to demonstrate the practicality of this source. PMID- 22048376 TI - Femtosecond laser-induced breakdown in distilled water for fabricating the helical microchannels array. AB - We have fabricated complex helical microchannel arrays with uniform diameter in silica glass using femtosecond laser-induced breakdown in distilled water. The generated high-speed jet and shockwave cause cavitation damage in silica glass. Distilled water injected into microchannels through a rubber hose is used for effectively ejecting the debris. The low concentration of debris in the ablated area ensure continuously femtosecond laser-induced breakdown. The distribution, coil number, coil diameter and pitch of the helical microchannel arrays can be controlled. PMID- 22048377 TI - Passive harmonic mode locking of soliton crystals. AB - We report experimental observation of passive harmonic mode locking (HML) in which the basic pattern is a soliton crystal. Several crystal states were generated from an initial large bound state by increasing the pump power. The soliton crystals are identical and progressively span along the cavity to finally take a regular spacing leading to HML of solitons crystal. PMID- 22048378 TI - Resolution enhancement of random adsorbed single-molecule localization based on surface plasmon resonance illumination. AB - Single-molecule localization (SML) is a powerful tool to overcome the diffraction limit in optical imaging, because the fluorescence emitted by single molecules can be observed with nanometer accuracy when the optical background and associated noise are made sufficiently small. Random adsorbed SML has been successfully demonstrated for superresolution imaging on metal surfaces. To optimize the random adsorbed SML, we developed a new illumination method based on surface plasmon resonance (SPR). The enhancement of the fluorescence signal and the reduction of background noise were achieved simultaneously. A high localization resolution of 15 nm was demonstrated with this new SPR illumination system. PMID- 22048379 TI - Dual-band double-negative-index fishnet metamaterial at millimeter-waves. AB - An effective negative refractive index (NRI) is demonstrated and experimentally verified for the first two propagation bands of a fishnet-like metamaterial at millimeter-wave frequencies. The dual-band NRI behavior is achieved by engineering the diffraction order (+/-1, +/-1) associated with the internal mode supported between holey layers to correspond with the second propagation band. In addition to the experimental interferometric technique that accounts for the handedness of the propagation, numerical results are given to predict the dual band effective NRI and to confirm dual-band negative refraction for a prism composed of the proposed metamaterial. PMID- 22048380 TI - Effects of twisting and bending on LP21 mode propagation in optical fiber. AB - Twisting and bending characteristics of low-multimode LP21 mode propagation in optical fibers is presented for the first time. Theoretical fiber mode modeling, combining geometrical rotation with opto-elastic effects, demonstrates that the propagation of the LP21 mode is bending-effect-immune. Experimental testing verifies that the LP21 mode specklegram rotates 0.9112 of the fiber twist angle in a fused silica fiber, independent of any fiber bending. This characteristic allows for the LP21 mode to be highly applicable in fiber specklegram sensors. PMID- 22048381 TI - High-order diffraction suppression using modulated groove position gratings. AB - Conventional diffraction gratings composed of a series of equally spaced slits suffer from wavelength overlapping caused by high-order diffraction. Here modulated groove position gratings (MGPGs) are proposed to significantly suppress the high diffraction orders. Both numerical solution and experimental results demonstrate the effectiveness of MGPGs. The suppression ratio is determined by the number of grating grooves used. By using an MGPG with 10,000 grooves, a suppression ratio as high as 18,000 can be obtained. In addition, the minimum linewidth is kept to 1/4 of the grating period, which enables grating realization with high line density employing today's nanofabrication technology. Our results should be of great interest in both diffraction grating theory and applications, particularly due to MGPGs' applicability in a wide wavelength range and realizability with high line density. PMID- 22048382 TI - Ultracompact nonreciprocal optical isolator based on guided resonance in a magneto-optical photonic crystal slab. AB - We design an ultracompact optical isolator with normal incident geometry that operates with a bandwidth that is substantial for a device of this size. For operation in a telecommunication wavelength of 1.55 MUm, the thickness of the device is less than 1 MUm and the device supports an operating bandwidth of 400 GHz over which the minimum contrast ratio exceeds 25 dB. Our design utilizes guided resonance in a photonic crystal slab to enhance magneto-optical effects, and exploits interference effects among multiple resonances to create desired transmission spectral line shapes. PMID- 22048383 TI - Optical manipulation of microparticles using whispering-gallery modes in a silicon nitride microdisk resonator. AB - We demonstrate optical manipulation of 1 MUm sized polystyrene microparticles on silicon nitride microdisk resonator devices using whispering-gallery modes in an integrated optofluidic chip. We demonstrate multiple trapping tracks and extended trapping ranges within single wavelengths through exciting high-order modes. We observe various sets of trapping tracks and ranges through exciting various resonance modes. We switch particle traveling tracks by tuning the laser wavelength to various wavelengths. We also observe microparticles assembling along the trapping tracks. PMID- 22048384 TI - All-optical multiple-channel logic XOR gate for NRZ-DPSK signals based on nondegenerate four-wave mixing in a silicon waveguide. AB - We report an all-optical multiple-channel exclusive OR (XOR) gate for 10 Gbits/s non-return-to-zero differential phase-shift keying (NRZ-DPSK) signals using nondegenerate four-wave mixing in a silicon waveguide. The function of the logic XOR gate is experimentally demonstrated using 40 bit DPSK sequences. Also, the eye diagram of the XOR signal is clearly observed as the incident signals are both modulated by DPSK sequences originating from 2(31)-1 pseudorandom binary sequences. PMID- 22048385 TI - Synthetic aperture microscopy for high resolution imaging through a turbid medium. AB - We report on synthetic aperture microscopy through a highly turbid medium. We first recorded a transmission matrix for the turbid medium with an angular basis of 20,000 complex images covering 0.6 NA. This effectively converts the medium into a lens of the same NA. Distorted images of a target object are then taken at 500 different angles of illumination covering 0.6 NA. For each of the distorted images, the original object image is reconstructed from the transmission matrix by the recently developed turbid lens imaging (TLI) technique. All 500 reconstructed images are synthesized to enhance the NA to 1.2 and thereby generate an object image with twice the enhanced spatial resolution of the individual images. Our method of applying aperture synthesis for TLI makes it possible to enhance the resolving power without increasing the number of transmission matrix elements. This relieves the demand for data acquisition and processing that has impeded the practicality of TLI. PMID- 22048386 TI - High conversion efficiency fiber optical parametric oscillator. AB - We present a chi(3) fiber parametric oscillator with high conversion efficiency from the input pump wave to the output parametric sidebands. By introducing an intracavity filter detuned from the oscillator's phase-matched frequency conversion efficiencies considerably higher than those possible when operating at the phase-matched frequency are demonstrated. Experimentally we are able to obtain a total internal conversion efficiency in excess of 93% from the pump to the Stokes and anti-Stokes sidebands. PMID- 22048387 TI - Fiber coupler for generating orbital angular momentum modes. AB - We propose a fiber coupler consisting of a central ring and four external cores to generate up to ten orbital angular momentum (OAM) modes. Four coherent input lights are launched into the external cores and then coupled into the central ring waveguide to generate OAM modes. By changing the size of the external cores, one can selectively excite a high-order OAM mode. The quality of the generated OAM modes can be enhanced by adjusting the polarization state and the phase of input lights. We show the generation of OAM modes with odd charge numbers of -9 to +9 (i.e., 10 modes totally) with mode purity of >99% using <2 mm long fiber. This fiber coupler design can be extended to enable all-fiber spatial-mode (de)multiplexing. PMID- 22048388 TI - Effect of varying pore size of AAO films on refractive index and birefringence measured by prism coupling technique. AB - Anodic aluminum oxide (AAO) films with different pore sizes were prepared to modulate the effective refractive index and birefringence. To investigate the relationship between the refractive index and the pore size of the AAO film, optical constants were obtained using a prism coupler with various lasers. With experimental results, the dispersion curve of alumina itself without pores was extracted using a theoretical anisotropic model. We demonstrated that AAO films could offer a wide range of refractive index and birefringence values for optical device applications. Furthermore, index profiles as a function of the thickness of the AAO films were obtained by inverse Wentzel-Kramer-Brillouin approximation to examine the optical homogeneity. PMID- 22048389 TI - Accurate estimation of Brillouin frequency shift in Brillouin optical time domain analysis sensors using cross correlation. AB - Current methods of estimating the Brillouin frequency shift in Brillouin optical time domain analysis sensors are based on curve-fitting techniques. These techniques apply the same weight to all portions of the curve and dutifully fit into the peak and noisy ends of the curve. This makes them very sensitive to noise, initialization of fitting parameters, symmetry, and start and stop frequencies. We introduce a method based on the cross-correlation technique to estimate the central frequency of noisy Lorentzian curves, which is more robust to noise and free from initial settings of fitting parameters. PMID- 22048390 TI - Long-range dielectric-loaded surface plasmon polariton waveguides operating at telecommunication wavelengths. AB - We report on the realization of long-range dielectric-loaded surface plasmon polariton waveguides (LR-DLSPPWs) consisting of straight and bent subwavelength dielectric ridges deposited on thin and narrow metal stripes supported by a dielectric buffer layer covering a low-index substrate. Using imaging with a near field optical microscope and end-fire coupling with a tapered fiber connected to a tunable laser at telecommunication wavelengths (1425-1545 nm), we demonstrate low-loss (propagation length ~500 MUm) and well-confined (mode width ~1 MUm) LR DLSPPW mode guiding and determine the propagation and bend loss. PMID- 22048391 TI - Mode-shape measurement of piezoelectric plate using temporal speckle pattern interferometry and temporal standard deviation. AB - This study proposes an image processing method to improve the quality of interference fringes in mode-shape measurement using temporal speckle pattern interferometry. A vibrating piezoelectric plate at resonance was investigated, and the full-field optical information was saved as a sequence of images. According to derived statistical properties, an algorithm was developed to remove noise from both the background and disturbance, resulting in high-resolution images of excellent quality. In addition, the resonant frequency and mode shape obtained using the proposed algorithm demonstrate excellent agreement with theoretical results obtained by the finite element method. PMID- 22048392 TI - First laser oscillation and broad tunability of 1 at. % Yb-doped Sc2O3 and Lu2O3 ceramics. AB - We report the first oscillation achieved on 1 at. % Yb-doped Sc2O3 and Lu2O3 ceramics under quasi-CW pumping at 968 nm. With Sc2O3 we measured a maximum output power of 2.2 W with a slope efficiency of 59% at 1040.5 nm. Comparable results are obtained with Lu2O3 at 1032.5 nm, i.e., 1.8 W with a corresponding slope of 45%, while at 1078 nm we measured 1.5 W with 34% of slope efficiency. Finally, we present the range of tunability, which exceeds 41 nm for both samples. To the best of our knowledge, these are the first measurements reported in literature either in terms of laser emission or continuous tunability range achieved with 1 at. % doping level. PMID- 22048393 TI - High temperature and wavelength dependence of avalanche gain of AlAsSb avalanche photodiodes. AB - The evolution of the dark currents and breakdown at elevated temperatures of up to 450 K are studied using thin AlAsSb avalanche regions. While the dark currents increase rapidly as the temperature is increased, the avalanche gain is shown to only have a weak temperature dependence. Temperature coefficients of breakdown voltage of 0.93 and 1.93 mV/K were obtained from the diodes of 80 and 230 nm avalanche regions (i-regions), respectively. These values are significantly lower than for other available avalanche materials at these temperatures. The wavelength dependence of multiplication characteristics of AlAsSb p-i-n diodes has also been investigated, and it was found that the ionization coefficients for electrons and holes are comparable within the electric field and wavelength ranges measured. PMID- 22048394 TI - Reconfigurable optical differential phase-shift-keying pattern recognition based on incoherent photonic processing. AB - We propose and experimentally demonstrate asynchronous optical differential phase shift-keying (DPSK) pattern recognition using a fully reconfigurable technique. The proposed method uses optical phase-to-bipolar intensity conversion through all-optical differentiation in conjunction with an incoherent time-spectrum convolution system where the pattern to be recognized is implemented directly in the spectral domain through optical amplitude-only linear filtering. Full reconfigurability in terms of bit rate, pattern sequence, and pattern length is achieved using electronically programmable optical filters. We demonstrate dynamically switching recognition of different 64 bit patterns in a continuous 12 Gb/s DPSK pseudorandom optical bit stream with contrast ratio up to 3.8 dB. PMID- 22048395 TI - Optical isolator using two tandem phase modulators. AB - We propose and demonstrate an integrated optical isolator in InP using two phase modulators in series. The phase modulators are driven with a single-frequency signal in quadrature. Theoretically there is no effect on the forward signal, and the carrier of the backward signal can be eliminated, the energy distributed to other frequencies. We achieve a carrier isolation of 11 dB and an excess insertion loss of 2.3 dB. Such an isolator can be monolithically integrated with a laser without extra materials or magnetic fields. PMID- 22048396 TI - Oxygen vacancy density-dependent transformation from infrared to Raman active vibration mode in SnO2 nanostructures. AB - Raman spectra acquired from spherical, cubic, and cuboid SnO2 nanocrystals (NCs) reveal a morphologically independent Raman mode at ~302 cm(-1). The frequency of this mode is slightly affected by the NC size, but the intensity increases obviously with decreasing NC size. By considering the dipole changes induced by oxygen vacancies and derivation based on the density functional theory and phonon confinement model, an oxygen vacancy density larger than 6% is shown to be responsible for the transformation of the IR to Raman active vibration mode, and the intensity enhancement is due to strong phonon confinement. PMID- 22048397 TI - Low phase noise diode laser oscillator for 1S-2S spectroscopy in atomic hydrogen. AB - We report on a low-noise diode laser oscillator at 972 nm actively stabilized to an ultrastable vibrationally and thermally compensated reference cavity. To increase the fraction of laser power in the carrier we designed a 20 cm long external cavity diode laser with an intracavity electro-optical modulator. The fractional power in the carrier reaches 99.9%, which corresponds to an rms phase noise of phi(rms)2=1 mrad2 in 10 MHz bandwidth. Using this oscillator, we recorded 1S-2S spectra in atomic hydrogen and have not observed any significant loss of the excitation efficiency due to phase noise multiplication in the three consecutive two-photon processes. PMID- 22048398 TI - Dipole response of spaser on an external optical wave. AB - We find the conditions upon the amplitude and frequency of an external electromagnetic field at which the dipole moment of a Bergman-Stockman spaser oscillates in antiphase with the field. For these values of the amplitude and frequency the loss in metal nanoparticles is exactly compensated by the gain. This shows that spasers may be used as inclusions in designing lossless metamaterials. PMID- 22048399 TI - Phase-shifting Zernike phase contrast microscopy for quantitative phase measurement. AB - Zernike phase contrast microscopy is extended and combined with a phase-shifting mechanism to perform quantitative phase measurements of microscopic objects. Dozens of discrete point light sources on a ring are constructed for illumination. For each point light source, three different levels of point-like phase steps are designed, which are alternatively located along a ring on a silica plate to perform phase retardation on the undiffracted (dc) component of the object waves. These three levels of the phase steps are respectively selected by rotating the silica plate. Thus, quantitative evaluation of phase specimens can be performed via phase-shifting mechanism. The proposed method has low "halo" and "shade-off" effects, low coherent noise level, and high lateral resolution due to the improved illumination scheme. PMID- 22048400 TI - Method for measuring liquid phase diffusion based on tilted fiber Bragg grating. AB - We propose and experimentally demonstrate a method for measuring liquid phase diffusion based on tilted fiber Bragg grating (TFBG). By monitoring the transmission spectra of the TFBG placed at different positions of the diffusion zone and calculating the normalized area enclosed by the upper and lower envelope curves of the cladding modes, the distribution curves of the glycerol concentration are obtained, according to the experimental calibration formulas between the glycerol concentration and the normalized area. This method can conveniently achieve remote and distributed measurement of the liquid phase diffusion in hostile environment because of its all-fiber structure. PMID- 22048401 TI - Direct probing of ion pair formation using a symmetric triangulenium dye. AB - The 2,6,10-tris(dialkylamino)trioxatriangulenium dyes (ATOTA(+)) are highly stabilised cationic chromophores with D(3h) symmetry. The symmetry gives rise to a degeneracy of the main electronic transition. In low polarity solvents significant splitting of this degenerate transition is observed and assigned to ion pair formation. Ion pairing of the 2,6,10 tris(dioctylamino)trioxatriangulenium ion with Cl(-), BF(4)(-), PF(6)(-) and TRISPHAT anions was studied using absorption spectroscopy. A clear correlation is found between the size of the anion and the splitting of the ATOTA(+) transitions. In benzene the Cl(-) salt displays a splitting of 1955 cm(-1), while the salt of the much larger TRISPHAT ion has a splitting of 1543 cm(-1). TD-DFT calculations confirm the splitting of the states and provide a detailed insight into the electronic structure of the ion pairs. The different degree of splitting in different ion pairs is found to correlate with the magnitude of the electric field generated in each ion pair, thus leading to the conclusion that the effect seen is an internal Stark effect. By insertion of an amphiphilic derivative of the ATOTA(+) chromophore in an oriented lamellar liquid crystal, it was possible to resolve the two bands of the double peak spectrum and show their perpendicular orientation in the molecular framework, as predicted by the calculations. PMID- 22048402 TI - Expert's comment concerning Grand Rounds case entitled "Limited access surgery for 360 degrees in situ fusion in a dysraphic patient with high grade spondylolisthesis" (by M. A. Konig and B. M. Boszczyk). AB - The case of a 26 year-old woman with high grade spondylolisthesis, history of diastematomyelia and tethered cord, with acute onset of back pain and bilateral sciatica after a fall. This comment will focus on three issues: indication for surgery, indication for reduction and levels to be included in fusion. Surgery is indicated in this case for intermittent urinary incontinence and saddle anesthesia, and failure of conservative treatment to control pain. Other important determinant of surgical indication is risk of progression, depending rather on the degree of dysplasia as classified by Marchetti-Bartolozzi than on the degree of slip as classified by Meyerding. High dysplastic olisthesis is identified by excessive pelvic retroversion. Reduction is indicated in patients with high torque through L5-S1. L5 severity index (SI) correlates with the magnitud of torque through L5-S1. Similarly, the decision to include L4 in fusion can be made based on the value of SI for L4. PMID- 22048403 TI - Congenital kypho-scoliosis: a case of thoracic insufficiency syndrome and the limitations of treatment. AB - INTRODUCTION: Congenital spinal vertebral anomalies may present with deformity resulting in congenital scoliosis and kyphosis. This leads to abnormal spinal growth. The latter when combined with associated rib fusions may impair normal thoracic cage development and resultant pulmonary hypoplasia. Most congenital scoliosis can be detected in utero by ultrasound scan or recognized in the neonatal period, but a few spinal defects can remain undetected. MATERIALS AND METHODS: In this Grand Round, we present the case of a 7-year-old girl with a severe scoliosis and thoracic insufficiency syndrome (TIS). 3D CT reconstruction imaging demonstrated a mixed picture of fusion and segmentation abnormalities. A marked kyphoscoliosis was demonstrated at the thoraco-lumbar junction. Via a left thoracotomy, anterior excision of intervertebral discs was performed together with, interbody fusion, and in situ stabilisation of the kyphosis with double allograft (femur) strut grafts. CONCLUSIONS: This article highlights the features of congenital kypho-scoliosis and TIS. The difficulties of treating kyphosis when combined with TIS are discussed together with the limitations of current surgical techniques. PMID- 22048404 TI - Reviewer's comment concerning "Spinous process morphology: the effect of ageing through adulthood on spinous process size and relationship to sagittal alignment" (doi:10.1007/s00586-011-2029-6 by C.E.W. Aylott, R. Puna, P.A. Robertson, C. Walker). PMID- 22048405 TI - Acute low back pain in high school adolescents in Southern Brazil: prevalence and associated factors. AB - PURPOSE: The aim of this study was to investigate the prevalence of acute low back pain (ALBP) and associated factors in high school students from a Southern Brazilian city. METHODS: The study was cross-sectional and interviewed 1,233 students 13- to 19-year-olds, attending high schools. A total of 25 schools were included in the sample (15 state institutions, 7 private, 2 federal and 1 municipal). The ALBP was evaluated using two questions. The outcome was LBP in the previous 30 days. RESULTS: The prevalence of ALBP was 13.7%. Non-white students, who commuted to school walking, showed a higher prevalence of ALBP. The prevalence of ALBP is relatively high. CONCLUSIONS: Further studies with follow ups to adulthood are needed to investigate whether physical cumulative loads on the lumbar spine (for example, duration/transport, school bags and inadequate school furniture) during adolescence, may influence the development of ALBP later in life. PMID- 22048406 TI - Do platform-specific factors explain microRNA profiling disparities? PMID- 22048407 TI - Synthesis, crystal structure and properties of a new candidate for nonlinear optical material in the IR region: Hg2BrI3. AB - The synthesis, crystal structure, nonlinear optical (NLO) property and some other properties of a new material, Hg(2)BrI(3), are reported. The crystal structure has been established by single crystal X-ray diffraction studies. Hg(2)BrI(3) belongs to the HgBrI type and crystallizes in the orthorhombic space group Cmc21 (No. 36). The compound shows a phase-matchable second harmonic generation (SHG) of about 1.2 times as strong as that of KTiOPO(4) (KTP) based on the powder SHG measurement. It exhibits a wide transparency in the IR region (from 2.5 to 30 MUm), and a good thermal stability. It is believed that Hg(2)BrI(3) is a new candidate for NLO materials in the IR region. PMID- 22048408 TI - Scientific communication: writing up. PMID- 22048411 TI - SHARPINing integrin inhibition. AB - The activity state of integrins is crucial for cell adhesion, migration and differentiation, and is regulated predominantly by protein interactions of the integrin beta cytoplasmic domain. SHARPIN is now shown to negatively regulate integrin activation by binding the alpha-integrin subunit and interfering with the association of the beta cytodomain with activating proteins. PMID- 22048410 TI - Nuclear actin and myosins: life without filaments. AB - Actin and myosin are major components of the cell cytoskeleton, with structural and regulatory functions that affect many essential cellular processes. Although they were traditionally thought to function only in the cytoplasm, it is now well accepted that actin and multiple myosins are found in the nucleus. Increasing evidence on their functional roles has highlighted the importance of these proteins in the nuclear compartment. PMID- 22048417 TI - The impact of an emergency motorcycle response vehicle on prehospital care in an urban area. AB - INTRODUCTION: Faster emergency response times are generally considered to have a positive effect on life expectancy of patients with a life-threatening event, leading many communities to determine response time intervals. However, worldwide, increasing urbanization and traffic congestion threatens ambulance response times. An emergency motorcycle response vehicle (MRV) can overcome these hurdles more easily than a larger ambulance. It also offers dispatch flexibility in responding to calls estimated to have a low likelihood of a patient who needs transport. The first aim of this study was to determine whether an MRV can shorten response times and impact on resuscitation outcomes in a heavily urbanized and densely populated region in the Netherlands. The second aim was to evaluate differences in dispatch and transport between MRV and ambulance. METHODS: This was a nonrandomized, prospective cohort study comparing an MRV unit with regular ambulances in a Dutch city of 265 000 people. Included were all 'urgent patient' cases within operating time of the MRV between January 2003 and August 2003. RESULTS: A total of 1664 patients was evaluated, including 468 motorcycle and 1196 ambulance responses. Use of MRVs led to a decrease in response time of 54 s (P<=0.01). We could not show a decrease in mortality risk in cases of resuscitation [relative risk (RR): 2.50, confidence interval (CI): 0.17-36.21]. There was a slightly improved 1-year survival in other life threatening cases (RR: 1.13, CI: 1.03-1.24). However, this is most likely because of differences in dispatch decisions (the MRV is sent to 'lighter' cases) and not because of faster assistance. The MRV paramedic was more likely to treat and release the patient (RR: 2.21, CI: 1.80-2.73) or refer them to a general practitioner (RR: 2.11, CI: 1.73-2.58) and much less likely to refer them to the hospital emergency department (41.2 vs. 72.6%). Referrals to the hospital by the MRV were mostly by the patient's own means of transportation (RR: 13.14, CI: 5.89 29.32) rather than by ambulance. CONCLUSION: Using motorcycles in a Dutch setting lead to better emergency medical service response times. The MRV serves a different population. Resulting in a higher treat and release rate and less transportation to hospital. PMID- 22048418 TI - Femoral neck stress fracture and femoroacetabular impingement. AB - The patient was a 34-year-old male recreational marathon runner referred to a physical therapist with a chief complaint of worsening right lateral hip pain of 3 months duration that was insidious in nature. Following a physical examination, the physical therapist discussed his suspicions with the referring physician. Magnetic resonance imaging revealed findings consistent with a stress fracture at the inferomedial right femoral neck, a mild cam-type deformity of the right femoral neck, and a mild degree of heterogeneity of the right superior anterior labrum, representing a possible tear. PMID- 22048419 TI - Long-term outcome in patients with carotid artery stenting and contralateral carotid occlusion: a single neurovascular center prospective analysis. AB - INTRODUCTION: The aim of this study was to analyze the clinical features and early and late outcome of patients treated with carotid artery stenting for carotid stenosis with occlusion of the contralateral vessel (CAS-CCO), and compare them to patients without occlusion (CAS-NO). METHODS: From 1999 through 2010, 426 patients with 479 procedures were prospectively recorded, 61 patients (14.3%) CAS-CCO, and 365 patients CAS-NO. Immediate CAS complications, complications within the first 30 days and long-term complications were documented through annual clinical and ultrasonological follow-up visits. Stenosis rate was recorded. RESULTS: Patients with mean age of 68.4 years, 80% men had: (1) periprocedural stroke in three cases (0.7%), (2) cumulative 30-day stroke, ischemic cardiopathy, and death in 4.2%, without differences between groups (CAS-CCO 3.3%, CAS-NO 4.4%). Mean follow-up period was 55 +/- 32.78 months, median 56 months. (3) Stroke during the follow-up in 8%, without differences between CAS-CCO and CAS-NO groups (3.7% and 8.8%). (4) Myocardial infarction in 11.2% and (5) global mortality in 24.3%, without statistical differences between groups. Of the 254 cases enrolled in the restenosis analysis, 44 patients (17.3%) had restenosis of any grade during a mean follow-up period of 52 months, without statistical differences between CAS-CCO and CAS-NO groups. Only 7.5% presented restenosis >= 50%. Its occurrence was statistically associated with previous neck radiation. CONCLUSIONS: Periprocedural risks and long-term outcomes of patients treated with CAS and presenting a contralateral carotid occlusion does not differ from regular patients treated with CAS. Based on the low stenosis rate of our study, our results do not give credit to extra surveillance measures in patients with contralateral carotid occlusion. PMID- 22048421 TI - Water and sanitation issues for persons with disabilities in low- and middle income countries: a literature review and discussion of implications for global health and international development. AB - The critical importance of unrestricted access to clean drinking water and basic sanitation for all is highlighted in Millennium Development Goal 7, which calls for the reduction by half of the proportion of people without such access by 2015. Unfortunately, little attention has been paid to the needs of such access for the one billion people living with a disability worldwide, despite the fact that the right to equal access for all international development initiatives is guaranteed in the new United Nations Convention on the Rights of Persons with Disabilities. In this paper, we review what is currently known about access to water and sanitation for persons with disabilities in low- and middle-income countries from the perspective of both international development and global health, and identify existing gaps in research, practice and policy that are of pressing concern if the water and sanitation needs of this large - and largely overlooked - population are to be addressed. PMID- 22048420 TI - The role of carrier number on the procoagulant activity of tissue factor in blood and plasma. AB - Tissue factor (TF) is a transmembrane glycoprotein cofactor of activated blood coagulation factor VII (FVIIa) that is required for hemostatic thrombin generation at sites of blood vessel injury. Membrane-associated TF detected in circulating blood of healthy subjects, referred to as intravascular or circulating TF has been shown to contribute to experimental thrombus propagation at sites of localized vessel injury. Certain disease states, such as metastatic cancer, are associated with increased levels of intravascular TF and an elevated risk of venous thromboembolism. However, the physiological relevance of circulating TF to hemostasis or thrombosis, as well as cancer metastasis, is ill defined. This study was designed to assess whether the spatial separation of intravascular TF carriers in blood, demonstrated with TF-inducible human monocytic cell line U937 or TF-coated polymer microspheres, affected procoagulant activity and hence thrombogenic potential. Experiments were performed to characterize the effects of TF-carrier number on the kinetics of clot formation in both open and closed systems. The procoagulant activity of TF carriers was found to correlate with spatial separation in both closed, well-mixed systems and open, flowing systems. TF carriers enhanced the amidolytic activity of FVIIa toward the chromogenic substrate, S-2366, as a function of carrier count. These results suggest that TF-initiated coagulation by circulating TF is kinetically limited by mass transport of TF-dependent coagulation factors to the TF-bearing surface, a constraint that may be unique to circulating TF. Spatial separation of circulating TF carriers is therefore a critical determinant of the procoagulant activity of circulating TF. PMID- 22048422 TI - Away-from-home drinking water consumption practices and the microbiological quality of water consumed in rural western Kenya. AB - A cross-sectional descriptive study was conducted to examine away-from-home drinking water consumption practices and the microbiological quality of water consumed in rural western Kenya. The study involved adults and schoolchildren. Data were collected using focus group discussions, questionnaire survey, observations, diaries and interviews. The findings suggest that away-from-home drinking water consumption is a common practice in the study area; however, the microbiological quality of the water consumed is poor. While some respondents perceive the water to be safe for drinking mainly because of the clear colour of the water, others are forced by circumstances to drink the water as it is owing to a lack of alternative safe sources. It is concluded that there is a need for new innovative approaches to address away-from-home drinking water consumption in resource-poor settings in order to complement and maximize the benefits of point of-use water treatment at the household level. PMID- 22048423 TI - Quantitative PCR-based detection of pathogenic Leptospira in Hawai'ian coastal streams. AB - Pathogenic Leptospira, the causative agents of leptospirosis, are mainly associated with tropical freshwaters, but little is known about their fate in the environment. This study analyzed the distribution of pathogenic Leptospira genomes in 22 tropical coastal streams using quantitative polymerase chain reaction (qPCR). Statistical analyses were conducted to understand pathogenic Leptospira associations with water quality parameters, land use, microbial source tracking (MST) markers, and fecal indicators. Results indicated that pathogenic Leptospira genomes were widespread in O'ahu coastal streams during the Hawai'ian rainy season, with slightly higher concentrations in December when compared with March. Leptospira showed a strong positive association to turbidity, a finding consistent with studies showing increased Leptospira survival when aggregated to particles. Positive correlations to salinity may also indicate survival of Leptospira in relatively saline stream waters. A positive association to the human Bacteroidales fecal marker, no correlation to pig or cow Bacteroidales markers, and a negative association to agricultural land coverage may suggest human or other non-agricultural animal sources of Leptospira (e.g., rats or dogs). Future studies of Leptospira in the Hawai'ian environment are recommended to investigate Leptospira survival in saline waters, to determine both primary and secondary Hawai'ian animal hosts of Leptospira, and to correlate environmental exposures with epidemiological studies of leptospirosis. PMID- 22048424 TI - Impact of cleaning regimes on dental water unit contamination. AB - Microorganisms that have been identified in dental unit waterlines (DUWLs) are of concern because they can cause infections, especially in immunocompromised patients. This study aimed to assess the incidence of microbial contamination in DUWLs before and after intervention to reduce contamination, and to investigate the presence of coliforms, Escherichia coli and Pseudomonas aeruginosa. Water samples were collected aseptically from the waterlines. The high-speed hand-piece and dental chair units were served by one distillation apparatus, which was fed by the potable tap water of four dental clinics. Different interventions were used: chlorination, flushing before clinics and between patients, draining at the end of the day, and freshly distilled water on a daily basis. There was a significant difference between the level of contamination in the high-speed hand piece (1.5-2.7 log CFU/ml) and dental chair unit water (2.0-3.5 log CFU/ml). Coliforms (0.9%) E. coli (0.9%) and Pseudomonas (1.8%) were detected during 2008. This study indicates the need to monitor water quality regularly and prevent stagnation in DUWLs to reduce the number of viable bacteria to <100 CFU/ml. We recommend flushing the DUWL for 2 min before the first patient and for 10-20 s between patients, flushing the dental unit at the end of the day and draining it overnight to reduce the development of biofilms, and chlorination of the DUWLs. PMID- 22048425 TI - Disposable swim diaper retention of Cryptosporidium-sized particles on human subjects in a recreational water setting. AB - Cryptosporidium is a chlorine-resistant protozoan parasite responsible for the majority of waterborne disease outbreaks in recreational water venues in the USA. Swim diapers are commonly used by diaper-aged children participating in aquatic activities. This research was intended to evaluate disposable swim diapers for retaining 5-MUm diameter polystyrene microspheres, which were used as non infectious surrogates for Cryptosporidium oocysts. A hot tub recirculating water without a filter was used for this research. The microsphere concentration in the water was monitored at regular intervals following introduction of microspheres inside of a swim diaper while a human subject undertook normal swim/play activities. Microsphere concentrations in the bulk water showed that the majority (50-97%) of Cryptosporidium-sized particles were released from the swim diaper within 1 to 5 min regardless of the swim diaper type or configuration. After only 10 min of play, 77-100% of the microspheres had been released from all swim diapers tested. This research suggests that the swim diapers commonly used by diaper-aged children in swimming pools and other aquatic activities are of limited value in retaining Cryptosporidium-sized particles. Improved swim diaper solutions are necessary to efficiently retain pathogens and effectively safeguard public health in recreational water venues. PMID- 22048426 TI - Comparison of indicator bacteria inactivation by the ultraviolet and the ultraviolet/hydrogen peroxide disinfection processes in humic waters. AB - The aim of the present study was to evaluate responses of potential indicator bacteria (i.e. Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis) to the ultraviolet (UV) radiation and the UV/hydrogen peroxide (H2O2) disinfection processes of surface waters with different qualities in terms of humic content. The UV and the UV/H2O2 processes were applied to waters containing various concentrations of fulvic acid in order to inactivate E. coli, P. aeruginosa and B. subtilis spores. Three fulvic acid (0, 2 and 6 mg l(-1)) and four H2O2 (0, 10, 25 and 50 mg l(-1)) concentrations were used. Results showed that the k values of E. coli, P. aeruginosa and B. subtilis spores varied between 2.22 and 4.00, 1.73 and 3.58, and 1.40 and 1.86, respectively, in all test conditions. The sensitivity of the test organisms followed a decreasing order of E. coli > P. aeruginosa > B. subtilis. Results of the study indicated that the blocking effect of fulvic acid for the UV light was diminished by using H2O2 in combination with the UV radiation. Findings of the present study strongly suggested that the UV/H2O2 process was significantly effective on the inactivation of E. coli and P. aeruginosa in humic waters, whereas it induced little or no apparent contribution to the disinfection efficiency of B. subtilis spores. PMID- 22048427 TI - Virulence genes of Aeromonas isolates, bacterial endotoxins and cyanobacterial toxins from recreational water samples associated with human health symptoms. AB - Exposure to cyanobacterial water blooms has been associated with various kinds of adverse health effects. In addition to cyanobacteria and their toxins, the bacteria associated with cyanobacteria could also be the etiological agents. We isolated Aeromonas strains (n = 176) from water samples (n = 38) taken from sites where cyanobacteria were suspected to have caused human health symptoms, of which fever and gastrointestinal symptoms were the most common. The isolates were screened by PCR for six virulence gene types (12 genes). The majority (90%) of the strains contained at least one of the virulence genes. Most common amplification products were those of genes (act/aerA/hlyA) that encode cytotoxic enterotoxin and haemolytic products. The genes encoding cytotonic enterotoxins (ast and alt), phospholipase (lip/pla/lipH3/alp-1), elastase (ahyB) and flagellin subunits (flaA/flaB) were also present in 5-37% of the Aeromonas strains. Analysed toxins (cyanobacterial hepatotoxins and neurotoxins, and bacterial endotoxins) were not detectable or were present in only low concentrations in the majority of the samples. The results indicated that the toxins were unlikely to be the main cause of the reported adverse health effects, whereas more attention should be paid to bacteria associated with cyanobacteria as a source of health effects. PMID- 22048428 TI - An estimate of the cost of acute health effects from food- and water-borne marine pathogens and toxins in the USA. AB - Large and growing segments of the United States population consume seafood or engage in marine recreation. These activities provide significant benefits but also bring risk of exposure to marine-borne illness. To manage these risks, it is important to understand the incidence and cost of marine-borne disease. We review the literature and surveillance/monitoring data to determine the annual incidence of disease and health consequences due to marine-borne pathogens from seafood consumption and beach recreation in the USA. Using this data, we employ a cost-of illness model to estimate economic impacts. Our results suggest that health consequences due to marine-borne pathogens in the USA have annual costs on the order of US$900 million. This includes US$350 million due to pathogens and marine toxins specifically identified as causing food-borne disease, an estimated US$300 million due to seafood-borne disease with unknown etiology, US$30 million from direct exposure to the Vibrio species, and US$300 million due to gastrointestinal illness from beach recreation. Although there is considerable uncertainty about the degree of underreporting of certain pathogen-specific acute marine-related illnesses, the conservative assumptions we have used in constructing our estimate suggest that it should be considered a lower bound on true costs. PMID- 22048429 TI - Culture-based indicators of fecal contamination and molecular microbial indicators rarely correlate with Campylobacter spp. in recreational waters. AB - Campylobacter spp. are the leading cause of gastroenteritis worldwide. Most human infections result from contaminated food; however, infections are also caused by recreational waterway contamination. Campylobacter culture is technically challenging and enumeration by culture-based methods is onerous. Thus, we employed qPCR to quantify Campylobacter spp. in fresh- and marine-water samples, raw sewage and animal feces. Multiplex PCR determined whether Campylobacter jejuni or C. coli, most commonly associated with human disease, were present in qPCR-positive samples. Campylobacters were detected in raw sewage, and in feces of all avian and mammalian species tested. Campylobacter-positive concentrations ranged from 68 to 2.3 * 106 cells per 500 mL. Although C. jejuni and C. coli were rare in waterways, they were prevalent in sewage and feces. Campylobacter specific qPCR screening of environmental waters did not correlate with the regulatory EPA method 1600 (Enterococcus culture), nor with culture-independent, molecular-based microbial source tracking indicators, such as human polyomavirus, human Bacteroidales and Methanobrevibacter smithii. Our results suggest that neither the standard EPA method nor the newly proposed culture-independent methods are appropriate surrogates for Campylobacter contamination in water. Thus, assays for specific pathogens may be necessary to protect human health, especially in waters that are contaminated with sewage and animal feces. PMID- 22048430 TI - Hand-pumps as reservoirs for microbial contamination of well water. AB - The retention and release of total coliforms and Escherichia coli was investigated in hand-pumps removed from tubewells tapping a faecally contaminated aquifer in Matlab, Bangladesh, and from a new hand-pump deliberately spiked with E. coli. All hand-pumps were connected to reservoirs of sterile water and flushed. Faecal coliforms were observed in the discharge from all three of the previously used hand-pumps, at concentrations comparable to levels measured in discharge when they were attached to the tubewells. During daily flushing of one of the previously used hand-pumps, the concentration of total coliforms in the discharge remained relatively constant (approximately 103 MPN/100 mL). Concentrations of E. coli in the pump discharge declined over time, but E. coli was still detectable up to 29 days after the start of flushing. In the deliberately spiked hand-pump, E. coli was observed in the discharge over 125 days (t50 = 8 days) and found to attach preferentially to elastomeric materials within the hand-pump. Attempts to disinfect both the village and new hand-pumps using shock chlorination were shown to be unsuccessful. These results demonstrate that hand-pumps can act as persistent reservoirs for microbial indicator bacteria. This could potentially influence drinking water quality and bias testing of water quality. PMID- 22048431 TI - New USEPA water quality criteria by 2012: GOMA concerns and recommendations. AB - The Gulf of Mexico Alliance (GOMA) was tasked by the five Gulf State Governors to identify major issues affecting the Gulf of Mexico (GoM) and to set priorities for ameliorating these problems. One priority identified by GOMA is the need to improve detection methods for water quality indicators, pathogens and microbial source tracking. The United States Environmental Protection Agency (USEPA) is tasked with revising water quality criteria by 2012; however, the locations traditionally studied by the USEPA are not representative of the GoM and this has raised concern about whether or not the new criteria will be appropriate. This paper outlines a number of concerns, including deadlines associated with the USEPA Consent Decree, which may prevent inclusion of research needed to produce a well-developed set of methods and criteria appropriate for all regulated waters. GOMA makes several recommendations including ensuring that criteria formulation use data that include GoM-specific conditions (e.g. lower bather density, nonpoint sources), that rapid-testing methods be feasible and adequately controlled, and that USEPA maintains investments in water quality research once the new criteria are promulgated in order to assure that outstanding scientific questions are addressed and that scientifically defensible criteria are achieved for the GoM and other regulated waterbodies. PMID- 22048432 TI - Spatial variation of waterborne Escherichia coli - implications for routine water quality monitoring. AB - Escherichia coli are often used as faecal indicator bacteria (FIB) to provide a measure of microbial pollution in recreational and shellfish harvesting waters. However, although model forecasts for predicting the concentrations of FIB in surface waters are becoming more robust, they suffer from an inconsistency in quantification methods and an understanding of the spatial variation of FIB within a water course. The aim of this study was to investigate the transverse spatial variation in E. coli numbers (as an indicator of faecal pollution) across the estuary of the River Conwy, UK. Water samples were collected from four transverse transects across the estuary. Spatial variation of E. coli was significantly different from one side of the river to the other, although was not correlated with depth or the physiochemical properties of the water. Subsequently, microbial water quality classifications on the two opposite banks suggested very different levels of pollution coming down the river. This work has shown that the side of the river that routine water monitoring samples are taken from can make a significant difference to the classification of microbial water quality. This has important implications for sampling strategies and the use of microbial source tracking (MST) techniques. PMID- 22048433 TI - Microbiological assessment of private drinking water supplies in Co. Cork, Ireland. AB - The microbiological quality of 75 private drinking water supply boreholes in Co. Cork, Ireland was assessed in order to determine the incidence of contamination and the potential pathways of such contamination. Microbiological analysis was carried out using the membrane filtration technique for the recovery of thermotolerant (faecal) coliforms. The sanitary protection of the supplies was evaluated by means of systematic inspections and subsequent qualitative sanitary risk assessment. Almost a quarter of all supplies investigated (24%, n = 18) was found positive for thermotolerant coliforms. Weather conditions had a significant impact on microbiological water quality, increasing both contamination incidence and gross contamination frequency. Over half of the supplies had nine or more sanitary hazards and most had rudimentary sanitary protection measures at the head of the borehole. These low sanitary protection measures suggest that boreholes can pose a significant hazard to valuable groundwater resources by providing direct contamination routes. PMID- 22048434 TI - National surveillance capacity of water-related diseases in the WHO European region. AB - Water-related diseases continue to cause a high burden of mortality and morbidity in the countries of the European Region. Parties to the Protocol on Water and Health are committed to the sustainable use of water resources, the provision of safe drinking water and adequate sanitation to all people of the European Region, and to the reduction of the burden of water-related diseases. A specialized Task Force is implementing a work plan aimed at strengthening the capacity for water related disease surveillance, outbreak detection and contingency planning. Parties to the Protocol are obliged to set targets, and report on progress on water-related disease surveillance. The present paper aims to provide a baseline assessment of national capacities for water-related disease surveillance on the basis of the replies to a questionnaire. This was prepared in English and Russian and administered to 53 countries, 15 of which replied. The results confirm the heterogeneity in surveillance systems, the weakness of many countries to adequately survey emerging water-related diseases, and the need for specific remedial action. The findings of the exercise will form the basis for future action under the Protocol on Water and Health. PMID- 22048435 TI - Increased information on waterborne outbreaks through efficient notification system enforces actions towards safe drinking water. AB - In 1997, a compulsory notification system for waterborne outbreaks was introduced in Finland. The main aim of this notification is to obtain immediate information on suspected waterborne outbreaks in order to restrict and manage the outbreak promptly. During the past ten years, there have been 67 waterborne outbreaks in Finland, mainly associated with small groundwater supplies or private wells. The number of reported waterborne outbreaks has increased since the launch of the notification system indicating that the threshold limit of outbreak detection has most probably decreased. The number of cases of illness has fulfilled the national health target, which is below 0.01% of the population, but more action is still needed to ensure the production of safe drinking water under all circumstances. Ten years accumulation of knowledge on outbreaks has revealed that a compulsory notification system is an effective tool to gather information on waterborne outbreaks. The system has also increased awareness of possible problems related to the quality of drinking water. This article summarises management and legislative actions and policy measures taken so far in Finland to reduce the number of outbreaks and cases of illness related to them. PMID- 22048436 TI - Water supply services for Africa's urban poor: the role of resale. AB - In sub-Saharan Africa only 35% of the urban population has access to a piped water connection on their premises. The majority of households obtain water from public standpipes or from neighbors who are connected to the municipal network. Water resale is often prohibited, however, because of concerns about affordability and risks to public health. Using data collected from 1,377 households in Maputo, Mozambique, we compare the microbiological quality, as well as the time and money costs of water supply from individual house connections, public standpipes, and water obtained from neighbors. Households with their own water connections have better service across virtually all indicators measured, and express greater satisfaction with their service, as compared with those using other water sources. Households purchasing water from their neighbors pay lower time and money costs per liter of water, on average, as compared with those using standpipes. Resale competes favorably with standpipes along a number of service quality dimensions; however, after controlling for water supply characteristics, households purchasing water from neighbors are significantly less likely to be satisfied with their water service as compared with those using standpipes. PMID- 22048437 TI - Occurrence of Aeromonas spp. in a random sample of drinking water distribution systems in the USA. AB - Aeromonads are aquatic bacteria found in drinking water supplies worldwide. Some species, such as Aeromonas hydrophila, can cause disease in humans. For this survey, 293 United States public water systems were selected using random sampling, stratified by water source and system type. Water samples were collected during one year from three sites (six samples per site) in each system. Temperature, pH, turbidity, total and free chlorine were measured using standard methods. Aeromonads were detected in 130 of 5,042 valid samples (2.6%) from 42 (14.3%) systems using the ampicillin-dextrin agar with vancomycin culture method with oxidase, trehalose and indole confirmation tests. Concentrations of aeromonads in positive samples were 0.2 to 880 (median 1.6) colony-forming units (CFU) per 100 mL. Adjusted odds ratios of Aeromonas detection were 1.6 (95% confidence limits 1.0, 2.5) during the summer season, 3.3 (1.8, 6.2) for turbidity above 0.5 nephelometric units and 9.1 (3.5, 24) at 0 mg/L compared with 0.25 mg/L total chlorine. Geographic region, system size and type of water source were not significant predictors of Aeromonas detection in multivariate regression analysis. The results of this survey demonstrate the importance of maintaining adequate residual chlorine and low turbidity for preventing drinking water contamination with aeromonads. PMID- 22048438 TI - Virus contamination from operation and maintenance events in small drinking water distribution systems. AB - We tested the association of common events in drinking water distribution systems with contamination of household tap water with human enteric viruses. Viruses were enumerated by qPCR in the tap water of 14 municipal systems that use non disinfected groundwater. Ultraviolet disinfection was installed at all active wellheads to reduce virus contributions from groundwater to the distribution systems. As no residual disinfectant was added to the water, any increase in virus levels measured downstream at household taps would be indicative of distribution system intrusions. Utility operators reported events through written questionnaires. Virus outcome measures were related to distribution system events using binomial and gamma regression. Virus concentrations were elevated in the wells, reduced or eliminated by ultraviolet disinfection, and elevated again in distribution systems, showing that viruses were, indeed, directly entering the systems. Pipe installation was significantly associated with higher virus levels, whereas hydrant flushing was significantly associated with lower virus levels. Weak positive associations were observed for water tower maintenance, valve exercising, and cutting open a water main. Coliform bacteria detections from routine monitoring were not associated with viruses. Understanding when distribution systems are most vulnerable to virus contamination, and taking precautionary measures, will ensure delivery of safe drinking water. PMID- 22048441 TI - Direct correlation between regional systolic function and regional washout rate of 99mTc-sestamibi in patients with idiopathic dilated cardiomyopathy. AB - OBJECTIVE: Although a higher washout of 99mTc-sestamibi (MIBI) from the ischemic myocardium was reported, little is known about it in idiopathic, nonischemic dilated cardiomyopathy (DCM). Using a quantitative electrocardiographic-gated single-photon emission computed tomography strategy, regional myocardial function may be obtained in conjunction with regional tracer perfusion. The aim of this study was to investigate the significance of regional washout of MIBI compared with regional systolic function in patients with DCM. METHODS: Rest quantitative electrocardiographic-gated single-photon emission computed tomography was performed in 20 patients with DCM who had no significant coronary stenosis on coronary angiogram and in five normal volunteers. single-photon emission computed tomography imaging was observed at 30 min and 4 h after 740 MBq of MIBI injection, and the regional washout rate (WR) was calculated using a 20-segment model. RESULTS: The mean global ejection fraction was 28.2 +/- 12.4% and the mean end-diastolic volume was 177 +/- 78 ml. The myocardial segments were divided into three groups on the basis of the mean WR of normal volunteers: group A (n=164): WR >= 25.4% (=mean+SD); group B (n=138): 19.6% <= WR < 25.4%; group C (n=98): WR<19.6% (=mean-SD). The regional wall thickening of group A segments was significantly less than that of the other groups (11.6 +/- 0.7 vs. 14.0 +/- 0.9 and 14.9 +/- 0.7%, respectively, P<0.05). The global left ventricular ejection fraction showed significant negative correlation to the extent of group A segments per patient (R=-0.65, P<0.005), indicating that higher washout was the result of decreased systolic function in DCM hearts. CONCLUSION: Regional higher WR of MIBI may indicate a significant marker for myocardial damage in asymptomatic to mildly symptomatic patients with DCM. PMID- 22048440 TI - Plasma leptin and neuropeptide Y concentrations in patients with rheumatoid arthritis treated with infliximab, a TNF-alpha antagonist. AB - TNF-alpha is one of the key proinflammatory cytokines in pathogenesis of rheumatoid arthritis (RA). TNF-alpha was also found to enhance synthesis of leptin. Leptin is mainly adipocyte-derived hormone controlling appetite and energy expenditure. It acts through inhibition of neuropeptide Y secretion. It is possible that TNF-alpha-induced leptin secretion contributes to body mass reduction in patients with RA. The study was designed to determine the influence of inactivation of the TNF-alpha with infliximab on plasma leptin and neuropeptide Y concentrations in patients with RA. Sixteen female patients with RA treated with infliximab and 16 healthy women were investigated. Plasma leptin and neuropeptide Y concentrations were determined before, during and after 1 year management of the patients with infliximab and were compared with body mass index and body fatty and lean mass. There was no difference in plasma leptin concentration between the rheumatoid patients before therapy and the controls (15.6 +/- 1.85 and 14.5 +/- 2.15 ng/ml, respectively). Neuropeptide Y concentration was higher in the patients than in the controls (54.5 +/- 3.96 and 24.8 +/- 2.80 pmol/l, respectively). Treatment with infliximab resulted in enhancement in leptin concentration (18.5 +/- 2.34 ng/ml) and a slight increase in neuropeptide Y concentration (58.7 +/- 4.66 pmol/l). Physiological relationship between leptin and body mass was shown in the patients and was not altered during the treatment. There was no significant correlation between the disease activity and plasma leptin or neuropeptide Y concentrations. PMID- 22048442 TI - A randomised controlled pilot trial to evaluate and optimize the use of anti platelet agents in the perioperative management in patients undergoing general and abdominal surgery--the APAP trial (ISRCTN45810007). AB - PURPOSE: Surgeons are increasingly confronted by patients on long-term low-dose acetylsalicylic acid (ASA). However, owing to a lack of evidence-based data, a widely accepted consensus on the perioperative management of these patients in the setting of non-cardiac surgery has not yet been reached. Primary objective was to evaluate the safety of continuous versus discontinuous use of ASA in the perioperative period in elective general or abdominal surgery. METHODS: Fifty-two patients undergoing elective cholecystectomy, inguinal hernia repair or colonic/colorectal surgery were recruited to this pilot study. According to cardiological evaluation, non-high-risk patients who were on long-term treatment with low-dose ASA were eligible for inclusion. Patients were allocated randomly to continuous use of ASA or discontinuation of ASA intake for 5 days before until 5 days after surgery. The primary outcome was the incidence of major haemorrhagic and thromboembolic complications within 30 days after surgery. RESULTS: A total of 26 patients were allocated to each study group. One patient (3.8%) in the ASA continuation group required re-operation due to post-operative haemorrhage. In neither study group, further bleeding complications occurred. No clinically apparent thromboembolic events were reported in the ASA continuation and the ASA discontinuation group. Furthermore, there were no significant differences between both study groups in the secondary endpoints. CONCLUSIONS: Perioperative intake of ASA does not seem to influence the incidence of severe bleeding in non-high risk patients undergoing elective general or abdominal surgery. Further, adequately powered trials are required to confirm the findings of this study. PMID- 22048443 TI - [The AVRO study]. PMID- 22048444 TI - [Preparticipation electrocardiographic screening for the prevention of sudden death in sports medicine]. AB - Both the American Heart Association and the European Society of Cardiology consensus panel recommendations agree that cardiovascular screening for young competitive athletes is justifiable and compelling on ethical, legal, and medical grounds. However, there is a considerable discordance in the consensus guidelines on the pre-participation screening protocols used among European and US cardiologists/sports medicine physicians, with and without 12-lead electrocardiogram (ECG). In 1982 a nationwide program of pre-participation screening including ECG was launched in Italy. The aim of this article is to examine whether this long-running screening program should be considered a valid and advisable public health strategy. The analysis of data coming from the Italian experience indicates that ECG screening has provided adequate sensitivity and specificity for detection of potentially lethal cardiomyopathy or arrhythmias and has led to substantial reduction of mortality of young competitive athletes by approximately 90%. Screening has been feasible thanks to the Italian Health System, which is developed in terms of healthcare and prevention services, and because of the limited costs of cardiovascular evaluation in the setting of a mass program. The available scientific evidence suggests to adopt a screening protocol including ECG, which is the only screening tool proved to be effective. This article will also address the available data and criticisms concerning the screening program to prevent sudden cardiac death of middle-aged/senior athletes engaged in leisure-time sports activity. PMID- 22048445 TI - [Management of hypercholesterolemia in children: needs and concerns]. AB - In childhood, cholesterol values are closely related to the genetic heritage of the young patient. Among familial hypercholesterolemia, it is essential to identify the monogenic and multigenic forms. In monogenic forms, heterozygotes respond poorly or partially to changes in diet and lifestyle, making pharmacological therapy necessary; in homozygote patients plasmapheresis is required, and liver transplantation is the only intervention that can impact permanently on the development of cardiovascular lesions in adulthood. Conversely, multigenic forms or familial hypercholesterolemia secondary to other diseases respond to changes in diet and lifestyle as well as to pharmacological treatment. It remains unclear how early pharmacological intervention should be implemented. In particular, the presence in children of typical histological lesions of athero- sclerosis and their interaction with cardiovascular disease in adulthood justify a prompt, although cautious, intervention. In fact, cholesterol is necessary for normal development of the organism, provided that percentile values are in the normal range according to age and sex. Two methods of intervention are identified: a population strategy that should be implemented on a large scale for advice about diet and optimal level of physical activity; and an individual strategy, in which diet advice should be followed by pharmacological treatment. Pharmacological therapy may be administered even in children over the age of 8-10 years, if necessary. In younger patients, therapeutic interventions should be restricted to children with LDL cholesterol levels >500 mg/dl. Although statins have only been studied in populations affected by severe familial hypercholesterolemia in the short term, they seem to be the most effective agents in children owing to their efficacy and limited side effects. PMID- 22048446 TI - [Results and complications of permanent pacing in pediatric patients with congenital or acquired atrioventricular block]. AB - BACKGROUND: Currently there is no evidence to prefer an endocardial or epicardial approach for pacing in pediatric patients. This analysis was aimed at defining the complications of pacemaker implantation in a pediatric population with atrioventricular block according to a strategy of choosing an epicardial system for patients <10 kg and an endocardial system for patients >10 kg. METHODS: This is a retrospective study performed on 27 patients, with and without congenital heart disease, implanted with a permanent pacemaker because of idiopathic or acquired atrioventricular block at our Pediatric Cardiology and Cardiac Surgery Unit of S. Orsola-Malpighi Hospital in Bologna (Italy) between 1981 and 2010. Patients were divided into two groups: 70% of the population (group A) was implanted with an epicardial system, 30% (group B) with an endocardial system. RESULTS: After a mean follow-up of 14 years (17 +/- 8 years for group A, 7 +/- 5 years for group B), the most frequent complications were lead failure (44%) and infection (18%). Both were more common in the epicardial system group: lead failure rate 53% in group A vs 25% in group B (p=0.0001); infection rate 26% in group A vs 0% in group B (p=0.0001); rate of system revision or implantation of a new electrode 42% in group A vs 12% in group B (p=0.0001). CONCLUSIONS: The present study demonstrates a high complication rate in patients undergoing an epicardial pacing system implantation. However, in patients <10 kg the epicardial system allows subclavian venous access protection for endocardial system implantation after somatic growth, avoiding high-risk procedures of system revision or lead extraction and subclavian vein occlusion in the long term. PMID- 22048447 TI - [Undesired left ventricular pacing]. PMID- 22048449 TI - Dipolar origin of water etching of amino acid surfaces. AB - The etching induced by water on hydrophobic (001) surfaces of enantiomeric L-, D- and racemic DL-valine crystals has been characterized by means of atomic force microscopy (AFM) at ambient conditions. Well-defined chiral parallelepipedic shallow patterns, one bilayer deep, are observed for the enantiomeric crystals with sides (steps) oriented along low index crystallographic directions. Hence, chirality can be readily identified by visual inspection of an AFM image after etching. The formation of such regular patterns can be rationalized using basic concepts of electrical dipolar interactions. The key factor that determines the relative etching rate for each step and thus defines the shape of the etching patterns is the orientation of the molecular dipoles with respect to the step edge. The simplicity of the approach allows the prediction of the effect of water etching on other amino acid crystals as well as the effect of the interaction of water with amino acid molecules forming part of more complex structures. PMID- 22048448 TI - [Catheter ablation of atrial fibrillation: Health Technology Assessment Report from the Italian Association of Arrhythmology and Cardiac Pacing (AIAC)]. AB - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and significantly impact patients' quality of life, morbidity and mortality. The number of affected patients is expected to increase as well as the costs associated with AF management, mainly driven by hospitalizations. Over the last decade, catheter ablation techniques targeting pulmonary vein isolation have demonstrated to be effective in treating AF and preventing AF recurrence. This Health Technology Assessment report of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC) aims to define the current role of catheter ablation of AF in terms of effectiveness, efficiency and appropriateness. On the basis of an extensive review of the available literature, this report provides (i) an overview of the epidemiology, clinical impact and socio-economic burden of AF; (ii) an evaluation of therapeutic options other than catheter ablation of AF; and (iii) a detailed presentation of clinical outcomes and cost-benefit ratio associated with catheter ablation. The costs of catheter ablation of AF in Italy were obtained using a bottom-up analysis of a resource utilization survey of 52 hospitals that were considered a representative sample, including 4 Centers that contributed with additional unit cost information in a separate questionnaire. An analysis of budget impact was also performed to evaluate the impact of ablation on the management costs of AF. Results of this analysis show that (1) catheter ablation is effective, safe and superior to antiarrhythmic drug therapy in maintaining sinus rhythm; (2) the cost of an ablation procedure in Italy typically ranges from ?8868 to ?9455, though current reimbursement remains insufficient, covering only about 60% of the costs; (3) the costs of follow-up are modest (about 8% of total costs); (4) assuming an adjustment of reimbursement to the real cost of an ablation procedure and a 5-10% increase in the annual rate of ablation procedures, after approximately 5-6 years this would result in significant incremental savings for the Italian Healthcare System. In conclusion, catheter ablation of AF is a cost-effective procedure that is inadequately reimbursed in Italy. Insufficient reimbursement may serve as disincentive to perform AF ablation, thereby limiting patient access to this treatment. Considering the healthcare system perspective, higher initial costs for ablation procedures in the short term may be offset by cost savings mainly associated with decreased hospitalizations over time. PMID- 22048450 TI - [Nutrition following trauma]. PMID- 22048451 TI - [Nutritional management of severely injured patients : Treatment between guidelines and reality]. AB - Severe trauma triggers endocrine and inflammatory responses, leading to hyperglycaemia, insulin resistance and protein catabolism. Pharmacological and nutritional interventions cannot counteract these metabolic disturbances. However, adequate supply of energy and proteins may reduce excessive catabolism.Available guidelines recommend early use of enteral nutrition with energetic supply of about 25 kcal/kg and additional protein supply of 1.5 g/kg/day. These aims will be missed frequently by solely providing enteral nutrition in severely injured patients. Early supplemental parenteral nutrition should be used in these cases. Concomitantly, gastric paresis and paralytic ileus hampering enteral nutrition should be treated by propulsive and prokinetic drugs and by use of duodenal or jejunal site of application in selected cases.Euphoric hopes linked with intensified insulin therapy (IIT), targeting blood glucose levels <110 mg/dl in intensive care patients, had to be widely abandoned in recent years. The goal for blood glucose levels should be set at 180 mg/dl as the upper limit according to current knowledge, which promises to optimize the balance between efficacy and safety. PMID- 22048452 TI - TIM polymorphisms--genetics and function. AB - The transmembrane immunoglobulin and mucin domain (TIM) family was identified more than a decade ago. Although the founding member of the family was first described in a rat model of ischemia-reperfusion injury, much of the recent interest in the TIM family members has focused on their potential roles in immunity. There are now a large number of genetic studies that have investigated the possible association of various TIM1 and TIM3 polymorphisms with different diseases. Here, we review this body of literature, and highlight some of the most interesting studies. PMID- 22048453 TI - Variations in the heme oxygenase-1 microsatellite polymorphism are associated with plasma CD14 and viral load in HIV-infected African-Americans. AB - Heme oxygenase-1 (HO-1) is an anti-inflammatory enzyme that maintains homeostasis during cellular stress. Given previous findings that shorter length variants of a HO-1 promoter region GT(n) microsatellite polymorphism are associated with increased HO-1 expression in cell lines, we hypothesized that shorter variants would also be associated with increased levels of HO-1 expression, less inflammation and lower levels of inflammation-associated viral replication in human immunodeficiency virus (HIV)-infected subjects. Healthy donors (n = 20) with shorter GT(n) repeats had higher HO-1 mRNA transcript in peripheral blood mononuclear cells stimulated with lipopolysaccharide (r = -0.38, P = 0.05). The presence of fewer GT(n) repeats in subjects with untreated HIV disease was associated with higher HO-1 mRNA levels in peripheral blood (r = -0.41, P = 0.02); similar observations were made in CD14(+) monocytes from antiretroviral treated subjects (r = -0.36, P = 0.04). In African-Americans, but not Caucasians, greater GT(n) repeats were correlated with higher soluble CD14 levels during highly active antiretroviral therapy (r = 0.38, P = 0.007) as well as higher mean viral load off-therapy (r = 0.24, P = 0.04). These data demonstrate that the HO-1 GT(n) microsatellite polymorphism is associated with higher levels of HO-1 expression and that this pathway may have important effects on the association between inflammation and HIV replication. PMID- 22048454 TI - Molecular mechanisms underlying the regulation and functional plasticity of FOXP3(+) regulatory T cells. AB - CD4(+) CD25(+) regulatory T (Treg) cells engage in the maintenance of immunological self-tolerance and homeostasis by limiting aberrant or excessive inflammation. The transcription factor forkhead box P3 (FOXP3) is critical for the development and function of Treg cells. The differentiation of the Treg cell lineage is not terminal, as developmental and functional plasticity occur through the sensing of inflammatory signals in the periphery. Here, we review the recent progress in our understanding of the molecular mechanisms underlying the regulation and functional plasticity of CD4(+) CD25(+) FOXP3(+) Treg cells, through the perturbation of FOXP3 and its complex at a transcriptional, translational and post-translational level. PMID- 22048455 TI - A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of the IL10 and IL1R2 promoters is associated with disease activity. AB - The etiology of systemic lupus erythematosus (SLE) involves a complex interaction of genetic and environmental factors. Investigations have shown that environmentally driven epigenetic changes contribute to the etiology of SLE. Here, we hypothesize that aberrant DNA methylation may contribute to the activation of the immune machinery and trigger lupus disease activity. A whole genome methylation array was applied to investigate the DNA methylation changes between 12 pairs of active SLE patients and healthy controls. The results were further confirmed in 66 SLE patients, 102 healthy controls. The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (age-adjusted odds ratios, 64.2 and 16.9, respectively, P<0.0001). There was a trend toward SLE patients having hypomethylated IL10 and IL1R2 genes accompanied by greater disease activity. We observed that the methylation degree of IL10 and IL1R2 genes were reduced in the rheumatoid arthritis (RA) patients as well but the hypomethylation change was more significant in IL1R2 genes than in the IL10 genes in RA patients. This study demonstrated that DNA hypomethylation might be associated with SLE. Hypomethylated IL10 and IL1R2 genes may provide potential epigenetic markers as clinical predictors for autoimmune diseases. PMID- 22048456 TI - Synovial expression of Th17-related and cancer-associated genes is regulated by the arthritis severity locus Cia10. AB - We have previously identified Cia10 as an arthritis severity and articular damage quantitative trait locus. In this study, we used Illumina RatRef-12 microarrays to analyze the expression of 21,922 genes in synovial tissues from arthritis susceptible DA and arthritis-protected DA.ACI(Cia10) congenics with pristane induced arthritis. 310 genes had significantly different expression. The genes upregulated in DA, and reciprocally downregulated in DA.ACI(Cia10) included IL 11, Ccl12 and Cxcl10, as well as genes implicated in Th17 responses such as IL 17A, IL-6, Ccr6, Cxcr3 and Stat4. Suppressors of immune responses Tgfb and Vdr, and inhibitors of oxidative stress were upregulated in congenics. There was an over-representation of genes implicated in cancer and cancer-related phenotypes such as tumor growth and invasion among the differentially expressed genes. Cancer-favoring genes like Ctsd, Ikbke, and Kras were expressed in increased levels in DA, whereas inhibitors of cancer phenotypes such as Timp2, Reck and Tgfbr3 were increased in DA.ACI(Cia10). These results suggest that Cia10 may control arthritis severity, synovial hyperplasia and joint damage via the regulation of the expression of cancer-related genes, inflammatory mediators and Th17-related markers. These new findings have the potential to generate new targets for therapies aimed at reducing arthritis severity and joint damage in rheumatoid arthritis. PMID- 22048457 TI - SnO2 nanorod arrays: low temperature growth, surface modification and field emission properties. AB - SnO(2) nanorod arrays have been deposited on 4 inch SiO(2)/Si and Si wafers and stainless steel substrates by plasma-enhanced chemical vapor deposition without any high temperature treatment or additional catalysis. The SnO(2) nanorods grow up from seed nanocrystals along the [110] preferential direction by a self catalyzed vapor-solid growth mechanism. The surface of the SnO(2) nanorods was modified by ZnO, Pt and Ni nanocrystals. After surface modification, the field emission properties of the SnO(2) nanorod arrays are improved. The Ni nanocrystal with sharp tips and edges act as additional field emission sites to SnO(2) nanorods and thus the Ni/SnO(2)/SiO(2)/Si outperforms other samples due to the synergistic effects of good conductivity and hierarchical sharp apexes. The field enhancement factor of the Ni/SnO(2)/SiO(2)/Si increased around 3 times while the turn-on field of 8.0 V MUm(-1) is about one third of the SnO(2)/SiO(2)/Si device. PMID- 22048458 TI - Growth arrest and DNA-damage-inducible, beta (GADD45b)-mediated DNA demethylation in major psychosis. AB - Aberrant neocortical DNA methylation has been suggested to be a pathophysiological contributor to psychotic disorders. Recently, a growth arrest and DNA-damage-inducible, beta (GADD45b) protein-coordinated DNA demethylation pathway, utilizing cytidine deaminases and thymidine glycosylases, has been identified in the brain. We measured expression of several members of this pathway in parietal cortical samples from the Stanley Foundation Neuropathology Consortium (SFNC) cohort. We find an increase in GADD45b mRNA and protein in patients with psychosis. In immunohistochemistry experiments using samples from the Harvard Brain Tissue Resource Center, we report an increased number of GADD45b-stained cells in prefrontal cortical layers II, III, and V in psychotic patients. Brain-derived neurotrophic factor IX (BDNF IXabcd) was selected as a readout gene to determine the effects of GADD45b expression and promoter binding. We find that there is less GADD45b binding to the BDNF IXabcd promoter in psychotic subjects. Further, there is reduced BDNF IXabcd mRNA expression, and an increase in 5-methylcytosine and 5-hydroxymethylcytosine at its promoter. On the basis of these results, we conclude that GADD45b may be increased in psychosis compensatory to its inability to access gene promoter regions. PMID- 22048459 TI - Exogenous and endogenous cannabinoids suppress inhibitory neurotransmission in the human neocortex. AB - Activation of CB(1) receptors on axon terminals by exogenous cannabinoids (eg, Delta(9)-tetrahydrocannabinol) and by endogenous cannabinoids (endocannabinoids) released by postsynaptic neurons leads to presynaptic inhibition of neurotransmission. The aim of this study was to characterize the effect of cannabinoids on GABAergic synaptic transmission in the human neocortex. Brain slices were prepared from neocortical tissues surgically removed to eliminate epileptogenic foci. Spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) were recorded in putative pyramidal neurons using patch-clamp techniques. To enhance the activity of cannabinoid-sensitive presynaptic axons, muscarinic receptors were continuously stimulated by carbachol. The synthetic cannabinoid receptor agonist WIN55212-2 decreased the cumulative amplitude of sIPSCs. The CB(1) antagonist rimonabant prevented this effect, verifying the involvement of CB(1) receptors. WIN55212-2 decreased the frequency of miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin, but did not change their amplitude, indicating that the neurotransmission was inhibited presynaptically. Depolarization of postsynaptic pyramidal neurons induced a suppression of sIPSCs. As rimonabant prevented this suppression, it is very likely that it was due to endocannabinods acting on CB(1) receptors. This is the first demonstration that an exogenous cannabinoid inhibits synaptic transmission in the human neocortex and that endocannabinoids released by postsynaptic neurons suppress synaptic transmission in the human brain. Interferences of cannabinoid agonists and antagonists with synaptic transmission in the cortex may explain the cognitive and memory deficits elicited by these drugs. PMID- 22048460 TI - Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: a randomized double-blind placebo controlled trial. AB - The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the alpha4beta2 and full agonist at the alpha7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. In all, 120 clinically stable people with schizophrenia participated in randomized, double-blind, placebo-controlled 8-week trial. Antipsychotic and concomitant medication doses remained fixed throughout the study. Varenicline was titrated up to 1 mg twice daily for weeks 2-8. Neuropsychological, clinical, and safety assessments were administered at baseline and weeks 1, 2, 4, and 8. In the primary analyses of neurocognitive differences at week 8, no varenicline-placebo differences were significant. In secondary longitudinal analyses, varenicline improved compared with placebo on the Digital Symbol Substitution Test (p=0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p=0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p=0.008) and Stroop Interference (p=0.004) were reduced for varenicline compared with placebo, while there were no treatment differences in non-smokers. No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms. Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia. In some cases, effects of treatment varied between smokers and non-smokers. Further study is required to assess the functional significance of these changes. PMID- 22048461 TI - Effect of variation in diacylglycerol kinase eta (DGKH) gene on brain function in a cohort at familial risk of bipolar disorder. AB - Several lines of evidence indicate that the diacylglycerol kinase eta (DGKH) gene is implicated in the etiology of bipolar disorder (BD). However, the functional neural mechanisms of DGKH's risk association remain unknown. Therefore, we examined the effects of three haplotype-tagging risk variants in DGKH (single nucleotide polymorphisms rs9315885, rs1012053, and rs1170191) on brain activation using a verbal fluency functional magnetic resonance imaging task. The subject groups consisted of young individuals at high familial risk of BD (n=81) and a comparison group of healthy controls (n=75). Individuals were grouped based on risk haplotypes described in previous studies. There was a significant risk haplotype*group interaction in the left medial frontal gyrus (BA10, involving anterior cingulate BA32), left precuneus, and right parahippocampal gyrus. All regions demonstrated greater activation during the baseline condition than sentence completion. Individuals at high familial risk for BD homozygous for the DGKH risk haplotype demonstrated relatively greater activation (poor suppression) of these regions during the task vs the low-risk haplotype subjects. The reverse pattern was seen for the control subjects. These findings suggest that there are differential effects of the DGKH gene in healthy controls vs the bipolar high risk group, which manifests as a failure to disengage default-mode regions in those at familial risk carrying the risk haplotype. PMID- 22048462 TI - Mifepristone in the central nucleus of the amygdala reduces yohimbine stress induced reinstatement of ethanol-seeking. AB - Chronic ethanol exposure leads to dysregulation of the hypothalamic-pituitary adrenal axis, leading to changes in glucocorticoid release and function that have been proposed to maintain pathological alcohol consumption and increase vulnerability to relapse during abstinence. The objective of this study was to determine whether mifepristone, a glucocorticoid receptor antagonist, plays a role in ethanol self-administration and reinstatement. Male, Long-Evans rats were trained to self-administer either ethanol or sucrose in daily 30 min operant self administration sessions using a fixed ratio 3 schedule of reinforcement. Following establishment of stable baseline responding, we examined the effects of mifepristone on maintained responding and yohimbine-induced increases in responding for ethanol and sucrose. Lever responding was extinguished in separate groups of rats and animals were tested for yohimbine-induced reinstatement and corticosterone release. We also investigated the effects of local mifepristone infusions into the central amygdala (CeA) on yohimbine-induced reinstatement of ethanol- and sucrose-seeking. In addition, we infused mifepristone into the basolateral amygdala (BLA) in ethanol-seeking animals as an anatomical control. We show that both systemic and intra-CeA (but not BLA) mifepristone administration suppressed yohimbine-induced reinstatement of ethanol-seeking, while only systemic injections attenuated sucrose-seeking. In contrast, baseline consumption, yohimbine-induced increases in responding, and circulating CORT levels were unaffected. The data indicate that the CeA plays an important role in the effects of mifepristone on yohimbine-induced reinstatement of ethanol seeking. Mifepristone may be a valuable pharmacotherapeutic strategy for preventing relapse to alcohol use disorders and, as it is FDA approved, may be a candidate for clinical trials in the near future. PMID- 22048463 TI - Abnormal activity of the MAPK- and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia. AB - Recent evidence suggests that schizophrenia may result from alterations of integration of signaling mediated by multiple neurotransmitter systems. Abnormalities of associated intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. Proteins and phospho-proteins comprising mitogen activated protein kinase (MAPK) and 3'-5'-cyclic adenosine monophosphate (cAMP)-associated signaling pathways may be abnormally expressed in the anterior cingulate (ACC) and dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Using western blot analysis we examined proteins of the MAPK- and cAMP-associated pathways in these two brain regions. Postmortem samples were used from a well characterized collection of elderly patients with schizophrenia (ACC=36, DLPFC=35) and a comparison (ACC=33, DLPFC=31) group. Near-infrared intensity of IR-dye labeled secondary antisera bound to targeted proteins of the MAPK- and cAMP-associated signaling pathways was measured using LiCor Odyssey imaging system. We found decreased expression of Rap2, JNK1, JNK2, PSD-95, and decreased phosphorylation of JNK1/2 at T183/Y185 and PSD-95 at S295 in the ACC in schizophrenia. In the DLPFC, we found increased expression of Rack1, Fyn, Cdk5, and increased phosphorylation of PSD-95 at S295 and NR2B at Y1336. MAPK- and cAMP associated molecules constitute ubiquitous intracellular signaling pathways that integrate extracellular stimuli, modify receptor expression and function, and regulate cell survival and neuroplasticity. These data suggest abnormal activity of the MAPK- and cAMP-associated pathways in frontal cortical areas in schizophrenia. These alterations may underlie the hypothesized hypoglutamatergic function in this illness. Together with previous findings, these data suggest that abnormalities of intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. PMID- 22048464 TI - Modulation of fronto-cortical activity by modafinil: a functional imaging and fos study in the rat. AB - Modafinil (MOD) is a wake-promoting drug with pro-cognitive properties. Despite its increasing use, the neuronal substrates of MOD action remain elusive. In particular, animal studies have highlighted a putative role of diencephalic areas as primary neuronal substrate of MOD action, with inconsistent evidence of recruitment of fronto-cortical areas despite the established pro-cognitive effects of the drug. Moreover, most animal studies have employed doses of MOD of limited clinical relevance. We used pharmacological magnetic resonance imaging (phMRI) in the anesthetized rat to map the circuitry activated by a MOD dose producing clinically relevant plasma exposure, as here ascertained by pharmacokinetic measurements. We observed prominent and sustained activation of the prefrontal and cingulate cortex, together with weaker but significant activation of the somatosensory cortex, medial thalamic domains, hippocampus, ventral striatum and dorsal raphe. Correlation analysis of phMRI data highlighted enhanced connectivity within a neural network including dopamine projections from the ventral tegmental area to the nucleus accumbens. The pro-arousing effect of MOD was assessed using electroencephalographic recording under anesthetic conditions comparable to those used for phMRI, together with the corresponding Fos immunoreactivity distribution. MOD produced electroencephalogram desynchronization, resulting in reduced delta and increased theta frequency bands, and a pattern of Fos induction largely consistent with the phMRI study. Altogether, these findings show that clinically relevant MOD doses can robustly activate fronto-cortical areas involved in higher cognitive functions and a network of pro-arousing areas, which provide a plausible substrate for the wake promoting and pro-cognitive effects of the drug. PMID- 22048466 TI - Smoking cessation pharmacogenetics: analysis of varenicline and bupropion in placebo-controlled clinical trials. AB - Despite effective therapies for smoking cessation, most smokers find quitting difficult and most successful quitters relapse. Considerable evidence supports a genetic risk for nicotine dependence; however, less is known about the pharmacogenetics of smoking cessation. In the first pharmacogenetic investigation of the efficacy of varenicline and bupropion, we examined whether genes important in the pharmacodynamics and pharmacokinetics of these drugs and nicotine predict medication efficacy and adverse events. Subjects participated in randomized, double-blind, placebo-controlled smoking cessation clinical trials, comparing varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist, with bupropion, a norepinephrine/dopamine reuptake inhibitor, and placebo. Primary analysis included 1175 smokers of European ancestry, and 785 single nucleotide polymorphisms from 24 genes, representing 254 linkage disequilibrium (LD) bins (genes included nAChR subunits, additional varenicline-specific genes, and genes involved in nicotine or bupropion metabolism). For varenicline, continuous abstinence (weeks 9-12) was associated with multiple nAChR subunit genes (including CHRNB2, CHRNA5, and CHRNA4) (OR=1.76; 95% CI: 1.23-2.52) (p<0.005); for bupropion, abstinence was associated with CYP2B6 (OR=1.78; 95% CI: 1.27-2.50) (p<0.001). Incidence of nausea was associated with several nAChR subunit genes (OR=0.50; 95% CI: 0.36-0.70) (p<0.0001) and time to relapse after quitting was associated with HTR3B (HR=1.97; 95% CI: 1.45-2.68) (p<0.0001). These data provide evidence for multiple genetic loci contributing to smoking cessation and therapeutic response. Different loci are associated with varenicline vs bupropion response, suggesting that additional research may identify clinically useful markers to guide treatment decisions. PMID- 22048467 TI - Regional cortical thickness and subcortical volume changes are associated with cognitive impairments in the drug-naive patients with late-onset depression. AB - Previous studies have shown an association between late-onset depression (LOD) and cognitive impairment in older adults. However, the neural correlates of this relationship are not yet clear. The aim of this study was to investigate the differences in both cortical thickness and subcortical volumes between drug-naive LOD patients and healthy controls and explore the relationship between LOD and cognitive impairments. A total of 48 elderly, drug-naive patients with LOD and 47 group-matched healthy control subjects underwent 3T MRI scanning, and the cortical thickness was compared between the groups in multiple locations, across the continuous cortical surface. The subcortical volumes were also compared on a structure-by-structure basis. Subjects with LOD exhibited significantly decreased cortical thickness in the rostral anterior cingulate cortex, the medial orbitofrontal cortex, dorsolateral prefrontal cortex, the superior and middle temporal cortex, and the posterior cingulate cortex when compared with healthy subjects (all p<0.05, false discovery rate corrected). Reduced volumes of the right hippocampus was also observed in LOD patients when compared with healthy controls (p<0.001). There were significant correlations between memory functions and cortical thickness of medial temporal, isthmus cingulate, and precuneus (p<0.001). This study was the first study to explore the relationships between the cortical thickness/subcortical volumes and cognitive impairments of drug naive patients with LOD. These structural changes might explain the neurobiological mechanism of LOD as a risk factor of dementia. PMID- 22048465 TI - Cognitive training for impaired neural systems in neuropsychiatric illness. AB - Neuropsychiatric illnesses are associated with dysfunction in distributed prefrontal neural systems that underlie perception, cognition, social interactions, emotion regulation, and motivation. The high degree of learning dependent plasticity in these networks-combined with the availability of advanced computerized technology-suggests that we should be able to engineer very specific training programs that drive meaningful and enduring improvements in impaired neural systems relevant to neuropsychiatric illness. However, cognitive training approaches for mental and addictive disorders must take into account possible inherent limitations in the underlying brain 'learning machinery' due to pathophysiology, must grapple with the presence of complex overlearned maladaptive patterns of neural functioning, and must find a way to ally with developmental and psychosocial factors that influence response to illness and to treatment. In this review, we briefly examine the current state of knowledge from studies of cognitive remediation in psychiatry and we highlight open questions. We then present a systems neuroscience rationale for successful cognitive training for neuropsychiatric illnesses, one that emphasizes the distributed nature of neural assemblies that support cognitive and affective processing, as well as their plasticity. It is based on the notion that, during successful learning, the brain represents the relevant perceptual and cognitive/affective inputs and action outputs with disproportionately larger and more coordinated populations of neurons that are distributed (and that are interacting) across multiple levels of processing and throughout multiple brain regions. This approach allows us to address limitations found in earlier research and to introduce important principles for the design and evaluation of the next generation of cognitive training for impaired neural systems. We summarize work to date using such neuroscience-informed methods and indicate some of the exciting future directions of this field. PMID- 22048469 TI - Hypoxia inducible factor-1alpha contributes to UV radiation-induced inflammation, epidermal hyperplasia and immunosuppression in mice. AB - Hypoxia inducible factor-1alpha (HIF-1alpha), a ubiquitous inducible oxygen sensing transcription factor, promotes cell survival under hypoxic conditions, including the early pre-angiogenic period of tumorigenesis, and is known to contribute to many malignancies. However HIF-1alpha can also be activated by inflammatory mediators, and can activate inflammation-modulating proteins itself, including heme oxygenase-1 (HO-1) and the cytokine IL-6. Recently HIF-1alpha was reported to be induced by UVB (290-320 nm) radiation in cultured human keratinocytes, acting as a stress protein associated with the release of reactive oxygen species. In this in vivo murine study we demonstrate that HIF-1alpha protein is an early responder to UV radiation in the skin, and its activation can be attenuated by treating mice with its post-translational inhibitor, YC-1. Treatment with YC-1 following UV-irradiation of mice has revealed the involvement of HIF-1alpha in UV-induced inflammation, IL-6 production, and epidermal hyperplasia. In addition, upregulated cutaneous HIF-1alpha was found to be an important factor in the UV-suppression of T cell-mediated immunity, measured by contact hypersensitivity (CHS). The mechanism remains unclear, however it did not appear to involve the immunosuppressive cutaneous photoproduct cis-urocanic acid, but HIF-1alpha induction was inhibited by irradiation with photoimmune protective UVA (320-400 nm), implicating a negative correlation between the two stress proteins, HIF-1alpha and the photoimmune protective UVA responder HO-1. PMID- 22048468 TI - Conditioned response evoked by nicotine conditioned stimulus preferentially induces c-Fos expression in medial regions of caudate-putamen. AB - Nicotine has both unconditioned and conditioned stimulus properties. Conditioned stimulus properties of nicotine may contribute to the tenacity of nicotine addiction. The purpose of this experiment was to use neurohistochemical analysis of rapidly developing c-Fos protein to elucidate neurobiological loci involved in the processing of nicotine as an interoceptive conditioned stimulus (CS). Rats were injected (SC) in an intermixed fashion with saline or nicotine (16 sessions of each) and placed in conditioning chambers where they were given one of the three conditions depending on group assignment: (a) nicotine paired 100% of the time with intermittent access to sucrose (nicotine-CS condition), (b) nicotine and saline each paired 50% of the time with sucrose (chamber-CS condition), or (c) no sucrose US control (CS-alone condition). Rats in the nicotine-CS condition acquired the discrimination as evidenced by goal-tracking (ie, increased dipper entries before initial sucrose delivery) only on nicotine sessions. The chamber CS condition showed goal-tracking on all sessions; no goal-tracking was seen in the CS-alone condition. On the test day, rats in each condition were challenged with saline or nicotine and later assessed for c-Fos immunoreactivity. In concordance with previous reports, nicotine induced c-Fos expression in the majority of areas tested; however, learning-dependent expression was specific to dorsomedial and ventromedial regions of caudate-putamen (dmCPu, vmCPu). Only rats in the nicotine-CS condition, when challenged with nicotine, had higher c-Fos expression in the dmCPu and vmCPu. These results suggest that medial areas of CPu involved in excitatory conditioning with an appetitive nicotine CS. PMID- 22048470 TI - A soluble hybrid material combining carbon nanohorns and C60. AB - A soluble hybrid nanomaterial that combines fullerenes and carbon nanohorns (CNHs) has been prepared and fully characterized. Electrochemical investigations revealed that the CNHs modify the electron accepting ability of C(60) in the hybrid material. PMID- 22048471 TI - beta-Fe2O3 nanomaterials from an iron(II) diketonate-diamine complex: a study from molecular precursor to growth process. AB - Iron oxide is a key multi-functional material in many different fields of modern technology. The beta-Fe(2)O(3) cubic phase, one of the least studied Fe-O systems, was obtained by Chemical Vapor Deposition (CVD) using for the first time a Fe(II) beta-diketonate diamine complex, Fe(hfa)(2).TMEDA, as the molecular source (hfa = 1,1,1,5,5,5-hexafluoro-2,4-pentanedionate; TMEDA = N,N,N',N' tetramethylethylenediamine). The strong visible light absorption of beta Fe(2)O(3) deposits highlights their possible functional application in photocatalytic hydrogen production under solar light. A comprehensive investigation on the Fe(ii) complex, performed by a joint experimental theoretical approach, explains the molecular origin of its excellent thermal behaviour and reveals why this species is a successful precursor for the CVD of iron oxide nanostructures. PMID- 22048472 TI - 2011 Founders Award. Ralph H. Thomas. PMID- 22048473 TI - 2011 Distinguished Public Service Award. Genevieve Roessler. PMID- 22048474 TI - 2011 Elda E. Anderson Award. Sarah J. Roberts. PMID- 22048475 TI - 2011 H. Wade Patterson Memorial Award. Santosh Bhatt. PMID- 22048476 TI - 2011 Lutz Moritz Memorial Award. Jeremy Rogers. PMID- 22048477 TI - 2011 Geoffrey G. Eichholz Outstanding Science Teacher Award. Richard Cole. PMID- 22048479 TI - 2011 Health Physics Society Student Science Awards. Emily Beisett, Victoria Barnes, Tabitha Clifford, Gautam Kanumuru. PMID- 22048481 TI - 2011 Health Physics Society Honor Roll. Thomas M. Gerusky. PMID- 22048482 TI - 2011 Health Physics Honor Roll. Jim Johnson. PMID- 22048483 TI - 2011 American Academic of Health Physics National Service Award. Kyle R. Kleinhans. PMID- 22048484 TI - 2011 William A. McAdams Outstanding Service Award. Jerry W. Hiatt. PMID- 22048485 TI - Reliability of a new biokinetic model of zirconium in internal dosimetry: part I, parameter uncertainty analysis. AB - The reliability of biokinetic models is essential in internal dose assessments and radiation risk analysis for the public, occupational workers, and patients exposed to radionuclides. In this paper, a method for assessing the reliability of biokinetic models by means of uncertainty and sensitivity analysis was developed. The paper is divided into two parts. In the first part of the study published here, the uncertainty sources of the model parameters for zirconium (Zr), developed by the International Commission on Radiological Protection (ICRP), were identified and analyzed. Furthermore, the uncertainty of the biokinetic experimental measurement performed at the Helmholtz Zentrum Munchen German Research Center for Environmental Health (HMGU) for developing a new biokinetic model of Zr was analyzed according to the Guide to the Expression of Uncertainty in Measurement, published by the International Organization for Standardization. The confidence interval and distribution of model parameters of the ICRP and HMGU Zr biokinetic models were evaluated. As a result of computer biokinetic modelings, the mean, standard uncertainty, and confidence interval of model prediction calculated based on the model parameter uncertainty were presented and compared to the plasma clearance and urinary excretion measured after intravenous administration. It was shown that for the most important compartment, the plasma, the uncertainty evaluated for the HMGU model was much smaller than that for the ICRP model; that phenomenon was observed for other organs and tissues as well. The uncertainty of the integral of the radioactivity of Zr up to 50 y calculated by the HMGU model after ingestion by adult members of the public was shown to be smaller by a factor of two than that of the ICRP model. It was also shown that the distribution type of the model parameter strongly influences the model prediction, and the correlation of the model input parameters affects the model prediction to a certain extent depending on the strength of the correlation. In the case of model prediction, the qualitative comparison of the model predictions with the measured plasma and urinary data showed the HMGU model to be more reliable than the ICRP model; quantitatively, the uncertainty model prediction by the HMGU systemic biokinetic model is smaller than that of the ICRP model. The uncertainty information on the model parameters analyzed in this study was used in the second part of the paper regarding a sensitivity analysis of the Zr biokinetic models. PMID- 22048486 TI - Reliability of a new biokinetic model of zirconium in internal dosimetry: part II, parameter sensitivity analysis. AB - The reliability of biokinetic models is essential for the assessment of internal doses and a radiation risk analysis for the public and occupational workers exposed to radionuclides. In the present study, a method for assessing the reliability of biokinetic models by means of uncertainty and sensitivity analysis was developed. In the first part of the paper, the parameter uncertainty was analyzed for two biokinetic models of zirconium (Zr); one was reported by the International Commission on Radiological Protection (ICRP), and one was developed at the Helmholtz Zentrum Munchen-German Research Center for Environmental Health (HMGU). In the second part of the paper, the parameter uncertainties and distributions of the Zr biokinetic models evaluated in Part I are used as the model inputs for identifying the most influential parameters in the models. Furthermore, the most influential model parameter on the integral of the radioactivity of Zr over 50 y in source organs after ingestion was identified. The results of the systemic HMGU Zr model showed that over the first 10 d, the parameters of transfer rates between blood and other soft tissues have the largest influence on the content of Zr in the blood and the daily urinary excretion; however, after day 1,000, the transfer rate from bone to blood becomes dominant. For the retention in bone, the transfer rate from blood to bone surfaces has the most influence out to the endpoint of the simulation; the transfer rate from blood to the upper larger intestine contributes a lot in the later days; i.e., after day 300. The alimentary tract absorption factor (fA) influences mostly the integral of radioactivity of Zr in most source organs after ingestion. PMID- 22048487 TI - Comparison of methods of estimation of lifetime cancer risk due to chronic exposure to transuranics. AB - The cancer risk due to chronic transuranic intakes is properly calculated using an integration over multiple years of intake of the annual effective dose rates arising each year following an intake multiplied by age-dependent risk functions for the year during which the dose is actually received. Approximate computations of risk involving sums of the products of committed effective dose and the age dependent risk functions for each year of intake indicate the appropriateness of the committed effective dose as a surrogate quantity for risk when applied to different circumstances. The assumptions that all dose is received at the time of intake with committed effective dose and that risk is uniform over a range of ages both lead to a misuse of the available age-dependent risk functions and thus contribute to a divergence from the true risk associated with an intake over multiple years. Comparison of the correctly integrated risk functions with the approximations gives insights into how the current committed effective dose models used for regulatory purposes are not necessarily indicative of the risk for chronic intakes of radionuclides with long biological and radiological half lives. A summary and comparison of such computations for transuranic intakes was prepared for the ingestion of water and the inhalation of different particle sizes by both males and females. Risk results for committed effective dose consistently overestimated risks by approximately 100% for all transuranics for ingestion models and approximately 75% for all transuranics for Type M inhalation models considering age-dependent risk models. For constant risk as a function of age, the committed effective dose integration underestimated the actual risk situation by nearly 60% for ingestion and 50% for Type M inhalation during the first 20 y. PMID- 22048488 TI - Radiation background in a LaBr3(Ce) gamma-ray scintillation detector. AB - Gamma-ray spectral analyses with a 5-cm * 5-cm LaBr3(Ce) detector and a NaI(Tl) detector of the same size show that the LaBr3(Ce) has much better gamma-ray peak resolution and full-energy peak counting efficiency but worse detection sensitivity. The LaBr3(Ce) detector has relatively high intrinsic radiation background due to the naturally occurring La radioisotope in lanthanum. Although this La background is entirely below the energy of 1,500 keV, additional background is in the energy region between 1,500 keV and 2,750 keV. The manufacturer attributes this radiation to alpha particles emitted by the five short-lived progeny of an Ac impurity. Comparative values for peak resolution, full-energy peak counting efficiency, and detection sensitivity are reported for Am, Co, and Cs. Results of counting Cs sources at two activity levels demonstrate the impact of background on detection sensitivity. PMID- 22048489 TI - Historical development and evolution of EPRI's post-closure dose assessment of potential releases to the biosphere from the proposed HLW repository at Yucca Mountain. AB - This paper describes the development and evolution of the Electric Power Research Institute's (EPRI) post-closure dose assessment for potential releases of radionuclides from the proposed High Level Waste repository at Yucca Mountain. The starting point for this work was the 1995 publication of Technical Bases for Yucca Mountain Standards by the Commission on Geosciences, Environment and Resources of the National Research Council. This report proposed the development and application of an individual risk-based standard for releases from the repository to replace the existing one, which was based on radionuclide release limits. This in turn implied the development and application of methods to assess radiation doses to humans. Accordingly, EPRI produced a methodology for such dose assessment as part of its Total System Performance Assessment program for the proposed Yucca Mountain repository site. The methodology initially addressed releases via groundwater and then releases associated with extrusive igneous events. The methodology was updated and applied over the following years to take account of regulatory developments, changes in estimates of the source term to the biosphere, peer review through international model comparison exercises, new site generic data, and new data concerning conditions at the point of compliance in Amargosa Valley. The main outputs were Biosphere Dose Conversion Factors, which relate radionuclide levels in environmental media to the annual individual doses to a member of a hypothetical critical group and to the regulator-defined Reasonably Maximally Exposed Individual. Most recently, consideration has been given to uncertainty in the dose estimates based on a probabilistic analysis. The paper provides a perspective on the evolution of the dose assessments in response to the developments listed above. PMID- 22048490 TI - An improved model for prediction of resuspension. AB - A complete, historical dataset is presented of radionuclide resuspension-factors. These data span six orders of magnitude in time (ranging from 0.1 to 73,000 d), encompass more than 300 individual values, and combine observations from events on three continents. These data were then used to derive improved, empirical models that can be used to predict resuspension of trace materials after their deposit on the ground. Data-fitting techniques were used to derive models of various types and an estimate of uncertainty in model prediction. Two models were found to be suitable: a power law and the modified Anspaugh et al. model, which is a double exponential. Though statistically the power-law model provides the best metrics of fit, the modified Anspaugh model is deemed the more appropriate due to its better fit to data at early times and its ease of implementation in terms of closed analytical integrals. PMID- 22048491 TI - Mg ATP and antioxidants augment the radioprotective effect of surfactant copolymers. AB - Mediated by reactive oxygen species, the damaging effects of high-intensity ionizing irradiation on tissues are dose, frequency, oxygen concentration, and tissue property dependent. Intense ionizing irradiation exposure may cause rapid cellular necrosis by peroxidation of membrane lipids leading to membrane disruption. This leads to a loss of the transmembrane ionic gradients and a subsequent depletion of the cellular ATP store, followed by cellular generation of reactive oxygen species. When membrane disruption is extensive, acute cellular necrosis follows. Triblock copolymer surfactants, such as Poloxamer 188 (P188), are able to seal damaged rhabdomyocyte membranes, increasing post-irradiation viability. Separated rat rhabdomyocytes were exposed to 40 Gy (Co 1.5 Gy min) irradiation and treated at 20 min intervals with combination permutations of P188, N-acetylcysteine (NAC), and Mg-ATP. Cell viability at 18 and 48 h was determined using Calcein-AM and Ethidium Homodimer-1 staining. At 18 h after irradiation, the combined administration of P188, ATP, and NAC restored cell viability rates to near sham-exposed levels of 60%. At 48 h post-irradiation, cell viability dropped substantially to the 7-20% range, regardless of attempted intervention. Nevertheless, the combination of P188, ATP, and NAC more than doubled cell viability at the 48-h time point. Neither 8 kDa polyethylene glycol nor 10 kDa neutral dextran was as effective in enhancing cell viability. These results indicate that antioxidants and cellular energy substrates improve the efficacy of membrane-sealing copolymer surfactants in prolonging cellular viability following massive radiation exposure. PMID- 22048492 TI - Exposure to high-frequency electromagnetic fields (100 kHz-2 GHz) in Extremadura (Spain). AB - The last decade has seen a rapid increase in people's exposure to electromagnetic fields. This paper reports the measurements of radiofrequency (RF) total power densities and power density spectra in 35 towns of the region of Extremadura, Spain. The spectra were taken with three antennas covering frequencies from 100 kHz to 2.2 GHz. This frequency range includes AM/FM radio broadcasting, television, and cellular telephone signals. The power density data and transmitting antenna locations were stored in a geographic information system (GIS) as an aid in analyzing and interpreting the results. The results showed the power density levels to be below the reference level guidelines for human exposure and that the power densities are different for different frequency ranges and different size categories of towns. PMID- 22048493 TI - A novel phantom model for mouse tumor dose assessment under MV beams. AB - In order to determine a mouse's dose accurately and prior to engaging in live mouse radiobiological research, a tissue-equivalent tumor-bearing phantom mouse was constructed and bored to accommodate detectors. Comparisons were made among four different types of radiation detectors, each inserted into the mouse phantom for radiation measurement under a 6 MV linear accelerator beam. Dose detection response from a diode, thermoluminescent dosimeters, and metal-oxide semiconductor field-effect transistors were used and compared to that of a reference pinpoint ionization chamber. A computerized treatment planning system was also directly compared to the chamber. Each detector system demonstrated results similar to the dose computed by the treatment planning system, although some differences were noted. The average disagreement from an accelerator calibrated output dose prescription in the range of 200-400 cGy was -0.4% +/- 0.5 sigma for the diode, -2.4% +/- 2.6 sigma for the TLD, -2.9% +/- 5.0 sigma for the MOSFET, and +1.3% +/- 1.4 sigma for the treatment planning system. This phantom mouse design is unique, simple, reproducible, and therefore recommended as a standard approach to dosimetry for radiobiological mouse studies by means of any of the detectors used in this study. The authors fully advocate for treatment planning modeling when possible prior to linac-based dose delivery. PMID- 22048494 TI - Validity of thyroid cancer incidence data following the Chernobyl accident. AB - The only clearly demonstrated cancer incidence increase that can be attributed to radiation from the Chernobyl accident is thyroid carcinoma in patients exposed during childhood or adolescence. Significant increases in thyroid disease were observed as soon as 4 y after the accident. The solid/follicular subtype of papillary carcinoma predominated in the early period after the accident. Morphological diagnosis of cancer in such cases, if no infiltrative growth is clearly visible, depends mainly on the nuclear criteria. Outdated equipment and insufficient quality of histological specimens impeded reliable evaluation of the nuclear criteria. Access to foreign professional literature has always been limited in the former Soviet Union. The great number of advanced tumors observed shortly after the accident can be explained by the screening effect (detection of previously neglected cancers) and by the fact that many patients were brought from non-contaminated areas and registered as Chernobyl victims. It is also worth noting that exaggeration of the Chernobyl cancer statistics facilitated the writing of dissertations, financing of research, and assistance from outside the former Soviet Union. "Chernobyl hysteria" impeded nuclear energy production in some countries, thus contributing to higher prices for fossil fuel. The concluding point is that since post-Chernobyl cancers tend on average to be in a later stage of tumor progression, some published data on molecular or immunohistochemical characteristics of Chernobyl-related cancers require reevaluation. PMID- 22048498 TI - Food advertisements: to ban or not to ban? PMID- 22048499 TI - Antenatal screening for Toxoplasma gondii infection at a tertiary care hospital in Riyadh, Saudi Arabia. AB - BACKGROUND AND OBJECTIVES: Congenital toxoplasmosis is associated with significant morbidity and mortality. This study investigates the prevalence of toxoplasmosis among pregnant women. DESIGN AND SETTING: A retrospective study at King Khalid University Hospital, Riyadh from September 2009 to August 2010. PATIENTS AND METHODS: 0 Laboratory data of 2176 pregnant women screened for Toxoplasma gondii in the antenatal care unit were assessed during the study period. The mean (SD) age of the women and the duration of pregnancy were 25 (7.3) years and 18 (7.7) weeks, respectively. Data were extracted for the presence or absence of anti-T gondii immunoglobulin G (IgG) and IgM antibodies. RESULTS: Of 2176 sera tested, 1351 (62%) did not show any evidence of exposure to T gondii. The remaining 825 (38%) samples tested positive for anti-T gondii IgG antibodies, and none was found to have anti-T gondii IgM antibodies in the serum. These data reveal that a significantly high number of women in the antenatal care unit at King Khalid University Hospital in Riyadh had been exposed to T gondii. CONCLUSION: A high prevalence of toxoplasmosis among pregnant women warrants multicenter community-based investigations for assessment of T gondii infection and identification of risk factors for transmission of toxoplasmosis in general, and particularly during pregnancy. PMID- 22048500 TI - Assessment of hepatitis B immunization status after antineoplastic therapy in children with cancer. AB - BACKGROUND AND OBJECTIVES: Hepatitis B is a disease that is preventable with vaccination. Antibody levels after vaccination may be affected by suppression of the immune system due to cancer therapy. Children with cancer have a high risk of hepatitis B virus (HBV) infection. We aimed to assess the pretreatment immunization status against HBV infection and the rate of continuity of immunization after therapy in children with cancer. DESIGN AND SETTING: Retrospective case review of patients treated from 2004 to 2008. PATIENTS AND METHODS: We reviewed the medical records of patients treated in the departments of pediatric hematology and oncology and collected data on immunization history and hepatitis B serology. Anti-HBs antibody titers were compared before and after treatment. RESULTS: This study included 159 (99 males, 60 females) children who had a serologic examination. Antineoplastic therapy had been given for acute leukemia (n=66), non-Hodgkin lymphoma (n=27), Hodgkin lymphoma (n=20), and solid tumors (n=46). Fifty-one patients had not been immunized against HBV prior to the therapy; HBV serology was negative in 49 of these patients and HBsAg was positive in 2 patients. Anti-HBs antibody positivity was present in 99 of 108 patients with an immunization history, whereas no vaccination response was present in 9 patients. The titer of anti-HBs antibody was decreased below the protection level in 33 (33%) patients with positive anti-HBs antibody, whereas the protection level was found to be maintained in 66 (67%) patients. The most significant decrease (63.6%) was observed in leukemia patients. Posttreatment HBsAg and HBV DNA positivity was detected in two of the patients with negative pretreatment serology, whereas no HBV infection developed in the group with positive anti-HBs antibody. CONCLUSIONS: This study demonstrated the importance of routine childhood vaccination in reducing the risk of HBV infection in patients with cancer. PMID- 22048501 TI - Success rate and neonatal morbidities associated with early extubation in extremely low birth weight infants. AB - BACKGROUND AND OBJECTIVES: Mechanical ventilation improves survival of preterm infants with respiratory failure. The aim of this study was to determine the success rate and short-term neonatal morbidities of early extubation in extremely low birth weight (ELBW) infants in a tertiary care neonatal intensive care unit (NICU). DESIGN AND SETTING: Retrospective cohort study of ELBW infants admitted to a tertiary. neonatal intensive care referral unit from January 1 st to December 31 st , 2005. PATIENTS AND METHODS: The primary outcome was the success rate of early extubation in ELBW infants who were intubated at delivery, extubated in the first 48 hours of life, and did not require reintubation within 72 hours following extubation. RESULTS: Thirty of the 95 eligible infants were extubated early; of these 30 infants, 24 (80%) had a successful extubation. Infants extubated early had a higher mean birth weight (855 vs 745 g; P<.0001) and gestational age (27.3 vs 25.6 weeks; P<.0001). ELBW infants who were extubated early had lower rates of death (relative risk [RR], 0.05; 95% CI, (0.0, 0.79); P=.003), intraventricular hemorrhage (IVH) (RR, 0.23; 95% CI, 0.08, 0.70; P=.008), and patent ductus arteriosus (PDA) (RR, 0.76; 95% CI, 0.60, 0.98; P=.03) compared with those who remained ventilated beyond the first 48 hours of life. CONCLUSION: The rate of successful early extubation in our unit exceeded the sole previously reported rate. Successful early extubation was associated with lower rates of death, IVH, and PDA in ELBW infants. PMID- 22048502 TI - Short-term outcome of very low-birth-weight infants in a tertiary care hospital in Saudi Arabia. AB - BACKGROUND AND OBJECTIVE: Published data on short-term outcomes of very low birth weight infants from Saudi Arabia are limited. In the present study, our objective was to describe and analyze the outcomes of very low birth weight infants admitted to our neonatal intensive care unit and to compare the results with data published by the National Institute of Child Health and Development. DESIGN AND SETTING: This study was a retrospective analysis of prospectively collected data from a single tertiary care center over a three years period. PATIENTS AND METHODS: Biodemographic data and data regarding multiple outcome measures were analyzed for infants with birth weight of 1500 g or less. Data were obtained from our neonatal intensive care unit database. RESULTS: Our results included a total of 186 infants with birth weights of 1500 g or less. Of these infants, 154 (82.8%) survived to discharge. Seventy-six (40.9%) were male, and mean (SD) gestational age (GA) was 29 (2.9) weeks with a range of 21 weeks, 6 days to 36 weeks, 2 days. Mean (SD) birth weight was 1062 (302) g with a range of 420 to 1495 g. Fifty-seven (30.6%) infants were characterized as small for gestational age. Antenatal steroids were given to 74.2% of mothers. Eighty-five percent of infants were born by cesarean section. The rate of bronchopulmonary dysplasia was 17.7%, patent ductus arteriosus 31.2%, intraventricular hemorrhage 12.9%, periventricular leukomalacia 3.8%, necrotizing enterocolitis 7.5%, retinopathy of prematurity 28.3%, and late-onset sepsis was 21.9%. CONCLUSION: In this population of very low birth weight infants, survival rates and complications of prematurity were comparable to international data. PMID- 22048503 TI - beta2-adrenergic receptor gene polymorphisms in normal and asthmatic individuals in the Eastern Province of Saudi Arabia. AB - BACKGROUND AND OBJECTIVES: Several polymorphisms of the beta2-adrenergic receptor (beta2-AR) gene have been identified, including the amino acid substitution from arginine (Arg) to glycine (Gly) at codon 16 and from glutamine (Gln) to glutamic acid (Glu) at codon 27. These substitutions affect receptor function and show significantly more agonist-promoted receptor down-regulation than cells expressing the Arg 16/Gln 27 variants. Although the ethnic dependency of this polymorphism has been described in other populations, no studies investigating its relationship to asthma have been conducted in the Saudi population . Therefore, our main objective was to determine the prevalence of these two mutations among patients with asthma in the Eastern Province and in matched healthy controls. DESIGN AND SETTING: A case-control study conducted at a university hospital among Saudi patients. PATIENTS AND METHODS: Blood samples were collected from 73 asthmatic patients and from 85 controls, and the beta2-AR gene polymorphisms at codon 16 and codon 27 were assessed by restriction fragment length polymorphism. RESULTS: Although a significant difference was observed in genotype frequencies at codon 16 (Arg/Gly) between the asthmatic and normal control subjects (P<.05), no statistically significant difference was observed in allele frequencies between the two groups. In addition, no statistically significant differences were observed in genotype and allele frequencies at codon 27 (Gln/Glu) between the normal (control) and asthmatic groups (beta2=0.75, P>.68). Using the THESIAS statistical program, no significant association of any haplotype with asthma was found. CONCLUSIONS: Our findings indicate a poor association of individual single-nucleotide polymorphisms with asthma. However, further study is required to ascertain the interactions of different haplotypes and the response of patients with different haplotypes to various treatments. PMID- 22048504 TI - Home caregivers' satisfaction with the services provided by Riyadh Military Hospital's home support program. AB - BACKGROUND AND OBJECTIVES: The satisfaction of the family is essential to the success of home care support services. This study aimed to assess home caregivers' satisfaction with support services and to identify potential factors affecting their satisfaction. DESIGN AND SETTINGS: The study was conducted in the Family and Community Medicine Department at Riyadh Military Hospital using cross sectional design over a period of six months. PATIENTS AND METHODS: Two hundred forty participants were recruited by systematic random sampling from the division registry. Data were collected through telephone calls using a designed structured interview form. All research ethics principles were followed. RESULTS: The response rate was 76.25%. Most caregivers were patients' sons or daughters. The duration of patients' disabling illnesses varied from less than 1 year to up to 40 years. The majority of caregivers agreed that a home care services team provided the proper healthcare-related support to the patients and improved caregivers' self-confidence in caring for their patients. Overall, on a scale of 100%, the median level of satisfaction was 90%, and 73.2% of caregivers had a satisfaction score of 75% or higher. Increased age, female gender, and more frequent home visits were positive independent factors associated with caregivers' satisfaction scores. CONCLUSION: Although most caregivers are satisfied with the services provided by a home care support program, there are still areas of deficiency, particularly in physiotherapy, vocational therapy, and social services. The implications are that caregivers need to be educated and trained in caring for their patients and need to gain self-confidence in their skills. The program's administration should improve physiotherapy, vocational therapy, social services, and procedures for hospital referral. PMID- 22048505 TI - The effect of uterine blood supply cutoff during myomectomy. AB - BACKGROUND AND OBJECTIVE: Myomectomy is considered a highly morbid procedure due to the risk of high intraoperative blood loss. Meticulous surgical techniques can reduce operative morbidity. Our aim was to evaluate and compare the intraoperative blood loss between two surgical techniques: 1) the uterine vascular cutoff technique and 2) the classical technique. DESIGN AND SETTING: Retrospective chart review conducted between 1 July 2008 until 30 June 2010 in a tertiary care referral center to compare surgical outcomes of two groups. PATIENTS AND METHODS: The sample included 136 patients: 30 patients had their surgeries performed with the uterine vascular cutoff technique, and the remainder (106 patients) had myomectomies performed with the classical technique. The uterine vascular cutoff technique was performed by the same surgeon for all 30 patients, whereas myomectomy with the classical technique was performed by several gynecologists. RESULTS: There was no significant difference between the two groups in parity and operation time; however, patients in the first group had a statistically significant higher mean age (39.1 [7.6] vs 35.8 [6.9] years; P=.025) and, on average, bigger fibroid size by gestational week (20.1 [7.3] vs 17 [5.2] weeks; P=.0094), with standard deviation shown in parentheses. There was a statistically significant lesser drop in hemoglobin concentration among patients in the first group (1.23 [1.2] vs 2.25 [1.4] g/dL; P=.0003), and the postoperative hemoglobin was significantly higher in the first group (10.5 [1.6] vs 9.7 [1.7] g/dL; P=.036). The hospital stay was shorter for patients in the first group (5.8 [1.7] vs 7.1 [2.9] days; P=.031). CONCLUSION: The vascular cutoff technique leads to less intraoperative blood loss without increasing the operative time, patients tolerate this technique very well, and the technique is associated with shorter hospital stay, all of which could contribute to less postoperative morbidity. PMID- 22048506 TI - Influence of vitamin D levels on bone mineral density and osteoporosis. AB - BACKGROUND AND OBJECTIVES: The effects of vitamin D on bone mass remain to be understood. This study was conducted with the objective of evaluating the influence of 25-hydroxyvitamin D (25OHD) levels on bone mineral density (BMD) among Saudi nationals. DESIGN AND SETTING: Cross-sectional study carried out at university hospital from 1 February 2008 to 31 May 2008. SUBJECTS AND METHODS: Healthy Saudi men and women in the peak bone mass (PBM) age group and those aged >= 50 years were recruited from the outpatient department of King Fahd University Hospital, Al Khobar, Saudi Arabia, between February 1, 2008, and May 31, 2008. Patient age and sex were documented, and body mass index was calculated. Hematological, biochemical, and serum 25OHD tests were performed. BMD was determined by dual-energy x-ray absorptiometry of the upper femur and lumbar spine. Patients were divided into three groups, based on their 25OHD level. RESULTS: Data from 400 patients were analyzed. Among individuals with a normal 25OHD level, 50% of women and 7% of men in the PBM age group and 26.4% of women and 49.2% of men aged >= 50 years had low bone mass. In patients with 25OHD insufficiency, 84.2% of women and 88.9% of men in the PBM age group and 83.3% of women and 80% of men aged >= 50 years had low bone mass. Results for patients with 25OHD deficiency revealed that none of the men and women in the PBM age group or >= 50 years old had normal BMD. Significant positive correlations between 25OHD level and BMD and significant negative correlations with parathyroid hormone were shown in most of the groups. CONCLUSIONS: This study showed that the vitamin D level significantly influences BMD reading among Saudi individuals. Evaluation and treatment of hypovitaminosis D should be considered during management of low bone mass. PMID- 22048507 TI - Can the duration of vomiting predict postoperative outcomes in hypertrophic pyloric stenosis? AB - BACKGROUND AND OBJECTIVES: Hypertrophic pyloric stenosis (HPS) is a common cause of gastric outlet obstruction (GOO) in infants. Prolonged GOO is believed to result in acid and electrolyte disturbances, gastric atony, and delayed postoperative recovery. We studied the impact of prolonged vomiting as an indicator of GOO symptoms on the post-operative outcomes in HPS. DESIGN AND SETTING: A retrospective chart review of all patients who underwent pyloromyotomy at a tertiary care center between February 1997 and February 2009. PATIENTS AND METHODS: The duration of pre-operative vomiting was correlated with presenting electrolytes and acid-base balances, postoperative time to full feed, postoperative morbidity and duration of hospitalization. RESULTS: Forty-seven patients were identified. At presentation, the median (range) for duration of symptoms was 14 (3-60) days, and surgeries were performed at 2 (0-6) days after admission. Apart from one case of postoperative wound infection, all patients had an unremarkable recovery. The unusually prolonged duration of vomiting in our cohort did not correlate with the mean (SD) preoperative chloride level of 93.9 (8.8) mEq/L, mean (SD) pH level of 7.5 (0.9), mean postoperative time to full feeding of 31 (15.1) hours, or mean duration of hospitalization of 5.1 (2.2) days. CONCLUSION: Duration of vomiting in HPS at presentation does not seem to have a significant impact on the postoperative outcomes. PMID- 22048509 TI - Prevalence of depressive disorders in the elderly. AB - Community-based mental health studies have revealed that the point prevalence of depressive disorders in the elderly population of the world varies between 10% and 20%, depending on cultural situations. A retrospective study based on analysis of various study reports was conducted, to determine the median prevalence rates of depressive disorders in the elderly population of India and various other countries in the world. All the studies that constituted the sample were conducted between 1955 and 2005. Included are only community-based, cross sectional surveys and some prospective studies that had not excluded depression at baseline. These studies were conducted on a homogenous community of the elderly population in the world, who were selected by a simple random sampling technique. After applying the inclusion and exclusion criteria on published and indexed articles, 74 original research studies that surveyed a total of 487,275 elderly individuals, in the age group of 60 years and above, residing in various parts of the world, were included for the final analysis. The median prevalence rate and its corresponding interquartile range were calculated. The chi-square test and chi-square for linear trend were applied. A P value of <.05 was considered as statistically significant. The median prevalence rate of depressive disorders in the world for the elderly population was determined to be 10.3% (interquartile range [IQR], 4.7%-16.0%). The median prevalence rate of depression among the elderly Indian population was determined to be 21.9% (IQR, 11.6% 31.1%). Although there was a significant decrease in the trend of world prevalence of geriatric depression, it was significantly higher among Indians, in recent years, than the rest of the world. PMID- 22048508 TI - Knowledge and practices of, and attitudes towards, the use of hair dyes among females visiting a teaching hospital in Riyadh, Saudi Arabia. AB - BACKGROUND AND OBJECTIVES: Use of hair dye is extremely common worldwide. However, our literature search failed to find studies concerning the knowledge and attitudes of the public with regard to hair dyes. We sought to explore the knowledge and practices of, and attitudes towards, the use of hair dye among females. DESIGN AND SETTING: A cross-sectional survey conducted on females who attended various outpatient clinics at King Khalid University Hospital in Riyadh, Saudi Arabia, a tertiary referral hospital open to the general public. PATIENTS AND METHODS: A self-administered questionnaire about the use of hair dyes was distributed randomly among females attending the outpatient clinics at a university hospital in 2008. RESULTS: The response rate was 87.2%, with completion of 567 of the 650 distributed questionnaires. The mean (SD) age of respondents was 32.0 (10.2) years. Among respondents, 82.6% (464/562) had at some point dyed their hair. Furthermore, 69.3% (334/482) had dyed their hair in the past 12 months. The mean (SD) age of the participants when they first dyed their hair was 22.2 (7.1) years (range, 7-50). Of the participants, 76.8% (354/461) used permanent dyes, and about the same percentage of participants believed such dyes were the safest hair dye type. However, 52.4% (278/531) of the participants believed that hair dyes are harmful, and 36% (191/531) believed that hair dyes could cause cancer. Younger females tend to dye their hair less frequently (P<.001), whereas those with less education tend to dye their hair more frequently (P=.013). CONCLUSION: Use of hair dye is very common among females. Because the practice starts at a very young age, we conclude that hair dyes are overused and misused. The public should be informed about the risks associated with excessive hair dye use. PMID- 22048510 TI - Myocardial perfusion scintigraphy: techniques, interpretation, indications and reporting. AB - Myocardial perfusion single photon emission-computed tomography (MPS) has been one of the most important and common non-invasive diagnostic cardiac test. Gated MPS provides simultaneous assessment of myocardial perfusion and function with only one study. With appropriate attention to the MPS techniques, appropriate clinical utilization and effective reporting, gated MPS will remain a useful diagnostic test for many years to come. The aim of this article is to review the basic techniques of MPS, a simplified systematic approach for study interpretation, current clinical indications and reporting. After reading this article the reader should develop an understanding of the techniques, interpretation, current clinical indications and reporting of MPS studies. PMID- 22048511 TI - Preventing child abuse and neglect in Saudi Arabia: are we ready? AB - Although child abuse and neglect (CAN) have been recognized by medical professionals for the last 20 years, child protection services and child maltreatment prevention programs are still emerging in Saudi Arabia. This paper will review the progress made in the country in terms of recognition and implementation of child protection services. Furthermore, it will draw attention to the essential steps required to start child maltreatment prevention programs, as CAN prevention is currently viewed as a global healthcare priority with an emphasis on evidence-based interventions. In addition, this paper will assess Saudi Arabia's readiness to prevent CAN and the challenges that will be faced by the professionals in implementing evidence-based CAN prevention programs. PMID- 22048512 TI - Right hepatic arterial pseudoaneurysm with hemobilia following minilaparotomy cholecystectomy: a rare complication. AB - Hepatic arterial pseudoaneurysm with hemobilia occurs less frequently as a complication of minilaparotomy cholecystectomy than laparoscopic cholecystectomy; however, given its severe nature, it needs to be managed promptly. This report presents a case of right hepatic artery pseudoaneurysm with hemobilia in a 36 year-old woman who underwent minilaparotomy cholecystectomy 5 weeks earlier. Angiography with embolization was carried out as definitive treatment. PMID- 22048513 TI - Three cases of macrofollicular variant of papillary thyroid carcinoma. AB - The macrofollicular variant of papillary thyroid carcinoma (MFPTC) is a well established entity with characteristic large follicles containing pale colloid and lined by cells with nuclear features of papillary thyroid carcinoma (PTC). In this study, we present three cases of MFPTC, along with a brief review of the literature. For all three of our cases, the histology of the resected specimen showed predominantly macrofollicular structures lined by cells with nuclear characteristics of PTC. Immunohistochemically, the three cases show positivity for galactin-3, cytokeratin-19, and HBME-1. These cases will help us in understanding the distinction from other benign and malignant follicular lesions of the thyroid, which is of utmost importance. The key to diagnosis is a high power examination of any macrofollicular lesion of the thyroid. PMID- 22048514 TI - Percutaneous coronary intervention in two patients with a solitary coronary artery from the right coronary sinus of Valsalva. AB - Two patients with a common coronary artery arising from the right sinus of Valsalva, who underwent coronary angiography and percutaneous coronary intervention following an acute coronary syndrome, are presented. The anatomic description based on previously published classification schemes is described. The clinical implications of this rare coronary anomaly and interventional considerations are addressed. PMID- 22048515 TI - Cerebral venous thrombosis associated with homozygous factor V Leiden mutation in a 15-year-old girl of Tunisian origin. AB - Cerebral venous thrombosis (CVT) is a rare disease. It has numerous and complex etiologies. Inherited or acquired prothrombotic states play a key role in the development of this disease, such as factor V G1691A mutation (FV Leiden). A 15 year-old girl presented to the Department of Neurology with a complaint of severe headache with visual blurring. The diagnosis of CVT was not initially suspected because of the patient's condition on presentation. An MRI showed thrombosis in the superior sagittal sinus, confirming venous stroke. Anticardiolipin and antiphospholipid antibodies were assessed. In addition, inherited prothrombotic defects, such as protein C, protein S, and antithrombin deficiencies, and genetic mutations for FV Leiden, prothrombin gene G20210A (FII G20210A), and methyltetrahydrofolate reductase C677T (MTHFR C677T) were studied. All results were unremarkable except for the unique homozygous FV Leiden mutation, which likely contributed to this prothrombotic situation. This study highlights the fact that FV Leiden may play a significant role in the onset of CVT in young patients. PMID- 22048516 TI - Single-port laparoscopic splenectomy for idiopathic thrombocytopenic purpura. AB - Laparoscopic splenectomy has been performed with an average of 4 trocars since the early 1990s, and it has become the gold standard for elective splenectomy. Recently, single-port laparoscopic (SPL) surgery has emerged as an alternative to multiport laparoscopy, but SPL splenectomy in a patient with idiopathic thrombocytopenic purpura (ITP) has not been reported to date in Saudi Arabia or the region. A case report of SPL splenectomy in a patient with ITP is briefly described along with the surgical technique needed for such a procedure. The patient was an otherwise healthy 24-year-old female woman with medically refractory ITP and a platelet count of 2200. A standard splenectomy was performed using a SPL technique. The patient did well intraoperatively and postoperatively, was happy with her incision, and was discharged home with no complications 3 days after the procedure. In conclusion, SPL splenectomy is feasible in select patients and may provide a less painful, cosmetically better alternative. PMID- 22048517 TI - Reply to comment on Ahmad et al. Ann Saudi Med 2011;31:24-8. PMID- 22048518 TI - Recurrent abdominal pain and bloody ascites. PMID- 22048519 TI - RE: Six-year outcome of the national premarital screening and genetic counseling program for sickle cell disease and beta-thalassemia in Saudi Arabia. PMID- 22048520 TI - Comment on "Predictive value of the cow's milk skin prick test in infantile colic". PMID- 22048521 TI - A 52-year-old man with no known history of hand trauma presenting to the clinic with a pulsatile mass in his right palm. PMID- 22048522 TI - Prediction of in vivo hepatic clearance and half-life of drug candidates in human using chimeric mice with humanized liver. AB - Accurate prediction of pharmacokinetics (PK) parameters in humans from animal data is difficult for various reasons, including species differences. However, chimeric mice with humanized liver (PXB mice; urokinase-type plasminogen activator/severe combined immunodeficiency mice repopulated with approximately 80% human hepatocytes) have been developed. The expression levels and metabolic activities of cytochrome P450 (P450) and non-P450 enzymes in the livers of PXB mice are similar to those in humans. In this study, we examined the predictability for human PK parameters from data obtained in PXB mice. Elimination of selected drugs involves multiple metabolic pathways mediated not only by P450 but also by non-P450 enzymes, such as UDP-glucuronosyltransferase, sulfotransferase, and aldehyde oxidase in liver. Direct comparison between in vitro intrinsic clearance (CL(int,in vitro)) in PXB mice hepatocytes and in vivo intrinsic clearance (CL(int,in vivo)) in humans, calculated based on a well stirred model, showed a moderate correlation (r2 = 0.475, p = 0.009). However, when CL(int,in vivo) values in humans and PXB mice were compared similarly, there was a good correlation (r2 = 0.754, p = 1.174 * 10-4). Elimination half-life (t(1/2)) after intravenous administration also showed a good correlation (r2 = 0.886, p = 1.506 * 10-4) between humans and PXB mice. The rank order of CL and t(1/2) in human could be predicted at least, although it may not be possible to predict absolute values due to rather large prediction errors. Our results indicate that in vitro and in vivo experiments with PXB mice should be useful at least for semiquantitative prediction of the PK characteristics of candidate drugs in humans. PMID- 22048523 TI - Simultaneous structural variation discovery among multiple paired-end sequenced genomes. AB - With the increasing popularity of whole-genome shotgun sequencing (WGSS) via high throughput sequencing technologies, it is becoming highly desirable to perform comparative studies involving multiple individuals (from a specific population, race, or a group sharing a particular phenotype). The conventional approach for a comparative genome variation study involves two key steps: (1) each paired-end high-throughput sequenced genome is compared with a reference genome and its (structural) differences are identified; (2) the lists of structural variants in each genome are compared against each other. In this study we propose to move away from this two-step approach to a novel one in which all genomes are compared with the reference genome simultaneously for obtaining much higher accuracy in structural variation detection. For this purpose, we introduce the maximum parsimony-based simultaneous structural variation discovery problem for a set of high-throughput sequenced genomes and provide efficient algorithms to solve it. We compare the proposed framework with the conventional framework, on the genomes of the Yoruban mother-father-child trio, as well as the CEU trio of European ancestry (both sequenced by Illumina platforms). We observed that the conventional framework predicts an unexpectedly high number of de novo variations in the child in comparison to the parents and misses some of the known variations. Our proposed framework, on the other hand, not only significantly reduces the number of incorrectly predicted de novo variations but also predicts more of the known (true) variations. PMID- 22048524 TI - Early life-stage toxicity of eight pharmaceuticals to the fathead minnow, Pimephales promelas. AB - Human pharmaceuticals are routinely being detected in the environment, and there is growing concern about whether these drugs could elicit effects on aquatic organisms. Regulatory paradigms have shifted accordingly, with a greater emphasis on chronic toxicity data compared with acute data. The Organisation for Economic Co-operation and Development 210 Early Life Stage Test has been proposed as a good measure of the potential for pharmaceuticals to elicit chronic toxicity. To begin building a data set regarding the early life-stage toxicity of pharmaceuticals to fish, fathead minnows (FHM) were exposed to amiodarone, carbamazepine, clozapine, dexamethasone, fenofibrate, ibuprofen, norethindrone, or verapamil. Survival and growth were used to assess chronic toxicity in FHM at 28 days posthatch. Exposure of FHM to carbamazepine, fenofibrate, and ibuprofen resulted in no significant adverse effects at the concentrations tested. FHM survival was not impacted by verapamil exposure; however, growth was significantly decreased at 600 MUg/L. Dexamethasone-exposed FHM showed a significant decrease in survival at a concentration of 577 MUg/L; however, growth was not impacted at the concentration tested. Norethindrone exposure resulted in a significant decrease in survival and dry weight at 14.8 and 0.74 MUg/L, respectively. Exposure to amiodarone and clozapine resulted in a significant decrease in survival and a significant increase in growth at concentrations of 1020 and 30.8 MUg/L, respectively. Although the effect levels derived in this study are greater then concentrations observed in the environment, these data suggest that synthetic progestins may require additional research. PMID- 22048525 TI - Epidermolysis bullosa in a newborn. PMID- 22048526 TI - Calculation and experimental verification of the RBE-weighted dose for scanned ion beams in the presence of target motion. AB - We present an algorithm suitable for the calculation of the RBE-weighted dose for moving targets with a scanned particle beam. For verification of the algorithm, we conducted a series of cell survival measurements that were compared to the calculations. Calculation of the relative biological effectiveness (RBE) with respect to tumor motion was included in the treatment planning procedure, in order to fully assess its impact on treatment delivery with a scanned ion beam. We implemented an algorithm into our treatment planning software TRiP4D which allows determination of the RBE including its dependence on target tissue, absorbed dose, energy and particle spectra in the presence of organ motion. The calculations are based on time resolved computed tomography (4D-CT) and the corresponding deformation maps. The principal of the algorithm is illustrated in in silico simulations that provide a detailed view of the different compositions of the energy and particle spectra at different target positions and their consequence on the resulting RBE. The calculations were experimentally verified with several cell survival measurements using a dynamic phantom and a scanned carbon ion beam. The basic functionality of the new dose calculation algorithm has been successfully tested in in silico simulations. The algorithm has been verified by comparing its predictions to cell survival measurements. Four experiments showed in total a mean difference (standard deviation) of -1.7% (6.3%) relative to the target dose of 9 Gy (RBE). The treatment planning software TRiP is now capable to calculate the patient relevant RBE-weighted dose in the presence of target motion and was verified against cell survival measurements. PMID- 22048528 TI - Globalization of Ayurveda: New horizons! PMID- 22048527 TI - High manoeuvring costs force narrow-winged molossid bats to forage in open space. AB - Molossid bats are specialised aerial-hawkers that, like their diurnal ecological counterparts, swallows and swifts, hunt for insects in open spaces. The long and narrow wings of molossids are considered energetically adapted to fast flight between resource patches, but less suited for manoeuvring in more confined spaces, such as between tree-tops or in forest gaps. To understand whether a potential increase in metabolic costs of manoeuvring excludes molossids from foraging in more confined spaces, we measured energy costs and speed of manoeuvring flight in two tropical molossids, 18 g Molossus currentium and 23 g Molossus sinaloae, when flying in a ~500 m(3) hexagonal enclosure (~120 m(2) area), which is of similar dimensions as typical forest gaps. Flight metabolism averaged 10.21 +/- 3.00 and 11.32 +/- 3.54 ml CO(2) min(-1), and flight speeds 5.65 +/- 0.47 and 6.27 +/- 0.68 m s(-1) for M. currentium and M. sinaloae respectively. Metabolic rate during flight was higher for the M. currentium than for the similar-sized, but broader-winged frugivore Carollia sowelli, corroborating that broad-winged bats are better adapted to flying in confined spaces. These higher metabolic costs of manoeuvring flight may be caused by having to fly slower than the optimal foraging speed, and by the additional metabolic costs for centripetal acceleration in curves. This may preclude molossids from foraging efficiently between canopy trees or in forest gaps. The surprisingly brief burst of foraging activity at dusk of many molossids might be related to the cooling of the air column after sunset, which drives airborne insects to lower strata. Accordingly, foraging activity of molossids may quickly turn unprofitable when the abundance of insects decreases above the canopy. PMID- 22048529 TI - Historical development of basic concepts of Ayurveda from Veda up to Samhita. PMID- 22048530 TI - Effect of Triphaladi Avaleha as an adjuvant therapy in the management of Thalassemia. AB - Thalassemia is the most common inherited single-gene (autosomal recessive) disorder in the world. Scientists worldwide predict that thalassemia will become a considerable health issue in the next century. It is a new disease entity for Ayurvedic medicine, and hence, it is called Anukta Vyadhi in Ayurveda; but we can understand it by careful scrutiny of the clinical presentation and the investigation results described in the available literature. Modern medical management is aimed at maintaining the hemoglobin level at 10 - 12 g/dl. A post transfusion hemoglobin level of 9.5 g/dl is said to be sufficient to maintain active life. Thus, blood transfusion therapy is the only treatment, but it can result in hemosiderosis (iron overload), a complication with a fatal outcome. The transfusional iron overload is compounded by increased intestinal absorption of iron. The most important factors associated with survival, and also those deciding the outcome of bone marrow transplant (the only curative therapy) are, age at which chelation therapy is introduced and the success with which serum ferritin is maintained below 2500 ng/ml. Iron chelators used in modern medicine to achieve this goal are expensive and associated with side effects, and hence, associated with poor adherence to the treatment. The present study is an endeavor to explore the efficacy of Triphaladi Avaleha as an iron chelator in the management of thalassemia, in comparison to a control group managed by routine modern therapy. PMID- 22048531 TI - A comparative study of Kaishora Guggulu and Amrita Guggulu in the management of Utthana Vatarakta. AB - Vatarakta is the major example of Vata vyadhi, caused due to avarana pathology. The scenario of Utthana Vatarakta occurred owing to the margavarana pathology, which can very well be correlated with atherosclerotic peripheral arterial disease. The literature enlists a number of Guggulu prayogas in the management of Vatarakta. An additional cavernous revise was indispensable to bring out the precise outcome of these products. Keeping these visions in mind, the particular comparative study was performed with Kaishora guggulu and Amrita guggulu, which are explained in the same context. This is a single-blind comparative clinical study with a pre-test and post-test design, wherein a minimum of 30 patients of either sex, suffering from Utthana Vatarakta, in an age limit of 16 to 70 years, were selected and randomly categorized into two groups. The 15 patients of group A were treated with oral administration of Tab Kaishora guggulu 1 g thrice a day and the group B patients with Tab Amrita guggulu of the same dose pattern with anupana of lukewarm water. The therapeutic effect of the treatment was assessed in both the groups based on specific subjective and objective parameters. The results obtained were analyzed statistically in both the groups and the comparative effect was assessed using the unpaired "t" -test. In the present study, 80% of the patients from both the groups had madhumeha (Diabetes mellitus), shonita mada (Hypertension) or both. Fifty percent of the patients in group A and nearly 60% of the patients in group B, suffering from Utthana Vatarakta, had the habit of smoking.In both the groups, a statistically significant improvement was observed in all the criteria of assessment. The outcome of the study revealed an identical therapeutic efficacy of Kaishora guggulu and Amrita guggulu in Utthana Vatarakta. The use of Kaishora guggulu or Amrita guggulu as shamana Aushadhas was a perfect selection in the management of rakta margavaranajanya Utthana Vatarakta. PMID- 22048533 TI - Effect of Kumari Taila Uttar Basti on fallopian tube blockage. AB - The present study was carried out to evaluate the role of Uttar Basti in tubal blockage, in order to establish it as a safer and cost-effective Ayurvedic treatment modality. The criteria for selection of patients and assessment of results were unilateral or bilateral tubal blockage diagnosed in hysterosalpingography (HSG). A total of 16 patients in the reproductive age group were registered for the study, with 62.50% unilateral and 37.50% bilateral tubal blockage. Fifteen patients completed the course of treatment. The patients with an evidence of active infection or chronic diseases were excluded. Kumari Taila was selected for its Vata Kapha Shamaka and Lekhana properties. The dose of Uttar Basti was 5 ml with duration of two consecutive cycles (six days of Uttar Basti in each cycle with an interval of three days in between). Uttar Basti was administered, after cessation of menstruation, to the screened patients, through hematological, urinary, and serological (HIV, VDRL, HBsAg) investigations. The tubal blockage was removed in 80% of the patients, and 40% of the patients had conceived within the follow-up period of two months. The results suggest that Uttar Basti is a highly significant treatment modality for tubal blockage, with no apparent complications. PMID- 22048532 TI - Efficacy of Rasayana Avaleha as adjuvant to radiotherapy and chemotherapy in reducing adverse effects. AB - Cancer is the most dreadful disease affecting mankind. The available treatments such as chemotherapy and radiotherapy have cytotoxic effects, which are hazardous to the normal cells of the patient, causing many unnecessary effects. This further leads to complications of the therapy, impaired health, and deterioration of quality of life, resulting in mandatory stoppage of the treatment. In the present study, the efficacy of an Ayurvedic formulation, Rasayana Avaleha, has been evaluated as an adjuvant medication to modern radiotherapy and chemotherapy. A total of 36 cancer patients were registered in this trial and were divided into two groups, group A and group B. In group A, the patients were treated with radiotherapy and chemotherapy along with adjuvant Rasayana Avaleha (RT + CT + RA), while in group B only radiotherapy and chemotherapy (RT + CT) were given, as the control group. After assessing the results, it was observed that Rasayana Avaleha gave better results in controlling the adverse effect of chemotherapy and radiotherapy in comparison with the control group. Therefore, Rasayana Avaleha has proved to be an effective adjuvant therapy in protecting patients from the adverse effects of chemotherapy and radiotherapy. PMID- 22048534 TI - Management of Amavata with 'Amrita Ghrita': A clinical study. AB - Amavata is a disease caused due to the vitiation or aggravation of Vayu associated with Ama. Vitiated Vayu circulates the Ama all over the body through Dhamanies, takes shelter in the Shleshma Sthana (Amashaya, Sandhi, etc.), producing symptoms such as stiffness, swelling, and tenderness in small and big joints, making a person lame. The symptoms of Amavata are identical to rheumatism, which include rheumatoid arthritis and rheumatic fever. It is observed that rheumatism is an autoimmune disorder, which is among the collagen disorders having strong and significant parlance with Amavata. Various drug trials were already carried out on Amavata, yet there is a lacuna in the management of Amavata. Hence, in the present clinical study, 28 patients were selected and kept on 'Amrita Ghrita'. All the patients were investigated for complete blood count (CBC), rheumatoid arthritis (RA) titer, Antistreptolysin O (ASO) titer, C-reactive protein (CRP) titer, platelet count, urine routine, and microscopic, before and after treatment. The collected data was distributed according to age, sex, and prakruti, and a t-test was applied for the clinical assessment of the subjective and objective parameters of 'Amrita Ghrita,' and it has shown significant reduction in the positivity of the RA titer (t > 5.09, at the 0.001% level), ASO titer (t > 4.08, at the 0.001% level), and CRP titer (t > 4.82, at the 0.001% level), and weight gain (t > 5.12, at the 0.001% level), as also an increase in Hb% (t >9.22, at the 0.001% level), and platelet count (t> 5.90, at the 0.001% level), and decrease in ESR (t > 9.70, at the 0.001% level). PMID- 22048535 TI - The role of psychic factors in pathogenesis of essential hypertension and its management by Shirodhara and Sarpagandha Vati. AB - This clinical trial was conducted to evaluate the efficacy of Shirodhara and that of Sarpagandha Vati in essential hypertension. A total 47 patients were selected for study, out of which 40 patients (20 in each group) completed the course of treatment. Study subjects were randomly allotted into two groups, with one group being treated with Shirodhara and the other with Sarpagandha Vati. Specialized Ayurvedic rating scales like Manasa Pariksha Bhava as well as the Hamilton Anxiety Rating Scale were adopted to assess the effect of therapy. The effects of treatment on the chief complaints and the associated complaints were also evaluated. The results in the Shirodhara group were better than that in the Sarpagandha group. Although both Sarpagandha Vati and Shirodhara helped in reducing systolic and diastolic pressures, the effect of Shirodhara was more marked. PMID- 22048536 TI - A clinical trial of Pippali (Piper longum Linn.) with special reference to Abheshaja. AB - The classification of Dravya has been undertaken in many ways, but according to the medicinal value, they are mainly divided into two - Bheshaja and Abheshaja. No study has been documented on Abheshaja to date as per the scholar's knowledge. Therefore, the present study was carried out to understand the concept of Abheshaja by a practical study. The drug Pippali (Piper Longum Linn.) has been contraindicated to be used for a longer duration. A clinical study was carried out on patients with Kaphaja Kasa, to evolve and assess if the drug acts as Abheshaja or not, and if yes, then under what circumstances. The patients of Kaphaja Kasa had been selected by the random sampling method. They were randomly divided into two groups - Group A and Group B. In Group A, test drug Pippali Churna was administered. Group B was a standard control group and Vasa Churna was given to this group. The dose of both the drugs was 4 g B.I.D. The result was assessed after three weeks of drug administration with the help of a specially prepared proforma. All the important hematological, biochemical, urine, and stool investigations were carried out. There was no adverse drug reaction (ADR) observed after the administration of Pippali in this particular study. PMID- 22048537 TI - Clinical efficacy of Shatapushpa (Anethum sowa Kurz.) powder in the management of Artava kshaya (oligomenorrhoea). AB - A clinical trial was carried out on 30 oligomenorrhoea [Artava Kshaya] patients aged between 15 and 35 years having complaints of irregular, scanty and painful menstruations. The patients were registered from OPD and IPD of Gopabandhu Ayurveda Mahavidyalaya Puri. They were administrated Satapuspa churna for three months in a dose of 5 g twice daily with cow grita. The specific investigations were done in order to exclude TB endometritis, endocrine disorders, diabetes and heart disease. The clinical assessment was carried out in thirty days intervals. It is inferred that the study discloses the effect of satapuspa churna on irregularity of interval of menstruation [90.47%], duration of menstruation [79.37%], amount of blood flow [90.00%] and pain during menstruation [100.00%] which were highly significant in clinical study. No untoward side effect was noticed during clinical trial. PMID- 22048538 TI - A clinical study on the role of ama in relation to Grahani Roga and its management by Kalingadi Ghanavati and Tryushnadi Ghrita. AB - Grahani and Agni are having Adhara-Adheya-Sambandha. Grahani is described as an Agni Adhishthana by most of the acharyas. Mandagni is a root cause of Ama Dosha and it is the crucial factor for manifestation of most of the diseases. Among them, Grahani is the prime disease of gastro-intestinal tract and seen often in day-to-day practice. A total of 66 patients were randomly divided in three groups and treated with: A) Kalingadi Ghanavati, three vatis of 500 mg twice daily with takra, B) Tryushnadi Ghrita, 10 g twice daily before meal with lukewarm water and C) Combination of both the drugs for 14 days. An assessment was done on the basis of Rogabala, Dehabala, Agnibala, and Chetasabala. The study revealed that combination proved better results than those of individuals. PMID- 22048539 TI - A clinical study of Nirgundi Ghana Vati and Matra Basti in the management of Gridhrasi with special reference to sciatica. AB - Gridhrasi can be equated with sciatica, where pain, weakness, numbness, and other discomforts along the path of the sciatic nerve often accompanies low back pain. It is a common affliction of adults, costing billions of dollars in healthcare and resulting in more lost days of work than any other illness but the common cold. A herniated disc, spinal stenosis, piriformis syndrome, etc., can all cause sciatica. The treatment available for sciatica in modern medicine is not very satisfactory.The role of research in Ayurveda is to elucidate the underlying principles and to explain them in modern parameters. The present study was aimed at establishing clinically the effect of Nirgundi (Vitex negundo) Ghan Vati (dried water extract) alone as well as in combination with Matra Basti in the management of Gridhrasi. A total of 119 patients were registered for the study, out of which 102 patients completed the treatment: 52 patients in group A (Nirgundi Ghan Vati) and 50 in group B (Nirgundi Ghan Vati + Matra Basti). The results show that both treatments had an effect on Gridhrasi, but there was better relief of the signs and symptoms in group B. Matra Basti and Nirgundi Ghan Vati might both contribute to different extents in the recovery of the patient. PMID- 22048540 TI - Clinical evaluation of the efficacy of Khadiradi yoga avachoornana in Kachchu with special reference to genitoinguinal intertrigo. AB - Kachchu is a simple localized dermatological infection of the genitoinguinal region, which occurs because of unhygienic observance, and manifests in the form of inflammation followed by secondary bacterial or fungal infections that can be best correlated to genitoinguinal intertrigo. Even though it rarely causes systemic manifestations, its mere presence itself is disturbing because of intractable itching and pain. It may delay the proper healing of the episiotomy wound and may cause difficulty in walking because of severe pain. Candida powder is the highest selling medicine for the intertrigo, as the incidence of intertrigo is as high as 40% in some particular seasons. In the Ayurveda fraternity, there is no established preparation that can be preserved safely in all the epochs of life in females and which is easy to apply. After understanding the disease in the perspective of the ayurvedic and modern medicinal systems, Khadiradi yoga choorna - a new ayurvedic formulation - was prepared on the basis of stringent ayurvedic principles. Hence, an attempt has been made to study the efficacy of the khadiradi yoga avachurnana(1) in Kachchu, with special reference to genitoinguinal intertrigo in females. PMID- 22048541 TI - A clinical study to assess the efficacy of Triyushnadi Anjana in Kaphaja Abhishyanda with special reference to vernal keratoconjunctivitis. AB - Vernal keratoconjunctivitis / spring catarrh is a variety of exogenous allergic conjunctivitis, which is a very troublesome ocular disease of childhood and in the adolescent age group. The child suffers from intense itching, grittiness, discharge, redness, lacrimation, photophobia, and so on, thereby, decreasing his learning hours. The troublesome features are aggravated in the spring season / hot climate that lasts for years together and rarely persists after adolescence. Mast cell stabilizers, topical Nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids are the available treatment options that too with symptomatic relief and potential side effects, which limits the long-term use of these medicines. The clinical picture of vernal keratoconjunctivitis / spring catarrh is very similar to Kaphaja Abhishyanda, and Triyushnadi Anjana Bhaishajya Ratnavali (B.R.), and its treatment was clinically tried on the patients attending the Netra Roga OPD of the R.G. Government P.G. Ayurveda College Hospital at Paprola (H.P.). A proper protocol and performa was adopted with strict inclusion and exclusion criteria. In the first phase, a pilot study was conducted on 38 clinically diagnosed patients with vernal keratoconjunctivitis, and it gave 100% relief in photophobia, foreign body (FB) sensation, and lacrimation, with marked relief in other features. Encouraged by this pilot work, Triyushnadi Anjana (TA) and 2% sodium cromoglycate (mast cell stabilizer) eye drops in the second-phase clinical trial on 32 patients were tried clinically to evaluate the comparative efficacy. In the second clinical trial, the patients were randomly divided into two groups and Group I was given sodium cromoglycate 2% eye drops and Group II was given TA. The outcome of this study verified the results of the first phase pilot study, and on comparison of the results of the two groups in the second clinical study it was observed that the TA-treated group showed better results. Transient irritation in the eyes was reported by all patients after application of TA, which was relieved by keeping the eyes closed for a few minutes. None of the patients reported any adverse action of the trial drug. Thus, it can be concluded that TA is a safe, cost-effective, and potent Ayurvedic alternative in the treatment of vernal keratoconjunctivitis / spring catarrh. PMID- 22048542 TI - A clinical study on Akshitarpana and combination of Akshitarpana with Nasya therapy in Timira with special reference to myopia. AB - Myopia, commonly referred to as shortsightedness, is the most common eye disease in the world with substantial social, educational, and economic impact. Some of the clinical features of Timira can be correlated with myopia. An open randomized clinical trial was conducted to evaluate the role of Tarpana with and without Nasya in patients suffering from myopia. In total, 41 patients were registered in two groups, out of which 30 patients completed the treatment. In Group A, Tarpana with Mahatriphaladya Ghrita and in Group B, Nasya with Abhijita taila followed by Tarpana with Mahatriphaladya Ghrita was administered. After enrollment of the patients in the study, the cardinal signs and symptoms of Timira - myopia, that is, visual acuity, clinical refraction, were evaluated before and after the treatment. Comparatively, more relief in the signs and symptoms were found in the Nasya group followed by the Tarpana group. PMID- 22048543 TI - Effects of Ayurvedic treatment on forty-three patients of ulcerative colitis. AB - Ulcerative colitis is a chronic idiopathic inflammatory bowel disease with a relapsing nature. It is a very challenging disease affecting a patient during the most active period of his life i.e. 20 to 40 years of age. The main features are ano-rectal bleeding with increased frequency of bowel evacuation, general debility and with abnormal structural pathology in the descending colon, particularly sigmoid colon. In modern medical science, there is no permanent curative and safe treatment for this disease. This study can be helpful for reducing the need of steroids and surgical processes in the patients of ulcerative colitis. A clinical study of 43 patients of ulcerative colitis has been conducted at the O.P.D. (outdoor patient department) and I.P.D. (indoor patient department) of the P D Patel Ayurveda Hospital, Nadiad. They were given Udumbara kvatha basti with oral Ayurveda medicaments including Kutaj ghan vati, Udumbara kvatha, and combination of Musta, Nagakesara, Lodhra, Mukta panchamrut rasa for a one-month period. Results were analyzed statistically by using the 't' test. In this study, it was observed that the symptoms and signs, daily dose of steroids and other anti-inflammatory drugs were reduced by more than 75% with a highly significant result. The hemoglobin level was also increased. PMID- 22048544 TI - A comparative study of efficacy of Tugaksheeree [Curcuma angustifolia Roxb. and Maranta arundinacea Linn.] in management of Amlapitta. AB - Amlapitta is a disease caused by increase of Amla Guna of Pitta. Starch obtained from the rhizomes of two plants viz., Curcuma angustifolia Roxb. (Fam. Zingiberaceae) and Maranta arundinacea Linn. (Fam. Marantaceae) are used as Tugaksheeree. In the present clinical study, the efficacy of Tugaksheeree was studied on 67 patients of Amlapitta. A 0 total of 84 patients suffering from Amlapitta were selected from the O.P.D. and I.P.D. sections in the department of Dravyaguna, I.P.G.T. and R.A., Hospital, Jamnagar, and were randomly divided into two groups. Thirty four patients completed the treatment course in Group I, and 33 patients completed the treatment course in Group II. The efficacy of drug Tugaksheeree was studied through internal administration of the starches of C. angustifolia Roxb. (Fam. Zingiberaceae) in Group I and M. arundinacea Linn. (Fam. Marantaceae) in Group II with the dose of 4 g TID with water for 30 days. Both the drugs were found highly effective in treating Amlapitta. They significantly relieved the cardinal symptoms viz., Avipaka, Tikta-amlodgara, Daha, Shoola, Chhardi and the associated symptoms viz., Aruchi, Gaurava, Udaradhmana, Antrakujana, Vit bheda, Shiroruja, Angasada, and Trit. Statistically significant increase in body weight was noticed in both the groups. This may be because the drugs corrected the Agni and acted as Brihmana and Dhatupushtikara. Both the drugs did not produce any side effects. Therefore, both these drugs (C. angustifolia Roxb. and M. arundinacea Linn.) can be used as substitutes for each other. PMID- 22048545 TI - A study on Apabahuka (frozen shoulder) and its management by Laghumasha taila nasya. AB - Apabahuka is a disease that usually affects the Amsa sandhi (shoulder joint).It is produced by the Vata dosha. Even though the term Apabahuka is not mentioned in the nanatmaja Vata vyadhi, Acharya Sushruta and others have considered Apabahuka as a Vataja vikara. Amsa shosha (wasting of the shoulder) can be considered as the preliminary stage of the disease, where loss or dryness of sleshaka kapha from amsa sandhi occurs. For the present study, Marsha nasya with Laghumasa Taila was administered to 15 patients for seven days, and the following results were obtained. After treatment, 53.33% relief was found on Bahupraspandita hara, 26.66% on Shoola, 30.00% on Stambha, 60.00% on Atopa, and 37.50% on wasting of muscles. On the overall effect of therapy alone, one (6.60%) patient got marked improvement, eight (53.33%) got moderate improvement, four (26.66%) were improved, and two (13.33%) patients remained unchanged. PMID- 22048546 TI - Evaluation of immunomodulatory effect of Ranahamsa Rasayanaya - A Sri Lankan classical rasayana drug, on experimental animals. AB - Immunity plays a key role in maintaining the health of an individual. Therefore, the rational modulation of the immunity through psycho-neuro-endocrine-immune (PNI) axis is useful for the prevention as well as for the curing of the diseases. As immunomodulation is a parameter for evaluation of the rasayana effect of a drug, the same has been studied to assess the rasayana effect of Ranahamsa Rasayanaya (RR). Experimental models such as antibody formation against sheep red blood cells (SRBC) and cell mediated immunity (CMI) have been carried out befitting on Wistar strain albino rats to determine the immunomodulatory effect plus rasayana effect of RR. Statistically significant increase in body weight, nonsignificant increase in antibody formation against SRBC, highly significant decrease in CMI were observed in the treatment groups, when compared to the standard control group. These results show the probable immunomodulatory and anabolic activities of the test drug. Outcome of these studies validate the strong rasayana effect of the test drug claimed by the traditional practitioners of Sri Lanka. PMID- 22048547 TI - Experimental evaluation of Hingusauvarchaladi Ghrita and Saptavartita Hingusauvarchaladi Ghrita with special reference to their anticonvulsant activity. AB - Incidence of epilepsy is 0.3 to 0.5% in different populations throughout the world, and the prevalence of epilepsy has been estimated at 5 to 10 persons per 1000. Scanning of the Ayurvedic classics reveals that 90% of the formulations mentioned to have action on sajnavaha srotas are ghrita-based formulations. Ghrita because of its yogavahi guna, incorporates the qualities of the drugs added to it without losing its own qualities. In the present study Hingusauvarchaladi ghrita and saptavartita Hingusauvarchaladi ghrita have been selected, to prove their anticonvulsant activity experimentally on albino mice, by the chemoshock method. The observations recorded have been analyzed by one-way ANOVA followed by Scheffe's test, statistically. Saptavartita Hingusauvarchaladi ghrita has shown better anticonvulsant activity in comparison to Hingusauvarchaladi ghrita. PMID- 22048548 TI - A comparative pharmacological evaluation of Taila (oil) and Ghrita (ghee) prepared with Guduchi (Tinospora cordifolia). AB - Guduchi (Tinospora cordifolia wild miers) is a well-known medicinal plant, which is abundantly used in different ayurvedic formulations utilizing varieties of media. The drug has properties like Rasayana (rejuvenating property), Krimighna (anthelmintics), and Kushtghna (used in skin disorders), as described in ayurvedic literature. Taila (oil) and Ghrita (ghee) are used as media in Ayurvedic Sneha (oleaginous) formulations. Both the test drugs, Guduchi Taila and Ghrita, are prescribed in Vatrakta (gout) and also indicated for Kushtha (skin disorder). With all these details, the Guduchi Taila and Guduchi Ghrita samples, prepared by using Taila and Ghrita as media, have been subjected to comparative pharmacological investigations, to assess the impact of the media on the expression of pharmacological activity. The formulations have been evaluated for immunomodulation, anti-inflammatory, and anti-stress activities. Both the formulations have been found to be active in most of the experiments, however, with the change of media, their results vary at different levels. Taila prepared from Guduchi was found to have an immunostimulating activity. The formulation prepared with Ghrita exhibited an anti-stress effect with an immunosuppressing activity. PMID- 22048549 TI - Preparation and physicochemical analysis of Rasaka Bhasma. AB - Rasaka, which is one among the Maharasas, is an ore of zinc and has been used to extract Yashada in ancient times. It has a wide range of therapeutic applications, including in diseases like Prameha, Streeroga, and so on. The practice of Rasaka Bhasma preparation has declined with time due to various reasons. The present study aims to identify the genuine samples of Rasaka, prepare Rasaka Bhasma by subjecting it to Shodhana and Marana, and undertake a physiochemical analysis of the prepared Bhasma with an eye toward the standardization of Rasaka Bhasma. PMID- 22048550 TI - Standardization of Gaja Puta and Ardha Gaja Puta in the preparation of Vanga Bhasma. AB - The Vanga Bhasma is an important one amongst the metallic Bhasmas. Mainly Gaja Puta, Ardhagaja Puta and Laghu Puta have been described for Marana of Vanga. The medicines, which are prepared from Gaja Puta, are said to be the best ones (Mahagunavidhayaka). Gaja Puta is commonly used in the preparation of almost all the Bhasmas. There are a few references found in classics regarding Ardhagaja Puta, but not any reference regarding its detail description, therefore, the effort was made to standardize both the Putas with regard to Vanga Bhasma. In the present study, Vanga Bhasma was prepared by Gaja Puta and Ardhagaja Puta. For Marana of Vanga, it was found that the Ardhagaja Puta is more convenient than Gaja Puta with respect to color and particle size analysis of Bhasma after Jarana procedure of Vanga. PMID- 22048551 TI - A critical review of concept of aging in Ayurveda. AB - Ayurveda has a holistic approach toward all the miseries of man and aging is one of these. It is classified as one of the natural and Yapya (palliative) diseases. It is the process of becoming old and decaying. As age advances, several changes take place in the body, in the external appearance, in the condition of Dosha, Dhatu, Mala, Agni, Oja, and so on, as well as in the mental and cognitive functions. Elderly people are susceptible to several chronic diseases also. The problems of the elderly are becoming a matter of great concern as increased life expectancy due to better medical services and improved technology is resulting in an increasing population of the aged. By the year 2020, the World will have more than one billion people aged 60 and over, and more than two-thirds of them will be living in the developing countries. A major concern related to the rapid increase in the population of the aged is that there will be an increase in the prevalence of chronic diseases and disabilities, both being conditions that tend to accompany the aging process. This burden is increasing day by day. In the Ayurvedic texts, a comprehensive description has been given of aging. The aim of this conceptual article is to compile and re-evaluate the various principles related to different aspects of aging. PMID- 22048552 TI - A clinical review of different formulations of Vasa (Adhatoda vasica) on Tamaka Shwasa (asthma). AB - Vasa (Adhatoda vasica Linn.) is a well known and easily available drug in almost all the seasons. Easy availability of any drug gains popularity among physicians as well as pharmaceuticals and this is the reason why almost every Kalpana of Vasa is found described in the Ayurvedika text. The different dosage forms of Vasa like Kvatha, Avaleha, Sneha, and Sandhana have been used for the treatment of Shwasa Roga. A number of research studies have been performed on different formulations of Vasa and its effect on Shwasa Roga. Therefore, a review study has been carried out on the Vasa extract, Vasa Avaleha (prepared from Svarasa and Kvatha), Vasa Ghrita, Vasarishta, and Vasakasava on Shwasa Roga, to know which formulation is better. It was found in the review that Vasa Ghana, Vasa Ghrita (1), and Vasa Avaleha have shown good results on Tamaka Shwasa. PMID- 22048553 TI - Description of Mutra Pariksha (urine examination) in Atreya Virachita sara sangraha. AB - Atreya in his sara sangraha, after Nadi pariksha, described / elaborated in detail the mutra pariksha. Under this he appropriately described various precautions for urine examination, various characteristics of mutra vitiated by Tridosha, differentiation of urine of diseased & normal person characteristics of sama & nirama, mutra, characters, mutra of sadhya & Asadhya rogi characters of murta in jeerna & Ajeerna (indigestion) conditions etc. PMID- 22048554 TI - Risk and protective factors for suicidal ideation among Taiwanese adolescents. AB - BACKGROUND: : Suicide is the ninth leading cause of death in adolescents aged 15 19 years in Taiwan. Suicidal ideation is an important predictor of committing suicide among adolescents. OBJECTIVES: : The aim of this study was to examine the important risk factors, the protective factors, and the role of protective factors on the relationship of risk factors to suicidal ideation among Taiwanese adolescents aged 15-19 years. METHODS: : By adopting a cross-sectional study, senior high school students (n = 577) aged 15-19 years in southern Taiwan were recruited for this study. An anonymous self-reported questionnaire was used to collect demographic characteristics, risk factors, protective factors, and suicidal ideation of the sample. Hierarchical logistic regression was used to identify the important risk and protective factors and the interaction between risk and protective factors on suicidal ideation. RESULTS: : Nearly 18% (n = 101) of the participants reported having suicidal ideation during the past 12 months. Gender (female; odds ratio [OR] = 4.23), life stress (OR = 1.03), depression (OR = 3.44), peer suicidal ideation (OR = 4.15), and bullying victimization (OR = 1.81) were important risk factors of suicidal ideation among the targeted sample. In addition, self-esteem (OR = 0.92) and emotional adaptation (OR = 0.88) were important protective factors of suicidal ideation. Self-esteem and emotional adaptation were not used to moderate the negative effects of life stress, depression, perceived peer suicidal ideation, and bullying victimization on suicidal ideation. The final model explained 40.6% of the total variance in suicidal ideation and correctly predicted 86.1% of participants with suicidal ideation. DISCUSSION: : Suicidal ideation prevention programs should be targeted to female adolescents. School-based efforts that provide adolescents with self esteem enhancement, emotional regulation skills training, positive peer norms for life, coping skills for managing stress and depression, and antibullying programs might help reduce the suicidal ideation of adolescents. PMID- 22048555 TI - Characterizing the structure of operating room staffing using social network analysis. AB - BACKGROUND: : Very little research has been focused on the interdisciplinary staffing characteristics of the operating room team, an essential component of providing safe patient care in a high-risk setting. OBJECTIVES: : The aim of this study was to determine how the operating room staffing of two surgical specialties compares in terms of social network variables. METHODS: : Staffing data from all general and neurosurgical procedures performed at a large Midwestern hospital were analyzed using Social Network Analysis methods. Network variables include centrality, team coreness, and the core/periphery network structure. Multidimensional scaling, correlation, and descriptive statistics were used for the analysis. RESULTS: : The core/periphery network structure was characteristic of both surgical services. Team coreness, a measure of how often the team worked together, was associated with the length of the case (p < .001). Procedure start time predicts the team coreness measure, with cases starting later in the day less likely to be staffed with a high core team (p < .001). Registered nurses constitute the majority of core interdisciplinary team members in both groups. DISCUSSION: : Analysis of the core/periphery structure of specialty team staffing networks indicates that many procedures are staffed with individuals who are associated peripherally with the specialty. Registered nurses as core group members are in a position to take a leadership role in the communication of norms and process variations to noncore members. The effect of having late starting cases staffed with a lower core team should be studied further because it pertains to patient outcomes. Future work should strive to account for the complex and dynamic nature of team development. PMID- 22048556 TI - Psychometric testing of the decisional conflict scale: genetic testing hereditary breast and ovarian cancer. AB - BACKGROUND: : Hereditary breast and ovarian cancer (HBOC) syndrome is attributed mostly to mutations in the Breast Cancer 1 and Breast Cancer 2 genes (BRCA1/2). Mutation carriers of BRCA1/2 genes have significantly higher risk for developing breast cancer compared with the general population (55%-85% vs. 12%) and for developing ovarian cancer (20%-60% vs. 1.5%). The availability of genetic testing enables mutation carriers to make informed decisions about managing their cancer risk (e.g., risk-reducing surgery). However, uptake of testing for HBOC among high-risk individuals is low, indicating the need to better understand and measure the decisional conflict associated with this process. OBJECTIVE: : The aim of this study was to evaluate the reliability and validity of the modified Decisional Conflict Scale for use in decisions associated with genetic testing for HBOC. METHODS: : This cross-sectional cohort study, recruited women who pursued genetic testing for HBOC in two genetic risk assessment clinics affiliated with a large comprehensive cancer center and one of their female relatives who did not pursue testing. The final sample consisted of 342 women who completed all 16 items of the Decisional Conflict Scale. The psychometric properties of the scale were assessed using tests of reliability and validity, including face, content, construct, contrast, convergent, divergent, and predictive validity. RESULTS: : Factor analysis using principal axis factoring with oblimin rotation elicited a three-factor structure: (a) Lack of Knowledge About the Decision (alpha = .97), (b) Lack of Autonomy in Decision Making (alpha = .94), and (c) Lack of Confidence in Decision Making (alpha = .87). These factors explained 82% of the variance in decisional conflict about genetic testing. Cronbach's alpha coefficient was .96. DISCUSSION: : The instrument is an important tool for researchers and healthcare providers working with women at risk for HBOC who are deciding whether genetic testing is the right choice for them. PMID- 22048557 TI - Self-efficacy program to prevent osteoporosis among Chinese immigrants: a randomized controlled trial. AB - BACKGROUND: : Recent Chinese immigrants have a low bone mineral density and are at a great risk for developing osteoporosis. The majority of Chinese men and women of all ages have inadequate information about their risks for developing osteoporosis and are seldom involved in preventive activities. OBJECTIVES: : The aim of this study was to evaluate the preliminary effectiveness of an educational intervention based on the self-efficacy theory aimed at increasing the knowledge of osteoporosis and adoption of preventive behaviors, including regular exercise and osteoporosis medication adherence, designed for Chinese immigrants, aged 45 years or above, living in the United States. METHODS: : A randomized controlled trial was employed, using a repeated-measure design. Foreign-born Mandarin speaking Asians (n = 110) were recruited to the study, and 83 of them (mean age = 64.08 years, SD = 9.48 years) were assigned randomly to either the intervention group (n = 42) or the attention control group (n = 41). There were 63 (75.9%) women and 20 (24.1%) men. Data were collected at baseline and 2 weeks after the intervention. RESULTS: : The participants who received the intervention had statistically significant improvements (p < .05) at 2 weeks postintervention with respect to osteoporosis-related knowledge, self-efficacy for exercise, and osteoporosis medication adherence. Moreover, the participants in the treatment group spent more time on moderate exercise, had higher energy expenditure on exercise, and had more osteoporosis medication use at 2 weeks postintervention when compared with controls. DISCUSSION: : The intervention targeting Mandarin speaking immigrants was effective in increasing the knowledge of osteoporosis and improving the adoption of preventive behaviors. Future research is needed to explore the long-term effect of this intervention on bone health behavior. PMID- 22048558 TI - Barriers to meditation by gender and age among cancer family caregivers. AB - BACKGROUND: Despite solid basic science research supporting meditation's physiologic benefits, meditation remains a marginalized practice for many Westerners; observational and descriptive studies indicate a spectrum of barriers to meditation practice. OBJECTIVE: The aim of this study was to determine differences in barriers to meditation by gender and age. METHODS: A cross sectional survey study of 150 family caregivers to adults with cancer visiting an outpatient chemotherapy center in Connecticut was conducted. The primary outcome was the Determinants of Meditation Practice Inventory. Explanatory variables included demographic characteristics, Center for Epidemiologic Studies-Depression Scale, Big Five Inventory, and Caregiver Reaction Assessment. RESULTS: Participants included 98 women and 52 men. Age range was 18-84 years (M = 52.3 years). The highest frequency of barriers for both genders related to misconceptions about meditation. The total number of barriers to meditation did not significantly vary by gender (p = .10) nor age (p = .27). After adjusting for personality trait, reactions to caregiving, and emotional distress, gender (adjusted beta = 0.81, SE = 1.70, p = .63) and age (adjusted beta = 0.02, SE = 0.05, p = .67) still did not predict the number of barriers to meditation. Backward elimination in model building showed that personality trait and reactions to caregiving account for 32% of the variability in barriers. DISCUSSION: The total number of barriers to meditation was examined, and a difference was not found by age or gender. It is possible that differences by age and gender exist at the item level of evaluation but were not evident when evaluating total scores. Further study is needed with samples large enough to have statistical power for item-level analysis. PMID- 22048559 TI - Establishing treatment fidelity in a web-based behavioral intervention study. AB - BACKGROUND: : Treatment fidelity pertains to the methodological strategies used to monitor and enhance the reliability and validity of behavioral interventions. Approaches to establishing treatment fidelity in Web-based interventions differ from those used in interventions that are delivered in person. OBJECTIVE: : The aim of this study was to describe a methodology for ensuring treatment fidelity in a Web-based cognitive behavioral stress management intervention. METHODS: : The intervention Coping With Cancer Workbook, adapted for Web-based delivery from an in-person intervention, was tested in a randomized controlled trial with 123 breast cancer survivors. Strategies for ensuring treatment fidelity were implemented and assessed. RESULTS: : The National Institutes of Health Behavior Change Consortium Treatment Fidelity Guidelines were relevant to establishing treatment fidelity for the Web-based intervention. DISCUSSION: : Web-based delivery of behavioral interventions is both a strength and a threat to treatment fidelity. Investigators must be cognizant of the elements of treatment fidelity and implement strategies to monitor and improve the reliability and validity of Web-based interventions. PMID- 22048560 TI - Factors associated with sleep quality in pregnant women: a prospective observational study. AB - BACKGROUND: : Sleep disturbance is a significant health issue in pregnant women. Although previous studies contribute to an understanding of the multifactorial nature of pregnancy-related sleep disturbance, objective measures of sleep were not included, and so data may be subject to recall and potential participant self report bias. OBJECTIVE: : The aim of this study was to identify sociodemographic, lifestyle, and health-related factors associated with poor sleep quality in women during their third trimester of pregnancy. METHODS: : This prospective study included 30 nulliparous women who wore a wrist actigraph to objectively monitor sleep for 7 consecutive days and completed the Pittsburgh Sleep Quality Index. RESULTS: : Fifteen women (50%) had a Pittsburgh Sleep Quality Index global score of >5, indicating poor sleep quality. Mean actigraphic sleep efficiency was only 80.05% +/- 6.27%. There were significant differences (p < .01) in sleep offset time and total nocturnal sleep time between weekdays and weekends. Later sleep onset time was associated with poorer sleep, including longer sleep latency, and reduced total nocturnal sleep time and sleep efficiency. DISCUSSION: : Nulliparous women experience both objective and subjective sleep disturbances, and their sleep patterns differ between weekdays and weekends during their third trimester of pregnancy. Results suggest that maternal sleep pattern may be improved by maintaining a regular and earlier bedtime so women have more opportunity to obtain sufficient nocturnal sleep and improved sleep quality. PMID- 22048561 TI - Sharing a traumatic event: the experience of the listener and the storyteller within the dyad. AB - BACKGROUND: : Individuals who have experienced traumatic events often share their experiences in story form. This sharing has consequences for both storytellers and listeners. Understanding the experience of both members of the listener storyteller dyad is of value to nurses who are often the listener within the nurse-patient dyad. OBJECTIVE: : The aim of this study was to illuminate the experiences of the listener and the storyteller when a traumatic event is shared within the dyad. METHODS: : The phenomenon was explored using an interpretive phenomenological approach. Participants consisted of 12 dyads, each with a storyteller and a listener. The storytellers were individuals who had been involved in U.S. Airways Flight 1549 when it crash-landed in the Hudson River in January 2009. Each storyteller identified a listener who had listened to them share their story of this event, dubbed The Miracle on the Hudson. In-depth interviews were conducted with each storyteller and each listener. RESULTS: : Five essential themes emerged from the data: Theme 1, The Story Has a Purpose; Theme 2, The Story as a Whole May Continue to Change as Different Parts Are Revealed; Theme 3, The Story Is Experienced Physically, Mentally,Emotionally, and Spiritually; Theme 4, Imagining the "What" as well as the "What If"; and Theme 5, The Nature of the Relationship Colors the Experience of the Listener and the Storyteller. Roy's Adaptation Model of Nursing was found to be applicable to the findings of this study. DISCUSSION: : For the participants in this study, the experience of sharing a traumatic event involved facts, feelings, and images. The story evolved as it was remembered, told, and listened to in a nonlinear, multifaceted way. The listener and the storyteller collaborated, adapted, and responded physically, mentally, emotionally, and spiritually. PMID- 22048562 TI - Synthesis and optical characterizations of chain-like Si@SiSe2 nanowire heterostructures. AB - A new type of chain-like Si@SiSe(2) nanowire heterostructures has been successfully synthesized via a one-step Au-catalyzed chemical vapor deposition (CVD) route. The composition and microstructure of the achieved structures were investigated by scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscope (TEM) and micro-Raman spectroscopy. Optical characterization was investigated using a confocal photoluminescent system with an Ar(+) laser (488 nm) as the excitation source. The results reveal that these chain-like structures emit pronounced and broadband red light, even visible with the naked eye at room temperature. A self organization model was proposed to illustrate the formation of these heterostructures, and the photoluminescent properties were discussed in detail. These new Si-based nanostructures may be helpful for further study of the basic physical properties of SiSe(2) and will find interesting applications in nanophotonic technologies and devices. PMID- 22048563 TI - Sleep, vigilance, and thermosensitivity. AB - The regulation of sleep and wakefulness is well modeled with two underlying processes: a circadian and a homeostatic one. So far, the parameters and mechanisms of additional sleep-permissive and wake-promoting conditions have been largely overlooked. The present overview focuses on one of these conditions: the effect of skin temperature on the onset and maintenance of sleep, and alertness. Skin temperature is quite well suited to provide the brain with information on sleep-permissive and wake-promoting conditions because it changes with most if not all of them. Skin temperature changes with environmental heat and cold, but also with posture, environmental light, danger, nutritional status, pain, and stress. Its effect on the brain may thus moderate the efficacy by which the clock and homeostat manage to initiate or maintain sleep or wakefulness. The review provides a brief overview of the neuroanatomical pathways and physiological mechanisms by which skin temperature can affect the regulation of sleep and vigilance. In addition, current pitfalls and possibilities of practical applications for sleep enhancement are discussed, including the recent finding of impaired thermal comfort perception in insomniacs. PMID- 22048564 TI - On the influence of basis sets and quantum chemical methods on the prediction accuracy of COSMO-RS. AB - This paper examines how the accuracy of activity coefficients at infinite dilution calculated from the conductor-like screening model for real solvents (COSMO-RS) depends on the basis set and the quantum chemical method used. Activity coefficients at various temperatures serve as experimental parameters for optimising the COSMO-RS parameters. A modification of the electrostatic misfit term of the energy function of COSMO-RS is presented that leads to a slightly higher accuracy. COSMO-RS parameter sets for nine different systematically varied basis sets using the density functional theory with the BP86 functional show that at least a valence double-zeta basis set is necessary for good accuracy. Larger basis sets show no advantages. Investigations of eight different quantum chemical calculation methods using a valence triple-zeta basis set are documented. Hartree-Fock and local density approximations give relatively poor results. The gradient-corrected density functionals investigated and the B3LYP hybrid functional show practically identical accuracy. The most accurate parameterisation was obtained with MP2. PMID- 22048565 TI - Epigenetics. Layer by layer. PMID- 22048566 TI - The internal rotational barriers about NCalpha and CalphaC backbone bonds of polypeptides. AB - In many studies on the protein folding problem it is assumed that the internal rotational barriers about NC(alpha) and C(alpha)C backbone bonds in unfolded polypeptides are quite small, around 0.7 kcal/mol, of an order comparable to the energy of kT at normal temperature (where k is Boltzmann's constant and T is the temperature in K) and hence that rotations about these bonds occur almost freely. Here it is highlighted that such consideration is an unfortunate mistake. Approximate values for the rotational barriers of NC(alpha) and C(alpha)C bonds are suggested from computations of U(phi, psi) potential energy surface (PES) maps of a number of oligopeptides by a semiempirical method for conformational analysis. The proposed values are about 16 kcal/mol for NC(alpha) bonds and 6 kcal/mol for C(alpha)C bonds. The values of the same barriers estimated from some ab initio quantum-mechanical PES maps for several dipeptides available in literature are also highlighted. PMID- 22048567 TI - Effect of pH and temperature on the global compactness, structure, and activity of cellobiohydrolase Cel7A from Trichoderma harzianum. AB - Due to its elevated cellulolytic activity, the filamentous fungus Trichoderma harzianum (T. harzianum) has considerable potential in biomass hydrolysis application. Cellulases from Trichoderma reesei have been widely used in studies of cellulose breakdown. However, cellulases from T. harzianum are less-studied enzymes that have not been characterized biophysically and biochemically as yet. Here, we examined the effects of pH and temperature on the secondary and tertiary structures, compactness, and enzymatic activity of cellobiohydrolase Cel7A from T. harzianum (Th Cel7A) using a number of biophysical and biochemical techniques. Our results show that pH and temperature perturbations affect Th Cel7A stability by two different mechanisms. Variations in pH modify protonation of the enzyme residues, directly affecting its activity, while leading to structural destabilization only at extreme pH limits. Temperature, on the other hand, has direct influence on mobility, fold, and compactness of the enzyme, causing unfolding of Th Cel7A just above the optimum temperature limit. Finally, we demonstrated that incubation with cellobiose, the product of the reaction and a competitive inhibitor, significantly increased the thermal stability of Th Cel7A. Our studies might provide insights into understanding, at a molecular level, the interplay between structure and activity of Th Cel7A at different pH and temperature conditions. PMID- 22048568 TI - [Antipsychotic medications for bipolar I disorders. New atypical neuroleptic drug asenapine approved]. PMID- 22048569 TI - [Advance directives in patients with mental disorders. Scope, prerequisites for validity, and clinical implementation]. AB - Since 1 September 2009, advance directives are regulated by law in Germany. This article discusses ethical challenges of advance directives in patients with mental disorders. Besides concrete information on the preferred medical treatment in concrete clinical situations, the mental capacity of the patient at the time of issuing the directive is essential. The "Decisional Competence Assessment Tool for Psychiatric Advance Directives" and empirical studies from the USA on advance directives in patients with mental disorders and the assessment by the treating psychiatrists of these patient directives are discussed. Ethical conclusions are drawn for handling advance directives in psychiatric practice. PMID- 22048571 TI - Inherited proliferative oral disorder: a reductionist approach to proliferative verrucous leukoplakia. PMID- 22048570 TI - Sympathetic nervous system in obesity-related hypertension: mechanisms and clinical implications. AB - Obesity markedly increases the risk of hypertension and cardiovascular disease, which may be related to activation of the sympathetic nervous system (SNS). Sympathetic overactivity directly and indirectly contributes to blood pressure (BP) elevation in obesity, including stimulation of the renin-angiotensin aldosterone system (RAAS). The adipocyte-derived peptide leptin suppresses appetite, increases thermogenesis, but also raises SNS activity and BP. Obese individuals exhibit hyperleptinemia but are resistant to its appetite-suppressing actions. Interestingly, animal models of obesity exhibit preserved sympathoexcitatory and pressor actions of leptin, despite resistance to its anorexic and metabolic actions, suggesting selective leptin resistance. Disturbance of intracellular signaling at specific hypothalamic neural networks appears to underlie selective leptin resistance. Delineation of these pathways should lead to novel approaches to treatment. In the meantime, treatment of obesity-hypertension has relied on antihypertensive drugs. Although sympathetic blockade is mechanistically attractive in obesity-hypertension, in practice its effects are disappointing because of adverse metabolic effects and inferior outcomes. On the basis of subgroup analyses of obese patients in large randomized clinical trials, drugs such as diuretics and RAAS blockers appear superior in preventing cardiovascular events in obesity--hypertension. An underused alternative approach to obesity-hypertension is induction of weight loss, which reduces circulating leptin and insulin, partially reverses resistance to these hormones, decreases sympathetic activation and improves BP and other risk factors. Though weight loss induced by lifestyle is often modest and transient, carefully selected pharmacological weight loss therapies can produce substantial and sustained antihypertensive effects additive to lifestyle interventions. PMID- 22048572 TI - Increasing the prosthodontic awareness of an aging Indian rural population. AB - OBJECTIVE: The aged are prone to biological, social, and psychological problems, especially those residing in the rural areas. The rural aging population in contrast to their urban counterparts is illiterate, poor, and ignorant; cumulative is the fact that the youth are leaving rural areas for money and better opportunity to urban areas. An educational and motivational program to increase prosthodontic awareness was therefore undertaken and it was studied whether this translated into an increased demand for prosthodontic services. MATERIALS AND METHODS: The study area consisted of a group of six villages collectively known as "Sarora" situated in Lucknow, Uttar Pradesh, India. The study population was divided on the basis of age, sex, education, and economic status and comparisons were made in between these groups. Interview and clinical examination were the tools of the study. Data were collected before and after the educational program and was subjected to statistical analysis. RESULTS: The educational program led to more subjects adopting tooth brushing and neem twig chewing as a method of oral hygiene maintenance. The prosthodontic need fulfillment increased from 3.5% before the program to 13.6% after education and motivation. CONCLUSION: It was concluded that mobile dental clinics, dental camps, and prosthodontic outreach programs could be solutions to spread awareness and disseminate treatment. PMID- 22048573 TI - Dental perspective on biomedical waste and mercury management: a knowledge, attitude, and practice survey. AB - CONTEXT: Management of waste generated in any health-care facility is a critical issue as it poses a direct threat to human health as well as to the environment. The biomedical waste generated in the dental scenario includes sharps, used disposable items, infectious waste (blood-soaked cotton, gauze, etc.), hazardous waste (mercury, lead), and chemical waste (such as spent film developers, fixers, and disinfectants). A major concern in our field is management and disposal of mercury. AIMS: To obtain information about the knowledge, attitude, and practices of dental institutions and dental practitioners in the disposal of waste. SETTINGS AND DESIGN: A self-administered questionnaire, composed of 50 questions was designed. MATERIALS AND METHODS: The questionnaire was distributed among the participants, chosen randomly, including dental students, faculty from dental colleges and private practitioners in and around Delhi, India. STATISTICAL ANALYSIS USED: The percentage response for each question from all the participants was obtained and the data was calculated. RESULTS: Many dentists have knowledge about the waste management but they lack in the attitude and practice. CONCLUSIONS: There is need for education regarding hazards associated with improper waste disposal at all levels of dental personnel. It is imperative that waste should be segregated and disposed off in a safe manner to protect the environment as well as human health. PMID- 22048574 TI - Evaluation of buccolingual inclination of posterior teeth in different facial patterns using computed tomography. AB - BACKGROUND AND OBJECTIVE: Buccolingual inclination of teeth is an essential factor in establishing good occlusion. The objective of this study was to evaluate the buccolingual inclination of molar teeth in different vertical skeletal patterns by using computed tomography scans. MATERIALS AND METHODS: Coronal section of the jaws obtained from computed tomograms were used to measure the buccolingual inclination of the long axis of the molars relative to their skeletal base. Forty male adult individuals with class I dental occlusion were selected. They were classified as short (Group 1), average (Group II), and long faced (Group III) as per their skeletal patterns measured by GoGn-SN, FH-MP, Y axis and facial height index in cephalograms. STATISTICAL ANALYSIS: ANOVA and Tukey HSD tests were applied to calculate if there were any significant differences in the mean molar inclination between the groups. Pearson's coefficients of correlation were calculated between the facial parameters and tooth inclination. RESULTS: The differences in the mean molar inclination between the short, average, and long faced groups is significant for mandibular 1 st and 2 nd molars and maxillary 2 nd molars. CONCLUSION: Variations in mean molar inclination values are observed between short, average, and long faced groups. PMID- 22048575 TI - Awareness among Indian dentist regarding the role of physical activity in prevention of work related musculoskeletal disorders. AB - BACKGROUND: The prevalence of work-related musculoskeletal complaints in dentists is high and the past two decades have witnessed a sharp rise in the incidence of various disorders. The prevalence of musculoskeletal pain ranges between 64% and 93%. The most effected regions have been back and neck. Various studies have been done to record stress levels and health-related behaviors of dentists in other countries but limited data is available among the Indian dentists. MATERIALS AND METHODS: Therefore a questionnaire survey was carried out among 102 Indian dentists belonging to different fields having at least one musculoskeletal disorder in last 6 months. RESULTS: The total sample consists of 80 males and 22 females. Out of the 102 over 97 of dentists had sought medical advice for these disorders during the previous 06 months and 74 of them also consulted the physiotherapist for exercises and ergonomic advice. The number of sessions taken for regular physical exercises was minimum 6 till 44 the most. The percentage of improvement in symptoms varied between 20% and 80%. CONCLUSIONS: A significant direct correlation between the number of sessions taken for physical activity and the self-perceived improvement in the symptoms was found using the Pearson correlation test. The work-related musculoskeletal disorders among dentists not only decrease their efficiency but also is a major concern among them. Self awareness and benefits of regular exercise is the need of the hour. PMID- 22048576 TI - Comparative evaluation of formocresol and mineral trioxide aggregate as pulpotomy agents in deciduous teeth. AB - AIM: To evaluate and compare mineral trioxide aggregate (MTA) and formocresol as pulpotomy medicaments by clinical and radiographic assessments and to assess the histological features of both pulpotomy medicaments in deciduous teeth. MATERIALS AND METHODS: This study was performed on 100 mandibular deciduous molar teeth requiring pulpotomy treatment. Children between age four and six years were randomly selected and divided into formocresol or MTA group. The patients were recalled after 3, 6, 9, 12 months respectively and evaluated clinically and radiographically. Histological assessment was done on lower deciduous canine teeth, which were undergoing serial extraction for interceptive orthodontic purpose. Pulpotomy was done on four teeth with formocresol and another four teeth with MTA. The teeth were extracted after six months following pulpotomy procedure and histologically evaluated. Two freshly extracted carious teeth were taken as controls. RESULTS: Clinical and radiographic criteria were laid and Chi analysis revealed significant difference in mobility ( P<=0.05), periodontal ligament widening ( P<=0.01 level) and inter - radicular radiolucency ( P<=0.02 level) between two groups at the end of 12 months. Histologically, in MTA group, a layer of new dentine formation with less dentinal tubules at the pulpotomized site was found. In formocresol group, increased inflammatory cells, a zone of atrophy, were noted in radicular portion of pulp. CONCLUSION: MTA is superior to formocresol clinically, radiographically. Histological analysis showed better reparative ability with hard tissue barrier formation with MTA compared to formocresol. PMID- 22048577 TI - Assessment of combination techniques in enhancing the regenerative potential of tricalcium phosphate graft in treatment of infrabony periodontal defects. AB - AIMS: The purpose of the present study was to evaluate and compare the clinical outcome of infrabony defects following reconstructive surgery with the use of tricalcium phosphate (TCP) alone; TCP and citric acid (CA) root conditioning; and TCP, CA, and oxidized regenerated cellulose (ORC) membrane. MATERIALS AND METHODS: Thirty-nine systemically healthy subjects with vertical infrabony defect were initially selected based on intraoral periapical radiographs and clinical examination to record probing pocket depth (PPD) and clinical attachment level (CAL). Only 21 defects revealed two-walled configuration on surgical debridement. These defects were selected and randomly allotted to the study groups. Group 1 defects were treated with TCP, group 2 with TCP+CA, and group 3 with TCP+CA+ORC. PPD, CAL, defect depth (DD), and level of alveolar crest (AC) were evaluated at the time of initial surgery and after 6 months at surgical re-entry. These measurements were utilized to calculate PPD reduction, CAL gain, defect fill (DF), %defect fill (%DF), and crestal resorption (CR). STATISTICAL ANALYSIS: A paired t-test was used for assessing changes in each group. Unpaired t-test was used for intergroup comparisons. RESULTS: All three groups showed statistically significant PPD reduction, CAL gain, DF, and %DF, but insignificant CR at the end of 6 months. On intergroup comparison, no statistically significant differences were noted between the groups for all the parameters. CONCLUSION: Efficacy of combination techniques using TCP+CA; TCP+CA+ORC in treatment of periodontal infrabony defects is at least equal to that of TCP alone. PMID- 22048578 TI - Prevalence of dental diseases in 5- to 14-year-old school children in rural areas of the Barabanki district, Uttar Pradesh, India. AB - BACKGROUND: Epidemiological studies are helpful in planning and implementing oral health programs in a given population. This initiative is a consequence of the absence of any information on any study being conducted in the past on the prevalence of dental diseases in the Barabanki district of Uttar Pradesh (UP). AIMS: The aims were to (1) assess the prevalence of gingivitis, fluorosis, and malocclusion in the school-going children of rural areas of district Barabanki and (2) evaluate the pattern of above-mentioned diseases in different age groups and genders. MATERIALS AND METHODS: A total of 836 school-going children comprising 430 boys and 406 girls were examined. A total of 238 children were in the age group of 5-7 years. A total of 277 and 321 children were in the age groups of 8-10 and 11-14 years, respectively. STATISTICAL ANALYSIS: A chi-square test was used for deriving results. RESULTS: The prevalence of gingivitis, fluorosis, and malocclusion was 78.35%, 33.37%, and 34.09%, respectively. The difference between age groups for the prevalence of gingivitis was highly significant, and was more among girls as compared to boys. A significant increase in the prevalence of malocclusion was observed with age. No significant difference was found among genders for the prevalence of malocclusion. An increase in the prevalence of fluorosis was highly significant with age. The difference in fluorosis was insignificant between boys and girls. PMID- 22048579 TI - Tobacco cessation and counseling: a dentists' perspective in Bhopal city, Madhya Pradesh. AB - INTRODUCTION: Dental team has high potential to help smokers to better oral/general health but to achieve this; they need to be clear about their role. Considering the importance of tobacco cessation, the authors carried out this study aimed at assessing the role, knowledge, current practices, different barriers, and tools to overcome the same as perceived by dentists in Bhopal city. MATERIALS AND METHODS: A self-administered structured, coded questionnaire was distributed to 200 private practitioners and the teaching staff in all the dental colleges in Bhopal city. RESULTS: Out of 200 dentists to whom questionnaire was administered, 168 responded within a week's time resulting in a high response rate of 84%. A total of 97% of the dentists agreed that it is the duty of every dentist to advice patients about tobacco cessation. A total of 58% strongly agree that formal training will be an effective tool to provide the guidelines to dentists in tobacco cessation and counseling. CONCLUSION: Monitoring of effective planning and execution of these programs by appropriate authorities at regular intervals is vital for successful achievement of the goal of "Tobacco Free Society." PMID- 22048580 TI - Analgesic efficacy of diazepam and placebo in patients with temporomandibular disorders: a double blind randomized clinical trial. AB - AIM: The aim of the study was to evaluate and compare the analgesic efficacy of placebo and diazepam in patients with temporomandibular disorder. MATERIALS AND METHODS: Thirty-five patients were recruited with a diagnosis of temporomandibular disorder based on standard clinical diagnostic criteria for temporomandibular disorder. The patients were put in to one of the two groups: placebo or diazepam at random. The average pain intensity was recorded with visual analog scale (VAS) at pretreatment, at weekly interval till the completion of a three-week trial and at post-treatment visit on the eighth week from baseline. The secondary outcome measures were changes in masticatory muscle tenderness, viz. massater muscle, lateral pterygoid muscle, medial pterygoid muscle and temporalis muscle and changes in mouth opening. STATISTICAL ANALYSIS: Intra-group comparison for analgesic efficacy and mouth opening was carried out by Wilcoxon's signed ranked test. Inter-group comparison for analgesic efficacy was also carried out using Mann-Whitney's test. RESULTS: A statistically significant (P<0.01) decrease in temporomandibular disorder pain in the placebo group (65%) and statistically highly significant (P<0.001) decrease in the diazepam group (72%) were observed on VAS after three weeks of treatment. The inter-group comparison demonstrated no statistically significant difference between the groups. CONCLUSION: This study suggests that the placebo can give near similar results as diazepam can. So the role of placebo should also be considered as one of the important management strategies. In the short term, reduction in the masticatory muscle tenderness and significant improvement in the mouth opening in both the groups were observed. PMID- 22048581 TI - Oral health status in relation to socioeconomic factors among the municipal employees of Mysore city. AB - AIM: To assess the prevalence of dental caries, periodontal diseases, oral pre malignant and malignant lesions in relation to socioeconomic factors among the municipal employees of Mysore city. SETTINGS AND DESIGN: The study was cross sectional in nature. MATERIALS AND METHODS: All the available employees (1187) during the study period were considered. World Health Organization (WHO) Oral Health Assessment form (1997) and a preformed questionnaire were used to collect the required data. Modified Kuppuswamy scale with readjustment of the per capita income to suit the present levels was used for classifying the individuals into different socioeconomic status (SES) categories. Data were collected by a single, trained and calibrated examiner (dentist) using mouth mirror and community periodontal index (CPI) probe under natural daylight. Data analysis was done using SPSS windows version 10. Quantitative data were analyzed using one-way analysis of variance (ANOVA) with Tukey's post hoc test and qualitative data were analyzed using chi-square or contingency coefficient. RESULTS: The age range of the study population was 19-57 years (mean 40.74 years, standard deviation 9.17). The prevalence of dental caries in the upper SES category was lesser (43.3%) compared to that in lower SES category (78.6%). 16.4% of the subjects in the upper category had a CPI score of 0 (healthy periodontium) and none of the subjects in the lower middle, upper lower and lower SES category had this score. The prevalence of oral pre-malignant and malignant lesions was higher in lower SES category (17.9%) than in upper class (0%). CONCLUSION: There was an inverse relationship between oral health status and SES. The overall treatment need was more in the lower class people than in the upper class. PMID- 22048582 TI - Role of ultrasound in detection of metastatic neck nodes in patients with oral cancer. AB - INTRODUCTION: Head and neck cancer is one of the most physically and emotionally devastating cancers and often leaves the patient disabled and disfigured. The presence of cervical metastasis is one of the factors that influence the outcome of the patients. Cervical lymph node metastasis plays an essential role in the treatment and prognosis of head and neck cancer patients. The assessment of the cervical lymph node status still remains an unsolved problem. We conducted a study to compare the diagnostic accuracy of clinical palpation and ultrasonogram (USG) in the detection of metastatic cervical nodes from oral squamous cell carcinoma patients. MATERIALS AND METHODS: Ten patients (age range, 45-63 years; mean age, 54 years) with squamous cell carcinoma in the head and neck region underwent clinical palpation and USG. The results of each modality were analyzed for sensitivity, specificity, positi ve predictive value, negative predictive value and accuracy. Pathologic analysis of the surgical resection served as the reference standard. RESULTS: USG yielded a sensitivity, specificity, positive, negative predictive value and accuracy as 85.7%, 90%, 92.3%, 81.8% and 87.5% whereas clinical palpation yielded a sensitivity, specificity, positive, negative predictive value and accuracy as 68.7%, 87.5%, 91.6%, 58.3% and 75%. CONCLUSION: USG is a reliable and valuable tool for metastatic lymph node screening in head and neck cancer patients. It is a cheap, noninvasive, easy-to-handle and cost effective diagnostic method. USG performed better than clinical palpation in detecting cervical metastatic nodes. PMID- 22048583 TI - Assessment of noise levels of the equipments used in the dental teaching institution, Bangalore. AB - CONTEXT: In dental practical classes, the acoustic environment is characterized by high noise levels in relation to other teaching areas, due to the exaggerated noise produced by some of these devices and use of dental equipment by many users at the same time. AIMS: To measure, analyze and compare noise levels of equipments among dental learning areas under different working conditions and also to measure and compare noise levels between used and brand new handpieces under different working conditions. MATERIALS AND METHODS: Noise levels were measured and analyzed in different dental learning areas that included clinical, pre-clinical areas and laboratories selected as representatives of a variety of learning-teaching activities. The noise levels were determined using a precision noise level meter (CENTER(r) 325 IEC 651 TYPE II) with a microphone. The mean of the maxima was determined. The data were collected, tabulated, and statistically analyzed using t tests. RESULTS: The noise levels measured varied between 64 and 97 dB(A).The differences in sound levels when the equipment was merely turned on and during cutting operations and also between used and brand new equipments were recorded. The laboratory engines had the highest noise levels, whereas the noise levels in high-speed turbine handpieces and the low-speed contra angle handpieces were decreased. CONCLUSION: The noise levels detected in this study are considered to be close to the limit of risk of hearing loss. PMID- 22048584 TI - Bond strength of composite-resin and resin-modified glass ionomer to bleached enamel: delay bonding versus an antioxidant agent. AB - OBJECTIVES: As enamel bond strength of the resin-modified materials is reduced after bleaching, a delay bonding of at least 1 week is recommended. This study investigated the efficacy of 10% sodium ascorbate hydrogel on the bond strength of bleached enamel as an antioxidant agent. MATERIALS AND METHODS: Ninety-six human, sound molars divided into eight groups. Buccal enamel surfaces of specimens in two negative control groups after preparation were bonded by the Z100 CR using the single-bond adhesive and Vitremer RmGI. Specimens in other groups after enamel preparation were bleached with 9.5% hydrogen peroxide. In two positive control groups, bonding of CR and RmGI was performed immediately after bleaching. Specimens in two other groups were immersed in distilled water after bleaching, and then CR and RmGI were bonded after 1 week. In last two groups, 10% sodium ascorbate hydrogel was applied after bleaching, and then they were bonded by CR and RmGI. The specimens were placed under shear force. STATISTICS: ANOVA and Duncan's multiple range tests were used for data analysis. RESULTS: Application of 10% sodium ascorbate hydrogel immediately before bonding and delay bonding for 1 week eliminated the negative effects of bleaching on CR and RmGI enamel bond strength. CONCLUSION: Application of 10% sodium ascorbate hydrogel or 1 week period elapsed after bleaching could significantly increase the enamel bond strength to a normal value. PMID- 22048585 TI - Need of implant dentistry at undergraduate dental curriculum in Indian dental colleges. AB - Edentulism is the major problem in the developing countries, and is widely spread in the current population, although the prevalence is declining and incidence of tooth loss is decreasing in the developed nations. The prevalence of edentulism in India varies from 60% to 69% of 25 years and above age group. It is obvious that the number of lost teeth increases with age leading to an increase in prevalence of partially edentulous patients. From a biological point of view, the replacement of a single missing tooth with an implant rather than a three-unit fixed partial denture, and the implant-supported complete denture has been proved more efficient in improving the mastication and maintaining the bone for a longer time and also more cost-effective treatment. Many dental schools throughout Europe and America have to a various extent introduced implant dentistry as part of the compulsory undergraduate curriculum. Thus, it becomes more essential to introduce implant dentistry at undergraduate level in Indian dental schools to manage the higher percentage of edentulism. PMID- 22048586 TI - Application of Botulinum toxin type A: an arsenal in dentistry. AB - An extremely effective way of preventing damage to and enhancing treatment of dental hard tissues and restorations would be to ''de-programme'' the muscles responsible for excessive destructive forces and other gnathological-related diseases. The new paradigm is the intramuscular injection of Botulinum toxin type A (BOTOX) into the affected muscles. It is a natural protein produced by anaerobic bacterium, Clostridium botulinum. The toxin inhibits the release of acetylcholine (ACH), a neurotransmitter responsible for the activation of muscle contraction and glandular secretion, and its administration results in reduction of tone in the injected muscle. There are seven distinct serotypes of Botulinum toxin, viz., A, B, C, D, E, F, and G, which differ in their potency, duration of action, and cellular target sites. This paper describes the different applications of BOTOX in dentistry. PMID- 22048587 TI - Failures in implants. AB - The burning problem that all the implantologists are confronted today is the complications and failures occurring with the treatment of osseointegrated implants. To further optimize the treatment outcome, etiologies and factors associated with implant failures should be elucidated. Conceivably such knowledge is needed for developing adequate treatment and prevention strategies. Hence, this paper is intended to provide an insight regarding various aspects of failures that affect dental implants. PMID- 22048588 TI - Orofacial manifestations of hematological disorders: anemia and hemostatic disorders. AB - The aim of this paper is to review the literature and identify orofacial manifestations of hematological diseases, with particular reference to anemias and disorders of hemostasis. A computerized literature search using MEDLINE was conducted for published articles on orofacial manifestations of hematological diseases, with emphasis on anemia. Mesh phrases used in the search were: oral diseases AND anaemia; orofacial diseases AND anaemia; orofacial lesions AND anaemia; orofacial manifestations AND disorders of haemostasis. The Boolean operator "AND" was used to combine and narrow the searches. Anemic disorders associated with orofacial signs and symptoms include iron deficiency anemia, Plummer-Vinson syndrome, megaloblastic anemia, sickle cell anemia, thalassaemia and aplastic anemia. The manifestations include conjunctiva and facial pallor, atrophic glossitis, angular stomatitis, dysphagia, magenta tongue, midfacial overgrowth, osteoclerosis, osteomyelitis and paraesthesia/anesthesia of the mental nerve. Orofacial petechiae, conjunctivae hemorrhage, nose-bleeding, spontaneous and post-traumatic gingival hemorrhage and prolonged post-extraction bleeding are common orofacial manifestations of inherited hemostatic disorders such as von Willebrand's disease and hemophilia. A wide array of anemic and hemostatic disorders encountered in internal medicine has manifestations in the oral cavity and the facial region. Most of these manifestations are non-specific, but should alert the hematologist and the dental surgeon to the possibilities of a concurrent disease of hemopoiesis or hemostasis or a latent one that may subsequently manifest itself. PMID- 22048589 TI - Validation of implant stability: a measure of implant permanence. AB - Implant stability is a requisite characteristic of osseointegration. Without it, long-term success cannot be achieved. Continuous monitoring in a quantitative and objective manner is important to determine the status of implant stability. Measurement of implant stability is a valuable tool for making decisions pertaining to treatment protocol and also improves dentist-patient communication. Owing to the invasive nature of histological analysis, various others methods have been proposed like radiographs, cutting torque resistance, reverse torque, modal analysis, resonance frequency analysis and Implatest(r) . This review focuses on objectives and various methods to evaluate implant stability. PMID- 22048590 TI - Concomitant hypo-hyperdontia with dens invaginatus. AB - Although developmental anomalies of tooth number are quite common in permanent dentition, concomitant occurrence of hypohyperdontia is a very rare mixed numeric anomalous condition of teeth. Very few cases of this condition have been reported in the English literature. Here we report such a rare case noted in a 26 year-old male dental graduate with no other associated systemic condition or syndrome. PMID- 22048591 TI - Treatment of oral submucous fibrosis with ErCr: YSGG laser. AB - Oral submucous fibrosis (OSMF) is one of the most poorly understood and unsatisfactorily treated diseases. Various medical and surgical treatments have been used but with limited benefits. However, with advent of lasers, oral surgeons are provided with new modality for treating OSMF. This case report highlights the pioneering effort in treating a moderate case of bilateral OSMF with Erbium Chromium Yttrium Scandium Gallium Garnet (ErCr:YSGG) laser showing promising result during follow-up. PMID- 22048592 TI - Non-surgical management of a mutilated maxillary central incisor with open apex and large periapical lesion. AB - A 24-year-old female patient reported with a mutilated maxillary left central incisor. The coronal tooth structure remaining was very less, discolored, and brittle. She gave history of trauma about 15 years back when the tooth got fractured. An intraoral periapical radiograph revealed an open apex and a large periapical lesion. The case was managed successfully by conservative means using intracanal calcium hydroxide and mineral trioxide aggregate (MTA) apical barrier followed by a fiber post and a core. The final crown restored back esthetics and function. A 6-month follow-up demonstrated a clinically asymptomatic and adequately functional tooth, with radiological signs of healing. PMID- 22048593 TI - Two-step procedure for root coverage using a free gingival graft and a subepthelial connective tissue graft. AB - Gingival recession is a multifaceted problem, for which several treatment options are available. Both epithelized and subepithelial connective tissue grafts offer predictable solutions for the treatment of gingival recession.The case report involved a 30-year-old man with gingival recession of 8 mm on 41 (Miller's class II recession). Before surgery, full mouth scaling and polishing were performed. Recession height, width, probing depth, clinical attachment level (CAL), and width of the attached gingiva (WAG) were measured at the baseline, two months postoperatively, and six months postoperatively. Four weeks after scaling, the first step of increasing the width of the attached gingiva was carried out, using a free gingival graft. Two months after this step, the subepithelial connective tissue was harvested from the palate and placed in relation to 41, to cover the residual defect.Two months postoperatively, there was a 3 mm gain in WAG and 35% root coverage. Six months postoperatively there was a significant increase in WAG, CAL; and reduction in height and width of recession (root coverage achieved was 75%). These results suggested that this two-stage surgical procedure could be successful for root coverage in case of deep recession and lack of attached gingiva in the mandibular anterior region. PMID- 22048594 TI - Restoration of an atrophic eye socket with custom made eye prosthesis, utilizing digital photography. AB - Ocular defects may cause several ocular and orbital disorders, which require surgical intervention. These defects are psychologically disturbing for the patients, and therefore, they require immediate management and rehabilitation by a team of specialist. Ocular prosthesis may be either readymade (stock) or custom made. Fabrication of a custom ocular prosthesis allows for a range of variations during construction. The iris can also be custom made by ocular painting or by digital photography. The optimum cosmetic and functional results of a custom-made prosthesis enhance the patient's rehabilitation to a normal life style. This paper elaborates the technique for fabrication of a custom-made ocular prosthesis for an atrophic eye socket utilizing digital photography. PMID- 22048595 TI - Two-piece hollow bulb obturator. AB - There are various types of obturator fabrication achievable by prosthodontist. Maxillectomy, which is a term used by head and neck surgeons and prosthodontists to describe the partial or total removal of the maxilla in patients suffering from benign or malignant neoplasms is a defect for which to provide an effective obturator is a difficult task for the maxillofacial prosthodontist. Multidisciplinary treatment planning is essential to achieve adequate retention and function for the prosthesis. Speech is often unintelligible as a result of the marked defects in articulation and nasal resonance. This paper describes how to achieve the goal for esthetics and phonetics and also describes the fabrication of a hollow obturator by two piece method, which is simple and maybe used as definitive obturator for maximum comfort of the patient. PMID- 22048596 TI - Gingival fibromatosis with hemi-osseous hyperplasia of jaws, focal maxillary viral papillomatosis of gingiva, fissured tongue and congenitally missing anterior teeth: a case report and surgical management of a new syndrome. AB - Gingival fibromatosis is characterized by fibrotic enlargement of the gingiva that can occur as inherited or sporadic form. Inherited form can be an isolated trait or as a component of a syndrome. This article reports a 35 year old male patient affected by gingival fibromatosis associated with hemiosseous hyperplasia of mandible, maxilla, and zygoma on the right side, viral papillomatosis of maxillary anterior gingiva, fissured tongue and congenitally missing anterior teeth. The patient was subjected to phase I and phase II periodontal therapy. There was no evidence of recurrence of the enlargement after one year but the papillomatosis recurred. Gingival fibromatosis has been reported to be associated with various other abnormalities but not with those described in our case. This observation raises the possibility that the coexistence of these entities in our case may represent a new syndrome. PMID- 22048597 TI - Comparison between five commonly used two-dimensional methods of human bite mark overlay production from the dental study casts. AB - AIM: The present study was conducted to determine the most accurate bite mark overlay fabrication technique by studying two physical characteristics, i.e., area and rotation of biting edges of anterior teeth of thirty volunteers. The objective of the study was to evaluate the reliability and efficacy of five commonly used methods of human bite mark overlays using two dimensional (2D) digital images of dental study casts as a gold standard, to rank different methods according to statistically based determination of relative accuracy of each method and to determine its feasibility in Forensic science. MATERIALS AND METHODS: Overlays were produced from the biting surfaces of six upper and six lower anterior teeth of 30 volunteers using the following five methods: a) hand tracing from study casts, b) hand tracing from wax impressions, c) xerographic method, d) radiopaque impression method and e) 2D computer-based method. Area of the biting edges of the anterior teeth and relative rotation of each anterior tooth were measured and compared. RESULTS: The xerographic method was determined to be the more accurate method with respect to tooth area and rotation. Hand tracing methods, from either wax impressions of teeth or directly from study casts, were determined to be inaccurate and subjective. CONCLUSIONS: It is recommended that forensic odontologists discontinue the use of hand tracing overlays in bite mark comparison cases as there is lot of scope for manipulation and observer bias. PMID- 22048598 TI - Quantitative assessment of expression of cell adhesion molecule (CD44) splice variants: CD44 standard (CD44s) and v5, v6 isoforms in oral leukoplakias: an immunohistochemical study. AB - AIM: The aim of this study was to semiquantitatively analyze the immunohistochemical expression pattern of CD44 standard (CD44s) and variant (CD44v) isoforms in leukoplakias using a panel of monoclonal antibodies recognizing epitopes of CD44s and of the variant exons v5 and v6. OBJECTIVE: To evaluate the efficacy of CD44s and CD44 v5, v6 immunoexpression as possible molecular markers in detecting high-risk leukoplakias when screening for this oral precancer. MATERIALS AND METHODS: Samples of oral leukoplakia (40 cases) and of normal mucosa (10 cases) were evaluated. Oral leukoplakia was graded into: hyperkeratosis without dysplastic change (8 cases), mild dysplasia (13 cases), moderate dysplasia (10 cases), and severe dysplasias (9 cases). Expression of CD44s,v5, v6 was analyzed by immunohistochemistry in a semiquantitative manner. Three areas of epithelium were scored B, S, and C, i.e., stratum basale, stratum corneum, and stratum spinosum, respectively in leukoplakias. Scoring of all specimens followed a two-parameter system, which implemented percentage of positive cells and staining intensities. Statistical analyses for each parameter of all groups and normals, mean, and standard deviation were calculated by using computer software package EPISTAT. RESULTS: In normal epithelium CD44s, CD44v5, and CD44v6 were expressed as membranous proteins localized on the surface of epithelial cells. Both basal and spinous layer of epithelia expressed strong positive staining of CD44s, v5, v6 which then gradually faded into the negative staining of the superficial keratin layer. Profile of CD44s and v5 revealed that the mean levels of stratum B, S, and C in normal cases were comparable to the study cases and by Student 't' test P>0.05 not significant. There was, however, a statistically significant decrease in the expression of v6 with increasing grades of dysplasias when compared with normal mucosa. CONCLUSION: Among CD44s and its variant isoforms,v5, v6, in this study, variant isoform v6 may serve as a marker in detecting high-risk leukoplakias. PMID- 22048599 TI - Questionnaire vs clinical surveys: the right choice?--A cross-sectional comparative study. AB - PURPOSE: To investigate the practical value of using questionnaires (self perceived assessment) as compared with clinical examinations (normative assessment) and to evaluate the role of socioeconomic status and implications of the results in understanding the public perception of oral health. MATERIALS AND METHODS: This was a cross-sectional single-blind study. A purposive sample of 860 bank employees of Belgaum city, India, were asked to fill in a close-ended questionnaire inquiring about their socioeconomic status, dental, periodontal health levels and treatment needs. Clinical examinations, employing the WHO dentition status and Community Periodontal Index, were performed to determine normative status and needs. Perceived and normative assessments were compared for sensitivity, specificity, positive and negative predictive values. RESULTS: The kappa values ranged from 0 (treatment needs) to 0.67 (for prosthesis). The degree of agreement with the following kappa values and sensitivity was seen in filled teeth (0.52, 60%), missing teeth (0.62, 83.8%), and prosthesis (0.67, 58.3%). However, the disagreement was seen with all other questions with average kappa value of 0.20. CONCLUSIONS: Self-assessment questionnaires were of low value in evaluating dental, periodontal health status and treatment needs in the study subjects. Findings reflect a low level of awareness that may influence care seeking behavior and socioeconomic status has a clear role to play in dental health perception. PMID- 22048600 TI - Comparative evaluation of marginal adaptation between nanocomposites and microhybrid composites exposed to two light cure units. AB - BACKGROUND: Recent advances in resin adhesives and restorative materials, as well as an increased demand for esthetics, have lead to the introduction of newer resin-based composites like nanocomposites and light-curing units like light emitting diodes (LEDs). AIM: The present study was conducted to evaluate the effect of conventional quartz tungsten halogen (QTH) curing unit and blue LED on marginal adaptation of microhybrid composite (Filtek Z250) and nanocomposite (Filtek Z350) resins. MATERIALS AND METHODS: Eighty Class V cavities were prepared on, extracted human premolars and were divided into four groups of 20 each. The four groups were designed according to the restorative resin and light cure unit used microhybrid/QTH, nanocomposites/QTH, microhybrid/LED and nanocomposites/LED. After thermocycling and immersion in 2% Basic Fuschin dye solution, the teeth were sectioned and dye penetration was observed under a stereomicroscope at 20X magnification. STATISTICAL ANALYSIS: All the samples were scored and results were analyzed using the "Kruskal Wallis and Mann Whitney tests" with "Wilcoxone correction." RESULTS: The results revealed least microleakage in microhybrid composites exposed to QTH and maximum in nanocomposites exposed to LED. CONCLUSION: Microhybrid composites exhibited lesser microleakage than nanocomposite resins. PMID- 22048601 TI - Tooth in the line of fracture: its prognosis and its effects on healing. AB - AIMS AND OBJECTIVE: The aim of this prospective study was to compare the postoperative results of mandibular angle fracture cases treated by open reduction and internal fixation wherein the third molar in the line of fracture was preserved in one group while it was extracted in the second group. MATERIALS AND METHODS: Group I consisted of 30 patients in which the mandibular third molar in the line of fracture was preserved and group II consisted of 24 patients in which it was extracted following specific criteria. Various parameters like postoperative healing, infection, occlusion, tooth vitality, and mobility were graded numerically. Statistical analysis using a t-test was done. Data were expressed as mean+/-SD and a probability (P) value of <0.05 was considered significant. RESULTS: The presence of infection with pain and tenderness was higher in group I. Osteogenesis was higher in group I till the end of the third week but the difference was not significant later. Discrepancy in occlusion was more in group II. Mobility of tooth decreased and status of periodontal tissue improved significantly with time. In the tooth involved, the return of vitality and decrease in pain/tenderness was significant after 1 week and continued till 24 weeks to normalcy. Two teeth showed mild root resorbtion and none showed ankylosis. CONCLUSION: Postoperative occlusal discrepancy is less but infection is higher when the tooth in the line of fracture is preserved as compared to when it is removed. More than half of the teeth in the fracture line show complete recovery within a period of 6 months to 1 year. Despite the risk of an increase in the rate of complications, the tooth in the line of fracture should be preserved for its merits. PMID- 22048602 TI - Bone allografts: a review of safety and efficacy. AB - Although bone allografts are being widely used in dentistry, many of clinicians appear to be unfamiliar with their preparation and processing as well as their use as safe and effective graft materials. The major concerns associated with these materials are antigenicity and risk of disease transmission from donor to recipient. To minimize this risk, the production of an allograft worthy of distribution and implantation requires strict attention to detail through a comprehensive process. With an increasing clinical requirement for bone grafting procedures, there is a commensurate increase in patients' demands for assurance that bank bone will not be infected with pathogens. To ensure the patients, dental surgeons should be able to cite factual information and recommendations by responsible organizations regarding safety of allografts. Knowledge of human bone allograft procurement, processing, and tracking may allow dentists to better educate patients and address concerns about this valuable treatment option. The purpose of this review is to furnish and update the current knowledge on processing, safety, and efficacy of allograft materials. PMID- 22048603 TI - A remarkable role of growth factors in resolving oral and specific periodontal pathologies: a strategic review. AB - The knowledge and the understanding of the role of growth factors, their mechanisms of action, and molecular signaling pathways, which have been reviewed in this article, suggest the potential for many novel therapeutic targets, not only for applying growth factors but also for the potential use of growth factor inhibitors or agents that target specific parts of the intracellular signaling pathways in controlling oral pathologies. There remains an enormous challenge to convert some of the knowledge from basic studies of bone cell physiology and inflammatory cells to therapeutically useful techniques for the future. PMID- 22048604 TI - Hemangiopericytoma - the need for a protocol-based treatment plan. AB - Hemangiopericytoma is a vascular tumor which comprises only 1% of all vascular tumors. The frequency of occurrence in the head and neck accounts for about 16 33% of all hemangiopericytomas. In this paper we discuss the surgical management, the difficulties in decision-making and treatment-planning in a case of a maxillary tumor in a five-year-old boy with a two-year follow-up. A five-year-old boy presented with a large unilateral maxillary tumor with nasal obstruction. Computed tomography revealed a heterogeneous mass completely occupying the right maxillary sinus and displacing the lateral wall of the nose and nasal septum. The lesion was diagnosed as hemangiopericytoma after histopathological confirmation. The option of surgical resection (total maxillectomy) was carried out after evaluating the available literature. Various treatment modalities like surgery, chemotherapy and radiotherapy were taken into consideration as the tumor has an aggressive nature. Due to the inadequate literature on definitive treatment options for these types of tumors, there was difficulty in arriving at a protocol based treatment plan. PMID- 22048605 TI - A comparative evaluation of healing with a computed tomography scan of bilateral periapical lesions treated with and without the use of platelet-rich plasma. AB - Periradicular surgery aims to achieve complete wound healing and regeneration of the periodontal unit. Platelet-rich plasma (PRP) is a platelet concentrate that is widely used to promote tissue healing, and bone induction through its various growth factors has been used in this study. This case report describes the use of PRP unilaterally in a bilateral periapical lesion in the same patient. The site treated with PRP showed better healing than the untreated site. This was confirmed with computed tomography (CT) scan readings. It was hypothesized that PRP could promote tissue regeneration and alveolar bone repair. PMID- 22048606 TI - Natal teeth in an infant with congenital hypothyroidism. AB - Teeth erupting at birth are referred to as natal teeth. It is a common and benign finding in the neonatal period. However, they may be associated with genetic syndromes like Ellis Van Creveld syndrome and Hallermann-Streiff syndrome. We report here a case of natal teeth in an infant with congenital hypothyroidism. PMID- 22048607 TI - A549 and PLC/PRF/5 cells can support the efficient propagation of swine and wild boar hepatitis E virus (HEV) strains: demonstration of HEV infectivity of porcine liver sold as food. AB - Recent evidence has indicated the cross-species transmission of hepatitis E virus (HEV) from pigs and wild boars to humans, causing zoonosis, mostly via consumption of uncooked or undercooked animal meat/viscera. However, no efficient cell culture system for swine and boar HEV strains has been established. We inoculated A549 cells with 12 swine and boar HEV strains of liver, feces, or serum origin at an HEV load of >=2.0 * 10(4) copies per well and found that the HEV progeny replicated as efficiently as human HEV strains, with a maximum load of ~10(8) copies/ml. However, the HEV load in the culture medium at 30 days post inoculation differed markedly by inoculum, ranging from 1.0 * 10(2) to 1.1 * 10(7) copies/ml upon inoculation at a lower load of approximately 10(5) copies per well. All progeny were passaged successfully onto A549 and PLC/PRF/5 cells. In sharp contrast, no progeny viruses were detectable in the culture supernatant upon inoculation with 13 swine and boar HEV strains at an HEV load of <1.8 * 10(4) copies per well. The present study also demonstrates that swine liver sold as food can be infectious, supporting the risk of zoonotic food-borne HEV infection. PMID- 22048609 TI - Formation of a cationic alkylidene complex via formal hydride abstraction: synthesis and structural characterization of [W(PMe3)4(eta2-CHPMe2)H]X (X = Br, I). AB - W(PMe(3))(4)(eta(2)-CH(2)PMe(2))H reacts with aryl halides to give the alkylidene complex, [W(PMe(3))(4)(eta(2)-CHPMe(2))H](+), which reacts with LiAlD(4) to give selectively W(PMe(3))(4)(eta(2)-CHDPMe(2))H, in which the deuterium resides in the methylene group; subsequent migration of deuterium from the methylene group provides a means to measure the rate constant for the formation of the 16 electron species [W(PMe(3))(5)] from W(PMe(3))(4)(eta(2)-CH(2)PMe(2))H. PMID- 22048610 TI - Introducing organosilicone source into the synthetic system of polyoxovanadates: two novel {V15Si6O48}-based extended chains. AB - Two novel extended chains based on rare {V(IV)(15)Si(6)O(48)} have been prepared under hydrothermal conditions by introducing an organosilicone source into the synthetic system of the polyoxovanadates. Single-crystal X-ray diffraction analyses show that the neighboring {V(IV)(15)Si(6)O(48)} clusters are linked by a pair of V(V)O(2) fragments via the coordination bonds of (Si-)O-V-O(-Si) to give rise to a zig-zag chain in compound 1, which is the first example of V(iv,v) mixed valence states successfully synthesized in {V(15)Si(6)O(48)}-containing POMs. While in 2 the linkages are changed to [Co(pdn)(2)(H(2)O)](2+) (pdn = 1,3 propanediamine) cations instead of {V(V)O(2)} fragments, to generate another comparable 1-D infinite chain, which demonstrates the first organic-inorganic vanadosilicon hybrid linked by a second transition-metal complex. The possible hydrolysis mechanism of tetraethyl orthosilicate as the Si source is postulated to afford a feasible protocol to synthesize a new type of vanadosilicate cluster. The magnetic properties of the two compounds have also been investigated. PMID- 22048612 TI - Interface-specific x-ray phase retrieval tomography of complex biological organs. AB - We demonstrate interface-specific propagation-based x-ray phase retrieval tomography of the thorax and brain of small animals. Our method utilizes a single propagation-based x-ray phase-contrast image per projection, under the assumptions of (i) partially coherent paraxial radiation, (ii) a static object whose refractive indices take on one of a series of distinct values at each point in space and (iii) the projection approximation. For the biological samples used here, there was a 9-200 fold improvement in the signal-to-noise ratio of the phase-retrieved tomograms over the conventional attenuation-contrast signal. The ability to 'digitally dissect' a biological specimen, using only a single phase contrast image per projection, will be useful for low-dose high-spatial resolution biomedical imaging of form and biological function in both healthy and diseased tissue. PMID- 22048611 TI - The association between extracoronary calcification and coronary artery disease in patients with type 2 diabetes mellitus. AB - Cardiovascular complications are the major cause of diabetes-associated morbidity and mortality. However, not all patients with diabetes are at increased risk for cardiovascular disease (CVD). Coronary artery calcification was found to be a powerful predictor of coronary artery disease (CAD). The presence of extracoronary cardiac calcification as a useful predictor of CAD is not yet established, especially in type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the relation between extracoronary calcification and extent of CAD in a group of T2DM patients who were scheduled for computed tomographic coronary angiography (CTCA). We prospectively studied 380 patients (151 had T2DM) under the age of 60 years who were scheduled for CTCA because of suspected CAD. Severity of CAD was assessed by Gensini score. Coronary artery calcium score (CACS) as well as calcium score in the aortic valve, mitral annulus, ascending aorta, and descending aorta were measured by a 256-row multidetector computed tomography scanner with dedicated software for calcium calculation. Patients with known CAD were excluded. Diabetic and nondiabetic patients had comparable age and gender distribution. However, the diabetic group had higher Gensini score, CACS, and extracoronary calcium score (ECCS). Logistic regression analyses identified male gender and ECCS as significant predictors for the presence of CAD in diabetic patients. Age, smoking, and ECCS were the significant predictors of CAD in nondiabetic patients. Type 2 diabetic patients had increased coronary and extracoronary calcification. ECCS was found to be a significant predictor of CAD in diabetic and nondiabetic patients only when CACS was not taken into account. PMID- 22048614 TI - Why and how do systems react in thermally fluctuating environments? AB - Many chemical reactions, including those of biological importance, take place in thermally fluctuating environments. Compared to isolated systems, there arise markedly different features due to the effects of energy dissipation through friction and stochastic driving by random forces reflecting the fluctuation of the environment. Investigation of how robustly the system reacts under the influence of thermal fluctuation, and elucidating the role of thermal fluctuation in the reaction are significant subjects in the study of chemical reactions. In this article, we start with overviewing the generalized Langevin equation (GLE), which has long been used and continues to be a powerful tool to describe a system surrounded by a thermal environment. It has been also generalized further to treat a nonstationary environment, in which the conventional fluctuation dissipation theorem no longer holds. Then, within the framework of the Langevin equation we present a method recently developed to extract a new reaction coordinate that is decoupled from all the other coordinates in the region of a rank-one saddle linking the reactant and the product. The reaction coordinate is buried in nonlinear couplings among the original coordinates under the influence of stochastic random force. It was ensured that the sign of this new reaction coordinate (= a nonlinear functional of the original coordinates, velocities, friction, and random force) at any instant is sufficient to determine in which region, the reactant or the product, the system finally arrives. We also discuss how one can extend the method to extract such a coordinate from the GLE framework in stationary and nonstationary environments, where memory effects exist in dynamics of the reaction. PMID- 22048613 TI - Impaired attentional disengagement in older adults with useful field of view decline. AB - OBJECTIVES: Typical measures of the useful field of view (UFOV) involve many components of attention. The objective of the current research was to examine the attentional operations that might underlie declines in the UFOV. METHOD AND RESULTS: We used 2 basic attention tasks to characterize the profile of visual attention in UFOV-impaired and -unimpaired observers. Our results suggested that declines in the UFOV result from a deficit in attentional disengagement, not a decrease in attentional breadth or scope. DISCUSSION: The results suggested that UFOV decline in normal aging can be associated with a specific attentional operation, namely attentional disengagement. These results suggest that the underlying cause of UFOV decline may not be a restriction in the breadth or scope of attention. Because the UFOV is a reliable predictor of driving safety, our results point to attentional components that are critical for the visual behavior of older adults. PMID- 22048615 TI - Structure identification and fermentation characteristics of pinoresinol diglucoside produced by Phomopsis sp. isolated from Eucommia ulmoides Oliv. AB - Pinoresinol diglucoside (PDG) is the important antihypertensive compound in Eucommia ulmoides Oliv., a traditional Chinese herb medicine. The research objective was to certify the possibility of producing PDG through fermentation. PDG-producing endophytic fungi were isolated from E. ulmoides Oliv., and the highest PDG-yielding (11.65 mg/L) isolate, XP-8, was identified as Phomopsis sp. according to the morphological characteristics and the phylogenetic tree constructed on the basis of the gene sequence in the internal transcribed spacers district. The microbial PDG was isolated by using S-8 resin and purified to a purity of 98.7% using preparative high-performance liquid chromatography (HPLC). Information obtained from the UV spectrum (277 and 227 nm, in water solution), infra-red spectrum (3,428; 2,930; 2,877; 1,637; 1,600; and 1,513; 1,460; 1,421; 1,269; 1,223; 1,075; 658 cm(-1), in powder), molecular weight (682 Da, measured using HPLC-electrospray ionization mass spectrometry (ESI/MS) and tandem mass spectrometry), and nuclear magnetic resonance analysis show the microbial PDG is (+)-1-pinoresinol 4,4'-di-O-beta-D-glucopyranoside, same as the plant-derived PDG. The microbial PDG is stable in pH range from 3 to 11 but less stable at temperature higher than 90 degrees C and in light exposure. During the fermentation, PDG production outside cells starts at the later stage of cell growth when the residual sugar in the medium was low. The study reveals the possibility for production of PDG by fermentation. PMID- 22048616 TI - Engineering of routes to heparin and related polysaccharides. AB - Anticoagulant heparin has been shown to possess important biological functions that vary according to its fine structure. Variability within heparin's structure occurs owing to its biosynthesis and animal tissue-based recovery and adds another dimension to its complex polymeric structure. The structural variations in chain length and sulfation patterns mediate its interaction with many heparin binding proteins, thereby eliciting complex biological responses. The advent of novel chemical and enzymatic approaches for polysaccharide synthesis coupled with high throughput combinatorial approaches for drug discovery have facilitated an increased effort to understand heparin's structure-activity relationships. An improved understanding would offer potential for new therapeutic development through the engineering of polysaccharides. Such a bioengineering approach requires the amalgamation of several different disciplines, including carbohydrate synthesis, applied enzymology, metabolic engineering, and process biochemistry. PMID- 22048617 TI - An erythromycin process improvement using the diethyl methylmalonate-responsive (Dmr) phenotype of the Saccharopolyspora erythraea mutB strain. AB - The Saccharopolyspora erythraea mutB knockout strain, FL2281, having a block in the methylmalonyl-CoA mutase reaction, was found to carry a diethyl methylmalonate-responsive (Dmr) phenotype in an oil-based fermentation medium. The Dmr phenotype confers the ability to increase erythromycin A (erythromycin) production from 250-300% when the oil-based medium is supplemented with 15 mM levels of this solvent. Lower concentrations of the solvent stimulated proportionately less erythromycin production, while higher concentrations had no additional benefit. Although the mutB strain is phenotypically a low-level erythromycin producer, diethyl methylmalonate supplementation allowed it to produce up to 30% more erythromycin than the wild-type (control) strain-a strain that does not show the Dmr phenotype. The Dmr phenotype represents a new class of strain improvement phenotype. A theory to explain the biochemical mechanism for the Dmr phenotype is proposed. Other phenotypes found to be associated with the mutB knockout were a growth defect and hyper-pigmentation, both of which were restored to normal by exposure to diethyl methylmalonate. Furthermore, mutB fermentations did not significantly metabolize soybean oil in the presence of diethyl methylmalonate. Finally, a novel method is proposed for the isolation of additional mutants with the Dmr phenotype. PMID- 22048618 TI - Smoking cessation treatment practices: recommendations for improved adoption on cardiology wards. AB - BACKGROUND AND OBJECTIVES: Smoking cessation treatment practices described by the 5 A's (ask, advise, assess, assist, arrange) are not well applied at cardiology wards because of various reasons, such as a lack of time and appropriate skills of the nursing staff. Therefore, a simplified guideline proposing an ask-advise refer (AAR) strategy was introduced in Dutch cardiac wards. This study aimed to identify factors that determine the intentions of cardiac ward heads in adopting the simplified AAR guideline, as ward heads are key decision makers in the adoption of new guidelines. Ward heads' perceptions of current smoking cessation practices at the cardiac ward were also investigated. METHODS: A cross-sectional survey with written questionnaires was conducted among heads of cardiology wards throughout the Netherlands, of whom 117 (64%) responded. RESULTS: According to the heads of cardiac wards, smoking cessation practices by cardiologists and nurses were mostly limited to brief practices that are easy to conduct. Only a minority offered intensive counseling or arranged follow-up contact. Heads with strong intentions of adopting the AAR guideline differed significantly on motivational and organizational attributes and perceived more smoking cessation assistance by other health professionals than did heads with weak intentions of adopting. Positive attitudes, social support toward adoption, and perception of much assistance at the ward were significantly associated with increased intentions to adopt the AAR guideline. CONCLUSIONS: Brief smoking cessation practices are adequately performed at cardiac wards, but the most effective practices, offering assistance and arranging for follow-up, are less than optimal. The AAR guideline offers a more feasible approach for busy cardiology wards. To ensure successful adoption of this guideline, the heads of cardiac wards should be convinced of its advantages and be encouraged by a supportive work environment. Policies may also facilitate the adoption of the AAR guideline. PMID- 22048619 TI - Supportive relationships, self-care confidence, and heart failure self-care. AB - BACKGROUND: The theory of heart failure (HF) self-care proposes that confidence mediates relationships between social support and self-care behaviors. OBJECTIVE: This study aimed to examine the effects of supportive relationships on self-care behaviors and the mediating effects of self-care confidence in HF outpatients. METHODS: Structural equation modeling (SAS version 9.1, SAS Institute Inc, Cary, North Carolina) was used to examine the influence of supportive relationships and self-care confidence on self-care management and maintenance in a cross-section of patients with HF (n = 97; age = 56 years; 57% men; 45% African American; 55% married). Models included 3 variables characterizing supportive relationships: marital status (1 = currently married, 0 = not currently married), social network size (number of persons available to provide support), and perceived social support (Medical Outcomes Study Social Support Scale). To account for the effects of severity of illness, 2 measures characterizing severity of HF were included: left ventricular ejection fraction and New York Heart Association functional classification of HF. The Self-Care of Heart Failure Index (version 4) was used to measure self-care confidence, management, and maintenance. A consensus of fit indices estimated overall model fit. RESULTS: Initial models fit the data; however, to improve fit and identify the most parsimonious models, 3 nonsignificant paths were removed, and modified models, including only social support and social network size, were proposed and tested. Modified models fit the data well and accounted for 15% in the variance in self-care maintenance (chi(2) P = .29) and 18% of the variance in self-care management (chi(2) P = .631). The indirect effect of social support (beta = 0.37; P = .0004) through self-care confidence (beta = 0.35; P = .0002) on self-care management, in the absence of a significant direct effect, supports the hypothesis that self-care confidence mediates the relationship between social support and self-care management. Social network size had a negative effect on self-care confidence (beta = -0.22; P = .029), but this effect was mediated by self-care confidence (beta = 0.33; P = .0002), which reduced the total negative effects. Self-care confidence was the best predictor of self-care management. In the self-care maintenance model, direct (beta = 0.27; P = .003) and indirect effects of social support (beta = 0.37; P = .0002) on self-care maintenance through self-care confidence (beta = 0.22; P = .001) attenuated negative effects of social network size (beta = -0.22; P = .0145). Social support was the best predictor of self care maintenance. CONCLUSIONS: Findings support the positive influence of social support on self-care behaviors. Self-care confidence mediated the relationship between social support and self-care behaviors and had direct influence on these behaviors as well. This suggests that self-care confidence and self-care behaviors can be enhanced by improving the quality of social support. PMID- 22048620 TI - A highly efficient kinetic resolution of Morita-Baylis-Hillman adducts achieved by N-Ar axially chiral Pd-complexes catalyzed asymmetric allylation. AB - Palladium complexes with an axially chiral N-Ar framework have been developed. These complexes showed high stereoselectivities in asymmetric allylic arylation to achieve the kinetic resolution of Morita-Baylis-Hillman adducts, affording up to 99% ee of (E)-allylation products and 92% ee of recovered Morita-Baylis Hillman adducts. PMID- 22048621 TI - Prevention: vitamin E leaves bitter aftertaste. PMID- 22048622 TI - Opinion: a personal note--40 years after the signing of the Cancer Act. PMID- 22048623 TI - Radiotherapy: stop recurring breast cancer nightmares. PMID- 22048624 TI - Carcinomas of an unknown primary origin--diagnosis and treatment. AB - Carcinomas of an unknown primary origin (CUP) account for 3-5% of all malignancies and are thus among the ten most-frequent cancers worldwide. Having a specific and unique phenotype of early and usually aggressive metastatic dissemination with no identifiable primary tumor, CUP are a challenge for physicians. The diagnostic workup of patients with CUP includes a careful clinical and extensive histopathological examination, as well as the use of imaging techniques. CUP can be divided into favorable and unfavorable subsets. Patients with unfavorable CUP subsets have a poor prognosis with a median survival of approximately 8 months; the optimal chemotherapy regimen for these patients remains to be determined. Although studies have focused on the introduction of new cytotoxic agents with broad-spectrum clinical activity (such as gemcitabine, irinotecan, and taxanes), no randomized trial has provided clear evidence of a survival benefit. Molecular targeted therapies that are approved for other solid tumors are now considered for the treatment of patients with CUP. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for 'lost' CUP origins. In this Review, we describe the clinical evaluation of patients with CUP, and discuss treatment strategies and outcomes of patients with various CUP subsets. PMID- 22048625 TI - Combination therapy: update on gastric cancer in East Asia. PMID- 22048626 TI - Medical oncology: clinical value of circulating tumor cells in breast cancer. PMID- 22048627 TI - Hematology: cast iron results for ESA use in cancer. PMID- 22048628 TI - The impact of therapeutic delay time on acute scintigraphic lesion and ultimate scar formation in children with first febrile UTI. AB - We assessed the role of therapeutic delay time (TDT) in acute renal cortical scintigraphic lesion (ASL) and ultimate scar formation (USF) in children with first febrile UTI and whether it is affected by the presence of vesico-ureteral reflux (VUR). 230 children, 90 girls and 140 boys with first febrile UTI were included. Radiologic (USG, DMSA, and VCUG), clinical (age, gender, peak fever, therapeutic delay time) and laboratory (CBC with differential count, ANC (absolute neutrophil count), BUN, Creatinine, urine analysis, gram stain, culture, CRP and ESR) variables were analysed. DMSA was performed within 5 days and after six months. VCUG was performed after acute phase of UTI. The differences in TDT according to the presence of ASL, USF and VUR were assessed. And the correlation between ASL or USF with the duration of TDT was assessed. Of 230 patients enrolled, 142 patients had refluxing UTI and 88 patients had non refluxing UTI. TDT was the risk factor associated with ASL and USF along with presence of VUR. TDT was longer in ASL positive group compared with the ASL negative group. Also USF group showed longer TDT compared with those without USF in both refluxing UTI and non refluxing UTI. The TDT was significantly shorter in USF group with the presence of VUR. Positive linear association was noted between prevalence of ASL and USF and duration of TDT. In conclusion, the impact of UTI on formation of USF may be enhanced by the presence of VUR with shorter duration of TDT. PMID- 22048630 TI - A pathway-based approach to identify molecular biomarkers in cancer. AB - Many examples highlight the power of gene expression profiles, or signatures, to provide an understanding of biological phenotypes. This is best seen in the context of cancer, where expression signatures have tremendous power to identify new cancer subtypes and to predict clinical outcomes. Gene expression profiles have been developed to personalize medicine, accurately predicting disease recurrence and tumor response to therapy. The use of these signatures as surrogate phenotypes allows us to link diverse experimental systems, which dissect the complexity of biological systems, with the in vivo setting in a way that was not previously feasible. Taken together, these new genomic tools provide the opportunity to develop rational strategies for treating the individual cancer patient. PMID- 22048631 TI - What is the best criterion for the interpretation of adrenal vein sample results in patients with primary hyperaldosteronism? AB - BACKGROUND: In patients with primary hyperaldosteronism, adrenal vein sampling (AVS) has emerged as a gold standard for distinguishing between unilateral and bilateral disease, but multiple criteria have been used and no consensus exists as to the most accurate criterion. The objective of this study was to determine which AVS criteria most accurately identify patients with unilateral surgical disease and are associated with significant clinical improvement after adrenalectomy. METHODS: This is a retrospective analysis of AVS results in 108 patients with primary hyperaldosteronism treated at a single institution. Literature review of AVS criteria was used to distinguish between unilateral and bilateral disease. RESULTS: Of the 10 AVS criteria identified in the literature, one criterion (ACTH stimulation, positioning: cortisol [adrenal]/cortisol [periphery] [Ca/Cp] > 5.0 and lateralization: aldosterone/cortisol [A/C] [dominant {D}]: A/C [nondominant {ND}] > 4:1) was the most accurate in identifying and correctly predicting lateralization of disease (P value range: < 0.001-0.0369). For this criterion, the true positive rate was 88%. The second most accurate criterion was no ACTH stimulation, positioning Ca/Cp > 1.1 and lateralization: A/C (D): A/C (ND) > 2:1. For this criterion, the overall true positive was 85%. However, we found no significant difference in clinical outcome based on individual criteria fulfillment. CONCLUSIONS: Of the multiple criteria used for AVS evaluation, one criterion has the best accuracy. With the increasing use of AVS, there should be a consensus by which these results are evaluated and surgeons recommend adrenalectomy. PMID- 22048632 TI - Diagnostic value of sentinel lymph node biopsy in gastric cancer: a meta analysis. AB - BACKGROUND: The possible application and validity of the sentinel lymph node (SLN) concept in gastric cancer (GC) is still debated. A systematic review to evaluate the diagnostic value of SLN biopsy (SLNB) in GC is urgently needed. METHODS: A systematic review of relevant literatures was performed in PubMed, Embase, and The Cochrane Library. A random-effect model was used to pool the data, and subgroup analysis was used to explain the heterogeneities. RESULTS: A total of 38 included studies (2,128 patients) were included. The pooled SLN identification rate, sensitivity, negative predictive value, and accuracy were 93.7% (95% confidence interval [95% CI]: 91.1-95.6%), 76.9% (95% CI: 71.6-81.4%), 90.3% (95% CI: 86.9-92.9%), and 92.0% (95% CI: 89.9-93.7%), respectively. Subgroup analysis showed that early T stage, combined tracers, submucosal injection method, conventional open surgery, and usage of immunohistochemistry were associated with higher SLN identification rate and sensitivity. CONCLUSIONS: SLNB in GC is technically feasible with an acceptable sensitivity. However, further studies are needed to confirm the best procedure and standard criteria. PMID- 22048633 TI - The combined expression of metaplasia biomarkers predicts the prognosis of gastric cancer. AB - BACKGROUND: Our previous study indicated that gene expression profiling of intestinal metaplasia (IM) or spasmolytic polypeptide-expressing metaplasia (SPEM) can identify useful prognostic markers of early-stage gastric cancer, and seven metaplasia biomarkers (MUC13, CDH17, OLFM4, KRT20, LGALS4, MUC5AC, and REG4) were selectively expressed in 17-50% of gastric cancer tissues. We investigated whether the combined expression of these metaplasia biomarkers could predict the prognosis of advanced stage gastric cancer. METHODS: The expression of seven metaplasia biomarkers was evaluated immunohistochemically using tissue microarrays comprised of 450 gastric cancer patients. The clinicopathologic correlations and the prognostic impact were analyzed according to the expression of multiple biomarkers. RESULTS: MUC13, CDH17, LGALS4, and REG4 were significant prognostic biomarkers in univariate analysis. No expression of four markers was found in 56 cases (14.2%); 1 marker was seen in 67 cases (17%), 2 in 106 cases (27%), 3 in 101 cases (25.7%), and 4 in 63 cases (16%). Patients in which two or fewer proteins were expressed (group B) showed younger age, undifferentiated or diffuse type cancer, larger tumor size, larger number of metastatic lymph nodes, and more advanced stage than those in which three or more proteins were expressed (group A). In undifferentiated or stage II/III gastric cancer, the prognosis of group B was significantly poorer than that of group A by multivariate analysis. CONCLUSIONS: The combined loss of expression of multiple metaplasia biomarkers is considered an independent prognostic indicator in undifferentiated or stage II/III gastric cancer. PMID- 22048635 TI - Morphology controllable growth of Pt nanoparticles/nanowires on carbon powders and its application as novel electro-catalyst for methanol oxidation. AB - Pt nanowires (PtNWs) have been controllably synthesized on carbon powders by the reduction of H(2)PtCl(6) with HCOOH. By adjusting the pH value of the solution, PtCl(6)(2-) can be controllable reduced into particles or nanowires. The Pt nanowires are single crystals growing along the <111> direction with a diameter of 3 nm and a length of 10 nm. The dispersion of Pt nanowires on the surface of carbon powders can be controlled by changing the loading of Pt. The PtNWs/C is evaluated as the catalyst for methanol oxidation. The PtNWs/C with 20 wt% Pt has a larger electrochemical active surface area and much higher mass activity for methanol oxidation than that of commercial Pt/C catalyst. The PtNWs/C catalyst shows significant improvement in the kinetics for methanol oxidation and mass transfer property due to the single crystal structure of the Pt nanowires. The PtNWs/C catalyst holds promising potential applications in energy converting devices and environmental protection. PMID- 22048636 TI - Reactions of cadmium(II) nitrate with 4-(trimethylammonio)benzenethiolate in the presence of N-donor ligands. AB - Reactions of Cd(NO(3))(2).4H(2)O with TabHPF(6) (TabH = 4 (trimethylammonio)benzenethiol) and Et(3)N in the presence of NH(4)SCN and five other N-donor ligands such as 2,2'-bipyridine (2,2'-bipy), phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (2,9-dmphen), 2,6-bis(pyrazd-3-yl)pyridine (bppy) and 2,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)pyridine (bdmppy) gave rise to a family of Cd(II)/thiolate complexes of N-donor ligands, {[Cd(2)(MU Tab)(4)(NCS)(2)](NO(3))(2).MeOH}(n) (1), [Cd(2)(MU-Tab)(2)(L)(4)](PF(6))(4) (2: L = 2,2'-bipy; 3: L = phen), [Cd(Tab)(2)(L)](PF(6))(2) (4: L = 2,9-dmphen; 5: L = bppy), and [Cd(2)(MU-Tab)(2)(Tab)(2)(bdmppy)](2)(PF(6))(8).H(2)O (6.H(2)O). These compounds were characterized by elemental analysis, IR spectra, UV-Vis spectra, (1)H NMR, electrospray ionization (ESI) mass spectra and single-crystal X-ray diffraction. For 1, each [Cd(NCS)](+) fragment is connected to its equivalents via a pair of Tab bridges to a one-dimensional chain. For 2 and 3, two [Cd(2,2' bipy)(2)](2+) or [Cd(phen)(2)](2+) units are linked by a pair of Tab bridges to form a cationic dimeric structure. The Cd atom in [Cd(Tab)(2)(L)](2+) dication of 4 or 5 is coordinated by two Tab ligands and chelated by two N atoms from 2,9 dmphen (4) or three N atoms from bppy (5), forming a distorted tetrahedral (4) or trigonal bipyramidal (5) coordination geometry. For 6, each of two [Cd(Tab)(bdmppy)] fragments is linked to one [(Tab)Cd(MU-Tab)(2)Cd(Tab)] fragment via two Tab bridges to generate a unique cationic zigzag tetrameric structure where the Cd centers take a tetrahedral or a trigonal bipyramidal coordination geometry. The results may provide an interesting insight into mimicking the coordination spheres of the Cd(II) sites of metallothioneins and their interactions with various N-donor ligands encountered in nature. PMID- 22048637 TI - Reconciling the bizarre inheritance of microtubules in complex (euglenid) microeukaryotes. AB - We introduce a hypothetical model that explains how surface microtubules in euglenids are generated, integrated and inherited with the flagellar apparatus from generation to generation. The Euglenida is a very diverse group of single celled eukaryotes unified by a complex cell surface called the "pellicle", consisting of proteinaceous strips that run along the longitudinal axis of the cell and articulate with one another along their lateral margins. The strips are positioned beneath the plasma membrane and are reinforced with subtending microtubules. Euglenids reproduce asexually, and the two daughter cells inherit pellicle strips and associate microtubules from the parent cell in a semi conservative pattern. In preparation for cell division, nascent pellicle strips develop from the anterior end of the cell and elongate toward the posterior end between two parent (mature) strips, so that the total number of pellicle strips and underlying microtubules is doubled in the predivisional cell. Each daughter cell inherits an alternating pattern of strips consisting of half of the nascent strips and half of the parent (mature) strips. This observation combined with the fact that the microtubules underlying the strips are linked to the flagellar apparatus created a cytoskeletal riddle: how do microtubules associated with an alternating pattern of nascent strips and mature strips maintain their physical relationship to the flagellar apparatus when the parent cell divides? The model of microtubular inheritance articulated here incorporates known patterns of cytoskeletal semi-conservatism and two new inferences: (1) a multigenerational "pellicle microtubule organizing center" (pMTOC) extends from the dorsal root of the flagellar apparatus, encircles the flagellar pocket, and underpins the microtubules of the pellicle; and (2) prior to cytokinesis, nascent pellicle microtubules fall within one of two "left/right" constellations that are linked to one of the two new dorsal basal bodies. PMID- 22048638 TI - The essence of student visual-spatial literacy and higher order thinking skills in undergraduate biology. AB - Science, engineering and mathematics-related disciplines have relied heavily on a researcher's ability to visualize phenomena under study and being able to link and superimpose various abstract and concrete representations including visual, spatial, and temporal. The spatial representations are especially important in all branches of biology (in developmental biology time becomes an important dimension), where 3D and often 4D representations are crucial for understanding the phenomena. By the time biology students get to undergraduate education, they are supposed to have acquired visual-spatial thinking skills, yet it has been documented that very few undergraduates and a small percentage of graduate students have had a chance to develop these skills to a sufficient degree. The current paper discusses the literature that highlights the essence of visual spatial thinking and the development of visual-spatial literacy, considers the application of the visual-spatial thinking to biology education, and proposes how modern technology can help to promote visual-spatial literacy and higher order thinking among undergraduate students of biology. PMID- 22048639 TI - Mapping and pyramiding of two major genes for resistance to the brown planthopper (Nilaparvata lugens [Stal]) in the rice cultivar ADR52. AB - The brown planthopper (BPH), Nilaparvata lugens (Stal), is one of the most serious and destructive pests of rice, and can be found throughout the rice growing areas of Asia. To date, more than 24 major BPH-resistance genes have been reported in several Oryza sativa ssp. indica cultivars and wild relatives. Here, we report the genetic basis of the high level of BPH resistance derived from an Indian rice cultivar, ADR52, which was previously identified as resistant to the whitebacked planthopper (Sogatella furcifera [Horvath]). An F(2) population derived from a cross between ADR52 and a susceptible cultivar, Taichung 65 (T65), was used for quantitative trait locus (QTL) analysis. Antibiosis testing showed that multiple loci controlled the high level of BPH resistance in this F(2) population. Further linkage analysis using backcross populations resulted in the identification of BPH-resistance (antibiosis) gene loci from ADR52. BPH25 co segregated with marker S00310 on the distal end of the short arm of chromosome 6, and BPH26 co-segregated with marker RM5479 on the long arm of chromosome 12. To characterize the virulence of the most recently migrated BPH strain in Japan, preliminary near-isogenic lines (pre-NILs) and a preliminary pyramided line (pre PYL) carrying BPH25 and BPH26 were evaluated. Although both pre-NILs were susceptible to the virulent BPH strain, the pre-PYL exhibited a high level of resistance. The pyramiding of resistance genes is therefore likely to be effective for increasing the durability of resistance against the new virulent BPH strain in Japan. PMID- 22048640 TI - Fine-mapping of qRfg2, a QTL for resistance to Gibberella stalk rot in maize. AB - Stalk rot is one of the most devastating diseases in maize worldwide. In our previous study, two QTLs, a major qRfg1 and a minor qRfg2, were identified in the resistant inbred line '1145' to confer resistance to Gibberella stalk rot. In the present study, we report on fine-mapping of the minor qRfg2 that is located on chromosome 1 and account for ~8.9% of the total phenotypic variation. A total of 22 markers were developed in the qRfg2 region to resolve recombinants. The progeny-test mapping strategy was developed to accurately determine the phenotypes of all recombinants for fine-mapping of the qRfg2 locus. This fine mapping process was performed from BC(4)F(1) to BC(8)F(1) generations to narrow down the qRfg2 locus into ~300 kb, flanked by the markers SSRZ319 and CAPSZ459. A predicted gene in the mapped region, coding for an auxin-regulated protein, is believed to be a candidate for qRfg2. The qRfg2 locus could steadily increase the resistance percentage by ~12% across different backcross generations, suggesting its usefulness in enhancing maize resistance against Gibberella stalk rot. PMID- 22048641 TI - Development of wild barley (Hordeum chilense)-derived DArT markers and their use into genetic and physical mapping. AB - Diversity arrays technology (DArT) genomic libraries were developed from H. chilense accessions to support robust genotyping of this species and a novel crop comprising H. chilense genome (e.g., tritordeums). Over 11,000 DArT clones were obtained using two complexity reduction methods. A subset of 2,209 DArT markers was identified on the arrays containing these clones as polymorphic between parents and segregating in a population of 92 recombinant inbred lines (RIL) developed from the cross between H. chilense accessions H1 and H7. Using the segregation data a high-density map of 1,503 cM was constructed with average inter-bin density of 2.33 cM. A subset of DArT markers was also mapped physically using a set of wheat-H. chilense chromosome addition lines. It allowed the unambiguous assignment of linkage groups to chromosomes. Four segregation distortion regions (SDRs) were found on the chromosomes 2H(ch), 3H(ch) and 5H(ch) in agreement with previous findings in barley. The new map improves the genome coverage of previous H. chilense maps. H. chilense-derived DArT markers will enable further genetic studies in ongoing projects on hybrid wheat, seed carotenoid content improvement or tritordeum breeding program. Besides, the genetic map reported here will be very useful as the basis to develop comparative genomics studies with barley and model species. PMID- 22048642 TI - The role of MAPK and Nrf2 pathways in ketanserin-elicited attenuation of cigarette smoke-induced IL-8 production in human bronchial epithelial cells. AB - Cigarette smoking is a major risk factor in chronic obstructive pulmonary disease (COPD) with chronic airway inflammation as a key feature. Blockade of serotonin receptor 2A (5-HTR(2A)) with ketanserin has been found to improve lung function in COPD patients. Furthermore, ketanserin has been shown to possess anti inflammatory properties in vivo. In this study, we investigated the antioxidative and anti-inflammatory properties of ketanserin and its underlying mechanism of action on cigarette smoke-induced interleukin (IL)-8 release in vitro. Primary normal human bronchial epithelial cells and human bronchial epithelial cell line (BEAS-2B) were treated with or without ketanserin prior to exposure to cigarette smoke medium (CSM). Exposure to CSM caused elevation of both mRNA and release of IL-8 with increased phosphorylation of p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2). Consistently, CSM-induced IL-8 release was blocked by SB203580, U0126, or MEK1 small interfering RNA (siRNA) but not SP600125. On the other hand, CSM caused a dose-dependent decrease in the ratio of reduced glutathione to oxidized glutathione (rGSH/GSSG) together with an increased translocation of Nrf2 to the nucleus demonstrated by Western blot analysis. Knock down of Nrf2 by siRNA completely blocked CSM-induced IL-8 release. Ketanserin suppressed CSM-induced IL-8 release by inhibiting p38, ERK1/2 MAPK, and Nrf2 signaling pathways and partially inhibited CSM-induced reduction of rGSH/GSSG ratio. Our data demonstrated the novel antioxidative and anti-inflammatory role of ketanserin via the Nrf2 signaling pathway in CSM-exposed human bronchial epithelial cells. This may open up new perspectives in the development of novel therapeutic targets in the treatment of cigarette smoke-related COPD. PMID- 22048643 TI - Aberrant expression of miR-638 contributes to benzo(a)pyrene-induced human cell transformation. AB - Identification of aberrant microRNA (miRNA) expression during chemical carcinogen induced cell transformation will lead to a better understanding of the substantial role of miRNAs in cancer development. To explore whether aberrant miRNAs expression can be used as biomarkers of chemical exposure in risk assessment of chemical carcinogenesis, we analyzed miRNA expression profiles of human bronchial epithelial cells expressing an oncogenic allele of H-Ras (HBER) at different stages of transformation induced by benzo(a)pyrene (BaP) by miRNA array. It revealed 12 miRNAs differentially expressed in HBER cells at both pretransformed and transformed stages. Differentially expressed miRNAs were confirmed in transformed cells and examined in 50 pairs of primary human non small-cell lung cancer (NSCLC) tissues using real-time PCR. Among these miRNAs, downregulation of miR-638 was found in 68% (34/50) of NSCLC tissues. However, the expression of miR-638 in HBER cells increased upon treatment of BaP in a dose dependent manner. The expression of miR-638 was also examined in peripheral lymphocytes from 86 polycyclic aromatic hydrocarbons (PAHs)-exposed (PE) workers. We found that the average expression level of miR-638 in peripheral lymphocytes from 86 PE workers increased by 72% compared with control group. The levels of miR-638 were correlated with the concentration of urinary 1-hydroxypyrene (1-OHP) and external levels of PAHs. Overexpression of miR-638 aggravated cell DNA damage induced by BaP, which might be mediated by suppression of breast cancer 1 (BRCA1), one of the target genes of miR-638. In summary, we suggest that miR-638 is involved in the BaP-induced carcinogenesis by targeting BRCA1. PMID- 22048644 TI - Cypermethrin induces astrocyte apoptosis by the disruption of the autocrine/paracrine mode of epidermal growth factor receptor signaling. AB - Cypermethrin is reported to affect astrocytes in rat brain; however, its mechanism of action is obscure. Here, we observed an increase in apoptosis in the cortical astrocytes upon treatment of rats with cypermethrin. We then characterized the mechanism governing the apoptosis. Because the epidermal growth factor receptor (EGFR) signaling regulates the survival of astrocytes, we investigated the effect of cypermethrin on EGFR activation. The astrocytes exhibited an early and irreversible attenuation in the basal EGFR phosphorylation. Supportively, molecular docking studies revealed considerable homology in the docking mode of cypermethrin and the known EGFR inhibitors, erlotinib and AG1478, to the kinase domain of EGFR. Furthermore, treatment with cypermethrin demonstrated a downregulation in the intracellular and secreted levels of heparin-binding epidermal growth factor (HB-EGF), an EGFR ligand. AG1478 reduced the synthesis of HB-EGF, suggesting the dependence of HB-EGF on EGFR activation. In addition, a neutralizing antibody against HB-EGF diminished the basal EGFR levels, indicating ligand-dependent expression of EGFR. Likewise, cypermethrin caused irreversible suppression in the basal EGFR levels, which induced apoptosis in astrocytes. The apoptosis was prevented by exogenous HB-EGF. These data imply an autocrine/paracrine mode of action of HB-EGF-EGFR in astrocyte survival. Consequently, cypermethrin induced a mitochondria-mediated apoptosis, characterized by rise in Bax/Bcl-2 ratio and cleavage of caspase-9, 3, and -7, and the effect was prevented by HB-EGF. HB-EGF activated the extracellular signal-regulated kinases and AKT pathways that protected against apoptosis. Together, these data demonstrate that cypermethrin induces astrocyte apoptosis by disrupting the autocrine/paracrine mode of HB-EGF-EGFR signaling at two levels, irreversible loss of basal EGFR and downregulation of HB-EGF. PMID- 22048645 TI - Exacerbation of acetaminophen hepatotoxicity by the anthelmentic drug fenbendazole. AB - Fenbendazole is a broad-spectrum anthelmintic drug widely used to prevent or treat nematode infections in laboratory rodent colonies. Potential interactions between fenbendazole and hepatotoxicants such as acetaminophen are unknown, and this was investigated in this study. Mice were fed a control diet or a diet containing fenbendazole (8-12 mg/kg/day) for 7 days prior to treatment with acetaminophen (300 mg/kg) or phosphate buffered saline. In mice fed a control diet, acetaminophen administration resulted in centrilobular hepatic necrosis and increases in serum transaminases, which were evident within 12 h. Acetaminophen induced hepatotoxicity was markedly increased in mice fed the fenbendazole containing diet, as measured histologically and by significant increases in serum transaminase levels. Moreover, in mice fed the fenbendazole-containing diet, but not the control diet, 63% mortality was observed within 24 h of acetaminophen administration. Fenbendazole by itself had no effect on liver histology or serum transaminases. To determine if exaggerated hepatotoxicity was due to alterations in acetaminophen metabolism, we analyzed sera for the presence of free acetaminophen and acetaminophen-glucuronide. We found that there were no differences in acetaminophen turnover. We also measured cytochrome P450 (cyp) 2e1, cyp3a, and cyp1a2 activity. Whereas fenbendazole had no effect on the activity of cyp2e1 or cyp3a, cyp1a2 was suppressed. A prolonged suppression of hepatic glutathione (GSH) was also observed in acetaminophen-treated mice fed the fenbendazole-containing diet when compared with the control diet. These data demonstrate that fenbendazole exacerbates the hepatotoxicity of acetaminophen, an effect that is related to persistent GSH depletion. These findings are novel and suggest a potential drug-drug interaction that should be considered in experimental protocols evaluating mechanisms of hepatotoxicity in rodent colonies treated with fenbendazole. PMID- 22048646 TI - Doxorubicin increases oxidative metabolism in HL-1 cardiomyocytes as shown by 13C metabolic flux analysis. AB - Doxorubicin (DXR), an anticancer drug, is limited in its use due to severe cardiotoxic effects. These effects are partly caused by disturbed myocardial energy metabolism. We analyzed the effects of therapeutically relevant but nontoxic DXR concentrations for their effects on metabolic fluxes, cell respiration, and intracellular ATP. (13)C isotope labeling studies using [U (13)C(6)]glucose, [1,2-(13)C(2)]glucose, and [U-(13)C(5)]glutamine were carried out on HL-1 cardiomyocytes exposed to 0.01 and 0.02 MUM DXR and compared with the untreated control. Metabolic fluxes were calculated by integrating production and uptake rates of extracellular metabolites (glucose, lactate, pyruvate, and amino acids) as well as (13)C-labeling in secreted lactate derived from the respective (13)C-labeled substrates into a metabolic network model. The investigated DXR concentrations (0.01 and 0.02 MUM) had no effect on cell viability and beating of the HL-1 cardiomyocytes. Glycolytic fluxes were significantly reduced in treated cells at tested DXR concentrations. Oxidative metabolism was significantly increased (higher glucose oxidation, oxidative decarboxylation, TCA cycle rates, and respiration) suggesting a more efficient use of glucose carbon. These changes were accompanied by decrease of intracellular ATP. We conclude that DXR in nanomolar range significantly changes central carbon metabolism in HL-1 cardiomyocytes, which results in a higher coupling of glycolysis and TCA cycle. The myocytes probably try to compensate for decreased intracellular ATP, which in turn may be the result of a loss of NADH electrons via either formation of reactive oxygen species or electron shunting. PMID- 22048647 TI - Dickkopf 1 mediates glucocorticoid-induced changes in human neural progenitor cell proliferation and differentiation. AB - Glucocorticoids (GC) are critical for normal development of the fetal brain, and alterations in their levels can induce neurotoxicity with detrimental consequences. Still, there is little information available on the effects of GC on human neural stem/progenitor cells (hNPC). In the present study, we have investigated the effects of the synthetic GC dexamethasone (Dex) on hNPC grown as neurospheres, with special focus on their proliferation and differentiation capacity and the underlying molecular mechanisms. Immunocytochemical stainings showed that Dex markedly decreases proliferation and neuronal differentiation while promoting glia cell formation. Analysis of pathway-specific genes revealed that Dex induces an upregulation of the Wnt-signaling antagonist DKK1. Moreover, Dex- or DKK1-treated hNPCs showed reduced transcriptional levels of the two canonical Wnt target genes cyclin D1 and inhibitor of DNA binding 2 (ID2). Chromatin immunoprecipitation showed that Dex, via the glucocorticoid receptor, interacts with the DKK1 promotor. Treatment of hNPC with recombinant DKK1 or neutralizing antibodies indicated that DKK1 has a critical role in the Dex induced inhibition of proliferation and neuronal differentiation with a concomitant increase in glial cells. Taken together, our findings show that GC reduce proliferation and interfere with differentiation of hNPCs via the canonical Wnt-signaling pathway. PMID- 22048649 TI - Centers and centroids of the cone-beam projection of a ball. AB - In geometric calibration of cone-beam (CB) scanners, point-like marker objects such as small balls are imaged to obtain positioning information from which the unknown geometric parameters are extracted. The procedure is sensitive to errors in the positioning information, and one source of error is a small bias which can occur in estimating the detector locations of the CB projections of the centers of the balls. We call these detector locations the center projections. In general, the CB projection of a ball of uniform density onto a flat detector forms an ellipse. Inside the ellipse lie the center projection M, the ellipse center C and the centroid G of the intensity values inside the ellipse. The center projection is invariably estimated from C or G which are much easier to extract directly from the data. In this work, we quantify the errors incurred in using C or G to estimate M. We prove mathematically that the points C, G, M and O are always distinct and lie on the major axis of the ellipse, where O is the detector origin, defined as the orthogonal projection of the cone vertex onto the detector. (The ellipse can only degenerate to a circle if the ball is along the direct line of sight to O, and in this case all four points coincide.) The points always lie in the same order: O, M, G, C which establishes that the centroid has less geometric bias than the ellipse center for estimating M. However, our numerical studies indicate that the centroid bias is only 20% less than the ellipse center bias so the benefit in using centroid estimates is not substantial. For the purposes of quantifying the bias in practice, we show that the ellipse center bias ||CM|| can be conveniently estimated by eA/(pi f(~) where A is the area of the elliptical projection, e is the eccentricity of the ellipse and f(~) is an estimate of the focal length of the system. Finally, we discuss how these results are affected by physical factors such as beam hardening, and indicate extensions to balls of non-uniform density. PMID- 22048648 TI - Smooth muscle proteins from Hirschsprung's disease facilitates stem cell differentiation. AB - BACKGROUND AND AIMS: The transplantation of neural crest derived stem cells (NCSC's) is a potent alternative for the treatment of Hirschsprung's disease (HSCR). Cells to be transplanted should find an appropriate microenvironment to survive and differentiate. To investigate the quality of this microenvironment, effects of HSCR-smooth-muscle-protein extracts upon NCSC's were studied in vitro. METHODS: Postnatal human gut from children undergoing colonic resection due to HSCR was divided in segments. Smooth muscle was dissected and homogenized. Glial cell-line-derived-neurotrophic-factor (GDNF) concentration was measured in the homogenates from the individual segment using ELISA. NCSC's were exposed to protein extracts derived from ganglionic and aganglionic HSCR segments, and their effect upon neurite outgrowth, survival and branching was evaluated. RESULTS: The amount of the factors varied considerably between the proximal and distal segments, and also from patient to patient. While extracts from proximal segments tended to have more prominent effects, all HSCR-muscle-protein extracts increased neuronal survival and network formation. CONCLUSION: Muscle protein from aganglionic bowel supports the survival and outgrowth of NCSC's and is so an appropriate target for neural stem cell treatment. PMID- 22048650 TI - Efficacy of hemivertebra resection for congenital scoliosis: a multicenter retrospective comparison of three surgical techniques. AB - STUDY DESIGN: Multicenter, retrospective study. OBJECTIVE: To compare the outcomes of three surgical treatments for congenital spinal deformity due to a hemivertebra. SUMMARY OF BACKGROUND DATA: Congenital anomalies of the spine can cause significant and progressive scoliosis and kyphosis. Their management may be challenging and controversy remains over the "best" surgical treatment. METHODS: A multicenter retrospective study of patients with congenital spinal deformity due to 1 or 2 level hemivertebra(e) was performed. The surgical treatments included hemiepiphysiodesis or in situ fusion (group 1), instrumented fusion without hemivertebra excision (group 2), or instrumented hemivertebra excision (group 3). RESULTS: Seventy-six patients with minimum 2-year follow-up were evaluated. The mean age was 8 years (range: 1-18). The hemivertebra were fully segmented, nonincarcerated (67%), incarcerated (1%), and semisegmented (32%). There were 65 patients with single hemivertebra and 11 patients with double hemivertebra. There were 14 (18.4%) group 1, 20 (26.3%) group 2, and 42 (55.3%) group 3 patients. Group 1 (37 +/- 14 degrees ) and group 3 (35 +/- 26 degrees ) patients had smaller preoperative curves than group 2 patients (55 +/- 26 degrees ) (P < 0.01). Group 3 had better percent correction at 2 years than groups 1 and 2 (P < 0.001). Group 3 had shorter fusion (P = 0.001), less estimated blood loss (EBL, P = 0.03), and a trend toward shorter operative times than group 2 (P = 0.10). The overall complication rate for the entire group was 30% group 1 (23%), group 2 (17%), and group 3 (44%) (P = 0.09). CONCLUSION: While hemivertebra resection for congenital scoliosis had a higher complication rate than either hemiepiphysiodesis/in situ fusion or instrumentated fusion without resection, posterior hemivertebra resection in younger patients resulted in better percent correction than the other two techniques. PMID- 22048651 TI - Comparative effectiveness evidence from the spine patient outcomes research trial: surgical versus nonoperative care for spinal stenosis, degenerative spondylolisthesis, and intervertebral disc herniation. AB - STUDY DESIGN: Cost-effectiveness analysis of a randomized plus observational cohort trial. OBJECTIVE: Analyze cost-effectiveness of Spine Patient Outcomes Research Trial data over 4 years comparing surgery with nonoperative care for three common diagnoses: spinal stenosis (SPS), degenerative spondylolisthesis (DS), and intervertebral disc herniation (IDH). SUMMARY OF BACKGROUND DATA: Spine surgery rates continue to rise in the United States, but the safety and economic value of these procedures remain uncertain. METHODS: Patients with image confirmed diagnoses were followed in randomized or observational cohorts with data on resource use, productivity, and EuroQol EQ-5D health state values measured at 6 weeks, 3, 6, 12, 24, 36, and 48 months. For each diagnosis, cost per quality-adjusted life year (QALY) gained in 2004 US dollars was estimated for surgery relative to nonoperative care using a societal perspective, with costs and QALYs discounted at 3% per year. RESULTS: Surgery was performed initially or during the 4-year follow-up among 414 of 634 (65.3%) SPS, 391 of 601 (65.1%) DS, and 789 of 1192 (66.2%) IDH patients. Surgery improved health, with persistent QALY differences observed through 4 years (SPS QALY gain 0.22; 95% confidence interval, CI: 0.15, 0.34; DS QALY gain 0.34, 95% CI: 0.30, 0.47; and IDH QALY gain 0.34, 95% CI: 0.31, 0.38). Costs per QALY gained decreased for SPS from $77,600 at 2 years to $59,400 (95% CI: $37,059, $125,162) at 4 years, for DS from $115,600 to $64,300 per QALY (95% CI: $32,864, $83,117), and for IDH from $34,355 to $20,600 per QALY (95% CI: $4,539, $33,088). CONCLUSION: Comparative effectiveness evidence for clearly defined diagnostic groups from Spine Patient Outcomes Research Trial shows good value for surgery compared with nonoperative care over 4 years. PMID- 22048652 TI - En bloc excisions of chordomas in the cervical spine: review of five consecutive cases with more than 4-year follow-up. AB - STUDY DESIGN: Retrospective case series of five consecutive patients. OBJECTIVE: To determine the oncological outcomes and morbidity rates after en bloc excisions of cervical chordomas. SUMMARY OF BACKGROUND DATA: Studies have demonstrated that en bloc surgical excision of chordoma with negative margins results in improved local disease control and survival compared with intralesional resections. Chordomas arising from the cervical spine are rare and they present unique challenges for en bloc tumor excision. We present a series of five consecutive cases of cervical chordoma managed with en bloc tumor excision, which represents one of the largest surgical experiences of cervical chordomas reported to date. METHODS: A retrospective review of our institutional spine tumor database identified five consecutive patients who underwent en bloc tumor excision for cervical spine chordoma from 2000 to 2007. We analyze their surgical margins, perioperative complications, tumor recurrence rate, and survival. RESULTS: Our review demonstrated that dysphagia and cervicalgia were the most common presenting symptoms for cervical chordoma. The mean age of diagnosis in this cohort was 52.4 years and our mean follow-up is 54.7 months. All five patients required multistage procedures to achieve en bloc tumor excision. Independent analysis of the surgical margins by the pathologists revealed that marginal en bloc excisions were achieved in all five patients. Our 30-day perioperative complication was significant for one case of transient radiculopathy with paresis and one wound infection. Other long-term complications included three cases with pseudoarthrosis with instrumentation failures requiring surgical revisions. There were no neurological or cerebrovascular complications. The mean disease-free survival after en bloc spondylectomy for cervical chordoma was 84.2 months in this cohort. CONCLUSION: En bloc excision of chordoma, whether wide or marginal, is the most ideal for treatment to prolong disease-free survival. En bloc excisions of chordomas in the cervical spine are technically complex procedures but can be performed with acceptable safety and perioperative morbidity. PMID- 22048654 TI - The pattern of lymph node metastasis and the suitability of 7th UICC N stage in predicting prognosis of remnant gastric cancer. AB - BACKGROUNDS: The original disease and previous operation usually cause abnormal lymphatic drainage of remnant gastric cancer (RGC). We analyzed metastatic lymph nodes (MLNs) of RGCs to explore the pattern of lymphatic metastasis and rational surgical treatment for RGC. METHODS: Eighty-three RGC patients who underwent radical gastrectomy from July 1991 to July 2008 enrolled in this retrospective analysis. RESULTS: Original disease, tumor size, Borrmann type, depth of invasion, and histological type were related to an increased risk of lymph node (LN) metastasis (P < 0.05). Multivariate logistic analysis revealed that tumor size and depth of invasion were independent predictive factors of LN metastasis (P < 0.05). In comparison with upper one-third gastric cancer, patients with RGC tended to have a lower incidence of perigastric LN metastasis and higher incidence of metastasis to the mesojejunum and lower mediastinal LNs. A high incidence of MLNs in the No. 14 and mesojejunum was found from the patients who had previously undergone Billroth II reconstruction, while patients after Billroth I reconstruction had higher No. 12 and No. 13 LN metastasis rates. Cut point survival analysis demonstrated that the most appropriate cutoffs of MLNs were set at 0, 2, 6, and 9. Patients of 0, 1-2, 3-6, 7-9, or >=10 MLNs presented with median survival time of 37, 35, 24, 13, and 9 month, respectively. CONCLUSIONS: Preoperative diagnosis of depth of invasion and tumor size can help surgeons to evaluate LN metastasis. The 7th UICC N stage may be unsuitable and should be evaluated and improved in order to help surgeons rationally to estimate N stage of RGC. PMID- 22048655 TI - NS398 induces apoptosis in non-small cell lung cancer cells. AB - PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) can induce the apoptosis of many tumor cells and inhibit their growth. NS398 is an NSAID that inhibits COX 2 expression and induces tumor apoptosis via other pathways. The current study aims to observe the effects of NS398 on A549 cell apoptosis and investigate the apoptosis mechanism. METHODS: The A549 cells were treated with different NS398 concentrations. The growth inhibition of A549 cell was analyzed via a 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and morphologic alterations were observed to detect apoptosis. The expression of survivin and caspase-3 mRNA was quantified via reverse transcriptase polymerase chain reaction, and the expression of caspase-3 and p-AKT protein was detected via western blot analysis. RESULTS: The MTT results show that NS398 inhibits A549 cell growth. The inhibition rate of NS398 (400 MUmol/L) on A549 cells is up to 66.95% after 48 h of treatment. Simultaneously, the morphology experiment revealed significant apoptotic characteristics in A549 cells, such as green nuclear plasmid and different degrees of nuclear fragmentation. The expression of survivin mRNA was significantly reduced (P < 0.05, P < 0.01, and P < 0.001) and that of caspase-3 mRNA was significantly increased (P < 0.05 and P < 0.001) in the group treated with NS398 for 24 h in a dose-dependent manner. On the other hand, survivin and p-AKT were expressed at low levels (P < 0.01 and P < 0.001) and caspase-3 was increased significantly (P < 0.05 and P < 0.001) in the group treated with NS398 for 48 h in a dose-dependent manner. CONCLUSION: The current study proves that NS398 induces apoptosis in A549 cells, thereby inhibiting tumor growth. This function of NS398 may be related to the inhibition of AKT phosphorylation and survivin protein downregulation. PMID- 22048656 TI - Genome-wide association study of copy number variation identified gremlin1 as a candidate gene for lean body mass. AB - Lean body mass (LBM) is a heritable trait predicting a series of health problems, such as osteoporotic fracture and sarcopenia. We aim to identify sequence variants associated with LBM by a genome-wide association study (GWAS) of copy number variants (CNVs). We genotyped genome-wide CNVs of 1627 individuals of the Chinese population with Affymetrix SNP6.0 genotyping platform, which comprised of 9 40 000 copy number probes. We then performed a GWAS of CNVs with lean mass at seven sites: left and right arms, left and right legs, total of limb, trunk and whole body. We identified a CNV that is associated with LBM variation at the genome-wide significance level (CNV2073, Bonferroni corrected P-value 0.002 at right arm). CNV2073 locates at chromosome 15q13.3, which has been implicated as a candidate region for LBM by our previous linkage studies. The nearest gene, gremlin1, has a key role in the regulation of skeletal muscle formation and repair. Our results suggest that the gremlin1 gene is a potentially important gene for LBM variation. Our findings also show the utility and efficacy of CNV as genetic markers in association studies. PMID- 22048657 TI - A family-based association study of DIO2 and children mental retardation in the Qinba region of China. AB - Deiodinase enzyme II (DIO2) has an important role in individuals' thyroid hormones' level, the development of central and peripheral nervous systems and characterized by mental retardation (MR). The DIO2 gene was genotyped by using five haplotype-tagging single-nucleotide polymorphisms (SNPs) in 157 Chinese MR high-density family pedigrees, including 452 nuclear families and >1460 persons. The single marker and haplotype analyses were performed by Family-based Association Tests (FBAT). Three SNPs had P-values <0.05 in at least one inherited model survived with the correction. Several haplotypes composed of these SNPs were also associated with MR. The in silico analyses identified that one of the SNPs, rs1388378, may be a functional SNP. However, further in vitro studies of this SNP should be considered in elucidating its effect on gene expression and the possible role in MR susceptibility. PMID- 22048658 TI - A multiplex SNP assay for the dissection of human Y-chromosome haplogroup O representing the major paternal lineage in East and Southeast Asia. AB - The majority of human Y chromosomes in men from East and Southeast Asia, and a considerable proportion of Oceanian men, especially those from Remote Oceania, belong to haplogroup O, characterized by a 5-bp deletion known as M175 (rs2032678). Recent advances in Y-SNP (single-nucleotide polymorphism) discovery have substantially improved the phylogenetic resolution of haplogroup O sublineages. By taking advantage of this recent knowledge, we hereby introduce a sensitive Y-SNP multiplex genotyping assay for the dissection of haplogroup O into its most significant sublineages. The multiplex assay thus provides an efficient way to infer patrilineal biogeographic ancestry in males of Asian/Oceanian patrilineal descent, and is suitable for applications in human population genetics, anthropological, genealogical, as well as forensic studies. PMID- 22048659 TI - Extending unsupported metal-only Lewis pairs to palladium. AB - Synthesis of the first unsupported palladium-to-main group metal Lewis pair is reported, including a new synthesis for heteroleptic mono(NHC)-monophosphine palladium(0) complexes. All compounds were analysed by single crystal X-ray diffraction, multinuclear NMR spectroscopy and density functional theory calculations. PMID- 22048660 TI - Comparative genomics: mammalian alignments reveal human functional elements. PMID- 22048661 TI - Epigenetics: inheriting a long life. PMID- 22048662 TI - Software for systems biology: from tools to integrated platforms. AB - Understanding complex biological systems requires extensive support from software tools. Such tools are needed at each step of a systems biology computational workflow, which typically consists of data handling, network inference, deep curation, dynamical simulation and model analysis. In addition, there are now efforts to develop integrated software platforms, so that tools that are used at different stages of the workflow and by different researchers can easily be used together. This Review describes the types of software tools that are required at different stages of systems biology research and the current options that are available for systems biology researchers. We also discuss the challenges and prospects for modelling the effects of genetic changes on physiology and the concept of an integrated platform. PMID- 22048663 TI - Regulatory RNA: layer by layer. PMID- 22048665 TI - The HEART study: a real-world experience using the CID Chrono Carbostent in primary and rescue PCI. AB - BACKGROUND: Chrono Carbostent (CID, Saluggia, Italy) is characterized by a peculiar coating with Carbofilm which could reduce the risk of thrombosis as compared to other bare metal stents (BMS). This feature should be particularly useful in the setting of primary or rescue percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We tested the efficacy and safety of this stent in patients with STEMI undergoing primary or rescue PCI. Inclusion criteria included the diagnosis of STEMI, a coronary anatomy suitable for stenting and no contraindications to dual antiplatelet therapy for at least 1 month. The primary endpoint was the composite of the following major adverse cardiac events (MACEs) at 12 months: death, recurrence of myocardial infarction and target vessel revascularization. RESULTS: One hundred and seven STEMI patients treated with Chrono Carbostent implantation were enrolled. Eighty-three (77%) patients underwent primary and 24 (23%) rescue PCI. A total of 148 stents were successfully implanted. Cardiogenic shock was present in 12 (11%) patients and in-hospital mortality was 6.5%. Cumulatively, the rate of MACEs at 12 months was 17.7% (deaths 7.4%, target lesion revascularization 9.3%). CONCLUSIONS: In unselected patients with STEMI treated by urgent PCI, the Chrono Carbostent showed a low rate of events in those patients surviving the acute phase of myocardial infarction. Unfortunately, and especially for patients in cardiogenic shock, survival continued to be relatively independent of interventional treatment, even when successfully completed, thus strictly linking prognosis of STEMI to severity of clinical presentation. PMID- 22048664 TI - Controlling gene expression in response to stress. AB - Acute stress puts cells at risk, and rapid adaptation is crucial for maximizing cell survival. Cellular adaptation mechanisms include modification of certain aspects of cell physiology, such as the induction of efficient changes in the gene expression programmes by intracellular signalling networks. Recent studies using genome-wide approaches as well as single-cell transcription measurements, in combination with classical genetics, have shown that rapid and specific activation of gene expression can be accomplished by several different strategies. This article discusses how organisms can achieve generic and specific responses to different stresses by regulating gene expression at multiple stages of mRNA biogenesis from chromatin structure to transcription, mRNA stability and translation. PMID- 22048667 TI - Nanoconfinement effects in energy storage materials. AB - Nanoconfinement effects have been studied to understand and to modify thermodynamic and kinetic properties of energy storage materials and to improve their cyclic behaviour. The paper addresses various aspects in the research and development of hydrogen storage materials and batteries. Fundamental relationships and the state-of-the art in the prediction of properties and experimental observations will be outlined and structure-property-relationships will be discussed for some hydrogen storage materials. Similar nanoconfinement effects in lithium battery anode materials will be addressed. PMID- 22048666 TI - Diffusion tensor imaging of the median nerve: intra-, inter-reader agreement, and agreement between two software packages. AB - OBJECTIVE: To assess intra-, inter-reader agreement, and the agreement between two software packages for magnetic resonance diffusion tensor imaging (DTI) measurements of the median nerve. MATERIALS AND METHODS: Fifteen healthy volunteers (seven men, eight women; mean age, 31.2 years) underwent DTI of both wrists at 1.5 T. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the median nerve were measured by three readers using two commonly used software packages. Measurements were repeated by two readers after 6 weeks. Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used for statistical analysis. RESULTS: ICCs for intra-reader agreement ranged from 0.87 to 0.99, for inter-reader agreement from 0.62 to 0.83, and between the two software packages from 0.63 to 0.82. Bland-Altman analysis showed no differences for intra- and inter-reader agreement and agreement between software packages. CONCLUSION: The intra-, inter-reader, and agreement between software packages for DTI measurements of the median nerve were moderate to substantial suggesting that user- and software-dependent factors contribute little to variance in DTI measurements. PMID- 22048668 TI - Biomedical applications of photoacoustic imaging with exogenous contrast agents. AB - Photoacoustic imaging is a biomedical imaging modality that provides functional information, and, with the help of exogenous contrast agents, cellular and molecular signatures of tissue. In this article, we review the biomedical applications of photoacoustic imaging assisted with exogenous contrast agents. Dyes, noble metal nanoparticles, and other constructs are contrast agents which absorb strongly in the near-infrared band of the optical spectrum and generate strong photoacoustic response. These contrast agents, which can be specifically targeted to molecules or cells, have been coupled with photoacoustic imaging for preclinical and clinical applications ranging from detection of cancer cells, sentinel lymph nodes, and micrometastasis to angiogenesis to characterization of atherosclerotic plaques. Multi-functional agents have also been developed, which can carry drugs or simultaneously provide contrast in multiple imaging modalities. Furthermore, contrast agents were used to guide and monitor the therapeutic procedures. Overall, photoacoustic imaging shows significant promise in its ability to assist in diagnosis, therapy planning, and monitoring of treatment outcome for cancer, cardiovascular disease, and other pathologies. PMID- 22048669 TI - Seasonal variation and health risk assessment of polycyclic aromatic hydrocarbons in Miaoli city, Taiwan. AB - The ambient PAHs levels in the downtown area of a traditional small city were analyzed for winter and summer seasons. A total of 16 PAHs in gaseous and particulate phase were quantified. The average gaseous PAHs were 2,189 +/- 1,194 and 623.8 +/- 545.1 ng/m(3) in winter and summer seasons, respectively. For the PAHs in particulate phase, they were 40.32 +/- 12.15 and 11.99 +/- 5.63 ng/m(3) in winter and summer seasons, respectively. These values were comparable to those reported for large cities or even higher. The estimated BaPeq was 12.32 +/- 6.34 ng/m(3). As low-molecular-weight PAHs primarily existed in gaseous phase, high molecular-weight PAHs in particulate phase became a significant fraction of total particulate phase PAHs. Particulate phase PAHs was significantly inversely associated with the ambient temperature for each individual PAHs species. However, this relationship did not exist for high-molecular-weight PAHs in gaseous phase. The results indicated the photo-degradation of high-molecular weight PAHs should warrant a further thoughtfully investigation. PMID- 22048671 TI - The rise and fall of England's National Programme for IT. PMID- 22048673 TI - Technology for development: innovation is not enough. PMID- 22048674 TI - Physiotherapy trials for the 21st century: time to raise the bar? PMID- 22048675 TI - Reducing global health inequalities. part 3: collaboration and funding. PMID- 22048676 TI - Origins of Western diseases. AB - Recent gynaecological studies show that childbirth, constipation, trauma and surgery cause injuries to autonomic nerves at different anatomical sites in the female pelvis resulting in endometriosis, adenomyosis and fibroids. Re-growth of abnormal nerves causes allodynic symptoms ('light touch causing pain or discomfort') some years later including vulvodynia, dyspareunia, dysmenorrhea, irritative bladder and bowel symptoms. Further consequences of autonomic denervation include tissue hypoplasia and hyperplasia, visceral dysfunction, susceptibility to infection, alcohol, tobacco and drugs, as well as pain with sensitization of the central nervous system. The 'autonomic denervation' view extrapolates these observations from the female pelvis to the varied anatomy of branches of the cardiac and coeliac plexi to provide primary mechanisms for many forms of Western disease. This account sets out the autonomic denervation view, identifies features of autonomic denervation in extrapelvic organs, and, contrasts it with prior accounts of chronic Western diseases including those of DP Burkitt, PRJ Burch and DP Barker. PMID- 22048677 TI - The 'gender gap' in authorship in nursing literature. AB - OBJECTIVES: Gender bias has been found in medical literature, with more men than women as first or senior authors of papers, despite about half of doctors being women. Nursing is about 90% female, so we aimed to determine if similar biases exist in nursing literature. DESIGN: Taking the eight non-specialist nursing journals with the highest impact factors for that profession, we counted the numbers of men and women first authors over 30 years. SETTING: We used nursing journals from around the world which attract the highest impact factors for nursing publication. PARTICIPANTS: Eight journals qualified for entry, three from the United Kingdom, four from the United States of America, and one from Australia. MAIN OUTCOME MEASURES Using Chi-square and Fisher exact tests, we determined differences between the numbers of men and women across all the journals, between countries (USA, UK and Australia), changes over the 30 years, and changes within journals over time. RESULTS Despite the small proportion of men in the nursing workforce, up to 30% of first authors were men. UK journals were more likely to have male authors than USA journals, and this increased over time. USA journals had proportions of male first authors consistent with the male proportion of its nursing workforce. CONCLUSIONS In the UK (though not in the USA) gender bias in nursing publishing exists, even though the nursing workforce is strongly feminized. This warrants further research, but is likely to be due to the same reasons for the gender gap in medical publishing; that is, female nurses take time out to have families, and social and family responsibilities prevent them taking opportunities for career progression, whereas men's careers often are not affected in such ways. PMID- 22048678 TI - The introduction of numerical methods to assess the effects of medical interventions during the 18th century: a brief history. PMID- 22048679 TI - Schizophrenia as segmental progeria. AB - Schizophrenia is associated with a variety of physical manifestations (i.e. metabolic, neurological) and despite psychotropic medication being blamed for some of these (in particular obesity and diabetes), there is evidence that schizophrenia itself confers an increased risk of physical disease and early death. The observation that schizophrenia and progeroid syndromes share common clinical features and molecular profiles gives rise to the hypothesis that schizophrenia could be conceptualized as a whole body disorder, namely a segmental progeria. Mammalian cells employ the mechanisms of cellular senescence and apoptosis (programmed cell death) as a means to control inevitable DNA damage and cancer. Exacerbation of those processes is associated with accelerated ageing and schizophrenia and this warrants further investigation into possible underlying biological mechanisms, such as epigenetic control of the genome. PMID- 22048681 TI - Effects of myocardial fibrosis and ventricular dyssynchrony on response to therapy in new-presentation idiopathic dilated cardiomyopathy: insights from cardiovascular magnetic resonance and echocardiography. AB - AIMS: To determine whether the extent of myocardial fibrosis by late-gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR), and echocardiographic ventricular dyssynchrony are independently associated with response to medical therapy in patients with newly diagnosed idiopathic dilated cardiomyopathy (DCM). Myocardial fibrosis and ventricular dyssynchrony are frequent findings in DCM. Previous studies focused on patients with established cardiomyopathy; however, the degree of myocardial fibrosis and ventricular dyssynchrony at presentation and their role in perpetuating left ventricular (LV) dysfunction in DCM remains unclear. Those studies of individuals with long-standing DCM did not characterize patients early in the disease course, and may not have included those with significant improvement in LV function. Thus factors contributing to LV recovery are uncertain. METHODS AND RESULTS: Consecutive patients with a new diagnosis of DCM [LV ejection fraction (EF) <=45%] made within the preceding 2 weeks were recruited. Patients underwent LGE-CMR, echocardiography, 6-minute walk testing, cardiopulmonary exercise testing, and blood sampling for measurement of serum amino-terminal pro-brain natiuretic peptide (NT-pro-BNP) concentration at baseline. Baseline patient characteristics were compared with a cohort of healthy volunteers. Myocardial fibrosis by LGE-CMR was quantified, identified by experienced observers blinded to patient outcome. Left ventricular systolic function was reassessed after 5 months of optimal medical therapy. Sixty-eight patients with DCM and 19 healthy volunteers were studied. DCM patients were studied a median 12.5 days following diagnosis. Compared with healthy controls, DCM patients exhibited greater inter- and intra-ventricular dyssynchrony. Twenty four per cent of DCM patients exhibited LGE at diagnosis. Among DCM patients with LGE, the mean fibrosis mass was 2.2 +/- 1.3 g. On multivariate analysis, strain dyssynchrony index, and fibrosis mass were independently associated with change in the LVEF over time (P<= 0.001). Late-gadolinium enhancement cardiovascular magnetic resonance conferred additive value for modelling change in the LVEF beyond clinical and echocardiographic dyssynchrony parameters. CONCLUSION: The extent of myocardial fibrosis is independently associated with lack of response to medical therapy in new-presentation DCM, and LGE-CMR may thus be an important risk-stratifying investigation in these patients. Accurate risk stratification may permit more targeted pharmacological and device therapies for patients with newly diagnosed DCM. PMID- 22048683 TI - Dalton Transactions after 40 volumes. PMID- 22048682 TI - Contribution of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort. AB - AIMS: The contemporary impact of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic on heart disease in South Africa (>5 million people affected) is unknown. The Heart of Soweto Study provides a unique opportunity to identify the contribution of cardiac manifestations of this epidemic to de novo presentations of heart disease in an urban African community in epidemiological transition. METHODS AND RESULTS: Chris Hani Baragwanath Hospital services the >1 million people living in Soweto, South Africa. A prospective, clinical registry captured data from all de novo cases of heart disease presenting to the Cardiology Unit during 2006-08. We describe all cases where HIV/AIDS was concurrently diagnosed. Overall, 518 of 5328 de novo cases of heart disease were identified as HIV-positive (9.7%) with 54% of these prescribed highly active anti-retroviral therapies on presentation. Women (62%) and Africans (97%) predominated with women being significantly younger than men 38 +/- 13 vs. 42 +/- 13 years (P = 0.002). The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (196 cases, 38%); being prescribed more anti-retroviral therapy (127/196 vs. 147/322; odds ratio 2.85, 95% confidence interval 1.81-3.88) with higher viral loads [median 110 000 (inter-quartile range 26 000-510 000) vs. 19 000 (3200-87 000); P = 0.018] and a lower CD4 count [median 180 (71-315) vs. 211 (96-391); P = 0.019] than the rest. An additional 128 cases (25%) were diagnosed with pericarditis/pericardial effusion with a range of other concurrent diagnoses evident, including 42 cases (8.1%) of HIV related pulmonary arterial hypertension. Only 14 of all 581 cases of coronary artery disease (CAD) (2.4%, mean age 41 +/- 13 years) were confirmed HIV positive. CONCLUSION: Cardiac manifestations of HIV/AIDS identified within this cohort were relatively infrequent. While HIV-related cardiomyopathy and pericardial disease remain important targets for early detection and treatment in this setting, HIV-related cases of CAD remain at historically low levels. PMID- 22048684 TI - Charge transport in single molecular junctions at the solid/liquid interface. AB - Charge transport characteristics in metal-metal nanocontacts and single molecular junctions were studied at electrified solid-liquid interfaces employing a scanning tunneling microscope-based break junction technique, in combination with macroscopic electrochemical methods, in non-conducting solvents and in an electrochemical environment. We aim to demonstrate recent attempts in developing fundamental relationships between molecular structure, charge transport characteristics, and nanoscale electrochemical concepts. After an introduction and brief description of the experimental methodology, a case study on the electrical and mechanical properties of gold atomic contacts in aqueous electrolytes is presented. In experiments with alkanedithiol and alpha,omega biphenyldithiol molecular junctions the role of sulfur-gold couplings and molecular conformation, such as gauche defects in alkyl chains and the torsion angle between two phenyl rings, are addressed. The combination with quantum chemistry calculations enabled a detailed molecular-level understanding of the electronic structure and transport characteristics of both systems. Employing the concept of "electrolyte gating" to 4,4'-bipyridine and redox-active molecules, such as perylene bisimide derivatives, the construction of "active" symmetric and asymmetric molecular junctions with transistor- and diode-like behavior upon polarization in an electrochemical environment will be demonstrated. The latter experimental data could be represented quantitatively by the Kutznetsov/Ulstrup model, assuming a two-step electron transfer with partial vibration relaxation. Finally, we show that (individual) surface-immobilized gold clusters within the quantum-confined size range exhibit features of locally addressable multistate electronic switching upon electrolyte gating, which appears to be reminiscent of a sequential charging through several redox states. The examples addressed here demonstrate the uniqueness and capabilities of an electrochemical approach for the fundamental understanding and for potential applications in nano- and molecular electronics. PMID- 22048685 TI - Progress and future of pyrethroids. AB - After the chemical structure of "natural pyrethrins," the insecticidal ingredient of pyrethrum flowers, was elucidated, useful synthetic pyrethroids provided with various characteristics have been developed by organic chemists throughout the world, leading to the advancement of pyrethroid chemistry. Even in pyrethroids with high selective toxicity, a chemical design placing too much importance on efficacy improvements may invite loss of the safety margin. It is strongly hoped that the development of household pyrethroids and their preparations for use in living environments around humans and pets will be achieved in the future by retaining the characteristics of natural pyrethrins. PMID- 22048686 TI - Star-shaped mesogens -- hekates: the most basic star structure with three branches. AB - The chapter introduces and defines the term star-shaped mesogens as a highly symmetric subgroup of multipodes. Hekates, the three arm stars, are in the focus of the other sections. Flexible, semi-flexible and shape-persistent mesogens can be distinguished. The chapter presents various modes of self-assembly which account for nanosegregation and space-filling. Recent examples are semi-flexible structures which fold to E-shaped conformers followed by self-organisation in columnar 2D and 3D and micellar cubic structures. Hekates are mesogens that will allow the design of complex mesomorphic and functional materials in the future. PMID- 22048687 TI - Reversibly expanded encapsulation complexes. AB - Synthetic receptors that surround their target molecules - self assembled capsules and deep cavitands - have emerged as the most realistic models of enzymes active sites. They were introduced to study the behaviour of molecules isolated in small spaces and it has become increasingly clear that the behavior of molecules in dilute aqueous solution does not reflect their behavior in confimed spaces. The synthetic receptors fold around their target guests, isolate them from the bulk solvent, provide a hydrophobic environment and present the guests with each other in a limited space. These features combine to show high binding selectivity, large rate from the ground up; they are designed, synthesized then tested. In recent years, we have found a short-cut to total synthesis; some capsules readily insert spacer elements in the presence of suitable guests that fill the enlarged spaces. This expands the repertoire of containers and the present review describes their structures, the nature of the spaces inside, the exchange dynamics, and the rules that govern their formation. PMID- 22048688 TI - Bismuth-catalyzed addition of silyl nucleophiles to carbonyl compounds and imines. AB - Bismuth triflate was found to be an efficient catalyst both in the Mannich-type reaction of silyl enolates and in the Sakurai reaction of allyltrimethylsilane with N-alkoxycarbonylamino sulfones. The reactions proceeded smoothly with a low catalyst loading of Bi(OTf)(3).4H(2)O (0.5-5.0 mol%) to afford the corresponding protected beta-amino carbonyl compounds and homoallylic amines in very good yields (up to 96%). The latter compounds could also be obtained via a bismuth mediated three-component reaction. We have also developed an efficient vinylogous Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan with various aromatic aldehydes mediated by bismuth triflate in a low catalyst loading (1 mol%). The reaction proceeds rapidly and affords the corresponding 5 [hydroxy(aryl)methyl]furan-2(5H)-ones in high yields with good to very good diastereoselectivities (diastereoisomeric ratios>98:2). Such selectivities, although previously reported with other Lewis acids, could be achieved with a much lower catalyst loading. 5-[Hydroxy(alkyl)methyl]furan-2(5H)-ones derived from ketones could also be obtained with good diastereoselectivities. The vinylogous Mukaiyama aldol reaction has also been extended to 2,2-dimethyl-6 methylene-4-(trimethyl-silyloxy)-1,3-diox-4-ene using 1 mol% of Bi(OTf)(3).4H(2)O. PMID- 22048689 TI - Spectral analysis of systemic and cerebral cardiovascular variabilities in preterm infants: relationship with clinical risk index for babies (CRIB). AB - Frequency spectrum analysis of circulatory signals has been proposed as a potential method for clinical risk assessment of preterm infants by previous studies. In this study, we examined the relationships between various spectral measures derived from systemic and cerebral cardiovascular variabilities and the clinical risk index for babies (CRIB II). Physiological data collected from 17 early low birth weight infants within 1-3 h after birth were analysed. Spectral and cross-spectral analyses were performed on heart rate variability, blood pressure variability and cerebral near-infrared spectroscopy measures such as oxygenated and deoxygenated haemoglobins (HbO(2) and HHb) and tissue oxygenation index (TOI). In addition, indices related to cardiac baroreflex sensitivity and cerebral autoregulation were derived from the very low, low- and mid-frequency ranges (VLF, LF and MF). Moderate correlations with CRIB II were identified from mean arterial pressure (MAP) normalized MF power (r = 0.61, P = 0.009), LF MAP HHb coherence (r = 0.64, P = 0.006), TOI VLF percentage power (r = 0.55, P = 0.023) and LF baroreflex gain (r = -0.61, P = 0.01 after logarithmic transformation), with the latter two parameters also highly correlated with gestational age (r = -0.75, P = 0.0005 and r = 0.70, P = 0.002, respectively). The relationships between CRIB II and various spectral measures of arterial baroreflex and cerebral autoregulation functions have provided further justification for these measures as possible markers of clinical risks and predictors of adverse outcome in preterm infants. PMID- 22048691 TI - The improvement of an anti-CD22 immunotoxin: conversion to single-chain and disulfide stabilized form and affinity maturation by alanine scan. AB - HA22-LR is a recombinant immunotoxin for the treatment of B-cell malignancies that contains the Fv portion of an anti-CD22 antibody fused to a functional portion of Pseudomonas exotoxin A. In the present study, we attempted to improve this molecule. First, we produced a single-chain version of HA22-LR (scdsFv-HA22 LR) in which a peptide linker was introduced between the disulfide-linked light and heavy chains to enable production via single fermentation. No difference in cytotoxic activity was observed between scdsFv-HA22-LR and prototype HA22-LR. Next, we attempted to increase the affinity of scdsFv-HA22-LR by using alanine scanning mutagenesis of complementarity determining regions (CDRs) to assess the specific contribution of each CDR residue to the antigen binding. We found that mutation of asparagine 34 in VLCDR1, which is located at the VL/VH interface, to alanine (N34A) caused a substantial increase in affinity and activity. Estimated KD values measured by fluorescence-activated cell sorting were lowered by 10 fold: 0.056 nM in the N34A mutant compared to 0.58 nM in wild type (WT). Cell viability assays of CD22-positive B-cell lymphoma and leukemia cell lines showed that the N34A mutant had increased cytotoxicity ranging from ~2 (HAL-1, IC 50(WT): 2.37 +/- 0.62 ng/ml, IC 50(N34A): 1.32 +/- 0.41 ng/ml) to 10 (SUDHL-6, IC 50(WT): 0.47 +/- 0.090 ng/ml, IC 50(N34A): 0.048 +/- 0.018 ng/ml)-fold compared to WT immunotoxin. The present study suggests that the N34A mutant of scdsFv-HA22 LR could have important consequences in a clinical setting. PMID- 22048692 TI - Recent advances using FcRn overexpression in transgenic animals to overcome impediments of standard antibody technologies to improve the generation of specific antibodies. AB - This review illustrates the salutary effects of neonatal Fc receptor (FcRn) overexpression in significantly improving humoral immune responses in the generation of antibodies for immunotherapy and diagnostics. These include: (1) improved IgG protection; (2) augmented antigen-specific humoral immune response with larger numbers of antigen specific B cells, thus offering a wider spectrum of clones; (3) generation of antibodies against weakly immunogenic antigens; (4) significant improvements in the number and substantial developments in the diversity of hybridomas. FcRn transgenesis thus confers a number of practical benefits, including faster antibody production, higher antibody yields and improved generation of hybridomas for monoclonal antibody production. Notably, these efficiencies in polyclonal antibody production were also demonstrated in FcRn transgenic rabbits. Overall, FcRn transgenic animals yield more antibodies and provide a route to the generation of antibodies against antigens of low immunogenicity that are difficult to obtain using currently available methods. PMID- 22048693 TI - Neonatal Fc receptor and IgG-based therapeutics. AB - The majority of potent new biologics today are IgG-based molecules that have demonstrated tissue-targeting specificity with favorable clinical response. Several factors determine the efficacy of these products, including target specificity, serum half-life and effector functions via complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity or drug conjugates. In this review, we will focus on the interaction between therapeutic antibody and neonatal Fc receptor (FcRn), which is one of the critical factors in determining the circulating antibody half-life. Specifically, we will review the fundamental biology of FcRn, FcRn functions in various organs, Fc mutations designed to modulate binding to FcRn, IgG-based therapeutics that directly exploit FcRn functions and tools and strategies used to study FcRn-IgG interactions. Comprehensive understanding of FcRn-IgG interactions not only allows for development of effective therapeutics, but also avoidance of potential adverse effects. PMID- 22048694 TI - Biochemical and biophysical characterization of humanized IgG1 produced in Pichia pastoris. AB - The first full length IgG produced in Pichia pastoris was reported in late 1980. However, use of a wild-type Pichia expression system to produce IgGs with human like N-linked glycans was not possible until recently. Advances in glycoengineering have enabled organisms such as Pichia to mimic human N-glycan biosynthesis and produce IgGs with human glycans on an industrial scale. Since there are only a few reports of the analytical characterization of Pichia produced IgG, we summarize the results known in this field, and provide additional characterization data generated in our laboratories. The data suggest that Pichia-produced IgG has the same stability as that produced in Chinese hamster ovary (CHO) cells. It has similar aggregation profiles, charge variant distribution and oxidation levels as those for a CHO IgG. It contains human N linked glycans and O-linked single mannose. Because of the comparable biophysical and biochemical characteristics, glycoengineered Pichia pastoris is an attractive expression system for therapeutic IgG productions. PMID- 22048696 TI - Heart rate as an independent risk factor in patients with multiple organ dysfunction: a prospective, observational study. AB - PURPOSE: To study the association between baseline heart rate and outcome in patients with multiple organ dysfunction (MODS) as well as the course of heart rate over the first 4 days during MODS. METHODS: Prospective observational study in 89 patients with MODS, defined as an APACHE-II score >=20. Baseline heart rate (HR(0)) was determined over a 60-minute period at the time of MODS diagnosis. 28 day all-cause mortality was the primary endpoint of the study, a fall of the APACHE-II score by 4 points or more from day 0 to day 4 constituted the secondary endpoint. Hazard ratios for heart rate of 90 beats per minute (bpm) or greater relative to less than 90 bpm were calculated using Cox proportional hazards model and adjusted for confounding variables. RESULTS: Median baseline heart rate was 83 bpm in survivors and 92 bpm in non-survivors (p = 0.048). 28-day mortality was 32 and 61% in patients with HR(0) < 90 bpm and HR(0) >= 90 bpm, respectively. The adjusted hazard ratio for 28-day mortality was 2.30 (95% confidence interval 1.21 4.36, p = 0.001) for HR(0) >= 90 bpm relative to HR(0) < 90 bpm. No correlation was found between baseline heart rate and the secondary endpoint. From day 0 to day 4, heart rate remained elevated in all patients, as well as in survivors and non-survivors. CONCLUSIONS: A heart rate >=90 bpm at the time of MODS diagnosis is an independent risk factor for increased 28-day mortality. As in patients with cardiovascular conditions such as coronary heart disease or chronic heart failure, heart rate might constitute a target for heart rate-lowering therapy in the narrow initial treatment window of MODS. PMID- 22048697 TI - Influence of algorithm-based analgesia and sedation in patients after sudden cardiac arrest. AB - PURPOSE: The aim of this study was to analyse the effect of an algorithm-based analgesic-sedative management on mechanical ventilation time and length of stay in a cardiological ICU with critical ill patients after sudden cardiac arrest. METHODS: We examined 100 patients after successful resuscitation in a retrospective-prospective single-centre trial by introducing an algorithm-based sedation management. Demographic data, severity of illness classified by APACHE II score (Acute Physiology and Chronic Health Evaluation II), neurological outcome and data for mechanical ventilation time and length of stay were acquired for both groups. RESULTS: We found a shorter ventilation time for young patients without severe illness, whereby significant longer ventilation time was observed for patients with higher APACHE II score. Between both groups, we found no significant differences in mechanical ventilation time and length of stay. CONCLUSIONS: Our results demonstrate a tendency towards a reduction of mechanical ventilation time for patients without severe illness after sudden cardiac arrest achieved by implementation of a new sedation management, whereby significant longer ventilation time was observed for severe ill patients. Because of lack of statistical significance of our present study, a randomized study with sufficient power is necessary to demonstrate positive effects of a standardized sedation management and its influence on severity of illness. PMID- 22048698 TI - Polar compounds isolated from the leaves of Albertisia delagoensis (Menispermaceae). AB - Aqueous infusions of the leaves of the shrub Albertisia delagoensis (Menispermaceae) are used in South Africa in traditional Zulu medicine to alleviate a variety of symptoms, including fever, and intestinal problems. We report the analysis of such an aqueous extract using the HPLC-NMR technique. A number of polar compounds were identified, including proto-quercitol, nicotinic acid, allantoic acid, 3,4-dihydroxy-benzoic acid, phthalic acid and the aporphine alkaloid derivative roemrefidine. Allantoic acid and roemrefidine have been fully characterised by (1)H- and (13)C-NMR and mass spectrometry. Earlier reports of antiplasmodial activity of roemrefidine and of A. delagoensis extracts are correlated with this study and with the antipyretic properties of neutral aqueous extracts. PMID- 22048699 TI - Small molecule library synthesis using segmented flow. AB - Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this paper we describe a method that adapts flow chemistry to the synthesis of libraries of compounds using a fluorous immiscible solvent as a spacer between reactions. The methodology was validated in the synthesis of two small heterocycle containing libraries. The reactions were performed on a 0.2 mmol scale, enabling tens of milligrams of material to be generated in a single 200 mL reaction plug. The methodology allowed library synthesis in half the time of conventional microwave synthesis while maintaining similar yields. The ability to perform multiple, potentially unrelated reactions in a single run is ideal for making small quantities of many different compounds quickly and efficiently. PMID- 22048700 TI - Design, synthesis and biological evaluation of hydroxamic acid derivatives as potential high density lipoprotein (HDL) receptor CLA-1 up-regulating agents. AB - Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) were reported in our recent publication as novel human high density lipoprotein (HDL) receptor CD36 and Lysosomal integral membrane protein-II Analogous-1 (CLA-1) up regulators. As part of a broader effort to more fully explore the structure activity relationships (SAR) of CLA-1 up-regulators, we synthesized a series of hydroxamic acid derivatives and evaluated their CLA-1 up-regulating activities in HepG2 cells. Some compounds exhibited over 10-fold up-regulation of CLA-1 expression in HepG2 cells at 10 MUg/mL concentration. The compound 1g showed the best potency, with a lower EC(50) than TSA (EC(50) = 0.32 MUM versus 1.2 MUM). These compounds provide early new CLA-1 up-regulators with potential for treating atherosclerosis. PMID- 22048702 TI - Joint space narrowing, cartilage and physical function: are we deceived by measurements and distributions? PMID- 22048701 TI - Effect of Ginkgo biloba extract 50 on immunity and antioxidant enzyme activities in ischemia reperfusion rats. AB - The aim of the study was to investigate the effect of Ginkgo biloba extract 50 (GBE50), a well-known natural antioxidant, against immunity and antioxidant enzyme activities in ischemia reperfusion (IR) rats. Rats were then divided into six groups fed for 15 days with the same diet: three groups (IV, V, VI) were treated by different doses of GBE50 suspension [20, 40, or 60 mg/kg body weight by oral gavage every day at a fixed time (10.00 a.m.)] (equal to 5, 10 and 20 times, respectively, the maximum recommended human dose), and three groups (I, II, III) were untreated. At the end of the experiment, rats' hearts were subjected to 30 min of ischemia followed by 90 min of reperfusion. Results showed that IR significantly enhanced heart rate, S-T height, myocardium (myeloperoxidase) MPO activity and blood interleukin-8 (IL-8), tumor necrosis factor Alpha (TNF-a), interleukin-1beta (IL-1beta) levels, blood aspartate transaminase (AST), lactate dehydrogenase (LDH), and creatinine kinase (CK) activities, reduced myocardium sodium-potassium adenosine triphosphatase (Na(+) K(+)-ATPase), calcium-magnesium adenosine triphosphatase (Ca(2+)-Mg(2+)-ATPase) activities and antioxidant enzyme activities in IR group (III) compared to sham control group (II). Pretreatment of GBE50 markedly significantly reduced heart rate, S-T height, myocardium MPO activity and blood IL-8, TNF-a, IL-1beta levels, blood AST, LDH, and CK activities, enhanced myocardium Na(+)-K(+)-ATPase, Ca(2+) Mg(2+)-ATPase activities and antioxidant enzyme activities in IR group (II) compared to IR group (III). The results suggested that the GBE50 may reduce the oxidative stress in the reperfused myocardium, and increased immunity and antioxidant activities in IR rats. PMID- 22048703 TI - Republished review: Triglycerides and atherogenic dyslipidaemia: extending treatment beyond statins in the high-risk cardiovascular patient. AB - Although statins significantly decrease the incidence of cardiovascular disease (CVD), residual CVD risk remains high. This may partly be due to uncorrected atherogenic dyslipidaemia. The driving force behind atherogenic dyslipidaemia is hypertriglyceridaemia, which results from hepatic oversecretion and/or hypocatabolism of triglyceride-rich lipoproteins, and is typical of type 2 diabetes and metabolic syndrome. Persistent atherogenic dyslipidaemia in patients treated with a statin according to low-density lipoprotein-cholesterol goals may be corrected with niacin, fibrates or n-3 fatty acids. Clinical trial evidence to inform best practice is limited, but new data support adding fenofibrate to a statin. A consistent feature of fibrate clinical trials is the specific benefit of these agents in dyslipidaemic patients and the improvement in diabetic retinopathy with fenofibrate. Ongoing clinical trials may provide good evidence for adding niacin to a statin. Low-dose n-3 fatty acids could be used routinely after a myocardial infarction, but the value of higher doses of n-3 fatty acids in reducing CVD risk remains to be demonstrated. PMID- 22048704 TI - Republished error management: Descriptions of verbal communication errors between staff. An analysis of 84 root cause analysis-reports from Danish hospitals. AB - INTRODUCTION: Poor teamwork and communication between healthcare staff are correlated to patient safety incidents. However, the organisational factors responsible for these issues are unexplored. Root cause analyses (RCA) use human factors thinking to analyse the systems behind severe patient safety incidents. The objective of this study is to review RCA reports (RCAR) for characteristics of verbal communication errors between hospital staff in an organisational perspective. METHOD: Two independent raters analysed 84 RCARs, conducted in six Danish hospitals between 2004 and 2006, for descriptions and characteristics of verbal communication errors such as handover errors and error during teamwork. RESULTS: Raters found description of verbal communication errors in 44 reports (52%). These included handover errors (35 (86%)), communication errors between different staff groups (19 (43%)), misunderstandings (13 (30%)), communication errors between junior and senior staff members (11 (25%)), hesitance in speaking up (10 (23%)) and communication errors during teamwork (8 (18%)). The kappa values were 0.44-0.78. Unproceduralized communication and information exchange via telephone, related to transfer between units and consults from other specialties, were particularly vulnerable processes. CONCLUSION: With the risk of bias in mind, it is concluded that more than half of the RCARs described erroneous verbal communication between staff members as root causes of or contributing factors of severe patient safety incidents. The RCARs rich descriptions of the incidents revealed the organisational factors and needs related to these errors. PMID- 22048705 TI - Isolated pericardial hydatid cyst. PMID- 22048707 TI - Ab initio study of chain branching reactions involving second generation products in hydrocarbon combustion mechanisms. AB - sec-Alkyl radicals are key reactive intermediates in the hydrocarbon combustion and atmospheric decomposition mechanisms that are formed by the abstraction of hydrogen from an alkane, or as a second generation product of n-alkyl H migrations, C-C bond scissions in branched alkyl radicals, or the bimolecular reaction between olefins and n-alkyl radicals. Since alkanes and branched alkanes, which the sec-alkyl radicals are derived from, make up roughly 40-50% of traditional fuels an understanding of their chemistry is essential to improving combustion systems. The present work investigates all H-migration reactions initiated from an sec-alkyl radical that involve the movement of a secondary hydrogen, for the 2-butyl through 4-octyl radicals, using the CBS-Q, G2, and G4 composite methods. The resulting thermodynamic and kinetic parameters are compared to similar reactions in n-alkyl radicals in order to determine underlying trends. Particular attention is paid to the effect of cis/trans and 1,3-diaxial interactions on activation energies and rate coefficients. When combined with our previous work on n-alkyl radical H-migrations, a complete picture of H-migrations in unbranched alkyl radicals is obtained. This full data set suggests that the directionality of the remaining branched chains has a minimal effect on the rate coefficients for all but the largest viable transition states, which is in stark contrast to the differences predicted by the structurally similar dimethylcycloalkanes. In fact the initial location of the secondary radical site has a greater effect on the rate than does the directionality of the remaining alkyl chains. The activation energies for secondary to secondary reactions are much closer to those of the secondary to primary H-migrations. However, the rate coefficients are found to be closer to the corresponding primary to primary reaction values. A significant ramification of these results is that there will be multiple viable reaction pathways for these reactions instead of only one dominant pathway as previously believed. PMID- 22048706 TI - Structure of the acyl-glucose-dependent anthocyanin 5-O-glucosyltransferase gene in carnations and its disruption by transposable elements in some varieties. AB - The pink, red and crimson petal colors of carnations (Dianthus caryophyllus) are produced by anthocyanins. The anthocyanins, pelargonidin and cyanidin can be modified by two glucoses at the 3 and 5 positions, and by a single malic acid. Petal color variation can result from failure of such modification, for example, the lack of a glucose at the 5 position is responsible for the color variants of some commercial varieties. With respect to this variation, modification by 5-O glucosyltransferase plays the most important role in glucosylation at the 5 position. Recently, we identified a novel acyl-glucose-dependent anthocyanin 5-O glucosyltransferase (AA5GT), that uses acyl-glucoses, but not UDP-glucose, as the glucose donor. Although we showed that loss of AA5GT expression was responsible for loss of glucosylation at the 5 position of anthocyanin in some varieties, the cause of this repression of AA5GT expression could not be determined. Here, we have succeeded in isolating the AA5GT gene and found that it consists of 12 exons and 11 introns. In carnation varieties lacking a glucose at the 5 position, we identified the insertion of two different retrotransposons, Ty1dic1 and Retdic1, into AA5GT. Ty1dic1, which belongs to the class I long terminal repeat (LTR) retrotransposons of Ty1/copia families, was inserted into exon 10. Retdic1, which includes a long interspersed nuclear element (LINE)-like sequence, was inserted into intron 5. Thus, insertion of either Ty1dic1 or Retdic1 can disrupt AA5GT and result in the lack of glucosylation at the 5 position in anthocyanins. PMID- 22048708 TI - A novel detection technique of hydrazine hydrate: modality change of hydrogen bonding-induced rapid and ultrasensitive colorimetric assay. AB - Ultrasensitive visual detection of hydrazine hydrate using a Au nanoparticles based colorimetric sensing system (ANCSS) is reported for the first time, which is based on the hydrogen bonding recognition and the modality change of hydrogen bonding from "linear" (simple hydrogen bond interactions) to "nonlinear" (a complicated hydrogen bond network) between as-modified Au nanoparticles (Au NPs). PMID- 22048709 TI - RNA: a new layer of regulation. PMID- 22048710 TI - Statistical evaluation of photon count rate data for nanoscale particle measurement in wastewaters. AB - The dynamic light scattering (DLS) technique can detect the concentration and size distribution of nanoscale particles in aqueous solutions by analyzing photon interactions. This study evaluated the applicability of using photon count rate data from DLS analyses for measuring levels of biogenic and manufactured nanoscale particles in wastewater. Statistical evaluations were performed using secondary wastewater effluent and a Malvern Zetasizer. Dynamic light scattering analyses were performed equally by two analysts over a period of two days using five dilutions and twelve replicates for each dilution. Linearity evaluation using the sixty sample analysis yielded a regression coefficient R(2) = 0.959. The accuracy analysis for various dilutions indicated a recovery of 100 +/- 6%. Precision analyses indicated low variance coefficients for the impact of analysts, days, and within sample error. The variation by analysts was apparent only in the most diluted sample (intermediate precision ~12%), where the photon count rate was close to the instrument detection limit. The variation for different days was apparent in the two most concentrated samples, which indicated that wastewater samples must be analyzed for nanoscale particle measurement within the same day of collection. Upon addition of 10 mg l(-1) of nanosilica to wastewater effluent samples, the measured photon count rates were within 5% of the estimated values. The results indicated that photon count rate data can effectively complement various techniques currently available to detect nanoscale particles in wastewaters. PMID- 22048711 TI - Magnetic resonance imaging: generating a new pulse in the physical therapy profession. AB - The ability to refer for diagnostic tests is particularly relevant to the topic of this special issue on magnetic resonance imaging (MRI). As a doctoring profession, one could argue that the ability to refer a patient for MRI (and other imaging applications) must be available to the direct-access physical therapist. Though the prescription for and use of MRI has not typically been considered within the scope of physical therapist practice, this may be the perfect time to challenge the obstacles precluding the obtainment of such diagnostic privileges and to specifically provide perspective on why and how such a specialized privilege could positively impact the provision of physical therapy services and patient outcomes. An expected obligation of such autonomy, however, is accountability. Is our entire profession adequately prepared to accept the role of, or the responsibilities associated with, referral for imaging privileges? PMID- 22048712 TI - The effect of 4 weeks of aerobic exercise on vascular and baroreflex function of young men with a family history of hypertension. AB - The effect of short-term aerobic exercise on vascular function of young individuals with a family history of hypertension was investigated. Thirty young men with a family history of hypertension were randomly assigned to either an exercise (n=15) or control (n=15) group. Exercise subjects performed 30 min of supervised cycle training at 65% of their maximal oxygen uptake (VO(2max)), three times per week for 4 weeks. Control subjects were asked to maintain their normal levels of physical activity. Peak leg and forearm blood flow were assessed using plethysmography and was determined as the highest blood flow following 5 min of reactive hyperemia. Cardiopulmonary baroreceptor (CPBR) sensitivity was measured using lower body negative pressure (LBNP) for 5 min at -20 mm Hg. CPBR was determined by calculating change of stroke volume and forearm vascular resistance at baseline and during LBNP. Carotid baroreceptor (CBR) sensitivity was assessed using neck suction at -20, -40, -60 and -80 mm Hg pressures, and was determined from RR interval divided by systolic blood pressure. Augmentation index (AIx), a measure of arterial stiffness, was assessed using applanation tonometry and was calculated as the ratio of augmented pressure and pulse pressure. The major findings were that the exercise group showed increase in leg vasodilation, reduction in AIx and increase in VO(2max) compared with the control group (P<0.05). However, there was no significant change for CPBR and CBR. A short-term moderate-intensity aerobic exercise intervention in young men with a family history of hypertension significantly reduced arterial stiffness and increased aerobic fitness. PMID- 22048713 TI - Impact of calibration on estimates of central blood pressures. AB - Using the Sphygmocor device it is recommended that the radial pressure wave is calibrated for brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP). However it has been suggested that brachial-to-radial pressure amplification causes underestimation of central blood pressures (BPs) using this calibration. In the present study we examined if different calibrations had an impact on estimates of central BPs and on the clinical interpretation of our results. On the basis of ambulatory BP measurements, patients were categorized into patients with controlled, uncontrolled or resistant hypertension. We first calibrated the radial pressure wave as recommended and afterwards recalibrated the same pressure wave using brachial DBP and calculated mean arterial pressure. Recalibration of the pressure wave generated significantly higher estimates of central SBP (P=0.0003 and P<0.0001 at baseline and P=0.0001 and P=0.0002 after 6 months). Using recommended calibration we found a significant change in central SBP in both treatment groups (P=0.05 and P=0.01), however, after recalibrating significance was lost in patients with resistant hypertension (P=0.15). We conclude that calibration with DBP and mean arterial pressure produces higher estimates of central BPs than recommended calibration. The present study also shows that this difference between the two calibration methods can produce more than a systematic error and has an impact on interpretation of clinical results. PMID- 22048714 TI - The effects of dietary patterns on plasma renin activity: results from the Dietary Approaches to Stop Hypertension trial. AB - A diet rich in fruits, vegetables and low-fat dairy products, and reduced in saturated fat, total fat and cholesterol (the 'DASH' diet) significantly lowers blood pressure (BP). Previous studies have documented that certain therapies that lower BP increase plasma renin activity (PRA). Using data from the Dietary Approaches to Stop Hypertension (DASH) trial, we assessed the effects of dietary patterns on PRA and determined the relationship of change in PRA with change in BP on each diet. After eating a control diet for 3 weeks, participants were then randomized to receive for 8 weeks: the control diet, a diet rich in fruits and vegetables (F/V), or the DASH diet. Baseline and follow-up levels of PRA were available in 381 participants. Compared with the control diet, the DASH diet increased PRA by 0.37 ng ml(-1) h(-1) (P=0.01). In multivariable linear regression analyses, there was an inverse association of PRA change with systolic BP change on the control diet (slope=-0.35, P=0.001), but PRA did not differ by BP change on the F/V diet (slope=-0.002, P=0.98) or DASH diet (slope=-0.08, P=0.32). These data suggest that a blunted counter-regulatory response of the renin-angiotensin system is associated with the BP-lowering effect of the F/V and DASH diets. PMID- 22048715 TI - A sex-specific effect of the CYP17A1 SNP rs11191548 on blood pressure in Chinese children. AB - CYP17A1 gene encodes the cytochrome P450 enzyme CYP17A1, a key enzyme involved in steroid metabolism. A single nucleotide polymorphism (SNP) near CYP17A1, rs11191548, showed significant association with hypertension in European adults. However, this association has not been demonstrated in children thus far. Additionally, the role of CYP17A1 in elevating blood pressure (BP) is unclear. We investigated the association of rs11191548 with hypertension in Chinese children. A total of 3422 children participated in the study, including 1009 children with elevated BP (EBP, including prehypertension and hypertension) and 2413 children with normal BP. SNP rs11191548 was associated with systolic BP (SBP) (CC vs TT: P=4.8 * 10(-4); additive model: P=0.002; dominant model: P=0.011; recessive model: P=0.001) and EBP (CC vs TT: odds ratio (OR)=0.43, 95% confidence interval (CI) 0.26-0.72, P=0.001; additive model: OR=0.74, 95% CI 0.61-0.90, P=0.002; dominant model: OR=0.76, 95% CI 0.60-0.96, P=0.022; recessive model: recessive model: OR=0.46, 95% CI 0.28-0.77, P=0.003) in girls, but there was no statistically significant association between the SNP and diastolic BP in boys or girls. Our results also showed that rs11191548 was more significantly associated with SBP and EBP in obese girls than in girls of normal weight. Our study indicated that the SNP rs11191548, near CYP17A1, was associated with EBP in children. Moreover, we found a sex-specific effect of rs11191548 on SBP in Chinese children. Further studies are necessary to clarify the association between this CYP17A1 polymorphism and BP. PMID- 22048716 TI - Ninth annual meeting of the Association for Cancer Immunotherapy (CIMT 2011), May 25-27, 2011, Mainz, Germany. PMID- 22048717 TI - A novel anti-Cyr61 antibody inhibits breast cancer growth and metastasis in vivo. AB - Cysteine-rich protein 61(CCN1/Cyr61) has been implicated as an important mediator in proliferation and metastasis of breast cancer, which indicated that blockage of Cyr61 might be a potent target for breast cancer treatment. However, the antitumor effect of anti-Cyr61 antibodies on breast cancer in vivo has not been reported so far. In this study, we reported the effect and likely mechanism of generated anti-human Cyr61 monoclonal antibodies (mAb) on Cyr61 high expression line MDA-MB-231, known as a highly malignant and invasive human breast cancer cell line, at aspects of proliferation and migration in vitro and in vivo. We found the mAb, denoted as 093G9, revealed inhibitory effects on MDA-MB-231 cell proliferation, migration, and invasion through downregulation of both AKT and ERK phosphorylation in vitro compared with its isotype control. 093G9 also showed significant efficacy on suppressing primary tumor growth and spontaneous lymph node metastasis in in vivo mouse model. The specific epitope recognized by 093G9 was identified to be (140)LPNLGCP(146), adjacent to the VWC domain of Cyr61 by Ph.D.-C7C phage library display system. Our study provides direct evidence that Cyr61 can be a potent therapeutic target for patients who bear high Cyr61 expression breast cancer. Furthermore, the mAb, 093G9 developed in our laboratory, has shown a promising therapeutic characteristic in breast cancer. PMID- 22048718 TI - Neurally adjusted ventilatory assist in patients with critical illness-associated polyneuromyopathy. AB - PURPOSE: Diaphragmatic electrical activity (EA(di)), reflecting respiratory drive, and its feedback control might be impaired in critical illness-associated polyneuromyopathy (CIPM). We aimed to evaluate whether titration and prolonged application of neurally adjusted ventilatory assist (NAVA), which delivers pressure (P (aw)) in proportion to EA(di), is feasible in CIPM patients. METHODS: Peripheral and phrenic nerve electrophysiology studies were performed in 15 patients with clinically suspected CIPM and in 14 healthy volunteers. In patients, an adequate NAVA level (NAVAal) was titrated daily and was implemented for a maximum of 72 h. Changes in tidal volume (V (t)) generation per unit of EA(di) (V (t)/EA(di)) were assessed daily during standardized tests of neuro ventilatory efficiency (NVET). RESULTS: In patients (median [range], 66 [44-80] years), peripheral electrophysiology studies confirmed CIPM. Phrenic nerve latency (PNL) was prolonged and diaphragm compound muscle action potential (CMAP) was reduced compared with healthy volunteers (p < 0.05 for both). NAVAal could be titrated in all but two patients. During implementation of NAVAal for 61 (37-64) h, the EA(di) amplitude was 9.0 (4.4-15.2) MUV, and the V (t) was 6.5 (3.7-14.3) ml/kg predicted body weight. V (t), respiratory rate, EA(di), PaCO(2), and hemodynamic parameters remained unchanged, while PaO(2)/FiO(2) increased from 238 (121-337) to 282 (150-440) mmHg (p = 0.007) during NAVAal. V (t)/EA(di) changed by -10 (-46; +31)% during the first NVET and by -0.1 (-26; +77)% during the last NVET (p = 0.048). CONCLUSION: In most patients with CIPM, EA(di) and its feedback control are sufficiently preserved to titrate and implement NAVA for up to 3 days. Whether monitoring neuro-ventilatory efficiency helps inform the weaning process warrants further evaluation. PMID- 22048719 TI - Epidemiology of contrast-associated acute kidney injury in ICU patients: a retrospective cohort analysis. AB - PURPOSE: Intensive care unit (ICU) patients frequently undergo contrast-enhanced radiographic examinations, which carries a risk for development of contrast associated acute kidney injury (CA-AKI). Data on this in ICU patients are scarce. The aim of this study was therefore to evaluate the epidemiology and short- and long-term outcomes of CA-AKI in ICU patients. METHODS: A retrospective single centre cohort study covering the period 1 March 2004 to 31 December 2008 on ICU patients who underwent a radiography examination with parenteral administration of iodinated radio contrast media was conducted. Data analysis included univariate and multivariate analyses of patients with and without CA-AKI. RESULTS: A total of 787 ICU patients were included in the study. CA-AKI occurred in 128 (16.3%) and was associated with higher need for RRT [30 (4.6%) vs. 21 (16.4%), p < 0.001], worse kidney function at discharge, longer length of ICU and hospital stay, and higher 28-day and 1-year mortality [28-day: 86 (13.1%) vs. 46 (35.9%), p < 0.001, and 1-year: 158 (24.0%) vs. 71 (55.5%), p < 0.001]. Higher serum creatinine, lower mean arterial pressure, and administration of diuretics and vasoactive therapy were associated with development of CA-AKI in multivariate analysis. After correction for confounders we found that CA-AKI was associated with 28-day mortality in this cohort of ICU patients (odds ratio = 2.742, 95% confidence interval 1.374-5.471). CONCLUSIONS: CA-AKI occurred in one out of six ICU patients who underwent a contrast-enhanced radiography examination and was associated with both short-and long-term worse outcomes such as need for RRT, worse kidney function at discharge, increased length of stay in the ICU and hospital, and mortality. PMID- 22048720 TI - Radiocontrast-induced acute kidney injury in the ICU: worse than presumed? PMID- 22048722 TI - The activity of the primary motor cortex ipsilateral to the exercising hand decreases during repetitive handgrip exercise. AB - The brain function controlling muscle force production is not yet fully understood. The purpose of this study was to examine bilateral primary motor cortex (M1) oxygenation during static-handgrip exercises performed with the right hand (60% maximal voluntary contraction; 10 s exercise/75 s rest; five sets). Twelve healthy, right-handed male subjects participated in this study. Near infrared spectroscopy probes were positioned over the bilateral M1 to measure cortical oxygenation during handgrip exercises. The maximum values of the changes in concentrations of oxyhemoglobin (HbO(2)) and deoxyhemoglobin (Hb) across the trials (i) did not change significantly during the contralateral M1 activation (p > 0.05), whereas (ii) in the case of the ipsilateral M1 activation a significant (p < 0.05) decrease in HbO(2) and a significant (p < 0.01) decrease in Hb could be measured. The activation in ipsilateral M1 at the fifth trial was significantly decreased compared with that in the first trial (HbO(2): p < 0.001; Hb: p < 0.001). The present results suggest that the ipsilateral M1 is recruited during the motor task in compensation for the contralateral M1 and the habituation to motor task might alter the efficiency for interaction of the ipsilateral M1 to the contralateral M1. The interhemispheric interaction might change due to habituation to motor task. PMID- 22048721 TI - Site-specific structural analysis of a yeast prion strain with species-specific seeding activity. AB - Prion proteins misfold and aggregate into multiple infectious strain variants that possess unique abilities to overcome prion species barriers, yet the structural basis for the species-specific infectivities of prion strains is poorly understood. Therefore, we have investigated the site-specific structural properties of a promiscuous chimeric form of the yeast prion Sup35 from Saccharomyces cerevisiae and Candida albicans. The Sup35 chimera forms two strain variants, each of which selectively infect one species but not the other. Importantly, the N-terminal and middle domains of the Sup35 chimera (collectively referred to as Sup35NM) contain two prion recognition elements (one from each species) that regulate the nucleation of each strain. Mutations in either prion recognition element significantly bias nucleation of one strain conformation relative to the other. Herein, we have investigated the folding of each prion recognition element for the serine-to-arginine mutant at residue 17 of Sup35NM chimera known to promote nucleation of C. albicans strain conformation. Using cysteine-specific labeling analysis, we find that residues in the C. albicans prion recognition element are solvent-shielded, while those outside the recognition sequence (including most of those in the S. cerevisiae recognition element) are solvent-exposed. Moreover, we find that proline mutations in the C. albicans recognition sequence disrupt the prion templating activity of this strain conformation. Our structural findings reveal that differential folding of complementary and non-complementary prion recognition elements within the prion amyloid core of the Sup35NM chimera is the structural basis for its species specific templating activity. PMID- 22048723 TI - The kallikrein-kinin system and oxidative stress. AB - PURPOSE OF REVIEW: The kallikrein-kinin system (KKS) constitutes a complex multienzyme cascade that produces several bioactive kinin peptides and their derivatives including bradykinin. In addition to the classical notion of the KKS as a potent vasodilator and a mediator of inflammatory responses, recent studies suggest a link between the KKS and oxidative stress. A number of established mouse models with altered levels of KKS components opened the way to evaluate precise functions of the KKS. Here we review recent findings on the role of the KKS in cardiovascular diseases and chronic kidney diseases, and discuss potential benefits of KKS activation in these diseases. RECENT FINDINGS: Deletion of both B1R and B2R in a diabetic mouse model exacerbates its renal phenotypes, suggesting that the KKS exerts protective effects on diabetic nephropathy by suppressing oxidative stress, presumably via nitric oxide and prostaglandins. SUMMARY: Accumulating evidence has highlighted the importance of the KKS as a protective system against oxidative stress and organ damage in the heart and kidney. The activation of the KKS by angiotensin I-converting enzyme inhibitors and vasopeptidase inhibitors is likely to be beneficial in senescence-associated cardiovascular diseases and chronic kidney diseases. PMID- 22048724 TI - Nitric oxide synthase derangements and hypertension in kidney disease. AB - PURPOSE OF REVIEW: Nitric oxide deficiency occurs by multiple mechanisms and contributes to the pathogenesis of progression of chronic kidney disease (CKD) and its cardiovascular complications. This article concentrates on recent developments on the regulation of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in CKD and on the importance of the nitric oxide synthases in kidney disease progression, particularly in diabetic nephropathy. RECENT FINDINGS: The increased plasma ADMA seen in renal disease is generally predictive of severity of CKD progression and cardiovascular risk. However, some assumptions about the control of ADMA have been challenged: the primacy of the kidney as a metabolic organ for plasma ADMA regulation has come under scrutiny and the relative importance of the two isoforms of the ADMA metabolizing enzymes dimethylarginine dimethylaminohydrolases (DDAHs) is being re evaluated. Alterations in NOS also contribute to CKD progression with the endothelial isoform playing a major role in diabetic nephropathy. SUMMARY: Improving our understanding of ADMA regulation is important since pharmacologic targeting of DDAH is underway. The major role of endothelial NOS-derived nitric oxide in diabetic nephropathy should lead to novel therapies. The beneficial actions of dietary nitrate supplementation on blood pressure and kidney disease are of considerable clinical relevance. PMID- 22048725 TI - A feeding inhibition based prediction of the toxic effect of dissolved metal mixtures upon Echinogammarus marinus (Crustacea: Amphipoda) at field relevant concentrations across a latitudinal gradient. AB - Risk assessment of metals in the environment is performed mainly with toxicity evaluations on single metals, which is largely inadequate since these substances occur in mixtures. The development of models predicting combined toxic effects on the basis of the concentration-response relationships of individual compounds has emerged as an answer. In the present study, metal effects on post-exposure anorexia (the concept of FdC(50)--concentration causing 50% of feeding inhibition -is implemented) in Echinogammarus marinus, a widely distributed gammarid amphipod, were assessed and compared with modelled ones obtained through the application of the concentration addition (CA) model, which represents a reasonable worst-case scenario for the risk assessment of metal mixtures. Data were validated using in situ experiments performed along a latitudinal gradient (Iceland, Scotland and Portugal) aiming at establishing a geographic profile of autochthonous population susceptibilities to metals. For all of the metals studied concentrations in the water column at exposure sites were in good agreement with feeding inhibition levels. Models gave low to relatively high percentage agreement between predictions and experimental data. Boreal populations demonstrated higher susceptibility to single metals, but not to mixture exposures. Meridional populations denoted lower susceptibilities with higher FdC(50). PMID- 22048726 TI - The specific vibrational modes of GTP in solution and bound to Ras: a detailed theoretical analysis by QM/MM simulations. AB - The hydrolysis of guanosine triphosphate (GTP) in general, and especially by GTPases like the Ras protein, is in the focus of biological investigations. A huge amount of experimental data from Fourier-transformed infrared studies is currently available, and many vibrational bands of free GTP, GTP.Mg(2+), and Ras.GTP.Mg(2+) in solution have been assigned by isotopic labeling. In the Ras environment, bands between 800 cm(-1) and 1300 cm(-1) have already been assigned, but not those below 800 cm(-1). The combination of quantum and molecular mechanics (QM/MM) methods takes the quantum effects for selected relevant atoms into account. This provides structural details, vibrational frequencies and electron distributions of the region of interest. We therefore used MM and QM/MM simulations to investigate the normal vibrational modes of GTP, GTP.Mg(2+), and Ras.GTP.Mg(2+) in solution, and assigned the vibrational frequencies for each normal vibration mode. In this study, the quantum box contains the nucleoside and the Mg(2+). The comparison of calculated and experimental vibrational spectra provides a very good control for the quality of the calculations. Structurally, MM and QM/MM simulations reveal a stable tridentate coordination of the Mg(2+) by GTP in water, and a stable bidentate coordination by GTP in complex with Ras. For validation, we compare the calculated frequencies and isotopic shifts with the experimental results available in the range of 800 cm(-1) to 1300 cm(-1). For the first time we suggest band assignments of the vibrational modes below 800 cm(-1) by comparison of calculated and experimental spectra. PMID- 22048728 TI - Invasive pneumococcal disease and 13-valent pneumococcal conjugate vaccine (PCV13) coverage among children aged <=59 months---selected U.S. regions, 2010- 2011. AB - On March 12, 2010, the Advisory Committee on Immunization Practices (ACIP) published recommendations for use of a newly licensed, 13-valent pneumococcal conjugate vaccine (PCV13) to replace the 7-valent vaccine (PCV7) for all children and for a supplemental dose for those aged 14 through 59 months. PCV is given routinely to children at ages 2, 4, and 6 months, and a booster dose is given at 12--15 months. PCV13 includes antigens of six pneumococcal serotypes in addition to those in PCV7. Children only vaccinated with PCV7 are susceptible to those six serotypes, which can cause invasive pneumococcal disease (IPD) and death. During 2010 and 2011, CDC evaluated available data to assess the occurrence of PCV13 type IPD cases and PCV13 vaccination coverage among children aged <=59 months. During May 1, 2010--April 30, 2011, 63 vaccine-eligible children with IPD caused by a serotype that would have been prevented by PCV13 were identified within 12 study regions. Most of those children were aged 24 through 59 months and were vaccinated completely with PCV7 but had not received the recommended supplemental dose of PCV13. Immunization Information System (IIS) sentinel site data from March 2010--June 2011 indicated that the proportion of PCV7-vaccinated children who had received the PCV13 supplemental dose was only 37%. Similarly, among children aged <=59 months requiring additional primary series doses, PCV13 coverage was only 46%. Given the potential for missed PCV13 vaccination, health care providers should recommend PCV13 vaccination for all eligible children aged 14 through 59 months during all visits, and continue to ensure receipt of the full PCV13 primary series for younger children. PMID- 22048727 TI - Genetics of GABAergic signaling in nicotine and alcohol dependence. AB - Both nicotine and alcohol addictions are common chronic brain disorders that are of great concern to individuals and society. Although genetics contributes significantly to these disorders, the susceptibility genes and variants underlying them remain largely unknown. Many years of genome-wide linkage and association studies have implicated a number of genes and pathways in the etiology of nicotine and alcohol addictions. In this communication, we focus on current evidence, primarily from human genetic studies, supporting the involvement of genes and variants in the GABAergic signaling system in the etiology of nicotine dependence and alcoholism based on linkage, association, and gene-by-gene interaction studies. Current efforts aim not only to replicate these findings in independent samples, but also to identify which variant contributes to the detected associations and through what molecular mechanisms. PMID- 22048729 TI - Progress toward poliomyelitis eradication---India, January 2010--September 2011. AB - The Global Polio Eradication Initiative was launched in 1988. In 1995, when eradication activities were initiated in India, an estimated 50,000 polio cases were occurring each year. By 2006, transmission of indigenous wild poliovirus (WPV) had been interrupted in all countries except India, Afghanistan, Pakistan, and Nigeria. During 2006--2009, India annually reported 559 to 874 cases of confirmed WPV, with cases centered in the northern states of Uttar Pradesh and Bihar. These cases accounted for 43% of confirmed cases of WPV reported worldwide during this period. However, in 2010, only 42 WPV cases were reported in India, and in 2011, only one WPV case had been confirmed as of October 31. This report updates previous reports and summarizes progress toward polio eradication in India during January 2010--September 2011. Throughout India, the most recent confirmed WPV type 3 (WPV3) case occurred on October 22, 2010, in Jharkhand, and the most recent confirmed WPV type 1 (WPV1) case occurred on January 13, 2011, in West Bengal; WPV2 has not been reported in India since 1999. Importation of WPV into India is a risk, and undetected low-level WPV transmission is a possibility, requiring high vaccination coverage in all states, continued focus on children in migrant and underserved populations, sensitive surveillance for prompt detection of any WPV, and preparedness to mount a robust emergency vaccination campaign in response to any WPV cases. PMID- 22048730 TI - Vital signs: overdoses of prescription opioid pain relievers---United States, 1999--2008. AB - BACKGROUND: Overdose deaths involving opioid pain relievers (OPR), also known as opioid analgesics, have increased and now exceed deaths involving heroin and cocaine combined. This report describes the use and abuse of OPR by state. METHODS: CDC analyzed rates of fatal OPR overdoses, nonmedical use, sales, and treatment admissions. RESULTS: In 2008, drug overdoses in the United States caused 36,450 deaths. OPR were involved in 14,800 deaths (73.8%) of the 20,044 prescription drug overdose deaths. Death rates varied fivefold by state. States with lower death rates had lower rates of nonmedical use of OPR and OPR sales. During 1999--2008, overdose death rates, sales, and substance abuse treatment admissions related to OPR all increased substantially. CONCLUSIONS: The epidemic of overdoses of OPR has continued to worsen. Wide variation among states in the nonmedical use of OPR and overdose rates cannot be explained by underlying demographic differences in state populations but is related to wide variations in OPR prescribing. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Health-care providers should only use OPRs in carefully screened and monitored patients when non-OPR treatments are insufficient to manage pain. Insurers and prescription drug monitoring programs can identify and take action to reduce both inappropriate and illegal prescribing. Third-party payers can limit reimbursement in ways that reduce inappropriate prescribing, discourage efforts to obtain OPR from multiple health-care providers, and improve clinical care. Changes in state laws that focus on the prescribing practices of health-care providers might reduce prescription drug abuse and overdoses while still allowing safe and effective pain treatment. PMID- 22048731 TI - Human dermis harbors distinct mesenchymal stromal cell subsets. AB - Multipotent mesenchymal stromal cells (MSCs) are found in a variety of adult tissues including human dermis. These MSCs are morphologically similar to bone marrow-derived MSCs, but are of unclear phenotype. To shed light on the characteristics of human dermal MSCs, this study was designed to identify and isolate dermal MSCs by a specific marker expression profile, and subsequently rate their mesenchymal differentiation potential. Immunohistochemical staining showed that MSC markers CD73/CD90/CD105, as well as CD271 and SSEA-4, are expressed on dermal cells in situ. Flow cytometric analysis revealed a phenotype similar to bone marrow-derived MSCs. Human dermal cells isolated by plastic adherence had a lower differentiation capacity as compared with bone marrow derived MSCs. To distinguish dermal MSCs from differentiated fibroblasts, we immunoselected CD271(+) and SSEA-4(+) cells from adherent dermal cells and investigated their mesenchymal differentiation capacity. This revealed that cells with increased adipogenic, osteogenic, and chondrogenic potential were enriched in the dermal CD271(+) population. The differentiation potential of dermal SSEA 4(+) cells, in contrast, appeared to be limited to adipogenesis. These results indicate that specific cell populations with variable mesenchymal differentiation potential can be isolated from human dermis. Moreover, we identified three different subsets of dermal mesenchymal progenitor cells. PMID- 22048732 TI - The growth of clinical trials and systematic reviews in informing dermatological patient care. AB - Randomized controlled clinical trials remain the best method for minimizing bias when evaluating dermatological treatments. Many dermatologic clinical trials have suffered from small sample sizes, selective reporting of outcomes, publication bias, poor reporting, and heterogeneous outcomes that have hampered comparability deficiencies that can be overcome by adopting good trial planning and reporting practice encouraged by this journal. Although a profusion of explanatory placebo controlled studies have contributed little to decision making in the clinical setting, some comparative effectiveness trials such as the use of topical corticosteroids for pemphigoid may have played a pivotal role in improving the well-being of dermatological patients. Systematic reviews (SRs) of clinical trials strive to organize the entire body of evidence while minimizing bias so that policy makers and guideline developers can base their recommendations on the appropriate strength and level of evidence. In dermatology, SRs, such as those undertaken by the Cochrane Collaboration, have produced clear clinical messages despite conflicting individual studies, and also play a key role in identifying research gaps. Future challenges include optimizing the use of research resources, adopting methodological developments in health technology assessment, and prospective registration and complete reporting of all study results. PMID- 22048733 TI - Koebner phenomenon in psoriasis is not associated with deletion of late cornified envelope genes LCE3B and LCE3C. PMID- 22048735 TI - Predicting Michael-acceptor reactivity and toxicity through quantum chemical transition-state calculations. AB - The electrophilic reactivity of Michael acceptors is an important determinant of their toxicity. For a set of 35 alpha,beta-unsaturated aldehydes, ketones and esters with experimental rate constants of their reaction with glutathione (GSH), k(GSH), quantum chemical transition-state calculations of the corresponding Michael addition of the model nucleophile methane thiol (CH(3)SH) have been performed at the B3LYP/6-31G** level, focusing on the 1,2-olefin addition pathway without and with initial protonation. Inclusion of Boltzmann-weighting of conformational flexibility yields intrinsic reaction barriers DeltaE(?) that for the case of initial protonation correctly reflect the structural variation of k(GSH) across all three compound classes, except that they fail to account for a systematic (essentially incremental) decrease in reactivity upon alpha substitution. By contrast, the reduction in k(GSH) through beta-substitution is well captured by DeltaE(?). Empirical correction for the alpha-substitution effect yields a high squared correlation coefficient (r(2) = 0.96) for the quantum chemical prediction of log k(GSH), thus enabling an in silico screening of the toxicity-relevant electrophilicity of alpha,beta-unsaturated carbonyls. The latter is demonstrated through application of the calculation scheme for a larger set of 46 Michael-acceptor aldehydes, ketones and esters with experimental values for their toxicity toward the ciliates Tetrahymena pyriformis in terms of 50% growth inhibition values after 48 h exposure (EC(50)). The developed approach may add in the predictive hazard evaluation of alpha,beta-unsaturated carbonyls such as for the European REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) Directive, enabling in particular an early identification of toxicity-relevant Michael-acceptor reactivity. PMID- 22048734 TI - CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice. AB - The antagonism of CXC-chemokine receptor 4 (CXCR4) with AMD3100 improves cardiac performance after myocardial infarction by augmenting the recruitment of endothelial progenitor cells (EPCs) from the bone marrow to the regenerating vasculature. We investigated whether AMD3100 may accelerate diabetes-impaired wound healing through a similar mechanism. Skin wounds were made on the backs of leptin receptor-deficient mice and treated with AMD3100 or saline. Fourteen days after treatment, wound closure was significantly more complete in AMD3100-treated mice (AMD3100: 87.0 +/- 2.6%, saline: 33.1 +/- 1.8%; P<0.0001) and was accompanied by greater collagen fiber formation, capillary density, smooth muscle containing vessel density, and monocyte/macrophage infiltration. On day 7 after treatment, AMD3100 was associated with higher circulating EPC and macrophage counts, and with significantly upregulated mRNA levels of stromal cell-derived factor 1 and platelet-derived growth factor B in the wound bed. AMD3100 also promoted macrophage proliferation and phagocytosis and the migration and proliferation of diabetic mouse primary dermal fibroblasts and 3T3 fibroblasts, which express very little CXCR4. In conclusion, a single topical application of AMD3100 promoted wound healing in diabetic mice by increasing cytokine production, mobilizing bone marrow EPCs, and enhancing the activity of fibroblasts and monocytes/macrophages, thereby increasing both angiogenesis and vasculogenesis. Not all of the AMD3100-mediated effects evolved through CXCR4 antagonism. PMID- 22048736 TI - Magnetic resonance imaging: fundamental safety issues. AB - SYNOPSIS: Medical practitioners have a variety of imaging modalities at their disposal. The exquisite soft tissue delineation available with magnetic resonance imaging (MRI) has resulted in the rising utilization of this particular modality. Increasingly, physical therapists around the world are actively involved in not only referring patients with musculoskeletal conditions for MRI but also in the acquisition of MRI data in both the clinical and research arenas. The MRI process involves the use of a very strong static magnetic field, time-varying (gradient) fields, and radiofrequency energy. To ensure the well-being of patients, staff, and visitors, an understanding of the primary hazards of this environment and the rigorous safety procedures that must be followed is imperative to the clinician. This paper describes the basic components of an MRI system, discusses various MRI safety issues, and presents the screening procedure necessary prior to using MRI. Primary hazards associated with the imaging process are also reviewed. J Orthop Sports Phys Ther 2011;41(11):820-828. doi:10.2519/jospt.2011.3906. PMID- 22048738 TI - Tackling antibiotic resistance. AB - The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable but can nevertheless be controlled, and it must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011. From these discussions there emerged a priority list of steps that need to be taken to resolve this global crisis. PMID- 22048737 TI - Actin organization and dynamics in filamentous fungi. AB - Growth and morphogenesis of filamentous fungi is underpinned by dynamic reorganization and polarization of the actin cytoskeleton. Actin has crucial roles in exocytosis, endocytosis, organelle movement and cytokinesis in fungi, and these processes are coupled to the production of distinct higher-order structures (actin patches, cables and rings) that generate forces or serve as tracks for intracellular transport. New approaches for imaging actin in living cells are revealing important similarities and differences in actin architecture and organization within the fungal kingdom, and have yielded key insights into cell polarity, tip growth and long-distance intracellular transport. In this Review, we discuss the contribution that recent live-cell imaging and mutational studies have made to our understanding of the dynamics and regulation of actin in filamentous fungi. PMID- 22048739 TI - Viral infection. The gut microbiota: friend or foe? AB - The gut microbiota can facilitate viral infection and transmission. PMID- 22048740 TI - Osteopathy for musculoskeletal pain: a systematic review. PMID- 22048742 TI - Microbial systematics in the post-genomics era. AB - Microbial systematics and phylogeny should form the foundation and guiding light for a comprehensive understanding of different aspects of microbiology. However, there are many critical issues in microbial systematics that are currently not resolved. Some of these include: how to define and delimit a prokaryotic species; development of rationale criteria for the assignment of higher taxonomic ranks; understanding what unique properties distinguish species from different groups; and understanding the branching order and interrelationship among higher prokaryotic clades. The sequencing of genomes from large numbers of cultured as well as uncultured microbes covering prokaryotic diversity provides unique means to achieve these important objectives. Prokaryotic genomes are found to be very diverse and dynamic and horizontal gene transfers (HGTs) are indicated to have played important role in species/genome evolution. Although HGT adds a layer of complexity in terms of understanding the genomes and species evolution, it is contended that vast majority of genes and genetic characteristics that are distinctive characteristics of higher prokaryotic taxa are vertically inherited and based on them a solid foundation for microbial systematics can be developed. We describe two kinds of molecular markers consisting of conserved indels in protein sequences and whole proteins that are specific for different groups that are proving particularly valuable in defining different prokaryotic groups in clear molecular terms and in understanding their interrelationships. The genetic and biochemical studies on these taxa-specific molecular markers also open the way to discover novel biochemical and physiological characteristics that are unique properties of these groups. PMID- 22048741 TI - Long-term efficacy of a short period of taping followed by an exercise program in a cohort of patients with patellofemoral pain syndrome. AB - Patellofemoral pain syndrome (PFPS) is a common source of anterior knee pain. While treatment for PFPS may be successful in the short term, long-term results are less promising. The purpose of this study was to record long-term pain and functionality outcomes following rehabilitation in patients affected by PFPS. A prospective cohort study of 44 patients with a diagnosis of PFPS and an activation imbalance between the vastus medialis obliquus (VMO) and vastus lateralis (VL) muscles were enrolled. Patients underwent patellar taping (2 weeks) followed by a rehabilitation program lasting until the end of the third month. Primary outcome measures were pain and the functional level of the patellofemoral joint. Secondary outcome measures were surface electromyographic (sEMG) onset timing of the VMO/VL during seated knee extension and squat and isometric knee extensor muscle strength. Significant differences in all the outcome measures were observed between the affected and unaffected sides before treatment. The pain score significantly decreased both posttreatment (Delta = 4.7; 95% CI = -5.4 to -3.9) and at the 12-month follow-up (Delta = -5.5; 95% CI = -6.1 to -4.8), while the functional level significantly increased both posttreatment (Delta = 24; 95% CI = 18.3 to 30.2) and at the 12-month follow-up (Delta = 26; 95% CI = 21.4 to 30.6). Posttreatment, 35/44 patients (79.5%) and 31/44 patients (70.5%) achieved normal sEMG onset timing of the VMO and VL in the seated knee extension exercise and in the squat exercise, respectively. A short period of patellar taping followed by an exercise program results in long-lasting pain control in PFPS associated with muscular dysfunction. PMID- 22048744 TI - Comprehensive risk reduction in patients with atrial fibrillation: Emerging diagnostic and therapeutic options. Executive summary of the report from the 3rd AFNET/EHRA consensus conference. AB - There are exciting new developments in several areas of atrial fibrillation (AF) management that carry the hope of improving outcomes in AF patients. This paper is an executive summary that summarises the proceedings from the 3rd AFNET/EHRA consensus conference on atrial fibrillation, held in Sophia Antipolis from November 7th to 9th 2010, shortly after the release of the new ESC guidelines on AF. The conference was jointly organised by the German Atrial Fibrillation competence NETwork (AFNET) and the European Heart Rhythm Association (EHRA). This executive summary report covers four sections: 1. Risk factors and risk markers for AF, 2. Pathophysiological classification of AF, 3. Relevance of monitored AF duration for AF-related outcomes, and 4. Perspectives and needs for implementing better antithrombotic therapy. PMID- 22048745 TI - See the whole picture: knee preserving therapy needs more than surface repair. PMID- 22048746 TI - Bone-patellar tendon-bone autograft versus hamstring autograft anterior cruciate ligament reconstruction in the young athlete: a retrospective matched analysis with 2-10 year follow-up. AB - PURPOSE: The aim of this study was to examine clinical and patient-reported outcomes as well as return to sport in athletes younger than 25 following ACL reconstruction with either bone-patellar tendon-bone (BTB) or hamstring (HS) autografts using a matched-pairs case-control experimental design. METHODS: Twenty-three matched pairs were obtained based on gender (57% women), age (18 +/- 3 years BTB vs. 18 +/- 3 HS), and length of follow-up (5 +/- 2 years BTB vs. 4 +/ 2 HS). Patients reported participating in very strenuous (soccer, basketball, etc.) or strenuous (skiing, tennis, etc.) sporting activity 4-7 times/week prior to their knee injury. Patient-reported outcomes included return to play data, the IKDC, SAS, ADLS, and SF-36 forms. Clinical outcomes included knee range of motion, laxity, and hop/jump testing. RESULTS: The majority of patients in both groups were able to participate in very strenuous or strenuous sporting activity 4-7 times per week following surgery [17 (74%) BTB vs. 16 (70%) HS]. However, only 13 (57%) of the BTB subjects and 10 (44%) of the HS patients were able to return to pre-injury activity levels (P = n.s.). HS patients showed higher ADLS (P < 0.01) and SAS (P < 0.01) scores, better restoration of extension (P < 0.05), and less radiographic evidence of osteoarthritis (P < 0.05). CONCLUSIONS: Hamstring and bone-patellar tendon-bone autografts allow approximately 70% of young athletes to return to some degree of strenuous or very strenuous sporting activity, while only approximately half of patients were able to return to their pre-injury sporting activity level. Hamstring grafts lead to better preservation of extension, higher patient-reported outcome scores, and less radiographic evidence of osteoarthritis. LEVEL OF EVIDENCE: Therapeutic (case-control study) Level III. PMID- 22048747 TI - Anterior cruciate ligament rupture in gouty arthritis. AB - A 34-year-old male presented with right knee instability without any trauma. He had been diagnosed with right knee gouty arthritis 2 years prior. An arthroscopic examination revealed abundant calcific material deposited around the knee joint, including in the ACL tissue, and that the ACL was torn at the femoral attachment site. Treatment involved a synovectomy to remove calcific material, followed by an ACL reconstruction. Histology evaluation revealed gouty arthritis with the presence of tophi in the synovium, soft tissue, and ACL tissue. The case presented here indicates the possibility of pathologic rupture of the ACL associated with gouty tophus infiltration of that ligament. Level of evidence IV. PMID- 22048748 TI - Arthroscopic treatment of a talar neck fracture: a case report. AB - Talar neck fractures are severe injuries, and their complications can lead to significant functional disability. Open reduction and internal fixation still constitute the treatment of choice. We report a case of a patient with a Hawkins type III talar neck fracture who was treated successfully with the use of an entirely arthroscopic technique. Four arthroscopic portals were used to control fracture reduction and fixation, which was made by two cannulated screws. There were no complications, and the patient returned uneventfully to her previous daily activities. LEVEL OF EVIDENCE: Therapeutic study, Case report with no comparison group, Level IV. PMID- 22048749 TI - Morphometrical measurement of resected surface of medial and lateral proximal tibia for Chinese population. AB - PURPOSE: The objective of this study was to analyze the morphology of the medial tibial plateau and lateral tibial plateau in Chinese knees and compared these measurements and features with those of commercial unicondylar tibial baseplates. METHODS: Three-dimensional knee models were reconstructed from computed tomography slices of 81 subjects. Among the series, 27 knees were from male subjects and 54 knees from female subjects. The dimensions and shape of the medial and lateral tibial plateaus were measured and compared with six commercially available unicondylar tibial baseplates. RESULTS: The results showed significant differences between the shapes of the medial and lateral tibial plateaus. For the lateral tibial plateau, the shape was symmetric about the mediolateral axis. The medial plateaus presented their widest mediolateral width in an obviously more posterior position than the lateral compartment. Additionally, the plateau aspect ratio decreased with increasing mediolateral dimensions, in contrast to the constant aspect ratio shown by conventional unicondylar knee prostheses. CONCLUSION: Compartment-specific designs may optimize coverage between the prosthesis and resected tibial surface. The morphometrical measurements presented may allow manufacturers to design tibial baseplates that accommodate the structural variability between different ethnic groups. LEVEL OF EVIDENCE: Prospective comparative study, Level II. PMID- 22048750 TI - Conductive artificial biofilm dramatically enhances bioelectricity production in Shewanella-inoculated microbial fuel cells. AB - A new strategy of electrogen immobilization was developed to construct a conductive artificial biofilm (CAB) on an anode of a microbial fuel cell (MFC). The MFCs equipped with an optimized CAB exhibited an eleven fold increase in power output compared with natural biofilms. PMID- 22048751 TI - Metformin causes nitric oxide-mediated dilatation in a shorter time than insulin in the iliac artery of the anesthetized pig. AB - We tested the hypothesis that metformin produces arterial dilatation indirectly, by directly exposing the endothelial surface, of an occluded test segment of the pig iliac artery in vivo, to test blood containing metformin or excess insulin, with and without the presence of the nitric oxide (NO) synthase inhibitor NG nitro-L-arginine methyl ester hydrochloride. Such exposure to metformin 1 MUg/mL caused the artery to dilate at constant pressure, and this was abolished when NG nitro-L-arginine methyl ester hydrochloride was coadministered with metformin. The onset of dilatation occurred approximately 4 minutes after the commencement of endothelial exposure to metformin; this contrasts with the approximate 10 minutes required for a similar response to luminal hyperinsulinemia. After the release of flow occlusion, the subsequent flow-mediated dilatation was slightly but significantly enhanced compared with control for metformin; the effect of insulin on flow-mediated dilatation was not statistically significant. The hypothesis was disproved, as we have shown that insulin and metformin, like insulin, directly stimulate NO production by endothelium of a conduit artery; this function may be of value in delaying the atherothrombotic process. The time taken for the commencement of NO production is shorter for metformin than for insulin; the clinical relevance of this finding is unclear. PMID- 22048752 TI - Impacts of age and gender on bone marrow profiles of BMP7, BMPRs and Stro-1+ cells in patients with total hip replacement. AB - PURPOSE: A successful osseointegration relies on the interplay of implant surface and surrounding bone marrow cells. This study was undertaken to investigate the impact of age and gender on the bone marrow composition. METHODS: Bone marrow aspirates were obtained from the discarded metaphysis region of the femoral head in 24 patients with total hip replacement. Flow cytometry was used to measure the expression of Stro-1(+) cells and BMP receptors (BMPRs)-expressing cells. ELISA was used to measure bone marrow aspirate bone morphology protein7 (BMP7) concentration. RESULTS: Our data demonstrates that there are diverse bone marrow profiles (Stro-1(+) cell and BMPRs(+) cells). There are no differences of Stro 1(+) cells, BMPRs(+) cells, and BMP7 concentration between male and female patients. Though there are slight increases in the number of Stro-1(+) cells and BMPRs(+) cells in younger patients (<70 years old) than those of old patients (>= 70 years old), the difference is not statistically significant. However, we found a close association between the Stro-1(+) cells, BMPR1a cells and BMP7 concentration. In addition, a correlation exists between the number of Stro-1(+) cells and BMIs of these patients. CONCLUSION: Our data suggests that the age and gender of THR patients have little impact on their bone marrow osteogenic potential. The significance of the number of the Stro-1(+) with BMPRs expression on the implant fixation and osseointegration warrants further investigation. PMID- 22048753 TI - Adverse reactions and events related to musculoskeletal allografts: reviewed by the World Health Organisation Project NOTIFY. AB - PURPOSE: The use of bone and connective tissue allografts has grown rapidly and surpassed the use of autografts in many countries. Being of human origin, bone and tendon allografts carry the risk of disease transmission and complications have been reported. As part of the Project NOTIFY led by the World Health Organisation, an effort to improve recognition, reporting, tracking and investigation of adverse outcomes of allografts was initiated, achieving a comprehensive review of associated disease transmission and failures. Those involving the use of musculoskeletal allografts are reported here. A major objective is to involve orthopaedic surgeons in the improvement of the safe use of the musculoskeletal allografts. METHODS: We reviewed the medical literature, requested reports from surgeons in selected professional organisations and informally surveyed tissue bank organisations and selected tissue bank professionals to discover reported and unreported cases of adverse outcomes. We analysed each case to decide the likelihood that the complication was truly allograft related. RESULTS: The efficiency of the procedures involved in bone banking and bone and tendon allograft has improved significantly during the last three decades. The evolution of the incidence of reported adverse reactions and events reflects positively on the safety of transplanted tissues. Cases of bacterial and viral transmission by bone and tendon allografts occurred mainly with those that contained viable cells, were not processed to remove cells, or were not disinfected or sterilised. We documented cases of transmission of human immunodeficiency virus (HIV), hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), unspecified hepatitis, tuberculosis and other bacteria. Reporting of these adverse outcomes has led to corrective actions and has significantly improved the safety of allograft use. However, it is probable that not all cases have been reported and investigated. CONCLUSIONS: Considering the high quality standards achieved in many countries, the best approach for further improvement in the safety of allografts is through a systematic reporting of all serious adverse reactions and events in the context of a global biovigilance programme. PMID- 22048754 TI - One Journey's End. PMID- 22048755 TI - Promoting mother's milk use in very low birth weight infants: when nutritional hierarchy deals with the professional value system. PMID- 22048756 TI - Effect of warm breastshields on breast milk pumping. AB - The effect of using a warm breastshield on the efficiency, effectiveness, and comfort of expressing milk with an electric breast pump was assessed. The authors tested a standard breastshield at 25 degrees C and a breastshield warmed to 39 degrees C on 25 mothers using their maximum comfortable vacuum or -125 mm Hg. Using a warm breastshield effectively warmed the nipple and areola and, combined with maximum comfortable vacuum, decreased the time to remove 80% of the total milk yield and increased the percentage of available milk removed after 5 minutes of expression, with no change in the percentage of available milk removed after 15 minutes of expression compared with an ambient-temperature breastshield. The data confirmed that use of the mother's maximum comfortable vacuum was more efficient than a vacuum of -125 mm Hg. Using a warm breastshield with an electric breast pump was comfortable and improved the efficiency of milk removal. PMID- 22048757 TI - Development of a postnatal educational program for breastfeeding mothers in community settings: intervention mapping as a useful guide. AB - Inconsistency in how professionals can best support the breastfeeding mother after discharge call on further investigation. The authors describe how intervention mapping was used to develop a postnatal breastfeeding support intervention for mothers in community settings. Breastfeeding cessation most often occurred in the first weeks among mothers with low self-efficacy, low confidence, or limited previous breastfeeding experience. Besides learning effective breastfeeding techniques, mothers needed to learn how to recognize their baby's cues, let the baby regulate meals, gain confidence in producing enough milk, and handle breastfeeding problems. Theory-based methods-such as individualization, skills training with guided practice, reattribution, planning coping responses, and mobilizing social support-were built into a health visitor delivered program. An 18-hour training course addressed determinants for implementation. Finally, process and effect evaluations were planned. Support of the breastfeeding mother in community settings should address the psychosocial and practical aspects of breastfeeding to prevent premature cessation. PMID- 22048758 TI - American Academy of Pediatrics Section on Breastfeeding. AB - The Section on Breastfeeding is one of 50 sections of the American Academy of Pediatrics. In this Physicians' Focus, we describe the mission, vision, and activities of the Section on Breastfeeding and the benefits it provides to patients, health care professionals, and the general public. We also highlight opportunities to participate in the section. PMID- 22048759 TI - A mother with glandular hypoplasia and a late preterm infant. AB - This case study presents a maternal-infant dyad, both of whom bring risk factors to the breastfeeding relationship. The mother had true glandular hypoplasia that was not detected in the antenatal period or during her hospital stay. In addition, the infant was a late preterm infant, bringing the risks of poor feeding behavior and ineffective removal of milk from the breast as well as limited body reserves. Through the use of breastfeeding technology, including test weights, use of a hospital grade double electric breast pump and use of a nipple shield, in addition to a pharmacologic intervention, in which Domperidone was administered, this mother was able to maximize her milk yield and the infant was able to receive human milk for 6 months. This case report highlights the need for a thorough assessment of the breasts as well as the breastfeeding process in all breastfeeding dyads. PMID- 22048760 TI - Helping your baby with torticollis. PMID- 22048762 TI - New evidence: exclusive breastfeeding and reduced sudden infant death syndrome risk. PMID- 22048763 TI - Structural variability and dynamics of the P3HT/PCBM interface and its effects on the electronic structure and the charge-transfer rates in solar cells. AB - Using a range of realistic interface geometries obtained from a molecular dynamics simulation we study the effects of different microscopic atomic arrangements on the electronic structure and charge transfer rates of the prototypical photovoltaic interface between P3HT (poly(3-hexylthiophene)) and PCBM ([6,6]-phenyl-C(61)-butyric acid methyl ester). The electronic structures of charge-transfer (CT) states belong to two groups that can be denoted as "charge separated" and "charge-bridging" states. For the former group of structures, which may lead to fully separated charges, the ranges and the average values of internal reorganization energy, the electronic coupling and the charge separated states energy are evaluated. A range and distribution of absolute charge separation (CS) and recombination (CR) rates are computed using the Marcus-Levich Jortner rate equation. Due to the variety of P3HT/PCBM interface structures, a very broad range of CS (7.7 * 10(9)-1.8 * 10(12) s(-1)) and CR (2.5 * 10(5)-1.1 * 10(10) s(-1)) "instantaneous" rates are computed. However, the energetic parameters affecting the rate evolve in time due to the dynamic nature of the interface with a characteristic timescale of about 10 ns. For this reason the slowest CR instantaneous rates are not observed and the minimum CR rate observed is determined by the rate of conformational rearrangement at the interface. The combination of these observations provides a more general framework for the interpretation of experimental spectroscopic data, suggesting that the analysis based on simple first order rates may be insufficient to describe charge transfer in organic solar cell interfaces. PMID- 22048764 TI - Human Th1 and Th17 cells exhibit epigenetic stability at signature cytokine and transcription factor loci. AB - The linear model of Th cell lineage commitment is being revised due to reports that mature Th cells can trans-differentiate into alternate lineages. This ability of Th cells to reprogram is thought to be regulated by epigenetic mechanisms that control expression of transcription factors characteristic of opposing lineages. It is unclear, however, to what extent this new model of Th cell plasticity holds true in human Th cell subsets that develop under physiological conditions in vivo. We isolated in vivo-differentiated human Th1 and Th17 cells, as well as intermediate Th1/17 cells, and identified distinct epigenetic signatures at cytokine (IFNG and IL17A) and transcription factor (TBX21, RORC, and RORA) loci. We also examined the phenotypic and epigenetic stability of human Th17 cells exposed to Th1-polarizing conditions and found that although they could upregulate TBX21 and IFN-gamma, this occurred without loss of IL-17 or RORC expression, and resulted in cells with a Th1/17 phenotype. Similarly, Th1 cells could upregulate IL-17 upon enforced expression of RORC2, but did not lose expression of IFN-gamma or TBX21. Despite alterations in expression of these signature genes, epigenetic modifications were remarkably stable aside from the acquisition of active histone methylation marks at cytokine gene promoters. The limited capacity of human Th17 and Th1 cells to undergo complete lineage conversion suggests that the bipotent Th1/17 cells may arise from Th1 and/or Th17 cells. These data also question the broad applicability of the new model of Th cell lineage plasticity to in vivo-polarized human Th cell subsets. PMID- 22048765 TI - Characterization of a human cervical CD4+ T cell subset coexpressing multiple markers of HIV susceptibility. AB - The HIV pandemic disproportionately affects women, with most infections acquired through receptive vaginal sex. Although the target cells by which HIV establishes infection in the female genital tract remain poorly defined, it is known that immune activation results in CD4(+) T cells with enhanced susceptibility, as does expression of the mucosal integrin alpha4beta7 and the HIV coreceptor CCR5. Blood and cervical cytobrush specimens were collected from female sex workers (FSWs) in Nairobi, Kenya. Genital infection diagnostics were performed, T cell populations were defined by multiparameter flow cytometry based on their expression of surface receptors relevant to mucosal homing and/or HIV acquisition, and cytokine production was assayed by intracellular cytokine staining. The integrin alpha4beta7 was expressed on 26.0% of cervical CD4(+) T cells, and these cells were more likely to express both the HIV coreceptor CCR5 (p < 0.0001) and the early activation marker CD69 (p < 0.0001) but not CXCR4 (p = 0.34). Cervical Th17 frequencies were enhanced compared with blood (7.02 versus 1.24%; p < 0.0001), and cervical IL-17A(+) CD4(+) T cells preferentially coexpressed alpha4beta7 and CCR5. Expression of IFN-gamma and IL-22 was greater in cervical Th17 cells than in blood Th17 cells. In keeping with the hypothesis that these cells are preferential HIV targets, gp120 preferentially bound CCR5(+) cervical T cells, and cervical Th17 cells were almost completely depleted in HIV(+) FSWs compared with HIV(-) FSWs. In summary, a subset of Th17 CD4(+) T cells in the cervical mucosa coexpresses multiple HIV susceptibility markers; their dramatic depletion after HIV infection suggests that these may serve as key target cells during HIV transmission. PMID- 22048766 TI - Eosinophils regulate dendritic cells and Th2 pulmonary immune responses following allergen provocation. AB - Reports have recently suggested that eosinophils have the potential to modulate allergen-dependent pulmonary immune responses. The studies presented expand these reports demonstrating in the mouse that eosinophils are required for the allergen dependent Th2 pulmonary immune responses mediated by dendritic cells (DCs) and T lymphocytes. Specifically, the recruitment of peripheral eosinophils to the pulmonary lymphatic compartment(s) was required for the accumulation of myeloid DCs in draining lymph nodes and, in turn, Ag-specific T effector cell production. These effects on DCs and Ag-specific T cells did not require MHC class II expression on eosinophils, suggesting that these granulocytes have an accessory role as opposed to direct T cell stimulation. The data also showed that eosinophils uniquely suppress the DC-mediated production of Th17 and, to smaller degree, Th1 responses. The cumulative effect of these eosinophil-dependent immune mechanisms is to promote the Th2 polarization characteristic of the pulmonary microenvironment after allergen challenge. PMID- 22048767 TI - Lineage(-)Sca1+c-Kit(-)CD25+ cells are IL-33-responsive type 2 innate cells in the mouse bone marrow. AB - IL-33 promotes type 2 immune responses, both protective and pathogenic. Recently, targets of IL-33, including several newly discovered type 2 innate cells, have been characterized in the periphery. In this study, we report that bone marrow cells from wild-type C57BL/6 mice responded with IL-5 and IL-13 production when cultured with IL-33. IL-33 cultures of bone marrow cells from Rag1 KO and Kit(W sh/W-sh) mice also responded similarly; hence, eliminating the possible contributions of T, B, and mast cells. Rather, intracellular staining revealed that the IL-5- and IL-13-positive cells display a marker profile consistent with the Lineage(-)Sca-1(+)c-Kit(-)CD25(+) (LSK(-)CD25(+)) cells, a bone marrow cell population of previously unknown function. Freshly isolated LSK(-)CD25(+) cells uniformly express ST2, the IL-33 receptor. In addition, culture of sorted LSK( )CD25(+) cells showed that they indeed produce IL-5 and IL-13 when cultured with IL-33 plus IL-2 and IL-33 plus IL-7. Furthermore, i.p. injections of IL-33 or IL 25 into mice induced LSK(-)CD25(+) cells to expand, in both size and frequency, and to upregulate ST2 and alpha(4)beta(7) integrin, a mucosal homing marker. Thus, we identify the enigmatic bone marrow LSK(-)CD25(+) cells as IL-33 responsive, both in vitro and in vivo, with attributes similar to other type 2 innate cells described in peripheral tissues. PMID- 22048768 TI - Pilot clinical trial of type 1 dendritic cells loaded with autologous tumor lysates combined with GM-CSF, pegylated IFN, and cyclophosphamide for metastatic cancer patients. AB - Twenty-four patients with metastatic cancer received two cycles of four daily immunizations with monocyte-derived dendritic cells (DC). DC were incubated with preheated autologous tumor lysate and subsequently with IFN-alpha, TNF-alpha, and polyinosinic:polycytidylic acid to attain type 1 maturation. One DC dose was delivered intranodally, under ultrasound control, and the rest intradermally in the opposite thigh. Cyclophosphamide (day -7), GM-CSF (days 1-4), and pegIFN alpha-2a (days 1 and 8) completed each treatment cycle. Pretreatment with cyclophosphamide decreased regulatory T cells to levels observed in healthy subjects both in terms of percentage and in absolute counts in peripheral blood. Treatment induced sustained elevations of IL-12 in serum that correlated with the output of IL-12p70 from cultured DC from each individual. NK activity in peripheral blood was increased and also correlated with the serum concentration of IL-12p70 in each patient. Circulating endothelial cells decreased in 17 of 18 patients, and circulating tumor cells markedly dropped in 6 of 19 cases. IFN gamma-ELISPOT responses to DC plus tumor lysate were observed in 4 of 11 evaluated cases. Tracing DC migration with [(111)In] scintigraphy showed that intranodal injections reached deeper lymphatic chains in 61% of patients, whereas with intradermal injections a small fraction of injected DC was almost constantly shown to reach draining inguinal lymph nodes. Five patients experienced disease stabilization, but no objective responses were documented. This combinatorial immunotherapy strategy is safe and feasible, and its immunobiological effects suggest potential activity in patients with minimal residual disease. A randomized trial exploring this hypothesis is currently ongoing. PMID- 22048769 TI - Cannabinoid receptor 2 is critical for the homing and retention of marginal zone B lineage cells and for efficient T-independent immune responses. AB - The endocannabinoid system has emerged as an important regulator of immune responses, with the cannabinoid receptor 2 (CB2) and its principle ligand 2 archidonoylglycerol playing a major role. How CB2 regulates B cell functions is not clear, even though they express the highest levels of CB2 among immune cell subsets. In this study, we show that CB2-deficient mice have a significant reduction in the absolute number of marginal zone (MZ) B cells and their immediate precursor, transitional-2 MZ precursor. The loss of MZ lineage cells in CB2(-/-) mice was shown to be B cell intrinsic using bone marrow chimeras and was not due to a developmental or functional defect as determined by B cell phenotype, proliferation, and Ig production. Furthermore, CB2(-/-) B cells were similar to wild type in their apoptosis, cell turnover, and BCR and Notch-2 signaling. We then demonstrated that CB2(-/-) MZ lineage B cells were less efficient at homing to the MZ and that their subsequent retention was also regulated by CB2. CB2(-/-) mice immunized with T-independent Ags produced significantly less Ag-specific IgM. This study demonstrates that CB2 positively regulates T-independent immune responses by controlling the localization and positioning of MZ lineage cells to the MZ. PMID- 22048770 TI - Virally-induced upregulation of heparan sulfate on B cells via the action of type I IFN. AB - Cell surface heparan sulfate (HS) is an important coreceptor for many cytokines, chemokines, and growth factors. In this study, we report that splenic murine B cells express very little HS and that upon infection with either gammaherpesvirus (murine gammaherpesvirus 68) or betaherpesvirus (murine cytomegalovirus), HS is rapidly upregulated at the surface of B cells. HS upregulation was not observed in mice deficient for the type I IFN (IFN-I) receptor. Additionally, treatment of wild-type mice with the IFN-I inducer polyinosine polycytidylic acid triggered HS expression at the B cell surface. Similarly, incubation of purified splenic B cells with IFN-I, TLR ligands, or BCR stimulators ex vivo resulted in a drastic increase in HS surface expression. We found that IFN-I induced an increase in the surface expression of HS-modified syndecan 4 as well as that of an unidentified heparan sulfate proteoglycan. Finally, IFN-I treatment increased B cell responsiveness to APRIL, a cytokine involved in B cell survival and T cell independent B cell responses. Enzymatic removal of HS from IFN-I-treated B cells inhibited APRIL. Altogether, our results indicate that upon herpesvirus infection in mice, HS is rapidly upregulated at the surface of B cells due to the action of IFN-I, potentially increasing B cell responsiveness to cytokines. Induction of HS expression at the B cell surface by stimulators of the innate immune response likely plays a key role in the development of a robust immune response. PMID- 22048771 TI - SAP-mediated inhibition of diacylglycerol kinase alpha regulates TCR-induced diacylglycerol signaling. AB - Diacylglycerol kinases (DGKs) metabolize diacylglycerol to phosphatidic acid. In T lymphocytes, DGKalpha acts as a negative regulator of TCR signaling by decreasing diacylglycerol levels and inducing anergy. In this study, we show that upon costimulation of the TCR with CD28 or signaling lymphocyte activation molecule (SLAM), DGKalpha, but not DGKzeta, exits from the nucleus and undergoes rapid negative regulation of its enzymatic activity. Inhibition of DGKalpha is dependent on the expression of SAP, an adaptor protein mutated in X-linked lymphoproliferative disease, which is essential for SLAM-mediated signaling and contributes to TCR/CD28-induced signaling and T cell activation. Accordingly, overexpression of SAP is sufficient to inhibit DGKalpha, whereas SAP mutants unable to bind either phospho-tyrosine residues or SH3 domain are ineffective. Moreover, phospholipase C activity and calcium, but not Src-family tyrosine kinases, are also required for negative regulation of DGKalpha. Finally, inhibition of DGKalpha in SAP-deficient cells partially rescues defective TCR/CD28 signaling, including Ras and ERK1/2 activation, protein kinase C membrane recruitment, induction of NF-AT transcriptional activity, and IL-2 production. Thus SAP-mediated inhibition of DGKalpha sustains diacylglycerol signaling, thereby regulating T cell activation, and it may represent a novel pharmacological strategy for X-linked lymphoproliferative disease treatment. PMID- 22048772 TI - Antimicrobial peptides inhibit polyinosinic-polycytidylic acid-induced immune responses. AB - Viral proteins and nucleic acids stimulate TLRs to elicit production of cytokines, chemokines, and IFNs. Because of their immunostimulatory activity, several TLR agonists are being developed as vaccine adjuvants and cancer immunotherapeutics. However, TLR signaling is modified by disease state, which could enhance or impair therapeutic efficacy. For example, in the skin of psoriasis patients, the human cationic antimicrobial peptide LL37 is highly expressed and binds to host DNA. Association with LL37 enhances DNA uptake into intracellular compartments, where it stimulates TLR9-dependent overproduction of IFNs. Polyinosinic-polycytidylic acid (poly(I:C)), an analog of viral dsRNA, is recognized by TLR3 and is currently in preclinical trials as an inducer of type I IFN. If LL37 similarly enhanced IFN production, use of poly(I:C) might be contraindicated in certain conditions where LL37 is elevated. In this study, we show that TLR3 signaling was not enhanced, but was dramatically inhibited, by LL37 or mouse cathelicidin-related antimicrobial peptide in macrophages, microglial cells, and dendritic cells. Inhibition correlated with formation of a strong complex between antimicrobial peptides and poly(I:C), which partially inhibited poly(I:C) binding to TLR3. Therefore, after injury or during existing acute or chronic inflammation, when LL37 levels are elevated, the therapeutic activity of poly(I:C) will be compromised. Our findings highlight the importance of using caution when therapeutically delivering nucleic acids as immunomodulators. PMID- 22048773 TI - Peptidoglycan recognition protein Pglyrp2 protects mice from psoriasis-like skin inflammation by promoting regulatory T cells and limiting Th17 responses. AB - Skin protects the body from the environment and is an important component of the innate and adaptive immune systems. Psoriasis is a frequent inflammatory skin disease of unknown cause determined by multigenic predisposition, environmental factors, and aberrant immune response. Peptidoglycan recognition proteins (Pglyrps) are expressed in the skin, and we report in this article that they modulate sensitivity in an experimentally induced mouse model of psoriasis. We demonstrate that Pglyrp2(-/-) mice (but not Pglyrp3(-/-) and Pglyrp4(-/-) mice) are more sensitive to the development of 12-O-tetradecanoylphorbol 13-acetate induced psoriasis-like inflammation, whereas Pglyrp1(-/-) mice are less sensitive. The mechanism underlying this increased sensitivity of Pglyrp2(-/-) mice to 12-O-tetradecanoylphorbol 13-acetate-induced psoriasis-like inflammation is reduced recruitment of regulatory T cells to the skin and enhanced production and activation of Th17 cells in the skin in Pglyrp2(-/-) mice, which results in more severe inflammation and keratinocyte proliferation. Thus, in wild type mice, Pglyrp2 limits overactivation of Th17 cells by promoting accumulation of regulatory T cells at the site of inflammation, which protects the skin from the exaggerated inflammatory response. PMID- 22048774 TI - A critical role for macrophages in promotion of urethane-induced lung carcinogenesis. AB - Macrophages have established roles in tumor growth and metastasis, but information about their role in lung tumor promotion is limited. To assess the role of macrophages in lung tumorigenesis, we developed a method of minimally invasive, long-term macrophage depletion by repetitive intratracheal instillation of liposomal clodronate. Compared with controls treated with repetitive doses of PBS-containing liposomes, long-term macrophage depletion resulted in a marked reduction in tumor number and size at 4 mo after a single i.p. injection of the carcinogen urethane. After urethane treatment, lung macrophages developed increased M1 macrophage marker expression during the first 2-3 wk, followed by increased M2 marker expression by week 6. Using a strategy to reduce alveolar macrophages during tumor initiation and early promotion stages (weeks 1-2) or during late promotion and progression stages (weeks 4-16), we found significantly fewer and smaller lung tumors in both groups compared with controls. Late-stage macrophage depletion reduced VEGF expression and impaired vascular growth in tumors. In contrast, early-stage depletion of alveolar macrophages impaired urethane-induced NF-kappaB activation in the lungs and reduced the development of premalignant atypical adenomatous hyperplasia lesions at 6 wk after urethane injection. Together, these studies elucidate an important role for macrophages in lung tumor promotion and indicate that these cells have distinct roles during different stages of lung carcinogenesis. PMID- 22048775 TI - IL-1beta and TGF-beta act antagonistically in induction and differentially in propagation of human proinflammatory precursor CD4+ T cells. AB - Cytokines are critical messengers that control the differentiation of Th cells. To evaluate their impact on the fate of human naive CD4(+) T cells from cord and adult blood, early T cell differentiation was monitored after T cell activation in the presence of pro- and anti-inflammatory cytokines. Interestingly, the analysis of Th cell lineage-specific molecules revealed that IL-1beta on its own mediates differentiation of Th cells that secrete a wide range of proinflammatory cytokines and stably express CD69, STAT1, IFN-gamma, and IL-17. Notably, our data suggest that IL-1beta induces Th17 cells independent of RORC upregulation. In contrast, TGF-beta that triggers RORC prevents Th17 cell development. This suppressive function of TGF-beta is characterized by inhibition of STAT1, STAT3, and CD69. However, after repeated anti-CD3 and anti-CD28 stimulation, we observe that TGF-beta provokes an increase in Th17 cells that presumably relies on reactivation of a default pathway by preferential inhibition of IFN-gamma. Hence, our data extend the view that the principal cytokines for determining Th cell fate are IL-12 for the Th1 lineage, IL-4 for the Th2 lineage, and TGF-beta in conjunction with IL-6 for the Th17 lineage. We propose that IL-1beta induces a general proinflammatory Th cell precursor that, in the presence of the lineage specifying cytokines, further differentiates into one of the specific Th cell subpopulations. PMID- 22048776 TI - Fabrication of cell container arrays with overlaid surface topographies. AB - This paper presents cell culture substrates in the form of microcontainer arrays with overlaid surface topographies, and a technology for their fabrication. The new fabrication technology is based on microscale thermoforming of thin polymer films whose surfaces are topographically prepatterned on a micro- or nanoscale. For microthermoforming, we apply a new process on the basis of temporary back moulding of polymer films and use the novel concept of a perforated-sheet-like mould. Thermal micro- or nanoimprinting is applied for prepatterning. The novel cell container arrays are fabricated from polylactic acid (PLA) films. The thin walled microcontainer structures have the shape of a spherical calotte merging into a hexagonal shape at their upper circumferential edges. In the arrays, the cell containers are arranged densely packed in honeycomb fashion. The inner surfaces of the highly curved container walls are provided with various topographical micro- and nanopatterns. For a first validation of the microcontainer arrays as in vitro cell culture substrates, C2C12 mouse premyoblasts are cultured in containers with microgrooved surfaces and shown to align along the grooves in the three-dimensional film substrates. In future stem cell-biological and tissue engineering applications, microcontainers fabricated using the proposed technology may act as geometrically defined artificial microenvironments or niches. PMID- 22048777 TI - A chelating-bond breaking and re-linking technique for rapid re-immobilization of immune micro-sensors. AB - With high sensitivity and specificity to antigen, immune micro-sensors can be used in rapid detection of pathogenic microbial. This study proposes and develops a method for rapidly regeneration of antibody on a resonant micro-cantilever sensor. A nitrilotriacetic acid (NTA) derivative is synthesized with cystine and bromoacetic acid, then added with 2-mercaptoethanol to prepare a mixed self assembled monolayer (SAM) on Au (111) surface of the cantilever. Ni2+ ions are thereafter chelated on the mixed SAM to form a breakable and re-linkable chelating-bond layer. Repeatable cycles of antibody immobilization and erasing are experimentally validated with a detectable marker of synthesized biotinylated poly peptides harboring six histidine residues (named as His-Bio). Two distinguished pathogenic microbial, Escherichia. coli O157:H7 and Bacillus Anthracis, are detected with the rapidly regenerated sensor. The E. coli O157:H7 sensor exhibits a three-time repeated detection to the 103 CFU/ml concentration microbial. Then, an E. coli O157:H7 sensor is eluted with Tris-HCl (20 mM Tris, 150 mM NaCl, 0.1% Tween 20, pH = 3.0) and rapidly reconstructed into a B. Anthracis sensor by changing the re-immobilized antibody. The cantilever sensor no longer responses to E. coli O157:H7 even in a high concentration of 107 CFU/ml. In contrast, the sensor is experimentally confirmed being resoluble to low concentration B. Anthracis at 103 spores/ml level. The proposed fast regeneration method is promising in repeatedly or multi-target detection applications of micro/nano immune-sensors, e.g. the resonant micro-cantilevers. PMID- 22048778 TI - Community duplicate diet methodology: a new tool for estimating dietary exposures to pesticides. AB - An observational field study was conducted to assess the feasibility of a community duplicate diet collection method; a dietary monitoring tool that is population-based. The purpose was to establish an alternative procedure to duplicate diet sampling that would be more efficient for a large, defined population, e.g., in the National Children's Study (NCS). Questionnaire data and food samples were collected in a residence so as not to lose the important component of storage, preparation, and handling in a contaminated microenvironment. The participants included nine Hispanic women of child bearing age living in Apopka, FL, USA. Foods highly consumed by Hispanic women were identified based on national food frequency questionnaires and prioritized by permethrin residue concentrations as measured for the Pesticide Data Program. Participants filled out questionnaires to determine if highly consumed foods were commonly eaten by them and to assess the collection protocol for the food samples. Measureable levels of permethrin were found in 54% of the samples. Questionnaire responses indicated that the collection of the community duplicate diet was feasible for a defined population. PMID- 22048779 TI - Enhanced UHF RFID tags for drug tracing. AB - Radio Frequency Identification (RFID) technology is playing a crucial role for item-level tracing systems in healthcare scenarios. The pharmaceutical supply chain is a fascinating application context, where RFID can guarantee transparency in the drug flow, supporting both suppliers and consumers against the growing counterfeiting problem. In such a context, the choice of the most adequate RFID tag, in terms of shape, frequency, size and reading range, is crucial. The potential presence of items containing materials hostile to the electromagnetic propagation exasperates the problem. In addition, the peculiarities of the different RFID-based checkpoints make even more stringent the requirements for the tag. In this work, the performance of several commercial UHF RFID tags in each step of the pharmaceutical supply chain has been evaluated, confirming the expected criticality. On such basis, a guideline for the electromagnetic design of new high-performance tags capable to overcome such criticalities has been defined. Finally, driven by such guidelines, a new enhanced tag has been designed, realized and tested. Due to patent pending issues, the antenna shape is not shown. Nevertheless, the optimal obtained results do not lose their validity. Indeed, on the one hand they demonstrate that high performance item level tracing systems can actually be implemented also in critical operating conditions. On the other hand, they encourage the tag designer to follow the identified guidelines so to realize enhanced UHF tags. PMID- 22048780 TI - Security risks associated with radio frequency identification in medical environments. AB - Radio frequency identification (RFID) is a form of wireless communication that is used to identify assets and people. RFID has significant benefits to the medical environment. However, serious security threats are present in RFID systems that must be addressed in a medical environment. Of particular interest are threats to patient privacy and safety based on interception of messages, interruption of communication, modification of data, and fabrication of messages and devices. This paper presents an overview of these security threats present in RFID systems in a medical environment and provides guidance on potential solutions to these threats. This paper provides a roadmap for researchers and implementers to address the security issues facing RFID in the medical space. PMID- 22048781 TI - A secure integrated medical information system. AB - The rapid rise and development of the internet has made digitization of our everyday life common. E-medicine, including electronic prescription records, electronic prescriptions, diagnosis information systems, and others are now being regarded as future trends. As development on the structure and format of electronic patient records and prescriptions matures, the implementation of a comprehensive medical information system is imperative, one which is constructed from integrating the various electronic information systems that is being developed. It is important to allow the implementation of such a system applicable to the present medical environment, which facilitates the integration of electronic patient record from all levels of medical centers and clinics, secures the transmission of these integrated patient records between them, enables the combined use of electronic prescriptions with patients' medications, and permits anonymous or confidential transmission of patients' private data. To put the ideas into practice, in this study, we would like to propose an Integrated Medical Information System. PMID- 22048782 TI - Dual function seal: visualized digital signature for electronic medical record systems. AB - Digital signature is an important cryptography technology to be used to provide integrity and non-repudiation in electronic medical record systems (EMRS) and it is required by law. However, digital signatures normally appear in forms unrecognizable to medical staff, this may reduce the trust from medical staff that is used to the handwritten signatures or seals. Therefore, in this paper we propose a dual function seal to extend user trust from a traditional seal to a digital signature. The proposed dual function seal is a prototype that combines the traditional seal and digital seal. With this prototype, medical personnel are not just can put a seal on paper but also generate a visualized digital signature for electronic medical records. Medical Personnel can then look at the visualized digital signature and directly know which medical personnel generated it, just like with a traditional seal. Discrete wavelet transform (DWT) is used as an image processing method to generate a visualized digital signature, and the peak signal to noise ratio (PSNR) is calculated to verify that distortions of all converted images are beyond human recognition, and the results of our converted images are from 70 dB to 80 dB. The signature recoverability is also tested in this proposed paper to ensure that the visualized digital signature is verifiable. A simulated EMRS is implemented to show how the visualized digital signature can be integrity into EMRS. PMID- 22048783 TI - Uterine artery embolization versus surgery for symptomatic uterine fibroids: a randomized controlled trial and a meta-analysis of the literature. AB - PURPOSE: The aim of our study was to compare the efficacy and safety of uterine artery embolization (UAE) for symptomatic uterine fibroids with surgery. METHODS: Both a randomized, controlled trial and meta-analysis of existing studies were performed. RESULTS: Patients were randomly assigned in a 1:1 ratio to undergo either UAE or surgery with 63 patients undergoing UAE and 64 undergoing surgery. A meta-analysis of existing studies was also performed.There were significant improvements in UAE groups in most components of quality of life assessment at 6 months. Besides, the UAE group had a shorter hospital stay (P < 0.01) and a shorter recovery time (P < 0.01) compared with the surgical group. During the follow-up, there were no difference in complications incidence (58 vs. 65%, P > 0.05), but the UAE group had less major complications (0 vs. 6%, P < 0.05). Meta analysis of existing studies including those from the current study, further suggested that UAE group had a shorter hospital stay, a shorter recovery time and less major complications than the surgical group. CONCLUSIONS: Compared with surgery, UAE has a shorter hospital stay, a shorter recovery time, and less major complications. More studies in the future need to done to evaluate its long-term effects and impact on fertility. PMID- 22048784 TI - Uterine perforation with omentum incarceration after dilatation and evacuation/curettage: magnetic resonance imaging findings. AB - INTRODUCTION: Cervical dilatation and/or uterine evacuation and curettage (D/E&C) is the most commonly performed and safest gynecological procedure. Although procedure-related uterine perforation is rare, this condition may require surgical intervention. Ultrasound examination and computed tomography are useful for diagnosing such perforations with incarceration of an intra-abdominal organ. However, the use of magnetic resonance imaging (MRI) for detecting postabortal uterine damage has seldom been discussed in the literature. CASE REPORT: A 31 year-old woman was referred to our department for lower abdominal pain and a small amount of vaginal bleeding 28 days after D/E&C for a missed abortion. Transvaginal ultrasound examination showed the presence of a hyperechogenic structure in the anterior wall of the uterine body, which was verified to be fatty tissue by MRI, particularly on the fat-suppressed T1-weighted images. An emergency laparotomy showed a uterine perforation with omentum incarceration. After dissecting the omental loop, the uterine perforation site was incised, and the involved omental tissue was debrided appropriately. DISCUSSION: To our knowledge, this is the first report wherein MRI was used for the detection of incarcerated omental fat within the uterus. Delayed presentation of uterine perforation may be observed 1 month or more after D/E&C, although such a finding is extremely rare. Therefore, postabortal follow-up bimanual vaginal examination using transvaginal ultrasonography is recommended. The current study indicates the usefulness of MRI when myometrial perforation with or without incarceration of an extrauterine organ is suspected. PMID- 22048785 TI - Morbidity in elderly women undergoing gynaecological pelvic floor surgery. AB - PURPOSE: We investigated the morbidity in elderly patients undergoing surgery due to pelvic organ prolapse. METHODS: Perioperative data of 113 patients aged at least 50 years who underwent gynaecological prolapse surgery between 2005 and 2011 were analyzed retrospectively. Forty-eight women were older than 70 years and matched our inclusion criteria. Sixty-five patients aged 50-69 years undergoing similar surgical procedures during the same period of time formed the control group. Operating time, duration of hospital stay, intra- and postoperative complications, comorbidity, and body mass index were evaluated. RESULTS: There were no significant differences between study and control collective regarding operating time, duration of hospital stay, intra- and postoperative complications, and body mass index although a significant difference could be notified between the pre-existing comorbidity. CONCLUSION: Surgery due to a pelvic organ prolapse in patients aged more than 70 years is a feasible and save treatment to improve quality of life in elderly patients. PMID- 22048786 TI - Expanding the 'enemy-free space' for oribatid mites: evidence for chemical defense of juvenile Archegozetes longisetosus against the rove beetle Stenus juno. AB - Adult oribatid mites are thought to live functionally in 'enemy-free space' due to numerous morphological and chemical defensive strategies. Most juvenile oribatid mites, however, lack hardened cuticles and are thus thought to be under stronger predation pressure. On the other hand, the majority of oribatids have exocrine oil glands in all developmental stages, possibly rendering chemical defense the crucial survival strategy in juvenile Oribatida. We manipulated tritonymphs of the model oribatid mite Archegozetes longisetosus to completely discharge their oil glands and offered these chemically disarmed specimens to the polyphagous rove beetle Stenus juno. Disarmed specimens were easily consumed. By contrast, specimens with filled oil glands were significantly protected, being rejected by the beetles. This is the first direct evidence that oil gland secretions provide soft-bodied juvenile oribatids with chemical protection against large arthropod predators. PMID- 22048787 TI - MicroRNA-143 expression in dorsal root ganglion neurons. AB - The unpleasant sensory and emotional experience of pain is initiated by excitation of primary afferent nociceptive neurons. Nerve damage or inflammation induces changes in nociceptive DRG neurons which contribute to both peripheral and central sensitization of pain-sensitive pathways. Recently, blockade of microRNA synthesis has been found to modulate the response of nociceptive neurons to inflammatory stimuli. However, little is known about the contributions of individual miRNAs to painful conditions. We compared miRNA expression in mouse sensory neurons and focussed on the localisation and control of miR-143. Using miRNA-arrays we compared the microRNA expression profile of intact lumbar DRG with one-day-old DRG cultures and found that nine miRNAs including miR-143 showed lower expression levels in cultures. Subsequent RT-qPCR confirmed array data and in-situ hybridisation localised miR-143 in the cytosol of sensory DRG neurons in situ and in vitro. Analysis of microbead-enriched neuron cultures showed significantly higher expression levels of miR-143 in isolectin B4 (I-B4) binding sensory neurons compared with neurons in the I-B4 negative flow-through fraction. In animal models of peripheral inflammation (injection of Complete Freund's Adjuvant, CFA) and nerve damage (transection of the sciatic nerve), we found that expression levels of miR-143 were significantly lower in DRGs ipsilateral to CFA injection or after nerve damage. Taken together, our data demonstrate for the first time miR-143 expression in nociceptive neurons. Since expression levels of miR-143 were higher in I-B4 positive neurons and declined in response to inflammation but not axotomy, miR-143 could selectively contribute to mRNA regulation in specific populations of nociceptors. PMID- 22048788 TI - Physical therapist practice and the role of diagnostic imaging. AB - SYNOPSIS: For healthcare providers involved in the management of patients with musculoskeletal disorders, the ability to order diagnostic imaging is a beneficial adjunct to screening for medical referral and differential diagnosis. A trial of conservative treatment, such as physical therapy, is often recommended prior to the use of imaging in many treatment guidelines for the management of musculoskeletal conditions. In the United States, physical therapists are becoming more autonomous and can practice some degree of direct access in 48 states and Washington, DC. Referral for imaging privileges could increase the effectiveness and efficiency of healthcare delivery, particularly in combination with direct access management. This clinical commentary proposes that, given the American Physical Therapy Association's goal to have physical therapists as primary care musculoskeletal specialists of choice, it would be beneficial for physical therapists to have imaging privileges in their practice. The purpose of this commentary is 3-fold: (1) to make a case for the use of imaging privileges by physical therapists, using a historical perspective; (2) to discuss the barriers preventing physical therapists from having this privilege; and (3) to offer suggestions on strategies and guidelines to facilitate the appropriate inclusion of referral for imaging privileges in physical therapist practice. J Orthop Sports Phys Ther 2011;41(11):829-837. doi:10.2519/jospt.2011.3556. PMID- 22048789 TI - Human herpesvirus 6 in biopsies from patients with gastrointestinal symptoms after allogeneic stem cell transplantation. AB - Gastrointestinal complications are frequent after allogeneic stem cell transplantation (allo-SCT). Main differential diagnoses are graft-versus-host disease (GvHD) and viral infections. In this retrospective analysis, we included 50 patients with severe vomiting or diarrhea in the first year after allo-SCT. One hundred two biopsies obtained by colonoscopy or endoscopy of the upper gastrointestinal tract were analysed by conventional histology for signs of GvHD and by qualitative polymerase chain reaction (PCR) for viral DNA of human herpesvirus 6 (HHV-6) and other virus of the herpes family. DNA of HHV-6 was detected in 38 of 75 initial samples (51%) and in 19 of 27 follow-up biopsies (70%). In the initial samples (n = 75), HHV-6 DNA was detected in 20/37 (54%) biopsies in the presence of GvHD compared to 18/38 (47%) biopsies without signs of GvHD. At the time of the first endoscopic investigation, most patients received antiviral prophylaxis with aciclovir. None of the follow-up biopsies was HHV-6 DNA negative after antiviral treatment with aciclovir, foscarnet or ganciclovir. By univariate analysis, no risk factor for HHV-6 detection could be demonstrated. In this cohort of patients with severe gastrointestinal complications, there was no significant difference in the overall survival between patients with or without HHV-6 DNA detection in the gastrointestinal tract. In summary, the detection of HHV-6 DNA had no impact on overall survival. Moreover, antiviral therapy against HHV-6 was without effect. Thus, positive PCR results in GI tract samples do not necessarily reflect reactivation of HHV-6. Further studies are needed to define the significance of HHV-6 for GI tract symptoms after allo-SCT. PMID- 22048790 TI - Good adherence to imatinib therapy among patients with chronic myeloid leukemia- a single-center observational study. AB - Previous studies have suggested that adherence to imatinib therapy can be an obstacle among patients with chronic myeloid leukemia (CML). We studied adherence to imatinib therapy among CML patients treated at the Sahlgrenska University Hospital. We identified all CML patients that were alive at the 1st of January 2010 (n = 70). Nineteen patients were excluded due to a history of allogenic hematopoietic stem cell transplantation, and nine were excluded due to treatment with other tyrosine kinase inhibitors. Thirty-eight out of 42 patients (90%) treated with imatinib accepted inclusion in the study. The patients were interviewed in a structured way, and adherence was evaluated in a standardized way using the nine-item Morisky Medication Adherence Scale that ranges from 1 to 13. A Morisky score <=10 indicates nonadherence and >=11 indicates adherence. In addition, predefined follow-up questions were asked to identify factors known to influence adherence to therapy. In contrast to previous studies, our patients showed good adherence to imatinib therapy with a mean Morisky score of 12.3 out of 13 (range, 9-13). The interviews revealed factors known to predict adherence to therapy, namely being well informed and having frequent contact with a single hematologist. Furthermore, the patients had easy access to the treating clinic and felt that they took part in decisions concerning their disease and treatment. We show that adherence to imatinib can be very good in CML patients, and we suggest that simple measures such as increased patient information and continuity of care will increase adherence in patients with CML. PMID- 22048792 TI - Observational study of sleep-related disorders in Italian patients with Parkinson's disease: usefulness of the Italian version of Parkinson's disease sleep scale. AB - Sleep disturbances are common in patients with Parkinson's disease (PD). We aimed to evaluate prevalence and severity of nighttime sleep disturbances in Italian PD patients and to validate the Italian version of the Parkinson's disease sleep scale. A total of 221 PD patients and 57 healthy controls participated in a cross sectional study with retest. PDSS, Epworth Sleepiness Scale (ESS), Hamilton Depression Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr staging were applied. PDSS total and individual items scores from patients were significantly lower than those in controls. Internal consistency of PDSS scale was satisfactory and intraclass correlation coefficient for test retest reliability was 0.96 for total PDSS score. A significant negative correlation was found between total PDSS and ESS scores, and between total PDSS and HDRS scores. PDSS scores were also related to UPDRS sections II, III and IV, and H&Y stage. PDSS and ESS scores were not related to levodopa equivalent dose. Daytime sleepiness, depressive symptoms and disease severity correlate with sleep disturbances in Italian PD patients. The PDSS is a valid and reliable tool to evaluate sleep disturbances in Italian patients. PMID- 22048791 TI - Frontal assessment battery scores and non-motor symptoms in parkinsonian disorders. AB - Using data from the PRIAMO study, we investigated non-motor symptoms (NMS) versus frontal lobe dysfunction in patients with idiopathic Parkinson disease (PD); 808 patients with PD and 118 with atypical parkinsonisms (AP) were consecutively enrolled at 55 Centers in Italy. Twelve categories of NMS were investigated. Cognitive impairment was defined as a Mini-Mental Status Evaluation score <= 23.8 and frontal lobe dysfunction as a Frontal Assessment Battery (FAB) score <= 3.48. Multivariable logistic regression was used to identify predictor of frontal lobe dysfunction in 524 PD patients, and a generalized linear model was used for each of the six FAB items. Not only the total FAB scores but also the single FAB items were lower in AP versus PD (p <= 0.005). Age (OR = 1.05), cognitive impairment (OR = 9.54), lack of cardiovascular symptoms (OR = 3.25), attention or memory problems (OR = 0.59) and treatment with L: -DOPA (OR = 5.58) were predictors of frontal lobe dysfunction. MMSE was negatively associated with all FAB items (beta <= -0.16) and age with all FAB items but prehension behavior (beta <= -0.01). Previous use of L: -DOPA was negatively associated with verbal fluency (beta = 0.32) possibly acting as surrogate marker of disease duration. Cognitive impairment is a predictor of frontal lobe dysfunction. Among NMS, lack of attention or memory problems were negatively associated with frontal impairment. Further studies are nonetheless needed to better identify the predictors of frontal impairment in PD patients. PMID- 22048793 TI - A pilot study of the effects of non-invasive mechanical ventilation on the prognosis of ischemic cerebrovascular events in patients with obstructive sleep apnea syndrome. AB - Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for ischemic cerebrovascular diseases, and results in worse prognosis and higher mortality. We aimed to investigate the effects of early treatment of OSAS on the prognosis of ischemic stroke. We prospectively evaluated patients with acute supratentorial ischemic stroke and OSAS on admission (acute stage), at second week (subacute stage) and at second month (chronic stage); 11 (73.3%) out of 15 patients put on the non-invasive mechanical ventilation treatment within 48 h of stroke constituted the treatment group, and 13 patients constituted the control group. Patients with OSAS treatment showed significantly better prognosis and better functioning in activities of daily living in both subacute and chronic stages. The rate of shrinkage of the ischemic lesion was higher in the treatment group, though not significant. The early and effective treatment of OSAS provides a better clinical prognosis in ischemic stroke. The beneficial effects on radiological parameters need to be further studied. PMID- 22048794 TI - Serum caspase-9 levels are increased in patients with amyotrophic lateral sclerosis. AB - It is known that apoptosis may play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Moreover, caspase-9 is implicated in the apoptosis pathway. The aim of the study was to investigate caspase-9 levels in serum of patients with ALS. The study involved 30 patients with ALS and 30 patients from the control group. The serum caspase-9 levels were measured using the enzyme linked immunosorbent method. The study showed that caspase-9 levels are significantly increased in serum of the patients with ALS comparing to the control group (p < 0.05). There was a significant correlation of serum caspase-9 levels with severity of clinical state of ALS patients and duration of the disease (p < 0.05). The results indicate that caspase-9 may be implicated in pathomechanism of neurodegeneration in ALS. PMID- 22048795 TI - Non-discussed poster presentations of the Joint Meeting of the International Continence Society and the International Urogynecological Association. August 23 27, 2010. Toronto, Canada. PMID- 22048796 TI - Bleeding risk assessment and management in atrial fibrillation patients. Executive Summary of a Position Document from the European Heart Rhythm Association [EHRA], endorsed by the European Society of Cardiology [ESC] Working Group on Thrombosis. AB - In this executive summary of a Consensus Document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in atrial fibrillation (AF) patients. The main aim of the document was to summarise 'best practice' in dealing with bleeding risk in AF patients when approaching antithrombotic therapy, by addressing the epidemiology and size of the problem, and review established bleeding risk factors. We also summarise definitions of bleeding in the published literature. Patient values and preferences balancing the risk of bleeding against thromboembolism as well as the prognostic implications of bleeding are reviewed. We also provide an overview of published bleeding risk stratification and bleeding risk schema. Brief discussion of special situations (e.g. periablation, peri-devices such as implantable cardioverter defibrillators [ICD] or pacemakers, presentation with acute coronary syndromes and/or requiring percutanous coronary interventions/stents and bridging therapy) is made, as well as a discussion of the prevention of bleeds and managing bleeding complications. Finally, this document puts forwards consensus statements that may help to define evidence gaps and assist in everyday clinical practice. PMID- 22048797 TI - Cross validation of liquid chromatography-mass spectrometry and lectin array for monitoring glycosylation in fed-batch glycoprotein production. AB - Glycosylation analysis of recombinant glycoproteins is of importance for the biopharmaceutical industry and the production of glycoprotein pharmaceuticals. A commercially available lectin array technology was evaluated for its ability to present a reproducible fingerprint of a recombinant CTLY4-IgG fusion glycoprotein expressed in large scale CHO-cell fermentation. The glycosylation prediction from the array was compared to traditional negative mode capillary LC-MS of released oligosaccharides. It was shown that both methods provide data that allow samples to be distinguished by their glycosylation pattern. This included information about sialylation, the presence of reducing terminal galactose beta1-, terminal N acetylglucosamine beta1-, and antennary distribution. With both methods it was found that a general trend of increased sialylation was associated with an increase of the antenna and reduced amount of terminal galactose beta1-, while N acetylglucosamine beta1- was less affected. LC-MS, but not the lectin array, provided valuable information about the sialic acid isoforms present, including N acetylneuraminic acid, N-glycolylneuraminic acid and their O-acetylated versions. Detected small amounts of high-mannose structures by LC-MS correlated with the detection of the same epitope by the lectin array. PMID- 22048798 TI - Feasibility of fast-track elements in pediatric surgery. AB - BACKGROUND: We recently showed that fast-track pathways could be applied to only one third of patients undergoing routine pediatric surgery. The aim of this study was to investigate various fast-track elements in various procedure types irrespective of the applicability of a whole fast-track pathway. METHODS: Patients undergoing routine surgical procedures from April 2009 to April 2010 were included in the study. 11 groups of procedures were differentiated and quality criteria were established for 8 fast-track elements: analgesia, postoperative nutrition, postoperative mobilization, applicability of minimally invasive surgery when appropriate, hospital stay, postoperative symptoms, complications, and parental evaluation. A fast-track element was considered as successfully applied if used in at least 75% of patients. The hospital stay was compared with data from the German reimbursement system (G-DRG). RESULTS: A total of 203 patients were included. Optimal analgesia was achieved in all procedure types except in oncologic surgery (58%) and ureteral reimplantation (71%). Significant nausea and vomiting occurred only after Kasai operation and "other laparoscopic procedures". Early nutrition was achieved in all procedures except after fundoplication (67%) and Kasai operation (62%). Early postoperative mobilization was not successful after hypospadias repair (40%) and ureteral reimplantation (43%). Minimally invasive techniques could not be applied in 48% of thoracic procedures and in 58% of oncological patients. There were no fast track associated complications. In 4 of 11 procedure types, the mean hospital stay was significantly reduced compared to G-DRG data. There were 4 readmissions (2%). 2 weeks after discharge 94% of interviewed parents evaluated fast-track treatment as excellent. CONCLUSION: Fast-track elements in pediatric surgery increase patient comfort, reduce hospital stay, and achieve a high patient satisfaction. We wish to emphasize the benefits of using fast-track elements irrespective of whether a whole fast-track protocol is applicable. PMID- 22048799 TI - Herlyn-Werner-Wunderlich syndrome: uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis-role of sonographically guided minimally invasive vaginal surgery. PMID- 22048800 TI - Synthesis of 1,2,3-triazole linked galactopyranosides and evaluation of cholera toxin inhibition. AB - We report the synthesis of a series of bivalent 1,2,3-triazole linked galactopyranosides as potential inhibitors of cholera toxin (CT). The inhibitory activity of the bivalent series was examined (ELISA) and the series showed low inhibitory activity (millimolar IC(50)s). Conversely, the monomeric galactotriazole analogues were strong inhibitors of cholera toxin (IC(50) = 71-75 MUM). PMID- 22048801 TI - Metabolomics-lipidomics of eicosanoids and docosanoids generated by phagocytes. AB - Lipid mediators derived from essential fatty acids, such as arachidonic acid, play important roles in physiologic and pathophysiologic processes. Prostaglandins, thromboxane, and leukotrienes are well-known eicosanoids that play critical roles in hemodynamics and inflammation. New families of mediators were recently uncovered that constitute a new genus stimulating resolution of acute inflammation, and are organ-protective. These include the resolvins (E series and D-series), protectins (neuroprotectin D1/protectin D1), and maresins biosynthesized from omega-3 essential fatty acids. Phagocytes play major roles in tissue homeostasis and have a high capacity to produce these mediators, which depend on their tissue and state of activation. It is important to select appropriate methods for identifying target mediators and pathway biomarkers. In this unit, we review state-of-the-art approaches to identify and profile eicosanoid and docosanoid pathways, including specialized pro-resolving mediators resolvins, protectins, and maresins, in relation to their biosynthesis and inactivation by neutrophils and macrophages. PMID- 22048802 TI - Measuring opsonic phagocytosis via Fcgamma receptors and complement receptors on macrophages. AB - Phagocytosis is a cellular process that plays crucial roles in the removal of dead or dying cells, tissue remodeling, and host defense against invading pathogens. Most eukaryotic cells are decorated with glycoproteins containing terminal sialic acids, whose negative charges tend to repel cells, making so called "nonspecific" phagocytosis a relatively inefficient process. Professional phagocytes are so designated because they express two major classes of receptors on their surfaces that are primarily involved in phagocytosis. Paradoxically, these receptors do not recognize microbes directly, but rather endogenous proteins that become tethered to microbes and target them for destruction. These are the Fcgamma receptors that bind to the Fc portion of IgG and the complement receptors (CRs), which bind primarily to cleavage products of the third component of complement, C3. This unit describes assays that are used to measure these two types of macrophage phagocytosis. PMID- 22048803 TI - Experimental autoimmune myasthenia gravis in the mouse. AB - Myasthenia gravis (MG) is a T cell-dependent antibody-mediated autoimmune neuromuscular disease. Antibodies to the nicotinic acetylcholine receptor (AChR) destroy the AChR, thus leading to defective neuromuscular transmission of electrical impulse and to muscle weakness. This unit is a practical guide to the induction and evaluation of experimental autoimmune myasthenia gravis (EAMG) in the mouse, the animal model for MG. Protocols are provided for the extraction and purification of AChR from the electric organs of Torpedo californica, or the electric ray. The purified receptor is used as an immunogen to induce autoimmunity to AChR, thus causing EAMG. The defect in neuromuscular transmission can also be measured quantitatively by electromyography. In addition, EAMG is frequently characterized by the presence of serum antibodies to AChR, which are measured by radioimmunoassay and by a marked antibody-mediated reduction in the number of muscle AChRs. AChR extracted from mouse muscle is used in measuring serum antibody levels and for quantifying muscle AChR content. Another hallmark of the disease is complement and IgG deposits located at the neuromuscular junction, which can be visualized by immunofluorescence techniques. PMID- 22048804 TI - Immortalization of human and rhesus macaque primary antigen-specific T cells by retrovirally transduced telomerase reverse transcriptase. AB - Human and rhesus macaque primary antigen-specific T cells derived from infected or immunized individuals or animals are a valuable material with which to study cellular immune responses against pathogens and tumors. Antigen-specific T cells can be expanded in vitro but have a finite proliferative life span. After a limited period in culture, primary T cells undergo replicative senescence and stop dividing. This restricts their applicability to short-term experiments and complicates their use in adoptive immunotherapy. The proliferative life span of primary human and rhesus macaque T cells can be considerably extended by ectopically expressed human telomerase reverse transcriptase (TERT). Antigen specific T cells transduced with TERT-expressing retroviral vectors can proliferate and expand in culture for long periods of time while maintaining their primary T cell characteristics, including antigen-specific responses. Thus, TERT-immortalized T cells are an important and valuable resource for studying T cell-mediated immune responses and, potentially, for adoptive immunotherapy. PMID- 22048805 TI - Simultaneous powering of forearm pronation and key pinch in tetraplegia using a single muscle-tendon unit. AB - This study clinically assessed the concept that both thumb flexion and forearm pronation can be restored by brachioradialis (BR)-to-flexor pollicis longus (FPL) tendon transfer if the BR is passed dorsal to the radius. Six patients [two women and four men, mean age 32.3 years (SD 4.9, range 23-56)] underwent BR-to-FPL transfer dorsal to the radius and through the interosseous membrane (IOM). Lateral key pinch strength and pronation range of motion (ROM) were measured 1 year after surgery. A group of six patients [two women and four men, mean age 31.2 years (SD 5.0, range 19-52)] who underwent traditional palmar BR-to-FPL was included for comparison. Postoperative active pronation was significantly greater in the dorsal transfer group compared to the palmar group [149 (SD 6) and 75 (SD 3), respectively] and pinch strength was similar in the two groups [1.28 (SD 0.16) kg and 1.20 (SD0.21) kg, respectively]. We conclude that it is feasible to reconstruct lateral key pinch and forearm pronation simultaneously using only the BR motor. PMID- 22048806 TI - Trajectories of preparation for future care among first-degree relatives of Alzheimer's disease patients: an ancillary study of ADAPT. AB - PURPOSE: This study examines the longitudinal patterns of Preparation for Future Care (PFC), defined as Awareness, Avoidance, Gathering Information, Decision Making, and Concrete Plans, in first-degree relatives of people with Alzheimer's disease (AD). DESIGN AND METHODS: Eight time points across 6.5 years from a subsample of adults aged 70 years and older who were participating in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) were analyzed using latent growth modeling. Baseline attitudes toward planning for future care and demographic variables functioned as predictors in the conditional analyses. RESULTS: Awareness, Gathering Information, Decision Making, and Concrete Planning increased across time, but Avoidance did not. Covariates were more often associated with the initial levels of planning behavior than with change across time. Women engaged in more initial Decision Making than men. Education was associated with more initial Gathering Information, Decision Making, and less Avoidance. Favorable attitudes toward planning were more predictive of baseline Awareness, Gathering Information, Avoidance, and less so for Decision Making or Concrete Planning. IMPLICATIONS: Older adults with an elevated risk for AD increase in positive PFC behaviors gradually across time. Demographic characteristics and attitudes predict initial levels of planning, making it possible to identify individuals who might need help progressing to more advanced levels of planning. Future studies are needed to understand rates of change in planning behaviors. PMID- 22048807 TI - Family stigma and caregiver burden in Alzheimer's disease. AB - PURPOSE: The stigma experienced by the family members of an individual with a stigmatized illness is defined by 3 dimensions: caregiver stigma, lay public stigma, and structural stigma. Research in the area of mental illness suggests that caregivers' perception of stigma is associated with increased burden. However, the effect of stigma on caregiver burden among those caring for a relative with Alzheimer's disease (AD) has yet to undergo theoretical and empirical testing. The aim of this study was to examine whether family stigma is a predictor of caregiver burden in the case of Alzheimer's disease. DESIGN AND METHODS: Structured face-to-face interviews were conducted with 185 adult child caregivers (75% female; mean age = 53 years) for persons with Alzheimer's disease. RESULTS: Caregiver stigma variables improved the prediction of caregiver burden by adding an additional 18% to the explained variance over and above the other covariates. The 2 caregiver stigma variables of shame and decreased involvement with caregiving were found to be the major contributing factors. IMPLICATIONS: Our findings show that caregiver stigma increases caregiver burden in the case of Alzheimer's disease. Using this knowledge, psychosocial interventions should target stigmatic beliefs in order to reduce caregiver burden. PMID- 22048808 TI - The coach is in: improving nutritional care in nursing homes. AB - PURPOSE: This article describes and evaluates a long distance coaching course aimed at improving nutritional care in nursing homes (NHs). The course was structured to provide more support than traditional training programs offer. METHODS: In a series of 6 monthly teleconferences led by an expert in NH nutritional care, participating NH staff received step-by-step instructions for implementing an evidence-based nutritional management program. After each session, participants were asked to implement the care step they had just learned. Coaching calls helped facilitate implementation. Staff in 18 NHs in 12 states completed the course. Evaluation data were collected using a resident data form, pre- and post-training quizzes, a participant course evaluation survey, and a supervisor's report. RESULTS: NH staff attended an average of 4.8 teleconferences, with 5 staff members typically attending each teleconference. Average quiz scores increased 30% (p < .0001) from pre- to post-training. A majority of course participants (N = 35) said they would participate in a similar course (82.9%) and would recommend the course (80%). Just under half preferred the coaching course to a more traditional 1- to 2-day conference. Nine of 12 reporting supervisors said their facility planned to continue the new nutritional care program. The 10 NHs that submitted resident data assessed an average of 5 residents using the recommended protocols. IMPLICATIONS: We recommend the coaching course format. Dissemination outcomes may improve if resources currently used for short-duration training activities are used instead on coaching activities that support NHs over extended periods. PMID- 22048809 TI - Older voters and the 2010 U.S. election: implications for 2012 and beyond? AB - PURPOSE: To analyze the extent to which Americans aged 65 and older may have voted as an old age-benefits bloc in the 2010 midterm election in response to threats of Medicare rationing. METHODS: Analysis of age group data from the Edison Research 2010 Election Day exit polls, complemented by data published elsewhere. RESULTS: For the first time in 4 decades, there were signs of an old age voting bloc in the 2010 election; yet, analysis of the age group data by sex and race/ethnicity reveals notable differences among these subgroups. IMPLICATIONS: This new tendency toward old-age bloc voting may well continue in the 2012 election and beyond. If "reforming" Medicare and Social Security persist as policy issues, the votes of older persons may increasingly be affected to a much greater degree than in past elections. PMID- 22048810 TI - Physical activity and older adults: expert consensus for a new research agenda. AB - PURPOSE: This study sought to advance the state of knowledge regarding physical activity and aging by identifying areas of agreement among experts regarding topics that are well understood versus those that are in urgent need of continued research efforts. DESIGN AND METHODS: We used a web-based survey with snowball sampling to identify 348 experts who were invited to complete a brief web-based survey. Responses were received from 38% of invited respondents. RESULTS: Respondents reported that the efficacy and effectiveness of several types of physical activity were well understood but the dose-response relationship required for a health benefit was not. In general, more research is needed examining the effectiveness of programs on cognitive health outcomes and the impact of multiple risk factor programs. With respect to translation, more research is needed on how to maintain older adults in evidence-based programs and how to adapt programs for special populations. Researchers agreed that racial/ethnic minorities; persons with low socioeconomic status; and those with physical, intellectual, or mental health disability were substantially understudied. Finally, research on maintenance, implementation, and reach with respect to these populations was judged to be more urgently needed than research on efficacy and effectiveness. IMPLICATIONS: A substantial amount of consensus was found across a national group of experts. These findings should be instrumental in forging a new research agenda in the area of aging and physical activity. PMID- 22048811 TI - Resident-to-resident aggression in nursing homes: results from a qualitative event reconstruction study. AB - PURPOSE: Despite its prevalence and negative consequences, research on elder abuse has rarely considered resident-to-resident aggression (RRA) in nursing homes. This study employed a qualitative event reconstruction methodology to identify the major forms of RRA that occur in nursing homes. DESIGN AND METHODS: Events of RRA were identified within a 2-week period in all units (n = 53) in nursing homes located in New York City. Narrative reconstructions were created for each event based on information from residents and staff who were involved as well as other sources. The event reconstructions were analyzed using qualitative methods to identify common features of RRA events. RESULTS: Analysis of the 122 event reconstructions identified 13 major forms of RRA, grouped under five themes. The resulting framework demonstrated the heterogeneity of types of RRA, the importance of considering personal, environmental, and triggering factors, and the potential emotional and physical harm to residents. IMPLICATIONS: These results suggest the need for person-centered and environmental interventions to reduce RRA, as well as for further research on the topic. PMID- 22048812 TI - Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro. AB - Increased oxidative stress (OS) in diabetes mellitus is one of the major factors leading to diabetic pathology. However, the mediators and mechanism that provoke OS in diabetes is not fully understood, and it is possible that accumulation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions may incite circulating polymorphonuclear neutrophils (PMN) to generate reactive oxygen species (ROS). In this report, we aim to investigate the effect of AGE on reactive oxygen and nitrogen species generation and subsequent OS in PMN. AGE-HSA exert dose- and time-dependent enhancement of ROS and reactive nitrogen intermediates (RNI) generation by PMN. Increased ROS and RNI generation were found to be mediated through the upregulation of NADPH oxidase and inducible nitric oxide synthase (iNOS), respectively, as evident from the fact that AGE treated neutrophils failed to generate ROS and RNI in presence of diphenyleneiodonium, a flavoprotein inhibitor for both enzymes. Further increased generation of ROS and RNI ceased when the cells were incubated with anti-RAGE antibody suggesting the involvement of AGE-RAGE interaction. Also increased malondialdehyde (MDA) and protein carbonyl formation in AGE-exposed PMN suggest induction of OS by AGE. This study provides evidence that AGEs may play a key role in the induction of oxidative stress through the augmentation of PMN mediated ROS and RNI generation and this may be in part responsible for development of AGE-induced diabetic pathology. PMID- 22048814 TI - Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review. AB - Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients' characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05-1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6-13/20 vs. 10-18/20, before and after 2005, respectively). KI 67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use. PMID- 22048815 TI - Basal-like Breast cancer DNA copy number losses identify genes involved in genomic instability, response to therapy, and patient survival. AB - Breast cancer is a heterogeneous disease with known expression-defined tumor subtypes. DNA copy number studies have suggested that tumors within gene expression subtypes share similar DNA Copy number aberrations (CNA) and that CNA can be used to further sub-divide expression classes. To gain further insights into the etiologies of the intrinsic subtypes, we classified tumors according to gene expression subtype and next identified subtype-associated CNA using a novel method called SWITCHdna, using a training set of 180 tumors and a validation set of 359 tumors. Fisher's exact tests, Chi-square approximations, and Wilcoxon rank sum tests were performed to evaluate differences in CNA by subtype. To assess the functional significance of loss of a specific chromosomal region, individual genes were knocked down by shRNA and drug sensitivity, and DNA repair foci assays performed. Most tumor subtypes exhibited specific CNA. The Basal-like subtype was the most distinct with common losses of the regions containing RB1, BRCA1, INPP4B, and the greatest overall genomic instability. One Basal-like subtype associated CNA was loss of 5q11-35, which contains at least three genes important for BRCA1-dependent DNA repair (RAD17, RAD50, and RAP80); these genes were predominantly lost as a pair, or all three simultaneously. Loss of two or three of these genes was associated with significantly increased genomic instability and poor patient survival. RNAi knockdown of RAD17, or RAD17/RAD50, in immortalized human mammary epithelial cell lines caused increased sensitivity to a PARP inhibitor and carboplatin, and inhibited BRCA1 foci formation in response to DNA damage. These data suggest a possible genetic cause for genomic instability in Basal-like breast cancers and a biological rationale for the use of DNA repair inhibitor related therapeutics in this breast cancer subtype. PMID- 22048816 TI - Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer. AB - Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-alpha, IL 1beta, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8 isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure cancer progression to advanced stages and may result from both host and tumor inflammatory mediators. PMID- 22048817 TI - Age-related loss of muscle fibres is highly variable amongst mouse skeletal muscles. AB - Sarcopenia is the age-related loss of skeletal muscle mass and strength, attributable in part to muscle fibre loss. We are currently unable to prevent fibre loss because we do not know what causes it. To provide a platform from which to better understand the causes of muscle fibre death we have quantified fibre loss in several muscles of aged C57Bl/6J mice. Comparison of muscle fibre numbers on dystrophin-immunostained transverse tissue sections at 6 months of age with those at 24 months shows a significant fibre loss in extensor digitorum longus and soleus, but not in sternomastoid or cleidomastoid muscles. The muscles of the elderly mice were mostly lighter than their younger counterparts, but fibres in the elderly muscles were of about the same cross-sectional area. This study shows that the contribution of fibre death to sarcopenia is highly variable and that there is no consistent pattern of age-related fibre loss between skeletal muscles. PMID- 22048818 TI - Editorial. PMID- 22048819 TI - Relation of Dieting in College and High School Students to Symptoms Associated with Semi-starvation. AB - Dieting and concern with weight were found to be associated with psychological and neurological symptoms observed in cases of severe semi-starvation. College students of both sexes (n 292) and high school females (n121) rated themselves on dietary restraint and psychological and physical symptoms that were prevalent in men after 24 weeks in the Minnesota semi-starvation experiment of 1944-5. Apprehension, irritability, and moodiness were associated with a high concern with restraint. Blank spells, hunger pain, concern for health, and social withdrawal were associated with a history of restraint. Depression, lower self esteem, eating behavior patterns, apathy, and decreased motivation were associated with both restraint parameters. Our results suggest that normal dieting may be more closely related to psychological and health risks associated with chronic semi-starvation than is commonly believed. PMID- 22048820 TI - Dieting and cognitive style: the role of current and past dieting behaviour and cognitions. AB - This study aimed to investigate the relationship between dieting and global cognitive style in a non-clinical sample. Questionnaires were administered to 218 Australian undergraduate students. Dieting was operationalized in two ways: self reported current dieting behaviour; and scores on dietary restraint. It was found that current, but not past, dieters had more dysfunctional cognitive attitudes, confirming the necessity of distinguishing between current and past dieting behaviour. The Concern for Dieting subscale of dietary restraint was also related to a dysfunctional cognitive style, even after level of depressed mood was statistically controlled. In particular, the dysfunctional attitude of Dichotomous Thinking was implicated. Taken together, the findings imply that dieters do not have an enduring maladaptive cognitive style, but rather that current dieting concerns and behaviour are associated with poorer cognitive functioning. PMID- 22048821 TI - Body dissatisfaction within couples: adding the social context to perceptions of self. AB - Nineteen heterosexual couples completed questionnaires concerning their own and their partner's body size. Although women reported higher levels of body dissatisfaction, both men and women reported being dissatisfied with their body parts. Further, the results showed comparability within couples for ratings of the male partner's body size but consistent differences for ratings of the female partner's body size. In addition, both partners reported most dissatisfaction with the female partner's body size. It is suggested that a sexual partner's beliefs may play a greater role in the development of men's body dissatisfaction and that the female body may have become a legitimate source of criticism for both men and women. The implications for the social context on self-perception are discussed. PMID- 22048822 TI - The Impact of Motor Vehicle Accidents on the Psychological Well-being of At-fault Drivers and Related Passengers. AB - This study assessed the effects of motor vehicle accidents (MVAs) on drivers' and passengers' responsibility attribution, and levels of psychological distress and well-being. A total of 321 MVA victims from the state of Queensland, Australia, participated in this study by responding to a questionnaire designed to measure the study's critical variables. Of the sample, 221 were drivers (99 males, 122 females) and 100 were passengers (31 males, 69 females). Of the passengers, 47 percent reported that they were related to the driver, while 53 percent reported that they were not related to the driver. The drivers were categorized by their attribution of responsibility for their accidents, with a resultant 20 percent perceiving themselves to be at fault, and 80 percent perceiving themselves not to be at fault. Results obtained from MANOVAs showed that there was a significant decrease in reported well-being for both passenger- and driver-victims following their accidents. For drivers, the decrease was significantly greater for those who did not accept responsibility for their accidents than those who did. Path analysis showed that blaming others for the accident was associated with higher levels of psychological distress and a lower level of psychological well-being (PWB) for both passengers and drivers. For drivers, accepting responsibility for the accident was associated with lower levels of psychological distress and a higher level of PWB. Implications for the development of coping strategies for MVA victims are discussed. PMID- 22048823 TI - The role of stress and mood in sickle cell disease pain: an analysis of daily diary data. AB - The role of stress and mood in the onset and course of sickle cell disease (SCD) pain was examined using a daily diary design. Fifteen adults with SCD completed daily diaries about their pain, stress, mood, and health care and medication use for an average of 94 days. Multilevel random effects models indicated that stress was significantly and positively related to same-day pain ratings. Stress remained a significant predictor of pain after omitting stressors related to SCD. Mood also showed significant associations with same-day pain in the expected directions. In addition, stress and mood were associated with health care and medication use during painful episodes. Finally, painful episodes were preceded by increases in stress 2 days previously, suggesting that stress may play a role in the onset of SCD pain. PMID- 22048824 TI - Commentary on the role of stress and mood in sickle cell disease pain: an analysis of daily diary data by laura s. Porter, karen m. Gil, james w. Carson, kelly k. Anthony, & jawana ready. PMID- 22048825 TI - Sensitivity to Change Following Liver Transplantation: A Comparison of Three Instruments that Measure Quality of Life. AB - There is an increasing focus on the importance of quality-of-life (QOL) factors in evaluating the efficacy of medical and surgical interventions. There are a wide number of instruments currently available, and the aim of the present study was to evaluate the relative sensitivity to change of three widely used QOL measures, the WHOQOL-100, the SF-36 and the Rotterdam Symptom Checklist, focusing on psychological and physical components of life quality. Fifty patients were assessed pre- and 3 months post-liver transplantation. In addition, 21 patients with liver disease but who were not transplanted were assessed twice, separated by a 3-month interval, in order to serve as a comparison group. All QOL measures showed significant improvement following liver transplantation, whereas the control group showed no significant within-subject change on any measure. We employed the Standardised Response Mean (SRM) effect size as our index of clinically meaningful change in QOL measures. Large SRM effect sizes were obtained following liver transplantation for WHOQOL-100 and SF-36 summary measures, and for the Rotterdam physical subscale. In contrast, the traditional SF-36 scale scores and Rotterdam psychological subscale exhibited only moderate sensitivity to change. PMID- 22048826 TI - Psychological Correlates of Mental Stress-induced Ischemia in the Laboratory: The Psychophysiological Investigation of Myocardial Ischemia (PIMI) Study. AB - Participants consisted of 184 patients (160 males, 24 females) with positive angiograms or prior myocardial infarctions who displayed at least 1 mm of ST segment depression on a standardized treadmill test. Mean scores on the Reward Dependence subscale of the Tridimensional Personality Questionnaire were higher in patients displaying ischemia during mental stress. Patients who reported higher levels of irritability/anger in response to the Speech stressor were also more likely to display ischemia. However, this result was primarily a result of the females in the sample whose ratings of interest and irritability were associated with ischemia during the Speech task. Psychometric measures previously found in prospective studies to predict acute cardiac events were unrelated to mental stress-induced ischemia in the laboratory. PMID- 22048827 TI - What do General Practitioners Discuss with their Patients?: Exploring the Relationship between Content of Medical Consultations and Treatment Decisions. AB - Thirty audiotaped and transcribed general practice consultations were used to develop a classification scheme to code the content of doctor-patient communication in primary care. Open coding was used to identify subject matter discussed by general practitioners in consultations featuring commonly presented problems such as respiratory, psychological and musculoskeletal complaints. The classification scheme was found to have an adequate inter-rater reliability (0.72) and was used in a pilot study to code a further 75 consultations featuring psychological problems as the main presenting complaints. Multivariate analysis of variance showed significant relationships between what was discussed by general practitioners and the type of treatment decisions made (F(16, 51) 2.12, p .01). Consultations in which general practitioners talked to their patients about mental coping strategies, social support and treatment options were less likely to end with decisions to prescribe drugs than consultations in which general practitioners did not discuss these subjects. PMID- 22048828 TI - Psychological impact of predictive testing for colonic cancer. AB - Advances in DNA technology have facilitated presymptomatic testing for an inherited predisposition to a number of autosomal dominant cancer syndromes. While testing is generally undertaken with informed consent and within a counselling protocol, there is still much to be learned about the psychological impact of DNA testing in a predictive setting. In this study, patients' experiences were recorded using in-depth interview techniques following earlier testing for hereditary non-polyposis colorectal cancer which was coordinated through an hereditary cancer registry. Thematic analysis of the transcripts revealed consistent issues pertaining to identity as well as emotional responses to previous preventative strategies and ongoing cancer screening options. PMID- 22048829 TI - Effects of incentive items on participation in a randomized chemoprevention trial. AB - Behavioral research has an important role in increasing and maintaining participation in disease prevention trials, both in interventions and in follow up visits. We conducted a randomized experiment among participants in the lung cancer chemoprevention trial, CARET (Carotene and Retinol Efficacy Trial) to test the effects of providing two incentives on retention. The items used for this study were a Certificate of Appreciation and one of two lapel pins, provided in a 2 2 design. Providing incentives, whether alone or in combination, had no statistically significant effect on retention by the two-year follow-up point. The successful implementation of this randomized incentive study has two implications for future research: (1) study of behavioral interventions and issues is feasible in the context of large controlled trials of disease end points; and (2) such study is necessary to determine whether selected incentives can increase retention. PMID- 22048830 TI - The mad cow crisis: health and the public good. PMID- 22048831 TI - Clinical communication skills. PMID- 22048832 TI - Women's Health: Psychological and Social Perspectives. PMID- 22048833 TI - Smoking in adolescence: images and identities. PMID- 22048834 TI - The menstrual cycle. PMID- 22048836 TI - Cerebral activation and catastrophizing during pain anticipation in patients with fibromyalgia. AB - OBJECTIVE: Anticipation of pain influences its cerebral processing and dysfunctional cognitive style like catastrophizing correlates with the severity of pain. Patients with fibromyalgia syndrome (FMS) exhibit higher levels of catastrophizing, increased attention to pain, and augmented cerebral pain processing. Therefore, alteration in cerebral processing during anticipation of experimental pain and its relation to catastrophizing are the main focus of the study. METHODS: Functional magnetic resonance imaging of the brain was acquired during the time of pain anticipation with announcement of its intensity or not in 12 patients with FMS and 14 healthy controls. Within a two-factorial model (factors "group" and "session"), the main effect of group and the interaction effect were tested in a whole-brain analysis. In addition, activation of the periaqueductal gray (PAG) was analyzed in a region-of-interest analysis. RESULTS: Patients with FMS generally displayed greater catastrophizing behavior (p = .003) but not during the anticipation of the experimental pain (p > .16). Furthermore, patients showed greater activation of the dorsolateral prefrontal cortex (p = .05), the PAG (p = .04), and the posterior parietal cortex (p = .03) during the anticipation of pain, independent of the pain coping behavior during anticipation. CONCLUSIONS: The lack of difference in catastrophizing during the experimental pain suggests independent coping mechanisms during experimental and clinical pain. Regarding the importance of the frontal cortex and the PAG in the descending pain modulation system, it seems reasonable to assume that these functional changes related to the context of stimulus presentation may contribute to central sensitization in FMS. PMID- 22048837 TI - Patterns of emotional-cognitive functioning in pediatric conversion patients: implications for the conceptualization of conversion disorders. AB - OBJECTIVES: To examine patterns of emotion processing in children and adolescents with conversion disorders and to determine whether those patterns are associated with particular clusters of conversion symptoms. Autobiographical narratives were used to investigate the organization of information about distressing feelings and memories. METHODS: Structured interviews about attachment relationships and autobiographical events were administered to 76 controls and 76 matched subjects aged 6 to 18 years. Age-appropriate assessments of attachment were used: the School-aged Assessment of Attachment for children and the Transition to Adulthood Attachment Interview for adolescents. Patterns of emotion processing were identified using dynamic-maturational model discourse analysis and categorized into four clusters: inhibitory, normative/balanced, coercive-preoccupied, and mixed inhibitory and coercive-preoccupied. These clusters were then cross tabulated with the sensorimotor characteristics of children with conversion disorders. RESULTS: Emotion processing in children with conversion disorders was categorized as psychological inhibition (57%), psychological coercion preoccupation (34%), and mixed (9%). Psychological inhibition was associated with negative conversion symptoms (discrete sensorimotor deficits, p = .003) and positive conversion symptoms (tremors and tics, p = .04). Psychological coercion preoccupation was associated with all other disturbances of motor function: bizarre gaits and postures, whole-body floppiness, and refusals to move (p < .0001). Nonepileptic seizures occurred across both groups (56% versus 42%, p = .8). CONCLUSIONS: Contrary to the classic understanding of conversion disorder as a unified diagnostic entity with diverse symptoms, this study identified two distinct subtypes of conversion patients-those using psychological inhibition and those using psychological coercion-preoccupation-whose symptoms fell into discrete clusters. Further research is needed to determine the neural mechanisms underlying these processes. PMID- 22048838 TI - Evaluating new proposals for the psychiatric classification of patients with multiple somatic symptoms. AB - OBJECTIVES: The current DSM-IV classification of somatoform disorders has been criticized, and several new proposals for classification have been suggested (e.g., DSM-V work group: complex somatic symptom disorder [CSSD]). Our aim was to empirically validate and compare new proposals for the classification of people with multiple somatic complaints. METHODS: Three hundred twenty-one participants were selected from a general population sample of more than 2500; half were selected from a subgroup with increased somatization scores (Patient Health Questionnaire 15-item somatic symptom subscale). Clinical and psychological variables and health care use were assessed with interviews and self-ratings to validate the new proposals. In addition, a high-risk group was defined to check whether new classification proposals could identify people in this a priori defined group; criteria for this high-risk group were disabling medically unexplained somatic symptoms and increased health care use. To analyze the stability of the syndromes, participants were recontacted 1 year later (completion rate, 76%). RESULTS: The DSM-V proposal for CSSD shows good validity in the identification of people with disability and people requiring medical treatment. It is still restrictive but to a much lesser degree than the current somatization disorder: 29% of our a priori high-risk group was identified, whereas none of the participants fulfilled criteria for somatization disorder. For most proposals, the temporal stability is satisfactory yet substantially lower than expected for clinical samples. Classification criteria that include psychological features are advantageous in identifying people with health care needs. CONCLUSIONS: Whereas some validation criteria for the new proposals (including CSSD) are satisfactory, most of the new proposals are still restrictive. PMID- 22048835 TI - Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity. AB - Transition metals are essential nutrients to virtually all forms of life, including bacterial pathogens. In Staphylococcus aureus, metal ions participate in diverse biochemical processes such as metabolism, DNA synthesis, regulation of virulence factors, and defense against oxidative stress. As an innate immune response to bacterial infection, vertebrate hosts sequester transition metals in a process that has been termed "nutritional immunity." To successfully infect vertebrates, S. aureus must overcome host sequestration of these critical nutrients. The objective of this review is to outline the current knowledge of staphylococcal metal ion acquisition systems, as well as to define the host mechanisms of nutritional immunity during staphylococcal infection. PMID- 22048839 TI - Effects of mindfulness training on body awareness to sexual stimuli: implications for female sexual dysfunction. AB - OBJECTIVES: Treatments of female sexual dysfunction have been largely unsuccessful because they do not address the psychological factors that underlie female sexuality. Negative self-evaluative processes interfere with the ability to attend and register physiological changes (interoceptive awareness). This study explores the effect of mindfulness meditation training on interoceptive awareness and the three categories of known barriers to healthy sexual functioning: attention, self-judgment, and clinical symptoms. METHODS: Forty-four college students (30 women) participated in either a 12-week course containing a "meditation laboratory" or an active control course with similar content or laboratory format. Interoceptive awareness was measured by reaction time in rating physiological response to sexual stimuli. Psychological barriers were assessed with self-reported measures of mindfulness and psychological well-being. RESULTS: Women who participated in the meditation training became significantly faster at registering their physiological responses (interoceptive awareness) to sexual stimuli compared with active controls (F(1,28) = 5.45, p = .03, eta(p)(2) = 0.15). Female meditators also improved their scores on attention (t = 4.42, df = 11, p = .001), self-judgment, (t = 3.1, df = 11, p = .01), and symptoms of anxiety (t = -3.17, df = 11, p = .009) and depression (t = -2.13, df = 11, p < .05). Improvements in interoceptive awareness were correlated with improvements in the psychological barriers to healthy sexual functioning (r = -0.44 for attention, r = -0.42 for self-judgment, and r = 0.49 for anxiety; all p < .05). CONCLUSIONS: Mindfulness-based improvements in interoceptive awareness highlight the potential of mindfulness training as a treatment of female sexual dysfunction. PMID- 22048840 TI - Effects of ozone on species composition in an upland grassland. AB - Northern hemispheric background concentrations of ozone are increasing, but few studies have assessed the ecological significance of these changes for grasslands of high conservation value under field conditions. We carried out a 3-year field experiment in which ozone was released at a controlled rate over three experimental transects to produce concentration gradients over the field site, an upland mesotrophic grassland located in the UK. We measured individual species biomass in an annual hay cut in plots receiving ambient ozone, and ambient ozone elevated by mean concentrations of approximately 4 ppb and 10 ppb in the growing seasons of 2008 and 2009. There was a significant negative effect of ozone exposure on herb biomass, but not total grass or legume biomass, in 2008 and 2009. Within the herb fraction, ozone exposure significantly decreased the biomass of Ranunculus species and that of the hemi-parasitic species Rhinanthus minor. Multivariate analysis of species composition, taking into account spatial variation in soil conditions and ozone exposure, showed no significant ozone effect on the grass component. In contrast, by 2009, ozone had become the dominant factor influencing species composition within the combined herb and legume component. Our results suggest that elevated ozone concentrations may be a significant barrier to achieving increased species diversity in managed grasslands. PMID- 22048841 TI - Enantioselective pharmacokinetic and pharmacodynamic properties of carvedilol in spontaneously hypertensive rats: focus on blood pressure variability. AB - The cardiovascular effects and pharmacokinetics of carvedilol were assessed in spontaneously hypertensive (SH) and Wistar Kyoto (WKY) animals with special focus on short-term blood pressure variability (BPV). Male SH and WKY rats were acutely treated with vehicle or carvedilol 1 or 5 mg kg(-1) (i.v.), and effects on blood pressure (BP), heart rate (HR) and BPV were recorded. Plasma pharmacokinetics of R- and S-carvedilol was studied by traditional blood sampling. Relationship between carvedilol concentrations and their hypotensive and bradycardic effects was established by pharmacokinetic-pharmacodynamic (PK-PD) modelling. Short-term BPV was assessed by standard deviation of BP recording. Vascular sympatholytic activity of carvedilol was studied by estimation of drug effects on ratio between low frequency (LF) and high frequency (HF) BPV (LF/HF ratio). Although pharmacokinetic properties of carvedilol remained mainly unaffected in SH rats with regard to WKY rats, hypertensive animals showed a reduction in drug clearance of R- and S-carvedilol after administration of 1 mg kg(-1) compared with WKY rats. PK-PD analysis of HR changes induced by S-carvedilol showed a greater maximal bradycardic response to carvedilol in SH rats (E (max), -27.6 +/- 3.9%; p < 0.05) compared with WKY group (E (max), -13.4 +/- 2.5%). SH rats showed a greater hypotensive effect of racemic carvedilol (E (max), -45.5 +/- 5.0%; p < 0.05) with regard to WKY group (E (max), -17.9 +/- 4.5%). Carvedilol induced a greater reduction of LF/HF ratio in SH rats compared with WKY rats. Short-term BPV was markedly reduced by carvedilol in WKY and SH rats. In conclusion, as a consequence of an enhanced bradycardic response and a greater vascular sympatholytic activity, carvedilol exerts a greater hypotensive response in SH rats compared with WKY animals and dramatically reduces short-term BPV. PMID- 22048842 TI - Novel approach for quantification of hepatitis C virus in liver cirrhosis using real-time reverse transcriptase PCR. AB - BACKGROUND: Hepatitis C virus (HCV) infects nearly 3% of the population worldwide and is a major cause of acute and chronic infections leading to fibrosis, cirrhosis, and hepatocellular carcinoma. Current laboratory diagnosis of HCV is based on specific antibody detection (anti-hepatitis C virus (anti-HCV)) in serum. As HCV replicates in the liver cells, detection and localization of HCV RNA in liver tissue are vital for diagnosis. METHODS: Ten biopsy samples diagnosed for cryptogenic liver cirrhosis, negative for the presence of anti-HCV and serum HCV RNA, were studied for analyzing presence of viral nucleic acid in liver tissues. Qualitative screening for HCV was done through ELISA while the nucleic acid analysis was performed through COBAS Amplicor. Detection of HCV RNA in liver tissue biopsies was performed following standard protocol of HCV detection kit (Shenzhen PG Biotech) with modifications using Light Cycler 2.0 (minimum detection limit 10 copies/ml). RESULT: Quantitative detection in liver biopsies following the modified method showed the presence of HCV RNA in three samples out of the ten studied. CONCLUSION: The results indicate that using Light Cycler 2.0, following the modified technique described, constitutes a reliable method of quantitative detection and localization of HCV in tissue in "serosilent" HCV infection. PMID- 22048843 TI - Distribution of UL144, US28 and UL55 genotypes in Polish newborns with congenital cytomegalovirus infections. AB - Human cytomegalovirus (HCMV) is the most common congenital infection. HCMV strains display genetic variability in different regions. Distribution of HCMV genotypes in the population of congenitally infected newborns from Central Poland and viral load in newborns' blood is described and discussed. HCMV isolates were analysed by sequencing at three sites on the genome: the UL144 tumour necrosis factor-alpha (TNFalpha)-like receptor gene, the US28 beta-chemokine receptor gene and the UL55 envelope glycoprotein B (gB) gene. The newborns' blood was examined for HCMV DNA with a nested (UL144, UL55) or heminested (US28) polymerase chain reaction, and the genotypes were determined by sequence analysis. HCMV DNA was detectable in 25 out of 55 examined newborns born by HCMV-infected mothers (45.5%). The blood viral load in mother-infant pairs was determined. Most of the newborns had identical virus genotype, gB2 (96%), UL144 B1 (88%) and US28 A2 (84%). These genotypes were detected in all newborns with asymptomatic congenital infection. The occurrence of UL144 B1 or US28 A2 genotypes in the babies examined was significant in comparison to other genotypes (p=0.0002 and p=0.040 respectively). There was no association between specific gB subtypes in all patients groups (p=0.463). There was no correlation between HCMV genotypes and the outcome. PMID- 22048844 TI - Use of linezolid in neonatal and pediatric inpatient facilities--results of a retrospective multicenter survey. AB - The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6-15.5 years; range 0.1-21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved. PMID- 22048846 TI - Regioselective glucosidation of trans-resveratrol in Escherichia coli expressing glucosyltransferase from Phytolacca americana. AB - A glucosyltransferase (GT) of Phytolacca americana (PaGT3) was expressed in Escherichia coli and purified for the synthesis of two O-beta-glucoside products of trans-resveratrol. The reaction was moderately regioselective with a ratio of 4'-O-beta-glucoside: 3-O-beta-glucoside at 10:3. We used not only the purified enzyme but also the E. coli cells containing the PaGT3 gene for the synthesis of glycoconjugates. E. coli cell cultures also have other advantages, such as a shorter incubation time compared with cultured plant cells, no need for the addition of exogenous glucosyl donor compounds such as UDP-glucose, and almost complete conversion of the aglycone to the glucoside products. Furthermore, a homology model of PaGT3 and mutagenesis studies suggested that His-20 would be a catalytically important residue. PMID- 22048847 TI - Natural plant genetic engineer Agrobacterium rhizogenes: role of T-DNA in plant secondary metabolism. AB - Agrobacterium rhizogenes is a natural plant genetic engineer. It is a gram negative soil bacterium that induces hairy root formation. Success has been obtained in exploring the molecular mechanisms of transferred DNA (T-DNA) transfer, interaction with host plant proteins, plant defense signaling and integration to plant genome for successful plant genetic transformation. T-DNA and corresponding expression of rol genes alter morphology and plant host secondary metabolism. During transformation, there is a differential loss of a few T-DNA genes. Loss of a few ORFs drastically affect the growth and morphological patterns of hairy roots, expression pattern of biosynthetic pathway genes and accumulation of specific secondary metabolites. PMID- 22048845 TI - Cardiovascular consequences of sleep apnea. AB - Sleep apnea is a common health concern that is characterized by repetitive episodes of asphyxia. This condition has been linked to serious long-term adverse effects such as hypertension, metabolic dysregulation, and cardiovascular disease. Although the mechanism for the initiation and aggravation of cardiovascular disease has not been fully elucidated, oxidative stress and subsequent endothelial dysfunction play major roles. Animal models, which have the advantage of being free of comorbidities and/or behavioral variables (that commonly occur in humans), allow invasive measurements under well-controlled experimental conditions, and as such are useful tools in the study of the pathophysiological mechanisms of sleep apnea. This review summarizes currently available information on the cardiovascular consequences of sleep apnea and briefly describes common experimental approaches useful to sleep apnea in different animal models. PMID- 22048848 TI - Construction of multi-functional extracellular matrix proteins that inhibits migration and tube formation of endothelial cells. AB - Artificial extracellular matrix (ECM) proteins have been designed that have strong cell-adhesive activity and active functional units that inhibit network formation among vascular endothelial cells. A laminin-derived sequence (YIGSR) that blocks migration of vascular endothelial cells was designed to incorporate into an elastin-derived structural unit. The designed ECM fusion protein also had a cell-adhesive RGDN sequence that conferred an intense migration-inhibitory effect. The resultant ECM showed cell-adhesive activity superior to that of the synthetic YIGSR peptide and it blocked the migration of vascular endothelial cells. Furthermore, the designed ECM inhibited the angiogenic activity of a collagen gel. The engineering strategy of designing multi-functional ECM proteins could be applied to support novel tissue engineering techniques. PMID- 22048849 TI - Coronary CT angiography in patients with high calcium score: evaluation of plaque characteristics and diagnostic accuracy. AB - Our aim was to evaluate the plaque characteristics of coronary arteries related to significant stenosis with coronary CT angiography (CCTA) and to discuss the diagnostic accuracy of CCTA in patients with high calcium scores. After institutional review board approval, 110 patients (63 men; mean age: 67.1 +/- 7.9 years) with Agatston scores >400 were retrospectively reviewed. Patients underwent Agatston calcium scoring and 64-slice CCTA, in addition to invasive coronary angiography (CAG). The composition (calcified, mixed, and non-calcified) and configuration (concentric, eccentric) of coronary artery plaques were analyzed on a per-segment basis by CCTA. We analyzed the differences in plaque composition and configuration between significant (>= 50%) and non-significant (<50%) stenosis. Additionally, the diagnostic accuracy of stenosis according to plaque composition was evaluated by CCTA, using CAG as a reference method. Significant differences in plaque composition and configurations were observed between the two groups. In cases of significant stenosis, the proportions of concentric, mixed, and non-calcified plaques were significantly higher than those of eccentric and calcified plaques (P < 0.001). The sensitivity and positive predictive value of mixed (97.4, 87.6%) and non-calcified plaques (97.8, 95.7%) were significantly higher than those of calcified plaques (87.6, 67.2%). Although CCTA has limited value due to low diagnostic accuracy of calcified plaques, knowledge about the high frequencies of mixed and non-calcified plaques in significant stenosis help to make an accurate assessment of CAD with CCTA in patients with high calcium scores. PMID- 22048850 TI - Psychotropic drugs and paediatrics: a critical need for more clinical trials. AB - Many children in the USA are prescribed psychotropic drugs that have not been fully investigated in paediatric clinical trials. The common practice of prescribing psychotropic drugs off-label poses unknown and potentially serious short- and long-term consequences for these children. This paper briefly reviews the factors associated with the lack of paediatric clinical trials. We advocate a shift toward increasing paediatric trials with psychotropic drugs through a combination of adequate safety controls, additional reimbursement/compensation, a more organised and large-scale effort to collate results and outcomes across researchers and studies and additional public education about the importance of this research. In addition, we encourage the re-examination of the ethical standards for children's participation in phase 1 clinical trials as well as argue for longitudinal developmental studies on children who are prescribed off label psychotropic drugs. PMID- 22048851 TI - The principle of parity: the 'placebo effect' and physician communication. AB - The use of 'placebos' in clinical practice is a source of continued controversy for physicians and medical ethicists. There is rarely any extensive discussion on what 'placebos' are and how they work. In this paper, drawing on Louhiala and Puustinen's work, the author proposes that the term 'placebo effect' be replaced in clinical contexts with the term 'positive care effect'. Medical treatment always takes place in a 'context of care' that encompasses all the phenomena associated with medical intervention it includes the particular method of treatment, the interpersonal relationships between medical staff and the patient and other factors, including physicians' and patients' beliefs in the power of the treatment. Together, these phenomena can result in a full spectrum of therapeutic effects to the patient--from no effects, to small effects, to large effects. In cases where there are significant therapeutic benefits to the patient, 'positive care effects' may be spoken of. Since the ethical codes of the General Medical Council and the American Medical Association demand transparency with respect to patient treatment and insist on complete openness in 'placebo' usage, the author argues that, as a matter of conceptual rigour and consistency, if the term 'placebo effect' is replaced by 'positive care effect', these ethical codes appear to insist on transparency about all such beneficial components of treatment. Given that this appears to be a counterintuitive obligation, the author concludes the paper with some comments on the clinical consequences of this conceptual revision, including a brief discussion of how this important debate might develop. PMID- 22048852 TI - Tacitly opting out of organ donation: too presumptuous after all? PMID- 22048854 TI - Dissent about assent in paediatric research. PMID- 22048853 TI - In the lion's den? Experiences of interaction with research ethics committees. AB - Research ethics review is an important process, designed to protect participants in medical research. However, it is increasingly criticised for failing to meet its aims. Here, two researchers reflect on their experiences of applying for ethical approval of observational research in clinical settings. They highlight some problems faced by reviewers and researchers and propose a two-stage ethical review process that would alert researchers to the committee's concerns and allow them to give a more considered response. PMID- 22048855 TI - [Progress in therapy and diagnostics of neuropsychiatric diseases]. PMID- 22048856 TI - [Deep brain stimulation in schizophrenia]. AB - Deep brain stimulation (DBS) has successfully advanced our treatment options for putative therapy-resistant neuropsychiatric diseases. Building on this strong foundation, more and more mental disorders in the stadium of therapy-resistance are considered as possible indications for DBS. Especially, schizophrenia with its associated severe and difficult to treat symptoms is gaining attention. This attention demands critical questions regarding the assumed mechanisms of DBS and its possible influence on the supposed pathophysiology of schizophrenia. Here, we synoptically compare current approaches and theories of DBS and discuss the feasibility of DBS in schizophrenia as well as the transferability from other psychiatric disorders successfully treated with DBS. For this we consider recent advances in animal models of schizophrenic symptoms, results regarding the influence of DBS on dopaminergic transmission as well as data concerning neural oscillation and synchronisation. In conclusion, the use of DBS for some symptoms of schizophrenia seems to be a promising approach, but the lack of a comprehensive theory of the mechanisms of DBS as well as its impact on schizophrenia might hinder the use of DBS for schizophrenia at this point in time. PMID- 22048857 TI - [Retrospective analysis of routine-MRI and correlation with aetiology of dementia, severity and neuropsychology in a memory-clinic population]. AB - BACKGROUND: The contribution of potential treatable dementia aetiologies diagnosed using cerebral imaging varied considerably in previous studies and was not evaluated in a recent larger German sample of patients from a memory clinic. MATERIAL AND METHODS: MRI images of 502 patients were retrospectively reassessed. Beside the proportion of potentially treatable dementia aetiology, the extent of whole brain atrophy (semiquantitative) and vascular white matter lesions were assessed. RESULTS: Mean age of the patients was 63.7 +/- 13.1 years; 49 % were female, mean MMST was 24.2 +/- 5.5. In 74 % there was an agreement between the clinical dementia syndrome and MRI. 9 % (45 patients) had clearly discrepant imaging results, according to MRI criteria (21 * ischaemia, 20 * normal pressure hydrocephalus (NPH), 4 * intracerebral haemorrhage). These patients could not not be differentiated using age and MMST alone as clinical criteria. There was a significant correlation between global brain atrophy and MMST (r = -0.32; p < 0.001) and white matter lesion score (r = 0.28; p < 0.001). CONCLUSION: In 9 % there was a clear discrepancy between MRI results and the clinical syndrome diagnosis in memory-clinic patients. As known from earlier studies and current German 3 rd generation guidelines, it is reasonable to perform MRI imaging in dementia to improve the aetiological and differential diagnoses and to detect a different aetiology that can be missed using the clinical dementia criteria alone. PMID- 22048858 TI - [Metabolic myopathies - part II: disorders of the fat, purine, and oxidative energy metabolism]. PMID- 22048859 TI - The ability of land plants to synthesize glucuronoxylans predates the evolution of tracheophytes. AB - Glucuronoxylans with a backbone of 1,4-linked beta-D-xylosyl residues are ubiquitous in the secondary walls of gymnosperms and angiosperms. Xylans have been reported to be present in hornwort cell walls, but their structures have not been determined. In contrast, the presence of xylans in the cell walls of mosses and liverworts remains a subject of debate. Here we present data that unequivocally establishes that the cell walls of leafy tissue and axillary hair cells of the moss Physcomitrella patens contain a glucuronoxylan that is structurally similar to glucuronoxylans in the secondary cell walls of vascular plants. Some of the 1,4-linked beta-D-xylopyranosyl residues in the backbone of this glucuronoxylan bear an alpha-D-glucosyluronic acid (GlcpA) sidechain at O-2. In contrast, the lycopodiophyte Selaginella kraussiana synthesizes a glucuronoxylan substituted with 4-O-Me-alpha-D-GlcpA sidechains, as do many hardwood species. The monilophyte Equisetum hyemale produces a glucuronoxylan with both 4-O-Me-alpha-D-GlcpA and alpha-D-GlcpA sidechains, as does Arabidopsis. The seedless plant glucuronoxylans contain no discernible amounts of the reducing end sequence that is characteristic of gymnosperm and eudicot xylans. Phylogenetic studies showed that the P. patens genome contains genes with high sequence similarity to Arabidopsis CAZy family GT8, GT43 and GT47 glycosyltransferases that are likely involved in xylan synthesis. We conclude that mosses synthesize glucuronoxylan that is structurally similar to the glucuronoxylans present in the secondary cell walls of lycopodiophytes, monilophytes, and many seed-bearing plants, and that several of the glycosyltransferases required for glucuronoxylan synthesis evolved before the evolution of tracheophytes. PMID- 22048860 TI - Linolenate 9R-dioxygenase and allene oxide synthase activities of Lasiodiplodia theobromae. AB - Jasmonic acid (JA) is synthesized from linolenic acid (18:3n-3) by sequential action of 13-lipoxygenase, allene oxide synthase (AOS), and allene oxide cyclase. The fungus Lasiodiplodia theobromae can produce large amounts of JA and was recently reported to form the JA precursor 12-oxophytodienoic acid. The objective of our study was to characterize the fatty acid dioxygenase activities of this fungus. Two strains of L. theobromae with low JA secretion (~0.2 mg/L medium) oxygenated 18:3n-3 to 5,8-dihydroxy-9Z,12Z,15Z-octadecatrienoic acid as well as 9R-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid, which was metabolized by an AOS activity into 9-hydroxy-10-oxo-12Z,15Z-octadecadienoic acid. Analogous conversions were observed with linoleic acid (18:2n-6). Studies using [11S (2)H]18:2n-6 revealed that the putative 9R-dioxygenase catalyzed stereospecific removal of the 11R hydrogen followed by suprafacial attack of dioxygen at C-9. Mycelia from these strains of L. theobromae contained 18:2n-6 as the major polyunsaturated acid but lacked 18:3n-3. A third strain with a high secretion of JA (~200 mg/L) contained 18:3n-3 as a major fatty acid and produced 5,8-dihydroxy 9Z,12Z,15Z-octadecatrienoic acid from added 18:3n-3. This strain also lacked the JA biosynthetic enzymes present in higher plants. PMID- 22048861 TI - Extended report from working group 5: social responsibility of scientists at the 59th Pugwash Conference on Science and World Affairs in Berlin, 1-4 July 2011. PMID- 22048862 TI - Outcomes in 125 individuals with adrenal incidentalomas from a single centre. a retrospective assessment of the 1 mg overnight and low dose dexamethasone suppression tests. AB - Adrenal masses discovered incidentally during imaging studies - adrenal incidentalomas (AIs) - are common and prompt investigations to exclude secretory lesions and malignancy. Their best management strategy is unknown. Our objectives were to identify all outcomes of AI investigation in a UK centre and to assess the performance of the 2 mg low dose (LDDST) and 1 mg overnight dexamethasone (ODST) suppression tests in this setting. Out of 125 patients referred to our centre between 2005 and 2009 with AIs, 16 (12.8%) were diagnosed with secretory adrenal adenomas. 24 patients (23%) failed to suppress on LDDST or ODST using a serum cortisol cut-off of 50 nmol/l for both tests; in 12 this was due to false positive results. 5 patients were diagnosed with adrenal Cushing's syndrome and 7 with subclinical hypercortisolism. The use of a higher post LDDST (83 nmol/l) or ODST (138 nmol/l) cortisol cut-off would have resulted in missing 1 patient with Cushing's syndrome and 4 with subclinical hypercortisolism or 2 patients with Cushing's syndrome and 1 with subclinical hypercortisolism, respectively. In patients who had both tests, the ODST systematically resulted in higher post-test cortisol values compared with the LDDST. The adenoma diameter correlated with and was predictive of the post LDDST cortisol. Our results indicate that altering the post dexamethasone cut-off in accordance to published guidelines changes the performance of the suppression tests. The ODST may result in higher post-test cortisol levels compared to LDDST when used in patients with AIs. PMID- 22048863 TI - Much more than a gene: hereditary breast and ovarian cancer, reproductive choices and family life. AB - This article presents the results of a study that investigates the way in which carriers of a mutation on the BRCA1 or the BRCA2 gene, associated with a high risk of breast and ovarian cancer, make their reproductive decisions. Using semi structured interviews, the study explored the way in which these persons reflected on the acceptability of taking the risk of transmitting this mutation to the next generation, the arguments they used in favor or against taking that risk, and in the light of these arguments, their opinion on the acceptability of preimplantation genetic diagnosis (PGD) as a reproductive option. The findings suggest that when carriers are planning to have a(nother) child, they are mainly concerned by the risk of transmitting 'much more than a gene': essentially painful experiences not only with respect to health, such as undergoing cancer surveillance or combatting one's own illness, but also with regards to family life, such as witnessing the illness and death of a close relative, encountering difficulties in finding a partner or reconsidering one's plans to have a family. As for opinions concerning the acceptability of PGD as a reproductive option, opinions about personal recourse were varied but all expressed the understanding that PGD should be made available to those persons who consider it their best option. PMID- 22048865 TI - Proximal component modularity in THA--at what cost? An implant retrieval study. AB - BACKGROUND: While modular femoral heads have been used in THA for decades, a recent innovation is a second neck-stem taper junction. Clinical advantages include intraoperative adjustment of leg length, femoral anteversion, and easier revision, all providing flexibility to the surgeon; however, there have been reports of catastrophic fracture, cold welding, and corrosion and fretting of the modular junction. QUESTIONS/PURPOSES: We asked whether (1) the neck-stem junction showed the same degradation mechanisms, if any, as the head-neck junction, (2) the junction contributed to THA revision, (3) the alloy affected the degree of degradation, and (4) the trunion machine finish affected the degradation mechanisms. METHODS: We compared 57 retrievals from seven total hip modular designs, three cobalt-chromium-molybdenum and four titanium based: Bionik((r)) (four), GMRS((r)) (four), Margron((r)) (22), Apex((r)) (five), M-series((r)) (five), ZMR((r)) (two), and S-ROM((r)) (15). Macroscopic inspection, microscopy, and micro-CT were conducted to determine the effects of materials and design. RESULTS: The cobalt-chromium-molybdenum components showed crevice corrosion and fretting of the neck-stem taper, whereas the titanium components had less corrosion; however, there were several cases of cold welding where disassembly could not be achieved in theater. CONCLUSIONS: Even with modern taper designs and corrosion-resistant materials, corrosion, fretting, and particulate debris were observed to a greater extent in the second neck-stem junction. Titanium-based modular arthroplasty may lessen the degree of degradation, but cold welding of the components may occur. CLINICAL RELEVANCE: Degradation of the second junction contributed to 8 cases of metallosis and two cases of aseptic lymphocyte laminated vascular-associated lesions contributing to revision. PMID- 22048864 TI - Basic aspects of tumor cell fatty acid-regulated signaling and transcription factors. AB - This article reviews the current knowledge and experimental research about the mechanisms by which fatty acids and their derivatives control specific gene expression involved during carcinogenesis. Changes in dietary fatty acids, specifically the polyunsaturated fatty acids of the omega-3 and omega-6 families and some derived eicosanoids from lipoxygenases, cyclooxygenases, and cytochrome P-450, seem to control the activity of transcription factor families involved in cancer cell proliferation or cell death. Their regulation may be carried out either through direct binding to DNA as peroxisome proliferator-activated receptors or via modulation in an indirect manner of signaling pathway molecules (e.g., protein kinase C) and other transcription factors (nuclear factor kappa B and sterol regulatory element binding protein). Knowledge of the mechanisms by which fatty acids control specific gene expression may identify important risk factors for cancer and provide insight into the development of new therapeutic strategies for a better management of whole body lipid metabolism. PMID- 22048866 TI - Does shelf acetabuloplasty influence acetabular growth and remodeling? AB - BACKGROUND: Shelf acetabuloplasty has the potential to cause iatrogenic acetabular growth arrest, although accelerated acetabular growth has been reported based on plain radiographic evaluations in patients with Legg-Calve Perthes disease. Because plain radiographs may be limited in depicting actual acetabular morphology, it is unclear whether there are growth disturbances. QUESTIONS/PURPOSES: We therefore determined (1) whether focal or generalized acetabular growth stimulation or retardation occurred based on CT analysis in combination with plain radiographic assessment; and (2) whether radiographically assessed femoral head deformity, subluxation, and acetabular dysplasia were associated with residual zonal rim dysplasia of the acetabulum. METHODS: We examined 14 patients who had undergone shelf acetabuloplasty for "reducible subluxation" and underwent CT scans at a mean 7 years after surgery (range, 3-11 years). We measured radiographic indices reflecting acetabular depth and rim dysplasia on multiplanar reformatted images in 10 radial planes and on plain radiographs and calculated their operation-to-control ratios to assess growth changes. The mean age at surgery was 9.3 years (range, 7-12 years). RESULTS: We observed generalized accelerated growth in 11 hips and equivocal growth in three. None of the 14 hips showed an abrupt change in acetabular geometry. Despite improved acetabular depth in all hips, eight hips had focal rim dysplasia in the superior zone on CT examinations, and this was associated with a smaller center edge angle, a greater deformity index, and preexisting acetabular dysplasia. CONCLUSIONS: Our observations support the notion that shelf acetabuloplasty has a favorable, stimulatory effect on acetabular growth. However, the possible persistence of preexisting zonal rim dysplasia should be considered. PMID- 22048868 TI - A single institution experience of streptozocin/fluorouracil combination chemotherapy: a case series. AB - BACKGROUND: The combination chemotherapy regimen of streptozocin and 5 fluorouracil (FU/STZ) has been used for the treatment of metastatic neuroendocrine tumours. AIM: The aim of this study was to analyse the use of this regimen in a tertiary oncology referral centre over a 10-year period. METHOD: We retrospectively analysed nine cases from February 2000 to May 2010. Patient demographics, chemotherapy schedule, toxicities, progression-free and overall survival were tabulated for each patient. RESULT: The median progression-free survival was 17 months (range 3-48+ months), and overall survival 31 months (range 12-53+ months) with no toxicity related deaths. CONCLUSION: FU/STZ was a well-tolerated regimen that produced significant benefit in the setting of metastatic and progressive disease. Our case series demonstrated comparable progression-free survival and overall survival in relation to randomized controlled studies and previous case series. PMID- 22048869 TI - Toward developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens. AB - BACKGROUND: Previously, we demonstrated the ability of radiolabeled antibodies recognizing the cryptococcal polysaccharide capsule to kill Cryptococcus neoformans both in vitro and in infected mice. This approach, known as radioimmunotherapy (RIT), uses the exquisite ability of antibodies to bind antigens to deliver microbicidal radiation. To create RIT reagents which would be efficacious against all major medically important fungi, we have selected monoclonal antibodies (mAbs) to common surface fungal antigens such as heat shock protein 60 (HSP60), which is found on the surface of diverse fungi; beta (1,3) glucan, which is a major constituent of fungal cell walls; ceramide which is found at the cell surface, and melanin, a polymer present in the fungal cell wall. METHODS: MAbs 4E12, an IgG2a to fungal HSP60; 2G8, an IgG2b to beta-(1,3) glucan; and 6D2, an IgM to melanin, were labeled with the alpha particle emitting radionuclide 213-Bismuth ((213)Bi) using the chelator CHXA". B11, an IgM antibody to glucosylceramide, was labeled with the beta emitter 188-Rhenium ((188)Re). Model organisms Cryptococcus neoformans and Candida albicans were used to assess the cytotoxicity of these compounds after exposure to either radiolabeled mAbs or controls. RESULTS: (213)Bi-mAbs to HSP60 and to the beta-(1,3)-glucan each reduced the viability of both fungi by 80-100%. The (213)Bi-6D2 mAb to melanin killed 22% of C. neoformans, but did not kill C. albicans. B11 mAb against fungal ceramide was effective against wild-type C. neoformans, but was unable to kill a mutant lacking the ceramide target. Unlabeled mAbs and radiolabeled irrelevant control mAbs caused no killing. CONCLUSION: Our results suggest that it is feasible to develop RIT against fungal pathogens by targeting common antigens and such an approach could be developed against fungal diseases for which existing therapy is unsatisfactory. PMID- 22048870 TI - Arsenic speciation analysis of urine samples from individuals living in an arsenic-contaminated area in Bangladesh. AB - OBJECTIVES: Chronic inorganic arsenic (iAs) exposure currently affects tens of millions of people worldwide. To accurately determine the proportion of urinary arsenic metabolites in residents continuously exposed to iAs, we performed arsenic speciation analysis of the urine of these individuals and determined whether a correlation exists between the concentration of iAs in drinking water and the urinary arsenic species content. METHODS: The subjects were 165 married couples who had lived in the Pabna District in Bangladesh for more than 5 years. Arsenic species were measured using high-performance liquid chromatography and inductively coupled plasma mass spectrometry. RESULTS: The median iAs concentration in drinking water was 55 MUgAs/L (range <0.5-332 MUgAs/L). Speciation analysis revealed the presence of arsenite, arsenate, monomethylarsonic acid (MMA), and dimethylarsinic acid in urine samples with medians (range) of 16.8 (7.7-32.3), 1.8 (<0.5-3.3), 13.7 (5.6-25.0), and 88.6 MUgAs/L (47.9-153.4 MUgAs/L), respectively. No arsenobetaine or arsenocholine was detected. The concentrations of the 4 urinary arsenic species were significantly and linearly related to each other. The urinary concentrations of total arsenic and each species were significantly correlated with the iAs concentration of drinking water. CONCLUSIONS: All urinary arsenic species are well correlated with each other and with iAs in drinking water. The most significant linear relationship existed between the iAs concentration in drinking water and urinary iAs + MMA concentration. From these results, combined with the effects of seafood ingestion, the best biomarker of iAs exposure is urinary iAs + MMA concentration. PMID- 22048871 TI - (+)-Episesamin exerts anti-neoplastic effects in human hepatocellular carcinoma cell lines via suppression of nuclear factor-kappa B and inhibition of MMP-9. AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Treatment options, especially in advanced tumor stages, are still limited. Inhibition of signaling cascades involved in the pathogenesis of HCC - such as NF KB - offer a promising therapeutic approach. Aim of this study was to examine anti-neoplastic effects of (+)-episesamin which has been isolated from an anti fibrotic extract of Lindera obtusiloba on human HCC cells with particular interest in activation of NF-kappaB. The human HCC cell lines HepG2, Huh-7 and SK Hep1 were treated with (+)-episesamin. Beside measurement of proliferation, invasion and apoptosis, effects of (+)-episesamin on NF-kappaB-activity, VEGF secretion and enzymatic MMP-9 activity were determined. Anti-inflammatory effects were assessed by IL-6 ELISA using HCC cells and RAW264.7 macrophages. 10 MUM (+) episesamin reduced the proliferation of HCC cells by ~50%, suppressed invasion and induced apoptosis. DNA-binding ELISA experiments revealed that (+)-episesamin treated HCC cells showed a suppressed basal and TNFalpha-induced activation of NF kappaB and a subsequent suppression of TNFalpha- and LPS-induced IL-6 production. Further, (+)-episesamin exhibited inhibitory effects on the enzymatic activity of recombinant MMP-9 and the secretion of MMP-9 and VEGF by HCC cells into their supernatants. Our findings show that anti-neoplastic effects of (+)-episesamin are mediated via suppressed activation of NF-kappaB which entails a decreased release of pro-inflammatory IL-6. In addition, (+)-episesamin inhibits MMP-9, which is strongly expressed in invasive HCC, and the production of proangiogenic VEGF. We conclude that (+)-episesamin has the potential to be further explored as a complementary treatment for HCC. PMID- 22048872 TI - [Broncholithiasis, lithoptysis and broncho-oesophageal fistula]. AB - Broncho-oesophageal fistulas in broncholithiasis are extremely rare. Preceding lithoptysis is only seen infrequently. We report on a 68-year-old patient who complained of cough for more than 3 years. 5 months prior to admission he had hemoptysis and expectorated several greyish stones of up to 5 mm diameter. Endoscopy revealed a small excavation at the medial wall of the left main bronchus. Compared to a former CT, an actual CT scan of the thorax showed a small fistula between the oesophagus and the left main bronchus and revealed a missing calcification at this site. The patient underwent a left-sided thoracotomy with excision of the fistula, suture of the oesophagus and interponation of a flap of the M. latissimus dorsi. The demonstration of broncholith migration with CT scans before and after lithoptysis, the development of a left-sided fistula and its demonstration in the CT scan as well as endoscopically have not been reported in this combination before. PMID- 22048873 TI - [Pulmonary paraganglioma: case report and literature review]. AB - BACKGROUND: Pulmonary paraganglioma is a very rare condition with 40 cases reported in the literature. In the vast majority of cases the correct diagnosis could not be yielded preoperatively. CASE PRESENTATION: We report a case of paraganglioma of the lung. Computed tomographic scan showed a solitary pulmonary nodule. Diagnostic thoracotomy was performed and a tumor in the left lower lobe was resected. Frozen section evaluation showed an epithelial tumor with neuroendocrine differentiation and low grade features. Accordingly, lobectomy was performed. The study of the paraffin-embedded specimen yielded furthermore a neuroendocrine differentiated tumor, but mitotic figures were rare. Immunhistochemically the final diagnosis paraganglioma was made. CONCLUSION: In patients with pulmonary paraganglioma, the correct preoperative diagnosis is in general not available. Solitary pulmonary nodules or minor tumors of unknown histology are resected by wedge resection and sent to frozen section evaluation. Frozen section evaluation results in the diagnosis neuroendocrine tumor with more or less mitoses and mostly specified as carcinoid tumor. According to the literature biologic behaviour of carcinoid tumor and pulmonary paraganglioma is similar and thus the incorrect result of frozen section evaluation leads to a correct resection mode. If frozen section evaluation shows low grade features, surgical overtreatment may occur. PMID- 22048874 TI - [Costs of the influenza pandemic for the public health services - calculations based on the model of the metropolitan region Frankfurt am Main]. AB - The influenza pandemic of 2009 has been the biggest challenge to the public health services in post-war Germany. This study investigates the impact on the overall costs for the public health authorities of the metropolitan region Frankfurt am Main which arose in the context of the pandemic as well as the specific costs of the implementation and realisation of the vaccination campaign during the pandemic. In 2009 the incremental costs for the Health Protection Authority of the City of Frankfurt am Main for the prevention and logistics caused by this pandemic amounted to ? 223,537.91, whereas costs which could be directly attributed to the vaccination campaign (vaccine not included amounted to only a fraction thereof (? 45,401.48). The per-capita costs for vaccinated citizens were ? 10.66. These results clearly demonstrate the importance of adequate financial resources for the public health authorities to cope with infectious disease outbreaks and future pandemics. PMID- 22048875 TI - Expressed sexual assault legal context and victim culpability attributions. AB - Legal scholars have argued that laws have an expressive function, specifically that sexual assault laws may convey social-level messages that victims are culpable for crimes against them. In a university sample, we conducted the first experimental test of legal scholars' proposal, hypothesizing that legal messages specifically their clarity and effectiveness in conveying that sexual assault is a crime-affect victim culpability attributions. Results demonstrated that greater culpability was attributed to a victim of sexual assault within a context expressing unclear and ineffective sexual assault law than within a context clearly and effectively expressing that sexual assault is a crime. We also garnered empirical support for a mediation model, that is, negative affective reactions to a victim statistically accounted for the relationship between expressed legal context and victim culpability attributions. Implications for future psycholegal research and potential legal reforms are discussed. PMID- 22048876 TI - How do I treat "triple-negative" disease. AB - OPINION STATEMENT: Over the recent years, there has been an increasing recognition that triple-negative breast cancer constitutes a separate, albeit heterogeneous, entity arising from distinct oncogenic pathways. Despite its aggressive clinical behavior, triple-negative disease responds favorably to cytotoxic chemotherapy resulting in high response rates. Nonetheless, the relapse rates are high and, in the absence of targeted therapies to significantly alter its natural history, the prognosis can be poor. Most of the trials conducted in the past that led to the formulation of the current guidelines have indiscriminately lumped triple-negative disease with receptor-positive subtypes. Therefore, there are relatively scant data regarding how standard approaches specifically apply for triple-negative disease. By virtue of its chemosensitive nature and high probability of achieving a complete pathologic response, neoadjuvant chemotherapy in early-stage/operable and locally-advanced/inoperable triple-negative disease is highly recommended. The indications for adjuvant chemotherapy are the same as in receptor-positive tumors, although endocrine therapies or agents targeting Her2 signaling have no established role in triple negative disease. The optimal chemotherapy is not entirely clear; however, by virtue of their efficacy in breast cancer in general, anthracycline-containing regimens are the most widely used. The incorporation of taxanes in the regimen is supported by retrospective analyses. There is scant evidence to recommend any particular agent in the metastatic setting, although the combination of ixabepilone with capecitabine was shown to be active specifically in triple negative disease. Given the uncertainty in the optimal management of triple negative disease, the shortcomings of contemporary regimens, and the strong rationale of novel therapies, participation in clinical trials should be strongly considered at any stage of the disease. PMID- 22048877 TI - Optimization of a dual mechanism gastrofloatable and gastroadhesive delivery system for narrow absorption window drugs. AB - In order to overcome poor bioavailability of narrow absorption window drugs, a gastrosphere system comprising two mechanisms of gastric retention, namely buoyancy and gastroadhesion, has been investigated in this study employing poly(lactic-co-glycolic acid) (PLGA), polyacrylic acid (PAA), alginate, pectin, and a model drug metformin hydrochloride. Fifteen formulations were obtained using a Box-Behnken statistical design. The gastrosphere yield was above 80% in all cases; however, due to the high water solubility of metformin, drug entrapment efficacy was between 18% and 54%. Mean dissolution time and gastroadhesive strength were used as the formulation responses in order to optimize the formulation. Furthermore, the molecular mechanics force field simulations were performed to corroborate the experimental findings. Drug release profiles revealed three different release kinetics, namely, burst, first-order and zero-order release. Varying gastroadhesive results were obtained, and were highly sensitive to changes in polymer concentrations. FTIR revealed that strong bonds of PAA and PLGA were retained within the gastrosphere. Surface area and porosity analysis provided supporting evidence that the lyophilization process resulted in a significant increase in the porosity. Analysis of the surface morphology by SEM revealed that air pockets were spread over the entire surface of the gastrosphere, providing a visual proof of the high porosity and hence low density of the gastrosphere. The spatial disposition and energetic profile of the sterically constrained and geometrically optimized multi-polymeric complex of alginate, pectin, PAA, and PLGA corroborated the experimental results in terms of in vitro drug release and gastroadhesive strength of the fabricated gastrospheres. PMID- 22048878 TI - A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression. AB - This phase II trial was undertaken to evaluate the efficacy of TLN-4601 in patients with glioblastoma (GBM) at first progression. TLN-4601 inhibits the Ras MAPK signaling pathway, and in animal models crosses the blood-brain barrier and accumulates in implanted gliomas, possibly by binding specifically to the peripheral benzodiazepine receptor. A maximum of 40 patients with recurrent GBM were to be enrolled in this study. TLN-4601 was administered at a dose of 480 mg/m(2)/day by continuous intravenous (CIV) administration. Each 21-day cycle consisted of a 14-day CIV administration and a 7-day recovery period. Samples were obtained from all patients for pharmacokinetic evaluations (PK) and for Raf 1 and pERK biomarker assessment using immunohistochemistry and flow cytometry. Following enrollment of 20 patients, this study was terminated due to a lack of efficacy. Of 17 evaluable patients, 14 had MR scans performed after two cycles of TLN-4601. Of these 14 patients, three had stable disease and 11 had disease progression. Only three patients had MR scans performed after four cycles and all had evidence of radiographic progression. Serum PKs confirmed that patients were exposed to TLN-4601 at targeted drug levels. TLN-4601 was generally well tolerated although two patients discontinued treatment due to adverse events. Biomarker analysis did not show consistent changes. TLN-4601 infused via CIV at 480 mg/m(2)/day for 14 of 21 days is well tolerated by patients with progressive GBM. However, this agent is ineffective in progressive GBM when administered as monotherapy in this schedule. PMID- 22048880 TI - [Social inequalites, mental health and service provision]. PMID- 22048879 TI - Increased tryptophan transport in epileptogenic dysembryoplastic neuroepithelial tumors. AB - Dysembryoplastic neuroepithelial tumors (DNTs) are typically hypometabolic but can show increased amino acid uptake on positron emission tomography (PET). To better understand mechanisms of amino acid accumulation in epileptogenic DNTs, we combined quantitative alpha-[(11)C]methyl-L: -tryptophan (AMT) PET with tumor immunohistochemistry. Standardized uptake values (SUVs) of AMT and glucose were measured in 11 children with temporal lobe DNT. Additional quantification for AMT transport and metabolism was performed in 9 DNTs. Tumor specimens were immunostained for the L: -type amino acid transporter 1 (LAT1) and indoleamine 2,3-dioxygenase (IDO), a key enzyme of the immunomodulatory kynurenine pathway. All 11 tumors showed glucose hypometabolism, while mean AMT SUVs were higher than normal cortex in eight DNTs. Further quantification showed increased AMT transport in seven and high AMT metabolic rates in three DNTs. Two patients showing extratumoral cortical increases of AMT SUV had persistent seizures despite complete tumor resection. Resected DNTs showed moderate to strong LAT1 and mild to moderate IDO immunoreactivity, with the strongest expression in tumor vessels. These results indicate that accumulation of tryptophan in DNTs is driven by high amino acid transport, mediated by LAT1, which can provide the substrate for tumoral tryptophan metabolism through the kynurenine pathway, that can produce epileptogenic metabolites. Increased AMT uptake can extend to extratumoral cortex, and presence of such cortical regions may increase the likelihood of recurrent seizures following surgical excision of DNTs. PMID- 22048881 TI - [Unitary dementia]. PMID- 22048882 TI - [Diabetes mellitus and comorbid depression: economic findings from a systematic literature review]. AB - OBJECTIVE: To conduct a systematic literature review of cost-of-illness studies and economic evaluations for diabetic patients with comorbid depression. METHODS: Systematic literature search in PubMed and NHS EED in March 2011, complemented by a bibliographic search within all eligible articles. RESULTS: The search produced a total of 388 studies of which 16 were analysed in full text. Altogether, eleven studies were included into the review, all of which were conducted in the USA. The results from cost-of-illness studies (n = 8) indicate excess costs in between 35 % and 300 % for diabetics with comorbid depression, in comparison to those without depression. Three economic evaluations indicate that appropriate interventions can lead to improved health (i. e. more depression free days) at no extra cost. The results from two cost-effectiveness analyses indicate dominance (more depression free days and cost-savings compared to "usual care") for the evaluated interventions. CONCLUSIONS: Depressive symptoms are associated with increased health care costs in diabetic patients. Part of these excess costs can be attributed to the treatment of diabetes. Appropriate interventions aimed at depression treatment can increase time free of depression at no greater cost than usual care. PMID- 22048883 TI - [Psychiatry@home--establishing contact to a community mental health service via www]. AB - BACKGROUND: Psychiatric services increasingly use internet technologies to enhance and support usual therapies, which are based on direct personal contact. METHODS: An anonymous e-mail-request of a young girl obviously requiring psychiatric support and treatment is illustrated, characterized by the intention of the service to establish personal contact. CONCLUSIONS: Chances and limitations of psychiatric interventions using the internet are discussed. PMID- 22048884 TI - Efficacy, safety, and tolerability of a triple reuptake inhibitor GSK372475 in the treatment of patients with major depressive disorder: two randomized, placebo and active-controlled clinical trials. AB - GSK372475 is a triple reuptake inhibitor with approximately equipotent inhibition of serotonin, norepinephrine, and dopamine transporters. Two randomized, placebo- and active-controlled, double-blind studies examined the efficacy and safety of GSK372475 in outpatients (aged 18-64 years) with a diagnosis of major depressive episode associated with major depressive disorder (MDD). Patients were randomized 1:1:1 to placebo, GSK372475 (1-2 mg/d), or active control (Study 1: venlafaxine XR 150-225 mg/d; Study 2: paroxetine 20-30 mg/d). GSK372475 did not significantly differ from placebo on any of the key efficacy endpoints (six-item Bech scale, IDS-Clinician Rated, MADRS) in either study. Both active controls demonstrated significant antidepressant activity compared with placebo on both primary and secondary endpoints. The most common adverse effects (AEs) with GSK372475 were dry mouth, headache, insomnia, and nausea. AEs were more frequent for GSK372475 versus placebo for sleep, anxiety-related, gastrointestinal, and tachycardia events. Increases in mean change from baseline in heart rate and sitting blood pressure were greater for GSK372475 than observed for either placebo or active control groups. Completion rates were lower for GSK372475 (49%, 58%) compared with placebo (67%, 74%), venlafaxine XR (63%), or paroxetine (77%). GSK372475 was neither efficacious nor well tolerated in patients with MDD in two 10-week studies. PMID- 22048885 TI - Effects of lycopene and proanthocyanidins on hepatotoxicity induced by mercuric chloride in rats. AB - To evaluate the protective potential of lycopene (Lyc) and proanthocyanidins (PCs) against mercuric chloride (HgCl(2))-induced hepatotoxicity, the study focused on the mechanism of oxidative stress. Firstly, the rats were subcutaneously (s.c.) injected with 0, 2.2, 4.4, and 8.8 MUmol/kg HgCl(2). Additionally, 40 mg/kg Lyc and 450 mg/kg PCs were given to the rats intragastrically (i.g.) before exposure to 8.8 MUmol/kg HgCl(2). Then, body weight, liver weight coefficient, mercury (Hg) contents, histological feature, ultrastructure, apoptosis, reactive oxygen species (ROS), glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver were measured. Lactate dehydrogenase (LDH) and alanine transaminase (ALT) in serum were determined. After exposure to different concentrations of HgCl(2), it was found that Hg contents, pathological and ultrastructure injury, activities of LDH and ALT, apoptosis, and levels of ROS, GSH, and MDA increased and the activities of SOD and GSH-Px decreased in a concentration-dependent manner. Further investigation found that pretreatment with Lyc and PCs inhibited ROS production, protected antioxidant enzymes, and reversed hepatotoxicity. We concluded that Lyc and PCs had hepatoprotective effects on HgCl(2)-induced toxicity by antagonizing oxidative stress in rat liver. PMID- 22048886 TI - Ether-a-go-go 1 (Eag1) potassium channel expression in dopaminergic neurons of basal ganglia is modulated by 6-hydroxydopamine lesion. AB - The ether a go-go (Eag) gene encodes the voltage-gated potassium (K(+)) ion channel Kv10.1, whose function still remains unknown. As dopamine may directly affect K(+) channels, we evaluated whether a nigrostriatal dopaminergic lesion induced by the neurotoxin 6-hydroxydopamine (6-OHDA) would alter Eag1-K(+) channel expression in the rat basal ganglia and related brain regions. Male Wistar rats received a microinjection of either saline or 6-OHDA (unilaterally) into the medial forebrain bundle. The extent of the dopaminergic lesion induced by 6-OHDA was evaluated by apomorphine-induced rotational behavior and by tyrosine hydroxylase (TH) immunoreactivity. The 6-OHDA microinjection caused a partial or complete lesion of dopaminergic cells, as well as a reduction of Eag1+ cells in a manner proportional to the extent of the lesion. In addition, we observed a decrease in TH immunoreactivity in the ipsilateral striatum. In conclusion, the expression of the Eag1-K(+)-channel throughout the nigrostriatal pathway in the rat brain, its co-localization with dopaminergic cells and its reduction mirroring the extent of the lesion highlight a physiological circuitry where the functional role of this channel can be investigated. The Eag1-K(+) channel expression in dopaminergic cells suggests that these channels are part of the diversified group of ion channels that generate and maintain the electrophysiological activity pattern of dopaminergic midbrain neurons. PMID- 22048887 TI - Treatment of progressive brain stem glioma with bevacizumab: radiological, metabolic and histopathological aspects. PMID- 22048888 TI - Comparative screening of K-ras mutations in colorectal cancer and lung cancer patients using a novel real-time PCR with ADx-K-ras kit and Sanger DNA sequencing. AB - We determined frequency/types of K-ras mutations in colorectal/lung cancer. ADx-K ras kit (real-time/double-loop probe PCR) was used to detect somatic tumor gene mutations compared with Sanger DNA sequencing using 583 colorectal and 244 lung cancer paraffin-embedded clinical samples. Genomic DNA was used in both methods; mutation rates at codons 12/13 and frequency of each mutation were detected and compared. The data show that 91.4% colorectal and 59.0% lung carcinoma samples were detected conclusively by DNA sequencing, whereas 100% colorectal and lung samples were detected by ADx-K-ras kit. K-ras gene mutations were detected in 32.9-27.4% colorectal samples using kit and sequencing methods, respectively. Whereas 10.6-8.3% lung cancer samples were positively detected by kit and sequencing methods, respectively. Notably, 172/677 showed mutations and 467/677 showed wild type by both methods; 38 samples showed mutations with kit but wild type with sequencing. Mutations in colorectal samples were as follows: GGT -> GAT/codon-12 (35.1%); GGC -> GAC/codon-13 (26.6%); GGT -> GTT/codon-12 (18.2%); and GGT -> GCT/codon-12 (1.6%). Mutations in lung samples were as follows: GGT > GTT/codon-12 (40.9%) and GGT > GCT/codon-12 (4.5%). In conclusion, K-ras mutations involved 32.2% colorectal and 10.6% lung samples among this cohort. ADx K-ras real-time PCR showed higher detection rates (P < 0.05). The kit method has good clinical applicability as it is simple, fast, less prone to contamination and hence can be used effectively and reliably for clinical screening of somatic tumor gene mutations. PMID- 22048889 TI - Reversal of height dimorphism promotes pollen and seed dispersal in a wind pollinated dioecious plant. AB - Variation in the timing of reproductive functions in dioecious organisms may result in adaptive changes in the direction of sexual dimorphism during the breeding season. For plants in which both pollen and seeds are wind-dispersed, it may be advantageous for male plants to be taller when pollen is dispersed and female plants to be taller when seeds are dispersed. We examined the dynamics of height dimorphism in Rumex hastatulus, an annual, wind-pollinated, dioecious plant from the southern USA. A field survey of seven populations indicated that females were significantly taller than males at seed maturity. However, a glasshouse experiment revealed a more complex pattern of height growth during the life cycle. No dimorphism was evident prior to reproduction for six of seven populations, but at flowering, males were significantly taller than females in all populations. This pattern was reversed at reproductive maturity, consistent with field observations. Males flowered later than females and the degree of height dimorphism was greater in populations with a later onset of male flowering. We discuss the potential adaptive significance of temporal changes in height dimorphism for pollen and seed dispersal, and how this may be optimized for the contrasting reproductive functions of the sexes. PMID- 22048890 TI - Eurasian jays (Garrulus glandarius) overcome their current desires to anticipate two distinct future needs and plan for them appropriately. AB - Western scrub-jays (Aphelocoma californica) have been shown to overcome present satiety to cache food they will desire in the future. Here, we show that another corvid, the Eurasian jay (Garrulus glandarius), can distinguish between two distinct future desires and plan for each appropriately, despite experiencing a conflicting current motivation. We argue that these data address the criticisms of previous work, and suggest a way in which associative learning processes and future-oriented cognition may combine to allow prospective behaviour. PMID- 22048891 TI - Ranavirus: past, present and future. AB - Emerging infectious diseases are a significant threat to global biodiversity. While historically overlooked, a group of iridoviruses in the genus Ranavirus has been responsible for die-offs in captive and wild amphibian, reptile and fish populations around the globe over the past two decades. In order to share contemporary information on ranaviruses and identify critical research directions, the First International Symposium on Ranaviruses was held in July 2011 in Minneapolis, MN, USA. Twenty-three scientists and veterinarians from nine countries examined the ecology and evolution of ranavirus-host interactions, potential reservoirs, transmission dynamics, as well as immunological and histopathological responses to infection. In addition, speakers discussed possible mechanisms for die-offs, and conservation strategies to control outbreaks. PMID- 22048892 TI - Challenges in the conservation and sustainable use of genetic resources. AB - The meeting on 'Genetic Resources in the Face of New Environmental, Economic and Social Challenges' held in Montpellier (France) from 20-22 September 2011 brought together about 200 participants active in research and management of the genetic diversity of plant, animal, fungal and microbial species. Attendees had the rare opportunity to hear about agronomy, botany, microbiology, mycology, the social sciences and zoology in the same conference. The research teams presented the results of about 50 projects funded by the French Foundation for Research on Biodiversity to preserve genetic diversity carried out in Africa, Asia, Europe and the Americas. These projects aimed to better understand and manage genetic resources in a rapidly changing world (e.g. structural changes in the agricultural industry, the need for climate change mitigation and adaptation, the challenge of achieving food security despite the growing world population and changing dietary habits, the opportunities provided by the many new molecular biology tools, the problems caused by widespread scientific budget cuts). The meeting also hosted some roundtables open to all participants which provided a forum to establish a much needed dialogue between policy-makers, managers and researchers. PMID- 22048893 TI - Climate change experiments in temperate grasslands: synthesis and future directions. AB - The immediate need to understand the complex responses of grasslands to climate change, to ensure food supplies and to mitigate future climate change through carbon sequestration, necessitate a global, synthesized approach. Numerous manipulative experiments have altered temperature or precipitation, often in conjunction with other interacting factors such as grazing, to understand potential effects of climate change on the ecological integrity of temperate grasslands and understand the mechanisms of change. Although the different ways in which temperature and precipitation may change to effect grasslands were well represented, variability in methodology limited generalizations. Results from these experiments were also largely mixed and complex; thus, a broad understanding of temperate grassland responses to these factors remains elusive. A collaboration based on a set of globally dispersed, inexpensive experiments with consistent methodology would provide the data needed to better understand responses of temperate grassland to climate change. PMID- 22048895 TI - Detection of two QTL on chicken chromosome 14 for keyhole lymphet haemocyanin. AB - A keyhole lymphet haemocyanin is an antigen which triggers Th1 type of immune response. A QTL for a primary immune response towards keyhole lymphet haemocyanin has been detected on chicken chromosome 14 in three populations. The results from the most recent population were inconsistent and varied depending on the applied QTL detection model. The major goal of the current study was the reanalysis of this data using a 2 QTL model. Additionally, in order to provide more accurate estimates of QTL effects and positions, epistasis between the QTL was considered as a potential important contributor to quantitative traits. Four statistical models were assumed: M1: A model assuming marginal additive effects of two QTL; M2: A model assuming marginal and epistatic additive effects of two QTL; M3: A model assuming marginal additive and dominance effects of two QTL; M4: A model assuming marginal additive and dominance effects of two QTL and all possible pairwise epistases. Two QTL with significant additive and dominance effects were detected on chicken chromosome 14 using model M3. One QTL was detected at 63 cM between MCW0123 and ROS0005, another at 76 cM between ROS0005 and MCW0225/NTN2Lsts1 (FDR = 0.0051). Modelling only additive effects resulted in a significantly worse fit. On the other hand, including epistatic effects did not improve fit significantly. The current study confirms previous reports of the QTL location on GGA14. A notable finding of this study is recognition of two closely related QTL for a keyhole lymphet haemocyanin response at the distal part of chicken chromosome 14. PMID- 22048896 TI - FGFR2 mutation confers a less drastic gain of function in mesenchymal stem cells than in fibroblasts. AB - Gain-of-function mutations in FGFR2 cause Apert syndrome (AS), a disease characterized by craniosynostosis and limb bone defects both due to abnormalities in bone differentiation and remodeling. Although the periosteum is an important cell source for bone remodeling, its role in craniosynostosis remains poorly characterized. We hypothesized that periosteal mesenchymal stem cells (MSCs) and fibroblasts from AS patients have abnormal cell phenotypes that contribute to the recurrent fusion of the coronal sutures. MSCs and fibroblasts were obtained from the periostea of 3 AS patients (S252W) and 3 control individuals (WT). We evaluated the proliferation, migration, and osteogenic differentiation of these cells. Interestingly, S252W mutation had opposite effects on different cell types: S252W MSCs proliferated less than WT MSCs, while S252W fibroblasts proliferated more than WT fibroblasts. Under restrictive media conditions, only S252W fibroblasts showed enhanced migration. The presence of S252W mutation increased in vitro and in vivo osteogenic differentiation in both studied cell types, though the difference compared to WT cells was more pronounced in S252W fibroblasts. This osteogenic differentiation was reversed through inhibition of JNK. We demonstrated that S252W fibroblasts can induce osteogenic differentiation in periosteal MSCs but not in MSCs from another tissue. MSCs and fibroblasts responded differently to the pathogenic effects of the FGFR2(S252W) mutation. We propose that cells from the periosteum have a more important role in the premature fusion of cranial sutures than previously thought and that molecules in JNK pathway are strong candidates for the treatment of AS patients. PMID- 22048897 TI - Developmental and functional nature of human iPSC derived motoneurons. PMID- 22048898 TI - How can cells sense the elasticity of a substrate? An analysis using a cell tensegrity model. AB - A eukaryotic cell attaches and spreads on substrates, whether it is the extracellular matrix naturally produced by the cell itself, or artificial materials, such as tissue-engineered scaffolds. Attachment and spreading require the cell to apply forces in the nN range to the substrate via adhesion sites, and these forces are balanced by the elastic response of the substrate. This mechanical interaction is one determinant of cell morphology and, ultimately, cell phenotype. In this paper we use a finite element model of a cell, with a tensegrity structure to model the cytoskeleton of actin filaments and microtubules, to explore the way cells sense the stiffness of the substrate and thereby adapt to it. To support the computational results, an analytical 1D model is developed for comparison. We find that (i) the tensegrity hypothesis of the cytoskeleton is sufficient to explain the matrix-elasticity sensing, (ii) cell sensitivity is not constant but has a bell-shaped distribution over the physiological matrix-elasticity range, and (iii) the position of the sensitivity peak over the matrix-elasticity range depends on the cytoskeletal structure and in particular on the F-actin organisation. Our model suggests that F-actin reorganisation observed in mesenchymal stem cells (MSCs) in response to change of matrix elasticity is a structural-remodelling process that shifts the sensitivity peak towards the new value of matrix elasticity. This finding discloses a potential regulatory role of scaffold stiffness for cell differentiation. PMID- 22048899 TI - A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells. AB - There is great interest in how bone marrow derived stem cells make fate decisions. Numerous studies have investigated the role of individual growth factors on mesenchymal stem cell differentiation, leading to protocols for cartilage, bone and adipose tissue. However, these protocols overlook the role of biomechanics on stem cell differentiation. There have been various studies that have applied mechanical stimulation to constructs containing mesenchymal stem cells, with varying degrees of success. One critical fate decision is that between cartilage and bone. Articular motion is a combination of compressive, tensile and shear deformations; therefore, one can presume that compression alone is unlikely to be a sufficient mechanical signal to generate a cartilage-like tissue in vitro. Within this study, we aimed to determine the role of shear on the fate of stem cell differentiation. Specifically, we investigated the potential enhancing effect of surface shear, superimposed on cyclic axial compression, on chondrogenic differentiation of human bone marrow-derived stem cells. Using a custom built loading device we applied compression, shear or a combination of both stimuli onto fibrin/polyurethane composites in which human mesenchymal stem cells were embedded, while no exogenous growth-factors were added to the culture medium. Both compression or shear alone was insufficient for the chondrogenic induction of human mesenchymal stem cells. However, the application of shear superimposed upon dynamic compression led to significant increases in chondrogenic gene expression. Histological analysis detected sulphated glycosaminoglycan and collagen II only in the compression and shear group. The results obtained may provide insight into post-operative care after cell therapy involving mesenchymal stromal cells. PMID- 22048900 TI - Collagen fibrillogenesis in the development of the annulus fibrosus of the intervertebral disc. AB - The annulus fibrosus of the intervertebral disc is a complex, radial-ply connective tissue consisting of concentric lamellae of oriented collagen. Whilst much is known of the structure of the mature annulus, less is known of how its complex collagenous architecture becomes established; an understanding of which could inform future repair/regenerative strategies. Here, using a rat disc developmental series, we describe events in the establishment of the collagenous framework of the annulus at light and electron microscopic levels and examine the involvement of class I and II small leucine rich proteoglycans (SLRPs) in the matrix assembly process. We show that a period of sustained, ordered matrix deposition follows the initial cellular differentiation/orientation phase within the foetal disc. Fibrillar matrix is deposited from recesses within the plasma membrane into compartments of interstitial space within the outer annulus - the orientation of the secreted collagen reflecting the initial cellular orientation of the laminae. Medially, we demonstrate the development of a reinforcing 'cage' of collagen fibre bundles around the foetal nucleus pulpous. This derives from the fusion of collagen bundles between presumptive end-plate and inner annulus. By birth, the distinct collagenous architectures are established and the disc undergoes considerable enlargement to maturity. We show that fibromodulin plays a prominent role in foetal development of the annulus and its attachment to vertebral bodies. With the exception of keratocan, the other SLRPs appear associated more with cartilage development within the vertebral column, but all become more prominent within the disc during its growth and differentiation. PMID- 22048901 TI - Peroxisomal Acyl-CoA oxidase 4 activity differs between Arabidopsis accessions. AB - In plants, peroxisomes are the primary site of fatty acid beta-oxidation. Following substrate activation, fatty acids are oxidized by Acyl-CoA Oxidase (ACX) enzymes. Arabidopsis has six ACX genes, although ACX6 is not expressed. Biochemical characterization has revealed that each ACX enzyme acts on specific chain-length targets, but in a partially overlapping manner, indicating a degree of functional redundancy. Genetic analysis of acx single and double mutants in the Columbia (Col-0) accession revealed only minor phenotypes, but an acx3acx4 double mutant from Wassileskija (Ws) is embryo lethal. In this study, we show that acx3acx4(Col) and acx1acx3acx4(Col) mutants are viable and that enzyme activity in these mutants is significantly reduced on a range of substrates compared to wild type. However, the triple mutant displays only minor defects in seed-storage mobilization, seedling development, and adult growth. Although the triple mutant is defective in the three most active and highly-expressed ACX proteins, increases in ACX2 expression may support partial beta-oxidation activity. Comparison of acx mutant alleles in the Col-0 and Ws accessions reveals independent phenotypes; the Ws acx4 mutant uniquely shows increased sensitivity to propionate, whereas the Col-0 acx4 allele has sucrose-dependent growth in the light. To dissect the issues between Col-0 and Ws, we generated mixed background mutants. Although alleles with the Col-0 acx4 mutant were viable, we were unable to isolate an acx3acx4 line using the Ws acx4 allele. Reducing ACX4 expression in several Arabidopsis backgrounds showed a split response, suggesting that the ACX4 gene and/or protein functions differently in Arabidopsis accessions. PMID- 22048903 TI - The Asilomar conference on fundamentals of atmospheric pressure ionization techniques, October 8-12, 2010. PMID- 22048902 TI - The impact of bacterial infection on mast cell degranulation. AB - In developed countries, the prevalence of allergy is on the rise. Although the causes are unknown, it seems that (1) the disappearance of microbiota may play a role in the increase of allergies and (2) exposure to bacterial infections during childhood decreases the incidence of allergies. Although several cell types are involved in the development of allergy, mast cells play a major role in orchestrating inflammation. Upon activation, mast cell secretory granules fuse with the plasma membrane, resulting in the release of a number of inflammatory mediators. In addition to allergy, mast cells contribute to the innate immune response against a variety of bacteria. This is accomplished through the secretion of cytokines and other soluble mediators. Interestingly, there is growing evidence that mast cells exposed to bacteria down-regulate degranulation in response to IgE/Allergen stimulation. This inhibitory effect seems to require direct contact between bacteria and mast cells, but the intracellular mechanism by which bacterial contact suppresses allergic responses is unknown. Here, we review different aspects of mast cell physiology and discuss hypotheses as to how bacteria may influence mast cell degranulation. PMID- 22048904 TI - Ion yields for some salts in MALDI: mechanism for the gas-phase ion formation from preformed ions. AB - Preformed ion emission is the main assumption in one of the prevailing theories for peptide and protein ion formation in matrix-assisted laser desorption ionization (MALDI). Since salts are in preformed ion forms in the matrix-analyte mixture, they are ideal systems to study the characteristics of preformed ion emission. In this work, a reliable method to measure the ion yield (IY) in MALDI was developed and used for a solid salt benzyltriphenylphosphonium chloride and two room-temperature ionic liquids 1-butyl-3-methylimidazolium hexafluorophosphate and trihexyltetradecylphosphonium bis(2,4,4 trimethylpentyl)phosphinate. IY for the matrix (alpha-cyano-4-hydroxycinnamic acid, CHCA) was also measured. Taking 1 pmol salts in 25 nmol CHCA as examples, IYs for three salts were similar, (4-8) * 10(-4), and those for CHCA were (0.8 1.2) * 10(-7). Even though IYs for the salts and CHCA remained virtually constant at low analyte concentration, they decreased as the salt concentrations increased. Two models, Model 1 and Model 2, were proposed to explain low IYs for the salts and the concentration dependences. Both models are based on the fact that the ion-pair formation equilibrium is highly shifted toward the neutral ion pair. In Model 1, the gas-phase analyte cations were proposed to originate from the same cations in the solid that were dielectrically screened from counter anions by matrix neutrals. In Model 2, preformed ions were assumed to be released from the solid sample in the form of neutral ion pairs and the anions in the ion pairs were assumed to be eliminated via reactions with matrix-derived cations. PMID- 22048905 TI - Efficient structural characterization of poly(methacrylic acid) by activated electron photodetachment dissociation. AB - Characterization of end-groups in poly(methacrylic acid) (PMAA) was achieved using tandem mass spectrometry after activated-electron photodetachment dissociation (activated-EPD). In this technique, multiply deprotonated PMAA oligomers produced in the negative-ion mode of electrospray ionization were oxidized into radical anions upon electron photodetachment using a 220 nm laser wavelength, and further activated by collision. In contrast to conventional collision induced dissociation of negatively charged PMAA, which mainly consists of multiple dehydration steps, fragmentation of odd-electron species is shown to proceed via a radical-induced decarboxylation, followed by reactions involving backbone bond cleavages, giving rise to product ions containing one or the other oligomer termination. A single radical-induced mechanism accounts for the four main fragment series observed in MS/MS. The relative position of the radical and of the anionic center in distonic precursor ions determines the nature of the reaction products. Experiments performed using PMAA sodium salts allowed us to account for relative abundances of product ions in series obtained from PMAA, revealing that ion stability is ensured by hydrogen bonds within pairs of MAA units. PMID- 22048907 TI - [Serology of viral hepatitis]. PMID- 22048906 TI - Effects of walnuts (Juglans regia) on learning and memory functions. AB - Walnut has been regarded as a health food that is delicious and nutritious. Both preventive and therapeutic effects of walnut are well documented. Walnuts are rich in omega-3 fatty acids that are reported to have beneficial effects on brain function. The present work was designed to evaluate the effects of walnuts on learning and memory in male rats. The effect of oral intake of walnut was also monitored on food intake. Walnut was given orally to rats for a period of 28 days. Memory function in rats was assessed by elevated plus maze (EPM) and radial arm maze (RAM). A significant improvement in learning and memory of walnut treated rats compared to controls was observed. Walnut treated rats also exhibited a significant decrease in food intake while the change in growth rate (in terms of percentage) remained comparable between the two groups. Analysis of brain monoamines exhibited enhanced serotonergic levels in rat brain following oral intake of walnuts. The findings suggest that walnut may exert its hypophagic and nootropic actions via an enhancement of brain 5-HT metabolism. PMID- 22048909 TI - [Diabetes/insulin - 3 contributions from 1924 and comment from the current viewpoint]. PMID- 22048910 TI - [A smoking cessation intervention in the Swiss Armed Forces]. AB - Smoking is a major health risk in young adults. We undertook a study in young Swiss military recruits to determine the impact of intensive training and of help offered on smoking cessation during Basic Military Training (BMT). A questionnaire including questions according to their smoking status, sporting activities and, alcohol use was administered to 999 conscripts at beginning and at the end of the BMT. The results were compared to a control group of BMT schools where no such intervention took place. The study shows that the prevalence of smokers in the intervention group decreased (start BMT 31.9%, end BMT 25.5%; p = 0.021), while the prevalence of smokers increased in the control group (start BMT 26.4%, end BMT 32.6%; p = 0.038). A motivation to serve in the armed forces, as well as the willingness to stop smoking in the next month were the factors associated with a subsequent cessation of smoking during BMT. A smoke stop intervention during BMT is viable and can lead to a decrease in the prevalence of smoking at the end of BMT. PMID- 22048911 TI - [Renal denervation a new treatment option in resistant arterial hypertension]. AB - Resistant hypertension is defined as blood pressure that remains above therapeutic goal despite the use of 3 antihypertensive drugs including a diuretic. After exclusion of secondary causes and medical in compliance, the estimated prevalence of resistant arterial hypertension ranges from 4% to 19% in hypertensive patients. Treatment requires a multimodal therapeutic approach. Hyperactivation of the sympathetic nervous system plays a key role in the genesis of hypertension. Targeting renal sympathetic nerves, percutaneous catheter-based renal denervation is a new therapeutic option for the treatment of resistant arterial hypertension in selected drug resistant patients. PMID- 22048912 TI - [Does cannabis use lead to schizophrenia?]. AB - There is a high comorbidity between cannabis use and schizophrenia. Several factors contribute to this comorbidity: secondary development of addiction, cannabis-related induction of psychosis and shared neurobiological alterations. Meanwhile, there is evidence that cannabis use is associated with an increased risk of schizophrenia. Prospective epidemiological studies have shown that a frequent cannabis use doubles the risk for schizophrenia. Interestingly, schizophrenic patients with comorbid cannabis use often show significantly better performances in neuropsychological tests than patients without cannabis use. This is nevertheless not due to a positive effect of cannabis, but a sign of cannabis related psychosis induction in subjects with a higher level of function and less cognitive impairment. Whether cannabis use leads to schizophrenia is determined by the individual vulnerability. PMID- 22048913 TI - [Osgood-Schlatter disease]. PMID- 22048914 TI - [Rare cause of acute neck pain]. AB - The acute calcific tendinitis of the longus colli muscle is a rare inflammatory process of the prevertebral muscles. The clinical picture includes acute neck pain, limited range of motion of the cervical spine with stiffness and odynophagia. The laboratory findings demonstrate inflammatory signs. The incidence of the disease peaks between the third and sixth decade. The knowledge of the characteristic radiologic findings and the self-limiting course prevents the patient from needless medical and surgical interventions. PMID- 22048915 TI - [Not Available]. PMID- 22048916 TI - [Not Available]. PMID- 22048920 TI - Increased expression of calcium/calmodulin-dependent protein kinase type II subunit delta after rat traumatic brain injury. AB - Many cellular responses to Ca(2+) signals are mediated by Ca(2+)/calmodulin dependent enzymes, among which is the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). CaMKII was originally described in rat brain tissue. In rat brain, four different subunits of the kinase have been identified: alpha, beta, gamma, and delta. This study aims to investigate changes of CaMKIIdelta after traumatic brain injury and its possible role. Rat traumatic brain injury (TBI) model was established by controlled cortical injury system. In the present study, we mainly investigated the expression and cellular localization of CaMKIIdelta after traumatic brain injury. Western blot analysis revealed that CaMKIIdelta was present in normal rat brain cortex. It gradually increased, reached a peak at the third day after TBI, and then decreased. Importantly, more CaMKIIdelta was colocalized with neuron. In addition, Western blot detection showed that the third day postinjury was also the apoptosis peak indicated by the elevated expression of caspase-3.Importantly, immunohistochemistry analysis revealed that injury-induced expression of CaMKIIdelta was colabeled by caspase-3 (apoptosis cells marker). Moreover, pretreatment with the CaMKII inhibitor (KN62) reduced the injury-induced activation of caspase-3. Noticeably, the CaMKII inhibitor KN 62 could reduce TBI-induced cell injury assessed with lesion volume and attenuate behavioral outcome evaluated by motor test. These data suggested that CaMKIIdelta may be implicated in the apoptosis of neuron and the recovery of neurological outcomes. However, the inherent mechanisms remained unknown. Further studies are needed to confirm the exact role of CaMKIIdelta after brain injury. PMID- 22048921 TI - Using multivariate statistical methods to assess the groundwater quality in an arsenic-contaminated area of Southwestern Taiwan. AB - Groundwater is a major water resource in Southwestern Taiwan; hence, long-term monitoring of water quality is essential. The study aims to assess the hydrochemical characteristics of water in the arsenic-contaminated aquifers of Choushui River alluvial fan and Chianan Plain, Taiwan using multivariate statistical methods, namely, factor analysis (FA), cluster analysis (CA), and discriminant analysis (DA). Factor analysis is applied to reveal the processes controlling the hydrochemistry of groundwater. Cluster analysis is applied to spatially categorize the collected water samples based on the water quality. Discriminant analysis is then applied to elucidate key parameters associated with the occurrence of elevated As concentration (>10 MUg L(-1)) in groundwater. Major water types are characterized as Na-Ca-Cl and Na-Mg-Cl in the Choushui River alluvial fan and Chianan Plain, respectively. Inorganic species of arsenic (As), particularly As(III), prevail in these two groundwater catchments, and their levels are higher in the Chianan Plain than in the Choushui River alluvial fan. Through FA, three factors, namely, the degree of salination, As reduction, and iron (Fe) reduction, are determined and denoted irrespective of some differences between the factorial compositions. Spatial distribution patterns of factors As reduction and Fe reduction imply that the redox zonation is delineated by As- and Fe-dominance zones separately. The results of CA demonstrate that three main groups can be properly explained by the factors extracted via FA. Three- (Fe(2+), Fe(3+), and NH (4) (+) ) and four-parameters (Fe(2+), Fe(3+), NH (4) (+) , and Ca(2+)) derived from discriminant analysis for Choushui River alluvial fan and Chianan Plain are elucidated as key parameters affecting the distribution of As contained groundwater. The analytical results indicate that the reductive dissolution of Fe minerals is prerequisite for the mobilization of As, whereas the shift of redox condition from Fe- to As-reducing leads to the accumulation of dissolved As in this area. PMID- 22048922 TI - Statistical source identification of major and trace elements in groundwater downward the tailings dam of Miduk Copper Complex, Kerman, Iran. AB - Identifying the possible sources of potential harmful metals in groundwater systems plays a crucial role in evaluating the potential risks to residents and local plant cover. An attempt was made to define the origin of Al, Cd, Cu, Fe, Mo, Ni, and Pb in groundwater using multivariate statistic approaches [principal component analysis (PCA), hierarchical cluster analysis], and tailings sequential extraction by the method of Tessier et al. The concentrations of studied elements were measured in 42 samples collected from 15 stations surrounding and downward the tailings dam of Miduk Copper Complex, central province of Kerman, Iran. According to the PCA results, confirmed by cluster dendrogram and metal content measurement of tailings sequential extracts, two components accounting for nearly 73% of the total variance, controlled the heavy metal variability and classified the possible source of groundwater contamination into two categories: (1) upper seepage which controls the variability of Cd, Cu, Fe, Ni, and Pb and (2) toe seepage of tailings dump affecting on Mo and Al concentration in downstream groundwater. PMID- 22048923 TI - Application of Qual2Kw model as a tool for water quality management: Certima River as a case study. AB - Modelling can be a useful management tool because models allow the understanding of water body response to different pollution pressure scenarios which may help on the decision-making process and in prosecuting the Water Framework Directive objectives. This study aims to evaluate the usage of simple water quality models (Qual2Kw) applied to small river basins in order to better understand the response of a river to different loads of nitrogen and phosphorus. Qual2Kw model was applied to Certima River (Portugal), a small river that ends in a shallow lake called Pateira Fermentelos and represents a very important ecosystem to the local community. Along its pathway, Certima River has a significant enrichment in nutrients due to agriculture, livestock, domestic sewage and industrial effluents discharged into the river. In case of nitrogen, the highest loads are from domestic (44%) and diffuse (35%) sources. The main sources of phosphorous are domestic (46%), livestock (24%) and diffuse sources (20%). Certima River is strongly enriched with nutrients, and neither nitrogen nor phosphorous is limiting the algal growth. According to the criterion of Dodds et al. (Water Res, 32(5):1455-1462, 1998), the river is classified as eutrophic. By comparing in stream measurements with Qual2Kw simulations, it can be concluded that it would be necessary to decrease the actual pollutants loads of nitrogen and phosphorous 5 and 10 times, respectively, in order to change Certima River classification from eutrophic to mesotrophic. PMID- 22048924 TI - Karst aquifers on small islands--the island of Olib, Croatia. AB - Water supply is a major problem in the Adriatic islands, especially during the summer tourism season, and represents a limiting factor to the islands' further economic development. Much attention has been given to water supply solutions, primarily in terms of attempting to use the existing island water. Unfortunately, few islands have favourable hydrological conditions to accumulate significant quantities of surface water or groundwater. In the period from 2001 to 2004, investigations were conducted on many islands to define their own freshwater or partially brackish water resources since desalinisation technology could resolve a significant part of the water supply demand on small and distant islands. Due to the specificity and complexity of research in karst areas, the study was conducted in phases and included the geological and hydrogeological reconnaissance of the island, aimed at locating possible areas on the island where the necessary quantities of groundwater of adequate quality could be captured; a detailed hydrogeological mapping of the specified areas, geophysical investigation and test drilling; and, over several days, test pumping of the most promising borehole. One of the islands investigated was the island of Olib. The conducted surveys indicated that it is possible to pump about 3.5 L/s of groundwater from the karst aquifer of the island of Olib, which fully complies with the sanitary quality of drinking water. PMID- 22048925 TI - Heavy metal contaminations in the groundwater of Brahmaputra flood plain: an assessment of water quality in Barpeta District, Assam (India). AB - A study was conducted to evaluate the heavy metal contamination status of groundwater in Brahmaputra flood plain Barpeta District, Assam, India. The Brahmaputra River flows from the southern part of the district and its many tributaries flow from north to south. Cd, Fe, Mn, Pb, and Zn are estimated by using atomic absorption spectrometer, Perkin Elmer AA 200. The quantity of heavy metals in drinking water should be checked time to time; as heavy metal accumulation will cause numerous problems to living being. Forty groundwater samples were collected mainly from tube wells from the flood plain area. As there is very little information available about the heavy metal contamination status in the heavily populated study area, the present work will help to be acquainted with the suitability of groundwater for drinking applications as well as it will enhance the database. The concentration of iron exceeds the WHO recommended levels of 0.3 mg/L in about 80% of the samples, manganese values exceed 0.4 mg/L in about 22.5% of the samples, and lead values also exceed limit in 22.5% of the samples. Cd is reported in only four sampling locations and three of them exceed the WHO permissible limit (0.003 mg/L). Zinc concentrations were found to be within the prescribed WHO limits. Therefore, pressing awareness is needed for the betterment of water quality; for the sake of safe drinking water. Statistical analysis of the data was carried out using Special Package for Social Sciences (SPSS 16). PMID- 22048926 TI - The effect of inappropriate therapy on bacteremia by ESBL-producing bacteria. AB - OBJECTIVE: To describe the impact of empiric appropriate treatment and the risk factors associated with mortality in patients with bacteremia by E. coli, K. pneumoniae and P. mirabilis producing ESBL. METHODS: Data were reviewed in an 8 year retrospective study, and 128 bacteremias were found: 80 caused by E. coli (62.5%), 28 by K. pneumoniae (21.9%) and 20 by P. mirabilis (18.6%). RESULTS: The initial antibiotic treatment, administered within 72 h after the first positive blood culture, was appropriate with carbapenems or other antimicrobial agents with documented in vitro sensitivity in 53.8 and 16% of patients, respectively. The overall mortality 21 days after diagnosis was 17.2%, and it was 14.9 and 35.2% for patients adequately and inadequately treated, respectively. At univariate analysis the p value for mortality with and without appropriate treatment was 0.05, and significant differences were found only for previous positive blood cultures (p = 0.004) and presence of septic shock at diagnosis (p = 0.006). CONCLUSION: In this case series there was a high rate of initial appropriate empiric treatment, and only a marginal impact on mortality was found with regard to appropriate and inappropriate treatment. This report shows that the knowledge of ESBL-producing characteristics varies widely among the different case series for reasons that still have to be clarified. PMID- 22048927 TI - Preliminary results from a multidisciplinary university-based disease state management program focused on hypertension, hyperlipidemia, and diabetes. AB - OBJECTIVE: To describe the implementation and evaluation of a pilot multidisciplinary disease state management (DSM) program for diabetes, hypertension, and hyperlipidemia at a private, self-insured university (over 900 covered lives). METHODS: Enrollees met with a pharmacist, nurse, exercise physiologist, and students in these disciplines to improve clinical outcomes and fitness parameters. Clinical values, quality of life, patient knowledge of disease states, and patient satisfaction were assessed. RESULTS: Of the 20 patients in the pilot program, 17 completed 1 nursing and 2 pharmacist visits; 8 completed exercise physiology visits. At baseline, elevated blood pressure readings were observed in 64.7% (11 of 17) of patients, 20% of those with diabetes (1 of 5) had an elevated hemoglobin A1c value (HbA1c), and 82.4% (14 of 17) had a cholesterol value that was not at goal. At least 1 medication-related problem was observed in 16 patients (94.1%). At 3 months, all patients with diabetes achieved HbA1c levels at or below 7%, 4 patients attained blood pressure control, and 1 achieved normal cholesterol readings. Patients characterized participation in the program as valuable and convenient. CONCLUSIONS: Patients involved in the multidisciplinary DSM showed improved clinical outcomes after 3 months. Ongoing analysis of patient outcomes will determine the long-term effectiveness of the DSM. PMID- 22048928 TI - Neuroleptic-induced catatonia in two hospitalized patients. AB - PURPOSE: To report the cases of 2 hospitalized patients with chronic psychotic disorders who developed neuroleptic-induced catatonia (NIC), a catatonic extrapyramidal syndrome occurring after administration of a D2-receptor antagonist, and delineate the importance of prompt recognition and treatment. METHODS: Two patients with chronic psychotic disorders were admitted to the hospital for unstable medical conditions at which time their maintenance antipsychotic therapy was discontinued. Following administration of intravenous haloperidol, both patients developed catatonic and extrapyramidal signs. Both patients developed catatonia, rigidity, hyperthermia, leukocytosis, and elevations in creatine kinase. In both cases, the patients met the criteria for catatonia as evidenced by motoric immobility, stupor, mutism, and negativism. The syndrome resolved within a few days of stopping haloperidol and initiation of lorazepam. CONCLUSION: Neuroleptic-induced catatonia is underrecognized and can lead to potentially severe complications, although early recognition and treatment may prevent progression and complications. Previous reports do not underscore the importance of prompt recognition and treatment. PMID- 22048929 TI - Effectiveness and feasibility of pharmacist-led admission medication reconciliation for geriatric patients. AB - PURPOSE: Pharmacists have been shown to improve medication reconciliation at hospital admission. Limited resources may obligate pharmacy departments to target resources for medication reconciliation rather than extend services to the entire hospital. We conducted a prospective, randomized, nonblinded assessment of the effectiveness and feasibility of pharmacist-led admission medication reconciliation for geriatric patients. METHODS: Eighty-one geriatric patients were randomized 1:1 to receive medication reconciliation per current hospital practice or to pharmacist-led medication reconciliation at admission. The primary end point was medication profile appropriateness by pharmacist review at 48 hours postadmission. Secondary end points involved in determining the impact and feasibility of this program. RESULTS: Pharmacist-led medication was superior to standard hospital practice, with 48% of controls and 71% of intervention patients having appropriate medication profiles at 48 hours postadmission (P = .033). Pharmacists identified 116 discrepancies among 81 patients including predominantly omissions (41%) and a composite of wrong dose, route, or frequency (35%). Pharmacists spent a median 15 minutes per patient. CONCLUSION: Pharmacists improved admission medication reconciliation for geriatric patients. Pharmacists identified a significant number of discrepancies, including predominantly omissions and wrong dose, dosage form, or frequency. Pharmacists' contributions to medication reconciliation could yield substantial benefit to patient care. PMID- 22048930 TI - Case report: increased patient response to intramuscular haloperidol decanoate following a change in needle length. AB - INTRODUCTION: Intramuscular (IM) injection is a commonly used administration route for a variety of medications. Determining the optimum needle length for administration of IM formulations based on individual patient variables has not been extensively reported in patients receiving antipsychotic medication via IM administration. CASE REPORT: The patient, a 23-year-old African American female diagnosed with schizophrenia, was referred to a community-based treatment program following multiple inpatient admissions. At age 19, she began experiencing psychiatric symptoms that resulted in assault and incarceration. Treatment included separate trials of haloperidol and fluphenazine decanoate formulations with minimal success reported. At the time of evaluation, she was experiencing constant positive psychiatric symptomatology. Oral haloperidol was started. Haloperidol decanoate 150 mg by IM injection using a 1.5-inch needle was added and titrated to 350 mg IM over 11 months. Auditory hallucinations continued. Following refusal of a haloperidol level, the physician changed to a 2-inch needle for decanoate injections. Noticeable and continued slow improvement of her psychotic symptoms resulted. CONCLUSION: Needle length may be of new importance to practitioners. If anticipated results of IM antipsychotic medication administration are not realized, practitioners are urged to consider patient variables, notably the amount of adipose tissue in the administration area. PMID- 22048931 TI - Measuring fatigue in persons with multiple sclerosis: creating a crosswalk between the Modified Fatigue Impact Scale and the PROMIS Fatigue Short Form. AB - PURPOSE: To create cross-walk tables to associate scores for the Modified Fatigue Impact Scale (MFIS) with scores for the Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form (SF) in persons with Multiple Sclerosis (MS). METHODS: Cross-walk tables were created using equipercentile linking and based on data collected at one time point in a longitudinal study of persons with MS (N = 458). Validation of the tables was conducted using data collected at a subsequent time point (N = 444). Deviations between estimates and actual scores were compared across levels of fatigue. The impact of sample size on the precision of sample mean estimates was evaluated using bootstrapping. RESULTS: Correlations between deviations and fatigue level for the PROMIS Fatigue SF and MFIS were (-0.31) and (-0.30), respectively, indicating moderately greater deviations with lower fatigue scores. Estimated sample means were impacted by sample size. CONCLUSIONS: Cross-walk tables allow data from studies using different measures of fatigue to be combined to achieve larger sample sizes and to compare results. These tables are valid for group-level analyses with sample sizes of 150 or greater. PMID- 22048934 TI - [How much diagnostics is required in palliative care? Results from a representative survey and own experiences]. AB - BACKGROUND: Applying diagnostic techniques in palliative care (PC) requires a thorough balance between a physical, psychosocial (and financial) burden and its therapeutic relevance in far advanced diseases. The extent of diagnostic employment in PC, preferred techniques, application problems, its informative value and therapeutic significance still have to be described. METHODS: The Hospice and Palliative Care Evaluation (HOPE) 2007 collected data from the application of microbiological and imaging techniques in German PC institutions. Furthermore, 70 consecutive ultrasound scans in our PC unit have been retrospectively analyzed.In 691 PC patients (from a total of 3184 in HOPE), diagnostic techniques (DIA) were applied and documented. RESULTS: In-patients with DIA (86,1 %) and the HOPE collective showed a comparable age and duration of hospital stay. Microbiological techniques contributed to 26,1 % of all documented in-patient investigations, imaging techniques 69,1 %. Ultrasound was the preferred imaging technique on PC units (67,1 %), whilst radiography, CT or MRI scans were rather employed on oncology wards. Nuclear imaging was rarely documented. In 80,8 %, imaging diagnostics were considered relevant for further treatment decisions (in-patients only); transportation problems and pain during imaging were relevant obstacles. In our own patient cohort, ultrasound was applied rather for general prognostic purposes, less often resulting in immediate therapeutic actions. Transportation problems could be almost entirely avoided by using a mobile ultrasound device. CONCLUSION: DIA in PC are applied independently of age or duration of hospital stay; its therapeutic significance is considered to be high; procedural problems may be resolvable. Therefore, this survey might challenge the tradition of low technology in PC. PMID- 22048935 TI - [Preventive crisis management in general outpatient palliative care - prospectively cross-sectional study of General Practitioners in Eastern Bavaria]. AB - BACKGROUND: General out-patient palliative care (GOPC) must be integrated into the care of patients with life-limiting diseases. Aim of the study was to evaluate experiences of general practitioners concerning advance directives and palliative emergency sheets. METHODS: A self-provided survey was mailed to all general practitioners in Regensburg (cross-sectional study). Main outcome measures included responses regarding a palliative emergency sheet (PES) and a palliative emergency plan (PEP). The investigation period was four months. The analysis was performed using defined criteria (e. g. professional experience concerning palliative care patients, patients treated in nursing homes, patients with dementia). RESULTS: Sixty-nine questionnaires from 259 were analysed (response rate 27 %). 86 % of respondents named practical experience in the care of palliative patients, 46 % named theoretical knowledge in this field. 41 % and 40 % consider creating an advance directive for their practical work as important/very important (p = 0.004 concerning the treatment of more than five palliative care patients per three months). 52 % and 49 % regard a PES or a PEP to be relevant (PES median: 6.5, SD +/- 2.7; PEP median: 6.5 SD +/- 2.9; inter group analysis p < 0.05). 94 % of respondents name the general practitioner to be suitable for creating an advance directive. CONCLUSION: In Germany, GOPC in end of-life care is very important. This study shows that advance directives were declared as an important instrument for patients? autonomy. The sense of PES and PEP to ensure patients? autonomy, especially for acute emergency medical palliative care, must be better recognized. However, the increase in acceptance in the GOPC for such instruments must be disclosed. Further studies to investigate this problem are necessary. PMID- 22048932 TI - Implementing patient-reported outcomes assessment in clinical practice: a review of the options and considerations. AB - PURPOSE: While clinical care is frequently directed at making patients "feel better," patients' reports on their functioning and well-being (patient-reported outcomes [PROs]) are rarely collected in routine clinical practice. The International Society for Quality of Life Research (ISOQOL) has developed a User's Guide for Implementing Patient-Reported Outcomes Assessment in Clinical Practice. This paper summarizes the key issues from the User's Guide. METHODS: Using the literature, an ISOQOL team outlined considerations for using PROs in clinical practice; options for designing the intervention; and strengths, weaknesses, and resource requirements associated with each option. RESULTS: Implementing routine PRO assessment involves a number of methodological and practical decisions, including (1) identifying the goals for collecting PROs in clinical practice, (2) selecting the patients, setting, and timing of assessments, (3) determining which questionnaire(s) to use, (4) choosing a mode for administering and scoring the questionnaire, (5) designing processes for reporting results, (6) identifying aids to facilitate score interpretation, (7) developing strategies for responding to issues identified by the questionnaires, and (8) evaluating the impact of the PRO intervention on the practice. CONCLUSIONS: Integrating PROs in clinical practice has the potential to enhance patient-centered care. The online version of the User's Guide will be updated periodically. PMID- 22048936 TI - [Hemolytic anemias in adults]. AB - The erythrocyte lifespan in haemolytic anemia is shortened while erythropoesis is increased. Important labaratory findings are increased reticulocytes, LDH, indirect bilirubin and a decreased haptoglobin level. The most important diagnostic tool for further work up of hemolytic anemia is the direct antiglobulin test (DAT, Coombs test) to differentiate autoimmune hemolytic anemia (AIHA) from other causes. Another important group are fragmentation syndroms (hemolytic uremic syndrome and thrombotic thrombocytopenic purpura). In these forms of haemolytic anemia fragmented red blood cells can be found in the blood smear together with thrombocytopenia. A severe problem in paroxysmal nocturnal hematuria is the incidence of thrombosis. The following review describes the most important forms of hemolytic anemia in the adult and the diagnostic and therapeutic strategies. PMID- 22048937 TI - [25-year-old woman with headache and vomiting. Venous sinus thrombosis]. PMID- 22048938 TI - [Comparison of seasonal influenza vaccines: composition and properties]. AB - The influenza virus isolation in embryonated chicken eggs was possible early in 1930er years and allowed the influenza vaccine production. Most influenza vaccines were derived from this, but actually new virus cell culture methods are established. For better tolerability, influenza vaccines include only antigen proportions (split- and subunit vaccines) but with the disadvantage of minor vaccine efficacy. This was compared with the addition of adjuvants. Aluminium salts are used for many decades and still in use to enhance the effect of vaccines. New formulations are MF59, AS03, AS04 or toll- like receptor-agonists. Also virosomal formulations and "ISCOMs"(Immune Stimulating Complexes) are newly designed and compromises enhanced immune reactions. Actually a broad range of various influenza vaccines exist and are available for a very different group of patients (which depends on physical conditions, age, immune status or allergies). PMID- 22048939 TI - [Diagnosing and expertizing asbestos-induced occupational diseases]. AB - Due to latency periods that can last for decades, asbestos-related diseases show 18 years after the enforcement of the prohibition of asbestos application in Germany their highest numbers. In the centre of attention are asbestos-induced pleural fibroses, mesotheliomas, asbestoses, lung and laryngeal cancer. Diagnosing and expertizing these diseases causes difficulties, is hitherto non uniform and does frequently not correspond to the current medico-scientific expertise. This induced the German Respiratory Society as well as the German Society of Occupational and Environmental Medicine in cooperation with the German Society of Pathology, the German Radiology Society and the German Society of Otorhinolaryngology, Head and Cervical Surgery, to develop the above mentioned guideline during seven meetings moderated by AWMF. The required thorough diagnosis is based on the detailed recording of a qualified occupational history. Since the sole radiological and pathological-anatomical findings cannot sufficiently contribute to the causal relationship the occupational history recorded by a general physician and a specialist is of decisive importance. These physicians have to report suspected occupational diseases and to advise patients on social and medical questions. Frequently, problems occur if the recognition of an occupational disease is neglected due to a supposedly too low exposure or too few ferruginous bodies or low fibre concentrations in lung tissue. The new S2k directive summarizing the current medico-scientific knowledge is for this reason, for diagnoses and expert opinions as well as for the determination of a reduced capacity for work a very important source of information. PMID- 22048940 TI - Modeling and simulation of blood collection systems. AB - This paper addresses the modeling and simulation of blood collection systems in France for both fixed site and mobile blood collection with walk in whole blood donors and scheduled plasma and platelet donors. Petri net models are first proposed to precisely describe different blood collection processes, donor behaviors, their material/human resource requirements and relevant regulations. Petri net models are then enriched with quantitative modeling of donor arrivals, donor behaviors, activity times and resource capacity. Relevant performance indicators are defined. The resulting simulation models can be straightforwardly implemented with any simulation language. Numerical experiments are performed to show how the simulation models can be used to select, for different walk in donor arrival patterns, appropriate human resource planning and donor appointment strategies. PMID- 22048942 TI - Overexpression of AQP5 in cervical cancer: correlation with clinicopathological features and prognosis. AB - Accumulating evidence for overexpression of AQP5 in various types of human cancer suggests that it plays a key role in tumor biology. However, little is known about the function of AQP5 in human cervical cancer. This study was to investigate the expression profile of AQP5 in cervical cancer and its clinical significance. We detected the expression profile of AQP5 mRNA and protein in cervical cancer tissue and in corresponding normal tissue by qRT-PCR and western blotting. Immunohistochemistry was also used in the detection of AQP5 protein expression as well as the proliferation index of Ki-67. The clinicopathological implications of these proteins were analyzed statistically. Survival analysis was performed to assess prognostic significance. AQP5 mRNA was overexpressed in cervical cancer tissue when compared with corresponding normal tissue, so was AQP5 protein. Overexpression of AQP5 was significantly associated with lymph node involvement (P = 0.004). Overexpression of Ki-67 was associated with lymph node involvement (P = 0.018) and disease stage (P = 0.005). It was demonstrated a positive correlation between AQP5 and Ki-67 (r = 0.543, P < 0.01). Survival analysis revealed that overexpression of AQP5 and Ki-67 is associated with a poorer prognosis. These observations suggest that AQP5 plays a key role in cervical cancer and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in cervical cancer. Its evaluation with Ki-67 may provide reliable prognostic information on cervical cancer. PMID- 22048944 TI - Enzyme-sharing as a cause of multi-stationarity in signalling systems. AB - Multi-stationarity in biological systems is a mechanism of cellular decision making. In particular, signalling pathways regulated by protein phosphorylation display features that facilitate a variety of responses to different biological inputs. The features that lead to multi-stationarity are of particular interest to determine, as well as the stability, properties of the steady states. In this paper, we determine conditions for the emergence of multi-stationarity in small motifs without feedback that repeatedly occur in signalling pathways. We derive an explicit mathematical relationship phi between the concentration of a chemical species at steady state and a conserved quantity of the system such as the total amount of substrate available. We show that phi determines the number of steady states and provides a necessary condition for a steady state to be stable-that is, to be biologically attainable. Further, we identify characteristics of the motifs that lead to multi-stationarity, and extend the view that multi stationarity in signalling pathways arises from multi-site phosphorylation. Our approach relies on mass-action kinetics, and the conclusions are drawn in full generality without resorting to simulations or random generation of parameters. The approach is extensible to other systems. PMID- 22048943 TI - Prognostic significance of cyclooxygenase-2, epidermal growth factor receptor 1, and microvascular density in gastric cancer. AB - Gastric cancer remains a significant global health burden with poor treatment outcome. New treatment modalities that target inflammation, proliferation, and angiogenesis have been used in various cancers, including gastric cancer. We sought to study the pattern of expression of two important proteins, cyclooxygenase-2 and epidermal growth factor receptor, and their association with microvascular density, clinicopathological features, and survival in Arab Omani patients with gastric cancer. Formalin-fixed, paraffin-embedded tumors were studied by immunohistochemistry using monoclonal antibodies to cyclooxygenase-2, epidermal growth factor receptor, and CD34. The immunohistochemical results were correlated with clinicopathological features and survival. In our study population, we found a male/female ratio of 72:43, a median age of 59 years, stage III and IV incidence of 66.9%, and a median follow-up of 96 months. Positive expression rates of cyclooxygenase-2 and epidermal growth factor receptor were 89.6 and 23.5%, respectively. The median microvascular density value was 52.5. When this value was determined as the cut-off point, 50% of patients were found to have high microvascular density. Epidermal growth factor receptor over-expression correlated with high microvascular density values, advanced lymph node involvement (N3), and TNM stage presentation (III and IV). Similarly, lymph node involvement was associated with cyclooxygenase-2 over expression and high microvascular density. Univariate analysis showed that epidermal growth factor receptor over-expression, pathological T3 and T4 disease, and overall stage III and IV disease were adverse prognostic factors. On multivariate analysis using a Cox regression model, expression of epidermal growth factor receptor, and advanced TNM stage were significant adverse prognostic factors for overall survival. Expression of epidermal growth factor receptor in Arab Omani patients with gastric cancer correlates with aggressive tumor characteristics and is an independent prognostic factor. Further clinical studies are needed to evaluate the utility of epidermal growth factor receptor immunohistochemistry as a tool for gastric cancer treatment. PMID- 22048945 TI - Effect of oxidized low-density lipoprotein concentration polarization on human smooth muscle cells' proliferation, cycle, apoptosis and oxidized low-density lipoprotein uptake. AB - To clarify the effect of concentration polarization of oxidative modification of low-density lipoproteins (ox-LDLs) on human smooth muscle cells (SMCs), the proliferation, ox-LDL uptake and apoptosis with SMCs cultured on permeable (the permeable group) or non-permeable membranes (the non-permeable group) were analysed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, spectrofluorometry and flow cytometry using a parallel-plate flow chamber technique. The concentration polarization of ox-LDLs at the surface of the cultured cell monolayer was assessed by confocal laser microscopy. The results showed that concentration polarization of ox-LDLs could indeed occur at the cultured cell monolayer surface of the permeable group, leading to an enhanced wall concentration of ox-LDLs that was over 15 per cent higher than the bulk concentration of the perfusion solution at a pressure of 100 mmHg. When concentration of ox-LDLs in the perfusion solution was less than or equal to 100 ug ml(-1), SMCs' proliferation was induced, while cell apoptosis was induced when its concentration was above 150 ug ml(-1). The uptake of ox-LDLs by the cultured cells was significantly higher for the permeable group than for the non-permeable group. In addition, the ox-LDL-induced cell death and apoptosis were much more severe in the permeable group than that in the non-permeable group. Therefore, the experimental study suggests that concentration polarization of ox-LDLs plays an adverse role in the vascular system owing to its toxicity to vascular cells, in turn enhance ox-LDL infiltration into the arterial wall and accelerate SMC apoptosis. PMID- 22048947 TI - Applications of percolation theory to fungal spread with synergy. AB - There is increasing interest in the use of the percolation paradigm to analyse and predict the progress of disease spreading in spatially structured populations of animals and plants. The wider utility of the approach has been limited, however, by several restrictive assumptions, foremost of which is a strict requirement for simple nearest-neighbour transmission, in which the disease history of an individual is influenced only by that of its neighbours. In a recent paper, the percolation paradigm has been generalized to incorporate synergistic interactions in host infectivity and susceptibility, and the impact of these interactions on the invasive dynamics of an epidemic has been demonstrated. In the current paper, we elicit evidence that such synergistic interactions may underlie transmission dynamics in real-world systems by first formulating a model for the spread of a ubiquitous parasitic and saprotrophic fungus through replicated populations of nutrient sites and subsequently fitting and testing the model using data from experimental microcosms. Using Bayesian computational methods for model fitting, we demonstrate that synergistic interactions are necessary to explain the dynamics observed in the replicate experiments. The broader implications of this work in identifying disease-control strategies that deflect epidemics from invasive to non-invasive regimes are discussed. PMID- 22048946 TI - Determining elastic properties of skin by measuring surface waves from an impulse mechanical stimulus using phase-sensitive optical coherence tomography. AB - The mechanical properties of skin are important tissue parameters that are useful for understanding skin patho-physiology, which can aid disease diagnosis and treatment. This paper presents an innovative method that employs phase-sensitive spectral-domain optical coherence tomography (PhS-OCT) to characterize the biomechanical properties of skin by measuring surface waves induced by short impulses from a home-made shaker. Experiments are carried out on single and double-layer agar-agar phantoms, of different concentrations and thickness, and on in vivo human skin, at the forearm and the palm. For each experiment, the surface wave phase-velocity dispersion curves were calculated, from which the elasticity of each layer of the sample was determined. It is demonstrated that the experimental results agree well with previous work. This study provides a novel combination of PhS-OCT technology with a simple and an inexpensive mechanical impulse surface wave stimulation that can be used to non-invasively evaluate the mechanical properties of skin in vivo, and may offer potential use in clinical situations. PMID- 22048948 TI - Characterization and significance of ACE2 and Mas receptor in human colon adenocarcinoma. AB - INTRODUCTION: A new arm of the renin-angiotensin system (RAS) has been recently characterized; this includes angiotensin converting enzyme (ACE)2 and angiotensin (Ang)1-7, a heptapeptide acting through the Mas receptor (MasR). Recent studies show that Ang1-7 has an antiproliferative action on lung adenocarcinoma cells. The aim of this study was to characterize RAS expression in human colon adenocarcinoma and to investigate whether Ang1-7 exerts an antiproliferative effect on human colon adenocarcinoma cells. MATERIALS AND METHODS: Gene, protein expression and enzymatic activity of the main components of the RAS were determined on non-neoplastic colon mucosa as well as on the tumor mass and the mucosa taken 5 cm distant from it, both collected from patients with colon adenocarcinoma. Two different human colon cancer cell lines were treated with AngII and Ang1-7. RESULTS: The novel finding of this study was that MasR was significantly upregulated in colon adenocarcinoma compared with non-neoplastic colon mucosa, which showed little or no expression of it. ACE gene expression and enzymatic activity were also increased in the tumors. However, AngII and Ang1-7 did not have any pro-/antiproliferative effects in the cell lines studied. CONCLUSIONS: The data suggest that upregulation of the MasR could be used as a diagnostic marker of colon adenocarcinoma. PMID- 22048949 TI - [Expert consensus statement on interventional renal sympathetic denervation for hypertension treatment]. AB - This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure >= 160 mm Hg and >= 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24 hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate > 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time. PMID- 22048950 TI - Herpes encephalitis during natalizumab treatment in multiple sclerosis. AB - In this case report we describe the first non-fatal herpes simplex virus encephalitis (HSE) case with natalizumab for multiple sclerosis (MS). A 36-year old woman, previously treated with immunomodulatory and immunosuppressive drugs for MS, developed acute encephalitis after 6 monthly natalizumab perfusions. Brain imaging demonstrated suggestive bi-temporal lesions. Herpes simplex virus type-1 DNA was detected in cerebrospinal fluid. The patient improved gradually after a 21-day course of intravenous acyclovir, but neuropsychiatric changes remained 5 months later. Our non-fatal case of HSE and other reported cases of herpes infections provide evidence of an increased risk with natalizumab and point to the need for clinicians to maintain awareness. PMID- 22048951 TI - Physiological variation as a mechanism for developmental caste-biasing in a facultatively eusocial sweat bee. AB - Social castes of eusocial insects may have arisen through an evolutionary modification of an ancestral reproductive ground plan, such that some adults emerge from development physiologically primed to specialize on reproduction (queens) and others on maternal care expressed as allo-maternal behaviour (workers). This hypothesis predicts that variation in reproductive physiology should emerge from ontogeny and underlie division of labour. To test these predictions, we identified physiological links to division of labour in a facultatively eusocial sweat bee, Megalopta genalis. Queens are larger, have larger ovaries and have higher vitellogenin titres than workers. We then compared queens and workers with their solitary counterparts-solitary reproductive females and dispersing nest foundresses-to investigate physiological variation as a factor in caste evolution. Within dyads, body size and ovary development were the best predictors of behavioural class. Queens and dispersers are larger, with larger ovaries than their solitary counterparts. Finally, we raised bees in social isolation to investigate the influence of ontogeny on physiological variation. Body size and ovary development among isolated females were highly variable, and linked to differences in vitellogenin titres. As these are key physiological predictors of social caste, our results provide evidence for developmental caste-biasing in a facultatively eusocial bee. PMID- 22048952 TI - Parasitic infection and oxidative status are associated and vary with breeding activity in the Seychelles warbler. AB - Parasites can have detrimental effects on host fitness, and infection typically results in the stimulation of the immune system. While defending against infection, the immune system generates toxic oxidants; if these are not sufficiently counteracted by the antioxidant system, a state of oxidative stress can occur. Here, we investigated the relationship between parasitic infection using malarial infection as a model-and oxidative status in a natural population of the Seychelles warbler, while taking into account potentially interacting environmental covariates. We found that malaria is associated with increased susceptibility to oxidative stress, but this depends on the breeding stage: only during the energetically demanding provisioning stage did infected birds have higher oxidative stress susceptibility than non-infected birds. The imbalance in oxidative status was caused by a marked increase in oxidant levels observed only in infected birds during provisioning and by an overall reduction in antioxidant capacity observed in all birds across the breeding cycle. This finding implies that higher workload while dealing with an infection could aggravate oxidative repercussions. Malarial infection was not associated with body condition loss, suggesting that even when conditional effects are not directly visible, detrimental effects may still manifest themselves over the longer term through the oxidative consequences. PMID- 22048953 TI - Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones. AB - Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficiency in sea water is further demonstrated by the rapid paralysis of fish or crustacean larvae upon application of recombinant Nv1 into their medium. Analysis of other anemone species reveals that in Anthopleura elegantissima, Type I neurotoxins also appear in gland cells, whereas in the common species Anemonia viridis, Type I toxins are localized to both nematocytes and ectodermal gland cells. The nematocyte-based and gland cell-based envenomation mechanisms may reflect substantial differences in the ecology and feeding habits of sea anemone species. Overall, the immunolocalization of neurotoxins to gland cells changes the common view in the literature that sea anemone neurotoxins are produced and delivered only by stinging nematocytes, and raises the possibility that this toxin-secretion mechanism is an ancestral evolutionary state of the venom delivery machinery in sea anemones. PMID- 22048954 TI - The sophisticated visual system of a tiny Cambrian crustacean: analysis of a stalked fossil compound eye. AB - Fossilized compound eyes from the Cambrian, isolated and three-dimensionally preserved, provide remarkable insights into the lifestyle and habitat of their owners. The tiny stalked compound eyes described here probably possessed too few facets to form a proper image, but they represent a sophisticated system for detecting moving objects. The eyes are preserved as almost solid, mace-shaped blocks of phosphate, in which the original positions of the rhabdoms in one specimen are retained as deep cavities. Analysis of the optical axes reveals four visual areas, each with different properties in acuity of vision. They are surveyed by lenses directed forwards, laterally, backwards and inwards, respectively. The most intriguing of these is the putatively inwardly orientated zone, where the optical axes, like those orientated to the front, interfere with axes of the other eye of the contralateral side. The result is a three dimensional visual net that covers not only the front, but extends also far laterally to either side. Thus, a moving object could be perceived by a two dimensional coordinate (which is formed by two axes of those facets, one of the left and one of the right eye, which are orientated towards the moving object) in a wide three-dimensional space. This compound eye system enables small arthropods equipped with an eye of low acuity to estimate velocity, size or distance of possible food items efficiently. The eyes are interpreted as having been derived from individuals of the early crustacean Henningsmoenicaris scutula pointing to the existence of highly efficiently developed eyes in the early evolutionary lineage leading towards the modern Crustacea. PMID- 22048955 TI - Tangled in a sparse spider web: single origin of orb weavers and their spinning work unravelled by denser taxonomic sampling. AB - In order to study the tempo and the mode of spider orb web evolution and diversification, we conducted a phylogenetic analysis using six genetic markers along with a comprehensive taxon sample. The present analyses are the first to recover the monophyly of orb-weaving spiders based solely on DNA sequence data and an extensive taxon sample. We present the first dated orb weaver phylogeny. Our results suggest that orb weavers appeared by the Middle Triassic and underwent a rapid diversification during the end of the Triassic and Early Jurassic. By the second half of the Jurassic, most of the extant orb-weaving families and web designs were already present. The processes that may have given origin to this diversification of lineages and web architectures are discussed. A combination of biotic factors, such as key innovations in web design and silk composition, as well as abiotic environmental changes, may have played important roles in the diversification of orb weavers. Our analyses also show that increased taxon sampling density in both ingroups and outgroups greatly improves phylogenetic accuracy even when extensive data are missing. This effect is particularly important when addition of character data improves gene overlap. PMID- 22048956 TI - Bacterial recombination promotes the evolution of multi-drug-resistance in functionally diverse populations. AB - Bacterial recombination is believed to be a major factor explaining the prevalence of multi-drug-resistance (MDR) among pathogenic bacteria. Despite extensive evidence for exchange of resistance genes from retrospective sequence analyses, experimental evidence for the evolutionary benefits of bacterial recombination is scarce. We compared the evolution of MDR between populations of Acinetobacter baylyi in which we manipulated both the recombination rate and the initial diversity of strains with resistance to single drugs. In populations lacking recombination, the initial presence of multiple strains resistant to different antibiotics inhibits the evolution of MDR. However, in populations with recombination, the inhibitory effect of standing diversity is alleviated and MDR evolves rapidly. Moreover, only the presence of DNA harbouring resistance genes promotes the evolution of resistance, ruling out other proposed benefits for recombination. Together, these results provide direct evidence for the fitness benefits of bacterial recombination and show that this occurs by mitigation of functional interference between genotypes resistant to single antibiotics. Although analogous to previously described mechanisms of clonal interference among alternative beneficial mutations, our results actually highlight a different mechanism by which interactions among co-occurring strains determine the benefits of recombination for bacterial evolution. PMID- 22048957 TI - An alternative method of endotracheal intubation of common marmosets (Callithrix jacchus). AB - Endotracheal intubation was carried out in 11 common marmosets (Callithrix jacchus). A commercially available tilting stand and a Miller laryngoscope blade were used to visualize the larynx. Anaesthesia was induced with alphaxalone (10.6 +/- 1.6 mg/kg intramuscularly, followed by 3.2 +/- 1.2 mg/kg intravenously). The diameter of the proximal trachea easily fitted an endotracheal tube made from readily available material (a 12 G 'over the needle' catheter). Once the tip of the endotracheal tube was at the level of the vocal folds, the tube had to be gently rotated through a 180 degrees angle in order to pass through the larynx into the trachea. Assessment of the dimensions of the larynx and trachea, and comparison with external anatomical features of the animals (n = 10) showed that the length of the trachea could be predicted by multiplying the craniosacral length of the marmoset by a factor of 0.42. PMID- 22048958 TI - A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations. AB - We have identified a point mutation in Npc1 that creates a novel mouse model (Npc1(nmf164)) of Niemann-Pick type C1 (NPC) disease: a single nucleotide change (A to G at cDNA bp 3163) that results in an aspartate to glycine change at position 1005 (D1005G). This change is in the cysteine-rich luminal loop of the NPC1 protein and is highly similar to commonly occurring human mutations. Genetic and molecular biological analyses, including sequencing the Npc1(spm) allele and identifying a truncating mutation, confirm that the mutation in Npc1(nmf164) mice is distinct from those in other existing mouse models of NPC disease (Npc1(nih), Npc1(spm)). Analyses of lifespan, body and spleen weight, gait and other motor activities, as well as acoustic startle responses all reveal a more slowly developing phenotype in Npc1(nmf164) mutant mice than in mice with the null mutations (Npc1(nih), Npc1(spm)). Although Npc1 mRNA levels appear relatively normal, Npc1(nmf164) brain and liver display dramatic reductions in Npc1 protein, as well as abnormal cholesterol metabolism and altered glycolipid expression. Furthermore, histological analyses of liver, spleen, hippocampus, cortex and cerebellum reveal abnormal cholesterol accumulation, glial activation and Purkinje cell loss at a slower rate than in the Npc1(nih) mouse model. Magnetic resonance imaging studies also reveal significantly less demyelination/dysmyelination than in the null alleles. Thus, although prior mouse models may correspond to the severe infantile onset forms of NPC disease, Npc1(nmf164) mice offer many advantages as a model for the late-onset, more slowly progressing forms of NPC disease that comprise the large majority of human cases. PMID- 22048959 TI - Whirlin interacts with espin and modulates its actin-regulatory function: an insight into the mechanism of Usher syndrome type II. AB - Whirlin mutations cause retinal degeneration and hearing loss in Usher syndrome type II (USH2) and non-syndromic deafness, DFNB31. Its protein recruits other USH2 causative proteins to form a complex at the periciliary membrane complex in photoreceptors and the ankle link of the stereocilia in hair cells. However, the biological function of this USH2 protein complex is largely unknown. Using a yeast two-hybrid screen, we identified espin, an actin-binding/bundling protein involved in human deafness when defective, as a whirlin-interacting protein. The interaction between these two proteins was confirmed by their coimmunoprecipitation and colocalization in cultured cells. This interaction involves multiple domains of both proteins and only occurs when espin does not bind to actin. Espin was partially colocalized with whirlin in the retina and the inner ear. In whirlin knockout mice, espin expression changed significantly in these two tissues. Further studies found that whirlin increased the mobility of espin and actin at the actin bundles cross-linked by espin and, eventually, affected the dimension of these actin bundles. In whirlin knockout mice, the stereocilia were thickened in inner hair cells. We conclude that the interaction between whirlin and espin and the balance between their expressions are required to maintain the actin bundle network in photoreceptors and hair cells. Disruption of this actin bundle network contributes to the pathogenic mechanism of hearing loss and retinal degeneration caused by whirlin and espin mutations. Espin is a component of the USH2 protein complex and could be a candidate gene for Usher syndrome. PMID- 22048960 TI - Inhibition of GSK3beta improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome. AB - Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis and hippocampus-dependent learning and FMRP regulates the adult neural stem cell fate through the translational regulation of glycogen synthase kinase 3beta (GSK3beta), we investigated the effects of a GSK3beta inhibitor, SB216763, on Fmr1 knockout mice (Fmr1 KO). We found that the inhibition of GSK3beta could reverse the hippocampus-dependent learning deficits and rescue adult hippocampal neurogenesis at multiple stages in Fmr1 KO mice. Our results point to GSK3beta inhibition as a potential treatment for the learning deficits seen in FXS. PMID- 22048961 TI - Association of GTF2i in the Williams-Beuren syndrome critical region with autism spectrum disorders. AB - Duplications of 7q11.23, deleted in Williams-Beuren Syndrome, have been implicated in autism spectrum disorders (ASDs). A 1.5 Mb duplication was identified in one girl with severe expressive language deficits and anxiety among 1,142 ASD individuals screened for this duplication. Family-based association studies of Tag-SNPs in three genes (STX1A , CYLN2 and GTF2i) in two multiplex autism family cohorts revealed strong association of two GTF2i SNPs and their haplotype in Cohort 1 and the combined families. The risk alleles and haplotype were associated with severe problems in social interaction and excessive repetitive behaviors. Our findings suggest the GTF2i gene is important in the etiology of autism in individuals with this duplication and in non-duplication cases with severe social interaction problems and repetitive behaviors. PMID- 22048962 TI - The prevalence of autism spectrum disorders in toddlers: a population study of 2 year-old Swedish children. AB - Autism Spectrum Disorder (ASD) is more common than previously believed. ASD is increasingly diagnosed at very young ages. We report estimated ASD prevalence rates from a population study of 2-year-old children conducted in 2010 in Gothenburg, Sweden. Screening for ASD had been introduced at all child health centers at child age 21/2 years. All children with suspected ASD were referred for evaluation to one center, serving the whole city of Gothenburg. The prevalence for all 2-year-olds referred in 2010 and diagnosed with ASD was 0.80%. Corresponding rates for 2-year-olds referred to the center in 2000 and 2005 (when no population screening occurred) were 0.18 and 0.04%. Results suggest that early screening contributes to a large increase in diagnosed ASD cases. PMID- 22048963 TI - Primary adrenal angiosarcoma and functioning adrenocortical adenoma: an exceptional combined tumor. AB - CONTEXT: Primary adrenal angiosarcoma is an extremely rare neoplasm, as are combined tumors within a given adrenal lesion. CLINICAL PRESENTATION AND INTERVENTION: A 35-year-old man presented with hypokalemic hypertension leading to the discovery of a 6 cm diameter malignant-appearing right adrenal tumor. The lesion displayed marked (18)F-fluorodeoxyglucose uptake on positron emission tomography scanning. Endocrine investigations revealed secretion of both cortisol and aldosterone by the neoplasm. The entire right adrenal gland along with the periadrenal fat tissue was removed during laparoscopic surgery. RESULTS: Histological examination revealed two intermingled tumor cell proliferations, namely an angiosarcoma and an adrenocortical adenoma. An extensive post-operative search revealed no other primary tumor site, nor metastases. The lesion was then considered to be a primary adrenal angiosarcoma combined with a secreting adrenocortical adenoma. The patient received four cycles of chemotherapy (adriamycin/ifosfamide). At 2-year follow-up, he is alive and well, with no sign of relapse. CONCLUSION: To the best of our knowledge, this is the first case of an adrenal neoplasm combining a primary angiosarcoma and a functioning adrenocortical adenoma. PMID- 22048964 TI - Combined expression of BUB1B, DLGAP5, and PINK1 as predictors of poor outcome in adrenocortical tumors: validation in a Brazilian cohort of adult and pediatric patients. AB - BACKGROUND: A recent microarray study identified a set of genes whose combined expression patterns were predictive of poor outcome in a cohort of adult adrenocortical tumors (ACTs). The difference between the expression values measured by qRT-PCR of DLGAP5 and PINK1 genes was the best molecular predictor of recurrence and malignancy. Among the adrenocortical carcinomas, the combined expression of BUB1B and PINK1 genes was the most reliable predictor of overall survival. The prognostic and molecular heterogeneity of ACTs raises the need to study the applicability of these molecular markers in other cohorts. OBJECTIVE: To validate the combined expression of BUB1B, DLGAP5, and PINK1 as outcome predictor in ACTs from a Brazilian cohort of adult and pediatric patients. PATIENTS AND METHODS: BUB1B, DLGAP5, and PINK1 expression was assessed by quantitative PCR in 53 ACTs from 52 patients - 24 pediatric and 28 adults (one pediatric patient presented a bilateral asynchronous ACT). RESULTS: DLGAP5-PINK1 and BUB1B-PINK1 were strong predictors of disease-free survival and overall survival, respectively, among adult patients with ACT. In the pediatric cohort, these molecular predictors were only marginally associated with disease-free survival but not with overall survival. CONCLUSION: This study confirms the prognostic value of the combined expression of BUB1B, DLGAP5, and PINK1 genes in a Brazilian group of adult ACTs. Among pediatric ACTs, other molecular predictors of outcome are required. PMID- 22048965 TI - Association of glucocorticoid receptor polymorphism A3669G with decreased risk of developing diabetes in patients with Cushing's syndrome. AB - OBJECTIVE: Glucocorticoid receptor (GR) polymorphisms alter glucocorticoid (GC) sensitivity and have been associated with altered metabolic profiles. We evaluate the prevalence of the four GR (NR3C1) polymorphisms BclI, N363S, ER22/23EK, and A3669G in patients with Cushing's syndrome (CS) compared with healthy controls (HC) and we investigate their role in the development of metabolic abnormalities in patients with CS according to their hormonal profile. PATIENTS AND METHODS: Sixty-one patients with CS and 71 sex- and age-matched HC were genotyped. RESULTS: BclI variant was markedly higher in patients with CS compared with HC (62 vs 41%, P<0.05) while no significant differences were found among other polymorphisms. A very low frequency of N363S and the ER22/23EK was observed. In CS patients, despite the significantly increased levels of morning serum cortisol in BclI carriers compared with wild type no clinical or metabolic differences were found. In contrast, A3669G GR carriers showed a significantly reduced prevalence of type 2 diabetes mellitus compared with wild type (19 vs 68%, P=0.001) despite the higher levels of both serum morning (21.7+/-6 vs 27.3+/-8.6 MUg/dl, P=0.009) and midnight cortisol (18.8+/-5.8 vs 24.0+/-8.0 MUg/dl, P=0.01). The negative association between diabetes and A3669G GR polymorphism remained significant when data were adjusted for potential confounding factors. CONCLUSIONS: The A3669G polymorphism of the GR gene plays a protective role in patients with CS, attenuating the effects of GC excess on glucose metabolism as shown by their reduced risk of diabetes. PMID- 22048966 TI - Diagnosis of endocrine disease: limitations of the IGF1 generation test in children with short stature. AB - The IGF1 generation test (IGFGT) is often used during the assessment of suspected GH insensitivity (GHI). We report the results of a survey undertaken in 2010 to determine the use of IGFGT amongst members of the European Society for Paediatric Endocrinology to evaluate suspected GHI. The literature surrounding the usefulness and limitations of IGFGT are reviewed, and recommendations provided for its use. Of 112 paediatric endocrinologists from 30 countries who responded to the survey, 91 (81%) reported that they had used the IGFGT in the previous 2 years; >10 IGFGT protocols were used. The IGFGT impacted treatment decisions for 97% of the respondents and was a prerequisite for recombinant human IGF1 treatment for 45% of respondents. From a literature review, sensitivity of the IGFGT was evaluated as 77-91% in molecularly proven cases of GHI; specificity was <=97%, depending on the protocol. The positive predictive value of the IGFGT is likely to be low, as the frequency of normality is predictably higher than that of abnormality in GH signalling. Given the limitations of the IGFGT in the most severe cases of GHI syndrome (GHIS), the ability of the IGFGT to detect less severe GHIS is doubtful. In a pragmatic approach, the IGFGT may not be useful for the diagnosis of GHIS. PMID- 22048967 TI - Effects of teriparatide in postmenopausal women with osteoporosis pre-treated with bisphosphonates: 36-month results from the European Forsteo Observational Study. AB - OBJECTIVES: To describe fracture rates, back pain, and health-related quality of life (HRQoL) in postmenopausal women with osteoporosis and prior bisphosphonate therapy, treated with teriparatide for up to 18 months and followed up for a further 18 months. DESIGN: Prospective, multinational, and observational study. METHODS: Data on prior bisphosphonate use, clinical fractures, back pain visual analog scale (VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed using a repeated measures model. RESULTS: Of the 1581 enrolled patients with follow-up data, 1161 (73.4%) had a history of prior bisphosphonate use (median duration: 36 months). Of them, 169 (14.6%) sustained >=1 fracture during 36-month follow-up. Adjusted odds of fracture were significantly decreased at each 6-month interval compared with the first 6 months of teriparatide treatment: 37% decrease in the 12 to <18 months period during teriparatide treatment (P=0.03) and a 76% decrease in the 12- to 18-month period after teriparatide was discontinued (P<0.001). Significant reductions in back pain and improvement in HRQoL were observed. CONCLUSIONS: Postmenopausal women with severe osteoporosis previously treated with bisphosphonates had a significant reduction in the incidence of fractures compared with the first 6 months of therapy, a reduction in back pain and an improvement in HRQoL during up to 18 months of teriparatide treatment. These outcomes were still evident for at least 18 months after teriparatide was discontinued. The results should be interpreted in the context of an uncontrolled, observational study in a routine clinical setting. PMID- 22048968 TI - Association of hypogonadism with vitamin D status: the European Male Ageing Study. AB - OBJECTIVE: Interrelationships between hormones of the hypothalamic-pituitary testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men. DESIGN AND METHODS: Cross-sectional survey of 3369 community-dwelling men aged 40-79 years in eight European centres. Testosterone (T), oestradiol (E(2)) and dihydrotestosterone were measured by gas chromatography-mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with vitamin D using multinomial logistic regression. RESULTS: In univariate analyses, free T levels were lower (P=0.02) and E(2) and LH levels were higher (P<0.05) in men with vitamin D deficiency (25(OH)D <50 nmol/l). 25(OH)D was positively associated with total and free T and negatively with E(2) and LH in age- and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, vitamin D deficiency was significantly associated with compensated (relative risk ratio (RRR)=1.52, P=0.03) and secondary hypogonadism (RRR=1.16, P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001). CONCLUSIONS: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation. PMID- 22048969 TI - Successful treatment of congenital hyperinsulinism with long-acting release octreotide. AB - CONTEXT: Congenital hyperinsulinism (HI) is a common cause of hypoglycemia in infancy. The medical treatment of diazoxide-unresponsive HI is based on a somatostatin analogue. OBJECTIVE: This study aims at replacing three daily s.c. octreotide (Sandostatin, Novartis) injections by a single and monthly i.m. injection of long-acting release (LAR) octreotide (Sandostatin LP, Novartis) in HI patients. SUBJECTS AND METHOD: LAR octreotide was injected every 4 weeks during 6 months and s.c. octreotide injections were stopped after the third injection of LAR octreotide. After this 6-month study, LAR octreotide was continued, with an average follow-up of 17 months. Ten HI pediatric patients unresponsive to diazoxide and currently treated with s.c. octreotide were included in the trial. Glycemias and other parameters (HbA1c, IGF1, height, weight, quality of life (QoL), and satisfaction) were monitored at each monthly visit. RESULTS: For all ten patients, glycemias were maintained in the usual range, HbAlc (mean 5.5%; 95% CI: 4.6-6.2) and IGF1 (mean 89.7 ng/ml; 95% CI: 26 153) were unchanged. Patients gained height significantly (mean 2.7 cm; 95% CI: 1.9-3.4) and no side effect was noted during the study and the later follow-up. Plasma octreotide levels were stable under LAR octreotide. Parents' questionnaires of general satisfaction were highly positive whereas children's QoL evaluation remained unchanged. CONCLUSION: In these diazoxide-unresponsive HI patients, LAR octreotide was efficient, well tolerated and contributed to a clear simplification of the medical care. PMID- 22048970 TI - Reproductive function in men affected by X-linked adrenoleukodystrophy/adrenomyeloneuropathy. AB - BACKGROUND: X-linked adrenoleukodystrophy (X-ALD) is the most frequent, severely neurodegenerative, clinically heterogeneous peroxisomal disorder, the signs of which are a consequence of myelin, adrenal cortex, and testes impairment. OBJECTIVE: We studied testosterone, LH, and FSH levels in X ALD/adrenomyeloneuropathy (AMN) patients. We evaluate the ability to procreate of these patients by analysis of pedigree and family screening by detection of very long-chain fatty acid (VLCFA) levels. SUBJECT AND METHODS: Seventeen patients with X-ALD/AMN (16 with AMN and one asymptomatic) aged 24-48 (mean+/-S.D., 34.7+/ 5.9) years, were identified based on the clinical picture, magnetic resonance imaging, and the presence of increased serum VLCFA levels. Nine X-ALD/AMN patients' daughters, mean ages +/-S.D.=7.7+/-3.8 years, were identified as heterozygote by elevated VLCFA levels. Serum VLCFA levels were determined as ester derivatives by a gas chromatography method. Serum testosterone, LH, and FSH levels in X-ALD/AMN patients were detected by IRMAs. RESULTS: Serum testosterone levels were at the lowest levels of normal range but serum LH and FSH concentrations were increased in 57.1 and in 42.9% of X-ALD/AMN patients respectively. Among the 11 investigated of X-ALD/AMN married adult men, nine had produced offspring, a total of 13 children. All patients' daughters showed elevated serum VLCFA at heterozygote levels. CONCLUSION: In this study, we report that in a group of X-ALD/AMN married adult men, we did not find a significant decrease in fertility compared with the Polish population (18.2 vs 15%). PMID- 22048971 TI - High-dose mitotane strategy in adrenocortical carcinoma: prospective analysis of plasma mitotane measurement during the first 3 months of follow-up. AB - BACKGROUND: The benefit-to-risk ratio of a high-dose strategy at the initiation of mitotane treatment of adrenocortical carcinoma (ACC) remains unknown. METHODS: To evaluate the performance of a high-dose strategy, defined as the highest tolerated dose administered within 2 weeks and maintenance therapy over 4 weeks, we conducted a single-center, prospective study with two main objectives: to evaluate the percentage of patients who achieve a plasma mitotane level above 14 mg/l and to evaluate the tolerance of mitotane within the first 3 months of treatment. Plasma mitotane levels were measured monthly using HPLC. RESULTS: Twenty-two patients with ACC were prospectively enrolled. The high-dose mitotane strategy (4 g/day or more in all patients, with a median of 6 g/day within 2 weeks) enabled to reach the therapeutic threshold of >14 mg/l at 1, 2, or 3 months in 6/22 patients (27%), 7/22 patients (32%), and 7/22 patients (32%) respectively. In total, a therapeutic plasma mitotane level was reached in 14 out of 22 patients (63.6%) during the first 3 months in ten patients, and after 3 months in four patients. Grade 3-4 neurological or hematological toxicities were observed in three patients (13.6%). CONCLUSION: Employing a high-dose strategy at the time of mitotane initiation enabled therapeutic plasma levels of mitotane to be reached within 1 month in 27% of the total group of patients. If this strategy is adopted, we suggest that mitotane dose is readjusted according to plasma mitotane levels at 1 or/and 2 months and patient tolerance. PMID- 22048972 TI - Nuclear receptor NR5A2 and bone: gene expression and association with bone mineral density. AB - OBJECTIVE: There is growing evidence for a link between energy and bone metabolism. The nuclear receptor subfamily 5 member A2 (NR5A2) is involved in lipid metabolism and modulates the expression of estrogen-related genes in some tissues. The objective of this study was to explore the influence of NR5A2 on bone cells and to determine whether its allelic variations are associated with bone mineral density (BMD). DESIGN: Analyses of gene expression by quantitative PCR and inhibition of NR5A2 expression by siRNAs were used to explore the effects of NR5A2 in osteoblasts. Femoral neck BMD and 30 single nucleotide polymorphisms (SNPs) were first analyzed in 935 postmenopausal women and the association of NR5A2 genetic variants with BMD was explored in other 1284 women in replication cohorts. RESULTS: NR5A2 was highly expressed in bone. The inhibition of NR5A2 confirmed that it modulates the expression of osteocalcin, osteoprotegerin, and podoplanin in osteoblasts. Two SNPs were associated with BMD in the Spanish discovery cohort (rs6663479, P=0.0014, and rs2816948, P=0.0012). A similar trend was observed in another Spanish cohort, with statistically significant differences across genotypes in the combined analysis (P=0.03). However, the association in a cohort from the United States was rather weak. Electrophoretic mobility assays and studies with luciferase reporter vectors confirmed the existence of differences in the binding of nuclear proteins and the transcriptional activity of rs2816948 alleles. CONCLUSIONS: NR5A2 modulates gene expression in osteoblasts and some allelic variants are associated with bone mass in Spanish postmenopausal women. PMID- 22048973 TI - Analysis of plasma ghrelin in patients with medium-chain acyl-CoA dehydrogenase deficiency and glutaric aciduria type II. AB - OBJECTIVE: Ghrelin requires a fatty acid modification for binding to the GH secretagogue receptor. Acylation of the Ser3 residue of ghrelin is essential for its biological activities. We hypothesized that acyl-CoA is the fatty acid substrate for ghrelin acylation. Because serum octanoyl-CoA levels are altered by fatty acid oxidation disorders, we examined circulating ghrelin levels in affected patients. MATERIALS AND METHODS: Blood levels of acyl (A) and des-acyl (D) forms of ghrelin and acylcarnitine of patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and glutaric aciduria type II (GA2) were measured. RESULTS: Plasma acyl ghrelin levels and A/D ratios increased in patients with MCAD deficiency or GA2 when compared with normal subjects. Reverse phase HPLC confirmed that n-octanoylated ghrelin levels were elevated in these patients. CONCLUSION: Changing serum medium-chain acylcarnitine levels may affect circulating acyl ghrelin levels, suggesting that acyl-CoA is the substrate for ghrelin acylation. PMID- 22048974 TI - Continuous glucose monitoring: coming of age? AB - In a recent issue of the Journal of Clinical Endocrinology and Metabolism, an Endocrine Society Clinical Practice Guideline on Continuous Glucose Monitoring (CGM) was published, co-sponsored by the European Society of Endocrinology. Such a guideline is a necessary step in the maturation of any new technology. This commentary tries to delineate where we stand some 10 years after the first retrospective CGM device entered the market from a European perspective. PMID- 22048975 TI - Evidence that polymorphisms in detoxification genes modulate the susceptibility for sporadic medullary thyroid carcinoma. AB - AIM: Polymorphic low-penetrance genes have been consistently associated with the susceptibility to a series of human tumors, including differentiated thyroid cancer. METHODS: To determine their role in medullary thyroid cancer (MTC), we used TaqMan SNP method to genotype 47 sporadic MTC (s-MTC) and a control group of 578 healthy individuals for CYP1A2*F, CYP1A1m1, GSTP1, NAT2 and 72TP53. A logistic regression analysis showed that NAT2C/C (OR=3.87; 95% CI=2.11-7.10; P=2.2*10(-5)) and TP53C/C genotypes (OR=3.87; 95% CI=1.78-6.10; P=2.8*10(-4)) inheritance increased the risk of s-MTC. A stepwise regression analysis indicated that TP53C/C genotype contributes with 8.07% of the s-MTC risk. RESULTS: We were unable to identify any relationship between NAT2 and TP53 polymorphisms suggesting they are independent factors of risk to s-MTC. In addition, there was no association between the investigated genes and clinical or pathological features of aggressiveness of the tumors or the outcome of MTC patients. CONCLUSION: In conclusion, we demonstrated that detoxification genes and apoptotic and cell cycle control genes are involved in the susceptibility of s MTC and may modulate the susceptibility to the disease. PMID- 22048976 TI - Endovascular treatment of isolated internal iliac artery aneurysms. AB - The aim of the paper is to evaluate the outcome of endovascular treatments for isolated internal iliac artery aneurysms. A systematic review of the literature using public domain databases was undertaken. All studies reporting on endovascular treatment of isolated hypogastric artery aneurysms were considered. Experience from our institution was involved in the data analysis. The primary outcome measures were technical success, perioperative, and overall mortality and morbidity. Data were extracted from 30 articles fulfilling the selection criteria, and the study cohort consisted of 55 patients having undergone treatment of 59 internal iliac artery aneurysms. Ten patients (18%) were treated on an urgent or emergency basis for a ruptured aneurysm. Technical success was achieved in 71% of the cases. The most common reason for technical failure was incomplete exclusion of the aneurysm sac. Thirty-day mortality occurred in one patient (2%). The 30-day morbidity rate was 20%, and was mostly associated with insufficiency of the pelvic circulation. One aneurysm-related death occurred during a mean follow-up period of 13 months (range 0.5-56 months). Open surgical intervention for aneurysm-related complications was required in five patients. In conclusion, endovascular treatment of isolated internal iliac artery aneurysms is an effective alternative option, with satisfactory early and mid-term results. PMID- 22048977 TI - Hypothenar hammer syndrome in a 22-year-old male patient: a case report and review of literature. AB - Hypothenar hammer syndrome is a rare condition with a peculiar presentation that aids in making a clinical diagnosis. We present a 22-year-old male patient who presented with critical hand ischemia secondary to a distal ulnar aneurysm with distal embolization. The patient was treated with an aneurysmectomy with cephalic vein interposition graft, which resulted in complete reversal of his hand ischemia. This case report outlines the clinical presentation of this rare condition, along with a recent review of the literature. PMID- 22048978 TI - Autism, imprinting and epigenetic disorders: a metabolic syndrome linked to anomalies in homocysteine recycling starting in early life?? PMID- 22048979 TI - Current and emerging treatment options for castration-resistant prostate cancer: a focus on immunotherapy. AB - BACKGROUND: Castration-resistant prostate cancer is a disease with limited treatment options. However, the ongoing elucidation of the mechanisms underlying this disease continues to support the development of not only novel agents, but also innovative approaches. Among these therapies, immunotherapy has emerged as a promising strategy. DESIGN: This review article summarizes the most recent data from investigations of immunotherapies in castration-resistant prostate cancer (literature and congress searches current as of August 2011). RESULTS: Immunotherapeutic strategies such as passive immunization, vaccines, and particularly checkpoint blockade have demonstrated some efficacy as single agents. Elucidation of effective combinations of agents and drug regimens is ongoing but will require continued careful investigation, including the standardization of surrogate endpoints in clinical trials. CONCLUSIONS: It is hypothesized that the combination of immunotherapeutic agents with traditional and novel chemotherapeutics will potentiate the efficacy of the chemotherapeutics while maintaining manageable toxicity. PMID- 22048980 TI - TLR-mediated B cell defects and IFN-alpha in common variable immunodeficiency. AB - Common variable immune deficiency (CVID) B cells have impaired responses to TLR7 and TLR9 agonists including poor cell proliferation, loss of cytokine production, and failure to produce IgG or IgA. We show that TLR7- or 9-activated B cells from CVID subjects with >0.5% peripheral isotype-switched CD27(+) B cells (group 2) have increased mature Cgamma1 and Cgamma2 heavy-chain mRNA transcripts compared to subjects who have <0.5% isotype-switched cells (group 1). While TLR-stimulated CVID plasmacytoid dendritic cells for all subjects had impaired IFN-alpha production, TLR7 or TLR9 stimulation in the presence IFN-alpha normalized isotype switched CD27(+) B cells, enhanced activation-induced cytidine deaminase mRNA, and significantly improved IgG production only for group 2 subjects. IFN-alpha also upregulated TLR7 and TLR9 mRNA expression comparable to normal levels in B cells of group 2 subjects, indicating that the loss of IFN-alpha could be a significant component of the B-cell defect for these subjects. PMID- 22048981 TI - Investigation of the atrial electromechanical delay duration in Behcet patients by tissue Doppler echocardiography. AB - AIMS: To investigate the atrial electromechanical delay (EMD) duration that is a non-invasive predictor of atrial fibrillation (AF) in patients with Behcet's disease (BD). METHODS AND RESULTS: Thirty-eight Behcet's patients (24 females, 14 males; mean age: 43.6 +/- 10.3 years) who were being followed in the dermatology or internal medicine department and 29 demographically matched controls (13 females, 16 males; mean: age 42.6 +/- 11.1 years) were included in the study. The inclusion criteria were recurrent oral ulcerations and two of the following features: recurrent genital ulceration, eye lesions, skin lesions or positive pathergy skin test for Behcet's group. Using tissue Doppler imaging, atrial electromechanical coupling [time interval from the onset of P wave on surface electrocardiogram to the beginning of A wave interval with tissue Doppler echocardiography (PA)] were measured from the lateral mitral annulus (PA lateral), septal mitral annulus (PA septum), and right ventricular tricuspid annulus (PA tricuspid). The mean disease duration was 10.5 +/- 7.7 years. The inter-atrial and intra-atrial EMD were significantly higher in the Behcet group than those in the controls (19.8 +/- 8.2 vs. 13.1 +/- 4.4 ms, P = 0.001; 11.5 +/- 7.4 vs. 6.9 +/- 3.7 ms, P = 0.02; respectively). The left atrial EMD was similar in both of the groups. However, the P(max) and PWD values were significantly higher in the BD group compared with those in the controls (120.5 +/- 10.1 vs. 112.1 +/- 5.9 ms, P < 0.0001; 44.9 +/- 10.7 vs. 28.4 +/- 5.9 ms, P < 0.0001; respectively). CONCLUSION: Atrial electromechanical conduction times were increased in the BD patients compared with those in the controls. The tendency of BD patients to go into AF can be easily and non-invasively detected using tissue Doppler echocardiography. These findings may be indicators for subclinical cardiac involvement. PMID- 22048982 TI - A complicated transseptal puncture during Mitraclip procedure: saved by 3D-TEE. AB - We report a case where real-time three-dimensional transoesophageal echocardiography (3D-TEE) was able to detect a complicated transseptal puncture during a Mitraclip procedure which was not seen on the two-dimensional TEE (2D TEE) images. This case demonstrates the incremental value of 3D-TEE during transseptal puncture. PMID- 22048983 TI - Fluorescence and electrochemical sensing of pesticides methomyl, aldicarb and prometryne by the luminescent europium-3-carboxycoumarin probe. AB - This work describes the application of time resolved fluorescence in microtiterplates and electrochemical methods on glassy carbon electrode for investigating the interactions of europium-3-carboxycoumarin with pesticides aldicarb, methomyl and prometryne. Stern-volmer studies at different temperatures indicate that static quenching dominates for methomyl, aldicarb and prometryne. By using Lineweaver-Burk equation binding constants were determined at 303 K, 308 K and 313 K. A thermodynamic analysis showed that the reaction is spontaneous with DeltaG being negative. The enthalpy DeltaH and the entropy DeltaS of reactions were all determined. A time-resolved (gated) luminescence-based method for determination of pesticides in microtiterplate format using the long-lived europium-3-carboxycoumarin has been developed. The limit of detection is 4.80, 5.06 and 8.01 MUmol L(-1) for methomyl, prometryne and aldicarb, respectively. This is the lowest limit of detection achieved so far for luminescent lanthanide based probes for pesticides. The interaction of the probe with the pesticides has been investigated using cyclic voltammetry (CV), differential pulse polarography (DPP), square wave voltammetry (SWV) and linear sweep voltammetry (LSV) on a glassy carbon electrode in I = 0.1 mol L(-1) p-toluenesulfonate at 25 degrees C. The diffusion coefficients of the reduced species are calculated. The main properties of the electrode reaction occurring in a finite diffusion space are the quasireversible maximum and the splitting of the net SWV peak for Eu(III) ions in the ternary complex formed . It was observed that the increase of the cathodic peak currents using LSV is linear with the increase of pesticides concentration in the range 5 * 10(-7) to 1 * 10(-5) mol L(-1). The detection limit (DL) were about 1.01, 2.23 and 1.89 MUmol L(-1) for aldicarb, methomyl and prometryne, respectively. In order to assess the analytical applicability of the method, the influence of various potentially interfering species was examined. Influence of interfering species on the recovery of 10 MUmol L(-1) pesticides has been investigated. PMID- 22048984 TI - Luminescence properties of dual valence Eu doped nano-crystalline BaF2 embedded glass-ceramics and observation of Eu2+ -> Eu3+ energy transfer. AB - Europium doped glass-ceramics containing BaF(2) nano-crystals have been prepared by using the controlled crystallization of melt-quenched glasses. X-ray diffraction and transmission electron microscopy have confirmed the presence of cubic BaF(2) nano-crystalline phase in glass matrix in the ceramized samples. Incorporation of rare earth ions into the formed crystalline phase having low phonon energy of 346 cm(-1) has been demonstrated from the emission spectra of Eu(3+) ions showing the transitions from upper excitation states (5)D(J) (J = 1, 2, and 3) to ground states for the glass-ceramics samples. The presence of divalent europium ions in glass and glass-ceramics samples is confirmed from the dominant blue emission corresponding to its 5d-4f transition under an excitation of 300 nm. Increase in the reduction of trivalent europium (Eu(3+)) ions to divalent (Eu(2+)) with the extent of ceramization is explained by charge compensation model based on substitution defect mechanisms. Further, the phenomenon of energy transfer from Eu(2+) to Eu(3+) ion by radiative trapping or re-absorption is evidenced which increases with the degree of ceramization. For the first time, the reduction of Eu(3+) to Eu(2+) under normal air atmospheric condition has been observed in a BaF(2) containing oxyfluoride glass-ceramics system. PMID- 22048985 TI - Diabetes self-efficacy strongly influences actual control of diabetes in patients attending a tertiary hospital in India. AB - A cross-sectional survey of 507 in- and out-patients, with diagnosed Type 2 diabetes mellitus (T2DM) was undertaken to study the relationships between personal, disease and treatment-related factors and diabetes control in a tertiary care hospital. On multivariate logistic regression analysis, self efficacy (odds ratio (OR) =2.94; 95% confidence interval (CI) =1.92-4.54); P<0.001) was the single most important determinant of current diabetes control (HbA1c <=7%), along with absence of hyperglycemic symptoms in the past year (OR=1.83; 95% CI=1.15-2.93, P<0.01), current treatment with oral medication (OR=1.77; 95% CI=1.17-2.66; P<0.007), and adherence to dietary restrictions (OR=2.7; 95% CI=1.28-5.88; P<0.009). Self-efficacy was itself influenced by educational status, employment, availability of family support, and positive mental attitudes. Our findings suggest that health care delivery inputs, patients' personal characteristics including education and attitude, and family support for care are complexly processed to determine patients' ability to manage their disease, which ultimately influences disease outcomes. PMID- 22048986 TI - Factors influencing colorectal cancer screening in low-income African Americans in Tennessee. AB - This study examined demographic and lifestyle factors that influenced decisions and obstacles to being screened for colorectal cancer in low-income African Americans in three urban Tennessee cities. As part of the Meharry Community Networks Program (CNP) needs assessment, a 123-item community survey was administered to assess demographic characteristics, health care access and utilization, and screening practices for various cancers in low-income African Americans. For this study, only African Americans 50 years and older (n=460) were selected from the Meharry CNP community survey database. There were several predictors of colorectal cancer screening such as being married and having health insurance (P< .05). Additionally, there were associations between obstacles to screening and geographic region such as transportation and health insurance (P< .05). Educational interventions aimed at improving colorectal cancer knowledge and screening rates should incorporate information about obstacles and predictors to screening. PMID- 22048987 TI - Achy breaky makey wakey heart? A randomised crossover trial of musical prompts. AB - OBJECTIVE: Compared with no music (NM), does listening to 'Achy breaky heart' (ABH) or 'Disco science' (DS) increase the proportion of prehospital professionals delivering chest compressions at 2010 guideline-compliant rates of 100-120 bpm and 50-60 mm depths? METHODS: A randomised crossover trial recruiting at an Australian ambulance conference. Volunteers performed three 1-min sequences of continuous chest compressions on a manikin accompanied by NM, repeated choruses of ABH and DS, prerandomised for order. RESULTS: 37 of 74 participants were men; median age 37 years; 61% were paramedics, 20% students and 19% other health professionals. 54% had taken cardiopulmonary resuscitation training within 1 year. Differences in compression rate (mode, IQR) were significant for NM (105, 99-116) versus ABH (120, 107-120) and DS (104, 103-107) versus ABH (p<0.001) but not NM versus DS (p=0.478). Differences in proportions of participants compressing at 100-120 bpm were significant for DS (61/74, 82%) versus NM (48/74, 65%, p=0.007) and DS versus ABH (47/74, 64%, p=0.007) but not NM versus ABH (p=1). Differences in compression depth were significant for NM (48 mm, 46-59 mm) versus DS (54 mm, 44-58 mm, p=0.042) but not NM versus ABH (54 mm, 43-59 mm, p=0.065) and DS versus ABH (p=0.879). Differences in proportions of subjects compressing at 50-60 mm were not significant (NM 31/74 (42%); ABH 32/74 (43%); DS 29/74 (39%); all p>0.5). CONCLUSIONS: Listening to DS significantly increased the proportion of prehospital professionals compressing at 2010 guideline-compliant rates. Regardless of intervention more than half gave compressions that were too shallow. Alternative audible feedback mechanisms may be more effective. PMID- 22048988 TI - Hormone-dependent placental manipulation of breast cancer cell migration. AB - BACKGROUND: Breast cancer during pregnancy is often more advanced than in non pregnant women. Nevertheless, no case of metastasis inside the placenta has been reported. Previously, we showed that placental-explants eliminated breast cancer cells from their surroundings, due to cell-death and elevated migration. Our objective was to find the underlying mechanisms of these phenomena. METHODS AND RESULTS: Our model contained Michigan Cancer Foundation 7 (MCF7) or T47D cells co cultured with and without human placental explants. Microarray analysis, validated by quantitative PCR, of MCF7 following their placental co-culture suggested activation of estrogen (E(2)) signaling. As extensive cross-talk exists between E(2) and progesterone, their involvement in mediating placental effects on breast cancer cells was tested. Indeed, addition of E(2) and progesterone receptor (ER and PR) inhibitors to the co-culture system reduced cancer cell motility, yet did not alter cell-cycle or death. E(2) and progesterone concentrations in placental media were found to be similar to those of early pregnancy blood levels. Interestingly, placental-breast cancer co-culture media contained lower progesterone (P < 0.05) and higher E(2) (200%, P < 0.05) levels than placentae cultured separately. Placental supernatant and E(2) and progesterone at placental levels were sufficient to increase MCF7 and T47D migration and invasion (P < 0.05), yet did not alter MCF7 cell-cycle or death. Furthermore, placental supernatant elevated p38 and Jun N-terminal kinase (JNK) phosphorylation in both cell lines (P < 0.05). Inhibitors of JNK, ER and PR reversed MCF7 and T47D motility induced by the placenta, suggesting their involvement. CONCLUSIONS: We suggest that E(2) and progesterone contribute to cell migration away from placental areas. We hypothesize that they may increase metastatic spread to other organs in pregnancy. PMID- 22048989 TI - Neonatal follow-up of 995 consecutively born children after embryo biopsy for PGD. AB - BACKGROUND: Outcome data on children born after assisted reproduction treatments are important for both patients and health-care providers. The objective of this study was to determine whether embryo biopsy as performed in PGD has an impact on the health of infants up to 2 months of age. METHODS: A prospective comparative follow-up study of children born after PGD and children born after ICSI by collecting written reports and performing a physical examination at 2 months was performed. Auxological data at birth and physical findings up to 2 months of age were compared for 995 children consecutively live born after embryo biopsy (1994 2009) and for a control group of 1507 children born after ICSI with embryo transfer on Day 5. RESULTS: No differences regarding mean term, prematurity (term <32 w and <37 w), mean birthweight, very low birthweight (<1500 g), perinatal death, major malformations and neonatal hospitalizations in singletons and multiples born following PGD versus ICSI were observed. Compared with ICSI, fewer multiples born following PGD presented a low birthweight (<2500 g) (P = 0.005). CONCLUSIONS: Embryo biopsy for PGD does not introduce extra risk to the overall medical condition of newborn children. Multiples born following embryo biopsy appear to be at lower risk for low birthweight compared with multiples born following ICSI. PMID- 22048990 TI - Parenthood motives, well-being and disclosure among men from couples ready to start treatment with intrauterine insemination using their own sperm or donor sperm. AB - BACKGROUND: As pregnancy and childbirth have long been considered women's issues and male infertility has long been surrounded by taboo, limited research has focused on the experience of infertile men. The purpose of this study was to compare male motives for parenthood, male well-being and disclosure patterns concerning the method of conception among men from couples starting treatment with IUI using their own sperm (autologous sperm recipient, ASR) or donor sperm (donor sperm recipient, DSR). METHODS: This prospective study included 46 DSR- and 151 ASR-couples. Self-report questionnaires assessing parenthood motives, well-being and disclosure patterns concerning the method of conception were administered to both men and women prior to treatment. Unpaired T-tests and Fisher's exact tests were used to test for significant differences. RESULTS: When compared with ASR-men, DSR-men expect more positive effects from parenthood on relationships and feelings of fulfilment, and report less negative effects of infertility on sexuality, but a lower self-image and more guilt. DSR-men plan to disclose the method of conception less frequently and have so far disclosed to a lesser degree than ASR-men. CONCLUSIONS: DSR-men feel differently about parenthood and infertility compared with ASR-men, and their higher expectations combined with lower self-esteem need (more) attention during counselling. PMID- 22048991 TI - Perspectives of mild cycle IVF: a qualitative study. AB - BACKGROUND: The introduction of mild cycle IVF adds to the repertoire of fertility treatments. However, its place is still novel and is contested within the literature. Women's experiences of mild cycle IVF have received minimal attention. The aim of the study was to explore women's perspectives regarding mild cycle IVF. METHODS: In this qualitative thematic analysis study, 17 women, and 2 partners were interviewed regarding their perceptions of 'mild' cycle IVF. Data were thematically analysed to identify the key aspects of participants' perceptions. RESULTS: Participants reported that 'mild' cycle IVF offered a number of positive aspects, including the reduction in the intrusion of IVF procedures in women's lives, the short timeframe spent in awaiting the results and the way mild cycle worked with women's natural hormonal cycles. CONCLUSIONS: 'Mild' cycle IVF was perceived positively by the participants particularly in terms of timeframes and the impact on their physical and emotional wellbeing. PMID- 22048992 TI - Donor age is a major determinant of success of oocyte donation/recipient programme. AB - BACKGROUND: In recent years, particularly in developed countries, women have tended to delay childbirth until over 40 years of age. Our study aims to identify whether the donor's age or recipient's age influences the pregnancy and live birth rate following oocyte recipient cycles. METHODS: A population study included 3889 fresh oocyte recipient cycles. Pregnancy and live delivery rates were compared in recipient age groups (<35, 35-39, 40-44 and >=45 years) and donor age groups (<30, 30-34, 35-39 and >=40 years). RESULTS: The highest live birth rate was of cycles in donors aged 30-34 years (25.0%), it decreased (P< 0.05) to 24.1% in donors aged <30 years, 20.7% in donors aged 35-39 years and 11.5% in donors aged >=40 years. The multivariate analysis showed no significant differences in the success by recipient's age. Compared with cycles in donors aged 30-34 years, cycles in donors aged 35-39 years had 14 and 18% less chance to achieve a pregnancy [adjusted rate ratio (ARR) 0.86, 95% confidence interval (CI) 0.75-0.98] and a live delivery (ARR 0.82, 95% CI 0.71-0.96), while cycles in donors aged 40 years or older had 42 and 54% less chance to achieve a pregnancy (ARR 0.58, 95% CI 0.41-0.84) and a live delivery (ARR 0.46, 95% CI 0.29-0.73). CONCLUSIONS: Older recipients with younger donors did not have a poorer pregnancy outcome compared with younger recipients with younger donors. Choosing a donor aged <35 years would increase the chance of pregnancy and live delivery for older recipients. PMID- 22048993 TI - A standardized education protocol significantly reduces traumatic injuries and syncope recurrence: an observational study in 316 patients with vasovagal syncope. AB - AIMS: The aim of this study was to assess the role of a non-pharmacological approach on the frequency of traumatic injuries and syncope recurrence in patients with vasovagal syncope and normal hearts. We report the experience in our syncope centre with a standardized education and teaching protocol for patients with vasovagal syncope. The treatment of vasovagal syncope is often complex and discouraging. Besides medical options, behaviour modification is a main component of therapy but has no statistical evidence to support its use. METHODS AND RESULTS: Between January 1999 and September 2006, we prospectively enrolled all patients with vasovagal syncope. The patients were counselled about the benign nature of their disease. Specific recommendations were made according to a standardized education protocol established at our syncope centre. A pre /post-study was conducted to investigate the effectiveness of our approach on syncope recurrence and frequency of injury as the study endpoints. Complete follow-up data were available from 85% of the study population (316 of 371) after a mean time of 710 +/- 286 days (mean age 50 years; standard deviation +/- 18 years, 160 female). Eighty-seven patients (27.5%) had a syncope recurrence with 22 suffering an injury during syncope. During the follow-up period, the syncope burden per month was significantly reduced from 0.35 +/- 0.03 at initial presentation to 0.08 +/- 0.02 (P< 0.001). The frequency of traumatic syncope was significantly lower at the time of recurrence compared with the initial presentation (25 vs. 42%; McNemar's test P= 0.02). CONCLUSION: A standardized education protocol significantly reduces traumatic injuries and syncope recurrence in patients with vasovagal syncope. PMID- 22048994 TI - Clinical and electrophysiological characteristics in patients with sustained monomorphic reentrant ventricular tachycardia associated with dilated-phase hypertrophic cardiomyopathy. AB - AIMS: Little is known about sustained monomorphic ventricular tachycardia (SMVT) associated with dilated-phase hypertrophic cardiomyopathy (DHCM). The purpose of this study was to clarify the clinical characteristics and effectiveness of catheter ablation for SMVTs in DHCM patients. METHODS AND RESULTS: Five patients with DHCM (mean age; 67.0 years old, five males) who underwent catheter ablation for drug-refractory SMVTs were included the study. Four of five patients suffered from electrical storm. When the endocardial ablation failed, epicardial and/or intracoronary ethanol ablation, or surgical cryoablation was performed. We reviewed all ablation procedures and electrocardiogram (ECG) of targeted SMVTs. A total of 13 SMVTs were targeted for ablation. Mechanism of all ventricular tachycardias (VTs) was diagnosed as reentry. Endocardial ablation successfully eliminated all VTs in two patients. The remaining three patients needed epicardial ablation, intracoronary ethanol ablation, and surgical cryoablation. All but one VT arose from the basal septum, basal anterior to anterolateral left ventricle (LV). Although the ECGs demonstrated similar features of idiopathic outflow or mitral annulus VTs reflecting the origins, there were characteristic multiple QRS deflections. Following the ablation, four (80%) of the five patients are free from VT recurrence during 18 months of the follow-up period. CONCLUSIONS: In DHCM patients, VT circuits predominantly distributed in the basal septum and the basal anterior to anterolateral LV. In addition to the endocardial ablation, alternative approaches were required in some patients. PMID- 22048995 TI - The new emphasis on implementing evidence-based interventions: the end of research or a new beginning for partnerships? PMID- 22049001 TI - Editorial. PMID- 22049000 TI - Young men, sexual health and responsibility for contraception: a qualitative pilot study. AB - BACKGROUND AND METHODOLOGY: Despite increasing interest over the last decade or more in men's views of sexual health services and use of contraception, most published literature focuses on women. It is important that the views of boys and young men are better understood, particularly with regard to responsibility for use of contraception. This pilot study aimed to gain insights into young men's views of sexual health services and contraception; five non-fathers aged between 14 and 18 years took part in two focus groups. The groups were recorded, transcribed and analysed using the constant comparative method to build up categories of data. RESULTS: Engaging young men in research is very difficult, particularly young men who are not in education or employment. Young fathers proved impossible to recruit. The young men who took part in the study thought responsibility for contraception was shared, although this was partly dependent on relationship status, namely whether sex was with a regular partner or a one night stand. DISCUSSION AND CONCLUSIONS: These findings are based on a small sample and all participants were in full-time education. It is likely that attitudes may differ from those who are not in education, training or employment. In a future study, it would be important to ensure that young men from different class and educational backgrounds are included in the research, as the tentative conclusions from this pilot study suggest that educational status is a factor in beliefs about responsibility. PMID- 22049002 TI - A pragmatic basis for judging models and theories in health psychology: the axiomatic method. AB - Psychology and its subfield of health psychology suffer from a lack of standardized terminology and a unified theoretical framework for the prediction and explanation of health behaviour. Hence, it is difficult to establish whether a given theory is logically consistent and to compare different theories. Science involves both empirical and conceptual issues. It is asserted that psychology has overemphasized the former and underemphasized the latter. Empirical psychology needs an explicit, shared conceptual system in order to develop its theories. An example of an axiomatic method (Psycho-Logic; see e.g. J. Smedslund.Psychological Inquiry 1991a; 2: 325-338) is applied to show how the Health Belief Model,the Theory of Planned Behaviour and Social Cognitive Theory all conform to the a priori conditions of acting. One implication is that studies of the predictive power of theories stated as definitional truths only assess auxiliary hypotheses, i.e. the extent to which the measuring instruments are reliable and valid. On the other hand, the introduction of logic into health psychology can facilitate genuine empirical studies by helping to avoid so-called 'pseudoempirical' work (Smedslund, J. In Smith, Harre & Van Langenhove (Eds.) Rethinking psychology, 1995). Systems such as Psycho-Logic can also enhance conceptual integration by using logic to explicate and demonstrate intuitive relations. Implications for practitioners are discussed briefly. PMID- 22049003 TI - On judging models and theories: research and practice, psychology and public health. PMID- 22049004 TI - Alternative pragmatic bases for judging models. PMID- 22049005 TI - Logic, empiricism and ethics. PMID- 22049006 TI - Logic or Psychologism: Smedslund's Psycho-Logic and Health. PMID- 22049007 TI - Psycho-logic: a 'conceptual toolbox' and 'mind sharpener' for health psychologists: a response to commentaries. AB - This is a reply to K. Glanz, J. Maddock, J. O. Prochaska, D. Seedhouse, and H. Stam on the target article entitled: 'A pragmatic basis for judging models and theories in health psychology: the axiomatic method'. I defend the claim that one should only test hypotheses that are empirical and avoid testing hypotheses that are necessarily true because of conceptual relations and logic. I argue that the axiomatic system Psycho-Logic (PL) should be added to the other methods which form the health psychologist's methodological 'toolbox'. PMID- 22049008 TI - Transdisciplinary work with psychology from a population health perspective: an illustration. AB - One of the important implications of a population health perspective in public health is an increase in the need for transdisciplinary ways of working. The Community Health Research Unit (CHRU) is presented as an example of an environment where psychology and psychologists work with other disciplines to conduct applied research in population health. Research activities were examined to identify how the disciplines collaborate and to provide evidence of successful interdisciplinary and transdisciplinary approaches which incorporate health psychology. The strengths and challenges of multi-, inter-, and transdisciplinary approaches were examined through a poll of CHRU members. Further, members' views about the contributions of psychology to their work were gathered. Issues of working with different disciplines in a transdisciplinary approach are highlighted and future directions are suggested. PMID- 22049009 TI - Researcher Knows Best?: Toward a Closer Match between the Concept and Measurement of Coping. AB - Missing from recent critiques of coping measurement are data demonstrating whether concepts used by researchers are understood by study participants. We asked 101 rheumatoid arthritis patients to complete a structured coping checklist and provide descriptions of their coping for each item checked. Trained researchers coded these open-ended descriptions using the original checklist categories. In general, patients' descriptions of their coping matched researcherderived definitions; however, patients were less likely to interpret cognitive and affective coping strategies in the manner intended by researchers. Patients' descriptions often crossed multiple categories, suggesting complex patterns not captured by most data analytic techniques. Whether they assess coping through structured measures or not, researchers must find ways to examine the multiple meanings and combinations of strategies that constitute the coping process. Keywords. PMID- 22049010 TI - Assessment of Magical Beliefs about Food and Health. AB - The Magical Beliefs About Food and Health scale (MFH) was developed to assess individual differences in the tendency to adopt eating and health instructions that many magazines, health care books and food ideologies regard as valid but which obey universal laws of similarity and contagion. In a study of 216 individuals, the total MFH score showed good internal consistency and it was associated with various validity criteria as hypothesized (e.g. vegetarianism and other ideological commitments to food choice, female gender, increased neuroticism, experiential thinking, positive attitudes towards alternative medicine, low sensation seeking and endorsement of universalism values). Factor analysis yielded two factors: General Magical Beliefs and Animal Products as Food Contaminants. In addition, three other items (the Animal Products as Personality Contaminants scale) cross-loaded on the two factors. The factor structure and test-retest reliability were confirmed with separate samples. The results showed that the total MFH score is a reliable and valid measure of magical food and health beliefs, and that the subscales may prove useful when a multidimensional assessment of magical beliefs is needed. PMID- 22049011 TI - Racial segregation and cigarette smoking among blacks: findings at the individual level. AB - This study explored the role of racial segregation in cigarette smoking among US blacks. Five hundred and twenty black adults sampled door-to-door in 10 randomly selected, southern California census tracts completed a survey assessing their degree of racial segregation, experiences with racial discrimination, smoking, and income. Results revealed that the prevalence of smoking among highly segregated blacks (32.9 percent) was significantly higher than that of their less segregated cohorts (19.9 percent). Income, gender, and experiences with racial discrimination did not play a role in smoking but low education levels contributed. Early childhood segregation appeared to be the specific segregation variable associated with smoking among black adults. PMID- 22049012 TI - Problematic and positive support in relation to depression in people with rheumatoid arthritis. AB - This study focuses on the associations of both positive and problematic aspects of social support with depression in patients with rheumatoid arthritis. In a hierarchical multiple regression analysis we found that stressors such as functional limitations and pain are strongly related to depression. Positive and problematic support each explain an additional significant portion of the variance in depression. More positive support is associated with fewer feelings of depression and more problematic support is associated with more feelings of depression. An interaction effect between positive and problematic social support indicates that the negative aspects of problematic support may be partly diminished by positive support (buffering effect). Patients receiving more problematic support and less positive support experience the most feelings of depression. PMID- 22049013 TI - The effect of prescribed and preferred intensity exercise on psychological affect and the influence of baseline measures of affect. AB - This study compared the effects of 20 minutes of treadmill exercise at a prescribed intensity exercise (65% VO(2)max) and a preferred intensity exercise on psychological affect and exercise enjoyment in aerobically fit individuals. Affect was measured before exercise, at 5-minute intervals during exercise and 5 minutes post-exercise. Heart rate, ratings of perceived exertion (RPE) and enjoyment were also measured during each session. Results indicated that there was no difference in psychological affect or enjoyment between the two exercise sessions, although work rate was higher in the preferred condition. However, pre exercise values of affect played an influential role in the affective response to exercise. These results suggest that allowing fit individuals to select their own exercise intensity may be more beneficial physiologically and psychologically. PMID- 22049014 TI - Parents' Constructions of the 'Problem' during Assessment and Diagnosis of their Child for an Autistic Spectrum Disorder. AB - The majority of studies on the effects of a diagnosis of learning disability in the family have employed traditional 'loss' and 'stress reaction' paradigms. In contrast to this approach, the current analysis employed a form of discourse analysis to explore the ways in which parents represented the 'problem' during the process of assessment of their child for an autistic spectrum disorder. The analysis suggested that parents employed three main discourses in their talk about the 'problem', which were termed the discourse of normal development, the medical discourse and the discourse of disability. The ways in which these discourses were used in constructing the 'problem', their relationship to each other and the discursive work underlying the diagnosis are discussed. Although this study focused on the specific case of autism, it is suggested that the findings could inform thinking around the complex ways in which medical diagnosis is constructed by families and extend our understanding of this important aspect of health care practice. PMID- 22049015 TI - Handbook of stress, medicine and health. PMID- 22049016 TI - Handbook of pain syndromes. PMID- 22049017 TI - Women, stress, and heart disease. PMID- 22049018 TI - Representations of health, illness and handicap. PMID- 22049019 TI - Endoscopic management of sinonasal hemangiopericytoma. AB - OBJECTIVE: Sinonasal hemangiopericytomas (SNHPCs) are rare perivascular tumors with low-grade malignant potential. Traditionally, these tumors have been treated with open approaches such as lateral rhinotomy, Caldwell-Luc, or transfacial approaches. Increased experience with endoscopic management of benign and malignant sinonasal tumors has led to a shift in management of SNHPC. The authors present their experience in the largest series of patients with SNHPC managed endoscopically. STUDY DESIGN AND SETTING: Case series at a tertiary care medical center. SUBJECTS AND METHOD: A retrospective chart review of all patients undergoing endoscopic management of SNHPC at the University of Miami between 1999 and 2008 was conducted. All endoscopic resections were performed with curative intent. RESULTS: Twelve patients with the diagnosis of SNHPC were treated endoscopically. Mean age was 62.5 years (range, 51-83 years). There were 6 men and 6 women. The mean follow-up was 41 months (range, 15-91 months). Seven (58.3%) presented with nasal obstruction, whereas 4 (41.6%) had epistaxis as their initial presenting symptom. Preoperative angiography or embolization was not performed in any case. Mean estimated blood loss was 630 mL (range, 100-1500 mL). Six patients underwent endonasal endoscopic anterior skull base resection; 4 had complete endoscopic resection all with negative margins. None underwent postoperative adjuvant treatment. No recurrence or metastatic disease was observed in this patient population. CONCLUSION: Endoscopic management of SNHPC is a feasible approach and did not compromise outcomes in this experience. In this series, familiarity with advance endoscopic sinus surgery was necessary to manage these patients. Postoperative adjuvant therapy was not necessary in this cohort. PMID- 22049020 TI - Effects of anatomy and particle size on nasal sprays and nebulizers. AB - OBJECTIVE: To study the effects of nasal deformity on aerosol penetration past the nasal valve (NV) for varying particle sizes using sprays or nebulizers. STUDY DESIGN: Computed mathematical nasal airway model. SETTING: Department computer lab. SUBJECTS AND METHODS: Particle deposition was analyzed using a computational fluid dynamics model of the human nose with leftward septal deviation and compensatory right inferior turbinate hypertrophy. Sprays were simulated for 10 um, 20 um, 50 um, or particle sizes following a Rosin Rammler particle size distribution (10-110 um), at speeds of 1, 3, or 10 meters per second. Nebulization was simulated for 1, 3.2, 6.42, or 10 um particles. Steady state inspiratory airflow was simulated at 15.7 liters per minute. RESULTS: Sprays predicted higher NV penetration on the right side for particle sizes >10 um, with comparable penetration on both sides at 10 um. Nearly 100% deposited in the nasal passages for all spray characteristics. Nebulizer predictions showed nearly 100% of particles <6.42 um and more than 50% of 6.42 um bypassing both sides of the nose without depositing. Of the nebulized particles that deposited, penetration was higher on the right at 10 um, with comparable penetration on both sides at 6.42 um. Spray penetration was highest at 10 um, with more than 96% penetrating on both sides at 1 and 3 meters per second. Nebulization penetration was also highest at 10 um (40% on the left, >90% on the right). CONCLUSION: In the presence of a septal deviation, sprays or nebulizers containing 10-um particles may have good penetration beyond the NV. Nebulized particles <10 um are likely to be respirable. Additionally, spray speeds above 3 meters per second may limit penetration. PMID- 22049021 TI - A rat model for intracranial facial nerve crush injuries. AB - OBJECTIVE: (1) Explain the need for an animal model to study intracranial injuries to the facial nerve. (2) Describe various techniques attempted to identify and crush the intracranial segment of the facial nerve in a rat model. (3) Describe in detail a successful rat model of intracranial facial nerve crush injury. STUDY DESIGN: Randomized controlled animal study. SETTING: Animal laboratory. SUBJECTS AND METHODS: Multiple attempts at surgical approaches to the cerebellopontine angle were attempted on cadaveric rats. Once a successful approach was derived, this was used on 19 live rats under anesthesia. Fourteen rats had a 1-minute facial nerve crush performed, and 5 had a sham surgery with complete surgical exposure of the facial nerve but no crush. Rats were followed for a 12-week duration evaluating immediate postoperative facial nerve function, complications, and survival. RESULTS: All 14 (100%) rats that underwent surgery with crush injury had complete facial paralysis postoperatively. Complete facial paralysis was defined as loss of eye-blink reflex, flat vibrissae, and lack of vibrissae movement. The 5 sham surgery rats had complete facial function postoperatively. Surgery was performed by 2 separate surgeons with no difference in outcome between the 2. Complications occurred in only 1 animal (1/19, 5.3%), which was a corneal abrasion requiring sacrifice. CONCLUSION: Our group describes a consistent method for performing an intracranial crush injury in the rat. This new model and its applications in translational facial nerve research are promising, particularly with tumors or lesions at the cerebellopontine angle. PMID- 22049022 TI - Rapid degradation of cyclooxygenase-1 and hematopoietic prostaglandin D synthase through ubiquitin-proteasome system in response to intracellular calcium level. AB - Cyclooxygenase (COX)-1 and hematopoietic prostaglandin (PG) D synthase (H-PGDS) proteins, which are both involved in the arachidonate cascade, were stable in human megakaryocytic MEG-01 cells. In contrast, once the intracellular calcium level was increased by treatment with a calcium ionophore, both protein levels rapidly decreased with a half-life of less than 30 and 120 min for COX-1 and H PGDS, respectively. In the presence of a proteasome inhibitor, COX-1 and H-PGDS proteins accumulated within 10 and 30 min, respectively, and concurrently appeared as the high-molecular-mass ubiquitinated proteins within 30 and 60 min, respectively, after an increase in the intracellular calcium level. The ubiquitination of these proteins was also observed when ADP, instead of a calcium ionophore, was used as an inducer to elevate the intracellular calcium level. When the entry of calcium ion into the cells was inhibited by ethylene glycol tetraacetic acid (EGTA), the ubiquitination of COX-1 and H-PGDS was clearly suppressed; and the addition of CaCl(2) to the medium cleared the EGTA-mediated suppression of the ubiquitination. These results indicate that COX-1 and H-PGDS were rapidly ubiquitinated and degraded through the ubiquitin-proteasome system in response to the elevation of the intracellular calcium level. PMID- 22049023 TI - Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex. AB - Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development. PMID- 22049024 TI - Gap junction assembly: roles for the formation plaque and regulation by the C terminus of connexin43. AB - Using an established gap junction (GJ) assembly system with experimentally reaggregated cells, we analyzed "formation plaques" (FPs), apparent sites of GJ assembly. Employing freeze-fracture electron microscopy methods combined with filipin labeling of sterols and immunolabeling for connexin43 (Cx43), we demonstrated that FPs constitute distinct membrane "domains" and that their characteristic 10-nm particles contain connexin43, thus representing precursors (i.e., GJ hemichannels) engaged in assembly. Analysis of FPs in new systems-HeLa and N2A cells-resolved questions surrounding several key but poorly understood steps in assembly, including matching of FP membranes in apposed cells, reduction in the separation between FP membranes during assembly, and the process of particle aggregation. Findings also indicated that "docking" of GJ hemichannels occurs within FP domains and contributes to reduction of intermembrane separation between FPs. Other experiments demonstrated that FPs develop following a major C terminal truncation of Cx43 (M257), although assembly was delayed. Particle aggregation also occurred at lower densities, and densities of particles within developing GJ aggregates failed to achieve full-length levels. With regard to regulation, inhibition of assembly following protein kinase C activation failed to occur in the M257 truncation mutants, as measured by intercellular dye transfer. However, several C-terminal serine mutations failed to disrupt inhibition. PMID- 22049025 TI - An association between type Igamma PI4P 5-kinase and Exo70 directs E-cadherin clustering and epithelial polarization. AB - E-Cadherin-mediated formation of adherens junctions (AJs) is essential for the morphogenesis of epithelial cells. However, the mechanisms underlying E-cadherin clustering and AJ maturation are not fully understood. Here we report that type Igamma phosphatidylinositol-4-phosphate 5-kinase (PIPKIgamma) associates with the exocyst via a direct interaction with Exo70, the exocyst subunit that guides the polarized targeting of exocyst to the plasma membrane. By means of this interaction, PIPKIgamma mediates the association between E-cadherin and Exo70 and determines the targeting of Exo70 to AJs. Further investigation revealed that Exo70 is necessary for clustering of E-cadherin on the plasma membrane and extension of nascent E-cadherin adhesions, which are critical for the maturation of cohesive AJs. In addition, we observed phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)) accumulation at E-cadherin clusters during the assembly of E-cadherin adhesions. PIPKIgamma-generated PI4,5P(2) is required for recruiting Exo70 to newly formed E-cadherin junctions and facilitates the assembly and maturation of AJs. These results support a model in which PIPKIgamma and PIPKIgamma-generated PI4,5P(2) pools at nascent E-cadherin contacts cue Exo70 targeting and orient the tethering of exocyst-associated E-cadherin. This could be an important mechanism that regulates E-cadherin clustering and AJ maturation, which is essential for the establishment of solid, polarized epithelial structures. PMID- 22049026 TI - Several RNase T2 enzymes function in induced tRNA and rRNA turnover in the ciliate Tetrahymena. AB - RNase T2 enzymes are produced by a wide range of organisms and have been implicated to function in diverse cellular processes, including stress-induced anticodon loop cleavage of mature tRNAs to generate tRNA halves. Here we describe a family of eight RNase T2 genes (RNT2A-RNT2H) in the ciliate Tetrahymena thermophila. We constructed strains lacking individual or combinations of these RNT2 genes that were viable but had distinct cellular and molecular phenotypes. In strains lacking only one Rnt2 protein or lacking a subfamily of three catalytically inactive Rnt2 proteins, starvation-induced tRNA fragments continued to accumulate, with only a minor change in fragment profile in one strain. We therefore generated strains lacking pairwise combinations of the top three candidates for Rnt2 tRNases. Each of these strains showed a distinct starvation specific profile of tRNA and rRNA fragment accumulation. These results, the delineation of a broadened range of conditions that induce the accumulation of tRNA halves, and the demonstration of a predominantly ribonucleoprotein-free state of tRNA halves in cell extract suggest that ciliate tRNA halves are degradation intermediates in an autophagy pathway induced by growth arrest that functions to recycle idle protein synthesis machinery. PMID- 22049027 TI - Mycetoma. PMID- 22049028 TI - A 45-year-old farmer with an ulcerative rash, shock, and hemorrhagic meningitis. PMID- 22049029 TI - Efficacy and safety of artemether-lumefantrine in the treatment of acute, uncomplicated Plasmodium falciparum malaria: a pooled analysis. AB - Randomized trials have confirmed the efficacy and safety of artemether lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria. Data from seven studies supported by Novartis (1996-2007), including 647 adults (> 16 years of age, 83.3% completed the study) and 1,332 children (<= 16 years of age, 89.3% completed the study) with microscopically confirmed uncomplicated P. falciparum malaria and treated with the recommended regimen of AL, were pooled. The 28-day polymerase chain reaction-corrected parasitologic cure rate (primary efficacy endpoint) was 97.1% (495 of 510) in adults and 97.3% (792 of 814) in children (evaluable population). Gametocytemia prevalence after day was 4.2% (23 of 554) in adults and 0.9% (8 of 846) in children. No noteworthy safety signals were observed. Serious adverse events occurred in 1.4% of the adults and 1.3% of the children. This study is the largest data set to date assessing AL therapy for treatment of acute uncomplicated P. falciparum malaria. Artemether-lumefantrine showed high cure rates and rapid resolution of parasitemia, fever, and gametocytemia in adults and children, and showed an excellent safety and tolerability profile. PMID- 22049030 TI - Occupational activities associated with a reported history of malaria among women working in small-scale agriculture in South Africa. AB - Malaria-endemic agricultural communities are at risk for this disease because of crop and agricultural activities. A cross-sectional survey among women in small scale agriculture on irrigated and dryland areas in Makhatini Flats, KwaZulu Natal South Africa explored associations with self-reported history of malaria, including demographics, crop production, and specific agricultural activities. Ninety-eight (15.2%) of 644 women reported malaria while working in agriculture. More women working in drylands than women working in irrigation scheme reported disease (18.4% versus 10.9%; P < 0.05). Working self or family-owned farms (prevalence ratio [PR] = 2.6, 95% confidence interval [CI] = 1.3-5.2), spraying pesticides (PR = 2.3; 95% CI = 1.4-3.8), cultivating sugar cane (PR = 1.6, 95% CI = 1.1-2.3), and cultivating cotton and mangoes (PR = 1.7, 95% CI = 1.1-2.6) were positively associated with a history of malaria while working in agriculture. This study suggests that certain agricultural activities and types of crop production may increase the risk for malaria among women working in small-scale agriculture. PMID- 22049031 TI - Distribution pattern of Plasmodium falciparum chloroquine transporter (pfcrt) gene haplotypes in Sri Lanka 1996-2006. AB - Widespread antimalarial resistance has been a barrier to malaria elimination efforts in Sri Lanka. Analysis of genetic markers in historic parasites may uncover trends in the spread of resistance. We examined the frequency of Plasmodium falciparum chloroquine transporter (pfcrt; codons 72-76) haplotypes in Sri Lanka in 1996-1998 and 2004-2006 using a high-resolution melting assay. Among 59 samples from 1996 to 1998, we detected the SVMNT (86%), CVMNK (10%), and CVIET (2%) haplotypes, with a positive trend in SVMNT and a negative trend in CVMNK frequency (P = 0.004) over time. Among 24 samples from 2004 to 2006, we observed only the SVMNT haplotype. This finding indicates selection for the SVMNT haplotype over time and its possible fixation in the population. PMID- 22049032 TI - Nuclear magnetic resonance: a tool for malaria diagnosis? AB - Malaria control can be improved by rapid, sensitive, low-cost detection of infection. Several such strategies are being pursued. Rapid diagnostic tests can detect infections at parasite densities above 200 MUL(-1). Polymerase chain reaction methods can detect low parasite densities, but are slow and prone to contamination under field conditions. Methods that detect hemozoin presence in blood have been proposed as alternatives for rapid detection of infection. In this study, we used a benchtop nuclear magnetic resonance (NMR) device to detect hemozoin. This device could be deployed in malaria-endemic settings. We measured synthetic hemozoin in phosphate-buffered saline and malaria parasites in human blood. The NMR detected hemozoin in suspensions of 4 ng MUL(-1) and parasites at densities of 8,000-10,000 MUL(-1) (0.2% parasitemia). Thus, our preliminary NMR approach, although providing very rapid measurements, is unlikely to achieve the required sensitivity and specificity for malaria diagnosis, unless a preliminary concentration step is performed. PMID- 22049033 TI - Can we use a lower dose of liposomal amphotericin B for the treatment of mucosal American leishmaniasis? AB - Liposomal amphotericin B has been used as an alternative treatment of mucosal leishmaniasis, but the optimal dose is not established. We retrospectively reviewed the clinical outcome of eight patients with mucosal leishmaniasis treated with liposomal amphotericin B. The mean total dose was 35 mg/kg (range 24 50 mg/kg), which resulted in the healing of all the lesions in all patients and no recurrences were observed during the follow-up period (mean 25 months; range 7 40 months). PMID- 22049034 TI - Epidemiology of leishmaniasis in Spain based on hospitalization records (1997 2008). AB - All the records from the Spanish information system for hospital data of patients diagnosed with leishmaniasis during a 12-year period (1997-2008) were studied. The 2,028 individuals were hospitalized because of leishmaniasis, as indicated by the principal diagnostic code. The average hospitalization rate was 0.41/100,000 inhabitants. One-third of them were co-infected with human immunodeficiency virus (HIV). The incidence of hospitalization in the adult population with leishmaniasis co-infected with HIV increased with age, peaked at 35-39 years of age and subsequently declined. In the pediatric population, all leishmaniasis cases occurred in HIV-negative children. Incidence of hospitalizations was highest in Madrid and in the Mediterranean coast. The cost per inpatient hospital care was $9,601 corresponding to an annual direct cost of more than $1.5 million for inpatient care alone. The economical burden of leishmaniasis is not neglectable and in the 12-year study period it represented more than $19 million. PMID- 22049035 TI - Costs of integrated mass drug administration for neglected tropical diseases in Haiti. AB - We conducted a cost analysis of Haiti's Ministry of Public Health and Population neglected tropical disease program, Projet des Maladies Tropicales Negligees and collected data for 9 of 55 communes participating in the May 2008-April 2009 mass drug administration (MDA). The Projet des Maladies Tropicales Negligees Program partnered with IMA World Health and Hopital Ste. Croix to implement MDA for treatment of lymphatic filariasis and soil-transmitted helminthiasis by using once a year treatment with albendazole and diethylcarbamazine in a population of approximately 8 million persons. Methods included analyzing partner financial records and conducting retrospective surveys of personnel. In the nine communes, 633,261 persons were treated at a cost of U.S. $0.64 per person, which included the cost of donated drugs, and at a cost of U.S. $0.42 per person treated, when excluding donated drug costs. The MDA for lymphatic filariasis in Haiti began in 2000, with the treatment of 105,750 persons at a cost per person of U.S. $2.23. The decrease in cost per person treated is the result of cumulative implementation experience and economies of scale. PMID- 22049036 TI - Genotypic characterization of Cryptosporidium hominis from water samples in Sao Paulo, Brazil. AB - The protozoan parasite Cryptosporidium has emerged as one of the most important water contaminants, causing waterborne outbreaks of diarrheal diseases worldwide. The small size of oocysts under the microscope and the possibility of changes in characteristics of oocysts, mainly in environmental samples, make the taxonomy of the genus difficult if morphologic characteristics are considered. This limitation encouraged the application of molecular methods to identify this microorganism. The aim of this study was to detect and identify by nested polymerase chain reaction oocysts of Cryptosporidium present in water samples in the state of Sao Paulo, Brazil. Water samples were concentrated through a membrane filter, DNA was extracted by using a standard technique, and both amplification reactions used forward and reverse oligonucleotides that were complementary to Cryptosporidium 18S ribosomal RNA gene sequences. Thirty water samples from different sites of collection in the state of Sao Paulo were evaluated. Cryptosporidium oocysts were detected in 30% of the samples. By genoptyping, C. hominis and Cryptosporidium sp. were identified in recreational water and C. meleagridis was identified in surface water samples. This is the first report of C. hominis in environmental samples in Brazil. Although identification of Cryptosporidium is still a difficult task, molecular methods are essential for specific identification and are a helpful tool to aid to understand the epidemiology of this parasite in Brazil. PMID- 22049037 TI - Current knowledge of Leishmania vectors in Mexico: how geographic distributions of species relate to transmission areas. AB - Leishmaniases are a group of vector-borne diseases with different clinical manifestations caused by parasites transmitted by sand fly vectors. In Mexico, the sand fly Lutzomyia olmeca olmeca is the only vector proven to transmit the parasite Leishmania mexicana to humans, which causes leishmaniasis. Other vector species with potential medical importance have been obtained, but their geographic distributions and relation to transmission areas have never been assessed. We modeled the ecological niches of nine sand fly species and projected niches to estimate potential distributions by using known occurrences, environmental coverages, and the algorithms GARP and Maxent. All vector species were distributed in areas with known recurrent transmission, except for Lu. diabolica, which appeared to be related only to areas of occasional transmission in northern Mexico. The distribution of Lu. o. olmeca does not overlap with all reported cutaneous leishmaniasis cases, suggesting that Lu. cruciata and Lu. shannoni are likely also involved as primary vectors in those areas. Our study provides useful information of potential risk areas of leishmaniasis transmission in Mexico. PMID- 22049038 TI - Phlebotomine vector ecology in the domestic transmission of American cutaneous leishmaniasis in Chaparral, Colombia. AB - Phlebotomine vector ecology was studied in the largest recorded outbreak of American cutaneous leishmaniasis in Colombia in 2004. In two rural townships that had experienced contrasting patterns of case incidence, this study evaluated phlebotomine species composition, seasonal abundance, nocturnal activity, blood source, prevalence of Leishmania infection, and species identification. CDC miniature light traps were used to trap the phlebotomines. Traps were set indoors, peridomestically, and in woodlands. Natural infection was determined in pools by polymerase chain reaction-Southern blot, and blood sources and species identification were determined by sequencing. Large differences were observed in population abundance between the two townships evaluated. Lutzomyia longiflocosa was the most abundant species (83.1%). Abundance was higher during months with lower precipitation. Nocturnal activity was associated with human domestic activity. Blood sources identified were mainly human (85%). A high prevalence of infection was found in L. longiflocosa indoors (2.7%) and the peridomestic setting (2.5%). L. longiflocosa was responsible for domestic transmission in Chaparral. PMID- 22049039 TI - Mitochondrial DNA detects a complex evolutionary history with Pleistocene Epoch divergence for the neotropical malaria vector Anopheles nuneztovari sensu lato. AB - Cryptic species and lineages characterize Anopheles nuneztovari s.l. Gabaldon, an important malaria vector in South America. We investigated the phylogeographic structure across the range of this species with cytochrome oxidase subunit I (COI) mitochondrial DNA sequences to estimate the number of clades and levels of divergence. Bayesian and maximum-likelihood phylogenetic analyses detected four groups distributed in two major monophyletic clades (I and II). Samples from the Amazon Basin were clustered in clade I, as were subclades II-A and II-B, whereas those from Bolivia/Colombia/Venezuela were restricted to one basal subclade (II C). These data, together with a statistical parsimony network, confirm results of previous studies that An. nuneztovari is a species complex consisting of at least two cryptic taxa, one occurring in Colombia and Venezuela and the another occurring in the Amazon Basin. These data also suggest that additional incipient species may exist in the Amazon Basin. Divergence time and expansion tests suggested that these groups separated and expanded in the Pleistocene Epoch. In addition, the COI sequences clearly separated An. nuneztovari s.l. from the closely related species An. dunhami Causey, and three new records are reported for An. dunhami in Amazonian Brazil. These findings are relevant for vector control programs in areas where both species occur. Our analyses support dynamic geologic and landscape changes in northern South America, and infer particularly active divergence during the Pleistocene Epoch for New World anophelines. PMID- 22049040 TI - Tropical skin infections among Israeli travelers. AB - Infectious skin disorders are common dermatologic illnesses in travelers. Knowledge of post-travel-related infectious skin disorders will allow for effective pre- and post-travel counseling. All cases of returning travelers seen in our center seeking care for infectious skin diseases were included in this study. For a comparison, data on returned travelers with non-infectious skin diseases and healthy travelers who had pre-travel consultations in our institution were also analyzed. Altogether, skin-related diagnosis was reported in 540 ill travelers, and among them, 286 (53%) had infectious skin diseases. Tropical skin infection was diagnosed in 64% of the infectious cases. Travelers returning from Latin America were significantly more ill with tropical skin infections than those traveling to Asia and Africa, The most common diagnoses were cutaneous leishmaniasis, myiasis, and cutaneous larva migrans. In conclusion, tropical skin infections are common among Israeli travelers, especially among those who visited Latin America. PMID- 22049041 TI - A comparative study of hepatitis caused by scrub typhus and viral hepatitis A in South Korea. AB - We compared clinical features and laboratory findings of 104 patients with hepatitis A and 197 patients with scrub typhus. Nausea, vomiting, abdominal pain, hepatomegaly, and jaundice were common in patient with hepatitis A, and fever and headache were significantly more common in patients with scrub typhus. At presentation, an alanine aminotransferase (ALT) level >= 500 U/L was observed in 1% of scrub typhus patients and in 87.5% of hepatitis A patients (P < 0.001). A bilirubin level >= 1.3 mg/dL was observed in 16.8% of scrub typhus patients and 90.4% of hepatitis A patients. The ALT:lactate dehydrogenase ratio was <= 5 in 97.4% of the patients with scrub typhus and > 5 in 95.2% of those with hepatitis A (P < 0.001). Fever, headache, rash, and eschar are findings that indicate scrub typhus. An ALT level >= 500 U/L (adjusted odds ratio = 0.011) a bilirubin level >= 1.3 (adjusted odds ratio = 0.024), an ALT:lactate dehydrogenase ratio > 5, and hepatomegaly are indications of viral hepatitis A. PMID- 22049042 TI - Human pentastomiasis caused by Armillifer moniliformis in Malaysian Borneo. AB - We report a case of visceral pentastomiasis caused by Armillifer moniliformis in a 70-year-old aboriginal farmer from rural Malaysian Borneo. The patient complained of upper abdominal pain, jaundice, and loss of weight. Radiological investigations and subsequent histopathological examination revealed an adenocarcinoma of the pancreas with an adjacent liver nodule containing a nymph of A. moniliformis. This report constitutes the first documented human pentastomid infection in the whole of Malaysia after nearly 40 years, and it is the third description from Malaysian Borneo. Cases of human and animal pentastomiasis in Malaysia are discussed. PMID- 22049043 TI - Using child health outcomes to identify effective measures of handwashing. AB - We assessed which practical handwashing indicators were independently associated with reduced child diarrhea or respiratory disease. Fieldworkers collected 33 indicators of handwashing at baseline in 498 households in 50 villages in rural Bangladesh. Community monitors visited households monthly and asked standard questions about diarrhea and symptoms of respiratory illness among children under 5 years of age. In multivariate analysis, three handwashing indicators were independently associated with less child diarrhea-mothers reporting usually washing hands with soap before feeding a child, mothers using soap when asked to show how they usually washed their hands after defecation, and children having visibly clean finger pads. Two indicators were independently associated with fewer respiratory infections-mothers allowing their hands to air dry after the handwashing demonstration and the presence of water where the respondents usually wash hands after defecation. These rapid handwashing indicators should be considered for inclusion in handwashing assessments. PMID- 22049044 TI - Evidence for genetic susceptibility to developing early childhood diarrhea among shantytown children living in northeastern Brazil. AB - To explore the genetic components of susceptibility to early childhood diarrhea (ECD), we used a quantitative genetic approach to estimate the heritability of ECD among children from two Brazilian favelas. Shared environment was used to model common exposure to environmental factors. Genetic relatedness was determined from pedigree information collected by screening household participants (n = 3,267) from two geographically related favelas located in Fortaleza, Brazil. There were 277 children within these pedigrees for whom diarrheal episodes in the first two years of life were recorded. Data on environmental exposure and pedigree relationship were combined to quantitatively partition phenotypic variance in ECD into environmental and genetic components by using a variance components approach as implemented in Sequential Oligogenic Linkage Analysis Routines program. Heritability accounted for 54% of variance in ECD and proximity of residence effect accounted for 21% (P < 0.0001). These findings suggest a substantial genetic component to ECD susceptibility and the potential importance of future genetics studies. PMID- 22049045 TI - A cutaneous ulcer resulting from Mycobacterium ulcerans--Leishmania braziliensis coinfection in South America. AB - Buruli ulcer is a tropical skin disease caused by Mycobacterium ulcerans. Its mode of transmission is not yet clearly understood. We report here a cutaneous ulcer in a European traveler in South America resulting from a coinfection detected specifically for Mycobacterium ulcerans and Leishmania braziliensis DNA with real-time polymerase chain reaction. This observation of a unique cutaneous ulcer raises the issue about possible modes of transmission of those two pathogens by the same vector. PMID- 22049046 TI - Combining PCR with microscopy to reduce costs of laboratory diagnosis of Buruli ulcer. AB - The introduction of antibiotic therapy as first-line treatment of Buruli ulcer underlines the importance of laboratory confirmation of clinical diagnosis. Because smear microscopy has very limited sensitivity, the technically demanding and more expensive IS2404 diagnostic polymerase chain reaction (PCR) has become the main method for confirmation. By optimization of the release of mycobacteria from swab specimen and concentration of bacterial suspensions before smearing, we were able to improve the detection rate of acid-fast bacilli by microscopy after Ziehl-Neelsen staining. Compared with IS2404 PCR, which is the gold standard diagnostic method, the sensitivity and specificity of microscopy with 100 concentrated specimens were 58.4% and 95.7%, respectively. We subsequently evaluated a stepwise laboratory confirmation algorithm with detection of AFB as first-line method and IS2404 PCR performed only with those samples that were negative in microscopic analysis. This stepwise approach reduced unit cost by more than 50% to $5.41, and the total costs were reduced from $917 to $433. PMID- 22049047 TI - In vitro and in vivo activity of first generation cephalosporins against Leptospira. AB - Third generation cephalosporins are commonly used in the treatment of leptospirosis. The efficacy of first generation cephalosporins has been less well studied. Susceptibility testing of 13 Leptospira strains (11 serovars) to cefazolin and cephalexin was conducted using broth microdilution. Median minimal inhibitory concentration (MIC) for cefazolin and cephalexin ranged from < 0.016 to 2 MUg/mL (MIC(90) = 0.5 MUg/mL) and from 1 to 8 MUg/mL (MIC(90) = 8 MUg/mL), respectively. Efficacy of cefazolin and cephalexin in an acute lethal hamster model of leptospirosis was studied. Survival rates for cefazolin were 80%, 100%, and 100%, and survival rates for cephalexin were 50%, 80%, and 100% (treated with 5, 25, and 50 mg/kg per day for 5 days, respectively). Each treatment group showed improved survival compared with no treatment (P < 0.01), and none of the therapies, regardless of dose, was statistically significantly different than doxycycline. These results support a potential role for first generation cephalosporins as alternative therapies for leptospirosis. PMID- 22049048 TI - Challenges of establishing the correct diagnosis of outbreaks of acute febrile illnesses in Africa: the case of a likely Brucella outbreak among nomadic pastoralists, northeast Kenya, March-July 2005. AB - An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed. PMID- 22049049 TI - Anemia and Helicobacter pylori seroreactivity in a rural Haitian population. AB - Anemia is a significant health concern worldwide and can be the result of nutritional, environmental, social, and infectious etiologies. We estimated the prevalence of anemia in 336 pre-school children and 132 adults in the rural Central Plateau of Haiti and assessed associations with age, sex, household size, water source, sanitation, and Helicobacter pylori seroreactivity using logistic regression analysis; 80.1% (269/336) of children and 63.6% (84/132) of adults were anemic. Among children, younger age was associated with increased prevalence of anemia (adjusted odds ratio [aOR] = 4.1, 95% confidence interval [CI] = 1.5 11.1 for children 6-11 months compared with children 48-59 months). Among adults, 50.8% were H. pylori-seropositive, and seropositivity was inversely associated with anemia (aOR = 0.4, 95% CI = 0.2-0.9). Anemia prevalence in this region of Haiti is very high and not attributable to sanitary conditions or a high prevalence of H. pylori infection. PMID- 22049050 TI - Spotted fever group rickettsiae in ticks collected from wild animals in Israel. AB - We report molecular evidence for the presence of spotted fever group rickettsiae (SFGR) in ticks collected from roe deer, addax, red foxes, and wild boars in Israel. Rickettsia aeschlimannii was detected in Hyalomma marginatum and Hyalomma detritum while Rickettsia massiliae was present in Rhipicephalus turanicus ticks. Furthermore, a novel uncultured SFGR was detected in Haemaphysalis adleri and Haemaphysalis parva ticks from golden jackals. The pathogenicity of the novel SFGR for humans is unknown; however, the presence of multiple SFGR agents should be considered when serological surveillance data from Israel are interpreted because of significant antigenic cross-reactivity among Rickettsia. The epidemiology and ecology of SFGR in Israel appear to be more complicated than was previously believed. PMID- 22049051 TI - Severity predictors in eschar-positive scrub typhus and role of serum osteopontin. AB - We prospectively evaluated severity predictors in terms of host, microorganism, and treatment factors in 153 eschar-positive scrub typhus patients. Severity was assessed with the Acute Physiology and Chronic Health Evaluation (APACHE) II score (< 10 versus >= 10) and predefined criteria of severe complications. Genotypes of Orientia tsutsugamushi were determined. Independent risk factors for severity (APACHE II score >= 10) were old age, diabetes mellitus, serum osteopontin > 100 ng/mL, and a group of underlying diseases (congestive heart failure, cerebrovascular disease, chronic liver disease, bronchial asthma, and chronic obstructive lung diseases). Anemia (<= 10 g/dL) and C-reactive protein > 10 mg/dL were indicators of current severity. Neither the delay in antibiotics administration nor strain types (Boryong, Taguchi, or Kanda/Kawasaki) contributed to the severity. The risk factors for severe complications were similar. Serum osteopontin > 100 ng/mL had a negative predictive value of 96% for severe complications. This marker can be used to rule out severe disease status. PMID- 22049052 TI - Molecular detection of Rickettsia felis, Bartonella henselae, and B. clarridgeiae in fleas from domestic dogs and cats in Malaysia. AB - The presence of Rickettsia felis, Bartonella henselae and B. clarridgeiae in 209 fleas (Ctenocephalides felis) obtained from domestic cats and dogs in several locations in Malaysia was investigated in this study. Using a polymerase chain reaction specific for the citrate synthase (gltA) and 17-kD antigenic protein (17kD) genes of rickettsiae, we detected R. felis DNA in 6 (2.9%) fleas. For detection of bartonellae, amplification of the heme-binding protein (pap31) and riboflavin synthase (ribC) genes identified B. henselae and B. clarridgeiae DNA in 24 (11.5%) and 40 (19.1%) fleas, respectively. The DNA of B. henselae and B. clarridgeiae was detected in 10 (4.8%) fleas. Two B. henselae genogroups (Marseille and Houston-1) were detected in this study; genogroup Marseille (genotype Fizz) was found more often in the fleas. The findings in this study suggest fleas as potential vectors of rickettsioses and cat-scratch disease in this country. PMID- 22049053 TI - Imported acquired immunodeficiency syndrome-related histoplasmosis in metropolitan France: a comparison of pre-highly active anti-retroviral therapy and highly active anti-retroviral therapy eras. AB - Histoplasma capsulatum var. capsulatum infection is rare outside disease-endemic areas. Clinical presentation and outcome of acquired immunodeficiency syndrome related histoplasmosis are unknown in non-endemic areas with wide access to highly active anti-retroviral therapy (HAART). Retrospective analysis of cases recorded at the French National Reference Center for Mycoses and Antifungals during two decades: pre-HAART (1985-1994) and HAART (1997-2006). Clinical features and outcome of all adults with proven acquired immunodeficiency syndrome related histoplasmosis were compared between the two periods. One hundred four patients were included (40 during the pre-HAART era and 64 during the HAART era). Diagnosis was established a mean of 62 days after onset of symptoms. One-year overall mortality rates decreased from 53% (pre-HAART era) to 22% (HAART era). Diagnosis during the pre-HAART era and an older age were the only independent factors associated with death. Histoplasmosis is a rare invasive fungal infection outside disease-endemic areas. Its prognosis improved significantly during the HAART era. PMID- 22049054 TI - Validation of probability equation and decision tree in predicting subsequent dengue hemorrhagic fever in adult dengue inpatients in Singapore. AB - We developed a probability equation and a decision tree from 1,973 predominantly dengue serotype 1 hospitalized adult dengue patients in 2004 to predict progression to dengue hemorrhagic fever (DHF), applied in our clinic since March 2007. The parameters predicting DHF were clinical bleeding, high serum urea, low serum protein, and low lymphocyte proportion. This study validated these in a predominantly dengue serotype 2 cohort in 2007. The 1,017 adult dengue patients admitted to Tan Tock Seng Hospital, Singapore had a median age of 35 years. Of 933 patients without DHF on admission, 131 progressed to DHF. The probability equation predicted DHF with a sensitivity (Sn) of 94%, specificity (Sp) 17%, positive predictive value (PPV) 16%, and negative predictive value (NPV) 94%. The decision tree predicted DHF with a Sn of 99%, Sp 12%, PPV 16%, and NPV 99%. Both tools performed well despite a switch in predominant dengue serotypes. PMID- 22049055 TI - Pteropid bats are confirmed as the reservoir hosts of henipaviruses: a comprehensive experimental study of virus transmission. AB - Bats of the genus Pteropus have been identified as the reservoir hosts for the henipaviruses Hendra virus (HeV) and Nipah virus (NiV). The aim of these studies was to assess likely mechanisms for henipaviruses transmission from bats. In a series of experiments, Pteropus bats from Malaysia and Australia were inoculated with NiV and HeV, respectively, by natural routes of infection. Despite an intensive sampling strategy, no NiV was recovered from the Malaysian bats and HeV was reisolated from only one Australian bat; no disease was seen. These experiments suggest that opportunities for henipavirus transmission may be limited; therefore, the probability of a spillover event is low. For spillover to occur, a range of conditions and events must coincide. An alternate assessment framework is required if we are to fully understand how this reservoir host maintains and transmits not only these but all viruses with which it has been associated. PMID- 22049056 TI - West nile virus (Kunjin subtype) disease in the northern territory of Australia- a case of encephalitis and review of all reported cases. AB - West Nile virus Kunjin subtype (WNV/KUNV) is enzootic across the tropical north of Australia, with epizootic spread into other jurisdictions. The clinical spectrum of illness in humans is poorly described. We report a clinical case of WNV/KUNV encephalitis and performed a retrospective chart audit of all cases of WNV/KUNV notified in the Northern Territory from 1992 to 2010. Thirteen cases of WNV/KUNV disease were identified; case notes were available for 10 of these presentations. Six of these patients had confirmed infection and presented with neuroinvasive illness, whereas the other four suspect cases comprised three cases with arthralgia, myalgia, and/or rash and one case with fever alone. On the available evidence, WNV/KUNV is of lower virulence compared with the New York 1999 strain. Difficulties in serological diagnosis, especially when paired acute and convalescent sera are not available, may adversely impact the accuracy of the epidemiological and clinical understanding of this virus. PMID- 22049057 TI - Rotavirus prevalence in the primary care setting in Nicaragua after universal infant rotavirus immunization. AB - Nicaragua was the first developing nation to implement universal infant rotavirus immunization with the pentavalent rotavirus vaccine (RV5). Initial studies of vaccine effectiveness in Nicaragua and other developing nations have focused on the prevention of hospitalizations and severe rotavirus diarrhea. However, rotavirus diarrhea is more commonly treated in the primary care setting, with only 1-3% of rotavirus cases receiving hospital care. We measured the prevalence of rotavirus infection in primary care clinics in Leon, Nicaragua, after introduction of the immunization program. In the post-vaccine period, 3.5% (95% confidence interval = 1.9-5.8) of children seeking care for diarrhea tested positive for rotavirus. A high diversity of rotavirus genotypes was encountered among the few positive samples. In conclusion, rotavirus was an uncommon cause of childhood diarrhea in this primary care setting after implementation of a rotavirus immunization program. PMID- 22049058 TI - Dual infection of novel influenza viruses A/H1N1 and A/H3N2 in a cluster of Cambodian patients. AB - During the early months of 2009, a novel influenza A/H1N1 virus (pH1N1) emerged in Mexico and quickly spread across the globe. In October 2009, a 23-year-old male residing in central Cambodia was diagnosed with pH1N1. Subsequently, a cluster of four influenza-like illness cases developed involving three children who resided in his home and the children's school teacher. Base composition analysis of internal genes using reverse transcriptase polymerase chain reaction and electrospray ionization mass spectrometry revealed that specimens from two of the secondary victims were coinfected with influenza A/H3N2 and pH1N1. Phylogenetic analysis of the hemagglutinin genes from these isolated viruses showed that they were closely related to existing pH1N1 and A/H3N2 viruses circulating in the region. Genetic recombination was not evident within plaque purified viral isolates on full genome sequencing. This incident confirms dual influenza virus infections and highlights the risk of zoonotic and seasonal influenza viruses to coinfect and possibly, reassort where they cocirculate. PMID- 22049059 TI - Phthalates induce proliferation and invasiveness of estrogen receptor-negative breast cancer through the AhR/HDAC6/c-Myc signaling pathway. AB - The environmentally present group of chemical phthalates, or phthalate esters, has been recognized as a rising threat to public health, including cancer. While most studies have addressed the estrogenic effects of phthalates in malignancies of the breast and the prostate, little is known about their role in the etiology of hormone-independent cancer. Here we show that treatments with the phthalates n butyl benzyl phthalate (BBP) and dibutyl phthalate (DBP) at 1 MUM induced proliferation (BBP, 3.2-fold; DBP, 3.2-fold), migration (BBP, 2.6-fold; DBP, 2.6 fold), invasion (BBP, 2.7-fold; DBP, 3.1-fold), and tumor formation (EC(50): BBP, 0.12 MUM; DBP, 0.22 MUM) in estrogen receptor (ER)-negative breast cancer cells (MDA-MB-231). We further demonstrate that phthalates stimulated the cell surface aryl hydrocarbon receptor (AhR) and triggered the downstream cyclic AMP (cAMP) PKA-CREB1 signaling cascade. The pathway led to increased expression of HDAC6, which facilitated nuclear assembly of the beta-catenin-LEF1/TCF4 transcriptional complex and transactivation of the c-Myc oncogene. This nongenomic pathway emanated from the phthalate-induced AhR promoted tumorigenesis of ER-negative breast cancer. Collectively, our findings revealed a novel oncogenic mechanism of phthalates in breast cancer independent from their estrogenic activities. PMID- 22049060 TI - Loss of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) induces apoptotic processes in pancreatic carcinoma cells. AB - Early invasive growth and metastasis are features of pancreatic cancer that rely on its resistance to anoikis, an apoptosis program activated on loss of matrix anchorage. How anoikis is regulated is unclear. UDP-N-acetylglucosamine-2 epimerase/N-acetylmannosamine-kinase (GNE) was silenced, or p16 was overexpressed, in human pancreatic carcinoma cells. Gene expression profiling, enzymatic assays, Western blotting, and cell cycle analysis were conducted. Silencing of GNE, the key enzyme of sialic acid biosynthesis, sensitizes pancreatic cancer cells to anoikis. Accordingly, we observed a loss of GNE enzyme activity in cells, which became anoikis susceptible after transfection with the tumor suppressor p16. Similarly, studies of another cell line with low GNE activity revealed strong anoikis susceptibility, confirming the association of low GNE activity and anoikis susceptibility. Gene expression profiling demonstrated that the loss of GNE triggered the transcriptional activation of the ATF4-ATF3-CHOP pathway, leading to apoptosis in the framework of the unfolded protein response. In silico analysis showed that GNE up-regulation occurred predominantly in pancreatic cancer but also in other malignancies. Delineation of GNE-dependent signaling pathways may provide targets that control anchorage dependence and/or restore drug efficacy, which is of utmost relevance for the treatment of pancreatic cancer. PMID- 22049061 TI - Misfolded proteins inhibit proliferation and promote stress-induced death in SV40 transformed mammalian cells. AB - Protein misfolding is implicated in neurodegenerative diseases and occurs in aging. However, the contribution of the misfolded ensembles to toxicity remains largely unknown. Here we introduce 2 primate cell models of destabilized proteins devoid of specific cellular functions and interactors, as bona fide misfolded proteins, allowing us to isolate the gain-of-function of non-native structures. Both GFP-degron and a mutant chloramphenicol-acetyltransferase fused to GFP (GFP Delta9CAT) form perinuclear aggregates, are degraded by the proteasome, and colocalize with and induce the chaperone Hsp70 (HSPA1A/B) in COS-7 cells. We find that misfolded proteins neither significantly compromise chaperone-mediated folding capacity nor induce cell death. However, they do induce growth arrest in cells that are unable to degrade them and promote stress-induced death upon proteasome inhibition by MG-132 and heat shock. Finally, we show that overexpression of all heat-shock factor-1 (HSF1) and Hsp70 proteins, as well as wild-type and deacetylase-deficient (H363Y) SIRT1, rescue survival upon stress, implying a noncatalytic action of SIRT1 in response to protein misfolding. Our study establishes a novel model and extends our knowledge on the mechanism of the function-independent proteotoxicity of misfolded proteins in dividing cells. PMID- 22049062 TI - State of the art in neuroprotection during acute type A aortic dissection repair. AB - Temporary (TND) or permanent neurologic dysfunctions (PND) represent the main neurological complications following acute aortic dissection repair. The aim of our experimental and clinical research was the improvement and update of the most common neuroprotective strategies which are in present use. HYPOTHERMIC CIRCULATORY ARREST (HCA): Cerebral metabolic suppression at the clinically most used temperatures (18-22 degrees C) is less complete than had been assumed previously. If used as a 'stand-alone' neuroprotective strategy, cooling to 15-20 degrees C with a jugular SO(2) >= 95% is needed to provide sufficient metabolic suppression. Regardless of the depth of cooling, the HCA interval should not exceed 25 min. After 40 min of HCA, the incidence of TND and PND increases, after 60 min, the mortality rate increases. ANTEGRADE SELECTIVE CEREBRAL PERFUSION (ASCP): At moderate hypothermia (25-28 degrees C), ASCP should be performed at a pump flow rate of 10ml/kg/min, targeting a cerebral perfusion pressure of 50 60mmHg. Experimental data revealed that these conditions offer an optimal regional blood flow in the cortex (80+/-27ml/min/100g), the cerebellum (77+/ 32ml/min/100g), the pons (89+/-5ml/min/100g) and the hippocampus (55+/ 16ml/min/100g) for 25 minutes. If prolonged, does ASCP at 32 degrees C provide the same neuroprotective effect? CANNULATION STRATEGY: Direct axillary artery cannulation ensures the advantage of performing both systemic cooling and ASCP through the same cannula, preventing additional manipulation with the attendant embolic risk. An additional cannulation of the left carotid artery ensures a bi hemispheric perfusion, with a neurologic outcome of only 6% TND and 1% PND. NEUROMONITORING: Near-infrared spectroscopy and evoked potentials may prove the effectiveness of the neuroprotective strategy used, especially if the trend goes to less radical cooling. CONCLUSION: A short interval of HCA (5 min) followed by a more extended period of ASCP (25 min) at moderate hypothermia (28 degrees C), with a pump flow rate of 10ml/kg/min and a cerebral perfusion pressure of 50 mmHg, represents safe conditions for open arch surgery. PMID- 22049063 TI - Intestinal adenocarcinomas in three generations of sheep. PMID- 22049064 TI - A dirichlet process prior for estimating lineage-specific substitution rates. AB - We introduce a new model for relaxing the assumption of a strict molecular clock for use as a prior in Bayesian methods for divergence time estimation. Lineage specific rates of substitution are modeled using a Dirichlet process prior (DPP), a type of stochastic process that assumes lineages of a phylogenetic tree are distributed into distinct rate classes. Under the Dirichlet process, the number of rate classes, assignment of branches to rate classes, and the rate value associated with each class are treated as random variables. The performance of this model was evaluated by conducting analyses on data sets simulated under a range of different models. We compared the Dirichlet process model with two alternative models for rate variation: the strict molecular clock and the independent rates model. Our results show that divergence time estimation under the DPP provides robust estimates of node ages and branch rates without significantly reducing power. Further analyses were conducted on a biological data set, and we provide examples of ways to summarize Markov chain Monte Carlo samples under this model. PMID- 22049065 TI - Pancrustacean phylogeny in the light of new phylogenomic data: support for Remipedia as the possible sister group of Hexapoda. AB - Remipedes are a small and enigmatic group of crustaceans, first described only 30 years ago. Analyses of both morphological and molecular data have recently suggested a close relationship between Remipedia and Hexapoda. If true, the remipedes occupy an important position in pancrustacean evolution and may be pivotal for understanding the evolutionary history of crustaceans and hexapods. However, it is important to test this hypothesis using new data and new types of analytical approaches. Here, we assembled a phylogenomic data set of 131 taxa, incorporating newly generated 454 expressed sequence tag (EST) data from six species of crustaceans, representing five lineages (Remipedia, Laevicaudata, Spinicaudata, Ostracoda, and Malacostraca). This data set includes all crustacean species for which EST data are available (46 species), and our largest alignment encompasses 866,479 amino acid positions and 1,886 genes. A series of phylogenomic analyses was performed to evaluate pancrustacean relationships. We significantly improved the quality of our data for predicting putative orthologous genes and for generating data subsets by matrix reduction procedures, thereby improving the signal to noise ratio in the data. Eight different data sets were constructed, representing various combinations of orthologous genes, data subsets, and taxa. Our results demonstrate that the different ways to compile an initial data set of core orthologs and the selection of data subsets by matrix reduction can have marked effects on the reconstructed phylogenetic trees. Nonetheless, all eight data sets strongly support Pancrustacea with Remipedia as the sister group to Hexapoda. This is the first time that a sister group relationship of Remipedia and Hexapoda has been inferred using a comprehensive phylogenomic data set that is based on EST data. We also show that selecting data subsets with increased overall signal can help to identify and prevent artifacts in phylogenetic analyses. PMID- 22049066 TI - The effects of alignment error and alignment filtering on the sitewise detection of positive selection. AB - When detecting positive selection in proteins, the prevalence of errors resulting from misalignment and the ability of alignment filters to mitigate such errors are not well understood, but filters are commonly applied to try to avoid false positive results. Focusing on the sitewise detection of positive selection across a wide range of divergence levels and indel rates, we performed simulation experiments to quantify the false positives and false negatives introduced by alignment error and the ability of alignment filters to improve performance. We found that some aligners led to many false positives, whereas others resulted in very few. False negatives were a problem for all aligners, increasing with sequence divergence. Of the aligners tested, PRANK's codon-based alignments consistently performed the best and ClustalW performed the worst. Of the filters tested, GUIDANCE performed the best and Gblocks performed the worst. Although some filters showed good ability to reduce the error rates from ClustalW and MAFFT alignments, none were found to substantially improve the performance of PRANK alignments under most conditions. Our results revealed distinct trends in error rates and power levels for aligners and filters within a biologically plausible parameter space. With the best aligner, a low false positive rate was maintained even with extremely divergent indel-prone sequences. Controls using the true alignment and an optimal filtering method suggested that performance improvements could be gained by improving aligners or filters to reduce the prevalence of false negatives, especially at higher divergence levels and indel rates. PMID- 22049067 TI - Epstein-Barr virus: an important vaccine target for cancer prevention. AB - Participants at the February 2011 meeting at the U.S. National Institutes of Health on Epstein-Barr virus (EBV) vaccine research recommend that future clinical trials have two goals: prevention of infectious mononucleosis and EBV associated cancers, facilitated by identification of disease-predictive surrogate markers. PMID- 22049068 TI - Epigenetics of nicotine: another nail in the coughing. AB - In a mouse model, chronic nicotine exposure before cocaine use exacerbated the epigenetic, gene-expression, electrophysiological, and behavioral effects that occur during the transition from acute to chronic responses to cocaine that have been linked with the addictive process. Nicotine enhancement of the effects can be mimicked with an inhibitor of chromatin-modifying enzymes (class I and II histone deacetylases). These findings may spur the discovery of therapeutics for the treatment of addiction. PMID- 22049069 TI - Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine. AB - In human populations, cigarettes and alcohol generally serve as gateway drugs, which people use first before progressing to marijuana, cocaine, or other illicit substances. To understand the biological basis of the gateway sequence of drug use, we developed an animal model in mice and used it to study the effects of nicotine on subsequent responses to cocaine. We found that pretreatment of mice with nicotine increased the response to cocaine, as assessed by addiction-related behaviors and synaptic plasticity in the striatum, a brain region critical for addiction-related reward. Locomotor sensitization was increased by 98%, conditioned place preference was increased by 78%, and cocaine-induced reduction in long-term potentiation (LTP) was enhanced by 24%. The responses to cocaine were altered only when nicotine was administered first, and nicotine and cocaine were then administered concurrently. Reversing the order of drug administration was ineffective; cocaine had no effect on nicotine-induced behaviors and synaptic plasticity. Nicotine primed the response to cocaine by enhancing its ability to induce transcriptional activation of the FosB gene through inhibition of histone deacetylase, which caused global histone acetylation in the striatum. We tested this conclusion further and found that a histone deacetylase inhibitor simulated the actions of nicotine by priming the response to cocaine and enhancing FosB gene expression and LTP depression in the nucleus accumbens. Conversely, in a genetic mouse model characterized by reduced histone acetylation, the effects of cocaine on LTP were diminished. We achieved a similar effect by infusing a low dose of theophylline, an activator of histone deacetylase, into the nucleus accumbens. These results from mice prompted an analysis of epidemiological data, which indicated that most cocaine users initiate cocaine use after the onset of smoking and while actively still smoking, and that initiating cocaine use after smoking increases the risk of becoming dependent on cocaine, consistent with our data from mice. If our findings in mice apply to humans, a decrease in smoking rates in young people would be expected to lead to a decrease in cocaine addiction. PMID- 22049070 TI - Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity. AB - Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and acute pancreatitis. Although individuals with more body fat and higher serum cytokines and lipase are more likely to experience problems, the roles that these characteristics play are not clear. We used severe acute pancreatitis as a representative disease to investigate the effects of obesity on local organ function and systemic processes. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. In vitro studies of pancreatic acinar cells showed that unsaturated fatty acids were proinflammatory, releasing intracellular calcium, inhibiting mitochondrial complexes I and V, and causing necrosis. Saturated fatty acids had no such effects. Inhibition of lipolysis in obese (ob/ob) mice with induced pancreatitis prevented a rise in serum unsaturated fatty acids and prevented renal injury, lung injury, systemic inflammation, hypocalcemia, reduced pancreatic necrosis, and mortality. Thus, therapeutic approaches that target unsaturated fatty acid mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis. PMID- 22049071 TI - ALDH2 activator inhibits increased myocardial infarction injury by nitroglycerin tolerance. AB - Nitroglycerin, which treats impaired cardiac function through vasodilation as it is converted to nitric oxide, is used worldwide for patients with various ischemic and congestive cardiac diseases, including angina pectoris. Nevertheless, after continuous treatment, the benefits of nitroglycerin are limited by the development of tolerance to the drug. Nitroglycerin tolerance is a result of inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme essential for cardioprotection in animals subjected to myocardial infarction. Here, we tested the hypothesis that the tolerance that develops as a result of sustained nitroglycerin treatment increases cardiac injury by subsequent myocardial infarction. In a rat model of myocardial infarction, 16 hours of prior, sustained nitroglycerin treatment resulted in infarcts that were twice as large as those in untreated control animals and in diminished cardiac function at 3 days and 2 weeks after the myocardial infarction. We also sought to identify a potential treatment to protect against this increased cardiac damage. Nitroglycerin inhibited ALDH2 activity in vitro, an effect that was blocked by Alda-1, an activator of ALDH2. Co-administration of Alda-1 with the nitroglycerin prevented the nitroglycerin-induced increase in cardiac dysfunction after myocardial infarction in rats, at least in part by enhancing metabolism of reactive aldehyde adducts that impair normal protein functions. If our animal studies showing that nitroglycerin tolerance increases cardiac injury upon ischemic insult are corroborated in humans, activators of ALDH2 such as Alda-1 may help to protect patients with myocardial infarction from this nitroglycerin-induced increase in cardiac injury while maintaining the cardiac benefits of the increased nitric oxide concentrations produced by nitroglycerin. PMID- 22049072 TI - Activation of TRPV4 on dural afferents produces headache-related behavior in a preclinical rat model. AB - BACKGROUND: The mechanisms contributing to the pain of migraine are poorly understood although activation of afferent nociceptors in the trigeminovascular system has been proposed as a key event. Prior studies have shown that dural afferent nociceptors are sensitive to both osmotic and mechanical stimuli. Based on the sensitivity to these stimuli we hypothesized that dural afferents express the osmo/mechano-sensitive channel transient receptor-potential vanilloid 4 (TRPV4). METHODS: These studies used in vitro patch-clamp electrophysiology of trigeminal neurons retrogradely labeled from the dura to examine the functional expression of TRPV4. Additionally, we used a rat headache model in which facial/hind paw allodynia following dural stimulation is measured to determine whether activation of meningeal TRPV4 produces responses consistent with migraine. RESULTS: These studies found that 56% and 49% of identified dural afferents generate currents in response to hypotonic solutions and 4alpha-PDD, respectively. The response to these stimuli indicates that dural afferents express TRPV4. Activation of meningeal TPRV4 using hypotonic solution or 4alpha PDD in vivo resulted in both facial and hind paw allodynia that was blocked by the TRPV4 antagonist RN1734. CONCLUSION: These data indicate that activation of TRPV4 within the meninges produces afferent nociceptive signaling from the head that may contribute to migraine headache. PMID- 22049073 TI - Lowered expression of heparan sulfate/heparin biosynthesis enzyme N-deacetylase/n sulfotransferase 1 results in increased sulfation of mast cell heparin. AB - Deficiency of the heparan sulfate biosynthesis enzyme N-deacetylase/N sulfotransferase 1 (NDST1) in mice causes severely disturbed heparan sulfate biosynthesis in all organs, whereas lack of NDST2 only affects heparin biosynthesis in mast cells (MCs). To investigate the individual and combined roles of NDST1 and NDST2 during MC development, in vitro differentiated MCs derived from mouse embryos and embryonic stem cells, respectively, have been studied. Whereas MC development will not occur in the absence of both NDST1 and NDST2, lack of NDST2 alone results in the generation of defective MCs. Surprisingly, the relative amount of heparin produced in NDST1(+/-) and NDST1(-/ ) MCs is higher (~30%) than in control MCs where ~95% of the (35)S-labeled glycosaminoglycans produced is chondroitin sulfate. Lowered expression of NDST1 also results in a higher sulfate content of the heparin synthesized and is accompanied by increased levels of stored MC proteases. A model of the GAGosome, a hypothetical Golgi enzyme complex, is used to explain the results. PMID- 22049074 TI - RB1CC1 protein suppresses type II collagen synthesis in chondrocytes and causes dwarfism. AB - RB1-inducible coiled-coil 1 (RB1CC1) functions in various processes, such as cell growth, differentiation, senescence, apoptosis, and autophagy. The conditional transgenic mice with cartilage-specific RB1CC1 excess that were used in the present study were made for the first time by the Cre-loxP system. Cartilage specific RB1CC1 excess caused dwarfism in mice without causing obvious abnormalities in endochondral ossification and subsequent skeletal development from embryo to adult. In vitro and in vivo analysis revealed that the dwarf phenotype in cartilaginous RB1CC1 excess was induced by reductions in the total amount of cartilage and the number of cartilaginous cells, following suppressions of type II collagen synthesis and Erk1/2 signals. In addition, we have demonstrated that two kinds of SNPs (T-547C and C-468T) in the human RB1CC1 promoter have significant influence on the self-transcriptional level. Accordingly, human genotypic variants of RB1CC1 that either stimulate or inhibit RB1CC1 transcription in vivo may cause body size variations. PMID- 22049075 TI - Loading-related regulation of transcription factor EGR2/Krox-20 in bone cells is ERK1/2 protein-mediated and prostaglandin, Wnt signaling pathway-, and insulin like growth factor-I axis-dependent. AB - Of the 1,328 genes revealed by microarray to be differentially regulated by disuse, or at 8 h following a single short period of osteogenic loading of the mouse tibia, analysis by predicting associated transcription factors from annotated affinities revealed the transcription factor EGR2/Krox-20 as being more closely associated with more pathways and functions than any other. Real time quantitative PCR confirmed up-regulation of Egr2 mRNA expression by loading of the tibia in vivo. In vitro studies where strain was applied to primary cultures of mouse tibia-derived osteoblastic cells and the osteoblast UMR106 cell line also showed up-regulation of Egr2 mRNA expression. In UMR106 cells, inhibition of beta1/beta3 integrin function had no effect on strain-related Egr2 expression, but it was inhibited by a COX2-selective antagonist and imitated by exogenous prostaglandin E2 (PGE2). This response to PGE(2) was mediated chiefly through the EP1 receptor and involved stimulation of PKC and attenuation by cAMP/PKA. Neither activators nor inhibitors of nitric oxide, estrogen signaling, or LiCl had any effect on Egr2 mRNA expression, but it was increased by both insulin-like growth factor-1 and high, but not low, dose parathyroid hormone and exogenous Wnt-3a. The increases by strain, PGE2, Wnt-3a, and phorbol 12-myristate 13-acetate were attenuated by inhibition of MEK-1. EGR2 appears to be involved in many of the signaling pathways that constitute early responses of bone cells to strain. These pathways all have multiple functions. Converting their strain-related responses into coherent "instructions" for adaptive (re)modeling is likely to depend upon their contextual activation, suppression, and interaction probably on more than one occasion. PMID- 22049076 TI - Myocardin-related transcription factor-A complexes activate type I collagen expression in lung fibroblasts. AB - Pulmonary fibrosis is characterized by the excessive deposition of a collagen rich extracellular matrix. The accumulation of collagen within the lung interstitium leads to impaired respiratory function. Furthermore, smooth muscle actin-positive myofibroblasts within the fibrotic lung contribute to disease progression. Because collagen and smooth muscle cell alpha-actin are coordinately expressed in the setting of fibrosis, the hypothesis was tested that specific transcriptional regulators of the myocardin family might also regulate collagen gene expression in myofibroblasts. Myocardin-related transcription factors (MRTFs), through their interaction with the serum-response factor (SRF) on CArG box regulatory elements (CC(A/T)6GG), are important regulators of myofibroblast differentiation. MRTF-A transactivated type I collagen gene reporters as much as 100-fold in lung myofibroblasts. Loss of functional MRTF-A using either a dominant negative MRTF-A isoform, shRNA targeting MRTF-A, or genetic deletion of MRTF-A in lung fibroblasts significantly disrupted type I collagen synthesis relative to controls. Analysis of the COL1A2 proximal promoter revealed a noncanonical CArG box (CCAAACTTGG), flanked by several Sp1 sites important for MRTF-A activation. Chromatin immunoprecipitation experiments confirmed the co localization of MRTF-A, SRF, and Sp1 bound to the same region of the COL1A2 promoter. Mutagenesis of either the noncanonical CArG box or the Sp1 sites significantly disrupted MRTF-A activation of COL1A2. Together, our findings show that MRTF-A is an important regulator of collagen synthesis in lung fibroblasts and exhibits a dependence on both SRF and Sp1 function to enhance collagen expression. PMID- 22049077 TI - Genetic modifiers of cardiovascular phenotype caused by elastin haploinsufficiency act by extrinsic noncomplementation. AB - Elastin haploinsufficiency causes the cardiovascular complications associated with Williams-Beuren syndrome and isolated supravalvular aortic stenosis. Significant variability exists in the vascular pathology in these individuals. Using the Eln(+/-) mouse, we sought to identify the source of this variability. Following outcrossing of C57Bl/6J Eln(+/-), two backgrounds were identified whose cardiovascular parameters deviated significantly from the parental strain. F1 progeny of the C57Bl/6J; Eln(+/-)x129X1/SvJ were more hypertensive and their arteries less compliant. In contrast, Eln(+/-) animals crossed to DBA/2J were protected from the pathologic changes associated with elastin insufficiency. Among the crosses, aortic elastin and collagen content did not correlate with quantitative vasculopathy traits. Quantitative trait locus analysis performed on F2 C57; Eln(+/-)x129 intercrosses identified highly significant peaks on chromosome 1 (LOD 9.7) for systolic blood pressure and on chromosome 9 (LOD 8.7) for aortic diameter. Additional peaks were identified that affect only Eln(+/-), including a region upstream of Eln on chromosome 5 (LOD 4.5). Bioinformatic analysis of the quantitative trait locus peaks revealed several interesting candidates, including Ren1, Ncf1, and Nos1; genes whose functions are unrelated to elastic fiber assembly, but whose effects may synergize with elastin insufficiency to predispose to hypertension and stiffer blood vessels. Real time RT-PCR studies show background-specific increased expression of Ncf1 (a subunit of the NOX2 NAPDH oxidase) that parallel the presence of increased oxidative stress in Eln(+/-) aortas. This finding raises the possibility that polymorphisms in genes affecting the generation of reactive oxygen species alter cardiovascular function in individuals with elastin haploinsufficiency through extrinsic noncomplementation. PMID- 22049078 TI - Nucleolin protein interacts with microprocessor complex to affect biogenesis of microRNAs 15a and 16. AB - MicroRNAs (miRNA) are endogenous, short, non-coding RNA that undergo a multistep biogenesis before generating the functional, mature sequence. The core components of the microprocessor complex, consisting of Drosha and DGCR8, are both necessary and sufficient for this process, although accessory proteins have been found that modulate the biogenesis of a subset of miRNA. Curiously, many of the proteins involved in miRNA biogenesis are also needed for ribosomal RNA processing. Here we show that nucleolin, another protein critical for rRNA processing, is involved in the biogenesis of microRNA 15a/16 (miR-15a/16), specifically at the primary to precursor stage of processing. Through overexpression and knockdown studies, we show that miR-15a/16 levels are directly correlated to nucleolin expression. Furthermore, we found that cellular localization is critical for the proper functioning of nucleolin in this pathway and that nucleolin directly interacts with DGCR8 and Drosha in the nucleus. Nucleolin can bind to the primary miRNA both directly and specifically. Finally, we show that in the absence of nucleolin, cell extracts are unable to process miR-15a/16 in vitro and that this can be rescued by the addition of nucleolin. Our findings offer a new protein component in the microRNA biogenesis pathway and lend insight into miRNA dysregulation in certain cancers. PMID- 22049079 TI - Two distinct sites in sonic Hedgehog combine for heparan sulfate interactions and cell signaling functions. AB - Hedgehog (Hh) proteins are morphogens that mediate many developmental processes. Hh signaling is significant for many aspects of embryonic development, whereas dysregulation of this pathway is associated with several types of cancer. Hh proteins require heparan sulfate proteoglycans (HSPGs) for their normal distribution and signaling activity. Here, we have used molecular modeling to examine the heparin-binding domain of sonic hedgehog (Shh). In biochemical and cell biological assays, the importance of specific residues of the putative heparin-binding domain for signaling was assessed. It was determined that key residues in human (h) Shh involved in heparin and HSPG syndecan-4 binding and biological activity included the well known cationic Cardin-Weintraub motif (lysines 32-38) but also a previously unidentified major role for lysine 178. The activity of Shh mutated in these residues was tested by quantitation of alkaline phosphatase activity in C3H10T1/2 cells differentiating into osteoblasts and hShh inducible gene expression in PANC1 human pancreatic ductal adenocarcinoma cells. Mutated hShhs such as K37S/K38S, K178S, and particularly K37S/K38S/K178S that could not interact with heparin efficiently had reduced signaling activity compared with wild type hShh or a control mutation (K74S). In addition, the mutant hShh proteins supported reduced proliferation and invasion of PANC1 cells compared with control hShh proteins, following endogenous hShh depletion by RNAi knockdown. The data correlated with reduced Shh multimerization where the Lys 37/38 and/or Lys-178 mutations were examined. These studies provide a new insight into the functional roles of hShh interactions with HSPGs, which may allow targeting this aspect of hShh biology in, for example, pancreatic ductal adenocarcinoma. PMID- 22049080 TI - Anion activation site of insulin-degrading enzyme. AB - Insulin-degrading enzyme (IDE) (insulysin) is a zinc metallopeptidase that metabolizes several bioactive peptides, including insulin and the amyloid beta peptide. IDE is an unusual metallopeptidase in that it is allosterically activated by both small peptides and anions, such as ATP. Here, we report that the ATP-binding site is located on a portion of the substrate binding chamber wall arising largely from domain 4 of the four-domain IDE. Two variants having residues in this site mutated, IDEK898A,K899A,S901A and IDER429S, both show greatly decreased activation by the polyphosphate anions ATP and PPPi. IDEK898A,K899A,S901A is also deficient in activation by small peptides, suggesting a possible mechanistic link between the two types of allosteric activation. Sodium chloride at high concentrations can also activate IDE. There are no observable differences in average conformation between the IDE-ATP complex and unliganded IDE, but regions of the active site and C-terminal domain do show increased crystallographic thermal factors in the complex, suggesting an effect on dynamics. Activation by ATP is shown to be independent of the ATP hydrolysis activity reported for the enzyme. We also report that IDEK898A,K899A,S901A has reduced intracellular function relative to unmodified IDE, consistent with a possible role for anion activation of IDE activity in vivo. Together, the data suggest a model in which the binding of anions activates by reducing the electrostatic attraction between the two halves of the enzyme, shifting the partitioning between open and closed conformations of IDE toward the open form. PMID- 22049081 TI - Photosystem I of Chlamydomonas reinhardtii contains nine light-harvesting complexes (Lhca) located on one side of the core. AB - In this work we have purified the Photosystem I (PSI) complex of Chlamydomonas reinhardtii to homogeneity. Biochemical, proteomic, spectroscopic, and structural analyses reveal the main properties of this PSI-LHCI supercomplex. The data show that the largest purified complex is composed of one core complex and nine Lhca antennas and that it contains all Lhca gene products. A projection map at 15 A resolution obtained by electron microscopy reveals that the Lhcas are organized on one side of the core in a double half-ring arrangement, in contrast with previous suggestions. A series of stable disassembled PSI-LHCI intermediates was purified. The analysis of these complexes suggests the sequence of the assembly/disassembly process. It is shown that PSI-LHCI of C. reinhardtii is larger but far less stable than the complex from higher plants. Lhca2 and Lhca9 (the red-most antenna complexes), although present in the largest complex in 1:1 ratio with the core, are only loosely associated with it. This can explain the large variation in antenna composition of PSI-LHCI from C. reinhardtii found in the literature. The analysis of several subcomplexes with reduced antenna size allows determination of the position of Lhca2 and Lhca9 and leads to a proposal for a model of the organization of the Lhcas within the PSI-LHCI supercomplex. PMID- 22049082 TI - FHL2 protein is a novel co-repressor of nuclear receptor Nur77. AB - The three members of the NR4A orphan nuclear receptor subfamily Nur77, Nurr1, and NOR-1, regulate a variety of biological functions including vascular disease and metabolism. In this study, we identified Four and a half LIM domains protein-2 (FHL2) as a novel interacting protein of NR4A nuclear receptors by yeast two hybrid screen and co-immunoprecipitation studies. Each of the four LIM domains of FHL2 can bind Nur77, and both the amino-terminal domain and the DNA binding domain of Nur77 are involved in the interaction between FHL2 and Nur77. FHL2 represses Nur77 transcriptional activity in a dose-dependent manner, and short hairpin RNA-mediated knockdown of FHL2 results in increased Nur77 transcriptional activity. ChIP experiments on the enolase3 promoter revealed that FHL2 inhibits the association of Nur77 with DNA. FHL2 is highly expressed in human endothelial and smooth muscle cells, but not in monocytes or macrophages. To substantiate functional involvement of FHL2 in smooth muscle cell physiology, we demonstrated that FHL2 overexpression increases the growth of these cells, whereas FHL2 knockdown results in reduced DNA synthesis. Collectively, these studies suggest that association of FHL2 with Nur77 plays a pivotal role in vascular disease. PMID- 22049083 TI - Nucleus-localized antisense small RNAs with 5'-polyphosphate termini regulate long term transcriptional gene silencing in Entamoeba histolytica G3 strain. AB - In the deep-branching eukaryotic parasite Entamoeba histolytica, transcriptional gene silencing (TGS) of the Amoebapore A gene (ap-a) in the G3 strain has been reported with subsequent development of this parasite strain for gene silencing. However, the mechanisms underlying this gene silencing approach are poorly understood. Here we report that antisense small RNAs (sRNAs) specific to the silenced ap-a gene can be identified in G3 parasites. Furthermore, when additional genes are silenced in the G3 strain, antisense sRNAs to the newly silenced genes can also be detected. Characterization of these sRNAs demonstrates that they are ~27 nucleotides in size, have 5'-polyphosphate termini, and persist even after removal of the silencing plasmid. Immunofluorescence analysis (IFA) and fluorescence in situ hybridization (FISH) show that both the Argonaute protein EhAGO2-2 and antisense sRNAs to the silenced genes are localized to the parasite nucleus. Furthermore, alpha-EhAGO2-2 immunoprecipitation confirmed the direct association of the antisense sRNAs with EhAGO2-2. Finally, chromatin immunoprecipitation (ChIP) assays demonstrate that the loci of the silenced genes are enriched for histone H3 and EhAGO2-2, indicating that both chromatin modification and the RNA-induced transcriptional silencing complex are involved in permanent gene silencing in G3 parasites. In conclusion, our data demonstrate that G3-based gene silencing in E. histolytica is mediated by an siRNA pathway, which utilizes antisense 5'-polyphosphate sRNAs. To our knowledge, this is the first study to show that 5'- polyphosphate antisense sRNAs can mediate TGS, and it is the first example of RNAi-mediated TGS in protozoan parasites. PMID- 22049084 TI - High temperature requirement factor A1 (HTRA1) gene regulates angiogenesis through transforming growth factor-beta family member growth differentiation factor 6. AB - Genome-wide association study (GWAS) has identified genetic variants in the promoter region of the high temperature requirement factor A1 (HTRA1) gene associated with age-related macular degeneration (AMD). As a secreted serine protease, HTRA1 has been reported to interact with members of the transforming growth factor-beta (TGF-beta) family and regulate their signaling pathways. Growth differentiation factor 6 (GDF6), a member of the TGF-beta family, is involved in ectoderm patterning and eye development. Mutations in GDF6 have been associated with abnormal eye development that may result in microphthalmia and anophthalmia. In this report, we identified a single nucleotide polymorphism (SNP) rs6982567 A/G near the GDF6 gene that is significantly associated with AMD (p value = 3.54 * 10(-8)). We demonstrated that the GDF6 AMD risk allele (rs6982567 A) is associated with decreased expression of the GDF6 and increased expression of HTRA1. Similarly, the HTRA1 AMD risk allele (rs10490924 T) is associated with decreased GDF6 and increased HTRA1 expression. We observed decreased vascular development in the retina and significant up-regulation of GDF6 gene in the RPE layer, retinal and brain tissues in HTRA1 knock-out (htra1( /-)) mice as compared with the wild-type counterparts. Furthermore, we showed enhanced SMAD signaling in htra1(-/-) mice. Our data suggests a critical role of HTRA1 in the regulation of angiogenesis via TGF-beta signaling and identified GDF6 as a novel disease gene for AMD. PMID- 22049085 TI - Probing the origin of the metabolic precursor of the CO ligand in the catalytic center of [NiFe] hydrogenase. AB - The O(2)-tolerant [NiFe] hydrogenases of Ralstonia eutropha are capable of H(2) conversion in the presence of ambient O(2). Oxygen represents not only a challenge for catalysis but also for the complex assembling process of the [NiFe] active site. Apart from nickel and iron, the catalytic center contains unusual diatomic ligands, namely two cyanides (CN(-)) and one carbon monoxide (CO), which are coordinated to the iron. One of the open questions of the maturation process concerns the origin and biosynthesis of the CO group. Isotope labeling in combination with infrared spectroscopy revealed that externally supplied gaseous (13)CO serves as precursor of the carbonyl group of the regulatory [NiFe] hydrogenase in R. eutropha. Corresponding (13)CO titration experiments showed that a concentration 130-fold higher than ambient CO (0.1 ppmv) caused a 50% labeling of the carbonyl ligand in the [NiFe] hydrogenase, leading to the conclusion that the carbonyl ligand originates from an intracellular metabolite. A novel setup allowed us to the study effects of CO depletion on maturation in vivo. Upon induction of CO depletion by addition of the CO scavenger PdCl(2), cells cultivated on H(2), CO(2), and O(2) showed severe growth retardation at low cell concentrations, which was on the basis of partially arrested hydrogenase maturation, leading to reduced hydrogenase activity. This suggests gaseous CO as a metabolic precursor under these conditions. The addition of PdCl(2) to cells cultivated heterotrophically on organic substrates had no effect on hydrogenase maturation. These results indicate at least two different pathways for biosynthesis of the CO ligand of [NiFe] hydrogenase. PMID- 22049086 TI - Some methodological points to consider when performing systematic reviews in comparative effectiveness research. AB - BACKGROUND: The purpose of comparative effectiveness research (CER) is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels. There is an ongoing discussion as to what types of evidence are appropriate to inform CER and how best to interpret various forms of evidence. PURPOSE: The purpose of this article is primarily to highlight several interesting methodological issues in the conduct of CER reviews. METHODS: We describe several key challenges related to randomized trials, with a particular focus on noninferiority studies, which include active comparators used to assess 'assay sensitivity' (defined below), and on the use of randomized studies to perform indirect comparisons between therapies. We touch briefly on the use of observational studies in CER, particularly because of the importance of observational studies in assessing infrequently occurring harms. RESULTS: We argue that studies that may be perceived as unsuitable to address some CER questions may well be appropriate to address others. As an example, noninferiority studies (assuming they include an appropriate comparator at an appropriate dose), are sometimes discounted or excluded from consideration because of concerns that the sponsor's incentive is to conduct a study that is biased toward showing no difference between the treatment groups. If the purpose of a systematic review of CER is to show superiority with respect to a purported benefit, including studies that may be biased toward equality of treatments would tend to underestimate the proposed benefit, that is, the bias works against the sponsor. LIMITATIONS: This is not a comprehensive review of all methodological issues related to CER, and we recognize that there may be dissenting opinions regarding some of the points we raise. CONCLUSIONS: In considering the use of systematic reviews, we believe it is sound advice to perform the head-to-head comparison when possible, in the relevant populations, using endpoints relevant to patients, caregivers, physicians, or payers. These endpoints should include patient-reported outcomes (e.g., symptoms), when relevant. Indirect comparisons and mixed treatment meta analyses may be useful for simultaneously comparing multiple treatments, provided the assumptions underlying such analyses are plausible. PMID- 22049087 TI - A new dependence parameter approach to improve the design of cluster randomized trials with binary outcomes. AB - BACKGROUND AND PURPOSE: Power and sample size calculations for cluster randomized trials require prediction of the degree of correlation that will be realized among outcomes of participants in the same cluster. This correlation is typically quantified as the intraclass correlation coefficient (ICC), defined as the Pearson correlation between two members of the same cluster or proportion of the total variance attributable to variance between clusters. It is widely known but perhaps not fully appreciated that for binary outcomes, the ICC is a function of outcome prevalence. Hence, the ICC and the outcome prevalence are intrinsically related, making the ICC poorly generalizable across study conditions and between studies with different outcome prevalences. METHODS: We use a simple parametrization of the ICC that aims to isolate that part of the ICC that measures dependence among responses within a cluster from the outcome prevalence. We incorporate this parametrization into sample size calculations for cluster randomized trials and compare our method to the traditional approach using the ICC. RESULTS: Our dependence parameter, R, may be less influenced by outcome prevalence and has an intuitive meaning that facilitates interpretation. Estimates of R from previous studies can be obtained using simple statistics. Comparison of methods showed that the traditional ICC approach to sample size determination tends to overpower studies under many scenarios, calling for more clusters than truly required. LIMITATIONS: The methods are developed for equal sized clusters, whereas cluster size may vary in practice. CONCLUSIONS: The dependence parameter R is an alternative measure of dependence among binary outcomes in cluster randomized trials that has a number of advantages over the ICC. PMID- 22049088 TI - Transparency in the presentation of trial results may not increase patients' trust in medical researchers. AB - BACKGROUND: One of the expected benefits of sharing trial results with participants is that it may enhance trust in medical researchers (TMRs). PURPOSE: In a prospective study on a sample of clinical trial participants, we investigated the effect on the participants' TMRs of providing final trial results to participants via the Internet. METHODS: Participants in the FNCLCC PACS04 trial (ClinicalTrials.gov Identifier: NCT00054587) were surveyed on average 6 years after enrollment, when the trial results were available. In the current study, they were randomized to receive (experimental group) or not to receive (control group) a letter informing them that the results of the trial could be consulted on a specific website. TMRs was measured before randomization and 6 months later using mailed self-administered questionnaires. RESULTS: The response rate was 93% (N = 107). TMRs remained unchanged in the control group (mean effect size = -0.06, 95% confidence interval (CI): -0.28 to 0.17, p = 0.617) but decreased in the experimental group (-0.30, 95% CI: -0.53 to -0.06, p = 0.015). However, the difference between the two effect sizes was not statistically significant (p = 0.144). LIMITATIONS: The results obtained here on the disclosure of final trial results to breast cancer patients via the Internet cannot be generalized to all situations involving the disclosure of phase III randomized controlled trial results. CONCLUSIONS: Transparency is an ethical research requirement, but it may not enhance participants' TMRs. PMID- 22049089 TI - Choristoneura fumiferana multiple nucleopolyhedrovirus LEF-3-P143 complex can complement DNA replication and budded virus in an AcMNPV LEF-3-P143 double knockout bacmid. AB - Transient replication assays using Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Choristoneura fumiferana multiple nucleopolyhedrovirus (CfMNPV) genes suggested that the interactions between P143, the viral helicase and LEF-3, a ssDNA-binding protein, may represent virus species specificity determinants. P143 and LEF-3 are essential for DNA replication in these assays and together with IE-1, the major immediate-early transcription factor, may be part of the viral replisome. In the current report, a lef-3/p143 double-knockout AcMNPV bacmid was constructed that was defective for viral DNA replication and late gene expression. When the homologous lef-3/p143 CfMNPV genes were introduced into this double-knockout bacmid, DNA replication was restored but the level of replication was lower, budded virus production was delayed, and the yields were reduced from those in an AcMNPV-rescue bacmid. These results suggest that to maximize virus replication, baculovirus replisome assembly and function requires protein-protein interactions between P143 and LEF 3, and other viral proteins. PMID- 22049090 TI - Raspberry leaf blotch virus, a putative new member of the genus Emaravirus, encodes a novel genomic RNA. AB - A new, segmented, negative-strand RNA virus with morphological and sequence similarities to other viruses in the genus Emaravirus was discovered in raspberry plants exhibiting symptoms of leaf blotch disorder, a disease previously attributed to the eriophyid raspberry leaf and bud mite (Phyllocoptes gracilis). The virus, tentatively named raspberry leaf blotch virus (RLBV), has five RNAs that each potentially encode a single protein on the complementary strand. RNAs 1, 2 and 3 encode, respectively, a putative RNA-dependent RNA polymerase, a glycoprotein precursor and the nucleocapsid. RNA4 encodes a protein with sequence similarity to proteins of unknown function that are encoded by the genomes of other emaraviruses. When expressed transiently in plants fused to green or red fluorescent protein, the RLBV P4 protein localized to the peripheral cell membrane and to punctate spots in the cell wall. These spots co-localized with GFP-tagged tobacco mosaic virus 30K cell-to-cell movement protein, which is itself known to associate with plasmodesmata. These results suggest that the P4 protein may be a movement protein for RLBV. The fifth RLBV RNA, encoding the P5 protein, is unique among the sequenced emaraviruses. The amino acid sequence of the P5 protein does not suggest any potential function; however, when expressed as a GFP fusion, it localized as small aggregates in the cytoplasm near to the periphery of the cell. PMID- 22049091 TI - The role of neutralizing antibodies in hepatitis C virus infection. AB - Hepatitis C virus (HCV) is a blood-borne virus estimated to infect around 170 million people worldwide and is, therefore, a major disease burden. In some individuals the virus is spontaneously cleared during the acute phase of infection, whilst in others a persistent infection ensues. Of those persistently infected, severe liver diseases such as cirrhosis and primary liver cancer may develop, although many individuals remain asymptomatic. A range of factors shape the course of HCV infection, not least host genetic polymorphisms and host immunity. A number of studies have shown that neutralizing antibodies (nAb) arise during HCV infection, but that these antibodies differ in their breadth and mechanism of neutralization. Recent studies, using both mAbs and polyclonal sera, have provided an insight into neutralizing determinants and the likely protective role of antibodies during infection. This understanding has helped to shape our knowledge of the overall structure of the HCV envelope glycoproteins--the natural target for nAb. Most nAb identified to date target receptor-binding sites within the envelope glycoprotein E2. However, there is some evidence that other viral epitopes may be targets for antibody neutralization, suggesting the need to broaden the search for neutralization epitopes beyond E2. This review provides a comprehensive overview of our current understanding of the role played by nAb in HCV infection and disease outcome and explores the limitations in the study systems currently used. In addition, we briefly discuss the potential therapeutic benefits of nAb and efforts to develop nAb-based therapies. PMID- 22049092 TI - Co-divergence and host-switching in the evolution of tobamoviruses. AB - The proposed phylogenetic structure of the genus Tobamovirus supports the idea that these viruses have codiverged with their hosts since radiation of the hosts from a common ancestor. The determinations of genome sequence for two strains of Passion fruit mosaic virus (PafMV), a tobamovirus from plants of the family Passifloraceae (order Malpighiales) from which only one other tobamovirus (Maracuja mosaic virus; MarMV) has been characterized, combined with the development of Bayesian analysis methods for phylogenetic inference, provided an opportunity to reassess the co-divergence hypothesis. The sequence of one PafMV strain, PfaMV-TGP, was discovered during a survey of plants of the Tallgrass Prairie Preserve for their virus content. Its nucleotides are only 73 % identical to those of MarMV. A conserved ORF not found in other tobamovirus genomes, and encoding a cysteine-rich protein, was found in MarMV and both PafMV strains. Phylogenetic tree construction, using an alignment of the nucleotide sequences of PafMV-TGP and other tobamoviruses resulted in a major clade containing isolates exclusively from rosid plants. Asterid-derived viruses were exclusively found in a second major clade that also contained an orchid-derived tobamovirus and tobamoviruses infecting plants of the order Brassicales. With a few exceptions, calibrating the virus tree with dates of host divergence at two points resulted in predictions of divergence times of family specific tobamovirus clades that were consistent with the times of divergence of the host plant orders. PMID- 22049093 TI - Immunogenic compositions assembled from tobacco mosaic virus-generated spherical particle platforms and foreign antigens. AB - We reported recently that RNA-free spherical particles (SPs) generated by thermal remodelling of tobacco mosaic virus (TMV) are capable of binding GFP to their surface. Here, we show that SPs represent a universal particle platform that can form compositions by binding a diversity of various foreign proteins/epitopes of viral and non-viral origin to their surface. Numerous molecules of a foreign protein linked to the SP surface were revealed by immunogold electron microscopy. Several SP-based compositions were obtained containing one of the following foreign antigens: antigenic determinant A of rubella virus E1 glycoprotein; a recombinant protein containing the M2e epitope of influenza virus A protein M2; a recombinant antigen consisting of three epitopes of influenza virus A haemagglutinin; potato virus X (PVX) coat protein (CP); BSA; and PVX CP fused with the epitope of plum pox virus CP. The 'mixed' compositions could be also assembled by binding two different foreign antigens to each of the SPs. Immunogenicity of foreign antigens adsorbed or linked covalently to SPs in the SP based compositions was examined. The antigenic specificity of foreign antigens was retained, whereas their immunogenicity increased significantly. It was inferred that SPs exhibit immunopotentiating activity, in particular in the form of compositions comprising SP and foreign antigen linked covalently to their surface by formaldehyde. PMID- 22049094 TI - Activation of the beta interferon promoter by paramyxoviruses in the absence of virus protein synthesis. AB - Conflicting reports exist regarding the requirement for virus replication in interferon (IFN) induction by paramyxoviruses. Our previous work has demonstrated that pathogen-associated molecular patterns capable of activating the IFN induction cascade are not normally generated during virus replication, but are associated instead with the presence of defective interfering (DI) viruses. We demonstrate here that DIs of paramyxoviruses, including parainfluenza virus 5, mumps virus and Sendai virus, can activate the IFN-induction cascade and the IFN beta promoter in the absence of virus protein synthesis. As virus protein synthesis is an absolute requirement for paramyxovirus genome replication, our results indicate that these DI viruses do not require replication to activate the IFN-induction cascade. PMID- 22049095 TI - Characterizing the complexity of spontaneous motor unit patterns of amyotrophic lateral sclerosis using approximate entropy. AB - This paper presents a novel application of the approximate entropy (ApEn) measurement for characterizing spontaneous motor unit activity of amyotrophic lateral sclerosis (ALS) patients. High-density surface electromyography (EMG) was used to record spontaneous motor unit activity bilaterally from the thenar muscles of nine ALS subjects. Three distinct patterns of spontaneous motor unit activity (sporadic spikes, tonic spikes and high-frequency repetitive spikes) were observed. For each pattern, complexity was characterized by calculating the ApEn values of the representative signal segments. A sliding window over each segment was also introduced to quantify the dynamic changes in complexity for the different spontaneous motor unit patterns. We found that the ApEn values for the sporadic spikes were the highest, while those of the high-frequency repetitive spikes were the lowest. There is a significant difference in mean ApEn values between two arbitrary groups of the three spontaneous motor unit patterns (P < 0.001). The dynamic ApEn curve from the sliding window analysis is capable of tracking variations in EMG activity, thus providing a vivid, distinctive description for different patterns of spontaneous motor unit action potentials in terms of their complexity. These findings expand the existing knowledge of spontaneous motor unit activity in ALS beyond what was previously obtained using conventional linear methods such as firing rate or inter-spike interval statistics. PMID- 22049096 TI - Effects of pioglitazone and metformin on vascular endothelial function in patients with type 2 diabetes treated with sulfonylureas. AB - Pioglitazone and metformin are insulin sensitisers used for the treatment of T2DM. The effects of pioglitazone and metformin on endothelial function, assessed by FMD, in T2DM patients treated with sulfonylureas were compared. Patients were randomised to receive pioglitazone (n = 15) 30 mg once daily or metformin (n = 16) 850 mg twice daily for six months. Pioglitazone significantly decreased fasting insulin, HbA(1C) and HOMA-IR (p < 0.05 for all) and increased FMD (p = 0.002). Metformin induced a significant decrease in HbA(1C) (p = 0.02) and only a trend for increase in FMD (p = 0.08). The greater improvement in FMD with pioglitazone, compared with metformin, did not reach significance (p = 0.11). Treatment-induced changes in FMD were not associated with the effects of the two insulin sensitisers on glycaemic control or insulin resistance. The beneficial effects of pioglitazone and metformin on endothelial function in T2DM patients did not differ greatly. Larger studies are needed to explore whether a potentially greater benefit with pioglitazone may exist. PMID- 22049098 TI - Finding the atomic configuration with a required physical property in multi-atom structures. AB - In many problems in molecular and solid state structures one seeks to determine the energy-minimizing decoration of sites with different atom types. In other problems, one is interested in finding a decoration with a target physical property (e.g. alloy band gap) within a certain range. In both cases, the sheer size of the configurational space can be horrendous. We present two approaches which identify either the minimum-energy configuration or configurations with a target property for a fixed underlying Bravais lattice. We compare their efficiency at locating the deepest minimum energy configuration of face centered cubic Au-Pd alloy. We show that a global-search genetic-algorithm approach with diversity-enhancing constraints and reciprocal-space mating can efficiently find the global optimum, whereas the local-search virtual-atom approach presented here is more efficient at finding structures with a target property. PMID- 22049097 TI - Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies. AB - The hypothesis is that the mechanical mismatch between brain tissue and microelectrodes influences the inflammatory response. Our unique, mechanically adaptive polymer nanocomposite enabled this study within the cerebral cortex of rats. The initial tensile storage modulus of 5 GPa decreases to 12 MPa within 15 min under physiological conditions. The response to the nanocomposite was compared to surface-matched, stiffer implants of traditional wires (411 GPa) coated with the identical polymer substrate and implanted on the contralateral side. Both implants were tethered. Fluorescent immunohistochemistry labeling examined neurons, intermediate filaments, macrophages, microglia and proteoglycans. We demonstrate, for the first time, a system that decouples the mechanical and surface chemistry components of the neural response. The neuronal nuclei density within 100 um of the device at four weeks post-implantation was greater for the compliant nanocomposite compared to the stiff wire. At eight weeks post-implantation, the neuronal nuclei density around the nanocomposite was maintained, but the density around the wire recovered to match that of the nanocomposite. The glial scar response to the compliant nanocomposite was less vigorous than it was to the stiffer wire. The results suggest that mechanically associated factors such as proteoglycans and intermediate filaments are important modulators of the response of the compliant nanocomposite. PMID- 22049099 TI - Polarization fields of III-nitrides grown in different crystal orientations. AB - This article reviews the piezoelectric properties of III-nitrides with emphasis on GaN, InN, and their ternary alloys. After a short literature survey we concentrate on semipolar and nonpolar quantum wells grown on crystal planes other than the commonly used c plane ({0001}). The electrostatic field within a quantum well causes a quantum confined Stark effect and thus lowers the radiative transition probability as well as the transition energy. The basic impact of the quantum confined Stark effect on the optical properties of GaInN/GaN quantum wells is discussed in detail. Some routes to determine the magnitude of the electric field are described, and recent results are considered. The measured values are compared to published piezoelectric tensor elements. PMID- 22049100 TI - Theory of spontaneous emission of quantum dots in the linear regime. AB - We develop a fully quantum-mechanical theory for the interaction of light and electron-hole excitations in semiconductor quantum dots. Our theoretical analysis results in an expression for the photoluminescence intensity of quantum dots in the linear regime. Taking into account the single-particle Hamiltonian, the free photon Hamiltonian, the electron-hole interaction Hamiltonian, and the interaction of carriers with light, and applying the Heisenberg equation of motion to the photon number expectation values, to the carrier distribution functions and to the correlation term between the photon generation (destruction) and electron-hole pair, we obtain a set of luminescence equations. Under quasi equilibrium conditions, these equations become a closed-set of equations. We solve them analytically, in the linear regime, and we find an approximate solution of the incoherent photoluminescence intensity. The validity of the theoretical analysis is tested by investigating the emission spectra in the high temperature regime, interpreting the experimental findings for the emission spectra of a lens-shaped In(0.5)Ga(0.5)As self-assembled quantum dot. Our theoretical predictions for the interlevel spacing as well as for the dephasing time caused by electron-longitudinal optical phonon interactions are in good agreement with the experimental results. PMID- 22049101 TI - Study of thermal spin crossover in [Fe(II)(isoxazole)(6)](BF(4))(2) with Mossbauer spectroscopy. AB - (57)Fe Mossbauer spectroscopy of the mononuclear [Fe(II)(isoxazole)(6)](BF(4))(2) compound has been studied to reveal the thermal spin crossover of Fe(II) between low-spin (S = 0) and high-spin (S = 2) states. A temperature-dependent spin transition curve has been constructed with the least-square fitted data obtained from the Mossbauer spectra measured at various temperatures in the 240-60 K range during the cooling and heating cycle. The compound exhibits a temperature dependent two-step spin transition phenomenon with T(SCO) (step 1) = 92 and T(SCO) (step 2) = 191 K. The compound has three high-spin Fe(II) sites at the highest temperature of study; among them, two have slightly different coordination environments. These two Fe(II) sites are found to undergo a spin transition, while the third Fe(II) site retains the high-spin state over the whole temperature range. Possible reasons for the formation of the two steps in the spin transition curve are discussed. The observations made from the present study are in complete agreement with those envisaged from earlier magnetic and structural studies made on [Fe(II)(isoxazole)(6)](BF(4))(2), but highlights the nature of the spin crossover mechanism. PMID- 22049102 TI - Dimensional crossover in anisotropic Kondo lattices. AB - Dimensional crossover in the Kondo necklace model is analyzed using the bond operator method at zero and finite temperatures. Explicit relations describing quasi-two-dimensional properties are obtained by asymptotically solving the resulting equations. The crossover from two dimensions (2d) to three dimensions (3d) is investigated, turning on the electronic hopping ([Formula: see text]) of conduction electrons between different planes. In order to give continuity to our analysis, both cases of crossover, quasi-three-dimensional (q3d) and quasi-one dimensional (q1d), are also investigated. The phase diagram as a function of temperature T, [Formula: see text] and [Formula: see text], where [Formula: see text] is the hopping within the planes, is calculated. Unusual reentrant behavior in the temperature-dependent antiferromagnetic critical line is found close to two dimensions. Near the isotropic three-dimensional quantum critical point the critical line is described by a standard power law with a square root dependence on the distance to the quantum critical point. PMID- 22049103 TI - One-dimensional Bi(2)O(3) nanohooks: synthesis, characterization and optical properties. AB - We report the synthesis of one-dimensional (1D) Bi(2)O(3) nanohooks by the oxidative metal vapor phase deposition technique. Surface morphology observations confirm the formation of 1D nanohooks with nanoparticles at their tips. Structural analysis by x-ray diffraction (XRD) and transmission electron microscopy (TEM) reveals the crystalline nature of the 1D nanostructure. Elemental analysis confirms that the 1D nanohooks consist of only elements Bi and O. The XRD study suggests that the synthesized product is of two phases (alpha- and beta-Bi(2)O(3)) with monoclinic and tetragonal crystal structures respectively. The phonon vibration modes corresponding to Bi(2)O(3) are determined by Raman scattering. A broadband visible photoluminescence (PL) is observed in the wavelength region 500-900 nm, also indicating the extension of luminescence into the near-infrared region. The existence of broadband visible emission can be attributed to the existence of defect/impurity states induced by oxygen vacancies. PMID- 22049104 TI - Temperature dependence of the current-voltage characteristics of Sn/PANI/p-Si/Al heterojunctions. AB - Sn/PANI/p-Si/Al heterojunctions were fabricated by electropolymerization of aniline on chemically cleaned p-Si substrates. Current-voltage characteristics of Sn/PANI/p-Si/Al heterojunctions measured in the temperature range 140-280 K are presented and analyzed. Although these devices were clearly rectifying, their I-V characteristics were non-ideal, which can be judged from the nonlinearity in the semi-logarithmic plots. The high values of the ideality factor n depending on the sample temperature may be ascribed to a decrease of the exponentially increasing rate in current due to space-charge injection into the PANI thin film at higher forward bias voltages. Careful analysis of the forward bias I-V characteristics on a log-log scale indicates that the space-charge-limited current (SCLC) conduction controlled by an exponential trap distribution above the valence band edge dominates the current transport in the PANI/p-Si diodes at high voltages. Furthermore, the PANI was characterized by using Fourier transform infrared (FTIR) and ultraviolet-visible (UV-vis) spectra. PMID- 22049105 TI - Cluster expansions in multicomponent systems: precise expansions from noisy databases. AB - We have performed a systematic analysis of the numerical errors contained in the databases used in cluster expansions of multicomponent alloys. Our results underscore the importance of numerical noise in the determination of the effective cluster interactions and in the expansion determination. The relevance of the size of and information contained in the input database is highlighted. It is shown that cross-validatory approaches by themselves can produce unphysical expansions characterized by non-negligible, long-ranged coefficients. A selection criterion that combines both forecasting ability and a physical limiting behavior for the expansion is proposed. Expansions performed under this criterion exhibit the remarkable property of noise filtering. A discussion of the impact of this unforeseen characteristic of the cluster expansion method on the modeling of multicomponent alloy systems is presented. PMID- 22049106 TI - Anomalous structural and magnetic behaviour of Fe-25 at.% Ni alloy due to mechanical strain. AB - Mechanical strain was induced in Fe-25 at.% Ni alloy by filing the ingots into powder form. The phase transformations induced by the deformation thus caused and subsequent annealing were studied by x-ray diffraction, magnetization measurement and Mossbauer spectroscopy. It is concluded that around one-third of the Fe atoms became segregated from the Fe-Ni alloy due to filing. Annealing of the filed powder led to recombination of this segregated Fe to form an apparently body centred cubic (bcc) phase of Fe-Ni which shows little magnetic ordering at room temperature in magnetization measurements or in Mossbauer spectroscopy. The single-line Mossbauer spectrum of this phase splits into a six-line pattern below 100 K. PMID- 22049107 TI - Hyper-parallel tempering Monte Carlo simulations of Ar adsorption in new models of microporous non-graphitizing activated carbon: effect of microporosity. AB - The adsorption of gases on microporous carbons is still poorly understood, partly because the structure of these carbons is not well known. Here, a model of microporous carbons based on fullerene-like fragments is used as the basis for a theoretical study of Ar adsorption on carbon. First, a simulation box was constructed, containing a plausible arrangement of carbon fragments. Next, using a new Monte Carlo simulation algorithm, two types of carbon fragments were gradually placed into the initial structure to increase its microporosity. Thirty six different microporous carbon structures were generated in this way. Using the method proposed recently by Bhattacharya and Gubbins (BG), the micropore size distributions of the obtained carbon models and the average micropore diameters were calculated. For ten chosen structures, Ar adsorption isotherms (87 K) were simulated via the hyper-parallel tempering Monte Carlo simulation method. The isotherms obtained in this way were described by widely applied methods of microporous carbon characterisation, i.e. Nguyen and Do, Horvath-Kawazoe, high resolution alpha(s) plots, adsorption potential distributions and the Dubinin Astakhov (DA) equation. From simulated isotherms described by the DA equation, the average micropore diameters were calculated using empirical relationships proposed by different authors and they were compared with those from the BG method. PMID- 22049108 TI - Continuum modelling for carbon and boron nitride nanostructures. AB - Continuum based models are presented here for certain boron nitride and carbon nanostructures. In particular, certain fullerene interactions, C(60)-C(60), B(36)N(36)-B(36)N(36) and C(60)-B(36)N(36), and fullerene-nanotube oscillator interactions, C(60)-boron nitride nanotube, C(60)-carbon nanotube, B(36)N(36) boron nitride nanotube and B(36)N(36)-carbon nanotube, are studied using the Lennard-Jones potential and the continuum approach, which assumes a uniform distribution of atoms on the surface of each molecule. Issues regarding the encapsulation of a fullerene into a nanotube are also addressed, including acceptance and suction energies of the fullerenes, preferred position of the fullerenes inside the nanotube and the gigahertz frequency oscillation of the inner molecule inside the outer nanotube. Our primary purpose here is to extend a number of established results for carbon to the boron nitride nanostructures. PMID- 22049109 TI - Inhomogeneous electronic states in organic metal (BEDO-TTF)(2)ReO(4).H(2)O: EPR and SQUID study. AB - It is shown by electron paramagnetic resonance (EPR) and superconducting quantum interference device (SQUID) magnetometry that two spin systems coexist in conducting layers of the quasi-2D organic metal (BEDO-TTF)(2)ReO(4).H(2)O: delocalized moments of charge carriers (holes), I(epr)(300 K) = 1.62 * 10(-4) emu mol(-1), and localized moments on BEDO-TTF(+1), chi(p)(300 K) = 4.25 * 10(-4) emu mol(-1). The phase transition Me-Me' at T(c) = 203 K is detected in paramagnetic relaxation, EPR amplitude and resistivity. Magnetic susceptibilities, I(epr) and chi(p), are not sensitive to the transition. Due to fine rearrangement of ReO(4) linked by H(2)O, the electronic spectrum becomes inhomogeneous. Below the transition exchange-coupled localized states within the metallic phase are observed. On cooling, the concentration of delocalized moments gradually decreases, contributing to a localized spin system. The phenomenon is interpreted in terms of short-range antiferromagnetic (AFM) interactions via conducting electrons. Below 14 K the AFM coupled states decay, and paramagnetism of local moments is recovered. PMID- 22049110 TI - First principle calculations of alkali hydride electronic structures. AB - Electronic structure, volume optimization, bulk moduli, elastic constants, and frequencies of the transversal optical vibrations in LiH, NaH, KH, RbH, and CsH are calculated using the full potential augmented plane wave method, extended with local orbitals, and the full potential linearized augmented plane wave method. The obtained results show some common features in the electronic structure of these compounds, but also clear differences, which cannot be explained using simple empirical trends. The differences are particularly prominent in the electronic distributions and interactions in various crystallographic planes. In the light of these findings we have elaborated some selected experimental results and discussed several theoretical approaches frequently used for the description of various alkali hydride properties. PMID- 22049111 TI - Magnetic and electronic properties of Bi(0.75)Ca(0.25)MnO(3). AB - The magnetic, structural and electronic properties of Bi(0.75)Ca(0.25)MnO(3) have been investigated in comparison with those of Bi(0.75)Sr(0.25)MnO(3). Magnetometry, diffraction and muon spin relaxation (MUSR) data confirm different structural, magnetic and electronic transitions in the two compounds. The anisotropic changes of cell parameters across the structural transition in Bi(0.75)Ca(0.25)MnO(3) (275 K) differ markedly from the lattice anomalies in Bi(0.75)Sr(0.25)MnO(3) (600 K) and also from those in Bi(0.50)Ca(0.50)MnO(3) (325 K). The ground state of Bi(0.75)Ca(0.25)MnO(3) is characterized by a high degree of spin disorder and frustrated interactions. There is no evidence of a ferromagnetic component in the ground state of Bi(0.75)Ca(0.25)MnO(3). However, the application of a magnetic field (even of a few gauss) produces a continuous progressive polarization of the Mn moments (~2 MU(B)/Mn at 5 T, ZFC, 5 K). Differences between Ca and Sr perovskites with x = 1/4 are greater than for the x = 1/2 counterparts, and point to distinct ground states and charge/orbital configurations. PMID- 22049112 TI - Prediction for new magnetoelectric fluorides. AB - We use symmetry considerations in order to predict new magnetoelectric fluorides. In addition to these magnetoelectric properties, we discuss which among these fluorides are the ones susceptible to present multiferroic properties. We emphasize that several materials exhibit ferromagnetic properties. This ferromagnetism should enhance the interplay between the magnetic and dielectric properties in these materials. PMID- 22049113 TI - Ionic diffusion within the alpha(*) and beta phases of Ag(3)SI. AB - The ionic diffusion mechanism of mobile ions within an underlying body-centred cubic (bcc) sublattice of immobile counterions is discussed. In particular, the case of equal numbers of two ionic species forming long-range ordered and disordered bcc arrays is considered, since these form the basis of the cubic perovskite and alpha-AgI-type crystal structures, respectively. Their structural behaviour, and its influence on the dynamic ionic disorder which characterizes superionic conduction, is illustrated for the case of Ag(+) diffusion within the beta and alpha(*) phases of Ag(3)SI. The calculated behaviour obtained by molecular dynamics (MD) computer simulations is validated with reference to published neutron diffraction and ionic conductivity measurements of Ag(3)SI, and used to examine the preferred diffusion pathways. The relevance of these findings for the anion conduction mechanisms within perovskite structured compounds is briefly discussed. PMID- 22049114 TI - Effect of particle shape on the density and microstructure of random packings. AB - We study the random packing of non-spherical particles by computer simulation to investigate the effect of particle shape and aspect ratio on packing density and microstructure. Packings of cut spheres (a spherical segment which is symmetric about the centre of the sphere) are simulated to assess the influence of a planar face on packing properties. It turns out that cut spheres, in common with spherocylinders and spheroids, pack more efficiently as the particle's aspect ratio is perturbed slightly from unity (the aspect ratio of a sphere) to reach a maximum density at an aspect ratio of approximately 1.25. Upon increasing the aspect ratio further the cut spheres pack less efficiently, until approximately an aspect ratio of 2, where the particles are found to form a columnar phase. The amount of ordering is sensitive to simulation parameters and for very thin disks the formation of long columns becomes frustrated, resulting in a nematic phase, in marked contrast to the behavior of long thin rods which always randomly pack into entangled isotropic networks. With respect to coordination numbers it appears that cut spheres always pack with significantly fewer contacts than required for isostatic packing. PMID- 22049115 TI - Quasi-transverse ultrasound absorption due to point defects and anharmonic scattering processes in cubic crystals with positive and negative anisotropies of the second-order elastic moduli. AB - The quasi-transverse ultrasound absorption in cubic crystals with positive and negative anisotropies of the second-order elastic moduli is analyzed. The scattering of the ultrasound by point defects and during anharmonic scattering processes is considered. The quasi-transverse ultrasound absorption is analyzed as a function of the wavevector direction in terms of the anisotropic continuum model. The Landau-Rumer mechanism is considered for anharmonic scattering processes. Known values of the second- and third-order elastic moduli are used to calculate parameters determining the ultrasound absorption. It is shown that the angular dependences of the quasi-transverse ultrasound absorption differ qualitatively if the anharmonic scattering processes dominate in cubic crystals with positive and negative anisotropies of the second-order elastic moduli. For the scattering by point defects and the anharmonic scattering processes, the angular dependences of the quasi-transverse ultrasound absorption exhibit the inverse behavior, making it possible to determine the dominating mechanism of the ultrasound relaxation in the crystals under study. PMID- 22049116 TI - Electronic structure and magnetism of EuTiO(3): a first-principles study. AB - Density-functional theory calculations were carried out for the multiferroic EuTiO(3) using the LDA+U approach. Total-energy calculations for ferromagnetic (F), and antiferromagnetic A-, C-, and G-type arrangements in the cubic phase shows that the ground-state magnetic configuration is G-type antiferromagnetic for U<=6 eV and ferromagnetic for U>=7 eV. Values of first- and second-neighbour exchange integrals have been calculated by mapping the energy difference between the different magnetic configurations to a Heisenberg Hamiltonian. The system seems to be critically balanced between ferromagnetic and antiferromagnetic states for realistic values of U, and switches from antiferromagnetic to a ferromagnetic ground state on hydrostatic expansion of volume. PMID- 22049117 TI - Rigid-unit modes in tetrahedral crystals. AB - The 'rigid-unit mode' (RUM) model requires unit blocks, in our case tetrahedra of SiO(4) groups, to be rigid within first order of the displacements of the oxygen ions. The wavevectors of the lattice vibrations, which obey this rigidity, are determined analytically. Lattices with inversion symmetry yield generically surfaces of RUMs in reciprocal space, whereas lattices without this symmetry yield generically lines of RUMs. Only in exceptional cases such as in beta-quartz does a surface of RUMs appear, if inversion symmetry is lacking. The occurrence of planes and bending surfaces, and straight and bent lines, is discussed. Explicit calculations are performed for five polymorphs of SiO(2) crystals. PMID- 22049118 TI - Theoretical study on superconductivity in CeMIn(5) (M = Co, Rh, Ir): pairing symmetry and pressure dependence. AB - We study theoretically heavy fermion superconductors CeMIn(5) (M = Co, Rh, Ir). CeCoIn(5) and CeIrIn(5) that become superconducting at ambient pressure with T(c) = 2.3 K and 0.4 K, respectively. On the other hand, CeRhIn(5) is an antiferromagnet at ambient pressure and becomes superconducting under pressures greater than 1.6 GPa. With regards to the superconductivity, the existence of line nodes is indicated by nuclear-quadrupole-resonance (NQR), thermal conductivity, specific heat and electrical resistivity measurements. However, the pairing symmetry between d(x(2)-y(2)) and d(xy) is controversial. Therefore, we investigate the gap structure of CeMIn(5) by a detailed calculation. We introduce a three-dimensional periodic Anderson model (3D-PAM) in order to reproduce the band characteristics of CeMIn(5). Thus, we identify the gap structure of CeMIn(5) as the d(x(2)-y(2)) symmetry by solving the Eliashberg equations. In addition, we discuss the pressure dependence of T(c) and show that two factors determine T(c). One factor is the momentum dependence of quasi particle interaction and the other factor is the wavefunction renormalization factor. Thus, we have explained the superconductivity in CeMIn(5) using the Fermi liquid theory. PMID- 22049119 TI - Coherent A(1) phonons in Te studied with tailored femtosecond pulses. AB - We tailor the shape and phase of the pump-pulse spectrum in order to study coherent lattice dynamics in tellurium. Employing coherent control by splitting the pump pulse into a two-pulse sequence, we show that the oscillations due to A(1) coherent phonons can be cancelled but not enhanced as compared to single pulse excitation of the same energy. We further demonstrate that a crucial factor for coherent phonon generation seems to be the bandwidth of the pulse spectrum. We observe that the coherent amplitude for long pump pulses decreases exponentially with pulse duration for both Gaussian and rectangular pulses. Finally, by varying the pulse chirp, we show that the coherent amplitude is independent of the chirp sign while the oscillation lifetime is slightly dependent on the chirp sign. PMID- 22049120 TI - Raman analysis of CdSe/CdS core-shell quantum dots with different CdS shell thickness. AB - We report the first-order and high-order Raman scattering from core-shell CdSe/CdS nanocrystals and investigate the evolution of the longitudinal mode of CdSe (LO1) and CdS (LO2), and the surface mode of CdSe (SO1) and CdS (SO2) with increasing shell thickness (0-5.5 ML (monolayer)). We find that the shift of the LO2 peak from 268 to 291 cm(-1) agrees well with the theoretical values based on the phonon confinement model. The variation of the dielectric environment of the CdSe core with increasing CdS shell thickness is modified according to the shift of SO1 from 198 to 185 cm(-1). The SO2 modes at 267 and 275 cm(-1), corresponding to the shell thickness 3.5 and 5.5 ML in CdSe/CdS nanocrystals, respectively, are also obtained for the first time in our experiment. Moreover, they agree well with the theoretical values of the dielectric corresponding function model. Besides, a new Raman peak at 482 cm(-1) is observed, and it remains at that value with shell growth, the new peak is supposed to be caused by the alloying at the core-shell interface. Therefore, Raman spectroscopy can be used to determine the shell thickness and other surface and interface parameters of CdSe/CdS core shell nanocrystals. PMID- 22049121 TI - Scaling behavior of the energy gap of the XXZ model in a transverse magnetic field. AB - The energy gap of the one-dimensional (1D) spin-[Formula: see text] AF (antiferromagnetic) XXZ model in a transverse magnetic field (h) is studied by using the exact diagonalization technique. We have computed the energy gap in the region of anisotropy parameter -17 d as inpatients under management of diabetes with medical nutrition therapy and medications. Insulin secretion was measured with a glucagon test. Stepwise regression was applied to explore determinants of BEE. RESULTS: In the stepwise estimation, insulin secretion (P = 0.015), insulin therapy (P = 0.012), and pulse rate (P = 0.011) were selected in addition to fat-free mass (FFM) (P < 0.001) and fat mass (P = 0.006) as significant independent determinants of BEE. Standardized partial regression coefficients of the additional 3 factors were -0.16, -0.15, and 0.15, respectively, whereas those for FFM and fat mass were 0.82 and 0.19, respectively. The additional 3 factors explained another 3.9% of the variability of BEE, and the adjusted coefficient of determination was 83.4%. Age, sex, other medications, and parameters of glycemic control were not significant determinants beyond the combined contribution of body composition, endogenous and exogenous insulin, and pulse rate. CONCLUSION: Endogenous insulin secretion and exogenous insulin administered in treatment have significant independent effects in the lowering of BEE in patients with diabetes under standard management with medical nutrition therapy and medications. PMID- 22049164 TI - Developmental programming and epigenetics. AB - The ways in which epigenetic modifications fix the effects of early environmental events, ensuring sustained responses to transient stimuli that result in modified gene expression patterns and phenotypes later in life, are a topic of considerable interest. This article focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics, positions, and functions of epigenetic marks. Most epigenetic studies have addressed the long-term effects of environmental stressors on a small number of epigenetic marks, at the global or individual gene level, in humans and in animal models. In parallel, increasing numbers of studies based on high-throughput technologies are revealing additional complexity in epigenetic processes by highlighting the importance of crosstalk between different epigenetic marks in humans and mice. A number of studies focusing on metabolic programming and the developmental origin of health and disease have identified links between early nutrition, epigenetic processes, and long-term illness. The existence of a self-propagating epigenetic cycle has been shown. Moreover, recent studies have shown an obvious sexual dimorphism both for programming trajectories and in response to the same environmental insult. Despite recent progress, however, we are still far from understanding how, when, and where environmental stressors disturb key epigenetic mechanisms. Thus, the need to identify original key marks and monitor the changes they undergo throughout development, during an individual's lifetime, or over several generations remains a challenging issue. PMID- 22049165 TI - Protein requirement of healthy school-age children determined by the indicator amino acid oxidation method. AB - BACKGROUND: The current Dietary Reference Intake (DRI) recommendations for protein requirements in children are based on a factorial estimate and have not been directly determined. OBJECTIVE: The objective of the current study was to determine the protein requirement in healthy, school-age children by measuring the oxidation of L-[1-(13)C]-phenylalanine to (13)CO(2) [label tracer oxidation (F(13)CO(2))] in response to graded intakes of protein. DESIGN: Seven healthy children (6-11 y old) each randomly received a minimum of 7 protein intakes (range: 0.1-2.56 g . kg(-1) . d(-1)) for a total of 56 studies. The diets provided energy at 1.7 times the resting energy expenditure and were made isocaloric by using carbohydrate. Protein was given as an amino acid mixture on the basis of the egg-protein pattern, except for phenylalanine and tyrosine intakes, which were maintained constant across intakes. The mean protein requirement was determined by applying a 2-phase linear regression crossover analysis on F(13)CO(2) data, which identified a breakpoint (requirement) at minimal F(13)CO(2) in response to graded amounts of protein intake. RESULTS: Mean and population-safe (upper 95% CI) protein requirements were determined to be 1.3 and 1.55 g . kg(-1) . d(-1), respectively. These results are significantly higher than the mean and population-safe protein requirements currently recommended by the DRI 2005 for macronutrients (0.76 and 0.95 g . kg(-1) . d(-1), respectively). CONCLUSION: To our knowledge, this study was the first to directly estimate protein requirements in children by using stable isotopes and indicated that current recommendations are severely underestimated. PMID- 22049167 TI - Coevolution of nutrigenomics and society: ethical considerations. AB - To optimize the coevolution of nutrigenomics and society (ie, the reciprocal stimulation of both developments), I analyzed chances for a fruitful match between normative concepts and strategies of both developments. Nutrigenomics embodies >= 3 normative concepts. First, food is exclusively interpreted in terms of disease prevention. Second, striving for health is interpreted as the quantification of risks and prevention of diseases through positive food-gene interactions. The third normative idea is that disease prevention by the minimization of risks is an individual's task. My thesis was that these concepts of nutrigenomics would not easily match with concepts of food and health of various food styles in Western societies, which, for instance, parents in the case of metabolic programming endorse and with a philosophical view of the relation between food, health, and the meaning of life. Next, I reflected on the nonsynchronized coevolution of nutrigenomics and society because of this mismatch and introduced the concept of the fair representation of food styles in nutrigenomic developments. To synchronize and optimize the coevolution of nutrigenomics and society, I propose that the research policy of nutrigenomics should change to a research partnership with society on the basis of fair representation. PMID- 22049166 TI - Body fat distribution in perinatally HIV-infected and HIV-exposed but uninfected children in the era of highly active antiretroviral therapy: outcomes from the Pediatric HIV/AIDS Cohort Study. AB - BACKGROUND: Associations between abnormal body fat distribution and clinical variables are poorly understood in pediatric HIV disease. OBJECTIVE: Our objective was to compare total body fat and its distribution in perinatally HIV infected and HIV-exposed but uninfected (HEU) children and to evaluate associations with clinical variables. DESIGN: In a cross-sectional analysis, children aged 7-16 y in the Pediatric HIV/AIDS Cohort Study underwent regionalized measurements of body fat via anthropometric methods and dual-energy X-ray absorptiometry. Multiple linear regression was used to evaluate body fat by HIV, with adjustment for age, Tanner stage, race, sex, and correlates of body fat in HIV-infected children. Percentage total body fat was compared with NHANES data. RESULTS: Males accounted for 47% of the 369 HIV-infected and 51% of the 176 HEU children. Compared with HEU children, HIV-infected children were older, were more frequently non-Hispanic black, more frequently had Tanner stage >=3, and had lower mean height (-0.32 compared with 0.29), weight (0.13 compared with 0.70), and BMI (0.33 compared with 0.63) z scores. On average, HIV-infected children had a 5% lower percentage total body fat (TotF), a 2.8% lower percentage extremity fat (EF), a 1.4% higher percentage trunk fat (TF), and a 10% higher trunk-to extremity fat ratio (TEFR) than did the HEU children and a lower TotF compared with NHANES data. Stavudine use was associated with lower EF and higher TF and TEFR. Non-nucleotide reverse transcriptase inhibitor use was associated with higher TotF and EF and lower TEFR. CONCLUSION: Although BMI and total body fat were significantly lower in the HIV-infected children than in the HEU children, body fat distribution in the HIV-infected children followed a pattern associated with cardiovascular disease risk and possibly related to specific antiretroviral drugs. PMID- 22049168 TI - Joint association of glycemic load and alcohol intake with type 2 diabetes incidence in women. AB - BACKGROUND: Little is known about the joint association between glycemic index (GI), glycemic load (GL), and alcohol intake with type 2 diabetes (T2D). OBJECTIVE: The objective of this study was to examine whether alcohol intake alters the associations between carbohydrate quality (GI) or quality and quantity (GL) and T2D incidence in women. DESIGN: Participants from the Nurses' Health Study who were free of T2D, cardiovascular disease, or cancer (n = 81,827) at baseline in 1980 were followed for 26 y. Cumulative averages of GI, GL, total carbohydrates, and alcohol intake were calculated every 2-4 y from validated food frequency questionnaires. Cox proportional hazard models were used to adjust for covariates. RESULTS: We documented 6950 cases of T2D during follow-up. After adjustment for lifestyle and dietary factors, the positive association between GL and T2D risk was attenuated in subjects with higher alcohol intakes. RRs that compared the top and bottom quintiles of GL were 1.29 (95% CI: 1.11, 1.49; P trend < 0.001) in women with alcohol intakes of 0 to <5 g/d, 1.34 (95% CI: 0.93, 1.92; P-trend = 0.05) in women with alcohol intakes of 5 to <15 g/d, and 0.99 (95% CI: 0.60, 1.65; P-trend = 0.82) in women with alcohol intakes >=15 g/d (P interaction = 0.02). However, a higher intake of alcohol did not modify the positive association between GI and T2D (P-interaction = 0.76). CONCLUSION: Our findings suggest that a higher alcohol intake (>=15 g/d) attenuates the positive association between GL and T2D incidence. PMID- 22049169 TI - Long-duration space flight and bed rest effects on testosterone and other steroids. AB - CONTEXT: Limited data suggest that testosterone is decreased during space flight, which could contribute to bone and muscle loss. OBJECTIVE: The main objective was to assess testosterone and hormone status in long- and short-duration space flight and bed rest environments and to determine relationships with other physiological systems, including bone and muscle. DESIGN: Blood and urine samples were collected before, during, and after long-duration space flight. Samples were also collected before and after 12- to 14-d missions and from participants in 30- to 90-d bed rest studies. SETTING: Space flight studies were conducted on the International Space Station and before and after Space Shuttle missions. Bed rest studies were conducted in a clinical research center setting. Data from Skylab missions are also presented. PARTICIPANTS: All of the participants were male, and they included 15 long-duration and nine short-duration mission crew members and 30 bed rest subjects. MAIN OUTCOME MEASURES: Serum total, free, and bioavailable testosterone were measured along with serum and urinary cortisol, serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and SHBG. RESULTS: Total, free, and bioavailable testosterone was not changed during long-duration space flight but were decreased (P < 0.01) on landing day after these flights and after short-duration space flight. There were no changes in other hormones measured. Testosterone concentrations dropped before and soon after bed rest, but bed rest itself had no effect on testosterone. CONCLUSIONS: There was no evidence for decrements in testosterone during long-duration space flight or bed rest. PMID- 22049171 TI - Clinical implications of the ACCORD trial. AB - CONTEXT: The Action to Control Cardiovascular Risk in Type 2 Diabetes (ACCORD) was a double factorial randomized clinical trial comparing intensive vs. standard glycemic control, intensive versus standard blood pressure control and fenofibrate versus placebo against a background of statin treatment. EVIDENCE: The primary outcome of cardiovascular disease (CVD), a composite of CVD death, non-fatal myocardial infarction and non-fatal stroke was not reduced by either of the intensive strategies or by addition of fenofibrate; moreover, total mortality was increased by the intensive glycemic strategy. Some secondary CVD outcomes were benefited as were some secondary microvascular outcomes by the more aggressive treatments. Epidemiological analyses were perplexing: for example, earlier severe hypoglycemic episodes were a risk factor for mortality and occurred three times as often in the intensive glycemic treatment group, but the excess of deaths in that group was not accounted for by those subjects who had suffered earlier episodes of severe hypoglycemia. CONCLUSIONS: Despite such perplexing results, some clinical implications that can be drawn from the kaleidoscope of ACCORD findings are offered here. Cases are suggested where intensive blood pressure treatment or addition of fenofibrate to statin therapy may be warranted, whereas intensive glycemic therapy is rarely, if ever, justified in ACCORD type patients. PMID- 22049170 TI - Ectopic lipid accumulation and reduced glucose tolerance in elderly adults are accompanied by altered skeletal muscle mitochondrial activity. AB - CONTEXT: Aging is associated with insulin resistance and unfavorable changes in body composition including increased fat accumulation, particularly in visceral and ectopic depots. Recent studies suggest that skeletal muscle mitochondrial activity may underlie some age-associated metabolic abnormalities. OBJECTIVE: Our objective was to measure mitochondrial capacity and coupling of the vastus lateralis muscle in elderly and young adults using novel in vivo approaches and relate mitochondrial activity to metabolic characteristics. DESIGN: This was a cross-sectional study. PARTICIPANTS AND INTERVENTION: Fourteen sedentary young (seven males and seven females, 20-34 yr of age) and 15 sedentary elderly (seven males and eight females, 70-84 yr of age) nonobese subjects selected for similar body weight underwent measures of body composition by magnetic resonance imaging and dual-energy x-ray absorptiometry, oral glucose tolerance, and in vivo mitochondrial activity by (31)P magnetic resonance and optical spectroscopy. Muscle biopsy was carried out in the same muscle to measure mitochondrial content, antioxidant activity, fiber type, and markers of mitochondrial biogenesis. RESULTS: Elderly volunteers had reduced mitochondrial capacity (P = 0.05) and a trend for decreased coupling efficiency (P = 0.08) despite similar mitochondrial content and fiber type distribution. This was accompanied by greater whole-body oxidative stress (P = 0.007), less skeletal muscle mass (P < 0.001), more adipose tissue in all depots (P <= 0.002) except intramyocellular (P = 0.72), and lower glucose tolerance (P = 0.07). CONCLUSIONS: Elderly adults show evidence of altered mitochondrial activity along with increased adiposity, oxidative stress, and reduced glucose tolerance, independent of obesity. We propose that mild uncoupling may be induced secondary to age-associated oxidative stress as a mechanism to dissipate the proton-motive force and protect against further reactive oxygen species production and damage. PMID- 22049172 TI - Circulating anti-Mullerian hormone levels in adult men are under a strong genetic influence. AB - CONTEXT: The determinants of serum anti-Mullerian hormone (AMH) levels in adult men remain unclear. OBJECTIVE: The objective of the study was to investigate the genetic and environmental components in determining postpubertal AMH levels in healthy men. DESIGN AND PARTICIPANTS: Serum AMH levels, body mass index (BMI), and fat mass (dual energy x-ray absorptiometry) were measured in 64 healthy male (23 monozygotic and 41 dizygotic) twin pairs. RESULTS: Postpubertal AMH levels were highly genetically determined (broad sense heritability 0.92, 95% confidence interval 0.83-0.96). AMH correlated negatively with BMI (r = -0.26, P = 0.030) and fat mass (r = -0.23, P = 0.048). As AMH, BMI had a high heritability (0.68, 95% confidence interval 0.39-0.83), but no genetic correlation was observed between them. CONCLUSIONS: AMH levels in men after puberty are under a strong genetic influence. Twin modeling suggests that AMH and BMI are influenced by different sets of genes. PMID- 22049173 TI - Frequent TSH receptor genetic alterations with variable signaling impairment in a large series of children with nonautoimmune isolated hyperthyrotropinemia. AB - CONTEXT: Heterozygous mutations in the TSH receptor gene (TSHR) are associated with partial TSH resistance, characterized by isolated nonautoimmune hyperthyrotropinemia (NAHT). The prevalence and management of this condition is controversial. OBJECTIVE: Our objective was to investigate the prevalence and clinical impact of TSHR alterations in a large series of pediatric patients with NAHT and to dissect their mechanism of action. DESIGN AND SETTING: For this prospective multicenter study, clinical data and samples were collected in the clinical units and conveyed to a centralized laboratory for analysis. PATIENTS: Subjects included 153 unrelated patients with NAHT aged <18 yr. Exclusion criteria included thyroid dysgenesis or major associated congenital defects. MAIN OUTCOME MEASURES: Parameters of thyroid function, TSHR gene analysis, and TSHR functional assays were evaluated. RESULTS: The frequency of heterozygous nonpolymorphic TSHR variations was 11.8%. We identified seven previously unknown variations: a frameshift (p.Q33PfsX46), one intronic (g.IVS4+2A->G), and five novel missense (p.P162L, p.Y466C, p.I583T, p.I607T, and p.R609Q) variations. The missense variations variably affected TSHR membrane expression and G(s) and/or G(q/11) signaling. Several variations cosegregated with NAHT in the affected families. Parameters of thyroid function were similar between affected and unaffected family members. CONCLUSIONS: Nonpolymorphic alterations in the TSHR gene are commonly associated with isolated NAHT in young patients, thus configuring partial TSH resistance as the most frequent inheritable cause of isolated NAHT. The identification of TSHR defects may thus be helpful for a tailored management of subclinical hypothyroidism. We provide further evidence that besides the well-known defects in G(s) signaling, TSHR genetic alternations found in NAHT may frequently impair the G(q/11) pathway. PMID- 22049174 TI - Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves' disease. AB - CONTEXT: Although antithyroid drug (ATD)-induced hematopoietic damage is a significant concern, it has not been comprehensively investigated. OBJECTIVE: Our objective was to describe the clinical features of ATD-induced hematopoietic damage. DESIGN AND SETTING: This was a retrospective cohort study in Tokyo, Japan. PATIENTS: Between January 1983 and December 2002, 50,385 patients at Ito Hospital were diagnosed with Graves' disease. We retrospectively reviewed their medical, pathological, and laboratory records between January 1983 and December 2010. MAIN OUTCOME: Incidence and clinical features of ATD-induced agranulocytosis and pancytopenia were evaluated. RESULTS: Of 55 patients with documented hematopoietic damage, 50 had agranulocytosis and 5 had pancytopenia. All of them received ATD, either methimazole (n = 51) or propylthiouracil (n = 4). Median intervals between initiation of ATD therapy and the onset of agranulocytosis and pancytopenia were 69 d (range, 11-233 d) and 41 d (range, 32 97 d), respectively. Either anemia or thrombocytopenia was also documented in seven of the 50 patients with agranulocytosis. Agranulocytosis was the first manifestation of hematopoietic damage in four of the five patents with pancytopenia. Hematopoietic damage recovered with supportive measures including granulocyte colony-stimulating factor (n = 37), steroids (n = 10), and other supportive measures (n = 8) in 54 patients, whereas the remaining patient died of complications from infection. This study failed to identify the risk factors for ATD-induced hematopoietic damage. CONCLUSIONS: This study showed that ATD cause hematopoietic changes, which are occasionally severe and potentially fatal. The pathogenesis of agranulocytosis and pancytopenia might overlap, and additional studies are warranted to clarify this and to establish an optimal treatment strategy. PMID- 22049175 TI - FoxM1 and its association with matrix metalloproteinases (MMP) signaling pathway in papillary thyroid carcinoma. AB - CONTEXT: Forkhead boxM1 (FoxM1) transcription factor has been shown to promote pathogenesis of several malignancies. FoxM1 has also been shown to be associated with matrix metalloproteinases (MMP) in various cancers. However, little is known about its function in papillary thyroid carcinoma (PTC). OBJECTIVE: In this study, we investigated the role of FoxM1 in pathogenesis in a large series of PTC in a tissue microarray format followed by in vitro and in vivo studies using PTC cell lines and nude mice. DESIGN: Expression of FoxM1 and its associated proteins were investigated in Middle Eastern PTC samples by immunohistochemistry. Apoptosis was measured by flow cytometry and immunoblotting. Invasion and migration studies were performed using 8-MUm Transwell plates. RESULTS: FoxM1 was overexpressed in 28.4% of PTC and significantly associated with activated matrix metalloproteinase-9 (MMP-9) (P = 0.0004), X-linked inhibitor of apoptosis protein (XIAP) (P = 0.0024), and B-cell lymphoma-extra large (Bcl-XL) (P = 0.0014) expression. Treatment of PTC cell lines with thiostrepton, an inhibitor of FoxM1, resulted in inhibition of cell viability via induction of apoptosis. In addition, thiostrepton treatment of PTC cells or expression of FoxM1-specific small interfering RNA down-regulated expression of FoxM1 accompanied with decreased MMP 2 and MMP-9 expression. Furthermore, inhibition of FoxM1 attenuated migration and invasion of PTC cells. Interestingly, overexpression of FoxM1 rescued the effects of thiostrepton in PTC cell lines. Finally, treatment of PTC cell line xenografts with thiostrepton resulted in growth inhibition of tumors in nude mice via down regulation of FoxM1 and MMP-9 and MMP-2. CONCLUSION: Altogether, this is the first study showing that FoxM1 and its associated signaling pathway play a critical role in the pathogenesis of PTC and may be a potential target for therapeutic intervention for treatment of these cancers. PMID- 22049176 TI - Paradoxical clearance of natriuretic peptide between pulmonary and systemic circulation: a pulmonary mechanism of maintaining natriuretic peptide plasma concentration in obese individuals. AB - CONTEXT: Although it has been reported that obese patients have low levels of natriuretic peptide, the metabolism of natriuretic peptide in this population remains unclear. OBJECTIVES: This study aimed to examine the effects of body mass index on the natriuretic peptide clearance rate from the pulmonary and systemic circulation. DESIGN: We conducted a prospective observational cohort study. SETTING/PATIENTS: Thirty patients with atrial fibrillation undergoing pulmonary vein isolation in single center participated in the study. MAIN OUTCOMES AND MEASURES: We measured pulmonary and systemic atrial/brain natriuretic peptide clearance and clinical parameters including body mass index and pulmonary oxygen levels. RESULTS: Significantly lower atrial natriuretic peptide levels were found in all pulmonary veins when compared with the pulmonary artery. The pulmonary atrial natriuretic peptide clearance rate was negatively correlated with body mass index. In contrast, the systemic atrial natriuretic peptide clearance rate was positively correlated with the body mass index. A reciprocal relationship therefore exists between pulmonary and systemic atrial natriuretic peptide clearance. Regional pulmonary atrial natriuretic peptide clearances in the inferior lung were significantly negatively correlated to oxygen pressure in the inferior pulmonary veins. There was a similar tendency for brain natriuretic peptide, but the differences between the pulmonary artery and each pulmonary vein were not significant. CONCLUSIONS: Overweight patients have higher systemic atrial natriuretic peptide clearance, whereas they show a lower pulmonary atrial natriuretic peptide clearance, which might be related to pulmonary tissue hypoxia. PMID- 22049177 TI - Diets higher in dairy foods and dietary protein support bone health during diet- and exercise-induced weight loss in overweight and obese premenopausal women. AB - CONTEXT: Consolidation and maintenance of peak bone mass in young adulthood may be compromised by inactivity, low dietary calcium, and diet-induced weight loss. OBJECTIVE: We aimed to determine whether higher intakes of dairy foods, dietary calcium, and protein during diet- and exercise-induced weight loss affected markers of bone health. PARTICIPANTS: Participants included premenopausal overweight and obese women. DESIGN/INTERVENTION: Ninety participants were randomized into three groups (n = 30 per group): high protein and high dairy (HPHD), adequate protein and medium dairy (APMD), and adequate protein and low dairy (APLD), differing in dietary protein (30, 15, or 15% of energy, respectively), dairy foods (15, 7.5, or <2% of energy from protein, respectively), and dietary calcium (~1600, ~1000, or <500 mg/d, respectively). OUTCOME MEASURES: Serum and urine bone turnover biomarkers, serum osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), PTH, 25 hydroxyvitamin D, leptin, and adiponectin measured at 0 and 16 wk. RESULTS: All groups lost equivalent body weight (P < 0.05). N-telopeptide, C-telopeptide (CTX), urinary deoxypyridinoline, and osteocalcin increased in APLD (P < 0.01), whereas in HPHD, osteocalcin and procollagen 1 amino-terminal propeptide (P1NP) increased (P < 0.05), and all resorption markers remained unchanged. P1NP to CTX and OPG to RANKL ratios increased in HPHD (P < 0.005), and P1NP to CTX ratio decreased in APLD (P < 0.05). PTH decreased in HPHD and APMD vs. APLD (P < 0.005), and 25-hydroxyvitamin D increased in HPHD (P < 0.05), remained unchanged in APMD, and decreased in APLD (P < 0.05). Leptin decreased and adiponectin increased in APMD and HPHD only (P < 0.001). CONCLUSIONS: Hypoenergetic diets higher in dairy foods, dietary calcium, and protein with daily exercise, favorably affected important bone health biomarkers vs. diets with less of these bone-supporting nutrients. PMID- 22049178 TI - Variants of the adiponectin and adiponectin receptor-1 genes and posttransplantation diabetes mellitus in renal allograft recipients. AB - CONTEXT: Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients. Adiponectin (ADIPOQ) and adiponectin receptor-1 (ADIPOR1) gene polymorphisms have been associated with type 2 diabetes. However, it is unknown whether these polymorphisms are also risk factors for PTDM. OBJECTIVE: We investigated the association between PTDM and single-nucleotide polymorphisms of ADIPOQ and ADIPOR1 in a cohort of renal allograft recipients. DESIGN, SETTING, AND PARTICIPANTS: Five hundred seventy five patients (367 men and 208 women) who received kidney transplants between 1989 and 2007, without a history of diabetes and with a pretransplant fasting glucose concentration less than 5.5 mmol/liter. Patients were followed up for a median 10 yr. Genotypes included single-nucleotide polymorphisms of the following: ADIPOQ rs266729, rs822395, rs822396, rs2241766, and rs1501299 and ADIPOR1 rs2232853, rs12733285, and rs1342387. RESULTS: TT-homozygotes in ADIPOQ rs1501299 [hazard ratio (HR) = 1.70, P = 0.032] had greater risk of PTDM after adjusting for age, sex, amount of weight gain, and type of immunosuppressant. There was a significant interaction between sex and ADIPOQ rs1501299 genotype (P = 0.037). In men, but not in women, TT-homozygotes in ADIPOQ rs1501299 were more likely to develop PTDM than the wild GG-homozygotes (HR = 2.50, P = 0.002), whereas GT-heterozygotes had nonsignificantly elevated risk (HR = 1.41, P = 0.128). CONCLUSION: Genetic variation in ADIPOQ rs1501299 is associated with PTDM in a sex-specific manner. PMID- 22049179 TI - Gonadotropin responses to estrogen-positive and -negative feedback are identical in African-American and Caucasian women. AB - CONTEXT: Gonadotropin levels are similar in African-American women (AAW) and Caucasian women (CW), despite higher preovulatory estradiol (E2) levels in AAW, suggesting that AAW may be less sensitive to E2 feedback than CW. OBJECTIVE: The aim of the study was to determine whether responsivity to estrogen feedback differs in AAW and CW. DESIGN AND SETTING: Subjects were studied in the early follicular phase using a 5-d, graded E2 and progesterone infusion. SUBJECTS: Healthy, normal-cycling AAW (n = 10) and CW (n = 13) aged 23-30 yr participated in the study. MAIN OUTCOME MEASURES: Blood samples were collected every 4 h and assayed for LH, FSH, E2, and progesterone. RESULTS: There was no difference in E2 negative feedback on LH (nadir, 3.8 +/- 0.4 vs. 5.4 +/- 0.9 IU/liter; time of nadir, 33.2 +/- 3.3 vs. 32.3 +/- 2.7 h) or FSH (nadir, 3.1 +/- 0.4 vs. 3.1 +/- 0.3 IU/liter; time of nadir, 48.8 +/- 2.7 vs. 50.5 +/- 3.1 h) in AAW compared to CW. The two groups also demonstrated similar positive feedback responses of E2 on LH (peak, 80.3 +/- 13.3 vs. 73.1 +/- 11.6 IU/liter; time of peak, 80.4 +/- 4.3 vs. 86.5 +/- 3.1 h) and FSH (peak, 13.4 +/- 1.4 vs. 10.2 +/- 1.0 IU/liter; time of peak, 82.2 +/- 4.0 vs. 97.2 +/- 4.9 h). CONCLUSIONS: LH and FSH feedback responses to a controlled steroid infusion do not differ between AAW and CW, indicating that AAW do not have diminished hypothalamic-pituitary responsivity to E2. These studies support the concept of a threshold effect of E2 in generating LH-positive feedback, suggest pituitary insensitivity to differences in E2 of the magnitude observed in prior studies, and account for similarities in gonadotropins despite E2 differences in AAW compared with CW. PMID- 22049180 TI - Serum TSH within the reference range as a predictor of future hypothyroidism and hyperthyroidism: 11-year follow-up of the HUNT Study in Norway. AB - CONTEXT: Serum TSH in the upper part of the reference range may sometimes be a response to autoimmune thyroiditis in early stage and may therefore predict future hypothyroidism. Conversely, relatively low serum TSH could predict future hyperthyroidism. OBJECTIVE: The objective of the study was to assess TSH within the reference range and subsequent risk of hypothyroidism and hyperthyroidism. DESIGN AND SETTING: This was a prospective population-based study with linkage to the Norwegian Prescription Database. SUBJECTS: A total of 10,083 women and 5,023 men without previous thyroid disease who had a baseline TSH of 0.20-4.5 mU/liter and who participated at a follow-up examination 11 yr later. MAIN OUTCOME MEASURES: Predicted probabilities of developing hypothyroidism or hyperthyroidism during follow-up, by categories of baseline TSH, were estimated. RESULTS: During 11 yr of follow-up, 3.5% of women and 1.3% of men developed hypothyroidism, and 1.1% of women and 0.6% of men developed hyperthyroidism. In both sexes, the baseline TSH was positively associated with the risk of subsequent hypothyroidism. The risk increased gradually from TSH of 0.50-1.4 mU/liter [women, 1.1%, 95% confidence interval (CI) 0.8-1.4; men, 0.3%, 95% CI 0.1-0.6] to a TSH of 4.0-4.5 mU/liter (women, 31.5%, 95% CI 24.6-39.3; men, 14.7%, 95% CI 7.7 26.2). The risk of hyperthyroidism was higher in women with a baseline TSH of 0.20-0.49 mU/liter (3.9%, 95% CI 1.8-8.4) than in women with a TSH of 0.50-0.99 mU/liter (1.4%, 95% CI 0.9-2.1) or higher (~1.0%). CONCLUSION: TSH within the reference range is positively and strongly associated with the risk of future hypothyroidism. TSH at the lower limit of the reference range may be associated with an increased risk of hyperthyroidism. PMID- 22049181 TI - Impaired exercise performance and muscle Na(+),K(+)-pump activity in renal transplantation and haemodialysis patients. AB - BACKGROUND: We examined whether abnormal skeletal muscle Na(+),K(+)-pumps underlie impaired exercise performance in haemodialysis patients (HDP) and whether these are improved in renal transplant recipients (RTx). METHODS: Peak oxygen consumption ( O(2peak)) and plasma [K(+)] were measured during incremental exercise in 9RTx, 10 HDP and 10 healthy controls (CON). Quadriceps peak torque (PT), fatigability (decline in strength during thirty contractions), thigh muscle cross-sectional area (TMCSA) and vastus lateralis Na(+),K(+)-pump maximal activity, content and isoform (alpha(1)-alpha(3), beta(1)-beta(3)) abundance were measured. RESULTS: O(2peak) was 32 and 35% lower in RTx and HDP than CON, respectively (P < 0.05). PT was less in RTx and HDP than CON (P < 0.05) but did not differ when expressed relative to TMCSA. Fatigability was ~1.6-fold higher in RTx (24 +/- 11%) and HDP (25 +/- 4%) than CON (15 +/- 5%, P < 0.05). Na(+),K(+) pump activity was 28 and 31% lower in RTx and HDP, respectively than CON (P < 0.02), whereas content and isoform abundance did not differ. Pooled (n = 28) O(2peak) correlated with Na(+),K(+)-pump activity (r = 0.45, P = 0.02). CONCLUSIONS: O(2peak) and muscle Na(+),K(+)-pump activity were depressed and muscle fatigability increased in HDP, with no difference observed in RTx. These findings are consistent with the possibility that impaired exercise performance in HDP and RTx may be partially due to depressed muscle Na(+),K(+)-pump activity and relative TMCSA. PMID- 22049182 TI - Urine neutrophil gelatinase-associated lipocalin identifies unilateral and bilateral urinary tract obstruction. AB - BACKGROUND: Urinary tract obstruction (UTO) is a common problem that can lead to permanent loss of kidney function. Unilateral UTO may be difficult to diagnose. Urinary neutrophil gelatinase-associated Lipocalin (uNGAL) may identify unilateral and bilateral UTO. METHODS: Retrospective case-control study of patients undergoing hospital admission at three sites. UTO was determined by review of medical records and cases were matched to control patients. uNGAL was measured by immunoblot. RESULTS: Twenty-four unilateral UTO and 15 bilateral UTO cases were identified. Admission serum creatinine (sCr) (milligram per decilitre) was significantly higher in bilateral UTO, 2.0 (1.1-5.3), but not unilateral UTO, 1.1 (0.8-1.5), compared to controls, 0.9 (0.8-1.2). uNGAL (nanogram per millilitre) was significantly higher both in patients with bilateral UTO, 140 (40 450), and unilateral UTO, 50 (20-100), compared to controls, 20 (10-45). DISCUSSION: uNGAL identifies kidney injury in unilateral and bilateral UTO even in the absence of an elevated sCr. PMID- 22049183 TI - Beneficial effects of integrin alphavbeta3-blocking RGD peptides in early but not late phase of experimental glomerulonephritis. AB - BACKGROUND: Integrin alphavbeta3 plays an important role in the regulation of cell proliferation and neoangiogenesis. We found mesangial de novo expression of integrin alphavbeta3 in mesangioproliferative glomerulonephritis (MesGN). The aim of the study was to clarify if blockade of alphavbeta3 integrin with the specific alphavbeta3-blocking cyclic peptide RGDdFV (cRGD) has beneficial effects on the course of this disease. METHODS: Habu snake venom (Habu) GN was induced in male C57BL/6 mice 1 week after uninephrectomy (6 mg Habu toxin/kg body weight intravenously). After 24 h, nephritic animals received alphavbeta3-inhibitory cRGD or cRAD control peptides for 3 or 7 days, respectively. The kidneys were investigated using morphometry, immunohistochemistry and TaqMan polymerase chain reaction. RESULTS: At Day 3, serum creatinine and albuminuria were lower after cRGD compared to cRAD treatment. At Day 3, glomerulosclerosis index, percentage of glomerular injury, mesangial cell (MC) number and volume density of mesangial matrix were significantly lower (P < 0.05) in cRGD-treated mice than in cRAD treated controls. At Day 7, only a mild effect of cRGD on mesangial matrix expansion and fibronectin messenger RNA was still detectable (P < 0.05). Complementary in vitro studies in MCs revealed that inhibition of alphavbeta3 by cRGD-blocked adhesion, reduced proliferation and increased apoptosis of MCs. CONCLUSION: Habu GN inhibition of integrin alphavbeta3 by cRGD partly ameliorates early injury but has no or only mild effects on late glomerular lesions. PMID- 22049185 TI - Editorial. PMID- 22049186 TI - The social relations-physical health connection: a comparison of elderly samples from the United States and Japan. AB - Cross-national comparison of the social relations-physical health association in the elderly can broaden our understanding of the implications of social relationships in this age group. Using representative cross-sectional samples of adults aged 60-93 years from metropolitan areas in the United States and Japan (n = 1005), we used analysis of variance to examine between-country differences in the association of illness with measures of network structure, social support, and negative relations. One significant between-country difference in this association was found: in Japan only, ill women reported more available financial help from their child than did non-ill women (p < .05). Ill women in both countries reported less sick care available from their spouse than did ill men (p < .05) and more negative relations with their child than did non-ill women (p < .05). These results suggest the primacy of gender, rather than cultural context, in shaping the association between social relations and health. PMID- 22049184 TI - Efficacy and safety of regional citrate anticoagulation in liver transplant patients requiring post-operative renal replacement therapy. AB - BACKGROUND: Liver transplant patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) early post-operatively are at high risk for bleeding. Using heparin for anticoagulation during CRRT may contribute to the increased bleeding risk. Regional anticoagulation with citrate may decrease the risk of bleeding. However, citrate anticoagulation may be associated with metabolic complications in patients with liver impairment. The aim of the study was to evaluate the safety and efficacy of citrate anticoagulation in liver transplant patients. METHODS: All liver transplant recipients transplanted between November 2004 and August 2007, requiring CRRT and using citrate as the anticoagulant were included in this retrospective study. Demographic data, CRRT specific and metabolic data were collected and analysed. RESULTS: Sixty-eight patients (40 male/28 female) with a mean age of 47.1+/-11.8 years and a Model of End-stage Liver Disease score of 23+/-9 developed post-operative AKI requiring CRRT using citrate as the anticoagulant. The median duration on CRRT was 8 days (range 1-39 days) with a mean circuit life of 22.7+/-14.6 h. There was no relevant time trend of serum sodium, potassium, calcium, bicarbonate and pH values during CRRT. Bleeding occurred in 8 of 68 (11.7%) patients during CRRT. CONCLUSION: Regional citrate anticoagulation for CRRT in the early post-operative period after liver transplantation is effective and safe. Therefore, the general exclusion of citrate anticoagulation during CRRT in patients after liver transplantation is not justified. PMID- 22049187 TI - Anger expression and natural killer cell activity in family caregivers participating in a physical activity trial. AB - Associations between psychological functioning and natural killer cell activity (NKA) were examined in 23 older (62.2 +/- 7.5 years) family caregivers randomized to a moderate intensity four-month exercise program or to a wait-list control condition. At baseline, although NKA was related to anger-control (r = -.42; trend p < .06) and anger-out (r = .50; p < .03), it was not related to depression, anxiety, perceived stress, or caregiver burden. After controlling for baseline NKA, changes in anger-control explained 14 percent of the variance in NKA four months later. Decreases in anger-control predicted increases in NKA. Group assignment (exercise vs control) was unrelated to changes in NKA over the four-month period; however, the study was not powered to detect this effect. These results are consistent with reported relationships of anger expression with other physiological measures, and extend the importance of anger expression to immune functioning in older family caregivers. PMID- 22049188 TI - Self-perceptions and Current Practices of High-risk Older Drivers: Implications for Driver Safety Interventions. AB - Many older drivers with visual problems meet the legal requirements for licensing despite having functional impairments that elevate crash risk. In a sample of visually impaired older drivers, over half believed that their vision was not likely to cause them to crash. Eighty percent acknowledged that they would feel more protected against crashing if they avoided certain driving situations. However, 75 percent of the sample reported never or rarely avoiding such situations (e.g. left turns, interstate highways). Almost 70 percent of drivers reported high self-efficacy in their ability to self-regulate and use alternative strategies. These data imply that behavioral interventions promoting compensatory strategies of self-regulation may be useful in maintaining mobility while improving the safety of high-risk older drivers. These findings serve as baseline for our ongoing study evaluating whether an educational intervention will increase self-regulation and improve older driver safety. PMID- 22049189 TI - Anticipated choices among self-, informal, and formal care by older canadians. AB - The present research investigated factors related to the health care choices seniors anticipated making in response to hypothetical illness symptoms (e.g. rectal bleeding). After collecting demographic data, 80 seniors were presented various illness symptoms. Directly following each symptom they were asked whether they anticipated using self-, informal, or formal care to deal with the potential problem. In general, seniors with higher perceived health status anticipated using self-care. Being male and having a lower perceived health status was predictive of choosing informal care, whereas being female was predictive of anticipating using formal care. When individual symptoms were analyzed, additional predictors were identified. Judged seriousness of a symptom, experience with a symptom, and social network status were related to different anticipated health care choices for some, but not all, symptoms. Perhaps the most striking finding was the difference between males and females. Since health status between males and females was not significantly different, this difference in anticipated choice of care seemed to be linked to personal preference rather than health status per se. PMID- 22049190 TI - Health, fear of crime and psychosocial functioning in older people. AB - Fear of crime is thought to limit social activity in older people. Sixty older people, recruited via day centres, were given questionnaire-based interviews. A series of questions produced two scales of crime awareness and a scale of perceived crime prevalence. Fear of crime was operationalized through a catastrophizing technique, and by a single-item measure of perceived safety. Physical health, mental health and psychosocial limitation were assessed. Physical health was found to moderate a relationship between crime awareness and fear of crime. In multivariate models, fear of crime was not a significant predictor of psychosocial limitation, which was predicted by physical and mental health. Implications of the findings for models of fear of crime and health psychology are discussed. PMID- 22049191 TI - Educational Status and Risk of HIV in Young Gay Men. AB - Lower socioeconomic status (SES) has been associated with higher rates of HIV infection as well as higher rates of unsafe sex. The behavioral determinants that might mediate the effect of SES on risky sex have not been studied thus far. We investigated the involvement of social cognitions in the link between educational status and unprotected anal sex in 292 participants of the Amsterdam Young Gay Men Study. We found that poorly educated men had poorer knowledge about HIV and preventive behavior, perceived social norms to be less favorable towards condom usage with casual partners, and had lower perceived control over that behavior than the better educated men. Poorly educated men were also more likely to have engaged in unprotected anal sex with casual partners in the six-month period that followed the assessment of the social cognitions. However, the education-related behavioral difference could not be explained by social cognitions. We concluded that cognitive models of behavior might not explain all of the risk behavior in gay men with lower SES. These men's risk-taking behavior might result from specific psychological characteristics of men with lower SES that interfere with traditional cognition-behavior correlations as posited in prevailing models of behavior. PMID- 22049192 TI - Psychosocial Issues in the Era of New AIDS Treatments from the Perspective of Persons Living with HIV. AB - In the past, HIV disease meant an almost invariably downward health course. New highly active antiretroviral therapy (HAART) regimens have improved the health outlook for many persons living with HIV/AIDS but may create new psychological and coping challenges. In this study, open-ended, in-depth interviews were undertaken with an ethnically diverse sample of 44 purposively selected men and women with HIV disease who were on HAART regimens. The interviews were transcribed and qualitatively coded to identify major themes. While patients responding well to the regimens held optimistic views for their future, some who continued to have detectable viral load exhibited depression and feelings of hopelessness. Many patients reported stress associated with the demands of adhering to complex HAART regimens. Other common themes emerging in the interviews involved concerns about employment, romantic and non-romantic relationship formation, sexual behavior and serostatus disclosure, whether to plan families, and experiences of AIDS-related discrimination. There continue to be critical roles for psychological services in the care of persons living with HIV. PMID- 22049193 TI - Coping with Negative Emotions: The Cognitive Strategies of HIV-infected Gay/Bisexual Men. AB - While the managing of negative emotions has been identified as a central adaptive task for those living with chronic illnesses such as HIV/AIDS, little is known about the specific coping strategies used to achieve this task. The present study employed unstructured interviews to examine illnessspecific cognitive strategies used by an ethnically diverse sample of HIV-infected men who have sex with men (MSM) in their attempts to manage the negative emotions associated with the illness. Fourteen specific cognitive strategies were identified, many of which were specific to coping with chronic illness or HIV/AIDS. These strategies were categorized into four major conceptual categories: (1) distancing the threat of death; (2) reducing the sense of victimization; (3) gaining a sense of control; and (4) mentally preparing for emotional upset. The findings have implications for what coping assessments may be neglecting and may provide insights for therapeutic application. PMID- 22049194 TI - Managing the Impact of Illness: The Experiences of Men with Prostate Cancer and their Spouses. AB - This qualitative study explored issues of support and coping for couples where the man had been diagnosed with prostate cancer. Thirty-four men with prostate cancer and their spouses were interviewed separately at three points in time: prior to surgery; 8 to 10 weeks post-surgery; and 11 to 13 months post-surgery. The core category for the couples' experience with diagnosis and treatment for prostate cancer was Managing the Impact of Illness. Five major domains emerged, including: dealing with the practicalities; stopping illness from interfering with everyday life; keeping relationships working; managing feelings; and making sense of it all. While it was clearly important for couples to manage illness and to reduce its potential intrusion into everyday life, this strategy had psychological costs as well as benefits. Men struggled to stay in control of their emotions and their lives, typically vacillating between the pulls of fierce self-reliance and fearful neediness. Women were constrained from employing their usual strategies of coping and were distressed by the complicated requirements of being supportive while also honoring their partners' need for self-reliance. PMID- 22049195 TI - Employment status and health in young adults: economic and behavioural mediators? AB - In a sample of young Canadian adults, questionnaire data indicated that both unemployment and selfreported underemployment represent health risks, as defined by subjectively rated health, experienced symptoms and illness measures. While health behaviours, including substance use, diet and exercise, medical compliance and unsafe driving practices contributed independently to health outcomes, they did not explain the linkage between employment status and health. Household income, but not personal income, predicted health and mediated this relationship only in the case of symptoms. The results are discussed in terms of an expanded understanding of the socioeconomic gradient in health. PMID- 22049196 TI - Handedness and age of death: new evidence on a puzzling relationship. AB - Based on 5743 deaths in the United States and Canada, the present study was undertaken to verify and extend results suggesting that left handers have a shorter life expectancy than right handers. Unlike previous studies, which have merely dichotomized handedness, this study used a 5-point scale to measure handedness (extremely right handed, generally right handed, ambidextrous, generally left handed and extremely left handed). We found a significant tendency for one of the five handedness categories-those classified as generally left handers-to die at a significantly younger age than was true for the other four handedness groups. Our findings add to the controversy over links between handedness and age of death by suggesting that only a portion of left handers are at risk of premature death. PMID- 22049197 TI - Motivations for Anabolic Steroid use Among Bodybuilders. AB - Steroid use is increasing, in parallel with rising concerns about body image. This study aimed to uncover bodybuilders' motivations for using steroids using 135 questionnaires completed by readers of two bodybuilding magazines. The analyses reveal a polarization of beliefs about steroids between users and non users. Steroid users were less likely to be concerned about the physical side effects, and many believed that steroids are not harmful in moderation, and that only 'ignorant people' criticize steroid use. Their main motivations for using steroids were: wanting to excel at competitive bodybuilding; wanting to be more muscular; and feelings of enhanced confidence. The fact that steroid users in the sample were 'stacking' dangerously high levels of steroids (up to 15 steroids at a time) reveals the need for a detailed understanding of the motivations for steroid use in order to inform the development of effective harm minimization messages. PMID- 22049199 TI - Annual index. PMID- 22049200 TI - Neuropathy in Parkinson disease: prevalence and determinants. AB - OBJECTIVE: To ascertain the prevalence and determinants of neuropathy in patients with Parkinson disease (PD), in particular, the roles of vitamin B12 and levodopa exposure. METHODS: We performed a cross-sectional study of 37 patients with PD and 37 age- and gender-matched controls, using a sensitive and validated neuropathy scale. The prevalence of neuropathy was determined and compared between groups. We then ascertained the role of vitamin B12 by a separate case control analysis (1) comparing numbers of patients in whom the neuropathy was directly attributable to vitamin B12 deficiency and (2) comparing serum vitamin B12 levels in patients with PD with neuropathy with a second control group consisting of age- and gender-matched consecutive patients with neuropathy without PD. We also determined correlations between cumulative levodopa exposure, PD duration, neuropathy status and score, and vitamin B12 status and levels in all patients with PD and, specifically, in those with neuropathy. RESULTS: Fourteen of 37 (37.8%) patients with PD and 3 of 37 (8.1%) control subjects had neuropathy (p = 0.005), corresponding to an odds ratio (95% confidence interval) for neuropathy, of 6.9 (1.78-26.73). Vitamin B12 deficiency was a significantly more common cause of neuropathy (p = 0.024) and vitamin B12 levels were significantly lower (p = 0.002) in patients with PD with neuropathy than in age- and gender-matched consecutive control subjects with neuropathy without PD. Cumulative levodopa exposure correlated with PD duration (p = 0.001) and vitamin B12 levels (p = 0.044), in patients with PD with neuropathy. CONCLUSIONS: Neuropathy is more prevalent in patients with PD than in control subjects. This may be predominantly due to vitamin B12 deficiency, which could relate to cumulative levodopa exposure in susceptible individuals. Vitamin B12 monitoring and supplementation, as well as serial clinical assessment for neuropathy, may be advisable in patients with PD. PMID- 22049201 TI - Pentanucleotide repeats at the spinocerebellar ataxia type 31 (SCA31) locus in Caucasians. PMID- 22049202 TI - Parkinson disease, L-dopa, and neuropathy: did we miss something? PMID- 22049203 TI - Intravenous dihydroergotamine for inpatient management of refractory primary headaches. AB - OBJECTIVE: To determine dosing and side effects of dihydroergotamine as they affect outcomes in primary headache disorders. METHODS: We audited our use of dihydroergotamine for inpatient management of disabling primary headache, focusing on the commonly treated problems. RESULTS: Of patients interviewed, 114 had chronic migraine, 38 had cluster headache, and 11 had new daily persistent headache (NDPH). The mean time to follow-up for the entire cohort was 11 months. The data suggest that IV dihydroergotamine given over 5 days produces improvement in headache and disability in patients with migraine more than shorter courses. It does so with a cumulative effect after discharge up to a month. Giving more dihydroergotamine predicts a greater pain-free rate. Patients with cluster headache benefit from IV dihydroergotamine. In patients with NDPH, only those with migrainous symptoms responded and in that group the response was less robust compared with that seen in the chronic migraine cohort. CONCLUSIONS: Intravenous dihydroergotamine is well-tolerated, and longer treatments produce a better outcome. Nausea is the most common adverse effect, and its control is associated with a better outcome. PMID- 22049204 TI - Warfarin-related intraventricular hemorrhage: imaging and outcome. AB - OBJECTIVE: Oral anticoagulation therapy (OAT) with warfarin increases mortality and disability after intracerebral hemorrhage (ICH), the result of increased ICH volume and risk of hematoma expansion. We investigated whether OAT also influences risk of development of intraventricular hemorrhage (IVH), the volume of IVH and IVH expansion, and whether IVH is a substantive mediator of the overall effect of OAT on ICH outcome. METHODS: We performed a retrospective analysis of a prospectively collected single-center cohort of 1,879 consecutive ICH cases (796 lobar, 865 deep, 153 cerebellar, 15 multiple location, 50 primary IVH) from 1999 to 2009. ICH and IVH volumes at presentation, as well as hematoma expansion (>33% or >6 mL increase) and IVH expansion (>2 mL increase), were determined using established semiautomated methods. Outcome was assessed at 90 days using either the modified Rankin Scale or Glasgow Outcome Scale. RESULTS: Warfarin use was associated with IVH risk, IVH volume at presentation, and IVH expansion in both lobar and deep ICH (all p < 0.05) in a dose-response relationship with international normalized ratio. Warfarin was associated with poor outcome in both lobar and deep ICH (p < 0.01), and >95% of this effect was accounted for by baseline ICH and IVH volumes, as well as ICH and IVH expansion. CONCLUSION: Warfarin increases IVH volume and risk of IVH expansion in lobar and deep ICH. These findings (along with effects on ICH volume and expansion) likely represent the mechanisms by which anticoagulation worsens ICH functional outcome. PMID- 22049205 TI - Incidence and mortality of aneurysmal subarachnoid hemorrhage in two Norwegian cohorts, 1984-2007. AB - OBJECTIVE: The incidence of aneurysmal subarachnoid hemorrhage (aSAH) ranges from 4 to 10 per 100,000 person-years in most countries, and 30-day case fatality is high. The aim of this study was to estimate the incidence and case fatality of aSAH and to assess preictal predictors of survival in 2 large Norwegian population-based cohort studies. METHODS: A total of 94,976 adults (>=20 years) in the Nord-Trondelag Health Study and 31,753 participants (aged >=20 years) in the Tromso Study were included. During follow-up, aSAHs were identified, incidence rates were estimated, and predictors of survival were assessed using Cox and Poisson regression analysis. RESULTS: A total of 214 patients with aSAH were identified during 2,077,927 person-years of follow-up from 1984 to 2007. The incidence rate was 10.3 per 100,000 person-years: 13.3 for women and 7.1 for men. The incidence increased by 2% (95% confidence interval [CI] 0-4) per 5-year time period. Case fatality at 3, 7, and 30 days was 20%, 24%, and 36%. Thirty-day case fatality remained stable during follow-up (odds ratio 1.01, 95% CI 0.97-1.06 per year). Never smokers had poorer survival after aSAH than current and former smokers combined (hazard ratio 1.6, 95% CI 0.9-2.9). CONCLUSIONS: The slight increase in incidence of aSAH over time may be explained by differences in diagnostic procedures. Case fatality remained stable during 23 years of follow up. PMID- 22049206 TI - Kinase activation of ClC-3 accelerates cytoplasmic condensation during mitotic cell rounding. AB - "Mitotic cell rounding" describes the rounding of mammalian cells before dividing into two daughter cells. This shape change requires coordinated cytoskeletal contraction and changes in osmotic pressure. While considerable research has been devoted to understanding mechanisms underlying cytoskeletal contraction, little is known about how osmotic gradients are involved in cell division. Here we describe cytoplasmic condensation preceding cell division, termed "premitotic condensation" (PMC), which involves cells extruding osmotically active Cl(-) via ClC-3, a voltage-gated channel/transporter. This leads to a decrease in cytoplasmic volume during mitotic cell rounding and cell division. Using a combination of time-lapse microscopy and biophysical measurements, we demonstrate that PMC involves the activation of ClC-3 by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in human glioma cells. Knockdown of endogenous ClC-3 protein expression eliminated CaMKII-dependent Cl(-) currents in dividing cells and impeded PMC. Thus, kinase-dependent changes in Cl(-) conductance contribute to an outward osmotic pressure in dividing cells, which facilitates cytoplasmic condensation preceding cell division. PMID- 22049207 TI - This, too, shall pass--like a kidney stone: a possible path to prophylaxis of nephrolithiasis? Focus on "Cholinergic signaling inhibits oxalate transport by human intestinal T84 cells". PMID- 22049208 TI - The Na+-K+-ATPase as self-adhesion molecule and hormone receptor. AB - Thanks to the homeostasis of the internal milieu, metazoan cells can enormously simplify their housekeeping efforts and engage instead in differentiation and multiple forms of organization (tissues, organs, systems) that enable them to produce an astonishing diversity of mammals. The stability of the internal milieu despite drastic variations of the external environment (air, fresh or seawater, gastrointestinal fluids, glomerular filtrate, bile) is due to transporting epithelia that can adjust their specific permeability to H(2)O, H(+), Na(+), K(+), Ca(2+), and Cl(-) over several orders of magnitude and exchange substances with the outer milieu with exquisite precision. This exchange is due to the polarized expression of membrane proteins, among them Na(+)-K(+)-ATPase, an oligomeric enzyme that uses chemical energy from ATP molecules to translocate ions across the plasma membrane of epithelial cells. Na(+)-K(+)-ATPase presents two types of asymmetries: the arrangement of its subunits, and its expression in one pole of the epithelial cell ("polarity"). In most epithelia, polarity consists of the expression of Na(+)-K(+)-ATPase towards the intercellular space and arises in part from the interaction of the extracellular segment of the beta subunit with another beta-subunit present in a Na(+)-K(+)-ATPase molecule expressed by a neighboring cell. In addition to enabling the Na(+)-K(+)-ATPase to transport ions and water vectorially, this position exposes its receptors to ouabain and analogous cardiotonic steroids, which are present in the internal milieu because these were secreted by endocrine cells. PMID- 22049209 TI - Ischemia-induced stimulation of cerebral microvascular endothelial cell Na-K-Cl cotransport involves p38 and JNK MAP kinases. AB - Previous studies have provided evidence that, in the early hours of ischemic stroke, a luminal membrane blood-brain barrier (BBB) Na-K-Cl cotransporter (NKCC) participates in ischemia-induced cerebral edema formation. Inhibition of BBB NKCC activity by intravenous bumetanide significantly reduces edema and infarct in the rat permanent middle cerebral artery occlusion model of ischemic stroke. We demonstrated previously that the BBB cotransporter is stimulated by hypoxia, aglycemia, and AVP, factors present during cerebral ischemia. However, the underlying mechanisms have not been known. Ischemic conditions have been shown to activate p38 and JNK MAP kinases (MAPKs) in brain, and the p38 and JNK inhibitors SB-239063 and SP-600125, respectively, have been found to reduce brain damage following middle cerebral artery occlusion and subarachnoid hemorrhage, respectively. The present study was conducted to determine whether one or both of these MAPKs participates in ischemic factor stimulation of BBB NKCC activity. Cultured cerebral microvascular endothelial cell NKCC activity was evaluated as bumetanide-sensitive (86)Rb influx. Activities of p38 and JNK were assessed by Western blot and immunofluorescence methods using antibodies that detect total vs. phosphorylated (activated) p38 or JNK. We report that p38 and JNK are present in cultured cerebral microvascular endothelial cells and in BBB endothelial cells in situ and that hypoxia (7% O(2) and 2% O(2)), aglycemia, AVP, and O(2)-glucose deprivation (5- to 120-min exposures) all rapidly activate p38 and JNK in the cells. We also provide evidence that SB-239063 and SP-600125 reduce or abolish ischemic factor stimulation of BBB NKCC activity. These findings support the hypothesis that ischemic factor stimulation of the BBB NKCC involves activation of p38 and JNK MAPKs. PMID- 22049210 TI - T-type Ca2+ channels in mouse embryonic stem cells: modulation during cell cycle and contribution to self-renewal. AB - Ion channels participate in cell homeostasis and are involved in the regulation of proliferation and differentiation in several cell types; however, their presence and function in embryonic stem (ES) cells are poorly studied. We have investigated the existence of voltage-dependent inward currents in mouse ES cells and their ability to modulate proliferation and self-renewal. Patch-clamped ES cells had inactivating tetrodotoxin (TTX)-sensitive Na(+) currents as well as transient Ca(2+) currents abolished by the external application of Ni(2+). Biophysical and pharmacological data indicated that the Ca(2+) current is predominantly mediated by T-type (Ca(v)3.2) channels. The number of cells expressing T-type channels and Ca(v)3.2 mRNA levels increased at the G1/S transition of the cell cycle. TTX had no effect on ES cell proliferation. However, blockade of T-type Ca(2+) currents with Ni(2+) induced a decrease in proliferation and alkaline phosphatase positive colonies as well as reduced expression of Oct3/4 and Nanog, all indicative of loss in self-renewal capacity. Decreased alkaline phosphatase and Oct3/4 expression were also observed in cells subjected to small interfering RNA-induced knockdown for T-type (Ca(v)3.2) Ca(2+) channels, thus partially recapitulating the pharmacological effects on self renewal. These results indicate that Ca(v)3.2 channel expression in ES cells is modulated along the cell cycle being induced at late G1 phase. They also suggest that these channels are involved in the maintenance of the undifferentiated state of mouse ES cells. We propose that Ca(2+) entry mediated by Ca(v)3.2 channels might be one of the intracellular signals that participate in the complex network responsible for ES cell self-renewal. PMID- 22049211 TI - Calsequestrin (CASQ1) rescues function and structure of calcium release units in skeletal muscles of CASQ1-null mice. AB - Amplitude of Ca(2+) transients, ultrastructure of Ca(2+) release units, and molecular composition of sarcoplasmic reticulum (SR) are altered in fast-twitch skeletal muscles of calsequestrin-1 (CASQ1)-null mice. To determine whether such changes are directly caused by CASQ1 ablation or are instead the result of adaptive mechanisms, here we assessed ability of CASQ1 in rescuing the null phenotype. In vivo reintroduction of CASQ1 was carried out by cDNA electro transfer in flexor digitorum brevis muscle of the mouse. Exogenous CASQ1 was found to be correctly targeted to the junctional SR (jSR), as judged by immunofluorescence and confocal microscopy; terminal cisternae (TC) lumen was filled with electron dense material and its width was significantly increased, as judged by electron microscopy; peak amplitude of Ca(2+) transients was significantly increased compared with null muscle fibers transfected only with green fluorescent protein (control); and finally, transfected fibers were able to sustain cytosolic Ca(2+) concentration during prolonged tetanic stimulation. Only the expression of TC proteins, such as calsequestrin 2, sarcalumenin, and triadin, was not rescued as judged by Western blot. Thus our results support the view that CASQ1 plays a key role in both Ca(2+) homeostasis and TC structure. PMID- 22049212 TI - Integrin alpha6beta4 cooperates with LPA signaling to stimulate Rac through AKAP Lbc-mediated RhoA activation. AB - The alpha(6)beta(4) integrin promotes carcinoma invasion through its ability to promote directed migration and polarization of carcinoma cells. In this study, we explore how the alpha(6)beta(4) integrin cooperates with lysophosphatidic acid (LPA) to activate Rho and Rac small GTPases. Through the use of dominant negative Rho constructs, C3 exotransferase, and Rho kinase inhibitor, we find that Rho is critical for LPA-dependent chemotaxis and lamellae formation. However, utilization of specific Rho isoforms depends on integrin alpha(6)beta(4) expression status. Integrin alpha(6)beta(4)-negative MDA-MB-435 cells utilize only RhoC for motility, whereas integrin alpha(6)beta(4)-expressing cells utilize RhoC but additionally activate and utilize RhoA for LPA-dependent cell motility and lamellae formation. Notably, the activation of RhoA by cooperative LPA and integrin alpha(6)beta(4) signaling requires the Rho guanine nucleotide exchange factor AKAP-Lbc. We also determine that integrin alpha(6)beta(4) cannot activate Rac1 directly but promotes LPA-mediated Rac1 activation that is dependent on RhoA activity and de novo beta(1) integrin ligation. Finally, we find that the regulation of Rac1 and RhoA in response to LPA is differentially regulated by phosphodiesterases, PKA, and phosphatidylinositol 3-kinase, thus supporting their spatially distinct compartmentalization. In summary, signaling from integrin alpha(6)beta(4) facilitates LPA-stimulated chemotaxis through preferential activation of RhoA, which, in turn, facilitates activation of Rac1. PMID- 22049213 TI - Functional role of NHE4 as a pH regulator in rat and human colonic crypts. AB - To regulate ionic and fluid homeostasis, the colon relies upon a series of Na(+) dependent transport proteins. Recent studies have identified a sodium/hydrogen exchanger (NHE) 4 (NHE4) protein in the gastrointestinal tract but to date there has been little description of its function. Additionally, we have previously shown that aldosterone can rapidly modulate Na(+)-dependent proton excretion via NHE proteins. In this study we examined the role of NHE4 in rat and human colonic crypts, determined the effect of aldosterone on NHE4 specifically, and explored the intracellular pathways leading to activation. Colonic samples were dissected from Sprague-Dawley rats. Human specimens were obtained from patients undergoing elective colon resections. Crypts were isolated using ethylenediaminetetraacetic acid and intracellular pH (pH(i)) changes were monitored using 2'-7' bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Crypts were exposed to 7 MUM ethylisopropylamiloride or 400 MUM amiloride, doses previously shown to inhibit NHE1 and NHE3 but allow NHE4 to remain active. Functional NHE4 activity was demonstrated in both rat and human colonic crypts. NHE4 activity was increased in the presence of 1 MUM aldosterone. In the rat model, crypts were exposed to 100 MUM 3-isobutyl-1-methylxanthine/1 MUM forskolin and demonstrated a decrease in NHE4 activity with increased cAMP levels. No significant change in NHE4 activity was seen by increasing osmolarity. These results demonstrate functional NHE4 activity in the rat and human colon and an increase in activity by aldosterone. This novel exchanger is capable of modulating intracellular pH over a wide pH spectrum and may play an important role in maintaining cellular pH homeostasis. PMID- 22049214 TI - Toll-like receptor deficiency worsens inflammation and lymphedema after lymphatic injury. AB - Mechanisms regulating lymphedema pathogenesis remain unknown. Recently, we have shown that lymphatic fluid stasis increases endogenous danger signal expression, and these molecules influence lymphatic repair (Zampbell JC, et al. Am J Physiol Cell Physiol 300: C1107-C1121, 2011). Endogenous danger signals activate Toll like receptors (TLR) 2, 4, and 9 and induce homeostatic or harmful responses, depending on physiological context. The purpose of this study was to determine the role of TLRs in regulating tissue responses to lymphatic fluid stasis. A surgical model of lymphedema was used in which wild-type or TLR2, 4, or 9 knockout (KO) mice underwent tail lymphatic excision. Six weeks postoperatively, TLR KOs demonstrated markedly increased tail edema compared with wild-type animals (50-200% increase; P < 0.01), and this effect was most pronounced in TLR4 KOs (P < 0.01). TLR deficiency resulted in decreased interstitial and lymphatic transport, abnormal lymphatic architecture, and fewer capillary lymphatics (40 50% decrease; P < 0.001). Lymphedematous tissues of TLR KOs demonstrated increased leukocyte infiltration (P < 0.001 for TLR4 KOs), including higher numbers of infiltrating CD3+ cells (P < 0.05, TLR4 and TLR9 KO), yet decreased infiltrating F4/80+ macrophages (P < 0.05, all groups). Furthermore, analysis of isolated macrophages revealed twofold reductions in VEGF-C (P < 0.01) and LYVE-1 (P < 0.05) mRNA from TLR2-deficient animals. Finally, TLR deficiency was associated with increased collagen type I deposition and increased transforming growth factor-beta1 expression (P < 0.01, TLR4 and TLR9 KO), contributing to dermal fibrosis. In conclusion, TLR deficiency worsens tissue responses to lymphatic fluid stasis and is associated with decreased lymphangiogenesis, increased fibrosis, and reduced macrophage infiltration. These findings suggest a role for innate immune responses, including TLR signaling, in lymphatic repair and lymphedema pathogenesis. PMID- 22049215 TI - Ligand-induced internalization of the type 1 cholecystokinin receptor independent of recognized signaling activity. AB - Receptor ligands, identified as antagonists, based on the absence of stimulation of signaling, can rarely stimulate receptor internalization. d-Tyr-Gly [(Nle(28,31),d-Trp(30))CCK-26-32]-2-phenylethyl ester (d-Trp-OPE) is such a ligand that binds to the cholecystokinin (CCK) receptor and stimulates internalization. Here, the molecular basis of this trafficking event is explored, with the assumption that ligand binding initiates conformational change, exposing an epitope to direct endocytosis. Ligand-stimulated internalization was studied morphologically using fluorescent CCK and d-Trp-OPE. d-Trp-OPE occupation of Chinese hamster ovary cell receptors stimulated internalization into the same region as CCK. Arrestin-biased action was ruled out using morphological translocation of fluorescent arrestin 2 and arrestin 3, moving to the membrane in response to CCK, but not d-Trp-OPE. Possible roles of the carboxyl terminus were studied using truncated receptor constructs, eliminating the proline-rich distal tail, the serine/threonine-rich midregion, and the remainder to the vicinal cysteines. None of these constructs disrupted d-Trp-OPE-stimulated internalization. Possible contributions of transmembrane segments were studied using competitive inhibition with peptides that also had no effect. Intracellular regions were studied with a similar strategy using coexpressing cell lines. Peptides corresponding to ends of each loop region were studied, with only the peptide at the carboxyl end of the third loop inhibiting d-Trp-OPE-stimulated internalization but having no effect on CCK-stimulated internalization. The region contributing to this effect was refined to peptide 309-323, located below the recognized G protein-association motif. While a receptor in which this segment was deleted did internalize in response to d-Trp-OPE, it exhibited abnormal ligand binding and did not signal in response to CCK, suggesting an abnormal conformation and possible mechanism of internalization distinct from that being studied. This interpretation was further supported by the inability of peptide 309-323 to inhibit its d-Trp-OPE-stimulated internalization. Thus the 309 323 region of the type 1 CCK receptor affects antagonist-stimulated internalization of this receptor, although its mechanism and interacting partner are not yet clear. PMID- 22049216 TI - Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. AB - AIM: To define a predictive model for clinical behaviour of breast phyllodes tumours (PT) using histological parameters and surgical margin status. METHODS: Cases of breast PT diagnosed in the Department of Pathology Singapore General Hospital between January 1992 and December 2010 were stratified into benign, borderline and malignant grades based on a combination of histological parameters (stromal atypia, hypercellularity, mitoses, overgrowth and nature of tumour borders). Surgical margin status was assessed. Clinical follow-up and biostatistical modelling were accomplished. RESULTS: Of 605 PT, 440 (72.7%) were benign, 111 (18.4%) borderline and 54 (8.9%) malignant. Recurrences, which were predominantly local, were documented in 80 (13.2%) women. Deaths from PT occurred in 12 (2%) women. Multivariate analysis revealed stromal atypia, overgrowth and surgical margins to be independently predictive of clinical behaviour, with mitoses achieving near significance. Stromal hypercellularity and tumour borders were not independently useful. A nomogram developed based on atypia, mitoses, overgrowth and surgical margins (AMOS criteria) could predict recurrence-free survival at 1, 3, 5 and 10 years. This nomogram was superior to a total histological score derived from adding values assigned to each of five histological parameters. CONCLUSION: A predictive nomogram based on three histological criteria and surgical margin status can be used to calculate recurrence-free survival of an individual woman diagnosed with PT. This can be applied for patient counselling and clinical management. PMID- 22049218 TI - A review of the clinical presentation, natural history and inheritance of variegate porphyria: its implausibility as the source of the 'Royal Malady'. AB - It has been suggested that King George III of Great Britain suffered from the haem biosynthetic disorder, variegate porphyria. This diagnosis is pervasive throughout the scientific and popular literature, and is often referred to as the 'Royal Malady.' The authors believe it inappropriate to view the case for porphyria purely in terms of symptoms, as has generally been the case in his presumptive acute porphyria diagnosis. Accordingly, this review provides a current description of the natural history and clinical presentation of the porphyrias, against which we measure the case for porphyria in George III and his relatives. The authors have critically assessed the prevalence of porphyria in a population, the expected patterns and frequency of inheritance, its penetrance and its expected natural history in affected individuals, and conclude that neither George nor his relatives had porphyria, based on four principal reasons. First, the rarity of the disease mandates a very low prior probability, and therefore implies a vanishingly low positive predictive value for any diagnostic indicator of low specificity, such as a historical reading of the symptoms. Second, penetrance of this autosomal dominant disorder is approximately 40%, and one may expect to have identified characteristic clinical features of porphyria in a large number of descendants without difficulty. Third, the symptoms of both George III and his relatives are highly atypical for porphyria and are more appropriately explained by other much commoner conditions. Finally, the natural history of the illnesses reported in this family is as atypical for variegate porphyria as are their symptoms. PMID- 22049217 TI - Antifungal treatment affects the laboratory diagnosis of invasive aspergillosis. AB - AIMS: The purpose of this study was to investigate the performance of non invasive diagnostic tests such as galactomannan enzyme immunoassay and quantitative PCR in the early diagnosis of invasive aspergillosis (IA), and how these tests are impacted upon by the use of different classes of antifungal agents in an in-vivo model of IA. METHODS: A standardised rat inhalation model of IA was used to examine the effects of an azole, posaconazole, a polyene, amphotericin B and an echinocandin caspofungin. Daily blood samples were collected for subsequent analysis using a commercially available galactomannan assay and an inhouse qPCR assay. RESULTS: No significant differences were observed in the CE/g of Aspergillus fumigatus in the lungs of each group. qPCR was statistically more sensitive than galactomannan for both the early detection of infected controls (p=0.045) and for overall detection (p=0.018). However, antifungal treatment significantly reduced the overall sensitivity of qPCR (p=0.020); these effects were due to posaconazole and caspofungin. In the latter stages of infection (days 4 and 5) there were no significant differences in the numbers of infections detected by galactomannan and qPCR; however, the antifungal class used caused significant qualitative differences (p=0.041). Galactomannan showed improved detection in posaconazole-treated animals. CONCLUSIONS: Previous exposure to antifungal therapy must be considered when interpreting either qPCR or galactomannan-based IA diagnostics as this study has shown that individual classes of antifungal agents impact upon the dynamics of antigen and DNA release into the circulation. PMID- 22049219 TI - Preanalytical mixing of whole-blood specimens in the context of the Athlete Passport. AB - BACKGROUND: Full blood counts are now used as evidence that athletes have used banned blood doping. This has led to legal scrutiny of the efficacy of preanalytical procedures such as specimen homogenisation. AIMS: To characterise the impact of different mixing strategies on whole-blood homogeneity. METHODS: Manual inversion, mechanical mixing and automatic mixing performed by the Sysmex XT-2000i were evaluated. RESULTS: Automated mixing by the instrument, or 1 min of mechanical mixing, thoroughly homogenised specimens even for tubes that had been refrigerated and left undisturbed for 36 h. Manual inversions were almost as effective, provided that specimens were first allowed to equilibrate to ambient temperatures. CONCLUSIONS: Current sport guidelines that mandate at least 15 min of mechanical mixing are excessive. Except where specimens are presented to the instrument manually, mechanical mixing is redundant in the context of full blood counts. PMID- 22049220 TI - Is breast specimen shrinkage really a problem in breast-conserving surgery? AB - BACKGROUND: Breast-conserving surgery currently focuses on improving margin clearance and excision volume, the main pathology report parameters for oncological and cosmetic outcomes. AIM: To quantitatively evaluate discrepancies in surgical and pathological estimates of breast specimen sizes, including the influence of formalin fixation. METHODS: This prospective multicentre study included 68 breast specimens of consecutive patients undergoing breast-conserving surgery for breast cancer in three affiliated hospitals between November 2010 to May 2011. Specimens were weighed immediately after excision. Specimen volumes were calculated from the length, width and height. Actual specimen volumes were measured using volume displacement. Specimens were weighed once again after arrival at the pathology department, and volumes recalculated. The smallest pre- and post-fixation distances to the tumour-free margin were compared. RESULTS: The mean surgical specimen weight was 47.7 g and was approximately similar to the actual specimen volume of 49.8 cm(3). The weights of specimens immediately following surgery and on pathological appraisal were equal (p=0.94). The calculated volumes differed significantly from the actual specimen volumes (p>0.05). The mean distance to the closest tumour-free margin, 0.35 cm, was not altered by formalin fixation (p=0.1). CONCLUSIONS: No evidence was found to suggest that surgical breast specimens shrink in the period between the surgical procedure and pathological examination, or following formalin fixation. The pathological appraisal of specimen margins and volumes is not affected by changes in specimen size. As calculations of specimen volumes are unreliable, the use of water displacement or the more readily available specimen weight is recommended for accurate volume measurement. Pathologists should be encouraged to always measure and record specimen weight. PMID- 22049221 TI - Electron microscope study on a transmissible cytotoxic factor isolated from cerebrospinal fluid of neurological patients: analysis of its structure and of its effects on various types of cell cultures. AB - AIMS: In previous studies, the present group showed that a factor, present in the cerebrospinal fluid of seven neuro-patients, was capable of inducing cell damages on cell cultures of epithelial cells (Vero), glial cells (DG54-MG) and human primary lymphocytes. The cytotoxicity, once induced, could be transmitted to fresh cell cultures using crude preparations obtained from the cytotoxic cell cultures. METHODS AND RESULTS: The present electron microscope study describes in detail the pathological changes occurring in the previously assayed cultured cell types, and for the first time in human fibroblasts, as a consequence of the treatment with crude cytotoxic preparation. It also demonstrates with reasonable certainty the absence of virus-like particles in both the treated cells and the partially purified cytotoxic fraction. Indeed high-resolution electron microscopy analysis shows that this fraction consists almost entirely of protein spheroids with a diameter of 8-12 nm. CONCLUSIONS: The possible significance of nanotubular aggregates, observed in particular in the glial and in the epithelial cells undergoing cytotoxic damage, is also discussed. PMID- 22049222 TI - Female Anderson--Fabry disease mimicking hypertrophic cardiomyopathy. PMID- 22049223 TI - Correlation between expression of cellular retinol-binding protein 1 and its methylation status in larynx cancer. AB - AIMS: The authors have previously reported that cellular retinol-binding protein 1 (CRBP1) gene gain and its expression correlated significantly with survival in laryngeal carcinoma patients. The authors hypothesised that inactivation of the CRBP1 gene through CpG methylation is associated with patient status and gene expression. In this work, the authors determine the expression and methylation status of the CRBP1 gene and its correlation with clinical variables of laryngeal carcinoma patients. METHODS: The CRBP1 gene methylation promoter was assessed by methylation specific PCR analysis in tissue samples from larynx cancer specimens and its expression was assessed by immunohistochemistry on paraffin embedded tissue using tissue microarray. The results were then compared with the clinical pathological variables and outcome measures. The study included 46 samples from patients with non-metastatic squamous cell carcinoma of the larynx without any previous oncological treatments. RESULTS: Lack of CRBP1 expression was seen in 17 of the 46 laryngeal carcinoma samples, while the remaining 29 samples showed increased expression. Significant associations were found between CRBP1 expression and methylation and patient status. There was a tendency for association in all clinical stages of the disease. CRBP1 gene expression and its unmethylated promoter correlated significantly with survival (p<0.05). CONCLUSIONS: An early event of larynx cancer could be CRBP1 expression related to unmethylation of the promoter region. These features could also be associated with good response and survival. The authors hypothesised that increased expression and unmethylated promoter of the CRBP1 gene could be considered as markers for larynx cancer. PMID- 22049224 TI - Antigens of persistent Chlamydia pneumoniae within coronary atheroma from patients undergoing heart transplantation. AB - AIMS: In order for Chlamydia pneumoniae to play a causative role in chronic human disease, it would need to persist within infected tissue for extended periods of time. Current theory suggests that C pneumoniae may persist at the site of infection via an alternative replicative form, known as an aberrant body. METHODS: A panel of C pneumoniae-specific antibodies upregulated by the aberrant body was used to probe tissue specimens from the coronary atheroma from 13 explanted hearts to identify patterns of reactivity in these tissues, as well as to determine the presence and prevalence of C pneumoniae aberrant bodies. RESULTS: Six of 13 patients had an ischaemic cardiomyopathy secondary to coronary atherosclerosis, while another six patients had an idiopathic, dilated cardiomyopathy. One additional patient, a young (24 years) woman with cardiomyopathy, had no history of atherosclerotic disease. Eleven patients were positive by immunohistochemistry with at least one antibody. Coronary arteries of the two other patients were negative by immunohistochemistry with all antibodies. One of these patients was the 24-year-old woman with grade I disease and no risk factors for coronary artery disease. CONCLUSIONS: The protein antigens of persistent C pneumoniae infection found in the atheromatous lesions from patients in this study could potentially be used as markers to detect such infections and some may be virulence factors or immunogens specific to C pneumoniae, thus serving as target molecules for diagnostic use or therapeutic intervention. PMID- 22049225 TI - Tumour-infiltrating macrophages and clinical outcome in breast cancer. AB - BACKGROUND: Macrophages constitute a major component of the leucocytic infiltrate of tumours. Human studies show an association between tumour-associated macrophages and tumours with poor prognostic features. In breast cancer, the presence of macrophages has been correlated with increased angiogenesis and poor prognosis but little information is available about the independent prognostic role of macrophages infiltrating breast carcinomas. AIMS AND METHODS: This study used immunohistochemistry and tissue microarrays to assess the density and localisation of CD68 macrophages infiltrating 1322 breast tumours and to identify any relationship with clinicopathological factors and patient outcome. RESULTS: Tumour-infiltrating macrophages were present in the majority of tumours with a predominantly diffuse pattern. The density of distant stromal macrophages (infiltrating stroma away from the carcinoma, median count 14 cells) was higher than intratumoural (median zero cells) and adjacent stromal macrophages (median three cells). Higher total macrophage number was associated with higher tumour grade (r(s)=0.39, p<0.001), ER and PgR negativity, HER-2 positivity and basal phenotype (p<0.001). In univariate survival analysis, higher numbers of CD68 macrophages were significantly associated with worse breast cancer-specific survival (p<0.001) and shorter disease-free interval (p=0.004). However in multivariate model analysis, the CD68 macrophage count was not an independent prognostic marker. CONCLUSIONS: Macrophages are heterogeneous with different subsets having different functions. The present study suggests that overall macrophage numbers are not related to prognosis in breast cancer. However, further studies are needed to investigate the potential role of different subsets of macrophages. PMID- 22049226 TI - Receptor activator for nuclear factor kappa B expression predicts poor prognosis in breast cancer patients with bone metastasis but not in patients with visceral metastasis. AB - BACKGROUND: It was recently reported that receptor activator for nuclear factor kappa B ligand (RANKL)/receptor activator for nuclear factor kappa B (RANK) pathway is critical for RANK-expressing cancer cells to home to bone and associates with disease progression of cancer. The present study was aimed to evaluate the effect of RANK on prognosis in breast cancer patients with bone metastasis and patients with visceral metastasis. METHODS: Immunohistochemical staining for RANK was carried out on paraffin-embedded primary tumour tissue sections from 102 patients with metastatic breast cancer. Survival analysis and Cox proportional hazards model were used to explore the prognostic value of RANK expression in breast cancer. RESULTS: The RANK expression rates were 47.1% in metastatic breast cancer. Patients with RANK expression showed significantly poor progression-free survival and disease-specific survival. Subgroup analysis demonstrated that the significant difference in prognosis completely resulted from the occurrence of bone metastasis. Multivariate analysis demonstrated that RANK expression was an independent predictor of bone metastasis-free survival and disease-specific survival in patients with bone metastasis. CONCLUSIONS: RANK expression might be an independent predictor of poor prognosis in breast cancer patients with bone metastasis, and RANK expression does not associate with the prognosis in patients with visceral metastasis. PMID- 22049227 TI - Serglycin: a structural and functional chameleon with wide impact on immune cells. AB - Among the different proteoglycans expressed by mammals, serglycin is in most immune cells the dominating species. A unique property of serglycin is its ability to adopt highly divergent structures, because of glycosylation with variable types of glycosaminoglycans when expressed by different cell types. Recent studies of serglycin-deficient animals have revealed crucial functions for serglycin in a diverse array of immunological processes. However, its exact function varies to a large extent depending on the cellular context of serglycin expression. Based on these findings, serglycin is emerging as a structural and functional chameleon, with radically different properties depending on its exact cellular and immunological context. PMID- 22049228 TI - R-alpha-lipoic acid does not reverse hepatic inflammation of aging, but lowers lipid anabolism, while accentuating circadian rhythm transcript profiles. AB - To determine the effects of age and lipoic acid supplementation on hepatic gene expression, we fed young (3 mo) and old (24 mo) male Fischer 344 rats a diet with or without 0.2% (wt/wt) R-alpha-lipoic acid (LA) for 2 wk. Total RNA isolated from liver tissue was analyzed by Affymetrix microarray to examine changes in transcriptional profiles. Results showed elevated proinflammatory gene expression in the aging liver and evidence for increased immune cell activation and tissue remodeling, together representing 45% of the age-related transcriptome changes. In addition, age-related increases in transcripts of genes related to fatty acid, triglyceride, and cholesterol synthesis, including acetyl-CoA carboxylase-beta (Acacb) and fatty acid synthase (Fasn), were observed. Supplementation of old animals with LA did not reverse the necroinflammatory phenotype but, intriguingly, altered the expression of genes governing circadian rhythm. Most notably, Arntl, Npas2, and Per changed in a coordinated manner with respect to rhythmic transcription. LA further caused a decrease in transcripts of several bile acid and lipid synthesis genes, including Acacb and Fasn, which are regulated by first-order clock transcription factors. Similar effects of LA supplementation on bile acid and lipid synthesis genes were observed in young animals. Transcript changes of lipid metabolism genes were corroborated by a decrease in FASN and ACC protein levels. We conclude that advanced age is associated with a necroinflammatory phenotype and increased lipid synthesis, while chronic LA supplementation influences hepatic genes associated with lipid and energy metabolism and circadian rhythm, regardless of age. PMID- 22049229 TI - Divergent mechanism regulating fluid intake and metabolism by the brain renin angiotensin system. AB - The purpose of this review is two-fold. First, I will highlight recent advances in our understanding of the mechanisms regulating angiotensin II (ANG II) synthesis in the brain, focusing on evidence that renin is expressed in the brain and is expressed in two forms: a secreted form, which may catalyze extracellular ANG I generation from glial or neuronal angiotensinogen (AGT), and an intracellular form, which may generate intracellular ANG in neurons that may act as a neurotransmitter. Second, I will discuss recent studies that advance the concept that the renin-angiotensin system (RAS) in the brain not only is a potent regulator of blood pressure and fluid intake but may also regulate metabolism. The efferent pathways regulating the blood pressure/dipsogenic effects and the metabolic effects of elevated central RAS activity appear different, with the former being dependent upon the hypothalamic-pituitary-adrenal axis, and the latter being dependent upon an interaction between the brain and the systemic (or adipose) RAS. PMID- 22049230 TI - Acid secretion by mitochondrion-rich cells of medaka (Oryzias latipes) acclimated to acidic freshwater. AB - In the present study, medaka embryos were exposed to acidified freshwater (pH 5) to investigate the mechanism of acid secretion by mitochondrion-rich (MR) cells in embryonic skin. With double or triple in situ hybridization/immunocytochemistry, the Na(+)/H(+) exchanger 3 (NHE3) and H(+) ATPase were localized in two distinct subtypes of MR cells. NHE3 was expressed in apical membranes of a major proportion of MR cells, whereas H(+)-ATPase was expressed in basolateral membranes of a much smaller proportion of MR cells. Gill mRNA levels of NHE3 and H(+)-ATPase and the two subtypes of MR cells in yolk sac skin were increased by acid acclimation; however, the mRNA level of NHE3 was remarkably higher than that of H(+)-ATPase. A scanning ion-selective electrode technique was used to measure H(+), Na(+), and NH(4)(+) transport by individual MR cells in larval skin. Results showed that Na(+) uptake and NH(4)(+) excretion by MR cells increased after acid acclimation. These findings suggested that the NHE3/Rh glycoprotein-mediated Na(+) uptake/NH(4)(+) excretion mechanism plays a critical role in acidic equivalent (H(+)/NH(4)(+)) excretion by MR cells of the freshwater medaka. PMID- 22049231 TI - Oxidative stress contributes to sex differences in angiotensin II-mediated hypertension in spontaneously hypertensive rats. AB - NADPH oxidase has been implicated in ANG II-induced oxidative stress and hypertension in males; however, the contribution of oxidative stress to ANG II hypertension in females is unknown. In the present study, we tested the hypothesis that greater antioxidant capacity in female spontaneously hypertensive rats (SHR) blunts ANG II-induced oxidative stress and hypertension relative to males. Whole body and renal cortical oxidative stress levels were assessed in female and male SHR left untreated or following 2 wk of chronic ANG II infusion. Chronic ANG II infusion increased NADPH oxidase enzymatic activity in the renal cortex of both sexes; however, this increase only reached significance in female SHR. In contrast, male SHR demonstrated a greater increase in all measurements of reactive oxygen species production in response to chronic ANG II infusion. ANG II infusion increased plasma superoxide dismutase activity only in female SHR (76 +/ 9 vs. 190 +/- 7 Units.ml(-1).mg(-1), P < 0.05); however, cortical antioxidant capacity was unchanged by ANG II in either sex. To assess the functional implication of alterations in NADPH enzymatic activity and oxidative stress levels following ANG II infusion, additional experiments assessed the ability of the in vivo antioxidant apocynin to modulate ANG II hypertension. Apocynin significantly blunted ANG II hypertension in male SHR (174 +/- 2 vs. 151 +/- 1 mmHg, P < 0.05), with no effect in females (160 +/- 11 vs. 163 +/- 10 mmHg). These data suggest that ANG II hypertension in male SHR is more dependent on increases in oxidative stress than in female SHR. PMID- 22049232 TI - Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats. AB - We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker (fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser(473) phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the strategy of targeting the RAS to improve both blood pressure regulation and insulin action in conditions of insulin resistance. PMID- 22049234 TI - Eating your words: discursive psychology and the reconstruction of eating practices. AB - Psychological research into eating practices has focused mainly on attitudes and behaviour towards food, and disorders of eating. Using experimental and questionnaire-based designs, these studies place an emphasis on individual consumption and cognitive appraisal, overlooking the interactive context in which food is eaten. The current article examines eating practices in a more naturalistic environment, using mealtime conversations tape-recorded by families at home. The empirical data highlight three issues concerning the discursive construction of eating practices, which raise problems for the existing methodologies. These are: (1) how the nature and evaluation of food are negotiable qualities; (2) the use of participants' physiological states as rhetorical devices; and (3) the variable construction of norms of eating practices. The article thus challenges some key assumptions in the dominant literature and indicates the virtues of an approach to eating practices using interactionally based methodologies. PMID- 22049233 TI - Blood pressure regulation in diabetic patients with and without peripheral neuropathy. AB - Cardiac and vascular dysfunctions resulting from autonomic neuropathy (AN) are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure (BP) regulation in patients with peripheral neuropathy and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. We continuously measured electrocardiogram, arterial BP, and respiration during supine rest and 70 degrees head-up tilt in 12 able-bodied subjects, 7 diabetics without, 7 diabetics with possible, and 8 diabetics with definite, sensory, and/or motor neuropathy (D2). During the first 3 min of tilt, systolic BP (SBP) of D2 decreased [-10.9 +/- 4.5 (SE) mmHg] but increased in able-bodied (+4.8 +/- 5.4 mmHg). Compared with able-bodied, D2 had smaller low-frequency (0.04-0.15 Hz) spectral power of diastolic BP, lower baroreflex effectiveness index (BEI), and more SBP ramps. Except for low-frequency power of SBP, D2 had greater SBP and smaller RR interval harmonic and nonharmonic components at rest across the 0.003- to 0.45-Hz region. In addition, our results support previous findings of smaller HF RR interval power, smaller numbers of baroreflex sequences, and lower baroreflex sensitivity in D2. We conclude that diabetic peripheral neuropathy is accompanied by diminished parasympathetic and sympathetic control of heart rate and peripheral vasomotion and diminished baroreflex regulation. A novel finding of this study lies in the sensitivity of BEI to detect AN, presumably because of its combination of parameters that measure reductions in both sympathetic control of vasomotion and parasympathetic control of heart rate. PMID- 22049235 TI - Parental Non-verbal Sexual Communication: Its Relationship to Sexual Behaviour and Sexual Guilt. AB - The study explores the link between remembered non-verbal sexual communication in the home, current sexual behaviours and feelings of sexual guilt, among a sample of young British men and women. Non-verbal sexual communication encapsulates: openness about nudity in the home; the showing of affection between parents; signs of parental sexual activity and contraceptive use; and intimation of mother's menstruation. One hundred and thirty-seven young adults completed questionnaires measuring remembered parental non-verbal sexual communication, current sexual behaviour and sexual guilt. Higher levels of parental non-verbal sexual communication were found to be linked to: earlier onset of sexual activity, fewer sexual partners and lower feelings of aspects of sexual guilt. The findings are discussed in terms of how to advance this area of study. PMID- 22049236 TI - Longitudinal Influences of Knowledge and Self-efficacy on Exercise Behavior: Tests of a Mutual Reinforcement Model. AB - The central tenet of social cognitive theory, that individuals' construal processes and behaviors mutually reinforce each other, is tested for exercise behavior. Two longitudinal data sets (year 1 to year 2 and year 1 to year 6) from the Stanford Five-City Project, a field experiment to promote cardiovascular disease prevention in California, are analyzed through structural equation modeling techniques to evaluate the effects of demographics, exercise knowledge, and exercise self-efficacy on exercise behavior. The effects of exercise behavior on subsequent knowledge and self-efficacy are also examined. In both data sets (year 1 to year 2, N = 1254 and year 1 to year 6, N = 939), education, income, age, and sex were significant predictors of exercise behavior. Self-efficacy and knowledge also predicted behavior. Prior exercise behavior predicted subsequent knowledge and self-efficacy. Prior knowledge and self-efficacy, in turn, predicted subsequent exercise behavior. Recommendations are made for enhancing the effectiveness of public health efforts designed to promote healthy behaviors. PMID- 22049237 TI - Responses to Information about Psychosocial Consequences of Genetic Testing for Breast Cancer Susceptibility: Influences of Cancer Worry and Risk Perceptions. AB - We assessed the impact of information about psychosocial consequences of genetic testing for breast cancer susceptibility on interest in and beliefs about genetic testing, and whether these effects vary by levels of either cancer worry or perceived cancer risk. Women (N = 180) in an experimental study were randomly assigned to read one of four messages consisting of standard information along with information about either psychosocial advantages, potential disadvantages, both advantages and disadvantages, or no additional information. Women receiving only standard information reported higher interest in obtaining genetic testing than did women who received additional information about advantages, disadvantages, or both advantages and disadvantages. Cancer worry (but not perceived risk) predicted greater interest and more favorable beliefs about the benefits of testing. Beliefs that testing causes emotional distress were positively associated with worry and negatively associated with risk perceptions. PMID- 22049238 TI - Attitudes regarding chronic fatigue syndrome: the importance of a name. AB - Undergraduates from diverse academic backgrounds and medical trainees were assessed regarding their attitudes about and familiarity with chronic fatigue syndrome (CFS). We explored whether different names given to chronic fatigue syndrome (CFS, myalgic encephalopathy, or Florence Nightingale disease) were associated with differences in attributions regarding its cause, nature, severity, contagion, prognosis, and treatment. Participants' attributions toward the illness varied with the names used to characterize it. Participants prompted with the myalgic encephalopathy name were more likely to attribute a biomedical cause to the illness, and less likely to consider patients as candidates for organ donation than those prompted with the CFS name. Although the medical trainees were less likely to consider the patient as malingering, and more likely to view the illness as leading to poorer quality of life and a poorer prognosis, they were also more likely to consider the illness a form of primary depression, more likely to think the patient would attempt suicide, and less likely to consider associated cognitive symptoms as severe. The implications are discussed. PMID- 22049239 TI - Workplace bullying in nurses. AB - The article reports a study of workplace bullying in community nurses in an NHS trust. The aims were to determine the prevalence of bullying, to examine the association between bullying and occupational health outcomes, and to investigate whether support at work could moderate the effects of bullying. Forty-four percent of nurses reported experiencing one or more types of bullying in the previous 12 months, compared to 35 percent of other staff. Fifty percent of nurses had witnessed the bullying of others. Nurses who had been bullied reported significantly lower levels of job satisfaction and significantly higher levels of anxiety, depression and propensity to leave. They were also more critical of aspects of the organizational climate of the trust. Support at work was able to protect nurses from some of the damaging effects of bullying. PMID- 22049240 TI - Adjustment to an artificial limb: a qualitative perspective. AB - The purpose of this study was to identify factors considered to be important in the adjustment to amputation and the wearing of a prosthetic limb from the perspective of the person who has had a lower limb amputation. Hence, focus group methodology was employed as a means of acquiring perspectives within a population of young adults who had a lower limb amputation. Preliminary thematic analysis revealed that factors such as self-image, social, physical and practical concerns, the meaning attributed to and the acceptance of the amputation and support among others were important in the adjustment process. These findings have substantial implications for directing future research. PMID- 22049241 TI - Correlates and Predictors of Self-reported Psychological and Physical Morbidity in Chronic Caregiver Stress. AB - An investigation was conducted to explore: (1) whether psychological and physical morbidity share similar psychosocial determinants; (2) the long-term stability of these determinants; and (3) the role of neuroticism in predicting psychological and physical morbidity. Fifty spousal caregivers of dementia patients were recruited into a 12-month study. Participants were followed up at six-monthly interva ls during which they completed scales measuring psychosocial mediators, psychological morbidity, physical morbidity and neuroticism. Psychological morbidity was influenced primarily by indices of coping and neuroticism. Physical morbidity was influenced primarily by indices of psychological morbidity (increased psychological morbidity was associated with perceptions of greater physical morbidity). Neuroticism exhibited significant cross-sectional and longitudinal relationships with the indices of psychological morbidity, but only cross-sectional relationships with the indices of physical morbidity. PMID- 22049242 TI - Commentary on Siegel and Schrimshaw's 'Coping with negative emotions: The cognitive strategies of HIV-infected gay/bisexual men'. PMID- 22049243 TI - Coping with negative emotions: a reply to somerfield and fogarty. PMID- 22049244 TI - Lipid droplets as fat storage organelles in Caenorhabditis elegans: Thematic Review Series: Lipid Droplet Synthesis and Metabolism: from Yeast to Man. AB - Lipid droplets are evolutionarily conserved organelles where cellular fat storage and mobilization are exquisitely regulated. Recent studies have defined lipid droplets in C. elegans and explored how they are regulated by genetic and dietary factors. C. elegans offers unique opportunities to visualize lipid droplets at single-cell resolution in live animals. The development of novel microscopy techniques and protein markers for lipid droplets will accelerate studies on how nutritional states and subcellular organization are linked in vivo. Together with powerful tools for genetic and biochemical analysis of metabolic pathways, alteration in lipid droplet abundance, size, and distribution in C. elegans can be readily connected to whole-animal energy homeostasis, behavior, and life span. Therefore, further studies on lipid droplets in C. elegans promise to yield valuable insights that complement our knowledge gained from yeast, Drosophila, and mammalian systems on cellular and organismal fat storage. PMID- 22049245 TI - Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma. AB - The molecular determinants of thyroid follicular nodules are incompletely understood and assessment of malignancy is a diagnostic challenge. Since microRNA (miRNA) analyses could provide new leads to malignant progression, we characterised the global miRNA expression in follicular adenoma (FA) and follicular carcinoma (FC). Comparison of carcinoma and adenoma with normal thyroid revealed 150 and 107 differentially expressed miRNAs respectively. Most miRNAs were down-regulated and especially miR-199b-5p and miR-144 which were essentially lost in the carcinomas. Integration of the changed miRNAs with differentially expressed mRNAs demonstrated an enrichment of seed sites among up regulated transcripts encoding proteins implicated in thyroid tumourigenesis. This was substantiated by the demonstration that pre-miR-199b reduced proliferation when added to cultured follicular thyroid carcinoma cells. The down regulated miRNAs in FC exhibited a substantial similarity with down-regulated miRNAs in anaplastic carcinoma (AC) and by gene set enrichment analysis, we observed a significant identity between target mRNAs in FC and transcripts up regulated in AC. To examine the diagnostic potential of miRNA expression pattern in distinguishing malignant from benign nodules we employed a supervised learning algorithm and leave-one-out-cross-validation. By this procedure, FA and FC were identified with a negative predicted value of 83% (data generated by microarray platform) and of 92% (data generated by qRT-PCR platform). We conclude that follicular neoplasia is associated with major changes in miRNA expression that may promote malignant transformation by increasing the expression of transcripts encoding tumourigenic factors. Moreover, miRNA profiling may facilitate the diagnosis of carcinoma vs adenoma. PMID- 22049246 TI - Modeling of the variability of fatigue crack growth using cohesive zone elements. AB - By its nature, metal fatigue has random characteristics, leading to extensive scatter in the results. Both initiation and propagation of a fatigue crack can be seen as random processes. This manuscript develops a numerical analysis using cohesive zone elements allowing the use of one single model in the finite element simulation of the complete fatigue life. The present formulation includes a damage evolution mechanism that reflects gradual degradation of the cohesive strength under cyclic loading. The uncertainties inherent to the fatigue process are assumed to be caused by the variability of the material properties, which are modeled using random fields. An extrapolation scheme is proposed to reduce the computational time. First, the accuracy of the proposed formulation is assessed considering a deterministic crack growth problem. Second, the effect of randomness in the material properties on the total fatigue life of a structure is then analyzed. PMID- 22049247 TI - Parametric Diffuse Optical Imaging in Reflectance Geometry. AB - Diffuse optical imaging (DOI) is a model-based technique used for noninvasive characterization of subsurface tissue function and structure. Compared to more common transmission geometries, reflectance DOI has the advantage of being portable and easily implemented in a clinical setting. However, reflectance measurements are generally not compatible with conventional DOI image reconstruction methods because they typically provide a limited number of unique tissue views. In this paper, we describe a fast and reliable DOI image reconstruction method based on parameterization of tissue and tumor optical contrast, using physiological a priori knowledge. The reconstruction method is formulated within the general Bayesian inversion framework and is capable of handling both model and measurement errors. Simulations are carried out to illustrate the application of this approach, using a limited number of source detector combinations. It is also shown that parametric reflectance DOI is robust to model misspecifications and measurement noise. PMID- 22049248 TI - A simple technique for measuring buoyant weight increment of entire, transplanted coral colonies in the field. AB - Estimating the impacts of global and local threats on coral reefs requires monitoring reef health and measuring coral growth and calcification rates at different time scales. This has traditionally been mostly performed in short-term experimental studies in which coral fragments were grown in the laboratory or in the field but measured ex situ. Practical techniques in which growth and measurements are performed over the long term in situ are rare. Apart from photographic approaches, weight increment measurements have also been applied. Past buoyant weight measurements under water involved a complicated and little used apparatus. We introduce a new method that combines previous field and laboratory techniques to measure the buoyant weight of entire, transplanted corals under water. This method uses an electronic balance fitted into an acrylic glass underwater housing and placed atop of an acrylic glass cube. Within this cube, corals transplanted onto artificial bases can be attached to the balance and weighed at predetermined intervals while they continue growth in the field. We also provide a set of simple equations for the volume and weight determinations required to calculate net growth rates. The new technique is highly accurate: low error of weight determinations due to variation of coral density (< 0.08%) and low standard error (< 0.01%) for repeated measurements of the same corals. We outline a transplantation technique for properly preparing corals for such long-term in situ experiments and measurements. PMID- 22049249 TI - Water-Soluble Polypeptides with Elongated, Charged Side Chains Adopt Ultra-Stable Helical Conformations. AB - Water-soluble polypeptides adopting alpha-helical conformations with unprecedented high helicities were obtained by elongating the charge-containing side chains of the constituent amino acids to allow the terminal charges to be situated distally from the peptide backbone. Poly(gamma-(4 aminoethylthiopropoxyl)-benzyl-(L)-glutamate) (PAOBLG-AET) with a charge-peptide backbone distance of 17 sigma-bonds exhibited a remarkably high helical content (81%) at a degree of polymerization as low as 10. The helical conformations of these short polypeptides were very stable against various harsh, protein denaturing conditions, such as extreme pH, high temperature, and high salt or urea concentrations. PMID- 22049250 TI - Evaluating scaled windowed variance methods for estimating the Hurst coefficient of time series. AB - Three-scaled windowed variance methods (standard, linear regression detrended, and brdge detrended) for estimating the Hurst coefficient (H) are evaluated. The Hurst coefficient, with 0 < H < 1, characterizes self-similar decay in the time series autocorrelation function. The scaled windowed variance methods estimate H for fractional Brownian motion (fBm) signals which are cumulative sums of fractional Gaussian noise (fGn) signals. For all three methods both the bias and standard deviation of estimates are less than 0.05 for series having N >= 2(9) points. Estimates for short series (N < 2(8)) are unreliable. To have a 0.95 probability of distinguishing between two signals with true H differing by 0.1, more than 2(15) points are needed. All three methods proved more reliable (based on bias and variance of estimates) than Hurst's rescaled range analysis, periodogram analysis, and autocorrelation analysis, and as reliable as dispersional analysis. The latter methods can only be applied to fGn or differences of fBm, while the scaled windowed variance methods must be applied to fBm or cumulative sums of fGn. PMID- 22049251 TI - Analyzing exact fractal time series: evaluating dispersional analysis and rescaled range methods. AB - Precise reference signals are required to evaluate methods for characterizing a fractal time series. Here we use fGp (fractional Gaussian process) to generate exact fractional Gaussian noise (fGn) reference signals for one-dimensional time series. The average autocorrelation of multiple realizations of fGn converges to the theoretically expected autocorrelation. Two methods commonly used to generate fractal time series, an approximate spectral synthesis (SSM) method and the successive random addition (SRA) method, do not give the correct correlation structures and should be abandoned. Time series from fGp were used to test how well several versions of rescaled range analysis (R/S) and dispersional analysis (Disp) estimate the Hurst coefficient (0 < H < 1.0). Disp is unbiased for H < 0.9 and series length N >= 1024, but underestimates H when H > 0.9. R/S-detrended overestimates H for time series with H < 0.7 and underestimates H for H > 0.7. Estimates of H(H) from all versions of Disp usually have lower bias and variance than those from R/S. All versions of dispersional analysis, Disp, now tested on fGp, are better than we previously thought and are recommended for evaluating time series as long-memory processes. PMID- 22049252 TI - High mobility, low voltage operating C(60) based n-type organic field effect transistors. AB - We report on C(60) based organic field effect transistors (OFETs) that are well optimized for low voltage operation. By replacing commonly used dielectric layers by thin parylene films or by utilizing different organic materials like divinyltetramethyldisiloxane-bis(benzocyclo-butene) (BCB), low density polyethylene (PE) or adenine in combination with aluminum oxide (AlOx) to form a bilayer gate dielectric, it was possible to significantly increase the capacitance per unit area (up to two orders of magnitude). The assembly of metal oxide and organic passivation layer combines the properties of the high dielectric constant of the metal oxide and the good organic-organic interface between semiconductor and insulator provided by a thin capping layer on top of the AlOx film. This results in OFETs that operate with voltages lower than 500 mV, while exhibiting field effect mobilities exceeding 3 cm(2) V(-1) s(-1). PMID- 22049262 TI - NEURO-ONCOLOGIC PHYSICAL THERAPY FOR THE OLDER PERSON. AB - Due to the uncertainty of the course of diagnoses, patients with neuro oncological malignancies present challenges to the physical therapist. At times, the presentation of impairments and disabilities of these patients with neuro oncological diagnoses do not necessarily coincide with the involved area of the brain or spinal cord. It is our intention to provide guidance to the physical therapist who will be working with these patients with neuro-oncological diagnoses, in hopes that their encounters will be more productive and meaningful. This article describes a brief overview of common central nervous system malignancies, its medical treatment, as well as possible complications and side effects that would need to be considered in rehabilitating these patients. Special consideration is given to the elderly patients with neuro-oncological diagnoses. Pertinent physical therapy assessments and interventions are discussed. PMID- 22049263 TI - Large Sample Group Independent Component Analysis of Functional Magnetic Resonance Imaging Using Anatomical Atlas-Based Reduction and Bootstrapped Clustering. AB - Independent component analysis (ICA) is a popular method for the analysis of functional magnetic resonance imaging (fMRI) signals that is capable of revealing connected brain systems of functional significance. To be computationally tractable, estimating the independent components (ICs) inevitably requires one or more dimension reduction steps. Whereas most algorithms perform such reductions in the time domain, the input data are much more extensive in the spatial domain, and there is broad consensus that the brain obeys rules of localization of function into regions that are smaller in number than the number of voxels in a brain image. These functional units apparently reorganize dynamically into networks under different task conditions. Here we develop a new approach to ICA, producing group results by bagging and clustering over hundreds of pooled single subject ICA results that have been projected to a lower-dimensional subspace. Averages of anatomically based regions are used to compress the single subject ICA results prior to clustering and resampling via bagging. The computational advantages of this approach make it possible to perform group-level analyses on datasets consisting of hundreds of scan sessions by combining the results of within-subject analysis, while retaining the theoretical advantage of mimicking what is known of the functional organization of the brain. The result is a compact set of spatial activity patterns that are common and stable across scan sessions and across individuals. Such representations may be used in the context of statistical pattern recognition supporting real-time state classification. PMID- 22049264 TI - Modelling the relationship between body fat and the BMI. AB - OBJECTIVE: Given the increasing concerns about the levels of obesity being reached throughout the world, this paper analyses the relationship between the most common index of obesity, the BMI, and levels of body fat. RESEARCH METHODS AND PROCEDURES: The statistical relationship, in terms of functional form, between body fat and BMI is analysed using a large data set which can be categorized by race, sex and age. RESULTS: Irrespective of race, body fat and BMI are linearly related for males, with age entering logarithmically and with a positive effect on body fat. Caucasian males have higher body fat irrespective of age, but African American males' body fat increases with age faster than that of Asians and Hispanics. Age is not a significant predictor of body fat for females, where the relationship between body fat and BMI is nonlinear except for Asians. Caucasian females have higher predicted body fat than other races, except at low BMIs, where Asian females are predicted to have the highest body fat. DISCUSSION: Using BMIs to make predictions about body fat should be done with caution, as such predictions will depend upon race, sex and age and can be relatively imprecise. The results are of practical importance for informing the current debate on whether standard BMI cut-off values for overweight and obesity should apply to all sex and racial groups given that these BMI values are shown to correspond to different levels of adiposity in different groups. PMID- 22049265 TI - Ridge regression for longitudinal biomarker data. AB - Technological advances facilitating the acquisition of large arrays of biomarker data have led to new opportunities to understand and characterize disease progression over time. This creates an analytical challenge, however, due to the large numbers of potentially informative markers, the high degrees of correlation among them, and the time-dependent trajectories of association. We propose a mixed ridge estimator, which integrates ridge regression into the mixed effects modeling framework in order to account for both the correlation induced by repeatedly measuring an outcome on each individual over time, as well as the potentially high degree of correlation among possible predictor variables. An expectation-maximization algorithm is described to account for unknown variance and covariance parameters. Model performance is demonstrated through a simulation study and an application of the mixed ridge approach to data arising from a study of cardiometabolic biomarker responses to evoked inflammation induced by experimental low-dose endotoxemia. PMID- 22049266 TI - Antihypertensive medication use and change in kidney function in elderly adults: a marginal structural model analysis. AB - BACKGROUND: The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model. METHODS: Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989-1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring. RESULTS: The mean annual decline in eGFR was 2.41 +/- 4.91 mL/min/1.73 m(2). In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m(2) per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (-0.13, 4.59) ml/min/1.73 m(2) per year slower decline in eGFR. CONCLUSION: In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings. PMID- 22049267 TI - Commentary on "Principal stratification - a goal or a tool?" by Judea Pearl. AB - This commentary takes up Pearl's welcome challenge to clearly articulate the scientific value of principal stratification estimands that we and colleagues have investigated, in the area of randomized placebo-controlled preventive vaccine efficacy trials, especially trials of HIV vaccines. After briefly arguing that certain principal stratification estimands for studying vaccine effects on post-infection outcomes are of genuine scientific interest, the bulk of our commentary argues that the "causal effect predictiveness" (CEP) principal stratification estimand for evaluating immune biomarkers as surrogate endpoints is not of ultimate scientific interest, because it evaluates surrogacy restricted to the setting of a particular vaccine efficacy trial, but is nevertheless useful for guiding the selection of primary immune biomarker endpoints in Phase I/II vaccine trials and for facilitating assessment of transportability/bridging surrogacy. PMID- 22049268 TI - On causal mediation analysis with a survival outcome. AB - Suppose that having established a marginal total effect of a point exposure on a time-to-event outcome, an investigator wishes to decompose this effect into its direct and indirect pathways, also known as natural direct and indirect effects, mediated by a variable known to occur after the exposure and prior to the outcome. This paper proposes a theory of estimation of natural direct and indirect effects in two important semiparametric models for a failure time outcome. The underlying survival model for the marginal total effect and thus for the direct and indirect effects, can either be a marginal structural Cox proportional hazards model, or a marginal structural additive hazards model. The proposed theory delivers new estimators for mediation analysis in each of these models, with appealing robustness properties. Specifically, in order to guarantee ignorability with respect to the exposure and mediator variables, the approach, which is multiply robust, allows the investigator to use several flexible working models to adjust for confounding by a large number of pre-exposure variables. Multiple robustness is appealing because it only requires a subset of working models to be correct for consistency; furthermore, the analyst need not know which subset of working models is in fact correct to report valid inferences. Finally, a novel semiparametric sensitivity analysis technique is developed for each of these models, to assess the impact on inference, of a violation of the assumption of ignorability of the mediator. PMID- 22049269 TI - Principal stratification and attribution prohibition: good ideas taken too far. AB - Pearl's article provides a useful springboard for discussing further the benefits and drawbacks of principal stratification and the associated discomfort with attributing effects to post-treatment variables. The basic insights of the approach are important: pay close attention to modification of treatment effects by variables not observable before treatment decisions are made, and be careful in attributing effects to variables when counterfactuals are ill-defined. These insights have often been taken too far in many areas of application of the approach, including instrumental variables, censoring by death, and surrogate outcomes. A novel finding is that the usual principal stratification estimand in the setting of censoring by death is by itself of little practical value in estimating intervention effects. PMID- 22049270 TI - Nanomanipulation of biological samples using a compact atomic force microscope under scanning electron microscope observation. AB - We introduce a compact nanomanipulator that can be operated inside the sample chamber of a scanning electron microscope (SEM) for biological sample manipulation. The design of the nanomanipulator is based on that of an atomic force microscope (AFM). A self-sensitive cantilever is used to realize the compact body and thus it is possible to put a pair of the standalone AFM units on the sample stage in the SEM chamber. Using this system, we accomplished nanodissection of biological samples as well as AFM imaging under SEM observation. We then fabricated the surface of a rat renal glomerulus by scan scratching and succeeded in making a small hole on the wall of a blood capillary. As a result, it was possible to observe the internal structure of the capillary, which had been hidden beneath the surface wall. Furthermore, using two AFM units on the sample stage of the SEM, we successfully dissected the lens fiber cells taken from a rat eye in a multi-probe operation using the two cantilevers. This system is expected to become a very useful tool for micro- and nanometer-scale anatomy and engineering applications. PMID- 22049271 TI - Cytotoxic evaluation of doxorubicin in combination with simvastatin against human cancer cells. AB - Doxorubicin is a broad spectrum antibiotic used in the treatment of cancers. Its dose dependent cardiotoxicity is the most serious side effect causing withdrawal of drug from hard chemotherapeutic regimen. Statins are shown to be cytotoxic in concentrations higher than the effective doses for the treatment of hypercholesterolemia (40 mg/day). Co-administration of statins and chemotherapeutic agents suppose to be synergic although there are some controversies in the literature. In this study, cytotoxic effects of doxorubicin alone and in combination with simvastatin on Hela tumor cell line were evaluated. Different concentration of doxorubicin and simvastatin were added to the cultured cells and incubated for 72 h. Cell survival was evaluated using MTT and trypan blue exclusion assays. The results indicated that simvastatin in low concentration (0.25 MUM) seems to be growth stimulator although cell viability was reduced in concentrations of >=2 MUM. Doxorubicin alone at all tested concentrations (0.1, 1 and 2 MUM) was a cell growth inhibitor. It was also shown that percent cell viability was reduced in a decreasing manner with the following protocols: 1) co-administration of doxorubicin and simvastatin in different concentrations; 2) addition of simvastatin after incubation of cells with doxorubicin and 3) addition of doxorubicin after incubation of cells with simvastatin. It could be concluded that between 3 tested protocols combination of doxorubicin and simvastatin after 72 h incubation, showed the highest cytotoxicity against Hela cells. PMID- 22049272 TI - Quantification of ergovaline using HPLC and mass spectrometry in Iranian Neotyphodium infected tall fescue. AB - Ergovaline, the main ergopeptine alkaloid produced in tall fescue (Fescue arundinacea Schreb.) infected with endophyte (Neotyphodium coenophialum Morgan- Jones & Gams), is known to cause tall fescue toxicosis. This study was conducted to examine the presence of fungal endophytes in five populations of tall fescue collected from various regions of Iran. The existence of Neotyphodium mycelia in the tissues of the samples was confirmed by microscopic examination, and the isolation was performed from leaf tissues of the hosts on potato dextrose agar. All isolates were confirmed as the Neotyphodium species by PCR, using specific primers. Mass detection and determination of ergovaline were performed by HPLC at three plant growth stages. Ergovaline was detected in all isolates, with the mean concentrations of 0.24 to 3.48 MUg/g dry matter of different populations for the whole three plant growth stages. The differences in ergovaline content between plant populations and sampling time were statistically significant. This is the first report of ergovaline content in endophyte infected Fescue arundinacea from natural grasslands in Iran. PMID- 22049273 TI - Pharmaceutical and nutraceutical effects of Pinus pinaster bark extract. AB - In everyday life, our body generates free radicals and other reactive oxygen species which are derived either from the endogenous metabolic processes (within the body) or from external sources. Many clinical and pharmacological studies suggest that natural antioxidants can prevent oxidative damage. Among the natural antioxidant products, Pycnogenol((r)) (French Pinus pinaster bark extract) has been received considerable attention because of its strong free radical scavenging activity against reactive oxygen and nitrogen species. P. pinaster bark extract (PBE) contains polyphenolic compounds (these compounds consist of catechin, taxifolin, procyanidins of various chain lengths formed by catechin and epicatechin units, and phenolic acids) capable of producing diverse potentially protective effects against chronic and degenerative diseases. This herbal medication has been reported to have cardiovascular benefits, such as vasorelaxant activity, angiotensin-converting enzyme inhibiting activity, and the ability to enhance the microcirculation by increasing capillary permeability. Moreover, effects on the immune system and modulation of nitrogen monoxide metabolism have been reported. This article provides a brief overview of clinical studies describing the beneficial and health-promoting effects of PBE. PMID- 22049274 TI - Effects of extract and essential oil of Rosmarinus officinalis L. on TNBS-induced colitis in rats. AB - Rosmarinus officinalis L. (Family Lamiaceae) popularly named rosemary, is a common household plant grown around the world, including Iran. Rosemary aerial parts are used as flavoring agent in foods, beverages, and cosmetic preparations and have various traditional uses in ethnomedicine including: analgesic, anti inflammatory, anti-rheumatic, spasmolytic, carminative and choleretic applications. This study was carried out to investigate the effects of rosemary leaves hydroalcoholic extract (RHE) and essential oil (REO) in a well-defined model of experimental colitis induced by trinitrobenzene sulfonic acid (TNBS) in rats. Different doses of RHE (100, 200 and 400 mg/kg) and REO (100, 200 and 400 MUl/kg) were administered orally and intraperitoneally (100, 400 mg/kg and 100, 400 MUl/kg) to male Wistar rats (n=6), 6 h after colitis induction and continued for 5 days by intracolonic instillation of 0.25 ml TNBS (80 mg/kg)/ethanol 50% v/v. Wet colon weight/length ratio was measured and tissue damage scores as well as indices of colitis were evaluated both macroscopically and histopathologically. RHE and REO at all test doses used were effective to reduce colon tissue lesions and colitis indices while greater doses were significantly effective to diminish histopathologic parameters irrespective to the route of administration. Administration of oral prednisolone, Asacol((r)) (mesalazine microgranules) and parenteral hydrocortisone acetate were effective to reduce colon tissue injures as well. These data suggest that RHE and REO are both effective to possess anti-colitic activity, and reinforce the use of this plant as a remedy for inflammatory bowel diseases in traditional medicine. PMID- 22049275 TI - Application of different chemometric tools in QSAR study of azolo-adamantanes against influenza A virus. AB - Quantitative relationships between molecular structure and azolo-adamantanes derivatives were discovered by different chemometric tools including factor analysis based multiple linear regressions (FA-MLR), principle component regression analysis (PCRA), and genetic algorithm-partial least squares GA-PLS. The FA-MLR describes the effect of geometrical and quantum indices on enzyme inhibition activity of the studied molecules. The quality of PCRA equation was found to be better than those derived from FA-MLR. GA-PLS analysis indicated that the topological (IC4 and MPC06), constitutional (nf) and geometrical (G (N..S] parameters were the most significant ones on influenza A virus activity. Comparison of the different statistical methods employed revealed that GA-PLS represented superior results and it could explain and predict 85% and 77% of variances in the pIC(50) data, respectively. PMID- 22049276 TI - New tigliane-type diterpenoids from Euphorbia aellenii Rech. f. with immunomodulatory activity. AB - The cytotoxic chloroform fraction of Euphorbia aellenii Rech. F. (Euphorbiaceae) afforded two new phorbol diterpenoids: 4-deoxy-4alpha-phorbol-12-(2,3-dimethyl) butyrate-13-isobutyrate and 17-hydroxy-4-deoxy-4alpha-phorbol-12-(2,3-dimethyl) butyrate-13-isobutyrate. Their structures were elucidated by NMR and other spectroscopic methods. The immunomodulating potentials of the isolated compounds were tested using standard proliferation and chemiluminescence assays. Compound 2 showed moderate inhibitory activity against both T-cell proliferation and reactive oxygen species (ROS) production in whole blood with IC50 of 14.0 +/- 0.57 and 44.1 +/- 3.8 MUg/ml, respectively, while compound 1 was relatively inactive with IC50 >50 MUg/mL for T-cell proliferation, and >100 MUg/mL for ROS. PMID- 22049277 TI - Spasmolytic effect of root and aerial parts extract of Pycnocycla spinosa on neural stimulation of rat ileum. AB - Extract prepared from aerial part of Pycnocycla spinosa is a relaxant of rat ileum contractions. The objective of this research was to study the spasmolytic activity of P. spinosa root extract for comparison with the aerial part extract. Hydroalcoholic extracts were prepared by percolation method. A portion of rat ileum was removed and suspended under 1 g tension in Tyrode's solution at 37 degrees C and gassed with O(2). Isotonic contractions induced by electrical field stimulation (EFS), and KCl were recorded before and after addition of the extracts. Experiments were performed alongside time-matched vehicle controls. Both EFS responses are blocked by lidocaine (74 MUM), indicating that contractile responses are mediated by neuronal mechanism and partially was blocked by atropine. The root extract of P. spinosa (10-320 MUg/ml) inhibited both initial rapid (IC(50) = 71 +/- 11.9 MUg/ml) and secondary slow contraction (IC(50) = 56 +/- 7.8 MUg/ml) evoked by EFS (n=6) as well as the KCl response (IC(50) = 59 +/- 11.7 MUg/ml). The aerial part extract had a similar inhibitory effect on both KCl (IC(50) = 47 +/- 6.3 MUg/ml) and EFS responses. This study confirms the inhibitory effects of root extract of P. spinosa on rat ileum contraction. However, the root extract was not more effective than the aerial part extract. Therefore, the aerial parts extract of P. spinosa could be used as a suitable substitute for the root extract. PMID- 22049278 TI - Effect of five common anticonvulsant drugs on naloxone-precipitated morphine withdrawal in mice. AB - This study was designed to assess the effect of five common anticonvulsant drugs on naloxone-precipitated withdrawal syndrome in morphine-dependent mice. Male mice (25-35 g) were made dependent by increasing doses of morphine (30-90 mg/kg). At least three doses of phenytoin, carbamazepine, sodium valproate, lamotrigine and topiramate were injected i.p. to morphine-dependent mice 45 min prior to induction of withdrawal syndrome by naloxone (5 mg/kg, i.p.). Control animals received vehicle. Number of jumpings was counted and ptosis, tremor, piloerection and diarrhea were checked in a 30 min period started just after naloxone injection. Results showed that lamotrigine, phenytoin and sodium valproate were ineffective in suppression of withdrawal syndrome while carbamazepine produced a dose-dependent reduction of jumpings. Topiramate at the maxium applied dose (100 mg/kg) significantly reduced number of naloxone-elicited jumpings. It seems that carbamazepine by inhibition of N-Methyl-D-Aspartate (NMDA) receptors and topiramate by inhibiting kainite-activated (AMPA) receptor antagonists suppress morphine withdrawal syndrome but further studies are needed to have a definite conclusion. PMID- 22049279 TI - Production of chlorogenic acid in Varthemia persica DC (var. persica) callus cultures. AB - Chlorogenic acid, a pharmacologically important compound, is a phenolic compound that occurs in certain commonly used medicinal herbs. We looked for the presence of this compound in the callus cultures of Varthemia persica DC (var. persica). We have evaluated the conditions for establishment of callus cultures of V. persica and the in vitro production of chlorogenic acid. Callus was initiated by culturing seedling of V. persica on MS basal medium supplemented with different concentrations of kinetin, naphthalene acetic acid and 2,4-diphenoxy acetic acid. Also, the influence of light, and phytohormones on the production of chlorogenic acid was examined. Kinetin stimulated the production of chlorogenic acid. Replacement of 2,4-diphenoxy acetic acid with naphthalene acetic acid did not alter the chlorogenic acid production. The ability to induce the accumulation of chlorogenic acid in the V. persica callus cultures offers an opportunity to produce a phenolic compound with therapeutic value. PMID- 22049280 TI - The effect of acquiring life skills through humor on social adjustment rate of the female students. AB - BACKGROUND: Life skills have different effects on various aspects of the mental health. Social adjustment prepares adolescents for entering to the adulthood. On the other hand, humor and joking in the education is considered as a stress reducer and learning increaser. Therefore, the present study conducted aimed to determine the effect of acquiring life skills through humor on the social adjustment rate of the high school girls. METHODS: This was a two-group semi experimental study including three phases. The study population included 69 first year high school female students of Isfahan Department of Education district 3 who were selected in simple random sampling. First of all, the social adjustment rate was measured using California Personality Inventory. Thereafter, life skills education was conducted using humor during five sessions. Finally, a test was taken in order to assess the acquisition of the life skills in which passing score was required for re-completing the questionnaire. The data were analyzed using software SPSS(10) and independent and paired t-tests. RESULTS: The findings of the study indicated that the mean score of the social adjustment statistically had a significant difference in the intervention group before and after the intervention. Furthermore, statistically, there was a significant difference between mean score of the social adjustment in the control group and test group after conducting the intervention. CONCLUSIONS: The findings of the study indicated that life skills education has been increased through humor on the social adjustment rate of the high school girl students. Considering the efficacy of learning life skills on the social adjustment and results of the other studies which were in accordance with the present study, implementing such trainings with a new method comprehensively is recommended in the schools. PMID- 22049281 TI - A comparative study on the effects of Hypericum Perforatum and passion flower on the menopausal symptoms of women referring to Isfahan city health care centers. AB - BACKGROUND: With regard to an increase in the life expectancy for women and the consistency of the menopause age, a significant portion of women's age is passed after the menopause. Menopause is considered as a critical and sensitive period due to the changes and the disorders that are involved in it. Vasomotor symptoms, sleep disorders and psycho-mental changes are among the most prevalent symptoms of this period. Hormone therapy is a common treatment and it involves some problems for most individuals. The purpose of this study was to comparatively examine the effects of two herbal medications, Hypericum Perforatum and Passion Flower, on menopause symptoms. METHODS: This study was of a clinical-experimental type which was done in 1388 in Isfahan. The sample included 59 menopausal women who had the conditions for entering into the study. The individuals were selected via simple sampling and were assigned randomly into two groups of Hypericum Perforatum treatment group (30 women) and Passion Flower group (29 women). The required data were filled out through interview, Personal Characteristics Questionnaire, and Cooperman's Index for menopause symptoms in three stages of pre-intervention, the third week of intervention, and the sixth week of intervention. The results were analyzed by descriptive and inferential statistical methods and the statistical software of SPSS. RESULTS: The findings showed that the average score of menopause symptoms in two treatment groups of Hypericum Perforatum and Passion Flower had a significant decrease throughout the third and the sixth weeks of study (p < 0.05). In addition, there was no statistically significant difference between the two groups and both herbs equally resulted in a decrease in the menopause symptoms scores (p > 0.05). CONCLUSIONS: With regard to the effects of Hypericum Perforatum and Passion Flower on treating menopause precocious symptoms (vasomotor signs, insomnia, depression, anger, headache, etc.), these two herbs can be used as an alternative treatment for individuals who cannot, whatsoever, use hormone therapy. PMID- 22049282 TI - The effectiveness of stress management training program on depression, anxiety and stress of the nursing students. AB - BACKGROUND: Stress has been defined as a barrier to concentration, problem solving, decision making, and other necessary abilities for students' learning; it also has some symptoms and illnesses in the students such as depression and anxiety. In reviewing stress and its consequences, the methods of coping with stress in the method of response to it would be more important than the nature of stress itself. Therefore, this study aimed to determine the effectiveness of stress management training program on depression, anxiety and stress rate of the nursing students. METHODS: This parallel group randomized quasi-experimental trial, was done on 68 Bs nursing students of Nursing and Midwifery School in Isfahan University of Medical Sciences from 2010 to 2011. The questionnaires of this study consisted of individual characteristics and Depression, Anxiety and Stress Scale (DASS-42). In a random fashion, The intervention group was trained with stress management training program in 8 two hours sessions, twice a week. The questionnaires were completed by both groups before, after and one month after the study. RESULTS: The results of the study indicated that there was no significant difference before the intervention in depression, anxiety and stress mean scores in the two groups. After the intervention, the mean scores of anxiety and stress in the intervention group was 5.09 (4.87) and 8.93 (6.01) and in the control group was 10 (6.45) and 13.17 (7.20), that reduction in depression mean score was significantly greater in the intervention group in the control group (p = 0.040). Furthermore, the mean scores of anxiety and stress showed a significant difference between the two groups (Anxiety p = 0.001; Stress p = 0.011); this reduction also had been remained after a month. CONCLUSIONS: According to the results of the present study, holding stress management training program workshops in different courses of the mental health department can improve mental health of the students. PMID- 22049283 TI - The role of community health nurses in behavioral modification of parents of children with behavioral disorders in primary schools in Isfahan. AB - BACKGROUND: Mental health is of great importance in childhood and the foundation of personality of every individual is laid during this period. Moreover, behavioral problems are common in children, and a lot of the individual, familial, and social disorders originate from the fact that these problems are not treated at the right time. More important is that the behavioral problems of children are rooted in the behavior and upbringing of parents. Therefore, we carried out the present study to investigate the role of community health nurses in modifying the behavior of parents whose children have behavioral problems. METHODS: This research was a pre- and post-training quasi-experimental study. The study was carried out with the participation of the parents of 44 first-grade primary school children with reported behavioral problems. The instrument used in the study was a self-made questionnaire. The data was analyzed by SPSS software, using descriptive and inferential statistical methods (t-test and repeated ANOVA). RESULTS: The mean scores of parents' behavior before, immediately after, and one month after training exhibited a significant difference in both fathers and mothers (p = 0.04 in fathers and p < 0.001 in mothers). Moreover, the mean scores of mothers before and immediately after training and also before and one month after training showed a significant difference (p < 0.001 and p < 0.001, respectively). However, the mean scores of mothers immediately after and one month after training were not significantly different (p=0.53). Furthermore, the mean scores of fathers before and immediately after training and also before and one month after training were significantly different (p < 0.001 and p < 0.001, respectively). But, the mean scores of fathers immediately after and one month after training did not show a significant difference (p = 0.33). CONCLUSIONS: Since the group training of parents led to a change in their behavior towards children, it is advisable to prepare and implement such programs. PMID- 22049284 TI - Reviewing sexual function after delivery and its association with some of the reproductive factors. AB - BACKGROUND: Desirable sexual function has an important role in strengthening the marital life of the couples. Sexual disorders can cause mental pressure and affect quality of life and marital relationship. METHODS: This was a descriptive analytical study in one group and one phase covering multivariables. The study sample included 384 women after delivery period that had the following inclusion criteria: the age of at least 18 years, delivery in 38-42 pregnancy weeks, primiparous and multiparous women, living in the city, single pregnancy, and six weeks to twelve months elapsed from the delivery. The required data such as reproductive and sexual function index were collected through reporting questionnaire. The data were analyzed using descriptive and inferential statistical methods using software SPSS. RESULTS: The findings of the study indicated that the most prevalent disorder of the sexual relationship in postpartum was dyspareunia and the least prevalent was the sexual desire. The majority of the study sample (77.1%) had marital satisfaction and 58.6% had the desired sexual function. There was no significant association between sexual function and delivery, age, the type of delivery and breastfeeding, but there was a significant association for other factors such as the time elapsed after the delivery and primiparity or multiparity (p < 0.01). CONCLUSIONS: It is recommended that sexual problems after delivery be placed on the list of health teaching issues to pass easily this period of time. Women should be assured that these problems gradually would be improved and they should learn using proper techniques to decrease dyspareunia which is a sexual disorder in postpartum period. PMID- 22049285 TI - Evaluation of quality of working life and its association with job performance of the nurses. AB - BACKGROUND: Nurses often complain about overwork and underpay. It seems that the association between "quality of working life" (QWL) and the degree of nurses' involvement in their carrier is the critical factor in achieving a higher level of quality of care. This study aimed to assess the quality of working life and its association with "job performance" of the nurses in educational hospitals affiliated to Isfahan University of Medical Sciences in 2007. METHODS: This was a descriptive-correlation study. Target population included all the nurses who were employed in hospitals affiliated to Isfahan University of Medical Sciences. Sample size was 120 of the mentioned nurses. Sampling method was stratified random and data collection tool was a questionnaire. Data analysis was done using mean, frequency distribution and spearman test. RESULTS: Finding of the study showed that the most common kind of quality of working life in the nurses (56.7%) was moderate one. The most frequent nurses' task performance (79.2%) was also related to the moderate performance. There was a direct and significant relationship between job performance and quality of working life in all the aspects. CONCLUSIONS: According to the research findings, it is important to consider the workplace and quality of working life of the nurses for improving productivity and performance of the nurses. Organization and nursing managers should use programs that can improve quality of working life of the nurses. PMID- 22049286 TI - The effects of supine and prone positions on oxygenation in premature infants undergoing mechanical ventilation. AB - BACKGROUND: Since the use of high concentrations of oxygen in infants may lead to chronic lung problems, using proper methods of care in infants under mechanical ventilation is one of the most important measures in NICU. This study aimed to investigate the effects of prone and supine positions on oxygenation (SPO(2)) in premature infants under mechanical ventilation and comparing infants' oxygenation in the two positions. METHODS: In across over non randomized clinical trial study, 32 preterm infants under mechanical ventilation who had inclusion criteria were enrolled in simple convenient method. Firstly, they were placed in supine position for 120 minutes and further in prone position for 120 minutes .Their SPO(2) were monitored by pulse oximeter continuously and was recorded every minute. Data analysis was done using Software SPSS(15) by ANOVA test and post hoc test. RESULTS: The data showed that during 120 minutes of exposure of infants in each position there were no significant changes in SPO(2). In addition, the SPO(2) levels in the prone position were significantly higher than the SPO(2) levels in the supine position from 15(th) minute to 120(th) minute (to the end). CONCLUSIONS: Neonatal positioning in prone position is a simple, non-invasive, and free of charge method that could lead to improve oxygenation in infants undergoing mechanical ventilation. PMID- 22049287 TI - Effect of aromatherapy on the quality of sleep in ischemic heart disease patients hospitalized in intensive care units of heart hospitals of the Isfahan University of Medical Sciences. AB - BACKGROUND: Sleep disorder is one of the common problems patients face in ICU and CCU and it is usually treated by sleeping pills. Nowadays, the complementary medicine is highly considered because of its effectiveness and safety. Aromatherapy is one of the holistic nursing cares which sees human beings as a biological, mental and social unit while the psychological dimension has the central role. Each of these dimensions is dependent on each other and is affected by each other. Therefore, it is fundamental for nurses to provide aromatherapy in their clinical performance. Aromatherapy helps treatment of diseases by using vegetable oils and it seems to be effective in reducing sleeplessness. METHODS: This was a clinical trial on 64 patients (male and female) hospitalized in CCU in Al-zahra and Chamran hospitals. The intervention included 3 nights, each time 9 hours aromatherapy with lavender oil for the experiment group, while the controls received no intervention. Both groups filled out the SMHSQ that includes 11 items to assess sleep quality before and after intervention. RESULTS: Data analysis showed that the mean scores of sleep quality in the two groups of experiment and control were significantly different after the aromatherapy with lavender oil (p < 0.001). CONCLUSIONS: Quality of sleep in ischemic heart disease patients was significantly improved after aromatherapy with lavender oil. Therefore, using aromatherapy can improve the quality of their sleep and health. PMID- 22049288 TI - Effect of aromatherapy on pruritus relief in hemodialysis patients. AB - BACKGROUND: Pruritus is one of the commonest problems in patients with end-stage renal failure undergoing hemodialysis. Pruritus is an irritating symptom which can directly affect the life quality of patients with chronic renal failure. However, available treatments have failed to relieve the symptom and kidney transplant remains the definite treatment of the problem. A recently proposed treatment for pruritus is the use of complementary medicine. Thus, the aim of this research is to study the effect of aromatherapy on pruritus relief in hemodialysis patients. METHODS: The study is a pre- and post-clinical trial, carried out in dialysis centers of Isfahan University of Medical Sciences in 2009. Sample was performed using convenient sampling method and the participants were selected from among the patient who received hemodialysis three times a week for 3-5 hours and had pruritus scores above 3. All the participants received seven minutes of hand massage in the non-fistulated hand with 3-5 ml of lavender, mint, and tea tree oils at 5% concentration for six sessions (two weeks). The data of the study were analyzed using descriptive and inferential statistics by SPSS software, version 16. RESULTS: Twenty patients with end-stage renal failure who had pruritus fulfilled the course of the study. Data analysis indicated that aromatherapy significantly relieved pruritus (p < 0.05). CONCLUSIONS: Aromatherapy can significantly relieve pruritus in hemodialysis patients. PMID- 22049289 TI - Do nurses provide holistic care to cancer patients? AB - BACKGROUND: In order to support cancer patients, nurses need to identify different physio-psycho- social needs of patients using a holistic approach. Focusing on Quality of Life (QoL) is congruent with the philosophy of a holistic approach in nursing. The main aim of this research study thus was to identify the level of agreement between cancer patients and nurses about cancer patients' QoL. METHODS: The study was a survey which was completed in 2008. 166 cancer patients and 95 nurses were conveniently recruited from three major hospitals in Adelaide, Australia. Each patient and nurse was invited to complete the World Health Organization Quality of Life Brief (WHOQoL-BREF) questionnaire separately. This questionnaire considers QoL across four domains or dimensions: physical health, psychological health, social relationship and environment. RESULTS: The proportion of the exact agreement between the two groups was 34.9%, 34.5%, 33.8% and 36.9% for the physical, psychological, social relationship, and environmental QoL domains, respectively. CONCLUSIONS: Results may indicate that nurses do not have a holistic understanding of cancer patients' QoL. QoL tools like the World Health Organization Quality of Life Brief (WHOQoL-BREF) might be used as guidelines for nurses to assess cancer patients' QoL rather than relying heavily on their perceptions and intuitions. The results provide some implications for Iran. PMID- 22049290 TI - Comparing the effects of Yasmin(r) and LD (low-dose estrogen) as contraceptive methods on menstrual cycle changes in women referred to the health care centers of Isfahan. AB - BACKGROUND: One of the biggest problem today that most developing countries are faced with is the uncontrolled population growth; a serious threat to the international community. One of the most accessible contraceptive methods is the hormonal methods in which low-dose estrogen (LD) combined pills are considered as the most common among them. The most important reason for discontinuation of the combination pills is the side effects and following the discontinuation, it can lead to unwanted pregnancy. Promotion of more new methods and providing better methods with lesser side effects can be an important step towards solving some of the problems and increasing the usage percentages of contraceptive methods. This study therefore aimed to compare the effects of Yasmin and LD on menstrual cycle changes. METHODS: In this clinical trial study, 60 women referred to the Family Planning Health Center of Isfahan in 2008 were studied that finally after the sample loss, 27 and 24 samples were placed in Yasmin and LD groups, respectively. A questionnaire was used in order to collect the data. Content validity test and re-test also were used to confirm the validity and reliability of the questionnaire. To analyze the data, SPSS software and descriptive and inferential statistical methods were used. RESULTS: The results of this study indicated that the bleeding rate in the Yasmin group within the next six month compared to taking them before was significantly lower than that in LD group (p = 0.02); but there was no significant difference in terms of menstrual bleeding duration and the two menstruation interval between the two groups (p = 0.2). There was no significant difference between the Yasmin and LD groups in terms of delay in menstruation and dysmenorrheal. Spotting rate significantly was higher in Yasmin group than that in LD group (p = 0.02). There was a significant reduction in terms of bleeding rate changes and menstrual bleeding duration in both Yasmin and LD group at the following next six months in comparison with before the consumption (p < 0.05). CONCLUSIONS: According to the results obtained, the oral combination of Yasmin pills has fewer side effects than LD pills. Therefore, it is recommended to start using Yasmin pill in the family planning units in Iran. PMID- 22049291 TI - The effect of relaxation techniques to ease the stress in infertile women. AB - BACKGROUND: Infertility causes psychological and emotional tension in the couples and makes severe stress on infertile men and women. Relaxation technique is one of the methods that reduces the stress and can balance the human's emotions. This study aimed to determine the effect of relaxation on the infertile women's stress score. METHODS: This was a semi-experimental and clinical trial study. Participants randomly divided into two groups. At the beginning, the stress scores were assessed in both groups using Newton's infertility stress questionnaire. The participants' stress scores were evaluated and then, the relaxation technique was implemented on the intervention group. This technique was performed in twelve sessions. All the questionnaires were completed under supervision of the researcher after embryo was transferred to the uterus (after 2 weeks) and before conducting the pregnancy test. RESULTS: Independent t-test showed that the total stress score did not have a significant difference in groups before the intervention (p > 0.05) whereas independent t-test indicated a significant difference in stress scores between the two groups after the intervention (p < 0.05). Stress score was higher in the control group in comparison with the intervention group. CONCLUSIONS: Relaxation technique can reduce the stress score in infertile women as a complementary and alternative medicine method. PMID- 22049292 TI - Plasma retinol-binding protein predicts plasma retinol concentration in both infected and uninfected Cameroonian women and children. AB - Variation in the relationship between plasma retinol-binding protein (RBP) and retinol (ROH) has implications for vitamin A (VA) status assessment using RBP. Our objectives were to identify factors affecting the RBP:ROH relationship and to derive and evaluate population-specific RBP cutoffs for VA deficiency (VAD) in Cameroon. Plasma RBP, C-reactive protein (CRP), alpha1-acid-glycoprotein (AGP), and ROH concentrations were compared in a subsample of women 15-49 y (n = 121) and children 12-59 mo (n = 123) included in a national survey conducted in 2009. Plasma RBP and ROH were highly correlated (r = 0.94 for women; r = 0.96 for children; P < 0.001). Pregnancy and lactation altered the RBP:ROH relationship in women, but obesity, elevated CRP and AGP, age, and VA status did not. Among children, age altered the RBP:ROH relationship, but sex, stunting, VA status, and elevated CRP and AGP did not. Cutoffs for VAD derived using regression analysis were <1.17 MUmol RBP/L for women (corresponding to <1.05 MUmol ROH/L) and <0.83 MUmol RBP/L for children (corresponding to <0.70 MUmol ROH/L). The sensitivity and specificity of derived cutoffs were 81.8 and 93.0% for women and 94.7 and 88.9% for children, respectively. The infection-adjusted prevalence of low VA status (<1.17 MUmol RBP/L) was 21.9% (95% CI = 18.7-25.0%) among women. Among children, the infection-adjusted prevalence of VAD (<0.83 MUmol RBP/L) was 35.0% (95% CI = 31.1-39.0%). In conclusion, VAD remains a public health problem in Cameroon. The RBP:ROH relationship should be considered in surveys using RBP to assess VA status, and use of population-specific cutoffs may be advisable. PMID- 22049293 TI - A salt reduction of 50% in bread does not decrease bread consumption or increase sodium intake by the choice of sandwich fillings. AB - Bread is a major contributor to sodium intake in many countries. Reducing the salt (NaCl) content in bread might be an effective way to reduce overall sodium intake. The objectives of this study were to examine the effects of gradually lowering the salt content in brown bread, with and without flavor compensation (KCl and yeast extract), on bread consumption and sodium intake compensation by choice of sandwich fillings. A total of 116 participants (age: 21 +/- 3 y; BMI: 22 +/- 2 kg/m2) consumed a buffet-style breakfast on weekdays for 4 wk. Participants received either regular bread (control group: n = 39), bread whose salt content was gradually lowered each week by 0, 31, 52, and 67% (reduced group: n = 38), or bread whose salt content was also gradually lowered each week but which was also flavor compensated (compensated group: n = 39). A reduction of up to 52% of salt in bread did not lead to lower consumption of bread compared to the control (P = 0.57), whereas less bread was consumed when salt was reduced by 67% (P = 0.006). When bread was flavor compensated, however, a reduction of 67% did not lead to lower consumption (P = 0.69). Salt reduction in bread (with and without flavor compensation) did not induce sodium intake compensation (P = 0.31). In conclusion, a salt reduction of up to 52% in bread or even up to 67% in flavor-compensated bread neither affected bread consumption nor choice of sandwich fillings. PMID- 22049294 TI - Both longer oral sensory exposure to and higher intensity of saltiness decrease ad libitum food intake in healthy normal-weight men. AB - Orosensory exposure to sweetness has been shown to be important in satiation, whereas the effect of exposure to a salty taste on satiation is not known. The primary objective was to investigate the effect of orosensory exposure time to and intensity of saltiness in soup on ad libitum intake. The secondary objective was to investigate the effect of intensity on bite size. Fifty-five healthy men consumed ad libitum from both a low-salt (LS) and a high-salt (HS) creamy tomato soup in 2 exposure time conditions ("long" and "short") and a free condition ("free"). Bites were administered and controlled via a pump. In the long condition, bites of 5 g were administered in 2 s at intervals of 5 s (exposure time: 24 s/min). In the short condition, bites of 15 g were administered in 3 s at intervals of 15 s (exposure time: 12 s/min). The eating rate was equal in the long and short conditions (60 g/min). In the free condition, participants adjusted their bite sizes at intervals of 15 s. The short condition resulted in ~34% higher ad libitum intake compared to the long condition (P < 0.001); there was no interaction with intensity. Ad libitum intake of HS soup was ~9% lower than LS soup (P < 0.001). The free condition showed that HS soup was consumed with smaller bite sizes during the first half of the intake period (P < 0.05). Longer orosensory exposure and higher saltiness intensity both decreased food intake, although orosensory exposure had more impact than intensity. Prolonging the orosensory exposure per food unit may be helpful to reduce food intake. PMID- 22049295 TI - Dietary energy density is associated with body weight status and vegetable intake in U.S. children. AB - The objective was to determine the relationship between dietary energy density (ED; kcal/g) and measured weight status in children. The present study used data from a nationally representative sample of 2442 children between 2 and 8 y old who participated in the 2001-2004 NHANES. Survey measures included 24-h dietary recall data, measurement of MyPyramid servings of various food groups, and anthropometry. The relationship among dietary ED, body weight status as calculated using the 2000 CDC growth charts, and food intake was evaluated using quartiles of ED. Additionally, other dietary characteristics associated with ED among children are described. Specific survey procedures were used in the analysis to account for sample weights, unequal selection probability, and the clustered design of the NHANES sample. In this sample, dietary ED was positively associated with body weight status in U.S. children aged 2-8 y. Obese children had a higher dietary ED than lean children (2.08 +/- 0.03 vs. 1.93 +/- 0.05; P = 0.02). Diets high in ED were also found to be associated with greater intakes of energy and added sugars, more energy from fat; and significantly lower intake of fruits and vegetables. Interventions that lower dietary ED by means of increasing fruit and vegetable intake and decreasing fat consumption may be an effective strategy for reducing childhood obesity. PMID- 22049296 TI - A high intake of saturated fatty acids strengthens the association between the fat mass and obesity-associated gene and BMI. AB - Evidence that physical activity (PA) modulates the association between the fat mass and obesity-associated gene (FTO) and BMI is emerging; however, information about dietary factors modulating this association is scarce. We investigated whether fat and carbohydrate intake modified the association of FTO gene variation with BMI in two populations, including participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 1069) and in the Boston Puerto Rican Health (BPRHS) study (n = 1094). We assessed energy, nutrient intake, and PA using validated questionnaires. Genetic variability at the FTO locus was characterized by polymorphisms rs9939609 (in the GOLDN) and rs1121980 (in the GOLDN and BPRHS). We found significant interactions between PA and FTO on BMI in the GOLDN but not in the BPRHS. We found a significant interaction between SFA intake and FTO on BMI, which was stronger than that of total fat and was present in both populations (P-interaction = 0.007 in the GOLDN and P-interaction = 0.014 in BPRHS for categorical; and P-interaction = 0.028 in the GOLDN and P interaction = 0.041 in BPRHS for continuous SFA). Thus, homozygous participants for the FTO-risk allele had a higher mean BMI than the other genotypes only when they had a high-SFA intake (above the population mean: 29.7 +/- 0.7 vs. 28.1 +/- 0.5 kg/m2; P = 0.037 in the GOLDN and 33.6. +/- 0.8 vs. 31.2 +/- 0.4 kg/m2; P = 0.006 in BPRHS). No associations with BMI were found at lower SFA intakes. We found no significant interactions with carbohydrate intake. In conclusion, SFA intake modulates the association between FTO and BMI in American populations. PMID- 22049298 TI - Physicians in US Prisons in the Era of Mass Incarceration. AB - The United States leads the world in creating prisoners, incarcerating one in 100 adults and housing 25% of the world's prisoners. Since the 1976, the US Supreme Court ruling that mandated health care for inmates, doctors have been an integral part of the correctional system. Yet conditions within corrections are not infrequently in direct conflict with optimal patient care, particularly for those suffering from mental illness and addiction. In addition to providing and working to improve clinical care for prisoners, physicians have an opportunity and an obligation to advocate for reform in the system of corrections when it conflicts with patient well-being. PMID- 22049297 TI - Genetic variation in stearoyl-CoA desaturase 1 is associated with metabolic syndrome prevalence in Costa Rican adults. AB - Stearoyl-CoA desaturase 1 (SCD1) activity, a key regulator of lipid metabolism, may be associated with the development of metabolic syndrome (MetS). We examined the association of genetic variation in the SCD1 gene with the occurrence of MetS and its five components in a population of Costa Rican adults (n = 2152; mean age, 58 y; range, 18-86 y). Associations of tag single nucleotide polymorphisms (tagSNP) of the SCD1 gene with prevalence of MetS and its five components were analyzed by use of log-Poisson models with robust variance estimates and linear regression models, respectively. The likelihood ratio was used to test potential gene-fatty acid interactive effects with adipose tissue alpha-linolenic acid. One tagSNP (rs1502593) was significantly associated with an increased prevalence of MetS in the total study sample. Compared with the common homozygous CC genotype, the CT and TT genotypes for rs1502593 were associated with higher prevalence ratios (PR) of MetS for CT vs. CC: [PR = 1.22 (95% CI = 1.03, 1.44)] and for TT vs. CC [PR = 1.24 (95% CI = 1.01, 1.52)]. Among women, we observed borderline positive associations between systolic blood pressure and fasting blood sugar levels and rs1502593 (P = 0.05 and 0.06). Compared to the common haplotype (frequency >= 5%) with no minor alleles of SCD1 tagSNP, the other two observed common haplotypes carrying the rs1502593 minor allele were significantly associated with elevated prevalence of MetS. No gene-fatty acid interactive effects were observed. Our results suggest that genetic variation in the SCD1 gene may play a role in the development of MetS. PMID- 22049299 TI - Why we still don't understand the depressed brain - Not going beyond snapshots. AB - Although remarkable progress has been made in the search for the brain correlates of depression with neuroimaging methods, we still find a heterogeneity of results and lack of consensus. This short commentary proposes a theoretical reason for this situation linking it to the methods of conducting neuroimaging studies of depression and the ways to interpret findings. If we only take one snapshot of the "depressed brain", the brain activity is presumably the result of four interacting components: neural predispositions, depressogenic pathology, changes caused by (chronic) depression, and compensatory brain mechanisms. The four components will be discussed briefly along with arguments why confusion of them might confuse our view of the brain in depression. After a short presentation of promising new longitudinal studies, this commentary gives first hints how we could go beyond snapshots to better understand the brain in depression. PMID- 22049300 TI - Integration and health-related quality of life of undergraduate medical students with migration backgrounds - Results of a survey. AB - OBJECTIVE: Most medical faculties in Germany are still lacking differentiated counseling programmes for specific target groups. The purpose of the present study was to determine the quality of life and integration of students with migration backgrounds and their interests in counseling programmes. METHODS: Data was collected at the University Medical Center Hamburg-Eppendorf in Germany. Participants were students of the undergraduate medical course; n=890 (89.3%) students without migration backgrounds were compared to n=107 (10.7%) students with an existing migration background. RESULTS: The results showed that medical students with migration backgrounds reported lower scores for health-related quality of life compared to students without a migration background. They felt less accepted and supported by their fellow students and had fewer contacts with other students. Medical students with migration backgrounds were characterised by a higher interest in the implementation of a counseling programme (Z=-3.420; p=.001). CONCLUSIONS: In summary, medical students with migration backgrounds were identified as a group with an increased need for a specific counseling service. Lower scores of mental health and feelings of inferior integration set the necessity for early counseling and intervention needs. PMID- 22049301 TI - Hypervalent iodine(III)-induced methylene acetoxylation of 3-oxo-N-substituted butanamides. AB - 1-Carbamoyl-2-oxopropyl acetate derivatives were synthesized through an acetoxylation process to methylene with the aid of (diacetoxyiodo)benzene (DIB) as the oxidant. Not only mild reaction conditions, but also excellent yields and good substrate scope make the present protocol potentially useful in organic synthesis. PMID- 22049302 TI - Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions. AB - The multistep flow synthesis of vinyl azides and their application in the synthesis of vinyltriazoles is reported. The synthesis relies on a stable polymer bound equivalent of iodine azide that serves to carry out 1,2-functionalization of alkenes in a telescope flow protocol. The intermediate 2-iodo azides are subjected to a DBU-mediated polymer-supported elimination step yielding vinyl azides in good yield. The third step involves the formation of vinyl triazoles by a copper-catalyzed Huisgen-"click" cycloaddition. The required heat is generated by electromagnetic induction based on copper. Copper serves both as heatable as well as catalytically active packed-bed material inside the flow reactor. PMID- 22049303 TI - Association of contrast sensitivity with LogMAR visual acuity and glycosylated hemoglobin in non-insulin dependent diabetes mellitus. AB - A tertiary care center-based prospective case-control study was undertaken to evaluate the association of contrast sensitivity with LogMAR visual acuity and glycosylated hemoglobin (HbA1c) in 205 cases of non-insulin dependent diabetes mellitus and 115 controls. LogMAR visual acuity and contrast sensitivity were scored using ETDRS and Pelli-Robson charts, respectively. Bivariate correlation between contrast sensitivity and LogMAR visual acuity showed significant inverse correlation in cases without retinopathy (r = -0.466) and with non-proliferative retinopathy (r = -0.307). In a multivariate model, on applying linear regression analysis, LogMAR visual acuity (p < 0.001) and HbA1c (p = 0.002) had significant association with contrast sensitivity. Significant difference in contrast sensitivity was not observed between cases without diabetic retinopathy and with non-proliferative diabetic retinopathy, implying no association with retinal microvascular changes. Contrast sensitivity dysfunction observed in diabetes mellitus results from changes in retinal function secondary to alteration in carbohydrate metabolism depicted in glycosylated hemoglobin. PMID- 22049304 TI - A dual micro-CT system for small animal imaging. AB - Micro-CT is a non-invasive imaging modality usually used to assess morphology in small animals. In our previous work, we have demonstrated that functional micro CT imaging is also possible. This paper describes a dual micro-CT system with two fixed x-ray/detectors developed to address such challenging tasks as cardiac or perfusion studies in small animals. A two-tube/detector system ensures simultaneous acquisition of two projections, thus reducing scanning time and the number of contrast injections in perfusion studies by a factor of two. The system is integrated with software developed in-house for cardio-respiratory monitoring and gating. The sampling geometry was optimized for 88 microns in such a way that the geometric blur of the focal spot matches the Nyquist sample at the detector. A geometric calibration procedure allows one to combine projection data from the two chains into a single reconstructed volume. Image quality was measured in terms of spatial resolution, uniformity, noise, and linearity. The modulation transfer function (MTF) at 10% is 3.4 lp/mm for single detector reconstructions and 2.3 lp/mm for dual tube/detector reconstructions. We attribute this loss in spatial resolution to the compounding of slight errors in the separate single chain calibrations. The dual micro-CT system is currently used in studies for morphological and functional imaging of both rats and mice. PMID- 22049305 TI - Cytoskeletal dynamics: concepts in measles virus replication and immunomodulation. AB - In common with most viruses, measles virus (MV) relies on the integrity of the cytoskeleton of its host cells both with regard to efficient replication in these cells, but also retention of their motility which favors viral dissemination. It is, however, the surface interaction of the viral glycoprotein (gp) complex with receptors present on lymphocytes and dendritic cells (DCs), that signals effective initiation of host cell cytoskeletal dynamics. For DCs, these may act to regulate processes as diverse as viral uptake and sorting, but also the ability of these cells to successfully establish and maintain functional immune synapses (IS) with T cells. In T cells, MV signaling causes actin cytoskeletal paralysis associated with a loss of polarization, adhesion and motility, which has been linked to activation of sphingomyelinases and subsequent accumulation of membrane ceramides. MV modulation of both DC and T cell cytoskeletal dynamics may be important for the understanding of MV immunosuppression at the cellular level. PMID- 22049306 TI - What has the study of the K3 and K5 viral ubiquitin E3 ligases taught us about ubiquitin-mediated receptor regulation? AB - Cells communicate with each other and the outside world through surface receptors, which need to be tightly regulated to prevent both overstimulation and receptor desensitization. Understanding the processes involved in the homeostatic control of cell surface receptors is essential, but we are not alone in trying to regulate these receptors. Viruses, as the ultimate host pathogens, have co evolved over millions of years and have both pirated and adapted host genes to enable viral pathogenesis. K3 and K5 (also known as MIR1 and MIR2) are viral ubiquitin E3 ligases from Kaposi's Sarcoma Associated Herpesvirus (KSHV) which decrease expression of a number of cell surface receptors and have been used to interrogate cellular processes and improve our understanding of ubiquitin mediated receptor endocytosis and degradation. In this review, we summarize what has been learned from the study of these viral genes and emphasize their role in elucidating the complexity of ubiquitin in receptor regulation. PMID- 22049309 TI - A case of circumferential multi-vessel coronary intramural hematoma in a post menopausal woman. AB - Spontaneous coronary dissections are a well described entity which are often difficult to treat. Intramural hematoma is one type of coronary dissection. Previous case reports have described the treatment for angiographically visible dissection. We describe the first report of diffuse intramural hematoma visualized only on intravascular ultrasound with no angiographically obvious evidence of dissection treated with multivessel drug eluting stenting. This case highlights the importance of a high level of suspicion and atypical presentations of coronary dissection, and the use of multimodality imaging with intravascular ultrasound and computerized tomography for both diagnosis and therapy. PMID- 22049308 TI - Flavivirus cell entry and membrane fusion. AB - Flaviviruses, such as dengue virus and West Nile virus, are enveloped viruses that infect cells through receptor-mediated endocytosis and fusion from within acidic endosomes. The cell entry process of flaviviruses is mediated by the viral E glycoprotein. This short review will address recent advances in the understanding of flavivirus cell entry with specific emphasis on the recent study of Zaitseva and coworkers, indicating that anionic lipids might play a crucial role in the fusion process of dengue virus [1]. PMID- 22049310 TI - Isolated right ventricular failure in hyperthyroidism: a clinical dilemma. AB - We present a unique case of a 42-year-old gentleman with newly diagnosed Graves' disease and isolated right ventricular failure. Extensive evaluation to include echocardiogram and cardiac catheterization were negative for significant pulmonary hypertension or coronary artery disease as potential etiologies. Hyperthyroid induced vasospasm is a rare but reported clinical entity that serves to be a clinical and diagnostic dilemma. PMID- 22049307 TI - The inside out of lentiviral vectors. AB - Lentiviruses induce a wide variety of pathologies in different animal species. A common feature of the replicative cycle of these viruses is their ability to target non-dividing cells, a property that constitutes an extremely attractive asset in gene therapy. In this review, we shall describe the main basic aspects of the virology of lentiviruses that were exploited to obtain efficient gene transfer vectors. In addition, we shall discuss some of the hurdles that oppose the efficient genetic modification mediated by lentiviral vectors and the strategies that are being developed to circumvent them. PMID- 22049312 TI - Platypnea-orthodeoxia due to osteoporosis and severe kyphosis: a rare cause for dyspnea and hypoxemia. AB - Platypnea orthodeoxia is a rare disorder characterized by dyspnea and arterial desaturation, exacerbated by the upright position and relieved when the subject is recumbent. We report the case of a 79-year old woman admitted to hospital with dyspnea who was thought to have restrictive ventilatory impairment due to osteoporosis and severe kyphosis. Interestingly, the dyspnea was aggravated in the upright position, whereas the symptoms improved in the supine position. Arterial blood gas analysis confirmed orthodeoxia. The lung function test showed only a mild obstructive and restrictive ventilation disorder. Echocardiography revealed a patent foramen ovale and an aneurysm of the atrial septum protruding into the left atrium, despite normal right atrial pressure. Transesophageal echocardiography showed a prominent Eustachian valve guiding a blood flow from the inferior vena cava directly onto the atrial septum, thereby pushing open the patent foramen ovale. Contrast-enhanced echocardiography confirmed a spontaneous right-to-left shunt through the patent foramen ovale. It was assumed that the platypnea-orthodeoxia was caused by a prominent Eustachian valve redirected to the patent foramen ovale as a result of severe osteoporosis with subsequent thoracic kyphosis and a change in the position of the entire heart. The patient underwent permanent transcatheter closure of the patent foramen ovale after hemodynamic assessment had confirmed a significant right-to-left shunt through it. After the procedure the arterial oxygen pressure increased significantly in the upright position and dyspnea improved. PMID- 22049311 TI - Mild hyperkalemia and low eGFR a tedious recipe for cardiac disaster in the elderly: an unusual reversible cause of syncope and heart block. AB - Hyperkalemia affects the myocardial tissue producing electrocardiographic abnormalities, such as prolongation of the P-R interval, tall peaked T waves, a reduction in the amplitude and an increase in the duration of P wave, and atrial and ventricular arrhythmias, including variable degree heart blocks. Elderly patients are particularly predisposed to developing hyperkalemia and the associated abnormalities due to an age-related reduction in glomerular filtration rate and pre-existing medical problems. Therefore, the impact of aging on potassium homeostasis must be taken into consideration, and preventive measures, such as early recognition of possible hyperkalemia in the geriatric population treated with certain medications or supplements must be investigated. The threshold for cardiac arrhythmias in the elderly can be lower than the general population. We report 3 unusual cases of mild hyperkalemia in elderly patients presenting with hypotension, syncope and variable degree heart blocks which resolved spontaneously with the correction of hyperkalemia. PMID- 22049313 TI - Large patent ductus arteriosus in an adult complicated by pulmonary endarteritis and embolic lung abscess. AB - Patent ductus arteriosus in the adult is an extremely rare clinical phenomenon. We report the case of a 34-year old man who developed pulmonary endarteritis and subsequent embolic lung abscess secondary to a large patent ductus arteriosus. This brief report also provides an overview of the natural history, potential complications, optimal therapy, and diagnostic dilemmas associated with this persistent congenital cardiac defect in adults. PMID- 22049314 TI - Are there differences in acute phase inflammation markers regarding the type of heart failure? AB - This study aimed to determine if there are differences in inflammatory markers in the acute phase between systolic heart failure and heart failure with preserved systolic function. One hundred and thirty-one patients with acute heart failure were recruited consecutively. At admission, plasma fibrinogen, C-reactive protein, sialic acid, von Willebrand factor, vascular endothelial growth factor, interleukin-6 and NTproBNP were all evaluated. If the ejection fraction was 45% or over patients were included in the HF-PSF group; the remaining patients were included in the SHF group. The HF-PSF patients were older (72+/-10 vs 63+/-12 years, P<0.001), presented a higher rate of atrial fibrillation (56.1 vs 21.3%, P<0.001), and had a lower rate of hemoglobin (12.2+/-2 vs 13.3+/-2.1 g/dL, P<0.01). No significant differences were observed in the inflammation markers analyzed among SHF and HF-PSF groups. In the acute phase of heart failure there is a marked elevation of inflammatory markers but there are no differences in the inflammatory markers analyzed between the two different types of heart failure. PMID- 22049315 TI - Baroreflex sensitivity differs among same strain Wistar rats from the same laboratory. AB - Previous studies showed that a proportion of normotensive Sprague-Dawley rats spontaneously exhibit lower baroreflex sensitivity. However, investigations have not yet been carried out on Wistar rats. We aimed to compare baroreflex sensitivity among rats from the same strain and the same laboratory. Male Wistar normotensive rats (300-400g) were studied. Cannulas were inserted into the abdominal aortic artery through the right femoral artery to measure mean arterial pressure and heart rate. Baroreflex was calculated as the derivative of the variation of heart rate in function of the mean arterial pressure variation (DeltaHR/DeltaMAP) tested with a depressor dose of sodium nitroprusside (50 ug/kg) and with a pressor dose of phenylephrine (8ug/kg) in the right femoral venous approach through an inserted cannula. We divided the rats into four groups: i) high bradycardic baroreflex, baroreflex gain less than -2 tested with phenylephrine; ii) low bradycardic baroreflex, baroreflex gain between -1 and -2 tested with phenylephrine; iii) high tachycardic baroreflex, baroreflex gain less than -3 tested with sodium nitroprusside; and iv) low tachycardic baroreflex, baroreflex gain between -1 and -3 tested with sodium nitroprusside. Approximately 71% of the rats presented a decrease in bradycardic reflex while around half showed an increase in tachycardic reflex. No significant changes in basal mean arterial pressure and heart rate, tachycardic and bradycardic peak and heart rate range were observed. There was a significant change in baroreflex sensitivity among rats from the same strain and the same laboratory. PMID- 22049317 TI - Health behavior: an interlocking personal and social task. AB - Traditional health behavior models comprise only person-centered motivational components such as personal vulnerability perceptions and specific internal control beliefs. However, such factors as social responsibility, perceived prevalence rates of illnesses, attribution of control to societal agencies, and the motivation to engage oneself for public health concerns are not unrelated to individual health protection. Therefore, an alternative model is proposed, which combines traditional self-centered and social variables. This alternative model was empirically confirmed in a questionnaire study exemplified by cancer preventive activities (N = 558), which embraced personal cancer prevention as well as efforts to reduce the cancer prevalence within the general population. The readiness to engage in personal cancer preventive measures appeared to be closely related to the readiness to engage oneself for public health programs. The motivational predictors of both categories of activities had significant overlap. Implications for model building and intervention strategies to promote individual as well as public health behavior are discussed. PMID- 22049318 TI - Sociodemographic Factors, Smoking and Common Mental Disorder in the Renfrew and Paisley (MIDSPAN) Study. AB - The relationships between common mental disorder measured by the General Health Questionnaire and sociodemographic variables and cigarette smoking were examined from baseline data in a community study of 15,406 men and women, aged between 45 and 64 years from two towns close to Glasgow. Between 1972 and 1976 all those respondents from Renfrew and Paisley between the ages of 45 and 64 years who met the residency criteria were invited to attend community clinics, where a clinical examination was carried out and the General Health Questionnaire was completed by 3783 (53.6 percent) men, and 4683 (56.1 percent) women. Women had a higher risk of disorder than men did. More women (20.3 percent) than men (15.4 percent) were possible cases of common mental disorder. Women showed a decrease in disorder with age but no apparent trend in men was observed. Marital status was significantly associated with disorder, with the widowed and separated showing especially high rates of psychiatric disorder. Married men, in contrast to married women, had relatively low levels of psychiatric disorder. Both social class and level of deprivation of the area were associated with psychiatric disorder. For both men and women there was a trend in disorder associated with social class; men in social class V had twice the level of psychiatric disorder compared to those in social class II. For women there was a shallow gradient showing higher levels of disorder with lower social class. Smoking habits were also related to psychiatric disorder; never- and exsmokers had relatively low rates of psychiatric disorder whereas, among current smokers, risk of psychiatric disorder, increased with the number of cigarettes smoked, though only for women. PMID- 22049316 TI - ERalpha-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. AB - Most estrogen receptor alpha (ER)-positive breast cancers initially respond to antiestrogens, but many eventually become estrogen-independent and recur. We identified an estrogen-independent role for ER and the CDK4/Rb/E2F transcriptional axis in the hormone-independent growth of breast cancer cells. ER downregulation with fulvestrant or small interfering RNA (siRNA) inhibited estrogen-independent growth. Chromatin immunoprecipitation identified ER genomic binding activity in estrogen-deprived cells and primary breast tumors treated with aromatase inhibitors. Gene expression profiling revealed an estrogen independent, ER/E2F-directed transcriptional program. An E2F activation gene signature correlated with a lesser response to aromatase inhibitors in patients' tumors. siRNA screening showed that CDK4, an activator of E2F, is required for estrogen-independent cell growth. Long-term estrogen-deprived cells hyperactivate phosphatidylinositol 3-kinase (PI3K) independently of ER/E2F. Fulvestrant combined with the pan-PI3K inhibitor BKM120 induced regression of ER(+) xenografts. These data support further development of ER downregulators and CDK4 inhibitors, and their combination with PI3K inhibitors for treatment of antiestrogen-resistant breast cancers. PMID- 22049319 TI - Mediators of Increased Physical Activity and Change in Subjective Well-being: Results from the Activity Counseling Trial (ACT). AB - The purpose of this study was to examine whether change in satisfaction with physical function (SF), satisfaction with physical appearance (SA), and self efficacy (SE) mediate the effects that increased physical activity has on change in subjective well-being (SWB). Participants in this investigation consisted of 854 men (n = 471) and women (n = 383) who took part in the Activity Counseling Trial (ACT). ACT was a 24-month multicenter, randomized controlled trial to evaluate the effectiveness of interventions to promote physical activity in the primary care setting. Participants were assigned to one of three treatments: standard care control, staff-assisted intervention, or staff-counseling intervention. Results revealed that, irrespective of treatment arm, change in physical activity was related to change in SBW and to change in all mediators of interest. A statistical test of mediation revealed that the influence of change in physical activity on SWB was due to change in all three mediators with change in SF making the greatest contribution to the model. PMID- 22049320 TI - Proximal and Distal Predictors of AIDS Risk Behaviors among Inner-city African American and European American Women. AB - AIDS risk behavior and attitudes towards safer sex were studied in a sample of 666 African American and 626 European American women. Condom use, AIDS-related knowledge, risk perception, self-efficacy beliefs, attitudes and perceived partner attitudes, and an assertive coping style were analyzed with regard to mean differences and predictive power in both ethnic groups. Compared to European American women, African American women had less knowledge and lower self-efficacy beliefs towards safer sex behavior, but they perceived themselves to be at more risk and reported greater condom use. Further, ethnicity was found to moderate the effects of the psychological predictors on safer sex behavior. This moderator effect was tested using a structural equation modeling design. In both groups, risk perception was the strongest predictor of condom use. Among African American women, social-cognitive barriers (e.g. low self-efficacy beliefs, negative attitude towards condom use) worked as a second predictor and mediator of the effects of risk perception on condom use. In contrast, among European American women, social-cognitive factors had no effect on condom use. In general, prediction of safer sex behavior was stronger among African American women. PMID- 22049321 TI - Do Patients Want Control over their Own Health Care? A Review of Measures, Findings, and Research Issues. AB - Across a wide variety of medical settings, patients report that they want detailed information about their condition and their treatment whereas stated desire for input into decision making is skewed more in the direction of physician-only or at least collaborative decision-making. These results, along with the contextual and individual difference factors associated with increased willingness to relinquish control (lower educational level, more serious illness, increasing age), indicate that patients want to assume control if they feel it will be beneficial to them to do so. The findings, however, are based largely on the relationship of patients' mean scores to arbitrarily determined scale midpoints on measures with little or no criterion-related validity. These measures also show insufficient overlap with better validated measures of desire for health care control, which indicate more normally distributed scores and a broader range of individual differences among respondents. Findings are discussed in terms of the need for further research on the structure (dimensionality) and stability of the construct desire for health care control and issues involved in conducting needed criterion-related validational work. PMID- 22049322 TI - Overcoming perceived barriers to employment among people with arthritis. AB - Work disability is a major problem for people with arthritis. The INTO WORK Personal Development (IWPD) programme aims to prevent work disability by addressing the internal and external barriers faced by people with arthritis seeking to fulfil their employment potential. The effectiveness of the programme was examined in a pretest-post-test study with an intervention group (n = 37) and a comparison control group (n = 42). Data were collected through self administered questionnaires and focus groups. Significant decreases on anxiety (p = .0002), depression (p = .009) and negative mood (p = .029), and significant improvements on positive mood (p = .011), self-esteem (p = .002) and satisfaction with life (p = .010) were found for the intervention group only. The IWPD programme appears to promote self-determination, psychological well-being and strategies for overcoming perceived barriers to employment among people with arthritis. PMID- 22049323 TI - Relaxation training and cortisol secretion in adult asthmatics. AB - Relaxation techniques can lead to symptom reduction and improved pulmonary functioning in asthmatics, although the mechanism is not clear. One possibility is by influencing cortisol secretion, as cortisol is implicated in inflammatory processes and relaxation has been shown to alter cortisol secretion in healthy individuals. This study explored the effect of relaxation training on cortisol levels and cortisol reactivity to stress in asthmatics. Twenty adult asthmatics participated for 21 days in their natural environment, and received relaxation training halfway through the study. Cortisol was assessed from saliva five times per day for three weeks. Relaxation training was successful, but did not lead to the hypothesized reduction in overall cortisol levels. Participants using corticosteroid medication showed increases in cortisol after relaxation, whereas those not using corticosteroids showed decreases in cortisol (p< .05). Relaxation altered the cortisol reactivity to stress (p= .007); before relaxation training cortisol levels increased after a stressor, whereas following relaxation training cortisol levels decreased after a stressor. This study suggests that relaxation training can influence cortisol secretion in asthmatics, but that these effects differ from those observed in healthy individuals and may be influenced by corticosteroid medication use. PMID- 22049324 TI - Blood glucose discrimination training: the role of internal and external cues. AB - The effects of observing internal and external events on blood glucose (BG) discrimination were assessed in eight patients with type 1 diabetes using an intrasubject design. During baseline condition, participants estimated their BG, then measured and recorded it (feedback-only procedure) three times a day. Participants were then divided randomly into two groups. Both were submitted to internal cue (IC) and external cue (EC) training conditions in a balanced order, and then both cues were presented together in combined cues (CC) training conditions. Under IC, participants observed and recorded their symptoms before estimating BG. Under EC, they observed and recorded environmental events prior to BG estimation. In CC conditions, participants paid attention to both internal and external cues before the estimate-feedback routine. BG estimation accuracy improved after either IC or EC conditions. When the two types of cues were combined, only two participants improved their BG estimation accuracy. The remainder did not, probably because they had already attained high accuracy levels (ceiling effect). PMID- 22049325 TI - Individualism and immune function: are asthma and allergies partly a function of an overly constricted self? AB - Relations of individualism/collectivism to asthma and allergies were examined in two studies. I proposed that a narrower psychological identity (individualism) might be associated with an overactive immune system. In Study 1, average individualism levels across 15 countries correlated significantly positively (.50) with national asthma rates. Pollution and crowding levels were unrelated to national asthma rates. In Study 2, higher levels of personality individualism were associated with higher numbers of allergies among college students even with some other individual difference factors controlled. Potential mechanisms behind, and potential implications of, these results are described. Some suggestions for further research on this topic are given. PMID- 22049326 TI - Narrative Identities and the Management of Personal Accountability in Talk about ME: A Discursive Psychology Approach to Illness Narrative. AB - This article takes a discursive psychology approach to the analysis of illness narrative. The controversial topic of ME (myalgic encephalomyelitis), otherwise known as chronic fatigue syndrome (CFS), is used as a case study to examine the dilemmatics of illness talk. Using data from an ME narrative, I explore the complex and subtle discursive work performed by participants to show how attributional stories and identity formulations are linked together in a narrative that works to construct ME as a physical disease while countering potential accusations of malingering or psychological vulnerability. In working to counter such explanations, sufferers paradoxically implicate themselves in an interpretation of their illness as self-inflicted through overwork and mismanagement. In previous research, tales of frenetic lifestyles prior to the onset of ME have provided analysts (and journalists) with grounds for constructing their own attributional stories in the form of 'opt-out' or 'burnout' theories of ME/CFS. An ethnomethodologically informed discursive psychology provides a non-cognitivist approach to analysis which looks in detail at how sufferers themselves make sense of ME as a practical activity and how their identities are constructed as part of that process. PMID- 22049328 TI - Health and work: critical perspectives. PMID- 22049327 TI - Qualitative health psychology: theories and methods. PMID- 22049329 TI - Material discourses of health and illness. PMID- 22049330 TI - A late phase of LTD in cultured cerebellar Purkinje cells requires persistent dynamin-mediated endocytosis. AB - Long-term synaptic depression (LTD) of cerebellar parallel fiber-Purkinje cell synapses is a form of use-dependent synaptic plasticity that may be studied in cell culture. One form of LTD is induced postsynaptically through an mGlu1/Ca influx/protein kinase Calpha (PKCalpha) cascade, and its initial expression requires phosphorylation of ser-880 in the COOH-terminal PDZ-ligand region of GluA2 and consequent binding of PICK1. This triggers postsynaptic clathrin/dynamin-mediated endocytosis of GluA2-containing surface AMPA receptors. Cerebellar LTD also has a late phase beginning 45-60 min after induction that is blocked by transcription or translation inhibitors. Here, I have sought to determine the expression mechanism of this late phase of LTD by applying various drugs and peptides after the late phase has been established. Neither bath application of mGluR1 antagonists (JNJ-16259685, LY-456236) nor the PKC inhibitor GF-109203X starting 60-70 min after LTD induction attenuated the late phase. Similarly, achieving the whole cell configuration with a second pipette loaded with the peptide PKC inhibitor PKC(19-36) starting 60 min postinduction also failed to alter the late phase. Late internal perfusion with peptides designed to disrupt PICK1-GLUA2 interaction or PICK1 dimerization failed to impact late phase LTD expression. However, late internal perfusion with two different blockers of dynamin, the drug dynasore and a dynamin inhibitory peptide (QVPSRPNRAP), produced rapid and complete reversal of cerebellar LTD expression. These findings suggest that the protein synthesis-dependent late phase of LTD requires persistent dynamin-mediated endocytosis, but not persistent PICK1-GluA2 binding nor persistent activation of the upstream mGluR1/PKCalpha signaling cascade. PMID- 22049331 TI - Does a pitch center exist in auditory cortex? AB - Pitch perception is an important component of hearing, allowing us to appreciate melodies and harmonies as well as recognize prosodic cues in speech. Multiple studies over the last decade have suggested that pitch is represented by a pitch processing center in auditory cortex. However, recent data (Barker D, Plack CJ, Hall DA. Cereb Cortex. In press; Hall DA, Plack CJ. Cereb Cortex 19: 576-585, 2009) now challenge these previous claims of a human "pitch center." PMID- 22049332 TI - Cortical entrainment of human hypoglossal motor unit activities. AB - Output from the primary motor cortex contains oscillations that can have frequency-specific effects on the firing of motoneurons (MNs). Whereas much is known about the effects of oscillatory cortical drive on the output of spinal MN pools, considerably less is known about the effects on cranial motor nuclei, which govern speech/oromotor control. Here, we investigated cortical input to one such motor pool, the hypoglossal motor nucleus (HMN), which controls muscles of the tongue. We recorded intramuscular genioglossus electromyogram (EMG) and scalp EEG from healthy adult subjects performing a tongue protrusion task. Cortical entrainment of HMN population activity was assessed by measuring coherence between EEG and multiunit EMG activity. In addition, cortical entrainment of individual MN firing activity was assessed by measuring phase locking between single motor unit (SMU) action potentials and EEG oscillations. We found that cortical entrainment of multiunit activity was detectable within the 15- to 40-Hz frequency range but was inconsistent across recordings. By comparison, cortical entrainment of SMU spike timing was reliable within the same frequency range. Furthermore, this effect was found to be intermittent over time. Our study represents an important step in understanding corticomuscular synchronization in the context of human oromotor control and is the first study to document SMU entrainment by cortical oscillations in vivo. PMID- 22049333 TI - Chondroitinase ABC reduces time to muscle reinnervation and improves functional recovery after sciatic nerve transection in rats. AB - Application of chondroitinase ABC (ChABC) to injured peripheral nerves improves axon regeneration, but it is not known whether functional recovery is also improved. Recordings of EMG activity [soleus (Sol) M response and H reflexes] evoked by nerve stimulation and of Sol and tibialis anterior (TA) EMG activity and hindlimb and foot kinematics during slope walking were made to determine whether ChABC treatment of the sciatic nerve at the time of transection improves functional recovery. Recovery of evoked EMG responses began as multiple small responses with a wide range of latencies that eventually coalesced into one or two more distinctive and consistent responses (the putative M response and the putative H reflex) in both groups. Both the initial evoked responses and the time course of their maturation returned sooner in the ChABC group than in the untreated (UT) group. The reinnervated Sol and TA were coactivated during treadmill locomotion during downslope, level, and upslope walking throughout the study period in both UT and ChABC-treated rats. By 10 wk after nerve transection and repair, locomotor activity in Sol, but not TA, had returned to its pretransection pattern. There was an increased reliance on central control of Sol activation across slopes for both groups as interpreted from elevated prestance Sol EMG activity that was no longer modulated with slope. Limb length and orientation during locomotion were similar to those observed prior to nerve injury during upslope walking only in the ChABC-treated rats. Thus treatment of cut nerves with ChABC leads to improvements in functional recovery. PMID- 22049334 TI - Psychophysical measurement of contrast sensitivity in the behaving mouse. AB - To understand how activity in mammalian neural circuits controls behavior, the mouse is a promising model system due to the convergence of genetic, optical, and physiological methods. The ability to control and quantify behavior precisely is also essential for these studies. We developed an operant visual detection paradigm to make visual psychophysical measurements: head-fixed mice make responses by pressing a lever. We designed this task to permit neurophysiological studies of behavior in cerebral cortex, where activity is variable from trial to trial and neurons encode many types of information simultaneously. To study neural responses in the face of this complexity, we trained mice to do a task where they perform hundreds of trials daily and perceptual thresholds can be measured. We used this task to measure both visual acuity and the minimum detectable contrast in behaving mice. We found that the mouse contrast response function is similar in shape to other species. They can detect low-contrast stimuli, with a peak contrast threshold of 2%, equivalent to ~15 degrees eccentric in human vision. Mouse acuity is modest, with an upper limit near 0.5 cycles/ degrees , consistent with prior data. PMID- 22049335 TI - D(2)-like dopamine receptors differentially regulate unitary IPSCs depending on presynaptic GABAergic neuron subtypes in rat nucleus accumbens shell. AB - In the nucleus accumbens (NAc), a medium spiny (MS) neuron receives GABAergic inputs from two major sources: fast-spiking (FS) neurons and other, adjacent MS neurons. These two types of inhibitory synapses are considered to play different roles in output activities, i.e., FS->MS connections suppress output from the NAc whereas MS->MS connections contribute to lateral inhibition. In the present study, we focused on the electrophysiological properties of unitary inhibitory postsynaptic currents (uIPSCs) obtained from MS->MS connections and FS->MS connections and examined the effects of quinpirole, a dopamine D(2)-like receptor agonist, on uIPSCs with multiple whole cell patch-clamp recording. Application of quinpirole (1 MUM) reliably suppressed the amplitude of uIPSCs by 29.6% in MS->MS connections, with increases in paired-pulse ratio and failure rate. The suppressive effects of quinpirole on uIPSCs were mimicked by 1 MUM PD128907, a D(2/3) receptor agonist, whereas quinpirole-induced suppression of uISPCs was blocked by preapplication of 1 MUM sulpiride or 10 MUM nafadotride, both D(2/3) receptor antagonists. On the other hand, quinpirole (1 MUM) had divergent effects on FS->MS connections, i.e., quinpirole increased uIPSC amplitude in 38.1% of FS >MS connections and 23.8% of FS->MS connections were suppressed by quinpirole. Analysis of coefficient of variation in uIPSC amplitude implied the involvement of presynaptic mechanisms in quinpirole-induced effects on uIPSCs. These results suggest that activation of D(2)-like receptors facilitates outputs from MS neurons in the NAc by reducing lateral inhibition during a dormant period of FS neuron activities. PMID- 22049336 TI - Low-frequency oscillations of the neural drive to the muscle are increased with experimental muscle pain. AB - We investigated the influence of nociceptive stimulation on the accuracy of task execution and motor unit spike trains during low-force isometric contractions. Muscle pain was induced by infusion of hypertonic saline into the abductor digiti minimi muscle of 11 healthy men. Intramuscular EMG signals were recorded from the same muscle during four isometric contractions of 60-s duration at 10% of the maximal force [maximal voluntary contraction (MVC)] performed before injection (baseline), after injection of isotonic (control) or hypertonic saline (pain), and 15 min after pain was no longer reported. Each contraction was preceded by three 3-s ramp contractions from 0% to 10% MVC. The low-frequency oscillations of motor unit spike trains were analyzed by the first principal component of the low pass filtered spike trains [first common component (FCC)], which represents the effective neural drive to the muscle. Pain decreased the accuracy of task performance [coefficient of variation (CoV) for force: baseline, 2.8 +/- 1.8%, pain, 3.9 +/- 1.8%; P < 0.05] and reduced motor unit discharge rates [11.6 +/- 2.3 pulses per second (pps) vs. 10.7 +/- 1.7 pps; P < 0.05]. Motor unit recruitment thresholds (2.2 +/- 1.2% MVC vs. 2.4 +/- 1.6% MVC), interspike interval variability (18.4 +/- 4.9% vs. 19.1 +/- 5.4%), strength of motor unit short-term synchronization [common input strength (CIS) 1.02 +/- 0.44 vs. 0.83 +/ 0.22], and strength of common drive (0.47 +/- 0.08 vs. 0.47 +/- 0.06) did not change across conditions. The FCC signal was correlated with force (R = 0.45 +/- 0.06), and the CoV for FCC increased in the painful condition (5.69 +/- 1.29% vs. 7.83 +/- 2.61%; P < 0.05). These results indicate that nociceptive stimulation increased the low-frequency variability in synaptic input to motoneurons. PMID- 22049337 TI - Possible cues driving context-specific adaptation of optocollic reflex in pigeons (Columba livia). AB - Context-specific adaptation (Shelhamer M, Clendaniel R. Neurosci Lett 332: 200 204, 2002) explains that reflexive responses can be maintained with different "calibrations" for different situations (contexts). Which context cues are crucial and how they combine to evoke context-specific adaptation is not fully understood. Gaze stabilization in birds is a nice model with which to tackle that question. Previous data showed that when pigeons (Columba livia) were hung in a harness and subjected to a frontal airstream provoking a flying posture ("flying condition"), the working range of the optokinetic head response [optocollic reflex (OCR)] extended toward higher velocities compared with the "resting condition." The present study was aimed at identifying which context cues are instrumental in recalibrating the OCR. We investigated that question by using vibrating stimuli delivered during the OCR provoked by rotating the visual surroundings at different velocities. The OCR gain increase and the boost of the fast phase velocity observed during the "flying condition" were mimicked by body vibration. On the other hand, the newly emerged relationship between the fast phase and slow-phase velocities in the "flying condition" was mimicked by head vibration. Spinal cord lesion at the lumbosacral level decreased the effects of body vibration, whereas lesions of the lumbosacral apparatus had no effect. Our data suggest a major role of muscular proprioception in the context-specific adaptation of the stabilizing behavior, while the vestibular system could contribute to the context-specific adaptation of the orienting behavior. Participation of an efferent copy of the motor command driving the flight cannot be excluded. PMID- 22049338 TI - Disorder-to-order transition underlies the structural basis for the assembly of a transcriptionally active PGC-1alpha/ERRgamma complex. AB - Peroxisome proliferator activated receptor (PPAR) gamma coactivator-1alpha (PGC 1alpha) is a potent transcriptional coactivator of oxidative metabolism and is induced in response to a variety of environmental cues. It regulates a broad array of target genes by coactivating a whole host of transcription factors. The estrogen-related receptor (ERR) family of nuclear receptors are key PGC-1alpha partners in the regulation of mitochondrial and tissue-specific oxidative metabolic pathways; these receptors also demonstrate strong physical and functional interactions with this coactivator. Here we perform comprehensive biochemical, biophysical, and structural analyses of the complex formed between PGC-1alpha and ERRgamma. PGC-1alpha activation domain (PGC-1alpha(2-220)) is intrinsically disordered with limited secondary and no defined tertiary structure. Complex formation with ERRgamma induces significant changes in the conformational mobility of both partners, highlighted by significant stabilization of the ligand binding domain (ERRgammaLBD) as determined by HDX (hydrogen/deuterium exchange) and an observed disorder-to-order transition in PGC 1alpha(2-220). Small-angle X-ray scattering studies allow for modeling of the solution structure of the activation domain in the absence and presence of ERRgammaLBD, revealing a stable and compact binary complex. These data show that PGC-1alpha(2-220) undergoes a large-scale conformational change when binding to the ERRgammaLBD, leading to substantial compaction of the activation domain. This change results in stable positioning of the N-terminal part of the activation domain of PGC-1alpha, favorable for assembly of an active transcriptional complex. These data also provide structural insight into the versatile coactivation profile of PGC-1alpha and can readily be extended to understand other transcriptional coregulators. PMID- 22049339 TI - Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients. AB - Molecules differentially expressed in blood vessels among organs or between damaged and normal tissues, are attractive therapy targets; however, their identification within the human vasculature is challenging. Here we screened a peptide library in cancer patients to uncover ligand-receptors common or specific to certain vascular beds. Surveying ~2.35 x 10(6) motifs recovered from biopsies yielded a nonrandom distribution, indicating that systemic tissue targeting is feasible. High-throughput analysis by similarity search, protein arrays, and affinity chromatography revealed four native ligand-receptors, three of which were previously unrecognized. Two are shared among multiple tissues (integrin alpha4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white adipose tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases). These findings provide vascular molecular markers for biotechnology and medical applications. PMID- 22049340 TI - Formation of unconventional standing waves at graphene edges by valley mixing and pseudospin rotation. AB - We investigate the roles of the pseudospin and the valley degeneracy in electron scattering at graphene edges. It is found that they are strongly correlated with charge density modulations of short-wavelength oscillations and slowly decaying beat patterns in the electronic density profile. Theoretical analyses using nearest-neighbor tight-binding methods and first-principles density-functional theory calculations agree well with our experimental data from scanning tunneling microscopy. The armchair edge shows almost perfect intervalley scattering with pseudospin invariance regardless of the presence of the hydrogen atom at the edge, whereas the zigzag edge only allows for intravalley scattering with the change in the pseudospin orientation. The effect of structural defects at the graphene edges is also discussed. PMID- 22049341 TI - Nonautonomous regulation of Drosophila midgut stem cell proliferation by the insulin-signaling pathway. AB - Drosophila adult midgut intestinal stem cells (ISCs) maintain tissue homeostasis by producing progeny that replace dying enterocytes and enteroendocrine cells. ISCs adjust their rates of proliferation in response to enterocyte turnover through a positive feedback loop initiated by secreted enterocyte-derived ligands. However, less is known about whether ISC proliferation is affected by growth of the progeny as they differentiate. Here we show that nutrient deprivation and reduced insulin signaling results in production of growth-delayed enterocytes and prolonged contact between ISCs and newly formed daughters. Premature disruption of cell contact between ISCs and their progeny leads to increased ISC proliferation and rescues proliferation defects in insulin receptor mutants and nutrient-deprived animals. These results suggest that ISCs can indirectly sense changes in nutrient and insulin levels through contact with their daughters and reveal a mechanism that could link physiological changes in tissue growth to stem cell proliferation. PMID- 22049342 TI - Schizophrenia susceptibility gene dysbindin regulates glutamatergic and dopaminergic functions via distinctive mechanisms in Drosophila. AB - The dysfunction of multiple neurotransmitter systems is a striking pathophysiological feature of many mental disorders, schizophrenia in particular, but delineating the underlying mechanisms has been challenging. Here we show that manipulation of a single schizophrenia susceptibility gene, dysbindin, is capable of regulating both glutamatergic and dopaminergic functions through two independent mechanisms, consequently leading to two categories of clinically relevant behavioral phenotypes. Dysbindin has been reported to affect glutamatergic and dopaminergic functions as well as a range of clinically relevant behaviors in vertebrates and invertebrates but has been thought to have a mainly neuronal origin. We find that reduced expression of Drosophila dysbindin (Ddysb) in presynaptic neurons significantly suppresses glutamatergic synaptic transmission and that this glutamatergic defect is responsible for impaired memory. However, only the reduced expression of Ddysb in glial cells is the cause of hyperdopaminergic activities that lead to abnormal locomotion and altered mating orientation. This effect is attributable to the altered expression of a dopamine metabolic enzyme, Ebony, in glial cells. Thus, Ddysb regulates glutamatergic transmission through its neuronal function and regulates dopamine metabolism by regulating Ebony expression in glial cells. PMID- 22049343 TI - Alternatively spliced domains interact to regulate BK potassium channel gating. AB - Most human genes contain multiple alternative splice sites believed to extend the complexity and diversity of the proteome. However, little is known about how interactions among alternative exons regulate protein function. We used the Caenorhabditis elegans slo-1 large-conductance calcium and voltage-activated potassium (BK) channel gene, which contains three alternative splice sites (A, B, and C) and encodes at least 12 splice variants, to investigate the functional consequences of alternative splicing. These splice sites enable the insertion of exons encoding part of the regulator of K(+) conductance (RCK)1 Ca(2+) coordination domain (exons A1 and A2) and portions of the RCK1-RCK2 linker (exons B0, B1, B2, C0, and C1). Exons A1 and A2 are used in a mutually exclusive manner and are 67% identical. The other exons can extend the RCK1-RCK2 linker by up to 41 residues. Electrophysiological recordings of all isoforms show that the A1 and A2 exons regulate activation kinetics and Ca(2+) sensitivity, but only if alternate exons are inserted at site B or C. Thus, RCK1 interacts with the RCK1 RCK2 linker, and the effect of exon variation on gating depends on the combination of alternate exons present in each isoform. PMID- 22049346 TI - Getting injured runners back on track. AB - With more people running--and incurring lower extremity injuries--than ever before, you'll have many occasions to use this handy diagnostic and treatment guide. PMID- 22049347 TI - Identifying cognitive impairment during the Annual Wellness Visit: who can you trust? AB - This study found that patients, family members, and even physicians have trouble detecting cognitive impairment. A better bet: routinely administer an objective cognition test. PMID- 22049344 TI - Altered axonal targeting and short-term plasticity in the hippocampus of Disc1 mutant mice. AB - Carefully designed animal models of genetic risk factors are likely to aid our understanding of the pathogenesis of schizophrenia. Here, we study a mouse strain with a truncating lesion in the endogenous Disc1 ortholog designed to model the effects of a schizophrenia-predisposing mutation and offer a detailed account of the consequences that this mutation has on the development and function of a hippocampal circuit. We uncover widespread and cumulative cytoarchitectural alterations in the dentate gyrus during neonatal and adult neurogenesis, which include errors in axonal targeting and are accompanied by changes in short-term plasticity at the mossy fiber/CA3 circuit. We also provide evidence that cAMP levels are elevated as a result of the Disc1 mutation, leading to altered axonal targeting and dendritic growth. The identified structural alterations are, for the most part, not consistent with the growth-promoting and premature maturation effects inferred from previous RNAi-based Disc1 knockdown. Our results provide support to the notion that modest disturbances of neuronal connectivity and accompanying deficits in short-term synaptic dynamics is a general feature of schizophrenia-predisposing mutations. PMID- 22049348 TI - Managing eczema in children--a treatment update. AB - What's the best way to manage pediatric atopic dermatitis? Do alternative remedies work? This evidence-based review--and easy-to-use treatment formula- answers these questions. PMID- 22049349 TI - PURLs: Zinc for the common cold--not if, but when. AB - A new meta-analysis shows that zinc supplementation can reduce the duration and severity of a cold, if it's started early on. PMID- 22049350 TI - PURLs: Ear wax removal: help patients help themselves. AB - Do-it-yourself ear wax removal is safe and simple--and a timesaver for patients as well as physicians. PMID- 22049351 TI - Breast swelling and erythema in a teen. AB - An ED doctor suspected a cat scratch was to blame and prescribed antibiotics. A week later, though, the patient developed dyspnea. PMID- 22049352 TI - Clinical inquiries. What's best for croup? AB - A single dose of corticosteroids is the first-line treatment for croup, resulting in fewer return visits and hospital admissions, shorter lengths of stay in the emergency department (ED) or hospital, and less need for supplemental medication (strength of recommendation [SOR]: A, meta-analysis and randomized controlled trials [RCTs]). A 0.15 mg/kg dose of oral dexamethasone is as effective as larger doses (SOR: B, small RCTs).Nebulized racemic or L-epinephrine reduces severity of symptoms in moderate-to-severe croup (SOR: C, limited-quality disease-oriented evidence).The role of heliox in moderate to severe croup remains uncertain. Studies to date have been inadequate (SOR: C, limited-quality disease-oriented evidence).Humidified air provides no demonstrable benefit in the acute setting (SOR: A, meta-analysis). PMID- 22049353 TI - Clinical inquiries. Which regimen treats vitamin D deficiency most effectively? AB - Several vitamin D replacement regimens are effective. Cumulative dosing may be more important than frequency of dosing (strength of recommendation [SOR]: C, inconsistent results from randomized controlled trials [RCTs] of disease-oriented outcomes).Vitamin D3 (cholecalciferol) may increase serum 25-hydroxy vitamin D (25[OH]D) concentrations more effectively than vitamin D2 (ergocalciferol) (SOR: C, a single RCT of disease-oriented outcomes). PMID- 22049354 TI - Clinical inquiries. Which combination drug therapies are most effective for hypertension? AB - Insufficient evidence exists to determine which specific combinations most effectively decrease cardiovascular morbidity and mortality, although combinations of hypertension medications at lower doses generally reduce cardiovascular outcomes (stroke, coronary heart disease) more than monotherapy (strength of recommendation [SOR]: A, large meta-analyses).The combination of benazepril and amlodipine reduces the composite endpoint of cardiovascular events and deaths more than benazepril plus hydrochlorothiazide with similar rates of adverse effects (SOR: A, randomized controlled trial [RCT]).Combining an angiotensin converting enzyme inhibitor (ACE-I) with a thiazide, beta-blocker, or calcium channel blocker produces side effects similar to monotherapy, as does combining an angiotensin receptor blocker (ARB) with a thiazide or calcium channel blocker (SOR: A, meta-analyses). However, an ACE-I combined with an ARB increases the risk of renal complications and death more than monotherapy (SOR: A, RCT).. PMID- 22049355 TI - Bromocriptine: its place in type 2 diabetes Tx. AB - Patients intolerant of other diabetes medications or requiring minimal A1c reduction may benefit from bromocriptine. PMID- 22049356 TI - Preparation of highly specific anti-zearalenone antibodies by using the cationic protein conjugate and development of an indirect competitive enzyme-linked immunosorbent assay. AB - Although anti-zearalenone (ZEN) antibodies have been widely prepared, these antibodies cross-react with alpha-zearalenol (alpha-ZOL), beta-zearalenol (beta ZOL), zearalanone (ZAN), alpha-zearalanol (alpha-ZAL) and beta-zearalanol (beta ZAL). To overcome this problem and improve the specificity of immunoassays, we produced anti-ZEN antibodies based on a ZEN-cationic protein conjugate. In this study, ZEN was coupled with cationic bovine serum albumin (cBSA) via a Mannich reaction. After BALB/c mice were immunized with ZEN-cBSA, an immunological response was rapidly induced. The titers of the polyclonal antisera and monoclonal antibody were 30,000 and 20,000, respectively. Cross-reactivity (CR) values of the anti-ZEN polyclonal antisera and monoclonal antibody with the 5 analogs were <7% and <2%, respectively. An indirect competitive enzyme-linked immunosorbent assay based on the monoclonal anti-ZEN antibody was established. The recovery rates of ZEN in spiked cereal and feed were in the range of 80%-120% with coefficients of variation <15%. The intra-assay variation and inter-assay variation in assay buffer were both <5%. Therefore, the results demonstrated a feasible approach for preparing highly specific, higher titer and more rapidly induced antibodies against ZEN by using a ZEN-cBSA conjugate as the immunogen instead of currently used immunogens. PMID- 22049357 TI - A resampling-based Markovian model for automated colon cancer diagnosis. AB - In recent years, there has been a great effort in the research of implementing automated diagnostic systems for tissue images. One major challenge in this implementation is to design systems that are robust to image variations. In order to meet this challenge, it is important to learn the systems on a large number of labeled images from a different range of variation. However, acquiring labeled images is quite difficult in this domain, and hence, the labeled training data are typically very limited. Although the issue of having limited labeled data is acknowledged by many researchers, it has rarely been considered in the system design. This paper successfully addresses this issue, introducing a new resampling framework to simulate variations in tissue images. This framework generates multiple sequences from an image for its representation and models them using a Markov process. Working with colon tissue images, our experiments show that this framework increases the generalization capacity of a learner by increasing the size and variation of the training data and improves the classification performance of a given image by combining the decisions obtained on its sequences. PMID- 22049358 TI - An efficient dictionary learning algorithm and its application to 3-D medical image denoising. AB - In this paper, we propose an efficient dictionary learning algorithm for sparse representation of given data and suggest a way to apply this algorithm to 3-D medical image denoising. Our learning approach is composed of two main parts: sparse coding and dictionary updating. On the sparse coding stage, an efficient algorithm named multiple clusters pursuit (MCP) is proposed. The MCP first applies a dictionary structuring strategy to cluster the atoms with high coherence together, and then employs a multiple-selection strategy to select several competitive atoms at each iteration. These two strategies can greatly reduce the computation complexity of the MCP and assist it to obtain better sparse solution. On the dictionary updating stage, the alternating optimization that efficiently approximates the singular value decomposition is introduced. Furthermore, in the 3-D medical image denoising application, a joint 3-D operation is proposed for taking the learning capabilities of the presented algorithm to simultaneously capture the correlations within each slice and correlations across the nearby slices, thereby obtaining better denoising results. The experiments on both synthetically generated data and real 3-D medical images demonstrate that the proposed approach has superior performance compared to some well-known methods. PMID- 22049359 TI - A new adaptive line enhancer based on singular spectrum analysis. AB - Original adaptive line enhancer (ALE) is used for denoising periodic signals from white noise. ALE, however, relies mainly on second order similarity between the signal and its delayed version and is more effective when the signal is narrowband. A new ALE based on singular spectrum analysis (SSA) is proposed here. In this approach in the reconstruction stage of SSA, the eigentriples are adaptively selected (filtered) using the delayed version of the data. Unlike the conventional ALE where (second) order statistics are taken into account, here the full eigen-spectrum of the embedding matrix is exploited. Consequently, the system works for non-Gaussian noise and wideband periodic signals. By performing some experiments on synthetic signals it is demonstrated that the proposed system is very effective for separation of biomedical data, which often have some periodic or quasi-periodic components, such as EMG affected by ECG artefacts. This data are examined here. PMID- 22049360 TI - Investigation of standing-wave formation in a human skull for a clinical prototype of a large-aperture, transcranial MR-guided focused ultrasound (MRgFUS) phased array: an experimental and simulation study. AB - Standing-wave formation in an ex vivo human skull was investigated using a clinical prototype of a 30-cm diameter with 15-cm radius of curvature, low frequency (230 kHz), hemispherical transcranial magnetic resonance-guided focused ultrasound phased array. Experimental and simulation studies were conducted with changing aperture size and f -number configurations of the phased array and qualitatively and quantitatively examined the acoustic pressure variation at the focus due to standing waves. The results demonstrated that the nodes and antinodes of standing wave produced by the small-aperture array were clearly seen at approximately every 3 mm. The effect of the standing wave became more pronounced as the focus was moved closer to skull base. However, a sharp focus was seen for the full array, and there was no such standing-wave pattern in the acoustic plane or near the skull base. This study showed that the fluctuation pressure amplitude would be greatly reduced by using a large-scale, hemispherical phased array with a low f-number. PMID- 22049361 TI - Tongue-rudder: a glossokinetic-potential-based tongue-machine interface. AB - Glossokinetic potentials (GKPs) are electric potential responses generated by tongue movement. In this study, we use these GKPs to automatically detect and estimate tongue positions, and develop a tongue-machine interface. We show that a specific configuration of electrode placement yields discriminative GKPs that vary depending on the direction of the tongue. We develop a linear model to determine the direction of tongue from GKPs, where we seek linear features that are robust to a baseline drift problem by maximizing the ratio of intertask covariance to intersession covariance. We apply our method to the task of wheelchair control, developing a tongue-machine interface for wheelchair control, referred to as tongue-rudder. A teeth clenching detection system, using electromyography, was also implemented in the system in order to assign teeth clenching as the stop command. Experiments on off-line cursor control and online wheelchair control confirm the unique advantages of our method, such as: 1) noninvasiveness, 2) fine controllability, and 3) ability to integrate with other EEG-based interface systems. PMID- 22049362 TI - Group replicator dynamics: a novel group-wise evolutionary approach for sparse brain network detection. AB - Functional magnetic resonance imaging (fMRI) is increasingly used for studying functional integration of the brain. However, large inter-subject variability in functional connectivity, particularly in disease populations, renders detection of representative group networks challenging. In this paper, we propose a novel technique, "group replicator dynamics" (GRD), for detecting sparse functional brain networks that are common across a group of subjects. We extend the replicator dynamics (RD) approach, which we show to be a solution of the nonnegative sparse principal component analysis problem, by integrating group information into each subject's RD process. Our proposed strategy effectively coaxes all subjects' networks to evolve towards the common network of the group. This results in sparse networks comprising the same brain regions across subjects yet with subject-specific weightings of the identified brain regions. Thus, in contrast to traditional averaging approaches, GRD enables inter-subject variability to be modeled, which facilitates statistical group inference. Quantitative validation of GRD on synthetic data demonstrated superior network detection performance over standard methods. When applied to real fMRI data, GRD detected task-specific networks that conform well to prior neuroscience knowledge. PMID- 22049363 TI - Evaluation of three MRI-based anatomical priors for quantitative PET brain imaging. AB - In emission tomography, image reconstruction and therefore also tracer development and diagnosis may benefit from the use of anatomical side information obtained with other imaging modalities in the same subject, as it helps to correct for the partial volume effect. One way to implement this, is to use the anatomical image for defining the a priori distribution in a maximum-a-posteriori (MAP) reconstruction algorithm. In this contribution, we use the PET-SORTEO Monte Carlo simulator to evaluate the quantitative accuracy reached by three different anatomical priors when reconstructing positron emission tomography (PET) brain images, using volumetric magnetic resonance imaging (MRI) to provide the anatomical information. The priors are: 1) a prior especially developed for FDG PET brain imaging, which relies on a segmentation of the MR-image (Baete , 2004); 2) the joint entropy-prior (Nuyts, 2007); 3) a prior that encourages smoothness within a position dependent neighborhood, computed from the MR-image. The latter prior was recently proposed by our group in (Vunckx and Nuyts, 2010), and was based on the prior presented by Bowsher (2004). The two latter priors do not rely on an explicit segmentation, which makes them more generally applicable than a segmentation-based prior. All three priors produced a compromise between noise and bias that was clearly better than that obtained with postsmoothed maximum likelihood expectation maximization (MLEM) or MAP with a relative difference prior. The performance of the joint entropy prior was slightly worse than that of the other two priors. The performance of the segmentation-based prior is quite sensitive to the accuracy of the segmentation. In contrast to the joint entropy prior, the Bowsher-prior is easily tuned and does not suffer from convergence problems. PMID- 22049364 TI - Realistic analytical phantoms for parallel magnetic resonance imaging. AB - The quantitative validation of reconstruction algorithms requires reliable data. Rasterized simulations are popular but they are tainted by an aliasing component that impacts the assessment of the performance of reconstruction. We introduce analytical simulation tools that are suited to parallel magnetic resonance imaging and allow one to build realistic phantoms. The proposed phantoms are composed of ellipses and regions with piecewise-polynomial boundaries, including spline contours, Bezier contours, and polygons. In addition, they take the channel sensitivity into account, for which we investigate two possible models. Our analytical formulations provide well-defined data in both the spatial and k space domains. Our main contribution is the closed-form determination of the Fourier transforms that are involved. Experiments validate the proposed implementation. In a typical parallel magnetic resonance imaging reconstruction experiment, we quantify the bias in the overly optimistic results obtained with rasterized simulations-the inverse-crime situation. We provide a package that implements the different simulations and provide tools to guide the design of realistic phantoms. PMID- 22049365 TI - A rapid method for detection of genetically modified organisms based on magnetic separation and surface-enhanced Raman scattering. AB - In this study, a new method combining magnetic separation (MS) and surface enhanced Raman scattering (SERS) was developed to detect genetically modified organisms (GMOs). An oligonucleotide probe which is specific for 35 S DNA target was immobilized onto gold coated magnetic nanospheres to form oligonucleotide coated nanoparticles. A self assembled monolayer was formed on gold nanorods using 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) and the second probe of the 35 S DNA target was immobilized on the activated nanorod surfaces. Probes on the nanoparticles were hybridized with the target oligonucleotide. Optimization parameters for hybridization were investigated by high performance liquid chromatography. Optimum hybridization parameters were determined as: 4 MUM probe concentration, 20 min immobilization time, 30 min hybridization time, 55 degrees C hybridization temperature, 750 mM buffer salt concentration and pH: 7.4. Quantification of the target concentration was performed via SERS spectra of DTNB on the nanorods. The correlation between the target concentration and the SERS signal was found to be linear within the range of 25-100 nM. The analyses were performed with only one hybridization step in 40 min. Real sample analysis was conducted using Bt-176 maize sample. The results showed that the developed MS SERS assay is capable of detecting GMOs in a rapid and selective manner. PMID- 22049366 TI - Mobility timing for agent communities, a cue for advanced connectionist systems. AB - We introduce a wait-and-chase scheme that models the contact times between moving agents within a connectionist construct. The idea that elementary processors move within a network to get a proper position is borne out both by biological neurons in the brain morphogenesis and by agents within social networks. From the former, we take inspiration to devise a medium-term project for new artificial neural network training procedures where mobile neurons exchange data only when they are close to one another in a proper space (are in contact). From the latter, we accumulate mobility tracks experience. We focus on the preliminary step of characterizing the elapsed time between neuron contacts, which results from a spatial process fitting in the family of random processes with memory, where chasing neurons are stochastically driven by the goal of hitting target neurons. Thus, we add an unprecedented mobility model to the literature in the field, introducing a distribution law of the intercontact times that merges features of both negative exponential and Pareto distribution laws. We give a constructive description and implementation of our model, as well as a short analytical form whose parameters are suitably estimated in terms of confidence intervals from experimental data. Numerical experiments show the model and related inference tools to be sufficiently robust to cope with two main requisites for its exploitation in a neural network: the nonindependence of the observed intercontact times and the feasibility of the model inversion problem to infer suitable mobility parameters. PMID- 22049367 TI - Parallel programmable asynchronous neighborhood mechanism for Kohonen SOM implemented in CMOS technology. AB - We present a new programmable neighborhood mechanism for hardware implemented Kohonen self-organizing maps (SOMs) with three different map topologies realized on a single chip. The proposed circuit comes as a fully parallel and asynchronous architecture. The mechanism is very fast. In a medium sized map with several hundreds neurons implemented in the complementary metal-oxide semiconductor 0.18 MUm technology, all neurons start adapting the weights after no more than 11 ns. The adaptation is then carried out in parallel. This is an evident advantage in comparison with the commonly used software-realized SOMs. The circuit is robust against the process, supply voltage and environment temperature variations. Due to a simple structure, it features low energy consumption of a few pJ per neuron per a single learning pattern. In this paper, we discuss different aspects of hardware realization, such as a suitable selection of the map topology and the initial neighborhood range, as the optimization of these parameters is essential when looking from the circuit complexity point of view. For the optimal values of these parameters, the chip area and the power dissipation can be reduced even by 60% and 80%, respectively, without affecting the quality of learning. PMID- 22049368 TI - Scale- and rotation-invariant local binary pattern using scale-adaptive texton and subuniform-based circular shift. AB - This paper proposes an effective scale- and rotation-invariant local binary pattern (LBP) feature for texture classification. A circular neighboring set of an image pixel is defined as a scale-adaptive texton by taking into account the fundamental local structure property of the pixel. The scale space of a texture image is derived by the Laplacian of the Gaussian and then employed to determine the optimal scale of each pixel reflecting the characteristic length of the corresponding structure and determining the radius of the scale-adaptive texton. Different pixels have different optimal scales, resulting in the scale invariance. Contrary to the traditional LBP features that usually ignore global spatial information, the proposed method also defines subuniform patterns of each uniform pattern to improve the discrimination. For each uniform pattern, the subuniform pattern with the maximum statistical value is defined as the dominant orientation subuniform pattern. It is moved to the first column, and the others are circularly shifted. Experimental results demonstrate a good discrimination capability of the proposed scale- and rotation-invariant LBP in texture classification. Particularly, the LBP based on the scale-adaptive texton is promising to be powerful for texture description and scale-invariant texture classification, and the circular shift subuniform LBP can further improve the performance in the rotation-invariant texture classification. PMID- 22049369 TI - Stochastic subset selection for learning with kernel machines. AB - Kernel machines have gained much popularity in applications of machine learning. Support vector machines (SVMs) are a subset of kernel machines and generalize well for classification, regression, and anomaly detection tasks. The training procedure for traditional SVMs involves solving a quadratic programming (QP) problem. The QP problem scales super linearly in computational effort with the number of training samples and is often used for the offline batch processing of data. Kernel machines operate by retaining a subset of observed data during training. The data vectors contained within this subset are referred to as support vectors (SVs). The work presented in this paper introduces a subset selection method for the use of kernel machines in online, changing environments. Our algorithm works by using a stochastic indexing technique when selecting a subset of SVs when computing the kernel expansion. The work described here is novel because it separates the selection of kernel basis functions from the training algorithm used. The subset selection algorithm presented here can be used in conjunction with any online training technique. It is important for online kernel machines to be computationally efficient due to the real-time requirements of online environments. Our algorithm is an important contribution because it scales linearly with the number of training samples and is compatible with current training techniques. Our algorithm outperforms standard techniques in terms of computational efficiency and provides increased recognition accuracy in our experiments. We provide results from experiments using both simulated and real-world data sets to verify our algorithm. PMID- 22049370 TI - Analysis of using interpulse intervals to generate 128-bit biometric random binary sequences for securing wireless body sensor networks. AB - Wireless body sensor network (WBSN), a key building block for m-Health, demands extremely stringent resource constraints and thus lightweight security methods are preferred. To minimize resource consumption, utilizing information already available to a WBSN, particularly common to different sensor nodes of a WBSN, for security purposes becomes an attractive solution. In this paper, we tested the randomness and distinctiveness of the 128-bit biometric binary sequences (BSs) generated from interpulse intervals (IPIs) of 20 healthy subjects as well as 30 patients suffered from myocardial infarction and 34 subjects with other cardiovascular diseases. The encoding time of a biometric BS on a WBSN node is on average 23 ms and memory occupation is 204 bytes for any given IPI sequence. The results from five U.S. National Institute of Standards and Technology statistical tests suggest that random biometric BSs can be generated from both healthy subjects and cardiovascular patients and can potentially be used as authentication identifiers for securing WBSNs. Ultimately, it is preferred that these biometric BSs can be used as encryption keys such that key distribution over the WBSN can be avoided. PMID- 22049371 TI - SparkMed: a framework for dynamic integration of multimedia medical data into distributed m-Health systems. AB - With the advent of 4G and other long-term evolution (LTE) wireless networks, the traditional boundaries of patient record propagation are diminishing as networking technologies extend the reach of hospital infrastructure and provide on-demand mobile access to medical multimedia data. However, due to legacy and proprietary software, storage and decommissioning costs, and the price of centralization and redevelopment, it remains complex, expensive, and often unfeasible for hospitals to deploy their infrastructure for online and mobile use. This paper proposes the SparkMed data integration framework for mobile healthcare (m-Health), which significantly benefits from the enhanced network capabilities of LTE wireless technologies, by enabling a wide range of heterogeneous medical software and database systems (such as the picture archiving and communication systems, hospital information system, and reporting systems) to be dynamically integrated into a cloud-like peer-to-peer multimedia data store. Our framework allows medical data applications to share data with mobile hosts over a wireless network (such as WiFi and 3G), by binding to existing software systems and deploying them as m-Health applications. SparkMed integrates techniques from multimedia streaming, rich Internet applications (RIA), and remote procedure call (RPC) frameworks to construct a Self-managing, Pervasive Automated netwoRK for Medical Enterprise Data (SparkMed). Further, it is resilient to failure, and able to use mobile and handheld devices to maintain its network, even in the absence of dedicated server devices. We have developed a prototype of the SparkMed framework for evaluation on a radiological workflow simulation, which uses SparkMed to deploy a radiological image viewer as an m Health application for telemedical use by radiologists and stakeholders. We have evaluated our prototype using ten devices over WiFi and 3G, verifying that our framework meets its two main objectives: 1) interactive delivery of medical multimedia data to mobile devices; and 2) attaching to non-networked medical software processes without significantly impacting their performance. Consistent response times of under 500 ms and graphical frame rates of over 5 frames per second were observed under intended usage conditions. Further, overhead measurements displayed linear scalability and low resource requirements. PMID- 22049373 TI - Developing a dynamic model of treatment perceptions. AB - A description of factors influencing perceptions of nonpharmacological treatment was derived inductively from interviews with people receiving chiropractic treatment for back pain, using grounded theory analysis. A theoretical model linking these factors was constructed, and was tested using interview data from a longitudinal study of people undertaking exercise therapy for dizziness. The model highlights the potential for reciprocal interactions between abstract beliefs relevant to illness and treatment and concrete experiences of therapy, and for interactions between perceptions of symptom change and of therapist competence. Therapist communication may modify abstract illness/treatment models and symptom perceptions, thus mediating effects of concordance on adherence and placebo effects. PMID- 22049372 TI - Air quality and exercise-related health benefits from reduced car travel in the midwestern United States. AB - BACKGROUND: Automobile exhaust contains precursors to ozone and fine particulate matter (PM <= 2.5 um in aerodynamic diameter; PM2.5), posing health risks. Dependency on car commuting also reduces physical fitness opportunities. OBJECTIVE: In this study we sought to quantify benefits from reducing automobile usage for short urban and suburban trips. METHODS: We simulated census-tract level changes in hourly pollutant concentrations from the elimination of automobile round trips <= 8 km in 11 metropolitan areas in the upper midwestern United States using the Community Multiscale Air Quality (CMAQ) model. Next, we estimated annual changes in health outcomes and monetary costs expected from pollution changes using the U.S. Environmental Protection Agency Benefits Mapping Analysis Program (BenMAP). In addition, we used the World Health Organization Health Economic Assessment Tool (HEAT) to calculate benefits of increased physical activity if 50% of short trips were made by bicycle. RESULTS: We estimate that, by eliminating these short automobile trips, annual average urban PM2.5 would decline by 0.1 ug/m3 and that summer ozone (O3) would increase slightly in cities but decline regionally, resulting in net health benefits of $4.94 billion/year [95% confidence interval (CI): $0.2 billion, $13.5 billion), with 25% of PM2.5 and most O3 benefits to populations outside metropolitan areas. Across the study region of approximately 31.3 million people and 37,000 total square miles, mortality would decline by approximately 1,295 deaths/year (95% CI: 912, 1,636) because of improved air quality and increased exercise. Making 50% of short trips by bicycle would yield savings of approximately $3.8 billion/year from avoided mortality and reduced health care costs (95% CI: $2.7 billion, $5.0 billion]. We estimate that the combined benefits of improved air quality and physical fitness would exceed $8 billion/year. CONCLUSION: Our findings suggest that significant health and economic benefits are possible if bicycling replaces short car trips. Less dependence on automobiles in urban areas would also improve health in downwind rural settings. PMID- 22049374 TI - Associations between attachment representations and health behaviors in late adolescence. AB - In this study, we tested the associations among attachment ratings and health behaviors by relationship status. For individuals in relationships, attachment security was associated positively with health promotion and quality sleep and negatively with risk behaviors; fearfulness was associated positively with risk behaviors. With the exception of sleep behaviors, associations with security and fearfulness were reversed for single participants. Associations between dismissingness and quality of sleep support the proposal that individuals who deny or dismiss their attachment needs may experience physical symptoms of distress that affect their health. Future work exploring the benefits of security when coping with illness or lifestyle change is discussed. PMID- 22049375 TI - Components of the Anger-hostility Complex as Risk Factors for Coronary Artery Disease Severity: A Multi-measure Study. AB - Different forms of anger and hostility have been implicated in the pathogenesis of coronary artery disease (CAD), though previous research has not measured all of these in one sample. To assess their relative predictive utility, a multi measure study was undertaken of three adult outpatient groups: 97 men identified angiographically with stenosed coronary arteries; 28 men with valvular heart disorders in the absence of CAD; and 28 men attending a fracture clinic with no CAD present. Questionnaires measured: anger expression; anger experience; cynical hostility; 'Ho' hostility; neurotic hostility; neurotic disagreeableness; resentment; and suspiciousness. The pre-eminent anger-hostility correlate of CAD was found to be expressed anger, with years as a smoker and age also being independently related to disease severity. Thus, seven of these anger/hostility variables do not warrant similar attention as anger expression in CAD aetiology. Further research should identify coronary toxic components of anger expression and of socio-occupational environments that afford or constrain their occurrence. PMID- 22049376 TI - Reducing skin cancer risk: an intervention based on protection motivation theory. AB - Caucasian college students who intentionally tanned participated in a brief skin cancer intervention based on protection motivation theory (PMT). This intervention targeted skin appearance and consisted of brief lectures, a comprehensive essay, video clips about a young man who died of melanoma, and short discussions. Compared to a waitlist control group, the intervention group showed increases on PMT variables and intentions at post-test. The waitlist group later received the intervention and showed similar increases. Additionally, all but one PMT variable maintained post-test levels at a one-month follow-up. Photographs taken at post-test and at the one-month follow-up were judged by raters blind to the hypothesis. Seventy-two percent of participants were judged to have lighter skin whereas only 16 percent had darker skin. These results provide additional support for theory-based methods for changing maladaptive attitudes and behaviors associated with skin cancer risk. PMID- 22049377 TI - Cancer Patients and their Spouses: Gender and its Effect on Psychological and Social Adjustment. AB - The aim of this research was to examine the effects of gender on the social adjustment and psychological distress experienced by cancer patients and their spouses. A total of 87 patients and spouses participated in the study, with the patients undergoing active medical treatment (chemotherapy, radiation or both) and three months post-diagnosis. Three questionnaires were used to collect data: a personal information one; the Brief Symptom Inventory (BSI), in which stress was examined; and the PAIS-SR, in which psychosocial adjustment to physical illness was examined. Both cancer patients and their spouses reported the same level of psychological distress and difficulties in social adjustment in most areas studied. Patients reported more difficulties in relationships with extended family and in sexual relations than their spouses did. In the area of social environment, spouses reported higher levels of difficulties than patients. Both men and women reported difficulties with social adjustment in most areas studied. Women reported more difficulties with social environment. As for psychological stress, generally men as patients and as spouses reported higher levels of anxiety. As patients, men reported higher levels of paranoia. PMID- 22049379 TI - Radon's Deadly Daughters: Science, Environ-mental Policy, and the Politics of Risk. PMID- 22049378 TI - Article predictors of wellbeing and autonomy before and after geriatric rehabilitation. AB - The aim of this study was to explore changes in the correlational association between predictors (i.e. sociodemographics, subjective health, social support, anxiety and coping) and outcome measures (i.e. subjective wellbeing and autonomy) before and after rehabilitation treatment. The data came from a sample of 90 patients (mean age 78.8 years; 84 percent female; 37 percent stroke, 44 percent fracture, 19 percent other diagnoses), who were assessed before and after rehabilitative treatment. Results revealed that although changes between predictors and outcomes were not prevalent with respect to subjective wellbeing, they were clearly evident with respect to autonomy. Whereas psychological variables, such as state anxiety and behavioural coping, played no predictive role at entry, they became the strongest predictors of autonomy at discharge. PMID- 22049380 TI - Women, Families & HIV/AIDS: A Sociological Perspective on the Epidemic in America. PMID- 22049381 TI - Decolonizing methodologies: research and indigenous people. PMID- 22049382 TI - Psychodynamic perspectives on sickness and health. PMID- 22049383 TI - Early-life exposures and early-onset uterine leiomyomata in black women in the Sister Study. AB - BACKGROUND: Uterine leiomyomata (fibroids) are hormonally responsive tumors, but little is known about risk factors. Early-life exposures may influence uterine development and subsequent response to hormones in adulthood. An earlier analysis of non-Hispanic white women who participated in the Sister Study found associations between several early-life factors and early-onset fibroids. OBJECTIVES: We evaluated associations of early-life and childhood exposures with early-onset fibroids among black women and compared the results with those found among white women. METHODS: We analyzed baseline data from 3,534 black women, 35 59 years of age, in the Sister Study (a nationwide cohort of women who had a sister diagnosed with breast cancer) who self-reported information on early-life and childhood exposures. Early-onset fibroids were assessed based on self-report of a physician diagnosis of fibroids by the age of 30 years (n = 561). We estimated risk ratios (RR) and 95% confidence intervals (CI) from log-binomial regression models. RESULTS: Factors most strongly associated with early-onset fibroids were in utero diethylstilbestrol (DES; RR = 2.02; 95% CI: 1.28, 3.18), maternal prepregnancy diabetes or gestational diabetes (RR = 1.54; 95% CI: 0.95, 2.49), and monozygotic multiple birth (RR = 1.94; 95% CI: 1.26, 2.99). We also found positive associations with having been taller or thinner than peers at the age of 10 years and with early-life factors that included being the firstborn child of a teenage mother, maternal hypertensive disorder, preterm birth, and having been fed soy formula. CONCLUSIONS: With the exception of monozygotic multiple birth and maternal hypertensive disorder, early-life risk factors for early-onset fibroids for black women were similar to those found for white women. However, in contrast to whites, childhood height and weight, but not low socioeconomic status indicators, were associated with early-onset fibroids in blacks. The general consistency of early-life findings for black and white women supports a possible role of early-life factors in fibroid development. PMID- 22049384 TI - [Molecular determinants of response to topoisomerase I inhibitors]. AB - Nuclear topoisomerase I (Top1) is involved in the relaxation of DNA supercoiling and plays a pivotal role in the coordination of essential DNA processes such as transcription, replication, DNA recombination and DNA damage signalling. For all these reasons, Top1 has been an attractive target for the development of anticancer drugs, which poison Top1 by trapping the enzyme on its DNA cleavage sites, which results in irreversible DNA lesions that are responsible for their cytotoxicity. They derive from the natural compound camptothecin and two derivatives are approved in the clinic, topotecan and irinotecan; other compounds such as indolocarbazoles and indenoisoquinolines are in development. However, the efficacy of these drugs is often limited by the problem of resistance, which involves various mechanisms at different steps of drug action, from drug transport and/or metabolism to the signalling and/or repair of the DNA lesions that are generated. A better understanding of these mechanisms is a major concern for the future development of new Top1 inhibitors and the identification of biomarkers that could be used to predict tumour response to these drugs in the clinic and to adapt the treatment to each patient. PMID- 22049385 TI - [Antimetabolites]. AB - Antimetabolites are cytotoxic agents, which have been developed for more than 50 years. Which cancer patient did not receive or will not receive 5-fluorouracil or methotrexate during the evolution his or her disease? Antimetabolites are defined as interfering with the synthesis of the DNA constituents; they are structural analogues, either of purine and pyrimidine bases (or the corresponding nucleosides), or of folate cofactors, which are involved at several steps of purine and pyrimidine biosynthesis. Their first mechanism of action is, therefore, to induce depletion in nucleotides inducing in turn an inhibition of DNA replication. However, some of them are able to get inserted fraudulently into nucleic acids, inducing structural abnormalities leading to cell death by other mechanisms, including DNA breaks. We present in this paper, for the three classes of antimetabolites, both ancient and recent molecules as well as molecules still in clinical trials, without exhaustivity. PMID- 22049386 TI - Psychosomatic Symptoms among Victims of School Bullying. AB - Associations between being a victim of bullying and psychosomatic health have been examined among 856 Norwegian school adolescents aged 13 to 15 years. Multiple logistic and linear regression analyses were applied. Pupils being bullied sometimes or more often during the previous term had significantly higher odds of every psychosomatic symptom except sleeplessness, compared to pupils who reported that they were never exposed to bullying. The highest odds ratio was observed in analysis of feeling low. No significant interactions with gender or age were seen, but the association with irritability, headache and backache tended to be strongest for boys, whereas the association with nervousness and sleeplessness was strongest for girls. Increasing exposure to bullying was associated with a highly significant increase in number of symptoms. The strong and consistent associations with different symptoms and the dose-response relationship suggest a causal relationship. PMID- 22049387 TI - Being a mother and living with asthma: an exploratory analysis of discourse. AB - Although contemporary scholarship on the psychology of women has recognized the significance of motherhood for women, this positioning has received little attention from researchers interested in women and chronic illness. In this article we begin to fill this gap by exploring the complexity of being a mother when women are chronically ill. We focus on mothers with asthma and, adopting a discursive approach, analyze three interviews with asthmatic mothers using discourse analysis to explore how they negotiate their identities. The women were white, Dutch autochthones, who ranged in age from 31 to 60 years. Two were diagnosed with asthma in early childhood and one was diagnosed at age 40. We argue that being a mother is relevant to how women live with asthma. PMID- 22049388 TI - Experiences of Family Caregiving among Older Australian Women. AB - This article uses quantitative and qualitative methods to examine the effects of family caregiving on physical and emotional wellbeing, finances and leisure among a cohort of Australian women aged 70 to 75 years. A total of 11,939 women was examined. Of these, 10 percent (n = 1235) identified themselves as caregivers for frail, ill or disabled family members and 168 made open-ended comments about their caregiving experiences. Unlike other surveys with younger respondents, the data failed to demonstrate any differences in physical health between caregivers and others. Caregivers were, however, significantly more likely to have low levels of emotional wellbeing and to feel stressed, rushed and pressured. Qualitative analysis supported the value of the concept of the 'ethic of care' in understanding the social and individual forces that propel older women into providing family care despite its demonstrably negative effects on their wellbeing. PMID- 22049389 TI - Lay Attitudes toward Genetic Testing for Susceptibility to Inherited Diseases. AB - One of the most important issues facing legal and medical policy makers in the coming years will be whether to employ populationbased testing for genetic markers of inherited diseases. Two hundred and twenty-six randomly selected individuals from Easton, Pennsylvania completed a mail questionnaire that was designed to assess the general public's attitudes toward many of the personal and societal issues surrounding genetic testing for disease susceptibility. Respondents were generally optimistic about the potential benefits of genetic testing, and their attitudes about genetic testing were associated with their personal interest in getting a genetic test. Respondents were more likely to be interested in undergoing genetic testing for disease susceptibility if they might have some control over the targeted disease (i.e. there was a cure) and if the test was highly predictive of their chances of developing the disease. Respondents were wary of granting access to genetic testing results to anyone other than doctors and family members, and they did not want the government, religious leaders, or the courts involved in regulating genetic testing. These results have important implications for psychologists, genetic scientists, bioethicists, and legal scholars who are grappling with the many issues related to population-based genetic testing for inherited diseases. PMID- 22049390 TI - An Exploratory Investigation of the Relationship between Proxy Efficacy, Self efficacy and Exercise Attendance. AB - The purpose of the study was to examine the relationship between perceptions of self-efficacy, proxy efficacy, and exercise class attendance of participants involved in a 10-week structured group fitness program. At week 3, 127 females completed measures of self-efficacy and proxy efficacy and their class attendance was monitored for the subsequent four weeks. Self-efficacy was assessed through measures of exercise, scheduling, and barrier self-efficacy. Proxy efficacy was assessed through a measure of fitness instructor efficacy defined as participants' confidence in their fitness instructors' communication, teaching, and motivating capabilities. Results revealed positive correlations between self efficacy variables and proxy efficacy. Hierarchical multiple regression analyses indicated that among those who were classified as exercise initiates (n = 33), self-efficacy and proxy efficacy accounted for 34 percent of the variance in exercise class attendance with the latter variable explaining a unique 12 percent. Consistent with theorizing, these preliminary findings indicate that for instructor-led, group physical activities such as aerobics classes, proxy efficacy perceptions are related to self-efficacy and may also be an important predictor of exercise behavior. PMID- 22049391 TI - Predicting Intended and Self-perceived Sugar Restriction among Tanzanian Students using the Theory of Planned Behavior. AB - This study examines the applicability and sufficiency of the Theory of Planned Behavior (TPB) in predicting intention and self-perceived behavior with respect to avoiding between-meal intake of sugared snacks and drinks. One thousand one hundred and twenty-three Tanzanian students (mean age 26.4 years) completed self administered questionnaires designed to measure the components of the TPB during May-July, 1999. Self-perceived sugar consumption was obtained in a subsample of respondents (n = 228) four weeks later. The TPB provided a significant prediction of intention (R(2)= 0.44), with attitude (= 0.25), subjective norms (= 0.28) and perceived behavioral control (= 0.35) significant, and subsequent behavior (R(2) = 0.15, with intention (= 0.25) and perceived behavioral control (= 0.18) significant. Frequency of past behavior explained a significant, albeit small, amount of additional variance in intention (1 percent) and behavior (4 percent). The results indicate that the TPB is applicable to the prediction of food choice related intention and behavior among young adult students living in a non occidental setting. PMID- 22049392 TI - A structural evaluation of the expanded multidimensional health locus of control scale with a diverse sample of caucasian/european, native, and black canadian women. AB - The Multidimensional Health Locus of Control (MHLC) scale is a widely used measure of the factors that people believe exert some control over their health. The purpose of the research reported here is to provide an independent evaluation of the structural properties of the recently expanded MHLC. Specifically we sought to address the issue of the interdependence of the external locus of control scales (Powerful Others, God, and Chance) and the legitimacy of the addition of a measure of God control as a separate subscale in the expanded MHLC. The study is based on an ethnically diverse sample of 371 community women, recruited through a random digit dialing procedure, who responded to all the items on the expanded MHLC. Although, the three external factors (God, Powerful Others, and Chance) are substantially correlated, structural analyses indicate that a four-factor model consisting of the three external scales and the Internal control scale provides the best fit to the observed covariances among the items. We view this result as supporting the addition of the God subscale as a separate dimension of external health locus of control. We also find support in these results for the continued scoring of four subscales on the MHLC rather than combining the three external subscales on one dimension as some have suggested. PMID- 22049394 TI - The psychology of couples and illness. PMID- 22049393 TI - Subliminal perception: biased attributions in matching persons with drawings of germs? AB - Subliminal perception was used to explore the magical contagion paradigm and ascertain whether drawings of germs perceived as harmful or threatening would be assumed to belong to members of stigmatized groups. In study 1, descriptions of persons (primes) were shown subliminally for 50 milliseconds and participants chose which germ they felt belonged to that person after the presentation. The germs perceived as least harmful and threatening were assigned to participants' best friends' first names, subjects' own first names, and young Hispanic persons. The groups of persons assigned the most harmful and threatening germs were older black and older Hispanic persons. In study 2, primes were shown for a longer period of time that allowed for conscious processing and males were assigned the more harmful germs at a statistically significant rate. PMID- 22049395 TI - Producing Patient-centered Health Care: Patient Perspectives about Health and Illness and the Physician/Patient Relationship. PMID- 22049396 TI - Psychology of medicine and surgery: a guide for psychologists, counsellors, nurses and doctors. PMID- 22049397 TI - The social construction of anorexia nervosa. PMID- 22049398 TI - Erratum volume 6 issue 2. PMID- 22049399 TI - Norepinephrine reduces omega-conotoxin-sensitive Ca2+ currents in renal afferent neurons in rats. AB - Sympathetic efferent and peptidergic afferent renal nerves likely influence hypertensive and inflammatory kidney disease. Our recent investigation with confocal microscopy revealed that in the kidney sympathetic nerve endings are colocalized with afferent nerve fibers (Ditting T, Tiegs G, Rodionova K, Reeh PW, Neuhuber W, Freisinger W, Veelken R. Am J Physiol Renal Physiol 297: F1427-F1434, 2009; Veelken R, Vogel EM, Hilgers K, Amman K, Hartner A, Sass G, Neuhuber W, Tiegs G. J Am Soc Nephrol 19: 1371-1378, 2008). However, it is not known whether renal afferent nerves are influenced by sympathetic nerve activity. We tested the hypothesis that norepinephrine (NE) influences voltage-gated Ca(2+) channel currents in cultured renal dorsal root ganglion (DRG) neurons, i.e., the first order neuron of the renal afferent pathway. DRG neurons (T11-L2) retrogradely labeled from the kidney and subsequently cultured, were investigated by whole cell patch clamp. Voltage-gated calcium channels (VGCC) were investigated by voltage ramps (-100 to +80 mV, 300 ms, every 20 s). NE and appropriate adrenergic receptor antagonists were administered by microperfusion. NE (20 MUM) reduced VGCC-mediated currents by 10.4 +/- 3.0% (P < 0.01). This reduction was abolished by the alpha-adrenoreceptor inhibitor phentolamine and the alpha(2)-adrenoceptor antagonist yohimbine. The beta-adrenoreceptor antagonist propranolol and the alpha(1)-adrenoceptor antagonist prazosin had no effect. The inhibitory effect of NE was abolished when N-type currents were blocked by omega-conotoxin GVIA, but was unaffected by other specific Ca(2+) channel inhibitors (omega-agatoxin IVA; nimodipine). Confocal microscopy revealed sympathetic innervation of DRGs and confirmed colocalization of afferent and efferent fibers within in the kidney. Hence NE released from intrarenal sympathetic nerve endings, or sympathetic fibers within the DRGs, or even circulating catecholamines, may influence the activity of peptidergic afferent nerve fibers through N-type Ca(2+) channels via an alpha(2)-adrenoceptor-dependent mechanism. However, the exact site and the functional role of this interaction remains to be elucidated. PMID- 22049400 TI - The p53 inhibitor pifithrin-alpha can stimulate fibrosis in a rat model of ischemic acute kidney injury. AB - Inhibition of the tumor suppressor p53 diminishes tubular cell apoptosis and protects renal function in animal models of acute kidney injury (AKI). Therefore, targeting p53 has become an attractive therapeutic strategy in the approach to AKI. Although the acute protective effects of p53 inhibition in AKI have been examined, there is still relatively little known regarding the impact of acute p53 inhibition on the chronic sequelae of AKI. Consequently, we utilized the p53 inhibitor pifithrin-alpha to examine the long-term effects of p53 inhibition in a rodent model of ischemic AKI. Male Sprague-Dawley rats were subjected to bilateral renal artery clamping for 30 min followed by reperfusion for up to 8 wk. Pifithrin-alpha or vehicle control was administered at the time of surgery and then daily for 2 days [brief acute administration (BA)] or 7 days [prolonged acute administration (PA)]. Despite the acute protective effect of pifithrin alpha in models of ischemic AKI, we found no protection in the microvascular rarefaction at 4 wk or development fibrosis at 8 wk with pifithrin-alpha administered on the BA schedule compared with vehicle control-treated animals. Furthermore, pifithrin-alpha administered on a PA schedule actually produced worse fibrosis compared with vehicle control animals after ischemic injury [21%/area (SD4.4) vs.16%/area (SD3.6)] as well as under sham conditions [2.6%/area (SD1.8) vs. 4.7%/area (SD1.3)]. The development of fibrosis with PA administration was independent of microvascular rarefaction. We identified enhanced extracellular matrix production, epithelial-to-mesenchymal transition, and amplified inflammatory responses as potential contributors to the augmented fibrosis observed with PA administration of pifithrin-alpha. PMID- 22049401 TI - Neuromodulation in a rat model of the bladder micturition reflex. AB - A rat model of bladder reflex contraction (BRC) was used to determine the optimal frequency and intensity of spinal nerve (SN) stimulation to produce neuromodulation of bladder activity and to assess the therapeutic mechanisms of this neuromodulation. In anesthetized female rats (urethane 1.2 g/kg ip), a wire electrode was used to produce bilateral stimulation of the L6 SN. A cannula was placed into the bladder via the urethra, and the urethra was ligated to ensure an isovolumetric bladder. Saline infusion induced BRC. Electrical stimulation of the SN produced a frequency- and intensity-dependent attenuation of the frequency of bladder contractions. Ten-herz stimulation produced maximal inhibition; lower and higher stimulation frequency produced less attenuation of BRC. Attenuation of bladder contraction frequency was directly proportional to the current intensity. At 10 Hz, stimulation using motor threshold pulses (T(mot)) produced a delayed inhibition of the frequency of bladder contractions to 34 +/- 11% of control. Maximal bladder inhibition appeared at 10 min poststimulation. High current intensity at 0.6 mA (~6 * T(mot)) abolished bladder contraction during stimulation, and the inhibition was sustained for 10 min poststimulation (prolonged inhibition). Furthermore, in rats pretreated with capsaicin (125 mg/kg sc), stimulation produced a stronger inhibition of BRC. The inhibitory effects on bladder contraction may be mediated by both afferent and efferent mechanisms. Lower intensities of stimulation may activate large, fast-conducting fibers and actions through the afferent limb of the micturition reflex arc in SN neuromodulation. Higher intensities may additionally act through the efferent limb. PMID- 22049402 TI - Doxorubicin-induced glomerulosclerosis with proteinuria in GFP-GABARAP transgenic mice. AB - Autophagy is a process of cellular degradation, and its dysfunction elicits many pathological symptoms. However, the contribution of autophagy to kidney glomerular function has not been fully clarified. We previously reported that LC3, a promising executor of autophagy, played an important role in recovery from podocyte damage in an experimental nephrosis model (Asanuma K, Tanida I, Shirato I, Ueno T, Takahara H, Nishitani T, Kominami E, Tomino Y. FASEB J 17: 1165-1167, 2003). gamma-Aminobutyric acid A receptor-associated protein (GABARAP), has recently been characterized as another homolog of LC3, although its precise role in autophagy remains unclear. We recently generated green fluorescent protein (GFP)-GABARAP transgenic mice, in which GFP-GABARAP is abundantly expressed in glomerular podocytes. We found that the transgenic mice showed no obvious phenotype, and podocytes isolated from these mice manifested autophagic activity almost equivalent to that of wild-type mice when measured in vitro. Surprisingly, a single injection of doxorubicin caused a greater increase in proteinuria and sclerotic glomeruli in transgenic mice compared with wild-type mice. Under these conditions, neither GFP-GABARAP nor endogenous GABARAP appeared to be recruited to autophagosomes, and both remained in the cytosol. Moreover, the cytosolic GFP GABARAP was significantly colocalized with p62 to form aggregates. These results indicate that the GFP-GABARAP/p62 complex is responsible for impairment of glomerular function and that it retards recovery from the effects of doxorubicin. PMID- 22049403 TI - Vocal fold phase asymmetries in patients with voice disorders: a study across visualization techniques. AB - PURPOSE: To examine differences in vocal fold vibratory phase asymmetry judged from stroboscopy, high-speed videoendoscopy (HSV), and the HSV-derived playbacks of mucosal wave kymography, digital kymography, and a static medial digital kymography image of persons with hypofunctional and hyperfunctional voice disorders. Differences between the methods of visual judgments and objective measures of left-right phase asymmetry were assessed. The findings were compared with those from a previous study with vocally normal speakers. METHOD: Forty-nine persons with voice disorders underwent stroboscopy and HSV. The HSV images were processed, resulting in 4 different spatial or kymographic displays. Two types of phase asymmetries, left-right and anterior-posterior, were visually rated. Objective measures of left-right phase asymmetry were obtained. RESULTS: From stroboscopy, the HSV playback, and the HSV-derived playbacks, left-right phase symmetry was judged to be symmetrical in 41%, 32%, and 19% of cases, respectively. This difference in playbacks was not seen for anterior-posterior asymmetry. Correlation between visual judgments and objective measures was mild for stroboscopy and moderate to high for all HSV-based playbacks. CONCLUSIONS: The use of kymography appears important for judgments of phase asymmetry. Stroboscopy appears to be sensitive, but possibly not specific, to phase asymmetries. Further development of objective measures is warranted for this feature. PMID- 22049404 TI - Development of the communication complexity scale. AB - PURPOSE: Accurate description of an individual's communication status is critical in both research and practice. Describing the communication status of individuals with severe intellectual and developmental disabilities is difficult because these individuals often communicate with presymbolic means that may not be readily recognized. Our goal was to design a communication scale and summary score for interpretation that could be applied across populations of children and adults with limited (often presymbolic) communication forms. METHOD: The Communication Complexity Scale (CCS) was developed by a team of researchers and tested with 178 participants with varying levels of presymbolic and early symbolic communication skills. Correlations between standardized and informant measures were completed, and expert opinions were obtained regarding the CCS. RESULTS: CCS scores were within expected ranges for the populations studied, and interrater reliability was high. Comparison across other measures indicated significant correlations with standardized tests of language. Scores on informant report measures tended to place children at higher levels of communication. Expert opinions generally favored the development of the CCS. CONCLUSIONS: The scale appears to be useful for describing a given individual's level of presymbolic or early symbolic communication. Further research is needed to determine whether it is sensitive to developmental growth in communication. PMID- 22049405 TI - Macrostructural narrative language of adolescents and young adults with Down syndrome or fragile X syndrome. AB - PURPOSE: To gain a better understanding of language abilities, the expressive macrostructural narrative language abilities of verbally expressive adolescents and young adults with Down syndrome (DS) and those with fragile X syndrome (FXS) were examined. METHOD: The authors evaluated 24 adolescents and young adults with DS, 12 male adolescents and young adults with FXS, and 21 younger children with typical development (TD). Narrative samples were assessed at the macrostructural level using the narrative scoring scheme (Heilmann, Miller, Nockerts, & Dunaway, 2010). Three group comparisons were made using (a) the full sample matched on nonverbal mental age, (b) a subset of the participants individually matched on nonverbal mental age, and (c) a subset of participants individually matched on mean length of utterance. RESULTS: Study analyses revealed that the DS and FXS groups significantly outperformed the TD group on a limited number of narrative scoring scheme measures. No significant differences emerged between the DS and FXS groups. CONCLUSIONS: The study's results suggest that some aspects of macrostructural narrative language may be relative strengths for adolescents and young adults with DS and those with FXS. These results can be used to create more nuanced and informed approaches to assessment and intervention for these populations. PMID- 22049406 TI - Modulation of GABA transport by adenosine A1R-A2AR heteromers, which are coupled to both Gs- and G(i/o)-proteins. AB - Astrocytes play a key role in modulating synaptic transmission by controlling the available extracellular GABA via the GAT-1 and GAT-3 GABA transporters (GATs). Using primary cultures of rat astrocytes, we show here that an additional level of regulation of GABA uptake occurs via modulation of the GATs by the adenosine A(1) (A(1)R) and A(2A) (A(2A)R) receptors. This regulation occurs through a complex of heterotetramers (two interacting homodimers) of A(1)R-A(2A)R that signal via two different G-proteins, G(s) and G(i/o), and either enhances (A(2A)R) or inhibits (A(1)R) GABA uptake. These results provide novel mechanistic insight into how G-protein-coupled receptor heteromers signal. Furthermore, we uncover a previously unknown mechanism in which adenosine, in a concentration dependent manner, acts via a heterocomplex of adenosine receptors in astrocytes to significantly contribute to neurotransmission at the tripartite (neuron-glia neuron) synapse. PMID- 22049407 TI - Event-related potentials elicited by errors during the stop-signal task. I. Macaque monkeys. AB - The error-related negativity (ERN) and positivity (Pe) are components of event related potential (ERP) waveforms recorded from humans and are thought to reflect performance monitoring. Error-related signals have also been found in single neuron responses and local-field potentials recorded in supplementary eye field and anterior cingulate cortex of macaque monkeys. However, the homology of these neural signals across species remains controversial. Here, we show that monkeys exhibit ERN and Pe components when they commit errors during a saccadic stop signal task. The voltage distributions and current densities of these components were similar to those found in humans performing the same task. Subsequent analyses show that neither stimulus- nor response-related artifacts accounted for the error-ERPs. This demonstration of macaque homologues of the ERN and Pe forms a keystone in the bridge linking human and nonhuman primate studies on the neural basis of performance monitoring. PMID- 22049408 TI - Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT/A). AB - Botulinum neurotoxin type A (BoNT/A) is a metalloprotease that blocks synaptic transmission via the cleavage of SNAP-25 (synaptosomal-associated protein of 25 kDa). BoNT/A is successfully used in clinical neurology for the treatment of several neuromuscular pathologies and pain syndromes. Despite its widespread use, relatively little is known on BoNT/A intracellular trafficking in neurons. Using the visual pathway as a model system, here we show that catalytically active BoNT/A is capable of undergoing anterograde axonal transport and transcytosis. Following BoNT/A injection into the rat eye, significant levels of BoNT/A-cleaved SNAP-25 appeared in the retinorecipient layers of the superior colliculus (SC). Anterograde propagation of BoNT/A effects required axonal transport, ruling out a systemic spread of the toxin. Cleaved SNAP-25 was present in presynaptic structures of the tectum, but retinal terminals were devoid of the immunoreactivity, indicative of transcytosis. Experiments based on sequential administration of BoNT/A and BoNT/E showed a persistent catalytic activity of BoNT/A in tectal cells following its injection into the retina. Our findings demonstrate that catalytically active BoNT/A is anterogradely transported from the eye to the SC and transcytosed to tectal synapses. These data are important for a more complete understanding of the mechanisms of action of BoNT/A. PMID- 22049409 TI - A new Prospero and microRNA-279 pathway restricts CO2 receptor neuron formation. AB - CO(2) sensation represents an interesting example of nervous system and behavioral evolutionary divergence. The underlying molecular mechanisms, however, are not understood. Loss of microRNA-279 in Drosophila melanogaster leads to the formation of a CO(2) sensory system partly similar to the one of mosquitoes. Here, we show that a novel allele of the pleiotropic transcription factor Prospero resembles the miR-279 phenotype. We use a combination of genetics and in vitro and in vivo analysis to demonstrate that Pros participates in the regulation of miR-279 expression, and that reexpression of miR-279 rescues the pros CO(2) neuron phenotype. We identify common target molecules of miR-279 and Pros in bioinformatics analysis, and show that overexpression of the transcription factors Nerfin-1 and Escargot (Esg) is sufficient to induce formation of CO(2) neurons on maxillary palps. Our results suggest that Prospero restricts CO(2) neuron formation indirectly via miR-279 and directly by repressing the shared target molecules, Nerfin-1 and Esg, during olfactory system development. Given the important role of Pros in differentiation of the nervous system, we anticipate that miR-mediated signal tuning represents a powerful method for olfactory sensory system diversification during evolution. PMID- 22049410 TI - The relationship between brain oscillations and BOLD signal during memory formation: a combined EEG-fMRI study. AB - Previous studies demonstrated that increases in the theta frequency band with concomitant decreases in the alpha/beta frequency band indicate successful memory formation. However, little is known about the brain regions and the cognitive processes that underlie these encoding-related oscillatory memory effects. We investigated this relationship using simultaneous EEG-fMRI recordings in humans during long-term memory encoding. In line with prior studies, we demonstrate that a decrease in beta power and an increase in theta power positively predict subsequent recall. In fMRI, stronger activity in the left inferior prefrontal cortex and the right parahippocampal gyrus correlated with successful memory formation. EEG source localization revealed that the subsequent memory effect in the beta band was localized in the left inferior prefrontal cortex, whereas the effect in the theta band was localized in medial temporal lobe regions. Trial-by trial correlations between EEG and BOLD activity showed that beta power correlated negatively with left inferior prefrontal cortex activity. This correlation was more pronounced for items that could later be successfully recalled compared to items later forgotten. Based on these findings, we suggest that beta oscillations in the left inferior prefrontal cortex indicate semantic encoding processes, whereas theta oscillations in the medial temporal lobe reflect the binding of an item to its spatiotemporal context. PMID- 22049411 TI - Geometric cues influence head direction cells only weakly in nondisoriented rats. AB - The influential hypothesis that environmental geometry is critical for spatial orientation has been extensively tested behaviorally, and yet findings have been conflicting. Head direction (HD) cells, the neural correlate of the sense of direction, offer a window into the processes underlying directional orientation and may help clarify the issue. In the present study, HD cells were recorded as rats foraged in enclosures of varying geometry, with or without simultaneous manipulation of landmarks and self-motion cues (path integration). All geometric enclosures had single-order rotational symmetry and thus completely polarized the environment. They also had unique features, such as corners, which could, in principle, act as landmarks. Despite these strongly polarizing geometric cues, HD cells in nondisoriented rats never rotated with these shapes. In contrast, when a cue card (white or gray) was added to one wall, HD cells readily rotated with the enclosure. When path integration was disrupted by disorienting the rat, HD cells rotated with the enclosure even without the landmark. Collectively, these findings indicate that geometry exerts little or no influence on heading computations in nondisoriented rats, but it can do so in disoriented rats. We suggest that geometric processing is only a weak influence, providing a backup system for heading calculations and recruited only under conditions of disorientation. PMID- 22049412 TI - The hippocampus supports both recollection and familiarity when memories are strong. AB - Recognition memory is thought to consist of two component processes--recollection and familiarity. It has been suggested that the hippocampus supports recollection, while adjacent cortex supports familiarity. However, the qualitative experiences of recollection and familiarity are typically confounded with a quantitative difference in memory strength (recollection > familiarity). Thus, the question remains whether the hippocampus might in fact support familiarity-based memories whenever they are as strong as recollection-based memories. We addressed this problem in a novel way by using the Remember/Know procedure, which allowed us to explicitly match the confidence and accuracy of Remember and Know decisions. As in earlier studies, recollected items had higher accuracy and confidence than familiar items, and hippocampal activity was higher for recollected items than for familiar items. Furthermore, hippocampal activity was similar for familiar items, misses, and correct rejections. When the accuracy and confidence of recollected and familiar items were matched, the findings were dramatically different. Hippocampal activity was now similar for recollected and familiar items. Importantly, hippocampal activity was also greater for familiar items than for misses or correct rejections (as well as for recollected items vs misses or correct rejections). Our findings suggest that the hippocampus supports both recollection and familiarity when memories are strong. PMID- 22049413 TI - The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer's disease. AB - Considerable evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the progression of Alzheimer's disease (AD). We examined the ability of the novel mitochondria-targeted antioxidant MitoQ (mitoquinone mesylate: [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cycloheexadienl-yl) decyl triphenylphosphonium methanesulfonate]) to prevent AD-like pathology in mouse cortical neurons in cell culture and in a triple transgenic mouse model of AD (3xTg-AD). MitoQ attenuated beta-amyloid (Abeta)-induced neurotoxicity in cortical neurons and also prevented increased production of reactive species and loss of mitochondrial membrane potential (Deltapsi(m)) in them. To determine whether the mitochondrial protection conferred by MitoQ was sufficient to prevent the emergence of AD-like neuropathology in vivo, we treated young female 3xTg-AD mice with MitoQ for 5 months and analyzed the effect on the progression of AD like pathologies. Our results show that MitoQ prevented cognitive decline in these mice as well as oxidative stress, Abeta accumulation, astrogliosis, synaptic loss, and caspase activation in their brains. The work presented herein suggests a central role for mitochondria in neurodegeneration and provides evidence supporting the use of mitochondria-targeted therapeutics in diseases involving oxidative stress and metabolic failure, namely AD. PMID- 22049415 TI - Selective inhibition of striatal fast-spiking interneurons causes dyskinesias. AB - Fast-spiking interneurons (FSIs) can exert powerful control over striatal output, and deficits in this cell population have been observed in human patients with Tourette syndrome and rodent models of dystonia. However, a direct experimental test of striatal FSI involvement in motor control has never been performed. We applied a novel pharmacological approach to examine the behavioral consequences of selective FSI suppression in mouse striatum. IEM-1460, an inhibitor of GluA2 lacking AMPARs, selectively blocked synaptic excitation of FSIs but not striatal projection neurons. Infusion of IEM-1460 into the sensorimotor striatum reduced the firing rate of FSIs but not other cell populations, and elicited robust dystonia-like impairments. These results provide direct evidence that hypofunction of striatal FSIs can produce movement abnormalities, and suggest that they may represent a novel therapeutic target for the treatment of hyperkinetic movement disorders. PMID- 22049414 TI - PKA/AKAP1 and PP2A/Bbeta2 regulate neuronal morphogenesis via Drp1 phosphorylation and mitochondrial bioenergetics. AB - Mitochondrial shape is determined by fission and fusion reactions, perturbation of which can contribute to neuronal injury and disease. Mitochondrial fission is catalyzed by dynamin-related protein 1 (Drp1), a large GTPase of the dynamin family that is highly expressed in neurons and regulated by various posttranslational modifications, including phosphorylation. We report here that reversible phosphorylation of Drp1 at a conserved Ser residue by an outer mitochondrial kinase (PKA/AKAP1) and phosphatase (PP2A/Bbeta2) impacts dendrite and synapse development in cultured rat hippocampal neurons. PKA/AKAP1-mediated phosphorylation of Drp1 at Ser656 increased mitochondrial length and dendrite occupancy, enhancing dendritic outgrowth but paradoxically decreasing synapse number and density. Opposing PKA/AKAP1, PP2A/Bbeta2-mediated dephosphorylation of Drp1 at Ser656 fragmented and depolarized mitochondria and depleted them from dendrites, stunting dendritic outgrowth but augmenting synapse formation. Raising and lowering intracellular calcium reproduced the effects of dephospho-Drp1 and phospho-Drp1on dendrite and synapse development, respectively, while boosting mitochondrial membrane potential with l-carnitine-fostered dendrite at the expense of synapse formation without altering mitochondrial size or distribution. Thus, outer mitochondrial PKA and PP2A regulate neuronal development by inhibiting and promoting mitochondrial division, respectively. We propose that the bioenergetic state of mitochondria, rather than their localization or shape per se, is the key effector of Drp1, altering calcium homeostasis to modulate neuronal morphology and connectivity. PMID- 22049416 TI - Synergy from silence in a combinatorial neural code. AB - The manner in which groups of neurons represent events in the external world is a central question in neuroscience. Estimation of the information encoded by small groups of neurons has shown that in many neural systems, cells carry mildly redundant information. These measures average over all the activity patterns of a neural population. Here, we analyze the population code of the salamander and guinea pig retinas by quantifying the information conveyed by specific multicell activity patterns. Synchronous spikes, even though they are relatively rare and highly informative, convey less information than the sum of either spike alone, making them redundant coding symbols. Instead, patterns of spiking in one cell and silence in others, which are relatively common and often overlooked as special coding symbols, were found to be mostly synergistic. Our results reflect that the mild average redundancy between ganglion cells that was previously reported is actually the result of redundant and synergistic multicell patterns, whose contributions partially cancel each other when taking the average over all patterns. We further show that similar coding properties emerge in a generic model of neural responses, suggesting that this form of combinatorial coding, in which specific compound patterns carry synergistic or redundant information, may exist in other neural circuits. PMID- 22049417 TI - Chronic 5-HT transporter blockade reduces DA signaling to elicit basal ganglia dysfunction. AB - Serotonin (5-HT)-selective reuptake inhibitors (SSRIs) are widely administered for the treatment of depression, anxiety, and other neuropsychiatric disorders, but response rates are low, and side effects often lead to discontinuation. Side effect profiles suggest that SSRIs inhibit dopaminergic activity, but mechanistic insight remains scarce. Here we show that in mice, chronic 5-HT transporter (5 HTT) blockade during adulthood but not during development impairs basal ganglia dependent behaviors in a dose-dependent and reversible fashion. Furthermore, chronic 5-HTT blockade reduces striatal dopamine (DA) content and metabolism. A causal relationship between reduced DA signaling and impaired basal ganglia dependent behavior is indicated by the reversal of behavioral deficits through L DOPA administration. Our data suggest that augmentation of DA signaling would reduce side effects and increase efficacies of SSRI-based therapy. PMID- 22049418 TI - Synaptic deficits are rescued in the p25/Cdk5 model of neurodegeneration by the reduction of beta-secretase (BACE1). AB - Alzheimer's disease (AD) is the most common cause of dementia, and is characterized by memory loss and cognitive decline, as well as amyloid beta (Abeta) accumulation, and progressive neurodegeneration. Cdk5 is a proline directed serine/threonine kinase whose activation by the p25 protein has been implicated in a number of neurodegenerative disorders. The CK-p25 inducible mouse model exhibits progressive neuronal death, elevated Abeta, reduced synaptic plasticity, and impaired learning following p25 overexpression in forebrain neurons. Levels of Abeta, as well as the APP processing enzyme, beta-secretase (BACE1), are also increased in CK-p25 mice. It is unknown what role increased Abeta plays in the cognitive and neurodegenerative phenotype of the CK-p25 mouse. In the current work, we restored Abeta levels in the CK-p25 mouse to those of wild-type mice via the partial genetic deletion of BACE1, allowing us to examine the Abeta-independent phenotype of this mouse model. We show that, in the CK-p25 mouse, normalization of Abeta levels led to a rescue of synaptic and cognitive deficits. Conversely, neuronal loss was not ameliorated. Our findings indicate that increases in p25/Cdk5 activity may mediate cognitive and synaptic impairment via an Abeta-dependent pathway in the CK-p25 mouse. These findings explore the impact of targeting Abeta production in a mouse model of neurodegeneration and cognitive impairment, and how this may translate into therapeutic approaches for sporadic AD. PMID- 22049419 TI - Emergence of persistent networks in long-term intracranial EEG recordings. AB - Over the past two decades, the increased ability to analyze network relationships among neural structures has provided novel insights into brain function. Most network approaches, however, focus on static representations of the brain's physical or statistical connectivity. Few studies have examined how brain functional networks evolve spontaneously over long epochs of continuous time. To address this, we examine functional connectivity networks deduced from continuous long-term electrocorticogram recordings. For a population of six human patients, we identify a persistent pattern of connections that form a frequency-band dependent network template, and a set of core connections that appear frequently and together. These structures are robust, emerging from brief time intervals (~100 s) regardless of cognitive state. These results suggest that a metastable, frequency-band-dependent scaffold of brain connectivity exists from which transient activity emerges and recedes. PMID- 22049420 TI - Diminished top-down control underlies a visual imagery deficit in normal aging. AB - Mental imagery is involved in a wide variety of cognitive abilities, including reasoning, spatial navigation, and memory. Cognitive aging is associated with impairments in these abilities, suggesting that diminished fidelity of mental images in older adults may be related to diverse cognitive deficits. However, an age-related deficit in mental imagery and its role in memory impairment is still a matter of debate. Previous human fMRI studies demonstrated that visual imagery activates representations in category-selective visual cortex via top-down control mechanisms. Here, we use fMRI to show that normal aging is associated with diminished selectivity of visual cortex activation during visual imagery, with a corresponding reduction in the selectivity of functional connections between prefrontal cortex and visual cortices. Moreover, a relationship between reduced imagery selectivity and visual memory in older adults was established. These results reveal that aging disrupts neural networks that subserve mental imagery and offers evidence of this as a factor in age-related memory decline. PMID- 22049421 TI - Rich-club organization of the human connectome. AB - The human brain is a complex network of interlinked regions. Recent studies have demonstrated the existence of a number of highly connected and highly central neocortical hub regions, regions that play a key role in global information integration between different parts of the network. The potential functional importance of these "brain hubs" is underscored by recent studies showing that disturbances of their structural and functional connectivity profile are linked to neuropathology. This study aims to map out both the subcortical and neocortical hubs of the brain and examine their mutual relationship, particularly their structural linkages. Here, we demonstrate that brain hubs form a so-called "rich club," characterized by a tendency for high-degree nodes to be more densely connected among themselves than nodes of a lower degree, providing important information on the higher-level topology of the brain network. Whole-brain structural networks of 21 subjects were reconstructed using diffusion tensor imaging data. Examining the connectivity profile of these networks revealed a group of 12 strongly interconnected bihemispheric hub regions, comprising the precuneus, superior frontal and superior parietal cortex, as well as the subcortical hippocampus, putamen, and thalamus. Importantly, these hub regions were found to be more densely interconnected than would be expected based solely on their degree, together forming a rich club. We discuss the potential functional implications of the rich-club organization of the human connectome, particularly in light of its role in information integration and in conferring robustness to its structural core. PMID- 22049422 TI - The laminar and temporal structure of stimulus information in the phase of field potentials of auditory cortex. AB - Recent studies have shown that the phase of low-frequency local field potentials (LFPs) in sensory cortices carries a significant amount of information about complex naturalistic stimuli, yet the laminar circuit mechanisms and the aspects of stimulus dynamics responsible for generating this phase information remain essentially unknown. Here we investigated these issues by means of an information theoretic analysis of LFPs and current source densities (CSDs) recorded with laminar multi-electrode arrays in the primary auditory area of anesthetized rats during complex acoustic stimulation (music and broadband 1/f stimuli). We found that most LFP phase information originated from discrete "CSD events" consisting of granular-superficial layer dipoles of short duration and large amplitude, which we hypothesize to be triggered by transient thalamocortical activation. These CSD events occurred at rates of 2-4 Hz during both stimulation with complex sounds and silence. During stimulation with complex sounds, these events reliably reset the LFP phases at specific times during the stimulation history. These facts suggest that the informativeness of LFP phase in rat auditory cortex is the result of transient, large-amplitude events, of the "evoked" or "driving" type, reflecting strong depolarization in thalamo-recipient layers of cortex. Finally, the CSD events were characterized by a small number of discrete types of infragranular activation. The extent to which infragranular regions were activated was stimulus dependent. These patterns of infragranular activations may reflect a categorical evaluation of stimulus episodes by the local circuit to determine whether to pass on stimulus information through the output layers. PMID- 22049423 TI - When attention wanders: how uncontrolled fluctuations in attention affect performance. AB - No matter how hard subjects concentrate on a task, their minds wander (Raichle et al., 2001; Buckner et al., 2008; Christoff et al., 2009; Killingsworth and Gilbert, 2010). Internal fluctuations cannot be measured behaviorally or from conventional neurophysiological measures, so their effects on performance have been difficult to study. Previously, we measured fluctuations in visual attention using the responses of populations of simultaneously recorded neurons in macaque visual cortex (Cohen and Maunsell, 2010). Here, we use this ability to investigate how attentional fluctuations affect performance. We found that attentional fluctuations have large and complex effects on performance, the sign of which depends on the difficulty of the perceptual judgment. As expected, attention greatly improves the detection of subtle changes in a stimulus. Surprisingly, we found that attending too strongly to a particular stimulus impairs the ability to notice when that stimulus changes dramatically. Our results suggest that all previously reported measures of behavioral performance should be viewed as amalgamations of different attentional states, whether or not those studies specifically addressed attention. PMID- 22049424 TI - Sustained firing of cartwheel cells in the dorsal cochlear nucleus evokes endocannabinoid release and retrograde suppression of parallel fiber synapses. AB - Neurons in many brain regions release endocannabinoids from their dendrites that act as retrograde signals to transiently suppress neurotransmitter release from presynaptic terminals. Little is known, however, about the physiological mechanisms of short-term endocannabinoid-mediated plasticity under physiological conditions. Here we investigate calcium-dependent endocannabinoid release from cartwheel cells (CWCs) of the mouse dorsal cochlear nucleus (DCN) in the auditory brainstem that provide feedforward inhibition onto DCN principal neurons. We report that sustained action potential firing by CWCs evokes endocannabinoid release in response to submicromolar elevation of dendritic calcium that transiently suppresses their parallel fiber (PF) inputs by >70%. Basal spontaneous CWC firing rates are insufficient to evoke tonic suppression of PF synapses. However, elevating CWC firing rates by stimulating PFs triggers the release of endocannabinoids and heterosynaptic suppression of PF inputs. Spike evoked suppression by endocannabinoids selectively suppresses excitatory synapses, but glycinergic/GABAergic inputs onto CWCs are not affected. Our findings demonstrate a mechanism of transient plasticity mediated by endocannabinoids that heterosynaptically suppresses subsets of excitatory presynaptic inputs to CWCs that regulates feedforward inhibition of DCN principal neurons and may influence the output of the DCN. PMID- 22049425 TI - Dopamine effects on human error processing depend on catechol-O-methyltransferase VAL158MET genotype. AB - Brain dopamine (DA) has been linked to error processing. Because high and low (vs medium) prefrontal cortex (PFC) DA levels may facilitate D2-receptor-related modulations of PFC neural activation patterns, we hypothesized that high and low DA predicts increased error-specific transitions of PFC activity. Male human participants (n = 169) were genotyped for the catechol-O-methyltransferase (COMT) Val158Met polymorphism, associated with low (Val) and medium (Met) PFC DA levels. In addition, DRD2TaqIa and 5-HTTLPR, associated with striatal D(2) receptor density and serotonin uptake, respectively, were assessed. Participants received placebo or a selective DA-D(2) receptor blocker (sulpiride, 200 mg) and performed a Flanker task. EEG was recorded and decomposed into independent brain components (ICs) using independent component analysis. After errors, participants displayed (1) a negative deflection in ICs source-localized to the proximity of the anterior midcingulate cortex [IC-error-related negativity (IC-ERN)], (2) increased midcingulate cortex IC power in the delta/theta frequency range, and (3) slowing in the subsequent trial [posterror slowing (PES)]. Importantly, all, IC-ERN, delta/theta power, and PES were modulated by COMT * Substance interactions such that the Val allele predicted elevated IC-ERN, delta/theta power, and PES after placebo; this association was reversed under sulpiride. Because low doses of sulpiride presumably increase PFC DA levels, the COMT * Substance interaction supports the hypothesis that low (Val, placebo) and high (Met, sulpiride) versus medium (Val, sulpiride; Met, placebo) DA levels elevate reactivity to errors. Consistent with an influence of serotonin on PFC DA, the COMT * Substance interaction was modulated by 5-HTTLPR. PMID- 22049426 TI - In vivo pathogenic role of mutant SOD1 localized in the mitochondrial intermembrane space. AB - Mutations in Cu,Zn superoxide dismutase (SOD1) are associated with familial amyotrophic lateral sclerosis (ALS). Mutant SOD1 causes a complex array of pathological events, through toxic gain of function mechanisms, leading to selective motor neuron degeneration. Mitochondrial dysfunction is among the well established toxic effects of mutant SOD1, but its mechanisms are just starting to be elucidated. A portion of mutant SOD1 is localized in mitochondria, where it accumulates mostly on the outer membrane and inside the intermembrane space (IMS). Evidence in cultured cells suggests that mutant SOD1 in the IMS causes mitochondrial dysfunction and compromises cell viability. Therefore, to test its pathogenic role in vivo we generated transgenic mice expressing G93A mutant or wild-type (WT) human SOD1 targeted selectively to the mitochondrial IMS (mito SOD1). We show that mito-SOD1 is correctly localized in the IMS, where it oligomerizes and acquires enzymatic activity. Mito-G93ASOD1 mice, but not mito WTSOD1 mice, develop a progressive disease characterized by body weight loss, muscle weakness, brain atrophy, and motor impairment, which is more severe in females. These symptoms are associated with reduced spinal motor neuron counts and impaired mitochondrial bioenergetics, characterized by decreased cytochrome oxidase activity and defective calcium handling. However, there is no evidence of muscle denervation, a cardinal pathological feature of ALS. Together, our findings indicate that mutant SOD1 in the mitochondrial IMS causes mitochondrial dysfunction and neurodegeneration, but per se it is not sufficient to cause a full-fledged ALS phenotype, which requires the participation of mutant SOD1 localized in other cellular compartments. PMID- 22049427 TI - ClC-2 channels regulate neuronal excitability, not intracellular chloride levels. AB - Synaptic inhibition by GABA(A) receptors requires a transmembrane chloride gradient. Hyperpolarization or shunting results from outward current produced by chloride flowing down this gradient, into the cell. Chloride influx necessarily depletes the chloride gradient. Therefore, mechanisms that replenish the gradient (by reducing intracellular chloride concentration, [Cl(-)](i)) are crucial for maintaining the efficacy of GABA(A) receptor-mediated inhibition. ClC-2 is an inward-rectifying chloride channel that is thought to help extrude chloride because inward rectification should, in principle, allow ClC-2 to act as a one way chloride exit valve. But chloride efflux via ClC-2 nevertheless requires an appropriate driving force. Using computer modeling, we reproduced voltage-clamp experiments showing chloride efflux via ClC-2, but testing the same model under physiological conditions revealed that ClC-2 normally leaks chloride into the cell. The discrepancy is explained by the driving force conditions that exist under artificial versus physiological conditions, and by the fact that ClC-2 rectification is neither complete nor instantaneous. Thus, contrary to previous assertions that ClC-2 helps maintain synaptic inhibition by lowering [Cl(-)](i), our simulations show that ClC-2 mediates chloride influx, thus producing outward current and directly reducing excitability. To test how ClC-2 functions in real neurons, we used dynamic clamp to insert virtual ClC-2 channels into rat CA1 pyramidal cells with and without native ClC-2 channels blocked. Experiments confirmed that ClC-2 reduces spiking independently of inhibitory synaptic transmission. Our results highlight the importance of considering driving force when inferring how a channel functions under physiological conditions. PMID- 22049428 TI - Natural movies evoke spike trains with low spike time variability in cat primary visual cortex. AB - Neuronal responses in primary visual cortex have been found to be highly variable. This has led to the widespread notion that neuronal responses have to be averaged over large numbers of neurons to obtain suitably invariant responses that can be used to reliably encode or represent external stimuli. However, it is possible that the high variability of neuronal responses may result from the use of simple, artificial stimuli and that the visual cortex may respond differently to dynamic, naturalistic images. To investigate this question, we recorded the responses of primary visual cortical neurons in the anesthetized cat under stimulation with time-varying natural movies. We found that cortical neurons on the whole exhibited a high degree of spike count variability, but a surprisingly low degree of spike time variability. The spike count variability was further reduced when all but the first spike in a burst were removed. We also found that responses exhibiting low spike time variability exhibited low spike count variability, suggesting that rate coding and temporal coding might be more compatible than previously thought. In addition, we found the spike time variability to be significantly lower when stimulated by natural movies as compared with stimulation using drifting gratings. Our results indicate that response variability in primary visual cortex is stimulus dependent and significantly lower than previous measurements have indicated. PMID- 22049429 TI - Dynamic analysis of amyloid beta-protein in behaving mice reveals opposing changes in ISF versus parenchymal Abeta during age-related plaque formation. AB - Growing evidence supports the hypothesis that soluble, diffusible forms of the amyloid beta-peptide (Abeta) are pathogenically important in Alzheimer's disease (AD) and thus have both diagnostic and therapeutic salience. To learn more about the dynamics of soluble Abeta economy in vivo, we used microdialysis to sample the brain interstitial fluid (ISF), which contains the most soluble Abeta species in brain at steady state, in >40 wake, behaving APP transgenic mice before and during the process of Abeta plaque formation (age 3-28 months). Diffusible forms of Abeta, especially Abeta(42), declined significantly in ISF as mice underwent progressive parenchymal deposition of Abeta. Moreover, radiolabeled Abeta administered at physiological concentrations into ISF revealed a striking difference in the fate of soluble Abeta in plaque-rich (vs plaque-free) mice: it clears more rapidly from the ISF and becomes more associated with the TBS extractable pool, suggesting that cerebral amyloid deposits can rapidly sequester soluble Abeta from the ISF. Likewise, acute gamma-secretase inhibition in plaque free mice showed a marked decline of Abeta(38), Abeta(40), and Abeta(42), whereas in plaque-rich mice, Abeta(42) declined significantly less. These results suggest that most of the Abeta(42) that populates the ISF in plaque-rich mice is derived not from new Abeta biosynthesis but rather from the large reservoir of less soluble Abeta(42) in brain parenchyma. Together, these and other findings herein illuminate the in vivo dynamics of soluble Abeta during the development of AD type neuropathology and after gamma-secretase inhibition and help explain the apparent paradox that CSF Abeta(42) levels fall as humans develop AD. PMID- 22049430 TI - Morphological characterization of the entire interneuron population reveals principles of neuromere organization in the ventral nerve cord of Drosophila. AB - Decisive contributions to our understanding of the mechanisms underlying the development of the nervous system have been made by studies performed at the level of single, identified cells in the fruit fly Drosophila. While all the motor neurons and glial cells in thoracic and abdominal segments of the Drosophila embryo have been individually identified, few of the interneurons, which comprise the vast majority of cells in the CNS, have been characterized at this level. We have applied a single cell labeling technique to carry out a detailed morphological characterization of the entire population of interneurons in abdominal segments A1-A7. Based on the definition of a set of spatial parameters specifying axonal projection patterns and cell body positions, we have identified 270 individual cell types as the complete hemisegmental set of interneurons and placed these in an interactive database. As well as facilitating analyses of developmental processes, this comprehensive set of data sheds light on the principles underlying the formation and organization of an entire segmental unit of the CNS. PMID- 22049433 TI - Visual selection and the human frontal eye fields: effects of frontal transcranial magnetic stimulation on partial report analyzed by Bundesen's theory of visual attention. AB - While the frontal eye fields (FEF) are traditionally associated with eye movements, recent work indicates possible roles in controlling selective visual processing. We applied 10 Hz bursts of transcranial magnetic stimulation (TMS) over left or right human FEF while subjects performed a partial-report task that allowed quantitative estimates of top-down control and other parameters affecting visual performance. Participants selectively reported digits in a relevant color (targets) but not those in an irrelevant color (nontargets) from a brief masked display. A target could appear alone or together with an accompanying item (nontarget or target) in the same or opposite hemifield. Targets were normally identified better when presented with a nontarget than with another target, indicating prioritization of task-relevant targets and thus top-down control. We found this usual pattern of results without TMS, and also with TMS over left FEF. However, during right FEF TMS, the detrimental impact of accompanying distractors increased. Formal analysis in terms of Bundesen's (1990) theory of visual attention confirmed that right FEF TMS diminished the top-down control parameter for both hemifields, indicating an FEF role in top-down selection even for targets defined by the nonspatial property of color. Direct comparison with our previous findings for parietal TMS (Hung et al., 2005) confirmed the distinct role of FEF in top-down control, plus right-hemisphere predominance for this in humans. PMID- 22049431 TI - Light-evoked lateral GABAergic inhibition at single bipolar cell synaptic terminals is driven by distinct retinal microcircuits. AB - Inhibitory amacrine cells (ACs) filter visual signals crossing the retina by modulating the excitatory, glutamatergic output of bipolar cells (BCs) on multiple temporal and spatial scales. Reciprocal feedback from ACs provides focal inhibition that is temporally locked to the activity of presynaptic BC activity, whereas lateral feedback originates from ACs excited by distant BCs. These distinct feedback mechanisms permit temporal and spatial computation at BC terminals. Here, we used a unique preparation to study light-evoked IPSCs recorded from axotomized terminals of ON-type mixed rod/cone BCs (Mb) in goldfish retinal slices. In this preparation, light-evoked IPSCs could only reach axotomized BC terminals via the lateral feedback pathway, allowing us to study lateral feedback in the absence of overlapping reciprocal feedback components. We found that light evokes ON and OFF lateral IPSCs (L-IPSCs) in Mb terminals having different temporal patterns and conveyed via distinct retinal pathways. The relative contribution of rods versus cones to ON and OFF L-IPSCs was light intensity dependent. ACs presynaptic to Mb BC terminals received inputs via AMPA/KA- and NMDA-type receptors in both the ON and OFF pathways, and used TTX sensitive sodium channels to boost signal transfer along their processes. ON and OFF L-IPSCs, like reciprocal feedback IPSCs, were mediated by both GABA(A) and GABA(C) receptors. However, our results suggest that lateral and reciprocal feedback do not cross-depress each other, and are therefore mediated by distinct populations of ACs. These findings demonstrate that retinal inhibitory circuits are highly specialized to modulate BC output at different light intensities. PMID- 22049432 TI - Matrix metalloproteinase-9 and stromal cell-derived factor-1 act synergistically to support migration of blood-borne monocytes into the injured spinal cord. AB - The infiltration of monocytes into the lesioned site is a key event in the inflammatory response after spinal cord injury (SCI). We hypothesized that the molecular events governing the infiltration of monocytes into the injured cord involve cooperativity between the upregulation of the chemoattractant stromal cell-derived factor-1 (SDF-1)/CXCL12 in the injured cord and matrix metalloproteinase-9 (MMP-9/gelatinase B), expressed by infiltrating monocytes. SDF-1 and its receptor CXCR4 mRNAs were upregulated in the injured cord, while macrophages immunoexpressed CXCR4. When mice, transplanted with bone marrow cells from green fluorescent protein (GFP) transgenic mice, were subjected to SCI, GFP+ monocytes infiltrated the cord and displayed gelatinolytic activity. In vitro studies confirmed that SDF-1alpha, acting through CXCR4, expressed on bone marrow derived macrophages, upregulated MMP-9 and stimulated MMP-9-dependent transmigration across endothelial cell monolayers by 2.6-fold. There was a reduction in F4/80+ macrophages in spinal cord-injured MMP-9 knock-out mice (by 36%) or wild-type mice, treated with the broad-spectrum MMP inhibitor GM6001 (by 30%). Mice were adoptively transferred with myeloid cells and treated with the MMP-9/-2 inhibitor SB-3CT, the CXCR4 antagonist AMD3100, or a combination of both drugs. While either drug resulted in a 28-30% reduction of infiltrated myeloid cells, the combined treatment resulted in a 45% reduction, suggesting that SDF-1 and MMP-9 function independently to promote the trafficking of myeloid cells into the injured cord. Collectively, these observations suggest a synergistic partnership between MMP-9 and SDF-1 in facilitating transmigration of monocytes into the injured spinal cord. PMID- 22049434 TI - Attentional bias to briefly presented emotional distractors follows a slow time course in visual cortex. AB - A central controversy in the field of attention is how the brain deals with emotional distractors and to what extent they capture attentional processing resources reflexively due to their inherent significance for guidance of adaptive behavior and survival. Especially, the time course of competitive interactions in early visual areas and whether masking of briefly presented emotional stimuli can inhibit biasing of processing resources in these areas is currently unknown. We recorded frequency-tagged potentials evoked by a flickering target detection task in the foreground of briefly presented emotional or neutral pictures that were followed by a mask in human subjects. We observed greater competition for processing resources in early visual cortical areas with shortly presented emotional relative to neutral pictures ~275 ms after picture offset. This was paralleled by a reduction of target detection rates in trials with emotional pictures ~400 ms after picture offset. Our finding that briefly presented emotional distractors are able to bias attention well after their offset provides evidence for a rather slow feedback or reentrant neural competition mechanism for emotional distractors that continues after the offset of the emotional stimulus. PMID- 22049435 TI - Gamma responses correlate with temporal expectation in monkey primary visual cortex. AB - Gamma oscillations have been linked to selective attention. Here, we investigate the effects of expecting a behaviorally relevant event (a change in the fixation point) on the oscillatory patterning of the local field potential and spiking responses in V1. Three protocols were used. In the first protocol, fixation point change occurred at a fixed time point, enabling predictions on task timing. In the second, fixation point change occurred in trial blocks either early or late in the trial, allowing us to compare responses during epochs of low and high expectation. Finally, we used a cue to indicate the upcoming fixation point change. All protocols led to an increase in gamma oscillations associated with alpha suppression when the monkeys expected an event in time. These effects were spatially widespread, since comparable results were observed for both central and peripheral visual representations in V1. Our findings indicate that expectations associated with perceptual decisions, motor responses, or upcoming reward may have a strong effect on the primary visual cortex, causing global, spatially nonselective modulation of gamma activity. PMID- 22049436 TI - GABAergic synaptic plasticity during a developmentally regulated sleep-like state in C. elegans. AB - Approximately one-fourth of the neurons in Caenorhabditis elegans adults are born during larval development, indicating tremendous plasticity in larval nervous system structure. Larval development shows cyclical expression of sleep-like quiescent behavior during lethargus periods, which occur at larval stage transitions. We studied plasticity at the neuromuscular junction during lethargus using the acetylcholinesterase inhibitor aldicarb. The rate of animal contraction when exposed to aldicarb is controlled by the balance between excitatory cholinergic and inhibitory GABAergic input on the muscle. During lethargus, there is an accelerated rate of contraction on aldicarb. Mutant analysis and optogenetic studies reveal that GABAergic synaptic transmission is reduced during lethargus. Worms in lethargus show partial resistance to GABA(A) receptor agonists, indicating that postsynaptic mechanisms contribute to lethargus dependent plasticity. Using genetic manipulations that separate the quiescent state from the developmental stage, we show that the synaptic plasticity is dependent on developmental time and not on the behavioral state of the animal. We propose that the synaptic plasticity regulated by a developmental clock in C. elegans is analogous to synaptic plasticity regulated by the circadian clock in other species. PMID- 22049437 TI - An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis. AB - Orexin (hypocretin) neurons, located exclusively in the PeF-LH, which includes the perifornical area (PeF), the lateral hypothalamus (LH), and lateral portions of the medial hypothalamus, have widespread projections and influence many physiological functions, including the autonomic regulation of body temperature and energy metabolism. Narcolepsy is characterized by the loss of orexin neurons and by disrupted sleep, but also by dysregulation of body temperature and by a strong tendency for obesity. Heat production (thermogenesis) in brown adipose tissue (BAT) contributes to the maintenance of body temperature and, through energy consumption, to body weight regulation. We identified a neural substrate for the influence of orexin neurons on BAT thermogenesis in rat. Nanoinjection of orexin-A (12 pmol) into the rostral raphe pallidus (rRPa), the site of BAT sympathetic premotor neurons, produced large, sustained increases in BAT sympathetic outflow and in BAT thermogenesis. Activation of neurons in the PeF-LH also enhanced BAT thermogenesis over a long time course. Combining viral retrograde tracing from BAT, or cholera toxin subunit b tracing from rRPa, with orexin immunohistochemistry revealed synaptic connections to BAT from orexin neurons in PeF-LH and from rRPa neurons with closely apposed, varicose orexin fibers, as well as a direct, orexinergic projection from PeF-LH to rRPa. These results indicate a potent modulation of BAT thermogenesis by orexin released from the terminals of orexin neurons in PeF-LH directly into the rRPa and provide a potential mechanism contributing to the disrupted regulation of body temperature and energy metabolism in the absence of orexin. PMID- 22049438 TI - The effects of prefrontal cortex inactivation on object responses of single neurons in the inferotemporal cortex during visual search. AB - Inferotemporal cortex (IT) is believed to be directly involved in object processing and necessary for accurate and efficient object recognition. The frontal eye field (FEF) is an area in the primate prefrontal cortex that is involved in visual spatial selection and is thought to guide spatial attention and eye movements. We show that object-selective responses of IT neurons and behavioral performance are affected by changes in frontal eye field activity. This was found in monkeys performing a search classification task by temporarily inactivating subregions of FEF while simultaneously recording the activity from single neurons in IT. The effect on object selectivity and performance was specific, occurring in a predictable spatially dependent manner and was strongest when the IT neuron's preferred target was presented in the presence of distractors. FEF inactivation did not affect IT responses on trials in which the nonpreferred target was presented in the search array. PMID- 22049439 TI - Sensory network dysfunction, behavioral impairments, and their reversibility in an Alzheimer's beta-amyloidosis mouse model. AB - The unique vulnerability of the olfactory system to Alzheimer's disease (AD) provides a quintessential translational tool for understanding mechanisms of synaptic dysfunction and pathological progression in the disease. Using the Tg2576 mouse model of beta-amyloidosis, we show that aberrant, hyperactive olfactory network activity begins early in life, before detectable behavioral impairments or comparable hippocampal dysfunction and at a time when amyloid-beta (Abeta) deposition is restricted to the olfactory bulb (OB). Hyperactive odor evoked activity in the piriform cortex (PCX) and increased OB-PCX functional connectivity emerged at a time coinciding with olfactory behavior impairments. This hyperactive activity persisted until later in life when the network converted to a hyporesponsive state. This conversion was Abeta-dependent, because liver-X receptor agonist treatment to promote Abeta degradation rescued the hyporesponsive state and olfactory behavior. These data lend evidence to a novel working model of olfactory dysfunction in AD and, complimentary to other recent works, suggest that disease-relevant network dysfunction is highly dynamic and region specific, yet with lasting effects on cognition and behavior. PMID- 22049440 TI - Untuned suppression makes a major contribution to the enhancement of orientation selectivity in macaque v1. AB - One of the functions of the cerebral cortex is to increase the selectivity for stimulus features. Finding more about the mechanisms of increased cortical selectivity is important for understanding how the cortex works. Up to now, studies in multiple cortical areas have reported that suppressive mechanisms are involved in feature selectivity. However, the magnitude of the contribution of suppression to tuning selectivity is not yet determined. We use orientation selectivity in macaque primary visual cortex, V1, as an archetypal example of cortical feature selectivity and develop a method to estimate the magnitude of the contribution of suppression to orientation selectivity. The results show that untuned suppression, one form of cortical suppression, decreases the orthogonal to-preferred response ratio (O/P ratio) of V1 cells from an average of 0.38 to 0.26. Untuned suppression has an especially large effect on orientation selectivity for highly selective cells (O/P < 0.2). Therefore, untuned suppression is crucial for the generation of highly orientation-selective cells in V1 cortex. PMID- 22049441 TI - Opposing roles of voltage-gated Ca2+ channels in neuronal control of regenerative patterning. AB - There is intense interest in developing methods to regulate proliferation and differentiation of stem cells into neuronal fates for the purposes of regenerative medicine. One way to do this is through in vivo pharmacological engineering using small molecules. However, a key challenge is identification of relevant signaling pathways and therein druggable targets to manipulate stem cell behavior efficiently in vivo. Here, we use the planarian flatworm as a simple chemical-genetic screening model for nervous system regeneration to show that the isoquinoline drug praziquantel (PZQ) acts as a small molecule neurogenic to produce two-headed animals with integrated CNSs following regeneration. Characterization of the entire family of planarian voltage-operated Ca(2+) channel alpha subunits (Ca(v)alpha), followed by in vivo RNAi of specific Ca(v) subunits, revealed that PZQ subverted regeneration by activation of a specific voltage-gated Ca(2+) channel isoform (Ca(v)1A). PZQ-evoked Ca(2+) entry via Ca(v)1A served to inhibit neuronally derived Hedgehog signals, as evidenced by data showing that RNAi of Ca(v)1A prevented PZQ-evoked bipolarity, Ca(2+) entry, and decreases in wnt1 and wnt11-5 levels. Surprisingly, the action of PZQ was opposed by Ca(2+) influx through a closely related neuronal Ca(v) isoform (Ca(v)1B), establishing a novel interplay between specific Ca(v)1 channel isoforms, Ca(2+) entry, and neuronal Hedgehog signaling. These data map PZQ efficacy to specific neuronal Ca(v) complexes in vivo and underscore that both activators (Ca(v)1A) and inhibitors (Ca(v)1B) of Ca(2+) influx can act as small molecule neurogenics in vivo on account of the unique coupling of Ca(2+) channels to neuronally derived polarity cues. PMID- 22049442 TI - The synaptic ribbon is a site of phosphatidic acid generation in ribbon synapses. AB - Ribbon synapses continuously transmit graded membrane potential changes into changes of synaptic vesicle exocytosis and rely on intense synaptic membrane trafficking. The synaptic ribbon is considered central to this process. In the present study we asked whether tonically active ribbon synapses are associated with the generation of certain lipids, specifically the highly active signaling phospholipid phosphatidic acid (PA). Using PA-sensor proteins, we demonstrate that PA is enriched at mouse retinal ribbon synapses in close vicinity to the synaptic ribbon in situ. As shown by heterologous expression, RIBEYE, a main component of synaptic ribbons, is responsible for PA binding at synaptic ribbons. Furthermore, RIBEYE is directly involved in the synthesis of PA. Using various independent substrate binding and enzyme assays, we demonstrate that the B domain of RIBEYE possesses lysophosphatidic acid (LPA) acyltransferase (LPAAT) activity, which leads to the generation of PA from LPA. Since an LPAAT-deficient RIBEYE mutant does not recruit PA-binding proteins to artificial synaptic ribbons, whereas wild-type RIBEYE supports PA binding, we conclude that the LPAAT activity of the RIBEYE(B) domain is a physiologically relevant source of PA generation at the synaptic ribbon. We propose that PA generated at synaptic ribbons likely facilitates synaptic vesicle trafficking. PMID- 22049443 TI - Presynaptic gating of postsynaptically expressed plasticity at mature thalamocortical synapses. AB - Thalamocortical (TC) projections provide the major pathway for ascending sensory information to the mammalian neocortex. Arrays of these projections form synaptic inputs on thalamorecipient neurons, thus contributing to the formation of receptive fields (RFs) in sensory cortices. Experience-dependent plasticity of RFs persists throughout an organism's life span but in adults requires activation of cholinergic inputs to the cortex. In contrast, synaptic plasticity at TC projections is limited to the early postnatal period. This disconnect led to the widespread belief that TC synapses are the principal site of RF plasticity only in neonatal sensory cortices, but that they lose this plasticity upon maturation. Here, we tested an alternative hypothesis that mature TC projections do not lose synaptic plasticity but rather acquire gating mechanisms that prevent the induction of synaptic plasticity. Using whole-cell recordings and direct measures of postsynaptic and presynaptic activity (two-photon glutamate uncaging and two photon imaging of the FM 1-43 assay, respectively) at individual synapses in acute mouse brain slices that contain the auditory thalamus and cortex, we determined that long-term depression (LTD) persists at mature TC synapses but is gated presynaptically. Cholinergic activation releases presynaptic gating through M(1) muscarinic receptors that downregulate adenosine inhibition of neurotransmitter release acting through A(1) adenosine receptors. Once presynaptic gating is released, mature TC synapses can express LTD postsynaptically through group I metabotropic glutamate receptors. These results indicate that synaptic plasticity at TC synapses is preserved throughout the life span and, therefore, may be a cellular substrate of RF plasticity in both neonate and mature animals. PMID- 22049444 TI - Medial temporal lobe function and recognition memory: a novel approach to separating the contribution of recollection and familiarity. AB - Human neuroimaging studies of recognition memory have often been interpreted to mean that the hippocampus supports recollection but not familiarity. This interpretation is complicated by the fact that recollection-based decisions are typically associated with stronger memories than familiarity-based decisions. Some studies of source memory controlled for this difference in memory strength and found that hippocampal activity during learning predicted subsequent item memory strength while recollection-based memory (performance on source memory questions) was held at chance. This result suggests that the hippocampus is important for familiarity. However, a difficulty with this approach is that when source memory is assessed by asking specific, task-relevant source memory questions, participants who fail to answer the prescribed questions might nevertheless have available other (task-irrelevant) source information. Accordingly, successful item memory could still be associated with recollection. The present study used a novel method to assess item memory and source memory. Instead of responding to specific source questions, participants rated their source memory strength based on any information about the learning episode that was available to them. When subsequent source memory strength was held constant at the lowest possible level, we identified regions bilaterally in hippocampus, as well as in perirhinal cortex, where activity during learning increased as subsequent item memory increased in strength. In addition, activity in cortical regions (including prefrontal cortex) was related to source memory success independently of item memory strength. These findings suggest that activity in the hippocampus is related to the encoding of familiarity-based item memory, independent of subsequent recollection-based success. PMID- 22049446 TI - Gambling: an emerging area of concern for health psychologists. PMID- 22049447 TI - Accounts of Quitting among Older Ex-smokers with Smoking-related Disease. AB - This article uses a discourse analytic method to explore how a sample of ex smokers with smoking-related illness position themselves, and are positioned by, the language they use in their accounts of quitting. The article suggests that discursive constructions (having 'no choice' and getting 'another chance') used by the respondents position them in a way that constrains behaviour by closing down the option of smoking and/or opening up the possibility of change. In each telling, the respondents' (non-smoking) identities are confirmed anew and this affirmation may assist in sustaining the change and provide protection against relapse. Moreover, the article suggests that the development and exchange of these stories may contribute to the growth of shared beliefs about the experience of quitting, opening up the option of quitting for current smokers. In so doing, accounts of quitting provided by ex-smokers undermine or resist dominant social understandings that even among those highly motivated to stop smoking, quitting is a difficult, if not impossible, endeavour. PMID- 22049445 TI - Age-related alterations in neurons of the mouse retina. AB - The behavioral consequences of age-related alterations in neural function are well documented, but less is known about their cellular bases. To characterize such changes, we analyzed 14 molecularly identified subsets of mouse retinal projection neurons (retinal ganglion cells or RGCs) and interneurons (amacrine, bipolar, and horizontal cells). The retina thinned but expanded with age, maintaining its volume. There was minimal decline in the number of RGCs, interneurons, or photoreceptors, but the diameter of RGC dendritic arbors decreased with age. Together, the increased retinal area and the decreased dendritic area may lead to gaps in RGC coverage of the visual field. Axonal arbors of RGCs in the superior colliculus also atrophied with age, suggesting that the relay of visual information to central targets may decline over time. On the other hand, the laminar restriction of RGC dendrites and the interneuronal processes that synapse on them were not detectably disturbed, and RGC subtypes exhibited distinct electrophysiological responses to complex visual stimuli. Other neuronal types aged in different ways: amacrine cell arbors did not remodel detectably, whereas horizontal cell processes sprouted into the photoreceptor layer. Bipolar cells showed arbor-specific alterations: their dendrites sprouted but their axons remained stable. In summary, retinal neurons exhibited numerous age-related quantitative alterations (decreased areas of dendritic and axonal arbors and decreased density of cells and synapses), whereas their qualitative features (molecular identity, laminar specificity, and feature detection) were largely preserved. Together, these data reveal selective age-related alterations in neural circuitry, some of which could underlie declines in visual acuity. PMID- 22049448 TI - Getting more people on the stairs: the impact of a new message format. AB - Previous research has found that poster prompts are associated with significant increases in stair use. The present study examined the use of messages on the stair risers, as an alternative to posters, to encourage stair climbing. Observers monitored shoppers' stair and escalator use over a 2-week baseline and 6-week intervention period. The prevalence of stair use increased from a baseline value of 8.1 percent to 18.3 percent when the motivating messages were in place. This increase is greater than that found in studies that used poster prompts in shopping centre venues. The apparent advantage of stair-riser banners is discussed in terms of their visibility and attractiveness, as well as their capacity to present multiple messages likely to appeal to a broader constituency. It is concluded that promoters of physical activity should use colourful, tailored stair-riser banners, rather than posters, to encourage stair climbing. PMID- 22049449 TI - Attributions and misconceptions in angina: an exploratory study. AB - Although there have been a number of studies regarding attributions and misconceptions in people following a heart attack, there have been no comparable studies in people with angina. Semi-structured interviews were held with 20 people suffering from angina to discover their beliefs about angina, particularly those that may be misconceived or associated with maladaptive coping. Nineteen of the 20 participants held such beliefs. Stress was the most frequent causal attribution and misconceived angina avoidance strategies were cited by the majority. The beliefs about angina held by this sample may have implications for their health-related quality of life, if their experience mirrors that found within heart attack populations. PMID- 22049450 TI - Illness Identity and the Self-regulatory Model in Recovery from Early Stage Gynaecological Cancer. AB - Women in recovery from early stage gynaecological cancer have extremely good survival and low recurrence rates. Despite this, women continue to feel vulnerable to cancer recurrence for years after treatment. Semi-structured interviews were utilized to explore the factors involved in recovery from gynaecological cancer. This article argues that the illness identity of gynaecological cancer perpetuates a vulnerability to cancer recurrence. The absence of self-diagnosis prior to medical diagnosis is important in the formation of gynaecological cancer illness identity. A lack of self-diagnosis may be due to the 'normalization' of initial symptomatology. It is suggested that illness identity is responsible for maintaining fears of symptom-free cancer recurrence. The self-regulatory model is employed to explore this process, looking in particular at the reinforcement of reassurance needs. PMID- 22049451 TI - Assessing family members' motivational readiness and decision making for consenting to cadaveric organ donation. AB - This study assessed the applicability of two important components of the transtheoretical model of behavior change (TTM) to family consent for cadaveric organ donation. Men and women (N = 169), who consented or refused to donate the organs of a family member, completed a telephone survey reflecting the stage of change and decisional balance constructs. Psychometric analyses resulted in a two factor decisional balance scale: a seven-item scale representing negative perceptions of consent (cons), and a seven-item scale representing positive perceptions of consent (pros). The pros and cons were significantly associated with stage of readiness for donation consent and with the family consent decision. Research utilizing this measure has the potential to enhance intervention programs to increase donation consent rates. PMID- 22049452 TI - Feeling Indecent: Breast Cancer Screening Resistance of Mexican-descent Women. AB - This grounded theory study investigated how Mexican-descent women's traditional cultural beliefs, values, and norms regarding the propriety of their behavior and that of their health care providers influence their decision to participate in breast cancer screening. Thirty-four women (aged 49-81 years old) were interviewed in five focus groups using theoretical sampling across levels of acculturation and socioeconomic status. We discovered that the women's basic social-psychological problem is that screening is an insensitive procedure that violates their cultural standards by requiring inappropriate behavior. The risk involved is 'feeling indecent' since both touching one's breast and breast exposure to health care providers is prohibited according to cultural norms for respectable female behavior. Thus, women resist participating in breast cancer screening to avoid feeling indecent. PMID- 22049453 TI - The psychosocial impact of spasticityrelated problems for people with multiple sclerosis: a focus group study. AB - This focus group, qualitative study (N = 18) reports the psychosocial impact, specifically, of spasticity symptoms on a sample of people with MS (multiple sclerosis). MS, a chronic disabling disease which attacks the central nervous system, currently affects about 100,000 people in the UK and estimates indicate that worldwide prevalence varies from around 10 to 250 per 100,000. The cause remains unknown and the rate of disease progression varies among individuals. The disease of MS itself has a severe impact on psychological well-being and quality of life. However, there is little evidence about the additional impact of the spasticity-related symptoms, which include involuntary muscle contractions, loss of dexterity, loss of balance, incontinence and pain. These are shown here to lead to further distress and embarrassment and to have a detrimental influence on emotional and social relationships. PMID- 22049454 TI - Parents of Children with Autism using an Email Group: A Grounded Theory Study. AB - Parents of children with autism have difficulties obtaining adequate information and support to guide them in the care of their children. However, the growth of communication technologies such as email has created greater opportunities for accessing such resources. This article presents a grounded theory analysis of the messages sent to an email group by parents of children with autism. The core category emerging from the analysis indicates that the group functioned in making sense of autism. The core category comprises four categories: searching for meaning; adjusting to changes; providing support and encouragement; and narrative sharing of experiences. Although email groups function as a social support mechanism, we suggest that this is not the only legitimate function: such groups may contribute towards the development of parental representations of autism. PMID- 22049455 TI - Cue-responding in a Simulated Bad News Situation: Exploring a Stress Hypothesis. AB - The stress-coping paradigm of Folkman and Lazarus (1984) was applied to investigate if the communicative reactions of the physician in a bad news transaction are related to the stressfulness of the situation. A standardized video bad news consultation was presented to 88 medical students. To examine their communicative reactions we selected 10 patient cues with different levels of expressed emotion to which the participants responded from the physician's point of view. A strongly positive relationship between expressed emotion and perceived difficulty of the cues and a gender effect occurred, confirming that handling emotions is stressful for physicians. The reluctance of physicians to address the emotionally laden issues of the consultation can be understood as a lack of a frame of reference. The problem-solving strategies, which they apply in the instrumental domain of the consultation, are ineffective when dealing with psychosocial suffering. PMID- 22049456 TI - Consumer/Provider communication research: a personal plea to address issues of ecological validity, relational development, message diversity and situational constraints. PMID- 22049458 TI - Introducing narrative psychology: self, trauma and the construction of meaning. PMID- 22049457 TI - Positive initiatives for people with learning difficulties: promoting healthy lifestyles. PMID- 22049459 TI - Premature menopause: a multidisciplinary approach whurr. PMID- 22049460 TI - Handbook of gender, culture, and health. PMID- 22049461 TI - Targeting angiogenesis using a C-type atrial natriuretic factor-conjugated nanoprobe and PET. AB - Sensitive, specific, and noninvasive detection of angiogenesis would be helpful in discovering new strategies for the treatment of cardiovascular diseases. Recently, we reported the (64)Cu-labeled C-type atrial natriuretic factor (CANF) fragment for detecting the upregulation of natriuretic peptide clearance receptor (NPR-C) with PET on atherosclerosis-like lesions in an animal model. However, it is unknown whether NPR-C is present and overexpressed during angiogenesis. The goal of this study was to develop a novel CANF-integrated nanoprobe to prove the presence of NPR-C and offer sensitive detection with PET during development of angiogenesis in mouse hind limb. METHODS: We prepared a multifunctional, core shell nanoparticle consisting of DOTA chelators attached to a poly(methyl methacrylate) core and CANF-targeting moieties attached to poly(ethylene glycol) chain ends in the shell of the nanoparticle. Labeling of this nanoparticle with (64)Cu yielded a high-specific-activity nanoprobe for PET imaging NPR-C receptor in a mouse model of hind limb ischemia-induced angiogenesis. Histology and immunohistochemistry were performed to assess angiogenesis development and NPR-C localization. RESULTS: (15)O-H(2)O imaging showed blood flow restoration in the previously ischemic hind limb, consistent with the development of angiogenesis. The targeted DOTA-CANF-comb nanoprobe showed optimized pharmacokinetics and biodistribution. PET imaging demonstrated significantly higher tracer accumulation for the targeted DOTA-CANF-comb nanoprobe than for either the CANF peptide tracer or the nontargeted control nanoprobe (P < 0.05, both). Immunohistochemistry confirmed NPR-C upregulation in the angiogenic lesion with colocalization in both endothelial and smooth muscle cells. PET and immunohistochemistry competitive receptor blocking verified the specificity of the targeted nanoprobe to NPR-C receptor. CONCLUSION: As evidence of its translational potential, this customized DOTA-CANF-comb nanoprobe demonstrated superiority over the CANF peptide alone for imaging NPR-C receptor in angiogenesis. PMID- 22049462 TI - Serial semiquantitative imaging of brain damage using micro-SPECT and micro-CT after endothelin-1-induced transient focal cerebral ischemia in rats. AB - In this study, we validated the use of (99m)Tc-hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) micro-SPECT combined with micro-CT for semiquantification of the infarct size after an experimental stroke in rats and compared our observations with those obtained from histology. This imaging strategy was applied to measure the longitudinal effect of mild hypothermia on the progression of brain damage after stroke in rats. METHODS: The endothelin-1 model was used to elicit a transient focal cerebral ischemia in rats. This resulted in a reproducible insult in which the core is represented by the striatum and the penumbra by the cortex. Micro-SPECT and micro-CT images were taken at 1, 3, and 7 d after infusion of endothelin-1 and compared with those taken before the insult. After the last acquisition, rats were sacrificed and the infarct volume was determined via Nissl staining. The results obtained with micro-SPECT and micro-CT were compared with histology at the same time points. Mild hypothermia (33 degrees C) was induced for 2 h, starting 20 min after the insult. RESULTS: Brain damage was estimated using micro-SPECT and micro-CT and was reproducible with minimal interobserver variability. Normothermic stroke rats had reduced (99m)Tc-HMPAO uptake at 1 and 3 d after the insult, whereas hypothermia improved damage after stroke. These findings corroborate with histology at the same time points. At 1 wk after the insult, no reduction of radioactive uptake was observed in any treatment group. CONCLUSION: Micro-SPECT and micro-CT allow quick and reproducible semiquantification of brain damage as an interesting alternative to histology to measure the extent of infarcted tissue in small animals after stroke. PMID- 22049464 TI - Antiserotonergic properties of terguride in blood vessels, platelets, and valvular interstitial cells. AB - Serotonin (5-hydroxytryptamine; 5-HT) is involved in heart valve tissue fibrosis, pulmonary arterial fibrosis, and pulmonary hypertension. We aimed at characterizing the antiserotonergic properties of the ergot alkaloid derivative terguride [1,1-diethyl-3-(6-methyl-8alpha-ergolinyl)urea] by using functional receptor assays and valvular interstitial cell culture. Terguride showed no vasoconstrictor effect in porcine coronary arteries (5-HT(2A) receptor bioassay) and no relaxant effect in porcine pulmonary arteries (5-HT(2B) receptor bioassay). Terguride behaved as a potent antagonist at 5-HT(2A) receptors (noncompetitive antagonist parameter pD'2 9.43) and 5-HT(2B) receptors (apparent pA2 8.87). Metabolites of terguride (N"-monodeethylterguride and 6-norterguride) lacked agonism at both sites. N"-monodeethylterguride and 6-norterguride were surmountable antagonists at 5-HT(2A) receptors (pA2 7.82 and 7.85, respectively) and 5-HT(2B) receptors (pA2 7.30 and 7.11, respectively). Kinetic studies on the effects of terguride in pulmonary arteries showed that the rate to reach drug receptor equilibrium for terguride was fast. Washout experiments showed that terguride easily disappeared from the receptor biophase. Pretreatment with terguride inhibited 5-HT-induced amplification of ADP-stimulated human platelet aggregation (IC50 16 nM). In porcine valvular interstitial cells, 5-HT-induced activation of extracellular signal-regulated kinase (ERK) 1/2, an initiator of cellular proliferation and activity, was blocked by terguride as shown by Western blotting. In these cells, the stimulatory effect of 5-HT on [3H]proline incorporation (index of extracellular matrix collagen) was blocked by terguride. Because of the inhibition of both 5-HT(2A) and 5-HT(2B) receptors, platelet aggregation, and cellular proliferation and activity (ERK1/2 phosphorylation and collagen production) terguride may have therapeutic potential in the treatment of fibrotic disorders. PMID- 22049465 TI - The Relationship between Body Image and Depressed Mood in Adolescence: A 5-year Longitudinal Panel Study. AB - Much research interest has been devoted to reveal the psychosocial processes associated with the development of depressive symptoms during adolescence. One of the important factors that has been studied is body image. In a 5-year longitudinal investigation, we revealed and discussed the relationship between body image and depressed mood in a cohort of adolescents at ages 13, 15 and 18. Girls reported on average higher depressed mood levels and more negative body image than boys at all ages. However, the correlations between the variables were nearly as strong for boys as for girls. Structural equation modelling revealed that body image predicted change in depressed mood both for boys and girls, but at different ages. In contrast, we did not find any support for the existence of causal effects of depressed mood upon body image. PMID- 22049466 TI - Adopting the stage model for smoking acquisition in Japanese adolescents. AB - The purpose of the present study was to apply the stages of change model to smoking acquisition in Japanese adolescents. The participants were 556 senior and 1002 junior high school students who responded anonymously to the questionnaire. The findings of this study confirm that the stage model is indeed applicable to smoking acquisition in Japanese adolescents. It was clearly seen that the process involves four stages: pre-contemplation, contemplation, preparation, and action. Furthermore, the results showed that measures of self-efficacy decreased, while temptation increased from precontemplation to action stages. The pros of smoking behavior increased toward action stage, while the cons decreased. PMID- 22049467 TI - Depressive Symptoms and Smoking among US Black Adults: Absence of a Relationship. AB - Depressive symptoms play a major role in cigarette smoking among US White adults, but it is not known if this holds for US Blacks. Hence, the relationship between depressive symptoms and smoking was examined among 520 US Black adults sampled from 10 randomlyselected community census tracts. Results revealed no relationship between depression and smoking, but education levels did contribute; Black high school drop-outs were four times more likely than Black college graduates to be smokers. PMID- 22049468 TI - Women's Experience at the Time of Menopause: Accounting for Biological, Cultural and Psychological Embodiment. AB - In understanding health and illness, it has long been apparent that psychological and social aspects are as important as the biological explanations of the biomedical model. Recent studies of women's experience of menopause have demonstrated the psychological and social constructions of women's bodies, but have neglected to include individual embodiment and the notion of a social world that is inescapably embodied. This paper presents arguments for the consideration of an integrated approach to embodiment and, drawing upon recent theorizing, a conceptual framework that is able to take into account the integration of psyche, biology, and culture. The accounts of 80 New Zealand women, aged between 45 and 60, are analysed, using categories labelled, 'visceral', 'experiential', 'normative' and 'pragmatic', to provide a description of women's embodied and culturally embedded experience of menopause. The incorporation of these analytic categories, and the usefulness of the application of the model in contemporary applied work, is discussed. PMID- 22049469 TI - Re-appraising HIV Testing among Scottish Gay Men: The Impact of New HIV Treatments. AB - This paper explores Scottish gay men's understandings of HIV testing within the context of changes stemming from the availability of new treatments for HIV. Transcripts of one-toone interviews with 18 gay men were analysed together with those from four focus groups (n= 19) concerning HIV testing, HIV status and HIV risk management. Interpretative Phenomenological Analysis was employed to identify recurrent themes. We focus upon a rise of HIV-optimism, risk-complacency and HIV fatigue and chart the apparent transformation of HIV diagnosis from 'death sentence' to 'life sentence'. In turn, we explore how these changes have impacted upon HIV testing. As HIV management becomes increasingly medicalized, we highlight the ongoing need to attend to psychological and social issues. PMID- 22049470 TI - The Impact of Iatrogenically Acquired Hepatitis C Infection on the Well-being and Relationships of a Group of Irish Women. AB - The views of 32 women with iatrogenic Hepatitis C on its impact on their sense of wellbeing were elicited through focus groups. The views obtained were analysed using 'interpretative phenomenological analysis'. Accounts of profound fatigue, reactive depression, and deterioration in cognitive functioning predominated. Work outside and inside the home was severely curtailed or stopped. Marital relationships were affected, sometimes adversely, as were relationships with children and other family members. Participants experienced a general lack of understanding of their level of disability, yet also felt the need to shield others from worry. Overall results suggested that participants' compromised health was having a major impact on their sense of identity. PMID- 22049471 TI - Resources for Health: A Social-Ecological Intervention for Supporting Self management of Chronic Conditions. AB - There is a pressing need for practical interventions to support self-management of chronic illness that can be integrated with primary care, and that take into account the patient's social environment. This pilot study was conducted with low income clients of a community health center and focused on enhancing use of social-environmental resources supportive of self-management. Twenty-eight patients having at least one chronic illness, randomized to immediate versus delayed treatment conditions, met once with a health educator to develop a self management plan, and received one follow-up phone call and two newsletters. Significant improvements in use of community resources, minutes of physical activity, and medication adherence were obtained compared to control. Integrating brief self-management counseling with social environmental support appeared effective, although much more can be done to better link counseling to primary care practice. PMID- 22049472 TI - A Comparative Analysis of the SF-12 and the SF-36 among Ischaemic Heart Disease Patients. AB - This paper investigated whether the SF-12 could replace the SF-36 in the measurement of health status among ischaemic heart disease patients. The SF-36 and SF-12 were administered to 105 cardiac patients. The SF-36 summary scores were strongly correlated and similar to the SF-12 summary scores. Also, the SF-12 scores were as powerful as the SF-36 summary scores in discriminating between subgroups of patients categorized according to their self-reported health status or angina classification. It is suggested that when there is a need to collect routine information about cardiac patients' general physical and mental health, the SF-12 is preferable to the SF-36 because of its brevity and acceptability to patients. PMID- 22049473 TI - Components of the anger-hostility complex and symptom reporting in patients with coronary artery disease: a multi-measure study. AB - Multiple anger and hostility variables were investigated for associations with coronary artery disease (CAD) symptoms and to examine if those relationships were different for disease severity.Atwo year follow-up study of97 men with stenosed coronary arteries was undertaken. Questionnaires measured: nine forms of anger and hostility; Type A behaviour; anxiety; depression; social support; and ninesymptom measures. CAD severity was derived from clinicians' ratings of coronary angiograms. Results are four fold: anger-hostility variables are relatively unimportant predictors of symptoms compared with anxiety and depression; psychosocial measures (except for expressed anger) are uncorrelated with CAD severity, though correlate numerously with CAD symptoms; symptoms are not distinguishable empirically in terms of frequency, intensity and duration with regard to type ('angina pain', 'tiredness' and 'breathlessness and restricted mobility'); finally, CADsymptoms are unrelated to CAD severity. In conclusion, components of the angerhostility complex are of limited use for predicting CAD symptoms. However, anger expression is of utility for differentiating between CAD symptoms and disease severity. PMID- 22049475 TI - Social determinants of health. PMID- 22049474 TI - Coping and distress as predictors of glycemic control in diabetes. AB - This study attempts to identify the relative contribution of coping styles (task , emotion-oriented and avoidance) and anxiety and diabetes-related distress to glycemic control in IDDM (Insulin Dependent Diabetes Mellitus) patients. Recent research suggests that coping and distress may as well be determinants as consequences of certain characteristics of the illness and subject. This points to the need to control some of these variables in diabetic research. Ninety seven IDDM patients from an outpatient unit were included. Measures were self-report questionnaires (CISS, STAI-Y, PAID) and biological data (HbA1C i.e. metabolic control). When potential confounds were controlled for (current age, age at onset, gender, presence of complication), three main predictors of metabolic control could be isolated through hierarchical regression analysis: (1) presence of complications; (2) task-oriented coping style; and (3) diabetes-related distress. Three steps were included in predictors: illness and subject variables (step 1); coping styles (step 2); and negative emotions (step 3). Each step contributed to a significant increase in variance. Emotion-oriented coping style appeared as redundant with distress measures. Results suggest that the relations between psychological predictors and metabolic control would be closer in women. These results partly replicate other findings, and advocate for a better consideration of emotional factors in the prediction of blood glucose control in this disease. PMID- 22049476 TI - Male bodies: health, culture and identity. PMID- 22049477 TI - Women, health and the mind. PMID- 22049478 TI - Stress, coping and cardiovascular disease. PMID- 22049480 TI - Annual index. PMID- 22049481 TI - Questioning the specificity of ASRS-v1.1 to accurately detect ADHD in substance abusing populations. AB - OBJECTIVE: To assess the specificity of the Adult ADHD Self-Report Scale (ASRS v1.1) in detecting ADHD among individuals with substance use disorders (SUDs). METHOD: A chart review of 183 SUD patients was conducted. Patients were screened for ADHD with the ASRS-v1.1 and were later assessed by a psychiatrist specialized in ADHD. RESULTS: Among SUD patients scoring positive results on the ASRS-v1.1 for the presence of ADHD, the ADHD diagnosis could only be confirmed in 26% of the sample by an expert psychiatrist. CONCLUSION: The ASRS-v1.1 reports low specificity in detecting ADHD among SUD populations. PMID- 22049482 TI - The influence of community and the built environment on physical activity. AB - OBJECTIVE: To examine associations between the built environment and leisure-time physical activity (LTPA) among African Americans and Whites. METHOD: Independent and control variables were produced from the literature and theory to represent key components of built environment, sense of community, sociodemographic, and health status characteristics. Logistic regression analysis and descriptive statistics were used to measures correlative relationships with physical activity. RESULTS: Built environment elements, especially homeownership, were associated with LTPA, particularly among older African American rural residents. DISCUSSION: Recommendations include transferring the concept of community ownership to residents living in areas where rates of physical activity are low. PMID- 22049483 TI - Perceiving a negative event as central to one's identity partially mediates age differences in posttraumatic stress disorder symptoms. AB - OBJECTIVE: Older adults report fewer posttraumatic stress disorder (PTSD) symptoms than younger adults, but the reasons for this age difference are unclear. In the current study, the authors explored the extent to which they may be due to age differences in event centrality (the extent to which a person construes a stressful event as central to their identity). METHOD: A sample of older and younger adults nominated their most stressful event and completed measures of PTSD symptoms and event centrality. RESULTS: The results revealed that older adults were less likely to construe a stressful event as central to identity, even after controlling for type of event, how long ago the event occurred, and gender. In addition, the results of a mediation analysis indicated that age-related differences in event centrality partially mediated age-related differences in PTSD symptoms. DISCUSSION: The results are consistent with the Socioemotional Selectivity Theory view that older adults tend to use cognitive strategies designed to protect emotional health. PMID- 22049487 TI - Primary pulmonary arterial hypertension diagnosed via its ophthalmic features in an adult: diagnosis and therapeutic challenges. PMID- 22049489 TI - Cytomegalovirus associated corneal endotheliitis after penetrating keratoplasty in a patient with Fuchs corneal endothelial dystrophy. PMID- 22049491 TI - Diffuse ocular metastasis of ductal breast carcinoma following vitreoretinal surgery. Diffuse choroidal metastasis of ductal breast carcinoma after repeat vitreoretinal surgery. PMID- 22049497 TI - Three patients with desmoplastic tricholemmoma with an incidental histological surprise impacting on management. PMID- 22049499 TI - Diagnosis of maternally inherited diabetes and deafness (mitochondrial A3243G mutation) based on funduscopic appearance in an asymptomatic patient. PMID- 22049509 TI - Authors' response. PMID- 22049511 TI - Peripheral corneal ring due to hypercarotenaemia in a case of nutritional supplement abuse. PMID- 22049513 TI - Cyclic AMP response element-binding protein prevents endothelial permeability increase through transcriptional controlling p190RhoGAP expression. AB - Increased endothelial permeability contributes to the morbidity and mortality associated with chronic inflammatory diseases, including acute lung injury. Cyclic AMP response element-binding protein (CREB) transcriptional factor induces genes that regulate inflammation and vascular remodeling. However, the role of CREB in regulating endothelial barrier function is unknown. Here, we demonstrate that CREB maintains basal endothelial barrier function and suppresses endothelial permeability increase by diverse agonists such as thrombin, lipopolysaccharide, histamine, and VEGF. We show that CREB transcriptionally controls the expression of p190RhoGAP-A, a GTPase-activating protein that inhibits small GTPase RhoA. Impairing CREB function using small interfering RNA or dominant-negative (dn) CREB mutant (dn-CREB) markedly suppressed p190RhoGAP-A expression, increased RhoA activity, induced actin stress fiber formation, and produced an amplified and protracted increase in endothelial permeability in response to thrombin. Rescuing p190RhoGAP-A expression restored the permeability defect in dn-CREB-transducing endothelial cells. These findings were recapitulated in vivo because dn-CREB expression in mice vasculature increased basal lung microvessel permeability and exaggerated permeability increase induced by thrombin and lipopolysaccharide. Inhibiting RhoA signaling restored endothelial barrier dysfunction in the dn-CREB expressing lung microvasculature. These results uncover a pivotal role of CREB in regulating endothelial barrier function by restricting RhoA signaling through controlling p190RhoGAP-A expression. PMID- 22049514 TI - Antigen stored in dendritic cells after macropinocytosis is released unprocessed from late endosomes to target B cells. AB - B lymphocytes can be triggered in lymph nodes by nonopsonized antigens (Ag), potentially in their native form. However, the mechanisms that promote encounter of B lymphocytes with unprocessed antigens in lymph nodes are still elusive. We show here that antigens are detected in B cells in the draining lymph nodes of mice injected with live, but not fixed, dendritic cells (DCs) loaded with antigens. This highlights active processes in DCs to promote Ag transfer to B lymphocytes. In addition, antigen-loaded DCs found in the draining lymph node were CD103+. Using 3 different model Ag, we then show that immature DCs efficiently take up Ag by macropinocytosis and store the internalized material in late endocytic compartments. We find that DCs have a unique ability to release antigens from these compartments in the extracellular medium, which is controlled by Rab27. B cells take up the regurgitated Ag and the chemokine CXCL13, essential to attract B cells in lymph nodes, enhances this transfer. Our results reveal a unique property of DCs to regurgitate unprocessed Ag that could play an important role in B-cell activation. PMID- 22049515 TI - Increased serum soluble IL-15Ralpha levels in T-cell large granular lymphocyte leukemia. AB - Large granular lymphocyte (LGL) leukemia is a clonal lymphoproliferative disease of mature T and natural killer cells. The etiology of LGL leukemia is unknown. IL 15 is an inflammatory cytokine that stimulates T and natural killer cells and is critical for their survival and proliferation. IL-15 signals through a heterotrimeric receptor that is composed of a private receptor, IL-15Ralpha and IL-2/IL-15Rbeta and gamma(c) shared with IL-2. Using a newly developed assay, we demonstrated increased levels of soluble IL-15Ralpha in the serum of patients with T-LGL leukemia. Furthermore, IL-15Ralpha mRNA levels were also up-regulated in the PBMCs of these patients. FACS analysis indicated that IL-15Ralpha was expressed both on monocytes as well as on some CD8+ leukemic cells of the patients. Interestingly, the mRNA levels of IFN-gamma, a known inducer of IL 15Ralpha, were also up-regulated in patients' PBMCs. Moreover, PBMCs of some T LGL patients proliferated at higher levels in response to exogenously added IL-15 compared with those of normal donors. In summary, our study demonstrated increased expression of IL-15Ralpha in T-LGL leukemia. It is conceivable that higher IL-15Ralpha expression may lower IL-15 response threshold in vivo and, therefore, may contribute to the pathogenesis of the disease. PMID- 22049516 TI - Sphingosine-1-phosphate facilitates trafficking of hematopoietic stem cells and their mobilization by CXCR4 antagonists in mice. AB - CXCL12 and VCAM1 retain hematopoietic stem cells (HSCs) in the BM, but the factors mediating HSC egress from the BM to the blood are not known. The sphingosine-1-phosphate receptor 1 (S1P(1)) is expressed on HSCs, and S1P facilitates the egress of committed hematopoietic progenitors from the BM into the blood. In the present study, we show that both the S1P gradient between the BM and the blood and the expression of S1P(1) are essential for optimal HSC mobilization by CXCR4 antagonists, including AMD3100, and for the trafficking of HSCs during steady-state hematopoiesis. We also demonstrate that the S1P(1) agonist SEW2871 increases AMD3100-induced HSC and progenitor cell mobilization. These results suggest that the combination of a CXCR4 antagonist and a S1P(1) agonist may prove to be sufficient for mobilizing HSCs in normal donors for transplantation purposes, potentially providing a single mobilization procedure and eliminating the need to expose normal donors to G-CSF with its associated side effects. PMID- 22049518 TI - Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols. AB - We investigated whether body mass index (BMI) correlates with distinct outcomes in newly diagnosed acute promyelocytic leukemia (APL). The study population included 144 patients with newly diagnosed and genetically confirmed APL consecutively treated at a single institution. All patients received All-trans retinoic acid and idarubicin according to the GIMEMA protocols AIDA-0493 and AIDA 2000. Outcome estimates according to the BMI were carried out together with multivariable analysis for the risk of relapse and differentiation syndrome. Fifty-four (37.5%) were under/normal weight (BMI < 25), whereas 90 (62.5%) patients were overweight/obese (BMI >= 25). An increased BMI was associated with older age (P < .0001) and male sex (P = .02). BMI was the most powerful predictor of differentiation syndrome in multivariable analysis (odds ratio = 7.24; 95% CI, 1.50-34; P = .014). After a median follow-up of 6 years, the estimated cumulative incidence of relapse at 5 years was 31.6% (95% CI, 22.7%-43.8%) in overweight/obese and 11.2% (95% CI, 5.3%-23.8%) in underweight/normal weight patients (P = .029). Multivariable analysis showed that BMI was an independent predictor of relapse (hazard ratio = 2.45, 95% CI, 1.00-5.99, in overweight/obese vs under/normal weight patients, P = .049). An increased BMI at diagnosis is associated with a higher risk of developing differentiation syndrome and disease relapse in APL patients treated with AIDA protocols. PMID- 22049517 TI - Enucleation of human erythroblasts involves non-muscle myosin IIB. AB - Mammalian erythroblasts undergo enucleation, a process thought to be similar to cytokinesis. Although an assemblage of actin, non-muscle myosin II, and several other proteins is crucial for proper cytokinesis, the role of non-muscle myosin II in enucleation remains unclear. In this study, we investigated the effect of various cell-division inhibitors on cytokinesis and enucleation. For this purpose, we used human colony-forming unit-erythroid (CFU-E) and mature erythroblasts generated from purified CD34(+) cells as target cells for cytokinesis and enucleation assay, respectively. Here we show that the inhibition of myosin by blebbistatin, an inhibitor of non-muscle myosin II ATPase, blocks both cell division and enucleation, which suggests that non-muscle myosin II plays an essential role not only in cytokinesis but also in enucleation. When the function of non-muscle myosin heavy chain (NMHC) IIA or IIB was inhibited by an exogenous expression of myosin rod fragment, myosin IIA or IIB, each rod fragment blocked the proliferation of CFU-E but only the rod fragment for IIB inhibited the enucleation of mature erythroblasts. These data indicate that NMHC IIB among the isoforms is involved in the enucleation of human erythroblasts. PMID- 22049519 TI - Active vaccination with Dickkopf-1 induces protective and therapeutic antitumor immunity in murine multiple myeloma. AB - Dickkopf-1 (DKK1), broadly expressed in myeloma cells but highly restricted in normal tissues, together with its functional roles as an osteoblast formation inhibitor, may be an ideal target for immunotherapy in myeloma. Our previous studies have shown that DKK1 (peptide)-specific CTLs can effectively lyse primary myeloma cells in vitro. The goal of this study was to examine whether DKK1 can be used as a tumor vaccine to elicit DKK1-specific immunity that can control myeloma growth or even eradicate established myeloma in vivo. We used DKK1-DNA vaccine in the murine MOPC-21 myeloma model, and the results clearly showed that active vaccination using the DKK1 vaccine not only was able to protect mice from developing myeloma, but it was also therapeutic against established myeloma. Furthermore, the addition of CpG as an adjuvant, or injection of B7H1-blocking or OX40-agonist Abs, further enhanced the therapeutic effects of the vaccine. Mechanistic studies revealed that DKK1 vaccine elicited a strong DKK1- and tumor specific CD4+ and CD8+ immune responses, and treatment with B7H1 or OX40 Abs significantly reduced the numbers of IL-10-expressing and Foxp3+ regulatory T cells in vaccinated mice. Thus, our studies provide strong rationale for targeting DKK1 for immunotherapy of myeloma patients. PMID- 22049520 TI - Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies. AB - Heparin is a widely used anticoagulant. Because of its negative charge, it forms complexes with positively charged platelet factor 4 (PF4). This can induce anti PF4/heparin IgG Abs. Resulting immune complexes activate platelets, leading to the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). HIT requires treatment with alternative anticoagulants. Approved for HIT are 2 direct thrombin inhibitors (DTI; lepirudin, argatroban) and danaparoid. They are niche products with limitations. We assessed the effects of the DTI dabigatran, the direct factor Xa-inhibitor rivaroxaban, and of 2-O, 3-O desulfated heparin (ODSH; a partially desulfated heparin with minimal anticoagulant effects) on PF4/heparin complexes and the interaction of anti-PF4/heparin Abs with platelets. Neither dabigatran nor rivaroxaban had any effect on the interaction of PF4 or anti-PF4/heparin Abs with platelets. In contrast, ODSH inhibited PF4 binding to gel-filtered platelets, displaced PF4 from a PF4-transfected cell line, displaced PF4/heparin complexes from platelet surfaces, and inhibited anti-PF4/heparin Ab binding to PF4/heparin complexes and subsequent platelet activation. Dabigatran and rivaroxaban seem to be options for alternative anticoagulation in patients with a history of HIT. ODSH prevents formation of immunogenic PF4/heparin complexes, and, when given together with heparin, may have the potential to reduce the risk for HIT during treatment with heparin. PMID- 22049521 TI - Improving fitness and reducing obesity in preschool children. PMID- 22049522 TI - American legislative exchange council. PMID- 22049524 TI - Warfarin. PMID- 22049523 TI - Is journalism the drug industry's new dance partner? PMID- 22049525 TI - Environmental degradation risks undermining development progress, warns report. PMID- 22049526 TI - Lost in translation. PMID- 22049527 TI - Online is not a private space. PMID- 22049528 TI - Advance advance directives. PMID- 22049530 TI - Resveratrol protects mouse embryonic stem cells from ionizing radiation by accelerating recovery from DNA strand breakage. AB - Resveratrol has elicited many provocative anticancer effects in laboratory animals and cultured cells, including reduced levels of oxidative DNA damage, inhibition of tumor initiation and progression and induction of apoptosis in tumor cells. Use of resveratrol as a cancer-preventive agent in humans will require that its anticancer effects not be accompanied by damage to normal tissue stem or progenitor cells. In mouse embryonic stem cells (mESC) or early mouse embryos exposed to ethanol, resveratrol has been shown to suppress apoptosis and promote survival. However, in cells exposed to genotoxic stress, survival may come at the expense of genome stability. To learn whether resveratrol can protect stem cells from DNA damage and to study its effects on genomic integrity, we exposed mESC pretreated with resveratrol to ionizing radiation (IR). Forty-eight hours pretreatment with a comparatively low concentration of resveratrol (10 MUM) improved survival of mESC >2-fold after exposure to 5 Gy of X-rays. Cells pretreated with resveratrol sustained the same levels of reactive oxygen species and DNA strand breakage after IR as mock-treated controls, but repaired DNA damage more rapidly and resumed cell division sooner. Frequencies of IR-induced mutation at a chromosomal reporter locus were not increased in cells pretreated with resveratrol as compared with controls, indicating that resveratrol can improve viability in mESC after DNA damage without compromising genomic integrity. PMID- 22049529 TI - SMAC mimetic (JP1201) sensitizes non-small cell lung cancers to multiple chemotherapy agents in an IAP-dependent but TNF-alpha-independent manner. AB - Inhibitors of apoptosis proteins (IAP) are key regulators of apoptosis and are inhibited by the second mitocondrial activator of caspases (SMAC). Previously, a small subset of TNF-alpha-expressing non-small cell lung cancers (NSCLC) was found to be sensitive to SMAC mimetics alone. In this study, we determined if a SMAC mimetic (JP1201) could sensitize nonresponsive NSCLC cell lines to standard chemotherapy. We found that JP1201 sensitized NSCLCs to doxorubicin, erlotinib, gemcitabine, paclitaxel, vinorelbine, and the combination of carboplatin with paclitaxel in a synergistic manner at clinically achievable drug concentrations. Sensitization did not occur with platinum alone. Furthermore, sensitization was specific for tumor compared with normal lung epithelial cells, increased in NSCLCs harvested after chemotherapy treatment, and did not induce TNF-alpha secretion. Sensitization also was enhanced in vivo with increased tumor inhibition and increased survival of mice carrying xenografts. These effects were accompanied by caspase 3, 4, and 9 activation, indicating that both mitochondrial and endoplasmic reticulum stress-induced apoptotic pathways are activated by the combination of vinorelbine and JP1201. Chemotherapies that induce cell death through the mitochondrial pathway required only inhibition of X-linked IAP (XIAP) for sensitization, whereas chemotherapies that induce cell death through multiple apoptotic pathways required inhibition of cIAP1, cIAP2, and XIAP. Therefore, the data suggest that IAP-targeted therapy using a SMAC mimetic provides a new therapeutic strategy for synergistic sensitization of NSCLCs to standard chemotherapy agents, which seems to occur independently of TNF-alpha secretion. PMID- 22049531 TI - MicroRNA-1826 targets VEGFC, beta-catenin (CTNNB1) and MEK1 (MAP2K1) in human bladder cancer. AB - The Wnt/beta-catenin (CTNNB1) and Ras-Raf-MEK-ERK signaling pathway play an important role in bladder cancer (BC) progression. Tumor-suppressive microRNAs (miRNAs) targeting these cancer pathways may provide a new therapeutic approach for BC. We initially identified miRNA-1826 potentially targeting CTNNB1, VEGFC and MEK1 using several target scan algorithms. Also 3' untranslated region luciferase activity and protein expression of these target genes were significantly downregulated in miR-1826-transfected BC cells (J82 and T24). The expression of miR-1826 was lower in BC tissues and inverse correlation of miR 1826 with several clinical parameters (pT, grade) was observed. Also the expression of miR-1826 was much lower in three BC cell lines (J82, T24 and TCCSUP) compared with a normal bladder cell line (SV-HUC-1). We then performed analyses to look at miR-1826 function and found that miR-1826 inhibited BC cell viability, invasion and migration. We also found increased apoptosis and G(1) cell cycle arrest in miR-1826-transfected BC cells. To examine whether the effect of miR-1826 was through CTNNB1 (beta-catenin) or MEK1 knockdown, we knocked down CTNNB1/MEK1 messenger RNA using a small interfering RNA (siRNA) technique. We observed that CTNNB1 or MEK1 siRNA knockdown resulted in effects similar to those with miR-1826 in BC cells. In conclusion, our data suggest that the miR-1826 plays an important role as tumor suppressor via CTNNB1/MEK1/VEGFC downregulation in BC. PMID- 22049533 TI - Sphingosine-1-phosphate signals the way for Cx43-mediated cardioprotection. PMID- 22049532 TI - Arrhythmogenic consequences of myofibroblast-myocyte coupling. AB - AIMS: Fibrosis is known to promote cardiac arrhythmias by disrupting myocardial structure. Given recent evidence that myofibroblasts form gap junctions with myocytes at least in co-cultures, we investigated whether myofibroblast-myocyte coupling can promote arrhythmia triggers, such as early afterdepolarizations (EADs), by directly influencing myocyte electrophysiology. METHODS AND RESULTS: Using the dynamic voltage clamp technique, patch-clamped adult rabbit ventricular myocytes were electrotonically coupled to one or multiple virtual fibroblasts or myofibroblasts programmed with eight combinations of capacitance, membrane resistance, resting membrane potential, and gap junction coupling resistance, spanning physiologically realistic ranges. Myocytes were exposed to oxidative (1 mmol/L H(2)O(2)) or ionic (2.7 mmol/L hypokalaemia) stress to induce bradycardia dependent EADs. In the absence of myofibroblast-myocyte coupling, EADs developed during slow pacing (6 s), but were completely suppressed by faster pacing (1 s). However, in the presence of myofibroblast-myocyte coupling, EADs could no longer be suppressed by rapid pacing, especially when myofibroblast resting membrane potential was depolarized (-25 mV). Analysis of the myofibroblast-myocyte virtual gap junction currents revealed two components: an early transient-outward I(to) like current and a late sustained current. Selective elimination of the I(to) like component prevented EADs, whereas selective elimination of the late component did not. CONCLUSION: Coupling of myocytes to myofibroblasts promotes EAD formation as a result of a mismatch in early vs. late repolarization reserve caused by the I(to)-like component of the gap junction current. These cellular and ionic mechanisms may contribute to the pro-arrhythmic risk in fibrotic hearts. PMID- 22049535 TI - A novel adult human ventricle slice preparation for cardiac drug discovery and safety pharmacology. PMID- 22049534 TI - Inhibition of SMAD2 phosphorylation preserves cardiac function during pressure overload. AB - AIMS: Left ventricular (LV) pressure overload leads to myocardial remodelling and reduced cardiac function. Both cardioprotective and deleterious effects have been attributed to SMAD2/3 (SMAD, small mothers against decapentaplegic) signalling, but the role of these important molecules in pressure overload remains unclear. The aim of this study was to examine the effects of SMAD2 inhibition on cardiac function and remodelling in mice subjected to aortic banding (AB), using a small molecule inhibitor (SM16) of SMAD2 signalling. METHODS AND RESULTS: C57BL/6 mice were subjected to 1 week of AB, which led to a three-fold increased phosphorylation of SMAD2 that was reduced by SM16 (P<= 0.05), as measured by western blotting. Cardiac function was evaluated by echocardiography and was preserved by SM16, as fractional shortening was increased by 38% (P<= 0.05) and mitral flow deceleration reduced by 28% compared with AB mice not receiving SM16 (P<= 0.05). In accordance with this, SM16 abolished the 21% increase in lung weight in AB mice (P<= 0.05). Cardiomyocyte hypertrophy and foetal gene expression, as measured by qPCR, were also reduced. Myocardial collagen protein was unaltered 1 week after AB. LV sarcoplasmic reticulum Ca(2+)ATPase (SERCA2) reduction in AB mice and in transforming growth factor-beta1-stimulated rat cardiomyocytes was diminished by SM16. Ca(2+) transient decay kinetics were improved in cardiomyocytes isolated from AB mice receiving SM16. CONCLUSION: In pressure overload, pharmacological inhibition of SMAD2 signalling attenuated cardiomyocyte hypertrophy and preserved cardiac function. SM16 prevented SMAD2 mediated downregulation of SERCA2 in vivo and in cardiomyocytes, suggesting improved cardiomyocyte Ca(2+) handling as a possible cardioprotective mechanism. PMID- 22049536 TI - The bittersweet of steroid therapy. PMID- 22049537 TI - Atrial fibrillation management: issues of concern (APRIL 2011). PMID- 22049538 TI - Angioedema due to the renin inhibitor aliskiren (MAY 2011). PMID- 22049539 TI - An erythematous plaque on the nose. PMID- 22049540 TI - Osborn waves: an inverse correlation with core body temperature. PMID- 22049541 TI - Cervical cancer screening: Less testing, smarter testing. AB - In its 2009 recommendations for cervical cancer screening, the American College of Obstetricians and Gynecologists (ACOG) calls for less-frequent but smarter screening that integrates testing for human papillomavirus (HPV) infection with the Papanicolaou (Pap) test. We review the recommendations from this and other organizations and how and why they are evolving. PMID- 22049542 TI - Glucocorticoid-induced diabetes and adrenal suppression: how to detect and manage them. AB - Glucocorticoids, commonly used to treat multiple inflammatory processes, can cause hyperglycemia, Cushing syndrome, adrenal suppression, and, when they are discontinued, adrenal insufficiency. Physicians must be aware of these adverse effects and be equipped to manage them. PMID- 22049544 TI - Do you get up a lot at night to go to the bathroom? PMID- 22049543 TI - Nocturia in the elderly: a wake-up call. AB - Nocturia is a condition that health providers must seek out and address in older adults. Since it adversely affects quality of life and carries a risk of morbidity and of death (often because of falling), this symptom must be elicited during the physician-patient encounter. Understanding its underlying causes, risk factors, and consequences is essential in formulating the most suitable management strategy. Drug and nondrug treatments target the individual disorders that contribute to nocturia. PMID- 22049546 TI - Hints of exo-Earths spark desire for a closer look. PMID- 22049545 TI - Texas prepares to fight for stem cells. PMID- 22049547 TI - Education: time to teach. PMID- 22049548 TI - Retraction notice to "Synthesis and biological evaluation of [1,2,4]triazino[4,3 a] benzimidazole acetic acid derivatives as selective aldose reductase inhibitors" [Eur. J. Med. Chem. (2010) 909-914]. PMID- 22049549 TI - David R. Bowsher, M.D., Sc.D., Ph.D., FRCPEd., FRCPath., 1925-2011. PMID- 22049550 TI - Design, synthesis, and evaluation of 5'-diphenyl nucleoside analogues as inhibitors of the Plasmodium falciparum dUTPase. AB - Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5'-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Modelling studies indicated that it might be possible to replace the trityl group with a diphenyl moiety, as two of the phenyl groups are buried, whereas the third is exposed to solvent. Herein we report the synthesis and evaluation of some diphenyl analogues that have lower lipophilicity and molecular weight than the trityl lead compound. Co-crystal structures show that the diphenyl inhibitors bind in a similar manner to the corresponding trityl derivatives, with the two phenyl moieties occupying the predicted buried phenyl binding sites. The diphenyl compounds prepared show similar or slightly lower inhibition of PfdUTPase, and similar or weaker inhibition of parasite growth than the trityl compounds. PMID- 22049551 TI - Effects of water molecules on photoluminescence from hierarchical peptide nanotubes and water probing capability. AB - Photoluminescence (PL) spectra reveal that deficiency of water molecules in the channel cores of bioinspired hierarchical diphenylalanine ( L -Phe- L -Phe, FF) peptide nanotubes (PNTs) not only modifies the bandgap of the subnanometer crystalline structure formed by the self-assembly process, but also induces a characteristic ultraviolet PL peak the position of which is linearly proportional to the number of water molecules in the PNTs. Addition or loss of water molecules gives rise to the UV PL redshift or blueshift. Density functional theory calculation also confirms that addition of water molecules to the PNTs causes splitting of the valence-band peak, which corresponds to the shift and splitting of the observed UV PL peak. Water molecules play an important role in the biological properties of FF PNTs and the results demonstrate that the PL spectra can be used to probe the number of water molecules bonded to the FF molecules. PMID- 22049552 TI - Acupuncture still popular. PMID- 22049553 TI - Senator Mark O. Hatfield: an advocate for sleep. PMID- 22049554 TI - [The 150th birthday of Karl Herxheimer]. PMID- 22049555 TI - Who invented and used this curious bistoury? PMID- 22049556 TI - Prion proteins. PMID- 22049558 TI - Patient involvement in preoperative marking. PMID- 22049557 TI - On the Horizon: Europe's next round of science funding. PMID- 22049559 TI - The patient with vertigo. Evaluation of the dizzy patient can pose challenges in the prehospital setting. PMID- 22049560 TI - Your chance to shine. AB - The core panel judges of the Nursing Standard Nurse Awards 2012 invite entrants to spell out their achievements. The winners will be innovators who have made a real difference to their patients. PMID- 22049580 TI - "Shovelling out your paupers": the British state and Irish famine migration, 1846 50. PMID- 22049581 TI - State, civil society and separation in Victorian marriage. PMID- 22049582 TI - Re-engineering drug discovery and development. AB - The rate of new drug approvals in the US has remained essentially constant since 1950, while the costs of drug development have soared. Many commentators question the sustainability of the current model of drug development, in which large pharmaceutical companies incur markedly escalating costs to deliver the same number of products to market. This Issue Brief summarizes the problem, describes ongoing governmental efforts to influence the process, and suggests changes in regulatory science and translational medicine that may promote more successful development of safe and effective therapeutics PMID- 22049583 TI - The double standard revisited: Plebeian women and male sexual reputation in early modern England. PMID- 22049584 TI - The early modern Japanese state and Ainu vaccinations: redefining the body politic, 1799-1868. PMID- 22049585 TI - The fate of a generation. PMID- 22049586 TI - The hideous trade: economic aspects of the "manufacture" and sale of eunuchs. PMID- 22049588 TI - The Sunday-school movement in England and Wales: child labour, denominational control and working-class culture. PMID- 22049587 TI - The International Working Men's Association (1864-1876) and workers' education: an historical approach. PMID- 22049589 TI - Waging war on children and youth through schooling disruption. PMID- 22049590 TI - What do literacy rates in the 19th century really signify? New light on an old problem from unique Swedish data. PMID- 22049591 TI - Appropriate attribution. PMID- 22049592 TI - STDs: Drug resistance demands dual therapy. PMID- 22049593 TI - Anglo-American town planning theory since 1945: three significant developments but no paradigm shifts. PMID- 22049594 TI - Avoiding the mistakes of the "mother country": the New Zealand garden city movement, 1900-1926. PMID- 22049595 TI - Ethnic cleansing in Silesia 1950-89 and the ennationalizing policies of Poland and Germany. PMID- 22049596 TI - Evolutionary dynamics of urban land use planning and environmental sustainability in Nigeria. PMID- 22049597 TI - [Family, women, and the relations of the sexes in Latin America]. PMID- 22049598 TI - From regulation to discretion: the evolution of development control in the British planning system, 1909-1947. PMID- 22049599 TI - From westernisation to globalisation: an old district of Istanbul. PMID- 22049600 TI - Governments, consultants and expert bodies in the physical reconstruction of the City of London in the 1940s. PMID- 22049601 TI - From hospital to home: how will equipment and care evolve? PMID- 22049602 TI - From the user's perspective: home health nurses share insights. PMID- 22049603 TI - Design considerations for medical devices in the home environment. AB - Patient demographics, economic forces, and technological advancements contribute to the rise in home care services. Advanced medical devices and equipment originally designed for use by trained personnel in hospitals and clinics are increasingly migrating into the home. Unlike the clinical setting, the home is an uncontrolled environment with additional hazards. The compatibility of the device with the recipient's knowledge, abilities, lifestyle, and home environment plays a significant role in their therapy and rehabilitation. The advent of new device technologies such as wireless devices and interoperability of systems lends a new and complex perspective for medical device use in the home that must also be addressed. Adequately assessing and matching the patient and their caregiver with the appropriate device technology while considering the suitability of the home environment for device operation and maintenance is a challenge that relies on good human factors principles. There is a need to address these challenges in the growing home care sector In this article, the authors take a look at some important considerations and design issues for medical devices used in the home care environment. PMID- 22049604 TI - Highlights of the new international standard on home healthcare devices. AB - In this article, leaders of the joint working group that developed a new international standard for medical equipment used in the home healthcare environment report on key provisions of the standard. A new AAMI committee is now considering adopting it as an American National Standard. PMID- 22049605 TI - Human factors in labeling and training for home healthcare technology. AB - In this article, Patricia A. Patterson, a contributor to the recently-released standard ANSI/AAMI HE75:2009 Human factors engineering-Design of medical devices, highlights information from the standard important to developing labeling and training for homecare devices. She also describes one approach to developing labeling and training materials. PMID- 22049606 TI - Simple, interoperable, wireless connectivity solutions for home healthcare. PMID- 22049607 TI - The hospital at home: advances in remote patient monitoring. PMID- 22049608 TI - Continua health alliance aims for interoperable personal health solutions. PMID- 22049609 TI - Home healthcare: the next BMET frontier. PMID- 22049610 TI - A natural fit: home healthcare and biomedical engineering. AB - The involvement of Biomed in management of home care equipment has become a natural fit for Rady Children's Hospital. Managing all aspects of home care equipment through an in-house biomedical engineering department is cost effective, efficient, provides excellent customer service, and enhances the relationship with the clinical staff and patients. It develops a sense of security for patients and staff that home care equipment is tested and maintained in a stringent manner that promotes safety. PMID- 22049611 TI - Service models for remote healthcare monitoring systems. AB - These scenarios reflect where the future is heading for remote health monitoring technology and service expectations. Being able to manage a "system of systems" with timely service hand-off over seams of responsibility and system interfaces will become very important for a BMET or clinical engineer. These interfaces will include patient homes, clinician homes, commercial/civilian infrastructure, public utilities, vendor infrastructure as well as internal departmental domains. Concurrently, technology is changing rapidly resulting in newer software delivery modes and hardware appliances as well as infrastructure changes. Those who are able to de-construct the complex systems and identify infrastructure assumptions and seams of servicing responsibility will be able to better understand and communicate the expectations for service of these systems. Moreover, as identified in Case 1, prodigious use of underlying system monitoring tools (managing the "meta-data") could move servicing of these remote systems from a reactive approach to a proactive approach. A prepared healthcare organization will identify their current and proposed future service combination use cases and design service philosophies and expectations for those use cases, while understanding the infrastructure assumptions and seams of responsibility. This is the future of technical service to the healthcare clinicians and patients. PMID- 22049612 TI - AAMI blood pressure device standard targets home use issues. AB - In this article, leaders of the AAMI Sphygmomanometer Committee report on their efforts to address home use issues in standards for blood pressure devices, and the importance of standards to ensuring safety and effectiveness of home use devices. PMID- 22049613 TI - Reengineering hemodialysis for the home environment. AB - Denny Treu of NxStage Medical, Inc., who has led the development of six dialysis systems with various companies, reports here on a home hemodialysis system that his company successfully designed specifically for home use. PMID- 22049614 TI - Home healthcare: it's about the patient, and the caregiver. PMID- 22049615 TI - The bone marrow stem stromal imbalance--a key feature of disease progression in case of myelodysplastic mouse model. AB - Myelodysplastic syndromes (MDSs) represent a spectrum of disorders that are generally thought to arise from a defective hematopoietic stem cell leading to clonal, dysregulated hematopoiesis. Although it is generally agreed that the marrow microenvironment plays a role in the biology of MDS, it is unclear whether this represents an intrinsically abnormal stromal compartment derived from the MDS clone. Hematopoiesis requires cooperation between progenitors and a variety of functionally and phenotypically different cell types that form the bone marrow stroma. Stromal abnormalities suspected to contribute to the pathology of bone marrow disorder with impaired hematopoiesis. Several studies on human MDS bone marrow microenvironment revealed functional alteration and increased cellular apoptosis thus contribute to the pathology of the disease progression. In this present study, we have investigated alterations in the hematopoietic microenvironment and underlying mechanisms involved in the disease progression of MDS animal model. We presented the results of bone marrow single cell culture study, Long-term bone marrow adherent culture study (LTBMC) and their functional efficacy, flowcytometric characterization of stem (Scal+c-kit+) and stromal (Scal+CD44+) progenitor cell population and expression level of extracellular apoptosis marker (Annexin v) in the bone marrow cells of MDS animal model. Bone marrow single cell culture study of MDS animal showed impairment in the normal cellular generation, proliferation and presence of apoptic cells. Long-term liquid Bone marrow stromal cell colony formation assay from MDS bone marrow cells showed significant difference in the colony formation and their maintenance than the control groups of animals. Immune functional capacity of the bone marrow stromal cells through cell mediated immune (CMI) parameter study denoted defects in the stromal microenvironment. Decreased expression of bone marrow long-term primitive hematopoietic population and stromal progenitor population depicted bone marrow abnormality in case of MDS animal model, which bears significant correlation with high expression level of apoptosis marker in the bone marrow cells. From the above experimental study we tried to highlight the abnormal bone marrow microenvironment and alteration in the bone marrow cell surface marker expression, which could be the probable mechanism of evolution and disease progression in case of MDS animal model. PMID- 22049616 TI - Sca-1 expression pattern in the mouse limbal epithelium and its association with cell cycle. AB - Stem Cell Antigen-1 or Sca-1 is a cell surface receptor protein commonly used to detect adult murine haematopoietic stem cell population. Outside the haematopoietic system Sca-1 is similarly expressed in stem and progenitor cells in a wide variety of tissues and organs such as skeletal muscle, mammary gland, prostate, heart, liver and dermis. Thus Sca-1 has become a candidate marker in the search of tissue specific stem cells. The maintenance of a healthy corneal epithelium is achieved by a unique population of stem cell located in the limbal epithelial region. This limbal epithelium mainly contains limbal epithelial stem cells and its immediate progenitor early transient amplifying cells (e-TAC) which have self renewal capacity. As stem cells in other organs have been identified by their expression of Sca-1, in our study we wanted to determine whether this antigen could be present in the limbal epithelial region which contains stem cell population by using immunofluorescence through flow cytometric analysis of Sca-1 and its association with the cell cycle. PMID- 22049617 TI - Isolation, characterization and mobilization of prostate cancer tissue derived CD133+ MDR1+ cells. AB - Cancer stem cells undoubtedly exist in many tumor types, including the prostate. CD133 has recently been considered an important marker that represents the subset population of cancer stem cells. The purpose of the present study is to isolate CD133+ and CD133- cells from normal healthy volunteers and prostate cancer patients to check the prostate stem cells markers and chemokine receptors like CXCR4 for their mobilization. In this study we isolated CD133+ and CD133- cells using magnetic beads from prostate tissues and peripheral blood samples of normal healthy volunteers and prostate cancer patients (NV-CD133+, NV-CD133-, PC-CD133+ and PC-CD133-). The isolated cells were analyzed using flow cytometry and western blot analysis of MDR1, alpha2beta1, CD44, Oct-4 and CXCR4. PC-CD133+ cells displayed higher expressions of CD44, MDR1, Oct-4 and alpha2beta1 expressions with the ability to differentiate into prostate cancer cells. Furthermore, PC CD133+, highly expressed the chemokine receptor CXCR4 and its ligand SDF1-alpha. Here we conclude that, PC-CD133+ displayed a higher expression of prostate stem cell markers like CD44, MDR1 and Oct-4 and chemokine receptor CXCR4 and its ligand SDF1-alpha in peripheral blood and prostate cancer tissue derived CD133+ cells The CXCR4 and SDF1-alpha expressions will have impact on the mobilization of prostate cancer stem cells (PC-CD133+ cells). PMID- 22049618 TI - Placental membrane as a source of mesenchymal stem cells. AB - Non-embryonic stem cells have the potential for being used in therapeutic attempts to develop treatments for human diseases and injuries. There is an increasing demand for non invasive treatments for a number of diseases and disorders that strike and disable relatively young people that would otherwise have many active years ahead. As longevity increases and we face new challenges in treating patients who suffers from disorders that reduces their quality of life already at middle age. Simple, secure methods to isolate non-embryonic stem cells from different tissues is one step towards making those treatments available to people suffering from Parkinson's disease, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis. PMID- 22049619 TI - Establishment of a brain tumor tissue repository in India: maintaining quality standards. AB - Tumor tissue repositories (TTRs) play a pivotal role in both basic and translational research by acting as a conduit to facilitate innovative research, thereby providing solutions to treat the incurable disease--'Cancer'. One of the fundamental requirements to achieve this goal would be the acquisition of high quality tumor tissue specimens that are stored in such a manner that its integrity is preserved. Further, a quality system should be in place that assures the compliance of procedures that are the key to a smooth functioning of all the inter-related departments that play a key role in the entire operations. To address this, we have initiated an effort to build a tumor tissue repository of brain tumor tissues in the Southern part of the Indian sub-continent. One of the cardinal features of brain tumors is the heterogeneity, both phenotypically and genotypically. Moreover, significant gaps exist in current understanding of the molecular pathways involved in the genesis, progression, and biological and clinical behavior of brain tumors. We hope that our initiative will provide researchers accessibility to a reserve of high quality tissues in this part of the globe. We have created and validated a complete histology service including tissue processing, embedding, sectioning and H&E staining for fixed tissues, in addition to creating and staining frozen sections. To our knowledge, such a structured initiative to store brain tumor samples is the first of its kind in the India. PMID- 22049620 TI - Kilimanjaro through the keyhole. AB - Amanda Parkin, marketing manager at approved design and build consultant to the NHS for integrated theatres and digital video communications, OR Networks, explains how, with the help of the company and its specialist equipment, Northumbrian surgeons successfully established a two-way audio/video link to their counterparts at a hospital in the foothills of Mount Kilimanjaro to enable them to train the Tanzanian surgeons in laparoscopic surgery. Alongside opening up many new teaching opportunities in both the UK and Tanzania, the link-up has already saved countless lives. PMID- 22049621 TI - Making hospital water safe, examined. AB - What are the best methods for monitoring hospital water systems to prevent contamination by waterborne pathogens such as Pseudomonas aeruginosa and Legionella? How can hospital staff determine whether a Pseudomonas outbreak is due to cross-contamination between patients and staff, or to the contamination of a systemic water supply, and how can we best protect our most vulnerable patients from infection with the array of pathogenic organisms lurking in hospitals? As Susan Pearson reports, these were among the questions discussedby leading microbiologists at a recent one-day "waterborne infections" seminar organised by Pall Medical in Glasgow. PMID- 22049622 TI - Managing EMC within healthcare facilities. AB - Damon High, a consultant at international testing, certification, qualification, training, and consultancy services provider TUV Product Service, examines the issue of electromagnetic interference in hospitals, highlighting the areas that equipment suppliers and estates and facilities managers/healthcare engineers need to consider to ensure both the continuing safe, reliable operation of equipment, and compliance with the latest legislation. PMID- 22049623 TI - Turnkey offering a claimed sector 'first'. AB - Manufacturer and supplier of LED theatre lights, HD camera systems, video integration technologies, and ceiling support units, Trumpf Medical Systems UK, and "logistical services" company Canute International Medical Services (CIMS), one of whose specialities is providing mobile medical units for diagnostic imaging, have entered into a partnership that will see the two companies offer fully fitted out modular operating theatres and other medical/clinical buildings incorporating the latest technology and equipment, on a fully project-managed, "turnkey" basis. Oliver Law, Trumpf Medical Systems UK managing director, explains the background, and the new service's anticipated customer benefits. PMID- 22049624 TI - Performance. DH chases up service changes an undisguised urgency. PMID- 22049625 TI - Outlook worsens for challenged acute trusts. PMID- 22049626 TI - John Oldham intolerance of incompetence. PMID- 22049627 TI - Fix the system to find the finances. PMID- 22049628 TI - Andrew Burnell on the big bland offer. PMID- 22049629 TI - Mental health. Raising the bar on police custody. PMID- 22049630 TI - Care pathways. The full package of pneumonia care. PMID- 22049631 TI - Learning. All aboard for better services. PMID- 22049632 TI - Patient's perspective and an analytical gaze which regards communicative activities. PMID- 22049633 TI - Halting aphasic interaction: creation of intersubjectivity and spousal relationship in situ. AB - This article discusses a communicative phenomenon that is relatively less studied: getting stuck in an aphasic conversation. Although aphasia as a medical and linguistic condition has been widely examined, the more social and participatory aspects of the symptom are not so well-known. Aphasia forms a threat to the emergence of a shared understanding, as well as to the experience of being in the shared, i.e., in the intersubjective, social world. In our analysis, we closely explore how understanding is constructed in the sequential organization of conversation. We use two data corpora when analysing the halting interaction. In our data, we detected two kinds of interactive halts that emerged in connection with aphasic word searching. First, 'real halts' were caused by the aphasic person's inability to find correct words and the co-participants were also not able to resolve the problem. Second, 'exam halts' occurred when the co participant did not provide the missing words despite knowing what the aphasic speaker was trying to say. We discuss how this halting phenomenon is linked with the notions of intersubjectivity and face-work and conclude that real halts are more directly caused by the aphasic condition, whereas exam halts reflect the spousal relationship in the form of face-work. PMID- 22049634 TI - Coping with chronic illness: information use and treatment adherence among people with diabetes. AB - This study's goal is to understand the complex relationship among information usage, medication adherence, and disease management in people with diabetes. Toward this end, we conducted 21 in-depth interviews with Type 2 diabetics. We queried patients on the sources and adequacy of information that they received about their disease, as well as on how closely they adhered to their prescribed medication regimen. Interviewees identified 12 sources of information that they used to varying degrees in managing their diabetes. Of these sources, patients relied most heavily on their doctors, particularly upon initial diagnosis, in spite of delivering mixed assessments of the adequacy of their physicians'provision of information. Other sources patients most frequently discussed included diabetes education programs, friends/family, the internet, the information leaflet that accompanies prescriptions and written information. Further, those who reported high adherence to their treatment regimen tended to rely on different sources than those who reported low adherence. Findings are interpreted within the framework of the Health Belief Model, and implications for designing effective interventions are discussed. PMID- 22049635 TI - Positioning identity in clinical interviews with people who stutter. AB - Clinicians often rely on ethnographic interviews to make judgments about the effect of stuttering on the lives of people who stutter. This form of interview aids the clinician in assessing specific dimensions of the client's life (e.g. career choice, education, etc.) that might be impacted by dysfluency. Further, the information gathered from ethnographic interviews is used to make professional judgments relating to the client's personality type and behavioral traits. This study used methods associated with discursive psychology to examine data taken from two ethnographic interviews between a clinician and two people who stuttered. The interviews were semi-structured and used probe questions to elicit the participants' viewpoints about the effects of stuttering on their lives. Data taken from the interviews were then examined to investigate the subject positions participants discursively aligned to within their accounts. We discuss the implications of making clinical judgments regarding a client's identity from such interviews. PMID- 22049636 TI - Patient involvement in problem presentation and diagnosis delivery in primary care. AB - This article reports a conversation analytic study of primary care physicians' orientations to different types of patients' problem presentation. Four types of problem presentation are examined: 1. symptoms only; 2. candidate diagnosis; 3. diagnosis implicative symptom description; and 4. candidate diagnosis as background information. The analysis shows that both in receiving the problem presentation at the beginning of the visit and in delivering a diagnosis later on, doctors address the patients' presentations which involved or implied a candidate diagnosis. In contrast, following a symptoms-only type of problem presentation such references predominantly are not made. The study suggests that patients' problem presentation have a crucial role in shaping the doctor's communication patterns also in the phases of consultation in which the patient's active participation is of lesser significance, such as the diagnostic phase. The findings are discussed in relation to the question of patient participation in the medical consultation. The data consist of 86 video-recorded Finnish primary care consultations for upper respiratory tract infection including both child and adult patients. PMID- 22049637 TI - Collaborative work and medical talk: opportunities for learning through knowledge sharing. AB - Teleconsultations provide new opportunities for learning in medical settings. This study explores the conditions under which learning among physicians takes place. The empirical context is 47 real-time video conferences carried out to examine collaborative work and the medical talk involved. Sixteen of the observations were consultations wherein general practitioners (GPs) and specialists shared knowledge with the purpose of solving a medical problem related to a patient under treatment. In this exploratory study, the learning opportunities are seen as what medical practitioners with different types of expertise achieve through interaction while working with patients over periods of time. The analysis of medical talk in consultations shows that collaborative work among GPs and specialists creates a shared understanding of the patient's clinical history and treatment trajectory. As knowledge is demanded and attributed and gaps of knowledge become shared, consultations create a work tool that expands the medical work and talk. Collaborative work in and between different levels of the health care service expands knowledge, creates opportunities for learning in everyday settings, and improves the quality of knowledge distribution in the health care system. PMID- 22049638 TI - How care providers construct and frame problems related to violence in institutional care for older people. AB - The aim of the present study was to describe how care providers discursively constructed and framed problems related to the occurrence of violence in their interactions with older persons in institutional care. The study followed a social constructionist approach where violence was considered a social phenomenon constructed in discursive processes. It was based on the assumption that in the way in which a problem is articulated is closely connected to solutions that are possible and relevant in a given context. The analysed corpus comprised narrative interviews with 46 care providers who had been involved in violence that occurred in social interactions with older persons. The analysis was inspired by discourse theory. The problems concerned legitimization, illness, bodily care, competence and profession and relieved responsibility. The constructions of the problems are manifestations of discourses. The prevailing discourses in the text are the medical and the physical. The construction of problems can be used to challenge dominant ways of thinking as well as the beliefs and common understandings about the subject. PMID- 22049639 TI - The role of active participation in interaction for children who use augmentative and alternative communication. AB - The present case-study investigates practices in interaction that manifest themselves as active participation for three Swedish children who use augmentative and alternative communication (AAC). Analyses are based on interaction data from three different settings, involving the children in dialogue with adults as well as peers. In-depth analysis of the data by means of Conversation Analysis revealed three practices conducive for active participation. The first one dealt with experiencing a sense of control, i.e. that the child who uses AAC was treated as a competent communicator, e.g. initiating topics and allocating turns, etc. The second practice revealed the importance of co-construction of communicative projects, and the possible negative effects of instances where adults attempted to impose an agenda on the children. Finally, analyses displayed different means by which participants could be included in the interaction, and the effects of such strategies. The study stresses the importance of communication partners' abilities to balance and counterbalance the necessity to follow, share or sometimes inhibit a need to shape contributions to interaction, in order to enhance active participation for the child who uses AAC. PMID- 22049640 TI - Use of metaphors in motivational interviewing sessions in the probation service. AB - This paper examines the use of metaphors in client-counsellor interaction in motivational interviewing counselling sessions in the context of probation service. Clients who participated in these counselling sessions and in this study had either an alcohol or drug abuse problem. My aim is to show how the interaction between the client and counsellor is shaped by reciprocal use of metaphors, and how the client's change-talk finds expression in metaphorical utterances. In these counselling sessions, the use of metaphors occurred in five interactional configurations: 1. participants work with and develop together shared metaphors; 2. the client accepts the counsellor's metaphorical description but does not use it himself/ herself; 3. either the client or the counsellor suggests an alternative metaphor; 4. the counsellor systematically ignores the client's metaphor; and 5. the counsellor does not understand the meaning of the client's metaphor. The analysis suggests that metaphorical utterances play a major part in the interaction between the client and the counsellor and in the client's change-talk. These findings support the notion that metaphor and change are closely linked, and a metaphor may act as a vehicle of change. PMID- 22049641 TI - When trustworthiness matters: how trust influences knowledge-production and knowledge-sharing in a surgical department. AB - Transferring clinical knowledge and bringing various representations of clinical knowledge together is crucial as support for clinical decision-making. While previous scholarship has elaborated patients' trust of healthcare providers as well as the healthcare system, this article emphasizes trust as a catalyst for clinical knowledge production. Using an observational study of a surgical department at a large Norwegian hospital, the article focuses on knowledge transfer between surgeons in a surgical department. The surgeons' confidence to initiate knowledge requests and the perceived trustworthiness of knowledge by colleagues is significant. There is a distinct underuse of medical patient records, both paper-based and electronic, which results in an oral transferring and sharing of clinical knowledge. Significantly this oral knowledge-transfer is dynamic and effective, meeting demands for timely patient information. By studying knowledge-intensive work very closely from a perspective that suggests that knowledge is local and developed through trust and dependence, this study identifies how work practices have developed to be effective with little support of formal information systems. PMID- 22049642 TI - Talk about values in the British National Health Service. PMID- 22049643 TI - Distress after a single violent crime: how shame-proneness and event-related shame work together as risk factors for post-victimization symptoms. AB - To increase understanding of post-victimization symptom development, the present study investigated the role of shame- and guilt-proneness and event-related shame and guilt as potential risk factors. 35 individuals (M age = 31.7 yr.; 48.5% women), recently victimized by a single event of severe violent crime, were assessed regarding shame- and guilt-proneness, event-related shame and guilt, and post-victimization symptoms. The mediating role of event-related shame was investigated with structural equation modeling (SEM), using bootstrapping. The guilt measures were unrelated to each other and to post-victimization symptoms. The shame measures were highly intercorrelated and were both positively correlated to more severe post-victimization symptom levels. Event-related shame as mediator between shame-proneness and post-victimization symptoms was demonstrated by prevalent significant indirect effects. Both shame measures are potent risk factors for distress after victimization, whereby part of the effect of shame-proneness on post-victimization symptoms is explained by event-related shame. PMID- 22049644 TI - Sex differences in sympathy for attempted suicides. AB - In a sample of 115 undergraduates, women expressed more sympathy for hypothetical attempted suicides than did men, but not more empathy or agreement with the actions. A history of considering suicide was not associated with judgments about attempting suicide. PMID- 22049645 TI - Cross-national measure of fear-based xenophobia: development of a cumulative scale. AB - To apply a Mokken Scale Procedure in developing a hierarchical cross-national scale to measure xenophobia, a pool of 30 xenophobia-related items was collected from several sources and modified using established unidimensional criteria. The survey was administered to 608 undergraduate students in the USA, 193 undergraduate students in The Netherlands, and 303 undergraduate students in Norway. 14 items measuring perceived threat or fear and meeting the criteria of the Stereotype Content Model were selected for further analysis. A separate item analysis and, subsequently, Mokken Scale Procedure yielded a cumulative scale with the same five items for each of the three samples. The items and the total scale met criteria for homogeneity in all samples with H > .40. PMID- 22049646 TI - Meehl's "crud" factor, subjective wellbeing, and religiosity: a critique'. AB - Researchers in the area of subjective wellbeing are now building on a body of research that spans more than three decades and includes many thousands of articles. It is time to move from exploratory studies to those based on accumulated psychometric understanding and theory. Two aspects of the article by Abdel-Khalek (2011) warrant attention from this perspective: the choice of scale and the issue of shared variance. PMID- 22049647 TI - Chilean validation of the Posttraumatic Stress Disorder Checklist-Civilian version (PCL-C) after the earthquake on February 27, 2010. AB - Posttraumatic stress disorder (PTSD) is an anxiety disorder in which an individual re-experiences a traumatic event, avoids situations related to it, and shows excessive arousal. The disorder appears after experiencing a life threatening event, such as a war or a natural disaster. Thus, the validation of tests which assess the disorder after the earthquake on February 27, 2010, in Chile is crucial for its evaluation and subsequent intervention. The present study includes psychometric data for the Posttraumatic Stress Disorder Checklist Civilian version (PCL-C) on a sample of 509 survivors of the disaster. Values indicate good psychometric properties of the questionnaire. PMID- 22049648 TI - Cognitive styles in an international perspective: cross-validation of the Cognitive Style Indicator (CoSI). AB - This study examines the cross-cultural validity of the Cognitive Style Indicator (CoSI). Measurement equivalence tests were performed on data collected from a Belgian (n = 300) and a South African (n = 246) sample of students and employees. Confirmatory factor analyses within each sample showed the best fit to the data for a three-factor model underlying the CoSI. Measurement invariance tests, using multigroup confirmatory factor analysis, indicated that the relationships among the scales showed equivalence across cultures. Although the study is an important first step toward the cross-validation of the CoSI, further research in other international samples is particularly needed to strengthen these results. PMID- 22049649 TI - A text analysis of the poems of Sylvia Plath. AB - Changes in the words used in the poems of Sylvia Plath were examined using the Linguistic Inquiry and Word Count, a computer program for analyzing the content of texts. Major changes in the content of her poems were observed over the course of Plath's career, as well as in the final year of her life. As the time of her suicide came closer, words expressing positive emotions became more frequent, while words concerned with causation and insight became less frequent. PMID- 22049650 TI - Psychometric properties and factor structure of the Greek version of the Cardiac Anxiety Questionnaire (CAQ). AB - The present study assesses the psychometric properties and factor structure of the Greek version of the Cardiac Anxiety Questionnaire (CAQ). The questionnaire was administered to 598 healthy individuals from 15 different regions of Greece with a measure of socioeconomic characteristics and the Symptom Checklist-90 Revised (SCL-90-R). The sample was split into two random halves, and exploratory factor analysis indicated a three-factor solution. This solution was tested using a confirmatory factor analysis on the second half of the sample. In terms of latent dimensions, the Greek version retains the three-factor structure as proposed by the initial authors. However, adequate fit was achieved only after omitting eight items. The shorter (10-item) version was submitted to further analysis. The shorter version provided satisfactory internal reliability and evidence indicating the validity of the scale with respect to SCL-90-R subscales. The stability of the questionnaire was verified by a high test-retest reliability over a 3-mo. period (r = .86). Sex and age differences were assessed. The 10-item version appears to be a practical, brief tool for clinical use. PMID- 22049651 TI - Psychosocial responses associated with perceived risk of cancer in an African American community. AB - This epidemiologic health survey study examined the association between health risk perceptions and psychosocial factors in 145 African Americans in East Montgomery, Alabama. The survey gathered information on demographics, population dynamics, health risk perceptions, and coping behaviors. Psychosocial variables measured were worries, concern, stress, and trauma associated with perceived risk of cancer. Results indicated that women were more concerned about the environmental health risks in their community than men. Compared to men, women were highly concerned about the economic effect of perceived environmental health risk. The findings indicate that an individual's health status and educational level were significant predictors of psychosocial responses. PMID- 22049652 TI - Different attitudes toward humor between Chinese and American students: evidence from the Implicit Association Test. AB - Although cross-cultural research indicates that Chinese people demonstrate less humor than do Americans, little research addresses the reasons. This cross cultural difference may be largely due to different implicit attitudes toward humor held by Chinese and Americans, deeply rooted in the two cultural traditions. Both self-report evaluation and the Implicit Association Test (IAT) were used to compare Chinese and American attitudes toward humor. Although 60 Chinese undergraduate students showed no significant difference from 33 American exchange students in explicit attitudes toward humor, the former associated humor more frequently with unpleasant adjectives and seriousness with pleasant adjectives on the IAT; the opposite pattern was found for the American group. This indicated a negative implicit attitude toward humor among the Chinese students. PMID- 22049653 TI - Eating-related Intrusive Thoughts Inventory: exploring the dimensionality of eating disorder symptoms. AB - The aims of this study were, first, to examine the structure and validity of the Eating-related Intrusive Thoughts Inventory (INPIAS), a self-report questionnaire designed to assess eating disorders related to intrusive thoughts (EDITs), and second, to explore the existence of a continuum ranging from normal to abnormal thought intrusions related to eating, weight, and shape. Participants were 574 (408 women) nonclinical community individuals. Analyses revealed that EDITs can be clustered into three sets: appearance-dieting, need to exercise, and thoughts impulses related to eating disorders. EDITs' consequences showed a two-factor structure: emotional consequences/personal meaning and thought-action fusion responsibility; and four factors of strategies: "anxiety," suppression, obsessive compulsive rituals, and distraction. The sample was then divided according to reported restrained eating. The High dietary restraint group reported a higher frequency of EDITs, whereas differences in the other factors were mediated by depression, anxiety, and obsessionality. The results suggest that eating disorder related cognitions are experienced by nonclinical individuals, and distributed on a continuum. PMID- 22049654 TI - Negative moderating effect of general self-efficacy on the relationship between need for cognition and cognitive effort. AB - This study demonstrates the negative moderating effect of general self-efficacy on the relationship between need for cognition, which refers to stable individual differences in people's tendencies to engage in and enjoy cognitive activity, and cognitive effort. This negative moderating effect of general self-efficacy has been termed "plasticity." Scholars assume the relationship between need for cognition and cognitive effort is true by definition. The study uses data from 144 U.S. college students and employs moderated regression analysis followed by subgroup analysis to demonstrate plasticity. The results set a boundary condition to the generally presumed relationship between need for cognition and cognitive effort, thereby improving the understanding of how these phenomena are related. PMID- 22049655 TI - Lyrics of national anthems and suicide rates. AB - The suicide rates of 18 European nations were associated with the proportion of sad words in the lyrics of their national anthems as well as the gloominess of the music. It is suggested that a possible suicide prevention tactic might involve changing the music and lyrics of national anthems. PMID- 22049656 TI - Some psychometric properties of the Spanish version of the Clarity of Auditory Imagery Scale. AB - Few tests have been designed to measure auditory imagery. This study assessed the factor structure and internal consistency of the Spanish version of the Clarity of Auditory Imagery Scale (CAIS). Participants were 234 undergraduate students (M age = 19.6 yr.). Internal consistency reliability estimated by Cronbach's alpha was .82. In a principal components analysis followed by varimax orthogonal rotation, five factors were identified. Scores correlated moderately and positively with ratings on the Vividness of Visual Imagery Questionnaire-2 and negatively on the auditory scale of Betts' Questionnaire Upon Mental Imagery, but weakly and negatively with scores on the Measure of the Ability to Form Spatial Mental Imagery. PMID- 22049657 TI - Turkish validation of the Emotional Approach Coping Scale. AB - The Emotional Approach Coping Scale is frequently used to assess coping, which consists of emotional processing and emotional expression. The present aim was to examine the psychometric properties of this scale by utilizing two independent samples: university students (n = 481) and community members (n = 284). Based on goodness-of-fit indices in confirmatory factor analysis, a two-factor model yielded significant findings in these samples. The results of multi-group analysis revealed that the theoretical structure of the dispositional Emotional Approach Coping Scale was the same for men and women. In addition to sufficient internal consistency and test-retest reliability, the relationships between the Emotional Approach Coping Scale and five conceptually related measures (coping styles, positive affect, negative affect, depression, and trait anxiety) demonstrated concurrent validity. Furthermore, the present study provides a map of emotional approach coping styles in a non-Western culture. PMID- 22049658 TI - Higher rates of victimization to physical abuse by adults found among victims of school bullying. AB - Retrospective reports of exposure to physical abuse by an adult during childhood was assessed in 874 adolescents (426 boys, 448 girls; M age = 11.5 yr., SD = 0.8) who also reported whether they had been victimized by school bullying. Having been hit by an adult was significantly more common among victims of school bullying (39.5%) than among adolescents not victimized by school bullying (16.8%). No sex difference was found. The finding raises questions about whether victimization by physical abuse puts a child at greater risk for developing a "victim personality". PMID- 22049659 TI - Trust as a determinant of entrepreneurs' preference to remain tenants in Turkish business incubators. AB - Relations of two types of trust by entrepreneurs with the entrepreneurs' preference to remain an incubator tenant were examined using questionnaire data from 67 owners of companies in 6 Turkish incubators. As hypothesized, trust in incubator management had a positive and unique relation with preference to remain an incubator tenant. However, trust in other incubator tenants did not show the hypothesized positive and unique relation with preference to remain a tenant; the results indicated the relation is negative. PMID- 22049660 TI - Characteristics of the work environment related to older employees' willingness to continue working: intrinsic motivation as a mediator. AB - The relationships between older employees' willingness to continue working and characteristics of the work environment for older workers were investigated, as well as a possible mediation by intrinsic motivation. 103 employees ages 50 to 65 years, from various sectors of the Dutch labor market, completed questionnaires that measured willingness to continue working, intrinsic motivation, organizational stimulation, work variety, work challenge, and job autonomy. Hierarchical regression analyses showed organizational stimulation, as well as the various job characteristics, were positively related to employees' willingness to continue working. Moreover, intrinsic motivation fully mediated the relationship of work variety with willingness to continue working and partially mediated the relationships of organizational stimulation, work challenge, and job autonomy with willingness to continue working. It was concluded that organizations can encourage older workers to work until age 65 and beyond by shifting their focus from extrinsic to intrinsic rewards. PMID- 22049661 TI - Sorting food labels and describing properties of categories: stability of results between and within subjects. AB - The purpose of this research is to improve understanding of the consistency of the categorization process in cognitive psychology. To investigate the temporal stability of the categorization process between and within subjects, 100 participants (M = 22.1 yr., SD = 2.1) were required to sort 65 food labels into groups and to explain their grouping. The sorting and property generation of food labels were compared by conducting two sessions (with a 15-day interval) to assess within-subject variability. Two groups of participants were compared to assess between-subjects variability. The results from the sorting task showed excellent stability between and within subjects. Conversely, the property generation task showed high variability. It is concluded that the tasks involved different types of knowledge. The sorting task appeared to generate good agreement and to involve more stable knowledge. The task of producing properties may involve other mechanisms. This paper discusses the results in light of cognitive and pragmatic theories. PMID- 22049662 TI - The role of descriptive norm within the theory of planned behavior in predicting Korean Americans' exercise behavior. AB - There are few studies investigating psychosocial mechanisms in Korean Americans' exercise behavior. The present study tested the usefulness of the theory of planned behavior in predicting Korean American's exercise behavior and whether the descriptive norm (i.e., perceptions of what others do) improved the predictive validity of the theory of planned behavior. Using a retrospective design and self-report measures, web-survey responses from 198 Korean-American adults were analyzed using hierarchical regression analyses. The theory of planned behavior constructs accounted for 31% of exercise behavior and 43% of exercise intention. Intention and perceived behavioral control were significant predictors of exercise behavior. Although the descriptive norm did not augment the theory of planned behavior, all original constructs--attitude, injunctive norm (a narrow definition of subjective norm), and perceived behavioral control- statistically significantly predicted leisure-time physical activity intention. Future studies should consider random sampling, prospective design, and objective measures of physical activity. PMID- 22049663 TI - Intentional faking of the single category Implicit Association Test and the Implicit Association Test. AB - The Implicit Association Test (IAT) provides a relative measure of implicit association strengths between target and attribute categories. In contrast, the Single Category Implicit Association Test (SC-IAT) measures association strength with a single attribute category. This can be advantageous if a complementary category--as used in the IAT--cannot be composed or is undesired. If the SC-IAT is to be a meaningful supplement to the IAT, it should meet the same requirements. In an online experiment with a large and heterogeneous sample, the fakability of both implicit measures was investigated when measuring anxiety. Both measures were fakable through specific instruction (e.g., "Slow down your reactions") but unfakable through nonspecific faking instruction even though nonspecific instruction was given immediately before the critical blocks (e.g., "Alter your reaction times"). When comparing the methodological quality of both implicit measures, the SC-IAT had lower internal consistency than the IAT. Moreover, with specific faking instructions, the SC-IAT was possible to fake to a larger extent than the IAT. PMID- 22049664 TI - Reliability of informant ratings and spouse similarity based on the Temperament and Character Inventory. AB - A cohort of 136 Swedish spouse pairs rated themselves and each other with the Temperament and Character Inventory. The data allowed assessment of the reliability of ratings by knowledgeable informants compared to self-rating for this personality test. The reliability of the informant rating was in the expected range, with an average correlation of .58. Agreement was slightly higher for the Temperament dimensions than for the Character dimensions. Additionally, the design allowed evaluation of the similarity between husbands and wives across the seven dimensions measured by the TCI. Correlations between spouses in self reports were very low for Temperament, with only Harm Avoidance having a statistically significant correlation (.22, p < .05). On the other hand, all three Character dimensions were significantly correlated. These results support the conceptualization of Temperament and Character as separate components of personality. The results are consistent with previous reports on the personality of spouse pairs. PMID- 22049665 TI - Role ambiguity as a moderator of occupational self-efficacy and job satisfaction. AB - Role ambiguity was examined as a moderator of occupational self-efficacy and job satisfaction on the basis of the data obtained from 280 employees of U.S. housing finance agencies in four states. The interaction effect was found to be small but significant. The practical implications of role ambiguity at different levels of occupational self-efficacy were discussed. The value of reducing role ambiguity is higher for those who have low self-efficacy. The theoretical implications of the findings support the inclusion of dispositional and situational interactions in research regarding job satisfaction. PMID- 22049666 TI - Using generalizability theory to estimate the relative effect of class size and number of items on the dependability of student ratings of instruction. AB - Previous research on the effect of class size on student ratings of instruction has primarily investigated the effect of class size on the favorableness of these ratings rather than its effect on their reliability (dependability). A few studies have used "generalizability theory" to demonstrate the relative effect of class size on the dependability of student ratings of instruction. The purpose of the present study was to test the validity of the findings of these studies in a different cultural setting using a different student ratings questionnaire. Using a random-effect analysis of variance to estimate the variance components for a design in which students were nested within classes and crossed with items, it was found that the variance component for class size was appreciably larger than that for items. At least 20 students were needed to obtain a generalizability coefficient for relative decisions of .70 or more. Increasing the number of students has a greater effect on generalizability coefficients than increasing the number of items. PMID- 22049667 TI - Relationship between learning environment characteristics and academic engagement. AB - The relationship between learning environment characteristics and academic engagement of 777 Grade 6 children located in 41 learning environments was explored. Questionnaires were used to tap learning environment perceptions of children, their academic engagement, and their ethnic-cultural background. The basis of the learning environment questionnaire was the International System for Teacher Observation and Feedback (ISTOF). Factor analysis indicated three factors: the teacher as a helpful and good instructor (having good instructional skills, clear instruction), the teacher as promoter of active learning and differentiation, and the teacher as manager and organizer of classroom activities. Multilevel analysis indicated that about 12% of the differences in engagement between children was related to the learning environment. All the mentioned learning environment characteristics mattered, but the teacher as a helpful, good instructor was most important followed by the teacher as promoter of active learning and differentiation. PMID- 22049668 TI - A relative age effect in men's but not women's professional baseball: 1943-1954. AB - Birthdates of professional female and male baseball players active from 1943 to 1954 (the beginning and final years for professional female leagues) were matched for year of birth and league years and then compared by birth quarters, with a cutoff date beginning August 1. A relative age effect was noted for males, as there was a significantly different distribution of players across birth quarter, but there was no such effect for female professionals. Since players were matched for birth year and league play, the difference was unlikely to be due to seasonality differences in birth. Instead, the absence of a "relative age" effect for female players can be attributed to the absence of organized adolescent baseball for girls prior to the establishment of professional baseball leagues for women. PMID- 22049669 TI - Academic decision making and prospect theory. AB - Two studies are reported that investigate the applicability of prospect theory to college students' academic decision making. Exp. 1 failed to provide support for the risk-seeking portion of the fourfold pattern predicted by prospect theory but did find the greater weighting of losses over gains. Using a more sensitive dependent measure, in Exp. 2 the results of the first experiment were replicated in terms of the gain-loss effect and also found some support for the fourfold pattern in the interaction between probabilities and gain versus loss. The greatest risk-seeking was found in the high probability loss condition. PMID- 22049670 TI - Juveniles tried as adults: the age of the juvenile matters. AB - Serious juvenile crimes require evaluation of a child as a criminal defendant in adult court. In such cases, it is crucial to understand jurors' attitudes, biases, and ability to follow legal instructions and maintain fairness. 308 undergraduate psychology students served as mock jurors, were randomly separated into four groups, and each group read the same realistic summary of a trial with the defendant's age presented as 13, 15, 17, or 21 years. Participants were asked to render guilty or not guilty verdicts and, if guilty, to suggest sentences. Chi squared analysis indicated 13- and 15-year-old defendants were convicted less often than 17- and 21-year-old defendants, showing that jurors distinguished between juvenile defendants of different ages, but not minors and adults as defined by law. Additional analysis showed that age did not affect sentencing recommendations. Decision processes jurors use for juveniles tried as adults are discussed. PMID- 22049671 TI - Familiarity and environmental representations of a city: a self-report study. AB - "Sense of direction" is usually assessed by self-report. Several internal factors contribute to proficiency in navigation: spatial cognitive style, respondent's sex, and familiarity with the environment; however, questionnaires assessing sense of direction do not include all these factors. In a recent study, Nori and Piccardi reported that environmental familiarity was crucial for topographical orientation. Regardless of a person's spatial cognitive style (i.e., landmark, route, or survey), the greater their familiarity with the environment, the better their performance. In this study, a questionnaire was used, the Familiarity and Spatial Cognitive Style Scale, to measure 208 women's sense of direction and knowledge of their city of residence. Analysis showed that Spatial Cognitive Style predicted sense of direction but not town knowledge. By contrast, familiarity played a crucial role in both areas, confirming the importance of having a tool to assess this factor. PMID- 22049672 TI - Psychometrics of Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) scores. AB - A sample of 183 medical students completed the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT V2.0). Scores on the test were examined for evidence of reliability and factorial validity. Although Cronbach's alpha for the total scores was adequate (.79), many of the scales had low internal consistency (scale alphas ranged from .34 to .77; median = .48). Previous factor analyses of the MSCEIT are critiqued and the rationale for the current analysis is presented. Both confirmatory and exploratory factor analyses of the MSCEIT item parcels are reported. Pictures and faces items formed separate factors rather than loading on a Perception factor. Emotional Management appeared as a factor, but items from Blends and Facilitation failed to load consistently on any factor, rendering factors for Emotional Understanding and Emotional Facilitation problematic. PMID- 22049673 TI - The Coronary Health Improvement Project (CHIP) for lowering weight and improving psychosocial health. AB - This study extends previous research evaluating the association between the CHIP intervention, change in body weight, and change in psychological health. A randomized controlled health intervention study lasting 4 wk. was used with 348 participants from metropolitan Rockford, Illinois; ages ranged from 24 to 81 yr. Participants were assessed at baseline, 6 wk., and 6 mo. The Beck Depression Inventory (BDI) and three selected psychosocial measures from the SF-36 Health Survey were used. Significantly greater decreases in Body Mass Index (BMI) occurred after 6 wk. and 6 mo. follow-up for the intervention group compared with the control group, with greater decreases for participants in the overweight and obese categories. Significantly greater improvements were observed in BDI scores, role-emotional and social functioning, and mental health throughout follow-up for the intervention group. The greater the decrease in BMI through 6 wk., the better the chance of improved BDI score, role-emotional score, social functioning score, and mental health score, with odds ratios of 1.3 to 1.9. Similar results occurred through 6 mo., except the mental health variable became nonsignificant. These results indicate that the CHIP intervention significantly improved psychological health for at least six months afterwards, in part through its influence on lowering BMI. PMID- 22049674 TI - Boiler burden reduced at Bedford site. AB - With the NHS aiming to reduce its 2007 carbon footprint by 10% by 2015, Chris Horsley, managing director of Babcock Wanson UK, a provider of industrial boilers and burners, thermal oxidisers, air treatment, water treatment, and associated services, looks at how one NHS Trust has approached the challenge, and considerably reduced its carbon emissions, by refurbishing its boiler house and moving from oil to gas-fired steam generation. PMID- 22049675 TI - Seizing opportunities for realising savings. AB - Conor Ellis, global account leader, Health; Ed Baldwin, partner, and Dr Rachel Dick, consultant, at international built asset consultancy, EC Harris, provide an updated assessment on the current NHS estate, and, in the wake of the publication of an earlier detailed paper on the subject in late 2010, examine the extent to which NHS Trusts have made progress over the past year against 10 key steps to "unlocking value" outlined in the previous document. This article is an adapted version of the co-authors' 2011 paper, NHS Service and Estate Efficiency Report: Seizing The Opportunity. PMID- 22049676 TI - Making the right noise with hospital design. AB - Susan Witterick, director of Acoustics and Air Quality at Capita Symonds, examines the important role of acoustics in healthcare facility design in the "Age of Austerity", warning that, despite being a key factor in creating an optimal hospital environment for patients, staff, and visitors, it is too often still viewed as "a poor cousin at the design team table". PMID- 22049677 TI - Savings in its sights for Somerset Trust. AB - Colin Russell, healthcare specialist at Schneider Electric (pictured), explains how the company has recently worked with Taunton and Somerset NHS Foundation Trust to implement a major energy-saving project at the Trust's Musgrove Park Hospital in Taunton. He argues that, at a time when all areas of the service are being asked to reduce costs, such partnerships can potentially save the institution millions of pounds and significantly reduce carbon emissions, while "revitalising" parts of the NHS estate, and ensuring continuity of vital hospital services for facilities managers. PMID- 22049678 TI - Low carbon approach for clinical building. AB - Health Estate Journal reports on independent building services specialist, NG Bailey's important role on Phase 2A of the ongoing major redevelopment of one of the UK, and indeed one of the world's, most iconic children's healthcare facilities, Great Ormond Street Hospital in London. PMID- 22049679 TI - [Progress in zinc finger nuclease engineering for targeted genome modification]. AB - Zinc finger nuclease (ZFN) is an artificially engineered hybrid protein that contains a zinc finger protein (ZFP) domain and a Fok I endonuclease cleavage domain. It has recently emerged as a powerful molecular tool for targeted genome modifications. ZFNs recognize and bind to specific DNA sequences to generate a double-strand break (DSB) by its nuclease activity. Based on this finding, various genetic methods, including gene targeting (gene disruption), gene addition, gene correction etc., are being designed to manipulate the genomes of different species at specific loci. One particular advantage of this new technique is its broad applications, which can be employed to generate desirable inheritable mutations both at the organismal level and at the cellular level. Here, we review the recent progress and prospects of ZFN technology. This article focused on the mechanism of how it works, currently available target assessment, ZFP library construction and screening methods, target modification strategies, as well as a collection of specie and genes that have been successfully modified by ZFN. This review will provide a useful reference for researchers who are interested in applying this new technique in their studies. PMID- 22049680 TI - [Wnt signaling pathway and the Evo-Devo of deuterostome axis]. AB - A series of signal transduction pathways have been found to regulate the polarity establishment and formation of animal primary body axis. Among them, Wnt signaling pathway is extremely conserved and several key components in the pathway have been identified in the demosponge lineage. This implies that it is one of the earliest pathways involved in the ancestral metazoan axis development and might play an important role in specification and development of posterior and ventral fate of animal axis. Recently, with the establishment of functional experiments in vitro, the body plan formation has been found to be affected, in varying degrees, by many genes in the Wnt signaling pathway, such as members of wnt gene family, maternal gene beta-catenin and some transcription factor encoding genes. In this review, we analyzed the evolutionary origin of the wnt gene family involved in development of metazoan body plans, and then made a brief review on the roles of canonical Wnt/beta-catenin signaling in the polarity establishment and formation of primary body axis in diverse deuterostomes including sea urchin, amphioxus, zebrafish, frog, and mouse. PMID- 22049681 TI - [Research progress in molecular mechanism of animal seasonal reproduction]. AB - Animal seasonal reproduction involves complicated neuroendocrine processes of the hypothalamo-pituitary-gonadal axis. It is dominantly regulated by photoperiod, a crucial environmental cue. Melatonin, as internal photoperiod signal, regulates seasonal reproduction of animals. In recent years, it has been found that Kiss1/GPR54 system, which may influence GnRH secretion evidently, is regulated by both melatonin and feedback action of gonadal steroid hormones. Consequently, Kiss1/GPR54 system may play a key role in seasonal reproduction. Additionally, there exists another potential retrograde control pathway of seasonal breeding, which involves TSH-DIO2/DIO3 system. TSH-DIO2/ DIO3 system affects synthesis and secretion of GnRH and is regulated by melatonin, as well as Kiss1/GPR54 system. In this article, melatonin signal, especially the research advances of Kissl/GPR54 system and TSH-DIO2/DIO3 system were reviewed. PMID- 22049682 TI - [Molecular biological study on hormones in Acipenseriformes]. AB - Sturgeons belong to the Acipenseriformes, which provide an ideal model for evolutionary studies due to their unique characters. At present, many species of Acipenseriformes are very rare and near extinct. It is urgent to protect these species. However, data on molecular mechanisms of their growth and reproduction regulation are still limited. Hormones are important factors involved in these processes. In this paper, we summarized recent research progresses in the hormones in sturgeon, which will provide valuable information for further studies on molecular mechanisms of growth, sexual development, and reproduction regulation in Acipenseriformes. PMID- 22049683 TI - [DNA methylation in Drosophila, a review of recent studies]. AB - DNA methylation is a key mechanism underlying epigenetic regulation. Fruit fly has been considered as a free DNA methylation organism until recently a few studies demonstrated that genomic methylated DNA is prevalent during the early embryonic development; but the overall methylation level in Drosophila is lower than in vertebrates and plants. The putative genomic DNA methylation systerm in Drosophila contains a methyltransferase termed dDNMT2 and a methyl-binding protein dMBD2/3. dDNMT2 shows significant homology to the mammalian methyltransferases DNMT2 family, and dMBD2/3 encodes a protein with distinct homology to mammalian methyl-binding proteins MBD2 and MBD3. Some studies also indicated that methylation pattern varies among different species of Drosophila. This article summarizes the recent progresses in studies of DNA methylation in Drosophila. PMID- 22049684 TI - [Screening of mutations in SOD1 gene and analysis of genotype-phenotype correlation in Chinese patients with amyotrophic lateral sclerosis]. AB - In this study, we screened for the Cu/Zn superoxide dismutase (SOD1) mutations in 8 probands who had been clinically diagnosed with familiar amyotrophic lateral sclerosis (FALS) using PCR and direct sequencing. Two known mutations were detected in the three probands. Two probands carried the same Cys111Tyr (c.332G > A) mutation in exon 4, and others carried Gly147Asp (c.440G > A) mutation in exon 5. These two mutations were first reported in the Chinese ALS patients. After reviewing all clinical data of these three pedigrees, we found that Cys111Tyr led to a relatively mild phenotype and Gly147Asp displayed a rapidly progression, which needs to be confirmed by further study in more ALS patients. In conclusion, this study extends the spectrum of SOD1 mutations in the Chinese FALS patients and facilitates to investigate characteristics and distribution of SOD1 mutations in the Chinese population. PMID- 22049685 TI - [Correlation analysis between meiotic recombination frequencies and age in human spermatocyte]. AB - Faithful meiotic recombination is essential for the segregation of homologous chromosomes and the formation of normal haploid gametes. Little is known about the mechanism of meiotic recombination in human germ cells. MLHl (a DNA mismatch repair protein) foci on synaptonemal complexes (SCs) at prophase I of meiosis can be used to examine recombination frequency. In 10 fertile men, the mean number of MLH1 foci per cell in all donors was 49.4 with a range from 33 to 63. There was significant variation in the recombination frequency found among 10 normal individuals: the mean frequencies of chromosomal recombination foci ranged from 47 to 52.7. The bivalents without recombination focus were rare, with a frequency of only 0.4%. Thus, achiasmate chromosomes appeared to be rare in human male meiosis. Spearman correlation analysis between age and the frequencies of recombination foci failed to get any significantly statistical correlation, suggesting that aging contributes nothing to the variation among individuals. PMID- 22049686 TI - [The gene ontology and electro localization of ovine skin derived EST-SSR markers]. AB - Abstract: In order to study the potential gene function of ovine EST-SSR markers, nine original EST of Ovine Skin Derived polymorphic EST-SSR loci, which were developed in an early study by our lab, were ontology annotated and Electro localized. The results revealed that the original ESTs of the six loci had high homology with known genes and three of them probably played an important role in wool traits. Compared with its cDNA library, 8 loci were located on chromosomes of cattle. The homology of chromosomes between cattle and sheep was estimated based on the similarity coefficients calculated by positioning markers. Additionally, NJ clustering tree was establishedto serve for electro localization of ovine EST-SSR markers. Finally, 8 EST-SSR markers were successfully positioned on ovine chromosomes. The results from this study not only provide references for further studies on genetic mapping, in silico cloning of key genes for wool traits, but also are helpful to the researchs of chromosome evolution in animal. PMID- 22049687 TI - [Studies on SNP and genomic imprinting of the PEG1 gene in swine]. AB - PEG1 affects animal embryo growth and maternal behavior. The paternal allele specific expression of PEG1 was reported in most animal species, but the expressive pattern of PEG1 was not clear in piglets born. In order to investigate the imprinting pattern of PEG1 in pig, 166 samples were used to SNP of PEG1 from Landrace, Yorkshire, and Lantang breeds by PCR-SSCP. Single nucleotide polymorphism (SNP) of PEG1 in exon 12 was identfied. The genotype frequency and the expressive pattern were anslyzed in swine by RT-PCR-RFLP/SSCP. One SNP (a G- >A transition) was identified in exon 12 of PEG1. Maternal expression of PEG1 exon 12 was observed in all major organs (stomach, thymus, pancreas, spleen, lung, muscle, liver, tongue, kidney, brain, bladder, and heart) and placenta of three heterozygous pigs. PEG1 was paternally expressed and maternally imprinted in swine. PMID- 22049688 TI - [Polymorphism in coding region of pig PRDX6 gene and its genetic effects analysis]. AB - PRDX6, a member of antioxidant protein superfamily, plays an important role in oxidative stress, catabolism of lipids and phospholipid lipisomes. Therefore, we used PRDX6 as an important candidate gene for meat quality according to its physiological and biochemical function. Partial coding sequence of porcine PRDX6 was isolated and two potenial SNPs, one at 417 bp (C/T) and the other at 423 bp (A/G), were found in the fourth exon by comparison of the obtained sequence from different pig breeds. In order to explore the relationship between PRDX6 polymorphism and meat quality, genetic variation and trait association of these two SNPs were separately performed in 6 purebred pig population and 247 F2 "Large White x Meishan" resource population by pyrosequencing. The results showed that allele C was predominant in western pig breeds, while allele T was predominant in Chinese indigenous breeds at 417 bp (C/T). This SNP was significantly associated with the intramuscular fat and water moisture (P < 0.05). The A/G mutation at 423 bp was significantly associated with drip water rate, water holding capacity, intramuscular fat, and water moisture (P < 0.05). Allele A was predominant in western pig breeds, while allele G was predominant in Chinese indigenous breeds. These two SNPs were likely to be important markers affecting meat quality traits (especially the muscle tenderness). PMID- 22049689 TI - [TSA improve transgenic porcine cloned embryo development and transgene expression]. AB - Uncompleted epigenetic reprogramming is attributed to the low efficiency of producing transgenic cloned animals. Histone modification associated with epigenetics can directly influence the embryo development and transgene expression. Trichostatin A (TSA), as an inhibitor of histone deacetylase, can change the status of histone acetylation, improve somatic cell reprogramming, and enhance cloning efficiency. TSA prevents the chromatin structure from being condensed, so that transcription factor could binds to DNA sequence easily and enhance transgene expression. Our study established the optimal TSA treatment on porcine donor cells and cloned embryos, 250 nmol/L, 24 h and 40 nmol/L, 24 h, respectively. Furthermore, we found that both the cloned embryo and the donor cell treated by TSA resulted in the highest development efficiency. Meanwhile, TSA can improve transgene expression in donor cell and cloned embryo. In summary, TSA can significantly improve porcine reconstructed embryo development and transgene expression. PMID- 22049690 TI - [shRNAs driven by K14 promoter induce tissue-specific RNA interference]. AB - RNA interference is an efficient method for exploring gene function. Accumulating evidence suggests that RNA Pol II promoters can direct cell- or tissue-specific gene silencing. A eGFP-shRNA fusion construct transcribed from an RNA Pol II promoter (K14 promoter) was used to induce gene-specific shRNA silencing ofBMP4 gene expression. Recombinant vectors (pEGFP-C1-shRNA, psiCHECK-BMP4, and pEGFP K14-shRNA) were constructed. Vectors pEGFP-C1-shRNA and psiCHECK-BMP4 were cotransfected into Hela cells (in vitro) and shRNA-induced inhibition efficiency was tested by a luciferase assay. The results showed that all the six interference sequences inhibited the expression of BMP4 with high efficiency (>60%), and the interference sequence 5# showed the highest efficiency. For in vivo screening of JB6-C41 cells transfected with vector pEGFP-K14-shRNA, the inhibition efficiency was assayed by quantitative RT-PCR and Western blotting analyses. The results showed that the mRNA and protein products of the exogenous BMP4 gene were efficiently and specifically inhibited. The efficiency of gene silencing was greater than 60%, except for sequence 3#. The declines in mRNA and protein expression levels were significantly correlated during gene silence by the shRNA. This system may be adapted for in vivo shRNA expression and gene silencing. This method may provide a novel approach for the application of RNAi technology in suppressing gene expression in the analysis of the mechanisms of hair follicle development in sheep. PMID- 22049691 TI - [Whole cDNA sequence cloning and expression of chicken L-FABP gene and its relationship with lipid deposition of hybrid chickens]. AB - Liver fatty acid-binding protein (L-FABP) is closely related to intracellular transportation and deposition of lipids. A positive differential displayed fragment was found in the liver tissue among Silkie (CC), CAU-brown chicken (CD), and their reciprocal hybrids (CD and DC) at 8 weeks-old using differential display RT-PCR techniques (DDRT-PCR). Through recycling, sequencing, and alignment analysis, the fragment was identified as chicken liver fatty acid binding protein gene (L-FABP, GenBank accession number AY321365). Reverse Northern dot blot and semi-quantitative RT-PCR revealed that the avian L-FABP gene was over-expressed in the liver tissue of the reciprocal hybrids (CD and DC) compared to their parental lines (CC and DD), which was consistent with the fact that higher abdomen fat weight and wider inter-muscular fat width observed in the reciprocal hybrids. Considering the higher expression of L-FABP may contribute to the increased lipid deposition in the hybrid chickens, the functional study of avian L-FABP is warranted in future. PMID- 22049692 TI - [Genetic potential analysis of six tilapia populations by microsatellite DNA markers]. AB - Twenty five microsatellite loci were used to analyze two blue tilapia populations ["Xia'ao 1" (ZA), Guangxi population] and four nile tilapia populations [Egypt strain (ZN), 88 strain (XN), Guangxi population (GN), American strain (MN)]. A total of 7775 fragments ranging from 100 bp to 400 bp in length were obtained. Three to eight alleles were amplified in 25 loci and 143 alleles in all the six populations. The average number of alleles in each locus was 5.72. The average values of observed heterozygosity (Ho) ranged from 0.7253 to 0.8160, the average expected heterozygosity (He) ranged from 0.5146 to 0.6834, the average polymorphic information content (PIC) ranged from 0.4212 to 0.6105, and the number of average effective alleles (Ae) ranged from 2.20 to 3.23. The highest genetic similarity index was 0.9130 (between ZA and GA); and the lowest was 0.4352 (between ZA and ZN). The results showed that the four nile tilapia populations contained a high level of genetic potential, and the two blue tilapia populations were moderate. PMID- 22049693 TI - [Bioinformatic prediction of conserved microRNAs and their target genes in eggplant (Solanum melongena L.)]. AB - MicroRNAs (miRNAs), a recently discovered class of small (-21nt), non-coding, endogenous, single-stranded RNAs in eukaryotes, regulate gene expression negatively at the post-transcriptional levels depending on the extent of complementation between miRNA and mRNA. To date, a large number of miRNAs have been reported in many species, but none for eggplant (Solanum melongena L.). In this paper, a computational homology search approach based on the conservation of miRNA sequences and the stem-loop hairpin secondary structures of miRNAs was adopted. The search was started with the known plant miRNAs compared to eggplant expressed sequence tags (EST) databases to find potential miRNAs. Following a range of filtering criteria, a total of 16 potential miRNAs belonging to 12 families were identified. Three pairs of sense and antisense strand eggplant miRNAs belonging to three different miRNA families were also found. Furthermore, miR390 and miR399 sense/antisense pairs are identified for the first time in plants. Using online software psRNATarget, we further predicted the target genes of these 16 miRNAs and got 71 potential targets genes on base of 15 eggplant miRNAs. Most of these target genes were predicted to encode proteins that play key role in eggplant growth, development, metabolism, and stress responses. PMID- 22049694 TI - [Genome-wide analysis of the secreted proteins of phytophthora infestans]. AB - Based on the Phytophthora infestans genome sequence, we used bioinformatics and computer-based prediction algorithms to predict the secreted proteins of P infestans in detail, which would help us to elucidate the molecular mechanism underlying the interaction between the host plants and the P infestans. In this study, the signal peptide prediction algorithms SignalP v3.0 and PSORT, transmembrane helix prediction algorithms TMHMM-2.0 and THUMBUP, GPI-anchoring site prediction algorithm big-PI Predictor, and subcellular protein location distribution algorithm TargetP v1.01 were used to analyze the 22658 protein sequences of P infestans published. Our results suggested that there might be 671 secreted pro- teins, accounting for 3.0% of the total proteins. Among them, the functions of the 45 secreted proteins had been described previously. Their functions involved cellular metabolism and signal transduction etc. In addition, some of the secreted proteins were functionally similar to elicitin, which were likely to be associated with the virulence of P. infestans. PMID- 22049695 TI - [Research on the features of DNA methylation in leaves of different chronological ages of Phyllostachys heterocycla var. pubescens based on the method of MSAP]. AB - In order to probe the features of DNA methylation for bamboo stand with different chronological ages, the technique of methylation-sensitive amplified polymorphism (MSAP) was employed to detect DNA methylation in the paper. Experiment material is Moso bamboo (Phyllostachys heterocycla var. pubescens) leaves with 3 various chronological ages (5, 31, and > 60 years after seed germination). During the procedure of genome DNA extration and MSAP analysis, total 35 pairs of MSAP primers were amplyfied. The results showed that MSAP value for bamboo with those three chronological ages were respectively 24.44%, 28.21% and 32.12%, and full methylation ratios were 16.57%, 19.41% and 21.23%. Meanwhile, the value of variable sites for methylation reached 52.3% and for demethylation was 10.3%. Therefore, it could be concluded that with ages increasing MSAP value rising for Moso bamboo. Moreover the result of variance analysis for methylation ratio indicated that no significant (P = 0.307 > 0.05) difference among individuals with the same ages, while significant (P < 0.001) difference exsited among different chronological ages. Throuygh ANOVA it showed that 6 pairs (E3/HM2, E3/HM6, E3/HM7, E4/HM5, E4/HM6 and E5/HM5) of primers had obvious influence on DNA methylation for ones with different chronological ages and could be used for further research. PMID- 22049696 TI - [Investigation on the integrative course of genetics and genomics]. AB - Genomics is an important subdiscipline of genetics, and it forms a complete research system based on novel theories and techniques. Incorporating genomics in undergraduate curriculum is a response to the need of the development of genetics. The teaching of genomics has significant advantages on developing scientific thinking, enhances bioethics accomplishment, and professional interests in undergraduate students. The integration of genomics into genetics is in accordance with the principles of subject development and education. Related textbooks for undergraduate education are currently available in China, and it is feasible to set up a genetics and genomics integrative course by modifying teaching contents of the genetics course, selecting appropriate teaching approaches, and optimal application of the computer-assisted instruction. PMID- 22049697 TI - Gamma radiolysis of ceftriaxone sodium for water treatment: assessments of the activity. AB - As large quantities of antibiotics have been misused in human and veterinary medicine, many different classes of antibiotics with low concentration have been detected in the environmental water. This existence may cause severe ecosystem alterations. Ceftriaxone sodium was employed as the targeted antibiotic to evaluate gamma radiolysis of antibiotics based on the primary elimination test and activity assay. The decomposition percentage of ceftriaxone sodium (20 microg/ml) in purified water increases with increasing doses and reaches 98% under 5 kGy of gamma radiation. The residual activity after gamma radiation does not follow the corresponding decomposition percentage of ceftriaxone sodium. Liquid chromatography and mass spectrometry (LC-MS) was subsequently employed to analyze possible structures of radiolytic products relating to the activity. Different degrees of the residual activity may attribute to different cleavage pathways of ceftriaxone sodium produced by radiation with different doses. The results indicate that the radiolytic treatment is a highly-effective means for degradation of ceftriaxone sodium, and the activity status of ceftriaxone sodium after primary elimination should be taken into consideration for selecting a degrading dose. Three kGy is the appropriate dose for radiolysis of ceftriaxone sodium in purified water. PMID- 22049698 TI - Biosorption of Methylene Blue onto spent corncob substrate: kinetics, equilibrium and thermodynamic studies. AB - This study focuses on the possible use of the spent corncob substrate (SCS), an agricultural waste used after the cultivation of white rot fungus Pleurotus ostreatus, to adsorb Methylene Blue (MB) from aqueous solutions. A batch adsorption study was carried out with variable solution pH, adsorption time, temperature and initial MB concentration. It was found that MB uptake was favorable at pH ranging from 4.0 to 12.0 and the equilibrium adsorption capacity can be reached promptly within about 180 min. The biosorption data were also calculated by the pseudo-second-order kinetic model and Langmuir isotherm model. Thermodynamic parameters show that the adsorption is a spontaneous and endothermic process. The study highlighted a new pathway to develop potential low cost biosorbent for the removal of dye pollutants from wastewater. PMID- 22049699 TI - Removal of hexavalent chromium in soil and groundwater by supported nano zero valent iron on silica fume. AB - Silica fume supported-Fe(0) nanoparticles (SF-Fe(0)) were prepared using commercial silica fume as a support. The feasibility of using this SF-Fe(0) for reductive immobilization of Cr(VI) was investigated through batch tests. Compared with unsupported Fe(0), SF-Fe(0) was significantly more active in Cr(VI) removal especially in 84 wt% silica fume loading. Silica fume had also been found to inhibit the formation of Fe(III)/Cr(III) precipitation on Fe nanoparticles' surface, which was increasing the deactivation resistance of iron. Cr(VI) was removed through physical adsorption of Cr(VI) onto the SF-Fe(0) surface and subsequent reduction of Cr(VI) to Cr(III). The rate of reduction of Cr(VI) could be expressed by pseudo first-order reaction kinetics. The rate constant increased with the increase in iron loading but decreased with the increase in initial Cr(VI) concentration. Furthermore, column tests showed that the SF-Fe(0) could be readily transported in model soil. PMID- 22049700 TI - Lab scale study on electrocoagulation defluoridation process optimization along with aluminium leaching in the process and comparison with full scale plant operation. AB - An excess or lack of fluoride in drinking water is harmful to human health. Desirable and permissible standards of fluoride in drinking water are 1.0 and 1.5 mg/L, respectively, as per Indian drinking water quality standards i.e., BIS 10500, 1991. In this paper, the performance of an electro-coagulation defluoridation batch process with aluminium electrodes was investigated. Different operational conditions such as fluoride concentration in water, pH and current density were varied and performance of the process was examined. Influence of operational conditions on (i) electrode polarization phenomena, (ii) pH evolution during electrolysis and (iii) the amount of aluminium released (coagulant) was investigated. Removal by electrodes is primarily responsible for the high defluoridation efficiency and the adsorption by hydroxide aluminium floc provides secondary effect. Experimental data obtained at optimum conditions that favored simultaneous mixing and flotation confirmed that concentrations lower than 1 mg/L could be achieved when initial concentrations were between 2 and 20 mg/L. pH value was found to be an important parameter that affected fluoride removal significantly. The optimal initial pH range is between 6 and 7 at which effective defluoridation and removal efficiencies over 98% were achieved. Furthermore, experimental results prominently displayed that an increase in current density substantially reduces the treatment duration, but with increased residual aluminium level. The paper focuses on pilot scale defluoridation process optimization along with aluminium leaching and experimental results were compared with a full-scale plant having capacity of 600 liter per batch. PMID- 22049701 TI - Operational data of the Star City rainwater harvesting system and its role as a climate change adaptation and a social influence. AB - The Star City rainwater harvesting system (RWHS) was featured in the December, 2008, issue of Water 21. The article highlighted that the RWHS has a 3,000 m3 rainwater tank used in water saving, flood mitigation, and emergency response. Since then, many news media, public officials, and people from both South Korea and abroad have visited the RWHS. In this paper, two years of the system's operational data are presented and its role in short- and long-term climate change adaptation is investigated. The downstream sewer system has become safe for a 50-year rainfall without upgrading the existing sewer system, which was designed for a 10-year period. The 26,000 m3 of water saved has reduced the energy requirement of transferring water from a distant area. The success of the Star City RWHS has influenced 47 cities across South Korea, including Seoul, to enact regulations on rainwater management. It has shown that decentralized rainwater management can supplement the existing centralized system to ensure its safety. PMID- 22049702 TI - Low temperature biological phosphorus removal and partial nitrification in a pilot sequencing batch reactor system. AB - Partial nitrification and biological phosphorus removal appear to hold promise of a cost-effective and sustainable biological nutrient removal process. Pilot sequencing batch reactors (SBRs) were operated under anaerobic/aerobic configuration for 8 months. It was found that biological phosphorus removal can be achieved in an SBR system, along with the partial nitrification process. Sufficient volatile fatty acids supply was the key for enhanced biological phosphorus removal. This experiment demonstrated that partial nitrification can be achieved even at low temperature with high dissolved oxygen (>3 mg/L) concentration. Shorter solid retention time (SRT) for nitrite oxidizing bacteria (NOB) than for ammonia oxidizing bacteria due to the nitrite substrate limitation at the beginning of the aeration cycle was the reason that caused NOB wash-out. Controlling SRT should be the strategy for an SBR operated in cold climate to achieve partial nitrification. It was also found that the aerobic phosphorus accumulating organisms' P-uptake was more sensitive to nitrite inhibition than the process of anaerobic P-release. PMID- 22049703 TI - Inorganic greywater matrix impact on photocatalytic oxidation: does flocculation of TiO2 nanoparticles impair process efficiency? AB - This study was conducted in order to clarify whether photocatalyst flocculation- as observed in biologically pretreated greywater--contributes to photocatalytic oxidation (PCO) efficiency impairment. Aqueous solutions of tetraethyleneglycol dimethylether spiked with different inorganic salts in concentrations as found in biologically treated greywater were investigated with respect to TiO2 flocculation and PCO mineralisation kinetics. Flocculation of the photocatalyst primarily depended on pH (which was affected by the salts) and how close pH was to the point of zero charge (PZC). Photocatalyst agglomeration was maximum at pH 5.5. With salt concentrations >7 mmol L(-1), flocculation was strong even at pH far above PZC due to electric double layer compression. PCO rate constants were not unequivocally related to flocculation. Increasing pH was observed as the clearest factor deteriorating PCO efficiency. This was interpreted to result from impaired adsorbability of negatively charged oxidation intermediates as well as from enhanced CO2 absorption with increasing pH and subsequent formation of HCO3( ) anions which are OH radical scavengers. PMID- 22049704 TI - Degradation of methyl tert-butyl ether (MTBE) in water by glow discharge plasma. AB - This study evaluated the ability of the glow discharge plasma (GDP) technique to degrade methyl tert-butyl ether (MTBE) in an aqueous solution. The results showed that a large amount of hydrogen peroxide and highly active *OH free radicals were produced during the treatment. Various experimental parameters including discharge current, initial MTBE concentration and initial pH played significant roles on MTBE degradation. In addition, Fe2+ had a catalytic effect on the degradation of MTBE, which is potentially attributable to the reaction between Fe3+ and the hydrated electron. It was also confirmed that GDP was comparable to electrocatalytic oxidation and high-density plasma and more efficient than photocatalytic degradation techniques. These results suggest that GDP may become a competitive MTBE wastewater treatment technology. PMID- 22049705 TI - Pervaporative removal of acrylonitrile from aqueous streams through polydimethylsiloxane membrane. AB - This study describes the successful separation of acrylonitrile (ACN) from dilute aqueous streams using pervaporation process. The influences of ACN feed concentration, permeate pressure, operating temperature, feed flow rate and membrane thickness on the membrane separation performance were investigated. The results showed that with an increase in ACN concentration in the feed solution, the permeation flux of ACN increased while the enrichment factor decreased. It was also indicated that increasing the permeate pressure reduced the driving force for mass transfer and consequently the permeation flux dropped while the enrichment factor enhanced. Polydimethylsiloxane membranes used in this study showed very good properties in the separation process, leading to enrichment factors in the range of 70-140. Furthermore, the activation energy for pervaporation of both ACN and water calculated from Arrhenius plot indicated that the permeation of water through the membrane was more temperature dependant than ACN. PMID- 22049706 TI - Synthesis and structure-activity study of quaternary ammonium functionalized beta cyclodextrin-carboxymethylcellulose polymers. AB - Carboxymethylcellulose (CMC) and beta-cyclodextrin (beta-CD)-based polymers functionalized with two types of quaternary ammonium compounds (QACs), the alkaquat DMB-451 (N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride) (DMD-451) named polymer DMB-451, and FMB 1210-8 (a blend of 32 w% N alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride and 48 w% of didecyldimethylammonium chloride) named polymer FMB 1210-8, were synthethized and characterized by Fourier transform infrared spectroscopy. The antimicrobial activities of these polymers against Eschericia coli were also evaluated at 25 degrees C in wastewater. The results have indicated that the polymer FMB 1210-8 possesses a high-affinity binding with bacterial cells that induces a rapid disinfection process. Moreover, in the same experimental conditions of disinfection (mixture of 1.0 g of polymer and 100 mL of wastewater), the polymer FMB 1210-8 has a higher antimicrobial efficiency (99.90%) than polymer DMB-451 (92.8%). This phenomenon might be associated to a stronger interaction with bacterial cells due to stronger binding affinity for E. coli cells and greater killing efficiency of the C10 alkyl chains QAC of polymer FMB 1210-8 to disrupt the bacterial cell membrane as compared to N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride. Together, these results suggest that the polymer FMB 1210-8 could constitute a good disinfectant against Escherichia coli, which could be advantageously used in wastewater treatments due to the low toxicity of beta-CD and CMC, and moderated toxicity of FMB 1210-8 to human and environment. PMID- 22049707 TI - Research of waste dump water mutagenicity of bacterial detection system SOS chromotest. AB - The paper deals with a possible use of the bacterial detection system of SOS chromotest to test mutagenicity of waste dump water checking the mutagenicity degree on real samples from Praksice waste dump, which is a controlled waste dump with mixed industrial, municipal and inert wastes. The waste dump surface water samples were taken from a no-name influent stream springing below the waste dump body between 2005 and 2009. After metabolic activation by microsomal fraction in vitro, medium to high mutagenicity was registered in all the samples. The SOS chromotest is assessed as an effective and economically acceptable method to check and determine the mutagenicity degree of contaminated water. PMID- 22049708 TI - Dynamics of nitrogen oxides emission from a full-scale sludge liquor treatment plant with nitritation. AB - Biological treatment in wastewater treatment plants (WWTPs) is a source of nitrogen oxides (N2O, NO and NO2) emitted to the atmosphere. Aerobic ammonia oxidising bacteria (AOB) have been suggested to be the main source of these emissions. In a full-scale sludge liquor treatment plant at Sjolunda WWTP, it was shown that significant emissions of N2O, NO and NO2 do occur. The plant is operated with nitritation alone, which gives an environment enriched in aerobic AOB. During normal operation, emissions of N2O, NO and NO2 were found to be 3.8%, 0.06% and 0.01% of the ammonium nitrogen load. The N2O emissions were larger than the recommended estimated figure of the Intergovernmental Panel on Climate Change (IPCC) for a complete wastewater treatment plant. The N2O emissions correlated positively with the length of the previous anoxic period, i.e., settling and decantation, and with the ammonium oxidation rate. The NO and NO2 emission profiles were similar and dependent on ammonium oxidation and DO level, but the NO2 concentrations were always lower. PMID- 22049709 TI - Screening optimisation for indirect potable reuse. AB - An automatic backflush pre-filter used for pre-treatment for secondary wastewater re-use was evaluated and optimised at two different mesh sizes over an 18 month period. The filter was initially run with a 500 microm rating mesh size, as recommended by the supplier of the downstream membrane filtration process, and then at 100 microm to investigate any change in water quality produced and associated improved membrane performance. With the 500 microm mesh in place, the filter fouling rate was low and a backflush was initiated every 3.5 h. For the 100 microm mesh the fouling rate was extremely rapid. Fouling was found to be caused by reverse side blockage of the pre-filter due to biofilm growth, and not by improved solids capture; there was no improvement in water quality with the smaller mesh size, since particle unloading from the biofilm took place. The pre filter fouling rate was found to be related to turbidity. At a turbidity of 5 NTU the filter backflushed around 200 times per day, while at 10 NTU this increased to over 300 times. Further analysis enabled the backflush water volume to be decreased by reducing the backflush duration and increasing the backflush cycle time (i.e. the time between backflushes). PMID- 22049710 TI - Impact of Microcystis aeruginosa on membrane fouling in a biologically treated effluent. AB - Microcystis aeruginosa was cultured in biologically treated municipal effluent to simulate blue-green algal bloom conditions in a treatment lagoon. The effect of algae in the early, mid and late phases of growth on membrane fouling, chemical coagulation (alum or aluminium chlorohydrate (ACH)) and hydraulic cleaning on the microfiltration of this effluent was investigated. The effect of M. aeruginosa in the early phase was negligible and gave a similar flux profile and permeate volume to that of effluent alone. The increase in M. aeruginosa concentration for the mid and late phases caused a significant reduction in permeate volume compared with the early phase. Full flux recovery was achieved with an alum dose of 1 mg Al3+ L(-1) (early phase) and 10 mg Al3+ L(-1) (mid phase), demonstrating that membrane fouling was hydraulically reversible. For the late phase, the highest flux recovery was 89%, which was achieved with an alum dose of 5 mg Al3+ L(-1). Higher alum dosages resulted in a reduction in flux recovery. The use of 1.5 pm pre-filtration after alum treatment showed little improvement in water quality but led to a drastic reduction in flux recovery, which was attributed to diminishing the protective layer on the membrane surface, thus enabling internal fouling. The performance of ACH was comparable to alum at low dissolved organic carbon (DOC) and cell concentration, but was not as effective as alum at high DOC and cell concentration due to the formation of more compact ACH flocs, which resulted in a higher cake layer specific resistance, leading to the deterioration of performance. PMID- 22049711 TI - The dissolution characteristics of calcium sulfide and utilization as a precipitation agent in acidic wastewater effluent treatment. AB - The dissolution characteristics of CaS in the presence of CO2 has been investigated by monitoring sulfide speciation, solution conductivity and pH during dissolution. The sulfide speciation associated with CaS dissolution was utilized for metal precipitation from acidic wastewater effluents. The mechanism involved in the dissolution process was observed to be pH-dependent, characterized by increased solution conductivity as the HS(-) species becomes dominant in solution in the form of the Ca(HS)2 complex. The replacement of HS(-) by CO3(2-) in the Ca(HS)2 complex triggered CaCO3 precipitation and H2S stripping and this was characterized by decreased solution pH and conductivity. The sulfide to total metal molar ratio was observed to have an effect on the pH and therefore sulfide speciation as well as extent of metal removal. The utilization of CaS in the treatment of acidic wastewater effluents demonstrated complete metal removal, with the potential of a pH-controlled selective metal removal and recovery. PMID- 22049712 TI - Retrofitting a stormwater retention pond using a deflector island. AB - Stormwater retention ponds are one of the principal methods to treat stormwater runoff. Analysis of residence time distribution (RTD) curves can be used to evaluate the capability of these ponds for sediment removal. Deflector islands have been suggested as a means of improving the performance of retention ponds, due to their diffusing the inlet jet. In this study, the effect of an island on retention pond performance was investigated using a physical model of an existing stormwater retention pond. The physical model is a trapezoidal pond having top dimensions 4.1 x 1.5 x 0.23 m and side slopes of 2:1 (h:v). Three different arrangements were studied. The results show that placing an island to deflect the influent to a stormwater retention pond does not improve pond performance, rather it stimulates short-circuiting. This unexpected behaviour, in relation to previous studies, is considered to be a consequence of the model pond incorporating sloping walls; which is a novel aspect of this paper. PMID- 22049713 TI - Development of headspace-gas chromatography-flame ionization detection procedure to determine volatile fatty acids in zoo organic waste leachates. AB - In order to determine volatile fatty acids (short chain monocarboxylic acids with 2 to 6 carbon atoms in a molecule) in leachates formed in organic waste piles a procedure based on static headspace (HS) coupled with gas chromatography (GC) have been proposed and optimized. The conditions of HS extraction and sample introduction into a gas chromatograph as well as of chromatographic separation were considered. Using flame ionization detection LODs were of the order of 0.02 0.37 mg/L. The analyzed leachate collecting on and close to a zoo organic waste pile contained VFAs (Volatile Fatty Acids) at a concentration ranging from 5.5 mg/L to 0.88 g/L and from below LOD to 10.1 mg/L for pool water at some distance from the pile, respectively. PMID- 22049714 TI - The fate of 14C-radiolabelled diclofenac and 4'-hydroxydiclofenac in membrane bioreactor treatment of wastewater. AB - This study aimed at enhancing knowledge on the fate of diclofenac (DF), together with its main human metabolite 4'-hydroxydiclofenac (4'OHDF), during wastewater treatment by using a laboratory-scale membrane bioreactor (MBR). The reactor was fed continuously with non-radiolabelled diclofenac for a one month period prior to a single pulse of a 14C-radiolabelled solution of DF and 4'OHDF. The solution spike contained approximately 25% 4'OHDF and 65% DF, which corresponds to the ratio observed in municipal sewage, as well as traces of two other metabolites. The radioactivity was monitored for a total of twelve days in the various output streams. The calculation of the complete mass balance in the system demonstrated that the major part of the radioactivity left the reactor with the permeate (88.7%), while 2.1% was recovered in the excess sludge. Negligible amounts were recovered in the off-gas traps and on the membranes. Chromatographic analyses of effluent samples, by means of HPLC-MS coupled in parallel to a radiodetector, displayed a different pattern than the one of the spiked solution. It showed the occurrence of three additional metabolites. PMID- 22049715 TI - Evaluation of the pollution load discharged at an upstream industry--Egypt--and methods for its reduction. AB - Oil exploration in Egypt is a major contributor to the national Gross Domestic Product (GDP). With 50-65% of the oil resources located in the Gulf of Suez (GoS) region, the impact of such activity upon the region's water environment and its quality cannot be overlooked because of the volume of effluent generated. The objective of this study (September 2000-September 2001) was to assess the impact of a 650,000 barrels/day (bl/d) (100,000 m3/d) effluent arising from a major oil exploration site located south of GoS upon the local water environment. Another objective was to identify the pollutant contents amenable for reduction relative to the new Egyptian regulations. This was achieved by the characterization of the main contributing streams and the identification of the final effluent parameter constraints relative to the type of injection waters used. Subsequent investigations for the reduction of these contents were conducted on site and the results obtained are reviewed herewith. PMID- 22049716 TI - Electro-thermal treatment optimization of high concentration ammonia nitrogen by gaseous oxidation in liquid phase (GOLP). AB - This study is focused on optimizing the treatment parameters for high concentration ammonia using gaseous oxidation in liquid phase (GOLP). The conversion of ammonia was achieved electrothermally over mono-crystalline silicon supported CoOx catalyst. The experimental results demonstrated that factors including the co-anions, pH of the solutions, air flowrate and the current showed apparent influences on the ammonia removal. The higher the Cl(-) concentration and/or current, the better the efficiency of ammonia degradation. The increase of the air flowrate would increase the ammonia removal accordingly. And it was also observed that the pH declined during the ammonia conversion, and the neutral and alkaline pH were beneficial to the ammonia removal. The preliminary cost analysis based on lab data was also provided for future reference. PMID- 22049717 TI - Fouling cake layer in a submerged anaerobic membrane bioreactor treating saline wastewaters: curse or a blessing? AB - The treatment of inhibitory (saline) wastewaters is known to produce considerable amounts of soluble microbial products (SMPs), and this has been implicated in membrane fouling; the fate of these SMPs was of considerable interest in this work. This study also investigated the contribution of SMPs to membrane fouling of the; (a) cake layer/biofilm layer, (b) the compounds below the biofilm/cake layer and strongly attached to the surface of the membrane, (c) the compounds in the inner pores of the membrane, and (d) the membrane. It was found that the cake/biofilm layer was the main reason for fouling of the membrane. Interestingly, the bacteria attached to the cake/biofilm layer showed higher biodegradation rates compared with the bacteria in suspension. Moreover, the bacteria attached to the cake layer showed higher amounts of attached extracellular polysaccharides (EPS) compared with the bacteria in suspension, possibly due to accumulation of the released EPS from suspended biomass in the cake/biofilm layer. Molecular weight (MW) analysis of the effluent and reactor bulk showed that the cake layer can retain a large fraction of the SMPs in the reactor and prevent them from being released into the effluent. Hence, while cake layers lead to lower fluxes in submerged anaerobic membrane bioreactors (SAMBRS), and hence higher costs, they can improve the quality of the reactor effluent. PMID- 22049718 TI - Opportunities for public water utilities in the market of energy from water. AB - An inventory is made of the possibilities to recover sustainable energy from the water cycle by identifying different water flows in a municipal environment as a sustainable energy source. It is discussed what role public water utilities should play in the market of energy from water. This is done for Waternet, the public water utility of Amsterdam, by describing experiences on two practical applications for aquifer thermal energy storage and energy recovery from drinking water. The main conclusion is that public water utilities can substantially contribute to the production of sustainable energy, especially by making use of heat and cold from the water cycle. Public water utilities have the opportunity to both regulate and enter the market for energy from water. PMID- 22049719 TI - Blending anaerobic co-digestates: synergism and economics. AB - Co-digestion is the process in which wastes from various sources are treated together. Therefore, more organic carbon is added to make efficient use of existing digesters. The objectives of this study were to compare potential co digestates, determine synergistic and antagonistic co-digestion outcomes and estimate economic benefits for preliminary screening. Over 80 wastes were identified from 54 facilities within 160 km of an existing municipal digester. Synergistic, antagonistic and neutral co-digestion outcomes were observed for the various wastes. A simple economic comparison resulted in the greatest potential benefits for four co-digestates: yeast flavorings production waste, meat production dissolved air flotation float, acid whey from cheese production and thin stillage from corn ethanol production. Performance was investigated using bench-scale digesters receiving primary sludge with and without co-digestates. Methane production rates were 105 and 66% higher when co-digestates were present, but were anticipated to increase only 57 and 23% due to the additional chemical oxygen demand. Therefore, significant synergistic outcomes were observed during co-digestion. Co-digestion of the most promising wastes with primary sludge in full scale was estimated to generate enough electricity to power more than 2,500 houses. PMID- 22049720 TI - Effect of pH on nitrate and selenate reduction in flue gas desulfurization brine using the H2-based membrane biofilm reactor (MBfR). AB - Increased tightening of air regulations is leading more electric utilities to install flue gas desulfurization (FGD) systems. These systems produce brine containing high concentrations of nitrate, nitrite, and selenate which must be removed before discharge. The H2-based membrane biofilm reactor (MBfR) was shown to consistently remove nitrate, nitrite, and selenate at high efficiencies. The maximum selenate removal flux reached 362 mgSe m(-2)d(-1) and was higher than that observed in earlier research, which shows continual improvement of the biofilm for selenate reduction. A low pH of 6.8 inhibited precipitation when treating actual FGD brine, yet did not inhibit removal. SO4(2-) was not removed and therefore did not compete with nitrate, nitrite, and selenate reduction for the available H2. PMID- 22049721 TI - Integrated constructed wetlands: water management as a land-use issue, implementing the 'Ecosystem Approach'. AB - Awareness of the need for social, economic and environmental coherence in the management of water is becoming evermore apparent. Water supply as well as treatment is becoming more costly; a challenge that is not only limited to developing countries. The use of wetlands, natural and constructed, is now more widely accepted as a means of tackling a range of problems in water management to deliver this coherence. The use of 16 Integrated Constructed Wetlands that mimic shallow, emergent-vegetated, palustrine wetlands in a 2,500 ha catchment in County Waterford, Southeast Ireland, has shown a number of distinct advantages in implementing the all encompassing 'Ecosystem Approach', addressing the key elements for sustainable water management in an intensively used agricultural area. The significant increase in water quality, biodiversity, social amenities and acceptance by the local rural community provided by this 'real' field-scale demonstration show the benefits that such a joined-up approach can have on catchment management in the widest sense. PMID- 22049722 TI - Effect of polyaluminium chloride on phosphorus removal in constructed wetlands treated with swine wastewater. AB - Total phosphorus (TP) removal in aged constructed wetlands poses a challenge, especially when treated with swine wastewater with high concentrations of phosphorus (P). Our earlier studies with anaerobic lagoon swine wastewater treatment in constructed wetlands showed a decline in P removal (45-22%) with increased years of operation. These particular wetlands have been treated with swine wastewater every year since the first application in 1997. Preliminary lab scale studies were conducted to evaluate the efficiency of polyaluminium chloride (PAC) in the removal of phosphate-P (PO4-P) from swine wastewater. The experimental objective was to increase the phosphorus treatment efficiency in constructed wetland by adding PAC as a precipitating agent. PAC was added by continuous injection to each wetland system at a rate of 3 L day(-1) (1:5 dilution of concentrated PAC). Swine wastewater was added from an anaerobic lagoon to four constructed wetland cells (11m wide x 40m long) at TP loads of 5.4 6.1 kg ha(-1) day(-1) in two experimental periods, September to November of 2008 and 2009. Treatment efficiency of two wetland systems: marsh-pond-marsh (M-P-M) and continuous marsh (CM) was compared. The wetlands were planted with cattails (Typha latifolia L.) and bulrushes (Scirpus americanus). In 2008, PAC treatment showed an increase of 27.5 and 40.8% of TP removal over control in M-P-M and CM respectively. Similar trend was also observed in the following year. PAC as a flocculant and precipitating agent showed potential to enhance TP removal in constructed wetlands treated with swine wastewater. PMID- 22049723 TI - Application of PTFE membrane for ammonia removal in a membrane contactor. AB - The feasibility of a membrane contactor system for ammonia removal was studied. The mass transfer coefficient was used to quantitatively compare the effect of various operation conditions on ammonia removal efficiency. Effective removal of ammonia was possible with a Polytetrafluoroethylene (PTFE) membrane contactor system at all tested conditions. Among the various operation parameters, contact time and solution pH showed significant effect on the ammonia removal mechanism. The overall ammonia removal rate was not affected by influent suspended solution concentration unlike other pressure driven membrane filtration processes. Also the osmotic distillation phenomena which deteriorate the mass transfer efficiency can be minimized by preheating of influent wastewater. A membrane contactor system can be a possible alternative to treat high strength nitrogen wastewater by optimizing operation conditions such as stripping solution flow rate, influent wastewater temperature, and influent pH. PMID- 22049724 TI - Estimated costs of implementation of membrane processes for on-site greywater recycling. AB - Greywater reuse inside buildings is a possible way to preserve water resources and face up to water scarcity. This study is focused on a technical-economic analysis of greywater treatment by a direct nanofiltration (NF) process or by a submerged membrane bioreactor (SMBR) for on-site recycling. The aim of this paper is to analyse the cost of recycled water for two different configurations (50 and 500 inhabitants) in order to demonstrate the relevance of the implementation of membrane processes for greywater recycling, depending on the production capacity of the equipment and the price of drinking water. The first step was to define a method to access the description of the cost of producing recycled water. The direct costs were defined as a sum of fixed costs due to equipment, maintenance and depreciation, and variable costs generated by chemical products and electricity consumptions. They were estimated from an experimental approach and from data found in literature, enabling operating conditions for greywater recycling to be determined. The cost of treated water by a SMBR unit with a processing capacity of 500 persons is close to 4.40 euros m(-3), while the cost is 4.81 euros m(-3) with a NF process running in the same conditions. These costs are similar to the price of drinking water in some European countries. PMID- 22049725 TI - Development of a screening method to assess flood risk on danish national roads and highway systems. AB - A method to assess flood risk on Danish national roads in a large area in the middle and southern part of Jutland, Denmark, was developed for the Danish Road Directorate. Flood risk has gained renewed focus due to the climate changes in recent years and extreme rain events are expected to become more frequent in the future. The assessment was primarily based on a digital terrain model (DTM) covering 7,500 km2 in a 1.6 x 1.6 m grid. The high-resolution terrain model was chosen in order to get an accurate estimation of the potential flooding in the road area and in the immediate vicinity, but also put a high requirement on the methods, hardware and software applied. The outcome of the analysis was detailed maps (as GIS layers) illustrating the location of depressions with depths, surface area and volume data for each depression. Furthermore, preferential flow paths, catchment boundaries and ranking of each depression were calculated. The ranking was based on volume of depressions compared with upstream catchment and a sensitivity analysis of the runoff coefficient. Finally, a method for assessing flood risk at a more advanced level (hydrodynamic simulation of surface and drainage) was developed and used on a specific blue spot as an example. The case study shows that upstream catchment, depressions, drainage system, and use of hydrodynamic calculations have a great influence on the result. Upstream catchments can contribute greatly to the flooding. PMID- 22049726 TI - Quantification of increased flood risk due to global climate change for urban river management planning. AB - Global climate change is expected to affect future rainfall patterns. These changes should be taken into account when assessing future flooding risks. This study presents a method for quantifying the increase in flood risk caused by global climate change for use in urban flood risk management. Flood risk in this context is defined as the product of flood damage potential and the probability of its occurrence. The study uses a geographic information system-based flood damage prediction model to calculate the flood damage caused by design storms with different return periods. Estimation of the monetary damages these storms produce and their return periods are precursors to flood risk calculations. The design storms are developed from modified intensity-duration-frequency relationships generated by simulations of global climate change scenarios (e.g. CGCM2A2). The risk assessment method is applied to the Kanda River basin in Tokyo, Japan. The assessment provides insights not only into the flood risk cost increase due to global warming, and the impact that increase may have on flood control infrastructure planning. PMID- 22049727 TI - Samplinghelper a web-based tool to assess the reliability of sampling strategies in sewers and receiving waters. AB - Sampling is a key step in the analysis of chemical compounds. It is particularly important in the environmental field, for example for wastewater effluents, wet weather discharges or streams in which the flows and concentrations vary greatly over time. In contrast to the improvements that have occurred in analytical measurement, developments in the field of sampling are less active. However, sampling errors may exceed by an order of magnitude those related to analytical processes. We proposed an Internet-based application based on a sampling theory to identify and quantify the errors in the process of taking samples. This general theory of sampling, already applied to different areas, helps to answer questions related to the number of samples, their volume, their representativeness, etc. The use of the internet to host this application facilitates use of theoretical tools and raise awareness of the uncertainties related to sampling. An example is presented, which highlights the importance of the sampling step in the quality of analytical results. PMID- 22049728 TI - Assessing dry weather flow contribution in TSS and COD storm events loads in combined sewer systems. AB - Continuous high resolution long term turbidity measurements along with continuous discharge measurements are now recognised as an appropriate technique for the estimation of in sewer total suspended solids (TSS) and Chemical Oxygen Demand (COD) loads during storm events. In the combined system of the Ecully urban catchment (Lyon, France), this technique is implemented since 2003, with more than 200 storm events monitored. This paper presents a method for the estimation of the dry weather (DW) contribution to measured total TSS and COD event loads with special attention devoted to uncertainties assessment. The method accounts for the dynamics of both discharge and turbidity time series at two minutes time step. The study is based on 180 DW days monitored in 2007-2008. Three distinct classes of DW days were evidenced. Variability analysis and quantification showed that no seasonal effect and no trend over the year were detectable. The law of propagation of uncertainties is applicable for uncertainties estimation. The method has then been applied to all measured storm events. This study confirms the interest of long term continuous discharge and turbidity time series in sewer systems, especially in the perspective of wet weather quality modelling. PMID- 22049729 TI - Cementitious porous pavement in stormwater quality control: pH and alkalinity elevation. AB - A certain level of alkalinity acts as a buffer and maintains the pH value in a stable range in water bodies. With rapid urban development, more and more acidic pollutants flow to watersheds with runoff and drop alkalinity to a very low level and ultimately degrade the water environment. Cementitious porous pavement is an effective tool for stormwater acidic neutralization. When stormwater infiltrates cement porous pavement (CPP) materials, alkalinity and pH will be elevated due to the basic characteristics of cement concrete. The elevated alkalinity will neutralize acids in water bodies and maintain the pH in a stable level as a buffer. It is expected that CPP materials still have a certain capability of alkalinity elevation after years of service, which is important for CPP as an effective tool for stormwater management. However, few previous studies have reported on how CPP structures would elevate runoff alkalinity and pH after being exposed to rainfall-runoff for years. In this study, three groups of CPP specimens, all exposed to rainfall-runoff for 3 years, were used to test the pH and alkalinity elevation properties. It was found that runoff pH values were elevated from 7.4 to the range of 7.8-8.6 after infiltrating through the uncoated specimens, and from 7.4 to 8.5-10.7 after infiltrating through aluminum-coated specimens. Runoff alkalinity elevation efficiencies are 11.5-14.5% for uncoated specimens and 42.2% for coated specimens. The study shows that CPP is an effective passive unit operation for stormwater acid neutralization in our built environment. PMID- 22049730 TI - A performance evaluation of three membrane bioreactor systems: aerobic, anaerobic, and attached-growth. AB - Water sustainability is essential for meeting human needs for drinking water and sanitation in both developing and developed countries. Reuse, decentralization, and low energy consumption are key objectives to achieve sustainability in wastewater treatment. Consideration of these objectives has led to the development of new and tailored technologies in order to balance societal needs with the protection of natural systems. Membrane bioreactors (MBRs) are one such technology. In this investigation, a comparison of MBR performance is presented. Laboratory-scale submerged aerobic MBR (AMBR), anaerobic MBR (AnMBR), and attached-growth aerobic MBR (AtMBR) systems were evaluated for treating domestic wastewater under the same operating conditions. Long-term chemical oxygen demand (COD) and total organic carbon (TOC) monitoring showed greater than 80% removal in the three systems. The AnMBR system required three months of acclimation prior to steady operation, compared to one month for the aerobic systems. The AnMBR system exhibited a constant mixed liquor suspended solids concentration at an infinite solids retention time (i.e. no solids wasting), while the aerobic MBR systems produced approximately 0.25 g of biomass per gram of COD removed. This suggests a more economical solids management associated with the AnMBR system. Critical flux experiments were performed to evaluate fouling potential of the MBR systems. Results showed similar critical flux values between the AMBR and the AnMBR systems, while the AtMBR system showed relatively higher critical flux value. This result suggests a positive role of the attached-growth media in controlling membrane fouling in MBR systems. PMID- 22049731 TI - Constructed wetland as a low cost and sustainable solution for wastewater treatment adapted to rural settlements: the Chorfech wastewater treatment pilot plant. AB - The paper presents the detailed design and some preliminary results obtained from a study regarding a wastewater treatment pilot plant (WWTPP), serving as a multistage constructed wetland (CW) located at the rural settlement of 'Chorfech 24' (Tunisia). The WWTPP implemented at Chorfech 24 is mainly designed as a demonstration of sustainable water management solutions (low-cost wastewater treatment), in order to prove the efficiency of these solutions working under real Tunisian conditions and ultimately allow the further spreading of the demonstrated techniques. The pilot activity also aims to help gain experience with the implemented techniques and to improve them when necessary to be recommended for wide application in rural settlements in Tunisia and similar situations worldwide. The selected WWTPP at Chorfech 24 (rural settlement of 50 houses counting 350 inhabitants) consists of one Imhoff tank for pre-treatment, and three stages in series: as first stage a horizontal subsurface flow CW system, as second stage a subsurface vertical flow CW system, and a third horizontal flow CW. The sludge of the Imhoff tank is treated in a sludge composting bed. The performances of the different components as well as the whole treatment system were presented based on 3 months monitoring. The results shown in this paper are related to carbon, nitrogen and phosphorus removal as well as to reduction of micro-organisms. The mean overall removal rates of the Chorfech WWTPP during the monitored period have been, respectively, equal to 97% for total suspended solids and biochemical oxygen demand (BOD5), 95% for chemical oxygen demand, 71% for total nitrogen and 82% for P-PO4. The removal of E. coli by the whole system is 2.5 log units. PMID- 22049732 TI - Element patterns for particulate matter in stormwater effluent. AB - Particulate matter in stormwater deteriorates the quality of receiving water and sediment. Characterization of stormwater particulate matter by means of its particle-associated element pattern provides an aid to determining its impact on receiving surface waters. During a 6 month measurement campaign, we determined particle-associated concentrations of major pollutants and rare earths for three combined water/stormwater outlets in the town of Stassfurt. We differentiated the particle-associated constituents on the basis of a hierarchical cluster analysis. Repeating the cluster analysis on random subsets, we gained information about the variability of the element patterns between and within the sites. In general, constituents associated with sewage and sewer sediment behave differently compared with constituents associated with runoff. The degree to which associations can be established for element patterns from site to site is limited by the variability encountered within sample sets taken from individual sites. The latter variability depends on the complexity of the catchment. PMID- 22049733 TI - Multiphase modeling study for storm water solids treatment in experimental storm water settling chamber. AB - This study tests four different types of multiphase models to determine the most appropriate model for predicting the behaviors of various types of storm water solids in a settling chamber. The Lagrangian reference frame discrete phase models of uncoupled and coupled models based on the interaction between the discrete phase and the continuous phase were tested. The rigid moving objects model providing six degrees of freedom particle motion was also tested to model non-spherical particle motion. The fourth model was a sediment transport model using the Eulerian reference frame model. This study tested five different storm water solids consisting of bulk, gross, coarse, sediment and fine which are classified by particle size and settling characteristics. Particle settling efficiency and computational time were considered in determining the most appropriate multiphase model. The coupled model provided better solid settling than the uncoupled model, but required 8.2% more computational time in this study. The Eulerian model matched settling efficiency for the high density finer solids. Although the Eulerian model showed reliable settling prediction, the Lagrangian coupled model can be an effective alternative requiring significantly reduced computational time. PMID- 22049734 TI - Assessment of diffuser pressure loss on WWTPs in Baden-Wurttemberg. AB - Aeration of activated sludge is a critical treatment step for the operation of activated sludge plants. To achieve a cost effective treatment process, assessing and benchmarking of aeration system performance are important measures. A simple means of gauging the relative condition of a fine bubble diffused aeration system is to evaluate the pressure loss of the diffusers as oxygen transfer tests are rarely applied during the lifetime of an aeration system. This paper shows an assessment of fine bubble diffuser systems in Baden-Wurttemberg, Germany, based on the results of a questionnaire sent to 941 WWTPs. Apart from the results with regards to the diffuser pressure loss, this paper also presents information on the current state of diffuser technology such as types and materials as well as the diffuser cleaning methods used in Baden-Wurttemberg. The majority of the WWTPs were equipped with tube diffusers (71%) with 50% of all plants having EPDM membranes installed. Regular mechanical cleaning is the most common cleaning method followed by regular pressure release/air-bumping programs during operations. With regard to the diffuser pressure loss it was found that 50% of the evaluated plants had a diffuser pressure loss that was twice as high as measured for new diffusers. PMID- 22049735 TI - Oxygen transfer in activated sludge--new insights and potentials for cost saving. AB - The alpha-factor has the greatest impact on the calculation of the required standard oxygen transfer rate (SOTR) in activated sludge systems equipped with submerged aeration systems. Knowing the dependencies of the alpha-factor leads to a better design of the aeration devices and, consequently, to a more efficient use of aeration energy. Applying the current state of knowledge about oxygen transfer leads to the conclusion that, in contrast to current opinion, simultaneous aerobic stabilization requires the same SOTR as conventional activated sludge systems with advanced nutrient removal, even though a higher organic load is degraded. PMID- 22049736 TI - Effect of diffusional mass transfer on the performance of horizontal subsurface flow constructed wetlands in tropical climate conditions. AB - The effect of mass transfer on the removal rate constants of BOD5, NH3, NO3 and TKN has been investigated in a Horizontal Subsurface Flow Constructed Wetland (HSSFCW) planted with Phragmites mauritianus. The plug flow model was assumed and the inlet and outlet concentrations were used to determine the observed removal rate constants. Mass transfer effects were studied by assessing the influence of interstitial velocity on pollutant removal rates in CW cells of different widths. The flow velocities varied between 3-46 m/d. Results indicate that the observed removal rate constants are highly influenced by the flow velocity. Correlation of dimensionless groups namely Reynolds Number (Re), Sherwood Number (Sh) and Schmidt Number (Sc) were applied and log-log plots of rate constants against velocity yielded straight lines with values beta = 0.87 for BOD5, 1.88 for NH3, 1.20 for NO3 and 0.94 for TKN. The correlation matched the expected for packed beds although the constant beta was higher than expected for low Reynolds numbers. These results indicate that the design values of rate constants used to size wetlands are influenced by flow velocity. This paper suggests the incorporation of mass transfer into CW design procedures in order to improve the performance of CW systems and reduce land requirements. PMID- 22049737 TI - Optimization of Fenton process for decoloration and COD removal in tobacco wastewater and toxicological evaluation of the effluent. AB - Decoloration and chemical oxygen demand (COD) removal in tobacco wastewater by Fenton process has been optimized under 25 +/- 2 degrees C. The results showed that the optimal range of conditions were pH 4.13-4.66, Fe(2+) 0.29-0.34 g/L and H2O2 > or = 2.73 g/L. Within this range, up to 95% of colour and 90% of COD was removed. In an enlarged system, setting the optimal conditions as pH 4.50, Fe(2+) 0.34 g/L and H2O2 4.00 g/L, the colour removal rate was 96.03 +/- 2.57%, with COD removal rate of 93.30 +/- 2.92%. The residual COD of 73.67 +/- 19.70 mg/L in effluent had hit the State's first-class standard for the industrial discharge in China (< 100 mg/L COD, GB8978-1996). The ecological safety of Fenton process has also been evaluated. When reaction completed, the content of hydroxyl free radical (OH) was 3.26 +/- 0.44 mg/L. There was no inhibition of Fenton effluent in growth of Escherichia coli, Pseudomonas putida, Pseudomonas sp. HF-1, Acinetobacter sp. TW and Sphingomonas sp. TY. No oxidative stress was induced on strain HF-1 by Fenton effluent. Thus, Fenton process was one of high-efficiency and ecologically safe strategy for tobacco wastewater advanced treatment. PMID- 22049738 TI - Respirometric assays of two different MBR (microfiltration and ultrafiltration) to obtain kinetic and stoichiometric parameters. AB - A comparison of two different medium scale MBRs (ultrafiltration and microfiltration) using respirometric methods has been achieved. The ultrafiltration membrane plant (0.034 microm pore size) maintained recirculation sludge flow at seven times the influent flow, and membranes were backwashed every 5 min and chemically cleaned weekly. The microfiltration membrane plant (0.4 microm pore size) maintained recirculation sludge flow at four times the influent flow, membrane-relax was applied after the production phase and membranes were chemically cleaned in the event of high trans-membrane pressure. Both technologies showed a similar performance with regard to heterotrophic kinetic and stoichiometric parameters and organic matter effluent concentrations. The influent was characterized by means of its COD fractions and the average removal percentages for COD concentrations were around 97% for both plants in spite of influent COD fluctuation, temperature variations and sludge retention time (SRT) evolution. Both SRT evolution and temperature affect the heterotrophic yield (Y(H)) and the decay coefficient (bH) in the same range for both plants. Y(H) values of over 0.8 mg COD/mg COD were obtained during the unsteady periods, while under steady state conditions these values fell to less than 0.4 mg COD/mg COD. bH by contrast reached values of less than 0.05 d(-1). PMID- 22049739 TI - On-site evaluation of the removal of 100 micro-pollutants through advanced wastewater treatment processes for reuse applications. AB - The next challenge of wastewater treatment is to reliably remove micro-pollutants at the microgram per litre range in order to meet reuse applications and contribute to reach the good status of the water bodies. A hundred priority and relevant emerging substances were measured to evaluate at full-scale the removal efficiencies of seven advanced treatment lines (one membrane bioreactor process and six tertiary treatment lines) that were designed for reuse applications. To reliably compare the processes, specific procedures for micro-pollutants were applied for sampling, analysis and calculation of removal efficiencies. The membrane bioreactor process allowed to upgrade the removal efficiencies of about 20% of the substances measured, especially those that were partially degraded during conventional processes. Conventional tertiary processes like high rate clarification, sand filtration and polishing pond achieved significant removal for some micro-pollutants, especially for adsorbable substances. Advanced tertiary processes, like ozonation, activated carbon and reverse osmosis were all very efficient to complete the removal of polar pesticides and pharmaceuticals; metals and less polar substances were better retained by reverse osmosis. PMID- 22049740 TI - Application of the material flow analysis method for evaluating strategic sanitation plan in Sub-Saharan Africa: the case of Fada N'Gourma-Burkina Faso. AB - In the context of rapid urbanization across Sub-Saharan Africa there is a critical need for more robust decision-making between different ways of providing sanitation services in existing and new peri-urban areas. In several countries, authorities tried to find solutions by developing strategies to address sanitation problems in the form of Strategic Sanitation Plans. In Burkina, Strategic Sanitation Plans have been elaborated and implemented since the 1990s. Fada N'Gourma, a secondary city in Burkina, also adopted a Strategic Plan for wastewater and excreta management in 2006. In this study we use material flow analysis as a decision making tool to verify technology options of the Plan. A model was developed and data was collected in order to assess material and nitrogen flows. The status quo situation was compared to scenario based on the proposals made in the Sanitation Plan. Results show that the technology options which were recommended improved human health in the short term. However, the options led to groundwater pollution in the medium term. Compared to the current situation, matter and nitrogen flows would increase by 7% and 7.4% respectively in groundwater. It is thus concluded that the proposed options will not achieve the Plan's stated objectives of environmental protection. PMID- 22049741 TI - Monitoring pH and ORP in a SHARON reactor. AB - This paper analyses the valuable information provided by the on-line measurements of pH and oxidation reduction potential (ORP) in a continuous single high ammonia removal over nitrite (SHARON) reactor. A laboratory-scale SHARON reactor equipped with pH, ORP, electric conductivity and dissolved oxygen (DO) probes has been operated for more than one year. Nitrogen removal over nitrite has been achieved by adding methanol at the beginning of anoxic stages. Time evolution of pH and ORP along each cycle allows identifying the decrease in nitritation rate when ammonia is consumed during the aerobic phase and the end of the denitrification process during the anoxic phase. Therefore, monitoring pH and ORP can be used to develop a real-time control system aimed at optimizing the length of both aerobic and anoxic stages. Real-time control of methanol addition can be carried out by using the information provided by these probes: excessive methanol addition in the anoxic stage is clearly detected in the ORP profile of the following aerobic phase, while a deficit of methanol is detected in both pH and ORP profiles of that anoxic phase. Moreover, other valuable information such as the amount of ammonia nitrified, failures in DO measurements, excessive stirring during the anoxic stage and methanol dosage in the aerobic phase was also provided by the pH and ORP profiles. PMID- 22049742 TI - Pre-ozonation in the activated sludge process: fate of nitrogen species. AB - The objective of this research was to include ozonation prior to an activated sludge treatment and investigate the effect on the nitrogen species, their fate and the consequences of this oxidation upon the biomass. Three parallel treatment systems were used: the base system, where feed went directly to the activated sludge reactor, and two others, where the influent was ozonated at two different dosages, 15 and 25 mg/L of influent, prior to the biological reactors. The results from the ozonation chamber show a high oxidation capacity of the entering ammonia and organic nitrogen, proportional to the ozone dose. The oxidation product was nitrate. No de-nitrification was expected because a high oxygen concentration (4 mg/L) was maintained in the reactors. The reactors receiving ozonated influent showed a lower assimilation of nitrogen by the biomass. The sludge nitrogen content resulted in 11, 9.3 and 7.4% dry-weight corresponding to no-ozone, low ozone and high ozone dosages, respectively. In spite of the lower ammonia available in the ozonated flows, the corresponding reactors showed a higher specific nitrification rate. The ozonated system also performed better in terms of chemical oxygen demand (COD) and biochemical oxygen demand (BOD5) removals, besides showing a higher true biomass yield coefficient. PMID- 22049743 TI - The impact of cost recovery and sharing system on water policy implementation and human right to water: a case of Ileje, Tanzania. AB - In Tanzania, the National Water Policy (NAWAPO) of 2002 clearly stipulates that access to water supply and sanitation is a right for every Tanzanian and that cost recovery is the foundation of sustainable service delivery. To meet these demands, water authorities have introduced cost recovery and a water sharing system. The overall objective of this study was to assess the impact of cost recovery and the sharing system on water policy implementation and human rights to water in four villages in the Ileje district. The specific objectives were: (1) to assess the impact of cost recovery and the sharing system on the availability of water to the poor, (2) to assess user willingness to pay for the services provided, (3) to assess community understanding on the issue of water as a human right, (4) to analyse the implications of the results in relation to policies on human rights to water and the effectiveness of the implementation of the national water policy at the grassroots, and (5) to establish the guidelines for water pricing in rural areas. Questionnaires at water demand, water supply, ability and willingness to pay and revenue collection were the basis for data collection. While 36.7% of the population in the district had water supply coverage, more than 73,077 people of the total population of 115,996 still lacked access to clean and safe water and sanitation services in the Ileje district. The country's rural water supply coverage is 49%. Seventy-nine percent of the interviewees in all four villages said that water availability in litres per household per day had decreased mainly due to high water pricing which did not consider the income of villagers. On the other hand, more than 85% of the villagers were not satisfied with the amount they were paying because the services were still poor. On the issue of human rights to water, more than 92% of the villagers know about their right to water and want it exercised by the government. In all four villages, more than 78% of the interviewees are willing to payforwater provided that the tariffs are affordable. Water policy implementation continues slowly: regardless of the fact that more than five years have passed since policy inception, 60% of the villagers in Itumba still have no water services at all. The study shows that government fulfilment of human rights to water has a long way to go, especially in rural areas where people cannot afford to pay for water and some of the villages still depend on water from wells and seasonal rivers. PMID- 22049744 TI - Influence of design, physico-chemical and environmental parameters on pharmaceuticals and fragrances removal by constructed wetlands. AB - The ability of several mesocosm-scale and full-scale constructed wetlands (CWs) to remove pharmaceuticals and personal care products (PPCPs) from urban wastewater was assessed. The results of three previous works were considered as a whole to find common patterns in PPCP removal. The experiment took place outdoors under winter and summer conditions. The mesocosm-scale CWs differed in some design parameters, namely the presence of plants, the vegetal species chosen (Typha angustifolia versus Phragmites australis), the flow configuration (surface flow versus subsurface flow), the primary treatment (sedimentation tank versus HUSB), the feeding regime (batch flow versus continuous saturation) and the presence of gravel bed. The full-scale CWs consisted of a combination of various subsystems (ponds, surface flow CWs and subsurface flow CWs). The studied PPCPs were ketoprofen, naproxen, ibuprofen, diclofenac, salicylic acid, carbamazepine, caffeine, methyl dihydrojasmonate, galaxolide and tonalide. The performance of the evaluated treatment systems was compound dependent and varied as a function of the CW-configuration. In addition, PPCP removal efficiencies were lower during winter. The presence of plants favoured naproxen, ibuprofen, diclofenac, salicylic acid, caffeine, methyl dihydrojasmonate, galaxolide and tonalide removal. Significant positive correlations were observed between the removal of most PPCPs and temperature or redox potential. Accordingly, microbiological pathways appear to be the most likely degradation route for the target PPCPs in the CWs studied. PMID- 22049745 TI - Redesigning wastewater infrastructure to improve resource efficiency. AB - Resource efficiency of wastewater management is a question of optimizing at the same time the management of resources in wastewater (e.g. water), the resources spent on treatment and transport (e.g. energy), the natural resources to protect (e.g. the receiving waters), and the anthropogenic resources (e.g. capital). For instance, wastewater can be treated to any given quality, but only at the expense of energy and investment costs. Today, many up-coming problems are solved incrementally, leading to resource consuming solutions optimized for water pollution control in well off countries, whereas large parts of the world have at the best very simple wastewater treatment. From a global point of view, a system change is necessary in order to solve the immense problems arising from global population growth, urban development and climate change. Source separation is a promising concept for resource efficient wastewater management, but a more concerted effort is necessary from the international community in order to develop competitive technologies and overcome the inflexibility of the present end-of-pipe technology. Much more research and development are necessary, not only in the area of engineering, but also with respect to the socio-economic dimensions, especially in the area of regulation, suitable governance and management models, and concerning the involvement of industrial partners. PMID- 22049746 TI - Experimental investigation on water treatment by the combined nano MgO nanofiltration technique. AB - A combined system using nano MgO and nanofiltration (NF) membrane was established to purify polluted water in this experiment. The turbidity, permanganate index, UVA254, colony counts and the concentrations of NO3-, NO2-, NH4+, Fe, Mn and Mg of the effluents from each unit of this combined system were measured to investigate the pollutant removal of this system. Based on the results obtained, the combined nano MgO-NF system could efficiently remove many kinds of pollutants in this experiment, including organic matter, nitrogen species, heavy metals, suspended solids and bacteria. And the effluents could meet the standard of drinking water. Furthermore, increasing the nano MgO dosage could not elevate the removal ratio of the pollutants, but only increase the Mg content of the effluent. Thus, 0.05 g L(-1) of nano MgO may be a suitable dosage for 2,000 L of polluted water treatment. Also, the operating pressure of NF membrane had no significant effect on pollutant removal when the operating pressure of NF membrane was increased from 0.3 to 0.9 MPa. PMID- 22049747 TI - Intensification of sonochemical degradation of phenol using additives at pilot scale operation. AB - The present work reports the use of sonochemical reactors for the degradation of phenol in the presence of additives with an objective of enhancing the rates of degradation at a pilot scale operation. Process intensification studies have been carried out using additives such as hydrogen peroxide (H2O2) (0.5-2.0 g/L), sodium chloride (0.5-1.5 g/L) and solid particles viz. cupric oxide (CuO) and titanium dioxide (TiO2) (0.5-2.5 g/L). Optimum concentration for H2O2 and sodium chloride has been observed beyond which no beneficial effects are obtained even with additional loadings. Maximum extent of degradation has been observed by using ultrasound/H2O2/CuO approach at a solid loading of 1.5 g/L followed by ultrasound/H2O2/TiO2 approach at a loading of 2.0 g/L. The obtained results at pilot scale operation in the current work are very important especially due to the fact that the majority of earlier studies are at laboratory scale which cannot provide the design related information for large scale operation as required scale up ratios are quite high adding a degree of uncertainty in the design. The novelty of the present work lies in the fact that it highlights successful application of sonochemical reactors for wastewater treatment at pilot scale operation. PMID- 22049748 TI - Investigating the spatial-temporal variation of nitrogen cycling in an urban river in the North China Plain. AB - Urban rivers are essential in retaining nutrients, but little is known about nitrogen cycling in these rivers in semiarid areas. We measured chemical and isotopic compositions of ammonium (NH4(+)-N) and nitrate (NO3(-)-N) to investigate spatial-temporal variation of nitrogen cycling in the Fuhe River in the North China Plain. Nitrogen pollution in the river was mainly induced by extra NH4(+)-N inputs which come from the discharges of urban sewage and effluents of wastewater treatment plants in upstream. NH4(+)-N obtained from decomposing organic matter of sediments can diffuse into the overlying water. Intense nitrification then occurs at the terrestrial-aquatic interface. Due to less vegetation in spring and autumn, loss of NH4(+)-N is mainly caused by nitrification. In contrast, significant NH4(+)-N is absorbed by plants in summer. NO3(-)-N generated from nitrification can be denitrified during the study period. The highest NO3(-)-N loss (about 86.3%) was observed in summer. The contribution of NO3(-)-N loss due to denitrification is 44.6%. The remaining 55.4% is due to plant uptake. The results suggested that nitrogen cycling in the river is related to temperature and dry-wet cycles. And vegetation restoration along the river could benefit the incremental improvements to the aquatic ecosystem. PMID- 22049749 TI - Several natural indicators of radial well ageing at the Belgrade groundwater source, part 1. AB - Over time, the radial collector wells of the Belgrade Groundwater Source, located in the alluvial sediments of the Sava River, exhibit a decline in discharge and a reduction in operating efficiency due to well ageing. An increase in hydraulic losses at the lateral screens, due to chemical and biochemical clogging, has been identified as the primary cause. Certain hydrogeological, hydrochemical and microbiological parameters reflect the well-ageing process and can, therefore, be considered as its indicators. An indicator-based determination of scale is an important aspect in the selection of appropriate well locations, structural characteristics, and maintenance approaches. Well ageing was studied over a period of 5 years (2005-2009). The objective was to investigate the causes of well ageing. The correlations established between the groundwater redox potential, the total iron concentration in groundwater, the grain-size distribution of the aquifer, and well discharge, are presented in the paper. PMID- 22049750 TI - Several natural indicators of radial well ageing at the Belgrade groundwater source, part 2. AB - From 2005 to 2009, research was conducted at the Belgrade Groundwater Source (BGWS) to investigate the process of clogging of wells with horizontal lateral screens (radial wells). The clogging process was monitored via the kinetics of the increase in hydraulic losses at the laterals. A correlation of this process with the redox potential, the iron concentration in water, and the microbial population growth at the laterals and in their immediate vicinity was established. Research outcomes are presented here from a study of five wells where laterals were replaced between 2006 and 2008. Derived dependencies were later used to define the preferred approach to the installation and maintenance of well laterals at the BGWS. Results contribute to the study of well ageing caused by biochemical clogging. PMID- 22049751 TI - Combination of batch experiments with continuous reactor data for ADM1 calibration: application to anaerobic digestion of pig slurry. AB - Modelling anaerobic digestion processes is a key aspect of studying and optimizing digesters and related waste streams. However, for the satisfactory prediction of biogas production and effluent characteristics, some parameters have to be calibrated according to the characteristics of the substrates. This article describes a calibration procedure for the IWA 'Anaerobic Digestion Model no. 1' applied to the modelling of a digester for treatment of pig slurry. The most sensitive parameters were selected and calibrated combining results from a continuous digester and from batch trials run with the sludge sampled from the digester and the addition of specific substrates. According to the sensitivity analysis, acetoclastic methanogenesis, acetogenesis of propionate and acidogenesis of sugars were identified as the main sensitive steps in our case. The calibration procedure led us to modify slightly acetogenesis of propionate kinetic. However, acetoclastic methanogenesis and acidogenesis of sugars kinetics were significantly reduced by decreasing km and increasing Ks. Indeed, for instance, a decrease of km_ac from 8 to 7 day(-1) combined with an increase of Ks_ac from 0.15 to 1.5 kgCOD/m3 was necessary. After calibration, ADM1 provides an accurate simulation of the continuous reactor results. PMID- 22049752 TI - Dual-electrode oxidation used for aniline degradation in aqueous electrolyte. AB - The electrochemical degradation of aniline in aqueous electrolyte has been studied by dual-electrode oxidation process using Ti/SnO2-Sb2O5 for anodic oxidation and graphite cathode to produce H2O2 in situ. The linear voltammograms were employed to obtain reasonable anodic and cathodic potential values for the purpose of restraining side reactions. The influence of Fe2+ on aniline degradation was investigated under potentiostatic condition with a three electrode system. It was found that an anodic potential range of 2.0 +/- 0.1 V and a cathodic potential of -0.65 V could favor anodic oxidation and H2O2 generation. Anodic oxidation was accounted for aniline degradation in the absence of Fe2+, while in the presence of Fe2+ both electro-Fenton oxidation and anodic oxidation (dual-electrode oxidation) could degradate aniline effectively. When cathodic potential values were -0.65 and -0.80 V, the optimum Fe2+ concentration were 0.50 and 0.30 mM, respectively. 77.5% COD removal and 70.4% TOC removal with a current efficiency (CE) of 96-100% were achieved under the optimum conditions. This work indicates that dual-electrode oxidation process characterized by a high CE is feasible for the degradation of organic compounds. PMID- 22049753 TI - Zn and Pb emissions from roofing materials--modelling and mass balance attempt at the scale of a small urban catchment. AB - Many studies have shown that roofing materials are an important source of metals in urban runoff. Today, in the context of the European Water Directive (2000/60 CE), the quantification of these emissions is necessary, and thus the development of assessment tools is needed. This study focuses on a small urban catchment (drained by a separative sewer system). Atmospheric fallout, road runoff, roof runoff and total runoff at the outlet of the catchment were sampled. The aim is (1) to verify the contribution of roofing materials to metallic flows of Zn and Pb at the catchment scale and (2) to try to model emissions using some models previously developed at the test-bed scale. These models have to be tested at different spatial scales. Results obtained confirm the strong contribution of roofing materials to Zn and Pb flows at the catchment scale. For Zn, models tested were successfully transposed and validated at the roof and the catchment scales, permitting a good quantification of Zn emissions. For Pb, the use of the models highlights some difficulties, especially concerning the identification and the quantification of lead surface areas implemented. PMID- 22049754 TI - Cost effectiveness of centralised and decentralised storm water treatment. AB - As part of a research & development project commissioned by the Land of North Rhine-Westphalia's Ministry for the Environment and Nature Conservation, Agriculture and Consumer Protection (MUNLV) an examination is being carried out of the general possibilities for centralised and decentralised treatment storm water runoff to be discharged into (canalised) receiving waters and the costs ensuing from this. The examination of the different options is being carried out under real conditions, with the Briller Creek (Wuppertal/Germany) and Muggen Creek (Remscheid/Germany) catchment areas being used as models. The range of investigations deals with a comparison between 'decentralised, semicentralised, centralised' storm water treatment, centralised storm water treatment involving a separate sewer and parameter-specific pollution based storm water runoff control. In the framework of the research project each of the variants is to be elaborated and the costs are to be calculated so as to permit a comparison between the different system designs. In particular, the investigations are to take into account the actual requirements to be met by storm water drainage systems involving separate sewage systems. PMID- 22049755 TI - Potential of UV/H2O2 oxidation for enhancing the biodegradability of municipal reverse osmosis concentrates. AB - UVC/H2O2 and VUV/H2O2 oxidation processes were evaluated for the degradation of organic pollutants in reverse osmosis concentrate (ROC) produced from a municipal secondary effluent. It was found that the oxidation by UVC/H2O2 and VUV/H2O2 processes could be described as a pseudo first-order reaction. For UVC increased oxidation occurred with increasing H2O2 dosage up to 2 mM above which improvement in oxidation performance decreased. At the same H2O2 dosage, VUV irradiation gave better overall oxidation performance. Compared with UVC/6 mM H2O2, VUV/2 mM H2O2 gave a greater rate of reduction of chemical oxygen demand, but a lower rate for reduction of dissolved organic carbon, suggesting that oxidation of organics by the two methods followed different pathways. The change of absorbance at 254 nm and fluorescence excitation emission matrix spectra of irradiated samples indicated that the large and complex compounds were fragmented rapidly by the *OH, resulting in rapid decolourisation. The biodegradability of the organics in the ROC was increased from 11% to 35% after 1 h treatment by UVC/3 mM H2O2, whereas a greater increase (41%) was obtained with VUV/2 mM H2O2. This increase in biodegradability indicates the potential for employing a subsequent biological treatment process. PMID- 22049756 TI - Enhancing the removal of arsenic, boron and heavy metals in subsurface flow constructed wetlands using different supporting media. AB - The presence of arsenic and heavy metals in drinking water sources poses a serious health risk due to chronic toxicological effects. Constructed wetlands have the potential to remove arsenic and heavy metals, but little is known about pollutant removal efficiency and reliability of wetlands for this task. This lab scale study investigated the use of vertical subsurface flow constructed wetlands for removing arsenic, boron, copper, zinc, iron and manganese from synthetic wastewater. Gravel, limestone, zeolite and cocopeat were employed as wetland media. Conventional gravel media only showed limited capability in removing arsenic, iron, copper and zinc; and it showed virtually no capability in removing manganese and boron. In contrast, alternative wetland media: cocopeat, zeolite and limestone, demonstrated significant efficiencies--in terms of percentage removal and mass rate per m3 of wetland volume--for removing arsenic, iron, manganese, copper and zinc; their ability to remove boron, in terms of mass removal rate, was also higher than that of the gravel media. The overall results demonstrated the potential of using vertical flow wetlands to remove arsenic and metals from contaminated water, having cocopeat, zeolite or limestone as supporting media. PMID- 22049757 TI - Effects on evaporation rates from different water-permeable pavement designs. AB - The urban water balance can be attenuated to the natural by water-permeable pavements (WPPs). Furthermore, WPPs have a 16% higher evaporation rate than impermeable pavements, which can lead to a better urban climate. Evaporation rates from pavements are influenced by the pavement surface and by the deeper layers. By a compared evaporation measurement between different WPP designs, the grain size distribution of the sub-base shows no influence on the evaporation rates in a significant way. On the contrary, a sub-base made of a twin-layer decreases the evaporation by 16% compared to a homogeneous sub-base. By a change in the colour of the paving stone, 19% higher evaporation rates could be achieved. A further comparison shows that the transpiration-effect of the grass in grass pavers increases the evaporation rates more than threefold to pervious concrete pavements. These high evapotranspiration rates can not be achieved with a pervious concrete paving stone. In spite of this, the broad field of application of the pervious concrete paving stone increases the importance in regard to the urban climate. PMID- 22049758 TI - Real-time control of sewer systems using turbidity measurements. AB - Real-time control (RTC) of urban drainage systems has been proven useful as a means to reduce pollution by combined sewer overflow discharges. So far, RTC has been investigated mainly with a sole focus on water quantity aspects. However, as measurement techniques for pollution of wastewater are advancing, pollution-based RTC might be of increasing interest. For example, turbidity data sets from an extensive measurement programme in two Paris catchments allow a detailed investigation of the benefits of using pollution-based data for RTC. This paper exemplifies this, comparing pollution-based RTC with flow-based RTC. Results suggest that pollution-based RTC indeed has some potential, particularly when measurements of water-quality characteristics are readily available. PMID- 22049759 TI - Climate change tendencies observable in the rainfall measurements since 1950 in the federal land of North Rhine-Westphalia and their consequences for urban hydrology. AB - Climate change is present in climatological models - but did we already observe changes in the past measurement data? For the state of North Rhine Westphalia, the rainfall measurements since 1950 have been systematically analysed in order to find out whether there have already been trends and whether the behaviour of rainfall has changed in time. More than 600 station series have been screened for use in the project and quality controlled. Implausible data were discarded. For the analysis, standard values such as yearly sums, half-yearly sums, monthly sums, number of dry days, number of days with precipitation above a threshold, partial time series and extreme values statistics have been calculated and evaluated. Results show that also in the past 50 years, changes in precipitation regime could be observed. These changes have been regionally different. Consequences for urban hydrology include a development of more flexible design approaches. PMID- 22049760 TI - Uncertainty evaluation of design rainfall for urban flood risk analysis. AB - A reliable and long dataset describing urban flood locations, volumes and depths would be an ideal prerequisite for assessing flood frequency distributions. However, data are often piecemeal and long-term hydraulic modelling is often adopted to estimate floods from historical rainfall series. Long-term modelling approaches are time- and resource-consuming, and synthetically designed rainfalls are often used to estimate flood frequencies. The present paper aims to assess the uncertainty of such an approach and for suggesting improvements in the definition of synthetic rainfall data for flooding frequency analysis. According to this aim, a multivariate statistical analysis based on a copula method was applied to rainfall features (total depth, duration and maximum intensity) to generate synthetic rainfalls that are more consistent with historical events. The procedure was applied to a real case study, and the results were compared with those obtained by simulating other typical synthetic rainfall events linked to intensity-duration-frequency (IDF) curves. The copula-based multi-variate analysis is more robust and adapts well to experimental flood locations even if it is more complex and time-consuming. This study demonstrates that statistical correlations amongst rainfall frequency, duration, volume and peak intensity can partially explain the weak reliability of flood-frequency analyses based on synthetic rainfall events. PMID- 22049761 TI - Monitoring the variations of the oxygen transfer rate in a full scale membrane bioreactor using daily mass balances. AB - Oxygen transfer in biological wastewater treatment processes with high sludge concentration, such as membrane bioreactor (MBR), is an important issue. The variation of alpha-factor versus mixed liquor suspended solids (MLSS) concentration was investigated in a full scale MBR plant under process conditions, using mass balances. Exhaustive data from the Supervisory Control And Data Acquisition (SCADA) and from additional online sensors (COD, DO, MLSS) were used to calculate the daily oxygen consumption (OC) using a non-steady state mass balance for COD and total N on a 24-h basis. To close the oxygen balance, OC has to match the total oxygen transfer rate (OTRtot) of the system, which is provided by fine bubble (FB) diffusers in the aeration tank and coarse bubbles (CB) in separate membrane tanks. First assessing OTR(CB) then closing the balance OC = OTRtot allowed to calculate OTR(FB) and to fit an exponential relationship between OTR(FB) and MLSS. A comparison of the alpha-factor obtained by this balance method and by direct measurements with the off-gas method on the same plant is presented and discussed. PMID- 22049762 TI - Performance of infiltration swales with regard to operation in winter times in an Alpine region. AB - In cold climate regions winter conditions significantly influence the performance of stormwater infiltration devices. Frozen soil and water storage by snow changes their operation. In this paper winter operation of a grassed infiltration swale was investigated using on-site and laboratory measurements. The field investigation of a grassed swale at a parking place in an Alpine region showed that the swale fulfilled its function properly. Although the top layer was frozen for some time, the storage capacity of the swale was sufficient to store the precipitation until the conditions improved. The soil attenuated the air temperature, at 20 cm below ground surface the soil was only frozen for one week. winter maintenance proved to be a problem, together with the snow from the parking place a lot of gravel and fine particles were deposited at one end of the swale. This decreased the hydraulic conductivity at that point significantly. The laboratory tests with soil columns showed an increase of flow time through the soil column with decreasing soil moisture content. For soil temperatures below 0 degrees C the hydraulic conductivity was reduced for increasing initial soil moisture contents. All in all the hydraulic conductivity was best around 0 degrees C for all soil water contents. However, also at minus 5 degrees C the coefficient of hydraulic conductivity was always at least above 10(-6) m/s, thus within the range of tolerated hydraulic conductivity specified in the national guidelines. Nevertheless, the handling of the soil was found to have high influence on the results. The results indicate that in the Alpine region infiltration swales operate sufficiently under winter conditions although with decreased performance. PMID- 22049763 TI - Methodologies to study the surface hydraulic behaviour of urban catchments during storm events. AB - A good knowledge of the hydraulic behaviour of an urban catchment and its surface drainage system is an essential requirement to guarantee traffic and pedestrian safety. In many cases, inlets have been situated according to spatial density criteria. Indeed a more rational location of inlets on urban catchments must be defined according to an accurate analysis of the relationship between street flow and inlet hydraulic efficiency. Moreover we lack specific hazard criteria in terms of the maximum acceptable flow depths and velocities on the streets that do not cause problems to pedestrians. In this paper the results of two different experimental campaigns are presented. The first was carried out to evaluate inlet hydraulic efficiency; the second was carried out to address the pedestrian stability in urban flood conditions, whose aim was to propose new hazard criteria. On the basis of the experimental results, a methodology was developed to assess flood hazard in urban areas during storm events. If a refined topographic representation of urban areas is available, a two-dimensional numerical simulation of urban flooding can be performed using complete shallow water equations. According to this approach a numerical application for flood hazard assessment in a street of Barcelona is shown. PMID- 22049764 TI - Analysis of enterovirus and adenovirus presence in swimming pools in Cyprus from 2007-2008. AB - An analysis was carried out to determine the presence of enteroviruses and adenoviruses in public swimming pools in Cyprus. The effectiveness of the commonly implemented disinfection procedure of chlorination was confirmed by determination of bacteriological markers. Analysis of viral presence was carried out by sampling random swimming pools from the five major cities in Cyprus during a period of 21 months spanning from April 2007 to December 2008. A 10 I sample was taken from each swimming pool to be tested and was subsequently concentrated via membrane filtration using a new methodological approach for virus elution. Concentrated samples were analysed using of a Real Time Polymerase Chain Reaction (PCR) TaqMan probe based approach to detect the presence of enteroviruses and adenoviruses. Over the period of 21 months a total of 126 swimming pools were sampled and analysed. In four swimming pools enteroviruses were detected, in one pool echovirus 18 was identified, in two pools echovirus 30 was identified and in one other pool poliovirus Sabin 1 was identified. Similarly, in four swimming pools adenoviruses were detected, in all four adenovirus 41 was identified. Bacteriological marker analysis showed that 98% of pools complied with Cyprus regulations. PMID- 22049765 TI - A new strategy for determination of current efficiency during electro-oxidation of aromatic compounds in a packed-bed system. AB - The electro-oxidation of aromatic compounds in 4,4'-diaminostilbene-2,2' disulfonic (DSD) acid wastewater on IrO2-Ta2O5/Ti anodes was studied. The current efficiency was evaluated in terms of chemical oxygen demand (COD) by introducing a new factor, the fraction of the Faradaic current to the total cell current (beta) through the network analysis of packed bed electrode system (PBEs). Experimental results using an up-flow PBEs at current intensities ranging from 5 to 16 A m(-2), flow rates ranging from 20 to 80 L h(-1) and inter-electrode distance of 5 to 50 cm are in good agreement with the proposed equation. In addition, lower current density, increasing flow rate and larger inter-electrode distance are beneficial to enhance the current efficiency. PMID- 22049766 TI - Seasonal factors influencing the failure of buried water reticulation pipes. AB - While the use of environmental factors in the analysis and prediction of failures of buried reticulation pipes in cold environments has been the focus of extensive work, the same cannot be said for failures occurring on pipes in other (non freezing) environments. A novel analysis of pipe failures in such an environment is the subject of this paper. An exploratory statistical analysis was undertaken, identifying a peak in failure rates during mid to late summer. This peak was found to correspond to a peak in the rate of circumferential failures, whilst the rate of longitudinal failures remained constant. Investigation into the effect of climate on failure rates revealed that the peak in failure rates occurs due to differential soil movement as the result of shrinkage in expansive soils. PMID- 22049767 TI - Nitrate removal using different carbon substrates in a laboratory model. AB - Agricultural fields have been frequently identified as major contributors of nitrate leaching into surface and ground waters. Tile drains can act as direct pathways, transferring leached nitrate to surface water. Bioreactor filters are useful for the removal of nitrate from drainage waters; however, these filters require an external carbon supply to sustain denitrification. In this study, four organic carbon sources including wood, barley straw, rice husks, and date palm leaf, were used to enhance denitrification and the effects of water velocity and influent nitrate concentration on the nitrate removal were evaluated. Cumulative nitrate removal was highest for the date palm leaf treatments and was lowest for the wood treatments. The effects were in decreasing order for date palm leaf, barley straw, rice husks, and wood, respectively. The performance of the biofilters improved with increasing influent nitrate concentration and decreasing water velocity, allowing for high nitrate removal rates to be achieved. The results showed that all of the treatments had reduced the effluent nitrate concentrations below the USEPA maximum contaminant level for drinking water of 45 mg L(-1) nitrate at the end of the study. PMID- 22049768 TI - Exploring fecal indicator bacteria in a constructed stormwater wetland. AB - Microbial pollution in surface waters is a concern throughout the world, with both public health and economic implications. One contributing source to such pollution is stormwater runoff, often treated using various types of stormwater control measures. However, relatively little is known regarding microbe sequestration in constructed stormwater wetlands (CSWs), one type of commonly installed stormwater control measure. In this study, indicator bacteria concentrations in both the water and sediment of a CSW were evaluated at multiple locations. Results suggested that fecal coliform concentrations in stormwater runoff decrease through the system, with relatively consistent concentrations noted throughout the second half of the wetland. This potentially indicates a baseline concentration of fecal coliform is present due to internal processes such as animal activity and microbial persistence. However, wetland sediments showed little E. coli present during most sampling events, with minimal patterns existing with respect to sediment sampling location. CSW designs should promote optimization of hydraulic retention time and minimization of stormwater velocities to promote sedimentation and degradation of microbes by way of wetland treatment functions. PMID- 22049769 TI - Treatment of petroleum refinery wastewater by distillation-assisted catalytic oxidation under low temperature and low pressure. AB - A distillation-assisted catalytic oxidation (DACO) process under low temperature (100 degrees C) and atmospheric pressure was investigated to treat heavily contaminated wastewater from oil refining industry. The DACO experiments were carried out in a distillation batch reactor, using CuO/gamma-A1(2)O3 as catalyst. The experimental temperature was kept at 100 degrees C and H2O2 oxidant was supplied into the reactive system with 200 mL/L. The results demonstrated that more than 92.2% of chemical oxygen demand removal was obtained and the absorbance of the refinery wastewater after treatment was zero, indicating significant decolorization efficiency for the solution. The research of life and stability showed that the catalyst had a good stability. The present study indicates that this DACO approach may have a significant application potential for industrial wastewater treatment. PMID- 22049770 TI - Phosphorus removal by laboratory-scale unvegetated vertical-flow constructed wetland systems using anthracite, steel slag and related blends as substrate. AB - This research aimed to investigate the phosphorus (P) removal of a series of laboratory-scale unvegetated vertical-flow constructed wetland systems using anthracite, steel slag and related blends as substrate in treatment of low concentration domestic sewage. The long-term performance of P removal was firstly studied by using single substrate of anthracite or steel slag, and three systems applying various combined substrates were investigated when the average P loading rate varied between 0.9 and 1.5 g TP/m2 x d. The results demonstrated that both anthracite and steel slag systems were highly effective in removing total P (CTP, 77.17 +/- 23.34% and 90.26 +/- 4.48%) and soluble reactive P (SRP, 92.14 +/- 12.56% and 96.20 +/- 2.58%). The system filled with anthracite, vermiculite and steel slag from the top down removed 82.45 +/- 9.52% and 87.83 +/- 8.58% of TP and SRP, respectively. However, other combined substrate systems showed comparative low and fluctuant P removal. The effluent pH was maintained at 7-9, which met environmental requirements of China. Therefore, anthracite provides a long-term high efficiency of P removal and may be a promising substrate from the standpoint of the effluent pH, and the arrangement of combined substrate has a prominent effect on P removal. PMID- 22049771 TI - Quality assessment of rooftop runoff and harvested rainwater from a building catchment. AB - A major obstacle to the promotion of rainwater harvesting is chemical and microbiological concerns. To determine its suitability as an alternative water resource, water quality parameters such as pH, turbidity and metal ion concentrations and counted total coliform, Escherichia coli and heterotrophic bacteria were measured. It was observed that the stored rainwater had a neutral average pH and that its turbidity depended on the duration and intensity of the rainfall event. Metal concentrations were within the permissible limits specified in the Korea drinking water standard. In addition, counts of coliform, E. coli and heterotrophic bacteria were higher in the first flush 5 min after the start of the rainfall event. Principal component analysis and correlation analysis through 40 events in 2009 showed that the quality of stored rainwater depends on the conditions of the catchment and storage tank and the antecedent dry period. PMID- 22049772 TI - Electrochemical treatment of residual ammonia nitrogen in biologically pretreated coking wastewater with three-dimensional electrodes. AB - The electrochemical oxidation of the residual ammonia nitrogen contained in biologically pretreated coking wastewater using three-dimensional electrode system was studied. The results show the Ti/RuO2/IrO2 anode plates and the coke have good surface characteristics for the purpose of this study. In addition, studies also show that the three-dimensional electrode system should be able to give a satisfied solution to the residual bio-refractory ammonia nitrogen in biologically pretreated coking wastewater in comparison to conventional two dimensional electrodes. At coke size of 10-20 mesh, electrode distance of 1.0 cm and current density of 4.5 mA/cm2, the residual ammonia nitrogen in the three dimensional electrode system was almost completely removed in 60 min. PMID- 22049773 TI - Removal of micropollutants and NOM in carbon nanotube-UF membrane system from seawater. AB - One of the main problems for seawater reverse osmosis desalination is membrane fouling associated with natural organic matter. Bisphenol-A (BPA) and 17alpha ethinylestradiol (EE2) are well-known endocrine-disrupting compounds that have been detected in wastewater and seawater. In this study, the contribution of carbon nanotubes (CNTs, single-walled carbon nanotubes) to membrane fouling control and the potential adsorption mechanisms of BPA and EE2 were investigated using artificial seawater (ASW) in a bench scale ultrafiltration (UF) membrane coupled with CNTs. For high ionic strength ASW, UVA254 nm is a good alternative for highly aromatic dissolved organic carbon (DOC) determination, with a very strong linear relationship (R2 > or = 0.99) with increasing DOC concentrations. Approximately 80% of DOC in ASW was rejected by the CNT-UF system where 31% of DOC was removed due to adsorption by CNTs. The presence of CNTs shows a 20% increase in membrane flux in ASW. A strong linear correlation between retention and adsorption of BPA and EE2 was obtained. The percentage of adsorption/retention of BPA and EE2 in UF-CNTs follows the order: 94.0/96.6 (DI + CNTs, EE2) > 86.2/90.0 (ASW + CNTs, EE2) > 73.6/78.9 (DI + CNTS, BPA) > or = 74.1/77.3 (ASW + CNTS, BPA) > 29.8/29.8 (ASW, EE2) approximately equal to 27.3/27.3 (ASW, BPA) > or = 25.3/25.3 (DI, EE2) approximately equal to 24.8/24.8 (DI, BPA). This indicates that retention by the UF-CNT system is mainly due to adsorption. Overall, EE2 adsorption was greater than BPA during the UF-CNT experiments, presumably due to the higher hydrophobicity of EE2 than BPA. PMID- 22049774 TI - Presence, molecular characteristics and geosmin producing ability of actinomycetes isolated from South Korean terrestrial and aquatic environments. AB - The unpleasant odor of drinking water is one of the major problems in many water utilities in the world. Actinomycetes have long been associated with odorous compounds. Considering the paucity of research on Actinomycetes producing odorous compounds in South Korea, presence of Actinomycetes, their molecular characteristics and ability to produce odorous compounds were investigated in this study. Findings confirmed the presence of Actinomycetes in surface soil, sediment, and water samples from four sites: two artificial lakes [Paldang and Cheongpyeong (CP)], and two streams [Gyeongan (GA) and Yangpyeong]. Surface soil and sediment from CP area had the greatest concentration of Actinomycetes (8.2 x 10(7) and 6.8 x 10(6) colony forming units (CFUs)/gram, dry weight, respectively). When water samples are considered, samples from GA had the highest concentration (1.9 x 10(2) CFU/mL). 16S rRNA sequencing and molecular phylogenetic analysis showed that Streptomyces was the dominant genus (64.1%). In addition, the isolated Actinomycetes synthesized 5.4 ng/L geosmin as demonstrated by thermal desorption unit-gas chromatograph/mass spectrometry analysis. PMID- 22049775 TI - Enhanced biodegradation of 4-aminobenzenesulfonate in membrane bioreactor by Pannonibacter sp. W1. AB - 4-Aminobenzenesulfonate (4-ABS), an aromatic amine and recalcitrant toxic pollutant, is widely used in the dye and pharmaceutical industry. Pannonibactersp. W1 is a specialized microbial strain which can efficiently degrade 4-ABS. This study shows the feasibility of using the specialized strain in an MBR system to treat synthetic wastewater containing large amount of 4-ABS. Due to membrane retention, the biomass concentration is able to reach 5 g/L within two months of continuous operation. Pannonibacter sp. W1 is able to adapt to the high loading rate of 1000 mg 4-ABS/L and achieve a remarkable 4-ABS removal efficiency of 99% within 6 h. Strain W1 grows well under the MBR continuous operation and remains as the dominant bacterium at the end of 60 days continuous operation. Minor membrane fouling has been detected within 40 days of operating at 15 LMH. At a flux of 25 LMH, the system experiences the 'TMP jump'. The high organic removal rate and low membrane fouling results illustrate the excellent performance of the bioaugmented MBR system in 4-ABS wastewater treatment. PMID- 22049776 TI - Energy and phosphorus recovery from black water. AB - Source-separated black water (BW) (toilet water) containing 38% of the organic material and 68% of the phosphorus in the total household waste (water) stream including kitchen waste, is a potential source for energy and phosphorus recovery. The energy recovered, in the form of electricity and heat, is more than sufficient for anaerobic treatment, nitrogen removal and phosphorus recovery. The phosphorus balance of an upflow anaerobic sludge blanket reactor treating concentrated BW showed a phosphorus conservation of 61% in the anaerobic effluent. Precipitation of phosphate as struvite from this stream resulted in a recovery of 0.22 kgP/p/y, representing 10% of the artificial phosphorus fertiliser production in the world. The remaining part of the phosphorus ended up in the anaerobic sludge, mainly due to precipitation (39%). Low dilution and a high pH favour the accumulation of phosphorus in the anaerobic sludge and this sludge could be used as a phosphorus-enriched organic fertiliser, provided that it is safe regarding heavy metals, pathogens and micro-pollutants. PMID- 22049777 TI - Security lapses. Critics urge execs to take safety issues more seriously. AB - Violence in hospitals remains high a year after the Joint Commission's Sentinel Event Alert for it, but experts say CEOs can reduce violence by encouraging staff to report incidents and planning for when the unthinkable strikes. "I think we'd all be better served to give a little more forethought to what you would do if that kind of event takes place," says David Banks, left, of Forida Hospital. PMID- 22049778 TI - Trade bill hits QIOs. Program being regionalized as a funding offset. PMID- 22049779 TI - SSteady gains in quality ... but some insurers still won't publicly report data. PMID- 22049780 TI - Bridging the divide. RUC recommends payment for care coordination. PMID- 22049781 TI - Full of potential. List highlights healthcare innovations for 2012. PMID- 22049782 TI - Plenty of green in gray market. There's more at issue than just inflated prices for drugs in short supply. PMID- 22049783 TI - Playing well together. Bundled payments answer call for incentives to better coordinate care. PMID- 22049784 TI - Role call. COOs have seen their responsibilities shift and expand with changes in healthcare and growing demands on the chief executive. PMID- 22049785 TI - Taking hybrid ORs to heart. New facilities bring marriage of diagnostic imaging and cardiac surgery. PMID- 22049786 TI - [Reconstructed seminiferous tubules from ectopic grafting of testicular cells]. AB - OBJECTIVE: To investigate the ectopic grafts of mouse testicular cells by observing the reconstruction of seminiferous tubules, colonization of spermatogenic cells and spermatogenesis using immunodeficient mice as recipients. METHODS: The testes of newborn male ICR mice were digested to obtain single cell suspension. The cells were then mixed with matrigel and subcutaneously grafted into the dorsal region of the male nude mice. The mice were castrated after the operation and the grafts were dissected from 5 of the nude mice at 4, 6, 8 and 10 weeks, respectively. The success rates of transplantation and the graft diameters were calculated, and the structure of the reconstituted seminiferous tubules, colonization of the germ cells and spermatogenesis were observed by HE staining and immunohistochemistry. RESULTS: All the mice recipients survived after the testicular cell transplantation. Within 10 weeks after the operation, tissue masses could be observed, with the diameter increased from (3.91 +/- 0.71) mm at 4 weeks to (6.69 +/- 0.50) mm. Neovascularization was detected at the surface of the masses and seminiferous tubule structures found in the grafts. The germ cells that developed from spermatogonia to round spermatids were observed, but with no sperm in the tubules. Germ cells, Sertoli cells and Leydig cells were identified by immunochemical detection of Mvh, Gata4 and P450Scc in the grafts at 8 weeks. CONCLUSION: Seminiferous tubules could be ectopically reconstructed from suspension of neonatal mouse testicular cells. Ectopic grafting provided a preferable model for the studies on testis tissue engineering and interactions between testicular cells during testicular development and spermatogenesis. PMID- 22049787 TI - [Impact of unilateral acute testicular ischemia on the contralateral testis of rabbits in anesthetic and conscious states]. AB - OBJECTIVE: To compare the impact of unilateral acute testicular ischemia on the hemodynamics and histology of the contralateral testis of the rabbits under consistent anesthesia with that of the rabbits in the conscious state. METHODS: Forty-two healthy male white rabbits were randomly divided into an anesthetic group (Group A) to receive injection of sodium pentobarbital (PS) and a non anesthetic group (Group B), each including a control group of 5 animals (A0 and B0), an incomplete testicular ischemia group of 8 (A1 and B1), and a complete testicular ischemia group of 8 (A2 and B2). Testicular ischemia models were constructed by color Doppler ultrasonography. Contrast-enhanced ultrasound (CEUS) was used to observe the perfusion of the contralateral testes before and after ligating and loosening the unilateral spermatic cord in each experimental group. The control animals also underwent CEUS and measurement of the heart rate (HR) and blood pressure (BP) at the corresponding time. Histological structure changes in the contralateral testes of the rabbits were observed in both anesthetic and conscious states. RESULTS: PS anesthesia markedly suppressed the HR and BP of the rabbits. The parameters in Groups of A0, A1 and A2 showed no statistically significant changes after unilateral ligation of the spermatic cord, while Groups B1 and B2 displayed significantly decreased peak-base difference (PBD) and prolonged arrival time (AT) and half time of descending peak intensity (HT). Groups A1, B1 and B2 showed significantly increased PBD and prolonged HT shortly after loosening the spermatic cord. Focal pathological and ultrastructural changes were observed in the contralateral testes of the ischemic rabbits, but no significant difference was found in Johnson's score in comparison with the controls. The apoptotic cells were remarkably increased in Groups A1, B1 and B2. CONCLUSION: Acute testicular ischemia may induce injury to the contralateral testis to some degree, and a reflexive sympathetic response may cause hemodynamic changes in the non-anesthetic state. And the neural and vascular inhibitory effects of anesthesia could make insignificant changes of blood perfusion in the contralateral testis. PMID- 22049788 TI - [Relationship between vitamin D receptor gene Fok I polymorphisms and benign prostatic hyperplasia complicated by histological prostatitis]. AB - OBJECTIVE: To investigate the relationship between vitamin D receptor (VDR) gene Fok I polymorphisms and BPH complicated by histological prostatitis (BPH + HP). METHODS: We detected Fok I polymorphisms in the peripheral blood of 79 patients with BPH + HP and 81 controls with BPH only using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and analyzed the frequency distribution of the genotypes and alleles of the two groups of patients. RESULTS: Obvious differences were found in the distribution of genotypes and alleles between the BPH + HP patients (FF: 27% [21/79], Ff: 30% [24/79], ff: 43% [34/79]) and the controls (FF: 33% [27/81], Ff: 36% [29/81], ff: 31% [25/81]), with statistical significance in the distribution of the genotype ff (P < 0.05). The histological prostatitis group showed a significant difference from the controls in the frequency of the f allele (58% [196/338] vs 49% [153/312], P < 0.05), but not in that of the F allele (42% [142/338] vs 51% [159/312] , P > 0.05). CONCLUSION: VDR Fok I polymorphisms may be correlated with BPH complicated by histological prostatitis. PMID- 22049789 TI - [Effects of staurosporine on the proliferation and apoptosis of prostate cancer PC-3 cells]. AB - OBJECTIVE: To investigate the effects of staurosporine (ST) on the proliferation and apoptosis of prostate cancer PC-3 cells. METHODS: Prostate cancer PC-3 cells were treated in vitro with ST at 10(-8) mol/L. The expressions of cyclin A and cyclin D1 proteins in the cells were detected by Western blot, the effect of ST on the proliferation of the cells determined by MTT assay and plate colony formation, the apoptosis of the cells examined by flow cytometry, and their morphological changes observed under the light microscope. RESULTS: ST treatment markedly decreased the expressions of cyclin A and cyclin D1 in the PC-3 cells, and significantly inhibited the growth of the PC-3 cells (19.35%) at 48 h. (F = 31.06, P < 0.01). The colony formation rate of the PC-3 cells was (37.10 +/- 3.43) % in the ST group, significantly lower than (64.80 +/- 4.34) % in the control (chi2 = 14.59, P < 0.05) and (62.80 +/- 4.36) % in the DMSO group (chi2 = 12.50, P < 0.05), while the apoptosis rate of the cells was remarkably higher in the ST group ([19.6 +/- 2.20] %) than in the control ([5.33 +/- 1.40] %) and the DMSO group ([5.50 +/- 0.96] %) (F = 104.36, P < 0.01). Under the light microscope, the ST-treated cells were round with indistinct margins as compared with those of the other two groups. CONCLUSION: ST could significantly inhibit the proliferation and induce the apoptosis of PC-3 cells. PMID- 22049790 TI - [Expressions of CD4+ CD25(high) regulatory T cells, TGF-beta 1 and COX-2 in the peripheral blood of prostate cancer patients]. AB - OBJECTIVE: To investigate the expressions of CD4+ CD25(high) regulatory T cells, TGF-beta 1 and COX-2 in the peripheral blood of prostate cancer (PCa) patients, and analyze the role of CD4+ CD25(high) regulatory T cells in the pathogenesis of PCa and their relationship with TGF-beta 1 and COX-2. METHODS: We used flow cytometry to calculate the percentage of CD4+ CD25(high) regulatory T cells in the CD4+ T cells in the peripheral blood mononuclear cells (PBMC) from 30 PCa patients (11 localized and 19 non-localized cases) and 20 healthy volunteer controls, determined the expressions of TGF-beta 1 and COX-2 in the serum by ELISA, and analyzed their correlation with the CD4+ CD25(high) regulatory T cells in the PCa patients as well as the differences between the localized and non- localized cases. RESULTS: CD4+ CD25(high) regulatory T cells accounted for (18.32 +/- 7.49) % in the CD4+ T cells in PBMCs from the PCa patients, significantly higher than (7.77 +/- 1.86) % from the controls (P < 0.05), but with no statistically significant difference between pre- and post-treatment in the PCa patients (P > 0.05). The expressions of TGF-beta 1 and COX-2 in the peripheral blood were (215.97 +/- 55.16) ng/ml and (6.88 +/- 5.14) ng/ml in the PCa patients, in comparison with (149.75 +/- 47.11) ng/ml (P < 0.05) and (6.88 +/- 5.14) ng/ml (P > 0.05) in the controls. Multiple linear regression analysis showed no significant correlation between the expression of CD4+ CD25(high) regulatory T cells in PBMCs and those of TGF-beta 1 and COX-2 in the peripheral blood of the PCa patients. There were no significant differences between the localized and non-localized PCa groups in the expressions of CD4+ CD25(high) regulatory T cells, TGF-beta 1 and COX-2 (P > 0.05). CONCLUSION: CD4+ CD25(high) regulatory T cells in in PBMCs are involved in the pathogenesis of PCa. The proliferation of CD4+ CD25(high) regulatory T cells is not significantly correlated to the expressions of TGF-beta 1 and COX-2 in the peripheral blood, but maybe to the tumor itself and the local tumor microenvironment. PMID- 22049791 TI - [Tadalafil for ED after transurethral resection of the prostate: a report of 113 cases]. AB - OBJECTIVE: To evaluate the efficacy of tadalafil in the treatment of ED after transurethral resection of the prostate (TURP). METHODS: A total of 113 patients with ED after TURP received 3 months of tadalafil treatment and were followed up for 6 months. The IIEF-5 scores of the patients and the number of successful penile intromissions and sustained penile erections in the patients' sexual life diary were compared before and after the treatment. RESULTS: The IIEF-5 scores were 9.83 +/- 3.96 before the medication, 20.23 +/- 3.25 after it, and 17.28 +/- 3.03 at 6 months after drug withdrawal, with statistically significant differences between pre- and post-treatment (P < 0.05). The patients' success rates of penile intromission and sexual intercourse were increased from 44.8% and 7.5% before the medication to 81.7% and 63.2% after it. CONCLUSION: Tadalafil can be used as a first-line drug for the treatment of ED after TURP. PMID- 22049792 TI - [High ligation of the spermatic vein and sperm DNA fragmentation]. AB - OBJECTIVE: To investigate the effect of high ligation of the spermatic vein (HLSV) on DNA fragmentation in varicocele (VC) patients. METHODS: Thirty-four VC patients underwent HLSV. Sperm motion indexes and the results of papanicolaou staining and DNA fragmentation detection were analyzed before and 3 months after the operation according to the WHO guidelines. RESULTS: Compared with pre operation, HLSV achieved a significant increase in the percentage of morphologically normal sperm (P < 0.01), and remarkable decreases in DNA fragmentation, sperm deformity index (SDI) and multiple anomalies index (MAI) (P < 0.01). The patients also showed significant increases in sperm concentration and the percentages of grade b sperm (P < 0.05) and grade a and a + b sperm (P < 0.01) after the operation. The post-operative percentages of sperm DNA fragmentation in those with grades I - III VC were markedly lower (P < 0.01), but showed no significant difference from that in those with subclinical VC (P > 0.05). The percentage of big-halo sperm was significantly increased (P < 0.01), while those of the medium-, small- and non-halo sperm remarkably decreased (P < 0.01) after HLSV. CONCLUSION: HLSV can effectively improve the sperm quality of VC patients. PMID- 22049793 TI - [A combined method for weighing human semen volume]. AB - OBJECTIVE: To search for a method for the precise measurement of human semen volume so as to provide reliable evidence for clinical semen analysis. METHODS: The volumes of 492 semen samples collected from 137 donors by Zhejiang Human Sperm Bank were measured respectively by three different methods including electronic balance weighing, volumetric cylinder measuring, and combination of the two methods above. With the combined measuring method, the semen weight was first obtained by electronic balance weighing, then the semen density determined by volumetric cylinder measuring, and lastly the semen volume figured out by a formula. Paired sample t-test was used to compared the combined method with electronic balance weighing and volumetric cylinder measuring. RESULTS: The mean volume of the 492 semen samples obtained by the combined measuring method was (3.46 +/- 1.17) ml, significantly lower than (3.75 +/- 1.21) ml from electronic balance weighing (P < 0.05) and markedly higher than (3.22 +/- 1.16) ml from volumetric cylinder measuring (P < 0.05). The mean semen density of the 492 samples was (1.0928 +/- 0.0761) g/ml, and the mean weight of the residual semen in the container used in volumetric cylinder measuring was (0.269 +/- 0.122) g. CONCLUSION: Semen volume measured by electronic balance weighing is higher while that obtained from volumetric cylinder measuring is lower than the actual value. An accurate semen volume can be achieved by the combined measuring method, which, therefore, deserves to be widely used both clinically and in researches. PMID- 22049794 TI - [Modified urethral pull-through procedure for posterior urethral stricture or atresia]. AB - OBJECTIVE: To evaluate the feasibility and safety of the modified urethral pull through procedure for the treatment of posterior urethral stricture or atresia. METHODS: We retrospectively analyzed 212 cases of posterior urethral stricture or atresia treated by the modified urethral pull-through procedure. The length of the stricture or atresia was 1.5 - 12 cm, and 66 cases had experienced 1 - 4 previous unsuccessful urethral repairs. Simple transperineal approach was adopted in 208 cases and transperineal-inferiorpubic approach in the other 4. And 15 of the patients underwent urethral construction with grafts. RESULTS: Satisfactory voiding was achieved in 198 (93.4%) of the patients, of whom 16 received 3 - 15 urethral dilations. Of the 14 cases that failed, 10 succeeded after a second and 2 after a third operation. Of the 15 cases that underwent substitution urethroplasty, 14 achieved satisfactory voiding, and only 1 needed repeat dilation. No serious complications were observed in any of the patients. CONCLUSION: Modified urethral pull-through procedure, with its advantages of safety, mini-invasiveness, simple operation and high success rate, is feasible for the treatment of posterior urethral stricture or atresia, while for that with the length >5 cm, substitution urethroplasty should be considered. PMID- 22049795 TI - [Expressions of integrinalpha2beta1 and CD133 in benign prostatic hyperplasia complicated by prostatitis and their significance]. AB - OBJECTIVE: To study the expressions of Integrinalpha2beta1 and CD133 in benign prostatic hyperplasia (BPH) complicated by prostatitis and their significance. METHODS: Specimens were obtained from 56 BPH patients undergoing transvesical prostatectomy. Paraffin sections of the specimens were subjected to HE staining for pathological examination of inflammatory changes under the light microscope. Twenty-four patients with simple BPH were included in Group A, and the other 32 with BPH complicated with prostatitis in Group B. The expressions of Integrinalpha2beta1 and CD133 in the prostatic tissues of the two groups were determined by immunohistochemistry, Western blotting and IPP6.0 image analysis software. RESULTS: The expressions of Integrinalpha2beta1 and CD133 were significantly higher in Group B than in A (P < 0.05), and so were the mean relative value of the optical density of Integrinalpha2beta1 (0.29 +/- 0.18 vs 0.04 +/- 0.03) and that of CD133 (0.08 +/- 0.07 vs 0.0020 +/- 0.0018) (P < 0.05). CONCLUSION: Inflammation can up-regulate the expressions of Integrinalpha2beta1 and CD133 in BPH tissue. PMID- 22049796 TI - [Calcitonin gene-related peptide induces phenotypic transformation of corpus cavernosum smooth muscle cells in diabetic rats with erectile dysfunction]. AB - OBJECTIVE: To explore the effect of the calcitonin gene related peptide (CGRP) on the phenotypic transformation of corpus cavernosum smooth muscle cells (CCSM) in diabetic rats with erectile dysfunction (ED). METHODS: Models of diabetes and diabetic ED were established in male Sprague-Dawley rats by administration of streptozotocin, and CCSMs were primarily cultured and subjected to immunocytochemical assay. The cells were divided into a diabetic ED and a normal control group, and exposed to 0, 10, 60 and 100 nmol/L of CGRP for 24 hours. Then the relative expressions of calponin 1 (Cnn1) and osteopontin (OPN) mRNA were determined by real-time fluorescence quantitative RT-PCR (qRT-PCR). RESULTS: The rate of SMalpha-actin positive cells in the CCSMs was (95.94 +/- 0.03) %. The expression of Cnn1 mRNA was significantly lower while that of OPN mRNA remarkably higher in the diabetic ED rats (4.41 +/- 0.29 and 5.28 +/- 0.32) than in the normal controls (10.35 +/- 0.62 and 1.32 +/- 0.24) (P < 0.01). Exposure to 100 nmol/L of CGRP significantly upregulated the expression of Cnn1 mRNA and downregulated that of OPN mRNA as compared with the unexposed rats (6.9 +/- 0.22 vs 4.41 +/- 0.29 and 3.26 +/- 0.31 vs 5.28 +/- 0.32, P < 0.01). CONCLUSION: CGRP can transform the phenotype of CCSMs in diabetic ED rats from contractile to synthetic type. PMID- 22049797 TI - [Undifferentiated prostate sarcoma with cartilage metaplasia: a case report and review of the literature]. AB - OBJECTIVE: To investigate the clinical presentations and pathologic features of undifferentiated sarcoma of the prostate with cartilage metaplasia, and to clarify its category. METHODS: We analyzed the clinical data of a case of undifferentiated sarcoma of the prostate with cartilage metaplasia treated by surgical resection. The tumor tissue was subjected to routine HE and immunohistochemical staining, its histological structure and immunohistochemical expression were observed under the light microscope, and relevant literature on its manifestations was reviewed. RESULTS: The case was pathologically diagnosed as gray prostate tumor, with chondrosarcomatous and undifferentiated malignant mesenchymal components under the light microscope. Immunohistochemical staining revealed vimentin (+), local CD117 (+/-), SMA (-), Des (-), myoglobin (-), CD34 ( ), CK7 (-), and CK8 (-). Tumor metastasis was found 2 months after the operation, and the patient died 4 months later. CONCLUSION: Undifferentiated sarcoma of the prostate with cartilage metaplasia is a very rare and highly malignant aggressive tumor, which can be diagnosed by biopsy and immunohistochemistry. PMID- 22049798 TI - [Oral paroxetine for premature ejaculation: a randomized controlled study]. AB - OBJECTIVE: To validate the therapeutic efficacy of paroxetine in the treatment of premature ejaculation (PE). METHODS: Eighty PE patients up to the inclusion criteria were equally randomized to an experimental and a control group. We observed all the patients for 4 weeks and recorded the baseline data on intravaginal ejaculatory latency time (IELT) and sexual satisfaction scores, followed by oral medication of paroxetine at 20 mg/d for the patients in the experimental group and placebo for the controls. Thirty days after the treatment, we again recorded IELT and sexual satisfaction scores of the patients. RESULTS: After the treatment, the experimental group showed significantly prolonged IELT ([5.75 +/- 1.24] min) and increased sexual satisfaction score (6.4 +/- 1.2) as compared with the baseline data ([0.89 +/- 0.21] min and [2.7 +/- 0.9]) (P < 0.01). The control group exhibited no significant differences before and after the medication either in the mean IELT or in sexual satisfaction scores ([1.06 +/ 0.28] min vs [0.97 +/- 0.18] min and 3.6 +/- 1.3 vs 3.1 +/- 1.1, P > 0.05). CONCLUSION: Oral medication of paroxetine at 20 mg/d for 30 days could improve IELT and sexual satisfaction in PE patients. PMID- 22049799 TI - [Effects of remifentanil combined with naloxone on human sperm motility]. AB - OBJECTIVE: To observe the effects of remifentanil combined with naloxone on human sperm motility in vitro and to investigate its possible mechanism. METHODS: Twenty normal semen samples were collected, each divided into 13 aliquots, one as the control and the others treated in vitro with different concentrations of remifentanil or remifentanil + naloxone for 35 min. The percentage of progressive mobile sperm was assessed by computer-assisted sperm analysis at 5, 10, 15, 20 and 35 min. RESULTS: Compared with the control group, remifentanil at 0.1, 1, 10 and 100 microg/L significantly decreased sperm motility at 5 and 10 min in a dose dependent manner, with no significant difference at 15 and 30 min; sperm motility showed no significant difference on 5 -35 min exposure to naloxone at 0.004 -0.04 mg/L, nor on 5, 10, 15 and 20 min exposure at 0.4 -4 mg/L, but was significantly increased at 35 min. Compared with the corresponding concentrations of remifentanil alone, remifentanil + naloxone remarkably increased sperm motility at 0.1 + 0.004, 1 + 0.04, 10 + 0.4, and 100 + 4 mg/L at 5 and 10 min, with no obvious difference at 15 and 30 min. CONCLUSION: The onset and offset of the effect of remifentanil on sperm motility are rapid and its inhibitory effect can be antagonized by naloxone, which may be related with the micro-opioid receptor. PMID- 22049800 TI - [Progress in the treatment of penile defect]. AB - As the important external genitalia of males, penis has the functions of both urination and copulation. Battle wound, other trauma, and some diseases such as penile cancer can result in total and partial penile defect, which has great impact on the sufferers' mind and life. Therefore, the treatment of penile defect is receiving more and more importance from both the patients and doctors. The ideal treatment is expected to achieve a satisfactory appearance, unobstructed standing urination and successful copulation. Nowadays, the main clinical techniques for the treatment of penile defect include penile replantation, penile lengthening, and penile reconstruction. The progress made in transplantation immunity, tissue matching, immunosuppressive agents, and long-term surviving of animal allograft limb transplantation has prepared a firm ground for human penile allograft. The construction of penile tissues by tissue engineering techniques is still at the experimental stage. It would be a valuable research how to assimilate the constructed and autologous tissues in clinical practice so as to achieve better function and appearance of the penis. PMID- 22049801 TI - [Molecular genetics of globozoospermia: an update]. AB - Globozoospermia, as a severe teratozoospermia caused by gene mutations, is a rare congenital disease with main clinical manifestations of the round head of sperm and abnormality or absence of acrosome, and its precise mechanism is not yet clear. Studies show that the pathogenic genes associated with globozoospermia include SPATA16, PICK1, GOPC, Hrb, Csnk2a2 and bs. This paper outlines the progress in the studies of molecular genetics of globozoospermia, aiming to contribute to the molecular diagnosis and mechanism investigation of the disease. PMID- 22049802 TI - [Chronic prostatitis and cytokines]. AB - Chronic prostatitis (CP) is a common disease in men, and its pathogenesis remains to be clarified. The precise regulation of cytokines is involved in all types and all stages of CP. The interaction of inflammation, inflammatory cells and cytokines leads to the development and progression of CP. With further understanding of the immunological and molecular biological mechanisms of the disease and more inflammatory cytokines used in its detection, it is of special significance to apply cytokines in the classification and treatment of CP. This review outlines the roles of cytokines in the pathogenesis of CP, particularly chronic pelvic pain syndrome (CPPS), their relationship with CP, and their significance in the classification and diagnosis of CP/CPPS. PMID- 22049803 TI - [Impact of endocrine disrupting chemicals on semen quality]. AB - Endocrine disrupting chemicals (EDCs) are natural or man-made agents that interfere in some way with human or animal normal endocrine function, and even influence the endocrine function of their offspring. There are many kinds of EDCs, which are widely present in soil, water, and even food. This review elaborates the impact of EDCs on human and animal semen quality from the viewpoint of epidemiology and biology by focusing on pesticides, plasticizers and detergents. PMID- 22049805 TI - Difficult decisions. PMID- 22049804 TI - [Compound Xuanju capsule improves sex hormones and sex organ indexes in castrated male rats]. AB - OBJECTIVE: To investigate the effects of Compound Xuanju Capsule on the levels of sex hormones and the weight of sexual organs in castrated male rats. METHODS: A randomized model control trail was performed in 60 young male SD rats of SPF grade, of which 12 were included in the normal control group, and the others were castrated and randomly divided into a model control group and a high-dose, a median-dose and a low-dose Xuanju group. The control groups received intragastric administration of normal saline, and the model groups solution of Compound Xuanju Capsule, all for 20 days. Then we determined by radioimmunoassay the levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the peripheral blood of the rats, and measured the weights of the epididymis, preputial gland, seminal vesicle, prostate and levator ani muscle. RESULTS: The T levels were remarkably lower in the castrated groups than in the normal controls, and significantly higher in the three Xuanju groups than in the model controls (P < 0.01). Both LH and FSH levels were increased in the model control and Xuanju groups as compared with the normal control group, the former with statistically significant difference (P < 0.05) and the latter without. In comparison with the normal controls, the model control rats showed a marked reduction in the indexes of the preputial gland, seminal vesicle, prostate and levator ani muscle, and the high-dose Xuanju group exhibited a significant increase in the seminal vesicle index as compared with the model controls (P < 0.05). There were no statistically significant differences in the indexes of preputial gland, prostate and levator ani muscle among different dose groups (P > 0.05). CONCLUSION: Compound Xuanju Capsule can elevate T and LH levels in the peripheral blood of male SD rats and improve the indexes of their sex organs, which may be an important mechanism behind its effect on ED. PMID- 22049806 TI - Preparation of the resuscitation room and patient reception. AB - Experience from the Role 3 Medical Treatment Facility in Afghanistan has allowed the development of a variety of processes to improve management of seriously injured patients. This review describes some of the techniques that facilitate the reception of the patient in the Emergency Department. In particular the preparation of the team and the resuscitation bay, and the way the team members work together to optimise assessment and resuscitation while minimising delay to imaging and surgery. Within this context the systems described have been refined and function effectively. Many of these lessons may be relevant to future deployments. PMID- 22049807 TI - Critical decision-making and timelines in the emergency department. AB - The resuscitation of severely injured patients has evolved during the last decade. Patients are now surviving injuries that previously were thought to be unsurvivable. Systems have been put in place, that reflect the intensity of workload and severity of injury of patients presenting to deployed medical treatment facilities. This paper aims to describe some of the elements that may differ from routine practice in the resuscitation room, and in particular the role of timelines in the management of such patients. PMID- 22049808 TI - Massive transfusion. AB - Massive Transfusion is a part of Damage Control Resuscitation. The aim of transfusion therapy is to restore oxygen delivery to poorly perfused tissues and to treat the acute coagulopathy of trauma. The severity and complexity of modern injuries have led to the use of swift, protocol-driven care with the use of'Shock Packs' and management of metabolic complications. The proactive treatment of the coagulopathy has been termed Haemostatic Resuscitation. The delivery of this transfusion capability has required an increasingly sophisticated logistic and laboratory response. New operational capabilities have included cold chain solutions; laboratory management information systems; platelet apheresis and ROTEM. This investment in the massive transfusion capability has delivered rapid resuscitation. It has also enabled clinicians to direct individualised transfusion support following initial resuscitation i.e. goal directed therapy. Future technical solutions should further support the prehospital delivery of transfusion while addressing the logistic tail. However, the key to success is the knowledge and skills of frontline staff to deliver safe and appropriate blood transfusion. PMID- 22049809 TI - Major military trauma: decision making in the ICU. AB - The management of trauma in the field intensive care unit has evolved in recent years. Key issues in current practice and organisation are discussed, with particular attention to areas where civilian and military practice differs. Possible future improvements are explored. PMID- 22049810 TI - Use of imaging in trauma decision-making. AB - Damage Control Radiology describes the process where imaging aids the decision making process in a trauma setting and is an important part of Damage Control Surgery and Resuscitation. This article outlines how radiology fits in to the primary and secondary surveys and discusses the role of imaging modalities such as ultrasound and CT. The importance of deployed radiology to aid rapid diagnosis and decision making is described. PMID- 22049811 TI - Making difficult decisions in major military trauma: a crew resource management perspective. AB - The purpose of this article is to consider three underappreciated but important features of high performance teams: the trade-off relation between social and technical competence, the relevance of team size on productivity, and the inevitability of tensions that, while often experienced as dysfunctional, are in fact quite useful. It does so by reviewing a series of related studies in aviation and the organisation sciences, and by extrapolating insights for crew resource management in major military trauma along two generic themes: team context and team process. PMID- 22049812 TI - Current controversies in military pre-hospital critical care. PMID- 22049813 TI - Right turn resuscitation: frequently asked questions. AB - In this article the process of operating room resuscitation - commonly known as Right Turn Resuscitation (RTR) when conducted in the medical treatment facility at Camp Bastion - is described. The place of RTR within the concepts of damage control resuscitation and surgery is discussed along with activation criteria and protocols. The medical leadership, team roles, advantages and disadvantages are reviewed. Finally, studies describing the impact of RTR and operating room resuscitation are briefly described. PMID- 22049814 TI - Limb salvage of severely injured extremities after military wounds. AB - Severely wounded extremities following battlefield injuries present a surgical dilemma to military surgeons of whether to attempt salvage or amputate the limb. There are many considerations to be made, including local and systemic patient factors, other wounded personnel and logistical constraints. Attempts have been made previously to form objective scoring criteria so as to remove possible subjectivity in this decision-making process. Furthermore, paediatric patients present their own particular dilemmas. This paper examines these various matters and, with contemporaneous evidence, presents recommendations for management. PMID- 22049815 TI - Difficult decisions in the surgical care of military casualties with major torso trauma. AB - Testing and difficult decision-making is a sine qua non of surgical practice on military operations. Better pre-hospital care protocols, reduced evacuation timelines and increased scrutiny of outcome have rightfully emphasised the requirement of surgeons to "get it right, first time and every time" when treating patients. This article addresses five contentious areas concerning severe torso trauma, with relevant literature summarised by a subject matter expert, in order to produce practical guidance that will assist the newly deployed surgeon in delivering optimal clinical outcomes. PMID- 22049816 TI - Paediatric trauma management on deployment. AB - There remains a significant paediatric workload through the military hospital in Camp Bastion. In this paper the authors review and discuss particular problems with resuscitation, investigation, anaesthetic and surgical issues in dealing with children suffering from ballistic injuries. Personal experience and recent papers are used for a qualitative analysis of difficult decisions in the management of paediatric ballistic trauma. Key questions are answered in separate paragraphs for each specialty. The information described in this paper should assist any deployed physician deal with paediatric casualties particularly if they are unaccustomed to paediatric patients in their normal practice. PMID- 22049817 TI - Nutritional management of critically ill trauma patients in the deployed military setting. AB - The role of nutritional support in critical illness is well established. This article reviews the nutritional management of military trauma patients in the deployed setting, which poses special challenges for the surgeon and intensivist. There is little direct evidence relating to the nutritional management of trauma patients in general, and military trauma patients in particular, but much of the evidence accrued in the civilian and non-trauma critical care setting can be extrapolated to military practice. There is strong consensus that feeding should be commenced as soon possible after injury. Enteral nutrition should be used in preference to parenteral nutrition whenever possible. If available, supplemental parenteral feeding can be considered if enteral delivery is insufficient. Gastrointestinal anastomoses and repairs, including those in the upper gastrointestinal tract, are not a contraindication to early enteral feeding. Intragastric delivery is more physiological and usually more convenient than postpyloric feeding, and thus the preferred route for the initiation of nutritional support. Feeding gastrostomies or jejunostomies should not be used for short-term nutritional support. Enteral feeding of patients with an open abdomen does not delay closure and may reduce the incidence of pneumonia, and enteral nutrition should be continued for scheduled relook surgery not involving hollow viscera or airway. Glutamine supplementation may improve outcome in trauma patients, but fish-oil containing feeds, while showing some promise, should be reserved for subgroups of patients with ARDS. PMID- 22049818 TI - The deployed medical director: managing the challenges of a complex trauma system. AB - Contemporary combat casualty care has never been more sophisticated or effective, which is matched by an unprecedented level of clinical complexity. The management of this complexity has demanded the evolution of a more direct clinical leadership model in the field hospital: the Deployed Medical Director (DMD). The DMD has a central co-ordinating role in reducing the friction generated by individuals' unfamiliarity in a rapidly developing clinical environment that has diverged from the NHS; in cementing interoperability within a multinational medical treatment facility working at high intensity; and in maintaining and developing the highest clinical standards within the deployed trauma system. This article describes the evolution of the DMD role and illustrates the challenges through a series of vignettes. Particular emphasis is given to the organisational risk that the role carries through necessary ethical choices, the requirement to integrate multi-national cultural differences and the challenge of dealing with interpersonal frictions amongst senior staff. PMID- 22049819 TI - Emphasizing qualitative study. PMID- 22049820 TI - Time for an undergraduate curriculum in general practice for Nepal. AB - INTRODUCTION: This is a qualitative study, to generate a framework for a core curriculum in General Practice in the undergraduate setting, designed specifically for Nepal. METHODS: A Delphi process was used to involve representatives from the GP faculty in Institute of Medicine, BP Koirala institute BPKIHS, Patan Hospital/National Academy Medical Sciences and Tansen mission hospital. The Delphi involves getting input from an identified group of experts and progressively feeding back the results from each round of enquiry so that subsequent views are influenced until a point of convergence is reached. In effect the Delphi not only analyses problems and identifies solutions, but can begin the process of commitment to change. RESULTS: A prioritized list of the key outcomes for an undergraduate GP curriculum was developed and a broad list of knowledge, skills and attitudes were defined. A balance was observed between the need to train doctors who are skilled in communication, who have compassion for their patients, who are also required to be excellent rational clinicians able to respond to emergency situations. There was also the need for doctors to be competent not just in individual clinical care, but in the care of communities. CONCLUSIONS: General Practice, as a core component of primary care, should be an obligatory part of every undergraduate medical curriculum. This Delphi process has produced an important framework for a national undergraduate curriculum in General Practice, designed specifically for Nepal. PMID- 22049821 TI - Early experience of day care surgery in Nepal. AB - INTRODUCTION: The day care laparoscopic cholecystectomy (DCLC) is found to be safe and effective in developed countries. However, it has not been well accepted in our part of the world probably because of lack of infrastructures,established norms and published reports. We have analyzed the safety and feasibility of the procedure in the recently established first dedicated day care surgery centre of the country. METHODS: All the patients with American society of anaesthesiologist (ASA) score I and II admitted for laparoscopic cholecystectomy are included. Operation are performed in the morning and closely observed till evening. Patients found to be medically fit to discharge; having a responsible person at home and who can make their own arrangements in case of problems were advised for discharge. Follow up was done by telephone call from next morning. RESULTS: Total 35 patients underwent laparoscopic cholecystectomy. Age range was between 16-65 years and most of them were females (88%). Only 30 patients were operated in early morning and were eligible for day care surgery. 25 (83%) Patients were advised for discharge but only 10 (33%) could make arrangement. Other 15 patients could not go home mainly due to different psychosocial reasons. Only one patient needed readmission and Complications observed were minor and relatively few. CONCLUSIONS: Day care laparoscopic cholecystectomy is safe and feasible in our set up. Acceptance of the procedure is expected to increase once it is regularly practiced and awareness in improved. PMID- 22049822 TI - Anaesthesia and perioperative care in remote health camps: patients' concerns. AB - INTRODUCTION: Identifying patients' concerns and expectations regarding anaesthesia and perioperative care in mobile surgical camps is relevant for the camp workers. This prospective observational study was conducted to assess knowledge, concerns, and expectations about anaesthesia and perioperative care in patients undergoing surgery in mobile surgical camps in remote mountainous districts of Eastern Nepal. METHODS: A questionnaire with seven items related to anaesthesia and perioperative care was used for interviewing 80 individuals of age > or = 12 years, 20 from each camp at Solukhumbu, Sankhuwasabha, Khotang and Bhojpur districts. RESULTS: Data of two patients were lost leaving only 78 individuals for analysis. The mean age of the subjects was 30.5 (+/- 14.6) years with the male: female ratio of 43: 35. Fifty-eight (74.4%) patients had some gross idea about the modality of administration of anaesthetics. Twenty-six (33.3%) individuals preferred GA over local anaesthesia, whereas 22 (28.2%) were happy either way if there was no pain. Pain was the main concern for 73.1% of the patients. Of the 25 patients expressing fear of GA, death or not being able to wake up anymore was the main concern for 60.0%. Increasing age was associated with lower fear of GA (p < 0.05). Surgical experience was distressing for 17 (21.8%) patients. The overall experience of the anaesthesia and surgery was worse than expected for 25.6% of the patients. CONCLUSIONS: Patients presenting to these health camps have limited knowledge regarding anaesthesia and perioperative care but have valid concerns and expectations in respect of their safety, comfort and outcome. PMID- 22049823 TI - T-tube vs primary common bile duct closure. AB - INTRODUCTION: Closure of the common bile duct over T-tube after exploration is a widely practiced traditional method. However, its use may give rise to many complications. We do primary closure of common bile duct after exploration. Aim of the study is to see the efficacy and safety of the primary closure. METHODS: Study was carried out to compare the results of both the techniques from 2006 to 2009 in the cases proven to have common bile duct stone with or without the features of obstructive jaundice. Post operative hospital stay and morbidities related to both the groups were recorded and analyzed. RESULTS: There were total 71 cases included in the study. Thirty one in T-tube group and 40 in primary closure group. T-tube was removed in most of the cases after three weeks where as average time of drain removal in primary closure group is 5.79 +/-1.79 days. Incidence of retained stone was equal in each group. Major complication in T-tube group is biliary peritonitis in four patients at the time of T-tube removal whereas none of the patient from primary closure group suffered from such major complication. CONCLUSIONS: Primary closure after the common bile duct exploration is safe and it helps to avoid the morbidities related to T-tube. PMID- 22049824 TI - Need of improvement in timing of prophylactic antibiotic in elective surgery. AB - INTRODUCTION: Infections in surgery are major concern of morbidity, mortality, and costs. Timely antibiotic prophylaxis before incision ensures optimum concentration of AP in blood and tissues to prevent surgical site infections . However, proper timing of AP remains problematic as reported by various studies, though none so far from Nepal. Aim of this prospective observational study was to assess and address the issues for improvements in timing of AP. METHODS: The pattern of antibiotic prophylaxis were prospectively collected in respect to time of induction, and incision time were recorded on predesigned 'AP form'. The study included all the elective major cases who received AP of intravenous Cefazoline 1 g as per our existing protocol. The emergency surgeries and obstetric cases were excluded from the study. RESULTS: There were 125 cases of which 89% received AP before incision (63% within 5 minutes before incision), while 11% had AP after the incision and 1% within the recommended time period of 2 hour to 30 minutes before incision. CONCLUSIONS: Current practice of antibiotic prophylaxis (AP) needs improvement as per standard guidelines of AP within 2 hour to 30 before incision. PMID- 22049825 TI - Nurses' views on need for professional development in Nepal. AB - INTRODUCTION: This study explores the nurses' views on need for professional development and barriers in Nepal. METHODS: This is a qualitative content analysis study conducted among nurses from different health institutes. In-depth interviews and focus group discussions were used to obtain their views on need of professional development and major barriers against professional development in Nepal. Eleven nurses for in-depth interviews and three groups of six nurses each for focus group discussions were selected purposefully from Kathmandu University Hospital, Dhulikhel and Tribhuban University Teachng Hospital, Kathmnadu. RESULTS: Five themes emerged from qualitative data. "Continuing professional development", "supportive management", "nursing leadership", "recognition and respect" and "professional networking" were considered as essential factors for professional development. Lack of "commitment by the nurses", "female gender professional" and "lack of autonomy" were felt as barriers for the nursing professioanl development. CONCLUSIONS: Continuing professional development and supportive working environment are crucial to make nursing profession more dynamic and appealing in Nepal. PMID- 22049826 TI - Single incision laparoscopic cholecystectomy vs conventional cholecystectomy in developing country. AB - INTRODUCTION: Use of laparoscopic surgery has demanded principles of less trauma of access hence less scar and so probably less complications. Hence conventional laparoscopic surgeries were tried with natural orifice transluminal surgery (NOTES) and then single incision laparoscopic surgery (SILS). With refinement in instruments and surgeons skills SILS have bridged up between conventional and NOTES in order to quench the desire of less or no scar at all. METHODS: Comparative case control study between conventional laparoscopic cholecystectomy and SILS in public teaching hospital. RESULTS: Total 20 patients underwent SILS cholecystectomy and 20 underwent conventional cholecystectomy and found that no difference between both in terms of post operative pain score, hospital stay and post operative wound infection except significant difference in mean operative time and patient's level of satisfaction was less in patient with SILC if were subjected to pay for instruments in order to maintain cosmesis. CONCLUSIONS: Though SILS have gained rapid acceptance in surgical fraternity, large number of randomized controlled trials are necessary to show its benefit over conventional laparoscopic cholecystectomy. PMID- 22049827 TI - Antimicrobial resistant Streptococcus pneumoniae. AB - INTRODUCTION: Pneumococcal infections are important cause of morbidity and mortality. Knowledge of antimicrobial susceptibility patterns plays important role in the selection of appropriate therapy. Present study was undertaken to analyze the susceptibility patterns of pneumococcal isolates against commonly used antimicrobials with special reference to determination of minimum inhibitory concentration (MIC) of penicillin in a tertiary care hospital in eastern Nepal. METHODS: Twenty-six strains of S. pneumoniae isolated from various clinical specimens submitted to microbiology laboratory were evaluated. All isolates were tested for antimicrobial susceptibility by disk diffusion method. MIC of penicillin was tested by broth dilution method. RESULTS: Of the total isolates 19 (73%) were from invasive infections. Seven isolates were resistant to cotrimoxazole. No resistance to penicillin was seen in disk diffusion testing. Less susceptibility to penicillin (MIC 0.1-1.0 mg/L) was observed in five (17%) isolates. High level resistance to penicillin was not detected. One isolate was multidrug resistant. CONCLUSIONS: S. pneumoniae isolates with intermediate resistance to penicillin prevail in Tertiary Care Hospital in eastern Nepal, causing invasive and noninvasive infections. As intermediate resistance is not detected in routine susceptibility testing, determination of MIC is important. It helps not only in the effective management of life threatening infections but is also essential in continuous monitoring and early detection of resistance. In addition, further study on pneumococcal infections, its antimicrobial resistance profile and correlation with clinical and epidemiological features including serotypes and group prevalence is recommended in future. PMID- 22049828 TI - In-vitro activity of three brands of ceftriaxone against different clinical isolates. AB - INTRODUCTION: Ceftriaxone is an extended spectrum cephalosporin that has been used for decades for combating infections caused by wide array of pathogens and prescription of antibiotic is in favor of specific brands without realizing the potency of the brand. The in-vitro activity of three brands of ceftriaxone and various antibiotics against clinical isolates is studied. METHODS: This comparative study was carried in Kathmandu Medical College Teaching Hospital (KMCTH), Basic Science Complex, Duwakot, Bhaktapur in 2009. Thirteen clinical isolates isolated from the specimens processed in the Microbiology Laboratory at KMCTH were used. Minimum inhibitory concentration (MIC) of three brands of ceftriaxone (A, B, and C) was determined by agar dilution and antibiotic resistance patterns were deduced by disc diffusion test. RESULTS: MIC for three brands of ceftriaxone ranged from < 0.25 to > 256 mg/L. The MIC for brands A and C of ceftriaxone were consistent for all isolates while for brand B, MIC was higher by at least two fold suggesting this brand had less in-vitro activity against isolates tested. All isolates were multi-drug resistant. Ceftriaxone resistant isolates (n = 6) were simultaneously resistant to various antibiotics tested. Imipenem and amino glycosides were sensitive to the isolates studied. CONCLUSIONS: Different brands of ceftriaxone are available in Nepal and imprudent use of less potent antibiotics should be controlled to stop the emergence and spread of multi-drug resistant pathogens and to prevent undue economic burden to the patient and the country. PMID- 22049829 TI - Fracture union in closed interlocking nail in femoral fracture. AB - INTRODUCTION: Fractures shaft femur is a major cause of morbidity and mortality in patients with lower extremity injuries. The objective of this study was to find out the outcome of Interlocking nail in fracture femur. METHODS: This study was conducted in the Department of Orthopaedic surgery in M. M. Medical College from July 2006 to November 2008. Seventy eight patients were recruited from Emergency and out patient department having closed fracture of femoral shaft. All patients were operated under general or spinal anesthesia. All patients were followed for nine months. RESULTS: Out of seventy eight patients, sixty nine patients underwent union in 90 to 150 days with a mean of 110.68 days. Touch down weight bearing was started on 2nd post-operative day. Complications found in four patients who had non-union, and five patients had delayed union which was treated with dynamization and bone graft. The results were excellent in 88.46% and good in 6.41% patients. CONCLUSIONS: We concluded that this technique is advantageous because of early mobilization (early weight bearing), less complication with good results and is economical. PMID- 22049830 TI - Antibiotic susceptibility patterns of Vibrio cholerae isolates. AB - INTRODUCTION: Cholera is one of the most common diarrhoeal diseases in Nepal. Etiological agent of cholera is Vibrio cholerae which removes essential body fluids, salts and vital nutrients, which are necessary for life causing dehydration and malnutrition. Emerging antimicrobial resistant is common. The aim of the present study was to determine the antibiotic susceptibility pattern of cholera patients in Nepal. METHODS: All the laboratory works were conducted in the bacteriology section of National Public Health Laboratory, Teku from March to September 2005. During this period a total of 340 stool samples from diarrhoeal patients were collected and processed according to the standard laboratory methods. Each patient suffering from diarrhoea was directly interviewed for his or her clinical history during sample collection. RESULTS: A total of 340 stool samples were processed and studied from both sex including all ages of patients. Among the processed sample 53 Vibrio cholerae cases were found. All isolated Vibrio cholerae O1 were El Tor, Inaba. All isolated (100%) Vibrio cholerae O1 were sensitive to Ampicillin, Ciprofloxacin, Erythromycin and Tetracycline whereas all were resistant to Nalidixic acid and Cotrimoxazole. Only 15.1% cases were sensitive to Furazolidone whereas 84.9% were resistant. CONCLUSION: All V. cholerae strains isolated in this study were found resistant to Multi Drug Resistant (resistant to at least two antibiotics of different group). Ampicillin, Ciprofloxacin, Erythromycin and Tetracycline were found still more potent antibiotics against Vibrio cholerae isolated during the study. PMID- 22049831 TI - Giant cell tumor arising from anterior arc of first rib: a rare presentation. AB - We report a case of Giant Cell Tumor (GCT) arising from anterior are of first rib along with literature review which was treated with excision of rib through its normal margin along with tumor mass. GCT of rib is rare and if found mostly arises from the posterior aspect. However, GCT should be considered as differential diagnosis when bony mass is present in the anterior are of rib. It poses surgical challenge for excision because of the delicate and vital neurovascular structures passing above it between clavicle and first rib. PMID- 22049832 TI - Self injurious behavior in temporal lobe epilepsy. AB - Self-injurious behavior (SIB) or self-mutilating behavior (SMB) is rare but can occur in temporal lobe epilepsy. Such a behavior during seizures is not usually recalled by patient. Here is a case with self mutilating behavior in left temporal lobe epilepsy, presented because of its rare manifestation and diagnostic dilemma. A 19 year old unmarried Muslim student presented to emergency with SMB, guilty rumination and a persecutory delusion. The patient was intermittently confused about place and time. In subsequent assessments, he was found harboring death wishes and suicidal ideation. He transiently had auditory hallucination and thought broadcasting. He episodically tried to harm himself by severely biting only his left ring finger. It was difficult to influence him during such episodes. EEG revealed left temporal lobe seizure. Diagnosis of 'Epilepsy and Organic Psychosis' was made. The patient responded well to Antiepileptic and Antipsychotic medications. PMID- 22049833 TI - Complete bicornuate uterus with complete longitudinal vaginal septum. AB - Bicornuate Uterus is a type of lateral fusion disorder of the mullerian ducts. According to the American Fertility Society Classification of Mullerian Anomalies, bicornuate uterus is a class IV anomaly. Incidence of this anomaly varies. This may affect a woman's obstetric, as well as her gynecologic outcome. Here we present a 23 year primigravida at 38 weeks and 5 days gestation with footling breech presentation. She was identified, during cesarean section, of having complete bicornuate uterus with complete longitudinal vaginal septum. PMID- 22049834 TI - Prospects of jugular venous pulse assessment. AB - There is no controversy regarding the current clinical method of examination of waveform of jugular vein pulse. However there are limitations of clinical assessment of central venous pressure by jugular vein pressure measurement from the level of sternal angle. There are variations in the reported distances from sternal angle to right atrium as well as to upper limit of JVP. In erect position, anterior end of fourth intercostal space is at about the level of mid right atrium. In patients with visible JVP at neck in erect position, measurement of CVP can be done more accurately directly from the anterior end of fourth intercostal space. For others, the position of mid-right atrium can be marked in lateral chest wall first in erect position at the mid-point of an anteroposterior line from anterior end of fourth intercostal space to back. Subsequently in reclining position, the vertical height of venous pressure can be measured from the horizontal plane of the midpoint marked at lateral chest wall to visible upper limit of JVP. Such measurement can be done in a more reliable way with venous pressure (VP) manometer with its indicator rod at the horizontal plane of mid-right atrium and with its horizontal surface at upper limit of JVP. The venous pressure manometer can also be used to measure relatively less reliable upper limb venous pressure (ULVP), as indicated by the vertical distance at which veins of upper limb collapse, especially when JVP is not visualized due to subnormal CVP as in hypovolemia. PMID- 22049835 TI - Novel swine influenza A/H1N1 and the phase six pandemic. AB - The family Orthomyxoviridae consists of Influenza A virus which is negative sense single stranded virus. The genome of the virus is segmented and possesses a peculiar trait of genetic reassortment. The influenza virus on its envelop consists of the antigenic glycoprotein like haemagglutinin (HA) and neuraminidase (NA). The changes in those glycoprotein components due to antigenic shift and antigenic drift leads to the development of new strain of Influenza A viruses. Now the novel swine influenza A/H1N1 strain has been detected from different parts of the world which is causing pandemic. World Health Organization has declared the pandemic phase six and more than 60 countries have reported the cases of novel influenza A/H1N1 strain including Nepal. As the disease is spreading world wide, it is a major public health concern for all the countries. And especially the developing countries like Nepal should immediately respond to the situation and should be well prepared to combat the disease before the disease spreads to enough population. PMID- 22049836 TI - Bone and joint decade 2000-2010 in Nepalese perspective. AB - The Bone and Joint Decade is a worldwide multi-disciplinary initiative targeting the care of people with musculoskeletal disorders. It focuses on improving the quality of life of these people through advances in the understanding and treatment through education, research, and prevention strategies. Though the epidemiological data in Nepal are very scanty, worldwide statistics have shown that musculoskeletal conditions represent more than half of all chronic diseases, and are the most common cause of severe long-term pain and disability. There is acute shortage of specialist manpower that care for people with these disorders. Furthermore the teaching in musculoskeletal disorders in health institutions is very minimal. All of these problems highlight the need for expanding the teaching of musculoskeletal disorders at all levels of medical education; promotion of clinical research; improving diagnostic, treatment, and rehabilitative facilities; and implementation of preventive strategies to reduce the burden of these chronic debilitating conditions in the society. PMID- 22049837 TI - High sensitivity C-reactive protein: emerging biomarker for primary prevention of cardiovascular disease. PMID- 22049838 TI - Data scan. With access to a newly available trove of private insurers' claims data, new institute aims to study what's driving spiraling healthcare costs. AB - A new research initiative aims to delve into private-insurer claims data to study utilization and what's driving healthcare costs. The Health Care Cost Institute will help researchers, who have been limited to Medicare data or limited private claims. "We're optimistic. We have nothing to hide here," says Michael Richards, left, of Gundersen Lutheran Medical Center. PMID- 22049839 TI - Obama puts Dems on guard. Some senators wary of healthcare cuts. PMID- 22049840 TI - Three-way fight. Post-acute segments work to ward off cuts. PMID- 22049841 TI - To wait or not to wait .... Decision to go for EHR incentive payments not a simple one for providers. PMID- 22049842 TI - Veiled disclosures. Providers eager to know extent of CMS' leniency for Stark law violators. PMID- 22049843 TI - Pharmacy deal causes waves. Critics: Express Scripts, Medco plan would up prices. PMID- 22049844 TI - Pricey healthcare. Studies show U.S. costs are higher, benefits lower--with blame for all. PMID- 22049845 TI - Keeping the focus on patients. Team-based care, increased access add to a better medical home, panelists say. PMID- 22049847 TI - Taking it to the next level. Judges laud designs for meeting patient demands. PMID- 22049846 TI - Desperation premium. Providers, patients, pharmacies can all work to stop drug price gouging. PMID- 22049848 TI - First consolidation, then coordination. LTAC operators using acquisitions to expand their care continuums. PMID- 22049849 TI - Taking a beating. Healthcare execs see stock holdings, company portfolios nosedive. AB - The pounding that healthcare companies have taken on Wall Street is getting personal for their CEOs, whose holdings at their respective companies are down more than $180 million in value this year. "The key driver of incentives is stock holding. That's where the action is," says Wayne Guay, left, of the Wharton School. Boards may want to consider increasing their CEOs' relative weighting to equity compensation, he says. PMID- 22049850 TI - Readmission questions. With rates static, some wonder if focus helps quality. PMID- 22049851 TI - Approaching with caution. HHS offers another coordinated-care push. PMID- 22049852 TI - 'Quite a jump' in premiu. Medical care declined as prices soared rapidly. PMID- 22049853 TI - Path set for ACA? Proponents, foes of law appeal to Supreme Court. PMID- 22049854 TI - Laws fail to slow gray market. Concerns raised over secondary drug distributors. PMID- 22049855 TI - Painful reminders. New reports add emphasis to the cost and quality challenges in healthcare. PMID- 22049856 TI - Long wait nearly over. ICD-10 implementation now important and urgent ahead of 2013 deadline. PMID- 22049857 TI - Going the distance.ICD-10 compliance deadline still two years off but plenty of hurdles remain for providers, vendors. PMID- 22049858 TI - Accounting abracadabra. New FASB rule will alter how bad debt is reported. PMID- 22049859 TI - Revision rates after total ankle arthroplasty in sample-based clinical studies and national registries. AB - BACKGROUND: The aim of this study was to evaluate the outcome of specific implants in total ankle arthroplasty as reported in clinical studies and determined by national registries. MATERIALS AND METHODS: A structured literature review was conducted regarding sample-based clinical studies and national registry data. To allow for comparative analyses, registry data had to be available for the implants included. These were STAR Ankle, Buchel-Pappas, Hintegra, Mobility, Agility, and Ramses Total Ankle Arthroplasty. The revision rate was used as the main outcome parameter. RESULTS: On average, the revision rates published in sample-based clinical studies were about half the value found in registries. Implant developers represent a share of almost 50% of the published content and are therefore over-represented in scientific publications. The inventors of STAR Ankle and BP total ankle implants published data which was statistically significantly superior to the outcome achieved in average patients as documented in registries. Irrespective of the implant, the average revision rate to be expected according to the registry data available is 21.8% after 5 years, and 43.5% after 10 years. CONCLUSION: The average revision rate published in peer-reviewed scientific articles was significantly lower than the outcome achieved according to national arthroplasty registry data, which reflect actual average patient care in the respective countries. Publications by some research groups, particularly by implant inventors, show a deviation from the outcome published by other users and those shown in registry data. PMID- 22049860 TI - Extracorporeal shock wave treatment of non- or delayed union of proximal metatarsal fractures. AB - BACKGROUND: Nonunion or delayed union of fractures in the proximal aspect of metatarsals 1 to 4 and Zone 2 of the fifth metatarsal were treated by high energy extracorporeal shock wave treatment (ESWT) to study the safety and efficacy of this method of treatment in a FDA study of the Ossatron device. MATERIALS AND METHODS: In a prospective single-arm, multi-center study, 34 fractures were treated in 32 patients (two subjects had two independent fractures) with ESWT. All fractures were at least 10 (range, 10 to 833) weeks after injury, with a median of 23 weeks. ESWT application was conducted using a protocol totaling 2,000 shocks for a total energy application of approximately 0.22 to 0.51 mJ/mm2 per treatment. The mean ESWT application time for each of the treatments was 24.6 +/- 16.6 minutes, and anesthesia time averaged 27.1 +/- 10.4 minutes. All subjects were followed for 1 year after treatment at intervals of 12 weeks, 6, 9, and 12 months. RESULTS: The overall success rate at the 12-week visit was 71% with low complications, significant pain improvement as well as improvement on the SF-36. The success/fail criteria was evaluated again at the 6- and 12-month followup, showing treatment success rates of 89% (23/26) and 90% (18/20), respectively. The most common adverse event was swelling in the foot, reported by five subjects (15.6%). CONCLUSION: High-energy ESWT appears to be effective and safe in patients for treatment of nonunion or a delayed healing of a proximal metatarsal, and in fifth metatarsal fractures in Zone 2. PMID- 22049861 TI - Prospective study of a cementless, mobile-bearing, third generation total ankle prosthesis. AB - BACKGROUND: The SALTO total ankle prosthesis is a noncemented mobile bearing anatomic design characterized by dual Ti-HA coating. This study reviews our results with this prosthesis. MATERIALS AND METHODS: Between 2001 and 2007, 413 consecutive SALTO prostheses were implanted in our institution in 215 women and 198 men, aged 57.1 +/- 11.9 years. At the last visit, 401 implants (47% in the left ankle) were available with a mean followup of 29 (range, 1 to 84) months. RESULTS: Based on the results of the 218 patients with at least 2 years of postoperative followup, the 5-year estimated survivorship, with the primary end point being implant removal, was 86.6% and ranged from 85.1% in patients with post-traumatic osteoarthritis to 95.6% in those with rheumatoid arthritis. The AOFAS score increased from 50.9 +/- 16.8 points preoperatively to 82.2 +/- 14 points at followup (mean difference, 31.1 +/- 1.4, 95% confidence interval (C.I.) for the difference, 28.3 to 33.8, p < 0.001). Visual analog scale for pain decreased from 7.4 +/- 1.1 preoperatively to 2.0 +/- 2.0 postoperatively (mean difference, -5.4 +/- 0.7, 95% C.I. for the difference, -5.6 to -5.2, p < 0.001). Flexion/extension ROM increased from 25.2 +/- 14.1 degrees to 33.1 +/- 13.6 degrees at the last followup visit (mean difference, 7.9 +/- 0.5 degrees, 95% C.I. for the difference, 4.3 to 7.2, p < 0.001), while pronation/supination ROM increased from 23.8 +/- 13.7 degrees to 25.4 +/- 14.5 degrees (mean difference, 1.6 +/- 0.7 degrees, 95% C.I. for the difference, 0.9 to 2.2, p = 0.005). CONCLUSION: The SALTO prosthesis provided good clinical and functional results and we believe helps validate the concept of anatomic replacement. PMID- 22049862 TI - Operative correction of arch collapse with forefoot deformity: a retrospective analysis of outcomes. AB - BACKGROUND: There are many forefoot deformities, including hallux valgus, forefoot overload, and hammertoe that are treated as unrelated problems with multiple different techniques. Currently, there has been renewed interest in the role of a gastrocnemius contracture on foot deformities. Our objective was to review a specific surgical treatment plan for forefoot deformities classified by us as Type 2 arch collapse and evaluate the outcomes. MATERIALS AND METHODS: We retrospectively reviewed the charts of 374 patients who underwent foot procedures to treat deformity classified as a Type 2 arch collapse. Data was collected regarding complications and need for secondary surgery. A phone survey was performed to assess patient satisfaction, pain level, and Foot Function Index (FFI) scores. RESULTS: Of the 374 patients (412 feet), there was a 96% (357 of 371 feet) union rate at the first tarsometatarsal joint and 98% (227 of 232 feet) union rate at metatarsal shortening osteotomy sites. Recurrence of hallux valgus was 2.7% (7 of 256 feet), while hallux varus occurred in 1.6% (4 of 256 feet). There were 292 patients (78%) available for phone interview. Of those patients, 88% were satisfied with the results of the procedure. The subset of procedures relating to the highest mean FFI was hammertoe correction (22.2) and the highest mean pain score was related to metatarsal shortening osteotomy (2.6). CONCLUSION: Utilizing the arch collapse model, operative treatment of forefoot deformities with a combination of procedures including gastrocnemius recession, first TMT fusion, modified McBride, hammertoe correction, and metatarsal shortening osteotomy can produce good satisfaction rates with low complication rates. PMID- 22049863 TI - Trimalleolar fracture with involvement of the entire posterior plafond. AB - BACKGROUND: A special type of trimalleolar fracture with the involvement of the entire posterior tibial plafond has been reported recently. Because of the low incidence, the characteristics of the fracture in different studies have not been consistent. We describe our clinical experience with this fracture type. MATERIALS AND METHODS: From January 2007 to December 2009, 12 patients were identified with a trimalleolar fracture with involvement of entire posterior tibial plafond. All the fractures were openly reduced and fixed through a combined operative approach (posterolateral and posteromedial). Ten of 12 patients were followed up. The clinical outcome was assessed with the Short Form 36 (SF-36) and standardized AAOS foot and ankle questionnaire, and the radiological evaluation with an osteoarthritis-score (OA-score). RESULTS: Based on the pathoanatomy of the posteromedial malleolar fragment, all the fractures could be classified into two types. Using a combined operative approach, anatomical reduction and stable fixation was accomplished in all 12 patients. At a mean followup of 18.9 (range, 12 to 30) months, 10 patients achieved a good radiological result and satisfactory clinical recovery. CONCLUSION: This fracture pattern may be classified into two types with different injury mechanisms, which has not been described previously. After anatomic reduction and stable fixation through a combined operative approach, the short-term outcome was good. PMID- 22049864 TI - Radiographic considerations of hallux valgus versus hallux rigidus. AB - BACKGROUND: Metatarsus primus elevatus (MPE) has long been suggested as a primary causative factor in the pathogenesis of hallux rigidus (HR). The purpose of this investigation was to more clearly define this relationship by comparison of first ray position in patients with hallux rigidus, hallux valgus, and a control population with no known foot pathology. MATERIALS AND METHODS: Clinical and radiographical data were retrospectively collected from 297 patients (394 feet) between the periods of January 2007 and September 2008. Patients were stratified into those having isolated HR (110 patients, 145 feet), isolated hallux valgus (HV) (118 patients, 159 feet), and control group (C) of asymptomatic volunteers (69 patients, 90 feet). Any patient with a previous history of foot trauma, surgery, or other foot or ankle pathology was excluded from the study. Standing lateral weightbearing X-rays were obtained for measurement of first to second metatarsal head elevation (Horton Index), Seiberg Index, and Sagittal Intermetatarsal Angle (IMA). RESULTS: A significant difference in first ray elevation in HR population was identified by all the three measurements. Horton Index (mm) was 6.4 +/- 2.5 for HR population, as compared to 4.0 +/- 2.5 and 3.4 +/- 1.9 for the HV and C populations (p < or = 0.05). Seiberg Index (mm) measured 2.5 +/- 1.8 for the HR group, versus 1.0 < or = 1.6 and 0.24 +/- 0.9 for the HV and C groups respectively (p < or = 0.05). The sagittal IMA (degrees) were 4.5 +/ 2.5 versus 2.7 +/- 2.2 and 1.8 +/- 1.2 (p < or = 0.05). CONCLUSION: This investigation does not show any etiological relation between MPE and HR, but identified a correlation between them. PMID- 22049865 TI - Peroneal tenography to evaluate lateral hindfoot pain after calcaneal fracture. AB - BACKGROUND: Lateral hindfoot pain after union of a calcaneal fracture remains a challenge to orthopaedic surgeons. This study aimed to investigate the relationship between lateral calcaneal pain, calcaneal width and peroneal tendon sheath impingement in patients with lateral hindfoot pain. MATERIALS AND METHODS: Seventy-four consecutive patients with unilateral lateral hindfoot pain were identified from an institutional trauma registry. Regular followups were performed and the severity of lateral hindfoot pain was recorded. CT scans were conducted to measure calcaneal width at the level of sustentaculum tali. Bilateral peroneal tenography was performed to examine compression of the peroneal tendon sheath. The sheaths on the injured, painful side were compared to the contralateral sheath at the same level. The data was analyzed with bivariate correlation using SPSS 13.0 for Windows. RESULTS: The injured calcanei were wider in all patients and the peroneus longus and brevis tendon sheaths were compressed on peroneal tenography in 68.9% (51 of 74). Statistics demonstrated significant correlations between compression of tendon sheaths and lateral hindfoot pain (Rs = 0.93, p < 0.001), and between increasing calcaneal width and lateral hindfoot pain (Rs = 0.665, p < 0.001). The severity of lateral hindfoot pain was directly correlated to tendon sheath impingement and indirectly related to calcaneal widening. CONCLUSION: Calcaneal widening following fracture union was the cause of compression of the peroneal tendons. Increasing compression correlated with increasing levels of lateral pain. Our study demonstrated the utility of peroneal tenography in identifying the presence of peroneal tendon impingement in patients with lateral pain following calcaneal fractures. PMID- 22049866 TI - Radiographic evaluation of foot structure following fifth metatarsal stress fracture. AB - BACKGROUND: Correlation between foot structure and stress fracture risk has not been adequately evaluated or proven. The purpose of this study was to compare foot structure in fracture cases versus control with respect to radiological parameters in stress fractures of the fifth metatarsal. MATERIALS AND METHODS: The study group consisted of 50 consecutive athletes with a diagnosis of fifth metatarsal stress fracture and a control group matched for sport type and age. Fifth metatarsophalangeal (MTP-5) angle, fourth-fifth intermetatarsal (IMA4-5) angle, fifth metatarsal lateral deviation (MT5-LD) angle were measured on standing antero-posterior (AP) radiographs. Talo first metatarsal (T-MT1) angle, talo-calcaneal (TC) angle, and calcaneal pitch (CP) angle were measured on a standing lateral view, and MT5-LD angle was measured on a 30-degree medial oblique view. RESULTS: Significant inter-group differences were found for TC angle (p < 0.001) and calcaneal pitch angle (p < 0.001) on lateral radiographs, and for IMA4-5 angle (p = 0.003), MT5-LD angle (p = 0.002) on AP radiographs, and for MT5-LD angle (p < 0.001) on the 30-degree medial oblique radiographs. CONCLUSION: Fifth metatarsal stress fractures were found to be associated with elevated T-MT1 angle and CP angle representing a cavus foot and the increased curvature of fifth metatarsal. In addition, the extent of fifth metatarsal curvature on a 30-degree medial oblique view was found to be more related to the risk of fracture than on the AP view. PMID- 22049867 TI - Histomorphological evaluation of diabetic and non-diabetic plantar soft tissue. AB - BACKGROUND: Diabetic foot ulceration has a complex and multifactorial etiology and can involve changes in the pathophysiology of the plantar soft tissue. In the current study, histomorphological analyses of diabetic and non-diabetic plantar tissue were performed. It was hypothesized that the diabetic tissue would have thicker skin (epidermis and dermis), less interdigitation between the dermis and epidermis, thicker elastic septa and decreased adipose cell size. MATERIALS AND METHODS: Two locations of the foot (the heel and the first metatarsal) were examined, both of which have been reported to be locations with a high incidence of ulceration. Stereological methods and quantitative morphological techniques were used to evaluate the skin thickness, interdigitation index, elastic septae thickness and adipocyte cell size. RESULTS: The diabetic donors had a greater body mass index (BMI) than the non-diabetic donors. The diabetic tissue had significantly thicker elastic septae and dermis. However, no significant difference was observed in the interdigitation index or adipocyte size. CONCLUSION: These findings demonstrate that morphological changes can be evaluated histologically to give a better understanding of the pathological changes in the plantar soft tissue with diabetes. These evaluations can then be associated with biomechanical changes that occur in diabetes to provide new insight into how microstructural changes can alter macroscopic properties. CLINICAL RELEVANCE: An understanding of the histomorphological changes in the soft tissue in relationship to the location on the foot could help to explain the biomechanical changes that occur in diabetes and the subsequent increase in susceptibility to breakdown. PMID- 22049868 TI - Biomechanical comparison of lag screw versus self-drilling screw fixation of oblique metatarsal osteotomy. AB - BACKGROUND: Several fixation methods for a Weil metatarsal osteotomy have been proposed. Lag screw fixation has been described as the preferred fixation technique. The self-drilling screw has been introduced and can be used for fixation of the Weil osteotomy. The current study compared self-drilling screws with lag screw fixation. MATERIALS AND METHODS: A Weil metatarsal osteotomy was performed on the second, third, and fourth metatarsals of five matched pairs of fresh frozen cadaver feet. The feet of each pair were randomly assigned ical to fixation with either a 2.0-mm cortical lag screw or a 2.0-mm self-drilling screw. The second metatarsals were stressed using cantilever bending. The third and fourth metatarsals were stressed under a shear force. Yield load, deformation at yield load, structural stiffness, and energy stored at yield load were recorded. RESULTS: There were no statistically significant differences (p < 0.05) noted. However, there was a trend toward greater biomechanical stability with the lag screw. CONCLUSION: There were no significant differences in the stability of fixation of the self-drilling screw and lag screw. There was a trend toward the lag screw fixation being more stable. CLINICAL RELEVANCE: The clinical significance of this trend is uncertain but suggests there is not a large difference between the two methods of fixation. PMID- 22049869 TI - Medial approach for hindfoot arthrodesis with a valgus deformity. AB - BACKGROUND: Surgical correction of valgus deformity of the hindfoot has traditionally been via a lateral incision, often complicated by wound healing problems and sural nerve damage. Potential advantages of a medial approach especially for a valgus deformity include excellent wound healing, no risk of damage to the sural nerve and extensibility of the approach to include additional procedures such as navicular fusion or tendon transfer if indicated. MATERIALS AND METHODS: We present a retrospective review of 18 consecutive patients with valgus deformity of the hindfoot, all undergoing arthrodesis via a medial approach. Indications included osteoarthritis, tibialis posterior dysfucntion, post-traumatic arthritis and rheumatoid arthritis. RESULTS: All wounds healed by primary intention and there were no postoperative neurovascular complications. The mean preoperative subtalar valgus deformity was 32 (range, 12 to 49) degrees, which was improved to mean postoperative valgus deformity of 17 (range, 10 to 25) degrees. Fusion following the primary surgery was achieved in all but one of the patients (a heavy smoker and post-traumatic arthritis), with the mean time to fusion being 5.6 months. CONCLUSION: We provide further evidence to support previous documentation in the literature that the medial approach for the correction of hindfoot valgus deformity can be successfully used to achieve excellent exposure of the subtalar joint in order to correct the valgus deformity, avoiding the risks of wound healing and nerve damage associated with a lateral approach. PMID- 22049870 TI - Metatarso-sesamoid osteoarthritis as a cause of pain after first metatarsophalangeal joint fusion: case report. PMID- 22049871 TI - Gout associated with fracture of the fifth metatarsal shaft: a case report. PMID- 22049872 TI - Simple two-portal technique for endoscopic gastrocnemius recession: clinical tip. PMID- 22049874 TI - The house that tech built. The time is now to plug into patient-centered medical home incentives. Here's how to do it. PMID- 22049873 TI - Current concepts review: traumatic disorders of the first metatarsophalangeal joint and sesamoid complex. PMID- 22049875 TI - Selling your practice. Consider several key factors to help you get the most out of your sale. PMID- 22049876 TI - 5 Tips you need to know when buying insurance. Avoid common mistakes such as not enough disability insurance, with too many riders. PMID- 22049877 TI - Do you have the urge to merge? Buying or combining with another practice can lower overhead costs and boost operating efficiencies. PMID- 22049878 TI - Building profits. Don't leave money on the table when it comes to net A/R. PMID- 22049879 TI - Maintaining a connection. We listen to our patients, but in this ever-changing computer era, are we really attending to them? PMID- 22049880 TI - What dying patients want. Volunteering at a hospice shows a retired doctor people's differing needs at the end of life. PMID- 22049881 TI - A matter of respect. A friendship with an unusual patient changes how a young doctor approaches the practice of medicine. PMID- 22049882 TI - Security on the go. Patient data dos and don'ts in the era of mobile access. PMID- 22049883 TI - The roadmap to incentive payments. Follow these steps to get reimbursed for using electronic health records. PMID- 22049884 TI - On-site assessments offer several benefits. PMID- 22049885 TI - A better way in malpractice cases. Mediation could right an unjust legal system. PMID- 22049886 TI - Development of subspecialty within specialty. PMID- 22049887 TI - Color vision defects in school going children. AB - INTRODUCTION: Color vision defect can be observed in various diseases of optic nerve and retina and also a significant number of people suffer from the inherited condition of red and green color defect. METHODS: A cross-sectional descriptive study was designed with purposive sampling of students from various schools of Kathmandu Valley. All children were subjected to color vision evaluation using Ishihara Isochromatic color plates along with other examination to rule out any other causes for color deficiency. RESULTS: A total of 2001 students were examined, 1050 male students and 951 females with mean age of 10.35 (+/- 2.75) and 10.54 (+/- 2.72) respectively. Among the total students examined, 2.1% had some form of color vision defects. Of the male population, 3.9% had color vision defects while none of the female was found with the deficiency. CONCLUSIONS: The prevalence of color vision defect in Nepal is significant and comparable with the prevalence quoted in studies from different countries. PMID- 22049888 TI - Substance use among medical students in Kathmandu valley. AB - INTRODUCTION: Substance use including tobacco and alcohol is the most important cause of preventable morbidity, disability, and premature mortality. The study aims to specify the prevalence and the pattern of use of different substance. METHODS: A cross sectional study was performed amongst first year and final year students in four medical colleges in Kathmandu using self administered anonymous questionnaire.Data collectedfrom 446 students were analyzed. RESULTS: Prevalence of substance use was found to be 60.3% among the medical students. Alcohol (57.6%) was the substance most prevalently used followed by tobacco (27.58%) and cannabis (12.8%). Mean age of first exposure was 17.94 (Confidence interval: 17.91-17.97). There was significant difference in the useof tobacco and cannabis amongst final year students than first year students. Male and female differed significantly in use of every substance except for benzodiazepine. Medical college, college and school were place of first exposure in 17.26%, 15.92% and 13.23% of the cases respectively. Family history was associated with substance use in medical students and was statistically significant (P<0.0001).Experimentation was the major reason for the use of most of the substances. CONCLUSIONS: Substance use is prevalent in male medical students of both first and final year. Hence steps should be initiated early in school, college and medical college to prevent substance use. PMID- 22049889 TI - Measles outbreak among unvaccinated children in Bajura. AB - INTRODUCTION: Measles outbreak occurs when there are three or more laboratory confirmed measles cases in a village in a period of one month. Integrated surveillance system has helped to identify the measles outbreak, to characterize its epidemiology and to timely respond it. METHODS: This is a descriptive study of measles outbreak that occurred in Bajura district in February to March 2010. The epidemiological characteristics of the outbreak are described. The outbreak was investigated from 4-8 March 2010 with necessary epidemiological information and biological specimen collection. One month follow up was done to determine the clinical outcome of the measles cases. RESULTS: A total of 36 people had measles; 97% of them were under 15 years of age and 89% had not been immunized with measles vaccine. Attack rate and vaccine efficacy was 23% and 50% amongst children less than 15 years of age and case fatality rate (CFR) was 3%. Biological samples were collected from 11 patients; all of which tested IgM positive for measles and genotype D8 was isolated. CONCLUSIONS: CFR of this outbreak is higher than the national CFR. Vaccine efficacy of 50% points towards the need for investigation of vaccine logistics and cold chain system. Moreover, this laboratory test confirmed an outbreak showing that the measles virus could be imported from an endemic region and rapidly spread through a susceptible population who were previously not immunized. PMID- 22049890 TI - Antibiotic resistance pattern of bacterial isolates in neonatal care unit. AB - INTRODUCTION: Bacterial infections account for a huge proportion of neonatal deaths worldwide. The problem of antibiotic resistance among common bacterial pathogens mainly the gram negative bacteria is emerging globally which is of more serious concern in developing countries like Nepal. METHODS: A one year retrospective hospital based study was carried out to analyze the results of neonatal blood, cerebrospinal fluid, urine, stool and surface cultures and to look into the sensitivity pattern of the commonly used antibiotics. RESULTS: The positive yield of blood, urine, eye swab and CSF cultures were 19.56%, 38.5%, 60% and 0.36% respectively. The most common isolates in the blood culture were coagulase negative Staphylococcus, Acinetobacter, Enterobacter and non-haemolytic Streptococcus. A significant percent of the isolates were resistant to the first line antibiotics. Among the gram negative isolates more than 30% are resistant to cefotaxime and more than 50% are resistant to gentamicin. During the one year period we had Nursery outbreaks of methicillin resistant Staphylococcus aureus and Salmonella infections. With the help of environmental cultures we were able to trace the source and intervene appropriately. CONCLUSIONS: Continuous surveillance for antibiotic susceptibility, rational use of antibiotics and the strategy of antibiotic cycling can provide some answers to the emerging problem of antibiotic resistance. PMID- 22049891 TI - Ketamine gargling and postoperative sore throat. AB - INTRODUCTION: Tracheal intubation is a foremost cause of trauma to the airway mucosa, resulting in postoperative sorethroat (POST). The aim of the study was to compare the effectiveness of ketamine gargle with placebo in preventing POST after endotracheal intubation. METHODS: Forty patients scheduled for elective surgery under general anaesthesia were enrolled in this randomized, control trial. Patients were randomly allocated into two groups of 20 patients each: Group C, gargling with drinking water 30 ml; Group K, gargling with ketamine 50 mg in drinking water 30 ml for 30 s, 5 min before induction of anaesthesia. POST was graded at 4, 8, and 24 hours respectively after operation on a four- point scale (0-3). RESULTS: POST occurred more frequently in Group C, when compared with Group K at 4, 8, and 24 hours. CONCLUSIONS: Ketamine gargle reduces the incidence of POST after endotracheal intubation. PMID- 22049892 TI - Outcome of preterm babies and associated risk factors in a hospital. AB - INTRODUCTION: Preterm birth is a major problem associated with maximum perinatal mortality and morbidity in developed and developing countries. The aim of this study is to identify risk factors associated with preterm birth and to study morbidities and mortality. METHODS: A descriptive retrospective study was conducted on 164 cases of preterm babies admitted to Neonatal Intensive Care Unit from January, 2007 to December, 2009 RESULTS: Incidence of preterm birth was 19.5%. Mean birth weight was 1670 +/- 370 grams and mean gestational age was 30.02 +/- 0.37 weeks. Common risk factor associated with preterm birth were inadequate antenatal checkup (52%), maternal age <20 years (34.7%), ante partum hemorrhage (23.4%) and pregnancy induced hypertension (13.1%). Common morbidities were clinical sepsis (66.7%), hyperbilirubinemia (58.8%), birth asphyxia (26.8%) and hyaline membrane disease (23.5%). Overall survival was 79.4% with minimum age of survival of 880 grams. The mortality rate in extremely low birth rate and very low birth rate was 80% and 39.5% respectively. The common causes of death were hyaline membrane disease (64.5%), sepsis (58.06%) and necrotizing enterocolitis (25.8%). CONCLUSIONS: The main risk factors for preterm delivery were inadequate antenatal check up, maternal age <20 years, antepartum hemorrhage and pregnancy induced hypertension. The most common morbidity was clinical sepsis followed by hyperbilirubinemia. Common causes of death were hyaline membrane disease and sepsis. PMID- 22049893 TI - Effective control of hypertension in adults with chronic kidney disease. AB - INTRODUCTION: Adequate control of hypertension in Chronic Kidney Disease patients is difficult to achieve. This study was designed to analyze the adequacy of Hypertension control in adults with CKD using different classes of antihypertensive drugs. METHODS: A cross-sectional observational study was done that included 85 patients with CKD admitted to our Medicine Department over a period of two years (2006-2008 A.D.). Presence of CKD was defined as glomerular filtration rate <60 ml/min per 1.73 m2 for more than three months or presence of albuminuria (albumin:creatinine ratio >30ug/mg). Adequate blood pressure control was defined as systolic blood pressure less than or equals to 130 and diastolic blood pressure less than or equals to 80 mm Hg. Data and Statistical analysis was done using SPSS Version 12 for Windows. RESULTS: Of all the CKD patients, 51.4% required three Anti-Hypertensive drugs combination for the effective control of Hypertension, while only 21% of CKD patients with hypertension was controlled on two drugs. CONCLUSION: Adequate control of blood pressure in CKD patient was shown to be most effective on combination of three antihypertensive drugs. A poor control was seen on patients taking less than three antihypertensive drugs. PMID- 22049894 TI - Conservative treatment in acute appendicitis. AB - INTRODUCTION: Acute appendicitis is one of the commonest surgical problems and appendectomy is one of the most commonly done operations in the emergency world wide. Though there have been occasional reports with conservative treatment in acute appendicitis, it is not being practiced as a routine. METHODS: All patients between ten to sixty years of age admitted at BPKIHS with the diagnosis of acute appendicitis over a period of one year were enrolled in the study. After taking informed consent the patients were managed conservatively. Those who did not respond to antibiotics within 24 hours were operated. Total hospital stay and complications were recorded and they were followed up at first week, sixth week and sixth month. The success rate, conversion rate, recurrence rate and morbidity and mortality pattern were assessed as the final outcome of conservative treatment of acute appendicitis. RESULTS: A total of 96 patients (48 males and 48 females) underwent conservative treatment. The conservative treatment was successful in 79 (82.3%) cases and failed in 11 (11.4%) cases, which included: conversion to appendectomy during conservative treatment period 4 (4.2%) cases, recurrence 7 (7.3%) cases. There was no mortality in this study. CONCLUSION: Acute appendicitis can be treated successfully with conservative (antibiotics) treatment with a short hospital stay. Though there is a risk of recurrence in some cases, all the complications after appendectomy can be eliminated with the conservative treatment. PMID- 22049895 TI - Pralidoxime in organophosphorus poisoning. AB - INTRODUCTION: Pralidoxime are enzyme reactivator that are known to reactivate the phosphorylated acetylcholinesterase by binding to the organophosphorus molecule. The use of oximes in acute organophosphorus poisoning has been a controversial subjects for over two decades. This study was conducted with the objective to find out the estimation of serum cholinesterase and use of pralidoxime in organophosphorus poisoning. METHODS: A prospective analysis of all organophosphorus poisoning cases presented at the Emergency Department, Tribhuvan University Teaching Hospital for seven months was done. RESULTS: Out of 26 cases about 60% of poisoning cases were monitored for pseudocholinesterase level. About 50% of them had pseudocholinesterase level within normal limit and 20% had less than 10% of normal value. Only 33% cases with pseudocholinesterase level less than 10% were treated with pralidoxime. CONCLUSIONS: The initial dose of Pralidoxime used was 1 gm followed by maintenance dose of 500mg 6 hourly, the doses prescribed were less than WHO recommended doses. PMID- 22049896 TI - Curved knife "Khukuri" injury in the back and anaesthesia induction in lateral position for thoracotomy. AB - Penetrating injury in the back with knife (Khukri) demands induction of anaesthesia and intubation in lateral position. In thoracic injury a double lumen tube placement is required to facilitate one lung ventilation during thoracotomy. In emerging situation, we could successfully execute induction of patient in right lateral position using right sided DLT for left thoracotomy. Its correct placement was confirmed by fiberoptic bronchoscopy. In conclusion right-DLT intubation can be performed without difficulty by conventional direct laryngoscopy using Macintosh blade in lateral position. PMID- 22049897 TI - Local resection of gastrointestinal stromal tumor of the second part of duodenum. AB - Gastrointestinal stromal tumors are relatively rare in the duodenum, representing 2-4% of Gastrointestinal stromal tumors of the gastrointestinal tract. We describe a huge Gastrointestinal stromal tumor arising from the second part of the duodenum invading the transverse colon which was removed successfully by local resection of the second part of the duodenum along with a segment of transverse colon. PMID- 22049898 TI - Bilateral eventration of sciatic nerve. AB - During routine dissection of a 60 years male cadaver, it was observed that the two divisions of sciatic nerve were separate in the gluteal region on both the sides with the tibial nerve passing below the piriformis and the common peroneal nerve piercing the piriformis muscle. The abnormal passage of the sciatic nerve (SN), the common peroneal nerve (CPN), and the tibial nerve (TN), either through the piriformis or below the superior gemellus may facilitate compression of these nerves. Knowledge of such patterns is also important for surgeons dealing with piriformis syndrome which affects 5-6% of patients referred for the treatment of back and leg pain. A high division may also account for frequent failures reported with the popliteal block. PMID- 22049899 TI - Enteric fever with severe pancytopenia in a four year girl. AB - Typhoid fever and paratyphoid fever (also known as enteric fever) are severe systemic illnesses caused by salmonella typhi and S. paratyphi respectively. Enteric fever is prevalent in developing countries including Nepal, where it still remains as a major health problem. There have been reports of pancytopenia with enteric fever which has been attributed to mechanisms like bone marrow suppression, infection associated hemophagocytic syndrome and disseminated intravascular coagulation. We report here a case of severe pancytopenia in enteric fever as a result of bone marrow suppression due to systemic infection. PMID- 22049900 TI - Abstruse diagnosis of obturator hernia--a case series. AB - The diagnosis of obturator hernia is one of suspicion as it is almost never seen and rarely palpated. The incidence is less than 1% of all hernias worldwide. Five cases of obturator hernias are reported where the diagnosis of obturator hernia were overlooked. PMID- 22049901 TI - Disease mongering in psychiatry: fact or fiction? AB - Disease mongering starts at the top of recent accusations being hurled at psychiatry. It is used to refer to the attempts by pharmaceutical companies or others who have similar interests, to enlarge the market for a treatment by convincing people that they are sick and need medical intervention. This paper critically analyses the 'for' and 'against' arguments of disease mongering in psychiatric disorders, both new and old, such as Bipolar disorders, attention deficit hyperactivity disorder, Restless legs syndrome, Premenstrual dysphoric disorder, female sexual dysfunction, social phobia, metabolic syndrome and road rage disorder. PMID- 22049902 TI - Residents' work schedule and patient safety. PMID- 22049903 TI - General practice specialist in Nepal. PMID- 22049904 TI - Life as a medical officer in peripheral government health institution. PMID- 22049905 TI - History of syphilis. PMID- 22049906 TI - Nail lichen planus: epidemiological, clinical, pathological, therapeutic and prognosis study of 67 cases. AB - BACKGROUND: Lichen planus limited to the nail is uncommon, and information about its long-term prognosis is lacking. OBJECTIVES: We attempted to review the epidemiological, clinical and histological features, the response to treatment and the follow-up of a large series of patients with nail lichen planus (NLP). METHODS: We searched for the records of all patients with a clinical and histopathological diagnosis of isolated NLP apart from January 1997 to December 2008. The patients presented during this period and followed until December 2009 in the consultation for nail disorder were reviewed in detail. RESULTS: Data on 67 patients were collected, with an average age of 47 years (6-78 years). A male preponderance was observed (64%). The mean duration of the disease was about 38 months. Fingernails were the site of involvement in 94% of cases. Matrix involvement was observed in 91% of cases. A total of 120 specimen's biopsy were taken and was contributory in 90% of cases. Two specimens biopsy were practiced in 70.15% of patients. Systemic corticosteroids were used in 46 patients, and associated in 20 cases to intralesional corticosteroids. CONCLUSIONS: Our findings indicate that if NLP is correctly diagnosed and appropriately treated. Nail biopsy is proven to be a relatively simple, safe and useful procedure with a minimal scarring risk. Long-term observation indicates that the prognosis of NLP is poor with high rate of relapses, with permanent damage to the nail unit. PMID- 22049907 TI - Dephosphorylation reactions with deferoxamine, a potential chemical nuclease. AB - We report a detailed kinetic and mechanistic study of the reaction of a widely used therapeutic agent, deferoxamine (DFO), which contains three nucleophilic hydroxamate groups, with the model phosphate diester bis-2,4 dinitrophenylphosphate BDNPP. We clarify the mechanism by detecting important phosphorylated intermediates in the model reaction and show that the mechanism can be extended to the reaction with DNA. The effectiveness of DFO in cleaving DNA was examined over a range of pH in the absence and presence of a biologically available metal (Zn(2+)). The results inform and complement ongoing studies involving DFO, which can act as a powerful nucleophile toward DNA and other targets susceptible to nucleophilic attack. PMID- 22049909 TI - The cytotoxic effects of preserved and preservative-free prostaglandin analogs on human corneal and conjunctival epithelium in vitro and the distribution of benzalkonium chloride homologs in ocular surface tissues in vivo. AB - PURPOSE: To investigate the cytotoxicity of benzalkonium chloride (BAC) containing ophthalmic solutions of prostaglandin analogs (latanoprost, travoprost, bimatoprost, and preservative-free (PF) tafluprost), BAC mixture (BACmix) and BAC homologs with different alkyl chain lengths using human corneal epithelial (HCE) and conjunctival epithelial (IOBA-NHC) cell cultures. The distribution of BAC homologs in rabbit ocular surface tissues in vivo was examined. METHODS: The cells were exposed for one hour to prostaglandin analogs, BACmix and three homologs. Cytotoxicity was assessed with the WST-1 and lactate dehydrogenase (LDH) assays for cellular viability and cell membrane integrity. BAC 0.02% solution was instilled on the rabbit eye daily for 14 days and the concentrations of BAC homologs in external ocular tissues were determined. RESULTS: The order of decreasing cytotoxicity in the WST-1 test was latanoprost >= travoprost > bimatoprost >= PF tafluprost. IOBA-NHC cells were more sensitive than HCE cells. In HCE, only latanoprost diluted to 10% increased LDH leakage. In IOBA-NHC, LDH leakage was statistically significant with 3-10% travoprost and 10% latanoprost. The order of decreasing cytotoxicity of preservatives was C14 > C12 > BACmix > C16 in HCE and C12 > C14 > BACmix > C16 in IOBA-NHC. Following treatment with BAC 0.02% solution, the amounts of BAC-C12, -C14 and -C16 in rabbit cornea and conjunctiva, respectively were: 0.37 +/- 0.08 and 2.64 +/- 0.27 ng/mg; 0.42 +/- 0.07 and 4.77 +/- 0.43 ng/mg; 0.04 +/- 0.01 and 0.54 +/- 0.05 ng/mg. CONCLUSIONS: The cytotoxic effects of latanoprost, travoprost, and bimatoprost were dependent on the BAC concentration in their formulations. BACmix was cytotoxic at the concentrations above those corresponding to 0.001% BAC in ophthalmic medications. PF tafluprost was the least toxic of the drugs tested. Within studied BAC homologs, those with longer alkyl chain and higher lipophility penetrated effectively into rabbit external ocular tissues. PMID- 22049908 TI - Phylogenetic analysis of the Latvian HIV-1 epidemic. AB - The Latvian HIV-1 outbreak among intravenous drug users (IDUs) in 1997-1998 involved subtype A1. To obtain a more complete picture of the Latvian HIV-1 epidemic, 315 HIV-1-infected patients diagnosed in 1990-2005 representing different transmission groups and geographic regions were phylogenetically characterized using env V3 and gag p17 sequences. Subtypes A1 and B infections were found in 76% and 22% of the patients, respectively. The subtype A1 sequences formed one large cluster, which also included sequences from other parts of the former Soviet Union (FSU), whereas most subtype B sequences formed three distinct clusters. We estimated that subtype A1 was introduced from FSU around 1997 and initially spread explosively among IDUs in Riga. A recent increase of heterosexually infected persons did not form a separate subepidemic, but had multiple interactions with the IDU epidemic. Subtype B was introduced before the collapse of the Soviet Union and primarily has spread among men who have sex with men. PMID- 22049910 TI - Full-length human glutaminase in complex with an allosteric inhibitor. AB - Glutaminase (GLS1/2) catalyzes the conversion of L-glutamine to L-glutamate and ammonia. The level of a splice variant of GLS1 (GAC) is elevated in certain cancers, and GAC is specifically inhibited by bis-2-(5-phenylacetimido 1,2,4,thiadiazol-2-yl)ethyl sulfide (BPTES). We report here the first full-length crystal structure of GAC in the presence and absence of BPTES molecules. Two BPTES molecules bind at an interface region of the GAC tetramer in a manner that appears to lock the GAC tetramer into a nonproductive conformation. The importance of these loops with regard to overall enzymatic activity of the tetramer was revealed by a series of GAC point mutants designed to create a BPTES resistant GAC. PMID- 22049911 TI - Apigenin, a plant-derived flavone, activates transient receptor potential vanilloid 4 cation channel. AB - BACKGROUND AND PURPOSE: Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+) -permeable channel with multiple modes of activation. Apigenin is a plant derived flavone, which has potential preventive effects on the development of cardiovascular disease. We set out to explore the effects of apigenin on TRPV4 channel activity and its role in vasodilatation. EXPERIMENTAL APPROACH: The effects of apigenin (0.01-30 uM) on TPRV4 channels were investigated in HEK293 cells over-expressing TRPV4, rat primary cultured mesenteric artery endothelial cells (MAECs) and isolated small mesenteric arterial segments using whole-cell patch clamp, fluorescent Ca(2+) imaging, intracellular recording and pressure myography. KEY RESULTS: Whole-cell patch clamp and fluorescent Ca(2+) imaging in HEK cells over-expressing TRPV4 showed that apigenin concentration-dependently stimulated the TRPV4-mediated cation current and Ca(2+) influx. In MAECs, apigenin stimulated Ca(2+) influx in a concentration-dependent manner. These increases in cation current and Ca(2+) influx were markedly inhibited by TRPV4 specific blockers and siRNAs. Furthermore, pressure myography and intracellular recording in small third-order mesenteric arteries showed that apigenin dose dependently evoked smooth muscle cell membrane hyperpolarization and subsequent vascular dilatation, which were significantly inhibited by TRPV4-specific blockers. TRPV4 blocker or charybdotoxin (200 nM) plus apamin (100 nM) diminished the apigenin-induced dilatation. CONCLUSION AND IMPLICATIONS: This is the first study to demonstrate the selective stimulation of TRPV4 by apigenin. Apigenin was found to activate TRPV4 channels in a dose-dependent manner in HEK cells over expressing TRPV4 and in native endothelial cells. In rat small mesenteric arteries, apigenin acts on TRPV4 in endothelial cells to induce EDHF-mediated vascular dilatation. PMID- 22049912 TI - Mometasone furoate dry powder inhaler for the treatment of asthma. AB - INTRODUCTION: Asthma is a chronic inflammatory disease that causes significant morbidity and mortality. Inhaled corticosteroids are the preferred initial treatment for this disorder. Mometasone furoate dry powder is an inhaled corticosteroid that is approved for once-daily treatment of asthma in both adults and children as young as 4 years. AREAS COVERED: The goal of this paper is to review the clinical efficacy and safety of mometasone furoate dry powder inhaler for the treatment of asthma. A literature search using PubMed was done using the terms 'mometasone furoate', 'inhaled corticosteroid' and 'asthma', focusing on articles that highlighted clinical trials and addressed efficacy of the medication. EXPERT OPINION: Mometasone furoate dry powder inhaler has an excellent safety and efficacy profile. For patients with persistent asthma who require treatment with an inhaled corticosteroid, mometasone furoate is an excellent therapeutic choice. PMID- 22049913 TI - The impact of low serum sodium level on mortality depends on glycemic control. AB - BACKGROUND: Low serum sodium levels have been associated with mortality both in patients with and without chronic kidney disease. In this study, we investigated this association in relation to glycemic control in hemodialysis (HD) patients. MATERIALS AND METHODS: Between March and September 2005, 697 prevalent HD patients were enrolled in this prospective observational study and followed up for all-cause and cardiovascular mortality. The associations of serum sodium concentration with both overall and cardiovascular survival rates were studied. RESULTS: At baseline, mean predialysis serum sodium concentration was 138.4 +/- 2.3 mEq/L (range: 130-145 mEq/L). Mild hyponatremia (< 135 mEq/L) was present in only 41 subjects (5.9%), and no patient had serum sodium level < 130 mEq/L. During 20.2 +/- 6.2 months of follow-up, 119 patients (15.9%) died, 68 from CV causes. In adjusted Cox regression analysis, lowest sodium quartile was associated with 2.13-fold increased risk of overall mortality (95% confidence interval (CI) 1.14-3.98, P = 0.01, model chi-square 114.6, P < 0.001). As a continuous variable, each 1 mEq/L increase in predialysis sodium concentration was associated with a hazard ratio (HR) of 0.87 for overall mortality (95% CI 0.81-0.95, P = 0.002) and 0.86 for cardiovascular mortality (95% CI 0.78-0.96, P = 0.007). The predictivity of low serum sodium was prominent in diabetic subjects but not in nondiabetics. However, relationship between serum sodium and patient survival in diabetics was lost after adjustment for the HbA1c level: HR 0.91 (95% CI 0.78-1.05, P = 0.20). CONCLUSIONS: Low serum sodium concentration is associated with mortality only in those with diabetes. Furthermore, the impact of serum sodium on survival in these patients seems to be derived from poor glucose control. PMID- 22049914 TI - How to target postablation perimitral flutter: valve isthmus or PV triggers? PMID- 22049915 TI - Family quality of life in Nigeria. AB - BACKGROUND: The limited literature that exists about intellectual disabilities (ID) in Nigeria suggests that perceptions of ID may be shaped by social and cultural beliefs, and that socio-economic factors have prevented the development of policy and services. The present study sought to explore these suggestions in more detail by administering the Family Quality of Life Survey, an instrument used extensively throughout the world to collect comprehensive data on family quality of life. Its specific purposes were: (1) to describe the family quality of life of Nigerian families that have a son or daughter with ID and (2) to provide some initial ideas about the relationship between the families' life experiences and government policy and provision of services. METHOD: Eighty main caregivers from 80 families that received services for their sons and daughters with ID from two community agencies volunteered to participate. Two trained assistants administered the Family Quality of Life Survey in accordance with the administration methods set out by the Survey authors. Quantitative data and explanatory comments were also collected. RESULTS: Regarding the first study purpose, all nine life domains of the Family Quality of Life Survey were rated as important. The two main outcome measures, Attainment and Satisfaction, showed that three domains (Family relationships, Influence of values and Health) were sources of quality for families, but that three domains (Support from services, Support from others and Leisure) detracted from family quality of life. Measures of Opportunities, Initiative and Stability were somewhat related to one another, and with the two main outcome measures. Participants' explanatory comments suggested that the main caregivers perceived some domains to make their lives better and others did not. Regarding the second study purpose, it was only possible with the data available to make suggestions, but it seemed that there is a strong need for the development of government policy and services, and for education and training. CONCLUSIONS: The results of this study suggest that some areas of family life contribute to quality of life for Nigerian families and other areas of life are problematic for families. Although this study is not representative of all Nigerian families that have a son or daughter with ID, it provides important initial information on the family experience with disability in Nigeria. PMID- 22049916 TI - Ammonia removal using activated carbons: effect of the surface chemistry in dry and moist conditions. AB - The effect of surface chemistry (nature and amount of oxygen groups) in the removal of ammonia was studied using a modified resin-based activated carbon. NH(3) breakthrough column experiments show that the modification of the original activated carbon with nitric acid, that is, the incorporation of oxygen surface groups, highly improves the adsorption behavior at room temperature. Apparently, there is a linear relationship between the total adsorption capacity and the amount of the more acidic and less stable oxygen surface groups. Similar experiments using moist air clearly show that the effect of humidity highly depends on the surface chemistry of the carbon used. Moisture highly improves the adsorption behavior for samples with a low concentration of oxygen functionalities, probably due to the preferential adsorption of ammonia via dissolution into water. On the contrary, moisture exhibits a small effect on samples with a rich surface chemistry due to the preferential adsorption pathway via Bronsted and Lewis acid centers from the carbon surface. FTIR analyses of the exhausted oxidized samples confirm both the formation of NH(4)(+) species interacting with the Bronsted acid sites, together with the presence of NH(3) species coordinated, through the lone pair electron, to Lewis acid sites on the graphene layers. PMID- 22049917 TI - Alcohol use among young men who have sex with men. AB - This study reveals associations between alcohol use and demographic variables, as well as the relation between alcohol use and sexual activity, using episodic data. Data were obtained during summer and fall 2008 from a sample of 558 gay, bisexual, and other young men who have sex with men (YMSM), ages of 13-29 years in New York City. Recruitment strategies targeted potential participants at gay related venues and public spaces often frequented by YMSM. Alcohol use varied by race/ethnicity, with White YMSM consuming significantly more alcohol than other races/ethnicities. Participants over the age of 21 drank significantly more alcohol than participants ages 13-20. Alcohol use was not found to be associated with sexual risk-taking activity. Our findings are enriched by a large, diverse sample of urban YMSM. Study limitations are noted. PMID- 22049919 TI - "Turn-on" chemiluminescence sensor for the highly selective and ultrasensitive detection of Hg2+ ions based on interstrand cooperative coordination and catalytic formation of gold nanoparticles. AB - Monitoring the levels of potentially toxic metal ions such as Hg(2+) in aquatic ecosystems is important because this ion can have severe effects on human health and the environment. Thus, a novel chemiluminescence (CL) sensor is developed for the highly selective and ultrasensitive detection of Hg(2+) ions in aqueous solution, based on thymine-Hg(2+)-thymine (T-Hg(2+)-T) coordination chemistry and subsequent formation of gold nanoparticles (Au NPs) in a HAuCl(4)/NH(2)OH reaction. The thus-formed Au NPs trigger the reaction between luminol and AgNO(3), producing CL emission. This novel CL technique has several advantages including high sensitivity (0.01 ppb) and selectivity over a spectrum of interfering metal ions. In view of these advantages, as well as the cost effective, minimized working steps and portable features of the CL techniques, we expect that this CL sensor will be a promising candidate for the field detection of toxic Hg(2+) ions in environment, water, and food samples. PMID- 22049920 TI - Improved DFT description of intrastrand cross-link formation by inclusion of London dispersion corrections. AB - The formation of covalent linkages between two vicinal nucleotides has been proved experimentally to constitute a particularly deleterious class of DNA lesions. These tandem lesions by essence present a competitive chemistry. The density functional theory with dispersion (DFT-D) method is shown to dramatically improve the theoretical description of the formation of a prototypical intrastrand cross-link, when compared to pure or hybrid GGA functionals which strongly deviate from the pi-pi self-stacking mode, as dinucleotides are artificially stabilized by the formation of unrealistic intramolecular hydrogen bonds (HBs). Inclusion of London dispersion correction restores a more realistic picture of the reactant structure and also of geometries and energies along the reaction profile. This paves the way toward a robust insilico screening of intrastrand cross-link DNA defects. PMID- 22049921 TI - A novel mutation of CYLD in a Chinese family with multiple familial trichoepithelioma. AB - BACKGROUND: Trichoepithelioma is a benign cutaneous tumour that originates from hair follicles and occurs either as a sporadic non-familial or a multiple familial type. Recently, several mutations in the cylindromatosis (CYLD) gene have been reported in multiple familial trichoepithelioma (MFT). OBJECTIVES: To report a Chinese family of MFT and to explore the genetic mutation. METHODS: A Chinese pedigree of typical MFT was subjected to mutation detection in CYLD. Direct sequencing of all PCR products of the whole coding regions of CYLD gene was performed to identify the mutation. RESULTS: The c.1178-1179delCA (p.T393fs) mutation was found in CYLD gene in the affected members, but not in the healthy individuals in the family. CONCLUSION: Our study found a novel mutation in exon 10 of CYLD gene. PMID- 22049922 TI - Design and methodology of POWER, an open-label observation of the effect of primary care interventions on total cardiovascular risk in patients with hypertension. AB - This article describes the design and methodology of the POWER study (Physicians' Observational Work on Patient Education According to their Vascular Risk). POWER is an open-label multinational postmarketing study of the angiotensin II-receptor blocker eprosartan. The Systemic Coronary Risk Evaluation (SCORE) model has been used to estimate total cardiovascular risk and changes in total cardiovascular risk status during treatment for patients recruited in all countries other than Canada. Framingham Heart Study equations have been used to estimate risk in the Canadian contingent of POWER. Observations from POWER will provide insights into how clinicians try to achieve blood pressure goals within the framework of total cardiovascular risk management and how they integrate their treatment of blood pressure with other interventions. Experience during the POWER study may also help to affirm the utility, practicability and perhaps limitations of the SCORE system for estimating total cardiovascular risk and identify ways to improve the acceptance and implementation of risk estimation methods in cardiovascular primary prevention. PMID- 22049923 TI - Psychiatric comorbidities in patients with alopecia areata in Taiwan: a case control study. AB - BACKGROUND: Alopecia areata (AA) may be related to stress and has been reported to be associated with psychiatric disorders. Nevertheless, a nationwide study of the relationship between AA and comorbid psychiatric diseases has not been conducted, and the effect of onset age has rarely been reported. OBJECTIVES: To analyse the associations between AA and various psychiatric disorders using a nationwide database in Taiwan. METHODS: Data were obtained from the National Health Insurance Research Database of Taiwan from 2000 to 2009. In total, 5117 patients with AA and 20 468 age- and gender-matched controls were enrolled. RESULTS: Patients with AA tended to have more coexisting anxiety and less comorbid schizophrenia. Differences in ages of onset revealed differences in comorbidities. An increased risk of depression [odds ratio (OR) 2.23; 95% confidence interval (CI) 1.09-4.54] was found in patients with AA aged < 20years. An increased rate of anxiety (OR 1.43; CI 1.15-1.77) was observed with AA onset between the ages of 20 and 39years. The highest odds of obsessive-compulsive disorder (OR 3.00; CI 1.11-8.12) and anxiety (OR 2.05; CI 1.56-2.68) were observed in patients with AA aged 40-59years. Moreover, about 50% of psychiatric disorders occurred earlier than AA. CONCLUSIONS: AA is related to various psychiatric disorders. Onset age of AA is an important factor in the association with different comorbid psychiatric diseases. In addition to cosmetic impact, which may bring about anxiety or depression, stress neuroendocrine immunology may play an important role in the pathogenesis of both AA and psychiatric disorders. PMID- 22049924 TI - Formation of high aspect ratio GaAs nanostructures with metal-assisted chemical etching. AB - Periodic high aspect ratio GaAs nanopillars with widths in the range of 500-1000 nm are produced by metal-assisted chemical etching (MacEtch) using n-type (100) GaAs substrates and Au catalyst films patterned with soft lithography. Depending on the etchant concentration and etching temperature, GaAs nanowires with either vertical or undulating sidewalls are formed with an etch rate of 1-2 MUm/min. The realization of high aspect ratio III-V nanostructure arrays by wet etching can potentially transform the fabrication of a variety of optoelectronic device structures including distributed Bragg reflector (DBR) and distributed feedback (DFB) semiconductor lasers, where the surface grating is currently fabricated by dry etching. PMID- 22049925 TI - Tumor suppressor p16INK4a controls oncogenic K-Ras function in human pancreatic cancer cells. AB - Pancreatic cancer is characterized by oncogenic activation of K-Ras and inactivation of the cell cycle inhibitor p16(INK4a) . We previously demonstrated that reintroduction of p16(INK4a) reversed anoikis resistance and clonogenicity of human pancreatic cancer cells, properties commonly attributed to the transforming potential of oncogenic K-Ras. Therefore, we aimed to determine the role of Ras after p16(INK4a) re-expression. Here, we show that restitution of p16(INK4a) in pancreatic cancer cell lines elicits a profound suppression of K Ras activity. A more detailed analysis in p16(INK4a) reconstituted Capan-1 cells indicated selective reduction of both K-Ras activity and protein stability. Re expression of K-Ras in p16(INK4a) restituted Capan-1 cells reversed the anoikis sensitive phenotype and increased colony formation, indicating that K-Ras suppression was required for p16(INK4a) -mediated reversion of the transformed phenotype. Inducible expression of p16(INK4a) in DanG cells confirmed inhibition of K-Ras activity as well as an increase in anoikis susceptibility. Thus, our results delineate a novel functional interaction with defined biological consequences for the two most frequent alterations observed in pancreatic cancer. PMID- 22049926 TI - Probiotics prevent the development of 1,2-dimethylhydrazine (DMH)-induced colonic tumorigenesis through suppressed colonic mucosa cellular proliferation and increased stimulation of macrophages. AB - Probiotics modulate immunity and inhibit colon carcinogenesis in experimental models, but these effects largely depend on the bacterial strain, and the precise mechanisms are not well understood. Therefore, we studied the effect of Bifidobacterium longum and/or Lactobacillus gasseri on the development of 1,2 dimethylhydrazine (DMH)-induced colonic precancerous lesions and tumors in mice while delineating the possible mechanisms involved. The results suggest that dietary consumption of probiotics (B. longum and L. gasseri) resulted in a significant inhibition of DMH-induced aberrant crypt foci (ACF) formation in male ICR mice. Long-term (24 weeks) dietary consumption of probiotics resulted in a reduction of colon tumor multiplicity and the size of the tumors. Administration of B. longum and L. gasseri suppressed the rate of colonic mucosa cellular proliferation in a manner correlating with the inhibition of tumor induction by DMH. In addition, the phagocytic activity of peritoneal macrophages was significantly increased in the DMH-treated mice that were fed various doses of B. longum, but not with L. gasseri or combined probiotics (B. longum + L. gasseri). We also found that L. gasseri significantly increased the proliferation of RAW264.7 macrophage cells through an increase in S phase DNA synthesis, which was related to the up-regulation of proliferating cell nuclear antigen (PCNA) and cyclin A. Taken together, these results demonstrate the in vivo chemopreventive efficacy and the immune stimulating mechanisms of dietary probiotics against DMH induced colonic tumorigenesis. PMID- 22049930 TI - Operative Dentistry Home Page. PMID- 22049927 TI - Are mental health problems and depression associated with bruxism in children? AB - OBJECTIVES: Previous studies have found an association between bruxism and emotional and behavioral problems in children, but reported data are inconsistent. The objective of this study was to estimate the prevalence of bruxism, and of its components clenching and grinding, and its associations with mental problems and depression. METHODS: Data from two Brazilian birth cohorts were analyzed: one from 869 children in Ribeirao Preto - RP (Sao Paulo), a more developed city, and the other from 805 children in Sao Luis - SL (Maranhao). Current bruxism - evaluated by means of a questionnaire applied to the parents/persons responsible for the children - was defined when the habit of tooth clenching during daytime and/or tooth grinding at night still persisted until the time of the assessment. Additionally, the lifetime prevalence of clenching during daytime only and grinding at night only was also evaluated. Mental health problems were investigated using the Strength and Difficulties Questionnaire (SDQ) and depression using the Children's Depression Inventory (CDI). Analyses were carried out for each city: with the SDQ subscales (emotional symptoms, conduct problems, peer problems, attention/hyperactivity disorder), with the total score (sum of the subscales), and with the CDI. These analyses were performed considering different response variables: bruxism, clenching only, and grinding only. The risks were estimated using a Poisson regression model. Statistical inferences were based on 95% confidence intervals (95% CI). RESULTS: There was a high prevalence of current bruxism: 28.7% in RP and 30.0% in SL. The prevalence of clenching was 20.3% in RP and 18.8% in SL, and grinding was found in 35.7% of the children in RP and 39.1% in SL. Multivariable analysis showed a significant association of bruxism with emotional symptoms and total SDQ score in both cities. When analyzed separately, teeth clenching was associated with emotional symptoms, peer problems, and total SDQ score; grinding was significantly associated with emotional symptoms and total SDQ score in RP and SL. Female sex appeared as a protective factor for bruxism, and for clenching and grinding in RP. Furthermore, maternal employment outside the home and white skin color of children were associated with increased prevalence of teeth clenching in SL. CONCLUSIONS: Mental health problems were associated with bruxism, with teeth clenching only and grinding at night only. No association was detected between depression and bruxism, neither clenching nor grinding. But it is necessary to be cautious regarding the inferences from some of our results. PMID- 22049931 TI - Reflection and reasoning in moral judgment. AB - While there is much evidence for the influence of automatic emotional responses on moral judgment, the roles of reflection and reasoning remain uncertain. In Experiment 1, we induced subjects to be more reflective by completing the Cognitive Reflection Test (CRT) prior to responding to moral dilemmas. This manipulation increased utilitarian responding, as individuals who reflected more on the CRT made more utilitarian judgments. A follow-up study suggested that trait reflectiveness is also associated with increased utilitarian judgment. In Experiment 2, subjects considered a scenario involving incest between consenting adult siblings, a scenario known for eliciting emotionally driven condemnation that resists reasoned persuasion. Here, we manipulated two factors related to moral reasoning: argument strength and deliberation time. These factors interacted in a manner consistent with moral reasoning: A strong argument defending the incestuous behavior was more persuasive than a weak argument, but only when increased deliberation time encouraged subjects to reflect. PMID- 22049932 TI - Physiology of biosurfactant synthesis by Rhodococcus species H13-A. AB - The physiology of biosurfactant synthesis by a soil isolate, identified as a Rhodococcus species, is described. The biosurfactant is a surface-active glycolipid produced during the stationary growth phase of Rhodococcus species H13 A on n-alkanes and fatty alcohols in response to limiting ammonium ion concentrations. Hexadecane-grown cells produced increasing amounts of extracellular glycolipid when the carbon to nitrogen ratio (C/N) was increased from 1.7 to 3.4. The increase in extracellular glycolipid in hexadecane-grown cells correlated with a decrease in the interfacial tension of the spent growth medium to values less than 5 mN/m. Significant levels of extracellular glycolipid were not detected in the spent growth medium of cells grown on triglycerides, fatty acids, ethanol, organic acids, or carbohydrates. Rhodococcus species H13-A contains the three indigenous plasmids pMVS100, pMVS200, and pMVS300, with neither pMVS200 nor pMVS300 being involved in glycolipid synthesis or hexadecane dissimilation. The role of pMVS100 remains undetermined. Key words: biosurfactants, glycolipids, trehalose lipids, Rhodococcus. PMID- 22049933 TI - Physical and chemical properties of a biosurfactant synthesized by Rhodococcus species H13-A. AB - The chemical and physical properties of a biosurfactant synthesized by hexadecane grown Rhodococcus species H13-A are described. The biosurfactant is an anionic glycolipid consisting of 1 major and 10 minor components. The hydrophilic portion of the molecule is trehalose, which is acylated with normal C(10) to C(22) saturated and unsaturated fatty acids, C(35) to C(40) mycolic acids, hexanedioic and dodecanedioic acids, and 10-methyl hexadecanoic and 10-methyl octadecanoic acids. The major glycolipid species was identified as 2,3,4,6,2',3',4',6' octaacyltrehalose, plus minor glycolipid species of di-, tetra- and hexa acyltrehalose derivatives. The glycolipid exhibited a critical micelle concentration of 1.5 mg/mL and minimum interfacial tension value of 2 * 10(-2) mN/m against decane, with a further reduction in interfacial tension to 6 * 10( 5) mN/m in the presence of the cosurfactant pentanol. The phase behavior of the glycolipid indicates the formation of a surfactant-rich, "middle-phase" microemulsion containing liquid crystals, both of which are associated with surfactant systems having ultralow interfacial tension values. Key words: trehalose lipids, glycolipids, biosurfactants. PMID- 22049934 TI - Production of amylases by yeasts. AB - Yeasts (228) isolated for natural habitats were screened for their ability to produce amylases in semisolid medium of wheat bran. Strains of Aureobasidium pullulans, Candida famata, and Candida kefyr showed high enzymatic activity for alpha-amylase, glucoamylase, and debranching enzyme. Key words: Aureobasidium, Candida, amylolytic yeasts, alpha-amylase, glucoamylase. PMID- 22049935 TI - Selection of strains of Epicoccum purpurascens for tolerance to fungicides and improved biocontrol of Sclerotinia sclerotiorum. AB - A wild-type isolate of Epicoccum purpurascens was exposed to shortwave ultraviolet light. One of the resulting cultures (M-20-A) was grown on media amended with the fungicides iprodione or vinclozolin and fungicide-tolerant strains were obtained. Several comparisons were made between new strains and the wild type. Sporulation was improved compared with the wild type. Strains varied in their tolerance to iprodione and vinclozolin but were not tolerant to the fungicide benomyl. Strains R4000, 16-B, and 7-A inhibited Sclerotinia sclerotiorum in vitro more than either the wild type or M-20-A, and exhibited improved control of white mold of bean in the greenhouse compared with M-20-A. Key words: biological control, fungicide resistance, white mold, iprodione, vinclozolin. PMID- 22049936 TI - Identification of a denitrifying gliding bacterium, isolated from soil and able to reduce nitrous oxide in the presence of sulfide and acetylene, as Flexibacter canadensis. AB - We have reexamined the properties of a gliding bacterium, Is-11, which was previously isolated from soil because of its ability to denitrify and to reduce nitrous oxide in the presence of sulfide and normally inhibitory concentrations of acetylene. Occurrence of such an organism may have important implications for the use of the acetylene inhibition assay for measuring denitrification rates in reduced, sulfidic environments. Although originally tentatively identified as a Cytophaga sp., extensive morphological, physiological, and biochemical tests as well as G+C analysis and DNA hybridization studies now indicate that the soil isolate Is-11 is a strain of Flexibacter canadensis. Key words: gliding bacteria, Flexibacter canadensis, denitrification, acetylene, sulfide, nitrous oxide. PMID- 22049937 TI - Involvement of cell surface sugars in recognition, attachment, and appressorium formation by a mycoparasite. AB - Fluorescein isothiocyanate labeled lectin binding techniques have revealed differences in the distribution pattern of glycosyl residues at the cell wall level between fungi that are hosts and those that are nonhosts of the mycoparasite Piptocephalis virginiana, and at the protoplast level between compatible and incompatible hosts. The cell wall of the compatible hosts (Choanephora cucurbitarum and Mortierella pusilla) and an incompatible host (Phascolomyces articulosus), as well as that of the mycoparasite itself, contains glucose and N-acetylglucosamine. However, the cell wall of a nonhost (Mortierella candelabrum) tested positive with lectins specific for various sugars, including not only glucose and N-acetylglucosamine, but also fucose, N-acetylgalactosamine, and galactose. These latter sugars could also be exposed at the surfaces of hosts and of the mycoparasite, but only after mild treatment with proteinase or when grown in a liquid culture. Pretreatment of the mycoparasite with glucose and N acetylglucosamine inhibited its attachment to the host cell surface, but had no obvious effect on appressorium formation. On the other hand, appressorium formation was inhibited by heat treatment of host cell wall fragments which still permitted attachment, thus indicating that the factors responsible for attachment and for appressorium formation are different. The protoplast surfaces of compatible hosts contained all the sugars listed above and these protoplasts could attach to the germ tube of the mycoparasite. Only lectins specific for N acetylglucosamine and for glucose were bound at the protoplast surface of the incompatible host; these protoplasts did not attach to the mycoparasite germ tube. Key words: mycoparasite, appressorium formation, lectins, host cell surface, attachment, protoplast surface. PMID- 22049938 TI - Nitrate reduction to ammonia: a dissimilatory process in Enterobacter amnigenus. AB - Thirty-four bacterial isolates from an agricultural soil anaerobically preincubated in the presence of glucose were tested for their ability to reduce nitrate to ammonia or to denitrify in two different media: nitrate broth and a minimal medium enriched with glucose. Ten isolates were considered denitrifying bacteria and 7 were dissimilatory ammonia producers. Ammonia production by the isolate identified as Enterobacter amnigenus was quantified and attained 50% of 138 mg?L(-1) of added NO(3)(-) N. The dissimilatory character of this reduction was clearly confirmed by culturing this (15)N-labeled bacterium in the presence of unlabeled nitrite. Nitrous oxide was produced at the same time as nitrite was reduced to ammonia. Increasing nitrate N levels from 48 to 553 mg?L(-1) in culture medium resulted in an increase in the level of nitrite produced and simultaneously a decrease in ammonia and nitrous oxide production. Key words: dissimilatory nitrate reduction, dissimilatory ammonia production, denitrification, Enterobacter amnigenus, (15)N. PMID- 22049939 TI - Dissimilatory ammonia production vs. denitrification in vitro and in inoculated agricultural soil samples. AB - A dissimilatory ammonia-producing isolate identified as Enterobacter amnigenus and a denitrifier identified as Agrobacterium radiobacter isolated from the same soil were studied. The products of nitrate reduction in a minimal medium, enriched with glucose and containing nitrate N as the sole nitrogen source, were quantified when each of these isolates was cultured anaerobically, alone or mixed together in the presence or absence of C(2)H(2). When they were cultured together, ammonia was the principal product of nitrate reduction. The distribution between denitrification and dissimilatory ammonia production (DAP) for nonsterilised soil samples inoculated with E. amnigenus or A. radiobacter, or a mixture of these two isolates, was also investigated. Production of NH(4)(+) was increased under these conditions (strict anaerobiosis and much available fermentable carbon), but the inoculation of soil samples with 1.2 * 10(7) cells of E. amnigenus.g dried soil(-1) was not sufficient to shift nitrate reduction from nitrous oxide (denitrification) to ammonia production, suggesting that inoculation with a greater number of DAP bacteria than introduced would probably be required to enable ammonia production to exceed nitrous oxide release. Key words: dissimilatory ammonia production, denitrification, Enterobacter amnigenus, Agrobacterium radiobacter. PMID- 22049940 TI - Persistence of introduced Bradyrhizobium japonicum strains in forming nodules in subsequent years after inoculation in Wisconsin soils. AB - Nodulation of soybeans by indigenous and inoculum strains of Bradyrhizobium japonicum was studied in field experiments in Wisconsin from 1983 to 86. Aqueous suspensions of bacteria were applied to seeds at the time of planting at levels of 7 * 10(7)-10(10) bacteria per 2.5-cm row. The predominant indigenous serogroup was 123 in these soils. Six different inoculum strains were used (two from serocluster 123, two from serogroup 110, and one each from serogroups 122 and C1). Nodule occupants were identified using spontaneous antibiotic-resistant mutations in the inoculum strains, phage typing, and serotyping. In the 1983 experiment, the majority of nodules were formed by the inoculum strains in almost all cases (up to 100% in some cases), in two different soils containing 3.5 * 10(5) indigenous B. japonicum per gram. After 2 years without inoculation at the same two site, the inoculum strains did not form many nodules on uninoculated soybeans (less than 10% in most cases; less than 30% in all cases). In inoculation experiments carried out in 1985 and 1986, four inoculum strains were used (3 members of 123 serocluster and USDA 110str); inocula containing 10(8) bacteria per 2.5-cm row formed less than42%ofthe nodules in soils containing 1 * 10(4)-4 * 10(4)B. japonicum per gram. The major conclusions are (i) the success of inoculation in Midwestern U.S. soils is highly variable, even with members of the (highly competitive) 123 serocluster, and (ii) successful inoculation in 1 year in a Wisconsin soil does not ensure that the inoculated strain will persist in forming nodules in that field in subsequent years without further inoculation. Key words: Bradyrhizobium japonicum, strain persistence, field trials. PMID- 22049941 TI - Erratum: Variation in epitopes of the B subunit of Vibrio cholerae non-O1 and Vibrio mimicus cholera toxins. PMID- 22049942 TI - Single site laparoscopic surgery: an intermediate step toward no (visible) scar surgery or the next gold standard in minimally invasive surgery? PMID- 22049943 TI - Successful cholecystectomy during robotic gastrectomy. AB - BACKGROUND: Surgeons have successfully combined various laparoscopic procedures with increasing technical ease. However, few reports exist regarding the feasibility of combined robotic operations. We present our institution's successful concomitant robotic surgery for early gastric cancer and coexisting gallbladder disease. MATERIAL AND METHODS: From our prospectively collected database, seven patients who received robotic cholecystectomies during their robotic gastric cancer operations were retrospectively compared to 247 patients who underwent robotic gastrectomies alone. Preoperative patient characteristics, operative factors, postoperative length of stay, and complications were evaluated. RESULTS: The preoperative patient characteristics and operative factors did not differ between the two groups. All robotic cholecystectomies were performed with the same ports and instruments used during robotic gastrectomies without open conversion, robot redocking or patient repositioning. Mean time to perform robotic cholecystectomies was 15.1 + 3.2 minutes. The combined group had no mortality, one wound infection, and one intraabdominal fluid collection at the gastric resection bed, which were comparable to the gastrectomy alone group. The mean postoperative length of hospital stay was unaltered by the addition of the cholecystectomy. CONCLUSIONS: Robotic cholecystectomies can safely and efficiently be combined with robotic gastric cancer surgery, yielding several benefits. Improving robotic technology and experience may allow surgeons to efficiently combine more complicated procedures. PMID- 22049944 TI - Clinical use of a neuronavigation system in hemangioblastoma resection of posterior cranial fossa. AB - The aim of this study was to retrospectively evaluate the effectiveness of the Stryker Leibinger neuronavigation system in surgical resection of hemangioblastomas of the posterior fossa. The study included 16 cases of solid hemangioblastoma of posterior cranial fossa treated since we began using Stryker Leibinger neuronavigation system-assisted microneurosurgery in 2003. These cases were compared on the basis of time, blood loss, and complications to 19 similar cases of solid hemangioblastoma that underwent conventional microneurosurgical resection prior to 2003. All patients in the experimental (neuronavigation assisted) group underwent surgical resection without complications while the control groups' resections all involved blood loss related to the longer operation time. Neuronavigation also resulted in a clear field of surgical vision and clear lesion boundaries, making it easier to remove lesions and reduce accidental injury of adjacent normal structures. The application of navigation technology is very valuable for solid hemangioblastoma operations not only by shortening operative time, thereby significantly reducing operative blood loss, but also by making surgical excision easier, reducing damage to adjacent normal structures, and decreasing surgical complications and mortality. PMID- 22049945 TI - LESS technique for liver resection: the progress of the mini-invasive approach: a single-centre experience. AB - INTRODUCTION: During the last years, the safety and efficacy of the laparoscopic approach for liver masses located in the left lobe have been demonstrated, encouraging the mini-invasive approach and, in more recent times, the LESS technique (Laparo Endoscopic Single Site), in an attempt to reduce the biological invasiveness related to surgical trauma. MATERIAL AND METHODS: From January 2009 to December 2010, 39 patients underwent laparoscopic liver resection at our institution. In 14 of these, the LESS technique was used. The aim of our study is to evaluate the short-term outcome of this group of patients. RESULTS: We recorded the following results: Mean operative time of 187 min (range 145-420 min), mean intraoperative blood loss of 214 ml (range 50-700 ml), postoperative morbidity rate of 21.4%, one postoperative death (related to acute heart failure related to severe aortic valve stenosis). Excluding this patient from the statistical analysis, the morbidity rate was 14.3%. The median hospital stay was five days. DISCUSSION: The LESS technique for liver resections is safe and effective in selected patients and in centres with high expertise in laparoscopic liver surgery. PMID- 22049946 TI - Analysis of protease and reverse transcriptase genes of HIV for antiretroviral drug resistance in Jamaican adults. AB - This study reports on the drug resistance profiles for HIV-infected adults in Jamaica using genotypic methods. The genetic diversity of HIV-1 found in these patients was also determined using phylogenetic analysis. Epidemiological data were documented for each patient, blood was collected by venous puncture, and plasma was separated and stored. Viral RNA was extracted and analyzed for mutations in the viral genome by the amplification of the protease and reverse transcriptase (Pro-RT) regions using a nested PCR method. The rate of drug resistance among treatment-experienced individuals was 35%, while treatment-naive individuals showed a prevalence of 29%. The overall prevalence of drug resistance mutations in Jamaicans was consistent with the increased use of antiretroviral drugs in the region, with many of the mutations detected reducing susceptibility to the drugs commonly used to treat Jamaican patients. These results indicate the need for regular drug resistant surveillance to guide treatment strategies. PMID- 22049947 TI - Crystal structures of prethrombin-2 reveal alternative conformations under identical solution conditions and the mechanism of zymogen activation. AB - Prethrombin-2 is the immediate zymogen precursor of the clotting enzyme thrombin, which is generated upon cleavage at R15 and separation of the A chain and catalytic B chain. The X-ray structure of prethrombin-2 determined in the free form at 1.9 A resolution shows the 215-217 segment collapsed into the active site and occluding 49% of the volume available for substrate binding. Remarkably, some of the crystals harvested from the same crystallization well, under identical solution conditions, diffract to 2.2 A resolution in the same space group but produce a structure in which the 215-217 segment moves >5 A and occludes 24% of the volume available for substrate binding. The two alternative conformations of prethrombin-2 have the side chain of W215 relocating >9 A within the active site and are relevant to the allosteric E*-E equilibrium of the mature enzyme. Another unanticipated feature of prethrombin-2 bears on the mechanism of prothrombin activation. R15 is found buried within the protein in ionic interactions with E14e, D14l, and E18, thereby making its exposure to solvent necessary for proteolytic attack and conversion to thrombin. On the basis of this structural observation, we constructed the E14eA/D14lA/E18A triple mutant to reduce the level of electrostatic coupling with R15 and promote zymogen activation. The mutation causes prethrombin-2 to spontaneously convert to thrombin, without the need for the snake venom ecarin or the physiological prothrombinase complex. PMID- 22049948 TI - A case of an apparent infestation by Proisotoma spp. springtails (Collembola: Isotomidae) in a cat. AB - This case report is presumed to be the first case of infestation of a cat by springtails which are small arthropods closely related to insects. The organisms, found by skin scrapings, were identified as Proisotoma spp. (Collembola: Isotomidae). The cat presented with dermatological lesions (itchy, furfuraceous dermatitis), and we speculate that they were due to this infestation. The pathogenic role of the Collembola was hypothesized because of the large number of organisms, the presence of eggs indicating an active reproduction cycle, the lack of other pathogens (fleas, mites or lice) and the clinical recovery accompanied by the disappearance of Collembola following treatment. The owner seemed to be affected by the infestation, because a few days after having purchased the cat, she developed a pruriginous papular dermatitis on the neck and the arms, which disappeared shortly after treatment of the kitten and a careful washing of all of its toys and other accoutrements. PMID- 22049949 TI - Efficacy of repeat magnetic resonance imaging of the knee. AB - A patient often initially presents to an orthopedic surgeon with the magnetic resonance image (MRI) ordered by his or her primary care physician in hand. Often, a significant period of time elapses after injury before the patient is assessed by the orthopedic surgeon; therefore, the initial MRI may be considered outdated because of a new injury or a change in symptoms or because the orthopedist may prefer a new study, a stronger magnet, or a special imaging protocol. However, the decision to repeat a knee MRI is presently an arbitrary one because no clinical guidelines exist to justify this practice.All repeat knee MRIs performed at our academic institution in the past 9 years were retrospectively examined. Inclusion criterion was repeat MRI of the same knee with no surgical intervention. The formal radiology reports were grouped into 3 categories: change, no change, and unclear. Knee pathology was further grouped into 6 categories indicating what specific structures were pathological or injured. Logistic regression analysis was used to test the association of time vs category or condition change between MRIs. Of 3501 knee MRI studies, 88 patients had a total of 101 repeat MRIs. The average number of days between repeats for those with category or condition change was 612 vs 504 for those with no change. Age, sex, and time between MRIs were not significantly associated with a category or condition change. Repeat knee MRI prior to surgical intervention is becoming more prevalent and may have clinical merit. A further prospective study is warranted. PMID- 22049950 TI - Randomized prospective evaluation of injection techniques for the treatment of lateral epicondylitis. AB - Lateral epicondylitis is a commonly made diagnosis for general practitioners and orthopedic surgeons. Corticosteroid injection is a mainstay of early treatment. However, conflicting evidence exists to support the use of steroid injection, and no evidence in the literature supports an injection technique. Nineteen patients diagnosed with acute lateral epicondylitis were evaluated to compare the peppered and single-injection techniques using the Disabilities of the Arm, Shoulder and Hand (DASH) score, visual analog score (VAS), and grip strength. For elbows with a single injection, mean grip strength increased from 22.9 to 27.8 (P=.053), mean VAS pain score decreased from 4.8 to 3.6 (P=.604), and mean DASH score decreased from 2.6 to 1.8 points (P=.026). For elbows with peppered injections, mean grip strength increased from 28.7 to 32.8 (P=.336), mean VAS pain scores decreased from 3.7 to 2.3 (P=.386), and mean DASH score decreased from 2.6 to 1.3 (P=.008).No studies have directly compared the peppered-injection technique to the single-injection technique. Our results suggest that patient outcome is improved with the single injection. The biomechanical or chemical reason for the distinction is yet unknown, but we postulate that the peppered technique may actually further damage the already compromised tendon. The theory that the peppered injection stimulates blood flow may be overestimated or false. Histochemical studies of the pathologic tissue must be performed to further delineate the reason for improved outcomes with the single-injection technique. PMID- 22049951 TI - Subcutaneous anterior transposition versus decompression and medial epicondylectomy for the treatment of cubital tunnel syndrome. AB - A review of the literature often fails to uncover the best procedure for the treatment of cubital tunnel syndrome. This article compares 2 frequently used methods (subcutaneous anterior transposition vs decompression and medial epicondylectomy) for their effectiveness in relieving both subjective and objective symptoms of cubital tunnel syndrome. Between August 1991 and October 1993, nineteen patients underwent surgical decompression by a single surgeon for ulnar neuropathy at the elbow. Factors evaluated included upper extremity range of motion, elbow valgus stress, grip strength, pinch, 2-point discrimination, and pre- and postoperative nerve conduction. A standardized questionnaire was administered to assess subjective relief of symptoms.In the transposition group, grip strength averaged 71.2% of normal and pinch strength 86.6% of normal, and 2 point discrimination averaged 8.0 mm. The derived subjective assessment score was 23.2 of a possible 40. The average ulnar motor conduction velocity across the elbow was 50.1 m/sec preoperatively and 56.3 m/sec postoperatively. In the medial epicondylectomy group, grip strength averaged 79.5% of normal and pinch strength 81.7% of normal, and 2-point discrimination averaged 8.0 mm. The average ulnar motor conduction velocity across the elbow was 45.7 m/sec preoperatively and 55.7 m/sec postoperatively. No statistically significant difference existed between the 2 groups for the aforementioned indexes. These results do not indicate a difference between the outcomes of the patients undergoing either of the procedures. Because epicondylectomy is less technically demanding, with less soft tissue dissection of the nerve, it may be preferred over ulnar transposition. PMID- 22049952 TI - Comparing hook plates and Kirschner tension band wiring for unstable lateral clavicle fractures. AB - The purpose of this study was to compare outcomes and complications of clavicular hook plate and Kirschner tension band wiring for fixation of unstable lateral clavicle fractures. The surgical outcomes of 92 consecutive patients (mean age, 49.30 +/- 15.54 years) with unstable fractures of the lateral clavicle treated using AO clavicle hook plates were compared with those of 24 patients (mean age, 50.67 +/- 17.58 years) treated using K-wire tension banding. Patients in the hook plate and K-wire groups were followed up for 22.76 +/- 2.22 and 25.67 +/- 2.75 months, respectively (P<.001). The time to hardware removal was significantly shorter (P<.001) in the hook plate group (5.20 +/- 1.93 months) compared with the K-wire group (7.58 +/- 2.00 months), whereas the Constant-Murley score was significantly higher (P<.001) in the hook plate group (90.43 +/- 4.78) compared with the K-wire group (85.63 +/- 5.38) at final follow-up. There were 12 complications in the hook plate group and 7 in the K-wire group (P=.069). Complications in the hook plate group included 7 periprosthetic fractures, 4 plate removals, and 1 plate malposition. Complications in the K-wire group included 3 K-wire migrations, 3 losses of reduction, and 1 wire breakage. We found that hook plate fixation of unstable lateral clavicle fractures was associated with statistically better shoulder function and earlier implant removal than K-wire tension band fixation, with an equivalent rate of complications. Our findings suggest that hook plates are useful for treating unstable lateral clavicular fractures. PMID- 22049953 TI - Outcomes of modified 2-incision technique with use of indomethicin in treatment of distal biceps tendon rupture. AB - Multiple surgical techniques for distal biceps tendon ruptures exist. Heterotopic ossification is an associated omplication of the 2-incision technique. The purpose of this study was to review the results of distal biceps tendon repairs via the modified 2-incision technique using indomethacin chemoprophylaxis. A retrospective review of 34 2-incision repairs of the distal biceps tendon was performed. All patients received 6 weeks of indomethacin treatment postoperatively to prophylax against heterotopic ossification. Outcome measures included disabilities of the arm, shoulder, and hand (DASH) scoring, incidence of heterotopic ossification, and forearm range of motion. Of the 34 elbows, 2 had minor complications that resolved within 6 weeks of presentation. The average DASH score at final follow-up was 3.8. No cases of heterotopic ossification, nerve palsies, reruptures, or radioulnar synostoses were observed. At final follow-up, no significant difference was noted in range of motion between the injured and uninjured extremity in all planes. The Morrey modification of the 2 incision technique can be safe and provide full functional recovery in patients with ruptured distal biceps tendons when performed in conjunction with indomethacin prophylaxis. PMID- 22049954 TI - Staged bone grafting following placement of an antibiotic spacer block for the management of segmental long bone defects. AB - Segmental long bone defects resulting from injury or surgical intervention are difficult problems to manage. Amputation, external fixators, vascularized fibular grafts, acute limb shortening, and various quantities of allograft and autograft have historically been the mainstays of treatment. Recently, the use of osteoinductive substances such as recombinant bone morphogenic proteins, and osteoconductive scaffolds such as calcium phosphate have found use in the treatment of these clinical situations. More recently, Masquelet described the use of a cement spacer placed within the osseous void followed by staged bone grafting within the induced biomembrane formed around the spacer as a potential treatment strategy to manage these large defects.This article describes a series of 11 patients for which we used this technique of staged bone grafting following placement of an antibiotic spacer to successfully manage osseous long bone defects ranging from 4 to 15 cm. The limbs were stabilized and aligned at the time of initial spacer placement with a plate and screw construct, intramedullary nail, or fine wire fixator. Osteoinductive substances including bone morphogenic protein-2 and platelet rich concentrate were used in addition to allograft to improve bony healing. In our series, osseous consolidation and full weight bearing was achieved in 10 of 11 patients. Two patients developed heterotopic ossification. There was 1 non-union and 1 infection, which occurred in the same patient. Staged bone grafting within an induced biomembrane created after the use of a cement spacer is a reasonable option in the management of both acute and delayed segmental long bone defects. PMID- 22049955 TI - Infected total femoral replacements: evaluation of limb loss risk factors. AB - A complication of total femoral replacement (TFR) is periprosthetic infection. Studies have shown that infected endoprostheses have a significant amputation rate, as high as 36.7%. This study examined possible risk factors that may attribute to unsalvageable TFRs following periprosthetic infections, including age, sex, primary vs secondary TFRs, number of irrigation and debridements, recent history of periprosthetic infection, early vs late infection, use of antibiotic cement, and the number of postoperative antibiotics. In a retrospective chart review, 10 patients who had periprosthetic infections of their TFRs were identified from our orthopedic surgical database between 2000 and 2010. Seven of 10 TFRs were unsalvageable due to infection. The 2 greatest risk factors that influenced unsalvageable TFR were age older than 50 years and recipients of secondary TFRs. All 6 patients older than 50 years had unsalvageable TFRs, whereas 1 of 4 patients younger than 50 years had an unsalvageable TFR (P<.05). Similarly, all 6 patients who received secondary TFRs had unsalvageable TFRs, whereas 1 of 4 patients who received a TFR as the primary method of treatment had an unsalvageable TFR (P<.05). No other risk factors showed statistical significance or could be identified as possible risk factors. Surgeons should educate patients who fall into high-risk categories about the benefits of early intervention, such as amputation, that could prevent additional surgeries and decrease the lengths of hospitalizations. PMID- 22049956 TI - Proximal epiphysis of the second metatarsal: normal trait, possible contribution to growth, and clinical implications. AB - Analysis of 998 dorsoplantar foot radiographs of 231 patients was performed. Age ranged between 0.21 and 19.94 years. The authors proved the existence of a previously nondescribed additional proximal ossification center in the second metatarsal. This additional proximal center was seen in 78 of 998 radiographs, which corresponds with 7 of the 231 patients. If only 111 patients within the age range in which the additional proximal center appears are considered, the true prevalence of the additional proximal center was found in 7 (6.3%) patients. This additional proximal center was found to be bilateral in 4 (57.1%) of these 7 patients. The presence of the proximal center was more common in girls and was associated with index plus metatarsal type (P=.000) and foot pathology, especially flatfoot (P=.000). Age of appearance was 2.3 +/- 0.24 years and age of fusion was 5.5 +/- 2.2 years. Using a descriptive maturation scale, the authors classified the ossification stages of the additional proximal center in 4 stages: rudimentary, fully formed, partially fused, and fully fused. After creating a mathematical ratio, the authors could not prove that the presence of this additional proximal center increased the length of the second metatarsal or the complete second ray. PMID- 22049957 TI - Feasibility of whole-body MRI for detecting metastatic myxoid liposarcoma: a case series. AB - No feasible method currently exists to evaluate systemic metastasis in patients with myxoid liposarcoma. The purpose of this study was to determine the feasibility of performing whole-body magnetic resonance imaging (MRI) to detect metastatic myxoid liposarcoma. From June 2008 to May 2010, all patients who were newly diagnosed with myxoid liposarcomas at our institution underwent whole-body MRI along with other conventional imaging methods. We divided the whole body into 38 sections (7 soft tissue sections and 31 bone tissue sections). In total, there were 570 regions (105 soft tissue regions and 465 bony regions) in 15 patients (10 men and 5 women) who underwent whole-body MRI.Of 105 soft tissue regions, there were 4 true positives, 3 false positives, 1 false negative, and 97 true positives. Of 465 bone tissue regions, there were 11 true positives, 5 false positives, 2 false negatives, and 447 true negatives. In soft tissue, whole-body MRI for the detection of metastatic lesion showed a sensitivity of 80%, a specificity of 97.0%, a positive predictive value of 57.1%, and a negative predictive value of 99.0%. In bone tissue, whole-body MRI had a sensitivity of 84.6%, a specificity of 98.9%, a positive predictive value of 68.8%, and a negative predictive value of 99.6%.Whole-body MRI is feasible and effective for detecting bone and soft tissue metastasis in patients with myxoid liposarcoma. PMID- 22049958 TI - Hibernomas: clinicopathological features, diagnosis, and treatment of 17 cases. AB - Hibernomas are rare benign adipose tumors composed of brown fat cells with granular, multivacuolated cytoplasm admixed with white adipose tissue. They account for 1.6% of benign lipomatous tumors and approximately 1.1% of all adipocytic tumors. They are more common in the third and fourth decades of life. The most common location is the thigh, followed by the shoulder, back, and head and neck. Four histological types have been reported; abundant vascularity is characteristic, and atypias are rare. The treatment of choice for hibernomas is complete surgical excision. Metastases or malignant transformation have not been reported.This article presents a series of 17 patients with hibernomas diagnosed and treated at our institution from January 1986 to December 2009. Six men and 11 women (M:F, 1:2) had a mean age of 38 years (range, 10 months to 64 years). All patients underwent surgical treatment; 14 patients had marginal and 3 had wide excision. Adjuvants such as radiation therapy, chemotherapy, or embolization were not administered for any patient. The most common symptom was a painless palpable mass, followed by a tender or painful mass; in 2 patients, the tumor was an incidental finding. The duration of symptoms ranged from 1 month to 10 years (mean, 27 months). The most common location was the thigh, followed by the buttock, scapula, and neck. The most common histological variant was the typical variant followed by the lipoma-like variant. At a mean follow-up of 5 years (range, 1-9 years), local recurrences were not observed. PMID- 22049959 TI - Lumbar lordosis restoration following single-level instrumented fusion comparing 4 commonly used techniques. AB - A major sequelae of lumbar fusion is acceleration of adjacent-level degeneration due to decreased lumbar lordosis. We evaluated the effectiveness of 4 common fusion techniques in restoring lordosis: instrumented posterolateral fusion, translumbar interbody fusion, anteroposterior fusion with posterior instrumentation, and anterior interbody fusion with lordotic threaded (LT) cages (Medtronic Sofamor Danek, Memphis, Tennessee). Radiographs were measured preoperatively, immediately postoperatively, and a minimum of 6 months postoperatively. Parameters measured included anterior and posterior disk space height, lumbar lordosis from L3 to S1, and surgical level lordosis.No significant difference in demographics existed among the 4 groups. All preoperative parameters were similar among the 4 groups. Lumbar lordosis at final follow-up showed no difference between the anteroposterior fusion with posterior instrumentation, translumbar interbody fusion, and LT cage groups, although the posterolateral fusion group showed a significant loss of lordosis (-10 degrees ) (P<.001). Immediately postoperatively and at follow-up, the LT cage group had a significantly greater amount of lordosis and showed maintenance of anterior and posterior disk space height postoperatively compared with the other groups. Instrumented posterolateral fusion produces a greater loss of lordosis compared with anteroposterior fusion with posterior instrumentation, translumbar interbody fusion, and LT cages. Maintenance of lordosis and anterior and posterior disk space height is significantly better with anterior interbody fusion with LT cages. PMID- 22049960 TI - Do protective lead garments harbor harmful bacteria? AB - This study attempted to identify and characterize bacteria present on shared-use protective lead shielding garments worn in the operating room. Those worn at the authors' institution were collected and swabbed in designated 5*5-cm areas. Swabs were sent to the clinical laboratory for bacterial isolation and identification. All isolates were identified using standard microbiological methods. Isolates then underwent antimicrobial susceptibility testing as per standard hospital procedures. Of 182 total collected swabs, bacteria were isolated on only 5 (2.7%) samples. Coagulase-negative Staphylococci was identified on 3 samples and the remaining 2 grew coagulase-negative Staphylococci and gram-positive rods. The collection sites for these isolates were the lead apron, midline, bottom outer surface (n=3), thyroid shield midline, inner surface (n=1), and skirt midline, bottom inner surface (n=1). Of the collected samples, 98.3% were negative for bacterial growth. The remaining isolates were consistent with common skin flora. No multi-drug resistant organisms were identified on any garments. Standard cleaning procedures at the institution are an effective way to prevent growth of bacteria on shared-use protective lead shielding garments worn in the operating room. PMID- 22049961 TI - Malignant mixed tumor of the soft tissue occurring after total knee arthroplasty. AB - A 70-year-old woman developed a malignant mixed tumor of the soft tissue 2 years after total knee arthroplasty. A 5*3*3-cm elastic hard tumor at the lateral side of the surgical scar was resected. The tumor showed focal infiltration into surrounding adipose and fibrous tissues, focal necrosis, and vascular infiltration. It was diagnosed as malignant. Mixed tumor, or myoepithelioma, of the soft tissue is a relatively rare tumor that was recently recognized as a disease entity; the vast spectrum of myoepithelial cell differentiation and the resultant morphologic diversity might increase the difficulty of the histological diagnosis. Postoperatively, the patient did not receive adjuvant therapy and no recurrence of the tumor was observed for 6 years. Range of motion of her left knee is -5 degrees extension and 90 degrees flexion; however, her activities of daily living are restricted because of general fatigue, partly due to hepatoma and chemotherapy.Despite the increase of artificial implant use worldwide, reports of peri-implant tumor formation are rare. Although we do not know the exact mechanism of tumor genesis, we consider the fibroblast formation in the routine healing process to be a possible mechanism. Further investigation is necessary to identify coexisting factors that increase the risk of tumor formation after implantation. PMID- 22049962 TI - Medial and lateral segond fractures in a skeletally immature patient: a radiographic marker for the multiply injured knee. AB - Marginal fractures of the medial tibial plateau have been reported in the literature as a secondary type of Segond fracture. Some reports described this entity in the setting of combined injuries such as root avulsions of the medial meniscus, complete disruption of the posterior cruciate ligament (PCL), partial tear of the anterior cruciate ligament (ACL), and tears of the medial meniscus and medial collateral ligament. It has been postulated that medial marginal fractures are secondary to compression of the medial aspect of the femoral condyle and tibial plateau with a corresponding posterolateral corner injury. However, this mechanism of injury may not always be as straightforward.This article presents a case of an alternate injury pattern in a skeletally immature patient. A 16-year-old boy sustained a varus force and twisting injury to his knee, resulting in radiographic evidence of multiple avulsion fractures of the knee, including a fibular epiphyseal avulsion fracture and medial and lateral Segond fractures. Usually, the avulsion fractures serve as markers for significant ligamentous injuries in adult patients, but our patient had minimal injury to the PCL, ACL, and posterolateral corner. Further physical examination and imaging studies revealed an anterior horn root avulsion, meniscocapsular separation, and anterior cortical rim fracture. A combination of imaging modalities helped us further characterize the injury pattern to devise the optimal surgical plan, especially the fixation of the anterior cortical fracture of the tibia. PMID- 22049963 TI - Open glenohumeral dislocation: skeletonization of the proximal humerus without associated fracture. AB - Shoulder dislocations are common injuries. In the realm of high-energy trauma, enough force can be dissipated to violate the entire soft tissue envelope surrounding the shoulder girdle, generating an open injury. This article presents a case of a young man involved in a motorcycle accident in which he sustained an open glenohumeral dislocation with complete skeletonization of the proximal humerus. There were no associated fractures with his injury. Our patient underwent staged irrigation and debridement of his shoulder with delayed tendoligamentous reconstruction of the skeletonized proximal humerus. After reconstruction, he was immobilized for 3 weeks and then began a progressive shoulder rehabilitation protocol. He healed with no evidence of infection, residual instability, or avascular necrosis at his 4-month follow-up examination. At that point, he had regained functional use of his shoulder for activities of daily living and had no pain. His range of active motion was limited to 90 degrees of flexion and abduction, 0 degrees of external rotation, and internal rotation to the L4. He had complete resolution of a sensory and motor axillary neuropraxia that resulted from his initial injury. It was felt that the patient had potential for continued gains in range of motion and strength.Our patient is only the second description of an open glenohumeral dislocation with no associated fractures of the proximal humerus. This skeletonization of the proximal humerus represents a complex soft tissue injury that severely compromises the functional capacity of the shoulder. Understanding the nature of the injury and the involved structures and maintaining a sound treatment algorithm allow orthopedic surgeons to maximize the patient's functional outcome. PMID- 22049964 TI - Treatment of severe hand deformities caused by epidermolysis bullosa. AB - Little research has been done regarding the treatment of severe hand deformities caused by epidermolysis bullosa. A 14-year-old boy was diagnosed with congenital epidermolysis bullosa. He was treated in our hospital several times, but the pathogenetic condition worsened. On examination, both hands were clenched fists and had scar formation. Skin fusion was observed between the 5 fingers. Nails were absent and the thumb was in the fist. His fingers were short, and active and passive flexion and extension could not be performed. The right hand was treated first. After the adhesions were separated, we found that the 5 fingers were connected by dermis. After the dermis was separated and the hand was fixed in the extension position, there were small cutaneous deficiencies. The fingers were fixed in the functional position with Kirschner wires. The wound surface was covered with self-made aureomycin ointment gauze. After regular dressing changes for 6 weeks, the wound surface was completely healed. After 3 months of rehabilitation training, most hand function was recovered.Based on our findings in this case, when treating patients with epidermolysis bullosa, physicians must carefully observe whether enough dermis exists to avoid an unnecessary skin graft. We also found that the quality of skin used in skingrafting is questionable due to pathological changes in the skin. If there is enough dermis and the cutaneous deficiency is smaller after contracture release, the covering of drug dressings on the cutaneous deficiency is more conducive to the recovery of limb function and the reduction of damage to the donor sites. PMID- 22049965 TI - Intracapsular origin of the long head of the biceps tendon with glenoid avulsion of the glenohumeral ligaments. AB - An 18-year-old woman presented with a history of recurrent glenohumeral dislocations involving her right dominant shoulder. Physical examination suggested physiologic hyperlaxity and anterior instability. Magnetic resonance arthrography demonstrated an anomalous intracapsular origin of the long head of the biceps tendon (LHBT), with normal-appearing LHBT in the intertubercular groove. Diagnostic arthroscopy confirmed the absence of the LHBT attachment on the superior labrum. Instead, the LHBT originated from the capsule of the shoulder joint. Diagnostic arthroscopy also revealed glenoid avulsion of the glenohumeral ligaments (GAGL) lesion as a tear in the anterior-inferior capsule near its insertion on the glenoid and labrum. An arthroscopic anterior capsulolabral repair was performed with rotator interval closure by imbrication of superior and middle glenohumeral ligaments. A retrospective review of the magnetic resonance arthrogram identified irregularity and interposition of contrast between the capsule and the anterior-inferior labrum that was reproduced in the abduction-external rotation view corresponding with the GAGL lesion seen at arthroscopy. At 12 months postoperatively, the patient demonstrated full range of motion and no signs of instability. This case report helps to raise awareness about 2 rare shoulder lesions: the anomalous origin of LHBT and the GAGL lesion. Diagnosing such lesions on preoperative magnetic resonance imaging may aid in operative planning and avoid unexpected intraoperative findings. PMID- 22049966 TI - Lumbar diskal cyst containing intervertebral disk materials. AB - The diskal cyst is a relatively new clinical entity and develops clinical symptoms of a unilateral single nerve root lesion. Although many cases of diskal cyst have been reported, the pathogenesis of diskal cyst remains unclear, and several theories regarding the pathogenesis have been proposed. This article presents 2 cases of diskal cyst communicating with an adjacent herniated disk. Magnetic resonance imaging findings showed diskal cysts in the epidural space of the lumbar spine. Surgical resection was performed, and apparent connections between the corresponding disk and cysts were found. Histopathologic examinations of the cyst wall demonstrated cartilaginous tissue including nucleus pulposus and annulus fibrosis. These patient's symptoms improved remarkably postoperatively, and there was no recurrence of diskal cyst.The hypothesis supported by many authors is hemorrhage from the epidural venous plexus. Diskal cysts arise first from an underlying intervertebral disk injury that causes an annulus fibrosis fissure in the posterior intervertebral disk. Hemorrhage from the epidural venous plexus with a rich blood flow then occurs in the space between the peridural membrane and vertebral body. However, in our cases, we confirmed that the diskal cyst could have developed from the resorption process of an intervertebral disk herniation. Only 5 cases of diskal cyst demonstrating the presence of cartilaginous tissue in the cyst have been reported. Our 2 cases are rare and support the hypothesis of resorption of intervertebral disk herniation. PMID- 22049967 TI - Unusual case of isolated lunate fracture without ligamentous injury. AB - Fractures of the lunate are rare injuries that usually result from high-energy trauma and are typically associated with other carpal and ligamentous injuries. The incidence of lunate fractures has been cited as 0.5% to 6.5% of all carpal fractures. These fractures are not frequently reported in the literature, and no consensus exists on the treatment of these injuries in the acute and chronic setting. The mechanism typically producing this fracture is a loading force applied to a dorsiflexed, ulnarly deviated wrist such that the capitate is driven downward into the lunate.No prior reports exist in the literature of an isolated fracture of the lunate without perilunate dislocation or ligament disruption. This article reports a case of an isolated displaced transverse shear fracture of the lunate seen 3 months after initial injury, which was successfully treated using a volar and dorsal combined approach and open reduction and internal fixation using microscrews. Bony union across the fracture site was obtained by 7 week follow-up and continued to show improved consolidation through 10-month follow-up. The patient had decreased pain, normal range of motion, and no radiographic evidence of lunate osteonecrosis on most recent follow-up despite the delayed presentation and degree of fracture displacement. This case demonstrates a previously unreported type of wrist injury. PMID- 22049968 TI - Percutaneous vertebral body cement augmentation for back pain related to occult osteomyelitis/diskitis. AB - Although complications related to vertebroplasty or kyphoplasty are few, we treated 2 patients with vertebroplasty or kyphoplasty for pain, presumed to be due to vertebral compression fractures, which were subsequently found to be due to occult osteomyelitis/diskitis. The onset of their infections appeared to have preceded their vertebral body augmentation procedures and was possibly due to prior interventional procedures for histories of back pain.An 86-year-old woman had had 3 prior kyphoplasty procedures for fractures at T10, T11, and L1. She reported continued severe pain, and subsequent magnetic resonance imaging was misinterpreted for another fracture at T12, resulting in her fourth kyphoplasty. She became septic and had some improvement with antibiotics, but she declined specialty care and died. A 74-year-old man with chronic back pain had recently undergone lumbar facet joint injections. Computed tomography and subsequent bone scan found uptake at both L2 and L3. Despite abnormal erythrocyte sedimentation rate and C-reactive protein level and normal radiographic vertebral height, he underwent a vertebroplasty. His pain increased, and subsequent workup found L2-3 diskitis. He recovered with antibiotics and specialty care. Similar to prior reports of spondylodiskitis, both patients had multiple medical comorbidities.This article emphasizes the need for clinical reevaluation and scrutiny in the interpretation of imaging studies, including for infection in patients with continued pain after spinal procedures. The differential diagnosis of infectious etiology is an important consideration prior to vertebral cement augmentation for presumed fragility fracture. PMID- 22049969 TI - Giant gouty tophi of the hand and wrist. AB - Gout is an inflammatory-rheumatic disease characterized by an elevated serum urate concentration and recurrent flares, including painful, hot, red, and swollen joints and surrounding tissue. Untreated gout often develops into a chronic disease with tophi and destruction of joint surfaces. Giant tophi are often resistant to medication and change in diet.This article presents a case of a 44-year-old man with giant gouty tophi at his hand and wrist. The last acute gout flare in his left wrist was approximately 3 years prior. For 2 years he had refused adequate nutrition, such as a low-purine diet, and had refused to take any preventive medication. Blood urate level was elevated to 8.7 mg/dL (normal range, 3.4-7.0 mg/dL). In time, the tophi led to a massive limitation of motion and use of especially the left wrist and thumb. Under the condition that the patient changed his diet and took the medication for his underlying disease, we surgically removed the almost skin-perforating tophi. Surgical debulking significantly improved joint function and cosmetic appearance.The best treatment for gouty tophi is prevention by ensuring adequate nutrition, treating the underlying causes, and taking effective medication. In the case of massive limitation of joint motion, skin breakdown with risk of infection, and compression of neurovascular structures, surgical debulking of the tophi should be considered. PMID- 22049970 TI - Pyogenic cervical spondylitis caused by Pasteurella haemolytica attributed to excessive contact with dogs. AB - The bacterium Pasteurella haemolytica is resident in the oral cavities of dogs and cats and is often a cause of zoonotic infection. However, it is rare for it to be the pathogenic bacteria behind pyogenic spondylitis, and few studies have been conducted on it. This article reports a case of pyogenic cervical spondylitis thought to be caused by excessive contact with pet dogs.A 52-year-old man reported neck pain and pain in the right upper limb. He was admitted after plain radiographs and magnetic resonance imaging suggested pyogenic spondylitis. Pasteurella haemolytica was detected by needle aspiration biopsy of the intervertebral disk. Because the patient owned 2 dogs and frequently kissed them on the mouth, the cause of infection was thought to be excessive contact with pet dogs. Symptoms were alleviated with bed rest and administration of antibiotics with a higher sensitivity to this bacterium. PMID- 22049971 TI - Periostitis secondary to prolonged voriconazole therapy in a lung transplant recipient. AB - This article reports a case of perostitis deformans in a lung transplantation patient taking the fluoride-containing medication voriconazole, a relatively new and potent anti-fungal. The patient had a normal range of motion in all joints and a normal gait. On radiographs at presentation, multifocal areas of periostitis were visualized involving the left-hand first, second, and third proximal phalanx shafts. Similar periostitis was present on the left-hand third, fourth, and fifth middle phalanx shafts. Plain radiographs of the right hand also demonstrated multifocal periostitis of the third and fourth proximal and middle phalanges. Aggressive periostitis at the level of the right fourth proximal and middle phalanges was also present. Given her long-term treatment with voriconazole and a presentation consistent with periostitis deformans, voriconazole was presumed to be the offending agent and was replaced with itraconazole. The patient's symptoms resolved shortly after withdrawal of voriconazole.Voriconazole-associated periostitis has only recently been reported in the literature. Food and Drug Administration-approved in 2002, voriconazole is efficacious in treating serious, invasive fungal infections that are generally seen in immunocompromised patients. Due to the novel nature of voriconazole and the uncommon indications for its long-term use, the periostitis deformans described in this article may be unfamiliar to the orthopedic surgeon. Consequently, a patient presenting with bone pain and periosteal involvement on plain radiographs may provoke a broad, expensive, and ultimately unnecessary diagnostic evaluation. The clinical case and imaging findings presented here can help to promote understanding of this benign condition and its simple cure: voriconazole discontinuation. PMID- 22049972 TI - Digital flexion contracture and severe carpal tunnel syndrome due to tophaceus infiltration of wrist flexor tendon: first manifestation of gout. AB - The authors report an unusual case of flexor tenosynovitis, severe carpal tunnel syndrome, and triggering at the carpal tunnel as the first manifestation of gout. A 69-year-old man presented with digital flexion contracture and severe carpal tunnel syndrome of his right hand and was treated surgically. A flexor tenosynovectomy and a median nerve neurolysis were performed through an extended carpal tunnel approach. The sublimis and the profundus tendons were involved. Partial ruptures and multiple whitish lesions suggestive of tophacceous infiltration of the flexor tendons were seen. Macroscopically, the removed synovial tissue was involved by multiple whitish nodules that were milimetric in size and was suggestive of monosodium urate crystals deposits. By light microscopy examination, numerous nonnecrotizing granulomas of different sizes were observed that were compounded by large aggregations of acellular nonpolarized material, surrounded by epithelioid histiocytes, mononuclear cells, and foreign body multinucleated giant cells. Postoperatively, the patient recovered with resolution of the median nerve symptoms and a near-to-full range of motion of the affected digits.To the authors' knowledge, this patient is the first case report with flexor tendons tophacceous infiltration as the first clinical sign of gout. Gouty flexor tenosynovitis can occur in the absence of a long history of gout. A high index of suspicion is paramount to the initiation of proper management. Operative treatment of gouty flexor tenosynovitis is mandatory to debulk tophaceous deposits, improve tendon gliding, and decompress nerves. Routine uric acid determination could be helpful in the preoperative evaluation of patients with flexor tenosynovitis. PMID- 22049973 TI - Cholesteryl butyrate solid lipid nanoparticles inhibit the adhesion and migration of colon cancer cells. AB - BACKGROUND AND PURPOSE Cholesteryl butyrate solid lipid nanoparticles (cholbut SLN) provide a delivery system for the anti-cancer drug butyrate. These SLN inhibit the adhesion of polymorphonuclear cells to the endothelium and may act as anti-inflammatory agents. As cancer cell adhesion to endothelium is crucial for metastasis dissemination, here we have evaluated the effect of cholbut SLN on adhesion and migration of cancer cells. EXPERIMENTAL APPROACH Cholbut SLN was incubated with a number of cancer cell lines or human umbilical vein endothelial cells (HUVEC) and adhesion was quantified by a computerized micro-imaging system. Migration was detected by the scratch 'wound-healing' assay and the Boyden chamber invasion assay. Expression of ERK and p38 MAPK was analysed by Western blot. Expression of the mRNA for E-cadherin and claudin-1 was measured by RT-PCR. KEY RESULTS Cholbut SLN inhibited HUVEC adhesiveness to cancer cell lines derived from human colon-rectum, breast, prostate cancers and melanoma. The effect was concentration and time-dependent and exerted on both cancer cells and HUVEC. Moreover, these SLN inhibited migration of cancer cells and substantially down modulated ERK and p38 phosphorylation. The anti-adhesive effect was additive to that induced by the triggering of B7h, which is another stimulus inhibiting both ERK and p38 phosphorylation, and cell adhesiveness. Furthermore, cholbut SLN induced E-cadherin and inhibited claudin-1 expression in HUVEC. CONCLUSION AND IMPLICATIONS These results suggest that cholbut SLN could act as an anti metastastic agent and they add a new mechanism to the anti-tumour activity of this multifaceted preparation of butyrate. PMID- 22049974 TI - Management of cirrhotic patients with hepatocellular carcinoma treated with sorafenib. AB - Sorafenib (Nexavar(r), Bayer), a multi-targeted tyrosine kinase inhibitor, was the first systemic agent that demonstrated a significant improvement in the overall survival in patients with advanced hepatocellular carcinoma and well preserved liver function. This drug is now recommended in patients with advanced hepatocellular carcinoma as first-line therapy and for patients not suitable for locoregional treatment. This brief article, produced by a multidisciplinary panel including specialists in gastroenterology and oncology, provides an overview of the major issues related to systemic treatment of hepatocellular carcinoma with sorafenib, including staging and prognostic strategies, assessment of liver disease and its complications, and efficacy and safety of this molecule. Particular emphasis is given on how to improve tolerability of sorafenib in difficult-to-treat patients. PMID- 22049975 TI - Interdisciplinary approach towards female patients with Fabry disease. AB - BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder leading to an accumulation of globotriaosylceramides in the lysosomes of various organs. DESIGN: Being X-chromosomal-linked, most studies in the past have focused on involvement in male patients. However, it has been elucidated recently that female patients can present typical organ involvement and thus need to be treated, respectively. CONCLUSIONS: This review wants to give a systematical overview of the typical organ involvement in female patients with FD. Moreover, therapy recommendations especially for female patients are discussed. PMID- 22049976 TI - The right ventricular septum presents the optimum site for maximal electrical separation during left ventricular pacing. AB - Cardiac resynchronization therapy (CRT) benefits selected heart failure (HF) patients. The optimal placement of the right ventricle (RV) lead during biventricular pacing has not been assessed. Greater electrical separation (ES) between left ventricle (LV) and RV leads has been associated with better clinical outcomes. The site of maximal electrical separation(MES) in the RV is unknown. METHODS: Prospective study of 50 CRT patients. The LV lead was placed in a postero-lateral branch of the coronary sinus. ES was recorded at 6 sites within the RV during LV pacing at 600 milliseconds cycle length (CL). The median ES was recorded with a roving deflectable catheter at the RV outflow tract (RVOT), high septum, inflow septum, mid-septum, apical septum and apex. RESULTS: Mean age was 67 +/- 7 years, 39 were male (78%). Thirty had ischemic etiology (60%). Mean left ventricular ejection fraction (LVEF) was 25 +/- 7%, QRS duration pre and post was 165 +/- 26 milliseconds and 138.5 +/- 15.6 milliseconds (P < 0.001). Mapping ES showed a difference between 20 and 50 milliseconds distributed across the RV in the majority of patients (40/49). However, 7 subjects demonstrated delay distribution of between 50 and 82 milliseconds. ES was significant greater in the RV mid-septum (161.2 +/- 23.7 milliseconds) compared with RVOT (154.1 +/- 20.8 milliseconds) and apex (148.0 +/- 25.5 milliseconds; P < 0.001). The site of Maximal ES was most commonly found at the mid-septum (40 patients, 80%) and only rarely at the RVOT (5, 10%) and apex (5, 10%; P < 0.01). CONCLUSION: MES was observed most commonly at the RV septum and rarely at the RV apex. Better correction of electrical and mechanical dyssynchrony by CRT may be achieved by placing the RV lead in a site outside of the apex in the majority of patients. Clinical studies exploring RV septal pacing in CRT seem warranted. PMID- 22049977 TI - New evidence for toxicity of polybrominated diphenyl ethers: DNA adduct formation from quinone metabolites. AB - This study investigated the formation of DNA adducts of polybrominated diphenyl ethers (PBDEs) and the possible mechanisms. DNA adduction was conducted by in vitro reaction of deoxyguanosine (dG) and DNA with PBDE-quinone (PBDE-Q) metabolites, and DNA adducts were characterized by using electrospray ionization tandem mass spectrometry. The results suggested DNA adduction involved Michael Addition between the exocyclic NH(2) group at the N-2 position of dG and the electron-deficient carbon of quinone, followed by reductive cyclization with loss of (bromo-)1-hydroperoxy-benzene or water to form a type I or type II adduct. PBDE-Q with substituted bromine on the quinone ring was proven to be a favorable structure to form a type I adduct, while the absence of bromine on the quinone ring resulted in a type II adduct. Lower reactivity of adduction was also observed with increasing the number of bromine atoms on the phenoxyl ring. Our data clearly demonstrated PBDEs could covalently bind to DNA mediated by quinone metabolites, depending on the degree of bromine substitution. This study opened a new view on the mechanism of toxicity of PBDEs and reported the structure of PBDE DNA adducts, which might be valuable for the evaluation on potential in vivo formation of PBDE-DNA adducts. PMID- 22049978 TI - Is quantity more important than quality? PMID- 22049979 TI - A truly integrated treatment system must be both patient- and process-focused. PMID- 22049980 TI - Innovative policy strategies need empirical evaluation. PMID- 22049981 TI - Market forces do not solve the problems. PMID- 22049982 TI - Commentary on Vangeli et al. (2011): Towards an improved understanding of smoking relapse predictors--recipe for success? PMID- 22049983 TI - Commentary on Andreuccetti et al. (2011): The gap between stricter blood alcohol concentration legislation and enforcement in Brazil. PMID- 22049984 TI - Commentary on Bodin & Strandberg (2011): Scepticism, publication bias and a grain of salt--do we already know how to evaluate prevention programmes? PMID- 22049985 TI - Commentary on Gibson et al. (2011): Brief alcohol interventions in the context of treatment for hepatitis C. PMID- 22049986 TI - Real-time PCR method applied to seafood products for authentication of European sole (Solea solea) and differentiation of common substitute species. AB - Judged by quality and taste, the European sole (Solea solea) is considered one of the finest flatfish and is, thus, of considerable commercial value. In the present work, a specific fast real-time PCR was developed for the authentication of S. solea, i.e. to distinguish it from other related species and avoid substitution of this species, either deliberately or unintentionally. The method is based on a species-specific set of primers and MGB Taqman probe which amplifies a 116-bp fragment of the internal transcribed spacer 1 (ITS 1) ribosomal DNA region. This assay combines the high specificity and sensitivity of real-time PCR with the rapidity of the fast mode, allowing the detection of S. solea in a short period of time. The present methodology was validated for application to all types of manufactured products for the presence of S. solea, with successful results. Subsequently, the method was applied to 40 commercial samples to determine whether correct labeling had been employed in the market. It was demonstrated that the assay is a useful tool in monitoring and verifying food labeling regulations. PMID- 22049987 TI - Some alternatives to asymptotic tests for the analysis of pharmacogenetic data using nonlinear mixed effects models. AB - Nonlinear mixed effects models allow investigating individual differences in drug concentration profiles (pharmacokinetics) and responses. Pharmacogenetics focuses on the genetic component of this variability. Two tests often used to detect a gene effect on a pharmacokinetic parameter are (1) the Wald test, assessing whether estimates for the gene effect are significantly different from 0 and (2) the likelihood ratio test comparing models with and without the genetic effect. Because those asymptotic tests show inflated type I error on small sample size and/or with unevenly distributed genotypes, we develop two alternatives and evaluate them by means of a simulation study. First, we assess the performance of the permutation test using the Wald and the likelihood ratio statistics. Second, for the Wald test we propose the use of the F-distribution with four different values for the denominator degrees of freedom. We also explore the influence of the estimation algorithm using both the first-order conditional estimation with interaction linearization-based algorithm and the stochastic approximation expectation maximization algorithm. We apply these methods to the analysis of the pharmacogenetics of indinavir in HIV patients recruited in the COPHAR2-ANRS 111 trial. Results of the simulation study show that the permutation test seems appropriate but at the cost of an additional computational burden. One of the four F-distribution-based approaches provides a correct type I error estimate for the Wald test and should be further investigated. PMID- 22049988 TI - Analytical measurements of atmospheric urban aerosol. AB - Understanding the complex nature of atmospheric urban aerosol mandates the utilization of analytical technology. In this feature article, we provide a glimpse of several analytical techniques that are most commonly used for urban atmospheric aerosol measurements, with an emphasis on particle mass spectrometry methods. PMID- 22049989 TI - Diversified nanoparticle assembly pathways: materials architecture control beyond the amphiphilicity paradigm. AB - The functional versatility of a chemical system is ultimately dictated by the availability of distinctly accessible architectures. The generation of a diverse array of assembled constructs from a single type of nanoscale building block is a promising yet largely elusive goal. We report herein the utility of a monolayer modified nanoparticle for the creation of a broad range of architectures. The versatile modes of assembly complement the conventionally used, amphiphilicity driven strategy. We demonstrate that one can vary the nanoparticle assembly pathways within the confines of solvent media through the modulation of interactions and partitioning of nanoparticles. Merging of the molecular-scale design and higher-ordered arrangement enables diversified assembly through the manipulation of experimental parameters such as solvent, pH, affinity molecule, and temperature. Microfluidics provides an effective channel to control the monodispersity and size on all the architectures attainable in the bulk solution phase. These observations could be further explored for an understanding of diversified matter organization and order generation beyond the amphiphilicity paradigm. PMID- 22049990 TI - Antifungal susceptibility patterns of yeasts and filamentous fungi isolated from nail infection. AB - BACKGROUND: Onychomycosis is the nail infection caused by a wide spectrum of fungi species, including yeasts, dermatophytes and filamentous fungi non dermatophytes (FFND). This fungal infection represents an important medical problem because it involves the patient's life quality. OBJECTIVE: The aim was to isolate and identify the fungal agents of onychomycosis, and to determine the in vitro susceptibility to antifungal agents. METHODS: During the period of March 2008 to March 2009, 114 patients clinically suspected of having onychomycosis were examined. Demographic data, mainly age and gender were obtained from each patient. The nail samples collected (136) were submitted to direct examination with potassium hydroxide 20% and grown on Sabouraud dextrose agar. The in vitro antifungal susceptibility testing was performed according to the method of broth microdilution, recommended by the Clinical Laboratory Standards Institute (CLSI). RESULTS: Onychomycosis was observed in 95 (83.3%) patients, including 16 men (16.8%) and 79 women (83.2%), with mean age of 48.1 years. Candida parapsilosis, Trichophyton rubrum and Fusarium spp were the fungi most frequently isolated. The most of the isolated yeasts showed susceptibility to antifungal agents studied. Among filamentous fungi, high MIC values to itraconazole were found for T. rubrum and T. mentagrophytes, while Fusarium spp showed decreased susceptibility to itraconazole and voriconazole. CONCLUSION: C. parapsilosis was the most common fungal species isolated from patients with onychomycosis. The different response obtained by in vitro susceptibility testing to drugs shows the importance of these methods to assist clinicians in choosing the best therapeutic option. PMID- 22049991 TI - Zinc sulphate: a new concept of treatment of erythropoietic protoporphyria. PMID- 22049992 TI - Improvement in water stability and other related functional properties of thin cast kafirin protein films. AB - Improvement in the water stability and other related functional properties of thin (<50 MUm) kafirin protein films was investigated. Thin conventional kafirin films and kafirin microparticle films were prepared by casting in acetic acid solution. Thin kafirin films cast from microparticles were more stable in water than conventional cast kafirin films. Treatment of kafirin microparticles with heat and transglutaminase resulted in slightly thicker films with reduced tensile strength. In contrast, glutaraldehyde treatment resulted in up to a 43% increase in film tensile strength. The films prepared from microparticles treated with glutaraldehyde were quite stable in ambient temperature water, despite the loss of plasticizer. This was probably due to the formation of covalent cross-linking between free amino groups of the kafirin polypeptides and carbonyl groups of the aldehyde. Thus, such thin glutaraldehyde-treated kafirin microparticle films appear to have good potential for use as biomaterials in aqueous applications. PMID- 22049993 TI - Spin relaxation in InGaN quantum disks in GaN nanowires. AB - The spin relaxation time of photoinduced conduction electrons has been measured in InGaN quantum disks in GaN nanowires as a function of temperature and In composition in the disks. The relaxation times are of the order of ~100 ps at 300 K and are weakly dependent on temperature. Theoretical considerations show that the Elliott-Yafet scattering mechanism is essentially absent in these materials and the results are interpreted in terms of the D'yakonov-Perel' relaxation mechanism in the presence of Rashba spin-orbit coupling of the wurtzite structure. The calculated spin relaxation times are in good agreement with the measured values. PMID- 22049994 TI - Isolation of human mAbs that directly modulate FMS-related tyrosine kinase 3 signaling. AB - FMS-related tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase that plays important roles in hematopoiesis, including early progenitors and dendritic cell development. FLT3 is expressed at high levels in 70-100% of cases of AML and in virtually all cases of B-lineage acute lymphoblastic leukemia. FLT3 is regarded as a molecular target in the development of novel therapies for acute leukemia patients. Currently, many small-molecule FLT3 inhibitors have been developed, but clinical trials have resulted in limited antileukemia effects because of off-target toxicities and drug resistance. The development of anti FLT3 Abs might overcome these difficulties and enhance the antileukemia efficacy of FLT3 inhibitors. In the present study, we demonstrate the isolation of novel human mAbs against FLT3 with antagonistic or agonistic activities. An antagonistic Ab, designated A2, continuously inhibits FLT3 ligand (FL)-induced phosphorylation of FLT3 and MAPK. A2 cooperatively induces apoptosis with daunorubicin, even in the presence of FL. An agonistic Ab, designated 3E6, surprisingly induces the phosphorylation of FLT3 and MAPK, and supports the growth of a factor-dependent cell line independently of FL addition. In addition, A2 showed complement-dependent cytotoxicity activity, but was devoid of Ab dependent cell mediated cytotoxicity. Finally, we evaluated Ab internalization in a cell line. Immunofluorescence and flow cytometry analyses revealed that A2 is efficiently internalized. Collectively, these data demonstrate that A2 is a potent human Ab that might be capable of delivering cytotoxic reagents and that has antagonistic effects on FLT3 signaling. In addition, 3E6 might be a potential scaffold for novel dendritic cell-based immunotherapies. PMID- 22049996 TI - Polymorphism in morels: isozyme electrophoretic analysis. AB - The aim of this study was to assess whether isozyme polymorphism in different members of the Morchellaceae could be used to improve the systematics in this fungal group and to characterize intraspecific crossings between monosporal strains in Morchella esculenta. For this purpose, isozyme electrophoretic analysis of the following enzymes was performed: glutamine synthetase, NAD glutamate dehydrogenase, NADP-glutamate dehydrogenase, aspartate aminotransferase, malate dehydrogenase, NAD-glyceraldehyde phosphate dehydrogenase, glucose phosphate isomerase, and superoxide dismutase. The analyses allowed discrimination at the inter- or intra-specific levels and could help to establish a method of identification for strains in the Morchellaceae. To a certain extent they appeared to be suitable to analyze interactions of monosporal strains of Morchella esculenta in pairing experiments. The polymorphism shown in this study was consistent with the phylogenetic relationships between the investigated strains only at the genus level.Key words: isozyme analysis, electrophoresis, Morchella sp., polymorphism. PMID- 22049995 TI - Level of agreement between self-administered and interviewer-administered CPQ8-10 and CPQ1-14. AB - OBJECTIVES: The aim of the present study was to assess the psychometric properties and level of agreement between the self-administered and interviewer administered Child Perceptions Questionnaire (CPQ) for children between 8 and 10 years of age (CPQ(8-10) ) and between 11 and 14 (CPQ(11-14) ) years of age. METHODS: A randomized cross-over study was carried out, involving 180 children (Group 1 - 90 children between 8 and 10; Group 2 - 90 children between 11 and 14 years of age) in the state of Minas Gerais, Brazil. All children completed both administration modes of the CPQ; half of each group received interviewer administered mode first [Subgroup A (CPQ(8-10) n = 45) and Subgroup C (CPQ(11-14) n = 45)], and the other half performed the self-administered mode first [Subgroup B (CPQ(8-10) n = 45) and Subgroup D (CPQ(11-14) n = 45)]. Test-retest reliability of each mode of administration was tested on 60 children (30 for CPQ(8-10) ; 30 for CPQ(11-14) ), who were not included in the other analyses. The level of agreement between scores on the self-administered and interviewer-administered versions of the CPQ(8-10) and CPQ(11-14) was established using the intraclass correlation coefficient (ICC). The order of presentation of both instruments was tested considering the four subgroups (A, B, C and D). The calculation of effect size proposed by Cohen (1992) was used to test the clinical significance of the findings. RESULTS: Both the self-administered and interviewer-administered versions of CPQ(8-10) and CPQ(11-14) demonstrated acceptable psychometric properties. Agreement between the administration modes for the CPQ(8-10) and CPQ(11-14) was 0.90 and 0.88 (ICC), respectively. With the exception of the functional limitation subscale, the scores of the subscales and overall score on the CPQ(8-10) were significantly higher in the group of children who responded to the interviewer-administered measure first. With the CPQ(11-14) , statistically significant differences were found only for the emotional well-being subscale. CONCLUSIONS: Both administration modes of the CPQ(8-10) and CPQ(11-14) demonstrated satisfactory psychometric properties and a high level of agreement. Although statistically significant differences were observed for oral symptoms, emotional well-being and social well-being, with the first administration of the interviewer-administered version, the effect of the order of administration had small to medium effects on the CPQ scores. PMID- 22049997 TI - Biosynthesis of the trichothecene 3-acetyldeoxynivalenol: cell-free hydroxylations of isotrichodermin. AB - 3-Acetyldeoxynivalenol is the major trichothecene produced by the fungus Fusarium culmorum. Studies in vivo with F. culmorum have established the following biosynthetic precursors of 3-acetyldeoxynivalenol: isotrichool -> isotrichodiol > isotrichodermin -> 15-deacetylcalonectrin, 7alpha-hydroxyisotrichodermin, 8alpha-hydroxyisotrichodermin -> calonectrin -> deoxynivalenol. In this paper, we describe in vitro investigations of one of these metabolic steps. The cell-free system of F. culmorum that converts isotrichodermin into 15-deacetylcalonectrin, 7alpha-hydroxyisotrichodermin, and 8alpha-hydroxyisotrichodermin is described here. This preparation requires NADPH but not NADH for activity and is not inhibited by carbon monoxide, cyanide, or known oxygenase inhibitors, such as SKF 525-A or ancymidol.Key words: trichothecene, Fusarium culmorum, cell-free system, isotrichodermin, 15-deacetylcalonectrin. PMID- 22049998 TI - Preference in the nodulation of Phaseolus vulgaris cv. RAB39. II. Effect of delayed inoculation or low cell representation in the inoculant on nodule occupancy by Rhizobium tropici UMR1899. AB - Common bean (Phaseolus vulgaris L.) is a traditional crop in much of Latin America, where it is often planted into soils containing numerous, sometimes ineffective, indigenous rhizobia. The presence of these indigenous organisms can limit response to inoculation. Because of this, we have sought bean cultivars that will nodulate preferentially with the inoculant strain, and have previously reported on the preference between the bean cultivar RAB39 and strains of Rhizobium tropici. We have detailed this interaction using the inoculant-quality strain UMR1899. In the present study the root tip marking (RTM) technique was used to demonstrate that this preference in nodulation was evident, even when inoculation with UMR1899 was delayed up to 8 relative to that with Rhizobium etli UMR1632. In contrast to studies with other legumes, roots of RAB39 were not predisposed to nodulate with UMR1632, even though preexposed to this strain for considerable periods of time. The presence of UMR1899 actually reduced nodulation by UMR1632 substantially, even when inoculation with UMR1899 was significantly delayed. When UMR1899 and UMR1632 were applied to separate halves of a split-root system, the number of nodules on the side receiving UMR1632 was less than for the half root inoculated with UMR1899, but the differences were not significant. This suggests that the preference response is not systemic but requires proximity between the strains involved. UMR1899 produced more than 50% of the nodules even when the ratio of UMR1632:UMR1899 in the inoculant was 10:1. The results are further evidence of a stable and marked preference of RAB39 for UMR1899, which warrants a more detailed study at the field level.Key words: Phaseolus vulgaris L., common bean, delayed inoculation, strain preference, cell proportions. PMID- 22049999 TI - Microbial transformation of 3,4-methylenedioxy-N-methylamphetamine and 3,4 methylenedioxyamphetamine. AB - The biotransformation of 3,4-methylenedioxy-N-methylarnphetamine (MDMA) and 3,4 methylenedioxyamphetamine (MDA) was examined in the fungus Cunninghamella echinulata. In addition to the reported mammalian metabolites (MDA, 3,4 methylenedioxybenzyl methyl ketoxime, 3,4-methylenedioxybenzyl methyl ketone) and the parent substrate, there were six novel metabolites detected. N-Acetyl-3,4 methylenedioxyamphetamine (NAcMDA) was unequivocally identified and three unidentified metabolites related to NAcMDA were also detected. N-Acetyl-3,4 methylenedioxy-1-phenyl-1-hydroxy-2-aminopropane was tentatively identified as a metabolite of MDMA. The only metabolite of MDA identified was NAcMDA. Two metabolites related to MDA remain unidentified.Key words: Cunninghamella, amphetamine, biotransformation, 3,4-methylenedioxy-N-methylamphetamine, 3,4 methylenedioxyamphetamine. PMID- 22050002 TI - Operative Dentistry Home Page. PMID- 22050000 TI - Oxidation and amidation of salicylate by Streptomyces species. AB - Seven streptomycete strains were tested for biotransformation of salicylate. The products were identified by nuclear magnetic resonance spectroscopy and three types of conversion were found. Streptomyces cinnamonensis and Streptomyces spectabilis formed gentisate and salicylamide concurrently. Streptomyces rimosus transformed salicylate to salicylamide. Streptomyces lividans, Streptomyces coelicolor, Streptomyces griseus and Streptomyces avermitilis produced only gentisate. Time course studies of salicylate conversion by thin-layer chromatography and high pressure liquid chromatography showed that salicylamide was accumulated in the culture broth, whereas gentisate was further metabolized.Key words: salicylate, gentisate, salicylamide, biotransformation, Streptomyces spp. PMID- 22050003 TI - Erratum. PMID- 22050004 TI - Hydrothermal carbon from biomass: structural differences between hydrothermal and pyrolyzed carbons via 13C solid state NMR. AB - The objective of this paper is to better describe the structure of the hydrothermal carbon (HTC) process and put it in relationship with the more classical pyrolytic carbons. Indeed, despite the low energetic impact and the number of applications described so far for HTC, very little is known about the structure, reaction mechanism, and the way these materials relate to coals. Are HTC and calcination processes equivalent? Are the structures of the processed materials related to each other in any way? Which is the extent of polyaromatic hydrocarbons (PAH) inside HTC? In this work, the effect of hydrothermal treatment and pyrolysis are compared on glucose, a good model carbohydrate; a detailed single-quantum double-quantum (SQ-DQ) solid state (13)C NMR study of the HTC and calcined HTC is used to interpret the spectral region corresponding to the signal of furanic and arene groups. These data are compared to the spectroscopic signatures of calcined glucose, starch, and xylose. A semiquantitative analysis of the (13)C NMR spectra provides an estimation of the furanic-to-arene ratio which varies from 1:1 to 4:1 according to the processing conditions and carbohydrate employed. In addition, we formulate some hypothesis, validated by DFT (density functional theory) modeling associated with (13)C NMR chemical shifts calculations, about the possible furan-rich structural intermediates that occur in the coalification process leading to condensed polyaromatic structures. In combination with a broad parallel study on the HTC processing conditions effect on glucose, cellulose, and raw biomass (Falco, C.; Baccile, N.; Titirici, M.-M. Green Chem., 2011, DOI: 10.1039/C1GC15742F), we propose a broad reaction scheme and in which we show that, through HTC, it is possible to tune the furan to-arene ratio composing the aromatic core of the produced HTC carbons, which is not possible if calcination is used alone, in the temperature range below 350 degrees C. PMID- 22050005 TI - The effect of sonority on word segmentation: evidence for the use of a phonological universal. AB - It has been well documented how language-specific cues may be used for word segmentation. Here, we investigate what role a language-independent phonological universal, the sonority sequencing principle (SSP), may also play. Participants were presented with an unsegmented speech stream with non-English word onsets that juxtaposed adherence to the SSP with transitional probabilities. Participants favored using the SSP in assessing word-hood, suggesting that the SSP represents a potentially powerful cue for word segmentation. To ensure the SSP influenced the segmentation process (i.e., during learning), we presented two additional groups of participants with either (a) no exposure to the stimuli prior to testing or (b) the same stimuli with pauses marking word breaks. The SSP did not influence test performance in either case, suggesting that the SSP is important for word segmentation during the learning process itself. Moreover, the fact that SSP-independent segmentation of the stimulus occurred (in the latter control condition) suggests that universals are best understood as biases rather than immutable constraints on learning. PMID- 22050006 TI - Biological efficacy and stability of diluted ticarcillin-clavulanic acid in the topical treatment of Pseudomonas aeruginosa infections. AB - Topical compounded Timentin((r)) diluted with an inactive vehicle has been reported to be effective in the treatment of otitis externa caused by Pseudomonas aeruginosa. The aims of this study were to determine the biological efficacy of Timentin((r)) (ticarcillin and clavulanic acid) when diluted in the carrier vehicle Methopt((r)) against P. aeruginosa and to determine the efficacy and stability of Timentin((r)) aqueous stock concentrate solution. Timentin((r)) stock concentrate was tested against four P. aeruginosa isolates on days 0, 7, 14, 21 and 28; then after 2, 3, 4, 5, 6, 9 and 12 months of storage at 4 or -20 degrees C. The diluted Timentin((r))-Methopt((r)) solutions were tested against all isolates after 0, 2, 4, 6, 8, 10, 12, 14, 17, 21, 24 and 28 days of storage at 24 or 4 degrees C. Minimal inhibitory concentration (MIC) levels for all strains were determined using the broth microdilution method. The MIC of the stock solution remained relatively constant and acceptable throughout the study when stored at -20 degrees C and was also acceptable for shorter time periods (6 9 months) when stored at 4 degrees C. The MIC for the diluted Timentin((r)) Methopt((r)) solution remained relatively constant and acceptable throughout the study for all four bacterial strains, with no difference between the solutions stored at 4 or 24 degrees C. The results of this study indicate that storage of the Timentin((r)) stock solution at -20 degrees C does not compromise efficacy for at least 12 months and that Timentin((r)) diluted in Methopt((r)) was stable for 28 days when stored at either 4 or 24 degrees C. PMID- 22050007 TI - Robust and responsive silk ionomer microcapsules. AB - We demonstrate the assembly of extremely robust and pH-responsive thin shell LbL microcapsules from silk fibroin counterparts modified with poly(lysine) and poly(glutamic) acid, which are based on biocompatible silk ionomer materials in contrast with usually exploited synthetic polyelectrolytes. The microcapsules are extremely stable in an unusually wide pH range from 1.5 to 12.0 and show a remarkable degree of reversible swelling/deswelling response in dimensions, as exposed to extreme acidic and basic conditions. These changes are accompanied by reversible variations in shell permeability that can be utilized for pH controlled loading and unloading of large macromolecules. Finally, we confirmed that these shells can be utilized to encapsulate yeast cells with a viability rate much higher than that for traditional synthetic polyelectrolytes. PMID- 22050008 TI - Role of ion channels in sepsis-induced atrial tachyarrhythmias in guinea pigs. AB - BACKGROUND AND PURPOSE: Supraventricular tachyarrhythmias, including atrial fibrillation, are occasionally observed in patients suffering from sepsis. Modulation of cardiac ion channel function and expression by sepsis may have a role in the genesis of tachyarrhythmias. EXPERIMENTAL APPROACH: Sepsis was induced by LPS (i.p.; 300 ug.kg(-1) ) in guinea pigs. Membrane potentials and ionic currents were measured in atrial myocytes isolated from guinea pigs 10 h after LPS, using whole cell patch-clamp methods. KEY RESULTS: In atrial cells from LPS-treated animals, action potential duration (APD) was significantly shortened. It was associated with a reduced L-type Ca(2+) current and an increased delayed rectifier K(+) current. These electrophysiological changes were eliminated when N(G) -nitro-l-arginine methyl ester (l-NAME) or S ethylisothiourea was given together with LPS. In atrial tissues from LPS-treated animals, Ca(2+) channel subunits (Ca(v) 1.2 and Ca(v) 1.3) decreased and delayed rectifier K(+) channel subunits (K(v) 11.1 and K(v) 7.1) increased. However, L NAME treatment did not substantially reverse such changes in atrial expression in LPS-treated animals, with the exception that K(v) 11.1 subunits returned to control levels. After LPS injection, inducible NOS in atrial tissues was up regulated, and atrial NO production clearly increased. CONCLUSIONS AND IMPLICATIONS: In atrial myocytes from guinea pigs with sepsis, APD was significantly shortened. This may reflect nitration of the ion channels which would alter channel functions, rather than changes in atrial expression of the channels. Shortening of APD could serve as one of the mechanisms underlying atrial tachyarrhythmia in sepsis. PMID- 22050009 TI - Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation. AB - BACKGROUND: Cytochrome P450 inhibition by proton pump inhibitors (PPIs) may attenuate the effectiveness of clopidogrel. AIM: To examine whether PPI use modifies the association between clopidogrel use and major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) with stent implantation, using time-varying drug exposure ascertainment. METHODS: We conducted this population-based cohort study in Western Denmark (population 3 million) using medical databases. We identified all 13,001 patients with coronary stent implantation between 2002 and 2005 and ascertained their reported comorbidities. During the recommended 12-month postintervention treatment period, we tracked use of clopidogrel and PPI and the rate of MACE. We used Cox regression to compute hazard ratios (HRs), controlling for potential confounders. RESULTS: During follow-up, one or more prescriptions were redeemed by 91% of patients for clopidogrel and by 21% of patients for PPIs. Of the patients, 15% experienced a MACE. The adjusted HR for MACE comparing clopidogrel use with non use was 0.57 [95% confidence interval (CI): 0.44-0.74] among PPI users and 0.47 (95% CI: 0.42-0.53) among PPI non-users, yielding an interaction effect (i.e. relative rate increase) of 1.20 (95% CI: 0.91-1.58). PPI users treated from before PCI had a 25% increased rate of MACE compared to PPI non-users, independent of clopidogrel use [adjusted HR = 1.24 (95% CI: 0.97-1.58) for clopidogrel users and 1.26 (95% CI: 0.97-1.63) for clopidogrel non-users]. CONCLUSIONS: The use of PPIs as a class did not modify the protective effect of clopidogrel, but its use was associated with major adverse cardiovascular events itself, particularly among patients having used PPIs before percutaneous coronary intervention. PMID- 22050010 TI - Psychotherapy and psychopharmacology for mental health in adolescents with cancer: what integration is possible? PMID- 22050012 TI - Targeted therapies used sequentially in metastatic renal cell cancer: overall results from a large experience. AB - Targeted therapies have improved survival in patients with metastatic renal cell cancer (RCC); however, expert opinion on the optimal therapeutic strategy is divided. This retrospective study evaluates different sequential schemes of targeted therapies in 310 patients with advanced/metastatic RCC who received different systemic agents - sorafenib, sunitinib, bevacizumab, everolimus, temsirolimus and axitinib - alone or in different sequences, until disease progression or intolerable toxicity (median follow-up: 37 months). The median overall survival (OS) was 22 months and the 5-year OS was 23.4%; differential therapeutic schemes were not associated with differences in OS. A worse performance status, no nephrectomy and a poor-risk classification according to the Motzer criteria was associated with a shorter OS. These findings support the use of targeted therapies in the treatment of RCC, even in a large unselected population from a single institution, and suggest that treatment should be tailored to meet individual circumstances and needs. PMID- 22050013 TI - Role of fulvestrant in the management of postmenopausal breast cancer. AB - Fulvestrant is a form of endocrine therapy used in the treatment of postmenopausal breast cancer. It has a unique mechanism of action in that it causes the degradation of estrogen receptor and therefore has been labeled a selective estrogen receptor downregulator. Unlike the selective estrogen receptor modulator tamoxifen, it has no agonistic properties and is therefore a pure anti estrogen. Given its low level of bioavailability and presystemic metabolism, it has been formulated as an intramuscular injection. A number of dosing regimens have been utilized - these include a dose of 250 mg monthly ('approved dose'), an initial 500 mg followed by 250 mg on days 14 and 28, and thereafter 250 mg every 28 days ('loading dose'), or 500 mg on days 0, 14 and 28, and thereafter every 28 days ('high dose'). This article will review its unique mode of action and preclinical data, as well as clinical data for different dosing regimens and data for its combination with aromatase inhibitors. Fulvestrant is a well-tolerated drug and its toxicities will also be reviewed. The optimal position of fulvestrant in sequential endocrine therapy has yet to be defined. PMID- 22050014 TI - Chimeric antigen receptors: a costimulatory boost promotes immunological memory to B-cell malignancies. AB - Cellular immunotherapies offer perhaps the best proof of concept of the ability of immune cells to eradicate malignancy. However, the majority of these data derive from either the use of expanded tumor-infiltrating lymphocytes to treat metastatic melanoma or the use of donor lymphocytes in relapsed hematological malignancies following allogeneic hematopoietic stem cell transplantation. Genetic engineering of T cells to redirect specificity against tumor-associated antigens potentially overcomes one of the major hurdles to more widespread application. Despite early evidence of possible activity, limited in vivo expansion and persistence of adoptively transferred cells has been associated with disappointing clinical efficacy. A report from Porter and colleagues now demonstrates more fully the potential of such genetic modification in a patient with chronic lymphocytic leukemia, illustrating that when delivered in the right setting with appropriate costimulatory signaling, these cells can expand and persist, and in doing so effect quite remarkable anti-tumor activity. PMID- 22050015 TI - Role of bacillus Calmette-Guerin in the treatment of advanced melanoma. AB - Early trials of Bacillus Calmette-Guerin (BCG)-based immunotherapy for melanoma consistently show a trend toward improved clinical outcomes in patients treated with BCG compared with observation alone. As an extension of these findings, investigators have initiated the Malignant Melanoma Active Immunotherapy (MMAIT) trials in patients with stage III (MMAIT-III) and stage IV (MMAIT-IV) disease. The overall survival of the patients receiving BCG plus placebo was much better than expected in both studies, thus suggesting a potential for BCG as an adjuvant after the resection of advanced disease. The work contained herein will explore the clinical rationale for adjuvant BCG in future trials focused on the treatment of patients with advanced malignant melanoma. PMID- 22050016 TI - Anaplastic lymphoma kinase as a new target for the treatment of non-small-cell lung cancer. AB - The anaplastic lymphoma kinase (ALK) gene rearrangement identifies a distinct molecular subset in non-small-cell lung cancer (NSCLC) populations susceptible to targeted inhibition. It consists of a small inversion in the short arm of chromosome 2 between exon 20 of the ALK gene and different exons of the echinoderm microtubule-associated protein-like (EML4) gene. This translocation leads to a chimeric protein with constitutive activation of ALK that possesses an oncogenic activity demonstrated both in vitro and in vivo. Other rare translocation partners for ALK other than EML4 may be found in lung cancers, including TRK-fused gene (TFG) and kinesin family member 5B (KIF5B). ALK-positive patients represent 5-6% of all NSCLCs and they seem to have particular clinicopathological and molecular features. Recently, Phase I-II trial results of crizotinib, a potent dual c-MET and ALK inhibitor, demonstrated its dramatic efficacy in ALK-positive patients with advanced NSCLC. This article will present knowledge on the characteristics of ALK-positive patients, discuss the different methods of ALK rearrangement detection and focus on clinical results of crizotinib. PMID- 22050017 TI - Role of sorafenib in renal cell carcinoma: focus on elderly patients. AB - Mounting evidence suggests that, in order to optimize therapeutic benefits, it is important to consider the range of parameters and characteristics relevant to each individual patient. Of note, the six targeted therapies currently approved for the treatment of advanced/metastatic renal cell carcinoma have not been evaluated in all relevant settings and in all prognostic groups. Among different agents currently licensed for the treatment of renal cell carcinoma, sorafenib was the first therapy to show improvements in progression-free survival and overal survival in Phase III trials. This article will discuss the current role of sorafenib in the treatment of elderly patients with renal cell carcinoma. PMID- 22050018 TI - New developments in melanoma: utility of ultrasound imaging (initial staging, follow-up and pre-SLNB). AB - Melanoma incidence is still increasing, but the mortality rate has remained unchanged. Lymph node metastases are the single most important prognostic factor for stage I/II melanoma patients. Currently, the standard of care with regard to the staging of these patients is the surgical sentinel node procedure. Ultrasound is not routine for the diagnostic work-up of primary melanomas. Some may use ultrasound for the preoperative assessment of the tumor thickness and lymphatic drainage, but this has not found wide application. For the follow-up of melanoma patients, ultrasound has been proven to be superior to physical examination for the detection of lymph node metastases. A meta-analysis has shown that ultrasound is superior to computed tomography (CT) and/or positron emission tomography (PET) CT for the detection of lymph node metastases, whereas PET-CT was superior for the detection of distant visceral metastases. Ultrasound of regional lymph nodes has been incorporated into many national guidelines across Europe and in Australia for the follow-up of melanoma patients. A new avenue for ultrasound (US)-guided fine-needle aspiration cytology (FNAC) is the pre-sentinel node modality. Like the situation in breast and thyroid cancer, US-FNAC, a minimally invasive procedure, may decrease the need for surgical sentinel node staging. New ultrasound morphology criteria have significantly increased the sensitivity of this technique. Peripheral perfusion is an early sign of metastases (77% sensitivity, 52% positive-predictive value), whereas balloon-shaped lymph node was a late sign of metastases (30% sensitivity, 96% positive-predictive value). Together, these new ultrasound morphology criteria were able to accurately demonstrate metastases in 65% of sentinel node-positive patients. Future perspectives of ultrasound in melanoma include the start of a large multicenter, multicountry validation study - USE-FNAC - by the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group. In light of new and promising adjuvant therapies, the need for ultrasound staging might increase rapidly. PMID- 22050019 TI - Debulking surgery in advanced melanoma. AB - In general, patients with stage IV melanoma have poor survival. However, there are subsets of stage IV melanoma patients who are candidates for surgical debulking. There is a growing body of retrospective evidence about clinicians being able to better select patients who may benefit from surgical resection in isolated stage IV disease. In addition, palliative-type resections may improve quality of life in selected cases. In this article, we discuss how recent advances in effective systemic therapies for melanoma may impact the clinical use of debulking surgery in melanoma patients. We also review the available literature about the rationale, risks, benefits and selection of patients for these procedures. PMID- 22050020 TI - End points for Phase II trials in recurrent glioblastoma: the cornerstone for a new era. AB - In recent years, novel approaches have been developed in medical oncology, and antiangiogenic treatments have had a role in the treatment of colorectal, renal and breast cancers. The role of these agents in brain tumors is, however, controversial, since these drugs may induce modifications in neuroradiological patterns without even affecting the real tumor burden. Moreover, despite the intriguing results in terms of progression-free survival and response rate obtained with these agents, data about survival are superimposable with historical controls. Thus, there is a need for solid end points to evaluate the role of these agents in Phase II trials in the field of neuro-oncology. PMID- 22050021 TI - Evolution of care for patients with relapsed glioblastoma. AB - Glioblastoma is the most common and aggressive form of brain tumor in adults and has a poor prognosis and a high recurrence rate despite optimal care. The management of patients with relapsed glioblastoma is challenging, with no widely agreed standard of care. Different chemotherapy and radiotherapy combination treatment strategies provide only modest benefits. Recently, several novel agents, including bevacizumab and XL-184, have demonstrated promising results in Phase II trials with their further evaluation ongoing in Phase III randomized trials. Interpreting the data from such trials is a key challenge in glioblastoma, highlighting the need for relevant and standardized patient assessment techniques. Data from ongoing and planned trials should help to define optimal treatment strategies for this disease. PMID- 22050022 TI - Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases: an update. AB - Brain metastases are unfortunately a common occurrence in patients with cancer. Whole-brain radiation therapy (WBRT) is still considered the standard of care in the treatment of brain metastases. Stereotactic radiosurgery (SRS) offers the additional ability to treat tumors with relative sparing of normal brain tissue in a single fraction. While the addition of SRS to WBRT has been shown to improve survival and local tumor control in selected patients, the idea of deferring WBRT in order to avoid its effects on normal tissues and using SRS alone continues to generate significant discussion and interest. Three recent randomized trials from Japan, Europe and the MD Anderson Cancer Center (TX, USA) have attempted to address this issue. In this article, we update a previous review by discussing these trials to compare the outcomes for SRS alone versus SRS plus WBRT for limited metastases. We also discuss recent nonrandomized evidence for the use of SRS alone for oligometastatic disease. PMID- 22050023 TI - Role of tyrosine kinase inhibitors in the management of high-grade gliomas. AB - Recent years have witnessed an explosion of promising therapies for cancer patients. New insights into the biology of malignancies have led to the development of targeted agents with the potential to improve survival and quality of life. One of the most important classes of these compounds are tyrosine kinase inhibitors. These agents are beginning to offer a clinically relevant benefit to patients with tumors that until recently have been refractory to medical therapies. High-grade gliomas represent one class of medically refractory solid tumors. This article summarizes the state of the art of tyrosine kinase inhibitors in the management of patients with high-grade gliomas. PMID- 22050024 TI - Meningioma: review of the literature with emphasis on the approach to radiotherapy. AB - Meningiomas are tumors that arise from arachnoid cap cells, which surround and adhere to the dura mater. Currently, meningiomas comprise 13-30% of primary intracranial tumors and are only less frequent than gliomas. In this article an overview of meningiomas is presented, with brief mention to their epidemiology, clinical presentation, histopathological and imaging features. The main therapies for meningiomas are also presented, focusing on radiation. In this article the authors conclude that the epidemiological, imaging and histopathological features and the clinical presentation of meningiomas are well-defined. Despite the need for randomized trials and larger studies with long median follow-up, radiotherapy can be used as an alternative treatment to surgery either as a first-line treatment or at its recurrence. Various conventional radiotherapy techniques can be employed for residual tumor or at recurrence. PMID- 22050027 TI - Retraction. PMID- 22050025 TI - Brain cancer immunoediting: novel examples provided by immunotherapy of malignant gliomas. AB - A number of studies in murine models have suggested that the immune system may edit different tumors by forcing their expression profiles so that they escape immune reactions and proliferate. Glioblastoma (GB), the most frequent and aggressive primary brain tumor, provides a good example of this, thanks to the production of numerous immunosuppressive molecules (with TGF-beta being of paramount importance), downregulation of the MHC complex and deregulation of the potential for antigen presentation by the surrounding microglia. Given that surgery, radiotherapy and chemotherapy with available protocols have limited effects on the survival of GB patients, different immunotherapy strategies have been developed, based on the use of dendritic cells, antibodies and peptide vaccination. Presently, bevacizumab, a humanized anti-VEGF antibody, provides the most successful example for immune-based treatment of GB, however, its action is limited in time, as the often tumor relapses due to still undefined immunoediting mechanisms. Altered function of EGF receptor-driven pathways is common in GB and is most frequently due to the presence of a deleted form named EGFRvIII, providing a unique cancer epitope that has been targeted by immunotherapy. A recent trial of GB immunotherapy based on vaccination with the EGFRvIII peptide has shown clinical benefit: interestingly most GBs at relapse were negative for EGFRvIII expression, a relevant, direct example of cancer immunoediting. Investigations on the mechanisms of GB immunoediting will lead to an increased understanding of the biology of this malignancy and hopefully provide novel therapeutic targets. PMID- 22050028 TI - Anatomic assessment of variations in myocardial approaches to the atrioventricular node. AB - INTRODUCTION: The tissues in the posteroinferior atrioventricular (AV) junction around the AV node are important in procedures for ablating and manipulation of catheters in and around the coronary sinus (CS). However, information with regard to the histological arrangement of perinodal myocardium relative to the CS is lacking. METHODS AND RESULTS: We examined 21 postmortem human hearts without any abnormalities (9 women; mean age 68.8 +/- 14.3 years). After making measurements, the posteroinferior AV junction was removed and processed for histology. Sections were cut parallel to the septum. We assessed the myocardial arrangements from the atrial septum and the CS toward the AV nodal tissue, including the transitional cell zone, and measured the dimensions between the compact AV node and the CS, and the circumference of the CS. We observed 3 patterns of myocardial approaches to the AV node: extension of myocardium from the atrial septum (Group A; n = 6); extension of CS musculature (Group B; n = 6); and both septal and CS musculature (Group C; n = 9). The distance between the AV node and the CS in Group A was significantly longer than in the other groups (mean 11.5 +/- 3.1 mm, 1.7 +/- 0.6 mm, 3.8 +/- 1.5 mm, respectively; P < 0.0001), and the circumference of the CS in Group B was longer than in Group A (mean 31.1 +/- 7.9 mm*, 44.4 +/- 8.4 mm*, 33.7 +/- 6.9 mm, respectively; P < 0.05). CONCLUSION: The myocardial approaches including the transitional cell zone toward the AV node are variable in normal hearts. The location and size of the CS can affect the myocardial arrangements and the area of transitional cells around the AV node. PMID- 22050029 TI - Impact of electrocardiographic interpretability on outcome in patients referred for stress testing. AB - BACKGROUND: There is limited insight into the association of electrocardiographic interpretability with outcome in patients referred for stress testing. METHODS: Exercise echocardiography was performed in 8226 patients with known or suspected coronary artery disease. Electrocardiograms were considered uninterpretable in the presence of left bundle-branch block (LBBB), left ventricular hypertrophy (LVH) with strain, repolarization abnormalities because of digitalis therapy, ventricular paced rhythm, preexcitation or ST depression >= 0.1 mV because of other causes. End points were all-cause mortality, cardiac death and hard cardiac events (i.e. cardiac death or nonfatal myocardial infarction). RESULTS: A total of 2450 patients had uninterpretable electrocardiograms. During a follow-up period of 4.1 +/- 3.5 years, there were 1011 deaths (of which 478 were cardiac deaths) and 1069 patients experienced a hard cardiac event. The 5-year rates of death, cardiac death and hard cardiac events were, respectively, 18.7%, 10.9% and 18.8% in patients with uninterpretable ECGs, compared with 9.5%, 4.1% and 10.9% in those with interpretable ECGs (P < 0.001). After covariate adjustment, lack of ECG interpretability remained an independent predictor of all-cause mortality (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.08-1.44, P = 0.002), cardiac death (HR 1.63, 95% CI 1.32-2.01, P < 0.001) and hard cardiac events (HR 1.28, 95% CI 1.11-1.47, P < 0.001). When the specific ECG abnormalities were included as covariates, LBBB, LVH and digitalis therapy remained predictors of cardiac death; LBBB and LVH were predictors of hard cardiac events, and LVH remained predictive of all-cause mortality. CONCLUSION: Uninterpretable ECGs portend a worse prognosis in patients referred for stress testing. PMID- 22050031 TI - Temporal dynamics of periphyton exposed to tetracycline in stream mesocosms. AB - Significant amounts of antibiotics enter the environment via point and nonpoint sources. We examined the temporal dynamics of tetracycline exposure to stream periphyton and associated organisms across a logarithmically dosed-series of experimental mesocosms, designed to mimic natural conditions. Target in-stream tetracycline exposures were based on environmentally relevant concentrations in aquatic ecosystems throughout the United States (<1-100 MUg L(-1)). Significant changes in the stream biotic community were observed within 7 days with in-stream tetracycline concentrations as low as 0.5 MUg L(-1), including significant changes in antibiotic resistance, bacteria abundance and productivity, algae biomass, cyanobacteria, organic biomass, and nematodes. These effects were magnified with increased exposure time and dosing concentration. Recovery of the periphyton community after 28 days of exposure was dependent upon the tetracycline dose. At the highest doses, 10 and 100 MUg L(-1), bacteria productivity recovered; however, bacteria, algae, and nematode abundance did not recover at the same rate and remained low even after a 28-day recovery period (of nondosing). This study demonstrates that tetracycline exposure under near-natural conditions and at concentrations currently observed in aquatic environments may have important consequences for the structure and function of stream periphyton and, potentially, public health via increasing resistance of naturally occurring bacteria. PMID- 22050030 TI - Comparison of intranasal methamphetamine and d-amphetamine self-administration by humans. AB - AIMS: There are no studies directly comparing self-administration of methamphetamine and d-amphetamine by humans. This study compared intranasal methamphetamine- and d-amphetamine self-administration and characterized the mood, performance and physiological effects produced by the drugs. DESIGN: A randomized, double-blind, placebo-controlled, cross-over study. SETTING: An out patient research unit at the New York State Psychiatric Institute. PARTICIPANTS: Male recreational methamphetamine users (n = 13). MEASUREMENTS: Five 2-day blocks of sessions were conducted. On the first day of each block, participants 'sampled' a single methamphetamine or d-amphetamine dose (0, 12, 50 mg/70 kg) and a monetary reinforcer ($5 or $20). Amphetamine plasma levels, cardiovascular, mood, and psychomotor performance effects were assessed before drug administration and repeatedly thereafter. On the second day of each block, participants chose between the sampled reinforcers (drug or money). FINDINGS: There were no significant differences between the drugs on the majority of measures. Under the $5 condition, both amphetamines increased self-administration dose-dependently, with 41% drug choices overall. Under the $20 condition, only 17% drug options were selected. Both drugs increased cardiovascular activity and 'positive' mood, although methamphetamine produced more prominent effects on some measures (e.g. heart rate and ratings of 'high'). CONCLUSIONS: Methamphetamine and d-amphetamines appear to produce a similar dose-related profile of effects in humans, which supports their equivalence for abuse potential. PMID- 22050032 TI - Correlated electron dynamics: how aromaticity can be controlled. AB - In this Article, we show that the aromaticity of a molecule can be turned off by controlling the electron dynamics. We present a controlled switching from the aromatic ground state of benzene to two different nonaromatic states, using a laser pulse. The propagation of the molecular wave function is carried out with the time-dependent configuration interaction method. The laser pulse for switching between the ground and excited states is optimized using optimal control theory. Bond orders and Mulliken charges serve as an aromaticity criterion. The nonaromatic target states exhibit localized bonds and partial charges on the carbon atoms; these localized electrons circulate on an attosecond time scale in the ring system. PMID- 22050033 TI - Hydroxyl radical (OH*) reaction with guanine in an aqueous environment: a DFT study. AB - The reaction of hydroxyl radical (OH(*)) with DNA accounts for about half of radiation-induced DNA damage in living systems. Previous literature reports point out that the reaction of OH(*) with DNA proceeds mainly through the addition of OH(*) to the C?C bonds of the DNA bases. However, recently it has been reported that the principal reaction of OH(*) with dGuo (deoxyguanosine) is the direct hydrogen atom abstraction from its exocyclic amine group rather than addition of OH(*) to the C?C bonds. In the present work, these two reaction pathways of OH(*) attack on guanine (G) in the presence of water molecules (aqueous environment) are investigated using the density functional theory (DFT) B3LYP method with 6 31G* and 6-31++G** basis sets. The calculations show that the initial addition of the OH(*) at C(4)?C(5) double bond of guanine is barrier free and the adduct radical (G-OH(*)) has only a small activation barrier of ca. 1-6 kcal/mol leading to the formation of a metastable ion-pair intermediate (G(*+)---OH(-)). The formation of ion-pair is a result of the highly oxidizing nature of the OH(*) in aqueous media. The resulting ion-pair (G(*+)---OH(-)) deprotonates to form H(2)O and neutral G radicals favoring G(N(1)-H)(*) with an activation barrier of ca. 5 kcal/mol. The overall process from the G(C(4))-OH(*) (adduct) to G(N(1)-H)(*) and water is found to be exothermic in nature by more than 13 kcal/mol. (G-OH(*)), (G(*+)---OH(-)), and G(N(1)-H)(*) were further characterized by the CAM-B3LYP calculations of their UV-vis spectra and good agreement between theory and experiment is achieved. Our calculations for the direct hydrogen abstraction pathway from N(1) and N(2) sites of guanine by the OH(*) show that this is also a competitive route to produce G(N(2)-H)(*), G(N(1)-H)(*) and H(2)O. PMID- 22050034 TI - Does the epidermal growth factor receptor play a role in the progression of thyroid cancer? PMID- 22050035 TI - Historical note: TSH suppression for thyroid cancer. PMID- 22050039 TI - Combining multiple imputation and inverse-probability weighting. AB - Two approaches commonly used to deal with missing data are multiple imputation (MI) and inverse-probability weighting (IPW). IPW is also used to adjust for unequal sampling fractions. MI is generally more efficient than IPW but more complex. Whereas IPW requires only a model for the probability that an individual has complete data (a univariate outcome), MI needs a model for the joint distribution of the missing data (a multivariate outcome) given the observed data. Inadequacies in either model may lead to important bias if large amounts of data are missing. A third approach combines MI and IPW to give a doubly robust estimator. A fourth approach (IPW/MI) combines MI and IPW but, unlike doubly robust methods, imputes only isolated missing values and uses weights to account for remaining larger blocks of unimputed missing data, such as would arise, e.g., in a cohort study subject to sample attrition, and/or unequal sampling fractions. In this article, we examine the performance, in terms of bias and efficiency, of IPW/MI relative to MI and IPW alone and investigate whether the Rubin's rules variance estimator is valid for IPW/MI. We prove that the Rubin's rules variance estimator is valid for IPW/MI for linear regression with an imputed outcome, we present simulations supporting the use of this variance estimator in more general settings, and we demonstrate that IPW/MI can have advantages over alternatives. IPW/MI is applied to data from the National Child Development Study. PMID- 22050040 TI - Once-daily topical brimonidine tartrate gel 0.5% is a novel treatment for moderate to severe facial erythema of rosacea: results of two multicentre, randomized and vehicle-controlled studies. AB - BACKGROUND: Erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity. Brimonidine tartrate (BT) is a highly selective alpha(2) adrenergic receptor agonist with vasoconstrictive activity. OBJECTIVE: To determine the optimal concentration and dose regimen of topical BT gel for the treatment of erythema of rosacea and to evaluate its efficacy and safety. METHODS: In study A, 122 subjects were randomized to receive a single application of BT 0.07%, 0.18%, 0.5% or vehicle. In study B (4-week treatment and 4-week follow-up), 269 subjects were randomized to receive BT 0.5% once daily, BT 0.18% once daily, vehicle once daily, BT 0.18% twice daily or vehicle twice daily. Evaluations included Clinician's Erythema Assessment (CEA), Patient's Self Assessment (PSA), Chroma Meter measurements and adverse events. RESULTS: In study A, a single application of topical BT gel reduced facial erythema in a dose dependent fashion. A significant difference between BT 0.5% and vehicle in Chroma Meter redness value was observed from 30min to 12h after application. In study B, BT 0.5% once daily had a statistically superior success profile (defined as a two grade improvement on both CEA and PSA over 12h) compared with vehicle once daily on days 1, 15 and 29 (all P<0.001). No tachyphylaxis, rebound of erythema or aggravation of other disease signs (telangiectasia, inflammatory lesions) was observed. All regimens were safe and well tolerated with similarly low incidence of adverse events. CONCLUSIONS: Once-daily BT gel 0.5% is well tolerated and provides significantly greater efficacy than vehicle gel for the treatment of moderate to severe erythema of rosacea. PMID- 22050041 TI - Ketjenblack carbon supported amorphous manganese oxides nanowires as highly efficient electrocatalyst for oxygen reduction reaction in alkaline solutions. AB - A composite air electrode consisting of Ketjenblack carbon (KB) supported amorphous manganese oxide (MnOx) nanowires, synthesized via a polyol method, is highly efficient for the oxygen reduction reaction (ORR) in a Zn-air battery. The low-cost and highly conductive KB in this composite electrode overcomes the limitations due to low electrical conductivity of MnOx while acting as a supporting matrix for the catalyst. The large surface area of the amorphous MnOx nanowires, together with other microscopic features (e.g., high density of surface defects), potentially offers more active sites for oxygen adsorption, thus significantly enhancing ORR activity. In particular, a Zn-air battery based on this composite air electrode exhibits a peak power density of ~190 mW/cm2, which is far superior to those based on a commercial air cathode with Mn3O4 catalysts. PMID- 22050042 TI - Molecular fluorescence, phosphorescence, and chemiluminescence spectrometry. PMID- 22050043 TI - Expression of inducible nitric oxide synthase (iNOS) in the azoospermic human testis. AB - Azoospermia, which is the absence of spermatozoa in the ejaculate, is not a rare cause of male infertility. Inducible nitric oxide synthase (iNOS) is a calcium independent NOS, which is present in the testis and involved in spermatogenesis, and apoptosis of Sertoli and germ cells. Twenty idiopathic infertile men presenting nonobstructive azoospermia were enrolled in this study, and testicular sperm extraction procedures were performed. Tissue extracts were dissected, and the fluid samples were investigated to determine the presence of spermatozoa. Histologic evaluation of the spermatozoa-present samples revealed that seminiferous tubules were normal and were lined by Sertoli cells and spermatogenic cells. However, in the spermatozoa-absent samples, the diameter of the seminiferous tubules was small, and Sertoli-cell-only syndrome was determined in most of the tubules. iNOS expression was very weak in Sertoli cells, germ cells, and in Leydig cells in the spermatozoa-present group. In the spermatozoa absent group, the immunostaining was very intense in Sertoli and Leydig cells. Electron microscopy findings were supported the histologic results. In conclusion, complete germ cell loss and intense expression of iNOS in the Sertoli and Leydig cells in the spermatozoa-absent groups of azoospermic human testis suggest an essential role of iNOS in spermatogenesis. PMID- 22050044 TI - Combined therapy with low-dose omalizumab and intravenous immunoglobulin for severe atopic dermatitis. Report of four cases. PMID- 22050046 TI - Colic in competing endurance horses presenting to referral centres: 36 cases. AB - REASONS FOR PERFORMING STUDY: Colic is a common reason for elimination from equine endurance competitions and has recently been identified as the leading cause of mortality in this group of horses. Hydration and electrolyte derangements are often severe, but are probably related to endurance exercise and not necessarily the episode of colic. Better understanding of the causes of colic and the expected outcome is needed to guide treatment decisions in endurance horses. OBJECTIVES: To describe the history, case details, clinical examination, laboratory, treatment and outcomes for horses presenting to equine referral centres for treatment of colic associated with endurance competition and to identify variables associated with prolonged hospitalisation. METHODS: Thirty-six horses from 2 equine referral centres were included in the analysis. In addition to descriptive statistics, Cox proportional hazards models were used to evaluate factors associated with length of hospitalisation. RESULTS: A diagnosis of open or ileus was made in the majority of horses (56%). Salmonellosis and enteritis (Salmonella negative) were also recognised (16%). Exploratory abdominal surgery was performed in 5 of the horses. Only one of 36 horses did not survive to discharge. Previous eliminations from competition (negative association) and total i.v. fluids within the first 24 h (positive association) of admission were both associated with length of hospitalisation. CONCLUSIONS: Endurance horses with colic typically respond to medical treatment but in some cases hospitalisation may be prolonged. The role of Salmonella infections in endurance horses with colic requires further research. POTENTIAL RELEVANCE: Despite potentially severe clinical and laboratory derangements, equine practitioners should make owners aware that the prognosis for competing endurance horses with colic is good when treated appropriately. PMID- 22050045 TI - Nucleostemin and TWIST as predictive markers for recurrence after neoadjuvant chemotherapy for esophageal carcinoma. AB - We recently demonstrated that overexpression of the nucleolar GTP-binding protein nucleostemin drives the fraction of genetically-defined tumor cells that exhibit markers and tumorigenic properties of tumor initiating cells. More specifically, cells that constitutively express elevated levels of nucleostemin exhibit increased TWIST expression; expression of genes that induced pluripotent stem cells; enhanced radioresistance; tumor formation, even when small numbers of cells are implanted; and an increased propensity to metastasize. An immunohistochemical analysis of cancer stem cell markers, such as nucleostemin and TWIST has not been conducted in surgically-resected esophageal squamous cell carcinomas after neoadjuvant chemotherapy. In the present study, we examined the expression of CD133, CD44, nucleostemin, guanine nucleotide-binding protein-like 3-like, and TWIST by immunohistochemistry in a series of 54 surgically-resected specimens of esophageal squamous cell carcinomas after neoadjuvant chemotherapy. We identified that high nucleostemin proportion, TWIST intensity, and advanced pathological N stage were significantly correlated with poor relapse-free survival. Together, these observations imply nucleostemin and TWIST as the predictive markers for postoperative recurrence. PMID- 22050047 TI - Reduction of latent infection and enhancement of disease resistance in muskmelon by preharvest application of harpin. AB - Latent infection was analyzed when harpin at 50 mg/L was sprayed on muskmelon 4 times at four different stages: florescence, young fruit, fruit enlarging, and netting periods. Results showed that the latent infection was significantly lower in sprayed muskmelons than in the control fruit. Meanwhile, the activities of peroxidase, phenylalanine ammonia-lyase, beta-1,3-glucanase, and chitinase increased significantly in the fruit treated with harpin. It also resulted in an increase of contents of total phenolic compounds, flavanoids, and lignin. In addition, the treatment of harpin increased the activity of superoxide dismutase, enhanced the content of hydrogen peroxide, and reduced catalase activity. Furthermore, harpin treatments contributed to the reinforcement of cell walls of pericarp in fruit, the reduction of postharvest decay, and the improvement of postharvest qualities. These results suggested that harpin effectively participated in inducing resistance and could be a new strategy for preventing latent infection in muskmelon. PMID- 22050048 TI - Fifty years of brief intervention effectiveness trials for heavy drinkers. PMID- 22050049 TI - Erratum. PMID- 22050051 TI - Preclinical and clinical characterization of the selective 5-HT(1A) receptor antagonist DU-125530 for antidepressant treatment. AB - BACKGROUND AND PURPOSE: The antidepressant efficacy of selective 5-HT reuptake inhibitors (SSRI) and other 5-HT-enhancing drugs is compromised by a negative feedback mechanism involving 5-HT(1A) autoreceptor activation by the excess 5-HT produced by these drugs in the somatodendritic region of 5-HT neurones. 5-HT(1A) receptor antagonists augment antidepressant-like effects in rodents by preventing this negative feedback, and the mixed beta-adrenoceptor/5-HT(1A) receptor antagonist pindolol improves clinical antidepressant effects by preferentially interacting with 5-HT(1A) autoreceptors. However, it is unclear whether 5-HT(1A) receptor antagonists not discriminating between pre- and post-synaptic 5-HT(1A) receptors would be clinically effective. EXPERIMENTAL APPROACH: We characterized the pharmacological properties of the 5-HT(1A) receptor antagonist DU-125530 using receptor autoradiography, intracerebral microdialysis and electrophysiological recordings. Its capacity to accelerate/enhance the clinical effects of fluoxetine was assessed in a double-blind, randomized, 6 week placebo controlled trial in 50 patients with major depression (clinicaltrials.gov identifier NCT01119430). KEY RESULTS: DU-125530 showed equal (low nM) potency to displace agonist and antagonist binding to pre- and post-synaptic 5-HT(1A) receptors in rat and human brain. It antagonized suppression of 5 hydroxytryptaminergic activity evoked by 8-OH-DPAT and SSRIs in vivo. DU-125530 augmented SSRI-induced increases in extracellular 5-HT as effectively as in mice lacking 5-HT(1A) receptors, indicating a silent, maximal occupancy of pre synaptic 5-HT(1A) receptors at the dose used. However, DU-125530 addition to fluoxetine did not accelerate nor augment its antidepressant effects. CONCLUSIONS AND IMPLICATIONS: DU-125530 is an excellent pre- and post-synaptic 5-HT(1A) receptor antagonist. However, blockade of post-synaptic 5- HT(1A) receptors by DU 125530 cancels benefits obtained by enhancing pre-synaptic 5 hydroxytryptaminergic function. PMID- 22050052 TI - Review article: the benefits of pharmacogenetics for improving thiopurine therapy in inflammatory bowel disease. AB - BACKGROUND: Thiopurines represent an effective and widely prescribed therapy in inflammatory bowel disease (IBD). Concerns about toxicity, mainly resulting from a wide inter-individual variability in thiopurine metabolism, restrict their use. Optimal thiopurine dosing is challenging for preventing adverse drug reactions and improving clinical response. AIM: To review efficacy and toxicity of thiopurines in IBD. To provide pharmacogenetic-based therapeutic recommendations. METHODS: We conducted a query on PubMed database using 'inflammatory bowel disease', 'thiopurine', 'azathioprine', '6-mercaptopurine', 'TPMT', 'pharmacogenetics', 'TDM', and selected relevant articles, especially clinical studies. RESULTS: Thiopurine metabolism - key enzyme: thiopurine S methyltransferase (TPMT) - modulates clinical response, as it results in production of the pharmacologically active and toxic metabolites, the thioguanine nucleotides (6-TGN). Adjusting dosage according to TPMT status and/or metabolite blood levels is recommended for optimising thiopurine therapy (e.g. improving response rate up to 30% or decreasing haematological adverse events of 25%). Other enzymes or transporters of interest, as inosine triphosphatase (ITPase), glutathione S-transferase (GST), xanthine oxidase (XO), aldehyde oxidase (AOX), methylene tetrahydrofolate reductase (MTHFR) and ATP-binding cassette sub-family C member 4 (ABCC4) are reviewed and discussed for clinical relevance. CONCLUSIONS: Based on the literature data, we provide a therapeutic algorithm for thiopurines therapy with starting dose recommendations depending on TPMT status and thereafter dose adjustments according to five metabolite profiles identified with therapeutic drug monitoring (TDM). This algorithm allows a dosage individualisation to optimise the management of patients under thiopurine. Furthermore, identification of new pharmacogenetic biomarkers is promising for ensuring maximal therapeutic response to thiopurines with a minimisation of the risk for adverse events. PMID- 22050054 TI - Winter and venous thromboembolism: a dangerous liaison? PMID- 22050053 TI - Covalent layer-by-layer assembly of hyperbranched polyether and polyethyleneimine: multilayer films providing possibilities for surface functionalization and local drug delivery. AB - A convenient and simple route to multifunctional surface coatings via the alternating covalent layer-by-layer (LBL) assembly of p-nitrophenyloxycarbonyl group-terminated hyperbranched polyether (HBPO-NO(2)) and polyethylenimine (PEI) is described. The in situ chemical reaction between HBPO-NO(2) and PEI onto aminolyzed substrates was rapid and mild. Results from ellipsometry measurements, contact angle measurements, and ATR-FTIR spectra confirmed the successful LBL assembly of the building blocks, and the surface reactivity of the multilayer films with HBPO-NO(2) as the outmost layer was demonstrated by the immobilization of an amine-functionalized fluorophore. Furthermore, a biomimetic surface was achieved by surface functionalization of the multilayer films with extracellular matrix protein collagen to promote the adhesion and growth of cells. The studies on the drug loading and in vitro release behaviors of the multilayer films demonstrated their application potentials in local delivery of hydrophilic and hydrophobic therapeutic agents. PMID- 22050055 TI - Is periodic fasting really good for reducing cardiovascular risk and improving heart health? PMID- 22050056 TI - Calcium supplementation and vitamin D: a trigger for adverse cardiovascular events? PMID- 22050059 TI - Highlights of the 2011 scientific sessions of the Congress of the Heart Failure Association of the European Society of Cardiology. AB - The Annual Scientific Sessions of the Heart Failure Association of the European Society of Cardiology was held in Gothenburg, Sweden, 21-24 May 2011. Over 700 abstracts, along with many invited programs and several satellite programs were presented. Some of the late-breaking clinical trials are summarized here. PMID- 22050058 TI - Ranolazine versus amiodarone for prevention of postoperative atrial fibrillation. AB - Postoperative atrial fibrillation (AF) is a major complication of cardiothoracic surgery, leading to significant consequences, including a higher rate of stroke, longer hospital stays and increased costs. Amiodarone is among the most widely used agents for prevention of postoperative AF. Ranolazine, a US FDA-approved antianginal agent, has been shown to effectively, safely prevent and terminate nonpostoperative AF in both experimental and clinical studies. In a recent publication, Miles and colleagues directly compared the efficacy and safety of amiodarone and ranolazine for prevention of postoperative AF in 393 patients. The patients were pretreated with amiodarone and ranolaizne for >1 week and 1 day, respectively, and the treatment continued for 10-14 days after surgery. Following coronary artery bypass grafting (CABG), AF occurred in 26.5% of patients taking amiodarone and in 17.5% of patients taking ranolazine (34% reduction; p < 0.035). No differences in adverse events between the two groups of patients were recorded. The results of this retrospective nonrandomized single-center study indicate that ranolazine may be used to effectively and safely prevent postoperative AF. These results need to be confirmed in a larger randomized study. If confirmed, ranolazine may be a good choice for preventing AF in patients undergoing CABG. PMID- 22050060 TI - Drug-eluting stent thrombosis after 2029 days of placement: longest ever reported interval between drug-eluting stent placement and very late thrombosis. AB - In this era of very wide-spread use of percutaneous coronary intervention for the management of coronary artery disease, the appropriate duration of antiplatelet therapy after drug-eluting stent implantation still remains a subject of debate. Current recommendations from the American College of Cardiology/American Heart Association (2007) is to continue treatment with aspirin and clopidogrel for 1 year and then continue with aspirin only. However, cases of very late stent thrombosis (more than 12 months postimplantation) are being increasingly reported in literature. In this article we report a case of thrombosis as a result of drug eluting stent placement after almost 67 months (2029 days), which to our knowledge, is the longest reported duration between the implantation of drug eluting stent and occurrence of vascular event associated with very late stent thrombosis. PMID- 22050061 TI - Primary percutaneous coronary intervention for the treatment of a patient with cardiogenic shock due to acute total occlusion of unprotected left main coronary artery without supportive collateral flow. AB - Total occlusion of unprotected left main coronary artery (LMCA) is rarely encountered in clinical practice and the incidence cannot be determined precisely, since most of the patients die before hospital admission. Malignant arrhythmia, cardiogenic shock or sudden death due to pump failure develops in most of these patients. The cases complicated by cardiogenic shock have bad prognosis in both the short and long term, despite the advancements in reperfusion treatments. Successful treatment of sudden total occlusion of unprotected LMCA has been rarely reported. Over the last decade, many cases and comparisons in patients with LMCA lesions were reported on percutaneous interventions for unprotected LMCA using different stent and stenting procedures or in comparison to coronary bypass surgery. On the other hand, these patients either had stable coronary artery disease or a partially occluded LMCA in the setting of acute coronary syndromes with well supporting collateral flow. In our case, a 50 year-old male patient with cardiogenic shock and extensive anterior ST elevation myocardial infarction due to acute total occlusion of unprotected LMCA, who was not receiving collateral flow from the right coronary system, was treated successfully through primary percutaneous coronary angioplasty, was presented. In our case, there was an totally occluded unprotected LMCA without any supportive coronary flow to left system. In this regard, our case is unique in literature. PMID- 22050063 TI - Current status, challenges and future directions of drug-eluting balloons. AB - For the past 30 years, contemporary coronary and endovascular interventions utilized balloon catheters, bare metal- and drug-eluting stents (DES) to recanalize narrowed vessels. Despite this, the quest for outcome optimization is ongoing for specific lesions and patients. Drug-eluting balloons (DEBs) are among the latest technologies proposed to overcome the limitations of DES, such as stent thrombosis and the dependency on long-term dual antiplatelet therapy. In the large part, DEBs were introduced as a substitute for DES in the treatment of in-stent restenosis and perhaps in certain de novo lesion subsets. DEBs have been tested in several clinical scenarios with encouraging preliminary results. This article will discuss the rationale for developing DEBs, basic concepts and available DEB platforms, along with preclinical studies and clinical experience to support the use of this new technology for endovascular interventions. PMID- 22050062 TI - Combined antihypertensive and cardioprotective effects of nebivolol and hydrochlorothiazide in spontaneous hypertensive rats. AB - The antihypertensive and cardioprotective effects of the combination of nebivolol (NEB) and hydrochlorothiazide (HCTZ) in spontaneously hypertensive rats (SHR) were investigated. SHR and age-matched Wistar-Kyoto normotensive rats were randomly assigned to one of six groups: SHR treated with NEB (1 mg/kg/day, intragastric); SHR treated with HCTZ (5 mg/kg/day, intragastric); SHR treated with NEB plus HCTZ (1 + 2.5 mg/kg/day); SHR treated with NEB plus HCTZ (1 + 5 mg/kg/day), along with a SHR and a WKY control group. The effects of NEB and HCTZ on clinical chemistry parameters and on cardiac function and structure were evaluated. NEB and HCTZ in combination had synergistic antihypertensive effects and significantly reduced heart rate and blood pressure compared with monotherapy with either agent. These effects were independent of water intake, urine output and electrolyte excretion. NEB plus HCTZ was associated with reduced oxidative stress in terms of glutathione availability, lower angiotensin I levels as index of plasma renin activity and reduced clearance of urinary sodium compared with HCTZ alone. Cardiac morphometric data and antioxidant parameters indicate that NEB may influence cardiac structure by reducing hypertrophy and by enhancing the availability of endothelial nitric oxide - a unique characteristic of NEB. The authors suggest that a combination of NEB and HCTZ for the treatment of hypertension may be useful for the synergistic characteristics of both drugs. PMID- 22050064 TI - Minimally invasive video-assisted cardiac surgery: operative techniques, application fields and clinical outcomes. AB - Minimally invasive video-assisted surgery through a right minithoracotomy has become the standard surgical approach for several cardiac diseases at many major centers worldwide. In this article we review the existing literature on the subject and describe different operative techniques, application fields and clinical outcomes. PMID- 22050065 TI - Telomere length in cardiovascular disease: new challenges in measuring this marker of cardiovascular aging. AB - Atherosclerosis is an age-related systemic disease characterized by systemic oxidative stress and low grade chronic inflammation. Various types of leukocytes play an important role within this process. Telomeres, the ends of chromosomes, shorten during each and every cell division and have therefore been regarded as a cellular clock. Telomere dysfunction has been implicated in aging and senescence, and shorter leukocyte telomere length (LTL) has been demonstrated to predict cardiovascular disease and mortality. However, although LTL can predict cardiovascular events in population studies, a number of factors have prevented its broad use as a surrogate end point, such as serum levels of LDL cholesterol. In this article we will provide an overview of telomere biology and telomere dynamics of different leukocyte populations, and we will also discuss pitfalls in the methodology of LTL quantification, in context with landmark studies, which measured LTL in cardiovascular disease. Finally, we will attempt to critically assess and explain the shortcomings of LTL as a biomarker and identify further research avenues that require further investigation before telomere length can be implemented as an individual biomarker for cardiovascular aging. From this it becomes evident that LTL can be susceptible to methodological errors affecting longitudinal reproducibility. LTL is generally confounded at least by genetic factors, population variation and leukocyte composition. PMID- 22050066 TI - Kounis syndrome: a new twist on an old disease. AB - Kounis syndrome is the concurrence of acute coronary syndromes with conditions associated with mast cell activation, such as allergies or hypersensitivity and anaphylactic or anaphylactoid insults that can involve other interrelated and interacting inflammatory cells behaving as a 'ball of thread'. It is caused by inflammatory mediators such as neutral proteases including tryptase and chymase, arachidonic acid products, histamine, platelet activating factor and a variety of cytokines and chemokines released during the activation process. Platelets with FCepsilonRI and FCepsilonRII receptors also participate in the above cascade. Vasospastic allergic angina, allergic myocardial infarction and stent thrombosis with occluding thrombus infiltrated by eosinophils and/or mast cells constitute the three reported variants of this syndrome. Kounis syndrome is a ubiquitus disease that represents a magnificent natural paradigm and nature's own experiment, in a final trigger pathway implicated in cases of coronary artery spasm and plaque rupture. Kounis syndrome can complicate anesthesia, vaccination, medical therapy and stent implantation and it seems to be associated with coronary allograft vasculopathy and takotsubo syndrome, it can often be confused with hypersensitivity myocarditis and can be the cause of unexplained sudden death. Kounis syndrome has revealed that the same mediators released from the same inflammatory cells are present in acute coronary events of nonallergic etiology. These cells are not only present in the culprit region before plaque erosion or rupture but they release their contents just before an actual coronary event. Therefore, does Kounis syndrome represent a magnificent natural paradigm and nature's own experiment in a final trigger pathway implicated in cases of coronary artery spasm and plaque rupture showing a novel way towards our effort to prevent acute coronary syndromes? Drugs, substances targeting the stem cell factor that is essential for mast cell development, proliferation, survival, adhesion and homing as well as monoclonal antibodies and natural molecules that protect mast cell surface and stabilize mast cell membrane could emerge as novel therapeutic ways capable to prevent acute coronary and acute cerebrovascular events. PMID- 22050067 TI - Spinal cord stimulation for long-term treatment of severe angina pectoris: what does the evidence say? AB - Patients who continue to suffer from severe and disabling angina pectoris, despite optimum treatment in terms of conventional pharmacological therapy and/or revascularization procedures, have been termed as having refractory angina pectoris. The future group of patients with refractory angina pectoris will be different from today's patients and represent a 'moving target' as risk factors, efficacy of treatment and indications continue to change. Spinal cord stimulation (SCS) is today considered as first-line treatment of refractory angina pectoris, by the European Society of Cardiology, with an anti-ischemic effect. There is strong evidence for SCS giving symptomatic benefits (decrease in anginal attacks), improved quality of life and improvement of functional status. In addition, SCS seems to be cost effective with a 'break-even' after approximately 15-16 months. PMID- 22050068 TI - Monomorphic and polymorphic ventricular tachycardias arising from the His Purkinje system: what do we know? AB - Monomorphic and polymorphic Purkinje-related ventricular tachycardias (VTs) may occur in patients with and without underlying structural heart disease. Monomorphic Purkinje-related VTs can be divided into different entities: verapamil-sensitive left fascicular VTs; bundle branch reentry tachycardias (BBRT); interfascicular VTs and focal Purkinje VTs. The most frequent fascicular VT is left posterior fascicular VT, characterized by macro-reentry within the posterior Purkinje network. However, the reentry may also be located in the anterior Purkinje network (left anterior fascicular VT). BBRT is also a macro reentry-tachycardia, utilizing both the right and the left bundle branch as the antegrade and the retrograde limb and is often associated with pre-existing conduction disturbances in the specific conduction system. Interfascicular VT is rare and characterized by a macro-reentry within the left fascicles. BBRT and interfascicular VT may also occur in the same patient. In contrast to the mentioned macro-reentry mechanisms there are focal Purkinje-related VTs arising from the anterior or posterior Purkinje system. Focal Purkinje triggered premature ventricular contractions originating from the distal Purkinje arborization in patients without a structural heart disease, as well as in patients with known ischemic heart disease or an underlying channelopathy such as Brugada syndrome may induce polymorphic VTs. Catheter ablation is an effective treatment option for both monomorphic as well as polymorphic Purkinje-related VTs, often resulting in noninducibility and freedom from VT recurrence. A systematic analysis of the surface ECG and the intracardiac electrograms is essential for successful ablation of these heterogeneous and potentially curable VTs. PMID- 22050070 TI - Public awareness of heart attack symptoms: what should we look for and how will it help? PMID- 22050071 TI - Mapping flows of embodied emissions in the global production system. AB - Environmentally extended multiregional input-output (MRIO) analysis can be used to investigate final production and consumption attributions of emissions. As the distinction between the two attributions has been brought to the attention of policy-makers, there is an ever greater need to understand how and why they differ, by analyzing the connections between production and consumption activities. Seeking to meet this need, we present an approach for mapping flows of embodied emissions through a Leontief production system. The approach, seen as an extension of Structural Path Analysis (SPA), provides an exhaustive map of supply chain linkages between final production and consumption attributions of emissions. Whereas SPA is traditionally used to extract and rank individual supply chains according to the emissions occurring at the end of each chain, the mapping approach considers emissions embodied in the flows of intermediate products linking different economic sectors along supply chains. Illustrative results are presented from a global MRIO model and CO(2) emissions for 2004. The emissions embodied in a sector's total output of products is also of interest: a method for calculating this is presented and shown to provide further insight into where in the production system a sector's overall emissions impact is concentrated. PMID- 22050072 TI - Auriculo-condylar syndrome. AB - The auriculo-condylar syndrome is caused by abnormalities of the first and second pharyngeal arches during embryonic development. Its inheritance follows the autosomal dominant pattern. Both familial and individual cases are reported in the literature. The syndrome is characterized by wide phenotypic variation, with affected individuals expressing clinical signs of variable severity due to variable expressivity of the responsible genes. Clinical signs of the syndrome include auricular malformation, hypoplasia of the mandibular condyles, anomalies of the temporomandibular joints, malocclusion, and, in more severe cases, cleft palate, glossoptosis, facial asymmetry, and respiratory problems. The aim of this article is to report a case of a female patient with signs of the auriculo condylar syndrome and to present the pedigree of her family. Clinical findings, diagnosis, treatment plan, and final treatment are analyzed. PMID- 22050073 TI - Effects of predrilling depth and implant shape on the mechanical properties of orthodontic mini-implants during the insertion procedure. AB - OBJECTIVE: To investigate the effects of orthodontic mini-implant (OMI) shape and predrilling depth on the mechanical properties of OMIs during the insertion procedure. MATERIALS AND METHODS: A total of 30 OMIs (self-drilling type, 7 mm in length; Biomaterials Korea Inc) were allocated into six groups according to OMI shape (cylindrical and tapered type) and pre-drilling depth (control, 1.5-mm and 3.0-mm predrilling; predrilled with a drill-bit [1 mm in diameter]): C-con, C 1.5, C-3.0, T-con, T-1.5, and T-3.0 groups (N = 5 per group). The OMIs were installed in artificial bone blocks with two layers that simulated the cortical and cancellous bone (Sawbone(r), Pacific Research Laboratories Inc). Total insertion time (TIT), maximum insertion torque (MIT), total insertion energy (TIE), and inclination of the time-torque graph (INC) were measured. RESULTS: Within the same shape group, although predrilling groups exhibited shorter TIT than control groups (control vs 1.5; control vs 3.0; all P < .05), there was no difference in TIT between 1.5-mm and 3.0-mm predrilling groups. MIT and TIE decreased in the order of control, 1.5-mm predrilling, and 3.0-mm predrilling (control vs 1.5; 1.5 vs 3.0; all P < .05), but INC revealed a pattern of increase from control to 1.5-mm predrilling and of decrease from 1.5-mm predrilling to 3.0 mm predrilling within the same shape group (control vs 1.5, 1.5 vs 3.0, all P < .05). The MIT and INC of C-con were smaller and less steep than those of T-con (P < .01 and P < .05, respectively). In the same predrilling depth, no differences were observed in MIT, INC, and TIE between cylindrical and tapered groups. CONCLUSION: In cases of thick cortical bone, predrilling might be an effective tool for reducing microdamage without compromising OMI stability. PMID- 22050074 TI - Pattern formation kinetics for charged molecules on surfaces: microscopic correlation function analysis. AB - The kinetics of pattern formation and phase separation in a system of two types of oppositely charged molecules with competing short- and long-range interactions on surfaces/interfaces is studied combining three methods: a microscopic formalism of the joint correlation functions, reverse Monte Carlo, and nonequilibrium charge-screening factors. The molecular ordering occurs on the background of the Ostwald ripening and thus is strongly nonequilibrium. We have demonstrated how initial random distribution of molecules is changed for loose similar-molecule aggregates, with further reorganization into dense macroscopic domains of oppositely charged molecules. Pattern formation process is characterized by the correlation length which monotonically increases in time. PMID- 22050075 TI - Interaction between glycaemic control and serum insulin-like growth factor 1 on the risk of retinopathy in type 2 diabetes. AB - BACKGROUND: There is strong experimental evidence that insulin-like growth factor 1 (IGF-1) plays a role in the development of diabetic retinopathy. We carried out this study to determine the association between serum IGF-1 levels and retinopathy in patients with type 2 diabetes and whether this association is modified by the severity of hyperglycaemia. MATERIALS AND METHODS: A total of 480 consenting patients with type 2 diabetes were enrolled between 1 August 2001 and 31 December 2002. All participants provided a medical history and underwent a physical examination, biochemical assessment and eye fundi examination. These patients were followed up in our clinics according to our national guidelines until 31 December 2009. RESULTS: Compared with the middle tertile, increased levels of IGF-1 did not increase the risk of mild-to-moderate retinopathy (RR, 1.11; 95% CI, 0.63-1.95) and severe retinopathy (RR, 1.84; 95% CI, 0.79-8.57) at baseline. In the longitudinal analysis, increased levels of IGF-1 showed a nonsignificantly increased hazard ratio (HR) for the progression of retinopathy (HR, 1.61; 95% CI, 0.52-4.96) and severe retinopathy (HR, 1.63; 95% CI, 0.65 4.09). However, in patients with relatively good glycaemic control, there was a significantly increased risk of the progression of retinopathy (HR, 2.21; 95% CI, 1.01-5.91) and a cumulative incidence of severe retinopathy (HR, 4.82; 95% CI, 1.10-18.25) in individuals with the highest serum IGF-1 levels. CONCLUSIONS: Our data suggested serum IGF-1 was a contributing factor in severe diabetic retinopathy and this effect may be masked by poor glycaemic control. PMID- 22050076 TI - Engineering of glucose oxidase for direct electron transfer via site-specific gold nanoparticle conjugation. AB - Optimizing the electrical communication between enzymes and electrodes is critical in the development of biosensors, enzymatic biofuel cells, and other bioelectrocatalytic applications. One approach to address this limitation is the attachment of redox mediators or relays to the enzymes. Here we report a simple genetic modification of a glucose oxidase enzyme to display a free thiol group near its active site. This facilitates the site-specific attachment of a maleimide-modified gold nanoparticle to the enzyme, which enables direct electrical communication between the conjugated enzyme and an electrode. Glucose oxidase is of particular interest in biofuel cell and biosensor applications, and the approach of "prewiring" enzyme conjugates in a site-specific manner will be valuable in the continued development of these systems. PMID- 22050077 TI - The funny current (If): is it a novel antiarrhythmic target to treat atrial fibrillation? PMID- 22050078 TI - Use of other opioids during methadone therapy: a population-based study. AB - AIMS: To determine the extent to which other opioids are prescribed to patients receiving methadone in Ontario, Canada. DESIGN: Retrospective cohort study. SETTING: Ontario, Canada from 1 April 2003 to 31 March 2010. PARTICIPANTS: We studied patients aged 15-64 years with publically funded drug coverage who received at least 30 days of continuous methadone maintenance therapy (MMT). MEASUREMENTS: The proportion of patients who received more than 7 days of a non methadone opioid during MMT. A secondary analysis examined the extent to which non-methadone opioids were prescribed by physicians or dispensed by pharmacies not involved in a patient's MMT. FINDINGS: Among 18,759 patients treated with methadone, 3456 (18.4%) received at least one prescription for non-methadone opioids of more than 7 days' duration. In this group, the median number of non methadone opioid prescriptions dispensed per year was 11.9 (interquartile range 4.1-25.0). The most frequently prescribed opioids were codeine and oxycodone. Of the 73,520 non-methadone opioid prescriptions of more than 7 days' duration, nearly half (45.8%) originated from non-MMT prescribers and pharmacies. CONCLUSIONS: Many patients receiving methadone maintenance therapy in Ontario receive overlapping prescriptions for other opioids, often for extended periods. The associated prescribing patterns suggest that many such prescriptions may be duplicitous. The prescribing and dispensing of non-methadone opioids to patients receiving methadone maintenance therapy is likely to be observed in jurisdictions outside Ontario, Canada. PMID- 22050079 TI - Goodness-of-fit diagnostics for Bayesian hierarchical models. AB - This article proposes methodology for assessing goodness of fit in Bayesian hierarchical models. The methodology is based on comparing values of pivotal discrepancy measures (PDMs), computed using parameter values drawn from the posterior distribution, to known reference distributions. Because the resulting diagnostics can be calculated from standard output of Markov chain Monte Carlo algorithms, their computational costs are minimal. Several simulation studies are provided, each of which suggests that diagnostics based on PDMs have higher statistical power than comparable posterior-predictive diagnostic checks in detecting model departures. The proposed methodology is illustrated in a clinical application; an application to discrete data is described in supplementary material. PMID- 22050080 TI - The microscopic structure of adsorbed water on hydrophobic surfaces under ambient conditions. AB - The interaction of water vapor with hydrophobic surfaces is poorly understood. We utilize graphene templating to preserve and visualize the microscopic structures of adsorbed water on hydrophobic surfaces. Three well-defined surfaces [H Si(111), graphite, and functionalized mica] were investigated, and water was found to adsorb as nanodroplets (~10-100 nm in size) on all three surfaces under ambient conditions. The adsorbed nanodroplets were closely associated with atomic scale surface defects and step-edges and wetted all the hydrophobic substrates with contact angles<~10 degrees , resulting in total water adsorption that was similar to what is found for hydrophilic surfaces. These results point to the significant differences between surface processes at the atomic/nanometer scales and in the macroscopic world. PMID- 22050082 TI - Low yield of routine screening for thyroid dysfunction in asymptomatic patients with vitiligo. AB - BACKGROUND: Nonsegmental vitiligo is considered to be an autoimmune disease and is known to be associated with other autoimmune diseases, particularly affecting the thyroid. Screening patients with nonsegmental vitiligo for thyroid function and for the presence of thyroid autoantibodies has been recommended. OBJECTIVE: To investigate the prevalence of thyroid dysfunction and thyroid peroxidase specific (TPO) antibodies in a large cohort of patients with nonsegmental vitiligo in order to help decide whether routine screening is justified. METHODS: A total of 434 adults with nonsegmental vitiligo who were referred to our institute were enrolled. Thyroid function and anti-TPO antibody titres were assessed in those patients who had no history of thyroid disease or recent thyroid screening. RESULTS: Forty-three patients had already been diagnosed with thyroid dysfunction, and in 27 patients the general practitioner had performed a thyroid function test with negative results <3months previously. In these patients, thyroid function assessment was not repeated. The remaining 364 patients were screened for thyroid dysfunction. Overt hypothyroidism was newly diagnosed in three (0.8%) patients; subclinical disease was found in 10 (2.7%) patients and increased levels of TPO antibodies, without thyroid disease, were found in 49 (13.5%) patients. An elevated risk for thyroid disease was found among older women and in women with a positive family history of thyroid disease. CONCLUSION: The overall prevalence of thyroid dysfunction in adult patients with nonsegmental vitiligo was higher than reported in the general population. However, the number of newly diagnosed cases with overt and subclinical thyroid dysfunction in our population was low. Most patients had already been diagnosed by their general practitioner and had symptoms indicative for thyroid disease. Thyroid disease was found predominantly among older women and in subjects with a positive family history of thyroid disease. Thyroid screening including anti-TPO antibodies is advisable in these high-risk subpopulations. PMID- 22050083 TI - Quantification of human uridine-diphosphate glucuronosyl transferase 1A isoforms in liver, intestine, and kidney using nanobore liquid chromatography-tandem mass spectrometry. AB - Uridine-disphosphate glucuronosyl transferase (UGT) enzymes catalyze the formation of glucuronide conjugates of phase II metabolism. Methods for absolute quantification of UGT1A1 and UGT1A6 were previously established utilizing stable isotope peptide internal standards with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The current method expands upon this by quantifying eight UGT1A isoforms by nanobore high-performance liquid chromatography (HPLC) coupled with a linear ion trap time-of-flight mass spectrometer platform. Recombinant enzyme digests of each of the isoforms were used to determine assay linearity and detection limits. Enzyme expression level in human liver, kidney, and intestinal microsomal protein was determined by extrapolation from spiked stable isotope standards. Intraday and interday variability was <25% for each of the enzyme isoforms. Enzyme expression varied from 3 to 96 pmol/mg protein in liver and intestinal microsomal protein digests. Expression levels of UGT1A7, 1A8, and 1A10 were below detection limits (<1 pmol/mg protein) in human liver microsome (HLMs). In kidney microsomes the expression of UGT1A3 was below detection limits, but levels of UGT1A4, 1A7, 1A9, and 1A10 protein were higher relative to that of liver, suggesting that renal glucuronidation could be a significant factor in renal elimination of glucuronide conjugates. This novel method allows quantification of all nine UGT1A isoforms, many previously not amenable to measurement with traditional methods such as immunologically based assays. Quantitative measurement of proteins involved in drug disposition, such as the UGTs, significantly improves the ability to evaluate and interpret in vitro and in vivo studies in drug development. PMID- 22050084 TI - Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon. AB - BACKGROUND: Confluent and reticulate papillomatosis (CRP) is a rare disorder that has mostly been described in case reports and limited case series. Studies on this condition from our region are lacking. OBJECTIVE/METHODS: To describe the clinical and histopathological findings, as well as response to treatment of all patients diagnosed with CRP at the American University of Beirut Medical Center (AUB-MC) between 1999 and 2009, and to compare our findings with those published in the literature. RESULTS: Confluent and reticulate papillomatosis was diagnosed in 10 patients (five men, five women). Mean age at diagnosis was 19 years. Duration of lesions ranged from few months to several years. Skin lesions mainly consisted of reticulated, pigmented macules, patches and plaques. The most common area of involvement was the chest in five cases. The rash was asymptomatic in eight patients. Skin biopsy specimens from all patients revealed hyperkeratosis, papillomatosis and variable acanthosis. Whereas follicular plugging was observed in nine cases, anastomosis of the rete ridges was noted in three. Periodic acid Schiff stains highlighted yeast forms in six cases. CONCLUSION: The clinical and histopathological features of the CRP patients in our study are generally comparable to those published in the literature, with minor differences. Clinically, one case had an atypical clinical presentation, and microscopically follicular plugging was seen in the majority of cases. Yeast-like spores were seen in six cases further supporting a role of Malassezia furfur in the pathogenesis of CRP. PMID- 22050085 TI - Reversed binding of a small molecule ligand in homologous chemokine receptors - differential role of extracellular loop 2. AB - BACKGROUND AND PURPOSE: The majority of small molecule compounds targeting chemokine receptors share a similar pharmacophore with a centrally located aliphatic positive charge and flanking aromatic moieties. Here we describe a novel piperidine-based compound with structural similarity to previously described CCR8-specific agonists, but containing a unique phenyl-tetrazol moiety which, in addition to activity at CCR8 was also active at CCR1. EXPERIMENTAL APPROACH: Single point mutations were introduced in CCR1 and CCR8, and their effect on small molecule ligand-induced receptor activation was examined through inositol trisphosphate (IP(3) ) accumulation. The molecular interaction profile of the agonist was verified by molecular modeling. KEY RESULTS: The chemokine receptor conserved glutamic acid in TM-VII served as a common anchor for the positively charged amine in the piperidine ring. However, whereas the phenyl tetrazol group interacted with TyrIV:24 (Tyr(172) ) and TyrIII:09 (Tyr(114) ) in the major binding pocket (delimited by TM-III to VII) of CCR8, it also interacted with TrpII:20 (Trp(90) ) and LysII:24 (Lys(94) ) in the minor counterpart (delimited TM-I to III, plus TM-VII) in CCR1. A straightening of TM-II by Ala substitution of ProII:18 confirmed its unique role in CCR1. The extracellular loop 2 (ECL-2) contributed directly to the small molecule binding site in CCR1, whereas it contributed to efficacy, but not potency in CCR8. CONCLUSION AND IMPLICATIONS: Despite high ligand potency and efficacy and receptor similarity, this dual-active and bitopic compound binds oppositely in CCR1 and CCR8 with different roles of ECL-2, thereby expanding and diversifying the influence of extracellular receptor regions in drug action. PMID- 22050086 TI - Confidential enquiry into perioperative equine fatalities: CEPEF 4--a chance to gain new evidence about the risks of equine general anaesthesia. PMID- 22050087 TI - Theory and simulation of angular hysteresis on planar surfaces. AB - A simple model is proposed to simulate contact angle hysteresis in drops on a planar surface. The model is based on assuming a friction force acting on the triple contact line in such a way that the contact line keeps fixed for contact angles comprised between the advancing angle and the receding one and is allowed to move in order to avoid angles outside this interval. The model is straightforwardly applied to axisymmetric drops for which a simple solution of the Young-Laplace equation can be obtained. A variation of the method has also been implemented for nonaxisymmetric drops by resorting to the public-domain "Surface Evolver" software. Comparison with experiments shows the excellent performance of the model. PMID- 22050089 TI - Perineuriomatous melanocytic nevi. PMID- 22050090 TI - Shana and james. PMID- 22050091 TI - Use of classic and novel immunohistochemical markers in the diagnosis of cutaneous myeloid sarcoma. AB - Cutaneous myeloid sarcoma is often challenging to diagnose based solely upon histopathological features. Although immunohistochemistry can aid in its diagnosis, specific markers have not been clearly identified. We evaluated the utility of immunohistochemical markers in 57 cutaneous myeloid sarcoma cases. In addition to classical markers (CD117, CD163, CD34, myeloperoxidase and lysozyme), we used CD33 and CD14, recently described markers in paraffin-embedded tissue samples, and Kruppel-like factor 4 (KLF-4), a novel monocytic marker. Our results show that lysozyme was expressed in 91%, CD33 in 60%, myeloperoxidase in 54%, CD34 in 39% and CD117 in 36% of cases. An antibody panel that included lysozyme, CD117 and CD33 identified all cases. The monocytic markers CD14, KLF-4 and CD163 were expressed in 60, 58 and 40% of all cases, respectively. CD14 and KLF-4 expression was significantly more common in cases with monocytic differentiation. CD14 is the single most sensitive and specific marker for monocytic differentiation (79 and 80%). Although KLF-4 in isolation is relatively insensitive (50 and 87%), it enhances sensitivity in detecting monocytic cutaneous myeloid sarcoma when combined with CD14. Our results indicate that in addition to classical immunohistochemical markers, targeted use of newer antibodies, including CD33, CD14 and KLF-4 is useful in the diagnosis of cutaneous myeloid sarcoma and in the detection of monocytic differentiation. PMID- 22050092 TI - Aberrant Melan-A expression in atypical fibroxanthoma and undifferentiated pleomorphic sarcoma of the skin. AB - BACKGROUND: Atypical fibroxanthoma (AFX) is a distinctive clinicopathologic entity presenting on sun-damaged skin of the elderly. Its behavior is benign if strict diagnostic criteria are applied. Tumors showing invasion of deeper structures or perineural/lymphovascular invasion are best regarded as undifferentiated pleomorphic sarcoma of the skin. The diagnosis requires immunohistochemical studies to exclude melanoma, squamous cell carcinoma, angiosarcoma and leiomyosarcoma. METHODS: Two AFX and one undifferentiated pleomorphic sarcoma showing aberrant expression of Melan-A were identified. Clinical data were obtained and histopathological features, immunohistochemical profile and electron microscopy were assessed. RESULTS: All tumors arose on sun damaged skin of elderly males. Two AFX showed pushing growth into superficial subcutis only. The undifferentiated pleomorphic sarcoma was characterized by infiltrative growth into galea as well as perineural invasion. Multifocal expression of Melan-A and MART-1 was largely limited to tumor giant cells in the absence of S100 or HMB-45 labeling. No melanosomes or premelanosomes were identified by electron microscopy. CONCLUSIONS: Aberrant expression of Melan-A and MART-1 in AFX and undifferentiated pleomorphic sarcoma of the skin represents an important diagnostic pitfall with potential for misdiagnosis as melanoma. PMID- 22050093 TI - Angiosarcoma: a study of 98 cases with immunohistochemical evaluation of TLE3, a recently described marker of potential taxane responsiveness. AB - Angiosarcomas may be primary in the skin, primary in soft tissue or viscera, or secondary to irradiation. All angiosarcomas have a poor prognosis. Taxanes may have efficacy in the treatment of angiosarcoma. Expression of TLE3 has been associated with improved outcome in taxane-treated breast cancers. We studied a series of angiosarcoma with TLE3 immunohistochemistry. Cases of angiosarcoma (98 total cases; 37 cutaneous, 48 soft tissue/visceral and 13 post-irradiation) were retrieved and follow up was obtained. Tumors were classified as 'vasoformative', 'spindled', 'epithelioid' and 'mixed'. TLE3 immunohistochemistry was performed. Statistical analyses were performed. Patients (50 males and 48 females) had a median age of 60.2 years. Tumors had a median size 7.5 cm and were vasoformative (N = 43, 44%), spindled (N = 21, 21%), epithelioid (N = 16, 16%) and mixed (N = 18, 18%). Follow up was available for 89/98 patients (91%): 32 (36%) were dead due to disease, 36 (41%) were dead due to other causes and 21 (24%) remained alive. The median time to death was 2.1 years. TLE3 reactivity was observed in 0/37 (0%) cutaneous angiosarcomas, in 28/48 (58%) cases from soft tissue/viscera and in 4/13 (31%) post-irradiation angiosarcomas. (p = <0.0001). Improved 5-year survival was seen in vasoformative angiosarcomas (p = 0.03). TLE3 expression was not associated with taxane response. However, only a subset of patients was treated with taxane. Our study confirms the poor prognosis of angiosarcoma. Vasoformative angiosarcoma may have a more favorable prognosis. A lack of TLE3 expression in cutaneous angiosarcoma may reflect differing pathogenesis. PMID- 22050094 TI - Perforin and granzyme B expression in oral and cutaneous lichen planus - a comparative study. AB - BACKGROUND: Although cutaneous and oral lichen planus (LP) share similar histopathological features, oral LP often follows a recalcitrant course while LP skin lesions tend to be self-limiting. Apoptosis, mediated by cytotoxic T-cells in LP, may be triggered by the release of molecules such as perforin and granzyme B. As variation in clinical behavior can reflect differences in LP immune expression, we studied the role of those cytotoxic molecules in oral and cutaneous LP. METHODS: We analyzed 16 cases of cutaneous LP and 29 of oral LP. The sections were studied on hematoxylin and eosin, CD4, CD8, perforin and granzyme B staining. RESULTS: The mean number of immunostained cells expressing each cytotoxic molecule was significantly higher in oral LP than in cutaneous LP. A higher number of single necrotic keratinocytes (apoptotic bodies) was found in oral LP lesions when compared to cutaneous LP. Only in oral LP lesions, a higher number of CD4-positive cells was found in active lesions when compared to regressive lesions. CONCLUSIONS: Our results confirm increased expression of granzyme B and perforin in oral LP lesions as compared to cutaneous LP. The increased expression suggests a relationship with the clinical behavior of the disease. PMID- 22050096 TI - My cup runneth over: young people's lack of knowledge of low-risk drinking guidelines. AB - INTRODUCTION AND AIMS: If young people are to consume alcohol in accordance with government guidelines, they must possess the relevant knowledge and skills. No previous research has examined correlations between different forms of knowledge of alcohol guidelines or how they are related to personality variables and beliefs. DESIGN AND METHODS: Two samples were recruited in South-East England: 309 secondary school students aged 16-18, and 125 university students aged 18-25. All participants completed a computer-administered survey of knowledge and beliefs. University students also reported their alcohol consumption and completed tasks in which they poured their 'usual' drinks, and what they believed to be 'units' of alcohol. RESULTS: Most respondents lacked the knowledge and skills required to drink in accordance with government guidelines. Participants' usual drinks were substantially larger than one unit, and participants tended to underestimate the unit content of drinks. There was little evidence that possession of accurate knowledge of one aspect of alcohol units and guidelines was related to accurate knowledge in other domains. DISCUSSION AND CONCLUSIONS: Many young people may lack the knowledge required to monitor their alcohol consumption or give accurate self-reports in research. Future research should evaluate using a drink-pouring task as part of interventions designed to improve knowledge and skills and encourage moderate consumption of alcohol. PMID- 22050097 TI - Long-term culture and cryopreservation of interstitial cells of Cajal. AB - OBJECTIVE: Interstitial cells of Cajal (ICCs) in the gastrointestinal tract generate and propagate slow waves and mediate neuromuscular neurotransmission. Damage to ICCs has been described in several gastrointestinal motor disorders, and although many studies have examined ICCs in culture, they have been largely limited to freshly dissociated cells or short-term cultures. An efficient and reliable method to establish a source of ICCs is much needed. The aim of this study was to investigate methods for culturing, subculturing, cryopreservation, and recovery of ICCs. METHODS: ICCs were derived from intestinal segments of domestic rabbits, and immunohistochemistry for c-Kit was used to identify ICCs in culture and after recovery. Recovered ICCs were also examined for motilin receptor expression. RESULTS: Optimal conditions for ICC culture and cryopreservation were based on cell growth curves and MTT assay. On the basis of these findings, recovered cells were cultured for 7 days and then sorted via flow cytometry based on c-Kit immunoreactivity. The percent of c-Kit positive cells was 64.3%, and the number of ICCs sorted was 6.7 * 10(5). Reverse-transcription polymerase chain reaction and western blotting verified motilin receptor expression in c-Kit-positive ICCs. CONCLUSIONS: This is the first study to describe the culture, passage, and recovery of ICCs and to show motilin receptor expression. Our results suggest that ICCs play an important role, at least in some species, in initiating the migrating myoelectric complex induced by motilin. PMID- 22050108 TI - Maximal accumulated oxygen deficit in running and cycling. AB - The purpose of this study was to compare values of maximal accumulated oxygen deficit (MAOD; a measure of anaerobic capacity) in running and cycling. Twenty seven women and 25 men performed exhaustive treadmill and cycle ergometer tests of ~3 min, ~5 min, and ~7 min duration. Oxygen demands were estimated assuming a linear relationship between demand and intensity and also using upwardly curvilinear relationships. When oxygen demand was estimated using speed (with exponent 1.05), values for MAOD for the three running tests were virtually identical; the mean of the three values was 78 +/- 7 mL.kg-1. Use of an oxygen demand that was estimated using work rate (with exponent 1.00) generated the most similar values for MAOD from the three cycling tests (mean of 59 +/- 6 mL.kg-1). Consistent with the higher (p < 0.05) MAOD in running, peak post-exercise blood lactate concentrations were also higher (p < 0.05) in running (13.9 +/- 2.2 mmol.L-1) than in cycling (12.6 +/- 2.4 mmol.L-1). The results suggest that the relationship between oxygen demand and running speed is upwardly curvilinear for the speeds used to measure MAOD; the relationship between demand and cycle ergometer work rate is linear; MAOD is greater in running than in cycling. PMID- 22050109 TI - Nonadiabatic quantum chemistry--past, present, and future. PMID- 22050111 TI - Covalent stabilization: a sturdy molecular square from reversible metal-ion directed self-assembly. AB - Supramolecular self-assembly using weak interactions under quasi-equilibrium conditions has provided easy access to very complex but often quite fragile molecules. We now show how a labile structure obtained from reversible transition metal-directed self-assembly of rods and connectors serves as a template that can be converted into a sturdy structure of identical topology and similar geometry. The process consists of Cu(I)-catalyzed replacement of all rods or connectors terminated with pyridines for analogues terminated with ethynyls, converting dative N->Pt(+) bonds into covalent C-Pt bonds. The procedure combines the facility and high yield of reversible self-assembly with the robustness of covalent synthesis. PMID- 22050116 TI - Understanding the equilibrium ion exchange properties in faujasite zeolite from Monte Carlo simulations. AB - We have adapted a grand ensemble Monte Carlo simulation method to directly compute, for the first time to our knowledge, univalent cation exchange isotherms in zeolites. The computed isotherms for the exchange of sodium in NaY faujasite by lithium, potassium, rubidium, and cesium ions, respectively, are in good agreement with the experimental ones. They display the three main types of behavior observed in zeolites, namely, a monotonous evolution of selectivity throughout the exchange process (Li(+)), a selectivity reversal (K(+)), and an incomplete exchange (Rb(+) and Cs(+)). The initial stage of the cation exchange is shown to be dominated by the hydration energy of the cations in the external aqueous solution. The final part of the process is often dominated by the cation framework and cation-cation interactions. A crossover between these two regimes explains the frequently observed reversal of selectivity phenomenon. The incomplete exchange observed in the case of Rb(+) and Cs(+) is shown to correspond to a blocked state of the system for highest accessible composition of the aqueous solution. This stable state is shown not to be linked to an inability of the cesium cations to cross the six-ring window in order to penetrate into the smallest cages. PMID- 22050114 TI - A seven country comparison of nurses' perceptions of their professional practice environment. AB - Papastavrou E., Efstathiou G., Acaroglu R., da Luz M.D.A., Berg A., Idvall E., Kalafati M., Kanan N., Katajisto J., Leino-Kilpi H., Lemonidou C., Sendir M., Sousa V.D. & Suhonen R. (2011) Journal of Nursing Management A seven country comparison of nurses' perceptions of their professional practice environment Aims To describe and compare nurses' perceptions of their professional practice environment in seven countries. Background There is evidence of variation in the nursing professional practice environments internationally. These different work environments affect nurses' ability to perform and are linked to differing nurse and patient outcomes. Methods A descriptive, comparative survey was used to collect data from orthopaedic and trauma nurses (n = 1156) in Finland, Cyprus, Greece, Portugal, Sweden, Turkey and Kansas, USA using the 39-item Revised Professional Practice Environment instrument. Results Differences were found between participants from the northern countries of Europe, Kansas, USA, and the Mediterranean countries regarding perceptions about control over practice. No between-country differences were reported in the internal work motivation among the nurses from any of the participating countries. Conclusions Although between country differences in nurses' professional practice environment were found, difficulties related to demographic, cultural and health system differences and the way in which nursing is defined in each country need to be considered in the interpretation of the results. Implications for Nursing Management The results support investment to improve nurse's work environment, which is important for improving the quality of patient care, optimizing patient outcomes and developing the nursing workforce. PMID- 22050117 TI - Chemically isolated graphene nanoribbons reversibly formed in fluorographene using polymer nanowire masks. AB - We demonstrated the fabrication of graphene nanoribbons (GNRs) as narrow as 35 nm created using scanning probe lithography to deposit a polymer mask(1-3) and then fluorinating the sample to isolate the masked graphene from the surrounding wide band gap fluorographene. The polymer protected the GNR from atmospheric adsorbates while the adjacent fluorographene stably p-doped the GNRs which had electron mobilities of ~2700 cm2/(V.s). Chemical isolation of the GNR enabled resetting the device to nearly pristine graphene. PMID- 22050115 TI - Ultrafast photophysics of the isolated indole molecule. AB - The relaxation dynamics of the isolated indole molecule has been tracked by femtosecond time-resolved ionization. The excitation region explored (283-243 nm) covers three excited states: the two pipi* L(b) and L(a) states, and the dark pisigma* state with dissociative character. In the low energy region (lambda > 273 nm) the transients collected reflect the absorption of the long living L(b) state. The L(a) state is met 1000-1500 cm(-1) above the L(b) origin, giving rise to an ultrafast lifetime of 40 fs caused by the internal conversion to the lower L(b) minimum through a conical intersection. An additional ~400 fs component, found at excitation wavelengths shorter than 263 nm, is ascribed to dynamics along the pisigma* state, which is likely populated through coupling to the photoexcited L(a) state. The study provides a general view of the indole photophysics, which is driven by the interplay between these three excited surfaces and the ground state. PMID- 22050120 TI - Cu(bipy)2+/TEMPO-catalyzed oxidation of alcohols: radical or nonradical mechanism? AB - In the oxidation of alcohols with TEMPO as catalyst, the substrate has alternatively been postulated to be oxidized but uncoordinated TEMPO(+) (Semmelhack) or Cu-coordinated TEMPO(*) radical (Sheldon). The reaction with the Cu(bipy)(2+)/TEMPO cocatalyst system has recently been claimed, on the basis of DFT calculations, to not be a radical reaction but to be best viewed as electrophilic attack on the alcohol C-H(alpha) bond by coordinated TEMPO(+). This mechanism combines elements of the Semmelhack mechanism (oxidation of TEMPO to TEMPO(+)) and the Sheldon proposal ("in the coordination sphere of Cu"). The recent proposal has been challenged on the basis of DFT calculations with a different functional, which were reported to lead to a radical mechanism. We carefully examine the results for the two functionals and conclude from both the calculated energetics and from an electronic structure analysis that the results of the two DFT functionals are consistent and that both lead to the proposed mechanism with TEMPO not acting as radical but as (coordinated) positive ion. PMID- 22050119 TI - Research needs grants, funding and money--missing something? PMID- 22050112 TI - Risk for permanent pacemaker after transcatheter aortic valve implantation: a comprehensive analysis of the literature. AB - BACKGROUND: Permanent pacemaker (PM) requirement is a known complication after transcatheter aortic valve implantation (TAVI). There are, however, no systematic data concerning this complication. OBJECTIVE: To determine the incidence and potential predictors of permanent PM requirement after TAVI based on published literature. METHODS: We conducted a MEDLINE search to identify potentially relevant literature dealing with PM requirement after TAVI. Data were collected on paper extraction forms by 2 independent investigators. RESULTS: There were 32 relevant published studies comprising data of 5,258 patients without an implanted PM before TAVI. An Edwards-Sapiens(r) prosthesis (ESP) was implanted in 2,887 patients, whereas 2,371 patients received a CoreValve(r) prosthesis (CVP). The crude incidence of PM implantation after TAVI was 15%. Six hundred and fourteen of 2,371 (25.8%) CVP patients and 189 of the 2,887 (6.5%) ESP patients had to receive a permanent PM (odds ratio [OR] 4.91, 95% confidence interval [CI] 4.12 5.86, P < 0.001). Presence of right bundle branch block (RBBB) before TAVI was a significant predictor for development of complete atrioventricular (AV) block and subsequent PM need (OR 1.358, 95% CI 1.001-1.841, P = 0.02). More than 90% of all AV-block requiring PM implantation occurred immediately or within 7 days after TAVI. CONCLUSION: Patients undergoing TAVI with implantation of CVP are at significantly higher risk for development of AV block and subsequent need for permanent PM, particularly if RBBB preexists. Since AV block occurs in >90% within the first week after the procedure, careful monitoring should be performed for at least 7 days after TAVI. PMID- 22050110 TI - Clinical significance of steroid and xenobiotic receptor and its targeted gene CYP3A4 in human prostate cancer. AB - The steroid and xenobiotic receptor (SXR) regulates cytochrome P450 (CYP) enzymes, which are key inactivators of testosterone in the liver and prostate. In the present study, we investigated SXR expression in human prostate tissues. We determined SXR immunoreactivity using an anti-SXR antibody in benign (n = 78) and cancerous (n = 106) tissues obtained by radical prostatectomy. Stained slides were evaluated for the proportion and staining intensity of immunoreactive cells. Total immunoreactivity (IR) scores (range: 0-8) were calculated as the sum of the proportion and intensity scores. Associations between the clinicopathological features of the patients, SXR status, and CYP3A4 immunoreactivity were analyzed. Western blot analyses validated the specificity of the anti-SXR antibody in 293T cells transfected with pcDNA-FLAG-SXR. Positive (IR score: >= 2) nuclear SXR staining was observed in 91% (71/78) of benign foci and 47% (50/106) of cancerous lesions. Immunoreactivity scores were significantly lower in the cancerous lesions than in the benign foci (P < 0.0001). Clinicopathological analyses showed that cancer-specific survival in patients with high SXR IR scores (>= 4) was significantly increased (P = 0.046). Combined data of present and previous studies showed that high IR scores for both the SXR and CYP3A4 correlated with significantly better cancer-specific survival rates in multivariate regression analyses (hazard ratio: 2.15, 95% confidence interval: 1.25-3.55, P = 0.007). We showed differential SXR expression in human prostate tissues. The high expression of the SXR and CYP3A4 is a strong prognostic indicator of favorable outcomes in prostate cancer, and could be a therapeutic target. PMID- 22050113 TI - Anti-alpha actinin antibodies as new predictors of response to treatment in autoimmune hepatitis type 1. AB - BACKGROUND: We reported that combined presence of autoantibodies (Abs) against filamentous-actin (AFA) and alpha-actinin are specific for autoimmune hepatitis type 1 (AIH-1) diagnosis. AIM: To explore our data and assess whether anti-alpha actinin and AFA Abs could be used as indicators of response to treatment and predictors of AIH-1 flares in a large cohort of AIH-1 patients. METHODS: Seven hundred and sixty-four serial serum samples of 86 consecutive AIH-1 patients, 509 pathological and 110 normal controls were tested for the presence of anti-alpha actinin and AFA Abs by an in-house IgG-specific ELISA and a standardised commercially available ELISA respectively. Patients sera were divided into baseline group (active disease before treatment initiation, n = 86) and then according to treatment response into group A-responders (n = 40 patients), group B-relapsers/incomplete responders (n = 37 patients) and group C-not-treated (n = 9 patients). RESULTS: Anti-alpha-actinin and AFA levels were significantly higher at baseline. Double reactivity against alpha-actinin and AFA was associated with disease activity (OR 4.9; 95% CI: 2.7-9). Anti-alpha-actinin optical densities (ODs) before treatment decreased significantly at first remission (P < 0.05). Treatment response was associated with anti-alpha-actinin Abs negativity before treatment (OR 3.4; 95% CI: 1.3-8.9) and absence of double positivity for anti alpha-actinin and AFA Abs before treatment (OR 3.8; 95% CI: 1.4-10.4). Responders had lower baseline levels of anti-alpha-actinin than relapsers and/or incomplete responders (P = 0.002). Binary logistic regression revealed lower levels of anti alpha-actinin as the only independent predictors of response (P = 0.05). CONCLUSIONS: Anti-alpha-actinin Abs at baseline appear to predict treatment response and therefore they might be used for monitoring treatment outcome in AIH 1. PMID- 22050118 TI - Modeling functional data with spatially heterogeneous shape characteristics. AB - We propose a novel class of models for functional data exhibiting skewness or other shape characteristics that vary with spatial or temporal location. We use copulas so that the marginal distributions and the dependence structure can be modeled independently. Dependence is modeled with a Gaussian or t-copula, so that there is an underlying latent Gaussian process. We model the marginal distributions using the skew t family. The mean, variance, and shape parameters are modeled nonparametrically as functions of location. A computationally tractable inferential framework for estimating heterogeneous asymmetric or heavy tailed marginal distributions is introduced. This framework provides a new set of tools for increasingly complex data collected in medical and public health studies. Our methods were motivated by and are illustrated with a state-of-the art study of neuronal tracts in multiple sclerosis patients and healthy controls. Using the tools we have developed, we were able to find those locations along the tract most affected by the disease. However, our methods are general and highly relevant to many functional data sets. In addition to the application to one dimensional tract profiles illustrated here, higher-dimensional extensions of the methodology could have direct applications to other biological data including functional and structural magnetic resonance imaging (MRI). PMID- 22050128 TI - Surface faceting dependence of thermal transport in silicon nanowires. AB - Surface faceting on sidewalls is ubiquitously observed during crystal growth of semiconductor nanowires. However, predicting the thermal transport characteristics of faceted nanowires relevant to thermoelectric applications remains challenging. Here, direct molecular dynamics simulations show that thermal conductivity is considerably reduced in crystalline <111> Si nanowires with periodic sawtooth faceting compared to nanowires of same size with smooth sidewalls. It is discovered that surface phonon scattering is particularly high with {100} facets, but less pronounced with {113} facets and remarkably low with {111} facets, which suggests a new means to optimize phonon dynamics for nanoscale thermoelectric devices. This anomaly is reconciled by showing that the contribution of each facet to surface phonons is due to diffuse scattering rather than to backward scattering. It is further shown that this property is not changed by addition of an amorphous shell to the crystalline core, similar to the structure of experimental nanowires. PMID- 22050125 TI - Effects of the ruminal comminution rate and microbial contamination of particles on accuracy of in situ estimates of ruminal degradability and intestinal digestibility of feedstuffs. AB - Effects of considering the comminution rate (k(c) ) and the correction of microbial contamination (using (15) N techniques) of particles in the rumen on estimates of ruminally undegraded fractions and their intestinal digestibility were examined generating composite samples (from rumen-incubated residues) representative of the undegraded feed rumen outflow. The study used sunflower meal (SFM) and Italian ryegrass hay (RGH) and three rumen and duodenum cannulated wethers fed with a 40:60 RGH to concentrate diet (75 g DM/kgBW(0.75) ). Transit studies up to the duodenum with Yb-SFM and Eu-RGH marked samples showed higher k(c) values (/h) in SFM than in RGH (0.577 vs. 0.0892, p = 0.034), whereas similar values occurred for the rumen passage rate (k(p) ). Estimates of ruminally undegraded and intestinal digestibility of all tested fractions decreased when k(c) was considered and also applying microbial correction. Thus, microbial uncorrected k(p) -based proportions of intestinal digested undegraded crude protein overestimated those corrected and k(c) -k(p) -based by 39% in SFM (0.146 vs. 0.105) and 761% in RGH (0.373 vs. 0.0433). Results show that both k(c) and microbial contamination correction should be considered to obtain accurate in situ estimates in grasses, whereas in protein concentrates not considering k(c) is an important source of error. PMID- 22050123 TI - Copper quantum clusters in protein matrix: potential sensor of Pb2+ ion. AB - A one-pot synthesis of extremely stable, water-soluble Cu quantum clusters (QCs) capped with a model protein, bovine serum albumin (BSA), is reported. From matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, we assign the clusters to be composed of Cu(5) and Cu(13) cores. The QCs also show luminescence properties having excitation and emission maxima at 325 and 410 nm, respectively, with a quantum yield of 0.15, which are found to be different from that of protein alone in similar experimental conditions. The quenching of luminescence of the protein-capped Cu QCs in the presence of very low hydrogen peroxide concentration (approximately nanomolar, or less than part per-billion) reflects the efficacy of the QCs as a potential sensing material in biological environments. Moreover, as-prepared Cu QCs can detect highly toxic Pb(2+) ions in water, even at the part-per-million level, without suffering any interference from other metal ions. PMID- 22050124 TI - Dynamic measurements of mitochondrial hydrogen peroxide concentration and glutathione redox state in rat pancreatic beta-cells using ratiometric fluorescent proteins: confounding effects of pH with HyPer but not roGFP1. AB - Using the ROS (reactive oxygen species)-sensitive fluorescent dyes dichlorodihydrofluorescein and dihydroethidine, previous studies yielded opposite results about the glucose regulation of oxidative stress in insulin-secreting pancreatic beta-cells. In the present paper, we used the ratiometric fluorescent proteins HyPer and roGFP1 (redox-sensitive green fluorescent protein 1) targeted to mitochondria [mt-HyPer (mitochondrial HyPer)/mt-roGFP1 (mitochondrial roGFP1)] to monitor glucose-induced changes in mitochondrial hydrogen peroxide concentration and glutathione redox state in adenovirus-infected rat islet cell clusters. Because of the reported pH sensitivity of HyPer, the results were compared with those obtained with the mitochondrial pH sensors mt-AlpHi and mt SypHer. The fluorescence ratio of the mitochondrial probes slowly decreased (mt HyPer) or increased (mt-roGFP1) in the presence of 10 mmol/l glucose. Besides its expected sensitivity to H2O2, mt-HyPer was also highly pH sensitive. In agreement, changes in mitochondrial metabolism similarly affected mt-HyPer, mt AlpHi and mt-SypHer fluorescence signals. In contrast, the mt-roGFP1 fluorescence ratio was only slightly affected by pH and reversibly increased when glucose was lowered from 10 to 2 mmol/l. This increase was abrogated by the catalytic antioxidant Mn(III) tetrakis (4-benzoic acid) porphyrin but not by N-acetyl-L cysteine. In conclusion, due to its pH sensitivity, mt-HyPer is not a reliable indicator of mitochondrial H2O2 in beta-cells. In contrast, the mt-roGFP1 fluorescence ratio monitors changes in beta-cell mitochondrial glutathione redox state with little interference from pH changes. Our results also show that glucose acutely decreases rather than increases mitochondrial thiol oxidation in rat beta-cells. PMID- 22050122 TI - The effect of green tea polyphenols on macrophage migration inhibitory factor associated steroid resistance. AB - BACKGROUND: Recently, evidence has been obtained to suggest that inflammation is provoked through upregulation of macrophage migration inhibitory factor (MIF) expression by steroids. However, little is known regarding the effect of steroids on MIF expression in human keratinocytes and the counter-effect of epigallocatechin-3-gallate (EGCG), a member of the class of green tea polyphenols. OBJECTIVES: We determined whether or not steroids cause the upregulation of MIF in human keratinocytes, and if so, whether or not EGCG suppresses MIF upregulation in keratinocytes by steroids. We then assessed the effects of EGCG on MIF-induced Th-related chemokine and cytokine expression in keratinocytes. METHODS: HaCaT keratinocytes were first treated with dexamethasone in the presence or absence of EGCG in the culture medium. The keratinocytes were then treated with recombinant human (rh)-MIF in the presence or absence of EGCG in the culture medium. The expression of mRNA and protein in Th-related cytokines and chemokines, including MIF in the keratinocytes, was measured by real-time reverse transcription-polymerase chain reaction, Western blotting and enzyme linked immunosorbent assay. RESULTS: Dexamethasone significantly enhanced MIF expression in human keratinocytes, and EGCG significantly downregulated the expression of dexamethasone-induced MIF. EGCG also significantly downregulated rh MIF-induced expression of Th-related cytokines and chemokines, such as interleukin (IL)-6, IL-18, transforming growth factor-beta, CCL17, CCL22 and CXCL10, in human keratinocytes. CONCLUSIONS: These results demonstrated that EGCG may have a novel pharmacological effect to prevent steroid-induced tachyphylaxis and inflammation by suppressing the expression of MIF in human keratinocytes. PMID- 22050129 TI - Molecular structure encodes nanoscale assemblies: understanding driving forces in electrostatic self-assembly. AB - Supramolecular nanoparticles represent a key field in recent research as their synthesis through self-assembly is straightforward and they often can respond to external triggers. A fundamental understanding of structure-directing factors is highly desirable for a targeted structure design. This contribution demonstrates a quantitative relation between the size of supramolecular self-assembled nanoparticles and the free energy of association. Nanoparticles are prepared by electrostatic self-assembly of cationic polyelectrolyte dendrimers as model macroions and oppositely charged di- and trivalent organic dye molecules relying on the combination of electrostatic and pi-pi-interactions. A systematic set of sulfonate-group carrying azo-dyes was synthesized. Light scattering and zeta potential measurements on the resulting nanoparticles yield hydrodynamic radii between 20 nm < R(H) < 50 nm and positive zeta-potential values indicating a positive particle charge. Studies on dye self-aggregation and dendrimer-dye association by isothermal titration calorimetry (ITC) and UV-vis spectroscopy allow for the correlation of the thermodynamic parameters of dendrimer-dye association with the size of the particles, showing that at least a free energy gain of DeltaG ~ - 32 kJ mol(-1) is necessary to induce dendrimer interconnection. Structural features of the azo dyes causing these to favor or prevent nanoparticle formation have been identified. The dye-dye-interaction was found to be the key factor in particle size control. A simple model yields a quantitative relation between the free energy and the particle sizes, allowing for predicting the latter based on thermodynamic measurements. Hence, a set of different molecular "building bricks" can be defined where the choice of building block determines the resulting assembly size. PMID- 22050130 TI - A questionnaire study on parasite control practices on UK breeding Thoroughbred studs. AB - REASONS FOR PERFORMING STUDY: Improved education of veterinarians and equine owners/managers is essential in implementing parasite control strategies that are less reliant on chemicals. METHODS: This questionnaire study, conducted on 61 UK Thoroughbred (TB) establishments during 2009 and 2010, was designed to obtain an understanding of current helminth control practices on studs. To our knowledge, this is the first occasion that statements obtained from TB studs via questionnaire have been supported by statistical analysis. RESULTS: Despite many respondents indicating high levels of concern regarding anthelmintic resistance, 56% of these establishments that received visiting equines co-grazed these animals with permanent stock and <74% administered anthelmintics prior to integration. In the 12 months preceding the study, most respondents administered frequent macrocyclic lactone (ML) treatments, with none appearing to leave any animals in groups untreated at each administration. Indiscriminate whole group treatments with MLs and movement of animals to 'clean grazing' post treatment (reported by >25% of respondents), indicates that many stud owners/managers are not aware of the strong risk factors for the development of anthelmintic resistance. Few studs had conducted faecal egg count (FEC) analysis in the past and only 22% indicated that they considered this form of analysis beneficial in determining anthelmintic choice. CONCLUSIONS AND POTENTIAL RELEVANCE: The challenge now is to convince stud owners/managers to deviate from their current practices to control strategies that are more likely to preserve anthelmintic efficacy. Veterinarians need to get more involved in implementing these control strategies, with better emphasis placed on the role of diagnostic tests in facilitating targeted treatments and in investigating anthelmintic sensitivity in the associated nematode populations. PMID- 22050135 TI - IBS: transforming our governance. AB - After more than 60 years, the Legislative Council overwhelming approved a revised governance structure for the International Biometric Society (IBS) to take effect from 1 January 2012. Responsibility for the governance and leadership of the society will be combined and placed in the hands of an Executive Board, supported by a much larger Representative Council. The Representative Council will be composed of members selected by the different regions (or geographical components) of the society. It will be responsible for overseeing the nomination and election (by the whole society) of the Executive Board and provide the conduit between the regions and this leadership team. Members of the Representative Council will also chair the Standing Committees. The transition process to the new governance structure is outlined, as are focus issues for the next decade. PMID- 22050132 TI - The effect of sports specialization on musculus quadriceps function after exercise-induced muscle damage. AB - The primary aim of the present study was to examine the effect of eccentric exercise-induced (100 submaximal eccentric contractions at an angular velocity of 60 degrees s-1, with 20-s rest intervals) muscle damage on peripheral and central fatigue of quadriceps muscle in well-trained long-distance runners, sprint runners, volleyball players, and untrained subjects. We found that (i) indirect symptoms of exercise-induced muscle damage (prolonged decrease in maximal voluntary contraction, isokinetic concentric torque, and electrically induced (20 Hz) torque) were most evident in untrained subjects, while there were no significant differences in changes of muscle soreness and plasma creatine kinase 48 h after eccentric exercise between athletes and untrained subjects; (ii) low-frequency fatigue was greater in untrained subjects and volleyball players than in sprint runners and long-distance runners; (iii) in all subjects, electrically induced (100 Hz) torque decreased significantly by about 20%, while central activation ratio decreased significantly by about 8% in untrained subjects and sprint runners, and by about 3%-5% in long-distance runners and volleyball players. Thus, trained subjects showed greater resistance to exercise induced muscle damage for most markers, and long-distance runners had no advantage over sprint runners or volleyball players. PMID- 22050127 TI - Contact allergy to methylchoroisothiazolinone/methylisothiazolinone (MCI/MI): findings from a contact dermatitis unit. AB - INTRODUCTION: Several preservatives are currently allowed in cosmetic products in the EU. However, only a few of them are strongly represented on the market: formaldehyde, parabens, formaldehyde releasers and methylchoroisothiazolinone/methylisothiazolinone (MCI/MI). MCI/MI has been widely used during recent years for the preservation of aqueous systems in cosmetics, toiletries and in several industrial applications. OBJECTIVE: To describe the frequency of contact allergy to (MCI/MI) in a contact dermatitis unit. MATERIALS AND METHODS: A retrospective study was conducted including all patients submitted to patch testing, from January 2007 to December 2009. RESULTS: In total, 629 consecutive patients with a clinical diagnosis of contact dermatitis were patch tested over a period of 3 years. The frequency of positive reaction to MCI/MI was 2.4% (15/629). Of the positive patients, 26.5% (4/15) gave a history of atopy. The dermatitis was generalized in 4 patients (26.5%), localized to the head and neck in 3 patients, and involved hands or feet in 9 patients. Other allergen sensitivities were found to occur simultaneously in the majority of cases: two patients (2/15) were allergic to fragrance mix 1 (FM1) and one (1/15) was allergic to fragrance mix 2 (FM2) as well as two (2/15) were allergic to chromium and three (3/15) were allergic to nickel. In 80% of the cases (12/15), the reaction was judged to be of current relevance for products used in personal hygiene. CONCLUSION: The frequency of positive reactions to MCI/MI reported in our study is in the middle range thus far reported in European series in the literature. MCI/MI is a very common biocide for use by the general public at the established allowed concentration, which has been subject of successive measures of regulation considering the compound's current nearly ubiquitous presence in cosmetics. Certain factors appear to increase the risk of sensitization, namely chronic dermatitis and the frequent use of leave-on products containing MCI/MI by these patients. PMID- 22050126 TI - Preparation of stable electroneutral nanoparticles of sodium dodecyl sulfate and branched poly(ethylenimine) in the presence of pluronic F108 copolymer. AB - Mixing of polyelectrolyte solutions with solutions of oppositely charged surfactants usually leads to phase separation in a certain concentration range. However, since the charge-neutralized polyelectrolyte/surfactant nanoparticles might be utilized as versatile nanocarriers of different substances, it would be desirable to prevent their aggregation for some applications. As it was revealed in earlier investigations, the complete suppression of precipitation may be achieved only in mixtures of ionic surfactants and appropriate copolymer polyelectrolytes with nonionic and ionic blocks. In this work, we present a method that could prevent phase separation in mixtures of homopolyelectrolytes and oppositely charged surfactants. Specifically, it is shown that nonaggregating electroneutral nanocomplexes of branched poly(ethylenimine) (PEI) and sodium dodecyl sulfate (SDS) can be prepared in the presence of the amphiphilic triblock copolymer Pluronic F108, provided that an adequate mixing protocol is used for preparation of the PEI/SDS/F108 mixtures. PMID- 22050140 TI - The rare occurrence of three subungual melanomas in one patient. AB - Subungual melanoma commonly presents with solitary longitudinal melanonychia. Herein, we report the case of a patient with subungual melanoma who developed involvement of three digits by three independent primary melanomas. A 98-year-old male patient presented with a two-year history of longitudinal melanonychia on three different fingernails. Histopathologically, all three lesions were proved to be melanoma. To our knowledge, this is the first reported case in which three subungual melanomas developed in one patient. Our case indicates that that not all examples of multiple longitudinal melanonychia represent benign lesions. PMID- 22050133 TI - The effect of branched chain amino acids on psychomotor performance during treadmill exercise of changing intensity simulating a soccer game. AB - The present study was designed to determine changes in the multiple-choice reaction time (MRT) during treadmill running simulating locomotor activity during a soccer game and to examine the effect of branched chain amino acids (BCAA) ingestion on psychomotor performance during the effort. Ten male soccer players were submitted to BCAA and placebo trials at 1-week intervals in a randomized order. BCAA (7 g) or placebo were given 1 h before exercise in a double blind manner. The running test consisted of two 45 min exercise bouts separated by a 15 min passive rest period and the whole test ended with 20-min active recovery. Running-walking speed changed from 0 to 6.4 m.s-1 according to the time-motion analysis of soccer match. During the test, blood samples were taken for lactate, glucose, free fatty acid, and catecholamine determination. Following placebo treatment, MRT shortened from 320 +/- 18 to 271 +/- 11 ms (p < 0.001) during the first exercise bout then it increased during the resting break to 303 +/- 138 ms (p < 0.05). During the second bout, MRT decreased to 280 +/- 13 ms (p < 0.001). During active recovery, further shortening of MRT was noted. During BCAA trial, MRT was shorter than during placebo trial by ~10% (p < 0.05) before and during exercise. No significant differences were found between BCAA and placebo trials in biochemical indices. It is concluded that BCAA supplementation might be recommended in sport activities that change in intensity and require quick responses to external signals (e.g., soccer and other team games). PMID- 22050137 TI - Nurse-administered propofol sedation for gastrointestinal endoscopic procedures: first Nordic results from implementation of a structured training program. AB - INTRODUCTION: Proper training to improve safety of NAPS (nurse-administered propofol sedation) is essential. OBJECTIVE: To communicate our experience with a training program of NAPS. MATERIALS AND METHODS: In 2007, a training program was introduced for endoscopists and endoscopy nurses in collaboration with the Department of Anaesthesiology. During a 2.5-year period, eight nurses were trained. Propofol was given as monotherapy. The training program for nurses consisted of a 6-week course including theoretical and practical training whereas the training program for endoscopists consisted of 2.5 h of theory. Patients were selected based on strict criteria including patients in ASA (American Society of Anesthesiologists) group I-III. RESULTS: 2527 patients undergoing 2.656 gastrointestinal endoscopic procedures were included. The patients were ASA group I, II and III in 34.7%, 56% and 9,3%, respectively. Median dose of propofol was 300 mg. No mortality was noted. 119 of 2527 patients developed short lasting hypoxia (4.7%); 61 (2.4%) needed suction; 22 (0.9%) required bag-mask ventilation and 8 (0.3%) procedures had to be discontinued. In 11 patients (0.4%), anesthetic assistance was called due to short lasting desaturation. 34 patients (1.3%) experienced a change in blood pressure greater than 30%. CONCLUSION: NAPS provided by properly trained nurses according to the present protocol is safe and only associated with a minor risk (short lasting hypoxia 4.7%). National or international structured training programs are at present few or non-existing. The present training program has documented its value and is suggested as the basis for the current development of guidelines. PMID- 22050136 TI - Single-institution experience with solid pseudopapillary neoplasm of the pancreas. AB - OBJECTIVE: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare clinical entity. The objective of this study was to review a single institution's experience with this uncommon tumor, as well as review the literature. MATERIAL AND METHODS: Consecutive patients, who underwent surgery for a pathologically confirmed SPN between 1991 and 2010, were retrospectively reviewed. A PubMed search (January 1980-June 2011) was conducted to identify risk factors for death among SPN patients. RESULTS: The institutional review identified 16 patients with SPN. Thirteen patients were female and three patients were male (median age 34 years). All patients underwent radical resection. Two patients had metastatic disease at the time of operation as evident by the presence of lymph node metastasis and gallbladder metastasis. One developed liver metastasis 4 months postoperatively and subsequently died. The other patient received adjuvant chemotherapy (gemcitabine and capecitabine), and 23 months after the initial operation, no tumor recurrence was detected and the patient is still alive. All other patients remain disease-free. Analysis of 29 fatalities reported in the English literature (including the present case) revealed several atypical features including male gender, old age, tumor size >5 cm, diffuse growth pattern, cellular or nuclear atypia, high mitotic rate, extensive necrosis, extrapancreatic invasion, metastasis and incomplete resection. CONCLUSIONS: SPN is not always indolent. Male patients and those with old age, atypical histopathology (large tumors, diffuse growth, cellular/nuclear atypia, mitotic activity, necrosis, invasion/metastasis) and incomplete resection may have a higher risk of recurrence and death, deserving particular attention. PMID- 22050143 TI - Diagnosis, therapy, and prevention of common infectious diseases in the cat. PMID- 22050142 TI - Diagnosis, therapy, and prevention of common infectious diseases in the dog. PMID- 22050139 TI - Silver distribution and release from an antimicrobial denture base resin containing silver colloidal nanoparticles. AB - PURPOSE: The aim of this study was to evaluate a denture base resin containing silver colloidal nanoparticles through morphological analysis to check the distribution and dispersion of these particles in the polymer and by testing the silver release in deionized water at different time periods. MATERIALS AND METHODS: A Lucitone 550 denture resin was used, and silver nanoparticles were synthesized by reduction of silver nitrate with sodium citrate. The acrylic resin was prepared in accordance with the manufacturers' instructions, and silver nanoparticle suspension was added to the acrylic resin monomer in different concentrations (0.05, 0.5, and 5 vol% silver colloidal). Controls devoid of silver nanoparticles were included. The specimens were stored in deionized water at 37 degrees C for 7, 15, 30, 60, and 120 days, and each solution was analyzed using atomic absorption spectroscopy. RESULTS: Silver was not detected in deionized water regardless of the silver nanoparticles added to the resin and of the storage period. Micrographs showed that with lower concentrations, the distribution of silver nanoparticles was reduced, whereas their dispersion was improved in the polymer. Moreover, after 120 days of storage, nanoparticles were mainly located on the surface of the nanocomposite specimens. CONCLUSIONS: Incorporation of silver nanoparticles in the acrylic resin was evidenced. Moreover, silver was not detected by the detection limit of the atomic absorption spectrophotometer used in this study, even after 120 days of storage in deionized water. Silver nanoparticles are incorporated in the PMMA denture resin to attain an effective antimicrobial material to help control common infections involving oral mucosal tissues in complete denture wearers. PMID- 22050131 TI - Is peak oxygen uptake a determinant of moderate-duration self-paced exercise performance in the heat? AB - This study aimed to identify whether reductions in peak oxygen uptake (VO2(peak)) dictate performance outcomes during 30 min of self-paced exercise in the heat, which is expected to induce minimal hyperthermia. On 4 occasions, 11 male subjects completed peak and self-paced exercise in both hot (HOT, 40.2 +/- 0.3 degrees C) and moderate (MOD; 20.4 +/- 0.7 degrees C) conditions. During peak exercise, submaximal oxygen uptake (VO2) was ~8% higher in HOT, but VO2(peak) (MOD, 4.64 +/- 0.83 L.min-1; HOT, 4.54 +/- 0.77 L.min-1) and peak cardiac output (Q(peak)) were similar. Self-paced exercise performance was reduced by ~21% in HOT. VO2 was similar through 15 min, but lower in HOT thereafter. Relative to MOD, this represented a higher and lower %VO2(peak) during the initial and latter stages. Cardiac output was similar in both trials (MOD, 31.6 +/- 6.6 L.min-1; HOT, 30.1 +/- 6.0 L.min-1), representing a similar percentage of Q(peak) throughout. Rectal temperature was similar in both conditions until 30 min (MOD, 38.5 +/- 0.3 degrees C; HOT, 38.7 +/- 0.3 degrees C), while skin temperature was higher throughout in HOT (mean: MOD, 32.4 +/- 1.1 degrees C; HOT, 37.3 +/- 0.4 degrees C). Perceived exertion rose similarly in both conditions, while thermal discomfort was higher in HOT. These data indicate that when only skin temperature is elevated, reductions in exercise performance during moderate duration self-paced exercise are not associated with changes in VO2(peak). Rather, increases in VO2 at a given submaximal external workload and (or) thermal discomfort appear to play a larger role. PMID- 22050141 TI - Randomised clinical trial: the efficacy of treatment, guided by a shorter duration of response, using peginterferon alfa-2a plus ribavirin for hepatitis C virus other than genotypes 2 or 3. AB - BACKGROUND: The efficacy of individualised antiviral treatment durations for chronic hepatitis C remains unclear. AIM: To evaluate treatment durations based on virological responses at week 4, 8 and 12 of peginterferon alfa-2a plus ribavirin therapy. METHODS: Previously untreated patients with HCV genotypes, other than 2 or 3, initiated therapy with peginterferon alfa-2a 180 MUg/week plus ribavirin 1000-1400 mg/day. HCV-RNA-negative patients at week 4 rapid virological response (RVR) were randomised to 24 or 48 weeks of treatment; those negative at week 8 were randomised to 36 or 48 weeks; and those who were negative or had a >= 2-log drop at week 12 were randomised to 72 or 48 weeks. Sustained virological response (SVR) was defined as undetectable HCV-RNA after 24 weeks of follow-up. RESULTS: The study was terminated prematurely due to lagging enrollment. Of 236 patients who started treatment, 195 were randomised at week 4 (n = 50), 8 (n = 61) or 12 (n = 84). Ninety-five per cent of patients had genotype 1. SVR rates were not significantly different between patients randomised to 24 (84%) or 48 weeks (84%) at week 4, to 36 (73%) or 48 weeks (74%) at week 8, or to 48 (49%) or 72 weeks (40%) at week 12. CONCLUSIONS: In this predominantly genotype 1 cohort, shortening therapy to 24 weeks in patients with a week-4 response and 36 weeks in those with a week-8 response produced SVR rates that were similar to a 48-week regimen. Lengthening treatment to 72 weeks did not improve SVR rates. Genotype 1 patients with RVR can be treated for 24 weeks. PMID- 22050149 TI - Diagnosis, pathogenesis, and treatment of neck lesions in cats. PMID- 22050138 TI - Preclinical antitumor activity of the novel heat shock protein 90 inhibitor CH5164840 against human epidermal growth factor receptor 2 (HER2)-overexpressing cancers. AB - Heat shock protein 90 (Hsp90), a molecular chaperone that plays a significant role in the stability and maturation of client proteins, including oncogenic targets for cell transformation, proliferation, and survival, is an attractive target for cancer therapy. We identified the novel Hsp90 inhibitor, CH5164840, and investigated its induction of oncogenic client protein degradation, antiproliferative activity, and apoptosis against an NCI-N87 gastric cancer cell line and a BT-474 breast cancer cell line. Interestingly, CH5164840 demonstrated tumor selectivity both in vitro and in vivo, binding to tumor Hsp90 (which forms active multiple chaperone complexes) in vitro, and being distributed effectively to tumors in a mouse model, which, taken together, supports the decreased levels of phosphorylated Akt by CH5164840 that we observed in tumor tissues, but not in normal tissues. As well as being well tolerated, the oral administration of CH5164840 exhibited potent antitumor efficacy with regression in NCI-N87 and BT 474 tumor xenograft models. In addition, CH5164840 significantly enhanced antitumor efficacy against gastric and breast cancer models when combined with the human epidermal growth factor receptor 2 (HER2)-targeted agents, trastuzumab and lapatinib. These data demonstrate the potent antitumor efficacy of CH5164840 when administered alone, and its significant combination efficacy when combined with trastuzumab or lapatinib, supporting the clinical development of CH5164840 as an Hsp90 inhibitor for combination therapy with HER2-targeted agents against HER2-overexpressing tumors. PMID- 22050134 TI - Muscle damage slows oxygen uptake kinetics during moderate-intensity exercise performed at high pedal rate. AB - This study aimed to investigate the dependence of oxygen uptake (VO2) kinetics on pedal cadence during moderate-intensity exercise following exercise-induced muscle damage (EIMD). Twenty untrained males were randomly assigned to a 50 revolution per minute (rpm) (age, 23.3 +/- 1.8 years; VO2(max), 38.9 +/- 2.8 mL.kg-1.min-1) or 100 rpm group (age, 24.4 +/- 3.5 years, VO2(max), 42.9 +/- 4.3 mL.kg-1.min-1). Participants completed "step" tests to moderate-intensity exercise from an unloaded baseline on a cycle ergometer before (baseline) and at 24 and 48 h after muscle-damaging exercise (10 sets of 10 eccentric contractions performed on an isokinetic dynamometer with a 2-min rest between each set). Pedal cadence was kept constant throughout each cycling trial (50 or 100 rpm). There were no changes in phase II pulmonary VO2 kinetics following EIMD for the 50 rpm group (baseline = 35 +/- 4 s; 24 h = 35 +/- 7 s; and 48 h = 36 +/- 9 s). However, the phase II VO2 was significantly greater at 24 h (59 +/- 27 s) compared with baseline (39 +/- 6 s) and 48 h (40 +/- 9 s) for the 100 rpm group. It is concluded that the effects of EIMD on phase II VO2 kinetics during moderate intensity cycling exercise is dependent on pedal cadence. The slower VO2 kinetics after muscle damage suggests that type II fibers are involved during transition to moderate-intensity exercise at high pedal cadence. PMID- 22050150 TI - Diffuse neuromuscular disorders. PMID- 22050148 TI - Aspects of obstetric care in the dog. PMID- 22050145 TI - Cat scratch disease. PMID- 22050146 TI - Toxocarosis in dogs and cats. PMID- 22050147 TI - Canine pediatrics. PMID- 22050155 TI - Evaluation of pet foods. PMID- 22050152 TI - Prognostic factors for malignant lymphoma in the dog: An update. PMID- 22050153 TI - Growth and growth hormone in the dog. PMID- 22050151 TI - Seizures and behavioral abnormalities in dogs and cats with neurological dysfunction. PMID- 22050154 TI - Recent advances in dietary management of hepatic diseases. PMID- 22050144 TI - Some aspects of vaccination in companion animal practice. PMID- 22050157 TI - Ultrasonography of the thoracic cavity. PMID- 22050156 TI - Calcium chloride as urinary acidifier in relation to its potential use in the prevention of struvite urolithiasis in the cat. PMID- 22050158 TI - An introduction to ultrasonographic imaging. PMID- 22050159 TI - Basic principles of abdominal radiography. PMID- 22050160 TI - Diseases and management of pet fishes. PMID- 22050161 TI - Differential approach to house-soiling by dogs and cats. PMID- 22050162 TI - Differential approach to aggression by dogs and cats. PMID- 22050163 TI - Pathological anticipatory defence behavior in dogs. PMID- 22050164 TI - Fly snapping syndrome in dogs. PMID- 22050165 TI - Social behavior of wolves and dogs. PMID- 22050166 TI - Commonly encountered feline behavior problems. PMID- 22050167 TI - Dogs have feelings. PMID- 22050168 TI - Disciplinary law. PMID- 22050169 TI - What does vaccination mean to your clients? PMID- 22050170 TI - Marketing in my practice. PMID- 22050171 TI - For or against lens implantation in dogs. PMID- 22050172 TI - Ct and ultrasonographic diagnosis of canine hydrocephalus. PMID- 22050173 TI - Diabetes insipidus in a dog with an alphaMSH-producing pituitary tumor. PMID- 22050174 TI - Mycosis fungoides: A dermatological puzzle. PMID- 22050175 TI - Coccidioidomycosis in a dog. PMID- 22050177 TI - Osteoprotegerin is associated with cardiovascular risk in hypertension and/or diabetes. AB - BACKGROUND: Osteoprotegerin (OPG), a secreted member of the tumour necrosis factor receptor superfamily of cytokines, has been associated with endothelial dysfunction. We studied in type 2 diabetic and/or hypertensive patients the relationship between serum OPG and vascular alterations associated with these pathologies. MATERIALS AND METHODS: We analysed 191 consecutive patients (52 with type 2 diabetes and 139 hypertensive nondiabetic patients) and 54 healthy controls. We assessed the relationship of OPG serum levels measured by ELISA with basal glycaemia, glycosylated haemoglobin, blood pressure, endothelial dysfunction (assessed by pulse wave velocity), retinopathy (by Keith-Wagener classification), left ventricular hypertrophy (by Cornell index), cardiovascular risk and target organs (heart, vascular, kidney) damage. RESULTS: Serum OPG levels were higher in either hypertensive or diabetic patients and in patients with non-dipper and riser circadian blood pressure patterns. We found significant correlations between OPG levels and age, height, glycaemia, systolic, diastolic and pulse blood pressure, pulse wave velocity and left ventricular hypertrophy in both hypertensive and diabetic patients. OPG levels were also higher in hypertensive patients with retinopathy, patients with high probability of 10-year cardiovascular risk, patients with three or more damaged target organs (heart, vessels, kidneys) and patients with previous episodes of ischaemic cardiopathy or hypercholesterolaemia. CONCLUSIONS: Osteoprotegerin is an indicator of diabetes- and hypertension-associated vascular pathologies as endothelial dysfunction and cardiovascular risk. PMID- 22050178 TI - Polarizing animal cells via mRNA localization in oogenesis and early development. AB - The localization of mRNAs in developing animal cells is essential for establishing cellular polarity and setting up the body plan for subsequent development. Cellular and molecular mechanisms by which maternal mRNAs are localized during oogenesis have been extensively studied in Drosophila and Xenopus. In contrast, evidence for mechanisms used in the localization of mRNAs encoded by developmentally important genes has also been accumulating in several other organisms. This offers the opportunity to unravel the fundamental mechanisms of mRNA localization shared among many species, as well as unique mechanisms specifically acquired or retained by animals based on their developmental needs. In addition to maternal mRNAs, the localization of zygotically expressed mRNAs in the cells of cleaving embryos is also important for early development. In this review, mRNA localization dynamics in the oocytes/eggs of Drosophila and Xenopus are first summarized, and evidence for localized mRNAs in the oocytes/eggs and cleaving embryos of other organisms is then presented. PMID- 22050179 TI - Efficacy of risperidone in children with disruptive behavioural disorders. AB - This study aims to review the evidence for the efficacy of risperidone in the treatment of disruptive behavioural disorders (DBDs) in children and adolescents. Established databases were searched using the terms 'Risperidone and efficacy and children' and 'Risperidone and efficacy and adolescents'. Randomised, double blind controlled studies were retained for analysis. Janseen-Cilag was contacted to identify any unpublished studies. Quality of studies was measured using Jadad scores. Seven studies of 657 subjects with a mean age of 9.9 years (SD= 2.0) (range 4-18 years) were identified. Only one study was judged to use the highest quality of methodology according to the Jadad score. Patients with DBD who were treated with risperidone showed clinical improvement compared with placebo. Weight gain, somnolence and gastrointestinal complaints were common. Risperidone was found to be efficacious in reducing symptoms in children and adolescents with DBD. However, studies were mostly of short duration and had deficiencies in the descriptions of blinding and randomisation. Research using rigorous methodology examining the long-term outcomes of efficacy and safety are required to inform clinicians and families of the therapeutic benefits and risks of risperidone in this clinical population. PMID- 22050180 TI - The Chinese Youth Attitudes toward Young Drug Users scale: an initial scale development and refinement. AB - INTRODUCTION AND AIMS: Little is known about adolescents' perspectives of young drug users, especially in the Chinese context. This study aimed to develop a scale to measure Chinese youth attitudes toward young drug users. DESIGN AND METHODS: Initially, a total of 26 non-at-risk and at-risk adolescents (15 male and 11 female) aged 13 to 20 years were interviewed in five separate focus group sessions to explore their general views of young drug users. At-risk youths recruited in this study were adolescents who previously had contact with the juvenile justice system. The responses of these 26 adolescents were documented, and subsequently 25 items were generated out of the respondents' common themes. These 25 items were then surveyed in a group of 137 secondary school-aged adolescents (68 male and 69 female), ranging 13 to 17 years, to examine its underlying factor structure for further scale refinement, with the use of the exploratory factor analysis. RESULTS: A five-factor structure with 12 items was ultimately selected for the Chinese Youth Attitudes toward Young Drug Users (CYAYDU) scale. DISCUSSION AND CONCLUSIONS: This newly developed scale is anticipated to provide utility in the social work settings, especially for youth social workers to assist in providing effective social services to young drug users. Despite the promising strength of the CYAYDU scale, further validation with large sample size is needed. PMID- 22050181 TI - Dynamics of structure formation in a discotic liquid crystal by infrared spectroscopy and related techniques. AB - The dynamics of the herringbone structure formation have been studied in a monobromo hexa-peri-hexabenzocoronene derivative by infrared spectroscopy and complementary techniques. Selective probing of the vibration modes corresponding to the aromatic core and the alkyl chains, allowed investigation of their role in the phase transformation dynamics over an extraordinarily broad time-window (1 10(5) s). Identical kinetics were found suggesting that both the core and the alkyl chains simultaneously drive the system from the undercooled liquid crystalline to the crystalline phase with the herringbone structure. PMID- 22050182 TI - Anti-proliferative effect of rosiglitazone on angiotensin II-induced vascular smooth muscle cell proliferation is mediated by the mTOR pathway. AB - VSMC (vascular smooth muscle cell) proliferation contributes significantly to intimal thickening in atherosclerosis, restenosis and venous bypass graft diseases. Ang II (angiotensin II) has been implicated in VSMC proliferation though the activation of multiple growth-promoting signals. Although TZDs (thiazolidinediones) can inhibit VSMC proliferation and reduce Ang II-induced fibrosis, the mechanism underlying the inhibition of VSMC proliferation and fibrosis needs elucidation. We have used primary cultured rat aortic VSMCs and specific antibodies to investigate the inhibitory mechanism of rosiglitazone on Ang II-induced VSMC proliferation. Rosiglitazone treatment significantly inhibited Ang II-induced rat aortic VSMC proliferation in a dose-dependent manner. Western blot analysis showed that rosiglitazone significantly lowered phosphorylated ERK1/2 (extracellular-signal-regulated kinase 1/2), Akt (also known as protein kinase B), mTOR (mammalian target of rapamycin), p70S6K (70 kDa S6 kinase) and 4EBP1 (eukaryotic initiation factor 4E-binding protein) levels in Ang II-treated VSMCs. In addition, PPAR-gamma (peroxisome-proliferator-activated receptor gamma) mRNA increased significantly and CTGF (connective tissue growth factor), Fn (fibronectin) and Col III (collagen III) levels decreased significantly. The results demonstrate that the rosiglitazone directly inhibits the pro-atherosclerotic effect of Ang II on rat aortic VSMCs. It also attenuates Ang II-induced ECM (extracellular matrix) molecules and CTGF production in rat aortic VSMCs, reducing fibrosis. Importantly, PPAR-gamma activation mediates these effects, in part, through the mTOR-p70S6K and -4EBP1 system. PMID- 22050183 TI - Highly sensitive elemental analysis for Cd and Pb by liquid electrode plasma atomic emission spectrometry with quartz glass chip and sample flow. AB - This paper describes the development of a highly sensitive liquid-electrode plasma atomic emission spectrometry (LEP-AES) by combination of quartz glass chip and sample flow system. LEP-AES is an ultracompact elemental analysis method, in which the electroconductive sample solution is put into a microfluidic channel whose center is made narrower (~100 MUm in width). When high voltage pulses (1500 V) are applied at both ends of the channel, the sample evaporates locally at the narrow part and generates plasma. By the emission from the plasma, elemental concentration is analyzed. In this paper, the limits of detection (LODs) were investigated in various conditions of accumulation time, material of the chip, and the sample flow. It was found that the long accumulation using the quartz chip with sample flow was effective to improve LOD. Authors suggested that this was because bubbles remaining after each plasma pulse were removed from the narrow channel by sample flow, resulting in highly reproducible plasma generation, to enable a high accumulation effect. Finally, LODs were calculated from a calibration curve, to be 0.52 MUg/L for Cd and 19.0 MUg/L for Pb at optimized condition. Sub-ppb level LOD was achieved for Cd. PMID- 22050184 TI - Pharmacologic strategies for improvement of islet survival: targeting the enterohormonal axis. PMID- 22050185 TI - The right to refuse. PMID- 22050186 TI - The mucosa beyond the polyps in juvenile polyposis. AB - Little is known of early histologic changes in the mucosa of the colon aside from the polyps in Juvenile Polyposis. Provided with a surgical specimen of a total colectomy of a 6-year-old boy with this condition, this report describes those changes. The mucosa depicted a peculiar serrated profile of the uppermost part of the crypts due to elongation of them, dilated openings, and scant stroma. Also present were frequent aberrant crypts. Early juvenile polyps presented associated with lympho-glandular sites as distorted and microcystically dilated crypts containing granular and filamentous mucoid material. The findings possibly represent the abnormal cytologic potential of this genetic condition. PMID- 22050187 TI - Electronic structures and spectroscopy of the electron transfer series [Fe(NO)L2]z (z = 1+, 0, 1-, 2-, 3-; L = dithiolene). AB - The electronic structures and spectroscopic parameters for the electron transfer series of [Fe(NO)(L)(2)](z) (z = 1+, 0, 1-, 2-, 3-; L = S(2)C(2)R(2); R = p-tolyl (1) and CN (2)) were calculated and compared to experiment. Some compounds in the series were isolated and characterized by spectroscopy. The calculations support the notion that all the monocation (S(t) = 0), neutral (S(t) = 1/2), and monoanion (S(t) = 0) complexes contain NO(+) (S(NO) = 0), in which the redox active fragment is either the bis-dithiolene (2 L) or the central iron. The calculated electronic structures give insight into how p-tolyl and CN substituents and the redox states of the 2 L ligand impact the spin density on the iron in the monocation and neutral species. The electronic structure of [1](0) has some [Fe(I)(NO(+))(L(2)(2-))](0) character in resonance with [Fe(II)(NO(+))(L(2)(2-))](0) whereas [2](0) has a smaller amount of a [Fe(I)(NO(+))(L(2)(2-))](0) description in its ground state wavefunction. Similarly, the electronic structure of [1](1+) also has some [Fe(I)(NO(+))(L(2)(1 ))](1+) character in resonance with [Fe(II)(NO(+))(L(2)(2-))](1+) whereas [2](1+) is best described as [Fe(II)(NO(+))(L(*))(2)](1+). For the monoanion, the bis dithiolene fragment is fully reduced and both [1](-) and [2](-) are best formulated as [Fe(II)(NO(+))(L(2)(4-))](-). The reduction of the monoanion to give dianions [1](2-) and [2](2-) results in {FeNO}(7) species. The calculated (57)Fe isomer shift and hyperfine couplings are in line with the experiment and support a description of the form [Fe(III)(NO(-))(L(2)(4-))](2-), in which Fe(III) S(Fe) = (3)/(2) is antiferromagnetically coupled to NO(-) (S(NO) = 1). Finally, the calculated redox potential and nu(NO) frequency for the {FeNO}(8) trianionic species [2](3-) is in agreement with experiment and consistent with a triplet ground state [Fe(II)(NO(-))(L(2)(4-))](3-), in which Fe(II) (S(Fe) = 2) is involved in antiferromagnetic coupling with NO(-) (S(NO) = 1). PMID- 22050188 TI - Correlating interface heterostructure, charge recombination, and device efficiency of poly(3-hexyl thiophene)/TiO2 nanorod solar cell. AB - The charge recombination rate in poly(3-hexyl thiophene)/TiO(2) nanorod solar cells is demonstrated to correlate to the morphology of the bulk heterojunction (BHJ) and the interfacial properties between poly(3-hexyl thiophene) (P3HT) and TiO(2). The recombination resistance is obtained in P3HT/TiO(2) nanorod devices by impedance spectroscopy. Surface morphology and phase separation of the bulk heterojunction are characterized by atomic force microscopy (AFM). The surface charge of bulk heterojunction is investigated by Kelvin probe force microscopy (KPFM). Lower charge recombination rate and lifetime have been observed for the charge carriers in appropriate heterostructures of hybrid P3HT/TiO(2) nanorod processed via high boiling point solvent and made of high molecular weight P3HT. Additionally, through surface modification on TiO(2) nan,orod, decreased recombination rate and longer charge carrier lifetime are obtained owing to creation of a barrier between the donor phases (P3HT) and the acceptor phases (TiO(2)). The effect of the film morphology of hybrid and interfacial properties on charge carrier recombination finally leads to different outcome of photovoltaic I-V characteristics. The BHJ fabricated from dye-modified TiO(2) blended with P3HT exhibits 2.6 times increase in power conversion efficiency due to the decrease of recombination rate by almost 2 orders of magnitude as compared with the BHJ made with unmodified TiO(2). In addition, the interface heterostructure, charge lifetime, and device efficiency of P3HT/TiO(2) nanorod solar cells are correlated. PMID- 22050189 TI - Self-reported dry mouth in Swedish population samples aged 50, 65 and 75 years. AB - BACKGROUND: Reduced salivary flow may have a negative impact on general well being, quality of life and oral health. OBJECTIVES: To examine xerostomia in 50-, 65- and 75-year-olds, background factors and effect on Oral Impacts on Daily Performances (OIDP). METHODS: In 1992, a questionnaire was sent to all 50-year old persons (n = 8888) in two Swedish counties. In 2007, the same questionnaire was sent to all 65-year-olds (n = 8313) in the two counties and to all 75-year olds (n = 5195). Response rate was for the 50, 65 and 75 year olds 71.4, 73.1 and 71.9%, respectively. RESULTS: Xerostomia was higher in women than in men in all age groups. There was higher prevalence of xerostomia with increasing age in both sexes and it was more frequent at night than during daytime. 'Often mouth dryness' was 2.6-3.4 times more prevalent in those who reported an impact from OIDP. The highest odd ratios were for daytime xerostomia and for the variables burning mouth (17.1), not feeling healthy (4.5), daily smoking (4.4), and medication (4.1). CONCLUSIONS: The dramatic increase of xerostomia between age 50 and 75, especially amongst women, needs to be considered in the management of this age group. PMID- 22050190 TI - Percutaneous balloon atrioseptostomy for left heart discharge in extracorporeal life support patients with persistent pulmonary edema. AB - AIMS: In severe myocardial dysfunction, extracorporeal life support (ECLS) can preserve organ perfusion. Occasionally, the high resulting afterload can lead to refractory pulmonary edema. We report our experience with percutaneous balloon atrioseptostomy used in this circumstance to discharge the left heart and prevent worsening pulmonary congestion. METHODS AND RESULTS: Between October 2002 and December 2009, 5 patients, with a mean age of 39 years, who were under peripheral ECLS underwent percutaneous balloon atrioseptostomy for refractory worsening pulmonary edema as determined by clinical, radiological, and echocardiographic criteria. Myocardial dysfunction was related to drug poisoning in 2 cases and to myocarditis in the 3 others. Atrioseptostomy successfully improved pulmonary edema and echocardiographic indices of left ventricular function in all cases. Four patients were eventually discharged. The fifth patient died in hospital due to multiorgan failure. CONCLUSIONS: In our experience, percutaneous balloon atrioseptostomy appeared to be a rapid, effective, and minimally invasive technique for offloading the left heart of patients with a reversible cardiac dysfunction under ECLS and suffering from refractory pulmonary edema. PMID- 22050191 TI - Genistein binding mode to doubly nicked dumbbell DNA. Dynamic and diffusion ordered NMR study. AB - New genistein derivatives were synthesized, which are fairly well soluble in water, with respect to parent genistein, and thus facilitate study of the interaction with dumbbell DNA dodecamer, mimicking the biological target for topoisomerase II inhibitors. A pulsed field gradient spin echo NMR experiment was used to check the binding and to estimate the association constants and its pH dependence of genistein with dumbbell DNA. Experimental restraints based on nuclear Overhauser spectroscopy spectra were used to calculate the NMR structure in solution in case of 6,8-disubstituted genistein with dimethylaminomethyl groups and were used in molecular modeling calculations. The structure is dynamic, and 10 molecular dynamics runs yield a family of conformations that essentially differ in a depth of inclusion of genistein into a nick. The paper experimentally shows evidence for binding, intercalation in the nick is proposed as a mode of genistein binding, and a model of the event is provided. PMID- 22050192 TI - A review of primary writing tremor. AB - A task-specific tremor (TST) is a rare form of movement disorder that appears while performing or attempting to perform a particular task. Primary writing tremor (PWT) is the most common form of TST which only occurs during the act of writing and hinders it. (Bain PG, Findley LJ, Britton TC, Rothwell JC, Gresty MA, Thompson PD, Marsden CD. MRC Human Movement, and Balance Unit, Institute of Neurology, London, UK. Primary writing tremor. Brain. 1995;118(6):1461-72.) Primary writing tremor type B is present not only during the act of writing but also when the hand assumes a writing posture. (Bain PG, Findley LJ, Britton TC, Rothwell JC, Gresty MA, Thompson PD, Marsden CD. MRC Human Movement and Balance Unit, Institute of Neurology, London, UK. Primary writing tremor. Brain. 1995;118(6):1461-72.) We first of all describe a remarkable case study of a 50 year old, right-handed male who started experiencing a primary writing tremor in his right hand about a year ago. This case was found to be of particular interest because the patient had it relatively difficult when attempting to write numbers as opposed to writing letters. This review further discusses the clinical manifestations of PWT. In addition, three main hypotheses have been proposed for the causation of PWT, although the exact pathophysiology of PWT still remains unknown. It has been suggested that PWT is a separate entity, a variant of essential tremor and not a separate entity, or a type of dystonia. The various treatment options for PWT are discussed including botulinum toxin and oral pharmacotherapy. PMID- 22050193 TI - A carbohydrate-conjugated deep cavitand permits observation of caviplexes in human serum. AB - A deep cavitand was covalently modified with carbohydrates to provide solubility in biologically relevant environments and to investigate its receptor function. Specifically, a tetrakis(beta-D-glucosyl) cavitand (1) that was soluble in neutral water or acid/base-buffered solutions was synthesized, and it formed complexes with hydrophobic small molecules. Extraction of the cavitand into aqueous sodium dodecyl sulfate micelles as simple membrane mimetics increased the scope of guests bound by 1 beyond that observed in only aqueous media. Complex formation was also detected in human serum. The findings show the functional compatibility of the receptor in both micelle-bound and serum-soluble forms. PMID- 22050194 TI - Interleukin-18 system plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions. AB - BACKGROUND: Keloid scarring is a dermal fibroproliferative disorder characterized by increased fibroblast proliferation and excessive production of collagen and extracellular matrix (ECM) components. To date, the role of cytokines in keloid pathogenesis has not been completely unravelled. Interleukin (IL)-18 is a pro inflammatory cytokine that plays important roles in wound healing, fibrogenesis and carcinogenesis. OBJECTIVES: Our aim was to study the role of the IL-18 system in keloid pathogenesis. MATERIALS AND METHODS: Expression and localization of IL 18 and its receptor (IL-18R) were investigated in normal skin and keloid tissues using Western blot and immunohistochemistry. We further studied the expression of the IL-18 system in normal and keloid-derived cell lines in a coculture model. RESULTS: Results from Western blot and immunohistochemistry revealed that IL-18, IL-18Ralpha and IL-18Rbeta expression was elevated in keloid tissue compared with normal skin tissue. Studies on the expression of IL-18 and its antagonist, IL-18 binding protein (IL-18BP), using a coculture model demonstrated severe IL-18/IL 18BP imbalance in keloid keratinocyte/keloid fibroblast (KK/KF) cocultures with significant elevation of bioactive IL-18 whereas IL-18BP levels remained the same. This overproduction of bioactive IL-18 in keloid cocultures could be due to increased caspase-1 and decreased caspase-3 expression in keloid tissue, as well as decreased soluble IL-10 levels observed in keloid cocultures. The important inductive effects of IL-18 on KFs were further underscored by the observation that exposure of KF to IL-18 resulted in increased collagen and ECM component synthesis, and increased secretion of profibrotic cytokines such as IL-6 and IL 8. Finally, the addition of phosphatidylinositol 3-kinase (PI3K), mitogen activation protein kinase (MAPK), specificity protein 1 (Sp1) and mammalian target of rapamycin (mTOR) inhibitors inhibited IL-18 secretion in keloid cocultures. CONCLUSIONS: The present study has proven that the IL-18 system plays an important role in keloid pathogenesis via epithelial-mesenchymal interactions. It also suggests a therapeutic potential of PI3K, MAPK, Sp1 and mTOR inhibitors in the treatment of keloid scarring. PMID- 22050195 TI - Hydroxychloroquine retinopathy combined with retinal pigment epithelium detachment. AB - PURPOSE: To describe a case of hydroxychloroquine retinopathy combined with retinal pigment epithelium (RPE) detachment and evaluate possible causes of pigment epithelium detachment. METHODS: Single case report and literature review. RESULTS: A 44-year-old lady presented with "decreasing visual acuity and field since a few months ago". She was diagnosed with systemic lupus erythematosus and had been on hydroxychloroquine 400 mg orally twice daily for 10 years. Fluorescein angiography and fundus autofluorescence revealed the decrease in RPE amount or function in the right eye. Spectral domain optical coherence tomography revealed preservation of central foveal outer retinal structure surrounded by perifoveal outer retinal thinning in the right eye. Adjacent to fovea, between fovea and disc, large sized RPE detachment was seen. CONCLUSION: We herein report the first case of hydroxychloroquine retinopathy combined with RPE detachment. RPE dysfunction caused by long-term use of hydroxychloroquine can be manifested as pigment epithelium detachment. PMID- 22050197 TI - Theoretical analysis of [5.7](n)cyclacenes: closed-shell cyclacene isomers. AB - The [5.7](n)cyclacenes represent a novel class of all sp(2)-hybridized carbon structures. In contrast to the isomeric [n]cyclacenes, [5.7](n)cyclacenes are predicted at the B3LYP/6-31G* level of theory to have stable, closed-shell singlet ground state configurations. Predicted geometries, electronic structures, band gaps, nucleus-independent chemical shift (NICS) values, and strain energies for this new family of cyclic conjugated molecules are presented. PMID- 22050198 TI - European veterinary dissertations. PMID- 22050199 TI - Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis. AB - BACKGROUND: Thiazolidinediones (TZDs) have been used in the treatment of non alcoholic steatohepatitis (NASH). However, the magnitude of treatment response associated with TZDs in improving liver histology in NASH has not been quantified systematically. AIM: To conduct a meta-analysis of randomised, placebo-controlled clinical trials (RPCTs) using pioglitazone and rosiglitazone in the treatment of NASH. METHODS: Pubmed/MEDLINE and Cochrane Central Register of Controlled Trials 2010 were searched until September 2010 and four RPCTs were identified. Peto odds ratios (ORs) and their respective 95% confidence intervals (CIs) were used to assess the efficacy of TZDs in improving liver histological parameters. RESULTS: Four good quality RPCTs derived from three continents were included. The meta analysis showed that TZDs (n = 169) were significantly better than placebo (n = 165) in improving ballooning degeneration, lobular inflammation and steatosis with combined ORs of 2.11 (95% CI, 1.33-3.36), 2.58 (95% CI, 1.68-3.97) and 3.39 (95% CI, 2.19-5.25) respectively. The improvement in combined necroinflammation with TZD (n = 58) vs. placebo (n = 52) was also statistically significant (combined OR 6.52[95% CI, 3.03-14.06]), but improvement in fibrosis was not. When pioglitazone (n = 137) was analysed alone, the improvement in fibrosis with pioglitazone (n = 137) vs. placebo (n = 134) (combined OR 1.68 [95% CI, 1.02 2.77]) was statistically significant. The total body fat slightly decreased in the control, while it markedly and highly significantly increased with TZD treatment. CONCLUSIONS: Thiazolidinediones significantly improve ballooning degeneration, lobular inflammation, steatosis and combined necroinflammation in patients with NASH. Pioglitazone may improve fibrosis. Larger randomised, placebo controlled clinical trials are needed to examine the efficacy of thiazolidinediones in improving NASH fibrosis. PMID- 22050200 TI - Exercise-induced respiratory symptoms not due to asthma. AB - This manuscript describes two interesting patients who had exercise-induced symptoms that unmasked an alternative underlying diagnosis. The first is an 8 year-old boy who was treated for asthma all his life but really had exercise induced stridor (labelled as wheeze) causing significant exercise limitation, which was due to a double aortic arch with the right arch compressing the trachea. The second case describes the diagnosis of vocal cord dysfunction in a 13-year-old anxious high achiever. He also initially had exercise-induced symptoms treated as exercise-induced wheeze but again had a stridor due to vocal cord dysfunction. Both these cases demonstrate the importance of detailed history including during exercise, which can unmask alternative diagnosis. Another important message is that if there is no response to bronchodilator treatment with absence of typical signs and symptoms of asthma, alternative diagnosis should be considered. PMID- 22050201 TI - Characterization of induced Staphylococcus aureus bacteriophage SAP-26 and its anti-biofilm activity with rifampicin. AB - Lytic bacteriophages (phages) have been investigated as treatments for bacterial infectious diseases. An induced phage, SAP-26, was isolated from a clinical isolate of Staphylococcus aureus. It belongs to the family Siphoviridae and its genome consists of double-stranded 41,207 bp DNA coding for 63 open reading frames. The phage SAP-26 showed a wide spectrum of lytic activity against both methicillin-resistant S. aureus and methicillin-susceptible S.aureus. Furthermore, combined treatment with a phage and antimicrobial agents showed a strong biofilm removal effect which induced structural changes in the biofilm matrix and a substantial decrease in the number of bacteria. Such a broad host range in S. aureus and biofilm removal activity of the phage SAP-26 suggests the possibility of its use as a therapeutic phage in combination with appropriate antimicrobial agent(s). Among the three antimicrobial agents combined with phage, the combination of rifampicin showed the best biofilm removal effect. To the authors' knowledge, this study showed for the first time that S. aureus biofilm could be efficiently eradicated with the mixture of phage and an antimicrobial agent, especially rifampicin. PMID- 22050202 TI - Metastatic chondrosarcoma - current aspects of a rare event in dermatopathology. PMID- 22050203 TI - Metal-controlled assembly of uranyl diphosphonates toward the design of functional uranyl nanotubules. AB - Two uranyl nanotubules with elliptical cross sections were synthesized in high yield from complex and large oxoanions using hydrothermal reactions of uranyl salts with 1,4-benzenebisphosphonic acid or 4,4'-biphenylenbisphosphonic acid and Cs(+) or Rb(+) cations in the presence of hydrofluoric acid. Disordered Cs(+)/Rb(+) cations and solvent molecules are present within and/or between the nanotubules. Ion-exchange experiments with A(2){(UO(2))(2)F(PO(3)HC(6)H(4)C(6)H(4)PO(3)H)(PO(3)HC(6)H(4)C(6)H(4)PO(3))}.2H(2 O (A = Cs(+), Rb(+)), revealed that A(+) cations can be exchanged for Ag(+) ions. The uranyl phenyldiphosphonate nanotubules, Cs(3.62)H(0.38)[(UO(2))(4){C(6)H(4)(PO(2)OH)(2)}(3){C(6)H(4)(PO(3))(2)}F(2)].nH(2 O, show high stability and exceptional ion-exchange properties toward monovalent cations, as demonstrated by ion-exchange studies with selected cations, Na(+), K(+), Tl(+), and Ag(+). Studies on ion-exchanged single crystal using scanning electron microscopy and energy dispersive X-ray spectroscopy (SEM/EDS) provide evidence for chemical zonation in Cs(3.62)H(0.38)[(UO(2))(4){C(6)H(4)(PO(2)OH)(2)}(3){C(6)H(4)(PO(3))(2)}F(2)].nH(2 O, as might be expected for exchange through a diffusion mechanism. PMID- 22050204 TI - Treatment of primary autoimmune thrombocytopenia (AITP) [1]. PMID- 22050205 TI - Marginal and internal discrepancies related to margin design of ceramic crowns fabricated by a CAD/CAM system. AB - PURPOSE: The aim of this study was to evaluate the marginal discrepancy (MD) and internal discrepancy (ID) of ceramic crowns manufactured by a CAD/CAM system, having different finish lines. The hypotheses tested were that the finish line type would not influence the MD or ID of the crowns, and ID would not change in different regions. MATERIALS AND METHODS: Three aluminum master dies (height: 5.5 mm, O: 7.5 mm, conicity: 6 degrees ) with different finish lines (TC: tilted chamfer; LC: large chamfer; RS: rounded shoulder) were manufactured. Ten impressions were made from each master die using a modified parallelometer. Impressions were poured in type IV dental stone, and 30 ceramic crowns (IPS Empress CAD, Ivoclar) were subsequently milled. The crowns were fixed on their respective metallic die using a metallic fixation device. The distance between the external edges of the crown to the edge of the cervical preparation was performed at 50 points on the respective metallic die (MD analysis). With the replica technique, the ID values of each crown were further evaluated at 12 points equidistant to each other in three regions: radius (R), axial (A), and occlusal (Occl). The measurements were performed using an optical microscope (250*). The data (MUm) were analyzed using ANOVA and Tukey's test (5%). RESULTS: The RS group (28.24 +/- 11.42 MUm) showed significantly lower MD values (p= 0.001) than those of TC (99.92 +/- 18.32 MUm) and LC (64.71 +/- 25.64 MUm) groups, both of which also differed statistically from one another. The ID results demonstrated significantly lower values in the LC group (183.01 +/- 62.82 MUm) (p= 0.0014) than those of TC (216.26 +/- 83.23 MUm) and RS (219.12 +/- 87.24 MUm) groups. ID results of TC and RS were not significantly different. Additionally, the ID results showed significant differences among the regions (p= 0.0001). The null hypotheses were rejected. CONCLUSION: The RS finish line produced MD values significantly lower than tilted and large chamfer, but large chamfer presented the lowest internal discrepancy values. Independent of the finish line type, internal discrepancy was the lowest in the axial region followed by radius and occlusal regions. PMID- 22050206 TI - Does meal ingestion enhance sensitivity of visceroperception assessment in irritable bowel syndrome? AB - BACKGROUND: Visceral hypersensitivity is frequently observed in irritable bowel syndrome (IBS). Previous studies have shown that administration of a meal can aggravate symptoms or increase visceroperception in IBS patients. We investigated whether meal ingestion could increase the sensitivity of the barostat procedure for the detection of visceral hypersensitivity in IBS patients. METHODS: Seventy one IBS patients and 30 healthy controls (HC) were included in the study. All subjects underwent a barostat procedure under fasted and postprandial conditions to measure visceroperception. Urge, discomfort, and pain were scored on a visual analog scale. Furthermore, percentages of hypersensitive IBS patients and HC were calculated and dynamic rectal compliance was assessed. KEY RESULTS: In IBS patients, urge, discomfort, and pain scores were significantly increased postprandially vs the fasted state. The HC showed increased scores for urge and pain only. Rectal dynamic compliance remained unaltered in both groups. Postprandial hypersensitivity percentages did not significantly differ vs the fasted state in IBS patients, nor in HC. CONCLUSIONS & INFERENCES: Postprandial barostat measurement enhances visceroperception in IBS but has no added value to detect visceral hypersensitivity in individual IBS patients. PMID- 22050207 TI - Validation of FDG-PET/MRI coregistration in nonlesional refractory childhood epilepsy. AB - PURPOSE: To validate the use of 18F-fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging (FDG-PET/MRI) coregistration for epileptogenic zone detection in children with MRI nonlesional refractory epilepsy and to assess its ability to guide a second interpretation of the MRI studies. METHODS: Thirty-one children with refractory epilepsy whose MRI results were nonlesional were included prospectively. All patients underwent presurgical evaluation following the standard protocol of our epilepsy unit, which included FDG-PET and FDG-PET/MRI coregistration. Cerebral areas of decreased uptake in PET and PET/MRI fusion images were compared visually and then contrasted with presumed epileptogenic zone localization, which had been obtained from other clinical data. A second interpretation of MRI studies was carried out, focusing on the exact anatomic region in which hypometabolism was located in FDG-PET/MRI fusion images. KEY FINDINGS: Both FDG-PET and FDG-PET/MRI detected hypometabolism in 67.8% of patients, with good concordance on a subject basis and on the cerebral region involved (kappa statistic = 0.83 and 0.79, respectively). Hypometabolism detected by single PET, as well as by PET/MRI fusion images, was located in the same hemisphere, as indicated by electroclinical data in 58% of patients, and at the same place in 39% of cases. Of the patients who showed hypometabolism on PET/MRI, 43% also experienced changes in the guided second MRI interpretation, from nonlesional to subtle-lesional. SIGNIFICANCE: PET/MRI coregistration is an imaging variant that is at least as accurate as PET alone in detecting epileptogenic zone in pediatric nonlesional patients, and can guide a second look at MRI studies previously reported as nonlesional, turning a meaningful percentage into subtle-lesional. PMID- 22050208 TI - Spatial and temporal infiltration dynamics during managed aquifer recharge. AB - Natural groundwater recharge is inherently difficult to quantify and predict, largely because it comprises a series of processes that are spatially distributed and temporally variable. Infiltration ponds used for managed aquifer recharge (MAR) provide an opportunity to quantify recharge processes across multiple scales under semi-controlled conditions. We instrumented a 3-ha MAR infiltration pond to measure and compare infiltration patterns determined using whole-pond and point-specific methods. Whole-pond infiltration was determined by closing a transient water budget (accounting for inputs, outputs, and changes in storage), whereas point-specific infiltration rates were determined using heat as a tracer and time series analysis at eight locations in the base of the pond. Whole-pond infiltration, normalized for wetted area, rose rapidly to more than 1.0 m/d at the start of MAR operations (increasing as pond stage rose), was sustained at high rates for the next 40 d, and then decreased to less than 0.1 m/d by the end of the recharge season. Point-specific infiltration rates indicated high spatial and temporal variability, with the mean of measured values generally being lower than rates indicated by whole-pond calculations. Colocated measurements of head gradients within saturated soils below the pond were combined with infiltration rates to calculate soil hydraulic conductivity. Observations indicate a brief period of increasing saturated hydraulic conductivity, followed by a decrease of one to two orders of magnitude during the next 50 to 75 d. Locations indicating the most rapid infiltration shifted laterally during MAR operation, and we suggest that infiltration may function as a "variable source area" processes, conceptually similar to catchment runoff. PMID- 22050209 TI - Formation of N-N cross-links in DNA by reaction of radiation-produced DNA base pair diradicals: a DFT study. AB - This study employs DFT (density functional theory) to investigate the formation of hydrazine-like (N-N) cross-linked structures between DNA base pair diradicals that are likely to result from the interaction of high linear energy transfer (LET) radiation, such as ion-beam radiation, with DNA. In our calculations, we generated the guanine (G), cytosine (C), adenine (A), and thymine (T) radicals by removing one hydrogen atom from an N-H bond involved in the normal base pairing. The radical species formed are those that naturally result from one-electron oxidation of the bases followed by deprotonation. N-N cross-links between G and C or A and T diradicals were studied using the BHandHLYP, B3LYP, M06, and M06-2X density functionals and 6-31G* basis set. From a comparison to several test cases performed with the G3B3 method, which gives thermodynamically reliable values, we found that calculations employing the BHandHLYP/6-31G* method predict the best estimates of bonding energies for hydrazine-like structures. Our study shows that the N-N cross-link formed between guanine radical and a neutral cytosine is endothermic in nature but can form metastable structures. However, the reactions between two DNA base radicals (diradical) to form several N-N cross-linked structures are found to be highly exothermic in nature. The N-N cross-links formed between various G-C, G-G, and C-C diradicals have binding energies in the range of ca. -54 to -68, -41 to -47, and -67 to -75 kcal/mol, respectively, whereas A-T, A-A, and T-T have binding energies of -80, -60, and -98 kcal/mol, respectively. In all purine-pyrimidine N-N cross-linked structures, the highest occupied molecular orbital (HOMO) is found to be localized on the purine moiety and the lowest unoccupied molecular orbital (LUMO) is on the pyrimidine moiety. PMID- 22050210 TI - Two novel alleles, HLA-B*40:125 and B*40:129, in the Brazilian population. AB - The new alleles, HLA-B*40:125 and HLA-B*40:129, present a mismatch at codon 103.1 (G -> C) and three mismatches at codons 9.1 (C -> T), 11.1 (T -> G) and 12.1 (G > A). PMID- 22050211 TI - Three hours of training improve psychiatric staff's self-perceived knowledge and attitudes toward problem-drinking patients. AB - INTRODUCTION AND AIMS: Staff attitudes are an important factor in the successful implementation of systematic alcohol strategies and policies. The forms and extent of training needed to improve therapeutic attitude among psychiatric staff to problem drinking are unclear. The aim of the investigation was to study the knowledge and attitudes of psychiatric staff toward problem-drinking patients. A further aim was to investigate whether a short 3 h training is sufficient to improve knowledge and therapeutic attitude toward problem drinking. DESIGN AND METHODS: A tailored training model for psychiatric staff (non-physicians) was carried out at a medium size university clinic. Participants were medical (nurses and psychiatric aides) and non-medical staff (psychologists and social workers). The training consisted of a 2 h workshop and a 1 h follow-up session. Knowledge and attitudes were measured at baseline and follow up by a questionnaire including vignettes assessment and the Short Alcohol and Alcohol Problems Perception Questionnaire. RESULTS: In total, 115 persons completed the questionnaire (follow-up rate 83.5%). The distribution was even (50% for the medical and 50% for the non-medical staff). After training, the non-medical staff estimated vignette case severity higher than before. Both staff groups estimated their capacity to help a patient with complex problems higher after training. Role adequacy was higher in both subgroups after training. Medical staff scored work satisfaction higher after the training. DISCUSSION AND CONCLUSIONS: Three hours of tailored training for psychiatric staff improve their knowledge and therapeutic attitude to problem-drinking patients. PMID- 22050212 TI - Synthesis and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-D-aspartate receptors. AB - As an extension of our studies, novel indole derivatives were rationally designed and synthesized as ligands targeted to GluN2B/NMDA receptors. The 2-(4 benzylpiperidin-1-yl)-1-(6-hydroxy-1H-indol-3-yl)ethanone (4i) and 1-(4 benzylpiperidin-1-yl)-2-(6-hydroxy-1H-indol-3-yl)ethane-1,2-dione (6i) showed high binding affinity in [3H]ifenprodil displacement assay. By computational studies, we suggested the hypothetical interactions playing a significant role during the binding process. However, in functional and in vivo studies the most potent compound 4i did not show any activity whereas it displayed relevant affinity toward the sigma2 receptor. PMID- 22050213 TI - Comment on "Chromium contamination accident in China: viewing environment policy of China". PMID- 22050215 TI - Impact of pinning of the triple contact line on electrowetting performance. AB - Pinning of the triple contact line adversely affects electrowetting on dielectric. Electrowetting response of substrates with contact angle hysteresis ranging from 1 degrees to 30 degrees has been characterized, and the results are interpreted within the framework of electromechanics corrected for pinning. The relationship between contact angle hysteresis, threshold potential for liquid actuation, and electrowetting hysteresis is quantified. Our results demonstrate that a modified electrowetting equation, based on balance of forces (including the pinning forces) acting on the triple contact line and on the drop, describes the electrowetting response of substrates with significant contact angle hysteresis. Finally, the surface properties of PDMS Sylgard 184 were found to be influenced by the electric field. PMID- 22050214 TI - A preliminary assessment of the periodontal status of elderly pensioners in Benin City, Nigeria. AB - AIM: This study was to assess the periodontal status of pensioners in Benin City and obtain baseline data. MATERIALS AND METHODS: The cross-sectional descriptive study involved 250 subjects selected by systematic random sampling from three clusters of general, university and teaching hospital pensioners examined using the Community Periodontal Index index in four locations within Benin City. RESULTS: The percentages of the dentate subjects with healthy gingiva, bleeding on probing, calculus, shallow pockets and deep pockets were 2.4, 5.2, 46.8, 38.8 and 6.8%, respectively. Only 2% needed no periodontal treatment; those requiring oral hygiene instructions, scaling and polishing and complex treatment were 52, 39 and 7%, respectively. There were no significant differences in the periodontal status of the pensioners by gender, age or tooth brushing habits. CONCLUSION: The presence of calculus accounted for the most prevalent periodontal condition among the elderly pensioners followed by shallow periodontal pocketing apparently owing to poor dental attendance or lack of access to care. A comprehensive pensioner's oral health programme is recommended. PMID- 22050216 TI - Lack of health insurance in living kidney donors. AB - Living donors are recommended to receive lifelong routine health maintenance after donation. There has been little examination of health insurance status among living donors, despite the fact that lack of health insurance is likely to impede donors' ability to obtain long-term healthcare post-donation. We performed a retrospective chart review for all living kidney donors at our institution between 2004 and 2008 to determine insurance status, demographic, socioeconomic, and basic health characteristics. Twenty-three percent of donors were uninsured at the time of donation. Odds of being uninsured were significantly lower in donors who were older than 40 yr of age or who had at least a college education, and significantly higher in donors who were non-white, non-English-speaking, or non-US citizens. Odds of being uninsured did not differ according to whether donors were obese, hypertensive, or smokers. On multivariate analysis, only non white race, non-US citizenship, and education level less than a college degree were associated with lack of insurance. Lack of health insurance is more prevalent in living kidney donors than in the general US population. Its disproportionate impact on minorities, non-citizens, and the less well educated is greater than that in the general population. PMID- 22050217 TI - Role of melatonin in the prevention of morphine-induced hyperalgesia and spinal glial activation in rats: protein kinase C pathway involved. AB - PURPOSES: Morphine can induce tolerance and hyperalgesia after long-term administration. Glial activation is believed to cause and maintain a state of morphine-induced pain hypersensitivity. The present study examines the effect of melatonin on tolerance, hyperalgesia, and reactive gliosis induced by morphine in rats. METHODS: The study examines the effect of melatonin on morphine-induced hyperalgesia using tail-flick test. Immunohistochemistry and Western blot was performed to investigate the expression of glial fibrillary acidic protein (GFAP) indicative of spinal glial activity. This study also measures protein kinase C (PKC) activity and cyclic adenosine monophosphate (cAMP) levels in spinal cords to investigate the mechanisms which melatonin involved. RESULTS: When coadministered intragastrically (i.g.) with morphine, melatonin in doses of 50 or 100 mg/kg significantly prevented hyperalgesia after termination of morphine. Immunohistochemistry and Western blot with GFAP revealed that melatonin significantly decreased morphine-induced over-expression of GFAP in spinal cord (p < .05). By measuring PKC activity and cAMP levels, the upregulated PKC activity and cAMP levels induced by morphine were significantly inhibited by melatonin. CONCLUSIONS: Melatonin can prevent morphine-withdrawal-induced hyperalgesia and glial reactivity. This effect of melatonin after morphine administration may mediated by inhibiting PKC activity and cAMP upregulation. PMID- 22050218 TI - Surfactant-free, large-scale, solution-liquid-solid growth of gallium phosphide nanowires and their use for visible-light-driven hydrogen production from water reduction. AB - Colloidal GaP nanowires (NWs) were synthesized on a large scale by a surfactant free, self-seeded solution-liquid-solid (SLS) method using triethylgallium and tris(trimethylsilyl)phosphine as precursors and a noncoordinating squalane solvent. Ga nanoscale droplets were generated in situ by thermal decomposition of the Ga precursor and subsequently promoted the NW growth. The GaP NWs were not intentionally doped and showed a positive open-circuit photovoltage based on photoelectrochemical measurements. Purified GaP NWs were used for visible-light driven water splitting. Upon photodeposition of Pt nanoparticles on the wire surfaces, significantly enhanced hydrogen production was observed. The results indicate that colloidal surfactant-free GaP NWs combined with potent surface electrocatalysts could serve as promising photocathodes for artificial photosynthesis. PMID- 22050219 TI - Onychodermis (specialized nail mesenchyme) containing onychofibroblasts in horizontal sections of the nail unit. PMID- 22050220 TI - Unexpected C-C bond cleavage: synthesis of 1,2,4-oxadiazol-5-ones from amidoximes with pentafluorophenyl or trifluoromethyl anion acting as leaving group. AB - An unexpected C-C bond cleavage has been observed on pentafluorobenzoylamidoximes under mild basic conditions. This observation has been exploited to develop a new synthesis of 1,2,4-oxadiazol-5-ones from amidoximes using pentafluorobenzoyl chloride or trifluoroacetic anhydride (TFAA) as a double acylating agent. The pentafluorophenyl anion and the trifluoromethyl anion acted as leaving groups in this transformation. PMID- 22050221 TI - Application of the UV laser printing technique to soft gelatin capsules containing titanium dioxide in the shells. AB - AIM: The purpose of this study was to examine application of ultraviolet (UV) laser irradiation to printing soft gelatin capsules containing titanium dioxide (TiO(2)) in the shells and to study effect of UV laser power on the color strength of printing on the soft gelatin capsules. METHODS: Size 6 Oval type soft gelatin capsules of which shells contained 0.685% TiO(2) and 0.005% ferric dioxide were used in this study. The capsules were irradiated pulsed UV laser at a wavelength 355 nm. The color strength of the printed capsules was determined by a spectrophotometer as total color difference (dE). RESULTS: The soft gelatin capsules which contained TiO(2) in the shells could be printed gray by the laser. Many black particles, which were associated with the printing, were formed at the colored parts of the shells. It was found that there were two inflection points in relationship between output laser energy of a pulse and dE. Below the lower point, the capsules were not printed. From the lower point to the upper point, the capsules were printed gray and total color difference of the printing increased linearly in proportion with the output laser energy. Beyond the upper point, total color difference showed saturation because of micro-bubbles formation at the laser irradiated spot. CONCLUSIONS: Soft gelatin capsules containing TiO(2) in the shells could be performed stable printing using the UV laser printing technique. Color strength of the printing could be controlled by regulating the laser energy between the two inflection points. PMID- 22050222 TI - Squalene monooxygenase - a target for hypercholesterolemic therapy. AB - Squalene monooxygenase catalyzes the epoxidation of C-C double bond of squalene to yield 2,3-oxidosqualene, the key step of sterol biosynthesis pathways in eukaryotes. Sterols are essential compounds of these organisms and squalene epoxidation is an important regulatory point in their synthesis. Squalene monooxygenase downregulation in vertebrates and fungi decreases synthesis of cholesterol and ergosterol, respectively, which makes squalene monooxygenase a potent and attractive target of hypercholesterolemia and antifungal therapies. Currently some fungal squalene monooxygenase inhibitors (terbinafine, naftifine, butenafine) are in clinical use, whereas mammalian enzymes' inhibitors are still under investigation. Research on new squalene monooxygenase inhibitors is important due to the prevalence of hypercholesterolemia and the lack of both sufficient and safe remedies. In this paper we (i) review data on activity and the structure of squalene monooxygenase, (ii) present its inhibitors, (iii) compare current strategies of lowering cholesterol level in blood with some of the most promising strategies, (iv) underline advantages of squalene monooxygenase as a target for hypercholesterolemia therapy, and (v) discuss safety concerns about hypercholesterolemia therapy based on inhibition of cellular cholesterol biosynthesis and potential usage of squalene monooxygenase inhibitors in clinical practice. After many years of use of statins there is some clinical evidence for their adverse effects and only partial effectiveness. Currently they are drugs of choice but are used with many restrictions, especially in case of children, elderly patients and women of childbearing potential. Certainly, for the next few years, statins will continue to be a suitable tool for cost-effective cardiovascular prevention; however research on new hypolipidemic drugs is highly desirable. We suggest that squalene monooxygenase inhibitors could become the hypocholesterolemic agents of the future. PMID- 22050223 TI - Cysteine proteinase SpeB from Streptococcus pyogenes - a potent modifier of immunologically important host and bacterial proteins. AB - Group A streptococcus (Streptococcus pyogenes) is an exclusively human pathogen that causes a wide spectrum of diseases ranging from pharyngitis, to impetigo, to toxic shock, to necrotizing fasciitis. The diversity of these disease states necessitates that S. pyogenes possess the ability to modulate both the innate and adaptive immune responses. SpeB, a cysteine proteinase, is the predominant secreted protein from S. pyogenes. Because of its relatively indiscriminant specificity, this enzyme has been shown to degrade the extracellular matrix, cytokines, chemokines, complement components, immunoglobulins, and serum protease inhibitors, to name but a few of the known substrates. Additionally, SpeB regulates other streptococcal proteins by degrading them or releasing them from the bacterial surface. Despite the wealth of literature on putative SpeB functions, there remains much controversy about this enzyme because many of reported activities would produce contradictory physiological results. Here we review all known host and bacterial protein substrates for SpeB, their cleavage sites, and discuss the role of this enzyme in streptococcal pathogenesis based on the current literature. PMID- 22050224 TI - S-Glucuronidation of 7-mercapto-4-methylcoumarin by human UDP glycosyltransferases in genetically engineered fission yeast cells. AB - Human UDP glycosyltransferases (UGTs) play an important role in xenobiotic detoxification. They increase the solubility of their substrates by adding a sugar moiety (such as glucuronic acid) to different functional entities (such as hydroxyl groups). The aim of this study was to investigate how glucuronidation of a standard substrate is affected by a change of the hetero-atom at the conjugation site. For this purpose, we compared the in vitro glucuronidation rates of 4-methylumbelliferone and 7-mercapto-4-methylcoumarin, respectively. Human liver microsomes catalyzed the S-glucuronidation of 7-mercapto-4- methylcoumarin almost as efficient as the O-glucuronidation of 4 methylumbelliferone. When testing isoenzyme specificity by whole cell biotransformation with fission yeast strains that recombinantly express all 19 human members of the UGT1 and UGT2 families, it was found that 13 isoenzymes were able to glucuronidate 7-mercapto-4-methylcoumarin, with five of them being specific for this substrate and the other eight also converting 4 methylumbelliferone under these conditions. The remaining six UGTs did not accept either substrate. Out of the eight isoenzymes that glucuronidated both substrates, four catalyzed both reactions approximately to the same extent, while three displayed higher conversion rates towards 4-methylumbelliferone and one preferred 7-mercapto-4-methylcoumarin. These data suggest that 7-mercapto-4 methylcoumarin is a convenient new standard substrate for monitoring S glucuronidation. PMID- 22050225 TI - Dimerization of human 5-lipoxygenase. AB - Human 5-lipoxygenase (5-LO) can form dimers as shown here via native gel electrophoresis, gel filtration chromatography and LILBID (laser induced liquid bead ion desorption) mass spectrometry. After glutathionylation of 5-LO by diamide/glutathione treatment, dimeric 5-LO was no longer detectable and 5-LO almost exclusively exists in the monomeric form which showed full catalytic activity. Incubation of 5-LO with diamide alone led to a disulfide-bridged dimer and to oligomer formation which displays a strongly reduced catalytic activity. The bioinformatic analysis of the 5-LO surface for putative protein-protein interaction domains and molecular modeling of the dimer interface suggests a head to tail orientation of the dimer which also explains the localization of previously reported ATP binding sites. This interface domain was confirmed by the observation that 5-LO dimer formation and inhibition of activity by diamide was largely prevented when four cysteines (C159S, C300S, C416S, C418S) in this domain were mutated to serines. PMID- 22050226 TI - Cloning, expression, characterization and inhibition studies on trypanothione synthetase, a drug target enzyme, from Leishmania donovani. AB - Trypanothione synthetase, a validated drug target, synthesizes trypanothione from glutathione and spermidine. Here we report the gene cloning, expression, characterization and inhibition studies of trypanothione synthetase from Leishmania donovani (LdTryS). The purified recombinant LdTryS enzyme obeyed Michaelis-Menten kinetics. High substrate inhibition was observed with glutathione (K(m)=33.24 MUm, k(cat)=1.3 s(-1), K(i)=866 MUm). The enzyme shows simple hyperbolic kinetics with fixed glutathione concentration and with other substrates limiting K(m) values for Mg. ATP and spermidine of 14.2 MUm and 139.6 MUm, respectively. LdTryS was also screened for inhibitors. Tomatine, conessine, uvaol and betulin were identified as inhibitors of the enzyme and were tested for leishmanicidal activity. Finally, the effect of LdTryS inhibitors on redox homeostasis of the parasite gives a broader picture of their action against leishmaniasis. PMID- 22050227 TI - Glucagon counteracts interleukin-6-dependent gene expression by redundant action of Epac and PKA. AB - Inflammation is the biological response to injurious stimuli. In the initial phase of the inflammatory process, interleukin-6 (IL-6) is the main inducer of acute phase protein expression in the liver. A prolonged acute phase response is characterised by a disturbed glucose homeostasis and elevated levels of IL-6, insulin, and counterregulatory hormones such as glucagon. Several studies deal with the impact of IL-6 on glucagon-dependent gene expression. In contrast, only very little is known about the influence of G-protein-coupled receptors on IL-6 signalling. Therefore, the aim of this study is to elucidate the regulation of IL 6-induced gene expression by glucagon. We could reveal a novel mechanism of negative regulation of IL-6-induced MAP kinase activation by glucagon in primary murine hepatocytes. IL-6-dependent induction of the ERK-dependent target gene Tfpi2, coding for a Kunitz-type serine protease inhibitor, was strongly down regulated by glucagon treatment. Studying the underlying mechanism revealed a redundant action of the signalling molecules exchange protein activated by cyclic AMP (Epac) and protein kinase A. The metabolic hormone glucagon interferes in IL 6-induced gene expression. This observation is indicative for a regulatory role of G-protein-coupled receptors in the IL-6-dependent inflammatory response. PMID- 22050228 TI - The influenza virus PB1-F2 protein has interferon antagonistic activity. AB - PB1-F2 is a nonstructural protein of influenza viruses encoded by the PB1 gene segment from a +1 open reading frame. It has been shown that PB1-F2 contributes to viral pathogenicity, although the underlying mechanisms are still unclear. Induction of type I interferon (IFN) and the innate immune response are the first line of defense against viral infection. Here we show that influenza A viruses (IAVs) lacking the PB1-F2 protein induce an enhanced expression of IFN-beta and IFN-stimulated genes in infected epithelial cells. Studying molecular mechanisms underlying the PB1-F2-mediated IFN antagonistic activity showed that PB1-F2 interferes with the RIG-I/MAVS protein complex thereby inhibiting the activation of the downstream transcription factor IFN regulatory factor 3. These findings were also reflected in in vivo studies demonstrating that infection with PR8 wild type (wt) virus resulted in higher lung titers and a more severe onset of disease compared with infection with its PB1-F2-deficient counterpart. Accordingly, a much more pronounced infiltration of lungs with immune cells was detected in mice infected with the PB1-F2 wt virus. In summary, we demonstrate that the PB1-F2 protein of IAVs exhibits a type I IFN-antagonistic function by interfering with the RIG-I/MAVS complex, which contributes to an enhanced pathogenicity in vivo. PMID- 22050229 TI - Somatotropic gene response to recombinant growth hormone treatment in buffalo leucocytes. AB - The use of recombinant bovine growth hormone (rbGH) to increase milk yield in cows is banned in some countries. In others, where it is authorised, it has triggered harsh debates on labelling of dairy products. If many studies have been performed on bovines, there is a lack of information on buffaloes, which are sometimes treated with rbGH and re-present an important economical resource for dairy products in some countries. Analytical methods with legal value for surveillance of rbGH treatments do not yet exist. Research on gene expression biomarkers is one of the most promising approaches to this purpose. For this reason, we treated five buffaloes for 10 weeks with a sustained-release formulation of rbGH and analysed the response of 20 somatotropic axis genes in leucocytes by real-time polymerase chain reaction. Overall changes in gene expression levels were of low magnitude and sometimes affected by the 'time' factor. Only the IGFBP-1 gene showed a significant under-expression (about two fold; p <0.001) in treated animals. Taken together, these results give evidence that expression analysis of the somatotropic axis genes in leucocytes is little helpful for discrimination of rbGH-treated buffaloes, but do not exclude that another array of genes could provide useful patterns of variation. PMID- 22050230 TI - Ammonia increases nitric oxide, free Zn(2+), and metallothionein mRNA expression in cultured rat astrocytes. AB - Ammonia is a major player in the pathogenesis of hepatic encephalopathy (HE) and affects astrocyte function by triggering a self-amplifying cycle between osmotic and oxidative stress. We recently demonstrated that hypoosmotic astrocyte swelling rapidly stimulates nitric oxide (NO) production and increases intracellular free Zn(2+) concentration ([Zn(2+)](i)). Here we report effects of ammonia on [Zn(2+)](i) homeostasis and NO synthesis. In cultured rat astrocytes, NH(4)Cl (5 mm) increased within 6 h both cytosolic and mitochondrial [Zn(2+)]. The [Zn(2+)](i) increase was transient and was mimicked by the nonmetabolizable CH(3)NH(3)Cl, and it was dependent on NO formation, as evidenced by the sensitivity toward the nitric oxide synthase inhibitor N(G)-monomethyl-l arginine. The NH(4)Cl-induced NO formation was sensitive to the Ca(2+) chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester and increases in both NO and [Zn(2+)](i) were blocked by the N-methyl-d aspartate receptor antagonist MK-801. The NH(4)Cl-triggered increase in [Zn(2+)](i) was followed by a Zn(2+)-dependent nuclear appearance of the metal response element-binding transcription factor and metallothionein messenger RNA (mRNA) induction. Metallothionein mRNA was also increased in vivo in rat cerebral cortex 6 h after an NH(4)Ac challenge. NH(4)Cl increased peripheral-type benzodiazepine receptor (PBR) protein expression, whereas PBR mRNA levels were decreased in a Zn(2+)-independent manner. The Zn(2+)-dependent upregulation of metallothionein following ammonia intoxication may reflect a cytoprotective response, whereas the increase in PBR expression may augment HE development. PMID- 22050231 TI - Expression pattern of cathepsin W isoforms in peripheral blood and gastroesophageal mucosa of patients with gastroesophageal reflux disease. AB - Cathepsin W is exclusively expressed in immune cells, and a novel isoform was identified previously. To characterize the expression pattern of the wildtype and isoform Ins10, specific polymerase chain reaction assays were generated and used to study respective transcript levels in peripheral blood cells and gastric biopsies in healthy subjects. The wildtype-encoding transcript levels were 3- and 9-fold higher in mucosal samples and peripheral immune cells, respectively (p<0.05). The predominant expression of wildtype form by infiltrating immune cells was confirmed in 116 patients with gastroesophageal reflux disease and 27 reflux-negative individuals demonstrating that cathepsin W expression is not altered in this disease. PMID- 22050233 TI - Review--Interactions between diatoms and stainless steel: focus on biofouling and biocorrosion. AB - There is a considerable body of information regarding bacterially enhanced corrosion, however, this review focuses on diatoms (unicellular algae) whose contribution to biocorrosion is less well studied. The reasons why diatoms have been neglected in studies of biocorrosion in natural waters are discussed and the question whether diatoms should be considered as inert with respect of electrochemical processes is considered. A particular focus is given to the case of stainless steels (SS), which are widely used in variety of applications in natural waters. Basic information on the cell biology of diatoms is included in the review, particularly with respect to their ability to 'sense' and adhere to surfaces. Investigations at the nanoscale are reviewed as these studies provide information about the behavior of cells at interfaces. Recent advances include the use of atomic force microscopy (AFM), although only a few studies have been applied to diatoms. Regarding the electrochemical behavior of SS, the mechanisms by which diatoms influence the potential ennoblement process is discussed. Such studies reveal the association of diatoms, in addition to bacteria, with biocorrosion processes. PMID- 22050234 TI - Reassessing the human health benefits from cleaner air. AB - Recent proposals to further reduce permitted levels of air pollution emissions are supported by high projected values of resulting public health benefits. For example, the Environmental Protection Agency recently estimated that the 1990 Clean Air Act Amendment (CAAA) will produce human health benefits in 2020, from reduced mortality rates, valued at nearly $2 trillion per year, compared to compliance costs of $65 billion ($0.065 trillion). However, while compliance costs can be measured, health benefits are unproved: they depend on a series of uncertain assumptions. Among these are that additional life expectancy gained by a beneficiary (with median age of about 80 years) should be valued at about $80,000 per month; that there is a 100% probability that a positive, linear, no threshold, causal relation exists between PM(2.5) concentration and mortality risk; and that progress in medicine and disease prevention will not greatly diminish this relationship. We present an alternative uncertainty analysis that assigns a positive probability of error to each assumption. This discrete uncertainty analysis suggests (with probability >90% under plausible alternative assumptions) that the costs of CAAA exceed its benefits. Thus, instead of suggesting to policymakers that CAAA benefits are almost certainly far larger than its costs, we believe that accuracy requires acknowledging that the costs purchase a relatively uncertain, possibly much smaller, benefit. The difference between these contrasting conclusions is driven by different approaches to uncertainty analysis, that is, excluding or including discrete uncertainties about the main assumptions required for nonzero health benefits to exist at all. PMID- 22050235 TI - Amelanotic melanoma: a detailed morphologic analysis with clinicopathologic correlation of 75 cases. AB - Amelanotic melanoma can have a varied appearance both clinically and microscopically. Here, we present our experiences with 75 cases of amelanotic melanoma defined clinically as a non-pigmented lesion and histopathologically as a tumor lacking significant melanization. We evaluated microscopic features such as morphology, mitotic count, nuclear atypia and presence of solar elastosis. Our amelanotic melanomas exhibited the following morphology: epitheloid (72%), spindled (18.7%) or desmoplastic (5.3%). In addition, we obtained patient information and clinical presentations on most of the cases (74/75; 98.7%) and follow-up data on 40% (30/75) of the cases. The majority of amelanotic melanomas in men were found on the trunk (13/45; 29%), head and neck (12/45; 26.7%), and lower limb (13/45; 29%) and in women were found on the lower limb (12/30; 40%), upper limb (10/30; 33.3%) and head and neck (6/30; 20%). In addition, we found that an increase in mitotic index correlated with worse survival (p < 0.026), whereas there were no differences in survival for other pathological features, such as nuclear atypia or solar elastosis. Furthermore, in cases with available tissue, all amelanotic melanoma expressed microphthalmia-associated transcription factor and tyrosinase, suggesting that the tumor cells retained melanocytic lineage and an enzyme in melanin formation, respectively. As the occurrence of amelanotic melanoma and the expression melanoma markers were similar to pigmented melanoma, we favor that amelanotic melanoma represents a subtype of melanoma rather than poorly differentiated or de-differentiated melanoma. PMID- 22050236 TI - Transient innermolecular carbene-hemicarcerand complex of fluorophenylcarbene. AB - Laser flash photolysis of fluorophenyldiazirine incarcerated in hemicarcerand 2 affords incarcerated fluorophenylcarbene [2?3], which forms a metastable, innermolecular pi-complex with aryl moieties of 2. This carbene complex can be observed spectroscopically. Extensive computational studies provide insights into the structure, spectroscopy, energetics, and kinetics of the 2?3 carbene complex. PMID- 22050237 TI - Iodide, azide, and cyanide complexes of (N,C), (N,N), and (N,O) metallacycles of tetra- and pentavalent uranium. AB - In contrast to the neutral macrocycle [UN*(2)(N,C)] (1) [N* = N(SiMe(3))(3); N,C = CH(2)SiMe(2)N(SiMe(3))] which was quite inert toward I(2), the anionic bismetallacycle [NaUN*(N,C)(2)] (2) was readily transformed into the enlarged monometallacycle [UN*(N,N)I] (4) [N,N = (Me(3)Si)NSiMe(2)CH(2)CH(2)SiMe(2)N(SiMe(3))] resulting from C-C coupling of the two CH(2) groups, and [NaUN*(N,O)(2)] (3) [N,O = OC(?CH(2))SiMe(2)N(SiMe(3))], which is devoid of any U-C bond, was oxidized into the U(V) bismetallacycle [Na{UN*(N,O)(2)}(2)(MU-I)] (5). Sodium amalgam reduction of 4 gave the U(III) compound [UN*(N,N)] (6). Addition of MN(3) or MCN to the (N,C), (N,N), and (N,O) metallacycles 1, 4, and 5 led to the formation of the anionic azide or cyanide derivatives M[UN*(2)(N,C)(N(3))] [M = Na, 7a or Na(15-crown-5), 7b], M[UN*(2)(N,C)(CN)] [M = NEt(4), 8a or Na(15-crown-5), 8b or K(18-crown-6), 8c], M[UN*(N,N)(N(3))(2)] [M = Na, 9a or Na(THF)(4), 9b], [NEt(4)][UN*(N,N)(CN)(2)] (10), M[UN*(N,O)(2)(N(3))] [M = Na, 11a or Na(15-crown-5), 11b], M[UN*(N,O)(2)(CN)] [M = NEt(4), 12a or Na(15-crown-5), 12b]. In the presence of excess iodine in THF, the cyanide 12a was converted back into the iodide 5, while the azide 11a was transformed into the neutral U(V) complex [U(N{SiMe(3)}SiMe(2)C{CHI}O)(2)I(THF)] (13). The X-ray crystal structures of 4, 7b, 8a-c, 9b, 10, 12b, and 13 were determined. PMID- 22050238 TI - Inherited neuromuscular disorders: pathway to diagnosis. AB - Muscle weakness in childhood can be caused by a lesion at any point extending from the motor cortex, brainstem and spinal cord to the anterior horn cell, peripheral nerve, neuromuscular junction and muscle. A comprehensive history and physical examination is essential to aid classification of the neuromuscular disorder and direct gene testing. The more common disorders such as spinal muscular atrophy, Duchenne muscular dystrophy, myotonic dystrophy and facioscapulohumeral dystrophy may be diagnosed on direct gene testing based on the history and clinical examination. The congenital myopathies are classified based on structural abnormalities on muscle biopsy, while protein abnormalities on immunohistochemistry and immunoblotting aid classification of the muscular dystrophies. In this review, we provide an approach to diagnosis of a child with weakness, with a focus on the inherited neuromuscular disorders, and the features on history, examination and investigation that help to distinguish between them. PMID- 22050239 TI - Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe. AB - BACKGROUND: The prevalence of asthma and its association with chronic rhinosinusitis (CRS) have not been widely studied in population-based epidemiological surveys. METHODS: The Global Allergy and Asthma Network of Excellence (GA(2) LEN) conducted a postal questionnaire in representative samples of adults living in Europe to assess the presence of asthma and CRS defined by the European Position Paper on Rhinosinusitis and Nasal Polyps. The prevalence of self-reported current asthma by age group was determined. The association of asthma with CRS in each participating centre was assessed using logistic regression analyses, controlling for age, sex and smoking, and the effect estimates were combined using standard methods of meta-analysis. RESULTS: Over 52,000 adults aged 18-75 years and living in 19 centres in 12 countries took part. In most centres, and overall, the reported prevalence of asthma was lower in older adults (adjusted OR for 65-74 years compared with 15-24 years: 0.72; 95% CI: 0.63-0.81). In all centres, there was a strong association of asthma with CRS (adjusted OR: 3.47; 95% CI: 3.20-3.76) at all ages. The association with asthma was stronger in those reporting both CRS and allergic rhinitis (adjusted OR: 11.85; 95% CI: 10.57-13.17). CRS in the absence of nasal allergies was positively associated with late-onset asthma. CONCLUSION: Geographical variation in the prevalence of self-reported asthma was observed across Europe, but overall, self reported asthma was more common in young adults, women and smokers. In all age groups, men and women, and irrespective of smoking behaviour, asthma was also associated with CRS. PMID- 22050240 TI - Increased prokineticin 2 expression in gut inflammation: role in visceral pain and intestinal ion transport. AB - BACKGROUND: Prokineticin 2 (PROK2) is an inflammatory cytokine-like molecule expressed predominantly by macrophages and neutrophils infiltrating sites of tissue damage. Given the established role of prokineticin signaling on gastrointestinal function, we have explored Prok2 gene expression in inflammatory conditions of the gastrointestinal tract and assessed the possible consequences on gut physiology. METHODS: Prokineticin expression was examined in normal and colitic tissues using qPCR and immunohistochemistry. Functional responses to PROK2 were studied using calcium imaging and a novel antagonist, Compound 3, used to determine the role of PROK2 and prokineticin receptors in inflammatory visceral pain and ion transport. KEY RESULTS: Prok2 gene expression was up regulated in biopsy samples from ulcerative colitis patients, and similar elevations were observed in rodent models of inflammatory colitis. Prokineticin receptor 1 (PKR1) was localized to the enteric neurons and extrinsic sensory neurons, whereas Pkr2 expression was restricted to sensory ganglia. In rats, PROK2-increased intracellular calcium levels in cultured enteric and dorsal root ganglia neurons, which was blocked by Compound 3. Moreover, PROK2 acting at prokineticin receptors stimulated intrinsic neuronally mediated ion transport in rat ileal mucosa. In vivo, Compound 3 reversed intracolonic mustard oil-induced referred allodynia and TNBS-induced visceral hypersensitivity, but not non inflammatory, stress-induced visceral pain. CONCLUSIONS & INFERENCES: Elevated Prok2 levels, as a consequence of gastrointestinal tract inflammation, induce visceral pain via prokineticin receptors. This observation, together with the finding that PROK2 can modulate intestinal ion transport, raises the possibility that inhibitors of PROK2 signaling may have clinical utility in gastrointestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease. PMID- 22050241 TI - Presentation of two cases of immediate restoration of implants in the esthetic region, using facilitate software and guides with stereolithographic model surgery prior to patient surgery. AB - Improvements in both implant microsurfaces and placement techniques have reduced healing time and increased survival rates. CAD/CAM technology and improved ceramic materials allow for achievement of improved esthetics at the implant restoration level. Two clinical procedures have the capacity to decrease patient postoperative discomfort and improve esthetics. Flapless surgery reduces surgical trauma and postoperative problems. Placement of the final prosthetic abutment at the time of implant placement stabilizes soft tissue adhesion and position to the implant. Both results require careful presurgical planning with precise implant and abutment placement. This is a clinical report of two cases that are part of a larger ongoing clinical trial of 20 patients. The inclusion criterion was that patients should be missing a single tooth in the esthetic zone. FacilitateTM software was used in conjunction with dicom files transferred from CT scans for diagnosis. Stereolithographic models and surgical guides were fabricated from the digital information. Surgical guides were used preoperatively so implant replicas could be placed in stereolithographic models as simulated surgery. A ZirDesignTM ceramic abutment was adapted on the model, and a provisional crown was fabricated. At the time of actual implant surgery, the same surgical guide was used with a flapless approach. The previously modified ceramic abutment was screw retained and torqued to place into the implant. The provisional crown was then cemented after blocking out the screw access hole. A final restoration was fabricated from all-ceramic material after several months. Success requires careful patient selection and attention to each step of the technique. Preliminary outcomes from the ongoing clinical trial are promising. PMID- 22050242 TI - Retrospective audit of postictal generalized EEG suppression in telemetry. AB - Sudden unexpected death in epilepsy (SUDEP) has on rare occasions occurred during electroencephalography (EEG) telemetry, and in such cases postictal EEG suppression (PI EEG-SUP) was frequently observed. More recently a retrospective case-control study reported this pattern as a risk factor for SUDEP. We retrospectively audited frequency and electroclinical features of this pattern as well as immediate management following tonic-clonic seizures during telemetry. Forty-eight patients with tonic-clonic seizures were identified from 470 consecutive EEG-videotelemetry reports. Thirteen patients (27%) with PI EEG-SUP (mean duration 38.1 s, range 6-69 s, median 38 s) were compared to 12 randomly selected controls. One seizure was analyzed per individual. Those with PI EEG-SUP were significantly more likely to be motionless after the seizure and have simple nursing interventions performed (suction, oxygen administration, placed in recovery position, vital signs checked). This pattern is relatively common and requires further study as a potential marker for increased mortality in epilepsy. PMID- 22050243 TI - Simulating pH titration of a single surfactant in ionic and nonionic surfactant micelles. AB - Calculation of surfactant pK(a)'s in micelles is a challenging task using traditional electrostatic methods due to the lack of structural data and information regarding the effective dielectric constant. Here we test the implicit- and hybrid-solvent-based continuous constant pH molecular dynamics (CpHMD) methods for predicting the pK(a) shift of a lauric acid solubilized in three micelles: dodecyl sulfate (DS), dodecyltrimethylammonium (DTA), and dodecyltriethylene glycol ether (DE3). Both types of simulations are able to reproduce the observed positive pK(a) shifts for the anionic DS and nonionic DE3 micelles. However, for the cationic DTA micelle, the implicit-solvent simulation fails to predict the direction of the pK(a) shift, while the hybrid-solvent simulation, where conformational sampling is conducted in explicit solvent, is consistent with experiment, although the specific-ion effects remain to be accurately determined. Comparison between the implicit- and hybrid-solvent data shows that the latter gives a more realistic description of the conformational environment of the titrating probe. Surprisingly, in the DTA micelle, surfactants are only slightly attracted to the laurate ion, which diminishes the magnitude of the electrostatic stabilization, resulting in a positive pK(a) shift that cannot be explained by chemical intuition or other theoretical models. Our data underscores the importance of microscopic models and ionization-coupled conformational dynamics in quantitative prediction of the pK(a) shifts in micelles. PMID- 22050244 TI - Boundary condition effects on maximum groundwater withdrawal in coastal aquifers. AB - Prevention of sea water intrusion in coastal aquifers subject to groundwater withdrawal requires optimization of well pumping rates to maximize the water supply while avoiding sea water intrusion. Boundary conditions and the aquifer domain size have significant influences on simulating flow and concentration fields and estimating maximum pumping rates. In this study, an analytical solution is derived based on the potential-flow theory for evaluating maximum groundwater pumping rates in a domain with a constant hydraulic head landward boundary. An empirical correction factor, which was introduced by Pool and Carrera (2011) to account for mixing in the case with a constant recharge rate boundary condition, is found also applicable for the case with a constant hydraulic head boundary condition, and therefore greatly improves the usefulness of the sharp-interface analytical solution. Comparing with the solution for a constant recharge rate boundary, we find that a constant hydraulic head boundary often yields larger estimations of the maximum pumping rate and when the domain size is five times greater than the distance between the well and the coastline, the effect of setting different landward boundary conditions becomes insignificant with a relative difference between two solutions less than 2.5%. These findings can serve as a preliminary guidance for conducting numerical simulations and designing tank-scale laboratory experiments for studying groundwater withdrawal problems in coastal aquifers with minimized boundary condition effects. PMID- 22050245 TI - Radiologic case study. PMID- 22050246 TI - Inaccurate histological documentation of massive desmoplastic fibroblastoma with scapular invasion. PMID- 22050247 TI - Identifying multiple reports from the same study. PMID- 22050248 TI - 54-year follow-up of lumbar posterior fusion with tibial graft. PMID- 22050249 TI - Merger mania: a sign of the times or typical market maturation? PMID- 22050250 TI - Arthroscopically assisted conversion of total shoulder arthroplasty to hemiarthroplasty with glenoid bone grafting. AB - Aseptic loosening of the glenoid component after total shoulder arthroplasty presents a considerable treatment challenge in the setting of substantial glenoid bone loss. Glenoid component explantation and bone grafting of defects have become common methods of recreating bone stock in hopes of preventing later fractures, maintaining joint kinematics, and allowing for later glenoid reimplantation if necessary. Although this has been traditionally accomplished via open techniques, this article describes an arthroscopic-assisted method of glenoid explantation and bone grafting for cases of aseptic glenoid loosening with contained bone defects. PMID- 22050251 TI - Overuse injuries in youth throwing athletes. PMID- 22050252 TI - Twitter as a communication tool for orthopedic surgery. AB - Twitter is a social networking Web site that has changed the way information is communicated. This study involved identifying, categorizing, and reviewing orthopedic Twitter profiles. A total of 412 profiles were identified. Of those, 176 (50.3%) were surgeons; 89 (50.5%) were based in the United States and 77 (43.8%) were not (10 unclassified). Most surgeons were young; 66% of surgeons were board certified within the past 10 years. Only a small percentage of orthopedic surgeons and practices currently use Twitter, but the use of social networking for orthopedic communication is likely to play an increasing role in future clinical practice. PMID- 22050253 TI - A review of the methods, interpretation, and limitations of the urine drug screen. AB - Toxicology screens are used to detect the presence of prescription, nonprescription, or illicit substances. These tests are used in emergency situations to detect intentional or accidental overdose, to monitor drug dependency, and to screen for medical or legal purposes. An initial immunoassay reports qualitative results based on established cut-off concentrations. As a screening test, the initial immunoassay is less sensitive and therefore must be interpreted in the context of confounding variables such as the testing method, the substance being screened, and patient-specific characteristics. Either gas chromatography or high-performance liquid chromatography can be used to confirm positive results. PMID- 22050254 TI - Subtle injuries to the lisfranc joint. AB - The tarsometatarsal joint complex is an osseous and capsuloligamentous network that includes the 5 metatarsals, their articulations with the cuneiforms and cuboid, and the Lisfranc ligament, a strong interosseous attachment between the medial cuneiform and second metatarsal. A multitude of injury patterns exist involving the tarsometatarsal joint complex; a Lisfranc injury does not delineate a specific injury, but instead a spectrum of processes involving the tarsometatarsal joint complex. PMID- 22050255 TI - Patient activation and functional recovery in persons undergoing spine surgery. PMID- 22050256 TI - Results of cervical arthroplasty compared with anterior discectomy and fusion: four-year clinical outcomes in a prospective, randomized controlled trial. PMID- 22050257 TI - Intrasubstance ruptures of the biceps brachii: diagnosis and management. AB - Traumatic intrasubstance ruptures of the biceps brachii are rare and historically specific to military static line parachute jumps; however, these injuries have recently been reported in the civilian literature. Diagnosis is made by history, clinical weakness in supination and elbow flexion, extensive ecchymosis and edema, and a palpable defect. Ultrasound and magnetic resonance imaging are useful to confirm the diagnosis and injury severity. Nonoperative treatment involves splinting in acute flexion. Percutaneous hematoma aspiration has been described. Early surgical intervention with primary repair has been shown to be more successful than late reconstruction. Studies comparing operative and nonoperative treatment are lacking. PMID- 22050259 TI - The new HLA allele, HLA-A*03:57, differs from HLA-A*03:01 by two amino acids at positions 76 and 77 in the alpha2 domain affecting the pocket F of the peptide binding groove. AB - HLA-A*03:57 has two amino acid exchanges in exon 2 at adjacent positions of the peptide-binding groove. PMID- 22050260 TI - Surgical revision of biliary strictures following adult live donor liver transplantation: patient selection, morbidity, and outcomes. AB - Biliary strictures after live donor liver transplantation (LDLT) are frequent and difficult to manage. The outcomes of surgical correction of biliary anastomotic complications remain unclear. Clinical outcomes of patients requiring surgical revision of their biliary anastomosis following LDLT were analyzed. Of 296 consecutive right lobe LDLTs, approximately 21% of patients developed biliary strictures. Of these patients, twelve required surgical revision of a biliary anastomotic stricture. For patients who had operative repair, the average time from transplantation to stricture diagnosis was 7.6 months. Mean time to surgical correction was 8.2 months from the time of stricture diagnosis. Eight of 12 (67%) patients no longer require any intervention with a mean follow-up of 43.7 months. Two of 12 patients require intermittent medical treatment for presumed cholangitis, but have not required biliary interventions. Two patients have required chronic PTC catheter drainage. The 30-day postoperative morbidity was 58%, with four serious (Grade 3) complications occurring in three patients. Early stricture repair (<6 months from diagnosis of stricture) and younger donor grafts were associated with better surgical outcomes. Timely surgical correction of biliary strictures is successful and durable in appropriately selected patients. However, operative repair is associated with significant postoperative morbidity. PMID- 22050261 TI - Maternal exposure to aqueous extract of Jacaranda decurrens: effects on reproductive system in male rats. AB - CONTEXT: Jacaranda decurrens subsp. symmetrifoliolata Farias & Proenca (Bignoniaceae) is a species widely used for their medicinal properties. At least to our known, no study has been conducted concerning its toxicological profile after gestational and lactational exposure. OBJECTIVE: The present study was carried out to evaluate the effects of J. decurrens on development of the reproductive system in male rats. MATERIALS AND METHODS: Pregnant rats were treated daily (gavage) with 250 or 500 mg/kg/day of aqueous extract of J. decurrens or vehicle, from day 12 of pregnancy to day 21 of lactation. RESULTS AND DISCUSSION: Both doses of J. decurrens significantly anticipated (p < 0.05) the age of testicular descent to the scrotum, a parameter indicative of puberty initiation. Furthermore, at puberty, there was a significant reduction (p < 0.05) in testicular and epididymis weights in the offspring exposed to the higher dose of extract, without effect on sperm production and the histology of reproductive organs. On the other hand, at adulthood, the reproductive parameters analyzed did not differ among groups. CONCLUSIONS: J. decurrens, in this experimental model, interfered with the initial development of the reproductive system, but without lasting effects on sperm production in adulthood. PMID- 22050262 TI - Understanding standard drinks and drinking guidelines. AB - INTRODUCTION AND AIMS: For consumers to follow drinking guidelines and limit their risk of negative consequences they need to track their ethanol consumption. This paper reviews published research on the ability of consumers to utilise information about the alcohol content of beverages when expressed in different forms, for example in standard drinks or units versus percentage alcohol content. DESIGN AND METHODS: A review of the literature on standard drink definitions and consumer understanding of these, actual drink pouring, use of standard drinks in guidelines and consumer understanding and use of these. RESULTS: Standard drink definitions vary across countries and typically contain less alcohol than actual drinks. Drinkers have difficulty defining and pouring standard drinks with over pouring being the norm such that intake volume is typically underestimated. Drinkers have difficulty using percentage alcohol by volume and pour size information in calculating intake but can effectively utilise standard drink labelling to track intake. Standard drink labelling is an effective but little used strategy for enabling drinkers to track their alcohol intake and potentially conform to safe or low-risk drinking guidelines. PMID- 22050263 TI - Exploring the binding sites of glycogen synthase kinase 3. Identification and characterization of allosteric modulation cavities. AB - Glycogen synthase kinase 3 (GSK-3) is an important drug target for human severe unmet diseases. Discovery and/or design of allosteric kinase modulators are gaining importance in this field not only for the increased selectivity of this kind of compounds but also for the subtle modulation of the target. This last point is of utmost importance for the GSK-3 inhibition as a therapeutic approach. GSK-3 activity is completely necessary for life, and only the aberrant overactivity found in the pathologies should be inhibited with its inhibitors treatment. We performed here a search for the druggable sites on the enzyme using the fpocket algorithm with the aim to provide allosteric potential binding sites on it and new clues for further drug discoveries. Moreover, our results allowed us to determine the binding sites of different GSK-3 ATP noncompetitive inhibitors, such as manzamine A and the new small molecule VP 0.7, providing evidence for potential allosteric inhibition of GSK-3. PMID- 22050264 TI - Dissolved organic carbon--a practical consideration in application of biotic ligand models in Chinese waters. PMID- 22050265 TI - Prevalence of temporomandibular disorders in a population of complete denture wearers. AB - BACKGROUND: Complete tooth loss among the elderly is still frequent in developing countries and the incidence of temporomandibular disorders (TMD) is a common finding in complete denture wearers. OBJECTIVES: The aim of this study was to evaluate the prevalence of temporomandibular disorders (TMD) in a population of complete denture wearers. MATERIALS AND METHODS: The data were collected by four examiners for the diagnosis of use and need for complete dentures followed by the World Health Organization standards and interviews for TMD signs and symptoms evaluation. Exploratory variables included demographic, socio-economic status and TMD prevalence. RESULTS: The prevalence of TMD among denture wearers was 55.12%. Chi-squared test showed no statistical difference between subjects with or without TMD for gender, geographical location and skin colour (p < 0.05). The number of subjects with TMD increased as the period of complete denture wear increased, although no statistical difference between groups were found (p < 0.05). CONCLUSIONS: There is a need of educational programmes aiming at the importance of health care and periodical change of a complete denture, and strategies with a preventive approach to quality general dental care. PMID- 22050266 TI - Pancreas transplantation after bariatric surgery. AB - Obese transplant candidates are at increased risk for perioperative and postoperative complications. In many transplant programs, morbid obesity is considered to be an exclusion criterion for transplantation. The only potential option that would grant these patients access to transplant is weight loss. Non operative weight loss strategies such as behavioral modifications, exercise, diet, or medication have only very limited success in achieving long-term weight loss. In contrast, bariatric surgery was shown to achieve not only more excessive weight loss, but more importantly, this weight loss can be sustained for longer periods of time. Therefore, bariatric surgery presents an attractive option for weight loss for morbidly obese transplant candidates. We report our experience with four patients who underwent bariatric surgery prior to successful pancreas transplantation. Even though gastric bypass and laparoscopic adjustable gastric band present as equivalent alternatives for weight reduction, we believe that in the population of morbidly obese diabetic patients who are possible candidates for pancreas transplantation, laparoscopic adjustable gastric band placement is the more suitable procedure. PMID- 22050267 TI - Plant-derived extracts in the neuroscience of anxiety on animal models: biases and comments. AB - Generalized anxiety disorders probably represent one of the world's biggest mental health problems. A large number of studies have also shown that anxiety disorders and depression are often associated with quality of life impairments. As anxiety represents a big concern in public health, a substantial literature supports clinically important associations between psychiatric illness and chronic medical conditions. Actually, most research focuses on depression, finding that depression can adversely affect self-care and increase the risk of incident medical illness, complications, and mortality. Anxiety disorders are less well studied, but robust epidemiological and clinical evidences show that they play an equally important role. Recent reported articles have raised a debate about the effectiveness of some plant-derived extracts in anxiety-like models in mice. Biases about several aspects related with experimental setting, animal selection, environments, operators and investigators, selection and performance of behavioral tests, controls, results managing, and statistics are here discussed. PMID- 22050268 TI - C-N bond cleavage of allylic amines via hydrogen bond activation with alcohol solvents in Pd-catalyzed allylic alkylation of carbonyl compounds. AB - Hydrogen-bond-activated C-N bond cleavage of allylic amines was realized in Pd catalyzed allylic alkylation to form the C-C bond product. The method could be expanded to a series of allylic amines and carbonyl compounds with excellent results. It provides a new and convenient access to C-C bond formation based on Pd-catalyzed allylic alkylation of allylic amines by using only inexpensive alcohol solvents. PMID- 22050269 TI - Intramolecular ester enolate-imine cyclization reactions for the asymmetric synthesis of polycyclic beta-lactams and cyclic beta-amino acid derivatives. AB - Enolates of chiral N-(alpha-methyl-p-methoxybenzyl)-omega-imino-esters undergo intramolecular cyclization reactions to afford (syn)-aza-anions of beta-amino esters in high dr that cyclize to afford N-(alpha-methyl-p-methoxybenzyl)-beta lactams that can be readily deprotected to afford their corresponding cyclic NH beta-lactams, beta-amino esters, or beta-amino acids. PMID- 22050270 TI - Combination treatment by 10 600 nm ablative fractional carbon dioxide laser and narrowband ultraviolet B in refractory nonsegmental vitiligo: a prospective, randomized half-body comparative study. AB - BACKGROUND: Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed. OBJECTIVES: To investigate the effects of fractional carbon dioxide (CO(2) ) laser therapy followed by systemic narrowband ultraviolet B (NB-UVB) phototherapy on nonsegmental vitiligo (NSV) as a prospective and randomized left-right comparative study. METHODS: Ten patients with NSV who presented symmetrical vitiligo lesions with no further improvement despite more than 1 year of conventional treatment were enrolled. Two sessions of half-body fractional CO(2) laser therapy were performed at a 2-month interval. NB UVB phototherapy was then administered to the entire body 5 days after each fractional laser treatment twice a week, increasing the dose incrementally by 15% at each session. Objective clinical assessments were made by two blinded dermatologists using a quartile grading scale, and the patients' overall satisfaction was evaluated using a 10-point visual analogue scale. RESULTS: Two months after the last treatment, mean improvement scores, assessed by physicians, were significantly higher for those treated with half-body fractional CO(2) laser therapy followed by NB-UVB phototherapy, compared with those treated with NB-UVB alone (P=0.034). In addition, according to subjective assessment, the half-body laser treatment followed by NB-UVB showed significantly higher improvements compared with NB-UVB treatment alone (P=0.023). Noticeable adverse events, such as infection, scarring and Koebner phenomenon, were not found in any patient. CONCLUSIONS: This study suggests that fractional CO(2) laser therapy followed by NB-UVB phototherapy could be used effectively and safely as an alternative modality for the treatment of refractory vitiligo. PMID- 22050271 TI - Prevalence of diagnosed and undiagnosed diabetes and hypertension in India- results from the Screening India's Twin Epidemic (SITE) study. AB - OBJECTIVE: Despite the rising number of patients with diabetes and hypertension in India, there is a dearth of nationwide, comprehensive prevalence data on these diseases. Our study aimed at collecting data on the prevalence of diabetes and hypertension and the underlying risk factors in various outpatient facilities throughout India. METHODS: This cross-sectional study was planned to be conducted in 10 Indian states, one state at a time. It was targeted to enroll about 2,000 patients from 100 centers in each state. Each center enrolled the first 10 patients (>=18 years of age, not pregnant, signed consent) per day on two consecutive days. "Diabetes" and "hypertension" were defined by the 2008 American Diabetes Association and the Joint National Committee's 7(th) Report guidelines, respectively. Patient data (demographics, lifestyle factors, medical history, and laboratory diagnostic results) were collected and analyzed. RESULTS: During 2009 2010, in total, 15,662 eligible patients (54.8% males; mean age, 48.9+/-13.9 years) from eight states were enrolled. Diabetes was prevalent in 5,427 (34.7%) patients, and 7,212 (46.0%) patients had hypertension. Diabetes and hypertension were coexistent in 3,227 (20.6%) patients. Among those whose disease status was not known at enrollment, 7.2% (793 of 11,028) and 22.2% (2,408 of 10,858) patients were newly diagnosed with diabetes and hypertension, respectively; additionally, 18.4% (2,031 of 11,028) were classified as having prediabetes and 60.1% (6,521 of 10,858) as having prehypertension. A positive association (P<0.05) was observed between diabetes/hypertension and age, familial history of either, a medical history of cardiovascular disorders, alcohol consumption, and diet. CONCLUSIONS: Our study demonstrates that the substantial burden of diabetes and hypertension is on the rise in India. Patient awareness and timely diagnosis and intervention hold the key to limiting this twin epidemic. PMID- 22050273 TI - Errata. PMID- 22050272 TI - Seventy-five years' Institute of Veterinary Pathology. PMID- 22050274 TI - ABM Clinical Protocol #24: Allergic Proctocolitis in the Exclusively Breastfed Infant. AB - A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. These guidelines are not intended to be all-inclusive, but to provide a basic framework for physician education regarding breastfeeding. PMID- 22050275 TI - Characterisation of Plasmodium falciparum aspartic protease inhibition by piperidine derivatives. AB - Piperidine derivatives are reported to exhibit a variety of pharmacological activities. In this article, synthesis and aspartic protease inhibitory activity of three nitrophenacyl derivatives of N-methyl-4-hydroxy piperidine are reported. Enzyme assays showed that the attachment of a nitro group in the benzene ring plays an important role in the inhibition of plasmepsin-II of Plasmodium falciparum. The compound 1-methyl-1-(4'-nitrophenacyl)-4-hydroxypiperidinium bromide (3), consisting of a nitro group at the para position, was the most active at the concentration of 1.0 uM. The activity of the compounds was evaluated through the observed orientation and diagrammatic representation of nitrophenacyl derivatives of 4-hydroxy piperidine. PMID- 22050276 TI - Robust allocation of a defensive budget considering an attacker's private information. AB - Attackers' private information is one of the main issues in defensive resource allocation games in homeland security. The outcome of a defense resource allocation decision critically depends on the accuracy of estimations about the attacker's attributes. However, terrorists' goals may be unknown to the defender, necessitating robust decisions by the defender. This article develops a robust optimization game-theoretical model for identifying optimal defense resource allocation strategies for a rational defender facing a strategic attacker while the attacker's valuation of targets, being the most critical attribute of the attacker, is unknown but belongs to bounded distribution-free intervals. To our best knowledge, no previous research has applied robust optimization in homeland security resource allocation when uncertainty is defined in bounded distribution free intervals. The key features of our model include (1) modeling uncertainty in attackers' attributes, where uncertainty is characterized by bounded intervals; (2) finding the robust-optimization equilibrium for the defender using concepts dealing with budget of uncertainty and price of robustness; and (3) applying the proposed model to real data. PMID- 22050277 TI - Synthesis and structural characterization of an unprecedented nonmetal cation polyborate salt containing two different "isolated" polyborate anions: [H2en]2[B4O5(OH)4][B7O9(OH)5].3H2O (en = H2NCH2CH2NH2). AB - The nonmetal cation polyborate salt of stoichiometry [H(2)en](2)[B(11)O(18)(OH)].7H(2)O is obtained from the reaction of 1,2 diaminoethane and boric acid (1:5 ratio) in H(2)O/MeOH. An X-ray crystallographic study of the product reveals that the polyborate moiety is composed of two isolated hydrated polyborate anions: [B(4)O(5)(OH)(4)](2-) and [B(7)O(9)(OH)(5)](2-). The structure is templated by the cations with the anions forming a supramolecular H-bonded network, augmented by additional H-bonds involving the waters of crystallization and the cations. PMID- 22050279 TI - Practical guide to skin prick tests in allergy to aeroallergens. AB - This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries. PMID- 22050280 TI - Quality of life assessment in breast cancer: when does it add prognostic value for survival? PMID- 22050281 TI - Excessive resections in breast-conserving surgery: a retrospective multicentre study. AB - The main determinant of cosmetic outcomes following breast-conserving surgery (BCS) for breast cancer is the volume of resection. The importance of achieving optimal oncological control may lead to an unnecessarily large resection of breast tissue. The aim of this study is to evaluate excess resection volume in BCS for cancer by determining a calculated resection ratio (CRR). This retrospective study was conducted in four affiliated institutions and involved 726 consecutive patients with T1-T2 invasive breast cancer treated by BCS between January 2006 and 2009. The pathology reports were reviewed for tumor palpability, tumor size, surgical specimen size, and oncological margin status. The optimal resection volume (ORV) was defined as the spherical tumor volume with an added 1.0 cm margin of healthy breast tissue. The total resection volume (TRV) was defined as the ellipsoid volume of the surgical specimen. CRR was determined by dividing the TRV by the ORV. Of all tumors, 72% (525/726) were palpable, and 28% (201/726) were nonpalpable. The tumor stage was T1 in 492 patients (67.8%) and T2 in 234 patients (32.2%). The median CRR was 2.5 (0.01-42.93). Margin status was positive or focally positive in 153 patients (21.1%). Lower tumor stage was associated with a higher CRR (factor 0.61 [p < 0.0001] and a lower positive margin rate [p = 0.064]). Accordingly, the median CRR of the nonpalpable lesions was higher than that of the palpable lesions (3.1 and 2.2, respectively; p < 0.01), and the involved margin rate was lower (17.4% and 22.5%, respectively; p = 0.13). Of patients with a CRR >4.0, 10.7% still had tumor involved margins. This study clearly shows that BCS is associated with excessive resection of healthy breast tissue while clear margins are not assured. Surgical factors should be modified to improve surgical accuracy. PMID- 22050282 TI - Treatment of early breast cancer, a long-term follow-up study: the GOCS experience. AB - Most cases of breast cancer are diagnosed at early stage of disease; therefore, treatment is oriented to increase the disease-free interval (DFI) and overall survival (OS). The prognosis, in comparison with other malignancies, has improved in the last decades as a result of mammographic screening. The aim of the study was to report the incidence of local and distant recurrence, DFI and OS in patients (pts) with stage I and stage II breast cancer over a period of 26 years divided into three groups. From January 1978 to December 2004, 927 women with early breast cancer (EBC) were included, 350 were stage I and 577 Stage II (AJCC 2002). Patients were divided according to the year of diagnosis into three periods of 10 years: Group A (1978-1987) 135 pts, Group B (1988-1997) 412 pts, and Group C (1998-2004) 380 pts. DFI was analyzed from the date of initial diagnosis to the date of local or distant recurrence. OS was estimated from the date of initial diagnosis to the last follow-up or date of death. Median age was 51 years (28-92). Conservative surgery was performed in 69% of pts, adjuvant radiation therapy in 78%, adjuvant chemotherapy in 29%, and adjuvant hormone therapy in 18%. The median follow-up was 8.4 years (0.3-30). The mean tumor size in Group A was 2.7 cm, in Group B 2.2 cm, and in Group C 1.94 cm (p = 0.0001). The percentage of pts with stage I increased from 13% in Group A to 38% in Group B and to 47% in Group C (p = 0.0001). Local recurrence was documented in 5% of all pts, whereas 28% developed metastatic disease. The DFI and OS showed a statistically significant difference among the three groups (p = 0.005). DFI rate at 5, 10, 15, 20, and 25 years was 71%, 67%, 65%, 65%, and 64%, respectively. OS at 5, 10, 15, 20, and 25 years was 82%, 62%, 49%, 39%, and 28%, respectively. Factors that had an effect in OS demonstrated by the multivariate regression analysis were: Tumor size, ER status, and nodal involvement (p < 0.001). Clinical outcomes in EBC in our experience are similar to those reported in international literature. The DFI and OS showed a statistically significant difference among the three groups. This group of pts continues to have a good prognosis as shown by the OS rate at 5, 10, 15, 20, and 25 years, although a high percentage of pts still to have recurrence and die from breast cancer after 5, 10, 15, 20, and 25 years of follow-up. PMID- 22050283 TI - Increasing coverage rates for mammographic screening in France in older women--16 years of follow-up. PMID- 22050284 TI - Electrochemical determination of pKa of N-bases in ionic liquid media. AB - Two electrochemical techniques have been used to measure the pK(a) of N-bases in several ionic liquids (ILs). The first method corresponds to a potentiometric titration of a strong acid with the N-base using a platinized Pt indicator electrode immersed in the IL solution and maintained under dihydrogen atmosphere via gas bubbling. The second approach involves performing cyclic voltammetry at a platinized Pt electrode in a solution containing both strong acid and the conjugate weak acid of the N-base. Values of pK(a) obtained by one or the other approach are in good agreement with each other. The experimental data clearly demonstrated that acid/base chemistry in ILs is similar to that observed in molecular nonaqueous solvents; i.e., the relative strengths of the bases were in the right order and spaced (DeltapK(a)). It was also observed that the strength of N-bases is highly dependent on the anion of the ionic liquid; this observation indicates that pH-dependent reactions could be controlled by the appropriate choice of anion for bulk ILs or as an added co-ion to bulk IL. PMID- 22050285 TI - Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain. AB - The induction of neuronal apoptosis throughout many regions of the developing rat brain by phenobarbital and phenytoin, two drugs commonly used for the treatment of neonatal seizures, has been well documented. However, several limbic regions have not been included in previous analyses. Because drug-induced damage to limbic brain regions in infancy could contribute to emotional and psychiatric sequelae, it is critical to determine the extent to which these regions are vulnerable to developmental neurotoxicity. To evaluate the impact of antiepileptic drug (AED) exposure on limbic nuclei, we treated postnatal day 7 rat pups with phenobarbital, phenytoin, carbamazepine, or vehicle, and examined nucleus accumbens, septum, amygdala, piriform cortex, and frontal cortex for cell death. Histologic sections were processed using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay to label apoptotic cells. Nucleus accumbens displayed the highest level of baseline cell death (vehicle group), as well as the greatest net increase in cell death following phenobarbital or phenytoin. Phenobarbital exposure resulted in a significant increase in cell death in all brain regions, whereas phenytoin exposure increased cell death only in the nucleus accumbens. Carbamazepine was without effect on cell death in any brain region analyzed, suggesting that the neurotoxicity observed is not an inherent feature of AED action. Our findings demonstrate pronounced cell death in several important regions of the rat limbic system following neonatal administration of phenobarbital, the first-line treatment for neonatal seizures in humans. These findings raise the possibility that AED exposure in infancy may contribute to adverse neuropsychiatric outcomes later in life. PMID- 22050287 TI - Address Abuse in Functional/Psychogenic Neurological Symptoms and Headache. PMID- 22050286 TI - Glucose metabolism in sporadic Creutzfeldt-Jakob disease: a statistical parametric mapping analysis of (18) F-FDG PET. AB - BACKGROUND AND PURPOSE: Reports describing functional neuroimaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), in sporadic Creutzfeldt-Jakob disease (sCJD) have consistently suggested that these tools are sensitive for the identification of areas of hypoperfusion or hypometabolism, even in the early stages of sCJD. However, there are few reports on the use of [18F]fluoro-2-deoxy-D-glucose (FDG) PET in sCJD, and most of them are single case reports. Only two small cohort studies based on visual inspection or a region of interest method have been published to date. Using a statistical parametric mapping (SPM) analysis of (18) F-FDG PET, we investigated whether there are brain regions preferentially affected in sCJD. METHODS: After controlling for age and gender, using SPM 2, we compared the glucose metabolism between (i) 11 patients with sCJD and 35 controls and (ii) the subset of five patients with the Heidenhain variant of sCJD and 35 controls. RESULTS: The patients with sCJD showed decreased glucose metabolism in bilateral parietal, frontal and occipital cortices. The Heidenhain variant of sCJD showed glucose hypometabolism mainly in bilateral occipital areas. CONCLUSIONS: Glucose hypometabolism in sCJD was detected in extensive cortical regions; however, it was not found in the basal ganglia or thalamus, which are frequently reported to be affected on diffusion-weighted images. The medial temporal area, which is possibly resistant to the prion deposits, was also less involved in sCJD. PMID- 22050288 TI - Highly enantioselective one-pot synthesis of spirocyclopentaneoxindoles containing the oxime group by organocatalyzed Michael addition/ISOC/fragmentation sequence. AB - A highly diastereo- and enantioselective organocatalytic protocol for the synthesis of biologically important spirocyclopentaneoxindoles containing the oxime functional group from easily accessible 3-allyl-substituted oxindoles and nitroolefins has been developed by a one-pot Michael addition/ISOC/fragmentation sequence. PMID- 22050289 TI - Systematic review and meta-analysis of the value of clinical features to exclude radiographic pneumonia in febrile neutropenic episodes in children and young people. AB - INTRODUCTION: Children and young people who present with febrile neutropenia (FNP) secondary to malignancies or their treatment frequently do not undergo routine chest radiography. With shorter courses of antibiotic therapy, failure to recognise pneumonia and consequent under-treatment could produce significant problems. METHODS: The review was conducted determine the value of the absence of clinical features of lower respiratory tract infection in excluding radiographic pneumonia at presentation of FNP using Centre for Reviews and Dissemination methods. It was registered with the HTA Registry of systematic reviews, CRD32009100453. Ten bibliographic databases, conference proceedings, reference lists and citations were searched. Cohort studies which compared clinical examination to radiographic findings were included. Results were summarised by random-effects meta-analysis. RESULTS: Four studies were included. Synthesis of the three higher-quality studies gave imprecise estimates of the average sensitivity (75%; 95% CI 52% to 89%) and average specificity (69%; 95% CI 57% to 78%) for clinical examination in the detection of radiographic pneumonia. If the prevalence of pneumonia is 5%, these estimates produce a negative predictive value of 98% (95% CI 96% to 99%). Alternatively, there remains a 1.9% probability of pneumonia (95% CI 0.7% to 4.2%). CONCLUSION: Signs and symptoms of lower respiratory infection have only moderate sensitivity and specificity for pneumonia; the low prevalence of the condition justifies the routine withholding of chest radiographs. However, for those with a predisposition to pneumonia, or re-presenting after a short course of antibiotic therapy, a chest X-ray should be performed despite an absence of signs. PMID- 22050290 TI - Non-classical HLA-E gene variability in Brazilians: a nearly invariable locus surrounded by the most variable genes in the human genome. AB - The non-classical human leukocyte antigen (HLA) class I genes present a very low rate of variation. So far, only 10 HLA-E alleles encoding three proteins have been described, but only two are frequently found in worldwide populations. Because of its historical background, Brazilians are very suitable for population genetic studies. Therefore, 104 bone marrow donors from Brazil were evaluated for HLA-E exons 1-4. Seven variation sites were found, including two known single nucleotide polymorphisms (SNPs) at positions +424 and +756 and five new SNPs at positions +170 (intron 1), +1294 (intron 3), +1625, +1645 and +1857 (exon 4). Haplotyping analysis did show eight haplotypes, three of them known as E*01:01:01, E*01:03:01 and E*01:03:02:01 and five HLA-E new alleles that carry the new variation sites. The HLA-E*01:01:01 allele was the predominant haplotype (62.50%), followed by E*01:03:02:01 (24.52%). Selective neutrality tests have disclosed an interesting pattern of selective pressures in which balancing selection is probably shaping allele frequency distributions at an SNP at exon 3 (codon 107), sequence diversity at exon 4 and the non-coding regions is facing significant purifying pressure. Even in an admixed population such as the Brazilian one, the HLA-E locus is very conserved, presenting few polymorphic SNPs in the coding region. PMID- 22050292 TI - Early alterations in left ventricular diastolic function in normotensive diabetic patients. AB - In diabetes mellitus, structural and functional alterations of the heart can be already present at the time of first diagnosis. However, how early these alterations may occur has never been fully clarified. The present study aimed at investigating cardiac functional abnormalities in uncomplicated hypertensive or normotensive patients with a recent diagnosis of diabetes mellitus. We studied 40 diabetics (24 normotensives and 16 hypertensives) by means of routine echocardiography plus pulse tissue Doppler analysis. Data were compared with those obtained in healthy age- and sex-matched controls. Left ventricular remodelling was more evident in hypertensive diabetics than in normotensive diabetics vs controls. Diastolic function was altered in diabetic patients only when detected by pulse tissue Doppler analysis and not by conventional transmitral Doppler evaluation. Normotensive patients with type 2 diabetes with little or no evidence at standard echocardiography of alterations in cardiac structure and function, already displayed an alteration in diastolic function when the evaluation was based on the tissue Doppler approach. Patients with type 2 diabetes combined to hypertension showed more evident functional cardiac alterations at echocardiography. These findings support the conclusion that cardiac abnormalities are very early phenomena in type 2 diabetes. PMID- 22050291 TI - Engineering pH-gated transitions for selective and efficient double-strand DNA photocleavage in hypoxic tumors. AB - We describe a family of hybrid compounds for the most efficient light-activated double-strand (ds) DNA cleavage known to date. This family represents the second generation of "switchable" molecular systems for pH-gated ds DNA-cleavage which combine a potent DNA-photocleaver and a pH-regulated part derived from a dipeptide. Design of the pH-switchable part utilizes amino groups of different basicity. Whereas the basic amino groups are protonated throughout the biologically relevant pH range, the pH-gating amines undergo protonation at the pH threshold which separates cancer and normal cells. Control over the reactivity and selectivity is achieved via transformation of the initial protonation state (a monocation or a dication) into a trication at the acidic pH. This change leads to an extraordinary increase in the efficiency of ds DNA cleavage leading to the ds:ss ratios comparable with the most efficient nonenzymatic ds DNA cleavers. Statistical analysis reveals that these high ds:ss ratios result from the combination of several factors: (a) true double-stranded cleavage, and (b) conversion of single-stranded (ss)-scission into ds cleavage. Considerable part of ds cleavage is also produced via the combination of ss cleavage events. PMID- 22050294 TI - The long-term effect of lockouts on alcohol-related emergency department attendances within Ballarat, Australia. AB - INTRODUCTION AND AIMS: Alcohol has consistently been demonstrated to increase levels of aggression and violence, particularly in late night licensed venues. Since August 2003, Ballarat (a regional city of approximately 95,000 inhabitants, in Victoria, Australia) has implemented a 3:00 AM 'lockout' with the goal of reducing alcohol-related harms. This paper is the first long-term analysis of the effect of this type of intervention on emergency department (ED) attendances. The aim of this paper is to examine the effectiveness of a lockout intervention within the city of Ballarat, Victoria on alcohol-related ED presentations. DESIGN AND METHODS: This paper examines alcohol-related injury frequencies pre- to post lockout intervention in Ballarat, Victoria, from 1999 to 2009, as indicated by ED International Classification of Diseases codes for acute alcohol intoxication and assault. These data are further compared with similar data from Geelong, Victoria, as a control. RESULTS: A small reduction in alcohol-related assaults and intoxication rates within Ballarat occurred before and after the introduction of the lockout. However, after this decline these rates steadily increased, surpassing Geelong by 2005. DISCUSSION AND CONCLUSIONS: There is no discernible long-term impact on alcohol-related ED attendances of the lockout intervention in Ballarat. As such, other interventions may be more appropriate to reduce alcohol related ED attendances. PMID- 22050293 TI - Donor-transmitted metastasis of colorectal carcinoma in a transplanted liver. AB - A 62-year-old man with alcoholic liver cirrhosis underwent liver transplantation. The transplantation went uneventful and the ultrasound imaging of the liver performed after transplantation did not show any abnormalities. Eighteen months later, an intra-hepatic focal lesion was found on ultrasound. A contrast-enhanced ultrasound revealed a lesion with a malignant pattern of contrast uptake. The histo-pathological and subsequent molecular-pathological analysis concluded a colorectal metastasis of donor origin. The donor had no history of malignancy but no complete autopsy had been performed which illustrates the importance of the meticulous donors' screening. Transplanted patients carry a high risk of developing malignancy in general but donor related-tumors are very rare. The therapeutic considerations differ substantially between recipient- and donor related malignancies. Therefore, considering the possibility of donor-related tumor by raising suspicion of malignant lesion with appropriate imaging and distinction from recipient-related malignancy by molecular analysis are crucial for proper therapeutic decision. PMID- 22050297 TI - International Guiding Principles for Biomedical Research Involving Animals issued by CIOMS. PMID- 22050296 TI - Editorial Publication of experimental animal research: Guiding Principles. PMID- 22050299 TI - Mental time travel after trauma: the specificity and temporal distribution of autobiographical memories and future-directed thoughts. AB - The present study investigated the relationship between trauma exposure and specificity and temporal distribution of autobiographical memories and future directed thoughts. A group of sexual assault victims were compared with women without previous trauma exposure in relation to specificity of autobiographical memories, as measured by the Autobiographical Memory Task (AMT) and specificity of future-directed thoughts as measured by the Future Cueing Task (FCT). The temporal distribution of future-directed thoughts and autobiographical memories was studied by asking the participants to estimate when each memory reported on the AMT had occurred and when each future event reported on the FCT would occur. The results showed no difference between the trauma group and the controls on specificity of autobiographical memories and future-directed thoughts. In line with a review of Moore and Zoellner (2007), PTSD symptoms as measured by the Impact of Event Scale (IES) correlated negatively with specificity. Furthermore, we observed no difference in temporal distribution of future-directed thoughts or autobiographical memories between trauma exposed participants and controls. PMID- 22050301 TI - Monovalent and mixed-valent potassium salts of [1,2,5]thiadiazolo[3,4 f][1,10]phenanthroline 1,1-dioxide: a radical anion for multidimensional network structures. AB - A novel phenanthlorine derivative, [1,2,5]thiadiazolo[3,4-f][1,10]phenanthroline 1,1-dioxide (tdapO(2)), was prepared to act as a radical-anion building block for coordination polymers. The crystal structures and magnetic properties of the monovalent and mixed-valent radical-anion salts K.tdapO(2) and K.(tdapO(2))(2) were elucidated and confirm the possibility of tdapO(2) to act as a bridging ligand and its capability to exhibit magnetic ordering at 15 K. PMID- 22050302 TI - Effect of detection methods on risk estimates of exposure to biosolids-associated human enteric viruses. AB - This study illustrates the effect of virus detection methods on estimates of risks of infection of biosolids-associated viruses for occupational workers and residential population during a hypothetical exposure of biosolids. Five gastroenteritis-associated human enteric viruses--enteroviruses (echovirus-12, enteroviruse types 68-71), adenoviruses, rotaviruses, and noroviruses genotype--I were considered to represent human enteric viruses for risk estimation purposes. Ingested viral doses were calculated using literature-reported total infectious virus concentrations (based on BGM and A549 cell lines) and genome copies (GCs) in Michigan dewatered and class B biosolids. Cell-line-based infectivity parameters (i.e., ratio of total infectious virus concentration to GCs) were developed for different viruses in biosolids to use GCs for calculating ingested viral dose, addressing the issue of integration of molecular methods with biosolids-based virus risk assessment. Use of virus concentrations from molecular methods (with and without using cell-line-based infectivity parameter) resulted in higher risk estimates than culture methods, indicating the effect of the virus detection method on risk estimates. Further, use of virus concentrations from A549 cell lines resulted in higher risk estimates compared to those from BGM cell lines, suggesting the need for a proper choice of cell lines in determining infectious viral dose. The Monte Carlo uncertainty analyses of estimates for risk of infection due to enteroviruses showed that enteroviruses concentration was the most important parameter influencing risk estimates, indicating the need for reducing associated uncertainty. More work is required to develop cell-line-based infectivity parameters for different virus concentration levels and sample matrix types using a cut-off-based approach. PMID- 22050305 TI - Organocatalytic, enantioselective intramolecular [6+2] cycloaddition reaction for the formation of tricyclopentanoids and insight on its mechanism from a computational study. AB - Diphenylprolinol silyl ether was found to be an effective organocatalyst for promoting the asymmetric, catalytic, intramolecular [6 + 2] cycloaddition reactions of fulvenes substituted at the exocyclic 6-position with a delta formylalkyl group to afford synthetically useful linear triquinane derivatives in good yields and excellent enantioselectivities. The cis-fused triquinane derivatives were obtained exclusively; the trans-fused isomers were not detected among the reaction products. The intramolecular [6 + 2] cycloaddition occurs between the fulvene functionality (6pi) and the enamine double bond (2pi) generated from the formyl group in the substrates and the diphenylprolinol silyl ether. The absolute configuration of the reaction products was determined by vibrational circular dichroism. The reaction mechanism was investigated using molecular orbital calculations, B3LYP and MP2 geometry optimizations, and subsequent single-point energy evaluations on model reaction sequences. These calculations revealed the following: (i) The intermolecular [6 + 2] cycloaddition of a fulvene and an enamine double bond proceeds in a stepwise mechanism via a zwitterionic intermediate. (ii) On the other hand, the intramolecular [6 + 2] cycloaddition leading to the cis-fused triquinane skeleton proceeds in a concerted mechanism via a highly asynchronous transition state. (iii) The fulvene functionality and the enamine double bond adopt the gauche-syn conformation during the C-C bond formation processes in the [6 + 2] cycloaddition. (iv) The energy profiles calculated for the intramolecular reaction explain the observed exclusive formation of the cis-fused triquinane derivatives in the [6 + 2] cycloaddition reactions. The reasons for the enantioselectivity seen in these [6 + 2] cycloaddition reactions are also discussed. PMID- 22050303 TI - Interaction of melittin peptides with perfluorocarbon nanoemulsion particles. AB - Melittin, an antimicrobial peptide, forms pores in biological membranes and triggers cell death. Therefore, it has potential as an anticancer therapy. However, until recently, the therapeutic application of melittin has been impractical because a suitable platform for delivery was not available. Recently, we showed that phospholipid-stabilized perfluorooctyl bromide based nanoemulsion particles (PFOB-NEPs) were resistant to destruction by melittin and enabled specific delivery of melittin to tumor cells, killing them and reducing tumor growth. Earlier, prior work also showed that melittin adsorbed onto the stabilizing phospholipid monolayer of PFOB-NEP but did not disrupt the phospholipid monolayer or produce "cracking" of the PFOB-NEPs. The present work identifies the important structural motifs for melittin binding to PFOB-NEPs through a series of atomistic molecular dynamics simulations. The conformational ensemble of melittin bound to PFOB-NEP lipid monolayer was compared to structure from a control simulation of melittin bound to a lipid bilayer to identify several differences in melittin-lipid interactions between the two systems. First, melittin was deeply buried in the hydrophobic tail region of bilayer, while its depth was attenuated in the PFOB-NEP monolayer. Second, a helical conformation was the major secondary structure in the bilayer, but the fraction of helix was reduced in the PFOB-NEP. Finally, the overall pattern for the direct interaction of melittin with surrounding lipids was similar between liposome and PFOB-NEP, but the level of interaction was slightly decreased in the PFOB-NEP. These results suggest that melittin interacts with the monolayer of PFOB-NEP in a way that is similar way to its interaction with bilayers but that deeper penetration into the hydrophobic interior is inhibited. PMID- 22050304 TI - The effectiveness of an improved multidisciplinary pain management programme: a 6 and 12-month follow-up study. AB - AIM: This article is a report of a Norwegian-revised study on the effectiveness of a follow-up multidisciplinary management programme for chronic pain to investigate the change processes associated with treatment. BACKGROUND: Substantial evidence supports the use of Cognitive Behavioural Therapy approaches to chronic pain. As relapse is often reported, follow-up sessions should be included. METHODS: A follow-up quasi-experimental design was performed, and a previous control group was used. The study initially included 117 participants, and 104 of the sample completed the 6- and 12-month follow-up programme. The 6 month follow-up consisted of therapeutic dialogue and education combined with physical activity. At the 12-month follow-up, a telephonic consultation was conducted. The data collection period was between September 2006 and January 2008. The statistical and clinical significance were considered. RESULTS: Findings suggest that this follow-up programme can potentially maintain the positive results of the basic programme in terms of reduced pain perception, improved health-related quality of life, and movement towards self-management. CONCLUSION: These results are consistent with the ultimate goal of Cognitive Behavioural Therapy approaches, which is to help patients with chronic pain to cope more effectively and to improve their health-related quality of life and functioning. To maintain treatment improvements and advance nursing, there is a clear need for research that tests the efficacy of follow-up interventions that are designed to prevent drop out and relapse. PMID- 22050306 TI - Outcomes of ovarian stimulation in a two-day oocyte collection week with PGD cycles compared to a five-day oocyte collection week with conventional IVF/ICSI cycles. AB - We assessed the outcomes of ovarian stimulation in a two-day egg collection (EC) week with preimplantation genetic diagnosis (PGD) cycles (N = 307) compared to a five-day EC week with conventional in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles (N = 2,417). The mean (SD) age of women undergoing PGD was 34 (3.97) and 35 (3.85) for IVF/ICSI (P < 0.001), the number of oocytes collected was 13 (7.37) and 11 (7.02), (P < 0.001), while the mean (SD) number of fertilized oocytes was 8 (5.09) and 6 (4.58), respectively (P < 0.001). The clinical pregnancy rate per embryo transfer (ET) was 37% with PGD and 38% with IVF/ICSI (P = 0.49), while the implantation rate was 0.35 and 0.30, respectively (P = 0.05). After adjusting for age and confounding variables including the number of oocytes collected and fertilized normally, the mode of treatment (PGD or IVF/ICSI) had no effect on clinical pregnancy (P = 0.48). In conclusion, scheduling of PGD cycles to a two-day EC week did not compromise the outcomes of ovarian stimulation when compared to a five-day EC week with conventional IVF/ICSI cycles. This can allow the provision of a more patient friendly service, increase the flexibility of satellite PGD services, and facilitate cycle programming with the genetics team providing PGD. PMID- 22050307 TI - Anti-IL-33 antibody has a therapeutic effect in a murine model of allergic rhinitis. AB - BACKGROUND: Interleukin (IL)-33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti-IL-33 for allergic rhinitis (AR). METHODS: Twenty four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B [ovalbumin (OVA) group, n = 6] mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti-IL-33 group, n = 6), anti-IL-33 was injected before challenge. We evaluated the number of nose-scratching events and external morphology; serum total and OVA-specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL-4, IL-5, and IL-13 in BAL fluid. RESULTS: Anti-IL-33 treatment significantly reduced the nose-scratching events and ameliorated skin denudation. Serum total and OVA-specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after treatment. CONCLUSIONS: Anti-IL-33 antibody has a therapeutic potential for experimental AR. PMID- 22050308 TI - Computational tests of models for kinetic parameters of unimolecular reactions of organophosphorus and organosulfur compounds. AB - A computational study of the kinetics of isomerization and elimination reactions of organophosphorus and organosulfur reactions is presented with a view to characterizing the predictive capabilities of widely applied techniques for processes that pertain to the destruction of chemical warfare agents. A set of 22 reactions has been studied, and the results have been compared to experimentally derived data. The BMK functional and the MG3S basis set have been used to compute minimum energy paths. Corrections have been added from CBS-QB3, CASSCF, and CASMP2 calculations. Thermal rate constants at experimental temperatures have been calculated with canonical variational transition state theory and small curvature tunneling theory. The quality of these results may depend on recrossing of the variational transition state, the amount of radical or diradical character found in the minimum energy paths, or the accuracy of barrier heights. PMID- 22050309 TI - The therapeutic potential of the adiponectin pathway. AB - Adiponectin is an adipocyte-derived hormone that has been shown to play an important role in the regulation of metabolic, inflammatory, and apoptotic pathways. Adiponectin improves insulin sensitivity, promotes vascular health, and increases cell survival. These observations suggest a potential therapeutic role for adiponectin in the treatment of diabetes mellitus, cardiovascular diseases, and cancer. However, biologically active recombinant adiponectin proteins are inherently unstable and difficult to produce, thus making it a challenge for both research and clinical development. One main challenge relates to the existence of adiponectin as homo-/hetero-trimers, and complexes containing multiple adiponectin trimer units, in plasma. The underlying mechanism for adiponectin function is also not completely understood. Two receptors for adiponectin (ADIPOR1 and ADIPOR2) have been cloned, and activation of adenosine monophosphate activated kinase (AMPK) has been reported to be downstream of the receptors. Recent findings suggest that adiponectin potently stimulates ceramidase activity via activation of its two known receptors, therefore connecting sphingolipid metabolism to adiponectin functions and providing a potential mechanism explaining the different actions of adiponectin. Interestingly, a new report also identified a pathway involving adiponectin and insulin receptor substrate 2, which is independent of the ADIPOR1/ADIPOR2 pathway. In this manuscript, we will review previous approaches and challenges in exploring adiponectin-based therapeutics. In particular, we will review some of the recent developments in engineering adiponectin proteins as well as potential therapeutic opportunities offered by recently elucidated adiponectin-mediated signaling pathways. PMID- 22050310 TI - How can we enhance girls' interest in scientific topics? AB - BACKGROUND: Girls are considerably less interested in scientific subjects than boys. One reason may be that scientific subjects are considered to be genuinely masculine. Thus, being interested in science may threaten the self-perception of girls as well as the femininity of their self-image. AIMS: If scientific topics that are considered to be stereotypically feminine were chosen, however, this potential threat might be overcome which, in turn, might lead to an increase in girls' interest in science. This hypothesis was empirically tested by means of two studies. SAMPLE: Participants were 294 (Study 1) and 190 (Study 2) Grade 8 to Grade 9 students. METHOD: Gender differences in students' interest in masculine and feminine topics were investigated for a range of scientific concepts (Study 1) as well as for a given scientific concept (Study 2) for four scientific subjects (i.e., biology, physics, information technology, and statistics), respectively. RESULTS: Both studies indicated that the mean level of girls' scientific interest was higher when scientific concepts were presented in the context of feminine topics and boys' level of scientific interests was higher when scientific concepts were presented in the context of masculine topics. CONCLUSION: Girls' interest in science could be substantially increased by presenting scientific concepts in the context of feminine topics. Gender differences as well as individual differences in the level of interest in scientific topics may be taken into account by creating learning environments in which students could select the context in which a certain scientific concept is embedded. PMID- 22050311 TI - Pedagogical strategies for teaching literacy to ESL immigrant students: a meta analysis. AB - BACKGROUND: Many countries rely on immigrants for population growth and to maintain a skilled workforce. However, many such immigrants face literacy-related barriers to success in education and in the labour force. AIMS: This meta analysis reviews experimental and quasi-experimental studies to examine strategies for teaching English literacy to immigrant students. METHOD: Following an exhaustive and systematic search for studies meeting pre-determined inclusion criteria, two researchers independently extracted data from 26 English as a Second Language (ESL) studies involving 3,150 participants. These participants consisted of ESL immigrant students in kindergarten through grade 6 who were exposed to English literacy instructional interventions. Measured outcomes were reading and writing. RESULTS AND CONCLUSIONS: Mean effect sizes vary from small to large, depending on instructional interventions and outcome constructs. Across several different grade levels, settings, and methodological features, pedagogical strategies used in teaching ESL to immigrant students are associated with increased competence in reading and writing. Collaborative reading interventions, in which peers engage in oral interaction and cooperatively negotiate meaning and a shared understanding of texts, produced larger effects than systematic phonics instruction and multimedia-assisted reading interventions. The results show that the pedagogical strategies examined in this meta-analysis produced statistically significant benefits for students in all grade levels. The findings also show that students from low socio-economic status (SES) background benefit from ESL literacy interventions. However, significant heterogeneity was found in each subset. Educators and policy makers are encouraged to consider specific school contexts when making decisions about optimal pedagogical strategies. It is possible that contextual factors as well as ESL learner characteristics may influence the effectiveness of these strategies. To ensure literacy acquisition for immigrant students whose primary language is not English, it is important to continue to research successful literacy practices in ways that better inform educators and policy makers. PMID- 22050312 TI - The influences of course effort, mastery and performance goals, grade expectancies, and earned course grades on student ratings of course satisfaction. AB - BACKGROUND: The positive relation between course grades and student ratings of course satisfaction is well established but controversy continues concerning the magnitude, interpretation, and implications of this association. AIMS: This study examined the within course relations of a set of variables often implicated as potential contributors to the grade-student rating relation. SAMPLE: Two-hundred and twenty students enrolled in an internet-based university course. METHOD: Measures of course mastery and performance goals, expected grades, course effort, cumulative GPA, and final course grade were prospectively collected. The dependent variable was a global measure of course satisfaction obtained at the end of the semester. RESULTS: A path model fit the data very well and all study variables directly or indirectly predicted course satisfaction. Grades had a moderately strong effect, half of which was independent of other model variables. Adjusting for all model variables, students high on mastery course goals evaluated the course more positively whereas students high on performance goals provided less favourable evaluations. CONCLUSIONS: Students can assess the same course and instructor in different ways depending upon such factors as their degree of success, their motivations for taking the course, and the amount of effort invested. Course satisfaction, then, can be substantially influenced by factors loosely or unrelated to course or teacher effectiveness. PMID- 22050313 TI - Performance-approach and performance-avoidance classroom goals and the adoption of personal achievement goals. AB - BACKGROUND: Students' perceptions of classroom goals influence their adoption of personal goals. To assess different forms of classroom goals, recent studies have favoured an overall measure of performance classroom goals, compared to a two dimensional assessment of performance-approach and performance-avoidance classroom goals (PAVCG). AIMS: This paper considered the relationship between students' perceptions of classroom goals and their endorsement of personal achievement goals. We proposed that three (instead of only two) classroom goals need to be distinguished. We aimed to provide evidence for this hypothesis by confirmatory factor analysis (CFA) and also by divergent associations between the respective classroom goal and students' personal goal endorsement. SAMPLE: A total of 871 (474 female) 10th grade students from several German high schools participated in this study. METHOD: Students responded to items assessing their perception of mastery, performance-approach, and performance-avoidance goals in the classroom. Additionally, the students reported how much they personally pursue mastery, performance-approach, and performance-avoidance goals. All items referred to German as a specific school subject. RESULTS.A CFA yielded empirical support for the proposed distinction of three (instead of only two) different kinds of classroom goals. Moreover, in hierarchical linear modelling (HLM) analyses all three classroom goals showed unique associations with students' personal goal adoption. CONCLUSIONS: The findings emphasized the need to distinguish performance-approach and PAVCG. Furthermore, our results suggest that multiple classroom goals have interactive effects on students' personal achievement strivings. PMID- 22050314 TI - Subtypes of medial temporal lobe epilepsy: influence on temporal lobectomy outcomes? AB - Surgical resection of the hippocampus is the most successful treatment for medication-refractory medial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis. Unfortunately, at least one of four operated patients continue to have disabling seizures after surgery, and there is no existing method to predict individual surgical outcome. Prior to surgery, patients who become seizure free appear identical to those who continue to have seizures after surgery. Interestingly, newly converging presurgical data from magnetic resonance imaging (MRI) and intracranial electroencephalography (EEG) suggest that the entorhinal and perirhinal cortices may play an important role in seizure generation. These areas are not consistently resected with surgery and it is possible that they continue to generate seizures after surgery in some patients. Therefore, subtypes of MTLE patients can be considered according to the degree of extrahippocampal damage and epileptogenicity of the medial temporal cortex. The identification of these subtypes has the potential to drastically improve surgical results via optimized presurgical planning. In this review, we discuss the current data that suggests neural network damage in MTLE, focusing on the medial temporal cortex. We explore how this evidence may be applied to presurgical planning and suggest approaches for future investigation. PMID- 22050315 TI - Diabetes and previous stroke: hazards for intravenous thrombolysis? AB - BACKGROUND AND PURPOSE: Alteplase licensing approval in Europe does not advocate intravenous thrombolysis (IVT) for diabetic ischaemic stroke (IS) patients with previous cerebral infarction (PCI). Our aim was to assess whether concomitant diabetes mellitus (DM) and PCI are associated with symptomatic intracerebral haemorrhage (SICH) and poor outcome after IVT. METHODS: Multicentre prospective registry, which included consecutive IVT-treated, acute IS patients from January 2003 to December 2010. The frequency of SICH (SITS-MOST criteria) and 3-month outcomes (mRS) were compared between the following groups: (i) diabetic patients with PCI (DM+/PCI+); (ii) diabetic patients without PCI (DM+/PCI-); (iii) non diabetic patients with PCI (DM-/PCI+); and (iv) patients without diabetes or PCI (DM-/PCI-). RESULTS: A total of 1475 patients were included. Thirty-four patients (2.3%) had known DM and PCI, 258 (17.5%) were diabetics without PCI, and 119 (8.1%) had a PCI and no DM. Thirty-six patients (2.6%) developed SICH, with no differences between groups (P = 985). Fifteen (40.9%) DM+/PCI+ patients, 113 (46.5%) DM+/PCI- patients, 47 (42%) DM-/PCI+ patients and 414 (40.9%) DM-/PCI- patients had mRS >= 3 at 3 months (P = 427). The presence neither of DM nor of PCI, nor their combination, had any impact on the risk of SICH or on outcome at 3 months after adjusting for age, stroke severity and glucose levels on admission. CONCLUSIONS: Acute IS diabetic patients with PCI who were treated with IVT had similar outcomes to patients without such history, with no increase in the rates of SICH. Thus, they should not be excluded from IVT only on the basis of DM and PCI. PMID- 22050316 TI - Dravet syndrome--considerable delay in making the diagnosis. AB - OBJECTIVES: To assess delay in diagnosis and clinical characteristics of Dravet syndrome based on the Dravet register at The National Centre for Epilepsy in Norway. MATERIAL AND METHODS: Medical records of patients diagnosed with Dravet syndrome since 2007 were analysed. RESULTS: Twenty-two patients were identified. In 15, genetic screening disclosed mutations/deletions in the SCN1A gene. Average time from seizure onset to diagnosis was 7.4 years. Mean age at seizure onset was 6.7 months, nine had hemiconvulsions and 13 had generalized tonic-clonic seizures. The seizures were precipitated by fever in 17, by external heating in three. During second year of life, multiple seizure types and cognitive and motoric stagnation occurred. No patients became seizure-free with antiepileptic drugs. The effect of vagal nerve stimulation was disappointing. CONCLUSIONS: By making an early diagnosis, an extensive presurgical evaluation may be avoided, and the patient and their parents may be offered genetic guidance. PMID- 22050317 TI - Migraine attack frequency, duration, and pain intensity: disease burden derived from a community-based survey in northern Tanzania. AB - OBJECTIVE: One goal of the campaign "Lifting the burden: The global campaign against headache" is to highlight existing evidence about headache worldwide. In this context, the aim of our study was to report the migraine-related headache burden in northern Tanzania. METHODS: From December 2003 until June 2004 a community-based door-to-door survey was undertaken in northern Tanzania, using multistage cluster sampling. Based on the criteria of the International Headache Society, 7412 individuals were enrolled in this survey. RESULTS: Migraine patients' average annual attack frequency was 18.4 (n = 308, standard deviation [SD] +/- 47.4) with a mean duration of 16.4 hours (SD +/- 20.6). The average headache intensity per patient was 2.65 (SD +/- 0.59) with a calculated loss of 6.59 (SD +/- 26.7) working days per year. Extrapolation of data to the investigated population (n = 7412) resulted in annual migraine burden of 281.0 migraine days per 1000 inhabitants. CONCLUSIONS: To our knowledge, this study reports for the first time the burden that arises from migraine headache in a rural population of sub-Sahara Africa (SSA). As the presented migraine-related burden is considerable, we hope that our data will increase the awareness among local decision makers in allocating resources for treatment and research on headache. PMID- 22050318 TI - Alkylated flavanones from the bark of Cryptocarya chartacea as dengue virus NS5 polymerase inhibitors. AB - An in vitro screening of New Caledonian plants allowed the selection of several species with a significant dengue virus NS5 RNA-dependent RNA polymerase (RdRp) inhibiting activity. The chemical investigation of Cryptocarya chartacea led to the isolation of a series of new mono- and dialkylated flavanones named chartaceones A-F (1-6), along with pinocembrin. They were isolated as racemic mixtures and characterized using extensive one- and two-dimensional NMR spectroscopy. Four diastereomers of chartaceone A (1) were separated using chiral HPLC, and their absolute configurations were established by comparison of their experimental and calculated ECD spectra. The dialkylated flavanones, chartaceones C-F (3-6), exhibited the most significant NS5 RdRp inhibiting activity, with IC(50) ranging from 1.8 to 4.2 MUM. Chartaceones represent a new class of non nucleosidic inhibitors of the DENV NS5 RdRp. PMID- 22050319 TI - 'Hotspots' for aggression in licensed drinking venues. AB - INTRODUCTION AND AIMS: In order to better understand the social context of barroom aggression, the aim was to identify common locations ('hotspots') for aggression in bars and examine the association of hotspots with aggression severity and environmental characteristics. DESIGN AND METHODS: Aggression hotspots were identified using narrative descriptions and data recorded on premises' floor plans for 1057 incidents of aggression collected in the Safer Bars evaluation. Hierarchical Linear Modelling was used to identify bar-level and night-level characteristics associated with each hotspot. RESULTS: The most common location for aggression was the dance floor (20.0% of incidents) or near the dance floor (11.5%), followed by near the serving bar (15.7%), at tables (13.1%), aisles, hallways and other areas of movement (6.2%), entrance (4.5%) and the pool playing area (4.1%). Hotspots were predicted mainly by bar-level characteristics, with dance floor aggression associated with crowded bars, a high proportion of female and young patrons, lots of sexual activity, a large number of patrons and staff, security staff present, better monitoring and coordination by staff, and people hanging around at closing. Incidents at tables and pool tables tended to occur in bars with the opposite characteristics. Nightly variations in patron intoxication and rowdiness were associated with aggression at tables while variations in crowding and sexual activity were associated with aggression in areas of movement. Incidents outside tended to be more severe. DISCUSSION AND CONCLUSIONS: Each aggression location and their associated environments have somewhat different implications for staff training, premises design, policy and prevention. PMID- 22050321 TI - NF-Y and the transcriptional activation of CCAAT promoters. AB - The CCAAT box promoter element and NF-Y, the transcription factor (TF) that binds to it, were among the first cis-elements and trans-acting factors identified; their interplay is required for transcriptional activation of a sizeable number of eukaryotic genes. NF-Y consists of three evolutionarily conserved subunits: a dimer of NF-YB and NF-YC which closely resembles a histone, and the "innovative" NF-YA. In this review, we will provide an update on the functional and biological features that make NF-Y a fundamental link between chromatin and transcription. The last 25 years have witnessed a spectacular increase in our knowledge of how genes are regulated: from the identification of cis-acting sequences in promoters and enhancers, and the biochemical characterization of the corresponding TFs, to the merging of chromatin studies with the investigation of enzymatic machines that regulate epigenetic states. Originally identified and studied in yeast and mammals, NF-Y - also termed CBF and CP1 - is composed of three subunits, NF-YA, NF-YB and NF-YC. The complex recognizes the CCAAT pentanucleotide and specific flanking nucleotides with high specificity (Dorn et al., 1997; Hatamochi et al., 1988; Hooft van Huijsduijnen et al, 1987; Kim & Sheffery, 1990). A compelling set of bioinformatics studies clarified that the NF-Y preferred binding site is one of the most frequent promoter elements (Suzuki et al., 2001, 2004; Elkon et al., 2003; Marino-Ramirez et al., 2004; FitzGerald et al., 2004; Linhart et al., 2005; Zhu et al., 2005; Lee et al., 2007; Abnizova et al., 2007; Grskovic et al., 2007; Halperin et al., 2009; Hakkinen et al., 2011). The same consensus, as determined by mutagenesis and SELEX studies (Bi et al., 1997), was also retrieved in ChIP-on chip analysis (Testa et al., 2005; Ceribelli et al., 2006; Ceribelli et al., 2008; Reed et al., 2008). Additional structural features of the CCAAT box - position, orientation, presence of multiple Transcriptional Start Sites - were previously reviewed (Dolfini et al., 2009) and will not be considered in detail here. PMID- 22050322 TI - Long-term neurocognitive and neuroimaging outcomes in posterior reversible encephalopathy syndrome: two case reports and implications. AB - Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic and neurometabolic state associated with a distinct appearance on computed tomography and magnetic resonance imaging, as well as particular clinical features. While PRES is defined as a reversible condition, instances of irreversible or persisting cytotoxic edema have been reported and appear to be associated with poor outcomes. Studies addressing the post-acute neurocognitive findings in persisting/irreversible PRES are lacking. We report two cases of persisting PRES with associated neurocognitive deficits and functional limitations following acute presentation. Neuroimaging revealed abnormalities within the posterior parietal lobes, along with bilateral involvement of the occipital and frontal lobes. The results from the neuropsychological examination revealed a pattern of impairment generally affecting spatial-perceptual and related functions and aspects of executive function. These cases document instances of irreversible/persisting PRES with associated neurocognitive deficits and functional limitations generally corresponding with the areas implicated on neuroimaging. Studies addressing the post-acute neurocognitive presentation and functional outcomes of PRES are needed. PMID- 22050323 TI - Mechanistic studies of the effect of bile salts on rhodamine 123 uptake into RBE4 cells. AB - To examine the ability of bile salts (BS) to act as permeation enhancers at the blood brain barrier, the effect of four BS (cholate, deoxycholate, monoketocholate and taurocholate) on accumulation of rhodamine 123 (R123) in rat brain endothelial (RBE4) cells was investigated. Experiments were performed using BS concentrations shown to be noncytotoxic to RBE4 cells. Uptake and efflux of R123 in the absence and presence of BS were studied by fluorescence spectroscopy and confocal microscopy. Changes in RBE4 cell membrane fluidity in the presence of BS were evaluated using fluorescence anisotropy. The direct interaction between BS and R123 (ion pairing) and the effect of BS on distribution of R123 into liposomes were studied by capillary electrophoresis. All BS influenced R123 uptake in a concentration-dependent manner and increased cell membrane fluidity. Monoketocholate produced the greatest increase in uptake and also significantly reduced R123 efflux probably by inhibition of P-glycoprotein (P-gp). Direct interaction of BS and R123 was weak, but distribution of R123 into liposomes was increased by BS. The results suggest that BS increase R123 uptake by increasing cell membrane fluidity and, in the case of MKC, by inhibiting P-gp. PMID- 22050324 TI - A new organotypic model containing dermal-type macrophages. AB - Human skin equivalents (SEs) are popular three-dimensional (D) cell culture systems in fundamental and applied dermatology. They have been made to contain dendritic cells, but so far no study on the incorporation of potentially anti inflammatory dermal macrophages has been performed. Here, we show that monocyte derived dermal-type macrophages can be introduced into a rigid scaffold with dermal fibroblasts. They maintain their cell surface markers CD163, DC-SIGN/CD209 and HLA-DR, which discriminate them from monocytes and dendritic cells. They retain the ability to produce the anti-inflammatory cytokine IL-10 in response to lipopolysaccharide (LPS) and to phagocytose latex beads. We thus demonstrate the feasibility of creating macrophage-fibroblast 3D cultures as a first step towards generating SEs with dermal macrophages. PMID- 22050325 TI - Public perceptions of hurricane modification. AB - If hurricane modification were to become a feasible strategy for potentially reducing hurricane damages, it would likely generate public discourse about whether to support its implementation. To facilitate an informed and constructive discourse, policymakers need to understand how people perceive hurricane modification. Here, we examine Florida residents' perceptions of hurricane modification techniques that aim to alter path and wind speed. Following the mental models approach, we conducted a survey study about public perceptions of hurricane modification that was guided by formative interviews on the topic. We report a set of four primary findings. First, hurricane modification was perceived as a relatively ineffective strategy for damage reduction, compared to other strategies for damage reduction. Second, hurricane modification was expected to lead to changes in projected hurricane path, but not necessarily to the successful reduction of projected hurricane strength. Third, more anger was evoked when a hurricane was described as having changed from the initially forecasted path or strength after an attempted modification. Fourth, unlike what we expected, participants who more strongly agreed with statements that recognized the uncertainty inherent in forecasts reported more rather than less anger at scientists across hurricane modification scenarios. If the efficacy of intensity-reduction techniques can be increased, people may be willing to support hurricane modification. However, such an effort would need to be combined with open and honest communications to members of the general public. PMID- 22050326 TI - Development of semen quality following reversible downregulation of testicular function in male dogs with a GnRH agonist implant. AB - Slow-release GnRH agonist implants have shown to be an effective and reversible alternative to surgical castration. Testicular function is downregulated with an arrest of spermatogenesis on the level of spermatogonia/primary spermatocytes but is fully restored after abolition of downregulation. Aim of this study was to assess the quality of ejaculates after active abolishment of downregulation by implant removal and to follow recrudescence of spermatogenesis. Five dogs - which served as their own controls - were treated with a slow-release implant containing the GnRH agonist azagly-nafarelin. Implants were removed during full downregulation (testosterone <0.1 ng/ml), and attempts to collect ejaculates started from week 4 onwards to week 29. First ejaculates could be obtained between weeks 8 and 12 with the first fully elongated spermatozoa observed in week 10. Volume, %motility and total sperm count increased and %pathomorphology decreased during the course of the study with all ejaculates being in the normal range by week 29. Our data indicate that onset of recrudescence of spermatogenesis coincides with the first testosterone increase after active abolishment of downregulation. Semen quality was fully regained with a significant improvement of %pathomorphology (p < 0.05) and a tendency of improved %motility. However, these observations on an improved semen quality need further validation and no final conclusions can be drawn yet. PMID- 22050327 TI - Risk and protective factors associated with postnatal depression in Mexican adolescents. AB - We explored factors associated with postnatal depression and further evaluated whether any of these risk and protective factors are specific for adolescent mothers. Data concerning depression levels, family and individual factors were collected in a cross-sectional study which surveyed 298 women in Monterrey, N.L., Mexico. Mean maternal age was 24.64 years, and 27.18% of the mothers were between 14 and 19 years old. Prevalence of postnatal depression was higher in adolescents (16.05%) than in adult mothers (14.29%) but, on average, this difference was not significant. The association between individual factors and postnatal depression for both adult and adolescent mothers was explored. Our results revealed that social support is significantly associated with less possibility of postnatal depression in both groups, and that this effect is stronger for adolescents (OR=0.81) than for adults (OR=0.92). For the sample as a whole postnatal depression was associated with lower levels of education, reported fear during labor and living with partner. We also found that having a girl greatly increased the possibility of postnatal depression. We conclude that social support is a protective factor associated with postnatal depression, especially for adolescents. PMID- 22050328 TI - Comparison between tissue doppler imaging (TDI) and tissue synchronization imaging (TSI) in evaluation of left ventricular dyssynchrony in patients with advanced heart failure. AB - BACKGROUND: Assessment of left ventricular (LV) dyssynchrony has an important role in optimizing the selection of cardiac resynchronization therapy (CRT) candidates. We compared a new semiautomatic echocardiographic modality, tissue synchronization imaging (TSI) with a manual method, color-coded tissue Doppler imaging (TDI), in the assessment of LV dyssynchrony in patients with heart failure (HF). METHODS: Ninety-five patients (age = 54.5 +/- 17.1 years, 66.3% male) with advanced HF (NYHA functional class >=III and ejection-fraction <=35%) were included in the study and evaluated echocardiographically. The time to regional peak systolic velocity (Ts) in six basal and six middle segments of the LV was measured manually using velocity curves from TDI and semiautomatically using TSI and seven parameters of systolic dyssynchrony were computed. RESULTS: Overall, a moderate-to-good association was found between Ts derived by these two modalities, whereas the mean of Ts via TSI was significantly lower than that measured by TDI in many LV segments. The agreement between these two modalities in identifying LV dyssynchrony varied from weak to moderate according to various dyssynchrony indices. In comparison to the TDI-derived dyssynchrony indices, TSI showed a high sensitivity of more than 90% using Ts delay at the basal/all LV segments and the indices for their standard deviations (SD) for identifying LV dyssynchrony, whereas the highest specificity of 80% was achieved using the septal-lateral dyssynchrony index in the prediction of LV dyssynchrony. CONCLUSION: With the aid of selected LV dyssynchrony indices, the TSI method may confer enough sensitivity for a speedy evaluation and initial screening of LV dyssynchrony in HF patients; however, the current technology of TSI does not seem specific enough to replace TDI in the evaluation of dyssynchrony. PMID- 22050329 TI - Deciphering the DNAzyme activity of multimeric quadruplexes: insights into their actual role in the telomerase activity evaluation assay. AB - The end of human telomeres is comprised of a long G-rich single-stranded DNA (known as 3'-overhang) able to adopt an unusual three-dimensional "beads-on-the string" organization made of consecutively stacked G-quadruplex units (so-called quadruplex multimers). It has been widely demonstrated that, upon interaction with hemin, discrete quadruplexes acquire peroxidase-mimicking properties, oxidizing several organic probes in H(2)O(2)-rich conditions; this property, known as DNAzyme, has found tens of applications in the last two decades. However, little is known about the DNAzyme activity of multimeric quadruplexes; this is an important question to address, especially in light of recent reports that exploit the DNAzyme process to optically assess the activity of an enzyme that elongates the telomeric overhang, the telomerase. Herein, we thoroughly investigate the DNAzyme activity of long telomeric fragments, with a particular focus on both the nature of the hemin/multimeric quadruplex interactions and the putative higher-order fold of the studied fragments; in light of our results, we also propose possible ways that may be followed to improve the use of DNAzyme to evaluate the telomerase activity. PMID- 22050330 TI - 'Therapeutic emplotment': a new paradigm to explore the interaction between nurses and patients with a long-term illness. AB - AIMS: This paper presents a discussion of the use of 'therapeutic emplotment' during health professional-patient interactions when caring for patients with a long-term illness, with implications for nursing. BACKGROUND: Therapeutic emplotment' develops from two philosophical strains: one emphasizing the connection of speech to actions, the other the linguistically mediated nature of human experience. Mattingly defines therapeutic emplotment as the creation of story-like structures through therapist-patient interactions which encourage the patient to see therapy as integral to healing. DATA SOURCES: A literature search for the period 1994-2010 was undertaken using the keywords therapeutic emplotment, chronic illness, illness narratives, nursing narratives and nurse patient interaction in the following databases: CINAHL, MEDLINE, COCHRANE, Social Care online, PsycInfo and AnthroSource. Reference lists of papers and books were examined for relevant studies published before 1994. DISCUSSION: Differing from other social scientists, Mattingly highlights potential of narratives to create experiences in clinical practice. With therapeutic emplotment, narratives become 'tools' in the hands of health professionals to shape the interaction with patients with a long-term illness and are constructed by them together. This introduces changes in the way health professionals, including nurses, look at their practice. IMPLICATIONS FOR NURSING: Therapeutic emplotment may provide nurses with a way of improving communication and relationship skills to help patients reach therapeutic goals; its use may also help qualitative research that explores the impact of nurses' interactions with patients on the quality of care. CONCLUSION: Therapeutic emplotment may be used by a broader range of health professionals, including nurses, for clinical and research purposes. PMID- 22050331 TI - Insight into the photoinduced ligand exchange reaction pathway of cis-[Rh2(MU O2CCH3)2(CH3CN)6]2+ with a DNA model chelate. AB - We previously showed that [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) binds to dsDNA only upon irradiation with visible light and that photolysis results in a 34-fold enhancement of its cytotoxicity toward Hs-27 human skin fibroblasts, making it potentially useful for photodynamic therapy (PDT). With the goal of gaining further insight on the photoinduced binding of DNA to the complex, we investigated by NMR spectroscopy the mechanism by which 2,2'-bipyridine (bpy), a model for biologically relevant bidentate nitrogen donor ligands, binds to [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) upon irradiation in D(2)O. The photochemical results are compared to the reactivity in the dark in D(2)O and CD(3)CN. The photolysis of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) with equimolar bpy solutions in D(2)O with visible light affords [Rh(2)(O(2)CCH(3))(2)(eq/eq bpy)(CH(3)CN)(2)(D(2)O(ax))(2)](2+) (eq/eq) with the reaction reaching completion in ~8 h. Only vestiges of eq/eq are observed at the same time in the dark, however, and the reaction is ~20 times slower. Conversely, the dark reaction of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) with an equimolar amount of bpy in CD(3)CN affords [Rh(2)(O(2)CCH(3))(2)(eta(1)-bpy(ax))(CH(3)CN)(5)](2+) (eta(1)-bpy(ax)), which remains present even after 5 days of reaction. The photolysis results in D(2)O are consistent with the exchange of one equiv CH(3)CNeq for solvent, and the resulting species quickly reacting with bpy to generate eq/eq; the initial eq ligand dissociation is assisted by absorption of a photon, thus greatly enhancing the reaction rate. The photolytic reaction of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+):bpy in a 1:2 ratio in D(2)O affords the eq/eq and (eq/eq)(2) adducts. The observed differences in the reactivity in D(2)O vs CD(3)CN are explained by the relative ease of substitution of eq D(2)O vs CD(3)CN by the incoming bpy molecule. These results clearly highlight the importance of dissociation of an eq CH(3)CN molecule from the dirhodium core to attain high reactivity and underscore the importance of light for the reactivity of these compounds, which is essential for PDT agents. PMID- 22050332 TI - Overcoming food allergy through acquired tolerance conferred by transfer of Tregs in a murine model. AB - BACKGROUND: The number of food allergy patients is increasing. Some children outgrow their food allergies through tolerance, whereas others remain susceptible throughout their lives. We aimed to contribute to food allergy therapeutics by understanding induction of oral tolerance in a murine food allergy model. METHODS: We modified an existing murine food allergy model by using ovalbumin (OVA) to induce oral tolerance, either by pretreating mice with OVA or by transferring mesenteric lymph node (MLN) cells or T cells derived from mice treated with OVA. RESULTS: Pretreatment with OVA prevented food allergy, with complete suppression of OVA-specific immunoglobulin (Ig)E and IgA antibody production and interleukin (IL)-4, IL-10, and IL-9 mRNA expression. The proportion of regulatory T cells (Tregs) in MLN cells and expression of transforming growth factor-beta mRNA increased. In the transfer model, anaphylaxis secondary to OVA intake was suppressed by transfer of whole MLN cells and Tregs from OVA-treated mice. However, OVA-specific IgE and IgA expressions were partially attenuated by transfer of antigen-specific and nonspecific Tregs, but not by whole MLN cells from OVA-treated mice. In the Treg transfer model, IL 4 and IL-10 mRNA expression decreased, but IL-9 mRNA expression increased. CONCLUSION: We concluded that oral tolerance for food antigens is induced in two ways: (i) by initial exposure to antigen, or inherent tolerance, and (ii) by transfer of Tregs, or acquired tolerance. Because food allergies occur when inherent tolerance is absent, understanding of acquired tolerance is important for the development of therapies for food allergy. PMID- 22050333 TI - Exponential sensitivity and speciation of Al(III), Sc(III), Y(III), La(III), and Gd(III) at fused silica/water interfaces. AB - The binding contants, adsorption free energies, absolute adsorbate number densities, and interfacial charge densities of Al(III), Sc(III), Y(III), La(III), and Gd(III) interacting with fused silica/water interfaces held at pH 4 were determined using second harmonic generation and the Eisenthal chi((3)) technique. By examining the relationship between the measured adsorption free energies and the electric double layer interfacial potential at multiple electrolyte concentrations, we elucidate the charge state and possible binding pathways for each ion at the fused silica surface. Al(III) and Sc(III) ions are found to bind to the fused silica surface as fully hydrated trivalent species in a bidentate geometry. In contrast, the Y(III), La(III), and Gd(III) ions are each shown to adsorb to the silica surface in a decreased charge state, but the extent and mode of binding varies with each ion. By quantifying the exponential sensitivity of the surface coverage of the adsorbed ions to their charge state directly at the fused silica/water interface, we provide benchmarks for theory calculations describing the interactions of metal ions with oxide interfaces in geochemistry and hope to improve the prediction of trivalent metal ion transport through groundwater environments. PMID- 22050334 TI - Direct correlation between the facial nerve nucleus and hemifacial seizures associated with a gangliocytoma of the floor of the fourth ventricle: a case report. AB - A dysplastic neuronal lesion of the floor of the fourth ventricle (DNFFV) causes hemifacial seizures (HFS) from early infancy. However, it is still controversial whether HFS is generated by the facial nerve nucleus or cerebellar cortex. In this study, we confirm a direct correlation between the rhythmic activities in the DNFFV and HFS using intraoperative electroencephalography (EEG) and electromyography (EMG) monitoring. Our results support the theory that a DNFFV provokes ipsilateral HFS via the facial nerve nucleus. PMID- 22050335 TI - Interictal pattern-induced visual discomfort and ictal photophobia in episodic migraineurs: an association of interictal and ictal photophobia. AB - BACKGROUND: Pattern-induced visual discomfort and photophobia are frequently observed symptoms in migraineurs. The presumed pathophysiologic mechanisms of pattern glare and photophobia seem to overlap anatomically within the central nervous system. OBJECTIVE: To assess the relationship between interictal pattern induced visual discomfort and ictal photophobia in episodic migraineurs. METHODS: We compared pattern-induced visual discomfort among 3 groups: controls, migraineurs without ictal photophobia (MwoP), and migraineurs with ictal photophobia (MwP). Photophobia was assessed with a validated photophobia questionnaire. Visual discomfort tests were performed using 3 striped patterns with different spatial frequencies. After viewing the patterns for 10 seconds, subjects were asked to report the severity of visual discomfort using 4 scales (none, mild, moderate, and severe) and using a 0-10 visual analog scale (VAS). We compared the proportion of subjects choosing moderate-to-severe discomfort and the median values of VAS scores for each pattern among the 3 groups. RESULTS: We enrolled 35 controls, 18 MwoP, and 44 MwP, and there were no significant differences in clinical features among the 3 groups. MwP reported a significantly higher proportion of moderate-to-severe discomfort and higher median VAS scores than the controls and MwoP did. The intensity of discomfort increased with higher frequency of visual stimuli. CONCLUSIONS: We conclude that MwP experienced more severe pattern-induced visual discomfort as compared with the controls and MwoP. PMID- 22050337 TI - Potential of bacteriophages and their lysins in the treatment of MRSA: current status and future perspectives. AB - Bacteriophages (phages) are viruses that specifically infect and kill bacteria. Lysins are enzymes of bacteriophage origin that cleave covalent bonds in peptidoglycan, thereby inducing rapid lysis of a bacterial cell. As potential antibacterial agents, phages and lysins have some important features in common, especially the capacity to kill antibiotic-resistant bacteria, a narrow antibacterial range, and lack of toxic effects on mammalian cells. In this article we present the staphylococcal phages and their lysins that can be used to combat methicillin-resistant Staphylococcus aureus (MRSA), one of today's most dangerous pathogens. We also discuss the use of phages as vectors specifically delivering different antibacterial agents to bacterial cells. Experimental data show that both phages and lysins could be effective in the treatment of MRSA. PMID- 22050338 TI - Smarter drugs: a focus on pan-specific monoclonal antibodies. AB - Antibodies capable of targeting more than one antigen are envisioned to expand therapeutic efficacy in complex disease settings. Several strategies have been developed to achieve multiple targeting, including antibody mixtures and bispecific formats. In recent years, several dual- and pan-specific antibodies have been described and represent an alternative approach. These antibodies bind to different targets using a single antigen-combining site while maintaining high affinity and specificity, thus challenging the 'one antibody, one antigen' dogma. Despite certain drawbacks, the simple IgG format of this drug class enables rapid progression into the clinic. PMID- 22050340 TI - Gene therapy for rheumatoid arthritis: current status and future prospects. AB - Rheumatoid arthritis (RA) was one of the earliest targets for gene therapy. Since the first clinical trial involving gene therapy in RA was initiated in 1996, eight clinical trials have been conducted assessing gene therapy in RA. Gene therapy has benefited from advances in biologics in terms of the increasing choice of novel, efficient targets to treat RA and also from the optimization of the delivery systems. Several strategies are possible; one of particular interest is local gene therapy directed to rheumatic joints, which avoids systemic vector diffusion. In this review, we discuss (i) gene therapeutic approaches that have been attempted for patients with RA, and (ii) novel strategies that are in development for delivery into patients. We analyze the advantages and disadvantages of the various approaches and how best to optimize them with regard to choosing the most promising vectors and strategies to allow for efficient, long-term, safe delivery of gene therapy in RA. PMID- 22050341 TI - Romidepsin in the treatment of T-cell lymphoma: profile report. PMID- 22050342 TI - Denosumab in the prevention of skeletal-related events in patients with bone metastases from solid tumors: profile report. PMID- 22050339 TI - Targeting T cells with bispecific antibodies for cancer therapy. AB - Bispecific antibodies (BiAbs) offer a unique opportunity to redirect immune effector cells to kill cancer cells. BiAbs combine the benefits of different binding specificities of two monoclonal antibodies (mAbs) into a single construct. This unique feature of BiAbs enables approaches that are not possible with single mAbs. Advances in antibody engineering and antigen profiling of malignant cells have led to the development of a number of BiAb formats and their combinations for redirecting effector cells to tumor targets. There have been significant advances in the design and application of BiAbs for intravenous and local injection.The initial barrier of cytokine storm has been partially overcome by more recent constructs that have improved clinical effectiveness without dose limiting toxicities. Since the recent revival of BiAbs, there has been multiple, ongoing, phase I/II and III trials, and some promising clinical outcomes have been reported in completed clinical studies. This review focuses on arming T cells with BiAbs to create the 'poor man's cytotoxic lymphocyte'. PMID- 22050343 TI - Spotlight on eltrombopag in treatment-refractory chronic primary immune thrombocytopenia. AB - Eltrombopag (Revolade(r)) is an orally bioavailable, low molecular weight, synthetic nonpeptide thrombopoietin receptor agonist, which selectively binds to the transmembrane and juxtamembrane domains of the thrombopoietin receptor on the surface of platelets, megakaryocytes, and megakaryocyte precursor cells, resulting in responses similar to those induced by recombinant human thrombopoietin. Eltrombopag does not compete with thrombopoietin for its binding domain on the thrombopoietin receptor, and is highly selective. This article provides an overview of the pharmacological properties of eltrombopag and reviews the clinical efficacy and tolerability of the drug in adult patients with chronic primary immune thrombocytopenia (ITP). In well designed 6-week and 6-month trials, eltrombopag was more effective than placebo at increasing platelet count and decreasing the incidence of bleeding in patients with treatment-refractory chronic ITP, and was generally well tolerated in these patients. Long-term (median duration 100 weeks) data from a noncomparative trial support these results. Importantly, previous splenectomy did not appear to have an effect on the efficacy of eltrombopag. As the first licensed oral thrombopoietin receptor agonist, eltrombopag may be a more convenient option than other ITP medications; however, it may be a costly option long term, as platelet counts generally return to baseline levels following treatment cessation, implying that continued treatment may be advised. Long-term treatment is often necessary in patients with chronic ITP, as curative rates with any treatment are very low. Eltrombopag was generally well tolerated in clinical trials in patients with chronic ITP. Hepatobiliary abnormalities occurred in a greater proportion of eltrombopag than placebo recipients; however, these were usually mild and reversible. Other potential concerns, such as thromboembolic events, cataracts, and increased bone marrow reticulin, need to be further investigated. Eltrombopag is an effective treatment option for adult patients with chronic ITP and an increased risk of bleeding who are refractory to previous treatments, including splenectomy, as demonstrated in well designed clinical trials. PMID- 22050344 TI - Spotlight on tesamorelin in HIV-associated lipodystrophy. AB - Tesamorelin (EgriftaTM) is a synthetic analog of human growth hormone-releasing hormone (also known as growth hormone-releasing factor) that stimulates the synthesis and release of endogenous growth hormone. It is the first and, so far, only treatment indicated for the reduction of excess abdominal fat in patients with HIV-associated lipodystrophy. This article reviews the pharmacological properties, clinical efficacy and tolerability of tesamorelin in patients with HIV-associated central fat accumulation. Subcutaneous tesamorelin was effective in reducing visceral adipose tissue (VAT), but did not affect subcutaneous adipose tissue to a clinically significant extent in two 26-week, well designed, clinical trials in patients with HIV-associated central fat accumulation. This reduction in VAT was maintained in the longer term in patients who continued to receive tesamorelin until week 52 in the extension phases of the two trials. However, discontinuation of therapy during this period resulted in the reaccumulation of VAT. Tesamorelin therapy was also associated with significant improvements in other body composition measures (e.g. trunk fat and waist circumference) and improvements were generally seen in some body image parameters (e.g. belly image distress). Tesamorelin was generally well tolerated, with treatment-emergent serious adverse events occurring in <4% of patients during 26 weeks of therapy. Most of these events were injection-site reactions or events known to be associated with growth hormone therapy (e.g. arthralgia, headache and peripheral edema). Although long-term clinical experience is needed to further assess the benefits and risks of therapy, current evidence suggests that tesamorelin may be useful for reducing visceral adiposity in patients with HIV associated lipodystrophy, thereby potentially improving self image. PMID- 22050345 TI - Oxidative processes in the Australian marine sponge Plakinastrella clathrata: isolation of plakortolides with oxidatively modified side chains. AB - Sixteen new cyclic peroxides (1-16) with a plakortolide skeleton and the methyl ester derivative of a didehydroplakinic acid (17) were isolated from the Australian sponge Plakinastrella clathrata Kirkpatrick, 1900. Structural elucidation and configurational assignments were based on spectroscopic analysis and comparison with data for previously isolated plakortolides and revealed both phenyl- and methyl-terminating side chains attached to the plakortolide core. Plakortoperoxides A-D (5-8) each contained a second 1,2-dioxine ring; a cis configuration for the side chain endoperoxide ring was determined by a low temperature NMR study and by comparison of chemical shift values with those of reported compounds. An enantioselective HPLC study compared natural plakortoperoxide A with a synthetic sample prepared by cyclization of plakortolide P with singlet oxygen and revealed that the natural sample was a mixture of cis diastereomers at C-15/C18. Four other cyclic peroxides (9-12) possessed a C(9)-truncated side chain terminating in a formyl or carboxylic acid functionality, suggesting that these metabolites may have been formed by oxidative cleavage of the Delta(9,10) bond of diene-functionalized plakortolides. A final group of four metabolites (13-16) with hydroxy or the rare hydroperoxy functionality unexpectedly revealed a C(8) side chain, while the ester (17) represents further structural variation within the growing family of cyclic peroxy sponge metabolites. PMID- 22050346 TI - Association of an increased frequency of CD14+ HLA-DR lo/neg monocytes with decreased time to progression in chronic lymphocytic leukaemia (CLL). PMID- 22050347 TI - Winning the arms race by improving drug discovery against mutating targets. AB - Enzymes are often excellent drug targets. Yet drug pressure on an enzyme target often fosters the rise of cells with resistance-conferring mutations, some of which may compromise fitness and others that compensate to restore fitness. This review presents, first, a structural analysis of a diverse group of wild-type and mutant enzyme targets and, second, an in-depth analysis of five diverse targets to elucidate a broader perspective of the effects of resistance-conferring mutations on protein or organismal fitness. The structural analysis reveals that resistance-conferring mutations may introduce steric hindrance or eliminate critical interactions, as expected, but that they may also have indirect effects such as altering protein dynamics and enzyme kinetics. The structure-based development of the latest generation of inhibitors targeting HIV reverse transcriptase, P. falciparum and S. aureus dihydrofolate reductase, neuraminidase, and epithelial growth factor receptor (EGFR) tyrosine kinase, is highlighted to emphasize lessons that may be applied to future drug discovery to overcome mutation-induced resistance. Successful next-generation drugs tend to be more flexible and exploit a greater number of interactions mimicking those of the substrate with conserved residues. PMID- 22050348 TI - Reengineering a tryptophan halogenase to preferentially chlorinate a direct alkaloid precursor. AB - Installing halogens onto natural products can generate compounds with novel or improved properties. Notably, enzymatic halogenation is now possible as a result of the discovery of several classes of halogenases; however, applications are limited because of the narrow substrate specificity of these enzymes. Here we demonstrate that the flavin-dependent halogenase RebH can be engineered to install chlorine preferentially onto tryptamine rather than the native substrate tryptophan. Tryptamine is a direct precursor to many alkaloid natural products, including approximately 3000 monoterpene indole alkaloids. To validate the function of this engineered enzyme in vivo, we transformed the tryptamine specific RebH mutant (Y455W) into the alkaloid-producing plant Madagascar periwinkle ( Catharanthus roseus ) and observed the de novo production of the halogenated alkaloid 12-chloro-19,20-dihydroakuammicine. While wild-type (WT) RebH has been integrated into periwinkle metabolism previously, the resulting tissue cultures accumulated substantial levels of 7-chlorotryptophan. Tryptophan decarboxylase, the enzyme that converts tryptophan to tryptamine, accepts 7 chlorotryptophan at only 3% of the efficiency of the native substrate tryptophan, thereby creating a bottleneck. The RebH Y455W mutant circumvents this bottleneck by installing chlorine onto tryptamine, a downstream substrate. In comparison with cultures harboring RebH and WT RebF, tissue cultures containing mutant RebH Y455W and RebF also accumulate microgram per gram fresh-weight quantities of 12 chloro-19,20-dihydroakuammicine but, in contrast, do not accumulate 7 chlorotryptophan, demonstrating the selectivity and potential utility of this mutant in metabolic engineering applications. PMID- 22050350 TI - Urology in Asia--Indonesia. PMID- 22050351 TI - Outline of JUA clinical guidelines for benign prostatic hyperplasia. AB - The Japanese Urological Association has developed Clinical Guidelines for Benign Prostatic Hyperplasia (BPH) for men with suspected BPH, which have been abridged and translated into English. This article is a shortened version of the English translation. The Guidelines were formulated on the basis of evidence retrieved from the PubMed database between 1995 and 2009, as well as other relevant sources. The target patients of these Guidelines are men with suspected BPH, and the target users are urologists. A mandatory assessment should include a medical history, a physical examination, the completion of symptom and quality of life questionnaires, urinalysis, prostate ultrasonography, measurement of serum prostate specific antigen and postvoid residual urine, and an uroflowmetry. Optional tests include a bladder diary, the measurement of serum creatinine, and upper urinary tract ultrasonography. Care should be taken to not overlook coexisting diseases such as an infection or malignancy that may obscure the diagnosis. Treatment should consist of conservative therapy or the use of medications such as alpha(1) -adrenoceptor antagonists, or both. The use of 5alpha-reductase inhibitors or anticholinergic agents should be considered in patients with an enlarged prostate (>30 mL) or overactive bladder symptoms (overactive bladder symptom score >= 6), respectively. Surgical intervention is indicated when non-surgical treatments fail to provide sufficient symptomatic relief and bladder outlet obstruction is highly suspected. PMID- 22050352 TI - Editorial Comment to Impact of diabetes mellitus on recurrence and progression in patients with non-muscle invasive bladder carcinoma: a retrospective cohort study. PMID- 22050354 TI - Is there a 'low-risk' drinking level for youth? The risk of acute harm as a function of quantity and frequency of drinking. AB - INTRODUCTION AND AIMS: Drinking guidelines have rarely provided recommendations for different age groups despite evidence of significant age effects on alcohol consumption and related risks. This study attempted to quantify the degree of risk associated with lower levels of consumption for people under 25 years of age, with the broader purpose of informing the development of Canadian low-risk drinking guidelines. DESIGN AND METHODS: A random community-based sample of 540 youth aged 16-23 (54.4% female) completed an interview concerning alcohol consumption patterns and a broad range of acute health and social harms. Logistic regression analyses were designed to test whether there were discernible thresholds of risk as a function of both gender and age. RESULTS: A significant proportion of young people consumed in excess of adult drinking limits recommended by the Centre for Addiction and Mental Health (CAMH) to minimise risk of alcohol-related harm. Compared with abstainers, rates of reported harm increased linearly with increasing frequency and quantity levels. However, problems were most strongly associated with consumption in excess of two drinks per occasion and a frequency of more than once a week. No independent effects of age or gender were identified. DISCUSSION AND CONCLUSIONS: The CAMH guidelines for adult drinkers do not adequately address acute risks for young people. More specific guideline recommendations for young people could be considered with a more prominent focus on drinking quantity (one to two drinks per occasion), and a recommended frequency of consumption (once a week). PMID- 22050356 TI - Fourth congress of the European association for veterinary pharmacology and toxicology. PMID- 22050355 TI - Sialochemistry and cortisol levels in patients with Sjogren's syndrome. AB - OBJECTIVES: (i) To determine whether salivary cortisol and electrolyte levels differ between patients with Sjogren's syndrome (SjS) and healthy individuals. (ii) To assess correlations between whole-saliva cortisol and some clinical manifestations in patients with SjS. METHODS: A total of 24 healthy women (mean age 49.3+/-9.8) served as controls (C) vis-a-vis 17 patients with SjS (mean age 55.5+/-15.7). Salivary cortisol concentration was determined, and sialochemistry analysis was performed. RESULTS: Significantly lower saliva flow rates and higher salivary chloride (Cl(-) ), potassium (K(+) ), and Ca(2+) levels were found in the SjS group. No significant differences or correlations were found in other parameters, including sodium (Na(+) ), magnesium (Mg(2+) ), phosphate ((-) ), urea (U), and salivary cortisol levels. CONCLUSION: Increased whole-salivary output of Cl(-) and K(+) in SjS may reflect release from apoptotic rests of acinar cells after secondary necrosis. Normal levels of salivary Na(+) , Mg(2+) , and (-) argue against concentration effect, deranged tubular function or cortisol (mineralocorticosteroid) effect as the cause for these findings. Increased salivary Ca(2+) levels probably reflect leakage of plasma Ca(2+) through the injured oral mucosa in SjS. In spite of disease-associated stress, salivary cortisol, a stress biomarker, was not increased, suggesting insufficient hypothalamus-pituitary-adrenal (HPA) axis response and/or local consumption of cortisol by lymphocyte infiltrates. PMID- 22050358 TI - DNA building blocks: keeping control of manufacture. AB - Ribonucleotide reductase (RNR) is the only source for de novo production of the four deoxyribonucleoside triphosphate (dNTP) building blocks needed for DNA synthesis and repair. It is crucial that these dNTP pools are carefully balanced, since mutation rates increase when dNTP levels are either unbalanced or elevated. RNR is the major player in this homeostasis, and with its four different substrates, four different allosteric effectors and two different effector binding sites, it has one of the most sophisticated allosteric regulations known today. In the past few years, the structures of RNRs from several bacteria, yeast and man have been determined in the presence of allosteric effectors and substrates, revealing new information about the mechanisms behind the allosteric regulation. A common theme for all studied RNRs is a flexible loop that mediates modulatory effects from the allosteric specificity site (s-site) to the catalytic site for discrimination between the four substrates. Much less is known about the allosteric activity site (a-site), which functions as an on-off switch for the enzyme's overall activity by binding ATP (activator) or dATP (inhibitor). The two nucleotides induce formation of different enzyme oligomers, and a recent structure of a dATP-inhibited alpha(6)beta(2) complex from yeast suggested how its subunits interacted non-productively. Interestingly, the oligomers formed and the details of their allosteric regulation differ between eukaryotes and Escherichia coli. Nevertheless, these differences serve a common purpose in an essential enzyme whose allosteric regulation might date back to the era when the molecular mechanisms behind the central dogma evolved. PMID- 22050359 TI - Maternal report on child outcome after a community-based program following intimate partner violence. AB - BACKGROUND: This study examined the perceived effectiveness of a 15-week community-based program for 46 children exposed to intimate partner violence (IPV) and their mothers. AIMS: The primary aims were to describe the children who entered one of the existing community-based programs in terms of behavioral problems and to evaluate the impact of the program on children's general behavioral functioning as assessed by their mothers. RESULTS: Children's rated behavioral problems (SDQ) dropped following treatment; the effect size was in the medium range. The social impairment caused by the problems decreased as well. The effect regarding behavioral problems was not related to the degree of exposure to IPV or the mothers own changes in trauma symptoms following treatment. Results were analyzed as well at the individual level with the Reliable Change Index (RCI), which showed that the majority of children were unchanged following treatment. CONCLUSIONS: One implication from the study is the need for baseline screening and assessment. About half of the current sample had a clinical symptom picture indicating the need for specialized psychiatric/psychotherapeutic treatment. Furthermore, the reduction in behavioral problems was significant but many children still had high levels of behavioral problems after treatment, indicating a need of a more intense or a different type of intervention. PMID- 22050360 TI - Treatment of steroid-unresponsive optic neuritis with plasma exchange. AB - OBJECTIVES: Until now, the significance of plasma exchange (PE) as a treatment for steroid-unresponsive optic neuritis (ON) is still unclear because placebo controlled and larger studies are missing. We report our experience with 23 patients treated by PE due to steroid-unresponsive ON. MATERIALS AND METHODS: Patients were admitted to the University Medical Center Hamburg-Eppendorf between 2006 and 2010 with a visual acuity of <50% on the affected eye following steroid treatment. Ten patients suffered from RR-MS, one from neuromyelitis optica, and 12 patients developed ON as a clinically isolated syndrome. Routinely, they were treated with five cycles of PE. Visual acuity was measured before and directly after PE and during follow-up (first follow-up after 50 days, second follow-up after 174 days). RESULTS: Altogether, 70% of our patients improved after PE, 69% of them showed a good or very good response to therapy. Patients who improved well after PE (n = 11) showed a mean visual acuity of 16% before PE compared to 45% immediately after PE and 60% at the first follow-up. No serious adverse events occurred. CONCLUSIONS: To our knowledge, our study is the largest case series of patients with steroid-unresponsive ON treated with PE. Based on our experience, we conclude that PE is an important treatment option for patients with steroid-unresponsive ON although placebo-controlled studies are missing until now. PMID- 22050361 TI - Administration of flutamide alters sperm ultrastructure, sperm plasma membrane integrity and its stability, and sperm mitochondrial oxidative capability in the boar: in vivo and in vitro approach. AB - Our previous work has shown that an anti-androgen flutamide administered pre- and post-natally induced adverse effects on the epididymal morphology and function of adult boars. The present investigation is aimed to understand the effect of flutamide and its metabolite on changes in sperm plasma membrane integrity and its stability, changes in mitochondrial oxidative capability and frequency of abnormal sperm. In vivo effects of flutamide (50 mg/kg b.w.) on sperm ultrastructure were examined by electron microscopic observations. In vitro effects of 5, 50 and 100 MUg/ml hydroxyflutamide, administered for 2 and 24 h, on sperm plasma membrane integrity were measured by LIVE/DEAD Sperm Vitality kit, while those on sperm membrane stability and mitochondrial oxidoreductive activity were investigated using Merocyanine 540 and NADH tests, respectively. The incidence of abnormal spermatozoa increased significantly (p < 0.05) in flutamide treated boars compared with controls. In an in vitro approach, low dose of hydroxyflutamide in 2-h incubations appeared less effective in altering the sperm plasma membrane integrity and its stability than two higher doses used (p < 0.05). No further decrease in the membrane integrity was found when the effect of anti-androgen lasted for 24 h. On the other hand, a decrease in sperm membrane destabilization and mitochondrial oxidoreductive activity was strengthened after 24 h of hydroxyflutamide administration (p < 0.05). Characterization of sperm parameters with regard to oxidative capability of mitochondria, plasma membrane changes and sperm ultrastructure provides novel data on the boar sperm sensitivity to anti-androgen action. Results indicate high sensitivity of boar spermatozoa to androgen withdrawal. PMID- 22050362 TI - Lateral epicondylalgia: a structured programme better than corticosteroids and NSAID. AB - AIM: To evaluate whether patients with lateral epicondylalgia had less pain or function loss two years following treatment by a structured programme and if the number of recurrent episodes and sick leave days differed compared with a control group. SUBJECTS: All of the patients were diagnosed by a physician with the diagnosis code M77.1 (lateral epicondylitis). The intervention group (n = 103) was treated by a physiotherapist and an occupational therapist with a home training programme that included ergonomic advice. Wrist supports and/or night bandages were also available. Controls (n = 194) were diversely treated by different professionals. MAJOR FINDINGS: In the total study group (n = 297), 54% of the patients experienced pain and 55% experienced function loss after two years. The intervention group had less pain than patients treated with corticosteroid injections (p < 0.0001) or NSAIDs (p = 0.048) and experienced better function than those treated with corticosteroid injections (p = 0.002). The intervention group had a lower recurrence (p < 0.0001) and fewer sick leave days at the time of the visit to the health care centre (p = 0.005). PRINCIPAL CONCLUSIONS: A structured treatment programme was more effective than corticosteroid injections and NSAIDs. Patients did not require additional treatment or sick leave and had learned self-treatment of the disorder. PMID- 22050363 TI - Unique DNA binding mode of antitumor trinuclear tridentate platinum(II) compound. AB - The new trinuclear tridentate Pt(II) complex [Pt(3)Cl(3)(hptab)](3+) (1; hptab = N,N,N',N',N'',N''-hexakis(2-pyridylmethyl)-1,3,5-tris(aminomethyl)benzene) exhibits promising cytotoxic effects in human and mouse tumor cells including those resistant to conventional cisplatin (Dalton Trans. 2006, 2617; Chem. Eur. J. 2009, 15, 5245). The present study is focused on the molecular pharmacology of 1, in particular on its interactions with DNA (which is the major pharmacological target of platinum antitumor drugs), to elucidate more deeply the mechanism underlying its antitumor effects. Results obtained with the aid of methods of molecular biophysics and pharmacology reveal new details of DNA modifications by 1. Complex 1 binds to DNA forming in the absence of proteins and molecular crowding agents mainly trifunctional intrastrand cross-links. In these DNA adducts all three Pt(II) centers of 1 are coordinated to DNA base residues, which leads to extensive conformational alterations in DNA. An intriguing aspect of the DNA-binding mode of this trinuclear Pt(II) complex 1 is that it can cross-link proteins to DNA. Even more interestingly, 1 can cross-link in the presence of molecular crowding agent, which mimics environmental conditions in cell nucleus, two DNA duplexes in a high yield--a feature observed for the first time for antitumor trinuclear platinum complexes. Thus, the concept for the design of agents capable of forming intramolecular tridentate DNA adducts, DNA-protein and interduplex DNA-DNA cross-links based on trinuclear tridentate Pt(II) complexes with semirigid aromatic linkers may result in new compounds which exhibit a variety of biological effects and can be also useful in nucleic acids research. PMID- 22050364 TI - Extended GTST-MLD for aerospace system safety analysis. AB - The hazards caused by complex interactions in the aerospace system have become a problem that urgently needs to be settled. This article introduces a method for aerospace system hazard interaction identification based on extended GTST-MLD (goal tree-success tree-master logic diagram) during the design stage. GTST-MLD is a functional modeling framework with a simple architecture. Ontology is used to extend the ability of system interaction description in GTST-MLD by adding the system design knowledge and the past accident experience. From the level of functionality and equipment, respectively, this approach can help the technician detect potential hazard interactions. Finally, a case is used to show the method. PMID- 22050365 TI - Psychological resistance to insulin therapy in adults with type 2 diabetes: mixed method systematic review. AB - AIM: This paper is a report of a review that aimed to describe the phenomenon of psychological resistance to insulin therapy from the perspective of adults with type 2 diabetes mellitus. BACKGROUND: Although the benefits of insulin for people with diabetes who are poorly controlled by oral agents have been established, delay in transition to insulin treatment is common. An understanding of the barriers to insulin from the client's viewpoint provides information to facilitate appropriate and effective care. DATA SOURCES: Searches were carried out between 1999 and 2009 using computerized databases, three in English language and one in Chinese. REVIEW METHODS: Review design was a mixed-method systematic review, and data abstraction and synthesis were undertaken by thematic synthesis. Reviewed articles were restricted to adults with type 2 diabetes and published in English or Chinese. RESULTS: Sixteen articles were included. For adults with type 2 diabetes, psychological resistance to insulin therapy could be explained by five themes. Three themes were categorized as cognitive appraisal, including 'people do not see the necessity for insulin and actively seek ways to control blood sugars without insulin', 'people have a holistic view of the consequences of insulin' and 'people see insulin therapy as less feasible'. Two themes were categorized as emotional reactions: 'people see insulin as a source of fear/anxiety', and 'the necessity to start insulin therapy has a very negative connotation for them and is associated with dysfunctional emotions'. CONCLUSION: Psychological resistance to insulin therapy can result from a range of personal viewpoints involving cognitive appraisal and/or emotional reactions. PMID- 22050366 TI - Implementation of two tests for measuring sensitivity to temporal fine structure. AB - OBJECTIVE: To implement two methods for measuring sensitivity to temporal fine structure (TFS) for use in assessing effects of hearing loss and age that may not be apparent from the audiogram. DESIGN: The TFS1 test was described by Moore and Sek (2009). The task is to discriminate a harmonic complex tone from a tone in which all frequency components are shifted upwards by the same amount in Hz. The TFSLF test was described by Hopkins and Moore (2010a). The task is to detect changes in lateral position of a binaurally presented tone based on interaural phase difference (IPD). Both tests have been implemented in software that can be run on a PC with a good-quality sound card. The software includes a routine for measuring the absolute threshold at the test frequency. RESULTS: For each test, an experimental run at a single frequency takes about three minutes. Practice tasks (frequency discrimination of pure tones for TFS1 and discrimination of changes in lateral position based on interaural level difference for TFSLF) are also implemented that are similar to the main task, but easier. CONCLUSIONS: The software implementation allows sensitivity to TFS to be measured quickly without a requirement for specialized equipment. PMID- 22050367 TI - Systems-wide proteomic analysis in mammalian cells reveals conserved, functional protein turnover. AB - The turnover of each protein in the mammalian proteome is a functionally important characteristic. Here, we employed high-resolution mass spectrometry to quantify protein dynamics in nondividing mammalian cells. The ratio of externally supplied versus endogenous amino acids to de novo protein synthesis was about 17:1. Using subsaturating SILAC labeling, we obtained accurate turnover rates of 4106 proteins in HeLa and 3528 proteins in C2C12 cells. Comparison of these human and mouse cell lines revealed a highly significant turnover correlation of protein orthologs and thus high species conservation. Functionally, we observed statistically significant trends for the turnover of phosphoproteins and gene ontology categories that showed extensive covariation between mouse and human. Likewise, the members of some protein complexes, such as the proteasome, have highly similar turnover rates. The high species conservation and the low complex variances thus imply great regulatory fine-tuning of protein turnover. PMID- 22050368 TI - Tissue Doppler and strain rate imaging detect improvement of myocardial function in iron deficient patients with congestive heart failure after iron replacement therapy. AB - BACKGROUND: Iron deficiency may contribute to diminished exercise tolerance in patients with congestive heart failure (CHF) even in absence of anemia. The aim of this study was to evaluate the effect of correction of iron deficiency on functional capacity and myocardial function in patients with CHF. METHODS: We studied 40 patients with ejection fraction <40%, hemoglobin% >12 g/dL, serum ferritin <100 ug/L, and transferrin saturation <20%. Patients received 200 mg weekly doses of iron dextran complex until serum ferritin level was between 200 and 300 ug/L or transferrin saturation level was between 30% and 40%. Transthoracic echocardiogram, tissue Doppler imaging, peak systolic strain rate, and 6 minute walk test were performed before iron therapy and at 12-week follow up. Peak early diastolic myocardial tissue velocity (E'), peak late diastolic myocardial tissue velocity (A'), and peak systolic myocardial tissue velocity (S') were measured. RESULTS: There was a significant improvement of New York Heart Association functional class (3.0 +/- 0.4 vs. 2.1 +/- 0.3, P < 0.05) and 6minutes walk distance (322 +/- 104 vs. 377 +/- 76, P < 0.01) from rest to follow up, respectively. Ejection fraction did not change significantly (32 +/- 8% vs. 34 +/- 9%, respectively). There was a significant improvement of S'-wave (3.0 +/- 0.8 cm/sec vs. 6.0 +/- 1.2 cm/sec, P < 0.05), E/E' ratio (22 +/- 3 vs. 13 +/- 3, P < 0.05), and peak systolic strain rate (-0.72 +/- 0.11/s vs. -1.09 +/- 0.37/s, P < 0.05) from baseline to follow-up, respectively. CONCLUSION: Correction of iron deficiency improves functional class and walking distance in nonanemic iron deficient patients with systolic heart failure. Tissue Doppler and strain rate demonstrated a significant improvement of diastolic and systolic function after therapy despite lack of improvement of ejection fraction. (Echocardiography 2012;29:13-18). PMID- 22050369 TI - Pentanuclear cyanide-bridged complexes based on highly anisotropic Co(II) seven coordinate building blocks: synthesis, structure, and magnetic behavior. AB - Pentagonal-bipyramidal complexes [Co(DABPH)X(H(2)O)]X [X = NO(3) (1), Br (2), I (3)] were synthesized, and their magnetic behavior was investigated. Simulation of the magnetization versus temperature data revealed the complexes to be highly anisotropic (D ~ +30 cm(-1)) and the magnitude of the anisotropy to be independent of the nature of the axial ligands. The reaction of 1 with K(3)[M(CN)(6)] (M = Cr, Fe) produces the pentametallic clusters [{Co(DABPH)}(3){M(CN)(6)}(2)(H(2)O)(2)] [M = Cr (4), Fe (5)]. Both clusters consist of three {Co(DABPH)} moieties separated by two {M(CN)(6)} fragments. In 4, the central and terminal Co(II) ions are bound to cyanide groups cis to one another on the bridging {Cr(CN)(6)}, whereas in 5, the connections are via trans cyanide ligands, resulting in the zigzag and linear structures observed, respectively. Magnetic investigation revealed ferromagnetic intramolecular interactions; however, the ground states were poorly isolated because of the large positive local anisotropies of the Co(II) ions. The effects of the local anisotropies appeared to dominate the behavior in 5, where the magnetic axes of the Co(II) ions were approximately colinear, compared to 4, where they were closer to orthogonal. PMID- 22050370 TI - In honour of professor Jindrich (Henry) Kopecek, recipient of the Journal of Drug Targeting's Life-Time Achievement Award for 2011. PMID- 22050371 TI - Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow up study. AB - PURPOSE: To evaluate the long-term efficacy and tolerability of adjunctive levetiracetam (LEV) in patients with uncontrolled idiopathic generalized epilepsy (IGE). METHODS: This phase III, open-label, long-term, follow-up study (N167; NCT00150748) enrolled patients (4 to <65 years) with primary generalized seizures (tonic-clonic, myoclonic, absence). Patients received adjunctive LEV at individualized doses (1,000-4,000 mg/day; 20-80 mg/kg/day for children/adolescents weighing <50 kg). Efficacy results are reported for all seizure types [intention-to-treat (ITT) population, N = 217] and subpopulations with tonic-clonic (n = 152), myoclonic (n = 121), and/or absence (n = 70) seizures at baseline. KEY FINDINGS: One hundred twenty-five (57.6%) of 217 patients were still receiving treatment at the end of the study. Mean (standard deviation, SD) LEV dose was 2,917.5 (562.9) mg/day. Median (Q1-Q3) exposure to LEV was 2.1 (1.5-2.8) years, and the maximum duration was 4.6 years. Most patients were taking one (124/217, 57.1%) or >=2 (92/217, 42.4%) concomitant antiepileptic drugs (AEDs). Seizure freedom of >=6 months (all seizure types; primary efficacy end point) was achieved by 122 (56.2%) of 217 patients, and 49 (22.6%) of 217 patients had complete seizure freedom. Seizure freedom of >=6 months from tonic-clonic, myoclonic, and absence seizures was achieved by 95 (62.5%) of 152, 75 (62.0%) of 121, and 44 (62.9%) of 70 patients, respectively. Mean (SD) maximum seizure freedom duration was 371.7 (352.4) days. At least one treatment-emergent adverse event (TEAE) was reported by 165 (76%) of 217 patients; most TEAEs were mild/moderate in severity, with no indication of an increased incidence over time. Seventeen (7.8%) of 217 patients discontinued medication because of TEAEs. The most common psychiatric TEAEs were depression (16/217, 7.4%), insomnia (9/217, 4.1%), nervousness (8/217, 3.7%), and anxiety (7/217, 3.2%). SIGNIFICANCE: Adjunctive LEV (range 1,000-4,000 mg/day) demonstrated efficacy as a long-term treatment for primary generalized seizures in children, adolescents, and adults with IGE, and was well tolerated. PMID- 22050372 TI - Photochemistry and photophysics of n-butanal, 3-methylbutanal, and 3,3 dimethylbutanal: experimental and theoretical study. AB - Dilute mixtures of n-butanal, 3-methylbutanal, and 3,3-dimethylbutanal in synthetic air, different N(2)/O(2) mixtures, and pure nitrogen (up to 100 ppm) were photolyzed with fluorescent UV lamps (275-380 nm) at 298 K. The main photooxidation products were ethene (n-butanal), propene (3-methylbutanal) or i butene (3,3-dimethylbutanal), CO, vinylalcohol, and ethanal. The photolysis rates and the absolute quantum yields were found to be dependent on the total pressure of synthetic air but not of nitrogen. At 100 Torr, the total quantum yield Phi(100) = 0.45 +/- 0.01 and 0.49 +/- 0.07, whereas at 700 Torr, Phi(700) = 0.31 +/- 0.01 and 0.36 +/- 0.03 for 3-methylbutanal and 3,3-dimethybutanal, respectively. Quantum yield values for n-butanal were reported earlier by Tadic et al. (J. Photochem. Photobiol. A2001143, 169-179) to be Phi(100) = 0.48 +/- 0.02 and Phi(700) = 0.32 +/- 0.01. Two decomposition channels were identified: the radical channel RCHO -> R + HCO (Norrish type I) and the molecular channel CH(3)CH(CH(3))CH(2)CHO -> CH(2)CHCH(3) + CH(2)?CHOH or CH(3)C(CH(3))(2)CH(2)CHO > CHC(CH(3))CH(3) + CH(2)?CHOH, (Norrish type II) having the absolute quantum yields of 0.123 and 0.119 for 3-methybutanal and 0.071 and 0.199 for 3,3 dimethylbutanal at 700 Torr of synthetic air. The product ethenol CH(2)?CHOH tautomerizes to ethanal. We have performed ab initio and density functional quantum (DFT) chemical computations of both type I and type II processes starting from the singlet and triplet excited states. We conclude that the Norrish type I dissociation produces radicals from both singlet and triplet excited states, while Norrish type II dissociation is a two-step process starting from the triplet excited state, but is a concerted process from the singlet state. PMID- 22050373 TI - Implementation of the harmonized EU isotretinoin Pregnancy Prevention Programme: a questionnaire survey among European regulatory agencies. AB - BACKGROUND: There is little information on the status of the implementation of the isotretinoin Pregnancy Prevention Programme (PPP) in the EU, and on compliance with this programme by the regulatory agencies. OBJECTIVE: The aim of the study was to obtain information on implementation of the harmonized PPP of isotretinoin in the EU member states plus Norway and Iceland. MATERIALS AND METHODS: In January 2009, a questionnaire (request for non-urgent information [NUI]) was sent to all 25 EU member states, plus Norway and Iceland, to collect information on the implementation status of the PPP and its effectiveness. RESULTS: The response rate was 82% (22 of the 27 countries). In 21 of the 27 member states, isotretinoin is marketed and the PPP is in force, and in 18 of the 22 responding countries, the total required elements (seven) following a formal EU review are incorporated in the PPP. Seven member states had additional measures in place. In spite of implementation of the PPP and additional measures, a total of 143 isotretinoin-exposed pregnancies have been reported in 16 of the 22 responding member states since implementation of the harmonized PPP. CONCLUSIONS: Despite implementation of the isotretinoin PPP in most member states, isotretinoin-exposed pregnancies were reported. This has led some member states to implement additional measures to the PPP, resulting in inconsistency with the approach agreed in 2003 following the European-wide review. It has been further suggested that common elements should be developed for PPPs for all medicines that are known to carry a high teratogenic risk. PMID- 22050374 TI - Interleukin-6 in oral diseases: a review. AB - Interleukin-6 (IL-6) is a pleomorphic cytokine involved in a number of physiologic and pathologic processes including response to trauma and infection and development and progression of inflammation and malignancy. IL-6 is emerging as an important mediator and novel therapeutic target for chronic inflammatory diseases and cancer. The present study reviews the available evidence regarding the association between IL-6 and a range of oral diseases including infections (periodontal disease and endodontic infections), immunologically mediated disorders (oral lichen planus and Sjogren's syndrome) and malignancy (oral cancer and precancer). The role of common genetic variants of IL-6 in determining individual susceptibility to certain oral diseases, as well as novel therapeutic strategies based on IL-6 inhibition are also discussed. PMID- 22050376 TI - Low T2 signal intensity on magnetic resonance imaging: a feature of minimal fat angiomyolipomas. PMID- 22050378 TI - Distinctive attributes of beta-lactam target proteins in Acinetobacter baumannii relevant to development of new antibiotics. AB - Multi-drug-resistant forms of the Gram-negative pathogen Acinetobacter baumannii are an emerging threat to human health and further complicate the general problem of treating serious bacterial infections. Meeting this challenge requires an improved understanding of the relationships between the structures of major therapeutic targets in this organism and the activity levels exhibited against it by different antibiotics. Here we report the first crystal structures of A. baumannii penicillin-binding proteins (PBPs) covalently inactivated by four beta lactam antibiotics. We also relate the results to kinetic, biophysical, and computational data. The structure of the class A protein PBP1a was solved in apo form and for its covalent conjugates with benzyl penicillin, imipenem, aztreonam, and the siderophore-conjugated monocarbam MC-1. It included a novel domain genetically spliced into a surface loop of the transpeptidase domain that contains three conserved loops. Also reported here is the first high-resolution structure of the A. baumannii class B enzyme PBP3 in apo form. Comparison of this structure with that of MC-1-derivatized PBP3 of Pseudomonas aeruginosa identified differences between these orthologous proteins in A. baumannii and P. aeruginosa. Thermodynamic analyses indicated that desolvation effects in the PBP3 ligand binding sites contributed significantly to the thermal stability of the enzyme antibiotic covalent complexes. Across a significant range of values, they correlated well with results from studies of inactivation kinetics and the protein structures. The structural, biophysical, and computational data help rationalize differences in the functional performance of antibiotics against different protein targets and can be used to guide the design of future agents. PMID- 22050377 TI - Using the heat-shock response to discover anticancer compounds that target protein homeostasis. AB - Unlike normal tissues, cancers experience profound alterations in protein homeostasis. Powerful innate adaptive mechanisms, especially the transcriptional response regulated by Heat Shock Factor 1 (HSF1), are activated in cancers to enable survival under these stressful conditions. Natural products that further tax these stress responses can overwhelm the ability to cope and could provide leads for the development of new, broadly effective anticancer drugs. To identify compounds that drive the HSF1-dependent stress response, we evaluated over 80,000 natural and synthetic compounds as well as partially purified natural product extracts using a reporter cell line optimized for high-throughput screening. Surprisingly, many of the strongly active compounds identified were natural products representing five diverse chemical classes (limonoids, curvularins, withanolides, celastraloids, and colletofragarones). All of these compounds share the same chemical motif, an alpha,beta-unsaturated carbonyl functionality, with strong potential for thiol-reactivity. Despite the lack of a priori mechanistic requirements in our primary phenotypic screen, this motif was found to be necessary albeit not sufficient, for both heat-shock activation and inhibition of glioma tumor cell growth. Within the withanolide class, a promising therapeutic index for the compound withaferin A was demonstrated in vivo using a stringent orthotopic human glioma xenograft model in mice. Our findings reveal that diverse organisms elaborate structurally complex thiol-reactive metabolites that act on the stress responses of heterologous organisms including humans. From a chemical biology perspective, they define a robust approach for discovering candidate compounds that target the malignant phenotype by disrupting protein homeostasis. PMID- 22050379 TI - Do cognitive functions in obsessive-compulsive disorder change after treatment? A systematic review and a double case report. AB - BACKGROUND: Neuropsychological and neuroimaging studies have documented that patients with obsessive-compulsive disorder (OCD) have cognitive difficulties dependent upon fronto-striatal circuits in the brain. It is, however, unclear whether the cognitive difficulties change after treatment. Answering this question could help establish whether cognitive difficulties in OCD are state dependent or more trait-like. AIM: To determine whether cognitive functions in OCD change after treatment, based on a systematic literature review, supplemented by a double case report of monozygotic twins with OCD. METHODS: For the literature review, systematic searches were conducted in PubMed, Embase and PsycINFO from the earliest dates available to September 2010. For the double case report, monozygotic twins underwent blood samples and magnetic resonance imaging before treatment with cognitive behavioral therapy (CBT), antidepressants and small doses of antipsychotic medication. Before and after CBT they were assessed with measures of content and severity of OCD symptoms, and with a comprehensive battery of neuropsychological tests to assess cognitive functions. RESULTS: Results from the studies under review (n = 14) were so inconsistent that it could not be concluded whether cognitive functions in OCD change after treatment. The twins improved some of their cognitive functions after treatment. CONCLUSIONS: A better understanding of whether cognitive dysfunctions in OCD are state dependent or trait-like could bring important implications in understanding the pathology and future treatment of OCD. PMID- 22050380 TI - Advances in companion animal medicine and surgery. PMID- 22050382 TI - Jadomycins derived from the assimilation and incorporation of norvaline and norleucine. AB - Streptomyces venezuelae ISP5230 is recognized for the production of chloramphenicol and the jadomycin family of natural products. The jadomycins are angucycline natural products containing a unique oxazolone ring incorporating an amino acid present in the minimal culture media. Substitution of different amino acids results in products of varying biological activity. Analysis of cultures of S. venezuelae ISP5230 incubated with l- and d-norvaline and l- and d-norleucine indicated that only the d-configured amino acids were incorporated into the natural products. Subsequently, jadomycin DNV and jadomycin DNL were isolated and characterized (titers 4 and 9 mg L(-1), respectively). The compounds were evaluated in the National Cancer Institute cell line cancer growth inhibition and cytotoxicity screens, for antimicrobial activity against selected Gram-positive and Gram-negative bacteria, and as DNA-cleavage agents in vitro. PMID- 22050383 TI - Investigation into developmental potential and nuclear/mitochondrial function in early wood and plains bison hybrid embryos. AB - Studies to date have shown that bison embryo development in vitro is compromised with few embryos developing to the blastocyst stage. The aim of this study was to use bison-cattle hybrid embryos, an interspecific cross that is known to result in live offspring in vivo, as a model for assessing species-specific differences in embryo development in vitro. Cattle oocytes fertilized with cattle, plains bison and wood bison sperm were assessed for various developmental parameters associated with embryo quality, including cell number, apoptosis and ATP content. Decreased development to the blastocyst stage was observed in hybrid wood bison embryos compared with the other treatment groups. Although both wood bison and plains bison hybrid blastocysts had significantly lower cell numbers than cattle blastocysts, only wood bison hybrid blastocysts had a greater incidence of apoptosis than cattle blastocysts. Among the treatment groups, ATP levels and expression profiles of NRF1, TFAM, MT-CYB, BAX and BCL2 were not significantly different in both 8- to 16-cell stage and blastocyst stage embryos. These data provide evidence of decreased developmental competence in the wood bison hybrid embryos, owing to inadequate culture conditions that have increased apoptotic events. PMID- 22050384 TI - Secondary primary malignancies in patients with multiple myeloma treated with high-dose chemotherapy and autologous blood stem cell transplantation. PMID- 22050385 TI - Nestin is induced by hypoxia and is attenuated by hyperoxia in Muller glial cells in the adult rat retina. AB - This study investigated the reactive changes in Muller glial cells and astrocytes of the rat retinae, which had been subjected either to hypoxia or to hypoxia followed by hyperoxia treatments. Fifteen rats were used. Ten rats were exposed to 9% O(2) for 2 h. Of these, five rats were killed at 24 h later; the remaining five rats were immediately exposed to 80% O(2) for 2 h and then killed 24 h later. Double immunofluorescence was carried out between nestin and glutamine synthetase (GS) and between glial fibrilary acidic proteins (GFAP) and GS in normal and pathological retinae. Enhanced nestin expression was observed in reactive astrocytes following hypoxia treatment as revealed in whole mount sections. A novel finding was the induction of nestin expression in Muller glial cells. Remarkably, the nestin immunostaining was downregulated to levels comparable to those of the normal rats with immediate hyperoxia treatment. Induced nestin expression by hypoxia colabelled with GFAP in astrocytes, however, remained unaffected after hyperoxia treatment. The induced expression of nestin in Muller glial cells and astrocytes in hypoxia and differential downregulation after hyperoxia treatment suggest a structural plasticity of the cytoskeletal framework of these cells. The differential response after hyperoxia treatment may be related to the functional states of the cells. PMID- 22050386 TI - Genetic polymorphisms of human beta-defensins in patients with ischemic stroke. AB - OBJECTIVES AND METHODS: Genetic predisposition of the inflammatory host response may affect the development of stroke. On the basis of the theory of infectious burden and risk of stroke, we considered it of interest to investigate the relevance of the single-nucleotide polymorphisms (SNPs) in the DEFB1 gene and the copy number variant (CNV) of the DEFB4 genes in ischemic stroke. RESULTS: There were no significant differences in the genotype frequencies of the three SNPs of the DEFB1 gene between the patients with stroke (n = 312) and the healthy blood donors (n = 221). However, a higher frequency of a lower (<4) copy number of the DEFB4 gene was observed in the patients with ischemic stroke as compared with the healthy controls (40% vs 24%, respectively). Additionally, low plasma concentrations of hBD-2 (187 +/- 20 pg/ml) were characteristic of the patients with fewer than four copy numbers relative to those with more than four copy numbers (385 +/- 35 pg/ml). CONCLUSIONS: The low copy number of the DEFB4 gene, involving a weakened antimicrobial defense of the host, might be important in the pathogenesis of stroke. PMID- 22050387 TI - Degenerative changes of the temporomandibular joint. Relationship to ethnicity, sex and occlusal supporting zones based on a skull material. AB - OBJECTIVE: The first aim of this study was to examine a contemporary human skull material for possible ethnic differences in respect of degenerative changes in the temporomandibular joints (TMJs). A second aim was to see if there was any correlation between such changes and occlusal support in any of the two groups and, if so, if this correlation was sex-related. MATERIALS AND METHODS: The material consisted of 129 Caucasian skulls and 76 skulls from Afro-Americans. Ninety-four of the Caucasian skulls came from males (73%) and the corresponding figure for the Afro-Americans was 40 (53%). Their mean age at death was 46 years (range: 19-89 years) and 37 years (range: 18-70 years), respectively. RESULTS: Dental status was in general poor and 13% of the Afro-Americans and 26% of the Caucasians were edentulous. Form and surface changes of the TMJs were more common in the present material compared to most previous studies. No differences could be found between the two ethnic groups in respect of degenerative joint changes in the TMJs. In men, no correlation of clinical relevance could be found between severity of joint changes and occlusal support. However, in both Caucasian and Afro-American women, such a correlation was obvious, especially in higher age. CONCLUSIONS: The present findings give no evidence for any differences in the prevalence of degenerative changes in the TMJs in Caucasians and Afro-Americans. The strong correlation found between such changes and occlusal support in women but not in men might be explained by hormonal differences. PMID- 22050388 TI - Catestatin is useful in detecting patients with stage B heart failure. AB - Screening patients with stage B heart failure(HF) may be one strategy for reducing human morbidity. To describe catestatin levels in different stages of HF and evaluate the diagnostic utility of catestatin for detecting stage B HF, we included 300 patients. Catestatin, BNP testing and echocardiogram were performed. Our studies showed catestatin decreased gradually from stage A to C. There was significant difference between stage A and B. Cutoff value for detecting stage B HF was 19.73 ng/ml for catestatin with 90% sensitivity and 50.9% specificity. These results may have implications in the new method to detect patients with stage B HF. PMID- 22050389 TI - Polymorphism and a metastable solvate of duloxetine hydrochloride. AB - Duloxetine hydrochloride (1) is an important antidepressant that acts as a serotonin and noradrenaline reuptake inhibitor that has only recently been characterized by single-crystal X-ray diffraction. This study describes an investigation into polymorphism of duloxetine hydrochloride, discusses the challenges of characterizing new structures, and reports a new metastable solvate (1(acetone)) where acetone is trapped in a duloxetine hydrochloride host lattice. In view of the importance of formulation processing and bioavailability characteristics of the crystalline forms of 1, a comprehensive structural study of 1(acetone) was carried out using single-crystal and powder X-ray diffraction, infrared and Raman spectroscopies, and solid-state NMR spectroscopy. The rapid desolvation from 1(acetone) to the stable unsolvated form was investigated, and the structures of free and solvated forms are discussed in terms of the noncovalent intermolecular interactions. PMID- 22050390 TI - Decision analysis and risk models for land development affecting infrastructure systems. AB - Coordination and layering of models to identify risks in complex systems such as large-scale infrastructure of energy, water, and transportation is of current interest across application domains. Such infrastructures are increasingly vulnerable to adjacent commercial and residential land development. Land development can compromise the performance of essential infrastructure systems and increase the costs of maintaining or increasing performance. A risk-informed approach to this topic would be useful to avoid surprise, regret, and the need for costly remedies. This article develops a layering and coordination of models for risk management of land development affecting infrastructure systems. The layers are: system identification, expert elicitation, predictive modeling, comparison of investment alternatives, and implications of current decisions for future options. The modeling layers share a focus on observable factors that most contribute to volatility of land development and land use. The relevant data and expert evidence include current and forecasted growth in population and employment, conservation and preservation rules, land topography and geometries, real estate assessments, market and economic conditions, and other factors. The approach integrates to a decision framework of strategic considerations based on assessing risk, cost, and opportunity in order to prioritize needs and potential remedies that mitigate impacts of land development to the infrastructure systems. The approach is demonstrated for a 5,700-mile multimodal transportation system adjacent to 60,000 tracts of potential land development. PMID- 22050391 TI - Glycemic control and hypoglycemia in Veterans Health Administration patients converted from glyburide to glipizide. AB - BACKGROUND: In 2009, the Veterans Health Administration (VHA) released a national bulletin regarding the risk of hypoglycemia associated with the use of glyburide in elderly patients with renal dysfunction. Providers were encouraged to avoid glyburide and use glipizide in patients with a calculated creatinine clearance (CrCl) of less than 50 mL per minute. Since this initiative, many veterans were converted by their providers from glyburide to glipizide regardless of renal impairment. OBJECTIVES: To (a) identify whether hemoglobin A1c remained equivalent in patients converted from glyburide to glipizide, (b) evaluate the prevalence of hypoglycemia during treatment with glyburide or glipizide, (c) compare change in glycemic control for renally impaired versus nonimpaired patients, and (d) analyze dosage conversion ratios selected by providers and measures of patient follow-up after conversion including time until A1c measurement and number of glipizide dose titrations. METHODS: This was a single center, retrospective analysis of veterans converted from glyburide to glipizide from January 1, 2008, through May 31, 2010, who had documented A1c values concurrent with glyburide and glipizide use. A 2-sided equivalence analysis was used for the primary outcome. Equivalence was defined as a change in mean A1c of +/- 0.2. Hypoglycemia was defined as blood glucose of less than 70 mg per dL, symptoms of hypoglycemia, or hypoglycemia that led to a fall, loss of consciousness, emergency room visit, hospitalization, or death. The pre- to post conversion change in rates of hypoglycemia was tested for significance using a McNemar's test. RESULTS: In the 141 (99.3% male, 53.9% CrCl less than 50 mL per minute, mean age = 74.0 years) patients meeting inclusion criteria between 2008 2010, the average change in A1c (+ 0.34) was nonequivalent after conversion from glyburide to glipizide (7.08% vs. 7.42%, respectively). Hypoglycemia occurred more frequently during treatment with glyburide than glipizide (31.2% vs. 12.8%, respectively, P less than 0.001). Mean dose conversion ratios were consistent with VHA recommendations (1 mg per day glyburide = 1.26- 1.55 mg per day glipizide). CONCLUSIONS: Conversion from glyburide to glipizide was associated with an increase in A1c, but the incidence of hypoglycemia was reduced. Results of this study are consistent with the recommendation of the American Diabetes Association and European Association for the Study of Diabetes to use second generation sulfonylureas other than glyburide. Patients converted to glipizide should be monitored closely to adjust therapy as appropriate to maintain glycemic control. PMID- 22050392 TI - All-cause and bleeding-related health care costs in warfarin-treated patients with atrial fibrillation. AB - BACKGROUND: Bleeding is a major complication of warfarin therapy. Assessing the cost of warfarin-associated bleeding may more fully describe the costs associated with warfarin use. OBJECTIVE: To assess health care costs related to warfarin associated bleeding in patients with newly diagnosed atrial fibrillation (AF). METHODS: Medical and pharmacy claims were analyzed for patients with AF (ICD-9-CM code 427.31) in the Medstat MarketScan database from January 2003 to December 2007. Eligible patients had no warfarin pharmacy claim or AF diagnosis in the 4 months prior to AF index date, a warfarin pharmacy claim within 30 days of AF diagnosis, and 12 months follow-up data after the index warfarin claim. Subjects were categorized based on the first type of bleeding event observed during follow up, and only bleeding events occurring within 30 days following a warfarin claim were considered. Intracranial hemorrhage (ICH) and gastrointestinal (GI) events were assessed based on primary or secondary ICD-9-CM codes, and major GI bleeding was defined as a GI bleed associated with hospitalization. Annual total all-cause allowed charges in patients with and without bleeding events after the index warfarin claim were compared using generalized linear model (GLM) regression with gamma distribution and log link, controlling for demographics, insurance status, and comorbidities. Costs for claims with a primary or secondary diagnosis of bleeding were calculated separately. RESULTS: Of the 47,437 patients who were analyzed, 194 (0.4%) had an ICH, 919 (1.9%) had a major GI bleed, and 1,804 (3.8%) had a minor GI bleed within 30 days after a warfarin claim during follow up. Compared with patients who had no bleeding events after a warfarin claim (n = 44,520, 93.9%) during the study period, patients with at least 1 bleeding event were older and had more comorbidities (P < 0.01). Patients with at least 1 ICH or major GI bleed had more all-cause hospitalizations (P < 0.05) and hospital days (P < 0.01) than patients without bleeding events. Patients with at least 1 ICH, major GI bleed, or minor GI bleed had more all-cause emergency room visits (P < 0.01) than patients without bleeding events. Mean (SD) unadjusted all-cause health care costs in the 12 months after the warfarin index claim were $41,903 ($56,654), $40,586 ($65,164), and $24,347 ($56,488) for patients with at least 1 ICH, major GI bleed, and minor GI bleed, respectively, compared with $24,129 ($36,425) for patients with no bleeding events. Claims with a primary or secondary diagnosis of bleeding accounted for 49.6%, 30.2%, and 2.6% of annual cost in patients with ICH, major GI bleeding, and minor GI bleeding, respectively. On average, 50.9%, 33.5%, and 10.8% of annual all-cause costs occurred within 30 days after the first ICH, major GI bleeding event, and minor GI bleeding event, respectively. GLM regression showed that annual all-cause costs were 64.4% and 49.0% higher (P? less than ?0.001) for patients with ICH and major GI bleeding, respectively, than for patients with no bleeding events. CONCLUSION: ICH and major GI bleeding associated with warfarin therapy are rare but costly. PMID- 22050393 TI - Formulary management of the protease inhibitors boceprevir and telaprevir for chronic hepatitis C virus. AB - BACKGROUND: Hepatitis C virus (HCV) is the most common chronic bloodborne illness in the United States. The incidence of acute hepatitis C in the United States peaked near 50,000 cases in the late 1980s but has stabilized since 2003 to less than 5,000 cases annually. The combination of pegylated interferon (peginterferon) and ribavirin has been the standard recommended treatment for HCV. Protease inhibitors telaprevir and boceprevir were approved by the FDA in May 2011 for the treatment of hepatitis C genotype 1 in combination with peginterferon and ribavirin. OBJECTIVE: To review the phase 3 trials for telaprevir and boceprevir and provide managed care considerations. METHODS: A MEDLINE review was performed for articles published and available through September 15, 2011, using keywords "boceprevir" or "telaprevir" with an emphasis on phase 3 trials. The literature search was limited to articles in English, clinical trials, randomized controlled trials, and research conducted in humans. Additional information was obtained from the FDA website. RESULTS: Three phase 3 trials are available for telaprevir, which provided data that were the basis for FDA approval. Boceprevir demonstrated efficacy and safety in 2 pivotal phase 3 trials. Both agents demonstrated statistically significantly higher rates of virologic response compared with the standard of care involving peginterferons and ribavirin. Telaprevir and boceprevir also demonstrated efficacy in the treatment of patients who had previously failed dual therapy for hepatitis C. Safety concerns for both agents include anemia, drug interactions, skin rashes, and gastrointestinal adverse events. CONCLUSIONS: Decision makers have many factors to consider in developing a strategy around hepatitis C. Increased drug costs, patient management, adherence, comparative safety and efficacy, and appropriate utilization management controls are important issues. Payers may consider developing clinical programs to encourage adherence and appropriate use and leverage an appropriate channel to ensure cost-effective therapy. PMID- 22050394 TI - Assessment of the appropriateness of serum digoxin concentration measurement in a medical group setting. AB - BACKGROUND: Recent quality initiatives require that the routine annual therapeutic drug-monitoring (TDM) parameters for the high-risk medication digoxin include a measure of renal function and a serum potassium level but not a serum digoxin concentration (SDC) measurement. Several studies have shown that the majority of the SDCs obtained in hospital settings provide little clinically actionable information. OBJECTIVE: To evaluate the appropriateness and utility of SDCs ordered in a medical group practice setting by categorizing the reason the SDC was ordered and identifying action taken in response to the result. METHODS: The descriptive study was conducted as a retrospective, electronic medical record (EMR) review of 90 primary care patients with continuous prescriptions for digoxin current on their medication profile with no gaps in therapy for at least 2 years prior to an SDC result entered into the EMR between January 1, 2009, and September 30, 2009. The reason the SDC was ordered was abstracted independently by 2 reviewers, who then assigned it to 1 of 8 predefined indication categories based on previously published criteria and practice guidelines. A third reviewer resolved inter-reviewer discrepancy (n = 1). RESULTS: A total of 90 patients with at least 1 SDC met inclusion criteria. Routine monitoring was the most frequent SDC order indication category with 35 patients (38.9%), 17 (48.6%) of whom did not have the recommended monitoring measures of potassium or renal function drawn concurrently. Patients were included in other categories as follows: confirmation of signs/symptoms of toxicity 30 (33.3%); assessment of factors altering pharmacokinetics 5 (5.6%); assessment of dosage change 5 (5.6%); assessment of drug interaction 3 (3.3%); assessment of clinical response 3 (3.3%); assessment of adherence 1 (1.1%); and other 2 (2.2%). Across all categories, a total of 19 (21.1%) of SDC results were outside the therapeutic range of 0.5 nanograms (ng) per mL and 2.0 ng per mL, 18 of which were below 0.5 ng per mL, with none of the subtherapeutic levels leading to a change in digoxin therapy. Only 1 patient (1.1%) had therapy changed in response to an elevated abnormal SDC result of 2.1 ng per mL and was in the routine monitoring category. CONCLUSIONS: The majority of SDC results obtained in our medical group setting did not lead to clinical action, such as dose adjustment or drug discontinuation. SDCs were commonly measured as part of routine monitoring, which is considered an inappropriate indication, and often without being accompanied by better markers for digoxin toxicity such as serum potassium levels and measures of renal function as recommended by drug-monitoring quality initiatives. Provider education is needed regarding the most indicative digoxin TDM parameters to obtain in order to satisfy quality initiatives. PMID- 22050395 TI - Evaluation of pneumococcal vaccination rates after vaccine protocol changes and nurse education in a tertiary care teaching hospital. AB - BACKGROUND: Pneumococcal vaccination in eligible patients is recommended by the Infectious Disease Society of America and the Centers for Disease Control (CDC) Advisory Committee on Immunization Practices. Because hospitalization provides an opportunity to vaccinate patients at high risk for developing serious pneumonia complications, eligibility screening and administration of the pneumococcal vaccine prior to discharge in qualified patients are evaluated by the Joint Commission and the Centers for Medicare Medicaid Services (CMS) as part of pneumococcal vaccination core quality measures. Among patients with an inpatient diagnosis of pneumonia in 2008, 56% in our 580-bed tertiary care teaching hospital, compared with 84% nationwide, received pneumococcal vaccination. To improve pneumococcal vaccination rates for all patients in the study facility and not just those with pneumonia, a multifaceted intervention including a revised nurse screening tool, rescheduling of the vaccine order, storage of the vaccine in automated dispensing cabinets on the nursing unit, and creation of a vaccine tracking system was developed and implemented between August 2009 and October 2009. OBJECTIVE: To determine the impact of a multifaceted intervention on pneumococcal vaccine screening and administration rates in eligible patients according to the CDC recommendations who were admitted to an internal medicine unit of a tertiary care teaching hospital. METHODS: All patients aged 18 years or older from 2 internal medicine units were identified during 4-month time intervals before (pre-intervention, April through July 2009) and after (post intervention, November 2009 through February 2010) implementation of the multifaceted pneumococcal vaccine protocol. Of these, 150 patients from each 4 month period were randomly selected for electronic medical record review. Eligibility for pneumococcal vaccination was derived from the CDC recommendations and consensus of the vaccine steering committee at the study institution; the criteria included aged 65 years or older, admitting diagnosis of pneumonia, at least 1 of several chronic diseases, immunocompromising condition, cochlear implant, cerebrospinal fluid leak, current tobacco smoking, pregnancy or having a child in the home less than aged 6 months, or awaiting solid organ transplantation. Patients who had vaccine contraindications/precautions or had been vaccinated in the previous 5 years were ineligible. Data on demographics, presence of vaccine screening, indication, administration, rescheduling, and refusal were collected. The primary endpoint was the rate of pneumococcal vaccine administration in eligible medicine patients. Secondary endpoints included changes in screening rates, vaccine refusal, and order rescheduling. Descriptive statistics and Student's t-test were used to evaluate patient demographic data. Pearson chi-square was used to compare the pre- and post-implementation periods. RESULTS: The rate of pneumococcal vaccine administration in eligible patients significantly improved post-implementation compared with pre-implementation (74.2% vs. 19.1%, respectively, P < 0.001). Rates of vaccine screening were similar pre-implementation (96.0%) and post-implementation (99.3%, P = 0.056). The rates of vaccine refusal in the pre- and post-implementation periods did not significantly differ (10.6% vs. 22.6%, respectively, P = 0.203). CONCLUSIONS: Implementation of vaccine protocol changes was associated with improved pneumococcal vaccination rates in eligible medicine patients. Protocol changes were relatively easy to implement in a large institution, and a similar approach may be implemented at other institutions as an effective way to improve pneumococcal vaccination rates. PMID- 22050396 TI - The expanding role of the pharmacist in the management of hepatitis C infection. PMID- 22050397 TI - Careful scrutiny of the evidence for drug-drug interactions in clinical decision support systems is necessary. PMID- 22050398 TI - Electronic prescription errors in an ambulatory pharmacy. PMID- 22050399 TI - Absence seizures with intellectual disability as a phenotype of the 15q13.3 microdeletion syndrome. AB - 15q13.3 microdeletions are the most common genetic findings identified in idiopathic generalized epilepsies to date, and they are present in up to 1% of patients. In addition, 15q13.3 microdeletions have been described in patients with epilepsy as part of a complex neurodevelopmental phenotype. We analyzed a cohort of 570 patients with various pediatric epilepsies for 15q13.3 microdeletions. Screening was performed using quantitative polymerase chain reaction; deletions were confirmed by array comparative genomic hybridization (CGH). We carried out detailed phenotyping of deletion carriers. In total, we identified four pediatric patients with 15q13.3 microdeletions, including one previously described patient. Two of four deletions were de novo, one deletion was inherited from an unaffected parent, and for one patient the inheritance is unknown. All four patients had absence epilepsy with various degrees of intellectual disability. We suggest that absence epilepsy accompanied by intellectual disability may represent a common phenotype of the 15q13.3 microdeletion in pediatric patients with epilepsy. PMID- 22050400 TI - Lithium aluminates on a molecular titanium oxide. AB - Lithium aluminates Li[Al(O-2,6-Me(2)C(6)H(3))R'(3)] (R' = Et, Ph) react with the MU(3)-alkylidyne oxoderivative ligands [{Ti(eta(5)-C(5)Me(5))(MU-O)}(3)(MU(3) CR)] [R = H (1), Me (2)] to afford the aluminum-lithium-titanium cubane complexes [{R'(3)Al(MU-O-2,6-Me(2)C(6)H(3))Li}(MU(3)-O)(3){Ti(eta(5)-C(5)Me(5))}(3)(MU(3) CR)] [R = H, R' = Et (5), Ph (7); R = Me, R' = Et (6), Ph (8)]. Complex 7 evolves with the formation of a lithium dicubane species and a Li{Al(MU-O-2,6 Me(2)C(6)H(3))Ph(3)}(2)] unit. PMID- 22050401 TI - Does Vitamin D deficiency play a role in peripheral neuropathy in Type 2 diabetes? AB - AIM: Despite recent reports linking vitamin D deficiency with increased risk of diabetes mellitus and complications, there is limited data on patients with diabetic peripheral neuropathy. We aimed to evaluate the incidence and associations of vitamin D deficiency in 210 patients with Type 2 diabetes with and without diabetic peripheral neuropathy. METHODS: Renal, liver, lipid profile and HbA(1c) were measured. Vitamin D status was determined by measuring 25 dihydroxyvitamin D. Presence or absence of coronary heart disease was determined and early-morning urine microalbumin:creatinine ratio was measured. All patients were assessed clinically using neuropathy symptom score, neuropathy disability score and nerve conduction study. RESULTS: Eighty-seven patients had diabetic peripheral neuropathy and these patients had significantly longer duration of diabetes and higher HbA(1c). Age, gender, incidence of retinopathy and coronary heart disease were not significantly different from those without neuropathy. Mean (SD) vitamin D was significantly lower in those with neuropathy [36.9 (39.9) nmol/l] compared with those without [58.32 (58.9) nmol/l] and 81.5% of patients with neuropathy had vitamin D deficiency compared with 60.4% of those without. Vitamin D showed significant (P < 0.05) correlations with total cholesterol, LDL cholesterol and urine microalbumin:creatinine ratio. Binary logistic regression analysis showed that diabetic peripheral neuropathy was significantly associated with vitamin D deficiency (odds ratio = 3.47; 95% CI = 1.04-11.56, P = 0.043) after inclusion of potential confounders such as duration of diabetes, HbA(1c) and LDL-cholesterol. CONCLUSION: Vitamin D deficiency is an independent risk factor for diabetic peripheral neuropathy, and further studies are required to confirm if Vitamin D supplementation could prevent or delay the onset. PMID- 22050402 TI - Nano-scaled pH-responsive polymeric vesicles for intracellular release of doxorubicin. AB - Polymeric vesicles produced by spontaneous self-association of poly(acrylic acid co-distearin acrylate) (poly(AAc-co-DSA)) with varying ratios of AAc and DSA units in aqueous solution of pH 5.0 exhibit the pH-regulated drug release behavior. Through the electrostatic interaction with ionized AAc residues, doxorubicin (DOX) molecules can be highly accommodated onto either the inner or outer surfaces of vesicles when the pH is adjusted from 5.0 to 7.4. The extent of DOX encapsulation is dependent largely on the structural transition of vesicles in response to the pH change. While the pH-evolved drug release profile varies to some extent with the distribution of DOX molecules within vesicles, the drug release from vesicles is accelerated significantly via the disruption of the electrostatic interaction of DOX species with ionized AAc moieties at pH 5.0. The DOX-loaded polymeric vesicles show promoted cellular uptake and cytotoxicity comparable to free DOX for HeLa cells. This indicates that they are probably taken up by the cells via the lipid raft-mediated endocytosis. PMID- 22050403 TI - Toxicological review and oral risk assessment of terephthalic acid (TPA) and its esters: A category approach. AB - Polyethylene terephthalate, a copolymer of terephthalic acid (TPA) or dimethyl terephthalate (DMT) with ethylene glycol, has food, beverage, and drinking water contact applications. Di-2-ethylhexyl terephthalate (DEHT) is a plasticizer in food and drinking water contact materials. Oral reference doses (RfDs) and total allowable concentrations (TACs) in drinking water were derived for TPA, DMT, and DEHT. Category RfD and TAC levels were also established for nine C(1)-C(8) terephthalate esters. The mode of action of TPA, and of DMT, which is metabolized to TPA, involves urinary acidosis, altered electrolyte elimination and hypercalciuria, urinary supersaturation with calcium terephthalate or calcium hydrogen terephthalate, and crystallization into bladder calculi. Weanling rats were more sensitive to calculus formation than dams. Calculi-induced irritation led to bladder hyperplasia and tumors in rats fed 1000 mg/kg-day TPA. The lack of effects at 142 mg/kg-day supports a threshold for urine saturation with calcium terephthalate, a key event for calculus formation. Chronic dietary DMT exposure in rodents caused kidney inflammation, but not calculi. Chronic dietary DEHT exposure caused general toxicity unrelated to calculi, although urine pH was reduced suggesting the TPA metabolite was biologically-active, but of insufficient concentration to induce calculi. Respective oral reference doses of 0.5, 0.5, and 0.2 mg/kg-day and total allowable drinking water concentrations of 3, 3, and 1 mg/L were derived for TPA, DMT, and DEHT. An oral RfD of 0.2 mg/kg day for the terephthalate category chemicals corresponded to a drinking water TAC of 1 mg/L. PMID- 22050404 TI - Proteomic study of the impact of Hik33 mutation in Synechocystis sp. PCC 6803 under normal and salt stress conditions. AB - Cyanobacteria are the only prokaryotes possessing plasma, thylakoid, and outer membranes. The plasma membrane of a cyanobacterial cell is essential for the biogenesis of cyanobacterial photosystems and serves as a barrier against environmental stress. We previously identified dozens of salt-responsive proteins in the plasma membrane of Synechocystis sp. PCC 6803. Five histidine kinases (Hiks) including Hik33 were also proposed to be involved in the perception of salt stress in Synechocystis. In this study, we analyzed proteomic profiles of the plasma membrane from a hik33-knockout mutant (DeltaHik33) under normal and salt-stress conditions. Using 2D-DIGE followed by mass spectrometry analysis, we identified 26 differentially expressed proteins in DeltaHik33 mutant cells. Major changes, due to the Hik33 mutation, included the substrate-binding proteins of ABC transporters, such as GgtB and FutA1, regulatory proteins including MorR and Rre13, as well as several hypothetical proteins. Under salt-stress conditions, the Hik33 mutation reduced levels of 7 additional proteins, such as NrtA, nitrate/sulfonate/bicarbonate-binding protein and LexA, and enhanced levels of 9 additional proteins including SphX. These observations suggest a substantial rearrangement in the plasma membrane proteome of Synechocystis due to the loss of hik33. Furthermore, a comprehensive molecular network was revealed in DeltaHik33 mutant coping with salt stress. PMID- 22050405 TI - Life-threatening anaphylaxis to leuprorelin acetate depot: case report and review of the literature. AB - Gonadotropin-releasing hormone analog depots have been widely used for a variety of diseases including prostate cancer, breast cancer, endometriosis, uterine leiomyomas, and central precocious puberty. Most of the side/adverse effects of gonadotropin-releasing hormone analog depots, such as leuprorelin acetate depot, are related to hypotestosteronism in males. Anaphylaxis to gonadotropin-releasing hormone analog depot is extremely rare. We present the first case report of a Japanese man who developed anaphylaxis to leuprorelin acetate depot during the treatment of metastatic prostate cancer and recovered successfully by conservative treatment. A drug-lymphocyte stimulation test showed that not only leuprorelin acetate itself, but also its vehicle polylactic and glycolic acids, might be responsible for the anaphylaxis to leuprorelin acetate depot. Because anaphylaxis can be lethal, the present case suggests that one should bear in mind the possibility of anaphylaxis in all patients who receive gonadotropin-releasing hormone analog depot and monitor such patients carefully. PMID- 22050406 TI - Variations in immunohistochemical preservation of proteins in a mummification model. AB - Immunohistochemistry is an important tool in the investigation of ancient mummified remains because of its ability not only to detect proteins but also to isolate their location to specific tissues and thereby improve confidence that the results are genuine. A mouse model of Egyptian mummification has been used to demonstrate that the survival of proteins, judged by the retention of immunohistochemical staining, varies markedly. Some survive the process well, whereas others become barely detectable despite the morphology of the tissue being excellently preserved. The results obtained show that protein preservation is multi-factorial, with tissue type and degradation, and the properties of the protein itself all having significant effects. Proteins forming large, multi subunit complexes such as collagen IV appear to be more resistant to degradation than those that do not, such as S-100. Although modern modelling studies cannot replicate the full extent of degradative processes and taphonomic changes experienced by real mummies, the results obtained can be useful for guiding research that requires ancient tissues. PMID- 22050407 TI - The effect of adolescent- and parent-induced family transitions in middle adolescence. AB - In a longitudinal school-based survey of Finnish adolescents aged 15-16 years at baseline, we examined associations of parent-induced family transitions (parental separation, divorce, remarriage) and adolescent-induced family transitions (moving away from the parental home) with adolescent maladjustment (substance abuse and internalizing symptoms). The findings revealed that externalizing problems were associated with moving away from the parental home, whereas the risk of internalizing problems was associated with a change in the caretaking parent through parental marital transition or being taken into custody. PMID- 22050408 TI - Ultrastable, redispersible, small, and highly organomodified mesoporous silica nanotherapeutics. AB - Practical biomedical application of mesoporous silica nanoparticles is limited by poor particle dispersity and stability due to serious irreversible aggregation in biological media. To solve this problem, hydrothermally treated mesoporous silica nanoparticles of small size with dual-organosilane (hydrophilic and hydrophobic silane) surface modification have been synthesized. These highly organomodified mesoporous silica nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, N(2) adsorption-desorption, dynamic light scattering, zeta potential, and solid-state (29)Si NMR, and they prove to be very stable in simulated body fluid at physiological temperature. Additionally, they can be dried to a powdered solid and easily redispersed in biological media, maintaining their small size for a period of at least 15 days. Furthermore, this preparation method can be expanded to synthesize redispersible fluorescent and magnetic mesoporous silica nanoparticles. The highly stable and redispersible mesoporous silica NPs show minimal toxicity during in vitro cellular assays. Most importantly, two types of doxorubicin, water-soluble doxorubicin and poorly water soluble doxorubicin, can be loaded into these highly stable mesoporous silica nanoparticles, and these drug-loaded nanoparticles can also be well-redispersed in aqueous solution. Enhanced cytotoxicity to cervical cancer (HeLa) cells was found upon treatment with water-soluble doxorubicin-loaded nanoparticles compared to free water-soluble doxorubicin. These results suggest that highly stable, redispersible, and small mesoporous silica nanoparticles are promising agents for in vivo biomedical applications. PMID- 22050409 TI - Injury incidence and patterns in workers with intellectual disability: a comparative study. AB - BACKGROUND: Workplace safety is a concern in the employment of persons with intellectual disability, due to both real concerns for employee well-being, and the effect that negative perceptions of safety risk can have on hiring. METHOD: This study involved a retrospective analysis of workplace insurance claim records for workers with and without disability in a Canadian social enterprise. RESULTS: Workers with intellectual disability sustained fewer injuries and experienced fewer absences due to injury than workers without disability. Lost-time injury rates for this business were not significantly different from those reported by other employers in the jurisdiction. CONCLUSION: Workplace safety is a concern for all workers, but fear of increased injury rates and heightened compensation costs should not be perceived as a risk when hiring individuals with intellectual disability. PMID- 22050410 TI - Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers. AB - There are limited data concerning the effects of 5-HT(1A) receptor activation on esophageal motility. Sumatriptan, a 5-HT(1A) receptor agonist, was recently reported to enhance esophageal peristalsis after intravenous administration. Buspirone, an orally available 5-HT(1A) receptor agonist, was shown to modulate gastroduodenal motor function. Our aim was to evaluate the effect of buspirone on esophageal motility of healthy volunteers. On two separate visits, 20 healthy volunteers aged 21-29 years (nine women) underwent esophageal manometry before and 10, 30, and 60 minutes after the administration of buspirone 20-mg or placebo capsule, according to a double-blind crossover design. At each time point, we compared buspirone and placebo effects on: resting pressure of the lower esophageal sphincter (LES); residual pressure and duration of LES relaxation; amplitude, duration, and onset velocity of esophageal body contractions, during 10 swallows of 5 mL of water. Significant analysis of variance differences (P < 0.05) are presented as mean +/- standard deviation. Buspirone significantly increased mean distal esophageal wave amplitude (151 vs. 87 mmHg, P < 0.05) and duration (6.1 vs. 4.2 seconds, P < 0.05). Similarly, buspirone significantly increased mean LES resting pressure (26 vs. 21 mmHg, P < 0.05) and mean residual LES pressure (7.9 vs. 2 mmHg, P < 0.05), whereas reduced mean LES relaxation duration (7.2 vs. 8.0 seconds, P < 0.05) and mean distal onset velocity (7.6 vs. 14.7 cm/second, P < 0.05). Buspirone enhances esophageal peristalsis and LES function in healthy volunteers. Further study is warranted on the effects of buspirone on esophageal function and symptoms in patients with ineffective esophageal motility. PMID- 22050412 TI - Taking Responsibility. PMID- 22050411 TI - Autologous haematopoietic stem cell transplantation in multiple myeloma patients from ethnic minority groups in an equal access healthcare system. PMID- 22050413 TI - Academy of Operative Dentistry Hollenback Memorial Prize. PMID- 22050414 TI - Academy of Operative Dentistry Award of Excellence. PMID- 22050419 TI - Glucocorticoid resistance in paediatric acute lymphoblastic leukaemia. AB - Glucocorticoids (GCs), such as prednisolone and dexamethasone, are key components in multi-agent chemotherapy protocols used for the treatment of acute lymphoblastic leukaemia (ALL). Approximately 10% of children with ALL will respond poorly to GCs, and GC resistance is associated with a significantly inferior outcome. This review summarises the current knowledge of GC resistance in ALL, including the roles of the GC receptor and its co-chaperone molecules, the pro-apoptotic and pro-survival B-cell lymphoma 2 family members and alternative non-apoptotic mechanisms of cell death. It concludes with a discussion on therapeutic attempts to overcome GC resistance. PMID- 22050417 TI - Morphofunctional changes underlying intestinal dysmotility in diabetic RIP I/hIFNbeta transgenic mice. AB - The pathogenetic mechanisms underlying gastrointestinal dysmotility in diabetic patients remain poorly understood, although enteric neuropathy, damage to interstitial cells of Cajal (ICC) and smooth muscle cell injury are believed to play a role. The aim of this study was to investigate the morphological and functional changes underlying intestinal dysmotility in RIP-I/hIFNbeta transgenic mice treated with multiple very low doses of streptozotocin (20 mg/kg, i.p., 5 days). Compared with vehicle-treated mice, streptozotocin-treated animals developed type 1 diabetes mellitus, with sustained hyperglycaemia for 3.5 months, polyphagia, polydipsia and increased faecal output without changes in faecal water content (metabolic cages). Diabetic mice had a longer intestine, longer ileal villi and wider colonic crypts (conventional microscopy) and displayed faster gastric emptying and intestinal transit. Contractility studies showed selective impaired neurotransmission in the ileum and mid-colon of diabetic mice. Compared with controls, the ileal and colonic myenteric plexus of diabetic mice revealed ultrastructural features of neuronal degeneration and HuD immunohistochemistry on whole-mount preparations showed 15% reduction in neuronal numbers. However, no immunohistochemical changes in apoptosis-related markers were noted. Lower absolute numbers of neuronal nitric oxide synthase- and choline acetyltransferase-immunopositive neurons and enhanced vasoactive intestinal polypeptide and substance P immunopositivity were observed. Ultrastructural and immunohistochemical analyses did not reveal changes in the enteric glial or ICC networks. In conclusion, this model of diabetic enteropathy shows enhanced intestinal transit associated with intestinal remodelling, including neuroplastic changes, and overt myenteric neuropathy. Such abnormalities are likely to reflect neuroadaptive and neuropathological changes occurring in this diabetic model. PMID- 22050420 TI - The erythropoietin-derived peptide mimetic pHBSP affects cellular and cognitive consequences in a rat post-status epilepticus model. AB - PURPOSE: The selection of a minimal active sequence of erythropoietin allowed the design of peptide mimetics that exert beneficial effects in the central nervous system but lack an erythropoietic effect. Erythropoietin has been suggested as a promising therapeutic and prophylactic for epilepsies based on its neuroprotective, neuroregenerative, and antiinflammatory potency. Therefore, it is of particular interest to evaluate whether the nonerythropoietic erythropoietin-derived peptide pHBSP can affect epileptogenesis. METHODS: In a post-status epilepticus model in rats, we determined the effects of pHBSP and of recombinant human erythropoietin with short-term administration following status epilepticus. KEY FINDINGS: Both pHBSP and erythropoietin further enhanced the status epilepticus-associated increase in hippocampal cell proliferation. Thereby, pHBSP seemed to promote neuronal differentiation and survival resulting in a significant increase in neurogenesis. Neither pHBSP nor erythropoietin affected the number of animals exhibiting spontaneous recurrent seizures as well as the seizure frequency in the chronic phase. In the Morris water maze, pHBSP attenuated cognitive deficits in epileptic animals. SIGNIFICANCE: In conclusion, the helix B-derived erythropoietin peptide pHBSP can modulate the cellular and cognitive consequences of a status epilepticus. The impact of pHBSP on spatial learning might indicate that the peptide allows beneficial effects on epileptogenesis-associated cognitive deficits. However, it needs to be considered that learning deficits were not abolished by pHBSP and that the effects were not observed consistently until the end of the study. Therefore, adjustment of timing, duration, and dose of peptide administration might be necessary to further evaluate the efficacy of pHBSP. PMID- 22050421 TI - Communicating food risks in an era of growing public distrust: three case studies. AB - The communication and regulation of risk has changed significantly over the past 30 years in Europe and to a noticeable but lesser extent in the United States. In Europe, this is partly due to a series of regulatory mishaps, ranging from mad cow disease in the United Kingdom to contamination of the blood supply in France. In the United States, general public confidence in the American government has been gradually declining for more than three decades, driven by a mix of cultural and political conflicts like negative political advertising, a corrosive news media, and cuts in regulatory budgets. While the former approach is based on an objective assessment of the risk, the latter is driven more by the perception of the risk, consumer sentiment, political will, and sectoral advocacy. In this article, the author examines three U.S.-based food case studies (acrylamide, bisphenol A, and artificial food colorings) where regulations at the local and state levels are increasingly being based on perceived risk advocacy rather than on the most effective response to the risk, be it to food safety or public health, as defined by regulatory interpretation of existing data. In the final section, the author puts forward a series of recommendations for how U.S.-based regulators can best handle those situations where the perceived risk is markedly different from the fact-based risk, such as strengthening the communication departments of food regulatory agencies, training officials in risk communication, and working more proactively with neutral third-party experts. PMID- 22050422 TI - Improvement of 2D-PAGE resolution of human, porcine and canine follicular fluid: comparison of two immunodepletion columns. AB - Follicular fluid provides the microenvironment within which somatic cells proliferate and differentiate, and the oocyte matures. It contains a number of soluble factors implicated in various stages of follicular development, most of them being functionally unknown. The presence of several high-abundance proteins, mainly originating from the blood circulation, is a major challenge of follicular fluid proteomic analysis, as these proteins can mask or decrease the visualization of follicle-specific proteins. In this study, we evaluated the efficiency of two immunodepletion columns (ProteomeLabTM IgY-HSA and MARS-6) on follicular fluids of human, porcine and canine prior to 2D-PAGE. Our results showed that both columns were suitable to remove some of the high-abundance proteins present in human and canine follicular fluid. In conclusion, we demonstrated that the immunodepletion strategy enables the detection of new protein spots, increases resolution and highly improves the intensity of low abundance proteins by 2D-PAGE. PMID- 22050423 TI - Nicotine: specific role in angiogenesis, proliferation and apoptosis. AB - Nowadays, tobacco smoking is the cause of ~5-6 million deaths per year, counting 31% and 6% of all cancer deaths (affecting 18 different organs) in middle-aged men and women, respectively. Nicotine is the addictive component of tobacco acting on neuronal nicotinic receptors (nAChR). Functional nAChR, are also present on endothelial, haematological and epithelial cells. Although nicotine itself is regularly not referred to as a carcinogen, there is an ongoing debate whether nicotine functions as a 'tumour promoter'. Nicotine, with its specific binding to nAChR, deregulates essential biological processes like regulation of cell proliferation, apoptosis, migration, invasion, angiogenesis, inflammation and cell-mediated immunity in a wide variety of cells including foetal (regulation of development), embryonic and adult stem cells, adult tissues as well as cancer cells. Nicotine seems involved in fundamental aspects of the biology of malignant diseases, as well as of neurodegeneration. Investigating the biological effects of nicotine may provide new tools for therapeutic interventions and for the understanding of neurodegenerative diseases and tumour biology. PMID- 22050425 TI - Extended versus limited lymph node dissection in radical cystectomy: impact on recurrence pattern and survival. AB - OBJECTIVES: To compare recurrence patterns and survival of patients with carcinoma of the urinary bladder undergoing radical cystectomy and extended or limited lymph node dissection. METHODS: From a consecutive series of 469 patients undergoing radical cystectomy, two different historical cohorts were constructed; one with 265 patients intentionally undergoing extended lymph node dissection and one with 204 patients undergoing limited lymph node dissection. RESULTS: Early lymph node recurrences were more frequently located outside the pelvic region in patients from the extended lymph node dissection cohort, whereas the overall risk of recurrence was not reduced by carrying out an extended lymph node dissection compared with the limited lymph node dissection cohort (8% vs 6%, P = 0.5). However, positive node patients had a significantly better prognosis after extended lymph node dissection (5-year disease-specific survival 29% vs 8%, P = 0.002). Improved survival was also found in negative node patients with non-organ confined tumors undergoing extended lymph node dissection compared with limited lymph node dissection (5-year disease-specific survival 76% vs 62%, P = 0.008). A total of 16 positive node patients (6%) in the extended lymph node dissection cohort were identified as possible stage migrators with metastasis exclusively in lymph nodes outside the limited template. A total of 5% of patients undergoing extended lymph node dissection had an evident survival benefit of an extended lymph node dissection compared with a limited lymph node dissection. CONCLUSIONS: Extended lymph node dissection provides more accurate nodal staging than a limited lymph node dissection. However, recurrence patterns are not significantly altered by extending the limits of lymph node dissection, suggesting a survival benefit only in a minority of patients. Improved survival is more likely in patients with locally advanced disease. PMID- 22050424 TI - Proteomic analysis of early-responsive redox-sensitive proteins in Arabidopsis. AB - Regulation of protein function through oxidative modification has emerged as an important molecular mechanism modulating various biological processes. Here, we report a proteomic study of redox-sensitive proteins in Arabidopsis cells subjected to H(2)O(2) treatment. Four gel-based approaches were employed, leading to the identification of four partially overlapping sets of proteins whose thiols underwent oxidative modification in the H(2)O(2)-treated cells. Using a method based on differential labeling of thiols followed by immunoprecipitation and Western blotting, five of the six selected putative redox-sensitive proteins were confirmed to undergo oxidative modification following the oxidant treatment in Arabidopsis leaves. Another method, which is based on differential labeling of thiols coupled with protein electrophoretic mobility shift assay, was adopted to reveal that one of the H(2)O(2)-sensitive proteins, a homologue of cytokine induced apoptosis inhibitor 1 (AtCIAPIN1), also underwent oxidative modification in Arabidopsis leaves after treatments with salicylic acid or the peptide elicitor flg22, two inducers of defense signaling. The redox-sensitive proteins identified from the proteomic study are involved in various biological processes such as metabolism, the antioxidant system, protein biosynthesis and processing, and cytoskeleton organization. The identification of novel redox-sensitive proteins will be helpful toward understanding of cellular components or pathways previously unknown to be redox-regulated. PMID- 22050427 TI - Combinatorial atmospheric pressure chemical vapor deposition (cAPCVD): a route to functional property optimization. AB - We demonstrate how combinatorial atmospheric pressure chemical vapor deposition (cAPCVD) can be used as a synthetic tool for rapidly optimizing the functional properties of thin-films, by analyzing the self-cleaning properties of tungsten doped anatase as an example. By introducing reagents at separate points inside the reactor, a tungsten/titanium compositional gradient was formed and a diverse range of film growth conditions were obtained. By partially mixing the metal sources, a combinatorial film with a compositional profile that varied primarily in the lateral plane was synthesized. A combinatorial thin-film of anatase TiO(2) doped with an array of tungsten levels as a solid solution ranging from 0.38-13.8 W/Ti atom % was formed on a single glass substrate. The compositional-functional relationships were understood through comprehensively analyzing combinatorial phase space, with 200 positions investigated by high-throughput methods in this study. Physical and functional properties, and their compositional dependencies, were intercorrelated. It was found that increases in photocatalytic activity and conductivity were most highly dependent on film crystallinity within the 0.38 13.8 atom % W/Ti doping regime. However, enhancements in photoinduced surface wetting were primarily dependent on increases in preferred growth in the (211) crystal plane. PMID- 22050428 TI - Death rate of residents with diabetes in nursing homes. PMID- 22050430 TI - Validating a firefly luciferase-based high-throughput screening assay for antimalarial drug discovery. AB - The emergence and spread of multidrug-resistant Plasmodium falciparum and recent detection of potential artemisinin-resistant strains in Southeast Asia highlight the importance of developing novel antimalarial therapies. Using a previously generated stable transgenic P. falciparum line with high-level firefly luciferase expression, we report the adaptation, miniaturization, optimization, and validation of a high-throughput screening assay in 384-well plates. Assay conditions, including the percentage of parasitemia and hematocrit, were optimized. Parameters of assay robustness, including Z'-value, coefficient variation (CV), and signal-to-background (S/B) ratio, were determined. The LOPAC(1280) small-compound library was used to validate this assay. Our results demonstrated that this assay is robust and reliable, with an average Z'-value of >0.7 and CV of <10%. Moreover, this assay showed a very low background, with the S/B ratio up to 71. Further, identified hits were selected and confirmed using a SYBR Green I-based confirmatory assay. It is evident that this assay is suitable for large-scale screening of chemical libraries for antimalarial drug discovery. PMID- 22050432 TI - Theory of mind in schizophrenia: exploring neural mechanisms of belief attribution. AB - BACKGROUND: Although previous behavioral studies have shown that schizophrenia patients have impaired theory of mind (ToM), the neural mechanisms associated with this impairment are poorly understood. This study aimed to identify the neural mechanisms of ToM in schizophrenia, using functional magnetic resonance imaging (fMRI) with a belief attribution task. METHODS: In the scanner, 12 schizophrenia patients and 13 healthy control subjects performed the belief attribution task with three conditions: a false belief condition, a false photograph condition, and a simple reading condition. RESULTS: For the false belief versus simple reading conditions, schizophrenia patients showed reduced neural activation in areas including the temporoparietal junction (TPJ) and medial prefrontal cortex (MPFC) compared with controls. Further, during the false belief versus false photograph conditions, we observed increased activations in the TPJ and the MPFC in healthy controls, but not in schizophrenia patients. For the false photograph versus simple reading condition, both groups showed comparable neural activations. CONCLUSIONS: Schizophrenia patients showed reduced task-related activation in the TPJ and the MPFC during the false belief condition compared with controls, but not for the false photograph condition. This pattern suggests that reduced activation in these regions is associated with, and specific to, impaired ToM in schizophrenia. PMID- 22050434 TI - A novel model of accelerated intimal hyperplasia in the pig iliac artery. AB - There is no good animal model of large artery injury-induced intimal hyperplasia (IH). Those available are reproducible, providing only a few layers of proliferating cells or have the disadvantage of the presence of a metallic stent that complicates histology evaluation. This study was designed to develop a new, simple model of accelerated IH based on balloon injury in conjunction with disruption of the Internal Elastic Lamina (IEL) in pig external iliac arteries. Iliac artery injury (n = 24) was performed in 12 Yorkshire pigs divided in two groups: Group I (n = 10), overdistention injury induced by an oversized non compliant balloon; Group II (n = 14), arterial wall disruption by pulling back an isometric cutting balloon (CB) followed by stretching with a compliant Fogarty Balloon (FB). At two weeks, arteries were processed for morphometric analysis and immunohistochemistry (IHC) for smooth muscle cells (SMC) and proliferating cell nuclear antigen (PCNA). When comparing the two groups, at 2 weeks, arteries of group II had a higher incidence of IH (100%vs. 50%, P = 0.0059), increased intimal areas (2.54 +/- 0.33 mm(2) vs. 0.93 +/- 0.36 mm(2) , P = 0.004), increased intimal area/Media area ratios (0.95 +/- 0.1 vs. 0.28 +/- 0.05; P < 0.0001) and decreased lumen areas (6.24 +/- 0.44 vs. 9.48 +/- 1.56, P = 0.026). No thrombosis was noticed in Group II. Neointima was composed by proliferating SMC located with the highest concentration in the area of IEL disruption (IHC). Arterial injury by pulling back CB and FB induces significant IH in pig iliac arteries by two weeks without thrombosis. This model is superior to the classical overdistention non-compliant model and should be useful and cost-effective for preclinical testing of procedures designed to inhibit IH in large peripheral arteries. PMID- 22050436 TI - Correction. PMID- 22050437 TI - Operative Dentistry Home Page. PMID- 22050440 TI - Assessing the conceptual clarity and evidence base of quality criteria/standards developed for evaluating decision aids. AB - CONTEXT: Promoting patient participation in treatment decision making is of increasing interest to researchers, clinicians and policy makers. Decision aids (DAs) are advocated as one way to help achieve this goal. Despite their proliferation, there has been little agreement on criteria or standards for evaluating these tools. To fill this gap, an international collaboration of researchers and others interested in the development, content and quality of DAs have worked over the past several years to develop a checklist and, based on this checklist, an instrument for determining whether any given DA meets a defined set of quality criteria. OBJECTIVE/METHODS: In this paper, we offer a framework for assessing the conceptual clarity and evidence base used to support the development of quality criteria/standards for evaluating DAs. We then apply this framework to assess the conceptual clarity and evidence base underlying the International Patient Decision Aids Standards (IPDAS) checklist criteria for one of the checklist domains: how best to present in DAs probability information to patients on treatment benefits and risks. CONCLUSION: We found that some of the central concepts underlying the presenting probabilities domain were not defined. We also found gaps in the empirical evidence and theoretical support for this domain and criteria within this domain. Finally, we offer suggestions for steps that should be undertaken for further development and refinement of quality standards for DAs in the future. PMID- 22050439 TI - Inhibition of NADPH oxidase promotes alternative and anti-inflammatory microglial activation during neuroinflammation. AB - Like macrophages, microglia are functionally polarized into different phenotypic activation states, referred as classical and alternative. The balance of the two phenotypes may be critical to ensure proper brain homeostasis, and may be altered in brain pathological states, such as Alzheimer's disease. We investigated the role of NADPH oxidase in microglial activation state using p47(phox) and gp91(phox) -deficient mice as well as apocynin, a NADPH oxidase inhibitor during neuroinflammation induced by an intracerebroventricular injection of LPS or Abeta1-42. We showed that NADPH oxidase plays a critical role in the modulation of microglial phenotype and subsequent inflammatory response. We demonstrated that inhibition of NADPH oxidase or gene deletion of its functional p47(phox) subunit switched microglial activation from a classical to an alternative state in response to an inflammatory challenge. Moreover, we showed a shift in redox state towards an oxidized milieu and that subpopulations of microglia retain their detrimental phenotype in Alzheimer's disease brains. Microglia can change their activation phenotype depending on NADPH oxidase-dependent redox state of microenvironment. Inhibition of NADPH oxidase represents a promising neuroprotective approach to reduce oxidative stress and modulate microglial phenotype towards an alternative state. PMID- 22050441 TI - Attitudes and beliefs about anti-retroviral therapy are associated with high risk sexual behaviors among the general population of Kisumu, Kenya. AB - Attitudes and beliefs about antiretroviral therapy (ART) may affect sexual risk behaviors among the general population in sub-Saharan Africa. We performed a cross-sectional population-based study in Kisumu, Kenya to test this hypothesis in October 2006. A total of 1655 participants were interviewed regarding attitudes and beliefs about ART and their sexual risk behaviors. The majority of participants, (71%) men and (70%) women, had heard of ART. Of these, 20% of men and 29% of women believed ART cures HIV. Among women, an attitude that "HIV is more controllable now that ART is available" was associated with sex with a non spousal partner, increased lifetime number of sexual partners as well as a younger age at sexual debut. No significant associations with this factor were found among men. The belief that "ART cures HIV" was associated with younger age of sexual debut among women. The same belief was associated with an increased likelihood of exchanging sex for money/gifts and decreased likelihood of condom use at last sex among men. These findings were most significant for people aged 15-29 years. In high HIV seroprevalence populations with expanding access to ART, prevention programs must ensure their content counteracts misconceptions of ART in order to reduce high risk sexual behaviors, especially among youth. PMID- 22050442 TI - Predicting psychological ripple effects: the role of cultural identity, in group/out-group identification, and attributions of blame in crisis communication. AB - Incidents of intentional food contamination can produce ripple effects in consumers such as reduced trust and increased anxiety. In their postcrisis communication, food companies often direct the blame at the perpetrator in an effort to mitigate potential losses and regain consumer trust. The attempt to placate consumers may, in itself, potentially create psychological ripple effects in message readers. This study examined the interacting influence of two message characteristics: identity of the perpetrator of the crime (in-group/out-group membership), and the attribution of blame (reason why the perpetrator committed the crime), with message receiver characteristic (cultural identity) on psychological ripple effects such as blame, trust, anxiety, and future purchase intention. Results indicated that although group membership of the perpetrator was not significant in predicting outcomes for the organization, the attribution communicated in the message was. American message receivers blamed the organization more and trusted it less when personal dispositional attributions were made about the perpetrator. Asian message receivers blamed the organization more and trusted it less when situational attributions were made about the perpetrator. Lowered trust in the company and increased anxiety correlated with lower purchase intent for both American and Asian message receivers. Implications for crisis message design are discussed. PMID- 22050443 TI - A balanced translocation disrupts SYNGAP1 in a patient with intellectual disability, speech impairment, and epilepsy with myoclonic absences (EMA). AB - Epilepsy with myoclonic absences (EMA) is a rare form of generalized epilepsy occurring in childhood and is often difficult to treat. The underlying etiology of EMA is unknown in the majority of patients. Herein, we describe a patient with EMA and intellectual disability who carries a de novo balanced translocation: t(6;22)(p21.32;q11.21). We mapped the translocation breakpoints by fluorescence in situ hybridization (FISH), and the breakpoint at 6p21.32 was found to truncate the N-methyl-d-aspartate (NMDA)-receptor associated gene SYNGAP1. The breakpoint at 22q11.21 was within a highly variable region without known protein-coding genes. Mutations of SYNGAP1 are associated with nonsyndromal intellectual disability (NSID). Two-thirds of the patients described so far also have generalized epilepsy. This finding, together with our report, suggests that dysfunction of SYNGAP1 contributes to the development of generalized epilepsy, including EMA. PMID- 22050444 TI - Acceptance of a semi-custom hearing protector by manufacturing workers. PMID- 22050445 TI - Acute liver failure in young children with systemic-onset juvenile idiopathic arthritis without macrophage activation syndrome: report of two cases. AB - Acute liver failure (ALF) with macrophage activation syndrome (MAS) is well known as a complication of systemic-onset juvenile idiopathic arthritis (S-JIA). However, liver failure without overt MAS is rare in S-JIA. We encountered two Japanese children with S-JIA in whom ALF developed during the remission of clinical manifestations. ALF without MAS was improved with plasma exchange and cyclosporine A combined with pulse methylprednisolone. PMID- 22050446 TI - Relationship between dose of cloprostenol and age of corpus luteum on the luteolytic response of early dioestrous mares: a field study. AB - The objective of this study was to establish and characterize the relationship between the dose of cloprostenol (37.5, 250, 500 and 750 MUg) and the age of the early corpus luteum (CL) (80, 88, 96, 104 and 112 h) on the luteolytic response of mares. Behavioural oestrus and ultrasonographic signs of return to oestrus were considered as the occurrence of full luteolysis. A total of 298 mares were divided into groups according to dose of cloprostenol and CL age. There was an effect of dose of cloprostenol (p < 0.001) and age of the CL at the time of treatment (p < 0.001) on the percentage of mares with full luteolysis. The efficacy of 37.5 MUg of d-cloprostenol was similar to that of 250 MUg of d,l cloprostenol (p > 0.05); and that of 500 similar to that of 750 MUg (p > 0.05). The higher dose groups (500 and 750 MUg) induced full luteolysis more frequently than the lower dose groups (37.5 and 250 MUg) 96-104 h post-ovulation. There was no effect of CL age or cloprostenol dose on the interovulatory interval (p > 0.05). In conclusion, the effect of cloprostenol on the percentage of mares undergoing full luteolysis is dose-dependent. However, this effect is only evident in mares with CLs aged between 96 and 104 h. There is no advantage of administering more than 500 MUg of d,l-cloprostenol (Estrumate((r))), to obtain a higher percentage of mares with full luteolysis in mares with CLs aged 80-112 h. PMID- 22050447 TI - Length of hospital stay is shorter in black and ethnic minority patients with diabetes. PMID- 22050448 TI - Inhibition of cortactin and SIRT1 expression attenuates migration and invasion of prostate cancer DU145 cells. AB - OBJECTIVES: Cortactin is overexpressed in various types of cancer and enhances cell motility. It has been recently reported that silent mating type information regulation 2 homolog 1 interacts with cortactin and promotes cell migration. Here, we examined the role of cortactin and silent mating type information regulation 2 homolog 1 in migration and invasion of prostate cancer cells. METHODS: The cortactin expression levels in DU145, LNCaP and PC3 prostate cancer cells, and in PrEC normal human prostate epithelial cells were evaluated by western blot analysis. In DU145 cells, the expression of cortactin or silent mating type information regulation 2 homolog 1 was inhibited by small interfering RNA, and the effects of their knockdown on migration and invasion were examined by cell migration and invasion assays. To determine the localization of cortactin and silent mating type information regulation 2 homolog 1, western blot and immunofluorescence microscopic analyses were carried out. The functional interaction between silent mating type information regulation 2 homolog 1 and cortactin was also studied by in vivo acetylation assay. RESULTS: The protein expression of cortactin was significantly higher in DU145 cells than in other cell lines. Knockdown of cortactin or silent mating type information regulation 2 homolog 1 expression inhibited both migration and invasion of DU145 cells. Similarly to cortactin, silent mating type information regulation 2 homolog 1 was found to be predominantly expressed in the cytoplasm. Finally, the knockdown of silent mating type information regulation 2 homolog 1 expression increased the acetylation level of cortactin. CONCLUSIONS: Our findings suggest that inhibition of cortactin or silent mating type information regulation 2 homolog 1 expression attenuates migration and invasion of DU145 cells and this could represent a promising strategy to regulate metastasis of prostate cancer. PMID- 22050449 TI - Efficacy of adding sodium alginate to omeprazole in patients with nonerosive reflux disease: a randomized clinical trial. AB - Nonerosive reflux disease (NERD) is the most common form of gastroesophageal reflux disease. Patients with NERD have a lower response rate to proton pump inhibitors (PPIs) than patients with erosive esophagitis when gauged from relief of heartburn. Sodium alginate decreases the acidity of refluxate and protects the esophageal mucosa. However, whether the addition of sodium alginate to PPI therapy can improve NERD symptoms remains unknown. Accordingly, the aim of this study was to evaluate the efficacy of adding sodium alginate to basal PPI therapy for NERD. Patients who had experienced heartburn on at least 2 days per week during the 1-month period before entering the study and had no endoscopic mucosal breaks (grade M or N according to Hoshihara's modification of the Los Angeles classification) were randomized to one of two treatments for 4 weeks: omeprazole (20 mg once daily) plus sodium alginate (30 mL four times a day) (group A) or omeprazole (20 mg once daily) alone (group B). Eighty-seven patients were enrolled, and 76 patients were randomly assigned to group A (n = 36) or group B (n = 40). Complete resolution of heartburn for at least 7 consecutive days by the end of treatment was significantly more common in group A (56.7%) than in group B (25.7%). One patient from group A had mild drug-related diarrhea that was not clinically serious. In conclusion, omeprazole combined with sodium alginate was better than omeprazole alone in Japanese patients with NERD. PMID- 22050450 TI - Short communication: human lymphotropic virus type 1 coinfection modulates the synthesis of cytokines by peripheral blood mononuclear cells from HIV type 1 infected individuals. AB - HIV-1 and HTLV-1 infect CD4(+) T lymphocyte but little is known about the impact of coinfection on patient's immune response. In this study we have evaluated the spontaneous production of interleukin (IL)-2, IL-4, IL-6, and IL-10 and interferon (IFN)-gamma by unstimulated peripheral blood mononuclear cell (PBMC) cultures obtained from patients infected by HTLV-1, HIV-1, or both viruses. We have observed that HIV/HTLV-coinfected individuals presented significantly higher production of IL-2 and IFN-gamma compared to both HIV single-infected and HTLV single-infected individuals. IL-6 and IL-10 synthesis was similar in all infected groups, but HTLV single-infected individuals presented a lower production of IL 4. These results show that HIV/HTLV-coinfected individuals presented a profile of higher production of Th-1 cytokines, suggesting a predominant stimulus of HTLV-1 in detriment to HIV-1 infection. PMID- 22050452 TI - The in vivo expression of radiation-induced chromosomal instability has an inflammatory mechanism. AB - Ionizing radiation is unequivocally leukemogenic and carcinogenic, and this is generally attributed to DNA damage arising as a consequence of deposition of energy in the cell nucleus at the time of exposure. However, nontargeted effects, in which DNA damage is produced in nonirradiated cells as a consequence of cell signaling processes, indicate additional mechanisms. Radiation-induced chromosomal instability, a nontargeted effect with the potential to produce pathological consequences, is characterized by an increased rate of chromosome aberrations many generations after the initial insult. In this study, using a mouse model that has been well characterized with respect to its susceptibility to both radiation-induced chromosomal instability and acute myeloid leukemia, we investigated whether the underlying signaling mechanism was an inflammatory process by studying the effects of a nonsteroidal anti-inflammatory drug. Treated mice showed significant reduction in expression of the chromosomal instability phenotype 100 days postirradiation associated with reduced expression of inflammatory markers. The data support the hypothesis that the radiation-induced chromosomal instability phenotype is not an intrinsic property of the cells but a consequence of inflammatory processes having the potential to contribute secondary damage expressed as nontargeted and delayed radiation effects. PMID- 22050453 TI - FLUKA capabilities for microdosimetric analysis. AB - Delta-ray transport is important in microdosimetric studies, and how Monte Carlo models handle delta electrons using condensed histories is important for accurate simulation. The purpose of this study was to determine how well FLUKA can simulate energy deposition spectra in a tissue-equivalent proportional counter (TEPC) and produce a reliable estimate of delta-ray events produced when a TEPC is exposed to high-energy heavy ions (HZE) like those in the galactic cosmic-ray (GCR) environment. A 1.27-cm spherical TEPC with a low-pressure gas simulating a 1-MUm site, typical of the one flown on the ISS, was constructed in FLUKA, and its response was compared to experimental data for an (56)Fe-ion beam at 360 MeV/nucleon. Several narrow beams at different impact parameters were used to explain the response of the same detector exposed to a uniform field of radiation. Additionally, the effect that wall thickness had on the response of the TEPC and the range of delta rays in the tissue-equivalent (TE) wall material was investigated, and FLUKA produced the expected wall effect for primary particles passing outside the sensitive volume. A final comparison to experimental data was made for the simulated TEPCs exposed to various broad beams in the energy range of 200-1000 MeV/nucleon. FLUKA overestimated energy deposition in the gas volume in all cases. The FLUKA results differed from the experimental data by an average of 25.2% for y(F) and 12.4% for y(D). It is suggested that this difference can be reduced by adjusting the FLUKA default ionization potential and density correction factors. Accurate transport codes are desirable because of the high cost of beam time for experimental evaluation of energy deposition spectra produced by HZE ions and the flexibility that calculations offer in the TEPC engineering and design process. PMID- 22050454 TI - LEAFY controls Arabidopsis pedicel length and orientation by affecting adaxial abaxial cell fate. AB - Pedicel length and orientation (angle) contribute to the diversity of inflorescence architecture, and are important for optimal positioning of the flowers. However, relatively little is known about pedicel development. We previously described the Arabidopsis CORYMBOSA1 (CRM1)/BIG gene, which affects inflorescence architecture by controlling pedicel elongation and orientation. Here, we performed a suppressor screen using the partial loss-of-function allele crm1-13 to identify genes and pathways that affect pedicel development. We identified a hypomorph allele of the meristem identity regulator LEAFY (LFY) as the suppressor. Consistent with this, crm1 pedicels had elevated LFY levels and conditional gain of LFY function produced downward-bending pedicels. Steroid activation of 35S:LFY-GR plants caused a reduction in the cortical cell length in the abaxial domain and additional defects associated with adaxialization. Further analyses of loss of LFY function revealed that LFY is required for reduced cortical cell elongation at the adaxial side of the pedicel base. Defects in conditional LFY gain-of-function pedicels were correlated with decreased BREVIPEDICELLUS (BP) expression, while ASYMMETRIC LEAVES2 (AS2), a transcriptional repressor of BP, and REVOLUTA, a promoter of adaxial cell fate, were highly and ectopically expressed in LFY gain-of-function pedicels. LFY bound to cis-regulatory regions upstream of AS2, and as2 mutations partially suppressed the pedicel length and orientation defects caused by increased LFY activity. These data suggest that LFY activity promotes adaxial cell fate and hence the proper orientation and length of the pedicel partly by directly activating AS2 expression, which suppresses BP expression. PMID- 22050455 TI - Intelligence involves risk-awareness and intellectual disability involves risk unawareness: implications of a theory of common sense. AB - Survival in the everyday world (in both social and practical functioning) depends on one's ability to recognise and avoid going down the worst possible path, especially when doing so places one at risk of death, injury, or social disaster. Most people possess "common sense" (the ability to recognise obvious risk) but some people lack that ability and thus are at high risk of engaging in "foolish" (i.e., risk-unaware) action. People who have a cognitive impairment are much less able to recognise and avoid risk, and this is what causes them to be seen as needing protection and support. In this paper, we argue that the answer to the question "What is intellectual disability (ID)?" is more likely to come from the question "What is unintelligent behavior?" than "What is intelligence?" The answer which comes from such a question is that "ID is a common sense deficit disorder characterised by unawareness of obvious social and practical risk." Several implications of this answer are explored for the field of intellectual disability. These implications are explored primarily for adults who may have ID, given that the inspiration for this paper came from the way existing ID definitions are applied or misapplied in the US adult criminal justice system. PMID- 22050456 TI - Proteomic analysis reveals Warburg effect and anomalous metabolism of glutamine in pancreatic cancer cells. AB - In this present work, we characterized the proteomes of pancreatic ductal adenocarcinoma (PDAC) cell line PANC-1 and normal pancreatic duct cells by mass spectrometry using LTQ-Orbitrap and identified more than 1700 proteins from each sample. On the basis of the spectra count label-free quantification approach, we identified a large number of differentially expressed metabolic enzymes and proteins involved in cytoskeleton, cell adhesion, transport, transcription, translation, and cell proliferation as well. The data demonstrated that metabolic pathways were altered in PANC-1, consistent with the Warburg effect. In addition, the comparative MS analysis unveiled anomalous metabolism of glutamine, suggesting that glutamine was largely consumed as a nitrogen donor in nucleotide and amino acid biosynthesis in PANC-1. Our analysis provides a potentially comprehensive picture of metabolism in PANC-1, which may serve as the basis of new diagnostics and treatment of PDAC. PMID- 22050458 TI - Autophagy: a common road to perdition in acute brain injuries and Alzheimer's disease. PMID- 22050457 TI - Assessing quality of a worksite health promotion programme from participants' views: findings from a qualitative study in Malaysia. AB - BACKGROUND: An assessment of the process and outcomes of a health promotion programme is necessary for the continuous improvement of a programme. OBJECTIVE: To explore the participants' perceptions of the quality and effectiveness of the 'Love Your Heart Programme'. DESIGN: A qualitative study using semi-structured interviews with a purposive sample of participants of the 'Love Your Heart' programme. Interviews were based on an interview guide that grouped questions into four main subgroups: structure, process, immediate outcomes and impact. The interviews were audio-recorded, transcribed verbatim and analysed using the principles of grounded theory. RESULTS: A total of 17 interviews were conducted. The participants were satisfied with the structural aspects of the programme. Different opinions arose regarding the ideal frequency and duration of the programme. The content of the seminars was thought to be too general. There was also a lack of interest in the 'Road to a Healthy Heart' booklet. All of the respondents had positive opinions about the communication skills and attitude of the health educator. The potential advantages and disadvantages of participating in the programme were discussed. Finally, the respondents expressed their satisfaction with the programme and the impact it had on them. DISCUSSION AND CONCLUSIONS: In general, the participants who were interviewed held the programme, and the health educator conducted the programme in high regard. The suggestions that were received can be used to further improve the acceptability and feasibility of the programme. PMID- 22050459 TI - Competing statistical methods for the fitting of normal species sensitivity distributions: recommendations for practitioners. AB - A species sensitivity distribution (SSD) models data on toxicity of a specific toxicant to species in a defined assemblage. SSDs are typically assumed to be parametric, despite noteworthy criticism, with a standard proposal being the log normal distribution. Recently, and confusingly, there have emerged different statistical methods in the ecotoxicological risk assessment literature, independent of the distributional assumption, for fitting SSDs to toxicity data with the overall aim of estimating the concentration of the toxicant that is hazardous to % of the biological assemblage (usually with small). We analyze two such estimators derived from simple linear regression applied to the ordered log transformed toxicity data values and probit transformed rank-based plotting positions. These are compared to the more intuitive and statistically defensible confidence limit-based estimator. We conclude based on a large-scale simulation study that the latter estimator should be used in typical assessments where a pointwise value of the hazardous concentration is required. PMID- 22050460 TI - Clinical and neurophysiologic features of progressive myoclonus epilepsy without renal failure caused by SCARB2 mutations. AB - PURPOSE: Mutations of the SCARB2 gene cause action myoclonus renal failure syndrome (AMRF), a rare condition that combines progressive myoclonus epilepsy (PME) with severe renal dysfunction. We describe the clinical and neurophysiologic features of PME associated with SCARB2 mutations without renal impairment. METHODS: Clinical and neurophysiologic investigations, including wakefulness and sleep electroencephalography (EEG), polygraphic recording (with jerk-locked back-averaging and analysis of the EEG-EMG (electromyography) relationship by coherence spectra and phase calculation), multimodal evoked potentials, and electromyography were performed on five Italian patients with SCARB2 mutations. KEY FINDINGS: The main clinical features were adolescent-young adulthood onset, progressive action myoclonus, ataxia, absence of cognitive deterioration and, in most cases, epilepsy. The severity of the epilepsy could vary from uncontrolled seizures and status epilepticus in patients with adolescent onset to absent or rare seizures in patients with adult onset. Relevant neurophysiologic findings were a pronounced photosensitivity and massive action myoclonus associated with rhythmic myoclonic jerks at a frequency of 12-20 Hz, clinically resembling a postural tremor. The cortical origin of rhythmic myoclonus was demonstrated mainly by coherence and phase analysis of EEG-EMG signals indicating a significant EEG-EMG coupling and a direct corticospinal transfer. SIGNIFICANCE: Our patients with SCARB2 mutations showed the clinical and neurophysiologic phenotype of PME, in which epilepsy could be extremely severe, extending the spectrum reported in the typical AMRF syndrome. Patients with PME of unknown origin of adolescent or young adult onset, with these neurophysiologic features, should be tested for SCARB2 mutations, even in the absence of renal impairment. PMID- 22050461 TI - Meningococcal surface fibril (Msf) binds to activated vitronectin and inhibits the terminal complement pathway to increase serum resistance. AB - Complement evasion is an important survival strategy of Neisseria meningitidis (Nm) during colonization and infection. Previously, we have shown that Nm Opc binds to serum vitronectin to inhibit complement-mediated killing. In this study, we demonstrate meningococcal interactions with vitronectin via a novel adhesin, Msf (meningococcal surface fibril, previously NhhA or Hsf). As with Opc, Msf binds preferentially to activated vitronectin (aVn), engaging at its N-terminal region but the C-terminal heparin binding domain may also participate. However, unlike Opc, the latter binding is not heparin-mediated. By binding to aVn, Msf or Opc can impart serum resistance, which is further increased in coexpressers, a phenomenon dependent on serum aVn concentrations. The survival fitness of aVn binding derivatives was evident from mixed population studies, in which msf/opc mutants were preferentially depleted. In addition, using vitronectin peptides to block Msf-aVn interactions, aVn-induced inhibition of lytic C5b-9 formation and of serum killing could be reversed. As Msf-encoding gene is ubiquitous in the meningococcal strains examined and is expressed in vivo, serum resistance via Msf may be of significance to meningococcal pathogenesis. The data imply that vitronectin binding may be an important strategy for the in vivo survival of Nm for which the bacterium has evolved redundant mechanisms. PMID- 22050462 TI - The immune marker soluble urokinase plasminogen activator receptor is associated with new-onset diabetes in non-smoking women and men. AB - AIM: To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort. METHODS: The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort (n = 2353 generally healthy individuals). The soluble urokinase plasminogen activator receptor was measured by the ELISA method. To fulfil model assumptions, outcome analyses were stratified by age, and further by smoking, owing to the interaction between the soluble urokinase plasminogen activator receptor and smoking on new-onset diabetes (P < 0.0001). RESULTS: New onset diabetes (n = 182) was associated with increased soluble urokinase plasminogen activator receptor levels (P = 0.013). Among 699 middle-aged (41 and 51 years) and 564 older (61 and 71 years) non-smokers, participants in the upper soluble urokinase plasminogen activator receptor quartile had a sex- and age adjusted relative risk of 6.01 (95% CI 2.17-16.6, P < 0.0006) and relative risk of 3.25 (95% CI 1.51-6.98, P = 0.0025), respectively, for new-onset diabetes compared with participants in the lowest quartile. This relationship remained significant after additional adjustments for C-reactive protein and leukocytes or fasting glucose and insulin or BMI (P < 0.05). The soluble urokinase plasminogen activator receptor was not related to incident diabetes among smokers (P >= 0.85). CONCLUSIONS: In these explorative analyses, the soluble urokinase plasminogen activator receptor associated independently with incident diabetes in non-smokers, supporting an immune origin of Type 2 diabetes. Competing disease risk may explain lack of association among smokers. PMID- 22050464 TI - Fluorescence recovery after photobleaching reveals high cycling dynamics of plasma membrane aquaporins in Arabidopsis roots under salt stress. AB - The constitutive cycling of plant plasma membrane (PM) proteins is an essential component of their function and regulation under resting or stress conditions. Transgenic Arabidopsis plants that express GFP fusions with AtPIP1;2 and AtPIP2;1, two prototypic PM aquaporins, were used to develop a fluorescence recovery after photobleaching (FRAP) approach. This technique was used to discriminate between PM and endosomal pools of the aquaporin constructs, and to estimate their cycling between intracellular compartments and the cell surface. The membrane trafficking inhibitors tyrphostin A23, naphthalene-1-acetic acid and brefeldin A blocked the latter process. By contrast, a salt treatment (100 mm NaCl for 30 min) markedly enhanced the cycling of the aquaporin constructs and modified their pharmacological inhibition profile. Two distinct models for PM aquaporin cycling in resting or salt-stressed root cells are discussed. PMID- 22050465 TI - Computational methods for early predictive safety assessment from biological and chemical data. AB - INTRODUCTION: The goal of early predictive safety assessment (PSA) is to keep compounds with detectable liabilities from progressing further in the pipeline. Such compounds jeopardize the core of pharmaceutical research and development and limit the timely delivery of innovative therapeutics to the patient. Computational methods are increasingly used to help understand observed data, generate new testable hypotheses of relevance to safety pharmacology, and supplement and replace costly and time-consuming experimental procedures. AREAS COVERED: The authors survey methods operating on different scales of both physical extension and complexity. After discussing methods used to predict liabilities associated with structures of individual compounds, the article reviews the use of adverse event data and safety profiling panels. Finally, the authors examine the complexities of toxicology data from animal experiments and how these data can be mined. EXPERT OPINION: A significant obstacle for data driven safety assessment is the absence of integrated data sets due to a lack of sharing of data and of using standard ontologies for data relevant to safety assessment. Informed decisions to derive focused sets of compounds can help to avoid compound liabilities in screening campaigns, and improved hit assessment of such campaigns can benefit the early termination of undesirable compounds. PMID- 22050466 TI - Physiological changes in green stems of Vitis vinifera L. cv. Chardonnay in response to esca proper and apoplexy revealed by proteomic and transcriptomic analyses. AB - Among grapevine trunk diseases, esca proper and apoplexy commonly represent a threat for viticulture worldwide. To retrieve further information about the mechanisms activated in apoplectic and esca proper-affected plants, a two dimensional gel electrophoresis (2-DE) based analysis was conducted on green stems from 26-year-old standing vines. Symptomatic and asymptomatic stems from both apoplectic (A) and esca proper-affected (E) plants compared to control (without visual symptom since 10 years) stems were studied. Thirty-three differentially expressed proteins were identified by nanoLC-MS/MS and included into three groups conceptually defined as proteins involved in (i) metabolism and energy, (ii) stress tolerance, and (iii) defense response. For nine of them, expression of the relative mRNA's was also monitored by qRT-PCR. Proteome variations were specifically related to apoplexy and esca proper but were more similar in asymptomatic stems than in the symptomatic ones. Remarkable quantitative differences were noted for several proteins in symptomatic stems according to the expressed form, A and E. Results further indicate that similar responses are likely activated in asymptomatic stems but a various quantitative expression is triggered upon onset of apoplexy or esca proper symptoms while both kind of plants are infected by the same pathogenic fungi. PMID- 22050470 TI - World Health Organization growth charts for monitoring the growth of Australian children: time to begin the debate. AB - The recently released World Health Organization growth charts are methodologically robust, as well as clinically useful tools for monitoring the growth of children. They have been endorsed by premier organisations such as the Royal College of Paediatrics and Child Health (UK), Canadian Pediatric Society, Australian Breastfeeding Association, United Nations Standing Committee on Nutrition, International Union of Nutrition Sciences, International Pediatric Association and the European Childhood Obesity Group. The Centers for Disease Control and Prevention (CDC) as well as the American Academy of Pediatrics have also recently endorsed these charts for the 0- to 24-month age group in USA. These growth charts have been adopted by many countries including Canada, UK and New Zealand. Nearly 140 countries are at various stages of implementing them. They offer significant advantages over the currently used CDC 2000 growth charts. They have the potential to contribute in reducing the worldwide incidence of obesity as well as under nutrition in children. Except Northern Territory, Australia continues to use the CDC 2000 growth charts. Paediatricians need to initiate and lead robust debate involving key stakeholders about the implementation of World Health Organization growth charts for monitoring the growth of Australian infants and children. PMID- 22050471 TI - Ganoderma lucidum protects liver mitochondrial oxidative stress and improves the activity of electron transport chain in carbon tetrachloride intoxicated rats. AB - AIM: Liver injuries induced by carbon tetrachloride (CCl(4) ) cause mitochondrial stress and disruption of membrane potential resulting in apoptosis. In this study, we evaluated the effects of Ganoderma lucidum against CCl(4) (1:5 v/v in paraffin oil, 1.5 mL/kg, i.p) induced deterioration of the activities of mitochondrial enzymes and electron transport chain complexes in the liver mitochondria. METHODS: Ganoderma lucidum (100 and 250 mg/kg) was administered once daily for 15 days prior to the CCl(4) administration. alpha-Tocopherol (100 mg/kg, p.o.) was used as the standard. Hepatic damage was assessed by determining the activities of serum transaminases (SGPT and SGOT) and alkaline phosphatase (ALP), 24 h after CCl(4) injection. The activities of mitochondrial dehydrogenases as well as mitochondrial complexes I, II, III, and IV were evaluated. RESULTS: Activities of SGPT, SGOT and ALP were significantly (P < 0.01) elevated whereas, the activities of mitochondrial enzymes were significantly (P < 0.01) decreased by the CCl(4) challenge. The mitochondrial reactive oxygen species level was enhanced and mitochondrial membrane potential was declined significantly. Administration of G. lucidum significantly and dose independently protected liver mitochondria. CONCLUSION: The findings suggest that protective effect of G. lucidum against hepatic damage could be mediated by ameliorating the oxidative stress; restoring the mitochondrial enzyme activities and membrane potential. PMID- 22050472 TI - Seeding plaques in Alzheimer's disease. PMID- 22050473 TI - Cost-effectiveness of rosuvastatin 20 mg for the prevention of cardiovascular morbidity and mortality: a Swedish economic evaluation of the JUPITER trial. AB - OBJECTIVE: This study estimated the long-term health outcomes, healthcare costs, and cost-effectiveness of rosuvastatin 20 mg therapy in primary prevention of major cardiovascular disease (CVD) in a Swedish population. METHODS: Based on data from the JUPITER trial, long-term CVD outcomes with rosuvastatin vs no active treatment were estimated for patients with an elevated baseline CVD risk (Framingham CVD score >20%, sub-population of JUPITER population) and for a population similar to the total JUPITER population. Using a decision-analytic model, trial CVD event rates were combined with epidemiological and cost data specific for Sweden. First and subsequent CVD events and death were estimated over a lifetime perspective. The observed relative risk reduction was extrapolated beyond the trial duration. Incremental effectiveness was measured as life-years gained (LYG) and quality-adjusted life-years (QALYs) gained. RESULTS: Treating 100,000 patients with rosuvastatin 20 mg was estimated to avoid 14,692 CVD events over the lifetime (8021 non-fatal MIs, 3228 non-fatal strokes, and 4924 CVD deaths) compared to placebo. This translated into an estimated gain of 42,122 QALYs and 36,865 total life years (LYG). Rosuvastatin was both more effective and less costly over a lifetime perspective, and rosuvastatin is subsequently a dominant alternative compared to no treatment in the assessed population. Using the overall JUPITER population, rosuvastatin was dominant for the lifetime horizon. In the sensitivity analysis, rosuvastatin was the dominant treatment strategy over a 20-year time horizon, and cost-effective with an incremental cost-effectiveness ratio (cost per QALY) of SEK 1783 over a 10-year time horizon. LIMITATIONS: Some model inputs were derived from literature or other data sources, but uncertainty was controlled by sensitivity analyses. CONCLUSIONS: Results indicate that rosuvastatin 20 mg treatment is a cost effective option vs no-treatment in patients with Framingham CVD risk >20% in Sweden and might even be cost saving if taking a long-term perspective. PMID- 22050474 TI - Etiopathological aspects of achalasia: lessons learned with Hirschsprung's disease. AB - The etiology of primary esophageal achalasia is largely unknown. There is increasing evidence that genetic alterations might play an important but underestimated role. Current knowledge of the genetic base of Hirschsprung's disease in contrast is far more detailed. The two enteric neuropathies have several clinical features in common. This association may also exist on a cellular and molecular level. The aim of this review is to enlighten those etiopathogenetic concepts of Hirschsprung's disease that seem to be useful in uncovering the pathological processes causing achalasia. Three aspects are looked at: (i) the genetic base of Hirschsprung's disease, particularly its major susceptibility gene rearranged during transfection and its potential reference to achalasia; (ii) the altered motor functions in both conditions with loss of inhibitory innervation and interstitial cell pathology; and (iii) the involvement of these motility disorders in genetic syndromes. PMID- 22050475 TI - Incidence and implications of negative serum thyroglobulin but positive I-131 whole-body scans in patients with well-differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal. AB - AIMS: To evaluate the incidence and clinical implications of a positive whole body I-131 scan but negative stimulated serum Tg/TgAb level following an ablative or diagnostic I-131 dose in patients with well-differentiated thyroid cancer and whether there is a difference in incidence if prepared with thyroid hormone withdrawal compared with rhTSH stimulation. METHODS: I-131 scan findings, serum Tg/TgAb levels, TNM stage and method of thyroid tissue stimulation in 193 consecutive patients (138F, 55M) with well-differentiated thyroid cancer undergoing postoperative ablative I-131 therapy and 121 consecutive (94F, 27M) patients undergoing diagnostic I-131 surveillance scans were retrospectively reviewed. Comparisons of proportions were performed using Chi-square tests. Clinical, biochemical and I-131 scan follow-up data were obtained for each patient cohort. RESULTS: 39/193 (20.2%) postablative I-131 and 10/121 (8.3%) diagnostic I-131 patients had negative stimulated serum Tg/TgAb levels but positive I-131 scans for residual thyroid tissue. Nine (4.7%) of the postablative patients had I-131 uptake in the lateral neck suspicious for loco-regional metastatic disease. In the postablative I-131 group, 38/169 (22.5%) prepared with rhTSH compared to 1/24 (4.2%) prepared with thyroid hormone withdrawal were Tg/TgAb negative but I-131 scan positive (P = 0.04). Follow-up of 21/39 postablative I-131 patients with negative Tg/TgAb but positive I-131 scans confirmed a significant proportion of patients (4/21) (19.1%), remained Tg/TgAb negative/I-131 scan positive, some of whom had higher-risk disease at original diagnosis (2/4) (50%). CONCLUSIONS: Our study confirms that in the setting of I 131 ablation therapy or diagnostic I-131 scanning, a significant proportion of patients (20.2% and 8.3%, respectively) have residual benign or malignant thyroid tissue on whole-body scanning despite a negative stimulated serum Tg level. Whether such patients who would otherwise be missed as having residual thyroid tissue on serum Tg testing alone have a worse clinical outcome remains uncertain. Our findings do however suggest performing both stimulated serum Tg/TgAb levels and I-131 scans for the follow-up of patients with higher-risk thyroid cancer may be important. There may also be a slightly higher incidence of this phenomenon in patients prepared with rhTSH rather than by thyroxine withdrawal. PMID- 22050477 TI - Changing healthcare utilization patterns in diabetes mellitus: case-control studies 1 year and 8 years after diagnosis. AB - AIMS: To describe healthcare utilization patterns in young and middle-aged patients with diabetes 1 year and 8 years after diagnosis and to compare with the general population at two time points, 16 years apart. METHODS: Four cohorts with disease duration of 1 year or 8 years were selected from the Diabetes Incidence Study in Sweden, which registers all incident cases of diabetes in the 15- to 34 year age group. Control subjects were selected from the population register matched by age, sex and county of residence. A postal questionnaire was sent to the 1983 and 1992 cohorts in 1991 and 1993, and to the 1999 and 2008 cohorts in 2007 and 2009. Nine hundred and thirteen patients with diabetes and 1679 control subjects responded. RESULTS: One year after diagnosis, 49% of patients with diabetes in the 1992 cohort compared with 4.2% in the 2008 cohort reported visits to departments of internal medicine and endocrinology. A similar pattern was seen 8 years after diagnosis. The use of day care was 4-5 times higher among patients with diabetes compared with control subjects. Utilization of outpatient hospital care was higher among patients with diabetes compared with control subjects, even when excluding visits to diabetes clinics. CONCLUSIONS: Excess use of health care among patients with diabetes remained 16 years after the first follow-up. Utilization patterns were stable, except for a major decrease in inpatient care 1 year after diagnosis and an increase in day care 8 years after diagnosis. Observed changes probably reflect successive reforming of diabetes care in Sweden. PMID- 22050476 TI - Female reproductive factors and risk of seizure or epilepsy: data from the Nurses' Health Study II. AB - Reproductive factors are associated with seizures in women with epilepsy. We prospectively examined the association between reproductive factors and the risk of adult-onset isolated seizure, epilepsy, or any unprovoked seizure (defined as single unprovoked seizure or epilepsy) among 114,847 Nurses' Health Study II participants followed from 1989 to 2005. Validated seizure questionnaires and medical records were used to confirm incident cases of isolated seizure (n = 95) or epilepsy (n = 151). Overall, there were no significant associations between any reproductive factor and risk of any unprovoked seizure (n = 196). However, menstrual irregularity at ages 18-22 years was specifically associated with an increased risk of epilepsy [relative risk (RR) 1.67, 95% confidence interval (CI) 1.12-2.51]. Menstrual irregularity during follow-up (RR 2.21, 95% CI 1.16-4.20) and early age at menarche (<12 years vs. 12-13 years; RR 1.76, 95% CI 1.10-2.81) increased the risk of isolated seizure. Oral contraceptive use and parity were not associated with isolated seizure or epilepsy. Therefore, menstrual factors were associated with risk of seizure and epilepsy. PMID- 22050478 TI - 'Remote' adiabatic photoinduced deprotonation and aggregate formation of amphiphilic N-alkyl-N-methyl-3-(pyren-1-yl)propan-1-ammonium chloride salts. AB - The absorption and emission properties of a series of amphiphilic N-alkyl-N methyl-3-(pyren-1-yl)propan-1-ammonium chloride salts were investigated in solvents of different polarities and over a wide concentration range. For example, at 10(-5) M concentrations in tetrahydrofuran (THF), salts with at least one N-H bond exhibited broad, structureless emissions even though time-correlated single photon counting (TCSPC) experiments indicated negligible static or dynamic intermolecular interactions. Salts with a butylene spacer or lacking an N-H bond showed no discernible structureless emission; their emission spectra were dominated by the normal monomeric fluorescence of a pyrenyl group and the TCSPC histograms could be interpreted on the basis of intramolecular photophysics. The broad, structureless emission is attributed to an unprecedented, rapid, adiabatic proton-transfer to the medium, followed by the formation of an intramolecular exciplex consisting of amine and pyrenyl groups. The proposed mechanism involves excitation of a ground-state conformer of the salts in which the ammonium group sits over the pyrenyl ring due to electrostatic stabilization. At higher concentrations, with longer N-alkyl groups, or in selected solvents, electronic excitation of the salts led to dynamic and static excimeric emissions. For example, whereas the emission spectrum of 10(-3) M N-hexyl-N-methyl-3-(pyren-1 yl)propan-1-ammonium chloride in THF consisted of comparable amounts of monomeric and excimeric emission, the emission from 10(-5) M N-dodecyl-N-methyl-3-(pyren-1 yl)propan-1-ammonium chloride in 1:9 (v:v) ethanol/water solutions was dominated by excimeric emission, and discrete particles near micrometer size were discernible from confocal microscopy and dynamic light scattering experiments. Comparison of the static and dynamic emission characteristics of the particles and of the neat solid of N-dodecyl-N-methyl-3-(pyren-1-yl)propan-1-ammonium chloride indicate that molecular packing in the microparticles and in the single crystal are very similar if not the same. It is suggested that other examples of the adiabatic proton transfer found in the dilute concentration regime with the pyrenyl salts may be occurring in very different systems, such as in proteins where conformational constraints hold ammonium groups over aromatic rings of peptide units. PMID- 22050479 TI - Looking back, moving forward: towards a game-changing response to AIDS. PMID- 22050480 TI - Creating a different international HIV response for young people. AB - This paper demonstrates that certain notions of young people in the HIV and AIDS response reveal an overly generalised understanding of 'youth' that does not reflect a realistic view of young people's identity and lives. Faulty stereotypes of 'youth'--such as the perceptions that young people are necessarily victims or risk-takers--result in many HIV programmes based on generalisations about young people, rather than their actual needs and realities. These stereotypes and generalisations dominate million dollar prevention programmes that have little effect on HIV incidence rates amongst young people. To create a different future for young people and achieve real and lasting change, this paper recommends three discrete but interrelated actions for the international HIV community to undertake now; to base programmes on definitions of young people that emerge from the setting in which the programme will be implemented; to ensure HIV prevention programming is targeted at specific groups of young people, rather than a 'one size-fits-all' package; and to incorporate structural approaches into AIDS programming to address the underlying factors that make younger age groups more vulnerable to HIV--including age-related stigma, discrimination and human rights abuses. PMID- 22050481 TI - Criminalising consensual sexual behaviour in the context of HIV: consequences, evidence, and leadership. AB - This paper provides an overview of the use of the criminal law to regulate sexual behaviour in three areas of critical importance: (1) HIV exposure in otherwise consensual sex, (2) sex work and (3) sexual activity largely affecting sexual minorities. It analyses criminal law pertaining to these three distinct areas together, allowing for a more comprehensive and cohesive understanding of criminalisation and its effects. The paper highlights current evidence of how criminalisation undermines HIV prevention and treatment. It focuses on three specific negative effects of criminalisation: (1) enhancing stigma and discrimination, (2) undermining public health intervention through legal marginalisation and (3) placing people in state custody. The paper also highlights gaps in evidence and the need for strong institutional leadership from UN agencies in ending the criminalisation of consensual sexual activity. This paper serves two goals: (1) highlighting the current state of research and emphasising where key institutions have or have not provided appropriate leadership on these issues and (2) establishing a forward-looking agenda that includes a concerted response to the inappropriate use of the criminal law with respect to sexuality as part of the global response to HIV. PMID- 22050482 TI - Cytokinin-facilitated proteolysis of ARABIDOPSIS RESPONSE REGULATOR 2 attenuates signaling output in two-component circuitry. AB - Cytokinins propagate signals via multiple phosphorelays in a mechanism similar to bacterial two-component systems. In Arabidopsis, signal outputs are determined by the activation state of transcription factors termed type-B Arabidopsis response regulators (ARRs); however, their regulatory mechanisms are largely unknown. In this study, we demonstrate that the proteolysis of ARR2, a type-B ARR, modulates cytokinin signaling outputs. ARR2-hemagglutinin (HA) is rapidly degraded by cytokinin treatment, but other type-B ARRs, such as ARR1-HA, ARR10-HA, ARR12-HA and ARR18-HA, are not. ARR2 degradation is mediated by the 26S proteasome pathway, and requires cytokinin-induced phosphorylation of Asp80 residue in the receiver domain. Through mutational analysis of amino acid residues in the receiver domain, we found that substitution of Lys90 with Gly inhibits ARR2 degradation. ARR2(K90G) -HA in transgenic Arabidopsis conferred enhanced cytokinin sensitivity in various developmental processes, including primary root elongation, callus induction, leaf senescence and hypocotyl growth. ARR2(K90G) HA increased the expression of type-A ARRs, primary cytokinin-responsive genes and indicators of signaling output in two-component circuits. Expression of ARR2(K90G) -HA from the native ARR2 promoter in the arr2-4 knock-out mutant also increased cytokinin sensitivity. In conclusion, ARR2 proteolysis is involved in the maintenance of the primary signaling output for normal developmental processes mediated by cytokinin in Arabidopsis. PMID- 22050484 TI - Scientific consensus forum to review the evidence underpinning the recommendations of the Australian SIDS and Kids Safe Sleeping Health Promotion Programme--October 2010. AB - This paper summarises a 1-day scientific consensus forum that reviewed the evidence underpinning the Australian SIDS and Kids Safe Sleeping Health Promotion Programme. The focus was on each of the potentially modifiable risk factors for sudden unexpected deaths in infancy, including sudden infant death syndrome (SIDS) and fatal sleeping accidents. In particular infant sleeping position, covering of the face, exposure to cigarette smoke, room sharing, unsafe sleeping environments, bed sharing, immunisation, breastfeeding, pacifier use and Indigenous issues were discussed in depth. The participants recommended that future 'Reducing the Risk' campaign messages should focus on back to sleep, face uncovered, avoidance of cigarette smoke before and after birth, safe sleeping environment, room sharing and sleeping baby in own cot. PMID- 22050485 TI - Azithromycin in periodontal treatment: more than an antibiotic. AB - Azithromycin is a macrolide antibiotic used extensively in medicine for the treatment of a wide range of infections such as upper respiratory tract infections, middle ear infections, sexually transmitted infections and trachoma. It is also effective against the most common periodontopathogens. The versatility of the macrolides extends beyond their antibiotic properties as a result of their well-documented immune-modulating/anti-inflammatory effects. Macrolides, including azithromycin, are therefore used to treat diseases not associated with bacteria, such as severe asthma, chronic obstructive pulmonary diseases and, more recently, cystic fibrosis. Azithromycin is concentrated in neutrophils, macrophages and particularly fibroblasts; all of these cells are central players in the pathogenesis of most periodontal diseases. This paper reviews the diverse properties of azithromycin and the clinical periodontal studies of its effects in both the treatment of periodontitis and in resolving drug-related gingival overgrowth. Evidence exists to support the use of a single course of azithromycin in the treatment of advanced periodontal diseases. Azithromycin could have a triple role in the treatment and resolution of periodontal diseases: suppressing periodontopathogens, anti-inflammatory activity and healing through persistence at low levels in macrophages and fibroblasts in periodontal tissues, even after a single course of three tablets. If future periodontal research confirms these properties, it could become a valuable host-modulator in periodontal treatment. PMID- 22050483 TI - A single beta adaptin contributes to AP1 and AP2 complexes and clathrin function in Dictyostelium. AB - The assembly of clathrin-coated vesicles is important for numerous cellular processes, including nutrient uptake and membrane organization. Important contributors to clathrin assembly are four tetrameric assembly proteins, also called adaptor proteins (APs), each of which contains a beta subunit. We identified a single beta subunit, named beta1/2, that contributes to both the AP1 and AP2 complexes of Dictyostelium. Disruption of the gene encoding beta1/2 resulted in severe defects in growth, cytokinesis and development. Additionally, cells lacking beta1/2 displayed profound osmoregulatory defects including the absence of contractile vacuoles and mislocalization of contractile vacuole markers. The phenotypes of beta1/2 null cells were most similar to previously described phenotypes of clathrin and AP1 mutants, supporting a particularly important contribution of AP1 to clathrin pathways in Dictyostelium cells. The absence of beta1/2 in cells led to significant reductions in the protein amounts of the medium-sized subunits of the AP1 and AP2 complexes, establishing a role for the beta subunit in the stability of the medium subunits. Dictyostelium beta1/2 could resemble a common ancestor of the more specialized beta1 and beta2 subunits of the vertebrate AP complexes. Our results support the essential contribution of a single beta subunit to the stability and function of AP1 and AP2 in a simple eukaryote. PMID- 22050486 TI - Robotic versus open distal ureteral reconstruction and reimplantation for benign stricture disease. AB - BACKGROUND AND PURPOSE: Minimally invasive techniques are currently used for numerous urologic procedures, given decreased morbidity and equivalent outcomes to open surgery. There is, however, a relative paucity of data related to robot assisted ureteral reimplantation (RAUR) in adult patients for benign stricture disease. We sought to determine the periprocedure outcomes of open distal ureteral reimplantation vs RAUR at our institution. PATIENTS AND METHODS: We retrospectively identified 10 consecutive mid/distal RAUR procedures performed by one surgeon since 2005. Twenty-four patients undergoing open mid/distal ureter reconstruction over the same period were identified, and 10 controls matched for age and body mass index (BMI) were used for comparison. Demographic, operative, and clinical/radiographic outcomes were compared. RESULTS: Etiology of the strictures included stone disease (n=8, 40%), iatrogenic injury during previous abdominopelvic surgery (n=10, 50%), or other causes (n=2, 10%). None of the robotic procedures necessitated conversion to open surgery. No intraoperative complications occurred. Six neocystostomies, three psoas hitches, and one Boari flap were completed in an open fashion. Four neocystostomies, four psoas hitches, and two Boari flaps were performed in the RAUR group. Estimated blood loss (30.6 vs 327.5 mL, P=0.001) and length of hospital stay (2.4 vs 5.1 d, P=0.01) were significantly reduced in the robotic group. Median BMI (29.4+/-5.3 vs 26.5+/-5.2, P=0.130) and operative time in minutes (306.6 vs 270.0 min, P=0.316) were higher in the robotic group, although these were not statistically significant. None of the patients in either group had clinical or radiologic evidence of recurrent stricture disease at a median follow-up of 30 and 24 months in the open and RAUR groups, respectively. The retrospective comparative nature of this study may introduce selection bias. CONCLUSIONS: In experienced hands, RAUR for mid/distal benign ureteral strictures appears to be a reasonable alternative to open surgery. PMID- 22050487 TI - Which is more important in predicting the outcome of extracorporeal shockwave lithotripsy of solitary renal stones: stone location or stone burden? AB - PURPOSE: To assess the effect of stone location and burden on the outcome of extracorporeal shockwave lithotripsy (SWL) as a primary treatment of solitary renal stone. PATIENTS AND METHODS: The study included 438 patients with a solitary renal stone who underwent SWL as a primary treatment for their stones. All were evaluated by plain radiography of the kidneys, ureters, and bladder (KUB), ultrasonography, intravenous urography, or noncontrast enhanced CT before SWL and followed up for 3 months after treatment by KUB radiography and/or ultrasonography. Patients were classified into four groups according to stone location (renal pelvis, lower, middle, and upper calix) and three groups according to stone burden (<= 1 cm(2), 1.1-2 cm(2), and >2 cm(2)). Treatment outcome was considered successful if no residual fragments (stone free) or clinically insignificant nonobstructing residuals less than 4 mm remained after 3 months of follow-up. RESULTS: The mean age of the patients was 45.1 +/- 12.5 years. The mean stone burden, number of sessions, and shockwaves for the whole study were 1.3 +/- 0.49 cm(2), 2.1 +/- 0.7 sessions, and 5616.6 +/- 2017.4 shockwaves, respectively. The stone-free rate of the study was 65.1%. The stone free rates of the stones in the renal pelvis, lower, middle, and upper calices were 72.4%, 56%, 55.6%, and 69%, respectively. The stone-free rate of the stones <= 1 cm(2), 1.1 to 2 cm(2), and >2 cm(2) was 50.2%, 39.6%, and 10.2%, respectively (P<0.05). CONCLUSION: Stone burden rather than stone location is considered as a predicting factor for the outcome of SWL in a solitary renal stone, especially in the renal pelvis and lower calix. PMID- 22050488 TI - Multi-institutional analysis of robot-assisted partial nephrectomy for renal tumors >4 cm versus <= 4 cm in 445 consecutive patients. AB - BACKGROUND AND PURPOSE: Robot-assisted partial nephrectomy (RPN) has emerged as a viable approach to minimally invasive surgery for small renal tumors. There are few reports of RPN for tumors >4 cm. Our objective was to evaluate outcomes of RPN for tumors >4 cm compared with RPN for tumors <= 4 cm in a large multi institutional study. PATIENTS AND METHODS: We reviewed data for 445 consecutive patients who underwent RPN by experienced surgeons at four academic institutions from 2006 to 2010. Patients were stratified into two groups according to radiographic tumor size. Patient demographics, perioperative outcomes, and oncologic outcomes were recorded. RESULTS: A total of 83 of 445 (18.7%) patients had tumors >4 cm with a median radiographic tumor size of 5.0 cm (4.1-11 cm). Patients with tumors >4 cm had a higher proportion of hilar tumors (9.8% vs 4.7%, P<0.001), a higher mean R.E.N.A.L. nephrometry score (8.0 vs 6.3, P<0.01), longer warm ischemia time (WIT) (24 vs 17 min, P<0.001), and an increased rate of collecting system repair (72.2% vs 51.6%, P=0.006) compared with patients with tumors <= 4 cm. Functional outcomes and complications were similar between groups. There were no positive margins in patients with tumors >4 cm and only one recurrence. CONCLUSIONS: In the largest multi-institutional series of RPN for tumors >4 cm, we demonstrate safety, feasibility, and efficacy of RPN for tumors >4 cm. Patients with tumors >4 cm had a higher nephrometry score, longer WIT, and slightly higher estimated blood loss compared with patients who had tumors <= 4 cm, but there was no increased risk of adverse outcomes in the hands of experienced surgeons. PMID- 22050489 TI - Introduction and validation of the American Urological Association Basic Laparoscopic Urologic Surgery skills curriculum. AB - BACKGROUND AND PURPOSE: The Fundamentals of Laparoscopic Surgery (FLS(TM)) skills curriculum has validity evidence supporting use for assessing laparoscopic skills for general surgeons. As charged by the American Urological Association (AUA) Laparoscopy, Robotic, and New Surgical Technology Committee, we sought to develop and validate a urology-specific FLS, referred to as the Basic Laparoscopic Urologic Surgery (BLUS((c))) skills curriculum. The psychomotor component consists of three existing FLS tasks and one new clip-applying task. MATERIALS AND METHODS: An animate renal artery model was designed for a clip-applying skills task. We assessed the acceptability and construct validity of using BLUS for basic laparoscopic skills assessment for urologists. A cohort of practicing urologists, fellows, residents, and medical students completed the tasks at the AUA Annual Meetings in 2010 and 2011. RESULTS: All exercises were acceptable and demonstrated excellent face and content validity (>4.5/5 on a five-point Likert scale). Practicing clinical urologists (N=81) outperformed residents and medical students (N=35) in time to completion of circle cut (P<0.01) and in keeping scissor tips toward the center of the circle (P<0.01). Practicing urologists who reported >3 laparoscopic procedures per week were faster at the peg-transfer exercise (P<0.05) and the cutting exercise (P<0.01) than those reporting one to two procedures. More errors were committed for clip-applying among practicing urologists who perform one to two laparoscopic procedures (1.24) vs. those who perform >3 procedures (0.57) per week (P<0.01). CONCLUSIONS: All exercises including the novel clip-applying model demonstrated good acceptability and evidence of construct validity (face, content, concurrent and convergent validity) for assessment of basic laparoscopic skill for urologic surgeons. PMID- 22050490 TI - Pelvic lymph node dissection for patients with elevated risk of lymph node invasion during radical prostatectomy: comparison of open, laparoscopic and robot assisted procedures. AB - BACKGROUND AND PURPOSE: Published outcomes of pelvic lymph node dissection (PLND) during robot-assisted laparoscopic prostatectomy (RALP) demonstrate significant variability. The purpose of the study was to compare PLND outcomes in patients at risk for lymph node involvement (LNI) who were undergoing radical prostatectomy (RP) by different surgeons and surgical approaches. PATIENTS AND METHODS: Institutional policy initiated on January 1, 2010, mandated that all patients undergoing RP receive a standardized PLND with inclusion of the hypogastric region when predicted risk of LNI was >= 2%. We analyzed the outcomes of consecutive patients meeting these criteria from January 1 to September 1, 2010 by surgeons and surgical approach. All patients underwent RP; surgical approach (open radical retropubic [ORP], laparoscopic [LRP], RALP) was selected by the consulting surgeon. Differences in lymph node yield (LNY) between surgeons and surgical approaches were compared using multivariable linear regression with adjustment for clinical stage, biopsy Gleason grade, prostate-specific antigen (PSA) level, and age. RESULTS: Of 330 patients (126 ORP, 78 LRP, 126 RALP), 323 (98%) underwent PLND. There were no significant differences in characteristics between approaches, but the nomogram probability of LNI was slightly greater for ORP than RALP (P=0.04). LNY was high (18 nodes) by all approaches; more nodes were removed by ORP and LRP (median 20, 19, respectively) than RALP (16) after adjusting for stage, grade, PSA level, and age (P=0.015). Rates of LNI were high (14%) with no difference between approaches when adjusted for nomogram probability of LNI (P=0.15). Variation in median LNY among individual surgeons was considerable for all three approaches (11-28) (P=0.005) and was much greater than the variability by approach. CONCLUSIONS: PLND, including hypogastric nodal packet, can be performed by any surgical approach, with slightly different yields but similar pathologic outcomes. Individual surgeon commitment to PLND may be more important than approach. PMID- 22050491 TI - Editorial comment for Ma et al. PMID- 22050492 TI - Severe primary obstructive megaureter in the first year of life: preliminary experience with endoscopic balloon dilation. AB - BACKGROUND AND PURPOSE: Although conservative management is indicated in most cases of primary obstructed megaureter (POM), surgery is still indicated when POM is associated with increasing dilation, symptoms, or progressive renal damage. Surgery is associated with a significant rate of complications, however, especially in the case of very large ureter in the first year of life. A valid alternative could be endoscopic high pressure balloon dilation (EHPBD) of the vesicoureteral junction (VUJ). We report the first experience with EHPBD in patients under 1 year of age who were affected by severe POM. PATIENTS AND METHODS: Five patients, aged between 6 and 12 months, were treated with EHPBD. In all patients, preoperative renal ultrasonography showed a distal ureteral dilation >=15 mm that increased at later evaluations; an obstructive pattern was detected by preoperative diuretic renography. An 8-9,8 F cystoscope, and a 3F balloon catheter (balloon maximum diameter 4 mm) was used. The VUJ was dilated for 5 minutes at 12 to 14 atm. A 4.7F Double-J stent was then positioned and left in place for 6 to 8 weeks. Ultrasonography was performed every 3 months, and renography and voiding cystourethrography the fourth month after the EHPBD. RESULTS: No operative complications were observed. All the patients showed an improvement at the ultrasonography postoperative follow-up, and there was no evidence of obstruction/reflux at the postoperative check up. CONCLUSIONS: Our preliminary results seem to indicate that EHPBD is a feasible, safe, and successful procedure. It could play a role as a minimally invasive alternative to open surgery in cases of POM that necessitate intervention in the first year of life. Longer follow-up is necessary to verify the stability of these results. PMID- 22050493 TI - Does size really matter? The impact of prostate volume on the efficacy and safety of GreenLight HPSTM laser photoselective vaporization of the prostate. AB - PURPOSE: To evaluate the efficacy and safety of GreenLight HPSTM laser photoselective vaporization of the prostate (PVP) for the treatment of benign prostatic hyperplasia (BPH) in patients with different prostate volumes. PATIENTS AND METHODS: Between July 2006 and February 2011, 207 consecutive patients were identified from a prospectively maintained urologic database. Based on preoperative prostate volume measured by transrectal ultrasonography, patients were stratified into two groups: >= 80 cc (group 1, n=57) and < 80 cc (group 2, n=150). Transurethral PVP was performed using a 120W GreenLight HPS side-firing laser system. American Urological Association Symptom Score (AUASS), quality-of life (QoL) score, maximum flow rate (Qmax), and postvoid residual (PVR) volume were measured preoperatively and at 1 and 4 weeks and 3, 6, 12, 18, 24, and 36 months postoperatively. RESULTS: Among the preoperative parameters evaluated, there were significant differences (P<0.05) in the incidence of preoperative urinary retention (1: 24.6%; 2: 7.3%), serum prostate-specific antigen level (1: 4.5 +/- 2.7; 2: 1.8 +/- 1.9 ng/mL), QoL (1: 4.2 +/- 1.1; 2: 4.7 +/- 0.9), and mean prostate volume (1: 118.1 +/- 37.9; 2: 48.5 +/- 15.5 cc), while AUASS, Qmax, and PVR were similar (P>0.05) between groups. Significant differences (P<0.05) in laser use (1: 22.8 +/- 13.3; 2: 10.4 +/- 6.4 minutes) and energy usage (1: 152.7 +/- 90.6; 2: 70.9 +/- 44.8 kJ) were also noted. Clinical outcomes (AUASS, QoL, Qmax, and PVR) showed immediate and stable improvement from baseline (P<0.05) within each group, but no significant differences between the two groups were observed during the follow-up period (P>0.05). The incidence of adverse events was low and similar in both cohorts. CONCLUSIONS: These results suggest that prostate volume has little effect on the efficacy and safety of GreenLight HPS laser PVP, and that this technique remains a viable surgical option for BPH, irrespective of preoperative prostate volume. PMID- 22050494 TI - Renal transplant lithiasis: analysis of our series and review of the literature. AB - BACKGROUND AND PURPOSE: Renal transplant lithiasis represents a rather uncommon complication. Even rare, it can result in significant morbidity and a devastating loss of renal function if obstruction occurs. We present our experience with graft lithiasis in our series of renal transplantations and review the literature regarding the epidemiology, pathophysiology, and current therapeutic strategies in the management of renal transplant lithiasis. PATIENTS AND METHODS: In a retrospective analysis of a consecutive series of 1525 renal transplantations that were performed between January 1983 and March 2007, 7 patients were found to have allograft lithiasis. In five cases, the calculi were localized in the renal unit, and in two cases, in the ureter. A review in the English language was also performed of the Medline and PubMed databases using the keywords renal transplant lithiasis, donor-gifted lithiasis, and urological complications after kidney transplantation. Several retrospective studies regarding the incidence, etiology, as well as predisposing factors for graft lithiasis were reviewed. Data regarding the current therapeutic strategies for graft lithiasis were also evaluated, and outcomes were compared with the results of our series. RESULTS: Most studies report a renal transplant lithiasis incidence of 0.4% to 1%. In our series, incidence of graft lithiasis was 0.46% (n=7). Of the seven patients, three were treated via percutaneous nephrolithotripsy (PCNL); in three patients, shockwave lithotripsy (SWL) was performed; and in a single case, spontaneous passage of a urinary calculus was observed. All patients are currently stone free but still remain under close urologic surveillance. CONCLUSION: Renal transplant lithiasis requires vigilance, a high index of suspicion, prompt recognition, and management. Treatment protocols should mimic those for solitary kidneys. Minimally invasive techniques are available to remove graft calculi. Long-term follow-up is essential to determine the outcome, as well as to prevent recurrence. PMID- 22050495 TI - Staghorn morphometry: a new tool for clinical classification and prediction model for percutaneous nephrolithotomy monotherapy. AB - BACKGROUND AND PURPOSE: Staghorn stone volume and its distribution within the collecting system, "staghorn morphometry," predicts the requirement of tract and stage for percutaneous nephrolithotomy (PCNL) monotherapy. The purpose of the study was to develop a CT urography staghorn morphometry-based prediction algorithm to predict tract(s) and stage(s) for PCNL monotherapy and classify staghorn accordingly. MATERIAL AND METHODS: A retrospective case-control design of 94 units was used. CT software calculated the total stone volume (TSV) with absolute volume and percentile volume in the pelvis, planned entry calix, favorable and unfavorable calix. Entry calix was the optimum calix chosen, keeping the relations of the ribs and adjoining viscera that could clear maximum stone volume. Unfavorable calix was defined as having an acute angle from the entry calix and infundibular width of <= 8 mm. A prediction model with odds ratio (OR) (95% confidence interval) was constructed on univariate and multivariate regression factors. RESULTS: On univariate analysis, TSV (P=0.013), unfavorable calix stone volume (0.007), and percentile distribution of stone in pelvis (0.026), pelvis and entry calix (<0.001), and unfavorable calix (0.001) predicted tracts while total stone (<0.001), pelvic stone (0.0046), and unfavorable calix stone (<0.001) volume and percentile volume in pelvis (0.04), pelvis and entry calix (0.005) and unfavorable calix (P<0.001) predicted stage. Multivariate analysis showed that unfavorable calix stone percentile volume predicted tract (area under the curve [AUC] - 0.91) while TSV and unfavorable calix stone percentile volume (AUC - 0.846) predicted stage. The OR-based prediction model suggested a need for single tract and stage PCNL vs multiple tract and stage PCNL for TSV and unfavorable calix percentile stone volume of (<5,000 mm(3) and 5%) and (>20,000 mm(3) and 10%), respectively. CONCLUSION: The model predicts the tract and stage for PCNL monotherapy. Staghorn morphometry differentiates staghorn into type 1 (single tract and stage); type 2 (single tract single/multiple stage, or multiple tract-single stage), and type 3 (multiple tract and stage). PMID- 22050496 TI - Comparison of three different analgesic protocols during shockwave lithotripsy. AB - BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) is one of the most important treatment modalities for urinary stone disease. The procedure may cause pain, and patient relaxation and cooperation are crucial in maintaining stone localization for optimal fragmentation and patient comfort during the procedure. As yet, there is not a standard analgesic protocol for patients undergoing SWL. We aimed to use three different analgesic agents and compare their efficacy during SWL in this study. PATIENTS AND METHODS: Written informed consents were obtained from 95 patients with kidney stones, and they were randomized to receive lornoxicam (group L, n=32 patients), paracetamol (group P, n=31 patients), and tramadol with a patient-controlled analgesia device (group T, n=32 patients). All groups received patient-controlled analgesia with tramadol during the SWL procedure. The intensity of pain was evaluated with a visual analog scale (VAS). RESULTS: The mean age of the patients was 41.87 +/- 16.53 years, 44.07 +/- 11.48 years, and 41.24 +/- 14.82 years in group L, group P, and group T, respectively. No significant differences were found between the three groups concerning patient age, stone location, or session duration (P>0.05). The mean VAS scores and analgesic consumption were lower in group L compared with other groups (P<0.05). CONCLUSION: The results of this study showed that additional administration of analgesics was decreased with intravenous lornoxicam in comparison with paracetamol and only tramadol. PMID- 22050497 TI - Radiopaque laser fiber for holmium: yttrium-aluminum-garnet laser lithotripsy: critical evaluation. AB - BACKGROUND AND PURPOSE: Laser energy has gained widespread use, not only in stone treatment, but also in multiple endourologic procedures such as endopyelotomy and incision of ureteral strictures. Furthermore, laser use gains access to open, laparoscopic, and robot-assisted surgery. Therefore, potential complications, such as fiber breakage and detection of these radiolucent fiber remainders, may become of interest. The aim of this study was to evaluate a prototype of a radiopaque laser fiber that was designed for lithotripsy with a holmium:yttrium aluminum-garnet laser. MATERIALS AND METHODS: A gold-clad 200-MUm optical laser fiber was evaluated for its influence on deflection, fiber degradation, as well as radiopaque property in vitro and in vivo. The results were compared with a commercially available 200 MUm optical core lithotripsy fiber. RESULTS: The gold clad prototype fiber showed radiopaque property in vitro as well as in vivo, although high body mass index reduces visibility. Introducing the fiber into a flexible ureteroscope had no influence on deflection properties or the diameter of the fully deflected tip. Fiber burn was considerably low and comparable to that of the standard fiber. CONCLUSION: The 200 MUm optical core gold-cladd fiber prototype offers comparable performance to a commercially available fiber of the same optical core diameter. Radiopaque property was proven in vitro as well as intracorporeally, thereby adding an additional safety feature to laser treatment in endourology as well as in laparoscopic and robotic surgery. PMID- 22050498 TI - Laparoendoscopic single-site radical cystectomy and urinary diversion: initial experience in China using a homemade single-port device. AB - PURPOSE: We report our initial experience with the first series of laparoendoscopic single-site (LESS) radical cystectomy and urinary diversion performed by a single surgeon using a homemade single-port device at a single institution in China. PATIENTS AND METHODS: Between December 2010 and February 2011, we performed five LESS radical cystectomis using a homemade single-port device composed of an inverted cone device of polycarbonate and a powder-free surgical glove. The port was placed into a 5-cm periumbilical incision. The conventional laparoscope and laparoscopic instruments were inserted through the single-port. No additional ports were needed for radical cystoprostatectomy and bilateral standard pelvic lymphadenectomy. Cutaneous ureterostomy and ileal conduit urinary diversion were used for our patients, respectively. Perioperatively, oncologic data and complications were collected and analyzed. RESULTS: All the procedures were completed successfully. The mean extirpative operative time was 208.2 (168-280) minutes, estimated blood loss was 270 (100 500) mL, bowel recovering time was 9.75 (6-12) days, and postoperative hospital stay was 19.5 (14-28) days. One patient needed a transfusion of 400 mL of red blood cells. The pathologic evaluation revealed negative margins and negative lymph node involvement. After the operations, one patient had a bowel obstruction, while another patient died from cardiac disease. Mean follow-up time was 143 (110-173) days. CONCLUSIONS: In our experience, LESS radical cystectomy is clinically feasible and safe for selected patients, but requires a learning curve. Our homemade single-port device is a cost-effective and convenient device. Although the initial outcomes have been promising, the long-term oncologic evaluation of these patients awaits. PMID- 22050499 TI - Photoselective GreenLightTM laser vaporization versus transurethral resection of the prostate in Greece: a comparative cost analysis. AB - PURPOSE: To compare photoselective vaporization of the prostate (PVP) using the 120W GreenLightTM laser with transurethral resection of the prostate (TURP) in terms of their cost to the Greek National Health Service (NHS) or to the Public Insurance Sickness Funds (PISF). PATIENTS AND METHODS: A prospective cost evaluation with 1-year follow-up of 60 patients with infravesical obstruction of benign prostatic hyperplasia origin who underwent o either TURP (n=30) or PVP (n=30). The cost of equipment, consumables, anesthesia, drugs, inpatient hospitalization, and complication management within 1 year postoperatively were used to calculate the cost for the NHS. PISF reimbursements to hospitals and PISF opportunity cost from the lost days of work were used to calculate PISF perspective. RESULTS: From the NHS perspective, the average cost was ?1722 ($2371) for PVP and ?2132 ($2935) for TURP. From the PISF perspective, the average cost for hospital reimbursement was ?1348 ($1856) in the case of PVP and ?938 ($1291) in the case of TURP. Nevertheless, in the case of patients still working, total PISF reimbursement cost was ?2038 ($2806) for PVP and ?2666 ($3671) for TURP. CONCLUSIONS: PVP for 40 to 70 cc prostates is preferable from the perspective of the NHS. From the perspective of PISF, PVP is less costly only in the case of patients who are still working, because patients who undergo PVP stay much less out of work. Further investigation in larger populations as well as in different protocols of PVP hospitalization and return to work times is deemed necessary to reinforce the conclusions of this study. PMID- 22050500 TI - The safety and efficacy of percutaneous nephrolithotomy for management of large renal stones in single- versus double-functioning kidney patients. AB - PURPOSE: To demonstrate the safety and efficacy of percutaneous nephrolithotomy (PCNL) for management of large renal stones between single-functioning kidney and double-kidney patients. PATIENTS AND METHODS: Thirty single-functioning kidneys and 30 double-kidney patients with a mean age of 38.5 (+/-15.6) years in the single group and 42.1 (+/-14.3) years in the double group (range 11-72 years) underwent PCNL for renal stones larger than 2 cm. The effect of PCNL on global and regional cortical activity was measured using quantitative single-photon emission CT measurement of technetium-99m ((99m)Tc) dimercaptosuccinic acid (DMSA) scan uptake by the kidneys before and 6 months after PCNL. Variables assessed were stone bulk, size, location, the number of punctures, and anatomic factors. Average hemoglobin and serum creatinine changes, mean operative time, transfusion rate, hospital stay, and different complications were also assessed. RESULTS: Mean stone size, mean hospital stay, success rate, and complications were statistically similar in both groups. Mean serum creatinine changes (preoperative and postoperative) were not statistically significant between the two groups (P=0.12). Mean hemoglobin drop (preoperative and postoperative) in both groups was significant, and there was a valuable difference between them (P=0.01). There was a significant difference in the uptake by the treated kidneys before vs after PCNL between both groups statistically (P=0.019), so that the DMSA renal uptake was obviously higher 6 months after PCNL in the double-kidney group compared with its uptake in the single-functioning kidney group. CONCLUSION: (99m)Tc-DMSA renal scan confirms that renal function was preserved or even often improved after percutaneous stone removal, and the procedure had no detrimental effects on renal function in both groups. There was no statistically significant difference between these groups in terms of morbidity and stone clearance. PMID- 22050501 TI - Outpatient simultaneous treatment of benign prostatic hyperplasia and bladder lithiasis with GreenLightTM and holmium laser. AB - PURPOSE: To evaluate our experience in the combined treatment of benign prostatic hyperplasia (BPH) and bladder lithiasis with GreenLight(TM) and holmium laser, respectively, on an outpatient basis. PATIENTS AND METHODS: From August 2006 to May 2009, 20 patients with prostatic hyperplasia and bladder lithiasis were treated. First, the lithiasis was treated, and then the GreenLight laser vaporization of the prostate was performed, both at the same surgical time and under general anesthesia. Discharge of patients was scheduled 3 to 4 hours after completion of the procedure. RESULTS: The procedure was simultaneously completed in 19 of 20 patients. The mean stone size was 2.3 (1-4) cm, and the mean prostate volume was 56.5 (30-108) cc. The mean operating time was 115 (50-190) minutes. There was a significant percentage change in maximum flow, postmicturition residual volume, and International Prostate Symptom Score, which were 129.5%, 88.4%, and 68.3%, respectively. All patients were stone free after the procedure. CONCLUSIONS: The combined transurethral treatment of BPH associated with bladder lithiasis by means of GreenLight laser vaporization and holmium laser lithotripsy on an outpatient basis can be performed safely and yields excellent results. PMID- 22050502 TI - Ex-vivo ureteroscopy at the time of live donor nephrectomy: a word of caution. PMID- 22050503 TI - Isoprostane: quantitation of renal ischemia and reperfusion injury after renal artery clamping in an animal model. AB - BACKGROUND AND PURPOSE: Laparoscopic and robotic partial nephrectomy involves temporary clamping of the renal artery, making the kidney susceptible to ischemic damage. Isoprostane represents one potential marker of oxidative injury. The objective was to determine if renal interstitial isoprostane levels can quantitate renal damage secondary to warm ischemia. A second goal is to investigate allopurinol for renoprotective abilities using this model. We chose to investigate potential renoprotection of allopurinol because previous studies have demonstrated transplant kidneys pretreated with allopurinol to have less damage from ischemia. MATERIALS AND METHODS: A microdialysis probe was inserted into the renal parenchyma of rats to allow continuous dialysis and collection of the effluent for isoprostane levels. After clamping of the renal vessels for predefined intervals of ischemia, the interstitial effluent from the probe was collected and subsequently analyzed for isoprostane levels with and without allopurinol pretreatment. RESULTS: Clamping of the renal artery and vein produced increases in isoprostane levels during the ischemic period and larger increases during reperfusion. There was a trend for increased postclamp isoprostane levels as clamp times increased. When comparing isoprostane levels in rats that did not receive allopurinol, there were significant differences between the clamp and postclamp levels of isoprostane, with allopurinol offering protection to the kidney from ischemic changes caused by clamping the renal hilum. CONCLUSIONS: Our data have demonstrated that isoprostane levels are a potential real-time marker of renal ischemia and reperfusion injury. We also found allopurinol administration demonstrated a trend toward renoprotective abilities in the hilar occluded kidney. PMID- 22050504 TI - Pediatric laparoscopic and robot-assisted laparoscopic surgery: technical considerations. AB - Laparoscopy has become an effective modality for the treatment of many pediatric urologic conditions that need both extirpative and reconstructive techniques. Laparoscopic procedures for urologic diseases in children, such as pyeloplasty, orchiopexy, nephrectomy, and bladder augmentation, have proven to be safe and effective with outcomes comparable to those of open techniques. Given the steep learning curve and technical difficulty of laparoscopic surgery, robot-assisted laparoscopic surgery (RAS) is increasingly being adopted in pediatric patients worldwide. Anything that can be performed laparoscopically in adults can be extended into pediatric practice with minor technical refinements. We review the role of laparoscopic and RAS in pediatric urology and provide technical considerations necessary to perform minimally invasive surgery successfully. PMID- 22050505 TI - Intermediate-term outcomes after renal cryoablation: results of a multi institutional study. AB - PURPOSE: To present intermediate-term oncologic efficacy of cryoablation (CA) for the treatment of patients with small renal masses in a multi-institution multisurgeon cohort. PATIENTS AND METHODS: We retrospectively reviewed billing records and tumor registries, identifying 116 renal tumors in 116 patients treated with CA by six surgeons at four institutions. Patient age, sex, tumor size, RENAL nephrometry score, complications, and recurrences were recorded. RESULTS: One hundred-sixteen patients (66.4% male, 33.6% female) with 116 tumors underwent renal mass CA with a mean follow-up of 27.4 months (range 1-112 mos). Mean tumor size was 2.76 +/- 0.97 cm (range 1.1-5.5 cm). Twenty-seven complications occurred in 23 patients for an overall complication rate of 19.8%. Low-grade complications (Clavien I and II) accounted for 92.6% (n=25) of overall complications. Seven (6%) patients had enhancement on initial imaging and were considered incomplete ablations. Local recurrence and metastatic disease developed in four and one patients, respectively. In patients with biopsy-proven renal-cell carcinoma (RCC), the 2- and 5-year recurrence-free survival (RFS) probability was 0.83 (95% confidence interval [CI]: 0.74, 0.95) and 0.77 (95% CI: 0.60, 0.94), respectively. After excluding biopsy proven RCC patients with incomplete ablations, the 2- and 5-year RFS increased to 0.91 (95% CI: 0.82, 1.00) and 0.85 (95% CI: 0.71, 1.00) respectively. CONCLUSION: CA of renal masses results in acceptable oncologic efficacy accompanied by a tolerable complication profile in a cohort with a mean follow-up of 27.4 months. CA remains a viable treatment option for small renal masses in selected patients. PMID- 22050506 TI - Laparoendoscopic single-site nephrectomy in obese living renal donors. AB - BACKGROUND AND PURPOSE: Laparoendoscopic single-site (LESS) surgery has been shown to be feasible in living donor nephrectomies (DNs). Obesity is an established risk factor for perioperative morbidity. We sought to determine whether LESS-DN is safe and effective in the obese (body mass index [BMI] >=30 kg/m(2)) population. PATIENTS AND METHODS: Between August 2009 and September 2010, 125 consecutive LESS-DN were performed; 32 patients were obese. This group was matched to 32 nonobese LESS-DN (BMI <30 kg/m(2)) patients, 32 obese conventional laparoscopic DN (obese LAP-DN) patients, and 32 nonobese LAP-DN patients. Comparison parameters included organ recovery time, operative time, estimated blood loss (EBL), warm ischemia time (WIT), incision length, complications, and recipient allograft function. RESULTS: Demographic data were similar between the groups, except BMI (P>0.0001). Organ recovery time, EBL, WIT, complications, and recipient allograft function were similar between the obese LESS-DN group and the other three groups (P>0.05). Total operative time was longer in the obese LESS-DN compared with the nonobese LAP-DN (P<0.0001); however, incision length was shorter in the obese LESS-DN group compared with either LAP group (P<0.0001). Complete LESS-DN was successful in 62 (97%) cases (two obese donor cases were converted to hand-assisted laparoscopy). CONCLUSIONS: Our results indicate that LESS-DN can be performed safely in obese donors without increased donor morbidity and similar recipient allograft outcomes compared with ideal-sized donors as well as with conventional LAP-DN patients. PMID- 22050507 TI - Preclinical evaluation of new indomethacin-eluting biodegradable urethral stent. AB - PURPOSE: To evaluate the effect of an indomethacin-eluting biodegradable urethral stent on the production of inflammatory cytokines in vitro and the degradation and biocompatibility of the new stent in vivo. MATERIALS AND METHODS: The effects of an indomethacin and indomethacin-eluting biodegradable stent on monocyte chemoattractant protein (MCP)-1, RANTES (regulated on activation, normal T-cell expressed and secreted), and transforming growth factor-beta were measured in THP 1 cells by enzyme-linked immunosorbent assay. Stents (copolymer of L-lactide and glycolide acid) that were coated with 50L/50D polylactic acid and two different concentrations of indomethacin were inserted into the rabbit urethra. Stents without the drug were used as controls. Scanning electron microscopy (SEM) was used to assess the degradation of the stents. Biocompatibility was evaluated using histologic analyses of the urethral specimen. The measurements were performed at 3 weeks and 3 months. RESULTS: Indomethacin and indomethacin releasing stent material inhibited MCP-1 and RANTES production in activated THP-1 macrophages. SEM analysis revealed that indomethacin coating had no effect on the degradation process of the stents and less epithelial polyposis had developed in the indomethacin stent group. In histologic analyses at 3 weeks, indomethacin eluting stents caused more calcification but no significant differences in other tissue reactions. At 3 months, the indomethacin-eluting stents caused less inflammatory reaction and calcification compared with the control stents. CONCLUSION: Indomethacin-eluting property can be safely added to biodegradable stents without major influence on the degradation time. The development of epithelial polyposis in the urethra can be potentially reduced by the new indomethacin-eluting urethral stents. PMID- 22050508 TI - Does the presence of median lobe affect outcomes of robot-assisted laparoscopic radical prostatectomy? AB - PURPOSE: To determine whether the presence of median lobe (ML) affects perioperative outcomes, positive surgical margin (PSM) rates, and recovery of urinary continence after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: We analyzed 1693 consecutive patients undergoing RARP performed by a single surgeon. Patients were analyzed in two groups based on the presence or not of a ML identified during RARP. Perioperative outcomes, PSM rates, and recovery of urinary continence were compared between the groups. Continence was assessed using validated questionnaires, and it was defined as the use of "no pads" postoperatively. RESULTS: A ML was identified in 323 (19%) patients. Both groups had similar estimated blood loss, length of hospital stay, pathologic stage, complication rates, anastomotic leakage rates, overall PSM rates, and PSM rate at the bladder neck. The median overall operative time was slightly greater in patients with ML (80 vs 75 min, P<0.001); however, there was no difference in the operative time when stratifying this result by prostate weight. Continence rates were also similar between patients with and without ML at 1 week (27.8% vs 27%, P=0.870), 4 weeks (42.3% vs 48%, P=0.136), 12 weeks (82.5% vs 86.8%, P=0.107), and 24 weeks (91.5% vs 94.1%, P=0.183) after catheter removal. Finally, the median time to recovery of continence was similar between the groups (median: 5 wks, 95% confidence interval [CI]: 4.41-5.59 vs median: 5 wks, CI 4.66-5.34; log rank test, P=0.113). CONCLUSION: The presence of a ML does not affect outcomes of RARP performed by an experienced surgeon. PMID- 22050509 TI - Mn-porphyrins as novel molecular magnetic resonance imaging contrast agents. AB - BACKGROUND AND PURPOSE: In this study, we investigated the potential of a new class of therapeutic Mn porphyrins as molecular MRI probes for prostate cancer imaging. Two compounds of different bioavailibility were investigated: Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5 +)) and Mn(III) mesotetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5 +)). These compounds have previously been shown to have adjunctive antineoplastic activity through their actions as powerful superoxide dismutase mimics, peroxynitrite scavengers, and modulators of cellular redox-based signaling pathways. Strong paramagnetic MRI contrast properties and affinity for cancer cells suggest their potential application as novel diagnostic imaging agents. MATERIALS AND METHODS: MRI experiments were performed at 7.0T on a Bruker Biospec horizontal bore scanner. All in-vivo experiments were performed on 12 C57 black mice implanted with RM-9 prostate cancer cells on the hind limb. Two mg/kg of MnTnHex-2-PyP(5 +) (n = 6) and 8 mg/kg MnTE-2-PyP(5 +) (n = 6) were administered intraperitoneally 90 minutes before imaging. All the images were collected using a volume coil and processed using Paravision 4.0. RESULTS: Phantom studies reveal remarkably high T1 relaxivity changes for both metalloporphyrins, which are twofold to threefold higher than commercially available gadolinium chelates. Observable detection limits using conventional T1-weighted MRI are in the low micromolar range for both compounds. In vivo, MR relaxation changes in prostate tumor xenografts were readily observed after a single injection of either MnTE-2-PyP(5 +) or MnTnHex-2 PyP(5 +), with tumor contrast to background ratio greatest after MnTE-2-PyP(5 +) administration. CONCLUSION: After a single dose of MnTE-2-PyP(5 +), contrast changes in prostate tumors are up to sixfold greater than in surrounding, noncancerous tissues, suggesting the potential use of this metalloporphyrin as a novel diagnostic probe for detecting prostate malignancy using MRI. PMID- 22050510 TI - Preoperative warming up exercises improve laparoscopic operative times in an experienced laparoscopic surgeon. AB - BACKGROUND AND PURPOSE: Performing warm-up exercises before athletic competition or stage performance is very common; however, most surgeons do not "warm up" before performing complex surgery. We analyzed the intraoperative effects of warming up before surgery in an experienced laparoscopic surgeon. METHODS: A retrospective review of all laparoscopic partial (LPN) and radical nephrectomies (LRN) completed by an experienced laparoscopic surgeon (RVC) were analyzed according to whether warm-up exercises were performed before surgery. Routine warm-up consisted of 15 to 20 minutes of pelvic trainer suturing exercises (forehand and backhand sutures and knot tying), using both hands. Intraoperative and postoperative parameters were examined. RESULTS: LRN and LPN subjects were well matched among the warm-up group and nonwarm-up group. Patients in the LPN warm-up group did have significantly larger tumors (3.7 cm vs 2.4 cm, P=0.02). Despite larger tumors, surgical time was significantly less in the warm-up group (227 min vs 281 min, P=0 .04), and total operating room time trended toward significance (320 min vs 371 min, P=0.0501). Similarly, in the LRN group, operative times and total operating room time was significantly less in the preoperative warm-up group (P=0.0068 and P=0.014, respectively). Intraoperative and postoperative complications, estimated blood loss, positive margin rate, warm ischemia time, length of stay, changes in hemoglobin and creatinine levels from baseline were not significantly different between the two groups. CONCLUSION: Performing warm-up exercises before complex laparoscopic surgery may improve operative times and performance in the operating room, especially for complex laparoscopic surgeries. PMID- 22050511 TI - Endoscopic assessment and prediction of prostate urethral disintegration after histotripsy treatment in a canine model. AB - BACKGROUND AND PURPOSE: Histotripsy is a nonthermal focused ultrasound technology that uses acoustic cavitation to homogenize tissue. Previous research has demonstrated that the prostatic urethra is more resistant to histotripsy effects than prostate parenchyma, a finding that may complicate the creation of transurethral resection of the prostate-like treatment cavities. The purpose of this study was to characterize the endoscopic appearance of the prostatic urethra during and after histotripsy treatment and to identify features that are predictive of urethral disintegration. MATERIALS AND METHODS: Thirty-five histotripsy treatments were delivered in a transverse plane traversing the prostatic urethra in 17 canine subjects (1-3/prostate >=1 cm apart). Real-time endoscopy was performed in the first four subjects to characterize development of acute urethral treatment effect (UTE). Serial postprocedure endoscopy was performed in all subjects to assess subsequent evolution of UTE. RESULTS: Endoscopy during histotripsy was feasible with observation of intraurethral cavitation, allowing characterization of the real-time progression of UTE from normal to frank urethral disintegration. While acute urethral fragmentation occurred in 3/35 (8.6%) treatments, frank urethral disintegration developed in 24/35 (68.5%) within 14 days of treatment. Treating until the appearance of hemostatic pale gray shaggy urothelium was the best predictor of achieving urethral fragmentation within 14 days of treatment with positive and negative predictive values of 0.91 and 0.89, respectively. CONCLUSION: Endoscopic assessment of the urethra may be a useful adjunct to prostatic histotripsy to help guide therapy to ensure urethral disintegration, allowing drainage of the homogenized adenoma and effective tissue debulking. PMID- 22050512 TI - Is there still a place for the use of nerve stimulation? AB - The introduction of nerve stimulation as a method of nerve localization sparked a new beginning in regional anesthesia. It was an epochal development akin to the utilization of ultrasound in more recent times. Many experts now consider ultrasound-guided peripheral nerve blockade to be more efficient, less painful, and more successful than landmark and nerve stimulation techniques. However, inadvertent intraneural injection continues to occur despite the widespread use of ultrasound and nerve stimulation. Both of these technologies allow for only limited elucidation of needle position relative to the target nerve and are unable to reliably identify intraneural position of the needle. This article will review the role of nerve stimulation in modern regional anesthesia techniques in light of the introduction of ultrasound technology. PMID- 22050513 TI - Diagnosis and therapy for Cushing's disease with negative dynamic MRI finding: a single-centre experience. AB - OBJECTIVE: Most patients with Cushing's disease (CD) will have evidence of an adenoma on high-resolution magnetic resonance imaging (MRI). However, a significant minority of patients with CD and biochemical hypercortisolaemia have no visible adenoma on MRI. The purpose of this study was to evaluate the diagnostic value of preoperative biochemical assessment and accuracy of MRI findings on surgical outcome. DESIGN: Retrospective data set analyses. PATIENTS AND MEASUREMENT: The clinical, endocrinological, histopathological and surgical outcomes of 24 consecutive CD patients with negative MRI findings were compared with those of 95 consecutive age- and sex-matched CD patients with pituitary adenomas on MRI. RESULTS: The total remission rate was 86.6%. Among all patients, 87 had concordant positive endocrine tests and underwent neurosurgery, while bilateral inferior petrosal sinus sampling (BIPSS) was performed in 12 and 50 other patients with negative and positive MRI, respectively. A pituitary adenoma, confirmed by pathological examination, was found in 83.3% and 93.6% of patients with negative and positive MRI, respectively. The remission rate was not different between patients with negative and positive MRI (87.5 % and 86.3%, respectively; P > 0.05) or between patients who did not undergo BIPSS with negative MRI and patients with positive MRI (P > 0.05). The remission rate of patients who underwent BIPSS with negative MRI was not different from those not undergoing BIPSS (P > 0.05). The recurrence rate was higher, although not statistically different, in patients with negative MRI compared to positive ones. CONCLUSIONS: Based on the findings outlined, MRI-negative CD may be a surgically remediable syndrome, with a pathophysiological basis that primarily involves a pituitary cause of the hypercortisolaemia. PMID- 22050514 TI - Serotonin 1A receptors, depression, and memory in temporal lobe epilepsy. AB - PURPOSE: Memory deficits and depression are common in patients with temporal lobe epilepsy (TLE). Previous positron emission tomography (PET) studies have shown reduced mesial temporal 5HT1A-receptor binding in these patients. We examined the relationships among verbal memory performance, depression, and 5HT1A-receptor binding measured with 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1 yl]ethyl-N-(2-pyridyl) cyclohexane carboxamide (18FCWAY) PET in a cross-sectional study. METHODS: We studied 40 patients (24 male; mean age 34.5 +/- 10.7 years) with TLE. Seizure diagnosis and focus localization were based on ictal video electroencephalography (EEG) recording. Patients had neuropsychological testing with Wechsler Adult Intelligence Score III (WAIS III) and Wechsler Memory Score III (WMS III) on stable antiepileptic drug (AED) regimens at least 24 h since the last seizure. Beck Depression Inventory (BDI) scores were obtained. We performed interictal PET with 18FCWAY, a fluorinated derivative of WAY 100635, a highly specific 5HT1A ligand, and structural magnetic resonance imaging (MRI) scans to estimate partial volume and plasma free fraction corrected 18FCWAY volume of distribution (V/f1). KEY FINDINGS: Hippocampal V/f1 was significantly lower in area ipsilateral than contralateral to the epileptic focus (73.7 +/- 27.3 vs. 95.4 +/- 28.4; p < 0.001). We found a significant relation between both left hippocampal 18FCWAY V/f1 (r = 0.41; p < 0.02) and left hippocampal volume (r = 0.36; p < 0.03) and delayed auditory memory score. On multiple regression, there was a significant effect of the interaction of left hippocampal 18FCWAY V/f1 and left hippocampal volume on delayed auditory memory, but not of either alone. High collinearity was present. In an analysis of variance including the side of the seizure focus, the effect of left hippocampal 18FCWAY V/f1 but not focus laterality retained significance. Mean BDI was 8.3 +/- 7.0. There was a significant inverse relation between BDI and 18FCWAY V/f1 ipsilateral to the patient's epileptic focus (r = 0.38 p < 0.02). There was no difference between patients with a right or left temporal focus. There was no relation between BDI and immediate or delayed auditory memory. SIGNIFICANCE: Our study suggests that reduced left hippocampal 5HT1A-receptor binding may play a role in memory impairment in patients with TLE. PMID- 22050515 TI - Binary Pt-Si nanostructures prepared by focused electron-beam-induced deposition. AB - Binary systems of Pt-Si are prepared by electron-beam-induced deposition using the two precursors, trimethyl(methylcyclopentadienyl)platinum(IV) (MeCpPt(Me)(3)) and neopentasilane (Si(SiH(3))(4)), simultaneously. By varying the relative flux of the two precursors during deposition, we are able to study composites containing platinum and silicon in different ratios by means of energy-dispersive X-ray spectroscopy, atomic force microscopy, electrical transport measurements, and transmission electron microscopy. The results show strong evidence for the formation of a binary, metastable Pt(2)Si(3) phase, leading to a maximum in the conductivity for a Si/Pt ratio of 3:2. PMID- 22050516 TI - Psychological therapies for chronic pelvic pain: systematic review of randomized controlled trials. AB - Chronic pelvic pain (CPP), a common cause of disability in women, is a condition best viewed in the biopsychosocial framework. Psychological interventions are frequently considered alongside medical and surgical treatments. Our objective was to evaluate the effectiveness of psychological therapies for the treatment of CPP. Electronic literature searches were conducted in Medline, Embase, PsycInfo and DARE databases from database inception to April 2010. Reference lists of selected articles were searched for further articles. The studies selected were randomized controlled trials of psychological therapies in patients with CPP compared with no treatment, standard gynecological treatment or another form of psychological therapy. Two reviewers independently selected articles without language restrictions and extracted data covering study characteristics, study quality and results. Reduction in pain, measured using visual analog scales or other measurements, was the main outcome measure. Of the 107 citations identified, four studies satisfied the inclusion criteria. Compared with no psychological intervention, therapy produced a standardized mean pain score of 3.27 [95% confidence interval (CI) -4.52 to -2.02] and 1.11 (95% CI -0.05 to 2.27) at 3 months and -3.95 (95% CI -5.35 to -2.55) and 0.54 (95% CI -0.78 to 1.86) at 6 months and greater, based on a visual analog scale score of 0-10. The current evidence does not allow us to conclude whether psychological interventions have an effect on self-reported pain scores in women with CPP. PMID- 22050517 TI - The wisdom of the body: future techniques and approaches to morphogenetic fields in regenerative medicine, developmental biology and cancer. PMID- 22050521 TI - Comparison of mesenchymal-like stem/progenitor cells derived from supernumerary teeth with stem cells from human exfoliated deciduous teeth. AB - AIMS: Dental tissue has been the focus of attention as an easily accessible postnatal tissue source of high-quality stem cells. Since the first report on the dental pulp stem cells (DPSCs) from permanent third molar teeth, stem cells from human exfoliated deciduous teeth (SHED) were identified as a population distinct from DPSCs. In this study, we compared DPSCs from supernumerary teeth and SHED in three age- and sex-matched patients. PATIENTS & METHODS: Dental samples were obtained from the three patients, who were 6 years old and male, with the parental consent of the three donors, and then isolated cells from dental pulp for comparative analysis between supernumerary DPSCs and SHED. RESULTS: Colony forming unit fibroblast levels and the proliferation rate of supernumerary DPSCs were slightly lower than that of SHED. The expression of cell surface antigens in supernumerary DPSCs and SHED were almost identical. Cells were mainly expressing endogenous mesodermal and ectodermal lineage markers. Differentiation capacity to osteogenic, adipogenic and chondrogenic lineage was similar in the SHED and supernumerary DPSCs. Migration assay revealed that both supernumerary DPSCs and SHED rapidly migrated toward wounded areas. Supernumerary DPSCs were altered in cell growth after storage for 2 years. Specially, the population doubling time of supernumerary DPSCs increased while that of SHED remained nearly unchanged. CONCLUSION: Both supernumerary teeth and deciduous teeth share many characteristics, such as highly proliferative clonogenic cells with a similar immunophenotype to that of mesenchymal stem cells, although they are inferior to SHED for long-term banking. Our findings suggest that supernumerary teeth are also easily accessible and noninvasive sources of postnatal stem cells with multipotency and regenerative capacity. PMID- 22050522 TI - Clinical implementation of a procedure to prepare bone marrow cells from cadaveric vertebral bodies. AB - AIMS: Vertebral bone marrow is a rich and easily accessible source of hematopoietic and mesenchymal stem cells that has been used to promote chimerism and transplantation tolerance in connection with cadaveric organ transplantation. The purpose of this study is to provide a detailed account of the procedure used to prepare the first five vertebral bone marrow products for infusion in conjunction with the first hand/hand-forelimb transplants performed at the University of Pittsburgh (PA, USA). MATERIALS & METHODS: The cell separation and release testing were performed at the University of Pittsburgh Cancer Institute's Hematopoietic Stem Cell Laboratory, a Good Manufacturing Practice-compliant facility accredited for clinical cell processing by the Foundation for Accreditation of Cellular Therapy (FACT) and for clinical flow cytometry by the College of American Pathologists (CAP). PMID- 22050523 TI - Combination of activated Schwann cells with bone mesenchymal stem cells: the best cell strategy for repair after spinal cord injury in rats. AB - AIM: We aim to explore the repair effect of combined cell therapy using activated Schwann cells (ASCs) and bone mesenchymal stem cells (BMSCs) in traumatic spinal cord injury (SCI) in rats. MATERIALS & METHODS: ASCs and BMSCs were used for combined transplantation to treat acute SCI in rats, both of which can be obtained from SCI patients. ASCs were obtained by prior ligation of saphenous nerve and BMSCs by flush of the marrow cavity with Dulbecco's modified Eagle's medium solution. Our experiment in vitro confirmed that ASCs promoted BMSCs to differentiate into mature neural cells. It also indicates that BMSCs hold the potential to repair CNS injury. ASCs and BMSCs were co-transplanted into the injured epicenter of spinal cord made by the New York University (NYU) impactor machine using a 10 g * 50 mm drop weight. Complete ASCs, BMSCs and Dulbecco's modified Eagle's medium were also transplanted in rats with SCI as a control. Recovery of rat's hindlimb function was serially evaluated by Basso, Beattie, Bresnahan locomotor rating scale and footprint analysis. Changes of neurological potential were recorded by nerve electrophysiologic test. Improvement in the microenvironment of the injured spinal cord was evaluated by hematoxylin and eosin staining, glial fibrillary acidic protein staining, biotinylated dextran amine anterograde tracing and electron microscopy. RESULTS: Using biotinylated dextran amine anterograde tracing, we demonstrated that there were more regenerative axons of corticospinal tract surrounding and passing through the injured cavity to the caudal cord in the ASC-BMSC co-graft group than those in the other three groups, and we also confirmed this further by quantitative analysis. Immunostaining for glial fibrillary acidic protein showed the smallest population of astrocytes in the injury epicenter in the ASC-BMSC group compared with the other three groups. Relatively complete myelin sheaths and organelles were found in the ASC-BMSC group compared with the other three groups under electron microscopy. CONCLUSION: Effective co-transplantation of ASCs and BMSCs promotes functional recovery in rats' hindlimbs and reduces the formation of glial scar, and remyelinates the injured axons as compared with the other three groups. This conclusion was also supported by the observation of immunohistochemistry staining and electron microscopy, suggesting the possible clinical application for the treatment of spinal injury. PMID- 22050524 TI - Regeneration of rodent small intestine tissue following implantation of scaffolds seeded with a novel source of smooth muscle cells. AB - AIMS: To apply an organ regeneration platform technology of autologous smooth muscle cell/biomaterial combination products, previously demonstrated to be successful for urinary tissue regeneration, to the regeneration of the small intestine. MATERIALS & METHODS: Patch and tubular constructs were implanted in rodent small intestines and histologically evaluated over a time course for evidence of regeneration of the laminarly organized neo-mucosa and muscle layers. RESULTS: Laminarly organized neo-mucosa and muscle layer bundles are demonstrated as early as 8 weeks postimplantation. CONCLUSION: An organ regeneration technology platform of autologous smooth muscle cell/biomaterial combination products can be extended to the regeneration of the small intestine. PMID- 22050525 TI - Intravenous umbilical cord mesenchymal stem cell infusion for the treatment of combined malnutrition nonunion of the humerus and radial nerve injury. AB - Nonunion and nerve injury are the most severe and common complications of bone fracture treatments. There is still no ideal therapy for these two complications. In this report, we first applied umbilical cord mesenchymal stem cell (UC-MSC) therapy to one patient with both nonunion and nerve injury, and observed the therapeutic effects. UC-MSCs were produced and expanded according to a clinical grade technique using serum-free medium enriched in human platelet lysate. Flow cytometry was performed to evaluate the purity of UC-MSCs, which were then intravenously injected. At 60 days postinjection, clinical examinations were performed to evaluate the therapeutic effects. Compared with before treatment, the patient's nerve reflex was present, and their muscle tone and strength increased, and x-ray and electromyography analysis further showed that the fracture gap disappeared and the nerve conduction velocity increased with shorter latency and higher amplitude. Furthermore, the clinical evolution was favorable and no side effects were observed during the 1-year follow-up. Overall, this novel treatment might open up a new strategy for the treatment of bone fracture complications. PMID- 22050527 TI - Urologic applications of engineered tissue. AB - Many congenital and acquired anomalies affect the genitourinary tract, necessitating surgical intervention. Among these are bladder exstrophy, hypospadias, epispadias, posterior urethral valves, myelomeningocele, bladder carcinoma, urethral stricture disease, stress urinary incontinence, pelvic organ prolapse, vesicoureteral reflux and traumatic injuries of the urinary tract. Surgical repair of these conditions often utilizes skin, oral mucosa or bowel autograft or xenograft material to replace missing tissue or to augment inadequate tissues. These materials are often sufficient to restore the basic anatomy of the organ to which they are being grafted, but they usually do not completely restore normal function. In addition, postoperative complications are common, especially in the case of bladder augmentation or neobladder creation with autologous bowel. The complications and inherent limitations of these procedures may be mitigated by the availability of alternative tissue sources. Therefore, there has been a great deal of interest in developing tissues engineered from autologous materials, such as mature bladder cells, bone marrow derived stem cells and adipose tissue. Ideally, an engineered tissue would restore or preserve the normal function of the organ it is augmenting or replacing. In addition, the engineered tissue should be nonimmunogenic to minimize rejection or foreign-body reactions. For the purposes of this article, we will focus on selection of scaffolding materials, selection of cell sources, and the current applications and potential future roles of tissue engineering in urology. PMID- 22050528 TI - Ocular epithelial transplantation: current uses and future potential. AB - Visual loss may be caused by a variety of ocular diseases and places a significant burden on society. Replacing or regenerating epithelial structures in the eye has been demonstrated to recover visual loss in a number of such diseases. Several types of cells (e.g., embryonic stem cells, adult stem/progenitor/differentiated epithelial cells and induced pluripotent cells) have generated much interest and research into their potential in restoring vision in a variety of conditions: from ocular surface disease to age-related macular degeneration. While there has been some success in clinical transplantation of conjunctival and particularly corneal epithelium utilizing ocular stem cells, in particular, from the limbus, the replacement of the retinal pigment epithelium by utilizing stem cell sources has yet to reach the clinic. Advances in our understanding of all of these cell types, their differentiation and subsequent optimization of culture conditions and development of suitable substrates for their transplantation will enable us to overcome current clinical obstacles. This article addresses the current status of knowledge concerning the biology of stem cells, their progeny and the use of differentiated epithelial cells to replace ocular epithelial cells. It will highlight the clinical outcomes to date and their potential for future clinical use. PMID- 22050529 TI - Sustained interaction: the new normal for stem cell repositories? AB - Stem cell repositories, similar to many areas in human scientific research, must balance the interests of the individuals who donate their time and samples to science with the interests of scientific progress. This article seeks to explore how sustained interaction with stem cell donors can advance key donor interests (autonomy and privacy) while also increasing the scientific utility of stem cell lines. The ability to trace stem cell lines to their respective donors - underpinned by robust informed consent - enables donors to gain access to information regarding research outcomes and the uses of their biological samples, while also supporting basic and clinical research by providing a means for quality and safety controls. Measures to recontact donors and also to enable donors to withdraw from research should be well designed to ensure donors' preferences are respected while mitigating negative consequences resulting from limited data availability or compromised sample quality. To guarantee the integrity of research while respecting donors' autonomy and preferences, stem cell repositories require a prospective approach to informed consent. PMID- 22050526 TI - Generating intestinal tissue from stem cells: potential for research and therapy. AB - Intestinal resection and malformations in adult and pediatric patients result in devastating consequences. Unfortunately, allogeneic transplantation of intestinal tissue into patients has not been met with the same measure of success as the transplantation of other organs. Attempts to engineer intestinal tissue in vitro include disaggregation of adult rat intestine into subunits called organoids, harvesting native adult stem cells from mouse intestine and spontaneous generation of intestinal tissue from embryoid bodies. Recently, by utilizing principles gained from the study of developmental biology, human pluripotent stem cells have been demonstrated to be capable of directed differentiation into intestinal tissue in vitro. Pluripotent stem cells offer a unique and promising means to generate intestinal tissue for the purposes of modeling intestinal disease, understanding embryonic development and providing a source of material for therapeutic transplantation. PMID- 22050531 TI - Peroxyesters as precursors to peroxyl radical clocks. AB - The reactions of peroxyl radicals are at the center of the oxidative degradation of essentially all petroleum-derived hydrocarbons and biological lipids and consequently, the inhibition of these processes by radical-trapping antioxidants. Recently described peroxyl radical clocks offer a simple, convenient, and inexpensive method of determining rate constants for H-atom transfer reactions to peroxyl radicals, greatly enabling the kinetic and mechanistic characterization of compounds with antioxidant properties. We follow up our preliminary communication on the development of a methodology utilizing tert-butyl styrylperacetate as a precursor to a versatile peroxyl radical clock with the present paper, wherein we describe a novel naphthyl analogue, which provides for much improved product resolution for analysis, and provide the complete details associated with its development and application. Using this new precursor, and with consideration of the expanded set of reaction products, inhibition rate constants were measured for a variety of representative phenolic and diarylamine radical-trapping antioxidants. We also provide details for the use of this methodology for the determination of mechanistic information, such as kinetic solvent effects, Arrhenius parameters, and kinetic isotope effects. PMID- 22050532 TI - Serum uric acid is related to cardiovascular events and correlates with N terminal pro-B-type natriuretic peptide and albuminuria in patients with diabetes mellitus. AB - BACKGROUND: Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes. METHODS: In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded. RESULTS: The median duration of diabetes was 11 +/- 10.35 years. Patients were in the mean 60 +/- 13 years old and mean HbA(1c) was 62 +/- 13 mmol/mol (7.8 +/- 3.3%). At baseline, mean uric acid was 321.2 +/- 101.1 MUmol/l (range 101.1-743.5 MUmol/l), median N terminal pro-B-type natriuretic peptide was 92 +/- 412 pg/ml and median urinary albumin to creatinine ratio was 8 +/- 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide (r = 0.237, P < 0.001) and urinary albumin:creatinine ratio (r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model. CONCLUSION: Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes. PMID- 22050533 TI - Signal transduction by IRE1-mediated splicing of bZIP50 and other stress sensors in the endoplasmic reticulum stress response of rice. AB - The endoplasmic reticulum (ER) stress sensor IRE1 transduces signals by inducing the unconventional splicing of mRNAs encoding key transcription factors: HAC1 in yeast and XBP1 in animals. However, no HAC1 or XBP1 homologues have been found in plants, and until recently the substrate for plant IRE1 has remained unknown. This study demonstrates that the Oryza sativa (rice) OsbZIP50 transcription factor, an orthologue of Arabidopsis AtbZIP60, is regulated by IRE1-mediated splicing of its RNA. Despite the presence of a transcriptional activation domain, OsbZIP50 protein is not translocated into the nucleus efficiently in the absence of OsbZIP50 mRNA splicing. Unconventional splicing of OsbZIP50 mRNA causes a frame shift, which results in the appearance of a nuclear localization signal in the newly translated OsbZIP50. OsbZIP50 mRNA is spliced in a similar manner to HAC1 and XBP1 mRNAs; however, this splicing has very different effects on the translation products, a finding that shows the diversity of IRE1-related transcription factors in eukaryotes. In addition, the expression of OsbZIP50 is affected by ER stress sensor proteins OsIRE1, OsbZIP39 and OsbZIP60. ER stress related genes differ with respect to their dependency on OsbZIP50 for their expression. The findings of this study improve our understanding of the molecular mechanisms underlying the plant ER stress response. PMID- 22050534 TI - Improvement of the composition of Tunisian myrtle berries (Myrtus communis L.) alcohol extracts. AB - Different extracts from myrtle berries were obtained using alcohol-water mixtures as an extraction medium in the range of 60-90% (v/v) to study the extraction efficiency in the preparation of myrtle liqueur. Flavonoids and anthocyanins were identified by high-performance liquid chromatography (HPLC) coupled with electrospray mass spectrometry and quantified during the maceration period by HPLC coupled with ultraviolet/visible detection. The antioxidant activity was tested by the 2,2-diphenyl-1-picrylhydrazyl assay. Dry matter, pH, and color parameters (L, a, b) were also analyzed. At the end of the maceration period, EE80 showed better anthocyanins stability and the highest total antioxidant activity (87.5%). These results suggest that the use of ethanol 80% provides the extract with the best characteristics for liqueur preparation. The present study contributes significantly to increase the marketing appeal of myrtle berries. PMID- 22050535 TI - Which obese youth are at increased risk for type 2 diabetes? Latent class analysis and comparison with diabetic youth. AB - PURPOSE: Most obese youth screened for diabetes have normal fasting glucose levels. Identification of youth with increased risk for type 2 diabetes (T2D) is needed within this large population to guide further management. METHODS: Retrospective chart review was performed for obese youth, 8-20 yr old, who met American Diabetes Association criteria for screening (OB) or had T2D (D). Measures included body mass index z-score (BMIz) and homeostasis model assessment of insulin resistance (HOMA-IR) by fasting plasma glucose (FPG) and insulin. Statistics compared OB with D and further examined OB by latent class analysis (LCA). RESULTS: Normal FPG was found in 91.5% of all obese youth (OBt n = 94) Comparison of OB with normal FPG (OBng; n = 86) and D (n = 44) was significant for family history of T2D (p = 0.008) without other associations. Evaluation of OBng by LCA showed three classes with increasing BMIz and HOMA-IR. Class 3 (32.5%; BMIz 2.66 +/- 0.38; HOMA-IR 6.72 +/- 2.29) differed from classes 1 and 2 (p < 0.05), and was associated with family history of T2D. CONCLUSION: Currently recommended screening of obese youth by FPG is normal in 91.5%, but lacks further information to detect increased risk for youth-onset T2D. Evaluation of obese youth by LCA identified one third (class 3) in whom the combination of higher levels of BMIz, HOMA-IR, and family history suggests the greatest risk for T2D and targets them for further evaluation and intensive preventative management. PMID- 22050536 TI - Colorectal cancer screening disparities in Asian Americans and Pacific Islanders: which groups are most vulnerable? AB - BACKGROUND: Colorectal cancer (CRC) is a significant cause of mortality among Asian Americans and Pacific Islanders (AAPIs), yet studies have consistently reported lower CRC screening rates among AAPIs than among non-Latino Whites and African Americans. Moreover, existing research tends to aggregate AAPIs as one group when reporting CRC screening, masking the disproportionate burden in cancer screening that exists across AAPI groups. METHODS: This study examines differences in CRC screening rates in both aggregated and disaggregated AAPI groups as compared with non-Latino Whites in order to identify the most vulnerable AAPI subgroups in terms of obtaining CRC screening. This study utilizes merged data from the 2001, 2003, and 2005 California Health Interview Survey (CHIS), specifically the data pertaining to adults aged 50 and older (n = 52,491) from seven AAPI groups (Chinese, Japanese, Korean, Filipino, South Asian, Vietnamese, and Pacific Islander) and non-Latino Whites. Andersen's Behavioral Model of Health Services Use was utilized to select potential confounders to racial/ethnic differences in CRC screening. RESULTS: When AAPI groups were considered as an aggregate, their CRC screening rate (46.8%) was lower than that of non-Latino Whites (57.7%). When AAPI groups were disaggregated, further disparity was noted: Koreans (32.7%) showed the lowest CRC screening rate, whereas Japanese (59.8%) had the highest. When the influence of potential predisposing, enabling, and need confounders was adjusted, Koreans, Filipinos, and South Asians were found to have a lower likelihood than non-Latino Whites to undergo CRC screening. Comparisons among AAPI subgroups further revealed that Filipinos, Koreans, Pacific Islanders, and South Asians were less likely than Chinese, Japanese, and Vietnamese to receive CRC screening. CONCLUSION: These results highlight the importance of identifying differences in CRC screening behavior among disaggregated AAPI subgroups in order to help health professionals and policy-makers prioritize which AAPI subgroups need the most urgent interventions in terms of CRC screening promotion. PMID- 22050537 TI - Use and quality of mental health services for Haitian youth. AB - OBJECTIVE: To describe the mental health service use of Haitian, African American, and non-Latino White youth in a community mental health setting. Groups are compared on adherence to treatment guidelines for attention deficit/hyperactivity disorder (ADHD) and depressive disorders. DESIGN: Retrospective review of outpatient mental health charts (n = 252) from five community sites in an urban area of the Northeastern United States. We recorded the total number and treatment type of sessions during the first six months of treatment. Guideline-adherent treatments were compared and predicted after controlling for clinical need. RESULTS: Most Haitian and African-American youth stopped treatment by six months, with the majority attending less than eight sessions. One third of Haitian and African-American patients attended just one session. Haitian patients who presented with less severe symptoms and dysfunction were more likely to have single-session treatments. Guideline-adherent treatment for ADHD and depression was less likely for Haitians. Older patients were more likely to receive adequate depression treatment. Haitian youth were relatively underinsured, had more family separations documented, and received Adjustment Disorder diagnoses more often. CONCLUSIONS: Haitian youth use outpatient mental health services in similar proportion to African-American youth and at lower rates than White youth. Guideline-adherent treatment for ADHD and depression is limited by low retention in care for Black youth. Low insurance coverage is likely an important contributor to reduced use of services, especially for Haitians. These findings are discussed in the context of providing culturally sensitive mental health care to diverse communities. PMID- 22050539 TI - The association between inflammatory bowel disease and periodontitis among Jordanians: a case-control study. AB - BACKGROUND AND OBJECTIVE: Inflammatory bowel disease (IBD) is hypothesized to involve immuno-inflammatory alterations, and the condition has been related to increased susceptibility to oral challenges. The objective of the study was to determine the association between the prevalence, severity and extent of periodontitis and both ulcerative colitis (UC) and Crohn's disease (CD). MATERIAL AND METHODS: A case-control study was conducted among patients who attended outpatient clinics at King Hussein Medical City in Jordan during the study period. All participants completed the questionnaire and underwent thorough oral and periodontal examinations. Periodontitis was defined as presence of four or more teeth with one or more sites with probing pocket depth >= 4 mm and clinical attachment level >= 3 mm. The general linear model multivariate procedure and multivariate binary logistic regression were used to analyse the data. RESULTS: This case-control study included 260 Jordanian adults (101 with UC, 59 with CD and 100 with no IBD) with a mean (SD) age of 39.4 (0.7) years. The prevalence of periodontitis was much higher among patients with CD and those with UC compared with subjects having no IBD in the age groups < 36 and 36-45 years old only. After adjusting for age and number of missing teeth, patients with CD (odds ratio 4.9, 95% confidence interval 1.8-13.2) and patients with UC (odds ratio 7.00, 95% confidence interval 2.8-17.5) had significantly higher odds of periodontitis than subjects with no IBD. In multivariate analysis, the severity of periodontitis was significantly higher among patients with CD and patients with UC when compared with subjects having no IBD. Ulcerative colitis patients but not CD patients had significantly higher prevalence of deep ulcers in oral soft tissues than the non IBD group (p = 0.004). CONCLUSION: Patients with IBD have higher prevalence, severity and extent of periodontitis compared with those having no IBD. PMID- 22050540 TI - Management of daytime urinary incontinence and lower urinary tract symptoms in children. AB - Lower urinary tract symptoms, particularly urgency, frequency and incontinence are common in school-aged children but are often overlooked. They may cause considerable physical, social and psychological difficulties to children and their families, and usually are manifestations of underlying non-neurogenic voiding disorders. The differential diagnoses include overactive bladder syndrome, dysfunctional voiding and vaginal reflux as well as less common conditions like giggle incontinence, voiding postponement, pollakiuria and diabetes insipidus. In this paper, we discuss an evidence-based approach to the management of conditions causing daytime urinary incontinence and lower urinary tract symptoms in children from a general paediatrician's perspective. PMID- 22050541 TI - Anti-inflammatory phenolics isolated from Juniperus rigida leaves and twigs in lipopolysaccharide-stimulated RAW264.7 macrophage cells. AB - Inflammation is an essential host defense system particularly in response to infection and injury; however, excessive or undesirable inflammatory responses contribute to acute and chronic human diseases. A high-throughput screening effort searching for anti-inflammatory compounds from medicinal plants deduced that the methanolic extract of Juniperus rigida S. et L. (Cupressaceae) inhibited significantly nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Activity-guided fractionation and isolation yielded 13 phenolic compounds, including one new phenylpropanoid glycosides, 3,4 dimethoxycinnamyl 9-O-beta-D-glucopyranoside (1). Among the isolated compounds, phenylpropanoid glycosides with p-hydroxy group (2, 4) and massoniaside A (7), (+)-catechin (10), amentoflavone (11) effectively inhibited LPS-induced NO production in RAW264.7 cells. PMID- 22050542 TI - CD36 c.1264 T>G null mutation impairs acquisition of IgG antibodies to Plasmodium falciparum MSP119 antigen and is associated with higher malaria incidences in Tanzanian children. AB - Polymorphisms in genes that encode crucial signalling molecules have been proposed as factors that influence susceptibility to, and outcome of malaria. We studied the role of a mutation, c.1264 T>G, that causes CD36 deficiency on IgG responses to MSP-119 antigen and malaria incidence. Children were genotyped for the c.1264 T>G mutation at the beginning of the study using PCR-RFLP. IgG levels [optical density (OD) readings] and per cent seropositivity to MSP-119 were determined at baseline by ELISA. Children were followed for 12 months for acquisition of anti-MSP-119 IgG antibody and malaria incidence. We observed a significant increase in the production of anti-MSP-119 IgG antibody in normal and heterozygous children during the 12 months of follow-up, but not in homozygous mutants. Normal children had a significantly lower malaria incidence rate compared to other genotypes (chi2 = 115.59; P < 0.01). We conclude that the presence of the c.1264 T>G mutation that leads to CD36 deficiency is closely associated with reduced IgG production and higher malaria incidence. It is most likely that deficiency of CD36 which is known to modulate dendritic cell function suppresses the production of protective IgG antibodies directed to Plasmodium falciparum MSP-119 antigen, which predisposes to the acquisition of clinical malaria in children. PMID- 22050543 TI - Using chemical reactivity to provide insights into environmental transformations of priority organic substances: the Fe0-mediated reduction of Acid Blue 129. AB - Sulfonated anthracenedione dyes are medium priority organic compounds targeted for environmental assessment under the Government of Canada's Chemical Management Plan (CMP). Since organic compounds undergo transformations in environmental matrices, understanding these transformations is critical for a proper assessment of their environmental fate. In the current study, we used zero-valent iron (ZVI) to provide insight into reductive transformation processes available to the anthracenedione dye, Acid Blue 129 (AB 129), a dye which is used in the textile industry. At high temperatures, we found that AB 129 was rapidly reduced (within 3 h) after being adsorbed onto the ZVI-surface, whereupon decomposition took place via multiple competitive and consecutive reaction pathways. Reaction products were identified using state-of-the-art accurate mass Liquid Chromatography-Quadrupole Time of Flight-Mass Spectroscopy (LC-QToF-MS). Five transformation products were identified, including a genotoxic (and thus, potentially carcinogenic) end-product, 2,4,6-trimethylaniline. The same products were found at room temperature, demonstrating that the transformation pathways revealed here could plausibly arise from biological and/or environmental reductions of AB 129. Our results demonstrate the importance of identifying reaction product arising from priority substances as part of the environmental risk assessment process. PMID- 22050544 TI - Periodontal regeneration with enamel matrix derivative in reconstructive periodontal therapy: a systematic review. AB - BACKGROUND: Enamel matrix derivative (EMD) is commonly used in periodontal therapy. The aim of this systematic review is to give an updated answer to the question of whether the additional use of EMD in periodontal therapy is more effective compared with a control or other regenerative procedures. METHODS: A literature search in MEDLINE (PubMed) for the use of EMD in periodontal treatment was performed up to May 2010. The use of EMD in treatment of intrabony defects, furcations, and recessions was evaluated. Only randomized controlled trials with >=1 year of follow-up were included. The primary outcome variable for intrabony defects was the change in clinical attachment level (CAL), for furcations the change in horizontal furcation depth, and for recession complete root coverage. RESULTS: After screening, 27 studies (20 for intrabony defects, one for furcation, and six for recession) were eligible for the review. A meta-analysis was performed for intrabony defects and recession. The treatment of intrabony defects with EMD showed a significant additional gain in CAL of 1.30 mm compared with open-flap debridement, EDTA, or placebo, but no significant difference compared with resorbable membranes was shown. The use of EMD in combination with a coronally advanced flap compared with a coronally advanced flap alone showed significantly more complete root coverage (odds ratio of 3.5), but compared with a connective tissue graft, the result was not significantly different. The use of EMD in furcations (2.6 +/- 1.8 mm) gave significantly more improvement in horizontal defect depth compared with resorbable membranes (1.9 +/- 1.4 mm) as shown in one study. CONCLUSIONS: In the treatment of intrabony defects, the use of EMD is superior to control treatments but as effective as resorbable membranes. The additional use of EMD with a coronally advanced flap for recession coverage will give superior results compared with a control but is as effective as a connective tissue graft. The use of EMD in furcations will give more reduction in horizontal furcation defect depth compared with resorbable membranes. PMID- 22050545 TI - Effectiveness of systemic amoxicillin/metronidazole as an adjunctive therapy to full-mouth scaling and root planing in the treatment of aggressive periodontitis: a systematic review and meta-analysis. AB - BACKGROUND: The systemic use of combined amoxicillin and metronidazole (AMX/MET) as an adjunctive treatment to full-mouth scaling and root planing (FMSRP) has been proposed for the treatment of generalized aggressive periodontitis; however, its effectiveness and clinical safety remain to be defined. The purpose of the present meta-analysis is to assess the effectiveness of FMSRP + AMX/MET compared to FMSRP alone. METHODS: An electronic search of eight databases and a hand search of 10 international dental journals were conducted through September 11, 2011. Gain in clinical attachment level (CAL), reduction in probing depth (PD), secondary outcomes, and adverse events were analyzed. A random-effect model was used to pool the extracted data. The weighted mean difference (MD) with 95% confidence interval (CI) was calculated for continuous outcomes, whereas risk difference (RD) with 95% CI was used for dichotomous data; heterogeneity was assessed with the chi(2)-based Cochran Q test and I(2) statistic. The level of significance was set at P <0.05. RESULTS: After the selection process, six randomized clinical trials were included. Results of the meta-analysis showed significant CAL gain (MD, 0.42; 95% CI, 0.23 to 0.61; P <0.05) and PD reduction (MD, 0.58; 95% CI, 0.39 to 0.77; P <0.05) in favor of FMSRP + AMX/MET; moreover, no significant RD was found in the occurrence of adverse events (RD, 0.01; 95% CI, -0.02 to 0.04; P >0.05). CONCLUSION: The findings of the meta-analysis seem to support the effectiveness and the clinical safety of FMSRP + AMX/MET; however, future studies are needed to confirm these results. PMID- 22050546 TI - The effects of chronic periodontitis and rheumatoid arthritis on serum and gingival crevicular fluid total antioxidant/oxidant status and oxidative stress index. AB - BACKGROUND: Chronic periodontitis (CP) and rheumatoid arthritis (RA) appear to share many pathologic features. Oxygen metabolism has an important role in the pathogenesis of both CP and RA. The aim of this study is to evaluate the relationship between these two chronic inflammatory diseases with regard to antioxidant and oxidant status. METHODS: A total of 80 participants were divided into four groups of 20 each: group RA-CP (patients with RA and CP), group RA (periodontally healthy patients with RA), group CP (systemically healthy patients with CP), and group C (periodontally and systemically healthy volunteers) were included in the study. After assessment of periodontal measurements, gingival crevicular fluid (GCF) samples were taken at one incisor, premolar, and molar tooth and stored with serum samples at -80 degrees C for the antioxidant/oxidant assay. RESULTS: Although all clinical measurements in groups RA-CP and CP were statistically higher compared to those of C and RA groups (P <0.001), there were no differences between CP and RA-CP groups (P >0.05). GCF total oxidant status (TOS) values of CP and RA-CP groups were higher than those of the RA group (P <0.05). GCF oxidative stress index (OSI) values of the RA-CP group were higher than those of the RA group (P <0.05). There were no differences among the groups in terms of serum TOS and OSI values (P >0.05). CONCLUSIONS: Local OSI values in groups with patients with CP were higher, whereas systemic OSI values showed no difference among the groups. The presence of RA seems not to affect local and systemic OSI values in patients with CP. PMID- 22050547 TI - Enamel matrix derivative promotes superoxide production and chemotaxis but reduces matrix metalloproteinase-8 expression by polymorphonuclear leukocytes. AB - BACKGROUND: Polymorphonuclear leukocyte (PMN) is the predominant innate immune cell type activated in acute inflammation. The aim of this study is to determine the impact of enamel matrix derivative (EMD) on superoxide (O(2)(-)) generation, chemotaxis, and matrix metalloproteinase-8 (MMP-8) secretion by PMN in vitro to better understand the role of EMD in surgical wound healing. METHODS: PMNs were isolated from healthy volunteers (n = 14). O(2)(-) generation was measured using a cytochrome c reduction assay. Chemotaxis was measured in a modified Boyden chamber. MMP-8 secretion was analyzed by Western blotting. A relative density method was used to determine the percentage of MMP-8 released from the PMNs in relation to the total cellular MMP-8 content. RESULTS: O(2)(-) generation was significantly elevated when PMNs were stimulated with EMD (200 MUg/mL) (P <0.01). Secondary stimulation of PMNs with 1 MUM N-formyl-methionyl-leucyl-phenylalanine (fMLP) triggered earlier and more sustained O(2)(-) generation with EMD. EMD significantly increased PMN chemotactic activity (P <0.05). Combined stimulation with EMD plus fMLP resulted in significantly higher chemotaxis compared to fMLP alone (P <0.05). Conversely, EMD did not induce MMP-8 secretion from PMNs. MMP-8 secretion by PMNs in response to fMLP or serum-opsonized zymosan stimulation was significantly inhibited by EMD (P <0.05). CONCLUSIONS: EMD has specific, differential actions on PMNs that suggest potential for enhancement of wound healing, bacterial and tissue debris clearance (O(2)(-) generation and chemotaxis), and suppression of tissue damage and degradation (MMP-8 ). Together, the data suggest that EMD enhances wound healing and reduces inflammation. PMID- 22050548 TI - Expression of the interleukin-10 signaling pathway genes in individuals with Down syndrome and periodontitis. AB - BACKGROUND: Individuals with Down syndrome (DS) have a higher prevalence and severity of periodontal disease, which cannot be explained by poor oral hygiene alone and is related to changes in the immune response. The aim of this study is to evaluate whether DS was associated with differential modulation of expression of genes associated with proinflammatory and anti-inflammatory responses in periodontal disease. METHODS: A total of 51 individuals were evaluated: 19 individuals with DS and periodontal disease (group 1), 20 euploid individuals with periodontal disease (group 2; positive control), and 12 euploid individuals without periodontal disease (group 3; negative control). Clinical periodontal evaluation and gingival biopsies were performed. Quantitative reverse transcription-polymerase chain reaction was used to determine expression levels of interleukin-10 (IL-10), the receptors IL-10RA and IL-10RB, intracellular adhesion molecule 1 (ICAM-1), interferon-gamma-inducible protein 10 (IP-10), and the signaling intermediates Janus kinase 1, signal transducer and activator of transcription 3 (STAT-3), and suppressor of cytokine signaling 3 (SOCS-3). RESULTS: Expression of IL10, SOCS3, IP10, and ICAM1 mRNA in DS patients was significantly lower compared to euploid individuals with periodontal disease, whereas IL-10RB and STAT-3 mRNA levels were higher in individuals with DS. CONCLUSION: Reduced expression of IL-10 coupled with a possible increase of STAT3 activation (increase of STAT3 and reduction of SOCS3 mRNA) indicates an important modulation of the immune response, with attenuation of anti-inflammatory and increase of proinflammatory mediators. This modulation may be related to the increased prevalence and severity of periodontitis in individuals with DS. PMID- 22050549 TI - A case of squamous cell carcinoma presenting as localized severe periodontitis in the maxillary gingiva. AB - BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the oral cavity. The clinical features of gingival SCC include alveolar bone loss and erythematous lesion. Therefore, gingival SCC sometimes presents as advanced periodontitis. This case report describes a patient diagnosed with gingival SCC after the extraction of molars presenting as being affected by localized severe periodontitis. METHODS: The patient was a 61-year-old man whose chief complaint was pain in the left maxillary area. Clinical and radiographic examinations revealed common findings of a periodontal abscess on the left maxillary first and second molars. These teeth were extracted based on a diagnosis of a periodontal abscess. Three months later, a rapidly growing exophytic soft tissue mass was observed, and a biopsy of the mass was performed. RESULTS: According to the biopsy, the final diagnosis was a well-differentiated SCC. The patient was treated with a partial maxillectomy of the left maxilla and split-thickness skin graft. Two years after treatment, the patient remained free of recurrence. CONCLUSIONS: Gingival SCC is quite different from other forms of SCC, mimicking localized periodontal disease. Therefore, it can be misdiagnosed as localized periodontal disease and is generally discovered after extracting teeth. Therefore, clinicians must diagnose these lesions carefully and follow up with the patient after tooth extraction. PMID- 22050550 TI - Peripheral catheter techniques. AB - With ultrasound, continuous peripheral nerve blocks (CPNBs) are one of the most recent developments in regional anesthesia in children. CPNBs are now used more widely in children because more suitable materials have been marketed, allowing complete, and prolonged postoperative pain control. Their use after orthopedic procedures in children and treatment for complex regional pain syndrome in adolescents has demonstrated the benefits. Perineural catheters have also shown their superiority over other techniques of continuous regional anesthesia in terms of side effects. The efficiency and the safety of these techniques may facilitate early ambulation with improved pain management, treatment at home with disposable pumps, and improved rehabilitation of children. Studies on large cohorts of patients published to date have failed to highlight any severe complications in their use compared with other adult studies. Accidents owing to systemic toxicity are very unlikely if the recommended maximum dose is not exceeded. The safety of continuous regional anesthesia techniques in children relies on the use of low-concentration l-enantiomer solutions (ropivacaine or levobupivacaine) accompanied by low plasma concentrations of local anesthetics, limiting the risk of systemic toxicity of these molecules. CPNB can ensure strong and lasting analgesia in hospital or at home. PMID- 22050551 TI - Seizure-induced miosis. AB - Ictal autonomic pupillary dilation is common; however, miosis is rare. We describe a case of focal seizures secondary to cortical dysplasia presenting with bilateral pupillary miosis, rendered seizure free by resective surgery. The seizure-onset zone was localized within the left middle parietal gyrus by intracranial electrographic recording. Seizure onset was coincident with focal left centroparietal fast spike activity on electroencephalography (EEG). A large region of the left frontocentral cortical dysplasia was demonstrated on magnetic resonance imaging (MRI). Complete resection of the area of cortical dysplasia and additional cortical regions of ictal activity, identified using intracranial EEG, rendered the patient seizure free. PMID- 22050553 TI - Does postoperative 'M' technique massage with or without mandarin oil reduce infants' distress after major craniofacial surgery? AB - AIM: This article is a report of a randomized controlled trial of the effects of 'M' technique massage with or without mandarin oil compared to standard postoperative care on infants' levels of pain and distress, heart rate and mean arterial pressure after major craniofacial surgery. BACKGROUND: There is a growing interest in non-pharmacological interventions such as aromatherapy massage in hospitalized children to relieve pain and distress but well performed studies are lacking. METHODS: This randomized controlled trial allocated 60 children aged 3-36 months after craniofacial surgery from January 2008 to August 2009 to one of three conditions; 'M' technique massage with carrier oil, 'M' technique massage with mandarin oil or standard postoperative care. Primary outcome measures were changes in COMFORT behaviour scores, Numeric Rating Scale pain and Numeric Rating Scale distress scores assessed from videotape by an observer blinded for the condition. RESULTS: In all three groups, the mean postintervention COMFORT behaviour scores were higher than the baseline scores, but differences were not statistically significant. Heart rate and mean arterial pressure showed a statistically significant change across the three assessment periods in all three groups. These changes were not related with the intervention. CONCLUSIONS: Results do not support a benefit of 'M' technique massage with or without mandarin oil in these young postoperative patients. Several reasons may account for this: massage given too soon after general anaesthesia, young patients' fear of strangers touching them, patients not used to massage. PMID- 22050552 TI - Genetic susceptibility to psoriasis and psoriatic arthritis: implications for therapy. AB - The era of genome-wide association studies has revolutionized the search for genetic susceptibility loci in complex genetic conditions such as psoriasis. There are currently 16 loci with confirmed evidence for association with psoriasis susceptibility but there is the potential for more to be discovered as the genetic heritability of the disease has not yet been fully explained. Many of the associated loci overlap with those for psoriatic arthritis. In contrast to psoriasis susceptibility, few studies have been performed to identify predictors of drug response in psoriasis. As large-scale collaborations and registries for psoriasis and psoriatic arthritis are established, it is likely that a genome wide approach may be used as a more effective method of searching for genetic predictors of treatment response. However, candidate gene studies will still have a role; for example, it is likely that some disease susceptibility genes will also be markers of treatment response, based on evidence from other diseases. This review summarizes recent advances in investigating the role genetics plays in psoriasis susceptibility and contrasts these to advances made in psoriatic arthritis. Further, it describes the genetics of treatment response in the two diseases and indicates how susceptibility loci could be used to identify drug response in the future. PMID- 22050554 TI - Adult-onset diabetes among Arabs and Jews in Israel: a population-based study. AB - AIMS: To study the age at presentation and factors associated with adult-onset diabetes (>= 20 years) among Arabs and Jews in Israel. METHODS: Participants (n = 1100) were randomly selected from the urban population of the Hadera District in Israel. The study sample was stratified into equal groups according to sex, ethnicity (Arabs and Jews) and age. Information on age at diabetes presentation, family history of diabetes, history of gestational diabetes, socio-demographic and lifestyle characteristics was obtained through personal interviews. Self reports of diabetes were compared with medical records and were found reliable (kappa = 0.87). The risk for diabetes was calculated using Kaplan-Meier survival analysis. Factors associated with diabetes in both ethnic groups were studied using Cox proportional hazard model. RESULTS: The prevalence of adult-onset diabetes was 21% among Arabs and 12% among Jews. Arab participants were younger than Jews at diabetes presentation. By the age of 57 years, 25% of Arabs had diagnosed diabetes; the corresponding age among Jews was 68 years, a difference of 11 years (P < 0.001). The greater risk for diabetes among Arabs was independent of lifestyle factors, family history of diabetes and, among women, history of gestational diabetes; adjusted hazard ratio 1.70; 95% confidence interval 1.19-2.43. CONCLUSIONS: Arabs in Israel are at greater risk for adult onset diabetes than Jews and are younger at diabetes presentation. Culturally sensitive interventions aimed at maintaining normal body weight and active lifestyle should be targeted at this population. Possible genetic factors and gene-environmental interactions underlying the high risk for diabetes among Arabs should be investigated. PMID- 22050556 TI - Discovery of amino acid motifs for thrombin cleavage and validation using a model substrate. AB - Understanding the active site preferences of an enzyme is critical to the design of effective inhibitors and to gaining insights into its mechanisms of action on substrates. While the subsite specificity of thrombin is understood, it is not clear whether the enzyme prefers individual amino acids at each subsite in isolation or prefers to cleave combinations of amino acids as a motif. To investigate whether preferred peptide motifs for cleavage could be identified for thrombin, we exposed a phage-displayed peptide library to thrombin. The resulting preferentially cleaved substrates were analyzed using the technique of association rule discovery. The results revealed that thrombin selected for amino acid motifs in cleavage sites. The contribution of these hypothetical motifs to substrate cleavage efficiency was further investigated using the B1 IgG-binding domain of streptococcal protein G as a model substrate. Introduction of a P(2) P(1)' LRS thrombin cleavage sequence within a major loop of the protein led to cleavage of the protein by thrombin, with the cleavage efficiency increasing with the length of the loop. Introduction of further P(3)-P(1) and P(1)-P(1)'-P(3)' amino acid motifs into the loop region yielded greater cleavage efficiencies, suggesting that the susceptibility of a protein substrate to cleavage by thrombin is influenced by these motifs, perhaps because of cooperative effects between subsites closest to the scissile peptide bond. PMID- 22050557 TI - Increased tear osmolarity in patients with severe cases of conjunctivochalasis. AB - PURPOSE: To evaluate and compare tear osmolarity in different grades of conjunctivochalasis. PATIENTS AND METHODS: Forty subjects divided into four groups based on grading of conjunctivochalasis by lid-paralell conjunctival fold (LIPCOF) test and tear osmolarity evaluated by TearLab osmometer. Schirmer test, tear film break up time (BUT) and vital staining were also performed. RESULTS: Patients with mild and moderate conjunctivochalasis showed similar tear osmolarity to normal subjects. A significant increase (P < 0.008) of osmolarity was found in patients with severe conjunctivochalasis. A significant increase of osmolarity was found in patients with abnormal BUT (P = 0.018) and in patients with positive lissamine-green staining (P = 0.023). No association could be elicited when results of osmolarity were compared to those of Schirmer test or when compared those of fluorescein staining to osmolarity, respectively. CONCLUSION: Hyperosmolarity of tear was reported as a fact of ocular surface inflammation. While in mild and moderate conjunctivochalasis tear osmolarity was similar to normal controls, increased osmolarity can refer to the presence of ocular surface inflammation in these patients with severe conjunctivochalasis. PMID- 22050558 TI - Avulsion injury and levator hiatal ballooning: two independent risk factors for prolapse? An observational study. AB - OBJECTIVE: To study whether avulsion and ballooning are independent risk factors for symptoms and/or signs of pelvic organ prolapse. DESIGN: Retrospective analysis of data obtained in clinical practice. SETTING: Tertiary urogynecology unit. POPULATION: Seven hundred and sixty-one consecutive women with symptoms of pelvic floor dysfunction. METHODS: Evaluation included history, vaginal examination and four-dimensional translabial ultrasound. Ultrasound analysis was performed off-line, blinded against clinical data. Hiatal dimensions were measured at the plane of minimal hiatal dimensions. Puborectalis avulsion was identified using tomographic imaging. MAIN OUTCOME MEASURES: Symptoms and objective signs of prolapse (ICS POP-Q stage 2+). RESULTS: Owing to previous surgery 156 women were excluded, leaving 605, of whom 258 (43%) had prolapse symptoms. Significant prolapse (International Continence Society Prolapse Quantification System grade 2+) was identified as follows: cystocele in 222 (37%) women, rectocele in 159 (27%) and apical in 40 (8%), while 110 (18%) had an avulsion. There was a strong association between avulsion, hiatal ballooning and symptoms/signs of prolapse (p < 0.001). On multivariable backwards stepwise logistic regression, puborectalis avulsion was associated with an increased risk of symptoms and signs of prolapse, even after allowing for the degree of levator ballooning. The presence of avulsion did not modify the relation between hiatal area and symptoms of prolapse. CONCLUSIONS: Puborectalis avulsion injury and levator hiatal ballooning are independent risk factors for symptoms and signs of prolapse. The role of avulsion in the pathogenesis of prolapse is not fully explained by its effect on hiatal dimensions. It is likely that avulsion implies not only muscular trauma but also damage to structures impossible to assess clinically or by imaging, i.e. myofascial and connective tissue. PMID- 22050559 TI - Awareness, practice and attitude to cervical Papanicolaou smear among female health care workers in Jordan. AB - The objective was to investigate Jordanian female health care workers' awareness, practice and attitude towards screening for cervical cancer. A cross-sectional, interview-based survey of 187 female health care workers (53 physicians, 92 nurses/midwives, 42 others) was conducted. Descriptive statistics were generated. A total of 187 female health care workers were interviewed. Over 80% of sexually active interviewees, with a mean age +/- SD of 36.5 +/- 9.2 years and an awareness score +/- SD of 7.91 +/- 2.8, had never undergone Papanicolaou smear testing. Nearly half of them (47.2%) were not aware that screening was available. The majority of those who had been tested (19.1%), with an awareness score +/- SD of 9.23 +/- 3.03, did so as part of a routine visit to their gynaecologist. Only 26% of the participants were aware of the availability of a vaccine against cervical cancer, of which 63% were physicians. It is concluded that the current screening programme is not effective. There is urgent need to influence women's health care providers to highlight the need for smear tests and to develop educational programmes that will target women and health care workers. PMID- 22050560 TI - Safety profile of anterior chamber paracentesis performed at the slit lamp. AB - BACKGROUND: Anterior chamber paracentesis is a valuable diagnostic tool in the management of uveitis, but may be underutilized because of concerns over its safety. We evaluated the safety profile of anterior chamber paracentesis performed at the slit lamp as an outpatient procedure. DESIGN: Retrospective, observational case series in a single tertiary centre. PARTICIPANTS: Five hundred and sixty patients with uveitis undergoing anterior chamber paracentesis. METHODS: All anterior chamber paracenteses performed at the slit lamp for diagnostic or research purposes between January 1997 and June 2009 were analysed with regard to adverse events and pipet/syringe used. Procedures were included whether carried out on undilated or dilated pupils. MAIN OUTCOME MEASURES: Adverse events and serious adverse events. RESULTS: Out of 560 paracenteses, 510 were performed with a 27-gauge fixed-needle tuberculin syringe, and 50 using an O'Rourke aqueous pipet. All patients were prescribed a short course of topical antibiotic and examined post-procedure and 1-2 weeks later. Out of 560 procedures there were four complications (0.7%). Two patients had inadvertent injection of sterile air into the anterior chamber but with spontaneous resolution and no adverse outcome (O'Rourke pipet for both). One patient had anterior lens capsule touch that was self-sealing and left a tiny localized opacity (tuberculin syringe). One patient had an allergic reaction to povidone iodine. No patients reported pain, and there were no cases of iris trauma, entry site leak, hypotony, hyphaema or endophthalmitis. CONCLUSION: Anterior chamber paracentesis can be performed safely as an outpatient procedure at the slit lamp following adequate aseptic precaution, and appropriate counselling. PMID- 22050562 TI - Rarebit perimetry: normative values and test-retest variability. AB - BACKGROUND: We aim to establish normative values and evaluate test-retest variability for the central and foveal field tests of version 4 of rarebit perimetry. DESIGN: This was a prospective study undertaken in collaboration between Tan Tock Seng Hospital, Singapore, and Singapore Polytechnic. PARTICIPANTS: Fifty-four normal subjects were recruited and included in the study. METHODS: Subjects underwent rarebit perimetry testing, studying the central and foveal fields. All subjects repeated the test within 1 month of the initial visit. The 'mean hit rates' of one eye of every subject were analysed. MAIN OUTCOME MEASURES: Mean hit rates of subjects were analysed to establish normative values for the central and foveal fields. Test-retest variability was also analysed. RESULTS: Overall normative mean hit rates were 86.3 +/- 13.95% for the central field and 91.6 +/- 6.35% for the foveal field. For every increasing year of age, we found a 0.47% decrease in the central mean hit rates (P < 0.001). Normative mean hit rate for central and foveal fields were 90.6 +/- 12.3% and 98.2 +/- 3.7% respectively, in 'young' subjects, and 81.9 +/- 15.6% and 85.0 +/- 9.0% respectively, in 'mature' subjects. We found no significant test-retest variability in the foveal field (P = 0.554). There was significant test-retest variability in the central field (P < 0.001), but the difference was a 3.5 unit mean hit rate increase, which may be clinically significant. CONCLUSIONS: Rarebit perimetry is repeatable and reliable. We have established normative values for two age groups. PMID- 22050561 TI - Treating uncorrected refractive error in adults in the developing world with autorefractors and ready-made spectacles. AB - BACKGROUND: To evaluate a method for treating uncorrected refractive error in adults in the developing world. DESIGN: Prospective, cross-sectional study in outpatient community health centres. PARTICIPANTS: Eight hundred and forty subjects aged 18 and older from rural villages in Haiti and Belize. METHODS: Undilated refractive error screening exams were conducted over a 5-day period in rural Haiti and Belize using portable autorefractors. Isometropic, spherical, ready-made spectacles were provided to patients with bilateral refractive error, astigmatism <= 1 dioptre in each eye and visual acuity worse than 6/9 in each eye. Visual acuity was measured with and without corrective spectacles. MAIN OUTCOME MEASURES: The mean visual improvement and median final visual acuity after treatment with ready-made glasses. RESULTS: Eight hundred and forty patients aged 18 and older were screened with autorefractors. One hundred and eighty-nine subjects (22.5%) were found to have visually significant bilateral refractive error. Fifty-eight per cent (110/189) of these patients met criteria for treatment with ready-made spectacles. Visual acuity improved an average of 4.2 lines in the better eye and 4.1 lines in the worse eye with corrective glasses. The median visual acuity in the better eye was 6/6 after treatment. CONCLUSION: Autorefractors and ready-made spectacles allow for effective treatment of uncorrected refractive error in adults in the developing world. PMID- 22050563 TI - Lifetime visual prognosis of patients with glaucoma. AB - BACKGROUND: To investigate the visual outcome of glaucoma patients. DESIGN: This is a retrospective study of case notes of patients who died while under follow up in a glaucoma clinic of a University Hospital in Scotland between 2006 and 2009. PARTICIPANTS: Seventy-seven patients were identified. METHODS: Data collected included type of glaucoma, coexisting pathology and best-corrected visual acuity in Snellen (converted to decimal values) for the first and final clinic visit. The final visual status was evaluated based on the best-corrected visual acuity of the better seeing eye at the last glaucoma clinic visit. Patients who had best corrected visual acuity of less than Snellen decimal 0.5 were considered not to meet the standards for driving. MAIN OUTCOME MEASURES: Snellen decimal best corrected visual acuity, fulfilment of driving standards, and eligibility for partial sight and blind registration at the last clinic visit. RESULTS: The mean ages at presentation and death were 71.8 +/- 10.3 years and 82.2 +/- 8.7 years respectively. The mean Snellen decimal best-corrected visual acuity of the better eye at presentation was 0.78, and at the final clinic visit was 0.61. At the final clinic visit, no patients were partial sight registrable, four (5.2%) were blind registrable, and 27 (35.1%) did not fulfil UK driving criteria. Glaucoma patients with other ocular pathologies were more likely to fail UK driving criteria at presentation (P = 0.02) and at last clinic visit (P = 0.03). CONCLUSION: The majority of glaucoma patients maintained good visual function at the end of their lifetime. PMID- 22050564 TI - Early intravitreal treatment of endogenous bacterial endophthalmitis. AB - BACKGROUND: There are currently no standardized treatment guidelines for endogenous bacterial endophthalmitis. We report the long-term outcomes of early intravitreal treatment of endogenous bacterial endophthalmitis, defined as intravitreal and systemic antibiotics administered within 24 h of diagnosis, with conservative use of pars plana vitrectomy. DESIGN: Interventional retrospective case series. PARTICIPANTS: Consecutive patients treated for culture-proven endogenous bacterial endophthalmitis between 2001 and 2008 at the Weill Cornell Medical Center. METHODS: The clinical records of 18 eyes from 13 patients were reviewed. MAIN OUTCOME MEASURES: Visual acuity. RESULTS: Mean age at presentation was 61 (25-85) years. All patients had underlying medical conditions. Extraocular infectious foci were identified in nine (69%) patients, with endocarditis being the most common. Gram-positive organisms were identified in 12 (92%) patients, including five with methicillin-resistant Staphylococcus aureus. No cases were misdiagnosed. Final visual acuities of better than 6/120 and counting fingers were achieved in 6 (55%) and 7 (64%) of 11 eyes, respectively. Longer time between onset of ocular symptoms and intravitreal antibiotic injection correlated with worse visual outcomes (P < 0.05) and was associated with mortality (P < 0.05). Mortality was also associated with methicillin-resistant S. aureus infection (P < 0.05). Of those with follow up longer than 1 year, retinal detachment developed in 3 of 10 eyes (30%) after the acute infection, and cataract developed in 6 of 9 (67%) phakic eyes. Mean follow up was 146 (4-313) weeks. CONCLUSIONS: Intravitreal antibiotics for endogenous bacterial endophthalmitis administered within 24 h to supplement immediate systemic antibiotics may provide a relatively favourable visual prognosis. PMID- 22050565 TI - Geldanamycin is effective in the treatment of herpes simplex virus epithelial keratitis in a rabbit model. AB - BACKGROUND: To evaluate the efficacy of geldanamycin eye drops against herpes simplex virus epithelial keratitis in a rabbit model. METHODS: New Zealand white rabbits were randomized into four groups and infected with herpes simplex virus type 1; geldanamycin topical eye drops was initiated 24 h after the infection and maintained for 12 consecutive days. Four groups of rabbits received 5 ug/mL geldanamycin, 10 ug/mL geldanamycin, 0.1% acyclovir and escipient (a kind of artificial tears), respectively. The severity of herpes simplex virus type 1 epithelial keratitis was measured by slit-lamp and scored for statistics analysis. The virus shedding in eye swabs was isolated, and tissue culture infective dose (TCID50) was determined. RESULTS: Geldanamycin (10 ug/mL) treatment reduced significantly the severity of herpes simplex virus type 1 epithelial keratitis than the other three groups. Geldanamycin (5 ug/mL) was as effective as acyclovir (0.1%) treatment. The effect of geldanamycin against herpes simplex virus type 1 epithelial keratitis correlated with accelerated clearance of virus of the rabbits. CONCLUSION: Geldanamycin is a promising treatment option against herpes simplex virus type 1 epithelial keratitis. Geldanamycin (10 ug/mL) is better than acyclovir and geldanamycin (5 ug/mL) in the rabbit model. The optimal concentration of this drug in human is still to be determined. PMID- 22050566 TI - Downregulation of c-Myc in pterygium and cultured pterygial cells. AB - BACKGROUND: The aim of this study was to determine c-Myc expression in pterygial tissue and in cultured fibroblasts and epithelial cells of pterygia, using normal human conjunctival samples as a control. METHODS: Expression of c-Myc in pterygium and normal human conjunctiva tissue was examined by immunohistochemical assay and Western blot. Fibroblasts and epithelial cells from primary pterygium and normal human conjunctiva were cultured in medium with or without transforming growth factor beta1 for up to 3 days. c-Myc protein expression was analysed by indirect immunofluorescence. Levels of c-Myc mRNA in fibroblasts were measured by reverse transcription polymerase chain reaction. RESULTS: c-Myc protein expression was reduced in human pterygial tissue compared with normal human conjunctiva in immunohistochemical staining. The decrease was further verified by Western blot analysis. In primary cultured cells c-Myc expression as stained by immunofluorescence was reduced in both pterygial epithelial and fibroblast cells when compared with cultured normal human conjunctiva cells. In addition, compared with cells from normal conjunctiva, reduced levels of c-Myc mRNA were observed in both cultured pterygial epithelial and fibroblast cells. Increased c-Myc expression in pterygial cells, but not in normal conjunctival cells, was found when the cultured cells were treated with transforming growth factor beta1. This increase of c-Myc mRNA appeared to be time and transforming growth factor beta1 dose dependent. CONCLUSIONS: c-Myc expression is reduced in pterygium compared with normal conjunctiva. Transforming growth factor beta1 can elevate the downregulated c-Myc in cultured pterygial cells. PMID- 22050567 TI - 3-D spheroid culture of bone marrow mesenchymal stem cell of rhesus monkey with improved multi-differentiation potential to epithelial progenitors and neuron in vitro. AB - BACKGROUND: Bone mesenchymal stem cells are an attractive source of cells with potential applications in ocular regenerative medicine. However, the low differentiation efficiency in the traditional two-dimensional (2-D) culture system limits their application for clinical therapy. Here, we describe a simple and innovative 3-D culture environment and assess the potential for bone mesenchymal stem cells to differentiate into a variety of cell types in the 3-D system. METHODS: Bone mesenchymal stem cells of rhesus monkey were isolated and cultured using a density gradient centrifugation and adherence screening method. Cells at passage three were cultured by hanging drop and formed spheres. After 3 days, the spheres were collected and plated onto culture plates and maintained in a floating state by a rotary method for 10 days. Under appropriate induction conditions, the sphere cells were induced into adipocytes, osteoblasts, epithelial progenitors and neuronal cells. Differentiated cells were identified by histochemical staining, immunofluorescence and reverse transcription polymerase chain reaction. RESULTS: Bone mesenchymal stem cells of rhesus monkey in the 3-D spheroid culture system acquired improved efficient multipotency for not only adipogenic and osteogeneic differentiation, but ectodermal epithelial progenitor-like cells and neuron-like cells compared with the 2-D culture system. CONCLUSION: Our 3-D spheroid culture system provides a useful technique to gain insight into the mechanisms of bone mesenchymal stem cells differentiation, and may have potential applications for the treatment of ocular surface and optic nerve disease. PMID- 22050568 TI - Mathematics of Zernike polynomials: a review. AB - Monochromatic aberrations of the eye principally originate from the cornea and the crystalline lens. Aberrometers operate via differing principles but function by either analysing the reflected wavefront from the retina or by analysing an image on the retina. Aberrations may be described as lower order or higher order aberrations with Zernike polynomials being the most commonly employed fitting method. The complex mathematical aspects with regards the Zernike polynomial expansion series are detailed in this review. Refractive surgery has been a key clinical application of aberrometers; however, more recently aberrometers have been used in a range of other areas ophthalmology including corneal diseases, cataract and retinal imaging. PMID- 22050569 TI - Recurrent orbital inflammation in a patient with multiple sclerosis treated with interferon-beta. PMID- 22050570 TI - Bilateral acute angle-closure glaucoma as the presenting feature of a systemic leukocytoclastic vasculitis. PMID- 22050571 TI - Projected needs for eye-care services in indigenous Australians. PMID- 22050572 TI - Diabetes and its ocular complications in Timor-Leste. PMID- 22050575 TI - Genomic insights into microbial iron oxidation and iron uptake strategies in extremely acidic environments. AB - This minireview presents recent advances in our understanding of iron oxidation and homeostasis in acidophilic Bacteria and Archaea. These processes influence the flux of metals and nutrients in pristine and man-made acidic environments such as acid mine drainage and industrial bioleaching operations. Acidophiles are also being studied to understand life in extreme conditions and their role in the generation of biomarkers used in the search for evidence of existing or past extra-terrestrial life. Iron oxidation in acidophiles is best understood in the model organism Acidithiobacillus ferrooxidans. However, recent functional genomic analysis of acidophiles is leading to a deeper appreciation of the diversity of acidophilic iron-oxidizing pathways. Although it is too early to paint a detailed picture of the role played by lateral gene transfer in the evolution of iron oxidation, emerging evidence tends to support the view that iron oxidation arose independently more than once in evolution. Acidic environments are generally rich in soluble iron and extreme acidophiles (e.g. the Leptospirillum genus) have considerably fewer iron uptake systems compared with neutrophiles. However, some acidophiles have been shown to grow as high as pH 6 and, in the case of the Acidithiobacillus genus, to have multiple iron uptake systems. This could be an adaption allowing them to respond to different iron concentrations via the use of a multiplicity of different siderophores. Both Leptospirillum spp. and Acidithiobacillus spp. are predicted to synthesize the acid stable citrate siderophore for Fe(III) uptake. In addition, both groups have predicted receptors for siderophores produced by other microorganisms, suggesting that competition for iron occurs influencing the ecophysiology of acidic environments. Little is known about the genetic regulation of iron oxidation and iron uptake in acidophiles, especially how the use of iron as an energy source is balanced with its need to take up iron for metabolism. It is anticipated that integrated and complex regulatory networks sensing different environmental signals, such as the energy source and/or the redox state of the cell as well as the oxygen availability, are involved. PMID- 22050574 TI - IL-10 contributes to the suppressive function of tumour-associated myeloid cells and enhances myeloid cell accumulation in tumours. AB - Studies have revealed that tumour-associated myeloid cells (TAMC) are one of the major sources of IL-10 in tumour-bearing mice. However, the significance of TAMC derived IL-10 in tumour immunity is poorly understood. Here, we show that IL-10 blockade or IL-10 deficiency reduces the capacity of TAMC in suppressing the proliferation of P1A-specific CD8 T cells. In the spleen, IL-10-deficient and wild-type (WT) mice bearing large tumour burdens have similar TAMC populations. The tumours from IL-10-deficient mice, however, have reduced numbers of TAMC compared with tumours from their WT counterparts. IL-10-/- RAG-2-/- mice also had reduced numbers of TAMC compared with tumours from IL-10+/+ RAG-2-/- mice; therefore, the reduction in TAMC in IL-10-deficient tumours was not because of adaptive immune response in tumours. Adoptively transferred tumour antigen specific CD8 T cells expanded more efficiently within tumours in IL-10-/- RAG-2-/ mice than in tumours from IL-10+/+ RAG-2-/- mice. Cytotoxic T lymphocyte adoptive transfer therapy prevented tumour evasion in IL-10-/- RAG-2-/- mice more efficiently than in IL-10+/+ RAG-2-/- mice. Thus, IL-10 enhances the accumulation of myeloid cells in tumours, and TAMC-derived IL-10 suppresses the activation and expansion of tumour antigen-specific T cells. PMID- 22050576 TI - The cellular language of myo-inositol signaling. AB - The simple polyol, myo-inositol, is used as a building block of a cellular language that plays various roles in signal transduction. This review describes the terminology used to denote myo-inositol-containing molecules, with an emphasis on how phosphate and fatty acids are added to create second messengers used in signaling. Work in model systems has delineated the genes and enzymes required for synthesis and metabolism of many myo-inositol-containing molecules, with genetic mutants and measurement of second messengers playing key roles in developing our understanding. There is increasing evidence that molecules such as myo- inositol(1,4,5)trisphosphate and phosphatidylinositol(4,5)bisphosphate are synthesized in response to various signals plants encounter. In particular, the controversial role of myo-inositol(1,4,5)trisphosphate is addressed, accompanied by a discussion of the multiple enzymes that act to regulate this molecule. We are also beginning to understand new connections of myo-inositol signaling in plants. These recent discoveries include the novel roles of inositol phosphates in binding to plant hormone receptors and that of phosphatidylinositol(3)phosphate binding to pathogen effectors. PMID- 22050577 TI - Urinary tubular biomarkers as potential early predictors of renal allograft rejection. AB - Confirmation of kidney transplant rejection still requires a histological diagnosis on renal allograft biopsy. Research continues for new non-invasive means for early diagnosis and treatment of kidney allograft rejection. Examination of the urine in renal transplant recipients provides a logical and readily accessible non-invasive window on allograft function, reflecting the function of the kidney in its transplanted environment. Renal tubular epithelial cells (TEC) respond dynamically to the surrounding microenvironment and play an important role in allograft survival. Proteins released from TEC into the urine potentially serve as biomarkers for the early diagnosis of graft dysfunction and rejection. Activated proximal TEC express human leucocyte antigens and co stimulatory molecules, transiently transforming into non-professional antigen presenting cells that augment renal allograft rejection. Chemokines and chemoattractants expressed on proximal tubules may also facilitate the migration of alloreactive lymphocytes to local site of injury and stimulate cytokine release from infiltrating lymphocytes. Proximal TEC are also potential targets for circulating alloreactive antibodies and complement leading to cell damage. Changes in cell state during development, regeneration or immune response require a rapid modulation of both surface protein expression and secretion, altering the repertoire of proteins secreted or expressed at the TEC plasma membrane. Due to the proximity of TEC to the tubular lumen, these proteins are passed into the urine. In this regard, TEC possess a unique anatomic location within the transplanted organ and are therefore ideal indicators of graft function. Hence, measurement of the changes of TEC-derived molecules in the urine, in response to different challenges or modification, may predict graft outcome. PMID- 22050578 TI - Rheumatic fever in New Zealand. AB - Acute rheumatic fever and its sequel rheumatic heart disease remain major unsolved problems in New Zealand, causing significant morbidity and premature death. The disease burden affects predominantly indigenous Maori and Pacific Island children and young adults. In the past decade these ethnic disparities are even widening. Secondary prophylaxis using 28-day intramuscular penicillin has been the mainstay of disease control. In the greater Auckland region, audit shows community nurse-led penicillin delivery rates of 95% and recurrence rates of less than 5%. The true penicillin failure rate of 0.07 per 100 patient years supports 4 weekly penicillin rather than more frequent dose regimens. Landmark primary prevention research has been undertaken supporting sore throat primary prevention programmes in regions with very high rheumatic fever rates. Echocardiographic screening found 2.4% previously undiagnosed rheumatic heart disease in socially disadvantaged children. Combined with secondary prevention, echocardiography screening has the potential to reduce the prevalence of severe rheumatic heart disease. PMID- 22050580 TI - A significant milestone for palliative care: imperative for dissemination and implementation research. PMID- 22050581 TI - Is routinely ascertaining preferred place of death for hospice patients possible or desirable? PMID- 22050582 TI - Considerations of quality-adjusted life-year in palliative care for the terminally ill. PMID- 22050583 TI - Bedside ultrasound: a radiologic boon for placement of complex nerve blocks for abdominal malignancies. PMID- 22050584 TI - Physicians and prayer requests #120. PMID- 22050585 TI - Screening for opioid misuse and abuse #244. PMID- 22050586 TI - Living with the late effects of irradiation treatment: a physician as a cancer of the neck patient perspective. PMID- 22050587 TI - A family's struggle. PMID- 22050588 TI - Come home sweetheart: a fight for my father's last wish. PMID- 22050589 TI - A fight to the end. PMID- 22050592 TI - In vitro enzymatic response of Turkish native chicken "Gerze" to heavy metal exposure. AB - Glucose-6-phosphate dehydrogenase (G6PD) was purified and characterized from the Turkish native chicken, Gerze, erythrocytes for the first time, and some characteristics were investigated. Purification procedure consisted of ammonium sulphate fractionation and affinity chromatography on 29, 59-ADP Sepharose-4B. The enzyme was purified 1063.22-fold with a yield of 43.27% and specific activity of 93.5 EU/mg proteins. Kinetic parameters of the enzyme were determined with glucose-6-phosphate (G6P) as substrate and purified enzyme had an apparent K(M) and V(max) values of 0.222 mM and 0.097 U/ml, respectively. The same parameters were determined with NADP(+) and the K(M) and V(max) values were 0.0603 mM and 0.153 U/ml, respectively. The following metals, Cd(+2), Pb(+2), Hg(+2), Cu(+2), Zn(+2) and Fe(+3) showed inhibitory effects on the enzyme. Cd(+2) and Pb(+2) exhibited the strongest inhibitory action. Hg(+2) and Cu(+2) were moderate inhibitors, whereas Zn(+2) and Fe(+3) showed weaker actions. All tested metals inhibited the enzyme in competitive manner. PMID- 22050593 TI - CD57 and gammadelta T-cell receptor expression in nodal metastatic spread of melanoma. PMID- 22050594 TI - Patient and nurse staffing characteristics associated with high sitter use costs. AB - AIM: This paper is a report of a study of the relationships between patient health conditions, nurse staffing characteristics and high sitter use costs. BACKGROUND: Increasing recourse to patient sitters is a major cost concern to hospitals. To reduce these expenses, we need to understand better the factors associated with high sitter use costs. METHODS: From a cohort of 43,212 medical/surgical patients admitted to an academic health centre in Montreal (Canada) in 2007 and 2008, all 1151 patients who received a sitter were selected. We applied multivariate logistic regression, using the Generalized Estimating Equation framework, to estimate the relationships between patient health conditions, nurse staffing characteristics and being in the upper two quintiles of sitter costs, vs. the lower three. RESULTS: The median sitter cost per patient, in Canadian dollars, was $772.35 (IQR = $1737.84); and $2397.00 (IQR = $3085.03) among the patients with high sitter use costs. In multivariate analyses, dementia, delirium and other cognitive impairments (OR = 1.49; 95% CI = 1.01-2.22) and schizophrenia and other psychoses (OR = 2.42; 95% CI = 1.08-5.76) increased the likelihood of high sitter use costs. In addition, every additional worked hour per patient per day by Registered Nurses (OR =0.33; 95% CI = 0.27 0.39) and by patient care assistants (OR = 0.11; 95% CI = 0.08-0.15) reduced the likelihood of high sitter use costs. Conclusion. Circumstances of understaffing and patients having psycho-geriatric conditions are associated with high sitter use costs. Improving staffing and providing additional resources to support the care of psycho-geriatric patients may lower these expenses. PMID- 22050595 TI - Two structurally similar fungal prions efficiently cross-seed in vivo but form distinct polymers when coexpressed. AB - HET-s is a prion protein of the filamentous fungus Podospora anserina. An orthologue of this protein, called FgHET-s has been identified in Fusarium graminearum. The region of the FgHET-s protein corresponding to the prion forming domain of HET-s, forms amyloid fibrils in vitro. These fibrils seed HET-s(218 289) fibril formation in vitro and vice versa. The amyloid fold of HET-s(218-289) and FgHET-s(218-289) are remarkably similar although they share only 38% identity. The present work corresponds to the functional characterization of the FgHET-s(218-289) region as a prion forming domain in vivo. We show that FgHET s(218-289) is capable of prion propagation in P. anserina and is able to substitute for the HET-s PFD in the full-length HET-s protein. In accordance with the in vitro cross-seeding experiments, we detect no species barrier between P. anserina and F. graminearum PFDs. We use the yeast Saccharomyces cerevisiae as a host to compare the prion performances of the two orthologous PFDs. We find that FgHET-s(218-289) leads to higher spontaneous prion formation rates and mitotic prion stability than HET-s(218-289). Then we analysed the outcome of HET-s(218 289)/FgHET-s(218-289) coexpression. In spite of the cross-seeding ability of HET s(218-289) and FgHET-s(218-289), in vivo, homotypic polymerization is favoured over mixed fibril formation. PMID- 22050596 TI - I-THM formation and speciation: preformed monochloramine versus prechlorination followed by ammonia addition. AB - An increasing number of utilities in the United States have been switching from chlorination to chloramination practices to comply with the more stringent trihalomethane (THM) and haloacetic acid (HAA) regulations. This has important implications for disinfection byproduct (DBP) formation because the reactions of chlorine and monochloramine (NH(2)Cl) with natural organic matter (NOM) are not the same. In this study, iodinated trihalomethane (I-THM) formation from preformed NH(2)Cl and prechlorination (at two chlorine doses and contact times) followed by ammonia addition was compared. A representative bromide/iodide ratio of 10:1 was selected and four bromide/iodide levels (ambient, 50/5 or 100/10, 200/20, and 800/80 [MUg/L/MUg/L]) were evaluated. The results showed that I-THM formation was generally lower for prechlorination as compared to preformed NH(2)Cl due to the oxidation of iodide to iodate by chlorine. However, while prechlorination minimized iodoform (CHI(3)) formation, prechlorination sometimes formed more I-THMs as compared to preformed NH(2)Cl due to a large increase in the formation of brominated I-THM species, which were formed at much smaller amounts from preformed NH(2)Cl. I-THM concentrations and speciation for the two chloramination scenarios (i.e., preformed NH(2)Cl vs prechlorination followed by ammonia) depended on chlorine dose, contact time, bromide/iodide concentration, and NOM characteristics of the source water (SUVA(254)). PMID- 22050597 TI - Translating clinical activity and gene expression signatures of etanercept and ciclosporin to the psoriasis xenograft SCID mouse model. AB - BACKGROUND: The psoriasis xenograft severe combined immunodeficiency (SCID) mouse model is used in drug discovery to obtain preclinical proof-of-principle of new antipsoriatic drug candidates. Validation of this model by antipsoriatic therapeutic agents in clinical use is important to understand its utility as well as its limitations. The effects of the clinically efficacious antitumour necrosis factor-alpha biologics have not yet been demonstrated in the psoriasis xenograft SCID mouse model. OBJECTIVES: To investigate the effect of etanercept and to explore the time-dependent changes induced by ciclosporin on psoriatic biomarkers at the gene expression level in the psoriasis xenograft SCID mouse model. METHODS: Xenografted SCID mice were treated either with etanercept and vehicle for 2 weeks or with ciclosporin and vehicle for 2 and 4 weeks, respectively. Treatment-induced changes in the psoriatic grafts were assessed by gene expression analysis and compared with published clinical microarray data. The grafts were further evaluated by histology and immunohistochemistry. RESULTS: Etanercept induced normalization of gene expression, which correlated with a significant reduction in epidermal thickness as well as a decrease in the number of proliferative cells. Anti-inflammatory activity induced by ciclosporin preceded the reduction in epidermal hyperplasia. Comparison of the etanercept- and ciclosporin-induced gene expression signatures with clinical microarray data showed significant correlations. CONCLUSIONS: Efficacy of etanercept and ciclosporin could be translated to the psoriasis xenograft SCID mouse model. PMID- 22050598 TI - Native chemical ligation of hydrolysis-resistant 3'-peptidyl-tRNA mimics. AB - Hydrolysis-resistant 3'-peptidyl-RNA conjugates that mimic tRNA termini represent a remarkable synthetic challenge, particularly if they contain amino acids with complex side-chain functionalities, such as arginines. Here we demonstrate a novel approach that combines solid-phase synthesis and bioconjugation to obtain these derivatives with high efficiency and purity. The key step is native chemical ligation of 3'-cysteinyl-RNA fragments to highly soluble peptide thioesters. The so-prepared 3'-peptidyl-RNA conjugates relate to resistance peptides that can render the ribosome resistant to macrolide antibiotics by a yet unknown ribosomal translation mechanism. PMID- 22050599 TI - Availability of insulin pump therapy in clinical practice. AB - AIM: To examine the availability of insulin pump therapy in patients with Type 1 diabetes. METHODS: Patients using insulin pumps among a cohort of 7224 patients with Type 1 diabetes were studied. RESULTS: In logistic regression, used to evaluate variables not changing over time among the total cohort, use of insulin pumps varied by outpatient clinic (P<0.001) and sex (P<0.001). Cox regression analysis in 5854 patients with detailed patient data prior to use of an insulin pump showed higher HbA(1c) (P<0.0001), lower creatinine (P=0.002), high and low insulin doses (P<0.0001), younger age (P<0.0001) and female sex (P<0.0001) to be associated with use of an insulin pump. Women were 1.5-fold more likely to start using an insulin pump (hazard ratio 1.52, 95% confidence interval 1.29-1.79) and patients in the 20- to 30-years age range were more than twice as likely to begin use of an insulin pump than patients aged 40-50 years (hazard ratio 8.63, 95% confidence interval 5.91-12.59 and hazard ratio 3.98, 95% confidence interval 2.80-5.64, respectively). A 10-MUmol/l higher level of creatinine was associated with a hazard ratio of 0.56 (95% confidence interval 0.39-0.81) of starting use of an insulin pump. CONCLUSIONS: At 10 hospital outpatient clinics in Sweden, use of insulin pumps therapy varied by clinic. A higher proportion of women began using insulin pumps. Younger patients and patients with fewer complications were also more likely to start using an insulin pump. Further research is needed to confirm these findings in other geographical regions and to understand whether the availability of insulin pumps today is optimized. PMID- 22050601 TI - Identification and potency of cyclodextrin-lipid inhibitors of Staphylococcus aureus alpha-toxin. AB - PURPOSE: Staphylococcus aureus, a leading cause of bacterial keratitis, secretes alpha-toxin, a cytotoxin active on the corneal epithelium. This study describes the production and testing of chemical inhibitors of alpha-toxin action. METHODS: Purified alpha-toxin was titered by its ability to lyse rabbit erythrocytes in buffered saline (PBS). To prepare potential toxin inhibitors, each of 18 lipids was incorporated into a complex with methyl-beta-cyclodextrin (MbetaCD) or hydroxypropyl-beta-cyclodextrin (HPbetaCD). Serial dilutions of each lipid cyclodextrin (CD-lipid) complex were mixed with alpha-toxin prior to the addition of rabbit erythrocytes. Select CD-lipid complexes were mixed with 12 hemolytic units (HU) alpha-toxin and injected into the rabbit corneal stroma so the resulting corneal erosions could be measured at 4 and 8 hours post-injection (PI). Eyes injected with toxin alone, MbetaCD, or HPbetaCD alone served as controls. RESULTS: Neither form of CD alone inhibited alpha-toxin. Of the 36 complexes prepared, 6 lipid-CD complexes were found to inhibit >100 HU of alpha toxin. Four lipid complexes able to inhibit >200 HU of alpha-toxin were tested in toxin-injected corneas; at 4 and 8 hours PI, the complexes of cholesterol or lanosterol with MbetaCD and squalene or desmosterol with HPbetaCD caused a significant reduction in the corneal erosion size as compared to eyes injected with alpha-toxin alone (P <= 0.05). CONCLUSIONS: Specific lipid inclusion complexes with either MbetaCD or HPbetaCD demonstrated a significant inhibition of alpha-toxin in both in vitro and in vivo assays. Changes in either the cyclodextrin or lipid of a complex affected the inhibitory activity. PMID- 22050600 TI - Induced fit or conformational selection? The role of the semi-closed state in the maltose binding protein. AB - A full characterization of the thermodynamic forces underlying ligand-associated conformational changes in proteins is essential for understanding and manipulating diverse biological processes, including transport, signaling, and enzymatic activity. Recent experiments on the maltose binding protein (MBP) have provided valuable data about the different conformational states implicated in the ligand recognition process; however, a complete picture of the accessible pathways and the associated changes in free energy remains elusive. Here we describe results from advanced accelerated molecular dynamics (aMD) simulations, coupled with adaptively biased force (ABF) and thermodynamic integration (TI) free energy methods. The combination of approaches allows us to track the ligand recognition process on the microsecond time scale and provides a detailed characterization of the protein's dynamic and the relative energy of stable states. We find that an induced-fit (IF) mechanism is most likely and that a mechanism involving both a conformational selection (CS) step and an IF step is also possible. The complete recognition process is best viewed as a "Pac Man" type action where the ligand is initially localized to one domain and naturally occurring hinge-bending vibrations in the protein are able to assist the recognition process by increasing the chances of a favorable encounter with side chains on the other domain, leading to a population shift. This interpretation is consistent with experiments and provides new insight into the complex recognition mechanism. The methods employed here are able to describe IF and CS effects and provide formally rigorous means of computing free energy changes. As such, they are superior to conventional MD and flexible docking alone and hold great promise for future development and applications to drug discovery. PMID- 22050603 TI - Yearly diagnostic yield of colonoscopy in patients age 80 years or older, with a special interest in colorectal cancer. AB - AIM: A high diagnostic yield of colonoscopy has been reported in elderly patients, but there is no data on the yearly yield. Our aim was to detect the yearly yield of colonoscopy in elderly patients. METHODS: All consecutive endoscopies in the years 1992-2009 were included. Important endoscopic diagnoses were defined as colorectal cancer (CRC), polyps, diverticuli and inflammation. RESULTS: In total, 19 569 endoscopies were performed, of which 1706 (8.7%) were in patients age 80 years or older. The number of women was significantly higher (P < 0.001). The percentage of patients who were 80 years or older was higher than in the general population and remained stable during the study period, though there has been a proportional increase of elderly people in the general population. Inconclusive procedures were present in 106 (6.2%) elderly patients compared with 277 (1.6%) patients under 80 years of age (P < 0.001). There were no significant changes in the consecutive years. A procedure revealing no endoscopic diagnosis was observed less often in patients who were 80 years or older (P < 0.001). CRC was diagnosed in 221 (19.6%) older patients. This figure remained more or less constant each year. Polyps were seen in 448 (8.8%) patients 80 years of age or older. The percentage of patients with diverticuli and inflammation was constant. The number of patients 80 years or older with CRC and polyps rose at a lower rate than the number of older people in the general population. CONCLUSION: The yield of colonoscopy in patients 80 years or older was high and constant over the years. The number of tumors rose less than expected compared to the increase of elderly in the general population. PMID- 22050602 TI - Determination of the human cardiomyocyte mRNA and miRNA differentiation network by fine-scale profiling. AB - To gain insight into the molecular regulation of human heart development, a detailed comparison of the mRNA and miRNA transcriptomes across differentiating human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts was performed. Gene ontology analysis of the mRNA expression levels of the hiPSCs differentiating into cardiomyocytes revealed 3 distinct groups of genes: pluripotent specific, transitional cardiac specification, and mature cardiomyocyte specific. Hierarchical clustering of the mRNA data revealed that the transcriptome of hiPSC cardiomyocytes largely stabilizes 20 days after initiation of differentiation. Nevertheless, analysis of cells continuously cultured for 120 days indicated that the cardiomyocytes continued to mature toward a more adult-like gene expression pattern. Analysis of cardiomyocyte-specific miRNAs (miR-1, miR-133a/b, and miR 208a/b) revealed an miRNA pattern indicative of stem cell to cardiomyocyte specification. A biostatistitical approach integrated the miRNA and mRNA expression profiles revealing a cardiomyocyte differentiation miRNA network and identified putative mRNAs targeted by multiple miRNAs. Together, these data reveal the miRNA network in human heart development and support the notion that overlapping miRNA networks re-enforce transcriptional control during developmental specification. PMID- 22050604 TI - S1 domain-containing STF modulates plastid transcription and chloroplast biogenesis in Nicotiana benthamiana. AB - * In this study, we examined the biochemical and physiological functions of Nicotiana benthamiana S1 domain-containing Transcription-Stimulating Factor (STF) using virus-induced gene silencing (VIGS), cosuppression, and overexpression strategies. * STF : green fluorescent protein (GFP) fusion protein colocalized with sulfite reductase (SiR), a chloroplast nucleoid-associated protein also present in the stroma. Full-length STF and its S1 domain preferentially bound to RNA, probably in a sequence-nonspecific manner. * STF silencing by VIGS or cosuppression resulted in severe leaf yellowing caused by disrupted chloroplast development. STF deficiency significantly perturbed plastid-encoded multimeric RNA polymerase (PEP)-dependent transcript accumulation. Chloroplast transcription run-on assays revealed that the transcription rate of PEP-dependent plastid genes was reduced in the STF-silenced leaves. Conversely, the exogenously added recombinant STF protein increased the transcription rate, suggesting a direct role of STF in plastid transcription. Etiolated seedlings of STF cosuppression lines showed defects in the light-triggered transition from etioplasts to chloroplasts, accompanied by reduced light-induced expression of plastid-encoded genes. * These results suggest that STF plays a critical role as an auxiliary factor of the PEP transcription complex in the regulation of plastid transcription and chloroplast biogenesis in higher plants. PMID- 22050605 TI - Prognostic significance of residual tumor in patients with epithelial ovarian carcinoma stage IV in a 20 year perspective. AB - OBJECTIVE: We aimed to evaluate prognostic factors impacting on overall survival during a 20 year period with substantial changes in surgical approach and chemotherapy management of patients with epithelial ovarian carcinoma stage IV. DESIGN: A retrospective population-based study. SETTING: The Norwegian Radium Hospital during 1985-2005. POPULATION: Three hundred and ninety-four patients with epithelial ovarian carcinoma stage IV treated at the Norwegian Radium Hospital. METHODS: The cohort was divided into two groups (1985-1995 and 1996 2005), and clinical and pathological characteristics were compared. Univariate and multivariate analyses were performed to identify prognostic factors during 1985-1995, 1996-2005 and 1985-2005. MAIN OUTCOME MEASURES: Prognostic factors and overall survival in the three periods. RESULTS: Median overall survival improved from 1985-1995 to 1996-2005 (from 1.3 to 2.1 years). More patients had macroscopic radical surgery (28 vs. 11%), received neoadjuvant chemotherapy and were treated with platinum-taxane combination therapy from 1996-2005 compared to 1985-1995. Patients with primary surgery had improved median overall survival from 1996-2005 compared to 1985-1995. In multivariate analyses, surgical approach was not a prognostic factor for overall survival, but chemotherapy was during 1985-2005. Postoperative residual tumor was a prognostic factor for overall survival in all periods. CONCLUSIONS: Macroscopic radical surgery is a strong prognostic factor for overall survival and is achievable in a subset of patients with epithelial ovarian carcinoma stage IV. Improved selection criteria for what treatment algorithm to choose for patients with epithelial ovarian carcinoma stage IV are warranted. PMID- 22050606 TI - alpha-Carbonic anhydrases are sulfatases with cyclic diol monosulfate esters. AB - Carbonic anhydrases (CA) catalyze activated ester hydrolysis in addition to the hydration of CO(2) to bicarbonate. They also show phosphatase activity with 4 nitrophenyl phosphate as substrate but not sulfatase with the corresponding sulfate. Here we prove that the enzyme is catalyzing the synthesis of cyclic diols from sulfate esters. 5-, 6- and 8-membered ring cyclic sulfates incorporating a neighboring secondary alcohol moiety were treated with CA II and yielded the corresponding cyclic diols. Inhibitory properties of obtained cyclic and original sulfate esters were then investigated on human carbonic anhydrase I (hCA I), hCA II, hCA IV and hCA VI (h = human isoform). K(I)-s of these compounds ranged between 32.7-423 MUM against hCA I, 2.13-32.4 MUM against hCA II, 13.7-234 MUM against hCA IV and 76-278 MUM against CA VI, respectively. The sulfatase activity of CA with such esters is amazing considering the fact that 4 nitrophenyl-sulfate is not a substrate of these enzymes. PMID- 22050607 TI - Adiponectin elevation by telmisartan ameliorates ischaemic myocardium in Zucker diabetic fatty rats with metabolic syndrome. AB - AIM: This study investigated whether telmisartan, a selective angiotensin type 1 (AT1) receptor antagonist and gamma peroxisome proliferator-activated receptor (PPAR-gamma) partial agonist, reduces myocardial ischaemia/reperfusion (I/R) injury in an experimental model of metabolic syndrome. METHODS: Zucker Diabetic Fatty (ZDF) rats were treated for 3 weeks with telmisartan at doses of 2, 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25-min occlusion of the left descending coronary artery followed by 2-h reperfusion (I/R). RESULTS: Telmisartan reduced the extension of the infarct size in a dose-dependent fashion and decreased the levels of plasma troponin I, a specific marker of myocardial damage. Telmisartan also caused a dose-dependent increase in adiponectin both in plasma and cardiac tissue of infarcted ZDF rats. These levels were minimally increased (p < 0.05 vs. vehicle) by telmisartan 7 mg/kg/day and reached the maximum values with the highest dose of 12 mg/kg/day (p < 0.01 vs. vehicle). In contrast, within the infarcted tissue telmisartan decreased the expression of markers of inflammation such as the transcription factor NF-kappaB, the toll-like receptors TLR2 and TLR4 as well as TNF-alpha cytokine. Nitrosative stress was maximal in vehicle-treated infarcted hearts as evidenced by increased expression of iNOS, which was almost abolished after treatement with telmisartan. CONCLUSIONS: Treatment of ZDF rats for 3 weeks with telmisartan, a dual angiotensin II receptor antagonist and partial PPAR-gamma receptor agonist, resulted in a significant reduction of myocardial damage induced by I/R and was associated with increased adiponectin and a decrease in inflammatory markers. PMID- 22050608 TI - Metagenomic analysis of a complex marine planktonic thaumarchaeal community from the Gulf of Maine. AB - Thaumarchaea, which represent as much as 20% of prokaryotic biomass in the open ocean, have been linked to environmentally relevant biogeochemical processes, such as ammonia oxidation (nitrification) and inorganic carbon fixation. We have used culture-independent methods to study this group because current cultivation limitations have proved a hindrance in studying these organisms. From a metagenomic data set obtained from surface waters from the Gulf of Maine, we have identified 36,111 sequence reads (containing 30 Mbp) likely derived from environmental planktonic Thaumarchaea. Metabolic analysis of the raw sequences and assemblies identified copies of the catalytic subunit required in aerobic ammonia oxidation. In addition, genes that comprise a nearly complete carbon assimilation pathway in the form of the 3-hyroxypropionate/4-hydroxybutyrate cycle were identified. Comparative genomics contrasting the putative environmental thaumarchaeal sequences and 'Candidatus Nitrosopumilus maritimus SCM1' revealed a number of genomic islands absent in the Gulf of Maine population. Analysis of these genomic islands revealed an integrase-associated island also found in distantly related microbial species, variations in the abundance of genes predicted to be important in thaumarchaeal respiratory chain, and the absence of a high-affinity phosphate uptake operon. Analysis of the underlying sequence diversity suggests the presence of at least two dominant environmental populations. Attempts to assemble complete environmental genomes were unsuccessful, but analysis of scaffolds revealed two diverging populations, including a thaumarchaeal-related scaffold with the full urease operon. Ultimately, the analysis revealed a number of insights into the metabolic potential of a predominantly uncultivated lineage of organisms. The predicted functions in the thaumarchaeal metagenomic sequences are directly supported by historic measurements of nutrient concentrations and provide new avenues of research in regards to understanding the role Thaumarchaea play in the environment. PMID- 22050609 TI - The attitudes of neonatal nurses towards extremely preterm infants. AB - AIM: The paper is a report of a study of the attitudes of neonatal nurses towards extremely preterm infants. BACKGROUND: Alongside advancing survival at extremely preterm gestational ages, ethical debates concerning the provision of invasive care have proliferated in light of the high morbidity. Despite nurses being the healthcare professionals who work closest with the infant and their family, their potential influence is usually ignored when determining how parents come to decisions about future care for their extremely premature infant. METHODS: A Q methodology was employed to explore the attitudes of neonatal nurses towards caring for extremely preterm infants. Data were collected between 2007 and 2008 and analysed using PQMethod and Card Content Analysis. RESULTS: Thirty-six nurses from six neonatal units in the United Kingdom participated. Although there was consensus around the professional role of the nurse, when faced with the complexities of neonatal nursing three distinguishing factors emerged: the importance of parental choice in decision-making, the belief that technology should be used to assess response to treatment, and the belief that healthcare professionals should undertake difficult decisions. CONCLUSION: Neonatal nurses report unexpected difficulties in upholding their professionally defined role through highly complex and ever varied decision-making processes. Recognition of individual attitudes to the care of extremely preterm infants and the role of the family in the face of difficult decisions should facilitate more open communication between the nurse and the parents and improve the experience of both the nurse and the family during these emotional situations. PMID- 22050610 TI - Randomized prospective trial on the occurrence of laparoscopic trocar site hernias. AB - INTRODUCTION: Laparoscopy has become the gold standard in an increasing number of procedures. We analyze the incidence of trocar site hernias (TSH) and determine whether closure of the external fascia prevents onset of TSH and possible complications. METHODS: We performed a simple-blind randomized trial with two groups, one in which all the orifices were closed by suturing the external fascia of the abdominal wall (group A), and another in which the orifices were left open, closing only the skin (group B). Monitoring for TSH lasted 2 years from the intervention. The trial has been registered at www.clinicaltrials.gov with the clinicaltrials.gov identifier number: NCT01240434. RESULTS: A total of 195 patients were randomized. Thirty-three were removed from the study after conversion to open surgery, early open reoperation, or loss to follow-up. The remaining 162 patients comprised the study population, 80 in group A and 82 in group B. We found no differences between the groups regarding basic demographic data, kind of surgery, or topographic distribution of the trocars. Five TSH were diagnosed-four in group A and one in group B (P=.176)-and there was no relation between TSH and trocar size (11 or 12 mm) or location. We found 10 wound infections, 7 in group A and 3 in group B (P=.154). CONCLUSION: Our study suggests that the onset of TSH does not depend on trocar size or location. There is no evidence that suture of the fascial defect prevents the onset of TSH. In addition, we found a trend toward a higher incidence of wound infection among patients in whom the fascia had been sutured. PMID- 22050613 TI - Ideas with impact. PMID- 22050612 TI - The role of cortical and hypothalamic histamine-3 receptors in the modulation of central histamine neurotransmission: an in vivo electrophysiology and microdialysis study. AB - The current study aimed to investigate the effect of histamine-3 (H(3)) receptors, expressed in the tuberomammillary nucleus (TMN) of the hypothalamus and in the prefrontal cortex (PFC), on histamine neurotransmission in the rat brain. The firing activity of histamine neurons in the TMN was measured using in vivo extracellular single-unit electrophysiology, under propofol anesthesia. Extracellular histamine levels were determined using the dual (PFC and TMN) probe microdialysis, in freely-moving animals. Histamine levels in dialysates were determined using high-performance liquid chromatography (HPLC) and fluorescence detection. It was found that systemic administration of the selective H(3) agonist, immepip, decreases, and the reverse H(3) /H(4)-agonist, thioperamide, increases the firing activity of histamine neurons in the TMN and the release of histamine in TMN and PFC. Local perfusion of immepip into the TMN increased, and thioperamide decreased, histamine levels in the TMN but not in the PFC. Local perfusion of immepip into the PFC, however, decreased extracellular histamine levels in both TMN and PFC. It can be concluded that brain H(3) receptors, and especially those expressed in the PFC, play an important role in the autoregulation of histamine neurotransmission. It is possible that H(3) receptors in the PFC are expressed on pyramidal neurons projecting to the TMN, and activation of these receptors diminishes glutamate excitatory input from PFC to the TMN. As the brain histamine system has a role in pathophysiology of psychotic, affective, cognitive, sleep and eating disorders, H(3) receptors are potential targets for future CNS medications. PMID- 22050614 TI - Challenges of patient-centred care: practice or rhetoric. PMID- 22050615 TI - Understanding medication safety in healthcare settings: a critical review of conceptual models. AB - Understanding medication safety in healthcare settings: a critical review of conceptual models Communication can impact on the way in which medications are managed across healthcare settings. Organisational cultures and the environmental context provide an added complexity to how communication occurs in practice. The aims of this paper are: to examine six models relating to medication safety in various hospital and community settings, to consider the strengths and limitations of each model and to explore their applications to medication safety practices. The models examined for their ability to address the complexity of the medication communication process include causal models, such as the Human Error Model and the System Analysis to Clinical Incidents Model, and exploratory models, such as the Shared Decision-Making Model, the Medication Decision-Making and Management Model, the Partnership Model and the Medication Communication Model. The Medication Communication Model provides particular insights into possible interactions between aspects that influence medication safety practices. The implications of all six models for healthcare practice and future research are also discussed. PMID- 22050616 TI - Deconstructing child and adolescent mental health: questioning the'taken-for granted'.... AB - Deconstructing child and adolescent mental health: questioning the 'taken-for granted'... We present a critical deconstructive reading, seeking to problematise 'taken-for-granted' assumptions in child and adolescent mental health (CAMH). The start point for this critical reading is conventional 'history-telling' within CAMH. The aim is not to take issue with the detail in such histories but to critically examine the texts, so as to highlight constructions that structure the presentation of conventional histories and possible purposes that such constructions may serve. The argument is that such conventional histories leave key questions not just unanswered, but unconsidered - a tendency that can be seen throughout the CAMH literature more generally. Therefore, we then pursue critical discussion of how 'taken-for-granted' constructions of CAMH enabled psychiatry to successfully expand its power and influence to establish hegemony over 'problem children'. We do not claim any closure to this critical reading; that is, we do not claim that our critical deconstructive reading is the only reading possible. Similarly, it is not presented in any sense as 'final word'. Rather our hope for this work is that it might stimulate readers to question the 'taken-for-granteds' that we present, and indeed others that they might identify themselves. In so doing, it is our hope that creative dialogue might ensue. PMID- 22050617 TI - Gender, sexuality and the participatory dimensions of a comparative life history policy study. AB - Gender, sexuality and the participatory dimensions of a comparative life history policy study In this paper, I explore how a critical feminist lens was a crucial element in creating a participatory policy study which used a qualitative design and comparative life history methodology. This study focused on Canadian nurses' political practice related to advocacy for lesbian health. Findings show that the combination of the gender lens and life history approach offers potential to create knowledge in ways aligned with health-promoting and emancipatory outcomes. However, the nature of participation and interaction by researcher and participants is contexualized and contested given complex dynamics of power that shape all aspects of this doctoral study process. The critical feminist lens with its focus on reflexivity informed the content and process of knowledge production in this study and shaped key turning points: the ways in which this policy study was conceptualized, the choice of comparative life history methodology, ethical considerations, data collection and analysis and representation of findings. Life history is unlikely to be the methodology that first comes to mind when undertaking a policy study. Its historical roots are associated with biographical, oral history and narrative approaches, which typically aim to elicit understanding of lived experience. Yet, it was this very aspect, this focus on lived experience, which rendered life history methodology fitting as I contemplated how to examine the relationship between nurses and policy. I was interested in understanding nurses' political practice, how policy influenced nurses' capacity to advocate in their everyday lives, as well as nurses' impacts on policy processes and their larger social worlds. PMID- 22050618 TI - A discursive exploration of the practices that shape and discipline nurses' responses to postoperative delirium. AB - A discursive exploration of the practices that shape and discipline nurses' responses to postoperative delirium Although delirium is classified as a medical emergency, it is often not treated as such by health care providers. The aim of this study was to critically examine, through a poststructural, Foucauldian concept of discourse, the language practices and discourses that shape and discipline nurses' care of older adults with postoperative delirium (POD) with a purpose to question accepted nursing practice. The study was based on data collected from face-to-face, in-depth, personal interviews with six nurses who work on an acute postoperative patient care unit. Five analytic readings of the data identified two prominent discourses at work in nursing practice which influenced the care of patients with POD. These were identified as discourses of legitimacy/illegitimacy and discourses of nursing work. Through the process of poststructural analysis it became evident that one overriding discourse - the biomedical/scientific discourse - served to direct, legitimize and govern all other discourses. The findings of this study have implications for nursing knowledge and practice, length of hospital stay and improved patient outcomes. This study builds on previous work and is the first study to conduct a discourse analysis illuminating nurses' responses to POD through comparison with other acute medical emergencies from a poststructural perspective. PMID- 22050619 TI - Living with an adult family member using advanced medical technology at home. AB - Living with an adult family member using advanced medical technology at home An increased number of chronically ill adults perform self-care while using different sorts of advanced medical technology at home. This hermeneutical study aimed to gain a deeper understanding of the meaning of living with an adult family member using advanced medical technology at home. Eleven next of kin to adults performing self-care at home, either using long-term oxygen from a cylinder or ventilator, or performing peritoneal or haemodialysis, were interviewed. The qualitative interviews were analysed using a Gadamerian methodology. The main interpretation explained the meaning as rhythmical patterns of connectedness versus separation, and of sorrow versus reconciliation. Dependence on others was shown in the need for support from healthcare professionals and significant others. In conclusion, next of kin took considerable responsibility for dependent-care. All next of kin were positive to the idea of bringing the technology home, even though their own needs receded into the background, while focusing on the best for the patient. The results were discussed in relation to dependent-care and transition, which may have an influence on the self-care of next of kin and patients. The study revealed a need for further nursing attention to next of kin in this context. PMID- 22050620 TI - Morbidly obese patients and lifestyle change: constructing ethical selves. AB - Morbidly obese patients and lifestyle change: constructing ethical selves In contemporary societies, bodily size is an important part of individuals' self representation. As the number of persons clinically diagnosed as morbidly obese increases, programmes are developed to make people reduce weight by changing their lifestyle, and for some, by bariatric surgery. This article presents findings from interviews with 12 participants undergoing a prerequisite course prior to bariatric surgery that is intended both as a preparation for further (surgical) treatment and as a tool to empower individuals regarding lifestyle changes. In this study, we investigate how power operates by looking at how the participants position themselves throughout the course. Findings reveal how participants construct their ability to act in line with norms of lifestyle change. They do this by positioning themselves as both included group members and as 'morally' acceptable individuals. Despite some resistance, the participants tend to glide into the role of 'good patients' acting in compliance with the aims of the course in their hope and striving for new positions as 'normal-sized'. The intention in the course is to empower individuals towards lifestyle changes. The findings provide a basis to question whether these kinds of courses create new forms of compliance and dependency. PMID- 22050621 TI - Promoting the health of Europeans in a rapidly changing world: a historical study of the implementation of World Health Organisation policies by the Nursing and Midwifery Unit, European Regional Office, 1970-2003. AB - Promoting the health of Europeans in a rapidly changing world: a historical study of the implementation of World Health Organisation policies by the Nursing and Midwifery Unit, European Regional Office, 1970-2003 The World Health Organisation (WHO) was inaugurated in 1948. Formed in a period of post-war devastation, WHO aimed to develop and meet goals that would rebuild the health of shattered populations. The historical study reported here examined the work of the Nursing and Midwifery Unit (NMU) of WHO's European Regional Office during the later part of the twentieth century. The study examined archive sources lodged at the NMU archive. The sources included manuscripts relating to important NMU initiatives, reports and papers published by WHO, and a range of secondary sources. The study identified three main driving forces in the work of the NMU of the European Regional Office of WHO. One of the strongest of these was a drive to develop and promote the nursing profession within the countries of the European Region. The second was the promulgation and implementation of the positive public health strategies of WHO, particularly its '38 Targets for Health for All by the Year 2000'. The third focussed on securing equity across the European continent and on promoting the development of the nursing professions in poorer and less-developed countries. The study concludes that the nursing professions in European states grew in strength and influence, and that the health of populations improved throughout the continent between 1970 and 2003. It discusses the extent to which the role of the NMU in these advances may have been significant. PMID- 22050622 TI - Quantifying the relationships of blood pressure with weight, height and body mass index in Chinese children and adolescents. AB - AIM: The aim of this study was to quantify the relationships of height, weight and body mass index (BMI) with blood pressure (BP) levels in Chinese children and adolescents. METHODS: Height, weight, BMI and BP measurements were obtained from a nationally representative sample of 231,227 children aged 7-18 years. Body size measurements were converted to age- and sex-specific standard deviation (SD) scores. The relationships between body size and BP measurements were assessed using linear regression analysis. RESULTS: All body size measurements were significantly associated with BP levels. Systolic BP increased 4.14, 3.70 and 2.88 mmHg in boys and 2.98, 2.63 and 1.87 mmHg in girls, corresponding to 1 SD increase in weight, BMI and height, respectively. A similar pattern was also observed for diastolic BP. After adjustment for height, systolic BP increased substantially with increasing weight (3.96 mmHg/SD increase for boys and 2.92 mmHg for girls). With adjustment for weight, systolic BP increased slightly with 1 SD increase in height (0.27 mmHg for boys and 0.10 mmHg for girls). The strength of the association between a body size measurement and BP varied among different ages, peaked at 10-11 years in girls and around 12-14 years in boys. CONCLUSIONS: Weight is the most powerful driving force of BP in children and adolescents, followed by BMI and height. Height has little impact on BP in children with a given weight, while weight has considerable impact on BP in children with a given height. PMID- 22050623 TI - A preliminary study of changes in tear film proteins in the feline eye following nictitating membrane removal. AB - OBJECTIVE: To investigate the influence of nictitating membrane (third eyelid) removal on selected proteins in feline tears. ANIMAL STUDIED: Domestic short haired cats (7-17 months; 2.6-5.2 kg) were used. PROCEDURES: Eye-flush tears were collected periodically for up to 18 weeks from both eyes of animals with nictitating membranes removed, but nictitating gland left intact, (n = 4) or with nictitating membranes intact (n = 4). Tear comparisons were based on total protein content (TPC) using micro bicinchoninic acid assay, immunoglobulin A (IgA), and matrix-metalloproteinase (MMP)-9 measurements using sandwich enzyme linked immunosorbent assay (ELISA) and tear gelatinase activity using gelatin zymography. Expression of MMP-2 and -9 in nictitating membranes removed at baseline (week 0) and eyes collected at 18 weeks were also investigated in histological sections using immunoperoxidase for visualization. RESULTS: Nictitating membrane removal did not significantly change TPC and MMP-9 in tears within the first 4 weeks. MMP-9 was not detected by ELISA in tears from eyes without nictitating membranes from week 5 onwards. IgA (%IgA of TPC) data varied between animals. Gelatin zymography showed increased MMP-2 and -9 activity in tears from eyes without nictitating membranes at week 1 and a decrease following week 2 post-surgery. MMP-2 and -9 were immunolocalised to conjunctival goblet cells of removed nictitating membranes and to the conjunctival epithelium, respectively. After 18 weeks, the distribution of MMPs in tissue was comparable between eyes with and without nictitating membranes. CONCLUSIONS: Based on this preliminary study, nictitating membrane removal appeared to cause long-term changes in expression of tear proteins, including reduced MMP-9 expression. PMID- 22050624 TI - Comparison of intraocular pressure measurements between the Tono-Pen XL(r) and Perkins(r) applanation tonometers in dogs and cats. AB - OBJECTIVE: To compare the accuracy between two applanation tonometers, Tono-Pen XL((r)) and Perkins((r)), in ophthalmoscopically normal dogs and cats. ANIMALS: Both eyes of 25 conscious and healthy dogs and cats were evaluated. Both eyes of five dogs and cats immediately after sacrifice were used as controls for the postmortem study. PROCEDURE: In conscious animals, the tonometry was performed with topical anesthesia using 0.5% proxymetacaine eye drops for both tonometers and 1% fluorescein eye drops for the Perkins tonometer. Readings of intraocular pressure (IOP) in the postmortem study were taken using manometry and tonometry by Tono-Pen XL((r)) and Perkins((r)). RESULTS: The correlation coefficient (r(2) ) in dogs between manometry and applanation tonometers Tono-Pen XL((r)) and Perkins((r)) were, respectively, 0.896 and 0.981 and in cats were 0.905 and 0.988. The mean IOP values in conscious dogs with Tono-Pen XL((r)) and Perkins((r)) were, respectively, 17.5 +/- 3.7 mmHg (10.0-25.0 mmHg) and 15.3 +/- 2.1 mmHg (12.0-19.8 mmHg) and in conscious cats were 16.8 +/- 3.6 mmHg (10.5-24.5 mmHg) and 15.5 +/- 1.3 mmHg (13.0-18.5 mmHg). CONCLUSION: There was a strong correlation between the IOP values obtained by direct ocular manometry and the Tono-Pen XL((r)) and Perkins((r)) tonometers in dogs and cats. There was no statistically significant difference between the mean IOP obtained with both tonometers in conscious animals, there was, however, a difference between the minimum and mainly in the maximum values that were on average 5-6 mmHg higher with Tono-Pen XL((r)) than those measured with Perkins((r)), which justifies a table of normal values differentiated for each tonometer. PMID- 22050625 TI - Cardiomyocytes generated from CPVTD307H patients are arrhythmogenic in response to beta-adrenergic stimulation. AB - Sudden cardiac death caused by ventricular arrhythmias is a disastrous event, especially when it occurs in young individuals. Among the five major arrhythmogenic disorders occurring in the absence of a structural heart disease is catecholaminergic polymorphic ventricular tachycardia (CPVT), which is a highly lethal form of inherited arrhythmias. Our study focuses on the autosomal recessive form of the disease caused by the missense mutation D307H in the cardiac calsequestrin gene, CASQ2. Because CASQ2 is a key player in excitation contraction coupling, the derangements in intracellular Ca(2+) handling may cause delayed afterdepolarizations (DADs), which constitute the mechanism underlying CPVT. To investigate catecholamine-induced arrhythmias in the CASQ2 mutated cells, we generated for the first time CPVT-derived induced pluripotent stem cells (iPSCs) by reprogramming fibroblasts from skin biopsies of two patients, and demonstrated that the iPSCs carry the CASQ2 mutation. Next, iPSCs were differentiated to cardiomyocytes (iPSCs-CMs), which expressed the mutant CASQ2 protein. The major findings were that the beta-adrenergic agonist isoproterenol caused in CPVT iPSCs-CMs (but not in the control cardiomyocytes) DADs, oscillatory arrhythmic prepotentials, after-contractions and diastolic [Ca(2+) ](i) rise. Electron microscopy analysis revealed that compared with control iPSCs-CMs, CPVT iPSCs-CMs displayed a more immature phenotype with less organized myofibrils, enlarged sarcoplasmic reticulum cisternae and reduced number of caveolae. In summary, our results demonstrate that the patient-specific mutated cardiomyocytes can be used to study the electrophysiological mechanisms underlying CPVT. PMID- 22050626 TI - The influence of sex, age and BMI on the degeneration of the lumbar spine. AB - Previous research on lumbar spine osteophyte formation has focused on patterned development and the relation of age and sex to degeneration within the vertebral bodies. The inclusion of osteophytes originating on the laminae and body mass index (BMI) may result in a more complete evaluation. This study investigates lumbar osteophyte development on the laminae and vertebral bodies to determine whether osteophyte development: (i) is related bilaterally, at different lumbar levels, and superior and inferior margins; (ii) on the laminae and vertebral bodies are reciprocally dependent responses; (iii) is correlated with sex, age and/or BMI. Seventy-six individuals (39 females, 37 males) were randomly selected from a modern skeletal collection (Bass Donated Collection). Osteophyte development was scored in eight regions on each vertebra at all five lumbar levels. A factor analysis considered all 40 scoring regions and Pearson's correlation analyses assessed the relatedness of age and BMI with the consequent factors. The factor analysis separated the variables into two similar factors for males and females defined as: (i) superior and inferior vertebral body scores and (ii) superior laminar scores at higher lumbar levels. The factor analysis also determined a third factor for females defined as: (iii) inferior laminar scores at lower lumbar levels. The severity of vertebral body osteophytes increased with age for both sexes. Additionally for females, as BMI increased, osteophyte severity increased for both the superior laminar margins higher in the column and the vertebral bodies. Dissimilarities between the factors in males and females and the correlation of BMI to osteophyte severity exclusively in females provide evidence for different biomechanical processes influencing osteophyte development. PMID- 22050628 TI - Boron accumulation and toxicity in hybrid poplar (Populus nigra * euramericana). AB - Poplars accumulate high B concentrations and are thus used for the phytomanagement of B contaminated soils. Here, we performed pot experiments in which Populus nigra * euramericana were grown on a substrate with B concentrations ranging from 13 to 280 mg kg(-1) as H(3)BO(3). Salix viminalis, Brassica juncea, and Lupinus albus were grown under some growing conditions for comparison. Poplar growth was unaffected at soil B treatment levels up to 93 mg kg(-1). Growth was progressively reduced at levels of 168 and 280 mg kg(-1). None of the other species survived at these substrate B levels. At leaf B concentrations <900 mg kg(-1) only <10% of the poplar leaf area showed signs of toxicity. Neutron radiography revealed that chlorotic leaf tissues had B concentrations of 1000-2000 mg kg(-1), while necrotic tissues had >2000 mg kg( 1). Average B concentrations of up to 3500 mg kg(-1) were found in leaves, while spots within leaves had concentrations >7000 mg kg(-1), showing that B accumulation in leaf tissue continued even after the onset of necrosis. The B accumulation ability of P. nigra * euramericana is associated with B hypertolerance in the living tissue and storage of B in dead leaf tissue. PMID- 22050627 TI - Melatonin synergistically enhances cisplatin-induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK-OV-3 cells. AB - To evaluate melatonin's ability to enhance ovarian cancer cells to cisplatin treatment for ovarian cancer, this study was performed. Melatonin by itself had no significant cytotoxicity against SK-OV-3 cells, while cisplatin suppressed the cell viability in a dose-dependent manner. Combined treatment with cisplatin and melatonin synergistically inhibited the viability of SK-OV-3 cells with the synergism between two drugs (1 > combination index). In contrast, melatonin revealed the protective effect against cisplatin-induced cytotoxicity in OSEN normal ovarian epithelial cells. Cotreatment with cisplatin and melatonin increased the sub-G1 DNA contents and TdT-mediated dUTP nick end-labeling (TUNEL) positive cells compared with cisplatin control in SK-OV-3 cells, suggesting that melatonin augments cisplatin-induced apoptosis. Consistently, combined treatment of cisplatin and melatonin increased the cleavage of caspase-3 and poly-(ADP ribose) polymerase (PARP). Importantly, melatonin synergistically inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) along with dephosphorylation of 90-kDa ribosomal S6 kinase (p90RSK) and heat shock protein 27 (HSP27) induced by cisplatin. Furthermore, melatonin remarkably blocked the expression and colocalization of p90RSK and HSP27 by combination treatment with cisplatin. Taken together, our findings demonstrate that melatonin enhances cisplatin-induced apoptosis via the inactivation of ERK/p90RSK/HSP27 cascade in SK-OV-3 cells as a potent synergist to cisplatin treatment. PMID- 22050629 TI - Increased risk of recurrence of membranous nephropathy after related donor kidney transplantation. PMID- 22050630 TI - Identification of exonic regions in DNA sequences using cross-correlation and noise suppression by discrete wavelet transform. AB - BACKGROUND: The identification of protein coding regions (exons) in DNA sequences using signal processing techniques is an important component of bioinformatics and biological signal processing. In this paper, a new method is presented for the identification of exonic regions in DNA sequences. This method is based on the cross-correlation technique that can identify periodic regions in DNA sequences. RESULTS: The method reduces the dependency of window length on identification accuracy. The proposed algorithm is applied to different eukaryotic datasets and the output results are compared with those of other established methods. The proposed method increased the accuracy of exon detection by 4% to 41% relative to the most common digital signal processing methods for exon prediction. CONCLUSIONS: We demonstrated that periodic signals can be estimated using cross-correlation. In addition, discrete wavelet transform (DWT) can minimise noise while maintaining the signal. The proposed algorithm, which combines cross-correlation and DWT, significantly increases the accuracy of exonic region identification. PMID- 22050631 TI - Treatment of chronic heel osteomyelitis in vasculopathic patients. Can the combined use of Integra(r) , skin graft and negative pressure wound therapy be considered a valid therapeutic approach after partial tangential calcanectomy? AB - Osteomyelitis of the calcaneus is a difficult problem to manage. Patients affected by osteomyelitis of the calcaneus often have a below-the-knee amputation because of their comorbidity. In this article, we present seven cases of heel ulcerations with chronic osteomyelitis treated with Integra((r)) Dermal Regeneration Template, skin graft and negative pressure wound therapy after partial tangential calcanectomy, discussing the surgical and functional results. In this casuistic of patients, all wounds healed after skin grating of the neodermis generated by Integra((r)), with no patient requiring a below-knee amputation. PMID- 22050632 TI - Use of laparoscopic sleeve gastrectomy and adjustable gastric banding for suboptimally controlled diabetes in Hong Kong. AB - Bariatric surgery has recently been considered as an option for treatment of type 2 diabetes mellitus (T2DM). We assessed the effect of laparoscopic gastric banding and laparoscopic sleeve gastrectomy in a cohort of 39 T2DM Chinese patients with body mass index (BMI) over 30 kg/m(2) . Their mean body weights and BMI before surgery were 108 kg and 40 kg/m(2) , respectively, and 18 patients (46%) had suboptimal diabetic control (HbA1c >7%). After a mean follow-up of 27 months, 4 of 11 insulin-dependent patients (36%) were able to stop their insulin therapy, and 18 patients (46%) achieved remission of T2DM (HbA1c <6.5% without the use of medication). Glycaemic control remained poor in only nine other patients (27%). Logistic regression analysis showed that a short history of T2DM and high BMI could predict remission of diabetes after restrictive procedures. Our results suggest that restrictive surgery can significantly improve glycaemic control in obese T2DM patients. PMID- 22050634 TI - Environmental factors determining ammonia-oxidizing organism distribution and diversity in marine environments. AB - Ammonia-oxidizing bacteria (AOB) and archaea (AOA) play a vital role in bridging the input of fixed nitrogen, through N-fixation and remineralization, to its loss by denitrification and anammox. Yet the major environmental factors determining AOB and AOA population dynamics are little understood, despite both groups having a wide environmental distribution. This study examined the relative abundance of both groups of ammonia-oxidizing organisms (AOO) and the diversity of AOA across large-scale gradients in temperature, salinity and substrate concentration and dissolved oxygen. The relative abundance of AOB and AOA varied across environments, with AOB dominating in the freshwater region of the Chesapeake Bay and AOA more abundant in the water column of the coastal and open ocean. The highest abundance of the AOA amoA gene was recorded in the oxygen minimum zones (OMZs) of the Eastern Tropical South Pacific (ETSP) and the Arabian Sea (AS). The ratio of AOA : AOB varied from 0.7 in the Chesapeake Bay to 1600 in the Sargasso Sea. Relative abundance of both groups strongly correlated with ammonium concentrations. AOA diversity, as determined by phylogenetic analysis of clone library sequences and archetype analysis from a functional gene DNA microarray, detected broad phylogenetic differences across the study sites. However, phylogenetic diversity within physicochemically congruent stations was more similar than would be expected by chance. This suggests that the prevailing geochemistry, rather than localized dispersal, is the major driving factor determining OTU distribution. PMID- 22050635 TI - TOP3A, a new partner gene fused to MLL in an adult patient with de novo acute myeloid leukaemia. PMID- 22050636 TI - Detection and functional characterization of a large genomic deletion resulting in decreased pathogenicity in Ralstonia solanacearum race 3 biovar 2 strains. AB - Bacterial wilt (brown rot) disease of potato caused by Ralstonia solanacearum is one of the most important bacterial diseases and a major constraint on potato production worldwide. Through a comparative genomic analysis between R. solanacearum'race 3 biovar 2' (R3bv2) strains, we identified a 77 kb region in strain UW551 which is specifically absent in the hypoaggressive strain IPO1609. We proved that IPO1609 indeed carries a 77 kb genomic deletion and provide genetic evidence that occurrence of this deletion is responsible for almost complete loss of pathogenicity of this strain. We carried out a functional analysis of this 77 kb region in strain UW551 using a combination of gene deletion and functional complementation approaches which identified the methionine biosynthesis genes metER as having a major contribution to IPO1609 pathogenesis. Deletion of the metER genes significantly impacts pathogenicity of R3bv2 strains but does not lead to methionine auxotrophy nor reduced ability to multiply in planta. In addition, this study indicated that three type III secretion system effectors or a type VI secretion system present within the 77 kb region have no or very minor contribution to pathogenicity. PMID- 22050637 TI - The sulfated polysaccharide fucoidan stimulates osteogenic differentiation of human adipose-derived stem cells. AB - Human adipose-derived stem cells (hADSCs) are an attractive source for cell therapies, because they can be obtained from aspirated adipose tissues with the capacity of proliferation and differentiation into several mesenchymal lineages under certain conditions. Sulfated polysaccharides, including heparin, modulate osteogenic differentiation of stem cells through the regulation of growth factor binding and signaling pathways. Here, we examined the effects of the sulfated polysaccharide fucoidan on osteogenic differentiation of hADSCs. Strikingly, fucoidan treatment resulted in increased alkaline phosphatase (ALP) activity and alizarin red and von Kossa staining. At the molecular level, fucoidan treatment enhanced the expression of osteogenesis-specific marker genes, including ALP, osteopontin, type I collagen, Runt-related transcription factor 2, and osteocalcin. Furthermore, fucoidan also promoted the osteogenic differentiation of another mesenchymal cell lineage, human amniotic fluid stem cells. These findings strongly suggest that fucoidan enhances osteogenic differentiation of hADSCs and possibly other mesenchymal cell lineages, indicating that it may be a potential candidate for promoting bone regeneration. PMID- 22050638 TI - Decrease in thyroid adenoma associated (THADA) expression is a marker of dedifferentiation of thyroid tissue. AB - BACKGROUND: Thyroid adenoma associated (THADA) has been identified as the target gene affected by chromosome 2p21 translocations in thyroid adenomas, but the role of THADA in the thyroid is still elusive. The aim of this study was to quantify THADA gene expression in normal tissues and in thyroid hyper- and neoplasias, using real-time PCR. METHODS: For the analysis THADA and 18S rRNA gene expression assays were performed on 34 normal tissue samples, including thyroid, salivary gland, heart, endometrium, myometrium, lung, blood, and adipose tissue as well as on 85 thyroid hyper- and neoplasias, including three adenomas with a 2p21 translocation. In addition, NIS (sodium-iodide symporter) gene expression was measured on 34 of the pathological thyroid samples. RESULTS: Results illustrated that THADA expression in normal thyroid tissue was significantly higher (p < 0.0001, exact Wilcoxon test) than in the other tissues. Significant differences were also found between non-malignant pathological thyroid samples (goiters and adenomas) and malignant tumors (p < 0.001, Wilcoxon test, t approximation), anaplastic carcinomas (ATCs) and all other samples and also between ATCs and all other malignant tumors (p < 0.05, Wilcoxon test, t approximation). Furthermore, in thyroid tumors THADA mRNA expression was found to be inversely correlated with HMGA2 mRNA. HMGA2 expression was recently identified as a marker revealing malignant transformation of thyroid follicular tumors. A correlation between THADA and NIS has also been found in thyroid normal tissue and malignant tumors. CONCLUSIONS: The results suggest THADA being a marker of dedifferentiation of thyroid tissue. PMID- 22050639 TI - The next generation of psychological autopsy studies. Part I. Interview content. AB - The psychological autopsy (PA) is a systematic method to understand the psychological and contextual circumstances preceding suicide. The method requires interviews with one or more proxy respondents (i.e., informants) of decedents. The methodological challenges that need to be addressed when determining the content of these research interviews for PA studies are described and recommendations are made for meeting these challenges in future PA investigations. Ways to improve the data collected about mental disorders and life events--domains that are assessed in almost all PA studies--are discussed at length. Other understudied content areas considered include the role of personality traits, medical illness and functional limitations, availability of lethal agents, medications, and select distal variables including child maltreatment and family history of mental disorders and suicide. The benefits and challenges to using common protocols across studies are also discussed. PMID- 22050640 TI - Measurements of genomic GC content in plant genomes with flow cytometry: a test for reliability. AB - * Knowledge of the phylogenetic pattern and biological relevance of the base composition of large eukaryotic genomes (including those of plants) is poor. With the use of flow cytometry (FCM), the amount of available data on the guanine + cytosine (GC) content of plants has nearly doubled in the last decade. However, skepticism exists concerning the reliability of the method because of uncertainty in some input parameters. * Here, we tested the reliability of FCM for estimating GC content by comparison with the biochemical method of DNA temperature melting analysis (TMA). We conducted measurements in 14 plant species with a maximum currently known GC content range (33.6-47.5% as measured by FCM). We also compared the estimations of the GC content by FCM with genomic sequences in 11 Oryza species. * FCM and TMA data exhibited a high degree of correspondence which remained stable over the relatively wide range of binding lengths (3.39-4.09) assumed for the base-specific dye used. A high correlation was also observed between FCM results and the sequence data in Oryza, although the latter GC contents were consistently lower. * Reliable estimates of the genomic base composition in plants by FCM are comparable with estimates obtained using other methods, and so wider application of FCM in future plant genomic research, although it would pose a challenge, would be supported by these findings. PMID- 22050641 TI - The validity of the Canadian Triage and Acuity Scale in predicting resource utilization and the need for immediate life-saving interventions in elderly emergency department patients. AB - BACKGROUND: We evaluated the validity of the Canadian Triage and Acuity Scale (CTAS) in elderly emergency department (ED) patients. In particular, we examined the sensitivity and specificity of the CTAS for identifying elderly patients who received an immediate life-saving intervention in the ED. METHODS: We reviewed the medical records of consecutive patients who were 65 years of age or older and presented to a single academic ED within a three-month period. The CTAS triage scores were compared to actual patient course, including disposition, discharge outcome and resource utilization. We calculated the sensitivity and specificity of the CTAS triage for identifying patients who received an immediate intervention. RESULTS: Of the 1903 consecutive patients who were >= 65 years of age, 113 (5.9%) had a CTAS level of 1, 174 (9.1%) had a CTAS level of 2, 1154 (60.6%) had a CTAS level of 3, 347 (18.2%) had a CTAS level of 4, and 115 (6.0%) had a CTAS level of 5. As a patient's triage score increased, the severity (such as mortality and intensive care unit admission) and resource utilization increased significantly. Ninety-four of the patients received a life-saving intervention within an hour following their arrival to the ED. The CTAS scores for these patients were 1, 2 and 3 for 46, 46 and 2 patients, respectively. The sensitivity and specificity of a CTAS score of <= 2 for identifying patients for receiving an immediate intervention were 97.9% and 89.2%, respectively. CONCLUSIONS: The CTAS is a triage tool with high validity for elderly patients, and it is an especially useful tool for categorizing severity and for recognizing elderly patients who require immediate life-saving intervention. PMID- 22050642 TI - Aqueous humor vascular endothelial growth factor in dogs: association with intraocular disease and the development of pre-iridal fibrovascular membrane. AB - OBJECTIVE: To examine the concentrations of vascular endothelial growth factor (VEGF) in aqueous humor of dogs with intraocular disease and to evaluate the association of aqueous humor VEGF with pre-iridal fibrovascular membrane (PIFM) formation. PROCEDURES: Two hundred and twenty six aqueous humor samples and 101 plasma samples were collected from 178 dogs with a variety of intraocular diseases (including cataract, primary glaucoma, uveitic glaucoma, aphakic/pseudophakic glaucoma, retinal detachment, lens luxation, and intraocular neoplasia), and aqueous humor was collected from 13 ophthalmically normal control dogs. Systemic disease status and administration of select medications were recorded. Aqueous and plasma VEGF was assayed via enzyme-linked immunosorbant assay validated for canine VEGF. Available histopathology samples were examined for the presence of PIFM. Where present, PIFMs were categorized as none, cellular, vascular or fibrous, and fibrovascular. Data were evaluated by mixed model anova, with application of Tukey-Kramer adjustment for multiple comparisons. RESULTS: There was no association between aqueous humor and plasma VEGF levels. Compared with normal controls, aqueous humor VEGF was significantly elevated for all intraocular diseases (P < 0.05) except for primary and diabetic cataracts. Systemic disease and administered medications had no significant effect on aqueous humor VEGF concentration. Compared to dogs without PIFM, aqueous humor VEGF was significantly higher in dogs with fibrovascular PIFM (P = 0.001), but not cellular (P = 0.1704) or fibrous/vascular PIFM (P = 0.0667). CONCLUSIONS: These findings confirm that VEGF is commonly elevated in aqueous humor of dogs with intraocular disease and likely plays a role in the causation or progression of a variety of intraocular disorders, including the development of PIFM. PMID- 22050643 TI - Medical assessment for child sexual abuse: a post-code lottery? AB - AIM: To describe the number of children and young people in New Zealand who receive a medical assessment for sexual abuse, the proportion of those where there is concern about sexual abuse who receive such assessments and the way in which assessment services are structured. METHODS: Medical assessments for child and adolescent sexual abuse over 12 months were counted by direct communication with health providers throughout New Zealand, and compared with the number of cases substantiated by statutory child protective services, the number of claims for counselling for mental injury from sexual abuse and the regional population. All doctors providing medical assessments were surveyed as to how this was organised by region. RESULTS: There were 804 medical assessments. Child protective services regarded 1207 cases as substantiated, and 1434 claims for mental injury were lodged. There was marked regional variation. In a matched sample, only 38% of cases of substantiated sexual abuse were seen for a medical assessment. A doctor with expertise in the assessment of sexual abuse was available in most areas, but service structure varied widely. The availability of nurse or social work support was poor. The proportion of children and adolescents receiving a medical assessment, and the quality of service structure, was directly related to regional population. CONCLUSIONS: Health assessments for alleged child and adolescent sexual abuse are relatively infrequent, nationally inconsistent and often poorly supported by local health systems. There is also marked but apparently unrelated regional variation in statutory child protection practice. PMID- 22050644 TI - Gender differences in iridocorneal angle morphology: a potential explanation for the female predisposition to primary angle closure glaucoma in dogs. AB - OBJECTIVE: Female dogs have approximately twice the risk of males for developing primary angle closure glaucoma (PACG). The cause of this gender difference is unknown, but one theory proposes that the gender differences in iridocorneal angle morphology are involved in this risk differential. PROCEDURES: Fifty beagles (25 males, 25 females) were included into this study and had normal baseline ophthalmic examinations. Normal dogs were selected so as to avoid any potentially confounding influence of goniodysgenesis. Standardized 20-MHz high resolution ultrasound images of the iridocorneal angle were acquired from one eye of each dog with the scan plane perpendicular to the limbus in the superior temporal quadrant. Images were imported into ImageJ, and the angle opening distance (AOD) and angle recess area (ARA) were measured by a masked observer, and the analysis of variance method was used to compare differences. RESULTS: The mean (+/-SD) AOD was significantly smaller for female dogs (0.847 +/- 0.241 mm) vs. male dogs (1.058 +/- 0.322 mm) P-value = 0.012. The mean (+/- SD) ARA tended to be smaller for female dogs (0.584 +/- 0.278 mm) vs. male dogs (0.748 +/- 0.385 mm), but this difference was not significant (P-value = 0.092). CONCLUSIONS: Female dogs have a significantly smaller AOD vs. males. This difference may render the female iridocorneal angle more susceptible to closure and may partially explain the 2:1 female/male predisposition to PACG. Further studies using goniodysgenic dogs are warranted. PMID- 22050645 TI - Epidemiology and clinical characteristics of hospitalized patients with pandemic influenza A (H1N1) 2009 infections: the effects of bacterial coinfection. AB - BACKGROUND: Numerous reports have described the epidemiological and clinical characteristics of influenza A (H1N1) 2009 infected patients. However, data on the effects of bacterial coinfection on these patients are very scarce. Therefore, this study explores the impact of bacterial coinfection on the clinical and laboratory parameters amongst H1N1 hospitalized patients. FINDINGS: This retrospective study involved hospitalized patients with laboratory-confirmed H1N1 infections (September 2009 to May 2010). Relevant clinical data and the detection of bacterial coinfection from respiratory or sterile site samples were obtained. Multiplex PCR was used to determine the co-existence of other respiratory viruses. Comparison was made between patients with and without bacterial coinfection. The occurrence of coinfection was 34%; 14 (28%) bacterial and only 3 (6%) viral. Mycoplasma pneumoniae (n = 5) was the commonest bacteria followed by Staphylococcus aureus (n = 3). In univariate analysis, clinical factors associated with bacterial coinfection were age > 50 years (p = 0.02), presence of comorbidity (p = 0.04), liver impairment (p = 0.02), development of complications (p = 0.004) and supplemental oxygen requirement (p = 0.02). Leukocytosis (p = 0.02) and neutrophilia (p = 0.004) were higher in bacterial coinfected patients. Multivariate logistic regression analysis revealed that age > 50 years and combined complications were predictive of bacterial coinfection. CONCLUSIONS: Bacterial coinfection is not uncommon in H1N1 infected patients and is more frequently noted in the older aged patients and is associated with higher rates of complications. Also, as adjunct to clinical findings, clinicians need to have a higher index of suspicion if neutrophilia was identified at admission as it may denote bacterial coinfection. PMID- 22050646 TI - Trust and trustworthiness in nursing: an argument-based literature review. AB - Caring requires nurses to establish trusting relationships with patients and to be trustworthy professionals. This article provides insight into the conceptual understanding of trust and trustworthiness in nursing through an argument-based literature review of 17 articles published between 1980 and 2010. Trust is characterized as an attitude relying with confidence on someone. The importance of trust relationships is considered by addressing the imbalances of power in nurse-patient relationships as they increase the vulnerability and dependency of the truster. Trust is considered as a process, and time, reliance on others, risk and fragility are identified as basic attributes of trust. However, trustworthiness is inadequately explored in the nursing ethics literature. Nurse educators have a responsibility to ensure that nurses are equipped with the attitudes and knowledge that are needed to establish trusting nurse-patient relationships. PMID- 22050647 TI - Repetitive transplantation of different cell types sequentially improves heart function after infarction. AB - Cell-based therapy is considered a novel and potentially new strategy in regenerative medicine. But the efficacy of cell-based therapy has been limited by the poor survival of the transplanted cells in an ischaemic environment. The goal of the present study is to present a possibility to increase survival of the transplanted cardiomyocytes, by increasing the vascularization of the infarcted area. First, we injected endothelial progenitor cells (EPCs) to augment the vascular density in infarcted areas and to improve the benefit of a subsequent Tx of foetal cardiomyocytes. Serial echocardiography indeed showed significant improvement of the left ventricular function after application of EPC and a significant additive improvement after Tx of foetal cardiomyocytes. In contrast, repetitive EPC transplantation as a control group did not show an additional improvement after the second transplantation. Histologically, cells could be readily detected after Tx by BrdU-staining for EPC and by carboxy-fluorescein diacetate succinimidyl ester (CFSE)-staining for foetal cardiomyocytes. Staining for CD31 revealed a significant increase in vessel density in the infarction area compared with medium controls, possibly contributing to the benefit of transplanted foetal cardiomyocytes. Notably, a significant increase in the number of apoptotic cells was observed in cell-transplanted hearts accompanied by an increase in proliferation, collagen content and neutrophil infiltration, suggesting an active remodelling concomitant with sustained inflammatory processes. In conclusion, repetitive Tx of different cell types after myocardial infarction in rat hearts significantly improved left ventricular function and could represent a feasible option to enhance the benefit of cell therapy. PMID- 22050649 TI - Dr Jos? E Medina. PMID- 22050648 TI - Histological study of the extratympanic portion of the discomallear ligament in adult humans: a functional hypothesis. AB - This study was carried out on histological aspects of the extratympanic portion of the discomallear ligament (DL) in adult humans. The temporomandibular joint (TMJ) was dissected bilaterally in 20 cadavers; in 15 cases the articular disc (AD) and the retroarticular tissue were extirpated. The extratympanic portion of the DL had the shape of a base-down triangle, in relation to the AD, and an upper vertex, in relation to the petrotympanic fissure. In five cases, the base, measured bilaterally, had an average length of 6.4 mm, while the distance from the base to the upper vertex averaged 9.3 mm in length. The extratypanic portion of the DL is an intrinsic ligament of the TMJ, composed of collagen fibres and abundant elastic fibres. We propose that this ligament could act as a tensor of the synovial membrane in movements of the TMJ. PMID- 22050650 TI - Exponential Increase. PMID- 22050651 TI - Online Access. PMID- 22050652 TI - Potential role of statins on wound healing: review of the literature. AB - Wound healing is a dynamic and complex biological process, which requires coordinated events including haemostasis, inflammation, proliferation, revascularisation and remodelling. Impaired wound healing is a common problem that occurs in both community and hospital settings. Various experimental and clinical studies have evaluated different modalities for the treatment of topical wounds, such as sugar, antibiotics, honey and phytotherapies; also statins have diverse pleiotropic effects that have been suggested to be useful to improve wound healing. Data derived from both animal and human studies showed that statins especially atorvastatin, simvastatin and pravastatin can accelerate the wound-healing process. However, further high-quality and evidence-based studies are needed to address the best statin drug, appropriate dose, the best administration route, duration of treatment and to determine correlation between pleiotropic effects of statins and their probable clinical benefits. PMID- 22050653 TI - General health, health-related quality of life and sexual health after pediatric liver transplantation: a nationwide study. AB - The long-term impact of pediatric liver transplantation (LT) and its complications on general health, health-related quality of life (HRQoL) and sexual health were assessed. We conducted a national cross-sectional study of all pediatric recipients who underwent LT between 1987 and 2007. Of 66 survivors, 57 participants (86%) were compared to randomly chosen healthy controls (n = 141) at 10.7 +/- 6.6 years posttransplant. PedsQL4.0, SF-36, DISF-SR and AUDIT questionnaires for appropriate age groups were used. Patients and controls <7 years had similar HRQoL and 54% of patients aged over 7 scored within the controls' normal range on all HRQoL domains. In adult survivors, physical functioning and general health were decreased (p < 0.05). Biliary complications, reoperations and obesity were independently associated with reduced HRQoL (p < 0.05 for all). Still 64% of adult survivors considered their health excellent. Sexual health was similar to controls but LT recipients may experience problems with their orgasm strength (p = 0.050) and condom-based contraception was more common after LT than among controls (58% and 12%, p < 0.001). In conclusion, normal HRQoL and sexual health are achievable post-LT. PMID- 22050654 TI - Global source-receptor relationships for mercury deposition under present-day and 2050 emissions scenarios. AB - Global policies regulating anthropogenic mercury require an understanding of the relationship between emitted and deposited mercury on intercontinental scales. Here, we examine source-receptor relationships for present-day conditions and four 2050 IPCC scenarios encompassing a range of economic development and environmental regulation projections. We use the GEOS-Chem global model to track mercury from its point of emission through rapid cycling in surface ocean and land reservoirs to its accumulation in longer lived ocean and soil pools. Deposited mercury has a local component (emitted Hg(II), lifetime of 3.7 days against deposition) and a global component (emitted Hg(0), lifetime of 6 months against deposition). Fast recycling of deposited mercury through photoreduction of Hg(II) and re-emission of Hg(0) from surface reservoirs (ice, land, surface ocean) increases the effective lifetime of anthropogenic mercury to 9 months against loss to legacy reservoirs (soil pools and the subsurface ocean). This lifetime is still sufficiently short that source-receptor relationships have a strong hemispheric signature. Asian emissions are the largest source of anthropogenic deposition to all ocean basins, though there is also regional source influence from upwind continents. Current anthropogenic emissions account for only about one-third of mercury deposition to the global ocean with the remainder from natural and legacy sources. However, controls on anthropogenic emissions would have the added benefit of reducing the legacy mercury re-emitted to the atmosphere. Better understanding is needed of the time scales for transfer of mercury from active pools to stable geochemical reservoirs. PMID- 22050655 TI - Sorafenib monotherapy gives sustainable suppression of FLT3 clone in untreated patients with FLT3-internal tandem duplication positive acute myeloid Leukaemia. PMID- 22050656 TI - Belief in a Werther Effect: third-person effects in the perceptions of suicide risk for others and the moderating role of depression. AB - Werther Effect research has almost solely focused on the behavioral level of media effects. Clinically relevant predispositions like depression as well as the moderating role of media effects on a perceptional level have been omitted so far. To bridge this gap, we reanalyzed the data of an experiment conducted by Rustad, Small, Jobes, Safer, and Peterson: volunteer students' ratings for their self-risk of depression and suicide as well as their perceptions of others' suicide risk were investigated. While a Werther Effect could not be observed, there is a general overestimation of media influences on others--presumed Werther Effects--that are moderated by the personal degree of depression. PMID- 22050657 TI - Ectopic brain tissue in the retina of a beagle dog: a case report and literature review. AB - Isolated ectopic brain tissue within the orbit is an extremely rare finding and has never been reported in dogs or other domestic species. In this case, a focal choristoma of ectopic grey matter-like tissue was present within the retina of a mature female beagle dog, and consisted of neurons and astrocytes as demonstrated respectively by microtubule-associated protein 2 and glial fibrillary acidic protein immunohistochemistry. The lesion was located within the optic fundus adjacent to the optic disk and surrounded by dysplastic retina. The case is presented with a review of literature on this rare entity. PMID- 22050661 TI - Intraocular signet-ring cell melanoma in a hamster (Cricetulus griseus). AB - A two-and-a-half year-old male Chinese hamster (Cricetulus griseus) was referred for evaluation of an intraorbital mass involving the right eye. Based on ophthalmic examination and ultrasonography, a diagnosis of intraocular neoplasia was made. Enucleation of the affected eye was performed. The mass was histologically diagnosed as a primary malignant intraocular signet-ring cell melanoma. No signs of recurrence were detected, and the hamster remained clinically healthy until it died 6 months after surgery. This case report attempts to contribute to the limited body of knowledge available in the literature on primary intraocular neoplasms in hamsters. PMID- 22050662 TI - Carpal kinematics in quadrupedal monkeys: towards a better understanding of wrist morphology and function. AB - The purpose of this study is to provide new data on carpal kinematics in primates in order to deepen our understanding of the relationships between wrist morphology and function. To that end, we provide preliminary data on carpal kinematics in seven species of quadrupedal monkeys that have not been previously investigated in this regard (cercopithecoids, n = 4; ceboids, n = 3). We radiographed wrists from cadavers at their maximum radial and ulnar deviations, as well as at maximum flexion and extension. We took angular measurements to quantify the contribution of the mobility of the two main wrist joints (antebrachiocarpal and midcarpal) with respect to total wrist mobility. We also recorded qualitative observations. Our quantitative results show few clear differences among quadrupedal monkeys for radioulnar deviation and flexion extension: all the primates studied exhibit a greater midcarpal mobility (approximately 54-83% of the total range of motion) than antebrachiocarpal mobility; however, we identified two patterns of carpal kinematics that show the functional impact of previously recognised morphological variations in quadrupedal monkeys. Firstly, qualitative results show that the partition that divides the proximal joint of the wrist in ceboids results in less mobility and more stability of the ulnar part of the wrist than is seen in cercopithecoids. Secondly, we show that the olive baboon specimen (Papio anubis) is characterised by limited antebrachiocarpal mobility for extension; this effect is likely the result of a radial process that projects on the scaphoid notch, as well as an intraarticular meniscus. Because of these close relationships between carpal kinematics and morphology in quadrupedal monkeys, we hypothesise that, to some extent, these functional tendencies are related to their locomotor hand postures. PMID- 22050663 TI - Pancreatic cancer tumour initiating cells: the molecular regulation and therapeutic values. AB - Pancreatic cancer is an aggressive solid tumour characterized by its local invasion, early metastasis and resistance to standard chemotherapy or radiation therapy. Tumour initiating cells (TICs) are not only capable of self-renewal and differentiation, but also play an important role in multi-drug resistance, and thus become a popular topic in cancer research especially in pancreatic cancer. In this review, we summarize the current progress of TICs in tumourigenesis, various newly identified surface markers of pancreatic TICs, and the signalling pathways such as epithelial-mesenchymal transition, sonic hedgehog and Notch that regulate TICs. We also discuss the role which microRNA plays in TICs as well as its application in TIC-targeted therapy along with other approaches. PMID- 22050664 TI - Bioenergetics of T cell activation and death in HIV type 1 infection. AB - Regressive morphological lesions, found in peripheral lymphocytes from HIV(+) patients, clearly conflict with normal cycle progression and with the execution of basic housekeeping and immune functions. With these lesions, circulating lymphocytes are destined to spontaneous and energy-independent cell lysis. By means of confocal microscopy and morphometry, we have quantified the rate of circulating T cells that are probably destined to emocatheresis in vivo. This rate includes lymphocytes in which nucleolin fragments have been scattered out of the nuclear region as a result of prelethal alterations in the nuclear membrane permeability. In terms of bioenergetics, these cells show evident anomalies in the energy production machinery that make them unable to carry out ATP-requiring functions. The extent of damaged cell fraction in peripheral blood reflects the frequency with which T lymphocytes leave lymphoid tissue to be cleared in hemocatheretic processes. PMID- 22050665 TI - Changes in anticonvulsant prescribing for Australian children: implications for Quality Use of Medicines. AB - AIMS: The evidence-base guiding choices between newer versus established anticonvulsants in children is limited. Inappropriate use exposes children to potentially ineffective and/or harmful medicines. Our objective is to describe recent anticonvulsant prescribing patterns in the Australian paediatric population, evaluating overall trends and extent of off-label prescribing of newer agents. METHODS: Aggregated national data on 15 anticonvulsants with Pharmaceutical Benefits Scheme subsidy dispensed by community pharmacies for children aged <16 years were obtained from the Drug Utilisation Subcommittee, which is part of the Australian Government Department of Health and Ageing. We analysed trends for the five most prescribed anticonvulsants dispensed between 2002 and 2009 and off-label prescribing for agents where approved Australian product information stipulates a minimum age. RESULTS: Valproate was the most frequently prescribed anticonvulsant with no marked change in prescription numbers per 1000 children aged 0-16 years (11.3-11.8 prescriptions/year). Lamotrigine was the most frequently prescribed newer anticonvulsant (7.9-9.3 prescriptions/year). Carbamazepine prescriptions decreased by 38% and topiramate prescriptions increased by 19% over the 7-year study period; 3.6% of topiramate prescriptions were off-label (by age) for children aged <2 years. Since Pharmaceutical Benefits Scheme listing in 2003, levetiracetam prescriptions increased steeply to 2.5 prescriptions/year per 1000 children in 2009; 4.2% were off-label for children aged <4 years. CONCLUSIONS: The substantial reduction in carbamazepine use and corresponding increase in newer anticonvulsant prescribing, including off-label uses, raises questions about potentially suboptimal Quality Use of Medicines. Such major changes in prescribing may have important clinical and economic consequences. Further study to better understand paediatric prescribing choices and outcomes is needed. PMID- 22050666 TI - Managing acute respiratory decompensation in the morbidly obese. AB - Morbid obesity adversely affects respiratory physiology, leading to reduced lung volumes, decreased lung compliance, ventilation perfusion mismatch, sleep disordered breathing and the impairment of ventilatory control, and neurohormonal and neuromodulators of breathing. Therefore, morbidly obese subjects are at increased risk of various pulmonary complications that can present either acutely or chronically. Respiratory failure is one of the most common pulmonary complications related to morbid obesity. Both acute hypoxaemic and hypercapnic respiratory failure are more common among obese patients. The management pathway of respiratory failure depends, to a large extent, on the underlying cause, primarily due to the diversity of the underlying triggering diseases, the pathophysiology and the prognosis associated with each disease. Morbidly obese patients with hypoventilation have an increased risk of acute hypercapnic respiratory failure. Early diagnosis of this disorder and the application of non invasive ventilation in this group of patients have been shown to improve respiratory parameters, decrease the need for invasive mechanical ventilation and improve survival. Invasive ventilation remains the last life-saving procedure in patients with respiratory failure who do not respond to non-invasive measures. However, due to the abnormal respiratory physiology in obese patients, special precautions are required during intubation, mechanical ventilation and weaning. PMID- 22050667 TI - Tunable bandgap in silicene and germanene. AB - By using ab initio calculations, we predict that a vertical electric field is able to open a band gap in semimetallic single-layer buckled silicene and germanene. The sizes of the band gap in both silicene and germanene increase linearly with the electric field strength. Ab initio quantum transport simulation of a dual-gated silicene field effect transistor confirms that the vertical electric field opens a transport gap, and a significant switching effect by an applied gate voltage is also observed. Therefore, biased single-layer silicene and germanene can work effectively at room temperature as field effect transistors. PMID- 22050668 TI - Alcohol consumption and female urinary incontinence: a community-based study in Japan. AB - OBJECTIVES: To investigate the association between alcohol consumption and urinary incontinence among Japanese women. METHODS: A total of 300 women aged 40 75 years were recruited from the community in middle and southern Japan. A validated food frequency questionnaire was given face-to-face to obtain information on dietary intake and habitual alcohol consumption. Urinary incontinence status was ascertained using the International Consultation on Incontinence Questionnaire-Short Form. RESULTS: Among the 298 eligible participants, 82 women (27.5%) experienced urine leakage. The prevalence of alcohol drinking and mean ethanol intake were slightly higher among the incontinent women (39%; 7.1, standard deviation 24.1 g/day) than others without the condition (35.6%; 4.3, standard deviation 10.7 g/day). Relative to non drinkers, the adjusted odds ratios of urinary incontinence were 1.31 (95% confidence interval 0.74-2.33) for alcohol drinking and 1.69 (95% confidence interval 0.42-6.81) for ethanol intake over 32 g/day, though the increases in risk did not reach statistical significance. CONCLUSIONS: Little association is evident between alcohol consumption and urinary incontinence in middle-aged and older Japanese women. Further studies are required to define the role of alcohol as a contributing factor of this distressing condition. PMID- 22050669 TI - Feline calicivirus: a neglected cause of feline ocular surface infections? AB - OBJECTIVE: To investigate the prevalence of feline calicivirus (FCV) infection in relation to ocular surface lesions in cats with upper respiratory tract diseases (URTD). ANIMALS STUDIED: Ninety-nine cats with ocular surface infection and symptoms or recent history of URTD were examined at various rescue shelters and hospitals. PROCEDURE: A complete general and ophthalmic examination was performed including Schirmer tear test, slit-lamp biomicroscopy, fluorescein and lissamine green staining. Clinical and ocular symptoms were scored and recorded. Conjunctival samples were collected using a cytobrush, and nucleic acid extraction using RT-PCR was carried out to analyze for the presence of various infectious agents. RESULTS: RT-PCR detected either FCV, feline herpes virus type 1 (FHV-1), Chlamydophila felis or Mycoplasma spp. in 63/99 samples. 30/63 samples were positive for FCV, 23/63 for C. felis, 21/63 for Mycoplasma spp., and 16/63 for FHV-1. Out of the 30 FCV-positive samples, 11 were positive only for FCV and in 19 samples FCV was seen in combination with other agents. FCV infection was highest in animals examined at the rescue centers and in the age group of 0-2 months. Erosive conjunctivitis was an important ocular finding. Oral ulcers were detected in all FCV-infected cats. CONCLUSION: Results indicate that FCV is highly prevalent in cats with URTD either as a sole infectious agent or in combination with other pathogens and therefore is a potential cause for ocular surface lesions during the URTD. PMID- 22050672 TI - Corrections. PMID- 22050673 TI - Male gender predicts mortality in a large cohort of patients receiving antiretroviral therapy in Uganda. AB - BACKGROUND: Because men in Africa are less likely to access HIV/AIDS care than women, we aimed to determine if men have differing outcomes from women across a nationally representative sample of adult patients receiving combination antiretroviral therapy in Uganda. METHODS: We estimated survival distributions for adult male and female patients using Kaplan-Meier, and constructed multivariable regressions to model associations of baseline variables with mortality. We assessed person-years of life lost up to age 55 by sex. To minimize the impact of patient attrition, we assumed a weighted 30% mortality rate among those lost to follow up. RESULTS: We included data from 22,315 adults receiving antiretroviral therapy. At baseline, men tended to be older, had lower CD4 baseline values, more advanced disease, had pulmonary tuberculosis and had received less treatment follow up (all at p < 0.001). Loss to follow up differed between men and women (7.5 versus 5.9%, p < 0.001). Over the period of study, men had a significantly increased risk of death compared with female patients (adjusted hazard ratio 1.43, 95% CI 1.31-1.57, p < 0.001). The crude mortality rate for males differed importantly from females (43.9, 95% CI 40.7-47.0/1000 person-years versus 26.9, 95% CI 25.4-28.5/1000 person years, p < 0.001). The probability of survival was 91.2% among males and 94.1% among females at 12 months. Person-years of life lost was lower for females than males (689.7 versus 995.9 per 1000 person-years, respectively). CONCLUSIONS: In order to maximize the benefits of antiretroviral therapy, treatment programmes need to be gender sensitive to the specific needs of both women and men. Particular efforts are needed to enroll men earlier into care. PMID- 22050675 TI - QSPR models for computer-aided drug design in microbiology, parasitology, and pharmacology. PMID- 22050677 TI - Deterministic and stochastic model for the role of the immune response time delay in periodic therapy of the tumors. AB - We consider the deterministic model of interaction between the immune system and tumor cells including a memory function that reflects the influence of the past states, to simulate the time needed by the latter to develop a chemical and cell mediated response to the presence of the tumor. The memory function is called delay kernel. The results are compared with those from other papers, concluding that the memory function introduces new instabilities in the system leading to an uncontrollable growth of the tumor. If the coefficient of the memory function is used as a bifurcation parameter, it is found that Hopf bifurcation occurs for kernel. The direction and stability of the bifurcating periodic solutions are determined. The deterministic model with delay allows stochastic perturbation. Mean value and square mean value of the linearized model are analyzed for the variables of the stochastic model. Some numerical simulations for justifying the theoretical analysis are also given. PMID- 22050676 TI - Review of QSAR for DNA polymerase inhibitors and new models for heterogeneous series of compounds. AB - DNA polymerases are essential enzymes for DNA replication, repair and recombination. The high number of possible candidates creates the necessity of Quantitative Structure-Activity Relationship models in order to guide the DNA polymerase inhibitors. In this work, we revised different computational studies for a very large and heterogeneous series of DNA polymerase inhibitors. First, we reviewed QSAR methods with different compounds to find out the structural requirements for DNA polymerase inhibitory activity. Last, we report a new LDA analysis with the different molecular descriptors calculated with DRAGON software. PMID- 22050674 TI - Identification of common and cell type specific LXXLL motif EcR cofactors using a bioinformatics refined candidate RNAi screen in Drosophila melanogaster cell lines. AB - BACKGROUND: During Drosophila development, titers of the steroid ecdysone trigger and maintain temporal and tissue specific biological transitions. Decades of evidence reveal that the ecdysone response is both unique to specific tissues and distinct among developmental timepoints. To achieve this diversity in response, the several isoforms of the Ecdysone Receptor, which transduce the hormone signal to the genome level, are believed to interact with tissue specific cofactors. To date, little is known about the identity of these cofactor interactions; therefore, we conducted a bioinformatics informed, RNAi luciferase reporter screen against a subset of putative candidate cofactors identified through an in silico proteome screen. Candidates were chosen based on criteria obtained from bioinformatic consensus of known nuclear receptor cofactors and homologs, including amino acid sequence motif content and context. RESULTS: The bioinformatics pre-screen of the Drosophila melanogaster proteome was successful in identifying an enriched putative candidate gene cohort. Over 80% of the genes tested yielded a positive hit in our reporter screen. We have identified both cell type specific and common cofactors which appear to be necessary for proper ecdysone induced gene regulation. We have determined that certain cofactors act as co-repressors to reduce target gene expression, while others act as co activators to increase target gene expression. Interestingly, we find that a few of the cofactors shared among cell types have a reversible roles to function as co-repressors in certain cell types while in other cell types they serve as co activators. Lastly, these proteins are highly conserved, with higher order organism homologs also harboring the LXXLL steroid receptor interaction domains, suggesting a highly conserved mode of steroid cell target specificity. CONCLUSIONS: In conclusion, we submit these cofactors as novel components of the ecdysone signaling pathway in order to further elucidate the dynamics of steroid specificity. PMID- 22050678 TI - Current drug design of anti-HIV agents through the inhibition of C-C chemokine receptor type 5. AB - Human immunodeficiency virus (HIV) is the responsible causal agent of acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, allowing the entry of opportunistic infections. HIV infection in humans is considered pandemic by the World Health Organization (WHO). HIV needs to use a protein as a co-receptor to enter its target cells. Several chemokine receptors can in principle act as viral co-receptors, but the chemokine (C-C motif) receptor 5 (CCR5) is likely the most physiologically important co-receptor during natural infection. For this reason the development of new CCR5 inhibitors like anti-HIV agents, constitutes a challenge for the scientific community. The present review will focus on the current state of the design of novel anti-HIV drugs, and how the existing computer aided-drug design methodologies, have been effective in the search of new anti-HIV agents. In addition, a QSAR model based on substructural descirptors is presented as a rapid, rational and promising alternative for the discovery of anti-HIV agents through the inhibition of the CCR5. PMID- 22050679 TI - Current computational approaches towards the rational design of new insecticidal agents. AB - Pesticides are chemicals with a great impact in the economy of any country. They are employed for the eradication of pests. Insects constitute one of these pests which are extremely difficult to control. With the passage of the time, insects have become resistant to pesticides, causing huge crop losses and diseases in humans. For this reason, there is an increasing need for the design of more potent insecticides. The present review is focused on the current state of the application of computational approaches as essential tools for the design of novel insecticidal agents. Also, a model based on a substructural approach is presented as a rational, efficient and promising alternative for the discovery of new insecticides. PMID- 22050680 TI - Computational models for 5alphaR inhibitors for treatment of prostate cancer: review of previous works and screening of natural inhibitors of 5alphaR2. AB - Taking into consideration the high importance of the drug target 5-alpha reductase (5alphaR) in prostate cancer in this work we are going first to review previous works and discuss works related to the computer aided drug design of 5alphaR inhibitors. We report new results in the in silico screening of natural 5alphaR inhibitors. Traditionally, drugs were discovered by testing compounds synthesized in time consuming multi-step processes against a battery of in vivo biological screens. Promising compounds were then further studied in development, where their pharmacokinetic properties, metabolism and potential toxicity were investigated. Here we present a study on herbal lead compounds and their potential binding affinity to the effectors molecules of major disease like Prostate Cancer. Clinical studies demonstrate a positive correlation between the extent of 5alphaR type 2 (5alphaR2) and malignant progression of precancerous lesions in prostate. Therefore, identification of effective, well-tolerated 5alphaR inhibitors represents a rational chemo preventive strategy. This study has investigated the effects of naturally occurring non-protein compounds berberine and monocaffeyltartaric acid that inhibits 5alphaR type2. Our results reveal that these compounds use less energy to bind to 5alphaR and inhibit its activity. Their high ligand binding affinity to 5alphaR introduce the prospect for their use in chemopreventive applications; in addition they are freely available natural compounds that can be safely used to prevent prostate cancer. PMID- 22050681 TI - Revision of QSAR, docking, and molecular modeling studies of anti-influenza virus A (H1N1) drugs and targets: analysis of hemagglutinins 3D structure. AB - Recently WHO and NREVSS collaborating laboratories located in all 50 states, and Washington D.C reported that out of 3,588 specimens,164 were found positive for influenza type (i.e. 4.6%) and from these 164 specimens 162 (i.e. 98.8 %) were of influenza A H1N1 subtype. Comparative study of the past and current reports gives a general idea that the influenza activity deserves high attention from public health authorities in the U.S. In this connection, presently some groups are developing intensive computer-aided research in QSAR, Docking, Molecular Modeling and Drug Design, Sequence Analysis and Phylogenetic analysis of candidate compounds and/or targets; in order to advance in the treatment and/or prevention of this pandemic Flu. In this work, primarily we carry out a mini-review of the more important theoretical studies reported until now within this area, followed by the study of a specific type of target. Keeping in view the nature of this virus, we can conclude that there is always a need to find other target protein as inhibitor other than the existing one. So that this lethal pandemic flu can be treated and prevented further. Therefore, after Neuraminidase and M2 ion channels the surface protein that we can target in H1N1 strain is Hemagglutinins (HA). We use comparative modeling; which is one of the methods that can reliably generate a 3D model for HA protein. Multiple structures of this subtype of Influenza Virus are available at PDB, but we are focused on Influenza A (H1N1). Therefore, methodology of analysis mainly focuses on modeling the structure of this protein and, if possible, finding a probable active sites and inhibitors to it. PMID- 22050682 TI - Review of synthesis, biological assay and QSAR studies of beta-secretase inhibitors. AB - Alzheimer's disease (AD) is highly complex. While several pathologies characterize this disease, amyloid plaques, composed of the beta-amyloid peptide, are hallmark neuropathological lesions in Alzheimer's disease brain. Indeed, a wealth of evidence suggests that beta-amyloid is central to the pathophysiology of AD and is likely to play an early role in this intractable neurodegenerative disorder. The BACE-1 enzyme is essential for the generation of beta-amyloid. BACE 1 knockout mice do not produce beta-amyloid and are free from Alzheimer's associated pathologies, including neuronal loss and certain memory deficits. The fact that BACE-1 initiates the formation of beta-amyloid, and the observation that BACE-1 levels are elevated in this disease provide direct and compelling reasons to develop therapies directed at BACE-1 inhibition, thus reducing beta amyloid and its associated toxicities. In this sense, quantitative structure activity relationships (QSAR) could play an important role in studying these beta secretase inhibitors. QSAR models are necessary in order to guide the beta secretase synthesis. This work is aimed at reviewing different design and synthesis and computational studies for a very large and heterogeneous series of beta-secretase inhibitors. First, we review design, synthesis, and Biological assay of beta-secretase inhibitors. Next, we review 2D QSAR, 3D QSAR, CoMFA, CoMSIA and Docking with different compounds to find out the structural requirements. Next, we review QSAR studies using the method of Linear Discriminant Analysis (LDA) in order to understand the essential structural requirement for receptor binding for beta- secretase inhibitors. PMID- 22050683 TI - From chemical graphs in computer-aided drug design to general Markov-Galvez indices of drug-target, proteome, drug-parasitic disease, technological, and social-legal networks. AB - Complex Networks are useful in solving problems in drug research and industry, developing mathematical representations of different systems. These systems move in a wide range from relatively simple graph representations of drug molecular structures to large systems. We can cite for instance, drug-target protein interaction networks, drug policy legislation networks, or drug treatment in large geographical disease spreading networks. In any case, all these networks have essentially the same components: nodes (atoms, drugs, proteins, microorganisms and/or parasites, geographical areas, drug policy legislations, etc.) and edges (chemical bonds, drug-target interactions, drug-parasite treatment, drug use, etc.). Consequently, we can use the same type of numeric parameters called Topological Indices (TIs) to describe the connectivity patterns in all these kinds of Complex Networks despite the nature of the object they represent. The main reason for this success of TIs is the high flexibility of this theory to solve in a fast but rigorous way many apparently unrelated problems in all these disciplines. Another important reason for the success of TIs is that using these parameters as inputs we can find Quantitative Structure Property Relationships (QSPR) models for different kind of problems in Computer Aided Drug Design (CADD). Taking into account all the above-mentioned aspects, the present work is aimed at offering a common background to all the manuscripts presented in this special issue. In so doing, we make a review of the most common types of complex networks involving drugs or their targets. In addition, we review both classic TIs that have been used to describe the molecular structure of drugs and/or larger complex networks. Next, we use for the first time a Markov chain model to generalize Galvez TIs to higher order analogues coined here as the Markov-Galvez TIs of order k (MGk). Lastly, we illustrate the calculation of MGk values for different classes of networks found in drug research, nature, technology, and social-legal sciences. PMID- 22050684 TI - Selective cholinesterase inhibitors from Buxus sempervirens L. and their molecular docking studies. AB - In this work, two alkaloids namely (+)-buxabenzamidienine (1) and (+)-buxamidine (2) were isolated from Buxus sempervirens, using bioassay-guided fractionation and isolation method. Their acetyl- (AChE) and butyrylcholinesterase (BChE) inhibitory activities were studied and the compounds were found to be quite selective inhibitors of AChE. IC50 values of compound 1 for electric eel AChE and horse BChE were 0.787 and 7.68 mM, respectively; while the corresponding IC50 of compound 2 were 1.70 and 549.98 mM, respectively. Theoretical (quantum mechanical, homology modelling and docking) calculations were performed in order to explain their interactions with different AChE (electric eel and human) and BChE (horse and human). The x-ray crystal structures of electric eel AChE, human AChE, human BChE and a model of horse BChE constructed by homology with human BChE were used for docking of compounds 1 and 2. Density functional theory (DFT) calculations of the compounds were performed at the B3LYP/6- 31G** level using the program SpartanTM, and their HOMO and LUMO energy levels were calculated. Docking studies exhibited that compound 1 interacts with the acyl-binding pocket of the active site gorge of huAChE, and including several other hydrophobic interactions. PMID- 22050685 TI - Review of computer-aided models for predicting collagen stability. AB - Collagen is the most abundant protein in the whole human body and its instability is involved in many important diseases, such as Osteogenesis imperfecta, Ehlers Danlos syndrome, and collagenopathy. The stability of the collagen triple helix is strictly related to its amino acid sequence, especially the main Gly-X-Y motif. Many groups have used computational methods to investigate collagen's structure and the relationship between its stability and structure. In this study, we initially reviewed the most important computational methods that have been applied in this field. We then assembled data on a large number of collagen like peptides to build the first Markov chain model for predicting the stability of the collagen at different temperatures, simply by analyzing the amino acid sequence. We used the literature to assemble a set of 102 peptides and their relative melting temperatures were determined experimentally, indicating a great variance with the main motif of the collagen. This dataset was then split in two classes, stable and unstable, according to their melting temperatures and the dataset was then used to build artificial neural network (ANN) models to predict collagen stability. We built models to predict stability at temperatures of 38 degrees C, 35 degrees C, 30 degrees C, and 25 degrees C degrees, and all models had an accuracy between 82% and 92%. Several cross-validation procedures were performed to validate the model. This method facilitates fast and accurate predictions of collagen stability at different temperatures. PMID- 22050686 TI - Different patient subgroup, different ranking? Which quality indicators do patients find important when choosing a hospital for hip- or knee arthroplasty? AB - BACKGROUND: Patients are increasingly expected to become active, critical consumers in healthcare. They can use comparative healthcare information presented on websites to make informed choices for healthcare providers. However, the use of this information has been limited so far. An obstacle can be that the information is not perceived as relevant by patients. Presenting only the most important quality indicators might improve the usefulness of this information. The aim of this study was to explore which quality indicators different subgroups of patients find important when choosing a hospital for total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: In this explorative, cross sectional study, questionnaires were distributed to 265 patients who underwent or had to undergo THA/TKA. Participants were asked to rank the importance of three types of quality indicators: patient experience indicators, clinical performance indicators, and indicators about hospital services. We used random effects regression analyses to assess the relative importance of the indicators in different subgroups of patients. RESULTS: 110 patients (response rate 41.5%) who underwent or had to undergo THA/TKA participated. Conduct of doctors, the presence of procedures to prevent adverse effects of thrombosis and information about the specialist area of orthopaedists were the most important patient experience indicator, clinical performance indicator and indicator about hospital services, respectively. We found a few differences between patient subgroups in the importance attached to the quality indicators. CONCLUSIONS: This study provides a first insight into which quality indicators patients find important when choosing a hospital for THA/TKA, and shows that subgroups of patients differ in the value they attach to these indicators. More extended research is needed to establish the indicators that should at least be presented in succinct overviews of comparative healthcare information for patients choosing a hospital for THA/TKA. PMID- 22050687 TI - Dose response for travoprost(r) in the glaucomatous beagle. AB - OBJECTIVE: To evaluate the changes in intraocular pressure (IOP) and pupil size in 12 Beagles with inherited glaucoma after instillations of 0.033, 0.0033, 0.001, 0.00033, and 0.0001% travoprost (Travatan(r)-Alcon Laboratories, Inc., Ft Worth, TX, USA) in multiple single-dose studies. PROCEDURES: Intraocular pressure and pupil diameter (PD) measurements were obtained at 9 am, 12 pm, 3 pm, and 9 am the following day (24 h) in two groups of six glaucoma dogs. After 7 days, the vehicle or concentration was repeated in the contralateral eye of the same animals. RESULTS: Concentrations of 0.00033, 0.001, and 0.0033% travoprost significantly lowered IOP and PD, but the 0.0001% concentration provided limited IOP changes, although PD changes were still significant. This suggests travoprost is effective in the dog to lower IOP and reduce pupil size at concentrations starting between 0.0001 and 0.00033%. CONCLUSIONS: The dose response for travoprost in the glaucomatous Beagle indicates this model is highly sensitive to this group of drugs, even at concentrations as low as 0.00033% (1/12 the commercially available concentration). PMID- 22050688 TI - Effect of diesel oxidation catalysts on the diesel particulate filter regeneration process. AB - A Diesel Particulate Filter (DPF) regeneration process was investigated during aftertreatment exhaust of a simulated diesel engine under the influence of a Diesel Oxidation Catalyst (DOC). Aerosol mass spectrometry analysis showed that the presence of the DOC decreases the Organic Carbon (OC) fraction adsorbed to soot particles. The activation energy values determined for soot nanoparticles oxidation were 97 +/- 5 and 101 +/- 8 kJ mol(-1) with and without the DOC, respectively; suggesting that the DOC does not facilitate elementary carbon oxidation. The minimum temperature necessary for DPF regeneration was strongly affected by the presence of the DOC in the aftertreatment. The conversion of NO to NO(2) inside the DOC induced the DPF regeneration process at a lower temperature than O(2) (DeltaT = 30 K). Also, it was verified that the OC fraction, which decreases in the presence of the DOC, plays an important role to ignite soot combustion. PMID- 22050689 TI - MBL2 and fever during neutropenia in children with acute lymphoblastic leukaemia. PMID- 22050690 TI - Effect of acute intraocular pressure elevation on blood flow velocity and resistance in the rabbit ophthalmic artery. AB - OBJECTIVE: To determine the effect of intraocular pressure (IOP) on blood flow velocity and resistance in the rabbit ophthalmic artery. ANIMALS: Ten adult New Zealand White rabbits were used. PROCEDURES: Right eyes were cannulated and the IOP was raised in a stepwise manner from 20 to 70 mmHg. Peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI) in the ophthalmic artery were measured by color Doppler imaging. Values of PSV, EDV and RI were compared at various IOPs via the analysis of variance (anova) of a randomized block design with post hoc Bonferroni test. RESULTS: Significant differences of PSV, EDV and RI at different IOP points (all P < 0.001) were observed. Over the entire IOP range, linear regression showed a negative correlation between IOP and both PSV and EDV (beta = -0.07434, P = 0.0020 and beta = -0.07829, P < 0.001, respectively), as well as a positive correlation between the RI and IOP (beta = 0.00221, P < 0.001). Moreover, line plots identified a point with IOP = 40 mmHg, splitting the IOP range with different regression slopes. Piecewise linear regression indicated no correlation between PSV, EDV, RI and IOP when the IOP was elevated from 20 to 40 mmHg (P = 0.1832, P = 0.5932 and P = 0.5819, respectively). However, piecewise linear regression detected a stronger negative correlation between PSV, EDV and IOP (beta = -0.15760, P = 0.0011 and beta = 0.11872, P = 0.001, respectively) and a stronger positive correlation between RI and IOP (beta = 0.00273, P = 0.0015) during the stage from 40 to 70 mmHg. CONCLUSIONS: The ophthalmic artery in the rabbits was capable of maintaining normal blood velocity and resistance when IOP was below 40 mmHg. However, the autoregulatory capacity was greatly limited when IOP was over 40 mmHg. PMID- 22050691 TI - Involvement of COX-2/PGE2 signalling in hypoxia-induced angiogenic response in endothelial cells. AB - To evaluate the impact of hypoxia on the angiogenic capability of endothelial cells (ECs), and further investigate whether the cyclooxygenase-2 (COX 2)/prostaglandin E(2) (PGE(2)) signalling is involved in the angiogenic response of ECs to hypoxia. We explored the impact of various periods (1, 3, 6, 12, 24 hrs) of hypoxia (2% O(2)) on human umbilical vein endothelial cells (HUVECs) in vitro. We observed cell viability, migration, tube formation, analysed COX-2, vascular endothelial growth factor (VEGF), AQP1 mRNA transcription, protein expression and measured PGE(2), VEGF protein concentration in cell supernatants. Then we treated HUVECs with COX-2 selective inhibitor NS398, EP1/2 combined antagonist AH6809 and exogenous PGE(2) to investigate the role of COX-2/PGE(2) signalling in the angiogenic response of ECs to hypoxia. The results demonstrated that short-term hypoxic treatment enhanced HUVECs proliferation, migration, tube formation, significantly up-regulated COX-2, VEGF, AQP1 mRNA level, protein expression and promoted PGE(2) , VEGF release. The pharmacological inhibition study revealed that exposure of HUVEC to NS398 and AH6809 under hypoxia impaired the biological responses of ECs to hypoxia. Exogenous PGE(2) augments the effects of hypoxia on HUVECs, and partially reversed the inhibitory effects of NS398 on HUVECs proliferation and angiogenic capability. Short-term hypoxic treatment enhanced angiogenic capability of ECs, and COX-2/PGE(2) signalling may play a critical role in the biological response of ECs to hypoxia. PMID- 22050692 TI - Visualising difference, similarity and belonging in paediatric genetics. AB - Paediatric genetics is increasingly playing a role in explorations of why a child may not be reaching developmental milestones, while experiencing various health concerns and displaying unusual physical characteristics. The diagnostic processes include close analyses of a child's body in order to identify 'clues' to possible genetic variation. When the genetic variation identified is new and complex there is significant uncertainty about what relationship that variation has to childhood development and what it will mean for a child's future. This paper, drawing from an ethnographic study of a genetics clinic, explores what versions of childhood difference and normality are produced by genetic explorations marked by uncertainty. The focus is on the significance of visual dynamics within the consultation, in family stories or photographs, and in the images found on websites which catalogue genetic syndromes. Our argument is that inside and outside the clinic the visual interpretations create understandings of the child that at times position him or her as 'other', while at other times recognise the child as normal and 'one of us'. The uncertainty embedded in identifying rare genetic variations enables multiple interpretations to emerge which do not 'fix' the child into the category of the 'genetically other'. PMID- 22050693 TI - Report of two cases of influenza virus A/H1N1v and B co-infection during the 2010/2011 epidemics in the Italian Veneto Region. AB - From October 2010 to April 2011, in the Italian Veneto Region, 1403 hospitalized patients were tested for influenza virus infection by specific real time RT-PCR. Overall, 327 samples were positive for either influenza A (75%) or B (25%) viruses. Among these positive patients two resulted co-infected by A/H1N1v and B viruses. Even though co-infection with both influenza A and B viruses appears to be a rare event, it occurs naturally and may play a role in epidemiology and pathogenicity. In the present study the two co-infected patients were a transplant recipient immunocompromised adult and a child displaying a severe respiratory illness. The co-infection was confirmed by inoculation of the nasopharyngeal swabs in MDCK.2 cells, followed by immunofluorescence and real time RT-PCR assays. Moreover, in the case of the adult patient, the immune system response against both viruses was assayed by hemoagglutination inhibition test against reference influenza virus strains. Both patients fully recovered from infection, without significant differences with mono-infected patients. PMID- 22050694 TI - The effects of immobilization on vascular canal orientation in rat cortical bone. AB - It is well established that bone is capable of adapting to changes in loading; however, little is known regarding how loading specifically affects the internal 3D microarchitecture of cortical bone. The aim of this study was to experimentally test the hypothesis that loading is a determinant of the 3D orientation of primary vascular canals in the rat tibial diaphysis. Left tibiae from 10 rats (30 weeks old) that had been immobilized (sciatic neurectomy) for 27 weeks, right SHAM-operated tibiae from these same rats (internal control) and right tibiae from 10 normal age-matched rats (external control) were scanned by micro-CT. Mean canal orientation (for the whole bone segment and by region), percent porosity, canal diameter and canal separation were quantitatively assessed in 3D. Canal orientation in the immobilized tibiae was significantly (P < 0.001) more radial (by 9.9 degrees ) compared to the external controls but did not differ from the internal controls (P = 0.310). Comparing the external and internal controls, orientation was significantly (P < 0.05) more radial in the internal control group (by 6.8 degrees ). No differences were found for percent porosity and canal separation. Canal diameter was significantly greater in the immobilized vs. internal (P < 0.001) and external control (P < 0.001) tibiae. The differences in orientation relative to the external controls indicated that the organization of cortical bone in the rat is affected by loading. Although the predicted difference in canal orientation was not detected between immobilized and internal control groups, the distributions of individual canal orientations, from which the mean values were derived, revealed distinctive patterns for all three groups. The internal controls exhibited an intermediate position between the immobilized and external controls, suggesting that paralysis on the contralateral side resulted in altered loading relative to the normal state represented by the external control. This was also evident in a regional analysis by quadrant. The loaded bones had the same cross-sectional shape; however, their internal structure differed. These results provide novel insights into the impact of loading on the 3D organization of primary cortical bone and have implications for understanding the relation between cortical bone adaptation, disease and mechanical properties. PMID- 22050695 TI - Effects of HAART on platelet-activating factor metabolism in naive HIV-infected patients I: study of the tenofovir-DF/emtricitabine/efavirenz HAART regimen. AB - Platelet-activating factor (PAF) is implicated in human immunodeficiency virus (HIV)-related manifestations. Increased PAF synthesis has been recently detected in HIV-infected patients. In this study, we examined in naive HIV-infected patients the in vivo effects of a highly active antiretroviral therapy (HAART) regimen, containing tenofovir-DF/emtricitabine/efavirenz, on PAF metabolism. The specific activities of PAF basic biosynthetic enzymes, PAF cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (lyso-PAF-AT), but also the ones of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets, and lipoprotein-associated-phospholipase-A(2) (LpPLA(2)) in plasma, were measured in blood samples of eight asymptomatic naive male HIV-infected patients just before and after 1, 3, and 6 months of treatment. CD4 cell counts, viral load, and several biochemical markers were also measured in the same blood samples of these patients. The repeated measures ANOVA and the Pearson r criterion were used to study statistical differences and correlations partial correlations, while linear mixed models were conducted in order to estimate association(s) between time-dependent changes in these factors. Before treatment, the activities of PAF-CPT in leukocytes and LpPLA(2) in plasma were found to be inversely correlated with CD4 cell counts and positively correlated with the viral load. After 6 months of treatment, the activities of basic PAF biosynthetic enzymes, PAF-CPT and lyso-PAF-AT, were both reduced in leukocytes. At 6 months, PAF-AH activity was also reduced in these cells, while LpPLA(2) remained stable. The reduction of PAF-CPT occurred even from the first month, while there is a time-dependent correlation between the increase of CD4 and the decrease of both viral load and PAF-CPT of leukocytes during treatment. Apart from its classical antiretroviral activities the tenofovir DF/emtricitabine/efavirenz regimen also exhibited favorable effects on PAF metabolism and therefore may also display beneficial effects in some HIV-related conditions, such as cardiovascular disease (CVD), in which PAF is implicated. PMID- 22050696 TI - Editorial comment to Impact of the tumor enhancement pattern in computed tomography for the differential diagnosis of renal cell carcinoma and benign renal tumor. PMID- 22050697 TI - George C Paffenbarger Student Research Award. PMID- 22050699 TI - Operative Dentistry Home Page. PMID- 22050700 TI - Effects of an unfixed combination of latanoprost and pilocarpine on the intraocular pressure and pupil size of normal dogs. AB - OBJECTIVE: To assess changes in intraocular pressure (IOP) and pupil diameter (PD) induced by daily application of an unfixed combination of latanoprost and pilocarpine in normal dogs. ANIMALS STUDIED: Fifteen mixed breed clinically normal dogs of both sexes. PROCEDURES: Three groups of five dogs each were administered in the right eye, one drop of 0.005% latanoprost (group L), 2% pilocarpine (group P), and 0.005% latanoprost with 2% pilocarpine (group LP), respectively. The left eyes received placebo. Drugs were administered once a day at 8 a.m. over a period of 5 days. IOP and PD measurements were conducted daily at 8 a.m., 10 a.m., 12 noon, 2 p.m., and 4 p.m. from 1 day preceding treatment to 7 days following treatment, and the presence of blepharospasm and/or conjunctival hyperemia was noted. RESULTS: Compared to baseline values, mean diurnal IOPs significantly decreased during the treatment period, by 4.4 (24.4%), 5.8 (31.4%), and 6.1 mmHg (35%) in the L, P, and LP groups, respectively. Compared to placebo treated eyes, reductions of 2.1(14.1%), 3.2 (20.1%), and 4.1 mmHg (26.6%) were observed for the L, P, and LP groups, respectively. Although mean IOPs in the LP group decreased slightly more than the other two groups, these differences were not statistically significant. Miosis and conjunctival hyperemia were observed in the treated eyes of all three groups of animals during the treatment period. CONCLUSIONS: Although both 0.005% latanoprost and 2% pilocarpine individually produced significant decrease in IOP, the topical administration of a combination of latanoprost (0.005%) and pilocarpine (2%) was not associated with a statistically significant synergistic reduction in IOP in dogs; and miosis was the most frequent side effect observed during treatment. PMID- 22050701 TI - Cigarette smoke exposure hinders long-term allograft survival by suppressing indoleamine 2, 3-dioxygenase expression. AB - Cigarette smoke causes cancer and increases the vulnerability of smokers to infections. Epidemiologic studies have shown that smoking is one of major risk factors for late allograft rejection. Despite statistical data that associate smoking with allograft rejection, no any study has been conducted to prove that cigarette smoke directly causes allograft rejection in a cause-effect manner. In particular, investigation into immunologic mechanisms underlying smoke-related allograft rejection is lacking. Here we found that second hand smoke (SHS) hindered long-term islet allograft survival induced by CD154 costimulatory blockade plus donor-specific splenocyte transfusion (DST), although it failed to alter acute islet allograft rejection. SHS did not directly interfere with vigorously alloreactive T-cell proliferation in vivo and in vitro. Neither naturally occurring nor induced CD4+CD25+ Treg cell numbers were significantly reduced by SHS. However, SHS suppressed mRNA and protein expression of indoleamine 2, 3-dioxygenase (IDO) and its activity upon transplantation while IDO overexpression in islet allografts restored their long-term survival induced by CD154 blockade. Therefore, SHS prevents long-term allograft survival by inhibiting IDO expression and activity. Thus, our study for the first time demonstrates that SHS shortens allograft survival in a cause-effect manner and unveils a novel immunologic mechanism underlying smoking-related allograft rejection. PMID- 22050702 TI - Functional microRNA screening using a comprehensive lentiviral human microRNA expression library. AB - BACKGROUND: MicroRNAs (miRNAs) are a class of small regulatory RNAs that target sequences in messenger RNAs (mRNAs) to inhibit their protein output. Dissecting the complexities of miRNA function continues to prove challenging as miRNAs are predicted to have thousands of targets, and mRNAs can be targeted by dozens of miRNAs. RESULTS: To systematically address biological function of miRNAs, we constructed and validated a lentiviral miRNA expression library containing 660 currently annotated and 422 candidate human miRNA precursors. The miRNAs are expressed from their native genomic backbone, ensuring physiological processing. The arrayed layout of the library renders it ideal for high-throughput screens, but also allows pooled screening and hit picking. We demonstrate its functionality in both short- and long-term assays, and are able to corroborate previously described results of well-studied miRNAs. CONCLUSIONS: With the miRNA expression library we provide a versatile tool for the systematic elucidation of miRNA function. PMID- 22050703 TI - Portrait of socio-economic inequality in childhood morbidity and mortality over time, Quebec, 1990-2005. AB - AIM: To determine the age and cause groups contributing to absolute and relative socio-economic inequalities in paediatric mortality, hospitalisation and tumour incidence over time. METHODS: Deaths (n= 9559), hospitalisations (n= 834,932) and incident tumours (n= 4555) were obtained for five age groupings (<1, 1-4, 5-9, 10 14, 15-19 years) and four periods (1990-1993, 1994-1997, 1998-2001, 2002-2005) for Quebec, Canada. Age- and cause-specific morbidity and mortality rates for males and females were calculated across socio-economic status decile based on a composite deprivation score for 89 urban communities. Absolute and relative measures of inequality were computed for each age and cause. RESULTS: Mortality and morbidity rates tended to decrease over time, as did absolute and relative socio-economic inequalities for most (but not all) causes and age groups, although precision was low. Socio-economic inequalities persisted in the last period and were greater on the absolute scale for mortality and hospitalisation in early childhood, and on the relative scale for mortality in adolescents. Four causes (respiratory, digestive, infectious, genito-urinary diseases) contributed to the majority of absolute inequality in hospitalisation (males 85%, females 98%). Inequalities were not pronounced for cause-specific mortality and not apparent for tumour incidence. CONCLUSIONS: Socio-economic inequalities in Quebec tended to narrow for most but not all outcomes. Absolute socio-economic inequalities persisted for children <10 years, and several causes were responsible for the majority of inequality in hospitalisation. Public health policies and prevention programs aiming to reduce socio-economic inequalities in paediatric health should account for trends that differ across age and cause of disease. PMID- 22050704 TI - For money or service?: a cross-sectional survey of preference for financial versus non-financial rural practice characteristics among Ghanaian medical students. AB - BACKGROUND: Health worker shortage and maldistribution are among the biggest threats to health systems in Africa. New medical graduates are prime targets for recruitment to deprived rural areas. However, little research has been done to determine the influence of workers' background and future plans on their preference for rural practice incentives and characteristics. The purpose of this study was to identify determinants of preference for rural job characteristics among fourth year medical students in Ghana. METHODS: We asked fourth-year Ghanaian medical students to rank the importance of rural practice attributes including salary, infrastructure, management style, and contract length in considering future jobs. We used bivariate and multivariate ordinal logistic regression to estimate the association between attribute valuation and students' socio-demographic background, educational experience, and future career plans. RESULTS: Of 310 eligible fourth year medical students, complete data was available for 302 students (97%). Students considering emigration ranked salary as more important than students not considering emigration, while students with rural living experience ranked salary as less important than those with no rural experience. Students willing to work in a rural area ranked infrastructure as more important than students who were unwilling, while female students ranked infrastructure as less important than male students. Students who were willing to work in a rural area ranked management style as a more important rural practice attribute than those who were unwilling to work in a rural area. Students studying in Kumasi ranked contract length as more important than those in Accra, while international students ranked contract length as less important than Ghanaian students. CONCLUSIONS: Interventions to improve rural practice conditions are likely to be more persuasive than salary incentives to Ghanaian medical students who are willing to work in rural environments a priori. Policy experiments should test the impact of these interventions on actual uptake by students upon graduation. PMID- 22050705 TI - Carbon nanotube active-matrix backplanes for conformal electronics and sensors. AB - In this paper, we report a promising approach for fabricating large-scale flexible and stretchable electronics using a semiconductor-enriched carbon nanotube solution. Uniform semiconducting nanotube networks with superb electrical properties (mobility of ~20 cm2 V(-1) s(-1) and ION/IOFF of ~10(4)) are obtained on polyimide substrates. The substrate is made stretchable by laser cutting a honeycomb mesh structure, which combined with nanotube-network transistors enables highly robust conformal electronic devices with minimal device-to-device stochastic variations. The utility of this device concept is demonstrated by fabricating an active-matrix backplane (12*8 pixels, physical size of 6*4 cm2) for pressure mapping using a pressure sensitive rubber as the sensor element. PMID- 22050706 TI - An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males. AB - BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD. METHODS: We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set. RESULTS: One SNP, rs17321050, in the transducin beta-like 1X-linked (TBL1X) gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (P value = 4.86 * 10-6) and joint analysis (P value = 4.53 * 10-6) in males. The SNP was also close to the replication threshold of 0.0025 in the discovery data set (P = 5.89 * 10-3) and passed the replication threshold in the validation data set (P = 2.56 * 10 4). Two other SNPs in the same gene in linkage disequilibrium with rs17321050 also showed significance close to the chromosome-wide threshold in the meta analysis. CONCLUSIONS: TBL1X is in the Wnt signaling pathway, which has previously been implicated as having a role in autism. Deletions in the Xp22.2 to Xp22.3 region containing TBL1X and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, based on meta-analysis, joint analysis and replication analysis, suggest that TBL1X may play a role in ASD risk. PMID- 22050708 TI - Chemical speciation of vanadium in particulate matter emitted from diesel vehicles and urban atmospheric aerosols. AB - We report on the development and application of an integrated set of analytical tools that enable accurate measurement of total, extractable, and, importantly, the oxidation state of vanadium in sub-milligram masses of environmental aerosols and solids. Through rigorous control of blanks, application of magnetic-sector ICPMS, and miniaturization of the extraction/separation methods we have substantially improved upon published quantification limits. The study focused on the application of these methods to particulate matter (PM) emissions from diesel vehicles, both in baseline configuration without after-treatment and also equipped with advanced PM and NO(x) emission controls. Particle size-resolved vanadium speciation data were obtained from dynamometer samples containing total vanadium pools of only 0.2-2 ng and provide some of the first measurements of the oxidation state of vanadium in diesel vehicle PM emissions. The emission rates and the measured fraction of V(V) in PM from diesel engines running without exhaust after-treatment were both low (2-3 ng/mile and 13-16%, respectively). The V(IV) species was measured as the dominant vanadium species in diesel PM emissions. A significantly greater fraction of V(V) (76%) was measured in PM from the engine fitted with a prototype vanadium-based selective catalytic reductors (V-SCR) retrofit. The emission rate of V(V) determined for the V-SCR equipped vehicle (103 ng/mile) was 40-fold greater than that from the baseline vehicle. A clear contrast between the PM size-distributions of V(V) and V(IV) emissions was apparent, with the V(V) distribution characterized by a major single mode in the ultrafine (<0.25 MUm) size range and the V(IV) size distribution either flat or with a small maxima in the accumulation mode (0.5-2 MUm). The V(V) content of the V-SCR PM (6.6 MUg/g) was 400-fold greater than that in PM from baseline (0.016 MUg/g) vehicles, and among the highest of all environmental samples examined. Synchrotron based V 1s XANES spectroscopy of vanadium-containing fine-particle PM from the V-SCR identified V(2)O(5) as the dominant vanadium species. PMID- 22050709 TI - Richter transformation: clonal identity does not indicate a linear disease progression. PMID- 22050707 TI - Modulation of microRNA 20b with resveratrol and longevinex is linked with their potent anti-angiogenic action in the ischaemic myocardium and synergestic effects of resveratrol and gamma-tocotrienol. AB - Resveratrol, a constituent of red wine, and gamma-tocotrienol, a constituent of palm oil are important for cardioprotection. Although microRNAs are known regulators for genes involved in cardiac remodelling, the regulatory pathway involving microRNA has not been studied so far. We explored the cardioprotection by resveratrol, longevinex and gamma-tocotrienol in ischaemia/reperfusion(I/R) model of rat and determined miRNA profile from isolated RNA. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches. Resveratrol and gamma-tocotrienol, either alone or in combination, modulated the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 75 miRNAs, some of them, such as miR-21 and miR-20b (anti-angiogenic) were previously implicated in cardiac remodelling. The target genes for the highest differentially expressed miRNA include genes of various molecular functions such as TGFbeta1-Smad3 signalling pathway, inflammation and their transcription factors, which may play key role in reducing I/R injury. Administration of antagomiR-20 attenuated I/R induced vascular endothelial growth factor and HIF1alpha level. All the interventions treated for 3 weeks lead to significant cardioprotection against ischaemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or gamma-tocotrienol. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R rat. Interestingly, resveratrol and gamma-tocotrienol resulted in synergestic action. PMID- 22050710 TI - A maxillary lateral incisor with four root canals. AB - AIM: To describe the successful non-surgical endodontic management of a permanent maxillary lateral incisor tooth with four root canals. SUMMARY: Aberrant morphology of root canals can occur in any tooth, including maxillary lateral incisors. In the presented case, clinical examination and radiographs clearly depicted the presence of four root canals in a right maxillary lateral incisor. The differential diagnosis included fusion, gemination, dens invaginatus or a combination of these. The report emphasises the need for attention during root canal treatment of maxillary lateral incisors. KEY LEARNING POINTS: * Clinicians should be aware of the variable root canal anatomy in maxillary lateral incisor teeth. * Careful examination of radiographs and the internal anatomy of teeth are essential prerequisites for successful root canal treatment. * Four root canals in maxillary lateral incisors is a possibility. PMID- 22050711 TI - Short communication: activating transcription factor 4 (ATF4) promotes HIV type 1 activation. AB - Activating transcription factor 4 (ATF4) is a central factor in the cellular response to multiple stresses, including altered metabolic conditions, anoxia and hypoxia, and redox stress. ATF4 is triggered by endoplasmic reticulum stress and consequent unfolded protein response. This report identifies for the first time ATF4 as a transcription factor upregulated by HIV-1 infection. Upregulation of ATF4 enhances HIV replication, by synergistic interactions with HIV Tat. Moreover, in specific cell lines ATF4 has a direct transactivating potential on the LTR, even in the absence of Tat. We also provide evidence that expression of ATF4 induces HIV reactivation in chronically infected cell lines. These results show for the first time that ATF4 induction might have an important role in HIV replication, and suggest that ATF4 might represent a convergent signaling molecule for different stressors important in regulating the HIV-1 cycle. PMID- 22050712 TI - Evaluation of topical nalbuphine or oral tramadol as analgesics for corneal pain in dogs: a pilot study. AB - OBJECTIVE: To evaluate the effectiveness of topical nalbuphine or oral tramadol in the treatment of corneal pain in dogs. ANIMALS STUDIED: Fourteen male Beagle dogs. PROCEDURES: Dogs were divided into three treatment groups and sedated with dexmedetomidine (5 MU/kg IV). A 4 mm corneal epithelial wound was created in the right eye (OD) of all dogs. Sedation was reversed with atipamazole IM. All dogs received pre/post ophthalmic examinations. Post operatively, Group NB (n = 5) received topical 1% preservative-free nalbuphine OD q8 h and an oral placebo PO q8 h. Group TR (n = 5) received tramadol (4 mg/kg) PO q8 h and topical sterile saline OD q8 h. Group CNTRL (n = 4) received topical sterile saline OD q8 h and an oral placebo q8 h. All dogs received topical 0.3% gentamicin OD TID until healed. Dogs were pain scored using a pain scoring system modified from the University of Melbourne pain scale at 0, 1, 2, 4, and 6 h, then every 6 h by observers masked to treatment, until corneal wounds were healed. Treatment failure was recorded if cumulative pain scores were above a minimum threshold of acceptable pain and rescue analgesia of morphine (1.0 mg/kg IM) was administered subsequently. RESULT: Four dogs in Group NB, one dog in Group TR, and two dogs in Group CNTRL required rescue analgesia. There was no significant difference in the incidence of treatment failure between groups (P = 0.184). Mean time to rescue was 9.16 h. All corneal wounds were healed by 84 h. CONCLUSIONS: The results of this study suggest tramadol rather than nalbuphine should be further investigated for the treatment of corneal pain. PMID- 22050713 TI - The spatial and temporal determinants of campylobacteriosis notifications in New Zealand, 2001-2007. AB - Despite recent improvements, New Zealand still has one of the highest per-capita incidence rates of campylobacteriosis in the world. To reduce the incidence, a thorough understanding of the epidemiology of infection is needed. This retrospective analysis of 36 000 notified human cases during a high-risk period between 2001 and 2007 explored the spatial and temporal determinants of Campylobacter notifications at a fine spatial scale in order to improve understanding of the complex epidemiology. Social deprivation was associated with a decreased risk of notification, whereas urban residence was associated with an increased risk. However, for young children rural residence was a risk factor. High dairy cattle density was associated with an increased risk of notification in two of the three regions investigated. Campylobacter notification patterns exhibit large temporal variations; however, few factors were associated with periods of increased risk, in particular temperature did not appear to drive the seasonality in campylobacteriosis. PMID- 22050714 TI - Relationship between humeral geometry and shoulder muscle power among suspensory, knuckle-walking, and digitigrade/palmigrade quadrupedal primates. AB - Shoulder morphology is functionally related to different patterns of locomotion in primates. To investigate this we performed a quantitative analysis of the relationship between cortical bone thickness (Cbt) of the muscle/tendon attachment site on the humerus and physiological cross-sectional area (PCSA) of the shoulder muscle in primates with different locomotory habits. The deltoid, subscapularis, supraspinatus, and infraspinatus were investigated. A chimpanzee, a gibbon, a baboon, two species of macaque, a lutong, a capuchin, and a squirrel monkey were included in the study. The total length of the humerus was measured and the values were converted into three-dimensional reconstructed data on a computer by computed tomography. The Cbt values were obtained from the volumes divided by the areas of the muscle/tendon attachment sites of the humerus by computer analysis. Muscle mass, muscle fascicle length, and muscle pennation angle were measured and PCSA was calculated using these parameters. A relatively high Cbt and small PCSA were characteristic of the gibbon. The gibbon's high Cbt suggests that passive tension in the muscle/tendon attachment site of suspensory primates (brachiators) may be greater than that of quadrupedal primates, whereas the relatively small PCSA indicates an association with a large amount of internal muscle fascia to endure the passive stress of brachiation. Although chimpanzees undertake some suspensory locomotion, the results for this species resemble those of the digitigrade/palmigrade quadrupedal primates rather than those of the suspensory primate. However, the deltoid and subscapularis in chimpanzee differ from those of the other primates and appear to be affected by the peculiar locomotion of knuckle-walking, i.e. the moment arm of forelimb in chimpanzees is relatively longer than that of digitigrade/palmigrade quadrupedal primates. Hence, a large PCSA in the deltoid and subscapularis may contribute to sustaining the body weight during locomotion. On the other hand, a thin cortical bone relative to a large PCSA was a feature of the cercopithecids, indicating that digitigrade/palmigrade quadrupedal locomotion produces less tension at the muscle/tendon attachment sites compared with that produced by brachiators. PMID- 22050715 TI - Molecular detection of Torque teno virus in different breeds of swine. AB - BACKGROUND: Torque teno virus (TTV), of the Anelloviridae family, Iotatorquevirus genus, is a non-enveloped, single-stranded, and negative sense DNA (ssDNA) virus infecting human and many domestic animals including swines. Very little information is known about the investigations of TTV prevalence in different swine breeds so far. METHODS: In this study, 208 serum samples collected from seven swine breeds (Rongchang pig, Chenghua pig, Zibet pig, Wild boar, Duroc, Landrace, Large Yorkshire) from two independent farms were detected to determine the prevalence of two swine TTV genogroups, TTV1 and TTV 2, by nested polymerase chain reaction methods, and to analyse prevalence difference among these breeds. RESULTS: The results showed that the prevalence of TTV in the seven breeds was 92%-100%. No significant difference (p > 0.05) in TTV infection was observed between different breeds. Interestingly, significantly higher prevalence for TTV1 in Rongchang boars (90%) and for TTV2 in Rongchang sows (95%) were detected, while co-infection rate (43.8%) was lower than other breeds. Sequence analysis showed that the homology of TTV1 and TTV2 were over 90.9% and 86.4% in these breeds, respectively. CONCLUSIONS: The results indicated that TTV was widely distributed in the seven swine breeds. The prevalence of both TTV genogroups associated with swine breeds and genders. This study also respented the first description of swine TTV prevalence in different swine breeds. It was vitally necessary to further study swine TTV pathogenicity. PMID- 22050716 TI - A portable, contact animal fundus imaging system based on Rol's GRIN lenses. AB - OBJECTIVE: To demonstrate a cost-effective, portable, and simple-to-use fundus imaging system for laboratory animals. ANIMALS STUDIED: Albino rats, pigmented mice, albino guinea pigs, and New Zealand white rabbits. PROCEDURE: A contact fundus imaging system was designed and constructed using standard optical and mechanical components: a digital camera, an otoscope, a fiber optic light source, and standard optical lenses and mounts. Digital fundus video and photography of two albino rats, two pigmented mice, two New Zealand white rabbits, and two albino guinea pigs were obtained. For all animals examined, pupils were dilated and local anesthetic was administered. RESULTS: Digital images of the fundus were obtained in all animals. Contrast of retinal vasculature and overall image quality varied from one species to another, as the axial length, ocular optics, and retinal reflectance varied significantly across species. Light intensity and focus were optimized via the light source and lens focusing mount to produce high quality images for each animal. CONCLUSIONS: The portable, cost-effective contact fundus imaging system was easy to use for fundus examination of laboratory animals. PMID- 22050717 TI - What's Up, Doc? PMID- 22050718 TI - Academy of Operative Dentistry Award of Excellence. PMID- 22050719 TI - Erratum. PMID- 22050722 TI - Comparing Enterovirus 71 with Coxsackievirus A16 by analyzing nucleotide sequences and antigenicity of recombinant proteins of VP1s and VP4s. AB - BACKGROUND: Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are two major etiological agents of Hand, Foot and Mouth Disease (HFMD). EV71 is associated with severe cases but not CA16. The mechanisms contributed to the different pathogenesis of these two viruses are unknown. VP1 and VP4 are two major structural proteins of these viruses, and should be paid close attention to. RESULTS: The sequences of vp1s from 14 EV71 and 14 CA16, and vp4s from 10 EV71 and 1 CA16 isolated in this study during 2007 to 2009 HFMD seasons were analyzed together with the corresponding sequences available in GenBank using DNAStar and MEGA 4.0. Phylogenetic analysis of complete vp1s or vp4s showed that EV71 isolated in Beijing belonged to C4 and CA16 belonged to lineage B2 (lineage C). VP1s and VP4s from 4 strains of viruses expressed in E. coli BL21 cells were used to detect IgM and IgG in human sera by Western Blot. The detection of IgM against VP1s of EV71 and CA16 showed consistent results with current infection, while none of the sera were positive against VP4s of EV71 and CA16. There was significant difference in the positive rates between EV71 VP1 and CA16 VP1 (chi(2) = 5.02, P < 0.05) as well as EV71 VP4 and CA16 VP4 (chi(2) = 15.30, P < 0.01) in the detection of IgG against recombinant proteins with same batch of serum samples. The sera-positive rate of IgG against VP1 was higher than that against VP4 for both EV71 (chi(2) = 26.47, P < 0.01) and CA16 (chi(2) = 16.78, P < 0.01), which might be because of different positions of VP1 and VP4 in the capsid of the viruses. CONCLUSIONS: EV71 and CA16 were highly diverse in the nucleotide sequences of vp1s and vp4s. The sera positive rates of VP1 and VP4 of EV71 were lower than those of CA16 respectively, which suggested a less exposure rate to EV71 than CA16 in Beijing population. Human serum antibodies detected by Western blot using VP1s and VP4s as antigen indicated that the immunological reaction to VP1 and VP4 of both EV71 and CA16 was different. PMID- 22050723 TI - Conjunctival dacryops in two golden retrievers. AB - Two 5-month-old golden retriever dogs were referred for the evaluation of a mass arising from the left ventrolateral conjunctiva of the lower eyelid. The masses were externally located, deemed to be cystic in nature, and were surgically removed, and in one case, 0.15 mL of clear fluid was collected. Cytological examination of the aspirated fluid revealed proteinaceous, basophilic amorphous material, and few epithelial cells with foamy cytoplasm and small nuclei. No micro-organisms were detected. Histological examination of the cysts showed a wall composed of single to double cell layers. The cells were cuboidal to flattened, nonciliated, lined with mild submucosal connective tissues and slight inflammation composed of lymphocytes, plasma cells, and rare macrophages. In some areas, lobules of acinar glandular tissue were observed. To the authors' knowledge, this is the first case report of conjunctival dacryops in dogs. The complete surgical removal of the cysts was curative in both cases. PMID- 22050724 TI - Transplant accommodation--are the lessons learned from xenotransplantation pertinent for clinical allotransplantation? AB - "Accommodation" refers to a vascularized transplant that has acquired resistance to antibody-mediated rejection (AMR). The term was coined in 1990, but the phenomenon was first described after clinical ABO-incompatible (ABOi) renal transplantation in the 1980s and is recognized as a common outcome in this context today. Because of the absence, until recently of reliable animal models of allograft accommodation, it has been studied extensively by investigators in the xenotransplantation field. With recent advances in the ability to recognize and diagnose AMR in human organs, the growth of desensitization programmes for transplantation into sensitized recipients and the availability of therapies that have the potential to promote accommodation, it is timely to review the literature in this area, identifying lessons that may inform preclinical and clinical studies in the future. PMID- 22050725 TI - Synthesis of an azide-bearing N-mustard analogue of S-adenosyl-L-methionine. AB - The synthesis of an azide-bearing N-mustard S-adenosyl-L-methionine (SAM) analogue, 8-azido-5'-(diaminobutyric acid)-N-iodoethyl-5'-deoxyadenosine, has been accomplished in 10 steps from commercially available 2',3'-isopropylidene adenosine. Critical to this success was executing C8 azidation prior to derivatizing the 5'-position of the ribose sugar and the late stage alkylation of the 5' amino group with bromoethanol, which was necessitated by the reactivity of the aryl azide moiety. The azide-bearing N-mustard is envisioned as a useful biochemical tool by which to probe DNA and protein methylation patterns. PMID- 22050726 TI - Misconceived causal explanations for emergent processes. AB - Studies exploring how students learn and understand science processes such as diffusion and natural selection typically find that students provide misconceived explanations of how the patterns of such processes arise (such as why giraffes' necks get longer over generations, or how ink dropped into water appears to "flow"). Instead of explaining the patterns of these processes as emerging from the collective interactions of all the agents (e.g., both the water and the ink molecules), students often explain the pattern as being caused by controlling agents with intentional goals, as well as express a variety of many other misconceived notions. In this article, we provide a hypothesis for what constitutes a misconceived explanation; why misconceived explanations are so prevalent, robust, and resistant to instruction; and offer one approach of how they may be overcome. In particular, we hypothesize that students misunderstand many science processes because they rely on a generalized version of narrative schemas and scripts (referred to here as a Direct-causal Schema) to interpret them. For science processes that are sequential and stage-like, such as cycles of moon, circulation of blood, stages of mitosis, and photosynthesis, a Direct causal Schema is adequate for correct understanding. However, for science processes that are non-sequential (or emergent), such as diffusion, natural selection, osmosis, and heat flow, using a Direct Schema to understand these processes will lead to robust misconceptions. Instead, a different type of general schema may be required to interpret non-sequential processes, which we refer to as an Emergent-causal Schema. We propose that students lack this Emergent Schema and teaching it to them may help them learn and understand emergent kinds of science processes such as diffusion. Our study found that directly teaching students this Emergent Schema led to increased learning of the process of diffusion. This article presents a fine-grained characterization of each type of Schema, our instructional intervention, the successes we have achieved, and the lessons we have learned. PMID- 22050727 TI - Editorial comment to extended versus limited lymph node dissection in radical cystectomy: impact on recurrence pattern and survival. PMID- 22050729 TI - Infant gender, shared sleeping and sudden death. AB - AIM: To determine whether there is a gender imbalance in infant deaths in shared sleeping compared to solitary sleeping situations. METHODS: Examination of autopsy reports of 133 infants aged between 7 and 364 days autopsied over a 19 year period from January 1991 to December 2009 was undertaken where death had either been attributed to SIDS, or had been classified as undetermined or unascertained. Cases were divided into two groups of solitary sleepers and shared sleepers, and the ratio of male to female cases was compared. RESULTS: Ninety five solitary sleepers were aged from 1 to 11 months (average 4.1 months) and consisted of 63 males (age range 1 to 11 months) and 32 females (age range 1 to 10 months). The 38 shared sleepers were aged from 1 week to 12 months (average 2.6 months) and consisted of 17 males (age range 2 weeks to 5 months) and 21 females (age range 1 week to 10 months). The male to female ratio in the solitary sleepers was approximately 2:1 and in the shared sleepers was 0.8:1, a statistically significant difference (p = 0.02). CONCLUSION: The lack of a male predominance typical of SIDS cases in infants who were sleeping with others, compared to those who were sleeping alone, suggests that these situations may be different. It is possible, therefore, that different lethal mechanisms may be involved in some shared sleeping situations. PMID- 22050728 TI - Effect of genetic and environmental influences on cardiometabolic risk factors: a twin study. AB - BACKGROUND: Both genetic and environmental factors play a role in the pathogenesis of type 2 diabetes and cardiovascular diseases. The magnitude of genetic and environmental influences may vary in different populations and can be investigated by twin studies. METHODS: In this cross-sectional study, 101 (63 monozygotic and 38 dizygotic) adult twin pairs (n = 202; mean age: 44.3 +/- 15.8 years) were investigated. Past medical history was recorded and physical examination was performed. Fasting venous blood samples were taken for measuring laboratory parameters. For assessing heritability of 14 cardiovascular risk factors, the structural equation (A-C-E) model was used. RESULTS: The following risk factors were highly (> 70.0%) or moderately (50.0 - 69.0%) heritable: weight (88.1%), waist circumference (71.0%), systolic blood pressure (57.1%), diastolic blood pressure (57.7%), serum creatinine (64.1%), fibrinogen (59.9%), and serum C reactive protein (51.9%). On the other hand, shared and unique environmental influences had the highest proportion of total phenotypic variance in serum total cholesterol (46.8% and 53.2%), serum HDL-cholesterol (58.1% and 14.9%), triglycerides (0.0% and 55.9%), fasting blood glucose (57.1% and 42.9%), fasting insulin (45.4% and 54.5%), serum uric acid (46.0% and 31.3%), and serum homocysteine (71.8% and 28.2%, respectively). CONCLUSION: Some cardiometabolic risk factors have strong heritability while others are substantially influenced by environmental factors. Understanding the special heritability characteristics of a particular risk factor can substantiate further investigations, especially in molecular genetics. Moreover, identifying genetic and environmental contribution to certain cardiometabolic risk factors can help in designing prevention and treatment strategies in the population investigated. PMID- 22050730 TI - Fully printed separated carbon nanotube thin film transistor circuits and its application in organic light emitting diode control. AB - The advantages of printed electronics and semiconducting single-walled carbon nanotubes (SWCNTs) are combined for the first time for display electronics. Conductive silver ink and 98% semiconductive SWCNT solutions are used to print back-gated thin film transistors with high mobility, high on/off ratio, and high current carrying capacity. In addition, with printed polyethylenimine with LiClO4 as the gating material, fully printed top-gated devices have been made to work as excellent current switches for organic light emitting diodes (OLEDs). An OLED driving circuit composed of two top-gated fully printed transistors has been fabricated, and the successful control over external OLED is demonstrated. Our work demonstrates the significant potential of using printed carbon nanotube electronics for display backplane applications. PMID- 22050731 TI - Composite effects of gene determinants on the translation speed and density of ribosomes. AB - BACKGROUND: Translation is a central process of life, and its regulation is crucial for cell growth. In this article, focusing on two model organisms, Escherichia coli and Saccharomyces cerevisiae, we study how three major local features of a gene's coding sequence (its adaptation to the tRNA pool, its amino acid charge, and its mRNA folding energy) affect its translation elongation. RESULTS: We find that each of these three different features has a non-negligible distinct correlation with the speed of translation elongation. In addition, each of these features might contribute independently to slowing down ribosomal speed at the beginning of genes, which was suggested in previous studies to improve ribosomal allocation and the cost of translation, and to decrease ribosomal jamming. Remarkably, a model of ribosomal translation based on these three basic features highly correlated with the genomic profile of ribosomal density. The robustness to transcription errors in terms of the values of these features is higher at the beginnings of genes, suggesting that this region is important for translation. CONCLUSIONS: The reported results support the conjecture that translation elongation speed is affected by the three coding sequence determinants mentioned above, and not only by adaptation to the tRNA pool; thus, evolution shapes all these determinants along the coding sequences and across genes to improve the organism's translation efficiency. PMID- 22050732 TI - Viral interference with innate immunity by preventing NF-kappaB activity. AB - Viruses are the most abundant and diverse pathogens challenging the host immune system, and as such are a severe threat to human health. To this end, viruses have evolved multiple strategies to evade and subvert the host immune response. Host-pathogen interactions are usually initiated via recognition of pathogen associated molecular patterns (PAMPs) by host sensors known as pattern recognition receptors (PRRs), which include, Toll-like receptors (TLRs), RIG-I like receptors (RLRs), NOD-like receptors (NLRs) and DNA receptors. Effective sensing of PAMPs rapidly triggers host immune responses, via activation of complex signalling pathways that culminates in the induction of inflammatory responses and the eradication of pathogens. Activation of the nuclear factor kappaB (NF-kappaB) transcription pathway is crucial for the immediate early step of immune activation. This review discusses the recent evidence describing a variety of viral effectors that have been shown to prevent NF-kappaB signalling. Most of these viral effectors can be broadly classified into three categories based on the site of inhibition within the NF-kappaB pathway, that is, at the (i) TLRs, (ii) IKK complex or (iii) the transcriptional level. PMID- 22050734 TI - Short communication: UGT1A1*28 variant allele is a predictor of severe hyperbilirubinemia in HIV-infected patients on HAART in southern Brazil. AB - Highly active antiretroviral therapy (HAART) has increased the survival of HIV infected patients. However, adverse effects play a major role in adherence to HAART. Some protease inhibitors (mainly atazanavir and indinavir) act as inhibitors of uridine diphosphate-glucuronosyltransferase (UGT1A1), the enzyme responsible for hepatic conjugation of bilirubin. Variations in the promoter region of the UGT1A1 gene (UGT1A1*28, rs8175347) can influence bilirubin plasma levels, modulating the susceptibility to hyperbilirubinemia. Aiming to analyze the association between UGT1A1*28 allele and hyperbilirubinemia in individuals exposed to HAART, we evaluated 375 HIV-positive individuals on antiretroviral therapy. Individuals carrying the UGT1A1*28 allele had a higher risk of developing severe hyperbilirubinemia [prevalence ratio (PR)=2.43, 95% confidence interval (CI) 1.08-5.45, p=0.032] as well as atazanavir users (PR=7.72, 95% CI=3.14-18.98, p<0.001). This is the first description of such an association in Brazilian HIV patients, which shows that in African-American and Euroamerican HAART users, the UGT1A1*28 allele also predisposes to severe hyperbilirubinemia, especially in those exposed to atazanavir. PMID- 22050733 TI - The role of dorsal root ganglia activation and brain-derived neurotrophic factor in multiple sclerosis. AB - Multiple sclerosis (MS) is characterized by focal destruction of the white matter of the brain and spinal cord. The exact mechanisms underlying the pathophysiology of the disease are unknown. Many studies have shown that MS is predominantly an autoimmune disease with an inflammatory phase followed by a demyelinating phase. Recent studies alongside current treatment strategies, including glatiramer acetate, have revealed a potential role for brain-derived neurotrophic factor (BDNF) in MS. However, the exact role of BDNF is not fully understood. We used the experimental autoimmune encephalomyelitis (EAE) model of MS in adolescent female Lewis rats to identify the role of BDNF in disease progression. Dorsal root ganglia (DRG) and spinal cords were harvested for protein and gene expression analysis every 3 days post-disease induction (pdi) up to 15 days. We show significant increases in BDNF protein and gene expression in the DRG of EAE animals at 12 dpi, which correlates with peak neurological disability. BDNF protein expression in the spinal cord was significantly increased at 12 dpi, and maintained at 15 dpi. However, there was no significant change in mRNA levels. We show evidence for the anterograde transport of BDNF protein from the DRG to the dorsal horn of the spinal cord via the dorsal roots. Increased levels of BDNF within the DRG and spinal cord in EAE may facilitate myelin repair and neuroprotection in the CNS. The anterograde transport of DRG-derived BDNF to the spinal cord may have potential implications in facilitating central myelin repair and neuroprotection. PMID- 22050738 TI - Operative Dentistry Home Page. PMID- 22050735 TI - Comparison of the pig and feline models for full thickness corneal transplantation. AB - PURPOSE: The goal of this study was to report on the advantages and limitations of the pig and feline models for experimental in vivo corneal transplantation. METHODS: Ten healthy domestic pigs and ten healthy cats were used. Full thickness penetrating keratoplasty was performed using autologous (eight cases), allogeneic (seven cases) or human xenogeneic (three cases) tissue. In two other cases, the inflammatory response to partial thickness trephination (without transplantation) was evaluated. Eyes were assessed daily before and after surgery by slit-lamp, pachymetry, and tonometry. A transparency score ranging from 0 (opaque graft) to 4 (clear graft) was used, based on the slit-lamp examination. Optical coherence tomography, histology, and electron microscopy were performed postmortem. RESULTS: In the pig, the mean (+/-SD) transparency score for the eight full thickness grafts was 0.88 +/- 0.99, ranging from 0 to 3. In the feline model, the mean transparency score for the seven uncomplicated grafts was 3.93 +/- 0.19, ranging from 3.5 to 4. Both negative controls without endothelium remained opaque at all time. Intraoperative tendency for iris incarceration into the wound, rapid corneal swelling, suture cheese wiring, and postoperative intraocular inflammation were the main factors jeopardizing the functional success of the corneal transplant in the pig model. CONCLUSION: Suboptimal functional results were obtained after full thickness corneal transplantation in the pig model, while in the feline model, the same protocol yielded uneventful surgeries and clear transplants, with functional results similar to those achieved in human subjects. PMID- 22050739 TI - Corporate Sponsorship. PMID- 22050740 TI - The HOX genes network in uro-genital cancers: mechanisms and potential therapeutic implications. AB - Genito-urinary malignancies (prostate, bladder, renal and testicular cancers) rank high among human tumors with an incidence that varies with age and organ involvement. Prostate cancer is the most commonly detected male cancer followed by bladder and kidney cancers, less frequent in women. Testicular cancer, although rare, is the most frequent cancer in males under 35. The majority of oncogenic and tumor suppressor signaling pathways involved with urogenital cancers converge on sets of transcription factors that ultimately control gene expression resulting in tumor formation and metastatic progression. The activity of these transcription factors is modulated by multiple mechanisms spanning from transcriptional regulation, deregulation of the splicing, maturation, export and location of mRNAs, protein synthesis and post-translational modifications. The recent involvement of the epigenitic mechanisms in the generation and the evolution of cancer has produced a great deal of interest. This is related to the possibility that revealing these mechanisms able to regulate the cell memory program (the gene systems polycomb, trithorax and HOX) may generate important biological and therapeutic achievements. The HOX gene network is the only physically and functionally identifiable transcription factor network located in the human genome controlling crucial cellular processes. Here we describe the implication of the HOX genes in the urogenital embryonic development and cancers. We further highlight the mechanisms uncovered along these processes and involving the HOX genes. Finally, we foresee the specific targeting of HOX genes and in general the cell memory gene program in the therapeutic setting of urogenital malignancies due to their upstream location in these stepwise cell processes and their early deregulation in cancer evolution. PMID- 22050741 TI - Aliphatic and aromatic oxidations, epoxidation and S-oxidation of prodrugs that yield active drug metabolites. AB - About one hundred and fifty of the several thousands of drugs on the market are known to have active metabolites. Medicinal chemistry of the parent drugs as well as that of the metabolites are very important both in medical practice and drug research. The efficacy of a drug will depend on a number of properties including, pharmacokinetic behavior, absorption, tissue distribution, pharmacological potency, toxicity and tissue-specificity. The production and release of active metabolites are important because active drug metabolites may influence the clinical outcome of a drug by increasing the gross level of pharmacologically active compounds (drug + active metabolite) and/or essentially increasing the duration of drug effect, when t(1/2) of active metabolite is much longer than that of the parent drug. Furthermore, certain drug metabolizing enzymes can either be inhibited or induced by other drugs and a variety of food and environmental factors. A careful control of the clinical effects of any drug with active metabolites is important especially in the treatment of the elderly population where the administration of several drugs is not unusual.This review provides a detailed description of the medicinal chemistry of drugs yielding active metabolites after undergoing transformation via aliphatic and aromatic oxidations, epoxidation and S-oxidation. Their respective pharmacologically active metabolites, metabolizing enzymes and changes in lipophilicity are also summarized. The most recent analytical methods used for the reliable quantification of both the parent drugs and their metabolites are also included. PMID- 22050742 TI - 1,4-Dihydropyridine scaffold in medicinal chemistry, the story so far and perspectives (part 1): action in ion channels and GPCRs. AB - Since the pioneering studies of Fleckenstein and co-workers, L-Type Calcium Channel (LTCC) blockers have attracted large interest due to their effectiveness in treating several cardiovascular diseases. Medicinal chemists achieved high potency and tissue selectivity by decorating the 1-4-DHP nucleus, the most studied scaffold among LTCC blockers. Nowadays it is clear that the 1,4-DHP nucleus is a privileged scaffold since, when appropriately substituted, it can selectively modulate diverse receptors, channels and enzymes. Therefore, the 1,4 DHP scaffold could be used to treat various diseases by a single-ligand multi target approach. In this review, we describe the structure-activity relationships of 1,4-DHPs at ion channels, G-protein coupled receptors, and outline the potential for future therapeutic applications. PMID- 22050743 TI - Alkaloids and flavonoids as alpha(1)-adrenergic receptor antagonists. AB - Since the subtypes of alpha(1)-adrenergic receptor have been thoroughly determined, to date medicinal chemists raise their deliberation on how to conceive selective alpha(1)-adrenergic receptor antagonist with the minimal side effects. It needs to be well recognized that natural products can exist as a significant source of drug leads, thus portraying a consequential capacity in drug design and development. The current review article would like to present a comprehensive survey on natural products, mainly including alkaloids and flavonoids, which exhibit alpha(1)-adrenergic receptor antagonistic activities. PMID- 22050744 TI - Classical neurotransmitters and neuropeptides involved in generalized epilepsy: a focus on antiepileptic drugs. AB - We describe the alterations of classical neurotransmitters and neuropeptides in generalized epilepsy. A neuronal network in this disease is developed. Gamma aminobutyric acid (GABA) hypoactivity induces dopamine hyperactivity because dopaminergic neurons are affected by the inhibitory influence of the GABAergic system through GABA(A) receptors. Glutamate hyperactivity is exerted via presynaptic N-methyl-D-aspartate (NMDA) receptors, which strongly inhibit serotoninergic neurons, and via postsynaptic ionotropic glutaminergic receptors, which can induce epileptic seizures. A collection of specific subreceptors of classical neurotransmitters and neuropeptides involved in epileptogenesis is reported. The question arises whether agonists/antagonists of neuropeptides (neuropeptide Y, galanin...) could have additional antiepileptic properties. The effect of conventional and newer antiepileptic drugs interfering with these subreceptors is discussed on the basis of the neuronal network suggested. From these data, it is concluded that new antiepileptic drugs interfering with other specific subreceptors (GABA(B) antagonists, metabotropic glutaminergic receptors subtype 5 (mGlu5R) antagonists, mGlu2/3R agonists, 5-serotonin (5-HT(7)) agonists) could further stabilize the neuronal network in generalized epilepsy. PMID- 22050745 TI - Multi-target-directed ligands in Alzheimer's disease treatment. AB - Among the various drug discovery methods, a very promising modern approach consists in designing multi-target-directed ligands (MTDLs). This methodology has been specifically developed for treatment of disorders with complex pathological mechanisms. One such disorder is Alzheimer's disease (AD), currently the most common multifactorial neurodegenerative disease. AD is related to increased levels of the amyloid beta peptide (Abeta) and the hyperphosphorylated tau protein, along with loss of neurons and synapses. Moreover, there is some evidence pointing to the role of oxidative stress, metal ion deregulation, inflammation and cell cycle regulatory failure in its pathogenesis. There are many attractive targets for the development of anti-AD drugs, and the multi factor nature of this disease calls for multi-target-directed compounds which can be beneficial for AD treatment. This review presents the discovery of dualand multi-acting anti-AD drug candidates, focusing on the novel design strategy and the compounds it yields - particularly hybrids obtained by linking structurally active moieties interacting with different targets. The first group of compounds includes cholinesterase inhibitors acting as dual binding site inhibitors and/or inhibitors with additional properties. These compounds are characterized by increased potency against acetylcholinesterase (AChE) and Abeta plaque formation with additional properties such as antioxidant activity, neuroprotective, and metal-complexing property, voltage-dependent calcium channel antagonistic activity, inhibitory activity against glutamate-induced excitotoxicity, histamine H(3) receptor antagonism, cannabinoid CB(1) receptor antagonism and beta secretase (BACE1) inhibition. A novel class of compounds represents the combination of dual BACE1 inhibitors with metal chelators, and dual modulators of gamma-secretase with peroxisome proliferator-ativated receptor gamma (PPARgamma). We have reviewed the latest reports (2008-2011) presenting new multi-target directed compounds in Alzheimer's disease treatment. PMID- 22050746 TI - Endocrine orchestration of cardiovascular, gastrointestinal and hypothalamic control. AB - The richly structured neuroendocrine control of the heart in health and disease requires, in addition to the autonomic nervous outflow, the essential contribute of various and often interacting humoral peptides (e.g. natriuretic peptides, Chromogranin-A-derived fragments, etc). In many cases, these molecules also influence the activity of other organ systems, including the gastrointestinal apparatus, in which they control mucosal function as well as motility and secretion. Interestingly, by acting centrally, some of these peptides also regulate satiety and appetite, thus forming an interesting link between cardiac and gastrointestinal function, and the feeding pattern. Prolonged inhibition and/or activation of these peptide pathways frequently results in severe and long lasting dysfunctions, including cardiovascular diseases associated to alimentary disorders (e.g. obesity). Notably, their multifarious actions and mutual interactions make them excellent candidates for long-term resetting of both cardiac, gastrointestinal and nutrition homeostasis. Here we will provide only few examples taken from the quickly evolving scenario, with the purpose to provide indications concerning the complex circuits generated by multilevel signalling peptides, which contributes to orchestrate the association between cardiovascular, gastrointestinal and alimentary functions. This will highlight not only the complexity of the cardiovascular and GI regulatory networks, but also aspects of integration between feeding stimulating peptides and the other neuroendocrine systems affecting the heart and the GI tract. PMID- 22050747 TI - Fatty liver and ischemia/reperfusion: are there drugs able to mitigate injury? AB - Fatty livers are more prone to damage caused by ischemia/reperfusion (I/R). Impaired microcirculation, Kupffer cell dysfunction, increased adhesion of leukocytes, impaired mitochondrial function and ATP depletion are probable causes for fatty liver susceptibility. Therefore, hepatic steatosis is a major risk factor for liver surgery and success of transplantation of fatty donor organs. The mechanisms involved in I/R injury are complex and there is no general consensus regarding the sources of ROS generation, nitric oxide (NO) action, the role of tumor necrosis factor-alpha (TNF-alpha), and transcription factors, such as nuclear factor kappa B (NFkappaB). Impairment of mitochondrial function is one of the most important alterations that occur in I/R injury, resulting in the alteration of energy metabolism. Ischemic preconditioning (IPC) and post conditioning (IPost) are adaptive mechanisms against I/R insults that induce intracellular protective responses associated with the preservation of mitochondrial function.There are several pharmacological drugs and natural derivatives presenting metabolic and/or antioxidant effects that can directly or indirectly protect the liver against I/R injury. While the precise targets and mechanisms are still not totally understood, the mitochondrion presents itself as a major player on mediating these protective events. As so, compounds that are able to improve mitochondrial function and hepatic energetic balance might prove viable candidates when developing new pharmacological approaches that can minimize injury to steatotic livers subjected to I/R events. PMID- 22050748 TI - Advances on aptamers targeting Plasmodium and trypanosomatids. AB - Aptamers are single-stranded oligonucleotides (ssDNA or RNA) selected from combinatorial libraries by an in vitro process and possess a specific three dimensional structure depending on its sequence. These molecules are able to recognize and, eventually, alter the activity of their targets by binding directly in a similar way to antibodies. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against Plasmodium and trypanosomatid proteins associated with parasitic diseases which affect hundreds of millions people. One approach tries to block the interaction between the parasite and the host using aptamers targeting host-cell matrix receptors. A second strategy consists in attack the parasite intracellularly targeting heme group or interfering in the intracellular RNA transport. In another strategy, aptamers targeting invariant polypeptides could be used as a specific drug delivery system into the parasite. Finally, aptamers addressed to re-direct the immune response of the infected host are being studied. Other potential use of the aptamers is as biorecognition element in diagnostic systems for parasitic diseases. In this paper, we briefly review how aptamers against Plasmodium and trypanosomatids are discovered, with a focus on recent advances that improve the aptamers properties as a real tool for parasite fighting. PMID- 22050749 TI - Recent advance in aminopeptidase N (APN/CD13) inhibitor research. AB - APN is an important zinc dependent metallo-exopeptidase, which can degrade the extracellular matrix, and plays an important role in tumor invasion, metastasis and angiogenesis. it has been considered as a suitable target for anti-cancer drug design. Recently, research of structure-based APN inhibitors is becoming an interesting field, and many APN inhibitors have been reported. Here we review a series of APN inhibitors and the recent progress in this field. PMID- 22050750 TI - The role of antiangiogenetic agents in the treatment of breast cancer. AB - Angiogenesis is known to be essential for the development and progression of cancer. Vascular endothelial growth factor (VEGF) is a critical mediator in tumor angiogenesis for many solid malignancies, including breast cancer. Increased levels of VEGF have been associated with poor clinical outcomes, including reduced survival. VEGF has become an attractive target for cancer therapy in view of its pivotal role in angiogenesis. The primary approaches for inhibiting angiogenesis have focused on inhibiting the activity of VEGF, either by targeting the VEGF ligand itself with monoclonal antibodies (mAbs) or by interfering with the signaling events downstream of VEGF through the use of tyrosine kinase inhibitors (TKIs). Bevacizumab is a recombinant, humanized monoclonal IgG1, anti VEGF antibody that has demonstrated significant clinical benefit in several solid tumors. Bevacizumab has been approved for use in combination with paclitaxel for the first line treatment of patients with metastatic breast cancer (MBC) based on the results of the randomized phase III E2100 trial in which it improves response rate and time to progress when administered with weekly paclitaxel until disease progression. Several trials to define the role of bevacizumab in different setting of disease and in combination with different chemotherapy regimens and targeted therapy in breast cancer patients are ongoing. Other small molecule inhibitors of VEGF tyrosine kinase activity (TKIs) such as sunitinib, vandetanib and sorafenib are being tested in MBC. This review will focus on bevacizumab and on the developements of the main antiangiogenic agents in the treatment of breast cancer. PMID- 22050751 TI - New prognostic markers and potential therapeutic targets in human testicular germ cell tumors. AB - Although testicular germ cell tumors (TGCTs) are relatively uncommon, they are particularly important as they tend to affect children and young men, representing the most common tumor in male aged from 20 to 40 years, and the incidence has been increasing over the last decades. TGCTs are a heterogeneous group of tumors, with specific peculiarities reflecting on epidemiologic distribution and clinic-pathological features. Seminomas are highly sensitive to both radiation and chemotherapy, with a good prognosis, non- seminomas are sensitive to platinum-based combination chemotherapy and are less susceptible to radiation, with the exception of teratomas. However, up to 30% of patients diagnosed with metastatic nonseminomas do not achieve a durable remission, and in metastatic teratomas cisplatin-based treatment resistance has been observed. The different therapeutic outcome might be explained by inherent properties of the cells from which testicular neoplasia originate. The unique treatment sensitivity of TGCTs is unexplained so far, but it is likely to be related to intrinsic molecular characteristics of the PGCs/gonocytes, from which these tumours originate. In the last years novel markers, including OCT3/4, SOX2, SOX17, HMGA1, HMGA2, PATZ1, GPR30, Aurora B, and others has given further advantages to discriminate between histological subgroups. In addition, therapeutic approaches for the treatment of TGCTs have been proposed: humanized antibodies against receptors/surface molecules on cancer cells, inhibitors of serine-threonine, and tyrosine kinases, angiogenesis inhibitors, and others. In same cases the clinical trials have confirmed the efficacy of these approaches. The review will focus on the molecular alteration identified in post-puberal TGCTs and on novel targeted antineoplastic strategies that could contribute to the cure of chemotherapy resistant TGCTs. PMID- 22050752 TI - Insight to physiology and pathology of zinc(II) ions and their actions in breast and prostate carcinoma. AB - Zinc(II) ions contribute to a number of biological processes e.g. DNA synthesis, gene expression, enzymatic catalysis, neurotransmission, and apoptosis. Zinc(II) dysregulation, deficiency and over-supply are connected with various diseases, particularly cancer. 98 % of human body zinc(II) is localized in the intracellular compartment, where zinc(II) is bound with low affinity to metallothionein (MT). Zinc transporters ZIP and ZnT maintain transmembrane transport from/to cells or organelles. Imbalance of their regulation is described in cancers, particularly prostate (down-regulated zinc transporters ZIP1, 2, 3 and ZnT-2) and breast, notably its high-risk variant (up-regulated ZIP6, 7, 10). As a result, intracellular and even blood plasma zinc(II) levels are altered. MT protects cells against oxidative stress, because it cooperates with reduced glutathione (GSH). Recent studies indicate elevated serum level of MT in a number of malignancies, among others in breast, and prostate. MT together with zinc(II) affect apoptosis and proliferation, thus together with its antioxidative effects it may affect cancer. To date, only little is known about the influence of zinc(II) and MT on cancer, while these compounds may play an important role in pathogenesis. This review concludes current data regarding the impact of zinc(II) on the pathogenesis of breast and prostate cancers with potential outlines of new, targeted therapy and prevention. Moreover, blood plasma zinc(II) and MT levels and dietary zinc(II) intake are discussed in relation to breast and prostate cancer risk. PMID- 22050753 TI - Macrocyclic proteasome inhibitors. AB - Proteasome inhibitors have proven to be effective anticancer agents. Despite the success of the first on the market proteasome inhibitor bortezomib in chemotherapy, alternative clinically useful proteasome inhibitors are still urgently needed as bortezomib therapy causes severe side effects and is limited by arising drug resistance. Experience from previous proteasome inhibitor studies has thereby demonstrated that the identification of proteasome inhibitor structures with suitable pharmacological properties is a key factor for a successful development of clinically useful proteasome inhibitors. Macrocycles often show distinct and in comparison to linear small molecules superior pharmacological properties. Consequently, macrocyclic proteasome inhibitors might represent promising small molecules for drug development. Here, we want to highlight the current state of the art of macrocyclic proteasome inhibitor research. To this end, we give an overview and critically discuss currently known classes of macrocyclic proteasome inhibitors. PMID- 22050754 TI - SRC kinase inhibitors: an update on patented compounds. AB - The cytoplasmatic tyrosine in kinase c-Src is involved in the regulation of several cell functions including adhesion, invasion, proliferation, survival and angiogenesis. Src activity is strictly regulated in healthy cells, whereas its overexpression or hyperactivation plays a critical role during tumor development. Recently it has been suggested that the oncogenic potential of Src is linked to its role in the activation of key signalling molecules involved in several cell pathways, rather than its direct activity. For all these reasons Src represents a promising therapeutic target for the treatment of tumors. In this article a number of examples of c-Src inhibitors appeared in selected patents from 2006 to early 2011 will be reported, focusing on their chemical features and, whenever possible, on structure- activity relationships and mechanism of action. Examples of type I or II ATP-competitive inhibitors or substrate competitive inhibitors will be presented. The research in this field is very active and will probably lead to the discovery of therapeutically useful compounds, both c-Src selective and multitargeted inhibitors, that acting on different cell pathways could be more effective in blocking cancer development. However, only the results of clinical trials will show in the near future the most promising compounds. PMID- 22050755 TI - Toll-like receptor agonists as adjuvants for HIV vaccines. AB - Toll-like receptors (TLRs) are pattern-recognition receptors responsible for detecting invading pathogens. About 13 TLRs are currently known to be expressed (see Table 1). TLR2 detects lipotechoic acid and bacterial lipoproteins, TLR4 recognizes LPS, TLR5, flagellin and TLR3 detects double-stranded RNA. The unmethylated CPG DNA of bacteria and viruses is detected by TLR9. TLR7 recognizes single-stranded RNA of viruses. TLR 11 in mice recognizes profillin from Toxoplasma gondii. Binding to TLRs expressed on dendritic cells (DCs) can trigger adaptive immune responses and DCs thus serve as a bridge between innate and adaptive immunity. In HIV, it has been shown that polymorphism of the TLR9, 4, 7 and 8 plays a role in disease progression and viral load. In addition, several researchers began investigating using TLR agonists as adjuvants for HIV vaccine candidates. TLR3 has shown good results if used with vaccine proteins selectively delivered to DCs by antibodies to DEC-205/CD205, a receptor for antigen presentation. TLR7/8 and TLR9 agonists enhanced immune responses if conjugated to the vaccine protein. A triple combination of TLR2/6, -3, and -9 agonists and IL 15 synergistically up regulated immune responses to vaccine formulated as recombinant MVA viruses expressing SIVmac239 Gag, Pol, Env and Rev, Tat, Nef. These and other studies are just beginning to unravel the potential of TLRs agonists and much more and broader research is needed in order to revitalize the field of HIV vaccines. PMID- 22050757 TI - Functional non-synonymous polymorphisms prediction methods: current approaches and future developments. AB - Non-synonymous single nucleotide polymorphisms (nsSNPs) are genetic variations that affect the encoded protein by an amino acid change. In humans, many naturally-occurring nsSNPs cause protein dysfunction and increase vulnerability to disease. Identification of such nsSNPs provides an important opportunity to develop drugs/nutrients with precise therapeutic targets. Therefore, current biomedical research and medicinal chemistry look for targets and functional nsSNPs, to establish correlation with disease susceptibility and foster rational drug design. We review the molecular bases of missense mutation effects at the protein level, namely on sequence conservation, including stability, conformation, biophysical parameters, and protein-protein interaction. Further, we summarize some computational methods, available information resources, and the current approaches used to predict nsSNPs functionality in human genome, most of which based on protein structures and/or evolutionary conservation. Finally, using an approach paradigmatic of the nsSNPs-gene interactions, we evaluate the functional consequences and phenotypic effects of nsSNPs on two genes associated with cholesterol response. Biophysical changes produced by exchanged amino acids I638V (rs5908) from the 3-hydroxy-3-methylglutaryl- coenzyme A reductase gene, and A370T (rs11669576) from the low density lipoprotein receptor gene have been analyzed with an emphasis on stability, activity, and structure of their related proteins. Based on available data and the results of our study, we propose that, even though the extent and precise nature of nsSNPs' role in health and disease is yet to be fully elucidated, targeted investigations are warranted and will--in the future--provide useful tools to develop targeted drugs. PMID- 22050758 TI - Antimicrobial proteins from snake venoms: direct bacterial damage and activation of innate immunity against Staphylococcus aureus skin infection. AB - The innate immune system is the first line of defense against microbial diseases. Antimicrobial proteins produced by snake venoms have recently attracted significant attention due to their relevance to bacterial infection and potential development into new therapeutic agents. Staphylococcus aureus is one of the major human pathogens causing a variety of infections involving pneumonia, toxic shock syndrome, and skin lesions. With the recent emergence of methicillin (MRSA) and vancomycin (VRSA) resistance, S. aureus infection is a serious clinical problem that will have a grave socio-economic impact in the near future. Although S. aureus susceptibility to innate antimicrobial peptides has been reported recently, the protective effect of snake venom phospholipase A2 (svPLA2) proteins on the skin from S. aureus infection has been understudied. This review details the protective function of svPLA2s derived from venoms against skin infections caused by S. aureus. We have demonstrated in vivo that local application of svPLA2 provides complete clearance of S. aureus within 2 weeks after treatment compared to fusidic acid ointment (FAO). In vitro experiments also demonstrate that svPLA2 proteins have inhibitory (bacteriostatic) and killing (bactericidal) effects on S. aureus in a dose-dependant manner. The mechanism of bacterial membrane damage and perturbation was clearly evidenced by electron microscopic studies. In summary, svPLA2s from Viperidae and Elapidae snakes are novel molecules that can activate important mechanisms of innate immunity in animals to endow them with protection against skin infection caused by S. aureus. PMID- 22050756 TI - New developments in vaccines, inhibitors of anthrax toxins, and antibiotic therapeutics for Bacillus anthracis. AB - Bacillus anthracis, the causative agent responsible for anthrax infections, poses a significant biodefense threat. There is a high mortality rate associated with untreated anthrax infections; specifically, inhalation anthrax is a particularly virulent form of infection with mortality rates close to 100%, even with aggressive treatment. Currently, a vaccine is not available to the general public and few antibiotics have been approved by the FDA for the treatment of inhalation anthrax. With the threat of natural or engineered bacterial resistance to antibiotics and the limited population for whom the current drugs are approved, there is a clear need for more effective treatments against this deadly infection. A comprehensive review of current research in drug discovery is presented in this article, including efforts to improve the purity and stability of vaccines, design inhibitors targeting the anthrax toxins, and identify inhibitors of novel enzyme targets. High resolution structural information for the anthrax toxins and several essential metabolic enzymes has played a significant role in aiding the structure-based design of potent and selective antibiotics. PMID- 22050759 TI - The state of the art of pyrazole derivatives as monoamine oxidase inhibitors and antidepressant/anticonvulsant agents. AB - Monoamine oxidase plays a significant role in the control of intracellular concentration of monoaminergic neurotransmitters or neuromodulators and dietary amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critically important for the regulation of emotional and other brain functions. The development of human MAO inhibitors led to important breakthroughs in the therapy of several neuropsychiatric disorders. Different families of heterocycles containing 2 or 4 nitrogen atoms have been used as scaffolds for synthesizing selective monoamine oxidase inhibitors, but the early period of the MAO-inhibitors started with hydrazine derivatives. Pyrazole, pyrazoline, and pyrazolidine derivatives can be considered as a cyclic hydrazine moiety. This scaffold also displayed promising antidepressant and anticonvulsant properties as demonstrated by different and established animal models. Diversely substituted pyrazoles, embedded with a variety of functional groups, are important biological agents and a significant amount of research activity has been directed towards this chemical class. PMID- 22050760 TI - Chemical connexin impairment in the developing gonad associated with offspring infertility. AB - A dramatical decline in human male reproductive function has been reported for the past 20 years. Many recent epidemiological, clinical and experimental findings suggest that the reproductive dysfunction could result from prenatal and neonatal chemical compound exposure. Even if numerous studies argue for a relationship between male infertility and environmental and/or occupational exposure, the molecular mechanisms by which these anti-reproductive compounds act are still unclear. Recent findings showed that a family of transmembranous proteins, connexins, regulates numerous physiological functions involved in the development such as cell proliferation, differentiation, migration and apoptosis. In the testis and the ovary, connexins are known to be essential for the establishment and the maintenance of spermatogenesis in males and oogenesis and folliculogenesis in females. Moreover, mutation of connexin genes leads to several developmental human diseases (myelin-related diseases, hearing loss, congenital cataract, skin disorders or more complex syndromes such as the oculodendrodigital dysplasia....) and altered connexin expression, trafficking and degradation are often associated with the tumoral process. We propose, in the present work, to give an overview of connexin expression and intercellular gap junction coupling during development: in preimplantation, implantation and postimplantation embryos. Moreover, we underline the impact of maternal chemical exposure on connexin expression during fetal gonad development and we link this effect to future offspring fertility. PMID- 22050761 TI - Novel treatment options of binge eating disorder. AB - Obesity is a major problem of modern societies that sometimes, but not necessarily, is associated with binge-eating disorder (BED), a relatively new disorder characterized by binge eating without purging. The purpose of this article is to review the rationale for the potential use of pharmacological treatments in BED, and the potential use of the recently proposed compounds. Therefore, a careful medline of published articles from 1980 to December 2010 was carried out using the following keywords: BED and treatment, topiramate, zonisamide, sibutramine, venlafaxine, duloxetine, ghrelin, opiate blockers. Single case reports, observational studies, opinion articles, and studies concerning adults with syndromes resulting in BED (i.e., night eating syndrome) were also reviewed. All examined papers would indicate that the pharmacological treatment of BED is still heterogenous and poorly established, mainly for the lack of controlled studies in large samples of patients. In any case, the data on serotonin and norepinephrine reuptake inhibitors and on novel anticonvulsants seem quite promising in terms of efficacy and tolerability. In addition, the preliminary findings on the possibility of modulating appetite through the interference with the ghrelin system suggest new and intriguing ways of intervention in BED. PMID- 22050762 TI - A new combined therapeutic strategy of governor vessel electro-acupuncture and adult stem cell transplantation promotes the recovery of injured spinal cord. AB - Spinal cord injury (SCI) is a very severe traumatic disease of the central nervous system (CNS). Because of its high incidence rate in causing disabilities, it brings great burdens to patients and society. Both Traditional Chinese Medicine (TCM) and Western Medicine have been adopted to ameliorate SCI with promising outcomes. In TCM, the use of Governor Vessel electro-acupuncture has achieved remarkable results on the rehabilitation of patients with SCI. In the past decade, Governor Vessel electro-acupuncture has also been used in experimentally induced SCI and this has resulted in promising functional recovery. Both neural stem cells (NSCs) and bone marrow mesenchymal cells (MSCs) have been used extensively in recent years for improvement of functional recovery of CNS disorders. We have used a combined approach by integrating the basic and clinical research in SCI in recent years. In this connection, transplantation of NSCs or MSCs coupled with the Governor Vessel electro-acupuncture (GV-EA) has been adopted to improve the recovery of SCI. Our study suggests that GV-EA may activate the process of cell metabolism, and initiate synthesis and secretion of endogenous neurotrophic factors in the ambient tissues at the lesion site of spinal cord. It is proposed that the new combined strategy could promote a better structural and functional recovery of injured spinal cord. PMID- 22050763 TI - PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies. AB - The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34(+) cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies. PMID- 22050764 TI - Novel genetic reassortants in H9N2 influenza A viruses and their diverse pathogenicity to mice. AB - BACKGROUND: H9N2 influenza A viruses have undergone extensive reassortments in different host species, and could lead to the epidemics or pandemics with the potential emergence of novel viruses. METHODS: To understand the genetic and pathogenic features of early and current circulating H9N2 viruses, 15 representative H9N2 viruses isolated from diseased chickens in northern China between 1998 and 2010 were characterized and compared with all Chinese H9N2 viruses available in the NCBI database. Then, the representative viruses of different genotypes were selected to study the pathogenicity in mice with the aim to investigate the adaptation and the potential pathogenicity of the novel H9N2 reassortants to mammals. RESULTS: Our results demonstrated that most of the 15 isolates were reassortants and generated four novel genotypes (B62-B65), which incorporated the gene segments from Eurasian H9N2 lineage, North American H9N2 branch, and H5N1 viruses. It was noteworthy that the newly identified genotype B65 has been prevalent in China since 2007, and more importantly, different H9N2 influenza viruses displayed a diverse pathogenicity to mice. The isolates of the 2008-2010 epidemic (genotypes B55 and B65) were lowly infectious, while two representative viruses of genotypes B0 and G2 isolated from the late 1990s were highly pathogenic to mice. In addition, Ck/SD/LY-1/08 (genotype 63, containing H5N1-like NP and PA genes) was able to replicate well in mouse lungs with high virus titers but caused mild clinical signs. CONCLUSION: Several lines of evidence indicated that the H9N2 influenza viruses constantly change their genetics and pathogenicity. Thus, the genetic evolution of H9N2 viruses and their pathogenicity to mammals should be closely monitored to prevent the emergence of novel pandemic viruses. PMID- 22050765 TI - Evaluation of hexavalent chromium extraction method EPA method 3060A for soils using XANES spectroscopy. AB - Hexavalent chromium (Cr(VI)) occurrence in soils is generally determined using an extraction step to transfer it to the liquid phase where it is more easily detected and quantified. In this work, the performance of the most common extraction procedure (EPA Method 3060A) using NaOH-Na(2)CO(3) solutions is evaluated using X-ray absorption near edge structure spectroscopy (XANES), which enables the quantification of Cr(VI) directly in the solid state. Results obtained with both methods were compared for three solid samples with different matrices: a soil containing chromite ore processing residue (COPR), a loamy soil, and a paint sludge. Results showed that Cr(VI) contents determined by the two methods differ significantly, and that the EPA Method 3060A procedure underestimated the Cr(VI) content in all studied samples. The underestimation is particularly pronounced for COPR. Low extraction yield for EPA Method 3060A was found to be the main reason. The Cr(VI) present in COPR was found to be more concentrated in magnetic phases. This work provides new XANES analyses of SRM 2701 and its extraction residues for the purpose of benchmarking EPA 3060A performance. PMID- 22050766 TI - Use of a sclerosing agent (1% polidocanol) to treat an orbital mucocele in a dog. AB - A case of a salivary gland mucocele in a dog causing nonpainful exopthalmos with dorsolateral deviation of the globe and protrusion of the third eyelid. Diagnosis was made via ultrasound and confirmed with computed tomography. Aspiration of the cystic material along with injection of a sclerosing agent, 1% polidocanol (Aethoxysklerol), was used to destroy the mucocele. Follow-up monthly examination post injection confirmed resolution of clinical signs to date, namely abnormal globe position, with no complications observed. PMID- 22050767 TI - Whole-organ analysis of calcium behaviour in the developing pistil of olive (Olea europaea L.) as a tool for the determination of key events in sexual plant reproduction. AB - BACKGROUND: The pistil is a place where multiple interactions between cells of different types, origin, and function occur. Ca(2+) is one of the key signal molecules in plants and animals. Despite the numerous studies on Ca(2+) signalling during pollen-pistil interactions, which constitute one of the main topics of plant physiology, studies on Ca(2+) dynamics in the pistil during flower formation are scarce. The purpose of this study was to analyze the contents and in situ localization of Ca(2+) at the whole-organ level in the pistil of olive during the whole course of flower development. RESULTS: The obtained results showed significant changes in Ca(2+) levels and distribution during olive pistil development. In the flower buds, the lowest levels of detectable Ca(2+) were observed. As flower development proceeded, the Ca(2+) amount in the pistil successively increased and reached the highest levels just after anther dehiscence. When the anthers and petals fell down a dramatic but not complete drop in calcium contents occurred in all pistil parts. In situ Ca(2+) localization showed a gradual accumulation on the stigma, and further expansion toward the style and the ovary after anther dehiscence. At the post-anthesis phase, the Ca(2+) signal on the stigmatic surface decreased, but in the ovary a specific accumulation of calcium was observed only in one of the four ovules. Ultrastructural localization confirmed the presence of Ca(2+) in the intracellular matrix and in the exudate secreted by stigmatic papillae. CONCLUSIONS: This is the first report to analyze calcium in the olive pistil during its development. According to our results in situ calcium localization by Fluo-3 AM injection is an effective tool to follow the pistil maturity degree and the spatial organization of calcium-dependent events of sexual reproduction occurring in developing pistil of angiosperms. The progressive increase of the Ca(2+) pool during olive pistil development shown by us reflects the degree of pistil maturity. Ca(2+) distribution at flower anthesis reflects the spatio functional relationship of calcium with pollen-stigma interaction, progamic phase, fertilization and stigma senescence. PMID- 22050769 TI - Reference values for Schirmer tear tests I and II in clinically normal pigs. AB - OBJECTIVE: To determine reference values for Schirmer tear tests I and II in clinically normal pigs. ANIMAL STUDIED: Twenty clinically normal Landrace pigs (10 males and females) without ocular abnormalities were used in this study. PROCEDURES: In all pigs, Schirmer tear tests (STT) I and II were performed by using a sterile Schirmer tear test standardized strip (Schirmer-Tranentest((r)), Germany) placed in the lower conjunctival fornix for 1 min. RESULTS: For each test (STT I and STT II), no differences were observed between the right and left eyes (P >= 0.5). The mean +/- SD STT I value was 15.6 +/- 3.7 mm/min (range, 10 22 mm/min), while the mean STT II value was 12.4 +/- 3.8 mm/minute (range, 5-18 mm/min). The mean STT II value was significantly lower than the STT I level (P < 0.001). Animal gender did not have a significant effect on STT I and II values (P = 0.52). The mean +/- SD STT I/II values of 10 juvenile pigs were significantly lower than the mean +/- SD STT I/II values of 10 adult pigs (P < 0.001). CONCLUSIONS: This study of 20 Landrace pigs provided valuable information on normal STT I/II in this species. Knowledge of normal STT reference values in pigs enables the clinician to evaluate corneal pathology and diagnose tear deficiency syndromes with greater accuracy. PMID- 22050768 TI - Protein trafficking, ergosterol biosynthesis and membrane physics impact recombinant protein secretion in Pichia pastoris. AB - BACKGROUND: The increasing availability of 'omics' databases provide important platforms for yeast engineering strategies since they offer a lot of information on the physiology of the cells under diverse growth conditions, including environmental stresses. Notably, only a few of these approaches have considered a performance under recombinant protein production conditions. Recently, we have identified a beneficial effect of low oxygen availability on the expression of a human Fab fragment in Pichia pastoris. Transcriptional analysis and data mining allowed for the selection of potential targets for strain improvement. A first selection of these candidates has been evaluated as recombinant protein secretion enhancers. RESULTS: Based on previous transcriptomics analyses, we selected 8 genes for co-expression in the P. pastoris strain already secreting a recombinant Fab fragment. Notably, WSC4 (which is involved in trafficking through the ER) has been identified as a novel potential target gene for strain improvement, with up to a 1.2-fold increase of product yield in shake flask cultures. A further transcriptomics-based strategy to modify the yeast secretion system was focused on the ergosterol pathway, an aerobic process strongly affected by oxygen depletion. By specifically partially inhibiting ergosterol synthesis with the antifungal agent fluconazole (inhibiting Erg11p), we tried to mimic the hypoxic conditions, in which the cellular ergosterol content was significantly decreased. This strategy led to an improved Fab yield (2-fold) without impairing cellular growth. Since ergosterol shortage provokes alterations in the plasma membrane composition, an important role of this cellular structure in protein secretion is suggested. This hypothesis was additionally supported by the fact that the addition of non-ionic surfactants also enhanced Fab secretion. CONCLUSIONS: The current study presents a systems biotechnology-based strategy for the engineering of the industrially important yeast P. pastoris combining the use of host specific DNA microarray technologies and physiological studies under well defined environmental conditions. Such studies allowed for the identification of novel targets related with protein trafficking and ergosterol biosynthesis for improved recombinant protein production. Nevertheless, further studies will be required to elucidate the precise mechanisms whereby membrane biogenesis and composition impact on protein secretion in P. pastoris. PMID- 22050770 TI - Developing a dimensional model for successful cognitive and emotional aging. AB - BACKGROUND: There is currently a lack of consensus on the definition of successful aging (SA) and existing implementations have omitted constructs associated with SA. We used empirical methods to develop a dimensional model of SA that incorporates a wider range of associated variables, and we examined the relationship among these components using factor analysis and Bayesian Belief Nets. METHODS: We administered a successful aging questionnaire comprising several standardized measures related to SA to a sample of 1948 older women enrolled in the San Diego site of the Women's Health Initiative study. The SA related variables we included in the model were self-rated successful aging, depression severity, physical and emotional functioning, optimism, resilience, attitude towards own aging, self-efficacy, and cognitive ability. After adjusting for age, education and income, we fitted an exploratory factor analysis model to the SA-related variables and then, in order to address relationships among these factors, we computed a Bayesian Belief Net (BBN) using rotated factor scores. RESULTS: The SA-related variables loaded onto five factors. Based on the loading, we labeled the factors as follows: self-rated successful aging, cognition, psychosocial protective factors, physical functioning, and emotional functioning. In the BBN, self-rated successful aging emerged as the primary downstream factor and exhibited significant partial correlations with psychosocial protective factors, physical/general status and mental/emotional status but not with cognitive ability. CONCLUSIONS: Our study represents a step forward in developing a dimensional model of SA. Our findings also point to a potential role for psychiatry in improving successful aging by managing depressive symptoms and developing psychosocial interventions to improve self-efficacy, resilience, and optimism. PMID- 22050771 TI - Excess folate during adolescence suppresses thyroid function with permanent deficits in motivation and spatial memory. AB - Cognitive and memory deficits can be caused or exacerbated by dietary folate deficiency, which has been combatted by the addition of folate to grains and dietary supplements. The recommended dose of the B9 vitamin folate is 400 ug/day for adolescents and non-pregnant adults, and consumption above the recommended daily allowance is not considered to be detrimental. However, the effects of excess folate have not been tested in adolescence when neuro and endocrine development suggest possible vulnerability to long-term cognitive effects. We administered folate-supplemented (8.0 mg folic acid/kg diet) or control lab chow (2.7 mg folic acid/kg diet) to rats ad libitum from 30 to 60 days of age, and subsequently tested their motivation and learning and memory in the Morris water maze. We found that folate-supplemented animals had deficits in motivation and spatial memory, but they showed no changes of the learning- and memory-related molecules growth-associated protein-43 or Gs-alpha subunit protein in the hippocampus. They had decreased levels of thyroxine (T4) and triiodothyronine (T3) in the periphery and decreased protein levels of thyroid receptor-alpha1 and -alpha2 (TRalpha1 and TRalpha2) in the hippocampus. The latter may have been due to an observed increase of cytosine-phosphate-guanosine island methylation within the putative thyroid hormone receptor-alpha promoter, which we have mapped for the first time in the rat. Overall, folate supplementation in adolescence led to motivational and spatial memory deficits that may have been mediated by suppressed thyroid hormone function in the periphery and hippocampus. PMID- 22050772 TI - PE_PGRS30 is required for the full virulence of Mycobacterium tuberculosis. AB - The role and function of PE_PGRS proteins of Mycobacterium tuberculosis (Mtb) remains elusive. In this study for the first time, Mtb isogenic mutants missing selected PE_PGRSs were used to investigate their role in the pathogenesis of tuberculosis (TB). We demonstrate that the MtbDeltaPE_PGRS30 mutant was impaired in its ability to colonize lung tissue and to cause tissue damage, specifically during the chronic steps of infection. Inactivation of PE_PGRS30 resulted in an attenuated phenotype in murine and human macrophages due to the inability of the Mtb mutant to inhibit phagosome-lysosome fusion. Using a series of functional deletion mutants of PE_PGRS30 to complement MtbDeltaPE_PGRS30, we show that the unique C-terminal domain of the protein is not required for the full virulence. Interestingly, when Mycobacterium smegmatis recombinant strain expressing PE_PGRS30 was used to infect macrophages or mice in vivo, we observed enhanced cytotoxicity and cell death, and this effect was dependent upon the PGRS domain of the protein.Taken together these results indicate that PE_PGRS30 is necessary for the full virulence of Mtb and sufficient to induce cell death in host cells by the otherwise non-pathogenic species M. smegmatis, clearly demonstrating that PE_PGRS30 is an Mtb virulence factor. PMID- 22050773 TI - Editorial comment to effect of constipation on serum total prostate-specific antigen levels in men. PMID- 22050774 TI - Isocyanide-based multicomponent reactions: synthesis of alkyl-2-(1 (alkylcarbamoyl)-2,2-dicyanoethyl)benzoate and isochromeno[3,4-b]pyrrole derivatives. AB - A novel four-component reaction between 2-formylbenzoic acids, malononitrile, isocyanides, and alcohols has been developed for a highly efficient preparation of alkyl-2-(1-(alkylcarbamoyl)-2,2-dicyanoethyl)benzoate derivatives. This high atom economy reaction led to the construction of two carbon-carbon bonds, one amide, and one ester group in a single synthetic step. Furthermore, a three component reaction between 2-formylbenzoic acids, malononitrile, and isocyanides in dichloromethane for the preparation of isochromeno[3,4-b]pyrroles has been reported. PMID- 22050775 TI - Are causal structure and intervention judgments inextricably linked? A developmental study. AB - The application of the formal framework of causal Bayesian Networks to children's causal learning provides the motivation to examine the link between judgments about the causal structure of a system, and the ability to make inferences about interventions on components of the system. Three experiments examined whether children are able to make correct inferences about interventions on different causal structures. The first two experiments examined whether children's causal structure and intervention judgments were consistent with one another. In Experiment 1, children aged between 4 and 8 years made causal structure judgments on a three-component causal system followed by counterfactual intervention judgments. In Experiment 2, children's causal structure judgments were followed by intervention judgments phrased as future hypotheticals. In Experiment 3, we explicitly told children what the correct causal structure was and asked them to make intervention judgments. The results of the three experiments suggest that the representations that support causal structure judgments do not easily support simple judgments about interventions in children. We discuss our findings in light of strong interventionist claims that the two types of judgments should be closely linked. PMID- 22050776 TI - Epigenetic control of CCR5 transcript levels in immune cells and modulation by small molecules inhibitors. AB - Previously, we have shown that CCR5 transcription is regulated by CREB-1. However, the ubiquitous pattern of CREB-1 expression suggests the involvement of an additional level of transcriptional control in the cell type-specific expression of CCR5. In this study, we show that epigenetic changes (i.e. DNA methylation and histone modifications) within the context of the CCR5 P1 promoter region correlate with transcript levels of CCR5 in healthy and in malignant CD4(+) T lymphocytes as well as in CD14(+) monocytes. In normal naive T cells and CD14(+) monocytes the CCR5 P1 promoter resembles a bivalent chromatin state, with both repressive and permissive histone methylation and acetylation marks. The CCR5-expressing CD14(+) monocytes however show much higher levels of acetylated histone H3 (AcH3) compared to the non-CCR5-expressing naive T cells. Combined with a highly methylated promoter in CD14(+) monocytes, this indicates a dominant role for AcH3 in CCR5 transcription. We also show that pharmacological interference in the epigenetic repressive mechanisms that account for the lack of CCR5 transcription in T leukaemic cell lines results in an increase in CREB-1 association with CCR5 P1 chromatin. Furthermore, RNA polymerase II was also recruited into CCR5 P1 chromatin resulting in CCR5 re-expression. Together, these data indicate that epigenetic modifications of DNA, and of histones, contribute to the control of CCR5 transcription in immune effector cells. PMID- 22050778 TI - Role of five-fold twin boundary on the enhanced mechanical properties of fcc Fe nanowires. AB - The role of 5-fold twin boundary on the structural and mechanical properties of fcc Fe nanowire under tension is explored by classical molecular dynamics. Twin stabilized fcc nanowire with various diameters (6-24 nm) are examined by tension tests at several temperatures ranging from 0.01 to 1100 K. Significant increase in the Young's modulus of the smaller nanowires is revealed to originate from the central area of quinquefoliolate-like stress-distribution over the 5-fold twin, rather than from the surface tension that is often considered as the main source of such size-effects found in nanostructures. Because of the excess compressive stress caused by crossing twin-boundaries, the atoms in the center behave stiffer than those in bulk and even expand laterally under axial tension, providing locally negative Poisson's ratio. The yield strength of nanowire is also enhanced by the twin boundary that suppresses dislocation nucleation within a fcc twin domain; therefore, the plasticity of nanowire is initiated by strain-induced fcc >bcc phase transformation that destroys the twin structure. After the yield, the nucleated bcc phase immediately spreads to the entire area, and forms a multigrain structure to realize ductile deformation followed by necking. As temperature elevated close to the critical temperature between bcc and fcc phases, the increased stability of fcc phase competes with the phase transformation under tension, and hence dislocation nucleations in fcc phase are observed exclusively at the highest temperature in our study. PMID- 22050777 TI - Spectral domain optical coherence tomography (SD-OCT) assessment of the healthy female canine retina and optic nerve. AB - OBJECTIVE: To provide normative data for canine whole retinal thickness (WRT), nerve fiber layer thickness (NFL), photoreceptor layer thickness (PR), and outer nuclear layer thickness (ONL) using spectral domain optical coherence tomography. ANIMAL STUDIED: Twelve healthy adult intact female beagles. PROCEDURE: Horizontal volume scans through the area dorso-temporal from the optic nerve (superior retina), and the area ventro-temporal from the optic nerve (inferior retina) were used to evaluate the thickness of retinal NFL, PR, ONL, and WRT. Peripapillary circular scans were used to evaluate NFL thickness. Statistical analyses were performed to compare the thickness of the individual layers between the superior and inferior retina (paired t-test). One-way analysis of variance (ANOVA) was used to compare the thickness of peripapillary NFL between the superior, inferior, temporal and nasal quadrants of the circle scan. RESULTS: The WRT, PR, and NFL thickness were greater in the superior than in the inferior retina (198.7 +/- 9.6 MUm vs. 164.4 +/- 6.4 MUm, P < 0.0001; 95.5 +/- 6.5 MUm vs. 78.8 +/- 7.4 MUm, P < 0.0001; and 26.4 +/- 1.6 MUm vs. 25.0 +/- 1.9 MUm, P = 0.0236, respectively). No statistical difference was found between the ONL thickness of the superior and inferior retina (50.1 +/- 6.4 MUm vs. 44.3 +/- 3.6, P = 0.0578). Peripapillary NFL thickness showed a similar tendency as the linear scans, with the superior quadrant having the greatest thickness (91.26 +/- 7.0 MUm) and the inferior quadrant being the thinnest (76.42 +/- 9.2 MUm) (P < 0.001). CONCLUSIONS: Results of our in vivo studies showed significant differences between thickness values for the superior (tapetal) and inferior (nontapetal) retinal regions. PMID- 22050779 TI - Recovery of pure ZnO nanoparticles from spent Zn-MnO2 alkaline batteries. AB - The recovery of pure ZnO (zinc oxide) nanoparticles from spent Zn-Mn dry alkaline batteries is reported. Spent batteries were dismantled to separate the contained valuable metals of the cell electrodes in the form of black powder. Treatment of this black powder with 5 mol L(-1) HCl produced leach liquor, primarily containing 2.90 g L(-1) Zn and 2.02 g L(-1) Mn. Selective and quantitative liquid liquid extraction of Zn(II) was then carried out in three counter current steps by using Cyanex 923 (0.10 mol L(-1) in n-hexane). Zn(II) distributed in the organic phase as complex ZnCl(2).2R (R = Cyanex 923 molecule). The metal loaded organic phase was subjected to combust at 600 degrees C to yield pure ZnO nanoparticles (40-50 nm). Important characteristics of the synthesized nanoparticles were investigated by field emission scanning electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction spectroscopy (XRD), and atomic force microscopy (AFM). PMID- 22050780 TI - Exploration of the pathogenesis of haemophilic joint arthropathy: understanding implications for optimal clinical management. AB - Haemophilia is an inherited disorder of clotting factor deficiencies resulting in musculoskeletal bleeding, including haemarthroses, leading to orthopaedic complications. The pathogenesis of haemophilic joint arthropathy continues to be explored and there is evidence to suggest that iron, cytokines, and neo angiogenesis can initiate synovial and early cartilage damage resulting in molecular changes and the perpetuation of a chronic inflammatory state. This joint arthropathy has long term consequences for bone health resulting in chronic pain and quality of life issues in the individual with haemophilia. Haemarthroses can be prevented by the administration of clotting factor concentrates (prophylaxis). However, high costs and the need for venous access devices in younger children continue to complicate recommendations for universal prophylaxis. In patients who fail or refuse prophylaxis, procedures, such as synovectomy and arthroplasty, can provide relief from repeated haemarthroses. The optimal timing of these, however, is not well defined. Prevention of joint arthropathy needs to focus on prevention of haemarthroses through prophylaxis, identifying early joint disease through the optimal use of cost effective imaging modalities and the validation of serological markers of joint arthropathy. Screening for effects on bone health and optimal management of pain to improve quality of life are, likewise, important issues. PMID- 22050781 TI - Regressed three-dimensional capillary network and inhibited angiogenic factors in the soleus muscle of non-obese rats with type 2 diabetes. AB - Based on findings obtained using two-dimensional capillary analyses on tissue cross-sections, diabetes has been shown to be associated with a high risk for microangiopathy and capillary regression in skeletal muscles. We visualized the three-dimensional architecture of the capillary networks in the soleus muscle of non-obese Goto-Kakizaki (GK) rats with type 2 diabetes and compared them with those of control Wistar rats to provide novel information, e.g., capillary volume, on the capillary networks. In addition, we examined pro- and anti angiogenic gene expression levels in the soleus muscle of GK rats using TaqMan probe-based real-time PCR. As expected, plasma glucose levels were higher and insulin levels lower in GK than control rats. The three-dimensional architecture of the capillary networks was regressed and capillary volume was smaller in the soleus muscle of GK compared to control rats. The mRNA expression levels of the pro-angiogenic factors HIF-1alpha, KDR, Flt-1, ANG-1, and Tie-2 were lower, whereas the level of the anti-angiogenic factor TSP-1 was higher in GK than control rats. These data suggest that a decrease in pro-angiogenic and increase in anti-angiogenic factors may play an important role in type 2 diabetes-induced muscle circulatory complications. PMID- 22050782 TI - Morphology of retinal vessels in the optic disk in a Gottingen minipig experimental glaucoma model. AB - OBJECTIVE: To compare the morphology of normal, healthy Gottingen minipig retinal vessels of the optic disk with experimentally induced glaucomatous optic disks in order to identify the glaucomatous excavation. Present results were compared to human glaucoma findings. PROCEDURE: Sixteen eyes from eight Gottingen minipigs were studied using fundoscopic photography and fluorescein angiography. Experimental glaucoma was then induced in the left eyes over 14 months, and changes in the optic disk vessels were assessed using fundoscopic photography and fluorescein angiography. The changes were compared with those previously reported in humans. RESULTS: Regarding the number of vessels, the location from where they emerge and the sectors of the optic disk that they cross, arterial and retinal vessels in Gottingen minipigs present a more asymmetric layout than in humans. The central excavation is filled by the central venous ring. Changes in the glaucomatous optic disk include arteriolar incurvation, and sometimes, nasal, and peripheral displacement of the arterioles that emerge between the ganglion cell axons of the neuroretinal ring. No angiographic changes were observed in the experimental glaucoma model. CONCLUSIONS: The changes in the glaucomatous optic disk of the minipig imply a predominant involvement of the arterioles. However, in humans with primary open-angle glaucoma (POAG), both the arterioles and the venules are displaced, and the central excavation is easier to distinguish, because of the absence of a central venous ring. PMID- 22050783 TI - A highly conserved NB-LRR encoding gene cluster effective against Setosphaeria turcica in sorghum. AB - BACKGROUND: The fungal pathogen Setosphaeria turcica causes turcicum or northern leaf blight disease on maize, sorghum and related grasses. A prevalent foliar disease found worldwide where the two host crops, maize and sorghum are grown. The aim of the present study was to find genes controlling the host defense response to this devastating plant pathogen. A cDNA-AFLP approach was taken to identify candidate sequences, which functions were further validated via virus induced gene silencing (VIGS), and real-time PCR analysis. Phylogenetic analysis was performed to address evolutionary events. RESULTS: cDNA-AFLP analysis was run on susceptible and resistant sorghum and maize genotypes to identify resistance related sequences. One CC-NB-LRR encoding gene GRMZM2G005347 was found among the up-regulated maize transcripts after fungal challenge. The new plant resistance gene was designated as St referring to S. turcica. Genome sequence comparison revealed that the CC-NB-LRR encoding St genes are located on chromosome 2 in maize, and on chromosome 5 in sorghum. The six St sorghum genes reside in three pairs in one locus. When the sorghum St genes were silenced via VIGS, the resistance was clearly compromised, an observation that was supported by real time PCR. Database searches and phylogenetic analysis suggest that the St genes have a common ancestor present before the grass subfamily split 50-70 million years ago. Today, 6 genes are present in sorghum, 9 in rice and foxtail millet, respectively, 3 in maize and 4 in Brachypodium distachyon. The St gene homologs have all highly conserved sequences, and commonly reside as gene pairs in the grass genomes. CONCLUSIONS: Resistance genes to S. turcica, with a CC-NB-LRR protein domain architecture, have been found in maize and sorghum. VIGS analysis revealed their importance in the surveillance to S. turcica in sorghum. The St genes are highly conserved in sorghum, rice, foxtail millet, maize and Brachypodium, suggesting an essential evolutionary function. PMID- 22050785 TI - Natural history of prenatal ventricular septal defects and their association with foetal echocardiographic features. AB - OBJECTIVE: To describe the evolution of ventricular septal defects in infants from intra-uterine diagnosis to the age of 3 years or until documented echocardiographic closure of the defect, as well as any relationship between closure rate, time and foetal echocardiographic features. METHODS: Between January, 2004 and December, 2006, 268 cases of congenital cardiac defect were detected in 14,993 pregnancies referred to our hospital for routine foetal echocardiography; of these cases, 125 had isolated ventricular septal defect. The mothers were scheduled for regular ultrasonography every 2 weeks from diagnosis until the ventricular septal defect closed or 3 years postnatally. RESULTS: Of the 125 cases of ventricular septal defects, the pregnancy was terminated in 25, four resulted in death, two defects closed spontaneously in utero, 55 closed at a mean age of 13.7 months postnatally, 17 were treated with surgery, nine remained unclosed, and 13 cases were lost to follow-up. Only 7.7% of muscular ventricular septal defects remained patent as compared with 35.7% of perimembranous ventricular septal defects (p is less than 0.01). Muscular ventricular septal defects closed earlier than perimembranous ventricular septal defects. All the ventricular septal defects less than or equal to 3 millimetres closed, whereas only 79.5% of the defects greater than 3 millimetres closed before the age of 3 years; 60.9% of the defects less than or equal to 3 millimetres closed before the age of 1 year as compared with 41.7% of the defects greater than 3 millimetres. The velocity of right-to-left flow was negatively correlated with closure rate but not related to closure period. CONCLUSION: Ventricular septal defects can close in utero or during the postnatal period, and both the size and site play a role in the natural history, with small and muscular ventricular septal defects having a high closure rate and early closure. PMID- 22050784 TI - Molecular cloning, expression and biochemical characterisation of a cold-adapted novel recombinant chitinase from Glaciozyma antarctica PI12. AB - BACKGROUND: Cold-adapted enzymes are proteins produced by psychrophilic organisms that display a high catalytic efficiency at extremely low temperatures. Chitin consists of the insoluble homopolysaccharide beta-(1, 4)-linked N acetylglucosamine, which is the second most abundant biopolymer found in nature. Chitinases (EC 3.2.1.14) play an important role in chitin recycling in nature. Biodegradation of chitin by the action of cold-adapted chitinases offers significant advantages in industrial applications such as the treatment of chitin rich waste at low temperatures, the biocontrol of phytopathogens in cold environments and the biocontrol of microbial spoilage of refrigerated food. RESULTS: A gene encoding a cold-adapted chitinase (CHI II) from Glaciozyma antarctica PI12 was isolated using Rapid Amplification of cDNA Ends (RACE) and RT PCR techniques. The isolated gene was successfully expressed in the Pichia pastoris expression system. Analysis of the nucleotide sequence revealed the presence of an open reading frame of 1,215 bp, which encodes a 404 amino acid protein. The recombinant chitinase was secreted into the medium when induced with 1% methanol in BMMY medium at 25 degrees C. The purified recombinant chitinase exhibited two bands, corresponding to the non-glycosylated and glycosylated proteins, by SDS-PAGE with molecular masses of approximately 39 and 50 kDa, respectively. The enzyme displayed an acidic pH characteristic with an optimum pH at 4.0 and an optimum temperature at 15 degrees C. The enzyme was stable between pH 3.0-4.5 and was able to retain its activity from 5 to 25 degrees C. The presence of K+, Mn2+ and Co2+ ions increased the enzyme activity up to 20%. Analysis of the insoluble substrates showed that the purified recombinant chitinase had a strong affinity towards colloidal chitin and little effect on glycol chitosan. CHI II recombinant chitinase exhibited higher Vmax and Kcat values toward colloidal chitin than other substrates at low temperatures. CONCLUSION: By taking advantage of its high activity at low temperatures and its acidic pH optimum, this recombinant chitinase will be valuable in various biotechnological applications under low temperature and acidic pH conditions. PMID- 22050786 TI - Effect of initial combination therapy with sitagliptin and metformin on beta-cell function in patients with type 2 diabetes. AB - AIM: To examine the effect of sitagliptin and metformin, alone and in combination, on modelled parameters of beta-cell function in patients with type 2 diabetes. METHODS: The data used in the present analyses are from a 104-week study, which included a 24-week, placebo- and active controlled phase followed by a 30-week, active controlled, continuation phase and an additional 50-week, active controlled extension phase. Patients were randomised to one of six blinded treatments: sitagliptin 50 mg + metformin 1000 mg b.i.d., sitagliptin 50 mg + metformin 500 mg b.i.d., metformin 1000 mg b.i.d., metformin 500 mg b.i.d., sitagliptin 100 mg q.d. or placebo. Patients on placebo were switched in a blinded manner to metformin 1000 mg b.i.d. at week 24. Subsets of patients volunteered to undergo frequently sampled meal tolerance tests at baseline and at weeks 24, 54 and 104. beta-cell responsivity was assessed with the C-peptide minimal model. The static component (Phi(s)) estimates the rate of insulin secretion related to above-basal glucose concentration. The dynamic component (Phi(d)) is related to the rate of change in glucose. The total index (Phi(total)) represents the overall response to a glycaemic stimulus and is calculated as a function of Phi(s) and Phi(d). Insulin sensitivity was estimated with the Matsuda index (ISI). The disposition index, which assesses insulin secretion relative to the prevailing insulin sensitivity, was calculated based on the Phi(total) and ISI. RESULTS: At week 24, substantial reductions in postmeal glucose were observed with all active treatment groups relative to the placebo group. Phi(s), Phi(total) and the disposition index were significantly improved from baseline at week 24 with all active treatments relative to placebo. Generally larger effects were observed with the initial combination of sitagliptin and metformin relative to the monotherapy groups. When expressed as median percent change from baseline, Phi(s) increased from baseline by 137 and 177% in the low- and high-dose combination groups and by 85, 54, 73 and -9% in the high-dose metformin, low-dose metformin, sitagliptin monotherapy and placebo groups, respectively. At weeks 54 and 104, the combination treatment groups continued to demonstrate greater improvements in beta-cell function relative to their respective monotherapy groups. CONCLUSIONS: After 24 weeks of therapy, relative to placebo, initial treatment with sitagliptin or metformin monotherapy improved beta-cell function; moreover, initial combination therapy demonstrated larger improvements than the individual monotherapies. Improvements in beta-cell function were found with treatments for up to 2 years. PMID- 22050787 TI - Common and novel transcriptional routes to behavioral maturation in worker and male honey bees. AB - Worker honey bees (Apis mellifera) undergo a process of behavioral maturation leading to their transition from in-hive tasks to foraging--a process which is associated with profound transcriptional changes in the brain. Changes in brain gene expression observed during worker behavioral maturation could represent either a derived program underlying division of labor or a general program unrelated to sociality. Male bees (drones) undergo a process of behavioral maturation associated with the onset of mating flights, but do not partake in division of labor. Drones thus provide an excellent reference point for polarizing transcriptional changes associated with behavioral maturation in honey bees. We assayed the brain transcriptomes of adult drones and workers to compare and contrast differences associated with behavioral maturation in the two sexes. Both behavioral maturation and sex were associated with changes in expression of thousands of genes in the brain. Many genes involved in neuronal development, behavior, and the biosynthesis of neurotransmitters regulating the perception of reward showed sex-biased gene expression. Furthermore, most of the transcriptional changes associated with behavioral maturation were common to drones and workers, consistent with common genetic and physiological regulation. Our study suggests that there is a common behavioral maturation program that has been co-opted and modified to yield the different behavioral and cognitive phenotypes of worker and drone bees. PMID- 22050788 TI - Symblepharon secondary to ophthalmomyiasis externa in a dog. AB - A 4-month-old crossbred female dog presented with complaints of poor vision and odd appearance of the eyes. At the age of a month, the animal was found lying in a railway road in a very bad condition and was rescued from death. At that time, the patient was presented with severe bilateral ocular discharge, and from both eyes, dipterous fly larvae were extracted. The dog was given symptomatic treatment (deworming, topical and systemic antibiotics, nutritional support) but never regained a normal eye appearance. At the time of the initial presentation, it had severe vision impairment because of bilateral cicatricial symblepharon, total in the left eye and occupying 3/4 of the cornea in the right eye. Surgery was proposed to attempt a resolution. Superficial keratectomy was performed in both eyes. After a midline incision in the cornea, the conjunctiva was dissected away. The conjunctiva was apposed to and sutured to the limbus and secured in the upper and lower conjunctival fornix. Additionally, in the left eye, a lateral canthotomy and canthoplasty were performed to enlarge the size of the eyelid opening. The corneal epithelium healed without complications, the patient regained vision, and after 36 months of follow-up, no recurrences were observed. To the authors' knowledge, this is the first report of symblepharon secondary to ophthalmomyiasis externa in a dog. PMID- 22050789 TI - Long-pulsed Nd : YAG laser: does it give clinical benefit on the treatment of resistant telangiectasia? AB - BACKGROUND: Long-pulsed Nd : YAG laser has been used in treating larger and deep seated leg veins. OBJECTIVE: This study investigated the effectiveness and safety of long-pulsed Nd : YAG laser to treat alae nasae and nasal tip telangiectasia. METHODS: Twelve patients were evaluated in a prospective IRB approved study. They had a history of previous unsatisfactory treatments with pulsed dye laser and/or intense pulsed light for their telangiectases on alae nasae and tip (4-12 times, average 5.8 times). All patients underwent a single treatment session using long pulsed Nd : YAG laser. Photographic images were taken. At 12-week follow-up, two independent physicians evaluated the percentage of vessels cleared, and patients were asked to rate their satisfaction with the procedure. RESULTS: Five men and seven women were enrolled (aged 43 +/- 5.8 years). Total clearance of vessels was 78.3%. The number of vessels in diameter of 0.1 mm was reduced by 61.1% and that of vessels in diameter of 0.2-0.3 mm decreased by 92.2% on the average at 12-week follow-up. Eleven of 12 patients were very satisfied with the clinical results. One patient rated as 'satisfied' due to hyperpigmentation after the treatment, which improved at 12-week follow-up. CONCLUSION: Long-pulsed Nd : YAG laser can be considered as another effective and safe treatment modality for stubborn telangeictasia even on face, if applied cautiously. PMID- 22050791 TI - Iodine-mediated cascade cyclization of enediynes to iodinated benzo[a]carbazoles. AB - Treatment of N,N-dimethyl 2-[2-(2-ethynylphenyl)ethynyl]anilines (1) with 1.2 equiv of iodine in CH(2)Cl(2) gave benzo[a]carbazoles (2) in good yields. Mechanistic studies showed this reaction must go through the haloindole (3) followed by iodonium ion catalyzed atom-transfer cyclization reaction to give the benzo[a]carbazoles. PMID- 22050792 TI - Quantity recognition among speakers of an anumeric language. AB - Recent research has suggested that the Piraha, an Amazonian tribe with a number less language, are able to match quantities > 3 if the matching task does not require recall or spatial transposition. This finding contravenes previous work among the Piraha. In this study, we re-tested the Pirahas' performance in the crucial one-to-one matching task utilized in the two previous studies on their numerical cognition, as well as in control tasks requiring recall and mental transposition. We also conducted a novel quantity recognition task. Speakers were unable to consistently match quantities > 3, even when no recall or transposition was involved. We provide a plausible motivation for the disparate results previously obtained among the Piraha. Our findings are consistent with the suggestion that the exact recognition of quantities > 3 requires number terminology. PMID- 22050790 TI - Inhibition of JAK2/STAT3 signalling induces colorectal cancer cell apoptosis via mitochondrial pathway. AB - Abnormalities in the JAK2/STAT3 pathway are involved in the pathogenesis of colorectal cancer (CRC), including apoptosis. However, the exact mechanism by which dysregulated JAK2/STAT3 signalling contributes to the apoptosis has not been clarified. To investigate the role of both JAK2 and STAT3 in the mechanism underlying CRC apoptosis, we inhibited JAK2 with AG490 and depleted STAT3 with a small interfering RNA. Our data showed that inhibition of JAK2/STAT3 signalling induced CRC cellular apoptosis via modulating the Bcl-2 gene family, promoting the loss of mitochondrial transmembrane potential (Deltapsim) and the increase of reactive oxygen species. In addition, our results demonstrated that the translocation of cytochrome c (Cyt c), caspase activation and cleavage of poly (ADP-ribose) polymerase (PARP) were present in apoptotic CRC cells after down regulation of JAK2/STAT3 signalling. Moreover, inhibition of JAK2/STAT3 signalling suppressed CRC xenograft tumour growth. We found that JAK2/STAT3 target genes were decreased; meanwhile caspase cascade was activated in xenograft tumours. Our findings illustrated the biological significance of JAK2/STAT3 signalling in CRC apoptosis, and provided novel evidence that inhibition of JAK2/STAT3 induced apoptosis via the mitochondrial apoptotic pathway. Therefore, JAK2/STAT3 signalling may be a potential target for therapy of CRC. PMID- 22050793 TI - Gas-generating polymeric microspheres for long-term and continuous in vivo ultrasound imaging. AB - Ultrasound (US) imaging is one of the most common biomedical imaging methods, due to the easy assessment and noninvasive way. For more precise and accurate US imaging, many contrast agents have been developed in a form of microbubbles composed of inner gas and shell materials. However, microbubbles showed undesirable short half-life under acoustic field during US imaging and insufficient in vivo stability in blood flow due to diffusion or bubble destruction. Therefore, the improvement of the half-life and stability of microbubbles under in vivo condition is highly needed for long-term in vivo US imaging. Herein, we developed rationally designed gas-generating polymeric microsphere (GGPM) that can produce microbubbles without encapsulation of gas for long-term and continuous US imaging. The poly(cholesteryl gamma-butyrolactone-b propylene oxide), poly(CB-PO), with carbonate side chains was synthesized as gas generating polymer by ring-opening polymerization of cholestryl gamma butyrolactone (CB) and propylene oxide (PO). As optimal structure for intense US signal generation, porous GGPMs (p-GGPMs) with the average size about 3-5 MUm were prepared with poly(CB-PO) by double emulsion method. These p-GGPMs generated continuous US signals over 70 min, while the signals from Sonovue((r)), a commercial US contrast agent were completely attenuated within 15 min. This long term signal duration of p-GGPM was also reproduced when they were subcutaneously injected under the skin of mouse. Moreover, as advanced in vivo application, the fine US imaging of heart in rat was enabled by intravenous injection of p-GGPM. Therefore, these overall results showed the great potential of p-GGPM as gas generating US contrast agent for in vivo biomedical imaging and diagnosis. PMID- 22050794 TI - Epidural anesthesia as a novel anesthetic technique for anterior lumbar interbody fusion. AB - STUDY OBJECTIVE: To determine if epidural anesthesia is a reasonable technique for anterior lumbar interbody fusion. DESIGN: Retrospective chart review. SETTING: Academic university hospital. MEASUREMENTS: The charts of patients who underwent an anterior lumbar interbody fusion between January 1, 2001 and November 1, 2008 were reviewed. A total of 102 consecutive patients, of whom 19 received an epidural and 83 underwent general anesthesia, met inclusion criteria. Postoperative pain, nausea, opioid administration, operating room time, anesthesia time, Postanesthesia Care Unit (PACU) time, and total hospital time were compared. MAIN RESULTS: In the PACU, patients receiving epidural anesthesia showed reductions in median immediate [numerical rating scale (NRS) 0 vs 7; P < 0.001] and peak (NRS 4 vs 8; P = 0.001) postoperative pain scores, and postoperative mean arterial pressure (69.7 vs 90.3; P < 0.001). Epidural anesthesia patients also needed significantly less intravenous morphine equivalent medication both intraoperatively (5 vs 29; P < 0.001) and postoperatively (3.34 vs 10; P = 0.021). CONCLUSIONS: Epidural anesthesia for anterior lumbar interbody fusion is potentially beneficial compared with general anesthesia, showing improved perioperative pain control. PMID- 22050795 TI - The effects of hormonal status on upper airway patency in normal female subjects during propofol anesthesia. AB - STUDY OBJECTIVE: To determine the mechanical upper airway properties and compensatory neuromuscular responses to obstruction during propofol anesthesia in the follicular and luteal phases of the menstrual cycle. DESIGN: Prospective, randomized study. SETTING: University-affiliated hospital. SUBJECTS: 12 premenopausal female volunteers for studies of upper airway collapse throughout their menstrual cycle during the follicular phase (6 -10 days) and mid-late luteal phase (20 - 24 days). MEASUREMENTS: The level of propofol anesthesia (1.5 2.0 MUg/mL) required to suppress arousal responses was determined by Observer's Assessment of Alertness/Sedation scoring (level 2) and confirmed by bispectral index monitoring. Pressure-flow relationships were constructed to evaluate collapsibility (P(CRIT)) and up-stream resistance (R(US)) during acute [Passive; hypotonic electromyography (EMG)] and sustained (Active; elevated EMG) changes in nasal mask pressure. The difference between passive P(CRIT) and active P(CRIT) (DeltaP(CRIT A-P)) represented the magnitude of the compensatory response to obstruction. MAIN RESULTS: Passive P(CRIT) was significantly higher in the mid late luteal phase (-4.7 cm H(2)O) than in the follicular phase (-6.2 cmH(2)O; P < 0.05). Active P(CRIT) significantly decreased compared with passive P(CRIT) in the follicular phase (-10.1 cm H(2)O) and in the mid-late luteal phase (-7.7 cm H(2)O) and (P < 0.05). No significant difference was noted in DeltaP(CRIT) between the follicular (3.9 +/- 2.9 cm H(2)O) and mid-late luteal phases (3.0 +/- 2.6 cm H(2)O). No differences were seen in R(US) between the menstrual phases for either the passive (P = 0.8) or active (P = 0.75) states. CONCLUSIONS: Menstrual phase has an effect on anatomical alterations (mechanical properties) in the hypotonic upper airway during propofol anesthesia. PMID- 22050796 TI - Rapid injection of propofol reduces vascular pain and facilitates Laryngeal Mask Airway insertion. AB - STUDY OBJECTIVE: To compare the clinical efficacy of a rapid injection of propofol in regard to pain and ability to facilitate Laryngeal Mask Airway (LMA) insertion. DESIGN: Randomized, single-blinded, placebo-controlled study. SETTING: University hospital. PATIENTS: 120 ASA physical status 1 and 2 patients undergoing elective orthopedic surgeries. INTERVENTIONS: Patients were randomly allocated to one of 4 groups. Group A patients were pretreated with normal saline followed by propofol 2.0 mg/kg at 3.3 mg/sec. Group B patients were pretreated with lidocaine 0.5 mg/kg followed by propofol 2.0 mg/kg at 3.3 mg/sec. In Group C, patients were pretreated with lidocaine 1.0 mg/kg followed by propofol 2.0 mg/kg at 3.3 mg/sec. In Group D, patients were pretreated with normal saline followed by propofol 2.0 mg/kg at 50 mg/sec. MEASUREMENTS: Pain on injection was measured using a 4-point scale. Scale and success rate of smooth LMA insertion also were recorded. MAIN RESULTS: Rapid injection was less painful than after pretreatment with lidocaine 0.5 mg/kg, but was similar to slow injection after pretreatment with lidocaine 1.0 mg/kg. Rapid injection facilitated LMA insertion, unlike slow injection with lidocaine 0.5 mg/kg pretreatment, and was similarly successful to slow injection after pretreatment with lidocaine 1.0 mg/kg. CONCLUSIONS: The rapid administration of propofol reduces pain and facilitates LMA insertion versus slow administration of propofol. PMID- 22050797 TI - Effects of preoperative oral beta blocker versus intraoperative nitroprusside or esmolol on quality of surgical field during tympanoplasty. AB - STUDY OBJECTIVE: To determine whether orally administered atenolol provides an optimal surgical field in comparison to intravenous sodium nitroprusside or esmolol during tympanoplasty. DESIGN: Randomized, double-blinded study. SETTING: Operating room in a university hospital. PATIENTS: 105 ASA physical status 1 and 2 adult patients undergoing tympanoplasty. INTERVENTIONS: Patients were randomized to three groups to receive either oral atenolol 50 mg twice daily for one day prior to surgery (Group I), intraoperative nitroprusside infusion (Group II), or intraoperative esmolol infusion (Group III). MEASUREMENTS: Quality of the operative field, mean arterial pressure, and heart rate were assessed. Blood gases, liver enzymes, cardiac troponin I, creatine kinase isoenzyme-MB release, blood urea nitrogen, and creatinine concentrations also were measured. MAIN RESULTS: Time to achieve target surgical field was significantly reduced in the atenolol group versus the other groups (8.3 +/- 3.2, 28.2 +/- 6.4, and 17.2 +/- 5.3 min, respectively). Heart rate significantly decreased in the atenolol and esmolol groups versus the nitroprusside group (P < 0.0001). Mean arterial pressure after extubation and frequency of rebound hypertension were comparable in the groups. No significant changes in cardiac enzymes, renal and hepatic function, or acid-base status were noted. CONCLUSIONS: Although the three drugs are acceptable for obtaining an optimum surgical field, preoperative oral beta blocker appeared to be rapid in onset and was simpler to implement. PMID- 22050798 TI - A prospective controlled study to determine the blood propofol concentration in anesthesiologists exposed to propofol vapor in the expired gases of patients receiving propofol-based intravenous sedation. AB - STUDY OBJECTIVE: To determine the blood propofol concentration of anesthesiologists who were exposed to the expired gases of patients receiving propofol-based intravenous (IV) sedation. DESIGN: Prospective controlled investigation and laboratory analysis. SETTING: Operating room of a university hospital and an independent technical laboratory. SUBJECTS: 5 anesthesiologists who independently delivered propofol-based IV sedation to patients presenting for first trimester termination of pregnancy. In addition, a patient receiving propofol-based IV sedation was recruited as a positive control. A laboratory technician who never had previous exposure to propofol was recruited as a negative control. INTERVENTIONS: Blood samples were obtained from each anesthesiologist before and after an 8-hour work period of anesthesia care of patients as described above. Blood samples were also obtained from the positive control, following propofol-based IV sedation, and the negative control. MEASUREMENTS: An independent laboratory determined the blood propofol concentrations using a gas-liquid partition chromatograph and verified the results by repeated measurements in order to avoid a laboratory error. The gas liquid partition chromatograph had an analytic capability that set the detection limit for propofol at 50 ng/mL. MAIN RESULTS: None of the anesthesiologists had detectable blood propofol concentration in either the pre-exposure or post exposure sample. The positive control and the negative control had detectable and non-detectable blood propofol concentration, respectively. CONCLUSIONS: This experiment did not detect propofol in the blood of anesthesiologists who administered propofol-based IV sedation to patients. PMID- 22050799 TI - Exposure of anesthesia providers in recovery from substance abuse to potential triggering agents. AB - STUDY OBJECTIVE: To determine the experience, attitudes, and opinions of anesthesia providers in recovery from addiction to anesthetic agents, who subsequently undergo surgery or who require opioid analgesics for injuries or other conditions. DESIGN: Survey instrument. SETTING: Academic medical center. SUBJECTS: Physicians and nurse-anesthetists in recovery in the United States. MEASUREMENTS: A link to a survey was posted on the Anesthetists in Recovery website on January 17, 2010 and allowed to remain active for a period of one week. The survey also was distributed via email to recovering anesthesiologists in a "snowball sampling" method. Completed surveys were reviewed, and data were compiled using Survey Monkey, with categorical variables described as frequencies and percentages. MAIN RESULTS: A total of 30 surveys were returned, with 27 (90%) reporting a history of abusing anesthetics or drugs commonly found in the work environment, and 19 (65.5%) reporting abuse of recreational drugs and drugs used during the administration of anesthesia. Twenty-eight (93%) respondents reported finding themselves in a situation that necessitated they receive their former drug of choice for legitimate medical reasons while in recovery. CONCLUSIONS: Anesthesia care providers in recovery from addiction to anesthetic agents may undergo subsequent exposure to these agents due to medical necessity. Participation in a program of recovery with support from family members may decrease the risk of relapse but does not eliminate it. PMID- 22050800 TI - Fibrodysplasia ossificans progressiva: anesthetic management in complex orthopedic spine procedures. AB - Fibrodysplasia ossificans progressiva (FOP) is a rare disorder of the connective tissue leading to progressive tissue ossification and immobilization. Soft-tissue trauma may exacerbate this condition, causing further ossification. Multisystem involvement includes restrictive lung disease, cervical ankylosis with limited mouth opening, and cardiac dysfunction. A 39-year-old woman with FOP presented with multiple orthopedic spine and femur fractures sustained from a fall. Anesthetic management was complicated by airway, pulmonary, and positioning challenges. Neuromonitoring allowed identification of spinal cord ischemia while avoiding a wake-up test. PMID- 22050801 TI - Intracranial hemorrhage from undiagnosed metastatic brain tumor during general anesthesia. AB - A patient with endometrial cancer presented with intracranial hemorrhage from an undiagnosed metastatic brain tumor during abdominal radical hysterectomy. Since she was neurologically intact, a systematic examination for brain metastasis had not been performed preoperatively. After the surgery, she had delayed recovery from general anesthesia with right hemiplegia and aphasia. Computed tomography and magnetic resonance imaging showed left putaminal hemorrhage from brain metastasis. PMID- 22050802 TI - Acute hyperkalemia as a complication of intravenous therapy with epsilon aminocaproic acid. AB - Epsilon-aminocaproic acid (EACA) is used frequently during surgery as prophylaxis to decrease blood loss and transfusion requirements. A rare complication of EACA induced acute hyperkalemia in a patient undergoing total hip replacement is presented. PMID- 22050803 TI - A new risk of facemask ventilation: entrained esophageal air. AB - Facemask ventilation has been associated with the development of postoperative nausea and vomiting, increasing the risk of tracheal aspiration; development of gastric distension that further impairs alveolar ventilation; perforation of gastric and duodenal ulcers; development of pneumothorax; extrabronchial air dissection; and development of cardiac dysrhythmias, including bradycardia from indirect vagal nerve stimulation. An unusual complication that occurred during prolonged facemask ventilation is presented: development of a pseudo-obstruction of the intrathoracic airway due to the presence of entrained esophageal air. PMID- 22050804 TI - Transhiatal herniation of intestine with circulatory collapse on anesthesia induction. AB - Diaphragmatic herniation is known to create cardiorespiratory challenges for the anesthesiologist. With the increasing use of the transhiatal surgical approach for esophagectomy, the occurrence of transhiatal herniation of bowel is likely to be encountered. A case of circulatory collapse during induction of anesthesia in a patient with transhiatal herniation is presented. PMID- 22050805 TI - Perioperative evaluation of the obese patient. AB - There is rapidly increasing prevalence of obesity throughout Western societies and increasing numbers of patients undergoing surgery are obese. Obesity is a condition of chronic systemic inflammation and is associated with an increased burden of comorbidities. Despite traditional teaching, obesity may not be an independent risk factor for poor postoperative outcomes. The Obesity Paradox describes the observation that small amounts of excess body fat may be protective against postoperative complications. PMID- 22050806 TI - Regional anesthesia in anticoagulated patients. PMID- 22050808 TI - Premolar loss following insertion of a Classic Laryngeal Mask Airway in a patient in the prone position. PMID- 22050809 TI - "Full stomach" in a diabetic patient taking anticholinergics after 12 hours of fasting. PMID- 22050810 TI - Subarachnoid-pleural fistula complicating thoracotomy. PMID- 22050811 TI - Audit of recall of propofol injection pain. PMID- 22050812 TI - Postpartum analgesia with dexmedetomidine in opioid tolerance during pregnancy. PMID- 22050813 TI - Precipitation of sugammadex by protamine. PMID- 22050814 TI - Hemodynamic, respiratory, and fluid volume changes with bronchopulmonary lavage. PMID- 22050815 TI - Korean translation and use of the Iowa Satisfaction with Anesthesia Scale. PMID- 22050816 TI - Neck flexion to correct the placement of a malplaced Laryngeal Mask Airway (LMA) Supreme. PMID- 22050817 TI - Urinary retention during trial of a spinal cord stimulator. PMID- 22050818 TI - Limited mouth opening following induction of anesthesia in two patients with masticatory muscle tendon-aponeurosis hyperplasia. PMID- 22050819 TI - Thrombelastograph platelet mapping in a patient with von Willebrand disease who was treated with Humate-P. PMID- 22050820 TI - Phage therapy pharmacology: calculating phage dosing. AB - Phage therapy, which can be described as a phage-mediated biocontrol of bacteria (or, simply, biocontrol), is the application of bacterial viruses-also bacteriophages or phages-to reduce densities of nuisance or pathogenic bacteria. Predictive calculations for phage therapy dosing should be useful toward rational development of therapeutic as well as biocontrol products. Here, I consider the theoretical basis of a number of concepts relevant to phage dosing for phage therapy including minimum inhibitory concentration (but also "inundation threshold"), minimum bactericidal concentration (but also "clearance threshold"), decimal reduction time (D value), time until bacterial eradication, threshold bacterial density necessary to support phage population growth ("proliferation threshold"), and bacterial density supporting half-maximal phage population growth rates (K(B)). I also address the concepts of phage killing titers, multiplicity of infection, and phage peak densities. Though many of the presented ideas are not unique to this chapter, I nonetheless provide variations on derivations and resulting formulae, plus as appropriate discuss relative importance. The overriding goal is to present a variety of calculations that are useful toward phage therapy dosing so that they may be found in one location and presented in a manner that allows facile appreciation, comparison, and implementation. The importance of phage density as a key determinant of the phage potential to eradicate bacterial targets is stressed throughout the chapter. PMID- 22050821 TI - From Rio Tinto to Mars: the terrestrial and extraterrestrial ecology of acidophiles. AB - The recent geomicrobiological characterization of Rio Tinto, Iberian Pyrite Belt (IPB), has proven the importance of the iron cycle, not only in generating the extreme conditions of the habitat (low pH, high concentration of toxic heavy metals) but also in maintaining the high level of microbial diversity, both prokaryotic and eukaryotic, detected in the water column and the sediments. The extreme conditions of the Tinto basin are not the product of industrial contamination but the consequence of the presence of an underground bioreactor that obtains its energy from the massive sulfide minerals of the IPB. To test this hypothesis, a drilling project was carried out to intersect ground waters that interact with the mineral ore in order to provide evidence of subsurface microbial activities and the potential resources to support these activities. The oxidants that drive the system appear to come from the rock matrix, contradicting conventional acid mine drainage models. These resources need only groundwater to launch microbial metabolism. There are several similarities between the vast deposits of sulfates and iron oxides on Mars and the main sulfide-containing iron bioleaching products found in the Tinto. Firstly, the short-lived methane detected both in Mars' atmosphere and in the sediments and subsurface of the IPB and secondly, the abundance of iron, common to both. The physicochemical properties of iron make it a source of energy, a shield against radiation and oxidative stress as well as a natural pH controller. These similarities have led to Rio Tinto's status as a Mars terrestrial analogue. PMID- 22050822 TI - Fungal adaptation to extremely high salt concentrations. AB - Hypersaline environments support substantial microbial communities of selected halotolerant and halophilic organisms, including fungi from various orders. In hypersaline water of solar salterns, the black yeast Hortaea werneckii is by far the most successful fungal representative. It has an outstanding ability to overcome the turgor loss and sodium toxicity that are typical for hypersaline environments, which facilitates its growth even in solutions that are almost saturated with NaCl. We propose a model of cellular responses to high salt concentrations that integrates the current knowledge of H. werneckii adaptations. The negative impact of a hyperosmolar environment is counteracted by an increase in the energy supply that is needed to drive the energy-demanding export of ions and synthesis of compatible solutes. Changes in membrane lipid composition and cell-wall structure maintain the integrity and functioning of the stressed cells. Understanding the salt responses of H. werneckii and other fungi (e.g., the halophilic Wallemia ichthyophaga) will extend our knowledge of fungal stress tolerance and promote the use of the currently unexploited biotechnological potential of fungi that live in hypersaline environments. PMID- 22050823 TI - Resistance of yeasts to weak organic acid food preservatives. AB - Carboxylate weak acids are invaluable for large-scale food and beverage preservation. However, in response to safety concerns, there is now desire to reduce the use of these additives. The resistance to these compounds displayed by spoilage yeasts and fungi is a major reason why these preservatives often have to be used in millimolar levels. This chapter summarizes the mechanisms whereby yeasts are rendered resistant to acetate, propionate, sorbate, and benzoate. In baker's yeast (Saccharomyces cerevisiae), resistance to high acetic acid is acquired partly by loss of the plasma membrane aquaglyceroporin that facilitates the passive diffusional entry of undissociated acid into cells (Fps1), and partly through a transcriptional response mediated by the transcription factor Haa1. Other carboxylate preservatives are too large to enter cells through the Fps1 channel but instead penetrate at appreciable rates by passive diffusion across the plasma membrane. In Saccharomyces and Candida albicans though not, it seems, in the Zygosaccharomyces, resistance to the latter acids involves activation of the War1 transcription factor, which in turn generates strong induction of a specific plasma membrane ATP-binding cassette transporter (Pdr12). The latter actively pumps the preservative anion from the cell. Other contributors to weak acid resistance include enzymes that allow preservative degradation, members of the Tpo family of major facilitator superfamily transporters, and changes to the cell envelope that minimize the diffusional entry of the preservative into the cell. PMID- 22050824 TI - Silver nanoparticles: a microbial perspective. AB - Silver nanoparticles (NPs) are used for a wide range of commercial reasons to restrict microbial growth. The increasing use of silver NPs in modern materials ensures they will find their way into environmental systems. The mode of action which makes them desirable as an antimicrobial tool could also pose a severe threat to the natural microbial balance existing in these systems. Research into the potential environmental threats of silver NPs has mainly focused on particular areas, such as their influence in rivers and estuaries or their effect on organisms such as earthworms and plants. There is a need to focus studies on all aspects of the microbial world and to highlight potential risks and methods of overcoming problems before significant damage is done. This review focuses on the antimicrobial uses, mechanisms of toxicity, and effects on the environment (mainly soil) of silver NPs, illustrating gaps in current knowledge. PMID- 22050825 TI - ADAMTS17 mutation associated with primary lens luxation is widespread among breeds. AB - Primary lens luxation (PLL) is a well-recognized, painful and potentially blinding inherited ocular condition in dogs. We screened PLL-affected dogs of 30 different breeds, to identify those which carried a previously described c.1473+1 G>A mutation in ADAMTS17 that is associated with PLL in Miniature Bull terriers, Lancashire Heelers, and Jack Russell terriers. This ADAMTS17 mutation was identified in PLL-affected dogs from 14 additional breeds. PLL-affected dogs from some breeds (most notably the Shar pei and the Brittany spaniel) did not carry the G1473+1A ADAMTS17 mutation, indicating they must suffer from a genetically distinct form of the condition. We also estimated the frequency of this ADAMTS17 mutation in some of the breeds. Our findings indicate the mutation segregates in a large number of different breeds of dog, many of which are terriers or breeds with terrier co-ancestry, but some of which have more diverse origins. Our results also indicate that the mutation is present at high frequency within most of the breeds in which it segregates. In the miniature bull terrier breed estimates of mutation frequency ranged from 0.27 to 0.39, corresponding to 7.3 15.2% PLL-affected dogs in this breed. We also identified an increased risk of PLL associated with heterozygosity at ADAMTS17, suggesting that carriers carry a low risk of developing PLL. PMID- 22050826 TI - The bladder pain/interstitial cystitis symptom score: development, validation, and identification of a cut score. AB - BACKGROUND: There is a need to develop a self-report measure that reliably identifies moderate to severe bladder pain syndrome (BPS) patients for inclusion into clinical trials to assess the efficacy of new BPS treatments. OBJECTIVE: To develop and validate a patient-reported symptom-based instrument, the Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS), for clinical trial eligibility of BPS patients. DESIGN, SETTING, AND PARTICIPANTS: Stage 1: Qualitative concept elicitation (CE) interviews were conducted with BPS patients in France (n=12), Germany (n=12), and the United States (US) (n=20), and overactive bladder (OAB) (n=10) patients in the US for comparison. Stage 2: Cognitive debriefing (CD) interviews were performed with US BPS patients (n=20). Stage 3: An observational study with 99 BPS, 99 OAB, and 100 healthy participants in the US was used to perform item reduction, identify cut scores, and validate the measure. A cut score was defined using logistic regression and receiver operating characteristic curves. Psychometric properties, including test-retest reliability, were assessed. MEASUREMENTS: In addition to the BPIC-SS, the Pelvic Pain and Urgency/Frequency Patient Symptom Scale, the Interstitial Cystitis Symptom Index, a Clinician Global Impression of Severity, and a Patient Global Impression of Change were included in the observational study. RESULTS AND LIMITATIONS: In CE, reported symptoms were bladder pain, persistent urge to urinate, and high urinary frequency. In CD, 13 items were deleted, and 15 were retained. Based on validation analyses, qualitative findings, and clinical relevance, the instrument was reduced to eight items that had strong sensitivity (0.72) and specificity (0.86) with a cut score >=19 to determine clinical trial inclusion. Psychometric properties were strong. CONCLUSIONS: The BPIC-SS is a reliable, valid, and appropriate questionnaire to select BPS/interstitial cystitis patients for clinical trials. PMID- 22050827 TI - Effects of 28 days of resistance exercise while consuming commercially available pre- and post-workout supplements, NO-Shotgun(r) and NO-Synthesize(r) on body composition, muscle strength and mass, markers of protein synthesis, and clinical safety markers in males. AB - PURPOSE: The effects of 28 days of heavy resistance training while ingesting the pre- and post-workout supplements, NO-Shotgun(r) and NO-Synthesize(r) were determined on body composition, muscle strength and mass, markers of protein synthesis, and clinical safety markers. METHODS: Nineteen non-resistance-trained males participated in a resistance training program 4 times/week for 28 days while either ingesting 27 g/day of carbohydrate (CARB) or NO-Shotgun(r) 30 min pre-exercise and 27 g/day of carbohydrate or NO- Synthesize(r) 30 min post exercise (NOSS). Data were analyzed with separate 2 * 2 ANOVA (p < 0.05). RESULTS: Total body mass was increased in both groups (p = 0.001), but not different between groups. Fat mass was unchanged with CARB, but NOSS decreased fat mass (p = 0.026). Both groups increased fat-free mass (p = 0.001); however, the increases were greater with NOSS (p = 0.023). NOSS underwent greater increases in upper-body (p = 0.023) and lower-body (p = 0.035) strength than CARB. Myofibrillar protein significantly increased in both groups (p = 0.041), with NOSS being greater than CARB (p = 0.049). All of the MHC isoforms were significantly increased in both groups; however, NOSS was greater than CARB for MHC 1 (p = 0.013) and MHC 2A (p = 0.046). All of the myogenic regulatory factors were significantly increased in both groups; however, NOSS was greater than CARB for Myo-D (p = 0.038) and MRF-4 (p = 0.001). For the whole blood and serum clinical chemistry markers, all variables remained within normal clinical ranges. CONCLUSIONS: Heavy resistance training for 28 days, with NO-Shotgun(r) and NO Synthesize(r) ingested before and after exercise, respectively, significantly improved body composition and increased muscle mass and performance without abnormally impacting any of the clinical chemistry markers. PMID- 22050829 TI - Observations on the ultrastructure of equatorial scleral collagen fibrils in sheep eyes. AB - OBJECTIVE: To investigate collagen fibrils of the equatorial sclera in relation to the age-related changes in eye size in sheep. ANIMALS STUDIED: Lambs and outbred ewes. PROCEDURES: Sheep eyes (three lamb and three from adult outbred ewes), presumed disease-free, were processed for transmission electron microscopy (TEM) immediately postmortem. Tissue blocks from the equatorial region were sectioned across fibril bundles orientated along the equator. Micrographs including at least 500 fibrils were projected at 22,000* magnification for measures of fibril diameters (FDs). RESULTS: Lamb eyes were smaller than those of adult ewes but equatorial scleral thickness was only marginally less at 0.232+/ 0.013 vs. 0.254+/-0.012 mm (P value not significant). Scleral tissue was composed of compacted bundles of collagen fibers that tended to be rounder in outer compared to being flatter in inner regions. In typical (normal) appearing regions, FDs were distinctly larger (68-410 nm) in outer sclera compared to inner sclera (63-281 nm). Outer sclera FDs were bimodal averaging 192+/-58 nm, compared to unimodal distributions at inner locations averaging 156+/-48 nm (P<0.001). Some atypical regions, especially at outer-mid sclera locations, were also noted where the FD distribution was bimodal but also included numerous microfibrils (<50 nm diameter), with similar appearances being found for both lamb and adult ewe eyes. CONCLUSIONS: The equatorial sclera is a mixture of rounder versus flatter collagen fiber bundles, the former being more likely to be made up of a mixture of both smaller and larger fibrils, as compared to slightly smaller fibrils. PMID- 22050828 TI - Not so benign haematology: anaemia of the elderly. AB - Developed countries, such as the United Kingdom, are experiencing a change in demographics resulting in the largest proportion of adults over 65 years of age that our health systems have ever experienced. As such, haematologists must be prepared to evaluate and treat anaemia in a more complicated patient population, but sufficient evidence-based guidelines are lacking. Critical next steps that must be taken to ensure the best care of this population include the determination of appropriate haemoglobin concentrations for older adults in light of age, gender, race, and comorbidities; the development of interventional trials that address physical performance outcomes in addition to haemoglobin targets; and translational studies which address the molecular pathogenesis of anaemia in older adults with the most advanced scientific approaches. PMID- 22050830 TI - Suitability of measures of self-reported medication adherence for routine clinical use: a systematic review. AB - BACKGROUND: There is a recognised need to build primary care medication adherence services which are tailored to patients' needs. Continuous quality improvement of such services requires a regular working method of measuring adherence in order to monitor effectiveness. Self report has been considered the method of choice for clinical use; it is cheap, relatively unobtrusive and able to distinguish between intentional and unintentional non-adherence, which have different underlying causes and therefore require different interventions. A self report adherence measure used in routine clinical practice would ideally be brief, acceptable to patients, valid, reliable, have the ability to distinguish between different types of non-adherence and be able to be completed by or in conjunction with carers where necessary. METHODS: We systematically reviewed the literature in order to identify self report adherence measures currently available which are suitable for primary care and evaluate the extent to which they met the criteria described above. We searched the databases Medline, Embase, International Pharmaceutical Abstracts, Pharmline, CINAHL, PsycINFO and HaPI to identify studies reporting the development, validation or reliability of generic adherence measures. One reviewer screened all abstracts and assessed all relevant full text articles obtained and a second reviewer screened/assessed 10% to check reliability. RESULTS: Fifty eight measures were identified. While validation data were presented in support of the vast majority of self reported measures (54/58), data for a relatively small number of measures was presented for reliability (16/58) and time to complete (3/58). Few were designed to have the ability to be completed by or in conjunction with carers and few were able to distinguish between different types of non-adherence, which limited their ability be used effectively in the continuous improvement of targeted adherence enhancing interventions. The data available suggested that patients find it easier to estimate general adherence than to report a specific number of doses missed. Visual analogue scales can be easier for patients than other types of scale but are not suitable for telephone administration. CONCLUSIONS: There is a need for a measure which can be used in the routine continual quality monitoring of adherence services. PMID- 22050831 TI - Diagnostic challenges of Marfan syndrome in an XYY young man. AB - Tall stature is a common feature of both Marfan syndrome and XYY syndrome. Differential diagnosis between these entities has important prognostic implications. We report the case of a 21-year-old young man with a previously known diagnosis of XYY syndrome, in whom the identification of a fibrilin-1 mutation was determinant to establish an appropriate diagnosis, medical follow up, and genetic counselling. PMID- 22050832 TI - Pharmaceutical services for endemic situations in the Brazilian Amazon: organization of services and prescribing practices for Plasmodium vivax and Plasmodium falciparum non-complicated malaria in high-risk municipalities. AB - BACKGROUND: In spite of the fact that pharmaceutical services are an essential component of all malaria programmes, quality of these services has been little explored in the literature. This study presents the first results of the application of an evaluation model of pharmaceutical services in high-risk municipalities of the Amazon region, focusing on indicators regarding organization of services and prescribing according to national guidelines. METHODS: A theoretical framework of pharmaceutical services for non-complicated malaria was built based on the Rapid Evaluation Method (WHO). The framework included organization of services and prescribing, among other activities. The study was carried out in 15 primary health facilities in six high-risk municipalities of the Brazilian Amazon. Malaria individuals >= 15 years old were approached and data was collected using specific instruments. Data was checked by independent reviewers and fed to a data bank through double-entry. Descriptive variables were analyzed. RESULTS: A copy of the official treatment guideline was found in 80% of the facilities; 67% presented an environment for receiving and prescribing patients. Re-supply of stocks followed a different timeline; no facilities adhered to forecasting methods for stock management. No shortages or expired anti-malarials were observed, but overstock was a common finding. On 86.7% of facilities, the average of good storage practices was 48%. Time between diagnosis and treatment was zero days. Of 601 patients interviewed, 453 were diagnosed for Plasmodium vivax; of these, 99.3% received indications for the first-line scheme. Different therapeutic schemes were given to Plasmodium falciparum patients. Twenty-eight (4.6%) out of 601 were prescribed regimens not listed in the national guideline. Only 5.7% individuals received a prescription or a written instruction of any kind. CONCLUSIONS: The results show that while diagnostic procedure is well established and functioning in the Brazilian malaria programme, prescribing is still an activity that is actually not performed. The absence of physicians and poor integration between malaria services and primary health services make for the lack of a prescription or written instruction for malaria patients throughout the Brazilian Amazon. This fact may lead to a great number of problems in rational use and in adherence to medication. PMID- 22050833 TI - Biological pathways to adaptability--interactions between genome, epigenome, nervous system and environment for adaptive behavior. AB - Because living systems depend on their environment, the evolution of environmental adaptability is inseparable from the evolution of life itself (Pross 2003). In animals and humans, environmental adaptability extends further to adaptive behavior. It has recently emerged that individual adaptability depends on the interaction of adaptation mechanisms at diverse functional levels. This interaction enables the integration of genetic, epigenetic and environmental factors for coordinated regulation of adaptations. In this review, we first present the basis for the regulation of adaptation mechanisms across functional levels. We then focus on neuronal activity-regulated adaptation mechanisms that involve the regulation of genes, noncoding DNA (ncDNA), ncRNAs and proteins to change the structural and functional properties of neurons. Finally, we discuss a selection of these important neuronal activity-regulated molecules and their effects on brain structure and function and on behavior. Most of the evidence so far is based on sampling of animal tissue or post-mortem studies in humans. However, we also present techniques that combine genetic with behavioral and neurophysiological measures in humans (e.g. genetic imaging) and discuss their potential and limitations. We argue that we need to understand how neuronal activity-dependent adaptation mechanisms integrate genetic, epigenetic and experience-dependent signals in order to explain individual variations in behavior and cognitive performance. PMID- 22050834 TI - [Reliability of the pulse contour analysis for cardiac output measurement for assessing the fluid responsiveness]. AB - BACKGROUND: The cardiac output (CO) is classically measured in intensive care unit patients. pulse contour (PC) method allows monitoring of CO. OBJECTIVE: The aim of the present study was to assess the ability of PC to assess the fluid responsiveness defined as an increase in CO more than or equal to 15% after 500 mL hydroxyethyl starch over 20 minutes. PATIENTS AND METHODS: In this observational prospective study, patients in shock in whom a PC method was inserted were included. CO was measure using the PC and thermodilution methods before and after a fluid challenge indicated by the physician. The correlation coefficient was measured, the diagram of Bland and Altman was built and the percentage of error (Critchley and Critchley method) was calculated. The ability of PC to diagnose fluid responsiveness was assessed using a receiver operating characteristics (ROC) curve. RESULTS: Sixty-two fluid challenges were performed in 37 included patients. After fluid challenge, r(2) was 0.05 (P<0.01), the bias between PC and thermodilution was 0.3 +/- 1.2L/min and the percentage of error was 36%. The area of the ROC curve was 0.601 [0.468-0.723]. CONCLUSION: In ICU patients with shock, PC cannot replace thermodilution to diagnose fluid responsiveness. PMID- 22050835 TI - Kappaphycus alvarezii as a source of bioethanol. AB - The present study describes production of bio-ethanol from fresh red alga, Kappaphycus alvarezii. It was crushed to expel sap--a biofertilizer--while residual biomass was saccharified at 100 degrees C in 0.9 N H2SO4. The hydrolysate was repeatedly treated with additional granules to achieve desired reducing sugar concentration. The best yields for saccharification, inclusive of sugar loss in residue, were 26.2% and 30.6% (w/w) at laboratory (250 g) and bench (16 kg) scales, respectively. The hydrolysate was neutralized with lime and the filtrate was desalted by electrodialysis. Saccharomyces cerevisiae (NCIM 3523) was used for ethanol production from this non-traditional bio-resource. Fermentation at laboratory and bench scales converted ca. 80% of reducing sugar into ethanol in near quantitative selectivity. A petrol vehicle was successfully run with E10 gasoline made from the seaweed-based ethanol. Co-production of ethanol and bio-fertilizer from this seaweed may emerge as a promising alternative to land-based bio-ethanol. PMID- 22050836 TI - Evaluation of alkaline pretreatment temperature on a multi-product basis for the co-production of glucose and hemicellulose based films from lignocellulosic biomass. AB - Cotton stalks were subjected to alkaline pretreatment for the co-production of glucose and hemicellulose based films with a multi-product approach. Three pretreatment temperatures (25, 60 and 90 degrees C) were evaluated for their effects both on the glucose yield and on the properties of hemicellulose based films. Compared to untreated cotton stalks, the glucose yields were enhanced 3.9, 4.1 and 4.2 times for pretreatments conducted at 25, 60 and 90 degrees C, respectively. The pretreatment temperature of 90 degrees C was detrimental in terms of film formation. Tensile energy to break values of the films obtained after pretreatments conducted at 25, 60 and 90 degrees C were 1.1, 0.8, and 0.4 MJ/m3, respectively. The hemicellulosic part of the process, which considers the production of hemicellulose based films, should govern the pretreatment temperature since it was more responsive to the changes in the pretreatment temperature compared to the cellulosic part that accounts for glucose production. PMID- 22050837 TI - Enhancing aerobic granulation for biological nutrient removal from domestic wastewater. AB - This study focuses on the enhancement of aerobic granulation and biological nutrient removal maintenance treating domestic wastewater. Two sequencing batch reactors (SBRs) were inoculated with either only floccular sludge (100%-floc SBR) or supplemented with 10% crushed granules (90%-floc SBR). Granules developed in both reactors. The 100%-floc SBR achieved 75% of nitrogen and 93% of phosphorus removal at the end of the performance, but some floccular sludge remained in the system. The 90%-floc SBR became fully granulated and finished with 84% and 99% of nitrogen and phosphorus removal, respectively. Regarding biological phosphorus removal, nitrite was identified as an inhibitor of the process. Nitrite levels lower than 5 mg N-NO2-L(-1) were used for anoxic phosphate uptake while higher concentrations inhibited the process. PMID- 22050838 TI - Microbial community and biomass characteristics associated severe membrane fouling during start-up of a hybrid anoxic-oxic membrane bioreactor. AB - In MBR, severe membrane fouling is often observed in the initial phase in which biomass is yet fully acclimated and stabilized in terms of microbial community structure and biomass characteristics. The focus of this study was to investigate the microbial community development and its influence on biomass characteristics and membrane fouling during start-up of a hybrid anoxic-oxic MBR. PCR-DGGE analysis indicated that the microbial community shifted in start-up period when a severe membrane fouling was observed. Small particle size, high fractal dimension (DF) and high EPS production, which were closely associated with microbial community, were found to be the major contributors to the severe fouling. Microbial community development was most likely the ultimate factor responsible for the severe membrane fouling. PMID- 22050839 TI - Characterization of Spanish biomass wastes for energy use. AB - Energy plays an important role in the world's present and future. The best way to absorb the huge increase in energy demands is through diversification. In this context biomass appears as an attractive source for a number of environmental, economical, political and social reasons. There are several techniques used to obtain energy from biomass. Among these techniques, the most commonly used throughout the world is a thermo-chemical process to obtain heat. To optimize the combustion process in adequate reactors, a comprehensive study of the characterization of biomass fuel properties is needed, which includes proximate analysis (determination of moisture, ash, volatile and fixed carbon content), ultimate analysis (C, H, N, S and O composition) and calorimetry, focusing on biomass fuels obtained in Spain. PMID- 22050840 TI - Microwave-assisted preparation and adsorption performance of activated carbon from biodiesel industry solid reside: influence of operational parameters. AB - Preparation of activated carbon has been attempted using KOH as activating agent by microwave heating from biodiesel industry solid residue, oil palm empty fruit bunch (EFBAC). The significance of chemical impregnation ratio (IR), microwave power and activation time on the properties of activated carbon were investigated. The optimum condition has been identified at the IR of 1.0, microwave power of 600 W and activation time of 7 min. EFBAC was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy and nitrogen adsorption isotherm. The surface chemistry was examined by zeta potential measurement, determination of surface acidity/basicity, while the adsorptive property was quantified using methylene blue as dye model compound. The optimum conditions resulted in activated carbon with a monolayer adsorption capacity of 395.30 mg/g and carbon yield of 73.78%, while the BET surface area and total pore volume were corresponding to 1372 m2/g and 0.76 cm3/g, respectively. PMID- 22050841 TI - Anterior and posterior segment photography. An alternative approach using a dSLR camera adaptor. AB - PURPOSE: To describe a novel digital single lens reflex (dSLR) camera adaptor for anterior and posterior segment photography. METHODS: The adaptor was used to evaluate canine, feline, and equine patients presenting to Tufts Ophthalmology service. Anterior segment imaging was conducted with the adaptor mounted between a dSLR camera body (Canon 7D) and a macro lens (Canon EF-S 60mm/f2.8). Posterior segment imaging was performed with the aid of an indirect ophthalmic lens mounted in front of the macro lens. Coaxial illumination during viewing was provided by a single white light-emitting diode (LED) within the adaptor, while illumination during exposure was provided by the pop-up flash or an accessory flash. Corneal and/or lens reflections were eliminated using a pair of linear polarizers, having their azimuths at right angles to one another. RESULTS: This dSLR camera adaptor provides quality high-resolution, reflection-free, images of both the anterior and posterior segments. It was easy to transport, assemble, and handle. The necessary adjustments, positioning, and focusing required for quality images were easily performed. CONCLUSION: The described dSLR camera adaptor provides an alternative to existing imaging systems. High-resolution image acquisition occurred at a fraction of the cost of established imaging system, particularly those devoted to the posterior segment. PMID- 22050842 TI - Genome-wide analysis of mitral valve disease in Cavalier King Charles Spaniels. AB - The Cavalier King Charles Spaniel (CKCS) is prone to severe early onset mitral valve disease. In this study, 36 purebred CKCS dogs were evaluated for mitral valve murmur and divided into early and late onset groups. A genome-wide genetic approach was used to assess whether the condition is determined by a small number of genetic factors. There were no regions of highly discrepant homo/heterozygosity in the two groups. Similarly, there was no evidence for loci associated with mitral valve murmur in a genome-wide association study. This analysis suggests that familial occurrence of mitral valve murmur in the CKCS breed is not due to a single major gene effect, indicating that breeding strategies to eliminate the disease cannot be based on genotype information at this time. PMID- 22050843 TI - Hypoxia-inducible factor 1-mediated human GATA1 induction promotes erythroid differentiation under hypoxic conditions. AB - Hypoxia-inducible factor promotes erythropoiesis through coordinated cell type specific hypoxia responses. GATA1 is essential to normal erythropoiesis and plays a crucial role in erythroid differentiation. In this study, we show that hypoxia induced GATA1 expression is mediated by HIF1 in erythroid cells. Under hypoxic conditions, significantly increased GATA1 mRNA and protein levels were detected in K562 cells and erythroid induction cultures of CD34(+) haematopoietic stem/progenitor cells. Enforced HIF1alpha expression increased GATA1 expression, while HIF1alpha knockdown by RNA interference decreased GATA1 expression. In silico analysis revealed one potential hypoxia response element (HRE). The results from reporter gene and mutation analysis suggested that this element is necessary for hypoxic response. Chromatin immunoprecipitation (ChIP)-PCR showed that the putative HRE was recognized and bound by HIF1 in vivo. These results demonstrate that the up-regulation of GATA1 during hypoxia is directly mediated by HIF1.The mRNA expression of some erythroid differentiation markers was increased under hypoxic conditions, but decreased with RNA interference of HIF1alpha or GATA1. Flow cytometry analysis also indicated that hypoxia, desferrioxamine or CoCl(2) induced expression of erythroid surface markers CD71 and CD235a, while expression repression of HIF1alpha or GATA1 by RNA interference led to a decreased expression of CD235a. These results suggested that HIF1 mediated GATA1 up-regulation promotes erythropoiesis in order to satisfy the needs of an organism under hypoxic conditions. PMID- 22050844 TI - Postoperative glaucoma in the Labrador Retriever: incidence, risk factors, and visual outcome following routine phacoemulsification. AB - OBJECTIVE: To evaluate the incidence and risk factors associated with development of postoperative glaucoma in the Labrador Retriever following routine phacoemulsification. METHODS: Medical records from Labradors and a randomly selected population of non-Labradors were retrospectively evaluated. Signalment, diabetic status, cataract stage, gonioscopic findings, presence of preoperative lens-induced uveitis, development of postoperative hypertension (POH), postoperative glaucoma and postoperative visual status were recorded for each patient. Survival curves were developed using the Cox proportional hazards model. RESULTS: Forty-two Labradors (66 eyes) and 199 non-Labradors (314 eyes) were included. The incidence of POH was significantly higher in Labradors (33%) than non-Labradors (18%). Labradors were at significantly increased risk of postoperative glaucoma and blindness compared to non-Labradors. Estimated probabilities of postoperative glaucoma in Labradors were 23%, 25%, 30% and 35% at weeks 4, 26, 52 and 104, respectively, compared with 5%, 6%, 7% and 9% at weeks 4, 26, 52 and 104, respectively, in non-Labradors. Estimated probabilities of postoperative blindness in Labradors were 5%, 9%, 15% and 27% at weeks 4, 26, 52 and 104, respectively, compared with 2%, 3%, 5% and 10% at weeks 4, 26, 52 and 104, respectively, in non-Labradors. Risk factors for the development of glaucoma in Labradors included increasing age and development of POH. No statistically significant risk factors for the development of glaucoma were identified in non Labradors. CONCLUSIONS: Labradors are at increased risk of glaucoma and blindness following phacoemulsification compared with non-Labradors. POH and increasing age represent risk factors for the development of postoperative glaucoma in Labradors. PMID- 22050845 TI - Role of Trpc channels, Stim1 and Orai1 in PGF(2alpha)-induced calcium signaling in NRK fibroblasts. AB - Normal rat kidney (NRK) fibroblasts exhibit growth-dependent changes in electrophysiological properties and intracellular calcium dynamics. The transition from a quiescent state to a density-arrested state results in altered calcium entry characteristics. This coincides with modulation of the expression of the genes encoding the calcium channels Trpc1, Trpc6 and Orai1, and of the intracellular calcium sensor Stim1. In the present study we have used gene selective short hairpin (sh) RNAs against these various genes to investigate their role in (a) capacitative store-operated calcium entry (SOCE); (b) non capacitative OAG-induced receptor-operated calcium entry (ROCE); and (c) prostaglandin F(2alpha) (PGF(2alpha))-induced Ca(2+)-oscillations in NRK fibroblasts. Intracellular calcium measurements revealed that knockdown of the genes encoding Trpc1, Orai1 and Stim1 each caused a significant reduction of SOCE in NRK cells, whereas knockdown of the gene encoding Trpc6 reduced only the OAG induced ROCE. Furthermore, our data show that knockdown of the genes encoding Trpc1, Orai1 and Stim1, but not Trpc6, substantially reduced the frequency (up to 60%) of PGF(2alpha)-induced Ca(2+) oscillations in NRK cells. These results indicate that in NRK cells distinct calcium channels control the processes of SOCE, ROCE and PGF(2alpha)-induced Ca(2+) oscillations. PMID- 22050846 TI - General overview: biomarkers in neuroscience research. AB - Biomarkers are in demand for disease diagnosis, treatment response monitoring, and development of novel therapeutics. Biomarker discovery in neuroscience is challenging due to absence of robust molecular correlates and the interpatient heterogeneity that characterizes neuropsychiatric disorders. Because of the complexity of these disorders, a panel of biomarkers derived from different platforms will be required to precisely reflect disease-related alterations. Animal models of psychiatric phenotypes as well as -omics and imaging methodologies are important tools for biomarker discovery. However, the limitations of current research concerning sample handling and collection, candidate biomarker validation, and a lack of interdisciplinary approaches need to be addressed. Ultimately, the coordinated effort of relevant stakeholders including researchers, physicians, and funding organizations together with standardization initiatives will be vital to overcome the present challenges and to advance personalized health care using sensitive and specific biomarkers. PMID- 22050847 TI - Imaging brain microglial activation using positron emission tomography and translocator protein-specific radioligands. AB - Microglia are rapidly activated by a wide range of neuropathological insults. Quantifying microglial density in vivo would allow a new, potentially important range of clinic-pathological correlations. Microglia express the 18kDa translocator protein (TSPO) which can be quantified by the positron emission tomography (PET) ligand [(11)C]PK11195, although signal quantification is limited by nonspecific binding. New generation TSPO radioligands with an improved signal to-noise ratio are now available, but variation in their binding affinity for the TSPO between subjects complicates their use. This review describes the principles of PET imaging, the rationale and challenges in targeting the TSPO as means of quantifying microglial activation in vivo, and disease applications that have been studied with TSPO-PET hitherto. PMID- 22050848 TI - The utility of gene expression in blood cells for diagnosing neuropsychiatric disorders. AB - Objective diagnostic tools are required for neuropsychiatric disorders. Gene expression in blood cells may provide such a tool and has already been used to construct classifiers capable of diagnosing many human diseases. This chapter discusses the use of microarray gene expression data to construct diagnostic classifiers for neuropsychiatric disorders. The potential pitfalls of microarray gene expression analysis and the experimental design and methods suitable for classifier construction are described in detail. A review of studies that have analyzed gene expression in blood cells from patients with neuropsychiatric disorders is presented with an emphasis on the feasibility of generating a diagnostic classifier for schizophrenia. Finally, the future directions of the field are discussed with respect to using blood gene expression to tailor antipsychotic medications to individual patients, applying microRNA expression for diagnostic purposes, as well as the implications of next-generation sequencing technologies for gene expression analysis. PMID- 22050849 TI - Proteomic technologies for biomarker studies in psychiatry: advances and needs. AB - In the postgenome era, proteomics has arisen as a promising tool for more complete comprehension of diseases and for biomarker discovery. Some of these objectives have already been partly achieved for illnesses such as cancer. In the case of psychiatric conditions, however, proteomic advances have had a less profound impact. Here, we outline the necessity of improving and applying proteomic methods for biomarker discovery and validation in the field of psychiatric disorders. While proteomic-based applications in neurosciences have increased in accuracy and sensitivity over the past 10 years, the development of orthogonal validation technologies has fallen behind. These issues are discussed along with the importance of integrating systems biology approaches and combining proteomics with other research approaches. The future development of such technologies may put proteomics closer to clinical applications in psychiatry. PMID- 22050850 TI - Converging evidence of blood-based biomarkers for schizophrenia: an update. AB - This chapter has carried out a review of the literature and combined this with the results of in-house studies to identify candidate blood-based biomarkers for schizophrenia and antipsychotic drug response. Literature searches retrieved 185 publications describing a total of 273 schizophrenia biomarkers identified in serum and/or plasma. Examination of seven in-house multicenter studies resulted in the identification of 137 serum/plasma biomarkers. Taken together, the findings suggested an ongoing immunological and inflammatory process in schizophrenia. This was accompanied by altered cortisol levels which suggested activated stress response and altered hypothalamic-pituitary-adrenal axis function in these patients. The authors conclude that such biomarkers may prove useful as additional parameters for characterizing specific immune and/or metabolic or hormonal subsystems in schizophrenia and might, therefore, facilitate the development of future patient stratification and personalized medicine strategies. PMID- 22050851 TI - Abnormalities in metabolism and hypothalamic-pituitary-adrenal axis function in schizophrenia. AB - For decades, evidence has been emerging that the pathogenesis of schizophrenia can involve perturbations in metabolic and hypothalamic-pituitary-adrenal (HPA) axis pathways. Variations in manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response, including the finding that a high proportion of subjects fail to respond to current antipsychotic medications. Here, we review the evidence for abnormalities in metabolism and HPA axis regulation in schizophrenia. Such studies may prove critical for increasing our understanding of the multidimensional nature of psychiatric illnesses and for improving the timeliness and accuracy of diagnosis. Stratification of subjects according to molecular phenotype reflecting the disease state or trait could help to improve existing treatments through application of novel personalized medicine strategies and by the development of much-needed novel antipsychotic agents. PMID- 22050852 TI - Immune and neuroimmune alterations in mood disorders and schizophrenia. AB - A large number of publications over the past 20 years have indicated that immune system function is altered in schizophrenia and mood disorder patients. This chapter reviews the evidence, which suggests that a proinflammatory state of the cytokine network induces psychopathologic symptoms and may be involved in the pathogenesis and pathophysiology of these major mental illnesses. The authors also present recent data, which relates immune activation to present theories on the influence of activated immune cells in altering brain function. They also focus on the role of the environment in immune activation and on the role of the microbiome and gut flora. Increased understanding of such factors could help in the development of novel treatment strategies and improved clinical management of mental disorders. PMID- 22050853 TI - Behavioral and molecular biomarkers in translational animal models for neuropsychiatric disorders. AB - Modeling neuropsychiatric disorders in animals poses a significant challenge due to the subjective nature of diverse often overlapping symptoms, lack of objective biomarkers and diagnostics, and the rudimentary understanding of the pathophysiology. Successful translational research requires animal models that can inform about disease mechanisms and therapeutic targets. Here, we review behavioral and neurobiological findings from selected animal models, based on presumed etiology and risk factors, for schizophrenia, bipolar disorder, and major depressive disorder. We focus on the use of appropriate statistical tools and newly developed Research Domain Criteria (RDoC) to link biomarkers from animal models with the human disease. We argue that this approach will lead to development of only the most robust animal models for specific psychiatric disorders and may ultimately lead to better understanding of the pathophysiology and identification of novel biomarkers and therapeutic targets. PMID- 22050854 TI - Stem cell models for biomarker discovery in brain disease. AB - Most brain diseases arise from interactions between complex genetic and environmental risk factors. Finding biomarkers for brain diseases will require appropriate cellular models to identify dysregulated cell functions and disease associated biochemistries. Patient-derived stem cells hold great potential as models of brain diseases. Stem cells can proliferate and can be banked, stored, and thawed for genomic, proteomic, and functional studies. Patient-derived, induced pluripotent stem cells and adult stem cells from the olfactory organ in the nose are already giving novel insights into a number of brain diseases, including Parkinson's disease and schizophrenia. Biomarker discovery may be possible from investigating disease-associated cell biologies in patient-derived stem cells. PMID- 22050855 TI - The application of multiplexed assay systems for molecular diagnostics. AB - For decades, the diagnosis of schizophrenia and other psychiatric disorders has relied on subjective assessments such as Diagnostic and Statistical Manual criteria. There is now increasing interest in the identification of altered molecular patterns in blood and other accessible body fluids that can be used to help identify, stratify, and monitor psychiatric patients. Since shorter periods of psychosis are associated with a better prognosis, an accurate molecular test may lead to early intervention and thereby improve patient outcomes. In addition, such a test would open up the possibility to stratify more accurately the disease and could represent a novel translational medicine tool, which is crucial for the discovery and development of more efficacious therapies. PMID- 22050856 TI - Algorithm development for diagnostic biomarker assays. AB - This chapter describes the ground-breaking development of a serum-based test to help confirm the diagnosis of schizophrenia. A multiplex panel of 51 immunoassays was developed that allowed reproducible identification of schizophrenia patients compared to controls with high sensitivity and specificity. Validation of this test consisted of developing a linear support vector machine decision rule and testing its performance using cross-validation. This resulted in readjustment of the panel and algorithm to a smaller set of 40 robust assays, along with a simple procedure for maintenance and recalibration across future measurement changes associated with different reagent lots. The resulting decision rule delivered a sensitive and specific prediction for presence of schizophrenia in subjects compared to matched controls, with a receiver operating characteristic area under the curve of 88%. Performance of the recalibrated decision rule remained constant across lot changes, ensuring consistency and accuracy. PMID- 22050857 TI - Challenges of introducing new biomarker products for neuropsychiatric disorders into the market. AB - There are many challenges associated with the discovery and development of serum based biomarkers for psychiatric disorders such as schizophrenia. Here, we review these challenges from the point of view of psychiatrists, general practitioners, the regulatory agencies, and biomarker scientists. There is a general opinion in psychiatric medicine that improvements over the current subjective tests are essential. Despite this, there is a reluctance to accept that peripheral molecules can do the job any better. In addition, psychiatrists find it difficult to accept that peripheral molecules, such as those found in blood, can reflect what is happening in the brain. However, the regulatory health authorities now consider biomarkers as important for the future of drug development and have called for efforts to modernize methods, tools, and techniques for the purpose of developing more efficient and safer drugs. We also describe here the development of the first ever molecular blood test for schizophrenia, and its reception in the market place, as a case in point. PMID- 22050858 TI - Toward personalized medicine in the neuropsychiatric field. AB - There are great expectations for the personalized medicine approach to address the therapeutic needs of patients in the twenty-first century. Advances in human genome science and molecular innovations in neuroscience have encouraged the pharmaceutical industry to focus beyond broad spectrum population therapeutics- the driving force behind the "blockbuster" product concept--to personalized medicine. For central nervous system (CNS) therapeutics, repeated failures in converting scientific discoveries to clinical trial successes and regulatory approvals have precipitated a drug pipeline crisis and eroded confidence in the industry. This chapter describes how innovations in genomics and translational medicine can impact the future of neuropsychiatry and deconvolute the complexity of psychiatric diseases from symptoms biology. A targeted and consistent investment is needed to restore confidence in translating science into clinical success. PMID- 22050859 TI - Clinical utility of serum biomarkers for major psychiatric disorders. AB - There is a major unmet clinical need for molecular blood-based biomarkers in studies of major psychiatric disorders. Thus far, identification of such biomarkers has been sparse, most likely due to the fact that this is reliant on long-standing diagnostic concepts used in psychiatry, which are notoriously heterogeneous. Also, identification of biomarkers for a syndrome that has already been categorized based on clinical phenomenology is not useful in the clinic. This chapter describes the need for innovative approaches for identification of biomarkers which can been used to classify at-risk patients such as youngsters with prodromal symptoms for psychosis and existing patients who are likely to progress to more severe states. The authors argued for the use of broader categories of related patients and to deconstruct the traditional diagnoses in favor of molecular biomarker profiles. PMID- 22050860 TI - The future: biomarkers, biosensors, neuroinformatics, and e-neuropsychiatry. AB - The emergence of molecular biomarkers for psychological, psychiatric, and neurodegenerative disorders is beginning to change current diagnostic paradigms for this debilitating family of mental illnesses. The development of new genomic, proteomic, and metabolomic tools has created the prospect of sensitive and specific biochemical tests to replace traditional pen-and-paper questionnaires. In the future, the realization of biosensor technologies, point-of-care testing, and the fusion of clinical biomarker data, electroencephalogram, and MRI data with the patient's past medical history, biopatterns, and prognosis may create personalized bioprofiles or fingerprints for brain disorders. Further, the application of mobile communications technology and grid computing to support data-, computation- and knowledge-based tasks will assist disease prediction, diagnosis, prognosis, and compliance monitoring. It is anticipated that, ultimately, mobile devices could become the next generation of personalized pharmacies. PMID- 22050861 TI - Biomarkers of neurological and psychiatric disease. Preface. PMID- 22050862 TI - The impact of clinical data on the evaluation of tibial fracture healing. AB - BACKGROUND: Radiographic healing is a common outcome measure in orthopedic trials and adjudication by outcome assessors is often conducted on the basis of plain films alone. The degree to which this process reflects clinical practice, in which both plain films and clinical notes are available, is uncertain. We explored the effect of adding clinical notes to radiographs in the adjudication process of a feasibility trial of tibial shaft fractures. METHODS: Radiographic and clinical data from a multicenter randomized controlled trial of 51 patients with operatively treated tibial fractures formed the basis of the study data. At the completion of the trial, serial radiographs (anteroposterior and lateral) were independently evaluated for progression of fracture healing, defined as bridging of at least 3 of 4 cortices, by an adjudication committee comprised of 3 blinded orthopaedic trauma surgeons. Immediately after determination of radiographic time to healing, each surgeon was provided with clinical notes associated with each radiographic follow up visit and asked to re-visit their initial impression. Consensus was achieved for both adjudications. We calculated the percentage of time to healing consensus decisions that changed after evaluation of clinical notes. We further examined the contents of clinical notes and their relative influence on the committee's decisions. RESULTS: 47 of 51 patients were determined to have healed radiographically during the trial follow up period, and consideration of clinical notes resulted in a change of 40% (19 of 47) of time to healing consensus decisions; however, revised decisions were equally likely to support an earlier or a later time to healing. Clinical notes that resulted in a change to either a 'healed' or a 'not healed' decision contained significantly more comments of either pain resolution or deterioration, respectively, resumption of or failure to resume weightbearing, or either return or no return to work/pre-injury activities (p < 0.001). CONCLUSIONS: The addition of clinical notes to the adjudication of radiographic fracture healing changed the outcome decision in a substantial number of cases. Orthopedic trialists should consider the addition of clinical notes to adjudication material in studies of fracture healing in order to enhance the generalizability of their results. TRIAL REGISTRATION: The TRUST trial was registered [ID NCT00667849] at http://clinicaltrials.gov/ct2/show/NCT00667849. PMID- 22050865 TI - Applied Radiation and Isotopes. Preface. PMID- 22050864 TI - Blastocyst-stage versus cleavage-stage embryo transfer in women with high oestradiol concentrations: randomized controlled trial. AB - This prospective, randomized, controlled trial tested the hypothesis that delaying embryo transfer to the blastocyst stage can increase the probability of clinical pregnancy and live birth in women with high oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) undergoing intracytoplasmic sperm injection using the long protocol. A total of 200 women with oestradiol >3000 pg/ml on the HCG day with four or more good-quality, day-3 embryos were randomized in a 1:1 ratio to undergo day-3 or day-5 embryo transfer. Clinical pregnancy rates (CPR; 41% versus 59%; relative risk 0.70, 95% CI 0.52-0.93) and ongoing pregnancy/live-birth rates (35% versus 52%; relative risk 0.67, 95% CI 0.46-0.93) were lower in women undergoing cleavage-stage than blastocyst-stage embryo transfer. Using receiver operating characteristic curves, among women undergoing cleavage-stage embryo transfer, a detrimental cut-off value for not achieving pregnancy for oestradiol was 4200 pg/ml, with lower CPR and ongoing pregnancy/live-birth rates (P = 0.006 and 0.02, respectively). No detrimental cut off value for oestradiol was identified among women undergoing blastocyst-stage embryo transfer. Delaying embryo transfer to the blastocyst stage can increase the probability of pregnancy in women with high oestradiol on the HCG day PMID- 22050863 TI - Early identification of and proactive palliative care for patients in general practice, incentive and methods of a randomized controlled trial. AB - BACKGROUND: According to the Word Health Organization, patients who can benefit from palliative care should be identified earlier to enable proactive palliative care. Up to now, this is not common practice and has hardly been addressed in scientific literature. Still, palliative care is limited to the terminal phase and restricted to patients with cancer. Therefore, we trained general practitioners (GPs) in identifying palliative patients in an earlier phase of their disease trajectory and in delivering structured proactive palliative care. The aim of our study is to determine if this training, in combination with consulting an expert in palliative care regarding each palliative patient's tailored care plan, can improve different aspects of the quality of the remaining life of patients with severe chronic diseases such as chronic obstructive pulmonary disease, congestive heart failure and cancer. METHODS/DESIGN: A two armed randomized controlled trial was performed. As outcome variables we studied: place of death, number of hospital admissions and number of GP out of hours contacts. DISCUSSION: We expect that this study will increase the number of identified palliative care patients and improve different aspects of quality of palliative care. This is of importance to improve palliative care for patients with COPD, CHF and cancer and their informal caregivers, and to empower the GP. The study protocol is described and possible strengths and weaknesses and possible consequences have been outlined. TRIAL REGISTRATION: The Netherlands National Trial Register: NTR2815. PMID- 22050866 TI - Conjunctivitis and ulcerative keratitis secondary to conjunctival plant foreign bodies in a herd of alpacas (Lama Pacos). AB - PURPOSE: To describe six cases of conjunctivitis and ulcerative keratitis secondary to plant foreign bodies from weed-contaminated grass hay which were lodged within the temporal conjunctival fornix in a herd of alpacas. METHODS: A total of 21 alpacas from the same farm developed blepharospasm and mucopurulent ocular discharge. Six of the 21 were evaluated at the University of Tennessee College of Veterinary Medicine within a 2-week period. The six animals evaluated received an ophthalmic examination including slit-lamp biomicroscopy, fluorescein staining, and topical corneal anesthesia for foreign body removal when necessary. RESULTS: Six animals had conjunctivitis characterized by hyperemia and mucopurulent discharge. Five animals had superficial ulcerative keratitis with intense corneal neovascularization and edema. In all cases, the keratitis was located at the temporal limbus. Seven plant foreign bodies were observed and were removed following topical corneal anesthesia in five animals. The plant seeds were identified as three common weed species found in orchard grass hay. Complete resolution of all clinical signs was achieved with foreign body removal and medical therapy. CONCLUSIONS: Fan-shaped temporal corneal ulcers may signify the presence of conjunctival foreign bodies in alpacas. Plant foreign bodies should be considered in addition to ocular infection when multiple animals of a herd are affected as outbreaks may occur with weed-contaminated hay. PMID- 22050867 TI - Vivax malaria in Mauritania includes infection of a Duffy-negative individual. AB - BACKGROUND: Duffy blood group polymorphisms are important in areas where Plasmodium vivax is present because this surface antigen is thought to act as a key receptor for this parasite. In the present study, Duffy blood group genotyping was performed in febrile uninfected and P. vivax-infected patients living in the city of Nouakchott, Mauritania. METHODS: Plasmodium vivax was identified by real-time PCR. The Duffy blood group genotypes were determined by standard PCR followed by sequencing of the promoter region and exon 2 of the Duffy gene in 277 febrile individuals. Fisher's exact test was performed in order to assess the significance of variables. RESULTS: In the Moorish population, a high frequency of the FYBES/FYBES genotype was observed in uninfected individuals (27.8%), whereas no P. vivax-infected patient had this genotype. This was followed by a high level of FYA/FYB, FYB/FYB, FYB/FYBES and FYA/FYBES genotype frequencies, both in the P. vivax-infected and uninfected patients. In other ethnic groups (Poular, Soninke, Wolof), only the FYBES/FYBES genotype was found in uninfected patients, whereas the FYA/FYBES genotype was observed in two P. vivax-infected patients. In addition, one patient belonging to the Wolof ethnic group presented the FYBES/FYBES genotype and was infected by P. vivax. CONCLUSIONS: This study presents the Duffy blood group polymorphisms in Nouakchott City and demonstrates that in Mauritania, P. vivax is able to infect Duffy-negative patients. Further studies are necessary to identify the process that enables this Duffy-independent P. vivax invasion of human red blood cells. PMID- 22050868 TI - Extended spectrum of human glucose-6-phosphatase catalytic subunit 3 deficiency: novel genotypes and phenotypic variability in severe congenital neutropenia. AB - OBJECTIVE: To delineate the phenotypic and molecular spectrum of patients with a syndromic variant of severe congenital neutropenia (SCN) due to mutations in the gene encoding glucose-6-phosphatase catalytic subunit 3 (G6PC3). STUDY DESIGN: Patients with syndromic SCN were characterized for associated malformations and referred to us for G6PC3 mutational analysis. RESULTS: In a cohort of 31 patients with syndromic SCN, we identified 16 patients with G6PC3 deficiency including 11 patients with novel biallelic mutations. We show that nonhematologic features of G6PC3 deficiency are good predictive indicators for mutations in G6PC3. Additionally, we demonstrate genetic variability in this disease and define novel features such as growth hormone deficiency, genital malformations, disrupted bone remodeling, and abnormalities of the integument. G6PC3 mutations may be associated with hydronephrosis or facial dysmorphism. The risk of transition to myelodysplastic syndrome/acute myeloid leukemia may be lower than in other genetically defined SCN subgroups. CONCLUSIONS: The phenotypic and molecular spectrum in G6PC3 deficiency is wider than previously appreciated. The risk of transition to myelodysplastic syndrome or acute myeloid leukemia may be lower in G6PC3 deficiency compared with other subgroups of SCN. PMID- 22050869 TI - Comparative effectiveness of different types of splenectomy for children with congenital hemolytic anemias. AB - OBJECTIVE: To compare the effectiveness of different types of splenectomy in children with congenital hemolytic anemias. STUDY DESIGN: We constructed key questions that addressed outcomes relevant to clinicians and families on effects of partial or total splenectomy, including hematologic effect, splenic function, and the risk of adverse events. We identified from Pubmed and Embase 703 studies that evaluated different types of splenectomy and accepted 93 studies that satisfied entry criteria. We graded the quality of each report and summarized the overall strength of research evidence for each key question. RESULTS: We did not identify any randomized clinical trials. All types of splenectomy have favorable clinical outcomes in most diseases. We did not identify any hematologic advantage of laparoscopy compared with laparotomy. Adverse events are uncommon in most studies and are minimized with use of laparoscopy. CONCLUSIONS: There is a need for randomized clinical trials and improved data collection of different types of splenectomy in congenital hemolytic anemias. Outcomes studied should address the concerns of families and clinicians to assess the risks and benefits of various treatments. PMID- 22050870 TI - Pharmacokinetics of intravenous lorazepam in pediatric patients with and without status epilepticus. AB - OBJECTIVE: To evaluate the single dose pharmacokinetics of an intravenous dose of lorazepam in pediatric patients treated for status epilepticus (SE) or with a history of SE. STUDY DESIGN: Ten hospitals in the Pediatric Emergency Care Applied Research Network enlisted patients 3 months to 17 years with convulsive SE (status cohort) or for a traditional pharmacokinetics study (elective cohort). Sparse sampling was used for the status cohort, and intensive sampling was used for the elective cohort. Non-compartmental analyses were performed on the elective cohort, and served to nest compartmental population pharmacokinetics analysis for both cohorts. RESULTS: A total of 48 patients in the status cohort and 15 patients in the elective cohort were enrolled. Median age was 7 years, 2 months. The population pharmacokinetics parameters were: clearance, 1.2 mL/min/kg; half-life, 16.8 hours; and volume of distribution, 1.5 L/kg. On the basis of the pharmacokinetics model, a 0.1 mg/kg dose is expected to achieve concentrations of approximately 100 ng/mL and maintain concentrations >30 to 50 ng/mL for 6 to 12 hours. A second dose of 0.05 mg/kg would achieve desired therapeutic serum levels for approximately 12 hours without excessive sedation. Age-dependent dosing is not necessary beyond using a maximum initial dose of 4 mg. CONCLUSIONS: Lorazepam pharmacokinetics in convulsive SE is similar to earlier pharmacokinetics measured in pediatric patients with cancer, except for longer half-life, and similar to adult pharmacokinetics parameters except for increased clearance. PMID- 22050872 TI - Should cardiac involvement be included in the criteria for diagnosis of Churg Strauss syndrome? PMID- 22050873 TI - Hyperventilation during exercise in very low birth weight school-age children may implicate inspiratory muscle weakness. AB - OBJECTIVES: To study the ventilatory response during exercise in 8- to 10-year old children born in 1998 to 2000 with a birthweight <1500 g (very low birthweight [VLBW]). STUDY DESIGN: We studied 19 VLBW children and 20 full-term children paired for age and sex. A physical activity questionnaire was administered. Lean body mass, spirometry, and maximal inspiratory pressure were assessed at rest. Gas exchange, breathing pattern, and the tension-time index of the inspiratory muscles, a noninvasive indicator of inspiratory muscle effort, were evaluated during a continuous incremental cycling protocol. RESULTS: VLBW children had lower weight, height, lean body mass, and maximal inspiratory pressure than control subjects. Their physical activity level was not different. During exercise, they had a higher respiratory rate and minute ventilation for the same metabolic level (VCO(2)/kg) and a higher tension-time index of the inspiratory muscles for the same exercise level (percentage of maximal oxygen consumption). CONCLUSIONS: The lower inspiratory muscle strength observed in school-age VLBW children resulted in a higher inspiratory effort during incremental exercise. The rapid but not shallow breathing pattern adopted by this population during exercise may have been in response to their lower inspiratory muscle resistance to fatigue. VLBW children complaining of dyspnea should be investigated with exercise testing. PMID- 22050874 TI - Use of targeted neonatal echocardiography to prevent postoperative cardiorespiratory instability after patent ductus arteriosus ligation. AB - OBJECTIVES: To investigate the value of targeted neonatal echocardiography (TnECHO) in predicting cardiorespiratory instability after patent ductus arteriosus (PDA) ligation, and to evaluate the impact of TnECHO-directed care. STUDY DESIGN: We reviewed serial echocardiography evaluations of 62 preterm infants after PDA ligation to investigate the relationship between indices of myocardial performance and postoperative cardiorespiratory instability. A predictive model was developed based on TnECHO criteria, with targeted initiation of intravenous milrinone. A comparative evaluation was performed between matched infants in the previous era (epoch 1; n=25) and current era (epoch 2; n=27) of TnECHO-guided treatment. RESULTS: Left ventricular output <200 mL/kg/min at 1 hour after PDA ligation was a sensitive predictor of systemic hypotension and the need for inotropes, and was used for initiation of i.v. milrinone infusion in epoch 2. Infants treated with milrinone had a lower incidence of ventilation failure (15% vs 48%; P=.02) and less need for inotropes (19% vs 56%; P=.01), and showed a trend toward improved oxygenation (P=.08). CONCLUSION: TnECHO facilitates early detection of infants at greatest risk for subsequent cardiorespiratory deterioration. Administration of milrinone to neonates with low cardiac output may lead to improved postoperative stability. PMID- 22050871 TI - Evolution of encephalopathy during whole body hypothermia for neonatal hypoxic ischemic encephalopathy. AB - OBJECTIVE: To examine the predictive ability of stage of hypoxic-ischemic encephalopathy (HIE) for death or moderate/severe disability at 18 months among neonates undergoing hypothermia. STUDY DESIGN: Stage of encephalopathy was evaluated at <6 hours of age, during study intervention, and at discharge among 204 participants in the National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for HIE. HIE was examined as a predictor of outcome by regression models. RESULTS: Moderate and severe HIE occurred at <6 hours of age among 68% and 32% of 101 hypothermia group infants and 60% and 40% of 103 control group infants, respectively. At 24 and 48 hours of study intervention, infants in the hypothermia group had less severe HIE than infants in the control group. Persistence of severe HIE at 72 hours increased the risk of death or disability after controlling for treatment group. The discharge exam improved the predictive value of stage of HIE at <6 hours for death/disability. CONCLUSIONS: On serial neurologic examinations, improvement in stage of HIE was associated with cooling. Persistence of severe HIE at 72 hours and an abnormal neurologic exam at discharge were associated with a greater risk of death or disability. PMID- 22050875 TI - Upper airway complications of junctional epidermolysis bullosa. AB - OBJECTIVE: To assess the incidence of upper airway pathology in patients with junctional epidermolysis bullosa (JEB). STUDY DESIGN: We conducted a retrospective chart review of all patients with JEB who came to an interdisciplinary epidermolysis bullosa center at a tertiary care institution between 2004 and 2010. RESULTS: Twenty-five patients with JEB were identified, and 12 patients were seen in the otolaryngology clinic (age range, 2 months-15 years; 8 male, 4 female). Of the 12 patients, 8 underwent rigid laryngoscopy and bronchoscopy for upper respiratory tract symptoms; 7 of these patients displayed laryngeal pathology, and 5 of them underwent surgical intervention with successful resolution of symptoms. Furthermore, none of these patients had any short- or long-term complications from their surgery. A strict protocol and a precise problem-focused cold surgical technique were used in these cases to protect skin and mucus membranes. CONCLUSION: With appropriate precautions, endoscopic laryngeal surgery can be safe and effective in patients with JEB and larygnotracheal disease. Endoscopic laryngeal surgery is feasible when indicated for these patients. PMID- 22050876 TI - The pathogenesis and management of the coagulopathy of acute promyelocytic leukaemia. AB - Coagulopathy occurs in most patients with (APML) and is life-threatening; therefore prompt diagnosis and recognition of any coagulation defect is imperative. Unfortunately haemorrhage remains a major cause of early death, preventing some from reaching treatment. The coagulopathy is caused directly or indirectly by the leukaemic cells through expression of activators of coagulation and fibrinolysis, proteases and cytokine generation, compounded by failure of platelet production due to marrow invasion. At presentation the predominant feature is usually hyperfibrinolysis. Since the introduction of all-trans retinoic acid (ATRA), patient outcome has dramatically improved; yet, haemorrhagic complications remain the most frequent cause of mortality. Thrombotic complications occur but are less well recognized and potentially underreported. Supportive measures and prompt initiation of ATRA currently represent the mainstay of treatment of the coagulopathy in patients with suspected APML, but unanswered questions remain as to the optimal approach to further decrease the associated haemorrhagic and thrombotic risks. In particular, it is unclear how to best predict and monitor the coagulopathy; whether there is a role for the early use of antifibrinolytics; the most appropriate trigger for giving fibrinogen replacement and the value of low-dose anticoagulation to suppress coagulation activation once fibrinolysis has been suppressed. PMID- 22050877 TI - Limits of infrainguinal bypass surgery for critical leg ischemia in high-risk patients (Finnvasc score 3-4). AB - BACKGROUND: The aim of the present study was to compare the early- and midterm outcomes after infrainguinal bypass surgery in the treatment of low- and high risk patients with critical limb ischemia (CLI) (Finnvasc score 0-2 and 3-4, respectively), and to evaluate limits of infrainguinal bypass surgery in treatment of the latter group. METHODS: Two hundred seventy-four infrainguinal bypass procedures performed in 218 patients were retrospectively reviewed. The Finnvasc score (range: 0-4) was calculated by assigning one point to each of four preoperative risk factors, that is, coronary artery disease, diabetes, urgency of the procedure, and gangrene. Major outcome end points were survival, limb salvage, and amputation-free survival. RESULTS: Among 274 infrainguinal bypass procedures performed for CLI, 92 procedures (33.6%) were performed in patients with Finnvasc score 3-4. They had significantly lower leg salvage (at 3-year follow-up, 53.7 vs. 70.6%; log-rank: p = 0.004), survival (at 3-year follow-up, 49.7 vs. 69.7%; log-rank: p < 0.0001), and amputation-free survival (at 3-year follow-up, 27.7 vs. 53.1%; log-rank: p < 0.0001) compared with patients with Finnvasc score 0-2. Patients with Finnvasc score 3-4 and a preoperative serum creatinine level of >150 MUmol/L had 1-year amputation-free survival of 12.5%, whereas patients with lower level of creatinine had 1-year amputation-free survival of 53.1% (p = 0.028). CONCLUSIONS: Infrainguinal bypass revascularization in CLI patients who present with Finnvasc score 3-4 can be considered at higher risk of poor intermediate outcome in terms of survival, leg salvage, and amputation-free survival. Poor outcome is particularly expected in patients with Finnvasc score 3-4 and renal failure. In this subgroup of patients, primary amputation should be considered. PMID- 22050878 TI - Femorofemoral bypass as an alternative to a direct aortic approach in daily practice: appraisal of its current indications and midterm results. AB - BACKGROUND: To assess our current practice concerning the indications and the immediate and midterm results of femorofemoral bypass. METHODS: We retrospectively included all patients, from 1997 to 2008, operated on for aortoiliac occlusive disease using an extra-anatomical bypass from a donor iliac artery or a femoral artery to the contralateral femoral artery (common or profunda artery). Demographic data, initial clinical status, characteristics of the interventions, and short- and midterm results were collected. Elective surgery was distinguished from urgent surgery (critical limb ischemia, acute ischemia, vascular infection). RESULTS: One hundred twenty-four femorofemoral bypasses were performed (103 male), mean age 68 (+/-12) years. Indications were critical limb ischemia (47.1%), intermittent claudication (38.8%), acute ischemia (12.1%), and vascular infections (1.7%). Perioperative outcomes were 5.6% mortality (elective surgery 0.0%, urgent surgery 9.7%, P = 0.02) and 27.4% morbidity without any secondary graft infections (elective surgery 22.5%, urgent surgery 31.9%, P = 0.17). Mean follow-up period was 3 years, and overall survival was 69.4% (elective surgery 88.7%, urgent surgery 56.7%, P = 0.08). At 3 years, primary patency was 81.8% and secondary patency was 89.3% (elective surgery 96.4%, urgent surgery 84.2%, P = 0.68). No significant risk factors for immediate and secondary thromboses were found. CONCLUSION: In our current practice, femorofemoral bypasses are applied mainly for urgent procedures when avoiding a direct aortic approach is mandatory, with good midterm results. Although indications are limited for good-fit patients, femorofemoral bypass has confirmed safety (no perioperative deaths, no infections) and high durability (good secondary patency). PMID- 22050879 TI - Early protection and compression of residual limbs may improve and accelerate prosthetic fit: a preliminary study. AB - BACKGROUND: The goal of rehabilitation following lower extremity amputation is to restore the highest level of independent function. As much as possible, this includes the functional use of a prosthetic device fitted to the residual limb. Early prosthetic fit depends, in turn, on rapid healing of the amputation site. METHODS: We hypothesized that compliance with a novel custom-designed amputation protection and compression system (CAPCS) to the residual limb can accelerate and improve the likelihood of successful prosthesis use. We conducted a retrospective study of all patients who were offered CAPCS by certified prosthetists (Hanger Prosthetics and Orthotics, Bethesda, MD) during the period between April 2004 and November 2009. Variables included age, sex, indication for amputation, and compliance with CAPCS. Compliance was defined as consistent observed wearing of the CAPCS as directed. The primary end point was the fitting of a prosthetic device to the amputated limb, with time to prosthetic fit being the secondary outcome. RESULTS: Out of 100 patients who were offered CAPCS (n = 100) during the study period, 76% were considered compliant (n = 76). Sixty five patients (65%) were ultimately fitted with prosthetic limbs. In multivariate analysis, we found that patients who had compliant use of CAPCS were significantly more likely to be successfully fit with prosthesis (72 vs. 42%, p = 0.005). At 100 days post amputation, the cumulative incidence of prosthesis fitting was significantly higher in CAPCS compliant patients (69.7 vs. 22.2%, p = 0.012). CONCLUSIONS: Compliant use of a CAPCS following amputation is associated with earlier and more frequent use of a prosthetic. Based on this limited data set, a conclusion can be drawn that the potential exists to significantly improve functional outcomes after amputation, but well-designed prospective studies are needed to confirm this association. PMID- 22050880 TI - Magnetic resonance imaging reveals edema-like changes not only subcutaneously, but also in muscle tissue after femoropopliteal bypass surgery. AB - BACKGROUND: The pathophysiological mechanisms that induce postrevascularization edema after femoropopliteal bypass surgery are not completely understood. Reperfusion-associated injury to revascularized tissue and damage to lymphatic structures are both likely to play a role. Aim of this study was to study edema formation after peripheral bypass surgery with magnetic resonance imaging. MATERIALS AND METHODS: Nine patients suffering from severe peripheral arterial occlusive disease were subjected to magnetic resonance imaging scans before and 1 week after autologous femoropopliteal or femorocrural bypass surgery. RESULTS: A 12% increase in volume of the upper legs and an 11% increase in volume of the lower legs were measured in patients postoperatively. The increase of volume was largely due to expansion of the subcutaneous compartments: a 35% increase in the upper legs and a 41% increase in the lower legs. Edema in the upper legs was predominantly located medially at the site of the surgical wound. In contrast, edema in the lower legs was homogenously distributed around the entire leg circumference. The muscle compartment showed no significant change of volume. However, in the majority of patients, edema-like changes were seen in selected muscles as well after a peripheral bypass reconstruction. CONCLUSION: Swelling of the subcutaneous compartments is mainly responsible for the volume increases in upper and lower legs similar to lymphatic edema. In addition, in a majority of patients, edema-like changes in selected muscles were seen especially in the upper legs. Reperfusion-associated injury as a cause of these changes cannot be ruled out. PMID- 22050881 TI - Lower-limb ischemia in the young patient: management strategies in an endovascular era. AB - BACKGROUND: The aim of this paper is to review the potential role of endovascular interventions for young patients with lower-limb ischaemia. METHODS: A literature search was performed of PubMed and Medline databases using appropriate search terms and limits. Case reports, retrospective studies, and prospective studies evaluating treatment of lower-limb ischemia in patients aged <50 years were scrutinized. Articles published between 1966 and 2010 were included in this review. RESULTS: Premature atherosclerosis is likely to represent the commonest cause of lower-limb ischemia in patients aged <50 years, although the incidence of nonatherosclerotic causes such as popliteal entrapment syndrome, cystic adventitial disease, and arteritis in these patients is greater than in older patients. As with older patients, endovascular interventions may be beneficial for patients with symptoms secondary to atherosclerosis. At present, the perceived durability of open surgery may be more preferable to patients aged <50 years, but the development of new endovascular technology is challenging this view. Endovascular interventions such as catheter-directed thrombolysis have specific roles in the treatment of lower-limb ischemia due to nonatherosclerotic causes. CONCLUSION: The use of angioplasty and stenting procedures to treat young patients with lower-limb ischemia is increasing and has specific roles. However, many developmental causes and nonatherosclerotic conditions still require primary surgical correction. PMID- 22050882 TI - Funnel technique for EVAR: "a way out" for abdominal aortic aneurysms with ectatic proximal necks. AB - BACKGROUND: To describe an endovascular technique for proximal stent-graft fixation in patients with an abdominal aortic aneurysm and an ectatic aortic neck. METHODS: We describe a method in which using currently available devices in a hybrid assembly offers another option for circumventing the limitations of problematic proximal fixation. CONCLUSIONS: Through four examples, we illustrate the feasibility of placing a straight endograft as proximal extension of a bifurcated or aorto-uni-iliac graft in patients with a dilated proximal aortic neck. It appears secure and effective, with no type I endoleak or migration over a midterm follow-up. PMID- 22050883 TI - Endovascular treatment for acute aortic syndrome. AB - BACKGROUND: The term "acute aortic syndrome" (AAS) includes conditions of high mortality, such as ruptured aneurysm, pseudoaneurysm and, aortic dissection. Open surgery for these cases has demonstrated unsatisfactory results, and endovascular treatment has become an excellent alternative. METHODS: We performed a retrospective review of patients with AAS who underwent endovascular treatment in our emergency department from July 2009 to February 2011. They represent 64% (16 of 25) of all patients with AAS seen during this period. RESULTS: Sixteen patients underwent endovascular treatment: eight ruptured aneurysms, six aortic dissections, one nonruptured painful aneurysm, and one pseudoaneurysm. No intramural hematoma or penetrating atherosclerotic ulcer was found. The mean age was 64.3 years, and arterial hypertension (100%) and smoking (64.7%) were the major comorbidities. Technical success rate was 93%, and overall 30-day mortality was 6.25%. CONCLUSION: Endovascular treatment for AAS was feasible. Technical success, 30-day mortality, hospital stay, and procedure time were similar to those of the other series reported in the literature, and the endovascular approach has became the main technique for AAS in our hospital. PMID- 22050884 TI - Surgical treatment of renal artery compression by diaphragmatic crus. AB - Symptomatic compression of the renal artery by the diaphragmatic crus is a rare disorder. To our knowledge, renal artery compression by the diaphragmatic crus complicated with poststenosis aneurysm has not been reported. We present the case of a 28-year-old man with refractory hypertension. Extrinsic compression of the bilateral renal arteries and celiac artery and the aneurysm were proven by surgical exploration. We successfully performed left renal artery revascularization and renal autotransplantation in situ. Normal perfusion of the two bypass graft vessels was proven by computed tomography angiography. PMID- 22050885 TI - Early protein malnutrition disrupts cerebellar development and impairs motor coordination. AB - Maternal malnutrition affects every aspect of fetal development. The present study asked the question whether a low-protein diet of the mother could result in motor deficits in the offspring. Further, to examine whether cerebellar pathology was correlated with motor deficits, several parameters of the postnatal development of the cerebellum were assayed. This is especially important because the development of the cerebellum is unique in that the time scale of development is protracted compared with that of the cortex or hippocampus. The most important result of the study is that animals born to protein-deficient mothers showed significant delays in motor development as assessed by rotarod and gait analysis. These animals also showed reduced cell proliferation and reduced thickness in the external granular layer. There was a reduction in the number of calbindin positive Purkinje cells (PC) and granular cells in the internal granular layer. However, glial fibrillary acidic protein-positive population including Bergmann glia remained unaffected. We therefore conclude that the development of the granular cell layer and the PC is specifically prone to the effects of protein malnutrition potentially due to their protracted developmental period from approximately embryonic day 11 to 13 until about the third postnatal week. PMID- 22050886 TI - Adamantane-platinum conjugate hosted in beta-cyclodextrin: enhancing transport and cytotoxicity by noncovalent modification. AB - This work reports the synthesis of a complex of a carboplatin analog having tethered adamantane that is encapsulated in the hydrophobic cavity of beta cyclodextrin (betaCD) and its cytotoxic activity towards human neuroblastoma cells (SK-N-SH). We found that this inclusion complex of betaCD adamantane carboplatin analog exhibited higher cytotoxicity towards SK-N-SH cells than carboplatin itself, and the inclusion complex exhibited a higher binding to plasmid pBR322 deoxyribonucleic acid (DNA) than carboplatin. Confocal fluorescence images of SK-N-SH cells treated with betaCD having an attached fluorescein isothiocyanate (FITC)-tag exhibited fluorescence in the vicinity of the nuclei of the neuroblastoma cells. Direct measurements of the platinum content in SK-N-SH cells using inductively coupled plasma mass spectrometry (ICP MS) indicated that the uptake rate of carboplatin was about 4 times higher than betaCD adamantane carboplatin analog inclusion complex. When compared to carboplatin, we believe that the higher cytotoxicity of inclusion complex towards SK-N-SH cells is due to its higher DNA binding ability as compared to carboplatin, and more efficient delivery to the nucleus of the cell. This work suggests that the advantage of deliberate noncovalent modification with betaCD through host-guest chemistry may also be broadly applicable to other anticancer agents as well. PMID- 22050887 TI - PET imaging using 64Cu-labeled sulfophthalocyanines: synthesis and biodistribution. AB - Sulfonated metallo phthalocyanines (MPcS(n)) are second generation photosensitizers advanced for photodynamic therapy of various medical applications. A series of ZnPcS(n) was demetallated and subsequently converted to the corresponding [(64)Cu]CuPcS(n) in 40-50% isolated yields and >98% radiochemical purities. Tumor-bearing mice were injected with the (64)Cu-labeled products and subjected to 3-h dynamic PET imaging studies. Biodistribution patterns showed characteristic differences between the various derivatives. Tumor uptake was detected only for the amphiphilic derivatives [(64)Cu]CuPcS(2) and [(64)Cu]CuPcS(3)C(6) (1-1.5%ID/g). The biological data suggest that PET imaging with [(64)Cu]CuPc can be used to establish structure-PDT efficacy relationships for Pc-based photosensitizers. PMID- 22050888 TI - beta-PNA: peptide nucleic acid (PNA) with a chiral center at the beta-position of the PNA backbone. AB - Peptide nucleic acid (PNA) monomers with a methyl group at the beta-position have been synthesized. The modified monomers were incorporated into PNA oligomers using Fmoc chemistry for solid-phase synthesis. Thermal denaturation and circular dichroism (CD) studies have shown that PNA containing the S-form monomers was well suited to form a hybrid duplex with DNA, whose stability was comparable to that of unmodified PNA-DNA duplex, whereas PNA containing the R-form monomers was not. PMID- 22050889 TI - Tumor bombesin analog loaded long-circulating and pH-sensitive liposomes as tool for tumor identification. AB - Long-circulating and pH-sensitive liposomes trapping (99m)Tc-HYNIC-betaAla bombesin((7-14)) (aSpHL-(99m)Tc-BBN((7-14))) were successfully prepared. Biodistribution studies and scintigraphic images were performed in Ehrlich tumor bearing Swiss mice. This system showed high accumulation in tumor tissue with high tumor-to-muscle ratio. Therefore, aSpHL-(99m)Tc-BBN((7-14)) could be considered as a potential agent for tumor diagnosis. PMID- 22050890 TI - [Diagnosis and therapy of cutaneous and mucocutaneous Leishmaniasis in Germany]. AB - The incidence of cutaneous and mucocutaneous Leishmaniasis (CL/MCL) is increasing globally, also in Germany, although the cases are imported and still low in number. The current evidence for the different therapies has many limitations due to lack of sufficient studies on the different Leishmania species with differing virulence. So far there is no international gold standard for the optimal management. The aim of the German joint working group on Leishmaniasis, formed by the societies of Tropical Medicine (DTG), Chemotherapy (PEG) and Dermatology (DDG), was to establish a guideline for the diagnosis and treatment of CL and MCL in Germany, based on evidence (Medline search yielded 400 articles) and, where lacking, on consensus of the experts. As the clinical features do not necessarily reflect the involved Leishmania species and, as different parasite species and even geographically distinct strains of the same species may require different treatments or varying dosages or durations of therapy, the guidelines suggest for Germany to identify the underlying parasite prior to treatment. Because of relevant differences in prognosis and ensuing therapy species should be identified in i) New World CL/MCL (NWCL/ MCL) to distinguish between L. mexicana complex and subgenus Viannia, ii) in suspected infections with L. mexicana complex to distinguish from L. amazonensis, and iii) in Old World CL (OWCL) to distinguish between L. infantum and L. major, L. tropica, or L. aethiopica. A state-of-the-art diagnostic algorithm is presented. For recommendations on localized and systemic drug treatment and physical procedures, data from the accessible literature were adjusted according to the involved parasite species and a clinical differentiation into uncomplicated or complex lesions. Systemic therapy was strictly recommended for i) complex lesions (e. g. > 3 infected lesions, infections in functionally or cosmetically critical areas such as face or hands, presence of lymphangitis), ii) lesions refractory to therapy, iii) NWCL by the subgenus Viannia or by L. amazonensis, iv) in MCL and v) in recalcitrant, or disseminating or diffuse cutaneous courses. In e. g. infection with L. major it encompasses miltefosine, fluconazole and ketoconazole, while antimony or allopurinol were here considered second choice. Local therapy was considered appropriate for i) uncomplicated lesions of OWCL, ii) L. mexicana-complex and iii) pregnant women. In e. g. infection with L. major it encompasses perilesional antimony, combined with cryotherapy, paromomycin 15 %/in methylbenzethoniumchlorid 12 % and thermotherapy. The group also stated that there is an urgent need for improving the design and the way of publishing of clinical trials in leishmaniasis. PMID- 22050891 TI - Exploring implementation of the 2010 Institute of Medicine's Child and Adult Food Care Program recommendations for after-school snacks. AB - OBJECTIVE: The aim of the present study was to explore the implementation of nutrition recommendations made in the 2010 Institute of Medicine (IOM) report, Child and Adult Care Food Program: Aligning Dietary Guidance for All, in school based after-school snack programmes. DESIGN: A descriptive study. SETTING: One large suburban school district in Minneapolis, Minnesota, USA. SUBJECTS: None. RESULTS: Major challenges to implementation included limited access to product labelling and specifications inconsistent with the IOM's Child and Adult Care Food Program (CACFP) recommendations, limited access to healthier foods due to current school district buying consortium agreement, and increased costs of wholegrain and lower-sodium foods and pre-packaged fruits and vegetables. CONCLUSIONS: Opportunities for government and industry policy development and partnerships to support schools in their efforts to promote healthy after-school food environments remain. Several federal, state and industry leadership opportunities are proposed: provide product labelling that makes identifying snacks which comply with the 2010 IOM CACFP recommended standards easy; encourage compliance with recommendations by providing incentives to programmes; prioritize the implementation of paperwork and technology that simplifies enrollment and accountability systems; and provide support for food safety training and/or certification for non-food service personnel. PMID- 22050892 TI - Insights into fruit function from the proteome of the hypanthium. AB - Apple (Malus*domestica Borkh.) was used as a model to studying essential biological processes occurring in mature fruit hypanthium, commonly referred to as the fruit flesh or pulp, a highly active tissue where numerous metabolic processes such as carbohydrate metabolism and signal transduction occur. To understand the complex biological processes occurring in the hypanthium, a proteomics approach was used to analyze the proteome from freshly harvested ripe apple fruits. A total of 290 well-resolved spots were detected using two dimensional gel electrophoresis (2-DE). Out of these, 216 proteins were identified representing 116 non-redundant proteins using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and either the MASCOT or ProteinProspector engine for peptide mass fingerprinting (PMF) database searching. Identified proteins were classified into 13 major functional categories. Among these, the energy metabolism class was the most represented and included 50% of proteins homologous to Arabidopsis proteins that are involved in the response to biotic and abiotic stresses, suggesting a dual role for these proteins in addition to energy metabolism. We also identified dynein heavy chain in the hypanthium although this protein has been proposed as absent from angiosperms and thus suggest that the lack of dyneins in higher plants studied to date may not be a general characteristic to angiosperm genomic organisation. We therefore conclude that the detection and elucidation of the apple hypanthium proteome is an indispensable step towards the comprehension of fruit metabolism, the integration of genomic, proteomic and metabolomic data to agronomic trait information and thus fruit quality improvements. PMID- 22050893 TI - Discovering the role of mitochondria in the iron deficiency-induced metabolic responses of plants. AB - In plants, iron (Fe) deficiency-induced chlorosis is a major problem, affecting both yield and quality of crops. Plants have evolved multifaceted strategies, such as reductase activity, proton extrusion, and specialised storage proteins, to mobilise Fe from the environment and distribute it within the plant. Because of its fundamental role in plant productivity, several issues concerning Fe homeostasis in plants are currently intensively studied. The activation of Fe uptake reactions requires an overall adaptation of the primary metabolism because these activities need the constant supply of energetic substrates (i.e., NADPH and ATP). Several studies concerning the metabolism of Fe-deficient plants have been conducted, but research focused on mitochondrial implications in adaptive responses to nutritional stress has only begun in recent years. Mitochondria are the energetic centre of the root cell, and they are strongly affected by Fe deficiency. Nevertheless, they display a high level of functional flexibility, which allows them to maintain the viability of the cell. Mitochondria represent a crucial target of studies on plant homeostasis, and it might be of interest to concentrate future research on understanding how mitochondria orchestrate the reprogramming of root cell metabolism under Fe deficiency. In this review, I summarise what it is known about the effect of Fe deficiency on mitochondrial metabolism and morphology. Moreover, I present a detailed view of the possible roles of mitochondria in the development of plant responses to Fe deficiency, integrating old findings with new and discussing new hypotheses for future investigations. PMID- 22050894 TI - The morphology of the pecten oculi in the common buzzard (Buteo buteo). AB - OBJECTIVE: The pecten oculi are an intraocular, vascular, and pigmented structure peculiar to the avian eye. In this study, we investigated the pecten oculi of the common buzzard (Buteo buteo) using stereomicroscopy and light and scanning electron microscopy (SEM). PROCEDURES: Twenty eyes from 10 adult buzzards were studied. Specimens from each buzzard were preserved in 10% buffered formalin and observed stereomicroscopically before being embedded in paraffin, sectioned, and stained with three stains: Mallory's triple staining technique as modified by Crossman, Hematoxylin-Eosin (HE), and Safranin O, and for examination by light microscopy. Specimens from two buzzards were also prepared for SEM. RESULTS: Stereomicroscopy and SEM examination showed the pecten oculi in the common buzzard to be pleated-consisting of 17-18 100 MUm thick folds. These folds are connected to one another by bands of connective tissue extending vertically between the plications. Blood vessels, approximately 30-40 MUm in diameter, were seen on the surface of the each fold. These vessels arise from the base of pecten, becoming thinner toward the apical end of the structure. A network of capillary vessels at the base of the plicated structure resembles contour lines. At high amplification, melanin granule accumulations were observed around the vascular structures of the plica on SEM images. Light microscopy supported the SEM observations. CONCLUSIONS: These findings reveal that the pecten oculi in the common buzzard are plicated and are remarkably similar to that of the other diurnal raptors. PMID- 22050895 TI - Pseudotumour cerebri in children: etiological, clinical features and treatment modalities. AB - To investigate the etiological and clinical features of pseudotumour cerebri (PTC) in children, features of 12 children with PTC were documented. The etiology could be clarified in 6 patients. The other 6 patients were accepted as idiopathic intracranial hypertension (primary PTC). Acetazolamide was used as the first drug and was effective in only 4 patients who had no underlying cause. Repeated lumbar punctures (LP) were performed in 6 patients and 5 of them were unresponsive. Prednisone was used in 3 patients and was effective in only one patient. The CSF pressure continued to be high in five patients and could be normalized only by withdrawing of the precipitating drug in three patients and by ventricular-peritoneal shunting in two patients with cerebral venous thrombosis. Although, medical treatment and repeated LP are usually effective in children with PTC, clarifying and solving the underlying cause can be crucial. PMID- 22050896 TI - Effect of short-term diphenhydramine administration on aqueous tear production in normal dogs. AB - OBJECTIVE: To perform a randomized, placebo-controlled, masked clinical trial using a cross-over design to determine the effect of oral diphenhydramine on aqueous tear production in normal dogs. ANIMALS STUDIED: Seventeen dogs with normal ophthalmic examinations. PROCEDURES: Baseline tear production was established for each dog by performing Schirmer tear test I (STT I). Dogs received 20-day treatment courses of both oral diphenhydramine and placebo solutions with a 10-day washout period between treatment periods. Each dog was randomly assigned to receive diphenhydramine or placebo at the outset of the study. Measurements of STT I values were measured at regular intervals during the study and were conducted at the same time of day throughout the study to control for diurnal variations in tear production. The significance of the impact of diphenhydramine treatment on the quantity of aqueous tear production, as determine by STT results over time, was evaluated using regression analysis with appropriate transformation. RESULTS: Statistical comparisons at each measurement time, including baseline measurements between control and treatment groups, revealed no significant differences. Mean STT I levels also did not differ significantly at any measurement time compared to baseline for treatment or control groups. CONCLUSIONS: Short-term administration of oral diphenhydramine does not result in a significant decrease in aqueous tear production in normal dogs. PMID- 22050897 TI - Philosophy and epidemiology. PMID- 22050898 TI - Strong nuclear EGFR expression in colorectal carcinomas is associated with cyclin D1 but not with gene EGFR amplification. AB - BACKGROUND: Prognostic and predictive significance of epidermal growth factor receptor (EGFR) in colorectal carcinomas (CRCs) is still controversial. The aim of the present study was to explore and correlate membrane and nuclear EGFR and cyclin-D1 protein expression with EGFR gene status of tumor cells. METHODS: Immunohistochemical and FISH analysis was performed on 135 archival formalin fixed and paraffin embedded CRCs. RESULTS: Strong membrane and strong nuclear EGFR staining was detected in 16% and 57% of cases, respectively, and strong cyclin-D1 expression in 57% samples. Gene EGFR amplification was identified in 5.9% and polysomy in 7.4% of cases, while 87% showed no EGFR gene changes. A statistically significant difference was only found between tumor grade and expression of membrane EGFR, while nuclear EGFR and cyclin-D1 expression was not associated with the clinicopathologic characteristics analyzed. Tumor cells displaying gene amplification and strong protein membrane EGFR expression overlapped, while EGFR gene status showed no correlation with nuclear EGFR and cyclin-D1. There was no association between membrane EGFR and cyclin-D1, whereas nuclear EGFR expression was strongly related to cyclin-D1 expression. CONCLUSIONS: Study results revealed heterogeneity among CRCs, which could have a predictive value by identifying biologically and probably clinically different subsets of tumors with the possibly diverse response to anti-EGFR therapies. PMID- 22050899 TI - Opportunities for primary and secondary prevention of excess gestational weight gain: General Practitioners' perspectives. AB - BACKGROUND: The impact of excess gestational weight gain (GWG) on maternal and child health outcomes is well documented. Understanding how health care providers view and manage GWG may assist with influencing healthy gestational weight outcomes. This study aimed to assess General Practitioner's (GPs) perspectives regarding the management and assessment of GWG and to understand how GPs can be best supported to provide healthy GWG advice to pregnant women. METHODS: Descriptive qualitative research methods utilising semi - structured interview questions to assess GPs perspectives and management of GWG. GPs participating in shared antenatal care in Geelong, Victoria and Sydney, New South Wales were invited to participate in semi - structured, individual interviews via telephone or in person. Interviews were digitally recorded and transcribed verbatim. Data was analysed utilising thematic analysis for common emerging themes. RESULTS: Twenty eight GPs participated, 14 from each state. Common themes emerged relating to awareness of the implications of excess GWG, advice regarding weight gain, regularity of gestational weighing by GPs, options for GPs to seek support to provide healthy lifestyle behaviour advice and barriers to engaging pregnant women about their weight. GPs perspectives concerning excess GWG were varied. They frequently acknowledged maternal and child health complications resulting from excess GWG yet weighing practices and GWG advice appeared to be inconsistent. The preferred support option to promote healthy weight was referral to allied health practitioners yet GPs noted that cost and limited access were barriers to achieving this. CONCLUSIONS: GPs were aware of the importance of healthy GWG yet routine weighing was not standard practice for diverse reasons. Management of GWG and perspectives of the issue varied widely. Time efficient and cost effective interventions may assist GPs in ensuring women are supported in achieving healthy GWG to provide optimal maternal and infant health outcomes. PMID- 22050900 TI - New approaches to in vitro diagnosis of hepatitis C infection a reason for post transfusion hepatitis: Diagnostic value of determination of hepatitis C virus core antigen. AB - In between the dates of February 2008-March 2009, by applying to Istanbul University CTF Microbiology and Clinical Microbiology Basic Sciences Branch and Duzen laboratories, 123 cases, where HCV RNA and anti-HCV positivity are identified with molecular (real-time PCR) and serologic (ELISA) methods as a positive control group, and 48 cases where HCV RNA and anti-HCV negativity are identified as a negative control group are established. The values of sensitivity, specificity, positive and negative approximation of recently developed HCV Core Ag (Abbott Diagnostics, Germany) kit are determined successively as 94.3%, 97.9%, 99.1%, 87%, 95.3% and 88%. Although the new HCV Ag assay is clearly not sensitive enough to replace HCV NAT it may serve as a valuable tool in the HCV diagnostic algorithm as it is able to pick up a great majority of anti-HCV and HCV RNA positive samples, thus allowing a timely and less expensive serological diagnosis of an active HCV infection. This may be an advantage for labs that do not have access to PCR easily. PMID- 22050901 TI - Continuous renal replacement therapy and blood transfusions in treating patients with crush syndrome: 8 Case studies from the Wenchuan earthquake. AB - OBJECTIVE: We analyzed the efficacy of continuous renal replacement therapy (CRRT) combined with blood transfusion for patients with crush syndrome from an earthquake. METHODS: Eight patients with crush syndrome were included. CRRT were performed in six of eight patients with crush syndrome, and transfusion was performed in all eight patients. Routine blood tests, urea nitrogen, creatinine, blood coagulation function, electrolyte levels, and serum myoglobin were determined and analyzed. RESULTS: Two patients regained their health completely, four patients required amputation but recovered well, and two patients died. The total amount of red blood cells transfused in the eight cases was 521U (mean volume=68.25U). CRRT was performed 164 times in six patients (mean 27.33 times per person). The routine blood test results and coagulation and renal function parameters improved obviously (P<0.05) in the six surviving patients. CONCLUSIONS: Sufficient blood transfusion and early dialysis treatment effectively improved the conditions of patients with crush syndrome. PMID- 22050902 TI - Methods related to molecular virology. PMID- 22050903 TI - Localized colonic stem cell transplantation enhances tissue regeneration in murine colitis. AB - Many patients suffer from chronic gastrointestinal diseases characterized by chronic inflammation, increased intestinal permeability and visceral pain in which there is no definitive treatment. Adult stem cells have recently been used in various disease states to contribute wound-healing processes. In the current study we investigated the ability of intra-colonic adult stem cells application to heal colonic inflammation in IL-10(-/-) mice with active colitis. The aims of this study were to determine whether intra-colonic infusion of adult colonic stem cells (CSCs) (local stem cell transplantation): (i) restores intestinal permeability; (ii) attenuates visceral hypersensitivity; (iii) heals murine colitis. IL-10(-/-) mice with active colitis were transplanted with adult stem cells. Mice received either a single intracolonic infusion of CSCs or colonic epithelial cells. Two weeks after transplantation, we measured visceral hypersensitivity and intestinal permeability and correlated these with histological improvement of colitis. IL-10(-/-) mice that received stem cell transplantation showed histopathologic evidence of recovery from colitis. Improvement in colitis as graded by pathology scores correlated with restoration of intestinal permeability and decreased visceral hypersensitivity. Intra-colonic administration of CSCs is a potential therapeutic method for treating refractory symptoms in patients with chronic gastrointestinal diseases associated with chronic inflammation and visceral hypersensitivity. This method may be safer and should have far fewer side effects than systemic stem cell administration. PMID- 22050904 TI - Allogeneic peripheral blood stem cell and bone marrow transplantation for hematologic malignancies: meta-analysis of randomized controlled trials. AB - Peripheral blood stem cells have emerged as an alternative to bone marrow for allogeneic transplantation. To elucidate the advantages and disadvantages of research evidence related to the effects of allogeneic peripheral blood stem cells transplantation (PBSCT) and bone marrow transplantation (BMT) for hematological malignancies, we conducted a systematic review of the literature of randomized controlled trials comparing PBSCT to BMT. We systematically searched Cochrane Library, MEDLINE, EMBASE and CNKI up to May 2011. Two reviewers independently identified the eligible studies and assessed the methodological quality of included trials. The relevant data were extracted and analysed using RevMan 5.1. Ten trials totaling 1224 patients have been assessed. Pooled comparisons of studies of PBSCT and BMT found that the overall survival in PBSCT group was non-significantly different from that in BMT group [RR 0.92, 95% CI (0.80-1.07)]. The disease-free survival and relapse rate in PBSCT group were significantly different from that in BMT group [RR 0.67, 95% CI (0.52-0.86) and RR 0.51, 95% CI (0.34-0.76), respectively]. The number of days to reach the absolute neutrophil and platelet count were shorter with PBSCT. The rates of acute and chronic graft-versus-host disease (GVHD) in PBSCT group were significantly higher than that in the BMT group. The mortality in PBSCT group was non-significantly different from that in BMT group. We concluded that PBSCT was associated with a similar overall survival and mortality, improved disease-free survival and a decrease in relapse, faster engraftment, more GVHD when compared with BMT in transplantation for hematologic malignancies. PMID- 22050905 TI - Protocatechuic aldehyde protects against experimental sepsis in vitro and in vivo. AB - Recent studies have demonstrated that nuclear factor-kappaB (NF-kappaB) and high mobility group box 1 (HMGB1) are associated with the pathophysiology of sepsis. The present study was carried out to investigate the effects of protocatechuic aldehyde (PA) on an experimental model of sepsis induced by caecal ligation and puncture (CLP) in rats and to elucidate the potential mechanism in the cultured murine macrophage cell line, RAW264.7 cells. Treatment of RAW 264.7 cells with PA blocked TNF-alpha-induced NF-kappaB phosphorylation and decreased HMGB1 expression. Septic rats received doses of 50 mg of PA alone or plus Imipenem by intravenous bolus injection into the tail vein. The results showed that PA reduced serum levels of HMGB1 and triggering the receptor expressed on myeloid cells, it attenuated myeloperoxidase in the lung, liver and small intestine, while it up-regulated serum level of IL-10. Meanwhile, PA alone or plus Imipenem reduced CLP-induced lethality in septic rats. These data indicate that the anti septic effect of PA is mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. The protective effects of PA might block the inflammatory cascades through HMGB1 and NF-kappaB signalling pathway. Our studies enhance the case for the use of PA in sepsis, and PA therefore seems promising in the treatment of sepsis in human beings. PMID- 22050906 TI - Concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci. AB - OBJECTIVE: To report concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci and to document any correlation with equine recurrent uveitis (ERU). PROCEDURE: Records of 131 horses (241 eyes) examined at the University of Georgia Veterinary Teaching hospital from 2001 to 2010 were reviewed with either clinically normal fundi or depigmented punctate chorioretinal foci in the absence of other fundic pathology. Data collected included patient signalment, concurrent clinical ocular findings and follow-up information. Sex, presence of no other intraocular findings, presence of ERU, presence of cataracts, and presence of vitreal disease were compared between normal and foci groups using chi-squared analysis. Age and length of follow-up time were compared using a student's t-test. RESULTS: Ninety-one horses (167 eyes) with chorioretinal foci and forty horses (74 eyes) with clinically normal ocular fundi were examined. Fifty-eight (64%) horses with chorioretinal foci and 20 (50%) horses with clinically normal fundi had a normal intraocular examination. There was no significant difference in any of the criteria examined between groups. CONCLUSIONS: Horses with depigmented punctate chorioretinal foci, in the absence of other fundic pathology, are not more likely to have intraocular disease or ERU than horses with clinically normal ocular fundi. These findings suggest that depigmented punctate fundic foci in horses are not indicative of or associated with ERU. PMID- 22050907 TI - Inflammasomes as molecular mediators of inflammation and cancer: potential role in melanoma. AB - The inflammasome is a multi-protein complex that mediates immune responses to microbial, host, and environmental signals. When active, inflammasomes regulate caspase-1 activation and IL-1beta secretion. There is a strong link between inflammation and cancer, and IL-1beta is one of the major molecules involved in both of these disease processes. Here we review the role of inflammasomes in regulating IL-1beta secretion, and the impact of this pathway on cancer pathogenesis, with a focus on melanoma. This represents an exciting new area of research, and could potentially result in new targets for melanoma therapeutics in the future. PMID- 22050908 TI - PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer. AB - Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPARgamma inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects of the wildtype Pro-allele of PPARG Pro(12)Ala in alcohol related breast cancer. In transiently transfected cells, transcriptional activation by PPARgamma and the PPARgamma-PGC-1alpha complex was inhibited by ethanol. PPARgamma 12Ala-mediated transcription activation was not enhanced by PGC-1alpha, resulting in allele specific transcription activation by the PPARgamma 12Pro-PGC-1alpha complex. Our results suggest that PPARgamma and PGC-1alpha activity is an important determinant of alcohol related breast cancer. PMID- 22050909 TI - Nanoencapsulated anti-CK2 small molecule drug or siRNA specifically targets malignant cancer but not benign cells. AB - CK2, a pleiotropic Ser/Thr kinase, is an important target for cancer therapy. We tested our novel tenfibgen-based nanocapsule for delivery of the inhibitor 2 dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) and an siRNA directed against both CK2alpha and alpha' catalytic subunits to prostate cancer cells. We present data on the TBG nanocapsule itself and on CK2 inhibition or downregulation in treated cells, including effects on Nuclear Factor-kappa B (NF kappaB) p65. By direct comparison of two CK2-directed cargos, our data provide proof that the TBG encapsulation design for delivery of drugs specifically to cancer cells has strong potential for small molecule- and nucleic acid-based cancer therapy. PMID- 22050910 TI - Subcellular distribution of glutathione precursors in Arabidopsis thaliana. AB - Glutathione is an important antioxidant and has many important functions in plant development, growth and defense. Glutathione synthesis and degradation is highly compartment-specific and relies on the subcellular availability of its precursors, cysteine, glutamate, glycine and gamma-glutamylcysteine especially in plastids and the cytosol which are considered as the main centers for glutathione synthesis. The availability of glutathione precursors within these cell compartments is therefore of great importance for successful plant development and defense. The aim of this study was to investigate the compartment-specific importance of glutathione precursors in Arabidopsis thaliana. The subcellular distribution was compared between wild type plants (Col-0), plants with impaired glutathione synthesis (glutathione deficient pad2-1 mutant, wild type plants treated with buthionine sulfoximine), and one complemented line (OE3) with restored glutathione synthesis. Immunocytohistochemistry revealed that the inhibition of glutathione synthesis induced the accumulation of the glutathione precursors cysteine, glutamate and glycine in most cell compartments including plastids and the cytosol. A strong decrease could be observed in gamma glutamylcysteine (gamma-EC) contents in these cell compartments. These experiments demonstrated that the inhibition of gamma-glutamylcysteine synthetase (GSH1) - the first enzyme of glutathione synthesis - causes a reduction of gamma EC levels and an accumulation of all other glutathione precursors within the cells. PMID- 22050912 TI - The role of a membrane-bound glutathione transferase in the peroxynitrite-induced mitochondrial permeability transition pore: formation of a disulfide-linked protein complex. AB - We have previously shown that the mitochondrial membrane-bound glutathione transferase (mtMGST1) is activated via thiol modifications and contributes to the mitochondrial permeability transition (MPT) pore. In the present study we aimed to confirm the role of mtMGST1 in the oxidant peroxynitrite (PON)-induced MPT pore opening. PON induced the swelling of mitoplasts (inner membranes including the matrix) as well as of the mitochondria. The swelling was markedly suppressed by ADP [an adenine nucleotide translocator (ANT) ligand] and partially suppressed by cyclosporin A or by GST inhibitors (tannic acid, S-hexylglutathione). Dithiothreitol (DTT), a disulfide bond-reducing reagent, prevented the swelling. Western blot analyses of mitoplast proteins after PON-induced swelling positively identified the high molecular weight protein (HMP) including mtMGST1 (monomer), ANT (48kDa), and cyclophilin D (CypD, 30kDa). The HMP level was decreased according to suppression of the swelling and undetectable after DTT treatment. The HMP formation and swelling were also suppressed by a Ca(2+) chelating agent and antioxidants. These results suggest that the HMP is a disulfide-linked protein complex involving mtMGST1, ANT, CypD and function as a MPT pore in PON induced swelling, in which the Ca(2+) released by PON might play an important role in the complex formation. PMID- 22050911 TI - Costs and cost-effectiveness of malaria control interventions--a systematic review. AB - BACKGROUND: The control and elimination of malaria requires expanded coverage of and access to effective malaria control interventions such as insecticide-treated nets (ITNs), indoor residual spraying (IRS), intermittent preventive treatment (IPT), diagnostic testing and appropriate treatment. Decisions on how to scale up the coverage of these interventions need to be based on evidence of programme effectiveness, equity and cost-effectiveness. METHODS: A systematic review of the published literature on the costs and cost-effectiveness of malaria interventions was undertaken. All costs and cost-effectiveness ratios were inflated to 2009 USD to allow comparison of the costs and benefits of several different interventions through various delivery channels, across different geographical regions and from varying costing perspectives. RESULTS: Fifty-five studies of the costs and forty three studies of the cost-effectiveness of malaria interventions were identified, 78% of which were undertaken in sub-Saharan Africa, 18% in Asia and 4% in South America. The median financial cost of protecting one person for one year was $2.20 (range $0.88-$9.54) for ITNs, $6.70 (range $2.22-$12.85) for IRS, $0.60 (range $0.48-$1.08) for IPT in infants, $4.03 (range $1.25-$11.80) for IPT in children, and $2.06 (range $0.47-$3.36) for IPT in pregnant women. The median financial cost of diagnosing a case of malaria was $4.32 (range $0.34-$9.34). The median financial cost of treating an episode of uncomplicated malaria was $5.84 (range $2.36-$23.65) and the median financial cost of treating an episode of severe malaria was $30.26 (range $15.64-$137.87). Economies of scale were observed in the implementation of ITNs, IRS and IPT, with lower unit costs reported in studies with larger numbers of beneficiaries. From a provider perspective, the median incremental cost effectiveness ratio per disability adjusted life year averted was $27 (range $8.15-$110) for ITNs, $143 (range $135 $150) for IRS, and $24 (range $1.08-$44.24) for IPT. CONCLUSIONS: A transparent evidence base on the costs and cost-effectiveness of malaria control interventions is provided to inform rational resource allocation by donors and domestic health budgets and the selection of optimal packages of interventions by malaria control programmes. PMID- 22050913 TI - Merkel cell carcinoma induces lymphatic microvessel formation. AB - BACKGROUND: Merkel cell carcinoma (MCC) is a rare, highly malignant neuroendocrine tumor of the skin characterized by frequent lymphatic metastasis. OBJECTIVE: We sought to identify lymphovascular anatomy and expression profiles of lymphangiogenic cytokines to give an opinion on lymphangiogenesis in MCC. METHODS: We studied lymphatic microanatomy and lymphangiogenic cytokines in 27 MCC by immunohistology or immunofluorescence (D2-40, lymphatic vessel endothelial hyaluronan receptor [LYVE-1], vascular endothelial growth factor [VEGF] receptor 3, VEGF-C, VEGF-D, Ki67/MiB-1, CD68/PG-M1, CD68/KP1, CD163), Merkel cell polyomavirus-specific polymerase chain reaction, and coanalysis with clinical and histologic data. RESULTS: We found a more than 3-fold increase in the mean density of absolute numbers of small lymphatic capillaries (diameter <10 MUm) and a more than 8-fold increase in the median ratio of the number of small to large lymphatics (<10/>=10 MUm) paratumorally compared with intraindividual controls. VEGF-C(+)CD68(+) CD163(+) cells (interpreted as M2 macrophages) could be identified as an important potentially lymphangiogenesis-inducing cell type. LIMITATIONS: Partially lacking follow-up data limited the analysis of the prognostic impact. CONCLUSIONS: Our findings strongly indicate lymphangiogenesis in MCC driven by VEGF-C(+)CD68(+) CD163(+) M2 macrophages. PMID- 22050914 TI - Nonbullous neutrophilic lupus erythematosus: a newly recognized variant of cutaneous lupus erythematosus. AB - BACKGROUND: Neutrophils in the setting of systemic lupus erythematosus (SLE) are commonly associated with bullous disease. Rare cases of nonbullous neutrophilic lesions have been reported in patients with SLE. OBJECTIVE: This study used clinical and histologic findings of 4 patients to further define the newly emerging entity of nonbullous neutrophilic lupus erythematosus (LE). METHODS: We reviewed the clinical and pathological findings of 4 patients with known SLE who developed urticarial papules, plaques, subcutaneous nodules, or a combination of these. RESULTS: All patients were women with established SLE. Histopathological findings in all patients included an interstitial and perivascular neutrophilic infiltrate with leukocytoclasia, and variable vacuolar alteration along the dermoepidermal junction. Direct immunofluorescence study results in two patients were positive for C3, IgG, and IgM along the basement membrane zone. One patient also presented with neutrophil-rich lupus panniculitis. All clinical lesions resolved with immunomodulating/immunosuppressive agents. LIMITATIONS: This study was limited by the small number of cases. CONCLUSIONS: Nonbullous neutrophilic LE is an important entity to consider in the differential diagnosis of neutrophil mediated eruptions. In addition, the histologic finding of neutrophils in the setting of lupus should alert one to the possibility of systemic disease. PMID- 22050915 TI - Effects of intravenous administration of dexmedetomidine on intraocular pressure and pupil size in clinically normal dogs. AB - OBJECTIVE: To evaluate the effects of the intravenous administration of dexmedetomidine on the intraocular pressure (IOP) and pupil size (PS) in normal dogs. ANIMALS STUDIED: Forty-two animals with no ocular abnormalities were included in this study. PROCEDURE: Following initial readings (T(0)) of IOP and PS, the dogs received an intravenous injection of dexmedetomidine (5 MUg/kg). Both measurements were repeated 10 min (T(10) ) and 20 min (T(20)) later. RESULTS: There were no significant differences in IOP measurements between T(0) and T(10), although a significant decrease was observed at T(20). A significant miosis was found in the first 10 min after sedation. At T(20), the PS slightly increased, resulting in no statistical differences with T(0) and T(10). CONCLUSION: Dexmedetomidine is an excellent option for surgery or diagnostic ocular procedures in dogs when a specific control of IOP is required. However, it must be used in combination with mydriatics in ophthalmic surgical or diagnostic procedures, which require complete dilation of the pupil. PMID- 22050916 TI - Prevalence and risk factors for self-reported diabetes among adult men and women in India: findings from a national cross-sectional survey. AB - OBJECTIVE: We examined the distribution of diabetes and modifiable risk factors to provide data to aid diabetes prevention programmes in India. DESIGN: Population-based cross-sectional survey of men and women included in India's third National Family Health Survey (NFHS-3, 2005-2006). SETTING: The sample is a multistage cluster sample with an overall response rate of 98 %. All states of India are represented in the sample (except the small Union Territories), covering more than 99 % of the country's population. SUBJECTS: Women (n 99 574) and men (n 56 742) aged 20-49 years residing in the sample households. RESULTS: Prevalence of diabetes was 1598/100 000 (95 % CI 1462, 1735) among men and 1054/100 000 (95 % CI 974, 1134) among women in India. Rural-urban and marked geographic variation were found with higher rates in south and north-eastern India. Weekly and daily fish intake contributed to a significantly higher risk of diabetes among both women and men. Risks of diabetes increased with increased BMI, age and wealth status of both women and men, but no effects of the consumption of milk/curd, vegetables, eggs, television watching, alcohol consumption or smoking were found. Daily consumption of pulse/beans or fruits was associated with a significantly reduced risk of diabetes among women, whereas non significant inverse associations were observed in the case of men. CONCLUSIONS: Prevalence was underestimated using self-reports. The wide variation in self reported diabetes is unlikely to be due entirely to reporting biases or access to health care, and indicates that modifiable risk factors exist. Prevention of diabetes should focus on obesity and target specific socio-economic groups in India. PMID- 22050917 TI - Protein levels in enteral feeds: do these meet requirements in children with severe cerebral palsy? AB - Children with cerebral palsy (CP) have been documented to have feeding difficulties, which increase in line with condition severity and result in lowered growth potential. Much nutrition literature surrounds energy intake and expenditure in these children, with less information available on other parameters such as protein and micronutrients, which are also important for growth and development. We examined differences in protein intake and a variety of protein metabolism indices in children with CP compared with controls. A total of twenty-four children aged 4-12 years with marked CP fed orally (O, n 15) or enterally (E, n 9) were recruited, including age-matched typically developing children (C, n 24). Fasting blood samples were analysed for levels of albumin, creatinine, urea and urate. Parents collected an exact food replica for three consecutive days of their child's actual intake, which were directly analysed for protein content. Significant differences were found in protein intakes between the groups (mean percentage minimum requirements: E = 178 (sd 47); O = 208 (sd 95); C = 311 (sd 119), P = 0.005). Despite all children consuming over recommended levels, children with CP had significantly reduced levels of the protein metabolic indices compared with controls. These include as z-scores: albumin mean C = 0.71 (sd 1.04) and CP = - 0.17 (sd 1.60), P = 0.03; creatinine C = - 2.06 (sd 0.46) and CP = - 3.11 (sd 0.98), P < 0.001; urate C = 0.18 (sd 0.62) and CP = - 0.58 (sd 0.93), P = 0.002. Post hoc analysis, the present data show potentially greater protein metabolism issues in enterally fed children, compared with the other groups. This may also support recent literature that suggests shortfalls in current recommendations. PMID- 22050918 TI - Effect of mydriasis induced by topical instillations of 0.5% tropicamide on the anterior segment in normotensive dogs using ultrasound biomicroscopy. AB - OBJECTIVE: To determine the effect of 0.5% tropicamide and the resultant mydriasis on the anterior segment in normotensive dogs using ultrasound biomicroscopy. PROCEDURE: Twenty-four dogs without ocular disease underwent ultrasound biomicroscopic examination of both the eyes under general anesthesia. Pharmacologic mydriasis was induced in the right eye of each dog by the topical instillation of 0.5% tropicamide. Ultrasound biomicroscopic examinations were performed and the anatomical parameters of the anterior segment were evaluated including the geometric iridocorneal angle (ICA) - formed by the plane of the iris root and the internal corneoscleral limbus - the width of the opening of the ciliary cleft (CC), the width of the mid-CC, the length of the CC, and the anterior chamber (AC) depth (distance between the corneal endothelium and the anterior lens capsule). RESULTS: Mydriasis resulting from the topical use of 0.5% tropicamide is associated with an increase in the geometric ICA and a decrease in the opening of the CC, without any effect on the width of the mid-CC, or on the length of the CC, or on the AC depth. CONCLUSIONS: Mydriasis induced by topical 0.5% tropicamide results in modification of the anterior segment which may influence the drainage of aqueous humor. PMID- 22050919 TI - Penetrating ocular gunshot injury in a Labrador Retriever. AB - A 31/2-year-old, female (spayed) working black Labrador Retriever was referred to the Unit of Comparative Ophthalmology at the Animal Health Trust after a penetrating lead gunshot injury to the right eye. Clinical examination revealed penetrating injuries to the right cornea, left lateral canthus, and left forelimb. Radiography revealed the presence of multiple metallic foreign bodies in the head and one in the left forelimb. B-mode ocular ultrasonography confirmed the presence of an intraocular metallic foreign body within the posterior tunics of the right eye. Medical treatment of the right eye over a period of 1 month resulted in a comfortable, visual eye. Long-term follow-up over 41/2 years revealed a slow deterioration in vision because of progressive lens opacification and the presence of a localized area of chorioretinopathy. PMID- 22050920 TI - Protocol: methodology for chromatin immunoprecipitation (ChIP) in Chlamydomonas reinhardtii. AB - We report on a detailed chromatin immunoprecipitation (ChIP) protocol for the unicellular green alga Chlamydomonas reinhardtii. The protocol is suitable for the analysis of nucleosome occupancy, histone modifications and transcription factor binding sites at the level of mononucleosomes for targeted and genome-wide studies. We describe the optimization of conditions for crosslinking, chromatin fragmentation and antibody titer determination and provide recommendations and an example for the normalization of ChIP results as determined by real-time PCR. PMID- 22050921 TI - Spin tagging for hyperpolarized 13C metabolic studies. AB - In studies utilizing pre-polarized (13)C substrates to investigate metabolic activities in vivo, the metabolite signals observed in a region or a voxel contains a mixture of intracellular and extracellular components. This extracellular component arriving via perfusion may confound the measurements of metabolic flux or exchange rates. But if spin tagging is performed on the magnetization of the substrate, it may be possible to measure the signals of the metabolic products in the intracellular space that were derived from the tagged substrate spins locally. In this study, a spin tagging pulse sequence designed for acquiring data from spatially tagged longitudinal magnetization in hyperpolarized (13)C metabolic studies was presented and tested. Using a spectral spatial RF pulse during the tagging preparation enabled the observation of metabolite signals derived exclusively from the tagged substrate in vivo. PMID- 22050922 TI - Protracted wound healing due to pro-inflammatory condition: an instance of antagonistic pleiotropy theory. PMID- 22050924 TI - Air pollution and anemia as risk factors for pneumonia in Ecuadorian children: a retrospective cohort analysis. AB - BACKGROUND: Ambient air pollution and malnutrition, particularly anemia, are risk factors for pneumonia, a leading cause of death in children under five. We simultaneously assessed these risk factors in Quito, Ecuador. METHODS: In 2005, we studied two socioeconomically similar neighborhoods in Quito: Lucha de los Pobres (LP) and Jaime Roldos (JR). LP had relatively high levels of air pollution (annual median PM2.5 = 20.4 MUg/m3; NO2 = 29.5 MUg/m3) compared to JR (annual median PM2.5 = 15.3 MUg/m3; NO2 = 16.6 MUg/m3). We enrolled 408 children from LP (more polluted) and 413 children from JR (less polluted). All subjects were aged 18-42 months. We obtained medical histories of prior physician visits and hospitalizations during the previous year, anthropometric nutrition data, hemoglobin levels, and hemoglobin oxygen saturation via oximetry. RESULTS: In anemic children, higher pollution exposure was significantly associated with pneumonia hospitalization (OR = 6.82, 95%CI = 1.45-32.00; P = 0.015). In non anemic children, no difference in hospitalizations by pollution exposure status was detected (OR = 1.04, NS). Children exposed to higher levels of air pollution had more pneumonia hospitalizations (OR = 3.68, 1.09-12.44; P = 0.036), total respiratory illness (OR = 2.93, 95% CI 1.92-4.47; P < 0.001), stunting (OR = 1.88, 1.36-2.60; P < 0.001) and anemia (OR = 1.45, 1.09-1.93; P = 0.013) compared to children exposed to lower levels of air pollution. Also, children exposed to higher levels of air pollution had significantly lower oxygen saturation (92.2% +/- 2.6% vs. 95.8% +/- 2.2%; P < 0.0001), consistent with air pollution related dyshemoglobinemia. CONCLUSIONS: Ambient air pollution is associated with rates of hospitalization for pneumonia and with physician's consultations for acute respiratory infections. Anemia may interact with air pollution to increase pneumonia hospitalizations. If confirmed in larger studies, improving nutrition related anemia, as well as decreasing the levels of air pollution in Quito, may reduce pneumonia incidence. PMID- 22050925 TI - Association of mannose-binding lectin gene polymorphism with tuberculosis susceptibility and sputum conversion time. AB - Mannose-binding lectin (MBL) plays an important role in innate immunity. The effect of low MBL levels producing variants of MBL2 gene on tuberculosis (TB) has been controversial with some studies reporting it to confer protection against the disease, whereas others estimating a susceptibility relation. Other than conducting a case-control study to evaluate the role of MBL A/B polymorphism on TB, we conducted a longitudinal study to check whether this MBL variant can influence the host response to Mycobacterium tuberculosis infection. A total of 357 TB patients (286 pulmonary TB, 71 extrapulmonary (EP) TB) and 392 healthy controls belonging to same ethnicity were included in the study. We found the mutant allele 'B' allele confers a protective role against TB in our study population. This effect was absent in EP patients. On stratification on the basis of sex, the protective role of the 'B' allele was found to be limited to females only and males reported no significant difference. No effect of MBL A/B polymorphism on sputum conversion time was reported. We conclude that MBL 'B' allele is associated with protection against TB, but no influence was found on sputum conversion rate. PMID- 22050926 TI - Prentiss orchiopexy applied in younger age group. AB - PURPOSE: To evaluate the efficacy and safety of the operative technique for the correction of cryptorchidism described by Prentiss in the 1950s, who conducted measurements on patients over 6 years of age, and on cadaveric specimens. We applied the technique in a younger age group. MATERIAL AND METHODS: We prospectively studied the results of 50 orchiopexies in children 8-59 months of age (mean 32.3 months), separated into three age groups: 8-18 (N=14), 19-36 (N=18), and 36-59 (N=18) months. The patients were selected for having their undescended testis in the inguinal canal and not reaching the scrotum after adequate inguinal and retroperitoneal dissection. We eliminated the anatomic angulation of the vas deferens and testicular vessels around the internal inguinal ring and inferior epigastric vessels, in order to improve distal scrotal positioning (Prentiss maneuver). We compared the position of the testis before and after the maneuver. We re-examined the children 1 year postoperatively for testicular position and quality. RESULTS: The average gain in scrotal positioning was 6-20 mm (mean 13 mm). At follow-up, 36 testes (78%) had retained a low scrotal position, 10 (20%) a middle scrotal position, and 4 (8%) presented in an upper scrotal position. CONCLUSIONS: The Prentiss maneuver is both safe and efficient when applied to the younger age group, in order to gain adequate intrascrotal cord length and to place the testis in a more distal scrotal position. PMID- 22050927 TI - Excretory/secretory antigens from Dirofilaria immitis adult worms interact with the host fibrinolytic system involving the vascular endothelium. AB - Dirofilaria immitis is the causative agent of canine and feline heartworm disease. The parasite can survive for long periods of time (7 years or more) in the circulatory system of immunocompetent reservoirs, producing usually a chronic inflammatory vascular disease. In addition, the simultaneous death of groups of adult worms can trigger an acute disease characterized by the exacerbation of inflammatory reactions and the emergence of serious thromboembolic events. In the context of the D. immitis/host relationships, the aim of this study was to investigate the interaction between the excretory/secretory antigens from D. immitis adult worms (DiES) and the fibrinolytic system of the host. Using an enzyme-linked immunosorbent assay we showed that DiES extract is able to bind plasminogen and generate plasmin, although this fact requires the presence of the tissue plasminogen activator (t-PA). Moreover, we established that DiES extract enhances t-PA expression in cultured vascular endothelial cells. Additionally, 10 plasminogen-binding proteins from DiES extract were identified by mass spectrometry (HSP60, actin-1/3, actin, actin 4, transglutaminase, GAPDH, Ov87, LOAG_14743, galectin and P22U). The data suggest that DiES antigens interact with the environment of the parasite regulating the activation of the fibrinolytic system of the host with involvement of the vascular endothelium in the process. PMID- 22050928 TI - Studies on the kinetics and equilibrium of the solvent extraction of chromium(III) from alkaline aqueous solutions of different composition in the system with Aliquat 336. AB - The kinetics and equilibrium of Cr(III) extraction with Aliquat 336 from the alkaline aqueous solutions containing anions of various complexing abilities and solvating properties, as: nitrates, or perchlorates, or sulphates, were studied and interpreted. Stoichiometry of Cr(III) complexes formed in the organic phases was also discussed. It was found that under the same conditions the yield and the rate of Cr(III) extraction as well as values of mass transfer coefficient increase in the following order of anions: perchlorates50%) after the first infusion and maintained at low levels throughout the treatment period. In contrast, in eight patients (16%) there was an early recovery of CD49d expression to pre-treatment levels related to NABs development. While three cases experienced hypersensitivity reactions, three others were identified solely on the basis of an undiminished level of CD49d, with neither infusion reaction nor clinical worsening. These 3 patients had very high levels of NAbs and no detectable serum natalizumab. Two additional patients had early but transient recovery of CD49d expression. These patients had low levels of transient Nabs and returned to significant CD49d inhibition after few natalizumab infusions. We suggest that monitoring of CD49d expression can be used as a surrogate biomarker of natalizumab efficiency. If the CD49d expression is sustained at pre-treatment levels, patients should be tested for persistent NAbs and considered for treatment interruption. PMID- 22050953 TI - Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): a misdiagnosed disease entity. AB - Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was originally described in a large Swedish pedigree. Since then, 22 reports describing a total of 13 kindreds and 11 sporadic cases have been published. Inheritance is autosomal dominant, albeit the gene is unknown. Here we report on the clinical findings, genealogical data, brain MRI data, and autopsy/biopsy findings of four probands from three independently ascertained novel families from Norway, Germany and US. We identified a 39-year-old female and her twin sister, a 52-year-old male and a 47-year-old male with progressive neurological illness characterized by personality changes, cognitive decline and motor impairments, such as gait problems, bradykinesia, tremor and rigidity. Brain MRI showed white matter abnormalities with frontal prominence. Brain biopsy/autopsies were consistent with HDLS. HDLS is an under-recognized disease and in reporting these cases, we aim to increase the awareness of the disorder. Due to varied and wide phenotypic presentations, which may imitate several neurodegenerative diseases, HDLS can be difficult to diagnose. Definitive diagnosis can be established only by direct brain tissue examination. Familiarity with the clinical presentation and typical neuroimaging findings may be helpful in narrowing the diagnosis. PMID- 22050955 TI - A new age for child protection--General Comment 13: why it is important, how it was constructed, and what it intends? AB - Children continue to be subjected to high levels of violence (i.e., physical, psychological and sexual maltreatment) throughout the world. International concern about violence against children has increased significantly during the last decade. A Study on Violence Against Children, encouraged by the UN Committee on the Rights of the Child, conducted under the auspices of the United Nations Secretary General and reported in 2006, has become a rallying call to improve child protection. Child protection practices and systems have been judged to be generally inadequate and, in some cases, destructive. It is widely recognized that business as usual-more of the same-will not do. A General Comment (guide to fulfilling obligations) for Article 19, the central conceptualization of child protection of the UN Convention on the Rights of the Child, has the potential to promote a worldwide reformulation of child protection priorities, policies, and practices by virtue of the infusion of a child rights approach. It can be a mechanism for framing and promoting the transformational change needed - for a genuine paradigm shift. Here, explication is given for the historical context, rationale, centrality of child rights, process of development, holistic nature, and primary elements of General Comment 13 (GC13): The child's right to freedom from all forms of violence. GC13 embodies and champions a child rights approach to child protection entailing strong support for proactive primary prevention, promotion of good child care, and a commitment to secure the rights and well being of all children. A child rights-based, comprehensive coordinating framework is recommended for the implementation of GC13. PMID- 22050954 TI - Cell-derived microparticles in atherosclerosis: biomarkers and targets for pharmacological modulation? AB - Cardiovascular diseases remain an important cause of morbi-mortality. Atherosclerosis, which predisposes to cardiovascular disorders such as myocardial infarction and stroke, develops silently over several decades. Identification of circulating biomarkers to evaluate cardiovascular event risk and pathology prognosis is of particular importance. Microparticles (MPs) are small vesicles released from cells upon apoptosis or activation. Microparticles are present in blood of healthy individuals. Studies showing a modification of their concentrations in patients with cardiovascular risk factors and after cardiovascular events identify MPs as potential biomarkers of disease. Moreover, the pathophysiological properties of MPs may contribute to atherosclerosis development. In addition, pharmacological compounds, used in the treatment of cardiovascular disease, can reduce plasma MP concentrations. Nevertheless, numerous issues remain to be solved before MP measurement can be applied as routine biological tests to improve cardiovascular risk prediction. In particular, prospective studies to identify the predictive values of MPs in pathologies such as cardiovascular diseases are needed to demonstrate whether MPs are useful biomarkers for the early detection of the disease and its progression. PMID- 22050956 TI - Developing a template for National Child Protection Index Reports. AB - OBJECTIVES: What impact does the strengthening of child rights have on the experience and circumstances of children? CRC General Comment 13 emphasizes that defining measurable targets for improvements in child protection is a key element of efforts to strengthen child rights and well-being across the world. This paper describes an attempt to identify key domains relevant to such mapping of child protection indicators, and the feasibility of collecting data-from existing data sources or otherwise-to complete a "National Child Protection Index Report" summarizing achievements and concerns at a national level. METHODS: A process of inter-agency consultation was facilitated by the CPC Learning Network to establish a template for the Index Report. The template was modeled on that used for the "Countdown to 2015" maternal, neonatal and child health initiative, aiming to capture indices not only of key protection risks but also implementation and coverage of key protection measures. The work drew on indicator development and policy initiatives by a number of international child protection agencies. The template developed was used as a basis to pilot national data collection in Indonesia and, at a sub-national level, in northern Uganda. FINDINGS: The template provides a concise summary of protection issues of relevance to a broad range of constituencies, global and national. However, in the pilot settings, existing routine data collection was inadequate to effectively populate a large proportion of indicators. Mechanisms of collating findings from discrete assessments-another potential source of data for completion of the index report-were also generally underdeveloped. PRACTICE IMPLICATIONS: In settings where state infrastructure allows the collection and analysis of routine data in such domains as health and economic activity, such efforts should be extended to the child protection sector. Discrete assessments by governmental or non-governmental agencies also provide significant potential for more effective sharing and collation of information. National Child Protection sub-clusters or equivalent structures can play an important role in facilitating both of these processes. PMID- 22050957 TI - Commentary: an approach to assessing "accountability" in implementing the UN Convention on the Rights of the Child. PMID- 22050958 TI - Intraocular pressure and Schirmer tear test results in clinically normal Long Eared Hedgehogs (Hemiechinus auritus): reference values. AB - OBJECTIVE: The present study was undertaken to establish reference values for Schirmer tear test (STT) and intraocular pressure (IOP) in the long-eared hedgehog (Hemiechinus auritus). ANIMALS: Fourteen healthy long-eared hedgehogs (H. auritus) of either sex were studied. PROCEDURES: The hedgehogs were individually immobilized with an intramuscular injection of combined Ketamine (20 mg/kg) and Diazepam (0.5 mg/kg), and each animal underwent ophthalmic examinations including: STT, tonometry, biomicroscopy, and indirect ophthalmoscopy. RESULTS: No significant effects of animal gender, weight, side (right vs. left eye) were found in this study. Mean (SD) STT values for all eyes (n = 28) were 1.7 +/- 1.2 mm/1 min with a range of 0-4 mm/1 min. Mean STT in male animals was 2.2 +/- 1.2. Mean STT in female Hedgehogs was 1.3 +/- 1.1. Mean (SD) IOP values by applanation tonometry were 20.1 +/- 4.0 mmHg (range 11.5-26.5 mmHg). Mean (SD) IOP values by applanation tonometry were 18.2 +/- 4.0 and 22.0 +/- 3.2 mmHg for males and females, respectively. CONCLUSIONS: This study reports STT and IOP findings in long-eared hedgehogs (H. auritus). PMID- 22050959 TI - Activation of satellite glial cells in lumbar dorsal root ganglia contributes to neuropathic pain after spinal nerve ligation. AB - The role of satellite glial cells (SGCs) of sensory ganglia in chronic pain begins to receive interest. The present study aims to investigate the contribution of SGC activation to the development of neuropathic pain. A neuropathic pain model was established by lumbar 5 spinal nerve ligation (SNL), and glial fibrillary acidic protein (GFAP) was used as a marker of SGC activation. It was found that SGCs were activated in the ipsilateral dorsal root ganglia (DRG) increased significantly as early as 4h following SNL, gradually increased to a peak level at day 7, and then stayed at a high level to the end of the experiment at day 56. SGC activation in the SNL group was significantly higher than that in the sham group at days 1, 3 and 7 after operation. Immunofluorescent double labeling showed that the activated SGCs encircled large, medium-sized and small neurons. The SGCs surrounded the small and medium-sized neurons were preferentially activated in the early phase, but shifted to large diameter neurons as time went on. Continuous infusion of fluorocitrate, a glial metabolism inhibitor, to the affected DRG via mini-osmotic pump for 7d significantly alleviated mechanical allodynia at day 7. These results suggest that SGCs in the DRG were activated after SNL. SGC activation contributed to the early maintenance of neuropathic pain. PMID- 22050960 TI - Metabolic gene expression changes in the hippocampus of obese epileptic male rats in the pilocarpine model of temporal lobe epilepsy. AB - Chronically epileptic male adult rats in the pilocarpine model of temporal lobe epilepsy (TLE), exhibited gross expansion of abdominal fat mass and significant weight gain several months after induction of status epilepticus (SE) when compared to control rats. We hypothesized that epileptogenesis can induce molecular changes in the hippocampus that may be associated with metabolism. We determined the expression levels of genes Hsd11b1, Nr3c1, Abcc8, Kcnj11, Mc4r, Npy, Lepr, Bdnf, and Drd2 that are involved in regulation of energy metabolism, in the hippocampus of age-matched control and chronic epileptic animals. Taqman based quantitative real time polymerase chain reaction (qPCR) and the delta-delta cycle threshold (CT) methods were used for the gene expression assays. Gene expression of Hsd11b1 (cortisol generating enzyme) was significantly higher in epileptic versus control rats at 24h and 2 months, after induction of SE. Nr3c1 (glucocorticoid receptor) mRNA levels on the other hand were down-regulated at 24h, 10 days and 2 months, post SE. Abcc8 (Sur1; subunit of ATP-sensitive potassium (K(ATP)) channel) was significantly down-regulated at 10 days post SE. Kcnj11 (Kir6.2; subunit of ATP-sensitive potassium (K(ATP)) channel) was significantly up-regulated at 24h, 1 month and 2 months post SE. Thus, we demonstrated development of obesity and changes in the expression of metabolic genes in the hippocampus during epileptogenesis in male rats in the pilocarpine model of TLE. PMID- 22050961 TI - Inhibition by dexmedetomidine of the activation of spinal dorsal horn glias and the intracellular ERK signaling pathway induced by nerve injury. AB - Activation of glial cells and the intracellular ERK signaling pathway plays an important role in the development and maintenance of neuropathic pain. As well as neurons, glial cell membranes also express alpha2-adrenergic receptors, but the effects of selective activation of these receptors on glial cell activation induced by neuropathic pain have yet to be clarified. We investigated the effects of intraperitoneal (IP) injections of tolerable doses of dexmedetomidine (DEX), a highly selective agonist of alpha2-adrenergic receptors, on activation of spinal dorsal root glial cells and the intracellular ERK signaling pathway induced by neuropathic pain. Adult rats that underwent partial sciatic nerve ligation (PNSL) were treated with repeated IP injections of DEX 20 MUg/kg or 40 MUg/kg, and their thermal and mechanical hyperalgesia thresholds were measured. The distribution and morphological changes of microglias and astrocytes were observed by immunofluorescence. Western blot was used to detect changes of glial fibrillary acid protein (GFAP) and pERK expression. Repeated IP injections of DEX 40 MUg/kg for 7 or 14 days markedly reduced the thermal and mechanical hyperalgesia induced by PSNL. In addition, DEX 20 MUg/kg for 14 days and 40 MUg/kg for 7 days also significantly inhibited PSNL-induced activation of pERK in the spinal dorsal horn. Thus, repeated IP injections of DEX can markedly relieve the hyperalgesia of neuropathic pain in rats. The analgesic effect of DEX may be attributed to its inhibition of glial cell hypertrophy in the spinal dorsal horn and activation of the intracellular ERK signaling pathway. PMID- 22050962 TI - Dentigerous cyst of inflammatory origin-a diagnostic dilemma. AB - Odontogenic cysts commonly encountered in dental practice are the radicular cysts and dentigerous cysts. Apart from the developmental origin of dentigerous cysts, an inflammatory origin has also been suggested. It has been reported that inflammation progressing from the root apex of the deciduous tooth brings about development of the dentigerous cyst around the unerupted permanent tooth. The aim of the present article is to report 4 additional cases of dentigerous cyst believed to be of inflammatory origin and to highlight the diagnostic dilemma in segregating both the entities. The 4 cases were of patients with a mixed dentition with the pathology related to the deciduous tooth present. Radiographically, pericoronal radiolucency was seen attached at the cementoenamel junction of impacted tooth and in continuation with lamina dura of deciduous tooth. Microscopically, the cystic cavity was lined by reduced enamel epithelium like lining, which was hyperplastic to anastomosing in areas in few cases. This study proposes the predicament in accurately diagnosing such cases. PMID- 22050963 TI - Distinct immunophenotype of early T-cell progenitors in T lymphoblastic leukemia/lymphoma may predict FMS-like tyrosine kinase 3 mutations. AB - FMS-like tyrosine kinase 3 (FLT3) mutation in T lymphoblastic leukemia/lymphoma (T-LL) is rare (~4%) and reported only in cases with CD117 expression. This study aimed to identify the immunophenotypic features that may predict FLT3 mutations. We report 3 (43%) of 7 CD117(+) T-LL cases harboring FLT3-internal tandem duplication mutation. Compared with 4 FLT3-unmutated cases, all 3 FLT3-mutated cases had a distinct immunophenotype (CD1a( )/CD2(+)/CD7(+)/CD34(+)/CD117(uniform+)/Tdt(+)) corresponding to the stage of earliest thymic T-cell progenitors possessing myeloid lineage potential. Indeed, all FLT3-mutated T-LL cases expressed myeloperoxidase on a very small subset of blasts and, thus, may be further considered a mixed phenotype acute leukemia, T/myeloid, by the 2008 World Health Organization classification scheme. We conclude that this unique immunophenotype (CD1a( )/CD2(+)/CD7(+)/CD34(+)/CD117(+)/Tdt(+)) is a better predictor of FLT3 mutation than sole CD117 expression. PMID- 22050964 TI - Pathologic complete response to neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma is associated with a better prognosis. AB - In patients with pancreatic ductal adenocarcinoma (PDA) who received neoadjuvant therapy and pancreatectomy, pathologic complete response (pCR) is rarely observed and the prognostic significance of pCR is not clear. In this study, we identified 11 patients with pCR (2.5%) from 442 patients with PDA who received neoadjuvant treatment and pancreatectomy from 1995 to 2010. There were 6 men and 5 women, with a median age of 61 years. Four patients had either synchronous or history of extrapancreatic cancer. Five patients received neoadjuvant chemotherapy followed by chemoradiation, and 6 received chemoradiation alone. Ten patients had pancreaticoduodenectomy, and 1 had distal pancreatectomy. Scar and chronic pancreatitis consistent with therapy effect were present in all cases (100%). Pancreatic intraepithelial neoplasia (PanIN) 3/carcinoma in situ was present in 5 cases, and PanIN1 and PanIN2 in 5 cases. However, no residual invasive carcinoma or lymph node metastasis was identified in all cases. Follow-up information was available in 10 patients. Follow-up time ranges from 6 to 194 months (median, 63 months). During the follow-up, 3 patients died of other causes, and 1 developed a second primary PDA in the tail of the pancreas at 84 months after the initial pancreaticoduodenectomy and died at 105 months after the initial diagnosis of PDA. The other 6 patients were alive with no evidence of disease. Patients with pCR had a better survival than did those who had posttherapy stage I or IIA disease (P < .001). Patients with PDA who received neoadjuvant therapy and had pCR in pancreatectomy are rare but have a better prognosis. PMID- 22050965 TI - Histology and distribution of prostatic tissue on prostatic urethral margins: evaluation of radical prostatectomy specimens and implications on frozen section analysis. AB - The identification of prostate-specific antigen (PSA)-producing glands in prostatic urethral margins is often challenging, especially when examined as intraoperative frozen sections. To assess the histology of periurethral prostatic urethral glands and their expression of PSA and cytokeratins 7 and 20, we examined prostatic urethras of frozen and permanent sections of radical prostatectomy specimens. We observed 3 types of prostatic urethral glands: urethral mucosal, prostatic acinar, and mixed. The urethral mucosal type consisted of a single layer of surface cuboidal to columnar cells with densely eosinophilic luminal cytoplasm and underlying urothelial cells. The prostatic acinar type was lined by prostatic-type secretory cells and basal cells. The mixed type showed luminal secretory cells and underlying urothelial cells. The gland types were correctly assigned in most frozen section slides. The proximal segment of the prostatic urethra and the bladder neck consisted mostly of the urethral mucosal type, whereas the distal segment and apical margins consisted mostly of the prostatic acinar type. Prostate-specific antigen was expressed in secretory cells in prostatic acinar and mixed types, whereas cytokeratin 7 was expressed by urothelial cells and surface cells of the urethral mucosal type. Cytokeratin 20 was not expressed in any of these cells. These results indicate that PSA-expressing cells are abundant in the distal segment of the prostatic urethra and apical margin and share histologic features of prostatic secretory cells. These PSA-expressing prostatic acinar and mixed-type glands should be reported as a potential source of PSA-secreting benign glands. PMID- 22050966 TI - Comparison of clarity of nucleocytoplasmic differentiation of oral tissues processed by microwave and conventional methods. AB - The microwave-assisted tissue processing is believed to have brought a revolutionary improvement in histopathology. The technique shortens the tissue processing time from hours to minutes. The technique is responsive to the patient and physician needs, improves the use of reagents while reducing or eliminating their toxicity, creates a personnel-friendly workflow, and places the laboratory in a better position to meet the demands of the rapidly expanding field of molecular medicine. This study was conducted to determine the efficacy of microwave tissue processing method for orofacial biopsy specimens by comparing 5 different protocols of microwave histoprocessing with the conventional method, based on the clarity of nucleocytoplasmic differentiation of tissues processed by each method. The current study demonstrated that different protocols of microwave histoprocessing can be achieved without a demonstrable decrease in section quality or interpretation. PMID- 22050968 TI - Efficacy of albendazole combined with a marine fungal extract (m2-9) against Angiostrongylus cantonensis-induced meningitis in mice. AB - The pathogenesis of angiostrongyliasis, resulting from Angiostrongylus cantonensis invasion of the human central nervous system, remains elusive. Anthelmintics are usually used to kill worms, although dead worms in the brain may cause severe inflammation which will lead to central nervous system damage. Therefore, combination therapy with anthelmintics and anti-inflammatory drugs in the treatment of human angiostrongyliasis needs further study. To evaluate the efficacy of albendazole combined with a marine fungal extract (m2-9) in A. cantonensis infection, BALB/c mice infected by the third-stage larvae of A. cantonensis were divided into three groups: mice treated with albendazole or m2-9 alone or in combination from day 5 post-inoculation (PI). Several efficacy parameters were recorded, including weight change, worm recovery, neurological function, behavioural analysis, eosinophil and leucocyte counts. The results showed that combination therapy increased body weight, reduced worm burden, improved learning ability, memory and action, decreased neurological dysfunction and leucocyte response in these mice. The combination of albendazole and m2-9 treatment significantly decreased leucocyte response and increased the frequency of rearing, compared to infected mice treated with either drug alone. Therefore, m2-9 is a natural product with potentially significant therapeutic value for angiostrongyliasis and is worthy of further study. PMID- 22050969 TI - Three-dimensional analysis by electron diffraction methods of nanocrystalline materials. AB - To analyze nanocrystalline structures quantitatively in 3D, a novel method is presented based on electron diffraction. It allows determination of the average size and morphology of the coherently scattering domains (CSD) in a straightforward way without the need to prepare multiple sections. The method is applicable to all kinds of bulk nanocrystalline materials. As an example, the average size of the CSD in nanocrystalline FeAl made by severe plastic deformation is determined in 3D. Assuming ellipsoidal CSD, it is deduced that the CSD have a width of 19 +/- 2 nm, a length of 18 +/- 1 nm, and a height of 10 +/- 1 nm. PMID- 22050967 TI - Biomonitoring of bisphenol A concentrations in maternal and umbilical cord blood in regard to birth outcomes and adipokine expression: a birth cohort study in Taiwan. AB - BACKGROUND: Bisphenol A (BPA) is a sealant and flux of plastic materials and has been determined to be an endocrine-disrupting chemical. Prenatal exposure to BPA can lead to substantial adverse effects on fetal growth and development. This study was conducted to assess BPA concentration in pregnant women and umbilical cord blood, and to investigate whether maternal BPA exposure affected fetal outcomes including lower birth weight (LBW), smaller size for gestational age (SGA), and high leptin (HLP) and low adiponectin (LAD) secretion. METHODS: We measured the BPA levels of maternal blood (n = 97) and umbilical cord blood (n = 97) with a high-performance liquid chromatography/UV detector. The protein secretion of leptin and adiponectin were separately determined using enzyme linked immunosorbent assay. A logistic regression was performed to estimate the effects of maternal exposure to BPA on LBW, SGA, and adverse action of adipokines in newborns. RESULTS: The geometric means of BPA concentration in maternal blood and fetal cord blood were 2.5 ng/ml and 0.5 ng/ml, respectively. Elevated risks of LBW (OR 2.42, 95% confidence interval (CI) 1.72-3.36), SGA (OR 2.01, 95% CI 1.39-3.01), and adverse action of leptin (OR 1.67, 95% CI 1.12-2.25) and adiponectin (OR 1.25, 95% CI 1.52-3.97) were observed in male neonates in the highest quartile of maternal BPA exposure. CONCLUSIONS: Elevated prenatal BPA exposure increased the risk of LBW, SGA, and adverse actions of adipokines in neonates, especially in male infants. These results provide further evidence that maternal exposure is correlated with adverse birth outcomes. PMID- 22050970 TI - Feeling more pain, yet showing less: the influence of social threat on pain. AB - The present study investigated the effects of social threat to physical integrity on reported pain and facial pain expression. Predictions of a cognitive appraisal model and a communicative perspective on pain expression were compared. Participants (N = 67) received 5 electric pain stimuli administered by a confederate. They were led to believe that 5 pain stimuli were the minimum, a fixed amount, or the maximum number of pain stimuli allowed, thereby varying the social threat posed by the confederate. Reported pain and facial pain expression were recorded during the delivery of pain stimuli. Increased perceived social threat led to an increase of reported pain, specifically for high pain catastrophizing participants, while it led to a reduction of facial pain expression. This is the first study to demonstrate that a social threat manipulation has opposite effects on reported pain and facial expression, suggesting differences in adaptive function for both forms of pain expression. PERSPECTIVE: This is the first demonstration showing an increase in verbal pain report and a decrease in nonverbal pain expression at the same time during social threat. This knowledge may contribute to improving pain assessment in different contexts. PMID- 22050972 TI - Gait status 17-26 years after selective dorsal rhizotomy. AB - The purpose of this study was to use three-dimensional gait analysis to describe the gait status of adults with spastic diplegia who underwent selective dorsal rhizotomy (SDR) in childhood. Outcome measures were the gait deviation index (GDI), non-dimensional temporal-distance parameters, and kinematics of the lower limbs. A total of 31 adults with spastic diplegia who had previously undergone SDR were eligible and participated in current study (SDR group). These participants had a median age of 26.8 years (range 21-44 years) with a mean time between surgery and assessment of 21.2+/-2.9 years (range 17-26 years). For comparison purposes, 43 typically developed adults also participated (CONTROL group), with a median age of 28.3 years (range 21-45 years). More than 17 years after SDR 58% of the SDR group showed improved GMFCS levels, while none of them deteriorated. The participants in the SDR group walked with a mild crouch gait, although there was a loading response, adequate swing-phase knee flexion, adequate swing-phase plantarflexion, reasonable speed and cadence. The gait status of the SDR group more than 17 years after SDR was similar to what has been reported in short-term follow-up studies, as well as our earlier 20 year follow up study that did not include 3D gait analysis. Appropriate orthopaedic intervention was required in 61% of the study cohort. Whether the types and numbers of orthopaedic interventions are positively affected by SDR remains an open question. Further studies examining this question are warranted. In addition, long-term follow-up studies focused on other interventions would also be of clinical relevance. PMID- 22050971 TI - Muscle paresis and passive stiffness: key determinants in limiting function in Hereditary and Sporadic Spastic Paraparesis. AB - BACKGROUND: People with Hereditary and Sporadic Spastic Parapresis (SP) walk with a stiff legged gait characterised by a lack of knee flexion. OBJECTIVE: We investigated the relationship between lower limb strength and stiffness and knee flexion during swing phase while walking in 20 people with SP and 18 matched controls. METHODS: Maximal isometric strength was measured using a dynamometer. Passive stiffness and spasticity was assessed during motor-driven slow (5 degrees /s) and fast (60 degrees /s) stretches at the ankle and knee while the subject was relaxed or preactivating the muscle. Walking was assessed using 3D motion analysis. RESULTS: Isometric muscle strength was decreased in people with SP with over a 50% reduction in strength being found in the ankle dorsiflexors. Passive stiffness, assessed during slow stretches, was 35% higher in the plantarflexors in people with SP (P<0.05). Faster stretches induced large stretch evoked muscle activity and over a 110% increase in stiffness at the ankle and knee in people with SP reflecting the presence of spasticity (P<0.05). However, stretch reflex size and stiffness was similar between the groups following identical stretches of the pre-activated muscle (P>0.05). Lower knee flexion during swing phase was associated with reduced knee flexion velocity at the end of stance phase which in turn was associated with reduced plantarflexor strength and increased passive stiffness in the knee extensors. CONCLUSIONS: The relative importance of muscle paresis and passive stiffness in limiting walking in SP suggests that these impairments should be the target of future therapies. PMID- 22050973 TI - The effect of an exercise ball on trunk muscle responses to rapid limb movement. AB - The use of exercise balls as an aid to facilitate improvements in posture in patients with trunk weakness is widely advocated. However, mechanisms underlying any effect on postural mechanisms have received little attention. This study compared the increases in trunk EMG activity in response to limb movement when seated on an exercise ball or on a chair in 16 healthy, moderately active subjects. At the sound of an auditory cue, the subjects carried out either hip flexion or arm flexion (unilateral or bilateral), as fast as possible, whilst sitting on an exercise ball or a standard chair. The amplitude of EMG activity was recorded from selected trunk muscles (erector spinae, external obliques, internal obliques and rectus abdominis) and either an upper limb muscle (deltoid) or a lower limb muscle (rectus femoris). There were minimal differences in amplitudes of EMG activity in any of the trunk muscles between the conditions (ball or chair) following the upper limb movements. These results suggest that there is no benefit in simple arm flexion movements whilst seated on the exercise ball in comparison to a chair. The onset and amplitude of the rectus abdominis (RA) and external obliques (EO) were significantly different between conditions in the hip flexion protocol. However, they do suggest significant benefit in decreasing RA and EO muscle activity onsets and increasing amplitude in the hip flexion condition. These results may have implications for rehabilitation of those with trunk muscle deficits such as stroke. PMID- 22050974 TI - Spring-like Ankle Foot Orthoses reduce the energy cost of walking by taking over ankle work. AB - In patients with central neurological disorders, gait is often limited by a reduced ability to push off with the ankle. To overcome this reduced ankle push off, energy-storing, spring-like carbon-composite Ankle Foot Orthoses (AFO) can be prescribed. It is expected that the energy returned by the AFO in late stance will support ankle push-off, and reduce the energy cost of walking. In 10 patients with multiple sclerosis and stroke the energy cost of walking, 3D kinematics, joint power, and joint work were measured during gait, with and without the AFO. The mechanical characteristics of the AFO were measured separately, and used to calculate the contribution of the AFO to the ankle kinetics. We found a significant decrease of 9.8% in energy cost of walking when walking with the AFO. With the AFO, the range of motion of the ankle was reduced by 12.3 degrees , and the net work around the ankle was reduced by 29%. The total net work in the affected leg remained unchanged. The AFO accounted for 60% of the positive ankle work, which reduced the total amount of work performed by the leg by 11.1% when walking with the AFO. The decrease in energy cost when walking with a spring-like energy-storing AFO in central neurological patients is not induced by an augmented net ankle push-off, but by the AFO partially taking over ankle work. PMID- 22050975 TI - Clinical utility of a complete diagnostic protocol for the ocular evaluation of free-living raptors. AB - OBJECTIVE: To describe a protocol for the examination of free-living raptors and report the ophthalmic examination findings of seven raptor species native to central Illinois, namely the barred owl, Cooper's hawk, eastern screech owl, great horned owl, American kestrel, red-tailed hawk, and turkey vulture and to determine if the findings relative to visual prognosis affected eligibility for future release. ANIMALS STUDIED: Seventy-nine free-living raptors. PROCEDURES: Under manual restraint, complete ophthalmic examination including slit-lamp biomicroscopy and indirect funduscopy, applanation tonometry, rebound tonometry, ocular morphometrics, B-mode ultrasound, and electroretinography (ERG) were performed on each bird. Histopathology of enucleated globes was performed after euthanasia or death in selected cases. RESULTS: The examination protocol was easily performed using manual restraint alone on all birds. Ocular lesions were detected in 48.1% of birds, with 47.3% affected unilaterally and 52.6% affected bilaterally. Ocular lesions were considered to be vision threatening in 29.0% of the unilaterally affected birds and 29.0% of the bilaterally affected birds. The most common case outcomes were discharge from hospital to rehabilitation facility (45.6%) followed by euthanasia (43.0%). The presence of an ocular lesion or a vision-threatening ocular lesion was not significantly associated with outcome. Reference ranges are reported for B-mode ultrasound, ocular morphometrics, and horizontal corneal diameter in all species. CONCLUSION: Complete ophthalmic examination can be supplemented by the use of ocular morphometrics, ultrasound, and ERG in the manually restrained raptor. These advanced diagnostic techniques may be useful in developing more objective criteria for evaluating eligibility for release following rehabilitation of free-living birds of prey. PMID- 22050976 TI - Can Seizure-Alert Dogs predict seizures? AB - An index observation where a dog was trained to alert to, as well as respond to, human tonic-clonic seizures led to further research and refinement of training techniques. This was followed by anecdotal reports of pet dogs spontaneously anticipating human epileptic seizures. An industry has since developed training Seizure-Alert Dogs (SADs) to give humans warnings of their seizures. In some cases this has been accompanied by a reduction in seizure frequency. SADs may be trained along with the person with epilepsy, responding specifically to that person's seizures, or may be trained separately. Recent sceptical reports of non epileptic seizures in some people with SADs have cast doubt on dogs' ability to anticipate true epileptic seizures. This may reflect selection criteria for training programmes as well as training methods used, but does not necessarily indicate that SADs might not be able to predict epileptic seizures. Whether the seizures are epileptic or non-epileptic, it is speculated that SADs probably alert to subtle pre-ictal human behaviour changes, but may also be sensitive to heart rate or olfactory cues. As yet, however, no rigorous data exist as to whether seizure prediction by SADS is better than chance, and what false positive and negative prediction rates might be. PMID- 22050977 TI - TMS studies of preictal cortical excitability change. AB - The transition between the interictal and ictal states may be characterised in terms of the dynamics of a complex system. Seizures may emerge because of a change in system parameters, but these parameters may be invisible to passive observation. Therefore, a number of investigators have developed methods to probe the system using stimulation; these probing stimuli may reveal important hidden parameters. Here we describe studies from two sets of investigators working independently, which have shown that motor responses to transcranial magnetic brain stimulation (TMS) differ between the interictal state remote from any seizure, and a period of hours immediately prior to a seizure. We place these studies in the context of the known physiology of motor responses to TMS and discuss how actively probing the state of brain excitability may open new windows on its dynamics. PMID- 22050979 TI - Long term outcomes in patients with preoperative generalized interictal epileptiform abnormalities following amygdalohippocampectomy. AB - We evaluated long term surgical outcomes in 21 patients with temporal lobe epilepsy and presurgical generalized interictal epileptiform discharges (IEDs). Following amygdalohippocampectomy, 12 patients (57.1%) were noted to have favorable outcomes (Engel classification of I-II). Favorable outcomes were significantly associated with a history of auras prior to seizure onset (p=0.021), the absence of generalized IEDs on postoperative EEG (p=0.024), and the presence of focal slowing on postoperative EEG (p=0.045). PMID- 22050978 TI - PCDH19 mutation in Japanese females with epilepsy. AB - PURPOSE: To determine the significance of PCDH19 mutations in Japanese females with epilepsy and to delineate their phenotypes. METHODS: PCDH19 sequencing analysis was performed in 116 females with various epilepsies, including 97 with Dravet syndrome (83.6%). They were referred for SCN1A analysis, and 52 carried SCN1A mutations. RESULTS: Seven heterozygous mutations in exon 1 were identified in 7 patients (6.0%): 2 frameshift, 2 nonsense, and 3 missense mutations. One patient was a monozygotic twin, and her sister with mild phenotype carried the same mutation. The main clinical features among these 8 patients included early seizure onset (<=25 months of age), seizure clusters (7/8), fever-associated seizures (7/8), single seizure type (6/8), and late deterioration of intellect (5/8). Seizure durations were generally up to a few minutes, and only one patient developed status epilepticus once. The main seizure types were generalized tonic clonic (4/8), tonic (3/8) and focal seizures, with (2/8) or without secondary generalization (3/8). Myoclonic, atonic and absence seizures were extremely rare. Two patients had Dravet syndrome (25%), and this proportion was significantly smaller than that in the total subjects (p<0.01). CONCLUSION: PCDH19 mutation is a relatively frequent cause of epilepsy in Japanese females. Dravet syndrome was rare in our cohort. PMID- 22050980 TI - Phenotypic differences between fast and slow methionine sulfoximine-inbred mice: seizures, anxiety, and glutamine synthetase. AB - Seizures induced by the convulsant methionine sulfoximine (MSO) resemble human "grand mal" epilepsy, and brain glutamine synthetase is inhibited. We recently selected two inbred lines of mice: sensitive to MSO (MSO-Fast) and resistant (MSO Slow). In the present study, the selection pressure was increased and consanguinity established. To gain insight into the mechanisms of epileptogenesis, we studied the behaviour of MSO-Fast and MSO-Slow mice based on their responses to various convulsants and anticonvulsants, and also the kinetics of glutamine synthetase. The results show that increasing the number of generations of sib-crossings resulted in an increase in the differences between MSO-Fast and MSO-Slow mice. The dose-response curve of MSO-dependent seizures demonstrated that the MSO-Slow mice were highly insensitive to MSO-dependent seizures compared with MSO-Fast inbred mice that were highly sensitivity. The MSO Slow were resistant to convulsions induced by various convulsants having different mechanisms of action, whereas those in the MSO-Fast line were more sensitive to kainic acid-induced seizures. These data, in addition to the effects of anticonvulsant, strongly suggest that glutamatergic pathways are most likely involved in MSO-dependent seizures, rather than GABAergic ones. This hypothesis is corroborated by the glutamine synthetase activity, which is more elevated in the MSO-Slow line. Behaviour tests showed that MSO-Slow were less anxious than MSO-Fast. Collectively, these results showed that glutamatergic pathways could be involved in the epileptogenic action of MSO, which may be related to the glutamate/glutamine cycle in the brain. PMID- 22050981 TI - Pre-ictal autonomic changes. AB - Autonomic measures frequently alter with seizure activity and with brain state and so theoretically, there could be pre-ictal changes in autonomic function. However, there are considerable confounders. First, the measurement of autonomic function is not straightforward; heart rate and measures derived form heart rate have been those that have used the most in assessing changes in autonomic function. Second, autonomic function can vary considerably over the 24h cycle and can change suddenly depending on internal and external stimuli (e.g. fear, pain) and so any measures of changes in autonomic function will lose specificity. Third, changes in autonomic function in response to seizures, depends upon the individual, seizure type and spread of the seizure and even then can vary from seizure to seizure in the same individual. The idea that there will be well defined, unique autonomic changes that occur in the pre-ictal period is very unlikely. These factors make it unlikely that autonomic function monitoring can be used successfully as a means of seizure prediction. However, in sleep, changes in autonomic function relate to changes in arousal state and since such states and the transition between such states may predict seizure occurrence in certain individuals, autonomic function could be a helpful determinant of seizure risk at certain stages of sleep. This hypothesis has, however, yet to be tested. PMID- 22050982 TI - Restricted cusp motion in right-left type of bicuspid aortic valves: a new risk marker for aortopathy. AB - OBJECTIVE: Bicuspid aortic valve disease is heterogeneous with respect to valve morphology and aortopathy risk. This study searched for early imaging predictors of aortopathy in patients with a bicuspid aortic valve with right-left coronary cusp fusion, the most common morphotype. METHODS: Time-resolved magnetic resonance imaging was performed in 36 subjects with nonstenotic, nonregurgitant bicuspid aortic valves and nondilated aortas and in 10 healthy controls with tricuspid aortic valves. Sinus dimensions (diameter, width, and height), ascending tract diameters, and wall strain were measured for each sinus/leaflet unit and corresponding ascending tract area to account for asymmetries. A novel parameter, "cusp opening angle," measured the degree of valve leaflet alignment to outflow axis in systole, quantifying cusp motility. Phase-contrast magnetic resonance imaging and computational fluid dynamic models assessed flow patterns. Aortic growth rate was estimated over a follow-up period ranging from 9 to 84 months. RESULTS: The expected restriction of bicuspid aortic valve opening (conjoint cusp opening angle, 62 degrees +/-5 degrees vs 76 degrees +/-3 degrees for nonfused leaflet and 75 degrees +/-3 degrees for tricuspid aortic valve cusps; P<.001) was confirmed, and the introduced parameter reproducibly quantified this phenomenon. Phase-contrast magnetic resonance imaging demonstrated systolic flow deflection toward the right, affecting the right anterolateral ascending wall. Computational models confirmed that restricted cusp motion alone is sufficient to cause the observed flow pattern. Ascending tract wall strain was not circumferentially homogeneous in bicuspid aortic valves. In multivariable analyses, the conjoint cusp opening angle independently predicted ascending aorta diameters and growth rate (P<.001). CONCLUSIONS: In the bicuspid aortic valve commonly defined as normofunctional by echocardiographic criteria, restricted systolic conjoint cusp motion causes flow deflection. The novel measurement introduced can quantify restricted cusp opening, possibly assuming prognostic importance. PMID- 22050983 TI - Beating heart surgery via right thoracotomy for reoperative mitral valve surgery: a safe and effective operative alternative. AB - OBJECTIVE: Right thoracotomy using ventricular fibrillation with cooling has been used for redo mitral valve surgery. This approach avoids the complications of redo sternotomy, such as injury to prior grafts and hemorrhage. As a further refinement, we have used a beating heart technique to further minimize complications while simplifying the operation. METHODS: We reviewed the outcomes of 450 patients who underwent redo mitral valve surgery via a right thoracotomy from 1996 to 2011 at the University of Michigan. Of these, 134 patients underwent redo mitral valve surgery with ventricular fibrillation, and 316 patients underwent beating heart surgery. Although operative eras were consecutive, patients' age, risk factors, New York Heart Association, and preoperative left ventricular ejection fraction were not significantly different. Core temperature on cardiopulmonary bypass for beating heart surgery was 32 degrees C versus 26 degrees C for ventricular fibrillation. RESULTS: Patients undergoing beating heart surgery had shorter periods of cardiopulmonary bypass: 81+/-9 minutes versus 113+/-36 minutes. Beating heart surgery required less blood products than ventricular fibrillation: 1.65+/-2 units versus 3.8+/-5 units packed red blood cells, 0.6+/-1.2 units versus 1.8+/-4 units fresh-frozen plasma, and 1.02+/-4 versus 7.5+/-17 platelet packs (all P<.01). Conversely, patients receiving ventricular fibrillation required longer postoperative ventilation: 34+/-101 hours versus 15.5+/-27 hours (P<.01). The 30-day mortality was similar for both (6.5% for beating heart and 7.4% for ventricular fibrillation), and postoperative length of stay was the same at 7 days. Stroke rate was 2.6% for patients undergoing beating heart surgery and 3% for patients receiving ventricular fibrillation. Significant operative complications were uncommon; there was no catastrophic hemorrhage, and only 2 patients receiving ventricular fibrillation and 2 patients undergoing beating heart surgery required reexploration. CONCLUSIONS: As reoperative cardiac surgery continues to increase, techniques that safely facilitate operation while improving outcome should be adopted. As an operative alternative, redo right thoracotomy mitral valve surgery on the beating heart is associated with shorter bypass time, less transfusion requirements, shorter postoperative ventilation, and lower mortality. This safe and effective approach should be considered for this complex operation. PMID- 22050985 TI - Pulmonary artery sling: current results with cardiopulmonary bypass. AB - OBJECTIVE: We have used cardiopulmonary bypass with left pulmonary artery reimplantation for pulmonary artery sling repair since 1985. This review presents our current results with this technique, emphasizing the importance of diagnosis and treatment of frequently associated tracheal stenosis. METHODS: Since 1985, 34 patients have undergone pulmonary artery sling repair using a median sternotomy and cardiopulmonary bypass. Age ranged from 9 days to 43 years (mean 2.1 +/- 7.5 years, median 0.2 years). Twenty-seven patients (79%) had tracheal stenosis secondary to complete cartilage tracheal rings. All patients had preoperative airway imaging with rigid bronchoscopy, and since 2000 all patients have had computed tomography imaging of the chest with 3-dimensional reconstruction (n = 14). Tracheal repair has included pericardial patch tracheoplasty (n = 7), tracheal autograft (n = 10), tracheal resection (n = 4), and slide tracheoplasty (n = 5). All patients had an echocardiogram, and cardiac lesions repaired simultaneously included atrial septal defect (4), tetralogy of Fallot (2), and ventricular septal defect (1). One patient had a severely hypoplastic right lung, and 3 patients had an absent right lung. In these patients, the left pulmonary artery was translocated anterior to the trachea. In all other patients, the left pulmonary artery was reimplanted into the main pulmonary artery. RESULTS: There have been no early deaths or complications related to the use of cardiopulmonary bypass. Median hospital stay was 24 days. There have been 4 late deaths. Two late deaths were the result of complications of tracheal surgery (1 pericardial patch [6 months postoperatively] and 1 autograft [1.7 years postoperatively]). One child died of biliary atresia (0.2 years postoperatively), and 1 child died of pneumonia (5.8 years postoperatively). All recent tracheal stenosis repairs have been with slide tracheoplasty. All left pulmonary arteries are patent with a mean percent flow by perfusion scan of 41% +/- 13%. Older patients (n = 2) have noted a significant improvement in exercise tolerance. CONCLUSIONS: Pulmonary artery sling is best repaired with median sternotomy, cardiopulmonary bypass, and left pulmonary artery reimplantation. This resulted in uniformly patent left pulmonary arteries in all patients. Preoperative computed tomography imaging, echocardiography, and bronchoscopy are essential for precise operative planning. The frequently associated tracheal stenosis is best repaired with slide tracheoplasty. PMID- 22050986 TI - Coarctectomy combined with an interdigitating arch reconstruction results in a lower incidence of recurrent arch obstruction after the Norwood procedure than coarctectomy alone. AB - OBJECTIVE: Recurrent aortic arch obstruction after the Norwood procedure continues to be a source of morbidity. We sought to determine if a modified interdigitating technique for aortic arch reconstruction during the Norwood procedure decreased recurrent arch obstruction. METHODS: A total of 142 consecutive infants undergoing the Norwood procedure were divided into groups according to surgical technique: Group 1 (n = 79, January 1999 to May 2003) underwent arch reconstruction with complete coarctectomy followed by anastomosis of the descending aorta to the transverse arch. Group 2 (n = 63, June 2003 to September 2006) underwent complete coarctectomy plus a modified interdigitating technique. Catheterization before stage 2 palliation was reviewed for hemodynamics and angiographic arch dimensions, and a coarctation index was calculated. RESULTS: Reintervention for recurrent coarctation occurred in 28% (22/79) of group 1 patients compared with 2% (1/63) of group 2 patients (P = .001). Aortic pressures, gradients, dimensions, and coarctation index were consistently more favorable for group 2. CONCLUSIONS: Coarctectomy plus an interdigitating arch anastomosis was superior to coarctectomy alone and resulted in a dramatically decreased incidence of recurrent arch obstruction. PMID- 22050987 TI - Preoperative proteinuria predicts acute kidney injury in patients undergoing cardiac surgery. AB - OBJECTIVE: The study objective was to examine the utility of using proteinuria in preoperative risk stratification for acute kidney injury. Acute kidney injury is a common and important complication for patients undergoing cardiac surgery. Proteinuria, which reflects structural damage to the glomeruli or renal tubules, may aid the prediction of acute kidney injury. METHODS: The urine albumin to creatinine ratio and dipstick proteinuria concentration were prospectively measured in 1159 patients undergoing cardiac surgery. The cohort was organized into 4 clinical risk categories based on the preoperative urine albumin to creatinine ratio: 10 mg/g or less (<= 1.1 mg/mmol), 11 to 29 mg/g (1.2-3.3 mg/mmol), 30 to 299 mg/g (3.4-33.8 mg/mmol), and 300 mg/g or greater (>= 33.9 mg/mmol). The primary outcome was postoperative acute kidney injury, defined by the Acute Kidney Injury Network stage I criterion (serum creatinine increase >= 50% or >= 0.3 mg/dL; 26.5 MUmol/L). RESULTS: An increase in the incidence of acute kidney injury was noted across the urine albumin to creatinine ratio categories. Adding the urine albumin to creatinine ratio to the clinical model to predict acute kidney injury improved the area under the curve from 0.67 to 0.70 (P < .001), and the continuous net reclassification improvement was 29% (P < .001). The urine albumin to creatinine ratio was also independently associated with the risk of in-hospital dialysis and intensive care unit and hospital lengths of stay. Surgery status and preoperative glomerular filtration rate were effect modifiers; the association was stronger among those undergoing elective surgery and those with an estimated glomerular filtration rate of 45 mL/min/1.73 m(2) or greater. CONCLUSIONS: Preoperative proteinuria provides graded stratification risk for acute kidney injury and is an independent predictor of other outcomes in patients undergoing cardiac surgery. PMID- 22050988 TI - Training residents in off-pump coronary artery bypass surgery: a 14-year experience. AB - OBJECTIVE: Off-pump coronary artery bypass grafting (OPCAB) is an established procedure in many cardiothoracic centers. For it to be widely applicable, however, teaching methods must be developed for surgical trainees. Early clinical outcomes and long-term survival of patients who underwent OPCAB at our institution by trainees supervised and unsupervised were compared with those of patients whose procedures were performed by senior surgeons. To evaluate evolution of training, outcomes were analyzed according to 3 different periods (1996-1999, 2000-2004, 2005-2009) and trainee seniority level. METHODS: This was a retrospective, observational cohort study of prospectively collected data from 5566 consecutive patients who underwent isolated OPCAB performed by trainees (1589, 28.6%; 1111 supervised, 478 unsupervised) and by senior surgeons (3977, 71.4%). RESULTS: Patients of senior surgeons were more likely to have left ventricular dysfunction (P = .001), peripheral vascular disease (P = .05), more extensive coronary artery disease (P = .001), and higher EuroSCOREs than patients of trainees. In addition, trainees were less likely to have performed urgent operations (P = .02) or reoperations (P = .03) but more likely to have operated on patients with previous percutaneous coronary intervention (P = .006). Early clinical outcomes and long-term survival were similar between groups and not related to trainee seniority, level of supervision by senior surgeon, or period during which training took place. CONCLUSIONS: OPCAB is a safe and reproducible surgical technique that can be taught successfully to cardiothoracic trainees. Clinical outcomes are unrelated to level of supervision or seniority of trainees. PMID- 22050989 TI - Pseudoprolapse of the anterior leaflet in chronic ischemic mitral regurgitation: identification and repair. AB - OBJECTIVE: Recurrence rates as high as 30% have been observed 6 months after treatment of chronic ischemic mitral regurgitation (CIMR) with isolated annuloplasty. We postulated that the high early recurrence rates resulted from the presence of untreated pseudoprolapse of the anterior leaflet. METHODS: We conducted a retrospective study of all mitral valve repairs for CIMR performed by a single surgeon (S.W.H.) from 1995 to 2011. After annuloplasty, Gore-Tex neochordae were added if the high-pressure saline test indicated the presence of pseudoprolapse of the anterior leaflet. RESULTS: A total of 47 patients underwent mitral valve repair for CIMR. Of the 47 patients, 24 (51%) were found to have pseudoprolapse requiring the addition of neochordae. For all patients, the average age was 65.1 years, and 65.2% were men. Fourteen (30%) had had a preoperative intra-aortic balloon pump placed by cardiologists. Fourteen (30%) had severe pulmonary hypertension. Concomitant coronary artery bypass grafting was performed in 40 patients, with an average of 2.2 grafts; 7 had previously undergone coronary artery bypass grafting. Mitral Carpentier-Edwards physio annuloplasty rings were used in all patients with a mean size of 29 mm. One patient died postoperatively. Follow-up data were available for all 47 patients at an average of 4.9 years. The 5-year survival rate was 82.5%. The mean pre- and postoperative New York Heart Association class, ejection fraction, and mitral regurgitation grade were 3 and 1.52 (P < .0001), 34% and 41% (P = .0006), and 3.51 and 1.08 (P < .0001), respectively. Two patients developed greater than moderate mitral regurgitation. CONCLUSIONS: Effective repair of CIMR should include surgical techniques to correct pseudoprolapse of the anterior leaflet, when present. The selective addition of Gore-Tex neochordae to an undersized annuloplasty nearly eliminates recurrent regurgitation after mitral valve repair for CIMR. PMID- 22050990 TI - Papillary muscle relocation in conjunction with valve annuloplasty improve repair results in severe ischemic mitral regurgitation. AB - OBJECTIVE: The incidence of recurrent mitral regurgitation (MR) after restrictive annuloplasty (RA) was 5% to 20% in several reports. There are many opinions in favor of adding subvalvular procedures to RA to reduce the tenting forces and improve the repair results. METHODS: From March 2003 to May 2010, 55 patients with severe ischemic MR who had undergone papillary muscle (PPM) relocation in conjunction with mitral annuloplasty in our institutions were enrolled. The patients were matched 1:1 with those who underwent isolated RA using the propensity score. The mean left ventricular ejection fraction was 42% +/- 6%. The mean tenting area and coaptation depth was 3.2 +/- 0.6 cm(2) and 1.3 +/- 0.2 cm, respectively. The study endpoints were early mortality and clinical and echocardiographic outcomes, freedom from cardiac-related deaths, and cardiac related events. RESULTS: In-hospital death occurred in 5 patients (4.5%), without a statistically significant difference between the 2 groups (P = .72). The 5-year freedom from cardiac-related deaths and cardiac-related events in the PPM relocation group versus the RA group was 90.9% +/- 1.8% versus 89% +/- 1.6% (P = .82) and 83% +/- 2.1% versus 65.4% +/- 1.2% (P < .001), respectively. Recurrent MR equal to or greater than moderate occurred in 2 (3.7%) and 6 (11.5%) patients in the PPM relocation group and RA group (P = .01), respectively. Moreover, we found statistically significant differences for the postoperative mean tenting area and coaptation depth in both groups (P < .001). CONCLUSIONS: PPM relocation in conjunction to mitral annuloplasty is an easy and safe method and can be performed without an increase in-hospital mortality. This technique reduced the tenting area and coaptation depth compared with isolated RA, leading to improvement in the incidence of recurrent MR. The PPM group of patients experienced fewer cardiac-related events. PMID- 22050991 TI - Importance of anterior leaflet tethering in predicting recurrence of ischemic mitral regurgitation after restrictive annuloplasty. AB - OBJECTIVE: We investigated the relationship between anterior mitral leaflet (AML) tethering and recurrent ischemic mitral regurgitation (MR) after restrictive annuloplasty. We also explored whether the effect of AML tethering was secondary to modifications in left ventricular size and geometry. METHODS: The study population consisted of 435 consecutive patients with chronic ischemic MR who survived combined coronary artery bypass grafting and undersized mitral ring annuloplasty performed at 3 institutions (University Hospital, Maastricht, The Netherlands; Careggi Hospital, Florence, Italy; and Civic Hospital, Brescia, Italy) from 2001 to 2008. The median follow-up was 44.7 months (interquartile range 25.9-66.4). The patients were divided by the baseline measurements into quintiles of AML tethering angle alpha' as follows: group 1, normal/slight AML tethering; group 2, mild AML tethering; group 3, moderate AML tethering; group 4, moderate-to-severe AML tethering; and group 5, severe AML tethering. RESULTS: Recurrence of MR was significantly greater in patients with moderate-to-severe (28.3%) and severe (39.4%) AML tethering (P < .001). A strong correlation was found between alpha' (r = 0.83, P < .001) and recurrent MR but a weak correlation with the posterior mitral angle beta' (r = 0.12, P = .05). On logistic regression analysis corrected for other echocardiographic risk factors, moderate-severe AML tethering or worse (adjusted odds ratio, 3.6; 95% confidence interval, 3.0-4.1; P < .001) was a strong predictor of MR recurrence. Compared with patients with beta' of 45 or greater, those with severe and moderate-severe AML tethering had more than 3.7 and 1.7 times greater odds of MR recurrence, respectively. No significant interactions were found between alpha' and the indexes of left ventricular function and geometry. CONCLUSIONS: Preoperative moderate-severe AML tethering or worse was strongly associated with MR recurrence. Thus, assessment of leaflet tethering should be incorporated into clinical risk assessment and prediction models. PMID- 22050992 TI - Stimulation of Ca2+-sensing receptor inhibits the basolateral 50-pS K channels in the thick ascending limb of rat kidney. AB - We used the patch-clamp technique to study the effect of changing the external Ca2+ on the basolateral 50-pS K channel in the thick ascending limb (TAL) of rat kidney. Increasing the external Ca2+ concentration from 1 mM to 2 or 3 mM inhibited the basolateral 50-pS K channels while decreasing external Ca2+ to 10 MUM ?increased the 50-pS K channel activity. The effect of the external Ca2+ on the 50-pS K channels was observed only in cell-attached patches but not in excised patches. Moreover, the inhibitory effect of increasing external Ca2+ on the 50-pS K channels was absent in the presence of NPS2390, an antagonist of Ca2+ sensing receptor (CaSR), suggesting that the inhibitory effect of the external Ca2+ was the result of stimulation of the CaSR. Application of the membrane permeable cAMP analog increased the 50-pS K channel activity but did not block the effect of raising the external Ca2+ on the K channels. Neither inhibition of phospholipase A2 (PLA2) nor suppression of cytochrome P450-omega-hydroxylation dependent metabolism of arachidonic acid was able to abolish the effect of raising the external Ca2+ on the 50-pS K channels. In contrast, inhibition of phospholipase C (PLC) or blocking protein kinase C (PKC) completely abolished the inhibition of the basolateral 50-pS K channels induced by raising the external Ca2+. We conclude that the external Ca2+ concentration plays an important role in the regulation of the basolateral K channel activity in the TAL and that the effect of the external Ca2+ is mediated by the CaSR which stimulates PLC-PKC pathways. The regulation of the basolateral K channels by the CaSR may be the mechanism by which extracellular Ca2+ level modulates the reabsorption of divalent cations. PMID- 22050994 TI - Network analysis of microRNAs and their regulation in human ovarian cancer. AB - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development. RESULTS: We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with ab initio transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network's behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis. CONCLUSIONS: We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance our understanding of the molecular mechanisms underlying human cancer development and OC in particular. PMID- 22050995 TI - A computational index derived from whole-genome copy number analysis is a novel tool for prognosis in early stage lung squamous cell carcinoma. AB - Squamous cell carcinoma of the lung is remarkable for the extent to which the same chromosomal abnormalities are detected in individual tumours. We have used next generation sequencing at low coverage to produce high resolution copy number karyograms of a series of 89 non-small cell lung tumours specifically of the squamous cell subtype. Because this methodology is able to create karyograms from formalin-fixed paraffin-embedded material, we were able to use archival stored samples for which survival data were available and correlate frequently occurring copy number changes with disease outcome. No single region of genomic change showed significant correlation with survival. However, adopting a whole-genome approach, we devised an algorithm that relates to total genomic damage, specifically the relative ratios of copy number states across the genome. This algorithm generated a novel index, which is an independent prognostic indicator in early stage squamous cell carcinoma of the lung. PMID- 22050996 TI - New triterpenoid saponins from Patrinia scabiosaefolia. AB - Phytochemical investigation of the methanol extract from the whole plants of Patrinia scabiosaefolia Fisch. resulted in the isolation of four new triterpenoid saponins (1-4) along with six known compounds (5-10). On the basis of spectroscopic and chemical methods, the structures of the new compounds were established as 3-O-beta-D-xylopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->2) beta-D-xylopyranosyl-12beta,30-dihydroxy-olean-28,13beta-olide (1), 3-O-alpha-L rhamnopyranosyl-(1->2)-beta-D-xylopyranosyl-12beta,30-dihydroxy-olean-28,13beta olide (2), 3-O-beta-D-xylopyranosyl-(1->2)-beta-D-glucopyranosyl-12beta, 30 dihydroxy-olean-28,13beta-olide (3), and 3-O-beta-D-glucopyranosyl-(1->4)-beta-D xylopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->2)-beta-D-xylopyranosyl oleanolic acid 28-O-beta-D-glucopyranoside (4), respectively. Compounds 1-3 possess a novel 12beta,30-dihydroxy-olean-28,13beta-lactone aglycone and a 12beta hydroxy substituent that is rarely found in this kind of triterpenoid saponin. PMID- 22050997 TI - Glycosylation studies on conformationally restricted 3,5-O-(di-tert butylsilylene)-D-galactofuranosyl trichloroacetimidate donors for 1,2-cis alpha-D galactofuranosylation. AB - Conformationally restricted 3,5-O-di-tert-butylsilylene-D-galactofuranosyl trichloroacetimidate donors were synthesized from allyl alpha-D-galactofuranoside for the construction of 1,2-cis alpha-D-galactofuranosyl linkages. Glycosylation reactions were performed with several acceptors, including D-galactono-1,4 lactone, D-rhamnopyranosyl, and D-mannopyranosyl derivatives. The influence of the temperature and the reaction solvents was evaluated, as well as the 6-O substitution pattern of the donor. The higher alpha-selectivities were obtained at -78 degrees C in diethyl ether as solvent. 6-O-Acetyl substitution on constrained donor increased the alpha-selectivity compared to the 6-O-benzyl substitution. Almost no selectivities were observed in the non-participating solvent CH(2)Cl(2). In contrast, ethereal solvents enhanced the alpha-selectivity suggesting a participating effect in the reaction intermediate. PMID- 22050998 TI - Microanatomy of the anterior uveoscleral outflow pathway in normal and primary open-angle glaucomatous dogs. AB - OBJECTIVE: To compare the morphology of the uveoscleral (US) outflow pathway in normal and glaucomatous canines. ANIMALS STUDIED: 10 normal beagles, 10 beagles with inherited primary open-angle glaucoma, 4 cocker spaniels with spontaneous glaucoma. PROCEDURES: Formalin-preserved globes were sectioned tangentially and sagittally and treated with H&E, Masson's trichrome, or elastin stains or analyzed by immunohistochemistry to visualize smooth muscle actin. Tissues associated with the US pathway were observed and compared using light microscopy. RESULTS: Tangentially oriented sections clearly revealed spaces for the transport of aqueous humor at the junction of the posterior iridocorneal angle (ICA) and anterior ciliary body musculature (CBM). Within the external anterior-most of the US pathway, the supraciliary space, distinct connective tissue cords and smooth muscle pegs fastened the ciliary body to the adjacent sclera. Compared to normal controls, glaucomatous eyes developed a robust scleral elastic sheath at the junction between the posterior ICA and the anterior CBM. In advanced glaucomatous beagles and cocker spaniels, a large amount of melanophores were seen in the US pathway and surrounding vasculature. Within the C8M of glaucomatous specimens, the smooth muscle bundles appeared fewer and separated by elastic-rich ECM. Structures of the US pathway changed little with age. CONCLUSIONS: The anterior portion of the canine US pathway is well defined and appears to be altered little with age. However with glaucoma, changes of the US pathway were associated with its the elastic components, as well as the accumulation of melanophores. Collectively, these changes may have an effect on US outflow and, subsequently, aqueous humor dynamics. PMID- 22050999 TI - Long-term prognosis of symptomatic isolated middle cerebral artery disease in Korean stroke patients. AB - BACKGROUND: This study aimed to investigate the long-term mortality and recurrence rate of stroke in first-time stroke patients with symptomatic isolated middle cerebral artery disease (MCAD) under medical management. METHODS: We identified 141 first ever stroke patients (mean age, 64.4 +/- 12.5 years; 53% male) with symptomatic isolated MCAD. MCAD was defined as significant stenosis of more than 50% or occlusion of the MCA as revealed by MR angiography. The median follow-up was 27.7 months. We determined a cumulative rate of stroke recurrence and mortality by Kaplan-Meier survival analyses and sought predictors using the Cox proportional hazard model. RESULTS: The cumulative composite outcome rate (stroke recurrence or any-cause death) was 14%, 19%, 22%, and 28% at years 1, 2, 3, and 5, respectively. The annual recurrence rate of stroke was 4.1%. The presence of diabetes mellitus was the only significant independent predictor of stroke recurrence or any cause of death in multivariate analyses of Cox proportional hazard model adjusted for any plausible potential confounding factors. CONCLUSIONS: We estimated the long-term prognosis of stroke patients with isolated symptomatic MCAD under current medical management in Korea. Diabetes mellitus was found to be a significant predictor for stroke recurrence and mortality. PMID- 22051000 TI - Gender identity issues in youth: opportunities, terminologies, histories, and advancements. AB - An expanding number of mental health professionals evaluate, advocate for, treat, and refer gender variant children and transgender youth.Official recognition of these persons and their needs as well as support for improvement and change come from several different national surveys and professional policy and accreditation organizations. Being informed about these and other available resources can help with patient advocacy. The author provides a reading list for youth and families, definitions of terms, a history of youth gender variance, history and policies of professional organizations, and recent reports and initiatives. An appendix with a patient's first-hand story is included. PMID- 22051001 TI - Thoughts on the nature of identity: disorders of sex development and gender identity. AB - Children with disorders of sex development have similarities to, but also marked contrasts with, children with normal anatomy but who have gender dysphoria. Understanding gender identity development in children with sex disorders will probably help us understand typical gender identity development more than in understanding gender development in children with gender identity disorder. PMID- 22051002 TI - Gender monitoring and gender reassignment of children and adolescents with a somatic disorder of sex development. AB - Individuals born with a somatic disorder of sex development (DSD) have high rates of gender-atypical behavior, gender uncertainty, gender dysphoria, and patient initiated gender change in childhood, adolescence,and adulthood. This article addresses the issues a mental health services provider has to consider in evaluating and assisting such patients and provides examples of assessment-method batteries. To date, the World Professional Association for Transgender Health's Standards of Care, 6th version, for non-DSD patients with gender dysphoria, may be cautiously used for guidance, taking into account the considerable differences in presentation and medical context between gender dysphoric patients with and without a DSD. PMID- 22051003 TI - Development of AACAP practice parameters for gender nonconformity and gender discordance in children and adolescents. AB - The American Academy of Child and Adolescent Psychiatry (AACAP) is preparing a publication, Practice Parameter on Gay, Lesbian or Bisexual Sexual Orientation, Gender-Nonconformity, and Gender Discordance in Children and Adolescents. This article discusses the development of the part of the parameter related to gender nonconformity and gender discordance and describes the practice parameter preparation process,rationale, key scientific evidence, and methodology. Also discussed are terminology considerations, related clinical issues and practice skills, and overall organization of information including influences on gender development, gender role behavior, gender nonconformity and gender discordance, and their relationship to the development of sexual orientation. PMID- 22051004 TI - Assessment of gender variance in children. AB - This article focuses on the assessment of children who display gender-atypical behavior and, perhaps, identity. The aim is to provide an overview of assessment techniques that can be used clinically with children who show this behavioral pattern and that complement the routine use of DSM-IV criteria for the diagnosis of gender identity disorder in clinical practice. It will also provide an overview of some common approaches to the assessment of other types of behavioral and socioemotional issues that may require clinical attention in these youngsters. PMID- 22051005 TI - Female-to-male transgender adolescents. AB - This article focuses on considerations for natal females who present in the adolescent years with concerns related to their gender. They maybe individuals previously evaluated in their childhood years who have persisted with gender variance or gender identity disorder (GID) in DSM-IV, or they may be presenting for the first time in their adolescent years. The article discusses how to assess adolescents who come for evaluation and what treatments and other resources are available for them and their families. Where there seem to be differences between boys and girls with gender identity issues, they will be noted. PMID- 22051006 TI - Treatment of adolescents with gender dysphoria in the Netherlands. AB - In the Netherlands, gender dysphoric adolescents may be eligible for puberty suppression at age 12, subsequent cross-sex hormone treatment at age 16, and gender reassignment surgery at age 18. Initially, a thorough assessment is made of the gender dysphoria and vulnerabilities in functioning or circumstances. Psychological interventions and/or gender reassignment may be offered. Psychological interventions are offered if the adolescent needs to explore gender identity and treatment wishes, suffers from coexisting problems, or needs support and counseling during gender reassignment. Although more studies are necessary, this approach seems to contribute significantly to the well-being of gender dysphoric adolescents. PMID- 22051007 TI - The development of a gender identity psychosocial clinic: treatment issues, logistical considerations, interdisciplinary cooperation, and future initiatives. AB - Few interdisciplinary treatment programs that tend to the needs of youth with gender nonconforming behaviors, expressions, and identities exist in academic medical centers with formal residency training programs. Despite this, the literature provides evidence that these youth have higher rates of poor psychosocial adjustment and suicide attempts. This article explores the logistical considerations involved in developing a specialized interdisciplinary service to these gender minority youth in accordance with the existing treatment guidelines.Demographic data will be presented and treatment issues will be explored. The impact that a specialized interdisciplinary treatment program has on clinical expansion, research development, education and training, and community outreach initiatives is discussed. PMID- 22051008 TI - Guidelines for pubertal suspension and gender reassignment for transgender adolescents. AB - Pubertal suppression at Tanner stage 2 should be considered in adolescents with persistent gender identity disorder (GID). Issues related to achievement of adult height, timing of initiating sex steroid treatment, future fertility options, preventing uterine bleeding, and required modifications of genital surgery remain concerns. Concerns have been raised about altering neuropsychological development during cessation of puberty and reinitiation of puberty by the sex steroid opposite those determined by genetic sex. Collaborative assessment and treatment of dysphoric adolescents with persistent GID resolves these concerns and deepens our understanding of gender development. PMID- 22051009 TI - A therapeutic group for parents of transgender adolescents. AB - Therapy for transgender, transsexual, and gender variant persons has traditionally assisted individuals in the process of adjusting to their newly adopted gender role. Increasingly, younger gender variant patients,teens and preteens, present to the clinical consultation raising the need to develop therapeutic interventions that better address the psychosocial needs of minors. The Gender and Sexuality Development Program at Children's National Medical Center (CNMC) in Washington,DC (http://www.childrensnational.org/gendervariance), provides outpatient psychosocial evaluations and therapeutic services for children,adolescents, and their families. PMID- 22051010 TI - Snakes and snails and mermaid tails: raising a gender-variant son. AB - This article is a first-person account of a father's journey to lovingly accept his young gender-variant son, who began to show traits and preferences more common to girls almost from birth. The dad's efforts to discover constructive parenting strategies for raising his boy are also detailed. Experiences described begin with guilt and awareness of his own difficulty in coming to terms with his son's behavior, progress toward seeking and finding support and guidance, and eventually learning to embrace his son as he is, perhaps with questions about his own liberality and apprehensions about his boy's future. PMID- 22051011 TI - Raising a gender non-conforming child. AB - This article overviews the challenges parents face raising gender non-conforming children. The author is the mother of a fifteen year old gender non-conforming (GNC) child and co-founder of Stepping Stones Support Group which organizes support programs for families of GNC. The article discusses social challenges, educational challenges and internal conflicts the author has experienced while raising her child. The author also discusses the process of founding Stepping Stones and the importance having support has played in her and her child's life. PMID- 22051012 TI - Considerations for affirming gender nonconforming boys and their families: new approaches, new challenges. AB - The media and the public's reaction have created the impression that gender variant behaviors of many children are indicative of later transsexual identities. This has suggested to some parents that the best way to manage their sons' gender variance and perhaps gender dysphoria is to allow them to dress as girls in increasingly more situations. For some this becomes a transition to living full-time as a girl. However, the author believes that most of these boys would be better served by helping them develop an awareness of the many ways of being a boy, stigma-reducing social strategies, and facilitating a positive gay identity. PMID- 22051013 TI - Improving medical education about gender-variant youth and transgender adolescents. AB - Gender minority children and adolescents present to a wide variety of health professionals for gender-related care and other care. However,few professionals may be prepared to meet their needs. Unprepared clinicians risk developing insufficient therapeutic rapport, missing salient information, and inadvertently contributing to risk. In this article the authors outline ways to address these gaps at all training levels to meet the needs of gender minority children and adolescents. They provide practical resources for colleagues interested in expanding education opportunities in their own community. In the end, competency in gender minority health should improve access to care for these youths. PMID- 22051014 TI - Finding clarity through the confusion. PMID- 22051015 TI - Gender-variant children and transgender adolescents. PMID- 22051017 TI - Angular smoothing and radial regularization of ODF fields: application on deterministic crossing fiber tractography. AB - The advent of high angular resolution diffusion imaging (HARDI) has opened up new perspectives for the delineation of crossing and branching fiber pathways. However, image acquisition under clinical conditions with limited measurement time faces the problem of poor spatial and angular resolution and the technique's high susceptibility to noise. In this paper we present a straightforward spatial filter for ODF fields that uses the data-inherent structural information around a voxel as part of a directionally selective method for angular smoothing and radial regularization (ASRR). Especially in regions where fibers cross (multimodal voxels), the method allows us to reduce noise, improve the accuracy of ODF diffusion peaks, and strengthen signals of non-dominant fibers. Moreover, we propose a dynamic scheme in which regularization is applied only to ODFs classified as multimodal. The approach is quantitatively evaluated on synthetic datasets of various configurations. With an in vivo dataset of a human subject, measured under clinical imaging conditions, we demonstrate the method's ability to improve tractography of non-dominant transcallosal fiber pathways and the long fibers of the superior longitudinal fasciculus. PMID- 22051018 TI - Conformational changes of the betaine transporter BetP from Corynebacterium glutamicum studied by pulse EPR spectroscopy. AB - The betaine transporter BetP from Corynebacterium glutamicum is activated by hyperosmotic stress critically depending on the presence and integrity of its sensory C-terminal domain. The conformational properties of the trimeric BetP reconstituted in liposomes in the inactive state and during osmotic activation were investigated by site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy. Comparison of intra- and intermolecular inter spin distance distributions obtained by double electron-electron resonance (DEER) EPR with the crystal structure of BetP by means of a rotamer library analysis suggest a rotation of BetP protomers within the trimer by about 15 degrees as compared to the X-ray structure. Furthermore, we observed conformational changes upon activation of BetP, which are reflected in changes of the distances between positions 545 and 589 of different protomers in the trimer. Introduction of proline at positions 550 and 572, both leading to BetP variants with a permanent (low level) transport activity, caused changes of the DEER data similar to those observed for the activated and inactivated state, respectively. This indicates that not only displacements of the C-terminal domain in general but also concomitant interactions of its primary structure with surrounding protein domains and/or lipids are crucial for the activity regulation of BetP. PMID- 22051020 TI - Elastic, electrostatic and electrokinetic forces influencing membrane curvature. AB - Many cellular and intracellular processes critically depend on membrane shape, but the shape generating mechanisms are still to be fully understood. In this study we evaluate how electrostatic/electrokinetic forces contribute to membrane curvature. Membrane bilayer had finite thickness and was either elastically anisotropic or anisotropic overall, but isotropic per sections (heads and tails). The physics of the situation was evaluated using a coupled system of elastic and electrostatic/electrokinetic (Poisson-Nernst-Planck) equations. The fixed charges present only on the upper membrane surface lead to the accumulation of counter ions and depletion of co-ions that decay spatially very rapidly (Debye length<1nm), as does the potential and electric field. Spatially uneven electric field and the permittivity mismatch also induce charges at the membrane-solution interface, which are not fixed but influence the electrostatics nevertheless. Membrane bends due to - Coulomb force (caused by fixed membrane charges in the electric field) and the dielectric force (due to the non-uniform electric field and the permittivity mismatch between the membrane and the solution). Both act as membrane surface forces, and both depend supra-linearly on the fixed charge density. Regardless of sign of the fixed charges, the membrane bends toward the charged (upper) surface owing to the action of the Coulomb force, but this is opposed by the smaller dielectric force. The spontaneous membrane curvature becomes very pronounced at high fixed charge densities, leading to very small spontaneous radii (<50nm). In conclusion the electrostatic/electrokinetic forces contribute significantly to the membrane curvature. PMID- 22051019 TI - Voltage-dependant anion channels: novel insights into isoform function through genetic models. AB - Voltage-dependant Anion Channels, also known as mitochondrial porins, are pore forming proteins located in the mitochondrial outer membrane (MOM) that, in addition to forming complexes with other proteins that localize to the MOM, also function as the main conduit for transporting metabolites between the cytoplasm and mitochondria. VDACs are encoded by a multi-member gene family, and the number of isoforms and specific functions of VDACs varies between species. Translating the well-described in vitro characteristics of the VDAC isoforms into in vivo functions has been a challenge, with the generation of animal models of VDAC deficiency providing much of the available information about isoform-specific roles in biology. Here, we review the approaches used to create these insect and mammalian animal models, and the conclusions reached by studying the consequences of loss of function mutations on the genetic, physiologic, and biochemical properties of the resulting models. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism. PMID- 22051021 TI - Kinetics of demetallation of a zinc-salophen complex into liposomes. AB - A Zn-salophen complex has been incorporated into POPC large unilamellar liposomes (LUV) obtained in phosphate buffer at pH 7.4. Fluorescence optical microscopy and anisotropy measurements show that the complex is located at the liposomal surface, close to the polar headgroups. The interaction of the POPC phosphate group with Zn(2+) slowly leads to demetallation of the complex. The process follows first order kinetics and rate constants have been measured fluorimetrically in pure water and in buffered aqueous solution. The coordination of the phosphate group of monomeric POPC with salophen zinc also occurs in chloroform as detected by ESI-MS measurements. The effect of the Zn-salophen complex on the stability of POPC LUV has been evaluated at 25 degrees C by measuring the rate of release of entrapped 5(6)-carboxyfluorescein (CF) in the presence and in the absence of Triton X-100 as the perturbing agent. It turns out that the inclusion of the complex significantly increases the stability of POPC LUV. PMID- 22051022 TI - Strain, stress and energy in lipid bilayer induced by electrostatic/electrokinetic forces. AB - Lipid bilayer was deformed by the electrostatic/electrokinetic forces induced by the fixed charges on the top monolayer-solution interface. The strains, stresses and energy were simulated using finite element method. The elastic moduli of the heads were four times greater than those of tails sections, but were individually isotropic. The physics of the situation was evaluated using a coupled system of linear elastic equations and electrostatic-electrokinetic (Poisson-Nernst-Planck) equations. The Coulomb force (due to fixed charges in the electric field), and the dielectric force (due to uneven electric field and the solution-membrane permittivity mismatch) bend the membrane, but unevenly. Whereas the bottom monolayer extends vertically (towards charged surface), the top monolayer compresses. In contrast the top monolayer extends horizontally, but the bottom monolayer compresses. The horizontal normal stress is higher in the heads than in the tails sections, but is similar in two monolayers, whereas the vertical normal stress is small. The horizontal normal stress is associated with horizontal normal strain, and vertical with both vertical and horizontal strain. Surprisingly, the shear stress (an indicator where the membrane will deform), is greater in the tails sections. Finally, the elastic energy (which is clearly greater in the heads sections) is dominated by its horizontal component and peaks in the middle of the membrane. The shear component dominates in the tails sections, and is minimal in the membrane center. Even spatially uniform external force thus leads to complex membrane deformation and generates complex profiles of stress and elastic energy. PMID- 22051024 TI - Canine neurogenic Keratoconjunctivitis sicca: 11 cases (2006-2010). AB - OBJECTIVE: To describe the clinical data of dogs with neurogenic Keratoconjunctivitis sicca (KCS) and an ipsilateral dry nose without other neurologic deficits. PROCEDURE: The retrospective case study included 11 dogs diagnosed with neurogenic KCS and an ipsilateral dry nose between 2006 and 2010. Medical records were reviewed for breed, age, sex, history, suspected cause of neurogenic KCS, clinical signs, and treatment modalities. Follow-up information was obtained by re-examination of patients or completion of a telephone survey with the referring veterinarian or the owners. RESULTS: Mean age of the dogs was 6.6 +/- 4.5 years. Neurogenic KCS was diagnosed in three females, five spayed females, one male, and two castrated males representing 10 different breeds. Ophthalmic signs of KCS (mean Schirmer tear test [STT] value of 1.9 +/- 2.9 mm/min) combined with an ipsilateral dry nose were diagnosed in seven left and four right eyes. The suspected cause of neurogenic KCS was idiopathic in nine and trauma in two cases. Systemic therapy consisted of oral pilocarpine 1-2% eye drops combined with case-specific topical treatment with cyclosporine 0.2% and tear substitutes. Duration of systemic treatment with pilocarpine until healing was 125 days (range 84-204, median 98 days) for five dogs. One dog was lost to follow-up, and the remaining five dogs are still under systemic treatment with pilocarpine. CONCLUSIONS: Neurogenic KCS with an ipsilateral dry nose seems to be a predominantly idiopathic disease of middle-aged female dogs without breed predisposition, which may be self-limiting in some cases. PMID- 22051025 TI - Assessment of lateral line function: a potential technique for studies in ototoxicity. AB - In zebrafish neuromast hair cells, the process of programmed cell death ototoxic damage is strikingly similar to that of degenerating hair cells of the mammalian organ of Corti. Therefore, in vivo zebrafish assays involving the lateral line have been developed for drug ototoxicity screening. This is accomplished by examination of canal neuromast morphology in treated larvae using fluorescent dyes. To-date however, physiological confirmation of lateral line dysfunction resulting from such ototoxins has not been reported in the scientific literature- neither for larval nor adult zebrafish. Here we describe a rapid, non-invasive far-field electrophysiological method for assessing lateral line function. We suggest that ototoxic and otoprotective agents identified in larval studies may be assessed using this tool in adult fish. In this way, potential drug candidates can be further screened en route to testing in mammalian models, before potential clinical trials begin. PMID- 22051026 TI - Meningoencephalitis or meningitis in relapsing polychondritis: four case reports and a literature review. AB - Relapsing polychondritis (RP) is a rare autoimmune disease that affects cartilage throughout the body, causing episodic and progressive inflammation. Although rare, RP has diverse acute and subacute nervous system complications, which may sometimes precede systemic manifestations. Here, we report four patients with RP who presented with meningoencephalitis or meningitis without infectious aetiology. In addition, we review the literature for this disease with regard to clinical manifestations and treatment options. PMID- 22051027 TI - Psychogenic non-epileptic seizures: a challenging entity. AB - Psychogenic non-epileptic seizures (PNES) are commonly encountered in neurologic practice. They are often misdiagnosed as epileptic seizures and treated as such for several years before a correct diagnosis is established. Such a misdiagnosis has the potential to expose patients to undue risk through several anti-epileptic drugs (AEDs). Patients are also affected in other ways, such as by financial consequences and the limitation of certain daily activities. In this review, we present the contemporary opinion of PNES with attention to clinically relevant salient features and management strategies. PMID- 22051023 TI - Computational studies of membrane proteins: models and predictions for biological understanding. AB - We discuss recent progresses in computational studies of membrane proteins based on physical models with parameters derived from bioinformatics analysis. We describe computational identification of membrane proteins and prediction of their topology from sequence, discovery of sequence and spatial motifs, and implications of these discoveries. The detection of evolutionary signal for understanding the substitution pattern of residues in the TM segments and for sequence alignment is also discussed. We further discuss empirical potential functions for energetics of inserting residues in the TM domain, for interactions between TM helices or strands, and their applications in predicting lipid-facing surfaces of the TM domain. Recent progresses in structure predictions of membrane proteins are also reviewed, with further discussions on calculation of ensemble properties such as melting temperature based on simplified state space model. Additional topics include prediction of oligomerization state of membrane proteins, identification of the interfaces for protein-protein interactions, and design of membrane proteins. This article is part of a Special Issue entitled: Protein Folding in Membranes. PMID- 22051028 TI - Surgery for paediatric thoracic outlet syndrome. AB - The effectiveness of operative treatment of paediatric thoracic outlet syndrome (TOS) has been analysed, and an attempt made to improve the definition of the condition in terms of presentation, aetiology and diagnosis. A retrospective review of postoperative pain, functional capability and overall outcome was carried out on 13 patients (<18 years) treated by a single surgeon. In 20 operations, 17 were scalenotomies, and three were transaxillary rib resections (TARRs). Follow-up was 6-96 months post-operatively. Surgery alleviated many TOS symptoms, especially vascular compromise, although pain resolution was inconsistent and that of motor deficit poor. Mean functional improvement was good, and overall operative outcomes excellent. Therefore, surgery was successful for paediatric TOS in this series. Anatomical anomalies and sport participation may be related to early onset of TOS in many paediatric patients. PMID- 22051029 TI - Factors associated with anxiety and depression in the management of acoustic neuroma patients. AB - The objectives of this study were to describe anxiety and depression levels among acoustic neuroma patients; examine differences in anxiety and depression across the acoustic neuroma management options of microsurgery, radiation and observation; and to investigate management, medical and demographic factors that might predict anxiety and depression in this patient group. A cross-sectional questionnaire was completed by 205 adults diagnosed with, or treated for, a unilateral acoustic neuroma within five years of questionnaire distribution. Median age of participants was 57.0 years, and 120 (58.5%) were female. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Clinically significant anxiety was reported by 29.8% of participants and 10.2% were depressed. Mean anxiety and depression scores did not differ from general population norms. No significant differences in anxiety and depression were found across management options. Time since management, number of symptoms and comorbid medical conditions predicted anxiety, while depression was predicted by number of symptoms. This appears to be the first study among acoustic neuroma patients in which anxiety and depression were compared across management options. Treating physicians should be aware that as the number of acoustic neuroma symptoms increases, so may the likelihood of clinically significant anxiety and depression. PMID- 22051030 TI - Right temporal variant frontotemporal dementia with motor neuron disease. AB - Patterns of atrophy in frontotemporal dementia (FTD) correlate with the clinical subtypes of behavioral variant FTD (bvFTD), semantic dementia, progressive non fluent aphasia (PNFA) and FTD with motor neuron disease (FTD-MND). Right temporal variant FTD is associated with behavioral dyscontrol and semantic impairment, with tau abnormalities more common in right temporal bvFTD and TDP-43 accumulation in right temporal semantic dementia. However, no clinical and anatomical correlation has been described for patients with predominant right temporal atrophy and FTD-MND. Therefore, we performed a database screen for all patients diagnosed with FTD-MND at Mayo Clinic and reviewed their MRI scans to identify those with striking, dominant, right temporal lobe atrophy. For cases with volumetric MRI we performed voxel based morphometry and for those with brain tissue we performed pathological examination. Of three such patients identified, each patient had different presenting behavioral and/or aphasic characteristics. MRI, including diffusion tensor imaging in one patient, and FDG positron emission tomography revealed striking and dominant right temporal lobe atrophy, right corticospinal tract degeneration, and right temporal hypometabolism. Archived brain tissue was available in two patients; both demonstrating TDP-43 type 3 pathology (Mackenzie scheme) with predominant neuronal cytoplasmic inclusions. In one case, neurofibrillary tangles (Braak V) and neuritic plaques were also present in keeping with a diagnosis of Alzheimer's disease. There appears to be an association between FTD-MND and severe right temporal lobe atrophy. Until further characterization of such cases are determined, they may be best classified as right temporal variant FTD-MND. PMID- 22051031 TI - Postlaminectomy synovial cyst formation: a possible consequence of ligamentum flavum excision. AB - Ligamentum flavum is generally resected with impunity when a laminectomy is performed; it is a strong ligament and its removal may not be inconsequential. We sought to examine the consequence of resection of ligamentum flavum as it pertains to the formation of synovial cysts. Following IRB approval, we retrospectively reviewed the charts of consecutive patients who underwent a laminectomy for any diagnosis during the years 2009-2010. Exclusions were made for patients undergoing resection of a synovial cyst, laminectomy done as part of a fusion, and microdiscectomy. A total of 201 laminectomies were performed. 10 instances of post-laminectomy synovial cyst occurred in only the lumbar spine. Synovial cysts occurred exclusively after surgery for stenosis (n=10). Laminectomy and resection of the ligament flavum is a risk factor for the subsequent formation of a synovial cyst. Secondary synovial cyst formation should be suspected in individuals who develop radiculopathy after laminectomy for stenosis. PMID- 22051032 TI - Cerebrovascular bypass and aneurysm trapping for the treatment of an A2-segment anterior cerebral artery pseudoaneurysm and herniation through a skull base defect following trauma. AB - Fractures of the anterior skull base can lead to pseudoaneurysm formation as a result of direct injury to a vessel wall. Pseudoaneurysms in this location are challenging to treat, as both perforator and distal blood supply must be maintained. Additionally, traumatic skull base fractures can lead to a rare condition of cerebral blood vessel herniation through the bony defect, further complicating treatment planning. Treatment of these lesions is essential to (1) prevent the occurrence of potentially fatal subarachnoid hemorrhage and (2) prevent dissection from propagating and compromising blood flow to distal vessels, perforators, and even parent vessels. We present a unique case of a traumatic proximal anterior cerebral artery pseudoaneurysm, herniating through a skull base defect. Treatment consisted of aneurysm trapping and bypass with skull base reconstruction. PMID- 22051033 TI - ALOX5AP genetic variants and risk of atherothrombotic stroke in the Taiwanese population. AB - We explored the role of variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene as factors for atherothrombotic stroke (ATS). A HapMap based haplotype-tagging single nucleotide polymorphism (htSNP) association study was conducted in an isolated Taiwanese population. Multivariate logistic regression analyses revealed that patients with the GG/CG genotype of rs4293222 and the AA/AG genotype of rs4360791 had a 1.61-fold (odds ratio [OR]=1.61; 95% confidence interval [CI]=1.02-2.56, p=0.042) and a 1.69-fold (OR=1.69; 95% CI=1.00-2.86, p=0.047) increased risk of ATS, compared with patients with the CC/GG genotype, respectively. The most common haplotype allele, GTA, was used as a reference when analyzing the association between the haplotypes related to rs4293222, rs10507391, rs12429692 and ATS. The combined frequencies of all minor variant alleles of the three selected htSNP were associated with a 44% decreased risk of ATS (OR=0.56; 95% CI=0.37-0.84, p=0.005). This study provides preliminary evidence suggesting that genetic polymorphisms of ALOX5AP are associated with ATS. PMID- 22051034 TI - Unusual variants of midline nasal dermoid cysts: a series of three cases. AB - OBJECTIVE: Dermoids presenting in early life with a sinus tract along the midline of the nasal dorsum are well described. We present three very unusual variants of this condition. METHODS: Case one was a two-year-old child with a pit in the philtrum of the lip. The tract pierced the nasal spine and extended towards the crista galli. Case two was a 15-month-old child with two separate sinus openings on the dorsum, one below and one above a dermoid cyst. Case three was a 17-year old adolescent with neurological disability. Scanning showed a dermoid cyst deep in the anterior skull base, but the sinus tract had been obliterated by bony overgrowth due to long term use of antiepileptic medication. RESULTS: Cases one and two were successfully managed by complete excision via an external rhinoplasty approach. Case three, in contrast, was not operated upon due to bony obliteration of the sinus tract. CONCLUSION: Surgeons dealing with nasal dermoids must be able to adapt to the variable anatomical and clinical features of these lesions. PMID- 22051035 TI - Z dependence of electron scattering by single atoms into annular dark-field detectors. AB - A simple parameterization is presented for the elastic electron scattering cross sections from single atoms into the annular dark-field (ADF) detector of a scanning transmission electron microscope (STEM). The dependence on atomic number, Z, and inner reciprocal radius of the annular detector, q(0), of the cross section sigma(Z,q(0)) is expressed by the empirical relation [see formula in text] where A(q(0)) is the cross section for hydrogen (Z = 1), and the detector is assumed to have a large outer reciprocal radius. Using electron elastic scattering factors determined from relativistic Hartree-Fock simulations of the atomic electron charge density, values of the exponent n(Z,q(0)) are tabulated as a function of Z and q(0), for STEM probe sizes of 1.0 and 2.0 A. Comparison with recently published experimental data for single-atom scattering [Krivanek et al. (2010). Nature 464, 571-574] suggests that experimentally measured exponent values are systematically lower than the values predicted for elastic scattering from low-Z atoms. It is proposed that this discrepancy arises from the inelastic scattering contribution to the ADF signal. A simple expression is proposed that corrects the exponent n(Z,q(0)) for inelastic scattering into the annular detector. PMID- 22051036 TI - Dental injuries with kick-scooters in 6- to 12-year-old children. AB - BACKGROUND/AIM: The objective of this study was to investigate the occurrence of injuries, especially dental trauma, in scooter-related accidents. In addition, children's habits of wearing protective gear were assessed. MATERIAL AND METHODS: The study was conducted in primary schools in three neighboring towns near Basel, Switzerland, using anonymous multiple-choice questionnaires completed by parents of schoolchildren. RESULTS: A total of 953 scooter riders were included in the study. The average age was 9.1 years (range 6-12 years). Of riders, 58.3% wore no protective gear, 39.6% wore a helmet, and 2% wore other protective equipment. Twenty-nine percentage of the children have sustained an accident while riding the scooter, of those injuries, 41.4% affected the lower extremities, 37.0% the upper extremities, 21.6% the head, and 11.2% dental injuries; 20.3% of accidents required medical treatment. CONCLUSIONS: Parents, teachers, and doctors should be aware of the dangers involved in scooter riding. Educational measures, especially concerning use of protective gear, should be implemented to reduce the number and severity of injuries caused by this popular recreational activity. PMID- 22051037 TI - 31P-MR spectroscopy in monozygotic twins discordant for schizophrenia or schizoaffective disorder. PMID- 22051038 TI - Massive sedimentation of fine sediment with organic matter and enhanced benthic pelagic coupling by an artificial dyke in semi-enclosed Chonsu Bay, Korea. AB - To assess the impact of an artificial dyke in Chonsu Bay (CBD) on the organic carbon (C(org)) cycle, we measured excess (210)Pb activities, C(org) and nitrogen content in sediment cores. The C(org) oxidation rates (C(ox)) on the surface sediment and benthic nutrient fluxes were also quantified with an in situ benthic chamber. The higher excess (210)Pb inventory, C(org) and nitrogen in cores near the CBD indicated lateral transport and local, massive deposition of particulate matter due to tidal circulation altered by artificial dyke construction. The C(ox) in sediment near the CBD was about twice as high as that out of the bay, suggesting the importance of benthic remineralization of organic matter. The benthic fluxes of dissolved inorganic nitrogen and phosphate were four to six times higher than those outside the bay, corresponding to 141% and 131% respectively, of the requirements for primary production. PMID- 22051039 TI - Marine debris impacts to a tidal fringing-marsh in North Carolina. AB - We evaluated injuries to Spartina alterniflora by debris items common to North Carolina coastal waters as a function of debris type (wire blue crab pots, vehicle tires, and anthropogenic wood) and deployment duration, and monitored S. alterniflora recovery following debris removal. Injuries sustained by S. alterniflora and subsequent recovery, varied considerably between debris types. Differences were likely due to dissimilarities in the structure and composition of debris. Tires caused an immediate (within 3 weeks) and long-term impact to S. alterniflora; tire footprints remained devoid of vegetation 14 months post removal. Conversely, crab pot impacts were not as abrupt and recovery was short term (<10 months). We suggest that removal programs specifically target habitats that are susceptible to negative impacts (e.g., salt marsh) and prone to debris accumulation. Management would benefit from the inclusion of habitat information in removal databases. PMID- 22051040 TI - Response of ERbeta and aromatase expression in the monkey hippocampal formation to ovariectomy and menopause. AB - Changes in the expression of estrogen-related substances in monkeys' brains at the menopausal transition, when estrogen deficit starts to occur, have not yet been examined thoroughly. In the present study, we immunohistochemically investigated the expression levels of estrogen receptor beta (ERbeta) and aromatase (local estrogen synthesizing enzyme) in the hippocampal formation of premenopausal, menopausal, and ovariectomized premenopausal monkeys. In all monkeys tested, ERbeta immunoreactivity was observed in interneurons located in the subiculum and the Ammon's horn, and most of these ERbeta-immunoreactive neurons coexpressed a GABAergic neuron marker, parvalbumin. In the menopausal monkeys who exhibited a decline in estrogen concentration, hippocampal ERbeta was highly upregulated, while aromatase expression was not markedly changed. By contrast, aromatase in the ovariectomized monkeys was significantly upregulated, while ERbeta expression was not changed. In the brains of ovariectomized and menopausal monkeys, depletion of ovary-derived estrogen brought about different reactions which may be attributed to the senescence of brain aging. PMID- 22051041 TI - An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells. AB - BACKGROUND: Acquisition of drug-resistance in cancer has led to treatment failure, however, their mechanisms have not been clarified yet. Recent observations indicated that aberrant expressed microRNA (miRNA) caused by chromosomal alterations play a critical role in the initiation and progression of cancer. Here, we performed an integrated genomic analysis combined with array based comparative hybridization, miRNA, and gene expression microarray to elucidate the mechanism of drug-resistance. RESULTS: Through genomic approaches in MCF7-ADR; a drug-resistant breast cancer cell line, our results reflect the unique features of drug-resistance, including MDR1 overexpression via genomic amplification and miRNA-mediated TP53INP1 down-regulation. Using a gain of function study with 12 miRNAs whose expressions were down-regulated and genome regions were deleted, we show that miR-505 is a novel tumor suppressive miRNA and inhibits cell proliferation by inducing apoptosis. We also find that Akt3, correlate inversely with miR-505, modulates drug sensitivity in MCF7-ADR. CONCLUSION: These findings indicate that various genes and miRNAs orchestrate to temper the drug-resistance in cancer cells, and thus acquisition of drug resistance is intricately controlled by genomic status, gene and miRNA expression changes. PMID- 22051042 TI - Congenital stationary night blindness is associated with the leopard complex in the Miniature Horse. AB - OBJECTIVE: To determine if congenital stationary night blindness (CSNB) exists in the Miniature Horse in association with leopard complex spotting patterns (LP), and to investigate if CSNB in the Miniature Horse is associated with three single nucleotide polymorphisms (SNPs) in the region of TRPM1 that are highly associated with CSNB and LP in Appaloosas. ANIMALS STUDIED: Three groups of Miniature Horses were studied based on coat patterns suggestive of LP/LP (n=3), LP/lp (n=4), and lp/lp genotype (n=4). PROCEDURES: Horses were categorized based on phenotype as well as pedigree analysis as LP/LP, LP/lp, and lp/lp. Neurophthalmic examination, slit-lamp biomicroscopy, indirect ophthalmoscopy, and scotopic flash electroretinography were performed on all horses. Hair samples were processed for DNA analysis. Three SNPs identified and associated with LP and CSNB in the Appaloosa were investigated for association with LP and CSNB in these Miniature Horses. RESULTS: All horses in the LP/LP group were affected by CSNB, while none in the LP/lp or lp/lp groups were affected. All three SNPs were completely associated with LP genotype (chi(2) = 22, P << 0.0005) and CSNB status (chi(2) =11, P<0.0005). CONCLUSIONS: The Miniature Horse breed is affected by CSNB and it appears to be associated with LP as in the Appaloosa breed. The SNPs tested could be used as a DNA test for CSNB until the causative mutation is determined. PMID- 22051043 TI - Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. AB - Oxidative stress has been implicated in the pathogenesis of cardiovascular diseases, including myocardial hypertrophy and infarction. Although impairment of antioxidant defense mechanisms has been thought to provoke oxidative stress induced myocardial dysfunction, it has been difficult to clearly demonstrate. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive, basic leucine zipper protein that regulates the transcription of several antioxidant genes. We previously reported that sustained activation of Nrf2 upregulates transcription of a number of endogenous antioxidants in the heart. Here, we show that acute exercise stress (AES) results in activation of Nrf2/ARE (antioxidant response element) signaling and subsequent enhancement of antioxidant defense pathways in wild-type (WT) mouse hearts, while oxidative stress, along with blunted defense mechanisms, was observed in Nrf2-/- mice. We also find that AES is associated with increased trans-activation of ARE-containing genes in exercised animals when compared to age-matched sedentary WT mice. However, enhanced oxidative stress in response to AES was observed in Nrf2-/- mice due to lower basal expression and marked attenuation of the transcriptional induction of several antioxidant genes. Thus, AES induces ROS and promotes Nrf2 function, but disruption of Nrf2 increases susceptibility of the myocardium to oxidative stress. Our findings suggest the basis for a nonpharmacological approach to activate Nrf2/ARE signaling, which might be a potential therapeutic target to protect the heart from oxidative stress-induced cardiovascular complications. PMID- 22051044 TI - Preoperative management in patients with single-ventricle physiology. AB - OBJECTIVE: Advancements in the preoperative management of patients with single ventricle physiology continue to evolve. Previous reports have questioned the benefit of using inhaled nitrogen in single-ventricle patients, suggesting that this therapeutic modality may not provide adequate systemic cardiac output. The objective of this study was to review our institutional experience managing preoperative patients with single-ventricle physiology using a combination of afterload reduction and inhaled hypoxemic therapy. DESIGN, SETTING, AND PATIENTS: This is a retrospective review of 49 consecutive single-ventricle patients admitted preoperatively between July 2004 and January 2009, to the cardiac intensive care unit at Children's Hospital of Pittsburgh who underwent single ventricle palliation, and treated preoperatively with milrinone and inhaled nitrogen. Therapeutic interventions and indirect indicators of cardiac output were collected on day of admission (time 0) and compared with those collected on the morning of surgery (time 1); data included clinical assessment, hemodynamic measurements, and laboratory values. RESULTS: When comparing time 0 to time 1, there was a statistically significant decrease in lactate (from 2.2 to 1.8 mEq/L [P < 0.001]) and an increase in pH (from 7.36 to 7.41 [P < 0.001]), serum bicarbonate (from 24.16 to 27.55 mmol/L [P < 0.001]) and arterial PaO2 (from 38.10 to 41.82 mm Hg [P = 0.027]). Preoperatively, there were no deaths, and only two patients had an evidence of multiorgan dysfunction on day of surgery (time 1). CONCLUSION: Our results suggest that a combination of afterload reduction and hypoxemic therapy was able to maintain an appropriate distribution of the cardiac output in the majority of preoperative patients with single-ventricle physiology. An adequate balance of systemic and pulmonary blood flow was successfully achieved with an increase in arterial PaO2 values. PMID- 22051045 TI - Plasticity of TGF-beta signaling. AB - BACKGROUND: The family of TGF-beta ligands is large and its members are involved in many different signaling processes. These signaling processes strongly differ in type with TGF-beta ligands eliciting both sustained or transient responses. Members of the TGF-beta family can also act as morphogen and cellular responses would then be expected to provide a direct read-out of the extracellular ligand concentration. A number of different models have been proposed to reconcile these different behaviours. We were interested to define the set of minimal modifications that are required to change the type of signal processing in the TGF-beta signaling network. RESULTS: To define the key aspects for signaling plasticity we focused on the core of the TGF-beta signaling network. With the help of a parameter screen we identified ranges of kinetic parameters and protein concentrations that give rise to transient, sustained, or oscillatory responses to constant stimuli, as well as those parameter ranges that enable a proportional response to time-varying ligand concentrations (as expected in the read-out of morphogens). A combination of a strong negative feedback and fast shuttling to the nucleus biases signaling to a transient rather than a sustained response, while oscillations were obtained if ligand binding to the receptor is weak and the turn-over of the I-Smad is fast. A proportional read-out required inefficient receptor activation in addition to a low affinity of receptor-ligand binding. We find that targeted modification of single parameters suffices to alter the response type. The intensity of a constant signal (i.e. the ligand concentration), on the other hand, affected only the strength but not the type of the response. CONCLUSIONS: The architecture of the TGF-beta pathway enables the observed signaling plasticity. The observed range of signaling outputs to TGF beta ligand in different cell types and under different conditions can be explained with differences in cellular protein concentrations and with changes in effective rate constants due to cross-talk with other signaling pathways. It will be interesting to uncover the exact cellular differences as well as the details of the cross-talks in future work. PMID- 22051046 TI - Novel metabolic biomarkers related to sulfur-dependent detoxification pathways in autistic patients of Saudi Arabia. AB - BACKGROUND: Xenobiotics are neurotoxins that dramatically alter the health of the child. In addition, an inefficient detoxification system leads to oxidative stress, gut dysbiosis, and immune dysfunction. The consensus among physicians who treat autism with a biomedical approach is that those on the spectrum are burdened with oxidative stress and immune problems. In a trial to understand the role of detoxification in the etiology of autism, selected parameters related to sulfur-dependent detoxification mechanisms in plasma of autistic children from Saudi Arabia will be investigated compared to control subjects. METHODS: 20 males autistic children aged 3-15 years and 20 age and gender matching healthy children as control group were included in this study. Levels of reduced glutathione (GSH), total (GSH+GSSG), glutathione status (GSH/GSSG), glutathione reductase (GR), glutathione- s-transferase (GST), thioredoxin (Trx), thioredoxin reductase (TrxR) and peroxidoxins (Prxs I and III) were determined. RESULTS: Reduced glutathione, total glutathione, GSH/GSSG and activity levels of GST were significantly lower, GR shows non-significant differences, while, Trx, TrxR and both Prx I and III recorded a remarkably higher values in autistics compared to control subjects. CONCLUSION: The impaired glutathione status together with the elevated Trx and TrxR and the remarkable over expression of both Prx I and Prx III, could be used as diagnostic biomarkers of autism. PMID- 22051047 TI - The contribution of pain and depression to self-reported sleep disturbance in patients with rheumatoid arthritis. AB - The objective of this article is to assess the contribution of disease activity, pain, and psychological factors to self-reported sleep disturbance in patients with rheumatoid arthritis (RA), and to evaluate whether depression mediates the effects of pain on sleep disturbance. The sample included 106 patients with confirmed RA who participated in an assessment of their disease activity, pain, psychological functioning, and sleep disturbance during a baseline evaluation prior to participating in a prospective study to help them manage their RA. Self measures included the Rapid Assessment of Disease Activity in Rheumatology, the SF-36 Pain Scale, the Helplessness and Internality Subscales of the Arthritis Helplessness Index, the Active and Passive Pain Coping Scales of the Pain Management Inventory, the Center for Epidemiological Studies Depression Scale, and the Pittsburgh Sleep Quality Index. Hierarchical multiple regression analysis confirmed that higher income, pain, internality, and depression contributed independently to higher sleep disturbance. A mediational analysis demonstrated that depression acted as a significant mechanism through which pain contributed to sleep disturbance. Cross-sectional findings indicate that pain and depression play significant roles in self-reported sleep disturbance among patients with RA. The data suggest the importance of interventions that target pain and depression to improve sleep in this medical condition. PMID- 22051048 TI - Suppression of the maturation and activation of the dendritic cell line DC2.4 by melanoma-derived factors. AB - Dendritic cells play critical roles in both innate and adaptive immunity, and their numerous functions are tightly linked to their maturation and activation status. Here, we characterize the murine dendritic cell line DC2.4 as a model for studying dendritic cell maturation and activation, and we evaluate the influence of melanoma tumor cells on these processes. Exposure of DC2.4 cells to the Toll like receptor ligand lipopolysaccharide induces both maturation and activation of these cells, characterized by upregulation of costimulatory molecule expression and proinflammatory cytokine/chemokine production. This maturation and activation is suppressed by soluble factors derived from both the highly tumorigenic B16-F1 and the poorly tumorigenic D5.1G4 murine melanoma cell lines. Interestingly, the extent of DC2.4 immunosuppression by these melanomas correlates with their tumorigenicity, suggesting a potentially vital role for dendritic cell/tumor cell interactions in the regulation of anti-tumor immunity and tumor outgrowth. PMID- 22051049 TI - Disruption of HIF-1alpha in hepatocytes impairs glucose metabolism in diet induced obesity mice. AB - The liver plays a central role in glucose homeostasis in the whole-body by responding to environmental factors including nutrients, hormones, and oxygen. In conditions of metabolic overload such as diabetes mellitus and obesity, coordinated regulation between oxygen supply and consumption has been reported to be disrupted and subsequently cause tissue hypoxia, although pathological significance of the disease-related hypoxia remains elusive. To investigate the role of tissue hypoxia in the liver on systemic glucose homeostasis, mice lacking HIF-1alpha gene, a critical component of a master regulator of hypoxic response, in hepatocytes were exposed to high fat/sucrose diet (HFSD). Exposure to HFSD for 5 weeks elicited liver hypoxia with a transient increase in HIF-1alpha protein expression in the liver of control mice. Glucose disposal was marginally impaired in control mice when challenged oral glucose tolerance test, but such impairment was enhanced in the mutant mice. This alteration was accompanied by a complete inhibition of glucokinase induction with a significant reduction of hepatic glucose uptake. Mice fed HFSD for 20 weeks exhibited fasting hyperglycemia and glucose intolerance, whereas these metabolic phenotypes deteriorated considerably with severe insulin resistance in skeletal muscles and adipose tissues in the mutant mice. These findings suggest that HIF-1 in hepatocytes plays protective roles against the progression of diabetes mellitus. PMID- 22051050 TI - A new chromosome 14-based human artificial chromosome (HAC) vector system for efficient transgene expression in human primary cells. AB - The use of non-integrating human artificial chromosomes (HACs) in gene therapy possibly allows for safe and reliable genetic modification of human cells without insertional mutagenesis and/or unexpected oncogene activations. Although we previously demonstrated that the HAC provides long-term therapeutic erythropoietin (EPO) production in normal human primary fibroblasts (hPFs), the expression level of EPO was too low to provide medical benefits for human therapy. Thus, the next challenge for the application of this system in therapeutic purposes is to improve the transgene expression on HACs. Here, we newly constructed chromosome 14-based HACs and examined the effects of the telomere and promoter regions on the expression level of the tansgene in hPFs. We showed that the use of natural telomere/sub-telomere and enhancers within the 5' untranslated region of the human ubiquitin C gene greatly increased (over 1000 fold) the EPO production in hPFs. Furthermore, we demonstrated the reprogramming of mouse embryonic fibroblasts by HAC-mediated introduction of four transcription factors, and established induced pluripotent stem cells with no trace of the HACs carrying multiple expression cassettes with large genome fragments. These results indicate that this HAC system could allow us to manipulate multiple transgenes efficiently in human primary cells, providing a promising tool not only for gene therapy but also for investigating genome functions in drug discoveries. PMID- 22051051 TI - Everted third eyelid cartilage in a cat: a case report and literature review. AB - An 8-year-old neutered female British Blue cat was presented with a presumed diagnosis of a prolapsed nictitans gland and associated ocular irritation and epiphora. However, during surgery, the apparent nictitans gland protrusion was determined to be an everted cartilage of the nictitating membrane. The scrolled portion of the cartilage was removed through an incision through the conjunctiva on the bulbar aspect of the third eyelid, as previously described in the dog. This operation resolved the ocular irritation occurring, and the third eyelid returned to its anatomically correct position. PMID- 22051052 TI - Chemical and morphological study of gunshot residue persisting on the shooter by means of scanning electron microscopy and energy dispersive X-ray spectrometry. AB - Persistence of gunshot residue (GSR) simultaneously collected from hands, face and hair, and clothing of the shooting person was examined. Samples were collected from five shooters in nine time intervals after a single shoot with a Luger 9 mm pistol, in the range of 0-4 h and examined with scanning electron microscopy and energy dispersive X-ray spectrometry. Numbers of particles, frequencies of occurrence of certain compositions of particles, and their sizes in function of the time intervals were inspected. The greatest numbers of particles were observed in samples collected from hands right after shooting, but they decrease quickly with time. In samples collected from the face smaller initial numbers of particles were found, but they lasted at a similar level longer. The estimated half-life times of particles were less than 1 h for samples taken from the hands, over 1 h for clothing and about 2-3 h for the face. In samples collected at longer intervals after shooting, there were particles present of small sizes and irregular shapes. The results demonstrate that including evidence collected from the suspect's face and hair may increase the probability of detection of GSR in cases when the suspect has not been apprehended immediately after the investigated incident. PMID- 22051053 TI - Biofilm accumulation on endotracheal tubes following prolonged intubation. AB - OBJECTIVE: To demonstrate that patients who have been intubated for prolonged periods of time will have an increased likelihood of developing bacterial biofilm on their endotracheal tubes. METHODS: We collected endotracheal tubes from patients at the time of extubation, and analysed representative sections with scanning electron microscopy for morphologic evidence of biofilms. RESULTS: From September 2007 to September 2008, 32 endotracheal tubes were analysed with electron microscopy. Patients who had been intubated for 6 days or longer had a significantly higher percentage of endotracheal tubes that exhibited bacterial biofilms, compared with patients intubated for less than 6 days (88.9 versus 57.1 per cent, p = 0.0439). CONCLUSIONS: Longer duration of intubation is associated with a higher incidence of bacterial biofilm. Further research is needed to link the presence of bacterial biofilms to acquired laryngotracheal damage. PMID- 22051054 TI - Synthesis, molecular modeling studies and biological evaluation of fluorine substituted analogs of GW 501516. AB - (+/-)-2-Fluoro-2-(2-methyl-4-(((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5 yl)methyl)thio)phenoxy)acetic acid (2a) has been prepared and subjected to biological testing against all three subtypes of the PPARs. This compound exhibited agonist effects with EC(50) values of 560 and 55 nM against PPARalpha and PPARdelta, respectively, in a luciferase assay. Moreover, compound (+/-)-2a also exhibited potent ability to induce oleic acid oxidation in a human myotube cell assay with EC(50)=3.7 nM. Compound (+/-)-2a can be classified as a dual PPARalpha/delta agonist with a 10-fold higher potency against the PPARdelta receptor than against the PPARalpha receptor. Molecular modeling studies revealed that both enantiomers of 2a bind to the PPARdelta receptor with similar binding energies. PMID- 22051055 TI - Effect of early reassessment of antimicrobial prescription on antibiotic use in acute respiratory tract infections. PMID- 22051056 TI - Attenuation of psoriasis-like skin lesion in a mouse model by topical treatment with indirubin and its derivative E804. PMID- 22051057 TI - Top predators as biodiversity regulators: the dingo Canis lupus dingo as a case study. AB - Top-order predators often have positive effects on biological diversity owing to their key functional roles in regulating trophic cascades and other ecological processes. Their loss has been identified as a major factor contributing to the decline of biodiversity in both aquatic and terrestrial systems. Consequently, restoring and maintaining the ecological function of top predators is a critical global imperative. Here we review studies of the ecological effects of the dingo Canis lupus dingo, Australia's largest land predator, using this as a case study to explore the influence of a top predator on biodiversity at a continental scale. The dingo was introduced to Australia by people at least 3500 years ago and has an ambiguous status owing to its brief history on the continent, its adverse impacts on livestock production and its role as an ecosystem architect. A large body of research now indicates that dingoes regulate ecological cascades, particularly in arid Australia, and that the removal of dingoes results in an increase in the abundances and impacts of herbivores and invasive mesopredators, most notably the red fox Vulpes vulpes. The loss of dingoes has been linked to widespread losses of small and medium-sized native mammals, the depletion of plant biomass due to the effects of irrupting herbivore populations and increased predation rates by red foxes. We outline a suite of conceptual models to describe the effects of dingoes on vertebrate populations across different Australian environments. Finally, we discuss key issues that require consideration or warrant research before the ecological effects of dingoes can be incorporated formally into biodiversity conservation programs. PMID- 22051058 TI - Shear bond strength of restorations applied to un-complicated crown fractures: an in vitro study. AB - BACKGROUND: Study was designed to evaluate shear bond strengths of different restorative techniques of uncomplicated enamel-dentin fractures in permanent incisors. MATERIAL AND METHODS: Forty human mandibular incisors were divided into four groups. One-third of their anatomical crowns from the incisal edges were cut off in three groups, representing an uncomplicated enamel-dentin fracture. Intact teeth in group 1 were used as control. In group 2, edge fragments were reattached by flowable composite (Filltek Flowable Supreme XT). In group 3, teeth were restored with universal resin composite (Filtek Z 250). In group 4, pre impregnated glass fiber sheet (everStickNet) was positioned onto fractured surface, and then restorations were completed with resin composite. Three-step etch-and-rinse adhesive system (Adper Scotchbond Multi Purpose) was used in all test groups. Shear bond strengths of all samples were determined in universal testing machine, and data were analyzed with Kruskal-Wallis followed by Mann Whitney U tests. Failure types were observed by light microscope. RESULTS: Shear bond strength of sound teeth was significantly higher than those of restored teeth (P < 0.05). Mean shear bond strengths of the reattached teeth were lower than the other two restoration types; however, differences were not statistically significant (P > 0.05). CONCLUSIONS: Load-bearing capacity of restored teeth was not as high as sound teeth in the uncomplicated crown fracture. However, shear bond strength of different types of restorations seems close to each other. PMID- 22051059 TI - Effects of losartan on whole body, skeletal muscle and vascular insulin responses in obesity/insulin resistance without hypertension. AB - AIMS: Renin-angiotensin system antagonists have been found to improve glucose metabolism in obese hypertensive and type 2 diabetic subjects. The mechanism of these effects is not well understood. We hypothesized that the angiotensin receptor antagonist losartan would improve insulin-mediated vasodilation, and thereby improve insulin-stimulated glucose uptake in skeletal muscle of insulin resistant subjects. METHODS: We studied subjects with obesity and insulin resistance but without hypertension, hypercholesterolaemia or dysglycaemia [age 39.0 +/- 9.6 yr (mean +/- SD), body mass index (BMI) 33.2 +/- 5.9 kg/m(2) , BP 115.8 +/- 12.2/70.9 +/- 7.2 mmHg, LDL 2.1 +/- 0.5 mmol/l]. Subjects were randomized to 12 weeks' double-blind treatment with losartan 100 mg once daily (n = 9) or matching placebo (n = 8). Before and after treatment, under hyperinsulinaemic euglycaemic clamp conditions we measured whole-body insulin stimulated glucose disposal, insulin-mediated vasodilation, and insulin stimulated leg glucose uptake by the limb balance technique. RESULTS: Whole-body insulin-stimulated glucose disposal was not significantly increased by losartan. Insulin-mediated vasodilation was augmented following both treatments [increase in leg vascular conductance: pretreatment 0.7 +/- 0.3 l/min/mmHg (losartan, mean +/- SEM) and 0.9 +/- 0.3 (placebo), posttreatment 1.0 +/- 0.4 (losartan) and 1.3 +/- 0.6 (placebo)] but not different between treatment groups (p = 0.53). Insulin's action to augment nitric oxide (NO) production and to augment endothelium-dependent vasodilation was also not improved. Leg glucose uptake was not significantly changed by treatments, and not different between groups (p = 0.11). CONCLUSIONS: These findings argue against the hypothesis that losartan might improve skeletal muscle glucose metabolism by improving insulin-mediated vasodilation in normotensive insulin-resistant obese subjects. The metabolic benefits of angiotensin receptor blockers may require the presence of hypertension in addition to obesity-associated insulin resistance. PMID- 22051060 TI - The ORF3-encoded proteins of vitiviruses GVA and GVB induce tubule-like and punctate structures during virus infection and localize to the plasmodesmata. AB - The genomic RNA of vitiviruses contains 5 open reading frames (ORF). ORF3 encodes a protein to which the function of a movement protein (MP) was assigned, based on sequence homology with other viral proteins. The aim of the research described in this paper was to gain further insight in distribution profile of the ORF3 product encoded by the vitiviruses Grapevine virus A (GVA) and Grapevine virus B (GVB). Expression of the GVA MP-GFP fusion protein via the virus genome in Nicotiana benthamiana leaves resulted in the formation of irregular spots and fibrous network structures on the outermost periphery of epidermal cells. Expression of GVA MP-GFP and GVB MP-GFP was involved in the formation of the tubule-like and punctate structures on the periphery of N. benthamiana and Vitis vinifera protoplasts. Co-expression of the GVA MP-GFP and GVA MP-RFP in protoplasts resulted in co-localization of these proteins into the same punctate structures, indicating that the MP is not accumulated randomly onto the cell surface, but targeted to particular sites at the cell periphery, where punctate and tubule-like structures are likely formed. With the use of cytoskeleton and secretory pathway inhibitors, we showed that the cytoskeletal elements are not likely to be involved in targeting of the MP-GFP to the punctate cellular structures. In addition to MP, a functional coat protein was found to be essential for virus spread within inoculated leaves. PMID- 22051061 TI - Apoptosis, mastocytosis, and diminished adipocytokine gene expression accompany reduced epididymal fat mass in long-standing diet-induced obese mice. AB - BACKGROUND: Obesity is characterized by increased cell death and inflammatory reactions in the adipose tissue. Here, we explored pathophysiological alterations taking place in the adipose tissue in long-standing obesity. In the epididymal fat of C57BL/6 mice fed a high-fat diet for 20 weeks, the prevalence and distribution of dead adipocytes (crown-like structures), mast cells (toluidine blue, mMCP6), macrophages (F4/80), and apoptotic cells (cleaved caspase-3) were measured. Moreover, gene and/or protein expression of several adipocytokines (leptin, adiponectin, TNF-alpha, IL-10, IL-6, MCP-1), F4/80, mMCP6, cleaved caspase-3 were determined. RESULTS: We observed that the epididymal fat mass was lower in obese than in lean mice. In obese mice, the epididymal fat mass correlated inversely with body weight and liver mass. Dead adipocytes, mast cells, macrophages, and apoptotic cells were abundant in the epididymal fat of obese mice, especially in the rostral vs. caudal zone. Accordingly, mMCP6, F4/80, and cleaved caspase-3 gene and/or protein expression was increased. Conversely, adiponectin, leptin, IL-6, and MCP-1 gene expression levels were lower in the epididymal fat of obese than lean mice. Although TNF-alpha and IL-10 gene expression was higher in the epididymal fat of obese mice, their expression relative to F4/80 and mMCP6 expression were lower in the heavily infiltrated rostral than caudal zone. CONCLUSIONS: This study demonstrates that in mice with long-standing obesity diminished gene expression of several adipocytokines accompany apoptosis and reduced mass of the epididymal fat. Our findings suggest that this is due to both increased prevalence of dead adipocytes and altered immune cell activity. Differential distribution of metabolically challenged adipocytes is indicative of the presence of biologically diverse zones within the epididymal fat. PMID- 22051063 TI - Synthesis and kinetic testing of new inhibitors for a metallo-beta-lactamase from Klebsiella pneumonia and Pseudomonas aeruginosa. AB - There are currently no clinically useful inhibitors against metallo-beta lactamases (MBLs), enzymes that confer resistance against a broad spectrum of commonly used antibiotics and that are produced by an increasing number of bacterial pathogens. New pyrrole derivatives were synthesized and assayed for their inhibitory effect on the catalytic activity of the IMP-1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Six compounds tested (3a-3c, 5, 7 and 8) show micromolar inhibition constants (K(i) values range from ~10 to 30 MUM). In silico docking was employed to investigate the binding mode of the strongest inhibitor, 3b, in the active site of IMP-1. Implications for further improvements of binding efficiency and specificity are discussed. PMID- 22051062 TI - Astrocytic responses in the lateral geniculate nucleus of monkeys with experimental glaucoma. AB - OBJECTIVE: To investigate the responses of lateral geniculate nucleus (LGN) astrocytes to experimental glaucoma in monkeys. ANIMAL STUDIED: Rhesus monkeys (Macaca mulatta). PROCEDURES: Unilateral chronic elevation of intraocular pressure (IOP) was induced in six rhesus monkeys by laser photocoagulation of the trabecular meshwork. Four normal monkeys were used as controls. Immunohistochemistry with antibodies to glial fibrillary acidic protein (GFAP), S100beta and parvalbumin was used to specifically label astrocytes and neurons in the LGN. The relative immunointensity (RI) of GFAP was defined as the ratio of intensity between each region of interest to a reference field and compared between the experimental and control groups as a function of percentage optic nerve fiber loss. Ultrastructural changes of LGN astrocytes were examined by transmission electron microscopy. RESULTS: An increase in GFAP and S100beta immunoreactivity was observed in the LGN layers receiving projections from the experimental glaucoma eyes. Quantitative analysis revealed that the RI of GFAP in both the magnocellular and parvocellular layers connected to the glaucomatous eyes increased in a linear fashion with increasing optic nerve fiber loss. Compared to controls, the RI of GFAP was also moderately elevated in LGN layers connected to the fellow nonglaucomatous eyes. Ultrastructurally, accumulation of glial filaments that occurred throughout the perikaryon and extended into the process in reactive astrocytes was observed in LGN layers of glaucomatous monkeys. CONCLUSIONS: Reactive astrogliosis occurs in the magnocellular and parvocellular LGN layers of monkeys with unilateral glaucoma. Astrocytes may play an important role in the regulation of LGN microenvironment in glaucoma. PMID- 22051064 TI - Copper(II) chloride mediated synthesis and DNA photocleavage activity of 1 aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3-a]quinoxalines. AB - A new class of photonucleases, 1-aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3 a]quinoxalines (4) was synthesized in a facile and efficient manner via copper(II) chloride mediated oxidative intramolecular cyclization of 2 (arylidenehydrazino)-3-substituted-quinoxalines (3). DNA cleavage potency of compounds 4a-d (40 MUg each) was quantitatively evaluated on supercoiled plasmid PhiX174 under UV irradiation (312 nm, 15 W) without any additive. Compound 4c was found to be the most efficient DNA photocleaver which had converted supercoiled DNA (form I) into the relaxed DNA (form II) at 30 MUg and the DNA photocleavage activity increases with increase in concentration of 4c. PMID- 22051065 TI - Synthesis and biological activity of novel N-cycloalkyl-(cycloalkylaryl)-2-[(3-R 2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides. AB - In this paper the novel N-cycloalkyl-(cycloalkylaryl)-2-[(3-R-2-oxo-2H [1,2,4]triazino[2,3-c]quinazoline-6-yl)thio]acetamides synthesis by aminolysis of activated by thionyl chloride or carbonyldiimidazole [(3-R-2-oxo-2H [1,2,4]triazino[2,3-c]quinazolin-6-yl)-thio]acetic acids and alkylation of the 3 R-6-thio-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazoline-2-ones potassium salts with N-cycloalkyl-(cycloalkylaryl)-2-chloroacetamides are proposed. The structures of compounds are determined by (1)H, (13)C NMR, LC-MS and EI-MS analysis. The in vitro anticancer, antibacterial activity and Photobacterium leiognathi Sh1 bioluminescence inhibition of synthesized compounds were revealed. SAR results were discussed. Compound 4.10 was found to be the most anticancer active one, selectively influenced on the non-small cell lung and CNS cancer cell lines, especially on the HOP-92 (log GI(50) = -6.01) and U251 (log GI(50) = 6.00). PMID- 22051066 TI - Comparative studies on interactions of baicalein, baicalin and scutellarin with lysozyme. AB - The interactions of baicalein, baicalin and scutellarin with lysozyme (LYSO) were studied by fluorescence and UV spectroscopy. The results showed that all the three flavones can quench the fluorescence of LYSO via static quenching with the distance between the donor and acceptor less than 7 nm. The hydroxyl at B-ring gave flavones an advantage to binding with LYSO. Electrostatic forces played a major role in stabilizing baicalein-LYSO complex and baicalin-LYSO complex, whereas hydrophobic interactions in scutellarin-LYSO. Furthermore, the presence of pantothenic acid can increase the binding constant and the number of binding sites between flavones and LYSO. PMID- 22051067 TI - Surgical strategy for aortic coarctation repair resulting in physiologic arm and leg blood pressures. AB - OBJECTIVE: The goal of aortic coarctation repair is laminar aortic blood flow resulting in a negative or absent arm:leg blood pressure (BP) gradient. Despite satisfactory relief of coarctation, associated arch hypoplasia can result in residual obstruction and postoperative upper body hypertension. INTERVENTION: We devised a surgical strategy to create a tension-free anastomosis with a diameter as large as both the adjacent proximal and distal aorta using a radically extended end-to-end anastomosis via sternotomy and/or thoracotomy. Sternotomy is chosen when there is significant transverse arch hypoplasia defined as a distal transverse arch <= diameter of the left carotid artery, presence of a common brachiocephalic trunk, or coexisting intracardiac lesion requiring repair. Thoracotomy is used in all other cases. RESULTS: From 2000 to 2008, 95 consecutive patients were repaired using this approach, 35 with sternotomy and 60 with thoracotomy. At a mean follow-up of 50 +/- 23 months, mean systolic BP was 94 +/- 10 mm Hg, and 84% of patients had no residual arm:leg BP gradient. Mean arm:leg BP gradient was not statistically different between groups (-8.5 +/- 15 sternotomy and -7.0 +/- 10 mm Hg thoracotomy, P= .7). With Doppler echocardiography, 96% of patients demonstrated normal early diastolic reversal of blood flow in the descending thoracic aorta. CONCLUSIONS: For aortic coarctation repair in infancy, a strategy designed to directly address aortic arch hypoplasia results in excellent intermediate-term results with normal BP, physiologic arm:leg BP relationship, and near normal descending aortic blood flow velocities by Doppler. PMID- 22051069 TI - Modeling the Calvin-Benson cycle. AB - BACKGROUND: Modeling the Calvin-Benson cycle has a history in the field of theoretical biology. Anyone who intends to model this system will look at existing models to adapt, refine and improve them. With the goal to study the regulation of carbon metabolism, we investigated a broad range of relevant models for their suitability to provide the basis for further modeling efforts. Beyond a critical analysis of existing models, we furthermore investigated the question how adjacent metabolic pathways, for instance photorespiration, can be integrated in such models. RESULTS: Our analysis reveals serious problems with a range of models that are publicly available and widely used. The problems include the irreproducibility of the published results or significant differences between the equations in the published description of the model and model itself in the supplementary material. In addition to and based on the discussion of existing models, we furthermore analyzed approaches in PGA sink implementation and confirmed a weak relationship between the level of its regulation and efficiency of PGA export, in contrast to significant changes in the content of metabolic pool within the Calvin-Benson cycle. CONCLUSIONS: In our study we show that the existing models that have been investigated are not suitable for reuse without substantial modifications. We furthermore show that the minor adjacent pathways of the carbon metabolism, neglected in all kinetic models of Calvin-Benson cycle, cannot be substituted without consequences in the mass production dynamics. We further show that photorespiration or at least its first step (O2 fixation) has to be implemented in the model if this model is aimed for analyses out of the steady state. PMID- 22051068 TI - Polymorphisms of the endothelial nitric oxide synthase (NOS3) gene in preeclampsia: a candidate-gene association study. AB - BACKGROUND: The endothelial nitric oxide synthase gene (NOS3) has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the NOS3 gene in a population of Caucasian origin. METHODS: We examined the association of three common variants of the NOS3 gene (4b/a, T-786C and G894T) and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the NOS3 variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between NOS3 polymorphisms and preeclampsia. RESULTS: The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association. CONCLUSIONS: Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common NOS3 variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further. PMID- 22051070 TI - General guidelines for detection of anthelmintic resistance in horses. Preface. PMID- 22051071 TI - Phylogenetic and host-parasite relationship analysis of Henneguya multiplasmodialis n. sp. infecting Pseudoplatystoma spp. in Brazilian Pantanal wetland. AB - A new species of the genus Henneguya (Henneguya multiplasmodialis n. sp.) was found infecting the gills of three of 89 specimens (3.3%) of Pseudoplatystoma corruscans and two of 79 specimens (2.6%) of Pseudoplatystoma reticulatum from rivers in the Pantanal wetland, Brazil. Partial sequencing of the 18S rDNA gene of the spores obtained from one plasmodium from the gills of P. corruscans and other one from the gills of P. reticulatum, respectively, resulted in a total of 1560 and 1147 base pairs. As the spores of H. multiplasmodialis n. sp. resemble those of Henneguya corruscans, which is also a parasite of P. corruscans, sequencing of the 18S rDNA gene of the spores of H. corruscans found on P. corruscans caught in the Brazilian Pantanal wetland was also provided to avoid any taxonomic pendency between these two species, resulting in 1913 base pairs. The sequences of H. multiplasmodialis n. sp. parasite of P. corruscans and P. reticulatum and H. corruscans did not match any of the Myxozoa available in the GenBank. The similarity of H. multiplasmodialis n. sp. obtained from P. corruscans to that from P. reticulatum was of 99.7%. Phylogeny revealed a strong tendency among Henneguya species to form clades based on the order and/or family of the host fish. H. multiplasmodialis n. sp. clustered in a clade with Henneguya eirasi and H. corruscans, which are also parasites of siluriforms of the family Pimelodidae and, together with the clade composed of Henneguya spp. parasites of siluriforms of the family Ictaluridae, formed a monophyletic clade of parasites of siluriform hosts. The histological study revealed that the wall of the plasmodia of H. multiplasmodialis n. sp. were covered with a stratified epithelium rich in club cells and supported by a layer of connective tissue. The interior of the plasmodia had a network of septa that divided the plasmodia into numerous compartments. The septa were composed of connective tissue also covered on both sides with a stratified epithelium rich in club cells. Inflammatory infiltrate was found in the tissue surrounding the plasmodia as well as in the septa. PMID- 22051072 TI - Detection of specific antibodies in dogs infected with Angiostrongylus vasorum. AB - Canine angiostrongylosis, caused by the nematode Angiostrongylus vasorum, is an emerging cardiopulmonary disease in Europe which can be fatal if left untreated. We determined the diagnostic value of the specific detection of antibodies against A. vasorum adult somatic antigen, adult excretory/secretory (E/S) antigen and first stage larvae (L1) somatic antigen in ELISAs. Also, A. vasorum adult somatic antigen purified by monoclonal antibodies (mAb) was evaluated in a sandwich-ELISA. Among the crude antigens, the best sensitivities when testing 21 naturally infected dogs were obtained using adult E/S and somatic antigen (85.7% and 76.2%, respectively), which were comparable with the results of the sandwich ELISA based on mAb-purified antigens (81%). The ELISA performed with L1 antigen had the lowest sensitivity (42.9%). In experimentally inoculated dogs, the sensitivities ranged from 97.7% to 100% with all test settings. The specificity was 98.8% (92.5-99.9%, 95% CI) with all ELISAs using sera of 82 randomly selected dogs. Cross-reactions using adult somatic, adult E/S and L1 somatic antigen were observed in sera of dogs infected with Crenosoma vulpis, Dirofilaria immitis, Dirofilaria repens, and Eucoleus aerophilus. In contrast, using the mAb-purified antigens, the cross-reactions were minimal. Depending on the antigens used, specific antibodies were detected starting between 13 and 21 days post experimental inoculation (dpi), and at latest between 35 and 48 dpi, thus before or around the onset of patency. The serological follow-up of four A. vasorum infected dogs after anthelmintic treatment at 88 dpi showed a decrease of antibody levels after drug administration, and the animals became seronegative 2 9 weeks later. Two untreated dogs remained seropositive. In four dogs treated 4 dpi, virtually no antibody-reaction was detectable, with the exception of the ELISA performed with L1 antigen. The early detection of specific antibodies against A. vasorum by ELISA represents a valid alternative for a reliable diagnosis and for follow-up investigations after anthelmintic treatment. PMID- 22051073 TI - Comparison of loop-mediated isothermal amplification (LAMP) and real-time PCR method targeting a 529-bp repeat element for diagnosis of toxoplasmosis. AB - Loop-mediated isothermal amplification (LAMP) is a simple method that can amplify DNA with high specificity, sensitivity, and rapidity. In this study, we compared the performance of LAMP and real-time PCR assays for diagnosis of toxoplasmosis. We designed a real-time PCR assay targeting a 529 bp element repeated 200-300 times in the Toxoplasma gondii genome. The detection limits of the LAMP and real time PCR assays were 10 fg/MUL and 1 fg/MUL of T. gondii DNA, respectively. Conventional PCR, LAMP, and real-time PCR methods were applied to detect T. gondii DNA in blood samples from 284 pigs and 292 sheep. Positive results were obtained with 0.4%, 3.2%, and 4.2% of the pig samples and 3.8%, 17.1%, and 17.8% of the sheep samples with conventional PCR, LAMP, and real-time PCR analyses, respectively. The real-time PCR assay provided the most sensitive diagnosis of toxoplasmosis, but the LAMP assay has potential as an alternative tool for detection of T. gondii in the field. PMID- 22051074 TI - Estrogen receptor alpha gene variants and major depressive episodes. AB - BACKGROUND: Despite evidence of estrogen's mood-enhancing effects, the association between estrogen receptor (ER) gene variants and lifetime major depression has been insufficiently studied. METHODS: 3987 community-dwelling women aged 65years and over were recruited in France as part of the Three City Study. Current and past major depressive disorders (MDD) were diagnosed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. The association between two common estrogen receptor alpha (ESR1) polymorphisms with lifetime MDD was examined using adjusted logistic regression models, taking into account the age at first depressive episode and the recurrence of depression. RESULTS: Women homozygous for the variant G allele of ESR1 rs9340799 had a 1.6 fold increased risk of MDD across their lifetime compared with women who were homozygous for the A allele (p=0.009). There was a similar non-significant trend for the C allele of rs2234693 being associated with an increased risk (p=0.09). Polytomous regression analysis further indicated that the GG genotype of rs9340799 was specifically associated with an increased risk of recurrent depressive episodes, regardless of the age at first onset of depression relative to the menopause. LIMITATIONS: The duration and severity of depressive episodes was not considered in the analysis. CONCLUSIONS: This is the first study to examine the association between ESR1 gene variants and lifetime MDD. Our findings indicate a significant association between common variants and the risk of recurrent depressive episodes. This suggests that certain depressed women could be most responsive to hormone-based treatment. PMID- 22051075 TI - Subthreshold symptoms in bipolar disorder: impact on neurocognition, quality of life and disability. AB - OBJECTIVE: To provide empirical evidence of the effect of subthreshold symptomatology (both depressive and manic) on psychosocial functioning, neurocognition and quality of life in bipolar disorder. METHODS: A total of 133 participants were enrolled for this study (bipolar patients, n=103; healthy controls, n=30). Patients were divided into two groups according to their levels of subthreshold symptomatology: the subsyndromic group was constituted by those patients with upper levels of subthreshold symptomatology (HDRS>=4 and YMRS>=3) and the asymptomatic group represented the patients with lower scores (HDRS<=3 and YMRS<=2). All participants were administered a comprehensive neuropsychological battery. Moreover the patients answered the SF-36 (Quality of Life, QoL) and were interviewed with the WHODAS-2 (Psychosocial functioning and disability). One-way ANOVA were used in order to compare the differences between the three groups. RESULTS: The analyses revealed that both patients groups, albeit free of acute symptoms of mania or depression, differed in terms of functioning and disability assessed with the WHODAS-2. Specifically, the total global score of disability was higher for the subsyndromic group indicating more impairment (p=0.008). The same pattern of impairment was found for three of its domains: "understanding and communicating" (p=0.013); "self-care" (p=0.035) and "getting along with others" (p=0.024). The subsyndromic group also scored lower when compared to their counterparts in the Mental Component of QoL of the SF-36 (p=0.045). Finally, in the neuropsychological performance verbal learning and memory was found to be impaired regardless the levels of subthreshold symptomatology, suggesting that this variable is a robust indicator of neuropsychological impairment in BD patients. CONCLUSIONS: This report presents empirical data suggesting a moderate impact of subthreshold symptoms on functioning/disability and QoL and a discrete impact on neuropsychological impairment. PMID- 22051076 TI - Compulsive buying in bipolar disorder: is it a comorbidity or a complication? AB - BACKGROUND: The objective of this study was to investigate the frequency of compulsive buying in bipolar disorder (BD), to compare it with healthy controls, and to search if there is a difference between bipolar cases with and without compulsive buying in terms of sociodemographic qualities, temperament, clinical characteristics and comorbid diagnoses. METHODS: One-hundred outpatient cases diagnosed as BD according to DSM-IV were evaluated consecutively. Following the diagnosis interview (SCID-I and II) the subjects completed the mood disorders registry form, Compulsive Buying Scale and TEMPS-A. RESULTS: Compulsive buying scores were higher in bipolar patients than healthy controls (p<0.001). Cases with compulsive buying revealed higher cyclothymic and irritable temperament scores than other bipolar patients (p=0.029 vs 0.045). Premenstrual syndrome and postpartum onset were more frequent, while psychotic symptoms were less in compulsive buyer bipolar patients (p=0.002, 0.009 vs 0.034). Severity of episode was lower (p=0.01), number of episodes was higher (p=0.009). Acute onset and remission before and after maintenance treatment were more frequent in patients with compulsive buying (p=0.011 and p=0.011). Full remission between episodes was 100%. Cases with axis-1 and axis-2 comorbidities demonstrated higher compulsive buying scores (p=0.025 and 0.005). LIMITATIONS: Treatment regimen differences between patients are a limitation of the study. CONCLUSIONS: This is the first study to relate compulsive buying with the clinical characteristics of BD. Our results reveal that compulsive buying in BD occurs together with mood episodes which are not very severe, but frequent and with abrupt onset. PMID- 22051077 TI - Histopathologic features of canine distichiasis. AB - OBJECTIVE: To describe the histologic features of canine distichiasis using excised tarsoconjunctival specimens that included roots of distichiatic cilia. PROCEDURES: The study group included 21 strips of cilia-bearing tarsoconjunctiva resected from 20 dogs with distichiasis. Eyelid tissue specimens were also collected from 11 euthanized dogs without distichiasis to serve as controls. All flat mount preparations were processed for histologic examination, and serial sections were stained with hematoxylin-eosin (H&E). A total of 157 slides were examined for the study group to describe the follicles and path of the distichiatic hairs and determine their potential connection with the tarsal glands. A total of 82 slides were examined for the control group. RESULTS: In 19 of the 20 dogs with distichiasis, serial sections of the specimens identified anatomic segments of hair follicles located abnormally in the eyelid tarsus and associated with the aberrant cilia. They appeared as hair bulbs adjacent to tarsal glands, middle portions of hair follicles located between sebaceous lobules, and single or multiple hair shafts present within the sebaceous duct. The tarsal glands in the cilia-bearing tarsoconjunctiva were not different from those of the controls, in which no distichiatic hair bulbs or shafts were observed. CONCLUSIONS: These results demonstrate that adventitious cilia are not associated with histologic changes of the tarsal glands, and appear to arise from ectopic hair follicles present in the tarsus. Canine distichiasis may result from anomalous regulation of morphogenesis of hair follicles in the mesenchymal tissue of the tarsal plate. PMID- 22051078 TI - Peptide therapeutics for CNS indications. AB - Neuropeptides play a crucial role in the normal function of the central nervous system and peptide receptors hold great promise as therapeutic targets for the treatment of several CNS disorders. In general, the development of peptide therapeutics has been limited by the lack of drug-like properties of peptides and this has made it very difficult to transform them into marketable therapeutic molecules. Some of these challenges include poor in vivo stability, poor solubility, incompatibility with oral administration, shelf stability, cost of manufacture. Recent technical advances have overcome many of these limitations and have led to rapid growth in the development of peptides for a wide range of therapeutic indications such as diabetes, cancer and pain. This review examines the therapeutic potential of peptide agonists for the treatment of major CNS disorders such as schizophrenia, anxiety, depression and autism. Both clinical and preclinical data has been accumulated supporting the potential utility of agonists at central neurotensin, cholecystokinin, neuropeptide Y and oxytocin receptors. Some of the successful approaches that have been developed to increase the stability and longevity of peptides in vivo and improve their delivery are also described and potential strategies for overcoming the major challenge that is unique to CNS therapeutics, penetration of the blood-brain barrier, are discussed. PMID- 22051079 TI - The liver X receptor modulator 22(S)-hydroxycholesterol exerts cell-type specific effects on lipid and glucose metabolism. AB - The aim of this study was to explore the effects of 22(S)-hydroxycholesterol (22(S)-HC) on lipid and glucose metabolism in human-derived cells from metabolic active tissues. Docking of T0901317 and 22(S)-HC showed that both substances fitted into the ligand binding domain of liver X receptors (LXR). Results show that while several lipogenic genes were induced by T0901317 in myotubes, HepG2 cells and SGBS cells, effect of 22(S)-HC varied more between cell types. In myotubes, most lipogenic genes were downregulated or unchanged by 22(S)-HC, whereas a more diverse pattern was found in HepG2 and SGBS cells. Treatment with 22(S)-HC induced sterol regulatory element binding transcription factor 1 in SGBS and HepG2 cells, but not in myotubes. Fatty acid synthase was downregulated by 22(S)-HC in myotubes, upregulated in SGBS and unchanged in HepG2 cells. De novo lipogenesis was increased by T0901317 in all cell models, whereas differently affected by 22(S)-HC depending on the cell type; decreased in myotubes and HepG2 cells, whereas increased in SGBS cells. Oxidation of linoleic acid was reduced by 22(S)-HC in all cell models while glucose uptake increased and tended to increase in myotubes and SGBS cells, respectively. Cholesterol efflux was unaffected by 22(S)-HC treatment. These results show that 22(S)-HC affects LXR-regulated processes differently in various cell types. Ability of 22(S)-HC to reduce lipogenesis and lipid accumulation in myotubes and hepatocytes indicate that 22(S)-HC might reduce lipid accumulation in non-adipose tissues, suggesting a potential role for 22(S)-HC or a similar LXR modulator in the treatment of type 2 diabetes. PMID- 22051080 TI - Ex vivo spontaneous generation of 19-norandrostenedione and nandrolone detected in equine plasma and urine. AB - 19-Norandrostenedione (NAED) and nandrolone are anabolic-androgenic steroids (AASs). Nandrolone was regarded solely as a synthetic AAS until the 1980s when trace concentrations of apparently endogenous nandrolone were detected in urine samples obtained from intact male horses (stallions). Since then, its endogenous origin has been reported in boars and bulls; endogenous NAED and nandrolone have been identified in plasma and urine samples collected from stallions. More recently, however, it was suggested that NAED and nandrolone detected in urine samples from stallions are primarily artifacts due to the analytical procedure. The present study was undertaken to determine whether NAED and nandrolone detected in plasma and urine samples collected from stallions are truly endogenous or artifacts from sample processing. To answer this question, fresh plasma and urine samples from >=8 stallions were analyzed for the two AASs, soon after collection, by liquid chromatography hyphenated to tandem mass spectrometry (LC-MS/MS). NAED and nandrolone were not detected in fresh plasma samples but detected in the same samples post storage. Concentrations of both AASs increased with storage time, and the increases were greater at a higher storage temperature (37 degrees C versus 4 degrees C, and ambient temperature versus 4 degrees C). Although NAED was detected in some fresh stallion urine samples, its concentration (<407 pg/mL) was far lower (<0.4%) than that in the same samples post storage (at ambient temperature for 15 days). Nandrolone was not detected in most of fresh urine samples but detected in the same samples post storage. Based on these results, it is concluded that all NAED and nandrolone detected in stored plasma samples of stallions and most of them in the stored urine samples are not from endogenous origins but spontaneously generated during sample storage, most likely from spontaneous decarboxylation of androstenedione-19-oic acid and testosterone-19-oic acid. To our knowledge, it is the first time that all NAED and nandrolone detected in plasma of stallions and most of them detected in the urine have been shown to be spontaneously generated in vitro during sample storage. This finding would have significant implications with regard to the regulation of the two steroids in horse racing. PMID- 22051081 TI - The changing face of informed surgical consent. AB - OBJECTIVES: To determine whether procedure-specific brochures improve patients' pre-operative knowledge, to determine the amount of information expected by patients during the consenting process, and to determine whether the recently proposed 'Request for Treatment' consenting process is viable on a large scale. METHOD: A prospective, questionnaire-based study of 100 patients admitted for selected, elective surgical procedures. RESULTS: In total, 99 per cent of patients were satisfied with the information received in the out-patient department, regarding the proposed procedure. However, 38 per cent were unable to correctly state the nature of the surgery or specific procedure they were scheduled to undergo. Although the vast majority of patients were able to state the intended benefits to be gained from the procedure, only 54 per cent were able to list at least one potential complication, and 80 per cent indicated that they wished to be informed about all potential complications, even if these occurred in less than 1 per cent of cases. CONCLUSIONS: The introduction of procedure specific brochures improved patients' pre-operative knowledge. Although the failings of current consenting practice are clear, the Request for Treatment consenting process would not appear to be a viable alternative because of the large number of patients unable to accurately recall the nature of the proposed surgery or potential complications, following consent counselling. PMID- 22051082 TI - Comment on: Does bariatric surgery reduce the risk of major cardiovascular events? A retrospective cohort study of morbidly obese surgical patients. PMID- 22051083 TI - Influence of white mineral trioxide aggregate on inflammatory cells before and after expiry date. AB - INTRODUCTION: The aim of this study was to compare the effect of subcutaneously implanted white mineral trioxide aggregate (WMTA) on inflammatory reactions before and after expiry date. METHODS: Fifty Wistar rats were used in this study. Polyethylene tubes were filled with WMTA with expiry dates of 2008, 2009, and 2011, and empty ones serving as the controls were implanted into the subcutaneous tissue. The rats were sacrificed at 7-, 14-, 28-, and 60-day intervals. 5-MUm sections were stained with hematoxylin and eosin and observed under a light microscope. Inflammatory reactions were categorized as 0, none (without inflammatory cells); 1, mild (inflammatory cells < 25); 2, moderate (25-125 inflammatory cells); and 3, severe (more than 125 inflammatory cells). Statistical analysis was performed with Kruskal-Wallis test. RESULTS: All the experimental materials provoked moderate to severe inflammatory reactions after 7 days, which significantly differed from the control group (P < 0.05). At 14-day interval, WMTA with expiry date of 2008 and the control group elicited mild to moderate infiltration of inflammatory cells. However, WMTA with expiry dates of 2009 and 2011 provoked moderate to severe inflammatory reactions, which were significantly different from WMTA with expiry date of 2008 and the control group (P < 0.05). At 28- and 60-day intervals, the overall inflammation subsided in all the groups to mild to moderate infiltration of inflammatory cells without any significant differences (P < 0.05). CONCLUSION: It seems that the expiry date has less negative effects on the response of inflammatory cells. WMTA keeps its biocompatibility even after expiry date. PMID- 22051084 TI - Prediction of visceral response to multi-directional loading as measured by the chestband. AB - Thoracic and abdominal injury outcomes are correlated to chestband-derived uniaxial metrics in post-mortem human specimen (PMHS) experiments. Yet, uniaxial metrics may neglect deformations remote from the measurement site which still may be relevant to injury risk in motor vehicle crashes. Using 2D chestband contours from PMHS experiments, visceral strain and strain energy density responses were examined using a planar viscoelastic finite element model. The model was exercised by applying to the periphery 21 subject-specific PMHS chestband deformation patterns representing four boundary conditions: (a) lateral impact with close-proximity torso airbag, (b) stationary close-proximity torso airbag loading, (c) flat rigid lateral impact, and (d) antero-lateral oblique rigid impact. ANOVA determined that mean peak responses were dependent on boundary condition (p<0.002). Using matched-pair experiment injury outcomes, 50% risk of visceral trauma corresponded to localized strain and strain energy density of 1.55 and 33.0 kJ/m(3) (p<0.1). Although strains were large, model response demonstrated sensitivity to impact boundary conditions and observed PMHS trauma. This model formulation is useful for comparative examination of injury risk from torso deformations measured experimentally using the chestband device. PMID- 22051085 TI - Exoskeleton robots for upper-limb rehabilitation: state of the art and future prospects. AB - Current health services are struggling to provide optimal rehabilitation therapy to victims of stroke. This has motivated researchers to explore the use of robotic devices to provide rehabilitation therapy for strokepatients. This paper reviews the recent progress of upper limb exoskeleton robots for rehabilitation treatment of patients with neuromuscular disorders. Firstly, a brief introduction to rehabilitation robots will be given along with examples of existing commercial devices. The advancements in upper limb exoskeleton technology and the fundamental challenges in developing these devices are described. Potential areas for future research are discussed. PMID- 22051086 TI - Matrix effects in the energy dispersive X-ray analysis of CaO-Al(2)O(3)-MgO inclusions in steel. AB - Energy dispersive X-ray microanalysis of micron-sized inclusions in steel is of considerable industrial importance. Measured spectra and Monte Carlo simulations show a significant effect of the steel matrix on analysis of CaO-Al(2)O(3)-MgO inclusions: the steel matrix filters the softer (Al and Mg) characteristic X rays, increasing the relative height of the Ca peak. Bulk matrix correction methods would not result in correct inclusion compositions, but operating at a lower acceleration voltage shifts the effect to smaller inclusion sizes. PMID- 22051087 TI - Uncertainty studies of topographical measurements on steel surface corrosion by 3D scanning electron microscopy. AB - Pitting corrosion is a damage mechanism quite serious and dangerous in both carbon steel boiler tubes for power plants which are vital to most industries and stainless steels for orthopedic human implants whose demand, due to the increase of life expectation and rate of traffic accidents, has sharply increased. Reliable methods to characterize this kind of damage are becoming increasingly necessary, when trying to evaluate the advance of damage and to establish the best procedures for component inspection in order to determine remaining lives and failure mitigation. A study about the uncertainties on the topographies of corrosion pits from 3D SEM images, obtained at low magnifications (where errors are greater) and different stage tilt angles were carried out using an in-house software previously developed. Additionally, measurements of pit depths on biomaterial surfaces, subjected to two different surface treatments on stainless steels, were carried out. The different depth distributions observed were in agreement with electrochemical measurements. PMID- 22051088 TI - Elasticity and nanomechanical response of Aspergillus niger spores using atomic force microscopy. AB - The elasticity and nanomechanical response of Aspergillus niger spores determined using atomic force microscopy (AFM) and nanoindentation are discussed. The force displacement curve of the spore surfaces shows that the average surface roughness of spores was approximately 33 nm and that the adhesion force ranged from 9 to 28 nN. The Young's modulus of the A. niger spores ranged from 0.1 to 21.4 GPa and the hardness ranged from 0.01 to 0.17 GPa. The critical buckling load of the spore membrane is 290 MUN. PMID- 22051089 TI - Associations of obesity genes with obesity-related outcomes in multiethnic children. AB - BACKGROUND AND AIMS: Genome-wide association studies (GWAS) have identified several loci that are associated with body mass index (BMI = kg/m(2)). However, little is known regarding whether the genetic basis of BMI differs among children of diverse racial/ethnic backgrounds, how the cumulative effect of these genes influences weight, or the contribution of these variants to body composition. This study examined the association between 17 GWAS-identified loci located in 16 genes and body-composition phenotypes in a multiethnic pediatric sample and evaluated the association of a composite genetic risk score with these phenotypes. METHODS: Anthropometric measures of BMI, waist circumference and waist-to-hip ratio were obtained in a sample of 298 children. Lean and fat mass were obtained from dual-energy X-ray absorptiometry (DXA). Genotypes of 17 single nucleotide polymorphisms (SNPs) were tested for association with the phenotypic measures, adjusted by standard covariates and estimates of genetic admixture. RESULTS: Both SNPs rs8050136 and rs9939609 in FTO were associated with BMI and waist circumference in a direction opposite to that observed among adults, and an inverse association was detected between the risk variant in MC4R and total lean body mass. Lean body mass mediated the association between TMEM18 and BMI. The association between the genetic risk score and body composition differed according to ethnic/racial classification. CONCLUSIONS: Our findings suggest that genetic associations with BMI among children are different from those in adults, that some loci may operate through lean body mass, and that genetic risk scores will not have universal applicability across ethnic/racial groups. PMID- 22051091 TI - Going on a drug holiday? PMID- 22051092 TI - Low bone mass prevalence, therapy type, and clinical risk factors in an HIV infected Brazilian population. AB - Low bone mineral density (BMD) has been described in human immunodeficiency virus (HIV)-infected patients, but data on associated factors are still unclear, and to our knowledge, no reports are available in Brazil. Our goal was to evaluate BMD in HIV patients attending an outpatient clinic in Vitoria, Brazil. A sectional study was performed in 300 HIV-infected patients to measure BMD by dual-energy X ray absorptiometry (DXA). Age, gender, anthropometric parameters, nadir and current CD4 cell count, HIV viral load, smoking habit, and current antiretroviral therapy (ART) associations were investigated by multivariable analysis. Based on World Health Organization T-score ranges, low BMD (T-score <-1.0 standard deviation [SD] in postmenopausal women and men aged 50 and older or Z-score <- 2.0 SD in premenopausal women and men below the age of 50) was detected in 54.7% (95% confidence interval: 49.1-60.3%) of the 300 enrolled patients. The observed median age was 46 yr (interquartile range: 39-52), 58% were male, 88.5% were on ART, and 21.4% smoked. The following factors were identified, by multiple logistic modeling, as being independently associated with low BMD: (1) male gender (4.6 [1.28-16.39]), (2) body mass index lower than 25 kg/m(2) (2.9 [1.31 6.49]), (3) menopause (13.4 [2.53-71.12]), and (4) HIV-1 undetectable viral load (7.9 [1.96-32.25]). Conversely, zidovudine (0.2 [0.04-0.85]) and nevirapine (0.1 [0.02-0.38]) use were inversely associated with low BMD. Low BMD was frequently found in our cohort of about 300 Brazilian HIV-infected subjects. This study supports the need for periodic DXA testing in HIV outpatient clinics. PMID- 22051093 TI - Shorter sleep may be a risk factor for impaired bone mass accrual in childhood. AB - The purpose of the study was to investigate whether sleep duration during early childhood was associated with fat mass and bone mineral content (BMC). BMC and fat mass were measured by dual-energy X-ray absorptiometry in children (n=336) aged 4-12 yr. Sleep was quantified according to parental report of hours slept at night and napping. The relationship between sleep pattern and body composition was tested using analysis of variance including confounding factors. Based on the sample distribution, children were grouped into tertiles of sleep duration. BMC was greater in children with longer sleep duration (p=0.02). Age was inversely associated with sleep duration; therefore, the sample was analyzed by age category using age 7 yr as a cut-off point. The relationship remained significant only among younger children. Napping was positively associated with BMC (p=0.001). Sleep duration was not associated with fat parameters. Longer sleep duration may allow for optimal energy resource partitioning in which bone is favored. Sleep duration of less than 8h may impair bone mass accrual, particularly during periods of rapid growth. PMID- 22051094 TI - Discriminative ability of heel quantitative ultrasound in postmenopausal women with prevalent low-trauma fractures: application of optimal threshold cutoff values using CART models. AB - Quantitative ultrasound (QUS) of the heel has been proposed as a screening tool to evaluate the bone status and risk of osteoporotic fragility fractures. The aim of this study was to define threshold values of QUS that would maximize the predictive ability of this technique to discriminate subjects with fragility fractures. A cross-sectional analysis was made of a cohort of 1132 postmenopausal women with a mean age of 58 yr. A total of 361 women (31.9%) presented with a history of osteoporotic fracture. Most fractures (74.1%) were nonvertebral. For all patients, a questionnaire of osteoporosis risk factors and measurements of the heel QUS and bone mineral density at the lumbar spine and the proximal femur obtained by dual-energy X-ray absorptiometry (DXA) were assessed. Spinal radiographs were assessed for fractures and historical nonvertebral fragility fractures. Sensitivity, specificity, predictive values, likelihood ratios, and receiver operator characteristic (ROC) curve QUS values were calculated using the optimal threshold identified in the classification and regression trees (CART) models. Cutoff values calculated from the best CART model (i.e., a quantitative ultrasound index (QUI) greater than 88.5% in women aged 58 yr or older) yielded 88.8% (95% confidence interval [CI]: 81.4-93.5) for sensitivity, a negative predictive value of 93.8 (95% CI: 89.4-96.4), and 70.4% (95% CI: 64.6-75.7) for specificity. This cutoff value would obviate the need to perform DXA in 43.1% of the population. The area under the ROC curve of the best model was 0.8363 (95% CI: 0.8249-0.8477). In conclusion, QUS was shown to discriminate between women with and without a history of fragility fracture and constitutes a useful tool for assessing fracture risk. The application of decision trees (CART analyses) was helpful to define the optimal threshold QUS values. PMID- 22051095 TI - Lanthanum carbonate interference with lumbar spine DXA. PMID- 22051097 TI - Applying stable isotopes to examine food-web structure: an overview of analytical tools. AB - Stable isotope analysis has emerged as one of the primary means for examining the structure and dynamics of food webs, and numerous analytical approaches are now commonly used in the field. Techniques range from simple, qualitative inferences based on the isotopic niche, to Bayesian mixing models that can be used to characterize food-web structure at multiple hierarchical levels. We provide a comprehensive review of these techniques, and thus a single reference source to help identify the most useful approaches to apply to a given data set. We structure the review around four general questions: (1) what is the trophic position of an organism in a food web?; (2) which resource pools support consumers?; (3) what additional information does relative position of consumers in isotopic space reveal about food-web structure?; and (4) what is the degree of trophic variability at the intrapopulation level? For each general question, we detail different approaches that have been applied, discussing the strengths and weaknesses of each. We conclude with a set of suggestions that transcend individual analytical approaches, and provide guidance for future applications in the field. PMID- 22051098 TI - Corneal sensitivity in healthy, immature, and adult alpacas. AB - OBJECTIVE: To determine the corneal sensitivity of healthy, immature, and adult alpacas to establish normal reference values for this species. ANIMALS STUDIED: Six normal crias and 18 normal adult alpacas. PROCEDURES: Corneal sensitivity was determined by evaluating the corneal touch threshold (CTT) in five regions of the cornea using a Cochet-Bonnet aesthesiometer. The nylon filament length in cm was then converted to applied pressure values in mg/0.0113 mm(2) and g/mm(2) using a conversion chart. RESULTS: The central region of the cornea was the most sensitive, and the dorsal and temporal regions were the least sensitive in alpacas. There were no significant differences between the right and left eyes or between values in males and females at any site. Crias had significantly greater corneal sensitivity compared with adult alpacas in all five regions of the cornea that were evaluated. CONCLUSIONS: Normal reference values for CTT in alpacas were established using a Cochet-Bonnet aesthesiometer. The central region of the cornea is the most sensitive in alpacas, and crias have higher corneal sensitivity than adult alpacas. PMID- 22051096 TI - The role of GLP-1 mimetics and basal insulin analogues in type 2 diabetes mellitus: guidance from studies of liraglutide. AB - In people with type 2 diabetes mellitus (T2DM), the incretin effect is reduced, but the recent advent of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide (GLP)-1 agonists/analogues has enabled restoration of at least some of the function of the incretin system, with accompanying improvements in glycaemic control. Two GLP-1 receptor agonists/analogues are currently approved for the treatment of T2DM-exenatide (Byetta(r), Eli Lilly & Co., Indianapolis, IN, US) and liraglutide (Victoza(r), Novo Nordisk, Bagsvaerd, Denmark); a once-weekly formulation of exenatide (Bydureon(r), Eli Lilly & Co.) has also been approved by the European Medicines Agency. The National Institute for Health and Clinical Excellence (NICE) has recently published guidance on the use of liraglutide in T2DM, based on evidence from the Liraglutide Effect and Action in Diabetes (LEAD) Phase III trial programme, which compared liraglutide with existing glucose lowering therapies, such as exenatide and insulin glargine. The LEAD programme reported HbA1c reductions from 0.8 to 1.5% with liraglutide (1.2 and 1.8 mg), accompanied by low rates of hypoglycaemia and some weight loss; side effects were primarily gastrointestinal in nature (e.g. nausea and diarrhoea). Based on the findings of the LEAD studies and the NICE recommendation, liraglutide now represents an important therapy widely available in the UK for certain patient groups, including those with a body mass index (BMI) >=35.0 kg/m(2) , and patients with a BMI <35 kg/m(2) who are considered unsuitable for insulin and are failing to meet targets for glycaemic control with oral agents. NICE guidelines still suggest that most patients without considerable obesity (BMI <35 kg/m(2) ) are probably best managed using insulin therapy. Evidence also suggests a future role for GLP-1 mimetics in combination with basal insulin. PMID- 22051099 TI - Variation in the CXCR1 gene (IL8RA) is not associated with susceptibility to chronic periodontitis. AB - BACKGROUND: The chemokine receptor 1 CXCR-1 (or IL8R-alpha) is a specific receptor for the interleukin 8 (IL-8), which is chemoattractant for neutrophils and has an important role in the inflammatory response. The polymorphism rs2234671 at position Ex2+860G>C of the CXCR1 gene causes a conservative amino acid substitution (S276T). This single nucleotide polymorphism (SNP) seemed to be functional as it was associated with decreased lung cancer risk. Previous studies of our group found association of haplotypes in the IL8 and in the CXCR2 genes with the multifactorial disease chronic periodontitis. In this study we investigated the polymorphism rs2234671 in 395 Brazilian subjects with and without chronic periodontitis. FINDINGS: Similar distribution of the allelic and genotypic frequencies were observed between the groups (p>0.05). CONCLUSIONS: The polymorphism rs2234671 in the CXCR1 gene was not associated with the susceptibility to chronic periodontitis in the studied Brazilian population. PMID- 22051100 TI - Supporting the midwifery practice-based curriculum: the role of the link lecturer. AB - BACKGROUND: It is essential that Approved Education Institutions (AEIs) support practice learning to the education standards required by the Nursing and Midwifery Council (NMC, 2009). Evaluating whether midwife lecturers bring a unique contribution to the outcomes of preregistration midwifery education programmes was investigated through a national research project (Fraser et al., 2011). The study task addressed in this paper was to establish which roles and responsibilities of lecturers have most impact on student learning and capability as midwives and provide best support for mentors' teaching and assessment decisions. METHODS: Data were collected through United Kingdom (UK) wide survey of Lead Midwives for Education, midwife lecturers and questionnaires and focus groups of student midwives from six case study sites. An activity analysis tool was completed by lecturers in these sites, as well as individual interviews with LMEs and Programme Leads. FINDINGS: The nature of midwife lecturers' engagement with practice is variable and is determined by the particular organisation model used. There is an overall agreement that midwife lecturers have a vital role in supporting the practice based curriculum. Key findings highlight the link lecturer role in supporting students, participating in assessments, supporting mentors and maintaining clinical credibility. Enhancements and deterrents to undertaking the link role are also outlined. These findings are relevant to health care programmes worldwide where clinical practice is an essential component. IMPLICATIONS: contribution to knowledge development about models to support and enhance practice-based learning. PMID- 22051101 TI - Development of a support skill scale in insulin therapy: a nationwide study in Japan. AB - The aim of this cross-sectional, nationwide study in Japan was to develop a support skill scale for insulin therapy (IT-SSS) and to evaluate its validity and reliability. The sample consisted of 1604 nurses at 123 hospitals throughout the country. The factor validity, known-group validity, convergent validity, discriminant validity and internal consistency of IT-SSS were assessed. IT-SSS consisted of 26 minimum and 25 standard support skills. They included 4 subscales for minimum skills: management strategy for hypoglycemia, education about insulin injection technique, individual assessment and support about insulin rejection, and collaboration with medical professionals and patient/family. Three subscales for standard skills: apprehensions concerning the will and emotion of the patient, management for blood glucose control, and coordination in insulin management. Cronbach's alpha coefficient was between 0.75 and 0.90, suggesting strong internal consistency. Multitrait analysis showed that convergent validity was complete, and discriminant validity was found to be almost complete in both minimum and standard skill scales (scaling success rates of 97.6% and 98.7% across all subgroups, respectively). Known group analysis clearly showed that specialist nurses have significantly higher skills than general nurses. These findings indicate that IT-SSS has a reasonable factor validity, convergent validity, discriminant validity, known group validity, and internal consistency. PMID- 22051102 TI - Developing an assessment tool for intended learning outcomes in clinical practice for nursing students. AB - This report describes the development of a new criterion based reference tool to assess nursing knowledge and competence in clinical practice. Nursing education has changed from educating a profession, based on tested experience, to being based on a scientific approach and research based knowledge. Assessment should be capable of measuring whether intended learning outcomes have been reached or not, and if the aims of a course have been fulfilled in order to ensure safe and competent nursing care. The intended learning outcomes from a first year course syllabus were integrated and formed into a three-graded criterion-referenced assessment tool, Assessment of Clinical Education, (AClEd). The AClEd is to be seen as a template, and may be tailor-made in accordance to the objectives, level and criteria of a specific course. The tool showed validity in assessing nursing skills not only the nursing student's ability to perform a task but also, most importantly, the quality of nursing care. PMID- 22051103 TI - Effectiveness of an educational intervention on improving knowledge level of Chinese registered nurses on prevention of falls in hospitalized older people--a randomized controlled trial. AB - Falls are highly prevalent in hospitalized older people. Although many factors contribute to this, registered nurses (RNs) lack of knowledge about how to prevent hospitalized older people falls was identified as one of the major factors. This study explored the effects of an educational intervention on improving knowledge level of RNs on prevention of falls in hospitalized older people. It was a randomized controlled trial. 374 RNs from 4 acute care hospitals in ChongQing were recruited to the study. Data were collected before the intervention and at the 3-month follow-up. After the intervention, knowledge scores increased significantly from baseline in the intervention group and significant differences were detected between the scores of the two groups at the 3-month follow-up. The results reflected that the educational intervention was an effective strategy for improving knowledge level of RNs on prevention of falls in hospitalized older people. PMID- 22051104 TI - Knowledge of congenital heart disease of mothers: presentation of a standardized questionnaire and first results. AB - OBJECTIVE: The "Hannover Inventory of Parental Knowledge of Congenital Heart Disease," a questionnaire for the assessment of knowledge about congenital heart disease (CHD) for use in parents, is presented, and the first results are reported. It consists of eight subscales covering general knowledge of cardiac functioning, signs and symptoms of the child's individual CHD before and after treatment, type of individual CHD and treatment, management of CHD, surveillance of deterioration, endocarditis, and physical activity. DESIGN: One hundred thirty-seven mothers completed the questionnaire immediately after their children underwent CHD surgery. RESULTS: The questionnaire has satisfactory psychometric properties. Knowledge on most dimensions was satisfactory, but it was rather poor with respect to important subscales as endocarditis and surveillance of deterioration. CONCLUSIONS: The questionnaire covers a range of relevant topics by taking the individual CHD into account. Parents have satisfactory knowledge of CHD in some areas, but knowledge about preventive behaviors turned out as rather poor. This needs to be improved in order to make parents capable to take their share of after-treatment care. PMID- 22051105 TI - Deciphering causal and statistical relations of molecular aberrations and gene expressions in NCI-60 cell lines. AB - BACKGROUND: Cancer cells harbor a large number of molecular alterations such as mutations, amplifications and deletions on DNA sequences and epigenetic changes on DNA methylations. These aberrations may dysregulate gene expressions, which in turn drive the malignancy of tumors. Deciphering the causal and statistical relations of molecular aberrations and gene expressions is critical for understanding the molecular mechanisms of clinical phenotypes. RESULTS: In this work, we proposed a computational method to reconstruct association modules containing driver aberrations, passenger mRNA or microRNA expressions, and putative regulators that mediate the effects from drivers to passengers. By applying the module-finding algorithm to the integrated datasets of NCI-60 cancer cell lines, we found that gene expressions were driven by diverse molecular aberrations including chromosomal segments' copy number variations, gene mutations and DNA methylations, microRNA expressions, and the expressions of transcription factors. In-silico validation indicated that passenger genes were enriched with the regulator binding motifs, functional categories or pathways where the drivers were involved, and co-citations with the driver/regulator genes. Moreover, 6 of 11 predicted MYB targets were down-regulated in an MYB siRNA treated leukemia cell line. In addition, microRNA expressions were driven by distinct mechanisms from mRNA expressions. CONCLUSIONS: The results provide rich mechanistic information regarding molecular aberrations and gene expressions in cancer genomes. This kind of integrative analysis will become an important tool for the diagnosis and treatment of cancer in the era of personalized medicine. PMID- 22051106 TI - Cataracts are not associated with retinal detachment in the Bichon Frise in the UK--a retrospective study of preoperative findings and outcomes in 40 eyes. AB - OBJECTIVE: The aim of this study was to evaluate whether the Bichon Frise population in the UK is at the same risk of developing retinal detachment in association with cataract formation and following phacoemulsification as described in reports from the USA. PROCEDURES: The medical records of Bichon Frises which were presented for cataract assessment and of those which were treated with phacoemulsification at Willows Referral Service between 1997 and 2009 were reviewed. RESULTS: Forty eyes (26 dogs) with unilateral or bilateral cataracts were included in the study. There was no evidence of retinal detachment associated with the cataracts at initial presentation. Phacoemulsification was performed on 34 eyes (20 dogs). Clinically evident lens-induced uveitis was treated preoperatively in 17/34 eyes. Artificial lens implantation was carried out in 30/34 eyes; automated anterior vitrectomy was performed in 7/34 eyes. The mean follow-up time was 16.6 months (range 1.5-73 months). At the last re examination, 31/34 eyes (91.2%) were visual. Three eyes (8.8%) were blind--two (in the same dog) because of presumptive bilateral optic nerve disease and one because of uveitis and secondary glaucoma. There was no evidence of retinal detachment following phacoemulsification in any of the 34 eyes. CONCLUSION: This study suggests that the Bichon Frise population in the UK does not appear to have a predisposition for retinal detachment in association with cataract formation or following cataract surgery. Prophylactic random transscleral laser retinopexy or transscleral cryopexy cannot therefore be routinely recommended for Bichon Frises with cataracts in the UK. PMID- 22051108 TI - Performance and penetration of laccase and ABTS inks on various printing substrates. AB - Introduction of an enzyme and a colour-forming reagent into paper enables the development of an authenticity indicator. The purpose of this work was to study the performance of Trametes versicolor laccase, TvL, and ABTS, 2,2'-azino-bis(3 ethylbenzthiazoline-6-sulphonic acid) diammonium salt, in various printing substrates when printed with inkjet. The printing substrates included pre-coated mechanical paper additionally coated with PVA, silica and latex. The focus was on the bioanalytical performance and ink penetration. The setting of the printed TvL and ABTS ink was studied visually, with optical and confocal microscopy and with a so-called tape laminating technique. Technical properties of the printing substrates and effect of the surface chemistry were discussed and related to the bioanalytical properties. TvL activity persisted well during the printing. The best colour response was attained using the PVA-coated base paper. The film forming ability of the PVA was found to be the main contributor to the colour reaction. The uniform, dense and non-porous PVA layer retains the ABTS and TVL molecules on top of the printing substrate. The high local ink concentration on the PVA coating layer combined with the absorptive paper substrate suggests that the PVA film acts as a filtering layer which retains TvL and ABTS molecules in the coating layer but allows most of the ink solvents to penetrate into the paper structure. TvL and ABTS molecules are also trapped in the PVA polymer network due to swelling effect of water. Electrostatic attractions between the PVA and ABTS and TvL molecules do not contribute to the colour reaction. PMID- 22051109 TI - Hakai reduces cell-substratum adhesion and increases epithelial cell invasion. AB - BACKGROUND: The dynamic regulation of cell-cell adhesions is crucial for developmental processes, including tissue formation, differentiation and motility. Adherens junctions are important components of the junctional complex between cells and are necessary for maintaining cell homeostasis and normal tissue architecture. E-cadherin is the prototype and best-characterized protein member of adherens junctions in mammalian epithelial cells. Regarded as a tumour suppressor, E-cadherin loss is associated with poor prognosis in carcinoma. The E3 ubiquitin-ligase Hakai was the first reported posttranslational regulator of the E-cadherin complex. Hakai specifically targetted E-cadherin for internalization and degradation and thereby lowered epithelial cell-cell contact. Hakai was also implicated in controlling proliferation, and promoted cancer related gene expression by increasing the binding of RNA-binding protein PSF to RNAs encoding oncogenic proteins. We sought to investigate the possible implication of Hakai in cell-substratum adhesions and invasion in epithelial cells. METHODS: Parental MDCK cells and MDCK cells stably overexpressing Hakai were used to analyse cell-substratum adhesion and invasion capabilities. Western blot and immunofluoresecence analyses were performed to assess the roles of Paxillin, FAK and Vinculin in cell-substratum adhesion. The role of the proteasome in controlling cell-substratum adhesion was studied using two proteasome inhibitors, lactacystin and MG132. To study the molecular mechanisms controlling Paxillin expression, MDCK cells expressing E-cadherin shRNA in a tetracycline-inducible manner was employed. RESULTS: Here, we present evidence that implicate Hakai in reducing cell-substratum adhesion and increasing epithelial cell invasion, two hallmark features of cancer progression and metastasis. Paxillin, an important protein component of the cell-matrix adhesion, was completely absent from focal adhesions and focal contacts in Hakai overexpressing MDCK cells. The expression of Paxillin was found to be regulated by a proteasome-independent mechanism, possibly due to the decreased abundance of E-cadherin. CONCLUSIONS: Taken together, these results suggest that Hakai may be involved in two hallmark aspects of tumour progression, the lowering cell substratum adhesion and the enhancement of cell invasion. PMID- 22051107 TI - BMP4 signaling directs primitive endoderm-derived XEN cells to an extraembryonic visceral endoderm identity. AB - The visceral endoderm (VE) is an epithelial tissue in the early postimplantation mouse embryo that encapsulates the pluripotent epiblast distally and the extraembryonic ectoderm proximally. In addition to facilitating nutrient exchange before the establishment of a circulation, the VE is critical for patterning the epiblast. Since VE is derived from the primitive endoderm (PrE) of the blastocyst, and PrE-derived eXtraembryonic ENdoderm (XEN) cells can be propagated in vitro, XEN cells should provide an important tool for identifying factors that direct VE differentiation. In this study, we demonstrated that BMP4 signaling induces the formation of a polarized epithelium in XEN cells. This morphological transition was reversible, and was associated with the acquisition of a molecular signature comparable to extraembryonic (ex) VE. Resembling exVE which will form the endoderm of the visceral yolk sac, BMP4-treated XEN cells regulated hematopoiesis by stimulating the expansion of primitive erythroid progenitors. We also observed that LIF exerted an antagonistic effect on BMP4-induced XEN cell differentiation, thereby impacting the extrinsic conditions used for the isolation and maintenance of XEN cells in an undifferentiated state. Taken together, our data suggest that XEN cells can be differentiated towards an exVE identity upon BMP4 stimulation and therefore represent a valuable tool for investigating PrE lineage differentiation. PMID- 22051110 TI - Each type of cause that initiates rheumatoid arthritis or RA flares differentially affects the response to therapy. AB - The autoimmune disease rheumatoid arthritis (RA) presents difficulty in diagnosis, commonly observed flare ups, polycyclical nature of RA progression, and variable response to therapies. Congruent with multiple causes, literature has documented various infectious agents, environmental factors, physical trauma, silica and food sensitivities as potential causes of RA or RA flares in different populations. We propose that these>36 events can initiate RA or RA flares which complicates treatment decisions. Each pharmaceutical medicine benefits 15-82% of RA patients. Predictive factors are needed. Because the initiating cause of RA or RA flare affects the type of joint damage, initial inflammatory response, adaptive immune response, and potential molecular mimicry, we propose the "RA cause affects response to therapy" (RACART) theory. The potential cause combined with confounding factors such as genetic risk factors, nutritional status, epigenetic status, inflammatory levels, and detoxification ability may help predict responses to various therapies. PMID- 22051111 TI - The anabolic benefits of venous blood flow restriction training may be induced by muscle cell swelling. AB - Venous blood flow restriction (VBFR) combined with low intensity resistance exercise (20-30% concentric 1-RM) has been observed to result in skeletal muscle hypertrophy, increased strength, and increased endurance. Knowledge of the mechanisms behind the benefits seen with VBFR is incomplete, but the benefits have traditionally been thought to occur from the decreased oxygen and accumulation of metabolites. Although many of the proposed mechanisms appear valid and are likely true with VBFR combined with resistance exercise, there are certain situations in which benefits are observed without a large accumulation of metabolites and/or large increases in fast twitch fiber type recruitment. Cell swelling appears to be a likely mechanism that appears to be present throughout all studies. VBFR may be able to induce cell swelling through a combination of blood pooling, accumulation of metabolites, and reactive hyperemia following the removal of VBFR which may contribute to skeletal muscle adaptations that occur with VBFR. We hypothesize that cell swelling is important for muscle growth and strength adaptation but when coupled with higher metabolic accumulation, this adaptation is even greater. PMID- 22051112 TI - Visceral obesity, metabolic syndrome, insulin resistance and cancer. AB - This paper presents emerging evidence linking visceral adiposity and the metabolic syndrome (MetSyn) with carcinogenesis. The link between obesity and cancer has been clearly identified in a multitude of robust epidemiological studies. Research is now focusing on the role of visceral adipose tissue in carcinogenesis; as it is recognised as an important metabolic tissue that secretes factors that systemically alter the immunological, metabolic and endocrine milieu. Excess visceral adipose tissue gives rise to a state of chronic systemic inflammation with associated insulin resistance and dysmetabolism, collectively known as the MetSyn. Prospective cohort studies have shown associations between visceral adiposity, the MetSyn and increased risk of breast cancer, colorectal cancer and oesophageal adenocarcinoma. Furthermore, visceral adiposity and the MetSyn have been associated with increased tumour progression and reduced survival. The mechanisms by which visceral adiposity and the MetSyn are thought to promote tumorigenesis are manifold. These include alterations in adipokine secretion and cell signalling pathways. In addition, hyperinsulinaemia, subsequent insulin resistance and stimulation of the insulin-like growth factor-1 axis have all been linked with visceral adiposity and promote tumour progression. Furthermore, the abundance of inflammatory cells in visceral adipose tissue, including macrophages and T-cells, create systemic inflammation and a pro tumorigenic environment. It is clear from current research that excess visceral adiposity and associated dysmetabolism play a central role in the pathogenesis of certain cancer types. Further research is required to elucidate the exact mechanisms at play and identify potential targets for intervention. PMID- 22051113 TI - Increase in endoplasmic reticulum-associated tissue transglutaminase and enzymatic activation in a cellular model of Parkinson's disease. AB - Parkinson's disease (PD) is characterized by accumulation of alpha-synuclein aggregates and degeneration of melanized, catecholaminergic neurons. The tissue transglutaminase (tTG) enzyme catalyzes molecular protein cross-linking. In PD, tTG levels are increased and cross-linking has been identified as an important factor in alpha-synuclein aggregation. In our quest to link tTGs distribution in the human brain to the hallmarks of PD pathology, we recently reported that catecholaminergic neurons in PD disease-affected brain areas display typical endoplasmic reticulum (ER) granules showing tTG immunoreactivity. In the present study, we set out to elucidate the nature of the interaction between tTG and the ER in PD pathogenesis, using retinoic-acid differentiated SH-SY5Y cells exposed to the PD-mimetic 1-methyl-4-phenylpyridinium (MPP(+)). Alike our observations in PD brain, MPP(+)-treated cells displayed typical TG-positive granules, that were also induced by other PD mimetics and by ER-stress inducing toxins. Additional immunocytochemical and biochemical investigation revealed that tTG is indeed associated to the ER, in particular at the cytoplasmic face of the ER. Upon MPP(+) exposure, additional recruitment of tTG toward the ER was found. In addition, we observed that MPP(+)-induced tTG activity results in transamidation of ER membrane proteins, like calnexin. Our data provide strong evidence for a, so far unrecognized, localization of tTG at the ER, at least in catecholaminergic neurons, and suggests that in PD activation of tTG may have a direct impact on ER function, in particular via post-translational modification of ER membrane proteins. PMID- 22051114 TI - Effect of platelet-derived growth factor-BB on root resorption after reimplantation of partially denuded tooth in dog. AB - The prognosis for a reimplanted tooth depends largely on the condition of the root. Platelet-derived growth factor (PDGF)-BB has been shown to regenerate periodontal tissue in animal and human clinical studies. However, information regarding the effect of PDGF-BB on tooth reimplantation is limited. The objective of this study was to investigate the effect of PDGF-BB on root resorption after reimplantation of a partially denuded tooth in dog. A total of 15 healthy female beagle dogs were used. Mandibular third and fourth premolars were endodontically treated and then extracted as atraumatically as possible. The coronal portion of each root was carefully scaled and planed. The roots on the right side of the mandible were treated with PDGF-BB and reimplanted, while the roots on the left side served as controls. After 2, 4, or 8 weeks, specimens were collected and processed for histopathological examination. By the 4th week after reimplantation, new periodontal ligament (PDL)-like tissue had formed around the PDGF-BB-treated root surfaces and new bone. By the 8th week, healing of the PDGF BB-treated roots was characterized by newly formed PDL with inserting attachment formation. In contrast, control roots showed multiple areas of replacement resorption. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) performed at 2 weeks after reimplantation showed that the number of PCNA positive cells in the connective tissue area was statistically significantly greater in the PDGF-BB-treated group than in the control group (P < 0.001). The application of PDGF-BB resulted in a significantly lower occurrence and extent of root resorption and ankylosis. These results suggest that the use of PDGF-BB reduces occurrence of ankylosis and root resorption in tooth reimplantation. PMID- 22051116 TI - Metabolic effects of bariatric surgery in type 2 diabetic patients with body mass index < 35 kg/m2. AB - AIM: The aim of this meta-analysis is to assess the metabolic effects of bariatric surgery in type 2 diabetes mellitus (T2DM) patients with body mass index (BMI) < 35 kg/m(2) . METHODS: We performed an electronic literature search of published articles to identify relevant evidence since inception to June 2011. Primary outcome measures were metabolic improvement and resolution diabetes after bariatric surgery. The weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated from the raw data extracted from the original literature. The software Review Manager (version 4.3.1) was applied for meta analysis. RESULTS: Thirteen trials involving 357 patients were included in the meta-analysis. The follow-up interval ranged from 6 months to 18 years. According to WMD calculation, bariatric surgery led to 5.18 kg/m(2) of BMI lowering (95% CI, 3.79-6.57, p < 0.00001), 4.8 mmol/l of fasting plasma glucose (FPG) decrement (95% CI, 3.88-5.71 mmol/l, p < 0.00001), 2.59% of HbA1c decreasing (95% CI, 2.12 3.07%, p < 0.00001), 56.67 mg/dl of triglyceride decrement (95% CI 11.53-101.82, p = 0.01) and 48.38 mg/dl of total cholesterol reduction (95% CI 21.08-75.68, p = 0.0005). Moreover, the procedures produced an increased high-density lipoprotein cholesterol by 5.37 mg/dl (95% CI -11.37-0.63, p = 0.08). However, this effect was not statistically significant. Overall, 80.0% of the patients achieved adequate glycaemic control (HbA1c < 7%) without antidiabetic medication. The surgeries produced a low incidence of major complications (3.2%) with no mortality. CONCLUSIONS: Bariatric surgery is effectual and safe in the treatment of non-severely obese (BMI < 35 kg/m(2) ) T2DM patients. Moreover, the metabolic benefits acquired from the procedures can be long sustained after the surgery. PMID- 22051117 TI - New insights into the functions and localization of nuclear transglutaminase 2. AB - Transglutaminase 2 (TG2; EC 2.3.2.13) is the most abundantly expressed member of the transglutaminase family and exerts opposing effects on cell growth, differentiation and apoptosis via multiple activities, including transamidase, GTPase, cell adhesion, protein disulfide isomerase, kinase and scaffold activities. It is distributed in and around various parts of a cell, including the extracellular matrix, plasma membrane, cytosol, mitochondria and nucleus. Generally, nuclear TG2 represents only 5-7% of the total TG2 in a cell, and various stimuli will increase nuclear TG2 via cellular stress and/or an increased intracellular Ca(2+) concentration. There is increasing evidence indicating the importance of nuclear TG2 in regulating gene expression via post-translational modification of (or interaction with) transcriptional factors and related proteins. These include E2F1, hypoxia inducible factor 1, Sp1 and histones. Through this mechanism, TG2 controls cell growth or survival, differentiation and apoptosis, and is involved in the pathogenesis and/or treatment of neurodegenerative diseases, liver diseases and cancers. The balance between import from the cytoplasm to the nucleus, and export from the nucleus to the cytoplasm, determines the level of TG2 in the nucleus. Selective regulation of the expression, activity or localization of nuclear TG2 will be important for basic research, as well as clinical applications, suggesting a new era for this long-studied enzyme. PMID- 22051115 TI - Chronic alloantibody mediated rejection. AB - Alloantibodies clearly cause acute antibody mediated rejection, and all available evidence supports their pathogenic etiology in the development of chronic alloantibody mediated rejection (CAMR). But the slow evolution of this disease, the on-going immunosuppression, the variations in titer of alloantibodies, and variation in antigenic targets all complicate identifying which dynamic factors are most important clinically and pathologically. This review highlights the pathological factors related to the diagnosis of CAMR, the time course and natural history of this disease. What is known about CAMR pathogenesis is discussed including alloantibodies, the role of complement, gene activation, and Fc effector cell function. Therapy, which is problematic for this disease, is also discussed, including on-going and potential therapies and their limitations. PMID- 22051118 TI - Social anxiety disorder in genuine halitosis patients. AB - BACKGROUND: There is a possibility that genuine halitosis patients' anxiety do not recover after oral malodor treatment due to their social anxiety disorder. The objective of this study was to investigate the influence of social anxiety disorder on the level of anxiety in genuine halitosis patients before and after treatment for oral malodor. METHODS: The subjects were 262 genuine halitosis patients who visited the Fresh Breath Clinic from March, 2008 to October, 2009. The subjects who had score 2 or higher by the organoleptic test were diagnosed as genuine halitosis patients. Gas chromatography (GC) was conducted before and after oral malodor treatment for the oral malodor measurement. Based on their risk of social anxiety disorder, subjects were divided into low- and high-risk groups using the Liebowitz Social Anxiety Scale (LSAS). The questions related to oral malodor and the clinical oral examination were both conducted before oral malodor treatment. The level of anxiety before and after oral malodor treatment was evaluated using the Visual Analogue Scale of Anxiety (VAAS). RESULTS: More than 20% of subjects had a score of 60 or more on the LSAS (high LSAS group). The mean age and the percentage of females were significantly higher in the high LSAS group compared to the low LSAS group. The high LSAS group was more likely to have problems associated with oral malodor and to adopt measures against oral malodor compared to the low LSAS group. The mean concentrations of H2S and CH3SH by GC significantly decreased after the oral malodor treatment in both LSAS groups. VAAS scores also significantly decreased after treatment in both LSAS groups. The logistic regression analysis indicated that the high LSAS group had a 2.28 times higher risk of having a post-VAAS score of 50 or more compared to the low LSAS group. CONCLUSIONS: This study revealed that genuine halitosis patients with a strong trait of social anxiety disorder have difficulty overcoming their anxiety about oral malodor. Oral malodor treatment of genuine halitosis patients requires not only regular oral malodor treatment but also attention to social anxiety disorder. PMID- 22051119 TI - Nutritional risk screening in surgery: valid, feasible, easy! AB - BACKGROUND & AIMS: We aimed to test the capacity in identifying patients at nutritional risk, by comparing BMI, recent %weight loss,Nutritional Risk Screening 2002(NRS-2002),Malnutrition Universal Screening Tool(MUST) and Nutritional Risk Index(NRI) with Subjective Global Assessment(SGA),considered the Standard. The main purpose was to select the most consistent screening method for effective integration in daily surgical wards' practice. METHODS: 300 surgical patients were assessed at admission: BMI(categorized by WHO's criteria), weight loss >= 5% in previous 6 months, NRS-2002, MUST, NRI, SGA. Concordances, correlations, sensitivity, specificity, positive(PPV) and negative predictive values(NPV) were calculated to evaluate methods' performance vs the Standard. RESULTS: Prevalence of nutritional risk was 66% by NRS-2002 + MUST, and 87% by NRI. By SGA, 64% patients were undernourished. All methods agreed with SGA(k = 0.85-0.91,p < 0.001), except BMI & NRI(k = 0.07-0.34,p < 0.05). NRS-2002, MUST and %weight loss effectively detected patients at risk: sensitivity 0.8-0.89, specificity 0.89-0.93, PPV 81%-89%, NPV 89%-100%. Conversely, BMI & NRI were ineffective: sensitivity 0.29-0.43, specificity 0.27-0.39, PPV 24%-35%, NPV 27% 31%; %weight loss alone vs MUST/NRS-2002 was explored: sensitivity 0.79-0.87, specificity 0.85-0.89, PPV 84%-85%, NPV 87%-89%, thus successfully identifying undernutrition risk. CONCLUSIONS: In surgical patients, MUST + NRS-2002 are valid for nutritional screening; recent weight loss >= 5% also proved highly efficient; its easy/quick calculation may facilitate adherence/integration by health professionals as a minimum obligatory in clinical practice. PMID- 22051120 TI - Examination of the anterior uveoscleral pathway in domestic species. AB - OBJECTIVE: To investigate the uveoscleral (US) pathway in the normal eyes of four domestic spp.: the cat, pig, cow and horse by examining the comparative anatomical structure of anterior US pathway. ANIMALS STUDIED: Four cats, ten pigs, four cows, eight horses. PROCEDURES: Formalin-preserved specimens from anterior uveas of the cat, pig, cow and horse were embedded and serially sectioned sagittally and tangentially and stained with H&E, Masson's trichrome, smooth muscle actin immunolabel, or elastin stain. RESULTS: Spaces between the endings of the outer anterior ciliary body musculature (CBM) formed avenues for the beginning of the US pathway and varied in the amount of extracellular matrix (ECM) material being most developed in the pig. In the cow, other anterior muscle bundles attached the CBM to the sclera concomitant with the presence of an anterior elastic sheath. In the horse, these muscle bundles were connected to branching connective tissue trabeculae within the US pathway that were attached radially to the sclera. In the cat, muscle bundles were more abundant and formed a fine meshwork of trabecular associations with the posterior ICA. Supraciliary development was most pronounced in the horse and least in the pig. CONCLUSION: All species possessed clearly developed and unique US pathways. The outermost muscle bundles of the CBM appeared to have close interaction with the US pathway and the degree of these muscle associations differed with species. The species specific anatomical variations within the US pathway could play a pivotal role in the variability of aqueous outflow along this pathway. PMID- 22051121 TI - Challenges associated with curcumin therapy in Alzheimer disease. AB - Curcumin, the phytochemical agent in the spice turmeric, which gives Indian curry its yellow colour, is also a traditional Indian medicine. It has been used for millennia as a wound-healing agent and for treating a variety of ailments. The antioxidant, anti-inflammatory, antiproliferative and other properties of curcumin have only recently gained the attention of modern pharmacology. The mechanism of action of curcumin is complex and multifaceted. In part, curcumin acts by activating various cytoprotective proteins that are components of the phase II response. Over the past decade, research with curcumin has increased significantly. In vitro and in vivo studies have demonstrated that curcumin could target pathways involved in the pathophysiology of Alzheimer disease (AD), such as the beta-amyloid cascade, tau phosphorylation, neuroinflammation or oxidative stress. These findings suggest that curcumin might be a promising compound for the development of AD therapy. However, its insolubility in water and poor bioavailability have limited clinical trials and its therapeutic applications. To be effective as a drug therapy, curcumin must be combined with other drugs, or new delivery strategies need to be developed. PMID- 22051122 TI - Writing academic papers: lost in translation? AB - The process of writing for publication is a challenging one. It moves us from the spoken and written word into a realm that requires us to provide supporting evidence to develop an argument in a logical and progressive way. In English language journals, as elsewhere, the quality of the written word is a determining factor in the likelihood of a paper being accepted for publication. By reading past issues of a targeted journal, drawing on the expertise of colleagues and responding positively to feedback, it is possible to significantly enhance your prospects of publication. PMID- 22051123 TI - Cost-effective ways of delivering enquiry services: a rapid review. AB - BACKGROUND: In the recent times of recession and budget cuts, it is more important than ever for library and information services to deliver cost effective services. OBJECTIVES: This rapid review aims to examine the evidence for the most cost-effective ways of delivering enquiry services. METHODS: A literature search was conducted on LISA (Library and Information Sciences Abstracts) and MEDLINE. Searches were limited to 2007 onwards. RESULTS: Eight studies met the inclusion criteria. The studies covered hospital and academic libraries in the USA and Canada. Services analysed were 'point-of-care' librarian consultations, staffing models for reference desks and virtual/digital reference services. CONCLUSIONS: Transferable lessons, relevant to health library and information services generally, can be drawn from this rapid review. These suggest that 'point-of-care' librarians for primary care practitioners are a cost effective way of answering questions. Reference desks can be cost-effectively staffed by student employees or general reference staff, although librarian referral must be provided for more complex and subject-specific enquiries. However, it is not possible to draw any conclusions on virtual/digital reference services because of the limited literature available. Further case analysis studies measuring specific services, particularly enquiry services within a health library and information context, are required. PMID- 22051124 TI - A review and rationalisation of journal subscriptions undertaken by a library and information service in a mental health trust in north-east England in 2009. AB - AIM: To describe the methods and processes used in an evaluation of local journal subscriptions in a mental health trust and to suggest possible further areas of investigation were similar exercises to be undertaken again. METHOD AND RESULTS: Results from a user questionnaire were analysed along with e-journal usage statistics and data from local document supply activity. CONCLUSIONS: Journal reviews can yield surprising results. Carrying out a user survey is valuable in highlighting awareness of e-resources more generally and thus in providing evidence for marketing/information literacy initiatives. Future journal reviews should undertake impact analysis as potent evidence for continued expenditure on journals in this age of austerity. PMID- 22051125 TI - Integrating evidence-based practice and information literacy skills in teaching physical and occupational therapy students. AB - BACKGROUND: To ensure that physical and occupational therapy graduates develop evidence-based practice (EBP) competencies, their academic training must promote EBP skills, such as posing a clinical question and retrieving relevant literature, and the information literacy skills needed to practice these EBP skills. OBJECTIVE: This article describes the collaborative process and outcome of integrating EBP and information literacy early in a professional physical therapy and occupational therapy programme. METHODS: The liaison librarian and a faculty member designed an instructional activity that included a lecture, workshop and assignment that integrated EBP skills and information literacy skills in the first year of the programme. The assignment was designed to assess students' ability to conduct a search independently. RESULTS: The lecture and workshop were successful in their objectives, as 101 of the 104 students received at least 8 out of 10 points on the search assignment. CONCLUSIONS: The teaching activities developed for the students in this course appear to have achieved the goal of teaching students the EBP research cycle so that they might begin to emulate it. The collaboration between the faculty member and the librarian was integral to the success of this endeavour. Future work will include the evaluation of students' long-term retention of information literacy objectives. PMID- 22051126 TI - Effectiveness of bibliographic searches performed by paediatric residents and interns assisted by librarians. A randomised controlled trial. AB - BACKGROUND: Considerable barriers still prevent paediatricians from successfully using information retrieval technology. OBJECTIVES: To verify whether the assistance of biomedical librarians significantly improves the outcomes of searches performed by paediatricians in biomedical databases using real-life clinical scenarios. METHODS: In a controlled trial at a paediatric teaching hospital, nine residents and interns were randomly allocated to an assisted search group and nine to a non-assisted (control) group. Each participant searched PubMed and other online sources, performing pre-determined tasks including the formulation of a clinical question, retrieval and selection of bibliographic records. In the assisted group, participants were supported by a librarian with >=5 years of experience. The primary outcome was the success of search sessions, scored against a specific assessment tool. RESULTS: The median score of the assisted group was 73.6 points interquartile range (IQR = 13.4) vs. 50.4 (IQR = 17.1) of the control group. The difference between median values in the results was 23.2 points (95% CI 4.8-33.2), in favour of the assisted group (P value, Mann-Whitney U test: 0.013). CONCLUSIONS: The study has found quantitative evidence of a significant difference in search performance between paediatric residents or interns assisted by a librarian and those searching the literature alone. PMID- 22051127 TI - Evidence-based medicine: is the evidence out there for primary care clinicians? AB - BACKGROUND: Finding evidence to answer clinical questions is essential to the practice of evidence-based medicine (EBM). However, practising EBM in primary care is thought to be problematic because of concerns about whether evidence exists to answer specific questions. OBJECTIVES: To determine the highest level of evidence per question; to ascertain the number of questions unanswered because of a lack of evidence; to establish the frequency with which guidelines answered questions; and to determine the domain of websites used to answer questions. METHODS: Clinical questions were identified from two primary care answering services: ATTRACT and National Library for Health (NLH) Primary Care Answering Service. The types of evidence used to answer the question were noted, including whether this was from systematic reviews or meta-analyses (level one evidence) or from randomised controlled trials (level two). The data were collected from March to June 2008. RESULTS: Level 1 or level 2 evidence answered 11% of questions. Sixteen per cent were unanswered because of a lack of evidence. Over 40% of questions were answered using guidelines. Forty-three per cent of questions were answered with one type of evidence and 24% with two. CONCLUSION: Guidelines are useful resources for primary care clinicians, answering two-fifths of questions. PMID- 22051128 TI - Evaluating the quality of websites relating to diet and eating disorders. AB - OBJECTIVE: To verify whether the Credibility Indicator is able to evaluate the quality of websites. METHOD: This is a descriptive cross-sectional study of websites on diet and anorexia/bulimia, using searches on Google to access the study population. Quality was studied using 22 variables selected by consolidating international proposals. In addition, eight variables belonging to the Credibility Indicator were also studied. RESULTS: Three hundred and fifty four homepages relating to diet and 366 homepages relating to anorexia/bulimia were evaluated. None of the websites met all of the quality criteria; neither did any website satisfy all of the Credibility Indicators. A positive correlation was observed between fulfilment of the Quality items and the Credibility Indicator (R = 0.72; P < 0.001). Significant differences were found in the fulfilment of the Total Quality variables between the websites that had these variables and those that did not (t-test = -9.91, P < 0.001). CONCLUSIONS: The quality of websites covering issues of diet and anorexia/bulimia is still poor. The Credibility Indicator is a useful aid when determining the quality of a website. It is evident that identifying authorship and affiliation is an important factor in predicting the quality of the information. PMID- 22051129 TI - A study of the information seeking behaviour of hospital pharmacists: empirical evidence from Greece. AB - BACKGROUND: Hospital pharmacists need access to high-quality information in order to constantly update their knowledge and improve their skills. In their modern role, they are expected to address three types of challenges: scientific, organizational and administrative, thus having an increased need for adequate information and library services. OBJECTIVES: This study investigates the information-seeking behaviour of public hospital pharmacists providing evidence from Greece that could be used to encourage the development of effective information hospital services and study the links between the information seeking behaviour of hospital pharmacists and their modern scientific and professional role. METHOD: An empirical research was conducted between January and February 2010 with the development and distribution of a structured questionnaire. The questionnaire was filled in and returned by 88 public hospital pharmacists from a total of 286 working in all Greek public hospitals, providing a response rate of 31%. RESULTS: The hospital pharmacists in Greece are in search of scientific information and, more particularly, pharmaceutical information (e.g., drug indications, storage, dosage and prices). The Internet and the National Organization of Medicines are their main information sources, while the lack of time and organized information are the main obstacles they have to face when seeking information. CONCLUSIONS: The modern professional role of hospital pharmacists as invaluable contributors to efficient and safer healthcare services may be further supported through the development of specialized libraries and information services within Greek public hospitals. PMID- 22051131 TI - Trend spotting--whither health science librarianship? AB - This feature surveys 20th-century trends in health sciences librarianship. It sets the scene for a series of features looking at 21st-century trends in various countries and regions. Whilst the mission of the health science library remains constant, librarians must find ways of adjusting their role and the services they provide to take account of changes in the external environment. PMID- 22051130 TI - Physicians utilisation of internet medical databases at the tertiary health institutions in Osun State, south west, Nigeria. AB - OBJECTIVES: To determine the extent, purpose, determinants and the impact of the utilization of Internet medical databases among the respondents. METHODOLOGY: A descriptive cross sectional survey of 540 randomly selected physicians at the two tertiary health institutions in Osun State, south west, Nigeria. RESULT: A total of 444 (82.2%) physicians completed the questionnaires. All the respondents have used the internet medical databases within the last 4 weeks of the study. Majority, (53.8%) used the internet resources at least once in 2 weeks, while 12.2% used the resources every day. The online resources are mainly sought for Routine patient care and for Research purposes. pubmed (70.3%), hinari (69.0%), and Free medical journals (60.1%) are the frequently used online databases/digital archives. The internet resources has positively impacted the Clinical practice (40.0%) and Research output (65.5%) of the physicians. CONCLUSION: There had been considerable increase in the extent and quality of utilization of online medical databases which has positively impacted on the Clinical practice and Research output of the physicians. Ease of finding the needed information and the availability of evidence based resources are the major determinants of the databases utilized. PMID- 22051132 TI - Health librarians: developing professional competence through a 'legitimate peripheral participation' model. AB - This feature considers the legitimate peripheral participation model in developing professional competencies in health librarianship. It is described how this model was used in the development of a framework for mapping and recognising the competencies gained by new health librarians at the Royal Free Hospital Medical Library. HS. PMID- 22051133 TI - Bridging the 'Know-do gap': a role for health information professionals? AB - This feature briefly examines the development of knowledge translation, knowledge transfer and the knowledge broker role as constituting the next manifestation of the movement that brought us evidence based medicine and its derivatives. It examines the extent to which health information professionals currently meet the specification for a knowledge broker role. In doing so it assesses the strengths and weaknesses of the profession when ranged alongside the five components of the knowledge transfer process that is, problem identification; knowledge development and selection; analysis of context; knowledge transfer interventions; and knowledge utilization. Current deficiencies also lie in a need for political astuteness and awareness and in a lack of knowledge of the most significant models of behavioural change. The feature concludes by examining the potential for knowledge team approaches arguing that gains from a wider perspective that encompasses the entire knowledge process may be even more significant than the pooling of collective knowledge, skills and expertise. PMID- 22051135 TI - Methods in vaccine effectiveness and safety studies: a critical need for vaccine confidence. PMID- 22051136 TI - Intranasal administration of a flagellin-adjuvanted inactivated influenza vaccine enhances mucosal immune responses to protect mice against lethal infection. AB - The influenza virus, a mucosal pathogen that infects the respiratory tract, is a major global health issue. There have been attempts to mucosally administer inactivated influenza vaccines to induce both mucosal and systemic immune responses. However, mucosally administered inactivated influenza vaccine has low immunogenicity, which is partially due to the lack of an effective mucosal adjuvant. The development of a safe and effective mucosal adjuvant is a prerequisite to the practical use of a mucosal inactivated influenza vaccine. We have previously demonstrated that a bacterial flagellin, Vibrio vulnificus FlaB, when mixed with antigen and administered intranasally, exerts a strong mucosal adjuvant activity by stimulating the Toll-like receptor 5 (TLR5). In this study, we tested whether the FlaB protein could serve as an effective mucosal adjuvant for an inactivated trivalent influenza vaccine (TIV) manufactured for humans; in a murine vaccination model, this vaccine consists of A/Brisbane/59/07 (H1N1 subtype), A/Uruguay/716/07 (H3N2 subtype), and B/Florida/4/06 (B type). Intranasal co-administration of the TIV with FlaB induced prominent humoral responses as demonstrated by high influenza-specific IgA levels in both the mucosal secretions and serum and significant specific IgG induction in the systemic compartment. The FlaB protein significantly potentiated influenza specific cytokine production by draining lymph node cells and splenocytes. The FlaB mucosal adjuvant conferred excellent protection against a lethal challenge with a live virulent virus with high hemagglutination inhibition (HAI) antibody (Ab) titers. The FlaB did not accumulate in the olfactory nerve and epithelium, guaranteeing against a retrograde uptake into the central nervous system. These results suggest that FlaB can be used as a promising mucosal adjuvant for nasal inactivated influenza vaccine development. PMID- 22051137 TI - Influence of in vitro hemolysis on hematological testing on Advia 2120. AB - INTRODUCTION: Although there is broad knowledge on the effect of several preanalytical errors on laboratory hematology, there is no information on the reliability of routine hematological testing on hemolyzed specimens. METHODS: K(2) EDTA-anticoagulated blood collected from 13 healthy volunteers was divided in three aliquots. Aliquot A did not undergo further manipulation, while the second and third aliquots (B and C, respectively) were passed 5 and 10 times through a small-gauge needle to produce scalar amounts of hemolysis. Hematological testing was first performed on Advia 2120. The plasma was then separated by centrifugation and tested for lactate dehydrogenase and hemolysis index (HI). RESULTS: As compared with the nonhemolyzed aliquot, analytically and clinically significant variations were recorded in both mildly and frankly hemolyzed specimens for lactate dehydrogenase, HI, red blood cells count, hematocrit, mean corpuscular volume, mean hemoglobin content, lymphocytes, basophils, and large unstained cells. Both the platelets count and the mean platelet volume were also dramatically affected. The other parameters tested (hemoglobin, red blood cell distribution width, neutrophils, and eosinophils) did not vary significantly. CONCLUSION: The results of routine hematological testing on mildly to frankly hemolyzed specimens might be unreliable. PMID- 22051138 TI - A non-healing corneal ulcer as the presenting feature of type 1 diabetes mellitus: a case report. AB - INTRODUCTION: Diabetic keratopathy is a rare complication of diabetes mellitus. This case illustrates the importance of checking blood sugar levels of patients with non-healing corneal ulcers to rule out the possibility of undiagnosed diabetes mellitus. CASE PRESENTATION: We report the unusual case of a 24-year-old southeast Asian woman who presented with a sterile corneal ulcer to our hospital and later was found to be diabetic after a prolonged hospital stay. Despite all efforts, the corneal ulcer had failed to heal until treatment for previously undiagnosed diabetes was started. The sterile corneal ulcer began to heal once blood sugar levels began to normalize. CONCLUSIONS: Diabetic keratopathy is a rare complication of diabetes mellitus and needs to be considered as a diagnosis in younger patients with non-healing sterile corneal ulcers. Blood sugar levels should be checked in these cases for undiagnosed diabetes mellitus. PMID- 22051139 TI - A retrospective study of the clinical, histological, and immunohistochemical manifestations of 5 dogs originally diagnosed histologically as necrotizing scleritis. AB - PURPOSE: To describe the clinical, histological, and immunohistochemical manifestations of canine necrotizing scleritis. METHODS: A retrospective examination of the clinical records and samples of ocular tissues from five dogs with a histological diagnosis 'necrotizing scleritis' was completed. Archived, formalin-fixed, paraffin-embedded samples and two control globes were stained with hematoxylin and eosin, Gram, periodic acid-Schiff (PAS) and Masson trichrome stains, and they were immunohistochemically labeled for CD3, CD18, and CD20. RESULTS: Of the five cases reviewed, only two could be confirmed as idiopathic necrotizing scleritis. The other three cases were retrospectively diagnosed as unilateral focal, non-necrotizing scleritis, one as episcleritis and the third was scleritis secondary to a proptosed globe based on our retrospective clinical, histological, and immunohistochemical evaluations. In these two cases, idiopathic necrotizing scleritis manifested as a bilateral, progressive, inflammatory disease of the sclera and cornea that induces significant uveitis. Light microscopic examination confirmed collagen degeneration and granulomatous inflammation. There was no evidence for an infectious etiology based on Gram's and PAS stainings. Immunohistochemical labeling revealed a predominance of B cells in idiopathic, bilateral necrotizing scleritis. Tinctorial staining abnormalities with Masson's trichrome stain were present in scleral collagen of the two cases with idiopathic necrotizing scleritis as well as a case of secondary traumatic scleritis. CONCLUSIONS: Based on a limited number of cases, idiopathic canine necrotizing scleritis shares similar histopathological features with non-necrotizing scleritis and episcleritis; however, necrotizing scleritis is B-cell-dominated and bilateral, and significant collagen alterations manifest with Masson's trichrome stain. PMID- 22051140 TI - Plasma pseudo cholinesterase deficiency leading to seven hour apnoea in a child undergoing adeno-tonsillectomy. AB - OBJECTIVE: We report a rare, silent, potentially fatal operative complication of seven hour apnoea in a patient undergoing adenotonsillectomy secondary to deficiency of plasma cholinesterase. Awareness of this hereditary disorder is important to otolaryngologist as; it is difficult to diagnose, can be unexpectedly alarming for parents and the surgeon. METHODS: Case report and review of world literature. RESULTS: A four-year male with obstructive sleep apnoea underwent a routine elective adenotonsillectomy; there was no spontaneous recovery of respiration following surgery. He was transferred to the intensive care unit and 7 h later was successfully weaned from the ventilator and extubated. A plasma cholinesterase level of 456 1U/L was discovered much later. CONCLUSION: To our knowledge this is the first case report of pseudo cholinesterase deficiency reported in otolaryngology literature and first in Oman. The patient should receive information about the condition, the associated risks, inheritance and need for testing other family members. PMID- 22051141 TI - Clinical spectrum of acute rhinosinusitis among atopic and nonatopic children in Taiwan. AB - BACKGROUND: Rhinitis and sinusitis are very common medical conditions and have been shown to be frequently associated. The role of allergies in the pathogenesis of chronic rhinosinusitis has been confirmed; however, the role of allergies in acute rhinosinusitis is debatable. Nonetheless, allergies are an important factor in the development of rhinosinusitis. OBJECTIVE: To evaluate the incidence of allergic rhinitis in patients with acute rhinosinusitis and identify the clinical spectrum in Taiwan. METHODS: This study randomly recruited 69 participants between 3 and 12 years of age with acute rhinosinusitis over the period of one and a half years. All participants underwent a nasal peak expiratory flow rate (nPEFR) test, skin-Prick test (SPT), nasal smear examination, nasal culture, radiography (Water's projection) and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) as well as provide their allergic history. RESULTS: Among the 69 participants in the study, 27 (39.1%) participants were shown to have allergic rhinitis. The most troublesome symptoms among the 69 participants with acute rhinosinusitis were postnasal drip (3.00 +/- 1.29), nasal obstruction (2.94 +/- 1.39) and cough (2.67 +/- 1.42). The most troublesome symptoms among the 27 participants with acute rhinosinusitis combined with allergic rhinitis were nasal obstruction (3.33 +/- 1.24), postnasal drip (3.22 +/- 1.09) and itchy eyes (2.74 +/- 1.43) and with the higher values. In addition, the participants (? 6 y/o) with acute rhinosinusitis combined with allergic rhinitis had significantly lower nPEFR values compared with the nonatopic children (75.2 +/- 18.2 vs 96.6 +/- 21.4, p<0.05). If nPEFR is below 75 mL/min, the positive predict value in the patients of acute rhinosinusitis is 75.0% combined with allergic rhinitis (sensitivity 63.2%; specificity 85.7%). Streptococcus pneumoniae (29.0%), Haemophilus influenzae (20.3%), and Moraxella catarrhalis (17.4%) were the major isolated pathogens in this study. The prevalence of colonization with Staphylococcus aureus in the 69 participants with acute rhinosinusitis was 23.2%, and 15.9% for methicillin-resistant S. aureus (MRSA). CONCLUSION: This study demonstrated that the bacteriological properties of acute rhinosinusitis among children in Taiwan are the same as those in other parts of the world; however, the prevalence of colonization by MRSA was higher than among healthy children. Second, atopic children were more likely to develop acute rhinosinusitis than nonatopic children. Third, most Taiwanese children with acute rhinosinusitis complained of postnasal drip, nasal obstruction and cough. If a child suffering from acute rhinosinusitis complained of severe nasal obstruction (nPEFR?75 mL/min), the doctor should be alerted to atopic conditions requiring further treatment. The issues dealt with in this study may require further research with a larger sample population over an extended period of time to verify these conclusions. PMID- 22051142 TI - Short-term vs long-term calcium hydroxide therapy after immediate tooth replantation: a histomorphometric study in monkey's teeth. AB - Endodontic treatment is an important step of tooth replantation protocols, but the ideal moment for definitive obturation of replanted teeth has not yet been established. In this study, a histomorphometric analysis was undertaken to evaluate the repair process on immediate replantation of monkey's teeth after calcium hydroxide (CH) therapy for 1 and 6 months followed by root canal filling with a CH-based sealer (Sealapex((r)) ). The maxillary and mandibular lateral incisors of five female Cebus apella monkeys were extracted, kept in sterile saline for 15 min, replanted and splinted with stainless steel orthodontic wire and composite resin for 10 days. In Group I (control), definitive root canal filling was performed before tooth extraction. In Groups II and III, CH therapy started after removal of splint, and definitive root canal filling was performed 1 and 6 months later, respectively. The animals were euthanized 9 months after replantation, and specimens were processed for histomorphometric analysis. In all groups, epithelial attachment occurred at the cementoenamel junction or very close to this region; the areas of resorption on root surface had small extension and depth and were repaired by newly formed cementum; and the periodontal ligament was organized. Statistical analysis of the scores obtained for the histomorphometric parameters did not show any statistically significant difference (P = 0.1221) among the groups. The results suggests that when endodontic treatment is initiated 10 days after immediate replantation and an antibiotic regimen is associated, definitive root canal filling can be performed after a short-term CH therapy. PMID- 22051143 TI - A cost-effectiveness analysis of a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy. AB - BACKGROUND: Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective. METHODS: A Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research. RESULTS: PREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to ?41,986 and for PREP to ?42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least ?3,200/QALY. At the prevailing threshold of ?20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty. CONCLUSIONS: Based on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till ?45,906/QALY). PMID- 22051144 TI - Nutritional influences on epigenetics and age-related disease. AB - Nutritional epigenetics has emerged as a novel mechanism underlying gene-diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modulates gene expression without changes in the underlying bp sequence, ultimately determining phenotype from genotype. DNA methylation and post-translational histone modifications are classical levels of epigenetic regulation. Epigenetic phenomena are critical from embryonic development through the aging process, with aberrations in epigenetic patterns emerging as aetiological mechanisms in many age-related diseases such as cancer, CVD and neurodegenerative disorders. Nutrients can act as the source of epigenetic modifications and can regulate the placement of these modifications. Nutrients involved in one-carbon metabolism, namely folate, vitamin B12, vitamin B6, riboflavin, methionine, choline and betaine, are involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S adenosylhomocysteine. Other nutrients and bioactive food components such as retinoic acid, resveratrol, curcumin, sulforaphane and tea polyphenols can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications. Aging and age-related diseases are associated with profound changes in epigenetic patterns, though it is not yet known whether these changes are programmatic or stochastic in nature. Future work in this field seeks to characterise the epigenetic pattern of healthy aging to ultimately identify nutritional measures to achieve this pattern. PMID- 22051145 TI - Electroporation improves the immune response induced by a DNA vaccine against pseudorabies virus glycoprotein B in pigs. AB - This study was performed to determine whether electroporation can be used to enhance the efficacy of a DNA vaccine against pseudorabies virus (PrV) in pigs. Immune responses to PrV were measured in pigs following a single intramuscular injection of plasmids encoding PrV glycoprotein B, with or without electroporation. Plasmid injection coupled with electroporation increased production of specific antibodies against PrV and peripheral blood mononuclear cells proliferated in response to stimulation with PrV glycoproteins. These results show that electroporation can improve the performance of a DNA vaccine against PrV in pigs. However, additional work is required to maximise the effectiveness of the vaccination protocol. PMID- 22051146 TI - Increased expression of CD146 and microvessel density (MVD) in invasive micropapillary carcinoma of the breast: Comparative study with invasive ductal carcinoma-not otherwise specified. AB - Invasive micropapillary carcinoma (IMPC) is a rare variant of ductal carcinoma of the breast, and is characterized by a high metastatic potential and an aggressive clinical course. Studies of CD146 expression and function in breast cancer remain scarce. The aim of this study was to evaluate the role of CD146 and microvessel density (MVD) in breast IMPC. CD146 mRNA expression and immunohistochemistry for CD146 and MVD measured by CD31 were assessed in 82 cases of IMPC and 137 cases of invasive ductal carcinoma, not otherwise specified (IDC-NOS). The mRNA level of CD146 in cancer specimens was higher in IMPC than in IDC-NOS. CD146 expression in tumor cells was up-regulated in IMPC as compared with that in IDC-NOS, and was positively correlated with histological grade, ER, PR status, and P53 expression in IMPC and IDC-NOS. CD146 expression in vascular endothelial cells was significantly higher than that in IDC, and was positively correlated with tumor progression in IMPC and IDC-NOS. MVD in IMPC was significantly higher than that in IDC. CD146 expression in tumor cells was positively correlated with that in vascular endothelial cells of IMPC and IDC-NOS. The association of CD146 expression with MVD and its correlation with progression in breast carcinoma indicated that CD146 is a potentially useful prognostic marker for breast cancer. CD146 could be a new drug target in the treatment of breast cancer. PMID- 22051147 TI - Toll-like receptor 2/MyD88 signaling mediates zymosan-induced joint hypernociception in mice: participation of TNF-alpha, IL-1beta and CXCL1/KC. AB - Arthritic pain is a serious health problem that affects a large number of patients. Toll-like receptors (TLRs) activation within the joints has been implicated in pathophysiology of arthritis. However, their role in the genesis of arthritic pain needs to be demonstrated. In the present study, it was addressed the participation of TLR2 and TLR4 and their adaptor molecule MyD88 in the genesis of joint hypernociception (a decrease in the nociceptive threshold) during zymosan-induced arthritis. Zymosan injected in the tibio-tarsal joint induced mechanical hypernociception in C57BL/6 wild type mice that was reduced in TLR2 and MyD88 null mice. On the other hand, zymosan-induced hypernociception was similar in C3H/HePas and C3H/HeJ mice (TLR4 mutant mice). Zymosan-induced joint hypernociception was also reduced in TNFR1 null mice and in mice treated with IL 1 receptor antagonist or with an antagonist of CXCR1/2. Moreover, the joint production of TNF-alpha, IL-1beta and CXCL1/KC by zymosan was dependent on TLR2/MyD88 signaling. Investigating the mechanisms by which TNF-alpha, IL-1beta and CXCL1/KC mediate joint hypernociception, joint administration of these cytokines produced mechanical hypernociception, and they act in an interdependent manner. In last instance, their hypernociceptive effects were dependent on the production of hypernociceptive mediators, prostaglandins and sympathetic amines. These results indicate that in zymosan-induced experimental arthritis, TLR2/MyD88 is involved in the cascade of events of joint hypernociception through a mechanism dependent on cytokines and chemokines production. Thus, TLR2/MyD88 signaling might be a target for the development of novel drugs to control pain in arthritis. PMID- 22051148 TI - GPR40-induced insulin secretion by the novel agonist TAK-875: first clinical findings in patients with type 2 diabetes. AB - AIM: Free fatty acids act as signalling molecules for modulating insulin secretion, and their insulinotropic effects are glucose-dependent and mediated through G protein-coupled receptor 40 (GPR40). This mechanism is a potential target for new treatments for managing diabetes. In this study, we present the first clinical data for TAK-875, a novel highly selective, orally bioavailable GPR40 agonist, in Japanese patients with type 2 diabetes insufficiently controlled by diet or exercise therapy. METHODS: This was an exploratory phase II, multicentre, randomized, double-blind, parallel group study comparing the efficacy and tolerability of TAK-875 100 and 400 mg, and placebo, all administered once daily for 2 weeks. RESULTS: After 2 weeks of treatment, TAK-875 produced marked glucose lowering effects in a 75 g oral glucose tolerance test (OGTT) as evidenced by mean +/- SE intergroup differences in plasma glucose AUC(0 3 h) of -12.98 +/- 1.48 (p < 0.0001) and -8.12 +/- 1.49 mmol.h/l (p < 0.0001), for TAK-875 400 mg vs. placebo and TAK-875 100 mg vs. placebo, respectively, and 2 h plasma glucose [-4.95 +/- 0.71 (p < 0.0001) and -3.21 +/- 0.71 mmol/l (p < 0.0001), respectively]. This was accompanied by a significant increase in insulin AUC(0-3 h) [34.68 +/- 12.16 (p < 0.01) and 31.49 +/- 12.20 (p < 0 . 05) uIU.h/ml, respectively]. Improvement in glycaemic profile was mirrored by a significant change in fasting plasma glucose [-2.37 +/- 0.27 (p < 0.0001) and -1.88 +/- 0.27 mmol/l (p < 0.0001), respectively]. No cases of hypoglycaemia were observed despite the significant reduction in plasma glucose. CONCLUSIONS: These exploratory findings provide evidence of the glucose-dependent insulinotropic potential of the GPR40 agonist TAK-875, and the promising clinical changes support future longer term clinical investigation. PMID- 22051149 TI - Ultrastructure features of camel cornea--collagen fibril and proteoglycans. AB - INTRODUCTION: The uniform distribution of collagen fibrils and proteoglycans maintain the transparency of normal cornea. We describe the ultrastructural features of camel cornea including collagen fibrils and proteoglycans (PGs). METHODS: Camel corneas (of 6-, 8-, and 10-month-old animals) were fixed in 2.5% glutaraldehyde containing cuprolinic blue in sodium acetate buffer and processed for electron microscopy. The 'AnalySIS LS Professional' program was used to analyze the collagen fibril diameter. RESULTS: The camel cornea consists of four layers: the epithelium (227 MUm), stroma (388 MUm), Descemet's membrane (DM), and endothelium. The epithelium constituted 36% of the camel cornea, whereas corneal stroma constituted 62% of the corneal thickness (629 MUm). The PGs in the posterior stroma were significantly larger in number and size compared with the anterior and middle stroma. The collagen fibril diameter was 25 nm and interfibrillar spacing 40 nm. Fibrillar structures are present throughout the DM. CONCLUSION: The structure of the camel cornea is very different from human and other animals. The unique structure of the cornea might be an adaptation to help the camel to survive in a hot and dry climate. The camel cornea may also be a good model to study the effect of hot and dry climates on the cornea. PMID- 22051150 TI - Function and evolution of 'green' GSK3/Shaggy-like kinases. AB - Glycogen synthase kinase 3 (GSK3) proteins, also known as SHAGGY-like kinases, have many important cell signalling roles in animals, fungi and amoebae. In particular, GSK3s participate in key developmental signalling pathways and also regulate the cytoskeleton. GSK3-encoding genes are also present in all land plants and in algae and protists, raising questions about possible ancestral functions in eukaryotes. Recent studies have revealed that plant GSK3 proteins are actively implicated in hormonal signalling networks during development as well as in biotic and abiotic stress responses. In this review, we outline the mechanisms of Arabidopsis GSK3 action, summarize GSK3 functions in dicot and monocot flowering plants, and speculate on the possible functions of GSK3s in the earliest-evolving land plants. PMID- 22051151 TI - Thermofluor-based optimization strategy for the stabilization and crystallization of Campylobacter jejuni desulforubrerythrin. AB - Desulforubrerythrin from Campylobacter jejuni has recently been biochemical and spectroscopically characterized. It is a member of the rubrerythrin family, and it is composed of three structural domains: the N-terminal desulforedoxin domain with a non-heme iron center, followed by a four-helix bundle domain harboring a binuclear iron center and finally a C-terminal rubredoxin domain. To date, this is the first example of a protein presenting this kind of structural domain organization, and therefore the determination of its crystal structure may unveil unexpected structural features. Several attempts were made in order to obtain protein crystals, but always without success. As part of our strategy the thermofluor method was used to increase protein stability and its propensity to crystallize. This approach has been recently used to optimize protein buffer formulation, thus yielding more stable and homogenous protein samples. Thermofluor has also been used to identify cofactors/ligands or small molecules that may help stabilize native protein states. A successful thermofluor approach was used to select a pH buffer condition that allowed the crystallization of Campylobacter jejuni desulforubrerythrin, by screening both buffer pH and salt concentration. A buffer formulation was obtained which increased the protein melting temperature by 7 degrees C relatively to the initial purification buffer. Desulforubrerythrin was seen to be stabilized by lower pH and high salt concentration, and was dialyzed into the new selected buffer, 100mM MES pH 6.2, 500mM NaCl. This stability study was complemented with a second thermofluor assay in which different additives were screened. A crystallization screening was carried out and protein crystals were rapidly obtained in one condition. Protein crystal optimization was done using the same additive screening. Interestingly, a correlation between the stability studies and crystallization experiments using the additive screening could be established. The work presented here shows an elegant example where thermofluor was shown to be a key biophysical method that allowed the identification of an improved buffer formulation and the applicability of this technique to increase the propensity of a protein to crystallize is discussed. PMID- 22051152 TI - [A new opportunity to continue to grow]. PMID- 22051153 TI - Effects of vildagliptin on postprandial markers of bone resorption and calcium homeostasis in recently diagnosed, well-controlled type 2 diabetes patients. AB - BACKGROUND: Bone metabolism is a dynamic process that is influenced by food ingestion. Endogenous incretins have been shown to be important regulators of bone turnover. The aim of the present study was to assess whether a dipeptidylpeptidase (DPP)-4 inhibitor affects markers of bone resorption and calcium homeostasis. METHODS: The present study was a single-center, double blind, randomized clinical trail. Fifty-nine drug-naive patients with type 2 diabetes (T2D) were randomized to either 1 year treatment with the DPP-4 inhibitor vildagliptin (100 mg, once daily; n = 29) or placebo (n = 30). Patients received a standardized breakfast after measurement of serum concentrations of cross-linked C-terminal telopeptide (s-CTx), a bone resorption marker influenced by food intake, before and after 50 weeks treatment. RESULTS: Vildagliptin did not change postprandial s-CTx concentrations compared with pretreatment levels (between-group ratio 1.15 +/- 0.17; P = 0.320). Fasting serum alkaline phosphatase, calcium, and phosphate were also unaffected y 1 year treatment with vildagliptin. CONCLUSIONS: Treatment with vildagliptin for 1 year was not associated with changes in markers of bone resorption and calcium homeostasis in drug-naive patients with T2D and mild hyperglycemia. PMID- 22051154 TI - Microbes and mass extinctions: paleoenvironmental distribution of microbialites during times of biotic crisis. AB - Widespread development of microbialites characterizes the substrate and ecological response during the aftermath of two of the 'big five' mass extinctions of the Phanerozoic. This study reviews the microbial response recorded by macroscopic microbial structures to these events to examine how extinction mechanism may be linked to the style of microbialite development. Two main styles of response are recognized: (i) the expansion of microbialites into environments not previously occupied during the pre-extinction interval and (ii) increases in microbialite abundance and attainment of ecological dominance within environments occupied prior to the extinction. The Late Devonian biotic crisis contributed toward the decimation of platform margin reef taxa and was followed by increases in microbialite abundance in Famennian and earliest Carboniferous platform interior, margin, and slope settings. The end-Permian event records the suppression of infaunal activity and an elimination of metazoan-dominated reefs. The aftermath of this mass extinction is characterized by the expansion of microbialites into new environments including offshore and nearshore ramp, platform interior, and slope settings. The mass extinctions at the end of the Triassic and Cretaceous have not yet been associated with a macroscopic microbial response, although one has been suggested for the end-Ordovician event. The case for microbialites behaving as 'disaster forms' in the aftermath of mass extinctions accurately describes the response following the Late Devonian and end Permian events, and this may be because each is marked by the reduction of reef communities in addition to a suppression of bioturbation related to the development of shallow-water anoxia. PMID- 22051156 TI - Quantified tracking and monitoring of diazepam treated socially housed cynomolgus monkeys. AB - Quantitative assessment of behavioural patterns is frequently used in rodent toxicity studies, however only limited approaches are available for monkeys. Often qualitative behavioural scoring using functional observation batteries (FOBs) is performed, with difficulties like poor reproducibility or lack of sensitivity. In this study, we investigated whether quantitative behavioural monitoring can be applied to group-housed cynomolgus monkeys. Video-tracking EthoVision(r) XT system and special analysis software were used to evaluate diazepam (i.v. 1mg/kg) related behavioural changes in group-housed animals. Recordings were made predose and at the anticipated time of maximum drug exposure (T(max)). General parameters such as distance travelled and velocity did not reveal the known sedative effects of diazepam. However, inspection of the automatically generated track images indicated that diazepam-treated animals had more a meandering movement pattern suggesting that diazepam induced a loss of balance which was regained by corrective movements. Therefore, parameters revealing specific aspects of the meandering movement pattern such as velocity profiles and turn angles have been analyzed and revealed an increase in the curvature and in the number of directional changes of the movement path. PMID- 22051155 TI - Investigation by site-directed mutagenesis of the role of cytochrome P450 2B4 non active-site residues in protein-ligand interactions based on crystal structures of the ligand-bound enzyme. AB - Residues located outside the active site of cytochromes P450 2B have exhibited importance in ligand binding, structural stability and drug metabolism. However, contributions of non-active-site residues to the plasticity of these enzymes are not known. Thus, a systematic investigation was undertaken of unique residue residue interactions found in crystal structures of P450 2B4 in complex with 4-(4 chlorophenyl)imidazole (4-CPI), a closed conformation, or in complex with bifonazole, an expanded conformation. Nineteen mutants distributed over 11 sites were constructed, expressed in Escherichia coli and purified. Most mutants showed significantly decreased expression, especially in the case of interactions found in the 4-CPI structure. Six mutants (H172A, H172F, H172Q, L437A, E474D and E474Q) were chosen for detailed functional analysis. Among these, the K(s) of H172F for bifonazole was ~ 20 times higher than for wild-type 2B4, and the K(s) of L437A for 4-CPI was ~ 50 times higher than for wild-type, leading to significantly altered inhibitor selectivity. Enzyme function was tested with the substrates 7 ethoxy-4-(trifluoromethyl)coumarin, 7-methoxy-4-(trifluoromethyl)coumarin and 7 benzyloxyresorufin (7-BR). H172F was inactive with all three substrates, and L437A did not turn over 7-BR. Furthermore, H172A, H172Q, E474D and E474Q showed large changes in k(cat)/K(M) for each of the three substrates, in some cases up to 50-fold. Concurrent molecular dynamics simulations yielded distances between some of the residues in these putative interaction pairs that are not consistent with contact. The results indicate that small changes in the protein scaffold lead to large differences in solution behavior and enzyme function. PMID- 22051157 TI - Role of iodine in diiodomethyl-p-tolylsulfone induced reproductive toxicity in rats: proposed mode of action. AB - The biocide diiodomethyl-p-tolylsulfone (DIMPTS) caused dystocia, decreased neonatal survival and hypothyroidism in rat reproduction studies resembling the effects caused by iodine. One molecule of DIMPTS contains two iodine moieties that are hydrolyzed upon ingestion and systemically absorbed, suggesting iodine toxicity as a probable mode of action for the effects observed in rats. This study compared the effects induced by DIMPTS and an equimolar concentration of its de-iodinated analogue, methyl-p-tolylsulfone (MPTS). Groups of 20 female Sprague Dawley rats were fed diets supplying 80 mg DIMPTS/kg/day, 32 mg MPTS/kg/day or control feed from prior to breeding through lactation and gonadal function, mating performance, conception, gestation, parturition, lactation, survival, growth and development of pups evaluated through postnatal day 7. Serum thyroid hormones and iodine levels in milk and sera were also determined. Females given DIMPTS had increased incidence of vulvar discharge and dystocia, decreased litter size, decreased body weights and feed consumption, increased thyroid weights, thyroid follicular cell hypertrophy with decreased colloid, decreased triidothyronine, and increased thyroid stimulating hormone levels. DIMPTS pups had decreased neonatal survival and body weights. These effects were associated with elevated levels of iodine in milk and sera. In contrast, MPTS did not produce similar effects in adult females or their offspring. These data support the hypothesis that the dystocia, altered neonatal survival and hypothyroidism following repeated dietary administration of DIMPTS were due to excessive iodine released from DIMPTS during absorption and metabolism. PMID- 22051158 TI - Src family kinases: modulators of neurotransmitter receptor function and behavior. AB - Src family kinases (SFKs) are non-receptor-type protein tyrosine kinases that were originally identified as the products of proto-oncogenes and were subsequently implicated in the regulation of cell proliferation and differentiation in the developing mammalian brain. Recent studies using transgenic mouse models have demonstrated that SFKs that are highly expressed in the adult brain regulate neuronal plasticity and behavior through tyrosine phosphorylation of key substrates such as neurotransmitter receptors. Here, we provide an overview of these recent studies, as well as discussing how modulation of the endocytosis of neurotransmitter receptors by SFKs contributes, in part, to this regulation. Deregulation of SFK-dependent tyrosine phosphorylation of such substrates might underlie certain brain disorders. PMID- 22051159 TI - In vitro antibacterial activity of different endodontic irrigants. AB - AIM: The objective of this study was to compare in vitro the antibacterial activity of Tetraclean (mixture of doxycycline, citric acid and polypropylene glycol), Niclor 5 (5.25% sodium hypochlorite solution), Cloreximid (0.2% chlorhexidine and 0.2% cetrimide solution) and hydrogen peroxide 12 volumes on three endodontic pathogens associated with primary endodontic infections. Enterococcus faecalis, Streptococcus mutans and Staphylococcus aureus strains were selected to evaluate the antibacterial activity of endodontic irrigants by the agar disc-diffusion test. MATERIAL AND METHODS: Paper discs were saturated with each one of the test solutions (at room temperature and preheating at 50 degrees C) and placed onto culture agar-plates preadsorbed with bacterial cells and further incubated for 24 h at 37 degrees C. The growth inhibition zones around each irrigant were recorded and compared for each bacterial strain. Kruskal-Wallis and Mann-Whitney tests were applied to compare the various groups. RESULTS: At room temperature, Tetraclean showed significantly higher inhibition of bacteria growth than all other irrigants tested. Preheating at 50 degrees C significantly increased growth inhibition for all the groups tested. At 50 degrees C, hydrogen peroxide 12 volumes and Tetraclean showed significantly higher efficacy than all other irrigants tested. CONCLUSIONS: 50 degrees C preheated hydrogen peroxide 12 volumes and Tetraclean showed highest inhibition of the bacterial growth. PMID- 22051160 TI - Characteristics of autism spectrum disorders in a sample of egyptian and saudi patients: transcultural cross sectional study. AB - BACKGROUND: Autism is a biological disorder with clearly defined phenomenology. Studies from the Middle East on this topic have been particularly rare. Little is known about the influence of culture on clinical features, presentations and management of autism. The current study was done to compare characteristics of autism in two groups of Egyptian as well as Saudi children. METHODS: The sample included 48 children with Autism Spectrum Disorder. They were recruited from the Okasha Institute of Psychiatry, Ain Shams University, Cairo, Egypt and Al-Amal Complex for Mental Health, Dammam, Kingdom of Saudi Arabia. They were grouped into an Egyptian group (n = 20) and a Saudi group (n = 28). They were assessed both clinically and psychometrically using the GARS, the Vineland adaptive behavioral scale, and the Stanford Binnet IQ test. RESULTS: Typical autism was more prevalent than atypical autism in both groups. There were no statistically significant differences in clinical variables like regression, hyperactivity, epilepsy or mental retardation. Delayed language development was significantly higher in the Egyptian group while delay in all developmental milestones was more significant in the Saudi group. The Vineland communication subscale showed more significant severe and profound communication defects in the Saudi group while the Gilliam developmental subscale showed significantly more average scores in the Egyptian group. Both groups differed significantly such that the age of noticing abnormality was younger in the Saudi group. The age at diagnosis and at the commencement of intervention was lower in the Egyptian group. The Saudi group showed a higher percentage of missing examinations, older birth order and significantly higher preference to drug treatment, while the Egyptian group showed a high preference to behavioral and phoniatric therapies, higher paternal and maternal education, higher employment among parents and higher family concern. CONCLUSION: Cultural context may significantly influence the age of noticing abnormality, the age of starting intervention, developmental and perinatal problems, family concerns about managing the problem as well as familial tendency for neurodevelopmental disorders, all of which have important impact on clinical symptomatology and severity of autism. Culture also influences significantly the ways of investigating and treating autism. PMID- 22051162 TI - Comparisons of the effects of 12-week administration of miglitol and voglibose on the responses of plasma incretins after a mixed meal in Japanese type 2 diabetic patients. AB - To compare the effects of miglitol [an alpha-glucosidase inhibitor (AGI) absorbed in the intestine] and voglibose (an AGI not absorbed) on plasma glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels, 26 and 24 Japanese type 2 diabetic patients were randomly assigned to receive miglitol or voglibose, respectively. After 12-week administration of both drugs, during 2-h meal tolerance test, plasma glucose, serum insulin and total GIP were significantly decreased and active GLP-1 was significantly increased. Miglitol group showed a significantly lower total GIP level than voglibose group. Miglitol, but not voglibose, significantly reduced body weight (BW). In all participants, the relative change in BW was positively correlated with that of insulin significantly and of GIP with a weak tendency, but not of GLP-1. In conclusion, both drugs can enhance postprandial GLP-1 responses and reduce GIP responses. The significant BW reduction by miglitol might be attributable to its strong GIP-reducing efficacy. PMID- 22051161 TI - Non-blood medical care in gynecologic oncology: a review and update of blood conservation management schemes. AB - This review attempts to outline the alternative measures and interventions used in bloodless surgery in the field of gynecologic oncology and demonstrate their effectiveness. Nowadays, as increasingly more patients are expressing their fears concerning the potential risks accompanying allogenic transfusion of blood products, putting the theory of bloodless surgery into practice seems to gaining greater acceptance. An increasing number of institutions appear to be successfully adopting approaches that minimize blood usage for all patients treated for gynecologic malignancies. Preoperative, intraoperative and postoperative measures are required, such as optimization of red blood cell mass, adequate preoperative plan and invasive hemostatic procedures, assisting anesthetic techniques, individualization of anemia tolerance, autologous blood donation, normovolemic hemodilution, intraoperative cell salvage and pharmacologic agents for controlling blood loss. An individualised management plan of experienced personnel adopting a multidisciplinary team approach should be available to establish non-blood management strategies, and not only on demand of the patient, in the field of gynecologic oncology with the use of drugs, devices and surgical-medical techniques. PMID- 22051163 TI - Immunohistochemical evaluation of fibrovascular and cellular pre-iridal membranes in dogs. AB - OBJECTIVE: Histologically, two morphologically distinct types of pre-iridal membranes appear to occur in diseased canine globes: fibrovascular and cellular. Cellular pre-iridal membranes of corneal endothelial origin exist in iridocorneal endothelial (ICE) syndrome in humans and arise through metaplastic transformation of corneal endothelial cells into epithelial-like cells.(1) The purpose of this study was to (i) evaluate immunohistochemical staining of these two types of membranes in diseased canine globes, (ii) determine whether endothelial cell metaplasia or iridal vascular budding plays a role in cellular membrane formation and (iii) compare the primary histopathologic diagnosis between the two groups. PROCEDURES: Hematoxylin and eosin (H&E)-stained slides of 28 enucleated canine specimens with pre-iridal membranes were randomly selected and examined with light microscopy. The globes were divided into two groups based on the appearance of the membrane: fibrovascular or cellular, and the histopathologic diagnoses were recorded. Immunohistochemical staining for vimentin, cytokeratin AE1/AE3, and Von Willebrand's factor (Factor VIII) was completed on the slides of each globe. The histopathologic diagnoses were compared between the two groups. RESULTS: The fibrovascular and cellular membranes stained positive for vimentin and negative for cytokeratin AE1/AE3. All fibrovascular membranes stained positive for Factor VIII compared with the cellular membranes which stained negative. In the cellular membrane group, primary glaucoma was a common histologic diagnosis. CONCLUSIONS: Immunohistochemical evaluation in this study does not support the hypothesis of metaplastic transformation of endothelial cells into epithelial-like cells in the canine globes with cellular membranes. The cellular membranes in this study do not represent a canine version of ICE syndrome and are not of vascular endothelial origin. PMID- 22051165 TI - Regenerative medicine. PMID- 22051164 TI - GnRH receptor activation competes at a low level with growth signaling in stably transfected human breast cell lines. AB - BACKGROUND: Gonadotrophin releasing hormone (GnRH) analogs lower estrogen levels in pre-menopausal breast cancer patients. GnRH receptor (GnRH-R) activation also directly inhibits the growth of certain cells. The applicability of GnRH anti proliferation to breast cancer was therefore analyzed. METHODS: GnRH-R expression in 298 primary breast cancer samples was measured by quantitative immunofluorescence. Levels of functional GnRH-R in breast-derived cell lines were assessed using 125I-ligand binding and stimulation of 3H-inositol phosphate production. Elevated levels of GnRH-R were stably expressed in cells by transfection. Effects of receptor activation on in vitro cell growth were investigated in comparison with IGF-I and EGF receptor inhibition, and correlated with intracellular signaling using western blotting. RESULTS: GnRH-R immunoscoring was highest in hormone receptor (triple) negative and grade 3 breast tumors. However prior to transfection, functional endogenous GnRH-R were undetectable in four commonly studied breast cancer cell lines (MCF-7, ZR-75-1, T47D and MDA-MB-231). After transfection with GnRH-R, high levels of cell surface GnRH-R were detected in SVCT and MDA-MB-231 clones while low-moderate levels of GnRH-R occurred in MCF-7 clones and ZR-75-1 clones. MCF-7 sub-clones with high levels of GnRH-R were isolated following hygromycin phosphotransferase transfection. High level cell surface GnRH-R enabled induction of high levels of 3H-inositol phosphate and modest growth-inhibition in SVCT cells. In contrast, growth of MCF-7, ZR-75-1 or MDA-MB-231 clones was unaffected by GnRH-R activation. Cell growth was inhibited by IGF-I or EGF receptor inhibitors. IGF-I receptor inhibitor lowered levels of p-ERK1/2 in MCF-7 clones. Washout of IGF-I receptor inhibitor resulted in transient hyper-elevation of p-ERK1/2, but co addition of GnRH-R agonist did not alter the dynamics of ERK1/2 re phosphorylation. CONCLUSIONS: Breast cancers exhibit a range of GnRH-R immunostaining, with higher levels of expression found in triple-negative and grade 3 cancers. However, functional cell surface receptors are rare in cultured cells. Intense GnRH-R signaling in transfected breast cancer cells did not markedly inhibit growth, in contrast to transfected HEK 293 cells indicating the importance of intracellular context. GnRH-R signaling could not counteract IGF-I receptor-tyrosine kinase addiction in MCF-7 cells. These results suggest that combinatorial strategies with growth factor inhibitors will be needed to enhance GnRH anti-proliferative effects in breast cancer. PMID- 22051166 TI - Chemical-physical properties and in vitro cell culturing of a novel biphasic bio mimetic scaffold for osteo-chondral tissue regeneration. AB - The requirements for a successful regeneration of an osteo-chondral defect could effectively be met by using a bi-layered composite scaffold, able to support proliferation and differentiation of mesenchymal stem cells, while providing a biochemical environment promoting the formations of the two distinct tissues. The novel strategy here presented consists of developing a bio-mimetic scaffolds obtained by the combination of two integrated organic compounds (type I collagen and chitosan) with or without bioactive Mg-doped hydroxyapatite (Mg-HA) nanocrystals, depending on the specific layer, reproducing cartilaginous or subchondral bone tissue. An innovative patented methodology for scaffolds production, called - pH-dependent 3-phasic assembling -, allowed to development of a highly homogenous and chemically stable scaffold, presenting a very good integration among all three components, as confirmed by extensive SEM and thermogravimetric analyses. A preliminary in vitro evaluation was also carried out by seeding bi-layered scaffold with human bone marrow stromal cells (h-MSCs), by giving particular emphasis to cell viability and distribution at day 0, 7 and 14. Cells were viable and uniformly colonized the whole scaffold until day 14, indicating that the scaffold contributed to the maintenance of cell behaviour. PMID- 22051167 TI - Electrically conductive surface modifications of three-dimensional polypropylene fumarate scaffolds. AB - Polypropylene fumarate (PPF) scaffolds fabricated by rapid prototyping were surface modified by solution deposition of electrically conductive polypyrrole coatings with or without hydroxyapatite. Scaffolds were electrically conductive with resistivity as low as 2Omega. Scaffold characterization by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and thermo gravimetric analysis shows both polypyrrole and hydroxyapatite are present. Cell viability, attachment, proliferation, and differentiation were analyzed using human fetal osteoblast cells. These studies show that surface modification using hydroxyapatite improved cell attachment and proliferation of osteoblasts onto the PPF scaffolds. Alkaline phosphatase activity as a marker for osteogenic differentiation of cell to mature osteoblasts was analyzed. Our data reveal that osteoblasts maintained their phenotype on PPF scaffolds with and without coatings. Thus, these scaffolds could be appropriate candidates for our future in vivo studies. PMID- 22051168 TI - Reversine increases multipotent human mesenchymal cells differentiation potential. AB - Among different human stem cell sources, adult mesenchymal stem cells from bone marrow (BMSCs), and more recently from adipose tissues (ASCs), have shown their capability to differentiate into a variety of different cell types, including osteoblasts, adipocytes, and muscle cells. However, mesenchymal stem cell differentiation toward certain cell types (including skeletal and cardiac muscle), while shown to be achievable, still suffers of low yields and needs to be greatly improved before any therapeutic application could be foreseen. A possible way of achieving this goal is by using a chemical-pharmacological approach to increase stem cell plasticity. Along this line, we envisioned the possibility of pre-treating BMSCs and ASCs with reversine, a synthetic purine that has been shown to induce adult cells de-differentiation. In the current study we tested reversine effects on both BMSCs and ASCs to increase their differentiation toward osteoblasts, smooth and skeletal muscle cells. Reversine pre-treatment, at very low concentration (50 nM), caused a marked increase in the differentiation yields of both BMSCs and ASCs. PMID- 22051169 TI - Enhanced biological performance of human adipose-derived stem cells cultured on titanium-based biomaterials and silicon carbide sheets for orthopaedic applications. AB - It is well known that the surface properties of biomaterials may affect bone healing processes by modulating both cell viability and osteogenic differentiation. In this study we evaluated proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs) cultured on three prototypes of titanium disks and on thin layers of silicon carbide (SiC-PECVD), a material characterized by a high hardness and wear resistance. Our data indicated that all the tested surfaces supported cell growth, in particular, hASCs seeded on both titanium treated by a double-step etching process (TIT) and titanium modified by two Anodic Spark Deposition processes (TAA) grew better respect to the ones cultured on titanium obtained by KOH alkali etching process on TAA (TAAK). Furthermore, hASCs well colonized SiC-PECVD surface, showing a quite similar viability to cells cultured on plastic (PA). TIT and TAA better supported osteogenic differentiation of hASCs compared to PA, as shown by a marked increase of both alkaline phosphatase activity and calcified extracellular matrix deposition; in contrast TAAK did not positively affect hASCs differentiation. SiC PECVD did not alter osteogenic differentiation of hASC cells: indeed, ALP and calcium deposition levels were comparable to those of cells cultured on plastic. Furthermore, we observed similar results testing hASCs either pre-differentiated for 14 days in osteogenic medium or directly differentiated on biomaterials. Our study suggests that modifications of titanium surface may improve osteo integration of implant devices and that SiC-PECVD may represent a valid alternative for the coating of prosthetic devices to reduce wear and metallosis events. PMID- 22051170 TI - Thrombin and thrombin-derived peptides promote proliferation of cardiac progenitor cells in the form of cardiospheres without affecting their differentiation potential. AB - Many studies demonstrated that human adult cardiac progenitor cells in the form of cardiospheres (CSps) could represent a powerful candidate for cardiac cell therapy. To achieve the clinical translation of this biotechnological product, the development of well-defined culture conditions is required to optimize their proliferation and differentiation. Thrombin, a serine protease acting through the protease-activated receptor 1 (PAR-1) signalling to modulate many cellular functions such as proliferation and differentiation in several cell types, is one of the factors included in the CSps medium. Therefore, the assessment of the effective dependence of the thrombin related cellular effects from PAR-signalling is strategic both for understanding the biological potential of these cells and for the GMP translation of the medium formulation, using synthesised analogs. In this study the effects of thrombin on human CSps and their potential relationship with the specific proteolytic activation of PAR-1 have been investigated in different culture conditions, including thrombin inhibitor hirudin and PAR-1 agonist/ antagonist peptides TFLLR and MUMB2. In this study we show that, in the presence of thrombin and TFLLR, CSps, in which PAR-1 expression was evidenced by immunofluorescence and western blot analysis, increase their proliferation activity (BrdU assay). Such increased proliferative rate was consistently associated with a higher phosphorylation level of the cell cycle inhibitor GSK3. Concerning the assessment of the potential effects of thrombin and its agonist on differentiation, both western blot and real-time PCR analysis for stemness, cardiac and vascular markers (such as cKit, cx43 and KDR) showed that CSps commitment was substantially unaffected, except for GATA4 mRNA, whose transcription was down-regulated in the presence of the natural protease, but not after treatment with TFLLR. In conclusion, activation of PAR-1-dependent signalling is important to support CSps proliferative potential, keeping unaltered or at best stable their differentiation properties. The availability of thrombin agonists, such as TFLLR, able to guarantee the required growth effect without affecting CSps lineage commitment, could represent a technological improvement for cost-effective, easy-to-handle and GMPtranslatable synthetic media. PMID- 22051171 TI - Evaluation of chondrocyte behavior in a new equine collagen scaffold useful for cartilage repair. AB - Association of biomaterials with autologous cells can provide a new generation of implantable devices for cartilage repair. An ideal scaffold should possess a preformed three-dimensional shape, fix the cells to the damaged area and prevent their migration into the articular cavity. Furthermore, the constructs should have sufficient mechanical strength to facilitate handling in a clinical setting and stimulate the uniform spreading of cells and a phenotype re-differentiation process. The aim of this study was to verify the ability of an equine collagen membrane to support the growth of human chondrocytes and to allow the re expression of their original phenotype. This ability was assessed by the evaluation of collagen type I, II and aggrecan mRNA expression by Real-Time PCR. Immunohistochemical analyses were performed to evaluate collagen type I, II and proteoglycans synthesis. Electron microscopy was utilized to highlight the structure of the biomaterial and its interactions with the cells. Our data indicate that human chondrocytes seeded onto a collagen membrane express and produce collagen type II and aggrecan and downregulate the production of collagen type I during the experimental times analyzed. These results provide an in vitro demonstration for the therapeutic potential of autologous chondrocyte transplantation by an equine collagen membrane as a delivery vehicle in a tissue engineered approach towards the repair of articular cartilage defects. PMID- 22051172 TI - Biodegradable microcarriers as cell delivery vehicle for in vivo transplantation and magnetic resonance monitoring. AB - Microcarrier culture systems offer an attractive method for cell amplification and as delivery vehicle. At the same time, super paramagnetic iron oxide (SPIO) nanoparticles represent a unique in vivo tracking system, already approved for clinical use. In our study, we tested the combination of clinically approved microcarriers and SPIO nanoparticles for cell-construct delivery and subsequent tracking after implantation. In order to mimic better a clinical setting, biodegradable macroporous microcarriers were employed as an alternative approach to expand human primary chondrocytes in a dynamic culture system for subsequent direct transplantation. In addition, cellseeded microcarriers were labeled with SPIO nanoparticles to evaluate the benefits of cell-constructs tracking with magnetic resonance. In vivo subcutaneous implants were monitored for up to 3 weeks and orthotopic implantation was simulated and monitored in ex vivo osteochondral defects. PMID- 22051173 TI - Characterization and differentiation of equine tendon-derived progenitor cells. AB - Mesenchymal stem cells have been recently investigated for their potential use in regenerative medicine. Population of adult stem cells were recently identified in human and lab animal tendons, but no detailed investigations have been made in the equine species. The aim of our study is to identify a progenitor cell population from tendon tissue (TSPCs) in the horse superficial digital flexor tendon that are able to be highly clonogenic, to grow fast and to differentiate in different induced cell lineages as well as bone marrow derived progenitor cells (BM-MSCs). The hypothesis that TSPCs possess a mesenchymal stem cell behavior opens a new prospective for tendon regenerative medicine approaches. TSPCs were expanded more rapidly and showed higher plating efficiency when compared with BM-MSCs. Both cell lines expressed identical stem cell markers in vitro and they were able to differentiate towards osteogenic and adipogenic lineages as demonstrated with cytochemical staining and mRNA gene expression. TSPCs showed a positive but limited chondrogenic differentiation compared with BM MSCs as demonstrated by histological and biochemical analyses. According to our results, equine TSPCs have high clonogenic properties and proliferating potential, they express stem cell markers and have the capability to be multipotent as well as BM-MSCs. These findings suggest that TSPCs may represent a good model for stem cell biology and could be useful for future tendon regenerative medicine investigations. PMID- 22051174 TI - Effects of cognitive therapy versus interpersonal psychotherapy in patients with major depressive disorder: a systematic review of randomized clinical trials with meta-analyses and trial sequential analyses. AB - BACKGROUND: Major depressive disorder afflicts an estimated 17% of individuals during their lifetime at tremendous suffering and cost. Cognitive therapy and interpersonal psychotherapy are treatment options, but their effects have only been limitedly compared in systematic reviews. METHOD: Using Cochrane systematic review methodology we compared the benefits and harm of cognitive therapy versus interpersonal psychotherapy for major depressive disorder. Trials were identified by searching the Cochrane Library's CENTRAL, Medline via PubMed, EMBASE, Psychlit, PsycInfo, and Science Citation Index Expanded until February 2010. Continuous outcome measures were assessed by mean difference and dichotomous outcomes by odds ratio. We conducted trial sequential analysis to control for random errors. RESULTS: We included seven trials randomizing 741 participants. All trials had high risk of bias. Meta-analysis of the four trials reporting data at cessation of treatment on the Hamilton Rating Scale for Depression showed no significant difference between the two interventions [mean difference -1.02, 95% confidence interval (CI) -2.35 to 0.32]. Meta-analysis of the five trials reporting data at cessation of treatment on the Beck Depression Inventory showed comparable results (mean difference -1.29, 95% CI -2.73 to 0.14). Trial sequential analysis indicated that more data are needed to definitively settle the question of a differential effect. None of the included trial reported on adverse events. CONCLUSIONS: Randomized trials with low risk of bias and low risk of random errors are needed, although the effects of cognitive therapy and interpersonal psychotherapy do not seem to differ significantly regarding depressive symptoms. Future trials should report on adverse events. PMID- 22051175 TI - Prevalence of protozoa, viruses, coliphages and indicator bacteria in groundwater and river water in the Kathmandu Valley, Nepal. AB - Limited information is available on the prevalence of waterborne pathogens in aquatic environments in developing countries. In this study, water samples were collected from nine shallow wells and a river in the Kathmandu Valley, Nepal, during the rainy season in 2009 and were subjected to detection of waterborne protozoa, viruses and coliphages using a recently developed method for simultaneous concentration of protozoa and viruses in water. Escherichia coli and total coliforms were also tested as indicator bacteria. At least one type of the five pathogens tested (Cryptosporidium, Giardia, human adenoviruses, and noroviruses of genogroups I and II) was detected in five groundwater samples (56%) (1000 ml each) from shallow wells. Compared with groundwater samples, the pathogens were more abundant in the river water sample (100ml); the concentrations of Cryptosporidium and Giardia were 140 oocysts/l and 8500 cysts/l, respectively, and the mean threshold cycle (Ct) values in real-time RT PCR were 34.3, 36.8 and 34.0 for human adenoviruses and noroviruses of genogroups I and II, respectively. Genotyping of F-RNA coliphages by real-time RT-PCR was successfully used to differentiate human and animal faecal contamination in the samples. Moreover, for the groundwater samples, protozoa and viruses were detected only in E. coli-positive samples, suggesting that E. coli may be an appropriate indicator of pathogen contamination of valley groundwater. PMID- 22051176 TI - Maternal hypertension during pregnancy modifies the response of the immature brain to hypoxia-ischemia: sequential MRI and behavioral investigations. AB - Hypoxic-ischemic (HI) brain injury occurring during the perinatal period is still a major cause of mortality and morbidity. We assessed the impact of maternal hypertension, the most common medical disorder of pregnancy, on the anatomical and functional consequences of HI insult in the immature brain. Rat pups from spontaneously hypertensive (SHR) and normotensive (Wistar Kyoto - WKY) dams were subjected to HI brain damage at post-natal day 7 (P7). Brain lesion and functional deficits were analyzed from 10 min to 35 days after HI, using magnetic resonance imaging (MRI), sensorimotor and cognitive tests. MRI data revealed that SHR pups displayed less brain damage than WKY, attested by an initial smaller lesion followed by a reduced tissue loss at chronic stage (57.1+/-21.6 and 31.1+/ 27% ipsilateral hemisphere atrophy in WKY and SHR, respectively). Behavioral analyses showed less HI-induced behavioral deficits in motor coordination (rotarod test) and spatial learning (Morris water maze test) in pups from hypertensive dams compared to those from normotensive ones. The data suggest that maternal hypertension causes prenatal stress that may render the immature brain more resistant to subsequent hypoxia-ischemia, related to a preconditioning phenomenon. PMID- 22051177 TI - Eosinophilic keratoconjunctivitis in two rabbits. AB - The purpose of this case report is to describe the clinical course and cytologic findings, treatment, and outcome of eosinophilic keratoconjunctivitis in two rabbits. Ophthalmic examination revealed ocular discharge, dacryocystitis, blepharitis, conjunctivitis, white conjunctival and corneal plaques, corneal vascularization, and stromal infiltration with different degrees of severity in each case. In case 2 there was also ulcerative disease of the cornea. Computerized tomography scan of the head, corneal biopsy for histopathologic examination with additional Luna and Giemsa stain were performed in case 2 and conjunctival as well as corneal specimens were obtained for bacteriologic culture and cytologic examination in case 1. Based on test results, a diagnosis of eosinophilic keratoconjunctivitis was made in case 2 and a tentative diagnosis of eosinophilic keratoconjunctivitis was made in case 1. Response to treatment with a topical steroid and topical cyclosporin was supportive of the diagnosis in both cases and shared many similarities with the response to treatment previously described in cats. Eosinophilic keratitis should be considered as part of a differential diagnosis list in rabbits with a history of keratitis. PMID- 22051178 TI - Silent sinus syndrome. AB - Silent sinus syndrome is defined as a spontaneous and progressive enophthalmos and hypoglobus with hypoplasia of the maxillary sinus and resorption of the orbital floor. It is caused by atelectasis of the maxillary sinus in the presence of ipsilateral chronic hypoventilation of the sinus. The problem may be idiopathic, but the term is now also used to describe cases that follow operation or trauma. We describe three cases, each with a different aetiology, and discuss the clinical and radiographic evaluation of the condition, theories regarding its pathophysiology, and surgical correction. PMID- 22051179 TI - An experimental study of the management of severe keratoconjunctivitis sicca with autologous reduced-sized submandibular gland transplantation. AB - We have evaluated transplantation of reduced submandibular glands for the treatment of severe keratoconjunctivitis sicca. Thirty-four rabbits were allocated into three groups: dry eye (controls, n=10), transplantation of whole submandibular glands (n=12), and transplantation of reduced submandibular glands (n=12). Outcome measures included the results of Schirmer's test and the Rose Bengal test, and histological examination of the cornea and the transplanted gland. Volume of tears significantly increased after transplantation of the whole gland, but did not change after transplantation of the reduced gland compared with dry eyes induced preoperatively. Neither transplantion group had keratoconjunctivitis sicca postoperatively. There were no histological abnormalities in the transplanted tissues. The results that the surgical technique of using reduced submandibular glands for transplantation was feasible, and that the secretion from the reduced gland was similar to that from a normal lacrimal gland. In conclusion, transplantation of a reduced submandibular glands is feasible in the treatment of keratoconjunctivitis sicca. PMID- 22051180 TI - Morphological characterization and functional immune response of the carpet shell clam (Ruditapes decussatus) haemocytes after bacterial stimulation. AB - The morphology and functionality of Ruditapes decussatus haemocytes have been characterized by light microscopy and flow cytometry, leading to the identification of three different cellular subpopulations. Granulocytes were the largest cells, the hyalinocytes were smaller and contained fewer granules and the intermediate cells showed a size similar to hyalinocytes and a higher number of granules. The phagocytosis of different particles and the associated production of oxygen radicals were measured by flow cytometric methods. Granulocytes were the most active cells, followed by the intermediate cells and hyalinocytes. The effect of stimulation of haemocytes with lipopolysaccharide (LPS), with a heat inactivated bacterial mixture or with the infection of Vibrio splendidus on the cell viability and the expression of selected immune-related genes were studied. While significant low levels of damaged cells were registered in LPS-stimulated cells, the treatment with dead bacteria or V. splendidus reduced cell viability 1 h, 3 h and 6 h after treatment. The stimulation of haemocytes with LPS and dead bacteria induced changes in the expression of defender against cell death (DAD 1), thrombin, prosaposin, inhibitor of apoptosis (IAP), factor B and C3 complement component. PMID- 22051181 TI - Long-term stimulation of trout head kidney cells with the cytokines MCSF, IL-2 and IL-6: gene expression dynamics. AB - The production of salmonid leukocyte cell lines from primary cell cultures has been attempted on several occasions, however, to date only monocyte/macrophage like cell lines exist (e.g. RTS-11 and SHK-1 cells). With the increasing number of cytokines discovered in fish in recent years, many of which are growth factors for leukocytes, we now have the possibility of using these molecules to promote leukocyte development and differentiation in culture. We have generated stable cell lines transfected with a variety of plasmids expressing cytokines (Interleukin (IL)-2, IL-6 and Macrophage Colony Stimulating Factor (MCSF)), in order to produce conditioned media rich in these cytokines. The cytokine conditioned media were used to assess their activity and ability to support the growth of primary head kidney (HK) leukocyte cultures. Here, we describe a series of experiments aimed to determine which cell population(s) of primary HK cultures is supported and will grow in conditioned media containing MCSF, IL-2 or IL-6. For a period of 5 weeks, cells were incubated at 22 degrees C and media were changed every 3-4 days. Samples were taken at different time points, from freshly isolated HK cells (T0), one week post-stimulation (1-WPS), 3-WPS and 5-WPS for RNA extraction. A variety of cell lineage markers (MCSF Receptor 2 (MCSFR2) for macrophages, CD4 and CD8a for T cells and IgM heavy chain for B cells) were then analysed by real-time qPCR to study the cell population dynamics as influenced by the different recombinant cytokines in the cultures. We show here that whilst MCSF appears to drive macrophage differentiation and maintenance, IL-2 and IL-6 seem to preferentially drive lymphocyte differentiation. PMID- 22051183 TI - Informed consent and living kidney donation: more (information) is not always better. PMID- 22051182 TI - Distribution, characterization, and induction of CD8+ regulatory T cells and IL 17-producing CD8+ T cells in nasopharyngeal carcinoma. AB - BACKGROUND: CD8+ effector cells often have an antitumor function in patients with cancer. However, CD8+Foxp3+ regulatory T cells (Tcregs) and interleukin (IL)-17 producing CD8+ T cells (Tc17 cells) also derive from the CD8+ T cell lineage. Their role in the antitumor response remains largely unknown. In the present study, we aimed to investigate the distribution, characterization, and generation of CD8+ Tcregs and Tc17 cells in NPC patients. METHODS: Peripheral blood and tumor biopsy tissues from 21 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were collected, along with peripheral blood from 21 healthy donors. The biological characteristics of Tcregs and Tc17 cells from blood and tumor tissues were examined by intracellular staining, tetramer staining and fluorescence-activated cell sorting (FACS) analysis. The suppressive function of Tcregs was investigated using a proliferation assay that involved co-culture of sorted CD8+CD25+ T cells with naive CD4+ T cells in vitro. RESULTS: We observed an increased prevalence of Tcregs and Tc17 cells among tumor-infiltrating lymphocytes (TILs) and different distribution among peripheral blood mononuclear cells (PBMCs) in NPC patients. Cytokine profiles showed that the Tcregs expressed a high level of IL-10 and low level of transforming growth factor beta, whereas Tc17 cells expressed a high level of tumor necrosis factor alpha. Interestingly, both subsets expressed a high level of interferon gamma in TILs, and the Tcregs suppressed naive CD4+ T cell proliferation by a cell contact-dependent mechanism in vitro. Moreover, we demonstrated the existence of Epstein-Barr virus latent membrane protein (LMP) 1 and LMP2 antigen-specific Tcregs in NPC. CONCLUSIONS: Our data provide new insights into the composition and function of CD8+ T-cell subsets in NPC, which may have an important influence on NPC immunotherapy. PMID- 22051184 TI - A toxicological and dermatological assessment of aryl alkyl alcohols when used as fragrance ingredients. AB - The aryl alkyl alcohol (AAA) fragrance ingredients are a diverse group of chemical structures with similar metabolic and toxicity profiles. The AAA fragrances demonstrate low acute and subchronic dermal and oral toxicity. No carcinogenicity in rats or mice was observed in 2-year chronic testing of benzyl alcohol or alpha-methylbenzyl alcohol; the latter did induce species and gender specific renal adenomas in male rats at the high dose. There was no to little genotoxicity, mutagenicity, or clastogenicity in the mutagenic in vitro bacterial assays, and in vitro mammalian cell assays. All in vivo micronucleus assays were negative. NOAELs for maternal and developmental toxicity are far in excess of current human exposure levels. At concentrations likely to be encountered by consumers, AAA fragrance ingredients are non-irritating to the skin. The potential for eye irritation is minimal. With the exception of benzyl alcohol and to a lesser extent phenethyl and 2-phenoxyethyl AAA alcohols, human sensitization studies, diagnostic patch tests and human induction studies, indicate that AAA fragrance ingredients generally have no or low sensitization potential. Available data indicate that the potential for photosensitization is low. It is concluded that these materials would not present a safety concern at current levels of use as fragrance ingredients. PMID- 22051185 TI - WITHDRAWN: Estimation of flavonoids and evaluation of protective effect of Carissa opaca Stapf ex Haines fruit against CCl(4) induced nephrotoxicity in rat. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 22051186 TI - Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine. AB - Human xenobiotic-metabolizing cytochrome P450 (CYP) enzymes can each bind and monooxygenate a diverse set of substrates, including drugs, often producing a variety of metabolites. Additionally, a single ligand can interact with multiple CYP enzymes, but often the protein structural similarities and differences that mediate such overlapping selectivity are not well understood. Even though the CYP superfamily has a highly canonical global protein fold, there are large variations in the active site size, topology, and conformational flexibility. We have determined how a related set of three human CYP enzymes bind and interact with a common inhibitor, the muscarinic receptor agonist drug pilocarpine. Pilocarpine binds and inhibits the hepatic CYP2A6 and respiratory CYP2A13 enzymes much more efficiently than the hepatic CYP2E1 enzyme. To elucidate key residues involved in pilocarpine binding, crystal structures of CYP2A6 (2.4 A), CYP2A13 (3.0 A), CYP2E1 (2.35 A), and the CYP2A6 mutant enzyme, CYP2A6 I208S/I300F/G301A/S369G (2.1 A) have been determined with pilocarpine in the active site. In all four structures, pilocarpine coordinates to the heme iron, but comparisons reveal how individual residues lining the active sites of these three distinct human enzymes interact differently with the inhibitor pilocarpine. PMID- 22051187 TI - Hepatitis B virus infection among medical aste handlers in Addis Ababa, Ethiopia. AB - BACKGROUND: Healthcare wastes contain a wide range of microorganisms among which hepatitis B virus (HBV) are the most significant pathogens. No data about the prevalence of HBV among medical waste handlers is available in Addis Ababa, Ethiopia. Therefore; this study was conducted to describe the prevalence of HBV infection among medical waste handlers in Government hospitals of Addis Ababa, Ethiopia. FINDINGS: A cross sectional study was conducted among 252 medical and non-medical waste handlers working in three Government hospitals of Addis Ababa between May to July, 2010. Predesigned and tested questionnaire was used to collect soiociodemographic information. Blood sample was taken from 252 waste handlers and serum was tested for Hepatitis B surface antigen (HBsAg) and anti Hepatitis core antigen (anti-HBcAg) using Enzyme Linked Immuno Sorbent Assay.Of the 126 Medical Waste Handlers and 126 Non Medical Waste Handler, HBsAg was detected in 8 (6.3%) and 1 (0.8%), and anti-HBcAg in 60 (47.6%) and 40 (31.7%), respectively. Significant differences were observed in the detection rates of HBsAg (OR: 8, 95% CI: 1.02, 63.02; p = 0.01), Anti-HB c Ag (OR: 1.5, 95% CI: 1.1, 2.1; p = 0.01) and either markers (OR: 1.7, 95% CI: 1.2, 2.2; p = 0.001) in medical waste handlers compared to non medical waste handlers. 19.8% were trained to handle medical waste and none was immunized against HBV. CONCLUSION: This study shows a high prevalence of HBV infection in medical waste handlers compared to non medical waste handlers. Lack of training on how to handle medical waste among medical waste handlers was high. PMID- 22051188 TI - VEGF-A immunohistochemical and mRNA expression in tissues and its serum levels in potentially malignant oral lesions and oral squamous cell carcinomas. AB - The aim of the study was to investigate whether the estimation of circulating Vascular endothelial growth factor-A (VEGF-A) levels by ELISA could be used as surrogate of VEGF-A expression in tissues of pre-malignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC) as compared to that in healthy controls. The study samples comprised of tissue and blood samples from 60 PMOLs, 60 OSCC, and 20 healthy controls. Serum VEGF-A levels were determined by an ELISA based assay (Quantikine human VEGF; R & D System, Minneapolis USA). Tissue VEGF-A expression and microvessel density (MVD) were assessed by immunohistochemistry (IHC) using antibodies against VEGF-A and CD-34 on formalin fixed paraffin embedded (FFPE) tissue sections. VEGF-A mRNA expression was analyzed by real-time PCR in snap frozen tissues. Serum VEGF-A levels and immunohistochemical VEGF-A expression were significantly high in PMOLs and OSCC in comparison with controls. VEGF mRNA gene expression showed more than 50-fold increase in PMOLs and OSCC. VEGF-A levels in serum correlated in a linear fashion with the tissue expression in oral pre-malignant and malignant lesions, suggesting that the serum levels may serve as surrogate material for tissue expression of VEGF-A. PMID- 22051189 TI - Introduction: Pathology of the inner ear. PMID- 22051190 TI - Collie eye anomaly in Hokkaido dogs: case study. AB - OBJECTIVE: To describe a Hokkaido dog, one of the traditional Japanese breeds that was affected by Collie eye anomaly (CEA), and to report the genotype of this dog and the Hokkaido dog allelic frequency of the CEA-associated mutation. CASE: A nine-month-old intact female Hokkaido dog without any obvious visual disturbance was diagnosed ophthalmoscopically with CEA. Severe choroidal hypoplasia was observed in the bilateral temporal area adjacent to the optic nerve head, appearing as whitish areas. Therefore, the dog was suspected of possessing the CEA-associated mutation that was previously reported as an intronic 7.8-kilo base deletion in the canine NHEJ1 gene. PROCEDURES: SYBR Green based real-time PCR with a melting curve analysis, conventional PCR with agarose gel electrophoresis, and direct DNA sequencing were carried out to determine the genotype of the dog. Furthermore, a preliminary genotyping survey was carried out in 17 Hokkaido dogs from three kennels using the real-time PCR method, and the pedigree relationships were analyzed using their pedigree papers. RESULTS: The Hokkaido dog affected by CEA was proven to possess the CEA-associated mutation. Of these 17 Hokkaido dogs, 12 dogs were heterozygous carriers and five dogs were affected by this mutation. The preliminary genotyping survey and pedigree analysis demonstrated that the allelic frequency of the CEA-associated mutation is very high in Hokkaido dogs. CONCLUSION: These data suggest that the Hokkaido breed is highly susceptible to CEA because of the known CEA-associated mutation much like the Collie-related breeds. PMID- 22051191 TI - Hypothyroidism stimulates D2 receptor-mediated breathing in response to acute hypoxia and alters D2 receptors levels in carotid bodies and brain. AB - Hypothyroidism can depress breathing and alter dopamine D2 receptor expression and function. We hypothesized that relative to euthyroid hamsters (EH), hypothyroid hamsters (HH) contain increased D2 receptors in brain regions associated with breathing and carotid bodies (CB), and that stimulation of D2 receptors would decease ventilation more in the HH compared to the EH. Hamsters were treated with vehicle, carmoxirile (peripherally acting D2 receptor agonist), or bromocriptine (central and peripherally acting D2 receptor agonist) and breathing was evaluated during exposure to air, hypoxia, and then air. HH exhibited increased D2 receptor protein levels in the striatum and CB, but decreased levels in the paraventricular hypothalamic nucleus. Relative to vehicle, carmoxirole and bromocriptine stimulated ventilation in the HH during and following exposure to hypoxia. Only bromocriptine depressed ventilation in the EH during and after exposure to hypoxia. Thus, hypothyroidism impacts the expression of D2 receptors in the carotid body, PVN and striatum, and D2 stimulation affects ventilation remarkably differently than in EH. PMID- 22051192 TI - Avoiding the 'twilight zone': recommendations for the transition of services from adolescence to adulthood for young people with ADHD. AB - Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder that frequently persists into adulthood. However, in the UK, there is a paucity of adult services available for the increasing number of young people with ADHD who are now graduating from child services. Furthermore, there is limited research investigating the transition of young people with ADHD from child to adult services and a lack of guidance on how to achieve this effectively. This paper reviews the difficulties of young people with ADHD and their families who are transitioning between services; we review transition from the child and adult health teams' perspectives and identify barriers to the transition process. We conclude with recommendations on how to develop transition services for young people with ADHD. PMID- 22051193 TI - Filamin-A as a marker and target for DNA damage based cancer therapy. AB - Filamin-A, also called actin binding protein 280 (ABP-280), cross-links the actin filaments into dynamic orthogonal network to serve as scaffolds in multiple signaling pathways. It has been reported that filamin-A interacts with DNA damage response proteins BRCA1 and BRCA2. Defects of filamin-A impair the repair of DNA double strand breaks (DSBs), resulting in sensitization of cells to ionizing radiation. In this study, we sought to test the hypothesis that filamin-A can be used as a target for cancer chemotherapy and as a biomarker to predict cancer response to therapeutic DNA damage. We found that reduction of filamin-A sensitizes cancer cells to chemotherapy reagents bleomycin and cisplatin, delays the repair of not only DSBs but also single strand breaks (SSBs) and interstrand crosslinks (ICLs), and increases chromosome breaks after the drug treatment. By treating a panel of human melanoma cell lines with variable filamin-A expression, we observed a correlation between expression level of filamin-A protein and drug IC(50). We further inhibited the expression of filamin-A in melanoma cells, and found that this confers an increased sensitivity to bleomycin and cisplatin treatment in a mouse xenograft tumor model. These results suggest that filamin-A plays a role in repair of a variety of DNA damage, that lack of filamin-A is a prognostic marker for a better outcome after DNA damage based treatment, and filamin-A can be inhibited to sensitize filamin-A positive cancer cells to therapeutic DNA damage. Thus filamin-A can be used as a biomarker and a target for DNA damage based cancer therapy. PMID- 22051194 TI - DNA binding is essential for PprI function in response to radiation damage in Deinococcus radiodurans. AB - The extremely radioresistant bacterium Deinococcus radiodurans possesses a rapid and efficient but poorly known DNA damage response mechanism that mobilizes one third of its genome to survive lethal radiation damage. Deinococcal PprI serves as a general switch to regulate the expression of dozens of proteins from different pathways after radiation, including the DNA repair proteins RecA, PprA and SSB. However, the underlying mechanism is poorly understood. In this study, we analyzed the dynamic alteration in global transcriptional profiles in wildtype and pprI mutant strains by combining microarrays and time-course sampling. We found that PprI up-regulated transcription of at least 210 genes after radiation, including 21 DNA repair and replication-related genes. We purified PprI and a helix-turn-helix (HTH) domain mutant and found that PprI specifically bound to the promoters of recA and pprA in vitro but did not bind nonspecific double strand DNA. Chromatin immunoprecipitation (ChIP) assays confirmed that PprI specifically interacted with the promoter DNA of recA and pprA after radiation. Finally, we showed that a DNA-binding activity-deficient pprI mutant only partially restored resistance of the pprI mutant strain to gamma radiation, UV radiation, and mitomycin C. Taken together, these results indicate that DNA binding activity is essential for PprI to program the DNA repair process and cellular survival of D. radiodurans in response to radiation damage. PMID- 22051195 TI - Regulation of Actinomycin D induced upregulation of Mdm2 in H1299 cells. AB - Mdm2 is a critical negative regulator of the p53 tumor suppressor and also has many p53-independent functions. Deregulation of Mdm2 is closely associated with tumorigenesis. However, how Mdm2 is regulated in response to various stresses is not well understood. In this study, we found that Mdm2 was stabilized and upregulated upon Actinomycin D (ActD) treatment in the p53-deficient H1299 cell line. This Mdm2 upregulation was not dependent on the ribosomal protein L11, an essential player in ribosomal stress-induced p53 activation, but did require a NEDDylation-dependent mechanism. We further demonstrated that the ActD-induced Mdm2 stabilization may be modulated by the cell growth signaling, and that knockdown of Mdm2 enhanced ActD-induced cell death in H1299 cells. These results suggested a role of Mdm2 in the ribosomal stress response in the p53 deficient cells, which could be exploited in therapeutic use for treating cancers harboring p53 mutations. PMID- 22051196 TI - Low prevalence of major depressive disorder in Taiwanese adults: possible explanations and implications. AB - BACKGROUND: This study examined the prevalence of major depressive disorder (MDD), and the correlations and co-morbid conditions associated with MDD, in the adult Taiwanese population, which a previous estimate in the 1980s had found to be at the lower end of the spectrum worldwide. Possible explanations for the reported low prevalence of MDD were evaluated. METHOD: As part of a survey of common psychiatric disorders in a nationally representative sample of individuals aged >= 18 years who were non-institutionalized civilians in Taiwan, a face-to face interview using the paper version of the World Mental Health Survey of the World Health Organization (WHO) Composite International Diagnostic Interview (WMH CIDI) was conducted between 2003 and 2005. Functional impairment and help-seeking behaviors were compared between Taiwanese subjects with MDD and their counterparts in the USA. RESULTS: Among the 10 135 respondents, the lifetime prevalence of MDD was 1.20% [standard error (S.E.)=0.2%]. Individuals who were divorced or widowed, aged <= 40 years, and female were at increased risk, whereas rural residents were at lower risk for MDD. The proportion of MDD cases co-morbid with other psychiatric disorders in this study was much lower than in the US study. Only one-third of Taiwanese individuals with MDD sought help despite having twice the number of lost workdays compared with the US sample. CONCLUSIONS: Despite the low prevalence of MDD in Taiwanese adults, the pattern of low help-seeking behavior and profound functional impairment indicates much room for improvement in the early detection of and intervention in major depression in this population. PMID- 22051197 TI - Volcanic perturbations of the marine environment in South China preceding the latest Permian mass extinction and their biotic effects. AB - The Dongpan section in southern Guangxi Province records the influence of local volcanic activity on marine sedimentation at intermediate water depths (~200-500 m) in the Nanpanjiang Basin (South China) during the late Permian crisis. We analyzed ~100 samples over a 12-m-thick interval, generating palynological, paleobiological, and geochemical datasets to investigate the nature and causes of environmental changes. The section records at least two major volcanic episodes that culminated in deposition of approximately 25- to 35-cm-thick ash layers (bentonites) and that had profound effects on conditions in both the Dongpan marine environment and adjacent land areas. Intensification of eruptive activity during each volcanic cycle resulted in a shift toward conifer forests, increased wildfire intensity, and elevated subaerial weathering fluxes. The resulting increase in nutrient fluxes stimulated marine productivity in the short term but led to a negative feedback on productivity in the longer term as the OMZ of the Nanpanjiang Basin expanded, putting both phytoplankton and zooplankton communities under severe stress. Radiolarians exhibit large declines in diversity and abundance well before the global mass extinction horizon, demonstrating the diachroneity of the marine biotic crisis. The latest Permian crisis, which was probably triggered by the Siberian Traps flood basalts, intensified the destructive effects of the earlier local eruptions on terrestrial and marine ecosystems of the South China craton. PMID- 22051198 TI - The importance of pulsed lavage on interface temperature and ligament tension force in cemented unicompartmental knee arthroplasty. AB - BACKGROUND: Mechanical loosening is the most common cause of revision in unicompartmental knee arthroplasty. We determined the effect of bone lavage on tibial cement penetration and interface temperature with controlled ligament tension forces. We presumed pulsed lavage would allow increased cement penetration compared with syringe lavage. METHODS: Cemented unicompartmental knee arthroplasty was performed in 12 pairs of fresh-frozen knees. Lavage was performed using pulsed lavage on one side (A) and syringe lavage on the other (B). Cement penetration pressure, interface temperature, and ligament tension forces were continuously monitored during the operation. Screened radiographs were taken and cement penetration under the tibial plateau was measured. FINDINGS: The pulsed lavage group showed a mean cement penetration area of 187.24 (SD 36.37) mm2, whereas 144.29 (SD 35.74) mm(2) was measured in the group with syringe lavage. Cement penetration pressure was 13.29 (SD 8.69) kPa in Group A and 20.21 (SD 7.78) kPa in Group B. Maximum interface temperatures of 46.99 degrees C were observed in Group A and 45.02 degrees C in Group B. INTERPRETATION: Our data showed pulsed lavage cleansing of the cancellous tibial bone substantially improved cement penetration compared with syringe lavage without reaching the temperature threshold for bone necrosis. We recommend the routine use of pulsed lavage to improve long-term fixation. PMID- 22051199 TI - Alleviation of lung injury by glycyrrhizic acid in benzo(a)pyrene exposed rats: Probable role of soluble epoxide hydrolase and thioredoxin reductase. AB - Benzo(a)pyrene [B(a)P] is known to alter lung physiology by interfering in various intracellular pathways including alterations in NF-kappaB activities, cytokine release and cell survival. NF-kappaB suppression/activation plays a major role in cell survival status. Present investigation deals with such kind of effects of B(a)P on lungs in relation with soluble epoxide hydrolase (sEH) and thioredoxin reductase (TrxR) activities. Glycyrrhizic acid (GA), an active principle of Glycyrrhiza glabra (Licorice), is known to modulate various molecular processes. In the present study, we investigated the protective effects of GA against B(a)P induced debilities in lungs of Wistar rats. Intratracheal instillation of B(a)P significantly suppressed NF-kappaB translocation, sEH, TrxR and catalase activities in lung tissue. A marked induction of H(2)O(2) levels along with caspases activation (caspases-2, -3, -6, -8, and -9) in lung tissue after B(a)P exposure was observed. Lung injury was assessed by measuring lactate dehydrogenase (LDH), alkaline phosphatase (ALP), total cell count, total protein, neutrophil elastase activity in bronchoalveolar lavage fluid (BALF). Reduction in phospholipid content further potentiated these parameters. GA oral administration (50 and 100mg/kg b.wt.) significantly showed protection of lung epithelium by suppression of caspases activities in lung tissue and reduction of total protein, total cells, elastase activity, LDH and ALP activities along with fortification of phospholipids in BALF. Histological observations also confirm the findings in above mentioned parameters. Results indicate a strong correlation between amelioration of sEH and TrxR activities, and NF-kappaB activation. The present investigation gives an insight into probable mechanisms of lung injuries induced by short term exposures of B(a)P and prevention by glycyrrhizic acid. PMID- 22051201 TI - The lived experience of a foot burn injury from the perspective of seven Jordanians with diabetes: a hermeneutic phenomenological study. AB - Poor vision and poor pain sensation expose sufferers of diabetes to foot burn injuries. A phenomenological approach was used to illuminate the lived experience of those with diabetes who sustained foot burn injuries. Face-to-face unstructured interviews were conducted with seven patients recruited from health care facilities throughout Jordan. The interviews were digitally recorded, transcribed verbatim into Arabic, checked for accuracy and then analysed using thematic analysis. Our study highlights that household appliances are a major cause of foot burn injuries among the studied population and that culturally specific risk factors predispose Jordanians with diabetes to foot burn injuries, namely ablution for males and cooking activities for females. Participants sought health care when home remedies failed. Inconsistent management practices were identified among health care providers. Culturally specific health education programs should be made to raise patients' awareness towards avoiding possible risks at home. PMID- 22051200 TI - Multiple point action mechanism of valproic acid-teratogenicity alleviated by folic acid, vitamin C, and N-acetylcysteine in chicken embryo model. AB - The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in genetic and somatic levels, causing teratogenesis involving neurotubular defects (NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to spina bifida aperta. A diversity of nutraceutics have been tried to alleviate the risk of VPA-teratogenicity. The effect was varying. In order to promote the preventive prescription, to find out its action mechanism can be rather crucial. We used chicken embryo model to try the effect of folic acid (FA), ascorbic acid (AA), and N-acetyl cysteine (NAC). VPA at 30mM showed the higher malformation rate (66.7%) with the least mortality (22.2%). Pathological findings indicated that the cervical muscle was more susceptible to VPA injury than the ankle muscle. VPA downregulated levels of superoxide dismutase (SOD), glutathione (GSH), histone deacetylase (HDAC) and folate, and upregulated H(2)O(2) and homocysteine. FA, AA, and NAC significantly upregulated SOD, but only AA alone activated GSH. AA and NAC downregulated H(2)O(2), while FA was totally ineffective. All three nutraceutics comparably rescued HDAC with simultaneously suppressed homocysteine accumulation and folate re-elevation, although less effectively by NAC. Based on these data, we conclude VPA possesses "Multiple Point Action Mechanism". In addition to affecting the cited transcription and translation levels, we hypothesize that VPA competitively antagonize the glutamic acid to couple with pteroic acid in biosynthesis of dihydrofolic acid (DHFA). H(2)O(2) directly destroyed the NADPH reducing system at dihydrofolate reductase (DHFR) and methylene tetrahydrofolate reductase (MTHFR) levels, while completely restored by AA, an implication in preservation of intact apoenzymes. In addition, the GSH-GSSG system is sandwiched between the reducing systems NADPH/NADP and DHA AA, its net balance is highly dependent on in situ in vivo Redox state, hence folic acid transformation is varying. To rescue the VPA-induced teratogenicity, simultaneous multiple prescriptions are suggested. PMID- 22051202 TI - Trends in alcohol use among women with and without myocardial infarction in the United States: 1997-2008. AB - OBJECTIVE: This study examined the frequency and temporal trends of alcohol use among women with and without myocardial infarction (MI) in the United States. METHOD: We pooled yearly surveys from the nationally representative Behavioral Risk Factor Surveillance System between 1997 and 2008. Subjects for this study were 1,186,951 women, of whom 50,055 had a previous MI. Yearly weighted prevalence rates and frequencies of drinking behaviors were calculated for alcohol use in women with and without previous MI. RESULTS: Fewer post-MI women consumed alcohol than other women (24% vs. 46%), but the prevalence of drinking increased over time in both groups. Nearly one third of post-MI women and half of all women consumed more than one drink per day. Heavy episodic drinking (four or more drinks per day) increased over time in both groups. After multivariable adjustment, post-MI women were less likely to report any drinking or consuming more than one drink per day, but the prevalence of heavy episodic drinking and the increasing trends over time were similar in both groups. CONCLUSIONS: Heavy alcohol use and heavy episodic drinking among women in the United States increased over the past decade, regardless of MI history. Although this may have reflected the influence of national guidelines on alcohol consumption, the increase in heavy episodic drinking suggests that better efforts to educate clinicians and women about the harms from excessive alcohol are required. PMID- 22051203 TI - Heavy alcohol use and premature death from hepatocellular carcinoma in the United States, 1999-2006. AB - OBJECTIVE: The incidence rate of hepatocellular carcinoma has been rising in the United States during the last 2 decades. Heavy alcohol use has been widely recognized as one of the major etiological factors of hepatocellular carcinoma. This study sought to assess the extent to which heavy alcohol use contributed to premature death from hepatocellular carcinoma on a population scale in the United States. METHOD: We analyzed the Multiple Cause of Death public-use data sets. Using codes from the International Classification of Diseases, 10th Revision, hepatocellular carcinoma death was defined based on the underlying cause of death, and heavy alcohol use was indicated by the presence of any alcohol-induced medical conditions among the contributing causes of death. During 1999-2006 in the United States, 51,400 hepatocellular carcinoma deaths were identified from 17,727,245 natural deaths of persons age 25 or older. We conducted Poisson regression, life table, and multiple linear regression analyses to compare prevalence ratios, cumulative probabilities, and mean ages of death, respectively, from hepatocellular carcinoma by heavy alcohol use status across sex and race/ethnicity. RESULTS: Heavy alcohol use decedents had higher prevalence ratios of dying from hepatocellular carcinoma than from non-chronic liver diseases compared with those decedents without heavy alcohol use. Heavy alcohol use was associated with decreased mean ages and increased cumulative probabilities of death among hepatocellular carcinoma decedents across racial/ethnic groups in both sexes. This association was stronger among women than men and stronger among non-Hispanic Whites than non-Hispanic Blacks. CONCLUSIONS: This study provides mortality-based empirical evidence to further establish heavy alcohol consumption as one of the key risk factors contributing to premature deaths from hepatocellular carcinoma in the United States, and its effect appears more prominent among women and non-Hispanic Whites. PMID- 22051205 TI - Are changes in financial strain associated with changes in alcohol use and smoking among older adults? AB - OBJECTIVE: This study aimed to assess whether changes in levels of financial strain are associated with changes in alcohol use and smoking among older adults. METHOD: Multilevel analyses were conducted using longitudinal data from a randomly selected national sample of older adults (N = 2,352; 60% female). The data were collected in six waves during the period of 1992-2006. We estimated associations between within-person changes in levels of financial strain and the odds of engaging in heavy drinking and smoking, while also testing for the moderating effects of gender, education, and age. RESULTS: A direct association was observed between changes in levels of financial strain and the odds of heavy drinking, particularly among elderly men (odds ratio [OR] = 1.31) and those with low levels of education (OR = 1.27). A direct association between changes in levels of financial strain and the odds of smoking was also evident, particularly among the young-old (i.e., age 65 at baseline; OR = 1.44). CONCLUSIONS: Exposure to financial strain places some groups of older adults at increased risk for unhealthy drinking and smoking. If the current global financial crisis leads to increases in experiences of financial strain among older adults, alcohol and smoking problems can also be expected to increase in this population. PMID- 22051204 TI - Proposed model of the neurobiological mechanisms underlying psychosocial alcohol interventions: the example of motivational interviewing. AB - OBJECTIVE: Despite the prevalence and profound consequences of alcohol use disorders, psychosocial alcohol interventions have widely varying outcomes. The range of behavior following psychosocial alcohol treatment indicates the need to gain a better understanding of active ingredients and how they may operate. Although this is an area of great interest, at this time there is a limited understanding of how in-session behaviors may catalyze changes in the brain and subsequent alcohol use behavior. Thus, in this review, we aim to identify the neurobiological routes through which psychosocial alcohol interventions may lead to post-session behavior change as well as offer an approach to conceptualize and evaluate these translational relationships. METHOD: PubMed and PsycINFO searches identified studies that successfully integrated functional magnetic resonance imaging and psychosocial interventions. RESULTS: Based on this research, we identified potential neurobiological substrates through which behavioral alcohol interventions may initiate and sustain behavior change. In addition, we proposed a testable model linking within-session active ingredients to outside-of-session behavior change. CONCLUSIONS: Through this review, we present a testable translational model. Additionally, we illustrate how the proposed model can help facilitate empirical evaluations of psychotherapeutic factors and their underlying neural mechanisms, both in the context of motivational interviewing and in the treatment of alcohol use disorders. PMID- 22051206 TI - Anger, hostility, and aggression as predictors of persistent smoking during pregnancy. AB - OBJECTIVE: We examined the role of anger, hostility, and aggression, in addition to depression and stress, in predicting persistent smoking during pregnancy in a low-income sample. METHOD: The sample consisted of 270 pregnant women (189 smokers, 81 nonsmokers) recruited into a prospective study of prenatal cigarette exposure in the first trimester. Persistent pregnancy smoking was defined as self reporting daily smoking in at least two trimesters, a positive salivary cotinine level in at least two trimesters, or infant meconium positive for nicotine and/ or its metabolites. RESULTS: Persistent smokers reported higher prenatal stress and negative affect symptoms (depression, anger, hostility, aggression) than nonpersistent smokers or nonsmokers. However, in the context of model testing, maternal anger, hostility, and aggression each accounted for unique variance in persistent smoking, whereas symptoms of depression and stress did not. CONCLUSIONS: To date, interventions for pregnant low-income smokers have been largely ineffective. The current results suggest that anger management interventions may be particularly effective for low-income persistent pregnant smokers and may be more likely to prevent relapse than depression-focused interventions. PMID- 22051207 TI - Test of a conceptual model of partner aggression among women entering substance use disorder treatment. AB - OBJECTIVE: Despite extensive intimate partner violence (IPV) among women in substance use disorder treatment, few studies have investigated IPV risk factors within this population. Conceptual models, which have received support in other populations, propose that antisociality and generalized violence, alcohol and drug use, and relationship adjustment may be interrelated pathways that influence IPV. The purpose of this study was to test a conceptual model that integrates these individual and relationship pathways to explain IPV among women entering substance use disorder treatment. METHOD: Women entering substance use disorder treatment (N = 277) who had a male relationship partner completed measures of the following domains about themselves and their male partners: antisociality/generalized violence, heavy alcohol use, drug use, relationship adjustment, and psychological and physical IPV. RESULTS: Structural equation modeling analyses showed that the antisociality/generalized violence of each partner had direct and indirect effects on IPV. Each partner's antisociality/generalized violence was directly related to her or his physical IPV. Female antisociality/ generalized violence was indirectly related to female physical IPV via female drug use and female psychological IPV. Male antisociality/generalized violence was indirectly associated with male physical IPV via male drinking, relationship adjustment, and male psychological IPV. A reciprocal relationship was found between partners' psychological IPV but not physical IPV. When accounting for other individual and relational IPV predictors, male partners' physical IPV influenced women's physical IPV, but women's physical IPV did not influence their male partner's physical IPV. CONCLUSIONS: Both partners' antisociality/generalized violence, substance use, and overall relationship adjustment are important in understanding IPV among women entering substance use disorder treatment. PMID- 22051208 TI - Acute modafinil effects on attention and inhibitory control in methamphetamine dependent humans. AB - OBJECTIVE: Individuals who are methamphetamine dependent exhibit higher rates of cognitive dysfunction than healthy people who do not use methamphetamine, and this dysfunction may have a negative effect on the success of behavioral treatments for the disorder. Therefore, a medication that improves cognition, such as modafinil (Provigil), may serve as a useful adjunct to behavioral treatments for methamphetamine dependence. Although cognitive-enhancing effects of modafinil have been reported in several populations, little is known about the effects of modafinil in methamphetamine-dependent individuals. We thus sought to evaluate the effects of modafinil on the cognitive performance of methamphetamine dependent and healthy individuals. METHOD: Seventeen healthy subjects and 24 methamphetamine- dependent subjects participated in this randomized, double blind, placebo-controlled, crossover study. Effects of modafinil (200 mg, single oral dose) were assessed on participants' performance on tests of inhibitory control, working memory, and processing speed/attention. RESULTS: Across subjects, modafinil improved performance on a test of sustained attention, with no significant improvement on any other cognitive tests. However, within the methamphetamine-dependent group only, participants with a high baseline frequency of methamphetamine use demonstrated a greater effect of modafinil on tests of inhibitory control and processing speed than those participants with low baseline use of methamphetamine. CONCLUSIONS: Although modafinil produced limited effects across all participants, methamphetamine-dependent participants with a high baseline use of methamphetamine demonstrated significant cognitive improvement on modafinil relative to those with low baseline methamphetamine use. These results add to the findings from a clinical trial that suggested that modafinil may be particularly useful in methamphetamine-dependent subjects who use the drug frequently. PMID- 22051209 TI - Methamphetamine-using parents: the relationship between parental role strain and depressive symptoms. AB - OBJECTIVE: The methamphetamine epidemic in the United States involves a large number of men and women with dependent-age children. However, we know little about the parenting strains experienced by methamphetamine-using mothers and fathers and the relationship of these parenting strains to mental health outcomes, specifically depressive symptoms. METHOD: The primary goal of this study was to examine five dimensions of parental role strain in relation to depressive symptoms in a sample of 180 methamphetamine-using parents of dependent age children in San Diego, CA. Dimensions of parental role strain included child emotional and behavioral problems, child physical health problems, child-related financial strain, interpersonal conflict involving children, and intrapsychic strain related to children. RESULTS: Methamphetamineusing mothers reported significantly more child-related emotional and behavioral problems compared with methamphetamine-using fathers (7.9 vs. 6.8; t = 2.5, p < .05). In multiple regression analysis, higher Beck depression scores were associated with being a mother (beta = .186, p < .05), having more children younger than 18 years old (beta = .165, p < .05), less emotional support (beta = -.230, p < .01), and higher scores on intrapsychic parental role strain related to children (beta = .288, p < .01). CONCLUSIONS: These findings suggest the importance of considering the multidimensional nature of parenting strain in the development of drug treatment and counseling programs for methamphetamine-using parents. PMID- 22051210 TI - The role of academic motivation in high school students' current and lifetime alcohol consumption: adopting a self-determination theory perspective. AB - OBJECTIVE: The current study investigated the relationship between different types of academic motives-specifically, intrinsic motivation, introjected regulation, and external regulation-and high school students' current and lifetime alcohol consumption. METHOD: One thousand sixty-seven high school students completed measures of academic motivation, other school-related factors, and lifetime and current alcohol consumption. RESULTS: Using structural equation modeling, different types of motivation and school-related factors were differentially related to student drinking. Specifically, intrinsic motivation was negatively related to lifetime and current alcohol consumption. External regulation, on the other hand, was positively associated with current drinking. Grade point average was the only school-related factor related to student alcohol use. CONCLUSIONS: These findings suggest that motivation is an important construct to consider in predicting students' alcohol use, even when other more commonly studied educational variables are considered. In addition, it supports the adoption of a motivation framework that considers different types of motivation in understanding the relationship between academic motivation and alcohol use. Suggestions for incorporating the self-determination model of motivation into studies of alcohol and substance use, as well as potential impacts on intervention efforts, are discussed. In particular, it may be important to foster only certain types of motivation, rather than all types of academically-focused motives, in efforts to deter alcohol use. PMID- 22051211 TI - Progression to problem drinking among Mexican American and White European first year college students: a multiple group analysis. AB - OBJECTIVE: Problem drinking during college is a well-known phenomenon. However, predictors of progression to problematic drinking, particularly among ethnic minorities such as Mexican Americans, have received limited research attention. METHOD: The current study compared the rates and predictors of problem drinking progression from the first to the second year of college among four groups: Mexican American men, Mexican American women, White European men, and White European women (N = 215). At baseline, participants were all first-year college students who scored as nonproblem drinkers on the Young Adult Alcohol Problems Screening Test (YAAPST). Participants were classified as progressors or stable nondrinkers/nonproblem drinkers based on YAAPST scores 12 months later. Hypothesized predictors of progression included behavioral undercontrol, negative emotionality, alcohol use expectancies, and cultural orientation (Mexican American sample only). Differences were anticipated between gender and ethnic groups in both progression rates and predictors of progression. RESULTS: Twenty nine percent of the sample progressed to problematic drinking; however, no differences emerged by gender or ethnicity. For the full sample, higher behavioral undercontrol and higher negative emotionality significantly predicted progression. Differences in predictors were not found across gender and ethnic subgroups. CONCLUSIONS: The hypothesis that rates of progression to problem drinking would differ among the four gender and ethnic groups was not supported. Thus, although White European men are most often identified as at high risk for alcohol use problems, the present findings indicate that women and Mexican American students also should be targeted for prevention and/or intervention. PMID- 22051212 TI - Modeling the severity of drinking consequences in first-year college women: an item response theory analysis of the Rutgers Alcohol Problem Index. AB - OBJECTIVE: The present study examined the latent continuum of alcohol-related negative consequences among first-year college women using methods from item response theory and classical test theory. METHOD: Participants (N = 315) were college women in their freshman year who reported consuming any alcohol in the past 90 days and who completed assessments of alcohol consumption and alcohol related negative consequences using the Rutgers Alcohol Problem Index. RESULTS: Item response theory analyses showed poor model fit for five items identified in the Rutgers Alcohol Problem Index. Two-parameter item response theory logistic models were applied to the remaining 18 items to examine estimates of item difficulty (i.e., severity) and discrimination parameters. The item difficulty parameters ranged from 0.591 to 2.031, and the discrimination parameters ranged from 0.321 to 2.371. Classical test theory analyses indicated that the omission of the five misfit items did not significantly alter the psychometric properties of the construct. CONCLUSIONS: Findings suggest that those consequences that had greater severity and discrimination parameters may be used as screening items to identify female problem drinkers at risk for an alcohol use disorder. PMID- 22051213 TI - Drinking motives mediate the relationship between reinforcing efficacy and alcohol consumption and problems. AB - OBJECTIVE: Several studies have shown that demand curve indices of the reinforcing efficacy of alcohol (i.e., reports of hypothetical alcohol consumption and expenditures across a range of drink prices) are associated with alcohol-related outcomes. A next logical step in this area of research is to examine potential mediators of this direct relationship. It is possible that enhancement and coping drinking motives serve as an intermediary of the reinforcing efficacy-alcohol use relationship, such that higher reinforcing efficacy is associated with increased motivation to drink, which is then associated with greater alcohol use and problems. METHOD: Data were collected from 215 college undergraduates who reported drinking in the past 30 days. RESULTS: The demand curve reinforcing efficacy indices O(max) (maximum alcohol expenditure) and intensity (consumption level when drinks were free) demonstrated the strongest and most consistent associations with alcohol use, problems, and motives. Results from two structural equation models indicated that enhancement and coping motives mediated the relationship between reinforcing efficacy and alcohol use and alcohol-related problems. CONCLUSIONS: These results suggest that the motivational effects of the behavioral economic variable reinforcing efficacy on problematic alcohol use are in part mediated by increases in enhancement and coping motives for drinking. PMID- 22051214 TI - Influence of religiosity on 12-step participation and treatment response among substance-dependent adolescents. AB - OBJECTIVE: Religious practices among adults are associated with more 12-step participation which, in turn, is linked to better treatment outcomes. Despite recommendations for adolescents to participate in mutual-help groups, little is known about how religious practices influence youth 12-step engagement and outcomes. This study examined the relationships among lifetime religiosity, during-treatment 12-step participation, and outcomes among adolescents, and tested whether any observed beneficial relation between higher religiosity and outcome could be explained by increased 12-step participation. METHOD: Adolescents (n = 195; 52% female, ages 14-18) court-referred to a 2-month residential treatment were assessed at intake and discharge. Lifetime religiosity was assessed with the Religious Background and Behaviors Questionnaire; 12-step assessments measured meeting attendance, step work (General Alcoholics Anonymous Tools of Recovery), and Alcoholics Anonymous (AA)/Narcotics Anonymous (NA) related helping. Substance-related outcomes and psychosocial outcomes were assessed with toxicology screens, the Adolescent-Obsessive Compulsive Drinking Scale, the Children's Global Assessment Scale, and the Narcissistic Personality Inventory. RESULTS: Greater lifetime formal religious practices at intake were associated with increased step work and AA/NA-related helping during treatment, which in turn were linked to improved substance outcomes, global functioning, and reduced narcissistic entitlement. Increased step work mediated the effect of religious practices on increased abstinence, whereas AA/NA-related helping mediated the effect of religiosity on reduced craving and entitlement. CONCLUSIONS: Findings extend the evidence for the protective effects of lifetime religious behaviors to an improved treatment response among adolescents and provide preliminary support for the 12-step proposition that helping others in recovery may lead to better outcomes. Youth with low or no lifetime religious practices may assimilate less well into 12-step-oriented treatment and may need additional 12-step facilitation, or a different approach, to enhance treatment response. PMID- 22051215 TI - Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. AB - OBJECTIVE: The efficacy of naltrexone (Revia, Vivitrol) for the treatment of alcohol dependence exhibits a high degree of heterogeneity. The aim of the current study was to evaluate the extent to which variability in patient adherence to treatment contributed to the range of clinical responses observed during naltrexone treatment. METHOD: A systematic review was conducted of efficacy trials of naltrexone for the treatment of alcohol dependence to evaluate the level of adherence monitoring. RESULTS: Of 49 identified trials, 22 (49%) met the inclusion criteria of being randomized, double-blind, placebo-controlled trials that reported adherence. The "adherence-assurance score" of these trials was calculated as a function of the frequency with which "low," "moderate," or "high" confidence levels of adherence monitoring were used. Of these 22 randomized, controlled trials, only 3 (14%) met criteria for high levels of adherence assurance, 5 (23%) met medium adherenceassurance criteria, and 14 (64%) met low adherence criteria. Of the three high-assurance studies, one used direct supervision of thrice-weekly oral dosing of naltrexone, and two used extended release injectable formulations of naltrexone administered once per month. The Spearman correlation between risk ratios for return to heavy drinking (for naltrexone vs. placebo) and the level of adherence assurance (low vs. medium vs. high) was significant (r = -.62, p = .025). CONCLUSIONS: These findings suggest that the modest effect sizes for naltrexone reported in systematic reviews and meta-analyses may be attributable, at least in part, to variability in naltrexone adherence rates. High-assurance adherence strategies should be standard practice in clinical trials of medications being evaluated for the treatment of alcohol dependence. PMID- 22051216 TI - Vulnerability to the rapid ("telescoped") development of alcohol dependence in individuals with anxiety disorder. AB - OBJECTIVE: The frequent co-occurrence of alcohol dependence and anxiety disorder is a long-standing clinical conundrum. An underdeveloped perspective on this issue concerns the impact of a co-occurring anxiety disorder on the sequence and developmental course of alcohol-related milestones. Extrapolating from the body of basic science indicating overlap in the neurobiological processes associated with both anxiety disorder and alcohol dependence-particularly those involving the hypothalamic-pituitary-adrenal axis and elements of the amygdala- we hypothesized that anxiety-disordered individuals are vulnerable to the rapid development of alcohol dependence. Specifically, we predicted that the time from pre-dependence alcohol milestones (e.g., age at which regular drinking began) to post-dependence alcohol milestones would be briefer ("telescoped") among those with an anxiety disorder. METHOD: Seventy-eight individuals with alcohol dependence who had recently begun a chemical dependency treatment program underwent a diagnostic interview to determine the presence of current anxiety disorders and to establish the age at which several alcohol use and dependence milestones were first achieved. RESULTS: We found that, compared with others in the sample, anxiety-disordered individuals transitioned significantly more quickly from the time they first began drinking regularly and first began getting drunk regularly to the onset of alcohol dependence, as well as from most pre dependence alcohol milestones to the point at which their alcohol dependence was most severe. CONCLUSIONS: Individuals with anxiety disorders transition from regular drinking to alcohol dependence more rapidly than do individuals without anxiety disorders. These findings contribute to an improved understanding of the etiology of comorbidity and suggest novel directions for future research. PMID- 22051217 TI - Behavioral approach system moderates the prospective association between the behavioral inhibition system and alcohol outcomes in college students. AB - OBJECTIVE: Reinforcement sensitivity theory (RST) is a useful framework for understanding alcohol use, including problematic drinking among college students. Although the link between the behavioral approach system (BAS) and drinking is well established, the role of the behavioral inhibition system (BIS) is less well studied, and findings have been mixed. Consistent with RST, the relationship between BIS and problematic drinking may be moderated by BAS, but tests of the BIS * BAS interaction have been scarce. We hypothesized that high BIS would be a risk factor for subsequent problematic drinking in combination with an elevated BAS, whereas BIS would protect against subsequent problematic drinking in the context of low levels of BAS. METHOD: College student drinkers (N = 638; 66% women) at two universities completed online measures of BIS, BAS, alcohol use, and alcohol problems at matriculation (Time 1 [T1]) and again 1 year later (Time 2 [T2]). RESULTS: Regression analyses of alcohol use and problems were performed with BIS, BAS, and the BIS * BAS interaction as predictors. The interaction was not statistically significant in cross-sectional models (T1 alcohol outcomes), but it was a significant prospective predictor of T2 alcohol use (marginal) and T2 alcohol problems. Simple slopes analyses revealed that BIS was a positive predictor of T2 alcohol use and problems at high but not low levels of BAS, albeit this effect was less reliable for use. CONCLUSIONS: Our findings enhance interpretation of RST, demonstrating a complex link between BIS and problematic drinking risk, one that is moderated by BAS. The prospective nature of these associations suggests that, together, BIS and BAS may promote increases in problematic drinking over time, highlighting the need for targeted interventions during the first year of college. PMID- 22051218 TI - Brief report of a test of differential alcohol risk using sibling attributions of paternal alcoholism. AB - OBJECTIVE: Parental alcoholism is generally found to be a strong predictor of alcohol misuse. Although the majority of siblings agree on the presence of parental alcohol issues, there is a significant minority who do not. METHOD: The current study analyzed sibling data from the 1979 National Longitudinal Survey of Youth using multilevel modeling, which accounts for the nested structure of the data. These analyses permitted a test of whether (a) identifying one's father as an alcoholic predicted greater risk of alcohol problems, (b) being from a family whose siblings did not all agree on the presence of paternal alcoholism increased the likelihood of alcohol problems, and (c) risk of alcohol misuse significantly differed among individuals from families in which there was familial disagreement about paternal alcoholism. RESULTS: Results show that individuals who identified their father as an alcoholic were themselves more likely to have alcohol issues as compared with individuals both within and between families who did not identify their father as an alcoholic. Risk was similar for individuals in families in which there was disagreement about paternal alcoholism compared with individuals from families in which everyone agreed on the presence of paternal alcoholism. Moreover, there was not a significant interaction between paternal alcoholism attributions and familial disagreement. CONCLUSIONS: Findings indicate that in the case of child reports of paternal alcoholism, the increased risk of alcohol problems holds true regardless of the accuracy of an individual's assessment. These results may be not only because of the impact of paternal alcoholism on a person's alcohol misuse but also because of a person's alcohol problems potentially influencing his or her perceptions of familial alcohol related behaviors. PMID- 22051219 TI - Social network characteristics and heavy episodic drinking among women at risk for HIV/sexually transmitted infections. AB - OBJECTIVE: Social networks can either negatively or positively influence a variety of behaviors, including alcohol use. This study examined social network characteristics that are risk factors for and protective factors against heavy episodic drinking among a sample of women at risk for HIV/sexually transmitted infections. METHOD: This was a cross-sectional study using baseline data from 567 impoverished women participating in an HIV prevention study in Baltimore, MD. Data were collected through face-to-face interviews at a community-based research clinic. Heavy episodic drinking was defined as six or more drinks per drinking episode on at least a weekly basis. We examined network characteristics, including structure and function and their association with heavy episodic drinking. Multivariate logistic regression was used, adjusting for individual level factors, such as drug use, demographics, and depression. RESULTS: Approximately 21% of the sample engaged in heavy episodic drinking at least weekly. Controlling for individual-level factors, women who engaged in heavy episodic drinking had fewer social network members (a) who were in drug treatment, adjusted odds ratio (AOR) = 0.65, 95% CI [0.49, 0.88]; (b) who were employed, AOR = 0.89, 95% CI [0.79, 0.99]; and (c) with whom the participant socialized, AOR = 0.74, 95% CI [0.63, 0.96]. Women who engaged in heavy episodic drinking had a significantly higher number of social network members with whom they drank alcohol, AOR = 1.71, 95% CI [1.43, 2.03]. CONCLUSIONS: Social network characteristics are both protective and risk factors for heavy episodic drinking among women. Interpersonal interventions, such as peer education, may be a useful strategy to decrease heavy episodic drinking and its subsequent outcomes among women. PMID- 22051220 TI - Determining specific competencies for General Internal Medicine residents (PGY 4 and PGY 5). What are they and are programs currently teaching them? A survey of practicing Canadian General Internists. AB - BACKGROUND: General Internal Medicine (GIM) has recently been approved as a subspecialty by the Royal College of Physicians and Surgeons of Canada. As such, there is a need to define areas of knowledge that a General Internist must learn in those two years of training. There is limited literature as to what competencies are needed in a GIM practice. Draft competencies for GIM (4th and 5th year residents in internal medicine) training were developed over eight years with input from many stakeholders. Practicing General Internists were surveyed and asked their perspective as to the level of importance of each of these competencies for GIM training. They were also asked if training gaps exist in current training programs. The survey was offered widely online in both English and French to gain perspectives from as many different contexts as possible. RESULTS: 157 General Internists, in practice on average for 15 years, responded from all of Canada's provinces and territories. Practice profiles were diverse (large urban centers to rural centers). The majority of the competencies surveyed were perceived as important to attain at least proficiency in. Perioperative care, risk reduction, and the management of common, emergent, and complex internal medicine problems were identified as key areas to focus training programs on, with respondents perceiving these should be mastered to an expert level. Training gaps were identified, most frequently in that of the manager role (example managing practice). CONCLUSIONS: This is the first study we are aware of to attempt to isolate the opinions of practicing Canadian General Internists as to the major competencies that should be mastered as a General Internist. We suggest that "generalism" in the context of GIM, does not mean a bit of knowledge about everything but that defined objectives for training in this 'newest' of Royal College subspecialties can be identified. This includes mastery of core areas such as perioperative care, risk reduction, and management of common, emergent and multiple internal medicine problems. The training gaps identified need to be addressed to ensure that General Internists continue to provide excellence in health care delivery. PMID- 22051221 TI - Characterization of the normal dark adaptation curve of the horse. AB - OBJECTIVE: The goal of this work is to study the dark adaptation curve of the normal horse electroretinogram (ERG). PROCEDURES: The electroretinographic responses were recorded from six healthy female ponies using a contact lens electrode and a mini-Ganzfeld electroretinographic unit. The horses were sedated intravenously with detomidine, an auriculopalpebral nerve block was then performed, and the pupil was fully dilated. The ERG was recorded in response to a low intensity light stimulus (30 mcd.s/m(2) ) that was given at times (T) T = 5, 10, 15, 20, 25, 30, 40, 50, and 60 min of dark adaptation. Off-line analysis of the ERG was then performed. RESULTS: Mean b-wave amplitude of the full-field ERG increased continuously from 5 to 25 min of dark adaptation. The b-wave amplitude peaked at T = 25, however, there was no statistical significance between T = 20 and T = 25. The b-wave amplitude then remained elevated with no significant changes until the end of the study at T = 60 (P > 0.49). The b-wave implicit time increased continuously between T = 5 and T = 20, then gradually decreased until T = 60. No distinct a-wave was observed during the testing time. CONCLUSIONS: Evaluation of horse rod function or combined rod/cone function by means of full-field ERG should be performed after a minimum 20 min of dark adaptation. PMID- 22051222 TI - The incidence of experimental smoking in school children: an 8-year follow-up of the child and adolescent behaviors in long-term evolution (CABLE) study. AB - BACKGROUND: Studies have established that most regular adult smokers become addicted in their adolescent years. We investigated the incidence of and risk factors associated with initial experimental smoking among a group of school children who were followed for 8 years. METHODS: We used cohort data collected as part of the Child and Adolescent Behaviors in Long-term Evolution (CABLE) study, which selected nine elementary schools each from an urban area (Taipei City) and a rural area (Hsingchu county) in northern Taiwan. From 2002 to 2008, children were asked annually whether they had smoked in the previous year. An accelerated lifetime model with Weibull distribution was used to examine the factors associated with experimental smoking. RESULTS: In 2001, 2686 4th-graders participated in the study. For each year from 2002 to 2008, their incidences of trial smoking were 3.1%, 4.0%, 2.8%, 6.0%, 5.3%, 5.0% and 6.0%, respectively. There was an increase from 7th to 8th grade (6.0%). Children who were males, lived in rural areas, came from single-parent families, had parents who smoked, and had peers who smoked were more likely to try smoking earlier. The influence of parents and peers on experimental smoking demonstrated gradient effects. CONCLUSIONS: This study used a cohort to examine incidence and multiple influences, including individual factors, familial factors, and community factors, on experimental smoking in adolescents. The findings fit the social ecological model, highlighting the influences of family and friends. School and community attachment were associated with experimental smoking in teenagers. PMID- 22051224 TI - The future of fMRI and genetics research. AB - I provide a brief and subjective view of where the field of imaging genetics is heading. After recapitulating early debates between imagers and geneticists revolving around the topic of candidate gene studies, I point out the importance of genome-wide significant, rare and common variants. I propose that the next stages will be dominated by large-scale multi-site studies that will enable the examination of rare-high penetrance variants and methodological developments that will be required to properly assess the effects of pleiotropy, epistasis, and gene-by environment interactions. The incorporation of new sources of biological information such as whole genome sequencing, proteomic, lipidomic and expression profiles and cellular models derived from induced pluripotent stem cells opens new vistas for imaging genetics in a translational enterprise that is ultimately hoped to improve and create therapeutic options for psychiatric disorders. PMID- 22051223 TI - Cross-correlation: an fMRI signal-processing strategy. AB - The discovery of functional MRI (fMRI), with the first papers appearing in 1992, gave rise to new categories of data that drove the development of new signal processing strategies. Workers in the field were confronted with image time courses, which could be reshuffled to form pixel time courses. The waveform in an active pixel time-course was determined not only by the task sequence but also by the hemodynamic response function. Reference waveforms could be cross-correlated with pixel time courses to form an array of cross-correlation coefficients. From this array of numbers, colorized images could be created and overlaid on anatomical images. An early paper from the authors' laboratory is extensively reviewed here (Bandettini et al., 1993. Magn. Reson. Med. 30:161-173). That work was carried out using the vocabulary of vector algebra. Cross-correlation methodology was central to the discovery of functional connectivity MRI (fcMRI) by Biswal et al. (1995. Magn. Reson. Med. 34:537-541). In this method, a whole volume time course of images is collected while the brain is nominally at rest and connectivity is studied by cross-correlation of pixel time courses. PMID- 22051225 TI - Characterization of cytokines associated with Th17 cells in the eyes of horses with recurrent uveitis. AB - OBJECTIVE: Equine recurrent uveitis (ERU) is a spontaneous disease that is the most common cause of blindness in horses, affecting up to 15% of the horse population. Th17 cells are a major cell population driving the pathogenesis in several mouse models of autoimmune inflammation, including experimental autoimmune uveitis. The purpose of this study is to investigate the role a Th17 cell-mediated response plays in the pathogenesis of ERU. PROCEDURE: Banked, Davidson's-fixed equine globes histopathologically diagnosed with ERU (n = 7) were compared immunohistochemically with healthy control globes (n = 7). Immunohistochemical staining was performed using a pan-Leptospira antibody and antibodies against IL-6, IL-17, and IL-23. Additionally, immunostaining was performed for T-cell (CD3) and B-cell (CD79alpha) markers. Specificity of immunoreactivity was confirmed by western blot analysis. RESULTS: Immunohistochemical staining was positive for IL-6, IL-17, and IL-23 within the cytoplasm of nonpigmented ciliary epithelial cells and mononuclear inflammatory cells infiltrating the iris, and ciliary body of ERU horses (n = 7) but negative in controls (n = 7). ERU-affected eyes were CD3 positive (n = 7) and CD79alpha negative (n = 7). Staining for Leptospira was negative in all ERU and control globes. CONCLUSIONS: Strong immunoreactivity for IL-6, IL-17, and IL-23, in conjunction with the fact that T lymphocytes are the predominating inflammatory cells present in ERU, suggests that IL-17-secreting helper T-cells play a role in the pathogenesis of ERU. These findings suggest that horses with ERU may serve as a naturally occurring animal model for autoimmune uveitis. PMID- 22051226 TI - The challenge of informed consent for increased risk living donation and transplantation. AB - The Organ Procurement and Transplantation Network (OPTN) mandates that organ recipients provide "specific informed consent" before accepting organs that the OPTN defines as "increased risk". However, the OPTN does not provide specific guidelines for what information should be disclosed to potential recipients. Such vagueness opens the door to inadequate informed consent. This paper examines the ethical dimensions of informed consent when the prospective living donor has self reported behaviors associated with increased risk for infection transmission. Donor privacy is a primary ethical concern that conflicts with recipients' informed consent for use of increased risk organs. We propose that both the increased risk status and the specific behavior be disclosed to the recipient. Because the actual risk posed is linked to the type of risk behavior, disclosure is therefore needed to make an informed decision. The donor's risk behavior is material to recipients' decision making because it may impact the donor-recipient relationship. This relationship is the foundation of the donation and acceptance transaction, and thus comprises a critical feature of the recipient's informed consent. Optimizing a recipient's informed consent is essential to protecting patient safety and autonomy. PMID- 22051227 TI - Influence of index finger proximal interphalangeal joint arthrodesis on precision pinch kinematics. AB - PURPOSE: To evaluate the impact of proximal interphalangeal (PIP) joint arthrodesis on the kinematics of precision pinch. METHODS: Eleven healthy subjects performed index finger-thumb pinch motions under 4 conditions: unrestricted thumb and index finger (CONTROL) and fusion of the PIP joint of the index finger in flexion of 30 degrees (PIP30), 40 degrees (PIP40), and 50 degrees (PIP50). Fusion was simulated with metallic splints. Kinematics of the thumb and index finger were recorded with a motion capture system. RESULTS: Proximal interphalangeal joint fusion at 30 degrees , 40 degrees , and 50 degrees restricted maximal pinch span between the thumb tip and index finger tip by 6%, 10%, and 14%, respectively. At the time of pulp contact, PIP fusion led to an increase in index metacarpophalangeal joint flexion angle for the PIP30 condition and an increase in variability of thumb tip location for the PIP50 condition. Furthermore, the dynamic coordination between joint angles throughout the movement was affected by PIP fusion. CONCLUSIONS: This study reports impairment in the kinematics of precision pinch associated with index finger PIP joint fusion. A PIP joint fusion at 40 degrees to 50 degrees leads to a more natural precision pinch posture, but it restricts the aperture and reduces pinch precision. PMID- 22051228 TI - Lunate fractures in the face of a perilunate injury: an uncommon and easily missed injury pattern. AB - Lunate fractures are rare and are usually associated with high-energy trauma. Typically, they are described in isolation or with associated carpal injuries such as scaphoid, capitate, or radial styloid fractures. We report a case of a complex lunate fracture in combination with a perilunate dissociation injury. PMID- 22051229 TI - Open reduction internal fixation versus percutaneous pinning with external fixation of distal radius fractures: a prospective, randomized clinical trial. AB - PURPOSE: The purpose of this randomized clinical trial was to investigate the functional outcomes of the surgical treatment of distal radius fractures, comparing treatment by external fixation and percutaneous pinning to open reduction and internal fixation (ORIF) using a plate. METHODS: We randomized 53 patients with distal radius fractures that failed closed reduction and casting to ORIF (n = 27) or external fixation (n = 26). For pragmatic reasons, the choice of ORIF was left to the surgeon's discretion (early recruitment, dorsal plates [n = 9]; later recruitment, volar locked plates [n = 18]). Outcomes were measured before surgery, at 6 weeks, and at 3, 6, and 12 months and included the Patient Rated Wrist Evaluation (PRWE); Disabilities of the Arm, Shoulder, and Hand; range of motion; grip strength; and serial radiographic analysis. Generalized linear modeling using repeated measures was used to identify differences in outcome scores between fixation types over time. Other continuous variables were analyzed using the Student t-test or one-way analysis of variance for multiple groups. RESULTS: There were no differences in the demographic characteristics or fracture severity between groups. Based on generalized linear modeling, on average, the ORIF group scored 11 points lower on the PRWE across all time points compared to the external fixation group. The PRWE detected higher pain and disability with external fixation before surgery, at 6 weeks, and at 3 months. Using generalized linear modeling, a post hoc subgroup analysis identified significantly better (15 point advantage) PRWE scores averaged across all time points with volar locking plates compared to both external fixation and dorsal plating. CONCLUSIONS: The PRWE scores were significantly lower for patients treated with ORIF compared to those with external fixation, with the best outcomes observed with volar locking plates. These advantages were observed in the early postoperative period, and overall scores equalized at 1 year. A higher mean initial preoperative PRWE score was seen with external fixation, perhaps indicating a more severe initial injury. Given this difference, the interpretation of these results is not clear. PMID- 22051230 TI - Osseous and ligamentous scaphoid anatomy: Part I. A systematic literature review highlighting controversies. AB - PURPOSE: The interpretation of scaphoid anatomy and kinematics is confusing and controversial. This results from a lack of consensus on the anatomy of the ligaments attaching to the scaphoid and an overwhelming variety of substantially different anatomic descriptions and classification systems of the wrist joint in the literature. The present study systemically reviews the consistencies or inconsistencies of the various scaphoid ligament descriptions and aims to clarify and unify different concepts and classification systems. METHODS: We performed a systematic search of the medical literature from 1950 to 2010. We included all descriptive reports of the anatomy or morphology of the scaphoid, ligaments, or both. With the aim to describe the best available evidence, we considered all anatomical descriptions but emphasized a selection of the most frequently cited articles. RESULTS: The literature search resulted in 555 potentially eligible descriptive reports, 58 of which met the inclusion criteria and were included in the review. Variations in the anatomic descriptions appear to be mostly due to the difficulty of identifying individual interdigitating ligaments or bundles by macroscopic dissections, as well as the interindividual variability in ligament anatomy. The most important areas of controversy in the scaphoid ligament attachments include the radial collateral ligament, dorsal radiocarpal ligament, dorsal intercarpal ligament, volar scaphotriquetral ligament, and scaphotrapezium trapezoid ligament. CONCLUSIONS: None of the scaphoid ligaments other than the scaphocapitate ligament have been described consistently. Future research is required to verify the ligament attachments that currently have the most controversial descriptions, while addressing the interindividual variability of ligament insertions and morphology. CLINICAL RELEVANCE: Thorough knowledge of the anatomy will enhance our understanding of the kinematics of the scaphoid. PMID- 22051231 TI - Morphology of the cubital tunnel: an anatomical and biomechanical study with implications for treatment of ulnar nerve compression. AB - PURPOSE: The purpose of this study is to provide a thorough understanding of the anatomy of the cubital tunnel and to outline specific anatomical parameters of the cubital tunnel retinaculum (CuTR) that might aid in the management of ulnar nerve problems. The hypotheses of this study are (1) that the nerve elongates with elbow flexion and (2) that the cross-sectional area of the cubital tunnel is inversely proportional to the degree of elbow flexion. METHODS: Eleven fresh frozen cadaver arms were dissected at the medial elbow. The CuTR was identified, and its thickness was measured. After excising the CuTR, we measured the elongation of the anterior and posterior aspects of the ulnar nerve, as well as the length of the CuTR origin/insertion, at increasing intervals of elbow flexion (15 degrees , 30 degrees , 45 degrees , 90 degrees , 120 degrees , and 135 degrees ). Using 3-dimensional digitization technology, the surface of the cubital tunnel was recorded at 4 positions of elbow flexion (15 degrees , 45 degrees , 90 degrees , and 135 degrees ) and analyzed to define the tunnel geometry. RESULTS: The CuTR origin-to-insertion length and the ulnar nerve length both increased significantly with increasing flexion angle. Both lengths at 90 degrees , 120 degrees , and 135 degrees of elbow flexion were greater than at 15 degrees or 30 degrees . The cubital tunnel area was significantly less at 135 degrees compared to either 45 degrees or 90 degrees of flexion. There was a linear relationship between the cubital tunnel area of the different arms with the corresponding nerve cross-sectional area when measured at the level of the epicondyle and when the arm was at 90 degrees of elbow flexion. CONCLUSIONS: The CuTR begins to stretch at 60 degrees of flexion and continues to stretch with increasing flexion. Similarly, the ulnar nerve is more taut in flexion. The area within the cubital tunnel decreases beyond 90 degrees of elbow flexion. CLINICAL RELEVANCE: Understanding the dynamic anatomical relationships of the cubital tunnel might help in the safe treatment of cubital tunnel syndrome when using minimally invasive techniques and instrumentation. PMID- 22051232 TI - Comparison of third toe joint cartilage thickness to that of the finger proximal interphalangeal (PIP) joint to determine suitability for transplantation in PIP joint reconstruction. AB - PURPOSE: To compare the cartilage thickness of the third toe joints to the finger proximal interphalangeal (PIP) joints to assess the appropriateness of using third toe osteochondral grafts for finger PIP joint reconstruction. METHODS: A laser scanner was used to construct 3-dimensional computer models of 6 matched cadaver right third toe PIP joints, condyles of the third toe middle phalanx, and finger PIP joints with and without cartilage. Cartilage distribution patterns were computed and analyzed for each surface. The cartilage thickness of both sides of the third toe PIP joint and the third toe middle phalanx condyles were compared to the PIP joint of the fingers. A total of 18 third toe and 48 finger joint surfaces were analyzed. RESULTS: For the third toe middle phalanx condyles, the mean thickness was 0.20 +/- 0.09 mm with a maximum of 0.52 +/- 0.18 mm, and a coefficient of variation (CV%; a measure of uniformity of cartilage distribution) of 62. For the third toe proximal phalanx condyles, the mean cartilage thickness was 0.26 +/- 0.10 mm with a maximum thickness of 0.56 +/- 0.14 mm and a CV% of 44. The mean thickness, maximum thickness, and CV% of the finger proximal phalanx condyles was 0.43 +/- 0.11 mm, 0.79 +/- 0.16 mm, and 31, respectively. For the third toe middle phalanx base, the mean thickness was 0.28 +/- 0.06 mm with a maximum of 0.47 +/- 0.09 mm and a CV% of 34, compared to the finger middle phalanx base mean of 0.40 +/- 0.12 mm with a maximum of 0.67 +/- 0.14 mm and a CV% of 27. CONCLUSIONS: There were significant differences in cartilage thickness between the third toe and the fingers in this study. However, fewer differences were observed with the third toe middle phalanx base cartilage thickness than with the third toe condyles in comparison to the fingers. PMID- 22051233 TI - Abduction in internal rotation: a test for the diagnosis of axillary nerve palsy. AB - PURPOSE: To describe and validate the use of a test of abduction in internal rotation for the assessment of axillary nerve injury. METHODS: A total of 14 male patients with a mean age of 29 years (SD +/- 6 y), with axillary nerve lesions lasting an average of 6 months, participated. We measured their shoulder range of motion. In the upright position, with the trunk bending forward, we asked our patients to actively extend the shoulder (swallowtail test), and then we extended the shoulders and asked each patient to hold them in that position (deltoid extension lag test). For the abduction in internal rotation test, we asked patients to abduct the shoulder in internal rotation. If full abduction compared with the normal contralateral side was not possible, the examiner passively held the affected limb in maximal abduction and internal rotation. The patient was instructed to maintain the position when the examiner released the limb. In each test, any lag compared with the normal side accounted for deltoid palsy. RESULTS: All patients exhibited abduction beyond horizontal and full external rotation. The swallowtail test and the deltoid extension lag test identified the axillary nerve lesion in 10 of 14 patients. The abduction in internal rotation test recognized the axillary nerve injury in all 14. The average difference in the range of abduction in internal rotation between the normal and affected side was 37 degrees (abduction lag). CONCLUSIONS: Compensatory abduction in axillary nerve palsy has been attributed to the action of the supraspinatus, biceps, coracobrachialis, and pectoralis major. During abduction in internal rotation, compensatory abduction is impaired, clearly indicating deltoid muscle dysfunction. PMID- 22051234 TI - An all-inside technique for arthroscopic suturing of the volar scapholunate ligament. AB - Repair of the volar scapholunate ligament has not been performed arthroscopically. We present an all-inside technique that presents closure of the anterior scapholunate interval. A Tuohy needle and a resorbable suture are all that is required. PMID- 22051235 TI - Unilateral congenital terminal finger absences: a condition that differs from symbrachydactyly. AB - PURPOSE: To describe a type of nonhereditary unilateral transverse deficiency, which we have named hypodactyly, that is distinct from symbrachydactyly or amniotic disruption sequence. METHODS: We identified 19 patients with unilateral congenital anomalies consisting of absent or short bulbous fingers that lack terminal ectodermal elements. Medical records and radiographs were retrospectively reviewed and contrasted with the typical findings of symbrachydactyly and amniotic disruption sequence. RESULTS: No associated syndromes or potentially causative diagnoses were identified in the hypodactyly patients. The digital absences were of a truncated pattern with thickened, tubular soft tissue coverage. Radiographs revealed a pattern of severity progression that is different from that of symbrachydactyly. Distal phalanges were the bony elements absent most frequently, followed sequentially by the middle phalanx and proximal phalanx. In all cases, metacarpals were present. Unlike symbrachydactyly, the ulnar 2 digits were more involved than the index and long fingers, and the thumb was the least involved digit. CONCLUSIONS: Hypodactyly appears to be a congenital hand anomaly that is clinically and radiographically different from symbrachydactyly or amniotic disruption sequence and is presumed to be caused by a distinct pathomechanism. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV. PMID- 22051236 TI - Transferrin-conjugated curcumin-loaded superparamagnetic iron oxide nanoparticles induce augmented cellular uptake and apoptosis in K562 cells. AB - Superparamagnetic iron oxide nanoparticles are currently used for precise drug delivery and as an image contrast agent. In the present study, the potentiality of curcumin-loaded magnetic nanoparticles (Cur-MNPs) for the treatment of chronic myeloid leukemia (CML) was investigated. For active therapy, transferrin (Tf) ligand was further conjugated to Cur-MNPs, which demonstrated enhanced uptake compared to Cur-MNPs in p210bcr/abl-positive cell line (K562). Cur-MNPs demonstrated greater and sustained anti-proliferative activity in a dose- and time-dependent manner; however, with the advent of a magnetic field the anti proliferative activity of Cur-MNPs as well as Tf-Cur-MNPs was enhanced due to higher cellular uptake with enhanced cytotoxicity activity. Down-regulation of Bcr-Abl protein activates intrinsic apoptotic pathways for promoting anti leukemic responses. Our in vitro results advocate potential clinical applications of Cur-MNPs by activating multiple signaling pathways for provoking the anti leukemic activity. PMID- 22051237 TI - Synthesis of biomimetic segmented polyurethanes as antifouling biomaterials. AB - Controlling the non-specific adsorption of proteins, cells and bacteria onto biomaterial surfaces is of crucial importance for the development of medical devices with specific levels of performance. Among the strategies pursued to control the interactions between material surfaces and biological tissues, the immobilization of non-fouling polymers on biomaterial surfaces as well as the synthesis of the so-called biomimetic polymers are considered promising approaches to elicit specific cellular responses. In this study, in order to obtain materials able to prevent infectious and thrombotic complications related to the use of blood-contacting medical devices, heparin-mimetic segmented polyurethanes were synthesized and fully characterized. Specifically, sulfate or sulfamate groups, known to be responsible for the biological activity of heparin, were introduced into the side chain of a carboxylated polyurethane. Due to the introduction of these groups, the obtained polymers possessed a higher hard/soft phase segregation (lower glass transition temperatures) and a greater hydrophilicity than the pristine polymer. In addition, the synthesized polymers were able to significantly delay the activated partial thromboplastin time, this increased hemocompatibility being related both to polymer hydrophilicity and to the presence of the -SO3H groups. This last feature was also responsible for the ability of these biomimetic polymers to prevent the adhesion of a strain of Staphylococcus epidermidis. PMID- 22051238 TI - Strontium promotes cell proliferation and suppresses IL-6 expression in human PDL cells. AB - This study was designed to investigate the effect of strontium on human PDL cells in vitro. Strontium is used to treat osteoporosis because of its bone formation promoting effect on osteoblast cells. This investigation presents evidence that strontium promotes PDL cell proliferation. Simultaneously, strontium suppresses the expression of the inflammation-promoting cytokine IL-6. The observed effect of strontium on PDL cells supports its use it in guided dental tissue regeneration. PMID- 22051239 TI - Sialylated glycans and mucins in the lacrimal gland and eyelid of man and pig. Potential receptors for pathogenic microorganisms. AB - The conjunctiva of the eyelid is coated by secretion products from the lacrimal and eyelid glands, and by mucins produced by conjunctival goblet cells, which together form a glycoprotein-rich layer that lubricates and protects the surface of the eye. However, these ocular carbohydrates may also act as adhesives for viruses and bacteria and thereby facilitate their colonization. This paper provides histochemical demonstration of the in situ localization of such carbohydrate receptors in the form of sialylated glycans and mucins in the lacrimal and eyelid glands and conjunctiva from both humans and pigs. The pig is included in this study because viruses of swine origin may be capable of transmission to humans. We found that the human and pig ocular surfaces contain receptors for bacteria and viruses in the form of mucins (both membrane bound and secreted) and carbohydrates terminating in Sialylalpha2-6Gal epitopes and to a lesser degree in Sialylalpha2-3Gal. The glycosylation of the human soft palate could indicate a mucinous route for the spread of microorganisms from the eye via the nasolacrimal duct to the nasopharynx and thus to the upper part of the respiratory tract. PMID- 22051240 TI - Society of interventional radiology position statement: mini training courses in interventional radiology techniques. PMID- 22051241 TI - A prospective study of social difficulties, acculturation and persistent depression in Pakistani women living in the UK. AB - BACKGROUND: The reasons for the high prevalence of depressive disorders in women of Pakistani origin living in the UK are not clear. The aim of this study was to determine the relative importance of life events, chronic social difficulties and acculturation in a population-based sample of British Pakistani women. METHOD: A cross-sectional and prospective cohort study of 18- to 65-year-old Pakistani women in UK was carried out. The Schedule for Clinical Assessment in Neuropsychiatry for diagnosis, the Life Events and Difficulties Schedule for social stress and an acculturation questionnaire were used. RESULTS: Depressive disorder at baseline was associated with older age, social isolation and marked difficulties involving health and close relationships. Depressive disorder at follow-up was associated with severity of depression at baseline, difficulties in close relationships and two aspects of acculturation, especially less acculturation in relation to use of the English language. CONCLUSIONS: Lack of acculturation, especially less familiarity with the English language, is an independent predictor of persistence of depression in Pakistani women in UK. This needs to be taken into consideration when planning treatment, which also needs to address the personal difficulties associated with persistent depression. The implication of this work is that women of Pakistani origin with depression should be encouraged to receive help in the use of English as one part of treatment that may prevent relapse. PMID- 22051242 TI - mIGF-1/JNK1/SirT1 signaling confers protection against oxidative stress in the heart. AB - Oxidative stress contributes to the pathogenesis of aging-associated heart failure. Among various signaling pathways mediating oxidative stress, the NAD(+) dependent protein deacetylase SirT1 has been implicated in the protection of heart muscle. Expression of a locally acting insulin-like growth factor-1 (IGF-1) propeptide (mIGF-1) helps the heart to recover from infarct and enhances SirT1 expression in cardiomyocytes (CM) in vitro, exerting protection from hypertrophic and oxidative stresses. To study the role of mIGF-1/SirT1 signaling in vivo, we generated cardiac-specific mIGF-1 transgenic mice in which SirT1 was depleted from adult CM in a tamoxifen-inducible and conditional fashion. Analysis of these mice confirmed that mIGF-1-induced SirT1 activity is necessary to protect the heart from paraquat (PQ)-induced oxidative stress and lethality. In cultured CM, mIGF-1 increases SirT1 expression through a c-Jun NH(2)-terminal protein kinase 1 (JNK1)-dependent signaling mechanism. Thus, mIGF-1 protects the heart from oxidative stress via SirT1/JNK1 activity, suggesting new avenues for cardiac therapy during aging and heart failure. PMID- 22051243 TI - Diagnostic accuracy of probe-based confocal laser endomicroscopy in detecting residual colorectal neoplasia after EMR: a prospective study. AB - BACKGROUND: Residual neoplasia after EMR of colorectal lesions is common. There is a critical need for imaging methods to accurately diagnose residual disease and to guide retreatment in real time. OBJECTIVE: The aim was to estimate and compare the accuracy of virtual chromoendoscopy (VCE) and probe-based confocal laser endomicroscopy (pCLE) for detection of residual neoplastic tissue at the site of prior EMR. DESIGN: Prospective, blind, pilot comparison of advanced endoscopic imaging (VCE and pCLE) by using matching histology as reference standard. SETTING: Three tertiary-care referral hospitals. PATIENTS: This study involved 92 participants who underwent follow-up colonoscopies for the evaluation of prior EMR sites within 1 year. INTERVENTION: The EMR scars were assessed during follow-up high-resolution colonoscopy by using VCE (narrow-band imaging/Fujinon Intelligent Color Enhancement [FICE]), and pCLE. Confocal videos of EMR scars were interpreted in real time and were also stored and reviewed offline, blinded to histopathology and endoscopic appearance. Tissue confirmation by biopsies or polypectomy/repeat EMR was performed in all cases. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, and accuracy for VCE and pCLE alone and in combination against histopathology as the standard reference standard. RESULTS: Among 129 EMR scars, residual neoplasia was confirmed by histology in 29 sites (22%). For VCE, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 72%, 77%, 49%, 91%, and 77%, respectively, and were 97%, 77%, 55%, 99%, and 81% for pCLE (P = .045 for sensitivity). When only EMR scars for which VCE and pCLE agreed on the diagnosis were analyzed (95/129 scars), the accuracy, sensitivity, specificity, PPV, and NPV of pCLE and VCE were 90%, 100%, 87%, 67%, and 100%, respectively. LIMITATIONS: Small sample size, lack of power, involvement of highly experienced pCLE experts. CONCLUSION: Confocal endomicroscopy significantly increases the sensitivity for detecting residual neoplasia after colorectal EMR compared with endoscopy alone. When confocal endomicroscopy is used in combination with VCE, the accuracy is extremely high, and sensitivity approaches that of histopathology. Together, they may reduce the need for histologic examination and allow a highly accurate on-table decision to treat again or not, thus avoiding unnecessary repeat procedures. ( CLINICAL TRIAL REGISTRATION NUMBER: 00874263.). PMID- 22051244 TI - Poly(ADP-ribose)polymerase-1 modulates microglial responses to amyloid beta. AB - BACKGROUND: Amyloid beta (Abeta) accumulates in Alzheimer's disease (AD) brain. Microglial activation also occurs in AD, and this inflammatory response may contribute to disease progression. Microglial activation can be induced by Abeta, but the mechanisms by which this occurs have not been defined. The nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) regulates microglial activation in response to several stimuli through its interactions with the transcription factor, NF-kappaB. The purpose of this study was to evaluate whether PARP-1 activation is involved in Abeta-induced microglial activation, and whether PARP-1 inhibition can modify microglial responses to Abeta. METHODS: hAPP(J20) mice, which accumulate Abeta with ageing, were crossed with PARP-1(-/-) mice to assess the effects of PARP-1 depletion on microglial activation, hippocampal synaptic integrity, and cognitive function. Abeta peptide was also injected into brain of wt and PARP-1(-/-) mice to directly determine the effects of PARP-1 on Abeta induced microglial activation. The effect of PARP-1 on Abeta-induced microglial cytokine production and neurotoxicity was evaluated in primary microglia cultures and in microglia-neuron co-cultures, utilizing PARP-1(-/-) cells and a PARP-1 inhibitor. NF-kappaB activation was evaluated in microglia infected with a lentivirus reporter gene. RESULTS: The hAPP(J20) mice developed microglial activation, reduced hippocampal CA1 calbindin expression, and impaired novel object recognition by age 6 months. All of these features were attenuated in hAPP(J20)/PARP-1(-/-) mice. Similarly, Abeta(1-42) injected into mouse brain produced a robust microglial response in wild-type mice, and this was blocked in mice lacking PARP-1 expression or activity. Studies using microglial cultures showed that PARP-1 activity was required for Abeta-induced NF-kappaB activation, morphological transformation, NO release, TNFalpha release, and neurotoxicity. Conversely, PARP-1 inhibition increased release of the neurotrophic factors TGFbeta and VEGF, and did not impair microglial phagocytosis of Abeta peptide. CONCLUSIONS: These results identify PARP-1 as a requisite and previously unrecognized factor in Abeta-induced microglial activation, and suggest that the effects of PARP-1 are mediated, at least in part, by its interactions with NF kappaB. The suppression of Abeta-induced microglial activation and neurotoxicity by PARP-1 inhibition suggests this approach could be useful in AD and other disorders in which microglial neurotoxicity may contribute. PMID- 22051245 TI - Relative incidence of ESRD versus cardiovascular mortality in proteinuric type 2 diabetes and nephropathy: results from the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database. AB - BACKGROUND: Previous studies have shown that patients with chronic kidney disease, including those with diabetic nephropathy, are more likely to die of cardiovascular disease than reach end-stage renal disease (ESRD). This analysis was conducted to determine whether ESRD is a more common outcome than cardiovascular death in patients with type 2 diabetic nephropathy, significant proteinuria, and decreased kidney function who were selected for participation in a clinical trial. STUDY DESIGN: Retrospective analysis of the DIAMETRIC (Diabetes Mellitus Treatment for Renal Insufficiency Consortium) database derived from 2 prospective randomized controlled clinical trials (IDNT [Irbesartan Diabetic Nephropathy Trial] and RENAAL [Reduction of Endpoints in Non-Insulin-dependent Diabetes With the Angiotensin II Antagonist Losartan]). SETTING & PARTICIPANTS: 3,228 adult patients with type 2 diabetic nephropathy from IDNT and RENAAL were combined to establish the DIAMETRIC database. This is the largest global source of clinical information for patients with type 2 diabetic nephropathy who have decreased kidney function and significant proteinuria. INTERVENTION: Angiotensin receptor blocker versus non-angiotensin receptor blocker therapy to slow the progression of type 2 diabetic nephropathy (in the prospective trials). OUTCOMES & MEASUREMENTS: Incidence rates of ESRD, cardiovascular death, and all-cause mortality. RESULTS: Mean follow-up was 2.8 years; 19.5% of patients developed ESRD, approximately 2.5 times the incidence of cardiovascular death and 1.5 times the incidence of all-cause mortality. ESRD was more common than cardiovascular death in all subgroups analyzed with the exception of participants with low levels of albuminuria (albumin excretion <1.0 g/g) and well-preserved levels of kidney function (estimated glomerular filtration rate >45 mL/min/1.73 m(2)) at baseline. LIMITATIONS: All participants were included in a prospective clinical trial. CONCLUSIONS: Patients with type 2 diabetic nephropathy, characterized by decreased kidney function and significant proteinuria, are more likely to reach ESRD than die during 3 years' mean follow-up. Given the rapidly increasing number of cases of type 2 diabetes worldwide, this has implications for predicting future renal replacement therapy requirements. PMID- 22051246 TI - In situ randomised trial investigating abrasive effects of two desensitising toothpastes on dentine with acidic challenge prior to brushing. AB - OBJECTIVES: To determine if brushing dentine with 2 moderate RDA desensitising toothpastes, results in a significant dentine wear difference and whether this difference continues to be relevant when preceded with an erosive challenge. METHODS: An in situ, single centre, single blind, randomised, split mouth study, evaluated the difference in abrasion of 2 toothpastes (SFM - Sensodyne Fresh Mint((r)) RDA 70; CPHM - Crest Pro-Health Clean Mint((r)) RDA 120) in 28 healthy volunteers. Two toothpaste treatments were administered 3*/day, for each of the two 15 day periods, subjects wearing bi-lateral, lower buccal appliances each with 4 dentine sections. A 2 min extra-oral acidic challenge preceded toothbrushing for 2 study arms. Contact profilometry measured samples at baseline, days 5, 10 and 15. RESULTS: Brushing with SFM was significantly less abrasive than brushing with CPHM at all time points, with or without a preceding acidic challenge (p<0.0001). The additional dentine loss arising from the erosive challenge prior to brushing with each paste was linear with time and independent of abrasive effect. CONCLUSIONS: The desensiting toothpastes' RDA, directly related to dentine loss with toothbrushing. An acidic challenge prior to brushing did not negate the benefits of reduced wear from the lower RDA paste compared to the higher RDA paste. When brushing eroded dentine, the additional wear appeared independent of abrasive effect. Dentine hypersensitivity sufferers should be recommended to use a low-moderate RDA toothpaste, not to brush more than 2*/day and not immediately following an acidic challenge. PMID- 22051247 TI - Split-thickness skin graft donor site management: a randomized controlled trial comparing polyurethane with calcium alginate dressings. AB - Split-thickness skin grafting (SSG) is a common reconstructive technique for the treatment of patients with deep burns and other traumatic injuries. The management of the donor site after harvesting an SSG remains controversial because of a variety of dressings available for use. The aim of this randomized controlled trial was to compare the effectiveness of a polyurethane dressing, AllevynTM, to a calcium alginate, Kaltostat(r). From August 2009 to April 2010, 36 patients were randomized to AllevynTM or Kaltostat(r) for donor site management following split skin graft surgery. Pain intensity and adverse events were the primary outcomes assessed. Secondary outcome measures included time for wound healing, ease of application and removal and overall patient satisfaction. Time to first dressing change was earlier in those randomized to AllevynTM compared with Kaltostat(r) (5.5 days versus 8.11 days, P = 0.014). In patients randomized to AllevynTM, excessive exudate lead to a significantly increased number of dressing changes before day 10 (14 days versus 7 days, P = 0.018). The total number of dressing changes applied was also greater in those with AllevynTM compared with Kaltstat(r) (P = 0.007). There were no significant differences between the two treatment groups with respect to time to wound healing, level of pain intensity, length of stay, staff and patient satisfaction levels. This trial showed AllevynTM to be associated with increase demands on nursing time, increased cost of dressing products, medical consumables and wastes. Kaltostat(r) remains the dressing of choice for initial donor site dressing in this burns unit. PMID- 22051248 TI - Characteristics of patients presenting to the vascular emergency department of a tertiary care hospital: a 2-year study. AB - BACKGROUND: The structure of health care in Greece is receiving increased attention to improve its cost-effectiveness. We sought to examine the epidemiological characteristics of patients presenting to the vascular emergency department of a Greek tertiary care hospital during a 2-year period. We studied all patients presenting to the emergency department of vascular surgery at Red Cross Hospital, Athens, Greece between 1st January 2009 and 31st December 2010. RESULTS: Overall, 2452 (49.4%) out of 4961 patients suffered from pathologies that should have been treated in primary health care. Only 2509 (50.6%) needed vascular surgical intervention. CONCLUSIONS: The emergency department of vascular surgery in a Greek tertiary care hospital has to treat a remarkably high percentage of patients suitable for the primary health care level. These results suggest that an improvement in the structure of health care is needed in Greece. PMID- 22051249 TI - Frozen elephant trunk technique for extensive chronic thoracic aortic dissection: is it the final answer? PMID- 22051250 TI - Should a Jehovah's Witness patient who faces imminent exsanguination be transfused? PMID- 22051251 TI - Baseline left ventricular volume and shape as determinants of reverse remodeling induced by surgical ventricular reconstruction. AB - BACKGROUND: Early postoperative data show that surgical ventricular reconstruction (SVR) induces reverse remodelling (RR) in dilated ischemic cardiomyopathy. The stability of these results at follow-up is debated. This retrospective study determined whether RR was stable at follow-up and the role, if any, of preoperative left ventricle volume and shape on SVR-induced changes. METHODS: The study group comprised 220 patients (age, 64 +/- 9 years) with an echocardiography study at baseline, discharge, and at follow-up. RR was defined as a reduction of left ventricular end-systolic volume index (ESVI) at follow-up exceeding 15% vs baseline. RESULTS: Reverse remodelling occurred in 162 patients (74%); the ESVI at follow-up in the remaining 58 (26%) was equal to or greater than at baseline (no-RR). At baseline, the no-RR patients had lower volumes and higher ejection fraction; at the 1-week post-SVR evaluation, all patients reached significant ESV reduction, but at follow-up, the no-RR patients had dilated and showed significantly higher volumes and lower ejection fraction vs patients with RR. New York Heart Association class improved in both groups (2.6 +/- 0.6 to 1.6 +/- 0.5 and 2.5 +/- 0.8 to 1.8 +/- 0.7, respectively, p = 0.0001). Baseline ESVI less than 73 mL/m(2), apical axis less than 4.35 cm, and conicity index less than 0.759 were predictors of no-RR. CONCLUSIONS: A relatively small ESVI and a more physiologic apical shape (conical) are predictors of no-RR after SVR. Despite lack of RR, the ESV at follow-up is not severely enlarged, which explains the good survival rate in these patients. PMID- 22051252 TI - Invited commentary. PMID- 22051253 TI - Invited commentary. PMID- 22051254 TI - Integrated thoracic residency program applicants: the best and the brightest? AB - BACKGROUND: Comparative data are lacking on the numbers and nature of applicants to North American 6-year integrated thoracic residency and traditional thoracic fellowship programs. METHODS: Candidates applying within the first 3 months of the application cycles to the integrated and traditional thoracic surgery residency programs starting in 2011 at Mount Sinai Medical Center, New York, were reviewed. RESULTS: The overall ratio of applicants to positions was 27:1 for the traditional program and 131:1 for the integrated program. There was no significant difference in the proportion of female applicants (22% vs 16%, p = 0.57). Almost half of integrated program applicants were final-year medical students, 20% of whom attended institutions with integrated programs. Traditional program applicants on average had 4 years surgery residency experience compared with the average of 3 years reported by the 46% of applicants to the integrated program who had postgraduate clinical experience. More than half of integrated program applicants were overseas graduates. Shortlisted integrated applicants had significantly greater United States Medical Licensing Examination scores and peer reviewed publications than shortlisted traditional applicants and were more likely to hold higher degrees and national research funding. CONCLUSIONS: Much of the dramatic increase in the number of applicants to North American integrated thoracic residency programs has been driven by experienced international graduates. The caliber of applicants is strong, but efforts are needed to increase the appeal of thoracic surgery training to North American medical students if the goals of integrated programs are to be realized. PMID- 22051255 TI - Invited commentary. PMID- 22051256 TI - Lessons learned from experience with over 100 consecutive HeartMate II left ventricular assist devices. AB - BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) such as the HeartMate II have become the therapy of choice in patients with end-stage heart failure. The aim of this study is to report the outcomes in patients receiving the HeartMate II LVAD at a single center and review the lessons learned from this experience. METHODS: From June 2005 to June 2010, 130 consecutive patients received the HeartMate II LVAD. Of these, 102 were bridge-to-transplant (BTT), 17 destination therapy, and 11 exchanges for failed HeartMate XVE. This study focuses on the 102 BTT patients. The HeartMate II was approved by the US Food and Drug Administration (FDA) as BTT in April 2008 and 64 patients received this device as BTT since that date. We review our experience with the device as BTT and report on patient survival and adverse events as well as the impact of FDA approval on outcomes. RESULTS: Overall, mean age was 52.6 +/- 12.8 years; 26 (25.5%) were female. Disease etiology was ischemic in 58, nonischemic in 36, and other in 8. Overall, 30-day, 6-month, and 1-year survival for the BTT patients was 95.1%, 83.5%, and 78.8%, respectively. The 6-month survival in 38 patients in the clinical trial (pre-FDA) was 88.8% and was not statistically significant compared with the 76.2% 6-month survival in the 64 patients in the post-FDA approval period (p value = 0.1). Major adverse events among the 102 BTT patients included right ventricular failure in 5 (4.9%), LVAD driveline infections in 25 (24.5%), neurologic events in 10 (9.8%), and gastrointestinal bleeding in 18 (17.6%) patients. In addition, 1 patient (0.98%) had pump thrombus requiring device replacement. CONCLUSIONS: Despite significant morbidity, use of the HeartMate II LVAD as BTT provides excellent hemodynamic support and is associated with excellent survival and low mortality. In addition, there needs to be improvement and focused strategies in the areas of gastrointestinal bleeding, driveline infections, and adverse neurologic events for these devices to be able to provide a real long-term alternative to heart transplantation. PMID- 22051257 TI - Predictors of mortality after short-term ventricular assist device placement. AB - BACKGROUND: Risk assessment prior to long-term ventricular assist device (VAD) placement has been shown to be crucial for successful outcomes and efficient resource utilization. Short-term VADs are often used as salvage therapy in acute heart failure when the clinical scenario precludes such thorough preoperative assessment. Our goal was to devise a risk stratification system that may be used shortly after stabilization of hemodynamics with a short-term VAD to predict the likelihood of survival. METHODS: A retrospective study was performed of all patients undergoing Abiomed (Abiomed Cardiovascular Inc., Danvers, MA) or CentriMag (Levitronix LLC, Waltham, MA) placement at our institution or transferred to our institution with the device in place. From January 2001 until August 2009, 93 patients were identified. Preoperative and early postoperative variables were analyzed for their correlation with in-hospital mortality. RESULTS: Multivariable logistic regression analysis identified factors that were associated with death. A three-point scoring system, utilizing a diagnosis of postcardiotomy shock or graft failure, female sex, and postoperative day 3 total bilirubin greater than 5.2 mg/dL was devised. A score of 2 or greater was associated with an 86% mortality rate, whereas a score of 0 was associated with a 13% mortality rate. CONCLUSIONS: A simple scoring system based on readily available data may predict mortality after short-term VAD placement. Such a scoring system may be of prognostic value for physicians and patient families early in the support period and may help guide decisions. PMID- 22051258 TI - Invited commentary. PMID- 22051259 TI - Foldoplasty: a new and simplified technique for mitral valve repair that produces excellent medium-term outcomes. AB - BACKGROUND: Quadrangular resection with sliding valvuloplasty is the most common technique used to repair the posterior leaflet of the prolapsed mitral valve. Folding valvuloplasty is a simplified repair that does not involve resection and reduces the effective height of the posterior leaflet. We describe medium-term outcomes of patients who underwent folding valvuloplasty at our institution. METHODS: From 2002 to 2010, 161 patients underwent folding valvuloplasty at our institution. The primary endpoints in our study of these patients' medium-term outcomes included survival, freedom from reoperation, and echocardiographic evidence of recurrent mitral regurgitation (MR). RESULTS: The patients' median age was 61 +/- 14 years, 68 of the patients (42%) were male, and 146 of the patients (90%) had more than moderate to severe MR. Cardiopulmonary bypass and cross-clamp times were 117 +/- 40 minutes and 83 +/- 29 minutes, respectively. In addition to folding valvuloplasty, mitral rings with a median size of 38 mm (interquartile range, 34 mm to 38 mm) were used in 155 (96%) of the patients. One patient died during surgery. Medium-term follow-up data were available for all of the patients at a mean of 3.0 +/- 1.9 years after folding valvuloplasty. The patients' mean New York Heart Association class decreased significantly, from 2.0 +/- 0.9 to 1.1 +/- 0.4 (p < 0.0001), from the time of valvuloplasty to their mean medium-term follow-up evaluation. Two patients required reoperative mitral valve repair in the follow-up period. Postoperative echocardiograms were obtained for 142 (88%) patients at a mean of 1.6 +/- 1.2 years after valvuloplasty. The patients' mean grade of MR decreased significantly from the time of valvuloplasty to the time of mean medium-term follow up, from 3.8 +/- 0.5 (severe) to 0.8 +/- 0.8 (trace-mild) (p < 0.0001), with only five patients (3%) having moderate MR at follow-up. CONCLUSIONS: Folding valvuloplasty is durable and provides excellent structural and symptomatic results in patients with mitral prolapse. Given the ease and reproducibility of this technique, it should be offered as a suitable alternative to quadrangular resection for repair of the posterior leaflet in mitral prolapse. PMID- 22051260 TI - Invited commentary. PMID- 22051261 TI - Midterm outcome of valve-sparing aortic root replacement in inherited connective tissue disorders. AB - BACKGROUND: This study determined the midterm outcome of valve-sparing aortic root replacement for patients with inherited connective tissue disorders. METHODS: From 1993 to 2008, 94 patients underwent valve-sparing aortic root replacement. Sixty patients (64%), average age 33 years (range, 15 to 61 years), had inherited connective tissue disorders: Marfan syndrome, 54 (92%); Loeys-Dietz syndrome, 5 (8%); and smooth muscle alpha-actin (ACTA2) mutation in 1. Median preoperative sinus diameter was 52 mm (range, 42 to 76 mm), and moderate/severe aortic regurgitation was present in 14 (23%). Seven (12%, 1993 to 1999) underwent remodeling procedures, and 53 had reimplantation procedures. Cusp repair was performed in 4. Median follow-up was 55 months (range, 1 to 149 months). There were 15 patients in the early term (1993 to 2000) and 45 in the late term (2001 to 2008). RESULTS: Four late deaths occurred (cardiac, 3; aortic, 1), with 10 year survival of 86%. Rates of freedom from aortic valve replacement at 5 and 10 years were 85% and 58% in remodeling and 96% and 58% in reimplantation. Risk factors for reoperations were postprocedure intraoperative aortic insufficiency greater than mild (p = 0.046), remodeling procedure (p = 0.016), and early term (p = 0.0002). One patient (2%) with none/trivial postprocedure aortic insufficiency required aortic valve replacement. Freedom from reoperation in patients with none/trivial postprocedure aortic insufficiency at 5 and 10 years was 100% and 67%. CONCLUSIONS: Meticulous control of aortic insufficiency during operation would bring favorable midterm durability in valve-sparing aortic root replacement using a reimplantation technique, even in patients with inherited connective tissue disorders. PMID- 22051262 TI - Invited commentary. PMID- 22051263 TI - The frozen elephant trunk for the treatment of chronic dissection of the thoracic aorta: a multicenter experience. AB - BACKGROUND: Because of the extensive involvement of the aorta, surgical treatment of its chronic dissection continues to represent a surgical challenge. We conducted a study of a multicenter experience to describe a multicenter experience in the treatment of this complex pathology, using the frozen elephant trunk (FET) technique. METHODS: Between January 2005 and May 2010, 240 patients underwent treatment with the FET technique and had their clinical data collected in the International E-vita Open Registry. Ninety of the patients, who were the population in the present study, underwent operations for chronic dissection of the aorta (type A, 77%). The mean age of these 90 patients was 57 +/- 12 years, and 72 (80%) of the patients were male. Sixty-two patients (69%) had undergone a previous aortic operation. All of the procedures in the study were performed with the aid of antegrade selective cerebral perfusion. RESULTS: Total replacement of the aortic arch was done in 84 patients (93%). Cardiopulmonary bypass, myocardial ischemia, cerebral perfusion, and visceral ischemia times were 243 +/- 65, 145 +/ 48, 86 +/- 24, and 75 +/- 22 minutes, respectively. In-hospital mortality was 12% (11 patients). One patient died from a stroke and 8 patients (9%) died from ischemic spinal cord injury. The false lumen (FL) in the patients' aortae was evaluated with computed tomography after operation and during follow up. The rates of complete thrombosis of the FL around the elephant trunk were 69% and 79% at the first and last postoperative examinations, respectively. The rates of 4 year survival and freedom from aortic reoperation were 78% +/- 5% and 96% +/- 3%, respectively. CONCLUSIONS: The treatment of chronic aortic dissection (AD) with the FET technique is feasible, with respectable results. The rate of aortic reoperation with the use of this technique appears to be lower than that with a conventional approach to the repair of chronic AD. Ischemic spinal cord injury represents a concerning complication of the FET technique but seems to be unrelated to thrombosis of the FL. PMID- 22051264 TI - Transapical aortic valve implantation in high-risk patients with severe aortic valve stenosis. AB - BACKGROUND: Transapical aortic valve implantation (TA-TAVI) represents an alternative in patients with symptomatic severe aortic valve stenosis (SSAVS) who cannot be operated on or have a high surgical risk. The aim of this prospective multicenter observational study was to assess early and 2-year clinical and hemodynamic outcomes after TA-TAVI. METHODS: From May 2008 to September 2010, 179 patients with inoperable conditions or high-risk patients underwent TA-TAVI at 4 institutions. Indications for TA-TAVI were SSAVS and logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) greater than 20% or porcelain aorta in patients with severe aortoiliac disease. Patients underwent clinical and echocardiographic follow-up visits at hospital discharge, 3 and 6 months after TA TAVI, and every 6 months thereafter. The impact of the learning curve for the centers and of intraoperative complications on patient outcomes was also evaluated. RESULTS: Mean age was 81 +/- 6 years. Mean logistic EuroSCORE was 22% +/- 12%. Transapical delivery was successful in all patients. Seventeen severe intraoperative complications occurred in 13 (7.3%) patients. Thirty-day mortality was 3.9% (7 patients). Mean follow-up was 9.2 +/- 6.5 months. Late mortality occurred in 9 patients. Two-year survival was 88% +/- 3%. An intraoperative severe complication was identified as the only significant independent predictor of 1-year mortality. A significant benefit was found when comparing 2-year survival of the second versus the first 50% patients at each center (93% +/- 2% versus 84% +/- 3 %; p = 0.046). A significant reduction of both mean and peak gradients from the preoperative to the postoperative period, which remained stable during follow-up, was found. CONCLUSIONS: TA-TAVI provides excellent early and 2-year results in terms of survival, valve-related adverse events, and hemodynamic performance. Survival after TA-TAVI is affected by the center learning curve and by the occurrence of an intraoperative complication. PMID- 22051265 TI - Invited commentary. PMID- 22051266 TI - Critical analysis of early and late outcomes after isolated coronary artery bypass surgery in elderly patients. AB - BACKGROUND: The proportion of elderly (>=80 years) patients undergoing coronary artery bypass surgery (CABG) is increasing. METHODS: A retrospective analysis of data, collected by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program between June 2001 and December 2009 was performed. Isolated CABG was performed in 21,534 patients; of these, 1,664 (7.7%) were at least 80 years old (group 1). Patient characteristics, morbidity, and short-term mortality of these patients were compared with those aged less than 80 years (group 2). The long-term outcome of group 1 patients after CABG surgery was compared with an age and sex-matched Australian population. RESULTS: Patients over 80 years old were more likely to be female (36.6% vs 17.3%, p < 0.001) and presented significantly more often with heart failure, hypertension, and triple vessel disease (all p < 0.05). The 30-day mortality was higher in group 1 patients (4.2% vs 1.5%, p < 0.001). Group 1 patients also had an increased risk of complications, including prolonged (>24 hours) ventilation (14.2% vs 8.2%, p < 0.001), renal failure (7.3% vs 3.4%, p < 0.001), and mean intensive care unit stay (60.7 vs 42.5 hours, p < 0.001). The 5-year survival of elderly patients (73%) was comparable with the age-matched Australian population. Independent risk factors for 30-day mortality in group 1 patients included preoperative renal failure (p = 0.010), congestive heart failure (p = 0.014), and a nonelective procedure (p = 0.016). CONCLUSIONS: Elderly patients who undergo isolated CABG have significantly lower perioperative risks than have been previously reported. The long-term survival of these patients is comparable with an age-adjusted population. PMID- 22051267 TI - Invited commentary. PMID- 22051268 TI - Invited commentary. PMID- 22051269 TI - Invited commentary. PMID- 22051270 TI - Invited commentary. PMID- 22051271 TI - Long-term myocardial scarring after operation for anomalous left coronary artery from the pulmonary artery. AB - BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a very rare disease. Accordingly, the incidence and distribution of myocardial scarring in long-term follow-up of patients after successful surgery of ALCAPA is unknown. Therefore, the aim of this study was to describe the distribution of left ventricular (LV) myocardial scarring by late gadolinium enhancement magnetic resonance in these patients. METHODS: Fourteen consecutive patients over 12 years of age with ALCAPA without any further cardiac abnormalities, and after corrective surgery at our center, participated prospectively in this study. All patients underwent cardiac magnetic resonance including LV function analysis and late gadolinium enhancement magnetic resonance. Of these 14 patients, 12 patients also underwent cardiopulmonary exercise testing. RESULTS: Four patients had no evidence of myocardial scarring. The median extent of the myocardial scar of all patients by late gadolinium enhancement magnetic resonance, expressed as a percentage of the total LV myocardial volume, was only 2% (range, 0% to 11%). Median LV ejection fraction was 0.55 (range, 0.31 to 0.73). Median LV end diastolic volume indexed to body surface area was 84 mL/m(2) (39 to 120 mL/m(2)). Median peak oxygen uptake during cardiopulmonary exercise was 24 mL . kg(-1) . minute(-1) (range, 19 to 51 mL/kg/minute). CONCLUSIONS: We conclude that despite often severely compromised LV function and evidence of scarring before corrective surgery of patients with ALCAPA, in long-term follow-up scar tissue is relatively scarce. PMID- 22051272 TI - Invited commentary. PMID- 22051273 TI - Invited commentary. PMID- 22051274 TI - Pulmonary resection of metastatic sarcoma: prognostic factors associated with improved outcomes. AB - BACKGROUND: There are few data to predict the benefit of pulmonary metastasectomy in patients with extrathoracic sarcoma. This study analyzes prognostic factors associated with improved outcomes. METHODS: Between June 2002 and December 2008, 97 patients underwent pulmonary resection for metastatic sarcoma at Massachusetts General Hospital. Eight patients were excluded because of lack of follow-up data. Analysis was performed using Kaplan-Meier estimates of survival, log-rank test, and multivariate Cox model. RESULTS: Overall 5-year survival for the cohort was 50.1%. Patients who had multiple operations for recurrent pulmonary metastases had better 5-year survival compared with patients who had a single operation (69 versus 41%; p = 0.017). Median disease- free survival (DFS) for the reoperation group was 12.9 months compared with 9.1 months for the single-operation group (p < 0.028). Patients with a disease-free interval (DFI) greater than 12 months from detection of primary sarcoma to pulmonary metastasectomy had improved survival compared with those whose DFI was less than 12 months (p < 0.0001). Patients with bilateral metastasectomy had lower 5-year survival compared with metastasectomy for unilateral disease (22% versus 68% ;p < 0.0001). Two or more metastases were associated with poorer outcome compared with a single metastasis (p = 0.0007). A positive resection margin portended worse survival compared with a negative resection margin (p = 0.004). Patients with lesions larger than 3 cm had decreased survival compared with patients with lesions smaller than 3 cm (p = 0.017) with no difference in median DFS. Histologic type, grade of tumor, and use of chemotherapy had no effect on survival. Multivariate analysis showed that patients with a DFI greater than 12 months (p = 0.001), single-sided metastasis (p = 0.001), negative margins (p = 0.002), and multiple operations (p = 0.018) had better survival. CONCLUSIONS: Pulmonary metastasectomy for sarcoma can be associated with prolonged survival. Tumor resectability, DFI, number of metastases, and laterality are important factors in determining patient selection for curative surgical intervention. Repeated pulmonary metastasectomy in select patients may improve survival despite recurrent disease. PMID- 22051275 TI - Epithelial to mesenchymal transition is a determinant of sensitivity to chemoradiotherapy in non-small cell lung cancer. AB - BACKGROUND: The epithelial to mesenchymal transition (EMT) is a fundamental biological process during which epithelial cells change to a mesenchymal phenotype; it has a profound impact on cancer progression. The purpose of this study was to clarify the role of EMT in the sensitivity of non-small cell lung cancer (NSCLC) to chemoradiotherapy (CRT). METHODS: We evaluated the correlation between EMT and sensitivity to chemotherapy or radiotherapy using NSCLC cells induced to undergo EMT with epidermal growth factor or transforming growth factor beta1. Immunohistochemistry was used to examine the expression of EMT markers, E cadherin, cytokeratin, N-cadherin, and vimentin in 50 tumor specimens obtained from patients with NSCLC both before and after CRT. RESULTS: The EMT resulted in increased malignant potential and reduced sensitivity to cisplatin and paclitaxel in NSCLC cells. Furthermore, chronic exposure to cisplatin, paclitaxel, or radiation altered the cells into therapy-resistant sub-lines that showed phenotypic changes such as a spindle-cell shape and increased EMT marker expression. Also, decreased expression of epithelial markers and upregulation of mesenchymal markers were detected in surgically resected specimens after CRT compared with biopsy specimens obtained before treatment. The disease-free survival rate of patients with EMT marker-positive tumors was significantly lower than that of those with EMT marker-negative tumors. CONCLUSIONS: The EMT marker expression was detected in NSCLC tumors after CRT, indicating that EMT changes are associated with insensitivity to CRT. New therapeutic combinations using EMT signaling inhibitors may be needed to circumvent the resistance of some types of cancer to CRT. PMID- 22051276 TI - Invited commentary. PMID- 22051277 TI - Lobectomy versus sublobar resection for small (2 cm or less) non-small cell lung cancers. AB - BACKGROUND: We evaluated a cohort of patients who underwent resection for small (2 cm or less) non-small cell lung cancer (NSCLC) to determine if there is an association between extent of resection (lobar versus sublobar resection) and local recurrence or survival. METHODS: We reviewed 468 consecutive patients who underwent resection for small NSCLC at our institution between 2000 and 2005. We excluded patients who had neoadjuvant therapy, active noncutaneous malignancies, pure bronchioalveolar carcinoma, lymph node (n = 53) or distant metastases at diagnosis, or multicentric cancers. Clinicopathologic data, recurrence, and vital status as of June 15, 2010, were retrieved. Overall and recurrence-free survival from surgery rates were assessed. RESULTS: Two hundred thirty-eight patients underwent resection for primary solitary small NSCLC. Lobectomy (n = 84) was associated with longer overall (p = 0.0027) and recurrence-free (p = 0.0496) survival. Patients who underwent sublobar resection were older (p < 0.0001) and had worse pulmonary function (p < 0.0014). While there was a trend toward increased rate of local recurrence for sublobar resection (16% versus 8%, p = 0.1117), there was no difference in distant recurrence. Moreover, when lymph nodes were sampled with sublobar resection, local recurrence rate and overall and recurrence-free survival distributions were similar to those for lobectomy. CONCLUSIONS: Sublobar resection is reasonable in older patients with limited cardiopulmonary function. For healthy patients, however, lobectomy remains the standard therapy, with sublobar resection with lymph node sampling representing an alternative to consider. These findings support continued effort to conduct a randomized trial of lobar versus sublobar resection, such as CALGB 140503. PMID- 22051278 TI - Positron emission tomography-computed tomography for postoperative surveillance in non-small cell lung cancer. AB - BACKGROUND: The role of positron emission tomography-computed tomography (PET-CT) for the staging of non-small cell lung cancer (NSCLC) has been well documented, whereas its role for postoperative surveillance after the curative resection of this cancer has not. We prospectively implemented PET-CT in our surveillance protocol for recurrence of NSCLC and investigated its effectiveness as compared with that of conventional methods. METHODS: The cohort for our study of PET-CT in detecting recurrence of NSCLC consisted of 358 patients who had undergone complete resection of NSCLC between January 2005 and June 2008. After resection of their tumors, all of the patients were routinely examined at the thoracic surgical outpatient clinic at 3-month intervals for 2 years and after this at 6 month intervals for next 3 years. Careful patient interviews, physical examinations, chest roentgenography, and measurements of the serum carcinoembryonic antigen level were done at each visit. Contrast-enhanced chest CT was done at 6-month intervals, and PET-CT was done annually for 5 years after resection of NSCLC. RESULTS: Recurrences were detected in 111 patients (31%). In 60 of these patients, recurrence was detected with conventional methods, and in the remaining 51 patients recurrences were detected with simultaneous PET-CT and chest CT. Among these latter patients, recurrence was evident in both the chest CT and PET-CT scans of 26 patients (51.0%), and in the PET-CT scans alone of 19 patients (37.3%). Five lung lesions (2 small, 1 subpleural, 1 cavitary, and 1 nodule of ground-glass opacity) and 1 pancreatic metastasis were detected with chest CT only. CONCLUSIONS: When the two methods were used simultaneously, PET-CT seemed superior to chest CT for detecting recurrences of NSCLC. However, because PET-CT may fail to detect small or hypometabolic recurrences of NSCLC, we recommend that it be done on an annual basis along with low-dose chest CT. PMID- 22051279 TI - Adenosine A2A agonist improves lung function during ex vivo lung perfusion. AB - BACKGROUND: Ex vivo lung perfusion (EVLP) is a novel technique than can be used to assess and potentially repair marginal lungs that may otherwise be rejected for transplantation. Adenosine has been shown to protect against pulmonary ischemia-reperfusion (IR) injury through its A(2A) receptor. We hypothesized that combining EVLP with adenosine A(2A) receptor agonist treatment would enhance lung functional quality and increase donor lung use. METHODS: Eight bilateral pig lungs were harvested and flushed with cold Perfadex (Vitrolife, Englewood, CO). After 14 hours of storage at 4 degrees C, EVLP was performed for 5 hours on 2 explanted lung groups: (1) control group lungs (n = 4) were perfused with Steen Solution (Vitrolife) and dimethyl sulfoxide and (2) treated group lungs (n = 4) received 10 MUM CGS21680, a selective A(2A) receptor agonist, in a Steen solution primed circuit. Lung histologic features, tissue cytokines, gas analysis, and pulmonary function were compared between groups. RESULTS: Treated lungs demonstrated significantly less edema as reflected by wet-dry weight ratio (6.6 versus 5.2; p < 0.03) and confirmed by histologic examination. In addition, treated lung demonstrated significantly lower levels of interferon-gamma (IFN- gamma) (45.1 versus 88.5; p < 0.05). Other measured tissue cytokine levels (interleukin [IL]-1beta, IL-6, and IL-8) were lower in the treatment group, but values failed to reach statistical significance. The oxygenation index was improved in the treated group (1.5 versus 2.3; p < 0.01) as was mean airway pressure (10.3 versus 13; p < 0.009). CONCLUSIONS: Combined use of adenosine A(2A) agonist and EVLP significantly attenuates the inflammatory response in acutely injured lungs after IR and enhances pulmonary function. This combination may improve donor lung quality and could increase the donor lung pool for transplantation. PMID- 22051280 TI - Geographic distance between donor and recipient does not influence outcomes after lung transplantation. AB - BACKGROUND: The shortage in organ donation is a major limiting factor for patients with end-stage lung disease. Expanding the donor pool would be beneficial. We investigated the importance of geographic distance between the donor and recipient and hypothesized that it would not be a critical determinant of outcomes after lung transplantation. METHODS: We retrospectively reviewed the United Network for Organ Sharing lung transplant database from 2000 to 2005 to allow sufficient time for bronchiolitis obliterans syndrome (BOS) development. Allograft recipients were stratified by geographic distance from their donors (local, regional, and national) and had yearly follow-up. The primary end points were the development of BOS and 1-year and 3-year mortality. Posttransplant outcomes were compared using a multivariable Cox proportional hazard model. Kaplan-Meier curves were compared by log-rank test. RESULTS: Of 6,055 allograft recipients, donors were local in 59%, regional in 19.3%, and national in 21.7%. BOS-free survival did not differ by geographic distance. Geographic distance did not independently predict BOS (hazard ratio, 1.03; 95% confidence interval, 0.96 to 1.10). Similarly, Kaplan-Meier survival curves were not significantly worse for recipients with national donors. Geographic distance did not independently predict 3-year mortality (hazard ratio, 0.95; 95% confidence interval, 0.89 to 1.01). CONCLUSIONS: With appropriate donor selection, moderately long geographic distance (average ischemic time < 6 hours) between the donor and recipient is not associated with the development of BOS or increased death after lung transplantation. By placing less emphasis on distance, more donors could potentially be used to expand the donor pool. PMID- 22051281 TI - First experience with biodegradable airway stents in children. AB - PURPOSE: We here report our experience with biodegradable polydioxanone stents for tracheal narrowing in children. DESCRIPTION: Eleven custom-made polydioxanone stents were implanted in 4 patients with airway narrowing due to external compression or intrinsic collapse. The median stent diameter was 9 mm (range, 6 to 14 mm) and median length was 15 mm (range, 13 to 70 mm). EVALUATION: Narrowing was relieved initially in all cases. There was no bleeding or perforation after polydioxanone stent implantation. Size mismatching was a problem in 2 cases. Three patients needed repeat stenting after stent absorption. There was 1 death, unrelated to the stent implantation. All 3 survivors are in good clinical condition up to 12 months after first stenting. CONCLUSIONS: This pilot study shows that polydioxanone stents offer an alternative to metallic or silastic stents for collapse or external compression of the trachea in children. They may avoid the need for permanent stenting and allow subsequent growth of the airway. PMID- 22051282 TI - Intraoperative diagnosis of bilateral coronary ostia stenosis: a rare case of ischemic heart disease in a 3-month-old patient. AB - We report a case of a 3-month-old child, presenting with signs of myocardial ischemia and hemodynamic instability, requiring extracorporeal membrane oxygenation support. Due to the unclear preoperative instrumental findings, a surgical exploration was performed revealing the presence of coronary ostia stenosis and an intramural course of both coronary arteries. The child underwent a successful plasty of the coronary artery ostia by resecting the excessive obstructing fibrous tissue followed by unroofing of the intramural coronary artery course with restoring of a normal myocardial perfusion and function. PMID- 22051283 TI - Cardiac paraganglioma and gastrointestinal stromal tumor: a pediatric case of Carney-Stratakis syndrome. AB - The eponymous Carney triad reported the association of gastric leiomyosarcoma, also known as a gastrointestinal stromal tumor, extra-adrenal paraganglioma and pulmonary chondromata. Subsequently, Carney and Stratakis distinguished the inherited gastrointestinal stromal tumor with paraganglioma syndrome from the classical Carney Triad as an autosomal dominant condition in adult patients. This combination of gastrointestinal stromal tumor and cardiac paragangliomata in a child is almost unique. PMID- 22051284 TI - Aortic erosion during negative pressure therapy in a pediatric heart transplant recipient. AB - A happy-ending "series of unfortunate events" is reported of the successful emergency treatment of an erosion of the ascending aorta during negative pressure sternal wound therapy for a relapse of Berlin Heart driveline infection in a pediatric transplant recipient. Several key issues related to assist device related infections and negative pressure complications are discussed in this peculiar setting. PMID- 22051285 TI - Transcatheter self-expandable aortic valve implantation after undersized mitral annuloplasty. AB - No data are available in the literature regarding the effectiveness and safety of transcatheter aortic valve implantation in patients who underwent previous mitral valve ring repair. Concerns exist related to the possible interference between the percutaneous aortic valve and the mitral annuloplasty ring. We report our experience with percutaneous aortic self-expandable valve implantation in a 76 year-old woman affected by severe aortic stenosis, previously operated on for "undersized" mitral annuloplasty repair of severe functional mitral regurgitation in dilated cardiomyopathy. No deformation of the nitinol tubing of the CoreValve device (CoreValve, Inc, Irvine, CA), neither distortion nor malfunction nor change of the conformation of the mitral ring occurred. No change in mitral function and regurgitation was evident at echocardiography monitoring, which was performed during the implant. PMID- 22051286 TI - Spontaneous coronary artery dissection in Ehlers-Danlos syndrome. AB - Ehlers-Danlos syndrome is a heterogeneous group of connective tissue disorders with type IV, the vascular subtype, behaving as the most severe largely due to spontaneous arterial aneurysm and dissection. In this case report we describe a spontaneous left anterior descending coronary artery dissection treated with coronary artery bypass graft in a patient with Ehlers-Danlos syndrome type IV. PMID- 22051287 TI - Coronary artery spasm after Cryo Maze III procedure. AB - The Cox Maze III procedure has been simplified with the availability of tissue ablation devices; however, complications related to their use are recognized. We report a case of 45-year-old woman who underwent mitral valve repair and concomitant Cryo-Maze procedure. She had reversible right coronary artery spasm develop after the procedure demonstrated by ST-segment elevation changes and coronary angiography, which was reversed with intracoronary nitroglycerin. The region of spasm suggested it as a consequence of proximity of the right coronary artery to the right atrial ablation lines. PMID- 22051288 TI - Compression of an anomalous left circumflex artery after aortic and mitral valve replacement. AB - A 52-year-old gentleman with a history of rheumatic fever presented with dyspnea. Transthoracic echocardiography revealed severe valvular aortic stenosis and severe mitral stenosis. A preoperative coronary angiogram revealed an anomalous left circumflex (LCX) artery arising from the right coronary sinus. The patient underwent aortic and mitral valve replacement. Postoperatively, a non-ST segment elevation myocardial infarction developed, and coronary angiography confirmed subtotal occlusion of the anomalous LCX. An emergent reoperation with surgical revascularization was performed. Intraoperatively, the mechanism of injury to the LCX was determined to be compression of the distal LCX by the sewing ring of the two prosthetic valves. PMID- 22051289 TI - Successful reconstruction of sternum with a scapular autograft segment: 5-year follow-up. AB - Complete loss of the sternum after osteomyelitis leads to chest wall instability and decreases respiratory mechanics. Thus, surgical management with prosthetic devices or various flap coverage procedures is required to restore anterior chest wall stability. We report on a new technique of an osteocutaneous flap from the scapula providing thoracic stability and protective coverage of mediastinal organs, and additionally allowing removal of osteosynthesis material. A 5-year follow-up demonstrates excellent durability and outcome. PMID- 22051290 TI - Successful surgical treatment of a posttransplantation bronchovascular fistula involving the pulmonary vein. AB - Bronchovascular fistula is a rare complication after lung transplantation, which usually has a fatal outcome. We describe the case of successful surgical treatment of bronchovascular fistula of the left upper pulmonary vein and the left main bronchus. PMID- 22051291 TI - Proliferating bronchial webs after lung transplantation. AB - This case details the decline in lung function due to bronchial webs in a lung transplant recipient. The decline occurred 2 years after transplantation and, despite therapy, the webs, which had an inflammatory component, became treatment resistant. We outline the pathological findings and management strategies used, discuss the evidence in the literature, and offer possible causes for these unusual clinical findings. PMID- 22051292 TI - Transection of the aerodigestive tract after blunt neck trauma. AB - Survival after blunt neck trauma resulting in combined tracheal and esophageal injury is uncommon. We present the case of a young boy who sustained complete transection of the trachea and subtotal transection of the esophagus after a clothes line type injury. PMID- 22051293 TI - Metastasis of pleural mesothelioma presenting as bleeding colonic polyp. AB - We report the case of a 72-year-old woman with metastatic malignant mesothelioma presenting as right colonic polyp. She was diagnosed with malignant pleural mesothelioma 2 years previously and underwent surgery, radiotherapy, and chemotherapy. After 2 years with a negative follow-up, she was admitted to the infectious disease department for malaria and severe anaemia. A computed tomographic scan and a colonoscopy showed a huge bleeding polypoid lesion in the right colon diagnosed as adenocarcinoma. She underwent a right hemicolectomy; a pathologic examination found neoplastic cell population positive to anti cytokeratin7, anti-calretinin, anti-vimentin, and negative for anti-cytokeratin 20, MOC-31, and thyroid transcription factor 1, providing a diagnosis of metastatic mesothelioma. PMID- 22051294 TI - Fatal cerebral air embolus complicating multimodality treatment of esophageal cancer. AB - A 38-year-old woman with clinical T3N1M0 esophageal adenocarcinoma received an institutional protocol of induction chemotherapy, esophagectomy, and consolidation chemoradiotherapy. Three months after treatment, she had an acute mental status change develop and grand mal seizures. Intracranial imaging demonstrated massive cerebral air emboli, and a rapidly fatal neurologic deterioration ensued. At autopsy, a nonmalignant 0.5-cm gastric conduit to the left atrial fistula was identified. This case illustrates a rare, but fatal, late benign complication of aggressive therapy for locally advanced esophageal cancer. PMID- 22051295 TI - An unusual mediastinal mass. PMID- 22051296 TI - Refractory bilateral pneumothoraces in end-stage cystic fibrosis. PMID- 22051297 TI - Late complication of a silastic prosthetic correction of pectus excavatum. PMID- 22051298 TI - Total cavopulmonary connection with innovative combined lateral tunnel and extracardiac conduit in heterotaxy syndrome. AB - Total cavopulmonary connection remains a challenging procedure when treating heterotaxy syndrome patients with a widely separate drainage of the inferior vena cava and the hepatic vein into the common atrium. We trimmed a Gore-Tex tube graft (W.L. Gore & Associates, Flagstaff, AZ) to form a skirt to cover both openings of the inferior vena cava and the hepatic vein. This tubular structure pierces the atrium and travels outside the heart, and then reaches the inferior side of the pulmonary artery to avoid pulmonary vein obstruction. We then sutured the pierced atriotomy margin to the conduit. This innovative procedure has been shown to accommodate the widely separated hepatic vein drainage with a promising outcome. PMID- 22051299 TI - Transapical valve implantation and resuscitation: risk of valve destruction. AB - In this article we illustrate our experience with the destruction of a transapically implanted aortic valve prosthesis due to postoperative cardiopulmonary resuscitation. The fact of the existing risk of the valve damage by chest compression during cardiopulmonary resuscitation should be taken into consideration when discussing the potential exposure of this technology to lower the risk for patients. Furthermore, we introduce a technique of less invasive cardiopulmonary resuscitation that offers the possibility of lowering the risk of compressing the valve. PMID- 22051300 TI - Staged resternotomy for a retrosternal giant aneurysm of the thoracic aorta using an inferior T-shaped ministernotomy. AB - We describe a staged resternotomy technique using an inferior T-shaped ministernotomy for three redo cases with a retrosternal aortic arch aneurysm. To minimize the disadvantages of resternotomy during closed-chest hypothermia, an inferior T-shaped ministernotomy was performed before approaching the aneurysm. After establishment of the cardiopulmonary bypass with femoral or axillary arterial cannulation, or both, and right atrial drainage, a venting catheter was inserted into the left ventricle and core cooling was induced at 25 degrees C. The retrosternal aneurysm was then exposed by additional superior sternotomy. Under hypotherma with antegrade cerebral perfusion, the distal side of a four branched graft was anastomosed. During rewarming, reconstruction of the arch vessels and proximal anastomosis of the branched graft were performed. In the 3 patients operated on using this technique, there were no perioperative deaths or serious complications. This suggests that the technique can be safely performed and minimizes the disadvantages of the widely used resternotomy technique. PMID- 22051301 TI - A new proximal anastomosis technique in two patients with severely calcified aorta. AB - A severely calcified aorta carries a high risk of atheroemboli and bleeding for cardiac surgery with an incidence range of 14% to 29%. Various techniques were described avoiding cannulation and clamping of the aorta. Nowadays, the no-touch beating heart technique seems to be the best alternative in patients with calcific aorta. Herein, we present a closed proximal anastomosis technique in this high-risk patient group. PMID- 22051302 TI - Suturing of penetrating wounds to the heart in the nineteenth century: the beginnings of heart surgery. AB - The beginnings of cardiac surgery go back to the 19th century. This article describes the history of the first attempts to operate on the heart. In 1882, Dr Block from Danzig, and in 1895, Simplicio Del Vecchio, published reports of animal experiments showing that the suturing of heart wounds is possible. After unsuccessful attempts by Axel Cappelen in Norway and Guido Farina in Italy, it was Ludwig Rehn of Germany who first sutured a laceration of the right ventricle of a human heart. Shortly afterward, Antonio Parrozzani successfully sutured a stab wound of the left ventricle. Following cardiac surgery back to its very beginnings, it is striking that the first attempts in the 19th century to repair the injured heart were regarded with great skepticism, and that heart suturing only slowly became an established method of treatment. Once the concept of cardiac surgery had become accepted, however, many kinds of operations were developed, paving the way for an explosion in the number of cardiac operations, as we well know, in the century that followed. PMID- 22051303 TI - Effects of blood conservation on perioperative CABG outcomes. PMID- 22051305 TI - When is the optimal time to perform neurocognitive assessment after coronary artery bypass surgery? PMID- 22051307 TI - Combined use of the Iida device and the "loop" technique in mitral neochordal construction. PMID- 22051309 TI - Freedom solo stentless aortic valve: quantitative and qualitative assessment of thrombocytopenia. PMID- 22051310 TI - Are transcatheter aortic valve implantations cost-effective in the management of patients with aortic stenosis? PMID- 22051311 TI - Pathophysiology of pneumopericardium after blunt thoracic trauma. PMID- 22051313 TI - Extracorporeal membrane oxygenation as a bridge to pulmonary endarterectomy. AB - Untreated severe chronic thromboembolic pulmonary hypertension has a poor prognosis ending with right heart decompensation and multiorgan failure. This case report demonstrates that it is possible to intervene in the terminal stages of chronic thromboembolic pulmonary hypertension and bridge patients to surgery and recovery using various forms of extracorporeal membrane oxygenation support. PMID- 22051314 TI - Stent angioplasty for a kink in the pulmonary artery anastomosis soon after living-donor lobar lung transplantation. AB - Herein, we report a case of stent angioplasty for a kink in the pulmonary artery (PA) anastomosis soon after living-donor lobar lung transplantation (LDLLT). A 64 year-old man with idiopathic pulmonary fibrosis underwent bilateral LDLLT with lung donations from his daughters. After reperfusion, the left PA anastomosis showed a kink, which could not be corrected completely during surgery. Due to the kink in the left PA, and the relatively small donor grafts, the patient required extracorporeal membrane oxygenation) after LDLLT. Approximately 24 hours after reperfusion, stent angioplasty was performed, resulting in the patient being successfully weaned from extracorporeal membrane oxygenation on postoperative day 4. PMID- 22051315 TI - Nonsymptomatic tracheocele-like sac after tracheoesophageal fistula repair. PMID- 22051316 TI - Multiple cystic pulmonary amyloidosis. PMID- 22051317 TI - Tracheal reconstruction using S-shaped skin flaps and a conchal cartilage graft. AB - We have devised a technique of two-stage tracheal reconstruction using S-shaped skin flaps and an aural conchal cartilage graft. During the first operation, S shaped skin flaps were elevated before resection of the trachea. A tracheocutaneous fistula was created at the tracheal defect using S-shaped skin flaps while placing the conchal cartilage graft underneath. During the second operation, a skin incision was made around the fistula to elevate the hinge flaps, including the cartilage. The edges of the hinge flaps were sutured to form the tracheal lumen, and the area of the skin defect was then closed with double rotation skin flaps. PMID- 22051318 TI - Long-term survival of salvage cardiac transplantation for infective endocarditis. AB - Cardiac transplantation has been rarely performed in patients with infective endocarditis. A 31-year-old man developed aortic endocarditis due to Brucella melitensis. He presented with fever and developed acute myocardial infarct, severe aortic regurgitation, and heart failure. Aortic valve replacement did not improve cardiac function; hence, an emergent cardiac transplantation was carried out. Eighteen years later, he is doing well and living an active and productive life. Only 6 patients have received a cardiac transplant as part of the treatment of active infective endocarditis. This patient shows how cardiac transplantation may be successfully used as salvage therapy for patients with infective endocarditis who are not candidates for valve replacement or have severe and irreversible myocardial damage. PMID- 22051319 TI - Embol-X intraaortic filter and transaortic approach for improved cerebral protection in transcatheter aortic valve implantation. AB - Techniques for transcatheter aortic valve implantation involve manipulation of the native aortic valve and the aortic arch. As a result, excellent technical outcomes of this technique remain counterbalanced by a level of neurologic complications that remain unacceptably high. We present here a report of a new potential combined approach to reduce periprocedural neurologic events. After a 6 cm J-shaped upper-mini-sternotomy, 26-mm Sapien valve (Edwards Lifesciences, Irvine, CA) was deployed through a transaortic approach. In addition, the Embol-X device (Edwards Lifescience) was directly inserted in the distal ascending aorta was deployed during all the procedure. Postoperative evolution was clinically uneventful. Postoperative magnetic resonance imaging revealed no new ischemic lesions in this first patient. PMID- 22051320 TI - Rupture of a left sinus of valsalva aneurysm with coronary compression: a rare cause of ischemic chest pain. AB - We describe the case of a 52-year-old man presenting with chest pain and ischemic electrocardiogram changes. He was initially prepared to undergo primary percutaneous intervention, but echocardiography revealed pericardial effusion and computed tomography confirmed the diagnosis of rupture of a left sinus of Valsalva aneurysm. Emergency surgery was performed, and the aneurysm was repaired using a composite Dacron-Aortic homograft patch. The patient had a good postoperative recovery. This case report demonstrates the difficulty dealing with the minority of patients presenting with presumed ST elevation myocardial infarction, but for whom the life-saving treatment is surgery. PMID- 22051321 TI - Characterization of Paralichthys olivaceus peroxisome proliferator-activated receptor-alpha gene as a master regulator of flounder lipid metabolism. AB - Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that play key roles in lipid and energy homeostasis. Paralichthys olivaceus PPARalpha (PoPPARalpha) cDNA was isolated by initial reverse transcription polymerase chain reaction (RT-PCR) using conserved region among fish species and rapid amplification of cDNA ends (RACE). The full-length of PoPPARalpha cDNA is 2040-bp long encoding a polypeptide with 505 amino acids and containing a DNA binding domain (C4-type zinc finger) and a ligand-binding domain. PoPPARalpha was detected from 1 day post-hatch and was highly expressed in the stomach, liver, and intestine of continuously fed flounder, approximately 16 cm in size. PoPPARalpha mRNA expression was down-regulated in the kidney, stomach, and liver of the 4.5-month-old flounder after a 30 day food-deprivation period. PoPPARalpha activates the PPAR response element (PPRE)-driven reporter, and treatment with Wy14643, a PPARalpha agonist, augmented PoPPARalpha-stimulated peroxisome proliferator response element activity in HINAE and HepG2 cells. PoPPARalpha activated the expression of fatty acid beta-oxidation related genes such as carnitine palmitoyltransferase 1A, medium chain acyl-CoA dehydrogenase, and acyl CoA oxidase 1 and inhibited the expression of sterol regulatory element binding protein and fatty acid synthase by competitively inhibiting LXR/RXR heterodimer formation. These results suggest that PoPPARalpha plays an important role in lipid metabolism of olive flounder and that it is functionally and evolutionarily conserved in olive flounder and mammals. PMID- 22051323 TI - The use of methotrexate for treatment of inflammatory bowel disease in clinical practice. AB - BACKGROUND: Methotrexate is considered a treatment for Crohn's disease, whilst few data in ulcerative colitis are available. AIM: To evaluate frequency, indications, efficacy and safety of methotrexate in inflammatory bowel disease patients. METHODS: 5420 case histories were reviewed. RESULTS: Methotrexate was prescribed to 112 patients (2.1%; 89 Crohn's disease, 23 ulcerative colitis). It was the first-line immunosuppressive option in 32 (28.6%), it was an alternative drug due to toxicity or failure of thiopurines in 80 (71.4%). Steroid-dependence represented the main indication both when it was used as first (13/32, 40.6%) and second option (41/80, 51.2%). Efficacy was considered optimal in 39/112 (34.8%), partial in 29/112 (25.9%), absent in 22/112 (19.6%), not assessable in 22/112 (19.6%). Side effects happened in 49 out of 112 patients (43.7%) (39 Crohn's disease, 10 ulcerative colitis), leading to drug discontinuation in 38 (33.9%). The occurrence of side effects was approximately fivefold higher in patients who did not receive folic acid (14/19, 73.7%) than in those who did (35/93, 37.6%): odds ratio 4.64, 95% confidence interval 1.54-14.00; p=0.005. CONCLUSIONS: The use of methotrexate appears to be negligible in clinical practice. However, our results suggest that, if appropriately used, methotrexate could be more widely administered to inflammatory bowel disease patients with complicated disease. PMID- 22051322 TI - Rose hip and its constituent galactolipids confer cartilage protection by modulating cytokine, and chemokine expression. AB - BACKGROUND: Clinical studies have shown that rose hip powder (RHP) alleviates osteoarthritis (OA). This might be due to anti-inflammatory and cartilage protective properties of the complete RHP or specific constituents of RHP. Cellular systems (macrophages, peripheral blood leukocytes and chondrocytes), which respond to inflammatory and OA-inducing stimuli, are used as in vitro surrogates to evaluate the possible pain-relief and disease-modifying effects of RHP. METHODS: (1) Inflammatory processes were induced in RAW264.7 cells or human peripheral blood leukocytes (PBL) with LPS. Inflammatory mediators (nitric oxide (NO), prostaglandin E(2) (PGE(2)) and cytokines/chemokines) were determined by the Griess reaction, EIA and multiplex ELISA, respectively. Gene expression was quantified by RT-PCR. RHP or its constituent galactolipid, GLGPG (galactolipid (2S)-1, 2-di-O-[(9Z, 12Z, 15Z)-octadeca-9, 12, 15-trienoyl]-3-O-beta-D galactopyranosyl glycerol), were added at various concentrations and the effects on biochemical and molecular parameters were evaluated. (2) SW1353 chondrosarcoma cells and primary human knee articular chondrocytes (NHAC-kn) were treated with interleukin (IL)-1beta to induce in vitro processes similar to those occurring during in vivo degradation of cartilage. Biomarkers related to OA (NO, PGE(2), cytokines, chemokines, metalloproteinases) were measured by multiplex ELISA and gene expression analysis in chondrocytes. We investigated the modulation of these events by RHP and GLGPG. RESULTS: In macrophages and PBL, RHP and GLGPG inhibited NO and PGE(2) production and reduced the secretion of cytokines (TNF-alpha, IFN gamma, IL-1beta, IL-6, IL-12) and chemokines (CCL5/RANTES, CXCL10/IP-10). In SW1353 cells and primary chondrocytes, RHP and GLGPG diminished catabolic gene expression and inflammatory protein secretion as shown by lower mRNA levels of matrix metalloproteinases (MMP-1, MMP-3, MMP-13), aggrecanase (ADAMTS-4), macrophage inflammatory protein (MIP-2, MIP-3alpha), CCL5/RANTES, CXCL10/IP-10, IL-8, IL-1alpha and IL-6. The effects of GLGPG were weaker than those of RHP, which presumably contains other chondro-protective substances besides GLGPG. CONCLUSIONS: RHP and GLGPG attenuate inflammatory responses in different cellular systems (macrophages, PBLs and chondrocytes). The effects on cytokine production and MMP expression indicate that RHP and its constituent GLGPG down-regulate catabolic processes associated with osteoarthritis (OA) or rheumatoid arthritis (RA). These data provide a molecular and biochemical basis for cartilage protection provided by RHP. PMID- 22051324 TI - Comment to "rumination syndrome: when the lower oesophageal sphincter rises". PMID- 22051325 TI - Influence of CIT-induced DGF on kidney transplant outcomes. AB - Increased cold ischemia time (CIT) predisposes to delayed graft function (DGF). DGF is considered a risk factor for graft failure after kidney transplantation, but DGF has multiple etiologies. To analyze the risk of CIT-induced DGF on graft survival, we evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one donor resulted in DGF and the other did not, using national Scientific Registry of Transplant Recipients data between 2000 and 2009. Of 54 565 kidney donors, 15 833 were excluded for mate kidney non-transplantation, 27 340 because both or neither kidney developed DGF and 2310 for same/unknown CIT. The remaining 9082 donors (18 164 recipients) were analyzed. The adjusted odds (aOR) of DGF were significantly higher when CIT was longer by >= 1 h (aOR 1.81, 95% CI 1.7-2.0), >= 5 h (aOR 2.5, 95% CI 2.3-2.9), >= 10 h (aOR 3.3, 95% CI 2.7-2.9) and >= 15 h (aOR 4.4, 95% CI 3.4-5.8) compared to shorter CIT transplants. In the multivariable models adjusted for recipient characteristics, graft survival between paired donor transplants, with and without DGF, were similar. These results suggest that DGF, specifically induced by prolonged CIT, has limited bearing on long-term outcomes, which may have important implications for kidney utilization. PMID- 22051326 TI - Acute primary canine herpesvirus-1 dendritic ulcerative keratitis in an adult dog. AB - We present a report of dendritic ulcerative keratitis in a 4-year old locally immunosuppressed dog suspected to result from acute primary canine herpesvirus-1 (CHV-1) infection. The dog was presented for evaluation of mild blepharospasm and conjunctival hyperemia in the right eye (OD) shortly after attending a public boarding facility. For approximately 3 months, the dog had been receiving topical prednisolone acetate 1.0% and tacrolimus 0.02% in both eyes (OU) q12h for treatment of follicular conjunctivitis. Ophthalmic examination revealed three regions of corneal fluorescein retention OD. The lesions had a dendritic pattern, were approximately 2-3 mm in length, and were located at the dorsomedial, lateral, and ventromedial aspects of the cornea. No additional abnormalities were noted on complete ophthalmic and physical examinations. CHV-1 was identified in conjunctival samples OD by polymerase chain reaction, and paired CHV-1 serum virus neutralization antibody titers were positive and consistent with acute infection. Topical prednisolone acetate and tacrolimus were discontinued. The dog was treated with cidofovir 0.5% OU q12h for a period of 4 weeks, with resolution of corneal disease noted within 1 week of treatment. In conjunction with previous studies, this case report supports a central role for alterations in host immune status in the pathogenesis and clinical manifestations of CHV-1 ocular disease in dogs. PMID- 22051327 TI - Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. AB - We reviewed available evidence for cardiovascular effects of n-3 polyunsaturated fatty acid (PUFA) consumption, focusing on long chain (seafood) n-3 PUFA, including their principal dietary sources, effects on physiological risk factors, potential molecular pathways and bioactive metabolites, effects on specific clinical endpoints, and existing dietary guidelines. Major dietary sources include fatty fish and other seafood. n-3 PUFA consumption lowers plasma triglycerides, resting heart rate, and blood pressure and might also improve myocardial filling and efficiency, lower inflammation, and improve vascular function. Experimental studies demonstrate direct anti-arrhythmic effects, which have been challenging to document in humans. n-3 PUFA affect a myriad of molecular pathways, including alteration of physical and chemical properties of cellular membranes, direct interaction with and modulation of membrane channels and proteins, regulation of gene expression via nuclear receptors and transcription factors, changes in eicosanoid profiles, and conversion of n-3 PUFA to bioactive metabolites. In prospective observational studies and adequately powered randomized clinical trials, benefits of n-3 PUFA seem most consistent for coronary heart disease mortality and sudden cardiac death. Potential effects on other cardiovascular outcomes are less-well-established, including conflicting evidence from observational studies and/or randomized trials for effects on nonfatal myocardial infarction, ischemic stroke, atrial fibrillation, recurrent ventricular arrhythmias, and heart failure. Research gaps include the relative importance of different physiological and molecular mechanisms, precise dose responses of physiological and clinical effects, whether fish oil provides all the benefits of fish consumption, and clinical effects of plant-derived n-3 PUFA. Overall, current data provide strong concordant evidence that n-3 PUFA are bioactive compounds that reduce risk of cardiac death. National and international guidelines have converged on consistent recommendations for the general population to consume at least 250 mg/day of long-chain n-3 PUFA or at least 2 servings/week of oily fish. PMID- 22051328 TI - The anti-oxidative capacity of high-density lipoprotein is reduced in acute coronary syndrome but not in stable coronary artery disease. AB - OBJECTIVES: This study examined an anti-inflammatory property of high-density lipoprotein (HDL) in subjects with acute coronary syndrome (ACS) and stable coronary artery disease (CAD) compared with control subjects. BACKGROUND: HDL has anti-inflammatory properties in vitro, but its relationship to coronary disease in humans is unclear. The high-density lipoprotein inflammatory index (HII) measures the ability of HDL to mitigate oxidation of low-density lipoprotein; this function may be impaired in ACS and/or CAD. METHODS: We measured HII in 193 patients undergoing angiography for symptoms of CAD. Control subjects (n = 99) had no angiographic CAD, chronic CAD subjects (n = 51) had >= 70% vessel stenosis, and ACS subjects (n = 43) had >= 20% vessel stenosis and ischemia or infarction. We also examined HII in a cohort of healthy subjects randomly assigned to a statin or placebo. RESULTS: Subjects who had ACS had higher HII (less antioxidative capacity) compared with controls (1.57 vs. 1.17, p = 0.005) or those with chronic CAD (1.57 vs. 1.11, p = 0.006). HII was not different in subjects with stable CAD compared with controls. Furthermore, those subjects with higher HII were more likely to have ACS than no CAD (quartile 4 vs. 1, odds ratio [OR]: 1.74, p = 0.008). In a multivariate logistic regression model, HII was associated with ACS after adjusting for traditional cardiac risk factors (OR: 3.8, p = 0.003). There was a small improvement in HII after statin therapy compared with placebo (-14%, p = 0.03). CONCLUSIONS: HDL has less anti inflammatory capacity as assessed by HII in the setting of ACS compared with controls or subjects with chronic CAD. PMID- 22051329 TI - The association of Framingham and Reynolds risk scores with incidence and progression of coronary artery calcification in MESA (Multi-Ethnic Study of Atherosclerosis). AB - OBJECTIVES: The purpose of this study was to compare the association of the Framingham risk score (FRS) and Reynolds risk score (RRS) with subclinical atherosclerosis, assessed by incidence and progression of coronary artery calcium (CAC). BACKGROUND: The comparative effectiveness of competing risk algorithms for identifying subclinical atherosclerosis is unknown. METHODS: MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 participants free of baseline cardiovascular disease. All participants underwent risk factor assessment, as well as baseline and follow-up CAC testing. We assessed the performance of the FRS and RRS to predict CAC incidence and progression using relative risk and robust linear regression. RESULTS: The study population included 5,140 individuals (mean age 61 +/- 10 years, 47% males, mean follow-up: 3.1 +/- 1.3 years). Among 53% of subjects (n = 2,729) with no baseline CAC, 18% (n = 510) developed incident CAC. Both the FRS and RRS were significantly predictive of incident CAC (relative risk: 1.40 [95% confidence interval (CI): 1.29 to 1.52] and 1.41 [95% CI: 1.30 to 1.54] per 5% increase in risk, respectively) and CAC progression (mean CAC score change: 6.92 [95% CI: 5.31 to 8.54] and 6.82 [95% CI: 5.51 to 8.14] per 5% increase). Discordance in risk category classification (<10% or >10% per 10-year coronary heart disease risk) occurred in 13.7%, with only the RRS consistently adding predictive value for incidence and progression of CAC. These subclinical atherosclerosis findings are supported by a coronary heart disease events analysis over a mean follow-up of 5.6 +/- 0.7 years. CONCLUSIONS: Both the RRS and FRS predict onset and progression of subclinical atherosclerosis. However, the RRS may provide additional predictive information when discordance between the scoring systems exists. PMID- 22051330 TI - The impact of renin-angiotensin-aldosterone system blockade on heart failure outcomes and mortality in patients identified to have aortic regurgitation: a large population cohort study. AB - OBJECTIVES: The aim of this study was to investigate the effect of renin angiotensin system blockade on outcomes in patients with aortic regurgitation (AR). BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have the potential to reduce afterload, blunt left ventricular wall stress, and limit left ventricular dilation and hypertrophy. However, long-term studies have yielded inconsistent results, and very few have assessed clinical outcomes. METHODS: The Health Informatics Centre dispensed prescription and morbidity and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database. Patients diagnosed with at least moderate AR from 1993 to 2008 were identified. Cox regression analysis was used to assess differences in all-cause mortality and cardiovascular (CV) and AR events (heart failure hospitalizations, heart failure deaths, or aortic valve replacement) between those treated with and without ACE inhibitors or angiotensin receptor blockers (ARBs). RESULTS: A total of 2,266 subjects with AR (median age 74 years; interquartile range: 64 to 81 years) were studied, with a mean follow-up period of 4.4 +/- 3.7 years. Seven hundred and five patients (31%) received ACE inhibitor or ARB therapy. There were 582 all-cause deaths (25.7%). Patients treated with ACE inhibitors or ARBs had significantly lower all cause mortality and fewer CV and AR events, with adjusted hazard ratios of 0.56 (95% confidence interval [CI]: 0.64 to 0.89; p < 0.01) for all-cause mortality, 0.77 (95% CI: 0.67 to 0.89; p < 0.01) for CV events, and 0.68 (95% CI: 0.54 to 0.87; p < 0.01) for AR events. CONCLUSIONS: This large retrospective study shows that the prescription of ACE inhibitors or ARBs in patients with moderate to severe AR was associated with significantly reduced all-cause mortality and CV and AR events. These data need to be confirmed by a prospective randomized controlled outcome trial. PMID- 22051331 TI - Renin-angiotensin system blockade and improved clinical outcomes in chronic aortic regurgitation: enough ammunition to revise guidelines, or do we need a randomized controlled trial? PMID- 22051332 TI - Impaired natriuretic and renal endocrine response to acute volume expansion in pre-clinical systolic and diastolic dysfunction. AB - OBJECTIVES: We hypothesized an impaired renal endocrine and natriuretic response to volume expansion (VE) in humans with pre-clinical systolic dysfunction (PSD) and pre-clinical diastolic dysfunction (PDD). We further hypothesized that exogenous B-type natriuretic peptide (BNP) could rescue an impaired natriuretic response in PSD and PDD. BACKGROUND: Recent reports suggest that in early systolic heart failure (HF), there is an impaired natriuretic response to acute VE. METHODS: PSD was defined as left ventricular ejection fraction <40% without HF symptoms. PDD was defined as ejection fraction >50%, moderate to severe diastolic dysfunction by Doppler criteria, and no HF symptoms. A double-blinded, placebo-controlled, crossover study was employed to determine the renal response to VE (0.25 ml/kg/min of normal saline for 60 min) in the presence and absence of exogenous BNP. Twenty healthy control subjects, 20 PSD subjects, and 18 PDD subjects participated. RESULTS: In healthy control subjects, urinary cyclic guanosine monophosphate (cGMP) and natriuresis increased after VE. In contrast, among PSD and PDD subjects, there was a paradoxical decrease in urinary cGMP and attenuated natriuresis. Pre-treatment with subcutaneous BNP resulted in similar increases in both urinary cGMP and natriuresis among healthy normal, PSD, and PDD subjects. CONCLUSIONS: In PSD and PDD, there is impaired renal cGMP activation, which contributes to impaired natriuresis in response to VE. Impaired activation of urinary cGMP and reduced natriuresis may contribute to volume overload and the progression of HF among PSD and PDD subjects. Importantly, the impaired renal excretory response to VE is rescued by exogenous BNP in PSD and PDD. PMID- 22051333 TI - The early intertwining of the heart and the kidney through an impaired natriuretic response to acute volume expansion. PMID- 22051334 TI - Mechanical stretch of atrial myocyte monolayer decreases sarcoplasmic reticulum calcium adenosine triphosphatase expression and increases susceptibility to repolarization alternans. AB - OBJECTIVES: The purpose of this study was to investigate the effect of stretch (the major risk factor for atrial fibrillation [AF]) on spatial and temporal alternations of action potential duration (APD-ALT) and calcium transient in cultured atrial myocyte monolayer. BACKGROUND: How rapid firings or premature beats trigger AF is not completely understood. Discordant repolarization alternans, characterized by simultaneous prolongation and shortening of APD in different myocardial regions, is central to the genesis of ventricular fibrillation. We hypothesized that repolarization alternans also is central to the initiation of multiple re-entry circuits and AF. METHODS: Confluent HL-1 atrial myocyte monolayer with spontaneous depolarization was cultured in silicone membrane and subjected to mechanical stretch. Rapid field pacing was used to induce alternans. A high-resolution dual optical mapping system was used to record action potentials and calcium transients. RESULTS: High-rate pacing induced APD-ALT and calcium transient in atrial myocyte monolayer. Mechanical stretch significantly decreased the thresholds for APD-ALT and calcium transient. Mechanical stretch decreased the expression of sarcoplasmic reticulum adenosine triphosphatase 2, and thus slower calcium reuptake kinetics, which was responsible for the susceptibility to alternans. Mechanical stretch did not alter the APD restitution kinetics. Mechanical stretch also enhanced spatially discordant alternans. Overexpression of sarcoplasmic reticulum adenosine triphosphatase 2 reversed all the effects of stretch on susceptibility to alternans. In intact atrium, mechanical stretch also enhanced discordant alternans. CONCLUSIONS: Mechanical stretch increased the susceptibility to alternans in atrial myocytes, which may explain the susceptibility to AF in conditions of atrial stretch, such as mitral valvular heart disease, heart failure, and hypertension. PMID- 22051335 TI - Repolarization alternans in dilated pulsing atria: a preventable "prelude" to atrial fibrillation? PMID- 22051336 TI - Reduced collagen deposition in infarcted myocardium facilitates induced pluripotent stem cell engraftment and angiomyogenesis for improvement of left ventricular function. AB - OBJECTIVES: The purpose of this study was to assess the effect of scar tissue composition on engraftment of progenitor cells into infarcted myocardium. BACKGROUND: Scar tissue formation after myocardial infarction creates a barrier that severely compromises tissue regeneration, limiting potential functional recovery. METHODS: In vitro: A tricell patch (Tri-P) was created from peritoneum seeded and cultured with induced pluripotent stem cell-derived cardiomyocytes, endothelial cells, and mouse embryonic fibroblasts. The expression of fibrosis related molecules from mouse embryonic fibroblasts and infarcted heart was measured by Western blot and quantitative reverse transcriptase polymerase chain reaction. In vivo: A Tri-P was affixed over the entire infarcted area 7 days after myocardial infarction in mice overexpressing adenylyl cyclase 6 (AC6). Engraftment efficiency of progenitor cells in hearts of AC6 mice was compared with that of control wild-type (WT) mice using a combination of in vivo bioluminescence imaging, post-mortem ex vivo tissue analysis, and the number of green fluorescent protein-positive cells. Echocardiography of left ventricular (LV) function was performed weekly. Hearts were harvested for analysis 4 weeks after Tri-P application. Mouse embryonic fibroblasts were stimulated with forskolin before an anoxia/reoxygenation protocol. Fibrosis-related molecules were analyzed. RESULTS: In AC6 mice, infarcted hearts treated with Tri-P showed significantly higher bioluminescence imaging intensity and numbers of green fluorescent protein-positive cells than in WT mice. LV function improved progressively in AC6 mice from weeks 2 to 4 and was associated with reduced LV fibrosis. CONCLUSIONS: Application of a Tri-P in AC6 mice resulted in significantly higher induced pluripotent stem cell engraftment accompanied by angiomyogenesis in the infarcted area and improvement in LV function. PMID- 22051337 TI - A tale of 2 biologies: stem cell patch: myocardial interactions are critical for myocardial regeneration. PMID- 22051338 TI - Persistent left superior vena cava with retrograde drainage from the left atrium into the left brachiocephalic vein. PMID- 22051339 TI - A rare combination of two rare diseases: left ventricular noncompaction and hypertrophic cardiomyopathy. PMID- 22051340 TI - Diabetogenic T lymphocytes in human Type 1 diabetes. AB - The field of Type 1 diabetes research has been quick to embrace the era of translational medicine in the recent epoch. Building upon some 30 years of intense immunological research, the past decade has been marked by a series of clinical trials designed to evaluate the potential beneficial effects of a range of immune intervention and prevention strategies [1(**),2-5]. At the heart of Type 1 diabetes is an autoimmune process, the consequence of which is immune mediated destruction of islet beta-cells. Although understanding the pathogenesis of islet autoimmunity is critical, there are also good reasons to focus research onto the beta-cell destructive process itself. Measuring preservation of function of insulin-producing cells is currently the best means available to evaluate potential beneficial effects of immunotherapy, but there is an urgent need to discover and monitor immunological correlates of this beta-cell destructive process. Whilst the best approach to intervention and prevention has yet to emerge, it is logical that future attempts to intelligently design therapeutics for Type 1 diabetes will need to be predicated on a clear understanding of the process of beta-cell destruction and the immune components involved. For these reasons, this review will focus on the role of diabetogenic T lymphocytes in this disease-defining event. PMID- 22051341 TI - Evaluation of the seasonal performance of a water reclamation pond-constructed wetland system for removing emerging contaminants. AB - The capacity of a full-scale reclamation pond-constructed wetland (CW) system to eliminate 27 emerging contaminants (i.e. pharmaceuticals, sunscreen compounds, fragrances, antiseptics, fire retardants, pesticides, and plasticizers) and the seasonal occurrence of these contaminants is studied. The compounds with the highest concentrations in the secondary effluent are diclofenac, caffeine, ketoprofen, and carbamazepine. The results show that the constructed wetland (61%) removes emerging contaminants significantly more efficiently than the pond (51%), presumably due to the presence of plants (Phragmites and Thypa) as well as the higher hydraulic residence time (HRT) in the CW. A greater seasonal trend to the efficient removal of these compounds is observed in the pond than in the CW. The overall mass removal efficiency of each individual compound ranged from 27% to 93% (71% on average), which is comparable to reported data in advanced treatments (photo-fenton and membrane filtration). The seasonal average content of emerging contaminants in the river water (2488 ng L(-1)) next to the water reclamation plant is found to be higher than the content in the final reclaimed water (1490 ng L(-1)), suggesting that the chemical quality of the reclaimed water is better than available surface waters. PMID- 22051342 TI - Sunlight-induced degradation of soil-adsorbed veterinary antimicrobials Marbofloxacin and Enrofloxacin. AB - Marbofloxacin (MAR) and Enrofloxacin (ENR), two largely employed veterinary Fluoroquinolones (FQs), were found to be present at the micrograms per kilogram level in agricultural soils of South Lombardy (Italy) several months after manuring. Distribution coefficients (K(d)) from sorption experiments indicated a strong binding to the soil. Soil samples fortified with environmentally significant FQs amounts (0.5 mg kg(-1)) were exposed to solar light that promoted extensive degradation (80%) of both drugs in 60-150 h. Thus, photochemistry could be considered a significant depollution path in the soil, although it was two orders of magnitudes slower than in aqueous solution and a fraction of the drug (ca. 20%) remained unaffected. For MAR the photoprocess was the same as in solution, and involved cleavage of the tetrahydrooxadiazine ring. On the contrary, with ENR only some of the photoproducts determined in water (those arising from a stepwise oxidation of the piperazine side chain) were observed. Substitution of the 6-fluoro by a hydroxyl group and reduction did not occur in the soil, supporting the previous contention that such processes required polar solvation of FQs. Consistently with this rationalization, the irradiation of thin layers of solid drugs led to essentially the same products distribution as in the soil. From the environmental point of view it is important to notice that photodegradation mainly affects the side-chains, while the fluoroquinolone ring, to which the biological effect is associated, is conserved up to the later stages of the degradation. PMID- 22051343 TI - Antibiotic resistant bacteria/genes dissemination in lacustrine sediments highly increased following cultural eutrophication of Lake Geneva (Switzerland). AB - This study investigates faecal indicator bacteria (FIB), multiple antibiotic resistant (MAR), and antibiotic resistance genes (ARGs), of sediment profiles from different parts of Lake Geneva (Switzerland) over the last decades. MARs consist to expose culturable Escherichia coli (EC) and Enterococcus (ENT) to mixed five antibiotics including Ampicillin, Tetracycline, Amoxicillin, Chloramphenicol and Erythromycin. Culture-independent is performed to assess the distribution of ARGs responsible for, beta-lactams (blaTEM; Amoxicillin/Ampicillin), Streptomycin/Spectinomycin (aadA), Tetracycline (tet) Chloramphenicol (cmlA) and Vancomycin (van). Bacterial cultures reveal that in the sediments deposited following eutrophication of Lake Geneva in the 1970s, the percentage of MARs to five antibiotics varied from 0.12% to 4.6% and 0.016% to 11.6% of total culturable EC and ENT, respectively. In these organic-rich bacteria-contaminated sediments, the blaTEM resistant of FIB varied from 22% to 48% and 16% to 37% for EC and ENT respectively, whereas the positive PCR assays responsible for tested ARGs were observed for EC, ENT, and total DNA from all samples. The aadA resistance gene was amplified for all the sediment samples, including those not influenced by WWTP effluent water. Our results demonstrate that bacteria MARs and ARGs highly increased in the sediments contaminated with WWTP effluent following the cultural eutrophication of Lake Geneva. Hence, the human-induced changing limnological conditions highly enhanced the sediment microbial activity, and therein the spreading of antibiotic resistant bacteria and genes in this aquatic environment used to supply drinking water in a highly populated area. Furthermore, the presence of the antibiotic resistance gene aadA in all the studied samples points out a regional dissemination of this emerging contaminant in freshwater sediments since at least the late nineteenth century. PMID- 22051344 TI - Assessment of exposure to PCB 153 from breast feeding and normal food intake in individual children using a system approach model. AB - Investigators have typically relied on a single or few discrete time points as measures of polychlorinated biphenyl (PCB) body burden, however health effects are more likely to be the result of integrative exposure in time, optionally expressed as an area under the time curve (AUC) of PCB serum concentration. Using data from a subgroup of 93 infants from a birth cohort in eastern Slovakia-a region highly polluted by PCBs-we fit a system type model, customized to our longitudinal measures of serum PCB concentrations in cord, 6, 16, and 45 month blood specimens. The most abundant congener, PCB 153, was chosen for modeling purposes. In addition to currently used methods of exposure assessment, our approach estimates a concentration time profile for each subject, taking into account mean residence time of PCB 153 molecules in the body, duration of breast feeding, hypothetical PCB 153 concentration in steady-state without breast feeding and alternately without normal food intake. Hypothetical PCB 153 concentration in steady-state without normal food intake correlates with AUC (r=0.84, p<0.001) as well as with duration of breast feeding (r=0.64, p<0.001). It makes possible to determine each subject's exposure profile expressed as AUC of PCBs serum concentration with a minimum model parameters. PCB body burden in most infants was strongly associated with duration of breast feeding in most, but not all children, was apparent from model output. PMID- 22051345 TI - Influence of dissolved humic substances on the mass transfer of organic compounds across the air-water interface. AB - The effect of dissolved humic substances (DHS) on the rate of water-gas exchange of two volatile organic compounds was studied under various conditions of agitation intensity, solution pH and ionic strength. Mass-transfer coefficients were determined from the rate of depletion of model compounds from an apparatus containing a stirred aqueous solution with continuous purging of the headspace above the solution (dynamic system). Under these conditions, the overall transfer rate is controlled by the mass-transfer resistance on the water side of the water gas interface. The experimental results show that the presence of DHS hinders the transport of the organic molecules from the water into the gas phase under all investigated conditions. Mass-transfer coefficients were significantly reduced even by low, environmentally relevant concentrations of DHS. The retardation effect increased with increasing DHS concentration. The magnitude of the retardation effect on water-gas exchange was compared for Suwannee River fulvic and humic acids, a commercially available leonardite humic acid and two synthetic surfactants. The observed results are in accordance with the concept of hydrodynamic effects. Surface pressure forces due to surface film formation change the hydrodynamic characteristics of water motion at the water-air interface and thus impede surface renewal. PMID- 22051346 TI - Polycyclic aromatic hydrocarbons: bees, honey and pollen as sentinels for environmental chemical contaminants. AB - Three beehive matrices, sampled in six different apiaries from West France, were analyzed for the presence of four polycyclic aromatic hydrocarbons (PAH4: benzo[a]pyrene, benzo[a]anthracene, benzo[b]fluoranthene and chrysene). Samples were collected during four different periods in both 2008 and 2009. Honey samples showed the lowest levels of PAH4 contamination (min=0.03 MUg kg(-1); max=5.80 MUg kg(-1); mean=0.82 MUg kg(-1); Sd=1.17). Bee samples exhibited higher levels of PAH4 contamination (min=0.32 MUg kg(-1); max=73.83 MUg kg(-1); mean=7.03 MUg kg( 1); Sd=17.83) with a great dispersion of the concentrations due to four main events of high concentrations. Pollen samples showed only one major episode with the highest PAH4 concentration found (min=0.33 MUg kg(-1); max=129.41 MUg kg(-1); mean=7.10 MUg kg(-1); Sd=22.28). The PAH4 concentrations found were significantly influenced by the landscape context for all beehive samples. PMID- 22051347 TI - Increasing levels of long-chain perfluorocarboxylic acids (PFCAs) in Arctic and North Atlantic marine mammals, 1984-2009. AB - Temporal variations in concentrations of perfluorinated carboxylic acids (PFCAs) and sulfonic acids (PFSAs), including perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) structural isomers, were examined in livers of pilot whale (Globicephala melas), ringed seal (Phoca hisida), minke whale (Balaenoptera acutorostrata), harbor porpoise (Phocoena phocoena), hooded seal (Cystophora cristata), Atlantic white-sided dolphin (Lagenorhynchus acutus) and in muscle tissue of fin whales (Balaenoptera physalus). The sampling spanned over 20 years (1984-2009) and covered a large geographical area of the North Atlantic and West Greenland. Liver and muscle samples were homogenized, extracted with acetonitrile, cleaned up using hexane and solid phase extraction (SPE), and analyzed by liquid chromatography with negative electrospray tandem mass spectrometry (LC-MS/MS). In general, the levels of the long-chained PFCAs (C9 C12) increased whereas the levels of PFOS remained steady over the studied period. The PFOS isomer pattern in pilot whale liver was relatively constant over the sampling years. However, in ringed seals there seemed to be a decrease in linear PFOS (L-PFOS) with time, going from 91% in 1984 to 83% in 2006. PMID- 22051348 TI - Genetic co-morbidity between neuroticism, anxiety/depression and somatic distress in a population sample of adolescent and young adult twins. AB - BACKGROUND: Genetic studies in adults indicate that genes influencing the personality trait of neuroticism account for substantial genetic variance in anxiety and depression and in somatic health. Here, we examine for the first time the factors underlying the relationship between neuroticism and anxiety/depressive and somatic symptoms during adolescence. METHOD: The Somatic and Psychological Health Report (SPHERE) assessed symptoms of anxiety/depression (PSYCH-14) and somatic distress (SOMA-10) in 2459 adolescent and young adult twins [1168 complete pairs (35.4% monozygotic, 53% female)] aged 12-25 years (mean=15.5 +/- 2.9). Differences between boys and girls across adolescence were explored for neuroticism, SPHERE-34, and the subscales PSYCH-14 and SOMA-10. Trivariate analyses partitioned sources of covariance in neuroticism, PSYCH-14 and SOMA-10. RESULTS: Girls scored higher than boys on both neuroticism and SPHERE, with SPHERE scores for girls increasing slightly over time, whereas scores for boys decreased or were unchanged. Neuroticism and SPHERE scores were strongly influenced by genetic factors [heritability (h(2)) = 40-52%]. A common genetic source influenced neuroticism, PSYCH-14 and SOMA-10 (impacting PSYCH-14 more than SOMA-10). A further genetic source, independent of neuroticism, accounted for covariation specific to PSYCH-14 and SOMA-10. Environmental influences were largely specific to each measure. CONCLUSIONS: In adolescence, genetic risk factors indexed by neuroticism contribute substantially to anxiety/depression and, to a lesser extent, perceived somatic health. Additional genetic covariation between anxiety/depressive and somatic symptoms, independent of neuroticism, had greatest influence on somatic distress, where it was equal in influence to the factor shared with neuroticism. PMID- 22051350 TI - Towards a species level tree of the globally diverse genus Chenopodium (Chenopodiaceae). AB - Chenopodium is a large and morphologically variable genus of annual and perennial herbs with an almost global distribution. All subgenera and most sections of Chenopodium were sampled along with other genera of Chenopodieae, Atripliceae and Axyrideae across the subfamily Chenopodioideae (Chenopodiaceae), totalling to 140 taxa. Using Maximum parsimony and Bayesian analyses of the non-coding trnL-F (cpDNA) and nuclear ITS regions, we provide a comprehensive picture of relationships of Chenopodium sensu lato. The genus as broadly classified is highly paraphyletic within Chenopodioideae, consisting of five major clades. Compared to previous studies, the tribe Dysphanieae with three genera Dysphania, Teloxys and Suckleya (comprising the aromatic species of Chenopodium s.l.) is now shown to form one of the early branches in the tree of Chenopodioideae. We further recognize the tribe Spinacieae to include Spinacia, several species of Chenopodium, and the genera Monolepis and Scleroblitum. The Chenopodium rubrum and the Ch. murale-clades were newly discovered as distinct major lineages but their relationships within Chenopodioideae will need further evaluation. Based on our results, we suggest the delimitation of Chenopodium to include Einadia and Rhagodia because these are part of the crown group composed of species of subg. Chenopodium that appear sister to the Atripliceae. The tetraploid crops such as Ch. berlandieri subsp. nuttalliae and Ch. quinoa also belong to Chenopodium sensu stricto. Trees derived from trnL-F and ITS were incongruent within this shallow crown group clade. Possible biological causes are discussed, including allopolyploidization. PMID- 22051349 TI - A new role for laminins as modulators of protein toxicity in Caenorhabditis elegans. AB - Protein misfolding is a common theme in aging and several age-related diseases such as Alzheimer's and Parkinson's disease. The processes involved in the development of these diseases are many and complex. Here, we show that components of the basement membrane (BM), particularly laminin, affect protein integrity of the muscle cells they support. We knocked down gene expression of epi-1, a laminin alpha-chain, and found that this resulted in increased proteotoxicity in different Caenorhabditis elegans transgenic models, expressing aggregating proteins in the body wall muscle. The effect could partially be rescued by decreased insulin-like signaling, known to slow the aging process and the onset of various age-related diseases. Our data points to an underlying molecular mechanism involving proteasomal degradation and HSP-16 chaperone activity. Furthermore, epi-1-depleted animals had altered synaptic function and displayed hypersensitivity to both levamisole and aldicarb, an acetylcholine receptor agonist and an acetylcholinesterase inhibitor, respectively. Our results implicate the BM as an extracellular modulator of protein homeostasis in the adjacent muscle cells. This is in agreement with previous research showing that imbalance in neuromuscular signaling disturbs protein homeostasis in the postsynaptic cell. In our study, proteotoxicity may indeed be mediated by the neuromuscular junction which is part of the BM, where laminins are present in high concentration, ensuring the proper microenvironment for neuromuscular signaling. Laminins are evolutionarily conserved, and thus the BM may play a much more causal role in protein misfolding diseases than currently recognized. PMID- 22051351 TI - Evaluation of patient's understanding and recall of the consent process after open inguinal hernia repairs. AB - INTRODUCTION: Open inguinal Hernia repair is one of the most commonly performed operative procedure. Despite this, hernia repair can cause considerable morbidity and rarely mortality. Some of these complications such as chronic pain and testicular complications can be easily disregarded, thereby leading to medico legal claims being made. As a result, the quality of consent process is crucial in increasing patient satisfaction after inguinal hernia repair. This is a prospective study exploring patient's recall of the consenting practice after elective open inguinal hernia repairs at our institute. METHODS: Patients who had an elective, Lichtenstein inguinal hernia repair between January to October 2009 were identified. Patients were contacted by telephone after 3 days and a questionnaire was completed. RESULTS: There were 86 patients included in our study. The male:female ratio was 70:16 whilst the average age was 63.2+/-19.2 years. 42 patients stated pain relief as the main indication for having the operation whilst 30 patients feared incarceration or strangulation as the main indication. Infection was the complication recalled most by patients in our study (31 patients), followed by bleeding (30 patients). Only 2 patients were aware of developing potential chronic pain and 10 patients realised the potential for testicular problems. 57 patients were aware of having a mesh inside their groin. There were 61 patients who were aware of laparoscopic approach as an alternative to open inguinal hernia repair. CONCLUSIONS: Recall of consent is very poor. As a result, repeating the information stated and providing additional resource may reinforce the consent process. PMID- 22051352 TI - Stroke incidence and usage rate of thrombolysis in a Japanese urban city: the Kurashiki stroke registry. AB - BACKGROUND: To investigate stroke incidence and rate of thrombolytic therapy in an urban city of around 500,000 residents. METHODS: Patients suffering acute stroke in Kurashiki City (population 474,415) between March 2009 and February 2010 (inclusive) and admitted to 1 of 10 hospitals throughout the city were prospectively enrolled. RESULTS: We enrolled patients with first-ever stroke (n = 763; men 415; median age 72 years) and first-ever/recurrent stroke (n = 1009; men 552; median age 73 years). Among first-ever strokes, 68% were cerebral infarctions, 23% were intracerebral hemorrhages, and 8% were subarachnoid hemorrhages. Crude incidences for first-ever stroke per 100,000 residents were 159.8 (95% confidence interval [CI] 148.4-171.1) for all strokes, 108.8 (95% CI 99.4-118.1) for cerebral infarction, and 36.5 (95% CI 31.0-41.9) for intracerebral hemorrhage. After adjustment using the world population model, age adjusted incidences were 60.7 (95% CI 45.4-75.9) for all strokes, 38.4 (95% CI 26.3-50.5) for cerebral infarction, and 16.1 (95% CI 8.3-24.0) for intracerebral hemorrhage. Among 698 cases with first-ever and recurrent cerebral infarction, thrombolysis was administered for 31 (5%). Of 197 cerebral infarction patients admitted within 3 hours of onset, the thrombolysis rate was 16%. CONCLUSION: In this urban Japanese city, the age-adjusted incidence of first-ever stroke between March 2009 and February 2010 was 60.7 per 100,000 residents, which was relatively low compared with findings for other countries. Thrombolysis was given to approximately 5% of patients with acute ischemic stroke. PMID- 22051353 TI - Psychological well-being and the body dissatisfaction-bulimic symptomatology relationship: an examination of moderators. AB - Research has examined psychological moderators of the body dissatisfaction bulimic symptomatology relationship, but the focus has been on variables thought to worsen the relationship. In this study, we examined self-esteem, optimism, satisfaction with life, and self-determination as potential buffers. Participants were 847 female undergraduates. Using hierarchical multiple regression (HMR), we controlled for the influences of social desirability and body mass index on bulimic symptomomatology and then determined the main and interactive effects of body dissatisfaction and each moderator. Self-determination, optimism, self esteem, and satisfaction with life all buffered the deleterious effects of body dissatisfaction, such that when levels of the moderators were high, the relationship between body dissatisfaction and bulimic symptomatology was weakest. Knowing what psychological variables moderate women's body dissatisfaction can assist psychologists and other health professionals in developing effective treatments for lessening disordered eating among women. PMID- 22051354 TI - Typology of emergent eating patterns in early childhood. AB - The stability of eating patterns from infancy through childhood is largely unknown. This study identified subgroups of children based on emergent eating patterns from ages 1 to 3 years and examined differences between groups in demographic, anthropometric and temperamental variables. We conducted secondary analyses of 262 boys and 225 girls from the Colorado Adoption Project. Three eating styles (Reactivity to Food, Predictable Appetite, Distractibility at Mealtime) and five temperaments were assessed at ages 1 and 3 years. Weight and height (length) were assessed on children and mothers. Correlations examined the stability of eating patterns, cluster analysis identified subgroups of emergent eating styles, and analysis of variance identified variables differentiating the derived subgroups. Eating styles were moderately stable over time, although all increased on average. Four subgroups were identified: Diet Expanding and Preference Establishing Eaters (37%), Emerging Reactive Tendency Eaters (23%), Emerging Food-Indifferent and Non-Fussy Eaters (31%), and Emerging High-Reactive and Fussy Eaters (9%). The subgroups differed in year 1 Wt/L and Reaction to Food, and year 1-to-3 changes in Emotionality and Reaction to Food. Four emergent eating patterns were identified. How these subgroups of children differ in later weight and health trajectories warrants research. PMID- 22051355 TI - Making implicit measures of associations with snack foods more negative through evaluative conditioning. AB - The present study examined whether implicit measures of associations with snack foods and food consumer behaviour could be changed through a picture-picture evaluative conditioning procedure. In the experimental condition (n=41), female participants completed a conditioning procedure in which pictures of snack foods were paired with images of negatively valenced female body shapes, and pictures of fruits were paired with images of positively valenced body shapes. In a control condition (n=44), snack and fruit stimuli were randomly paired with positively and negatively valenced body shapes. Implicit measures of associations with high-fat snack foods were obtained by using a positive and a negative unipolar single category Implicit Association Test (sc-IAT). A virtual supermarket task was used to assess food consumer behaviour. Results indicated that participants in the experimental condition held a less positive association with high-fat foods on the positive sc-IAT and a more negative association with these foods on the negative sc-IAT as compared to control participants. Opposed to our hypothesis, no behavioural differences were found between the groups. These results imply that this form of associative learning can produce shifts in implicit measures of food evaluations, though behavioural effects were absent. PMID- 22051356 TI - Evaluation of the French version of the Orientation Towards Chocolate Questionnaire: chocolate-related guilt and ambivalence are associated with overweight and disordered eating. AB - The aims of this study were firstly to evaluate the psychometric properties of the French version of the Orientation towards Chocolate Questionnaire (OCQ), secondly to examine differences in chocolate craving as a function of weight status, and thirdly to examine the OCQ craving dimensions as predictors of body dissatisfaction and disordered eating. Participants included 247 female students from the University of Toulouse, France, who completed measures of chocolate craving, body dissatisfaction, bulimia, drive for thinness, and emotional eating, and for whom body mass index (BMI) was available. Confirmatory factor analysis supported the three-factor model of the OCQ, with guilt, approach, and avoidance subscales. Patterns of endorsement of chocolate craving dimensions differed according to weight status, with ambivalence present only amongst overweight participants. Guilt and approach were positively associated with disordered eating, whereas avoidance was negatively associated with bulimia. These results confirm the validity and reliability of the French version of the OCQ and highlight strong associations between chocolate craving dimensions and disordered eating patterns. PMID- 22051357 TI - The 'freshman 15': trends and predictors in a sample of multiethnic men and women. AB - This study focused on predictors of the 'freshman 15' phenomenon among university students. Participants (N=390) included men and women who identified as African American (32%), Latino American (27%), and European American (41%). Students gained on average 3.2 lbs and 0.5 in BMI from their first through third semesters. Changes in weight and BMI did not differ by gender or racial/ethnic group. Students with lower Scholastic Aptitude Test (SAT) scores were more likely to experience the 'freshman 15'. Results suggest that universities should work with students who may be underprepared for college in order to minimize weight gain. PMID- 22051358 TI - The EDE-Q, BULIT-R, and BEDT as self-report measures of binge eating disorder. AB - Binge eating disorder, currently classified as an eating disorder not otherwise specified, is a valid and clinically useful psychiatric diagnosis. Given its probable inclusion in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V), identification of self-report measures with high levels of diagnostic utility should improve the likelihood and accuracy of screening. The aim of the current study was to assess the diagnostic utility of two widely used measures of eating disorder symptoms, namely the Eating Disorder Examination-Questionnaire (EDEQ) and the Bulimia Test-Revised (BULIT-R), as well as a factor of the BULIT-R (coined the Binge Eating Disorder Test or BEDT), newly created specifically for the assessment of BED. Participants included 15 individuals with BED and 26 non-BED controls, as determined via the diagnostic section of the Eating Disorder Examination, who met criteria for being overweight or obese. Results showed that the BEDT achieved 100% sensitivity, specificity, positive and negative predictive values. The BULIT-R and Eating Concern subscale of the EDE-Q evidenced strong sensitivity (100 vs 87), specificity (96 vs 100), positive predictive values (94 vs 100), and negative predictive values (100 vs 93), respectively. Results suggest that the BEDT is an excellent overall measure of BED in obese populations. The BULIT-R affords the advantage of ruling out compensatory behaviors, particularly of the non-purging variety (e.g., severe restriction outside of binges), while the brevity of the Eating Concern subscale of the EDE-Q makes it optimal for use in brief screening situations. PMID- 22051359 TI - Food thought suppression: a matched comparison of obese individuals with and without binge eating disorder. AB - Preliminary studies of non-clinical samples suggest that purposely attempting to avoid thoughts of food, referred to as food thought suppression, is related to a number of unwanted eating- and weight-related consequences, particularly in obese individuals. Despite possible implications for the treatment of obesity and eating disorders, little research has examined food thought suppression in obese individuals with binge eating disorder (BED). This study compared food thought suppression in 60 obese patients with BED to an age-, gender-, and body mass index (BMI)-matched group of 59 obese persons who do not binge eat (NBO). In addition, this study examined the associations between food thought suppression and eating disorder psychopathology within the BED and NBO groups and separately by gender. Participants with BED and women endorsed the highest levels of food thought suppression. Food thought suppression was significantly and positively associated with many features of ED psychopathology in NBO women and with eating concerns in men with BED. Among women with BED, higher levels of food thought suppression were associated with higher frequency of binge eating, whereas among men with BED, higher levels of food thought suppression were associated with lower frequency of binge eating. Our findings suggest gender differences in the potential significance of food thought suppression in obese groups with and without co-existing binge eating problems. PMID- 22051360 TI - Measuring the meanings of eating in minority youth. AB - The aim of this study is to present the development of the Meanings of Eating Index (MEI) in a diverse sample of children. Exploratory factor analysis was performed on MEI items. Factors with eigenvalues above 1.0 were retained. Items that loaded on multiple factors or with item-total correlations below 0.50 were discarded. A 24-item, 5-factor scale comprised the final MEI. Personal Negative Emotions and Disturbed Eating were positively associated with frequency of high calorie snack food intake (r=0.21, p<0.05; r=0.33, p<0.01), and Personal Well Being was positively associated with eating vegetables more frequently (r=0.20; p<0.05). Eating on Behalf of Others was negatively associated with frequency of vegetable intake (r=-.20; p<0.05). Pleasure Eating was not associated with dietary intake. The MEI shows promise as a tool for understanding the affective determinants of dietary intake in minority youth. PMID- 22051361 TI - Binge Eating Disorder and body image perception among university students. AB - Binge Eating Disorder (BED) is characterized by recurrent episodes of compulsive eating, without any compensatory behavior to avoid possible gain weight. Individuals who suffer from eating disorders often show negative self-image. The present paper aimed to assess BED prevalence and self-image disorders among university students in the city of Sao Jose do Rio Preto, State of Sao Paulo, Brazil. The survey had the participation of 217 undergraduates. The following procedures were carried out: a personal data questionnaire, the Binge Eating Scale and a figure scale. In the surveyed population, 12.90% showed BED. Most subjects (86.32%) chose larger figures when compared to their current BMI, overestimating their body size. Furthermore, BED individuals showed higher self image inadequacy in comparison to people without the disorder. Therefore, this is a public health problem to which undergraduates are exposed; forthcoming studies may be carried out to understand BED and associated commorbidities. PMID- 22051362 TI - Loss of control over eating in pre-adolescent youth: the role of attachment and self-esteem. AB - OBJECTIVE: The present study aimed to add to the limited literature on the role of self-esteem and attachment for the explanation of loss of control over eating (LC) among pre-adolescent boys and girls. METHOD: Self-report questionnaires were administered to a community sample of 555 children (8-11 years; 47% female). RESULTS: Children reporting LC (17.6% of the sample) were characterized by a lower self-esteem and less secure attachment toward both of their parents. No gender differences emerged. Moreover, the relation between self-esteem and LC was fully mediated by attachment toward mother and partially mediated by attachment toward father. DISCUSSION: The present study provides preliminary evidence for the idea that the influence of self-esteem on LC seems to operate through a third variable that is an insecure relationship with the parents. Longitudinal research is needed to further elucidate the influence of interpersonal factors on the development of LC. PMID- 22051364 TI - Objectified body consciousness in relation to recovery from an eating disorder. AB - In Western society, the feminine body has been positioned as an object to be looked at and sexually gazed upon; thus, females often learn to view themselves as objects to be observed (i.e., objectified body consciousness (OBC)). This study examined the relation between OBC and eating disorder recovery by comparing its components across non-eating disorder controls, fully recovered, partially recovered, and active eating disorder cases. Results revealed that non-eating disorder controls and fully recovered individuals had similarly low levels of two components of OBC, body surveillance and body shame. Partially recovered individuals looked more similar to those with an active eating disorder on these constructs. The third component of OBC, control beliefs, and a conceptually similar construct, weight/shape self-efficacy, did not differ across groups. Results provide support for the importance of measuring aspects of self objectification, particularly body surveillance and body shame, across the course of an eating disorder. PMID- 22051363 TI - Multiple health behaviors: patterns and correlates of diet and exercise in a Hispanic college sample. AB - Obesity rates are alarming in various ethnocultural groups, particularly in Hispanics. With Hispanics being the fastest growing group to enter college, the aims of the current study were to examine patterns and correlates of exercise and dietary behaviors in Hispanic college students. Data were collected from 693 Hispanic undergraduates who enrolled online and received course extra credit for participation. Individuals completed questionnaires assessing constructs of the transtheoretical model for three health behaviors (exercise, dietary fat, and fruit/vegetable stages of change) along with demographic, psychosocial, and acculturation measures. Less than 1% of students had 0 obesity-relevant risks, while 68% indicated 2 or more risks. Only 2% of the sample met fruit and vegetable guidelines. Lower income was associated with greater obesity-relevant risks, while stress coping ability was associated with fewer such risks. Findings indicate specific obesity risk behaviors in Hispanic college students and suggest demographic and psychosocial targets for prevention and intervention according to stage of change. PMID- 22051365 TI - Interactive effects of dietary restraint and adiposity on stress-induced eating and the food choice of children. AB - The Individual Differences Model posits that individual differences in physiological and psychological factors explain eating behaviors in response to stress. The purpose was to determine the effects of individual differences in adiposity, dietary restraint and stress reactivity on children's energy intake and food choices. A total of 40 boys and girls, age 8-12 years, with wide ranges of dietary restraint, adiposity, and stress reactivity were measured for total energy intake and choice of energy dense 'comfort' and lower density 'healthy' foods following reading and speech stressor manipulations. When exploring the interaction of dietary restraint and stress reactivity, lower restraint/lower reactivity and lower restraint/higher reactivity were associated with reductions in energy intake (37-62 kcal) and comfort food (33-89 kcal). Higher restraint/lower reactivity was associated with consuming 86 fewer total kcal and 45 fewer kcal of comfort food. Only higher restraint/higher reactivity predicted increased energy intake (104 kcal) and comfort food (131 kcal). The interaction of dietary restraint and percentage body fat revealed that lower restraint/lower adiposity was associated with consuming 123 fewer kcal after being stressed with the entire reduction due to a decrease in comfort food. Lower restraint/higher adiposity was associated with consuming 116 kcal more after being stressed with 70% (81 kcal) of the increase in the form of comfort foods. Higher restraint/lower adiposity and higher restraint/higher adiposity were associated with smaller changes in total energy intake of 22 kcal and 1 kcal; respectively. Both restraint and adiposity moderated the effect of stress on energy intake and food choice. Children with greater adiposity may be at risk for stress-induced eating to contribute to their obesity. PMID- 22051366 TI - Beverage intake in low-income parent-child dyads. AB - Beverage consumption adds to daily energy intake and often exceeds the recommended amount for discretionary energy. Previous research has shown that children are consuming sugar-sweetened beverages (SSB) in greater frequency and the relationship between parent-child dyads in beverage consumption is meaningful due to the parental influence on the development of beverage consumption behaviors. In particular, low-income families are at greater risk for obesity and higher levels of SSB consumption. The current investigation assessed habitual beverage intake among low-income parent-child dyads (N=95) with children between the ages of 9-17 years. The sample (46% African American; 45% Caucasian) had a mean body mass index (BMI) for the parents of 31.8+/-8.9 kg/m(2), while the mean BMI percentile for age and gender for the children was 70.3+/-31.3. Both parents and children consumed fewer nutrient-dense beverages and more energy-dense beverages than the recommended amount. The mean daily energy intake from beverages was 451+/-236 kcal for the parents and 457+/-237 kcal for the children. Correlations between parent-child dyad intake was also evident, identifying parents as potential role models and gatekeepers of the home food environment. Future interventions to prevent childhood obesity in low-income populations should address beverage intake, particularly SSB consumption, and determine the degree to which this behavior is learned behavior in the home. PMID- 22051367 TI - Measurement invariance of the Eating Attitudes Test-26 in Caucasian and Hispanic women. AB - To determine whether the EAT-26 functions similarly in Caucasian and Hispanic samples, the current study investigated the factor structure of the Eating Attitudes Test (EAT-26) in 235 undergraduate Caucasian (53.6%) and Hispanic (46.4%) women, and tested for measurement invariance across the two samples. A Confirmatory Factor Analysis (CFA) of the original 3-factor structure of the EAT resulted in a poor fit in both the Caucasian and Hispanic samples. We then performed a CFA using a previously discovered 4-factor, 16-item structure. This abbreviated measure was a good fit in both the Caucasian and Hispanic samples, and the model was invariant across all dimensions tested. The 16-item EAT is a better-fitting measure in Caucasian and Hispanic women than the commonly used EAT 26. This replicates an earlier finding and generalizes those conclusions to a Hispanic sample. PMID- 22051368 TI - Assessing rumination in eating disorders: principal component analysis of a minimally modified ruminative response scale. AB - A process account of eating disorders (EDs) (Park et al., in press-a) proposes that preoccupation with ruminative themes of eating, weight and shape may be important in ED maintenance. No self-report measure exists to capture disorder specific rumination in EDs. 275 healthy participants rated rumination items and completed self-report measures of ED symptoms, depression and anxiety. Principal component analysis revealed two factors, reflection and brooding. The final nine item Ruminative Response Scale for Eating Disorders (RRS-ED) demonstrated good convergent and discriminant validity and test-retest reliability. The psychometric properties were replicated in an anorexia nervosa sample. The findings support the notion that rumination in EDs is distinct from rumination in depression and is not adequately captured by existing measures. PMID- 22051369 TI - The relation between the lack of control attributional style for indulgent food consumption and bulimic symptoms. AB - OBJECTIVE: The study examined the potential link between the lack of control attributional style for indulgent food consumption and bulimic symptoms. METHOD: One hundred and 77 undergraduates (145 female; mean age=19 years-2 months) were administered the Eating Attributional Style Questionnaire and the Sterling Eating Disorder Scales across a five-month period. RESULTS: SEM analyses confirmed that: (1) uncontrollability attributions for indulgent food consumption were concurrently associated with bulimic symptoms, and (2) external locus of control and uncontrollability attributions for indulgent food consumption predicted changes in bulimic symptoms. CONCLUSIONS: The findings yielded support for the conclusion that the lack of control attributional style for indulgent food consumption is a probable cause of bulimic symptoms. PMID- 22051370 TI - Driven exercise among treatment-seeking youth with eating disorders. AB - PURPOSE: This study evaluated the prevalence and clinical significance of driven exercise (DE) in treatment-seeking youth. METHODS: Participants were 380 consecutive referrals to a pediatric eating disorder program (90.8% female; M age=14.9+/-2.2). Spearman's rho correlations examined the relation between DE frequency, and Beck Depression Inventory (BDI) and Eating Disorders Examination (EDE) Global Severity scores. ANOVA compared those reporting only DE, only vomiting, or both DE and vomiting on the aforementioned measures. RESULTS: 51.3% of participants (n=193) reported DE in the past 3 months, with an average of 21.8 (SD=32.6) episodes. Frequency of DE was related to EDE global severity score (Spearman's rho=.46; p<.001) and BDI Total Score (Spearman's rho=.33; p<.001). Participants reporting both vomiting and DE had the highest EDE global severity and BDI total scores. CONCLUSIONS: DE is associated with greater eating disorder and depressive symptomatology, especially when paired with vomiting. The findings highlight the importance of assessing for DE in youth presenting for eating disorder treatment. PMID- 22051371 TI - Knowledge, attitude and practice of women in Campinas, Sao Paulo, Brazil with respect to physical exercise in pregnancy: a descriptive study. AB - BACKGROUND: Pregnancy is a good time to develop healthy lifestyle habits including regular exercise and good nutrition. Programs of physical exercise for pregnant women have been recommended; however, there are few references on this subject in the literature. The objective of this study was to evaluate the knowledge, attitude and practice of pregnant women with respect to appropriate physical exercise during pregnancy, and also to investigate why some women do not exercise during pregnancy. METHODS: A descriptive study was conducted in which 161 women of 18 to 45 years of age were interviewed in the third trimester of pregnancy. These women were receiving prenatal care at National Health Service (SUS) primary healthcare units and had no pathologies for which physical exercise would constitute a risk. The women were selected at an ultrasonography clinic accredited to the SUS in Campinas, Sao Paulo. A previously elaborated knowledge, attitude and practice (KAP) questionnaire was used to collect data, which were then stored in an Epinfo database. Statistical analysis was conducted using Pearson's chi-square test and Fisher's exact test to evaluate the association between the study variables (p < 0.05). RESULTS: Almost two-thirds (65.6%) of the women were sufficiently informed about the practice of physical exercise during pregnancy and the vast majority (93.8%) was in favor of it. Nevertheless, only just over 20% of the women in this sample exercised adequately. Significant associations were found between an adequate knowledge of physical exercise during pregnancy and education level (p = 0.0014) and between the adequate practice of physical exercise during pregnancy and having had fewer pregnancies (p = 0.0001). Lack of time and feeling tired and uncomfortable were the principal reasons given by the women for not exercising. CONCLUSION: These results suggest that women's knowledge concerning the practice of physical exercise during pregnancy is reasonable and their attitude is favorable; however, relatively few actually exercise during pregnancy. PMID- 22051372 TI - Clinical ocular findings in cows with malignant catarrhal fever: ocular disease progression and outcome in 25 cases (2007-2010). AB - OBJECTIVE: To describe the ocular clinical signs in a group of cows diagnosed with sheep associated malignant catarrhal fever (MCF), and to investigate a possible correlation between the severity and progression of certain typical clinical signs and disease outcome. PROCEDURE: This prospective study involved cows diagnosed with MCF between 2007 and 2010, and included cows enrolled in a larger clinical trial. Signalment of affected cows, presence and progression of ocular lesions, as well as disease outcome were recorded. Cows were divided into two groups based on the disease outcome: (1) survival and (2) nonsurvival. The degree of corneal edema at first examination was statistically compared between groups. The progression of corneal edema, uveitis and the examining ophthalmologists' subjective assessment of disease progression between the first and last examination were also compared between groups. RESULTS: Twenty-five cows (22 F, 3 M) of six different breeds and one mixed breed were included. Median age was 21 months (range 8-113). Ten cows survived, 13 cows were euthanized, and two died. No statistical association was identified between the degree of corneal edema at the first examination and the disease outcome. Deterioration of corneal edema was not noticed in any of the surviving animals. Anterior uveitis improved in all 10 surviving cows. CONCLUSIONS: The degree of corneal edema at first examination had no prognostic value for the disease outcome. The results of this study suggest that the progression of corneal edema correlates well with disease outcome, and that nonimprovement of uveitis is a bad prognostic sign. PMID- 22051373 TI - Cytotoxic and anthelmintic potential of crude saponins isolated from Achillea Wilhelmsii C. Koch and Teucrium Stocksianum boiss. AB - BACKGROUND: Saponins isolated from plant sources have a number of traditional and industrial applications. Saponins have pharmacological effects like anti inflammatory, molluscicidal, antimicrobial, antispasmodic, antidiabetic, anticancer, anticonvulsant, anthelmintic, antitussive and cytotoxic activities. The current work describes the anthelmintic and cytotoxic activities of crude saponins of Achillea Wilhelmsii and Teucrium Stocksianum as these plants are rich with saponins. METHODS: Brine shrimp cytotoxic activity of crude saponins was determined by Meyer et al. (1982) at test concentrations of 1000 MUg/ml, 100 MUg/ml, 10 MUg/ml, 7.5 MUg/ml, 5.0 MUg/ml, 2.5 MUg/ml and 1.25 MUg/ml. Percentage mortality of test concentrations was determined. Similarly, in vitro anthelmintic activity was determined against roundworms, tapeworms and earthworms. Albendazole and piperazine citrate at concentration 10 mg/ml were used as standard anthelmintic drugs. RESULTS: Crude saponins of Achillea wilhelmsii (CSA) and Teucrium stocksianum (CST) had, respectively, cytotoxic activity with LC50 values 2.3+/-0.16 and 5.23+/-0. 34 MUg/ml. For in vitro anthelmintic activity, time for paralysis and death of parasites (parasiticidal activity) was noted. At concentration 40 mg/ml, crude saponins of Achillea wilhelmsii are 1.96 and 2.12 times more potent than albendazole against Pheretima posthuma and Raillietina spiralis, respectively. Similarly, at concentration 40 mg/ml, crude saponins of Teucrium stocksianum (CST) has 1.89, 1.96 and 1.37 times more parasiticidal activity than albendazole against Pheretima posthuma, Raillietina spiralis and Ascardia galli, respectively. CONCLUSION: Crude saponins of Achillea wilhelmsii and Teucrium stocksianum have cytotoxic and anthelmintic activity. The crude saponins may be excellent sources of cytotoxic and anthelmintic constituents that warrant its isolation and purification for new drug development. PMID- 22051374 TI - Regulation of chemotropic guidance of nerve growth cones by microRNA. AB - BACKGROUND: The small non-coding microRNAs play an important role in development by regulating protein translation, but their involvement in axon guidance is unknown. Here, we investigated the role of microRNA-134 (miR-134) in chemotropic guidance of nerve growth cones. RESULTS: We found that miR-134 is highly expressed in the neural tube of Xenopus embryos. Fluorescent in situ hybridization also showed that miR-134 is enriched in the growth cones of Xenopus spinal neurons in culture. Importantly, overexpression of miR-134 mimics or antisense inhibitors blocked protein synthesis (PS)-dependent attractive responses of Xenopus growth cones to a gradient of brain-derived neurotrophic factor (BDNF). However, miR-134 mimics or inhibitors had no effect on PS independent bidirectional responses of Xenopus growth cones to bone morphogenic protein 7 (BMP7). Our data further showed that Xenopus LIM kinase 1 (Xlimk1) mRNA is a potential target of miR-134 regulation. CONCLUSIONS: These findings demonstrate a role for miR-134 in translation-dependent guidance of nerve growth cones. Different guidance cues may act through distinct signaling pathways to elicit PS-dependent and -independent mechanisms to steer growth cones in response to a wide array of spatiotemporal cues during development. PMID- 22051375 TI - Lost in folding space? Comparing four variants of the thermodynamic model for RNA secondary structure prediction. AB - BACKGROUND: Many bioinformatics tools for RNA secondary structure analysis are based on a thermodynamic model of RNA folding. They predict a single, "optimal" structure by free energy minimization, they enumerate near-optimal structures, they compute base pair probabilities and dot plots, representative structures of different abstract shapes, or Boltzmann probabilities of structures and shapes. Although all programs refer to the same physical model, they implement it with considerable variation for different tasks, and little is known about the effects of heuristic assumptions and model simplifications used by the programs on the outcome of the analysis. RESULTS: We extract four different models of the thermodynamic folding space which underlie the programs RNAFOLD, RNASHAPES, and RNASUBOPT. Their differences lie within the details of the energy model and the granularity of the folding space. We implement probabilistic shape analysis for all models, and introduce the shape probability shift as a robust measure of model similarity. Using four data sets derived from experimentally solved structures, we provide a quantitative evaluation of the model differences. CONCLUSIONS: We find that search space granularity affects the computed shape probabilities less than the over- or underapproximation of free energy by a simplified energy model. Still, the approximations perform similar enough to implementations of the full model to justify their continued use in settings where computational constraints call for simpler algorithms. On the side, we observe that the rarely used level 2 shapes, which predict the complete arrangement of helices, multiloops, internal loops and bulges, include the "true" shape in a rather small number of predicted high probability shapes. This calls for an investigation of new strategies to extract high probability members from the (very large) level 2 shape space of an RNA sequence. We provide implementations of all four models, written in a declarative style that makes them easy to be modified. Based on our study, future work on thermodynamic RNA folding may make a choice of model based on our empirical data. It can take our implementations as a starting point for further program development. PMID- 22051376 TI - Properties of BoAGE2, a second N-acetyl-D-glucosamine 2-epimerase from Bacteroides ovatus ATCC 8483. AB - N-Acyl-D-Glucosamine 2-epimerase (AGE) catalyzes the reversible epimerization between N-acetyl-D-mannosamine (ManNAc) and N-acetyl-D-glucosamine (GlcNAc). Bacteroides ovatus ATCC 8483 shows 3 putative genes for AGE activity (BACOVA_00274, BACOVA_01795 and BACOVA_01816). The BACOVA_00274 gene encodes an AGE (BoAGE1) with strong similarity to the AGE previously characterized in Bacteroides fragilis. Interestingly, the BACOVA_01816 gene (BoAGE2) shares 57% identity with Anabaena sp. CH1 AGE, but has an extra 27-amino acid tag sequence in the N-terminal. When cloned and expressed in Escherichia coli Rosetta (DE3)pLys, BACOVA_01816 was able to convert ManNAc into GlcNAc and vice versa. It was stable over a broad range of pHs and its activity was enhanced by ATP (20 MUM). The incubation with ATP stabilized its structure, raising its melting temperature by about 8 degrees C. In addition, the catalytic efficiency for ManNAc synthesis was higher than that for GlcNAc synthesis. These characteristics make BoAGE2 a promising biocatalyst for sialic acid production using cheap GlcNAc as starting material. BoAGE2 could be considered a Renin-binding Protein and its interaction with renin was studied for the first time in a prokaryotic AGE. Surprisingly, renin activated BoAGE2, an effect which is contrary to that described for mammalian AGE and unrelated with the unique N-terminal tag, since a mutant without this tag was also activated by renin. When BoAGE2 sequence was compared with other related (real and putative) AGE described in the databases, it was seen that AGE enzymes can be divided in 3 different groups. The relationship between these groups is also discussed. PMID- 22051377 TI - Effect of onion-type multilamellar liposomes on Trametes versicolor laccase activity and stability. AB - Trametes versicolor laccase was encapsulated into onion-type, lipid-based multilamellar vesicles (MLVs). When encapsulated, laccase was isolated from the assay medium but was still active once freed from its capsule. The encapsulation efficiency was larger than 65% at 25 degrees C and 37 degrees C and decreased to 55% by introducing 140 mM NaCl into the buffered medium (pH = 4.5). MLVs were shown to drastically improve both laccase stability and activity. At 25 degrees C, laccase activity was doubled in the presence of MLVs. At 37 degrees C in the salt-free medium, the half-life time of laccase was increased from 2 hr 30-65 h without and with MLVs, respectively. This effect was even more pronounced in the salted medium where laccase activity was unchanged for 6 days in the presence of MLVs. These beneficial effects were attributed to the immobilization of laccase onto MLV surface. Laccase activity as well as stability was notably shown to be directly correlated to MLV stability. PMID- 22051378 TI - Molecular identification of the sperm selection involved porcine sperm binding glycoprotein (SBG) as deleted in malignant brain tumors 1 (DMBT1). AB - Porcine sperm binding glycoprotein (SBG) is involved in sperm-oviduct interaction. Here we use mass spectrometry to identify SBG, finding peptides corresponding to deleted in malignant brain tumors 1 (DMBT1), at scavenger receptor cysteine-rich (SRCR) and CUB domains. RT-PCR allowed the cloning of unique sequences, belonging to porcine DMBT1. Western blot and immunofluorescence of oviductal tissues using anti-SBG and anti-hDMBT1 antibodies showed identical results. The biochemical characteristics of both proteins are coincident. We conclude that porcine SBG is an oviductal form of DMBT1, and thus assign this protein a novel location and function. PMID- 22051380 TI - Endothelial development taking shape. AB - Blood vessel development is a vital process during embryonic development, during tissue growth, regeneration and disease processes in the adult. In the past decade researchers have begun to unravel basic molecular mechanisms that regulate the formation of vascular lumen, sprouting angiogenesis, fusion of vessels, and pruning of the vascular plexus. The understanding of the biology of these angiogenic processes is increasingly driven through studies on vascular development at the cellular resolution. Single cell analysis in vivo, advanced genetic tools and the widespread use of powerful animal models combined with improved imaging possibilities are delivering new insights into endothelial cell form, function and behavior angiogenesis. Moreover, the combination of in silico modeling and experimentation including dynamic imaging promotes insights into higher level cooperative behavior leading to functional patterning of vascular networks. Here we summarize recent concepts and advances in the field of vascular development, focusing in detail on the endothelial cell. PMID- 22051379 TI - A distinctive translocation carcinoma of the kidney; "rosette forming," t(6;11), HMB45-positive renal tumor: a histomorphologic, immunohistochemical, ultrastructural, and molecular genetic study of 4 cases. AB - To date, only a few cases of "rosette forming t(6;11), HMB45-positive renal carcinoma" have been published. In this article, we contribute further data on 4 cases of this rare entity. Patients were 3 women and 1 man with an age range of 20 to 54 years (median, 23 years). Follow-up (range, 3-5 years; median, 4 years) did not reveal any metastatic events or recurrences. All tumors were well circumscribed and mostly encapsulated with homogeneous gray to tan cut surfaces. No necrosis was seen. All tumors displayed a solid or solid/alveolar architecture and contained occasionally long and branching tubular structures composed of discohesive neoplastic cells and pseudorosettes. The presence of pseudorosettes was a constant finding, but the number of pseudorosettes varied significantly among cases. All cases displayed focal immunoreactivity for the melanocytic marker HMB45, cathepsin K, and vimentin. Melan A, tyrosinase, cytokeratins, CD10, and microphthalmia transcription factor were each positive in 3 of 4 cases. On ultrastructural examination, numerous electron-dense secretory cytoplasmic granules with some resemblance to melanosomes were identified. The pseudorosettes were composed of reduplicated basement membrane material surrounded by small lymphocyte-like neoplastic cells. Using reverse transcription polymerase chain reaction, 2 tumors were positive for the Alpha-TFEB fusion transcript. The presence of the translocation t(6;11)(Alpha-TFEB) was confirmed in 2 analyzed cases. No von Hippel-Lindau tumor suppressor gene mutation, promotor methylation or loss of heterozygosity of 3p was found. Losses of part of chromosome 1 and chromosome 22 were found in one case. PMID- 22051381 TI - The history and evolution of hand transplantation. AB - Hand transplantation has proven itself to be a viable treatment option for upper extremity reconstruction. It has grown through advancements in several critical areas: microsurgery, transplant immunology, and hand surgery. The field has also benefited from a global effort with active transplant centers in 3 different continents. The early struggles and breakthroughs of hand transplantation's past have shaped and formed its current state. This article traces the events of the modern era of hand transplantation. PMID- 22051382 TI - World experience after more than a decade of clinical hand transplantation: update on the French program. AB - The first hand transplantation was realized in Lyon and the results achieved in this case showed the feasibility of the surgical technique, the efficacy of the immunosuppressive protocol, the limited adverse effects and the importance of a patient's compliance and rehabilitation to ensure graft viability and functional recovery. Based on these findings and the positive results achieved in other single hand transplants realized around the world the authors performed also the first double hand transplantation, then followed by other four cases. The recipients received the same immunosuppressive treatment including tacrolimus, prednisone, mycophenolate mofetil and antithymocyte globulins for induction, nevertheless they showed some episodes of acute rejection episodes which reversed after a prompt treatment. All the bilateral hand grafted patients showed a relevant sensorimotor recovery particularly of sensibility and activity of intrinsic muscles. They were able to perform the majority of daily activities and to lead a normal social life. On the basis of the authors' experience the results achieved in hand allotransplantation are very encouraging as major adverse effects due to surgery and immunosuppressive regimen did not occur and patients' quality of life improved considerably. PMID- 22051383 TI - World experience after more than a decade of clinical hand transplantation: update from the Louisville hand transplant program. AB - In the last 12 years, the Louisville CTA program has screened more than 600 interested hand transplant candidates and has transplanted 6 patients with 7 hand allografts. The program is a collaborative effort between the surgeons and staff of Kleinert, Kutz and Associates, Jewish Hospital and St. Mary's Healthcare, the Christine M. Kleinert Institute, and the University of Louisville. The functional outcome and long-term results of clinical hand transplantation have exceeded initial expectations both within the program and in the community at large. This report summarizes the successes and challenges of the Louisville CTA experience in composite tissue allotransplantation. PMID- 22051384 TI - World experience after more than a decade of clinical hand transplantation: update on the Innsbruck program. AB - Patients who have lost a hand or upper extremity face many challenges in everyday life. For some patients, reconstructive hand transplantation represents a reasonable option for anatomic reconstruction, restoring prehensile function with sensation and allowing them to regain daily living independence. The first clinical case of bilateral hand transplantation at University Hospital Innsbruck was realized on March 17th, 2000. A decade later, a total of 7 hands and forearms were transplanted in 4 patients. This article review the clinical courses of 3 bilateral hand transplant recipients and highlights psychological aspects on reconstructive hand transplantation with special regard to unilateral/bilateral transplantation. PMID- 22051385 TI - World experience after more than a decade of clinical hand transplantation: update on the Polish program. AB - It has been demonstrated over the past decade that the generally achieved functional outcomes of patients after hand transplantation (HTx) are better than those of equivalent replantations. However, HTx should be performed in specialized centers with Institutional Review Board-approved transplantation programs. In Poland such requirements are fulfilled by The Subdepartment of Replantation of Limbs of St. Jadwiga Hospital in Trzebnica. A main emphasis of this subdepartment is to make the very involved process of donor recruitment, recipient screening, surgery, and postoperative treatment fully transparent. This article summarizes the experience of this center with HTx over the past 5 years. PMID- 22051386 TI - The Spanish experience with hand, forearm, and arm transplantation. AB - This article summarizes the findings from 3 recipients of hand allografts, including a description of the preparatory surgery and the transplant and secondary procedures to enhance the function of the hand, forearm, and arm allografts. The study focuses on the complications and disability reported by each patient, with a minimum follow-up of 2 years. The few complications were controlled successfully with medical treatment. Hand transplantation is a major reconstructive procedure that requires careful medical follow-up. The authors provide the first report of a significant improvement in disabilities of the upper limb as a result of hand allotransplantation. PMID- 22051387 TI - Functional outcome after hand and forearm transplantation: what can be achieved? AB - The first successful hand transplant in the modern era of reconstructive transplantation was performed in 1998. Since then, more than 65 hand and upper limb transplantations have been performed around the globe, with encouraging results. The main goal of all upper limb transplantations is to enhance the patient's quality of life. The transplant must be successfully integrated into the patient's body and self-image and the recipient should be satisfied with the recovery of sensitivity and muscle function of the new limb. To achieve these goals, a proper and thorough design of the rehabilitation regimen is of critical importance. PMID- 22051388 TI - Immunosuppressive protocols and immunological challenges related to hand transplantation. AB - There are many immunological challenges related to hand transplantation. Curbing the immune system's ability to effectively mount an immune response against the graft is the goal. As the various components of the immune response are defined and their mechanisms of action delineated, more specific immunosuppressive agents and protocols have been developed. Complications related to immunosuppression in hand transplant recipients are similar to incidences among solid organ recipients. With longer follow-up, the increased cardiovascular risk factors or the development of a neoplasm will likely cause mortality. Standardizing immunosuppression in hand transplantation with the long-term goal of minimization is critically needed. PMID- 22051389 TI - Acute and chronic rejection in upper extremity transplantation: what have we learned? AB - To date, 78 upper extremity transplants have been performed in 55 recipients around the world. The purpose of this article is to provide an overview of acute and chronic rejection (CR) and to summarize collective insights in upper extremity transplantation. To date, almost all patients experienced AR that is pathophysiologically similar to that in solid organs. The spectre of chronic rejection is just emerging. Upper extremity transplantation has significant potential as a reconstructive option only if efforts are invested in strategies to reduce risks of prolonged immunosuppression and in approaches to better diagnose, monitor and treat AR and CR. PMID- 22051391 TI - Favoring the risk-benefit balance for upper extremity transplantation--the Pittsburgh Protocol. AB - Upper extremity transplantation is an innovative reconstructive strategy with potential of immediate clinical application and the most near-term pay-off for select amputees, allowing reintegration into employment and society. Routine applicability and widespread impact of such strategies for the upper extremity amputees with devastating limb loss could be enabled by implementation of cellular therapies that integrate and unify the concepts of transplant tolerance induction with those of reconstructive transplantation. Such therapies offer the promise of minimizing the risks, maximizing the benefits and optimizing outcomes of these innovative procedures. PMID- 22051392 TI - Surgical and technical aspects of hand transplantation: is it just another replant? AB - The ultimate goal of hand allotransplantation is to achieve graft survival and useful long-term function. To achieve these goals, selection of the appropriate patient, detailed preoperative planning, and precise surgical technique are of paramount importance. Transplantation should be reserved for motivated consenting adults in good general heath, who are psychologically stable and have failed a trial of prosthetic use. While the key surgical steps of transplantation are similar to those of replantation, there are major differences. This article describes the steps in hand allotransplantation, and the importance of patient selection as well as preoperative and postoperative care. PMID- 22051393 TI - Development of an upper extremity transplant program. AB - Starting a hand transplant program poses tremendous challenges. Solid organ transplantation and hand replantation are time-tested procedures and are now standard of care. Hand transplantation is the amalgamation of the scientific principles of reconstructive surgery and the concepts of organ transplantation. Thus, for any hand transplant program to be successful, there must be collaboration within a multidisciplinary team comprising a core group of hand and transplant surgeons. Such a joint effort can overcome the challenges that are inherent in a complex therapeutic option that integrates different disciplines and organizations during the planning, procedural, and posttransplant phases. PMID- 22051390 TI - Clinical strategies to enhance nerve regeneration in composite tissue allotransplantation. AB - Reinnervation of a hand transplant ultimately dictates functional recovery but provides a significant regenerative challenge. This article highlights interventions to enhance nerve regeneration through acceleration of axonal regeneration or augmentation of Schwann cell support and discuss their relevance to composite tissue allotransplantation. Surgical techniques that may be performed at the time of transplantation to optimize intrinsic muscle recovery- including appropriate alignment of ulnar nerve motor and sensory components, transfer of the distal anterior interosseous nerve to the recurrent motor branch of the median nerve, and prophylactic release of potential nerve entrapment points--are also presented. PMID- 22051394 TI - Recipient screening and selection: who is the right candidate for hand transplantation. AB - Hand transplantation is an elective non-life saving but quality of life-giving surgery for good candidates that is not without risk. Patient screening and selection is the most critical element to successful transplantation outcomes and cannot be overemphasized in terms of importance in the overall scheme of an active composite tissue allotransplantation (CTA) program. This article discusses the various criteria that are important in the selection of patients for CTA. PMID- 22051395 TI - Donor-related issues in hand transplantation. AB - The policies and procedures for solid-organ donation, under the auspices of the Organ Procurement and Transplantation Network, currently cannot be applied to hand donation, because a hand allograft is considered a tissue in the United States and is under the jurisdiction of the Food and Drug Administration. Hand transplant centers have developed their own protocols. This article discusses the unique elements of such protocols, including training and education, the consent process, the necessary recipient and donor data, donor management, and operating room procedures. Candidate listing, allocation, and oversight of hand donation in the future are also discussed. PMID- 22051396 TI - Ethical, financial, and policy considerations in hand transplantation. AB - Currently, more than 65 hand transplants have been performed with studies demonstrating favorable cosmetic and functional outcomes and cortical reintegration of the transplanted hand. Due to such favorable outcomes, many view hand transplant as a potential gold standard for treatment of a double amputee. However, ethical debate continues regarding risks and benefits of this nonlifesaving procedure. Clinicians, patients, and society must agree on whether hand transplantation is ethical and affordable. If a decision is made to transplant a hand, this must be performed in a dedicated center that facilitates integration of multiple specialists, ethicists, pharmacists, and rehabilitationists. PMID- 22051397 TI - Arthroscopic dorsal capsuloligamentous repair in chronic scapholunate ligament tears. AB - This article discusses the preliminary results of treatment of chronic scapholunate lesions by arthroscopic dorsal capsuloligamentous repair, which does not require open exposure of the wrist capsule. Thirty six patients underwent arthroscopically assisted dorsal capsuloplasties. Sixteen had percutaneous pinning. Mean follow-up was at 11.4 months. The average arc of motion was 105 degrees preoperatively and 120 degrees postoperatively. The average grip strength attained 92% of the contralateral side. Most of the results were excellent-to good. Seven professional athletes returned to preinjury level. Arthroscopic dorsal capsuloligamentous repair is a promising option, but a longer follow-up is necessary to confirm these results. PMID- 22051398 TI - Hand transplantation. PMID- 22051399 TI - Multilocus phylogeographical analysis of Trypanosoma (Megatrypanum) genotypes from sympatric cattle and water buffalo populations supports evolutionary host constraint and close phylogenetic relationships with genotypes found in other ruminants. AB - Species of the subgenus Trypanosoma (Megatrypanum) have been reported in cattle and other domestic and wild ruminants worldwide. A previous study in Brazil found at least four genotypes infecting cattle (Bos taurus), but only one in water buffalo (Bubalus bubalis). However, the small number of isolates examined from buffalo, all inhabiting nearby areas, has precluded evaluation of their diversity, host associations and geographical structure. To address these questions, we evaluated the genetic diversity and phylogeographical patterns of 25 isolates from water buffalo and 28 from cattle from four separate locations in Brazil and Venezuela. Multigene phylogenetic analyses of ssrRNA, internal transcribed spacer of rDNA (ITSrDNA), 5SrRNA, glycosomal glyceraldehyde 3 phosphate dehydrogenase (gGAPDH), mitochondrial cytochrome b (Cyt b), spliced leader (SL) and cathepsin L-like (CATL) sequences positioned all isolates from sympatric and allopatric buffalo populations into the highly homogeneous genotype TthIA, while the cattle isolates were assigned to three different genotypes, all distinct from TthIA. Polymorphisms in all of these sequences separated the trypanosomes infecting water buffalo, cattle, sheep, antelope and deer, and suggested that they correspond to separate species. Congruent phylogenies inferred with all genes indicated a predominant clonal structure of the genotypes. The multilocus analysis revealed one monophyletic assemblage formed exclusively by trypanosomes of ruminants, which corresponds to the subgenus T. (Megatrypanum). The high degree of host specificity, evidenced by genotypes exclusive to each ruminant species and lack of genotype shared by different host species, suggested that the evolutionary history of trypanosomes of this subgenus was strongly constrained by their ruminant hosts. However, incongruence between ruminant and trypanosome phylogenies did not support host-parasite co-evolution, indicating that host switches have occurred across ruminants followed by divergences, giving rise to new trypanosome genotypes adapted exclusively to one host species. PMID- 22051400 TI - Abundance-variance and abundance-occupancy relationships in a marine host parasite system: the importance of taxonomy and ecology of transmission. AB - Abundance-occupancy and abundance-variance relationships are two of the most general macroecological patterns capturing essential fundamentals of the structuring of species distributions and are widely documented for free-living animal and plant species populations at different spatial scales. However, empirical data for parasites have been gathered using appropriate sampling designs only recently. We performed analyses across species of the variation in infection parameters and patterns of aggregation of the most widespread parasites in the marine sparid fish Boops boops across seven localities of two marine biogeographical regions, the North East Atlantic and the Mediterranean. We used a large dataset of multiple population samples replicated over time for 20 parasite species and carried out assessments both intraspecifically and interspecifically, across taxonomic and ecological groupings. This taxonomically diverse complex of species representing five major metazoan higher taxa with differing transmission ecologies allowed us to assess the effect of taxonomic and ecological determinants on the abundance-occupancy and abundance-variance relationships in the model marine host-parasite system. The results revealed that: (i) a power function, relating spatial variance to mean abundance, represents a suitable model for the spatial distribution of the species; (ii) prevalence, abundance and the degree of spatial heterogeneity are true species characteristics and differ consistently between higher level taxonomic groupings; (iii) infection parameters and abundance-variance relationship are dependent on host specificity and regional distribution patterns of the parasites; and (iv) the observed infection parameters agree well with predictions from the epidemiological negative binomial abundance-occupancy model built on parameters of Taylor's power law both within and across species. PMID- 22051401 TI - Genetic diversity of Schistosoma japonicum miracidia from individual rodent hosts. AB - Schistosoma japonicum is an important parasite in terms of clinical, veterinary and socio-economic impacts, and rodents, a long neglected reservoir for the parasite, have recently been found to act as reservoir hosts in some endemic areas of China. Any difference in the host's biological characteristics and/or associated living habitats among rodents may result in different environments for parasites, possibly resulting in a specific population structure of parasites within hosts. Therefore knowledge of the genetic structure of parasites within individual rodents could improve our understanding of transmission dynamics and hence our ability to develop effective control strategies. In this study, we aimed to describe a host-specific structure for S. japonicum and its potential influencing factors. The results showed a significant genetic differentiation among hosts. Two factors, including sampling seasons and the number of miracidia genotyped per host, showed an effect on the genetic diversity of an infrapopulation through a univariable analysis but not a multivariable analysis. A possible scenario of clustered infection foci and the fact of multiple definitive host species, the latter of which is unique to S. japonicum compared with other schistosomes, were proposed to explain the observed results and practical implications for control strategies are recommended. PMID- 22051402 TI - [The geography of aging in atlantic Canada: analysis from the point of view of territorial disparities during 1981-2006]. AB - Following the example of other Canadian provinces, those in Atlantic Canada are affected, albeit to a lesser degree, by the increase in the number of persons aged 65 or over, a trend that we can define as gerontogrowth. In addition, this region of Canada seems particularly affected by the trend of an aging population, that is, the rise in the proportion of people in the total population aged 65 or more. For example, on a national scale, New Brunswick is the third oldest province according to the last five-year period (2001-2006), having advanced from the fourth position it held between 1981 and 2001 and from the fifth position occupied between 1971 and 1981. In addition, these trends evolve in different manners in different places, contrasts that are strongest at the regional and local level. The goal of this article is to examine the strength of these disparities during the period 1981 to 2006 and to identify some potential solutions for a territorial development strategy for seniors. PMID- 22051403 TI - Understanding why women adopt and sustain home water treatment: insights from the Malawi antenatal care program. AB - In many settings in Africa, social marketing has proven more successful in generating brand recognition for chlorine water treatment products than in promoting their use. To promote household use of one such product in Malawi, WaterGuard, the Ministry of Health (MOH) and Population Services International (PSI) distributed free hygiene kits that included WaterGuard to pregnant women attending antenatal clinics in 2007. Follow-up surveys documented a sustained increase in WaterGuard use three years after the initial intervention. In 2010, PATH (www.path.org) conducted qualitative research on the factors motivating women to adopt, sustain, or discontinue use. To provide context, interviews were also conducted with their friends, relatives, and husbands. Interviews revealed that sustained use of WaterGuard does not necessarily imply consistent use. Most respondents reported switching back and forth between WaterGuard and stock chlorine distributed for free by the government, and many treated water seasonally rather than year-round. Qualitative findings suggest that two program strategies strongly influenced women's decisions to adopt, purchase, and continue using WaterGuard. First, positive, ongoing contacts with health care workers, especially during home visits, raised awareness of the need to treat water, encouraged trial use, and supported continuing use. Second, an extended free trial of the product overcame initial cost barriers and allowed women and their families to experience the health benefits of WaterGuard, appreciate its value and relevance to their lives, and get used to its taste. Social support-from like minded relatives, friends, neighbors, health care workers, husbands, and children was also a critical factor that promoted consistent, ongoing use of WaterGuard. The findings confirm the importance of interpersonal communication in prompting adoption of household water treatment and suggest that consumers assess the perceived value of a product, not simply its cost. Further research is planned to investigate questions raised about patterns of ongoing use. PMID- 22051404 TI - Proteomic study of malignant pleural mesothelioma by laser microdissection and two-dimensional difference gel electrophoresis identified cathepsin D as a novel candidate for a differential diagnosis biomarker. AB - To investigate the proteomic background of malignancies of the pleura, we examined and compared the proteomic profile of malignant pleural mesothelioma (MPM)(10 cases), lung adenocarcinoma (11 cases), squamous cell carcinoma of the lung (13 cases), pleomorphic carcinoma of the lung (3 cases) and synovial sarcoma (6 cases). Cellular proteins were extracted from specific populations of tumor cells recovered by laser microdissection. The extracted proteins were labeled with CyDye DIGE Fluor saturation dyes and subjected to two-dimensional difference gel electrophoresis (2D-DIGE) using a large format electrophoresis device. Among 3875 protein spots observed, the intensity of 332 was significantly different (Wilcoxon p value less than 0.05) and with more than two-fold inter-sample-group average difference between the different histology groups. Among these 332, 282 were annotated by LC-MS/MS and included known biomarker proteins for MPM, such as calretinin, as well as proteins previously uncharacterized in MPM. Tissue microarray immunohistochemistry revealed that the expression of cathepsin D was lower in MPM than in lung adenocarcinoma (15% vs. 44% of cases respectively in immunohistochemistry). In conclusion, we examined the protein expression profile of MPM and other lung malignancies, and identified cathepsin D to distinguish MPM from most popular lung cancer such as lung adenocarcinoma. PMID- 22051405 TI - Point: balloon versus strut brachytherapy-which device offers the most dose modulation capability and normal tissue sparing? PMID- 22051406 TI - Counterpoint: the device with the most dose modulation capacity. PMID- 22051409 TI - Combined transperineal implant and external beam radiation for the treatment of prostate cancer: a large patient cohort in the community setting. AB - PURPOSE: Treatment of prostate cancer using higher doses of external beam radiation (EBRT) has been shown to improve results, but there are toxicity concerns with further dose escalation. A treatment option to safely increase total dose to the prostate includes combination therapy using EBRT and low-dose rate transperineal brachytherapy seed implant. Our purpose was to report the results of combined modality therapy from a single institution in the community setting. METHODS AND MATERIALS: Retrospective review from single institution in the community setting. All patients were treated with a combination of EBRT followed by low-dose-rate brachytherapy seed placement. RESULTS: A total of 824 patients were analyzed with a median followup of 5.5 years, all censored patients had a minimum followup of 2 years. A total of 588 patients received hormone therapy before or concurrent with the radiation. Three hundred twenty-nine patients had low-risk disease, 300 patients had intermediate-risk disease, and 195 patients had high-risk disease. Five-year overall survivals were 86.1%, 85.0%, and 82.5% for low-, intermediate-, and high-risk patients. Five-year actuarial biochemical relapse-free survivals (bRFSs) were 85.4%, 83.2%, and 79.6% for low-, intermediate-, and high-risk patients. High-risk patients who received hormonal therapy had an improved bRFS vs. patients not receiving hormones. CONCLUSIONS: Combination treatment using brachytherapy and EBRT is well tolerated, with acceptable overall survival and bRFS rates and should be considered a standard treatment option for patients. Hormones should be considered for high-risk patients. PMID- 22051410 TI - FT-IR spectroscopy and DFT calculation study on the solvent effects of benzaldehyde in organic solvents. AB - FT-IR spectra of benzaldehyde in 11 different organic solvents were recorded and analyzed. The density functional theory (DFT) B3LYP/6-31G* method was chosen to calculate the infrared spectrum of benzaldehyde in gaseous state. The electrostatic effects of different solvents in benzaldehyde solutions were calculated using DFT with the self-consistent isodensity polarizable continuum model (SCI-PCM). Two remarkable carbonyl (C=O) peaks of benzaldehyde were observed by FT-IR in alcohol solvents, which were caused by different hydrogen bond species and explained by ab initio calculation. The results showed that the combination of SCI-PCM model and ab initio calculation could give excellent agreements with FT-IR spectra of title compound in solutions. PMID- 22051411 TI - Quantum chemistry study of molecular structure and vibrational spectrum of naproxen. AB - The purpose of this research was to compare the performance of different DFT methods at different basis sets in predicting geometry and vibrational spectrum of naproxen. The molecular structure and infrared spectrum of naproxen was studied. Quantum chemical calculations using density functional theory (DFT) with functions LSDA, B3LYP, B3PW91, BPV86, mPW1PW91 and PBEPBE at various basis set levels (LANL2DZ, SDD, 3-21G, 6-31G, 6-311G and STO-3G) were performed. The computed result indicates that LSDA/6-311G level is distinctly superior to all the remaining DFT methods in predicting molecular structure of naproxen. The vibrational spectral analysis indicates the LSDA/3-21G level and LSDA/6-311G level are both better than the other methods at all the remaining basis sets. PMID- 22051412 TI - Binding interactions of water-soluble camptothecin derivatives with bovine serum albumin. AB - In this study, the binding interactions of the water-soluble camptothecin derivatives hydroxycamptothecin (10-HCPT), topotecan (TPT), and camptothecin quaternary salt (CPT8), to bovine serum albumin (BSA) were determined using fluorescence spectra and UV-vis spectra. The results revealed that the fluorescence of BSA was strongly quenched by the binding of camptothecin derivatives to BSA. The quenching mechanism of the camptothecin derivatives was found to be static according to the Stern-Volmer equation. The binding constant and binding sites were confirmed by fluorescence quenching spectra. The thermodynamic parameters Gibbs free energy change (DeltaG<0), enthalpy change (DeltaH>0), and entropy change (DeltaS>0) implied that the interaction process was spontaneous and endothermic, and the interaction forces between camptothecin compounds and BSA were found to be hydrophobic. According to Foster non radioactive energy transfer, the binding distances between 10-HCPT, TPT, and CPT8, and BSA were determined to be 1.73nm, 1.63nm, and 1.61nm, respectively. The synchronous fluorescence spectra confirmed that the camptothecin compounds cannot cause conformational changes in BSA. A rapid and sensitive method for determining the binding interaction between water-soluble camptothecin derivatives and BSA was established based on these principles of fluorescence quenching. PMID- 22051413 TI - Temperature-dependent Raman and IR studies of multiferroic MnWO4 doped with Ni2+ ions. AB - Temperature-dependent Raman and IR studies of MnWO(4) crystal doped with Ni(2+) ions were performed in the 4.2-300 K range. These studies were complemented by magnetization and specific heat measurements in the 2-100K range, which revealed that MnWO(4) crystal doped with Ni(2+) ions exhibits two phase transitions at 13.9 and 12.5K. Temperature evolution of Raman wavenumbers and linewidths revealed anomalous behaviour at low temperatures. These anomalies have been attributed to spin-phonon coupling, which appear due to onset of antiferromagnetic spin ordering. The observed anomalies extend above T(N)=13.9 K. This behaviour is consistent with the fact that MnWO(4) is a moderately magnetically frustrated material. PMID- 22051414 TI - Enhanced photoluminescence of Gd2O3:Eu3+ nanophosphors with alkali (M=Li+, Na+, K+) metal ion co-doping. AB - Gd(1.95)Eu(0.04)M(0.01)O(3) (M=Li(+), Na(+), K(+)) nanophosphors have been synthesized by a low temperature solution combustion (LSC) method. Powder X-ray diffraction pattern (PXRD), scanning electron microscopy (SEM), UV-vis and photoluminescence (PL) measurements were carried out to characterize their structural and luminescent properties. The excitation and emission spectra indicated that the phosphor could be well excited by UV light (243 nm) and emit red light about 612 nm. The effect of alkali co-dopant on PL properties has been examined. The results showed that incorporation of Li(+), Na(+) and K(+) in to Gd(2)O(3):Eu(3+) phosphor would lead to a remarkable increase of photoluminescence. The PL intensity of Gd(2)O(3):Eu(3+) phosphor was improved evidently by co-doping with Li(+) ions whose radius is less than that of Gd(3+) and hardly with Na(+), K(+) whose radius is larger than that of Gd(3+). The effect of co-dopants on enhanced luminescence was mainly regarded as the result of a suitable local distortion of crystal field surrounding the Eu(3+) activator. These results will play an important role in seeking some more effective co dopants. PMID- 22051415 TI - Experimental FTIR and theoretical studies of gallic acid-acetonitrile clusters. AB - Gallic acid (3,4,5-trihydroxybenzoic acid, GA) has many possible conformers depending on the orientations of its three OH and COOH groups. The biological activity of polyphenolic compounds has been demonstrated to depend on their conformational characteristics. Therefore, experimental FTIR and theoretical studies of the GA-solvent clusters were performed to investigate the possible most favored conformation of GA. Acetonitrile (ACN) was selected as the solvent since its spectrum did not interfere with the OH stretching bands of GA. Also of importance was that these OH groups, in addition to the carboxyl group, of the GA are the most likely groups to interact with receptors. The solution of GA in the ACN solution was measured and the complex OH bands were deconvoluted to four component bands. These component bands corresponded to the three OH bands on the benzene ring and a broad band which is a combination band of mainly the OH of the COOH group and the inter- and intramolecular H-bonds from the OH groups on the ring. The conformations, relative stabilities and vibrational analysis of the GA monomers and the GA-ACN clusters were investigated using the B3LYP/6 311++G(2d,2p) method. Conformational analysis of the GA monomer yielded four most possible conformers, GA-I, GA-II, GA-III and GA-IV. These conformers were subsequently used for the study of the GA:ACN clusters at the 1:1, 1:2 and 1:4 mole ratios. The IR spectra of the most stable structures of these clusters were simulated and the vibrational wavenumbers of the OH and C=O groups were compared with those from the experiment. The FTIR component bands were comparable to the computed OH bands of the GA-I-(ACN)(2), GA-IV-(ACN)(2) and GA-I-(ACN)(4) clusters. Furthermore, the C=O stretching bands and the bands in the regions of 1800-1000 cm(-1) obtained by computing and the experiment were similar for these clusters. Thus, GA-I and GA-IV are the most preferable conformations of GA in ACN and perhaps in the polar environment around the receptor sites of GA. PMID- 22051416 TI - A series of Ti(IV)/Ti(III) coordination polymers: structures and surface photoelectric properties. AB - Three titanium coordination polymers, {[Ti(SO(4))(2)(H(2)O)].0.5bipy.2H(2)O}(n)1, {[Ti1(SO(4))(2)(H(2)O)].[Ti2(SO(4))(2)(H(2)O)].bipy.5H(2)O}(n)2 and [Ti(tea)](n)3 (bipy=4,4'-bipyridine, H(3)tea=triethanolamine) were synthesized and characterized by IR, UV-Vis absorption spectra, TG analysis, X-ray single crystal diffraction and surface photovoltage spectroscopy (SPS). The surface photoelectric properties of titanium coordination polymers were discussed emphatically by the SPS. The results of single crystal diffraction indicate that polymers 1 and 2 possess 1D infinite structure bridged by SO(4)(2-) groups and coordinated water molecules and further connected into supramolecular structures by hydrogen bonds. Polymer 3 possesses 2D infinite structure bridged by weak sub coordinated Ti-O bonds. The results of SPS show that there are obvious photovoltage responses in the range of 300-500 nm, which indicates that they possess photoelectric conversion ability. The SPS of three titanium polymers were analyzed comparatively. It is found that the valence of central metal ions, coordination micro-environment and kinds of coordination atoms influence the results of the SPS. The SPS is associated with UV-Vis absorption spectra. PMID- 22051417 TI - Treatment with beta-blockers and incidence of post-traumatic stress disorder after cardiac surgery: a prospective observational study. AB - OBJECTIVE: The aim was to investigate perioperative factors associated with the development of post-traumatic stress disorder (PTSD) in patients who underwent cardiac surgery. DESIGN: Prospective observational study. SETTING: Single academic center. PARTICIPANTS: One hundred twenty-eight consecutive patients scheduled for elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were interviewed within the surgical unit 1 to 3 days before cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Six months after surgery, participants were mailed the modified version of the Posttraumatic Stress Symptom Inventory 10. Of the 71 patients who completed the questionnaire and mailed it back at follow-up, 14 (19.7%) received a diagnosis of PTSD. Seven of 13 female patients who were not treated with beta-blockers received a diagnosis of PTSD compared with 0 of 12 who were treated with beta-blockers (p = 0.005, Fisher exact test). In a general linear model, including sex and beta-blocker treatment as predictors, the Posttraumatic Stress Symptom Inventory 10 score was significantly predicted by beta-blockade (F = 4.74, p = 0.033), with a significant interaction between sex and beta-blockade (F = 9.72, p = 0.003). CONCLUSIONS: These findings suggest that the use of beta-blockers might be protective against the development of PTSD in women after cardiac surgery. PMID- 22051418 TI - Mitral annular nonplanarity: correlation between annular height/commissural width ratio and the nonplanarity angle. AB - OBJECTIVE: To compare two methods of mitral annular nonplanarity: the mathematically calculated annular height-to-commissural width ratio (AHCWR) and the echocardiographically derived nonplanarity angle. DESIGN: Prospective. SETTING: Tertiary care university hospital. INTERVENTIONS: Three-dimensional transesophageal echocardiography. PARTICIPANTS: Patients undergoing mitral valve surgery. MEASUREMENTS AND MAIN RESULTS: Using 3-dimensional transesophageal echocardiography, volumetric datasets were acquired from 22 patients undergoing mitral valve surgery. The intraoperative nonplanarity angle was calculated with Mitral Valve Assessment software (Tomtec GmbH, Munich, Germany). Furthermore, the datasets acquired during 3-dimensional transesophageal echocardiography were exported to Matlab software (MathWorks, Natick, MA), which was used to calculate the AHCWR. The nonplanarity angle was seen to correlate favorably with the AHCWR (r = 0.70). CONCLUSIONS: A favorable correlation was found between the nonplanarity angle and the AHCWR. This suggests that the nonplanarity angle can be used to assess mitral annular nonplanarity in a clinically feasible fashion. PMID- 22051419 TI - Levosimendan versus an intra-aortic balloon pump in high-risk cardiac patients. AB - OBJECTIVE: To test the hypothesis that levosimendan is more effective than intra aortic balloon pump (IABP) support in cardiac surgical patients with low left ventricular ejection fraction to decrease cardiac troponin I levels (primary endpoint) and improve hemodynamics. DESIGN: Prospective randomized trial. SETTING: Tertiary cardiothoracic referral center. PARTICIPANTS: Ninety patients with coronary artery disease and left ventricular ejection fraction <35% who underwent surgery with cardiopulmonary bypass. INTERVENTION: Patients were assigned randomly to 1 of 3 groups. Group A received a prophylactic IABP one day before surgery. Group B received a prophylactic IABP one day before surgery and a levosimendan infusion at a dose of 0.1 MUg/kg/min with an initial bolus (12 MUg/kg for 10 minutes) after anesthesia induction. Group C received a levosimendan infusion at a dose of 0.1 MUg/kg/min with an initial bolus (12 MUg/kg for 10 minutes) after anesthesia induction. Hemodynamic and biochemical data and rate of complications were analyzed. MEASUREMENTS AND MAIN RESULTS: The cardiac troponin I level in group C 6 hours after surgery was lower than in group A (p = 0.048). The cardiac index in group A was significantly lower than in groups B and C. The intensive care unit stay was significantly shorter in group C than in groups A and B (p = 0.001). The need for inotropic support, the rate of complications, and mortality among groups did not differ. CONCLUSIONS: The infusion of levosimendan after anesthesia induction in cardiac surgical patients contributes to lower cardiac troponin I levels and improved hemodynamics compared with a preoperative IABP. PMID- 22051420 TI - New British guidelines mandate ambulatory blood pressure monitoring to diagnose hypertension in all patients: not ready for prime time in the United States. PMID- 22051421 TI - The United Nations high level meeting addresses noncommunicable diseases, but where is hypertension? PMID- 22051422 TI - Management of cardiovascular risk factors is leaving the office: potential impact of telemedicine. AB - Effective control of hypertension and the other cardiovascular risk factors has been dependent on primary medical care as provided by family practitioners and internists. The progressive reduction in availability of primary care for adult populations in the United States threatens the likelihood of better control of the risk factors and potential loss of opportunity for prevention of cardiovascular disease. Recent progress has been made in the use of home blood pressure monitoring for improvement in classification of risk for hypertensive patients. Several studies establish the feasibility of home pressure monitoring combined with telemedicine for improving control of hypertension. Some studies have explored the role of self-care for adjustment of medication, as well. The potential growth of this strategy for effective control of hypertension with reduced need for face-to-face encounter time in primary care is a promising solution to the reduction in primary care providers. Management of hyperlipidemia and diabetes by telemedicine is also being explored, particularly for rural areas, but may also be effective in urban settings. Development of technology for home monitoring together with electronic communication to providers and mechanisms for education, feedback, and warnings offers a promising solution to the possible crisis in prevention of cardiovascular disease due to the loss of traditional primary care. PMID- 22051423 TI - Determinants of blood pressure response to low-salt intake in a healthy adult population. AB - Although the beneficial effects of lowering salt intake in hypertensive patients are widely appreciated, the impact of promoting dietary salt restriction for blood pressure (BP) reduction at the population level remains controversial. The authors used 24-hour ambulatory BP monitoring to characterize the determinants of systolic BP (SBP) response to low-salt intake in a large, relatively healthy Amish population. Patients received a high- and low-sodium diet for 6 days each, separated by a 6- to 14-day washout period. Variance component analysis was used to assess the association of several variables with SBP response to low-salt diet. Mean SBP was 0.7 +/- 5.8 mm Hg and 1.3 +/- 6.1 mm Hg lower on the low-salt compared with the high-salt diet during daytime (P=.008) and nighttime (P<.0001), respectively. SBP response to a low-salt diet was significantly associated with increasing age and pre-intervention SBP, in both daytime and nighttime, while the association with female sex and SBP response to cold pressor test (CPT) was significant only during nighttime. Our results suggest that salt reduction may have greater BP-lowering effects on women, older individuals, individuals with higher SBP, and individuals with higher SBP response to CPT. PMID- 22051424 TI - Blood pressure outcomes in patients receiving angiotensin II receptor blockers in primary care: a comparative effectiveness analysis from electronic medical record data. AB - The authors examined the comparative effectiveness of 4 angiotensin receptor blockers (ARBs) in patients with hypertension using a large electronic medical record database. Analysis of covariance and logistic multivariate regression models were used to estimate the blood pressure (BP) outcomes of 73,012 patients during 13 months of treatment with olmesartan, losartan, valsartan, and irbesartan. Results were adjusted by baseline BP, starting dose, year, age, sex, race, body mass index, comorbid conditions, and concomitant medications of patients. All ARBs led to sustained reductions in BP, but with significant differences in the magnitude of BP reduction. Raw mean systolic BP/diastolic BP reductions with losartan, valsartan, irbesartan, and olmesartan were 9.3/4.9 mm Hg, 10.4/5.6 mm Hg, 10.1/5.3 mm Hg, and 12.4/6.8 mm Hg, respectively. Adjusting for all covariates, the overall BP reductions with olmesartan were 1.88/0.86 mm Hg, 1.21/0.52 mm Hg, and 0.89/0.51 mm Hg greater than for losartan, valsartan, and irbesartan, respectively, and mean differences were higher for monotherapy: 2.43/1.16 mm Hg; 2.18/0.93 mm Hg; 1.44/0.91 mm Hg, respectively (all P values <.0001). Adjusted odds ratios of the JNC 7 goal attainment for losartan, valsartan, and irbesartan compared with olmesartan were 0.76, 0.86, and 0.91 (P<.05). Differences were also found in subpopulations: African Americans, diabetics, and obese/overweight patients but not all of these reached statistical significance. A broad choice of ARBs may be required to get patients to treatment goals. PMID- 22051425 TI - The dynamics of blood pressure and cognitive functioning: results from 6-year follow-up of an elderly cohort. AB - The association between blood pressure (BP) and cognitive functioning in the elderly is still under debate. Theoretically, high BP could either prevent or enhance cognitive impairment. The authors assessed the changes that took place in BP and cognitive functioning over 6 years. A total of 318 noninstitutional elderly (81% of the survivors) were re-evaluated. BP was measured and a cognitive test was performed. Elderly patients who had higher systolic BP (SBP) and scored lower on the Mini-Mental State Examination (MMSE) at baseline were less likely to survive. At follow-up, the proportion of patients with normal or normalized BP by treatment increased. Considerable changes in SBP were observed. Most cognitive functions declined during follow-up; however, decline in SBP was associated with better verbal fluency and memory. Both an increase and a decline in SBP were associated with better MMSE scores. Changes in diastolic BP (DBP) were less evident and DBP was not related to cognitive functioning. The current study demonstrates the importance of studying the dynamics of both BP and cognition over time. It appears that transition from hypertension to normotension improves cognitive functions. Survival processes may restrict the evaluation of the BP cognition interaction over time. PMID- 22051426 TI - Neurovascular decompression of the rostral ventrolateral medulla decreases blood pressure and sympathetic nerve activity in patients with refractory hypertension. AB - Recently, the authors experienced four patients who had refractory hypertension and neurovascular compression of the rostral ventrolateral medulla (RVLM). One of them, a 49-year-old woman, had undergone continuous intravenous drip injections of calcium channel blockers and beta-blockers for more than 3 years because of severe and refractory hypertension. The patients had undergone microvascular decompression (MVD) of the RVLM, and the changes in blood pressure (BP) and sympathetic nerve activities were recorded. In these patients, BP decreased to the normal range without any antihypertensive drugs 2 to 3 months after MVD. The tibial sympathetic nerve activities under resting and stress conditions significantly decreased, and plasma levels of norepinephrine, urinary levels of adrenaline, and plasma renin activity were also significantly decreased after MVD of RVLM. In some patients with refractory hypertension, arterial compression of the RVLM enhances sympathetic nerve activity and renin-angiotensin system to thereby increase BP. In these patients, the operative decompression of the RVLM could lower BP via restoration of sympathetic nerve activities and the renin angiotensin system. PMID- 22051427 TI - Accuracy of blood pressure measurements reported in an electronic medical record during routine primary care visits. AB - Electronic medical records (EMRs) allow for real-time access to blood pressure (BP) information on a population basis and improve identification and treatment of individuals with hypertension. Despite the potential uses of the data available from EMRs, relatively little research has examined the reliability of this data. To address this gap, the authors examined the reliability of BP taken at primary care visits and recorded in an EMR with those taken at a research study visit at which standard protocols were used to measure BP among all adults as well as by sex and age. Systolic BP (SBP) averaged 3.7 (17.3) points and diastolic BP (DBP) was 2.8 (10.6) points lower in the EMR than in the study visit across age and sex groups, with all differences statistically significant. For this cohort of patients with a diagnosis of hypertension, there was moderate correlation between BP measurements taken in clinic and at research. However, BP control for individuals, as defined by an SBP <140 mm Hg and DBP 90 mm Hg, differed by almost 25%. Known variability of BP and clinic procedures for measuring and recording BP may account for these differences. PMID- 22051428 TI - Nondrug interventions for treatment of hypertension. AB - The treatment of hypertension is no longer limited to the simple prescription of pharmaceuticals. For many patients, maximal medical therapy is insufficient to adequately treat refractory hypertension. In addition, some patients may prefer to explore therapies that do not involve drugs as an initial step. Utilizing our broadening understanding of the physiology of hypertension, new technology and interventions have been developed that allow for treatments that do not rely on medications. In addition, dietary supplements and modification, as well as herbal supplements, may be useful under the right circumstances. Lifestyle modification remains a necessary part of treatment for all patients with hypertension. This article will review the evidence behind some available nondrug interventions for the treatment of hypertension. PMID- 22051429 TI - "Environmental hypertensionology" the effects of environmental factors on blood pressure in clinical practice and research. AB - Blood pressure (BP) is affected by many environmental factors including ambient temperature, altitude, latitude, noise, and air pollutants. Given their pervasiveness, it is plausible that such factors may also have an impact on hypertension prevalence and control rates. Health care providers should be aware that the environment can play a significant role in altering BP. Although not among the established modifiable risk factors (eg, obesity) for hypertension, reducing exposures when pertinent should be considered to prevent or control hypertension. The authors provide a concise review of the evidence linking diverse environmental factors with BP and suggest an approach for incorporating this knowledge into clinical practice. The authors propose using the term environmental hypertensionology to refer to the study of the effects of environmental factors on BP in clinical and research settings. PMID- 22051430 TI - The role of magnesium in hypertension and cardiovascular disease. AB - Magnesium intake of 500 mg/d to 1000 mg/d may reduce blood pressure (BP) as much as 5.6/2.8 mm Hg. However, clinical studies have a wide range of BP reduction, with some showing no change in BP. The combination of increased intake of magnesium and potassium coupled with reduced sodium intake is more effective in reducing BP than single mineral intake and is often as effective as one antihypertensive drug in treating hypertension. Reducing intracellular sodium and calcium while increasing intracellular magnesium and potassium improves BP response. Magnesium also increases the effectiveness of all antihypertensive drug classes. It remains to be conclusively proven that cardiovascular disease such as coronary heart disease, ischemic stroke, and cardiac arrhythmias can be prevented or treated with magnesium intake. Preliminary evidence suggests that insulin sensitivity, hyperglycemia, diabetes mellitus, left ventricular hypertrophy, and dyslipidemia may be improved with increased magnesium intake. Various genetic defects in magnesium transport are associated with hypertension and possibly with cardiovascular disease. Oral magnesium acts as a natural calcium channel blocker, increases nitric oxide, improves endothelial dysfunction, and induces direct and indirect vasodilation. PMID- 22051431 TI - Reducing cardiorenal risk through combination therapy with a direct renin inhibitor. AB - Interruption of the renin-angiotensin-aldosterone system (RAAS) cascade with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or more recently direct renin inhibitors (DRIs) is a safe and effective antihypertensive strategy that is in routine clinical use. The clinical utility of these agents in cardiorenal end-organ protection is increasingly being recognized. Although both ACE inhibitors and ARBs demonstrate substantial benefit in patients with cardiovascular and/or renal disease, considerable evidence indicates that they only partially suppress the RAAS pathway due to feedback upregulation of plasma renin activity. With the goal of providing more comprehensive RAAS blockade, combination ACE inhibitor/ARB therapy has been evaluated. However, this approach has not shown the anticipated improvements in composite cardiovascular and renal outcomes and appears to be associated with significant toxicity. Due to a unique mechanism of action, the combination of a DRI with an ACE inhibitor or ARB may represent an effective end-organ-protective therapeutic strategy. PMID- 22051432 TI - Seasonal variability of blood pressure in California. PMID- 22051433 TI - Should patients with chronic kidney disease have an ambulatory BP monitor for accurate renal and cardiovascular risk assessment? PMID- 22051434 TI - Hypertension associated with angiogoenesis inhibitors: what do oncologists really do in daily routine? A small survey. PMID- 22051437 TI - Self-reported health status (EQ-5D) in adults with congenital heart disease. AB - PURPOSE: Today, more patients with congenital heart disease (CHD) reach adulthood. There are conflicting findings concerning the relationship between quality of life (QoL) or health state for adults with CHD and the complexity of their CHD. The aim of the study was, firstly, to compare the reported health status and health perception of adult patients with CHD and, secondly, to investigate what variables influenced the patients' health status and health perception. METHODS: Data from 1435 patients completing the EQ-5D questionnaire, which includes reported health status and health perception, were analyzed. RESULTS: Valid EQ-5D data were reported by 1274 patients, showing overall results indicating a good health status. Problems were most frequently reported in the dimension "pain/discomfort" (31.9%) and "anxiety/depression" (29.8%). Higher occurrence of problems were reported by patients with complex disease i.e. single ventricle (p<0.001) and by female patients (p<0.0001). Symptomatic patients reported a lower health status (p<0.0001) and a lower perceived health on EQ-VAS (p<0.0001). Of the asymptomatic patients, 20.5% nevertheless reported problems in "pain/discomfort" and 22.2% in the "anxiety/depression" dimension. CONCLUSION: The health status of adults with CHD is influenced by symptoms, NYHA classification, age and gender. Adults with CHD report a lower occurrence of problems in comparison to previously published results from a general population, but the importance of actively asking about the patient's experience is demonstrated by the high degree of asymptomatic patients reporting problems on EQ 5D. PMID- 22051438 TI - Promoting psychosocial well-being following a stroke: developing a theoretically and empirically sound complex intervention. AB - BACKGROUND: The psychosocial consequences of stroke are complex and comprehensive and include substantial and longlasting impacts on mood, identity, social relationships, return to work and quality of life. Many studies have explored possible interventions to prevent or treat psychosocial problems, but the results have generally been disappointing. Very few studies have provided adequate theoretical accounts of the mechanisms assumed to contribute to positive outcomes. OBJECTIVES: To describe the development of a psychosocial nursing intervention aimed at promoting psychosocial health and well-being and to stimulate dialogue about how to develop and report theoretically and empirically sound complex interventions in nursing. DESIGN: A systematic, stepwise approach was used, consistent with the framework recommended for developing and evaluating complex interventions by the UK Medical Research Council. DATA SOURCES: Systematic reviews of empirical studies regarding the psychosocial consequences and needs of patients following stroke; qualitative, experiential studies of stroke and stroke recovery; theories of psychosocial well-being, coping, life skills, narrative approaches to rehabilitation and guided self-determination. REVIEW METHODS: Each systematic review was examined to determine the major psychosocial challenges and needs experienced by stroke survivors, focusing on how these challenges and needs developed over the illness trajectory, how previous interventions had sought to address them and the effective mechanisms assumed to affect the level of success of interventions. Qualitative studies were examined to reveal the subjective experiences of stroke and stroke recovery, paying particular attention to the development of needs across time and context. A qualitative synthesis of the major characteristics of the trajectory of stroke rehabilitation and recovery during the first year was developed. Theories were examined to illuminate possible effective mechanisms and actions aimed at promoting psychosocial well-being during the stroke recovery process. RESULTS: A dialogue-based intervention comprising eight encounters between stroke survivors and trained health care workers was designed, based on narrative theories, empowerment philosophy and guided self determination. Worksheets and a guiding topical outline were developed to support the dialogue. CONCLUSIONS: The UK Medical Research Council framework facilitated the systematic development of an empirically and theoretically informed complex nursing intervention aimed at promoting post-stroke psychosocial well-being. PMID- 22051439 TI - Developing a healthy living intervention for people with early psychosis using the Medical Research Council's guidelines on complex interventions: phase 1 of the HELPER - InterACT programme. AB - BACKGROUND: Young people with early psychosis often gain a significant amount of weight after the initiation of anti-psychotic treatment. Despite the current policy guidance to develop and evaluate 'healthy living' interventions for people with psychosis there remains a paucity of research. Our aim was to develop an acceptable, feasible, culturally sensitive and potentially effective 'healthy living' intervention, specifically for young people with early psychosis. METHODS: Using the Medical Research Council guidelines for developing and evaluating complex interventions we conducted a number of studies to devise a 'healthy living' intervention. We used a 'top down' (published evidence), bottom up (stakeholder perspectives) approach, which included updating a systematic review, identifying a theoretical basis for the intervention, exploring the perspectives of service users and health professionals, and identifying key cultural issues. The results of these studies were synthesised to determine the content and delivery of the intervention. RESULTS: The intervention developed comprised eight individual sessions to be delivered by a support time recovery worker over a 12 month period with emphasis on individualised action plans to facilitate participatory exercise and changes in diet. To optimise engagement, choice and self management a booklet and website were developed to provide participants with educational advice, healthy eating recipes and other materials. CONCLUSION: Using the Medical Research Council guidelines we have developed a potentially effective, feasible and acceptable 'healthy living' intervention for people with psychosis using early intervention services in the UK. PMID- 22051440 TI - No evidence of the Shiga toxin-producing E. coli O104:H4 outbreak strain or enteroaggregative E. coli (EAEC) found in cattle faeces in northern Germany, the hotspot of the 2011 HUS outbreak area. AB - BACKGROUND: Ruminants, in particular bovines, are the primary reservoir of Shiga toxin-producing E. coli (STEC), but whole genome analyses of the current German ESBL-producing O104:H4 outbreak strain of sequence type (ST) 678 showed this strain to be highly similar to enteroaggregative E. coli (EAEC). Strains of the EAEC pathotype are basically adapted to the human host. To clarify whether in contrast to this paradigm, the O104:H4 outbreak strain and/or EAEC may also be able to colonize ruminants, we screened a total of 2.000 colonies from faecal samples of 100 cattle from 34 different farms - all located in the HUS outbreak region of Northern Germany - for genes associated with the O104:H4 HUS outbreak strain (stx2, terD, rfbO104, fliCH4), STEC (stx1, stx2, escV), EAEC (pAA, aggR, astA), and ESBL-production (blaCTX-M, blaTEM, blaSHV). RESULTS: The faecal samples contained neither the HUS outbreak strain nor any EAEC. As the current outbreak strain belongs to ST678 and displays an en-teroaggregative and ESBL producing phenotype, we additionally screened selected strains for ST678 as well as the aggregative adhesion pattern in HEp-2 cells. However, we were unable to find any strains belonging to ST678 or showing an aggregative adhesion pattern. A high percentage of animals (28%) shed STEC, corroborating previous knowl-edge and thereby proving the validity of our study. One of the STEC also harboured the LEE pathogenicity island. In addition, eleven animals shed ESBL-producing E. coli. CONCLUSIONS: While we are aware of the limitations of our survey, our data support the theory, that, in contrast to other Shiga-toxin producing E. coli, cattle are not the reservoir for the O104:H4 outbreak strain or other EAEC, but that the outbreak strain seems to be adapted to humans or might have yet another reservoir, raising new questions about the epidemiology of STEC O104:H4. PMID- 22051441 TI - Prior contest experience exerts a long-term influence on subsequent winner and loser effects. AB - INTRODUCTION: Animals are capable of using information from recent experiences to modify subsequent behavioral responses. Animals' ability or propensity to modify their behavior in the light of new information has repeatedly been shown to correlate with, or be influenced by, either their intrinsic competitive ability or their dominance experience - an influence which can be long-lasting. Using a mangrove killifish, Kryptolebias marmoratus, as the study organism, we investigated whether and if so how the effect of a winning or a losing experience one day prior to a dyadic contest was modulated by both competitive ability measured two months previously and a winning or losing experience forced on the contestants one month previously. RESULTS: Winning/losing experience forced on the fish one month previously affected how they utilized information from their winning/losing experience one day before Test Day: Individuals that were randomly assigned a losing experience one month previously were more susceptible to the influence of their 1-day winning/losing experience than those assigned a winning experience. Competitive ability measured two months previously, winning/losing experience from one month previously and the winning/losing experience received one day previously all significantly influenced the fish's contest behaviors on Test Day, although only 2-month competitive ability significantly influenced escalation duration, indicating that it was still a good index for the fish's competitive ability two months later. CONCLUSIONS: These results suggest that the value to the fish of information from a recent win or loss depends on the outcome of their past contests and show that contest experience has a long-term effect on contest behavior. PMID- 22051442 TI - Reconstruction of a massive lower limb soft-tissue defect by giant free DIEAP flap. AB - Treatment of high-velocity trauma of the lower limb is often challenging in its nature, especially when dealing with extensive soft-tissue loss, underlying bone fractures and vascular lesions. The main goal in this surgery is the preservation of a functional and sensitive limb, or maximal functional length of the stump when dealing with limb amputations. We present a case report of a reconstruction of a complex massive soft-tissue defect of a lower limb by a giant free deep inferior epigastric artery perforator (DIEAP) flap. Classification and treatment options for massive lower limb defects are discussed. The free DIEAP flap is another valuable option for massive soft-tissue lower limb reconstructions and limb salvage procedures. It provides massive amounts of soft tissue with minimal donor-site morbidity, which is easily amenable for secondary corrections. PMID- 22051443 TI - Treatment of complex ischial pressure sores with free partial lateral latissimus dorsi musculocutaneous flaps in paraplegic patients. AB - In paraplegic patients dependent on their upper body for mobility, the latissimus dorsi muscle is generally unacceptable for microsurgical reconstruction of complex ischial defect. To avoid total muscle function loss, a portion of the lateral latissimus dorsi musculocutaneous flap can instead be harvested. From February 1999 to March 2009, 11 paraplegic patients with complex ischial pressure sores were prospectively recruited. The reconstruction was performed using a free partial lateral latissimus dorsi musculocutaneous flap. The follow-up period ranged from 18 to 114 months (mean, 60 months). All flaps survived postoperatively. No recurrence occurred in our series. All patients experienced various degrees of back tightness, shoulder weakness and limited shoulder motion since surgery, which were relieved within 9 months. The free partial lateral latissimus dorsi musculocutaneous flap can be a good alternative for covering severe infected ischial defect. Shoulder functional deficits will lessen over time and normal function will be regained gradually. PMID- 22051444 TI - A case of congenital unilateral amastia. AB - Numerous reports have been published regarding the reconstruction of the breast, but the majority of these reports focus on breast reconstruction for defects caused by the removal of breast cancers. The authors treated a rare case of unilateral amastia where a 54-year-old female had a complete absence of the breast on one side, though the breast on the other side was intact. The defect was reconstructed successfully with a transverse rectus abdominis myocutaneous flap (TRAM) flap. The present study introduces this rare case with reference to past reports of amastia. PMID- 22051445 TI - A novel dendrimeric peptide induces high level neutralizing antibodies against classical swine fever virus in rabbits. AB - The amino acid sequence (TAVSPTTLR, 829-837aa) on the glycoprotein E2 of classical swine fever virus (CSFV) is a conserved and linear neutralizing epitope. In the present study, two peptides were constructed based the core sequence of this neutralizing epitope, the dendrimeric peptide (Th-B(4)) containing four copies of B cell epitope fused to one copy of promiscuous T helper (Th) cell epitope and the peptide Th-B containing a single copy of B cell epitope fused to one copy of Th cell epitope. The dendrimeric peptide Th-B(4) elicited high titers of neutralizing antibodies as detected in an indirect ELISA, blocking ELISA and neutralization test and induced a complete protection against CSFV C strain in rabbits. The Th-B elicited low titers of neutralizing antibodies and did not induce a protection in rabbits. These results suggest that the dendrimeric peptide Th-B(4) may be a promising marker vaccine candidate against CSFV and the multimerization is a requirement for development of a peptide vaccine. PMID- 22051446 TI - Genome analysis of Betanodavirus from cultured marine fish species in Malaysia. AB - Betanodavirus is the causative agent of the viral nervous necrosis (VNN) or viral encephalopathy and retinopathy disease in marine fish. This disease is responsible for most of the mass mortalities that occurred in marine fish hatcheries in Malaysia. The genome of this virus consists of two positive-sense RNA molecules which are the RNA1 and RNA2. The RNA1 molecule contains the RdRp gene which encodes for the RNA-dependent RNA polymerase and the RNA2 molecule contains the Cp gene which encodes for the viral coat protein. In this study, total RNAs were extracted from 32 fish specimens representing the four most cultured marine fish species in Malaysia. The fish specimens were collected from different hatcheries and aquaculture farms in Malaysia. The RNA1 was successfully amplified using three pairs of overlapping PCR primers whereas the RNA2 was amplified using a pair of primers. The nucleotide analysis of RdRp gene revealed that the Betanodavirus in Malaysia were 94.5-99.7% similar to the RGNNV genotype, 79.8-82.1% similar to SJNNV genotype, 81.5-82.4% similar to BFNNV genotype and 79.8-80.7% similar to TPNNV genotype. However, they showed lower similarities to FHV (9.4-14.2%) and BBV (7.2-15.7%), respectively. Similarly, the Cp gene revealed that the viruses showed high nucleotide similarity to RGNNV (95.9 99.8%), SJNNV (72.2-77.4%), BFNNV (80.9-83.5%), TPNNV (77.2-78.1%) and TNV (75.1 76.5%). However, as in the RdRp gene, the coat protein gene was highly dissimilar to FHV (3.0%) and BBV (2.6-4.1%), respectively. Based on the genome analysis, the Betanodavirus infecting cultured marine fish species in Malaysia belong to the RGNNV genotype. However, the phylogenetic analysis of the genes revealed that the viruses can be further divided into nine sub-groups. This has been expected since various marine fish species of different origins are cultured in Malaysia. PMID- 22051447 TI - Vessel remodelling, pregnancy hormones and extravillous trophoblast function. AB - During early human pregnancy, extravillous trophoblast (EVT) cells from the placenta invade the uterine decidual spiral arterioles and mediate the remodelling of these vessels such that a low pressure, high blood flow can be supplied to the placenta. This is essential to facilitate normal growth and development of the foetus. Defects in remodelling can manifest as the serious pregnancy complication pre-eclampsia. During the period of vessel remodelling three key pregnancy-associated hormones, human chorionic gonadotrophin (hCG), progesterone (P(4)) and oestradiol (E(2)), are found in high concentrations at the maternal-foetal interface. Potentially these hormones may control EVT movement and thus act as regulators of vessel remodelling. This review will discuss what is known about how these hormones affect EVT proliferation, migration and invasion during vascular remodelling and the potential relationship between hCG, P(4), E(2) and the development of pre-eclampsia. PMID- 22051448 TI - Hind limb suspension and long-chain omega-3 PUFA increase mRNA endocannabinoid system levels in skeletal muscle. AB - Muscle disuse has numerous physiological consequences that end up with significant catabolic metabolism and ultimately tissue atrophy. What is not known is how muscle atrophy affects the endocannabinoid (EC) system. Arachidonic acid (AA) is the substrate for anandamide (AEA) and 2-arachidonylgycerol (2-AG), which act as agonists for cannabinoid receptors CB1 and CB2 found in muscle. Diets with n-3 polyunsaturated fatty acids (PUFA) have been shown to reduce tissue levels of AA, AEA and 2-AG. Therefore, we hypothesized that hind limb suspension (HS) induced muscle atrophy and intake of n-3 PUFA will change mRNA levels of the EC system. Mice were randomized and assigned to a moderate n-3 PUFA [11.7 g/kg eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA)], high n-3 PUFA (17.6 g/kg EPA+DHA) or control diets for 12 days and then subjected to HS or continued weight bearing (WB) for 14 days. HS resulted in body weight, epididymal fat pad and quadriceps muscle loss compared to WB. Compared to WB, HS had greater mRNA levels of AEA and 2-AG synthesis enzymes and CB2 in the atrophied quadriceps muscle. The high n-3 PUFA diet resulted in greater mRNA levels of EC synthesis enzymes, and CB1 and CB2. The higher mRNA levels for EC with HS and dietary n-3 PUFA suggest that muscle disuse and diet induce changes in the EC system to sensitize muscle in response to metabolic and physiological consequences of atrophy. PMID- 22051449 TI - Salmonellosis and charter tourism: epidemiology and trends of imported human cases to Norway from the Canary Islands and Thailand, 1994-2008. AB - More than 70% of reported human Salmonella infections in Norway are infected abroad. The Canary Islands and Thailand are two of the most popular charter tourist destinations for Norwegians. Using surveillance data for the years 1994 2008, and denominator data on travel to the Canary Islands 2000-2008 and to Thailand 1997-2008, we present the epidemiology and trends of Salmonella infections in Norwegian tourists to these destinations. We found a declining trend in risk of salmonellosis in tourists returning from the Canary Islands, and a change in serovar distribution in travellers to Thailand with more S. Enteritidis infections, similar to that observed in Western European countries. The use of denominator data is important when studying risk of travel-related disease, as surveillance data tend to reflect travel activity more than the risk. Infections among tourists do not always affect the local residents and therefore may not be detected by local public health authorities. Sharing knowledge on the epidemiology of infections in tourists could be useful for observation of changes in trends in the countries visited, and in future outbreak investigations. PMID- 22051451 TI - The challenges of leadership in the new era of health care. PMID- 22051450 TI - Tiotropium Handihaler and the risk of cardio- or cerebrovascular events and mortality in patients with COPD. AB - BACKGROUND: Tiotropium has been associated with an increased risk of mortality and/or cardiovascular events. Recent data from RCTs suggests tiotropium Handihaler to be safe, but its safety has not yet been fully investigated under real-life circumstances. METHODS: We conducted 2 nested case-control studies in a COPD cohort from the Dutch IPCI database. In the first case-control study, cases had a cardiovascular or cerebrovascular endpoint (CCVE): stroke and transient ischemic attack (TIA), myocardial infarction, heart failure and/or ventricular arrhythmia. In the second, cases were all patients who died. Cases were matched to controls on age, sex and index date. Conditional logistic regression analysis was used to calculate adjusted odds ratios (OR(adj)) with 95% confidence intervals (CI) for tiotropium vs. long-acting beta-agonists (LABA). RESULTS: Within a cohort of 6788 COPD patients, 784 CCVE's and 1032 deaths were reported. Compared to current LABA use, use of tiotropium Handihaler was neither associated with an increased risk of a CCVE (OR(adj) 0.89, 95% 0.55-1.44) nor with an increased risk of death (OR(adj) 0.79, 95% CI 0.49-1.28). CONCLUSIONS: In real life, use of tiotropium Handihaler in COPD patients is not associated with an increased risk of a CCVE or mortality compared to LABA. PMID- 22051452 TI - Always read the fine print. PMID- 22051453 TI - Informing patients about risks and benefits of radiology examinations utilizing ionizing radiation: a legal and moral dilemma. PMID- 22051454 TI - The mores of radiology. PMID- 22051455 TI - MOC for dollars. PMID- 22051456 TI - ACR Appropriateness Criteria(r) right lower quadrant pain--suspected appendicitis. AB - The diagnostic imaging of patients presenting with right lower quadrant pain and suspected appendicitis may be organized according to age and gender and to the presence or absence of "classic" signs and symptoms of acute appendicitis. Among adult patients presenting with clinical signs of acute appendicitis, the sensitivity and specificity of CT are greater than those of ultrasound, with improved performance when CT is performed with intravenous contrast. The use of rectal contrast has been associated with decreased time in the emergency department. Computed tomography has also been shown to reduce cost and negative appendectomy rates. Both CT and ultrasound are also effective in the identification of causes of right lower quadrant pain unrelated to appendicitis. Among pediatric patients, the sensitivity and specificity of graded-compression ultrasound can approach those of CT, without the use of ionizing radiation. Performing MRI after inconclusive ultrasound in pregnant patients has been associated with sensitivity and specificity of 80% to 86% and 97% to 99%, respectively. The ACR Appropriateness Criteria((r)) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID- 22051457 TI - Ionizing radiation in abdominal CT: unindicated multiphase scans are an important source of medically unnecessary exposure. AB - PURPOSE: CT radiation exposure has come under increasing scrutiny because of dramatically increased utilization. Multiphase CT studies (repeated scanning before and after contrast injection) are a potentially important, overlooked source of medically unnecessary radiation because of the dose-multiplier effect of extra phases. The purpose of this study was to determine the frequency of unindicated multiphase scanning and resultant excess radiation exposure in a sample referral population. METHODS: Abdominal and pelvic CT examinations (n = 500) performed at outside institutions submitted for tertiary interpretation were retrospectively reviewed for (1) the appropriateness of each phase on the basis of clinical indication and ACR Appropriateness Criteria((r)) and (2) per phase and total radiation effective dose. RESULTS: A total of 978 phases were performed in 500 patients; 52.8% (264 of 500) received phases that were not supported by ACR criteria. Overall, 35.8% of phases (350 of 978) were unindicated, most commonly being delayed imaging (272 of 350). The mean overall total radiation effective dose per patient was 25.8 mSv (95% confidence interval, 24.2-27.5 mSv). The mean effective dose for unindicated phases was 13.1 mSv (95% confidence interval, 12.3-14.0 mSv), resulting in a mean excess effective dose of 16.8 mSv (95% confidence interval, 15.5-18.3 mSv) per patient. Unindicated radiation constituted 33.3% of the total radiation effective dose in this population. Radiation effective doses exceeding 50 mSv were found in 21.2% of patients (106 of 500). CONCLUSIONS: The results of this study suggest that a large proportion of patients undergoing abdominal and pelvic CT scanning receive unindicated additional phases that add substantial excess radiation dose with no associated clinical benefit. PMID- 22051458 TI - Common incidental findings on MDCT: survey of radiologist recommendations for patient management. AB - PURPOSE: The aim of this study was to evaluate for agreement with respect to how radiologists report incidental findings encountered on CT. METHODS: A multiple choice survey was designed to query radiologists about how they handle 12 incidental findings on body CT, assuming the patient is a 45-year-old woman with no history of malignancy. Included were a 1-cm thyroid nodule, a 5-mm noncalcified lung nodule, coronary artery calcification, a 2-cm adrenal nodule, a 2-cm pancreatic cyst, a 1-cm enhancing liver lesion, a 2-cm high-density renal cyst, short-segment small bowel intussusception, a 1-cm splenic cyst, focal gallbladder wall calcification, and a 3-cm ovarian cyst in both a premenopausal woman and a postmenopausal woman. Choices ranged from "do not report" to advising interventional procedures tailored to the organ. Surveys were administered to body CT attending radiologists at 3 academic institutions. RESULTS: Twenty-seven radiologists completed the survey. The mean experience level was 15.7 years after training. Seventy percent or greater agreement on interpretation was identified for only 6 findings: recommend ultrasound for a 1-cm thyroid nodule, recommend ultrasound for a 3-cm cyst in postmenopausal woman, follow Fleischner Society recommendations for a 5-mm lung nodule, describe only coronary calcification, and describe as likely benign both short-segment small bowel intussusception and a 1 cm splenic cyst. CONCLUSIONS: Agreement is lacking, both across institutions and within departments, for the management of 6 commonly encountered incidental findings on body CT. Individual departments should develop internal guidelines to ensure consistent recommendations based on existing evidence. PMID- 22051459 TI - Medical imaging data reconciliation, part 3: reconciliation of historical and current radiology report data. AB - Correlation of historical imaging and radiology report data with the current imaging data set is a critical step in the radiologic interpretation process and, if incomplete, can adversely affect diagnostic accuracy. In its current form, the extraction and analysis of historical imaging and report data is limited by manual workflow, inefficient data organization, and a lack of imaging and report data integration. The reconciliation of historical and contemporaneous radiology report data provides an opportunity to improve the consistency, completeness, and accuracy of radiology report data, while providing opportunities to automate workflow related to data extraction, interpretation, and peer review. The derived data analytics can in turn be used to facilitate physician consultations, education and training, and proactive intervention in the event of report discrepancies. PMID- 22051460 TI - Noncardiac point-of-care ultrasound by nonradiologist physicians: how widespread is it? AB - PURPOSE: The use of point-of-care (POC) ultrasound by nonradiologist physicians has recently been advocated. The aim of this study was to see how widespread this practice is. METHODS: The Medicare Part B databases for 2004 to 2009 were used. Global and professional component claims for noncardiac ultrasound were tabulated, and utilization rates per 1,000 beneficiaries were calculated. Provider specialty was determined. Utilization rates of ultrasound by radiologists and other specialists were compared, and changes over the years were studied. RESULTS: In 2009, 425.3 Medicare noncardiac ultrasound examinations per 1,000 beneficiaries were performed (+21% since 2004). Of these, radiologists performed 233.7 (55%), and another 15.6 (4%) were done at independent diagnostic testing facilities, for which provider specialty could not be determined. The remaining 175.7 (41%) constituted POC ultrasound by nonradiologists. Between 2004 and 2009, radiologists' utilization rate increased by 17%, compared with 28% for nonradiologists. Radiologists' market share of noncardiac ultrasound was 56.6% in 2004 and 54.9% in 2009. Other major specialties involved in POC ultrasound and their 2009 rates per 1,000 and percentage increases since 2004 were cardiology (39.7 [+60%]), vascular surgery (34.9 [+36%]), primary care (27.2 [+11%]), general surgery (24.2 [+8%]), and urology (22.3 [+12%]). CONCLUSIONS: Between 2004 and 2009, there was a 21% increase in the overall utilization rate of noncardiac ultrasound. Point-of-care ultrasound by nonradiologists amounted to 41% of all studies done in 2009. Multiple nonradiologic specialties are involved, but radiologists' involvement is far higher than any other single specialty. Radiologists' ultrasound market share remained relatively stable between 2004 and 2009. PMID- 22051461 TI - Failure to notify reportable test results: significance in medical malpractice. AB - BACKGROUND: Diagnostic physicians generally acknowledge their responsibility to notify referring clinicians whenever examinations demonstrate urgent or unexpected findings. During the past decade, clinicians have ordered dramatically greater numbers of diagnostic examinations. One study demonstrated that between 1996 and 2003, malpractice payments related to diagnosis increased by approximately 40%. Communication failures are a prominent cause of action in medical malpractice litigation. The aims of this study were to (1) define the magnitude of malpractice costs related to communication failures in test result notification and (2) determine if these costs are increasing significantly. EVALUATION: Linear regression analysis of National Practitioner Data Bank claims data from 1991 to 2009 suggested that claims payments increased at the national level by an average of $4.7 million annually (95% confidence interval, $2.98 million to $6.37 million). Controlled Risk Insurance Company/Risk Management Foundation claims data for 2004 to 2008 indicate that communication failures played a role, accounting for 4% of cases by volume and 7% of the total cost. DISCUSSION: Faile communication of clinical data constitutes an increasing proportion of medical malpractice payments. The increase in cases may reflect expectations of more reliable notification of medical data. Another explanation may be that the remarkable growth in diagnostic test volume has led to a corresponding increase in reportable results. If notification reliability remained unchanged, this increased volume would predict more failed notifications. CONCLUSIONS: There is increased risk for malpractice litigation resulting from diagnostic test result notification. The advent of semiautomated critical test result management systems may improve notification reliability, improve workflow and patient safety, and, when necessary, provide legal documentation. PMID- 22051462 TI - Greening radiology. AB - PURPOSE: Reducing energy consumption has increased in importance with rising energy prices and funding cutbacks. With the introduction of electronic medical records on the rise in all fields of medicine, there will be a large jump in the number of computers in health care. Radiologist have the unique opportunity, as technological leaders, to direct energy efficiency measures as a means of cost savings and the reduction of airborne by-products from energy production to improve patients' lives. The aim of this study was to assess the many workstations and monitors throughout the authors' department to determine their electrical consumption and cost. METHODS: Equipment was monitored using an electricity meter during both active and standby states. Cost per kilowatt-hour was calculated at $0.11, not including taxes and fees. RESULTS: Any given monitor left on 24/7 would annually consume between 49.5 and 1,399.84 kWh, costing from $5.45 to $153.98. A single workstation left on 24/7 would use 455.65 to 2,358.72 kWh, costing from $59.91 to $259.46. In aggregate, all workstations and monitors would use approximately 137,759.54 kWh, costing $15,153.55. If all equipment were shut down after an 8-hour workday, the department would consume about 32,633.64 kWh, costing $3,589.70 thereby saving 83,866.6 kWh and $9,225.33. Although computers in the remainder of the hospital may use less energy than workstations, this serves as a predictive model for potential energy consumption and cost. CONCLUSIONS: With the increasing necessity of cost savings and energy reduction, this small and simple step, implemented hospital-wide, will lead to much larger cost savings across institutions. PMID- 22051463 TI - Residents' educational needs during transition into radiation oncology residency. AB - PURPOSE: The aim of this study was to assess current practices, strengths, and deficiencies in the orientation process for incoming radiation oncology (RO) residents. METHODS: An institutional review board-approved anonymous survey was distributed electronically to RO residents in postgraduate years 2 to 5 and those in their first postgraduate years. Questions were included on the type and utility of orientation materials received by residents before and upon entering RO residency. RESULTS: Responses were received from 25.3% of all current and recent residents. Most residents (81.3%) had 2 or 3 months of prior experience rotating in clinical RO. Orientation materials in RO were received by 74.1% of residents before starting residency. An orientation at the start of RO residency was received by 95.4% of RO residents. Orientation length was <1 hour in 2.8%, 1 hour to a half day in 7.8%, more than a half day but <1 full day in 21.8%, >1 full day but <1 week in 45.8%, and >1 week but <1 month in 20.1%. Almost half of RO residents (48.4%) felt that an RO orientation was essential, but only 11.3% of residents felt that their orientation programs were essential. A statistically significant Spearman's correlation was observed between programs with longer orientation and increased helpfulness of orientation (rho = 0.26, P = .008). Residents with more components in their onsite orientations felt that their orientations were more helpful (rho = 0.407, P < .001). CONCLUSIONS: Radiation oncology residents could benefit from a more comprehensive orientation, including a broader array of materials sent to incoming residents for their review before starting residency and a more extensive onsite orientation. PMID- 22051464 TI - Safety in radiation oncology: the role of international initiatives by the International Atomic Energy Agency. AB - The International Atomic Energy Agency (IAEA) has a wide range of initiatives that address the issue of safety. Quality assurance initiatives and comprehensive audits of radiotherapy services, such as the Quality Assurance Team for Radiation Oncology, are available through the IAEA. Furthermore, the experience of the IAEA in thermoluminescence dosimetric audits has been transferred to the national level in various countries and has contributed to improvements in the quality and safety of radiotherapy. The IAEA is also involved in the development of a safety reporting and analysis system (Safety in Radiation Oncology). In addition, IAEA publications describe and analyze factors contributing to safety-related incidents around the world. The lack of sufficient trained, qualified staff members is addressed through IAEA programs. Initiatives include national, regional, and interregional technical cooperation projects, educational workshops, and fellowship training for radiation oncology professionals, as well as technical assistance in developing and initiating local radiation therapy, safety education, and training programs. The agency is also active in developing staffing guidelines and encourages advanced planning at a national level, aided by information collection systems such as the Directory of Radiotherapy Centers and technical cooperation project personnel planning, to prevent shortages of staff. The IAEA also promotes the safe procurement of equipment for radiation therapy centers within a comprehensive technical cooperation program that includes clinical, medical physics, and radiation safety aspects and review of local infrastructure (room layout, shielding, utilities, and radiation safety), the availability of qualified staff members (radiation oncologists, medical physicists, and radiation technologists and therapists), as well as relevant imaging, treatment planning, dosimetry, and quality control items. The IAEA has taken the lead in developing a comprehensive program that addresses all of these areas of concern and is actively contributing to the national and international efforts to make radiation therapy safer in all settings, including resource limited settings. PMID- 22051465 TI - Diagnostic reference levels from the ACR CT Accreditation Program. AB - PURPOSE: The aim of this study was to assess the distribution of CT dose index (CTDI) values reported by sites undergoing ACR CT accreditation between 2002 and 2004. METHODS: Weighted CTDI (CTDI(w)) values were measured and reported by sites applying for ACR CT accreditation, and the percentage of scanners with values above the 2002 ACR diagnostic reference levels (DRLs) was determined. Acquisition parameters for a site's adult head, adult abdominal, and pediatric abdominal examinations were used to calculate volume CTDI (CTDI(vol)), and the average and standard deviation were calculated by year. Histogram analysis was performed to determine 75th and 90th percentiles of CTDI(vol). RESULTS: Between September 2002 and December 2004, 829 scanners underwent the accreditation process. Volume CTDI values (average +/- SD) for 2002, 2003, 2004, and 2002 to 2004, respectively, were 66.7 +/- 23.5, 58.5 +/- 17.5, 55.8 +/- 15.7, and 59.1 +/- 18.6 mGy for adult head examinations; 18.7 +/- 8.0, 19.2 +/- 8.6, 17.0 +/- 7.6, and 18.4 +/- 8.3 for adult abdominal examinations; and 17.2 +/- 9.7, 15.9 +/- 8.6, 14.0 +/- 7.0, and 15.5 +/- 8.4 for pediatric abdominal examinations. For 2004 data, 23.8%, 2.3%, and 6.9% of sites reported doses above the 2002 CTDI(w) reference levels, compared with 49.6%, 4.7%, and 15% for 2002 data for adult head, adult abdominal, and pediatric abdominal examinations, respectively. Seventy-fifth percentiles of CTDI(vol) were 76.8 mGy (adult head, 2002 only), 22.2 mGy (adult abdominal), and 20.0 mGy (pediatric abdominal). CONCLUSIONS: From 2002 to 2004, average CTDI(vol) values decreased by 10.9, 1.7, and 3.2 mGy for adult head, adult abdominal, and pediatric abdominal examinations. Effective January 1, 2008, the ACR program implemented United States-specific diagnostic reference levels of 75, 25, and 20 mGy, respectively, for the CTDI(vol) of routine adult head, adult abdominal, and pediatric abdominal CT scans. PMID- 22051466 TI - Impact of ABR changes on pediatric radiology residency training. AB - PURPOSE: The aim of this study was to assess the impact of new ABR changes on pediatric radiology residency training in terms of the number, timing, availability, and funding of pediatric radiology rotations. METHODS: Participants were selected by using the ACGME's list of accredited American radiology residency programs, and data were collected via a survey. Program directors or persons designated by the program directors filled out the surveys. RESULTS: Of 186 programs, 84 (45%) responded. Three months of pediatric radiology were required in 61.0% of programs, with most having their residents complete one pediatric rotation during postgraduate years 2, 3, and 4. In 46% of training programs, pediatric radiology rotations were completed at the home institution. Seven percent of the programs plan to decrease the number of required pediatric rotations, while 75% plan no changes. Additional rotations in areas of interest are planned for 82% of programs. Only 54% could provide additional rotations in all 10 subspecialties, and 57% indicated that it was "very unlikely" or "impossible" that residents could acquire >=12 months in a single area. Pediatric radiology is among the top 3 most frequent subspecialty areas that cannot be accommodated, along with obstetric and gynecologic (women's) and cardiac imaging. Funding limitations for pediatric rotations were not considered a barrier at 51% of programs. CONCLUSIONS: Seven percent of residency programs plan to cut back the overall number of pediatric radiology core rotations and move them to earlier in training (20%). Although 82% of programs said that they plan to provide more time in areas of interest, 57% said that it is very unlikely or impossible that residents could accumulate >=12 months in an area of interest. It is possible that funding may limit access to additional pediatric rotations in up to 44% of programs. Seventeen of the programs did not know how their institution funded pediatric radiology rotations. PMID- 22051467 TI - If you starve them, will they still come? Do complementary food provisions affect faculty meeting attendance in academic radiology? PMID- 22051468 TI - Two-day workshop on incident reporting, analysis, and learning: defining the structure. PMID- 22051469 TI - Resident and fellow state chapters: providing impact from the local level. PMID- 22051470 TI - Helen C. Redman. PMID- 22051472 TI - Adapting to the new realities of radiology resident education. PMID- 22051474 TI - Concerns about the new logo! PMID- 22051475 TI - Third molars. PMID- 22051476 TI - Clarification of a historical fact. PMID- 22051478 TI - When the tail wags the dog. PMID- 22051480 TI - Three-dimensional analysis of the airway with cone-beam computed tomography. AB - INTRODUCTION: In this study, using a cone-beam computed tomography system, we evaluated the airways of 30 adults. METHODS: The shapes of the 3-dimensional volume of the airway were analyzed and compared among the subjects by using surface superimposition software techniques. RESULTS: The airway had the greatest variability in the hypopharynx, in the region below the epiglottis, and above the vocal folds. Moderate variation was apparent at the nares, behind the soft palate, and at the base of the tongue. Conservation of form was seen at the central portion of the nasal airway surrounding the inferior turbinate. CONCLUSIONS: The potential for comparing the shape of the airway among subjects is possible. PMID- 22051481 TI - Comparison of treatments with the Forsus fatigue resistant device in relation to skeletal maturity: a cephalometric and magnetic resonance imaging study. AB - INTRODUCTION: The aim of this study was to compare the dentoskeletal changes and alterations of mandibular condyle-disc-fossa relationships in subjects at the peak and the end of the pubertal growth period treated with the Forsus fatigue resistant device (3M Unitek, Monrovia, Calif). METHODS: The sample consisted of 29 subjects with Class II Division 1 malocclusions who were classified according to their hand-wrist radiographs. Fifteen patients were at or just before the peak phase of pubertal growth (peak pubertal group). Fourteen patients were near the end of the pubertal growth period (late pubertal group). The study was conducted by using lateral cephalometric radiographs and magnetic resonance images obtained at the beginning and at the end of the application of the Forsus fatigue resistant device. The treatment period was 9 months. RESULTS: The Wilcoxon signed rank test was used to evaluate differences within groups. The changes observed in both groups were compared by using the Mann-Whitney U test. There were statistically significant group differences in mandibular length and ramus length, with significant increases of these parameters in the peak pubertal group (P <0.05). No significant differences were observed between the groups concerning dental parameters (P >0.05), with the exception of mandibular molar vertical movements, which were significantly greater in the peak pubertal group (P <0.05). Analysis of the magnetic resonance images showed no positional changes of the mandibular condyle in relation to the glenoid fossa in either group (P >0.05). Although the articular disc was positioned more anteriorly in the peak pubertal group compared with its pretreatment position (P <0.05), the position of the disc was still within the physiologic range. No significant intergroup difference was observed for disc-condyle relationship (P >0.05). CONCLUSIONS: The Forsus fatigue resistant device did not appear to cause significant increases in mandibular dimensions in subjects in late puberty. According to the magnetic resonance image findings, Forsus treatment is not a risk factor for the development of temporomandibular dysfunction in subjects with no signs and clinical symptoms of dysfunction. PMID- 22051482 TI - Development of a prediction equation for the mixed dentition in a Pakistani sample. AB - INTRODUCTION: Regression equations are widely used for mixed dentition analysis. However, estimations from these equations can vary in different population groups. The aim of this study was to produce simple linear equations and tables for Pakistani children. METHODS: Two hundred subjects of Pakistani descent who met our criteria (ages, 13-15 years; 100 boys, 100 girls) were selected from local schools. The mesiodistal widths of all mandibular permanent incisors, canines, and premolars were measured and analyzed by using paired t tests. The results were also compared with predicted values from the Moyers and the Tanaka and Johnston methods. Correlation and linear regression analyses were performed between the predicted and actual tooth sizes for Pakistani children, and standard regression equations were developed. RESULTS: No significant differences were observed for measured canine and premolar antimeres and sex. Significant and high positive correlations were found between the mandibular incisors and the combined mesiodistal widths of the canines and premolars for the maxillary (r = 0.65; P <0.001) and mandibular (r = 0.59; P <0.001) segments. CONCLUSIONS: The equations and charts commonly used for North American children (75th percentile) did not accurately predict for our sample. The regression equations and tables developed in this study can be used for orthodontic treatment planning for children in Pakistan. PMID- 22051483 TI - Nasal cavity volume changes after rapid maxillary expansion in adolescents evaluated with 3-dimensional simulation and modeling programs. AB - INTRODUCTION: The purpose of this study was to evaluate the effects of rapid maxillary expansion on nasal cavity volume by using 3-dimensional simulation and modeling programs. METHODS: The study group consisted of 15 patients (9 boys, 6 girls; mean age, 13.86 years) with maxillary constriction. Computed tomography scans were obtained before treatment and 6 months after the end of expansion. All computed tomography data were transferred to a computer, and the nasal cavity and maxillary teeth were segmented by using the Mimics and Simplant Ortho software programs (both, Materialise, Leuven, Belgium). Paired samples t tests were used to compare pretreatment and posttreatment nasal cavity volumes and maxillary areas. Data analysis was performed by using the software program SPSS for Windows (version 15.00; SPSS, Chicago, Ill). RESULTS: Rapid maxillary expansion treatment induced significant increases in nasal cavity volume (P <= 0.001) and maxillary transverse dimensions (P <= 0.001). CONCLUSIONS: Both anterior-to-posterior and coronal-to-cranial expansions were observed after rapid maxillary expansion treatment, with the direction of expansion most likely affected by resistance from the cranial bones. PMID- 22051484 TI - Nasal cavity size, airway resistance, and subjective sensation after surgically assisted rapid maxillary expansion: a prospective longitudinal study. AB - INTRODUCTION: The aims of this study were to measure changes in nasal minimum cross-sectional area and nasal airway resistance after surgically assisted rapid maxillary expansion and to explore a possible correlation with the subjective sensation of nasal obstruction. METHODS: Minimum cross-sectional area and nasal airway resistance were measured in 39 consecutive patients treated with surgically assisted rapid maxillary expansion. Subjective nasal obstruction was assessed by a questionnaire at pretreatment and at 3 and 18 months postoperatively. RESULTS: Subjective nasal obstruction had improved significantly by 3 months postoperatively. Minimum cross-sectional area increased and nasal airway resistance decreased. No correlations were found. In subjects with pretreatment subjective nasal obstruction and initially narrow anterior minimum cross-sectional area, there was a significant correlation between a moderate increase in anterior minimum cross-sectional area and improvement in perceived nasal obstruction. Eighteen months postoperatively, no changes were found from pretreatment values for subjective nasal obstruction, minimal cross-sectional area, or nasal airway resistance, and there were no correlations. Subjects with a sensation of nasal obstruction at treatment start reported a lasting significant subjective improvement. CONCLUSIONS: The postoperative effects of surgically assisted rapid maxillary expansion did not persist in the long term. No correlation was found between objective and subjective findings. Subjects with pretreatment nasal obstruction, however, reported a lasting sensation of improved nasal function after surgically assisted rapid maxillary expansion. PMID- 22051485 TI - On the relevance of "ideal" occlusion concepts for incisor inclination target definition. AB - INTRODUCTION: The concept of "ideal" occlusion in harmony with craniofacial structures is often proposed as an ultimate goal of orthodontic treatment. The aim of this study was to assess the impact of slight variations in posterior occlusion and the history of straight-wire orthodontic treatment on the predictability of incisor inclination and third-order angles. METHODS: Axial incisor inclinations, third-order angles, and craniofacial relationships were assessed on lateral headfilms and corresponding dental casts of 75 healthy white subjects, 16 to 26 years old, selected by the general inclusion criterion of a good interincisal relationship. Four groups were formed: group A (n = 17), Angle Class I occlusion subjects with no orthodontic treatment; group B (n = 20), Angle Class I occlusion subjects treated with standardized straight-wire orthodontics; group C (n = 20), up to a half-cusp distal occlusion after straight-wire treatment; and group D (n = 18), up to a half-cusp distal occlusion and no orthodontic treatment. Regression analysis was used to insert predictor angles into selected regression equations of the subjects with "ideal" occlusion, and the absolute differences between predicted and observed response angles were determined. RESULTS: Small differences in incisor inclination were found between subjects with "ideal" occlusion and those who slightly deviated from "ideal" with a mild occlusion of the Angle Class II category. Posterior occlusion was not relevant to the validity of the vast majority of predictor-response pairs. Straight-wire treatment produced incisor inclination that was slightly protruded compared with subjects who had good natural occlusion. CONCLUSIONS: The "ideal" posterior occlusion concepts as a general orthodontic treatment goal should be reconsidered. PMID- 22051486 TI - MI Paste Plus to prevent demineralization in orthodontic patients: a prospective randomized controlled trial. AB - INTRODUCTION: Enamel demineralization is a problem in orthodontics. Fluoride is partially effective in addressing this problem, but additional treatment options are needed. The objective of this prospective randomized controlled trial was to determine the effectiveness of a new product, MI Paste Plus (GC America, Alsip, Ill), in the prevention or reduction of white spot lesions in orthodontic patients. METHODS: Sixty patients who were undergoing routine orthodontic treatment were recruited for this prospective randomized clinical trial. A double blind method of randomization was used to determine whether each patient received the MI Paste Plus or a placebo paste (Tom's of Maine, Salisbury, United Kingdom). Each patient was asked to administer the paste by using a fluoride tray for a minimum of 3 to 5 minutes each day at night after brushing. Photographic records obtained in a light-controlled environment were used to record the presence or absence of white spot lesions in both groups. The enamel decalcification index was used to determine the number of white spot lesions per surface at each time interval. Patients were followed at 4-week intervals for 3 months. A scoring system from 0 to 6 was used to determine the level of caries or cavitations. This system was also used for each tooth at each time interval. RESULTS: Fifty patients (26 using MI Paste Plus, 24 using the placebo paste) completed the study. The enamel decalcification index scores for all surfaces were 271 and 135 at the start of treatment and 126 and 258 at the end of treatment for the MI Paste Plus and placebo paste groups, respectively. The enamel decalcification index scores in the MI Paste Plus group reduced by 53.5%, whereas the placebo group increased by 91.1% during the study period. A 3-way analysis of variance (ANOVA) was done for the average enamel decalcification index scores. The surface type, the product/time interactions, and the product/surface interactions of the mean enamel decalcification index scores were significant (P <0.05). CONCLUSIONS: MI Paste Plus helped prevent the development of new white spot lesions during orthodontic treatment and decreased the number of white spot lesions already present. The placebo paste had no preventive action on white spot development during orthodontic treatment; the number of lesions actually increased. MI Paste Plus reduced white spots on the gingival surfaces; the placebo paste had the opposite effect. The incisal surface effect on the mean enamel decalcification index scores over time and between products was highly significant. The incisal enamel decalcification index scores were consistently higher than those for the other surfaces (mesial, distal, and gingival). PMID- 22051487 TI - Malocclusions and perceptions of attractiveness, intelligence, and personality, and behavioral intentions. AB - INTRODUCTION: In this study, we explored how others perceive persons with normal occlusion or different malocclusions (open bite, deepbite, underbite, overjet, crowding, and spacing). The objectives were to investigate (1) how occlusion affects others' perceptions of attractiveness, intelligence, and personality, and their desire to interact in personal and professional settings, and (2) whether these assessments are affected by the target person's sex or the respondent's characteristics. METHODS: Survey data were collected from 889 patients or accompanying adults (46% male, 54% female; age range, 18-90 years) who evaluated target photos that had been manipulated to display either a normal occlusion or 1 of 6 malocclusions. RESULTS: The ratings of attractiveness, intelligence, conscientiousness, agreeableness, and extraversion differed significantly depending on the occlusion status depicted. Persons with normal occlusion were rated as most attractive, intelligent, agreeable, and extraverted, whereas persons with an underbite were rated as least attractive, intelligent, and extraverted. Female targets were rated more positively than male targets. Younger respondents and more educated respondents were more critical in their evaluations than were older and less educated respondents. CONCLUSIONS: Occlusion status affects a person's perceptions comprehensively. Subjects with normal occlusion were rated the most positively. PMID- 22051488 TI - Discriminant factor analysis of dental arch dimensions with 3-dimensional virtual models. AB - INTRODUCTION: The form and the size of a dental arch are products of the configuration and the naturally established balance of the jaw, alveolar bone, and muscles. We investigated which arch dimensions mostly discriminate particular dentoalveolar classes and sexes. METHODS: Plaster dental casts were collected from 137 white adolescent subjects (71 girls, 66 boys) aged between 15 and 18 years (mean, 16.0 +/- 1.2 years) with Class I (43 subjects: 24 girls, 19 boys), Class II (50 subjects: 28 girls, 22 boys), and Class III (44 subjects: 19 girls, 25 boys) malocclusions. Casts were scanned with the ATOS II SO (small objects) scanner (GOM mbH, Braunschweig, Germany) and measured with ATOS Viewer software (version 6.0.2; GOM mbH). RESULTS: The major discriminating factors of the particular dentoalveolar classes are the mandibular canine width/depth ratio and the maxillary molar width/depth ratio, which explain 82.8% of the total variability (P <0.001). Class III subjects with the widest and shallowest frontal segment of the mandibular arch and the posterior segment of maxillary arch are clearly distinguished from Class II subjects whose abovementioned segments are the deepest and narrowest. Class I subjects are more similar to Class II than to Class III subjects. The most homogenous are Class III subjects, with 61.1% of them correctly classified, followed by Class II (57.8%) and Class I (52.4%). Sex differences are significant in linear measurements, but not in ratios. CONCLUSIONS: Variability of dental arch dimensions and forms is a common characteristic of all dentoalveolar classes. Maxillary arch form is more distinguishing in the posterior segment, and mandibular arch form is more distinguishing in the anterior segment. Class III patients have the most detectable arch form, and Class I the least detectable arch form. PMID- 22051489 TI - Efficacy of 2 finishing protocols in the quality of orthodontic treatment outcome. AB - INTRODUCTION: The objectives of this prospective clinical study were to evaluate the quality of treatment outcomes achieved with a complex orthodontic finishing protocol involving serpentine wires and a tooth positioner, and to compare it with the outcomes of a standard finishing protocol involving archwire bends used to detail the occlusion near the end of active treatment. METHODS: The complex finishing protocol sample consisted of 34 consecutively treated patients; 1 week before debonding, their molar bands were removed, and serpentine wires were placed; this was followed by active wear of a tooth positioner for up to 1 month after debonding. The standard finishing protocol group consisted of 34 patients; their dental arches were detailed with archwire bends and vertical elastics. The objective grading system of the American Board of Orthodontics was used to quantify the quality of the finish at each time point. The Wilcoxon signed rank test was used to compare changes in the complex finishing protocol; the Mann Whitney U test was used to compare changes between groups. RESULTS: The complex finishing protocol group experienced a clinically significant improvement in objective grading system scores after treatment with the positioner. Mild improvement in posterior space closure was noted after molar band removal, but no improvement in the occlusion was observed after placement of the serpentine wires. Patients managed with the complex finishing protocol also had a lower objective grading system score (14.7) at the end of active treatment than did patients undergoing the standard finishing protocol (23.0). CONCLUSIONS: Tooth positioners caused a clinically significant improvement in interocclusal contacts, interproximal contacts, and net objective grading system score; mild improvement in posterior band space was noted after molar band removal 1 week before debond. PMID- 22051490 TI - Evaluation of enamel surfaces after bracket debonding: an in-vivo study with scanning electron microscopy. AB - INTRODUCTION: The purposes of this in-vivo study were to compare the modes of failure of uncoated and adhesive precoated metal brackets by using the adhesive remnant index, and to assess the quality of the enamel surface after cleanup by using the enamel damage index. METHODS: Twelve Victory brackets (group A) and 12 Victory adhesive precoated brackets (group B) (both, 3M Unitek, Monrovia, Calif) were bonded onto the maxillary second premolars of 12 volunteers. The uncoated brackets were bonded with Transbond XT adhesive resin (3M Unitek). Replicas of the teeth were made before bonding (T0), after bracket removal (T1), and after cleanup (T2). Scanning electron microscope images of all labial enamel surfaces were taken at T0, T1, and T2, and these were evaluated according to the adhesive remnant index and the enamel damage index. RESULTS: Evaluation of the adhesive remnant index scores with the chi-square test showed no statistically significant difference between the groups. Evaluation of the enamel damage index grades with the sign test for paired samples showed a statistically significant difference (P <0.01) between T0 and T2. CONCLUSIONS: Uncoated and precoated brackets exhibited similar debonding patterns. Additionally, the debonding method tested in this study did not restore the original enamel surface, although there was no clinically relevant enamel damage. PMID- 22051491 TI - Orthodontic-orthognathic surgical treatment in a patient with Class II subdivision malocclusion: occlusal plane alteration. AB - Despite the different orthodontic treatment options for patients with Class II subdivision malocclusions, the involvement of the skeletal structures is significant. It is desirable to combine orthodontic and surgical treatment to achieve a stable and better esthetic result, as illustrated in this case report. The occlusal plane was canted to the right as a part of the patient's facial asymmetry. Consequently, a 3-mm differential impaction of the maxilla on the left side allowed occlusal plane leveling. Mandibular rotation with advancement on the right side corrected the right Class II malocclusion. The successful attainment of the treatment goals was accomplished through teamwork and integration between the orthodontist and the maxillofacial surgeon. PMID- 22051493 TI - Corticotomy-assisted decompensation for augmentation of the mandibular anterior ridge. AB - INTRODUCTION: This article introduces a technique combining corticotomy and orthodontic forces, or accelerated osteogenic orthodontics, for use in patients with a Class III occlusion and a thin alveolus who will undergo orthognathic surgery. METHODS: Two adults with Class III malocclusion undergoing anterior decompensation for mandibular setback surgery were selected. The first patient was treated with accelerated osteogenic orthodontics and conventional decompensation. The second patient was treated with accelerated osteogenic orthodontics and decompensation with a temporary skeletal anchorage device in concert with guided tissue regeneration. Decortication of bone was performed to the mandibular teeth with a low-speed round bur and piezosurgery. After hemostasis, bone graft material was placed into the decorticated area. In the severely thin alveolar ridge, a rigid scaffold was applied for immobilization of graft material. After approximation of the flap, an immediate orthodontic force was applied to the teeth to initiate rapid tooth movement. RESULTS: Rapid tooth movement into predetermined positions for orthognathic surgery was accomplished in all mandibular anterior teeth. Preoperative 3-dimensional imaging showed dehiscences on the facial aspects of the mandibular anterior teeth. Postoperative imaging demonstrated coverage of the denuded roots with radiodense material. CONCLUSIONS: The accelerated osteogenic orthodontic technique is a safe and effective treatment option for mandibular anterior decompensation treatment of these patients. When combined with a temporary skeletal anchorage device and bone augmentation, this technique facilitated the decompression of the mandibular anterior teeth in severely compromised dentitions. PMID- 22051492 TI - Orthodontic treatment in a patient with sickle cell anemia. AB - Sickle cell anemia is a common hereditary hematologic disease. It affects many systems and tissues in the body, including the mouth. Delayed tooth eruption, an uncommon degree of periodontitis, alterations in the cells of the tongue surface, hypomaturation and hypomineralization in enamel and dentin, pulp calcifications, hypercementosis, and bone alterations resulting in maxillary protrusion and formation of a thick trabecular pattern are some oral manifestations of the disease. The aim of this study was to report the orthodontic treatment of a patient with sickle cell anemia. Treatment consisted of correcting a Class II dental and skeletal pattern with an extraoral appliance combined with a fixed orthodontic appliance. From the orthodontic point of view, the results were satisfactory: the occlusion was normalized, and the patient's health was maintained throughout the entire treatment period. PMID- 22051494 TI - Facial lipodystrophy in an HIV-positive patient using an orthodontic appliance. AB - The aim of this article was to relate the clinical case of an HIV-positive orthodontic patient who reported that her cheeks had been hurting since treatment began. We started with the data collected in anamnesis and by contact with the patient's physician, and a diagnosis of facial lipodystrophy as a result of the use of retroviral drugs was reached. The patient was referred to a dermatologist for treatment of the facial lipodystrophy. PMID- 22051495 TI - Accuracy and reliability of buccal bone height and thickness measurements from cone-beam computed tomography imaging. AB - INTRODUCTION: Cone-beam computed tomography (CBCT) imaging has broadened opportunities for examining morphologic aspects of the craniofacial complex, including alveolar bone, but limitations of the technology have yet to be defined. Through the use of comparisons with direct measurements, the purpose of this study was to investigate the accuracy and reliability of buccal alveolar bone height and thickness measurements derived from CBCT images. METHODS: Twelve embalmed cadaver heads (5 female, 7 male; mean age: 77 years) were scanned with an i-CAT 17-19 unit (Imaging Sciences International, Hatfield, Pa) at 0.3 mm voxel size. Buccal alveolar bone height and thickness measurements of 65 teeth were made in standardized radiographic slices and compared with direct measurements made by dissection. All measurements were repeated 3 times by 2 independent raters and examined for intrarater and interrater reliability. Measurement means were compared with 2-tailed t tests. Agreement between direct and CBCT measurements was assessed by concordance correlation coefficients, Pearson correlation coefficients, and Bland-Altman plots. RESULTS: Intrarater reliability was high as were interrater correlations for all measurements (>=0.97) except CBCT buccal bone thickness (0.90). CBCT measurements did not differ significantly from direct measurements, and there was no pattern of underestimation or overestimation. The mean absolute differences were 0.30 mm in buccal bone height and 0.13 mm in buccal bone thickness with 95% limits of agreement of -0.77 to 0.81 mm, and -0.32 to 0.38 mm, respectively. Agreement between the 2 methods was higher for the measurements of buccal bone height than buccal bone thickness, as demonstrated by concordance correlation coefficients of 0.98 and 0.86, respectively. CONCLUSIONS: For the protocol used in this study, CBCT can be used to quantitatively assess buccal bone height and buccal bone thickness with high precision and accuracy. Comparing the 2 sets of CBCT measurements, buccal bone height had greater reliability and agreement with direct measurements than did the buccal bone thickness measurements. PMID- 22051496 TI - Litigation and legislation. Don't bug me. PMID- 22051497 TI - Randomization. Part 1: sequence generation. PMID- 22051498 TI - Physical properties of root cementum: part 20. Effect of fluoride on orthodontically induced root resorption with light and heavy orthodontic forces for 4 weeks: a microcomputed tomography study. AB - INTRODUCTION: The major side effect of orthodontic treatment is orthodontically induced inflammatory root resorption. Fluoride was previously shown to reduce the volume of the root resorption craters in rats. However, the effect of fluoride on orthodontically induced inflammatory root resorption in humans has not yet been investigated. The aim of this study was to investigate the effect of high and low amounts of fluoride intake from birth on orthodontically induced inflammatory root resorption under light (25 g) and heavy (225 g) force applications. METHODS: Forty-eight patients who required maxillary premolar extractions as part of their orthodontic treatment were selected from 2 cities in Turkey with high and low fluoride concentrations in the public water of >= 2 and <= 0.05 ppm, respectively. The patients were randomly separated into 4 groups of 12 each: group 1, high fluoride intake and heavy force; group 2, low fluoride intake and heavy force; group 3, high fluoride intake and light force; and group 4, low fluoride intake and light force. Light or heavy buccal tipping orthodontic forces were applied on the maxillary first premolars for 28 days. At day 28, the teeth were extracted, and the samples were analyzed with microcomputed tomography. RESULTS: Fluoride reduced the volume of root resorption craters in all groups; however, this effect was significantly different with high force application (P = 0.015). It was also found that light forces caused less root resorption than heavy forces. There was no statistical difference in the amount of root resorption observed on root surfaces (buccal, lingual, mesial, and distal) in all groups. However, the middle third of the roots showed the least root resorption. With high fluoride intake and heavy force application, less root resorption was found in all root surfaces and root thirds. CONCLUSIONS: Fluoride may reduce the volume of root resorption craters. This effect is significant with heavy force applications (P <0.05). The cervical and apical thirds of the root showed significantly greater root resorption after the application of buccal tipping force for 4 weeks. PMID- 22051499 TI - How does the rate of dentoalveolar distraction affect the bone regenerate produced? AB - INTRODUCTION: This experimental study was designed to evaluate how the rate of dentoalveolar distraction into a bony defect affects bone quality and quantity. METHODS: Using 6 adult foxhound dogs and a randomized split-mouth design, we evaluated the differences between regenerate bone produced by distracting segments of bone containing the second premolars at either 1 or 2 mm per day for 5 days, followed by a 6-week consolidation period. Microcomputed tomography was used to evaluate bone density, percent bone volume, trabecular number, trabecular separation, and trabecular thickness. RESULTS: The lingual aspect of the regenerate exhibited more bone than did the buccal aspect, and all but one of the 12 specimens showed less than 1 mm of vertical bone deficiency in the regenerate area. No differences were found between the 1-mm per day and the 2-mm per day rates for bone density, percent bone volume, trabecular number, trabecular separation, and trabecular thickness. With the exception of trabecular separation on the 2-mm per day side (P = 0.030), there were no statistically significant differences between the mesial, middle, and distal segments of the regenerate. Compared with control bone, the regenerate bone was less dense, and had less bone volume, a higher trabecular number, and approximately half the trabecular thickness. CONCLUSIONS: Bone regenerate produced by rates of 1 and 2 mm per day of dentoalveolar distraction was similar in quality and quantity. Although less mature, the size and shape of the regenerate bone produced by rapid dentoalveolar distraction was comparable with the control bone. PMID- 22051500 TI - Effects of modified and conventional facemask therapies with expansion on dynamic measurement of natural head position in Class III patients. AB - INTRODUCTION: The aim of this prospective clinical trial was to assess the effects of varying force directions on the dynamic measurement of natural head position and orofacial airway dimensions of Class III patients during maxillary orthopedic protraction compared with an untreated control group. METHODS: The conventional facemask group comprised 15 patients (8 girls, 7 boys; mean age, 9.6 +/- 1.3 years), the modified facemask group comprised 15 patients (7 girls, 8 boys; mean age, 9.5 +/- 1.5 years), and the control group comprised 15 subjects (7 girls, 8 boys; mean age, 9.8 +/- 1.6 years). Natural head position measurements and cephalometric records were obtained from all subjects before and after treatment or the control period (approximately 1 year). An inclinometer and a portable data logger were used to collect the dynamic natural head position data. For statistical comparisons, paired samples t tests, analysis of variance (ANOVA), and post-hoc Tukey tests were used at the P <0.05 level. RESULTS: Both treatment groups showed statistically significant changes in the sagittal (pitch) measurements of natural head position and upper pharynx, aerial, and total area of airway measurements during the treatment period. In the control group, the only statistically significant change was an increased upper pharynx measurement (P = 0.020). According to the intergroup comparisons, statistically significant natural head position differences were found in the conventional (6.4 degrees flexion) and the modified (5.7 degrees flexion) facemask groups when compared with the controls. The modified facemask group also showed significant changes in aerial (P = 0.003) and total (P <0.001) areas of the airway measurements compared with the control group. No statistically significant differences were observed between the 2 treatment groups. CONCLUSIONS: These findings suggest that modified and conventional facemask therapy with expansion have significant cranial flexion effects on the dynamic measurements of natural head position. Additionally, the modified facemask procedure showed significant effects on the orofacial airway dimensions compared with the initial values and the values of the untreated controls. PMID- 22051501 TI - Maxillary posterior intrusion mechanics with mini-implant anchorage evaluated with the finite element method. AB - INTRODUCTION: The goal of this study was to evaluate the effects of 3 maxillary posterior intrusion mechanics with mini-implant anchorage by using the finite element method. METHODS: Finite element models were generated by assembling the images obtained by computed tomography and a laser surface scanner. For each posterior dental segment, a 300-g force was applied and distributed to the mini implants in proportion to their calculated root surface areas. RESULTS: The most balanced intrusion and the most uniform stress distribution were obtained by concurrent force applications from the vestibular and palatinal sides. In the models with transpalatal arches and buccal force application, vestibular tipping movement and overall stress values were prominent. In all models, increased stress values were identified at the apical region of the first premolar roots and at the apical region of the first molar mesial root. CONCLUSIONS: The results of this study suggest that the apical region of the first premolar roots and the apical region of the first molar mesial root should be considered to be prone to resorption during posterior intrusion treatment. Posterior intrusion systems with force application from counterbalancing sites lead to a more uniform stress distribution and balanced intrusion than the mechanics with a transpalatal arch. For a balanced intrusion, root surface areas should be considered when determining the appropriate forces. PMID- 22051502 TI - Real-time cell analysis of the cytotoxicity of the components of orthodontic acrylic materials on gingival fibroblasts. AB - INTRODUCTION: The aim of this study was to evaluate the cytotoxicity of 3 orthodontic acrylic materials and 2 manipulation methods. METHODS: The orthodontic acrylic materials Orthocryl EQ (Dentaurum, Ispringen, Germany), Orthoplast (Vertex Dental, Zeist, The Netherlands), and O-80 (Imicryl, Konya, Turkey) were prepared with 2 polymerization methods (doughing and spray on). Totally, 60 cylinders (5 * 2 mm), fabricated by using a different acrylic and method, were divided into 6 groups. Gingival fibroblasts were isolated from gingival connective tissue of systemically healthy subjects. Materials were incubated in Dulbecco's modified eagle's medium culture medium (Biological Industries, Beit Haemek, Israel) for 72 hours according to ISO 10993-5 standards (surface area to volume ratio of the specimen to cell-culture medium: 3 cm(2)/mL). Gingival fibroblasts were maintained with Dulbecco's modified eagle medium containing 10% fetal bovine serum. A real-time cell analyzer (RT-CES, xCELLigence; Roche Applied Science, Mannheim, Germany, and ACEA Biosciences, San Diego, Calif) was used to evaluate cell survival. After seeding 200 MUL of the cell suspensions into the wells (20,000 cells/well) of the E-plate 96, gingival fibroblasts were treated with bioactive components released by the acrylic materials (1/1 and 1/2 dilutions) and monitored every 15 minutes for 121 hours. For the proliferation experiments, the statistical analyses used were 1-way analysis of variance (ANOVA) and Tukey-Kramer multiple comparisons tests. RESULTS: There was no significant difference between the cell indexes of the control and study groups for the 1/1 and 1/2 dilutions at 21 and 32 hours. When evaluated at 68 hours, all 1/2 dilutions of acrylic materials showed statistically insignificant differences (P >0.05) except for Orthoplast (P <0.05). But all acrylic materials were different from the control group in the 1/1 dilutions (P <0.001). At 121 hours, all test groups were significantly different from the untreated control group (P <0.001). CONCLUSIONS: The results indicate that the long cycle increased the cytotoxicity of the tested materials, and there was no significant difference between the spray-on and doughing methods on cytotoxicity. PMID- 22051503 TI - Comparison between the automated Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 2.0 assay and its version 1 and Nuclisens HIV-1 EasyQ version 2.0 assays when measuring diverse HIV-1 genotypes in China. AB - BACKGROUND: Several commercially available HIV-1 viral load assays based on real time detection technology and automated platforms are available. It is not clear how the diversity of HIV-1 genotypes impacts the ability to consistently detect HIV-1 viral loads. OBJECTIVES: To examine whether the diversity of HIV-1 genotypes impacts the ability of the Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 2.0 (CAP/CTM v2.0), its version 1.0 (CAP/CTM v1.0) and the NucliSens EasyQ HIV-1 version 2.0 (EasyQ v2.0) assays to consistently determine the viral loads. STUDY DESIGN: The three assays were used to measure the viral load in 178 plasma samples with diverse genotypes from treatment-naive patients. RESULTS: CAP/CTM v2.0 showed significant correlation and high agreement with CAP/CTM v1.0 and EasyQ v2.0. CAP/CTM v2.0 showed excellent detection of clade B samples compared with CAP/CTM v1.0 and EasyQ v2.0. However, significant differences were observed when using CAP/CTM v2.0 to test clade BC and AE samples. The HIV-1 load measured by CAP/CTM v2.0 differed by >0.5logIU/ml in 59.52% and 72.62% of clade BC samples, and in 57.14% and 85.71% of clade AE samples, compared with CAP/CTM v1.0 and EasyQ v2.0, respectively. CAP/CTM v2.0 was more precise (13.18%) than EasyQ v2.0 (29.21%), and both assays showed good linearity (R>=0.9926). CONCLUSIONS: The three assays may not deliver consistent results for samples belonging to clades BC and AE. It is strongly suggested that the version of the HIV-1 viral load assay used initially is also used at follow-up. PMID- 22051504 TI - Rash in a neonate. PMID- 22051505 TI - Heart transplantation and cardiac amyloidosis: approach to screening and novel management strategies. AB - Limited data exist regarding screening methods and outcomes for orthotopic heart transplantation (OHT) in cardiac amyloidosis. As a result, uncertainty exists over the best approach to OHT for cardiac amyloidosis and for the timing of critical post-transplant therapies. This article reviews 6 patients who underwent OHT for cardiac amyloidosis at the Stanford University Amyloid Center from 2008 to present. All patients with light-chain amyloidosis received chemotherapy in the interval between OHT and autologous hematopoietic stem cell transplant. Five patients remain alive up to 25 months after OHT, without evidence of recurrent cardiac amyloid deposition. A novel strategy of OHT, followed by light-chain suppressive chemotherapy before autologous hematopoietic stem cell transplant, is feasible for patients with light-chain amyloidosis. PMID- 22051506 TI - Endobronchial valve therapy for pneumothorax as a bridge to lung transplantation. PMID- 22051507 TI - The role of mammalian PPR domain proteins in the regulation of mitochondrial gene expression. AB - Pentatricopeptide repeat (PPR) domain proteins are a large family of RNA-binding proteins that are involved in the maturation and translation of organelle transcripts in eukaryotes. They were first identified in plant organelles and their important role in mammalian mitochondrial gene regulation is now emerging. Mammalian PPR proteins, like their plant counterparts, have diverse roles in mitochondrial transcription, RNA metabolism and translation and consequently are important for mitochondrial function and cell health. Here we discuss the current knowledge about the seven mammalian PPR proteins identified to date and their roles in the regulation of mitochondrial gene expression. Furthermore we discuss the mitochondrial RNA targets of the mammalian PPR proteins and methods to investigate the RNA targets of these mitochondrial RNA-binding proteins. This article is part of a Special Issue entitled: Mitochondrial Gene Expression. PMID- 22051508 TI - Safety and clinical activity of ipilimumab in melanoma patients with brain metastases: retrospective analysis of data from a phase 2 trial. AB - Melanoma has a high propensity to metastasize to the brain, and this is often responsible for treatment failure in patients with advanced disease. Melanoma patients with brain metastases are usually excluded from clinical trials because of their expected survival of approximately 5 months. A growing body of evidence suggests that ipilimumab, a human monoclonal antibody that blocks cytotoxic T lymphocyte antigen-4, has activity against melanoma brain metastases. We conducted a retrospective analysis of data from a phase II study of ipilimumab in advanced melanoma patients. Twelve of 115 patients randomized in the parent trial had stable brain metastases at baseline, as identified by an Independent Review Committee, and were evaluated for efficacy. Two of the 12 patients achieved a partial response and three had stable disease. Both patients with a partial response and one with stable disease were alive at the last follow-up, with survival time of more than 4 years. The median overall survival of the 12 patients was 14 months (range: 2.7-56.4+). An additional four patients with stable brain metastases at baseline were identified by a secondary Independent Review Committee reviewer, and were evaluated for safety. Central nervous system related adverse events of grade 3-4, specifically cerebral edema and convulsion/seizure, occurred in two of 16 patients. Although the present study is limited by the fact that it is a retrospective analysis of a small number of patients, the results provide further evidence for the safety and efficacy of ipilimumab in melanoma patients with stable brain metastases. PMID- 22051509 TI - Evaluation of self-assessed melanoma growth rate in a Mediterranean patient population. PMID- 22051511 TI - Oligomerization propensity and flexibility of yeast frataxin studied by X-ray crystallography and small-angle X-ray scattering. AB - Frataxin is a mitochondrial protein with a central role in iron homeostasis. Defects in frataxin function lead to Friedreich's ataxia, a progressive neurodegenerative disease with childhood onset. The function of frataxin has been shown to be closely associated with its ability to form oligomeric species; however, the factors controlling oligomerization and the types of oligomers present in solution are a matter of debate. Using small-angle X-ray scattering, we found that Co(2+), glycerol, and a single amino acid substitution at the N terminus, Y73A, facilitate oligomerization of yeast frataxin, resulting in a dynamic equilibrium between monomers, dimers, trimers, hexamers, and higher-order oligomers. Using X-ray crystallography, we found that Co(2+) binds inside the channel at the 3-fold axis of the trimer, which suggests that the metal has an oligomer-stabilizing role. The results reveal the types of oligomers present in solution and support our earlier suggestions that the trimer is the main building block of yeast frataxin oligomers. They also indicate that different mechanisms may control oligomer stability and oligomerization in vivo. PMID- 22051513 TI - Influence of histone tails and H4 tail acetylations on nucleosome-nucleosome interactions. AB - Nucleosome-nucleosome interaction plays a fundamental role in chromatin folding and self-association. The cation-induced condensation of nucleosome core particles (NCPs) displays properties similar to those of chromatin fibers, with important contributions from the N-terminal histone tails. We study the self association induced by addition of cations [Mg(2+), Ca(2+), cobalt(III)hexammine(3+), spermidine(3+) and spermine(4)(+)] for NCPs reconstituted with wild-type unmodified histones and with globular tailless histones and for NCPs with the H4 histone tail having lysine (K) acetylations or lysine-to-glutamine mutations at positions K5, K8, K12 and K16. In addition, the histone construct with the single H4K16 acetylation was investigated. Acetylated histones were prepared by a semisynthetic native chemical ligation method. The aggregation behavior of NCPs shows a general cation-dependent behavior similar to that of the self-association of nucleosome arrays. Unlike nucleosome array self association, NCP aggregation is sensitive to position and nature of the H4 tail modification. The tetra-acetylation in the H4 tail significantly weakens the nucleosome-nucleosome interaction, while the H4 K->Q tetra-mutation displays a more modest effect. The single H4K16 acetylation also weakens the self association of NCPs, which reflects the specific role of H4K16 in the nucleosome nucleosome stacking. Tailless NCPs can aggregate in the presence of oligocations, which indicates that attraction also occurs by tail-independent nucleosome nucleosome stacking and DNA-DNA attraction in the presence of cations. The experimental data were compared with the results of coarse-grained computer modeling for NCP solutions with explicit presence of mobile ions. PMID- 22051512 TI - DDX1 is an RNA-dependent ATPase involved in HIV-1 Rev function and virus replication. AB - The human immunodeficiency virus type 1 (HIV-1) Rev protein is essential for the virus because it promotes nuclear export of alternatively processed mRNAs, and Rev is also linked to translation of viral mRNAs and genome encapsidation. Previously, the human DEAD-box helicase DDX1 was suggested to be involved in Rev functions, but this relationship is not well understood. Biochemical studies of DDX1 and its interactions with Rev and model RNA oligonucleotides were carried out to investigate the molecular basis for association of these components. A combination of gel-filtration chromatography and circular dichroism spectroscopy demonstrated that recombinant DDX1 expressed in Escherichia coli is a well behaved folded protein. Binding assays using fluorescently labeled Rev and cell based immunoprecipitation analysis confirmed a specific RNA-independent DDX1-Rev interaction. Additionally, DDX1 was shown to be an RNA-activated ATPase, wherein Rev-bound RNA was equally effective at stimulating ATPase activity as protein free RNA. Gel mobility shift assays further demonstrated that DDX1 forms complexes with Rev-bound RNA. RNA silencing of DDX1 provided strong evidence that DDX1 is required for both Rev activity and HIV production from infected cells. Collectively, these studies demonstrate a clear link between DDX1 and HIV-1 Rev in cell-based assays of HIV-1 production and provide the first demonstration that recombinant DDX1 binds Rev and RNA and has RNA-dependent catalytic activity. PMID- 22051514 TI - A three-dimensional FRET analysis to construct an atomic model of the actin tropomyosin complex on a reconstituted thin filament. AB - Fluorescence resonance energy transfer (FRET) was used to construct an atomic model of the actin-tropomyosin (Tm) complex on a reconstituted thin filament. We generated five single-cysteine mutants in the 146-174 region of rabbit skeletal muscle alpha-Tm. An energy donor probe was attached to a single-cysteine Tm residue, while an energy acceptor probe was located in actin Gln41, actin Cys374, or the actin nucleotide binding site. From these donor-acceptor pairs, FRET efficiencies were determined with and without Ca(2+). Using the atomic coordinates for F-actin and Tm, we searched all possible arrangements for Tm segment 146-174 on F-actin to calculate the FRET efficiency for each donor acceptor pair in each arrangement. By minimizing the squared sum of deviations for the calculated FRET efficiencies from the observed FRET efficiencies, we determined the location of the Tm segment on the F-actin filament. Furthermore, we generated a set of five single-cysteine mutants in each of the four Tm regions 41-69, 83-111, 216-244, and 252-279. Using the same procedures, we determined each segment's location on the F-actin filament. In the best-fit model, Tm runs along actin residues 217-236, which were reported to compose the Tm binding site. Electrostatic, hydrogen-bonding, and hydrophobic interactions are involved in actin and Tm binding. The C-terminal region of Tm was observed to contact actin more closely than did the N-terminal region. Tm contacts more residues on actin without Ca(2+) than with it. Ca(2+)-induced changes on the actin-Tm contact surface strongly affect the F-actin structure, which is important for muscle regulation. PMID- 22051515 TI - Disruption of a long distance regulatory region upstream of SOX9 in isolated disorders of sex development. AB - BACKGROUND: The early gonad is bipotential and can differentiate into either a testis or an ovary. In XY embryos, the SRY gene triggers testicular differentiation and subsequent male development via its action on a single gene, SOX9. The supporting cell lineage of the bipotential gonad will differentiate as testicular Sertoli cells if SOX9 is expressed and conversely will differentiate as ovarian granulosa cells when SOX9 expression is switched off. RESULTS: Through copy number variation mapping this study identified duplications upstream of the SOX9 gene in three families with an isolated 46,XX disorder of sex development (DSD) and an overlapping deletion in one family with two probands with an isolated 46,XY DSD. The region of overlap between these genomic alterations, and previously reported deletions and duplications at the SOX9 locus associated with syndromic and isolated cases of 46,XX and 46,XY DSD, reveal a minimal non-coding 78 kb sex determining region located in a gene desert 517-595 kb upstream of the SOX9 promoter. CONCLUSIONS: These data indicate that a non-coding regulatory region critical for gonadal SOX9 expression and subsequent normal sex development is located far upstream of the SOX9 promoter. Its copy number variations are the genetic basis of isolated 46,XX and 46,XY DSDs of variable severity (ranging from mild to complete sex reversal). It is proposed that this region contains a gonad specific SOX9 transcriptional enhancer(s), the gain or loss of which results in genomic imbalance sufficient to activate or inactivate SOX9 gonadal expression in a tissue specific manner, switch sex determination, and result in isolated DSD. PMID- 22051516 TI - Sex differences in reproductive fitness contribute to preferential maternal transmission of 22q11.2 deletions. AB - BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans. In a minority of patients, the underlying 22q11.2 deletion is found to have been inherited, usually from an affected mother. Serious neuropsychiatric conditions that are commonly associated features of 22q11.2DS could disproportionately affect reproductive success in males. METHODS: This study compared standard measures of reproductive fitness (mean number of liveborn offspring and proportion childless) in 141 Canadian adults with 22q11.2DS (cases) and their 200 unaffected siblings (controls). Multivariate regression models were used to identify phenotypic predictors of fitness in 22q11.2DS. RESULTS: The adults with 22q11.2DS had significantly fewer children than their siblings (p<0.0001, relative fitness=0.28); 85.8% were childless. As expected, younger age (p<0.0001), mental retardation (p=0.0211), and schizophrenia (p=0.0046) were significant negative predictors of reproductive fitness in 22q11.2DS; however, serious congenital heart disease was not. Female sex emerged as a significant positive predictor of fitness independent of the major neuropsychiatric phenotypes (p=0.0082). Post-hoc analyses corroborated these sex differences. Notably, fitness in women with 22q11.2DS with neither mental retardation nor schizophrenia was not significantly different from that of unaffected female siblings. CONCLUSIONS: There is a strong negative selective pressure against 22q11.2 deletions. This appears to be primarily mediated by the severity of the neuropsychiatric phenotype and an independent sexual selection effect. The latter also contributes to the observed excess of transmitting mothers. These results may have implications both for the evolutionary biology of this structural rearrangement and for genetic counselling and reproductive services for adolescents and adults with 22q11.2DS. PMID- 22051517 TI - Exposure to keyboard/mouse use = keystrokes + mouse clicks + POSTURE: a missing variable that cannot be overstated. PMID- 22051518 TI - Is carpal tunnel syndrome overdiagnosed? PMID- 22051519 TI - Dutch health minister is quizzed about "intensive" contact with tobacco industry. PMID- 22051520 TI - Obama takes action on drugs shortages. PMID- 22051521 TI - Lack of clarity and high expectations could lead England's new health regulator to fail. PMID- 22051522 TI - Preferred step frequency minimizes veering during natural human walking. AB - In the absence of visual information, humans cannot maintain a straight walking path. We examined the hypothesis that step frequency during walking affects the magnitude of veering in healthy adults. Subject walked at a preferred (1.77 +/- 0.18 Hz), low (0.8 * preferred, 1.41 +/- 0.15 Hz), and high (1.2* preferred, 2.13 +/- 0.20 Hz) step frequency with and without a blindfold. We compared the absolute differences between estimated and measured points of crossing a target line after 16 m of forward walking at the three step frequencies. There was no significant difference in veering when subjects walked at the different frequencies without a blindfold. However, the magnitude of veering was the smallest at the preferred (mean +/- SE=91.6 +/- 33.6 cm) compared with the low (204.3 +/- 43.0 cm) and high (112.7 +/- 34.0 cm) frequency gaits with a blindfold. Thus, walking at a preferred step frequency minimizes veering, which occurs in the absence of visual information. This phenomenon may be associated with the previously reported minimization of movement variability, energy cost, and attentional demand while walking at a preferred step frequency. PMID- 22051523 TI - Ethical and medicolegal issues in neuromonitoring during thyroid and parathyroid surgery: a review of the recent literature. AB - PURPOSE OF REVIEW: Neuromonitoring of the recurrent laryngeal nerve is increasingly utilized in thyroid and parathyroid surgery. Many studies have examined this practice with respect to rates of nerve injury. We have reviewed this literature with specific focus on ethical and medicolegal issues. RECENT FINDINGS: The preponderance of data fail to show that neuromonitoring significantly reduces the rates of nerve injury in thyroid and parathyroid surgery. However, potential benefits can nevertheless be identified for patients in predicting nerve injuries and reducing risks of bilateral recurrent laryngeal nerve injury. The primary ethical and medicolegal issues raised by neuromonitoring relate to setting high expectations of unproven benefit and not utilizing the technology to gain the most information for patient care decision making. SUMMARY: Neuromonitoring can provide valuable information to surgeons about the functioning of the recurrent laryngeal nerve and external branch of the superior laryngeal nerve. Surgeons should follow guidelines for optimal use of neuromonitoring but should not overestimate the benefits of neuromonitoring when discussing the technology with patients. PMID- 22051524 TI - The non-Gaussian dynamics of glycerol. AB - We have combined incoherent quasielastic neutron scattering experiments and atomistic molecular simulations to investigate the microscopic dynamics of glycerol moving away from the hydrodynamic limit. We relate changes in the momentum transfer (Q) dependence of the relaxation time to distinct changes of the single-particle dynamics. Going from small to large values of Q, a first crossover at about 0.5 A(-1) is related to the coupling of the translational diffusion dynamics to the non-Debye structural relaxation, while the second crossover at a Q-value near the main diffraction peak is associated with the Gaussian to non-Gaussian crossover of the short-time molecular dynamics, related to the decaging processes. We offer an unprecedented extension of previous studies on polymeric systems towards the case of the typical low-molecular-weight glass-forming system glycerol. PMID- 22051525 TI - Prevalence and predictors of idiopathic asymmetry in infants born preterm. AB - BACKGROUND: An idiopathic asymmetry in posture of the head is recognized as a risk factor to develop a deformational plagiocephaly (DP). In our neonatal follow up clinic, an IA is often observed in infants born preterm at term-equivalent age (TEA). AIMS: To explore (1) the prevalence of an idiopathic asymmetry in 192 infants (gestational age <=32.0 weeks) at TEA and 6 months corrected age (CA), (2) whether demographical, perinatal, and medical factors were predictors of the asymmetry, and (3) differences in motor maturation between infants with and without asymmetry. METHODS: In a retrospective study, frequencies of idiopathic asymmetry and DP, putative predictors, and Alberta Infant Motor Scale scores at 6 months CA were abstracted and analyzed with Chi(2), Mann-Whitney, logistic regression and T-test. RESULTS: The prevalence rate of a positional preference of the head at TEA was 44.8% (n=86), 10.4% (20/192) had a DP at TEA and 13% (25/192) at 6 months CA. Positional preference, multiple birth and male gender predicted the presence of DP (p<.05, odds ratio 3.0, 3.2, and 3.1 respectively). Gross motor maturity at 6 months CA was less developed in infants with a positional preference at TEA compared to preterm norms (p=0.01). CONCLUSIONS: The high prevalence of a positional preference in infants born preterm at term equivalent age requires extra alertness to prevent the development of a deformational plagiocephaly, especially in boys and twins. Although, considering the lower prevalence of plagiocephaly at 6 months CA, therapists should be aware of over treating these infants. PMID- 22051526 TI - Change in cognitive abilities over time during preschool age in low risk preterm children. AB - BACKGROUND: More information is needed on 'low-risk' preterm infants' neurological outcome so that they can be included in follow-up programs at least until school age. OBJECTIVE: To examine the neuropsychological outcome in a group of low-risk low birth weight (LBW) children without neurological impairment followed from birth to 5 years of age. PATIENTS: 26 intellectually normal children born preterm (30-34 weeks gestation) without major neurological disabilities and 23 control children born at term and matched for age, sex, and parental educational and occupational status. METHODS: Subjects already evaluated at 3 years of age underwent assessment again at 5 years using as neuropsychological outcome measures a wide range of tests including perceptual and visual-motor function, language comprehension and expression, and attention skills. RESULTS: When tested at 5 years, children born preterm still obtained significantly lower mean scores than controls on visual motor integration test (57 vs 64, p=0.01), visual perception test (41 vs 43, p=0.002) and a trend toward a lower score in the picture vocabulary test (81 vs 85.5, p=0.07). The group of premature infants and controls improved their performance over time in the neuropsychological abilities investigated and, in some skills such as visual perception. Children born preterm took longer than those born at term to reach similar performance levels, 5 versus 3 years. CONCLUSION: Ex low-risk children born preterm achieve lower scores over time in visual-motor and perceptual ability scales and in some language tests than children born at term. Like high risk premature infants even those at low risk deserve regular follow-up with long term programs. PMID- 22051527 TI - Suspected Bartonella-associated myocarditis and supraventricular tachycardia in a cat. AB - A 4-year old female spayed domestic short hair cat presented for evaluation of a tachyarrhythmia identified on routine physical examination. Supraventricular tachycardia (SVT) was identified on electrocardiogram (ECG). Echocardiogram failed to identify any structural heart disease. A positive Bartonella antibody titer was identified on serological evaluation. The cat received anti-arrhythmics for control of the SVT and azithromycin for Bartonella. After completion of antibiotic therapy, a four-fold decrease in the Bartonella antibody titer was measured and the cat was eventually weaned off anti-arrhythmic medications. At 1 week, 1 month and 3 month re-checks off all therapy, no SVT was identified. PMID- 22051528 TI - Association of QRS duration and survival in dogs with dilated cardiomyopathy: a retrospective study of 266 clinical cases. AB - OBJECTIVE: The purpose of this study was to investigate the prognostic value of QRS duration in dogs with dilated cardiomyopathy (DCM) by studying its relationship with survival time. METHODS: The medical records of dogs diagnosed with DCM were retrospectively searched for good quality ECG tracings. The QRS duration was measured from the ECG tracing and two different models were used: binary variable (dogs were divided into 2 groups based on a QRS duration of <60 ms or >=60 ms) and continuous variable. The survival times were analysed by the Kaplan-Meier method and Cox's proportional hazard model. RESULTS: 266 dogs met the inclusion and exclusion criteria. A QRS duration >=60 ms was associated with a reduced survival time compared to those with a QRS duration <60 ms (Hazard Ratio of 1.34, 95% CI 1.05-1.71, P = 0.02). When considered as a continuous variable the Hazard Ratio was 1.015 for each increase in QRS duration of 1 ms (95% CI 1.006-1.024, p = 0.001).Dogs with a QRS duration < 60 ms had a median survival time (IQ range) of 25 weeks (97-65) and dogs with a QRS duration >=60 ms had a median survival time (IQ range) of 13 weeks (3-34). CONCLUSION: The measurement of QRS duration is relatively simple to perform from a surface ECG recording. A duration >=60 ms is associated with shorter survival times in dogs with DCM, which may provide practitioners with additional prognostic information. PMID- 22051529 TI - Use of a third class in latent class modelling for the diagnostic evaluation of five infectious salmon anaemia virus detection tests. AB - In the absence of a reference standard, a latent class model (LCM) was used in this study to assess diagnostic sensitivity (DSe) and specificity (DSp) of a recently developed reverse-transcription polymerase chain reaction (RT-PCR) for infectious salmon anaemia virus (ISAV). The study included 4 populations of Atlantic salmon, and to ensure the identifiability of the LCM, four additional detection methods were used in parallel including real-time RT-PCR (qRT-PCR), virus isolation (VI), indirect fluorescent antibody test (IFAT), and a lateral flow immunoassay (LFI). While a conventional LCM assumes DSe and DSp to be constant across the populations, Nerette et al. (2008) previously reported concerns about non-constant DSp of RT-PCR, which detects viral RNA from both active and inactive viral particles. It was suspected that some ISAV recovered fish may carry residual RNA and may be more likely to test positive compared to naive fish. The various mixture distributions of the two sub-classes of non infected fish would lead to a non-constant combined DSp estimate across populations. Within a Bayesian framework, the conventional two-class LCM was extended to three classes of infection stages (naive non-infected, recovered non infected carrying RNA, and infected). The resulting analysis confirmed the existence of three classes of fish with substantially different test performances for ISAV. For infected fish, DSe of RT-PCRs and VI approximated 90%, and antibody based assays were the least sensitive (DSe around 65%). Regardless of the test, the DSp estimates on naive fish were all above 98% with LFI being in average the most specific. Only RT-PCR and qRT-PCR tested positive with the additional class of recovered fish (DSp around 30%). The true infectious status of this sub-class (i.e. viral RNA carriers) is debatable and requires further knowledge about ISAV infection dynamics at the fish level. Promising applications of multiple class estimates require adjustments of traditional test interpretation and further epidemiological knowledge of the infection dynamics at the population level. PMID- 22051530 TI - How to manage essential thrombocythemia. AB - I use the hematological, morphological and molecular criteria recently established by the World Health Organization to diagnose essential thrombocytemia. In these patients, major causes of morbidity and mortality are represented by thrombosis and bleeding, whereas progression to myelofibrosis and transformation to acute leukemia are more rare. Myelosuppressive therapy can reduce the rate of vascular complications, but there is some concern about treatment-related toxicity. Therefore, I follow a risk-oriented therapeutic approach to avoid inappropriate exposure to cytotoxic drugs on one side or suboptimal treatment on the other. Established predictors of cardiovascular events are represented by older age and previous thrombosis, whereas recent data suggest a prognostic role for novel risk factors, including leukocytosis and JAK2V617F mutational status. There is no indication for therapeutic intervention in asymptomatic, low-risk patients, while I treat high-risk patients with hydroxyurea (HU) first. Other therapeutic options, such as interferon alpha or anagrelide, may find place in selected patients including those who are resistant or intolerant to HU. I follow a risk-oriented approach also for management of pregnancy. Low-risk women are given low-dose aspirin throughout pregnancy and prophylactic low-molecular-weight heparin (LMWH) post partum, whereas LMWH throughout pregnancy and/or interferon-alpha can be required in high-risk cases. PMID- 22051531 TI - An immature immunophenotype of bone marrow mast cells predicts for multilineage D816V KIT mutation in systemic mastocytosis. AB - D816V KIT mutation of bone marrow (BM) mast cells (MC) is a common feature to systemic mastocytosis (SM) patients. Nevertheless, occurrence of the KIT mutation in BM cell compartments other than MC is associated with progression to more aggressive forms of the disease and poor outcome in indolent SM (ISM). Here, we assessed the potential association between the immunophenotype of MC and multilineage KIT mutation in the BM of SM patients through the investigation of the flow cytometric protein expression profile (PEP) of bone marrow mast cells (BMMC) from 70 control individuals and 206 SM patients, classified according to the WHO (World Health Organization), and the degree of involvement of BM hematopoiesis by the D816V KIT mutation; additionally, we developed a score-based class prediction algorithm for the detection of SM cases with multilineage mutation. Our results show that aberrant expression of CD25 with a FcERI(lo), FSC(lo), SSC(lo) and CD45(lo) immature phenotype of BMMC, in the absence of coexisting normal MC in the BM, was associated with multilineage involvement by the D816V KIT mutation, regardless of the diagnostic subtype of the disease (for example, indolent vs aggressive SM), which supports the utility of the immunophenotype of BMMC as a surrogate marker to screen for multilineage KIT mutation in ISM. PMID- 22051532 TI - beta-catenin is dynamically stored and cleared in multiple myeloma by the proteasome-aggresome-autophagosome-lysosome pathway. PMID- 22051533 TI - Antigen receptor stereotypy across B-cell lymphoproliferations: the case of IGHV4 59/IGKV3-20 receptors with rheumatoid factor activity. PMID- 22051534 TI - Notch induces human T-cell receptor gammadelta+ thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway. AB - In wild-type mice, T-cell receptor (TCR) gammadelta(+) cells differentiate along a CD4 CD8 double-negative (DN) pathway whereas TCRalphabeta(+) cells differentiate along the double-positive (DP) pathway. In the human postnatal thymus (PNT), DN, DP and single-positive (SP) TCRgammadelta(+) populations are present. Here, the precursor-progeny relationship of the various PNT TCRgammadelta(+) populations was studied and the role of the DP TCRgammadelta(+) population during T-cell differentiation was elucidated. We demonstrate that human TCRgammadelta(+) cells differentiate along two pathways downstream from an immature CD1(+) DN TCRgammadelta(+) precursor: a Notch-independent DN pathway generating mature DN and CD8alphaalpha SP TCRgammadelta(+) cells, and a Notch dependent, highly proliferative DP pathway generating immature CD4 SP and subsequently DP TCRgammadelta(+) populations. DP TCRgammadelta(+) cells are actively rearranging the TCRalpha locus, and differentiate to TCR(-) DP cells, to CD8alphabeta SP TCRgammadelta(+) cells and to TCRalphabeta(+) cells. Finally, we show that the gammadelta subset of T-cell acute lymphoblastic leukemias (T-ALL) consists mainly of CD4 SP or DP phenotypes carrying significantly more activating Notch mutations than DN T-ALL. The latter suggests that activating Notch mutations in TCRgammadelta(+) thymocytes induce proliferation and differentiation along the DP pathway in vivo. PMID- 22051535 TI - Roth versus MBT: does bracket prescription have an effect on the subjective outcome of pre-adjusted edgewise treatment? AB - The aim was to determine if bracket prescription has any effect on the subjective outcome of pre-adjusted edgewise treatment as judged by professionals. This retrospective observational assessment study was undertaken in the Orthodontic Department of the Charles Clifford Dental Hospital, Sheffield, UK. Forty sets of post-treatment study models from patients treated using a pre-adjusted edgewise appliance (20 Roth and 20 MBT) were selected. The models were masked and shown in a random order to nine experienced orthodontic clinicians, who were asked to assess the quality of the outcome, using a pre-piloted questionnaire. The principal outcome measure was the Incisor and Canine Aesthetic Torque and Tip (ICATT) score for each of the 40 post-treatment models carried out by the nine judges. A two-way analysis of variance was undertaken with the dependent variable, total ICATT score and independent variables, Bracket prescription (Roth or MBT) and Assessor. There were statistically significant differences between the subjective assessments of the nine judges (P<0.001), but there was no statistically significant difference between the two bracket prescriptions (P = 0.900). The best agreement between a clinician's judgment of prescription used and the actual prescription was fair (kappa statistic 0.25; CI -0.05 to 0.55). The ability to determine which bracket prescription was used was no better than chance for the majority of clinicians. Bracket prescription had no effect on the subjective aesthetic judgments of post-treatment study models made by nine experienced orthodontists. PMID- 22051536 TI - Comparison of tooth displacement between buccal mini-implants and palatal plate anchorage for molar distalization: a finite element study. AB - The purposes of this study were to mechanically evaluate distalization modalities through the application of skeletal anchorage using finite element analysis. Base models were constructed from commercial teeth models. A finite element model was created and three treatment modalities were modified to make 10 models. Modalities 1 and 2 placed mini-implants in the buccal side, and modality 3 placed a plate on the palatal side. Distalization with the palatal plate in modality 3 showed bodily molar movement and insignificant displacement of the incisors. Placing mini-implants on the buccal side in modalities 1 and 2 caused the first molar to be distally tipped and extruded, while the incisors were labially flared and intruded. Distalization with the palatal plate rather than mini-implants on the buccal side provided bodily molar movement without tipping or extrusion. It is recommended to use our findings as a clinical guide for the application of skeletal anchorage devices for molar distalization. PMID- 22051537 TI - A finite element simulation of initial movement, orthodontic movement, and the centre of resistance of the maxillary teeth connected with an archwire. AB - The purpose of this article is to simulate long-term movement of maxillary teeth connected with an archwire and to clarify the difference between the initial tooth movement and the long-term orthodontic movement. Initial tooth movement was calculated based on the elastic deformation of the periodontal ligament. Orthodontic tooth movement was simulated based on the bone remodeling law of the alveolar bone, while consequentially updating the force system. In the initial tooth movement, all teeth tipped individually due to an elastic deflection of the archwire. In the long-term movement, the maxillary teeth moved as one united body, as if the archwire were a rigid material. Difference of both movement patterns was due to the change in force system during tooth movement. The long term movement could not be predicted from the initial tooth movement. Movement pattern and location of the centre of resistance in the long-term movement were almost the same as those in the initial tooth movement as calculated by assuming the archwire to be a rigid material. PMID- 22051538 TI - Facial aesthetics and perceived need for further treatment among adults with repaired cleft as assessed by cleft team professionals and laypersons. AB - The objectives of this study were to compare the ratings of professionals and laypeople with and without a cleft regarding the facial aesthetics of adult patients previously treated for orofacial clefting. The necessity for further treatment, as perceived by the respective groups, is also compared. The design of the study was a cross-sectional study. Professionals (two plastic surgeons, one dentist, one orthodontist, and one psychologist) and laypeople (one male and one female adult without a cleft and one male and one female adult with a cleft) were recruited to rate photographs of 80 non-syndromic cleft patients treated by the Australian Craniofacial Unit from 1975 to 2009. Facial aesthetics were measured by a visual analogue scale (VAS; 0-100 mm). High values indicated good aesthetics. Necessity for further treatment was also measured by a VAS (0-100 mm). High values indicated high perceived need for further treatment. The professionals rated facial aesthetics significantly lower and had a lower perception of need for further treatment than the raters with and without a cleft. The laypeople with a cleft rated facial aesthetics significantly higher and had a lower perceived need for further treatment than laypeople without a cleft. The non-surgical professionals rated facial aesthetics significantly lower and had a lower perceived need for further treatment than the surgical professionals. Differences exist in the facial aesthetics ratings and perceived need for further surgery between professionals and laypeople with and without a cleft. This should be considered when managing cleft treatment expectations. PMID- 22051539 TI - Recombinant medaka (Oryzias melastigmus) pro-hepcidin: Multifunctional characterization. AB - Recently, two hepcidin variant genes (Om-hep1 and Om-hep2) were identified in a model fish marine medaka and both were highly induced in vivo with bacterial challenge, suggesting that the medaka hepcidin may have a similar function to other reported teleostean hepcidins. In the present study, the antibacterial, antiviral and antitumor activities of Om-hep1 were determined using its synthetic and recombinant pro-peptides. The recombinant pro-hepcidin1 was expressed in Escherichia coli and an effective method to produce recombinant Pro-Omhep1 was developed in order to obtain a right folded structure. The results showed that both the synthetic mature peptide and recombinant pro-peptide had similar antibacterial activity against Gram-positive and negative bacteria. In particular, both the synthetic mature Om-hep1 and recombinant Pro-Omhep1 inhibited the viral replication of white spot syndrome virus in the hematopoietic tissue cells of the crayfish Cherax quadricarinatus. Om-hep1 also presented antitumor activity on the cultured human hepatocellular carcinoma cells. In addition, the antimicrobial mechanism of Om-hep1 was measured and it was found that Om-hep1 was likely to be non-membranolytic. The recombinant Pro-Omhep1 performed better biological activity compared to the synthetic mature Om-hep1. This study suggested that Om-hep1 was likely to be an important multifunction protein involved in various resistance actions in the marine medaka immune system. PMID- 22051540 TI - Phosphoric acid functionalized mesoporous organo-silica (EPO) as the adsorbent for in situ enrichment and isotope labeling of endogenous phosphopeptides. AB - Ti(4+)-EPO nanoparticles were adopted as the adsorbent for in situ solid phase enrichment and isotope labeling of endogenous phosphopeptides, which has great potential application in high-throughput analyses of biological samples for screening and discovery of disease-specific biomarkers. PMID- 22051541 TI - Localization of small parathyroid adenomas using modified 4-dimensional computed tomography/ultrasound. AB - OBJECTIVE: To investigate whether parathyroid gland weight has an impact on the accuracy of preoperative localization of parathyroid adenomas with modified 4 dimensional computed tomography/ultrasound. And to determine if the weight of parathyroid adenomas can be calculated accurately based on the dimensions of the gland on the CT images. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care hospital. SUBJECTS AND METHODS: One hundred forty-two patients who had a preoperative modified 4-dimensional computed tomography/ultrasound and underwent parathyroidectomy for hyperparathyroidism due to a parathyroid adenoma between 1998 and 2009. Charts were reviewed to identify (1) the sensitivity and specificity for localization of parathyroid adenomas according to gland weight and (2) correlation between preoperative estimate of parathyroid weight and the surgical weight of the parathyroid gland. RESULTS: Modified 4-dimensional computed tomography/ultrasound displayed 92% sensitivity for localizing adenomas weighing <150 mg to the correct side of the neck (95% confidence interval [CI], 65%-99%), 100% sensitivity for glands weighing 150 to 500 mg (95%-100%), and 98% sensitivity for glands weighing >500 mg (92%-100%). For localization to the correct quadrant of the neck, sensitivity was 75% (95% CI, 47%-91%) for glands weighing <150 mg, 89% (79%-95%) for those weighing 150 to 500 mg, and 94% (85% 97%) for glands weighing >500 mg. A positive correlation was seen between the preoperative weight estimate based on imaging and the operative weight of the gland, with a Pearson correlation coefficient of 0.96. CONCLUSION: Modified 4 dimensional computed tomography/ultrasound can closely predict the weight of parathyroid glands preoperatively and has good sensitivity for localization of adenomas, even in glands weighing less than 150 mg. PMID- 22051542 TI - Protective effect of erdosteine against cisplatin-induced ototoxicity in a guinea pig model. AB - OBJECTIVE: Cisplatin is a commonly used chemotherapeutic agent. One of its major dose-limiting side effects is ototoxicity. No treatment has yet been approved for this condition. The objective of this study was to determine the potential protective effect of a systemic administration of erdosteine against cisplatin induced ototoxicity. STUDY DESIGN: A prospective controlled trial conducted in an animal model. SETTING: Animal care research facilities of The Montreal Children's Hospital Research Institute. SUBJECTS AND METHODS: A total of 27 guinea pigs were assigned to 4 groups, each receiving a different concentration of intraperitoneal erdosteine: group 1 (control group; n = 9) did not receive erdosteine, group 2 (n = 6) received 100 mg/kg/d, group 3 (n = 6) received 200 mg/kg/d, and group 4 (n = 6) received 500 mg/kg/d. The animals in the experimental groups received the erdosteine injection daily for 4 days. All of the animals received 12 mg/kg of intraperitoneal cisplatin. Auditory brainstem response threshold shifts were measured at 4 frequencies (8, 16, 20, and 25 kHz) for all groups. Scanning electron microscopy and outer hair cell counts were performed to assess the protective effect of erdosteine. RESULTS: Significant protection was observed in groups 3 and 4 at 25 kHz. These findings are supported by outer hair cell counts by scanning electron microscopy. CONCLUSION: A systemic administration of erdosteine appears to provide an otoprotective effect at high frequencies for cisplatin-induced ototoxicity. PMID- 22051543 TI - Face and content validation of a virtual reality temporal bone simulator. AB - OBJECTIVE: To validate the VOXEL-MAN TempoSurg simulator for temporal bone dissection. STUDY DESIGN: Prospective international study. SETTING: Otolaryngology departments of 2 academic health care institutions in the United Kingdom and United States. SUBJECTS AND METHODS: Eighty-five subjects were recruited consisting of an experienced and referent group. Participants performed a standardized familiarization session and temporal bone dissection task. Realism, training effectiveness, and global impressions were evaluated across 21 domains using a 5-point Likert-type scale. A score of 4 was the minimum threshold for acceptability. RESULTS: The experienced group comprised 25 otolaryngology trainers who had performed 150 mastoid operations. The referent group comprised 60 trainees (mean otolaryngology experience of 2.9 years). Familiarization took longer in the experienced group (P = .01). User-friendliness was positively rated (mean score 4.1). Seventy percent of participants rated anatomical appearance as acceptable. Trainers rated drill ergonomics worse than did trainees (P = .01). Simulation temporal bone training scored highly (mean score 4.3). Surgical anatomy, drill navigation, and hand-eye coordination accounted for this. Trainees were more likely to recommend temporal bone simulation to a colleague than were trainers (P = .01). Transferability of skills to the operating room was undecided (mean score 3.5). CONCLUSION: Realism of the VOXEL-MAN virtual reality temporal bone simulator is suboptimal in its current version. Nonetheless, it represents a useful adjunct to existing training methods and is particularly beneficial for novice surgeons before performing cadaveric temporal bone dissection. Improvements in realism, specifically drill ergonomics and visual-spatial perception during deeper temporal bone dissection, are warranted. PMID- 22051544 TI - Highly sensitive detection of Salmonella typhi using surface aminated polycarbonate membrane enhanced-ELISA. AB - The identification of pathogenic bacteria in water is important for addressing preventive and treatment issues regarding health and safety. A highly sensitive and specific solid-phase sandwich ELISA procedure was developed for the detection of typhoid causing extremely lethal water borne pathogen Salmonella typhi (S. typhi) on modified isopore polycarbonate (PC) black membranes. PC membranes were chemically derivatized to generate amino groups on the surface maintaining their pysico-optico properties. Surface modified PC membranes were characterized by ATR FTIR spectrometer, goniometer and scanning electron microscope. Polyclonal somatic 'O' type antibodies (Abs) against whole cell S. typhi were immobilized on them by following the amine glutaraldehyde chemistry. Antibody immobilized membranes captured S. typhi from buffer solution and this complex was detected colourimetrically using HRP labelled S. typhi Ab. A detection limit of 2*10(3)cells/ml of bacteria was achieved with the modified PC membranes without any pre-enrichment step as against 10(6)-10(7)CFU/ml of bacteria by typical ELISA method. The assay was demonstrated to be specific for the target bacteria when compared with other cross-reactant water borne pathogens. The intra- and inter assay precision for 10(4) and 10(5)cells/ml was 5.3-7.4 and 10.3-19.7% respectively. The developed immunoassay for the detection of S. typhi is simple, easy to handle, sensitive specific, reproducible and cost effective in comparison with the commercially existing immunochromatographic assays. PMID- 22051545 TI - Ultra-sensitive suspended graphene nanocomposite cancer sensors with strong suppression of electrical noise. AB - The cancer sensor based on suspended layer-by-layer self-assembled graphene reported in the paper exhibits an ultra high sensitivity due to graphene material properties in nature. By simply immersing the substrate alternatively into charged graphene suspensions and polyions, graphene nanoplatelets are self assembled in the channel as the sensing region, followed by SF(6) dry etching to suspend the structure. Conductance shift curves demonstrate that the suspended graphene sensors functionalized with specific anti-PSA antibodies as bioreceptor are capable of detecting prostate specific antigen down to 0.4 fg/ml (11 aM), at least one order of magnitude lower than unsuspended devices. The noise spectra analysis confirms the lower level of 1/f noise in suspended graphene devices. Carbon nanotube sensor under the same conditions of design, manufacture, and measurement are implemented to compare with graphene devices, showing the prominent advantages of graphene as a sensing material. PMID- 22051546 TI - Paper-based chemiluminescence ELISA: lab-on-paper based on chitosan modified paper device and wax-screen-printing. AB - A novel lab-on-paper device combining the simplicity and low-cost of microfluidic paper-based analytical devices (MUPADs) and the sensitivity and selectivity of chemiluminescence ELISA (CL-ELISA) for the high-throughput, rapid, stable and reusable point-of-care testing is presented here. Chitosan was used to modify MUPADs to covalently immobilize antibodies on MUPADs. Thus, sandwich CL-ELISA on MUPADs can be easily realized for further development of this technique in sensitive, specific and low-cost application. The paper device was fabricated by a low-cost, simple, and rapid wax-screen-printing method. Using tumor markers and paper microzone plate as model, the application test of this paper-based CL-ELISA was successfully performed with a linear range of 0.1-35.0 ng mL(-1) for alpha fetoprotein, 0.5-80.0 U mL(-1) for cancer antigen 125 and 0.1-70.0 ng mL(-1) for carcinoembryonic antigen. Since the cutoff values of the three tumor markers in clinical diagnosis are 25 ng mL(-1), 35 U mL(-1) and 5 ng mL(-1), the sensitivity and linear ranges of the proposed method were enough for clinical application. In addition, this lab-on-paper immunodevice can provide reproducible results upon storage at 4 degrees C (sealed) for at least 5 weeks. Ultimately, this novel chitosan modification and wax-screen-printing methodology for MUPADs can be readily translated to other signal reporting mechanism including electrochemiluminescence and photoelectrochemistry, and other receptors such as enzyme receptors and DNA receptors for determination of DNA, proteins and small molecules in point-of-care testing. PMID- 22051547 TI - Monoclinic honeycomb-layered compound Li3Ni2SbO6: preparation, crystal structure and magnetic properties. AB - Two synthetic routes-ion-exchange preparation from layered Na(3)Ni(2)SbO(6) at 300 degrees C and direct solid-state synthesis at 1150 degrees C resulted in layered Li(3)Ni(2)SbO(6), a cation-ordered derivative from the rocksalt type. The Fddd form reported earlier could not be reproduced. According to the XRD Rietveld analysis, Li(3)Ni(2)SbO(6) is a pseudohexagonal monoclinic structure, C2/m, with a = 5.1828(2) A, b = 8.9677(3) A, c = 5.1577(2) A, beta = 109.696(2) degrees . No Li/Ni mixed occupancy was detected. At high temperatures, the magnetic susceptibility follows the Curie-Weiss law with a positive value of Weiss temperature, ~8 K, indicating a predominance of ferromagnetic interactions. However, Li(3)Ni(2)SbO(6) orders antiferromagnetically at T(N)~ 15 K. The effective magnetic moment is 4.3 MU(B)/f.u. which satisfactorily agrees with theoretical estimations assuming high-spin configuration of Ni(2+) (S = 1). Electron spin resonance (ESR) spectra show single Lorentzian shape line attributed to Ni(2+) ion in octahedral coordination. The absorption is characterized by isotropic temperature independent effective g-factor g = 2.150 +/- 0.005. In accordance with the layered honeycomb crystal structure determined for Li(3)Ni(2)SbO(6), the superexchange interaction between Ni(2+) ions through Ni-O-Ni pathways within Ni(2)SbO(6) layers are assumed to be ferromagnetic, while the dominant interaction between layers is antiferromagnetic. PMID- 22051548 TI - Neurophysiological changes after intramuscular injection of botulinum toxin. AB - Botulinum toxin (BT) acts peripherally by inhibiting acetylcholine release from the presynaptic neuromuscular terminals and by weakening muscle contraction. Therefore, its clinical benefit is primarily due to its peripheral action. As a result, local injection of BT has become a successful and safe tool in the treatment of several neurological and non-neurological disorders. Studies in animals have also shown that the toxin can be retrogradely transported and even transcytosed to neurons in the central nervous system (CNS). Further human studies have suggested that BT could alter the functional organisation of the CNS indirectly through peripheral mechanisms. BT can interfere with and modify spinal, brainstem and cortical circuits, including cortical excitability and plasticity/organisation by altering spindle afferent inflow directed to spinal motoneurons or to the various cortical areas. It is well demonstrated that the distant CNS effects of BT treatment parallel the peripheral effect, although there is limited evidence as to the cause of this. Therefore, further studies focussed on central changes after BT treatment is needed for a better understanding of these non-peripheral effects of BT. PMID- 22051549 TI - Aquatic toxicity and ecological risk assessment of seven parabens: Individual and additive approach. AB - In the present study, aquatic concentrations of seven parabens were determined in urban streams highly affected by treated or untreated domestic sewage in Tokushima and Osaka, Japan. The detected highest concentrations were 670, 207, and 163ngl(-1) for methylparaben, n-propylparaben, and n-butylparaben, respectively in sampling sites with watershed area of no sewer system in Tokushima. Conventional acute/chronic toxicity tests were conducted using medaka (Oryzias latipes), Daphnia magna, and Psuedokirchneriella subcapitata for four parabens, which was consistent with our previous study on three parabens, n butylparaben, i-butylparaben, and benzylparaben. The aquatic toxicity on fish, daphnia, and algae was weaker for the parabens with a shorter alkyl chain than those with a longer alkyl chain as predicted by their hydrophobicity. Medaka vitellogenin assays and DNA microarray analysis were carried out for methylparaben and found induction of significant vitellogenin in male medaka at 630MUgl(-1) of methylparaben, while the expression levels of genes encoding proteins such as choriogenin and vitellogenin increased for concentrations at 10MUgl(-1) of methylparaben. Measured environmental concentrations (MECs) of seven parabens in Tokushima and Osaka were divided by predicted no effect concentrations (PNECs) and hazard quotient (MEC/PNEC) was determined for individual parabens. The MEC/PNEC was highest for n-propylparaben and was 0.010 followed by n-butylparaben (max. of 0.0086) and methylparaben (max. of 0.0042). The sum of the MEC/PNEC for the seven parabens was 0.0049. Equivalence factors were assigned for each paraben on the basis of the toxicity of n-butylparaben for each species, and n-butylparaben equivalence was calculated for the measured environmental concentrations. The MEC/PNEC approach was also conducted for the n butylparaben-based equivalence values. The maximum MEC/PNEC was 0.018, which is lower than the trigger level for further detailed study such as large-scale monitoring for chronic toxicity tests including full-life cycle tests for fish. PMID- 22051550 TI - Arsenic accumulation and distribution in relation to young seedling growth in Atriplex atacamensis Phil. AB - Even at trace levels, arsenic is of environmental and health concern due to its high toxicity. The xerohalophyte plant species Atriplex atacamensis grows on an arsenic-contaminated mining area in North Chile. Young seedlings that were grown from seeds collected from these plants were grown in a nutrient solution under controlled environmental conditions and were exposed for 14 and 28 days to 0, 100 or 1000 MUM arsenate. More than 75% of the plants that were exposed to the highest As dose survived until the end of the treatment. The seedling growth was reduced (100 MUM As) or inhibited (1000 MUM As) in the stress conditions, but the plants were able to efficiently close their stomata and perform osmotic adjustments to avoid secondary water stress. Arsenic accumulated up to 400 MUg g( 1) DW in the shoots and 3500 MUg g(-1) DW in the roots. Arsenate drastically impaired the P content and increased glycinebetaine content, although no arsenobetaine was found in the tissues. With the exception of arsenite and arsenate, no As-containing organic compound was detected. Arsenic was not excreted by the trichomes that were present at the leaf surface. Although an increase in the total level of non-protein thiols suggested that arsenite fixation on the sulfhydryl groups could occur in the stressed tissues, the majority of the soluble arsenic remained in its oxidized state As(V). Arsenate induced an increase in the free soluble polyamine concentrations in all of the organs, and it increased the proportion of spermidine and spermine and decreased the proportion of putrescine in the polyamine pool. Therefore, it is likely that these polycationic molecules may assist in arsenate sequestration in the stressed tissues, and A. atacamensis may represent a promising plant species that can be tested in field trials for its phytomanagement of As-contaminated sites in desert areas. PMID- 22051551 TI - Atmospheric corrosion of brass in outdoor applications: patina evolution, metal release and aesthetic appearance at urban exposure conditions. AB - Short (days, weeks) and long-term (months, years) non-sheltered field exposures of brass (15, and 20 wt.% Zn) and copper sheet have been conducted in three European cities (Milan, Stockholm, Madrid) to generate an in-depth time-dependent understanding of patina evolution, corrosion rates, aesthetic appearance, metal release and degree of dezincification in relation to detailed bulk and surface characteristics prior to exposure. This has been accomplished by using a multitude of surface and bulk analytical tools, chemical analysis and colorimetric investigations. Small differences in surface finish and local variations in nobility observed for the non-exposed brass alloys resulted in slight differences in corrosion initiation. Despite different kinetic behaviour and relative surface distributions of zinc- and copper-rich patina constituents, similar phases were identified with copper-rich phases rapidly dominating the outermost patina layer in Milan, compared to Madrid and Stockholm showing both copper- and zinc-rich phases. As a consequence of differences in surface coverage of copper- and zinc-rich corrosion products at the different sites, the release ratios of copper to zinc varied concordantly. The released amount of zinc to copper (Zn/Cu) was for both alloys and test sites always higher compared to the bulk composition showing a preferential release of zinc. The amount of released copper from the brass alloys was on an average 30-40% lower compared to copper sheet at all test sites investigated. Significantly lower annual total release rates of copper and zinc compared with annual corrosion rates were evident for both brass alloys at all sites. PMID- 22051552 TI - p53-Mediated regulation of hepatic lipid metabolism: forging links between metabolism, atherogenesis, and cancer. PMID- 22051553 TI - The LDLR deficient mouse as a model for aortic calcification and quantification by micro-computed tomography. AB - OBJECTIVE: Patients with familial hypercholesterolemia (FH) due mutations in the low-density lipoprotein receptor (LDLR) suffer premature aortic calcification, an effect that is age- and gene dosage-dependent and cholesterol level independent later in life. To better understand this process, we examined a murine model. METHODS: We compared chow fed Ldlr(-/-) mice to controls at 6, 12 and 18 months and on a Western diet (WD) at 6 months. Additionally, we compared controls to Ldlr(-/-) mice and transgenic mice Tg(Pcsk9) overexpressing PCSK9, which promotes LDLR degradation. Aortas were perfused-fixed, embedded in paraffin, and sections were stained with alizarin red. Micro-computerized tomography (micro-CT) was used to quantify vascular calcification. RESULTS: Ldlr(-/-) mice develop calcification in the ascending, transverse aorta and neck vessels with a distribution similar to that of human. Calcification was most prominent in 18-month-old Ldlr(-/-) mice fed a chow diet and in 6-month-old Ldlr(-/-) mice fed a WD. Interestingly, Tg(Pcsk9) mice fed a WD develop aortic calcifications as well. Histology confirmed that the calcification were predominantly sub-intimal. Marked expression of LRP5 and WNT was observed in the Ldlr(-/-) and Tg(Pcsk9) models, but not in age-matched controls. CONCLUSIONS: The two mouse models develop aortic calcification in an age- and diet-dependent manner. Abnormal regulation of the LRP5/Wnt pathway may play a role in the calcification process. Further analysis of these aortic calcification models using this micro-CT imaging technique may provide a better understanding of the link between FH and arterial calcification. PMID- 22051554 TI - Relative blindsight arises from a criterion confound in metacontrast masking: implications for theories of consciousness. AB - Relative blindsight is said to occur when different levels of subjective awareness are obtained at equality of objective performance. Using metacontrast masking, Lau and Passingham (2006) reported relative blindsight in normal observers at the shorter of two stimulus-onset asynchronies (SOAs) between target and mask. Experiment 1 replicated the critical asymmetry in subjective awareness at equality of objective performance. We argue that this asymmetry cannot be regarded as evidence for relative blindsight because the observers' responses were based on different attributes of the stimuli (criterion contents) at the two SOAs. With an invariant criterion content (Experiment 2), there was no asymmetry in subjective awareness across the two SOAs even though objective performance was the same. Experiment 3 examined the effect of criterion level on estimates of relative blindsight. Collectively, the present results question whether metacontrast masking is a suitable paradigm for establishing relative blindsight. Implications for theories of consciousness are discussed. PMID- 22051555 TI - Levels of processing influences both recollection and familiarity: evidence from a modified remember-know paradigm. AB - A modified Remember/Know (RK) paradigm was used to investigate reported subjective awareness during retrieval. Levels of processing (shallow vs. deep) was manipulated at study. Word pairs (old/new or new/new) were presented during test trials, and participants were instructed to respond "remember" if they recollected one of the two words, "know" if the word was familiar in the absence of recollection, or "new" if they judged both words to be new. Participants were then required to indicate which of the 2 words was old (2AFC recognition). With the standard RK proportions, deeper processing at study increased remember proportions and decreased know proportions, but this dissociation was not shown with the 2AFC proportion correct measure which instead demonstrated robust LOP effects for both remember and know trials, suggesting that the know proportion measure severely distorts the nature of LOP effects on familiarity. PMID- 22051557 TI - Dr. Guarneri honored at Bravewell leadership event. PMID- 22051558 TI - Meditation: the controlled psychophysical self-regulation process that works. AB - The Schwartz Report tracks emerging trends that will affect the world, particularly the United States. For EXPLORE, it focuses on matters of health in the broadest sense of that term, including medical issues, changes in the biosphere, technology, and policy considerations, all of which will shape our culture and our lives. PMID- 22051559 TI - The role of inspiration in scientific scholarship and discovery: views of theistic scientists. AB - This qualitative research study examined the ways those who identify themselves as theistic scientists and scholars experience inspiration, as defined as divine guidance or influence, in their scientific scholarship and discovery. It also explored participants' beliefs about how scientists and scholars can seek and prepare to receive inspiration in their work. Open-ended surveys of 450 participants from the behavioral and natural sciences and from a variety of religious backgrounds were analyzed for content themes in the areas of experiences with inspiration, preparing to receive inspiration, and further thoughts on inspiration in science. The themes extracted indicated that these scientists and scholars have experienced inspiration throughout all stages of the research process. They also believe that certain practices and virtues, such as openness to inspiration and nurturing a relationship with God, can help scientists and scholars be more prepared to receive inspiration in their work. PMID- 22051560 TI - The almost obvious case for a transcendental understanding of life. AB - The follow-up to the Human Genome Project has found very little to connect variations in our DNA blueprints to some of our basic individual characteristics. This very surprising "missing heritability" problem, plus a number of existing underappreciated challenges to the DNA-based model, together are consistent with an underlying complementary transcendental contribution to life. Some of the behavioral challenges for DNA and the material-only model are quite suggestive of transcendental contributions. This possible overlap between an apparent hole in the scientific understanding of life and the common premodern transcendental perspective is introduced here. PMID- 22051561 TI - Mirror box therapy: seeing is believing. AB - Working with patients with different chronic pain syndromes can be challenging. Pharmacological therapies are often associated with variety of side effects. Mind body modalities are thought to play a role; however, the lack of clear consensus and large body of clinical experience makes it hard to provide good evidence based recommendation to most of our chronic pain patients. In recent years the Phantom Limb Pain (PLP) and to some degree Complex Regional Pain Syndrome (CRPS) may prove to be an exception. In this review we summarize the current evidence supporting use of Mirror Box Therapy and its successor, Immersive Virtual Reality. PMID- 22051562 TI - Effects of mass consciousness: changes in random data during global events. AB - A long-term, continuing experiment is designed to assess the possibility that correlations may occur in synchronized random data streams generated during major world events. The project is motivated by numerous experiments that suggest that the behavior of random systems can be altered by directed mental intention, and related experiments showing subtle changes associated with group coherence. Since 1998, the Global Consciousness Project (GCP) has maintained a global network of random number generators (RNGs), recording parallel sequences of random data at 65 sites around the world. A rigorous experiment tests the hypothesis that data from the RNG network will deviate from expectation during times of "global events," defined as transitory episodes of widespread mental and emotional reaction to major world events. An ongoing replication experiment measures correlations across the network during the designated events, and the result from over 345 formal hypothesis tests departs substantially from expectation. A composite statistic for the replication series rejects the null hypothesis by more than six standard deviations. Secondary analyses reveal evidence of a second, independent correlation, as well as temporal and spatial structure in the data associated with the events. Controls exclude conventional physical explanations or experimental error as the source of the measured deviations. The experimental design constrains interpretation of the results: they suggest that some aspect of human consciousness is involved as a source of the effects. PMID- 22051563 TI - A systematic review of the literature on the chiropractic care of patients with autism spectrum disorder. AB - BACKGROUND: In addition to impacting the affected child and his/her family's quality of life, recent estimates place the lifetime cost for an individual with ASD at $3.2 million and $35 billion for the entire birth cohort. Given the clinical heterogeneity of ASD, treatment approaches are multidisciplinary including alternative therapies, particularly when no pharmaceutical agent is effective for the core symptoms of ASD. Chiropractic is a popular alternative therapy for children. A systematic review of the literature was performed to provide context for future research endeavors in this field. METHODS: A systematic review of the literature on the chiropractic care of patients with ASD utilized 8 databases. Eligibility criteria for inclusion included: (1) the study was a primary investigation/report published in an English peer-reviewed journal; (2) the study involved patients <=18 years; and (3) patients are diagnosed with autism, Asperger's Syndrome, PDD-NOS, or ASD. RESULTS: Our systematic review of the literature revealed a total of five articles consisting of three case reports, one cohort study and one randomized comparison trial. The literature is lacking on documenting the chiropractic care of children with ASD. DISCUSSION: At the heart of the core symptoms of ASD (ie, impaired social interactions, deficits in communication and repetitive or restricted behavioral patterns) is abnormal sensory processing. Preliminary studies indicate that the chiropractic adjustment may attenuate sensorimotor integration based on somatosensory evoked potentials studies. CONCLUSION: We encourage further research for definitive studies on chiropractic's effectiveness for ASD. However, given the ineffectiveness of pharmaceutical agents, a trial of chiropractic care for sufferers of autism is prudent and warranted. PMID- 22051565 TI - Advancing integration through evidence informed practice: Northwestern Health Sciences University's integrated educational model. PMID- 22051566 TI - Constructing ecologies. AB - We synthesize the generic properties of ecologically realistic multi-trophic level models and define criteria for ecological realism. We define an "ecospace" in which all ecologically realistic dynamics are confined, and construct "resource rays" that define the resources available to each species at every point in the ecospace. Resource rays for a species are lines from a vertex of maximum resource to the opposite boundary where no resources are available. The growth functions of all biota normally decrease along their resource rays, and change sign from positive to negative. This property prescribes that each species must have a zero isosurface within the ecospace. We illustrate our conditions on a highly cited three trophic level model from population dynamics, showing how to extend this system biologically consistently to a closed ecological system. Our synthesis extends the concept of carrying capacity of population models to explicitly include exhaustion of limiting resources, and so allows for population biology models to be considered as ecologically closed systems with respect to a key limiting nutrient. This approach unifies many theoretical and applied models in a common biogeochemical framework, facilitates better understanding of the key structures of complex ecologies, and suggests strategies for efficient design of experiments. PMID- 22051567 TI - Animal social networks as substrate for cultural behavioural diversity. AB - We used individual-based stochastic models to examine how social structure influences the diversity of socially learned behaviour within a non-human population. For continuous behavioural variables we modelled three forms of dyadic social learning, averaging the behavioural value of the two individuals, random transfer of information from one individual to the other, and directional transfer from the individual with highest behavioural value to the other. Learning had potential error. We also examined the transfer of categorical behaviour between individuals with random directionality and two forms of error, the adoption of a randomly chosen existing behavioural category or the innovation of a new type of behaviour. In populations without social structuring the diversity of culturally transmitted behaviour increased with learning error and population size. When the populations were structured socially either by making individuals members of permanent social units or by giving them overlapping ranges, behavioural diversity increased with network modularity under all scenarios, although the proportional increase varied considerably between continuous and categorical behaviour, with transmission mechanism, and population size. Although functions of the form e(c)1(m)-(c)2 + (c)3(Log(N)) predicted the mean increase in diversity with modularity (m) and population size (N), behavioural diversity could be highly unpredictable both between simulations with the same set of parameters, and within runs. Errors in social learning and social structuring generally promote behavioural diversity. Consequently, social learning may be considered to produce culture in populations whose social structure is sufficiently modular. PMID- 22051568 TI - A mathematical model of tumor-immune interactions. AB - A mathematical model of the interactions between a growing tumor and the immune system is presented. The equations and parameters of the model are based on experimental and clinical results from published studies. The model includes the primary cell populations involved in effector T-cell mediated tumor killing: regulatory T cells, helper T cells, and dendritic cells. A key feature is the inclusion of multiple mechanisms of immunosuppression through the main cytokines and growth factors mediating the interactions between the cell populations. Decreased access of effector cells to the tumor interior with increasing tumor size is accounted for. The model is applied to tumors with different growth rates and antigenicities to gauge the relative importance of various immunosuppressive mechanisms. The most important factors leading to tumor escape are TGF-beta induced immunosuppression, conversion of helper T cells into regulatory T cells, and the limitation of immune cell access to the full tumor at large tumor sizes. The results suggest that for a given tumor growth rate, there is an optimal antigenicity maximizing the response of the immune system. Further increases in antigenicity result in increased immunosuppression, and therefore a decrease in tumor killing rate. This result may have implications for immunotherapies which modulate the effective antigenicity. Simulation of dendritic cell therapy with the model suggests that for some tumors, there is an optimal dose of transfused dendritic cells. PMID- 22051569 TI - Exercise increases tryptophan availability to the brain in older men age 57-70 years. AB - PURPOSE: Many aspects of serotonergic activity, both central and peripheral in origin, undergo significant changes with human aging. These alterations might predispose elderly people to develop mood disorders. Because previous work showed that increasing the peripheral availability of tryptophan (TRP) to the brain holds antidepressant properties, this study evaluated whether TRP availability to the brain is increased during prolonged exercise in older men. METHODS: Nineteen males age 64 +/- 3 yr completed a treadmill exercise bout at an HR eliciting ~68% VO(2peak) for 60 min. Fasting blood was collected at rest, after 30 and 60 min of exercise, and at 90 min (after exercise). Branched-chain amino acids (BCAA), total and free TRP, prolactin, ammonia, nonesterified fatty acids, glucose, and lactate were measured. RESULTS: Changes in free TRP/BCAA ratio and prolactin were used as peripheral proxies of central serotonin synthesis rate and activity. The free TRP/BCAA ratio observed at baseline was increased by 102% after 1 h of exercise (P < 0.0001) and remained elevated after exercise (78% above baseline, P < 0.001). The free TRP portion in serum increased from 2.8 +/- 0.7 to 5.7 +/- 1.8 MUmol.L-1 after 1 h of exercise (P < 0.001) and was strongly correlated with plasma nonesterified fatty acid contents (r17 = 0.887, P < 0.0001, all time points). Serum prolactin was significantly elevated after 1 h of exercise (8.6 +/ 2.4 MUg.L-1, P < 0.001) and was positively correlated with free TRP/BCAA ratio (r16 = 0.48, P < 0.05, all time points). CONCLUSIONS: These results concur with previous observations in younger men and unveil that significant elevations in TRP availability to the brain are encountered during sustained exercise in older men. These results provide support to the hypothesis that increases in serotonin synthesis and activity might be involved in the antidepressant effect of exercise in the elderly. PMID- 22051570 TI - Daily step target to measure adherence to physical activity guidelines in children. AB - PURPOSE: There is a lack of robust evidence to support a daily step count target that equates to current physical activity guidelines in children and youth. This information would be useful to researchers and practitioners who are using pedometers to monitor physical activity. METHODS: Accelerometer and pedometer data collected on children and youth age 6-19 yr in the Canadian Health Measures Survey were used in this analysis (n = 1613). Correlation analyses of daily step counts and minutes of moderate-to-vigorous physical activity (MVPA) by age and sex were completed. The daily step count equivalent to 60 min of MVPA was derived using linear regression by age and sex. Cross-validation, including receiver operating curve analysis, was completed to compare the new cut points to one currently used as a proxy estimate of 60 min of daily MVPA (13,500 steps per day) as well as a range of possible step count targets between 8000 and 15,000 steps per day. RESULTS: Daily step counts were correlated with daily minutes of MVPA (r = 0.81, P < 0.0001). The step count equivalents to 60 min of MVPA ranged between 11,290 and 12,512 steps per day (R range = 0.59-0.74). A step count target of 12,000 steps per day resulted in closer population estimates of meeting the physical activity guideline (as measured as minutes of MVPA by accelerometer) as well as improved balance between sensitivity and specificity when compared with any cut point between 8000 and 15,000 steps per day, including the currently used daily step count target of 13,500 steps per day. CONCLUSIONS: We propose that 12,000 steps per day be used as a target to determine whether children and youth age 6-19 yr are meeting the current physical activity guideline of 60 min of daily MVPA. PMID- 22051571 TI - Isomaltulose improves glycemia and maintains run performance in type 1 diabetes. AB - PURPOSE: Individuals with type 1 diabetes mellitus (T1DM) are encouraged to reduce rapid-acting insulin and consume CHO to prevent hypoglycemia during or after exercise. However, research comparing the metabolic and performance effects of different CHO is limited. This study compared the alterations in metabolism and fuel oxidation in response to performance running after preexercise ingestion of isomaltulose or dextrose in T1DM. METHODS: After preliminary testing, on two occasions, seven T1DM individuals consumed 0.6 g.kg-1 body mass of either dextrose (DEX; glycemic index = 96) or isomaltulose (ISO; glycemic index = 32), 2 h before a discontinuous incremental run to 80% VO2peak on a motorized treadmill followed by a 10-min all-out performance test on a nonmotorized treadmill. Blood glucose (BG), acid-base, and cardiorespiratory parameters were measured 2 h before, during, and after both run tests. Data (mean +/- SEM) were analyzed using repeated-measures ANOVA. RESULTS: Preexercise BG area under the curve was lower under ISO in comparison with DEX (ISO = +4.0 +/- 0.3 mmol.L-1.h-1 vs DEX = +7.0 +/- 0.6 mmol.L-1.h-1, P < 0.01). Resting blood lactate concentrations and rate of CHO oxidation under ISO were greater than those elicited under DEX (P < 0.05). There were no metabolic or cardiorespiratory differences between conditions in response to submaximal exercise despite lower BG concentrations under ISO (P < 0.05). T1DM individuals completed the same distance at the same speed during the 10-min run test under both conditions (not significant). CONCLUSIONS: Consumption of isomaltulose alongside rapid-acting insulin reduction improves BG responses to exercise and produces a similar high-intensity run performance compared with dextrose in T1DM individuals. PMID- 22051574 TI - How has hospital consolidation affected the price and quality of hospital care? AB - During the 1990s, the hospital industry was transformed by mergers and acquisitions. This synthesis looks at why this rapid consolidation occurred and what impact it had on the price and quality for patients, and the cost of care for hospitals. Key findings include: Managed care was not a main driver of consolidation, but fear of managed care may have played a part. Other factors, including technological advances that reduced inpatient demand, and an antitrust environment that was receptive to consolidation contributed to consolidation. Research suggests hospital prices increased by 5 percent or more as a result of consolidation. When two hospitals merge, not only does the surviving hospital raise prices but so do its competitors. Evidence of the impact of consolidation on quality of care is limited and mixed, but the strongest studies show a reduction in quality. Hospital consolidation does modestly reduce the cost to hospitals of providing care. PMID- 22051572 TI - Exercise dose and insulin sensitivity: relevance for diabetes prevention. AB - PURPOSE: Exercise improves insulin resistance and is a first line for the prevention and treatment of type 2 diabetes. The extent, however, to which these responses are dose dependent is not known. The purpose of this study was to examine whether exercise dose was associated with improvements in insulin sensitivity after 4 months of exercise training in previously sedentary adults. METHODS: Fifty-five healthy volunteers participated in a 16-wk supervised endurance exercise intervention with a pre/postintervention design. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp, peak oxygen uptake by a graded exercise test, and body composition by dual-energy x-ray absorptiometry. The exercise intervention consisted of three to five sessions per week with a minimum of three sessions supervised. A ramped exercise prescription protocol was used to achieve 75% of peak HR for 45 min per session. Exercise dose, expressed as average kilocalories expended per week, was computed as the product of exercise intensity, duration and frequency. RESULTS: Improved insulin sensitivity was significantly related to exercise dose in a graded dose-response relationship. No evidence of threshold or maximal dose-response effect was observed. Age and gender did not influence this dose-response relationship. Exercise intensity was also significantly related to improvements in insulin sensitivity, whereas frequency was not. CONCLUSIONS: This study identifies a graded dose-response relationship between exercise dose and improvements in insulin sensitivity. The implication of this observation is of importance for the adaptation of exercise prescription in clinical situations. PMID- 22051575 TI - snoU6 and 5S RNAs are not reliable miRNA reference genes in neuronal differentiation. AB - Accurate profiling of microRNAs (miRNAs) is an essential step for understanding the functional significance of these small RNAs in both physiological and pathological processes. Quantitative real-time PCR (qPCR) has gained acceptance as a robust and reliable transcriptomic method to profile subtle changes in miRNA levels and requires reference genes for accurate normalization of gene expression. 5S and snoU6 RNAs are commonly used as reference genes in microRNA quantification. It is currently unknown if these small RNAs are stably expressed during neuronal differentiation. Panels of miRNAs have been suggested as alternative reference genes to 5S and snoU6 in various physiological contexts. To test the hypothesis that miRNAs may serve as stable references during neuronal differentiation, the expressions of eight miRNAs, 5S and snoU6 RNAs in five differentiating neuronal cell types were analyzed using qPCR. The stabilities of the expressions were evaluated using two complementary statistical approaches (geNorm and Normfinder). Expressions of 5S and snoU6 RNAs were stable under some but not all conditions of neuronal differentiation and thus are not suitable reference genes. In contrast, a combination of three miRNAs (miR-103, miR-106b and miR-26b) allowed accurate expression normalization across different models of neuronal differentiation. PMID- 22051576 TI - Dielectrophoretic tweezers as a platform for molecular force spectroscopy in a highly parallel format. AB - We demonstrated the application of a simple electrode geometry for dielectrophoresis (DEP) on colloidal probes as a form of molecular force spectroscopy in a highly parallel format. The electric field between parallel plates is perturbed with dielectric microstructures, generating uniform DEP forces on colloidal probes in the range of several hundred piconewtons across a macroscopic sample area. We determined the approximate crossover frequency between negative and positive DEP using electrodes without dielectric microstructures-a simplification over standard experimental methods involving quadrupoles or optical trapping. 2D and 3D simulations of the electric field distributions validated the experimental behavior of several of our DEP tweezers geometries and provided insight into potential improvements. We applied the DEP tweezers to the stretching of a short DNA oligomer and detected its extension using total-internal reflection fluorescence microscopy. The combination of a simple cell fabrication, a uniform distribution of high axial forces, and a facile optical detection of our DEP tweezers makes this form of molecular force spectroscopy ideal for highly parallel detection of stretching or unbinding kinetics of biomolecules. PMID- 22051577 TI - Are hot flashes associated with sleep disturbance during midlife? Results from the STRIDE cohort study. AB - OBJECTIVE: Sleep disturbance and hot flashes are common during menopause, but their association is not well understood. We sought to understand the associations among sleep disturbance and the frequency, bothersomeness, and interference of hot flashes in mid-life women. STUDY DESIGN: STRIDE is a study of women ages 40-65 years at varied menopausal stages. We examined the cross sectional associations of sleep disturbance with the frequency and bothersomeness of hot flashes, and interference of hot flashes with work, social, and leisure activities during the 2nd year of STRIDE. MAIN OUTCOME MEASURE: Self-reported sleep disturbance. RESULTS: Of the 623 women with complete data, 370 (59%) reported having hot flashes. Bivariate analyses showed that reporting hot flashes with bother, but not hot flashes alone, was associated with sleep disturbance (odds ratio [OR] [95% confidence interval (CI)]: 2.8 [2.0-4.0] and 1.3 [0.7-2.5], respectively). In multivariable models, women reporting bothersome hot flashes were more likely to report sleep disturbance (OR [95% CI]: 2.1 [1.4-3.2]) compared to women who reported no hot flashes. When the perceived interference of hot flashes with work, social activities, and leisure activities were included in the model, the relationships between bothersome hot flashes and sleep disturbance disappeared. CONCLUSIONS: Hot flashes are not associated with sleep disturbance, unless they are bothersome. Mid-life patients should routinely be queried about the bothersomeness of their hot flashes. PMID- 22051578 TI - Volatile components of the enzyme-ripened sufu, a Chinese traditional fermented product of soy bean. AB - In the present study, sufu, a soft cheese-like oriental fermented food, was prepared by ripening the salted-tofu cubes in Aspergillus oryzae-fermented soybean-rice koji at 37 degrees C for 16 days (16-day sufu). Sufu was further held at room temperature for another 30 days (46-day sufu). The volatile components of the non-fermented tofu cubes and the sufu products were identified and quantified by GC and GC-MS. A total of 70 volatile compounds including 20 aldehydes, 18 alcohols, 16 esters, 5 ketones, 5 acids and 6 other compounds were identified. Sufu products contained more volatile compounds than non-fermented tofu cubes qualitatively and quantitatively. After 16-days of ripening, fatty acid, aldehyde and ester were noted to be the dominant volatile fractions. In contrast, the 46-day sufu contained ester, and alcohol as the major volatile fractions. They comprise approximately 63.9% of the total volatile components. PMID- 22051579 TI - Regional cerebral oxygen saturation on hospital arrival is a potential novel predictor of neurological outcomes at hospital discharge in patients with out-of hospital cardiac arrest. AB - AIM: To investigate the association between regional brain oxygen saturation (rSO(2)) on hospital arrival and neurological outcomes at hospital discharge in patients with out-of-hospital cardiac arrest (OHCA). METHODS: A prospective cohort study was conducted, registering 179 patients with OHCA who were referred to Senri Critical Care Medical Centre between April 2009 and June 2010. Of these patients, 92 met the inclusion criteria. The primary end point was "neurological outcomes" at hospital discharge according to the "Utstein style" guidelines. RESULTS: The overall rate of good neurological outcome at hospital discharge was 14% (n=13). Sixty-one patients with rSO(2) <=25% showed poor neurological outcome in the receiver operating curve analysis (optimal cut-off point, 25%; sensitivity, 0.772; specificity, 1.000; positive predictive value, 1.000; area under the curve (AUC), 0.919; p<0.0001). The AUC for rSO(2) was greater than that for base excess (p=0.0461) or lactate (p=0.0128) measured on hospital arrival. Since rSO(2) >40% was previously collated with good neurological outcome after cardiovascular surgery, we categorised our patients into three groups in a post hoc analysis: patients with rSO(2) <=25% (n=61); patients with rSO(2) 26-40% (n=9) and patients with rSO(2) >40% (n=22). Patients with good neurological outcome were as follows: 0 (0%)/61 with rSO(2) <=25%; two (22.2%)/9 with rSO(2) 26-40% and 11 (50.0%)/22 with rSO(2) >40% (p<0.0001). CONCLUSION: rSO(2) on hospital arrival may help predict neurological outcomes at hospital discharge in patients with OHCA. PMID- 22051580 TI - The changes of brain water diffusion and blood flow on diffusion-weighted and perfusion-weighted imaging in a canine model of cardiac arrest. AB - OBJECTIVE: To study the changes of brain water diffusion and cerebral haemodynamics of cortical areas using magnetic resonance imaging (MRI) in canine models of cardiac arrest (CA) and restoration of spontaneous circulation (ROSC). The secondary study objective was to evaluate whether MRI can be used to observe haemodynamic disorders in brain microcirculation. METHODS: CA was induced in six beagle dogs using electrical stimulation followed by resuscitation to spontaneous circulation 3 min later. The dogs were scanned using MRI for echo planar, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) with injection of Gd-diethylene triamine pentaacetic acid (DTPA) prior to induction of CA and 3 days after ROSC. The arterial blood pressure, unilateral common carotid artery flow and intracranial microcirculation were recorded. RESULTS: All dogs successfully underwent electric-induced ventricular fibrillation which lasted 3 min and were resuscitated to maintain blood pressure stability. Serial MRI scans found that cerebral blood flow (RCBF) decreased in day 1 after ROSC and returned to baseline on day 3. Apparent diffusion coefficient (ADC), however, decreased on day 1 and remained lower than baseline on day 3, with 765.8+/-82.5*10(-6) mm(2) s(-1) on day 1 and 770.4+/-59.4*10(-6) mm(2) s(-1) on day 3 comparing to 855.8+/ 43.4*10(-6) mm(2) s(-1) on baseline. CONCLUSIONS: These data provide the evidence that early MRI can be used to observe acute haemodynamic disorders in brain microcirculation in a canine model of cardiac arrest. PMID- 22051581 TI - Violence towards those who care. PMID- 22051582 TI - The presence of fungi on contact electrical stimulation electrodes and ultrasound transducers in physiotherapy clinics. AB - OBJECTIVES: To evaluate the presence of fungi on contact electrodes and ultrasound transducers from physiotherapy clinics. DESIGN: Quantitative study conducted at the Laboratory of Microbiology and Immunology, Faculty of Health Sciences and Technology of Piaui - NOVAFAPI, Teresina, Brazil. SETTING: Sample collection was performed in 10 clinics (20 ultrasound transducers and 20 contact electrodes). MAIN OUTCOME MEASURES: Swabs were soaked with saline solution, inoculated in culture and incubated for filamentous fungi and yeast growth. RESULTS: Fourteen taxons were identified: Acremomium hyalinulum (Sacc.), Aspergillus terreus, Candida albicans, Cladosporium cladosporioides, Cladosporium elatum, Cladosporium oxysporum, Cladosporium sphaerospermum, Cladosphialophora bantiana, Curvularia clavata, Curvularia senegalensis, Fusarium oxysporum, Penicillium decumbens, Scopulariopsis candida and Sporothrix schenckii. Aspergillus terreus, Cladosporium oxysporum, Sporothrix shenckii and Candida albicans were found most often on contact electrodes, and Penicillium decumbens and Cladosporium cladosporioides were found most often on ultrasound transducers. CONCLUSION: Fungi were found on all of the contact electrodes and ultrasound transducers. Physiotherapy professionals need to improve the disinfection procedures for this equipment. PMID- 22051583 TI - Comparison of recognition tools for postoperative pulmonary complications following thoracotomy. AB - OBJECTIVES: To evaluate the recognition of postoperative pulmonary complications (PPC) following thoracotomy and lung resection using three PPC scoring tools. DESIGN: Prospective observational study. SETTING: Regional thoracic centre. PARTICIPANTS: One hundred and twenty-nine consecutive thoracotomy and lung resection patients (October 2007 and April 2008). MAIN OUTCOME MEASURES: PPC assessment was performed on a daily basis using three sets of criteria described by Brooks-Brunn, Gosselink et al. and Reeve et al.: the Brooks-Brunn Score (BBS), Gosselink Score (GS) and Melbourne Group Scale (MGS), respectively. The results were compared with treatment for PPC and clinical outcomes including mortality, postoperative length of stay and high dependency unit length of stay. RESULTS: PPC frequency was 13% (17/129) with the MGS, 6% (8/129) with the GS and 40% (51/129) with the BBS. The clinically observed incidence of treated (requiring antibiotic therapy or bronchoscopy) PPC was 12% (16/129). CONCLUSION: PPC treatment following thoracotomy is common. Of the three scoring tools, the MGS outperforms the BBS and the GS in terms of PPC recognition following thoracotomy and lung resection. Patients with a PPC-positive MGS score have a worse outcome as defined by mortality, high dependency unit length of stay and postoperative length of stay. The MGS is an easy-to-use multidisciplinary scoring tool, but further work is required into its use in minimally invasive surgery and in targeting high-risk groups for therapy. PMID- 22051584 TI - Pulmonary rehabilitation in Australia: a national survey. AB - OBJECTIVE: To determine the current structure and content of pulmonary rehabilitation programs in Australia. DESIGN: A cross sectional, observational design using a purpose designed anonymous written survey. SETTING AND PARTICIPANTS: The National database of Pulmonary Rehabilitation Programs maintained by the Australian Lung Foundation was used to identify all known programs in all states and territories of Australia (n=193). All pulmonary rehabilitation programs listed on the database were included. Respondents were health professionals who coordinated programs. RESULTS: The response rate was 83% (161/193). Programs were coordinated by physiotherapists (75/147, 51%) and/or nurses (49/147, 33%), were hospital based (97/147, 66%) and ran for 8 weeks or longer (95/147, 65%). Pre (145/147, 99%) and post (137/147, 93%) program assessment was undertaken using a variety of measures. The Six Minute Walk Test (138/147, 94%) was the most commonly used test of exercise capacity. Exercise training was included in 145 programs (99%). Most patients attended at least two supervised exercise sessions per week (106/147, 72%) and exercised for at least 20 minutes (135/147, 92%). Lower limb endurance, upper limb endurance, strength training, and stretching/flexibility exercises were the most commonly included modes of exercise. Intensity prescription for exercise training was variable. Many respondents (93/147, 63%) indicated that they perceived a gap between their clinical practice and current evidence. CONCLUSIONS: Pulmonary rehabilitation programs in Australia generally meet the broad recommendations for practice in terms of components, program length, assessment and exercise training. The prescription of exercise training intensity is an area requiring deeper exploration. PMID- 22051585 TI - A preliminary investigation into the effects of active interferential current therapy and placebo on pressure pain sensitivity: a random crossover placebo controlled study. AB - OBJECTIVE: (1) To determine the effect of active and placebo interferential current on muscle pain sensitivity using an experimental mechanically induced pain model. (2) To evaluate the predictive role of expectations, gender, baseline muscle pain sensitivity, and intervention order on placebo response. DESIGN: Randomized placebo controlled cross-over trial. SETTING: University research laboratory. PARTICIPANTS: Forty healthy volunteers (20 females, 20 males). INTERVENTIONS: Active interferential current, placebo (sham) interferential current, and no treatment/control were applied to the lumbar area on different days. MAIN OUTCOMES MEASURES: Pressure pain thresholds and placebo response. RESULTS: The two-way ANOVA with repeated measures analysis determined a significant interaction between condition and time (P=0.002). Pairwise comparisons found differences between active interferential and the control condition at 15 minutes into treatment (mean difference=0.890 kg/cm(2), 95% CI 0.023 to 1.757, P=0.043) and at 30 minutes into treatment (mean difference=0.910 kg/cm(2), 95% CI 0.078 to 1.742, P=0.028). The increase in pressure pain thresholds between the active interferential and the control condition (1.12 kg/cm(2)) was clinically meaningful. Logistic regression analysis showed that the condition sequence order was the only variable that predicted placebo response (odds ratio 9.7; P=0.028). If a subject started the sequence receiving placebo treatment first, the odds of responding to placebo would be approximately 10 times higher (i.e. 90% probability of being a placebo responder) than that of starting with an active treatment. CONCLUSIONS: Active interferential was more efficient than control condition in decreasing muscle pain sensitivity. Placebo interferential was not significantly different from control. Treatment sequence demonstrated a strong association with placebo response. These findings have implications for future research characterizing and identifying placebo responders in physiotherapy. PMID- 22051586 TI - Responsiveness of physical function outcomes following physiotherapy intervention for osteoarthritis of the knee: an outcome comparison study. AB - OBJECTIVE: To compare the responsiveness of two self-report measures and three physical performance measures of function following physiotherapy for osteoarthritis of the knee. SETTING: Single centre study in acute hospital setting. METHODS: Patients referred for physiotherapy with osteoarthritis of the knee were recruited. The Western Ontario and McMaster Universities (WOMAC), Lequesne Algofunctional Index (LAI), timed-up-and-go test (TUGT), timed-stand test (TST) and six-minute walk test (6MWT) were administered at first and final physiotherapy visits. Wilcoxon Signed Rank tests were used to determine the effect of physiotherapy on each outcome. Responsiveness was calculated using effect size, standardised response mean and a median-based measure of responsiveness due to some outlying data. RESULTS: Thirty-nine patients with a mean age of 65.3 (standard deviation 6.9) years were investigated before and after a course of exercise-based physiotherapy. There was a significant improvement in all outcomes except the WOMAC scores. All measures demonstrated small effect sizes for all statistics (<0.50), except the 6MWT which was in the moderate range for one of the indices (standardised response mean 0.54). The LAI was more responsive than the WOMAC total score and the WOMAC physical function subscale for all responsiveness statistics, whilst the 6MWT was more responsive than the TST and the TUGT. The median-based effect size index produced the smallest effect sizes for all measures (0.1 to 0.43). CONCLUSION: These results can be used to guide decision making about which physical function outcome measures should be used to evaluate effectiveness of rehabilitation of people with osteoarthritis of the knee at group level in a clinical setting. PMID- 22051587 TI - Calculating effect size for continuous variables: D537--a robust, quantile-based approach. AB - The calculation of effect size is an important step in measuring the potential real-life significance of the effect of an intervention. In the case of continuous data, Cohen's d is frequently used. This scales the difference between the means of two groups, or the mean difference between pairs of measurements, by dividing by the standard deviation. However, outlying values, especially in small studies, can influence the size of d. This article presents D537, a robust formula for d that is based on rank statistics. The median is used as a measure of difference, while the scaling factor is the range between the 30th and 70th percentiles of the distribution; a range that is equal to one standard deviation when the data are normally distributed. When data are normally distributed, the value of D537 is equal to that of Cohen's d. As D537 is based on the 30th, 50th and 70th percentiles, it is robust to outliers. PMID- 22051588 TI - Physiotherapy students' experience, confidence and attitudes on the causes and management of violent and aggressive behaviour. AB - OBJECTIVES: Healthcare professionals are at risk of experiencing violent and aggressive behaviour from patients. This is most notable in those with least experience, such as students, yet little reported research has considered the experiences of physiotherapy students. The aims of this study were to: (1) explore the incidence and nature of violent and aggressive behaviour experienced by physiotherapy students; and (2) consider the attitudes and confidence of the students in dealing with such behaviour. DESIGN: Retrospective survey. SETTING: A university in the Midlands region of the UK. PARTICIPANTS: Sixty-four final year physiotherapy students. MAIN OUTCOME MEASURES: The Management of Aggression and Violence Attitude Scale and an additional survey. RESULTS: Over half (33/64, 52%) of the respondents had experienced at least one incident of violent and aggressive behaviour on a clinical placement. The overwhelming majority of victims (60/64, 94%) did not feel adequately confident to deal with such situations. However, no incidents were officially reported to the university. Both victims and non-victims agreed broadly with the internal model of the causes of aggression and violence, but significantly (P=0.02) more victims did not associate the violent and aggressive behaviour with the responsibility of the patient to control their feelings. CONCLUSIONS: Many physiotherapy students experience at least one incident of violent and aggressive behaviour whilst on a clinical placement. Training in the recognition and management of violent and aggressive behaviour would be a beneficial addition to the curricula of physiotherapy programmes. Further larger scale research is warranted. PMID- 22051589 TI - Penetration and spread of interferential current in cutaneous, subcutaneous and muscle tissues. AB - OBJECTIVES: To investigate the penetration depth of interferential current (IFC) through soft tissue and the area over which it spreads during clinical application. DESIGN: A laboratory-based study of healthy participants. SETTING: A university research laboratory. PARTICIPANTS: Twelve healthy subjects. INTERVENTIONS: Premodulated IFC at 90 Hz and 'true' IFC at frequencies of 4, 40 and 90 Hz were applied via four electrodes, in a quadrant setting, to the distal medial thigh of each participant on separate occasions. MAIN OUTCOME MEASURE: Voltage induced by tested currents was measured at three locations (middle of the four electrodes, in line with one circuit and outside the four electrodes) and three depths (skin, subcutaneous and muscle tissues) using three Teflon-coated needle electrodes connected to a Cambridge Electronic Design data acquisition system. RESULTS: All voltages were greater at all depths and locations compared with baseline (P<0.001): premodulated IFC [mean difference 0.112, 95% confidence interval (CI) 0.065 to 0.160], 4 Hz (mean difference 0.168, 95% CI 0.106 to 0.229), 40 Hz (mean difference 0.165, 95% CI 0.107 to 0.223) and 90 Hz (mean difference 0.162, 95% CI 0.102 to 0.221). Voltages decreased with depth. Lower voltages of all currents were recorded in the middle of the four electrodes, with the highest voltage for 'true' IFC being recorded outside the four electrodes (mean difference 0.04, 95% CI 0.01 to 0.029; P=0.011). The premodulated IFC had the highest voltage in line with one circuit. CONCLUSIONS: IFC passed through soft tissues, with the highest voltages recorded in superficial tissue and the lowest voltages recorded in muscle. For 'true' IFC, the current spread outside the electrodes at higher voltages compared with the intersection of the four electrodes. The premodulated IFC had the highest voltage in line with one circuit. In terms of higher recorded voltages, 'true' IFCs were more efficient than the premodulated IFC when targeting deeper tissues. However, further studies with larger samples are required to confirm the results of this study. PMID- 22051590 TI - A national survey of the physiotherapy management of patients following first time patellar dislocation. AB - OBJECTIVES: The purpose of this study was to determine how musculoskeletal physiotherapists in acute National Health Service (NHS) hospitals manage patients following a first time patellar dislocation. DESIGN: National survey study. SETTING: All NHS acute hospitals with an accident and emergency and/or an orthopaedic department were surveyed. PARTICIPANTS: 306 institutions were surveyed. INTERVENTIONS: Each institution was sent a 14 question self administered questionnaire pertaining to the assessment, treatment, evaluation and outcome of patients following a first time patellar dislocation. After 3 weeks, all non-respondents were sent a reminder letter. After a further 3 weeks, those who had not responded by this time were sent a final reminder and copy of the questionnaire. RESULTS: The survey response rate was 59%. The respondents indicated that first-time patellar dislocation was not a common musculoskeletal disorder managed by NHS physiotherapists, constituting an average of 2% of caseloads. The results suggested that physiotherapists most commonly assess for reduced quadriceps or VMO capacity, gait, patellar tracking and glide, and knee effusion when examining patients following a first-time patellar dislocation. The most common treatments adopted are reassurance, behaviour modification followed by proprioceptive, knee mobility, quadriceps and specific VMO exercises. CONCLUSIONS: Generic lower limb assessment and treatment strategies are widely used to manage this patient group. Given the previous paucity in this literature, further study is now recommended to assess the efficacy of these interventions to provide UK physiotherapists with an evidence-base to justify their management strategies. PMID- 22051591 TI - Impact of the Accreditation of Clinical Educators scheme: reflections from one higher education institution. AB - OBJECTIVE: To provide a critically reflective account of clinical educators' experiences of the Accreditation of Clinical Educators (ACE) scheme, launched by the Chartered Society of Physiotherapy in 2004, and its impact on practice. DESIGN: A qualitative methodology with three elements: focus group interviews during the accreditation process, and completion of a questionnaire at its conclusion and 6 months following completion. All data were transcribed and analysed using the constant comparative method. PARTICIPANTS: Seventeen participants provided initial feedback through focus group interviews. Thirteen participants completed all three phases of the inquiry. The sample was purposive. RESULTS: Three main themes emerged: getting to grips with reflection: a benefit for CPD; the relationship between professional recognition, competence and confidence; and perceived impact within the educators' scope of influence. CONCLUSIONS: This small-scale study of the outcomes of clinical educators' engagement with the ACE process suggests that it contributes to their personal and professional development by helping them to gain experience of portfolio building and reflective writing, and increasing confidence in their own competence through providing acknowledgment of having achieved a recognised standard. The ACE scheme appears to impact positively on clinical educators' approaches to supporting students on clinical placement. However, positive effects also extend to colleagues and clients. PMID- 22051592 TI - Respiratory physiotherapy: towards a clearer definition of terminology. AB - Interventions used in clinical practice and research need to be described in sufficient detail to permit accurate replication. Since words and phrases can change their meaning over time, it is important that authors choose their words carefully and define anything which might be ambiguous. 'Breathing exercises' is a phrase which covers a multitude of therapeutic approaches. Recent randomised controlled trials have established the value of teaching patients with asthma to retrain their breathing. However, the descriptions of the breathing interventions are generally inadequate. This problem stems partly from a degree of confusion surrounding terms such as 'diaphragmatic breathing' which has been variously interpreted. A more structured approach to reporting such interventions is proposed. This approach will help to avoid confusion, and will permit the transfer of those interventions found to be effective in research trials into routine clinical practice. PMID- 22051593 TI - Familiarisation with lower limb strength testing in middle-aged women with osteoarthritis of the knee. PMID- 22051594 TI - Adolescent hip pain: the needle in the haystack. A case report. PMID- 22051595 TI - Traumatic pneumothorax sustained via fine-wire electromyography insertion at the shoulder. PMID- 22051596 TI - Synthesis of ruthenium(II) complexes of tetradentate bis(N pyridylimidazolylidenyl)methane and their reactivities towards N- donors. AB - A family of hexa-coordinated ruthenium(II) complexes of bis(N pyridylimidazolylidenyl)methane (L) were prepared and structurally characterized. Carbene transfer reactions of [Ru(p-cymene)Cl(2)](2), [Ru(CO)(2)Cl(2)](n) and RuHCl(CO)(PPh(3))(3) with silver-NHC complexes in situ generated from [H(2)L](PF(6))(2) and Ag(2)O afforded [RuL(CH(3)CN)(2)](PF(6))(2) (1), [Ru(2)L(p cymene)(2)Cl(2)](PF(6))(2) (2), [RuL(CO)(2)](PF(6))(2) (3) and [RuL(PPh(3))(2)](PF(6))(2) (4), respectively. The reactions of 1 towards several N- and P-donors were studied. The treatment of 1 with 1,10-phenanthroline resulted in the substitution of one pyridine and one acetonitrile molecule affording [RuL(phen)(CH(3)CN)](PF(6))(2) (5) as a mixture of two isomers. Reaction of 1,2-bis(diphenylphosphino)ethane (dppe) and 1 gave [RuL(dppe)(CH(3)CN)(2)](PF(6))(2) (7), in which two pyridines were substituted by a dppe ligand trans to two NHC groups. In contrast, reactions of 1 with ethane 1,2-diamine, propane-1,3-diamine and 3,5-dimethyl-1H-pyrazole led to the substitution of acetonitrile and subsequent N-H addition of the C=N bond of the coordinated acetonitrile yielding [RuL(ethane-1,2-diamine)(N-(2 aminoethyl)acetimidamide)](PF(6))(2) (8), [RuL(propane-1,3-diamine)(N-(3 aminopropyl)acetimidamide)](PF(6))(2) (9) and RuL(1-(3,5-dimethyl-1H-pyrazol-1 yl)ethanimine)(CH(3)CN)](PF(6))(2) (10), respectively. PMID- 22051597 TI - Rapid residue analysis of fluoroquinolones in raw bovine milk by online solid phase extraction followed by liquid chromatography coupled to tandem mass spectrometry. AB - Online solid phase extraction followed by liquid chromatography coupled to tandem mass spectrometry was used for the determination of 15 fluoroquinolones and one quinolone antibiotic in raw bovine and skimmed commercial milk. Milk samples were partially deproteinized and defatted by 15 min centrifugation and then subjected to online solid phase extraction. Chromatographic separation was achieved in less than 15 min. Identification and quantification of the compounds of interest were performed by selected reaction monitoring, using an electrospray ionization source. Relative recoveries were calculated for raw milk (at 0.5, 1 and 1.5 times the MRL, or assuming 30 ng/mL for non permitted compounds) and skimmed milk (at 30 ng/mL) and ranged between 65% and 123% (raw milk) or 78% and 109% (skimmed milk). Matrix interferences were also assessed and yielded significant suppression and enhancement effects, which, at the time of quantification, were corrected by the use of six isotopically labeled standards. Quality parameters of the method were established, and limits of detection of selected antibiotics in raw milk ranged from 0.01 to 1.93 ng/mL, while in skimmed milk from 0.03 to 4.23 ng/mL. The validation of the method has been carried out according to the requirements set by the 2002/657/EC regulation. Finally, the applicability of the method was tested by analysing 28 milk samples. PMID- 22051598 TI - AAV vector biology in primates: finding the missing link? PMID- 22051601 TI - Personalized cell transfer immunotherapy for B-cell malignancies and solid cancers. PMID- 22051602 TI - An intravenous stimulus package for oncolytic virotherapy. PMID- 22051605 TI - Novel photocatalytic antibacterial activity of TiO2 microspheres exposing 100% reactive {111} facets. AB - TiO(2) microspheres constructed by well-crystallized faceted nanorods with high aspect ratios expose 100% photocatalytic reactive {111} facets on the spherical surface. The microspheres demonstrated excellent photocatalytic antibacterial activity towards Staphylococcus aureus due to effective suppression of photoinduced electron-hole pair recombination and active TiO(2)@OH core-shell structure. PMID- 22051606 TI - Persistence: mechanisms for triggering and enhancing phenotypic variability. AB - When microorganisms are exposed to lethal agents, the initial exponential decay in survival is typically followed by a slower decrease. This tailing of the survival curve is due to persister cells that have differentiated into phenotypes with reduced sensitivity to the lethal agent. We review the environmental factors that have been shown to trigger such differentiation processes, as well as the network motifs that enable the co-existence of persistent and nonpersistent cells within genetically uniform populations. Threshold amplification of noise and bi stability from positive feedback emerge as key motifs underlying persistence. PMID- 22051604 TI - Manipulation or capitulation: virus interactions with autophagy. AB - Autophagy is a homeostatic process that functions to balance cellular metabolism and promote cell survival during stressful conditions by delivering cytoplasmic components for lysosomal degradation and subsequent recycling. During viral infection, autophagy can act as a surveillance mechanism that delivers viral antigens to the endosomal/lysosomal compartments that are enriched in immune sensors. Additionally, activated immune sensors can signal to activate autophagy. To evade this antiviral activity, many viruses elaborate functions to block the autophagy pathway at a variety of steps. Alternatively, some viruses actively subvert autophagy for their own benefit. Manipulated autophagy has been proposed to facilitate nearly every stage of the viral lifecycle in direct and indirect ways. In this review, we synthesize the extensive literature on virus-autophagy interactions, emphasizing the role of autophagy in antiviral immunity and the mechanisms by which viruses subvert autophagy for their own benefit. PMID- 22051607 TI - WWP1: a versatile ubiquitin E3 ligase in signaling and diseases. AB - WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is a multifunction protein containing an N-terminal C2 domain, four tandem WW domains for substrate binding, and a C-terminal catalytic HECT domain for ubiquitin transferring. WWP1 has been suggested to function as the E3 ligase for several PY motif-containing proteins, such as Smad2, KLF5, p63, ErbB4/HER4, RUNX2, JunB, RNF11, SPG20, and Gag, as well as several non-PY motif containing proteins, such as TbetaR1, Smad4, KLF2, and EPS15. WWP1 regulates a variety of cellular biological processes including protein trafficking and degradation, signaling, transcription, and viral budding. WWP1 has been implicated in several diseases, such as cancers, infectious diseases, neurological diseases, and aging. In this review article, we extensively summarize the current knowledge of WWP1 with special emphasis on the roles and action of mechanism of WWP1 in signaling and human diseases. PMID- 22051608 TI - When the brain decides: a familiarity-based approach to the recognition heuristic as evidenced by event-related brain potentials. AB - Humans can make fast and highly efficient decisions by using simple heuristics that are assumed to exploit basic cognitive functions. In the study reported here, we used event-related potentials (ERPs) to disclose the psychological mechanisms underlying one of the most frugal decision rules, namely, the recognition heuristic. According to this heuristic, whenever two objects have to be ranked by a specific criterion and only one object is recognized, the recognized object is ranked higher than the unrecognized object. Using a standard recognition-heuristic paradigm, we predicted participants' decisions by analyzing an ERP correlate of familiarity-based recognition occurring 300 to 450 ms after stimulus onset. The measure remained a significant predictor even when later ERP correlates were taken into account. These findings are evidence for the thesis that simple heuristics exploit basic cognitive processes. Specifically, the findings show that familiarity--that is, recognition in the absence of recollection--contributes to decisions made on the basis of such heuristics. PMID- 22051609 TI - Familial versus sporadic amyotrophic lateral sclerosis--a false dichotomy? PMID- 22051610 TI - Filtering microfluidic bubble trains at a symmetric junction. AB - We report how a nominally symmetric microfluidic junction can be used to sort all bubbles of an incoming train exclusively into one of its arms. The existence of this "filter" regime is unexpected, given that the junction is symmetric. We analyze this behavior by quantifying how bubbles modulate the hydrodynamic resistance in microchannels and show how speeding up a bubble train whilst preserving its spatial periodicity can lead to filtering at a nominally symmetric junction. We further show how such an asymmetric traffic of bubble trains can be triggered in symmetric geometries by identifying conditions wherein the resistance to flow decreases with an increase in the number of bubbles in the microchannel and derive an exact criterion to predict the same. PMID- 22051611 TI - The effects of galanin on dorsal root ganglion neurons with high glucose treatment in vitro. AB - The exposure of neurons to high glucose concentrations is considered a determinant of diabetic neuropathy. The extracellular high concentration of glucose can cause neuronal cellular damage. Galanin (Gal) not only plays a role in processing of sensory information but also participates in energy homeostasis and glucoregulation. However, the effects of Gal on dorsal root ganglion (DRG) neurons with high glucose are not clear. Using an in vitro model of high glucose treated DRG neurons in culture, the effects of Gal on intracellular reactive oxygen species (ROS) expression, cell viability, apoptosis, expression of Gal and its receptors (GalR1 and GalR2) of DRG neurons were investigated. Neurons were dissociated from embryonic day 15 (E15) rat DRG and cultured for 48 h and then maintained in serum-free neurobasal medium containing high glucose (45 mmol/L) or normal glucose (25 mmol/L) for 24h. Mannitol (20 mmol/L) was also used to create a high osmotic pressure mimicking the high glucose condition. The results showed that high glucose caused a rapid increasing of intracellular ROS, decreases of cell viability, and upregulation of Gal and its mRNA. Exogenous Gal (1 MUmol/L) inhibited the above effects caused by high glucose. Interestingly, high glucose caused downregulation of GalR1 and its mRNA and administration of exogenous Gal could further decrease their expression, whereas expression of GalR2 and its mRNA was not affected at different experimental conditions. The results of the present study indicate for the first time that Gal and its receptor system are involved in high glucose-induced DRG neuronal injury. The contribution of exogenous Gal on neuroprotection appears to be quite significant. These results provide rationale and experimental evidence for development and further studies of Gal on therapeutic strategy for improving diabetic neuropathy. PMID- 22051612 TI - Creatine reduces oxidative stress markers but does not protect against seizure susceptibility after severe traumatic brain injury. AB - Achievements made over the last years have highlighted the important role of creatine in health and disease. However, its effects on hyperexcitable circuit and oxidative damage induced by traumatic brain injury (TBI) are not well understood. In the present study we revealed that severe TBI elicited by fluid percussion brain injury induced oxidative damage characterized by protein carbonylation, thiobarbituric acid reactive species (TBARS) increase and Na(+),K(+)-ATPase activity inhibition 4 and 8 days after neuronal injury. Statistical analysis showed that after TBI creatine supplementation (300 mg/kg, p.o.) decreased the levels of protein carbonyl and TBARS but did not protect against TBI-induced Na(+),K(+)-ATPase activity inhibition. Electroencephalography (EEG) analysis revealed that the injection of a subconvulsant dose of PTZ (35 mg/kg, i.p.), 4 but not 8 days after neuronal injury, decreased latency for the first clonic seizures and increased the time of spent generalized tonic-clonic seizures compared with the sham group. In addition, creatine supplementation had no effect on convulsive parameters induced by a subconvulsant dose of PTZ. Current experiments provide evidence that lipid and protein oxidation represents a separate pathway in the early post-traumatic seizures susceptibility. Furthermore, the lack of consistent anticonvulsant effect exerted by creatine in this early phase suggests that its apparent antioxidant effect does not protect against excitatory input generation induced by TBI. PMID- 22051613 TI - [Superficial mycoses in the city of Valparaiso, Chile: period 2007-2009]. AB - INTRODUCTION: Superficial mycoses are infections of the keratinous tissue caused by dermatophytes, yeasts and environmental fungi. OBJECTIVES: To identify the species of dermatophytes, yeasts and environmental fungi that cause superficial mycosis and analyze their differences by sex, age and location of the lesion, in patients from the region of Valparaiso, during 2007-2009. MATERIALS AND METHODS: 1004 patients diagnosed with superficial mycoses were studied. All ages and both genera were included. The study was done using direct microscopic examination with 20% KOH and culture of the lesions. Fungi identification was mainly morphophysiological. RESULTS: Of the 1004 patients studied, 609 were women and 87.7% was 15 years old or younger. Toenail onychomycosis was the most frequent lesion (58.1%), followed by tinea pedis and interdigitalis (16.3%). In patients younger than 8 years old, tinea capitis by Microsporum canis was the most common mycoses. Among dermatophytes, Trichophyton rubrum (78.9%) predominated in most locations, followed by Trichophyton mentagrophytes (14.9%) and M. canis (5.4%). Candida spp. (95.4%) prevailed among the yeasts causing onychomycosis. There were 27 cases of toenail onychomycosis caused by environmental fungi, mainly Fusarium. CONCLUSIONS: Our results are consistent with national and international data, where T. rubrum is the predominant agent of dermatomycoses. We report the emergency of agents not described in Chile or Latin America in these infections. PMID- 22051614 TI - [In vitro andulafungin susceptibility of 100 of Candida strains obtained previously to the introduction of this echinocandin in Chile]. AB - Fungi, particularly yeasts, have become important opportunistic pathogens that can be resistant to antifungal agents or develop resistance. To address this problem, new molecules such as echinocandins, have been developed. Susceptibility to anidulafungin was studied in yeasts isolated previous to the introduction of this drug in Chile. One hundred strains of different yeast species isolated from invasive fungal infections during 2007 and 2008 were studied. Susceptibility testing of anidulafungin was performed by broth microdilution according to CLSI. All strains were susceptible to anidulafungin. MIC50 and MIC90 were 0.125 ug/mL and 1 ug/mL, respectively. Compared to other yeasts, C. parapsilosis showed a slight increase in the MICs for anidulafungin (MIC50, 1 ug/mL, MIC90, 2 ug/mL), but remained within the susceptible range. Both, fluconazole resistant (8) and dose dependent susceptible strains (16) were susceptible to anidulafungin. In vitro, this echinocandin appears to be an effective therapeutic alternative. PMID- 22051615 TI - [Declaration of Punta del Este concerning antimicrobial resistance in Latin America]. PMID- 22051617 TI - [Kawasaki disease: a clinical serie]. AB - INTRODUCTION: Kawasaki disease (KD) is a serious disease in children due to its potential complications and sequelae if not promptly and adequately managed. OBJECTIVES: To describe clinical and epidemiological characteristics of children hospitalized due to KD at a tertiary care center and identify risk factors for poor outcome. PATIENTS AND METHODS: Retrospective and descriptive study of 32 medical records of patients hospitalized with diagnosis of KD at a tertiary care center of Santiago, Chile between February 1999 and May 2007. RESULTS: The annual frequency was of 5 cases, mainly boys and during spring. The median age at diagnosis was 1.5 years and 87.5% of the children were younger than 5 years. Typical presentation prevailed in all ages (68,7%). Coronary artery affection, including dilatation or aneurisms, occurred in 21.9% of the cases, with aneurysms in 3 cases. All patients were treated with aspirin and intravenous immunoglobulin (IVIG); 4 patients required a second dose. No deaths were reported. The identified risk factors for poor outcome were age older than 5 years and hypoalbuminemia. CONCLUSIONS: KD is an infrequent disease that mainly occurs in children younger than 5 years and with a typical presentation. There are risk factors associated with poor outcome. PMID- 22051618 TI - [Diagnostic methods in candidemia: a systematic review of literature with meta analysis]. AB - Candidemia is a disease with high morbidity and mortality especially in critical care patients. Early diagnosis enables early treatment. OBJECTIVES: To conduct a systematic review of the literature in order to establish the best laboratory tests for the diagnosis of candidemia in critical patients. MATERIALS AND METHODS: We conducted a systematic review of available literature in PubMed. Serological studies were subjected to meta-analysis in metadisk-Beta 1.1.1. RESULTS: 4 studies of 1286 reviewed were included. Three were about serological tests and one about molecular testing (RT-PCR). The sensitivity and specificity for RT-PCR, antibody testing and antigen and antibody tests were 87% and 100%, 47.5% and 82.6%, 96% and 81%, respectively. Diagnostic Odds Ratio of antigenemia was 1.51 (95% CI = 0,032-70,964, p = 0.001). CONCLUSIONS: RT-PCR has better diagnostic performance, measuring antigenemia plus antibodies improves sensitivity, specificity, LR + and LR-- . There is insufficient evidence to support this. PMID- 22051619 TI - [Weeksella virosa]. PMID- 22051620 TI - [Prevalence of ocular lesions in children seropositive to Toxocara canis]. AB - Intraocular invasion by Toxocara canis is one of the most commonly recognized etiologies of uveitis and blindness in children. In order to estimate the prevalence of ocular lesions caused by toxocariasis in a pediatric referral hospital, we conducted a retrospective analysis of clinical charts of all children seropositive to Toxocara canis, who also had an eye exam between the years 2005 and 2009 at the Calvo Mackenna Children's Hospital in Santiago, Chile. We identified 175 children [mean age 6 years (range 0.66-15)] seropositive to Toxocara canis, who had dilated eye exam. Only one child [(0.57%); 95% CI, -0.55 1.69] had ophthalmoscopic findings compatible with Toxocara canis infection. The patient also suffered from decreased vision of the affected eye. The information gained from this study may be of useful for the implementation of algorithms for the ophthalmological examination of children seropositive to Toxocara canis in public hospitals in Chile. PMID- 22051621 TI - [Ectoparasitosis of clinical importance in Chile]. AB - Several parasitic diseases affect the skin and appendages in humans, the most common are head lice and scabies. Both diseases have worldwide distribution with geographical variations. In Chile, the reported prevalence of head lice is 20-25% and of scabies 1-5%. Other ectoparasites include fleas and mite, causing transient parasitosis related to human and animal contact. These parasites are associated with various factors such as poor personal hygiene, promiscuity, long hair, crowding, and sharing of combs, among others. Various effective pharmacological therapies are available, which base on several active compounds. Important therapeutic options include topical treatments with pyrethroids, lindane, crotamiton, and malathion as well as oral medications such as ivermectin, which is used in case of drug intolerance, poor treatment response, infections with multiple parasites or concomitant bacterial infections. For some drugs, resistance has been reported in patients received multiple dosis. PMID- 22051622 TI - [Diagnosis and treatment of opportunistic infections in HIV/AIDS adult patients]. AB - The following guidelines for the diagnosis and treatment of opportunistic infections (OI) in adult HIV/AIDS patients represent the first approach to standardize the management of this patient group in Chile. The guidelines are based on scientific evidence. They intend to serve as a practical and easy-to-use tool for physicians during the process of selecting appropriate diagnostic tests and effective treatments for their patients. They also include the local experience in Chile related to OI in HIV/AIDS patients. Regular up-dates to include new scientific knowledge are proposed. PMID- 22051623 TI - [Antiretroviral resistance in human immunodeficiency virus infection]. AB - Resistance to anti-retroviral therapy is one of the main problems in the favorable outcome of treatment in HIV patients, as well as toxicity and adherence to treatment. Resistance has increased in recent years, and it is evaluated through genotyping and phenotypic tests. Information provided by these studies is crucial when deciding the most appropriate treatment. However, genotype interpretation is complex and subject to frequent change, because of the incorporation of new drugs and the appearance of new resistance patterns. This review aims ,understanding the fundamental concepts of antiretroviral resistance (ARV), which examines the general principles, mechanisms and patterns of resistance, both for the traditional family of anti-retrovirals, as well as for the most recently licensed drugs. PMID- 22051624 TI - [Acute gastroenteritis caused by a Vibrio cholerae non-O1, non-O139 strain harboring a genetic region homologous to the VpaI-7 pathogenicity island]. AB - Pathogenic Vibrio cholerae isolates, the etiologic agents of cholera, generally express one of two O antigens (O1 or O139). Most environmental isolates are nonpathogenic and are referred to as "non-O1, non-O139". However some V. cholerae non-O1, non-O139 strains are clearly pathogenic and have caused outbreaks or sporadic cases of gastroenteritis and extraintestinal infections in humans. We report a case of acute gastroenteritis by a V. cholerae non-O1, non-O139 harboring a genetic region homologous to a segment of the VpaI-7 V. parahaemolyticus pathogenicity island. PMID- 22051625 TI - [Breast implant infection by Mycobacterium fortuitum in a patient with systemic lupus erythematosus]. AB - In recent decades there has been an increase in the number of breast implants for reconstruction and cosmetic purposes. Infection is a severe complication mostly caused by Staphylococcus aureus or coagulase-negative staphylococci. Mycobacteria are an infrequent cause of infection in this type of surgery. We describe a case of Mycobacterium fortuitum infection in a patient with lupus, subjected to a prosthetic replacement. These patients are more prone to unusual opportunistic infections. Treatment always requires both removal of prosthetic material and antibiotic therapy. PMID- 22051626 TI - [Elimination of juvenile stages of Ascaris lumbricoides (Linnaeus, 1758) by mouth. Report of a case and some epidemiological considerations]. AB - Ascariosis is a parasitic disease caused by Ascaris lumbricoides, a large geohelmint endemic in our country. At present, ascariosis is a rare infection in Chile. We present a case of an adult, resident of the Villa Alemana municipality, Valparaiso Region, who spontaneously expelled two juvenile nematodes by mouth. We review the manifestations produced by the larval and adult stages of this parasite including their diagnosis, treatment, and epidemiological considerations. PMID- 22051627 TI - [Dr. Pedro Moran, the medical school of 1833, and the battle of Rancagua]. AB - With the foundation of the Medical School of 1833, the figure of Pedro Moran, the first professor of anatomy, physiology and hygiene, stands out. Diverse comments of his acts are recounted, some praising him and others revealing his concealment during the heat of the battle. His humble origins, competence and perseverance in the fulfillment of the teaching duties are extolled. PMID- 22051628 TI - Diffuse hepatic calcification following ischemic insult in the setting of impaired renal function. PMID- 22051629 TI - Medical malpractice: impact of the crisis and effect of state tort reforms. AB - As a result of rapidly rising medical malpractice insurance premiums, reduced availability of coverage, and financially distressed liability insurers, many states have passed tort reforms. This synthesis examines the medical malpractice ""crisis"" and the effect of state tort reforms. Evidence shows that caps on non economic damages reduce the average size of malpractice awards by 20 to 30 percent and have a modest impact on malpractice insurance premium growth There is also evidence that the most severely injured patients are disproportionately affected by caps, however. Other state reforms such as changes to joint-and several liability, statutes of limitations, or attorney contingency fees have had little impact. Studies do not support the notion that overall physician supply has decreased, nor that there is a relationship between malpractice cost and physician supply. There is ""good evidence"" that doctors ""often"" engage in defensive medicine, ordering referrals, medications and tests to protect themselves from liability, but the impact of this practice is difficult to quantify. PMID- 22051630 TI - Hydrolytic behaviour and chloride ion binding capability of [Ru(eta6-p cym)(H2O)3]2+: a solution equilibrium study. AB - Hydrolysis of an organometallic cation, [Ru(eta(6)-p-cym)(H(2)O)(3)](2+) (p-cym = 1-isopropyl-4-methylbenzene), in the presence of 0.20 M KNO(3) or KCl as supporting electrolyte was studied in detail with the combined use of pH potentiometry, (1)H-NMR, UV-VIS and ESI-TOF-MS. Stoichiometry and stability constants of chlorido, hydroxido and mixed chlorido-hydroxido complexes formed in aqueous solution have been determined. At pH < 4.0 where hydrolysis of [Ru(eta(6) p-cym)(H(2)O)(3)](2+) is negligible with increasing chloride ion concentration two chlorido complexes, [Ru(eta(6)-p-cym)(H(2)O)(2)Cl](+) and [{Ru(eta(6)-p cym)}(2)(MU(2)-Cl)(3)](+), are detectable. At pH > 5.0, in chloride ion free samples the exclusive formation of [{Ru(eta(6)-p-cym)}(2)(MU(2)-OH)(3)](+) is found. However, if chloride ion is present (in the range 0-3.50 M) novel mixed chlorido-hydroxido species, [{Ru(eta(6)-p-cym)}(2)(MU(2)-OH)(2)(MU(2)-Cl)](+) and [{Ru(eta(6)-p-cym)}(2)(MU(2)-OH)(MU(2)-Cl)(2)](+) can also be identified at pH > 4.0. The results obtained in this study may help in rationalizing the solution behaviour of half-sandwich [Ru(eta(6)-p-cym)(XY)Z] type complexes which, after dissociation of both the monodentate Z and the chelating XY, are capable of yielding the free aqua species [Ru(eta(6)-p-cym)(H(2)O)(3)](2+). Our results demonstrate that different chloride ion concentrations can influence the speciation in the acidic pH range but at biologically relevant conditions (pH = 7.4, c(Cl(-)) = 0.16 M) and at c(M) = 1 MUM [{Ru(eta(6)-p-cym)}(2)(MU(2) OH)(3)](+) is predominant in the absence of any coordinating ligands. PMID- 22051631 TI - Molecular cloning, heterologous expression and functional characterization of a novel translationally-controlled tumor protein (TCTP) family member from Loxosceles intermedia (brown spider) venom. AB - Envenoming with brown spiders (Loxosceles genus) is common throughout the world. Cutaneous symptoms following spider bite accidents include dermonecrosis, erythema, itching and pain. In some cases, accidents can cause hypersensibility or even allergic reactions. These responses could be associated with histaminergic events, such as an increase in vascular permeability and vasodilatation. A protein that may be related to the effects of spider venom was identified from a previously obtained cDNA library of the L. intermedia venom gland. The amino acid sequence of this protein is homologous to proteins from the TCTP (translationally-controlled tumor protein) family, which are extracellular histamine-releasing factors (HRF) that are associated with the allergic reactions to parasites. Herein, we described the cloning, heterologous expression, purification and functional characterization of a novel member of the TCTP family from the Loxosceles intermedia venom gland. This recombinant protein, named LiRecTCTP, causes edema, enhances vascular permeability and is likely related to the inflammatory activity of the venom. Moreover, LiRecTCTP presents an immunological relationship with mammalian TCTPs. PMID- 22051633 TI - More in Montreal. PMID- 22051634 TI - The mind's tangled web. PMID- 22051632 TI - Enhancement of the behavioral effects of endogenous and exogenous cannabinoid agonists by phenylmethyl sulfonyl fluoride. AB - Marijuana's effects in humans are most often reported as intoxicating or therapeutic; yet, some humans report dysphoria or other negative affect. To evaluate whether differences in endocannabinoid levels might account for this variability, the present study examined whether sensitivity to cannabinoids changed when anandamide (AEA) metabolism was inhibited through administration of phenylmethyl sulfonyl fluoride (PMSF) a non-specific irreversible amidase inhibitor. Male Long Evans rats were trained to discriminate 3 mg/kg Delta(9) tetrahydrocannabinol (THC) versus vehicle in 2-lever drug discrimination procedure. ED(50)s for THC and CP 55,940 were lower when administered with PMSF than alone. PMSF administration also potentiated characteristic cannabimimetic effects of THC in ICR mice. Potentiation of AEA's in vivo effects by PMSF were also observed, primarily as a consequence of PMSF inhibition of the enzyme fatty acid amide hydrolase. Enhancement of the effects of THC and CP 55,940 through this mechanism is unlikely, as these cannabinoids are predominantly metabolized through the P450 system. Mass spectrometry revealed that, in the presence of THC, endogenous AEA levels in the brain decreased and that this decrease was prevented by PMSF, suggesting that increased AEA levels may have acted additively with exogenously administered cannabinoids to increase cannabimimetic effects. These findings may account for the varying affect in response to marijuana in humans or cannabinoids in animals while also suggesting that metabolic inhibitors of AEA may potentiate marijuana's intoxicating effects in humans. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22051635 TI - Collision course. PMID- 22051636 TI - Scientists and the media must give a balanced view. PMID- 22051648 TI - Mississippi to vote on 'personhood'. PMID- 22051649 TI - Mental-health guide accused of overreach. PMID- 22051650 TI - Report finds massive fraud at Dutch universities. PMID- 22051651 TI - Drilling ship to probe Japanese quake zone. PMID- 22051653 TI - Megatelescopes look for support. PMID- 22051652 TI - Research cuts hit the DNA business. PMID- 22051655 TI - Special issue on neuroscience: The autism enigma. PMID- 22051656 TI - The prevalence puzzle: Autism counts. PMID- 22051657 TI - Scientists and autism: When geeks meet. PMID- 22051658 TI - Autism's fight for facts: A voice for science. PMID- 22051659 TI - Changing perceptions: The power of autism. PMID- 22051660 TI - Science and law: Improve statistics in court. PMID- 22051663 TI - Patenting: European stem-cell ruling is misleading. PMID- 22051665 TI - Economic crisis: Call to support Greek research reforms. PMID- 22051664 TI - Epidemic: Control of dengue fever in Pakistan. PMID- 22051666 TI - Walking statues: Easter Island's complex history. PMID- 22051667 TI - Steve Jobs (1955-2011). PMID- 22051668 TI - Societal collapse: Drought and the Maya. PMID- 22051669 TI - Neuroscience: Periodicity without rhythmicity. PMID- 22051670 TI - Quantum computing: Diamond and silicon converge. PMID- 22051671 TI - Immunology: A heavyweight knocked out. PMID- 22051672 TI - Climate change: Man-made cyclones. PMID- 22051673 TI - Palaeontology: Fresh light on southern early mammals. PMID- 22051674 TI - Subsurface water and clay mineral formation during the early history of Mars. AB - Clay minerals, recently discovered to be widespread in Mars's Noachian terrains, indicate long-duration interaction between water and rock over 3.7 billion years ago. Analysis of how they formed should indicate what environmental conditions prevailed on early Mars. If clays formed near the surface by weathering, as is common on Earth, their presence would indicate past surface conditions warmer and wetter than at present. However, available data instead indicate substantial Martian clay formation by hydrothermal groundwater circulation and a Noachian rock record dominated by evidence of subsurface waters. Cold, arid conditions with only transient surface water may have characterized Mars's surface for over 4 billion years, since the early-Noachian period, and the longest-duration aqueous, potentially habitable environments may have been in the subsurface. PMID- 22051676 TI - Room temperature coherent control of defect spin qubits in silicon carbide. AB - Electronic spins in semiconductors have been used extensively to explore the limits of external control over quantum mechanical phenomena. A long-standing goal of this research has been to identify or develop robust quantum systems that can be easily manipulated, for future use in advanced information and communication technologies. Recently, a point defect in diamond known as the nitrogen-vacancy centre has attracted a great deal of interest because it possesses an atomic-scale electronic spin state that can be used as an individually addressable, solid-state quantum bit (qubit), even at room temperature. These exceptional quantum properties have motivated efforts to identify similar defects in other semiconductors, as they may offer an expanded range of functionality not available to the diamond nitrogen-vacancy centre. Notably, several defects in silicon carbide (SiC) have been suggested as good candidates for exploration, owing to a combination of computational predictions and magnetic resonance data. Here we demonstrate that several defect spin states in the 4H polytype of SiC (4H-SiC) can be optically addressed and coherently controlled in the time domain at temperatures ranging from 20 to 300 kelvin. Using optical and microwave techniques similar to those used with diamond nitrogen-vacancy qubits, we study the spin-1 ground state of each of four inequivalent forms of the neutral carbon-silicon divacancy, as well as a pair of defect spin states of unidentified origin. These defects are optically active near telecommunication wavelengths, and are found in a host material for which there already exist industrial-scale crystal growth and advanced microfabrication techniques. In addition, they possess desirable spin coherence properties that are comparable to those of the diamond nitrogen-vacancy centre. This makes them promising candidates for various photonic, spintronic and quantum information applications that merge quantum degrees of freedom with classical electronic and optical technologies. PMID- 22051675 TI - Melanopsin signalling in mammalian iris and retina. AB - Non-mammalian vertebrates have an intrinsically photosensitive iris and thus a local pupillary light reflex (PLR). In contrast, it is thought that the PLR in mammals generally requires neuronal circuitry connecting the eye and the brain. Here we report that an intrinsic component of the PLR is in fact widespread in nocturnal and crepuscular mammals. In mouse, this intrinsic PLR requires the visual pigment melanopsin; it also requires PLCbeta4, a vertebrate homologue of the Drosophila NorpA phospholipase C which mediates rhabdomeric phototransduction. The Plcb4(-/-) genotype, in addition to removing the intrinsic PLR, also essentially eliminates the intrinsic light response of the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (M1 ipRGCs), which are by far the most photosensitive ipRGC subtype and also have the largest response to light. Ablating in mouse the expression of both TRPC6 and TRPC7, members of the TRP channel superfamily, also essentially eliminated the M1 ipRGC light response but the intrinsic PLR was not affected. Thus, melanopsin signalling exists in both iris and retina, involving a PLCbeta4-mediated pathway that nonetheless diverges in the two locations. PMID- 22051677 TI - Synthesis of macrocyclic natural products by catalyst-controlled stereoselective ring-closing metathesis. AB - Many natural products contain a C = C double bond through which various other derivatives can be prepared; the stereochemical identity of the alkene can be critical to the biological activities of such molecules. Catalytic ring-closing metathesis (RCM) is a widely used method for the synthesis of large unsaturated rings; however, cyclizations often proceed without control of alkene stereochemistry. This shortcoming is particularly costly when the cyclization reaction is performed after a long sequence of other chemical transformations. Here we outline a reliable, practical and general approach for the efficient and highly stereoselective synthesis of macrocyclic alkenes by catalytic RCM; transformations deliver up to 97% of the Z isomer owing to control induced by a tungsten-based alkylidene. Utility is demonstrated through the stereoselective preparation of epothilone C (refs 3-5) and nakadomarin A (ref. 6), the previously reported syntheses of which have been marred by late-stage, non-selective RCM. The tungsten alkylidene can be manipulated in air, delivering the products in useful yields with high stereoselectivity. As a result of efficient RCM and re incorporation of side products into the catalytic cycle with minimal alkene isomerization, desired cyclizations proceed in preference to alternative pathways, even under relatively high substrate concentration. PMID- 22051678 TI - Arabian Sea tropical cyclones intensified by emissions of black carbon and other aerosols. AB - Throughout the year, average sea surface temperatures in the Arabian Sea are warm enough to support the development of tropical cyclones, but the atmospheric monsoon circulation and associated strong vertical wind shear limits cyclone development and intensification, only permitting a pre-monsoon and post-monsoon period for cyclogenesis. Thus a recent increase in the intensity of tropical cyclones over the northern Indian Ocean is thought to be related to the weakening of the climatological vertical wind shear. At the same time, anthropogenic emissions of aerosols have increased sixfold since the 1930s, leading to a weakening of the southwesterly lower-level and easterly upper-level winds that define the monsoonal circulation over the Arabian Sea. In principle, this aerosol driven circulation modification could affect tropical cyclone intensity over the Arabian Sea, but so far no such linkage has been shown. Here we report an increase in the intensity of pre-monsoon Arabian Sea tropical cyclones during the period 1979-2010, and show that this change in storm strength is a consequence of a simultaneous upward trend in anthropogenic black carbon and sulphate emissions. We use a combination of observational, reanalysis and model data to demonstrate that the anomalous circulation, which is radiatively forced by these anthropogenic aerosols, reduces the basin-wide vertical wind shear, creating an environment more favourable for tropical cyclone intensification. Because most Arabian Sea tropical cyclones make landfall, our results suggest an additional impact on human health from regional air pollution. PMID- 22051679 TI - Highly specialized mammalian skulls from the Late Cretaceous of South America. AB - Dryolestoids are an extinct mammalian group belonging to the lineage leading to modern marsupials and placentals. Dryolestoids are known by teeth and jaws from the Jurassic period of North America and Europe, but they thrived in South America up to the end of the Mesozoic era and survived to the beginnings of the Cenozoic. Isolated teeth and jaws from the latest Cretaceous of South America provide mounting evidence that, at least in western Gondwana, dryolestoids developed into strongly endemic groups by the Late Cretaceous. However, the lack of pre-Late Cretaceous dryolestoid remains made study of their origin and early diversification intractable. Here we describe the first mammalian remains from the early Late Cretaceous of South America, including two partial skulls and jaws of a derived dryolestoid showing dental and cranial features unknown among any other group of Mesozoic mammals, such as single-rooted molars preceded by double rooted premolars, combined with a very long muzzle, exceedingly long canines and evidence of highly specialized masticatory musculature. On one hand, the new mammal shares derived features of dryolestoids with forms from the Jurassic of Laurasia, whereas on the other hand, it is very specialized and highlights the endemic, diverse dryolestoid fauna from the Cretaceous of South America. Our specimens include only the second mammalian skull known for the Cretaceous of Gondwana, bridging a previous 60-million-year gap in the fossil record, and document the whole cranial morphology of a dryolestoid, revealing an unsuspected morphological and ecological diversity for non-tribosphenic mammals. PMID- 22051680 TI - Grid cells without theta oscillations in the entorhinal cortex of bats. AB - Grid cells provide a neural representation of space, by discharging when an animal traverses through the vertices of a periodic hexagonal grid spanning the environment. Although grid cells have been characterized in detail in rats, the fundamental question of what neural dynamics give rise to the grid structure remains unresolved. Two competing classes of models were proposed: network models, based on attractor dynamics, and oscillatory interference models, which propose that interference between somatic and dendritic theta-band oscillations (4-10 Hz) in single neurons transforms a temporal oscillation into a spatially periodic grid. So far, these models could not be dissociated experimentally, because rodent grid cells always co-exist with continuous theta oscillations. Here we used a novel animal model, the Egyptian fruit bat, to refute the proposed causal link between grids and theta oscillations. On the basis of our previous finding from bat hippocampus, of spatially tuned place cells in the absence of continuous theta oscillations, we hypothesized that grid cells in bat medial entorhinal cortex might also exist without theta oscillations. Indeed, we found grid cells in bat medial entorhinal cortex that shared remarkable similarities to rodent grid cells. Notably, the grids existed in the absence of continuous theta band oscillations, and with almost no theta modulation of grid-cell spiking--both of which are essential prerequisites of the oscillatory interference models. Our results provide a direct demonstration of grid cells in a non-rodent species. Furthermore, they strongly argue against a major class of computational models of grid cells. PMID- 22051682 TI - Ethnic differences in self-rated overweight and association with reporting weight loss action: the SUNSET study. AB - AIM: To investigate ethnic differences in self-rated overweight and self-reported weight loss action. METHODS: Cross-sectional study (conducted in 2001-03) of 1441 residents (35-60 years) of Amsterdam, The Netherlands: Surinamese of South Asian (SA-Sur) and African (Afr-Sur) origin and ethnic Dutch. Self-rated overweight and self-reported weight loss action assessed by questionnaire. Height, weight and waist circumference (WC) measured in a clinic setting. RESULTS: Compared with ethnic Dutch and adjusting for BMI, Afr-Sur men [odds ratio (OR) 0.32; 95% CI 0.19-0.57] and women (OR 0.54; 95% CI 0.34-0.86) were less likely to rate themselves as overweight. However, adjustment for WC reduced differences in self rated overweight (men: OR 0.79; 95% CI 0.46-1.35; women: OR 0.89; 95% CI 0.59 1.36). SA-Sur participants did not differ significantly from ethnic Dutch when adjusting for either BMI or WC. Surinamese participants were significantly more likely to report weight loss action independent of BMI, WC or self-rated overweight. In Afr-Sur men, elevated WC, not BMI was associated with reported weight loss action (OR 2.31; 95% CI 1.35-3.99 vs. OR 1.52, 95% CI 0.89-2.58, respectively). CONCLUSION: In this population, differences in self-rated overweight were explained by measured weight variables (BMI or WC). Our results do not support the hypothesis that Surinamese migrants would be less likely to be attempting weight loss than their Dutch peers. Further research into the reasons underlying this finding and associated weight loss behaviour seems indicated. PMID- 22051683 TI - Parents' alcohol use: gender differences in the impact of household and family chores. AB - BACKGROUND: Social roles influence alcohol use. Nevertheless, little is known about how specific aspects of a given role, here parenthood, may influence alcohol use. The research questions for this study were the following: (i) are family-related indicators (FRI) linked to the alcohol use of mothers and fathers? and (ii) does the level of employment, i.e. full-time, part-time employment or unemployment, moderate the relationship between FRI and parental alcohol use? METHODS: Survey data of 3217 parents aged 25-50 living in Switzerland. Mean comparisons and multiple regression models of annual frequency of drinking and risky single occasion drinking, quantity per day on FRI (age of the youngest child, number of children in the household, majority of child-care/household duties). RESULTS: Protective relationships between FRI and alcohol use were observed among mothers. In contrast, among fathers, detrimental associations between FRI and alcohol use were observed. Whereas maternal responsibilities in general had a protective effect on alcohol use, the number of children had a detrimental impact on the quantity of alcohol consumed per day when mothers were in paid employment. Among fathers, the correlations between age of the youngest child, number of children and frequency of drinking was moderated by the level of paid employment. CONCLUSION: The study showed that in Switzerland, a systematic negative relationship was more often found between FRI and women's drinking than men's. Evidence was found that maternal responsibilities per se may protect from alcohol use but can turn into a detrimental triangle if mothers are additionally in paid employment. PMID- 22051684 TI - CR@BaSO4: an acid rain-indicating material. AB - The CR@BaSO(4) hybrid was synthesized, characterized and used as an acid rain indicating (ARI) material. A painted ARI umbrella was discolored after exposure to simulated acid rain of pH 5 or less and returned to the initial color after the rain stopped. Such a functionalized material may make acid rain visual to remind people in real-time. PMID- 22051685 TI - Synthesis, characterization and magnetic properties of hollow microspheres with micro-mesoporous shells assembled from cobalt-based ferrocenyl coordination polymers. AB - Hollow magnetic microspheres with micro-mesoporous shells were constructed with layered cobalt-based ferrocenyl coordination polymers (Co-Fc-HCPS) through a one step Ostwald ripening process. The diameters of microspheres and corresponding cavities were controlled in the range of several microns by tuning the reaction time and reactant concentration, which would attribute the microspheres with high loading, and enhanced mass diffusion and transfer efficiency. The high crystallinity of hollow microspheres allowed determination of the crystal structure of cobalt-based ferrocenyl coordination polymer, which crystallized in Brucite-type layered structure with the formula of Co(4)(OH)(4)(FcDC)(2), (H(2)FcDC=1,1'-ferrocenedicarboxylic acid), by combination of powder X-ray diffraction (PXRD), energy-dispersive X-ray spectroscopy (EDX), element analysis (EA), and Fourier transform infrared spectroscopy (FT-IR). N(2) adsorption/desorption investigation revealed the existence of both mesopores around 3.81 nm and micropores of ca. 1 nm in the shells. The hollow microspheres exhibited spin-canted antiferromagnetism with weak ferromagnetic ordering below ~52 K, which showed a remanent magnetization (Mr) of 1.0 MU(B) and a large coercive field (Hc) of 5 kOe at 7 K. PMID- 22051686 TI - Deposition of gold nanoparticles on beta-FeOOH nanorods for detecting melamine in aqueous solution. AB - This study demonstrates a facile but efficient approach to deposit metallic (gold) nanoparticles on beta-FeOOH nanorods to obtain Au/beta-FeOOH nanocomposites without the assistance of any polymers or surfactants at ambient conditions. In this method, a strong reducing agent (NaBH(4)) can be used to extensively produce Au nanoparticles, converting beta-FeOOH into Fe(3)O(4) and depositing gold particles onto magnetic Fe(3)O(4) simultaneously. The microstructure, composition, and chemical properties of the obtained nanocomposites are characterized by various advanced techniques, including transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV-vis spectroscopy. Moreover, the Au/beta-FeOOH nanocomposite can be used to detect trace melamine using UV spectrum in the ultraviolet wavelength range (190-260 nm), in which the nanocomposites show a higher sensitivity toward melamine due to the promotion of symmetry-forbidden bands (n->pi(*)) of melamine molecules and also avoid the disturbance of commercial products containing solid colloids or food colorings that distort visual spectrum during the detection of chemical sensing. The deposition mechanisms and their sensing detection toward melamine are discussed. PMID- 22051687 TI - Self-assembled amorphous drug-polyelectrolyte nanoparticle complex with enhanced dissolution rate and saturation solubility. AB - The dissolution rate and solubility of poorly soluble drugs can be enhanced by formulating them into stable amorphous nanoparticle complex (nanoplex). For this purpose, a highly sustainable self-assembly drug-polyelectrolyte complexation process is developed, with ciprofloxacin and dextran sulfate as the drug and polyelectrolyte models, respectively. The nanoplex are prepared by mixing two aqueous salt solutions - one containing the drug and the other containing the oppositely charged polyelectrolyte. The nanoplex suspension is transformed into stable dry-powder form by freeze-drying. The effects of drug concentration, drug to-polyelectrolyte charge ratio, and salt concentration on the complexation efficiency, yield, drug loading, and nanoplex morphology are examined. The dissolution rates and solubility of the nanoplex are characterized and compared to raw drug crystals. Nearly spherical amorphous nanoplex having fairly uniform sizes in the range of 200-400 nm and 80% drug loading are successfully produced at >=80% complexation efficiency and yield. The complexation efficiency is governed by the drug concentration and its ratio to the salt concentration. The nanoplex powders exhibit approximately twice higher dissolution rate and solubility than raw drug crystals and remain stable after one-month storage. Overall, amorphous nanoplex represent a promising bioavailability-enhanced formulation of poorly soluble drugs owed to their superior characteristics and ease of preparation. PMID- 22051688 TI - Validity of a brief self-report instrument for assessing compliance with physical activity guidelines amongst adolescents. AB - OBJECTIVES: To examine the validity of a brief self-report questionnaire for assessing physical activity, and compliance and non-compliance with moderate-to vigorous physical activity (MVPA) recommendations in Australian adolescents against accelerometry. DESIGN: Cross-sectional study. METHODS: MVPA of 203 adolescents (124 females, 79 males) aged 15-17 years was objectively assessed for 8 consecutive days using uni-axial accelerometers and calculated using age specific cut-points. Adolescents self-reported the number of days (0-7) they were physically active for a total of at least 60 min/day (1) over the past 7 days and (2) over a typical week. Compliance with physical activity recommendations was defined as (1) 5 and (2) 7 days of self-reported MVPA (of at least 60 min/day), and (3) >=60 min MVPA per average day, and (4) >60 min MVPA on every day according to accelerometry. Spearman's Rho correlations analysed the association between accelerometry-derived MVPA/day and self-reported MVPA days/week for the whole sample, sex and weight status. Percent agreement determined the proportion of adolescents correctly identified as not meeting physical activity recommendations (specificity) or as meeting physical activity recommendations (sensitivity) according to the self-report questionnaire. RESULTS: Moderate to large correlations were found between the self-report and accelerometer data (0.2 0.51) across population subgroups. The percent agreement between the self-report and accelerometry data was good for specificity; however, the sensitivity was low, potentially due to poor compliance with recommendations. CONCLUSIONS: Compared to accelerometry, the brief MVPA self-report questionnaire appears to have acceptable validity for measuring non-compliance with physical activity recommendations in 15-17 year old adolescents. PMID- 22051689 TI - Regarding cancer predisposition detected by CHG arrays. PMID- 22051692 TI - Optical super-resolution microscopy in neurobiology. AB - Understanding the highly plastic nature of neurons requires the dynamic visualization of their molecular and cellular organization in a native context. However, due to the limited resolution of standard light microscopy, many of the structural specializations of neurons cannot be resolved. A recent revolution in light microscopy has given rise to several super-resolution light microscopy methods yielding 2-10-fold higher resolution than conventional microscopy. We here describe the principles behind these techniques as well as their application to the analysis of the molecular architecture of the synapse. Furthermore, we discuss the potential for continued development of super-resolution microscopy as necessary for live imaging of neuronal structure and function in the brain. PMID- 22051693 TI - Depolarization gates spine calcium transients and spike-timing-dependent potentiation. AB - Timing-dependent long-term potentiation (t-LTP) is induced when synaptic activity is immediately followed by one or more back-propagating action potentials (bAPs) in the postsynaptic cell. As a mechanistic explanation, it has been proposed that the bAP removes the Mg2+ block of synaptic NMDA receptors, allowing for rapid Ca2+ entry at the active synapse. Recent experimental studies suggest that this model is incomplete: NMDA receptor-based coincidence detection requires strong postsynaptic depolarization, usually provided by AMPA receptor currents. Apparently, the brief AMPA-EPSP does not only enable t-LTP, it is also responsible for the very narrow time window for t-LTP induction. The emerging consensus puts the spine in the center of coincidence detection, as active conductances on the spine together with the electrical resistance of the spine neck regulate the depolarization of the spine head and thus Ca2+ influx during pairing. A focus on postsynaptic voltage during synaptic activation not only encompasses spike-timing-dependent plasticity (STDP), but explains also the cooperativity and frequency-dependence of plasticity. PMID- 22051694 TI - Regulation of AMPA receptor surface diffusion by PSD-95 slots. AB - Excitatory synaptic transmission is largely mediated by AMPA receptors (AMPARs) present at the postsynaptic density. Recent studies in single molecule tracking of AMPAR has revealed that extrasynaptic AMPARs are highly mobile and thus might serve as a readily available pool for their synaptic recruitment during synaptic plasticity events such as long-term potentiation (LTP). Because this hypothesis relies on the cell's ability to increase the number of diffusional traps or 'slots' at synapses during LTP, we will review a number of protein-protein interactions that might impact AMPARs lateral diffusion and thus potentially serve as slots. Recent studies have identified the interaction between the AMPAR Stargazin complex and PSD-95 as the minimal components of the diffusional trapping slot. We will overview the molecular basis of this critical interaction, its activity-dependent regulation and its potential contribution to LTP. PMID- 22051695 TI - Patterning cells and shear flow conditions: convenient observation of endothelial cell remoulding, enhanced production of angiogenesis factors and drug response. AB - We present a method that allows patterning cells and shear flow conditions for endothelial cell based assays. This method is novel in combining (1) cell culture on the surface of a substrate both topographically and chemically patterned; (2) multi-shear flow assays after covering the cell substrate with a microfluidic cover plate containing microchannels of different channel widths, and (3) conventional immunostaining assays after removal of the cover plate. This method has the advantage of performing cell cultures and immunoassays in standard cell biology environments with open access, facilitating the formation of confluent cell layers and the observation of cell responses to shear-flow and drug stimulations. To obtain multi-shear stress conditions, a single channel with stepwise increasing channel widths was patterned on the surfaces of both the substrate and the microfluidic cover plate. As results, we observed excellent viability of endothelial cells in the whole range of applied shear stresses (0-25 dyn cm(-2)) and shear stress dependent cytoskeleton remoulding, activation of von Willebrand factor (vWF), and re-organisation of angiogenesis factors such as tetra peptide acetyl-Ser-Asp-Lys-Pro (AcSDKP) of endothelial cells. To validate this approach for drug analysis, we also studied drug effects under shear stress conditions. Our results indicate that the drug effect of combretastatin A-4, an anti-tumour vascular targeting drug, could be significantly enhanced under shear flow conditions. PMID- 22051696 TI - Induction and maintenance of allergen-specific FOXP3+ Treg cells in human tonsils as potential first-line organs of oral tolerance. AB - BACKGROUND: Tonsils are strategically located in the gateway of both alimentary and respiratory tracts representing the first contact point of food and aeroallergens with the immune system. Tonsillectomy removes only the palatine tonsils and sometimes adenoids. Lingual tonsil is anatomically big and remains lifelong intact. OBJECTIVE: The aim of this study was to demonstrate cellular and molecular mechanisms of oral tolerance induction to food and aeroallergens in human tonsils. METHODS: Tonsil allergen-specific FOXP3(+) regulatory T (Treg) cells, plasmacytoid dendritic cells (pDCs), and myeloid dendritic cells were characterized by flow cytometry and suppressive assays. Intracellular staining, [(3)H]-thymidine incorporation, and carboxy-fluorescein succinimidyl ester dilution experiments were performed. Tonsil biopsies were analyzed by confocal microscopy. RESULTS: CD4(+)FOXP3(+) Treg cells and pDCs constitute important T- and dendritic cell-compartments in palatine and lingual tonsils. Tonsil pDCs have the ability to generate functional CD4(+)CD25(+)CD127(-)FOXP3(+) Treg cells with suppressive property from naive T cells. CD4(+)FOXP3(+) Treg cells proliferate and colocalize with pDCs in vivo in T-cell areas of lingual and palatine tonsils. Tonsil T cells did not proliferate to common food and aeroallergens. Depletion of FOXP3(+) Treg cells enables the allergen-induced proliferation of tonsil T cells, indicating an active role of Treg cells in allergen-specific T-cell unresponsiveness. High numbers of major birch pollen allergen, Bet v 1-specific CD4(+)FOXP3(+) Treg cells, are identified in human tonsils compared with peripheral blood. A positive correlation between the percentages of FOXP3(+) Treg cells and pDCs is observed in tonsils from nonatopic individuals. CONCLUSION: Functional allergen-specific Treg cells are identified both in lingual and in palatine tonsils. PMID- 22051697 TI - Genome-wide association study reveals class I MHC-restricted T cell-associated molecule gene (CRTAM) variants interact with vitamin D levels to affect asthma exacerbations. AB - BACKGROUND: It has recently been shown that vitamin D deficiency can increase asthma development and severity and that variations in vitamin D receptor genes are associated with asthma susceptibility. OBJECTIVE: We sought to find genetic factors that might interact with vitamin D levels to affect the risk of asthma exacerbation. METHODS: We conducted a genome-wide study of gene-vitamin D interaction on asthma exacerbations using population-based and family-based approaches on 403 subjects and trios from the Childhood Asthma Management Program. Twenty-three polymorphisms with significant interactions were studied in a replication analysis in 584 children from a Costa Rican cohort. RESULTS: We identified 3 common variants in the class I MHC-restricted T cell-associated molecule gene (CRTAM) that were associated with an increased rate of asthma exacerbations based on the presence of a low circulating vitamin D level. These results were replicated in a second independent population (unadjusted combined interaction, P = .00028-.00097; combined odds ratio, 3.28-5.38). One variant, rs2272094, is a nonsynonymous coding polymorphism of CRTAM. Functional studies on cell lines confirmed the interaction of vitamin D and rs2272094 on CRTAM expression. CRTAM is highly expressed in activated human CD8(+) and natural killer T cells, both of which have been implicated in asthmatic patients. CONCLUSION: The findings highlight an important gene-environment interaction that elucidates the role of vitamin D and CD8(+) and natural killer T cells in asthma exacerbation in a genome-wide gene-environment interaction study that has been replicated in an independent population. The results suggest the potential importance of maintaining adequate vitamin D levels in subsets of high-risk asthmatic patients. PMID- 22051698 TI - Evaluation of national institute of allergy and infectious diseases/food allergy and anaphylaxis network criteria for the diagnosis of anaphylaxis in emergency department patients. AB - BACKGROUND: Diagnostic criteria were proposed at the Second Symposium on the Definition and Management of Anaphylaxis convened by the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN). Validation is needed before these criteria can be widely adapted into clinical practice. OBJECTIVE: Our aim was to retrospectively assess the diagnostic accuracy of the NIAID/FAAN criteria for the diagnosis of anaphylaxis in emergency department (ED) patients. METHODS: A retrospective cohort study of ED patients presenting from April to October 2008 was conducted. Patients given a diagnosis of an allergic reaction or anaphylaxis and a subset of patients with related diagnoses were included. Electronic medical records were reviewed and data were abstracted to determine whether the NIAID/FAAN criteria were met. Records were also independently reviewed in a blinded fashion by 2 experienced attending allergists. Final diagnosis by allergists was considered the reference standard. RESULTS: Of 214 patients, 86 (40.2%) met the NIAID/FAAN criteria for anaphylaxis. Allergists gave 61 (28.5%) patients diagnoses of anaphylaxis, 59 (96.7%) of whom satisfied the NIAID/FAAN criteria. The interrater agreement between allergists was substantial (kappa = 0.77). The test characteristics of the NIAID/FAAN criteria were as follows: sensitivity, 96.7% (95% CI, 88.8% to 99.1%); specificity, 82.4% (95% CI, 75.5% to 87.6%); positive predictive value, 68.6% (95% CI, 58.2% to 77.4%); negative predictive value, 98.4% (95% CI, 94.5% to 99.6%); positive likelihood ratio, 5.48; and negative likelihood ratio, 0.04. CONCLUSIONS: These results suggest that the NIAID/FAAN criteria are highly sensitive but less specific and are likely to be useful in the ED for the diagnosis of anaphylaxis. PMID- 22051699 TI - Gold-peptide nanoconjugate cellular uptake is modulated by serum proteins. AB - Gold nanoparticles (Au NPs, 20 nm) were conjugated with two different cysteine terminated peptides. Radio-ligand binding studies were conducted to characterize Au NP-peptide binding, suggesting both covalent and noncovalent interactions. The interactions of serum proteins with Au NP-peptide nanoconjugates were determined using gel electrophoresis and dynamic light scattering. Serum proteins rapidly bound the nanoconjugates (15 minutes). The cellular uptake of free peptides and nanoconjugates into mouse myogenic (Sol8) cells was investigated in the absence or presence of serum. In the absence of serum, peptides presented as nanoconjugates showed significantly higher intracellular fluorescence signals compared to those in the presence of serum (P < 0.05), suggesting that serum proteins inhibit Au NP-mediated peptide delivery. The cellular uptake of nanoconjugates was also confirmed using transmission electron microscopy. These data suggest that Au NP-peptide nanoconjugates are a useful platform for intracellular delivery of therapeutics. However, a deeper understanding of the mechanisms regulating their uptake and intracellular trafficking is needed. PMID- 22051700 TI - Nonylphenol polyethoxylates induce phosphorylation of histone H2AX. AB - Nonylphenol polyethoxylates (NPEOs) are non-ionic surfactants widely used for industrial and household purposes. Since biodegraded short chain NPEOs were reported to elicit estrogenic activity in organisms, numerous studies have been carried out to assess the endocrine-disrupting potential of NPEOs; however, the genotoxicity of the compounds is not fully known, let alone the relationship between the genotoxic potential and number of ethylene oxide (EO) units of NPEOs. In this study, we examined the genotoxicity of NPEO(n) having various EO units (n=0, 5, 10, 15, 20, 30, 40 and 70) in a human breast adenocarcinoma cell line, MCF-7, based on the phosphorylation of histone H2AX (gamma-H2AX), recently regarded as a sensitive marker for DNA damage. We clarified that NPEOs have the ability to form gamma-H2AX via activation of ATM or DNA-PK, a general signaling pathway in response to DSBs, and this ability was strongly dependent on the number of EO units, that is, NPEO(0-15) having smaller numbers of EO units more readily generated gamma-H2AX. Flow cytometric analysis revealed that the generation of gamma-H2AX was independent of cell cycle phases. Although the mechanism by which the NPEOs generated gamma-H2AX was not able to be elucidated in the present study, it was clear that the involvement of reactive oxygen species and apoptotic DNA fragmentation were not causal factors. The generation of gamma-H2AX means the formation of DSBs, the worst type of DNA damage. The results indicated that attention should be paid to degradated short chain NPEOs and their genotoxicity. PMID- 22051702 TI - Diruthenium(II,III) tetramidates as a new class of oxygenation catalysts. AB - Two new diruthenium(II,III) tetramidate compounds, Ru(2)(NHOCC(CH(3))(2))(4)Cl (1) and Ru(2)(NHOCCH(2)CH(3))(4)Cl (2) have been prepared and structurally characterized by X-ray crystallography. The activity of promoting sulfide oxygenation using simple oxidants such as hydrogen peroxide (H(2)O(2)) and tert butyl hydroperoxide (TBHP) was studied. A UV-kinetics study indicated that the initial rates of 1 and 2 are comparable to the previously studied diruthenium tetracarboxylates in promoting TBHP oxygenation of methyl phenyl sulfide (MPS). Using excess oxidant and CH(3)CN as the solvent, organic sulfides MPS and diphenyl sulfide (PPS) were oxidized using 1 mol% of the catalytic species. Compound 1 is more effective than 2 in converting sulfides to sulfoxide under the same conditions. Fast conversion was achieved when the reactions were carried out in the solvent-free conditions, and the major oxidation product was the sulfoxide. The electronic structure of the title compounds was studied with DFT calculations to gain an understanding of the activation of peroxy reagents. PMID- 22051701 TI - Anti-diabetic potential of ursolic acid stearoyl glucoside: a new triterpenic gycosidic ester from Lantana camara. AB - A new stearoyl glucoside of ursolic acid, urs-12-en-3beta-ol-28-oic acid 3beta-D glucopyranosyl-4'-octadecanoate and other compounds were isolated from the leaves of Lantana camara L. The structure of this new glycoside was elucidated and established by standard spectroscopic methods. In streptozotocin-induced diabetic rats it showed significant reduction in blood glucose level. PMID- 22051703 TI - The built environment and physical activity. AB - Regular physical activity has many health benefits, but in spite of the benefits many Americans are not sufficiently active. There is increasing recognition of the importance of environmental factors-including the built environment-to help promote physical activity. The built environment describes physical or manmade features such as sidewalks, streetlights, traffic and parks that may promote or discourage activity. This synthesis examines the evidence on the built environment-proximity to destinations, sidewalks, aesthetics, access to parks and open spaces, and the walkability of the community-and the relationship to increased physical activity. Findings include: There is reasonably strong evidence of an association between many factors of the built environment and increased physical activity, but the evidence on whether or not the built environment promotes activity is weak. Most research shows that individual and societal factors are stronger drivers of activity than the built environment. PMID- 22051705 TI - [Availability of physicians and specialists in Chile]. AB - The availability and planning of Human Resources are important issues in many countries, as it is a key factor to cope with the critical challenges of Health Care Systems. In Chile, the Ministry of Health has undertaken several studies in order to improve knowledge about the medical workforce both in public and private sectors. The aim of this paper is to update and systematize the existing data on physicians and specialists availability in Chile. Several information sources were crossed to obtain new and more precise figures about this topic. According to the Internal Revenue System, 29.996 physicians practice medicine in the country, 43% of them hired in public services, part or full time. There is a high concentration of professionals in the central regions of Chile. Being the overall density of physicians of one per 559 inhabitants, the figures in the central region is one per 471 and one per more than 800 in the South and North. Between 2004 and 2008, the public sector increased its physician workforce by more than 80% in primary health care and more than 20% in the secondary and tertiary levels. This paper presents a method for a more rigorous identification of the categories of general practitioner and specialist respectively, and the results obtained from the databases used. PMID- 22051704 TI - The associations of parental under-education and unemployment on the risk of preterm birth: 2003 Korean National Birth Registration database. AB - OBJECTIVES: This study aimed to investigate the associations of combined parental low educational level and combined parental unemployment on the risk of preterm birth (PTB) in Korea. METHODS: Data on 427,857 singleton births were obtained from the National Birth Registration (NBR) database in 2003 and analyzed. Parental education and parental employment status were combined as exposure for analysis. Place of birth, sex, marital status, parental age and parity were included for analysis of unconditional multiple logistic regressions. PTB was defined as birth before a gestational age of 37 complete weeks. RESULTS: Group of the lowest educational level, below high school, had the highest odds of PTB in both father and mother in multivariable analysis [odds ratio (OR) 1.15 and 1.16, respectively]. After combining parental educational status for the multivariable analysis, the highest probability of PTB was in families where both parents had below college level education (OR 1.22). As for paternal employment, the multivariable analysis showed an increased rate of PTB occurred where the father was unemployed (OR 1.11). After combining the employment status of both parents, the multivariable analysis revealed that PTB was only significant in families where both parents were unemployed (OR 1.09). CONCLUSIONS: We found that combined parental low educational level and combined parental unemployment increased the likelihood of preterm birth. PMID- 22051706 TI - [Anxiety, depression and self-concept among morbid obese patients before and after bariatric surgery]. AB - BACKGROUND: There is conflicting evidence about the emotional impact of bariatric surgery among obese individuals. AIM: To evaluate anxiety, depression and self concept, before and after bariatric surgery among patients with morbid obesity. MATERIAL AND METHODS: Fifteen males and 5 females aged 28 to 61 years with a mean body mass index of 42.6 +/- 5 kg/m(2), were studied. Grid Technique (TR), Personal Self Evaluation Questionnaire (OQ-45.2) and Anxiety Sate-Trait Inventory (STAI) were applied before and six months after bariatric surgery. RESULTS: After surgery, the scores of self-esteem, well-being, flexibility, attraction, self acceptance, confidence and guilt improved significantly. STAI and OQ-45.2 anxiety and depressive symptoms assessment were in the normal range before and after surgery. However, after surgery, there was a significant decrease in these sub scales in the OQ-45.2. No significant changes in anxiety measured using the STAI, were observed after surgery. CONCLUSIONS: Six months after bariatric surgery, positive changes were found in self-concept, and overall well-being. PMID- 22051707 TI - [Validation of the WHOQOL-BREF quality of life questionnaire among Chilean older people]. AB - BACKGROUND: The WHOQOL-BREF is a generic questionnaire to measure quality of life created by the Study Group on Quality of Life of the World Health Organization. AIM: To adapt and evaluate the psychometric properties of the Spanish version of the WHOQOL-BREF instrument in a group of Chilean older subjects living in Metropolitan Santiago. MATERIAL AND METHODS: A linguistic-cultural adaptation of the Spanish version of the WHOQOL-BREF was performed and tested in a pilot study. Subsequently, the modified scale was applied to a group of 1186 older women aged 72 +/- 8 years and 334 men aged 72 +/- 7 years. The psychometric properties such as internal consistency, item-total correlation of responses, and construct validity were evaluated. A confirmatory factor analysis was done to check if the dimensions described in the original version, were evaluated. Analyses were performed with STA-TA statistical software 10.0 and LISREL 8.50. RESULTS: Confirmatory factor analysis confirmed that the dimensions physical health, psychological, social relationships and environment, described by the authors in their original description, were maintained. The instrument had a good internal consistency with a Cronbach alpha of 0.88 for the total scale and ranging from 0.70 to 0.79 in each of the dimensions. CONCLUSIONS: The evaluated version of the WHOQOL-BREF has an acceptable reliability and validity, and suggests that it is suitable for the assessment of Quality of Life in elderly people in Chile. PMID- 22051708 TI - [Silent celiac disease among 21 patients with cryptogenic epilepsy]. AB - BACKGROUND: Celiac disease (CD) is predominant in women and young people. Atypical, non-enteric symptoms are more common among adults. There is also an association between CD and neurological disorders, especially with cerebellar ataxia, polyneuropathy and epilepsy. AIM: To study the frequency of CD in a group of adults with cryptogenic epilepsy. MATERIAL AND METHODS: Twenty one patients with cryptogenic epilepsy, aged 20 to 65 years (14 women) were studied, measuring IgA-anti transglutaminase antibodies and deamidated gliadin peptide (DGP) IgG and IgA antibodies. RESULTS: One patient had elevated titers of both types of antibodies. Small bowel biopsy showed villous atrophy and lymphocytic infiltration compatible with CD. CONCLUSIONS: One of 21 adult patients with cryptogenic epilepsy had a silent CD. PMID- 22051709 TI - [Evaluation of the program for detection and treatment of depression in Chilean primary health care centers]. AB - BACKGROUND: Depression is highly prevalent among Chilean adults, therefore a primary care treatment program was devised. AIM: To evaluate the Program for detection, diagnosis and integral treatment of depression, implemented in Chilean Primary Health Care Centers. MATERIAL AND METHODS: A three and six months follow up study was conducted among women admitted to the program at seven primary health care centers in two regions of Chile. Socio-demographic data, treatments provided and compliance with the program were assessed. A clinical standardized interview (with ICD-10) was carried out and the intensity of depressive symptoms was evaluated using Beck Depression Inventory (BDI). RESULTS: The initial sample was composed by 201 women aged 25 to 65 years. At 6 months, 35% were lost from follow up. Depression was mild, moderate or severe in 12, 63 and 25% of women, respectively. The severity of depression was underestimated by primary care teams. Among women with regular and irregular attendance to medical appointments and those that abandoned treatment, BDI score decreased by 35, 37 and 13%, respectively. CONCLUSIONS: This primary care program for depression was effective to reduce BDI scores. Diagnostic precision of primary care teams must be improved. PMID- 22051710 TI - [Risk of attention deficit/hyperactivity disorder in Aymara and Rapa-Nui school children: association with dopaminergic system polymorphisms]. AB - BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness or inattentiveness. AIM: To search for differences in risk for ADHD and its components among Chilean native and mixed populations and to look forpossible associations with dopamine receptor D4 (DRD4) and dopamine transporter 1 (DAT1) polymorphisms. MATERIAL AND METHODS: School teachers were requested to complete the Conners test, which uses DSM-IV criteria, to screen for ADHD risk among Aymara and Rapa-Nui students. RESULTS: Rapa-Nui children from Easter Island had the highest risk of hyperactivity/impulsiveness. Aymara children from the Arica-Parinacota Region had lower scores. Although inattentiveness scores had lower differences between groups, overall ADHD score differences among studied populations were highly significant. DRD4 and DAT1 alleles had a heterogeneous distribution. Easter islanders had more divergent frequencies, mostprobably as a result of separate migration routes utilized at different timeperiods during the colonization of America and Polynesia. CONCLUSIONS: The comparison of ADHD risk parameters between Rapa-Nui and Aymara children showed marked differences. Allele distri-bution of dopamine polymorphisms in Easter Island was also significantly different from northern Chile, due probably to different colonization histories. These findings suggest that higher ADHD risk scores in Easter Island children may be linked to the presence of different DRD4 alleles. PMID- 22051711 TI - [Association between body mass index (BMI) and height from birth to 5 years in Chilean preschool children]. AB - BACKGROUND: It has been shown that excess weight gain during childhood is associated with a greater risk of obesity; this relationship may be mediated by growth in height. AIM: To quantify the associations between z scores for body mass index (BMIZ) and height for age (HAZ) from birth to 5 years of age and to assess how this association varies according to age and adiposity. MATERIAL AND METHODS: Weight and height were recorded at 11 occasions from birth on a cohort of 1089 Chilean five year-old children with a birth weight > 2500 g. BMI, BMIZ, HAZ and prevalence of obesity were calculated. We determined the cross-sectional association between BMIZ and HAZ for the total sample and by 3 BMI Z categories, using Pearson correlation. We determined the probability of obesity according to four HAZ categories. RESULTS: Obesity increased continuously reaching approximately 16% at 5 years. Stunting was virtually nonexistent. No association between BMIZ and HAZ was observed at birth, while at 1 and 2 months, leaner infants had lower stature. No association between these parameters was observed between 6-24 months, while after 3 years, a clear relationship was observed. CONCLUSIONS: The probability of a preschool child of being obese is less than 10% with a HAZ is < 0. Nevertheless, children with heights above the median (even within the normal range) have an increased risk of obesity, especially after 3 y of age. Between 0-5 years, the relationship between weight and height varies by age and adiposity. PMID- 22051712 TI - [Evaluation of embryotoxicity of misoprostol using the whole embryo culture assay]. AB - BACKGROUND: Approximately 15% of misoprostol-induced-abortions may not be successful, leading to in utero exposure to the drug and to the induction of a series of defects including central nervous system, limb and visceral defects. A common proposal is that the drug causes disruption of the fetal vasculature leading to embryonic or fetal hypoxia. AIM: To evaluate the teratogenicity of misoprostol using the rat post-implantation embryo culture. MATERIAL AND METHODS: Rat embryos were collected at the beginning of organogenesis and cultured in rat serum containing misoprostol at concentrations of 200, 2,000 or 20,000 pg/ml. Functionality, morphology and morphometry parameters were evaluated. RESULTS: Misoprostol induced a dose-dependent embryotoxic effect causing a decrease in embryo viability and function (poor vascular development and survival) and morphometry (alterations in branchial arches, heart and cephalic portions of the neural tube, among others). CONCLUSIONS: All the manifestations observed are indicative of the ability of misoprostol to directly induce developmental retardation and alterations. PMID- 22051713 TI - [Lifestyles and quality of life of post menopausal women]. AB - BACKGROUND: During menopause the quality of life of women can be seriously deteriorated and influenced by lifestyles. AIM: To assess the prevalence of menopausal symptoms and their relationship with lifestyles and quality of life. MATERIAL AND METHODS: The Menopause Rating Scale (MRS), a survey that measures menopausal symptoms and has questions related to lifestyles, was applied to 1023 women aged 54 +/- 6 years (range 45 to 64 years), consulting in primary health care clinics. A multiple linear regression analysis was used to evaluate the association between menopausal symptoms and lifestyle. RESULTS: Fifty six percent of women did not have a paid work, 64% were nonsmokers and 90% did not perform any physical exercise. The most frequent menopausal symptoms referred were muscle and joint ailments (85%) followed by mental and physical exhaustion (80%). Sedentary women, smokers or those who did not to have time for leisure activities showed worst quality of life scores. CONCLUSIONS: Postmenopausal women with unhealthy lifestyles had the lower quality of life scores and more menopausal symptoms. PMID- 22051714 TI - [Effectiveness of an educational program about the Chilean AIDS law in primary care health workers]. AB - BACKGROUND: In Chile, members of the civil society and government achieved the passing of the HIV/AIDS Law (19.779). The level of knowledge of the law held by healthcare workers in Chile is not well known. AIM: To analyze the effect of an intervention on knowledge of the existence of the law and its application in clinical practice among primary healthcare workers in southeastern Santiago. MATERIAL AND METHODS: Healthcare workers of primary care centers were invited to participate in the study. One group received an educational intervention lasting a total of 16 hours, about AIDS physiopathology, sexually transmitted diseases, communication with patients and current legislation. A control group did not receive the educational intervention. Both groups answered a self-administered questionnaire about the HIV/AIDS law at baseline and three months after the intervention. RESULTS: The intervention was carried out in 262 workers and 293 participated as controls. The initial evaluation revealed that only 16.3% (n = 89) had heard of the law, without any significant difference between intervention and control groups. The knowledge about the law improved by 65% in the intervention group and did not change in controls. At the end of the education period, the intervention and control groups improved their global knowledge by 29 and 3%, respectively (p < 0.05). CONCLUSIONS: The educational intervention was effective in improving knowledge of the HIV/AIDS Law among Chilean healthcare workers. PMID- 22051715 TI - Familial benign chronic pemphigus (Hailey-Hailey Disease): use of topical immunomodulators as a modern treatment option. AB - Benign chronic familial pemphigus (Hailey-Hailey disease) is a rare autosomal dominant blistering skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. The Hailey brothers first described it in 1939. Hailey-Hailey disease usually appears in the third or fourth decade, although it can occur at any age. Heat, sweating and friction often exacerbates the disease, and most patients have worse symptoms during summer. It is characterized clinically by a recurrent eruption of vesicles and bullae at the sites of friction and intertriginous areas. We report a 51-year-old male presenting with grey-brown hyperkeratosis with partial papillomatosis and lichenification in the axillary and inguinal areas and infiltrated erythematous lesions in the infraorbitary region, on the side of the face. Biopsies obtained from inguinal and axillar areas revealed parakeratotic crusts overlying an acantholytic epidermis. A biopsy from one of the lesions from the infraorbital area showed a Jessner-Kanof lymphocytic infiltration. The patient was treated with antimicrobials and four days later, topical Pimecrolimus was started, leading to an improvement of the clinical picture. The efficacy of Pimecrolimus in our case suggests that cellular immunity could play a role in the pathogenesis of Hailey Hailey disease. PMID- 22051716 TI - [Cognitive impairment associated to primary hyperparathyroidism: report of one case]. AB - We report a 79-year-old male patient presenting with progressive memory loss associated with anxiety and muscular pain. An extensive biochemical control revealed high serum calcium and parathormone levels, and normal thyroid hormones. Cognitive assessment prior to surgery was compatible with mild cognitive impairment, showing significant improvement two months after parathyroidectomy. Our case suggests that, although rare, primary hyperparathyroidism should be considered as a possible cause of cognitive decline in the elderly. PMID- 22051717 TI - [Euthanasia and medical act]. AB - Right to life -as the prohibition of intentionally and arbitrarily taking life, even with authorization of the concerned one- is an internationally recognized right. In many countries, debate regarding euthanasia is more centered in its convenience, social acceptability and how it is regulated, than in its substantial legitimacy. Some argue that euthanasia should be included as part of clinical practice of health professionals, grounded on individual's autonomy claims-everyone having the liberty to choose how to live and how to die. Against this, others sustain that life has a higher value than autonomy, exercising autonomy without respecting the right to life would become a serious moral and social problem. Likewise, euthanasia supporters some-times claim a 'right to live with dignity', which must be understood as a personal obligation, referred more to the ethical than to the strictly legal sphere. In countries where it is already legalized, euthanasia practice has extended to cases where it is not the patient who requests this but the family or some healthcare professional, or even the legal system-when they think that the patient is living in a condition which is not worthy to live. Generalization of euthanasia possibly will end in affecting those who need more care, such as elder, chronically ill or dying people, damaging severely personal basic rights. Nature, purpose and tradition of medicine rule out the practice of euthanasia, which ought not be considered a medical act or legitimately compulsory for physicians. Today's medicine counts with effective treatments for pain and suffering, such as palliative care, including sedative therapy, which best preserves persons dignity and keeps safe the ethos of the medical profession. PMID- 22051718 TI - [To kill, let die and euthanasia in the bill of rights of patients and in the Chilean doctrine]. AB - The Bill of Rights for Patients provides the patient with autonomy for disposing of his life, enabling him to reject those treatments that unnecessarily prolong his life. However, the bill does not allow an artificial acceleration of death. Therefore, the bill does not permit euthanasia (at least, certain form of it) nor assisted-suicide. However, according to the practice of medicine and also Chilean doctrine, it is permitted to inject morphine to a patient to relieve his pain, even though that could hasten his death. In consequence, it is allowed for the patient to dispose of his life and also to inject in him morphine for pain relief, endangering his life, but neither euthanasia nor assisted-suicide is allowed. Is this coherent? According to Chilean doctrine, it could be coherent under the condition of accepting the distinction between killing and letting die and also the double effect doctrine. The problem is that there is abundant English literature in the realm of moral philosophy to disregard both conditions. Therefore, it is possible to claim that the Bill is not coherent and that the Chilean doctrine is based upon a distinction and a doctrine that are not acceptable. PMID- 22051719 TI - [Bone allografts and the functions of bone banks]. AB - The use of bone grafts is a common practice in musculoskeletal surgery to provide mechanical stability where there is a defect and it allows skeletal reconstruction. Classically auto and allografts have been used. The latter are the choice in large, complex defects. Allografts can be transplanted despite cell death, have osteoconduction and osteoinduction capacity, low antigenicity and biomechanical properties similar to the original bone. They can be obtained from living and death donors. They are stored by cryopreservation and lyophilization in entities called bone banks. This is a review about bone allografts and the organization and function of the bone banks. PMID- 22051720 TI - [Malpractice in health care teams]. AB - To be successful, modern medical acts require the participation of several professionals and assistants and, as such, there has been a steady trend from individual medicine to the collective practice of the profession. This format raises issues in determining when a medical professional or other practitioner is liable for the acts of a colleague. This thesis proposes to resolve the problems involved in the collective practice of medicine by restricting liability to a physician responsible for another practitioner, only to those cases where he/she has been willingly introduced into the medical act. PMID- 22051721 TI - [Applying results from studies on diagnostic tests]. PMID- 22051724 TI - [Endovascular surgery as treatment for multiple sclerosis]. PMID- 22051725 TI - [How to face the increased prevalence of individual health-risk behaviours in Chile?]. PMID- 22051726 TI - Audiotactile integration is reduced in congenital blindness in a spatial ventriloquism task. AB - In the ventriloquism effect, the presentation of spatially discrepant visual information biases the localization of simultaneously presented sounds. Recently, an analogous spatial influence of touch on audition has been observed. By manipulating hand posture, it has been demonstrated that this audiotactile ventriloquist effect predominantly operates in an external frame of reference. In the present study, we examined the contribution of developmental vision to audiotactile interactions as indicated by the ventriloquism effect. Congenitally blind, late blind and sighted adults were asked to report the perceived location of sounds presented from a left, a central or a right location. Auditory stimuli were either delivered alone or concurrently with touches at the left or the right hand. The hands were located to the right and to the left of the lateral speakers and participants either adopted an uncrossed or a crossed hand posture. While sighted controls and late blind participants similarly mislocalized auditory stimuli toward the concurrent tactile stimuli in bimodal trials, the congenitally blind showed a reduced ventriloquism effect. All groups showed a reduced audiotactile ventriloquism effect in the crossed hand condition. However, the magnitude of the reduction was significantly larger in the group of congenitally blind than in the group of sighted controls. These results suggest reduced audio tactile interactions in spatial processing following a lack of visual input from birth. PMID- 22051729 TI - A biomechanical comparison of a novel thoracic screw fixation method: transarticular screw fixation vs traditional pedicle screw fixation. AB - BACKGROUND: Transarticular screw fixation is used in the upper cervical and lumbar spine to achieve posterior spinal stability, and its biomechanical performance has been proven to be similar to that of pedicle screw fixation. However, few studies have reported the use of transarticular screw fixation in the upper thoracic spine. OBJECTIVE: To biomechanically compare transarticular screws with pedicle screws in short-term cyclic loading in the upper thoracic spine. METHODS: Eight fresh human cadaveric spine specimens (T1-T3) were harvested and tested for 6 cycles in flexion, extension, lateral bending, and torsion in their intact condition. Each specimen was then destabilized and restabilized with 3 fixation methods: the pedicle screw/rod construct, the transarticular screw/rod construct, and transarticular screws alone. The instrumented specimens were reteted with the same protocol. RESULTS: All fixation systems reduced the range of motion significantly with respect to flexion, extension, lateral bending, and axial rotation (P < .01). However, no significant difference was observed between the 3 instrumented groups. CONCLUSION: This biomechanical study demonstrates in vitro that transarticular screws and pedicle screws have statistically similar biomechanical stability in a noncorpectomy model. Posterior transarticular screws may be an alternative for internal fixation in the upper thoracic spine. PMID- 22051730 TI - Identification of oncostatin M as a JAK2 V617F-dependent amplifier of cytokine production and bone marrow remodeling in myeloproliferative neoplasms. AB - The JAK2 mutation V617F is detectable in a majority of patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Enforced expression of JAK2 V617F in mice induces myeloproliferation and bone marrow (BM) fibrosis, suggesting a causal role for the JAK2 mutant in the pathogenesis of MPNs. However, little is known about mechanisms and effector molecules contributing to JAK2 V617F-induced myeloproliferation and fibrosis. We show that JAK2 V617F promotes expression of oncostatin M (OSM) in neoplastic myeloid cells. Correspondingly, OSM mRNA levels were increased in the BM of patients with MPNs (median 287% of ABL, range 22-1450%) compared to control patients (median 59% of ABL, range 12-264%; P < 0.0001). OSM secreted by JAK2 V617F+ cells stimulated growth of fibroblasts and microvascular endothelial cells and induced the production of angiogenic and profibrogenic cytokines (HGF, VEGF, and SDF-1) in BM fibroblasts. All effects of MPN cell-derived OSM were blocked by a neutralizing anti-OSM antibody, whereas the production of OSM in MPN cells was suppressed by a pharmacologic JAK2 inhibitor or RNAi-mediated knockdown of JAK2. In summary, JAK2 V617F-mediated up-regulation of OSM may contribute to fibrosis, neoangiogenesis, and the cytokine storm observed in MPNs, suggesting that OSM might serve as a novel therapeutic target molecule in these neoplasms. PMID- 22051731 TI - Phenotypic heterogeneity in Chinese patients with hepatocyte nuclear factor-1beta mutations. AB - AIMS/HYPOTHESIS: The aim of this study was to investigate clinical spectrum of hepatocyte nuclear factor-1beta (HNF-1beta) mutation in Chinese diabetic patients with renal dysfunction and/or structure abnormalities. MATERIALS AND METHODS: A total of 104 diabetic patients with renal structural abnormalities and/or non diabetic renal dysfunction were recruited and HNF-1beta mutation was screened by direct sequencing. RESULTS: Three heterozygous missense mutations including c.494G>A (p.R165H), c.662A>T (p.D221V) and c.780G>C (p.E260D) were identified. Progression of diabetes and mild decline of renal function were observed in the mutation carriers during the follow-up. The p.R165H mutation carrier had severe beta-cell dysfunction and different extrapancreatic phenotypes. Compared with type 2 diabetes and normoglycemics, the p.R165H mutation carrier had a lower basal C-peptide (0.30, 0.61+/-0.07 and 0.50+/-0.04 nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively) and low values of acute C-peptide response to arginine (0.15, 0.48+/-0.18 and 0.76+/-0.08 nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively). CONCLUSION: Patients with the HNF 1beta mutation in our population can have different pancreatic and extrapancreatic phenotypes. The exact contributions of mutations to the phenotypes await functional confirmation. PMID- 22051732 TI - Simultaneous high speed optical and impedance analysis of single particles with a microfluidic cytometer. AB - We describe a microfluidic cytometer that performs simultaneous optical and electrical characterisation of particles. The microfluidic chip measures side scattered light, signal extinction and fluorescence using integrated optical fibres coupled to photomultiplier tubes. The channel is 80 MUm high and 200 MUm wide, and made from SU-8 patterned and sandwiched between glass substrates. Particles were focused into the analysis region using 1-D hydrodynamic focusing and typical particle velocities were 0.1 ms(-1). Excitation light is coupled into the detection channel with an optical fibre and focused into the channel using an integrated compound air lens. The electrical impedance of particles is measured at 1 MHz using micro-electrodes fabricated on the channel top and bottom. This data is used to accurately size the particles. The system is characterised using a range of different sized polystyrene beads (fluorescent and non-fluorescent). Single and mixed populations of beads were measured and the data compared with a conventional flow cytometer. PMID- 22051733 TI - Preoperative spirometry results as a determinant for long-term mortality after EVAR for AAA. AB - OBJECTIVES: The aim of this study was to analyse lung function test determinants for long-term mortality after standard endovascular aneurysm repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA). DESIGN: Retrospective analysis. MATERIALS: Three-hundred and four consecutive patients treated electively with EVAR (Zenith((r)) stent grafts, Cook) between May 1998 and February 2006 were prospectively enrolled in a computerised database. METHODS: The Global Initiative for Chronic Obstructive Lung Diseases (GOLD) guideline was used to grade the severity of obstructive lung disease. Mortality was checked until 1 December 2010. Median follow-up time was 68 (interquartile range (IQR) 40-94) months. RESULTS: The percentage of patients with mild, moderate or severe (grade 3) chronic obstructive pulmonary disease (COPD) was 9.9%, 23.2% and 7.7%, respectively. In a combined medical severity assessment, arterial partial pressure of oxygen (PaO(2)) < 8.0 kPa or COPD, grade >=3 (hazard ratio (HR) 2.06; 95% confidence interval (CI) (1.24-3.42)), anaemia (HR 1.72; 95% CI (1.21-2.44)), chronic kidney disease, stage >=3 (HR 1.55; 95% CI (1.08-2.24)) and age >=80 years (HR 1.55; 95% CI (1.04-2.31)) were independently associated with long-term mortality. Lower forced expiratory volume in 1 s (FEV(1)) (p = 0.002) and lower forced vital capacity (FVC) (p = 0.003) were independently associated with long term mortality. CONCLUSIONS: Our findings strengthen the need for formal evaluation of lung function with spirometry prior to proceeding to AAA repair. PMID- 22051734 TI - The EORTC 10041/BIG 03-04 MINDACT trial is feasible: results of the pilot phase. AB - BACKGROUND: The MINDACT (Microarray In Node-negative and 1-3 node positive Disease may Avoid ChemoTherapy) trial investigates the clinical utility of the 70 gene profile (MammaPrint) for the selection of breast cancer patients for adjuvant chemotherapy (CT) together with standard clinicopathological criteria. We present the results of the pilot phase consisting of first 800 patients included. METHODS: MINDACT has enrolled 6600 patients, classified into high or low risk by MammaPrint and clinicopathological risk through Adjuvant! Online. Patients with both clinical (C) and genomic (G) high risks are offered adjuvant CT; those with both C and G low risks do not receive CT; patients with discordant risk are randomised for the decision of adjuvant CT based on C or G risk. CT randomisation of anthracycline-based versus docetaxel/capecitabine and endocrine therapy randomisation between letrozole and tamoxifen->letrozole are offered. RESULTS: During the pilot phase 46% of screened patients were enrolled. Main reasons for non-enrolment were node positivity before trial amendment, sample quality problems and failure to meet logistic settings. Among the 800 patients, 386 (48%) were C-low/G-low, 198 (24.8%) as C-high/G-high, 75 (9.4%) as C-low/G high and 141 (17.6%) as C-high/G-low. In total 216 (27%) cases were discordant. The difference between patients with C-high (42%) and G-high risk (34%) is 8.25% (95% confidence interval (CI), 4.7-11.8%; P<.0001). Compliance with the treatment decision was high (>92%). CONCLUSIONS: The logistically complex MINDACT trial is feasible in a multinational setting. The proportion of discordant patients, the potential reduction in CT by using the genomic signature and compliance to treatment assignment are in accordance with the trial hypotheses. PMID- 22051735 TI - Rare cancers of the head and neck area in Europe. AB - The RARECARE project has proposed a different and more detailed grouping of cancers, based on localisation and histological type, in order to identify rare entities with clinical meaning. RARECARE gathered data on cancer patients diagnosed from 1978 to 2002 and archived in 76 population-based cancer registries, all of which had vital status information available up to at least 31st December 2003. This study provides incidence, prevalence and survival rates for rare head and neck epithelial (H&N) cancers. Among the rare H&N cancers, those of oral cavity had the highest annual crude incidence rate of 48 per million, followed by oropharynx and 'major salivary glands and salivary gland type tumours' (28 and 13 per million, respectively). Incidence rates of epithelial tumours of nasal cavities, nasopharynx, eye and adnexa and middle ears were all lower than 5 per million. The prevalence for all investigated entities was lower than 35 per 100,000. The 5-year relative survival rates ranged from 40% for epithelial cancer of oropharynx to 85% for epithelial cancer of eye and adnexa. Survival rates were lower for men and for patients aged >=65 years. With few exceptions, the lowest and highest survival figures were observed for Eastern Europe and Northern Europe, respectively. According to the definition for rare tumours by RARECARE (incidence<6 per 100,000), as well as according to the definition for rare diseases by the European Commission (prevalence<50 per 100,000) the H&N cancers described in this paper should be considered rare and diagnosis and treatment of these cancers should therefore be centralised. PMID- 22051736 TI - Association between 11 genetic polymorphisms in folate-metabolising genes and head and neck cancer risk. AB - Genetic polymorphisms in folate metabolism may affect the risk of head and neck cancer (HNSCC) due to its involvement in DNA methylation and synthesis. We conducted a case-control study (265 HNSCC cases and 466 non-cancer controls) to investigate associations of MTHFR C677T and A1298C, MTR A2756G, MTRR A66G, RFC1 A80G, MTHFD1 G1958A, CBS 844ins68, TC2 C776G and A67G, SHMT C1420T and BHMT G742A polymorphisms with HNSCC risk. Interactions between polymorphisms and survival time, tobacco and alcohol habits, age, gender and tumour staging (TNM classification) were evaluated by multiple logistic regression analysis. We found that age >= 49 years (P<0.001), male gender (P=0.03), tobacco habit (P<0.001), MTHFR 1298AC/CC (P=0.028), MTR 2756AG/GG (P=0.010) and RFC1 80AG/GG (P=0.015) genotypes were associated with an increased risk of HNSCC. There were interactions between lower survival and CBS 844ins68 (P=0.005); age >= 49 years and MTR 2756 AG/GG (P=0.004) and RFC1 80AG/GG (P=0.006) genotypes; male gender and MTHFR 1298 AC/CC (P=0.030), MTR 2756 AG/GG (P=0.006) and RFC1 80 AG/GG (P=0.009); tobacco non-habit and MTHFD1 1958GA/AA (P=0.040); tobacco and MTHFR 1298 AC/CC (P=0.054) and MTR 2756 AG/GG (P=0.010); alcohol non-consume and RFC1 80 AG/GG (P=0.008) with HNSCC increased risk. MTHFR C677CT/TT genotypes were less frequently in advanced tumours (P=0.04). In conclusion, our data provide evidence that folate metabolism genetic polymorphisms associated with variables as advanced age, male gender, tobacco and alcohol increase HNSCC development; CBS 844ins68 and MTHFR C677T polymorphisms are associated with less survival time and advanced stage tumours, respectively. PMID- 22051737 TI - A sensitive graphene oxide-DNA based sensing platform for fluorescence "turn-on" detection of bleomycin. AB - A sensitive and selective fluorescent sensing platform for bleomycin (BLM) was developed based on BLM-induced DNA strand scission and the difference in affinity of graphene oxide for single-stranded DNA containing different numbers of bases in length. PMID- 22051738 TI - Prevention of cervical cancer in women's hands: Mexico leads the way. PMID- 22051739 TI - Self-collection of vaginal specimens for human papillomavirus testing in cervical cancer prevention (MARCH): a community-based randomised controlled trial. AB - BACKGROUND: Vaginal self-sampling for human papillomavirus (HPV) DNA testing could increase rates of screening participation. In clinic-based settings, vaginal HPV testing is at least as sensitive as cytology for detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse; however, effectiveness in home settings is unknown. We aimed to establish the relative sensitivity and positive predictive value for HPV screening of vaginal samples self-collected at home as compared with clinic-based cervical cytology. METHODS: We did a community-based, randomised equivalence trial in Mexican women of low socioeconomic status aged 25 65 years. Participants came from 540 medically underserved, predominantly rural communities in Morelos, Guerrero, and the state of Mexico. Our primary endpoint was CIN 2 or worse, detected by colposcopy. We used a computer-generated randomisation sequence to randomly allocate patients to HPV screening or cervical cytology. Eight community nurses who were masked to patient allocation received daily lists of the women's names and addresses, and did the assigned home visits. We referred women with positive results in either test to colposcopy. We did per protocol and intention-to-screen analyses. This trial was registered with the Instituto Nacional de Salud Publica, Mexico, INSP number 590. FINDINGS: 12,330 women were randomly allocated to HPV screening and 12,731 to cervical cytology; 9202 women in the HPV screening group adhered to the protocol, as did 11,054 in the cervical cytology group. HPV prevalence was 9.8% (95% CI 9.1-10.4) and abnormal cytology rate was 0.38% (0.23-0.45). HPV testing identified 117.4 women with CIN 2 or worse per 10,000 (95.2-139.5) compared with 34.4 women with CIN 2 or worse per 10,000 (23.4-45.3) identified by cytology; the relative sensitivity of HPV testing was 3.4 times greater (2.4-4.9). Similarly, HPV testing detected 4.2 times (1.9-9.2) more invasive cancers than did cytology (30.4 per 10,000 [19.1-41.7] vs 7.2 per 10,000 [2.2-12.3]). The positive predictive value of HPV testing for CIN 2 or worse was 12.2% (9.9-14.5) compared with 90.5% (61.7-100) for cytology. INTERPRETATION: Despite the much lower positive predictive value for HPV testing of self-collected vaginal specimens compared with cytology, such testing might be preferred for detecting CIN 2 or worse in low-resource settings where restricted infrastructure reduces the effectiveness of cytology screening programmes. Because women at these sites will be screened only a few times in their lives, the high sensitivity of a HPV screen is of paramount importance. FUNDING: Instituto Nacional de Salud Publica, the Health Ministry of Mexico, QiAGEN Corp. PMID- 22051741 TI - Cavity optomechanics: Mechanical memory sees the light. PMID- 22051742 TI - Nanoelectronics: Shuttle transport for single electrons. PMID- 22051743 TI - Nanomedicine: Gold nanowires to mend a heart. PMID- 22051744 TI - Nanoparticle devices: Going with the electron flow. PMID- 22051745 TI - Survival rates of implants inserted in the maxillary sinus area by internal or external approach. AB - OBJECTIVE: There are 2 surgical techniques to elevate the sinus floor: sinus lift with crestal approach (internal sinus lift [ISL]) and sinus lift with lateral wall approach (external sinus lift [ESL]). The aim of this study was to evaluate and compare the survival rates of implants placed in the posterior maxilla with ESL or ISL. PATIENTS AND METHODS: Ninety sinus lifts with lateral wall approach were performed in 82 patients, and 147 implants were inserted in these augmented sinuses in ESL group. Forty-five implants were inserted in maxilla in 33 patients with sinus lift with crestal approach in ISL group. The follow-up time was 33.8 and 15.6 months for ESL and ISL groups, respectively. RESULTS: One implant failure was observed in ESL group, and there was no implant failure in ISL group. All other implants were functioning well without any significant clinical finding. Implant survival was 99.2% in ESL group and 100% in ISL group. CONCLUSION: The sinus lift with lateral wall approach and crestal approach were reliable methods for implant insertion in the posterior maxilla. Survival rates of the ISL were slightly higher than ESL group. However, follow-up time of the ISL was shorter. PMID- 22051746 TI - Predictive value of different HDL particles for the protection against or risk of coronary heart disease. AB - The inverse relationship between plasma HDL levels and the risk of developing coronary heart disease is well established. The underlying mechanisms of this relationship are poorly understood, largely because HDL consist of several functionally distinct subpopulations of particles that are continuously being interconverted from one to another. This review commences with an outline of what is known about the origins of individual HDL subpopulations, how their distribution is regulated, and describes strategies that are currently available for isolating them. We then summarise what is known about the functionality of specific HDL subpopulations, and how these findings might impact on cardiovascular risk. The final section highlights major gaps in existing knowledge of HDL functionality, and suggests how these deficiencies might be addressed. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945 2010). PMID- 22051747 TI - Severe mitral regurgitation secondary to dehiscence of a mitral annuloplasty ring shown on 3D transoesophageal echocardiography. PMID- 22051748 TI - [Compliance with Chilean diagnostic guidelines among patients with ischemic stroke admitted to a public hospital]. AB - BACKGROUND: Acute ischemic stroke in adults was given an Explicit Guarantee of diagnosis and treatment (GES) with Clinical Guidelines in 2007 as part of the on going Chilean National Health Reform. AIM: To evaluate the adherence to official guidelines with regard to the use of diagnostic methods for patients with acute ischemic stroke during their stay in a public hospital. PATIENTS AND METHODS: The study included a review of the medical records of 101 patients aged 70 +/- 13 years (49 males and 52 females) diagnosed with acute ischemic stroke and discharged within August and September of 2008 and 2009 from a public hospital. Three trained observers independently determined the degree of dependency of patients at discharge using the Modified Rankin score. The completion of recommended diagnostic tests (electrocardiogram, carotid Doppler ultrasound and echocardiogram) as well as their overuse was evaluated. RESULTS: Ten patients died before discharge, 38% were discharged with and 52% were discharged without disabilities. Nineteen percent of patients with a Modified Rankin score of two or less (corresponding to a slight disability) had a complete diagnostic workup, compared with 87% of patients with a score of 3 to 5 (moderate to severe disability). In 27% of the patients, there was an overuse of diagnostic tests. No association between the diagnostic test use adequacy and year of discharge was observed. CONCLUSIONS: There exists a disparity between the recommended diagnostic testing and the actual tests completed among patients with acute ischemic stroke. PMID- 22051749 TI - [Results of treatment with peginterferon plus ribavirin in patients with chronic hepatitis C]. AB - BACKGROUND: The current treatment recommendation for chronic hepatitis C virus infection is the combination of peginterferon and ribavirin for 24 or 48 weeks, depending on the viral genotype. The aim of the therapy is to obtain a sustained virological response. AIM: To report our experience in the treatment of chronic hepatitis C. MATERIAL AND METHODS: Analysis of 52 patients treated between September 2000 and June 2009. Patients with genotype 1 or 5 were treated with peginterferon alpha 2a (180 ug/week) and ribavirin (1000 mg/day for those weighing less than 75 kg and 1200 mg/day for those weighing more than 75 kg) during 48 weeks. Patients with genotypes 2 and 3 were treated for 24 weeks with the same dose of peginterferon and ribavirin 800 mg/day. RESULTS: Viral genotypes 1, 2, 3 and 5 were present in 81, 4, 11 and 4% of patients, respectively. Twenty four patients (46 %), 18 with genotype 1, achieved a sustained viral response. Age was the only variable that influenced the response to treatment. CONCLUSIONS: Approximately half of the patients with chronic hepatitis C, achieve a sustained viral response with peginterferon and ribavirin. PMID- 22051750 TI - [Combined influence of preconception body mass index and gestational weight gain on fetal growth]. AB - BACKGROUND: The Chilean Ministry of Health has been using standards for nutritional evaluation and weight gain recommendations during pregnancy in the last 25 years. In the meantime new standards have been developed. AIM: To study the combined influence of preconception maternal nutritional status and gestational weight gain, using new standards to classify those parameters, on perinatal outcomes. MATERIAL AND METHODS: A cohort of 11,465 healthy pregnant women was prospectively followed until term. Their pre-gestational nutritional status was classified using the body mass index cut-offs in use in the United States (USA). Their gestational weight gain was classified using categories proposed in a Danish study. Perinatal outcomes included were risky birth weight, i.e. < 3000 g and >= 4000 g, and cesarean delivery. Relative risks for those perinatal outcomes were calculated for all combined categories of pre-gestational nutritional status and gestational weight gain. RESULTS: Relative risks of almost all gestational weight gain results were statistically significant for women having a normal pre-gestational nutritional status meanwhile all of them were not significant for underweight women. Overweight and obese women had similar relative risks values as normal women. However, many of them were not significant, especially in obese women. CONCLUSIONS: There is an independent and combined influence of preconception nutritional status and gestational weight gain on perinatal outcomes, when using standards to classify those parameters developed in the USA and Denmark, respectively. PMID- 22051751 TI - [Association between atherosclerosis and periodontitis]. AB - BACKGROUND: Chronic inflammation and infections are involved in the development and progression of atherosclerotic vascular disease. AIM: To evaluate the association between periodontitis and early atherosclerosis. MATERIAL AND METHODS: Fifty-three subjects who received periodontal treatment and regular maintenance for at least 10 years, and 55 subjects with periodontitis but without a history of periodontal treatment were studied. Carotid artery intima-media wall thickness (CIMT) was measured with high-resolution B-mode ultrasonography. A blood sample was obtained to measure high sensitivity C-reactive protein, fibrinogen, lipoprotein cholesterol, leukocyte count and erythrocyte sedimentation rate. Covariates included age, gender, smoking, level of education, body mass index and physical activity. The benzoyl-DL-arginine-naphthylamide (BANA) test was used to determine the number of periodontal sites with periodontal pathogens. RESULTS: CIMT value was significantly higher in subjects with periodontitis than those without it (0.775 +/- 0.268 and 0.683 +/- 0.131 mm respectively, p = 0.027). C-reactive protein, leukocyte count and percentage of sites with periodontal pathogens were also significantly higher in subjects with periodontitis. Regression analysis identified age, periodontitis, and smoking as independent predictors of CIMT. CONCLUSIONS: These results suggest that untreated periodontitis is associated with early atherosclerotic carotid lesions and higher levels of inflammatory markers. PMID- 22051752 TI - [Cross sectional geriatric assessment of Mexican older people]. AB - BACKGROUND: Due to the progressive aging of our population, it is imperative to evaluate the life conditions and health limitations of older people. AIM: To report the results of an integral geriatric evaluation of Mexican older people. MATERIAL AND METHODS: A cross-sectional assessment of 324 older subjects of a median age of 70 years (57% females) beneficiaries of the Mexican Institute of Social Security of the city of Queretaro. Social, demographic, medical, functional and cognitive variables were evaluated. RESULTS: Of the studied subjects, 37% were illiterate, 61% lived with a partner and 47% were dedicated to household activities. Thirty three percent had visual impairment, 54% had hearing impairment, 39% had urinary incontinence, 26% reported falls in the last six months, 34% had nutritional problems, 38% were functionally dependent, 49% had sleeping problems, 25% had cognitive impairment and 25% had depression. CONCLUSIONS: The general health outlook of this population is encouraging, considering that more than half are not functionally impaired. PMID- 22051753 TI - [Prevalence of metabolic syndrome in children and adolescents who consult with obesity]. AB - BACKGROUND: The higher prevalence of childhood obesity has led to search for metabolic syndrome (MS) in this age group. AIM: To study the prevalence of MS in obese children and adolescents. MATERIAL AND METHODS: Cross sectional study of 255 obese children and adolescents aged 11.3 +/- 2.4 years, 45% males, 60% pubertal, with a body mass index (BMI) z score of 2.7 +/- 0.6, who were evaluated for obesity. MS was defined as the presence of at least three of the following criteria, according to Ferranti: fasting glucose (FG) >= 100 mg/dl, triglycerides (TG) >= 100 mg/dl, HDL < 50 mg/dl, waist circumference (WC) > percentile (p) 75 and blood pressure (BP) > p90. Patients were also classified using Cook criteria: FG >= 100 mg/dl, TG >= 110 mg/dl, HDL < 40 mg/dl, WC > p 90, BP > p 90. RESULTS: MS was observed in 45 and 22.7% of patients, according to Ferranti and Cook definitions, respectively. WC was the most frequent criteria and glucose was the most uncommon. Males had higher body mass index, WC and TG levels than females. According to Ferranti and Cook definitions, MS prevalence was 53.5 and 28% in males and 37.6 and l8.4% in females (p < 0.05). Fifty and 26.1% of pubertal patients exhibited MS vs 36.9 and 17.5% in pre-pubertal subjects (p < 0.05) using Ferranti and Cook criteria, respectively. The frequency of MS increased along with a higher BMI. CONCLUSIONS: MS is a prevalent condition in obese children and adolescents, especially in males and pubertal children. It is necessary to have a better and universal definition for MS in pediatrics including all ages, in order to be focused in obesity prevention and treatment. PMID- 22051754 TI - [Vulnerability of pregnant women living in a community of Metropolitan Santiago]. AB - BACKGROUND: The program "Chile grows with you" is a part of the Chilean social protection system oriented to decrease social inequities from pregnancy (a socially secure pregnancy) to four years of age, directed to the poorest 40% of the population. AIM: To determine the incidence of social vulnerability and its determinants, starting at the gestation period. MATERIAL AND METHODS: Data was obtained from anonymous secondary data based on the records of the first assessment of pregnant women and from social protection surveys, provided by the Ministry of Planning and Cooperation. RESULTS: The incidence of social vulnerability was high. However there was a disparity between the figures obtained from the social protection records and the survey carried out during the first assessment of pregnant women (91 and 27% respectively). The psychosocial risk was higher among vulnerable women (42% compared to 28% among women not considered vulnerable). This risk was associated with lack of family support, depressive symptoms, gender violence, substance abuse and maternity conflicts. Working conditions were precarious with a low level of social security, there were habitability problems, disability, dependency, female householders and a mean income below the threshold of poverty. CONCLUSIONS: Among vulnerable families, there are adverse determinants that attempt against a socially secure pregnancy and integral development of children. PMID- 22051755 TI - Demographic characteristics in preeclamptic women in Macedonia. AB - BACKGROUND: Worldwide, pre-eclampsia and eclampsia contribute to the death of a pregnant woman every three minutes. AIM: To determine the demographic risk factors and values of blood pressure to predict preeclampsia. MATERIAL AND METHODS: Demographic and clinical features of 300 normotensive pregnant women aged 28 +/- 5 years and 100 preeclamptic women aged 28 +/- 6 years, were assessed. Women with multiple pregnancies were excluded from the study. RESULTS: Women with less educational attainment had a higher risk of mild and severe preeclampsia. Weight gain during pregnancy in control and pre eclamptic women were 14 +/- 3 and 20 +/- 5 kg, respectively (p < 0.01). Women with severe preeclampsia had high significantly shorter gestations then the other two patient groups (p < 0.01). Compared to normotensive women, at 6 to 12 weeks of gestation, pre eclamptic women had higher systolic (102 +/- 7 and 113 +/- 9 mmHg respectively), diastolic (64 +/- 5 and 74 +/- 10 mmHg respectively) and mean arterial pressure (77 +/- 5 and 87 +/- 8.01 mmHg respectively). CONCLUSIONS: Women with basic education or illiterate have a higher risk of developing preeclampsia. During the first or second trimester of pregnancy, mean arterial pressure is the best predictor for preeclampsia. PMID- 22051756 TI - [Effects on blood glucose of prophylactic dexamethasone for postoperative nausea and vomiting in diabetics and non-diabetics]. AB - BACKGROUND: Postoperative nausea and vomiting (PONV) prophylaxis with dexamethasone may produce significant hyperglycemia in the postoperative period. AIM: To evaluate if this effect is of greater severity in type 2 diabetics compared with non-diabetic patients. MATERIAL AND METHODS: Forty non-diabetic and thirty type 2 diabetic patients undergoing laparoscopic cholecystectomy were studied in a prospective and double-blind fashion manner. Patients were randomly distributed into 4 groups: Group I, non-diabetics control (n = 20), Group II, non diabetics dexamethasone (n = 20), Group III, type 2 diabetics control (n = 15), and Group IV, type 2 diabetics dexamethasone (n = 15). Immediately after induction, patients in groups I and III received isotonic saline and patients in the dexamethasone groups received 8 mg i.v. of the steroid. Capillary blood glucose concentrations were measured at baseline and every 2 hours during the first 12 hours since the start of surgery. A linear mixed effect model, adjusted for baseline capillary glucose concentration, age and duration of surgery was used to analyze the data. RESULTS: No effect of the presence of diabetes mellitus was observed in the evolution of glucose concentrations. There was a difference in capillary glucose concentrations between patients who received dexamethasone and placebo that started 2 hours post-intervention, reaching a mean maximum difference of 34 mg/dl (adjusted model, p < 0.001) at 10 hours post-intervention. CONCLUSIONS: In this study, Type 2 diabetic patients did not show a higher susceptibility than non-diabetics to develop postoperative hyperglycemia after the use of prophylactic dexamethasone for PONV. PMID- 22051757 TI - [Training of specialists in the Chilean national health services]. AB - Several institutions, such as the Ministry of Health, Universities, the Chilean Medical Association, Scientific societies and public opinion, recognize that there is a deficiency of specialized physicians in Chile. To overcome this shortage of specialists, the Ministry of Health, along with universities, is developing diverse initiatives to train specialists and cope with the requirements of the country. Seventy five percent of posts offered were filled by physicians. The number of positions increased from 173 in 2007 to 576 in 2010, with a cumulative total of 1582 physicians in four years. Fifty two percent are being trained in Basic Primary Specialties and 48% in primary specialties. Thirty three percent of graduates have the obligation to continue working in the public service during a certain lapse. This figure will increase to 50% in the following years. These specialists are mainly working in the more densely populated regions of the country. The universities that offer the higher number of training positions are the University of Chile, The Catholic University of Chile and the University of Santiago. PMID- 22051758 TI - [Primary left atrial hemangiopericytoma. Report of one case]. AB - We report a 41-year-old male presenting with progressive dyspnea lasting one month. A CAT scan disclosed a left atrial mass, that was surgically excised. The pathological study of the surgical piece showed a primary hemangiopericytoma. One month later, the patient consulted for cervical pain and a positron emission tomography showed multiple metastases. The patient died two months later. PMID- 22051759 TI - [Severe disseminated tuberculosis in a patient on immunosuppressive treatment. Report of one case]. AB - Patients on immunosuppressive therapy are at increased risk of developing tuberculosis. We report a 39-year-old female with an ulcerative colitis receiving prednisone, azathioprine and azulfidine that was admitted to hospital due to fever, anemia, diarrhea and hematochezia. A chest CT scan showed multiple miliary micronodular images diffusely distributed and mediastinal enlarged lymph nodes with central necrosis, suggestive of disseminated tuberculosis. Antituberculous treatment was started but discontinued and the patient was treated as a bronchiolitis obliterans with methylprednisolone pulses and discharged. She was readmitted in shock one week later and died. After her death cultures for Mycobacterium tuberculosis were informed as positive. The clinical picture of the patient is known as sepsis tuberculosa gravissima. PMID- 22051760 TI - [Herpes simplex virus type 1 as risk factor associated to Alzheimer disease]. AB - Herpes simplex virus type 1 (HSV-1) is ubiquitous, neurotropic, and the most common pathogenic cause of sporadic acute encephalitis in humans. Herpes simplex encephalitis is associated with a high mortality rate and significant neurological, neuropsychological, and neurobehavioral sequels. HSV-1 infects limbic system structures in the central nervous system (CNS), and has been suggested as an environmental risk factor for Alzheimer's disease. The possibility that HSV-1 reactivates in CNS neurons causing chronic progressive damage at cellular level and altering the neuronal functionality has not been thoroughly investigated. Currently it is ignored if recurrent reactivation of HSV 1 in asymptomatic patients involves some risk of progressive deterioration of the CNS functions caused, in example, by a neuroinflammatory response against the virus or by direct toxicity of the pathogen on neurons. Therefore, studies regarding the routes of dissemination of HSV-1 from the peripheral ganglions to the CNS, as well as the possible cellular and molecular mechanisms implied in generating neuronal damage during latent and productive infection, are of much relevance. PMID- 22051761 TI - [Coronary stents and non-cardiac surgery: current management strategies]. AB - The care of patients with coronary stents in the perioperative period of non cardiac surgery requires anesthesiologists, surgeons and cardiologists. The management of dual antiplatelet therapy should be handled depending on type and urgency of the surgery, the risk of bleeding, type of coronary stent implanted, time from placement and the risk of stent thrombosis. For patients identified as high risk of stent thrombosis, surgery should be planned at hospitals with cardiac catheterization facilities. These patients require postoperative monitoring and antiplatelet therapy should be restarted immediately. Stent thrombosis should be recognized early and treated aggressively with percutaneous coronary intervention. PMID- 22051762 TI - [Possible association between Mycobacterium avium subsp paratuberculosis infection and Crohn's disease]. AB - Paratuberculosis is a chronic intestinal disease of animals caused by Mycobacterium avium subsp. paratuberculosis (MAP), which has some pathological features similar to Crohn's disease (CD) in humans. The presence of MAP in food for human consumption and in affected tissues of patients with CD has been detected. Therefore, a causal association between this microorganism and the disease in humans, has been postulated. However, several related studies have failed to confirm this hypothesis and the scientific acceptance of MAP as a zoonotic agent remains controversial. This review presents the main findings related to this issue, contrasting evidences for and against an association between MAP and CD. The need to promote national studies focusing on this area is suggested. PMID- 22051763 TI - [Cholesteryl ester transfer protein inhibition in the management of atherosclerotic cardiovascular disease: second act "A rebirth of hope"]. AB - Despite the clinical use of statins to reduce serum levels of LDL cholesterol and treat atherosclerotic cardiovascular disease, a high proportion of patients remain at significant residual cardiovascular risk. In this context, low HDL cholesterol levels are an additional risk factor and intervention studies suggest that a fraction of the cardiovascular protection achieved with pharmacotherapy is explained specifically by the increase in serum levels of HDL cholesterol. Pharmacological inhibitors of the cholesteryl ester transfer protein (CETP) can induce a significant elevation in HDL cholesterol and, potentially, lead to better control of residual cardiovascular risk beyond the benefit demonstrated by statins. While the use of torcetrapib had unexpected side effects, dalcetrapib and anacetrapib are new CETP inhibitors with a better safety profile and are currently under study to evaluate their effects on vascular lesions and clinical events in patients at high cardiovascular risk. If these studies show positive findings, we will witness a new biomedical advance as significant as was the clinical. PMID- 22051764 TI - [Florence Nightingale (1820-1910), 101 years after her death]. AB - We herein describe Florence Nightingale's life and work. She is considered one of the pioneers in nursing practice. Her greatest success was during the Crimean war when, along with 38 voluntary nurses, she cleaned and refurbished the hospital in Scutari and reduced the mortality rate from 40 to 2%. She used to make rounds at night in the wards under the light of a lamp, and therefore she was named "The Lady with the Lamp". Queen Victory gave her the Royal Red Cross and she was the first woman who was honored with the Order of Merit in 1907. She had solid knowledge on Statistics and Mathematics which were useful for her nursing job. PMID- 22051765 TI - [The teaching profession]. PMID- 22051766 TI - [Economic evaluation in health care in Chile: towards a broader framework]. PMID- 22051767 TI - [Importance of chain of custody of evidences]. PMID- 22051768 TI - [The length of hospital stay in patients with acute coronary syndrome is reduced by establishing a chest pain unit]. AB - BACKGROUND: Providing prompt and appropriate therapy, combined with the increased economic requirements of treating patients with acute coronary syndrome (ACS), places high demands on the emergency department. The aim of the present analysis is to evaluate to what extent establishing a dedicated chest pain unit (CPU) influences the length of hospital stay in ACS patients. METHODS: Patients presenting with suspected ACS between 05/2004 and 05/2006 to either the emergency department (ED) or the newly established CPU were retrospectively analyzed. The CPU became functional in July 2005. Data were obtained according to standardized procedures based on patient charts and all available clinical information. RESULTS: A total of 247 patients were treated in the ED and 765 in the CPU. In the ED patient group 29 (11.7%) were diagnosed with ST elevation myocardial infarction (STEMI), 38 (15.4%) with non-ST elevation myocardial infarction (NSTEMI) and 15 (6.1%) with unstable angina pectoris (UAP), while ACS could be excluded in 165 (66.8%) patients. Patients treated in the CPU showed a higher percentage of ACS with 75 (9.8%) STEMI, 128 (16.7%) NSTEMI and 136 (17.8%) UAP patients; ACS could be excluded in 426 (55.7%) patients. The median length of hospital stay was shorter in ACS patients treated in the CPU at 5.0 days compared to 8.0 days if admitted to the ED (p<0.001). No difference in length of hospital stay was observed in UAP patients, whereas in STEMI patients admitted to the ED the time was longer at 8.0 days compared to 7.0 days if admitted to the CPU (p=0.042). A reduction from 8.0 to 6.0 days in the length of hospital stay if admitted to the CPU compared to the ED could be observed (p=0.002) in NSTEMI patients. CONCLUSIONS: Establishing a chest pain unit with optimized diagnostic and structural processes is associated with reduced lengths of hospital stay in patients with ACS treated according to current guidelines and recommendations. PMID- 22051769 TI - [Melanotan]. PMID- 22051770 TI - The influence of ethanol containing cosmetics on ethyl glucuronide concentration in hair. AB - Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE), non-volatile, direct metabolites of ethanol have been shown to be suitable markers for the evaluation of social and chronic excessive alcohol consumption. Previous investigations have shown that the regular use of hair-care products with high alcohol content lead to an increase of FAEE concentration and consequently gave false-positive results for the determination of FAEE in hair. In this study we investigated the influence of a long-term hair treatment with EtOH containing lotion, on the EtG concentrations in hair. In this study 7 volunteer subjects (classified as either rare, social or heavy drinkers) treated the right side of their scalp every day during a one or two month period with a commercial hair tonic (Seborin), which contains 44.0% ethanol (vol%). Collection of hair specimens from both sides of the scalp was done one day before hair treatment, one week and one month after treatment (for 5 subjects also after two months of treatment). A hair segment of 3 centimeters (cm) was cut and then washed with water and acetone, and then pulverized. EtG was quantified by GC/MS after pulverization and 2h of ultrasonication in water, extraction by solid phase extraction using Oasis MAX columns and derivatization with HFBA. Measurements were done in negative chemical ionization mode using EtG-D5 as internal standard. Comparison of EtG concentration in the treated and in the non-treated hair specimens did not show any increase at the different dates of collection for the 7 subjects. In conclusion, these results show that there is no indication for an increase of EtG after use of ethanol containing hair cosmetics. PMID- 22051771 TI - Racial and ethnic disparities in access to and quality of health care. AB - Racial and ethnic disparities in access to care and quality of care are pervasive but not universal. This Synthesis reviews the evidence on racial and ethnic disparities. Key findings include: disparities exist in many indicators of access, such as having a usual source of care, number of ambulatory visits, and receiving recommended preventive care, but some disparities are reduced or nearly eliminated after adjusting for factors such as income and insurance coverage. Hispanics have a large gap relative to Whites in many access factors. Spanish speaking Hispanics have the greatest disparities relative to non-Hispanic whites, suggesting language is a barrier. Both Blacks and Hispanics are less likely than Whites to identify a doctor's office as their usual source of care, which can point to problems with continuity of care and less favorable outcomes. The most significant disparities in quality of care involve newer therapies and invasive procedures. Adjusting the data for insurance coverage demonstrates that expanding coverage will reduce but not eliminate disparities. PMID- 22051772 TI - Design of a magnesium-pridinolum complex for polylactide-drug conjugates formation. AB - Polylactide conjugates of the muscle contraction agent Pridinolum (PriOH = 1,1 diphenyl-3-(1-piperidinyl)-1-propanol) were prepared directly by ring-opening polymerization of L-lactide (L-LA) mediated by the pridinolum magnesium complex [Mg(MU,eta(2)-OPri)(eta(1)-OPri)](2). The ancillary O,N - bifunctional drug as a ligand stabilizes the magnesium species and initiates L-LA polymerization affording a polymer chain terminated by covalently attached drug molecules to the PLLA through ester linkers to form PriO-PLLA conjugate. Up to 80% of the pridinolum can be released from the conjugate by treatment with deuterated hydrochloric acid DCl at pH = 1.5 for 10 h at 37 degrees C. PMID- 22051773 TI - Expression of aquaporin-4 augments cytotoxic brain edema after traumatic brain injury during acute ethanol exposure. AB - We previously reported that ethanol consumption affects morbidity and mortality after traumatic brain injury (TBI) by accelerating brain edema via oxidative stress after TBI. Aquaporin-4 (AQP4), a water channel, is involved in brain edema formation. In this study, we found that acute ethanol administration increased AQP4 expression after TBI, leading to severe brain edema in rats. Rats were pretreated with ethanol (3 g/kg) or dl-buthionine-(S,R)-sulfoximine (BSO; 100 mg/kg), an oxidative stressor, before TBI. Acetazolamide, an AQP4 inhibitor, was administered to ethanol-pretreated rats 3 or 12 hours after TBI. Brain edema was increased 24 hours after TBI in both the ethanol- and BSO-pretreated groups. Ethanol pretreatment induced lipid peroxidation 24 hours after TBI. Transcription factors, NF-kappaB and hypoxia-inducible factor-1alpha, were activated 3 and 24 hours after TBI in the BSO- and ethanol-pretreated groups, respectively. In the ethanol-pretreated group, AQP4 was accumulated, particularly in astrocyte end feet, 24 hours after TBI. Acetazolamide treatment improved the survival rate to 100% and decreased brain edema and AQP4 in ethanol-pretreated rats. These findings suggest that ethanol induces up-regulation of AQP4, leading to brain edema. The accumulation of AQP4 may play an important role in the augmentation of brain edema after TBI under ethanol consumption. PMID- 22051774 TI - Chronic inflammatory cardiomyopathy of interferon gamma-overexpressing transgenic mice is mediated by tumor necrosis factor-alpha. AB - We recently described a model of inflammatory cardiomyopathy in interferon (IFN) gamma overexpressing transgenic mice stably circulating IFN-gamma in the serum referred to as SAP--IFN-gamma mice. SAP-IFN-gamma transgenic mice show cardiac infiltration by mononuclear leukocytes, culminating in dilated cardiomyopathy characterized by an increase of left ventricular end diastolic diameter and reduction of fractional shortening. We hypothesized that the pathological mechanism underlying SAP-IFN-gamma cardiomyopathy might be mediated by (auto)immune processes or tumor necrosis factor (TNF)-alpha synthesis from IFN gamma-activated macrophages. To verify these hypotheses, we crossed SAP-IFN-gamma transgenic mice with immunodeficient Rag1(-/-) or TNF-alpha(-/-) knockout mice and analyzed the cardiac phenotype of the resulting double-mutant offspring. Immunodeficient Rag1(-/-) SAP-IFN-gamma mice had a decreased impaired life span and intensive cardiac inflammatory reactions, showing that the cardiotoxic IFN gamma effect operative in SAP-IFN-gamma mice was not mediated by an adaptive immune mechanism. SAP-IFN-gamma TNF-alpha(-/-) hearts showed virtually no histopathological alterations, a significant reduction of cardiac infiltration by CD11c(+) dendritic cells and F4/80(+) macrophages, almost complete normalization of cardiac troponin T levels in serum and of left ventricular end diastolic diameter and fractional shortening, and a dramatic increase of life span, compared with SAP-IFN-gamma transgenic controls. Thus, myocarditis and cardiomyopathy developing in IFN-gamma-overexpressing transgenic mice is, to a significant degree, mediated by TNF-alpha. TNF-alpha-mediated cardiotoxicity in SAP-IFN-gamma transgenic mice is independent of changes of apoptosis. PMID- 22051775 TI - Heat shock proteins 27 and 70 are potential biliary markers for the detection of cholangiocarcinoma. AB - Cholangiocarcinoma often is diagnosed at an advanced stage. Thus, it is necessary to establish sensitive screening methods that would allow cholangiocarcinoma and preferably its precursor lesion [biliary intraepithelial neoplasia (BilIN)] to be detected. We sought to clarify the usefulness of heat shock protein (HSP) 27 and HSP70 as biomarkers of cholangiocarcinoma and have used immunohistochemical analyses of hepatolithiatic livers to characterize HSP27 and HSP70 expression during the multistep cholangiocarcinogenesis process. HSP27 and HSP70 were measured in serum and bile samples via enzyme-linked immunosorbent assay. In hepatolithiatic tissue, the expression of HSP27 and HSP70 was increased in BilIN as well as in invasive cholangiocarcinoma. The serum levels of HSP27 and HSP70 were not significantly different between the hepatolithiatic patients with and without cholangiocarcinoma. In contrast, the bile levels of HSP27 and HSP70 were increased significantly in the patients with cholangiocarcinoma compared with those in the patients with lithiasis. Combining the measurements of the bile levels of HSP27 and HSP70 increased their usefulness as biomarkers, and the sum (HSP27 + HSP70) yielded the best sensitivity (90%) and specificity (100%). These results suggest that HSP27 and HSP70 could be used as biliary biomarkers for the detection of cholangiocarcinoma including BilIN. PMID- 22051776 TI - Regulation of lipin1 by nutritional status, adiponectin, sex and pituitary function in rat white adipose tissue. AB - Lipin1 is a member of the lipin protein family that plays an important role in the regulation of lipid metabolism. The endogenous role of lipin1 was demonstrated by the fact that mutations in lipin1 caused lipodystrophy and metabolic disorders. The aim of this study was to assess the influence of nutritional status, pregnancy, insulin-sensitizers and pituitary hormones on lipin1 mRNA levels in adipose tissue of rats. Lipin1 gene expression was induced in conditions of hypoleptinemia (fasting) and leptin resistance (high fat diet), whereas it was decreased by high circulating leptin levels (leptin administration, pregnancy) and in leptin-deficient mice. Lipin1 mRNA levels were also decreased in adiponectin-deficient mice. Lipin1 mRNA levels are influenced by age in female rats, with peak expression at 25th day of life and decreasing thereafter. Consistently, ovariectomy increased lipin1 expression indicating that estrogens modulate lipin1. Finally, lipin1 was also regulated by pituitary hormones, since its expression was modified by thyroid status and growth hormone deficiency. Our observations indicate that: a) gWAT lipin1 mRNA levels are regulated by nutritional status, and leptin plays an important role in this regard, b) lipin1 is modulated by adiponectin, c) lipin1 is influenced by age and sex, and d) alterations in pituitary function modify lipin1 mRNA levels. To dissect the complicated interactions between key regulators of lipid metabolism like lipin1, may be important for the development of new therapies for the treatment and prevention of obesity and its associated disorders. PMID- 22051777 TI - Characterization of cis-regulatory elements controlling repo transcription in Drosophila melanogaster. AB - The glial cells missing (gcm) gene has been identified as a "master regulator" of glial cell fate in the fruit fly Drosophila. However, gcm is also expressed in and required for the development of larval macrophages and tendon cells. Thus, the Gcm protein activates the transcription of different sets of genes in different developmental contexts. How the Gcm protein regulates these different outcomes is not known. Our goal is to identify proteins that collaborate with Gcm to promote the transcriptional activation of Gcm target genes specifically in glial cells, or prevent their activation in the other tissues in which Gcm is expressed. To address this, we have focused on the transcriptional regulation of a well-characterized glial-specific Gcm target gene, the transcription factor reversed polarity (repo). We aim to understand how the transcription of the glial specific Gcm target gene repo is regulated by Gcm and other factors. Previously we defined a 4.3 kb cis-regulatory DNA region that recapitulates the endogenous Repo expression pattern dependent on multiple Gcm binding sites. We proposed that there may be multiple cis-regulatory sub-regions that drive cell-specific expression independent of Gcm binding sites. Here, using lacZ reporter activity in transgenic lines, we have characterized three cis-regulatory elements: 1) a distal element that promotes expression in dorsolateral epidermis; 2) a repressor element that suppresses expression in the epidermis; and, 3) a proximal element that promotes expression in a subset of cell body glia. Most significantly, we have defined a minimal cis-regulatory element that recapitulates the endogenous repo expression pattern dependent on a single Gcm binding site. PMID- 22051778 TI - 1kbp 5' upstream sequence enables developmental stage-specific expressions of globin genes in the fish, medaka Oryzias latipes. AB - Hemoglobin of bony fish and higher vertebrates is a tetrameric protein constructed by 2 alpha- and 2 beta-globins, which are expressed in a developmental stage-specific manner. The genomic organization of genes for embryonic and adult alpha- and beta-globin varies from species to species. In fish, it is known that there is a unique genomic organization of globin genes, that is, alpha- and beta-globin genes are arranged in a bi-directional and head to-head orientation with respect to transcription start sites. In medaka, we have demonstrated that 14 globin genes are located in 2 different clusters, and 5 pairs of the alpha- and beta-globin genes were found to be organized in a head-to head orientation. The developmental expression patterns of the 11 globin genes were classified into 4 types. To clarify how their developmental stage-specific expressions are regulated, we produced 4 types of GFP- or RFP-transgenic medaka. Such transgenic medaka revealed that each of the 1-1.7 kbp 5' upstream sequences from respective globin genes possesses the ability to regulate the developmental stage-specific globin gene expression. In particular, the intervals between head to-head alpha3 and beta3, and alpha4 and beta4 genes controlled the synchronized expression of the globin genes located at both sides of the intervals, which is significant to understand the mechanism by which equal amounts of alpha- and beta globins are expressed in erythroid cells. We also demonstrated that the head-to head intervals can control the expression of the globin genes located at both sides. These findings are significant to understand the mechanism by which alpha- and beta-globins are equally expressed in erythroid cells. PMID- 22051779 TI - Citation analysis of the contact lens field. AB - PURPOSE: To identify, analyze, and celebrate the most highly cited articles relating to contact lenses and the leading authors, journals, institutions, and countries associated with these publications. METHODS: To capture all contact lens articles published since 1900, a search equation targeting specific contact lens-related terms in the titles of articles was derived and entered into "Web of Science." A rank order list of the 1000 most highly cited articles was assembled, each having received at least eight citations. The most prominent articles, authors, journals, institutions, and countries were identified from this list by simple counts. RESULTS: The most highly cited article relating to contact lenses (although cited exclusively in the physical sciences literature) is that of Phillip and Schmidt (J Non Cryst Solids 1984;63:288-92), reporting the application of the sol-gel process for the fabrication of rigid contact lenses. Eight of the top 10 articles ranked according to average number of citations/year relate to contact lens-associated microbial keratitis. Of the top eight authors, six have spent all, or a substantial proportion, of their academic careers in Australia and seven have worked in optometric research environments. Optometry and Vision Science is the leading journal. The top-ranked institution is The University of New South Wales, Sydney, Australia. The United States is the most prominent publishing country in the field, and Australia ranks highest when the numbers of highly cited articles are considered per head of population. CONCLUSIONS: This work provides a unique snapshot of significant articles relating to contact lenses. PMID- 22051780 TI - Asthenopia and blink rate under visual and cognitive loads. AB - PURPOSE: Asthenopia has been associated with reading under visually stressful conditions. However, it is not known whether increased cognitive load contributes to asthenopic symptoms. The purpose of this study was to evaluate the contribution of increased cognitive load (with or without visual stress inducing conditions) to asthenopic symptoms associated with prolonged near work. METHODS: Thirty-three visually normal subjects, aged 18 to 30 years, participated in the study. Subjects read texts or watched videos under different visual stress and cognitive loads. Visual stress conditions were good visual quality, low contrast, and induced refractive error. The cognitive load levels were watching video, reading fairy tales, and reading technical articles. As an additional task, subjects also listened to technical articles. At the end of each condition, subjects rated the magnitude of any asthenopic symptoms, visual discomfort, and cognitive discomfort they experienced during the task. Electromyography potentials recorded from the lower orbicularis oculi muscle were used to obtain blink rate. RESULTS: Subjects reported greater internal symptoms for the refractive error condition coupled with higher cognitive load compared to good visual and low contrast conditions (p < 0.01). For the low contrast condition coupled with higher cognitive load, greater external symptoms were reported compared to good visual and refractive error conditions (p < 0.05). However, asthenopic symptoms were not reported for cognitively demanding tasks when the visual condition was good. Blink rates were not significantly different between the good visual and low contrast conditions within each cognitive load level. For the cognitively difficult reading conditions, blink rate was significantly decreased for the low contrast and good visual conditions compared to the refractive error condition. CONCLUSIONS: An interaction between cognitive and visual demands was observed. Greater cognitive loads accentuate the same differentiated symptoms normally caused by visual stressors. PMID- 22051781 TI - Two cases of keratoconus diagnosed after pregnancy. AB - PURPOSE: This case report aims to demonstrate that pregnancy-induced biomechanical corneal changes in combination with risk factors for ectasia can develop into (the exacerbation of) keratoconus. CASE REPORT: We describe two women who were clinically diagnosed with keratoconus after their second pregnancy. Both women were myopic and had a history of allergies and contact lens wear. It is unclear whether these two women had a newly diagnosed keratoconus that developed during pregnancy or had experienced an exacerbation of an unrecognized, subclinical keratoconus. CONCLUSIONS: Nowadays, documented progression of keratoconus can be treated by corneal crosslinking to stabilize the weakened cornea. Therefore, it is important to understand the effects of hormonal changes in (keratoconic) eyes during pregnancy and to include topographic imaging in unexplained visual deterioration in young individuals, especially during or after a pregnancy. PMID- 22051782 TI - Heterologous production of bisucaberin using a biosynthetic gene cluster cloned from a deep sea metagenome. AB - A siderophore biosynthetic gene cluster was cloned from a metagenomic library generated from deep sea sediment. The gene cluster was successfully expressed in Escherichia coli to produce bisucaberin, a siderophore originally reported from the marine bacterium Alteromonas haloplanktis. The cloned bisucaberin biosynthetic gene cluster was moderately similar to that of the known bisucaberin producer Vibrio salmonicida. However, the cloned gene cluster consists of four genes rather than three genes found in the V. salmonicida cluster. The low overall homology of the amino acid and nucleotide sequences with those of other species suggests that the cloned genes were derived from one of the unsequenced bacteria including uncultured species. PMID- 22051783 TI - Ovarian endometrioma in an 11-year-old girl before menarche: a case study with literature review. AB - BACKGROUND: To date, a limited number of endometriosis cases occurring before or around the time of menarche have been documented. CASE: An 11-year-old adolescent underwent an emergency operation for left ovarian endometrioma. Her menarche occurred spontaneously 6 months after surgery. RESULTS AND CONCLUSIONS: We discuss the above mentioned case and consider data published in the literature. Endometrioma should be considered even in premenarcheal girls with ovarian cysts, regardless of their size. PMID- 22051784 TI - The use of effective contraception among young Hispanic women: the role of acculturation. AB - PURPOSE: Culture may play an important role in contraceptive preference among young Hispanic women. We examined whether acculturation predicted the use of different contraceptives, grouped by level of efficacy in preventing pregnancy. METHODS: 1017 sexually active Hispanic women between the ages of 16 and 24 (mean age 20.69 +/- 2.42 years) responded to a self-administered questionnaire. Data were analyzed using multinomial logistic regression. RESULTS: Women low in acculturation (OR 1.79, CI 1.06-3.02) and bicultural (OR 2.66, CI 1.52-4.64) were more likely than women high in acculturation to have used no method of contraception than long-acting reversible contraception (LARC). Bicultural women were more likely to have used condoms than LARC (OR 2.51, CI 1.40-4.49) compared to women high in acculturation. Finally, women in low in acculturation (OR 1.98, CI 1.11-3.50) and bicultural (OR 1.88, CI 1.01-3.51) were more likely to have used cyclic hormonal contraception than LARC compared to women high in acculturation. CONCLUSIONS: Educational efforts should focus on young Hispanic women who are bicultural and low in acculturation in order to increase their use of more effective contraceptive methods and reduce the number of unplanned pregnancies among this population. PMID- 22051785 TI - Cultural practices relating to menarche and menstruation among adolescent girls in Taiwan--qualitative investigation. AB - STUDY OBJECTIVE: The aim of this study was to qualitatively record the cultural attitudes and practices associated with menarche and menstruation in Taiwanese girls, particularly with respect to coping mechanisms. PARTICIPANTS: Forty-eight adolescent girls participated. INTERVENTION: Adolescent girls were individually interviewed to investigate the effects of their cultural practices, coping mechanisms, and physiological symptoms during menarche and menstruation. MAIN OUTCOME MEASURE(S): The qualitative investigation revealed mixed reactions to menstruation, such as eating chocolate, using sanitary napkins, and feeling irritable or embarrassed. Cluster construction suggested that adolescents were prepared for menarche but required emotional support; in addition, the new generation employed the Internet to learn how to cope. RESULTS: A phenomenological approach showed that menarche and menstrual attitudes among Taiwanese adolescents were comprised in 4 dimensions: self-perception, information, and cultural practices with regard to menarche; physiological symptoms and psychological reactions during menstruation; coping mechanisms during menarche and menstruation; and methods for coping and cultural practices for menstruation. Cultural beliefs and the Internet have changed cross-cultural contacts. CONCLUSIONS: Educators and health professionals should seek to understand this generation of girls, who perceive the world as more flexible and available and have more creativity and new eating behaviors and hobbies. PMID- 22051786 TI - Vaginal agenesis, the hymen, and associated anomalies. AB - STUDY OBJECTIVES: Review anomalies in patients with vaginal agenesis. In particular, to clarify the impact of an absent hymen on the presence of other anomalies; on the success of creating a vagina with dilators; and on sexual function outcomes. DESIGN: Retrospective medical record review; questionnaire on sexual function. SETTING: Gynecology service at a children's hospital and the practice of 1 gynecologist. PARTICIPANTS: All patients with vaginal agenesis were identified from the databases, as well as the subgroup in which hymenal status was known. OUTCOME MEASURES: Data regarding hymen, renal, skeletal, cardiac, and other anomalies; for women who had a neovagina, the technique used to create a functional vagina. RESULTS: Of 69 females (age range 2-70 years), renal tract anomalies (43.3%), vertebral anomalies (29%), cardiac anomalies (14.5%), and syndromes including Klippel-Feil (7%) and MURCS association (7%) were identified. Where hymenal status was known (n = 47), 31 were normal, and 16 had an absent hymen. Where the hymen was absent, renal agenesis was increased (odds ratio = 13.5, P < .001). There was no association between other anomalies and an absent hymen, or between the various anomalies. For women without a hymen, the likelihood of failing dilation therapy was increased (odds ratio = 21.7; P < .01]. CONCLUSION: An absent hymen makes renal agenesis more likely and increases the likelihood that dilator techniques will fail. This condition appears to be associated with reports of long-term problems with poor lubrication that are potentially related to the absence of the peri-hymenal Bartholin's glands. PMID- 22051787 TI - Urogenital symptoms in premenarchal girls: parents' and girls' perceptions and associations with irritants. AB - OBJECTIVES: Premenarchal girls commonly seek care for urogenital symptoms, yet little is published about parents' and girls' perceived causes of symptoms or associations with irritant exposures. We sought to describe urogenital symptoms, perceived causes, and associations between symptoms and genital irritant exposures. DESIGN: Descriptive study. Parents/girls interviewed; medical records reviewed. PARTICIPANTS: Five- to 12-year-old well, premenarchal girls and their parents. SETTING: One urban and 1 suburban pediatric practice. OUTCOME MEASURES: Prevalence of histories of urogenital symptoms and perceived causes; association between symptoms and exposure to genital irritants in a well population. RESULTS: Of 191 parent/girl dyads, 33% of parents and 48% of girls reported girls' histories of urogenital symptoms not attributed to urinary tract infections or trauma. Perceived causes: poor hygiene (29% of parents vs 14% of girls); soap products (20% of parents and girls); none identified (24% of parents vs 53% of girls). Analysis of symptoms versus irritant exposures demonstrated these associations: dysuria and genital soreness with poor genital hygiene, tight garments, or exposure to soap products; genital pruritus with poor hygiene (all P < .05). No symptoms were associated with nylon underwear, tights, or bike or horseback riding. Vaginal discharge was not associated with any irritants. CONCLUSION: Almost half the girls had histories of urogenital symptoms. Poor hygiene and soap exposure were perceived causes of most symptoms. When no cause for urogenital symptoms is identified, treatment should be focused on hygiene, soap exposure, and tight-fitting clothes, not on bike or horseback riding or wearing nylon underwear or tights. Vaginal discharge warrants further evaluation. PMID- 22051788 TI - Substance use and mental health disparities among sexual minority girls: results from the Pittsburgh girls study. AB - PURPOSE: To examine substance use and mental health disparities between sexual minority girls and heterosexual girls. METHODS: Data from the Pittsburgh Girls Study were analyzed. All girls were 17 years old. Girls were included if they were not missing self-reported sexual orientation and mental health data (N = 527). Thirty-one girls (6%) endorsed same-sex romantic orientation/identity or current same-sex attraction. Bivariate analyses were conducted to test group differences in the prevalence of substance use and suicidal behavior, and group differences in depression, anxiety, borderline personality disorder (BPD), oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms. RESULTS: Compared with heterosexual girls, sexual minority girls reported higher past-year rates of cigarette, alcohol, and heavy alcohol use, higher rates of suicidal ideation and self-harm, and higher average depression, anxiety, BPD, ODD, and CD symptoms. CONCLUSIONS: Sexual minority girls are an underrepresented group in the health disparities literature, and compared with heterosexual girls, they are at higher risk for mental health problems, most likely because of minority stress experiences such as discrimination and victimization. The disparities found in this report highlight the importance of discussing sexual orientation as part of a comprehensive preventive care visit. PMID- 22051789 TI - Diagnosis and management of precocious puberty in atypical presentations of McCune-Albright syndrome: a case series review. AB - BACKGROUND: McCune-Albright syndrome is a rare syndrome, classically defined as the triad of precocious puberty, fibrous dysplasia of bone, and cafe au lait lesions. Partial or atypical presentations of McCune-Albright syndrome, with only one or two of the classic symptoms, have been described in the literature and remain particularly challenging due to lack of diagnostic phenotype. In these patients, the utility of analysis of mutations in the gene of the alpha subunit of the stimulatory G-protein is limited and so the diagnosis is often based on clinical judgment. Three atypical cases of suspected McCune-Albright syndrome with gonadotropin-independent precocious puberty are presented. CASES: Case #1: A 5-year-old female presented with painlesss vaginal bleeding and was found to have cafe au lait lesions. She was diagnosed with gonadotropin independent precocious puberty with eventual progression to gonadotropin dependent precocious puberty which was successfully treated with both letrozole and gonadotropin-releasing hormone agonist therapy. Case #2: A 3-year-old female presented with painless vaginal bleeding and was found to have cafe au lait lesions. She was diagnosed with gonadotropin independent precocious puberty and was successfully treated with letrozole. Case #3: A 5-year-old female presented with fibrous dysplasia and was found to have evidence of uterine and ovarian enlargement on ultrasound. She was diagnosed with gonadotropin-independent precocious puberty and was successfully treated with letrozole. SUMMARY AND CONCLUSION: Although different in presentation, all three atypical cases of suspected McCune-Albright syndrome with gonadotropin-independent precocious puberty were successfully treated with aromatase inhibitors. This small case series shows the utility and efficacy of aromatase inhibitors in the setting of atypical cases of suspected MAS with gonadotropin-independent precocious puberty. PMID- 22051791 TI - Awareness and knowledge of the intrauterine device in adolescents. AB - BACKGROUND: The purpose of this study was to explore intrauterine device (IUD) awareness and knowledge in a diverse, multiethnic population. METHODS: We conducted a self-administered, anonymous survey addressing awareness of the IUD as a contraceptive method and knowledge about aspects of IUD use in a group of women aged 14 to 19 years. Demographic and medical information was obtained to compare awareness and knowledge between demographic groups. Chi-square, Fisher exact test, and t tests were used for analysis. Multiple logistic regression was utilized to confirm relationships. RESULTS: Of the 106 respondents, 76.4% (81/106) were sexually active and 56.6% (60/106) reported a history of ever being pregnant. There were 21.1% (33/106) of respondents who had heard of the IUD as a contraceptive method. Of the subjects who had heard of the IUD, 39.4 % (13/33) were able to identify key features of the IUD. Although a history of pregnancy was predictive of having heard of the IUD, age, insurance status, education, and all other demographic factors were not associated with IUD awareness. CONCLUSION: Over 70% of the adolescents had not heard of the IUD and less than half of adolescents who had heard of the IUD were able to identify key features about this contraceptive method. The lack of knowledge of this effective and safe contraceptive option is concerning given that most participants were at high risk for unintended pregnancy. PMID- 22051790 TI - Prevalence and correlates of recent vaginal douching among African American adolescent females. AB - STUDY OBJECTIVE: To describe the prevalence and correlates of vaginal douching among urban African American adolescents and to examine the association between douching and sexually transmitted infection (STI) status. DESIGN: Demographic, psychosocial, and behavioral data were collected through cross-sectional, self administered surveys. Self-collected vaginal swabs were assayed using nucleic acid amplification tests for trichomoniasis, chlamydia, and gonorrhea. SETTING: Sexual health clinic in a large metropolitan area of the southeastern United States. PARTICIPANTS: African American females (N = 701), ages 14-20, participating in a human immunodeficiency virus prevention intervention. MAIN OUTCOME MEASURE: The outcome of interest was the association between vaginal douching (lifetime, past 90 days, and past 7 days) with demographic characteristics (eg, age, education, and socioeconomic status), physical and mental health status, STI status, sexual behavior (eg, number of vaginal sexual partners, age of sex partners, consistent condom use in the past 90 days, sex while self/partner was high on drugs or alcohol), and psychosocial characteristics (eg, sexual adventurism, social support, peer norms, sexual satisfaction, self-efficacy for sex refusal, self-esteem, relationship power, risk avoidance). RESULTS: Forty-three percent reported ever douching, and 29% reported douching in the past 90 days. In bivariate analyses, recent douching was associated with demographic, behavioral, and psychosocial variables, but not current STI status. In multivariate analyses, recent douching was associated with age (odds ratio [AOR] = 1.13, confidence interval [CI] = 1.02-1.25), lower socioeconomic status (AOR = 1.25, CI = 1.05-1.47), and having sex with much older partners (AOR = 1.87, CI = 1.22-2.86). CONCLUSION: Increased age, lower socioeconomic status, and older partners may be salient risk factors for douching behavior among African American young women. PMID- 22051792 TI - Long acting reversible contraception in postpartum adolescents: early initiation of etonogestrel implant is superior to IUDs in the outpatient setting. AB - STUDY OBJECTIVE: To evaluate the outpatient initiation of postpartum long-acting reversible contraception (LARC). DESIGN: Prospective cohort study of pregnant adolescents' prenatal contraceptive intentions and successful postpartum initiation of LARC. SETTING: Urban, university hospital-affiliated, adolescent outpatient clinic. PARTICIPANTS: Adolescents attending an integrated prenatal and postpartum maternity clinic. INTERVENTIONS: Data were collected via the electronic medical record and telephone interview. MAIN OUTCOME MEASURES: Contraceptive intentions during the third trimester, contraceptive methods used postpartum, timing of LARC initiation, timing of resumption of intercourse. RESULTS: 116 patients were enrolled; 75% intended LARC use postpartum. Of 38 implant-intenders, 14 received it within 14 days postpartum. All reported abstinence pre-placement. Mean time to insertion was 18+/-13 days. Of 37 IUD intenders, only two received one by 8 weeks postpartum. By 14 weeks postpartum, 43% received one. Over half reported intercourse prior to insertion; the only method of contraception used was condoms. Mean time to insertion was 70+/-11 days. Resumption of intercourse prior to initiation of the intended LARC method was significantly higher in IUD recipients compared to those who intended and received the implant (RR 8.8; CI 1.3-57.5). CONCLUSION: In postpartum teens attending a clinic that prioritizes contraceptive use, the implant is far more likely to be received prior to resumption of sexual activity than the IUD. This may be due to more and earlier opportunities for placement, or waning commitment with time since delivery. Post-placental IUDs may be needed to equal the success of the implant in this patient population. Short-acting, reliable contraceptive methods should be implemented for postpartum adolescents preferring to wait for IUD insertion. PMID- 22051793 TI - The role of examination under anesthesia (EUA) and vaginoscopy in pediatric and adolescent gynecology: a retrospective review. AB - BACKGROUND: Examination under anesthesia (EUA) with diagnostic vaginoscopy is an invaluable method in the lower genital tract assessment of pediatric and adolescent females. The literature on this topic remains scarce. METHODS: This is a retrospective medical notes review of all patients who underwent EUA with or without vaginoscopy over the past 5 years at a pediatric and adolescent gynecology unit specializing in disorders of sex development (DSD). RESULTS: From 2005 to 2010, 83 patients underwent 92 procedures. All procedures were performed under general anesthesia, and a 3-mm pediatric cystoscope was used for vaginoscopy. Of the 92 cases, 33 (36%) were EUA alone and 59 (64%) consisted of a combined EUA and vaginoscopy. The mean age was 13.3 +/- 3.7 years. The most common indications included assessment for reconstructive surgery (33.7%), vaginal stenosis (21.7%), vaginal discharge (19.6%), vaginal bleeding (16.3%), and pelvic pain (8.7%). Most (61%) of those presenting for assessment for reconstructive surgery had a DSD and history of surgical correction in early childhood. In 88 cases (96%), the evaluation was satisfactory and a diagnosis was reached or normality confirmed. Four cases (4%) required further investigation. No significant intraoperative or postoperative complications were encountered. Of the 92 cases, 15 (16%) required a further minor procedure, which was performed at the time of the EUA/vaginoscopy. Another 33 (36%) required further major surgery, which was performed at a later date. CONCLUSION: EUA/vaginoscopy is a safe and highly useful method in the assessment of the lower genital tract in pediatric and adolescent patients. PMID- 22051794 TI - The rechargeable aluminum-ion battery. AB - We report a novel aluminium-ion rechargeable battery comprised of an electrolyte containing AlCl(3) in the ionic liquid, 1-ethyl-3-methylimidazolium chloride, and a V(2)O(5) nano-wire cathode against an aluminium metal anode. The battery delivered a discharge capacity of 305 mAh g(-1) in the first cycle and 273 mAh g( 1) after 20 cycles, with very stable electrochemical behaviour. PMID- 22051795 TI - Widespread polymorphism in the positions of stop codons in Drosophila melanogaster. AB - The mechanisms underlying evolutionary changes in protein length are poorly understood. Protein domains are lost and gained between species and must have arisen first as within-species polymorphisms. Here, we use Drosophila melanogaster population genomic data combined with between species divergence information to understand the evolutionary forces that generate and maintain polymorphisms causing changes in protein length in D. melanogaster. Specifically, we looked for protein length variations resulting from premature termination codons (PTCs) and stop codon losses (SCLs). We discovered that 438 genes contained polymorphisms resulting in truncation of the translated region (PTCs) and 119 genes contained polymorphisms predicted to lengthen the translated region (SCLs). Stop codon polymorphisms (SCPs) (especially PTCs) appear to be more deleterious than other polymorphisms, including protein amino acid changes. Genes harboring SCPs are in general less selectively constrained, more narrowly expressed, and enriched for dispensable biological functions. However, we also observed exceptional cases such as genes that have multiple independent SCPs, alleles that are shared between D. melanogaster and Drosophila simulans, and high frequency alleles that cause extreme changes in gene length. SCPs likely have an important role in the evolution of these genes. PMID- 22051796 TI - An enhanced MODIS remote sensing model for detecting rainfall effects on sediment plume in the coastal waters of Apalachicola Bay. AB - Mapping of total suspended solids (TSS) was conducted to investigate rainstorm induced characteristic of sediment plume in the coastal waters of Apalachicola Bay. An improved TSS quadratic polynomial regression model (Calibration: R2=0.8586, N=32; validation: RMSE of 4.76 mg/l, N=30) for MODIS remote sensing was presented in this study. TSS mapping of MODIS before and after a rainstorm event showed distinct temporal-spatial variability of TSS concentration. Driven by ocean tidal current, a storm plume of width at about 40-50 km was formed flowing towards southwest of study area. The distinct boundary separating the highly turbid (west side) and relatively clear water (east side) was found near Sikes Cut. Further, by taking the TSS mapping under the low river discharge condition due to a local rainstorm as a reference of background TSS, two thresholds of TSS (25 and 45 mg/l respectively) were used to estimate the range of rainstorm plume and the central area of sediment load from surrounding land, and the spatial extent and evolution of the sediment plume during the local rainstorm. Besides, it was found that the storm plume concentration of TSS at east side of Sites Cut was quickly diluted under 25 mg/L, forming a storm plume towards east with width at about 7-8 km. The method developed in this study may be used to support coastal storm water research and management activities. PMID- 22051797 TI - Imaging protein activity in live embryos using fluorescence resonance energy transfer biosensors. AB - Fluorescence resonance energy transfer (FRET)-based molecular biosensors serve as important tools for studying protein activity in live cells and have been widely used for this purpose over the past decade. However, FRET biosensors are rarely used in the context of the live organism because of the inherent high cellular complexity and imaging challenges associated with the three-dimensional environment. Here we provide a protocol for using single-chain intramolecular FRET-based biosensors in early development. We provide a general protocol for FRET ratio imaging in embryos, including the data-acquisition conditions and the algorithm for ratio image generation. We then use the pRaichu RacFRET biosensor to exemplify the adaptation and optimization of a particular biosensor for use in live zebrafish embryos. Once an optimized biosensor is available, the complete procedure, including introduction of the probes into embryos, imaging and data analysis, requires 2-3 d. PMID- 22051798 TI - Using an adherent cell culture of the mouse subependymal zone to study the behavior of adult neural stem cells on a single-cell level. AB - A comprehensive understanding of the cell biology of adult neural stem cells (aNSCs) requires direct observation of aNSC division and lineage progression in the absence of niche-dependent signals. Here we describe a culture preparation of the adult mouse subependymal zone (SEZ), which allows for continuous single-cell tracking of aNSC behavior. The protocol involves the isolation (approximately 3 h) and culture of cells from the adult SEZ at low density in the absence of mitogenic growth factors in chemically defined medium and subsequent live imaging using time-lapse video microscopy (5-7 d); these steps are followed by postimaging immunocytochemistry to identify progeny (approximately 7 h). This protocol enables the observation of the progression from slow-dividing aNSCs of radial/astroglial identity up to the neuroblast stage, involving asymmetric and symmetric cell divisions of distinct fast-dividing precursors. This culture provides an experimental system for studying instructive or permissive effects of signal molecules on aNSC modes of cell division and lineage progression. PMID- 22051799 TI - Transcription factor binding predictions using TRAP for the analysis of ChIP-seq data and regulatory SNPs. AB - The transcription factor affinity prediction (TRAP) method calculates the affinity of transcription factors for DNA sequences on the basis of a biophysical model. This method has proven to be useful for several applications, including for determining the putative target genes of a given factor. This protocol covers two other applications: (i) determining which transcription factors have the highest affinity in a set of sequences (illustrated with chromatin immunoprecipitation-sequencing (ChIP-seq) peaks), and (ii) finding which factor is the most affected by a regulatory single-nucleotide polymorphism. The protocol describes how to use the TRAP web tools to address these questions, and it also presents a way to run TRAP on random control sequences to better estimate the significance of the results. All of the tools are fully available online and do not need any additional installation. The complete protocol takes about 45 min, but each individual tool runs in a few minutes. PMID- 22051800 TI - Multiplexed array-based and in-solution genomic enrichment for flexible and cost effective targeted next-generation sequencing. AB - The unprecedented increase in the throughput of DNA sequencing driven by next generation technologies now allows efficient analysis of the complete protein coding regions of genomes (exomes) for multiple samples in a single sequencing run. However, sample preparation and targeted enrichment of multiple samples has become a rate-limiting and costly step in high-throughput genetic analysis. Here we present an efficient protocol for parallel library preparation and targeted enrichment of pooled multiplexed bar-coded samples. The procedure is compatible with microarray-based and solution-based capture approaches. The high flexibility of this method allows multiplexing of 3-5 samples for whole-exome experiments, 20 samples for targeted footprints of 5 Mb and 96 samples for targeted footprints of 0.4 Mb. From library preparation to post-enrichment amplification, including hybridization time, the protocol takes 5-6 d for array-based enrichment and 3-4 d for solution-based enrichment. Our method provides a cost-effective approach for a broad range of applications, including targeted resequencing of large sample collections (e.g., follow-up genome-wide association studies), and whole-exome or custom mini-genome sequencing projects. This protocol gives details for a single tube procedure, but scaling to a manual or automated 96-well plate format is possible and discussed. PMID- 22051802 TI - Levamisole-induced necrosis of skin, soft tissue, and bone: case report and review of literature. AB - This represents the largest case of skin necrosis related to levamisole, a common cocaine contaminant, requiring closure with skin grafts, and is the only case resulting in nasal amputation, central upper lip excision, extremity bone necrosis, and above knee amputation. The case report is followed by a review of the literature. Unique considerations for the full-thickness necrosis induced by levamisole vasculitis are highlighted, including antibody level monitoring, need for multiple excisions, timing of skin grafting, and potential for soft tissue and bone necrosis as well. A 54-year-old man presented to an outside facility with fever, generalized weakness, and agranulocytosis, with a history of cocaine use 3 weeks before. After admission, he developed generalized violaceous lesions and an elevated p-antineutrophilic cytoplasmic antibody and was diagnosed with disseminated vasculitis and agranulocytosis secondary to levamisole-contaminated cocaine exposure. On transfer to the authors' facility, 52% TBSA was involved with violaceous, nonblanching lesions, which progressed to full-thickness necrosis. Local wound care continued until necrotic areas fully demarcated and progressive necrosis stabilized, and skin grafting for closure was not performed until antibody levels normalized. Current treatment of levamisole-induced skin rash or necrosis focuses on discontinuation of levamisole. As demonstrated by this case, extensive necrosis secondary to levamisole-induced vasculitis can be successfully treated with multiple excisions until necrosis stabilizes, and then, split-thickness autografts may be applied. In areas with poor vascular supply or areas with poor functional prognosis, amputation may ultimately be required. PMID- 22051801 TI - Imaging of rat optic nerve axons in vivo. AB - In this protocol, we describe the imaging of single axons in the rat optic nerve in vivo. Axons are labeled through the intravitreal injection of adeno-associated viral vectors (AAVs) expressing a fluorophore (duration of the procedure ~1 h). Two weeks after intravitreal injection, the optic nerve is surgically exposed (duration ~1 h) and labeled axons are imaged with an epifluorescence microscope either for up to 8 h or repetitively on the following days. Additionally, intravitreal injection of calcium-sensitive dyes allows for imaging of intra axonal calcium kinetics. This procedure enables the analysis of the morphological changes of degenerating axons in the optic nerve in different lesion paradigms, such as optic nerve crush, axotomy or pin lesion. Furthermore, the effects of pharmacological manipulations on axonal stability and axonal calcium kinetics in axons of the central nervous system can be studied in vivo. PMID- 22051803 TI - [Cystic lesion in the area of the vestibular folds]. AB - Warthin tumor is the second most frequently seen benign tumor of the salivary glands and is generally located in the parotid gland. Although extraparotideal manifestations in the small salivary glands are rare, the occurrence of cystic lesions in the area of the nasopharynx, eyelid, oral cavity or vestibular folds should include the Warthin tumor in the differential diagnosis. The therapy of choice is complete surgical tumor resection. PMID- 22051804 TI - Expression pattern analysis of DNA repair-related and DNA damage response genes revealed by 55K oligomicroarray upon UV-B irradiation in the intertidal copepod, Tigriopus japonicus. AB - Ultraviolet-B (UV-B) radiation affects the genome stability of aquatic organisms by absorption of certain wavelength at the molecular level. Recently, extensive gene information has been identified from the intertidal copepod, Tigriopus japonicus. Here, we developed a 55K (54,254 genes) oligomicroarray and tested its usefulness to identify the effect of single dose of UV-B irradiation (12 kJ/m(2)) on transcriptomes of the copepod T. japonicus. A total of 35,361 spots were identified to be significantly modulated on the 55K oligomicroarray by hierarchical clustering after exposure to UV-B irradiation over 48 h (6, 12, 24, and 48 h). Of them, 1300 and 588 genes were observed to be up-regulated and down regulated at all time points, respectively. Particularly, it was observed that several genes involved in DNA repair mechanism were significantly modulated in the UV-B-exposed T. japonicus by microarray and quantitative real-time RT-PCR analysis. In detail, UV-B irradiation specifically up-regulated some genes in non homologous end-joining (NHEJ), homologous recombination (HR), base excision repair (BER), and mismatch repair (MMR) pathways. On the other hand, a majority of down-regulated genes were representatives for the nucleotide excision repair (NER) mechanism. These results demonstrated that DNA damage would be induced by UV-B irradiation in this species, resulting in reliable induction or repression of various DNA repair mechanism on UV-B-induced DNA damage. In this report, we suggest that a high density microarray-based approach for risk assessment of UV-B irradiation would be useful to elucidate the mechanistic analysis in a non-model organism. This study could also provide a better understanding of molecular mechanisms of cellular protection against UV-B-induced stress. PMID- 22051805 TI - Stenting from the vertebral artery to the posterior inferior cerebellar artery. AB - BACKGROUND AND PURPOSE: There are only a few reports on the feasibility and safety of stents used in the PICA, and clinical and angiographic follow-up results have not been fully addressed. We report our experiences of treating PICA origin or vertebral artery-PICA lesions by using self-expanding stents as adjuvant or rescue therapy with angiographic and clinical follow-up results. MATERIALS AND METHODS: Six patients were treated with self-expanding stent placements from the vertebral artery to the PICA. Two patients had a vertebral artery dissecting aneurysm involving the PICA origin, 3 had vertebral artery-PICA aneurysms, and 1 had segmental stenosis of the vertebral artery harboring the origin of the PICA. The safety, feasibility, and follow-up angiographic results were retrospectively evaluated. RESULTS: All procedures were successfully performed without any procedure-related complications. None of the patients showed PICA territorial infarction on DWI posttreatment. All patients were neurologically intact during the clinical follow-up of 3-24 months following the procedure. Follow-up angiography was performed at between 6 and 12 months in 5 of the 6 patients and was scheduled for the sixth patient but was not performed. The PICA showed good patency without in-stent stenosis in all 5 patients. CONCLUSIONS: In patients with lesions of the PICA origin or vertebral artery-PICA lesions, vertebral artery-to-PICA stent placement may be an option for preserving PICA patency in selected cases. PMID- 22051806 TI - Visualization of internal carotid artery atherosclerotic plaques in symptomatic and asymptomatic patients: a comparison of optical coherence tomography and intravascular ultrasound. AB - BACKGROUND AND PURPOSE: OCT has been reported as a high-resolution imaging tool for characterizing plaque in the coronary arteries. The present study aimed to evaluate the ability of OCT to visualize carotid artery plaques compared with that of IVUS in asymptomatic and symptomatic patients. MATERIALS AND METHODS: OCT was performed for 34 plaques (17 symptomatic, 17 asymptomatic) in 30 patients during CAS under a proximal cerebral protection method. OCT was performed before balloon angioplasty and after stent placement. IVUS was also performed just after OCT. RESULTS: No technical or neurologic complications were encountered by using OCT. An inner catheter was used in 12 of 34 procedures (35.3%) for advancing the OCT image wire beyond the site of stenosis. OCT clearly visualized intraluminal thrombus in 15 of 34 plaques (44.1%), whereas IVUS detected a thrombus in 1 plaque (2.9%, P < .001). Neovascularization was demonstrated in 13 of 34 plaques (38.2%) by OCT, but not by IVUS (0%, P < .001). Intraluminal thrombus was more frequently observed in symptomatic plaques (13 of 17, 76.5%) than in asymptomatic plaques (2 of 17, 11.8%; P < .001). Interobserver and intraobserver variability with OCT diagnosis was excellent for thrombus, ulceration, neovascularization, and lipid pool. CONCLUSIONS: The present findings suggest that OCT can safely and precisely visualize human carotid plaques during CAS and that intraluminal thrombus and neovascularization are more frequently detected in symptomatic plaques. PMID- 22051807 TI - Different iron-deposition patterns of multiple system atrophy with predominant parkinsonism and idiopathetic Parkinson diseases demonstrated by phase-corrected susceptibility-weighted imaging. AB - BACKGROUND AND PURPOSE: MSA-P and IPD have similar clinical presentations that may complicate accurate clinical diagnosis. Different iron-deposition patterns of those 2 diseases have been demonstrated in histopathology. The aim was to demonstrate the different iron-deposition patterns of MSA-P and IPD by using SWI phase images. MATERIALS AND METHODS: Sixteen patients with IPD, 8 with MSA-P, and 44 age-matched healthy controls underwent SWI of brain. The different phase shifts as well as the high iron percentage of the area in several gray nuclei were statistically evaluated. The putamen was divided into 4 subregions for further analysis. RESULTS: Patients with MSA-P had significantly higher iron deposition in the putamen and PT compared with those with IPD (P < .05). Moreover, ROC curves indicated slightly more sensitivity in differentiating MSA-P from IPD, by means of the high-iron-deposition-percentage area than the average phase shift (putamen: AUC = 0.88 versus 0.78; PT: AUC = 0.79 versus 0.62). Moreover, the lower inner region of the putamen was the most valuable subregion in differentiating MSA-P from IPD among the 4 subregions (AUC = 0.92 and 0.91 for high-iron-percentage area and average phase shift, respectively). CONCLUSIONS: Higher iron deposition in the putamen and PT may differentiate MSA-P from IPD, but the lower inner region of the putamen may be better compared with the PT and other subregions of the putamen. Moreover, the high iron percentage makes it possible to detect smaller increases in iron content more confidently in comparison with average phase shift. PMID- 22051808 TI - Combined endovascular and surgical approach for the treatment of palpebral arteriovenous malformations: experience of a single center. AB - BACKGROUND AND PURPOSE: Palpebral AVMs (pAVMs) are rare vascular lesions for which the treatment is challenging. Our aim was to present the technical aspects of the presurgical treatment by interventional neuroradiology of pAVMs and to report the clinical and angiographic results of combined (interventional neuroradiology/surgery) treatment of these malformations. MATERIALS AND METHODS: Nine patients (5 females, 4 males) with a mean age of 22 years (range, 12-35 years) were treated in our department from December 1992 to April 2007 for superficial pAVMs. Seven patients presented with isolated pAVMs, while 2 had hemifacial AVMs. Ten TAE procedures, by using a liquid embolic agent (glue or Onyx) or microparticles, were performed in 7 patients. Six patients underwent absolute alcohol, glue, or sclerotic agent injection by direct puncture in 8 procedures. Clinical and angiographic follow-up were performed with a mean delay of, respectively, 6.3 and 5 years. RESULTS: Three patients had a single EVT. Iterative procedures were performed in 5 patients. In 1 patient, EVT was not performed because of the risk of occlusion of the central retinal artery. No complication occurred except 1 case of transient palpebral hematoma. No visual acuity loss related to an endovascular procedure was reported. Exclusion of the AVMs at the end of the procedure was >75% in all cases and total in 3/8 cases. All the patients except 2 underwent at least 1 surgical procedure after the embolization. Good clinical regression of the mass was obtained in all patients at long-term follow-up. CONCLUSIONS: Combined endovascular and surgical treatment of pAVMs is an effective and safe technique with good clinical results at long term follow-up. PMID- 22051809 TI - Utility and interobserver agreement of ultrasound elastography in the detection of malignant thyroid nodules in clinical care. AB - BACKGROUND AND PURPOSE: Malignancy correlates with hardness of tissues and US elastography can potentially analyze the stiffness of lesions. Our aim was to evaluate the utility of US elastography in the detection of malignant nodules and to investigate interobserver agreement with this technique. MATERIALS AND METHODS: One-hundred three consecutive patients with 106 thyroid nodules were examined prospectively with conventional B-mode sonography and real-time US elastography. All patients were referred for FNAB. Conventional B-mode sonography and US elastographic examinations were performed, and images were separated and independently interpreted by 2 radiologists blinded to pathologic results. US elastogram evaluation was based on a simplified classification of stiffness based on gray-scale patterns, tumor size compared with B-mode, and margins. Interobserver agreement was studied. FNAB was used as the reference standard for the diagnosis of benign nodules, but histopathologic evaluations were performed when results suspicious for malignancy or malignant results were obtained on FNAB as well as in indeterminate lesions. RESULTS: In our study, pattern of stiffness based on gray-scale and classification proposed were statistically significant and predicted malignancy with 100% sensitivity and 40.6% specificity. Tumor size when compared with B-mode images or margins was not statistically significant in our study. No false-negatives were found, and an NPV of 100% was seen. Interobserver agreement for US elastography was excellent in our study, with a kappa index of 0.82 (95% CI). CONCLUSIONS: We believe that US elastography is a promising technique that can assist in the evaluation of thyroid nodules and can potentially diminish the number of FNAB procedures needed. We believe that it may be useful to introduce US elastography into routine clinical practice. PMID- 22051810 TI - Modeling MR imaging enhancing-lesion volumes in multiple sclerosis: application in clinical trials. AB - BACKGROUND AND PURPOSE: Although the number of enhancing lesions is the typical outcome measure of choice in clinical trials in MS, a potentially more sensitive and statistically more powerful outcome measure is the volume of enhancing lesions. In this study, we assessed the distribution and statistical power of the volume of enhancing brain lesions as an outcome measure by means of their required sample size, and we compared the results with the number of enhancing lesions. MATERIAL AND METHODS: First, a literature search was performed to compare the effects of treatment on the number and volume of enhancing lesions. Then, a statistical model was proposed to describe the distribution of the volume of enhancing lesions in 2 datasets of patients with RRMS, and sample sizes for enhancing-lesion volume as primary outcome measure were calculated. RESULTS: A mixture of the binomial and Weibull distribution was determined to model enhancing-lesion volumes in patients. Sample size calculations for enhancing lesion volumes showed that approximately 94 patients per arm would be required to detect a combination of 20% decrease in lesion volume and 20% increase in patients without enhancing lesions, whereas calculations for enhancing-lesion counts showed that approximately 129 patients would be required to detect a 50% decrease. CONCLUSIONS: The mixture of the binomial and Weibull distribution is a suitable approach in modeling new enhancing-lesion volumes in MS and yielded feasible sample size estimates for clinical trials, showing lesion volumes to be an advantageous outcome measure compared with lesion counts in terms of statistical power. PMID- 22051811 TI - The lumbar multifidus muscles are affected by medial branch interventions for facet joint syndrome: potential problems and proposal of a pericapsular infiltration technique. PMID- 22051812 TI - Positional venous MR angiography: an operator-independent tool to evaluate cerebral venous outflow hemodynamics. AB - BACKGROUND AND PURPOSE: CCSVI has been proposed as a cause for MS. According to this theory, strictures of the IJV are among the described causes for CCSVI. Little is known about their influence on the hemodynamics of the CVBO. We used positional MR imaging to describe the influence of positional changes on the CVBO. MATERIALS AND METHODS: Using the Fonar Upright MR imaging system, we performed venous time-of-flight angiography of the cervical region in the supine and sitting positions in 15 healthy volunteers. The image quality was rated; the positional findings and interindividual variances in the CVBO were analyzed. RESULTS: A venous time-of-flight angiography of the cervical spine was feasible with good image quality. Strictures of 1 or both IJVs were found in 8 of 15 healthy volunteers in the supine position; however, none were visible in upright position. The IJV was not the main outflow route in the erect position. No relevant venous reflux was observed. CONCLUSIONS: IJV strictures are a common finding in healthy volunteers in the supine position. They seem to be of no relevance in the erect position. This finding questions the validity of this criterion for the diagnosis of CCSVI. Reflux into the venous system was not visualized, and it remains to be seen whether it can be identified in patients with MS. Positional MR imaging enables operator-independent evaluation of the CVBO and may help to clarify the validity of the criteria for CCSVI. PMID- 22051813 TI - Simultaneous arteriovenous shunting and venous congestion identification in dural arteriovenous fistulas using susceptibility-weighted imaging: initial experience. AB - In this short report, we describe the potential contribution of SWI in the noninvasive evaluation of DAVFs. SWI images were compared with DSA for the identification of the location of the fistulous point, the presence of CVR, and the presence of the PPP. In 5 of 6 patients, it was possible to identify the fistulous locations depicted as hyperintensity within venous structures. Cortical venous reflux was underestimated on SWI in 3 cases of robust CVR and not identified in 2 cases of less severe CVR. The PPP seen on angiograms correlated anatomically with increased number, caliber, and tortuosity of hypointense veins seen on SWI. Furthermore, SWI was superior to conventional MR imaging in the detection of these dilated veins. These preliminary results suggest an important role for SWI in the detection and assessment of the complex hemodynamics associated with DAVFs. PMID- 22051814 TI - Unilateral hypoplasia of the rostral end of the superior sagittal sinus. AB - BACKGROUND AND PURPOSE: Hypoplasia of the rostral third of the SSS is a well known variant and constitutes the most frequent variation of the SSS after preferential drainage to one of the transverse sinuses. Our aim was to describe unilateral hypoplasia of the rostral end of the SSS. MATERIALS AND METHODS: CTA performed in 100 consecutive patients studied for conditions other than dural sinus thrombosis was reviewed for the presence of a unilateral or bilateral hypoplastic rostral SSS. Associated dural venous sinus anomalies were recorded as well. The angiographic anatomy of unilateral hypoplastic rostral SSS was illustrated by 2 cases further imaged with DSA. RESULTS: Unilateral hypoplastic rostral SSS was found in 7 patients (7%). In all cases, compensatory drainage occurred through a large superior frontal vein that joined the SSS in the region of the coronal suture. Three of the 7 patients with a unilateral hypoplastic rostral SSS had at least another dural venous sinus anomaly. Complete or bilateral hypoplastic rostral SSS was noted in 3 patients (3%). CONCLUSIONS: Unilateral hypoplastic rostral SSS is more than twice as frequent as bilateral hypoplastic rostral SSS. It is the most frequently encountered variation of the SSS. Knowledge of this anatomic variation is important to avoid diagnostic pitfalls and to avoid erroneously mistaking it for a thrombosis. Four types of variations of the rostral SSS may be identified: 1) classic anatomy with a fully developed rostral SSS; 2) duplication of the rostral SSS; 3) complete or bilateral hypoplastic rostral SSS; 4) unilateral hypoplastic rostral SSS. The 4 types of rostral SSS variations can be explained by studying the embryologic development of the SSS. PMID- 22051815 TI - Morbidity following primary cesarean delivery in the Danish National Birth Cohort. AB - OBJECTIVE: Cesarean delivery rates are on the rise in many countries, including the United States. There is mounting evidence that cesarean delivery is associated with adverse reproductive outcomes in subsequent pregnancies. The purpose of this article is to review those outcomes in a well-defined cohort of pregnant women. STUDY DESIGN: In a cohort of primigravid women from the Danish National Birth Cohort with known baseline exposure characteristics, we stratified women by method of first delivery, vaginal or cesarean, and evaluated for appearance of adverse reproductive events in subsequent pregnancies. RESULTS: After adjusting for age, body mass index, alcohol, smoking, and socioeconomic status, women who underwent cesarean delivery at first birth were at increased risk in their subsequent pregnancy for anemia (odds ratio [OR], 2.8; 95% confidence interval [CI], 2.3-3.4), placental abruption (OR, 2.3; 95% CI, 1.5 3.6), uterine rupture (OR, 268; 95% CI, 65.6-999), and hysterectomy (OR, 28.8; 95% CI, 3.1-263.8). CONCLUSION: Women who deliver their first baby with a cesarean are at increased risk of adverse reproductive outcomes in subsequent pregnancies and should be counseled accordingly. PMID- 22051816 TI - Inverted balloon vaginoplasty: an obstructed upper vaginal pouch was pulled downward to form a neovagina. AB - Inverted balloon vaginoplasty technique was performed for a case with segmental vaginal aplasia and upper hematocolpos within 50 min operative time without any complications. The neovagina was naturally covered, 11 cm in depth and communicated with dimple at hymen's site. Regular painless menstruations were reported. PMID- 22051817 TI - Resuscitation of likely nonviable infants: a cost-utility analysis after the Born Alive Infant Protection Act. AB - OBJECTIVE: The purpose of this study was to compare the effects of universal vs selective resuscitation on maternal utilities, perinatal costs, and outcomes of preterm delivery and termination of pregnancy at 20-23 weeks 6 days' gestation. STUDY DESIGN: We used studies on medical practices, prematurity outcomes, costs, and maternal utilities to construct decision-analytic models for a cohort of annual US deliveries after preterm delivery or induced termination. Outcome measures were (1) the numbers of infants who survived intact or with mild, moderate, or severe sequelae; (2) maternal quality-adjusted life years (QALYs); and (3) incremental cost-effectiveness ratios. RESULTS: Universal resuscitation of spontaneously delivered infants between 20-23 weeks 6 days' gestation increases costs by $313.1 million and decreases QALYs by 329.3 QALYs; after a termination, universal resuscitation increases costs by $15.6 million and decreases QALYs by 19.2 QALYs. With universal resuscitation, 153 more infants survive: 44 infants are intact or mildly affected; 36 infants are moderately impaired, and 73 infants are severely disabled. CONCLUSION: Selective intervention constitutes the highest utility and least costly treatment for infants at the margin of viability. PMID- 22051818 TI - [Tuberculosis: steady dynamics between past and present to imagine the future]. AB - Progress in understanding the biological processes that allow Mycobacterium tuberculosis to be a successful parasite have accelerated in the last twenty years. This progress has been stimulated by the return of tuberculosis (TB) as an important disease in industrialized countries, by its increase in emergent nations in the tail of population increases and poverty and by the spread of multiple drug resistant (MDR) and extensively drug resistant (XDR) M. tuberculosis as a result of treatment failures. Progress on M. tuberculosis biology has also been fueled by advances in microbiology and molecular biology, including molecular genetics, genomics, proteomics and in vitro and in vivo models of infection. The study of latency or dormancy, a phenomenon central to understanding the persistence of M. tuberculosis and the development of TB in individuals, its spread in human populations and the emergence of antibiotic resistant/tolerant organisms, has been preferred targets for investigators in this area. In this manner, factors that trigger M. tuberculosis latency (e. g, hypoxia, nutrient starvation, NO exposure) have been characterized and the metabolic shifts to host lipid utilization, tolerance to antimicrobials and resistance to host immune mechanisms involved in latency have been determined. Similarly, genetic changes and the resulting antimicrobial mechanisms mediating the MDR and XDR states have been characterized and potential new vaccines that avoid reactivation from latency and infection are being developed. Despite this progress, and given the fact that effective anti tuberculosis therapy was developed and first introduced clinically at the end of the 1940s, there are now more cases of latent and active TB worldwide than ever before. This reinforces the concept of TB as a bacterial disease with strong social and economical! determinants which are presently stimulating increased transmission in many human groups, undermining diagnostics, treatment and prevention. It suggests that in a scenario of global economical crisis the struggle against TB will be weakened, unless efforts are included to alleviate poverty, decrease economic inequality, improve public health and allow democracy and political organization. PMID- 22051819 TI - [Genetic characterization of the virus causing H1N1 influenza pandemic in Chile: analysis of the first detected cases]. AB - BACKGROUND: Following the announcement of the Influenza A(H1N1) pandemic by the World Health Organization in April 2009, a surveillance program was carried out in Chile to detect the introduction of the virus in the country and to monitor its propagation and impact. AIM: To describe the onset of the outbreak and the genetic characterization of the pandemic H1N1 influenza virus in the first detected cases in Chile. MATERIAL AND METHODS: Analysis of18 clinical samples coming from suspicious patients, received in a National Reference Laboratory. RNA reverse transcription and real time influenza gene DNA amplification was carried out in a 7500 Fast and Step One Real Time PCR Systems of Applied Biosystems and MxPro-Mx3000P thermocycler from Stratagene. Super Script III Platinum One-Step Quantitative RT-PCR was used. RESULTS: The virus was first detected in three persons returning from the Dominican Republic via Panama and a child from the east zone of Santiago. Genetic characterization of the virus showed that the child was infected by a different variant of the pandemic virus than the three persons returning from the Caribbean. CONCLUSIONS: The onset of the Influenza outbreak in Chile apparently carne from two different epidemiological groups. The spread of the virus detected in the voyagers was limited immediately However the virus of the fourth case was found in different regions of Chile. PMID- 22051820 TI - [A national online survey applied to patients with celiac disease in Chile]. AB - BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Its prevalence in Europe and the USA is 0.5 to 1%. AIM: To analyze epidemiological aspects and degree of compliance with gluten-free diet (GFD) among Chilean individuals with CD. MATERIAL AND METHODS: Subjects with confirmed or suspected CD were invited to answer an online survey published on the web at www.fundacionconvivir.cl. The answers were reinforced with a telephone interview. RESULTS: The survey was answered by 1212 subjects (79% females). Median age at diagnosis was 25.8 years (range 1 to 84 years), with a bimodal curve with two peaks at less than 3 years and at 20 to 40 years of age. The diagnosis was made only by serologic markers in 9%, only by intestinal biopsy in 17.5%, and by a combination of both methods in 70%o. Conditions associated with CD were reported by 30% > of subjects and 20% > had relatives with CD. The GFD was strictly adhered to by 70% >, occasionally by 27% > and never by 3% >. Seventy five percent of subjects with a strict adherence to GFD had a favorable clinical response compared with 42% > of those with incomplete or lack of adherence (odds ratio 4.0, 95% > confidence intervals 2.8 5.7p < 0.01). CONCLUSIONS: In 30% of respondents, the diagnosis of CD was not confirmed according to international guidelines that require serology and duodenal biopsy. One third of subjects recognized a poor compliance with GFD. Those with a strict adherence to it had a more favorable clinical course. However, 25% > did not experience a clinical improvement despite a strict GFD, a finding which requires further study. PMID- 22051821 TI - [Competences on hypoglycemia management among healthcare professionals in a clinical hospital]. AB - BACKGROUND: A tight glycemic control of hospitalized patients increases the risk of hypoglycemia, whose management is not always optimal. AIM: To assess the hypoglycemia management competences of a multidisciplinary team in a clinical hospital. MATERIAL AND METHODS: An anonymous questionnaire about hypoglycemia management was answered by 11 staff physicians, 42 residents and 28 nurses of the department of medicine and critical care unit ofa university hospital. RESULTS: Respondents had a mean of 60% of correct answers, without significant differences between groups. The capillary blood glucose level that defines hypoglycemia was known by most of the respondents, but the value that defines severe episodes was known only by 60%. The initial management and follow up was well known only for severe episodes. Less than 50%o knew the blood glucose value that required continuing with treatment. CONCLUSIONS: Although most professionals are able to recognize hypoglycemia, the knowledge about is management if insufficient. PMID- 22051822 TI - [Prevalence of the drug consumption among Chilean university students]. AB - BACKGROUND: Drug abuse is one of the main public health problems and mostly involves young people. AIM: To determine the prevalence of drug consumption among university students and its associated social factors. MATERIAL AND METHODS: A questionnaire exploring consumption of drugs and social-demographic, economic and religious variables, was applied to 1577 third year students aged 22 +/- 2 years (54% females) of a public university. RESULTS: Sixty eight percent of the students were of middle socioeconomic class, 71 % belonged to some religion and 29% declared themselves as agnostic. Ninety six percent drank alcohol at least once and 29% never smoked. Among illicit drugs, marijuana was consumed by 22% followed by cocaine in 5.3%o, hallucinogenic drugs in 2.6 % >, inhalants in 2.3% > and cocaine free base in 1.4%). Six percent consumed stimulants and 13.8%>, sedatives. A higher economic income facilitated drug consumption and the adscription to a religion was protective against it. CONCLUSIONS: Alcohol is the most commonly consumed drug, and is the substance that generates more problems to students. PMID- 22051823 TI - [Non compaction cardiomyopathy: a series of 15 cases]. AB - BACKGROUND: Non compaction cardiomyopathy is a rare disorder caused by the arrest of myocardial compaction during embryogenesis, leading to a non compacted endocardial layer with marked hypertrabeculation and deep recesses. AIM: To report the clinical and echocardiographic characteristics of a series of 15 adult patients with non-compaction cardiomyopathy. PATIENTS AND METHODS: We included a total of 15 patients aged 52 +/- 17 years (40% males) diagnosed at our echocardiography laboratory between January 2001 and July 2010. RESULTS: The form of presentation was heart failure in 53% of subjects, syncope in 20%o, ventricular arrhythmias in 13%o and stroke in 7%>. Left ventricular end-diastolic diameter was 66 +/- 11 mm and estimated ejection fraction was 27 +/- 10%>. Apical and/or mid-ventricular segments of the left ventricle were involved in all the cases. Pulmonary hypertension was present in 40%o. The average follow-up was 19 months and no patient died during this period. Sixty seven percent of the patients had manifestations of heart failure, 27%o presented sustained ventricular arrhythmias and 20%> had atrial fibrillation or flutter, whereas 13%o had cerebral embolic events. An automated internal cardioverter defibrillator was implanted in 47%o of patients. CONCLUSIONS: Non-compaction cardiomyopathy is associated with high cardiovascular morbidity. The diagnosis is made in advanced stages of the disease, with significant dilation and ventricular dysfunction. PMID- 22051824 TI - [Prevalence of hypertension in school age children and its association with obesity]. AB - BACKGROUND: Hypertension in children is a frequently overlooked problem that is an important cardiovascular risk factor. AIM: To determine the prevalence of hypertension among school age children. MATERIAL AND METHODS: Cross-sectional study of 2980 children aged 10 +/- 2 years (48% females) from 10 schools of middle and lower class in Metropolitan Santiago. Blood pressure (BP) was measured in the sitting position on three occasions after a rest period, using a mercury sphygmomanometer with appropriate cuff arm diameter, averaging the results of the measurements. Systolic and diastolic hypertension were defined as blood pressure values over 95 percentile for age, sex and height. RESULTS: The overall prevalence of hypertension was 12.2% in women and 15% in men (p < 0.05). According to nutritional status, the prevalence was 6.7, 8.9,13.6 and 26% in underweight, eutrophic, overweight and obese children, respectively (p < 0.01). Compared with normal weight children, the risk of being hypertensive for overweight children was 1.6 (95% confidence intervals (CI) 1.2-2.3) and for obese children was 3.6 (95% CI 2.8-4.7). CONCLUSIONS: The studied children had a high prevalence of hypertension, that was directly related to a higher body mass index. PMID- 22051825 TI - [A study of hospital complaints and the role of the doctor-patient communication]. AB - BACKGROUND: Medical practice in Chile has changed dramatically over the last few years. Patients have raised their expectations and there is a growing number of complaints, and malpractice lawsuits. The doctor-patient relationship plays a fundamental role in patient satisfaction and has also been identified as an issue in most medical lawsuits. AIM: To analyze the importance of doctor-patient communication in the complaints received in a university hospital in Chile. MATERIAL AND METHODS: Review ofall complaints received at the office for quality of care at a university hospital. Complaints classified in delay, manners and information categories were selected for further analysis. RESULTS: Of a total of 8931 complaints registered between 2001 and 2008, 635 (19%) involved a doctor. Fifty one per cent of the latter, were related to the doctor-patient relationship. Of these, 146 cases (45%) were further classified as "Dysfunctional delivery of Information", 74 cases (23%) as "Not understanding the patient/'family's perspective", 54 cases (17%) as "Discrediting the patient or family's views" and 49 cases (15%) as "Lack of communication". CONCLUSIONS: The percentage of complaints related to communication with the doctor is high, though lower than cited in other studies. The most common complaint is the dysfunctional delivery of information. PMID- 22051826 TI - [Validation of the sino-nasal outcome test in Chile]. AB - BACKGROUND: Allergic rhinitis and sinusitis are common diseases that affect quality of life of pediatric and adult patients. AIM: To adapt and validate the Sino-Nasal Outcome Test 20 indicators (SNOT-20) survey in Chilean subjects. MATERIAL AND METHODS: In a psychometric validation study, an adapted version of the SNOT-20 adapted version was applied to 181 volunteers on two different occasions, three weeks apart. Feasibility (response time and perceived difficulty), reliability (internal consistency and test-retest) and validity (concurrent validity, correlating results with an independent instrument; predictive validity assessing its sensitivity to detect changes and discriminate validity, assessing receiver operating characteristic (ROC) curves), were assessed. An exploratory factor analysis was performed to confirm the presence of previously described underlying constructs. RESULTS: Eighty percent of participants considered SNOT-20 easy to complete. This task was completed in less than 5 minutes. Cronbach's alpha was 0.946. Temporal stability on a healthy subgroup was strong with an intraclass correlation coefficient of 0.92. SNOT-20 had a correlation coefficient of 0.82 with an independent instrument and its score significantly decreased after 3 weeks of treatment (p = 0.003). The area under ROC curve was 0.895. Factor analysis identified four principal components which possessed identical structure as previously described. CONCLUSIONS: SNOT-20 survey was valid, reliable and easy to implement among Chilean subjects. PMID- 22051827 TI - Screen viewing, body mass index, cigarette smoking and sleep duration in Belgrade University student population: results of an observational, cross-sectional study. AB - BACKGROUND: Subjects that spend more time working on computers or watching television could have a higher body mass index. AIM: To assess the relationship between time spent in front of a screen and studying, body mass index (BMI), smoking, and sleep duration among university students. MATERIAL AND METHODS: A cross-sectional study of 734 randomly selected students aged 21 +/- 2 years (450 females) that responded an anonymous, structured questionnaire about time spent watching television or in front of a computer, time spent studying, number of daily hours of sleep, smoking habits and number of daily meals. Body mass index was also calculated for all subjects RESULTS: Among males, the number of daily sleep hours, time spent working with computers and number of daily meals were significantly higher and time spent studying was significantly lower than females. Nonsmokers ate a significantly higher number of meals and spent less time watching television. No association was observed between time spent in front of a screen and number of sleep hours of body mass index. CONCLUSIONS: Men and smokers spend more time working in computers. There is no association between body mass index and time spent in front of screens. PMID- 22051828 TI - [Relative bioavailability study of two oral formulations of mycophenolate mofetil in healthy volunteers]. AB - BACKGROUND: The bioequivalence of different formulations of a same pharmaceutical product must be tested empirically. AIM: To evaluate the relative bioavailability for an oralformulation of mycophenolate mofetil (MMF) (LinfonexTM) compared to the reference formulation (CellceptTM) to determine the bioequivalence between both formulations. MATERIAL AND METHODS: A randomized, crossover, double-blind trial in 22 healthy male volunteers, who received a single oral dose of 1000 mg of Linfonex and Cellcept with a washout period of 10 days. Plasma levels of the drug were determined by high performance liquid chr ornatography. Plasma concentrations were plotted and maximum concentration, area under the plasma concentration versus time between 0 and 12 hours after administration and area under plasma concentration curve versus time after administration between 0 and infinity, were calculated for both products. RESULTS: The active compound, mycophenolic acid, was similarly absorbed in both formulations. No statistically significant differences were found in calculated pharmacokinetic parameters between both formulations. CONCLUSIONS: LinfonexTM 500 mg is bioequivalent to CellceptTM 500 mg. PMID- 22051829 TI - [Thalidomide for recurrent gastrointestinal bleeding caused by angiodysplasia: report of one case]. AB - Chronic hemodialysis patients may have recurrent bleeding from gastrointestinal angiodysplasia, that often is diffusely located in the digestive tract or in places difficult to reach with traditional endoscopes. Therefore, they cannot be locally treated or removed. We report a 70 years old man on chronic hemodialysis, with severe and persistent anemia due to bleeding from angiodysplasia of the small bowel. Despite administration of high doses of erythropoiesis stimulating agents, intravenous iron, folate, B6 and B12 vitamins, his hemoglobin levels were < 6.5 g/dL, becoming totally dependent on transfusions of red blood cells (up to 46 units per year). Recurrent bleeding was refractory to conventional management and we decided to use thalidomide at doses of 50-100 mg/day achieving rapid control of gastrointestinal bleeding and significant increase of hemoglobin levels, not requiring further transfusions. PMID- 22051830 TI - [Myeloid sarcoma: report of one case with trisomy 11]. AB - Myeloid sarcoma is a form of extra-medullary myeloid neoplasia. Cytogenetic characterization is hampered in the absence of invasion to the bone marrow, origin of cells that are usually studied in cytogenetic studies. We report a 13 years old mole presenting with a mass in the right shoulder. A biopsy of the tumor disclosed a Myeloid Sarcoma. A conventional cytogenetic study of a bone marrow aspirate did not show t (8;21) translocation. A fluorescent in situ hybridization (FISH) performed in the paraffin embedded biopsy of the tumor, detected a chromosome 11 trisomy. PMID- 22051831 TI - [Twiddler syndrome: report of one case]. AB - We report a 26 year old patient who had a single chamber pacemaker implantation one year before. During a routine pre-operative evaluation, pacemaker dysfunction was demonstrated due to sensing and pacing failure, associated to left pectoral muscle rhythmic contraction. Chest X-ray confirmed Twiddler syndrome, in which twisting or rotation of the device inside the pocket results in lead dislodgement and device malfunction. PMID- 22051832 TI - [Live birth after the transfer of embryos obtained by fertilization of vitrified oocytes: report of one case]. AB - We report the first successful live birth after the transfer of embryos obtained by fertilization of vitrified oocytes. A couple with primary infertility due to teratozoospermy and chronic an ovulation decided to undergo assisted reproductive technology after 4 failed cycles of super ovulation and intrauterine insemination. The woman underwent a standard luteal phase agonist protocol, with controlled ovarian hyper stimulation with daily 150 IU recombinant gonadotropin and 75 IU urinary gonadotropin for 12 days. Due to the high risk of ovarian hyper stimulation syndrome the couple was advised to delay embryo transfer. Eighteen mature oocytes were recovered, eight were vitrified and 10 fertilized and cryopreserved as pro-nuclei. Two months later, four vitrified oocytes were thawed, and three morphologically-normal embryos were transferred to an estrogen progesterone-primed uterus, obtaining triple clinical pregnancy. The pregnancy was uneventful until 32 weeks of amenorrhea, when pre-term delivery started. After inducing lung maturity, a cesarean section was performed and three healthy fetuses were delivered. Nowadays, the babies are two and a half years old, and have had a normal psycho-motor development. PMID- 22051833 TI - [Quality of fat intake, atherosclerosis and coronary disease: effects of saturated and trans fatty acids]. AB - Epidemiological, clinical and metabolic research has shown a strong association between dietary fatty acids intake and cardiovascular disease (CVD) risk factors and clinical events. Saturated fatty acids (SFA) and trans fatty acids (TFA) derived from industrial hydrogenation of oils have been associated with an increased prevalence of CVD. However experimental results on the relationship between physiological pathologic effects and specific functions of individual SFA are often contradictory. Therefore a more detailed exploration of the potential benefit and risks of specific saturated and trans fatty acids is needed in order to update dietary recommendations. In the case of TFAs, the deleterious effect on CVD has been well demonstrated and a maximum accepted level of 1 % of total energy has been agreed internationally. What is currently under discussion is what would be the best alternative to replace them in the diet. PMID- 22051834 TI - [Sleep deprivation as a risk factor for obesity]. AB - Nocturnal sleep patterns may be a contributing factor for the epidemic of obesity. Epidemiologic ana experimental studies have reported that sleep restriction is an independent risk factor for weight gain and obesity. Moreover, sleep restriction is significantly associated with incidence and prevalence of obesity and several non-transmissible chronic diseases. Experimental sleep restriction is related to altered plasma leptin and ghrelin concentrations. Both hormones are directly related to appetite and satiety mechanisms. Also, a higher activity of the orexin/hypocretin system has been reported, as well as changes in glucose metabolism and autonomic nervous system. Some studies indicate that these endocrine changes could be associated with a higher diurnal food intake and preference for energy- dense foods. All these changes could result in a positive energy balance, leading to weight gain and a higher obesity risk in the long term. The present article summarizes the epidemiologic and experimental evidence related to sleep deprivation and higher obesity risk. The possible mechanisms are highlighted. PMID- 22051835 TI - [Applying positive psychology to medical education]. AB - Today we are witnessing an exponential growth in positive psychology (PP), a scientific approach to the most significant purpose of human existence: happiness and meaning of life. As a consequence of PP studies, happiness and wellbeing are now accepted as valid topics of research, despite their subjective and supposedly unscientific essence. Experimental evident indicates that happiness and wellbeing have biological bases and, thus, can be scientifically approached and eventually changed. We believe that we need to learn from this new discipline and apply its discoveries in our profession as medical educators to foster the full development of our students. In this review, we will summarize the major developments and discoveries of PP, and open the debate on the implications of PP offer to medical education. PMID- 22051837 TI - [Neruda and antimicrobial resistance]. AB - Antimicrobial resistance has been a problem in medicine, since their incorporation to clinical practice. Numerous papers have been written on the subject. The analysis of two poems by Pablo Neruda "How much does a man live" and "Larynx", included in the volume "Estravagario" and published for the first time in 1957 and 1958, give us an incredible revelation about the concept of resistance. In these poems aureomycin, the first antimicrobial of the family of tetracyclines, was included as a poetic figure and the therapeutic action of antimicrobials was described. "Never so much bugs died I tons of them fell I but the few that remained olive I manifested their perversity". These writings incorporated novel concepts, even for physicians of that time and described the closeness of death that a patient may perceive during the course of a given disease. The capacity of Pablo Neruda to extract the essence of situations and to anticipate to conditions that only years later became clinically relevant problems, is noteworthy. PMID- 22051838 TI - [Mental health of young offenders deprived of liberty: a pending debt]. PMID- 22051839 TI - [Flow sheet to evaluate Post Graduate Teaching Programs]. PMID- 22051840 TI - Direct ion-selective electrode method is useful in diagnosis of pseudohyponatremia. PMID- 22051841 TI - Small bowel obstruction from potato and broccoli phytobezoar mimicking mesenteric ischemia. AB - BACKGROUND: Bezoars are concretions of undigested foreign material that form in the gastrointestinal tract. Rare in humans, they are nonetheless a well documented cause of intraluminal bowel obstruction. OBJECTIVES: The objectives of this case report include describing an unusual presentation of small bowel obstruction due to phytobezoar, which mimicked mesenteric ischemia, and highlighting the risk factors, presentation, and management of bezoars, in addition to covering historical beliefs regarding bezoars. CASE REPORT: Here we report a 64-year-old man who presented to the Emergency Department with chest pain, vomiting, and hypotension. Initial work-up was directed at ruling out cardiac causes and aortic catastrophe such as aortic dissection or ruptured abdominal aortic aneurysm. Computed tomography angiography of the chest and abdomen showed findings suggestive of mesenteric ischemia and small bowel obstruction. However, exploratory laparotomy revealed intraluminal small bowel obstruction from a phytobezoar consisting of undigested chunks of potato, brussels sprouts, and broccoli. CONCLUSIONS: Although rare in humans, bezoars are a documented cause of small bowel obstruction, and should be considered when intraluminal bowel obstruction occurs. Bezoars causing small bowel obstruction require surgical treatment. PMID- 22051842 TI - A patient with massive localized lymphedema. PMID- 22051843 TI - Non-operative management in penetrating abdominal trauma: is it feasible at a Level II trauma center? AB - BACKGROUND: The recent mandate for surgical exploration for all penetrating abdominal trauma has been questioned. High-volume centers report good outcomes for non-operative treatment in penetrating trauma for hemodynamically stable patients without peritonitis and with tangential wounds. The applicability of this strategy in smaller hospitals is unknown. STUDY OBJECTIVES: The purpose of this study was to evaluate non-operative management of penetrating abdominal trauma at a Level II trauma center. METHODS: We retrospectively reviewed all patients with penetrating abdominal trauma from 2006 through 2008. Demographic information, treatments, and outcomes were analyzed using descriptive statistics. RESULTS: Our sample consisted of 86 patients with penetrating abdominal trauma; 12 (14%) had documented peritoneal violation and were managed non-operatively. The average age was 30 years (range 21-39 years), with 50% African American, 33% Caucasian, and 17% Hispanic. Male patients accounted for 92%, and the average Injury Severity Score was 5.2 (range 1-13). Overall non-operative treatment failed in 3 patients (25%); one required drainage of a retrogastric abscess on hospital day 4, and another underwent gastric and diaphragm repair on hospital day 1. The third treatment failure did not require an operation but developed a biloma requiring percutaneous drainage. There were no other complications related to non-operative therapy and no mortalities. The average length of stay was 3.9 days; 83% of patients were discharged home. CONCLUSIONS: In hemodynamically stable patients without peritonitis and documented isolated injuries to solid organs, non-operative management of penetrating abdominal trauma seems safe; however, it can delay diagnosis of hollow viscus injuries. Until further data emerge, extreme caution should be used in employing non-operative management for penetrating abdominal injuries at small trauma centers. PMID- 22051844 TI - Swabbing skin with alcohol could change the blood alcohol level significantly. PMID- 22051845 TI - A review on adherence management in patients on oral cancer therapies. AB - PURPOSE: There is currently an ongoing paradigm shift in cancer treatment from intravenous (IV) chemotherapeutics to oral therapies. Additionally, the increased use of long-term maintenance therapy with oral targeted agents or chemotherapy is contributing to a shift toward a chronic-disease model. This shift is creating challenges and responsibilities for health care professionals in patient adherence management. This article will inform health care professionals of current trends and describe ways that they can overcome common barriers to adherence. A comprehensive review of recommendations and evidence derived from oncological studies describing adherence to oral targeted therapies and maintenance chemotherapy will provide guidance for the use of emerging oral maintenance therapies. METHODS: Articles in the scientific literature were reviewed if published between January 1985 and November 2010. Searches were conducted using the PubMed database-search terms included "oral therapy," "chemotherapy," "cancer," and "adherence" or "compliance." RESULTS: The change from IV therapy administered and monitored in hospitals or clinics to self administered outpatient oral treatments decreases the likelihood of adherence. Methods, such as patient education and monitoring and involvement of family or caretakers, can improve adherence in patients undergoing treatment. CONCLUSIONS: At treatment onset, oncology nurses can engage patients directly in a collaborative dialogue, and when issues affecting adherence arise, oncology nurses may limit nonadherence by providing individually tailored educational material. A practical approach to patient education, along with building strong health care provider-patient relationships, can help patients overcome nonadherence to new oral anticancer therapies and treatment paradigms. PMID- 22051846 TI - Needs of relatives of breast cancer patients: the perspectives of families and nurses. AB - PURPOSE: Breast cancer is not only a stressful event for those afflicted, but also for their family and friends. In Germany, attention and support from professional nurses is almost exclusively given to the patient. But even relatives require information and support in order to keep their anxiety levels low and strength up. The aim of this study is to survey those needs and the current level of satisfaction, as well as to ascertain which needs are perceived by nurses. METHOD: Data were collected in a German-wide descriptive cross sectional study surveying 242 relatives and 356 nurses from 150 randomly chosen certified breast care centers between August 2008 and February 2009. Two questionnaires developed for this study were used. RESULTS: The findings indicate that relatives need above all a) security and trust, followed by b) partnership of care and c) emotional support. Regarding satisfaction, relatives consider the need for "security and trust" to be most satisfied. Least fulfilled were those for "partnership of care" and "emotional support". The nurses regarded the importance of most of the relatives' needs to be higher than the relatives themselves. Even the fulfillment of needs was over-estimated. CONCLUSIONS: The targeted and professional involvement of relatives in the care of breast cancer patients is still not common practice. An initial step toward better family nursing is viewing families as an integral part of the patient and intentionally planning contact. PMID- 22051847 TI - Interaction between Smad1 and p97/VCP in rat testis and epididymis during the postnatal development. AB - Members of the bone morphogenetic proteins (BMPs) superfamily are expressed in the testis and epididymis and are believed to have different biological functions during testicular and epididymal development. Smad1 is one of the signal transducers of BMP signaling and binds to several proteins involved in ubiquitin proteasome system (UPS). Valosin-containing protein (p97/VCP) is required for the degradation of some UPS substrates. Although p97/VCP has been indicated in different cellular pathways, its association with BMP signaling in male reproductive system has not been elucidated. The aim of the present study was to investigate the cellular localization of Smad1, phospho-Smad1, and p97/VCP and the interaction of proteins in the postnatal rat testis and epididymis. Testicular and epididymal tissues from 5-, 15- and 60-day-old rats were examined by immunohistochemistry, immunofluorescence, Western blotting, and immunoprecipitation techniques. In 5-day-old rat testis, Smad1, phospho-Smad1, and p97/VCP were mainly expressed in gonocytes. In 15- and 60-day-old rat testis, proteins were overlapped in spermatogonia, Sertoli cells, and spermatocytes. Expression of proteins in the epithelial cells of epididymis was gradually increased from 5 to 15 days of age. Smad1 and phospho-Smad1 expressions showed uniformity in the different regions of epididymis, however p97/VCP immunoreactivity was higher only in caput epididymis compared to corpus and cauda epididymis in 15- and 60-day-old rat epididymis. Co-immunoprecipitation experiments further confirmed the Smad1-p97/VCP and p-Smad1-p97/VCP interactions. The overlap between Smad1 and p97/VCP expressions in the postnatal rat testis and epididymis suggests that p97/VCP may play important roles in mediating BMP signaling during spermatogenesis. PMID- 22051848 TI - Reduced levels of serum pigment epithelium-derived factor in women with endometriosis. AB - The authors previously demonstrated decreased levels of pigment epithelium derived factor (PEDF) in peritoneal fluid of women with endometriosis compared to women without endometriosis. Here, the authors determine whether women with endometriosis have altered levels of PEDF in serum. Peripheral blood samples were collected from 71 women with and without endometriosis (n = 43 and 28, respectively) before laparoscopic surgery. Concentrations of serum PEDF were measured by enzyme-linked immunosorbent assay. We detected lower levels of serum PEDF in women with endometriosis (16.3 +/- 6.6 ng/mL) than in those without endometriosis (24.5 +/- 7.3 ng/mL; P < .001). In women with endometriosis, the concentrations of serum PEDF were significantly lower in women with pain (n = 11, 12.6 +/- 7.1 ng/mL) compared to women without pain (n = 32, 17.5 +/- 6.0 ng/mL; P < .05). However, the concentrations of serum PEDF did not correlate with disease stage or site or infertility. In addition, the concentrations of serum PEDF did not show any difference in the phase of the cycle in either group. Our results suggest that reduced levels of serum PEDF in women with endometriosis and disease related pain may play a role in the pathogenesis of this disease. PMID- 22051849 TI - Myocardial performance and its acute response to angiotensin II infusion in fetal sheep adapted to chronic anemia. AB - Fetal chronic anemia causes lengthening of cardiomyocytes. In adults, severe left ventricular overload may lead to irreversible ventricular dysfunction. We hypothesized that in sheep fetuses with chronic anemia, remodeled myocardium would less successfully respond to angiotensin II (AT II) infusion than in fetuses without anemia. A total of 14 ewes with twin pregnancy underwent surgery at 113 +/- 1 days of gestation. After a recovery period, anemia was induced by isovolumic hemorrhage in 1 fetus of each pair. At 126 +/- 1 days of gestation, longitudinal myocardial velocities of the right (RV) and left (LV) ventricles were assessed at the level of the atrioventricular valve annuli via tissue Doppler imaging. Cardiac outputs were calculated by pulsed Doppler ultrasound. All measurements were performed at baseline and during fetal AT II infusion. Fetal serum cardiac natriuretic peptide (N-terminal peptide of proatrial natriuretic peptide [NT-proANP] and B-type natriuretic peptide [BNP]) concentrations were determined. Nine ewes successfully completed the experiment. At baseline, ventricular free wall thicknesses, cardiac outputs, and NT-proANP levels were significantly greater in the anemic fetuses than in the controls. The LV isovolumic contraction velocity (IVCV) acceleration and isovolumic relaxation velocity (IVRV) deceleration were lower (P < .05) in the anemic fetuses than in the controls. In the anemic fetuses, there was a positive correlation (R = .93, P < .01) between RV IVRV deceleration and NT-proANP concentration. Angiotensin II infusion increased (P < .05) LV IVCV acceleration in the anemic fetuses. We conclude that in anemic sheep fetuses, myocardial adaptation is associated with impaired LV early contraction and relaxation. However, the LV can improve its contractility with an inotropic stimulus, even in the presence of increased afterload. PMID- 22051850 TI - Aqueous fenugreek seed extract ameliorates adriamycin-induced cytotoxicity and testicular alterations in albino rats. AB - The present work studied the effect of fenugreek seed extracts on cytotoxicity and testicular damage induced by adriamycin (ADR) in albino rats. Administrating animals with ADR caused significant increase in the percentage of chromosomal aberrations, decreased the mitotic index, and induced DNA damage in bone marrow. Testes of ADR-treated rats showed many histopathological alterations and the number of sperm head abnormalities increased. Moreover, the concentration of malondialdehyde (MDA) increased and the activity of catalase (CAT) and superoxide dismutase (SOD) decreased in the testis. Treating animals with ADR and aqueous seed extracts of fenugreek led to an improvement in the cytogenetic effect and testicular alterations induced by ADR. Lipid peroxidation was reduced and the activities of CAT and SOD were increased. In conclusion, the results indicated that fenugreek seeds ameliorated the cytotoxicity and testicular alterations induced by ADR in albino rats and this may be mediated by its potent antioxidant effects. PMID- 22051851 TI - Temporal investigation of matrix metalloproteinases and their inhibitors in human cervicovaginal fluid in late pregnancy and labor. AB - Temporal expression of matrix metalloproteinase (MMP)-1, -2, -3, -7, -8, -9, -12, and -13, and tissue inhibitors of metalloproteinases (TIMPs)-1 and -2 in human cervicovaginal fluid (CVF) in term pregnancy and labor was investigated. Term parous women provided CVF samples that were grouped into labor, 1 to 3, 6 to 8, and 12 to 16 days before labor onset. Both MMPs and TIMPs (n = 60) were quantified using multiplex solution array and enzyme-linked immunosorbent assays, respectively. Further analysis of TIMP-1 (n = 180) was undertaken. All MMPs and TIMPs except MMP-12 and -13 were detected in the CVF. Matrix metalloproteinase 7, TIMP-1, and TIMP-2 were significantly increased in labor. Tissue inhibitors of metalloproteinase 1 was significantly increased up to 7 days before spontaneous labor onset. The data suggest a role of MMP-7 in the remodeling and rupture of fetal membranes and may reflect the homeostatic regulation of extracellular matrix remodeling of MMP-7 by TIMP-1 and TIMP-2. PMID- 22051852 TI - Effects of residual antibiotics in groundwater on Salmonella typhimurium: changes in antibiotic resistance, in vivo and in vitro pathogenicity. AB - An outbreak-causing strain of Salmonella enterica serovar Typhimurium was exposed to groundwater with residual antibiotics for up to four weeks. Representative concentrations (0.05, 1, and 100 MUg L(-1)) of amoxicillin, tetracycline, and a mixture of several other antibiotics (1 MUg L(-1) each) were spiked into artificially prepared groundwater (AGW). Antibiotic susceptibility analysis and the virulence response of stressed Salmonella were determined on a weekly basis by using human epithelial cells (HEp2) and soil nematodes (C. elegans). Results have shown that Salmonella typhimurium remains viable for long periods of exposure to antibiotic-supplemented groundwater; however, they failed to cultivate as an indication of a viable but nonculturable state. Prolonged antibiotics exposure did not induce any changes in the antibiotic susceptibility profile of the S. typhimurium strain used in this study. S. typhimurium exposed to 0.05 and 1 MUg L(-1) amoxicillin, and 1 MUg L(-1) tetracycline showed hyper virulent profiles in both in vitro and in vivo virulence assays with the HEp2 cells and C. elegans respectively, most evident following 2nd and 3rd weeks of exposure. PMID- 22051853 TI - Role of CYP2E1-mediated metabolism in the acute and vestibular toxicities of nineteen nitriles in the mouse. AB - Allylnitrile, cis-crotononitrile, and 3,3'-iminodipropionitrile are known to cause vestibular toxicity in rodents, and evidence is available indicating that cis-2-pentenenitrile shares this effect. We evaluated nineteen nitriles for vestibular toxicity in wild type (129S1) and CYP2E1-null mice, including all the above, several neurotoxic nitriles, and structurally similar nitriles. A new acute toxicity test protocol was developed to facilitate evaluation of the vestibular toxicity by a specific behavioral test battery at doses up to sub lethal levels while using a limited number of animals. A mean number of 8.5+/-0.3 animals per nitrile, strain and sex was necessary to obtain evidence of vestibular toxicity and optionally an estimation of the lethal dose. For several but not all nitriles, lethal doses significantly increased in CYP2E1-null mice. The protocol revealed the vestibular toxicity of five nitriles, including previously identified ototoxic compounds and one nitrile (trans-crotononitrile) known to have a different profile of neurotoxic effects in the rat. In all five cases, both sexes were affected and no decrease in susceptibility was apparent in CYP2E1-null mice respect to 129S1 mice. Fourteen nitriles caused no vestibular toxicity, including six nitriles tested in CYP2E1-null mice at doses significantly larger than the maximal doses that can be tested in wild type animals. We conclude that only a subset of low molecular weight nitriles is toxic to the vestibular system, that species-dependent differences exist in this vestibular toxicity, and that CYP2E1-mediated metabolism is not involved in this effect of nitriles although it has a role in the acute lethality of some of these compounds. PMID- 22051854 TI - DNA, protein binding, cytotoxicity, cellular uptake and antibacterial activities of new palladium(II) complexes of thiosemicarbazone ligands: effects of substitution on biological activity. AB - The coordination propensities of 4(N,N')-diethylaminosalicylaldehyde-4(N) substituted thiosemicarbazones (H(2)L(1-4)) were investigated by reacting with an equimolar amount of [PdCl(2)(PPh(3))(2)]. The new complexes were characterized by various spectroscopic techniques. The structure determination of the complexes [Pd(DeaSal-tsc)(PPh(3))] (1), [Pd(DeaSal-mtsc)(PPh(3))] (2) and [Pd(DeaSal etsc)(PPh(3))] (3) by X-ray crystallography showed that ligands are coordinated in a dibasic tridentate ONS donor fashion forming stable five and six membered chelate rings. The binding ability of complexes (1-4) to calf-thymus DNA (CT DNA) has been explored by absorption and emission titration methods. Based on the observations, an electrostatic and an intercalative binding mode have been proposed. The protein binding studies have been monitored by quenching of tryptophan and tyrosine residues in the presence of complexes using lysozyme as a model protein. As determined by MTT assays, complex 3 exhibited a higher cytotoxic effect towards human lung cancer cell line (A549) and liver cancer cells (HepG2). LDH, NO assay and cellular uptake of the complexes have been studied. Further, antibacterial activity studies of the complexes have been screened against the pathogenic bacteria such as Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, MIC50 values of the complexes showed that the complexes exhibited significant activity against the pathogens and among the complexes, 3 exhibited higher activity. PMID- 22051855 TI - Anion-templated self-assembly of highly stable Fe(II) pentagonal metallacycles with short anion-pi contacts. AB - The crystal structures of the self-assembled metallapentacycles [{Fe(5)(bptz)(5)(CH(3)CN)(10)} ? 2SbF(6)][SbF(6)](8) (1) and [{Fe(5)(bmtz)(5)(CH(3)CN)(10)} ? SbF(6)][SbF(6)](9) (2) with the pi-acidic ligands bptz (3,6-bis(2-pyridyl)-1,2,4,5-tetrazine) and bmtz (3,6-bis(2 pyrimidyl)-1,2,4,5-tetrazine), respectively, revealed cationic pentagons templated by [SbF(6)](-) ions. The short anion-pi contacts established between the anions and the tetrazine rings play an important role in the stability of the pentagons. PMID- 22051856 TI - Effects of demographic structure on key properties of stochastic density independent population dynamics. AB - The development of stochastic demography has largely been based on age structured populations, although other types of demographic structure, especially permanent and dynamic heterogeneity, are likely common in natural populations. The combination of stochasticity and demographic structure is a challenge for analyses of population dynamics and extinction risk, because the population structure will fluctuate around the stable structure and the population size shows transient fluctuations. However, by using a diffusion approximation for the total reproductive value, density-independent dynamics of structured populations can be described with only three population parameters: the expected population growth rate, the environmental variance and the demographic variance. These parameters depend on population structure via the state-specific vital rates and transition rates. Once they are found, the diffusion approximation represents a substantial reduction in model complexity. Here, we review and compare the key population parameters across a wide range of demographic structure, from the case of no structure to the most general case of dynamic heterogeneity, and for both discrete and continuous types. We focus on the demographic variance, but also show how environmental stochasticity can be included. This study brings together results from recent models, each considering a specific type of population structure, and places them in a general framework for structured populations. Comparison across different types of demographic structure reveals that the reproductive value is an essential concept for understanding how population structure affects stochastic dynamics and extinction risk. PMID- 22051857 TI - A fluorescence-based assay for N-myristoyltransferase activity. AB - N-myristoylation is the irreversible attachment of a C(14) fatty acid, myristic acid, to the N-terminal glycine of a protein via formation of an amide bond. This modification is catalyzed by myristoyl-coenzyme A (CoA):protein N myristoyltransferase (NMT), an enzyme ubiquitous in eukaryotes that is up regulated in several cancers. Here we report a sensitive fluorescence-based assay to study the enzymatic activity of human NMT1 and NMT2 based on detection of CoA by 7-diethylamino-3-(4-maleimido-phenyl)-4-methylcoumarin. We also describe expression and characterization of NMT1 and NMT2 and assay validation with small molecule inhibitors. This assay should be broadly applicable to NMTs from a range of organisms. PMID- 22051858 TI - Revisiting crowd-out update. AB - Crowd-out occurs when the existence of public insurance causes people to shift from private to public coverage, thus stretching scarce government resources to insure those who could access private plans. This update looks at the research published since the 2004 synthesis was released. Key findings include: Some level of crowd-out will always occur with public program expansions. There is a wide range of estimates of crowd-out with lower estimates for low-income children (0 to 15%) and higher rates for higher-income children and longer-term enrollees (35% to 50%). Recent studies confirm the most common anti-crowd-out measures- waiting periods and increased public-plan premiums--discourage both the uninsured and the privately insured from enrolling in public coverage. Crowd-out is more likely when eligibility is expanded to include higher-incomes and entire families. Crowd out can occur based on employers', as well as employees' behaviors, but it appear the recent decline in ESI is more a result of employee take-up rather than employers dropping health benefits. Finally, there is limited research that suggests children with public coverage are better off than those with private insurance. PMID- 22051859 TI - Point-of-care capillary blood lactate measurements in human immunodeficiency virus-uninfected children with in utero exposure to human immunodeficiency virus and antiretroviral medications. AB - OBJECTIVES: To estimate the prevalence of elevated point-of-care (POC) capillary blood lactate concentrations in human immunodeficiency virus (HIV)-exposed, uninfected children (HEU) and to determine if POC lactate varies with in utero antiretroviral (ARV) exposure. METHODS: The Surveillance Monitoring for Antiretroviral Therapy Toxicities protocol of the Pediatric HIV/AIDS Cohort Study enrolled 1934 children between 2007 and 2009, 0 to 12 years of age, born to HIV infected mothers. POC lactate was measured annually on capillary blood using the Lactate Pro device. Associations of POC lactate with in utero ARV exposure and other characteristics were evaluated using logistic regression models, adjusting for maternal characteristics and other confounders. RESULTS: Of 1641 children with POC measurements (median age, 3.0 years), 3.4% had POC lactate >3 mmol/L. Median POC lactate level decreased with age (1.9 mmol/L, 1.7 mmol/L, and 1.6 mmol/L for children 0-<6 months [99% <=6 weeks of life], 6-<24 months, and >=24 months of age, respectively; P < 0.001). Prevalence of elevated POC lactate did not differ by in utero ARV exposure drug class, but was significantly higher in children exposed in utero to emtricitabine or efavirenz, cocaine or opiates, and those of white race. CONCLUSIONS: POC lactate testing is a useful rapid laboratory screening assay for HEU children with ARV exposure. ARV use during pregnancy has resulted in a dramatic decrease in mother-to-child transmission of HIV, and the risk of elevated lactate in HEU children is low. However, as new ARVs and more complex regimens are used during pregnancy by HIV-infected women, continued monitoring for infant toxicities is essential. PMID- 22051860 TI - Prevalence and genetic diversity of nontypeable haemophilus influenzae in the respiratory tract of infants and primary caregivers. AB - BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) causes otitis media, sinusitis, and likely lower respiratory tract infections in children. Colonization, strain diversity, transmission, and antimicrobial susceptibility have implications for both children and their caregivers. METHODS: For 13 months, we conducted a cross-sectional study of NTHi colonization. Upper respiratory tract cultures were performed in 273 infants and children 2 to 26 months of age and their primary caregivers. NTHi isolates were characterized by multilocus sequence typing (MLST), and antibiotic resistance was examined. RESULTS: Of the 273 infants, 44 (16.1%) were colonized with NTHi. Prevalence of NTHi varied from 14% in infants less than 6 months of age to 32% in infants between 19 and 26 months of age (P = 0.003). NTHi-colonized infants were more likely to attend day care (30% vs. 12%), have a recent respiratory infection (68% vs. 38%), have recently taken an antibiotic (27% vs. 9%), and have a primary caregiver who reported asthma (11% vs. 1%), compared with other infants (P < 0.01). In the 44 infants colonized with NTHi, we identified 33 different MLSTs. Of the 44 infant primary caregiver dyads, 9 (20.5%) were colonized with NTHi, and 7 of these 9 shared identical NTHi strains. We also found beta-lactamase-negative NTHi with minimum inhibitory concentrations >2 MUg/mL for amoxicillin and beta-lactamase positive NTHi with minimum inhibitory concentrations >2 MUg/mL for amoxicillin clavulanate. CONCLUSIONS: We found substantial diversity by MLST analysis among NTHi isolates from this community. Infant-primary caregiver dyads usually carried the same strain of NTHi, suggesting that infant-primary caregiver transmission is occurring. PMID- 22051861 TI - The BIO-PIN paradigm: 'access to' or 'return of' results? PMID- 22051863 TI - Impact of practice patterns in shunt use during carotid endarterectomy with contralateral carotid occlusion. AB - PURPOSE: This study investigated the association between surgeon practice pattern in shunt placement and 30-day stroke/death in patients undergoing carotid endarterectomy (CEA) with contralateral carotid occlusion (CCO). METHODS: Among 6379 CEAs performed in the Vascular Study Group of New England (VSGNE) between 2002 and 2009, we identified 353 patients who underwent CEA with CCO and compared the 30-day stroke/death rate with 5279 patients who underwent primary, isolated CEA with a patent contralateral carotid artery. Within patients with CCO, we examined the 30-day stroke/death rate across the reason for shunt placement and two distinct surgeon practice patterns in shunt placement: surgeons who selectively used a shunt (<=95% of CEAs) or routinely used a shunt (>95% of CEAs). We used observed/expected (O/E) ratios to provide risk-adjusted comparisons across groups. RESULTS: Of 353 patients with CCO, 118 (33%) underwent CEA without a shunt, 173 (49%) underwent CEA using a shunt placed routinely, and 62 (18%) had a shunt placed for a neurologic indication. Rates of 30-day stroke/death across categories of reason for shunt use were no shunt, 3.4%; routine shunt, 4.0%; and shunt for indication, 4.8% (P = .891). The risk of 30 day stroke/death was higher for surgeons who selectively placed shunts (5.6%) in all their CEAs and lower for surgeons who routinely placed shunts (1.5%, P = .05). The risk of 30-day stroke/death was >1 in patients undergoing selective shunting (O/E ratio, 1.4; 95% confidence interval [CI], 1.1-1.7) and <1 for surgeons who placed shunts routinely (O/E ratio, 0.4; 95% CI, 0.2-0.9). Stroke/death rates were lowest when individual surgeons' intraoperative decisions reflected their usual pattern of practice: 1.5% stroke/death rate when "routine" surgeons placed a shunt, 3.4% when "selective" surgeons did not place a shunt, and 7.6% stroke/death rate for "selective" surgeons who placed a shunt (P = .05 for trend). CONCLUSIONS: The risk of 30-day stroke/death is higher in CEA in patients with CCO than with a patent contralateral carotid artery. Surgeons who place shunts selectively during CEA have higher rates of stroke/death in patients with CCO. This suggests that shunt use for CCO during CEA is associated with fewer complications, but only if the surgeon uses a shunt as part of his or her routine practice in CEA. Surgeons should preoperatively consider their own practice pattern in shunt use when faced with a patient who may require shunt placement. PMID- 22051864 TI - Statin therapy is associated with superior clinical outcomes after endovascular treatment of critical limb ischemia. AB - OBJECTIVE: The aim of this study was to determine if statin therapy improves clinical outcomes after endovascular intervention in patients with critical limb ischemia (CLI). METHODS: A retrospective review of all patients undergoing endovascular treatment for CLI was performed. Two groups were created according to whether they were receiving statin therapy at the time of intervention. Demographics, lesion morphology, overall mortality, primary and secondary patency, and limb salvage were compared between these groups. Analysis was performed using multivariate regression and Kaplan-Meier analysis. RESULTS: Between 2004 and 2009, 646 patients, 319 receiving statin therapy and 327 without, underwent an endovascular intervention for CLI. The statin group had significantly higher rates of diabetes mellitus, coronary artery disease, congestive heart failure, previous myocardial infarction, and coronary artery bypass grafting (P < .05). The two groups had similar lesion length, location, lesion type, TransAtlantic Inter-Society Consensus (TASC) classification, and primary procedure. At 24 months, the statin-treated group had higher rates of primary patency (43% vs 33%; P = .007), secondary patency (66% vs 51%; P = .001), limb salvage (83% vs 62%; P = .001), and overall survival (77% vs 62%; P = .038). Statin therapy was also independently associated with improved limb salvage by multivariate regression analysis (hazard ratio, 2.55; P < .001). CONCLUSIONS: Patients who were receiving statin therapy when they underwent interventions to treat CLI had significantly improved overall survival, primary and secondary patency, and limb salvage rates. Our findings suggest that statins should be part of the periprocedural treatment regimen and support further investigation into the beneficial effects of statins in patients undergoing endovascular treatment of CLI. PMID- 22051865 TI - Intimal sarcoma in an inflammatory aneurysm after endovascular aneurysm repair. AB - Long-term outcomes after endovascular aneurysm repair (EVAR) for inflammatory aneurysms are unknown. We present a young patient with new-onset back pain and failure to thrive 6 years after EVAR for an inflammatory abdominal aortic aneurysm (AAA). Endograft explanation was performed with a presumed diagnosis of infection. Pathology revealed intimal sarcoma in the excluded aneurysm sac with liver metastasis. This report presents a detailed review of literature regarding potential association of prosthetic implantation and carcinogenesis. PMID- 22051866 TI - Leiomyosarcoma of the splenic vein. AB - Leiomyosarcomas are smooth muscle-derived tumors generally found intra abdominally in the retoperitoneum, mesentery, or omentum. Only approximately 5% of these tumors originate from vessel wall smooth muscle. Those derived from the splenic vein are exceedingly rare, with only one previously published case in the literature. We present a second case of leiomyosarcoma of the splenic vein in a 58-year-old woman with 2 months of epigastric pain. A distal pancreatectomy was performed to include the tumor found centered in the splenic vein at the splenic and portal vein confluence and growing into the pancreas in the body on the posterior aspect. A saphenous vein patch was used for reconstruction. PMID- 22051867 TI - Endovascular treatment combined with emboloscleorotherapy for pelvic arteriovenous malformations. AB - PURPOSE: To describe the clinical features and treatment outcomes after combined endovascular and embolosclerotherapy treatment of pelvic arteriovenous malformations (AVMs). METHODS: From November 1996 to May 2011, we treated 12 patients (seven males, five females; mean age, 38.1 +/-14.6 years; age range, 23 70 years) with pelvic AVMs. Our treatment strategy was coil embolization of a dilated draining vein of the AVM to reduce blood flow velocity in the AVM lesion and sclerotherapy of the residual arteriovenous fistulae with high-concentration ethanol to eradicate potential AVM recurrence. To ensure effective endovascular treatment, we used transarterial, transvenous, percutaneous, or combined access routes. Treatment outcomes were assessed with periodic computed tomography angiograms and clinical examinations. RESULTS: During the follow-up period (mean, 33.2 months; median, 21.3 months; range, 1-96 months) after embolosclerotherapy, we observed complete remission (no residual or recurrent AVM lesion on follow-up computed tomography and complete symptomatic relief) in 10 (83.3%) patients and partial remission in two (16.7%) patients. One major complication of focal bladder necrosis occurred (1/22 sessions, 4.5%, 1/12 patients, 8.3%), but this resolved with conservative treatment. As early procedure-related complications, transient pulmonary hypertension and/or hemoglobinuria developed in 54.5% (12/22 sessions) and 22.7% (5/22 sessions) of patients, respectively. CONCLUSIONS: Combined embolosclerotherapy of pelvic AVMs with coils and ethanol was efficacious at achieving complete remission. PMID- 22051868 TI - The feasibility of endovascular aortic repair strategy in treating infected aortic aneurysms. AB - BACKGROUND: Open surgical treatment for an infected aortic aneurysm has a high rate of surgical morbidity and mortality and does not guarantee eradication of the infected nidus. The use of endovascular aortic repair (EVAR) might simplify the procedure and provide a good alternative for this critical condition, but this remains to be proved. This study assessed the efficacy and outcome of EVAR with an adjunctive antibiotic treatment strategy. METHODS: We focused on the experiences and results of the management of infected aortic aneurysms with positive blood cultures. We drew the blood for culture study, immediately prescribed broad-spectrum antibiotics, performed EVAR procedures, and followed this with sensitive antibiotics and adjunctive procedures. RESULTS: Twelve consecutive patients (mean age, 70 years) were included in this EVAR strategy. Three patients had thoracic, two thoracoabdominal, and the remaining seven had infected abdominal aneurysms. Ten Salmonella, one Staphylococcus, and one Streptococcus spp were identified. There was no hospital death. Three patients underwent computed tomography (CT)-guided drainage, and one underwent open laparotomy debridement. Mean follow-up was 24 months. One late death occurred but was unrelated to reinfection. All patients seemed well, with no evidence of EVAR graft infection at a mean follow-up of 23.6 months. CONCLUSIONS: This small multi institutional study summarizing the experiences of patients with an infected aortic aneurysm managed by EVAR and an aggressive antibiotic strategy revealed that this EVAR strategy might be a suitable approach to treating this disease. These favorable results may be typical for Salmonella infection, which was present in most of the patients. Further experience is needed to assess whether this therapeutic strategy works equally well in aneurysm infection caused by other organisms. PMID- 22051869 TI - Long-term incidence of myocardial infarct, stroke, and mortality in patients operated on for abdominal aortic aneurysms. AB - OBJECTIVE: The risks of myocardial infarction (MI) and stroke after abdominal aortic aneurysm (AAA) resection are not known. Prophylaxis with aspirin and statins is not generally recommended, although patients with AAAs have an increased prevalence of cardiovascular atherosclerosis. We report the incidences of MI, stroke, and death in an unselected national cohort of patients operated on for AAAs, with the general population as the control group. METHODS: In a matched cohort study, 11,094 Danish patients who underwent acute or elective open AAA repair from January 1986 through June 2009 were compared with four randomly chosen age- and sex-matched individuals (controls) from the general population (n = 44,364). Data were collected retrospectively from the Danish Vascular Registry (Karbase), the National Population Registry, and the National Inpatient Registry. The groups were analyzed for the incidences of MI, stroke, and death, with up to 20 years of follow-up. RESULTS: AAA patients had an annual MI incidence of 2.5% (hazard ratio, 2.1; 95% confidence interval [CI], 1.9-2.2) compared with the general population. The annual incidence of stroke was 2.9% (hazard ratio, 1.8; 95% CI, 1.6-1.9), and there was a 2.4-fold (95% CI, 2.3-2.4) increase in the hazard of all-cause mortality compared with the general population. CONCLUSION: AAA patients of both sexes have a high risk of atherosclerotic events (MI, stroke) and death, so lifelong prophylaxis must be considered from our epidemiologic data. Randomized trials investigating the potential benefit of aspirin and statin therapy in AAA patients are needed. PMID- 22051871 TI - Characterization of resident surgeon participation during carotid endarterectomy and impact on perioperative outcomes. AB - INTRODUCTION: The impact of resident surgeon participation during vascular procedures on postoperative outcomes is incompletely understood. We characterized resident physician participation during carotid endarterectomy (CEA) procedures within the 2005-2009 American College of Surgeons National Surgical Quality Improvement Participant Use Datafile and evaluated associations with procedural characteristics and perioperative adverse events. METHODS: CEAs were identified using primary current procedural terminology codes; those performed simultaneously with other major procedures or unknown resident participation status were excluded. Group-wise comparisons based on resident participation status were performed using chi(2) or Fisher's exact test for categorical variables and t tests or nonparametric methods for continuous variables. Associations with perioperative adverse events (major = stroke, death, myocardial infarction, or cardiac arrest; minor = peripheral nerve injury, bleeding requiring transfusion, surgical site infection, or wound disruption) were assessed using multivariable logistic regression models adjusting for other known risk factors. RESULTS: A total of 25,280 CEA procedures were analyzed, of which residents participated in 13,705 (54.2%), while residents were absent in 11,575 (45.8%). Among CEAs with resident physician participation, resident level was categorized as junior (postgraduate year [PGY] 1-2) in 21.9%, senior (PGY 3-5) in 52.7%, and fellow (PGY >=6) in 25.3%. Major adverse event rates with and without resident participation were 1.9% versus 2.1%, and minor adverse event rates with and without resident participation were 0.9% versus 1.0%, respectively. In multivariable models, resident physician participation was not associated with perioperative risk for major adverse events (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.75-1.08) or minor adverse events (OR, 0.93; 95% CI, 0.72-1.21). CONCLUSIONS: Resident surgeon participation during CEA is not associated with risk of adverse perioperative events. PMID- 22051872 TI - Pharmacokinetic analysis after implantation of everolimus-eluting self-expanding stents in the peripheral vasculature. AB - BACKGROUND: A novel self-expanding drug-eluting stent was designed to release everolimus 225 MUg/cm(2) to prevent restenosis following peripheral arterial intervention. The purpose of this study was to measure the pharmacokinetic profile of everolimus following stent implantation. METHODS: One hundred four patients with symptomatic peripheral arterial disease underwent implantation of everolimus-eluting stents in the femoropopliteal arteries. In a prespecified subset of 26 patients, blood samples for assay of everolimus content were collected prior to stent implantation, at 1, 4, and 8 hours postprocedure, prior to discharge, and at 1 month postprocedure. RESULTS: A total of 39 stents, ranging from 28 mm to 100 mm in length, were implanted in 26 patients, resulting in a total delivered everolimus dose range of 3.0 to 7.6 mg. Following the procedure, the maximum observed everolimus blood concentrations (C(max)) varied from 1.83 +/- 0.05 ng/mL after implantation of a single 80-mm stent to 4.66 +/- 1.78 ng/mL after implantation of two 100-mm stents. The mean time to peak concentration (T(max)) varied from 6.8 hours to 35 hours. The pharmacokinetics of everolimus were dose-proportional in that dose-normalized C(max) and area under the curve values were constant over the studied dose range. CONCLUSIONS: After implantation of everolimus-eluting self-expanding stents in the femoropopliteal arteries, systemic blood concentrations of everolimus are predictable and considerably lower than blood concentrations observed following safe oral administration of everolimus. PMID- 22051873 TI - Polydeoxyribonucleotide restores blood flow in an experimental model of ischemic skin flaps. AB - BACKGROUND: Ischemia is a major factor contributing to failure of skin flap surgery, which is routinely used for coverage of wounds to prevent infection and to restore form and function. An emerging concept is that adenosine A(2A) receptors can improve tissue oxygenation by stimulating angiogenesis, likely through vascular endothelial growth factor (VEGF). This study assessed the ability of polydeoxyribonucleotide (PDRN) to restore blood flow and improve wound healing, acting through the A(2A) receptor, in a rat model of ischemic skin flaps. METHODS: The H-shaped double-flap model was used in male Sprague-Dawley rats. After surgical procedures, the animals were randomized to receive intraperitoneal PDRN (8 mg/kg) or vehicle (NaCl 0.9%). Rats were euthanized 3, 5, and 10 days after skin injury, after the evaluation of skin perfusion by laser Doppler. The wounds underwent histologic analysis and were measured for VEGF messenger RNA and protein expression, hypoxia inducible factor-1-alpha (HIF 1alpha), and inducible nitric oxide synthase (iNOS) protein expression, and nitrite content. RESULTS: Blood flow markedly increased in blood flow in ischemic flaps treated with PDRN, with a complete recovery starting from day 5 (ischemic flap + vehicle, 1.80 +/- 0.25; ischemic flap + PDRN, 2.46 +/- 0.25; P < .001). Administration of PDRN enhanced the expression of VEGF (ischemic flap + vehicle, 5.3 +/- 0.6; ischemic flap + PDRN, 6.2 +/- 0.5; P < .01) at day 5, and iNOS (ischemic flap + vehicle, 3.9 +/- 0.6; ischemic flap + PDRN, 5.3 +/- 1; P < .01), but reduced HIF-1alpha expression (ischemic flap + vehicle, 7 +/- 1.1; ischemic flap + PDRN, 4.8 +/- 0.5; P < .05) at day 3. Histologically, the PDRN-treated group showed complete re-epithelialization and well-formed granulation tissue rich in fibroblasts. CONCLUSIONS: These results suggest that PDRN restores blood flow and tissue architecture, probably by modulating HIF-1alpha and VEGF expression, and may be an effective therapeutic approach in improving healing of ischemic skin flaps. PMID- 22051874 TI - Heart failure is associated with reduced patency after endovascular intervention for symptomatic peripheral arterial disease. AB - OBJECTIVE: Congestive heart failure (CHF) is a highly prevalent comorbidity among patients with symptomatic peripheral arterial disease. The effect of CHF on the procedural success of endovascular treatment, however, remains unknown. Theoretically, poor inflow secondary to systolic dysfunction and peripheral vascular alterations may predispose endovascular interventions to failure. METHODS: A retrospective review of a prospectively maintained database was performed to identify CHF patients undergoing endovascular peripheral arterial intervention from 2004 to 2009. Demographics, comorbidities, procedural details, and outcomes were analyzed. Patients underwent duplex ultrasound imaging and clinical follow-up at scheduled intervals. Kaplan-Meier and Cox proportional hazards models were used to evaluate risk factors for loss of primary patency, secondary patency, and limb salvage. RESULTS: Of 1220 patients undergoing intervention, 271 (22%) with documented congestive heart failure (CHF) underwent an intervention for claudication (22.5%) or critical limb ischemia (77.5%). Primary patency at 1 year was 51.9% +/- 2.5% among those with CHF vs 64.6% +/- 1.3% in those without CHF (P < .001); this disparity continued throughout follow up (P < .001). Patients with CHF also had reduced secondary patency throughout follow-up. Multivariate analysis showed CHF was an independent predictor of reduced primary patency (hazard ratio [HR], 1.2; 95% confidence interval [CI] 1.0 1.4; P = .038) and secondary patency (HR, 1.5; 95% CI, 1.2-1.8; P < .001). In the setting of CHF, 1-year patency was 56.6% +/- 4.1% if the ejection fraction (EF) was >40% (n = 147) vs 43.2% +/- 3.5% if the EF was <40% (n = 124; P < .001). Secondary patency was also significantly reduced in patients with EF <40% throughout follow-up compared with patients without CHF (n = 949) as well as those with CHF and EF >40% (P < .001). CHF with EF <40% was an independent predictor of reduced primary patency (HR, 1.4; 95% CI, 1.2-1.8; P < .01) and secondary patency (HR, 1.8; 95% CI, 1.3-2.3; P < .001). Limb salvage was also worse in patients with EF <40% (P = .038). CONCLUSIONS: CHF is associated with reduced patency after peripheral endovascular intervention and is an independent risk factor for patency loss. Specifically, CHF and reduced EF (<40%) is a strong independent risk factor for patency loss. PMID- 22051875 TI - Long-term results of direct and indirect endovascular revascularization based on the angiosome concept in patients with critical limb ischemia presenting with isolated below-the-knee lesions. AB - OBJECTIVE: We compared clinical outcomes between limbs with and without achievement of feeding artery flow by endovascular therapy (EVT) based on the angiosome concept in critical limb ischemia (CLI) patients with isolated below the-knee (BTK) lesions and assessed factors influencing major amputation (MA). METHOD: We analyzed 369 limbs from 329 consecutive patients (224 men; age, 70 +/- 11 years) with ischemic ulceration or gangrene, or both, presenting with isolated BTK lesions (Rutherford class 5, 270 limbs; class 6, 99 limbs) with a pretreatment ankle-brachial index of 0.79 +/- 0.26. Patients underwent successful EVT, without bypass surgery. Limbs were classified into direct (n = 200) and indirect (n = 169) groups by whether feeding artery flow to the site of ulceration or gangrene was successfully achieved, based on the angiosome concept. Unadjusted and adjusted (by propensity score matching) between-group rates of amputation-free survival (AFS) and freedom from major amputation (MA) and major adverse limb event (MALE) were compared by Kaplan-Meier analysis and the log-rank test. The independent determinants of MA in the direct and indirect groups were explored by multivariable analysis. RESULTS: During follow-up (mean, 18 +/- 16 months), the overall limb salvage rate was 81% (300 of 369), death occurred in 36% (119 of 329), and the reintervention rate was 31% (114 of 369). After propensity score adjustment, the estimated (+/- standard error) rates for AFS (49% +/- 8% vs 29% +/- 6%; P = .0002), freedom from MALE (51% +/- 8% vs 28% +/- 8%, P = .008), and major amputation (82% +/- 5% vs 68% +/- 5%, P = .01) were significantly higher in the direct group than in the indirect group for up to 4 years after the index procedure. After multivariable Cox proportional analysis, the independent factors associated with major amputation were hemoglobin A(1c) level (hazard ratio [HR], 1.4; 95% confidential interval [CI], 1.1-1.9; P = .006) and cilostazol administration (HR, 0.28; 95% CI, 0.11-0.70; P = .006) in the direct group, and C-reactive protein level (HR, 1.2; 95% CI, 1.1-1.4; P = .002) in the indirect group. CONCLUSION: Achieving direct flow by angioplasty based on the angiosome concept in CLI patients with isolated BTK lesions is clinically important for AFS and freedom from MA and MALE. Limb salvage factors appear to differ between patients with and without direct flow from the feeding artery after EVT. PMID- 22051876 TI - Quality of life in chronic venous disease patients measured by short Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) in Serbia. AB - BACKGROUND: This was a psychometric validation of the short Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) as quality of life (QOL) instrument for chronic venous disease (CVD) patients. METHODS: Patients aged >18 years who had CVD in CEAP C stages C0s to C6 were included in the study. Diagnosis was made by general practitioners according to CVD symptoms and visual examination of the lower extremities. QOL was assessed with the self administrated CIVIQ-14. The reliability, construct, and convergent validity of the CIVIQ-14 was estimated as well as QOL of CVD patients according to CEAP C stages. RESULTS: The study comprised 2260 subjects who fully completed the CIVIQ 14. CIVIQ-14 had a high level of reliability, construct, and convergent validity, but the structure of its three dimensions (pain [P], physical [PHY], and psychological [PSY]) was suboptimal. After adjustment for age, body mass index, and number of CVD symptoms, CIVIQ -14 global, P, PHY, and PSY scores showed significant progressive reduction of QOL from CEAP class C0s to C6. These differences were present in both sexes. The progressive impairment of the QOL involved primarily the pain and the physical items. For all CEAP C classes, the P and PHY scores were lower than the PSY scores. Global scores for men and women were: 76.7 and 73.9 for C0s; 75.5 and 70.6 for C1; 67.8 and 64.5 for C2; 68.3 and 61.6 for C3; 60.7 and 54.6 for C4; 49.5 and 50.2 for C5; and 41.3 and 46.7 for C6. CONCLUSIONS: CVD in the lower extremities has a substantial effect on both physical and psychologic aspects of QOL, the physical aspects of QOL (P and PHY items) being more important. CIVIQ-14 is valuable in assessing QOL in CVD patients. Further investigations are necessary to confirm the stability of its two dimensions. PMID- 22051877 TI - Left renocaval venous bypass with autologous great saphenous vein for nutcracker syndrome. AB - Nutcracker syndrome results from left renal vein compression by the abdominal aorta and the superior mesenteric artery. The consecutively increased renal venous pressure results in hematuria, proteinuria, flank pain, left-sided varicocele, pelvic congestion, and others. We report a 25-year-old man with nutcracker syndrome who underwent successful left renocaval venous bypass with autologous great saphenous vein. The patient's condition clearly improved, with no clinical relapse after treatment. Ultrasound imaging showed patency of the venous bypass and decreased venous hypertension. This technique is a feasible choice for surgical treatment of nutcracker syndrome, with a low incidence of complications and satisfactory results. PMID- 22051879 TI - Expression of midkine and vascular endothelial growth factor in gastric cancer and the association of high levels with poor prognosis and survival. AB - The aim of the present study was to investigate the expression of midkine (MK) and vascular endothelial growth factor (VEGF) in gastric cancer and its relationship with gastric cancer prognosis and survival rate. We recruited 107 patients with complete clinical data and available tissue samples [gastric cancer tissue (n=107); adjacent normal gastric mucosa (n=31)]. MK and VEGF expression in these tissues were assayed by immunohistochemistry. The association of MK or VEGF expression with various prognostic factors in gastric cancer and the 5-year survival of gastric cancer patients were analyzed. MK and VEGF immunoreactivity were detected in 69.2% (74 out of 107 cases) and 66.4% (71 out of 107 cases) of gastric cancer tissues, but not in normal gastric tissues (P=0.00). MK and VEGF expression was correlated with tumor size, depth of invasion, lymph node metastasis and pathological stage (P<0.01), but not with age and gender (P>0.05). MK expression was positively correlated with VEGF expression (r=0.681, P<0.01). In addition, MK or VEGF expression was negatively correlated with the 5-year survival rate (P<0.01). The 5-year survival rate was significantly higher in patients with MK- or VEGF-immunonegative tumors than in patients with immunopositive ones (P<0.01). Co-expression of MK and VEGF was an independent predictor of gastric cancer prognosis. Expression of MK and VEGF is increased in gastric cancer and increased expression is closely correlated with poor prognosis and survival. PMID- 22051878 TI - Neuropilins are positive regulators of Hedgehog signal transduction. AB - The Hedgehog (Hh) pathway is essential for vertebrate embryogenesis, and excessive Hh target gene activation can cause cancer in humans. Here we show that Neuropilin 1 (Nrp1) and Nrp2, transmembrane proteins with roles in axon guidance and vascular endothelial growth factor (VEGF) signaling, are important positive regulators of Hh signal transduction. Nrps are expressed at times and locations of active Hh signal transduction during mouse development. Using cell lines lacking key Hh pathway components, we show that Nrps mediate Hh transduction between activated Smoothened (Smo) protein and the negative regulator Suppressor of Fused (SuFu). Nrp1 transcription is induced by Hh signaling, and Nrp1 overexpression increases maximal Hh target gene activation, indicating the existence of a positive feedback circuit. The regulation of Hh signal transduction by Nrps is conserved between mammals and bony fish, as we show that morpholinos targeting the Nrp zebrafish ortholog nrp1a produce a specific and highly penetrant Hh pathway loss-of-function phenotype. These findings enhance our knowledge of Hh pathway regulation and provide evidence for a conserved nexus between Nrps and this important developmental signaling system. PMID- 22051880 TI - Oxygen bridged neutral annulenes: a novel class of materials for organic field effect transistors. AB - New, neutral, meso-substituted tetraoxa[22]annulene[2,1,2,1] aromatic macrocycles are synthesised and disclosed as new p-type semiconductors with reproducible bulk like carrier mobility (as high as 0.40 cm(2) V(-1) s(-1)) on highly crystalline thin films deposited on octadecyltrichlorosilane modified SiO(2). PMID- 22051882 TI - Protective effect of hexane extracts of Uncaria sinensis against photothrombotic ischemic injury in mice. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria sinensis (US) has been used in traditional Korean medicine to treat vascular disease and to relieve various neurological symptoms. AIM OF THE STUDY: Scientific evidence related to the effectiveness or action mechanism of US on cerebrovascular disease has not been examined experimentally. Here, we investigated the cerebrovascular protective effect of US extracts on photothrombotic ischemic injury in mice. MATERIALS AND METHODS: US hexane extracts (HEUS), ethyl acetate extracts (EAEUS) and methanol extracts (MEUS) were administered intraperitoneally 30 min before ischemic insults. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, neurological score and the activation of Akt and eNOS in ischemic brain. RESULTS: HEUS more significantly reduced infarct volume and edema than did EAEUS and MEUS following photothrombotic cortical occlusion. HEUS produced decreased infarct volume and edema size, and improved neurological function in a concentration-dependent manner (10, 50, and 100 mg/kg). However, HEUS did not reduce brain infarction in eNOS KO mice, suggesting that the protective effect of HEUS is primarily endothelium-dependent. Furthermore, HEUS (10-300 MUg/ml) produced a concentration-dependent relaxation in mouse aorta and rat basilar artery, which was not seen in eNOS KO mouse aorta, suggesting that HEUS cause vasodilation via an eNOS-dependent mechanism. This correlated with increased phosphorylation of Akt and eNOS in the brains of HEUS treated mice. CONCLUSION: HEUS prevent cerebral ischemic damage by regulating Akt/eNOS signaling. US, herbal medicine, may be the basis of a novel strategy for the therapy of stroke. PMID- 22051883 TI - Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates. AB - Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying protein aggregation diseases. Here we report the chemical design of a library of anionic luminescent conjugated oligothiophenes (LCOs), which can be utilized as ligands for detection of protein aggregates. Certain molecular requirements were shown to be necessary for detecting (i) early non-thioflavinophilic protein assemblies of Abeta1-42 and insulin preceding the formation of amyloid fibrils and (ii) for obtaining distinct spectral signatures of the two main pathological hallmarks observed in human Alzheimer's diease brain tissue (Abeta plaques and neurofibrillary tangles). Our findings suggest that a superior anionic LCO-based ligand should have a backbone consisting of five to seven thiophene units and carboxyl groups extending the conjugated thiophene backbone. Such LCOs will be highly useful for studying the underlying molecular events of protein aggregation diseases and could also be utilized for the development of novel diagnostic tools for these diseases. PMID- 22051885 TI - Correlation of the Taq1 dopamine D2 receptor gene and percent body fat in obese and screened control subjects: a preliminary report. AB - While there is a considerable body of literature correlating the role of dopaminergic genes and obesity, body mass index, body type, overeating, carbohydrate binging, energy expenditure and low dopamine D2 receptor (D2R) receptor density, there is a paucity of research concerning the dopamine D2 receptor gene (DRD2) variants and percent body fat. We report here the potential association of DRD2 genotypes and the percent fat phenotype. In this study we genotyped 122 obese/overweight (O/OW) Caucasian subjects and 30 non-obese Caucasian controls, screened to exclude substance abuse. The subjects were assessed for weight, body mass index (BMI; kg m(-2)) and percent body fat using dual energy X-ray absorptiometry (DEXA). The sample was separated into two independent groups; those with the Taq1 A1 allele (A1/A1 or A1/A2) and those without the A1 allele (A2/A2). The controls had a normal range of body fat (25 31% for females and 18-25% for males). The O/OW subjects had a percent body fat value of over 32% for females and over 25% for males. For the O/OW subjects, the mean BMI was 29.3 +/- 6.25 kg m(-2), mean body fat was 42.1 +/- 7.5% and mean weight was 82.7 +/- 21.7 kg. The DRD2 Taq1 A1 allele was present in 67% of the O/OW subjects compared to 3.3% of super controls (A group), 33.3% of screened (for drug abuse and obesity) controls (B group) and unscreened literature controls 29.4% (P<= 0.001). Comparing all cases with more than 34% body fat, utilizing logistic regression analysis, the DRD2 A1 allele accounts for 45.9% of the variance, which is statistically significant (chi(2) = 43.47, degrees of freedom (df) = 1, P < 0.0001). These results are consistent with a role for the DRD2 gene in obesity, as measured by percent body fat as well as by weight and BMI. PMID- 22051884 TI - Role of PDE3A in regulation of cell cycle progression in mouse vascular smooth muscle cells and oocytes: implications in cardiovascular diseases and infertility. AB - Phosphodiesterase-3 (PDE3) is a major cAMP-hydrolyzing PDE in vascular smooth muscle cells (VSMCs) and oocytes. The exact role and contribution of the two PDE3 isoforms, PDE3A and PDE3B, in VSMC growth regulation and oocyte maturation was examined using PDE3A (3A) and PDE3B (3B) knockout (KO) mouse models. PDE3A deficient VSMCs exhibit marked reduction in mitogen-induced cell growth due to cell cycle arrest at G0-G1 phase, which resulted from dysregulation of cAMP/protein kinase A (PKA)-activated and mitogen-activated protein kinase (MAPK) signaling pathways, as well as from alterations in key cell cycle regulatory proteins. Similarly, PDE3A-deficient oocytes exhibit cell cycle arrest at G2/M phase because increased cAMP/PKA signaling in KO oocytes most likely inhibits Cdc25B-catalyzed dephosphorylation/activation of Cdc2 (maturation promoting factor (MPF)), a key regulator of G2/M transition. PMID- 22051886 TI - N-glucosyltransferase UGT76C2 is involved in cytokinin homeostasis and cytokinin response in Arabidopsis thaliana. AB - Cytokinins are a class of phytohormones that play a crucial role in plant growth and development. The gene UGT76C2 encoding cytokinin N-glucosyltransferase of Arabidopsis thaliana has been previously identified. To determine the in planta role of UGT76C2 in cytokinin metabolism and response, we analyzed the phenotypes of its loss-of-function mutant (ugt76c2) and its overexpressors. The accumulation level of the cytokinin N-glucosides was significantly decreased in ugt76c2, but substantially increased in UGT76C2 overexpressors compared with the wild type. When treated with exogenously applied cytokinin, ugt76c2 showed more sensitivity and UGT76C2 overexpressors showed less sensitivity to cytokinin in primary root elongation, lateral root formation, Chl retention and anthocyanin accumulation. Under normal growth conditions ugt76c2 had smaller seeds than the wild type, with accompanying lowered levels of active and N-glucosylated cytokinin forms. The expression levels of cytokinin-related genes such as AHK2, AHK3, ARR1, IPT5 and CKX3 were changed in ugt76c2, suggesting homeostatic control of cytokinin activity. Studies of spatiotemporal expression patterns showed that UGT76C2 was expressed at a relatively higher level in the seedling and developing seed. In their entirety, our data, based mainly on this comparison and opposite phenotypes of knockout and overexpressors, strongly suggest that UGT76C2 is involved in cytokinin homeostasis and cytokinin response in planta through cytokinin N glucosylation. PMID- 22051887 TI - Clinicopathologic features and risk factors for extrahepatic recurrences of hepatocellular carcinoma after curative resection. AB - BACKGROUND: The aim of this study was to clarify the clinicopathologic features of hepatocellular carcinoma (HCC) patients with extrahepatic metastasis after the removal of primary HCC, and the risk factors of extrahepatic recurrence. METHODS: Clinicopathologic data were available for 264 HCC patients who underwent an R0 resection for HCC. Twenty-six patients who developed extrahepatic recurrence during the follow-up period (EXT group) were compared with patients who remained free from recurrence for at least 5 years after resection (n = 46) (No R group) or had only intrahepatic recurrences (n = 193) (INT group). We also estimated the risk factors of extrahepatic recurrence and survival in these 26 patients. RESULTS: There were significant differences in primary tumor size, patient's age, findings in the noncancerous portion, macroscopic type, ductal invasion, intrahepatic metastasis, hepatic involvement and curability of primary tumor, treatment for recurrent tumor, and prognosis between the EXT group and the other groups. Extrahepatic recurrence was significantly associated with six factors by univariate analyses: age, indocyanine green (ICG) 15-min retention rate, tumor size, hepatic involvement of primary tumor, type of hepatectomy, and TNM stage, of which tumor size was an independent risk factor. Resection of recurrent tumor was the only independent favorable factor for survival of patients with extrahepatic recurrence. CONCLUSIONS: HCC patients with extrahepatic recurrence had advanced primary tumors and poor prognosis. HCC patients with primary tumors larger than 60 mm were predicted to develop extrahepatic recurrence. Resection of recurrent tumor can improve the prognosis of HCC patients with extrahepatic recurrence. PMID- 22051888 TI - Total ischemia time alters the longitudinal and circumferential shortening of the right ventricle in transplanted hearts. AB - OBJECTIVES: Ischemia time is a risk factor for mortality and right ventricular (RV) failure after heart transplantation. The purpose of this study was to determine the effect of ischemia time on known transesophageal echocardiography (TEE) parameters of RV function and on a novel quantitative measurement of RV circumferential shortening. METHODS: Right and left ventricular (LV) function was evaluated retrospectively in 20 consecutive patients after heart transplant using known TEE parameters as well as a quantitative measurement of circumferential contraction. The control group consisted of 20 patients undergoing coronary artery bypass grafting (CABG) with no documented RV dysfunction. RESULTS: Posttransplant TEE parameters of RV function were depressed compared with post cardiopulmonary bypass CABG patients. Significant correlation was observed between tricuspid annular planar systolic excursion, basal, mid, and global circumferential shortening and total ischemia time. CONCLUSION: Total ischemia time of the transplanted heart may play a role in deterioration of longitudinal and circumferential shortening of the RV. PMID- 22051889 TI - Inflammation: Under the skin. PMID- 22051890 TI - Vaccines for the twenty-first century society. AB - Vaccines have been one of the major revolutions in the history of mankind and, during the twentieth century, they eliminated most of the childhood diseases that used to cause millions of deaths. In the twenty-first century, vaccines will also play a major part in safeguarding people's health. Supported by the innovations derived from new technologies, vaccines will address the new needs of a twenty first century society characterized by increased life expectancy, emerging infections and poverty in low-income countries. PMID- 22051891 TI - Infectious disease: a ray of sunshine for TB treatment. PMID- 22051892 TI - Versatile trifunctional chemosensor of rhodamine derivative for Zn2+, Cu2+ and His/Cys in aqueous solution and living cells. AB - On the basis of rhodamine, a versatile trifunctional chemosensor RP has been synthesized. It can selectively and sensitively recognize Cu(2+) and Zn(2+) in different solutions. Based on the zinc-containing [RP@Zn(2+)] complex, it shows highly selective recognition for His/Cys. Fluorescent imaging of Zn(2+) in living cells was also obtained. PMID- 22051894 TI - Paying for Quality: Understanding and Assessing Physician Pay-for-Performance Initiatives. AB - Pay-for-performance (P4P) initiatives have been discussed since the early 1990s, but support for the concept has grown recently, fueled by experience with quality of care measures, endorsements by key players and research that underlines the need for quality improvements and reform to the physician payment system. This synthesis examines the evidence on P4P. Key findings include: About one-third of U.S. physicians already face quality-based incentives under their managed care contracts. These measures most often relate to clinical targets, efficiency, patient satisfaction and use of information technology, but apply to a limited set of specific diseases and preventive care services. While 80 percent of plans pay for meeting benchmarks, 20 percent pay for improvements in performance. Overall, incentive payments are small, averaging at most 5 percent of total payments. While large-scale, ""real-life"" research consistently shows improvement in quality indicators when P4P is in place, it is hard to disentangle the impact of P4P from that of other simultaneous quality initiatives. Evidence of P4P impact from small controlled studies has not been positive. Doctors are generally supportive of P4P but concerned about how well it can be implemented. PMID- 22051895 TI - Investigation on the dynamics of electron transport and recombination in TiO2 nanotube/nanoparticle composite electrodes for dye-sensitized solar cells. AB - In this work, we report on fabrication and characterization of dye-sensitized solar cells based on TiO(2) nanotube/nanoparticle (NT/NP) composite electrodes. TiO(2) nanotubes were prepared by anodization of Ti foil in an organic electrolyte. The nanotubes were chemically separated from the foil, ground and added to a TiO(2) nanoparticle paste, from which composite NT/NP electrodes were fabricated. In the composite TiO(2) films the nanotubes existed in bundles with a length of a few micrometres. By optimizing the amount of NT in the paste, dye sensitized solar cells with an efficiency of 5.6% were obtained, a 10% improvement in comparison to solar cells with pure NP electrodes. By increasing the fraction of NT in the electrode the current density increased by 20% (from 11.1 to 13.3 mA cm(-2)), but the open circuit voltage decreased from 0.78 to 0.73 V. Electron transport, lifetime and extraction studies were performed to investigate this behavior. A higher fraction of NT in the paste led to more and deeper traps in the resulting composite electrodes. Nevertheless, faster electron transport under short-circuit conditions was found with increased NT content, but the electron lifetime was not improved. The electron diffusion length calculated for short-circuit conditions was increased 3-fold in composite electrodes with an optimized NT fraction. The charge collection efficiency was more than 90% over a wide range of light intensities, leading to improved solar cell performance. PMID- 22051893 TI - Effects of spatial attention on motion discrimination are greater in the left than right visual field. AB - In order to investigate differences in the effects of spatial attention between the left visual field (LVF) and the right visual field (RVF), we employed a full/poor attention paradigm using stimuli presented in the LVF vs. RVF. In addition, to investigate differences in the effects of spatial attention between the dorsal and ventral processing streams, we obtained motion thresholds (motion coherence thresholds and fine direction discrimination thresholds) and orientation thresholds, respectively. The results of this study showed negligible effects of attention on the orientation task, in either the LVF or RVF. In contrast, for both motion tasks, there was a significant effect of attention in the LVF, but not in the RVF. These data provide psychophysical evidence for greater effects of spatial attention in the LVF/right hemisphere, specifically, for motion processing in the dorsal stream. PMID- 22051896 TI - Body mass index and injury severity in adolescent males. AB - Childhood obesity's relationship to injury severity has not been determined. This study examined the relationship between obesity and injury severity, differences in injury severity between weight groups, and injury predictors. The sample included 611 adolescent males treated for injury at a 10-day camping event in Virginia. Findings indicate a significant relationship between body mass index percentile and injury severity (r = .08, p = .04) and less injury severity in normal-weight adolescents, F(2, 608) = 5.27, p < .01. Predictors of injury severity were cause, place injury occurred and injury type, R(2) change = .07, F(5, 601) = 6.52, p < .01. Implications are that overweight/obese adolescents may have increased risk of serious injuries. Examining predictors may decrease incidence of injuries at future events. PMID- 22051899 TI - Intermedin and the unfolded protein response. PMID- 22051897 TI - Beneficial effects of Acer okamotoanum sap on L-NAME-induced hypertension-like symptoms in a rat model. AB - The sap of Acer okamotoanum has been termed 'bone-benefit-water' in Korea owing to its mineral and sugar content. In particular, the calcium (Ca) and potassium (K) concentrations of the sap of Acer okamotoanum are 40- and 20-times higher, respectively, than commercial spring water. In the present study, we examined whether Acer okamotoanum sap improves or prevents hypertension-like symptoms in a rat model. Male Sprague-Dawley rats (8-weeks-old) were provided commercial spring water supplemented with 25, 50 or 100% Acer okamotoanum sap, 3% potassium ions (K+) or captopril, and treated daily for 2 weeks with NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg/day) by subcutaneous injection, in order to induce hypertensive symptoms. Rats were euthanized 6 h following the final injection. To assess the effect of the sap on hypertension-like symptoms, we examined the mean blood pressure (BP), protein levels and localization of endothelial nitric oxide synthase (eNOS) in the descending aorta of the rats. BP levels were significantly lower in hypertensive rats received 25, 50 and 100% sap compared with rats who were administered only commercial spring water. Protein levels of eNOS were repressed in L-NAME-only-treated rats, but were elevated in the descending aorta of rats administered captopril, K+ water and Acer okamotoanum sap (25, 50 and 100%) up to the level of the sham group provided commercial spring water, and then injected with dimethyl sulfoxide for the same period of time. Localized eNOS protein was abundantly expressed in the perivascular descending aorta adipose tissue of the rats. Taken together, these results demonstrated that the sap of Acer okamotoanum ameliorated high BP induced by L-NAME treatment in a rat model. PMID- 22051898 TI - Impact of central hypovolemia on photoplethysmographic waveform parameters in healthy volunteers. Part 1: time domain analysis. AB - INTRODUCTION: Our study sought to explore changes in photoplethysmographic (PPG) waveform param- eters, during lower body negative pressure (LBNP) which simulated hypovolemia, in spontaneously breathing volunteers. We hypothesize that during progressive LBNP; there will be a preservation of ear PPG parameters and a decrease in finger PPG parameters. METHODS: With IRB approval, 11 volunteers underwent a LBNP protocol at baseline, 30, 75, and 90 mm Hg (or until the subject became symptomatic). Subjects were monitored with finger and ear pulse oximeter probes, an ECG, and a finger arterial blood pressure monitor. The square root of the mean of the squared differences between adjacent NN intervals (RMSSD) which is the time domain analysis of the heart rate variability (HRV) was measured. PPG waveforms were analyzed for height, area, width 50, maximum and minimum slope. Data are presented as median and inter-quartile range. Friedman ANOVA and Wilcoxon tests were used to identify changes in hemo- dynamic and PPG parameters, P < 0.017 was considered statistically significant. RESULTS: There were no significant changes in the blood pressure variables at LBNP(30), but at and beyond LBNP(75), the decreases in systolic, mean and pulse pressure were significant as was the increase in diastolic pressure. Heart rate increased significantly at LBNP(30), reaching a maximum of 75.4% above baseline at the symptomatic phase while RMSSD showed significant reduction at LBNP(75). Finger PPG height, area, width 50, and maximum slope decreased significantly at LBNP(30) and during symptomatic phase they showed a reduction of 59.4, 76.9, 27.4 and 51.6%, respectively. Ear PPG height, area, width 50 and maximum slope did not change significantly until the LBNP(75), reached. During symptomatic phase, the respective declines reached 39.3, 61.0, 21.4 and 34.9%. CONCLUSION: PPG waveform parameters may prove to be sensitive and specific as early indicators of blood loss. These PPG changes were observed before profound decreases in arterial blood pressure. The relative sparing of central cutaneous blood flow is consistent with the increased parasympathetic innervation of central structures. PMID- 22051903 TI - A guide to out of programme training and experience in Australia. PMID- 22051904 TI - Efficacy and safety of oral deferasirox treatment in the posttransplant period for patients who have undergone allogeneic hematopoietic stem cell transplantation (alloHSCT). AB - Iron overload is considered to be associated with various complications in patients who undergo both allogeneic (allo) and autologous hematopoietic stem cell transplantation (HSCT). A total of 23 alloHSCT recipients who started deferasirox treatment due to hyperferritinemia (ferritin >=1,000 ng/mL) were analyzed retrospectively. The demographic characteristics, data about deferasirox treatment, and history of phlebotomy were obtained from the patients' files. The reduction in posttreatment ferritin levels was found statistically significant compared with pretreatment ferritin levels in both def+phlebotomy and def+nonphlebotomy groups (p = 0.025 and 0.017, respectively). The liver enzymes, especially ALT and bilirubins, were significantly reduced after the treatment (p < 0.05). The deferasirox treatment reduced pretreatment ferritin levels below the level of 1,000 ng/mL in a median period of 94 days, and these data were found to be statistically significant (p < 0.05). The median treatment duration time with deferasirox was 94 days (72-122). The most common adverse effects were nausea and vomiting, which occurred in three of the patients (13%). In conclusion, our data suggest that oral deferasirox treatment may be used as a safe and effective alternative method for reducing iron overload in alloHSCT recipients, whether combined with or without phlebotomy. PMID- 22051905 TI - Minimum effective drug concentrations of a transdermal patch system containing procyclidine and physostigmine for prophylaxis against soman poisoning in rhesus monkeys. AB - A transdermal patch system containing procyclidine, an N-methyl-d-aspartate receptor antagonist possessing anticholinergic action, and physostigmine, a reversible cholinesterase inhibitor, was developed, and its prophylactic efficacy against soman intoxication was investigated. Male rhesus monkeys were shaved on the dorsal area, attached with a matrix-type patch with various sizes (2*2 to 7*7 cm) for 24 or 72 h, and challenged with 2*LD50 doses (13MUg/kg) of soman. The smallest patch size for the protection against lethality induced by soman intoxication was 3*3cm, resulting in blood procyclidine concentration of 10.8 ng/ml, blood physostigmine concentration of 0.54 ng/ml, which are much lower concentrations than maximum sign-free doses, and blood cholinesterase inhibition of 42%. The drug concentrations and enzyme inhibition rate corresponding to a diverging point of survivability were presumably estimated to be around 7 ng/ml for procyclidine, 0.35 ng/ml for physostigmine, and 37% of enzyme inhibition. Separately, in combination with the patch treatment, the post treatment consisting of atropine (0.5 mg/kg) plus 1-[([4 (aminocarbonyl)pyridinio]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium (HI 6, 50 mg/kg) exerted protection against 5*LD50 challenge of soman, which means the posttreatment remarkably augmented the efficacy of the patch. Additionally, it was found that brain injuries induced by soman toxicity were effectively prevented by the patch treatment according to histopathological examinations. These results suggest that the patch system could be an effective alternative for diazepam, an anticonvulsant, and the current pyridostigmine pretreatment, and especially in combination with atropine plus HI-6, could be a choice for quality survival from nerve-agent poisoning. PMID- 22051915 TI - Long-term ocular outcome in congenital toxoplasmosis: a prospective cohort of treated children. AB - OBJECTIVES: Congenital toxoplasmosis remains a public health problem throughout the world. Long-term longitudinal studies are still needed to argument controversial screening and treatment strategies and to enable to accurately counsel parents. METHODS: We conducted a prospective cohort study over 16 years in Marseilles, France. Seronegative pregnant women underwent monthly serological testing. Children were treated antenatally with rovamycine as soon as maternal infection was detected and with pyrimethamine and sulfadoxine in case of positive Toxoplasma PCR on amniotic fluid. Postnatal treatment with pyrimethamine and sulfadoxine was systematically prescribed for one year and possibly continued at the physician discretion. RESULTS: 127 children were included. 24 children (18.9%) presented ocular lesions causing visual impairment in eight cases. Eleven children (8.7%) presented with ocular lesions at birth, mostly macular. Sixteen children (12.6%) developed ocular lesions during follow-up, mostly peripheral. The first ocular lesion could occur as late as 12 years after birth. No significant risk factor of chorioretinitis was identified including gestational age at infection, type of antenatal treatment and shorter postnatal treatment. CONCLUSIONS: These results confirm the overall good prognosis of congenital toxoplasmosis in Europe but highlight though a low risk of late ocular manifestation. Chorioretinitis affected 18.9% of children suffering from congenital toxoplasmosis despite antenatal and neonatal screening associated with early treatment. Long-standing follow-up is needed because first lesion can occur as late as 12 years after birth. Late lesions were less often macular but nevertheless caused sometimes visual impairment. PMID- 22051914 TI - Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a genetically diverse disease. At least 15 ALS-associated gene loci have so far been identified, and the causative gene is known in approximately 30% of familial ALS cases. Less is known about the factors underlying the sporadic form of the disease. The molecular mechanisms of motor neuron degeneration are best understood in the subtype of disease caused by mutations in superoxide dismutase 1, with a current consensus that motor neuron injury is caused by a complex interplay between multiple pathogenic processes. A key recent finding is that mutated TAR DNA-binding protein 43 is a major constituent of the ubiquitinated protein inclusions in ALS, providing a possible link between the genetic mutation and the cellular pathology. New insights have also indicated the importance of dysregulated glial cell-motor neuron crosstalk, and have highlighted the vulnerability of the distal axonal compartment early in the disease course. In addition, recent studies have suggested that disordered RNA processing is likely to represent a major contributing factor to motor neuron disease. Ongoing research on the cellular pathways highlighted in this Review is predicted to open the door to new therapeutic interventions to slow disease progression in ALS. PMID- 22051916 TI - Clinical significance of Staphylococcus aureus bacteriuria in a nationwide study of adults with S. aureus bacteraemia. AB - OBJECTIVES: To evaluate the clinical significance of Staphylococcus aureus bacteriuria (SABU) in adults with S. aureus bacteraemia (SAB). METHODS: All individuals >=18 years old diagnosed with SAB in Iceland between December 1st 2003 and November 30th 2008 were retrospectively identified. Data was collected from medical records. Concomitant SABU was defined as growth of S. aureus in a urine sample taken within 24 h of the index blood culture. RESULTS: SABU was seen in 27 of 166 (16.3%) SAB patients having urine cultured before administration of antibiotics, but after excluding those with SAB of urinary tract origin SABU was seen in 16 of 152 (10.5%). In this latter cohort SABU was independently associated with having endocarditis (RR 6.68; 95% CI 1.53-17.3) and admission to intensive-care unit (RR 2.84; 95% CI 1.25-4.44), while for having complicated SAB the RR was 1.56 (95% CI 0.96-1.80). No correlation was seen with mortality or relapse rates. CONCLUSIONS: SABU appears to be secondary to SAB in some cases while it is the primary infection causing SAB in others. In patients with SAB of non-urinary tract origin SABU should probably be regarded as distant haematogenous seeding and a marker of deep tissue dissemination, thus affecting general management and treatment duration. PMID- 22051917 TI - Reversed sex change by widowed males in polygynous and protogynous fishes: female removal experiments in the field. AB - Sex change, either protogyny (female to male) or protandry (male to female), is well known among fishes, but evidence of bidirectional sex change or reversed sex change in natural populations is still very limited. This is the first report on female removal experiments for polygnous and protogynous fish species to induce reversed sex change in the widowed males in the field. We removed all of the females and juveniles from the territories of dominant males in the cleaner wrasse Labroides dimidiatus (Labridae) and the rusty angelfish Centropyge ferrugata (Pomacanthidae) on the coral reefs of Okinawa. In both species, if new females or juveniles did not immigrate into the territories of the widowed males, some of them emigrated to form male-male pairs. When a male-male pair formed, the smaller, subordinate partner began to perform female sexual behaviours (n = 4 in L. dimidiatus; n = 2 in C. ferrugata) and, finally, released eggs (n = 1, respectively). Thus, the reversed sex change occurred in the widowed males according to the change of their social status. These results suggest that such female removal experiments will contribute to the discovery of reversed sex change in the field also in other polygnous and protogynous species. PMID- 22051918 TI - 4'-Alkoxy oligodeoxynucleotides: a novel class of RNA mimics. AB - 4'-Alkoxy-oligothymidylates were prepared as model compounds to study the influence of a C4'-alkoxy group on hybridisation. The phosphodiester homooligomers (15 units long) containing either a 4'-methoxy or 4'-(2 methoxyethoxy) group were found to display increased hybridisation with both dA(15) and rA(15) complementary counterparts compared to the natural oligothymidylate. In addition, we found their hybridisation behaviour to be similar to that of the regioisomeric 2'-O-methyl-oligothymidylate. The formed complexes (duplexes and triplexes) were studied using UV spectroscopy and polyacrylamide gel electrophoresis (PAGE). Structural background of the hybridization behaviour was examined using NMR and MDS. The favourable hybridisation properties of the 4'-alkoxyoligothymidylates indicated that 4' alkoxy modified nucleotides are promising compounds for the assembly of chimeric oligonucleotides with tunable properties. PMID- 22051920 TI - Late onset neutropenia associated with clozapine. PMID- 22051921 TI - Delusional parasitosis associated with donepezil. PMID- 22051922 TI - Imipramine for enuresis associated with risperidone. PMID- 22051923 TI - Positive impact of the beta-blocker celiprolol on panic, anxiety, and cardiovascular parameters in patients with mitral valve prolapse syndrome. PMID- 22051924 TI - Beta blockers for violence prophylaxis: case reports. PMID- 22051925 TI - Memantine for posttraumatic stress disorder in an older veteran. PMID- 22051929 TI - Electronic conductivity of Ce0.9Gd0.1O(1.95-delta) and Ce0.8Pr0.2O(2-delta): Hebb Wagner polarisation in the case of redox active dopants and interference. AB - The electronic conductivity of Ce(0.9)Gd(0.1)O(1.95-delta) and Ce(0.8)Pr(0.2)O(2 delta) under suppressed ionic flow was measured as a function of pO(2) in the range from 10(3) atm to 10(-17) atm for temperatures between 600 degrees C and 900 degrees C by means of Hebb-Wagner polarisation. The steady state I-V curve of Ce(0.9)Gd(0.1)O(1.95-delta) could be well described by the standard Hebb Wagner equation [M. H. Hebb, J. Chem. Phys., 1952, 20, 185; C. Wagner, Z. Elektrochem., 1956, 60, 4], yielding expressions for the n- and p-type conductivity as a function of pO(2). On the other hand, significant deviation of the steady state I-V curve from the standard Hebb-Wagner equation was observed for the case of Ce(0.8)Pr(0.2)O(2-delta). It is shown that the I-V curve can be successfully reproduced when the presence of the redox active dopant, Pr(3+)/Pr(4+), is taken into account, whereas even better agreement can be reached when further taking into account the interference between the ionic and electronic flows [C. Chatzichristodoulou, W.-S. Park, H.-S. Kim, P. V. Hendriksen and H.-I. Yoo, Phys. Chem. Chem. Phys., 2010, 12, 33]. Expressions are deduced for the small polaron mobilities in the Ce 4f and Pr 4f bands of Ce(0.8)Pr(0.2)O(2-delta). PMID- 22051930 TI - Polysomnography in stable COPD under non-invasive ventilation to reduce patient ventilator asynchrony and morning breathlessness. AB - BACKGROUND: Stable severe chronic obstructive pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure treated by nocturnal bi-level positive pressure non-invasive ventilation (NIV) may experience severe morning deventilation dyspnea. We hypothesised that in these patients, progressive hyperinflation, resulting from inappropriate ventilator settings, leads to patient-ventilator asynchrony (PVA) with a high rate of unrewarded inspiratory efforts and morning discomfort. METHODS: Polysomnography (PSG), diaphragm electromyogram and transcutaneous capnography (PtcCO(2)) under NIV during two consecutive nights using baseline ventilator settings on the first night, then, during the second night, adjustment of ventilator parameters under PSG with assessment of impact of settings changes on sleep, patient-ventilator synchronisation, morning arterial blood gases and morning dyspnea. RESULTS: Eight patients (61 +/- 8 years, FEV(1) 30 +/- 8% predicted, residual volume 210 +/- 30% predicted) were included. In all patients, pressure support was decreased during setting adjustments, as well as tidal volume, while respiratory rate increased without any deleterious effect on nocturnal PtcCO(2) or morning PaCO(2). PVA index, initially high (40 +/- 30%) during the baseline night, decreased significantly after adjusting ventilator settings (p = 0.0009), as well as subjective perception of PVA leaks, and morning dyspnea while quality of sleep improved. CONCLUSION: The subgroup of COPD patients treated by home NIV, who present marked deventilation dyspnea and unrewarded efforts may benefit from adjustment of ventilator settings under PSG or polygraphy. PMID- 22051931 TI - Optimism and prostate cancer-specific expectations predict better quality of life after robotic prostatectomy. AB - We examined the relations among generalized positive expectations (optimism), prostate-cancer specific expectations, and prostate cancer-related quality of life in a prospective sample of 83 men who underwent robotic assisted laparoscopic prostatectomy (RALP) for prostate cancer. Optimism was significantly associated with higher prostate cancer-specific expectations, beta = .36, p < .001. In addition, optimism and prostate cancer-specific expectations were independent prospective predictors of better scores on the following prostate cancer-related quality of life scales: Sexual Intimacy and Sexual Confidence; Masculine Self-Esteem (specific expectations only), Health Worry, Cancer Control, and Informed Decision Making (betas > .21, ps < .05). When considered simultaneously, both optimism and specific expectations contributed uniquely to better Health Worry and Cancer Control scores, optimism was a unique predictor of better Sexual Intimacy and Sexual Confidence scores, and specific expectations uniquely predicted higher scores on Informed Decision Making. Although optimism and prostate-cancer specific expectations are related, they contribute uniquely to several prostate cancer-related quality of life outcomes following RALP and may be important targets for quality of life research with this population. PMID- 22051932 TI - Phenolic compounds from Allium schoenoprasum, Tragopogon pratensis and Rumex acetosa and their antiproliferative effects. AB - Experimental studies have shown that phenolic compounds have antiproliferative and tumour arresting effects. The aim of this original study was to investigate the content of phenolic compounds (PhC) in flowers of Allium schoenoprasum (chive), Tragopogon pratensis (meadow salsify) and Rumex acetosa (common sorrel) and their effect on proliferation of HaCaT cells. Antiproliferative effects were evaluated in vitro using the following concentrations of phenolic compounds in cultivation medium: 100, 75, 50 and 25 ug/mL. Phenolic composition was also determined by HPLC. The results indicate that even low concentrations of these flowers' phenolic compounds inhibited cell proliferation significantly and the possible use of the studied herb's flowers as sources of active phenolic compounds for human nutrition. PMID- 22051933 TI - Berberine and itraconazole are not synergistic in vitro against Aspergillus fumigatus isolated from clinical patients. AB - The incidence of Aspergillus fumigatus infections has become more frequent as a consequence of widespread immunosuppression. At present, the number of available antifungal agents in the clinic is limited, and most of them, such as itraconazole (ICZ), are toxic and show resistance. Berberine (BER) is a plant alkaloid used in the clinic mainly for alimentary infections. We have used BER and ICZ to measure in vitro resistance in A. fumigatus isolated from clinical patients. The minimum inhibitory concentration ranges of BER and ICZ were 4-256 and 0.031-0.250 MUg/mL, respectively. In addition, against A. fumigatus IFM 40808 strain, the MIC50 values of BER and ICZ were 8 and 0.125 MUg/mL. Using this strain, we compared the giant colonies with or without BER, and concluded that BER could restrain A. fumigatus mycelial growth and conidial pigment production. Combinations of the two drugs were also tested by the checkerboard assay to identify any functional interactions between them. Thirty-two out of 42 isolates had FICI values > 4.0, indicating that two drugs were mutually antagonistic. In conclusion, it is not advised that BER and ICZ be used in the clinic at the same time. Our results indicated that BER may inhibit A. fumigatus through the ergosterol biosynthesis pathway, like ICZ. PMID- 22051934 TI - Icariside II enhances Nrf2 nuclear translocation to upregulate phase II detoxifying enzyme expression coupled with the ERK, Akt and JNK signaling pathways. AB - In the present study, the potent inducers of phase II detoxifying and antioxidant stress responsive to icariside II was investigated. First, a dose of 0-10 uM icariside II showed no significantly cytotoxicity on HepG2 cells by MTT assays and icariside II could enhance cellular GSH levels by ELISA assay. Then, the potential roles of ERK, Akt and JNK in the regulation of icariside II-induced Nrf2-dependent ARE transcriptional activity as well as ARE-mediated endogenous HO 1 and glutathione GST protein expression in HepG2 cells were estimated. Icariside II activated the nuclear translocation of Nrf2 and the up-regulated expression of Nrf2-related antioxidant protein OH-1 and GST were evaluated by Western blotting. Then the phosphorylation levels of ERK1/2, Akt and JNK1/2 were further examined by Western blotting assays. Results showed that icariside II significantly increased the phosphorylation levels of ERK1/2, Akt and JNK1/2. Furthermore, icariside II-induced ARE transcriptional activity was attenuated by the inhibition of ERK, Akt and JNK signaling using biochemical inhibitors. These results suggest that the Nrf2/ARE pathway plays an important role in the regulation of icariside-mediated antioxidant effects in HepG2 cells. PMID- 22051935 TI - Optimization of the conditions for extraction of serine protease from kesinai plant (Streblus asper) leaves using response surface methodology. AB - Response surface methodology (RSM) using a central composite design (CCD) was employed to optimize the conditions for extraction of serine protease from kesinai (Streblus asper) leaves. The effect of independent variables, namely temperature (42.5,47.5, X1), mixing time (2-6 min, X2), buffer content (0-80 mL, X3) and buffer pH (4.5-10.5, X4) on specific activity, storage stability, temperature and oxidizing agent stability of serine protease from kesinai leaves was investigated. The study demonstrated that use of the optimum temperature, mixing time, buffer content and buffer pH conditions protected serine protease during extraction, as demonstrated by low activity loss. It was found that the interaction effect of mixing time and buffer content improved the serine protease stability, and the buffer pH had the most significant effect on the specific activity of the enzyme. The most desirable conditions of 2.5 degrees C temperature, 4 min mixing time, 40 mL buffer at pH 7.5 was established for serine protease extraction from kesinai leaves. PMID- 22051936 TI - Choosing a health care provider. AB - In a consumer-driven health care model, consumers, armed with information, would select providers based on quality and cost, thus increasing competition. This synthesis examines the availability of quality information and the evidence of how consumers use such information to choose a provider. Key findings include: information is publicly available from multiple sources regarding hospitals, but not individual doctors. Hospital information is predominantly made available online; but this limits awareness and access. Awareness is low overall, but highest among well-educated, healthy people. Even when consumers are aware of the data available, they rarely use it because they do not find it relevant: they do not foresee needing a hospital soon; are happy with their current provider; or did not find information pertinent to their specific health condition or hospital. While there is some evidence that hospitals that do poorly on public quality scorecards lose market share, there is better evidence that the providers themselves react to the quality scores by addressing care problems. Studies consistently show that consumers value health care quality and want information, but instead they rely on input from friends, family and their personal physicians about the quality of providers. PMID- 22051937 TI - Bimodal actions of selenium essential for antioxidant and toxic pro-oxidant activities: the selenium paradox (Review). AB - Selenium is an essential biological trace element. Adult daily intake of selenium should be approximately 100 ug per day. This compound has a two-sided effect depending on its concentration. A selenium-deficient diet is associated with various endemic diseases, including cardiomuscular malfunctions, osteoarthritis, cancer and viral infections that lead to premature death. These defects are prevented when dietary intake of selenium is adequate. The preventive biological effect of selenium is considered to be due to the antioxidant function of selenoproteins with a selenocysteine in the active site of the catalytic domain. Antioxidant selenoproteins maintain the intracellular redox status and, as a result, normal physiological processes in the cell. Conversely, an overdose of selenium generates oxygen radicals and leads to apoptotic cell death by inducing oxidation and cross-linking of protein thiol groups essential for cell survival. A lower redox state caused by selenium may be implicated in toxic diseases, such as alkali disease and blind staggers. Collectively, selenium seems to have both harmful and beneficial attributes. The aim of this review is to summarize the various biological functions of selenium and to illustrate its opposite roles as a pro-oxidant and an antioxidant. PMID- 22051938 TI - GB virus C (GBV-C) evolutionary patterns revealed by analyses of reference genomes, E2 and NS5B sequences amplified from viral strains circulating in the Lisbon area (Portugal). AB - GBV-C is a non-pathogenic virus that is largely dispersed in different human populations. The phylogenetic analysis of the 5'-untranslated region (5'UTR) of the GBV-C genome has led to the segregation of viral strains into six genotypes, but incongruent results are frequently obtained depending on the genome region analyzed. In this report, different phylogenetic approaches and multivariate statistics were combined to disclose evolutionary patterns that contribute to shape GBV-C evolution. The data here presented indicate: (i) that the phylogenetic noise was mostly determined by the size of the analyzed sequence, rather than by its position on the viral genome; (ii) that most genomic segments in the coding sequence seemed to evolve under a similar evolution model, which was different from that which best fits the 5'UTR, with overall large heterogeneity of rate change across the sequence; (iii) that due to saturation of transversions occurring in the 5'UTR at genetic distances <0.10, care should be taken in drawing conclusions about the tree topologies involving the deeper branches, especially when using distance-based methods; (iv) that a non-uniform distribution of InSi and dS occurs over the viral ORF highlighting regions of the viral genome with remarkably low levels of silent substitutions, and implying that the observed differences may contribute to the detected phylogenetic incongruences; and finally (v) that genetic recombination clearly impacts the GBV C evolution extensively, this being shown for both reference genomes and NS5B GBV C sequences amplified from Portuguese residents. PMID- 22051939 TI - Coagulation and inflammation--close allies in health and disease. AB - The integrity of our bodies is under constant threat by external forces. Blood coagulation and inflammatory pathways are important, highly efficient defence systems that support health and well-being in both normal and challenged conditions. Being potentially dangerous for the own organism, they are kept under strict control by anticoagulant and anti-inflammatory mechanisms. Coagulation and inflammatory pathways are closely integrated by extensive crosstalk and tend to function in concert. They comprise a large number of cellular and molecular actors, which interact in extremely complex manners. A basic principle governing these interactions is the mutual activation of the pathways. Thus, the activation of coagulation leads to concomitant activation of inflammatory pathways, mirrored by the initiation of coagulation by inflammatory pathways. Efficient anticoagulant systems not only keep coagulation reactions under strict control but also exert control on inflammatory reactions. During inflammation, these anticoagulant/anti-inflammatory systems are repressed allowing full activation of coagulation and inflammation. Dysregulation of the delicate balance between these systems contributes to the pathogenesis of many diseases. PMID- 22051940 TI - One-year results of the Think Health! study of weight management in primary care practices. AB - The Think Health! study evaluated a behavioral weight loss program adapted from the Diabetes Prevention Program (DPP) lifestyle intervention to assist primary care providers (PCPs) and auxiliary staff acting as lifestyle coaches (LCs) in offering weight loss counseling to their patients. In a randomized trial conducted at five clinical sites, study participants were randomly assigned in a 1:1 ratio within each site to either "Basic Plus" (n = 137), which offered PCP counseling every 4 months plus monthly LC visits during the first year of treatment, or "Basic" (n = 124), which offered only PCP counseling every 4 months. Participants were primarily (84%) female, 65% African American, 16% Hispanic American, and 19% white. In the 72% of participants in each treatment group with a 12-month weight measurement, mean (95% CI) 1-year weight changes (kg) were -1.61 (-2.68, -0.53) in Basic Plus and -0.62 (-1.45, 0.20) in Basic (difference: 0.98 (-0.36, 2.33); P = 0.15). Results were similar in model-based estimates using all available weight data for randomized participants, adjusting for potential confounders. More Basic Plus (22.5%) than Basic (10.2%) participants lost >= 5% of their baseline weight (P = 0.022). In a descriptive, nonrandomized analysis that also considered incomplete visit attendance, mean weight change was -3.3 kg in Basic Plus participants who attended >= 5 LC visits vs. + 0.53 kg in those attending <5 LC visits. We conclude that the Basic Plus approach of moderate-intensity counseling by PCPs and their staff can facilitate modest weight loss, with clinically significant weight loss in high program attenders. PMID- 22051941 TI - Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). AB - A 56-week randomized controlled trial was conducted to evaluate safety and efficacy of a controlled-release combination of phentermine and topiramate (PHEN/TPM CR) for weight loss (WL) and metabolic improvements. Men and women with class II and III obesity (BMI >= 35 kg/m(2)) were randomized to placebo, PHEN/TPM CR 3.75/23 mg, or PHEN/TPM CR 15/92 mg, added to a reduced-energy diet. Primary end points were percent WL and proportions of patients achieving 5% WL. Secondary end points included waist circumference (WC), systolic and diastolic blood pressure (BP), fasting glucose, and lipid measures. In the primary analysis (randomized patients with at least one postbaseline weight measurement who took at least one dose of assigned drug or placebo), patients in the placebo, 3.75/23, and 15/92 groups lost 1.6%, 5.1%, and 10.9% of baseline body weight (BW), respectively, at 56 weeks (P < 0.0001). In categorical analysis, 17.3% of placebo patients, 44.9% of 3.75/23 patients, and 66.7% of 15/92 patients, lost at least 5% of baseline BW at 56 weeks (P < 0.0001). The 15/92 group had significantly greater changes relative to placebo for WC, systolic and diastolic BP, fasting glucose, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The most common adverse events were paresthesia, dry mouth, constipation, dysgeusia, and insomnia. Dropout rate from the study was 47.1% for placebo patients, 39.0% for 3.75/23 patients, and 33.6% of 15/92 patients. PHEN/TPM CR demonstrated dose-dependent effects on weight and metabolic variables in the direction expected to be beneficial with no evidence of serious adverse events induced by treatment. PMID- 22051942 TI - Contributions of Philip Teitelbaum to affective neuroscience. AB - As part of a festschrift issue for Philip Teitelbaum, I offer here the thesis that Teitelbaum deserves to be viewed as an important forefather to the contemporary field of affective neuroscience (which studies motivation, emotion and affect in the brain). Teitelbaum's groundbreaking analyses of motivation deficits induced by lateral hypothalamic damage, of roles of food palatability in revealing residual function, and of recovery of 'lost' functions helped shape modern understanding of how motivation circuits operate within the brain. His redefinition of the minimum requirement for identifying motivation raised the conceptual bar for thinking about the topic among behavioral neuroscientists. His meticulous analyses of patterned stages induced by brain manipulations, life development and clinical disorders added new dimensions to our appreciation of how brain systems work. His steadfast highlighting of integrative functions and behavioral complexity helped provide a healthy functionalist counterbalance to reductionist trends in science of the late 20th century. In short, Philip Teitelbaum can be seen to have made remarkable contributions to several domains of psychology and neuroscience, including affective neuroscience. PMID- 22051943 TI - The effects of MyD88 deficiency on exploratory activity, anxiety, motor coordination, and spatial learning in C57BL/6 and APPswe/PS1dE9 mice. AB - Toll-like receptors (TLRs) are a family of pattern-recognition receptors in innate immunity and provide a first line defense against pathogens and tissue injuries. In addition to important roles in infection, inflammation, and immune diseases, recent studies show that TLR signaling is involved in modulation of learning, memory, mood, and neurogenesis. Because MyD88 is essential for the downstream signaling of all TLRs, except TLR3, we investigated the effects of MyD88 deficiency (MyD88-/-) on behavioral functions in mice. Additionally, we recently demonstrated that a mouse model of Alzheimer's disease (AD) deficient for MyD88 had decreases in Abeta deposits and soluble Abeta in the brain as compared with MyD88 sufficient AD mouse models. Because accumulation of Abeta in the brain is postulated to be a causal event leading to cognitive deficits in AD, we investigated the effects of MyD88 deficiency on behavioral functions in the AD mouse model at 10 months of age. MyD88 deficient mice showed more anxiety in the elevated plus-maze. In the motor coordination tests, MyD88 deficient mice remained on a beam and a bar for a longer time, but with slower initial movement on the bar. In the Morris water maze test, MyD88 deficiency appeared to improve spatial learning irrespective of the transgene. Our findings suggest that the MyD88-dependent pathway contributes to behavioral functions in an AD mouse model and its control group. PMID- 22051945 TI - Two new compounds, beta-ScTe and Y3Au2, and a reassessment of Y2Au. AB - Two new compounds, beta-ScTe (scandium telluride) and Y(3)Au(2) (triyttrium digold), have been synthesized by high-temperature solid-state techniques and their crystal structures, along with that of Y(2)Au (diyttrium gold), have been refined by single-crystal X-ray diffraction methods. beta-ScTe is a superstructure of ScTe (NiAs-type), featuring double hexagonal close-packed layers of Te atoms with the octahedral cavities filled by Sc atoms. Y(3)Au(2) displays a U(3)Si(2)-type structure and is built from Au(2)-centered bitrigonal prisms and centered cubes of Y atoms. The structure of Y(2)Au is better described as an inverse PbCl(2)-type structure rather than a Co(2)Si-type. PMID- 22051944 TI - The role of social isolation in ethanol effects on the preweanling rat. AB - The present experiments investigated the effects of acute ethanol exposure on voluntary intake of 0.1% saccharin or water as well as behavioral and nociceptive reactivity in 12-day-old (P12) rats exposed to differing levels of isolation. The effects of ethanol emerged only during short-term social isolation (STSI) with different patterns observed in males and females and in pups exposed to saccharin or water. The 0.5g/kg ethanol dose selectively increased saccharin intake in females, decreased rearing activity in males and attenuated isolation-induced analgesia (IIA) in all water-exposed pups. Ingestion of saccharin decreased IIA, and the 0.5g/kg ethanol dose further reduced IIA. The 1.0g/kg ethanol dose, administered either intragastrically or intraparentionally, also decreased IIA in P12 females, but not in P9 pups. A significant correlation between voluntary saccharin intake and baseline nociceptive reactivity was revealed in saline injected animals, saccharin intake was inversely correlated with behavioral activation and latency of reaction to noxious heat after 0.5g/kg ethanol in females. The 0.5g/kg ethanol dose did not affect plasma corticosterone (CORT) measured 5h after maternal separation or 20min after ethanol injection. Female pups CORT level was inversely correlated with magnitude of IIA that accompanied the first episode of STSI (pretest isolation) 1.5-2h before CORT measurement. The present findings suggest that the anxiolytic properties of ethanol are responsible for enhancement of saccharin intake during STSI. Furthermore, differential reactivity of P12 males and females to STSI plays an important role in ethanol effects observed at this age. PMID- 22051946 TI - A spin-frustrated cobalt(II) carbonate pyrochlore network. AB - The crystal structure of the cobalt(II) carbonate-based compound cobalt(II) dicarbonate trisodium chloride, Co(CO(3))(2)Na(3)Cl, grown from a water-ethanol mixture, exhibits a three-dimensional network of corner-sharing {Co(4)(MU(3) CO(3))(4)} tetrahedral building blocks, in which the Co(II) centres define a pyrochlore lattice and reside in a slightly distorted octahedral Co(O-CO(2))(6) environment. The space outside the hexagonal framework defined by these interlinked groups is occupied by Na(+) and Cl(-) ions. Antiferromagnetic coupling between adjacent Co(II) centres, mediated by carbonate bridges, results in geometric spin frustration which is typical for pyrochlore networks. The Co and Cl atoms reside on the special position 3, one Na atom on position 2 and a carbonate C atom on position 3. PMID- 22051947 TI - Poly[(MU4-adamantane-1,3-dicarboxylato-kappa5O1:O1':O3,O3':O3')(MU3-adamantane 1,3-dicarboxylato-kappa5O1,O1':O3,O3':O3')dimagnesium]: a layered coordination polymer. AB - The title compound, [Mg(2)(C(12)H(14)O(4))(2)](n), is the first example of an s block metal adamantanedicarboxylate coordination polymer. The asymmetric unit comprises two crystallographically unique Mg(II) centers and two adamantane-1,3 dicarboxylate ligands. The compound is constructed from a combination of chains of corner-sharing magnesium-centered polyhedra, parallel to the a axis, connected by organic linkers to form a layered polymer. The two Mg(II) centers are present in distorted tetrahedral and octahedral coordination environments derived from carboxylate O atoms. Tetrahedrally coordinated Mg(II) centers have been reported in organometallic compounds, but this is the first time that such coordination has been observed in a magnesium-based coordination polymer. The bond valance sums of the two Mg(II) centers are 2.05 and 2.11 valence units, matching well with the expected value of 2. PMID- 22051948 TI - Two new transition metal inorganic-organic hybrid borates: [tris(2 aminoethoxy)trihydroxyhexaborato]cobalt(II) and its nickel(II) analogue. AB - The two isomorphous title compounds, [1,5,9-tris(2-aminoethoxy)-3,7,11-trihydroxy 3,7,11-tribora-1,5,9-triborata-2,4,6,8,10,12-hexaoxa-13 oxoniatricyclo[7.3.1.0(5,13)]tridecane]cobalt(II), [Co(C(6)H(21)B(6)N(3)O(13))] or Co{B(6)O(7)(OH)(3)[O(CH(2))(2)NH(2)](3)}, and the Ni(II) analogue, [Ni(C(6)H(21)B(6)N(3)O(13))], each consist of an M(II) cation and an inorganic organic hybrid {B(6)O(7)(OH)(3)[O(CH(2))(2)NH(2)](3)}(2-) anion. The M(II) cation lies on a crystallographic threefold axis (as does one O atom) and is octahedrally coordinated by three N atoms from the organic component. Three O atoms covalently link the B-O cluster and the organic component. Molecules are connected to one another through N-H...O and O-H...O hydrogen bonds, forming a three-dimensional supramolecular network. PMID- 22051949 TI - Poly[[MU3-2-(carboxylatomethyl)benzoato-kappa3O1:O2:O2]bis(1H-imidazole kappaN3)copper(II)]. AB - In the title polymeric compound, [Cu(C(9)H(6)O(4))(C(3)H(4)N(2))(2)](n), the copper(II) cation occupies an N(2)O(3) coordination sphere defined by two 1H imidazole (imid) ligands in trans positions and three carboxylate O atoms from three different 2-(carboxylatomethyl)benzoate (hpt(2-)) dianions. The geometry is that of a square pyramid with one of the O atoms at the apex, bridging neighbouring metal centres into an [-ON(2)CuO(2)CuN(2)O-] dinuclear unit. These units are in turn connected by hpt anions into a reticular mesh topologically characterized by two types of loops, viz. a four-membered Cu(2)O(2) diamond motif and a 32-membered Cu(4)O(8)C(20) ring. The imid groups do not take part in the formation of the two-dimensional structure, but take part in the N-H...O interactions. These arise only within individual planes, interplanar interactions being only of the van der Waals type. PMID- 22051950 TI - Two mononuclear octahedral complexes with benzimidazole-2-carboxylate: supramolecular networks constructed by hydrogen bonds. AB - The title compounds, trans-bis(1H-benzimidazole-2-carboxylato kappa(2)N(3),O)bis(ethanol-kappaO)cadmium(II), [Cd(C(8)H(5)N(2)O(2))(2)(C(2)H(6)O)(2)], (I), and trans-bis(1H-benzimidazole kappaN(3))bis(1H-benzimidazole-2-carboxylato-kappa(2)N(3),O)nickel(II), [Ni(C(8)H(5)N(2)O(2))(2)(C(7)H(6)N(2))(2)], (II), are hydrogen-bonded supramolecular complexes. In (I), the Cd(II) ion is six-coordinated by two O atoms from two ethanol molecules, and by two O and two N atoms from two bidentate benzimidazole-2-carboxylate (HBIC) ligands, giving a distorted octahedral geometry. The combination of O-H...O and N-H...O hydrogen bonds results in two dimensional layers parallel to the ab plane. In (II), the six-coordinated Ni(II) atom, which lies on an inversion centre, shows a similar distorted octahedral geometry to the Cd(II) ion in (I); two benzimidazole molecules occupy the axial sites and the equatorial plane contains two chelating HBIC ligands. Pairs of N H...O hydrogen bonds between pairs of HBIC anions connect adjacent Ni(II) coordination units to form a one-dimensional chain parallel to the a axis. Moreover, these one-dimensional chains are further linked via N-H...O hydrogen bonds between HBIC anions and benzimidazole molecules to generate a three dimensional supramolecular framework. The two compounds show quite different supramolecular networks, which may be explained by the fact that different co ligands occupy the axial sites in the coordination units. PMID- 22051951 TI - (eta5-Cyclopentadienyl)(eta6-phenoxathiin 10,10-dioxide)iron(II) hexafluoridophosphate and phenoxathiin 10,10-dioxide. AB - In the structure of the title complex salt, [Fe(C(5)H(5))(C(12)H(8)O(3)S)]PF(6), the coordinated cyclopentadienyl (Cp) and benzene ring planes are almost parallel, with a hinge angle between the planes of 0.8 (2) degrees . The hinge angle between the planes of the peripheral (coordinated and uncoordinated) benzene rings in the coordinated phenoxathiin 10,10-dioxide molecule is 169.9 (2) degrees , and the FeCp moiety is located inside the shallow fold of the heterocycle. The hinge angle between the benzene ring planes in the free heterocycle, C(12)H(8)O(3)S, is 171.49 (6) degrees . PMID- 22051952 TI - A rhodium(III) complex of the linear diborazine H3B.NMe2BH2.NMe2H: an intermediate in the dehydrocoupling of H3B.NMe2H. AB - The solid-state structure of the rhodium complex (dimethylamine dimethylaminoborane-borane-kappa(2)H,H')dihydridobis(triisopropylphosphane kappaP)rhodium(III) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, [RhH(2)(C(4)H(18)B(2)N(2))(C(9)H(21)P)(2)](C(32)H(12)BF(24)), is reported. The complex contains the linear diborazine H(3)B.NMe(2)BH(2).NMe(2)H, a kinetically important intermediate in the transition-metal-mediated dehydrocoupling of H(3)B.NMe(2)H, ultimately affording the dimeric amino-borane [H(2)BNMe(2)](2). The structure of the title complex contains a distorted octahedral Rh(III) centre, with mutually trans phosphane ligands and cis hydride ligands. The diborazine is bound through two Rh-H-B sigma-bonds and exhibits a gauche conformation with respect to the B-N-B-N backbone. PMID- 22051953 TI - A square two-dimensional polymer of cobalt citrate cubanes. AB - The structure of the title complex, poly[dicaesium(I) hexaaquacobalt(II) [octaaquatetra-MU-citrato-hexacobalt(II)] dodecahydrate], {Cs(2)[Co(H(2)O)(6)][Co(6)(C(6)H(4)O(7))(4)(H(2)O)(8)].12H(2)O}(n), at 100 (1) K is formed by layers of a square two-dimensional polymer composed of Co(II) citrate cubanes bridged by magnetically active six-coordinate Co(II) cations. The polymer has plane symmetry p4mm in the c-axis projection. The cubanes reside on sites of crystallographic symmetry 4, while the bridging Co(II) centres lie on twofold axes. The basic polymeric unit has a charge of 4-, balanced by two Cs(+) and a [Co(H(2)O)(6)](2+) (symmetry -4) cation, which lie in channels between the polymeric layers. Unligated water molecules, of which there are 12 per cubane, enter into an extended intralayer and layer-bridging hydrogen-bond pattern, which can be described in detail even though not all of the H atoms of the water molecules were located. PMID- 22051954 TI - The coordination polymer poly[bis[MU2-2-(2,2'-bi-1H-imidazol-1 yl)acetato]cadmium]. AB - The title compound, [Cd(C(8)H(7)N(4)O(2))(2)](n), crystallizes in the centrosymmetric triclinic space group P1 with an asymmetric unit consisting of a bivalent Cd(II) atom and two 2-(2,2'-bi-1H-imidazol-1-yl)acetate (BDAC(-)) anions. Two inversion-related BDAC(-) ligands are oppositely arranged and bind two Cd(II) ions to form a [Cd(2)(BDAC)(2)] rhomboid subunit which is bridged by another BDAC(-) ligand to form an infinite ladder along the a direction containing parallelogram grids. The three-dimensional supramolecular architecture is formed by hydrogen bonds and C-H...pi and pi-pi interactions. PMID- 22051955 TI - Poly[4,4'-(propane-1,3-diyl)dipyridinium bis{tetraaquabis(MU2-5-carboxybenzene 1,2,4-tricarboxylato)bis[MU2-1,3-bis(4-pyridyl)propane]dicobalt(II)} pentahydrate]. AB - The title polymeric compound, {(C(13)H(16)N(2))[Co(C(10)H(3)O(8))(C(13)H(14)N(2))(H(2)O)(2)](2).5H(2)O}(n), is an ionic structure comprising an anionic two-dimensional mesh characterized by a {[Co(Hbtc)(bpp)(H(2)O)(2)](-)}(2) motif [Hbtc is 5-carboxybenzene-1,2,4 tricarboxylate and bpp is 1,3-bis(4-pyridyl)propane], with interspersed 4,4' (propane-1,3-diyl)dipyridinium cations, denoted (H(2)bpp)(2+), and water molecules providing the charge balance and structure stabilization. The reticular mesh consists of two independent types of [Co(H(2)O)(2)](2+) cationic nodes (lying on inversion centres), interconnected in the [101] direction by two independent sets of neutral bridging bpp ligands, both types of ligands being split by non-equivalent twofold axes. One set is formed by genuinely symmetric moieties, while those in the second set are only symmetric by disorder in the central propane bridge. These chains contain only one type of Co(II) centre and one type of bpp ligand; the metal cations therein are laterally bridged by Hbtc anions, thus forming transverse chains of alternating types of Co(II) cations. The elemental motif of the resulting grid is a highly distorted parallelogram, with metal-metal distances of 13.5242 (14) A in the bpp direction and 9.105 (2) A in the Hbtc direction, and a large internal angle of 138.42 (18) degrees . These two-dimensional structures have a profusion of hydrogen-bonding interactions with each other, either directly (with the aqua molecules as donors and the Hbtc anions as acceptors) or mediated by the unbound (H(2)bpp)(2+) cations and water molecules of hydration. These interactions generate a very complex hydrogen bonding scheme involving all of the available N-H and O-H groups and which links these two-dimensional grids into a three-dimensional network. PMID- 22051956 TI - (Z)-3-Methyl-N-(7-nitroacridin-3-yl)-2,3-dihydro-1,3-benzothiazol-2-imine from laboratory powder diffraction data. AB - The title compound, C(21)H(14)N(4)O(2)S, belongs to a family of molecules possessing nonlinear optical properties in solution. Its structure has been solved from laboratory X-ray powder diffraction data using a new direct-space structure solution method, where the atomic coordinates are directly used as parameters and the molecular geometry is described by restraints. The molecular packing is controlled by two systems of pi-pi interactions and one weak edge-to face interaction. PMID- 22051957 TI - A new polymorph and two pseudopolymorphs of pyrimethamine. AB - Due to its donor-acceptor-donor site, the antimalarial drug pyrimethamine [systematic name: 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine] is a potential component of a supramolecular synthon. During a cocrystallization screen, one new polymorph of solvent-free pyrimethamine, C(12)H(13)ClN(4), (I), and two pseudopolymorphs, pyrimethamine dimethyl sulfoxide monosolvate, C(12)H(13)ClN(4).C(2)H(6)OS, (Ia), and pyrimethamine N-methylpyrrolidin-2-one monosolvate, C(12)H(13)ClN(4).C(5)H(9)NO, (Ib), were obtained. In (I), (Ia), (Ib) and the previously reported polymorph, the pyrimethamine molecules exhibit similar conformations and form R(2)(2)(8) dimers stabilized by a pair of N-H...N hydrogen bonds. However, the packing arrangements are completely different. In (I), the dimers are connected by two additional N-H...N hydrogen bonds to form ribbons and further connected into a two-dimensional network parallel to (100), while layers containing N-H...Cl hydrogen-bonded pyrimethamine ribbons are observed in the packing of the known polymorph. In the two pseudopolymorphs, two pyrimethamine molecules are linked to form R(2)(2)(8) dimers and the solvent molecules are connected to the dimers by R(2)(3)(8) interactions involving two N H...O hydrogen bonds. These arrangements are connected to form zigzag chains by N H...Cl interactions in (Ia) and to form ribbons by N-H...N interactions in (Ib). Unexpectedly, a reaction between pyrimethamine and N-methylpyrrolidin-2-one occurred during another cocrystallization experiment from a solvent mixture of N methylpyrrolidin-2-one and dimethyl sulfoxide, yielding solvent-free 5,5'-{[5-(4 chlorophenyl)-6-ethylpyrimidine-2,4-diyl]bis(azanediyl)}bis(1-methylpyrrolidin-2 one), C(22)H(27)ClN(6)O(2), (II). In the packing of (II), the pyrimethamine derivatives are N-H...O hydrogen bonded to form ribbons. A database study was carried out to compare the molecular conformations and hydrogen-bonding interactions of pyrimethamine. PMID- 22051958 TI - Comparison of racemic epi-inosose and (-)-epi-inosose. AB - The conversion of myo-inositol to epi-inositol can be achieved by the hydride reduction of an intermediate epi-inosose derived from myo-inositol. (-)-epi Inosose, (I), crystallized in the monoclinic space group P2(1), with two independent molecules in the asymmetric unit [Hosomi et al. (2000). Acta Cryst. C56, e584-e585]. On the other hand, (2RS,3SR,5SR,6SR)-epi-inosose, C(6)H(10)O(6), (II), crystallized in the orthorhombic space group Pca2(1). Interestingly, the conformation of the molecules in the two structures is nearly the same, the only difference being the orientation of the C-3 and C-4 hydroxy H atoms. As a result, the molecular organization achieved mainly through strong O-H...O hydrogen bonding in the racemic and homochiral lattices is similar. The compound also follows Wallach's rule, in that the racemic crystals are denser than the optically active form. PMID- 22051959 TI - Cocrystals of 6-propyl-2-thiouracil: N-H...O versus N-H...S hydrogen bonds. AB - In order to investigate the relative stability of N-H...O and N-H...S hydrogen bonds, we cocrystallized the antithyroid drug 6-propyl-2-thiouracil with two complementary heterocycles. In the cocrystal pyrimidin-2-amine-6-propyl-2 thiouracil (1/2), C(4)H(5)N(3).2C(7)H(10)N(2)OS, (I), the 'base pair' is connected by one N-H...S and one N-H...N hydrogen bond. Homodimers of 6-propyl-2 thiouracil linked by two N-H...S hydrogen bonds are observed in the cocrystal N (6-acetamidopyridin-2-yl)acetamide-6-propyl-2-thiouracil (1/2), C(9)H(11)N(3)O(2).2C(7)H(10)N(2)OS, (II). The crystal structure of 6-propyl-2 thiouracil itself, C(7)H(10)N(2)OS, (III), is stabilized by pairwise N-H...O and N-H...S hydrogen bonds. In all three structures, N-H...S hydrogen bonds occur only within R(2)(2)(8) patterns, whereas N-H...O hydrogen bonds tend to connect the homo- and heterodimers into extended networks. In agreement with related structures, the hydrogen-bonding capability of C=O and C=S groups seems to be comparable. PMID- 22051960 TI - The dithiolene ligand and tetrathiafulvalene precursor molecules 4,5 bis(bromomethyl)-1,3-dithiol-2-one and 4,5-bis[(dihydroxyphosphoryl)methyl]-1,3 dithiol-2-one. AB - The crystal structures of 4,5-bis(bromomethyl)-1,3-dithiol-2-one, C(5)H(4)Br(2)OS(2), (I), and 4,5-bis[(dihydroxyphosphoryl)methyl]-1,3-dithiol-2 one, C(5)H(8)O(7)P(2)S(2), (II), occur with similar unit cells in the same monoclinic space group. Both molecules reside on a twofold symmetry axis coincident with the C=O bond, so that the substituents in the 4- and 5-positions project above and below the plane of the 1,3-dithiol-2-one ring. In both structures, the molecules align themselves in a head-to-tail fashion along the b axis, and these rows of molecules then stack, with alternating directionality, along the c axis. For (II), an extensive network of intermolecular hydrogen bonds occurs between molecules within the same stack and between adjacent stacks. Each CH(2)P(O)(OH)(2) group participates in four hydrogen bonds, twice as donor and twice as acceptor. PMID- 22051961 TI - Conformations and resulting hydrogen-bonded networks of hydrogen {phosphono[(pyridin-1-ium-3-yl)amino]methyl}phosphonate and related 2-chloro and 6-chloro derivatives. AB - In the crystal structures of the conformational isomers hydrogen {phosphono[(pyridin-1-ium-3-yl)amino]methyl}phosphonate monohydrate (pro-E), C(6)H(10)N(2)O(6)P(2).H(2)O, (Ia), and hydrogen {phosphono[(pyridin-1-ium-3 yl)amino]methyl}phosphonate (pro-Z), C(6)H(10)N(2)O(6)P(2), (Ib), the related hydrogen {[(2-chloropyridin-1-ium-3-yl)amino](phosphono)methyl}phosphonate (pro E), C(6)H(9)ClN(2)O(6)P(2), (II), and the salt bis(6-chloropyridin-3-aminium) [hydrogen bis({[2-chloropyridin-1-ium-3-yl(0.5+)]amino}methylenediphosphonate)] (pro-Z), 2C(5)H(6)ClN(2)(+).C(12)H(16)Cl(2)N(4)O(12)P(4)(2-), (III), chain-chain interactions involving phosphono (-PO(3)H(2)) and phosphonate (-PO(3)H(-)) groups are dominant in determining the crystal packing. The crystals of (Ia) and (III) comprise similar ribbons, which are held together by N-H...O interactions, by water- or cation-mediated contacts, and by pi-pi interactions between the aromatic rings of adjacent zwitterions in (Ia), and those of the cations and anions in (III). The crystals of (Ib) and (II) have a layered architecture: the former exhibits highly corrugated monolayers perpendicular to the [100] direction, while in the latter, flat bilayers parallel to the (001) plane are formed. In both (Ib) and (II), the interlayer contacts are realised through N H...O hydrogen bonds and weak C-H...O interactions involving aromatic C atoms. PMID- 22051962 TI - Three new fluorinated N-phenyl-substituted pentacyclic ethanoanthracenedicarboximides. AB - Diels-Alder reaction between maleimides featuring 3,5-di-, 2,4,6-tri- and pentafluorinated N-phenyl substituents and anthracene yields the corresponding pentacyclic ethanoanthracenedicarboximide compounds, namely N-(3,5 difluorophenyl)-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboximide, C(24)H(15)F(2)NO(2), (IIa), N-(2,4,6-trifluorophenyl)-9,10-dihydro-9,10 ethanoanthracene-11,12-dicarboximide, C(24)H(14)F(3)NO(2), (IIb), N-(2,3,4,5,6 pentafluorophenyl)-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboximide, C(24)H(12)F(5)NO(2), (IIc). The crystal structures of (IIa)-(IIc) reveal an expected molecular geometry with a 'V'-shape of the anthracene-derived tricyclic moiety. The crystal packings of (IIa) and (IIb) are dominated by pi-pi and C H...O/F interactions, while F...F and C-H...pi contacts are absent. In contrast, (IIc) shows F...F and C-H...O/F contacts, but no pi-involved contacts of relevance. PMID- 22051964 TI - 4-[(Z)-2-(methylsulfanyl)ethenyl]-1-phenyl-1H-1,2,3-triazole: an order-disorder (OD) interpretation of twinning. AB - The title compound, C(11)H(11)SN(3), crystallizes as twins with a twin volume fraction of 0.4232 (13). An order-disorder (OD) interpretation gives a plausible explanation of the crystallization behaviour. The structure is a polytype with a maximum degree of order (MDO). The contact plane is interpreted as being composed of a fragment of the second MDO polytype. The planes of the triazole and phenyl rings are twisted by 36.88 (6) degrees . Molecules are connected via C-H...N hydrogen bonds, forming layers parallel to (100). The layers can be arranged in geometrically different but energetically virtually equivalent ways, giving rise to polytypism. PMID- 22051963 TI - Polymorphic form IV of olanzapine. AB - 2-Methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine, C(17)H(20)N(4)S, commonly known as olanzapine, is a psychotropic agent that belongs to the thienobenzodiazepine class of drugs. A new polymorph form IV was obtained upon attempted cocrystallization with nicotinamide in a 1:1 ratio from an ethyl acetate solution. Two butterfly-like molecules form centrosymmetric dimers stabilized by weak C-H...pi interactions between the 4-methylpiperazin-1 yl fragment and the benzene/thiophene aromatic system. Form IV consists of a herringbone arrangement of dimers, whereas the previously reported form II has parallel dimers. Both crystal structures are sustained by an N-H...N hydrogen bond. PMID- 22051965 TI - Powder X-ray study of racemic (2RS,3RS)-5-amino-3-[4-(3-methoxyphenyl)piperazin-1 yl]-1,2,3,4-tetrahydronaphthalen-2-ol. AB - The structure of the title benzovesamicol analogue, C(21)H(27)N(3)O(2), an important compound for the diagnosis of Alzheimer's disease, has been determined by X-ray powder diffraction. The title compound was firstly synthesized and characterized by spectroscopic methods (FT-IR, and (13)C and (1)H NMR). The compound is a racemic mixture of enantiomers which crystallizes in the monoclinic system in a centrosymmetric space group (P2(1)/c). Crystallography, in particular powder X-ray diffraction, was pivotal in revealing that the enantio-resolution did not succeed. The piperazine ring is in a chair conformation, while the cyclohexene ring assumes a half-chair conformation. The crystal packing is dominated by intermolecular O-H...N hydrogen bonding which links molecules along the c direction. PMID- 22051966 TI - Hydrogen-bonded structures of the isomeric compounds of phthalazine with 3-chloro 2-nitrobenzoic acid, 4-chloro-2-nitrobenzoic acid and 4-chloro-3-nitrobenzoic acid. AB - The structures of three isomeric compounds, C(7)H(4)ClNO(4).C(8)H(6)N(2), of phthalazine with chloro- and nitro-substituted benzoic acid, namely, 3-chloro-2 nitrobenzoic acid-phthalazine (1/1), (I), 4-chloro-2-nitrobenzoic acid phthalazine (1/1), (II), and 4-chloro-3-nitrobenzoic acid-phthalazine (1/1), (III), have been determined at 190 K. In the asymmetric unit of each compound, there are two crystallographically independent chloronitrobenzoic acid phthalazine units, in each of which the two components are held together by a short hydrogen bond between an N atom of the base and a carboxyl O atom. In one hydrogen-bonded unit of (I) and in two units of (II), a weak C-H...O interaction is also observed between the two components. The N...O distances are 2.5715 (15) and 2.5397 (17) A for (I), 2.5655 (13) and 2.6081 (13) A for (II), and 2.613 (2) and 2.589 (2) A for (III). In both hydrogen-bonded units of (I) and (II), the H atoms are each disordered over two positions with (N site):(O site) occupancies of 0.35 (3):0.65 (3) and 0.31 (3):0.69 (3) for (I), and 0.32 (3):0.68 (3) and 0.30 (3):0.70 (3) for (II). The H atoms in the hydrogen-bonded units of (III) are located at the O-atom sites. PMID- 22051967 TI - [New options for submission of manuscripts to Der Nervenarzt (The Neurologist)]. PMID- 22051968 TI - [Differential indications for psychotherapy exemplified by depression]. AB - The general efficacy of psychotherapeutic approaches in the treatment of mental disorders has been demonstrated by meta-analyses. Disorder-specific methods are increasingly dominating the field. In the field of depression psychological interventions have proven to be as equally effective as pharmacotherapy in mild and moderate depressives but with longer lasting effects after termination of treatment. The combination of both methods is particularly relevant for the therapy of severe and chronic depression. The indications should be differentiated beyond the severity and course of the disorder, e.g. according to previous traumatization, comorbidity, patient difficulty and the empirical evidence of the different approaches. PMID- 22051971 TI - Improving the definition of developmental delay. PMID- 22051972 TI - Electron delocalization and aromaticity in low-lying excited states of archetypal organic compounds. AB - Aromaticity is a property usually linked to the ground state of stable molecules. Although it is well-known that certain excited states are unquestionably aromatic, the aromaticity of excited states remains rather unexplored. To move one step forward in the comprehension of aromaticity in excited states, in this work we analyze the electron delocalization and aromaticity of a series of low lying excited states of cyclobutadiene, benzene, and cyclooctatetraene with different multiplicities at the CASSCF level by means of electron delocalization measures. While our results are in agreement with Baird's rule for the aromaticity of the lowest-lying triplet excited state in annulenes having 4npi electrons, they do not support Soncini and Fowler's generalization of Baird's rule pointing out that the lowest-lying quintet state of benzene and septet state of cyclooctatetraene are not aromatic. PMID- 22051973 TI - Anti-erythropoietin and anti-thrombopoietin antibodies induced after administration of recombinant human erythropoietin. AB - Recombinant human erythropoietin (rhEPO) has been successfully used for correcting renal anemia. However, recent studies have raised some concerns about the safety of rhEPO treatment due to its immunogenic side effect - pure red cell aplasia (PRCA). We now report a case of development of anti-EPO neutralizing antibodies (Abs) implicated in thrombocytopenia as well as erythrocytopenia. A 35 year-old man had a history of administering rhEPO (epoetin alfa, epoetin beta and darbepoetin alfa) for 2years to treat renal anemia. The hematological parameters were collected. Anti-EPO, anti-platelet, and anti-thrombopoietin (TPO) Ab assays were performed to test the presence of autoreactive Abs. After performing antibody assays due to severe resistance to rhEPO treatment, a high titer of anti EPO neutralizing Abs was detected. However, unexpectedly, this patient also showed thrombocytopenia rather than PRCA. We investigated the cause of the marked thrombocytopenia and found anti-TPO Abs in patient serum. To our best knowledge, this is the first report of the development of anti-TPO Abs during rhEPO treatment for anemia. PMID- 22051974 TI - Anti-tumor activity of immunomodulatory peptide alloferon-1 in mouse tumor transplantation model. AB - Alloferons are a group of antiviral and anti-tumor peptides primarily isolated from insects and stimulating cytotoxic activity of natural killer cells in mammals including mice and humans. Alloferon-1 is currently used in the treatment of persistent viral infections; however its anti-tumor potential needs further preclinical assessment. Here we evaluate alloferon-1 anti-tumor activity in DBA/2 mice grafted with syngenic P388 murine leukemia cells. Alloferon-1 was applied alone or in combination with conventional cytotoxic chemotherapy (a mixture of cyclophosphamide, doxorubicin and vincristine). Alloferon-1 monotherapy demonstrated moderate tumoristatic and tumoricidal activities comparable with low dose chemotherapy. When alloferon-1 and the cytotoxic drugs were combined in a regime of pulse immunochemotherapy the combination anti-tumor activity evidently exceeded that of the treatments applied individually. PMID- 22051975 TI - Comparative evaluation of anti-inflammatory properties of thymoquinone and curcumin using an asthmatic murine model. AB - This study was designed to compare the inhibitory effects of thymoquinone (TQ) and curcumin (CMN) on the biological changes associating asthma. TQ appeared to exhibit greater inhibitory effects on the aggregation of inflammatory cells in bronchoalveolar lavage (BAL) fluid and in lung tissues. We also measured the effects of the two agents on serum IgE and the changes in the mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1). Serum IgE was significantly decreased by TQ and CMN with TQ being more potent. Also, TQ showed superior inhibitory effects on iNOS and TGF-beta1. Meanwhile, CMN was more potent in inhibiting mRNA expression of TNF-alpha. These results suggest that TQ is more potent in inhibiting the inflammatory changes associating asthma. On the other hand, CMN was a less potent inhibitor of all measured parameters, despite its superior inhibitory effect on TNF-alpha mRNA levels. PMID- 22051976 TI - Distribution of organochlorine pesticides (OCs) and polychlorinated biphenyls (PCBs) in marine sediments directly exposed to wastewater from Cortiou, Marseille. AB - INTRODUCTION: The future 'Calanque National Park' coastlines of the Bouches-du Rhone and Var departments in France, constitute one of the ten biodiversity hot spots identified in the Mediterranean basin that receives industrial and urban wastewaters discharged from Marseille and its suburbs. MATERIALS AND METHODS: Organochlorine pesticides (OCs) and polychlorinated biphenyls (PCBs) were measured in sediments collected from 12 sampling sites (C1-C12) of sewage discharge to the sea from the wastewater treatment plant of Cortiou-Marseille. This study aims to determine the extent of these compounds in the sediments and to establish the possible sources of these contaminants. RESULTS AND DISCUSSION: Total pesticides in the sediments ranged from 1.2 to 190.6 ng g(-1) dry weight of sediment. The highest value was found at station C1, with a decreasing trend in total OC concentrations seaward. Among these compounds, the concentrations of the sum of dichlorodiphenyltrichloroethane (SigmaDDT) were the highest, ranging from 0.7 to 114.3 ng g(-1). PCB concentrations, expressed as equivalent to Arochlor 1260, varied from 9.1 to 226.9 ng g(-1). Individually, the dominant coplanar PCB congeners CB-153, CB-138 and CB-101. Generally, PCB concentrations at stations C2, C3, C5 and C7 were higher than those at stations C10, C11 and C12. Through some pollution indices, we showed the long-term contamination input of these OCs (DDT, endosulfan, HCH and heptachlor cases) rather than a recent release resulting from degradation and long-term weathering (dieldrin, aldrin and methoxychlor cases). Occurrence of PCBs might be due to their resistance to degradation processes or/and chronic inputs. CONCLUSIONS: By comparison with available sediment quality guideline (SQG) values, the environmental significance and toxicological implications of PCBs and OCs (i) reveal the probable adverse effects for the sediments from C1, C5, C6, C9 and (ii) confirm the adverse effect for marine biota and more particularly for benthic communities at C2-C4, C7 and C8. PMID- 22051977 TI - Physician self-referral and physician-owned specialty facilities. AB - Physician self-referral ranges from suggesting a follow-up appointment, to sending a patient to a facility in which the doctor has an ownership interest or financial relationship. Physician referral to facilities in which the physicians have an ownership interest is becoming increasingly common and not always medically appropriate. This Synthesis reviews the evidence on physician self referral arrangements, their effect on costs and utilization, and their effect on general hospitals. Key findings include: the rise in self-referral is sparked by financial, regulatory and clinical incentives, including patient convenience and doctors trying to preserve their income in the changing health care landscape. Strong evidence suggests self-referral leads to increased usage of health care services; but there is insufficient evidence to determine whether this increased usage reflects doctors meeting an unmet need or ordering clinically inappropriate care. The more significant a physician's financial interest in a facility, the more likely the doctor is to refer patients there. Arrangements through which doctors receive fees for patient referrals to third-party centers, such as "pay per-click," time-share, and leasing arrangements, do not seem to offer benefits beyond increasing physician income. So far, the profit margins of general hospitals have not been harmed by the rise in doctor-owned facilities. PMID- 22051978 TI - Multi-component, regio-selective aldol addition of beta-ketoesters to aldehydes: scope and applications. AB - Simple and effective multi-component one-pot aldol addition/protection reactions of beta-ketoesters to a series of aldehydes in the presence Me(3)SiCl and i Pr(2)EtN have been described. The analysis of the scope of the reaction revealed a dramatic dependence of the reactivity on the substrates used. Thus the effect of a catalytic amount of DMF and different reaction conditions was widely investigated. Further transformations of the aldol adducts were particularly useful to give valuable diols and compounds with quaternary stereocenters, while X-ray structural analysis gave also important stereochemical information about this challenging reaction. PMID- 22051979 TI - Paeoniflorin modulates multidrug resistance of a human gastric cancer cell line via the inhibition of NF-kappaB activation. AB - Research into the evasion of drug resistance and adverse effects is highly significant and urgent in the clinic. Therefore, accumulating studies have focused on the development of novel target-specific molecules related to drug resistance, and the establishment of rational therapeutic approaches. Currently, studies have shown that NF-kappaB activation may play an essential role in the development of chemotherapy resistance in carcinoma cells. Paeoniflorin, a principal bioactive component of the root of Paeonia lactiflora Pall., has been reported to exhibit various pharmacological effects. In the present study, we reported for the first time that paeoniflorin at non-toxic concentrations may effectively modulate multidrug resistance (MDR) of the human gastric cancer cell line SGC7901/vincristine (VCR) via the inhibition of NF-kappaB activation and, at least partly, by subsequently downregulating its target genes MDR1, BCL-XL and BCL-2. PMID- 22051980 TI - Fluorescent studies of salicylaldehyde and other related carbonyl compounds for the selective and sensitive detection of zinc(II) ions in aqueous solution. AB - Salicylaldehyde was found to have a high selectivity for zinc ions with simultaneous enhancement of fluorescence in aqueous buffer solution at optimum pH 8.5. The stoichiometry of the complex was determined to be 1:1 with a K(a) value of 3.4 * 10(4) M(-1) at 298 K. The fluorescence of the complex is not affected by common anions and Zn(2+) binds preferentially to salicylaldehyde in the presence of alkali, alkaline earth and heavy metal cations (Hg(2+), Cd(2+), Cr(3+) and Ni(2+)). This property is not observed with related phenolic compounds bearing a carbonyl group such as esters, amides, carboxylic acids and ketones. PMID- 22051981 TI - Interaction of CdTe quantum dots with 2,2-diphenyl-1-picrylhydrazyl free radical: a spectroscopic, fluorimetric and kinetic study. AB - The interaction of 2,2-diphenyl-1-picrylhydrazyl (DPPH(.) free radical with thiol capped CdTe quantum dots (QDs) has been studied by UV-vis spectroscopy, steady state and time resolved fluorescence measurements. Addition of DPPH(.) radical to CdTe QDs resulted in fluorescence quenching. The interaction occurs through static quenching as this was confirmed by fluorescence lifetime measurements. Time course absorption studies indicates that DPPH(.) may be reduced by interaction with QDs to the substituted hydrazine form (2,2-diphenyl-1 picrylhydrazine) DPPH-H. The mechanism of fluorescence quenching of CdTe QDs by DPPH(.) is proposed. PMID- 22051982 TI - A new fluorescent sensor for the determination of iron(III) in semi-aqueous solution. AB - A simple fluorescent sensor 1 has been developed for the recognition of Fe(III) in semi-aqueous solution at pH 7.0. The sensor, containing two Schiff base type receptors directly connected to naphthalene fluorophores, shows a concentration dependent decrease in emission intensity upon Fe(III) addition. The sensor was selective for Fe(III) over other metal ions and can measure Fe(III) ion concentration between 0.05 and 0.12 mM. The binding stoichiometry was established as 1:1 (host: guest) with a binding constant (Logbeta) of 4.01. Furthermore, the addition of Fe(III) to a solution of 1 caused a colour change from light yellow to colourless meaning 1 is also capable of detecting Fe(III) by the naked eye. PMID- 22051984 TI - Evidence-informed physical activity guidelines for people with spinal cord injury. PMID- 22051983 TI - Water deficit and salt stress diagnosis through LED induced chlorophyll fluorescence analysis in Jatropha curcas L. AB - LED induced chlorophyll fluorescence analysis is employed to investigate the effect of water deficit and salt stress upon the growth process of Jatropha curcas L.. Red(Fr) and far-red(FFr) chlorophyll fluorescence around 685 nm and 735 nm, respectively, were observed and examined as a function of the stress intensity(salt concentration and water deficit). The fluorescence ratio Fr/FFr which is a valuable nondestructive and nonintrusive indicator of the chlorophyll content of leaves was exploited to monitor the jatropha plants under stress. The data indicated that salinity plays a minor role in the chlorophyll concentration of leaves for NaCl concentrations in the 25 to 200 mM range. The fluorescence ratio also permitted the detection of damage caused by water deficit in the early stages of the plants growing process. A significant variation of the Fr/FFr ratio was observed in the first 10 days of the experiment, and before signs of visual stress became apparent. The results suggest that the Fr/FFr ratio is an early warning indicator of water deficit stress. PMID- 22051985 TI - Asymptomatic carotid stenosis in patients with intermittent claudication: epidemiological study. AB - AIM: The aim of this paper was to determine the prevalence of extracraneal carotid artery disease in patients with intermittent claudication, to describe classic cardiovascular risk factors in those with hemodynamically significant stenosis and to try to define subgroups at high risk, improving therefore the performance of non invasive testing. METHODS: A prospective descriptive study was conducted, with 146 patients reporting an intermittent claudication of the lower limbs and without a previous cerebrovascular event or carotid surgery. An ultrasonography examination was done. Risk factors were registed (smoking, dislipemia, arterial hypertension, diabetes mellitus), also ischemic cardiopathy and myocardial revascularization procedures. Univariate and multivariate analysis was made to define the variables associated with hemodynamically significant stenosis. RESULTS: Prevalence of hemodynamically significant stenosis was 23.2%. Smoking, dislipemia, arterial hypertension and diabetes mellitus were not significantly associated with carotid stenosis; 24.2% of patients affected of ischemic cardiopathy present a severe stenosis, and myocardial revascularization was a risk factor for carotid stenosis. CONCLUSION: Patients with claudication and ischemic miocardiopathy, especially when myocardial revascularization is needed, must be explored with carotid ultrasonography. In this patients, probably of hemodynamically significant carotid stenosis that requires treatment is more frequent. PMID- 22051986 TI - Endovascular abdominal aortic aneurysm repair: methods of radiological risk reduction. AB - AIM: The management of abdominal aortic aneurysm with endovascular repair (EVAR) requires extended exposure to ionizing radiation, before, during and after the intervention. The aim of this study was to quantify the radiological risks to patients and operating team, and to develop strategies to assess and reduce them. METHODS: EVAR was carried out in 97 patients using either a low-power mobile or a high-power stationary fluoroscopic unit. Empirically determined relationships between the indicated dose area product (DAP) and peak skin dose, obtained by direct in vivo dosimetry in a subgroup of patients, were used to predict the peak skin dose. Individual worker monitoring was used to assess personnel radiological burden. RESULTS: The probability for radiation induced biological effects due to the repair itself and the preoperative and life-long surveillance, as carried out, was about 2.4 10-3. The peak skin dose of repairs was linearly correlated with the DAP and did not exceed 1.2 Gy. The collective effective dose of the staff that carried out repairs using the mobile unit was 5.5 and 8 MUSv per repair using an angiographic and a surgical table, respectively. The use of the high-power fluoroscopic unit resulted in a many fold higher radiation burden to both patient and personnel. CONCLUSION: The optimum strategy, including equipment related factors, procedure-conduct factors and follow-up procedures, has to be studied, justified and optimized in each medical facility. PMID- 22051987 TI - Carotid stents: which is the best option? AB - Nowadays, carotid artery stenting (CAS) offers a potential alternative to carotid endarterectomy (CEA). CAS main advantages over CEA are the less invasive approach and the almost equal performance to CEA in terms of stroke prevention and complications. One of the most important factors which played significant role to CAS evolution is the progress in design of modern materials, especially stents. Today, several types of dedicated carotid stents have specific mechanical properties, which provide stents with individual characteristics making each of them suitable for specific carotid lesions and anatomies. The present review analyses the specific design and construction of modern stents, trying to point out their particular mechanical properties and characteristics. Additionally, it presents all available data published on comparison between different stent designs with the intention to identify which carotid stent is the best option for particular patient and lesion characteristics. PMID- 22051988 TI - Imaging for carotid stenting. AB - Carotid artery stenting (CAS) using embolic protection devices (EPD) has emerged as a viable alternative to carotid endarterectomy (CEA) in select patients. Imaging plays a critical role in the selection of patients for CAS. Duplex ultrasonography alone is insufficient to assess patients for CAS suitability. Advancements in computed tomography angiography (CTA) and magnetic resonance angiography (MRA) techniques are helping to identify lesions vulnerable to cerebral embolization during carotid interventions - a more prevalent event during CAS in comparison to CEA. Here we review the relevant data on the various imaging techniques available to improve patient selection and minimize neurologic adverse events during carotid artery stenting. PMID- 22051989 TI - Medical treatment in carotid artery intervention. AB - Medical treatment has a pivotal role in the treatment of patients with occlusive carotid artery disease. Large trials have provided the justification for operative treatment besides medical treatment in patients with recent significant carotid artery stenosis two decades ago. Since then, medical therapy has evolved tremendously. Next to aspirin, antiplatelet regimens acting on a different level in the modulation of platelet aggregation have made their entry. Moreover, statin therapy has been introduced. These changes among others in secondary stroke prevention, along with better understanding in life-style adjustments and perioperative medical management, have led to a decrease in stroke recurrence. Secondary prevention is therefore now the most important pillar of medical therapy. It consists of antiplatelet therapy, statins and blood pressure lowering agents in all patients. Small adjustments are recommended for those patients referred for invasive treatment. Moreover, long-term medical treatment is imperative. In this article, we summarize current evidence in literature regarding medical management in patients with previous stroke or TIA. PMID- 22051990 TI - New embolic protection devices: a review. AB - The use of embolic protection (EPD) during carotid artery stenting (CAS) has always made intuitive sense. There is no randomized trial evidence in favour of the use of EPDs and this results from the statistical challenge posed when attempting to compare variations in technique based on the outcome measure all stroke/death/myocardial infarction (MI) for a procedure such as CAS which, in experienced units, is associated with such a low baseline hazard. In order to detect a statistically meaningful difference between protected and unprotected populations, many thousands of patents would have to be recruited and this would entail a concerted effort amongst a population of physicians who are largely beyond uncertainty or equipoise regarding this particular issue. Accepting this, each type of device has been shown to capture macroemboli, implying, irrefutably, an added level of protection for the brain during CAS when EPDs are employed. Since their inception early in the last decade, the stenting community has been aware of the limitations of each type of system and accordingly, necessity has driven invention. This review seeks to present data on the newest EPDs, the philosophy behind them, their unique advantages, clinical data supporting their use and data highlighting the influence of these newer systems on the microembolic penalty of CAS, where available. PMID- 22051991 TI - A review of the main trials and registries: what we think we do and do not know about carotid artery stenting. AB - Despite many randomised controlled trials there are none that recommend carotid artery stenting (CAS) replaces carotid endarterectomy (CEA) for preventing stroke in patients with atherosclerotic carotid artery stenosis. CAS continues to be attractive due to its minimally-invasive nature and potential benefit in those patients at 'high risk' during open surgery. The belief that CAS will replace CEA is likely misplaced; a complimentary role for each mode of treatment is a more realistic vision for the future. Assessment of the existing data may provide useful information as to the subgroups that have most to benefit from each treatment type, therefore allowing a patient-specific approach to the management of individual lesions. This knowledge, coupled with further advances in the techniques of open and endovascular surgery, will progress the application of CAS and better its results. PMID- 22051992 TI - How to manage complications in CAS? AB - The different types of complications which might occur during CAS are described. Recommendations are given how to avoid and how to handle complications. PMID- 22051993 TI - Stroke and pulmonary embolism following manual and bandage compression after bleeding from a common femoral artery access site. AB - Manual compression (MC) is required to seal a common femoral artery (CFA) access site after endovascular intervention unless a mechanical closure device is used. Herein we report previously unpublished complications following MC of a CFA access site: stroke (embolism through a patent foramen ovale) and pulmonary embolism. These were a T thrombosis of the internal carotid artery combined with multi pulmonary embolisms and a case of pulmonary embolism. No thrombophilic conditions or other possible causes of venous emboli could be demonstrated in either case by laboratory tests or color-Duplex ultrasound. These were the only two cases of pulmonary and cerebral embolism seen at our university tertiary referral center, over a five-year period. This short report considers the potential risk factors as well as a prevention policy for these complications. PMID- 22051994 TI - First clinical use of a novel neurovascular access and neuroprotection system demonstrates complete absence of emboli by transcranial Doppler during carotid artery stenting. AB - This article focuses on the first use of the MICHITM Neuroprotection System in a transcervical carotid artery stenting procedure. The patient presented with an asymptomatic, 80% stenosis of the right internal carotid artery extending into the common carotid artery. The lesion was successfully treated with transcervical carotid access and reverse flow embolic protection and the successful placement of a carotid stent followed by balloon post-dilatation. Transcranial Doppler monitoring was performed throughout the procedure and a total of two micro embolic signals were recorded over the 30 minute procedural period. There were no neurologic complications reported during the 30-day follow-up period. PMID- 22051995 TI - Risk stratification of coronary revascularization patients by using clinical and angiographic data. AB - AIM: Patients undergoing coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) are still at a substantial risk of death after their procedures. A core group of preoperative and preprocedural risk factors and conditions contributes the majority of inherent mid- and long-term mortality risk in these patients. Therefore, we sought to develop a classification tree model as a practical and user-friendly method of predicting mid-term survival after coronary revascularization procedures. METHODS: We retrospectively analyzed data from a single, large-volume institution. Specifically, we examined all-cause three-year mortality in 3387 consecutive patients with multivessel or single proximal left anterior descending coronary artery disease who underwent either PCI with stenting or CABG. RESULTS: Recursive partitioning indicated that the best single predictor of death within three years was a history of heart failure (HF), followed by a proximal left circumflex artery (pLCX) lesion and age greater than 65 years for patients with and without a history of HF, respectively. With these variables, patients were readily stratified into low-, intermediate-, and high-risk groups whose risks of death over three years ranged from 2.3% to 36.2%. Among patients with a history of HF, pLCX stenosis was an independent predictor of mid-term mortality after adjustment for other known risk factors (hazard ratio, 1.46; 95% CI, 1.04-2.03). CONCLUSION: The constructed risk stratification scheme stratified patients into groups at low, intermediate, and high risk of death within three years. Stenosis of the pLCX seems to be an important prognostic factor for patients with a history of HF. PMID- 22051996 TI - Hypertension in adult after operation of aortic coarctation. AB - AIM: The benefit of coarctation repair on the resolution of systolic hypertension in adults has been questioned. METHODS: Between March 1997 and July 2009, 65 consecutive adult patients (>= 16 years) underwent repair of aortic coarctation. There were 40 men (65%) and 25 women (35%) with a mean age of 22.3 +/- 4.8 years (range, 16 to 34 years). All patients had critical systolic blood hypertension (SBP >= 140 mmHg). SBP ranged from 140 to 205 mmHg, with a mean of 163.5 +/- 17.6 mmHg. The mean diastolic BP was 95.1 +/- 18.3 mmHg (range, 70 to 120 mmHg). Most patients (41/65, 74%) were on a regimen of at least one antihypertensive drug. RESULTS: The patients were followed up after coarctation repair for 2 to 144 months (mean, 68 +/- 39 months). There was no death. No other major complications occurred. There have been no repeat interventions during follow-up. Four patients were lost to follow-up. Of the 61 patients with preoperative hypertension, 53 (87%) were normotensive (SBP <140 mmHg) at the most recent follow-up visit. The remaining eight patients showed substantial improvement versus the preoperative status. The mean SBP after operation was 122.5 +/- 12.4 mmHg. Mean diastolic blood pressure was 79.5 +/- 11.6 mmHg. Forty-one (67%) patients were taking no medication at the last follow-up. CONCLUSION: Surgical repair of coarctation of the aorta in adults can lead to regression of systolic hypertension and a decreased requirement for antihypertensive medication. PMID- 22051997 TI - Relative importance of patient, procedural and anatomic risk factors for early vein graft thrombosis after coronary artery bypass graft surgery. AB - AIM: The aim of the present study was to investigate the relative importance of a wide array of patient demographic, procedural, anatomic and perioperative variables as potential risk factors for early saphenous vein graft (SVG) thrombosis after coronary artery bypass graft (CABG) surgery. METHODS: The patency of 611 SVGs in 291 patients operated on at four different hospitals enrolled in the Reduction in Graft Occlusion Rates (RIGOR) study was assessed six months after CABG surgery by multidetector computed tomography coronary angiography or clinically-indicated coronary angiography. The odds of graft occlusion versus patency were analyzed using multilevel multivariate logistic regression with clustering on patient. RESULTS: SVG failure within six months of CABG surgery was predominantly an all-or-none phenomenon with 126 (20.1%) SVGs totally occluded, 485 (77.3%) widely patent and only 16 (2.5%) containing high grade stenoses. Target vessel diameter <= 1.5 mm (adjusted OR 2.37, P=0.003) and female gender (adjusted OR 2.46, P=0.01) were strongly associated with early SVG occlusion. In a subgroup analysis of 354 SVGs in which intraoperative graft blood flow was measured, lower mean flow was also significantly associated with SVG occlusion when analyzed as a continuous variable (adjusted OR 0.984, P=0.006) though not when analyzed dichotomously, <40 mL/min versus >= 40 mL/min (adjusted OR 1.86, P=0.08). CONCLUSION: Small target vessel diameter, female gender and low mean graft blood flow are significant risk factors for SVG thrombosis within six months of CABG surgery in patients on postoperative aspirin therapy. This information may be useful in guiding revascularization strategies in selected patients. PMID- 22051998 TI - Gender-related differences in patients undergoing mechanical aortic valve replacement with the CarboMedics valve. AB - AIM: The aim of this paper was to evaluate gender-related differences in patients undergoing mechanical aortic valve replacement with the CarboMedics valve. METHODS: During a 20 year period, 629 patients (median age 60 years) underwent mechanical aortic valve replacement with the CarboMedics valve. Of these, 215 patients were female (34%). The median follow-up for the entire cohort was 10.2 +/- 6.2 years. RESULTS: In-hospital mortality for the entire cohort was 9% (male 7.3% vs. female 11.0%, P=0.005). Cox regression analysis revealed redo-surgery (HR=2.35, CI 1.35-4.08), LVEF<30% (HR=2.31, CI 1.36-3.93), age (HR=1.60, CI 1.27 2.02), as well as female gender (HR=2.07, CI 1.28-3.35) as independent predictors of survival. For male gender LVEF<30% (HR=2.47, CI 1.23-4.93) and age (HR=1.75, CI 1.25-2.43) were independent predictors of survival. For female gender, additional CABG (HR=2.15, CI 1.08-4.28), redo surgery (HR=3.64, CI 1.78-7.46) as well as age (HR=1.48, CI 1.06-2.06) were independent predictors of survival. CONCLUSION: Gender per se is an independent risk factor of survival after mechanical aortic valve replacement. Severely impaired LVEF independently predicts survival in males whereas additional CABG and redo surgery do in females. Age affects survival in both sexes. These findings may serve as a basis for further improving gender related outcome. PMID- 22051999 TI - Surgical thromboembolectomy for a massive pulmonary embolism after several venous thromboembolic episodes caused by congenital antithrombin III deficiency. PMID- 22052002 TI - Mathematical model of biological order state or syndrome in traditional Chinese medicine: based on electromagnetic radiation within the human body. AB - In this study, based on the resonator model and exciplex model of electromagnetic radiation within the human body, mathematical model of biological order state, also referred to as syndrome in traditional Chinese medicine, was established and expressed as: "Sy = v/ 1n(6I + 1)". This model provides the theoretical foundation for experimental research addressing the order state of living system, especially the quantitative research syndrome in traditional Chinese medicine. PMID- 22052001 TI - Treating cutis verticis gyrata using skin expansion method. AB - The objective of this study was to evaluate the feasibility and clinical effect of repairing scalp defect after the excision of cutis verticis gyrata using expanded scalp skin flaps. For this purpose, 8 patients with cutis verticis gyrata were subjected to scalp skin expander implantation under the skin. After saline injection and scalp expansion for 2-3 months, the cutis verticis gyrata was excised and the expanded scalp flaps were applied to recover the skin defect. As a result, the flaps and hair grew well without contractures and significant scarring, suggesting that this method is useful for surgical correction of cutis verticis gyrata. PMID- 22052003 TI - Survivin siRNA inhibits gastric cancer in nude mice. AB - The objective of the study was to evaluate the expression of survivin, cell proliferation, and apoptosis in survivin-specific siRNA-transfected human gastric cancer cell line MGC-803. For this purpose, the target gene fragments were cloned into pSilencer3.1-Hl neo vector. Recombinant eukaryotic expression vector, pSilencer3.1-SVV was successfully constructed and then the recombinant vector was transfected into gastric cancer MGC-803 cells. The mRNA expression of survivin was determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Survivin protein expression was detected by Western blot. Cell cycle distribution and apoptosis were determined by flow cytometry. Our data regarding RT-PCR and Western blot showed that pSilencer3.1-SVV vector could knockdown the expression of survivin mRNA and protein. In contrast with the control group, the apoptotic index of MGC-803 cells increased remarkably. Survivin-specific siRNA caused cells accumulation in the G2/M phase and the number of cells in the G0/G1 phase decreased after transfection. It was, therefore, concluded that the siRNA targeting survivin gene could inhibit the proliferation of gastric cancer cells and induce apoptosis. The use of survivin siRNA may provide a novel approach for gene therapy of gastric cancer. PMID- 22052004 TI - A genome-wide association study of osteochondritis dissecans in the Thoroughbred. AB - Osteochondrosis is a developmental orthopaedic disease that occurs in horses, other livestock species, companion animal species, and humans. The principal aim of this study was to identify quantitative trait loci (QTL) associated with osteochondritis dissecans (OCD) in the Thoroughbred using a genome-wide association study. A secondary objective was to test the effect of previously identified QTL in the current population. Over 300 horses, classified as cases or controls according to clinical findings, were genotyped for the Illumina Equine SNP50 BeadChip. An animal model was first implemented in order to adjust each horse's phenotypic status for average relatedness among horses and other potentially confounding factors which were present in the data. The genome-wide association test was then conducted on the residuals from the animal model. A single SNP on chromosome 3 was found to be associated with OCD at a genome-wide level of significance, as determined by permutation. According to the current sequence annotation, the SNP is located in an intergenic region of the genome. The effects of 24 SNPs, representing QTL previously identified in a sample of Hanoverian Warmblood horses, were tested directly in the animal model. When fitted alongside the significant SNP on ECA3, two of these SNPs were found to be associated with OCD. Confirmation of the putative QTL identified on ECA3 requires validation in an independent sample. The results of this study suggest that a significant challenge faced by equine researchers is the generation of sufficiently large data sets to effectively study complex diseases such as osteochondrosis. PMID- 22052000 TI - Growing skin: tissue expansion in pediatric forehead reconstruction. AB - Tissue expansion is a common surgical procedure to grow extra skin through controlled mechanical over-stretch. It creates skin that matches the color, texture, and thickness of the surrounding tissue, while minimizing scars and risk of rejection. Despite intense research in tissue expansion and skin growth, there is a clear knowledge gap between heuristic observation and mechanistic understanding of the key phenomena that drive the growth process. Here, we show that a continuum mechanics approach, embedded in a custom-designed finite element model, informed by medical imaging, provides valuable insight into the biomechanics of skin growth. In particular, we model skin growth using the concept of an incompatible growth configuration. We characterize its evolution in time using a second-order growth tensor parameterized in terms of a scalar-valued internal variable, the in-plane area growth. When stretched beyond the physiological level, new skin is created, and the in-plane area growth increases. For the first time, we simulate tissue expansion on a patient-specific geometric model, and predict stress, strain, and area gain at three expanded locations in a pediatric skull: in the scalp, in the forehead, and in the cheek. Our results may help the surgeon to prevent tissue over-stretch and make informed decisions about expander geometry, size, placement, and inflation. We anticipate our study to open new avenues in reconstructive surgery and enhance treatment for patients with birth defects, burn injuries, or breast tumor removal. PMID- 22052005 TI - Inherited liver shunts in dogs elucidate pathways regulating embryonic development and clinical disorders of the portal vein. AB - Congenital disorders of the hepatic portal vasculature are rare in man but occur frequently in certain dog breeds. In dogs, there are two main subtypes: intrahepatic portosystemic shunts, which are considered to stem from defective closure of the embryonic ductus venosus, and extrahepatic shunts, which connect the splanchnic vascular system with the vena cava or vena azygos. Both subtypes result in nearly complete bypass of the liver by the portal blood flow. In both subtypes the development of the smaller branches of the portal vein tree in the liver is impaired and terminal branches delivering portal blood to the liver lobules are often lacking. The clinical signs are due to poor liver growth, development, and function. Patency of the ductus venosus seems to be a digenic trait in Irish wolfhounds, whereas Cairn terriers with extrahepatic portosystemic shunts display a more complex inheritance. The genes involved in these disorders cannot be identified with the sporadic human cases, but in dogs, the genome-wide study of the extrahepatic form is at an advanced stage. The canine disease may lead to the identification of novel genes and pathways cooperating in growth and development of the hepatic portal vein tree. The same pathways likely regulate the development of the vascular system of regenerating livers during liver diseases such as hepatitis and cirrhosis. Therefore, the identification of these molecular pathways may provide a basis for future proregenerative intervention. PMID- 22052006 TI - Establishment of ES cells from inbred strain mice by dual inhibition (2i). AB - A number of mouse ES cells from inbred strains have been established to date, but efficiency varies across the different strains. The 129 strain mouse is efficient to establish, whereas C57BL/6 and BALB/c strains are not. It is possible that their genetic backgrounds account for the difference in their ability to establish ES cell lines. In this study, we attempted to establish C57BL/6J and BALB/c Cr ES cells by dual inhibition (2i) using two inhibitors (PD0325901 and CHIR99021) of extracellular signal regulated-kinase (ERK) and glycogen synthase kinase-3 (GSK-3), which promote ES cell differentiation. The results revealed that the establishment efficiencies of C57BL/6J and BALB/c Cr ES cells were remarkably increased by 2i. These ES cells stably expressed pluripotent markers and generated high-contribution chimeras with germline transmission. Furthermore, we generated germline chimeras from C57BL/6J ES cells through the method of gene modification. These findings indicate that 2i is a powerful tool for establishing C57BL/6J and BALB/c Cr ES cells with the ability to generate germline chimeras. PMID- 22052007 TI - Upregulation of interferon-stimulated genes and interleukin-10 in peripheral blood immune cells during early pregnancy in dairy cows. AB - In cows, interferon-tau (IFNT) regulates maternal recognition around days 15-19 after artificial insemination (AI). The present study hypothesized that if key target genes of IFNT are clearly upregulated in earlier stages of pregnancy, these genes could be use as indices of future pregnancy in cows. Therefore, we determined the expression of these genes in peripheral blood mononuclear leukocytes (PBMCs) and polymorphonuclear granulocytes (PMNs) during the maternal recognition period (MRP). Twenty multiparous Holstein cows were subjected to AI on day 0 and categorized into the following groups: pregnancy (Preg, n = 9), embryonic death (ED, n = 5) and non-pregnancy (NP, n = 6). Progesterone levels in the Preg group were higher than those in the NP group on days 12-21. ISG15 and OAS-1 (IFN-stimulated genes: ISGs) mRNA in PBMCs on day 8 was higher in the Preg group than in the NP group, and these mRNAs in PMNs was higher in the Preg group on day 5 than in the NP and ED groups. Interleukin-10 (IL-10, Th2 cytokine) mRNA expression increased on day 8 in the PBMCs of pregnant cows. Tumor necrosis factor alpha (TNFalpha, Th1 cytokine) mRNA expression was stable in all groups. In an in vitro cell culture experiment, IFNT stimulated mRNA expression of ISGs in both PBMCs and PMNs. IFNT stimulated IL-10 mRNA expression in PBMCs, whereas IFNT increased TNFalpha mRNA levels in PBMCs in vitro. The results suggest that ISGs and IL-10 could be responsive to IFNT before the MRP in peripheral blood immune cells and may be useful target genes for reliable indices of pregnancy before the MRP. PMID- 22052008 TI - Importance of methionine metabolism in morula-to-blastocyst transition in bovine preimplantation embryos. AB - The roles of methionine metabolism in bovine preimplantation embryo development were investigated by using ethionine, an antimetabolite of methionine. In vitro produced bovine embryos that had developed to the 5-cell stage or more at 72 h after the commencement of in vitro fertilization (IVF) were then cultured until day 8 (IVF = day 0) in medium supplemented with 0 (control), 1, 5 and 10 mM ethionine. Compared with the blastocyst development in the control (40.0%), ethionine at 10 mM almost completely blocked blastocyst development (1.1%, P<0.001), and this concentration was used in the following experiments. Methionine added at the same concentration (10 mM, a concentration control of ethionine) did not cause such an intense developmental inhibition. Development to the compacted morula stage on day 6 was not affected by 10 mM ethionine treatment. S-adenosylmethionine (SAM) added to the ethionine treatment partly restored the blastocyst development. Semiquantitative reverse transcription polymerase chain reaction analysis of cell lineage-related transcription factors in day 6 compacted morulae showed that the expressions of NANOG and TEAD4 were increased by ethionine treatment relative to the control (P<0.01). Furthermore, immunofluorescence analysis of 5-methylcytosine revealed that DNA was hypomethylated in the ethionine-treated day 6 morulae compared with the control (P<0.001). These results demonstrate that the disruption of methionine metabolism causes impairment of the morula-to-blastocyst transition during bovine preimplantation development in part via SAM deficiency, indicating the indispensable roles of methionine during this period. The disruption of methionine metabolism may cause hypomethylation of DNA and consequently lead to the altered expression of developmentally important genes, which then results in the impairment of blastocyst development. PMID- 22052009 TI - Anti-Mullerian hormone profiles as a novel biomarker to diagnose granulosa-theca cell tumors in cattle. AB - This study was carried out to evaluate the blood profile and tissue expression of Anti-Mullerian hormone (AMH) as a biomarker for granulosa-theca cell tumors (GTCTs) in cattle. Five cases with unilateral ovarian GTCTs (GTCT group) were investigated in comparison to other groups of Japanese Black cows, which had either cystic ovarian disease (COD group, n=5), a functional corpus luteum on Days 9 to 11 of the estrous cycle (Day 0=estrus; CL group, n=13) or received superovulation treatment (SOT group, n=13). We used transrectal ultrasonography and measured plasma AMH, estradiol-17beta (E(2)), progesterone (P(4)) and testosterone (T) levels. Moreover, GTCT tissues were collected and examined by immunohistochemical staining (IHC) for AMH. In the GTCT group, ultrasound images of GTCTs were variable and not definitive. However, the AMH level in the GTCT group (n=3, 58.1 +/- 66.3 ng/ml) was significantly higher than in the COD, CL and SOT groups (0.1 +/- 0.1 ng/ml for GTCT vs. COD, P<0.05; 0.2 +/- 0.1 and 0.3 +/- 0.2 ng/ml, respectively for GTCT vs. CL and SOT, P<0.01). The other hormonal levels in the GTCT group had no significant differences compared with the COD or SOT group. Neoplastic granulosa cells labeled with AMH antibody clearly demonstrated a variety of tissue patterns in all cases by IHC. To the best of our knowledge, this is the first study to investigate the blood profile and IHC of AMH in bovine GTCTs. Our findings indicate that AMH may be a novel biomarker to diagnose GTCTs in cattle. PMID- 22052010 TI - Purification of N-acetyllactosamine-binding activity from the porcine sperm membrane: possible involvement of an ADAM complex in the carbohydrate-binding activity of sperm. AB - Although the importance of carbohydrate recognition by sperm during egg zona pellucida binding has been widely reported, the sperm molecular species that recognize the carbohydrates are poorly characterized. Our previous cytochemical study indicated that two kinds of carbohydrate-binding proteins are expressed on porcine sperm heads-one recognizes N-acetyllactosamine (Galbeta1-4GlcNAc-), and the other recognizes the Lewis X structure (Galbeta1-4(Fucalpha1-3)GlcNAc-). For this report, we used proteomic techniques to characterize the sperm proteins that bind N-acetyllactosamine. Porcine sperm plasma membrane was solubilized with a detergent solution and subjected to sequential chromatography with dextran sulfate agarose, affinity, and hydroxyapatite, and the binding activities in the eluates were monitored by a solid-phase binding assay. The tryptic peptides of two proteins most likely associated with the binding activities were subjected to tandem mass spectrometry sequencing. A subsequent database search identified one of the two proteins as predicted disintegrin and metalloprotease domain containing protein 20-like (XP_003128672). The other protein was identified as disintegrin and metalloprotease domain-containing protein 5 (AB613817) by database searches for homologous amino acid sequences, cDNA cloning, nucleotide sequencing and nucleotide database searches. Furthermore, two-dimensional blue native/SDS-PAGE demonstrated that they formed a variety of non-covalent complexes. Therefore, these ADAM complexes probably are responsible for the N acetyllactosamine-binding activity. An affinity-purified fraction containing these ADAM complexes showed zona pellucida-binding activity, though the activity was relatively weak, and the presence of another zona pellucida-binding protein that probably works in concert with these ADAM complexes was suggested. Immunofluorescence testing suggested that ADAM20-like was localized on the anterior part of the sperm plasma membrane. PMID- 22052011 TI - Effect of RNA interference of BID and BAX mRNAs on apoptosis in granulosa cell derived KGN cells. AB - In mitochondrion-dependent type II apoptosis, BH3-interacting domain death agonist (BID) and BCL-2-associated X protein (BAX) promote death ligand and receptor-mediated cell death. In porcine ovaries, the levels of BID and BAX increase in follicular granulosa cells during atresia. In the present study, to confirm the pro-apoptotic activity of BID and BAX in granulosa cells, we examined the effect of RNA interference of BID or BAX on apoptosis using a human ovarian granulosa tumor cell line, KGN. By reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, expression of BID and BAX was detected in KGN cells. Then, we suppressed BID and BAX mRNA expression in KGN cells using small interfering RNA (siRNA). When BID or BAX was suppressed, a significant decrease in the apoptotic cell rate was noted. In granulosa-derived cells, BID and BAX showed pro-apoptotic activity. These results suggest that BID and BAX act as signal-transducing factors in mitochondrion-dependent type II apoptosis. PMID- 22052012 TI - Differential involvement of amygdala corticosteroid receptors in visceral hyperalgesia following acute or repeated stress. AB - Symptoms of irritable bowel syndrome (IBS) are exacerbated by stress. Previously, we demonstrated that the stress hormone corticosterone applied directly to the amygdala induced visceral hypersensitivity through the actions of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). However, the involvement of amygdaloid GR and MR in the regulation of visceral sensitivity following psychological stress is unknown; therefore, the goal of the present study was to determine the relative importance of amygdaloid GR and MR in the regulation of visceral sensitivity in a rodent model of behavioral stress. Male F-344 rats were stereotaxically implanted with micropellets bilaterally on the dorsal margin of the amygdala containing the GR antagonist mifepristone, the MR antagonist spironolactone, or cholesterol as a control. Animals were then exposed to 1 h of water-avoidance stress (WAS) or sham stress for 1 day (acute) or 7 days (repeated). Visceral sensitivity was assessed either 1 h or 24 h after the final session of WAS and quantified as the number of contractions of the external abdominal oblique, a visceromotor response, in response to colorectal distension at pressures of 0-60 mmHg. Acute stress induced transient visceral hyperalgesia, which was absent 24 h after WAS and independent of GR and MR. Conversely, repeated WAS induced sustained visceral hyperalgesia that was abolished by specifically targeting the amygdala with GR and MR antagonists. These results demonstrate that the amygdala corticosteroid system plays an essential role in mediating the effects of repeated WAS on visceral sensitivity. Furthermore, our findings suggest that amygdaloid GR and MR may be involved in IBS symptomatology. PMID- 22052013 TI - Partial deletion of argininosuccinate synthase protects from pyrazole plus lipopolysaccharide-induced liver injury by decreasing nitrosative stress. AB - Argininosuccinate synthase (ASS) is the rate-limiting enzyme in the urea cycle. Along with nitric oxide synthase (NOS)-2, ASS endows cells with the L citrulline/nitric oxide (NO.) salvage pathway to continually supply L-arginine from L-citrulline for sustained NO. generation. Because of the relevant role of NOS in liver injury, we hypothesized that downregulation of ASS could decrease the availability of intracellular substrate for NO. synthesis by NOS-2 and, hence, decrease liver damage. Previous work demonstrated that pyrazole plus LPS caused significant liver injury involving NO. generation and formation of 3 nitrotyrosine protein adducts; thus, wild-type (WT) and Ass+/- mice (Ass+/+ mice are lethal) were treated with pyrazole plus LPS, and markers of nitrosative stress, as well as liver injury, were analyzed. Partial ablation of Ass protected from pyrazole plus LPS-induced liver injury by decreasing nitrosative stress and hepatic and circulating TNFalpha. Moreover, apoptosis was prevented, since pyrazole plus LPS-treated Ass+/- mice showed decreased phosphorylation of JNK; increased MAPK phosphatase-1, which is known to deactivate JNK signaling; and lower cleaved caspase-3 than treated WT mice, and this was accompanied by less TdT-mediated dUTP nick end labeling-positive staining. Lastly, hepatic neutrophil accumulation was almost absent in pyrazole plus LPS-treated Ass+/- compared with WT mice. Partial Ass ablation prevents pyrazole plus LPS-mediated liver injury by reducing nitrosative stress, TNFalpha, apoptosis, and neutrophil infiltration. PMID- 22052014 TI - PKCdelta-dependent activation of ERK1/2 leads to upregulation of the human NHE2 transcriptional activity in intestinal epithelial cell line C2BBe1. AB - The apical Na+/H+ exchanger (NHE) isoform NHE2 is involved in transepithelial Na+ absorption in the intestine. Our earlier studies have shown that mitogenic agent phorbol 12-myristate 13-acetate (PMA) induces the expression of NHE2 through activation of transcription factor early growth response-1 (Egr-1) and its interactions with the NHE2 promoter. However, the signaling pathways involved in transcriptional stimulation of NHE2 in response to PMA in the intestinal epithelial cells are not known. Chemical inhibitors and genetic approaches were used to investigate the signaling pathways responsible for the stimulation of NHE2 expression by PMA via Egr-1 induction. We show that, in response to PMA, PKCdelta, a member of novel PKC isozymes, and MEK-ERK1/2 pathway of mitogen activated protein kinases stimulate the NHE2 expression in C2BBe1 intestinal epithelial cells. PMA rapidly and transiently induced activation of PKCdelta. Small inhibitory RNA-mediated knockdown of PKCdelta blocked the stimulatory effect of PMA on the NHE2 promoter activity. In addition, blockade of PKCdelta by rottlerin, a PKCdelta-specific inhibitor, and ERK1/2 by U0126, a MEK-ERK inhibitor, abrogated PMA-induced Egr-1 expression. Immunofluorescence studies revealed that inhibition of ERK1/2 activation prevents translocation of PMA induced Egr-1 into the nucleus. Consistent with these data, PMA-induced Egr-1 interaction with the NHE2 promoter region was prevented in nuclear extracts from U0126-pretreated cells. In conclusion, our data provide the first evidence that the stimulatory effect of PMA on NHE2 expression is mediated through the initial activation of PKCdelta, subsequent PKCdelta-dependent activation of MEK-ERK1/2 signaling pathway, and stimulation of Egr-1 expression. Furthermore, we show that transcription factor Egr-1 acts as an intermediate effector molecule that links the upstream signaling cues to the long-term stimulation of NHE2 expression by PMA in C2BBe1 cells. PMID- 22052015 TI - Tumor necrosis factor receptor 1 functions as a tumor suppressor. AB - Tumor necrosis factor (TNF) is a key player in inflammatory bowel disease and has been variably associated with carcinogenesis, but details of the cross talk between inflammatory and tumorigenic pathways remain incompletely understood. It has been shown that, in C57BL/6 mice, signaling via TNF receptor 1 (TNFR1) is protective from injury and inflammation in experimental colitis. Therefore, we hypothesized that loss of TNFR1 signaling would confer increased risk of developing colitis-associated carcinoma. Using three models of murine tumorigenesis based on repeated bouts of inflammation or systemic tumor initiator, we sought to determine the roles of TNF and TNFR1 with regard to neoplastic transformation in the colon in wild-type (WT), TNFR1 knockout (R1KO), and TNF knockout (TNFKO) mice. We found R1KO animals to have more severe disease, as defined by weight loss, hematochezia, and histology. TNFKO mice demonstrated less weight loss but were consistently smaller, and rates and duration of hematochezia were comparable to WT mice. Histological inflammation scores were higher and neoplastic lesions occurred more frequently and earlier in R1KO mice. Apoptosis is not affected in R1KO mice although epithelial proliferation following injury is more ardent even before tumorigenesis is apparent. Lastly, there is earlier and more intense expression of activated beta-catenin in these mice, implying a connection between TNFR1 and Wnt signaling. Taken together, these findings show that in the context of colitis-associated carcinogenesis TNFR1 functions as a tumor suppressor, exerting this effect not via apoptosis but by modulating activation of beta-catenin and controlling epithelial proliferation. PMID- 22052017 TI - Pectin Methylesterase genes influence solid wood properties of Eucalyptus pilularis. AB - This association study of Eucalyptus pilularis populations provides empirical evidence for the role of Pectin Methylesterase (PME) in influencing solid wood characteristics of Eucalyptus. PME6 was primarily associated with the shrinkage and collapse of drying timber, which are phenotypic traits consistent with the role of pectin as a hydrophilic polysaccharide. PME7 was primarily associated with cellulose and pulp yield traits and had an inverse correlation with lignin content. Selection of specific alleles in these genes may be important for improving trees as sources of high-quality wood products. A heterozygote advantage was postulated for the PME7 loci and, in combination with haplotype blocks, may explain the absence of a homozygous class at all single-nucleotide polymorphisms investigated in this gene. PMID- 22052016 TI - Resveratrol causes cell cycle arrest, decreased collagen synthesis, and apoptosis in rat intestinal smooth muscle cells. AB - One of the most difficult and treatment-resistant complications of Crohn's disease is the development of fibrotic intestinal strictures due to mesenchymal cell hyperplasia and collagen deposition. Resveratrol, a phytoalexin found in berries, peanuts, grapes, and red wine, has been shown to inhibit fibrosis in vasculature, heart, lung, kidney, liver, and esophagus in animal models. Resveratrol has also been shown to inhibit oxidation, inflammation, and cell proliferation and to decrease collagen synthesis in several cell types or animal models. The aim of this study was to determine whether resveratrol has antifibrotic effects on intestinal smooth muscle cells. Responses to resveratrol by cultured smooth muscle cells isolated from colons of untreated Lewis rats were examined; this rat strain is used in a model of Crohn's disease with prominent intestinal fibrosis. A relative decrease in cell numbers following treatment with 50 and 100 MUM resveratrol was evident at 24 h (P <= 0.005). This effect was largely due to cell cycle arrest, with an increase in the percent of cells in S phase from 8 to 25-35% (P < 0.05). Cell viability was unchanged until 2-3 days of treatment when there was a 1.2- to 5.0-fold increase in the percent of apoptotic cells, depending on the assay (P < 0.05). Expression of collagen type I protein was decreased following treatment with resveratrol for 24 h (to 44 and 25% of control levels with 50 and 100 MUM resveratrol, respectively; P < 0.05). Expression of procollagen types I and III mRNA was also decreased with resveratrol treatment. Resveratrol (50 MUM) diminished the proliferative response to TGF-beta1 (P = 0.02) as well as IGF-I-stimulated collagen production (P = 0.02). Thus resveratrol decreases intestinal smooth muscle cell numbers through its effects on cell cycle arrest and apoptosis and also decreases collagen synthesis by the cells. These effects could be useful in preventing the smooth muscle cell hyperplasia and collagen deposition that characterize stricture formation in Crohn's disease. PMID- 22052018 TI - Influence of examiner experience on the reproducibility of retinal nerve fiber thickness values using Cirrus and Stratus OCTs. AB - PURPOSE: The purpose of the study was to evaluate the influence of the examiner's experience on the reproducibility of retinal nerve fiber layer (RNFL) measurements obtained with Cirrus optical coherence tomography (OCT) and Stratus. METHODS: Fifty-one normal and glaucomatous eyes of 51 participants were included. Two examiners (1 novice, 1 experienced) obtained 2 scans using both OCTs. For quantitative measurements, Bland and Altman limits of agreement were evaluated. For qualitative classifications, kappa coefficients were calculated. RESULTS: Signal strength was higher with Cirrus than with Stratus (P<0.05). Signal strength was higher in scans performed by the experienced examiner than in those carried out by the inexperienced examiner in Stratus but not in Cirrus. RNFL measurement differences between Cirrus and Stratus were influenced by the examiner for the inferior (P=0.02), superior (P<0.001), and temporal quadrants (P=0.009). The RNFL quantitative agreement of examiners was higher in Cirrus than in Stratus. The qualitative agreement (kappa coefficients) of both examiners in the RNFL classification were almost perfect with Cirrus (in the average, superior, and inferior quadrants), and moderate with Stratus (only in average and inferior quadrant). CONCLUSIONS: The signal strength is independent of the examiner's experience in Cirrus but not in Stratus. RNFL measurements obtained by both examiners were more reproducible with Cirrus than with Stratus. The differences in RNFL measurements between both OCTs were related to the examiner's experience in all 3 quadrants. Agreement between operators in the RNFL classification was higher with Cirrus than Stratus. PMID- 22052019 TI - Towards the adaptation of grapevine varieties to climate change: QTLs and candidate genes for developmental stages. AB - The genetic determinism of developmental stages in grapevine was studied in the progeny of a cross between grapevine cultivars Riesling and Gewurztraminer by combining ecophysiological modelling, genetic analysis and data mining of the grapevine whole genome sequence. The dates of three phenological stages, budbreak, flowering and veraison, were recorded during four successive years for 120 genotypes in the vineyard. The phenotypic data analysed were the duration of three periods expressed in thermal time (degree-days): 15 February to budbreak (Bud), budbreak to flowering (Flo) and flowering to veraison (Ver). Parental and consensus genetic maps were built using 153 microsatellite markers on 188 individuals. Six independent quantitative trait loci (QTLs) were detected for the three phases. They were located on chromosomes 4 and 19 for Bud, chromosomes 7 and 14 for Flo and chromosomes 16 and 18 for Ver. Interactions were detected between loci and also between alleles at the same locus. Using the available grapevine whole-genome sequences, candidate genes underlying the QTLs were identified. VvFT, on chromosome 7, and a CONSTANS-like gene, on chromosome 14, were found to colocalise with the QTLs for flowering time. Genes related to the abscisic acid response and to sugar metabolism were detected within the confidence intervals of QTLs for veraison time. Their possible roles in the developmental process are discussed. These results raise new hypotheses for a better understanding of the physiological processes governing grapevine phenology and provide a framework for breeding new varieties adapted to the future predicted climatic conditions. PMID- 22052020 TI - On the mechanisms of ionic conductivity in BaLiF3: a molecular dynamics study. AB - The mechanisms of ionic conductivity in BaLiF(3) are investigated using molecular simulations. Direct molecular dynamics simulations of (quasi) single crystalline super cell models hint at the preferred mobility mechanism which is based on fluoride interstitial (and to a smaller extent F(-) vacancy) migration. Analogous to previous modeling studies, the energy related to Frenkel defect formation in the ideal BaLiF(3) crystal was found as 4-5 eV which is in serious controversy to the experimentally observed activation barrier to ionic conductivity of only 1 eV. However, this controversy could be resolved by incorporating Ba(2+)<-> Li(+) exchange defects into the elsewise single crystalline model systems. Indeed, in the neighborhood of such cation exchange defects the F(-) Frenkel defect formation energy was identified to reduce to 1.3 eV whilst the cation exchange defect itself is related to a formation energy of 1.0 eV. Thus, our simulations hint at the importance of multiple defect scenarios for the ionic conductivity in BaLiF(3). PMID- 22052021 TI - Expression of alpha-crystallin in the retina of human sympathetic ophthalmia. AB - Sympathetic ophthalmia (SO) is a bilateral, granulomatous, intraocular inflammation that occurs following a penetrating injury to one eye, and has the potential to cause blindness of both eyes. The aim of this study was to examine the expression of alpha-crystallin and to detect apoptotic cells in the retina of human eyes with SO. Five globes, including three with SO and two age-matched normal appearing retinae, were examined. Formalin-fixed, paraffin-embedded tissue sections were submitted to hematoxylin and eosin staining and immuno histochemistry with anti-alphaA and alphaB-crystallin antibodies. Apoptotic cells were detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method, and double-staining immunohistochemistry was conducted together with the TUNEL reaction. In normal-appearing retina, alphaA-crystallin immunoreactivity was predominantly detected in the cytoplasm of photoreceptors, where alphaB-crystallin was less marked. In SO globes, granulomatous inflammation was noted in the choroid, whereas the retina and choriocapillaris were preserved. Immunoreactivity for alphaA-crystallin was detected in the retina, as well as in the cytoplasm and inner/outer photoreceptor segments. By contrast, alphaB crystallin was weakly noted in the SO retina. Double-staining immuno histochemistry revealed no TUNEL-positive photoreceptors in the retina displaying high immunoreactivity for alphaA-crystallin, but photoreceptor apoptosis was noted where expression of alphaA-crystallin was relatively low. The present study demonstrated that alphaA-crystallin was up-regulated in the cytoplasm of photoreceptors in the SO retina. This may play a protective role in the suppression of photoreceptor apoptosis associated with intraocular inflammation. PMID- 22052022 TI - Synthesis and biological properties of conjugates between fluoroquinolones and a N3''-functionalized pyochelin. AB - Pyochelin is a siderophore common to Pseudomonas aeruginosa and several other pathogenic bacteria. A pyochelin functionalized at the N3'' position with a propyl-amine extension was previously synthesized. In the present work we proved that this analog binds FptA, the pyochelin outer membrane receptor, and transports iron(III) efficiently into bacteria. This functionalized pyochelin seemed to be a good candidate for antibiotic vectorization in the framework of a Trojan horse prodrug strategy. In this context, conjugates between pyochelin and three fluoroquinolones (norfloxacin, ciprofloxacin and N-desmethyl-ofloxacin) were synthesized with a spacer arm that was either stable or hydrolyzable in vivo. Some pyochelin-fluoroquinolone conjugates had antibacterial activities in growth inhibition experiments on several P. aeruginosa strains. However, these activities were weaker than those of the antibiotic alone. These properties appeared to be related to both the solubility and bioavailability of conjugates and to the stability of the spacer arm used. PMID- 22052023 TI - Time-of-day effect on hip flexibility associated with the modified sit-and- reach test in males. AB - Flexibility is a key component of physical fitness. It has been suggested that measures of physical fitness components may vary throughout the day. The aim of this study was to analyse the effects of the time of day on flexibility performance. 26 men (mean age=25.4 years, SD=2.5) were evaluated by hip flexion on kinematic analysis and also by an absolute score in the modified Sit-and-Reach test during a repeated measure design. This was done during 3 experimental sessions, which took place at 8:00 a.m., 1:00 p.m. and 6:00 p.m., in random order. All subjects were previously familiarized with the test parameters. There was a diurnal variation only in the modified Sit-and-Reach test score between 8:00 a.m and 6:00 p.m. (P=0.01). There was no significant difference in the hip kinematic analysis between hours. These findings suggest that flexibility performance in the modified Sit-and-Reach test, in absolute scores, is affected by the time of day, with higher performance in the evening. PMID- 22052024 TI - AVPR2 gene and weight changes during triathlons. AB - The arginine vasopressin receptor 2 (AVPR2) plays an important antidiuretic role in regulating water balance to maintain osmotic equilibrium. The aim of this study was to determine if there were any associations between single nucleotide polymorphisms (SNPs), within the AVPR2 gene, and changes in serum sodium concentrations and/or body weight (BW) in Ironman triathletes. Caucasian male triathletes who completed either the 2000, 2001 or 2006 South African Ironman Triathlons were genotyped (n=570) for at least one SNP. Pre- and post-race serum [Na+] (pre n=514; post n=423) and BWs (pre n=556; post n=552) were measured. Triathletes were divided into 3 groups according to their relative BW loss during the triathlon (BW loss of 0-3, 3-5 and >5%). There was a significant linear trend (p=0.010, x2=6.7) for the distribution of minor haplotypes GCT, GTC and GCC across the 3 BW loss groups. The >5% group had the highest percentage (4.7%) of triathletes with minor haplotypes followed by the 3-5% (3.6%) and 3-0% (0%) groups. In conclusion, the minor haplotype constructs of AVPR2 SNPs were associated with larger BW losses during the Ironman Triathlons. This finding supports a possible genetic contribution to BW loss during endurance exercise events acting through the argine vasopression system. PMID- 22052025 TI - Step length and individual anaerobic threshold assessment in swimming. AB - Anaerobic threshold is widely used for diagnosis of swimming aerobic endurance but the precise incremental protocols step duration for its assessment is controversial. A physiological and biomechanical comparison between intermittent incremental protocols with different step lengths and a maximal lactate steady state (MLSS) test was conducted. 17 swimmers performed 7*200, 300 and 400 m (30 s and 24 h rest between steps and protocols) in front crawl until exhaustion and an MLSS test. The blood lactate concentration values ([La-]) at individual anaerobic threshold were 2.1+/-0.1, 2.2+/-0.2 and 1.8+/-0.1 mmol.l - 1 in the 200, 300 and 400 m protocols (with significant differences between 300 and 400 m tests), and 2.9+/-1.2 mmol.l - 1 at MLSS (higher than the incremental protocols); all these values are much lower than the traditional 4 mmol.l - 1 value. The velocities at individual anaerobic threshold obtained in incremental protocols were similar (and highly related) to the MLSS, being considerably lower than the velocity at 4 mmol.l - 1. Stroke rate increased and stroke length decreased throughout the different incremental protocols. It was concluded that it is valid to use intermittent incremental protocols of 200 and 300 m lengths to assess the swimming velocity corresponding to individual anaerobic threshold, the progressive protocols tend to underestimate the [La-] at anaerobic threshold assessed by the MLSS test, and swimmers increase velocity through stroke rate increases. PMID- 22052026 TI - Cardiorespiratory and neuromuscular responses during water aerobics exercise performed with and without equipment. AB - The aim of the study was to compare the cardiorespiratory and neuromuscular responses to water aerobics exercise performed with and without equipment. 15 women performed stationary jogging combined with elbow flexion/extension without equipment, with water-drag forces equipment and with water-floating equipment, at 2 submaximal cadences and at maximal cadence. Heart rate, oxygen uptake and electromyographic signal from biceps brachii, triceps brachii, biceps femoris and rectus femoris were collected during the exercise. The heart rate and oxygen uptake showed significantly higher values during the execution of the water aerobics exercise with either equipment compared to the execution without equipment. In addition, significant difference was found between submaximal cadences. For neuromuscular responses, no significant differences were found between the submaximal cadences for all muscles analyzed; however, significant differences were found between these submaximal cadences and the maximal cadence. Similarly, the results showed no significant differences between the execution of the exercise with or without equipment, except in the muscle activation of triceps brachii and biceps femoris, which was higher when using water-floating and water-drag forces equipment, respectively. In conclusion, the water aerobics exercise presented higher cardiorespiratory responses with equipment and also increased the cadence of execution. Nevertheless, neuromuscular responses were higher only at maximal cadence. PMID- 22052027 TI - Compression sleeves increase tissue oxygen saturation but not running performance. AB - The purpose of this study was to determine the effects of calf compression sleeves on running performance and on calf tissue oxygen saturation (StO2) at rest before exercise and during recovery period. 14 moderately trained athletes completed 2 identical sessions of treadmill running with and without calf compression sleeves in randomized order. Each session comprised: 15 min at rest, 30 min at 60% maximal aerobic velocity determined beforehand, 15 min of passive recovery, a running time to exhaustion at 100% maximal aerobic velocity, and 30 min of passive recovery. Calf StO2 was determined by near infra-red spectroscopy and running performance by the time to exhaustion. Compression sleeves increased significantly StO2 at rest before exercise (+ 6.4+/-1.9%) and during recovery from exercise (+ 7.4+/-1.7% and + 10.7+/-1.8% at 20th and 30th min of the last recovery period, respectively). No difference was observed between the times to exhaustion performed with and without compression sleeves (269.4+/-18.4 s and 263.3+/-19.8 s, respectively). Within the framework of this study, the compression sleeves do not improve running performance in tlim. However the StO2 results argue for further interest of this garment during effort recovery. PMID- 22052028 TI - Physiological responses to treadmill and cycle exercise. AB - This study aimed to identify differences in the acute cardio-respiratory, metabolic and perceptual responses between exercise performed on the treadmill and on the cycle ergometer at several intensities. The sample comprised of 20 voluntary male participants (age=22.5 +/- 1.8 years; height=177.7 +/- 7.0 cm; body mass=72.6 +/- 7.9 kg; fat mass=7.87 +/- 1.3%) that performed 5 submaximal 8 min exercise bouts, interspersed with a 10 min period of passive recovery. Exercise intensity used on the treadmill was 10, 12, 14, 15 and 16 km/h (0% gradient), and 80, 120, 160, 180 and 200 W on the cycle ergometer (65-70 rpm). There was a significant mode effect and also mode*intensity interaction in oxygen uptake and heart rate with higher values in the treadmill protocol (F=32.0 p=0.000, eta2=0.65 and F=132.0 p=0.000, eta2=0.88, respectively). The respiratory exchange ratio and blood lactate concentrations were not different across modes (F1, 18=1.9 p=0.183 and F1, 17=0.1 p=0.964, respectively) and rate of perceived exertion values were higher in the cycle ergometer (F1, 12=1.2 p=0.288). Generally, results showed a larger exercise mode effect on the cardio-respiratory variables with higher response patterns on the treadmill, differing according to exercise intensity. PMID- 22052029 TI - Incidence of injuries in French professional soccer players. AB - In this prevalence cohort study, injuries sustained during 15 seasons in a professional soccer team were investigated according to the different soccer seasons, number of matches per season, month the injury occurred, location, severity, playing position and the team's rank at the end of the French professional championship. Altogether, 903 injuries in 173 professional soccer players were reported. Injury incidence per 1 000 h of exposure during matches and training was 4.7+/-5. This incidence did not vary significantly between seasons. However, injury incidence increased after the year 2003 and constantly exceeded 4.2. In the same way, after 2002 muscle injury incidence always exceeded 2 per 1 000 h of exposure. Injury incidence peaked during the month of January. Hamstring muscle injury represented the most frequent injury. No difference in injury incidence was found according to the playing position or to the season whether the team participated or not in the European cup. No correlation was found with the team's rank at the end of the French championship. This study highlighted no significant variation on injury incidence over a 15-season period except for the muscle injury rate in high level soccer players. PMID- 22052030 TI - Effects of sprint interval training on elite Judoists. AB - The purpose of this study was to investigate the effect of sprint interval training (SIT) compared to control group (CG). 29 Judoists were assigned to SIT group (n=11, age 20.00+/-1.10 years) and CG (n=18, age 19.94+/-1.16 years). There were no significant changes in body fat and aerobic performance (VO2max, HRmax, and HR after Judo match) after 4 and 8 weeks. However, anaerobic peak power and mean power in SIT group was significantly increased by 16% and 17% at 4 weeks and by 17% and 22% at 8 weeks compared to baseline values (p<0.05). At 8 weeks, blood lactate concentration after graded exercise was significantly decreased in SIT group compared to CG after 10 and 15 min of recovery (p< 0.05). After Judo match, triglyceride and epinephrine were significantly increased in CG compared to SIT group (p<0.05) at 4 and 8 weeks. Otherwise, there were no significant changes of total cholesterol, albumin, FFA, and norepinephrine in both groups. We suggested that SIT program for elite Judoists would be effective to increase anaerobic power in a short period during off-season training. PMID- 22052031 TI - The antinociceptive efficacy of HWTX-I epidurally administered in rheumatoid arthritis rats. AB - Rheumatoid arthritis (RA) is one of the inflammatory kinds of arthritis in the clinical situation, and cytosolic Ca2+ overload has been proposed as one of the primary factors for many inflammatory cells activation, which lead to relative enzymes and inflammatory factors release. It is therefore accepted that Ca2+ channel blockers can protect joint injury from inflammation. In the present study we investigated the possible molecular mechanism of the antinociceptive efficacy of HWTX-I, a spider peptide toxin blocking Ca2+ channels, on the rat rheumatoid arthritis model. Our study demonstrates that HWTX-I can relieve pain in the inflammatory joints and eliminate arthrocele to some degree. Moreover, HWTX-I can also decrease the concentration of tumour necrosis factor alpha (TNF-alpha) and increase the concentration of interleukin 4(IL-4) and interleukin 10(IL-10) in rat's serum. HWTX-I can also decrease the mRNA expression level of related factors of TNF-alpha, interleukin 1beta (IL-1beta) and interleukin 6(IL-6) in inflammatory pathways in rheumatoid arthritis. Therefore, the present results show that the epidural administration of HWTX-I is effective in antinociception in the rat model of rheumatoid arthritis, which may act through its inhibition on certain inflammatory pathways. PMID- 22052032 TI - The record power profile to assess performance in elite cyclists. AB - The purpose of this study was to assess the Record Power Profile (RPP) of cyclists, i. e., the relationship between different record Power Output (PO) and the corresponding durations through a whole race season. We hypothesized that PO of different effort durations could differ according to the cyclist's category and race performance profile. 17 cyclists (9 professionals and 8 elites) performed all trainings and competitions during 10 months with a mobile power meter device (SRM) mounted on their bike. The results show that the cyclists' RPP is a hyperbolic relationship between the different record PO and time durations. It significantly reflects the characteristics of different skills: (1) sprinters have the highest record PO within zone 5, (2) climbers present the highest record PO within zones 2-3 and, (3) climbers and flat specialists have higher zone 1 record PO than sprinters. These results suggest that the RPP represents "a signature" of the cyclists' physical capacity and that it allows the determination of different training intensities. The RPP appears as a new concept that is interesting for coaches and scientists in order to evaluate performance in cycling. PMID- 22052033 TI - Time motion and video analysis of classical ballet and contemporary dance performance. AB - Video analysis has become a useful tool in the preparation for sport performance and its use has highlighted the different physiological demands of seemingly similar sports and playing positions. The aim of the current study was to examine the performance differences between classical ballet and contemporary dance. In total 93 dance performances (48 ballet and 45 contemporary) were analysed for exercise intensity, changes in direction and specific discrete skills (e. g., jumps, lifts). Results revealed significant differences between the 2 dance forms for exercise intensity (p<0.001), changes in direction (p<0.001) and discrete skills (p<0.05) with gender differences noted in the latter (p<0.05). Ballet was characterised by longer periods at rest (38 s x min(-1)) and high to very high exercise intensities (9 s x min(-1)), whilst contemporary dance featured more continuous moderate exercise intensities (27 s x min(-1)). These differences have implications on the energy systems utilised during performance with ballet potentially stressing the anaerobic system more than contemporary dance. The observed high rates in the discrete skills in ballet (5 jumps x min(-1); 2 lifts x min(-1)) can cause local muscular damage, particularly in relatively weaker individuals. In conclusion, classical ballet and contemporary dance performances are as significantly different in the underlying physical demands placed on their performers as the artistic aspects of the choreography. PMID- 22052034 TI - Optimising the acquisition and retention of heat acclimation. AB - Heat acclimation (HA) often starts in a moderately hot environment to prevent thermal overload and stops immediately prior to athletic activities. The aims of this study were (1) to establish whether acclimation to a moderately hot climate is sufficient to provide full acclimation for extreme heat and (2) to investigate the physiological responses to heat stress during the HA decay period. 15 male subjects exercised for 9 consecutive days at 26 degrees C Wet Bulb Globe Temperature (WBGT) and 3 days at 32 degrees C WBGT on a cycle ergometer for up to 2 h per day and repeated the exercise 3, 7 and 18 days later in 26 degrees C WBGT. Rectal temperature (T (re)) and heart rate (HR) were measured during 60 min of steady state exercise (~45% of maximum oxygen uptake). During days 1-9, end exercise T (re) was reduced from 38.7+/-0.1 to a plateau of 38.2+/-0.1 degrees C (p<0.05), HR was reduced from 156+/-10 to 131+/-11 bpm (p<0.05). No changes in HR and T (re) occurred during the 3 days in the very hot environment. However, T (re) during rest and exercise were significantly lower by 0.4-0.5 degrees C after HA compared with day 9, suggesting that heat acclimation did not decay but resulted in further favourable adaptations. PMID- 22052035 TI - High and rising health care costs. AB - The U.S. is spending a growing share of the GDP on health care, outpacing other industrialized countries. This synthesis examines why costs are higher in the U.S. and what is driving their growth. Key findings include: health care inefficiency, medical technology and health status (particularly obesity) are the primary drivers of rising U.S. health care costs. Health payer systems that reward inefficiencies and preempt competition have impeded productivity gains in the health care sector. The best evidence indicates medical technology accounts for one-half to two-thirds of spending growth. While medical malpractice insurance and defensive medicine contribute to health costs, they are not large enough factors to significantly contribute to a rise in spending. Research is consistent that demographics will not be a significant factor in driving spending despite the aging baby boomers. PMID- 22052036 TI - Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1-eNOS axis. AB - Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD(+)-dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion. PMID- 22052037 TI - Intramuscular Transplantation of Muscle Precursor Cells over-expressing MMP-9 improves Transplantation Success. AB - Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin in muscles. A therapeutic approach to restore dystrophin expression in DMD patient's muscles is the transplantation of muscle precursor cells (MPCs). However, this transplantation is limited by the low MPC capacity to migrate beyond the injection trajectory. Matrix metalloproteases (MMPs) are key regulatory molecules in the remodeling of extracellular matrix (ECM) components. MPCs over-expressing MMP-9 were tested by zymography, migration and invasion assays in vitro and by transplantation in mouse muscle. In vitro, MPCs over expressing MMP-9 have a better invasion capacity than control MPCs. When these cells are transplanted in mouse muscles, the transplantation success is increased by more than 50% and their dispersion is higher than normal cells. MMP-9 over expression could thus be an approach to improve cell transplantation in DMD patients by increasing the dispersion capacity of transplanted cells. PMID- 22052039 TI - The outcome of initial percutaneous drainage versus surgical drainage for intra abdominal abscesses in Crohn's disease. AB - PURPOSE: Percutaneous drainage (PD) of Crohn's related abscesses is becoming popular with the development of techniques. We retrospectively analyzed the outcome of initial PD versus initial surgical drainage for intra-abdominal abscesses in Crohn's disease. METHODS: Twenty-three patients of Crohn's disease complicated with intra-abdominal or pelvic abscesses treated in our institution between July 2001 and April 2010 were retrospectively identified from 188 patients with proven Crohn's disease. Outcome measures included abscess recurrence after different treatments, post-drainage complications, ultimate stoma creation, and subsequent surgery for Crohn's disease. RESULTS: Patients were divided into initial PD group (n = 10) and initial surgery group (n = 13): post-drainage complications were more common in initial surgery group (2/10 vs 9/13, P = 0.036), abscess recurred in three patients (2/10 vs 1/13, NS), and subsequent surgery was needed in 10 patients (6/10 vs 4/13, NS). Ultimate stoma creation were significantly more in initial surgery group (1/10 vs 9/13, P = 0.01). CONCLUSIONS: Initial PD group had lower rate of post-drainage complications and ultimate stoma creation compared to the initial surgery group. Although subsequent surgery may not be avoided after PD, it can provide safe anastomosis for resections. Long-term follow-up should be done to assess the outcome of PD. PMID- 22052040 TI - Stapled and conventional Milligan-Morgan haemorrhoidectomy: different solutions for different targets. AB - PURPOSE: Haemorrhoidal disease is one of the most common anorectal disorders. The aim of this study is to compare the results, over the last 10 years, of stapled haemorrhoidopexy (SH) with those of standard Milligan-Morgan haemorrhoidectomy (M&M). Furthermore, we discuss the proper indications for each technique in terms of the lowest rate of complications and long-term results. METHODS: Three hundred forty-three patients with different degrees of symptomatic haemorrhoids underwent SH or M&M from January 2005 to December 2007. Patients were divided into two groups, age and sex matched. The administration of painkillers drugs, antibiotics and laxatives, complication symptoms and hospital stay in all the patients were recorded after surgical treatment. RESULTS: The mean operative time was shorter in the stapled group compared to that in the open group (31 min versus 40 min). Postoperative pain, hospital stay and return to full activity were shorter in the stapled group. There was a significant difference in the wound healing time between the two groups. We noticed a higher rate of recurrence in patients treated with stapled haemorrhoidectomy for fourth-degree haemorrhoids. CONCLUSIONS: According to our experience, the Longo technique is indicated for the treatment of haemorrhoids of second- and third degree. In the latter grades of prolapse, the Milligan-Morgan haemorrhoidectomy can also be applied with good outcomes. We believe that, in case of irreducible prolapse, the M&M is to be preferred. However, operative management varies according to surgeon's interest and is tailored to meet the individual patient's need. PMID- 22052041 TI - Tumor location is a prognostic factor in poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet-ring cell carcinoma of the colon. AB - PURPOSE: Cancers which arise in the proximal and distal colon are suggested to be different clinically, pathologically, and genetically. The aim of this study is to clarify whether clinical behavior of colonic poorly differentiated adenocarcinoma, mucinous adenocarcinoma, and signet-cell carcinoma (Por/Muc/Sig cancers), minor and aggressive subpopulation in colonic cancers, differs in accordance with the tumor location. METHODS: A total of 3,175 patients with curatively resected colonic cancers were studied. Clinical and pathological features were compared between Por/Muc/Sig cancers and well or moderately differentiated adenocarcinomas (Wel/Mod cancers) and between proximal and distal cancers in each histologic type. RESULTS: Por/Muc/Sig cancers (n = 213) were more advanced in the TNM stage and showed worse disease-specific survival than Wel/Mod cancers (n = 2,692). In Por/Muc/Sig cancers, but not in Wel/Mod cancers, proximal cancers showed significantly better disease-specific survival than distal cancers (88.9% vs. 76.5%, p = 0.0234), and a multivariate analysis showed that proximal tumor location was an independent predictor of fair prognosis (hazard ratio (HR), 0.458; 95% confidence interval (CI), 0.218-0.961; p = 0.0390). In addition, female gender also was an independent predictor of fair prognosis in Por/Muc/Sig cancers (HR, 0.373; 95% CI, 0.151-0.922) and not in Wel/Mod cancers. CONCLUSIONS: Proximal Por/Muc/Sig cancers were suggested to be a distinct subpopulation with a favorable oncologic outcome. Tumor location and gender might be helpful in the risk stratification after curative surgery for Por/Muc/Sig cancers. PMID- 22052042 TI - Compendium of animal rabies prevention and control, 2011. AB - Rabies has one of the highest case-fatality ratios of any infectious disease. This report provides recommendations for public health officials, veterinarians, animal control officials, and other parties engaged in rabies prevention and control activities and should serve as the basis for standardizing procedures among jurisdictions. The recommendations regarding domestic animal vaccination, management of animals exposed to rabies, and management of animals that bite humans are the core elements of animal rabies control and human rabies prevention. These updated 2011 guidelines include the national case definition for animal rabies and clarify the role of the CDC rabies laboratory in providing confirmatory testing of suspect animals. The table of rabies vaccines licensed and marketed in the United States has been updated, and additional references have been included to provide scientific support for information in this report. PMID- 22052043 TI - Delivering a pharmacogenetic service: is there a role for genetic counselors? AB - Pharmacogenetics, the use of genetic information to direct safer and or more effective prescription of medication, is a relatively new clinical concept. Currently, there is no consensus regarding which healthcare professionals should deliver pharmacogenetic services. This study explored the opinions of genetic counselors about their potential role in delivering pharmacogenetic services. Semi-structured face-to-face interviews were conducted with 14 genetic counselors. Four vignettes describing pharmacogenetic testing scenarios were used to elicit views on specific clinical applications. Data were analysed using the constant comparative method. Opinions varied, but the majority of interviewees suggested that genetic counselors could have a role. However, participants suggested that additional training would be needed due to counselors' limited knowledge of pharmacogenetics. Employing genetic counselors in a specialist role within a multidisciplinary clinic was suggested as a model of service delivery. Service models developed for pharmacogenetic testing may need to be adapted according to the issues presented by each type of test. PMID- 22052044 TI - Challenging endeavour for preservation of freeze-dried mammalian spermatozoa. AB - Freeze-drying (lyophilization) has been proposed as an alternative method for sperm preservation to overcome the disadvantages of the current cryopreservation method such as the high maintenance cost of frozen stocks, the problems associated with transportation of frozen materials and the potential risk of total loss of the frozen stock. Since freeze-dried spermatozoa after rehydration lose their motility, which is an essential requirement to complete physiological fertilization, a relatively difficult microinsemination technique must be applied to rehydrated spermatozoa. Theoretically, it has been supposed that freeze-dried spermatozoa could maintain their functions and abilities to interact with the oocyte cytoplasm after prolonged storage at refrigerator temperature. However, sufficient yield of transferable blastocysts and production of live offspring derived from freeze-dried sperm samples are still subjects to be challenged and overcome in large domestic species. PMID- 22052045 TI - Environmental lead after Hurricane Katrina: implications for future populations. AB - BACKGROUND: As a result of Hurricane Katrina, > 100,000 homes were destroyed or damaged and a significant amount of sediment was deposited throughout the city of New Orleans, Louisiana. Researchers have identified the potential for increased lead hazards from environmental lead contamination of soils. OBJECTIVES: We assessed the distribution of residential soil and dust lead 2 years poststorm and compared soil lead before and after the storm. METHODS: We conducted a cross sectional study in New Orleans in which households were selected by stratified random sampling. A standard residential questionnaire was administered, and lead testing was performed for both the interior and exterior of homes. Logistic regression was used to identify significant predictors of interior and exterior lead levels in excess of allowable levels. RESULTS: One hundred nine households were enrolled; 61% had at least one lead measurement above federal standards. Of homes with bare soil, 47% had elevated lead and 27% had levels exceeding 1,200 ppm. Housing age was associated with soil lead, and housing age and soil lead were associated with interior lead. Race, income, and ownership status were not significantly associated with either interior or exterior lead levels. The median soil lead level of 560 ppm was significantly higher than the median level of samples collected before Hurricane Katrina. CONCLUSIONS: The high prevalence (61%) of lead above recommended levels in soil and dust samples in and around residences raises concern about potential health risks to the New Orleans population, most notably children. Steps should be taken to mitigate the risk of exposure to lead-contaminated soil and dust. Further research is needed to quantify the possible contribution of reconstruction activities to environmental lead levels. PMID- 22052046 TI - The renal papilla: an enigma in damage and repair. PMID- 22052047 TI - Development of the renal arterioles. AB - The kidney is a highly vascularized organ that normally receives a fifth of the cardiac output. The unique spatial arrangement of the kidney vasculature with each nephron is crucial for the regulation of renal blood flow, GFR, urine concentration, and other specialized kidney functions. Thus, the proper and timely assembly of kidney vessels with their respective nephrons is a crucial morphogenetic event leading to the formation of a functioning kidney necessary for independent extrauterine life. Mechanisms that govern the development of the kidney vasculature are poorly understood. In this review, we discuss the anatomical development, embryological origin, lineage relationships, and key regulators of the kidney arterioles and postglomerular circulation. Because renal disease is associated with deterioration of the kidney microvasculature and/or the reenactment of embryonic pathways, understanding the morphogenetic events and processes that maintain the renal vasculature may open new avenues for the preservation of renal structure and function and prevent the progression of renal disease. PMID- 22052048 TI - Prorenin receptor is essential for normal podocyte structure and function. AB - The prorenin receptor is an accessory subunit of the vacuolar H(+)-ATPase, suggesting that it has fundamental functions beyond activation of the local renin angiotensin system. Podocytes express the prorenin receptor, but its function in these cells is unknown. Here, podocyte-specific, conditional, prorenin receptor knockout mice died of kidney failure and severe proteinuria within 4 weeks of birth. The podocytes of these mice exhibited foot process effacement with reduced and altered localization of the slit-diaphragm proteins nephrin and podocin. Furthermore, the podocytes contained numerous autophagic vacuoles, confirmed by enhanced accumulation of microtubule-associated protein 1 light chain 3-positive intracellular vesicles. Ablation of the prorenin receptor selectively suppressed expression of the V(0) c-subunit of the vacuolar H(+)-ATPase in podocytes, resulting in deacidification of intracellular vesicles. In conclusion, the prorenin receptor is important for the maintenance of normal podocyte structure and function. PMID- 22052049 TI - Innate immunity and dendritic cells in kidney disease and the nobel prize. PMID- 22052050 TI - The prorenin receptor: what's in a name. PMID- 22052051 TI - Is the malnutrition-inflammation complex the secret behind greater survival of African-American dialysis patients? PMID- 22052052 TI - AT1 receptors in the collecting duct directly modulate the concentration of urine. AB - Mice lacking AT(1) angiotensin receptors have an impaired capacity to concentrate the urine, but the underlying mechanism is unknown. To determine whether direct actions of AT(1) receptors in epithelial cells of the collecting duct regulate water reabsorption, we used Cre-Loxp technology to specifically eliminate AT(1A) receptors from the collecting duct in mice (CD-KOs). Although levels of AT(1A) receptor mRNA in the inner medulla of CD-KO mice were significantly reduced, their kidneys appeared structurally normal. Under basal conditions, plasma and urine osmolalities and urine volumes were similar between CD-KO mice and controls. The increase in urine osmolality in response to water deprivation or vasopressin administration, however, was consistently attenuated in CD-KO mice. Similarly, levels of aquaporin-2 protein in inner and outer medulla after water deprivation were significantly lower in CD-KO mice compared with controls, despite its normal localization to the apical membrane. In summary, these results demonstrate that AT(1A) receptors in epithelial cells of the collecting duct directly modulate aquaporin-2 levels and contribute to the concentration of urine. PMID- 22052053 TI - Antifibrotic effect of tamoxifen in a model of progressive renal disease. AB - Tamoxifen, a selective estrogen receptor modulator, has antifibrotic properties; however, whether it can attenuate renal fibrosis is unknown. In this study, we tested the effects of tamoxifen in a model of hypertensive nephrosclerosis (chronic inhibition of nitric oxide synthesis with L-NAME). After 30 days, treated rats had significantly lower levels of albuminuria as well as lower histologic scores for glomerulosclerosis and interstitial fibrosis than untreated controls. Tamoxifen was renoprotective despite having no effect on the sustained, severe hypertension induced by L-NAME. Tamoxifen prevented the accumulation of extracellular matrix by decreasing the expression of collagen I, collagen III, and fibronectin mRNA and protein. These renoprotective effects associated with inhibition of TGF-beta1 and plasminogen activator inhibitor-1, and with a significant reduction in alpha-smooth muscle actin-positive cells in the renal interstitium. Furthermore, tamoxifen abrogated IL-1beta- and angiotensin-II induced proliferation of fibroblasts from both kidney explants and from the NRK 49F cell line. Tamoxifen also inhibited the expression of extracellular matrix components and the production and release of TGF-beta1 into the supernatant of these cells. In summary, tamoxifen exhibits antifibrotic effects in the L-NAME model of hypertensive nephrosclerosis, likely through the inhibition of TGF beta1, suggesting that it may have therapeutic use in CKD treatment. PMID- 22052054 TI - Notch promotes dynamin-dependent endocytosis of nephrin. AB - Notch signaling in podocytes causes proteinuria and glomerulosclerosis in humans and rodents, but the underlying mechanism remains unknown. Here, we analyzed morphologic, molecular, and cellular events before the onset of proteinuria in newborn transgenic mice that express activated Notch in podocytes. Immunohistochemistry revealed a loss of the slit diaphragm protein nephrin exclusively in podocytes expressing activated Notch. Podocyte-specific deletion of Rbpj, which is essential for canonical Notch signaling, prevented this loss of nephrin. Overexpression of activated Notch decreased cell surface nephrin and increased cytoplasmic nephrin in transfected HEK293T cells; pharmacologic inhibition of dynamin, but not depletion of cholesterol, blocked these effects on nephrin, suggesting that Notch promotes dynamin-dependent, raft-independent endocytosis of nephrin. Supporting an association between Notch signaling and nephrin trafficking, electron microscopy revealed shortened podocyte foot processes and fewer slit diaphragms among the transgenic mice compared with controls. These data suggest that Notch signaling induces endocytosis of nephrin, thereby triggering the onset of proteinuria. PMID- 22052055 TI - A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy. AB - Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44+/-27 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or <20% interstitial fibrosis (24%). TMA rarely occurred in the absence of significant proteinuria. During follow-up, a doubling of serum creatinine or ESRD occurred in all patients with laboratory evidence of TMA, in 42% of those with morphologic evidence but no laboratory evidence of TMA, and in 11% of those without TMA. In summary, lesions of TMA are frequent in IgA nephropathy and may occur in normotensive patients with near-normal renal histology. Although the pathophysiologic mechanisms involved remain undetermined, the current study rules out severe hypertension or advanced renal disease as sole causes. PMID- 22052056 TI - Immune profile of pediatric renal transplant recipients following alemtuzumab induction. AB - The incidence of developing circulating anti-human leukocyte antigen antibodies and the kinetics of T cell depletion and recovery among pediatric renal transplant recipients who receive alemtuzumab induction therapy are unknown. In a collaborative endeavor to minimize maintenance immunosuppression in pediatric renal transplant recipients, we enrolled 35 participants from four centers and treated them with alemtuzumab induction therapy and a steroid-free, calcineurin inhibitor-withdrawal maintenance regimen. At 3 months after transplant, there was greater depletion of CD4(+) than CD8(+) T cells within the total, naive, memory, and effector memory subsets, although depletion of the central memory subset was similar for CD4(+) and CD8(+) cells. Although CD8(+) T cells recovered faster than CD4(+) subsets overall, they failed to return to pretransplant levels by 24 months after transplant. There was no evidence for greater recovery of either CD4(+) or CD8(+) memory cells than naive cells. Alemtuzumab relatively spared CD4(+)CD25(+)FoxP3(+) regulatory T cells, resulting in a rise in their numbers relative to total CD4(+) cells and a ratio that remained at least at pretransplant levels throughout the study period. Seven participants (20%) developed anti-human leukocyte antigen antibodies without adversely affecting allograft function or histology on 2-year biopsies. Long-term follow-up is underway to assess the potential benefits of this regimen in children. PMID- 22052057 TI - Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. AB - The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics. PMID- 22052058 TI - Clusterin attenuates the development of renal fibrosis. AB - Upregulation of clusterin occurs in several renal diseases and models of nephrotoxicity, but whether this promotes injury or is a protective reaction to injury is unknown. Here, in the mouse unilateral ureteral obstruction model, obstruction markedly increased the expression of clusterin, plasminogen activator inhibitor-1 (PAI-1), type I collagen, and fibronectin. Compared with wild-type mice, clusterin-deficient mice exhibited higher levels of PAI-1, type I collagen, and fibronectin and accelerated renal fibrosis in response to obstruction. In cultured rat tubular epithelium-like cells, adenovirus-mediated overexpression of clusterin inhibited the expression of TGF-beta-stimulated PAI-1, type I collagen, and fibronectin. Clusterin inhibited TGF-beta-stimulated Smad3 activity via inhibition of Smad3 phosphorylation and its nuclear translocation. Moreover, intrarenal delivery of adenovirus-expressing clusterin upregulated expression of clusterin in tubular epithelium-like cells and attenuated obstruction-induced renal fibrosis. In conclusion, clusterin attenuates renal fibrosis in obstructive nephropathy. These results suggest that upregulation of clusterin during renal injury is a protective response against the development of renal fibrosis. PMID- 22052059 TI - Comments on sudden death due to polyarteritis nodosa. PMID- 22052060 TI - miR-150 as a potential biomarker associated with prognosis and therapeutic outcome in colorectal cancer. AB - BACKGROUND: MicroRNAs (miRNA) have potential as prognostic biomarkers and therapeutic targets in cancer. A study was undertaken to investigate the association between miRNA expression patterns and the prognosis and therapeutic outcome of colorectal cancer (CRC). METHODS: miRNA expression profiling in tumour, adenoma and normal colorectal tissues was performed to identify tumour related miRNAs in the course of colorectal malignant changes. Quantitative reverse transcription PCR (qRT-PCR) assays were used to measure tumour-related miRNA and to assess its association with survival and response to adjuvant chemotherapy in 239 patients. In addition, to validate the findings, associations of the tumour-related miRNA with clinical characteristics of CRC were analysed in 185 patients by in situ hybridisation (ISH) analysis. RESULTS: Only one miR-150 was found to show a decrease in expression levels in the three tissue groups (normal, adenoma and cancer tissue) in parallel with increasing carcinogenesis of the colorectal tissue. In both ISH and qRT-PCR analysis, tumour tissue had reduced levels of miR-150 expression compared with paired non-cancerous tissue, which indicated that the levels of miR-150 expression were associated with CRC. Moreover, patients whose tumours had low miR-150 expression had shorter survival and a worse response to adjuvant chemotherapy than patients whose tumours had high miRNA expression. CONCLUSIONS: The miR-150 expression status of patients with CRC is associated with survival and response to adjuvant chemotherapy. It is suggested that miR-150 should be considered as a potential biomarker associated with the prognosis and therapeutic outcome in CRC. PMID- 22052061 TI - Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells. AB - BACKGROUND: Intestinal homoeostasis is dependent on immunological tolerance to the microbiota. OBJECTIVE: To (1) determine if a probiotic could induce Foxp3 T cells in humans; (2) to elucidate the molecular mechanisms, which are involved in the induction of Foxp3 T cells by human dendritic cells. DESIGN: Cytokine secretion and Foxp3 expression were assessed in human volunteers following Bifidobacterium infantis feeding. Monocyte-derived dendritic cells (MDDCs), myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) were incubated in vitro with B. infantis and autologous lymphocytes. Transcription factor expression, costimulatory molecule expression, cytokine secretion, retinoic acid and tryptophan metabolism were analysed. RESULTS: Volunteers fed B. infantis displayed a selective increase in secretion of interleukin (IL)-10 and enhanced Foxp3 expression in peripheral blood. In vitro, MDDCs, mDCs and pDCs expressed indoleamine 2,3-dioxygenase and secreted IL-10, but not IL-12p70, in response to B. infantis. MDDC and mDC IL-10 secretion was Toll-like receptor (TLR)-2/6 dependent, while pDC IL-10 secretion was TLR-9 dependent. In addition, MDDCs and mDCs expressed RALDH2, which was TLR-2 and DC-SIGN dependent. B. infantis-stimulated MDDCs, mDCs and pDCs induced T cell Foxp3 expression. TLR-2, DC-SIGN and retinoic acid were required for MDDC and mDC induction of Foxp3 T cells, while pDCs required indoleamine 2,3-dioxygenase. CONCLUSIONS: B. infantis administration to humans selectively promotes immunoregulatory responses, suggesting that this microbe may have therapeutic utility in patients with inflammatory disease. Cross-talk between multiple pattern-recognition receptors and metabolic pathways determines the innate and subsequent T regulatory cell response to B. infantis. These findings link nutrition, microbiota and the induction of tolerance within the gastrointestinal mucosa. PMID- 22052062 TI - Nottingham trial of faecal occult blood testing for colorectal cancer: a 20-year follow-up. AB - BACKGROUND: Three large randomised trials have shown that screening for colorectal cancer (CRC) using the faecal occult blood test (FOBt) can reduce the mortality from this disease. The largest of these trials, conducted in Nottingham since 1981, randomised 152,850 individuals between the ages of 45 and 74 years to an intervention arm receiving biennial Haemoccult (FOB) test kit or to a control arm. In 2006, the National Bowel Cancer Screening Programme was launched in England using the FOBt, with the expectation that it will reduce CRC mortality. AIMS: To compare the CRC mortality and incidence in the intervention arm with the control arm after long-term follow-up. METHODS: The 152,850 randomised individuals were followed up through local health records and central flagging (Office for National Statistics). RESULTS: At a median follow-up of 19.5 years there was a 13% reduction in CRC mortality (95% CI 3% to 22%) in the intervention arm despite an uptake at first invitation of approximately 57%. The CRC mortality reduction in those accepting the first screening test, adjusted for the rate of non-compliers, was 18%. There was no significant difference in mortality from causes other than CRC between the intervention and control arms. Despite removing 615 adenomas >10 mm in size from the intervention arm, there was no significant difference in CRC incidence between the two arms. CONCLUSIONS: Although the reduction in CRC mortality was sustained, further follow-up of the screened population has not shown a significant reduction in the CRC incidence. Moreover, despite the removal of many large adenomas there was no reduction in the incidence of invasive cancer which was independent of sex and site of the tumour. PMID- 22052064 TI - CPEB1, a novel gene silenced in gastric cancer: a Drosophila approach. AB - BACKGROUND: Gastric cancer (GC) is a highly prevalent disease, being the fourth most common cancer and the second leading cause of cancer-associated deaths worldwide. Although many genes have been implicated in its development, many cases remain genetically unexplained. Hence, there is an urgent need to find new disease-related genes. METHODS: A transgenic Drosophila model was used to screen for novel genes putatively involved in GC. The authors evaluated the expression of the most interesting candidates in GC cell lines and primary tumours by semi quantitative reverse transcription PCR, dissected the molecular mechanisms responsible for the deregulation of the most relevant one, and analysed its functional role in vitro and in a chicken embryo model. RESULTS: Six candidate genes were identified, of which cytoplasmic polyadenylation element binding protein 1 (CPEB1) was downregulated in all GC cell lines and in 11 of 12 primary GC tumours. The pivotal CPEB1 promoter CpG site was determined, and it was found that methylation at this 79th CpG site was associated with CPEB1 silencing in GC cell lines and primary tumours. It was also discovered that methylation of this site was significantly more prevalent in diffuse type GC (p=0.007) and in cases with lymph node metastases (p=0.042). In vitro, CPEB1 impaired invasion. Its antiangiogenic role was also discovered, which was associated with downregulation of MMP14 and VEGFA. CONCLUSIONS: The first evidence of CPEB1 involvement in GC is presented, along with the molecular mechanism underlying the regulation of its expression and its potential role in invasion and angiogenesis. PMID- 22052065 TI - Intestinal expression of SHIP in inflammatory bowel diseases. PMID- 22052066 TI - Peripheral arterial tone: assessment of microcirculatory function in pregnancy. AB - OBJECTIVE: Endothelial dysfunction is known to play a key role in the pathogenesis of preeclampsia, but the majority of methods for its detection are too invasive to be used in pregnancy. In this study we report a novel method - peripheral arterial tonometry (PAT) - for examining microcirculatory function in pregnancy. METHODS: One hundred and eighty women with at least two risk factors for preeclampsia were examined at gestational weeks 16 and 28; 80 women were examined at 6-9 months postnatally. Twenty-four women developed preeclampsia or pregnancy-induced hypertension (cases), 156 remained normotensive (controls). PAT was measured using fingertip pneumatic probes; after baseline recordings the study arm was occluded with a blood pressure cuff then released after 5 min, causing reactive hyperaemia. PAT recordings pre and post occlusion were used to generate the reactive hyperaemia index (RHI). RESULTS: RHI was significantly lower at gestational week 28 compared to week 16, both in cases and controls. Baseline pulse amplitude was significantly higher at week 28 compared to week 16. There was no difference in RHI at either week 16 or 28 between cases and controls. Postnatally, there was no difference in RHI between cases and controls, but baseline pulse amplitude was lower in affected women. CONCLUSION: PAT and other methods which rely on flow-mediated dilatation for detection of endothelial dysfunction are less likely to be reliable in later pregnancy, when women are more vasodilated. PAT did not predict the development of hypertensive pregnancy complications, but demonstrated a relative peripheral vasoconstriction in affected women postnatally. PMID- 22052067 TI - Vitamin E reduces hepatic fibrosis in mice with Schistosoma japonicum infection. AB - To investigate whether vitamin E protects against hepatic fibrosis in mice with Schistosoma japonicum infection, 24 pathogen-free Kunming mice were selected and randomly divided into four groups: control (uninfected, untreated), model (infected, untreated), low-dose intervention (infected, vitamin E-treated, 30 mg/g bodyweight/day) and high-dose intervention (infected, vitamin E-treated, 60 mg/g bodyweight/day). Mice were infected with Schistosoma japonicum by inoculating abdominal skin with snail hosts. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were detected in hepatic tissue by colorimetry. The expression levels of laminin (LN), hyaluronic acid (HA), procollagen type III (PC-III) and type IV collagen (IV-C) were detected in the serum by radioimmunoassay. Finally, areas and numbers of granulomas were assessed through histopathology 42 days following treatment. The results revealed that mean areas of granulomas were smaller in the low- and high-dose intervention groups compared to those in the model group. Furthermore, the higher dose of vitamin E resulted in smaller granulomas than the low dose. The levels of LN, HA, PC-III and IV-C in the serum were lower following vitamin E treatment than in the model group. By contrast, activity of SOD, GPx and CAT in hepatic tissue was higher following vitamin E treatment compared to the model group. The activity of MDA was lower in hepatic tissue following vitamin E treatment compared to the model group, but was higher compared to controls. In general, the higher dose of vitamin E affected measurements to a greater extent than the lower dose. In conclusion, vitamin E treatment may reduce the growth of granulomas, slowing the process of hepatic fibrosis, and this effect may be the result of the altered activity of the oxidation-reduction enzyme system. PMID- 22052068 TI - Structure, stability and spectral signatures of monoprotic carborane acid-water clusters (CBW(n), where n = 1-6). AB - The gas phase structure, stability, spectra, and proton transfer properties of monoprotic carborane acid-water clusters [CB(11)F(m)H(11-m)(OH(2))(1)]-(H(2)O)(n) (where m = 0, 5, and 10; n = 1-6) have been calculated using density functional theory (DFT) with the Becke's three-parameter hybrid exchange functional and Lee Yang-Parr correlation functional (B3LYP) using 6-31+G* basis set. Results reveal that Eigen cation defects are found in CBW(n) (where n = 2-6) clusters and these clusters are significantly more stable than the non-Eigen geometry. In addition to the conventional hydrogen bond (H-bond) the role of dihydrogen bond (DHB) and halogen bond (XB) in the stabilization of these clusters can be observed from the molecular graphs derived from the atoms in molecules (AIM) analysis. Spectral information shows the features of Eigen cation and proton oscillation involved in the proton transfer process. The dissociation of proton from the perfluoro derivatives with two water molecules is more favorable when compared to the other derivatives. PMID- 22052069 TI - Abstracts of the 36th Annual IUGA (International Urogynecological Association) Meeting. Lisbon, Portugal. June 28-July 2, 2011. PMID- 22052070 TI - Contrast-enhanced ultrasonography is more sensitive than grayscale and power Doppler ultrasonography compared to MRI in therapy monitoring of rheumatoid arthritis patients. AB - PURPOSE: To evaluate wrist and finger joints in patients with rheumatoid arthritis (RA) by grayscale, power Doppler (PD) and contrast-enhanced musculoskeletal ultrasonography (US) and to compare these findings with MRI, clinical (DAS28) and laboratory (ESR; CRP) data. MATERIALS AND METHODS: US was performed at baseline (t0) and after three, six and twelve (t12) months before and after a change of medical treatment. MRI was carried out at t0 and t12 and used as the reference method. Contrast-enhanced US was used to assess one clinically most affected joint region. Different semiquantitative synovitis scores were calculated by grayscale and PD US. RESULTS: Contrast-enhanced US results evaluated by enhancement, slope and semi-quantitative assessment significantly correlated to each other, to grayscale US, CRP, as well as to MRI with the highest correlation coefficients for the used contrast-enhanced US modes (r = 0.56, r = 0.55, r = 0.57; each p < 0.05). Sum scores evaluated by grayscale US showed that synovial inflammation in finger joints was detected significantly more frequently in the palmar aspect than on the dorsal side (p = 0.001). Using power Doppler US, the wrists were significantly more inflamed from dorsal than on the palmar side (p = 0.0004). Significant longitudinal correlations between grayscale and power Doppler US scores were detected. CONCLUSION: Grayscale, power Doppler and contrast-enhanced US are accurate tools for the detection and follow up of synovitis in RA wrist and finger joints, with contrast-enhanced US being most sensitive compared to MRI. All imaging methods reflected a good response to TNFalpha blocking therapy. PMID- 22052063 TI - Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). AB - These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers. PMID- 22052071 TI - Bis- and tris-naphthoimidazolium derivatives for the fluorescent recognition of ATP and GTP in 100% aqueous solution. AB - Naphthoimidazolium groups can form unique ionic hydrogen bonds with anions as imidazolium moieties, and in addition, they are fluorescent, so no further elaborative synthesis is needed to introduce a fluorescent group. In this paper, three naphthoimidazolium derivatives were synthesized and studied for the recognition of nucleotides. Compound 1 composed of a single naphthoimidazolium group and quaternary ammonium group did not show any significant fluorescent changes with various anions and nucleotides, such as ATP, GTP, CTP, TTP, UTP, ADP and AMP. A tripodal compound 3 bearing three naphthoimidazolium groups and three quaternary ammonium groups, respectively, showed large fluorescence enhancements with UTP, CTP and TTP and moderate fluorescence enhancements with ATP and pyrophosphate and a fluorescence quenching effect with GTP. On the other hand, compound 2 bearing two naphthoimidazolium groups and two quaternary ammonium groups displayed a selective fluorescence enhancement with ATP and a selective fluorescence quenching effect with GTP in 100% aqueous solution. PMID- 22052072 TI - The dietary phase 2 protein inducer sulforaphane can normalize the kidney epigenome and improve blood pressure in hypertensive rats. AB - BACKGROUND: Our previous studies have shown that broccoli sprouts high in the glucosinolate glucoraphanin decreases renal and vascular oxidative stress and inflammation as well as blood pressure in spontaneously hypertensive stroke-prone (SHRSP) rats. The objective of this study was to determine whether the metabolite of glucoraphanin, sulforaphane, was responsible for this improved blood pressure and whether this is associated with normalization of renal methylated DNA. METHODS: Sulforaphane was given by gavage to SHRSP and Sprague Dawley (SD) rats over 4 months and blood pressure measured under anesthesia just before euthanasia. Renovascular morphology was determined by histology and methylated deoxycytosine levels analyzed using high-performance liquid chromatography. RESULTS: Mean arterial pressure was 20% higher in vehicle-treated SHRSP when compared to SD. Sulforaphane administration to SHRSP improved blood pressure and lowered this difference to 11%. Vehicle-treated SHRSP had significantly increased wall:lumen ratios in renal arteries, increased numbers of vascular smooth muscle cells (VSMCs), increased renal protein nitration, and decreased (11%) renal DNA methylation compared to SD. Sulforaphane administration to SHRSP significantly lowered arterial wall:lumen ratio by 35%, reduced the number of VSMCs, reduced the level of protein nitration, and increased methylated deoxycytosine levels by 14%. CONCLUSIONS: Sulforaphane administration rectified pathological abnormalities in SHRSP kidneys and significantly improved blood pressure. This was associated with normalization of global kidney DNA methylation suggesting that DNA methylation could be associated with hypertension. PMID- 22052073 TI - Impact of cardiovascular risk factors and inflammatory status on urinary 8-OHdG in essential hypertension. AB - BACKGROUND: The urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) reflect the oxidation status of hypertensive subjects and it can be used for monitoring oxidative stress changes. However, the influence of cardiovascular risk factors and inflammation on the urinary levels of this marker in hypertension (HT) has never evaluated. The purpose of this study was to analyze the impact of cardiovascular risk factors, and established inflammatory markers on 8-OHdG in essential HT. METHODS: We studied 149 asymptomatic hypertensive patients (61 +/- 14 years). A routine physical examination, laboratory analyses, and echo-Doppler study were performed. Urinary 8-OHdG and plasma tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNF-R1), soluble TNF receptor 2 (sTNF-R2), and interleukin-6 (IL-6) were determined. RESULTS: 8-OHdG/creatinine levels were higher in hypertrophic patients (P = 0.022) and correlated with left ventricular mass index (P < 0.01). When 8-OHdG/creatinine was compared according to obesity and diabetes in our hypertensive subjects, no significant differences were found. 8-OHdG/creatinine was increased in hypertensive smokers (P = 0.032) and women (P = 0.006). Furthermore, 8-OHdG/creatinine correlated with TNF-alpha, sTNF-R1, sTNF-R2 (P < 0.0001), and with IL-6 (P < 0.05). A multivariate linear regression analysis showed that gender, smoking, and TNF-alpha were independent factors of 8-OHdG/creatinine. CONCLUSIONS: Urinary 8-OHdG was increased in hypertensive patients with hypertrophy even under medical treatment. The presence of other cardiovascular risk factors on top of HT do not alter the concentrations of this oxidative stress marker, only smoking increasing its levels. TNF-alpha is an independent factor of 8-OHdG. These data suggest that this urinary marker gives specific additional information, further than blood pressure control alone, when evaluating hypertensive patients. PMID- 22052074 TI - High prevalence of prehypertension and hypertension in a working population in Hungary. AB - BACKGROUND: Hungary has one of the highest mortality rates due to strokes among the European Union countries. As elevated blood pressure (BP) is the principal risk factor for strokes, we assessed BP levels, as well as awareness and treatment status of hypertension and prehypertension in a working population sample in Hungary. METHODS: Worksite employees in Budapest and Szeged were screened for their BP using an automated BP measuring instrument (BpTRU). BpTRU readings of heart rate (HR) were also recorded. Respondents were classified as normotensives (NT), prehypertensives (PHTN) and hypertensives (HTN) according to their BP levels, as defined by the JNC 7 guidelines. Body height and body weight were measured and body mass index (BMI) was calculated. Self-reported information regarding smoking was collected. RESULTS: In total, 2,012 respondents were recruited (1,000 white collar; 1,012 blue-collar workers), with a mean (+/-s.d.) age of 34.8 (+/-9.9) years. Of all respondents, 22.6% were identified as HTN and 39.8% as PHTN. Among HTN, 40% were unaware of their condition and only 18.5% were adequately treated. PHTN were similar in age as NT, but showed significantly higher HR. CONCLUSIONS: A high proportion of relatively young and apparently healthy Hungarian employees were diagnosed with prehypertension and hypertension. Only a small proportion of HTN had their BP controlled. BMI and HR were significantly higher among individuals with prehypertension compared to NT. Whether the high rates of hypertension, prehypertension, and low levels of control explain the high stroke mortality and unfavorable cardiovascular disease (CVD) profile of Hungary needs further study. PMID- 22052075 TI - Association of sleep duration and hypertension among US adults varies by age and sex. AB - BACKGROUND: While short sleep duration has been related to hypertension, the impact of age and sex on this association is less well known. We examined the association between hours of sleep and hypertension prevalence among US adults by age and sex. METHODS: The study was conducted using data from the 2007-2009 National Health Interview Surveys (NHISs). The association between self-reported hours of sleep and prevalence of hypertension was assessed after stratifying by age and sex. RESULTS: Among 71,455 participants, age-standardized hypertension prevalence rates (%) were 32.4, 25.5, 22.2, 23.2, 25.5, and 32.5 among adults reporting sleep of <6, 6, 7, 8, 9, and >=10 h/day, respectively (P < 0.001). There was a "U"-shaped association of hours of sleep and hypertension prevalence among all age and sex subgroups. Logistic regression models, using 8 h sleep/day as the referent, showed a greater likelihood of hypertension among those who slept <7 or >=10 h/day after adjusting for sociodemographic, behavior, and health characteristics. Further stratifying by age and sex, while adjusting for all other characteristics, revealed that among adults less than 45 years, short (<6 h for men and <8 h for women) and long (>=10 h for men) sleep were associated with higher likelihood of hypertension. For other age/sex groups, short sleep (<6 h) was associated with higher likelihood of hypertension among middle-aged men and older women, as was long sleep (>=10 h) among middle-aged women. CONCLUSIONS: This national sample study suggests that the association between hours of sleep and hypertension varies by age and sex. PMID- 22052076 TI - Role of AMP-activated protein kinase in alpha-lipoic acid-induced vasodilatation in spontaneously hypertensive rats. AB - BACKGROUND: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has recently emerged as an attractive and novel target for the regulation of vascular smooth muscle contraction. The present study investigated the vasodilatory effects of alpha-lipoic acid (alpha-LA) and the possible mechanism of its action on aortic rings from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: Aortae were removed from WKY and SHR, and contractile responses to acetylcholine and alpha-LA studied in organ chamber. Phosphorylated AMPK (pAMPK), phosphorylated Peutz-Jeghers syndrome kinase LKB1 (pLKB1) and calcium/calmodulin-dependent protein kinase (CaMKK) protein level were measured in SHR, WKY, and aortic smooth muscle (A10) cells. RESULTS: alpha-LA (1-500 umol/l) produced a concentration-dependent relaxation of precontracted aortic rings from 8- and 16-week-old SHR, but not in those from WKY rats. This vasodilatory effect of alpha-LA did not change after preincubation with N(G) nitro-L-arginine methyl ester (100 umol/l), but significantly suppressed by an AMPK inhibitor, compound C (40 umol/l). The expression of pAMPKalpha, pLKB1, and CaMKK were also significantly reduced in endothelium-denuded arteries from 16 week-old SHR compared with those from younger SHR or age-matched WKY rats. After incubation with alpha-LA (100 umol/l), the expression of pAMPKalpha and pLKB1 was significantly increased in the endothelium-denuded aortas from 16-week-old SHR, the expression of CaMKK was more reduced in the endothelium-denuded aortas of 8 week-old SHR, but this was not observed in WKY rats. alpha-LA also activated AMPKalpha phosphorylation in A10 cells. CONCLUSIONS: The effects of alpha-LA on vascular relaxation in SHR result from the enhanced phosphorylation of LKB1-AMPK in aortic smooth muscle. PMID- 22052077 TI - Dosimetric and kinetic investigations of gamma-irradiated sodium tartrate dihydrate. AB - Effects of gamma radiation on solid sodium tartrate dihydrate (NaTA) were studied using electron spin resonance (ESR) spectroscopy. One main singlet located at g = 2.0034 and many weak lines located at low and high magnetic field sides were found in the irradiated samples. Dosimetric and kinetic features of the radical species responsible for the experimental ESR spectra were explored through the variations in the signal intensities with respect to applied microwave power, temperature and storage time. Activation energies of the involved radical species were also determined using data derived from annealing studies. PMID- 22052078 TI - Kinetic modeling of rapid enzymatic hydrolysis of crystalline cellulose after pretreatment by NMMO. AB - Pretreatment of cellulose with an industrial cellulosic solvent, N methylmorpholine-N-oxide, showed promising results in increasing the rate of subsequent enzymatic hydrolysis. Cotton linter was used as high crystalline cellulose. After the pretreatment, the cellulose was almost completely hydrolyzed in less than 12 h, using low enzyme loading (15 FPU/g cellulose). The pretreatment significantly decreased the total crystallinity of cellulose from 7.1 to 3.3, and drastically increased the enzyme adsorption capacity of cellulose by approximately 42 times. A semi-mechanistic model was used to describe the relationship between the cellulose concentration and the enzyme loading. In this model, two reactions for heterogeneous reaction of cellulose to glucose and cellobiose, and a homogenous reaction for cellobiose conversion to glucose was incorporated. The Langmuir model was applied to model the adsorption of cellulase onto the treated cellulose. The competitive inhibition was also considered for the effects of sugar inhibition on the rate of enzymatic hydrolysis. The kinetic parameters of the model were estimated by experimental results and evaluated. PMID- 22052080 TI - Emergency department utilization and capacity. AB - Americans rely on emergency departments (EDs) to play a critical role in the health care safety net. But while the number of ED visits climbed significantly, the number of EDs dropped from 5,000 to 4,000 from 1991 to 2006. This synthesis examines the evidence on who uses EDs, the causes and consequences of overcrowding, and the cost of providing care in the ED. Key findings include: privately insured patients account for the largest and fastest growing segment of ED users. Low income and poor health are strong predictors on ED use. After adjusting for health status and other demographic and market factors, the uninsured use the ED at the same rate as the privately insured, while patients with Medicaid/SCHIP or Medicare had much higher utilization rates. The use of EDs for non-urgent, preventable conditions is growing due to limited access to primary care providers, although the identification of these conditions is imprecise. Patient boarding, or the inability to move patients from the ED to the appropriate inpatient unit, and a shortage of on-call specialists are major causes of ED overcrowding. The true cost of providing care in the ED is complex and not well understood. Finally, expansion of health insurance coverage is likely to increase rather than decrease stress on overcrowded EDs because the insured represent the fastest growing subpopulation of ED users. PMID- 22052079 TI - Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs. AB - AIMS/HYPOTHESIS: Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-beta), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population. METHODS: We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits. RESULTS: The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with beta values of 0.007 (p = 0.05), 0.01 (p = 0.01), 0.007 (p = 0.05), 0.01 (p = 0.003) and 0.08 (p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with beta values of -0.06 (p = 0.04), 0.05 (p = 0.05), -0.08 (p = 0.01) and -0.08 (p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2, ADAM30 and CDKN2A/B, with beta values of 0.05 (p = 0.04), -0.07 (p = 0.03) and -0.08 (p = 0.02), respectively. We also found significant associations of ADAM30 (beta = -0.05; p = 0.01) and CDKN2A/B (beta = -0.05; p = 0.03) with HOMA-beta. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03). CONCLUSIONS/INTERPRETATION: We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification. PMID- 22052081 TI - Imaging human reward processing with positron emission tomography and functional magnetic resonance imaging. AB - Functional neuroimaging (fMRI) studies show activation in mesolimbic circuitry in tasks involving reward processing, like the Monetary Incentive Delay Task (MIDT). In voltammetry studies in animals, mesolimbic dopamine release is associated with reward salience. This study examined the relationship between fMRI activation and magnitude of dopamine release measured with Positron emission tomography study (PET) in the same subjects using MIDT in both modalities to test if fMRI activation is related to dopamine release. Eighteen healthy subjects were scanned with [11C]raclopride PET at baseline and after MIDT. Binding potential (BP(ND)) was derived by equilibrium analysis in striatal subregions and percent change across conditions (?BP(ND)) was measured. Blood oxygen level dependence (BOLD) signal changes with MIDT were measured during fMRI using voxelwise analysis and ROI analysis and correlated with ?BP(ND). ?BP(ND) was not significant in the ventral striatum (VST) but reached significance in the posterior caudate. The fMRI BOLD activation was highest in VST. No significant associations between ?BP(ND) and change in fMRI BOLD were observed with VST using ROI analysis. Voxelwise analysis showed positive correlation between BOLD activation in anticipation of the highest reward and ?BP(ND) in VST and precommissural putamen. Our study indicates that endogenous dopamine release in VST is of small magnitude and is related to BOLD signal change during performance of the MIDT in only a few voxels when rewarding and nonrewarding conditions are interspersed. The lack of correlation at the ROI level may be due to the small magnitude of release or to the particular dependence of BOLD on glutamatergic signaling. PMID- 22052082 TI - Do medical homes reduce disparities in receipt of preventive services between children living in immigrant and non-immigrant families? AB - The patient-centered medical home model has the potential to reduce healthcare disparities among immigrant children. The purpose of this study is to examine the relationship between medical home (MH) participation and receipt of preventive services among immigrant children age 0-17. The study employed extant data from the National Survey of Children's Health, 2007 (NSCH). Logistic regression analyses were employed to assess the relationship between receipt of preventive services and MH status among immigrant and non-immigrant children. Due to primarily the lack of family-centered care, only 40% of immigrant children met the medical home criteria versus approximately 62% of non-immigrant children. Immigrant children have decreased odds of receiving preventive care despite MH status. Improving the family-centered care aspect of the MH is necessary to increasing medical home access to immigrant children and the receipt of preventive services for immigrant children who meet the MH criteria. PMID- 22052083 TI - Development of educational materials to improve rates of early eye care for Hispanic children. AB - The purpose of this study was to develop targeted materials to encourage Hispanic parents to seek eye care for their children. Hispanic children present with high rates of eye problems such as astigmatism, strabismus, and amblyopia. Related vision impairment can be prevented with timely detection and treatment. After failing a vision screening, a child must obtain professional eye care to take care of the suspected problem. We involved Hispanic community members and health care experts in Alabama to develop educational materials to encourage Hispanic parents to seek eye care for their children. There were six stages in the development of the educational materials: (a) focus groups with Hispanic parents, (b) development of preliminary materials (c) panel with Hispanic health experts (d) panel with members of the target population (e) final production of materials (f) pilot testing of materials. The parents and health experts suggested the information should be provided in the form of radio announcements, brochures, and newspaper advertisements. They also noted the content should stress the importance of seeking vision care for children even when there were no visible problems. Materials developed through this project included messages designed to overcome specific barriers identified by Hispanic parents and to educate them on the importance of comprehensive eye care for all children, regardless of the presence of visible symptoms. PMID- 22052084 TI - Longitudinal stent deformation: a retrospective analysis of frequency and mechanisms. AB - AIMS: Modern drug-eluting stents are constructed with thin struts and are easy to deliver and highly conformable. However, although innovative designs have enabled maintenance of radial strength, longitudinal strength may be lower with these stents and there have been recent reports of longitudinal stent compression of ostially deployed stents. We report the experience in our centre on longitudinal stent deformation and explore mechanisms of this complication and its frequency with various drug-eluting stent platforms. METHODS AND RESULTS: Nine cases of longitudinal stent deformation were identified over a four year period representing 0.2% of cases and affected 0.097% of stents deployed. There were several mechanisms for this complication including compression by post-dilatation balloons, guide catheter extensions and proximal embolic protection devices. The rate of stent deformation varied from 0% in several stent types to 0.86% in the case of the Promus Element stent. There was one case of late stent thrombosis attributable to longitudinal stent deformation. CONCLUSIONS: Longitudinal stent deformation can occur secondary to a variety of mechanisms and identification is important as, left untreated, it may be associated with a risk of stent thrombosis. Although seen with several different stents, in our series it was more commonly observed with the Promus Element stent. PMID- 22052085 TI - The role of CH-pi interaction in the charge transfer properties in tris(8 hydroxyquinolinato)aluminium(III). AB - The charge mobility is a key property in many electro-optical materials, with charge transfer (CT) taking place in a solid matrix of molecules. Large intermolecular electronic interaction is one of the key factors for a good CT rate, which is dependent on both intra- and intermolecular structures. The connection of the molecular structure with the intermolecular CT property would facilitate the search for a new material with desirable CT property, but currently it is still quite limited by the lack of knowledge for intermolecular configurations. In the present work, we study factors influencing the intermolecular configurations, and subsequently the CT property, in tris(8 hydroxyquinolinato) aluminium(III) (AlQ(3)) from all currently available crystal structures. We found that there exists a pair of CH-pi interactions in a good majority of the pi-pi stacked bimolecular configurations. Such CH-pi and pi-pi interacting structures are also seen in the crystal structures of many other similar molecules. With both experimental and simulated structures, we show that the CH-pi interaction stabilizes the bimolecular configurations, and drives the structure towards a region with a higher electron transfer coupling and lower hole transfer coupling. This effect likely affects the electron transport property of AlQ(3), since it is consistent with recent experimental results, where AlQ(3) analogs with their CH-pi interaction blocked either require a higher operating voltage in light-emitting devices [Sapochak et al., J. Am. Chem. Soc., 2001, 123, 6300], or become bipolar in their charge mobilities [Liao et al., J. Am. Chem. Soc., 2009, 131, 763]. CH-pi interaction is commonly seen in aromatic molecules, which are frequently used as building blocks in molecules for electro optical applications. Our work points out a possible way to enhance the desired CT property in the design of new materials. PMID- 22052087 TI - Transport of nanoparticles through the placental barrier. AB - Nanoparticles (NP) are organic or inorganic substances, the size of which ranges from 1 to 100 nm, and they possess specific properties which are different from those of the bulk materials in the macroscopic scale. In a recent decade, NP were widely applied in biomedicine as potential probes for imaging, drug-delivery systems and regenerative medicine. However, rapid development of nanotechnologies and their applications in clinical research have raised concerns about the adverse effects of NP on human health and environment. In the present review, special attention is paid to the fetal exposure to NP during the period of pregnancy. The ability to control the beneficial effects of NP and to avoid toxicity during treatment requires comprehensive knowledge about the distribution of NP in maternal body and possible penetration through the maternal-fetal barrier that might impair the embryogenesis. The initial in vivo and ex vivo studies imply that NP are able to cross the placental barrier, but the passage to the fetus depends on the size and the surface coating of NP as well as on the experimental model. The toxicity assays indicate that NP might induce adverse physiological effects and impede embryogenesis. The molecular transport mechanisms which are responsible for the transport of nanomaterials across the placental barrier are still poorly understood, and there is a high need for further studies in order to resolve the NP distribution patterns in the organism and to control the beneficial effects of NP applications during pregnancy without impeding the embryogenesis. PMID- 22052086 TI - Promoter methylation and tissue-specific transcription of the alpha7 nicotinic receptor gene, CHRNA7. AB - The alpha7 nicotinic acetylcholine receptor is known to regulate a wide variety of developmental and secretory functions in neural and non-neural tissues. The mechanisms that regulate its transcription in these varied tissues are not well understood. Epigenetic processes may play a role in the tissue-specific regulation of mRNA expression from the alpha7 nicotinic receptor subunit gene, CHRNA7. Promoter methylation was correlated with CHRNA7 mRNA expression in various tissue types and the role of DNA methylation in regulating transcription from the gene was tested by using DNA methyltransferase (DNMT1) inhibitors and methyl donors. CHRNA7 mRNA expression was silenced in SH-EP1 cells and bisulfite sequencing PCR revealed the CHRNA7 proximal promoter was hypermethylated. The proximal promoter was hypomethylated in the cell lines HeLa, SH-SY5Y, and SK-N-BE which express varying levels of CHRNA7 mRNA. Expression of CHRNA7 mRNA was present in SH-EP1 cells after treatment with the methylation inhibitor, 5-aza-2 deoxycytidine (5-Aza-CdR), and increased in SH-EP1 and HeLa cells using another methylation inhibitor, zebularine (ZEB). Transcription from the CHRNA7 promoter in HeLa cells was increased when the methyl donor methionine (MET) was absent from the media. Using methylation-sensitive restriction enzyme analysis (MSRE), there was a strong inverse correlation between CHRNA7 mRNA levels and promoter DNA methylation across several human tissue types. The results support a role for DNA methylation of the proximal promoter in regulation of CHRNA7 transcription. PMID- 22052088 TI - Interleukin-28B genotypes determine response to pegylated-interferon plus ribavirin therapy in patients with hepatitis C virus infection. AB - We recently reported that the interleukin (IL)-28B major genotype is a predictor of early suppression of the hepatitis C virus (HCV) at 12 weeks in response to pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy. The present study investigated the relationship between IL-28 genotypes and the virological response to PEG-IFN/RBV therapy at 24 and 48 weeks. Genotypes of the IL-28B rs8099917 T>G single nucleotide polymorphism were determined in 177 patients with HCV infection. Among them, 56 patients with HCV1 infection were treated with PEG IFN/RBV. The frequency of the IL-28B major allele (TT) was 73.8% in patients with HCV serotype 1 and 86.3% in patients with HCV serotype 2. The rate of HCV-RNA positivity was significantly lower at 48 weeks in patients with the IL-28B major allele compared to patients with the IL-28B minor allele (TG or GG). The rate of HCV-RNA positivity at 24 weeks tended to be lower in patients with the IL-28B major allele, but there was no statistical significance (P=0.059). The sustained virological response (SVR) rate was 45.9% in patients with the IL-28B major allele, but 13.3% in patients with the IL-28B minor allele. The SVR correlated with the IL-28B major allele (OR=7.13, P=0.010), early virological response (OR=33.3, P=0.008), HCV-RNA <= 6.3 log IU/ml (OR=81.2, P=0.009) and gamma-GTP <= 47 IU/l (OR=49.4, P=0.027). The IL-28B genotype is a significant pre-treatment predictor of the response to PEG-IFN/RBV therapy at 48 weeks in patients with HCV infection. PMID- 22052089 TI - Using the Agency for Healthcare Research and Quality patient safety indicators for targeting nursing quality improvement. AB - Quantifying the critical impact nurses have on the prevention and early recognition of potential complications and adverse events, such as those identified by the Agency for Healthcare Research and Quality (AHRQ) patient safety indicators (PSI), is becoming increasingly important. In this paper, we describe how the AHRQ PSI may be used to identify nursing-specific opportunities to improve care based on data from the national AHRQ PSI validation pilot project. PMID- 22052090 TI - Understanding prenatal health care for American Indian women in a Northern Plains tribe. AB - Early and regular prenatal care appointments are imperative for the health of both the mother and baby to help prevent complications associated with pregnancy and birth. American Indian women are especially at risk for health disparities related to pregnancy and lack of prenatal health care. Previous research has outlined a basic understanding of the reasons for lack of prenatal care for women in general; however, little is known about care received by pregnant women at Indian Health Service hospitals. Qualitative interviews were carried out with 58 women to better understand the prenatal health experiences of American Indian women from one tribe in the Northern Plains. Several themes related to American Indian women's prenatal health care experiences were noted, including communication barriers with physicians, institutional barriers such as lack of continuity of care, and sociodemographic barriers. Solutions to these barriers, such as a nurse midwife program, are discussed. PMID- 22052091 TI - Perceptions of health and well-being held by Native Hawaiian migrants. AB - BACKGROUND AND PURPOSE: Migration is often a challenging process. Native Hawaiians migrate from Hawaii to Las Vegas at an impressive rate, but no research has explored how migration affects their health and well-being. The purpose was to describe how Native Hawaiians in Las Vegas perceive their health and well being and any changes therein since migrating. DESIGN: Using a qualitative descriptive design, 27 participants took part in semistructured interviews. FINDINGS: Most participants perceived no changes in health and minor changes in well-being. Many maintained their well-being by adapting valued activities to their new circumstances. However, 5 participants were deeply burdened by life in Las Vegas or longing for Hawaii, and their well-being suffered. They tended to identify barriers to well-being rather than ways to foster it. CONCLUSION: Health care providers can help Native Hawaiian migrants by encouraging early access to the health care system in their new location and facilitating participation in helpful, adaptive behaviors. PMID- 22052092 TI - Evaluating the influence of cultural competence education on students' transcultural self-efficacy perceptions. AB - Guided by the cultural competence and confidence (CCC) model, the Transcultural Self-Efficacy Tool (TSET) was used to evaluate the influence of cultural competence education on the transcultural self-efficacy (TSE) perceptions of undergraduate nursing students following an integrated approach to cultural competence education. Results continue to support that TSE is influenced by formalized education and other learning experiences. As hypothesized, compared with novice students, advanced students' scores were higher for all subscales in both cross-sectional (n = 147) and longitudinal (n = 36) study designs. Results from analysis of variance and covariance demonstrated that none of the demographic variables predicted change; semester was the sole predictor, lending additional support that (a) the educational interventions throughout the four semesters influenced TSE changes and (b) all students regardless of background benefit (and require) formalized cultural competence education. Implications for nurse educators conclude the article. PMID- 22052093 TI - Perceived acceptance of condom use by partners, close friends, and parents of Spanish and Mozambican heterosexual adolescents. AB - PURPOSE: The main aim of the current study was to compare Spanish and Mozambican male and female secondary students, with regard to sexual behaviors and perceptions surrounding the acceptance of condom use. METHOD: The participants were 773 secondary students-412 from Spain and 361 from Mozambique, aged from 15 to 17 years old. Data collection was done using questionnaires. Analysis was carried out using multivariate methods. RESULTS: Spanish adolescents took more precautions than Mozambican adolescents. Furthermore, Spanish adolescents perceived that the acceptance of condom use by their referents were higher than those reported by the Mozambican adolescents. Among Spanish youths, only the perceived acceptance of their current partner predicted condom use in their most recent sexual encounter. DISCUSSION: Differences in the decision-making power of males and females and the type of partner might explain the differences observed in the preventive behavior of the students in both countries. PMID- 22052094 TI - Well-being in Dinka refugee women of southern Sudan. AB - The purpose of this study was to understand the health and well-being of Sudanese refugee women who were resettled with their children to the United States. The design was an interpretive ethnography using individual interviews and participant observation with extensive field notes. The findings describe personal factors as well as community and social conditions that influenced the health and well-being of the refugee women and their families. These influences are captured in the three themes that emerged from the study: (1) liminality- living between two cultures, (2) self-support--standing on our own two legs, and (3) hope for the future. These themes describe a process of how refugee women achieve well-being in the transition to a new country and culture. The study contributes to our theoretical understanding of how to develop culturally congruent interventions for resettled refugees. PMID- 22052095 TI - Somali immigrant women's health care experiences and beliefs regarding pregnancy and birth in the United States. AB - PURPOSE: To describe Somali immigrant women's health care experiences and beliefs regarding pregnancy and birth. DESIGN: Four focus group interviews were conducted using a convenience sample of Somali women who were pregnant or had recently delivered. Qualitative thematic content analysis was used. FINDINGS: Six major themes emerged: pregnancy as a natural experience for women, value and relevance of prenatal care, lack of control and familiarity with delivery in the United States, balancing the desire to breastfeed with practical concerns and barriers, discomfort with mental health issues, and challenges in the healthcare system. DISCUSSION: Somali immigrant women perceive, interpret, and react to Western health practices from a perspective that includes their cultural, religious, and "scientific" beliefs. IMPLICATIONS: Implications include cultural competency workshops. Educational materials and prenatal education sessions that support the women's needs have been developed for this population and should be a focus of future research. PMID- 22052096 TI - Perspectives of nursing faculty about nursing in Iraq. AB - PURPOSE: Long standing problems are apparent in professional nursing in Iraq. This is a critical point in time and feedback and input from nurses will be important in advancing the profession. DESIGN: A questionnaire was used to explore the attitudes of faculty members about professional nursing, women's roles and nursing, and the Iraqi Nurses Association. The questionnaire was administered to 31 faculty members at the College of Nursing, University of Baghdad. FINDINGS: The respondents reported the poor image of Iraqi nursing and the relationship between physicians and nurses as the most immediate problems facing the profession. The respondents are not active in their professional association and believe that the association is not addressing current problems. Profound changes are needed in professional nursing before nurses can play significant roles in the Iraqi health care system. PMID- 22052097 TI - [Substrate specificity of extended spectrum beta-lactamases CTX-M isolated from intensive care pacients in Faculty Hospital in Ostrava and in Regional Hospital T. Bata in Zlin]. AB - OBJECTIVE: Evaluation of kinetic parameters isolated extended spectrum beta lactamases and evaluation of their substrate specifities. MATERIALS AND METHODS: Fourty strains of Escherichia coli with evidence of producing extended spectrum beta-lactamases (ESBLs) and their designated type by polymerase chain reaction and sequencing was used in the study. Strains were stored in bacteriological collection at the Department of Microbiology Teaching Hospital and Palacky University and originated from clinical specimens of ICU, Faculty Hospital Ostrava and Regional Hospital of T. Bata patients. Strains were collected from hospitalized patients in one year (1. 1. 2009 - 31. 12. 2009). The isolated enzymes were used for spectrofotometric measurement of specific activities by hydrolysis of antibiotics. Beta-lactamases of the six selected strains were purified and used for the measurement of other kinetic parameters. RESULTS: Measurement of specific activities in lysates with partially purified enzyme (beta-lactamases CTX-M-15 or CTX-M-27) showed that the best hydrolyzed antibiotic was cefazolin. Extended spectrum beta-lactamase-type CTX-M-15 had the highest affinity for cefoperazon, the highest catalytic efficiency and high hydrolytic efficiency against cefazolin. The values of kinetic parameters of purified type ESBLs CTX-M-27 was slightly different between strains and showed a high efficiency against cefoperazone and cefuroxime, high hydrolytic activity against cefazolin and strong catalytic effeciency against cefazolin and cefotaxime. CONCLUSION: Comparison of the measured data enabled to evaluate cefazolin as the best substrate for used ESBLs. The studied enzymes showed very strong hydrolytic activity and catalytic efficiency against cefazolin. PMID- 22052098 TI - [Effect of excipients on the preparation and properties of antibiotic solution for intravenous application]. AB - OBJECTIVE: To evaluate the effect of excipients disodium-edetate dihydrate and citric acid monohydrate on rate of antibiotic powder dissolution, particle size after dissolution and chemical stability of the product after reconstitution with water for injection and 5% glucose solution. MATERIAL AND METHODS: The product containing excipients (Tazocin) was compared with generic products without excipients. Rate of dissolution was evaluated organoleptically and spectrophotometrically, particle size was determined microscopically after reconstitution and after 4 hours of standing at laboratory temperature and chemical stability was assessed by HPLC. RESULTS: Tazocin dissolved significantly faster in both solvents compared to products without excipients (3-4 min versus 10-13 min). The limit for maximal number of particles larger than 25 mm in the reconstituted solution was not exceeded in any of the products either after using water for injection or after using 5% glucose, both after reconstitution and after 4 hours of standing at laboratory temperature. Nevertheless, only for Tazocin the number of unwanted larger particles decreased in time in both solvents. Disodium-edetate dihydrate and citric acid stabilized the dissolved particles of the active substance and prevented its transformation into the insoluble form, which results in lower number of unwanted large particles. Tazocin was more stable, but the stability was not significantly better than its generic products. CONCLUSIONS: Disodium-edetate dihydrate and citric acid monohydrate (and possibly the used method of lyophilisation) therefore have a positive effect on the preparation and properties of antibiotic solution for intravenous application. PMID- 22052099 TI - [Virulence factors in Proteus spp. bacteria isolated from urinary tract infections: their detection and importance]. AB - Nosocomial infections associated with biofilm formation have been a serious problem in recent years. Up to 32 % of them are urinary tract infections in patients with long-dwelling catheters. Catheters represent an ideal surface for bacterial adhesion, facilitating easier colonization of the urinary tract. Important pathogens causing these infections are bacteria of the genus Proteus that colonize catheters not only by biofilm formation but also using other virulence factors. Those were developed for survival in the host organism and are also used by bacteria to infect the host or fight the defence mechanisms. The study focused on the following selected virulence factors: swimming, swarming and twitching motility, swarming motility across various types of urinary catheters, biofilm formation in various media, formation of biofilm on catheters, haemolysin and urease production. A total of 102 strains isolated from urinary catheters and 50 strains isolated from stools were analyzed. In twitching motility, a difference between strains isolated from catheters and stools was statistically significant (p = 0.012). In swimming and swarming motility, the difference was not significant (p = 0.074 and p = 0.809, respectively). In motility across various catheter types, a statistically significant difference was found in strains isolated from both catheters and stools (p " 0.01 in both cases). For biofilm formation analyses, BHI and BHI with 4 % glucose were used. In BHI, biofilm was produced by all strains, with 65% of catheter strains and 88 % of strains from stools being strong producers. Similarly, all strains produced biofilm in BHI with 4 % glucose, with strong producers in 94 % and 92 % of strains isolated from catheters and stools, respectively. In formation of biofilm on catheters, there was a statistical difference between strains from catheters and stools (p = 0.00008). All strains isolated from both catheters and stools produced urease; no difference in urease production was statistically significant (p = 0.653). On agar with washed sheep erythrocytes, haemolysin production was not detected in any of the isolated strains. The quantitative method using horse erythrocytes revealed haemolysis production in three strains isolated from catheters. PMID- 22052100 TI - [Pneumonia-causing bacterial pathogens in intensive care patients]. AB - BACKGROUND: This prospective study aimed at determining etiologic agents causing nosocomial pneumonia in a precisely defined group of patients and resistance of bacterial pathogens to antimicrobial drugs. MATERIAL AND METHODS: The study comprised patients hospitalized at the Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Palacky University and University Hospital Olomouc who developed pneumonia. From those patients, secretion samples were collected for microbiological analysis. RESULTS: A total of 77 secretion samples from 51 patients were analyzed. Of 90 isolates, 71 were classified as etiologic agents, with the most frequently isolated strains being those of Klebsiella pneumoniae (32 %), Pseudomonas aeruginosa (22 %), Burkholderia cepacia complex (10 %) and Escherichia coli (8 %). The highest proportions of multiresistant strains were found in Pseudomonas aeruginosa (56 %), Klebsiella pneumoniae (52 %), Escherichia coli (25 %) and Burkholderia cepacia complex (100 %). Pairs of identical strains were detected in five cases (3x Klebsiella pneumoniae and 2x Pseudomonas aeruginosa). In Burkholderia cepacia complex, the same strain was identified in four out of five cases. Eighteen patients died during hospitalization. CONCLUSION: Most isolates were single strains and hospital acquired pneumonia may be characterized as endogenous. Four identical cultures of Burkholderia cepacia complex were classified as Burkholderia multivorans by the MALDI-TOF system and clonal spread of this strain may be assumed. PMID- 22052101 TI - [The proof of antineural antibodies in patients with neuroborreliosis]. AB - The study has been performed on the proof of anti-neural antibodies in patients with early form of neuroborreliosis (NB). The presence of anti-ganglioside and anti-myelin associated glykoprotein (MAG) antibodies were tested in serum by the commercial western-blotting kits. Forty serum samples from 38 patients were examined (17 patients with facial palsy, 12 Bannwarth's syndrome, 4 multiple cranial neuritis, 5 other radiculopathies), but only one sample was found positive (for anti-GM3 antibodies). It could be concluded, that anti-ganglioside and anti-MAG antibodies are only sparsely present in the early NB. PMID- 22052102 TI - Influence of initial metabolic rate on the power-duration relationship for all out exercise. AB - A single 3-min all-out cycling test can be used to estimate the power asymptote (critical power, CP) and the curvature constant (W') of the power-duration relationship for severe-intensity exercise. It was hypothesized that when exercise immediately preceding the 3-min all-out test was performed CP would systematically reduce the W' without affecting the CP. Seven physically active males completed 3-min all-out cycling tests in randomized order immediately preceded by: unloaded cycling (control); 6-min moderate; 6-min heavy; 2-min severe (S2); or 4-min severe (S4) intensity exercise. The CP was estimated from the mean power output over the final 30 s of the test and the W' was estimated as the power-time integral above end-test power. There were no significant differences in the CP between control (279 +/- 62), moderate (275 +/- 52), heavy (286 +/- 66 W), S2 (274 +/- 55), or S4 (273 +/- 65 W). The W' was significantly lower (P < 0.05) in S2 (11.5 +/- 2.5) and S4 (8.9 +/- 2.2) than in control (16.3 +/- 2.3), moderate (17.2 +/- 2.4) and heavy (15.6 +/- 2.3 kJ). These results support the notion that the W' is predictably depleted only at a power output >CP whereas the CP is independent of the mechanisms which reduce W'. PMID- 22052103 TI - Muscular strength and markers of insulin resistance in European adolescents: the HELENA Study. AB - The aim of the study was to examine the association of muscular strength with markers of insulin resistance in European adolescents. The study comprised a total of 1,053 adolescents (499 males; 12.5-17.5 years) from ten European cities participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Cross-Sectional Study. Muscular strength was measured by the handgrip strength and standing long jump tests. Cardiorespiratory fitness was measured by the 20-m shuttle run test. Fasting insulin and glucose were measured and the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) indices were calculated. Weight, height, waist circumference and skinfold thickness were measured, and body mass index (BMI) was calculated. In males, the handgrip strength and standing long jump tests were negatively associated with fasting insulin and HOMA (all P < 0.05) after controlling for pubertal status, country and BMI or waist circumference. When skinfold thickness was included in the model, the association became non-significant. In females, the standing long jump test was negatively associated with fasting insulin and HOMA (all P < 0.001) after controlling for pubertal status, country and surrogate markers of total or central body fat (BMI, waist circumference or skinfold thickness). Findings were retained in males, but not in females after controlling for cardiorespiratory fitness. The findings of the present study suggest that preventive strategies should focus not only on decreasing fatness and increasing cardiorespiratory fitness but also on enhancing muscular strength. PMID- 22052104 TI - P.O.P.A. study: prevention of postoperative abdominal adhesions by icodextrin 4% solution after laparotomy for adhesive small bowel obstruction. A prospective randomized controlled trial. AB - BACKGROUND: Adhesive small bowel obstruction (ASBO) is an important cause of hospital admission, is associated with significant morbidity and mortality, and therefore is a substantial burden for healthcare systems worldwide. Icodextrin 4% solution (Adept, Shire Pharmaceuticals, UK) is a high-molecular-weight a-1,4 glucose polymer approved in Europe for use as intraoperative lavage and postoperative instillation to reduce the occurrence of post-surgery intra abdominal adhesions. The present clinical study aimed to evaluate the safety and effectiveness of icodextrin 4% in decreasing the incidence, extent, and severity of adhesions in patients after abdominal surgery for ASBO. METHODS: The study was a single-center prospective, randomized investigation. The study is designed and conducted in compliance with the principles of Good Clinical Practice regulations. Safety and efficacy of icodextrin 4% in the study group are compared to no anti-adhesion treatment in a parallel control group with blinded evaluation of primary endpoints. Primary endpoints are the evaluation of the therapeutic role of icodextrin 4% in reducing ASBO recurrence incidence and the need of laparotomies for ASBO recurrence, as well as adhesion formation (with evaluation of their incidence, extent, and severity). A sum of 181 patients with ASBO and surgical indication to laparotomy were enrolled and randomized in two groups. Patients were submitted to adhesiolysis with bowel resection if required with or without anastomosis. The first group received traditional treatment (control group), whereas the second group was treated with the addition of icodextrin 4% solution before the abdominal closure. RESULTS: Ninety-one patients were randomized to have icodextrin 4% solution administered intraperitoneally, and 90 patients were randomized to have the traditional treatment. The two study groups were homogeneous regarding their baseline characteristics. The ASBO recurrence rate was 2.19% (2/91) in the icodextrin groups vs 11.11% (10/90) in the control group after a mean follow-up period of 41.4 months (p < 0.05). No differences were found in the need of laparotomies for ASBO recurrence in the studied groups. The adhesion severity score seems lower in the group treated with the addition of icodextrin (p = n.s.). CONCLUSIONS: The data resulting from this RCT showed that the use of icodextrin 4% solution in ASBO is safe and reduces intra-abdominal adhesion formation and the risk of re-obstruction. PMID- 22052105 TI - Robotic surgery for rectal cancer: initial experience from 30 consecutive patients. AB - BACKGROUND: Robotic surgery offers 3D visualization and the advantage of the usage of multi-articulated instruments with superior dexterity. Theoretically, it can overcome many limitations of laparoscopic rectal surgery in the narrow pelvis. MATERIALS AND METHODS: Between January 2010 and January 2011, the patients who underwent robotic rectal resection for cancer were retrospectively evaluated in terms of demographics, operative data, complications, the duration of hospital stay, and histopathological data. RESULTS: Thirty consecutive patients made up of 13 female and 17 male patients underwent robotic rectal resection. Sphincter-saving mesorectal excision was performed in 27 patients. Of these, there were 19 total and 8 partial mesorectal excisions. The mean operative time was 270 min (175-480 min). The median postoperative hospital stay was 4 days (4-20 days). No operation was converted. The complication rate was 13.3%. One patient died due to colonic necrosis caused by Drummond artery deficiency (3.3%). The median number of harvested lymph nodes was 15 (3-38), and the distal resection margin was 4 cm (2-8). Histopathological evaluation revealed that the mesorectum resection was complete in all patients. CONCLUSION: Robotic rectal surgery (hybrid or totally robotic) is a safe and feasible procedure when performed by experienced laparoscopic surgeons. PMID- 22052106 TI - RAGE gene deletion inhibits the development and progression of ductal neoplasia and prolongs survival in a murine model of pancreatic cancer. AB - BACKGROUND: The receptor for advanced glycation end-products (RAGE) is implicated in pancreatic tumorigenesis. Activating Kras mutations and p16 inactivation are genetic abnormalities most commonly detected as pancreatic ductal epithelium progresses from intraepithelial neoplasia (PanIN) to adenocarcinoma (PDAC). OBJECTIVE: The aim of this study was to evaluate the effect of RAGE (or AGER) deletion on the development of PanIN and PDAC in conditional Kras ( G12D ) mice. MATERIALS AND METHODS: Pdx1-Cre; LSL-Kras ( G12D/+) mice were crossed with RAGE ( /-) mice to generate Pdx1-Cre; LSL-Kras ( G12D/+) ; RAGE (-/-) mice. Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-) mice were crossed with RAGE (-/-) mice to generate Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice. Pancreatic ducts were scored and compared to the relevant RAGE (+/+) controls. RESULTS: At 16 weeks of age, Pdx1-Cre; LSL-Kras ( G12D/+); RAGE (-/-) mice had significantly fewer high-grade PanIN lesions than Pdx1-Cre; LSL-Kras ( G12D/+); RAGE (+/+) controls. At 12 weeks of age, none of the Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice had PDAC compared to a 45.5% incidence of PDAC in Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (+/+) controls. Finally, Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice also displayed markedly longer median survival. CONCLUSION: Loss of RAGE function inhibited the development of PanIN and progression to PDAC and significantly prolonged survival in these mouse models. Further work is needed to target the ligand-RAGE axis for possible early intervention and prophylaxis in patients at risk for developing pancreatic cancer. PMID- 22052108 TI - Evaluation of upper and lower gastrointestinal histology in patients with ileal pouches. AB - BACKGROUND: Inflammatory complications of ileal pouch-anal anastomosis (IPAA), including pouchitis and Crohn's disease (CD) of the pouch, are common in patients with restorative proctocolectomy for ulcerative colitis. It is not clear whether these inflammatory conditions can affect upper GI tract. The aim of the study was to evaluate correlation between duodenal and pouch histology in patients with healthy and diseased pouches. METHODS: All IPAA patients who had esophagogastroduodenoscopy with biopsy after colectomy (N = 96) were included. H&E slides of gastric, duodenal, neo-terminal ileum, and pouch body biopsies were blindly re-reviewed by an expert GI pathologist for acute and chronic inflammation. Demographic and clinical variables and pouch outcome were analyzed. RESULTS: There was a significant correlation between acute inflammation in the duodenum as measured by neutrophil infiltration score and the presence of chronic pouchitis (kappa coefficient = 0.21, P < 0.05). Intraepithelial lymphocytosis of the duodenum, though uncommon, only occurred in patients with irritable pouch syndrome, chronic pouchitis, or CD of the pouch. Crypt distortion of duodenal epithelium was only seen in patients with inflammatory or structural diseases of the pouch, including acute (18.2%) and chronic (5%) pouchitis, CD of the pouch (14.3%), and surgical complications of the pouch (14.4%). CONCLUSION: Histologic evaluation of duodenal biopsy may provide additional information in patients with ileal pouches, as patients with normal histology of the pouch may have an abnormal duodenal histology. PMID- 22052107 TI - AIB1 as an independent prognostic marker in hepatocellular carcinoma after hepatic resection. AB - BACKGROUND: Amplified in breast cancer 1 (AIB1) has been shown to promote growth and invasion in several types of human cancers and to have a prognostic role in some of cancers. However, its prognostic significance in hepatocellular carcinoma (HCC) remains unknown. This study aimed to address the issue. METHODS: Immunohistochemical staining of AIB1 was performed for HCC and paired paratumorous liver (PTL) tissues from 139 patients. Associations between AIB1 expression with clinicopathological variables and patient survival were evaluated. RESULTS: The expression rate of AIB1 was significantly higher in HCC (71/139, 51.1%) than in PTL tissues (1/139, 0.72%, P < 0.001). AIB1 expression in HCC was significantly associated with serum alpha-fetoprotein levels (P = 0.001) and Edmondson-Steiner grade (P = 0.038). Higher AIB1 expression in HCC was associated with shorter cumulative overall survival of the patients. Multivariate Cox regression analysis revealed that AIB1 was of independent prognostic significance for HCC. CONCLUSIONS: AIB1 is independently associated with poor prognosis of HCC. PMID- 22052109 TI - Lymphangioma of the gallbladder in adults: review of the literature and a case report. AB - INTRODUCTION: Lymphangiomas of the gallbladder in adults are extremely rare with only 10 cases published worldwide to date. CASE PRESENTATION: We herein report a case of a 26-year-old male who presented with abdominal right upper quadrant pain, nausea, vomiting, and diarrhea. An ultrasound, computer tomography scan, and magnetic resonance imaging showed a cystic mass interposed between the gallbladder and the liver with characteristics identical to those of lymphangiomas in more common locations. The patient underwent an open excision of the large spongy mass en bloc with the gallbladder. CONCLUSION: Histological findings confirmed the diagnosis of lymphangioma. Also, we provide a review of 10 cases presented in the literature, with a discussion of the clinical features, diagnosis, and surgical approach. PMID- 22052110 TI - From coverage to care. AB - An important determinant of access is whether people have a usual source of care. Health insurance coverage is one factor that makes people more likely to have a usual provider, but coverage alone does not guarantee access. This synthesis examines the relationship between health insurance and having a regular care provider. Results indicate people with health insurance are more likely to have a usual source of care; the newly insured, as well as people with unstable coverage are less likely to have a regular source of care; and about two-thirds of those without a usual source of care say the main reason they have no such source is because they rarely get sick. Among those who have a usual source of care, most see an office-based doctor as their primary provider. The uninsured and publicly insured are more likely to use an institution and to face access barriers. PMID- 22052111 TI - Survivin T9809C, an SNP located in 3'-UTR, displays a correlation with the risk and clinicopathological development of hepatocellular carcinoma. AB - BACKGROUND: Early detection of hepatocellular carcinoma (HCC) is seldom available because of the lack of reliable markers. Survivin is an anti-apoptotic protein that is implicated in the regulation of apoptosis and cell cycle, and it is undetectable in normal adult tissues but is overexpressed in various types of cancers. Survivin is thus commonly considered to be a marker of malignancy. The aim of this study was to explore the association between survivin gene polymorphisms and the risk and diagnostic progress of HCC. METHODS: A total of 135 patients with HCC and 496 healthy control subjects were recruited. Five single nucleotide polymorphisms (SNPs) of survivin genes were determined by real time polymerase chain reaction (real-time PCR) and further analyzed statistically. RESULTS: We first found that the -241 C/T and -235 G/A genetic polymorphisms of survivin did not occur frequently enough or even lacked in Taiwanese population. The +9809 C/C polymorphism exhibited a significant (P < .05) low risk of 0.525-fold (95% confidence interval [95% CI] = 0.297-0.930) to have HCC compared with the wild-type homozygotes and a low ratio of 0.214-fold (95% CI = 0.051-0.890) for positive anti-HCV was shown in the individuals with survivin +9809 polymorphic CC allele compared with the TT/TC genotypic subgroup. CONCLUSIONS: Survivin +9809 polymorphic genotype is associated with the risk of HCC, and the HCC patients with survivin +9809 CC homozygotes might have a low risk of developing infected HCV-dependent HCC. The results suggest that the survivin T9809C SNP might contribute to the prediction of susceptibility and pathological development to HCC. PMID- 22052112 TI - Myxoid?round cell liposarcoma (MRCLS) revisited: an analysis of 418 primarily managed cases. AB - BACKGROUND: Objectives of this study were to evaluate oncologic outcomes and to provide guidelines for the management of primary myxoid (MLS) and round cell liposarcoma (RCLS). METHODS: A multicenter, retrospective study of 418 cases of MRCLS primarily managed by Canadian multidisciplinary sarcoma teams. RESULTS: Study included 418 cases (MLS: 311 patients and RCLS: 107; >5% round cell) with a median age of 45 years and a median follow-up of 5.2 years. Median tumor size was 10 cm, and 81% were deep and 90% were in lower limb. The majority of patients underwent surgical resection and radiotherapy, with a small percentage (6%) receiving chemotherapy. The overall 10-year local control rate was 93% with no differences between MLS and RCLS. Radiotherapy was significant in preventing local relapse and reducing tumor diameter (median=18%) and improving microscopic margin status, but did not impact survival. Radiotherapy and the margin status were independent predictors of local recurrence. The 5- and 10-year metastatic free survivals were 84 and 77% respectively for MLS and 69 and 46% for RCLS. The initial site of metastasis was found in multiple locations (34%) and bone involvement was frequent (40%) with predilection for spine (79%). Round cell percent (>5%) and tumor diameter (>10 cm) correlated with increased risk for metastasis and death. CONCLUSIONS: MLS and RCLS showed different metastatic risk but equally good local control. Radiotherapy was effective in preventing local recurrence and should be delivered as neoadjuvant. New staging strategies are to be defined to account for the unusual metastatic pattern. PMID- 22052113 TI - Crossdisciplinary fundamental research--the seed for scientific advance and technological innovation. AB - As it was earlier in the 1980's, so it is now, fundamental science research is under threat as decisions are made on science funding by people who do not do fundamental research, seem congenitally incapable of understanding what it is and furthermore in the face of countless examples seem blind to how important it has been to the technologies that govern our modern life and will be to the future technologies that we desperately need to develop to survive. In this article some general observations are made on how the fascination for what happens in space and stars was the key trigger that gave birth to Science itself and a particular case is outlined which indicates that this same fascination is still the catalyst of some fundamental breakthroughs today. This article also outlines an archetypal example of the way major breakthroughs are often made by the synergy that comes from cross-disciplinary research in a way which is totally surprising. In this case it started from a curiosity about the quantum mechanical description of molecular dynamics and involved pioneering advances in synthetic organic chemistry which led to the suprising discovery that some exotic carbon molecules were abundant in space and stars. These results initiated an experiment using a new technology that represented a major breakthrough in cluster science. The upshot was totally unpredictable, the birth of a whole new field of Chemistry as well as a paradigm shift in major areas of Nanoscience and Nanotechnology. PMID- 22052114 TI - The political economy of health promotion: part 1, national commitments to provision of the prerequisites of health. AB - Canada is a leader in developing health promotion concepts of providing the prerequisites of health through health-promoting public policy. But Canada is clearly a laggard in implementing these concepts. In contrast, France is seen as a nation in which health promotion concepts have failed to gain much traction yet evidence exists that France does far better than Canada in providing these health prerequisites. Such findings suggest that it is the political economy--or form of the welfare state--of a nation rather than its explicit commitments to health promotion concepts--that shape provision of the prerequisites of health. Part 1 of this article examines how health promotion rhetoric specifically concerned with provision of the prerequisites of health differs among nations identified as being either liberal, social democratic, conservative or Latin welfare states. Governing authorities of nations that are liberal or social democratic welfare states are more likely to make explicit rhetorical commitments to provision of the prerequisites of health, the conservative and Latin states less so. Part 2 of this article provides evidence however, that despite their rhetorical commitments to provision of the prerequisites of health, liberal welfare state nations fall well behind not only the social democratic nations, but also the conservative welfare states in implementing public policies that provide the prerequisites of health. The Latin welfare states express little commitment to provision of the prerequisites of health and rather limited public policy activity towards meeting this aim. PMID- 22052115 TI - The political economy of health promotion: part 2, national provision of the prerequisites of health. AB - Governmental authorities of wealthy developed nations differ in their professed commitments and activity related to the provision of the prerequisites of health through public policy action. Part 1 of this article showed how nations identified as social democratic or liberal welfare states were those where such commitments are present. Nations identified as conservative or Latin welfare states were less likely to express such commitments. However, the political economy literature suggests that despite their expressed commitments to provision of the prerequisites of health, liberal welfare states fare rather poorly in implementing these commitments. The opposite is seen for conservative welfare states. Social democratic welfare states show both commitments and public policy consistent with this objective. Part 2 of this article documents the extent to which public policy activity that provides the prerequisites of health through public policy action differs among varying welfare state regimes. Despite extensive rhetoric concerning the prerequisites of health, nations identified as liberal welfare states do a rather poor job of meeting these goals and show evidence of adverse health outcomes. In contrast, social democratic welfare states fare better in providing such prerequisites--consistent with their rhetorical statements--with better health outcomes. Interestingly, conservative- and to a lesser extent Latin--nations fare well in providing the prerequisites of health despite their lack of explicit commitment to such concepts. Findings suggest that health promoters have to concern themselves with the broad strokes of public policymaking whether or not these policy activities are identified as health promotion activities. PMID- 22052116 TI - In search of excellence. PMID- 22052117 TI - Therapeutic hypothermia: treatment for hypoxic-ischemic encephalopathy in the NICU. AB - Baby M was born limp, blue, and without respiratory effort at 38 weeks gestation to a 38-year-old, gravida 5, para 1, woman. Delivery was vaginal after a rapid progression of labor leaving no opportunity for a cesarean section. No other complications were noted during labor but a large surge at delivery, later diagnosed as uterine rupture, initially raised concerns about placental abruption. Apgar scores were 1, 2, and 4 at one, five, and ten minutes, respectively. She was resuscitated in the delivery room, intubated, and transferred in critical condition to the neonatal intensive care unit (NICU) at the birth hospital. Her initial cord pH was 6.7 and was slightly improved at 7.17 on arterial blood gas after resuscitation. Our NICU team was consulted because of her severe neurologic depression. The birth hospital was within walking distance of our tertiary care center and our neurologists went to evaluate her for the hypothermia protocol. Her neurologic exam was notable for dilated and unresponsive pupils, no spontaneous movements, and diminished reflexes and tone, consistent with moderate-to-severe encephalopathy. Seizure activity began at one hour of age and consisted of lip smacking, which was later confirmed by electroencephalogram (EEG). Enrollment criteria were met based on respiratory depression at birth requiring intubation and continued need for ventilation, concern for placental abruption, cord pH less than 7, and encephalopathy on exam and EEG. After stabilizing her airway and achieving central access to treat acidosis and seizures, the team prepared her for transfer to our NICU. At this point, the primary concern became her neurologic status. PMID- 22052118 TI - Neutral head positioning in premature infants for intraventricular hemorrhage prevention: an evidence-based review. AB - With the advancement of neonatal medicine during the past several decades, premature and critically ill infants are living past the neonatal period and surviving. The survival of these infants at smaller birth weights and younger gestational ages puts them at an increased risk for intraventricular hemorrhages (IVHs). Although shifts in cerebral perfusion have been linked to the development of these brain bleeds, many seemingly benign care activities have been linked to changes in cerebral blood flow patterns, possibly contributing to IVHs. The purpose of this article is to evaluate the current evidence to determine if the practice of midline positioning for infants born less than 32 weeks gestation for possible IVH prevention is supported by the literature. Many of the researchers involved in these studies attributed the consequential venule leakage of blood to occlusion of the jugular venous drainage system following a turn in the position of the head. Additionally, the articles that examined the connection between the effects of head tilting on brain hemodynamics attributed changes on the infants' potential inability to autoregulate cerebral blood flow adequately. Both of these findings were linked to the development of IVHs. Based on physiologic data and expert opinion, the authors found support in the literature and recommend implementing a plan of care that includes midline head positioning for premature infants. PMID- 22052119 TI - Congenital central hypoventilation syndrome and the PHOX2B gene mutation. AB - Congenital central hypoventilation syndrome (CCHS) is a rare syndrome of dysfunction of the autonomic nervous system characterized by a decreased response to hypercarbia. It is a disorder in which affected individuals fail to breathe during sleep despite progressive hypercapnia and hypoxia. Infants simply fall asleep and quit breathing. They are found by their parents or caregivers blue and lifeless. CCHS is an autosomal dominant disease. It has been linked with tumors of neural crest origin, segmental aganglionosis of the colon, and diffuse autonomic dysregulation but can occur alone. Discovery of the genetic link between the paired-like homeobox 2B (PHOX2B) genetic mutations and CCHS represents a breakthrough in the diagnosis of CCHS, association of mutated alleles with disease severity, and clues to the pathophysiology responsible for the disorder. Early genetic screening and intervention can provide the families of these infants with hope for achieving a normal life. PMID- 22052120 TI - Neonatal alloimmune thrombocytopenia: a case study. AB - Neonatal alloimmune thrombocytopenia (NAIT) is a life-threatening disorder caused by fetomaternal platelet incompatibility analogous to that seen in rhesus (Rh) disease. In NAIT , maternal immunoglobulin G (IgG) antiplatelet antibodies cross the placenta, resulting in rapid destruction and removal of fetal platelets by the reticuloendothelial system. Studies have shown that NAIT has an incidence of 1 of 1,000 live births, with a mortality rate of 10-15 percent and the risk of long-term morbidities up to 20-60 percent if intracranial hemorrhage (ICH) occurs. This column will discuss the pathophysiology, differential diagnosis, morbidities, and treatment of NAIT and conclude with a relevant case study. PMID- 22052121 TI - Caffeine citrate therapy for apnea of prematurity. PMID- 22052122 TI - Mastering basic computer competencies one byte at a time. PMID- 22052125 TI - Celebrating neonatal nurses who paved the way. AB - As part of the 30th Anniversary of Neonatal Network and the 10th Anniversary of the Academy of Neonatal Nursing, an honor wall was created for the national meeting held in September in Washington, DC. The list below, by no means exhaustive, features some of the neonatal nurses who have made significant contributions to our field. Nurses attending the conference were also invited to honor their own neonatal mentors on a write-in wall of fame. Who is your neonatal hero? PMID- 22052126 TI - Serum MMP-9 is elevated in children with asthma. AB - This study explored the association of matrix metalloproteinase-9 (MMP-9) serum concentration and gene polymorphism with childhood asthma. Serum levels of MMP-9 were determined by sandwich enzyme-linked immunosorbent assay (ELISA) in 65 children with asthma (cases) and 68 healthy children (controls), and the -1562C/T polymorphism in MMP-9 was detected by polymerase chain reaction and restriction fragment-length polymorphism (PCR-RFLP) analysis. The results showed that the mean serum levels of MMP-9 in the children with asthma (136.53 +/- 29.96 ng/ml) were significantly higher than that in the healthy controls (45.08 +/- 12.53 ng/ml; P<0.05). At MMP-9 base position -1562, the frequencies of the genotypes CC, CT and TT in cases were 67.7, 29.2 and 3.1% and in controls were 73.5, 25.0 and 1.5%. The allele frequencies of C and T in cases vs. controls were 82.3 and 17.7% vs. 86.0 and 14.0%, respectively. No statistically significant difference was detected in genotype or allele frequency between these groups. In addition, no significant difference in serum levels of MMP-9 was observed within groups among children with different genotypes (P>0.05). Therefore, whereas serum levels of MMP-9 are associated with the occurrence of childhood asthma, the MMP-9 1562C/T gene polymorphism has no correlation with the pathogenesis of childhood asthma. PMID- 22052127 TI - Imaging in sarcoma. AB - Imaging has contributed to diagnosis and treatment decision making for patients with sarcomas, a highly heterogeneous tumor group. Derived from mesenchymal tissues, sarcomas occur in all parts of the body and in all patient age groups, with a highly variable histologic appearance and behavior. They are commonly separated into soft-tissue-derived and bone-derived groups; however, many exceptions to these classifications are seen clinically. Tumor size, cellular type and differentiation, and presence of necrosis are tumor features that can be used clinically to predict the risk of aggressive behavior. At present for soft tissue sarcomas, the 5-y survival is approximately 60%, with substantially better survival for patients with bone tumors, particularly pediatric patients. Imaging with nuclear medicine techniques plays an important role in diagnosis, treatment planning, and follow-up. Conventional (99m)Tc-methylene diphosphonate bone scans, (201)Tl tumor imaging, and PET techniques have contributed to the care of sarcoma patients. Newer PET techniques with biologically specific imaging agents have also been evaluated to characterize sarcomas and contribute to risk stratification for poor outcome. PMID- 22052128 TI - Complementary roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in medullary thyroid cancer. AB - Serum calcitonin and carcinoembryonic antigen (CEA) are markers of recurrent or persistent disease in medullary thyroid cancer (MTC). However, conventional imaging often fails to localize metastatic disease. Our aim was to compare fluorine-labeled dihydroxyphenylalanine ((18)F-DOPA) and (18)F-FDG PET/CT with multidetector CT (MDCT) and MRI in recurrent or persistent MTC. METHODS: Nineteen MTC patients with increased calcitonin or CEA on follow-up (mean +/- SD, 93 +/- 91 mo; range, 4-300 mo) after primary therapy were prospectively imaged with 4 techniques: (18)F-DOPA PET/CT, (18)F-FDG PET/CT, MDCT, and MRI. Images were analyzed for pathologic lesions, which were surgically removed when possible. The correlation between the detection rate for each method and the calcitonin and CEA concentrations and histopathologic findings was investigated. RESULTS: On the basis of histology and follow-up, one or more imaging methods accurately localized metastatic disease in 12 (63%) of 19 patients. The corresponding figures for (18)F-DOPA PET/CT, (18)F-FDG PET/CT, MDCT, and MRI were 11 (58%) of 19, 10 (53%) of 19, 9 (47%) of 19, and 10 (59%) of 17, respectively. Calcitonin and CEA correlated with (18)F-DOPA PET/CT (P = 0.0007 and P = 0.0263, respectively) and (18)F-FDG PET/CT findings (both P < 0.0001). In patients with an unstable calcitonin doubling time (n = 8), (18)F-DOPA and (18)F-FDG PET/CT were equally sensitive. In contrast, for patients with an unstable CEA doubling time (n = 4), (18)F-FDG PET/CT was more accurate. CONCLUSION: For most MTC patients with occult disease, (18)F-DOPA PET/CT accurately detects metastases. In patients with an unstable calcitonin level, (18)F-DOPA PET/CT and (18)F-FDG PET/CT are complementary. For patients with an unstable CEA doubling time, (18)F FDG PET/CT may be more feasible. MRI is sensitive but has the highest rate of false-positive results. PMID- 22052129 TI - Smartphone app use among medical providers in ACGME training programs. AB - The past decade has witnessed the advent of the smartphone, a device armed with computing power, mobility and downloadable "apps," that has become commonplace within the medical field as both a personal and professional tool. The popularity of medically-related apps suggests that physicians use mobile technology to assist with clinical decision making, yet usage patterns have never been quantified. A digital survey examining smartphone and associated app usage was administered via email to all ACGME training programs. Data regarding respondent specialty, level of training, use of smartphones, use of smartphone apps, desired apps, and commonly used apps were collected and analyzed. Greater than 85% of respondents used a smartphone, of which the iPhone was the most popular (56%). Over half of the respondents reported using apps in their clinical practice; the most commonly used app types were drug guides (79%), medical calculators (18%), coding and billing apps (4%) and pregnancy wheels (4%). The most frequently requested app types were textbook/reference materials (average response: 55%), classification/treatment algorithms (46%) and general medical knowledge (43%). The clinical use of smartphones and apps will likely continue to increase, and we have demonstrated an absence of high-quality and popular apps despite a strong desire among physicians and trainees. This information should be used to guide the development of future healthcare delivery systems; expanded app functionality is almost certain but reliability and ease of use will likely remain major factors in determining the successful integration of apps into clinical practice. PMID- 22052131 TI - Neurology section research strategic plan*. PMID- 22052130 TI - Muscular and gait abnormalities in persons with early onset multiple sclerosis. AB - BACKGROUND AND PURPOSE: Muscular and gait abnormalities are common complaints among persons with multiple sclerosis, even in the early stages of the disease. Our aim was to evaluate peak isometric strength, major lower limb muscle fatigue, and spatiotemporal gait parameters in persons with a first neurological event suggestive of multiple sclerosis, defined as a clinically isolated syndrome (CIS). METHODS: Fifty-two individuals (36 women, 16 men) with CIS, aged 35.2 (SD = 7.2) with an Expanded Disability Status Scale score of 1.7 (SD = 1.3), participated in the study. Peak isometric torque and fatigue index were measured at the knee and ankle bilaterally as well spatiotemporal parameters of gait. Twenty-eight age- and gender-matched healthy subjects served as controls. RESULTS: The CIS group demonstrated increased muscle fatigue, and greater ankle muscle torque asymmetries compared with the control group. The overall fatigue index scores intensified on an average of 40% in the CIS group (27% vs 19% in controls). Participants in the CIS group walked with a larger step length difference, longer step time difference, wider base of support, and prolonged double support period compared with the control group. Positive correlations were identified between double support period and some muscle parameters. DISCUSSION AND CONCLUSION: At this early stage of clinically isolated syndrome, evidence of a reduction in lower limb motor performance can already be identified. The possibility of early identification and potential for developing an intervention program that may alter treatment outcome warrants further exploration. PMID- 22052132 TI - Speed-dependent body weight supported sit-to-stand training in chronic stroke: a case series. AB - BACKGROUND AND PURPOSE: Body weight support (BWS) and speed-dependent training protocols have each been used for poststroke gait training, but neither approach has been tested in the context of sit-to-stand (STS) training. This study evaluated the feasibility and outcomes of speed-dependent BWS STS training for 2 persons with chronic stroke. CASE DESCRIPTIONS: Two individuals 68 and 75 years old, and 2.3 and 8.7 years post-ischemic stroke, respectively, participated. Both exhibited right hemiparesis, required moderate (25%-50%) assistance for STS, and ambulated household distances with assistive devices. INTERVENTION: Participants performed speed-dependent BWS STS training 3 days/week for 45 to 60 minutes until able to perform STS independently. Gait parameters, the Stroke Impact Scale Mobility Domain (SIS-mobility), and the 3-Repetition STS test (3RSTS) were assessed before and after intervention. OUTCOMES: Each participant completed more than 750 STS repetitions over the course of the intervention, achieving independence in 8 to 11 sessions. Aside from muscle soreness, no adverse effects occurred. Participants also exhibited increased gait velocity (0.17-0.24 m/s and 0.25-0.42 m/s), SIS-mobility score (78-88 and 63-66), and decreased 3RSTS time (18-8 seconds and 40-21 seconds). DISCUSSION: Speed-dependent BWS STS training appears to be a feasible and promising method to increase STS independence and speed for persons with chronic stroke. In this small case series, a potential transfer effect to gait parameters was also observed. Future randomized controlled study is warranted to evaluate efficacy and long-term effects. PMID- 22052135 TI - Are health insurance premiums higher for small firms? AB - Large and small firms pay similar health insurance premiums but this similarity is misleading. Small firms are less likely to offer insurance and when they do, provide less generous benefits than large firms. Premium data does not include the experience of small firms that do not offer coverage, perhaps because they faced higher premiums. This synthesis explores the reasons premiums for small firms are higher than large firms. Findings include: Instability causes higher insurance costs for small firms. Small firms have more employee turnover; they drop and add coverage more often; and are more likely to go out of business; this leads to higher administrative costs. Premiums for small firms are more variable because they are more likely to face medical underwriting. Small firms with high average wages are just as likely to offer a health plan as larger firms, but low wage small firms are much less likely to provide coverage. PMID- 22052133 TI - Patterns of gait variability across the lifespan in persons with and without down syndrome. AB - BACKGROUND AND PURPOSE: Greater gait variability has been observed in persons with Down syndrome (DS). An understanding of baseline patterns of variability, how these patterns relate to adaptive control of gait, and whether increasing or decreasing variability is better is necessary for physical therapists to determine whether and when to intervene. Our aim was to describe patterns of gait variability across the lifespan in persons with DS. METHODS: We examined differences in patterns of gait variability in new walkers, preadolescents, and adults with DS and typical development (TD). We collected kinematic data, while participants walked on a treadmill, and analyzed the data using the nonlinear measures of Lyapunov Exponent (LyE) and Approximate Entropy (ApEn). RESULTS: Beyond the greater gait variability demonstrated across the lifespan in persons with DS compared with their peers with TD, we report herein significant differences in nonlinear measures of patterns of variability. Preadolescents demonstrated higher LyE and ApEn values than new walkers and adults, suggesting that they are more adaptive in their use of variability during gait. CONCLUSION: From a clinical perspective, our results suggest that it may be of value to focus interventions on increasing adaptive use of variability during gait in new walkers and adults with DS. Experience with increased variability through practice under variable conditions or with perturbations may improve adaptive use of variability during gait. PMID- 22052136 TI - Distribution of selenium, molybdenum and uranium in sediment cores from the Colorado River delta, Baja California, Mexico. AB - The distribution of selenium, molybdenum and uranium was studied in ~1.5 m sediment cores from the Colorado River delta, at the Colorado (CR) and Hardy (HR) riverbeds. Core HR2 showed highest Se, Mo and U concentrations at its bottom (2.3, 0.95 and 1.8 MUg g(-1)) within a sandy-silt layer deposited prior to dam construction. In CR5 the highest concentrations of these elements (0.9, 1.4 and 1.7 MUg g(-1) respectively) were located at the top of the core within a surface layer enriched in organic carbon. A few samples from HR2 had Se above the probable toxic effect level guidelines. PMID- 22052137 TI - Phytoextraction of endosulfan a remediation technique. AB - Endosulfan is a cyclodiene insecticide used all over the world for the control of various insect pests on variety of food and non crop products. Despite judicious use endosulfan has been detected in atmosphere, soil, water, sediment, surface water rain water and food stuffs, which is of concern. In view of the above the use of mustard and maize plants as potential phytoremediation inputs have been evaluated. The potential of mustard (brassica campestris Linn.) and maize (Zea Maize) to remove a organochlorine pesticide endosulfan was investigated. The disappearance rate constants of endosulfan from soil were 0.03684, 0.23490 and 0.17272 day(-1) for unplanted treatment, planted with mustard and maize, respectively, which implied that plant uptake and phytoextraction with maize and mustard contributed 47.2% and 34.5%, respectively and other degradation processes took up 38.7% and 35.9%, respectively to the removal of the applied endosulfan from soil. The accumulated endosulfan decreased by 55%-91% in soil after growing the crop plants in soil, suggesting that plant uptake and phytoextraction might be the dominant process for endosulfan removal by the plant. This plant might be utilized as an efficient, economical and ecological alternative to accelerate the removal and degradation of agro-industrial wastewater polluted with endosulfan. PMID- 22052138 TI - Preeclampsia/eclampsia: an insight into the dilemma of treatment by the anesthesiologist. AB - A complicated and controversial subject in obstetrics i.e., toxemia of pregnancy is looked upon, both from an anesthesiological and obstetrical point of view. As pre-eclampsia and eclampsia involve immediate treatment and obstetric considerations, the choice between epidural and general anesthesia becomes necessary when cesarean section is contemplated. Apart from the pathophysiology of the vessel spasm as it is induced by preeclampsia, the therapeutic managements of fluid administration, the drugs of choice to treat hypertension as well as the technical aspects of anesthesia are reviewed. PMID- 22052139 TI - Comparison of two regimens of RhG-CSF in neutropenic neonatal septicemia: a randomized clinical trial. AB - Considering the 50% mortality rate of neonatal septicemia associated with neutropenia and increasing resistance to antibiotics, simultaneous antibiotic therapy strategies are becoming more important. However, few studies have been performed to evaluate effectiveness of RhG-CSF in the treatment of neutropenia in neonates. This randomized clinical trial was performed on 40 neutropenic neonates with septicemia who were hospitalized in Vali-e-Asr and Mirza Koochak Khan Hospitals (Tehran, Iran). The neonates were randomly divided into two equal groups RhG-CSF was administered as a subcutaneous single dose of 10 MUg/kg/s.c. to neonates in group A and as 10 MUg/kg/s.c./day once daily for 3 days to neonates in group B. CBC and differential count was checked 6, 24 and 48 hours after the last dose. There was no significant difference in mean birth weight, gender, age, and risk factors between two groups. Neutropenia was improved 48 hours after the last dose, whilst there was no significant statistical difference between two groups (P>0.05). The final outcome including death, duration of hospitalization and duration of antibiotics therapy after RhG-CSF administration did not differ between two groups (P>0.05). The results of this study showed that administration of a single dose of RhG-CSF (10 MUg/kg) was effective in treating neonatal septicemic neutropenia. PMID- 22052140 TI - Does allopurinol prevent post endoscopic retrograde cholangio- pancreatography pancreatitis? A randomized double blind trial. AB - Post endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is a frequent complication either for diagnosis or treatment of pancreatobiliary diseases. A number of pharmacological agents have been tried for prevention or alleviation of the complication. Allopurinol with free radical scavenger property has been considered as an effective prophylactic agent in some clinical trials. Administration of allopurinol in these trials was done in a long period before doing ERCP. Hence allopurinol converts to oxupurinol in the liver rapidly; it seems that clinical judgment about the net effect of allopurinol on prevention of post ERCP pancreatitis is doubtful. In this randomized double blind clinical trial, effect of allopurinol on prevention or alleviation of clinical and laboratory signs of pancreatitis has been evaluated in 74 patients undergoing ERCP. Results showed that there is not any difference between allopurinol and placebo in occurrence and severity of post ERCP pancreatitis (P=0.97). Also there is not any significant difference in amylase rises between 2 groups in 8 and 16 hours after ERCP (P=0.947, 0.287 respectively). Beneficial effects of allopurinol in some of the previous studies may be attributed to its active metabolite (oxypurinol). Further studies recommended about the net effect of allopurinol and oxypurinol in the complication. PMID- 22052141 TI - Povidone-iodine and bleomycin in the management of malignant pleural effusion. AB - Malignant pleural effusion is a common complication in certain malignancies. Pleurodesis is the best option most of the time. The purpose of this study was to compare the choice of belomycin with povidone-iodine, which is not only determined by the efficacy of the agent but also by its cost, accessibility, safety, ease of administration and the number of administrations to achieve a complete response. We performed a randomized clinical trial on 39 patients presenting with symptomatic malignant pleural effusion. Patients were selected and randomly assigned to undergo chemical pleurodesis with either bleomycin or povidone-iodine. Primary characteristics of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs. A complete response was obtained in 79% of belomycin group and 75% of povidone iodine group which was not statistically significant. Patients on belomycin treatment had a significantly lower score for dyspnea in one month follow up. This was significant after controlling for age, pain score and dyspnea score after drainage, using general linear model. Due to similar effect and significant cost advantage between bleomycin and povidone-iodine, we conclude that povidone- iodine is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions. PMID- 22052142 TI - How effective is Swedish massage on blood glucose level in children with diabetes mellitus? AB - This study was conducted to determine the effect of Swedish massage on blood glucose level in children with diabetes mellitus (DM). It was prospective randomized controlled trial study that conducted on 36 children, 6-12 years old with DM, recruited from a hospital in Qom City, Iran. The children were randomly assigned to intervention and control groups. Swedish massage was performed 15 minutes, 3 times a week, for 3 months in intervention group. The blood glucose levels were evaluated immediately after every session of massage in two groups. The mean ages of children in the intervention (n=18) and control (n=18) groups were 9.05 +/- 1.55 and 9.83 +/-2.03 years respectively. There was statistically no significant difference in blood glucose levels before intervention between two groups (P=0.586), but the blood glucose levels were lower significantly in intervention group in comparison with control group after intervention (P<0.0001). Addition of Swedish massage to daily routines; exercise, diet and medication regimens, is an effective intervention to reduce blood glucose level in diabetic children. PMID- 22052143 TI - Results of Milwaukee and Boston braces with or without metal marker around pads in patients with idiopathic scoliosis. AB - Bracing is the non-operative treatment of choice for adolescent idiopathic scoliosis (AIS) and careful application of pads on apical segment of curve is very important for correction. Control of pads' appropriate site in brace is not easy by clinical evaluation. Therefore, we decided to compare results of braces which for better control of pads by radiographs, metal marker inserted around pads with those without metal marker. We evaluated 215 consecutive cases (182 female, 33 male) of AIS with 342 major curves from 1993 to 2003. Mean initial age was, 13.2 +/- 1.8 years (9-16) and mean duration of follow-up was, 16.1 +/- 16.4 months (0-114) that treated by 4 type of brace; 89 with type 1(Milwaukee with metal pads), 87 with type 2 (Milwaukee with simple pads), 17 with type 3 (Boston with metal pads) and 22 with type 4(Boston with simple pads). Cobb angle recorded at 5 stages (initial, best, wean, stop and final follow-up). Mean initial Cobb was 36.2 degrees , at stop stage, 35.2 degrees and reached 38 degrees at final follow-up. Overall, 21.3% improved, 42.2% were the same and 36.5% failed. Failure for braces type 1 to 4 were, 40.5%, 34%, 38% and 24% at final follow-up. A total of 59 patients (27.4%) underwent spinal fusion that for brace type 1 to 4 , was, 33, 21, 2 and 3 patients respectively. From 16 cases with initial Cobb of 50 degrees , at follow-up, 12 were >=50 degrees or had spinal fusion. Correction of lumbar (P=0.008) and main thoracic curves (P=0.002) was better by Boston than Milwaukee, however, In general difference between 4 types of braces was not significant and metal marker had no significant effect on results. Two important predictors of brace failure were, initial curve magnitude and brace type, but using metal marker around pads had no effect in results. It seems that bracing did not alter the natural history of scoliosis in early Risser stages with large magnitude of initial curves. Insertion of metal marker around pads is easy and cheap way that facilitate control of pad sites well, so, we recommend to use. PMID- 22052144 TI - Association of sterile pyuria and coronary artery aneurysm in Kawasaki syndrome. AB - Kawasaki disease (KD) is an inflammatory multiorgan disease of unknown etiology. The most dramatic organ involved is the heart. There were a few studies about cardiac involvement and sterile pyuria. This study guides to determine if sterile pyuria is associated with coronary artery aneurysm (CAA) in KD patients and to consider it as a predicting factor for coronary artery involvement. Forty seven patients with KD were studied by echocardiography in admission and one month later. Urine analysis, complete blood count, erythrocyte sedimentation rate and C reactive protein were measured in admission. Data were analyzed using SPSS-14 software. Patients' age was ranged from 13 month to 7 years old (mean age of 3.43 +/- 1.54 years). Thirty patients (63.8%) were male and 17 patients (36.1%) were female. Cardiac involvement was detected in 32 patients (68%) using echocardiography, of which CAA was reported in 8 cases (17%). Six of CAA (75%) were in association with sterile pyuria, although it was statistically insignificant (P>0.05). Although the majority of patients with CAA had sterile pyuria, this association is not statistically significant, thus it couldn't be considered as a predicting factor for CAA. PMID- 22052145 TI - Thyroid-associated ophthalmopathy in Iranian patients. AB - We determined the frequency of clinical thyroid ophthalmopathy in Iranian patients. This cross-sectional study was performed at the Endocrinology Institute of Tehran University of Medical Sciences. All patients with documented thyroid disorders from September 2003 to July 2005 were recruited. Eye examinations included evaluation of soft tissue changes, measurement of proptosis, lid width, lagophthalmos, evaluation of eye muscle function, and determination of visual acuity. The activity of ophthalmopathy was scored according to the NOSPECS scale. Among 851 visited patients, 303 cases had thyroid eye disease (TED). The nature of the ophthalmopathy breaks down as follows: 53.4% were hypothyroid (9.3% Hashimoto disease), 5.5% euthyroid and 41.1% had Graves' disease. The prevalence of TED in males was 60% which was nearly 2 times the prevalence of TED in females. There was a significant relationship between presentation of TED and active smoking of the patients (P<0.0001) while no significant relationship with passive smoking was obtained (P=0.181). The most common clinical sign of TED in descending order respectively were proptosis with 63.4%, soft tissue involvement (40.9%), extraocular muscle involvement (22.1%), corneal involvement (12.9%) and optic nerve dysfunction (6.3%). Myasthenia gravis occurred in only 2 patients. In the logistic regression, occurrence of TED was influenced by cardiovascular disease (OR=5.346), Graves' disease (OR=47.507), radioiodine therapy (OR=2.590), and anti-thyroid medications (OR=0.650). Thyroid ophtalmopathy (orbitopathy) is a matter of important health concern among patients with thyroid disorder. Since TED occurred with a high prevalence in all thyroid states, a close collaboration between endocrinologists and ophthalmologists along with timely referrals of patients with any eye complaint is deemed necessary. Also smoking was the most important risk factor for developing TED. Therefore, it is advisable to raise awareness and to strongly encourage smokers with thyroid disorders to quit smoking. PMID- 22052146 TI - Low grade endometrial stromal sarcoma of uterine: review of 17 cases. AB - Endometrial stromal sarcomas (ESS) are the second most common uterine sarcomas. Endometrial stromal sarcomas account for 0.25% of all uterine malignancies. Uterine sarcomas most often affect postmenopausal women. The aim of this retrospective study was to review the experience in the treatment and clinical outcome of low grade malignant endometrial stromal sarcoma. Seventeen patients with histologically proven low grade ESS in department of Gynecologic Oncology of the Vali-e-Asr Hospital, Tehran-Iran, between 1999 and 2008 were included in the analysis. Demographics, pathology, treatment, time to recurrence, salvage therapy and survival information was collected. The median age of our patients was 45.35 +/- 6.8 (range 36-61). The median parity of the patients was 5 (range 0-8). Most patients were diagnosed at FIGO stage I. The mean survival for patients with stage I and II was 73.5 +/- 35.09 and 57.6 +/- 5.37 months, respectively, with mortality rate of 5.9% through a median follow-up time of 68.82 +/- 30 months. Of 17 patients, seven cases (35.29%) were disease free at 6 years after hysterectomy. Radiotherapy was administered to four patients (23.53%). Only one patient recurred at 10th month after surgery. Surgeries not preserving ovarian function were helpful to decrease the risk of recurrence compared with those sparing ovarian function. PMID- 22052147 TI - An unusual location of ossified intramuscular lipoma: a case report. AB - Lipoma is the most common soft tissue tumor but the presence of osseous component within the tumor is quite rare. Some studies show that less than 1% of lipomas were ossified. We describe the histological, radiological and diagnostic features of an ossified intramuscular lipoma. To the best of the authors' knowledge, a symptomatic ossified intramuscular lipoma without any cortical erosion and hyperostosis has not been previously reported in the literature. PMID- 22052148 TI - Hemobilia due to rupture of hepatic artery pseudoaneurysm. AB - Although gastrointestinal bleeding is common, hemobilia due to the rupture of hepatic artery pseudoaneurysm is uncommon. We report a case of hemobilia which was successfully treated via angiography. PMID- 22052149 TI - The value of ultrasound in diagnosing vesicoureteral reflux in young children with urinary tract infection. AB - Urinary tract infection is a common pediatric problem and vesicoureteral reflux is its most common complication. Detection of this reflux has classically been achieved by voiding cystouretrography (VCUG). Ultrasonography for evaluation of vesicoureteral reflux is shown to be feasible but is not widely accepted. Our aim was to assess the value of routine sonography in detecting vesicoureteral reflux is young children with urinary tract infection. This study was carried out in 105 patients suffering from urinary tract infection admitted to Shahid Sadughi Hospital in Yazd, Iran. These patients were evaluated by two methods (sonography and VCUG). Overall sensitivity and specificity value of sonography in suggesting vesicoureteral reflux were 63% and 95% respectively. The most accurate results were obtained with high grades reflux (75% and 955). The results reconfirmed that sonography is reliable in the exclusion or verification of high grade reflux and it has a low sensitivity in low grade vesicoureteral reflux. PMID- 22052150 TI - Attitudes toward learning communication skills among medical students of a university in Iran. AB - Communication skills play a paramount role in clinical practice. In every clinical setting, medical doctors need to interview their patients efficiently and be persuasive toward their health issues. This study aimed at assessing the attitudes of medical students toward learning communication skills at Hormozgan University of Medical Sciences in Iran. In this cross-sectional study, the questionnaires were distributed to 210 medical students. Twenty eight students were excluded since they either did not return the questionnaires or filled them out incompletely. So, totally 182 questionnaires were analyzed (response rate=%86.6). Data was collected using communication skills attitude scale (CSAS) which consists of 26 items, 13 indicative of positive attitude and 13 indicative of negative attitude toward learning communication skills. Data were analyzed using SPSS16 software. The mean age of the participants was 21.7 (SD=2.7). Male and female students accounted for 38.5% and 61.5% of the participants respectively. The mean scores for positive attitude was 54.8 (SD=7.3) out of 65, and the mean scores for negative attitude was 35.3 (SD=5.9) out of 65. There were statistically significant differences between male and female students and between basic sciences and pathophysiology students on the one hand and clinical course students on the other as regards their attitudes toward learning communication skills (P<0.05). Although students had strongly positive attitudes toward learning communication skills, curriculum planners should not lose sight of negative attitudes and measures need to be taken to minimize or if possible eliminate them. PMID- 22052151 TI - Tax subsidies for private health insurance - july 2009 update. AB - Tax subsides for employer-sponsored health insurance are the largest subsidy for private health insurance and support key mechanisms of the U.S. insurance system, but they overwhelmingly benefit high-wage employees. When employers purchase or provide insurance for their employees, their contributions to the premium are excluded from income and payroll taxes. This tax exclusion provided more than $100 billion in income and payroll tax subsidies in 2002. High-income workers benefit more from these subsidies than those with lower incomes because of their higher marginal tax rate. Applying the tax exclusion in their respective tax brackets means high-income families (those earning more than $200,000) receive a subsidy worth one-third of the premium, while the lowest income families receive a subsidy worth just 10 percent. Despite these issues, ESI is a successful mechanism in many ways, covering a significant majority of Americans and providing a good pooling mechanism. PMID- 22052152 TI - MicroRNA-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis. AB - Lung cancer is the leading cause of cancer deaths in the world. Brain metastasis (BM) can affect about 25% of non-small cell lung cancer (NSCLC) patients during their lifetime. Efforts to characterize patients that will develop BM have been disappointing. MicroRNAs (miRNAs) play a role in regulating a variety of targets and, consequently, multiple pathways, which make them a powerful tool for early detection of disease, risk assessment and prognosis. In this study, using RT-PCR and further northern blot validation, we confirmed that miR-378 was significantly differentially expressed in the matched NSCLC from 8 patients with BM and 21 without BM. Our study showed evidences that miR-378 is associated with non-small cell lung cancer brain metastasis by promoting cell migration, invasion and tumor angiogenesis. MiR-378 may be a potential biomarker for characterizing non-small cell lung cancer brain metastasis and assisting clinicians in stratifying the high-risk patients on a clinical trial for either prophylactic cranial irradiation or a new intervention that may mitigate BM development, ultimately leading to a new standard of care for NSCLC patients. PMID- 22052153 TI - Aptamer-incorporated hydrogels for visual detection, controlled drug release, and targeted cancer therapy. AB - Hydrogels are water-retainable materials, made from cross-linked polymers, that can be tailored to applications in bioanalysis and biomedicine. As technology advances, an increasing number of molecules have been used as the components of hydrogel systems. However, the shortcomings of these systems have prompted researchers to find new materials that can be incorporated into them. Among all of these emerging materials, aptamers have recently attracted substantial attention because of their unique properties, for example biocompatibility, selective binding, and molecular recognition, all of which make them promising candidates for target-responsive hydrogel engineering. In this work, we will review how aptamers have been incorporated into hydrogel systems to enable colorimetric detection, controlled drug release, and targeted cancer therapy. PMID- 22052154 TI - A novel and rapid method for determination of natamycin in wines based on ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry: validation according to the 2002/657/EC European decision. AB - A novel, simple, and rapid reversed-phase liquid chromatography-tandem mass spectrometric methodology was developed for the analysis of natamycin in wine samples. Natamycin was protonated to form singly charged ions in an electrospray positive ion mode. Data acquisition under MS/MS was achieved by applying multiple reaction monitoring (MRM) of three fragment ion transitions (666.3 -> 648.2, 666.3 -> 503.3, and 666.3 -> 485.2) to provide a high degree of sensitivity and specificity. Chromatographic separation was performed on a rapid resolution column using a mobile phase consisting of an acetonitrile/water mixture with a total run time of 5.0 min. After only filtration as pretreatment, the sample was injected into the chromatographic system. The proposed method was validated in terms of selectivity, trueness, precision, decision limit (CCalpha), and detection capability (CCbeta) according to 2002/657/EC Commission decision. The values for trueness, reported as bias (%), agreed with those established by the aforementioned document. Repeatability (intraday variability) values were 12.37% at a concentration of 1.0 MUg L(-1) and 8.99-4.19% at concentrations between 2.5 and 10 MUg L(-1). The overall within-laboratory (interday variability) reproducibility was 15.47% at a concentration of 1.0 MUg L(-1), which was significantly lower than the indicative value reported in the EU decision. The results indicated that the proposed approach is a sensitive, fast, reproducible, and robust methodology suitable for the analysis of natamycin levels in wine samples. PMID- 22052155 TI - Elemental imaging at the nanoscale: NanoSIMS and complementary techniques for element localisation in plants. AB - The ability to locate and quantify elemental distributions in plants is crucial to understanding plant metabolisms, the mechanisms of uptake and transport of minerals and how plants cope with toxic elements or elemental deficiencies. High resolution secondary ion mass spectrometry (SIMS) is emerging as an important technique for the analysis of biological material at the subcellular scale. This article reviews recent work using the CAMECA NanoSIMS to determine elemental distributions in plants. The NanoSIMS is able to map elemental distributions at high resolution, down to 50 nm, and can detect very low concentrations (milligrams per kilogram) for some elements. It is also capable of mapping almost all elements in the periodic table (from hydrogen to uranium) and can distinguish between stable isotopes, which allows the design of tracer experiments. In this review, particular focus is placed upon studying the same or similar specimens with both the NanoSIMS and a wide range of complementary techniques, showing how the advantages of each technique can be combined to provide a fuller data set to address complex scientific questions. Techniques covered include optical microscopy, synchrotron techniques, including X-ray fluorescence and X-ray absorption spectroscopy, transmission electron microscopy, electron probe microanalysis, particle-induced X-ray emission and inductively coupled plasma mass spectrometry. Some of the challenges associated with sample preparation of plant material for SIMS analysis, the artefacts and limitations of the technique and future trends are also discussed. PMID- 22052156 TI - Independent predictors of breast malignancy in screen-detected microcalcifications: biopsy results in 2545 cases. AB - BACKGROUND: Mammographic microcalcifications are associated with many benign lesions, ductal carcinoma in situ (DCIS) and invasive cancer. Careful assessment criteria are required to minimise benign biopsies while optimising cancer diagnosis. We wished to evaluate the assessment outcomes of microcalcifications biopsied in the setting of population-based breast cancer screening. METHODS: Between January 1992 and December 2007, cases biopsied in which microcalcifications were the only imaging abnormality were included. Patient demographics, imaging features and final histology were subjected to statistical analysis to determine independent predictors of malignancy. RESULTS: In all, 2545 lesions, with a mean diameter of 21.8 mm (s.d. 23.8 mm) and observed in patients with a mean age of 57.7 years (s.d. 8.4 years), were included. Using the grading system adopted by the RANZCR, the grade was 3 in 47.7%; 4 in 28.3% and 5 in 24.0%. After assessment, 1220 lesions (47.9%) were malignant (809 DCIS only, 411 DCIS with invasive cancer) and 1325 (52.1%) were non-malignant, including 122 (4.8%) premalignant lesions (lobular carcinoma in situ, atypical lobular hyperplasia and atypical ductal hyperplasia). Only 30.9% of the DCIS was of low grade.Mammographic extent of microcalcifications >15 mm, imaging grade, their pattern of distribution, presence of a palpable mass and detection after the first screening episode showed significant univariate associations with malignancy. On multivariate modeling imaging grade, mammographic extent of microcalcifications >15 mm, palpable mass and screening episode were retained as independent predictors of malignancy. Radiological grade had the largest effect with lesions of grade 4 and 5 being 2.2 and 3.3 times more likely to be malignant, respectively, than grade 3 lesions. CONCLUSION: The radiological grading scheme used throughout Australia and parts of Europe is validated as a useful system of stratifying microcalcifications into groups with significantly different risks of malignancy. Biopsy assessment of appropriately selected microcalcifications is an effective method of detecting invasive breast cancer and DCIS, particularly of non-low-grade subtypes. PMID- 22052157 TI - A novel frequency analysis method for assessing K(ir)2.1 and Na (v)1.5 currents. AB - Voltage clamping is an important tool for measuring individual currents from an electrically active cell. However, it is difficult to isolate individual currents without pharmacological or voltage inhibition. Herein, we present a technique that involves inserting a noise function into a standard voltage step protocol, which allows one to characterize the unique frequency response of an ion channel at different step potentials. Specifically, we compute the fast Fourier transform for a family of current traces at different step potentials for the inward rectifying potassium channel, K(ir)2.1, and the channel encoding the cardiac fast sodium current, Na(v)1.5. Each individual frequency magnitude, as a function of voltage step, is correlated to the peak current produced by each channel. The correlation coefficient vs. frequency relationship reveals that these two channels are associated with some unique frequencies with high absolute correlation. The individual IV relationship can then be recreated using only the unique frequencies with magnitudes of high absolute correlation. Thus, this study demonstrates that ion channels may exhibit unique frequency responses. PMID- 22052158 TI - Further evaluation of quantum chemical methods for the prediction of non-specific binding of positron emission tomography tracers. AB - The non-specific binding of candidate positron emission tomography (PET) radiotracers causes resulting PET images to have poor contrast and is a key determinant for the success or failure of imaging drugs. Non-specific binding is thought to arise when radiotracers bind to cell membranes and moieties other than their intended target. Our previous preliminary work has proposed the use of the drug-lipid interaction energy descriptor to predict the level of non-specific binding in vivo using a limited set of ten well known PET radiotracers with kinetic modelling data taken from the literature. This work validates and extends the use of the drug-lipid interaction energy descriptor using a new set of twenty two candidate PET radiotracers with non-specific binding data recently collected at the same imaging centre with consistent methodology. As with the previous set of radiotracers, a significant correlation is found between the quantum chemical drug-lipid interaction energy and in vivo non-specific binding experimental values. In an effort to speed up the calculation process, several semi-empirical quantum chemical methods were assessed for their ability to reproduce the ab initio results. However no single semi-empirical method was found to consistently reproduce the level of correlation achieved with ab initio quantum chemical methods. PMID- 22052159 TI - BKCa and KV channels limit conducted vasomotor responses in rat mesenteric terminal arterioles. AB - Intracellular Ca(2+) signals underlying conducted vasoconstriction to local application of a brief depolarizing KCl stimulus was investigated in rat mesenteric terminal arterioles (<40 MUm). Using a computer model of an arteriole segment comprised of coupled endothelial cells (EC) and vascular smooth muscle cells (VSMC) simulations of both membrane potential and intracellular [Ca(2+)] were performed. The "characteristic" length constant, lambda, was approximated using a modified cable equation in both experiments and simulations. We hypothesized that K(+) conductance in the arteriolar wall limit the electrotonic spread of a local depolarization along arterioles by current dissipation across the VSMC plasma membrane. Thus, we anticipated an increased lambda by inhibition of voltage-activated K(+) channels. Application of the BK(Ca) channel blocker iberiotoxin (100 nM) onto mesenteric arterioles in vitro and inhibition of BK(Ca) channel current in silico increased lambda by 34% and 32%, respectively. Similarly, inhibition of K(V) channels in vitro (4-aminopyridine, 1 mM) or in silico increased lambda by 41% and 21%, respectively. Immunofluorescence microscopy demonstrated expression of BK(Ca), Kv1.5, Kv2.1, but not Kv1.2, in VSMCs of rat mesenteric terminal arterioles. Our results demonstrate that inhibition of voltage-activated K(+) channels enhance vascular-conducted responses to local depolarization in terminal arterioles by increasing the membrane resistance of VSMCs. These data contribute to our understanding of how differential expression patterns of voltage-activated K(+) channels may influence conducted vasoconstriction in small arteriolar networks. This finding is potentially relevant to understanding the compromised microcirculatory blood flow in systemic vascular diseases such as diabetes mellitus and hypertension. PMID- 22052160 TI - Genetics and language: a neurobiological perspective on the missing link (-ing hypotheses). AB - The paper argues that both evolutionary and genetic approaches to studying the biological foundations of speech and language could benefit from fractionating the problem at a finer grain, aiming not to map genetics to "language"-or even subdomains of language such as "phonology" or "syntax"-but rather to link genetic results to component formal operations that underlie processing the comprehension and production of linguistic representations. Neuroanatomic and neurophysiological research suggests that language processing is broken down in space (distributed functional anatomy along concurrent pathways) and time (concurrent processing on multiple time scales). These parallel neuronal pathways and their local circuits form the infrastructure of speech and language and are the actual targets of evolution/genetics. Therefore, investigating the mapping from gene to brain circuit to linguistic phenotype at the level of generic computational operations (subroutines actually executable in these circuits) stands to provide a new perspective on the biological foundations in the healthy and challenged brain. PMID- 22052161 TI - Effects of an eHealth literacy intervention for older adults. AB - BACKGROUND: Older adults generally have low health and computer literacies, making it challenging for them to function well in the eHealth era where technology is increasingly being used in health care. Little is known about effective interventions and strategies for improving the eHealth literacy of the older population. OBJECTIVE: The objective of this study was to examine the effects of a theory-driven eHealth literacy intervention for older adults. METHODS: The experimental design was a 2 * 2 mixed factorial design with learning method (collaborative; individualistic) as the between-participants variable and time of measurement (pre; post) as the within-participants variable. A total of 146 older adults aged 56-91 (mean 69.99, SD 8.12) participated in this study during February to May 2011. The intervention involved 2 weeks of learning about using the National Institutes of Health's SeniorHealth.gov website to access reliable health information. The intervention took place at public libraries. Participants were randomly assigned to either experimental condition (collaborative: n = 72; individualistic: n = 74). RESULTS: Overall, participants' knowledge, skills, and eHealth literacy efficacy all improved significantly from pre to post intervention (P < .001 in all cases; effect sizes were >0.8 with statistical power of 1.00 even at the .01 level in all cases). When controlling for baseline differences, no significant main effect of the learning method was found on computer/Web knowledge, skills, or eHealth literacy efficacy. Thus, collaborative learning did not differ from individualistic learning in affecting the learning outcomes. No significant interaction effect of learning method and time of measurement was found. Group composition based on gender, familiarity with peers, or prior computer experience had no significant main or interaction effect on the learning outcomes. Regardless of the specific learning method used, participants had overwhelmingly positive attitudes toward the intervention and reported positive changes in participation in their own health care as a result of the intervention. CONCLUSIONS: The findings provide strong evidence that the eHealth literacy intervention tested in this study, regardless of the specific learning method used, significantly improved knowledge, skills, and eHealth literacy efficacy from pre to post intervention, was positively perceived by participants, and led to positive changes in their own health care. Collaborative learning did not differ from individualistic learning in affecting the learning outcomes, suggesting the previously widely reported advantages of collaborative over individualistic learning may not be easily applied to the older population in informal settings, though several confounding factors might have contributed to this finding (ie, the largely inexperienced computer user composition of the study sample, potential instructor effect, and ceiling effect). Further research is necessary before a more firm conclusion can be drawn. These findings contribute to the literatures on adult learning, social interdependence theory, and health literacy. PMID- 22052162 TI - Elevated p-CREB-2 (ser 245) expression is potentially associated with carcinogenesis and development of breast carcinoma. AB - CREB-2, also known as ATF-4, belongs to the CREB proteins, a family of transcription factors phosphorylated at serine residues by protein kinase A (PKA). This family is known to stimulate the transcription of genes containing CRE elements. Recently, some studies have demonstrated elevated CREB-2 expression in certain tumor types, including breast carcinoma, compared to their corresponding non-tumor tissues. However, the expression and clinical significance in malignant tumors, including breast carcinoma, of p-CREB-2 (ser 245), a phosphorylated form of the CREB-2 protein at serine 245 site, which is believed to be an active type of this protein, have not been clearly documented. In the present study, we investigated the expression of p-CREB-2 (ser 245) in a group of tumor and non-tumor breast tissues, including normal breast epithelia, hyperplasia, dysplasia, carcinoma in situ and infiltrating carcinoma of the breast using tissue microarray and immunohistochemistry (IHC). p-CREB-2 (ser 245) immunostaining was detected in the nucleus and cytoplasm of these tissues. Compared to normal breast epithelia and breast hyperplasia (total positive rate 13.3%), there was increased expression of p-CREB-2 (ser 245) in dysplasia, carcinoma in situ (total positive rate 35.7%) and infiltrating carcinoma of the breast (total positive rate 60.0%) (p<0.05). The highest expression of p-CREB-2 (ser 245) was found in infiltrating breast carcinoma (total positive rate 60%) compared to normal breast epithelia and all types of non-infiltrating lesions (total positive rate 27.6%) (p<0.05). In addition, increased expression of p-CREB 2 (ser 245) was found to be associated with lymph node metastasis in infiltrating breast carcinoma (p<0.05). Immunofluorescent staining confirmed stronger staining of p-CREB-2 (ser 245) in breast cancer MCF 7 and MDA-MB-231 cells compared with normal breast epithelial MCF 10A cells. Western blotting revealed elevated expression levels of p-CREB-2 (ser 245) in 17 cases of breast carcinoma compared with corresponding normal breast tissues (p<0.05). These results indicate that elevated expression of p-CREB-2 (ser 245) may potentially contribute to carcinogenesis and cancer development of breast carcinoma. PMID- 22052163 TI - Multiple persistent ganglioneuromas likely arising from the spontaneous maturation of metastatic neuroblastoma. AB - A 10-year-old girl with multiple persistent ganglioneuromas originating from the spontaneous maturation of a metastatic neuroblastoma is described. Multiple biopsies confirm progressive maturation and urine catecholamines, which were initially elevated, have normalized over time. The management and risk of malignant transformation of ganglioneuromas is discussed. PMID- 22052164 TI - An unusual case of congenital primitive neuroectodermal tumor with ocular metastasis. AB - Primitive neuroectodermal tumor (PNET) is most common in the second decade of life. Congenital PNET is very rare. Ocular metastasis of PNET is likewise exceedingly rare; with only 5 previously published cases. We report an unusual congenital PNET of the face, which metastasized to subcutis, eyes, and brain. The primary tumor responded to chemotherapy (vincristine/doxorubicin/cyclophosphamide) with metachronous progression of ocular lesions. A therapeutic trial of intraocular bevacizumab showed no efficacy on intraocular lesions. Eventually the patient developed cerebral metastasis, and second line therapy with topotecan/cyclophosphamide was initiated. The tumor progressed and the patient died after acute herniation. PMID- 22052165 TI - Extrarenal malignant rhabdoid tumor in childhood application of 18F-FDG PET/CT. AB - Extrarenal malignant rhabdoid tumor (MRT) is a rare malignancy in childhood and has a poor prognosis. Accurate histopathologic diagnosis and staging of the malignancy has major implications for patient management. The application of F fluoro-deoxy-glucose positron emission tomography/computed tomography (F-FDG PET/CT) in pediatric malignancy has been well described and is having a significant clinical impact in many common pediatric cancers, in particular lymphoma, brain tumors, bone and soft tissue sarcomas. The use of PET/CT using F FDG in rare tumors such as MRT is unclear. Two cases of MRT in childhood are described. One patient, a 12-year-old female, was shown to have extensive metastatic disease on PET/CT, showed poor response to chemotherapy and progression of disease detected on PET/CT. Her management was changed to palliative care. The second child, a 20-month-old female, presented with a parapharyngeal mass. The initial magnetic resonance imaging showed the mass and possible metastatic ipsilateral cervical lymph nodes. The initial staging PET/CT confirmed avid metabolic activity in the tumor and regional node involvement but no distant metastases. She showed an initial good but incomplete response on PET/CT and magnetic resonance imaging to chemotherapy and her treatment program was changed. The patient relapsed with recurrent pharyngeal tumor and her management was changed to palliative care. MRT accumulate F-FDG avidly. PET/CT was helpful in the initial staging, assessing response to treatment, and in clinical decisions at various stages of management for both patients. PMID- 22052166 TI - MLL duplication in a pediatric patient with B-cell lymphoblastic lymphoma. AB - Lymphoblastic lymphoma is the second most common type of non-Hodgkin lymphoma seen in children. Approximately, 90% of lymphoblastic lymphomas arise from T cells, with the remaining 10% being B-cell-lineage derived. Although T-cell lymphoblastic lymphoma most frequently occurs in the anterior mediastinum (thymus), B-cell lymphoblastic lymphoma (B-LBL) predominates in extranodal sites such as skin and bone. Here, we describe a pediatric B-LBL patient who presented with extensive abdominal involvement and whose lymphoma cells displayed segmental duplication of the mixed lineage leukemia (MLL) gene. MLL duplication/amplification has been described primarily in acute myeloid leukemia and myelodysplastic syndrome with no published reports of discrete MLL duplication/amplification events in B-LBL. The MLL gene duplication noted in this case may represent a novel mechanism for tumorigenesis in B-LBL. PMID- 22052167 TI - Promoter of TFPI-2 is hypermethylated in Chinese pediatric acute myeloid leukemia. AB - Human tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. In this study, we investigated whether TFPI-2 was inactivated epigenetically in pediatric acute myeloid leukemia (AML). Methylation status was investigated by methylation specific polymerase chain reaction and bisulfate genomic sequencing. TFPI-2 was aberrantly methylated in 50% (3/6) of AML cell lines. Aberrant methylation of TFPI-2 promoter was detected in 71.6% (48/67) of the Chinese pediatric AML patients. TFPI-2 transcript was significantly lower in AML group compared with controls (3.44 vs. 32.8, P<0.001). Patients with methylated TFPI-2 gene had significantly lower TFPI-2 transcript than those patients without methylated TFPI 2 (P=0.04). Promoter hypermethylation of TFPI-2 is frequent and specific event in pediatric AML. PMID- 22052168 TI - Esophageal carcinoma in children and adolescents. AB - BACKGROUND: Esophageal cancer is rare in children and is limited to isolated case reports. We describe 2 cases of esophageal carcinoma (1 case each of squamous cell carcinoma and adenocarcinoma) and present literature review of esophageal carcinoma in childhood. OBSERVATIONS: Both of our patients had common symptoms of progressive dysphagia and significant weight loss at presentation. We were unable to identify any specific predisposing factors for either adenocarcinoma (caustic ingestion, reflux disease, Barrett esophagus) or squamous cell carcinoma (caustic ingestion, inherited bone marrow failure syndromes). Both patients responded poorly to chemotherapy and died of progressive disease. CONCLUSIONS: On account of the rarity of esophageal carcinoma in this age group, there are no management guidelines for the pediatric oncologist. There is a strong need for collaborative efforts between adult and pediatric oncologists to establish cooperative diagnostic and therapeutic protocols for successful management of rare pediatric tumors like esophageal carcinoma. PMID- 22052169 TI - In vitro determination of apoptotic effect of heparin on lymphoblasts by using flow cytometric DNA analysis and measurements of caspase-9 activation and cytochrome C level. AB - Heparin induces apoptosis on peripheral neutrophils, mononuclear cells of the healthy controls, and on lymphoblasts of the patients with acute lymphoblastic leukemia, in vitro. We studied the caspase-9 activity and cytochrome C level as the indicators of the apoptotic effect of heparin on lymphoblasts by the intrinsic pathway of apoptosis. Twenty samples of the patients with acute lymphoblastic leukemia were included in the study. Cytochrome C level and caspase 9 activity were concomitantly determined with the percentage of apoptotic lymphoblasts when incubated in 0, 10, and 20 U/mL heparin concentrations at 0, 1, and 2 hours. The percentages of apoptosis of lymphoblasts at the first hour were higher than those at 0 and 2 hours in 10 and 20 U/mL heparin concentrations, separately (P<0.05). The mean percentage of apoptosis of lymphoblasts in 20 U/mL heparin levels was significantly higher than those in 0 and 10 U/mL heparin levels at 1 and 2 hours (P<0.05). The highest apoptotic effect of heparin on lymphoblasts was determined at the first hour in 20 U/mL heparin concentration. The mean caspase-9 activitity at the first hour was significantly higher than the values at 0 and 2 hours in 10 and 20 U/mL heparin levels, separately (P<0.05). The mean caspase-9 activity in 20 U/mL heparin concentration was significantly higher than values in 0 and 10 U/mL heparin concentrations at 1 and 2 hours (P<0.05). The highest caspase-9 activity was determined in 20 U/mL heparin levels at the first hour. The mean cytochrome C level at the first hour was significantly higher than those at 0 and 2 hours in 10 and 20 U/mL heparin concentrations, separately (P<0.05). The highest cytochrome C level was determined in 20 U/mL heparin concentration at the first hour. We claimed that heparin induces the apoptosis of lymphoblasts by the activation of the intrinsic pathway. PMID- 22052170 TI - Life-threatening and fatal infections in children with acute myeloid leukemia: a report from the Children's Oncology Group. AB - To determine among children with acute myeloid leukemia, whether the proportions of life-threatening or fatal infections differed according to the intensity of induction or type of intensification treatment. Participants were children enrolled to the Children's Cancer Group (CCG) 2891 with de novo acute myeloid leukemia. In phase 1 (induction) patients were randomized to 4 cycles of chemotherapy either administered as intensive or standard timing. In phase 2 (intensification), those achieving remission were allocated to allogeneic stem cell transplantation (SCT) if a suitable family donor was available while the remainder were randomized to autologous SCT or chemotherapy. Each infection was classified prospectively as nonlife-threatening, life-threatening, or fatal. The proportion of all infections that were considered life-threatening or fatal was higher with intensive timing compared with standard timing induction (60.3% vs. 37.3%, P<0.0001). Infections caused by Gram-positive and Gram-negative bacteria and fungi were significantly more likely to be severe during intensive compared with standard timing induction. Most molds were life-threatening or fatal. Chemotherapy intensification was not associated with less severe infections compared with SCT. Intensive timing was associated with more severe infections compared with standard timing induction. Prophylactic strategies are likely more important with intensive induction regimens. PMID- 22052171 TI - Greater maternal weight gain during pregnancy predicts a large but lean fetal phenotype: a prospective cohort study. AB - The objective of this study is to describe the fetal phenotype in utero and its associations with maternal pre-pregnancy weight and gestational weight gain. This prospective longitudinal cohort included 179 Australian women with singleton pregnancies. Serial ultrasound measurements were performed at 19, 25, 30 and 36 (+/-1) weeks gestation and maternal anthropometry were collected concurrently. The ultrasound scans included the standard fetal biometry of head circumference, biparietal diameter, abdominal circumference, and femur length, and body composition at the abdomen and mid-thigh, including fat and lean mass cross sectional areas. Maternal gestational weight gain was compared to current clinical guidelines. The participants had an average of 3.7 +/- 0.8 scans and birth data were available for 165 neonates. Fifty four per cent of the cohort gained weight in excess of current recommendations, according to pre-pregnancy body mass index (BMI). Maternal gestational weight positively predicted fetal abdominal circumference (P 0.029) and lean abdominal mass area (P 0.046) in linear mixed model regression analysis, adjusted for known and potential confounders. At any pre-pregnancy BMI gaining weight above the current recommendations resulted in a larger fetus according to standard biometry, because of significantly larger lean muscle mass at the abdomen (P 0.024) and not due to an increase in fat mass (P 0.463). We have demonstrated the importance of maternal weight gain, independent of pre-pregnancy BMI, to support the growth of a large but lean fetus. Prenatal counselling should focus on achieving a healthy BMI prior to conception so that gestational weight gain restrictions can be minimised. PMID- 22052172 TI - [Spanish multi-centre observational study of the first attacks suggestive of multiple sclerosis: the PREM cohort]. AB - INTRODUCTION: Recent studies have shown the need to optimise the management of patients after a first attack suggestive of multiple sclerosis (MS). Our aim is to determine whether the results from follow-ups in these studies are reproducible within a Spanish multi-centre context. PATIENTS AND METHODS: The PREM study (observational prospective Spanish multi-centre study at 24 months) included patients in the first three months following a first event suggestive of MS with at least two typical lesions in a magnetic resonance scan. The Expanded Disability Status Scale (EDSS) was obtained and the presence of attacks was evaluated basally and at 3, 6, 9, 12, 18 and 24 months; a magnetic resonance scan was performed basally and at 6 and 24 months so as to be able to calculate the brain volume and the volumes of the lesions (T1, T2 and T1 after administering gadolinium). McDonald and Poser criteria were evaluated during the follow-up. A subgroup of patients was followed up for a total period of four years. RESULTS: Altogether 110 patients (67% females) with a mean age of 30.2 years were included in the study; 22 patients dropped out of the study before it finished. Poser criteria were met by 19% and 45% of patients at 6 months and 24 months, respectively; 63% and 71% satisfied McDonald criteria. The EDSS decreased significantly (-0.94; p < 0.001) and development of atrophy was observed (-1.2%; p < 0.001) at 24 months. CONCLUSIONS: Results of the follow-up of patients with first attacks suggestive of MS within a Spanish multi-centre context are wholly comparable with those from international clinical trials performed in these patients. PMID- 22052173 TI - [Aspirin versus anticoagulation in young patients with cerebral infarction secondary to primary antiphospholipid syndrome]. AB - INTRODUCTION: The primary antiphospholipid syndrome (PAS) is an independent risk factor for cerebral infarction. AIM. To evaluate the risk of recurrence, to compare different treatments and determine the risk factors associated with recurrence and hemorrhagic complications in patients with cerebral infarction and PAS. PATIENTS AND METHODS: Prospectively collected data from 92 patients under 45 years (71% female, mean age 33.8 +/- 8.9 years) with confirmed diagnoses of cerebral infarction and PAS, treated with anticoagulants (n = 54) or aspirin (n = 38) were retrospectively analyzed. Clinical follow-up was obtained by neurological examination every 6 to 12 months. Outcome measures were: recurrence of CI, symptomatic intracerebral hemorrhage, and minor bleeding. RESULTS: During a median follow-up of 54 months (range: 12-240 months), there were 8 (9%) recurrent cerebral infarctions, with no difference between treatment with aspirin (n = 0) or anticoagulants (n = 8). The annual rate of recurrence was 0,014 person years of follow-up. The history of previous thrombosis and spontaneous abortions were more frequent in patients with recurrence. Aspirin-treated patients more frequently came from rural areas. Four anticoagulated patients developed bleeding complications, two minor bleeding and two subdural hematomas. 76% of the cases evolved with good outcome (modified Rankin scale: 0-2). CONCLUSION: With the limitations of a nonrandomized study, our data suggest that the risk of recurrent arterial cerebral infarction in young patients with cerebral infarction secondary to PAS is low, probably non-uniform and independent of the type of antithrombotic. PMID- 22052174 TI - [Evolution of the literature on clinical neurology in Spain, France, Italy and Germany over the period 2000-2009]. AB - AIM: This study analyzes the productivity and visibility of Spanish publications in the area of clinical neurology in the period 2000-2009 and compared with those for Italy, France and Germany. MATERIALS AND METHODS: We used the database Web of Science. The analysis (annual and in five-year) was restricted to the citable documents (original articles, reviews and proceedings papers). Bibliometric indicators used were the number of publications, citations received by publications and Hirsch's h-index. We also assessed the slope of the annual growth rate (b), the number of publications by language and the international collaboration. RESULTS: In the period 2000-2009 there were 46,114 publications in neurology clinic of which 6,998 were Spanish publications (h = 75), 11,629 in Italy (h = 101), French 9,745 (h = 102) and 20,143 in Germany (h = 124). The rate of increase in the total number of publications in Spain (b = 15) was lower than that observed in Italy (b = 65), Germany (b = 61) or France (b = 34). In the case of publications in English, the growth rate was higher for Spain (b = 37) than for France (b = 36) but lower than for Germany (b = 54) and Italy (b = 65). CONCLUSIONS: Although the total number of publications and the observed increase are lower in Spain compared to Italy, France or Germany, the Spanish publications in Clinical Neurology shows good trend indicators with regard to publications in English and international collaboration. This improvement was associated with greater visibility as showed by the five-year analysis of citations received by Spanish publications. PMID- 22052175 TI - [Hospital processes and costs in neurology. A study of a referral hospital]. AB - INTRODUCTION: The steady growth of spending on healthcare and the limited availability of resources make it necessary to include cost analysis among the tools used for hospital management. AIMS. To obtain the hospitalisation operating statement of a neurology service and to analyse the differences with regard to costs per process. PATIENTS AND METHODS: The study involved an analysis of costs per process in the neurology service of a referral hospital in the Valencian Community (400,000 inhabitants). The data used were those concerning health care activity in 2008 according to the information registered by the Economic Information System of the Valencian Regional Ministry of Health; ABC and top-down methods were applied to calculate the cost per process. The results thus obtained were compared with the fees established for hospital production in the Valencian Regional Government's Law on Fees. RESULTS: For a production of 1092 hospital discharges, with a case-mix index of 0.96 and a mean length of stay of 9.2 days with a case mix of 1.91, hospitalisation costs came to 4,411,643.45 euros, with a mean cost per process of 2,111.46 euros. Taking into account the fees that were applied, the difference between income and expenditure was -12,770.39 euros. The diagnosis-related groups with the greatest difference were numbers 14 ( 246,392.49 euros), 533 (-90,292.49 euros) and 15 (-55,139.66 euros). CONCLUSIONS: The hospitalisation profit and loss account obtained is negative due to the fact that the mean length of stay in the service is longer than expected, above all in diagnosis-related groups 14, 533 and 15, which are the most inefficient. PMID- 22052176 TI - Neurological tests for functional outcome assessment in rodent models of ischaemic stroke. AB - A critical aspect in all models is the assessment of the final outcome of the modelling procedure. In the case of a focal ischaemic brain injury, apart from the determination of the size of the lesion, another valuable tool is the evaluation of the final functional deficit. Indeed, ischaemic damage leads to the appearance of different degrees of sensoriomotor and cognitive impairments, which may yield useful information on location and size of the lesion and on the efficacy of neuroprotective treatments after the acute injury. In addition, the magnitude of these impairments may also be useful to predict final outcome and to evaluate neuro-restorative therapies in a long-term scenario. To this aim, a wide range of tests has been developed which allow the quantification of all these neurological symptoms. This review intends to compile the most useful behavioural tests designed to assess neurological symptoms in studies of focal experimental cerebral ischemia in rodents induced by middle cerebral artery occlusion, the most commonly used model of ischaemic stroke. PMID- 22052178 TI - [Complete ophthalmoplegia secondary to a bilateral paramedian thalamic infarct]. PMID- 22052179 TI - [Lethal catatonia as a manifestation of malignant bipolar disease]. PMID- 22052180 TI - [The need for scientific information in neuropaediatrics]. PMID- 22052181 TI - Tax subsidies for private health insurance. AB - The exclusion from income and payroll taxes for employer-paid health insurance premiums amounted to more than $240 billion in 2010. As policy-makers search for ways to pay for health care reform and contain health care costs, this exclusion is coming under scrutiny, despite the fact that employee-sponsored insurance (ESI) is an integral part of the health insurance system. This update of a 2003 synthesis looks at the tax subsidy for private health insurance. Key findings include: The current tax subsidy benefits higher-income workers the most. The tax exclusion is worth more to those in higher tax brackets, higher-income workers are three times more likely to work for firms who offer ESI than lower-income workers, and they are more likely to purchase ESI when offered because they can afford it. Families earning $10,000 to $20,000 annually spend more than 25 percent of their income on health insurance but the value of their tax subsidy is only $1,500. By contrast, earners over $200,000 spend less than 5 percent on health insurance but their benefit is worth $4,500. Workers who cannot afford ESI or are ineligible, including the self-employed and many part-time workers, do not receive this subsidy when they purchase private, non-group coverage. PMID- 22052182 TI - Cost savings and cost-effectiveness of clinical preventive care. AB - It is well established that preventive care reduces the prevalence of disease and helps people live longer, healthier lives. Analysis of the cost-effectiveness of preventive care can guide policy-makers to allocate scarce resources. This synthesis reviews the evidence on the cost-effectiveness of clinical preventive care. Key findings include: although many preventive services are a good value (defined as costing less than $50,000 to $100,000 per Quality Adjusted Life Year), only a few, such as childhood immunizations and counseling adults on the use of low-dose aspirin are widely regarded as cost-saving. Costs to reduce risk factors, screening costs, and the cost of treatment when disease is found can offset any savings from preventive care. Prevention can reduce the incidence of disease, but savings may be partially offset by health care costs associated with increased longevity. Whether these additional competing risk costs outweigh the savings from avoiding the targeted disease depends on how healthy people are during the added life years. Given that so few preventive services save money and that these services are already in wide use, it is unlikely that prevention can reduce health care spending. The authors question whether the emphasis on savings is appropriate and suggest it is better to focus on high value preventive care, taking into account increased longevity and quality of life. PMID- 22052183 TI - Metastasis of occult prostatic carcinoma to the sphenoid sinus: report of a rare case and a review of the literature. AB - We present a case (55-year-old) with a metastasis to the sphenoid sinus from an occult prostatic adenocarcinoma as the first evidence of disease. The patient's symptoms were progressive left-sided headache of a few months duration and a 2 week history of blurred vision with diplopia. Clinical examination revealed a left cranial nerve III palsy and ptosis. A computed tomography scan showed a 2 cm large, well delineated soft tissue lesion involving the left sphenoid sinus and extending to the left cavernous sinus with sclerosis of the adjacent sphenoid bone. Histological and immunohistochemical examinations revealed a poorly differentiated adenocarcinoma that was positive for prostate specific antigen (PSA) and broad-spectrum cytokeratins (Cam 5.2). Subsequent urological examination confirmed a locally advanced prostatic carcinoma with significantly increased serum-PSA (4,561 MUg/l) and bone scintigraphy showed widespread metastasis. PMID- 22052184 TI - In situ hybridization signal patterns in recurrent laryngeal squamous papillomas indicate that HPV integration occurs at an early stage. AB - Laryngeal papillomas are benign tumors that frequently recur and can compromise airways. We investigated HPV genotype, physical status, and protein expression in juveniles versus adults. Thirty-five laryngeal papilloma specimens were obtained from ten juveniles (1-16 years) and eleven adults (24-67 years). In cases of recurrent papillomatosis (7 juveniles, 7 adults), the first and last papillomas were assayed. HPV type was determined by GP5+/6+ PCR and dot blot hybridization. In situ hybridization (ISH) was performed on 34 specimens; the data were recorded in terms of diffuse (episomal HPV) and punctate (integrated HPV) signal patterns. Immunohistochemistry for the HPV L1 capsid protein, a marker of HPV productive status, was performed on 32 samples. All samples tested HPV positive: HPV 11 in 2/10 (20.0%) juveniles and 5/11 (45.5%) adults; HPV 6 in 7/10 (70%) juveniles and 5/11 (45.5%) adults; and HPV 6/11 double infection was noted in one juvenile and one adult. ISH signals (punctate +/- diffuse) were detected among 7/10 (70.0%) juveniles and 7/11 (63.6%) adults. L1 staining was detected in 1/9 (11.1%) juveniles and 6/10 (60.0%) adults (P = 0.06). These data support the idea that integration of low-risk HPV types into the cell genome is an early and common event in the etiology of juvenile and adult recurrent laryngeal papillomas. Productive HPV infections may be more common in adults; accordingly, constant laryngeal re-infection by HPV shed from a productive lesion may contribute to adult recurrent lesions, whereas the mechanism of papilloma recurrence in juveniles may be more attributable to HPV integration. PMID- 22052185 TI - Time to generate ventilator-induced lung injury among mammals with healthy lungs: a unifying hypothesis. AB - PURPOSE: To investigate ventilator-induced lung injury (VILI), several experimental models were designed including different mammalian species and ventilator settings, leading to a large variability in the observed time-course and injury severity. We hypothesized that the time-course of VILI may be fully explained from a single perspective when considering the insult actually applied, i.e. lung stress and strain. METHODS: Studies in which healthy animals were aggressively ventilated until preterminal VILI were selected via a Medline search. Data on morphometry, ventilator settings, respiratory function and duration of ventilation were derived. For each animal group, lung stress (transpulmonary pressure) and strain (end-inspiratory lung inflation/lung resting volume ratio) were estimated. RESULTS: From the Medline search 20 studies including five mammalian species (sheep, pigs, rabbits, rats, mice) were selected. Time to achieve preterminal VILI varied widely (18-2,784 min), did not correlate with either tidal volume (expressed in relation to body weight) or airway pressure applied, but was weakly associated with lung stress (r (2) = 0.25, p = 0.008). In contrast, the duration of mechanical ventilation was closely correlated with both lung strain (r (2) = 0.85, p < 0.0001) and lung strain weighted for the actual time of application during each breath (r (2) = 0.83, p < 0.0001), according to exponential decay functions. When it was normalized for the lung strain applied, larger species showed a greater resistance to VILI than smaller species (medians, 25th-75th percentiles: 690, 460-2,001 min vs. 16, 4-59 min, respectively; p < 0.001). CONCLUSION: Lung strain may play a critical role as a unifying rule describing the development of VILI among mammals with healthy lungs. PMID- 22052186 TI - Intensive care medicine: finding its way in the "European labyrinth". AB - INTRODUCTION: The European Union (EU) has created recent directives to facilitate the free movement of medical specialists in its member states. METHODS: Analysis of two recent surveys performed in European countries. RESULTS: Intensive Care Medicine training and accreditation have changed quickly over time. There is no harmonisation among European countries. Young specialists might face several difficulties in the future. DISCUSSION: Nations providing a national examination for intensive care medicine and a national register for specialists in intensive care medicine facilitate the free movement of specialists, regardless of European regulations and directives. CONCLUSION: Intensive care medicine is currently not a mother speciality. A long process needs to occur before complete harmonization of training and accreditation and free movement of specialists in Europe will happen. PMID- 22052187 TI - Modeling the time-course of ventilator-induced lung injury: what can we learn from interspecies discrepancies? PMID- 22052188 TI - Text-speak processing and the sustained attention to response task. AB - We examined performance in a sustained attention to response task (SART) (Experiment 1) and a more traditionally formatted vigilance task (Experiment 2) using novel word stimuli (text-speak) and normally spelt words. This enabled us to address whether the SART is a better measure of sustained attention or of response strategy, and to investigate the cognitive demands of text-speak processing. In Experiment 1, 72 participants completed a subset (text-speak) and a word SART, as well as a self-reported text experience questionnaire. Those who reported more proficiency and experience with text-speak made more errors on the subset SART, but this appeared to be due to their increase in response speed. This did not occur in the word SART. In Experiment 2, 14 participants completed high No-Go, low-Go (more traditional response format) versions of these tasks to further investigate the cognitive demands of text-speak processing. Response latency increased over periods of watch only for the text-speak task, not for the word task. The results of Experiment 1 support the perspective that the SART is highly sensitive to response strategy, and the results of both experiments together indicate target detection tasks may be a novel way of investigating the cognitive demands of text-speak processing. PMID- 22052189 TI - A set of miRNAs participates in the cellular senescence program in human diploid fibroblasts. AB - Here we show that replicative senescence in normal human diploid IMR90 fibroblasts is accompanied by altered expression of a set of microRNAs (miRNAs) (senescence-associated miRNAs), with 14 and 10 miRNAs being either up or downregulated (>2-fold), respectively, in senescent with respect to young cells. The expression of most of these miRNAs was also deregulated upon senescence induced by DNA damage (etoposide) or mild oxidative stress (diethylmaleate). Four downregulated miRNAs were part of miRNA family-17, recently associated to human cell and tissue aging. Moreover, eight upregulated and six downregulated miRNAs mapped in specific chromosomal clusters, suggesting common transcriptional regulation. Upon adoptive overexpression, seven upregulated miRNAs induced the formation of senescence-associated heterochromatin foci and senescence-associated beta-galactosidase staining (P<0.05), which was accompanied, in the case of five of them, by reduced cell proliferation. Finally, miR-210, miR-376a(*), miR-486 5p, miR-494, and miR-542-5p induced double-strand DNA breaks and reactive oxygen species accumulation in transfected cells. In conclusion, we have identified a set of human miRNAs induced during replicative and chemically induced senescence that are able to foster the senescent phenotype by prompting DNA damage. PMID- 22052190 TI - POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway. AB - Vascular cell senescence, induced by the DNA damage response or inflammatory stress, contributes to age-associated vascular disease. Using complementary DNA microarray technology, we found that the level of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is downregulated during endothelial cell (EC) senescence. PATZ1 may have an important role as a transcriptional repressor in chromatin remodeling and transcription regulation; however, the role of PATZ1 in EC senescence and vascular aging remains unidentified. Knockdown of PATZ1 in young cells accelerated premature EC senescence, which was confirmed by growth arrest, increased p53 protein level and senescence-associated beta-galactosidase (SA-beta-gal) activity, and repression of EC tube formation. In contrast, overexpression of PATZ1 in senescent cells reversed senescent phenotypes. Cellular senescence induced by PATZ1 knockdown in young cells was rescued by knockdown of p53, but not by knockdown of p16(INK4a). PATZ1 knockdown increased ROS levels, and pretreatment with N-acetylcysteine abolished EC senescence induced by PATZ1 knockdown. Notably, PATZ1 immunoreactivity was lower in ECs of atherosclerotic tissues than those of normal arteries in LDLR(-/-) mice, and immunoreactivity also decreased in ECs of old human arteries. These results suggest that PATZ1 may have an important role in the regulation of EC senescence through an ROS-mediated p53-dependent pathway and contribute to vascular diseases associated with aging. PMID- 22052191 TI - A quarter century of granzymes. AB - Granzymes (Grs) were discovered just over a quarter century ago. They are produced by cytotoxic T cells and natural killer cells and are released upon interaction with target cells. Intensive biochemical, genetic, and biological studies have been performed in order to study their roles in immunity and inflammation. This review summarizes research on the family of Grs. PMID- 22052192 TI - Glucocorticoid-induced TNF receptor-triggered T cells are key modulators for survival/death of neural stem/progenitor cells induced by ischemic stroke. AB - Increasing evidences show that immune response affects the reparative mechanisms in injured brain. Recently, we have demonstrated that CD4(+)T cells serve as negative modulators in neurogenesis after stroke, but the mechanistic detail remains unclear. Glucocorticoid-induced tumor necrosis factor (TNF) receptor (GITR), a multifaceted regulator of immunity belonging to the TNF receptor superfamily, is expressed on activated CD4(+)T cells. Herein, we show, by using a murine model of cortical infarction, that GITR triggering on CD4(+)T cells increases poststroke inflammation and decreases the number of neural stem/progenitor cells induced by ischemia (iNSPCs). CD4(+)GITR(+)T cells were preferentially accumulated at the postischemic cortex, and mice treated with GITR stimulating antibody augmented poststroke inflammatory responses with enhanced apoptosis of iNSPCs. In contrast, blocking the GITR-GITR ligand (GITRL) interaction by GITR-Fc fusion protein abrogated inflammation and suppressed apoptosis of iNSPCs. Moreover, GITR-stimulated T cells caused apoptosis of the iNSPCs, and administration of GITR-stimulated T cells to poststroke severe combined immunodeficient mice significantly reduced iNSPC number compared with that of non-stimulated T cells. These observations indicate that among the CD4(+)T cells, GITR(+)CD4(+)T cells are major deteriorating modulators of poststroke neurogenesis. This suggests that blockade of the GITR-GITRL interaction may be a novel immune-based therapy in stroke. PMID- 22052193 TI - Cell death by autophagy: facts and apparent artefacts. AB - Autophagy (the process of self-digestion by a cell through the action of enzymes originating within the lysosome of the same cell) is a catabolic process that is generally used by the cell as a mechanism for quality control and survival under nutrient stress conditions. As autophagy is often induced under conditions of stress that could also lead to cell death, there has been a propagation of the idea that autophagy can act as a cell death mechanism. Although there is growing evidence of cell death by autophagy, this type of cell death, often called autophagic cell death, remains poorly defined and somewhat controversial. Merely the presence of autophagic markers in a cell undergoing death does not necessarily equate to autophagic cell death. Nevertheless, studies involving genetic manipulation of autophagy in physiological settings provide evidence for a direct role of autophagy in specific scenarios. This article endeavours to summarise these physiological studies where autophagy has a clear role in mediating the death process and discusses the potential significance of cell death by autophagy. PMID- 22052194 TI - Ultrafast electron-phonon coupling in hollow gold nanospheres. AB - Electronic energy relaxation in hollow gold nanospheres (HGNs) was studied using femtosecond time-resolved transient absorption spectroscopy. A range of HGNs having outer diameter-to-shell thickness aspect ratios of 3.5 to 9.5 were synthesized by a galvanic replacement method. The HGNs exhibited electron-phonon relaxation times that decreased from 1.18 +/- 0.16 to 0.59 +/- 0.08 ps as the aspect ratio increased over this range. The corresponding electron-phonon coupling constants, G, ranged from (1.67 +/- 0.22) to (3.33 +/- 0.45) * 10(16) W m(-3) K(-1). Electron-phonon coupling was also determined for solid gold nanospheres (SGNs) with diameters spanning 20 nm to 83 nm; no size dependence was observed for these structures. The HGNs with high aspect ratios exhibited larger electron-phonon coupling constants than the SGNs, whose average G value was (1.9 +/- 0.2) * 10(16) W m(-3) K(-1). By comparison, low-aspect ratio HGNs exhibited values comparable to SGNs. The electron-phonon coupling of high-aspect ratio HGNs was also influenced by the surrounding fluid dielectric; slightly smaller G values were obtained when methanol was the solvent as opposed to water. This coupling enhancement observed for high-aspect ratio HGNs was attributed to the large surface to volume ratio of these structures, which results in non negligible contributions from the environment. PMID- 22052195 TI - The targeted delivery of IL17 to the mouse tumor neo-vasculature enhances angiogenesis but does not reduce tumor growth rate. AB - There has been a long controversy as to whether interleukin-17 (IL17) has an impact on tumor growth. In order to assess whether IL17 may affect tumor growth, it would be convenient to achieve high levels of this pro-inflammatory cytokine at the tumor neo-vasculature, since IL17 is known to promote angiogenesis. Here, we have generated and tested in vivo a fusion protein, consisting of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin, a marker of angiogenesis) and of murine IL17 (mIL17). The resulting immunocytokine (termed F8-mIL17) was shown to selectively localize at the tumor neo-vasculature and to vigorously promote tumor angiogenesis, without however reducing or enhancing tumor growth rate both in immunocompetent and in immunodeficient mice. PMID- 22052196 TI - Notch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinoma. AB - Notch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways. Aberrant high expression of Notch1 was significantly associated with metastatic disease parameters in HCC patients, such as tumor-node-metastasis Stages III-IV and tumor venous invasion. Knocking-down Notch1 reduced cell motility in vitro and orthotopic tumor metastasis from the liver to the lung in vivo in a mouse model. In metastatic HCC cells, abnormal expression of Notch1 was associated with increased expression of Snail1 and repressed expression of E cadherin; the Notch1-Snail1-E-cadherin association can also be found in HCC patient tumors. Inhibition of Notch1 by shRNA abolished Snail1 expression, which further resulted in the re-establishment of repressed E-cadherin in metastatic HCC cells. Thus, abnormal Notch1 expression was strongly associated with HCC metastatic disease, which might be mediated through the Notch1-Snail1-E-cadherin pathway. Knock-down of Notch1 reversed HCC tumor metastasis in a mouse model. Therefore, these data suggest that effective targeting of Notch signaling might also inhibit tumor metastasis. PMID- 22052197 TI - Gastroesophageal reflux after vertical banded gastroplasty is alleviated by conversion to gastric bypass. AB - BACKGROUND: Conversion operations after vertical banded gastroplasty (VBG) are sometimes performed because of vomiting and/or acid regurgitation. Primary operation with gastric bypass (GBP) is known to reduce gastroesophageal reflux (GERD). Previous studies have not been designed to differentiate between the effects of the altered anatomy and of the ensuing weight loss. No series has reported data on acid reflux before and after conversion from VBG to GBP. METHODS: We invited eight VBG patients with current symptoms of GERD. All had intact staple lines as assessed by barium meal and gastroscopy. Acid reflux was quantified using 48-h Bravo capsule measurements. Conversion operations were performed creating an isolated 15-20-ml pouch; the previously banded part of gastric wall was excised. Gastrojejunostomy was made end to end with a 28-mm circular stapler. The study is based on five patients consenting to early postoperative endoscopy and pH measurement. RESULTS: All patients were women with a mean age of 49.5 years and BMI of 36.3. Time since VBG was 132.1 months. Time from conversion to second measurement was 46.6 days and BMI at that time 32.7. There was no mortality and no serious morbidity. All patients improved clinically and no patient had to go back on proton pump inhibition or antacids. Total time with pH < 4.0 was reduced from 18.4% to 3.3% (p < 0.05). DeMeester score was reduced from 58.1 to 15.9 (p < 0.05). CONCLUSIONS: The effect of converting VBG operated patients to GBP results in a near-normalisation of acid reflux parameters and a discontinuation of proton pump inhibitor medication. PMID- 22052198 TI - Can a protocol for glycaemic control improve type 2 diabetes outcomes after gastric bypass? AB - BACKGROUND: Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment for patients with type 2 diabetes (T2DM). Tight glycaemic control immediately after RYGB for T2DM may improve long-term glycaemic outcomes, but is also associated with a higher risk of hypoglycaemia. We designed a treatment algorithm to achieve optimal glycaemic control in patients with insulin-treated T2DM after RYGB and evaluated its feasibility, safety and efficacy. METHODS: Fifty patients following protocol-driven diabetes management were discharged on a fixed amount of metformin and glargine, with the insulin dose adjusted according to a standardised insulin sliding scale aiming for a fasting capillary glucose (FCG) of 5.5-6.9 mmol/L. Glycaemic outcome and remission of diabetes (defined as HbA1c < 6% and FCG levels < 5.6 mmol/L for at least 1 year without hypoglycaemic medication) were compared between patients who received protocol-driven treatment and a similar cohort of 49 patients following standard glycaemic management. RESULTS: At 1 year follow-up, the protocol-driven group showed a greater improvement in glycaemic control than the non-protocol-driven group (HbA1c -3.0 +/- 0.2% vs. -1.2 +/- 0.1%, P < 0.001; FCG levels -3.4 +/- 0.2 vs. -2.0 +/- 0.2 mmol/L, P = 0.02) and a higher remission rate from T2DM (50.0% vs. 6.1%, P < 0.001). No symptomatic hypoglycaemia was reported in either group. CONCLUSIONS: The protocol-driven management proved to be feasible, safe and effective in achieving targeted glycaemic control in T2DM after RYGB. The next step will be to scrutinise the efficacy of protocol-driven management in a randomised controlled clinical trial. PMID- 22052199 TI - Prevalence of endocrine disorders in morbidly obese patients and the effects of bariatric surgery on endocrine and metabolic parameters. AB - BACKGROUND: Several endocrine abnormalities, including hypothyroidism and Cushing's syndrome (CS), are considered as causative factors of obesity. The aim of this study was to evaluate the prevalence of endocrine disorders and obesity associated co-morbidities, as well as the impact of substantial weight loss. METHODS: Screening was performed in 433 consecutive morbidly obese patients (age 41 +/- 12 years; BMI 47 +/- 6.9 kg/m(2); women 76%). A 1-mg dexamethasone suppression test (1-mg DST) was conducted to exclude CS, and thyrotropin (TSH) was measured to exclude hypothyroidism. Insulin sensitivity was estimated from oral glucose tolerance tests employing the Clamp-like index. Examinations were carried out at baseline, as well as at 6 and 12 months postoperatively. RESULTS: The prevalence of CS was below 0.6%. Before surgery, TSH was elevated compared to an age- and sex-matched normal weight control group (2.4 +/- 1.2 vs. 1.5 +/- 0.7 MUU/ml; p < 0.001). The NCEP criteria of metabolic syndrome (MetS) were fulfilled by 39.5% of the patients. Impaired glucose tolerance and diabetes mellitus were observed in 23.5% and 22.6%, respectively. Seventy-two percent were insulin resistant. During follow-up, weight (BMI 47 +/- 6.9 vs. 36 +/- 6.4 vs. 32 +/- 6.6 kg/m(2); p < 0.001) and TSH decreased significantly (2.4 +/- 1.2 vs. 1.8 +/- 1.0 vs. 1.8 +/- 1.0 MUU/ml; p < 0.001). Serum cortisol was higher in the MetS(+) group compared to the MetS(-)-group (15.0 +/- 6.3 vs. 13.5 +/- 6.3 MUg/dl; p = 0.003). CONCLUSIONS: CS appears to be a rare cause of morbid obesity. Normalization of slightly elevated thyrotropin after weight loss suggests that obesity causes TSH elevation rather than the reverse. PMID- 22052200 TI - Typing of renal tumors by morphological and immunocytochemical evaluation of fine needle aspirates. AB - Image-guided fine needle aspiration biopsy (FNAB) of renal masses can accurately evaluate malignancy. Adjunct methods are needed for accurate typing of renal cell carcinomas (RCC) and benign neoplasms. Cytopathological diagnoses of 79 routine ultrasound-guided FNAB of renal lesions were compared to consequent histological diagnosis and size of tumors. Cytology samples were sufficient for immunocytochemical subtyping in 43 cases (54.4%). The median tumor size was 2.8 cm, with 57 cases (76%) smaller than or equal to 4 cm. When a panel of immunocytochemical stainings (vimentin, CK7, CD117, P504S) was applied, accurate diagnoses were obtained in 11/12 (91.7%) of clear cell RCC (CRCC), 14/17 (82.3%) of papillary RCC (PRCC) and 5/7 (71.4%) of chromophobe RCC (ChRCC), respectively. Substantial cell pleomorphism with unusual immunostainings led to erroneous diagnosis of pheochromocytoma in CRCC with eosinophilic cytoplasm. Only 30% of CRCC were correctly diagnosed in the group without immunostaining, seven were suspicious for CRCC, and the remainder had unrepresentative material for CRCC. Cytopathological diagnoses were less accurate in oncocytomas (n=11), regardless of immunocytochemical staining. Cystic nephromas (n=2) and MEST (n=1) were overdiagnosed as suspicious and positive for PRCC, respectively, with immunocytochemical staining not assisting in correct diagnosis. RCC can be accurately typed as CRCC, PRCC or ChRCC in fine needle aspirates in a routine clinical setting if the cellular material is sufficient and a panel of antibodies is used (vimentin, CK7, P504S, CD117). The classification of oncocytomas and cystic nephromas is not reliable since atypical morphology and immunocytochemical reactions overlap with RCC. PMID- 22052201 TI - Igf2-derived intronic miR-483 promotes mouse hepatocellular carcinoma cell proliferation. AB - Most intronic micro-RNAs are coexpressed with their host genes, suggesting that they may play similar roles. The function of miR-483 remains unknown, although it is embedded in an intron of Igf2 gene, which is an activator of hepatocellular carcinoma proliferation. In the present study, we provide evidence that Igf2 derived miR-483 can induce proliferation in hepatocellular carcinoma cells. The miR-483 promotion of proliferation was analysed by soft agar colony formation assay and proliferation curve assay. The effect of miR-483 on Socs3 expression was examined by Western blot and a reporter assay. Our results revealed that Igf2 derived intronic miR-483 was identified by the application of 94G6, an inhibitor of Igf2 at the transcriptional level. All results from the (3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) MTT assay, the proliferation curve assay and the soft agar colony formation assay showed that miR-483 promoted the proliferation of hepatocellular carcinoma cells. Finally, Socs3, a putative target predicted by bioinformatics, was regulated by miR-483 at mRNA and protein levels. Direct binding with the 3' UTR was identified by a luciferase activity assay. Our findings demonstrate that Igf2-derived intronic miR-483, through downregulation of its target Socs3, regulates hepatoma cell proliferation and thus may serve as a potential target for hepatocellular carcinoma therapy. PMID- 22052203 TI - Expanding the individual health insurance market. AB - Faced with rapidly escalating premiums, fewer offers of insurance and, in some cases, a collapsing individual market, states adopted reforms designed to make coverage more affordable and available in the non-group market. This synthesis looks at the evidence of the effectiveness of state reforms. Key findings include: Comprehensive underwriting reforms, including guaranteed issue, guaranteed renewal, and limits on pre-existing conditions, did make insurance more available. In states with guaranteed issue and community rating, average premiums for the entire pool rose, while premiums fell for higher-risk people. There was some impact from adverse selection but not as much as anticipated. Risk spreading mechanisms, but many high-risk people still could not afford insurance, so the impact from their potential influx was muted. Overall, states with comprehensive reform saw a decrease in the proportion of people insured, as healthier people left the market. There is some limited evidence that more high risk people were covered. PMID- 22052202 TI - Identification of PLSCR1 as a protein that interacts with RELT family members. AB - Receptor expressed in lymphoid tissues (RELT) proteins are recently described surface receptors belonging to the larger TNF receptor family. To improve our understanding of RELT-mediated signal transduction, we performed a screen for RELT-interacting proteins. Phospholipid Scramblase 1 (PLSCR1) was identified through a yeast two-hybrid genetic screen utilizing the intracellular portion of the RELT family member, RELL1, as bait. PLSCR1 was observed to physically interact with all known RELT family members as determined by co immunoprecipitation experiments. The protein kinase, oxidative stress responsive 1 (OSR1) was previously shown to interact and phosphorylate all three RELT family members. In our study, no physical association was observed between OSR1 and PLSCR1 alone. However, in the presence of RELT, OSR1 was capable of co immunoprecipitating PLSCR1, suggesting the formation of a protein complex between RELT, OSR1, and PLSCR1. In addition, OSR1 phosphorylated PLSCR1 in an in vitro kinase assay, but only in the presence of RELT, suggesting a functional multiprotein complex. RELT and PLSCR1 co-localized in intracellular regions of human embryonic kidney-293 cells, with RELT overexpression appearing to alter the localization of PLSCR1. These studies demonstrate that RELT family members physically interact with PLSCR1, and that these interactions may regulate the phosphorylation of PLSCR1 by OSR1. PMID- 22052205 TI - Care management of patients with complex health care needs. AB - Patients with complex health care needs account for a high percentage of annual medical expenditures. Care management is a set of activities intended to improve patient care and reduce the need for medical services by helping patients and caregivers more effectively manage health conditions. This synthesis reviews the evidence on care management and its ability to improve patient care and reduce costs. Key findings include: care management can improve quality of care, although it takes time; studies that followed patients longer were more likely to reveal improvements. Care management's impact on cost reduction is less consistent. Programs that support patient transitions from hospital-to-home were the most successful because they reduced hospital readmissions. Care management within primary care settings may also generate savings. Elements of effective programs include: good identification of patients who could benefit from care management; specially-trained RN/care managers with low patient loads, working with physicians and a multidisciplinary team; and in-person patient contact. Finally, the current fee-for-service systems present barriers to widespread use of care management. PMID- 22052204 TI - Long-term voluntary exercise, representing habitual exercise, lowers visceral fat and alters plasma amino acid levels in mice. AB - OBJECTIVES: To determine the impact of long-term voluntary exercise, representing habitual exercise for the prevention of lifestyle-related diseases, on glucose, lipid, and amino acid metabolism in mice. METHODS: Twenty-four mice aged 6 weeks were divided into three groups. Two groups (16 mice) were housed individually in either cages equipped with a running wheel (8 mice, exercising, Ex-mice) or without (8 mice, sedentary, Se-mice) for 24 weeks. The remaining group (8 mice) was sacrificed at 6 weeks of age. Biomarkers related to glucose, lipid, and amino acid metabolism were examined. RESULTS: Ex-mice ran voluntarily, predominantly in the dark. The distance per day peaked at 4 weeks and then decreased until 12 weeks to around the level seen at the beginning of the experimental period, and was maintained at 4.9 +/- 0.2 km/day from 12 to 24 weeks. Ex-mice showed a similar adrenal weight and vitamin C content to Se-mice but had a significantly lower body weight and higher food intake. Ex-mice also showed a higher skeletal muscle weight, a lower white adipose tissue and liver weight, associated with lower plasma leptin and insulin-like growth factor-1 levels, and a lower hepatic triglyceride content. Analysis of plasma amino acids showed that Ex-mice had significantly higher phenylalanine, tyrosine, and glutamine levels, resulting in a significantly lower Fischer's ratio. CONCLUSIONS: We present an animal model of long-term voluntary exercise under low stress. Findings related to the effects of long-term voluntary exercise on lipid, and amino acid metabolism in our mouse model indicate that such an exercise regimen may affect pathophysiological states related to appetite and behavior. PMID- 22052206 TI - The pedicle-facet angle and tropism in the sagittal plane in degenerative spondylolisthesis: a computed tomography study using multiplanar reformations techniques. AB - STUDY DESIGN: A case-control study. OBJECTIVE: To analyze the facet joint orientation in the sagittal plane [pedicle-facet angle (P-F angle)] and facet tropism, and clarify the relationship between P-F angle and the amount of vertebral slipping in degenerative spondylolisthesis (DS) patients on multislice computed tomography using multiplanar reformations techniques. SUMMARY OF BACKGROUND DATA: Some studies have indicated a correlation between DS and an increased sagittal orientation of the facet joints. However, the facet orientation has not been fully elucidated and it had been measured only in the transverse plane of computed tomography and magnetic resonance imaging. Although the P-F angle had been measured on the plain radiographs, accurate measurement was difficult to obtain because of the technical limitations. METHODS: A total of 156 patients, who came to our hospital for low back pain and/or sciatica were divided into 2 groups. The DS group comprised of 78 patients with DS at L4-L5, and the control group comprised of 78 patients without spondylolisthesis. The P-F angle and tropism were measured in the sagittal plane on multi-slice computed tomography using multiplanar reformations techniques. RESULTS: The P-F angles at L4-L5 were 117.02+/-6.89 degrees (left), 115.95+/-6.02 degrees (right) in the DS group and 106.71+/-3.19 degrees (left), 105.58+/-3.07 degrees (right) in the control group, respectively (P1<0.01, P(r)<0.01). The facet tropism at L4-L5 in the DS group was significantly increased, compared with that in the control group (P=0.004). The mean P-F angle at L4-L5 did not correlate with the amount of vertebral slipping (r=0.176, P=0.122). CONCLUSIONS: The P-F angle was the highest at L4-L5 both in the DS and the control group, which might explain the fact that L4 vertebra is more likely to slip forward. The P-F angle of the slipped vertebra alone was more horizontally inclined and facet tropism in the sagittal plane may relate well to DS. PMID- 22052207 TI - S-allylcysteine induces cell cycle arrest and apoptosis in androgen-independent human prostate cancer cells. AB - To increase the use of phytochemical supplements as chemoprevention or adjuvant drugs in cancer treatment, it is necessary to verify their biological effects and correlative mechanisms. Recently, S-allylcysteine (SAC) was identified as a potent compound derived from garlic. The aim of this study was to evaluate the anticancer effects of SAC on androgen-independent human prostate cancer (PC-3) cells and to elucidate the possible mechanisms. PC-3 cells were incubated with SAC at three different concentrations. Cell growth was determined by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assay. Cell cycle and apoptosis were determined by flow cytometric assay. The expression of apoptosis-related molecules was detected by Western blot analysis. We found that SAC suppressed the proliferation of PC-3 cells and led to cell cycle arrest at the G0/G1 phases, as well as inducing cell apoptosis which was accompanied by the decreased expression of Bcl-2 and increased expression of Bax and caspase 8. This study demonstrated the chemopreventive activity of SAC in vitro, and that SAC may be a promising candidate for prostate cancer treatment. PMID- 22052208 TI - Evaluating ring-tailed lemurs (Lemur catta) from southwestern Madagascar for a genetic population bottleneck. AB - In light of historical and recent anthropogenic influences on Malagasy primate populations, in this study ring-tailed lemur (Lemur catta) samples from two sites in southwestern Madagascar, Beza Mahafaly Special Reserve (BMSR) and Tsimanampetsotsa National Park (TNP), were evaluated for the genetic signature of a population bottleneck. A total of 45 individuals (20 from BMSR and 25 from TNP) were genotyped at seven microsatellite loci. Three methods were used to evaluate these populations for evidence of a historical bottleneck: M-ratio, mode-shift, and heterozygosity excess tests. Three mutation models were used for heterozygosity excess tests: the stepwise mutation model (SMM), two-phase model (TPM), and infinite allele model (IAM). M-ratio estimations indicated a potential bottleneck in both populations under some conditions. Although mode-shift tests did not strongly indicate a population bottleneck in the recent historical past when samples from all individuals were included, a female-only analysis indicated a potential bottleneck in TNP. Heterozygosity excess was indicated under two of the three mutation models (IAM and TPM), with TNP showing stronger evidence of heterozygosity excess than BMSR. Taken together, these results suggest that a bottleneck may have occurred among L. catta in southwestern Madagascar in the recent past. Given knowledge of how current major stochastic climatic events and human-induced change can negatively impact extant lemur populations, it is reasonable that comparable events in the historical past could have caused a population bottleneck. This evaluation additionally functions to highlight the continuing environmental and anthropogenic challenges faced by lemurs in southwestern Madagascar. PMID- 22052209 TI - Educational paper: Retinopathy of prematurity. AB - Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the premature infant with an incompletely vascularized retina. The spectrum of ophthalmological findings in ROP exists from minimal sequelae, which do not affect vision, to bilateral retinal detachment and total blindness. With the increased survival of very small infants, retinopathy of prematurity has become one of the leading causes of childhood blindness. Over the past two decades, major advances have been made in understanding the pathogenesis of ROP, to a large extent as a result of changes in clinical risk factors (oxygen and non oxygen related) and characteristics observed in ROP cases. This article provides a literature review on the evolution in clinical characteristics, classification and treatment modalities and indications of ROP. Special attention is hereby paid to the neonatal factors influencing the development of ROP and to the necessity for everyone caring for premature babies to have a well-defined screening and treatment protocol for ROP. Such screening protocol needs to be based on a unit specific ROP risk profile and, consequently, may vary between different European regions. CONCLUSION: Retinopathy of prematurity is an important cause of ocular morbidity and blindness in children. With better understanding of the pathogenesis, screening and treatment guidelines have changed over time and are unit specific. PMID- 22052210 TI - Public program crowd-out of private coverage. AB - Coverage expansions by Medicaid, SCHIP and other state programs significantly increased the number of people covered by public insurance. Crowd-out occurs when people drop private coverage for public coverage, when those enrolled in public insurance turn down private coverage when eligible, or when employers opt not to offer private insurance because of the existence of a public program. This synthesis examines the extent of crowd-out and whether it can be reduced. Key findings include: Estimates of crowd-out are imprecise and vary depending on the type of coverage expansion; the assumptions, methods and data used; and the time period covered. Crowd-out is more likely to occur in programs that enroll families, and among families with incomes greater than 200 percent FPL. Programs have used waiting periods and cost-sharing to limit crowd-out, but these techniques can be difficult and costly to implement, and may reduce program participation by the uninsured. PMID- 22052211 TI - Creating stories to live by: caring and professional identity formation in a longitudinal integrated clerkship. AB - Building on other models of longitudinal integrated clerkships (LIC), the University of Alberta developed its Integrated Community Clerkship with guiding principles of continuity of care, preceptor and learning environment. Professionalism is an important theme in medical education. Caring is important in professional identity formation and an ethic of caring is a moral framework for caring. This study explored the development of an ethic of caring in an LIC using empathy, compassion and taking responsibility as descriptors of caring. Through a hermeneutic phenomenological study, the authors focused on students' accounts of being with patients. Following an iterative process of successive analyses and explorations of the relevant literature, sensitizing concepts related to physician identity, and an ethic of caring were used to make sense of these accounts following the principles of constructivist grounded theory methodology. Continuity afforded by the LIC results in a safe environment in which students can meaningfully engage with patients and take responsibility for their care under the supervision of a physician teacher. Together these attributes foster an emerging physician identity born at the site of patient student interaction and grounded in an ethic of caring. A medical student's evolving professional identity in the clerkship includes the emergence of an ethic of caring. Student accounts of being with patients demonstrate that the LIC at the University of Alberta affords opportunities for students be receptive to and responsible for their patients. This ethic of caring is part of an emerging physician identity for the study participants. PMID- 22052212 TI - Theoretical study of the conformational and optical properties of a fluorescent dye. A step toward modeling sensors grafted on polymer structures. AB - The conformational and photophysical properties in toluene solution of a naphthoic acid derivative, namely 4-naphthoyloxy-1-methoxy-2,2,6,6 tetramethylpiperidine, which can simulate a pendant active group grafted on apolar polymer structures, were studied by means of calculations based on the density functional theory (DFT) and its time-dependent extension (TD-DFT) coupled to a polarizable continuum model (PCM) of the surrounding medium. The conformational landscape was exhaustively explored and the conformers responsible for the absorption and emission spectra were identified through well established computational procedures based on a tuned combination of functional (PBE0) and basis set (N07D) which reproduced satisfactorily the experimental absorption and emission wavelengths. PMID- 22052213 TI - VSV-MP gene therapy strategy inhibits tumor growth in nude mice model of human lung adenocarcinoma. AB - Vesicular stomatitis virus (VSV) matrix protein (MP) can induce in vitro apoptosis of tumor cells in the absence of other viral components. Here, the antitumor activity of VSV-MP against lung adenocarcinoma was investigated in vivo. A pVAX-plasmid DNA encoding VSV-MP and control empty vectors (pVAX) were constructed and wrapped-up with liposome. A549 and Spc-A1 human lung adenocarcinoma cells were transfected with liposomal-VSV-MP (Lip-MP) or Lip-pVAX and then examined for cell viability or apoptosis using Hoechst/propidium iodide staining by flow cytometry, and further demonstrated by caspase/poly ADP-ribose polymerase (PARP) cleavage analysis. For the in vivo study, A549 and Spc-A1 lung carcinoma models in nude mice were established and randomly assigned into three groups to receive eight 2-weekly intravenous administrations of medium alone as control, Lip-pVAX or Lip-MP, respectively. Subsequently, Lip-MP significantly reduced tumor growth and prolonged the survival of tumor-bearing mice compared with Lip-pVAX and control agents (P<0.05), with much higher apoptosis index of both in vivo and in vitro tumor cells, respectively (P<0.05). In addition, in vivo antitumoral effect was associated with natural killer-(NK) cell congregation without evidence of toxicity. These observations suggest that systemically delivering Lip-MP has a specific dual antitumor activity in human lung adenocarcinoma by inducing apoptosis and possibly stimulating NK-cell responses, it may provide a clue for developing new therapeutic approaches against human lung adenocarcinoma. PMID- 22052214 TI - Evolution of Salmonella nomenclature: a critical note. AB - Salmonellae are widely distributed but nomenclaturally controversial pathogens of both humans and animals. Despite elaborate studies, much still remain to be discovered about these organisms. Although Salmonella nomenclature has proved to be rather complex, in 2005, Salmonella enterica finally gained official approval as the type species of the genus Salmonella. In addition, one other species has been approved and recognised in the genus Salmonella, namely, Salmonella bongori. New serovars (serotypes) are continually being discovered each year and reported in the journal Research in Microbiology. Salmonella serovars and their antigenic formulae are listed in the White-Kauffmann-Le Minor scheme and updated by the World Health Organization's Collaborating Centre for Reference and Research on Salmonella at the Pasteur Institute, Paris, France. PMID- 22052215 TI - The role of family factors and school achievement in the progression of adolescents to regular smoking. AB - This study examines whether parental smoking and single parenting were related to adolescents' school achievement and anti-smoking parental practices as well as how these factors predicted later smoking. The sample comprised 1163 Finnish students in Grades 7 through 9. Results show that at the beginning of the seventh grade, parental smoking and single parenting were related to adolescents' lower levels of school achievement. Moreover, parental smoking had moderate association with lack of house smoking rules. At the beginning of the ninth grade, these associations were strengthened and lack of house smoking rules as well as loosened perceived parental punishment for smoking was related to both parental smoking and single parenting. The likelihood of ninth grade regular smoking was greater among adolescents whose parents smoked, who had no smoking rules in their homes and had substandard school achievement. These results suggest that smoking parents and single parents had similar anti-smoking regulations for their children at the baseline but once children became older smoking parents were not able to maintain these rules as successfully as non-smoking parents and families with two parents. Motivating parents to uphold these anti-smoking regulations offers a prospective intervention opportunity. PMID- 22052216 TI - A randomized trial to promote health belief and to reduce environmental tobacco smoke exposure in pregnant women. AB - Exposure to environmental tobacco smoke (ETS) is widespread among women in Iran. This study aimed to explore the impact of education on health belief and environmental tobacco smoke exposure in pregnant women. This randomized trial was administrated to 130 pregnant women exposed to ETS. The face-to-face education was provided for the intervention group after completing the questionnaire compiled on the constructs of the health belief model and self-reports of weekly ETS exposure. The theoretical constructs and weekly ETS exposure were compared in the study groups at the intake, third, fourth and fifth sections. In the intervention group, perceived susceptibility/severity and perceived benefits increased and the weekly ETS exposure decreased on the third as opposed to the first section (P < 0.05). Perceived susceptibility/severity and benefits significantly correlated with weekly ETS exposure in the intervention group (P < 0.05). The findings of this study point to the fact that education about the impacts of ETS exposure of pregnant women is an effective way to increase the theoretical constructs according to the health belief model and is associated with a reduction of ETS exposure. But this is not sufficient for making smoke free homes. PMID- 22052217 TI - Evidence of the adoption and implementation of a statewide childhood obesity prevention initiative in the New York State WIC Program: the NY Fit WIC process evaluation. AB - Process evaluations are critical in determining whether outcome evaluations are warranted. This study assessed the extent to which a childhood obesity prevention initiative, NY Fit WIC, was adopted and implemented by the New York State Supplemental Nutrition Program for Women, Infants and Children (WIC). Process data came from qualitative telephone interviews of 101 WIC local agency directors, following NY Fit WIC trainings. Activities were summarized and cross tabulated by target level (i.e. participant, staff, agency or community) and by theoretical construct (i.e. knowledge promotion, skill building, self-efficacy or role modeling). Approximately 528 activities were reported across all WIC agencies. When activities were grouped into similar categories, 123 unique activities were identified. Agencies were more likely to implement physical activity-related activities (67%) than nutrition-related activities (33%). The majority of activities targeted WIC participants (47%) and staff (22%) and focused on skill building/self-efficacy (67%) among participants and on role modeling (61%) among staff. The involvement of all agencies shows a high level of adoption of the initiative. The diverse number of activities suggests that WIC local agencies tailored implementation to match their resources and clients' needs as planned. These results suggest that an outcome evaluation is warranted to determine whether meaningful behavioral changes occurred among WIC participants and staff. PMID- 22052218 TI - An assessment of cost, quality and outcomes for five HIV prevention youth peer education programs in Zambia. AB - Youth peer education (YPE) programs are a popular strategy for HIV prevention in sub-Saharan Africa. However, research on the effectiveness of YPE programs is scarce and the wide variation in programs makes it difficult to generalize research findings. Measuring quality and comparing program effectiveness require the use of standardized instruments. In this study, we used standardized evidenced-based instruments to compare program inputs, quality, outputs and outcomes for five YPE programs in Zambia. Clinic surveys were used to measure the following program outcomes: young people's exposure to the YPE programs and referrals of young people to clinics for HIV/sexually transmitted infection (STI) testing and other reproductive health services. The study revealed wide variation in the cost, quality and outcomes of YPE programs. Higher quality programs were associated with greater exposure and more referrals of youth to the clinics. However, one of the two highest quality programs achieved twice as many exposure and referral outcomes at about half the cost per peer educator of the more expensive program. Results indicate that the standardized instruments used in this study are useful for assessing and comparing program attributes among diverse YPE programs. PMID- 22052219 TI - Mapping the route to visual awareness. AB - The "neural correlate" of perceptual awareness is much sought-after. Here, we present an novel approach to the identification of possible neural correlates, in which we exploit the temporal connection that inevitably links the selection process that determines what we become aware of, and the development of awareness itself. Because the speed of selection determines when downstream processes can first become involved in generating awareness, the latency of neural processes provides a way to isolate the neural correlates of awareness. We recorded event related potentials (ERPs) while observers carried out a visual behavioral task designed to estimate attentional selection latency. We show that within-task trial-by-trial behavioral variability in attentional selection latency correlates to trial-by-trial variability in ERP latency. This was true in a posterior contralateral region, and in central and frontal areas, thereby implicating these as waypoints along which visual information flows on the way to visual awareness. PMID- 22052220 TI - Polymorphism of the inosine triphosphate pyrophosphatase gene predicts ribavirin induced anemia in chronic hepatitis C patients. AB - Ribavirin (RBV)-induced anemia is a serious side effect of pegylated interferon (PEG-IFN) plus RBV therapy which is the standard care most effective for hepatitis C virus (HCV) infection. In the present study, we investigated the association of inosine triphosphate pyrophosphatase (ITPA) genotypes with RBV induced hemoglobin (Hb) reduction in HCV patients treated with PEG-IFN/RBV therapy. The genotypes of the ITPA rs1127354 single nucleotide polymorphism were determined in 179 patients with HCV infection. Among them, 52 patients were treated with PEG-IFN/RBV. The frequency of the ITPA major allele (CC) was 76.3% and that of the minor allele (CA and AA) was 23.7%. A rapid decrease in Hb levels during the initial 4 weeks was observed in patients with the ITPA major allele (CC), but not in patients with the ITPA minor allele (C/A and AA). Hb levels at 4 weeks were significantly lower in patients with the ITPA major allele than the levels in patients with the minor allele. Out of the 41 patients, 6 (14.6%) with ITPA major allele had Hb levels <10 g/dl and 11 patients (26.8%) had a decline in Hb of >3 g/dl. None of the patients with the ITPA minor allele had such data. There were no significant differences in virological responses of HCV-RNA between patients with the ITPA major allele and those with the minor allele. In conclusion, the ITPA genotypes may be a useful marker for prediction of RBV induced anemia. PMID- 22052221 TI - Cost-sharing: effects on spending and outcomes. AB - As health reform drives the largest expansion of health insurance since Medicare and policy-makers grapple with how to slow the increase in health care spending, cost-sharing--the division of health care costs between patients and insurers--is considered an important tool. This synthesis reviews the evidence on cost sharing. Key findings include: Research consistently shows demand for health care is price sensitive, but it is unlikely cost-sharing will significantly slow the growth of health care spending. Almost 50 percent of costs are associated with the 5 percent of the population facing serious medical conditions. Studies show these patients rely on their doctors to guide treatment decisions. Increased cost sharing may shift the financial burden from insurers and public payers to patients. Patients are not able to discern between appropriate and inappropriate care in response to increased cost-sharing. For the average person, increased cost-sharing may not adversely affect their health, but for vulnerable populations, increased cost-sharing is associated with adverse health outcomes. Low-income populations are disproportionately affected by increased cost-sharing. People in poor health respond differently to cost-sharing changes than healthy people. Finally, cost-sharing is not well-targeted on low-value services making it difficult for patients to make appropriate decisions. PMID- 22052222 TI - Long-term results of radiofrequency ablation treatment of stage I non-small cell lung cancer: a prospective intention-to-treat study. AB - INTRODUCTION: About one-fifth of patients with resectable non-small cell lung cancer (NSCLC) are unsuitable for surgical treatment. Radiofrequency ablation offers an alternative minimally invasive option. We report the result of an intention-to-treat study with long-term follow-up. METHODS: From 2001 to 2009, we performed 80 percutaneous radiofrequency ablations of 59 stage I NSCLC in 57 inoperable patients. Two patients were treated for two separate lesions. The study group consisted of 45 males and 12 females, with mean age of 74 years (range, 40-88 years). All patients had pathological evidence of NSCLC, which was in stage IA in 44 cases and in stage IB in the other 15 cases. The mean size of the lesions was 2.6 cm (range, 1.1-5 cm). Fourteen lesions were retreated up to five times. The procedure was always performed under local anesthesia and conscious sedation. Most of the procedures were performed under computed tomography guidance, with nine under ultrasonography guidance. RESULTS: In all cases, the procedure was technically successful. No mortality was recorded, and major morbidity consisted of four cases of pneumothorax requiring pleural drainage. At a mean follow-up of 47 months, the complete response rate was 59.3% (stage Ia 65.9%, stage Ib 40%, p = 0.01), with a mean local recurrence interval of 25.9 months. Median overall survival and cancer-specific survival were 33.4 and 41.4 months, respectively. Cancer-specific actuarial survival was 89% at 1 year, 59% at 3 years, and 40% at 5 years. CONCLUSIONS: Radiofrequency ablation treatment of early-stage NSCLC seems to be a effective minimally invasive therapy even in the long-term period, particularly for stage Ia tumors. PMID- 22052223 TI - Erlotinib or docetaxel for second-line treatment of non-small cell lung cancer: a real-world cost-effectiveness analysis. AB - INTRODUCTION: Erlotinib was recently approved in British Columbia (BC) as a second-line treatment for advanced NSCLC. A cost-effectiveness analysis was conducted which compares costs and effectiveness in patients who received second line erlotinib with those in patients who received docetaxel. METHODS: In a population of patients who have been treated with drugs (either erlotinib or docetaxel) for advanced NSCLC, overall survival (OS), progression-free survival (PFS), and probability of survival 1 year after beginning of second-line treatment (1YS) were determined using Kaplan-Meier and Cox proportional hazard analysis, as well as chi test. Costs were collected retrospectively from the perspective of the BC health care system. RESULTS: Incremental mean OS was 1 day, and incremental mean cost was $2891. Neither costs nor effectiveness were statistically significantly different between groups. PFS and 1YS were also nonsignificantly different. Cox proportional hazard models were used to evaluate multivariate confounding. CONCLUSIONS: Erlotinib and docetaxel are statistically equivalent in terms of treatment cost and overall survival. As treatment practice patterns change, docetaxel may become more frequently prescribed. Therefore, the choice of whether to use erlotinib or docetaxel should be based on factors relating to patient preference rather than costs or effectiveness. PMID- 22052224 TI - Association of cytidine deaminase and xeroderma pigmentosum group D polymorphisms with response, toxicity, and survival in cisplatin/gemcitabine-treated advanced non-small cell lung cancer patients. AB - BACKGROUND: Selecting patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in non-small cell lung cancer (NSCLC). Genetic variations in drug metabolism may affect the clinical response, toxicity, and prognosis of NSCLC patients treated with cisplatin/gemcitabine based therapy. PATIENTS AND METHODS: We evaluated seven single-nucleotide polymorphisms of six genes CDA Lys27Gln (A/C); CDA C435T; ERCC1 C118T; XRCC3 Thr241Met (C/T); XPD Lys751Gln (A/C); P53 Arg72Pro (G/C), and RRM1 C524T in 192 chemotherapy-naive patients with advanced NSCLC treated with cisplatin/gemcitabine-based regimen by TaqMan probe-based assays with 7300 Real Time PCR System, using genomic DNA extracted from blood samples. RESULTS: The CDA 435 T/T genotype was significantly associated with better response (p = 0.03). The CDA 435 C/T genotype was associated with a significantly increased risk of nonhematological toxicity of grade >=3 (p = 0.02) after adjusting for performance status, age, and type of treatment regimen. In the multivariate Cox model, the XPD 751 C/C genotype was a significant prognostic factor of longer progression free survival (p = 0.006). CONCLUSION: Our data suggest polymorphic variations of drug metabolic gene were associated with response and toxicity of cisplatin/gemcitabine-based therapy and progression-free survival of patients with advanced NSCLC. PMID- 22052225 TI - Randomized phase III trial of docetaxel plus carboplatin with or without levofloxacin prophylaxis in elderly patients with advanced non-small cell lung cancer: the APRONTA trial. AB - PURPOSE: To examine the effect of levofloxacin prophylaxis on infection rates during chemotherapy with docetaxel plus carboplatin in elderly patients with advanced non-small cell lung cancer. METHODS: In a randomized, double-blind, phase III study, patients (>=65 years) with untreated, histologically/cytologically proven stage IIIB/IV non-small cell lung cancer received docetaxel (75 mg/m) plus carboplatin (area under the curve 6) on day 1 every 3 weeks, plus once-daily levofloxacin (500 mg orally) or placebo on days 5 to 11. The primary end point was the rate of grade 3/4 infections or grade 1/2 infections treated with additional antibiotics. Secondary end points included overall infection rate, toxicity, overall survival, and progression-free survival. RESULTS: In total, 187 patients were randomized to levofloxacin (n = 95) or placebo (n = 92). The rate of grade 3/4 infections or grade 1/2 infections treated with additional antibiotics (intent-to-treat population) was 27.5% (95% confidence interval, 19.3-39.0%) for levofloxacin versus 36.7% (95% confidence interval, 27.1-48.0%) for placebo. Median time to first infection was 67 days for levofloxacin versus 46 days for placebo. Grade 3/4 infections occurred in 8.8% of patients in the levofloxacin group versus 26.7% for placebo. There was one grade 5 infection in each group. Grade >=3 toxicities (levofloxacin versus placebo) included leukopenia (63.2 versus 52.2%), neutropenia (62.1 versus 51.1%), dyspnea (12.6 versus 8.7%), and pain (10.5 versus 9.8%). There was no significant difference in overall survival or progression-free survival between groups. CONCLUSIONS: Levofloxacin prophylaxis reduces the rate of infection compared with placebo and is well tolerated in elderly patients receiving docetaxel plus carboplatin. PMID- 22052226 TI - S-1 plus cisplatin with concurrent radiotherapy for locally advanced non-small cell lung cancer: a multi-institutional phase II trial (West Japan Thoracic Oncology Group 3706). AB - PURPOSE: To evaluate the combination chemotherapy using oral antimetabolite S-1 plus cisplatin (SP) with concurrent thoracic radiotherapy (RT) followed by the consolidation SP for locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Patients with stage III non-small cell lung cancer, 20 to 74 years of age, and Eastern Cooperative Oncology Group performance status 0 to 1 were eligible. The concurrent phase consisted of full dose S-1 (orally at 40 mg/m/dose twice daily, on days 1-14) and cisplatin (60 mg/m on day 1) repeated every 4 weeks for two cycles with RT delivered beginning on day 1 (60 Gy/30 fractions over 6 weeks). After SP-RT, patients received an additional two cycles of SP as the consolidation phase. RESULTS: Fifty-five patients were registered between November 2006 and December 2007. Of the 50 patients for efficacy analysis, the median age was 64 years; male/female 40/10; Eastern Cooperative Oncology Group performance status 0/1, 21/29; clinical stage IIIA/IIIB 18/32; and adenocarcinoma/others 20/30. There were 42 clinical responses including one complete response with an objective response rate of 84% (95% confidence interval [CI], 71-93%). The 1- and 2-year overall survival rates were 88% (95% CI, 75-94%) and 70% (95% CI, 55-81%), respectively. The median progression-free survival was 20 months. Of the 54 patients for safety analysis, common toxicities in the concurrent phase included grade 3/4 neutropenia (26%), thrombocytopenia (9%), and grade 3 esophagitis (9%) and febrile neutropenia (9%). In one patient, grade 3 pneumonitis was observed in the consolidation phase. There were two treatment related deaths caused by infection in the concurrent phase. CONCLUSIONS: SP-RT showed a promising efficacy against locally advanced NCSLC with acceptable toxicity. PMID- 22052227 TI - Incidence and risk factors for chest wall toxicity after risk-adapted stereotactic radiotherapy for early-stage lung cancer. AB - INTRODUCTION: High local control rates are reported after stereotactic ablative body radiotherapy (SABR) in stage I non-small cell lung cancer. Toxicity is uncommon, but few reports on long-term follow-up are available. We studied the incidence of chest wall pain (CWP) and rib fractures in patients with long-term follow-up. METHODS: Between 2003 and 2009, 500 patients (530 tumors) underwent SABR using risk-adapted fractionation schemes, consisting of three fractions of 20 Gy, five fractions of 12 Gy, or eight fractions of 7.5 Gy. Toxicity data were collected in a prospective database and scored using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Chest wall volumes receiving doses of 30, 40, 45, and 50 Gy (V30 Gy-V50 Gy) and maximum dose in 2 cm of chest wall (D2 ml) were determined for patients with CWP or rib fractures (n = 57). RESULTS: With a median follow-up of 33 months, the 3-year overall survival and local control rates were 53.1% and 90.4%, respectively. CWP developed in 11.4% of patients and was severe (grade 3) in 2.0%. Rib fractures were observed in eight patients (1.6%), accompanied by CWP in seven of these patients. On multivariate analysis, patients with CWP had larger treatment volumes and shorter tumor-chest wall distances, whereas patients with rib fractures had larger tumor diameters and treatment volumes. Grade 3 CWP and rib fractures were associated with larger volumes of chest wall receiving doses of 30 to 50 Gy and rib fractures specifically with a higher maximum dose in the chest wall. CONCLUSIONS: Severe (grade 3) chest wall toxicity is uncommon after risk-adapted SABR and manifests in 2% or fewer of patients. PMID- 22052228 TI - Respiratory gating techniques for optimization of lung cancer radiotherapy. AB - PURPOSE: The primary objective of the STIC 2003 project was to compare the clinical and economic aspects of respiratory-gated conformal radiotherapy (RGRT), an innovative technique proposed to limit the impact of respiratory movements during irradiation, versus conventional conformal radiotherapy, the reference radiation therapy for lung cancer. METHODS AND MATERIALS: A comparative, nonrandomized, multicenter, and prospective cost toxicity analysis was performed in the context of this project between April 2004 and June 2008 in 20 French centers. Only the results of the clinical study are presented here, as the results of the economic assessment have been published previously. RESULTS: The final results based on 401 evaluable patients confirm the feasibility and good reproducibility of the various RGRT systems. The results of this study demonstrated a marked reduction of dosimetric parameters predictive of pulmonary, cardiac and esophageal toxicity as a result of the various respiratory gating techniques. These dosimetric benefits were mainly observed with deep inspiration breath-hold (DIBH) techniques (ABC and SDX systems), which markedly increased the total lung volume compared with the inspiration-synchronized system based on tidal volume (Real-time Position Management). These theoretical dosimetric benefits were correlated clinically with a significant reduction of pulmonary acute toxicity, and the pulmonary, cardiac, and esophageal late toxicities, especially with DIBH techniques. Pulmonary function parameters, although more heterogeneous, especially DLCO, showed a tendency to reduction of pulmonary toxicity in the RGRT group. CONCLUSIONS: RGRT seems to be essential to reduce toxicities, especially the pulmonary, cardiac, and esophageal late toxicities with the DIBH methods. PMID- 22052229 TI - Clinical implications of high MET gene dosage in non-small cell lung cancer patients without previous tyrosine kinase inhibitor treatment. AB - INTRODUCTION: Recently, two studies revealed that MET amplification was associated with secondary epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients. But it remains uncertain whether MET amplification could be related to primary TKI resistance in NSCLC because of limited data. MATERIALS AND METHODS: MET gene dosage of the tumor tissues from 208 NSCLC patients was investigated by real time quantitative polymerase chain reaction and compared with molecular and clinical features, including EGFR mutations, KRAS mutations, EGFR gene copy numbers, and patient survivals. Three copies were used as the cutoff. Among them, 25 patients were also evaluable for EGFR TKI responsiveness. RESULTS: The proportion of high MET gene dosage was 10.58% (22/208) with higher incidence in squamous cell carcinoma (11.86%) and smokers (16.18%), although the differences with adenocarcinoma and nonsmokers were nonsignificant. Coexisting EGFR mutations were identified, and the incidence (8.54%) was similar to wild type (12.0%). High MET gene dosage was significantly associated with higher tumor stage (stage I + II versus stage III + IV; p = 0.0254) and prior chemotherapy for stage III + IV adenocarcinoma patients (35.71% versus 7.41%; p = 0.0145) but not correlated with primary TKI resistance. Among the 155 surgically resectable patients (stage I to IIIA), high MET gene dosage was significantly associated with shorter median survival (21.0 months versus 47.1 months; p = 0.042) by univariate analysis. CONCLUSIONS: High MET gene dosage was not related to primary TKI resistance and the incidence was increased after chemotherapy, suggesting high MET gene dosage may also be related to chemotherapy resistance. PMID- 22052230 TI - Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a Japanese cohort. AB - INTRODUCTION: This study was performed to determine the incidence rates of resistance factors, i.e., high-level hepatocyte growth factor (HGF) expression, epidermal growth factor receptor (EGFR) T790M secondary mutation, and MET amplification, in tumors with intrinsic and acquired EGFR tyrosine kinase inhibitor (TKI) resistance in EGFR mutant lung cancer. METHODS: Ninety-seven specimens from 93 EGFR mutant lung cancer patients (23 tumors with acquired resistance from 20 patients, 45 tumors with intrinsic resistance from 44 patients [nonresponders], 29 sensitive tumors from 29 patients) from 11 institutes in Japan were analyzed. HGF expression, EGFR T790M secondary mutation, and MET amplification were determined by immunohistochemistry, cycleave real-time polymerase chain reaction, and fluorescence in situ hybridization, respectively. RESULTS: High-level HGF expression, EGFR T790M secondary mutation, and MET amplification were detected in 61, 52, and 9% of tumors with acquired resistance, respectively. High-level HGF expression was detected in 29% of tumors with intrinsic resistance (nonresponders), whereas EGFR T790M secondary mutation and MET amplification were detected in 0 and 4%, respectively. HGF expression was significantly higher in tumors with acquired resistance than in sensitive tumors (p < 0.001, Student's t test). Fifty percent of tumors with acquired resistance showed simultaneous HGF expression with EGFR T790M secondary mutation and MET amplification. CONCLUSIONS: High-level HGF expression was detected more frequently than EGFR T790M secondary mutation or MET amplification in tumors with intrinsic and acquired EGFR-TKI resistance in EGFR mutant lung cancer in Japanese patients. These observations provide a rationale for targeting HGF in EGFR-TKI resistance in EGFR mutant lung cancer. PMID- 22052231 TI - Factors associated with the early resumption of sexual activity following medical male circumcision in Nyanza province, Kenya. AB - Research has established that voluntary medical male circumcision (VMMC) reduces HIV acquisition in heterosexual men by approximately 60%; however, engaging in sexual activity before the wound is healed may attenuate this protective effect. This prospective study included VMMC clients who were circumcised in Kenya between November, 2008 and March, 2010, aged >= 18 years, and randomly selected for an interview and genital examination 28-45 days post-VMMC (N = 1,344). At the time of the interview, 91.3% participants were healed. Overall, 30.7% reported engaging in early sexual activity, usually 3-4 weeks post-VMMC. In a multivariable analysis, being married or cohabitating was the strongest predictor of engaging in early sexual activity. Strategies to reduce engaging in sexual activity during the recommended 42-day abstinence period following VMMC should be explored including re-energizing the effort to include female partners in counseling, mass education campaigns, and targeted text messaging programs for VMMC clients. PMID- 22052232 TI - Production of cellulase enzymes during the solid-state fermentation of empty palm fruit bunch fiber. AB - Penicillium verruculosum COKE4E is a fungal strain isolated from bituminous coal. The microorganism cultivated in a minimal medium supplemented with Avicel, carboxymethylcellulose, and oat spelt xylan produced cellulase enzymes as exhibiting carboxymethylcellulase (CMCase), Avicelase, xylanase, and cellobiosidase activities. In this study, the productivity of the extracellular enzymes in the strain was evaluated by using empty palm fruit bunch fiber (EPFBF), a lignocellulosic biomass, as a substrate for solid-state bioconversion. The highest cellulase activities were observed after 6 days of fermentation at pH 6.0 and 30 degrees C. The enzymes were secreted as cellulosomes for the degradation of EPFBF as a sole carbon source. Focused ion beam analysis showed that P. verruculosum COKE4E produced cellulolytic enzymes that were able to effectively biodegrade EPFBF during solid-state fermentation. In this process, 6.5 U of CMCase, 6.8 U of Avicelase, and 8.8 U of xylanase per gram of dry solid EPFBF were produced. These results demonstrate that EPFBF may be a potential raw material in solid-state fermentation for the production of cellulase enzymes to be used for biofuel production. PMID- 22052233 TI - Improving arachidonic acid accumulation in Mortierella alpina through B-group vitamin addition. AB - To improve the arachidonic acid (ARA) accumulation in Mortierella alpina, a mixed B-group vitamin addition strategy was developed. The ARA titer reached up to 10.0 g/L, 1.7-fold of the control. At the same time, the highest specific activities of key enzymes involved in ARA biosynthesis, including malic enzyme, glucose-6 phosphate dehydrogenase and ATP: citrate lyase, were 63.3, 38.6 and 53.7% higher than the control, respectively. The possible vitamin triggered improved ARA accumulation mechanism was thus elucidated that B-group vitamins could function as the cofactors of the key enzymes involved in ARA biosynthesis, or precursors for the formation of NADPH and acetyl-CoA which were crucial for ARA synthesis, and strengthened the related metabolic flux. PMID- 22052234 TI - The prognostic significance of coronary CT angiography. AB - Coronary computed tomography angiography (CTA) is an increasingly utilized, highly accurate noninvasive test for the diagnosis of coronary artery disease. Accumulating data have convincingly demonstrated that the presence, extent, and location of both obstructive and nonobstructive coronary atherosclerosis visualized on coronary CTA conveys powerful prognostic information, incremental to that provided by clinical variables and coronary calcium scoring. Proposed markers of future plaque instability and coronary risk, such as the degree of vessel remodeling and low-attenuation plaque volume, as well as measures of CT myocardial perfusion, may further improve the prognostic value of CTA. Ultimately, studies are needed to assess whether the prognostic information provided by coronary CTA testing results in sustained changes in patient and provider behaviors that cost effectively improve patient outcomes. PMID- 22052235 TI - Oxygen reduction kinetics on graphite cathodes in sediment microbial fuel cells. AB - Sediment microbial fuel cells (SMFCs) have been used as renewable power sources for sensors in fresh and ocean waters. Organic compounds at the anode drive anodic reactions, while oxygen drives cathodic reactions. An understanding of oxygen reduction kinetics and the factors that determine graphite cathode performance is needed to predict cathodic current and potential losses, and eventually to estimate the power production of SMFCs. Our goals were to (1) experimentally quantify the dependence of oxygen reduction kinetics on temperature, electrode potential, and dissolved oxygen concentration for the graphite cathodes of SMFCs and (2) develop a mechanistic model. To accomplish this, we monitored current on polarized cathodes in river and ocean SMFCs. We found that (1) after oxygen reduction is initiated, the current density is linearly dependent on polarization potential for both SMFC types; (2) current density magnitude increases linearly with temperature in river SMFCs but remains constant with temperature in ocean SMFCs; (3) the standard heterogeneous rate constant controls the current density temperature dependence; (4) river and ocean SMFC graphite cathodes have large potential losses, estimated by the model to be 470 mV and 614 mV, respectively; and (5) the electrochemical potential available at the cathode is the primary factor controlling reduction kinetic rates. The mechanistic model based on thermodynamic and electrochemical principles successfully fit and predicted the data. The data, experimental system, and model can be used in future studies to guide SMFC design and deployment, assess SMFC current production, test cathode material performance, and predict cathode contamination. PMID- 22052236 TI - Influence of phospholipid species on membrane fluidity: a meta-analysis for a novel phospholipid fluidity index. AB - Generalized membrane lipid composition determinants of fluidity have been widely investigated, including phospholipid/cholesterol ratio and unsaturation index. Individual phospholipids differ in their physical characteristics, including their interaction with cholesterol and level of unsaturation, emphasizing the importance of examining their individual influence on membrane fluidity. Thus, the purpose of this study was to examine the dominant phospholipids of biological membranes (phosphatidylcholine, PC; phosphatidylethanolamine, PE; sphingomyelin, SM) through a meta-analysis to assess the validity of an inclusive phospholipid fluidity index (PFI = PC/(PE + SM)) as a determinant for membrane fluidity (expressed as polarization of fluorescent probe 1,6 diphenyl-1,3,5-hexatriene) in comparison to previous phospholipid ratios (PC/PE and PC/SM). The results demonstrate that all indices significantly predicted membrane fluidity at 25 degrees C (based on 10-13 data points). In contrast, only PFI approached significance when predicting membrane fluidity at 37 degrees C (P = 0.10 based on five points). As a result, PFI appears to be the only phospholipid index close to significantly predicting membrane fluidity at mammalian physiological temperature. Because this meta-analysis only assessed studies using mammalian membranes, future work should experimentally assess the validity of the PFI utilizing membranes from mammals and a variety of other species and tissues at their respective physiological temperatures. PMID- 22052237 TI - Colchicine modulates oxidative stress in serum and neutrophil of patients with Behcet disease through regulation of Ca2+ release and antioxidant system. AB - Behcet disease (BD) is a chronic, inflammatory, and multisystemic condition with an uncertain pathogenesis. One of the major immunologic findings in BD pathogenesis is increase in activity of neutrophil. An increase in the cytosolic free Ca2+[Ca2+](i) concentration that induces Ca2+ signaling is an important step that participates in the neutrophil activation and reactive oxygen species production that leads to tissue damage in body cells. We aimed to investigate the effects of colchicine on oxidative stress and Ca2+ release in serum and neutrophil of BD patients with active and inactive periods. Twelve Behcet patients (6 active and 6 inactive) and 6 control subject were included in the study. Disease activity was considered by clinical findings. Serum and neutrophil samples were obtained from the patients and control subjects. Neutrophils from patients with active BD were divided into three subgroups and were incubated with colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem, respectively. Erythrocyte sedimentation rate, leucocytes counts, serum C-reactive protein, neutrophil, and serum lipid peroxidation and intracellular Ca2+ release levels were higher in active and inactive groups than in the control group, although their levels were lower in active group than in inactive group. However, neutrophil Ca2+ release levels were decreased in colchicine, verapamil + diltiazem, and colchicine + verapamil + diltiazem groups group compared to active group. Serum glutathione, vitamin A, vitamin E, and beta-carotene concentrations were lower in active and inactive groups than in the control group, although serum vitamin E and beta-carotene concentrations were higher in the inactive group than in the active group. Neutrophil and serum glutathione peroxidase activity within the three groups did not change. In conclusion, we observed the importance of Ca2+ influx into the neutrophils and oxidative stress in the pathogenesis and activation of the patients with BD. Colchicine induced protective effects on oxidative stress by modulating Ca2+ influx in BD patients. PMID- 22052238 TI - Geographic variation in medicare per capita spending. AB - Persistent, widespread variations in Medicare spending across the country are largely and well-documented. In 1996, Medicare per capita spending across the country ranged from $3,000 to $8,500. This synthesis examines the Medicare spending variation, underlying causes, possible solutions, and whether people in higher-spending areas receive better care. Key findings include: Only 10 percent of the Medicare regions had spending within 10 percent of the average. The variation is seen across all Medicare services. Most studies suggest that less than half of the spending variation is accounted for by differences in population characteristics and price. More than half of the spending variation is attributable to differences in use of services. Although research is limited, there is no evidence that areas spending more money have better outcomes or quality of care. Research suggests it is hard to determine why patterns of care and spending vary so much. PMID- 22052239 TI - Mutational analysis of p53 and PTEN in soft tissue sarcoma. AB - p53 and PTEN are the two most frequently mutated tumor suppressors in human cancer. However, literature on the effect of the joint inactivation of tumor suppressor genes in soft tissue sarcoma (STS) is lacking. The purpose of this study was to investigate whether p53 and PTEN mutations play a role in the carcinogenesis of STS, as well as to evaluate their mutual role in STS pathogenesis. We screened mutations of p53 and PTEN in 86 human STSs using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, respectively. p53 mutations were detected in 25.6% (22 out of 86) of STSs: 6 cases of p53 mutations were detected in 46 cases of specific reciprocal translocations in STSs (13.0%), 16 cases were detected in 40 cases of nonspecific reciprocal translocations in STSs (40.0%); the majority of the mutations were point mutations in exon 6-7. Furthermore, PTEN mutations were observed in 2 out of 86 STSs (2.3%). Two out of 86 cases revealed a 130th codon G>A missense mutation in exon 8 of PTEN which resulted in an Arg change to Gln in the PTEN protein structure; and a 334th codon A>T missense mutation in exon 8 of PTEN, which resulted in an Asn change to Lys in the PTEN protein structure. All subjects were examined for p53 exon 5-9 mutations and for PTEN exon 5-9 mutations. However, no tumors contained an alteration of the two genes. The findings indicate that p53 mutations may be involved in the oncogenesis of STS and also suggest that p53 may function as a potential molecular marker for distinguishing between STSs with specific reciprocal translocations and nonspecific reciprocal translocations. Although the existence of PTEN mutations in STS was detected, the PTEN mutation frequency was quite low. We conclude that PTEN may have played a less prognostic role than p53 in the development and malignant transformation of STS in the patients examined. PMID- 22052240 TI - Ocular gene delivery using lentiviral vectors. AB - Substantial advances in our understanding of lentivirus lifecycles and their various constituent proteins have permitted the bioengineering of lentiviral vectors now considered safe enough for clinical trials for both lethal and non lethal diseases. They possess distinct properties that make them particularly suitable for gene delivery in ophthalmic diseases, including high expression, consistent targeting of various post-mitotic ocular cells in vivo and a paucity of associated intraocular inflammation, all contributing to their ability to mediate efficient and stable intraocular gene transfer. In this review, the intraocular tropisms and therapeutic applications of both primate and non-primate lentiviral vectors, and how the unique features of the eye influence these, are discussed. The feasibility of therapeutic targeting using these vectors in animal models of both anterior and posterior ophthalmic disorders has been established, and has, in combination with substantial progress in enhancing lentiviral vector bio-safety over the past two decades, paved the way for the first human ophthalmic clinical trials using lentivirus-based gene transfer vectors. PMID- 22052241 TI - Vector-mediated expression of erythropoietin improves functional outcome after cervical spinal cord contusion injury. AB - We evaluated the therapeutic effect of erythropoietin (EPO) delivered by direct injection of a nonreplicating herpes simplex virus (HSV)-based vector coding for EPO (vEPO) in a model of cervical hemicord contusion at C7. At 1 h after spinal cord injury (SCI), either vEPO or control vector carrying a reporter gene (vC) was injected into the cord above and below the lesion. Animals injected with vEPO showed a statistically significant improvement in the ipsilateral forelimb function, as measured by open-field evaluation of motor performance, forelimb reaching in the cylinder test and misplacement in grid walk. This correlated with preservation of gray matter in the area of the lesion. There was also mild but significant improvement of hindlimb motor function measured by Basso-Beattie Bresnahan score and computerized gait analysis in vEPO compared with control vector-injected animals. Microtubule-associated protein tau, phosphorylated and nonphosphorylated neurofilament protein and the synaptic proteins synaptophysin and PSD-95 were all significantly increased in the spinal cord of vEPO-treated animals compared with control vector-injected animals. These data suggest that gene transfer of EPO after cervical SCI by minimizing the injury size and enhancing tissue sparing preserves large-caliber axons and promotes synaptogenesis. PMID- 22052243 TI - Lumbar lordosis of extinct hominins. AB - The lordotic curvature of the lumbar spine (lumbar lordosis) in humans is a critical component in the ability to achieve upright posture and bipedal gait. Only general estimates of the lordotic angle (LA) of extinct hominins are currently available, most of which are based on the wedging of the vertebral bodies. Recently, a new method for calculating the LA in skeletal material has become available. This method is based on the relationship between the lordotic curvature and the orientation of the inferior articular processes relative to vertebral bodies in the lumbar spines of living primates. Using this relationship, we developed new regression models in order to calculate the LAs in hominins. The new models are based on primate group-means and were used to calculate the LAs in the spines of eight extinct hominins. The results were also compared with the LAs of modern humans and modern nonhuman apes. The lordotic angles of australopithecines (41 degrees +/- 4), H. erectus (45 degrees ) and fossil H. sapiens (54 degrees +/- 14) are similar to those of modern humans (51 degrees +/- 11). This analysis confirms the assumption that human-like lordotic curvature was a morphological change that took place during the acquisition of erect posture and bipedalism as the habitual form of locomotion. Neandertals have smaller lordotic angles (LA = 29 degrees +/- 4) than modern humans, but higher angles than nonhuman apes (22 degrees +/- 3). This suggests possible subtle differences in Neandertal posture and locomotion from that of modern humans. PMID- 22052242 TI - Generating CTLs against the subdominant EBV LMP antigens by transient expression of an A20 inhibitor with EBV LMP proteins in human DCs. AB - Epstein-Barr virus (EBV) infection leads to Hodgkin's disease (HD) in some immunocompetent hosts. The malignant Reed-Sternberg cells of HD only express a limited array of subdominant EBV antigens to evade pre-existing immune responses to EBV. The EBV-encoded latent membrane proteins (LMP1 and LMP2), which are expressed by HD and various EBV-associated malignancies, have been proposed as a potential target for cytotoxic T lymphocyte (CTL)-based therapy. However, the precursor frequency for LMP-specific CTL is generally low in healthy EBV-infected hosts, and immunotherapy based on these antigens is often compromised by the poor immunogenicity and the oncogenic potential. In the present study, we report that transiently expressing an inhibitor of A20, a key negative regulator of inflammatory signaling pathways, together with the LMP antigens (truncated LMP1 and full-length LMP2) greatly enhances maturation and cytokine production of human (h) monocyte-derived dendritic cells (DCs). As a consequence, LMP1/2 expressed, A20-silenced hDCs have an enhanced potency to prime LMP-specific T cell response. When the in vitro primed T cells are adoptively transferred into tumor-xenografted, severe-combined immunodeficient mice, some of the xenografted tumors approach complete regression. Thus, the study may provide an available resource of LMP-specific T cells for T-cell immunotherapy. PMID- 22052245 TI - Medical malpractice - april 2011 update. AB - Although the malpractice crisis--the inability of health care providers to obtain affordable liability insurance--has abated in many states, medical liability costs and pressures remain a concern. In addition, the perceived threat of litigation spurs "defensive medicine"--the practice of ordering services primarily to reduce the physician's liability exposure rather than because they are medically necessary. There is wide consensus that liability pressure undermines efforts to curb overuse of health services, although there is disagreement about the magnitude of its effect. This Update reviews the evidence on the effects of medical malpractice reforms published since the Medical Malpractice: Impact of the Crisis and Effects of State Tort Reforms synthesis was released in 2006. Key findings include: Except for caps on noneconomic damages, there is little evidence that other traditional tort reforms affect medical liability costs or defensive medicine. Average awards are reduced by 20 percent to 30 percent, and premiums in states with caps on noneconomic damages rise 6 percent to 13 percent more slowly than premiums in states without caps. There is evidence that tort reforms-particularly caps on noneconomic damages-reduce health spending, but the size of the reduction is subject to debate. Because of the lack of success of many traditional tort reforms, a number of innovated tort reforms are receiving increased attention. Although they show promise in theory, they have not been widely evaluated so the evidence of their effectiveness is weak. PMID- 22052244 TI - Type 2 diabetes and hepatocellular carcinoma: a case-control study in patients with chronic hepatitis B. AB - Type 2 diabetes has been suggested as an independent risk factor for the development of hepatocellular carcinoma (HCC). However, the role of Type 2 diabetes on the development of HCC in the presence of chronic hepatitis B (CHB) remains inconclusive. We conducted this hospital-based case-control study to evaluate the roles of Type 2 diabetes in HCC development in patients with CHB. From January 2004 to December 2008, a total of 6,275 eligible consecutive patients with chronic hepatitis B virus (HBV) infection were recruited. A total of 1,105 of them were patients with HBV-related HCC and 5,170 patients were CHB but without HCC. We used multivariate logistic regression models to investigate the association between Type 2 diabetes and HCC risk. The prevalence of Type 2 diabetes is higher among HCC patients without cirrhosis than among those with cirrhosis (12.1% vs. 6.7%, p=0.003). Type 2 diabetes was associated with a significantly high risk of HCC in female patients after adjusting for age, family history of HCC, city of residence, hepatitis B e antigen and cirrhosis with an odds ratio (95% confidence interval, CI) of 1.9 (1.1-3.4). Restricted analyses among female patients without cirrhosis indicated that Type 2 diabetes was strongly associated with HCC risk with adjusted odds ratio (95% CI) of 5.6 (2.2 14.1). In conclusion, Type 2 diabetes is independently associated with the increased risk of HCC in female CHB patients. Female CHB patients with Type 2 diabetes are of a high HCC risk population and should be considered for HCC close surveillance program. PMID- 22052246 TI - Assessing guidelines for the discontinuation of prehospital peripheral intravenous catheters. AB - Insertion of prehospital peripheral intravenous (PIV) catheters frequently occurs under suboptimal conditions. Timely replacement of prehospital PIV catheters may minimize the risk of inhospital catheter-related infections. Inconsistent recommendations exist concerning when prehospital PIV catheters should be replaced. The following study assessed compliance with hospital order sets for the discontinuation of prehospital PIV catheters in trauma patients and their associated complications. Results revealed 33.62% compliance with the trauma order set and 66.38% compliance with the hospital order set. Less than 1% of patients exhibited an associated complication. Guidelines for replacement of prehospital PIV catheters should focus less on time since insertion and more on patient factors. PMID- 22052247 TI - Calcium imaging of neuronal activity in the most rostral parafacial respiratory group of the newborn rat. AB - The parafacial respiratory group (pFRG) is thought to be involved in respiratory rhythm generation in neonates. This subgroup expresses the transcription factor, Phox2b, and contains intrinsically CO(2) sensitive neurons. Calcium imaging has been widely used for analysis of neuronal activity at the cellular and network level. In the present study, we applied calcium imaging to analyze neuronal activity of the most-rostral pFRG in an in vitro brainstem-spinal cord preparation from neonatal rats. We detected strong pre-inspiratory neuron activity in the most rostral pFRG, suggesting that significant numbers of pre inspiratory neurons are localized in the ventrolateral medulla near the rostral end of the medulla. We show that usage of calcium imaging would be very useful for analysis of neuronal activity over different time scales, and discuss the advantages and disadvantages of this method. PMID- 22052248 TI - Spiritist psychiatric hospitals in Brazil: integration of conventional psychiatric treatment and spiritual complementary therapy. AB - In Brazil, during the XX century, dozens of Spiritist psychiatric hospitals emerged seeking to integrate conventional medical treatment with complementary spiritual therapy. This combined inpatient treatment is largely found in Brazil, where many psychiatric hospitals stem from the Spiritist movement. The present report describes the use of these spiritual practices, their operating structure, health professionals involved, modalities of care, and institutional difficulties in integrating spiritual practices with conventional treatment in six leading Brazilian Spiritist psychiatric hospitals. These hospitals combine conventional psychiatric treatment with voluntary-based spiritual approaches such as laying on of hands ("fluidotherapy"), lectures regarding spiritual and ethical issues, intercessory prayer, spirit release therapy ("disobsession") and "fraternal dialogue". The non-indoctrination and optional nature of these spiritual complementary therapies seem to increase acceptance among patients and their family members. In conclusion, the Spiritist psychiatric hospitals in Brazil have, for more than half a century, provided an integrative approach in the treatment of psychiatric disorders, associating conventional and spiritual treatments, more specifically Spiritist therapy. The lack of standardized treatment protocols and scientific studies remain a barrier to assessing the impact of this integrative approach on patients' mental health, quality of life, adherence, and perceived quality of treatment. PMID- 22052249 TI - Macroglossia and generalized edema not due to hypothyroidism. AB - We present a 69-year-old male patient with the macroglossia, dysphagia and generalized edema. He was seen previously by other physicians and diagnosed as hypothyroidism. With thyroid stimulating hormone in normal range, tongue biopsy revealed primary systemic amyloidosis. Amyloidosis is the most common cause of macroglossia. Primary systemic amyloidosis should be suspected when laboratory does not support hypothyroidism especially if the enlarged tongue is firm and additional findings are present. PMID- 22052250 TI - Probing Lewis acidity of Y(BH4)3 via its reactions with MBH4 (M = Li, Na, K, NMe4). AB - High-energy milling of Y(BH(4))(3) (containing LiCl as a by-product, which has not been removed) with MBH(4) (M = Li, Na, K, (CH(3))(4)N) leads to the first two examples of quasi-ternary yttrium borohydrides: KY(BH(4))(4) and (CH(3))(4)NY(BH(4))(4), while no chemical reaction is observed for LiBH(4) and NaBH(4). KY(BH(4))(4) is isostructural to NaSc(BH(4))(4) (Cmcm, a = 8.5157(4) A, b = 12.4979(6) A, c = 9.6368(5) A, V = 1025.62(9) A(3), Z = 4), while (CH(3))(4)NY(BH(4))(4) crystallises in primitive orthorhombic cell, similarly to KSc(BH(4))(4) (Pnma, a = 15.0290(10) A, b = 8.5164(6) A, c = 12.0811(7) A, V = 1546.29(17) A(3), Z = 4). The thermal decomposition of hydrogen-rich KY(BH(4))(4) (8.6 wt.% H) involves the formation of an unidentified intermediate at 200 degrees C and recovery of KBH(4) at higher temperatures; at 410 degrees C, KCl and YH(2) are observed. The thermal decomposition of (CH(3))(4)NY(BH(4))(4) occurs via two partly overlapping endothermic steps with concomitant emission of H(2) and organic compounds. Heating of a NaBH(4)/Y(BH(4))(3) mixture above 165 degrees C results in a mixed-cation mixed-anion borohydride, NaY(BH(4))(2)Cl(2), but not NaY(BH(4))(4). The reduced reactivity of Y(BH(4))(3) towards borohydride Lewis bases when compared to hypothetical scandium borohydride can be explained by the lower Lewis acidity of Y(BH(4))(3) than Sc(BH(4))(3). PMID- 22052251 TI - How will employers respond to coverage reforms. AB - Any change in the health insurance market could prompt a reaction by employers in what kind and at what cost they offer coverage. This policy brief examines the research on employer decision-making. Key findings include: Firms are most likely to offer plans that respond to the preferences of their most valuable, hard-to retain workers. Firms are more likely to offer health insurance if they employ high-wage workers; if they are unionized; or if they are in the manufacturing or public sectors. While theory suggests that employers will shift the cost of premiums to employees in the form of lower wages, this is not the case in practice. There are serious gaps in research, including: an absence of detailed data about individuals; little information about earnings distribution; ages and other characteristics within firms of different sizes; and little study of employer behavior. PMID- 22052252 TI - Ephemeral association between gene CG5762 and hybrid male sterility in Drosophila sibling species. AB - Interspecies divergence in regulatory pathways may result in hybrid male sterility (HMS) when dominance and epistatic interactions between alleles that are functional within one genome are disrupted in hybrid genomes. The identification of genes contributing to HMS and other hybrid dysfunctions is essential for understanding the origin of new species (speciation). Previously, we identified a panel of male-specific loci misexpressed in sterile male hybrids of Drosophila simulans and D. mauritiana relative to parental species. In the current work, we attempt to dissect the genetic associations between HMS and one of the genes, CG5762, a Drosophila-unique locus characterized by rapid sequence divergence within the genus, presumably driven by positive natural selection. CG5762 is underexpressed in sterile backcross males compared with their fertile brothers. In CG5762 heterozygotes, the D. mauritiana allele is consistently overexpressed on both the D. simulans and D. mauritiana backcross genomic background, suggesting a cis-acting regulation factor. There is a significant association between heterozygosity and HMS in hybrid males from early but not later backcross generations. Microsatellite markers spanning CG5762 fail to associate with HMS. These observations lead to a conclusion that CG5762 is not a causative factor of HMS. Although genetic linkage between CG5762 and a neighboring causative introgression cannot be ruled out, it seems that the pattern is most consistent with CG5762 participating in epistatic interactions that are disrupted in flies with HMS. PMID- 22052253 TI - Enhanced antitumor activity of epirubicin combined with cerulenin in osteosarcoma. AB - Osteosarcoma (OS) is the most common primary malignant neoplasm in children and adolescents. Epirubicin is one of the chemotherapeutic agents currently used for the treatment of OS; however, the efficacy of chemotherapy is hampered by the acquired drug resistance of OS. Cerulenin, an inhibitor of fatty acid synthase, has been defined as a candidate tumor suppressor. In this study, we explored the combined effect of cerulenin plus the chemotherapy drug, epirubicin, on human OS U2-OS cells in vitro and in vivo. We demonstrated that cerulenin plus epirubicin induced synergistic growth inhibition and enhanced apoptosis in U2-OS cells. We also demonstrated that cerulenin plus epirubicin synergistically suppressed tumor growth in subcutaneously xenografted U2-OS cells in athymic nude mice. Our results indicate that cerulenin enhances the anti-OS effects of epirubicin in vivo and in vitro. PMID- 22052254 TI - Quality of life and health status before and after ileal pouch-anal anastomosis for ulcerative colitis. AB - BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is considered the surgical treatment of choice for patients with ulcerative colitis. Quality of life (QoL) and health status are the most important patient-related outcomes. Studies investigating QoL are often cross-sectional and focus on health status. This longitudinal study evaluated QoL and health status after IPAA for ulcerative colitis and compared these with reference data from a healthy population. METHODS: Patients with ulcerative colitis who underwent a pouch operation between 2003 and 2008 completed validated questionnaires for QoL and health status. Questionnaires were completed before pouch surgery, and 6, 12, 24 and 36 months after operation. The effect of IPAA on QoL and health status was analysed, and data were compared with reference values from the healthy Dutch population. RESULTS: Data were obtained for 30 of the 32 patients. Six months after IPAA, QoL was at least comparable with that of the reference population in four of six domains. Twelve months after IPAA, overall QoL had improved, supported by findings in three QoL domains. Six months after IPAA, health status was comparable to that of the reference population in three of eight dimensions, and after 3 years it was at least comparable in five dimensions. CONCLUSION: QoL and health status increased after IPAA and reached levels comparable with those of the healthy reference population in a majority of domains and dimensions. QoL was restored first after IPAA, followed by health status. PMID- 22052256 TI - Quercetin production from rutin by a thermostable beta-rutinosidase from Pyrococcus furiosus. AB - Pyrococcus furiosus beta-glucosidase converted rutin to quercetin and rutinose disaccharide with a ratio of 1:1, with no glucose, L-rhamnose, and isoquercitrin, indicating that the enzyme is a beta-rutinosidase. The specific activity for flavonoid glycosides followed the order of isoquercitrin > quercitrin > rutin. The conversion of rutin to quercetin was optimal at pH 5.0 and 95 degrees C in the presence of 0.5% dimethyl sulfoxide with a half-life of 101 h, a k(cat) of 1.6 min(-1), and a K(m) of 0.3 mM. Under the improved conditions, the enzyme produced 6.5 mM quercetin from 10 mM rutin after 150 min, with a molar yield of 65% and a productivity of 2.6 mM/h. This productivity is the highest reported thus far among enzymatic transformations. PMID- 22052255 TI - Depletion of tissue factor suppresses hepatic metastasis and tumor growth in colorectal cancer via the downregulation of MMPs and the induction of autophagy and apoptosis. AB - Tissue factor (TF) is a significant risk factor for hepatic metastasis in patients with colorectal cancer (CRC). However, the mechanism by which TF promotes hepatic metastasis in CRC remains elusive. In this study, we first confirmed that TF expression was significantly correlated with lymph node metastasis, hepatic metastasis and TNM staging in clinical CRC samples, and found that TF expression in colon cancer cell lines was correlated with the invasion ability. Next, by employing TF-overexpressing LOVO cell line as a model we demonstrated that lentivirus mediated knockdown of TF suppressed the migration and invasion of LOVO cells in vitro, and hepatic metastasis of colorectal cancer in nude mice orthotopic model. Mechanistically, we found that TF knockdown decreases colony formation ability and induced autophagy and apoptosis of LOVO cells, and this was at least partly mediated by the activation of unfolded protein response/PERK signaling. In conclusion, our data provide new insight into hepatic metastasis of CRC. Agents targeting TF should be developed as adjuvant therapeutics for CRC metastasis. PMID- 22052257 TI - Construction of engineered fructosyl peptidyl oxidase for enzyme sensor applications under normal atmospheric conditions. AB - Current enzymatic methods for the analysis of glycated proteins use flavoenzymes that catalyze the oxidative deglycation of fructosyl peptides, designated as fructosyl peptidyl oxidases (FPOXs). However, as FPOXs are oxidases, the signals derived from electron mediator-type electrochemical monitoring based on them are affected by dissolved O(2). Improvement of dye-mediated dehydrogenase activity of FPOXs and its application to enzyme electrode construction were therefore undertaken. Saturation mutagenesis study on Asn56 of FPOX from Phaeosphaeria nodorum, produced mutants with marked decreases in the catalytic ability to employ O(2) as the electron acceptor, while showing higher dye-mediated dehydrogenase activity employing artificial electron acceptors than the parental enzyme. Thus constructed virtually fructosyl peptide dehydrogenase, Asn56Ala, was then applied to produce an enzyme electrode for the measurement of fructosyl (alpha) N-valyl-histidine (f-(alpha)Val-His), the protease-digested product of HbA1c. The enzyme electrode could measure f-(alpha)Val-His in the physiological target range in air. PMID- 22052258 TI - High-level expression of the Penicillium notatum glucose oxidase gene in Pichia pastoris using codon optimization. AB - The glucose oxidase (GOD) gene from Penicillium notatum was expressed in Pichia pastoris. The 1,815 bp gene, god-w, encodes 604 amino acids. Recombinant GOD-w had optimal activity at 35-40 degrees C and pH 6.2 and was stable, from pH 3 to 7 maintaining >75% maximum activity after incubation at 50 degrees C for 1 h. GOD-w worked as well as commercial GODs to improve bread making. To achieve high-level expression of recombinant GOD in P. pastoris, 272 nucleotides involving 228 residues were mutated, consistent with the codon bias of P. pastoris. The optimized recombinant GOD-m yielded 615 U ml(-1) (2.5 g protein l(-1)) in a 3 l fermentor--410% higher than GOD-w (148 U ml(-1)), and thus is a low-cost alternative for the bread baking industry. PMID- 22052259 TI - MTHFR polymorphisms, folate intake and carcinogen DNA adducts in the lung. AB - The methylenetetrahydrofolate reductase (MTHFR) genes and folate in one-carbon metabolism are essential for DNA methylation and synthesis. However, their role in carcinogen DNA damage in target lung tissue, a dosimeter for cancer risk, is not known. Our study aimed to investigate the association between genetic and nutritional one-carbon metabolism factors and DNA adducts in target lung. Data on 135 lung cancer cases from the Massachusetts General Hospital were studied. Genotyping was completed for MTHFR C677T (rs1801133) and A1298C (rs1801131). Information on dietary intake for one-carbon related micronutrients, folate and other B vitamin was derived from a validated food frequency questionnaire. DNA adducts in lung were measured by (32) P-postlabeling. After adjusting for potential confounders, DNA adduct levels in lung significantly increased by 69.2% [95% confidence interval (CI), 5.5% to 171.5%] for the MTHFR 1298AC+CC genotype. The high risk group, combining the A1298C (AC+CC) plus C677T (CT+TT) genotypes, had significantly enhanced levels of lung adducts by 210.7% (95% CI, 21.4% to 695.2%) in contrast to the A1298C (AA) plus C677T (CC) genotypes. Elevation of DNA adduct was pronounced-111.3% (95% CI, -3.0 to 360.5%) among 1298AC+CC patients, who consumed the lowest level of folate intake as compared to 1298AA individuals with highest tertile of intake. These results indicate that DNA adducts levels are influenced by MTHFR polymorphisms and low folate consumption, suggesting an important role of genetic and nutritional factors in protecting DNA damage from lung carcinogen in at-risk populations. PMID- 22052260 TI - The new face of fillers: why evidence and experience both count. PMID- 22052261 TI - Commentary: rheological evaluation of the physical properties of hyaluronic acid dermal fillers. PMID- 22052262 TI - Doxycycline vs. minocycline for the management of acne. PMID- 22052264 TI - The Frontalis Activity Measurement Standard: a novel contralateral method for assessing botulinum neurotoxin type-A activity. AB - BACKGROUND: There are conflicting data regarding the specific attributes of botulinum neurotoxin type-A (BoNTA) products including onset of action, duration and spread because accurate, objective methods for assessing their clinical activity are lacking. OBJECTIVE: To refine definitions for BoNTA activity utilizing the frontalis muscle and describe the Frontalis Activity Measurement Standard (FMS), an objective method for measuring changes in frontalis muscle activity as a metric for assessing BoNTA pharmacodynamics. METHODS: As part of a study to assess BoNTA activity, 20 subjects with severe frontalis lines at maximum elevation were injected with two BoNTA products at five points on contralateral sides of the frontalis. Changes in maximum baseline frontalis elevation were measured by a blinded investigator using the previously-validated Frontalis Rating Scale (FRS) and the FMS. Frontalis activity endpoints were redefined to include Initial, Full and Complete Onsets of action and Partial, Full and Complete efficacy. RESULTS: Differences in the onset of effect of the BoNTA products were detected with both the FRS and FMS; however, the FMS detected changes in frontalis activity earlier than the FRS. A significant correlation between the FRS and FMS was documented. CONCLUSION: The frontalis muscle activity allows for enhanced assessment of BoNTA activity and attributes. The FMS appears to be a sensitive and objective tool for measuring pharmacodynamic parameters of BoNTA. Refining definitions of BoNTA activity provides a more accurate means for describing the clinical effects of BoNTA. PMID- 22052265 TI - Rheological evaluation of the physical properties of hyaluronic acid dermal fillers. AB - BACKGROUND: Hyaluronic acid (HA) gels are commonly injected into the skin to lift rhytides and to improve facial appearance. The different processes used in their manufacture and formulation yield products with unique physical characteristics that play an important role in predicting their clinical performance. OBJECTIVE: The following rheologic evaluation was performed to objectively measure the physical characteristics of HA dermal filler products derived from similar bacterial sources and containing the same butanediol diglycidyl ether cross linker, but formulated using different manufacturing techniques. The objective of this study was to evaluate the physical characteristics of two distinct families of HA products, thereby providing clinicians with a greater understanding of these products' attributes and the ability to optimize their use in the treatment of patients seeking facial rejuvenation. MATERIALS AND METHODS: The physical properties of commercially-available dermal fillers containing HA were evaluated using rheologic testing methods under clinically-relevant conditions. Additionally, light microscopy was used to assess the particulate nature of each product. RESULTS: The gels tested demonstrated a broad range of elasticity, firmness and viscosity. Light microscopy confirmed the particulate nature of each product and revealed HA particles of varying size and distribution. CONCLUSION: This rheologic evaluation demonstrates that differences exist among the HA products tested including gel elasticity, viscosity, and the range and distribution of gel particle sizes. Understanding the distinct physical characteristics of different HA dermal fillers and how these characteristics may predict their clinical behavior can assist clinicians in achieving the desired results in patients seeking facial rejuvenation. PMID- 22052266 TI - Safety and effectiveness of small and large gel-particle hyaluronic acid in the correction of perioral wrinkles. AB - BACKGROUND: FDA-approved for the correction of moderate-to-severe facial wrinkles and folds, small gel-particle hyaluronic acid (SGP-HA, Restylane, Medicis Aesthetics, Inc., Scottsdale, AZ) and large gel-particle hyaluronic acid (LGP-HA, Perlane, Medicis Aesthetics, Inc., Scottsdale, AZ) were studied to evaluate their safety for the correction of oral commissures, marionette lines, upper perioral rhytides and nasolabial folds (NLFs). OBJECTIVES: The primary objective of this study was to investigate the safety of SGP-HA and LGP-HA in treating facial wrinkles and folds around the mouth; the secondary objective was to evaluate the effectiveness of these products. METHODS: This open-label, 4-week study at two US centers evaluated SGP-HA and LGP-HA in patients who intended to undergo intradermal injection for correction of of perioral wrinkles and folds. At screening, a 5-grade Wrinkle Severity Rating Scale (WSRS) was used to evaluate the baseline appearance of bilateral NLFs, and a 6-grade Wrinkle Severity (WS) scale was used to evaluate the appearance of bilateral oral commissures, marionette lines and upper perioral rhytides. To qualify, each patient must have had moderate-to-severe wrinkles at one pair of marionette lines and upper perioral rhytides. Each wrinkle was treated to optimal correction with either SGP HA or LGP-HA at the discretion of the treating investigator. All reported local and systemic adverse events (AEs) were recorded. At two weeks after treatment or touch-up, the treating investigator and the patient assessed appearance using the Global Aesthetic Improvement Scale (GAIS). RESULTS: Twenty patients with a mean age of 59.6 years (range 49 to 65 years) were treated with an average of 5.58 plus minus 1.15 mL of HA for the entire perioral area. Treatment areas included NLFs, marionette lines, oral commissures and perioral rhytides. Eighteen of 20 patients received both SGP-HA and LGP-HA. Product was injected into the mid or deep dermis using primarily linear threading and multiple punctate pools. Patients experienced a total of 66 treatment-emergent AEs (TEAEs); each patient experienced at least one TEAE. The reported events in decreasing order of occurrence were bruising, tenderness, swelling, redness, headache and discomfort. Bruising was more common in the NLFs and marionette lines than in the oral commissures and perioral rhytides. Tenderness occurred more often in the perioral rhytides than in the other areas. The maximum intensity of all TEAEs was considered mild. Most TEAEs resolved within seven days, with an average duration of four days. No serious TEAEs occurred during the study. One hundred percent of GAIS evaluations by both investigators and patients indicated improvement, regardless of filler used or area treated. CONCLUSION: Both SGP-HA and LGP-HA were found to be safe and effective for the correction of perioral wrinkles and folds, with few differences among treatment areas Both investigator and patient GAIS evaluations indicated aesthetic improvement after SGP-HA and LGP-HA treatment in the perioral area. PMID- 22052267 TI - Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. AB - BACKGROUND: Due to its strong water-binding potential, hyaluronic acid (HA) is a well-known active ingredient for cosmetic applications. Native HA is proposed to help the skin to retain and maintain elasticity, turgor and moisture. OBJECTIVE: To observe the efficacy of topical application of 0.1% hyaluronan formulations of different molecular weights (MW) (50, 130, 300, 800 and 2000 kDa, respectively) in the periocular area as anti-wrinkle treatment. MATERIAL AND METHODS: Seventy six female subjects between 30 and 60 years of age with clinical signs of periocular wrinkles applied one of the formulations twice-daily to the area of interest in a randomized fashion for 60 days. Around the other eye, a vehicle control cream was applied. Measurements of skin hydration and skin elasticity were performed before treatment, 30 and 60 days thereafter. At similar time points negative replicas were taken and evaluated by semi-automated morphometry. RESULTS: All HA-based creams utilized in this study demonstrated a significant improvement in skin hydration and overall elasticity values (R2) when compared to placebo. Measurements of wrinkle depth using mean roughness (Ra) and maximum roughness (Rz) values revealed significant improvement in the 130 and the 50 kDa HA group after 60 days of treatment compared to placebo-treated area. CONCLUSION: Topical application of all 0.1% HA formulations used in this study led to significant improvement in skin hydration and elasticity. Application of low molecular-weight (LMW) HA was associated with significant reduction of wrinkle depth, which may be due to better penetration abilities of LMW HA. PMID- 22052268 TI - The evolution of injectable poly-L-lactic acid from the correction of HIV-related facial lipoatrophy to aging-related facial contour deficiencies. AB - Loss of facial volume due to skeletal resorption and facial fat redistribution is considered a primary cause for increased skin folding and sagging associated with aging. The objective of this review is to examine how use of injectable poly-L lactic acid (PLLA) for correction of human immunodeficiency virus (HIV) associated facial lipoatrophy supports wider use in treating aging-related facial changes given its approval for aesthetic use. A literature review of studies evaluating injectable PLLA for the treatment of HIV-associated or aging-related contour deficiencies was conducted via MEDLINE, supplemented by the author's clinical experience. In clinical trials of HIV-related facial lipoatrophy, injectable PLLA increased dermal thickness for up to 96 weeks. Another study showed significant improvements in aging-related nasolabial fold wrinkles that lasted up to 25 months. Understanding differences in the use of injectable PLLA between patients with HIV and those with aging-related facial changes will help physicians optimize patient treatment. PMID- 22052269 TI - Management of impending necrosis associated with soft tissue filler injections. AB - BACKGROUND: As the number of soft tissue filler injections increases, the number of adverse events associated with injection may rise. Impending necrosis represents a serious complication that, if not treated correctly and timely, may have grave consequences. OBJECTIVE: We describe a protocol utilizing hyaluronidase, nitroglycerin paste, aspirin, antacid and a topical oxygen therapy that may be used to treat impending necrosis subsequent to injection with soft tissue fillers. CONCLUSION: We have successfully treated nine post-filler injection adverse events involving impending necrosis or necrosis following both hyaluronic acid and calcium hydroxylapatite injections using our protocol. PMID- 22052270 TI - Same-patient prospective comparison of Botox versus Dysport for the treatment of primary axillary hyperhidrosis and review of literature. AB - BACKGROUND: Botulinum toxin (BTX) is an effective, FDA-approved treatment for primary axillary hyperhidrosis. In this prospective study, two non-bioequivalent toxins: Botox (Allergan, Irvine, CA, USA) and Dysport (Ipsen Ltd., Slough, Berkshire, UK) were compared for the treatment of primary axillary hyperhidrosis. OBJECTIVE: The objective was to compare the injection site pain, efficacy, safety and tolerability of Botox versus Dysport in the treatment of primary axillary hyperhidrosis using a conversion factor of 1:3, respectively. METHODS: A patient with primary axillary hyperhidrosis was treated with 100 units of Botox into the right axilla and 300 units of Dysport into the left axilla. Patient was blinded as to which axilla received treatment and with which of the two toxins. Pain at the injection site of these two toxins was evaluated. The patient was subsequently followed for the next 10 months to evaluate the difference in these two toxins in regards to side effects, time to the onset of reduction of sweating and the duration of action of these two toxins. RESULTS: Significant difference was observed in the onset of action of these two toxins, with dramatic reduction in sweating being observed after one week of injection with Botox and after two weeks of injection with Dysport. At the two-week time point, similar success in eliminating sweating was reported in both axilla. The duration of benefits also differed between the two toxins, with elimination of sweating in the Dysport treated axilla lasting six months and, in the Botox-treated axilla, nine months. No other differences were observed between these two toxins. CONCLUSIONS: Both Botox and Dysport led to a similar perceived reduction of sweating in the treatment of primary axillary hyperhidrosis when a conversion factor of 1:3 was used. However, Botox treatment resulted in a quicker onset of action and longer duration of benefits. PMID- 22052271 TI - Drug-induced urticaria: causes and clinical courses. AB - The authors retrospectively reviewed medical records of patients who were diagnosed as having drug-induced urticaria at Siriraj Hospital of Mahidol University (Bangkok, Thailand) between October 2004 and April 2007. One hundred and forty-seven drugs were presumed as causing acute urticaria. Females were affected more commonly than males. The most frequent drug groups were antibiotics, followed by non-steroidal anti-inflammatory drugs (NSAIDs). The most common culprit drugs were ceftriaxone, cephalexin, amoxicillin and diclofenac, respectively. The median duration of onset and of clinical remission were 18 hours and 24 hours, respectively. Antibiotics were the most frequent causes of drug-induced urticaria, of which cephalosporins were the most common causative drugs. Oral NSAIDs significantly had the shortest median onset of urticaria. After discontinuing the culprit drugs, the reactions usually disappeared within a few days. PMID- 22052272 TI - A comparative study of the safety and efficacy of 75% mulberry (Morus alba) extract oil versus placebo as a topical treatment for melasma: a randomized, single-blind, placebo-controlled trial. AB - BACKGROUND: Melasma is an aesthetically undesirable skin condition which remains difficult to treat. Mulberry is a whitening agent with antioxidant properties. OBJECTIVE: To evaluate the safety and efficacy of 75% mulberry extract oil as a treatment for melasma versus placebo. PATIENTS AND METHODS: 50 patients were recruited and randomly assigned into two groups, with 25 treated with 75% mulberry extract oil and the other 25 treated with placebo. All patients had a negative repeat open application test (ROAT) to both mulberry extract and placebo. Patients were followed up regularly at four-week intervals for a total of eight weeks. The severity of the melasma was assessed using the melasma area and severity score (MASI), Mexameter reading, melasma quality of life score (MelasQOL) and any adverse events noted. RESULTS: The mean MASI score significantly improved from 4.076 (+/- 0.24) at baseline to 2.884 (+/- 0.25) at week 8 for the 75% mulberry extract oil group while the placebo group showed an improvement of a lesser magnitude. Mexameter readings for the mulberry group showed a significant drop from 355.56 (+/- 59.51) at baseline to 312.52 (+/- 57.03) at week 8 compared to the placebo group, whose Mexameter readings deteriorated from 368.24 (+/- 46.62) at baseline to 372.12 (+/- 44.47) at week 8. The MelasQOL score also improved tremendously for the 75% mulberry extract oil group, falling from 58.84 (SD: +/- 3.18) at baseline to 44.16 (SD: +/- 4.29) at week 8, unlike the placebo group that showed a less dramatic improvement from 57.44 (SD: +/- 4.66) at baseline to 54.28 (SD: +/- 4.79) at week 8. With regards to the adverse events, only mild itching was reported in four patients from the 75% mulberry extract oil group while there were 12 cases of either itching or erythema reported from the placebo group. PMID- 22052273 TI - Treatment of vitiligo with a melanocyte-keratinocyte cell suspension versus dermabrasion only: a pilot study with a 12-month follow up. AB - BACKGROUND: Dermabrasion is a surgical procedure that has been used for repigmentation; however, autologous transplantation of uncultured melanocytes in a suspension combined with the use of adjunct treatment provides better results. PURPOSE: To evaluate the clinical effectiveness of dermoabrasion (DA) and melanocyte-keratinocyte cell suspension transplantation (DA+MKT) vs. dermabrasion with no adjunct treatment. MATERIALS AND METHODS: We selected 11 patients (six women and five men) with stable vitiligo. From these, two achromic maculae of similar size were selected. One macule was treated with DA+MKT and the other with DA only. The main parameter of treatment efficacy was the percentage of repigmentation in the area treated, three and 12 months after implantation. RESULTS: In seven of the 11 patients, slightly better pigmentation occurred with DA+MKT. Two of these patients had a repigmentation greater than 50 percent and in two other patients, the result was similar for both techniques, although slightly better with MKT. Two more patients showed less than 20 percent repigmentation, but only in the area treated with DA+MKT. One patient showed pigmentation initially after DA+MKT only, and subsequent depigmentation. CONCLUSION: DA+MKT produced slightly better repigmentation than DA only when given without adjunct treatment in a 12-month follow-up period. PMID- 22052274 TI - Nanotechnology and dermatology education in the United States: data from a pilot survey. AB - BACKGROUND: Nanotechnology is a rapidly growing discipline with important implications for consumers, patients, physicians and investigators. In an era when nanotechnology is being both incorporated into educational requirements for medical fields such as radiology and oncology and vigorously pursued and developed by cosmeceutical companies, dermatology is falling behind. A survey was conducted to ascertain knowledge, attitudes and perception of nanotechnology in dermatology teaching programs. METHODS: To ascertain baseline knowledge, attitudes and preceptions regarding nanotechnology among dermatology trainees, dermatology investigators and dermatology faculty in US academic medical centers, an online survey was sent out to random members of the dermatology community and data analyzed (100 participants, 23% response rate). Participants responded to a questionnaire on a five-point scale ranging from strongly disagree, disagree, uncertain, agree, to strongly agree. Due to the low response rate, strongly disagree/disagree and strongly agree/agree values were combined and compared to uncertain responses. RESULTS: Approximately equal numbers of faculty vs. chief residents responded to the survery (52% vs. 47.75%, respectively). The majority of respondents had not previously attended any educational activity on nanotechnology (69.57%). The majority of participants agreed that more education on nanotechnology for dermatologists is needed (78.26% agreed vs. 21.74% uncertain) and that it should be incorporated into the residency training curriculum (60.87% agree vs. 13.04% disagree). Participants mostly agreed that nanotechnology research can contribute to better fundamental understanding of skin disease (78.26%), to advances in the diagnosis of skin disease (73.91%) and to therapies (78.26%). Participants mostly agreed that more research is needed (82.60%) and that this research should be funded (78.26%). Not surprisingly, respondents were uncertain with respect to issues of nanotechnology safety both in the pharmaceutical realm (60.87%) and cosmeceutical realm (69.57%). Furthermore, the overwhelming majority responded that research is also needed to evaluate nanomaterial safety (86.96%). LIMITATIONS: Both the populations size and response rate were low, possibly affecting the power and significance of the results in this study. CONCLUSION: The survey results indicate a significant gap in dermatology training. Participants indicated a need for more training and education in the area of nanotechnology, and called for more research to evaluate the potential pitfalls associated with nanomaterials as well and to seek new advances in diagnostic and therapeutic modalities. PMID- 22052275 TI - A novel treatment for ulcerative calcinosis cutis. AB - BACKGROUND: Calcinosis cutis is a term used to describe a group of disorders which result in calcium deposits in the skin. These disorders can be separated based on etiology. OBJECTIVE AND METHODS: Sodium thiosulfate has been used to systemically treat calciphylaxis with little to no adverse effects. We report two cases of ulcerative calcinosis cutis which were refractory to multiple topical treatments and did not improve with correction of underlying electrolyte abnormalities. RESULTS: Both cases showed an excellent response to topical 25% sodium thiosulfate compounded in zinc oxide. LIMITATIONS: We are limited by a small sample size (n=2) in this case series. CONCLUSIONS: We recommend topical sodium thiosulfate 25% as an alternative treatment for dystrophic calcinosis cutis. PMID- 22052276 TI - A randomized, blinded, bilateral intraindividual, vehicle-controlled trial of the use of photodynamic therapy with 5-aminolevulinic acid and blue light for the treatment of actinic keratoses of the upper extremities. AB - BACKGROUND/OBJECTIVE: Actinic keratoses (AKs) on the upper extremities are difficult to treat. This study compares the efficacy and tolerability of photodynamic therapy (PDT) using 20% 5-aminolevulinic acid solution (ALA) and blue light versus ALA vehicle and blue light for the treatment of AKs of the dorsal hand and forearm. METHODS: Subjects were treated twice at an eight-week interval by ALA with blue light on one hand and forearm and with ALA vehicle and blue light on the contralateral hand and forearm. ALA incubation time was two hours under occlusion. Efficacy and tolerability were compared. RESULTS: The mean lesion count reductions (58.4 +/- 22.2% and 24.8 +/- s20.6% four weeks after the second treatment for the ALA and vehicle-treated sides, respectively) differed significantly (P=0.0004). Eleven of 15 subjects (73%) in the ALA-treated side achieved at least 50 percent reduction in lesion count compared to only two subjects (13%) in the vehicle-treated side four weeks after the second treatment. The difference was significant (P=0.0143). Photodamage grade reduction was also significant (P=0.0309) after the second treatment. Subject satisfaction was moderate to very satisfied (86.7%) on the ALA-treated side. Transient adverse events were significantly greater on the ALA-treated side for erythema (P=0.0011), edema (P=0.0199) and stinging and burning (P=0.0016) 48 hours after the first treatment. CONCLUSIONS: Two sessions of PDT using ALA with blue light is a moderately effective, well-tolerated treatment of actinic keratoses of the dorsal hand and forearm. PMID- 22052277 TI - Severe cutaneous reaction to photodynamic therapy with blue light. AB - Photodynamic therapy (PDT) has been considered a safe and efficacious treatment for actinic keratoses (AKs) of the scalp and face. The procedure involves exposing a patient to a blue light source 1-4 hours after application of photosensitizing aminolevulinic acid (ALA) at a dose of 10 J/cm2 for up to 1000 seconds.(1,2) We suggest that amount of exposure time and area of exposure should be stratified according to baseline photodamage. PMID- 22052278 TI - Treatment of peristomal pyoderma gangrenosum with topical crushed dapsone. AB - A 27-year-old male with a history of Crohn's disease was treated for chronic pyoderma gangrenosum at his stoma site. Treatment with topical application of crushed dapsone resulted in improvement of his pyoderma gangrenosum. Crushed dapsone may be an efficacious treatment with minimal systemic side effects. This appears to be the first case of pyoderma gangrenosum treated with crushed dapsone. PMID- 22052279 TI - Pigmentary changes in a patient treated with imatinib. AB - Imatinib mesylate (STI 571; Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) is an orally available tyrosine kinase inhibitor that targets a constitutively activated BCR-ABL tyrosine kinase with additional inhibitory effects on platelet derived growth factor (PDGF) receptors alpha and beta, and KIT. It has revolutionized the treatment of adult and pediatric patients with Philadelphia chromosome positive chronic myelogenous leukemia (CML) and is also FDA-approved for KIT-positive advanced gastrointestinal tumor (GIST) and dermatofibrosarcoma protuberans. A wide spectrum of dermatologic toxicities has been associated with this agent, among which a maculopapular rash is the most common event. In addition, a variety of pigmentary abnormalities of the skin and mucosal surfaces have been reported. Hypopigmentation is a well-recognized adverse effect. In contrast, paradoxical hyperpigmentation has only rarely been documented. In this case report we describe imatinib-induced cutaneous hyperpigmentation and graying of hair occurring in the same patient with dermatofibrosarcoma protuberans treated with imatinib. PMID- 22052280 TI - A case of lichen planus following Tdap vaccination. AB - Lichen planus (LP) is an inflammatory dermatosis of unknown etiology that is primarily associated with liver disease. Recently, there have been several reports of LP developing after administration of the hepatitis B, influenza and combined MMR-DTaP-IPV vaccines. Here we report the first case of LP developing on the lower extremities of an otherwise healthy adult male after administration of the Tdap vaccine. We present this case to draw awareness to this observation in light of recently updated Tdap vaccination recommendations. PMID- 22052281 TI - Iododerma following radioactive iodine ablation of the thyroid for Graves disease. PMID- 22052282 TI - A noduloulcerative disease that still lingers after all these centuries. PMID- 22052283 TI - Onychomycosis: is there a role for lasers? PMID- 22052284 TI - Teledynamic evaluation of oropharyngeal swallowing. AB - PURPOSE: The objective of the present investigation was to test the feasibility and clinical utility of a real-time Internet-based protocol for remote, telefluoroscopic evaluation of oropharyngeal swallowing. METHOD: In this prospective cohort study, the authors evaluated 32 patients with a primary diagnosis of stroke or head/neck cancer. All patients participated in 2 separate fluoroscopic swallowing evaluations--one traditional on site and one telefluoroscopic off site--through the use of a telemedicine system. Agreement between sites was tested for 3 categories of variables: (a) overall severity of swallowing difficulty, (b) presence and extent of laryngeal penetration and aspiration as rated by the 8-point Penetration-Aspiration scale, and (c) treatment recommendations. RESULTS: Results showed overall good agreement in subjective severity ratings (kappa = 0.636) and in Penetration-Aspiration scale ratings (mean absolute difference = 1.1 points) between the onsite and offsite clinicians. Agreement in treatment recommendations was moderate to high, ranging from 69.3% to 100%. CONCLUSIONS: The present study supports the feasibility and clinical utility of a telemedicine system for evaluating oropharyngeal swallowing. Given the difficulty and expertise needed to complete such evaluations, this study offers promising clinical avenues for patients in rural, remote, and underserved communities and countries where expert swallowing specialists are not available. PMID- 22052285 TI - Three-dimensional magnetic resonance imaging of velopharyngeal structures. AB - PURPOSE: To report the feasibility of using a 3-dimensional (3D) magnetic resonance imaging (MRI) protocol for examining velopharyngeal structures. Using collected 3D MRI data, the authors investigated the effect of sex on the midsagittal velopharyngeal structures and the levator veli palatini (levator) muscle configurations. METHOD: Ten Caucasian healthy adults (5 women and 5 men) participated. A whole-head 3D MRI scan was obtained while participants were at rest in the supine position. Basic anatomic parameters of the velopharynx including midsagittal velopharyngeal structures and levator muscle configurations were compared between sexes. RESULTS: Detailed information on the 3D MRI protocol and data analysis method was introduced in the study. On the basis of the data, only the length of the levator muscle showed a statistically significant sex difference: Male participants had significantly longer levator muscles than those of female participants. CONCLUSIONS: The present study successfully demonstrated the use of 3D MRI in quantifying major velopharyngeal structures and provided additional data on the anatomic variations that exist in healthy adult individuals. PMID- 22052287 TI - Specific alterations of carbohydrate metabolism are associated with hepatocarcinogenesis in mitochondrially impaired mice. AB - Friedreich's ataxia is an inherited neurodegenerative disease caused by the reduced expression of the mitochondrially active protein frataxin. We have previously shown that mice with a hepatocyte-specific frataxin knockout (AlbFxn( /-)) develop multiple hepatic tumors in later life. In the present study, hepatic carbohydrate metabolism in AlbFxn(-/-) mice at an early and late life stage was analyzed. In young (5-week-old) AlbFxn(-/-) mice hepatic ATP, glucose-6-phosphate and glycogen levels were found to be reduced by ~74, 80 and 88%, respectively, when compared with control animals. This pronounced ATP, G6P and glycogen depletion in the livers of young mice reverted in older animals: while half of the mice die before 30 weeks of age, the other half reaches 17 months of age and exhibits glycogen, G6P and ATP levels similar to those in age-matched controls. A key event in this respect seems to be the up-regulation of GLUT1, the predominant glucose transporter in fetal liver parenchyma, which became evident in AlbFxn(-/ ) mice being 5-12 weeks of age. The most significant histological findings in animals being 17 or 22 months of age were the appearance of multiple clear cell, mixed cell and basophilic foci throughout the liver parenchyma as well as the development of hepatocellular adenomas and carcinomas. The hepatocarcinogenic process in AlbFxn(-/-) mice shows remarkable differences regarding carbohydrate metabolism alterations when compared with all other chemically and virally driven liver cancer models described up to now. PMID- 22052288 TI - "Seizing" the opportunity to understand antifibrinolytic drugs. PMID- 22052286 TI - An aggregation sensing reporter identifies leflunomide and teriflunomide as polyglutamine aggregate inhibitors. AB - Intracellular protein aggregation is a common pathologic feature in neurodegenerative diseases such as Huntington' disease, amyotrophic lateral sclerosis and Parkinson' disease. Although progress towards understanding protein aggregation in vitro has been made, little of this knowledge has translated to patient therapy. Moreover, mechanisms controlling aggregate formation and catabolism in cellulo remain poorly understood. One limitation is the lack of tools to quantitatively monitor protein aggregation and disaggregation. Here, we developed a protein-aggregation reporter that uses huntingtin exon 1 containing 72 glutamines fused to the N-terminal end of firefly luciferase (httQ72-Luc). httQ72-Luc fails to aggregate unless seeded by a non-luciferase-containing polyglutamine (polyQ) protein such as Q80-cfp. Upon co-aggregation, httQ72-luc becomes insoluble and loses its enzymatic activity. Using httQ72-Luc with Q80(CFP/YFP) as seeds, we screened the Johns Hopkins Clinical Compound Library and identified leflunomide, a dihydroorotate dehydrogenase inhibitor with immunosuppressive and anti-psoriatic activities, as a novel drug that prevents polyQ aggregation. Leflunomide and its active metabolite teriflunomide inhibited protein aggregation independently of their known role in pyrimidine biosynthesis, since neither uridine treatment nor other pyrimidine biosynthesis inhibitors affected polyQ aggregation. Inducible cell line and cycloheximide-chase experiments indicate that these drugs prevent incorporation of expanded polyQ into an aggregate. This study demonstrates the usefulness of luciferase-based protein aggregate reporters for high-throughput screening applications. As current trials are under-way for teriflunomide in the treatment of multiple sclerosis, we propose that this drug be considered a possible therapeutic agent for polyQ diseases. PMID- 22052289 TI - A flexible gel pad as an effective medium for scanning irregular surface anatomy. PMID- 22052296 TI - Response to letter from Dr North. PMID- 22052297 TI - Response to letter from Ms Jane Shipley. PMID- 22052298 TI - Size-controllable APTS stabilized ruthenium(0) nanoparticles catalyst for the dehydrogenation of dimethylamine-borane at room temperature. AB - Dimethylamine-borane, (CH(3))(2)NHBH(3), has been considered as one of the attractive materials for the efficient storage of hydrogen, which is still one of the key issues in the "Hydrogen Economy". In a recent communication we have reported the synthesis and characterization of 3-aminopropyltriethoxysilane stabilized ruthenium(0) nanoparticles with the preliminary results for their catalytic performance in the dehydrogenation of dimethylamine-borane at room temperature. Herein, we report a complete work including (i) effect of initial [APTS]/[Ru] molar ratio on both the size and the catalytic activity of ruthenium(0) nanoparticles, (ii) collection of extensive kinetic data under non MTL conditions depending on the substrate and catalyst concentrations to define the rate law of Ru(0)/APTS-catalyzed dehydrogenation of dimethylamine-borane at room temperature, (iii) determination of activation parameters (E(a), DeltaH(#) and DeltaS(#)) for Ru(0)/APTS-catalyzed dehydrogenation of dimethylamine-borane; (iv) demonstration of the catalytic lifetime of Ru(0)/APTS nanoparticles in the dehydrogenation of dimethylamine-borane at room temperature, (v) testing the bottlability and reusability of Ru(0)/APTS nanocatalyst in the room-temperature dehydrogenation of dimethylamine-borane, (vi) quantitative carbon disulfide (CS(2)) poisoning experiments to find a corrected TTO and TOF values on a per active-ruthenium-atom basis, (vii) a summary of extensive literature review for the catalysts tested in the catalytic dehydrogenation of dimethylamine-borane as part of the results and discussions. PMID- 22052300 TI - Editorial: JDD receives impact factor ranking: 1.954. PMID- 22052299 TI - Early intraperitoneal metabolic changes and protease activation as indicators of pancreatic fistula after pancreaticoduodenectomy. AB - BACKGROUND: Ischaemia and local protease activation close to the pancreaticojejunal anastomosis (PJA) are potential mechanisms of postoperative pancreatic fistula (POPF) formation. To provide information on the pathophysiology of POPF, intraperitoneal microdialysis was used to monitor metabolic changes and protease activation close to the PJA after pancreaticoduodenectomy (PD). METHODS: In patients who underwent PD, intraperitoneal metabolites (glycerol, lactate, pyruvate and glucose) were measured by microdialysis, and lactate and glucose in blood were monitored, every 4 h for 5 days, starting at 12.00 hours on the day after surgery. Trypsinogen activation peptide (TAP) was measured in microdialysates as a marker of protease activation. RESULTS: Intraperitoneal glycerol levels and the ratio of lactate to pyruvate were higher after PD and glucose levels were lower in seven patients who later developed symptomatic POPF than in eight patients with other surgical complications (OSC) and 33 with no surgical complications (NSC) (all P < 0.050). TAP was detected at a concentration greater than 0.1 ug/l in six of seven patients with POPF, two of eight with OSC and two of 33 with NSC. Intraperitoneal lactate concentrations were higher than systemic levels in all patients on days 1 to 5 after surgery (P < 0.001). In patients with POPF, high intraperitoneal lactate concentrations were observed without systemic hyperlactataemia. CONCLUSION: Early in the postoperative phase, patients who later developed clinically significant POPF had higher intraperitoneal glycerol concentrations and lactate/pyruvate ratios, and lower glucose concentrations in combination with a TAP level exceeding 0.1 ug/l close to the PJA, than patients who did not develop POPF. PMID- 22052301 TI - Advances in laser hair removal in skin of color. AB - Laser hair removal, previously contraindicated in patients with ethnically dark (phototypes IV-VI) or sun-tanned skin, is now recognized as a safe and effective method of permanent hair reduction in all patients. Longer wavelengths, conservative fluences, longer pulse durations and appropriate cooling methods are necessary to minimize untoward side effects and maximize efficacy. The longer wavelength Nd:YAG laser is considered safest in treating darker skin of color. An added benefit of laser epilation is that side effects of conventional hair removal such as pseudo-folliculitis barbae and post inflammatory dyspigmentation, more commonly seen in skin of color, may also respond favorably to the laser, thus increasing the potential for patient satisfaction. PMID- 22052302 TI - Treatment of actinic cheilitis by photodynamic therapy with 5-aminolevulinic acid and blue light activation. AB - Actinic cheilitis (AC), a common disorder of the lower lip, should be treated early to prevent progression to invasive squamous cell carcinoma. This study evaluated the safety and efficacy of photodynamic therapy (PDT) with 5 aminolevulinic acid (ALA) activated by blue light for the treatment of AC. Fifteen patients with clinically evident or biopsy-proven AC received two treatments with ALA PDT with blue light activation. Treatments were spaced three to five weeks apart. Most patients achieved 65% to 75% clearance three to five weeks after the first treatment and all achieved more than 75% clearance one month after the second treatment. Three patients achieved complete clearance. Pain and burning during irradiation were absent or mild. All patients said they would repeat the procedure. ALA PDT with 417 nm blue light is a promising option for the treatment of AC of the lower lip. PMID- 22052303 TI - Intense pulsed light photorejuvenation: a histological and immunohistochemical evaluation. AB - BACKGROUND: The use of intense pulsed light (IPL) for facial rejuvenation had been the topic of many studies. However, few of them discussed quantitative changes in extracellular matrix proteins after IPL therapy. OBJECTIVE: To objectively quantify the histological changes in extracellular matrix proteins after IPL treatment for facial wrinkles. METHODS: Biopsy specimens were obtained from the periocular area of six volunteers of Fitzpatrick skin type III-IV and Glogau's class I-III wrinkles. They were subjected to three months of IPL treatment (six sessions at two-week intervals). Using histological and immunostaining analysis coupled with computerized morphometric analysis, quantitative evaluation of collagen types I, III and VII, newly synthesized collagen, total elastin and tropoelastin was performed for skin biopsies at baseline, end of treatment, and three months post-treatment. RESULTS: Clinical assessment of volunteers did not show clinically noticeable improvement in facial wrinkles after IPL treatment. Furthermore, quantitative evaluation of extracellular matrix proteins showed no statistically significant changes (P>0.05) in response to IPL treatment CONCLUSION: Although 50 percent of volunteers showed mild improvement in skin texture at the end of IPL treatment, none of them reported improvement in skin tightening or wrinkles. No statistically significant histological changes were observed three months post IPL treatment. PMID- 22052304 TI - Comparison between sequentional treatment with diode and alexandrite lasers versus alexandrite laser alone in the treatment of hirsutism. AB - Laser systems that are commonly used for the treatment of hirsutism include the ruby laser (694 nm), the diode laser (800 nm), the alexandrite laser (755 nm) and the Nd:YAG laser (1084 nm). The diode laser and alexandrite laser are considered effective in treatment of hirsutism in dark-skinned patients. The response of hairs to these laser systems is variable and not complete. In this study, we compared the efficacy of these two laser systems for permanent hair removal. This was a randomized, controlled clinical trial that was performed with women of the age range 15-45 years old. After obtaining informed consent, the samples were randomized into two groups using random allocation software. The first group was treated with alexandrite laser alone (four sessions, two months apart). The second group was treated sequentially with diode laser for the first two sessions and alexandrite laser for the next two sessions. Overall, 111 patients (57 patients in the alexandrite laser group and 54 patients in the sequential diode alexandrite laser group) were evaluated. There was no significant difference regarding mean of hair reduction between the two groups during the courses of treatment. Except for the first session, there was no significant difference regarding percent of patient satisfaction between the two groups (P value >0.05). Comparison between the two groups showed no significant difference one month, three months and six months after the last treatment (P value >0.05). Regarding the results of our study, there is no significant difference between sequential treatment with diode and alexandrite lasers versus alexandrite laser alone in the treatment of hirsutism. We suggest that in further studies, the efficacy of sequential treatment with other laser systems is evaluated against single treatment methods. PMID- 22052305 TI - A pilot study using reflectance confocal microscopy (RCM) in the assessment of a novel formulation for the treatment of melasma. AB - INTRODUCTION: Melasma is a common pigmentary disorder caused by abnormal melanin deposits within the skin. Hydroquinone (HQ) is presently the most popular depigmenting agent, however the treatment of melasma remains unsatisfactory, resulting in a need to evaluate new depigmenting agents. OBJECTIVE: The objective of this study was to assess, using standard methods and a novel technique, in vivo Reflectance Confocal Microscopy (RCM), the efficacy and safety of a new non HQ bleaching agent Dermamelan(r) (Mesoestetic, Barcelona, Spain) in the treatment of melasma. METHODS: Ten women with melasma were enrolled in an open-label trial lasting four months. Patients were of Fitzpatrick skin types II-IV. A non-HQ depigmenting agent (Dermamelan) was applied once-daily for three months. Melasma Area and Severity Indices (MASI) were measured. Standard and UV-light photographs were taken and in vivo RCM, which detects pigmentary changes at a cellular level, was done. Evaluations were performed before treatment, on the first, second and third month of treatment and one month after treatment. Upon cessation of the trial, patients completed a questionnaire regarding efficacy and tolerance. RESULTS: At baseline, RCM detected hyperpigmented keratinocytes in all patients, dendritic cells in 2/10 patients, and melanophages in 2/10 patients. Based on the MASI score, Dermamelan treatment improved melasma by 50 percent. This was confirmed by standard and UV-light photography. Maximum therapeutic effect was usually reached by one month of treatment and was maintained at one month following its completion. Interestingly Dermamelan treatment also induced a statistically significant decrease of pigmented epidermal keratinocytes as detected by RCM. Patients with melanophages on RCM at baseline had a poorer outcome, but not those with dendritic cells. Mild irritation was the only adverse event observed during treatment. The majority of patients were satisfied with the result. CONCLUSION: This study suggests that Dermamelan produces significant rapid improvement of melasma at a clinical and cellular level and demonstrates the potential of RCM to monitor and possibly predict efficacy of a new depigmenting agent in the treatment of melasma. PMID- 22052306 TI - A multiplexed 1,440 and 1,320 nm laser for treatment of chronic photodamage. AB - BACKGROUND AND OBJECTIVES: The purpose of this study is to quantify the safety and effectiveness of a multiplexed 1,440 and 1,320 nm fractionated laser for the treatment of chronic photodamage. STUDY DESIGN: A total of twenty subjects with chronic photodamage were enrolled in this study. Subjects received a maximum of four full-face treatments at an average fluence of 9.5 J/cm2 at 1,320 nm and 2 J/cm2 at 1,450 nm, delivered sequentially using forced-air cooling, at monthly intervals. Digital photographs were taken two months following the final treatment and compared to pre-treatment photographs by two blinded physician observers. RESULTS: Improvement in photodamage, overall appearance, wrinkles, hyper-pigmentation, enlarged pores, and sagging skin was rated by blinded physician evaluation of digital photographs as being in the 25-50 percent range. Subjective ratings averaged improved for all criteria that were evaluated, including wrinkles, enlarged pores, redness, sagging skin and hyper-pigmentation. CONCLUSIONS: The multiplexed 1,320 nm and 1,440 nm fractionated laser improves cutaneous photodamage as assessed by objective and subjective criteria. PMID- 22052307 TI - 3D Mohs surgery: a new concept. AB - Although Mohs surgery is considered a skin-sparing technique, when dealing with aggressive skin tumor that penetrates the deep tissues, the Mohs surgeon usually sacrifices uninvolved skin. We present our technique of 3D Mohs as a new concept for skin-sparing surgery. After raising a skin flap above the residual tumor, Mohs resection was performed on the deep tissues horizontally and simultaneously on the inner plan of the flap vertically. When "clear" borders were achieved, the skin flap was sutured back into place. The results show that the defect was significantly smaller, and the hair on the Mohs-treated vertical flap continue to grow, thus contributing to a more aesthetic outcome. We conclude that careful use of the 3D Mohs technique as we describe spares the healthy uninvolved skin and offers better aesthetic and functional result. PMID- 22052308 TI - The tower technique: a novel technique for the injection of hyaluronic acid fillers. AB - A number of injection techniques have been described for the placement of hyaluronic acid fillers. Such techniques include, but are not limited to, linear threading, depot, fanning, and layering. The tower technique for hyaluronic acid filler injection is a novel variation of the depot and layering techniques. With this technique, the hyaluronic acid is deposited via a perpendicular approach to the deep tissue plane with a gradual tapering of product deposition as the needle is withdrawn. A series of towers or struts are thus created. These towers serve as support structures for the overlying soft tissue, thereby restoring the face to a more youthful appearance. The anatomic areas most amenable to this technique include the lateral brow, the nasolabial folds, the marionette lines, the prejowl sulcus, and the mental region. A detailed description of the tower technique for facial volume restoration with hyaluronic acid fillers is provided. Further prospective studies are needed to compare the efficacy, safety, and longevity of this technique to other commonly used techniques for the injection of hyaluronic acid fillers. PMID- 22052311 TI - A review of the chemopreventative effects of oral retinoids for internal neoplasms. AB - With the recent data showing that psoriasis patients are at higher risk for systemic malignancies, there is a growing awareness for the need to minimize cancer risks in psoriasis patients. Retinoids as a class of medication have been widely studied as potential agents for cancer chemoprevention. Since they act by inducing cell differentiation and maturation, they may help reverse the pathogenesis of malignancies. Through an extensive literature review, this paper provides an update on the available data on retinoids and their systemic anti cancer properties. Retinoids appear to be beneficial in the prevention of cutaneous T-cell lymphoma, acute promyelocytic leukemia, head and neck cancers, hepatocellular carcinoma, breast cancer and neuroblastoma. So far the data does not support anti-cancer efficacy of retinoids in the prevention of prostate or pancreatic cancer and may possibly have harmful effects in the pathogenesis of lung cancer in smokers. J Drugs Dermatol. 2011;10(11):1292-1298. PMID- 22052309 TI - A randomized, double-blind, vehicle-controlled efficacy and safety study of naftifine 2% cream in the treatment of tinea pedis. AB - OBJECTIVE: Naftifine HCl 2% cream (NAFT-2) is a topical allylamine antifungal agent under development in the United States. This randomized, double-blind, vehicle-controlled, phase 3 trial evaluated the efficacy and safety of two weeks of NAFT-2 treatment in subjects with tinea pedis. Naftifine 1% cream (NAFT-1) treatment for four weeks and vehicle were also evaluated as a positive control. METHODS: 709 subjects were randomly assigned 2:1:2:1 to one of four treatment groups: (i) NAFT-2 (n= 235), (ii) two-week vehicle (n=118), (iii) NAFT-1 (n=237), or (iv) four-week vehicle (n=119). Efficacy was evaluated at baseline, week 2, week 4, and week 6 and consisted of mycology determination (KOH and dermatophyte culture) and scoring of clinical symptom severity (erythema, scaling, and pruritus). Efficacy was only analyzed in 425 subjects with positive baseline dermatophyte culture. Safety was evaluated by adverse events (AE) and laboratory values in 707 subjects. RESULTS: At week 6, NAFT-2 subjects achieved 18 percent complete cure rate, 67 percent mycological cure rate, 57 percent treatment effectiveness, 22 percent clinical cure rate, and 78 percent clinical success rate compared to respective vehicle rates of seven percent (one-sided, P<0.01), 21 percent (P<0.001), 20 percent (P<0.001), 11 percent (P=0.04) and 49 percent (P<0.001). Week 6 efficacy responses in NAFT-1-treated subjects were significantly higher than vehicle subjects and almost identical to NAFT-2 subjects. Mycological cure and clinical response rates in both NAFT-2 and NAFT-1 increased from week 2 to week 6. Treatment-related AEs occurred in five percent of NAFT-2 subjects, seven percent of vehicle subjects, four percent of NAFT-1 subjects and eight percent of vehicle subjects. The most common AEs for all groups were application site pruritus and skin irritation. CONCLUSION: Topical NAFT-2 for two weeks is safe and provides significantly superior antifungal treatment than vehicle in tinea pedis subjects. NAFT-2 produces equivalent efficacy responses to four weeks of NAFT-1 treatment. The fungicidal activity of naftifine continues to increase for at least one month after treatment is completed. (Clinical Trials Identification Numbe=NCT00750139). J Drugs Dermatol. 2011;10(11):1282-1288. PMID- 22052312 TI - Imiquimod: a review of off-label clinical applications. AB - The immunomodulatory characteristics and topical application of imiquimod (IQ), a toll-like receptor 7 agonist, have lead to extensive off-label therapeutic trials. Off-label use is not uncommon in dermatology. However, clinicians must make informed decisions to ensure safe and effective implementation when standardized protocols are lacking. We present the highest level of clinical evidence for each off-label application of IQ, summarize management steps, treatment regimens, and results. We hope consolidation of this information will facilitate implementation of informed and evidence-based clinical decisions. Forty-six off-label applications were reported. Treatments were generally applied in the same manner, tailored to induce an inflammatory response and reduced with the development of adverse reactions. The efficacy of imiquimod ranged from promising to suboptimal compared to standard treatments and protocols. Clinicians who choose to use IQ off-label should have a firm understanding of the extent an application has been studied and how to manage adverse events. PMID- 22052313 TI - Hair regrowth following a Wnt- and follistatin containing treatment: safety and efficacy in a first-in-man phase 1 clinical trial. AB - Research has shown the importance of follistatin, Wnt 7a, and wound healing growth factors on the stimulation of bulge cells and inter-follicular stem cells to induce hair growth. We have studied the effects of a bioengineered, non recombinant, human cell-derived formulation, termed Hair Stimulating Complex (HSC), containing these factors to assess its hair growth activity in male pattern baldness. HSC showed in vitro Wnt activity and contained follistatin, KGF, and VEGF. The clinical study was a double-blind, placebo-controlled, randomized single site trial and was designed to evaluate safety of the HSC product and assess efficacy in stimulating hair growth. All 26 subjects tolerated the single, intradermal injection of HSC procedures well, and no signs of an adverse reaction were reported. Histopathological evaluation of the treatment site biopsies taken at 22 and 52 weeks post-treatment revealed no abnormal morphology, hamartomas, or other pathological responses. Trichoscan image analysis of HSC-treated sites at 12 and 52 weeks showed significant improvements in hair growth over the placebo. At the initial 12-week evaluation period, HSC treated sites demonstrated an increase in hair shaft thickness (6.3%+/-2.5% vs. 0.63%+/-2.1%; P=0.046), thickness density (12.8%+/-4.5% vs. -0.2%+/-2.9%; P=0.028), and terminal hair density (20.6+/-4.9% vs. 4.4+/-4.9%; P=0.029). At one year, a statistically significant increase in total hair count (P=0.032) continued to be seen. These results demonstrate that a single intradermal administration of HSC improved hair growth in subjects with androgenetic alopecia and is a clinical substantiation of previous preclinical research with Wnts, follistatin, and other growth factors associated with wound healing and regeneration. PMID- 22052315 TI - Q-switched laser treatment of amiodarone pigmentation. AB - A number of drugs can cause cutaneous hyperpigmentation through a variety of mechanisms. The pigment is comprised of dermal deposits of the drug and its metabolites, often combined with melanin and hemosiderin. Minocycline and amiodarone are among the most common medications to cause skin-induced pigmentation. Affected individuals generally develop slate-gray pigmentation in affected sites. Treatment with various Q-switched lasers has been shown to be effective at removing drug-induced pigmentation. The author presents a man with amiodarone pigmentation of the face who responded to treatment with the Q switched neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. PMID- 22052316 TI - Multiple facial burns with the new Thermage CPT system. AB - A 45-year-old man requested treatment with Thermage for skin tightening. He was treated with the new Thermage CPT system and received several facial burns due to failure of the dielectric membrane. It may be contraindicated to treat male patients with this system. PMID- 22052317 TI - Mohs micrographic surgery for the treatment of cutaneous lymphadenoma. AB - Cutaneous lymphadenoma (CL) is a benign neoplasm commonly presenting on the head and neck of young and middle-aged adults. Complete surgical excision of CL is the treatment of choice and appears to be curative. As compared to local excision without margin control, Mohs micrographic surgery (MMS) may allow for more definitive tumor extirpation for large cases of CL and allow for greater tissue preservation at functionally and aesthetically sensitive sites. We present a case of cutaneous lymphadenoma presenting on the right cheek of a middle-aged male who was successfully treated with MMS. PMID- 22052318 TI - Bullous pemphigoid after herpes zoster vaccine administration: association or coincidence? AB - The development of autoimmune disorders and an increase in autoimmune phenomena have been reported following vaccinations in a number of cases. Blistering skin disorders such as pemphigus vulgaris (PV) and bullous pemphigoid (BP) have also developed following various vaccinations.1,2 Here we describe a case of BP that developed in a 72-year-old male after receiving the zoster vaccine. We believe the association between zoster immunization and the acute onset of BP in our patient may not be coincidental. We further discuss proposed mechanisms leading to autoimmunity post vaccination. PMID- 22052319 TI - Chloracne-like drug eruption associated with sorafenib. AB - Sorafenib is a chemotherapeutic agent primarily used to treat metastatic renal cell carcinoma. It is a multikinase inhibitor that blocks cell proliferation and angiogenesis. Numerous cutaneous side effects have been reported in association with this medication, including acral erythema, inflammation of actinic keratoses, erythema multiforme, vasculitis, and keratoacanthomas. Up to 40 percent of patients on this medication develop dermatologic manifestations. We describe chloracne-like eruptions in two different patients with no exposure to aromatic hydrocarbons but who were recently started on sorafenib for treatment of metastatic renal carcinoma. The primary reason for discontinuation of sorafenib is secondary to its adverse side effect profile. Recognizing these effects early and administering appropriate treatment will likely increase medication compliance and minimize both dose reductions and discontinuation of the medication resulting in optimal treatment outcomes. PMID- 22052320 TI - Resident rounds. Part III. Erosive and desquamative syphilis associated with mucositis in the setting of acquired immune deficiency syndrome. PMID- 22052324 TI - Understanding medical malpractice insurance: a primer. AB - As the policy debate over the medical malpractice insurance crisis continues, dueling claims about its causes and suggestions for policy solutions have highlighted the need for a better understanding of how medical malpractice insurance works, why premiums change and what can be done about it. This primer on malpractice insurance discusses these issues and also analyzes the causes of and potential solutions to address malpractice crises. Key issues include: Rate regulation may have an important influence on insurance prices, but whether it raises or lowers them is not clear. Rising claims costs driven by an increase in average payments not claims frequency have contributed to rising premiums, but do not explain the sudden spike in premiums around 1999-2000. Along with claims costs, the insurance cycle has contributed to the current crisis. PMID- 22052325 TI - Hormone therapy use and mammographic density in postmenopausal Norwegian women. AB - While studies have shown that use of postmenopausal hormone therapy with estrogen and progestogen (EPT) increases mammographic density, aspects of this association remain unclear. We examined whether mammographic density differed by type of hormone therapy (HT) used, dose, duration of use, time since last use, and whether the effects are modified by age and body mass index (BMI). Using a cross sectional design, we recruited 2,424 postmenopausal women aged 50-69 years participating in the Norwegian Breast Cancer Screening Program. Mammographic density was assessed with a computer-assisted method, and we estimated mean absolute and percent mammographic density through multiple linear regression, and adjusting for possible confounders. Mammographic density was higher among current HT users (percent density: 22.6%; 95% CI: 22.1-23.2%) than among former (17.7%; 17.2-18.2%) or never users (16.3%; 15.7-16.8%). The highest density was seen in current EPT users of high-dose norethisterone acetate (NETA) regimens who had a percent density of 26.2% (24.3-28.1%). Results differed when considering the combined effect of age and BMI. The effect of EPT on mammographic density was modified by age and BMI, with no apparent association among the youngest women (aged 50-55) with the highest BMI (BMI >= 26). A higher mammographic density was found in EPT users compared to never HT users, particularly in women using high dose NETA regimens. Age and BMI modified the association between EPT use and mammographic density. PMID- 22052326 TI - Identification of copy number alterations associated with the progression of DCIS to invasive ductal carcinoma. AB - Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive ductal carcinoma (IDC). Annotation of the genetic differences between the two lesions may assist in the identification of genes that promote the invasive phenotype. Synchronous DCIS and IDC cells were microdissected from FFPE tissue and analysed by molecular inversion probe (MIP) copy number arrays. Matched IDC and DCIS showed highly similar copy number profiles (average of 83% of the genome shared) indicating a common clonal origin although there is evidence that the DCIS continues to evolve in parallel with the co-existing IDC. Four chromosomal regions of loss (3q, 6q, 8p and 11q) and four regions of gain (5q, 16p, 19q and 20) were recurrently affected in IDC but not in DCIS. CCND1 and MYC showed increased amplitude of gain in IDC. One region of loss (17p11.2) was specific to DCIS. IDC-specific regions include genes with previous links to breast cancer progression and potential therapeutic targets such as AXL, SPHK1 and PLAUR. PMID- 22052327 TI - Detection of a large rearrangement in PALB2 in Spanish breast cancer families with male breast cancer. AB - It has been demonstrated that monoallelic PALB2 (Partner and Localizer of BRCA2) gene mutations predispose to familial breast cancer. Some of the families reported with germline PALB2 mutations presented male breast cancer as a characteristic clinical feature. Therefore, we wanted to investigate the contribution of germline PALB2 mutations in a set of 131 Spanish BRCA1/BRCA2 negative breast/ovarian cancer families with at least one male breast cancer case. The analysis included direct sequencing of all coding exons and intron/exon boundaries as well as a Multiplex Ligation-dependent Probe Amplification-based analysis of genomic rearrangements. For the first time we have identified a genomic rearrangement of PALB2 gene involving a large deletion from exon 7 to 11 in a breast cancer family. We have also identified several PALB2 variants, but no other obvious deleterious PALB2 mutation has been found. Thus, our study does not support an enrichment of PALB2 germline mutations in the subset of breast cancer families with male breast cancer cases. The identification of intronic and exonic variants indicates the necessity of assessing the implications of variants that do not lead to PALB2 truncation in the pathoghenicity of the PALB2 gene. PMID- 22052328 TI - Polychlorinated biphenyl congeners in river sediments: distribution and source identification using multivariate factor analysis. AB - To assess the level of polychlorinated biphenyl (PCB) contamination and identify their sources, surface sediments were collected from selected locations along Nakdong River, Korea, and analyzed for 209 PCB congeners using high-resolution gas chromatography/high-resolution mass spectroscopy. PCB levels ranged from 0.124 to 79.2 ng/g dry weight (coplanar PCBs 0.295 to 5720 pg/g dry), which were similar to those of three other major rivers (Han, Geum, and Youngsan rivers) in Korea but slightly lower than those in neighboring countries. Regarding homologue composition, tetra-CBs were most abundant in most samples, but some samples with much higher PCBs concentrations had relatively lower proportions of tetra-CBs and higher proportions of penta- to hepta-CBs. To identify the sources of PCBs in sediment samples, principal component analysis/absolute principal component scores (PCA/APCS), positive matrix factorization (PMF), and multiple linear regression (MLR) were used with the congener composition of aroclors (1242, 1248, 1254, and 1260) and the flue gas of waste incinerators (data obtained from a previous article) as source profiles. Results showed that the three models showed similar source apportionments. Most sediment samples with lower PCB concentrations had higher proportions of incineration-derived materials, and some sediment samples with much higher PCB concentrations had higher proportions of aroclor 1260. This occurred because many industrial facilities, such as landfill leachate-treatment facilities, were gathered around sampling points with high PCB concentrations, and high-chlorinated PCBs are more stable in the elution process of landfill leachate than the incineration process. PCB concentrations estimated by APCS, PMF, and MLR were similar to the measured values with coefficients of determination ranging from 0.77 to 0.99. PMID- 22052330 TI - Reversal of fetal ductal constriction after maternal restriction of polyphenol rich foods: an open clinical trial. AB - OBJECTIVE: To test the hypothesis that maternal restriction of polyphenol-rich foods (PRF), which, like non-steroidal anti-inflammatory drugs (NSAID), inhibit prostaglandin synthesis in the third trimester, reverse fetal ductal constriction (DC). STUDY DESIGN: An open clinical trial of 51 third trimester fetuses with DC with no history of NSAID intake was designed. All mothers were submitted to a food frequency questionnaire and were oriented to withdrawl PRF, being reassessed after 3 weeks. Doppler parameters were assessed before and after discontinuation of these substances. A control group of 26 third trimester normal fetuses, with no ductus arteriosus (DA) constriction, in which no dietary intervention was offered, was reviewed after 3 weeks. Student's t-test and Wilcoxon's test were used. RESULT: Mean gestational age was 32+/-3 weeks (28 to 37 weeks). After discontinuation of PRF (>=3 weeks), 48/51 fetuses (96%) showed complete reversal of DC, with decrease in mean ductal systolic velocity (1.74+/-0.20 m s(-1) to 1.31+/-0.34 m s(-1), P<0.001), mean diastolic velocity (0.33+/-0.09 m s(-1) to 0.21+/-0.07 m s(-1), P<0.001) and mean right to left ventricular dimension ratio (1.37+/-0.26 to 1.12+/-0.17, P<0.001) and increase in mean ductal pulsatility index (PI) (1.98+/-0.36 to 2.46+/-0.23, P<0.001). Median daily maternal consumption of PRF was 286 mg per day and decreased after orientation to 0 mg per day, P<0.001. In the control group, with GA of 32+/-4 w (29-37 w), there was no significant differences in median daily maternal consumption of PRF, mean ductal systolic velocitiy, diastolic velocity, PI and right ventricular to left ventricular diameter ratio (RV/LV) ratio. CONCLUSION: Reduction of maternal PRF intake during pregnancy, especially in the third trimester, is followed by complete reversal of DC (wide open DA), which may influence maternal dietary habits in late pregnancy. PMID- 22052329 TI - Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies. AB - Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8-143.2) for SqCC, 111.3 (95% CI: 69.8-177.5) for SCLC and 21.9 (95% CI: 16.6-29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5-124.6), 108.6 (95% CI: 50.7-232.8) and 16.8 (95% CI: 9.2-30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development. PMID- 22052331 TI - Umbilical arterial catheter insertion length: in quest of a universal formula. AB - OBJECTIVE: The study was aimed at comparing the accuracy in length of insertion of umbilical arterial catheter in all new born groups stratified according to weight, by using two different methods, that is, Wright et al./Case (Group I): (4 * Body wt (BW) (kg)) +7; Shukla et al./Control (Group II): (3 * BW (kg)) +9. STUDY DESIGN: It was a randomized open label case control study in a Level III tertiary level Neonatal Intensive Care Unit over 9 months. RESULT: The babies in both the groups were similar in relation to weight, gender, prematurity and weight subgroups. Under insertion was seen in 8% (4/50) of babies in group I and over insertion was seen in group II where it was 32.6% (16/49). There was a reduction of 82% abnormal insertions and repositioning by using the Wright's formula as compared with the Shukla's formula in preterm babies. Statistically significant reduction in repositioning was seen in all babies <1500 g in Group I and under insertion seen in 8% of babies in group I did not attain statistical significance (P=0.34). CONCLUSIONS: There is no universal formula, which gives the accurate length of placement of an umbilical arterial catheter, but Wright's formula comes closer in neonates with different weight sub groups. PMID- 22052332 TI - Insulin-induced mTOR activity exhibits anti-hepatitis C virus activity. AB - The mammalian target of rapamycin (mTOR) is one of the influential molecules for the anti-hepatitis C virus (HCV) action of interferon (IFN). IFN-induced mTOR activity, independent of phosphatidylinositol-3-kinase (PI3K) and Akt, is a critical factor for anti-HCV activity. mTOR activity is involved in signal transducers and activators of transcription (STAT)-1 phosphorylation and nuclear localization, and then double-stranded RNA-dependent protein kinase (PKR) is expressed in hepatocytes. Insulin (INS) is a major cytokine for metabolism and regulates the PI3K-Akt-mTOR signaling pathway in hepatocytes. Changes in mTOR activity have been reported in chronic HCV-infected patients with excess nutrition and INS resistance. Therefore, this experiment investigated whether INS increases anti-HCV activity via mTOR activity. This study used a genome-length HCV RNA (strain O of genotype 1b) replicon reporter system (OR6), derived from HuH7 cells. OR6 cells were pre-treated with rapamycin or LY294002 or siRNA, and the cells were treated with INS (0-300 nmol/l) or IFN (0-50 IU/ml) for 30 min to 48 h. The cells were lysed and analyses were carried out using the Renilla luciferase assay, western blotting or ELISA. INS induced the anti-HCV effects via mTOR activity, independently of STAT-1 tyrosine phosphorylation, in a dose- and time-dependent manner. INS-induced mTOR activation was found to be PI3K-Akt dependent in OR6 cells. The combination of IFN and INS had an additive anti-HCV effect. The INS-induced mTOR activity was identified to be an anti-HCV signal independent of the STAT pathway in this study. mTOR activity may be associated with the HCV life cycle. Future studies should, therefore, attempt to identify new agents that activate mTOR to promote anti-HCV activity. PMID- 22052333 TI - Growth inhibition of malignant glioblastoma by DING protein. AB - Malignant gliomas are a highly aggressive type of brain tumor with extremely poor prognosis. These tumors are highly invasive and are often surgically incurable and resistant to chemotherapeutics and radiotherapy. Thus, novel therapies that target pathways involved in growth and survival of the tumor cells are required for the treatment of this class of brain tumors. Previous studies revealed that epidermal growth factor receptor and extracellular-signal-regulated kinases (ERKs), which are involved in the induction of cell proliferation, are activated in the most aggressive type of glioma, i.e. glioblastoma multiforme (GBM). In fact, GBMs with increased levels of ERK activity exhibit a more aggressive phenotype than the others with moderate ERK activity, pointing to the importance of ERK and its kinase activity in the development and progression of these tumors. In this study, we have evaluated the effect of p38SJ, a novel member of the DING family of proteins, derived from Hypericum perforatum calluses, on the growth of malignant glioma cell lines, T98G and U-87MG by focusing on cell cycle and signaling pathways controlled by phosphorylation of various regulatory proteins including ERK. p38SJ, which exhibits profound phosphatase activity, shows the capacity to affect the phosphorylation status of several important kinases modulating signaling pathways, and cell growth and proliferation. Our results demonstrate that p38SJ reduces glioma cell viability and arrests cell cycle progression at G0/G1. The observed growth inhibitory effect of p38SJ is likely mediated by the downregulation of several cell cycle gatekeeper proteins, including cyclin E, Cdc2, and E2F-1. These results suggest that p38SJ may serve as a potential candidate for development of a therapeutic agent for the direct treatment of malignant gliomas and/or as a potential radiosensitizer. PMID- 22052334 TI - Convection-enhanced delivery catheter placements for high-grade gliomas: complications and pitfalls. AB - Convection-enhanced delivery (CED) of compounds into brain tumors reportedly circumvents the blood brain barrier. CED intends to increase drug delivery to malignant cells, reaching high local therapeutic concentration and decreasing or eliminating systemic side effects. Clinical experience and published data on catheter placement (CP) surgery are scarce. We propose practical and technical guidelines for planning CED based on our experience. We retrospectively analyzed the medical charts and relevant neuroimages of 25 patients following the insertion of 64 CED catheters. The patients were enrolled in at least one of four clinical trials using CED for treating recurrent glioblastoma multiforme in our institution between 2003-2006. Intra- and postoperative complications related to CP surgery and the difficulties and pitfalls of planning were evaluated. There were 29 CP surgeries. Forty-four peritumoral brain tissue catheters were inserted in 16 CP surgeries following tumor resection in 16 patients, and 20 catheters were placed into the tumor in 13 procedures in 10 patients. The lesions were in or near eloquent brain tissue areas in 13 of all CP surgeries. Complications included increased edema (31%), infection (6.9%), bleeding (6.9%) and seizures (13.8%). Significant neurological deterioration occurred in 4 patients (13.8%). Difficulties in adhering to CP surgery guidelines included lesion site (superficial, mesial temporal lobe, proximity to CSF spaces), proximity to eloquent cortical areas, tissue density that interfered with the trajectory, and technical limitations of stereotactic instruments. CED procedures for high-grade gliomas may be associated with surgical morbidity. Adherence to guidelines might be difficult because of lesion site and complicated by brain and tumor tissue characteristics. This should be considered while planning clinical trials that use convection-based technology. PMID- 22052335 TI - Anaphylaxis with Latrodectus antivenin resulting in cardiac arrest. AB - Latrodectus mactans antivenin is a safe and effective therapy for severe black widow spider envenomations when given to most patients. We report a case of a 37 year-old male with a history of asthma that was given L. mactans antivenin for symptoms related to a black widow envenomation and developed a severe anaphylactic reaction resulting in cardiac arrest. When traditional therapies failed, the patient was given methylene blue for anaphylactic shock resulting in a 30-h period of hemodynamic stability. Despite initial resuscitation, the patient ultimately died 40 h after presentation. Under the right circumstances, L. mactans antivenin remains a safe and effective therapy for severe black widow envenomations. However, anaphylaxis is a risk for those receiving this therapy, even when the antivenin is diluted and given as an infusion. We report the first death related to diluted L. mactans antivenin given as an infusion. PMID- 22052336 TI - Outcomes following surgery without radiotherapy for rectal cancer. AB - BACKGROUND: This study determined survival and recurrence rates following curative resection of rectal cancer without radiotherapy. METHODS: This was a retrospective review of the Mayo Clinic database of patients with rectal cancer treated with curative intent using surgery alone from 1990 to 2006. Patients who received neoadjuvant chemotherapy or radiation therapy and those who had any postoperative radiotherapy were excluded. Details were collected from the database and patient records using a protocol approved by the institutional review board. RESULTS: Some 655 consecutive patients with rectal cancer treated with curative intent using surgery alone were identified; 397 had stage I disease, 125 stage II and 133 stage III. Four hundred and nine patients underwent anterior resection (AR) and 246 abdominoperineal resection (APR). Median follow up was 62 months. The 5-year rate of local recurrence was 4.3 per cent, disease free survival 90.0 per cent and cancer-specific survival 91.5 per cent. Stage specific and all-stage disease-free survival did not differ significantly between AR and APR. The 5-year cumulative local recurrence rate was lower following AR than APR (3.6 versus 5.5 per cent; P = 0.321). There were only two patients with positive margins and type of operation was not significant on multivariable analysis. CONCLUSION: Well-performed, standardized APRs have similar local recurrence to AR. Radiation therapy may not confer much additional benefit. PMID- 22052337 TI - MicroRNAs in hypertension: mechanisms and therapeutic targets. AB - Hypertension is a complex, multifactorial disease, and its development is determined by a combination of genetic susceptibility and environmental factors. Several mechanisms have been implicated in the pathogenesis of hypertension: increased activity of the sympathetic nervous system, overactivation of the renin angiotensin aldosterone system (RAAS), dysfunction of vascular endothelium, impaired platelet function, thrombogenesis, vascular smooth muscle and cardiac hypertrophy, and altered angiogenesis. MicroRNAs are short, noncoding nucleotides regulating target messenger RNAs at the post-transcriptional level. MicroRNAs are involved in virtually all biologic processes, including cellular proliferation, apoptosis, and differentiation. Thus, microRNA deregulation often results in impaired cellular function and disease development, so microRNAs have potential therapeutic relevance. Many aspects of the development of essential hypertension at the molecular level are still unknown. The elucidation of these processes regulated by microRNAs and the identification of novel microRNA targets in the pathogenesis of hypertension is a highly valuable and exciting strategy that may eventually led to the development of novel treatment approaches for hypertension. This article reviews the potential role of microRNAs in the mechanisms associated with the development and consequences of hypertension and discusses advances in microRNA-based approaches that may be important in treating hypertension. PMID- 22052338 TI - Long-term nicotine replacement therapy: cancer risk in context. AB - Nicotine replacement therapy (NRT) for up to 12 weeks is well established, safe and efficacious for fostering smoking cessation. Some smokers at a high risk of relapse may benefit from long-term use, and so long-term NRT safety and efficacy have become a paramount question for the FDA and others. Laboratory studies have indicated a carcinogenic potential of nicotine. Animal model studies reported in this issue of the journal by Maier and colleagues (beginning on page 1743) and Murphy and colleagues (beginning on page 1752), however, provide additional reassurance that NRT does not promote lung cancer. Very long-term studies of NRT effects do not yet exist and would be needed to definitively answer the question about NRT efficacy and cancer risk and some decision making will need to be made based on limited human data and experimental studies. The overall NRT safety question is complex and requires consideration of three contexts and comparator groups (long-term NRT/abstinence vs. smoking, long-term intermittent NRT/reduced smoking vs. smoking, and long-term NRT/abstinence vs. abstinence without long term NRT). Although the data on these issues are insufficient, the first comparison seems intuitive and may be compelling enough to allow the FDA to approve a long-term indication for NRT. An important public health goal is to help smokers and their health care providers understand the implications of potential long-term NRT risks in the context of its potential benefits and the far greater risks of continued smoking. PMID- 22052339 TI - How do we safely get people to stop smoking? AB - Nicotine replacement therapy (NRT) is a valuable, proven, and U.S. Food and Drug Administration-approved tool for smoking cessation. However, the discoveries of functional nicotinic acetylcholine receptors (nAChR) on lung epithelial and cancer cells and of nAChR polymorphisms associated with lung cancer risk, in addition to a large number of preclinical studies indicating that nicotine may promote or facilitate cancer development and growth, have prompted concern that NRT, although important for smoking cessation, may actually augment lung carcinogenesis. Therefore, it is of great public health interest that two independent studies reported in this issue of the journal (Murphy and colleagues, beginning on page 1752, and Maier and colleagues, beginning on page 1743) showed that nicotine given in drinking water at a dose to achieve blood concentrations in mice similar to those achieved in people receiving NRT did not enhance lung carcinogenesis or tumor growth in several mouse models of lung cancer. Effective non-nicotine alternatives to NRT, such as varenicline and bupropion, are also available and perhaps better than NRT for smoking cessation therapy. In the near future, nicotine vaccines will likely be added to the smoking cessation armamentarium. However, the normal and pathophysiologic role of nicotine, nAChRs, and the signaling pathways they activate in lung epithelial cells and lung cancer still requires elucidation. PMID- 22052340 TI - Development of low-fat and low-calorie beef sausage using modified starch as fat replacement agent. AB - BACKGROUND: The effects of modified waxy maize starch (MWMS, 10-32.5 g kg(-1)) as a replacement for varying levels of oil or both oil and wheat flour (WF) on the chemical and technological characteristics of 60% beef sausages were investigated. RESULTS: Addition of MWMS increased water-holding capacity and decreased moisture content and both cooking and purge losses. Incorporation of MWMS improved organoleptic acceptance compared with control sausages. CONCLUSION: Sausage formula 5 (F5), containing 20 g kg(-1) MWMS and 50 g kg(-1) WF, was better (P < 0.05) than all other formulae. The total caloric content of the sausages decreased significantly with decreasing fat level (P < 0.05); for example, the decrease in fat content of 57.4% in F5 led to a significant decrease in energy value of 34.9% (P < 0.05). PMID- 22052341 TI - Reduction of molybdate to molybdenum blue by Klebsiella sp. strain hkeem. AB - A novel molybdate-reducing bacterium, tentatively identified as Klebsiella sp. strain hkeem and based on partial 16s rDNA gene sequencing and phylogenetic analysis, has been isolated. Strain hkeem produced 3 times more molybdenum blue than Serratia sp. strain Dr.Y8; the most potent Mo-reducing bacterium isolated to date. Molybdate was optimally reduced to molybdenum blue using 4.5 mM phosphate, 80 mM molybdate and using 1% (w/v) fructose as a carbon source. Molybdate reduction was optimum at 30 degrees C and at pH 7.3. The molybdenum blue produced from cellular reduction exhibited absorption spectrum with a maximum peak at 865 nm and a shoulder at 700 nm. Inhibitors of electron transport system such as antimycin A, rotenone, sodium azide, and potassium cyanide did not inhibit the molybdenum-reducing enzyme. Mercury, silver, and copper at 1 ppm inhibited molybdenum blue formation in whole cells of strain hkeem. PMID- 22052342 TI - Pesticide exposure in farming and forestry and the risk of uveal melanoma. AB - PURPOSE: Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries. METHODS: Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression analyses and adjusted for several potential confounders. RESULTS: 293 case and 3,198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilizers in forestry (OR = 8.93; 95% CI 1.73-42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye color. CONCLUSIONS: Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures. PMID- 22052343 TI - Drop metastases to the pediatric spine revealed with diffusion-weighted MR imaging. AB - Identifying drop metastases to the spine from pediatric brain tumors is crucial to treatment and prognosis. MRI is currently the gold standard for identifying drop metastases, more sensitive than CSF cytology, but imaging is not uncommonly inconclusive. Although diffusion-weighted imaging (DWI) of the brain is very useful in the evaluation of hypercellular tumors, DWI of the spine has not been clinically useful in children because of susceptibility artifacts and lack of spatial resolution. A new technique, readout-segmented echo planar imaging (EPI), has improved these images, allowing for identification of hypercellular drop metastases. We report a case that illustrates the utility of spine DWI in the detection of metastatic disease in children with primary central nervous system (CNS) tumors. This case suggests that DWI of the spine with readout-segmented EPI should be included in the evaluation for drop metastases. PMID- 22052344 TI - Bcl-2/IgH expression in minimal bone marrow infiltration by follicular lymphoma cells. AB - The purpose of this study was to investigate the roles of bcl-2 chromosomal translocation and Bcl-2 protein expression in follicular lymphoma (FL) minimal bone marrow (BM) infiltration. We identified the same bcl-2/IgH fusion gene in paraffin-embedded lymph node (LN) samples and BM samples using immunohistochemistry (IHC), immunocytochemistry (ICC), cytologic morphology and fluorescence in situ hybridization (FISH). The presence of the Bcl-2/IgH fusion gene in the BM samples and paraffin-embedded LN samples from 56 patients with follicular lymphomas was detected using FISH. The Bcl-2 protein levels in BM and paraffin-embedded tissues were quantified using ICC and IHC, respectively. Approximately 78.6% (44/56) of the paraffin-embedded LN tissue sections that underwent FISH analysis had a bcl-2/IgH translocation. The primary lesion was also positive for the bcl-2/IgH fusion gene, as were the BM minimal infiltrates. The bcl-2/IgH rearrangement occurred in 88.6% (39/44) of the BM specimens. The bcl-2/IgH recombination rate in stage III/IV cancers was significantly different to that observed in stage I/II cancers (p=0.041). In 59% (23/39) of the cases with t(14;18), Bcl-2 was found to be present as assessed by ICC. Positive Bcl-2 ICC staining and the t(14;18) translocation (as detected using FISH) were positively correlated (p=0.028). We then applied the FISH method to slides that had previously been morphologically evaluated using Wright-Giemsa staining; any slides with at least one abnormal cell were subjected to FISH analysis following staining. The assessment of bcl-2/IgH translocation status may contribute to the better detection of minimal BM infiltration by FL cells. Utilizing FISH and cytologic morphology techniques allows for earlier and more accessible BM examination. PMID- 22052346 TI - Are prions part of the dark matter of the cell? AB - The [PSI+] determinant in Saccharomyces cerevisiae is the prion protein corresponding to the eRF3 translation termination factor. Numerous infectious proteins have been described in yeast, in comparison of the unique PrP protein in higher eukaryotes. The presence of the PrP prion is associated with mammalian diseases. Whether fungal prions are beneficial or deleterious are still under discussions. The review focuses on [PSI+]-induced phenotypes and the resulting physiological consequences to shed light on the cellular changes occurring in a [PSI+] cell and its possible role in nature. To date, only two genes directly regulated at the translational level by [PSI+] have been identified. Yet, through all the published works, obtaining a consensus for the described [PSI+] phenotypes appeared a tricky task. They are highly dependent on the prion variant and the genetic background of the strain. The [PSI+] prion might generate diverse modifications not only at the translational, but also at the transcriptional levels, and the phenotypic heterogeneity is the result of these complex combinations of the genotypic expression. PMID- 22052347 TI - The [RNQ+] prion: a model of both functional and pathological amyloid. AB - The formation of fibrillar amyloid is most often associated with protein conformational disorders such as prion diseases, Alzheimer disease and Huntington disease. Interestingly, however, an increasing number of studies suggest that amyloid structures can sometimes play a functional role in normal biology. Several proteins form self-propagating amyloids called prions in the budding yeast Saccharomyces cerevisiae. These unique elements operate by creating a reversible, epigenetic change in phenotype. While the function of the non-prion conformation of the Rnq1 protein is unclear, the prion form, [RNQ+], acts to facilitate the de novo formation of other prions to influence cellular phenotypes. The [RNQ+] prion itself does not adversely affect the growth of yeast, but the overexpression of Rnq1p can form toxic aggregated structures that are not necessarily prions. The [RNQ+] prion is also involved in dictating the aggregation and toxicity of polyglutamine proteins ectopically expressed in yeast. Thus, the [RNQ+] prion provides a tractable model that has the potential to reveal significant insight into the factors that dictate how amyloid structures are initiated and propagated in both physiological and pathological contexts. PMID- 22052348 TI - Polyglutamine misfolding in yeast: toxic and protective aggregation. AB - Protein misfolding is associated with many human diseases, including neurodegenerative diseases, such as Alzheimer disease, Parkinson disease and Huntington disease. Protein misfolding often results in the formation of intracellular or extracellular inclusions or aggregates. Even though deciphering the role of these aggregates has been the object of intense research activity, their role in protein misfolding diseases is unclear. Here, I discuss the implications of studies on polyglutamine aggregation and toxicity in yeast and other model organisms. These studies provide an excellent experimental and conceptual paradigm that contributes to understanding the differences between toxic and protective trajectories of protein misfolding. Future studies like the ones discussed here have the potential to transform basic concepts of protein misfolding in human diseases and may thus help to identify new therapeutic strategies for their treatment. PMID- 22052349 TI - Yeast prions assembly and propagation: contributions of the prion and non-prion moieties and the nature of assemblies. AB - Yeast prions are self-perpetuating protein aggregates that are at the origin of heritable and transmissible non-Mendelian phenotypic traits. Among these, [PSI+], [URE3] and [PIN+] are the most well documented prions and arise from the assembly of Sup35p, Ure2p and Rnq1p, respectively, into insoluble fibrillar assemblies. Fibril assembly depends on the presence of N- or C-terminal prion domains (PrDs) which are not homologous in sequence but share unusual amino-acid compositions, such as enrichment in polar residues (glutamines and asparagines) or the presence of oligopeptide repeats. Purified PrDs form amyloid fibrils that can convert prion-free cells to the prion state upon transformation. Nonetheless, isolated PrDs and full-length prion proteins have different aggregation, structural and infectious properties. In addition, mutations in the "non-prion" domains (non PrDs) of Sup35p, Ure2p and Rnq1p were shown to affect their prion properties in vitro and in vivo. Despite these evidences, the implication of the functional non PrDs in fibril assembly and prion propagation has been mostly overlooked. In this review, we discuss the contribution of non-PrDs to prion assemblies, and the structure-function relationship in prion infectivity in the light of recent findings on Sup35p and Ure2p assembly into infectious fibrils from our laboratory and others. PMID- 22052351 TI - Strategies for identifying new prions in yeast. AB - The unexpected discovery of two prions, [URE3] and [PSI+], in Saccharomyces cerevisiae led to questions about how many other proteins could undergo similar prion-based structural conversions. However, [URE3] and [PSI+] were discovered by serendipity in genetic screens. Cataloging the full range of prions in yeast or in other organisms will therefore require more systematic search methods. Taking advantage of some of the unique features of prions, various researchers have developed bioinformatic and experimental methods for identifying novel prion proteins. These methods have generated long lists of prion candidates. The systematic testing of some of these prion candidates has led to notable successes; however, even in yeast, where rapid growth rate and ease of genetic manipulation aid in testing for prion activity, such candidate testing is laborious. Development of better methods to winnow the field of prion candidates will greatly aid in the discovery of new prions, both in yeast and in other organisms, and help us to better understand the role of prions in biology. PMID- 22052350 TI - Modeling Huntington disease in yeast: perspectives and future directions. AB - Yeast have been extensively used to model aspects of protein folding diseases, yielding novel mechanistic insights and identifying promising candidate therapeutic targets. In particular, the neurodegenerative disorder Huntington disease (HD), which is caused by the abnormal expansion of a polyglutamine tract in the huntingtin (htt) protein, has been widely studied in yeast. This work has led to the identification of several promising therapeutic targets and compounds that have been validated in mammalian cells, Drosophila and rodent models of HD. Here we discuss the development of yeast models of mutant htt toxicity and misfolding, as well as the mechanistic insights gleaned from this simple model. The role of yeast prions in the toxicity/misfolding of mutant htt is also highlighted. Furthermore, we provide an overview of the application of HD yeast models in both genetic and chemical screens, and the fruitful results obtained from these approaches. Finally, we discuss the future of yeast in neurodegenerative research, in the context of HD and other diseases. PMID- 22052352 TI - Modulation and elimination of yeast prions by protein chaperones and co chaperones. AB - The yeast system has provided considerable insight into the biology of amyloid and prions. Here we focus on how alterations in abundance or function of protein chaperones and co-chaperones affect propagation of yeast prions. In spite of a considerable amount of information, a clear understanding of the molecular mechanisms underlying these effects remains wanting. PMID- 22052355 TI - Detection of anti-Leptospira antibodies in captive nonhuman primates from Salvador, Brazil. AB - Leptospirosis is a widely distributed zoonosis that affects several species of domestic and wild animals. Under captive conditions, Leptospirosis is a potential problem because the physical conditions in most zoos and research centers cannot prevent the captive animals from being exposed to rodents, raccoons, opossums, and other local wildlife that are known carriers. Yet, despite the potential risk, animals that are destined for reintroduction into the wild are not routinely tested for anti-Leptospira antibodies before their release. The purpose of this study was to determine the occurrence of anti-Leptospira antibodies in captive New World monkeys that were housed in the Wild Animals Screening Center in Salvador, Brazil. Blood samples were collected from 44 monkeys (28 Callithrix jacchus, eight Callithrix pennicilata, and eight Cebus sp.). The animals were screened for antibodies with the microscopic agglutination test. Twenty-five (56.8%) primates were seroreactive, with Icterohaemorrhagiae being the most frequent serogroup. None of the monkeys, however, presented clinical signs of leptospirosis. Thus, seroreactivity with low titers in asymptomatic animals, as observed in this study, suggests exposure to the agent. The unexpected predominance of the serogroup Icterohaemorrhagiae further suggests that exposure to this serogroup occurred in captivity. Therefore, the dangerous possibility cannot be ignored that reintroduced monkeys will carry the leptospiral serovars into wild populations. In conclusion, primates exposed to urban serovars before their release from captivity represent a potentially significant health risk to wild populations. PMID- 22052353 TI - The yeast prions [PSI+] and [URE3] are molecular degenerative diseases. AB - The yeast prions [URE3] and [PSI] are not found in wild strains, suggesting they are not an advantage. Prion-forming ability is not conserved, even within Saccharomyces, suggesting it is a disease. Prion domains have non-prion functions, explaining some conservation of sequence. However, in spite of the sequence being constrained in evolution by these non-prion functions, the prion domains vary more rapidly than the remainder of the molecule, and these changes produce a transmission barrier, suggesting that these changes were selected to block prion infection. Yeast prions [PSI] and [URE3] induce a cellular stress response (Hsp104 and Hsp70 induction), suggesting the cells are not happy about being infected. Recently, we showed that the array of [PSI] and [URE3] prions includes a majority of lethal or very toxic variants, a result not expected if either prion were an adaptive cellular response to stress. PMID- 22052354 TI - Modeling ALS and FTLD proteinopathies in yeast: an efficient approach for studying protein aggregation and toxicity. AB - In recent years there have been several reports of human neurodegenerative diseases that involve protein misfolding being modeled in the yeast Saccharomyces cerevisiae. This review summarizes recent advances in understanding the specific mechanisms underlying intracellular neuronal pathology during Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD), including SOD1, TDP 43 and FUS protein inclusions and the potential of these proteins to be involved in pathogenic prion-like mechanisms. More specifically, we focus on findings from yeast systems that offer tremendous possibilities for screening for genetic and chemical modifiers of disease-related proteotoxicity. PMID- 22052356 TI - Number of screens for overdetection as an indicator of absolute risk of overdiagnosis in prostate cancer screening. AB - As with wide-spread use of prostate cancer (Pca) screening with prostate-specific antigen testing, overdetection has increasingly gained attention. The authors aimed to estimate absolute risk of overdetection (RO) in Pca screening with various interscreening intervals and ages at start of screening. We estimated age specific preclinical incidence rates (per 100,000 person-years) for progressive cancer (from 128 for age group 55-58 years to 774 for age group 67-71 years) and nonprogressive cancer (from 40 for age group 55-58 years to 66 for age group 67 71 years), the mean sojourn time (7.72 years) and the sensitivity (42.8% at first screen and 59.8% at the second screen) by using a multistep epidemiological model with data from the Finnish randomized controlled trial. The overall number of screens for overdetection (NSO) was 29 (95% confidence interval (CI): 18, 48) for screenees aged 55-67 years, equivalent to 3.4 (95% CI: 2.1, 5.7) overdetected Pcas per 100 screenees. The NSO decreased from 63 (95% CI: 37, 109) at the first screen to 29 (95% CI: 18, 48) at the third screen and from 43 (95% CI: 36, 52) for age 55 years to 25 (95% CI: 8, 75) at age 67 years at the first screen. In conclusion, around 3.4 cases for every 100 screened men would be overdetected during three screen rounds (~ 13 years of follow-up) in the Finnish randomized controlled trial. Elucidating the absolute RO under various scenarios makes contribution for evaluating the benefit and harm of Pca screening. PMID- 22052357 TI - mTOR-regulated senescence and autophagy during reprogramming of somatic cells to pluripotency: a roadmap from energy metabolism to stem cell renewal and aging. AB - Molecular controllers of the number and function of tissue stem cells may share common regulatory pathways for the nuclear reprogramming of somatic cells to become induced Pluripotent Stem Cells (iPSCs). If this hypothesis is true, testing the ability of longevity-promoting chemicals to improve reprogramming efficiency may provide a proof-of-concept validation tool for pivotal housekeeping pathways that limit the numerical and/or functional decline of adult stem cells. Reprogramming is a slow, stochastic process due to the complex and apparently unrelated cellular processes that are involved. First, forced expression of the Yamanaka cocktail of stemness factors, OSKM, is a stressful process that activates apoptosis and cellular senescence, which are the two primary barriers to cancer development and somatic reprogramming. Second, the a priori energetic infrastructure of somatic cells appears to be a crucial stochastic feature for optimal successful routing to pluripotency. If longevity promoting compounds can ablate the drivers and effectors of cellular senescence while concurrently enhancing a bioenergetic shift from somatic oxidative mitochondria toward an alternative ATP-generating glycolytic metabotype, they could maximize the efficiency of somatic reprogramming to pluripotency. Support for this hypothesis is evidenced by recent findings that well-characterized mTOR inhibitors and autophagy activators (e.g., PP242, rapamycin and resveratrol) notably improve the speed and efficiency of iPSC generation. This article reviews the existing research evidence that the most established mTOR inhibitors can notably decelerate the cellular senescence that is imposed by DNA damage-like responses, which are somewhat equivalent to the responses caused by reprogramming factors. These data suggest that fine-tuning mTOR signaling can impact mitochondrial dynamics to segregate mitochondria that are destined for clearance through autophagy, which results in the loss of mitochondrial function and in the accelerated onset of the glycolytic metabolism that is required to fuel reprogramming. By critically exploring how mTOR-regulated senescence, bioenergetic infrastructure and autophagy can actively drive the reprogramming of somatic cells to pluripotency, we define a metabolic roadmap that may be helpful for designing pharmacological and behavioral interventions to prevent or retard the dysfunction/exhaustion of aging stem cell populations. PMID- 22052358 TI - Caveolin-1: a new therapeutic target in tissue fibrosis and scleroderma? PMID- 22052359 TI - Outcome of the p53-mediated DNA damage response in neuroblastoma is determined by morphological subtype and MYCN expression. AB - BACKGROUND: MYCN oncogene amplification occurs in 20-25% of neuroblastoma and is associated with a poor prognosis. We previously reported that MYCN amplified (MNA) p53 wild-type neuroblastoma cell lines failed to G1 arrest in response to irradiation, but this could not be attributed to MYCN alone. HYPOTHESIS: Genes co amplified with MYCN and/or the predominant cell type, neuronal (N) or substrate adherent (S) phenotypes determine the downstream response to DNA damage in neuroblastoma cell lines. METHODS: The MYCN amplicons of five MNA and two non-MNA cell line were mapped using 50K Single Nucleotide Polymorphism (SNP) arrays. One MNA (NBL-W) and one non-MNA neuroblastoma cell line (SKNSH) were sub-cloned into N and S-type cells and the p53 pathway investigated after irradiation induced DNA damage. To determine the role of p53 it was knocked down using siRNA. RESULTS: No genes with a potential role in cell cycle regulation were consistently co amplified in the MNA cell lines studied. High MYCN expressing NBLW-N cells failed to G1 arrest following irradiation and showed impaired induction of p21 and MDM2, whereas low MYCN expressing NBLW-S cells underwent a G1 arrest with induction of p21 and MDM2. Conversely N type cells underwent higher levels of apoptosis than S type cells. Following p53 knockdown in SHSY5Y N-type cells there was a decrease in apoptosis. CONCLUSIONS: The downstream response to DNA damage in p53 wild-type neuroblastoma cell lines is p53 dependent, and determined both by the morphological sub-type and MYCN expression. PMID- 22052360 TI - Good practice in antibiotic use: what about linezolid in a French university hospital? AB - OBJECTIVE: Linezolid represents an important advance in the treatment of methicillinresistant staphylococci. Its effectiveness should be preserved by appropriate uses. The aims of this survey were to describe the use of linezolid in clinical practice and to assess its overall safety. METHODS: This retrospective observational study included patients treated with linezolid in 2008 in all departments at the CHU Nantes. A data-collection card was completed using the patients' medical files. RESULTS: A total of 179 patients from 23 different departments were included. Fifty-four per cent of indications were outside the Marketing Authorization criteria, and were mainly osteoarticular infections and septicaemia (22% and 8% of total prescriptions, respectively). Inefficacy of first-line antibiotic treatment (23%) and alterations in renal function (23%) were the main reasons for using linezolid, which was prescribed as a first-line therapy in 28% of patients. Fifty-three per cent of infections were documented microbiologically, of which 58% were due to a methicillin-resistant Staphylococcus. CONCLUSIONS: Linezolid seems to be a possible therapeutic strategy in case of multiresistant bacteria and/or complex clinical situations. Because many prescriptions fall outside the Marketing Authorization criteria, this study highlights the need to have clinical data available for such situations. PMID- 22052361 TI - Pseudomeningoceles of the sphenoid sinus masquerading as sinus pathology. AB - OBJECTIVES/HYPOTHESIS: To describe the clinical presentation, pathophysiology, and treatment of spontaneous cerebrospinal fluid (CSF) leaks of the sphenoid bone, with an emphasis on a previously undescribed form in this location, in which CSF is trapped under the mucosa of the sinonasal cavity or in the soft tissue of the skull base. STUDY DESIGN: Case series and literature review. METHODS: Analysis of cases through medical records and literature review. RESULTS: Four examples of unusual spontaneous CSF leaks of the skull base are presented. In each case, a CSF collection was contained behind the sinonasal mucosa of the sphenoid sinus, resembling a nasal polyp or mucocele on exam or imaging. In one case, the fluid collection was also associated with significant bone resorption and extravasation into the soft tissue of the infratemporal fossa. In each case, small defects of the ventral skull base (sphenoid bone) were the source of the CSF leaks. Successful treatment was achieved after transnasal endoscopic repair of the skull base defects using a combination of free abdominal fat grafts, free fascial grafts, and pedicled nasoseptal flaps. Postoperatively, a ventriculoperitoneal shunt was placed if the intracranial pressure was elevated. CONCLUSIONS: Spontaneous CSF leaks arising in the sphenoid sinus may not always present with overt CSF rhinorrhea but with a submucosal fluid collection (pseudomeningocele) that may mimic a mucocele or nasal polyp. These bona fide pseudomeningoceles of the skull base may be associated with elevated intracranial pressure and can be managed using endoscopic endonasal surgery. PMID- 22052362 TI - Metabolism studies of a small-molecule tumor necrosis factor-alpha (TNF-alpha) inhibitor, UTL-5b (GBL-5b). AB - UTL-5b is an anti-inflammatory and anti-arthritic small-molecule tumor necrosis factor-alpha inhibitor and a structural analogue of the anti-arthritic drug, leflunomide. Leflunomide is known to be metabolized to teriflunomide, but the metabolites of UTL-5b have not been reported. The objective of this study was to investigate whether UTL-5b has a similar metabolic behavior as leflunomide. Preliminary studies showed that when exposed to microsomes in vitro with or without NADPH, UTL-5b disappeared within 30 min. To further investigate the microsomal metabolism, liquid chromatography-ultraviolet (LC-UV) and LC/tandem mass spectrometry (LC-MS/MS) were employed to, respectively, monitor the microsomal metabolites and identify the structure of the metabolites using LC full scan MS and LC combined with multiple-ion monitoring MS. Fragmentation determination was analyzed by two types of scans: product ion scans and precursor ion scan. The in vitro microsomal treatment of UTL-5b resulted in two major metabolites: 5-methylisoxazole-3-carboxylic acid and 2-chloroaniline. Thus, the in vitro metabolic behavior of UTL-5b appears to be different from that of leflunomide in that the isoxazole ring is cleaved. PMID- 22052363 TI - Simultaneous T1 measurements and proton resonance frequency shift based thermometry using variable flip angles. AB - A method is presented which allows precise temperature and longitudinal (T(1)) relaxation time measurements with high spatial and temporal resolution. This is achieved by combining dynamic variable flip angle based T(1) relaxation mapping with proton resonance frequency shift based thermometry. Herein, dynamic T(1) mapping is either used as a complementary measure of temperature or for the detection of T(1) contrast agent release. For the first application, the temperature evolution during a high-intensity focused ultrasound tissue ablation experiment was measured in both, porcine fat and muscle, simultaneously. In this application, temperature accuracies of 2.5 K for T(1)-based thermometry in fat and 1.2 K for proton resonance frequency shift-based thermometry in muscle were observed. The second application relates to MR-guidance of high-intensity focused ultrasound-induced local drug delivery by means of thermo-sensitive liposomes labeled with a T(1) contrast agent (Gd-HPDO3A). When the measured temperature exceeded the phase transition temperature of the liposomes, T(1) was observed to decrease with a good temporal and spatial correlation due to the release of Gd HPDO3A. The presented results demonstrate the feasibility of the proposed method for two important applications in MR-guided noninvasive therapy. It offers a high temporal resolution when compared with interleaved Look-Locker based T(1) mapping techniques and thus represents an interesting candidate for simultaneous real time monitoring of T(1) and temperature changes. PMID- 22052364 TI - Structural changes of the sediment bacterial community in Meiliang Bay of Lake Taihu, China, during typhoon Morakot, 2009. AB - We investigated changes in bacterial communities of the sediment in a large, shallow, eutrophic, freshwater Lake Taihu, China, during typhoon Morakot (August 7 to 13, 2009). Based on cluster analysis of the DGGE banding patterns, bacterial communities in different sediment samples were very similar to each other. However, samples from the middle period of the typhoon were different from those of the early and late periods of the typhoon. Two bacterial groups, Bacteroidetes and Nitrospirae, rapidly appeared or increased in the sediment samples of the middle period of the typhoon, due to the strong turbulence in the water column caused by typhoon resulted in the exchange of surface sediment with a high level of organic matter with the water column, and severe disturbance to the anaerobic layer of the sediments. Redundancy analysis showed that organic matter contributed significantly to the changes in sediment bacterial communities during the typhoon. Our study demonstrated that the response of sediment bacterial communities to the typhoon event was very rapid but of short duration. PMID- 22052365 TI - Cancer drug safety presents challenges: oncologists, researchers, and government balance risks with benefits. PMID- 22052366 TI - FDA implements new initiatives to ensure drug safety. PMID- 22052367 TI - Bevacizumab recommendation highlights difficulties. PMID- 22052369 TI - Chondroitin sulphate enhances the antitumor activity of gemcitabine and mitomycin C in bladder cancer cells with different mechanisms. AB - Non-muscle invasive bladder cancer is the most common type of bladder cancer in Western countries. The glycosaminoglycan (GAG) layer at the bladder surface non specifically blocks the adherence of bacteria, ions and molecules to the bladder epithelium and bladder cancer cells express CD44 that binds GAG. Currently, there are few options other than cystectomy for the management of non-muscle invasive bladder cancer with intravesical chemotherapy using several drugs such as gemcitabine (GEM) and mitomycin-C (MMC) with poor prophylactic activity. In this study, we investigated the effects of the GAG chondroitin sulphate (CS) on the growth inhibition of human bladder cancer cell lines HT-1376 and effects of the combination between GEM or MMC with CS. We have found that CS, MMC and GEM induced 50% growth inhibition at 72 h. Therefore, we have evaluated the growth inhibition induced by different concentration of CS in combination with MMC or GEM, respectively, at 72 h. We have observed, at Calcusyn analysis, a synergism when HT-1376 cells were treated with CS in combination with MMC or GEM, respectively, if used at an equimolar ratio. We have also found that CS/GEM combination induced a strong potentiation of apoptosis with the consequent activation of caspases 9 and 3. On the other hand, HT-1376 cells were necrotic if exposed to the CS/MMC combination and no signs of caspase activation was observed. In conclusion, in the human bladder cancer cell line HT-1376 pharmacological combination of CS with GEM or MMC resulted in a strong synergism on cell growth inhibition. PMID- 22052370 TI - Response of induced perturbation on replicating beta-proteobacterial ammonia oxidizing populations in soil. AB - The short-term response of induced perturbation by 4-ethylphenol on beta proteobacterial ammonia oxidizers (beta-AOB) was investigated in two soils with initial differences in community structure. The hypotheses were that short-term effects of a disturbance of the AOB community is best monitored by specifically looking at the active populations and that soils with dissimilar active AOB populations would display different degree of resistance or resilience. Two soils from a previously characterized long-term field study fertilized with manure or sewage sludge was used. Soil microcosms were incubated in the laboratory over 15 days. The substrate-induced ammonia oxidation was measured, and the composition of beta-AOB communities was determined by PCR-DGGE of specific beta-AOB 16S rRNA gene fragments. Actively replicating members of the beta-AOB were distinguished by the use of bromodeoxyuridine (BrdU) immunocapture. This approach demonstrated that only a minor fraction of the total AOB community was active. Exposure to 4 ethylphenol resulted in approximately 90% lowered substrate-induced ammonia oxidation rates in both soils. This activity inhibition was not accompanied by shifts in beta-AOB community structure when total beta-AOB DNA was studied. By contrast, changes were seen in the DGGE banding pattern of the BrdU-labeled community DNA after 4-ethylphenol addition in the manure-fertilized soil. In the sewage sludge fertilized soil, the banding pattern of the BrdU-labeled beta-AOB remained unchanged, but bands were weaker after the disturbance. In conclusion, it was shown that BrdU immunocapture was applicable to detect shifts in community composition among replicating beta-AOB populations in soil. However, this was not reflected by the soils' ammonia oxidation capacity to resist to or recover from the induced perturbation suggesting that rapid population shifts may not influence soil functioning in a short-term perspective. PMID- 22052372 TI - Visinin-like protein-1 overexpression is an indicator of lymph node metastasis and poor prognosis in colorectal cancer patients. AB - Lymph node metastasis is an important factor determining outcome from colorectal cancer (CRC). Identification of molecular markers useful to predict lymph node metastasis is urgently needed. Our objective was to identify genes useful for characterization and prediction of lymph node metastasis in CRC. Gene expression profiles of cancer were determined by human U133 Plus 2.0 GeneChip(r) in 24 CRC patients, and patients with and without lymph node metastasis were compared. We focused on the visinin-like protein-1 (VSNL-1) gene and evaluated VSNL-1 mRNA expression levels with reverse transcriptase-polymerase chain reaction and immunohistochemical methods. Immunohistochemical evaluation of VSNL-1 mRNA expression was also performed in 143 other CRC patients to determine clinicopathological significance of VSNL-1. Twenty-four novel discriminating genes showed expression significantly different between patients with and without lymph node metastasis. Mean level of VSNL-1 mRNA expression in tumor tissue with lymph node metastasis was significantly higher than that in tissue without lymph node metastasis. Immunohistochemical examination demonstrated immunoreactivity for VSNL-1 in cytoplasm of the cancer cells with lymph node metastasis. High VSNL 1 expression was significantly associated with lymphatic invasion in stage II disease (p = 0.0061) and number of lymph node metastases in stage III disease (p = 0.0461). Patients with high VSNL-1 expression had significantly poorer prognosis than those with low expression in stage III disease (p = 0.045). This study is the first to demonstrate a prognostic role for VSNL-1 at the mRNA level, suggesting the possible usefulness of VSNL-1 as a predictor of lymph node metastasis and poor prognosis in CRC. PMID- 22052373 TI - Polymorphism of the aryl-hydrocarbon receptor gene in intron 10 of human cancers. AB - Polychlorinated dibenzo-p-dioxins (PCDDs) and related halogenated aromatic hydrocarbons (e.g., PCDFs), often called "dioxins", are ubiquitously present environmental contaminants. Some of them, notably 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD), are among the most toxic synthetic compounds known. The biological effects of dioxins are mediated via the aryl hydrocarbon receptor (AhR). Mutations in the AhR transactivation domain are linked to sensitivity to the acute lethality of TCDD. We present here a study of AhR gene polymorphism in normal and cancer human tissues affecting pre-mRNA splicing in the AhR gene coding transactivation domain region (exon 10, intron 10, exon 11 region), previously shown to be associated with AhR dysfunction. We tested 126 pairs of normal and cancer tissue samples from liver, lung, stomach, kidney, mucous, breast, and pancreas of 49 males and 77 females (45-70 years of age). We used in vitro splicing assay, RT-PCR and sequencing methods. Our results showed that in an in vitro system it is possible to reconstitute cellular pre-mRNA splicing events. Tested cancer tissues did not contain mutations in the AhR transactivation domain region when the DNA sequences were compared with those from normal tissues. There were also no differences in AhR mRNA splice variants between normal and malignant breast tissues and no polymorphisms in the studied regions or cDNA. PMID- 22052374 TI - Body composition measures of obese adolescents by the deuterium oxide dilution method and by bioelectrical impedance. AB - The objectives of the present study were to describe and compare the body composition variables determined by bioelectrical impedance (BIA) and the deuterium dilution method (DDM), to identify possible correlations and agreement between the two methods, and to construct a linear regression model including anthropometric measures. Obese adolescents were evaluated by anthropometric measures, and body composition was assessed by BIA and DDM. Forty obese adolescents were included in the study. Comparison of the mean values for the following variables: fat body mass (FM; kg), fat-free mass (FFM; kg), and total body water (TBW; %) determined by DDM and by BIA revealed significant differences. BIA overestimated FFM and TBW and underestimated FM. When compared with data provided by DDM, the BIA data presented a significant correlation with FFM (r = 0.89; P < 0.001), FM (r = 0.93; P < 0.001) and TBW (r = 0.62; P < 0.001). The Bland-Altman plot showed no agreement for FFM, FM or TBW between data provided by BIA and DDM. The linear regression models proposed in our study with respect to FFM, FM, and TBW were well adjusted. FFM obtained by DDM = 0.842 x FFM obtained by BIA. FM obtained by DDM = 0.855 x FM obtained by BIA + 0.152 x weight (kg). TBW obtained by DDM = 0.813 x TBW obtained by BIA. The body composition results of obese adolescents determined by DDM can be predicted by using the measures provided by BIA through a regression equation. PMID- 22052375 TI - Antiretroviral therapy-associated dyslipidemia in patients from a reference center in Brazil. AB - The aim of this study was to determine the impact of antiretroviral therapy on the lipid profile of human immunodeficiency virus (HIV) patients before and after the initiation of highly active antiretroviral therapy (HAART). This was a cross sectional analysis of patients receiving HAART at a reference center in Belo Horizonte, Brazil, on the basis of medical records from 2002 to 2006. Patients were included if they had at least one lipid test or a clinical or laboratory diagnosis of dyslipidemia/lipodystrophy. Among the 692 patients, 620 met the eligibility criteria. The majority were males (66.5%), middle age (average 39 years), had a low educational level (60.4%), and low income (51.0%). HAART duration ranged from 11 days to 4.6 years, with a mean of 28.6 months (SD = +/- 470.19 days). The prevalence of dyslipidemia/lipodystrophy nearly tripled (11.3% pre- and 32.4% post-HAART). Dyslipidemia was associated with older age (P = 0.007), nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI) regimens (P = 0.04), NRTI + non-NRTI (NNRTI) regimens (P = 0.026), the use of stavudine (d4T) in any regimen (P = 0.002) or in NRTI-based regimens (P = 0.006), and longer exposure to HAART (P < 0.000). In addition, there was no correlation between dyslipidemia and gender (P = 0.084). Only 2.0% of the patients received treatment for dyslipidemia during the trial. These results show a need for continuous monitoring of patients under antiretroviral therapy, particularly those using NRTI-based regimens, especially when combined with d4T and PIs. Secondly, interventions should be developed to correct metabolic changes. PMID- 22052376 TI - The pleiotropic effects of statins in the prevention of atherosclerosis : Editorial to: "Simvastatin suppresses apoptosis in vulnerable atherosclerotic plaques through regulating the expression of p53, Bcl-2 en Bcl-xL" by Weiwei Qin et al. PMID- 22052378 TI - Simian varicella virus gene expression during acute and latent infection of rhesus macaques. AB - Varicella zoster virus (VZV) is a neurotropic alpha-herpesvirus that causes chickenpox during primary infection and establishes latency in sensory ganglia. Reactivation of VZV results in herpes zoster and other neurological complications. Our understanding of the VZV transcriptome during acute and latent infection in immune competent individuals remains incomplete. Infection of rhesus macaques with the homologous simian varicella virus (SVV) recapitulates the hallmarks of VZV infection. We therefore characterized the SVV transcriptome by quantitative real-time reverse transcriptase PCR during acute infection in bronchial alveolar lavage (BAL) cells and peripheral blood mononuclear cells, and during latency in sensory ganglia obtained from the same rhesus macaques. During acute infection, all known SVV open reading frames (ORFs) were detected, and the most abundantly expressed ORFs are involved in virus replication and assembly such as the transcriptional activator ORF 63 and the structural proteins ORF 41 and ORF 49. In contrast, latent SVV gene expression is highly restricted. ORF 61, a viral transactivator and latency-associated transcript, is the most prevalent transcript detected in sensory ganglia. We also detected ORFs A, B, 4, 10, 63, 64, 65, 66, and 68 though significantly less frequently than ORF 61. This comprehensive analysis has revealed genes that potentially play a role in the establishment and/or maintenance of SVV latency. PMID- 22052379 TI - Checkpoints in productive and latent infections with herpes simplex virus 1: conceptualization of the issues. AB - The fundamental question posed here is why in dorsal root ganglia herpes simplex viruses (HSV) can establish a silent infection in which only latency associate transcripts (LAT) and miRNAs are expressed and the neuronal cell survives whereas in non-neuronal cells HSV replicates and destroys the infected cells. Current evidence indicates that in productive infection there are two checkpoints. The first is at activation of alpha genes and requires a viral protein (VP16) that recruits HCF-1, Oct1, LSD1, and the CLOCK histone acetyl transferase to demethylate histones and initiate transcription. The second checkpoint involves activation of beta and gamma genes. An alpha protein, ICP0, activates transcription by displacing HDAC1 or 2 from the HDAC/CoREST/LSD1/REST repressor complex at its DNA binding sites. Current data suggest that in dorsal root ganglia VP16 and HCF-1 are not translocated to neuronal nucleus and that the HDAC/CoREST/LSD1/REST complex is not suppressed-a first step in silencing of the viral genome and establishment of heterochromatin. The viral genome remains in a state of equilibrium with respect to viral gene expression. The function of both LAT and the micro RNAs is to silence low level expression of viral genes that could reactivate the latent genomes. PMID- 22052380 TI - Effect of exogenous administration of Candida albicans autoregulatory alcohols in a murine model of hematogenously disseminated candidiasis. AB - Candida albicans supernatants contain a mixture of autoregulatory alcohols. In vitro, when added individually or in combination, these alcohols inhibit the yeast to filamentous form conversion. Here we evaluate the in vivo effect of the exogenous administration of a Cocktail solution simulating the composition of alcohols present in a C. albicans culture supernatant (1 ml; 94 MUmol l(-1) isoamyl alcohol, 70 MUmol l(-1) 2-phenylethanol, 3.2 n mol l(-1) E -nerolidol, and 18 n mol l(-1) E,E -farnesol) using the well established murine model of hematogenously disseminated candidiasis. Mice injected intraperitoneally with the Cocktail solution demonstrated increased survival and decreased organ fungal burden compared to control mice. Histological observations suggest that the Cocktail, to some extent, has an inhibitory effect on cell filamentation within the kidney. These findings suggest that the exogenous administration of C. albicans autoregulatory alcohols displays a protective effect during disseminated candidiasis. PMID- 22052381 TI - New and old NMR experiments for the resonance assignment of complex oligosaccharides--application to a cyclodextrin derivative. AB - The complete assignment of the (1)H and (13)C sugar resonances in mono-3,6 anhydro-heptakis(2,3-O-methyl)-hexakis(6-O-methyl)-beta-cyclodextrin, an asymmetrically functionalized beta-cyclodextrin, was carried out by means of 2D NMR experiments. The TOCSY and the homonuclear multiple relay COSY spectra provided most of the (1)H assignments. The multiplicity edited HSQC and a set of F(1) selective HSQC-TOCSY and multiple relay HSQC-COSY spectra gave access to most of the (13)C chemical shifts. The latter were fully and accurately determined by means of a pair of complementary, highly folded HSQC-TOCSY spectra. The TOCSY-ROESY and ROESY-TOCSY spectra yielded the sequential assignment of the sugar units. A high resolution F(1) selective F(1) decoupled version of the TOCSY ROESY experiment was recorded. PMID- 22052382 TI - Alzheimer's disease clinical trials: changing the paradigm. PMID- 22052383 TI - Bipolar depression: an evidence-based approach. AB - Bipolar disorder is a complex, multidimensional illness that is often difficult to treat. Unfortunately, bipolar patients are much more likely to experience depression, which is all too often severe and a potentially lethal phase of the illness. In addition, pharmacotherapies with strong evidence for bipolar depression are limited. Most treatments are based on unsupported extrapolation from the treatment of unipolar depression or are derived largely from the clinical practice experience. In this article, we focus on the treatment of bipolar depression, with particular focus on evidence from the existing literature, to help guide readers in clinical practice. PMID- 22052384 TI - First-trimester bleeding characteristics associate with increased risk of preterm birth: data from a prospective pregnancy cohort. AB - BACKGROUND: Prior evidence linking first-trimester bleeding with preterm birth (PTB, <37 weeks gestation) risk has been inconsistent and may be biased by subject selection and/or incomplete documentation of bleeding episodes for all participants. Prior studies have not carefully examined the role of bleeding characteristics in PTB risk. In the present study, we estimate the association between first-trimester bleeding and PTB in a non-clinical prospective cohort and test whether bleeding characteristics better predict risk. METHODS: Women were enrolled in Right from the Start (2000-2009), a prospective pregnancy cohort. Data about bleeding and bleeding characteristics were examined with logistic regression to assess association with PTB. RESULTS: Among 3978 pregnancies 344 were PTB and 3634 term. Bleeding was reported by 986 (26%) participants. After screening candidate confounders, only multiple gestations remained in the model. Bleeding associated with PTB [odds ratio (OR)(adjusted) = 1.40, 95% confidence interval (CI) 1.09-1.80]. Risk did not vary by race/ethnicity. Compared with non bleeders, PTB risk was higher for bleeding with red color (OR(adjusted) = 1.92, 95% CI, 1.32-2.82), for heavy episodes (OR(adjusted) = 2.40, 95% CI 1.18-4.88) and long duration (OR(adjusted) = 1.67, 95% CI 1.17-2.38). CONCLUSIONS: Bleeding associated with PTB was not confounded by common risk factors for bleeding or PTB. PTB risk was greatest for women with heavy bleeding episodes with long duration and red color and would suggest that combining women with different bleeding characteristics may affect the accuracy of risk assessment. These data suggest a candidate etiologic pathway for PTB and warrant further investigation of the biologic mechanisms. PMID- 22052385 TI - Surrogate in vitro fertilization outcome in typical and atypical forms of Mayer Rokitansky-Kuster-Hauser syndrome. AB - BACKGROUND: The genital malformations in Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) are frequently accompanied by associated malformations whose forms were recently classified as typical (isolated uterovaginal aplasia/hypoplasia) and atypical (the addition of malformations in the ovary or renal system). The aim of this study was to compare the surrogate IVF performance of women with typical and atypical forms including their chances of achieving pregnancy. METHODS: The follow-up data on a total of 102 cycles of surrogate IVF in 27 MRKH patients treated in our department between 2000 and 2010 were analysed. Twenty patients with the typical form who underwent 72 IVF cycles were compared with seven patients with the atypical form who underwent 30 IVF cycles. The various examined parameters of these intended mothers were age, hormonal profile during controlled ovarian hyperstimulation and laboratory outcome. RESULTS: The mean number of gonadotrophin ampoules needed for stimulation and treatment duration was significantly higher in the atypical form (3600 +/- 1297IU for 13 +/- 2.3 days versus 2975 +/- 967 IU for 11.6 +/- 1.6 days, P<= 0.01). Serum estradiol and progesterone levels measured on the hCG administration day were similar. A significantly higher mean number of follicles 12.6 +/- 6 versus 8.9 +/- 5.4, P<= 0.03, metaphase II (MII) oocytes 8.7 +/- 5.1 versus 6.7 +/- 4.8, P<= 0.05, fertilizations 6 +/- 3.6 versus 4.4 +/- 3.3, P<= 0.03 and cleaving embryos 5.7 +/ 3.8 versus 4.1 +/- 3.3, P<= 0.01 were available in patients with the typical form compared with those with the atypical form, respectively. There was no significant difference in fertilization rate, cleavage rate or the mean number of transferred embryos. Embryo quality of the transferred ones and pregnancy rate per cycle were also similar between the two groups. CONCLUSIONS: Women with the typical form of MRKH needed fewer gonadotrophins and for a shorter duration for ovarian hyperstimulation. The mean number of follicles, oocytes, MII oocytes, fertilizations and cleaving embryos was higher among women with the typical form. Pregnancy rates were similar since the available number and quality of transferred embryos to the surrogate mother were not affected. PMID- 22052386 TI - Variation in stability of housekeeping genes in endometrium of healthy and polycystic ovarian syndrome women. AB - BACKGROUND: The use of housekeeping genes (HKG) as internal controls for real time qPCR studies of gene expression is based on the assumption of their inherent stability. However, it is unclear whether this stability is maintained in disease states. In order to test this, the present study investigated the expression of specific HKG in the endometrium of healthy and polycystic ovarian syndrome (PCOS) women. METHODS: Endometrial tissue samples were taken from women with PCOS (n= 9) and controls (n= 10). The stability of nine candidate reference genes in the endometrial tissues were evaluated; four encode mitochondrial proteins [ATP5B, succinate dehydrogenase complex subunit A (SDHA), cytochrome c-1, glyceraldehyde 3-phosphatedehydrogenase], two encode ribosomal protein genes (18s ribosomal RNA, ribosomal protein L13A), one for cell structure (SDHA), one for cell signalling (beta actin, ACTB) and one involved in DNA repair (topoisomerase I, TOP1). The expression stability of these HKGs was calculated using geNORM qbasePLUS software, with stability defined by M-values, where higher M-value indicating less stability. In addition, changes in their cycle threshold values were analysed to determine direction of change between groups, and a Mann-Whitney U test was used to determine statistical differences in expression. RESULTS: The most stable HKGs observed across both PCOS endometrium were found to be YWHAZ, CYC1 and ACTB. Further TOP1 demonstrated higher gene expression in the endometrium from PCOS women compared with those from healthy women. CONCLUSIONS: Of the nine HKGs examined, only YWHAZ, CYC1 and ACTB were stable in both control and PCOS endometrium: these should therefore be used as internal controls for quantitative reverse transcription-polymerase chain reaction analysis. Published discrepancies between endometrial gene expression studies may therefore be due in part to in the inappropriate HKG selection, and future gene expression studies should be based on HKG of known stability in both the disease and healthy states to avoid erroneous interpretation of results. PMID- 22052387 TI - Lipopolysaccharide induces cytokine production and decreases extravillous trophoblast invasion through a mitogen-activated protein kinase-mediated pathway: possible mechanisms of first trimester placental dysfunction. AB - BACKGROUND: Defects in extravillous trophoblast (EVT) function could contribute to placental dysfunction resulting in adverse obstetrical outcomes. Adverse obstetrical outcomes have been highly correlated with intrauterine infection; however, the mechanisms linking infection to placental dysfunction remain unclear. We investigated the effects of inflammation on EVT cytokine production and invasion early in pregnancy and determined the cell signaling pathways mediating this response. METHODS AND RESULTS: In our model of inflammation, EVT cells, isolated following first trimester pregnancy terminations (n= 6) were stimulated with lipopolysaccharide (LPS). LPS induced a dose-dependent increase in interleukin (IL)-8 and IL-6 protein production (P < 0.01) and decreased EVT invasion (P = 0.01) versus control. The LPS-mediated changes in cytokine production (P < 0.001) and invasion (P < 0.001) were reversed by dexamethasone (DEX). Exposure to LPS resulted in an increase in mitogen-activated protein kinase (MAPK) signaling pathway phosphorylation, including p44/42 MAPK (P < 0.01), p38 MAPK (P < 0.05), MAPK extracellular signal-regulated kinase 1/2 (MEK1/2) (P< 0.01) and stress-activated protein kinase/c-Jun N-terminal kinase (JNK; P < 0.001), which was reversed by DEX (P < 0.05) for all MAPKs except p38. MAPK-specific inhibitors to MEK1/2 (U0126), p38 MAPK (SB 202190) and JNK (SP 600125) significantly reversed the LPS-mediated increase in IL-6 (P < 0.001) and IL-8 (P < 0.001) production. While U0126 reversed the LPS-induced decrease in EVT invasion (P < 0.001), SB 202190 (P < 0.001) and SP 600125 (P< 0.001) decreased EVT invasion, further indicating that MEK1/2 phosphorylation may be inflammation dependent while p38 MAPK and JNK phosphorylation occurs independently of an inflammatory stimulus. CONCLUSIONS: LPS increased IL-8 and IL-6 and decreased EVT invasion through activation of MAPK signaling. MEK1/2 activation may contribute to placental dysfunction, in the setting of inflammation-associated adverse obstetrical outcomes. PMID- 22052388 TI - Continuous butanol production with reduced byproducts formation from glycerol by a hyper producing mutant of Clostridium pasteurianum. AB - Butanol, a four-carbon primary alcohol (C(4)H(10)O), is an important industrial chemical and has a good potential to be used as a superior biofuel. Bio-based production of butanol from renewable feedstock is a promising and sustainable alternative to substitute petroleum-based fuels. Here, we report the development of a process for butanol production from glycerol, which is abundantly available as a byproduct of biodiesel production. First, a hyper butanol producing strain of Clostridium pasteurianum was isolated by chemical mutagenesis. The best mutant strain, C. pasteurianum MBEL_GLY2, was able to produce 10.8 g l(-1) butanol from 80 g l(-1) glycerol as compared to 7.6 g l(-1) butanol produced by the parent strain. Next, the process parameters were optimized to maximize butanol production from glycerol. Under the optimized batch condition, the butanol concentration, yield, and productivity of 17.8 g l(-1), 0.30 g g(-1), and 0.43 g l(-1) h(-1) could be achieved. Finally, continuous fermentation of C. pasteurianum MBEL_GLY2 with cell recycling was carried out using glycerol as a major carbon source at several different dilution rates. The continuous fermentation was run for 710 h without strain degeneration. The acetone-butanol ethanol productivity and the butanol productivity of 8.3 and 7.8 g l(-1) h(-1), respectively, could be achieved at the dilution rate of 0.9 h(-1). This study reports continuous production of butanol with reduced byproducts formation from glycerol using C. pasteurianum, and thus could help design a bioprocess for the improved production of butanol. PMID- 22052389 TI - Suitability of different beta-galactosidases as reporter enzymes in Bacillus subtilis. AB - The suitability of three beta-galactosidases as reporter enzymes for promoter expression analyses was investigated in Bacillus subtilis with respect to various temperature conditions during cultivation and assay procedures. Starting from the hypothesis that proteins derived from diverse habitats have different advantages as reporters at different growth temperatures, the beta-galactosidases from the thermophilic organism Bacillus stearothermophilus, from the mesophilic bacterium Escherichia coli and from the psychrophilic organism Pseudoalteromonas haloplanktis TAE79 were analysed under control of the constitutive B. subtilis lepA promoter. Subsequent expression of the beta-galactosidase genes and determination of specific activities was performed at different cultivation and assay temperatures using B. subtilis as host. Surprisingly, the obtained results demonstrated that the highest activities over a broad cultivation temperature range were obtained using the beta-galactosidase from the mesophilic bacterium E. coli whereas the enzymes from the thermophilic and psychrophilic bacteria revealed a more restricted usability in terms of cultivation temperature. PMID- 22052390 TI - Efficient use of shrimp waste: present and future trends. AB - The production of shrimp waste from shrimp processing industries has undergone a dramatic increase in recent years. Continued production of this biomaterial without corresponding development of utilizing technology has resulted in waste collection, disposal, and pollution problems. Currently used chemical process releases toxic chemicals such as HCl, acetic acid, and NaOH into aquatic ecosystem as byproducts which will spoil the aquatic flora and fauna. Environmental protection regulations have become stricter. Now, there is a need to treat and utilize the waste in most efficient manner. The shrimp waste contains several bioactive compounds such as chitin, pigments, amino acids, and fatty acids. These bioactive compounds have a wide range of applications including medical, therapies, cosmetics, paper, pulp and textile industries, biotechnology, and food applications. This current review article present the utilization of shrimp waste as well as an alternative technology to replace hazardous chemical method that address the future trends in total utilization of shrimp waste for recovery of bioactive compounds. PMID- 22052391 TI - The involvement of NK cell activation following intranasal administration of CpG DNA lipoplex in the prevention of pulmonary metastasis and peritoneal dissemination in mice. AB - Synthetic oligodeoxynucleotides containing CpG motifs (CpG DNA) can activate immunocompetent cells, which may possess antitumor activity. Previously, we found that when the cationic liposomes complexes formed with CpG DNA (CpG DNA lipoplex) were administered intranasally, they could prevent pulmonary metastasis in mice. However, the mechanisms underlying this process are unknown. In the present study, we show that natural killer (NK) cells play an important role in preventing pulmonary metastasis and peritoneal dissemination in a mouse model of metastatic disease. Further, in vitro, the NK cells obtained from mice treated with CpG DNA lipoplex showed higher cytotoxicity compared with untreated mice and in vivo, depletion of NK cells (achieved through injection of rabbit anti-asialo GM1 serum), abolished the inhibitory effect of CpG DNA lipoplex on pulmonary metastasis and peritoneal dissemination. In contrast, macrophage elimination did not disrupt the effects of the CpG DNA lipoplex. These results suggest that intranasal administration of CpG DNA lipoplex could prevent pulmonary metastasis and peritoneal dissemination by activating NK cells. PMID- 22052393 TI - [Severity scores for predicting clinically relevant outcomes for immunocompetent adult patients hospitalized with community-acquired pneumococcal pneumonia]. AB - Streptococcus pneumoniae is the main cause of community-acquired pneumonia (CAP) in adults. OBJECTIVES: To compare accuracy and discriminatory power of three validated rules for predicting clinically relevant adverse outcomes in patients hospitalized with community-acquired pneumococcal pneumonia. MEASUREMENTS: We prospectively compared the pneumonia severity index (PSI), British Thoracic Society score (CURB-65) and severe CAP score (SCAP) in a cohort of 151 consecutive immunocompetent adult patients hospitalized with pneumococcal pneumonia. Major adverse outcomes were admission to ICU, need for mechanical ventilation, in-hospital complications and 30-day mortality. Mean hospital length of stay (LOS) was also evaluated. The predictive indexes were compared based on sensitivity, specificity, and area under the curve of the receiver operating characteristic. RESULTS: The mean age of 151 immunocompetent adult patients hospitalized with pneumococcal pneumonia was 64 years (range, 16 to 92); 58% were male, 75% had comorbidities, 26% were admitted to the intensive care unit and 9% needed mechanical ventilation. The rate of all adverse outcomes and hospital LOS increased directly with increasing PSI, CURB-65 and SCAP scores. The three severity scores allowed us to predict the risk of in-hospital complications and 30-day mortality. The PSI score was more sensitive and the SCAP was more specific to predict in-hospital complications and the risk of death. However, the SCAP was more sensitive and specific in predicting the use of mechanical ventilation. CONCLUSION: The severity scores validated in the literature allow us to predict the risk of complications and death in adult patients hospitalized with pneumococcal pneumonia. Nevertheless, the clinical indexes differ in their sensitivity, specificity and discriminatory power to predict different adverse events. PMID- 22052392 TI - Hepatic arterial infusion of bevacizumab in combination with oxaliplatin reduces tumor growth in a rat model of colorectal liver metastases. AB - Unresectable colorectal liver metastases are commonly treated with systemic chemotherapy (SCT). Clinical studies on the effect of additional systemic application of bevacizumab (BE), a monoclonal antibody directed against vascular endothelial growth factor, to SCT showed a slight increase of patient survival. Herein, we studied in a rat model of colorectal liver metastasis whether a locoregional application of oxaliplatin (OX) and BE via hepatic arterial infusion (HAI) is more effective to inhibit metastatic growth compared to systemic drug application. Ten days after implantation of CC531 colorectal cancer cells into the left liver lobe of WAG/Rij rats, animals underwent either HAI or systemic intravenous application of BE (5 mg/kg body weight), OX (85 mg/m(2) body surface) or a combination of both. Sham-treated animals received saline and served as controls. Tumor volume was measured at days 10 and 13 using three dimensional ultrasound. At day 13 tumor tissue was analyzed histologically and immunohistochemically. Systemic application of OX, BE or their combination did not affect tumor volume when compared to controls. In contrast, HAI of BE and particularly the combination of BE and OX significantly reduced tumor volume. In the tumor tissue this was associated with a decrease of vascularization and cell proliferation as well as an increase of cell apoptosis, as indicated by a decreased number of PECAM-1- and PCNA-positive cells and an increased number of cleaved caspase-3-positive cells. Locoregional administration of BE, particularly in combination with OX, enhances the inhibitory effect on hepatic metastatic growth compared to systemic application of the drugs. PMID- 22052394 TI - [Laboratory diagnosis of Treponema pallidum infection in patients with early syphilis and neurosyphilis through a PCR-based test]. AB - Syphilis is a sexually transmitted disease caused by Treponema pallidum. The diagnosis is based mainly in clinical presentation and non-specific assays. PCR based diagnosis has been suggested as an attractive alternative method. The aim of this study was the validation of a PCR-based test for the diagnosis of early syphilis (ES) and neurosyphilis (NS). Clinical samples of mucocutaneous lesions and cerebrospinal fluid (CSF) specimens from patients previously diagnosed for ES and NS respectively using an enlarged gold standard, were tested by PCR. The reaction was done using primers targeting the tpN47 gene. Twenty out of 21 mucocutaneous samples from patients diagnosed with ES were positive by PCR, with a clinical sensitivity of 95%. Four out of 8 CSF samples from patients previously diagnosed with NS were positive by PCR, with a clinical sensitivity of 50%. The clinical specificity for both ES and NS was 100%. The PCR sensitivity and specificity for mucocutaneous samples allowed us to implement this assay in our laboratory for routine diagnosis. Although the sensitivity of the PCR in CSF was low, it may be useful to support clinical diagnosis. PMID- 22052395 TI - [Update. Consensus on ventilator associated pneumonia. Second Part: Prophylaxis]. AB - Ventilator associated pneumonia is a life threatening disease, in spite of advances in its treatment, consequently the development of prevention strategies is a key factor in improving the morbidity and mortality in intensive care units (ICU). The new developments in this field in the last years led to the need to update the recommendations done in 2001. Then, a new search and analysis of scientific literature was performed. The obtained data support different strategies highlighting: semi-recumbent position at 45 degrees of patients; incorporation of routinely oral hygiene procedures with chlorhexidine; preference of orotracheal intubation; performing subglotic aspiration; use of standard hand hygiene techniques; not routine change of ventilator circuits; and defining bundles to organize the work at ICU. Some strategies were recommended for being of similar efficacy to others but cost-effective as: use of heat and moisture humidificators; and changing humidificators every 5 to 7 days. The use of open or closed endotracheal suctioning system does not affect the incidence of pneumonia. Some recommendations were not incorporated because of lack of evidence supporting effectiveness, controversial data or doubtful application to our country as selective digestive decontamination. PMID- 22052397 TI - [Streptococcus agalactiae increase in resistance to erythromycin and clindamycin in vaginal-anal colonization in third quarter of pregnancy in one decade of universal screening]. AB - INTRODUCTION: Streptococcus agalactiae (GBS) is the main causative agent of early perinatal sepsis. The acquisition of prevention policies has led to frequent use of intrapartum antibiotics. Surveillance of antimicrobial resistance is indispensable for defining drugs of choice and alternatives for such prophylaxis. OBJECTIVES: To determine the evolution of antimicrobial resistance of GBS from maternal colonization to drugs used in the prevention of neonatal sepsis, between 2002 and 2008. METHODS: We studied 100 GBS positive vaginal and anal samples from pregnant women. Disc diffussion susceptibility method was performed for penicillin, ampicillin, cefazolin, erythromycin and clindamycin according to the Clinical and Laboratory Standards Institute (CLSI). RESULTS: We analyzed the susceptibility of 99 strains. Seventeen were resistant to erythromycin (17.1%) and 13 were resistant to clindamycin (13.1%). Thirteen of the 17 strains resistant to erythromycin had the MLS phenotype (resistance to erythromycin and clindamycin) and 4 had the M phenotype (resistance to erythromycin only). Within the MLS phenotype, resistance was constitutive in 9 strains, and induced in 4 strains (positive D test). Compared with 2002 there was a significant increase in resistance to clindamycin (from 3.27% to 13.1% p < 0.002) and erythromycin (1.09% to 17% p < 0.001). 100% GSB remained sensitive to penicillin and ampicillin. CONCLUSIONS: GBS remains highly susceptible to drugs of choice for prevention of perinatal sepsis. There is a significant increase in antimicrobial resistance to clindamycin and erythromycin. Therefore, it is necessary to request susceptibility testing in GBS from third trimester of pregnancy screening in patients allergic to penicillin. PMID- 22052398 TI - [Epidemiologic description of a post-pandemic outbreak of influenza A H1N1 2009 in an isolated community of the region of Aysen, Chilean patagonia]. AB - On August 10th 2010 the World Health Organization (WHO)announced the end of the influenza A H1N1 2009 pandemic. On August 13th, three cases of influenza A H1N1 2009 from the local school were confirmed at the Hospital de Chile Chico. An epidemiological investigation was conducted in conjunction with the regional health authority (SEREMI), in order to monitor the outbreak and establish appropriate control strategies. During the study period (august 7 to 21), 304 cases of influenza-like-illness (ILI) were reported, with an incidence of 6171 cases per 100.000 in epidemiological week no 33. Most of the affected people were 19 years old or younger (68% of cases). Hospitalized patients (n: 7) had a favorable outcome, without severe symptoms or need for transfer to an intensive care unit. A female patient with a congenital heart defect who had not been vaccinated was the only fatal case. The outstanding features of this post pandemic outbreak were its intensity and the demonstration of the importance of control measures to prevent further spread of influenza A H1N1 2009 infections, in the community setting. PMID- 22052399 TI - [Etiology of pneumonia in chilean HIV-infected adult patients]. AB - OBJECTIVES: To establish the etiology of pneumonia and to compare the yield of diagnostic techniques for diagnosis of Pneumocystis jiroveci and Mycobacterium tuberculosis infections in HIV-1-infected patients. PATIENTS AND METHODS: Subjects underwent sputum induction and bronchoalveolar lavage (BAL). Gram, Ziehl Neelsen, silver stain (SS) and immunofluorescense staining (IF) for P. jiroveci, fluorescent stain for mycobacteria, PCR for P. jiroveci and M. tuberculosis, aerobic, fungal and mycobacterial cultures, respiratory viruses and CMV cultures were performed on the sputum and BAL. IgM for Mycoplasma pneumoniae and Chlamydophyla pneumoniae, and Legionella pneumophila urinary antigen were also obtained. RESULTS: Sixty patients were included. An etiologic diagnosis was made in 97%. Pneumocystis jiroveci was the most frequent etiology (58%) followed by Streptococcus pneumoniae (12%), and Mycobacterium avium complex (12%). Mycobacterium tuberculosis was found in 5%. CONCLUSIONS: The comparison of diagnostic methods for P. jiroveci showed a higher sensitivity of IF and SS in BAL than in sputum, however PCR was equally sensitive in both samples. With this approach a precise etiologic diagnosis was reached in the great majority of patients. The most common etiology was P. jiroveci. IF in BAL remains the gold standard for diagnosis of P. jiroveci pneumonia. PMID- 22052400 TI - [Evaluation of quantitative cultures of endotracheal aspirates for pediatric ventilator-associated pneumonia diagnosis: analytic, prospective study]. AB - INTRODUCTION: Ventilator-associated pneumonia (VAP) is dificult to diagnose because of the absence of a gold standard. AIM: To evaluate the use of quantitative cultures of endotracheal aspirates for diagnosis of pediatric VAP and to obtain acceptable sensitivity and specificity cutoff points. PATIENTS AND METHODS: Prospective, analytic study which included patients under 15 years, who were connected to mechanical ventilation at Hospital Luis Calvo Mackenna's intensive care units. They were classified as cases or controls according to NNIS criteria. RESULTS: During a period of 21 months we recruited a total of 43 patients with a mean age of 16 months. We obtained endotracheal aspirated samples to perform quantitative cultures. Most frequently isolated pathogens were Staphylococcus aureus (34.5%) and non-fermentative Gram-negative bacilli (24.1%). We obtained a sensitivity of 88%, specificity of 70%, PPV of 82%, and NPV of 79% for samples greater than 10(6) CFU. CONCLUSIONS: Quantitative culture of endotracheal aspirates is a reliable method for diagnosing pediatric VAP when the value is greater than 10 CFU. PMID- 22052401 TI - [Actinomyces urogenitalis]. PMID- 22052402 TI - [Importance of images and etiological diagnosis in the immunocompromised patient with central nervous system envolvement. Part II]. AB - We present the case of a 12-year-old boy with acute lymphocytic leukemia who developed pneumonia and multiple brain infarcts compatible with acute necrotic encephalitis. The infectious disease screening tests revealed influenza A H1N1 virus, Staphylococcus aureus in broncho alveolar lavage, E. coli and galactomannan antigen in blood. CNS influenza associated complications are reviewed. This case highlights the importance of magnetic resonance imaging as a diagnostic tool in the assessment of immunocompromised patients with CNS compromise and the value of brain biopsy in the final identification of an infectious disease etiology. PMID- 22052403 TI - [Cervical mass caused by Salmonella Typhimurium as a clinical presentation of AIDS in a HIV-positive patient]. AB - Infections due to non-typhi salmonellae (NTS) generally cause a mild and self limited gastrointestinal disease. However, there have been reports of atypical and severe presentations in immunocompromised patients. We report the case of a male patient who consulted with a cervical mass. He was found to be HIV-positive and Salmonella Typhimurium was isolated in one blood culture and cervical mass tissue culture. We discuss the relevance of infections by NTS in immunodeficient patients because they present with more severe illness than normal population. We emphasize the importance of NTS bacteremia as a marker of underlying immunodeficiency. We present some localized infection sites reported in the literature and their relation with particular diseases. We discuss the future relevance that an early start of antiretroviral therapy (ART) may have in HIV patients with NTS acute bacteremia or focal infections. Because infections by NTS can be severe and highly lethal they must be considered in the differential diagnosis of causative organisms of localized infections and bacteremia in HIV patients. PMID- 22052404 TI - [Espondilodiskitis caused by Kingella kingae in children: a case report]. AB - During the last years, spondilodiskitis due to Kingella kingae has been a new target of interest, since it is the second agent that causes non tuberculous espondilodiskitis in children, after Staphylococcus aureus. Its clinical presentation is very inespecific, sometimes with fever, abdominal or lumbar disconfort, nocturnal pain, altered walking and sedestation. Images, culture methods and PCR (polymerase chain reaction) can be helpful for diagnosis, although in an important percent of the cases, etiology cannot be determined. Although there are no established guidelines for treatment, before the suspicion, empiric antibiotic treatment should be started for good prognosis. We describe a case of a 3 year old boy, who had this disease and then a review about spondilodiskitis in childhood and microbiological aspects of Kingella kingae. PMID- 22052405 TI - [What was the plague of Athens?]. AB - In the year 430 B.C., at the beginning of the second year of the Peloponessian War, a terrible epidemic fell upon Athens and the most populous cities in Attica. It would last for just over four years and it would kill 100.000 people, a quarter to a third of the population. We know about it through the masterly description made by Thucydides in his History of the Peloponnesian War. His narrative has withstood twentyfive centuries due to its medical interest and, above all, its great dramatic force. The description of symptoms and signs, their evolution, and the consequences upon persons and moral and social order has captivated physicians, philologists and classical historians ever since. It has inspired literary works and hundreds of medical articles, with no agreement having been reached upon its cause or consequences, or if it is history or tragedy, or even if there is a single answer to these alternatives. PMID- 22052406 TI - [Hepatic abscess as first manifestation of pneumococcal invasive disease]. AB - Pneumococcal invasive disease is an important cause of morbidity and mortality in different population groups. Most cases originate from an airway infection. We describe a patient with diabetes mellitus who presented a liver abscess as first manifestation of pneumococcal invasive disease, without respiratory symptoms. The patient was treated with percutaneous drainage and systemic antibiotics with good results. Streptococcus pneumoniae should be considered among the possible etiologies of hepatic abscess, even in absence of respiratory symptoms. PMID- 22052407 TI - Optimal sample sizes for phase II clinical trials and pilot studies. AB - Methodology for sample size calculation for phase III clinical trials is well established and widely used. In contrast, for earlier phase clinical trials or pilot studies, although there is an acceptance that the methods used for phase III trials are not appropriate, there is little consensus over methods that should be used. This paper explores this problem from a Bayesian decision theoretic perspective. The aim is to obtain sample sizes that would be appropriate for studies funded by a large funder such as a public sector body or major pharmaceutical company. The sample sizes obtained are optimal in that they minimise the average number of patients required per successfully identified effective therapy or equivalently maximise the number of effective therapies successfully identified over a long period. It is indicated that the number of patients included in a phase II clinical trial should be approximately 0.03 times that planned to be included in the phase III study. This is similar to that proposed by other researchers in this area, though rather smaller than actually used for many phase II trials. PMID- 22052408 TI - Dynamic properties of photosystem II membranes at physiological temperatures characterized by elastic incoherent neutron scattering. Increased flexibility associated with the inactivation of the oxygen evolving complex. AB - Elastic incoherent neutron scattering (EINS), a non-invasive technique which is capable of measuring the mean square displacement of atoms in the sample, has been widely used in biology for exploring the dynamics of proteins and lipid membranes but studies on photosynthetic systems are scarce. In this study we investigated the dynamic characteristics of Photosystem II (PSII) membrane fragments between 280 and 340 K, i.e., in the physiological temperature range and in the range of thermal denaturation of some of the protein complexes. The mean square displacement values revealed the presence of a hydration-sensitive transition in the sample between 310 and 320 K, suggesting that the oxygen evolving complex (OEC) plays an important role in the transition. Indeed, in samples in which the OEC had been removed by TRIS- or heat-treatments (323 and 333 K) no such transition was found. Further support on the main role of OEC in these reorganizations is provided by data obtained from differential scanning calorimetry experiments, showing marked differences between the untreated and TRIS-treated samples. In contrast, circular dichroism spectra exhibited only minor changes in the excitonic interactions below 323 K, showing that the molecular organization of the pigment-protein complexes remains essentially unaffected. Our data, along with earlier incoherent neutron scattering data on PSII membranes at cryogenic temperatures (Pieper et al., Biochemistry 46:11398 11409, 2007), demonstrate that this technique can be applied to characterize the dynamic features of PSII membranes, and can be used to investigate photosynthetic membranes under physiologically relevant experimental conditions. PMID- 22052409 TI - BapC autotransporter protein of Bordetella pertussis is an adhesion factor. AB - Bordetella pertussis, the causative agent of whooping cough, attaches to mucosal surfaces in upper respiratory tract, where it produces, a variety of surface associated and secreted molecules. Among various secreted products, some of the proteins belonging to autotransporter family; pertactin (Prn), bordetella resistance to killing (BrkA) and a newly identified member, bordetella autotransporter protein-C (BapC), are investigated in this study for their adherence potential to various respiratory and non-respiratory tract specific cell lines. Our results reveal that BapC and Prn mutants adhere significantly less (p < 0.0001 and p < 0.05) respectively to human non-respiratory (HeLa-229) and murine macrophages (P-388 D-1) cells compared to their wild-type strains. Prn, BrkA and BapC share no homology in their passenger domains except existence of common motifs arginine-glycine-asparctic (RGD) and glycosaminoglycan binding site (SGXG). We have shown that RGD and SGXG motifs are present in the coiled region in Prn and BrkA proteins with the exception in BapC where R (463) of RGD and S (597) of SGXG motif were observed in beta sheet of the modeled protein structures. Therefore, there is possibility that such arrangement of motifs can confer greater probability of BapC in better selective adherence to binding sites on the HeLa-229 and P-388 D-1 cell lines. PMID- 22052411 TI - Rosiglitazone reverses mitomycin C resistance in human gastric cancer cells. AB - INTRODUCTION: To explore the mechanisms of rosiglitazone (ROS), a selective peroxisome proliferator-activated receptor gamma ligand, in reversing mitomycin C (MMC) resistance in a human drug-resistant gastric cancer cell line. METHODS: The vincristine-resistant human gastric cancer cell line SGC7901/VCR and its parental cell line SGC7901 were treated with ROS, MMC (negative control), cyclosporine A+MMC (positive control) or ROS+MMC. A tetrazolium blue (methyl thiazolyl tetrazolium) assay was used to evaluate the sensitivity to these treatments. Flow cytometry analysis and acridine orange-ethidium bromide (AO-EB) fluorescent staining were used to determine the effects of ROS on MMC-induced apoptosis. Reverse transcription polymerase chain reaction and western blotting were used to measure the expression of multidrug resistant 1 (MDR1), Livin and P-glycoprotein (P-gp). RESULTS: ROS administration dose dependently increased the reversal index in MMC-treated SCG7901/VCR cells. ROS increased apoptosis in SGC7901/VCR cells compared with the blank group and MMC group. ROS+MMC also increased apoptosis in SGC7901/VCR cells compared with other groups (P < 0.05 or P < 0.01). The mRNA expression of MDR1 and Livin and the protein expression of P-gp in SGC7901/VCR cells were significantly higher than those in SGC7901 cells (P < 0.01). However, ROS or ROS+MMC treatment markedly upregulated the mRNA expression of MDR1 and Livin and the protein expression of P-gp in SGC7901/VCR cells (P < 0.01). CONCLUSIONS: ROS reverses MMC resistance in human gastric cancer SGC7901/VCR cells by reducing expression of MDR1, Livin and P-gp and increasing apoptosis. PMID- 22052412 TI - Failure of echinocandin therapy in the treatment of Candida glabrata chorioretinitis. AB - Echinocandins are commonly used as initial empiric therapy in cases of moderate to severe invasive candidiasis. The authors demonstrate that caution should be exercised in applying this approach in certain clinical situations. A case of Candida glabrata fungemia and associated chorioretinitis that was clinically resistant to therapy with micafungin but appeared to resolve with amphotericin B is presented. The authors then briefly review current issues regarding the diagnosis and treatment of C glabrata chorioretinitis. PMID- 22052413 TI - Percutaneous transluminal angioplasty for radial-cephalic fistulae with stenosis at the arteriovenous junction. AB - INTRODUCTION: The aim of this study was to analyze the predictive factors for initial success and long-term patency of percutaneous transluminal angioplasty for radial-cephalic (RC) fistulae with stenosis at the arteriovenous junction (AVJ). Stenosis at the AVJ of RC fistulae involves both the feeding artery and drainage vein and is similar to a bifurcation lesion, which carries a worse outcome. The optimal intervention method for this type of lesion is currently unknown. METHODS: Ninety-one percutaneous transluminal angioplasty procedures for stenosis at the AVJ of RC fistulae were reviewed retrospectively. Parameters including age, sex, location of the RC fistula (right or left arm), approach site (radial artery or cephalic vein) and involvement of proximal radial artery (PRA) dilatation were analyzed for initial procedure success and long-term patency rates. RESULTS: The total initial success rate was 94.5%. The existence of total occlusion was recognized as the only factor significantly associated with a high procedural failure rate (39% versus 0%, P < 0.001). For long-term patency rate, the only significant factor was the involvement of PRA dilatation (P = 0.026 by Cox-Mantel and 0.03 by generalized Wilcoxon methods). The 6-month, 1-year and 18 month patency rates were 64%, 45.3% and 20.9%, respectively, for all procedures, and 70.7% versus 57.8%, 56.1% versus 35.6% and 36.6% versus 6.7% for procedures with and without PRA dilatation, respectively. CONCLUSIONS: In treating stenosis at the AVJ of RC fistulae, while initial procedural failure occurred mainly in occluded lesions, involvement of PRA dilatation was the only significant predictive factor associated with long-term patency. PMID- 22052414 TI - Role of dentifrices with essential oil formulations in periodontal healing. AB - INTRODUCTION: Essential oil (EO)-formulated dentifrices have significant effectiveness in reducing periodontal inflammation. This study aimed to review the role of dentifrices with EO formulations in periodontal healing. METHODS: Databases were explored from 1968 until March 2010. The focused question was what is the impact of dentifrices with EO formulations on periodontal wound healing? Databases were searched using the following terms in various combinations: "essential oil," "periodontal healing," "mouthrinse," "mouth-wash" and "periodontitis." RESULTS: Twenty studies were included. The numbers of participants ranged from 20 to 316 individuals (aged 18-70 years) and were rinsing with the EO-formulated dentifrices at least twice daily for 1 week to 48 weeks. Fourteen clinical studies showed reduced periodontal inflammatory conditions in the test group (individuals using EO dentifrices) compared with the placebo group. Three studies showed a reduction in periodontal pathogens in the test group compared with the placebo group. In 1 study, the microbiological findings remained inconclusive between the 2 groups. CONCLUSION: EO-formulated dentifrices have beneficial effects on the clinical and microbiological parameters of periodontal inflammation. PMID- 22052415 TI - Vomiting-induced gastric emphysema: a rare self-limiting condition. AB - Radiological evidence of presence of air or gas within the stomach wall is termed "gastric pneumatosis" and is considered an ominous sign. However, the etiological associations range from benign self-limiting causes to life-threatening emergencies. The authors report the case of gastric pneumatosis in a 34-year-old man who presented to the emergency department with severe abdominal pain after multiple episodes of vomiting. The authors also review the clinical associations of this uncommon condition and discuss risk stratification and management strategies. PMID- 22052416 TI - Acute dyspnea after colonoscopy. PMID- 22052417 TI - Symptomatic giant left atrium. PMID- 22052418 TI - Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: reduction post-bortezomib monotherapy. AB - Sclerostin is a Wingless and Int-1 inhibitor, which is produced by osteocytes and inhibits osteoblast-driven bone formation. Sclerostin is implicated in the pathogenesis of bone loss in metabolic bone disorders but there is no information for its effect on multiple myeloma (MM)-related osteolytic disease. We evaluated circulating sclerostin in 157 newly diagnosed patients with symptomatic myeloma, in 25 with relapsed myeloma who received bortezomib monotherapy, in 21 patients with monoclonal gammopathy of undetermined significance (MGUS), and in 21 healthy controls. Patients with active myeloma had elevated circulating sclerostin compared to MGUS patients and controls (p < 0.01). MM patients who presented with fractures at diagnosis (n = 34) had very high levels of circulating sclerostin compared with all others (p < 0.01), whereas sclerostin correlated negatively with bone specific alkaline phosphatase (a bone formation marker; r = -0.541, p < 0.0001) and positively with C-telopeptide of collagen type-1 (a bone resorption marker; r = 0.524, p < 0.0001). Patients with International Staging System (ISS) 3 disease had higher circulating sclerostin compared to ISS-1 and ISS-2 MM (p = 0.001). Furthermore, patients with high sclerostin (upper quartile, n = 40) had a median survival of 27 months versus 98 months of all others (p = 0.031). Relapsed MM patients had higher levels of circulating sclerostin even compared to newly diagnosed patients (p < 0.01). Bortezomib monotherapy resulted in a reduction of sclerostin by almost 50% in both responders and non-responders. These results suggest that patients with active myeloma have elevated circulating sclerostin, which correlated with advanced disease features including severe bone disease. Our study indicates sclerostin as a possible target for the development of novel therapies to enhance osteoblast function in myeloma. PMID- 22052419 TI - National trends in laryngeal cancer surgery and the effect of surgeon and hospital volume on short-term outcomes and cost of care. AB - OBJECTIVES/HYPOTHESIS: The past 2 decades have witnessed an increase in the use of chemoradiation in the treatment of laryngeal cancer. We sought to characterize contemporary patterns of laryngeal cancer surgical care and the effect of volume status on surgical care and short-term outcomes. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Using the Nationwide Inpatient Sample database, temporal trends in laryngeal cancer surgical care were evaluated in 78,478 cases performed in 1993 to 2008. Relationships between volume and mortality, complications, length of stay, and costs were evaluated in 24,856 cases performed in 2003 to 2008 using regression analysis, with adjustment for patient and provider characteristics. RESULTS: Laryngeal cancer surgery in 2001 to 2008 was associated with increased utilization of high-volume hospitals (odds ratio [OR]=2.0, P=.039), a decrease in partial and total laryngectomy procedures (OR=0.7, P<.001), an increase in flap reconstruction (OR=1.6, P<.001), prior radiation (OR=2.2, P<.001), comorbidity (OR=1.6, P<.001), and wound complications (OR=4.0, P<.001), compared to 1993 to 2000. High-volume hospitals were significantly associated with partial laryngectomy (OR=1.8, P=.026) and flap reconstruction (OR=1.8, P=.027). High-volume surgeons were associated with partial laryngectomy (OR=1.7, P=.048), flap reconstruction (OR=1.6, P=.029), prior radiation (OR=2.2, P=.013), and comorbidity (OR=0.4, P=.008). After controlling for all other variables, a statistically significant negative correlation was observed between surgery at a high-volume hospital and length of hospitalization, and surgery by a high-volume surgeon was associated with even greater reductions in length of hospitalization as well as lower hospital-related costs. CONCLUSIONS: These data reflect changing trends in the primary management of laryngeal cancer, with meaningful differences in the type of surgical care provided by high-volume providers. PMID- 22052420 TI - Maternity waiting homes and institutional birth in Nicaragua: policy options and strategic implications. AB - With the aim of promoting institutional births and reducing the high maternal and child mortality rates in rural and poor zones, the government of Nicaragua is supporting the creation of maternity waiting homes. This study analyzes that strategy and examines the factors associated with the use of maternity waiting homes and institutional birth. To that end, we apply a quantitative approach, by means of an econometric analysis of the data extracted from surveys conducted in 2006 on a sample of women and parteras or traditional birth attendants, as well as a qualitative approach based on interviews with key informants. Results indicate that although the operation of the maternity waiting homes is usually satisfactory, there is still room for improvement along the following lines: (i) disseminating information about the homes to both women and men, as the latter frequently decide the course of women's healthcare, and to parteras, who can play an important role in referring women; (ii) strengthening the postpartum care; (iii) ensuring financial sustainability by obtaining regular financial support from the government to complement contributions from the community; and (iv) strengthening the local management and involvement of the regional government. These measures might be useful for health policy makers in Nicaragua and in other developing countries that are considering this strategy. PMID- 22052421 TI - Perioperative outcomes of surgical procedures for symptomatic fundoplication failure: a retrospective case-control study. AB - BACKGROUND: Anatomic failure with recurrent gastroesophageal reflux disease (GERD) or related symptoms following fundoplication is a well-described occurrence. Occasionally, reoperative surgery is required. The morbidity of revisional surgery can be quite high, and the clinical outcomes may not be as good as is observed following primary antireflux operations. METHODS: Data were obtained from a prospectively maintained foregut surgery database and via follow up survey. Patients who underwent surgery for symptomatic failed fundoplication were included. A control group consisting of the same number of patients who underwent a first-time fundoplication for GERD was randomly selected from the same database. Anatomic failure of the original fundoplication was confirmed in all cases with upper endoscopy and an upper-GI series. Perioperative outcomes were compared between study groups. Visick scores were attained via phone follow up along with satisfaction scores related to the outcome. RESULTS: From January 2003 to January 2010, 38 patients underwent revisional operations for failed fundoplication at our institution. The majority of patients (74%) had one previous failed attempt at fundoplication (range = 1-3). The most common mechanism of failure was hiatal hernia with recurrent GERD (79%). Reoperative patients were similar to their controls (age, sex, and body mass index). Reoperative surgery took longer, patients remained in the hospital longer, and these patients experienced more complications. Despite this fact, satisfaction with the outcomes of surgery was high in each group. The majority of patients in each study group reported Visick scores of grade 1 (no symptoms, resolved) or grade 2 (mild occasional symptoms, easily controlled) after surgery. CONCLUSION: Compared to primary antireflux surgery, revisional operations are associated with longer mean operating times, increased length of hospital stay, and increased morbidity. Despite this fact, the majority of patients are satisfied with the outcomes of revisional surgery for failed fundoplication, and symptomatic outcomes are good. PMID- 22052422 TI - Endoscopic thyroidectomy via bilateral axillo-breast approach (BABA): review of 512 cases in a single institute. AB - BACKGROUND: Various techniques for endoscopic thyroidectomy have been introduced in the past decade, and the cosmetic superiority of these techniques has been universally acknowledged. We developed the endoscopic thyroidectomy via bilateral axillo-breast approach (BABA) and have performed more than 500 operations. The aims of this study are to analyze the surgical outcomes and to evaluate the effectiveness and safety of BABA endoscopic thyroidectomy. PATIENTS AND METHODS: Between February 2004 and March 2008, 512 patients with thyroid diseases underwent BABA endoscopic thyroidectomy. The criteria analyzed were clinicopathologic characteristics, types of operation, operation time, tumor-node metastasis (TNM) stage on the basis of the 7th edition of the American Joint Committee on Cancer (AJCC), results after radioactive ablation therapy, and recurrence of disease in these patients. RESULTS: Of 512 patients, 397 had a malignant tumor and 115 had benign thyroid disease. Eight patients were diagnosed with Graves' disease, and nine patients underwent completion thyroidectomy. Three cases were subjected to open thyroidectomy due to uncontrolled bleeding. Mean operation time was 151.2 +/- 38.1 min for total and near-total thyroidectomy, and 141.7 +/- 50.1 min for subtotal thyroidectomy and lobectomy. Regarding postoperative complications, transient hypocalcemia occurred in 31.1% of patients and permanent hypoparathyroidism occurred in 4.2% of patients. Transient hoarseness occurred in 20.3% of patients, and permanent vocal cord palsy occurred in 1.7%. Mean hospital stay after operation was 3.34 +/- 0.8 days (range 3-7 days), and mean follow-up period was 57.1 +/- 17.6 months (range 38.5-71.7 months). There were eight cases of recurrent thyroid carcinoma, and no mortality has occurred up to the present time. CONCLUSIONS: Endoscopic thyroidectomy via bilateral axillo-breast approach is a safe and effective method that gives good surgical completeness, a low rate of postoperative complications and recurrence, and an excellent cosmetic result. Therefore, this method is a good choice for patients with surgical thyroid diseases. PMID- 22052423 TI - James F. Lind Sr. MD, CM, FACS, FRCC: a tribute to a surgical gastroenterologist and educator. AB - BACKGROUND: This manuscript is a tribute to James Forest Lind Sr., who died on October 22, 2010. He was a founding past president of the Society of American Gastrointestinal Surgeons and devoted his life to surgical gastroenterology and academic surgery. METHODS: This manuscript was prepared by reviewing his life with input from family, friends, and colleagues. It represents a compilation of a 50-year career in medicine with enormous contributions to gastrointestinal surgery and education. RESULTS: Jim Lind Sr. was born in Fillmore, Saskatchewan, Canada on November 22, 1925. He spent his formative years in Keewatin, Ontario, Canada. After graduating from high school, he served in the Royal Canadian Air Force and then received his MD degree from Queens University. He went on to surgical internship at Hamilton General Hospital, followed by a surgical residency at Queens University. Following residency, he spent 2 years in England as a senior registrar and then completed a fellowship in gastrointestinal physiology at the Mayo Clinic. Jim Lind took his first academic appointment when he joined the faculty at the University of Manitoba in Winnipeg, Manitoba. During his distinguished career in academic surgery, Jim Lind served as the chairman of surgery at three intuitions: the University of Manitoba, McMaster University, and Eastern Virginia Medical School. CONCLUSIONS: James F. Lind Sr.'s legacy as a human being will be that he always pursued excellence in everything he did. He lived and breathed academic surgery and was passionate about surgical education. He will be missed by family, friends, and colleagues. PMID- 22052424 TI - New methods for innovation: the development of a toolbox for natural orifice translumenal endoscopic surgery (NOTES) procedures. AB - BACKGROUND: Devices used for flexible intralumenal procedures are inadequate when used for intraperitoneal surgical procedures such as cholecystectomy. OBJECTIVE: To assess/address limitations of flexible endoscopic devices in intraperitoneal surgery. DESIGN: To describe processes used to invent new devices to facilitate this new surgical genre. SETTING: Engineering laboratory. PATIENTS: None. INTERVENTIONS AND INVENTIONS: Reviews of the limitations of flexible endoscopic instruments and instrumentation/invention needs for a "NOTES cholecystectomy" were completed. MAIN OUTCOME MEASURES: The appropriateness of existing methods of device innovation was evaluated against an inventory of new technologies necessary to perform NOTES. The deficiencies in traditional innovation methods led to the creation of a novel process for invention of new medical devices: the "Inventorama." METHODS: Cooperation between clinicians and industry to develop device concepts to enable NOTES. RESULTS: The devices included: (1) steerable flex trocar, (2) rotary access needle, (3) bipolar hemostasis forceps, (4) Maryland dissectors, (5) articulating hook knife, (6) rotating hook knife, (7) articulating graspers, (8) scissors, (9) ligating clip applier, and (10) tissue apposition system. Six of these ten were built and tested as initial crude prototypes in the Inventorama process; two underwent major modifications. Three were invented via alternate methods, including by independent clinicians. CONCLUSIONS: A new method for efficient medical device invention and development was created to address key technology needs for NOTES. The result was a "toolbox" of devices designed to address the key surgical activities necessary for advanced intralumenal and translumenal flexible endoscopic procedures. PMID- 22052425 TI - One-trocar-assisted nephrectomy (OTAN): initial experience and codification of a technique. AB - BACKGROUND: Laparoscopic nephrectomy in children has gradually become a reasonable alternative to open nephrectomy and, besides, a retroperitoneal approach seems more logical than transperitoneal approach to perform nephroureterectomy for benign disease, as in open surgery. To further reduce the access-related complications, we propose a retroperitoneal one trocar-assisted nephrectomy (OTAN). We report our experience with minimally invasive OTAN for the treatment of benign renal disease. METHODS: A total of 27 OTANs were performed at our institution between 2003 and 2009. The median patient age was 7.6 (range, 2 32 months). Indications for unilateral nephrectomy were multicystic dysplastic kidney (MCDK) in 23 cases (85.2%), dysplastic kidney in 3 cases (11.1%), and reflux nephropathy in 1 case (3.7%). RESULTS: The median operative time from the initial incision to skin closure was 60 min. Perioperative transfusion was not required in any cases. No major perioperative complications developed. Conversion to open surgery was necessary in four cases (14.8%): in three cases for a small working space arising from a peritoneal perforation, and in one case for a difficult visualization of the parenchyma (renal fusion not detected by preoperative ultrasound evaluation). Most patients were allowed oral intake on postoperative day 1. The median hospital stay was 2 (range, 2-3) days; the cosmetic results were excellent. Convalescence was uneventful in all patients. CONCLUSIONS: Although the indications for a nephrectomy in case of benign disease remain limited, when a little child has small, poorly functioning kidneys that must be removed, a one trocar-assisted approach for nephrectomy is usefully a safe and effective treatment choice. The procedure can be easily performed through a small incision with minimal morbidity, comparable operative time, and excellent cosmesis without excessive postoperative pain issues, allowing early discharge home. PMID- 22052426 TI - Video. Transanal specimen retrieval using the transanal endoscopic microsurgery (TEM) system in minimally invasive colon resection. AB - BACKGROUND: During laparoscopic colectomy, the specimen is retrieved through substantial incisions, which increase postoperative pain, wound infections, and incisional hernias. In the era of natural orifice transluminal endoscopic surgery (NOTES), incisionless transrectal approaches for colon resections have been investigated with promising results [4-6]. Transanal retrieval of the colonic specimen in laparoscopic colectomy has been described but not widely adopted, although it seems to be an appealing step towards NOTES colectomy. We have used the TEM rectoscope (Richard Wolf Medical Instruments Corporation, Vernon Hills, IL, USA) as a retrieval conduit, which facilitates transanal extraction of the specimen, and protects the rectal edge and anal sphincter during laparoscopic left colectomy. TECHNIQUE: After standard laparoscopic dissection and vascular control, the colon is divided distally, whereas the proximal colonic end is ligated to prevent fecal spillage. The TEM rectoscope is advanced through the rectal stump. The proximal colon is grasped and withdrawn through the rectoscope. The colon is stapled off proximally, and the specimen is removed transanally. An anvil is introduced into the pelvis through the rectoscope and inserted in the descending colon through a colotomy, which is subsequently sealed with an endo loop. The rectoscope is withdrawn, and the rectal stump edge is stapled off. A circular stapler is introduced in the rectum, and end-to-end anastomosis is performed. DISCUSSION: The extraction incisions in laparoscopic colectomy increase invasiveness and compromise the "purity" of the laparoscopic approach. Retrieval of the specimen through natural orifices constitutes a stepping stone in the transition to future incisionless NOTES colectomy. These techniques have not been widely adopted because of technical difficulties and concerns regarding trauma. In our experience, transanal retrieval of the colonic specimen is hampered by friction between the specimen and the rectum, which requires countertraction to the edges of the open rectal stump. These manipulations are time consuming and increase the risk of injury, even when retrieval bags are used. The TEM rectoscope allows gentle dilation of the anus, provides stability during extraction, and protects the edges of the rectum, therefore decreasing the risk of rectal or anal canal injuries. It maintains pneumoperitoneum and eases retrieval of the specimen through the large-caliber metal conduit. Alternative options in the form of a rigid conduit would be the use of the transanal endoscopic operation device (Karl Storz, Tuttlingen, Germany), the plastic McCartney tube (Tyco Healthcare, Norwalk, CT, USA) used for transvaginal operations, or an anecdotally reported, "homemade" rectoscope from a customized polyvinyl chloride tube. Potential limitations of this technique include the increased cost of acquiring and using the TEM rectoscope, although this should not be significant if this reusable system is already available for transanal procedures. The 4 cm diameter of the TEM rectoscope can also be a limiting factor in the case of large, bulky, incompressible specimens or large colonic tumors. We have also avoided using this technique in patients with preexisting anal sphincter dysfunction and fecal incontinence, as well as in the presence of severe perianal disease (i.e., fistulae or fissures). Naturally, the open lumen in the peritoneal cavity raises concerns regarding bacterial contamination and potential tumor cell seeding in cases of cancer. Preliminary evidence on these issues comes from TEM and NOTES research without obvious signs of increased risk currently. We do not perform preoperative bowel preparation for our colectomies, but we do perform rectal enema with Betadine solution at the beginning of the procedure. CONCLUSIONS: Use of the TEM system facilitates transanal removal of the specimen and protects the anorectum during laparoscopic colectomy. PMID- 22052427 TI - Quantifying mental workloads of surgeons performing natural orifice transluminal endoscopic surgery (NOTES) procedures. AB - BACKGROUND: During natural orifice transluminal endoscopic surgery (NOTES), surgeons often have difficulties orienting the surgical view and manipulating instruments accurately, which increases their level of mental and physical fatigue. This study quantified mental workload by measuring the spared mental resources of surgeons performing NOTES training tasks. METHODS: Assessment of mental workload was conducted in both a benchtop and a hybrid animal model. Using the benchtop model, surgeons were required to pass a ring as many times as possible in 6 min. Using the hybrid model, surgeons were required to dissect the gallbladder. While performing those primary tasks, the surgeon was required to identify true visual signals among many false signals displayed on an adjacent monitor. They were asked to repeat the trials using laparoscopy. The surgeons' performance on the primary and secondary tasks using the NOTES and laparoscopic approaches were recorded and compared. RESULTS: The nine surgeons who completed the trials in the benchtop model successfully transferred 13 +/- 4 rings between targets using laparoscopy compared with a mean of 1.2 +/- 1.0 rings transferred using NOTES (P < 0.001). The surgeons detected visual signals at a 74% rate using laparoscopy, which was significantly higher than the 54% detection rate with the NOTES procedure (P = 0.005). Using the hybrid model, 10 surgeons achieved a 55% accuracy rate performing the laparoscopic task. This was found to be significantly higher (P = 0.006) than when the task was performed using the NOTES platform (39%). CONCLUSION: The results showed that performance of a task using the NOTES platform increases surgeons' mental workload. Because difficulty performing NOTES is associated with flexible endoscopy, the authors expect that new operating systems providing stable platforms will help to decrease the mental workload of surgeons and enhance eye-hand coordination in performing NOTES. PMID- 22052428 TI - The impact of stigma of mental illness in a Canadian community: a survey of patients experiences. AB - We examined stigma experiences and its impact among patients (n = 41) hospitalized for mental illness. We studied their characteristics contributing to the expectation, intensity, and frequency of stigma they could experience. Opinions were compared on the Experiences with the Stigma of Mental Illness scale measuring stigma experiences and impact. There were differences on perceived stigma in: being 19 years or younger at first symptom or treatment, having had one previous psychiatric hospitalizations and having attended one or more outpatient sessions. Those having attended outpatient sessions, being previously hospitalized or younger suffered more impact. PMID- 22052429 TI - Transformational leadership moderates the relationship between emotional exhaustion and turnover intention among community mental health providers. AB - Public sector mental health care providers are at high risk for burnout and emotional exhaustion which negatively affect job performance and client satisfaction with services. Few studies have examined ways to reduce these associations, but transformational leadership may have a positive effect. We examine the relationships between transformational leadership, emotional exhaustion, and turnover intention in a sample of 388 community mental health providers. Emotional exhaustion was positively related to turnover intention, and transformational leadership was negatively related to both emotional exhaustion and turnover intention. Transformational leadership moderated the relationship between emotional exhaustion and turnover intention, indicating that having a transformational leader may buffer the effects of providers' emotional exhaustion on turnover intention. Investing in transformational leadership development for supervisors could reduce emotional exhaustion and turnover among public sector mental health providers. PMID- 22052430 TI - The impact of Tourette Syndrome in adults: results from the Tourette Syndrome impact survey. AB - Chronic tic disorders (CTD) are characterized by motor and/or vocal tics. Existing data on the impact of tics in adulthood is limited by small, treatment seeking samples or by data aggregated across adults and children. The current study explored the functional impact of tics in adults using a nationwide sample of 672 participants with a self-reported CTD. The impact of tics on physical, social, occupational/academic, and psychological functioning was assessed. Results suggested mild to moderate functional impairment and positive correlations between impairment and tic severity. Notable portions of the sample reported social or public avoidance and experiences of discrimination resulting from tics. Compared to previously reported population norms, participants had more psychological difficulties, greater disability, and lower quality of life. The current study suggests that CTDs can adversely impact functioning in adults and highlights the need for clinical interventions and systemic efforts to address tic-related impairments. PMID- 22052431 TI - Nuclear medicine, scientific publishing and the era of cost containment. PMID- 22052432 TI - Report on stage III Pig-a mutation assays using benzo[a]pyrene. AB - Genotoxicity assays were conducted on rats treated with benzo[a]pyrene (BaP) as part of Stage III of a validation study on the Pig-a gene mutation assay. Assays were performed at the U.S. FDA-NCTR and Bayer-Germany. Starting on Day 1, groups of five 6- to 7-week-old male Fischer 344 (F344, used at FDA-NCTR) and Han Wistar rats (Bayer) were given 28 daily doses of 0, 37.5, 75, or 150 mg/kg BaP; blood was sampled on Days -1, 4, 15, 29, and 56. Pig-a mutant frequencies were determined on Days -1, 15, 29, and 56 in total red blood cells (RBCs) and reticulocytes (RETs) as RBC(CD59-) and RET(CD59-) frequencies; percent micronucleated-RETs (%MN-RET) were measured on Days 4 and 29. RBC(CD59-) and RET(CD59-) frequencies increased in a dose- and time-dependent manner, producing significant increases by Day 29 in both rat models. The responses for RETs were stronger than those for RBCs, and the responses in F344 rats were stronger than in Han Wistar rats. BaP also produced significant increases in %MN-RET frequency at Days 4 and 29, with the responses being greater in F344 than Han Wistar rats. The overall findings were consistent with those of the reference laboratory using Han Wistar rats. Finally, mutation assays performed on splenocytes from Day 56 F344 rats indicated that BaP mutant frequencies were three to fivefold higher for the Hprt gene than the Pig-a gene. The results indicate that the Pig-a RET and RBC assays are reproducible, transferable, and show promise for integrating gene mutation into 28-day repeat-dose studies. PMID- 22052433 TI - Interlaboratory Pig-a gene mutation assay trial: Studies of 1,3-propane sultone with immunomagnetic enrichment of mutant erythrocytes. AB - An international collaborative trial was established to systematically investigate the merits and limitations of a rat in vivo Pig-a gene mutation assay. The product of this gene is essential for anchoring CD59 to the plasma membrane, and mutations in this gene are identified by flow cytometric quantification of circulating erythrocytes without cell surface CD59 expression. Initial interlaboratory data from rats treated with several potent mutagens have been informative, but the time required for those flow cytometric analyses (~20 min per sample) limited the number of cells that could be interrogated for the mutant phenotype. Thus, it was desirable to establish a new higher throughput scoring approach before expanding the trial to include weak mutagens or nongenotoxicants. An immunomagnetic column separation method that dramatically increases analysis rates was therefore developed (Dertinger et al. [2011]: Mutat Res 721:163-170). To evaluate this new method for use in the international collaborative trial, studies were conducted to determine the mutagenic response of male Sprague Dawley rats treated for 3 or 28 consecutive days with several doses of 1,3-propane sultone (1,3-PS). Pig-a mutant frequencies were measured over a period of several weeks and were supplemented with another indicator of genetic toxicity, peripheral blood micronucleated reticulocyte (MN-RET) counts. 1,3-PS was found to increase Pig-a mutation and MN-RET frequencies in both 3- and 28-day study designs. While the greatest induction of MN-RETs was observed in the 3-day study, the highest Pig-a responses were found with 28-days of treatment. Pig-a measurements were acquired in approximately one-third the time required in the original method, while the number of erythrocyte and reticulocyte equivalents analyzed per sample were increased by factors of 100 and 10, respectively. The data strongly support the value of using the immunomagnetic separation technique for enumerating Pig-a mutation frequencies. These results also demonstrate that the ongoing international trial will benefit from the inclusion of studies that are based on both acute and protracted repeat dosing schedules in conjunction with the acquisition of longitudinal data, at least until more data have been accumulated. PMID- 22052434 TI - Likelihood-based concordance tests for analysis of ascertained twin pair multinomial data. AB - The classic twin model design has a wide application in human genetics. Under the assumption that nongenetic effects are shared to the same degree by monozygotic (MZ) and dizygotic (DZ) twin pairs, a test of the equality of casewise concordances between MZ and DZ twins provides a clue to the influence of genetic and environmental factors on a disease. The casewise concordance is the conditional probability that given that one member of a twin pair is affected, the other is also affected. When disease prevalence is low or cost-effectiveness is considered, collection of twin pairs by ascertainment for performing casewise concordance analysis is required. In this article, by defining an overall casewise concordance parameter, several likelihood-based tests, such as likelihood ratio test LR, score test Score, the usual Wald test Wald and an alternative Wald test WaldA are investigated for a test of the equality of concordances between ascertained MZ and DZ twin pairs under multinomial models. Simulation studies were conducted for data with small sample sizes. The results show that the type I error rates and power of LR and Score are stable only when the overall casewise concordances are not extremely small or large. The Wald has higher power performance in most cases but would slightly inflate type I error rates; the WaldA is the most robust and recommended approach. PMID- 22052435 TI - Spectroscopic, morphological, and mechanistic investigation of the solvent promoted aggregation of porphyrins modified in meso-positions by glucosylated steroids. AB - Solvent-driven aggregation of a series of porphyrin derivatives was studied by UV/Vis and circular dichroism spectroscopy. The porphyrins are characterised by the presence in the meso positions of steroidal moieties further conjugated with glucosyl groups. The presence of these groups makes the investigated macrocycles amphiphilic and soluble in aqueous solvent, namely, dimethyl acetamide/water. Aggregation of the macrocycles is triggered by a change in bulk solvent composition leading to formation of large architectures that express supramolecular chirality, steered by the presence of the stereogenic centres on the periphery of the macrocycles. The aggregation behaviour and chiroptical features of the aggregates are strongly dependent on the number of moieties decorating the periphery of the porphyrin framework. In particular, experimental evidence indicates that the structure of the steroid linker dictates the overall chirality of the supramolecular architectures. Moreover, the porphyrin concentration strongly affects the aggregation mechanism and the CD intensities of the spectra. Notably, AFM investigations reveal strong differences in aggregate morphology that are dependent on the nature of the appended functional groups, and closely in line with the changes in aggregation mechanism. The suprastructures formed at lower concentration show a network of long fibrous structures spanning over tens of micrometres, whereas the aggregates formed at higher concentration have smaller rod-shaped structures that can be recognised as the result of coalescence of smaller globular structures. The fully steroid substituted derivative forms globular structures over the whole concentration range explored. Finally, a rationale for the aggregation phenomena was given by semiempirical calculations at the PM6 level. PMID- 22052436 TI - Lessons learnt from the recent tsunami in Japan: necessity of epidemiological evidence to strengthen community-based preparation and emergency response plans. PMID- 22052437 TI - Bioresolution of benzyl glycidyl ether using whole cells of Bacillus alcalophilus. AB - The incubation of whole Bacillus alcalophilus cells grown on a mineral supplemented medium (MSM) containing 1% (w/v) sucrose as carbon source, 1.2% (w/v) tryptone as nitrogen source at pH 6.5 and temperature 30 degrees C in 24 h kinetically resolved benzyl glycidyl ether (1 mg/ml) to provide (S)-benzyl glycidyl ether with 30% ee and (R)-3-benzyloxypropane-1,2-diol with 40% ee. PMID- 22052438 TI - Cryptotanshinone down-regulates androgen receptor signaling by modulating lysine specific demethylase 1 function. AB - Development and progression of prostate cancer are intimately associated with androgen receptor (AR) signaling. The emergence of hormone-refractory prostate cancer and consequent failure of conventional androgen deprivation therapies make it necessary to bypass hormonal resistance by targeting the same signaling pathway at new intervention points. In our study, we showed that cryptotanshinone inhibited the growth of AR-positive prostate cancer cells, suggesting that cryptotanshinone affected AR function. Cryptotanshinone also profoundly inhibited the transcriptional activity of AR and suppressed the expression of several AR target genes at the mRNA and the protein levels. At the molecular level, cryptotanshinone disrupted the interaction between AR and lysine-specific demethylase 1 (LSD1), and inhibited the complex of AR and LSD1 to the promoter of AR target genes without affecting the protein degradation and translocation of AR. Cryptotanshinone increased the mono-methyl and di-methylation of Histone H3 lysine 9 (H3K9), a repressive histone marker which is demethylated and activated by LSD1. These data suggest that cryptotanshinone functions via inhibition of LSD1, a protein that promotes AR-dependent transcriptional activity via derepression of H3K9. In summary, we describe a novel mechanism whereby cryptotanshinone down-regulates AR signaling via functional inhibition of LSD1 mediated demethylation of H3K9 and represses the transcriptional activity of AR. Our data suggest that cryptotanshinone can be developed as a potential therapeutic agent for prostate cancer. PMID- 22052439 TI - Remote discovery of an asymptomatic bowel perforation by a mid-urethral sling. AB - Bowel perforation is a rare complication of mid-urethral sling procedures and is usually reported shortly after the surgery. We report a remotely discovered asymptomatic bowel injury found at the time of subsequent surgery. The patient with a history of several prior pelvic surgeries underwent an uneventful retropubic mid-urethral sling placement. Five years later, during an abdominal sacrocolpopexy procedure, mesh from the mid-urethral sling was found perforating the wall of the cecum and fixating it to the right pelvic sidewall. Cecal wedge resection was performed to excise the sling mesh. Asymptomatic bowel perforation by mid-urethral sling mesh has not been previously reported. Pelvic and abdominal surgeons should be aware of the possibility of finding this injury in patients with prior sling surgeries. PMID- 22052440 TI - Nocturia * disturbed sleep: a review. AB - In this article, we provide a concise review of the literature on nocturia and its interference with sleep and, consequently, on quality of life. There are few studies addressing the possible influences of nocturia on sleep disruption. Nocturia is a potential contributor to sleep disorders because affected individuals experience nonrestorative sleep due to frequent interruptions. We also attempted to determine whether individuals with nocturia wake to urinate or, alternately, urinate because they are awake. This review attempts to outline this specific association by examining the possible interactions with other medical conditions and the pathophysiology and prevalence. Most studies have observed a higher prevalence among women; however, the impact on quality of life is higher in men. Nocturia is not necessarily associated with natural aging. The exploration of these topics provides information to clarify the implications of nocturia on sleep, sleep disruption, and other related consequences. Additional evidence is still required to address the question of whether nocturia leads to disordered sleep or whether disordered sleep leads to nocturia. PMID- 22052441 TI - Validation of Persian version of the Prolapse Quality-of-Life questionnaire (P QOL). AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the validity and reliability of a Persian translation of the Prolapse Quality-of-Life (P-QOL) questionnaire in women with pelvic organ prolapse (POP). METHODS: One hundred and twenty-four women with POP symptoms and 125 asymptomatic women were studied. The asymptomatic group was used for discriminant validity. RESULTS: Seventy-two percent (89/124) of the symptomatic women had stage >= 2 POP while 86% (108/125) of the asymptomatic women had a stage <2 POP. All domains of the Persian P-QOL have a Cronbach's alpha coefficient greater than 0.7 (0.78-0.97) and were significantly different between symptomatic and asymptomatic women indicating a good discriminant validity (<0.01). The test-retest reliability confirmed a highly significant correlation. All items of P-QOL questionnaire correlated significantly with the objective vaginal examination findings (construct validity) except for personal relationship and emotions. CONCLUSION: The Persian version of the P-QOL is a valid and reliable tool to assess QOL of women with POP. PMID- 22052442 TI - Organocatalytic enantioselective amination of Morita-Baylis-Hillman carbonates with masked ammonia: a facile method for the synthesis of unprotected alpha methylene-beta-amino esters. PMID- 22052443 TI - Modified type III cordectomy to improve voice outcomes after transoral laser microsurgery for early glottic canser. AB - BACKGROUND: We proposed a modified type III cordectomy for the treatment of early glottic cancer that removed the upper part of the vocalis muscle to improve glottic closure and voice outcomes. METHODS: Twenty-two patients with early glottic cancer underwent type III cordectomy, including 9 classical (proposed by European Laryngological Society) and 13 modified resections. Multidimensional voice evaluations were performed. RESULTS: Voice parameters including GRBAS (overall grade [G], roughness of the voice [R], breathiness [B], asthenicity [A], and strain [S]), jitter, shimmer, noise-to-harmonic ratio, maximum phonation time, voice handicap index-functional, physical, and total scores were better in modified resection. Eleven patients (85%) had complete glottic closure in modified resection and 3 (33%) in classical resection (p = .026). Only 2 patients had tumor recurrence, 1 (8%) in the modified resection and 1 (11%) in the classical resection group (p = 1.000). CONCLUSIONS: Modified type III cordectomy proved to be an oncologically safe method. The voice outcomes were better than those in patients who underwent classical type III cordectomy. PMID- 22052444 TI - Application of biomarkers to clinical trials in systemic sclerosis. AB - Important clinical advances in the treatment of systemic sclerosis have been made, yet fibrotic disease remains largely untreatable. Optimal design of clinical trials to test new therapeutics for fibrotic disease features has suffered from dual difficulties in patient selection and patient evaluation. Patient selection for entry into trials for treatment of interstitial lung disease and/or skin fibrosis is challenged by the natural history of the disease, which stabilizes in some patients while relentlessly progressing in others, and our lack of good clinical markers to distinguish between these trajectories. Patient evaluation is made difficult, particularly in skin disease, by the inherent difficulty in quantifying the extent of disease. Biomarkers hold the potential to solve many of these problems as surrogate outcome measures and as markers for disease progression. Identified biomarkers may have the potential to graduate to surrogate outcome singly or, more likely, in combination. Predictive biomarkers are still largely unknown. PMID- 22052445 TI - Successes and failures in producing attentional object-based cueing effects. AB - Over 30 years of research using Posner's spatial cueing paradigm has shown that selective attention operates on representations of spatial locations, leading to space-based theories of attention. Manipulations of stimuli and methods have shown this paradigm to be sensitive to several types of object-based representations-providing evidence for theories incorporating object-based attentional selection. This paper critically evaluates the evidence demanding object-based explanations that go beyond positing spatial representations alone, with an emphasis on identifying and interpreting successes and failures in obtaining object-based cueing effects. This overview of current evidence is used to generate hypotheses regarding critical factors in the emergence and influence of object representations-their generation, strength, and maintenance-in the modulation of object-based facilitatory and inhibitory cueing effects. PMID- 22052446 TI - Prevalence and distribution of adenomas in black Americans undergoing colorectal cancer screening. AB - BACKGROUND: The American College of Gastroenterology recommends colorectal cancer (CRC) screening for average-risk black Americans ages 45-49. This is based on this group's younger age for the development of adenomas and CRC. Our purpose was to determine the yield of CRC screening in average-risk black Americans including those 65 years. Aging-related atrial remodeling with fibrosis, dilation and mitochondrial DNA mutations predispose elderly patients to AF. Current management options for AF, including rate control and anticoagulation therapy, can be successfully applied to the elderly population. New antiarrhythmic and anticoagulation medications such as dronedarone and dabigatran, respectively, can impact the approach to therapy in the elderly. Non-pharmacological options such as catheter-based ablation have also gained prominence and have been incorporated into the guidelines for management of AF. However, more trials in the elderly and very elderly segments are needed to clarify the safety and long-term efficacy of the new treatment options. PMID- 22052474 TI - Syringomyelia associated with arachnoid septum at the craniovertebral junction, contradicting the currently prevailing theory of syringomyelia formation. AB - Despite a number of various hypotheses in the literature, the pathophysiology of syringomyelia is still not well understood. In this article, we report two cases of cervical syringomyelia not associated with Chiari I malformation. Both cases had a septum-like structure in the subarachnoid space on the dorsal side of the cord at the craniovertebral junction. Cardiac-gated phase-contrast cine-mode magnetic resonance imaging (MRI) demonstrated decreased cerebrospinal fluid (CSF) flow on the dorsal side of the spinal cord. Surgical excision of this septum, restoring the CSF flow, resulted in a prompt reduction of the syrinx size in both cases. Findings in these cases contradict the currently prevailing hypothesis of syrinx formation that postulate that the piston-like movement of the cerebellar tonsils enhance the pulsatile CSF flow in the spinal subarachnoid space, driving the CSF into the syrinx through the perivascular space of Virchow and Robin. The authors propose that a mechanism based on the decreased pulsatile CSF flow in the spinal subarachnoid space will be more suitable as a hypothesis in studying the pathophyisiology of syringomyelia. These cases also provide an important lesson in managing the patients with syringomyelia not associated with Chiari I malformation. PMID- 22052475 TI - Highly enantioselective synthesis of tertiary boronic esters and their stereospecific conversion to other functional groups and quaternary stereocentres. AB - Organoboron compounds are useful in asymmetric synthesis. We have developed an efficient methodology for the highly enantioselective synthesis of tertiary boronic esters from the corresponding secondary benzylic alcohols. Further stereospecific transformations of the boronic ester moiety are described including the preparation of tertiary alcohols, C-tertiary amines and tertiary arylalkanes. Several homologations of tertiary boronic esters have also been developed for the construction of quaternary stereocentres. PMID- 22052476 TI - Modelling complex biological systems using an agent-based approach. AB - Many of the complex systems found in biology are comprised of numerous components, where interactions between individual agents result in the emergence of structures and function, typically in a highly dynamic manner. Often these entities have limited lifetimes but their interactions both with each other and their environment can have profound biological consequences. We will demonstrate how modelling these entities, and their interactions, can lead to a new approach to experimental biology bringing new insights and a deeper understanding of biological systems. PMID- 22052477 TI - Subsidence of a cementless femoral component influenced by body weight and body mass index. AB - PURPOSE: This trial was designed to evaluate the impact of physical characteristics such as body mass index, body weight and height on distal stem migration of a cementless femoral component, as the influence of obesity on the outcome of THA is still debated in literature and conflicting results have been found. METHODS: In this retrospective cohort study, migration patterns for 102 implants were analysed using the Einzel-Bild-Roentgen-Analyse (EBRA-FCA, femoral component analysis). In all cases the Vision 2000 stem was implanted and combined with the Duraloc acetabular component (DePuy, Warsaw, Indiana). RESULTS: The mean follow-up was 93 months. EBRA-FCA evaluations revealed a mean subsidence of 1.38 mm after two years, 2.06 mm after five and 2.24 mm after seven years. Five stems loosened aseptically. Correlation between increased migration over the whole period and aseptic loosening was highly significant (p < 0.001). Surgical technique had a significant influence on migration and stem stability (p = 0.002) but physical patient characteristics such as body weight over 75 kg and height over 165 cm also significantly influenced stem subsidence towards progressive migration (p = 0.001, p < 0.001). However, a high BMI did not trigger progressive stem migration (p = 0.87). Being of the male gender raised the odds for increased migration (p = 0.03). CONCLUSION: Physical characteristics such as body weight and height showed significant influence on migration patterns of this cementless femoral component. The operating surgeon should be aware that body weight above 75 kg and height over 165 cm may trigger increased stem migration and the surgeon should aim to fit these prostheses as tightly as possible. However this study demonstrates that a high BMI does not trigger progressive stem migration. Further investigations are needed to confirm our findings. PMID- 22052478 TI - Could the use of bone morphogenetic proteins in fracture healing do more harm than good to our patients? PMID- 22052479 TI - Follow-up of thirty-three computed-tomography-guided percutaneous radiofrequency thermoablations of osteoid osteoma. AB - PURPOSE: This study aimed to determine the mid- and long-term success and complication rates of radiofrequency ablation (RFA) in treatment of osteoid osteoma (OO). Furthermore we were interested in the value of bone biopsy when using a core-drill before the radiofrequency ablation. METHODS: We retrospectively analysed data of 33 patients (33 osteoid osteomas, 22 males, 11 females) who underwent computed-tomography (CT) guided radiofrequency ablation between 1998 and 2005. The patients had a mean age of 20 years (range, five to 50 years). They were monitored for a mean follow-up of 92 months (range, 60-121 months). RESULTS: Lesions were located as follows: 11 cases in the proximal femur, five in the femoral shaft, six in the tibia, one in the calcaneus, two in the metatarsals (second and fourth metatarsals), one in the os cuneiforme mediale, six in the humeral and one in the ulnar shaft. Within the presented time frame 32 of 33 patients were successfully treated and had no more complaints. In one of 33 patients relapse occurred after 28 months and RFA was repeated. There were no complications associated with the procedure. Biopsy obtained prior to thermocoagulation with the help of a core-drill was able to prove diagnosis in all patients (100%). CONCLUSIONS: These results indicate that the presented technique of CT guided RFA combined with the use of a core-drill for biopsy prior to RFA treatment is a highly effective, efficient, minimally invasive and safe method for the treatment of OO, yielding a success rate of 97% combined with a 100% histological verification of the diagnosis after a minimum follow-up period of five years. PMID- 22052481 TI - Total synthesis of (-)-brevenal: a streamlined strategy for practical synthesis of polycyclic ethers. AB - We describe a streamlined strategy for the practical synthesis of trans-fused polycyclic ethers and its application to a concise total synthesis of (-) brevenal, a new pentacyclic polyether natural product with intriguing biological activities. The B-, D-, and E-rings were constructed by TEMPO/PhI(OAc)(2) mediated oxidative lactonization of the corresponding 1,6-diols, with minimal need for manipulation of oxygen functionalities. The B- and E-ring lactones were appropriately functionalized by Suzuki-Miyaura coupling of lactone-derived enol phosphates and subsequent stereoselective hydroboration. The A-ring was formed by our mixed thioacetalization methodology. The AB- and DE-ring fragments were assembled through Suzuki-Miyaura coupling, and the C-ring was forged in the same manner as that for the A-ring. More than two grams of the pentacyclic polyether core of (-)-brevenal have been synthesized by the synthetic route developed in this study. PMID- 22052482 TI - Binding techniques to study the allosteric energy cycle. AB - Thermodynamic principles of cooperativity and allostery have long been used as a starting point to begin understanding the interplay between ligand binding events. Understanding the nature of allosteric effects requires an experimental technique that can be used to quantify ligand binding energies and simultaneously give experimental insights into the conformational dynamics at play upon ligand binding. CD spectroscopy provides macroscopic information about the relative secondary and tertiary structures present in a protein. Here, we use this spectroscopic technique with thermal shift assays wherein ligand binding constants can be quantified based on their stabilizing effect against thermally induced protein denaturation. Binding constants for two ligands are used to determine a pairwise coupling free energy which defines the shared energy that favors or opposes binding of the second ligand binding event in an allosteric system. In CD-based thermal shift assays, temperature is the driving force for protein unfolding and can also influence protein conformational dynamics present in the unbound protein or ligand-bound proteins. Dihydrofolate reductase (DHFR) and glutamate dehydrogenase (GDH) are proposed as example test systems. NADP and methotrexate bind DHFR with positive cooperativity. Mammalian GDH exhibits negative cooperativity with respect to binding of NAD and NADPH coenzyme molecules, activation by ADP, and inhibition by GTP. PMID- 22052483 TI - Kinetic trapping of a key hemoglobin intermediate. AB - The complete binding cascade of human hemoglobin consists of a series of partially ligated intermediates. The individual intermediate binding constants cannot be distinguished in O(2) binding curves, however, each constant can be determined from the O(2)-induced change in assembly constant for the alpha(2)beta(2) tetramer from its constituent alphabeta dimers. The characterization of these O(2) binding constants has shown the Hb cascade to be asymmetric in nature, with binding dependent upon the specific distribution of O(2) among the four hemesites. A stopped-flow approach to measuring the dissociation constant of a key doubly ligated intermediate, that in which one dimer is oxygenated and the other is not, is described. The intermediate is transiently formed in the absence of O(2) and then allowed to dissociate in the presence of O(2). The free dimers thus released are trapped by the plasma protein haptoglobin, the rate limiting step being that of tetramer dissociation. The kinetic constant observed for the dissociation of this intermediate confirms the value for its equilibrium O(2) binding constant, previously determined under equilibrium conditions by subzero isoelectric focusing. PMID- 22052484 TI - Allosteric coupling between transition metal-binding sites in homooligomeric metal sensor proteins. AB - Intracellular concentrations of transition metal ions are controlled at the transcriptional level by a panel of metalloregulatory proteins that collectively allow the cell to respond to changes in bioavailable metal concentration to elicit the appropriate cellular response, e.g., upregulation of genes coding for metal export or detoxification proteins in the event of metal excess. These proteins represent a specialized class of allosteric regulators that are ideal for studying ligand-mediated allostery in a comprehensive way due to the size, stability, reactivity, and the spectroscopic properties of transition metal ions as allosteric ligands. In addition to the commonly studied heterotropic regulation of metal binding and DNA binding, many of these proteins exhibit homotropic allostery, i.e., communication between two or more identical metal (ligand) binding sites on an oligomer. This chapter aims to guide the reader through the design and execution of experiments that allow quantification of the thermodynamic driving forces (DeltaG (C), DeltaH (C), and DeltaS (C)) that govern both homotropic and heterotropic allosteric interactions in metal sensor proteins as well as the steps required to remove the influence of complex speciation from the measured parameter values. PMID- 22052485 TI - Studying the allosteric energy cycle by isothermal titration calorimetry. AB - Isothermal titration calorimetry (ITC) is a powerful biophysical technique which allows a complete thermodynamic characterization of protein interactions with other molecules. The possibility of dissecting the Gibbs energy of interaction into its enthalpic and entropic contributions, as well as the detailed additional information experimentally accessible on the intermolecular interactions (stoichiometry, cooperativity, heat capacity changes, and coupled equilibria), make ITC a suitable technique for studying allosteric interactions in proteins. Two experimental methodologies for the characterization of allosteric heterotropic ligand interactions by ITC are described in this chapter, illustrated with two proteins with markedly different structural and functional features: a photosynthetic electron transfer protein and a drug target viral protease. PMID- 22052486 TI - Detecting "silent" allosteric coupling. AB - Using isothermal calorimetry (ITC), we have found one case where a well characterized allosteric activator showed no sign of allostery in its DeltaG degrees of binding to successive sites on multiple subunits and another case where successive binding showed no DeltaG degrees binding allostery but did show large entropy-compensated flip-flopping enthalpy changes. This behavior, which we have termed "isoergonic cooperativity" and others have referred to as "silent coupling" is quite simply explained by basic linkage theory when reactions are considered beyond the DeltaG degrees level. Thus, direct calorimetric determination of all thermodynamic parameters including DeltaH degrees , DeltaS degrees , DeltaG degrees , DeltaC (p) degrees , and d(DeltaC (p) degrees /dt) provides a more informative depiction of a ligand binding event and its consequences than does the mere measurement of DeltaG degrees alone. We further discuss the benefits and limitations of methods that have previously been used to study silent coupling. In particular, ITC is free of the numerous pitfalls inherent in the application of van't Hoff and Arrhenius plots to allosteric phenomena. Aside from having a 30-fold advantage in precision, ITC is capable of measuring changes in enthalpy directly at five more levels of mathematical differentiation than are available to van't Hoff type approaches. PMID- 22052487 TI - Using mutant cycle analysis to elucidate long-range functional coupling in allosteric receptors. AB - Functional coupling of residues that are far apart in space is the quintessential property of allosteric receptors. Data from functional studies of allosteric receptors, such as whole-cell dose-response relations, can be used to determine if mutation to a receptor significantly impacts agonist potency. However, the classification of perturbations as primarily impacting binding or allosteric function is more challenging, often requiring detailed kinetic studies. This protocol describes a simple strategy, derived from mutant cycle analysis, for elucidating long-range functional coupling in allosteric receptors (ELFCAR). Introduction of a gain-of-function reporter mutation, followed by a mutant cycle analysis of the readily measured macroscopic EC(50) values can provide insight into the role of many physically distant targets. This new method should find broad application in determining the functional roles of residues in allosteric receptors. PMID- 22052488 TI - A review of methods used for identifying structural changes in a large protein complex. AB - This chapter explores the structural responses of a massive, hetero-oligomeric protein complex to a single allosteric activator as probed by a wide range of chemical, biochemical, and biophysical approaches. Some of the approaches used are amenable only to large protein targets, whereas others push the limits of their utility. Some of the techniques focus on individual subunits, or portions thereof, while others examine the complex as a whole. Despite the absence of crystallographic data for the complex, the diverse techniques identify and implicate a small region of its catalytic subunit as the master allosteric activation switch for the entire complex. PMID- 22052489 TI - Allosteric mechanisms of G protein-Coupled Receptor signaling: a structural perspective. AB - G protein-Coupled Receptors (GPCRs) use a complex series of intramolecular conformational changes to couple agonist binding to the binding and activation of cognate heterotrimeric G protein (Galphabetagamma). The mechanisms underlying this long-range activation have been identified using a variety of biochemical and structural approaches and have primarily used visual signal transduction via the GPCR rhodopsin and cognate heterotrimeric G protein transducin (G(t)) as a model system. In this chapter, we review the methods that have revealed allosteric signaling through rhodopsin and transducin. These methods can be applied to a variety of GPCR-mediated signaling pathways. PMID- 22052491 TI - Dissecting the linkage between transcription factor self-assembly and site specific DNA binding: the role of the analytical ultracentrifuge. AB - A long-standing goal of biomedical research has been to determine the quantitative mechanisms responsible for gene regulation and transcriptional activation. These events occur through numerous protein-protein and protein-DNA interactions, many of which are allosterically coupled. For systems where highly purified protein is available, analytical ultracentrifugation provides a means to study these linked reactions, allosteric or otherwise. Sedimentation velocity is an ultracentrifugation technique that provides rigorous insight into protein self association, homogeneity, and gross structure. Because self-association is often in dynamic equilibrium with other reactions such as DNA binding, an explicit and independent analysis of each interaction is critical to revealing mechanism. This chapter details a protocol for using sedimentation velocity to dissect the linkage between transcription factor self-association and site-specific DNA binding. PMID- 22052490 TI - Dynamic light scattering to study allosteric regulation. AB - The Escherichia coli ClpA protein, like many AAA+ motor proteins, is allosterically regulated by nucleotide binding. We have combined analytical ultracentrifugation approaches with dynamic light scattering (DLS) to examine the self-association properties and the allosteric linkage of assembly to nucleotide binding. Here we present a protocol for the rapid and precise determination of the diffusion coefficient using DLS measurements in a model-independent fashion. When combined with analytical ultracentrifugation experiments, such an approach can yield a more complete understanding of the hydrodynamic and thermodynamic properties of the system. PMID- 22052492 TI - Fluorescence correlation spectroscopy and allostery: the case of GroEL. AB - Fluorescence correlation spectroscopy (FCS) is an experimental technique in which the equilibrium fluctuations of the fluorescent signal of molecules diffusing through a focused laser beam are measured. An autocorrelation analysis of these fluctuations provides information on dynamic processes, such as allosteric transitions, that the molecules undergo provided that they are fast relative to the diffusion time through the beam. In cases when the dynamics are slow relative to the diffusion time through the beam, FCS curves can yield information about the number of conformational states and their relative populations. Hence, FCS can be used to investigate allosteric systems with either slow or fast dynamics but the type of information gained in these two situations is different.Here, the utility of the FCS technique is exemplified in the case of the single-ring version of the Escherichia coli molecular chaperone GroEL that interconverts with relatively slow dynamics between two allosteric states: a T state with low affinity for ATP and an R state with high affinity for ATP. Thermodynamic analysis suggests that the T-state population should become negligible with increasing ATP concentrations, in conflict with the requirement for conformation cycling, which is essential for the operation of molecular machines. Surprisingly, FCS experiments showed that, even at ATP saturation, ~50% of the molecules still populate the T state at any instance of time, indicating constant out-of-equilibrium cycling between T and R. PMID- 22052493 TI - The morpheein model of allostery: evaluating proteins as potential morpheeins. AB - An equilibrium mixture of alternate quaternary structure assemblies can form a basis for allostery. The morpheein model of allostery is a concerted dissociative model that describes an equilibrium of alternate quaternary structure assemblies whose architectures are dictated by alternate conformations in the dissociated state. Kinetic and biophysical anomalies that suggest that the morpheein model of allostery applies for a given protein of interest are briefly described. Two methods are presented for evaluating proteins as potential morpheeins. One is a subunit interchange method that uses chromatography, dialysis, and mass spectroscopy to monitor changes in multimer composition. The other is a two dimensional native gel electrophoresis method to monitor ligand-induced changes in an equilibrium of alternate multimeric assemblies. PMID- 22052494 TI - Combining NMR and molecular dynamics studies for insights into the allostery of small GTPase-protein interactions. AB - Combinations of experimentally derived data from nuclear magnetic resonance spectroscopy and analyses of molecular dynamics trajectories increasingly allow us to obtain a detailed description of the molecular mechanisms by which proteins function in signal transduction. This chapter provides an introduction into these two methodologies, illustrated by example of a small GTPase-effector interaction. It is increasingly becoming clear that new insights are provided by the combination of experimental and computational methods. Understanding the structural and protein dynamical contributions to allostery will be useful for the engineering of new binding interfaces and protein functions, as well as for the design/in silico screening of chemical agents that can manipulate the function of small GTPase-protein interactions in diseases such as cancer. PMID- 22052495 TI - Hydrogen-deuterium exchange study of an allosteric energy cycle. AB - Elucidation of mechanisms of energy transduction through macromolecules in allosteric systems requires application of a broad range of techniques and approaches. High-resolution structures of the end states in an allosteric system provide invaluable clues about allosteric mechanism. Thermodynamic and kinetic studies reveal the rules that govern the transitions between states in the system. Acquisition of detailed molecular level information about allosteric mechanism requires interrogation of the structural and dynamic properties of both intermediates and end states in the allosteric cycle. Many experimental and computational tools have been developed to probe allostery. Among these are hydrogen-deuterium exchange detected by either NMR spectroscopy or mass spectrometry. This article provides a detailed description of application of hydrogen exchange detected by mass spectrometry (HDX-MS) to investigate an allosteric system. PMID- 22052496 TI - Ensemble properties of network rigidity reveal allosteric mechanisms. AB - The distance constraint model (DCM) is a unique computational modeling paradigm that integrates mechanical and thermodynamic descriptions of macromolecular structure. That is, network rigidity calculations are used to account for nonadditivity within entropy components, thus restoring the utility of free energy decomposition. The DCM outputs a large number of structural characterizations that collectively allow for quantified stability-flexibility relationships (QSFR) to be identified. In this review, we describe the theoretical underpinnings of the DCM and introduce several common QSFR metrics. Application of the DCM across protein families highlights the sensitivity within the set of protein structure residue-to-residue couplings. Further, we have developed a perturbation method to identify putative allosteric sites, where large changes in QSFR upon rigidification (mimicking ligand-binding) detect sites likely to invoke allosteric changes. PMID- 22052497 TI - An in vivo approach to isolating allosteric pathways using hybrid multimeric proteins. AB - Hybrid tetramers of Escherichia coli phosphofructokinase (EC 2.7.1.11; EcPFK) have been used to dissect the complicated allosteric interactions within the native tetramer. The method used previously to generate hybrids in vitro involves dissociation of the parent proteins with KSCN followed by re-association as KSCN is removed via dialysis. However, this procedure is time consuming and is plagued with low hybrid yields. Consequently, we have attempted to produce hybrids more quickly and with potentially higher yields in vivo by co-expressing the parental EcPFK protein in E. coli. Wild-type EcPFK gene was cloned into pALTER-Ex2 and pALTER-1, respectively. Site-directed mutagenesis was performed to make mutant EcPFK gene in pALTER-1. Since each vector has a different origin of replication and antibiotic selection marker, we were able to co-transform both plasmids to competent E. coli cells. Following an affinity purification column, anion exchange chromatography was used to separate the five hybrid species (4:0, 3:1, 2:2, 1:3, 0:4). While all five hybrid species were obtained, the amount 1:3 and 0:4 hybrids were very small. By changing the expression vector for the mutant EcPFK protein from pALTER-1 to pALTER-Ex1 and the charge-tag mutations from K2E/K3E to K90E/K91E, the yield of 1:3 hybrid was substantially increased. The in vivo method does increase the yield of the hybrids produced while decreasing the time required for their isolation. PMID- 22052499 TI - Allosteric regulation of human liver pyruvate kinase by peptides that mimic the phosphorylated/dephosphorylated N-terminus. AB - An advantage of studying allosteric regulation over covalent modification is that allostery allows the experimentalist to vary the concentration of effector, thereby allowing independent quantification of effector binding and allosteric coupling. In turn, this capacity allows the use of effector analogues to determine which regions of the effector contribute to effector binding and which contribute to allosteric regulation. Like many other proteins, human liver pyruvate kinase (hL-PYK) is regulated by phosphorylation. The phosphorylation of hL-PYK occurs on Ser12 of the N-terminus. Phosphorylation appears to interrupt an interaction (distant from the active site) between the N-terminus and the main body of the protein. Since this interaction increases the affinity of hL-PYK for the substrate (phosphoenolpyruvate, PEP), phosphorylation-dependent interruption of the N-terminus/main-body interaction results in an antagonism of PEP binding. Due to the advantages of studying an allosteric system, we detail a protocol to express and purify N-terminal peptides of hL-PYK using a SUMO-fusion system. We further demonstrate that these peptides act as allosteric regulators that modulate the affinity of hL-PYK for PEP. PMID- 22052498 TI - Mutations in the GABAA receptor that mimic the allosteric ligand etomidate. AB - Etomidate is a hydrophobic molecule, a potent general anesthetic, and the best understood drug in this group. Etomidate's target molecules are GABA(A) receptors, its site of action has been identified with photolabeling, and a quantitative allosteric coagonist model has emerged for etomidate effects on GABA(A) receptors. We have shown that when methionine residues that are thought to be adjacent to the etomidate site are mutated to tryptophan, that the bulky hydrophobic side-chains alter mutant GABA(A) receptor function in ways that mimic the effects of etomidate binding to wild-type receptors. Furthermore, these mutations reduce receptor modulation by etomidate. Both of these observations support the hypothesis that these methionine residues form part of the etomidate binding pocket. PMID- 22052500 TI - In silico-screening approaches for lead generation: identification of novel allosteric modulators of human-erythrocyte pyruvate kinase. AB - Identification of allosteric binding site modulators have gained increased attention lately for their potential to be developed as selective agents with a novel chemotype and targeting perhaps a new and unique binding site with probable fewer side effects. Erythrocyte pyruvate kinase (R-PK) is an important glycolytic enzyme that can be pharmacologically modulated through its allosteric effectors for the treatment of hemolytic anemia, sickle-cell anemia, hypoxia-related diseases, and other disorders arising from erythrocyte PK malfunction. An in silico screening approach was applied to identify novel allosteric modulators of pyruvate kinase. A small-molecules database of the National Cancer Institute (NCI), was virtually screened based on structure/ligand-based pharmacophore. The virtual screening campaign led to the identification of several compounds with similar pharmacophoric features as fructose-1,6-bisphosphate (FBP), the natural allosteric activator of the kinase. The compounds were subsequently docked into the FBP-binding site using the programs FlexX and GOLD, and their interactions with the protein were analyzed with the energy-scoring function of HINT. Seven promising candidates were obtained from the NCI and subjected to kinetics analysis, which revealed both activators and inhibitors of the R-isozyme of PK (R PK). PMID- 22052501 TI - Identification of allosteric-activating drug leads for human liver pyruvate kinase. AB - There is a growing appreciation of the beneficial attributes of allosteric drugs. However, the development of this special class of drugs has in large part been via serendipitous findings from high-throughput screens of drug libraries. Limited success at deliberately identifying allosteric drugs may be due to a focus on enzyme inhibitors, a parallel to the historic focus on competitive inhibitors. In contrast to inhibition, activation of an enzyme by a small molecule can only occur through a limited number of mechanisms, mainly allosteric regulation. Activation of human liver pyruvate kinase (hL-PYK) in an effort to create a glycolytic/gluconeogenic futile cycle is one potential mechanism to counteract hyperglycemia. Using hL-PYK, we demonstrate the potential of drug library screens to identify allosteric-activator drug leads. PMID- 22052502 TI - A critical evaluation of correlated mutation algorithms and coevolution within allosteric mechanisms. AB - The notion of using the evolutionary history encoded within multiple sequence alignments to predict allosteric mechanisms is appealing. In this approach, correlated mutations are expected to reflect coordinated changes that maintain intramolecular coupling between residue pairs. Despite much early fanfare, the general suitability of correlated mutations to predict allosteric couplings has not yet been established. Lack of progress along these lines has been hindered by several algorithmic limitations including phylogenetic artifacts within alignments masking true covariance and the computational intractability of consideration of more than two correlated residues at a time. Recent progress in algorithm development, however, has been substantial with a new generation of correlated mutation algorithms that have made fundamental progress toward solving these difficult problems. Despite these encouraging results, there remains little evidence to suggest that the evolutionary constraints acting on allosteric couplings are sufficient to be recovered from multiple sequence alignments. In this review, we argue that due to the exquisite sensitivity of protein dynamics, and hence that of allosteric mechanisms, the latter vary widely within protein families. If it turns out to be generally true that even very similar homologs display a wide divergence of allosteric mechanisms, then even a perfect correlated mutation algorithm could not be reliably used as a general mechanism for discovery of allosteric pathways. PMID- 22052503 TI - The advantage of global fitting of data involving complex linked reactions. AB - In this chapter, we demonstrate the advantage of the simultaneous multicurve nonlinear least-squares analysis over that of the conventional single-curve analysis. Fitting results are subjected to thorough Monte Carlo analysis for rigorous assessment of confidence intervals and parameter correlations. The comparison is performed on a practical example of simulated steady-state reaction kinetics complemented with isothermal calorimetry (ITC) data resembling allosteric behavior of rabbit muscle pyruvate kinase (RMPK). Global analysis improves accuracy and confidence limits of model parameters. Cross-correlation between parameters is also reduced with accompanying enhancement of the model testing power. This becomes especially important for validation of models with "difficult" highly cross-correlated parameters. We show how proper experimental design and critical evaluation of data can improve the chance of differentiating models. PMID- 22052504 TI - Predicting binding sites by analyzing allosteric effects. AB - This chapter describes a method for analyzing the allosteric influence of molecular interactions on protein conformational distributions. The method, called Dynamics Perturbation Analysis (DPA), generally yields insights into allosteric effects in proteins and is especially useful for predicting ligand binding sites. The use of DPA for binding site prediction is motivated by the following allosteric regulation hypothesis: interactions in native binding sites cause a large change in protein conformational distributions. Here, we review the reasoning behind this hypothesis, describe the math behind the method, and present a recipe for predicting binding sites using DPA. PMID- 22052505 TI - Effects of long-term fertilization on the diversity of bacterial mercuric reductase gene in a Chinese upland soil. AB - Soil mercury (Hg) pollution has received considerable attention due to its neurotoxin effects and its potential risk to food safety. The microbial transformation of Hg plays a key role in reducing Hg toxicity by the mercuric reductase (MerA) conferred by genes arranged in the mer operon. This study investigated the effects of long-term fertilization on the diversity of bacterial mercuric reductase gene (merA), which specify the reduction of ionic Hg2+ to the volatile elemental form Hg0, in an agricultural soil with relatively high Hg content. The soil samples were collected from different treatments, including control without fertilizer (CK), fertilizer nitrogen (N), combined fertilizers (NPK) of N, phosphorus (P) and potassium (K), and NPK plus organic manure (NPK + OM). The merA gene diversity patterns were analyzed based on the merA clone libraries and sequencing measurements. Results showed that the merA gene diversity was influenced by soil variables depending on the fertilization practices. In particular, NH4+ and NO3- contents had strong effect on the merA gene diversity pattern both in the N and NPK treatments, whereas the merA gene diversity pattern in NPK + OM treatment was distinctly influenced by the contents of organic matter, available P and K. These results suggested that long-term fertilization had significant influences on merA gene diversity, which could be helpful to understand the Hg reduction process and potentially serve microbial remediation of Hg contaminated soil. PMID- 22052507 TI - Smoking cessation 1 year poststroke and damage to the insular cortex. AB - BACKGROUND AND PURPOSE: Hospitalization as a result of stroke provides an opportunity to stop smoking that is often not taken up. The present study analyzes sociodemographic, psychological, and lesion-related variables to identify associated factors for smoking cessation during the first year after stroke. METHODS: We conducted a prospective longitudinal study with a 1-year follow-up of a cohort of 110 patients with acute stroke who were smokers at the time of diagnosis and were admitted consecutively between January 2005 and July 2007. RESULTS: On hospital release, 69.1% had given up smoking but at 1 year, only 40% had stopped smoking. Of the 110 patients, 27 (24.5%) had an acute stroke lesion in the insular cortex, of which 19 (70.3%) were nonsmokers at 1 year. Strongly associated factors in giving up smoking were the location of the lesion in the insular cortex (OR, 5.42; 95% CI, 1.95-15.01; P=0.001) and having the intention of giving up before the stroke, comparing precontemplating patients (without intention of giving up in the near future) with contemplating and prepared patients (intention of stopping in the near future; OR, 7.29; 95% CI, 1.89-28.07; P=0.004). CONCLUSIONS: Of patients with stroke who were smokers, only 4 of 10 patients had stopped smoking 1 year after admission. Our results show that the variables best predicting smoking cessation in patients with a stroke diagnosis 1 year after hospital discharge are insular damage and the prestroke intention to stop. PMID- 22052506 TI - Bace1 processing of NRG1 type III produces a myelin-inducing signal but is not essential for the stimulation of myelination. AB - Myelin sheath thickness is precisely adjusted to axon caliber, and in the peripheral nervous system, neuregulin 1 (NRG1) type III is a key regulator of this process. It has been proposed that the protease BACE1 activates NRG1 dependent myelination. Here, we characterize the predicted product of BACE1 mediated NRG1 type III processing in transgenic mice. Neuronal overexpression of a NRG1 type III-variant, designed to mimic prior cleavage in the juxtamembrane stalk region, induces hypermyelination in vivo and is sufficient to restore myelination of NRG1 type III-deficient neurons. This observation implies that the NRG1 cytoplasmic domain is dispensable and that processed NRG1 type III is sufficient for all steps of myelination. Surprisingly, transgenic neuronal overexpression of full-length NRG1 type III promotes hypermyelination also in BACE1 null mutant mice. Moreover, NRG1 processing is impaired but not abolished in BACE1 null mutants. Thus, BACE1 is not essential for the activation of NRG1 type III to promote myelination. Taken together, these findings suggest that multiple neuronal proteases collectively regulate NRG1 processing. PMID- 22052508 TI - How does number of risk factors affect prognosis in young patients with ischemic stroke? AB - BACKGROUND AND PURPOSE: We aimed to explore clinical features of young patients with ischemic stroke with no traditional vascular risk factors and to assess the impact of risk factor counts on outcomes. METHODS: We included 990 patients aged 15 to 49 years with first-ever ischemic stroke followed for a mean of 9.0 +/- 3.8 years (survivors). Risk factors were categorized as well-documented and less well documented. Outcome measures were unfavorable functional outcome (3-month modified Rankin Scale 2-6); recurrent ischemic stroke; myocardial infarction or other arterial noncerebrovascular event; and death from any cause. RESULTS: Compared with those with at least 1 well-documented risk factor, the 127 (12.8%) patients without risk factors were younger (median age, 37 versus 44 years; P<0.001), likely to be females (54.3% versus 34.9%; P<0.001), and they had more frequently a low-risk source of cardioembolism (21.3% versus 8.1%; P<0.001), internal carotid artery dissection (12.6% versus 6.4%; P=0.011), or vertebral artery dissection (17.3% versus 7.2%; P<0.001). The groups had similar 3-month functional outcomes. Patients without well-documented risk factors had less frequently recurrent ischemic strokes (4.7% versus 13.6%; log rank P=0.014), noncerebrovascular arterial events (0% versus 6.1%; P=0.008), and lower long-term mortality (3.4% versus 14.3%; P=0.003) than did those with at least 1 risk factor. Adjusted for demographics and stroke etiology, the number of well documented risk factors was associated with higher risk for noncerebrovascular events. Increasing count of less well-documented risk factors was, in turn, independently associated with higher long-term mortality. CONCLUSIONS: In young adults with first-ever ischemic stroke, risk factor counts added independent prognostic information regarding noncerebrovascular events and mortality. PMID- 22052509 TI - Stroke prevention in the developing world. AB - In the early 21st century, developing countries are experiencing an ever increasing burden of stroke due its high morbidity and associated disability. Given the limited health resources available in developing countries, stroke prevention there is of paramount importance. This narrative review summarizes currently available evidence for stroke prevention in the developing world and outlines their major strategies and priorities. PMID- 22052510 TI - Stroke and stroke care in China: huge burden, significant workload, and a national priority. AB - At the same time as the world recognizes the rapid economic development in China, Chinese healthcare system has also had significant improvement. However, this nation of 1.4 billion faces tough challenges in treating stroke, the leading cause of death in China. The recently completed Chinese National Stroke Registry has provided new information on the status of stroke epidemiology, diagnosis, management, and prevention strategies in China. In this article, we summarized these new findings, described the effort of providing and improving stroke care, and illustrated the challenges in risk factor modification and secondary stroke prevention. Well-designed epidemiological surveys and clinical trials for stroke prevention and management are still urgently needed in China. PMID- 22052511 TI - Exaggerated postural blood pressure rise is related to a favorable outcome in patients with acute ischemic stroke. AB - BACKGROUND AND PURPOSE: The effects of early upright positioning in the acute phase of ischemic stroke on both blood pressure and functional outcome have not been previously examined. METHODS: Prospective investigation of mean arterial pressure, heart rate, and peripheral oxygen saturation in the supine, sitting, and (if achievable) active standing position 1, 2, and 3 days after an acute stroke was performed. Also investigated was the presence of a significant postural blood pressure rise and fall using orthostatic definitions and the relation to functional outcome after 3 months. RESULTS: One hundred sixty-seven patients were included (mean age, 68.5+/-15.2 years; median National Institutes of Health Stroke Scale, 7). Approximately 60% of the patients were able to stand. On average the mean arterial pressure increased when patients moved from the supine to sitting (Day 1: Delta 3.9 mm Hg; P<0.001) and from sitting to an active standing position (Day 1: Delta 4.6 mm Hg; P<0.001). Changes were most pronounced within the first 24 hours after a stroke. Blood pressure decreased significantly (fall) on standing in 13% of patients and increased significantly (rise) in 20% of the patients. The latter was independently associated with a favorable outcome (P=0.003). Moving to the standing position was accompanied by an increase of heart rate. No difference in oxygen saturation was observed in the various positions over the period of investigation. CONCLUSIONS: We found that a significant blood pressure rise during early upright positioning in patients with acute stroke was independently associated with a favorable outcome. No contraindication to early mobilization was found in this study. PMID- 22052512 TI - Neuroprotective effect of acute ethanol administration in a rat with transient cerebral ischemia. AB - BACKGROUND AND PURPOSE: Ethanol consumption is inversely associated with the risk of ischemic stroke, suggesting a neuroprotective effect. In a rat model of transient cerebral ischemia, we identified ethanol as a possible treatment for acute ischemic stroke. METHODS: Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Five sets of experiments were conducted: to determine the dose-response effect of ethanol on brain infarction and functional outcome; to determine whether combining ethanol and hypothermia produces synergistic neuroprotection; to determine the therapeutic windows of opportunity for ethanol in stroke; to test whether ethanol promotes intracerebral hemorrhage in a hemorrhagic or ischemic stroke or after administration of thrombolytics; and to test the affect of ethanol on hypoxia-inducible factor 1alpha protein expression. RESULTS: Ethanol at 1.5 g/kg reduced infarct volume and behavioral dysfunction when administered at 2, 3, or 4 hours after middle cerebral artery occlusion. The protective effect of ethanol was not improved when paired with hypothermia. Ethanol did not promote cerebral hemorrhage in hemorrhagic or ischemic stroke in combination with recombinant tissue-type plasminogen activator or urokinase. Ethanol treatment (1.5 g/kg) increased protein levels of hypoxia-inducible factor-1alpha at 3 hours postreperfusion. CONCLUSIONS: Ethanol exerts a strong neuroprotective effect when administered up to 4 hours after ischemia, increases expression of hypoxia-inducible factor 1alpha, and does not promote intracerebral hemorrhage when used with thrombolytics. Ethanol is a potential neuroprotectant for acute ischemic stroke. PMID- 22052513 TI - Ninety-day outcome rates of a prospective cohort of consecutive patients with mild ischemic stroke. AB - BACKGROUND AND PURPOSE: Prior studies have shown that patients with mild ischemic stroke have substantial disability rates at hospital discharge. We sought to determine disability rates at 90 days among patients not treated with thrombolytic therapy and explore the role of early neurological worsening. METHODS: We reviewed a prospective cohort of 136 consecutive patients with mild deficits (National Institutes of Health Stroke Scale score <= 5) presenting within 24 hours of onset and no baseline disability. Baseline MRIs were performed on all subjects. Five-day MRIs were performed on a prespecified subcohort. RESULTS: Among 136 patients, 40 (29%; 95% CI, 22%-38%) had poor outcomes (modified Rankin Scale score 2-6) at 90 days. Early worsening (4-point National Institutes of Health Stroke Scale increase; 25% versus 1%, P<0.001) and acute infarct growth (>10% on MRI-diffusion-weighted imaging; 79% versus 53%, P=0.02) from baseline to 5 days were more common among those with poor outcome. CONCLUSIONS: Patients with mild ischemic stroke have substantial rates (29%) of disability at 90 days. PMID- 22052514 TI - Resumption of oral anticoagulation after warfarin-associated intracerebral hemorrhage: yes. PMID- 22052515 TI - Resumption of oral anticoagulation after warfarin-associated intracerebral hemorrhage: no. PMID- 22052516 TI - A rat model of studying tissue-type plasminogen activator thrombolysis in ischemic stroke with diabetes. AB - BACKGROUND AND PURPOSE: Poststroke hyperglycemia and diabetes mellitus are associated with lower thrombolytic efficacy and an increased risk of postischemic cerebral hemorrhage. We aimed to develop a rodent model of thrombolysis in diabetic stroke that mimics the clinical situation. Method- Male 6-week Type I diabetic rats (14 weeks old) were subjected to embolic focal stroke and treated with tissue-type plasminogen activator at 1.5 hours. Reperfusion and 24-hour neurological outcomes were measured and compared with nondiabetic control rats. RESULTS: Diabetic rats exhibited resistance to thrombolytic reperfusion, larger infarction volumes, and increased intracerebral hemorrhage. CONCLUSIONS: This animal model would be relevant to future studies investigating pathophysiological mechanisms and in developing new therapeutic approaches to enhance the efficacy of tissue-type plasminogen activator thrombolysis in stroke patients with diabetes or poststroke hyperglycemia. PMID- 22052517 TI - Stroke and long-term exposure to outdoor air pollution from nitrogen dioxide: a cohort study. AB - BACKGROUND AND PURPOSE: Years of exposure to tobacco smoke substantially increase the risk for stroke. Whether long-term exposure to outdoor air pollution can lead to stroke is not yet established. We examined the association between long-term exposure to traffic-related air pollution and incident and fatal stroke in a prospective cohort study. METHODS: We followed 57,053 participants of the Danish Diet, Cancer and Health cohort in the Hospital Discharge Register for the first ever hospital admission for stroke (incident stroke) between baseline (1993-1997) and 2006 and defined fatal strokes as death within 30 days of admission. We associated the estimated mean levels of nitrogen dioxide at residential addresses since 1971 to incident and fatal stroke by Cox regression analyses and examined the effects by stroke subtypes: ischemic, hemorrhagic, and nonspecified stroke. RESULTS: Over a mean follow-up of 9.8 years of 52,215 eligible subjects, there were 1984 (3.8%) first-ever (incident) hospital admissions for stroke of whom 142 (7.2%) died within 30 days. We detected borderline significant associations between mean nitrogen dioxide levels at residence since 1971 and incident stroke (hazard ratio, 1.05; 95% CI, 0.99-1.11, per interquartile range increase) and stroke hospitalization followed by death within 30 days (1.22; 1.00-1.50). The associations were strongest for nonspecified and ischemic strokes, whereas no association was detected with hemorrhagic stroke. CONCLUSIONS: Long-term exposure to traffic-related air pollution may contribute to the development of ischemic but not hemorrhagic stroke, especially severe ischemic strokes leading to death within 30 days. PMID- 22052518 TI - Time course of vascular reactivity using repeated phase-contrast MR angiography in patients with carotid artery stenosis. AB - BACKGROUND AND PURPOSE: Cerebral vascular reactivity assessment is typically performed with 2 perfusion measurements before and after a vasodilatory challenge. The aim of this study was to assess the time course of the vasodilatory effect in the brain-feeding arteries after a challenge with acetazolamide in patients with a stenosis of the internal carotid artery (ICA). METHODS: Twenty-one patients with a symptomatic ICA stenosis and 18 healthy control subjects underwent 2-dimensional phase-contrast MR angiography to repeatedly measure the blood flow (mL/min) in both ICAs at baseline and in 5 minute intervals for 30 minutes after intravenous administration of acetazolamide. RESULTS: At baseline, the blood flow was significantly lower in the stenosed ICAs of patients (155 +/- 17 mL/min) than in the contralateral ICAs (237 +/- 21 mL/min, P<0.05) and the ICAs of healthy control subjects (249 +/- 15 mL/min, P<0.05) and remained lower throughout the time course. The maximum vasodilatory effect in the stenosed ICAs was observed after 15.3 +/- 0.9 minutes, which was significantly later than in the contralateral ICAs (within 12.9 +/- 0.7 minutes, P<0.05) and healthy ICAs (within 12.8 +/- 0.8 minutes, P<0.05). CONCLUSIONS: The onset of the maximum vasodilatory effect after administration of acetazolamide is delayed in patients with a symptomatic ICA stenosis. PMID- 22052519 TI - Translational research: from observational studies to health policy: how a cohort study can help improve outcomes after stroke. PMID- 22052520 TI - Renin-Angiotensin system modulators modestly reduce vascular risk in persons with prior stroke. AB - BACKGROUND AND PURPOSE: Although the efficacy of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in reducing future vascular events for patients with coronary heart disease is established, less is known about the precise benefit of these agents among patients with stroke. We evaluated whether use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers reduces future vascular events in persons with prior stroke. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials, and bibliographies of relevant trials and recent review articles to identify randomized controlled trials. Relative risk with 95% CI was used as a measure of the association between use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and risks of major vascular event (nonfatal stroke, nonfatal myocardial infarction, or death from cardiovascular causes) or stroke (ischemic or hemorrhagic) after pooling data across trials. RESULTS: Eight randomized controlled trials with 29 667 participants were identified. Use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers in persons with prior stroke was associated with lower risks of future major vascular events (relative risk, 0.91; 95% CI, 0.87-0.97; P=0.001; number needed to treat=71) and recurrent stroke (relative risk, 0.93; 95% CI, 0.86-0.99; P=0.03; number needed to treat=143). Heterogeneity was found among studies for end points of major vascular events (P=0.02, I(2)=61%) but not recurrent stroke (P=0.38, I(2)=6%). In subgroup analyses, there was generally no obvious heterogeneity among different study characteristics. CONCLUSIONS: Treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker has a clear but rather modest effect on reducing vascular risk in persons with prior stroke. PMID- 22052521 TI - Stroke epidemiology, patterns of management, and outcomes in Fortaleza, Brazil: a hospital-based multicenter prospective study. AB - BACKGROUND AND PURPOSE: Little information exists on the epidemiology and patterns of treatment of patients admitted to Brazilian hospitals with stroke. Our objective was to describe the frequency of risk factors, patterns of management, and outcome of patients admitted with stroke in Fortaleza, the fifth largest city in Brazil. METHODS: Data were prospectively collected from consecutive patients admitted to 19 hospitals in Fortaleza with a diagnosis of stroke or transient ischemic attack from June 2009 to October 2010. RESULTS: We evaluated 2407 consecutive patients (mean age, 67.7+/-14.4 years; 51.8% females). Ischemic stroke was the most frequent subtype (72.9%) followed by intraparenchymal hemorrhage (15.2%), subarachnoid hemorrhage (6.0%), transient ischemic attack (3%), and undetermined stroke (2.9%). The median time from symptoms onset to hospital admission was 12.9 (3.8-32.5) hours. Hypertension was the most common risk factor. Only 1.1% of the patients with ischemic stroke received thrombolysis. The median time from hospital admission to neuroimaging was 3.4 (1.2-26.5) hours. In-hospital mortality was 20.9% and the frequency of modified Rankin Scale score<=2 at discharge was less than 30%. Older age, prestroke disability, and having a depressed level of consciousness at admission were independent predictors of poor outcome; conversely, male gender was a predictor of good outcome. CONCLUSIONS: The prevalence of stroke risk factors and clinical presentation in our cohort were similar to previous series. Treatment with thrombolysis and functional independency after a stroke admission were infrequent. We also found long delays in hospital admission and in evaluation with neuroimaging and high in-hospital mortality. PMID- 22052522 TI - The X-chromosome has a different pattern of gene expression in women compared with men with ischemic stroke. AB - BACKGROUND AND PURPOSE: Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke. METHODS: RNA levels of 683 X-chromosome genes were measured on Affymetrix U133 Plus2.0 microarrays. Blood samples from patients with ischemic stroke were obtained at <= 3 hours, 5 hours, and 24 hours (n=61; 183 samples) after onset and compared with control subjects without symptomatic vascular diseases (n=109). Sex difference in X-chromosome gene expression was determined using analysis of covariance (false discovery rate <= 0.05, fold change >= 1.2). RESULTS: At <= 3, 5, and 24 hours after stroke, there were 37, 140, and 61 X-chromosome genes, respectively, that changed in women; and 23, 18, and 31 X-chromosome genes that changed in men. Female-specific genes were associated with post-translational modification, small-molecule biochemistry, and cell-cell signaling. Male-specific genes were associated with cellular movement, development, cell-trafficking, and cell death. Altered sex specific X-chromosome gene expression occurred in 2 genes known to be associated with human stroke, including galactosidase A and IDS, mutations of which result in Fabry disease and Hunter syndrome, respectively. CONCLUSIONS: There are differences in X-chromosome gene expression between men and women with ischemic stroke. Future studies are needed to decipher whether these differences are associated with sexually dimorphic immune response, repair or other mechanisms after stroke, or whether some of them represent risk determinants. PMID- 22052523 TI - Effects of public education by television on knowledge of early stroke symptoms among a Japanese population aged 40 to 74 years: a controlled study. AB - BACKGROUND AND PURPOSE: An educational campaign by mass media has been associated with great increases in the knowledge about early symptoms of stroke. However, few studies were conducted with a controlled community intervention study. METHODS: To clarify the effects of a 1-year television campaign for the whole population on improvement of knowledge about stroke symptoms in 2 cities, a campaign area and a control area in Japan were selected. Before and after the campaign, 1960 randomly selected residents aged 40 to 74 years answered a telephone survey regarding knowledge of early stroke symptoms. We calculated the percentage and 95% CIs of participants who correctly chose all 5 early symptoms of stroke in each area and in each year. RESULTS: Before the campaign, 53% of participants (95% CI, 50%-55%) in the campaign area and 46% (95% CI, 44%-49%) in the control area correctly chose 5 early symptoms. After the 1-year television campaign, knowledge was significantly improved only in the campaign area (campaign area, 63%; 95% CI, 60%-66%; control area, 51%; 95% CI, 48%-54%). After sex stratification, only women showed improved knowledge of early symptoms. The audience rate for the campaign television programs was found to be higher in women than in men. CONCLUSIONS: A 1-year stroke educational television campaign effectively improved knowledge about early stroke symptoms among Japanese women aged 40 to 74 years. No impact was found among men in this age group. Future studies should examine the impact of this approach on stroke knowledge among younger individuals and whether there are any behavioral changes that contribute to earlier presentation for treatment. PMID- 22052524 TI - Atherosclerosis: the XXIst century epidemic: a meeting at the Vatican. PMID- 22052525 TI - The dilemma of resuming anticoagulation after intracranial hemorrhage: little evidence facing big fears. PMID- 22052526 TI - Does adjunctive chemotherapy reduce remission rates compared to cortisone alone in unifocal or multifocal histiocytosis of bone? AB - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder that can affect almost any organ, including bone. Treatment options include local corticosteroid infiltration in isolated bone lesions and oral corticosteroids and chemotherapy in multifocal bone lesions. Several studies show local corticosteroid injection in unifocal bone lesions heal in more than 75% of patients with minimal side effects. Therefore, it is unclear whether chemotherapy adds materially to the healing rate. QUESTIONS/PURPOSES: We therefore compared overall survival, remission rate, and recurrence rate in patients with bone LCH treated with chemotherapy and corticosteroids or corticosteroids alone. METHODS: We retrospectively reviewed the records of 198 patients with LCH since 1950. Median age at diagnosis was 5 years, male-to-female ratio was 1.33, and the most frequent symptom was local pain (95%). We recorded the disease presentation, demographics, treatment, and clinical evolution of each patient. Minimum followup was 4 months (median, 24 months; range, 4-360 months). RESULTS: The survival rate of the systemic disease group was 76.5% (65 of 85) while the survival rate in the unifocal and multifocal bone involvement groups was 100% at a median 5-year followup. All patients with unifocal bone involvement and 40 of 43 (93%) with multifocal bone involvement had complete remission. One of 30 patients with multifocal bone involvement treated with chemotherapy and oral corticosteroids did not achieve remission whereas two of six receiving only corticosteroids did not achieve remission. CONCLUSIONS: Our observations suggest intralesional corticosteroid injection without adjunctive chemotherapy achieves remission in unifocal bone LCH but may not do so in multifocal single-system bone involvement. Larger series would be required to confirm this observation. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22052527 TI - Enantiopure metal-organic framework thin films: oriented SURMOF growth and enantioselective adsorption. PMID- 22052528 TI - Relative survival multistate Markov model. AB - Prognostic studies often have to deal with two important challenges: (i) separating effects of predictions on different 'competing' events and (ii) uncertainty about cause of death. Multistate Markov models permit multivariable analyses of competing risks of, for example, mortality versus disease recurrence. On the other hand, relative survival methods help estimate disease-specific mortality risks even in the absence of data on causes of death. In this paper, we propose a new Markov relative survival (MRS) model that attempts to combine these two methodologies. Our MRS model extends the existing multistate Markov piecewise constant intensities model to relative survival modeling. The intensity of transitions leading to death in the MRS model is modeled as the sum of an estimable excess hazard of mortality from the disease of interest and an 'offset' defined as the expected hazard of all-cause 'natural' mortality obtained from relevant life-tables. We evaluate the new MRS model through simulations, with a design based on registry-based prognostic studies of colon cancer. Simulation results show almost unbiased estimates of prognostic factor effects for the MRS model. We also applied the new MRS model to reassess the role of prognostic factors for mortality in a study of colorectal cancer. The MRS model considerably reduces the bias observed with the conventional Markov model that does not permit accounting for unknown causes of death, especially if the 'true' effects of a prognostic factor on the two types of mortality differ substantially. PMID- 22052529 TI - VP-1 quasispecies in human infection with polyomavirus BK. AB - Polyomavirus BK is a recognized cause of nephropathy and hemorrhagic cystitis in kidney or allogeneic hematopoietic stem cell transplant recipients. This study explored a role of genetic variations in capsid protein VP-1 gene as a factor in viral pathogenesis. VP-1 was amplified from 7 healthy subjects with viruria, 7 transplant patients with viruria, and 11 patients with viremia or nephropathy. PCR products were cloned and a total of 558 clonal sequences were subjected to phylogenetic analysis using standard methods. VP-1 quasispecies were found in 25/25 and coinfection with different genotypes in 12/25 subjects. Genotype II was found as an unexpected minority species in 5/25 individuals. Recombinant strains of uncertain biologic significance, which frequently contained genotype II and IV sequences were identified in 9/25 subjects. Viremia/nephropathy group was characterized by (a) greater sequence complexity in whole VP-1 versus BC loop and BC loop compared to the HI loop, (b) greater intra-strain genetic diversity in the BC loop compared to whole VP-1 protein and HI loop, (c) more non-synonymous substitutions (dN) in the BC loop compared to whole VP-1 and HI loop, (e) fewer synonymous substitutions (dS) compared to healthy-viruria group, and (f) selection pressure (dN/dS >1.0) exerted on VP-1. In conclusion, this study documents frequent occurrence of quasispecies in a host DNA polymerase dependent virus, which is theoretically expected to show high replication fidelity. Quasispecies occur even in healthy subjects with viruria, but evolutionary selection pressure directed at the viral capsid protein (VP-1) is seen only in patients with viremia or nephropathy. PMID- 22052530 TI - Evaluation and management of pediatric obstructive sleep apnea beyond tonsillectomy and adenoidectomy. AB - PURPOSE OF REVIEW: There is an increasing percentage of children with persistent obstructive sleep apnea (OSA) after removal of the tonsils and adenoids (T&A). Although sleep apnea has been an active area of research and treatment in the adult population, our awareness of this problem in children is still in its initial stages. In addition, therapies to successfully treat this residual OSA are still not fully established. It is important to develop evaluation and management protocols for these children. RECENT FINDINGS: This review will discuss risk factors associated with persistent OSA after T&A and techniques to evaluate the pediatric airway in order to identify the site, or sites, of obstruction. Various medical and surgical options are presented. SUMMARY: Clinicians need to be aware of the potential for persistent sleep disordered breathing and OSA in children, despite previous T&A. Evaluation protocols and techniques will differ in children, due to limitations in their cooperation during the physical examination. Alternative methods, such as airway endoscopy and cine MRI, are presented. Medical and surgical options are presented. Outcomes data for pediatric populations are rare. Multilevel, single stage surgery has a higher risk for oropharyngeal stenosis in children compared with adults and conservative, multistage approaches may be more appropriate. PMID- 22052531 TI - Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease. AB - Circulating microRNAs (miRNAs) are emerging as useful non-invasive markers of disease. The objective of this study was to use a mouse model of prostate cancer as a tool to discover serum miRNAs that could be assessed in a clinical setting. Global miRNA profiling identified 46 miRNAs at significantly altered levels (p <= 0.05) in the serum of TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice with advanced prostate cancer compared to healthy controls. A subset of these miRNAs with known human homologues were validated in an independent cohort of mice and then measured in serum from men with metastatic castration-resistant prostate cancer (mCRPC; n = 25) or healthy men (n = 25). Four miRNAs altered in mice, mmu-miR-141, mmu-miR-298, mmu-miR-346 and mmu-miR-375, were also found to be at differential levels in the serum of men with mCRPC. Three of these (hsa-miR 141, hsa-miR-298 and hsa-miR-375) were upregulated in prostate tumors compared with normal prostate tissue, suggesting that they are released into the blood as disease progresses. Moreover, the intra-tumoral expression of hsa-miR-141 and hsa miR-375 were predictors of biochemical relapse after surgery. This study is the first to demonstrate that specific serum miRNAs are common between human prostate cancer and a mouse model of the disease, highlighting the potential of such models for the discovery of novel biomarkers. PMID- 22052532 TI - FRAX underestimates fracture risk in patients with diabetes. AB - The study objective was to determine whether diabetes is a risk factor for incident hip or major osteoporotic fractures independent of the WHO fracture risk assessment tool (FRAX). Men and women with diabetes (n = 3518) and nondiabetics (n = 36,085) aged >=50 years at the time of bone mineral density (BMD) testing (1990 to 2007) were identified in a large clinical database from Manitoba, Canada. FRAX probabilities were calculated, and fracture outcomes to 2008 were established via linkage with a population-based data repository. Multivariable Cox proportional hazards models were used to determine if diabetes was associated with incident hip fractures or major osteoporotic fractures after controlling for FRAX risk factors. Mean 10-year probabilities of fracture were similar between groups for major fractures (diabetic 11.1 +/- 7.2 versus nondiabetic 10.9 +/- 7.3, p = 0.116) and hip fractures (diabetic 2.9 +/- 4.4 versus nondiabetic 2.8 +/ 4.4, p = 0.400). Diabetes was a significant predictor of subsequent major osteoporotic fracture (hazard ratio [HR] = 1.61, 95% confidence interval [CI] 1.42-1.83) after controlling for age, sex, medication use, and FRAX risk factors including BMD. Similar results were seen after adjusting for FRAX probability directly (HR = 1.59, 95% CI 1.40-1.79). Diabetes was also associated with significantly higher risk for hip fractures (p < 0.001). Higher mortality from diabetes attenuated but did not eliminate the excess fracture risk. FRAX underestimated observed major osteoporotic and hip fracture risk in diabetics (adjusted for competing mortality) but demonstrated good concordance with observed fractures for nondiabetics. We conclude that diabetes confers an increased risk of fracture that is independent of FRAX derived with BMD. This suggests that diabetes might be considered for inclusion in future iterations of FRAX. PMID- 22052533 TI - DC-biased AC-electrokinetics: a conductivity gradient driven fluid flow. AB - This paper studies the principles of fluid flow manipulation based on DC-biased AC-electrokinetics. This method makes use of planar parallel electrodes in a microfluidic channel in contact with an electrolyte solution, with a DC biased AC electrical signal applied to the electrode pair. Due to the application of DC bias, incipient Faradaic electrolytic reactions take place resulting in an increase of the ionic content of the bulk solution. The ionic content was found to be dissimilar at the cathodic and anodic sides of the channel and a conductivity difference of approximately 10% was measured for 2 V(DC). Fluid flow is generated by the action of the DC biased AC electric signal acting on the transverse conductivity gradient generated across the microchannel. The induced flow in the form of vortex was characterized experimentally and the results substantiated theoretically. The velocity of the induced flow vortex under the employed experimental conditions was ~600 to 700 MUm s(-1) which is faster than those obtained in conventional AC-electroosmosis and AC-electrothermal types of flows. PMID- 22052534 TI - Inhibition of encephalomyocarditis virus replication by shRNA targeting 1D and 3AB genes in vitro and in vivo. AB - Encephalomyocarditis virus (EMCV) could infect many host species and cause acute myocarditis and sudden death in pre-weaned piglets. It was necessary to develop new antiviral strategies for the treatment of the virus infection. Here, four plasmids expressing shRNA (small hairpin RNA) targeted to 1D or 3AB protein genes of EMCV were constructed and their inhibition efficiency on the replication of EMCV was evaluated in both BHK21 cells and mice. The results showed that three out of those four shRNA constructs could significantly inhibit EMCV replication in BHK21 cells on the levels of viral RNA and protein. Moreover, it was found that the shRNAs could suppress significantly the load of EMCV in the brain tissue of the mice pretreated with the constructs for 6-24 h. The clinical signs and pathological lesions of the mice in the groups inoculated with the shRNA constructed were milder obviously, compared with those in pSUPER-mN3 and challenge control groups. The survival rates of mice inoculated with pSUPER-3AB 1, pSUPER-3AB-2, and pSUPER-1D-1 for 12 h was 100, 80, and 40%, respectively, while, in the control groups it was only 20%. It indicated that the vector-based shRNA targeting to 3AB and 1D genes might be a potential anti-EMCV strategy. PMID- 22052535 TI - Influence of microstructure and chemical composition of sputter deposited TiO2 thin films on in vitro bioactivity. AB - Functionalisation of biomedical implants via surface modifications for tailored tissue response is a growing field of research. Crystalline TiO(2) has been proven to be a bone bioactive, non-resorbable material. In contact with body fluids a hydroxyapaptite (HA) layer forms on its surface facilitating the bone contact. Thus, the path of improving biomedical implants via deposition of crystalline TiO(2) on the surface is interesting to follow. In this study we have evaluated the influence of microstructure and chemical composition of sputter deposited titanium oxide thin films on the in vitro bioactivity. We find that both substrate bias, topography and the flow ratio of the gases used during sputtering affect the HA layer formed on the films after immersion in simulated body fluid at 37 degrees C. A random distribution of anatase and rutile crystals, formed at negative substrate bias and low Ar to O(2) gas flow ratios, are shown to favor the growth of flat HA crystal structures whereas higher flow ratios and positive substrate bias induced growth of more spherical HA structures. These findings should provide valuable information when optimizing the bioactivity of titanium oxide coatings as well as for tailoring process parameters for sputtered based production of bioactive titanium oxide implant surfaces. PMID- 22052536 TI - Effect of chitosan multilayers encapsulation on controlled release performance of drug-loaded superparamagnetic alginate nanoparticles. AB - The near monodispersed ibuprofen-loaded superparamagnetic alginate (AL/IBU/Fe(3)O(4)) nanoparticles with particles size less than 200 nm were prepared via the facile heterogeneous coprecipitation of the superparamagnetic Fe(3)O(4) nanoparticles, sodium alginate (AL) and the model drug ibuprofen (IBU) from the aqueous dispersion. Then the chitosan multilayers were self-assembled onto the AL/IBU/Fe(3)O(4) nanoparticles to produce novel magnetic-targeted controlled release drug delivery system, with chitosan as the polycation (CS) and the carboxymethyl chitosan (CMCS) as the polyanion. The drug controlled releasing behaviors of the AL/IBU/Fe(3)O(4) nanoparticles and the CS multilayers encapsulated ibuprofen-loaded superparamagnetic alginate ((AL/IBU/Fe(3)O(4))@(CS CMCS)(3)) nanoparticles were compared in the different pH media. In media with the same pH value, the encapsulated vessels exhibited the slower releasing rate. PMID- 22052537 TI - An ecoregional context for forest management on National Wildlife Refuges of the Upper Midwest, USA. AB - To facilitate forest planning and management on National Wildlife Refuges, we synthesized multiple data sources to describe land ownership patterns, land cover, landscape pattern, and changes in forest composition for four ecoregions and their associated refuges of the Upper Midwest. We related observed patterns to ecological processes important for forest conservation and restoration, with specific attention to refuge patterns of importance for forest landbirds of conservation priority. The large amount of public land within the ecoregions (31 80%) suggests that opportunities exist for coarse and meso-scale approaches to conserving and restoring ecological processes affecting the refuges, particularly historical fire regimes. Forests dominate both ecoregions and refuges, but refuge forest patches are generally larger and more aggregated than in associated ecoregions. Broadleaf taxa have increased in dominance in the ecoregions and displaced fire-dependent taxa such as pine (Pinus spp.) and other coniferous species; these changes in forest composition have likely also affected refuge forests. Despite compositional changes, larger forest patches on refuges suggests that they may provide better habitat for area-sensitive forest landbirds of mature, compositionally diverse forests than surrounding lands if management continues to promote increased patch size. We reason that although fine-scale research and monitoring for species of conservation priority is important, broad scale (ecoregional) assessments provide crucial context for effective forest and wildlife management in protected areas. PMID- 22052538 TI - Palladium-catalyzed desulfitative C-H arylation of heteroarenes with sodium sulfinates. PMID- 22052539 TI - Determining the extent of lateral neck dissection necessary to establish regional disease control and avoid reoperation after previous total thyroidectomy and radioactive iodine for papillary thyroid cancer. AB - BACKGROUND: The purpose of this study was to evaluate patients who underwent lateral neck dissection for fine-needle aspiration (FNA)-confirmed disease after total thyroidectomy and radioactive iodine (RAI) to determine the appropriate extent of resection necessary to avoid reoperation. METHODS: This study was conducted with a retrospective review of medical charts of 100 consecutive patients. RESULTS: Seventy-seven percent of initial lateral neck dissection specimens and 64% of reoperative lateral neck dissection specimens had more than 1 nodal level of involvement. The sensitivity and negative predictive value of preoperative ultrasound to determine whether a specific nodal level was involved were: level 2: 54% and 66.2%; level 3: 47% and 49.4%; level 4: 60% and 55.4%; and level 5: 42% and 88.5%, respectively. CONCLUSION: Patients undergoing lateral neck dissection after previous total thyroidectomy and RAI tend to have multiple involved nodes within multiple neck levels. Preoperative ultrasound is not sensitive enough to account for all of these involved nodes, therefore, a compartmental lateral neck dissection is recommended to minimize the risk of persistence and reoperation. PMID- 22052540 TI - MicroRNA-34b functions as a potential tumor suppressor in endometrial serous adenocarcinoma. AB - Endometrial serous adenocarcinoma (ESC) is aggressive and carries a poor prognosis. p53 is frequently mutated in ESC. microRNAs (miRNAs) are a direct p53 target and have been implicated in cancer cell behavior. In this study, we compared miRNA expression levels in ESC with the levels in endometrial endometrioid adenocarcinoma (EEC) and normal endometria. Six miRNAs were identified as having aberrant down-regulation specific to ESC with miR-34b being most pronounced. miR-34b was found to have promoter hypermethylation, which when reversed, restored miR-34b expression in the cell lines treated with 5-aza-2' deoxycytidine (DAC). Ectopic expression of miR-34b in turn inhibited cell growth, migration and most notably invasion. Our findings suggest a relationship among p53 mutation, miR-34b promoter methylation and tumor cell behavior. These effects are likely mediated by the downstream target of miR-34b, the proto-oncogene mesenchymal-epithelial transition factor (MET), a known prognostic factor in endometrial carcinomas. The expression of MET was reduced following the restoration of miR-34b in cell lines. In summary, our data suggest that miR-34b plays a role in the molecular pathogenesis of endometrial cancer. PMID- 22052541 TI - Molecular characterization of a new begomovirus that infects Euphorbia heterophylla and Solanum lycopersicum in Venezuela. AB - We report the complete nucleotide sequence of a begomovirus isolate infecting Euphorbia heterophylla and tomato (Solanum lycopersicum) in central Venezuela. Based on the current taxonomic criteria for the genus Begomovirus, the isolate was shown to represent a novel species, tentatively named Euphorbia mosaic Venezuela virus (EuMVV). Its DNA-A is most closely related to those of Euphorbia infecting begomoviruses from the Caribbean and Central America. The DNA B component forms a phylogenetic cluster with Euphorbia and Sida-infecting begomoviruses from the squash leaf curl virus (SLCV) cluster. EuMVV is transmissible to S. lycopersicum and Capsicum annuum by biolistics of infectious cloned DNA-A and DNA-B components and induces characteristic leaf downward curling and yellowing in S. lycopersicum and and yellowing and leaf distortion in Capsicum annuum. PMID- 22052542 TI - Suicides in the Canton of Zurich (Switzerland). AB - QUESTIONS: The Swiss Health Observatory recently reported that the Canton of Zurich ranked fourth highest among the Swiss cantons in regard to suicide rates. The aim of this study was to identify sociodemographic risk factors (such as sex, age, marital status, religion and place of residence) in relation to suicide rates in the Canton of Zurich, and to explore suicide methods and co-morbidities from all suicides in this area between 1995 and 2007. METHOD: Data from Swiss statistics on causes of death were analysed using statistical modelling. RESULTS: Suicides were found to be more frequent among men than women, and suicide was more prevalent in older or single people than in younger or married people, respectively. Age groups over 70 had increasingly high suicide rates compared to lower age groups. Investigating geographical distribution, highest suicide risks were found in the cities and high-income municipalities. The chosen suicide methods differed among age and sex groups. Poisoning was more than twice as frequent among women, and more common with increasing age in both sexes. Usage of firearms was about ten times as frequent among men. For train suicides, the age group of 10 to 19 years predominated. In 36% of suicide cases, mental disorders were listed as co-morbidities; in 12% malignant tumours were reported. CONCLUSIONS: Relatively low rates of mental illness were reported in older suicide victims, despite a massively rising suicide rate with increase of age, indicating that undiagnosed depression could contribute to the high suicide rates in the elderly. Demographic changes in the coming years may result in larger numbers of suicides. PMID- 22052543 TI - Ruthenium-catalyzed regioselective deuteration of alcohols at the beta-carbon position with deuterium oxide. AB - A convenient method for regioselective H/D exchange between D(2)O and alcohols at the beta-carbon position using the catalytic system [(p cymene)RuCl(2)]/ethanolamine/KOH is described. This method is applicable for deuteration of both primary and secondary alcohols. The H/D exchange reactions proceed through an oxidation/modification/reduction reaction sequence. Alcohols are first temporarily oxidized to carbonyl compounds by the hydrogen transfer catalyst. The carbonyl compounds then undergo deuteration at the carbon adjacent to the carbonyl group by keto-enol tautomerization in the presence of D(2)O and a catalytic amount of base. The deuterated carbonyl compounds are then reduced to produce deuterated alcohols. In support of the reaction mechanism, a well-defined bimetallic ruthenium complex was isolated from the reaction of [{(p cymene)RuCl(2)}(2)] with ethanolamine. The activity of this complex is similar to that of [{(p-cymene)RuCl(2)}(2)]/ethanolamine. PMID- 22052544 TI - Sox9 is upstream of microRNA-140 in cartilage. AB - MicroRNA-140 (miR-140) is specifically expressed in developing cartilage tissues. We have previously reported that miR-140 plays an important role during palatal cartilage development by modulating platelet-derived growth factor receptor alpha (pdgfra) in zebrafish. However, the regulatory mechanism of miR-140 in cartilage is still unknown. Using developing zebrafish, sox9a mutant (sox9a-/-) and sox9b mutant (sox9b-/-) zebrafish and SOX9 small interfering RNA in human chondrocytes, T/C-28 cells, we found that miR-140 is regulated by the cartilage master transcription regulator Sox9 in zebrafish and mammalian cells. PMID- 22052545 TI - The effect of Ni(2+) and Cu(2+) on the photocatalytic degradation of dyes by the chitosan-TiO(2) complex. AB - The present research combines biosorption and photocatalysis in a functional TiO(2)-immobilized chitosan adsorbent (CTA). CTA can degrade organic pollutants and adsorb metal ions simultaneously. Target pollutants were dyes of cationic (rhodamine B, Rh.B) and anionic (methyl orange, MO) nature, with Ni(2+) and Cu(2+) selected as heavy metals. The presence of Ni(2+) or Cu(2+) improved the degradation ability of CTA for MO, but inhibited the degradation of Rh.B, with Cu(2+) exhibiting stronger effects than Ni(2+). There was no significant difference in CTA activity when the metal ions were pre-adsorbed or when they coexisted in the solution with the organic dyes. Protons in the reaction system affected the degradation performance in a similar way for Ni(2+) and Cu(2+) leading to a different effect on the degradation for MO and Rh.B. An X-ray photoelectron spectroscopy analysis of the binding energies of the metal ions on the surface in the presence of the cationic or anionic dyes explained the different behaviors. Since anionic and cationic dyes possess chromogenic groups of different charges, they adversely affect the production of OH* radicals when coexisting with Cu(2+) or Ni(2+). PMID- 22052546 TI - Susceptibility of a Vibrio alginolyticus rpoS mutant to environmental stresses and its expression of OMPs. AB - Vibrio alginolyticus, one of the most important opportunistic pathogens, can be detected in human being and marine animals. Like other bacteria, V. alginolyticus is able to adapt to a variety of stressful environmental changes. The alternate sigma factor RpoS, which is a regulator during stationary phase, plays an important role in surviving under these stressful situations in many bacteria. Sequence analysis reveals a 990 bp open reading frame which is predicted to encode a 330-amino-acid protein with 68% to 96% overall identity to other reported sequences. To study the function of rpoS, the rpoS gene of V. alginolyticus VIB283 was cloned and an rpoS mutant was constructed by homologous recombination. Comparison of the study result of the wild type and the mutant showed that the mutant was more sensitive to stress conditions such as high osmolarity, oxidative stress, heat shock, and long-term starvation and that the LD(50) of the mutant strain to the zebra fish was about 2.8 times as that of the control strain. In addition, the SDS-PAGE analysis indicated that the outer membrane proteins (OMPs) existed great differences. PMID- 22052547 TI - High proton conductivity of water channels in a highly ordered nanowire. AB - A proton-conductive material based on a crystalline assembly of trimesic acid and melamine (TMA?M, see picture) is reported. Because of the ordered structure of the assembly, the water-saturated proton conductivity for the TMA?M assembly is 5.5 S cm(-1) , which is the highest proton conductivity measured to date. This exceptionally high conductivity and low-cost fabrication of the material make applications feasible for fuel-cell devices. PMID- 22052551 TI - Clinical evaluation of multiplex real-time PCR panels for rapid detection of respiratory viral infections. AB - Respiratory viral infections are one of the leading causes of morbidity and mortality, particularly in children, the elderly and immunocompromised persons. Rapid identification of viral etiology is critical in ruling out non-viral infections, initiating antiviral treatment and limiting the spread of the infection. Multiplex assays of more than one viral gene target in a single tube have the advantage of rapid screening of a large number of potential viral pathogens in a short time. A multiplex real-time PCR assay was used in this study for detection of respiratory RNA and DNA viral infections in 728 specimens received from 585 adult and pediatric patients comprised of symptomatic and asymptomatic organ transplant recipients and non-recipients for diagnosis of respiratory illnesses and for routine clinical monitoring. Multiplex PCR was more sensitive than the multiplex immunofluoresence culture assay (R-mix) and also detected additional respiratory viruses that were not covered by the R-mix panel. The number of respiratory viruses detected in symptomatic patients was significantly higher than asymptomatic patients in both adult and pediatric patients. Herpesviral infections were the predominant cause of lower respiratory tract infection in the organ transplant recipients, whereas respiratory syncytial virus was the most common pathogen in non-transplant patients particularly children. Multiplex real-time PCR for detection of respiratory viruses has the potential for rapid identification of viral pathogens. In this era of emerging viral infections, addition of newer viral targets to the multiplex PCR panels will be beneficial in determining both patient management and public health epidemiology. PMID- 22052552 TI - Sorafenib as treatment for relapsed or refractory pediatric acute myelogenous leukemia. AB - The prognosis for children with acute myelogenous leukemia (AML) has improved with overall survival rates of up to 65% [Pui et al. J Clin Oncol 2011; 29: 551 565]. However, the cure rate for AML lags behind that of acute lymphoblastic leukemia. Advances in AML leukemogenesis are leading to refined risk stratification. FMS like tyrosine kinase 3 (FLT3) mutations are independently associated with a poor prognosis. Newer kinase inhibitors, including sorafenib, have shown promise in adult studies. We report three pediatric patients with relapsed AML who achieved a sustained remission with sorafenib. Further trials are necessary to understand the role of sorafenib in pediatric AML. PMID- 22052553 TI - Direct measurement of backflux between oxaloacetate and fumarate following pyruvate carboxylation. AB - Pyruvate carboxylation (PC) is thought to be the major anaplerotic reaction for the tricarboxylic acid cycle and is necessary for de novo synthesis of amino acid neurotransmitters. In the brain, the main enzyme involved is pyruvate carboxylase, which is predominantly located in astrocytes. Carboxylation leads to the formation of oxaloacetate, which condenses with acetyl coenzyme A to form citrate. However, oxaloacetate may also be converted to malate and fumarate before being regenerated. This pathway is termed the oxaloacetate-fumarate-flux or backflux. Carbon isotope-based methods for quantification of activity of PC lead to underestimation when backflux is not taken into account and critical errors have been made in the interpretation of results from metabolic studies. This study was conducted to establish the degree of backflux after PC in cerebellar and neocortical astrocytes. Astrocyte cultures from cerebellum or neocortex were incubated with either [3-(13) C] or [2-(13) C]glucose, and extracts were analyzed using mass spectrometry or nuclear magnetic resonance spectroscopy. Substantial PC compared with pyruvate dehydrogenase activity was observed, and extensive backflux was demonstrated in both types of astrocytes. The extent of backflux varied between the metabolites, reaffirming that metabolism is highly compartmentalized. By applying our calculations to published data, we demonstrate the existence of backflux in vivo in cat, rat, mouse, and human brain. Thus, backflux should be taken into account when calculating the magnitude of PC to allow for a more precise evaluation of cerebral metabolism. PMID- 22052554 TI - Role of CD73 and extracellular adenosine in disease : Presented by Maria P. Abbracchio. PMID- 22052555 TI - Development of a comprehensive set of P2 receptor pharmacological research compounds. AB - Pharmacological manipulation of P2X and P2Y receptors has been critical to the elucidation of the biological roles of these receptors within a multitude of physiological and pathological processes. Initial purinergic signalling research made use of compounds based on pyridoxal phosphate, suramin and nucleotide analogues; recently developed compounds are often derivatives of these early tools. Tocris Bioscience first entered the field of purinergic signalling reagents with the commercial release of the pyridoxal phosphate derivative, iso PPADS. During the past two decades, Tocris has assembled a collection of over 50 compounds for P2 receptor modulation, including research tools commercialised from both academic and industrial laboratories. Recently, a number of P2X subtype selective compounds have been generated by pharmaceutical company medicinal chemistry programmes, supplementing our range of P2Y-selective compounds. Here, we detail the current, commercially available agonists and antagonists of P2X(1,2/3,3,4,7) and P2Y(1,6,11,12) receptors; considered together, they form the foundations of a comprehensive P2 receptor pharmacological 'toolkit'. PMID- 22052556 TI - Prenatal expression of purinergic receptor P2X3 in human dorsal root ganglion. AB - The dorsal root ganglion (DRG) is consisted of neurons that relay multiple types of spinal sensory stimuli to the central nervous system. Several neuroactive molecules may be involved in sensory modulation especially pain processing at the DRG, including the purinergic receptor P2X3 and calcitonin-gene-related peptide (CGRP). P2X3 receptor has been considered a promising pharmaceutical target for the development of new pain medicine. Currently, litter is known about the expression of P2X3 in the human DRG. The present study characterized the localization of P2X3 in prenatal human DRG obtained from fetuses at 4-8 gestational months, by comparing to CGRP expression as well as binding pattern of isolectin-B4 (IB4), a marker of small DRG neurons presumably relevant to nociception. P2X3 immunoreactivity (IR) appeared in most neuron-like perikarya, with their numerical density reduced during the gestational period studied. P2X3 IR was co-labeled very commonly with IB4 binding and infrequently with CGRP IR and was not colocalized with IR for the gliocyte marker glutamine synthetase. Together, the data show an early and broad expression of P2X3 in prenatal human DRG neurons, pointing to a biological role of purinergic signaling during the development of spinal sensory system. PMID- 22052557 TI - Purinergic receptors expressed in human skeletal muscle fibres. AB - Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and age matched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy in immunolabelled transverse sections of muscle biopsies. The receptors P2Y(4), P2Y(11) and likely P2X(1) were present intracellularly or in the plasma membrane of muscle fibres and were thus selected for further detailed morphological analysis. P2X(1) receptors were expressed in intracellular vesicles and sarcolemma. P2Y(4) receptors were present in sarcolemma. P2Y(11) receptors were abundantly and diffusely expressed intracellularly and were more explicitly expressed in type I than in type II fibres, whereas P2X(1) and P2Y(4) showed no fibre-type specificity. Both diabetic patients and healthy controls showed similar distribution of receptors. The current study demonstrates that purinergic receptors are located intracellularly in human skeletal muscle fibres. The similar cellular localization of receptors in healthy and diabetic subjects suggests that diabetes is not associated with an altered distribution of purinergic receptors in skeletal muscle fibres. We speculate that the intracellular localization of purinergic receptors may reflect a role in regulation of muscle metabolism; further studies are nevertheless needed to determine the function of the purinergic system in skeletal muscle cells. PMID- 22052558 TI - Items for developing revised classification criteria in systemic sclerosis: Results of a consensus exercise. AB - OBJECTIVE: Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated. Our objective was to select a set of items potentially useful for the classification of SSc using consensus procedures, including the Delphi and nominal group techniques (NGT). METHODS: Items were identified through 2 independent consensus exercises performed by the Scleroderma Clinical Trials Consortium and the European League Against Rheumatism Scleroderma Trials and Research Group. The first-round items from both exercises were collated and redundancies were removed, leaving 168 items. A 3-round Delphi exercise was performed using a 1-9 scale (where 1 = completely inappropriate and 9 = completely appropriate) and a consensus meeting using NGT was conducted. During the last Delphi round, the items were ranked on a 1-10 scale. RESULTS: In round 1, 106 experts rated the 168 items. Those with a median score of <4 were removed, resulting in a list of 102 items. In round 2, the items were again rated for appropriateness and subjected to a consensus meeting using NGT by European and North American SSc experts (n = 16), resulting in 23 items. In round 3, SSc experts (n = 26) then individually scored each of the 23 items in a last Delphi round using an appropriateness score (1-9) and ranking their 10 most appropriate items for the classification of SSc. Presence of skin thickening, SSc-specific autoantibodies, abnormal nailfold capillary pattern, and Raynaud's phenomenon ranked highest in the final list that also included items indicating internal organ involvement. CONCLUSION: The Delphi exercise and NGT resulted in a set of 23 items for the classification of SSc that will be assessed for their discriminative properties in a prospective study. PMID- 22052559 TI - Human papillomavirus in oropharyngeal squamous cell carcinomas in Korea: use of G1 cycle markers as new prognosticators. AB - BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) exhibits distinct patterns worldwide, but its prevalence has not been extensively evaluated in Korea. The E7 oncogene-mediated carcinogenesis and its meaning are yet to be uncovered for oropharyngeal SCCs. METHODS: In a Korean oropharyngeal SCC cohort, epidemiological indicators, HPV, and G1 cell cycle marker expressions were correlated with survival. RESULTS: Among 93 surgically treated patients with oropharyngeal SCCs, 49.5% were HPV+, which were significantly younger, and predominantly nonsmoking. They demonstrated better survival than HPV- (94% vs 60%). Patients who were HPV+ with oropharyngeal SCCs expressed higher p16, cyclin-dependent kinase 4 (cdk4), and lower pRb. The p16 (hazard ratio [HR] 2.39), pRb (HR 2.13), and CCND1 (HR 2.09) correlated with survival. Notably, combined markers like p16/cdk4 ratio (HR 2.47) and cdk4+CCND1 sum (HR 2.65) were more significantly correlated. CONCLUSION: Incidence of HPV related oropharyngeal SCC in Korea is similar to U.S.-European data. HPV presence correlates with improved survival. Expression ratios of G1 markers may predict survival of oropharyngeal SCCs better than each marker alone. PMID- 22052560 TI - Crossing the borders between neurology and psychiatry in functional neurological disorders. PMID- 22052561 TI - A novel, extremely alkaliphilic and cold-active esterase from Antarctic desert soil. AB - A novel, cold-active and highly alkaliphilic esterase was isolated from an Antarctic desert soil metagenomic library by functional screening. The 1,044 bp gene sequence contained several conserved regions common to lipases/esterases, but lacked clear classification based on sequence analysis alone. Moderate (<40%) amino acid sequence similarity to known esterases was apparent (the closest neighbour being a hypothetical protein from Chitinophaga pinensis), despite phylogenetic distance to many of the lipolytic "families". The enzyme functionally demonstrated activity towards shorter chain p-nitrophenyl esters with the optimal activity recorded towards p-nitrophenyl propionate (C3). The enzyme possessed an apparent T(opt) at 20 degrees C and a pH optimum at pH 11. Esterases possessing such extreme alkaliphily are rare and so this enzyme represents an intriguing novel locus in protein sequence space. A metagenomic approach has been shown, in this case, to yield an enzyme with quite different sequential/structural properties to known lipases. It serves as an excellent candidate for analysis of the molecular mechanisms responsible for both cold and alkaline activity and novel structure-function relationships of esterase activity. PMID- 22052563 TI - Enhancement of muramyldipeptide (MDP) immunostimulatory activity by controlled multimerization on dendrimers. AB - Peptidoglycan is a widespread bacterial PAMP molecule and a powerful initiator of innate immune responses. It consists of repeating units of MDP, which as a monomer is only weakly immunostimulatory. Here, MDP-coupled dendrimers were prepared and investigated for stimulation of pig blood mononuclear cells. Compared to monomeric MDP, MDP-dendrimers induced a markedly enhanced production of IL-12 p40, IL-1beta and IL-6 and completely down-regulated surface expression of B7 and MHC class II. These results suggest a possible novel strategy based on controlled multimerization of minimal PAMP motifs on dendrimers for preparing molecularly defined immunostimulators with predictable bioactivities. PMID- 22052564 TI - Core/shell Fe3O4 @SiO2 nanoparticles modified with PAH as a vector for EGFP plasmid DNA delivery into HeLa cells. AB - Novel stable core/shell Fe(3)O(4)@SiO(2)/PAH nanoparticles are synthesized using 15 nm Fe(3)O(4) as the template that is modified with PAH. The resulting nanoparticles can absorb plasmid DNA to mediate gene transfer in cultured HeLa cells. An electrophoretic assay suggests that the Fe(3)O(4)@SiO(2)/PAH nanoparticles protect the plasmid DNA from serum and DNase I degradation. A cell viability assay shows that the Fe(3)O(4)@SiO(2)/PAH nanoparticles exhibit a low cytotoxicity toward endothelial cells. Qualitative analysis of transfection in HeLa cells by nanoparticles carrying a plasmid DNA encoding EGFP demonstrates a fairly high expression level, even in the presence of serum. Thus, Fe(3)O(4)@SiO(2)/PAH nanoparticles are biocompatible and suitable for nonviral delivery, and may find applications in cancer therapy. PMID- 22052565 TI - Nano/microstructural effect of hydroxyapatite nanocrystals on hepatocyte cell aggregation and adhesion. AB - Hepatocyte cell aggregation and adhesion to HAp nanocrystals covered with SU-8 polymer micropatterns by nano/microfabrication techniques is demonstrated. The surface roughness and wettability of the HAp nanocrystals are significantly different from those of the SU-8 polymer. QCM-D and microscopic observation clearly reveal that the cells realize the surface properties to form aggregation and preferentially adhere to the HAp nanocrystals at 2 h after seeding, indicating the importance of the microstructures as well as the interfacial phenomena at a nanometer scale. PMID- 22052566 TI - Micelles from amphiphilic block copolyphosphates for drug delivery. AB - Amphiphilic block copolyphosphates (PEP-b-PIPPs) are synthesized by two-step ROP of cyclic phosphate monomers with different pedant groups. They can spontaneously self-assemble into approximately spherical micelles ranging in size between 89 and 198 nm in water. A typical hydrophobic anti-cancer drug DOX is encapsulated into the micelles. The release rate of DOX slows down with increasing hydrophobic block length of PIPP. DOX-loaded micelles are investigated for the proliferation inhibition of Hela cells and the DOX dose required for 50% cellular growth inhibition is found to be 0.8 ug mL(-1). It is demonstrated that PEP-b-PIPP micelles can be used as a safe and promising drug delivery system. PMID- 22052568 TI - Active-specific immunotherapy of human cancers with the heat shock protein Gp96 revisited. AB - The passive administration of specific antibodies that selectively target tumors is a well-known strategy in cancer treatment. Active immunotherapy using peptide vaccines, in contrast, is expected to induce specific, cytolytic T cells in the patient, which react against tumor antigens and destroy malignant cells. Although several concepts exist, the identification and low immunogenicity of tumor specific peptides remain a serious problem. Heat shock proteins (HSPs), notably glycoprotein (Gp) 96, are of special interest, because they are able to take molecular peptide-fingerprints of the protein array characteristic for a particular cell. Association of Gp96 with peptides has been shown to be essential for crosspresentation and activation of T cells. Consequently, Gp96-peptide complexes extracted from cancer cells harbor the tumor-specific peptides and are immunogenic, thus offering a tool for active immunization against the tumor. Already, several immunotherapy studies of human cancers have been carried out, showing no severe adverse effects but unfortunately only limited improvement in the clinical outcome. Vitespen, a commercial HSP-peptide complex vaccine based on tumor-derived Gp96, seems to induce an improved overall survival for subsets of early stage melanoma and kidney cancer patients. The limited access to vaccine material derived from the autologous tumor requires the development of alternative protocols. Moreover, counteracting immunosuppressive mechanisms induced by the malignancy might further improve the efficacy of vaccinations. This review critically analyzes the current state of clinical immunotherapy with Gp96, with special attention to Vitespen. PMID- 22052569 TI - Mechanistic origin of ligand-controlled regioselectivity in Pd-catalyzed C-H activation/arylation of thiophenes. AB - The use of ligands to control regioselectivity in transition-metal-catalyzed C-H activation/functionalization is a highly desirable but challenging task. Recently, Itami et al. reported an important finding relating to Pd-catalyzed ligand-controlled alpha/beta-selective C-H arylation of thiophenes. Specifically, the use of the 2,2'-bipyridyl ligand resulted in alpha-arylation, whereas the use of the bulky fluorinated phosphine ligand P[OCH(CF(3))(2)](3) resulted in beta arylation. Understanding of this surprising ligand-controlled alpha/beta selectivity could provide important insights into the development of more efficient catalyst systems for selective C-H arylation, and so we carried out a detailed computational study on the problem with use of density functional theory methods. Three mechanistic possibilities--S(E)Ar and migration, metalation/deprotonation, and Heck-type arylation mechanisms--were examined. The results showed that the S(E)Ar and migration mechanism might not be plausible, because the key Wheland intermediates could not be obtained. On the other hand, our study indicated that the metalation/deprotonation and Heck-type arylation mechanisms were both involved in Itami's reactions. In the metalation/deprotonation pathway the alpha-selective product (C5-product) was preferred, whereas in the Heck-type arylation mechanism the beta-selective product (C4-product) was favored. The ligands played crucial roles in tuning the relative barriers of the two different pathways. In the 2,2'-bipyridyl-assisted system, the metalation/deprotonation pathway was energetically advantageous, leading to alpha-selectivity. In the P[OCH(CF(3))(2)](3)-assisted system, on the other hand, the Heck-type arylation mechanism was kinetically favored, leading to beta-selectivity. An interesting finding was that P[OCH(CF(3))(2)](3) could produce a C-H...O hydrogen bond in the catalyst system, which was crucial for stabilization of the Heck-type transition state. In comparison, this C-H...O hydrogen bond was absent with the other phosphine ligands [i.e., P(OMe)(3), PPh(3), PCy(3)] and these phosphine ligands therefore favored the metalation/deprotonation pathway leading to alpha-selectivity. Furthermore, in this study we have provided theoretical evidence showing that the Heck-type arylation reaction could proceed through an anti-beta-hydride elimination process. PMID- 22052571 TI - Parkinsonism: heterogeneity of a common neurological syndrome. AB - Parkinsonism refers to a neurological syndrome embracing bradykinesia, muscle rigidity, tremor at rest and impaired postural reflexes, and involving a broad differential diagnosis. Having ruled out secondary causes (most importantly drugs), distinguishing levodopa-responsive idiopathic parkinson's disease (PD) from chiefly treatment-resistant and hence atypical parkinsonism is essential. Recent clinico-pathological studies using data-driven approaches have refined the traditional classifications of parkinsonism by identifying a spectrum of subtypes with different prognoses. For example, progressive supranuclear palsy (PSP), characterised by early vertical gaze limitation and falls, probably has a milder variant with predominant parkinsonism (PSP-P) which may respond quite well to levodopa before converting to the classical disease, relabelled Richardson syndrome (PSP-RS). Analysis of PD subcategories has shown that tremor-dominant forms are probably less benign than was hitherto thought and that in mild cases dystonia should rather be considered. In addition, life expectancy in early onset PD may be shortened. Despite the clinical and pathological overlap of the various subtypes, appreciating the heterogeneity of parkinsonism also includes identifying non-motor features such as early autonomous or cognitive problems which are potentially amenable to pharmacological treatment. Not least, non-motor symptoms, along with postural instability, render the patient particularly vulnerable to side effects, and hence avoiding unnecessary treatment is equally important in the management of parkinsonian disorders. PMID- 22052570 TI - Phenotypic psychiatric characterization of children with Williams syndrome and response of those with ADHD to methylphenidate treatment. AB - Williams syndrome (WS) is associated with cognitive deficits, special behavioral phenotype, and high rates of psychiatric disorders. The aims of the present study were: (1) To compare the rates of psychiatric disorders and repetitive behaviors in children with WS to children with idiopathic developmental disability (DDs); (2) To longitudinally assess the change in psychiatric disorders during adolescence in WS; (3) To assess retrospectively the effectiveness and safety of methylphenidate (MPH) treatment in WS children with ADHD. The study consisted of a cohort of 38 children and adolescents (age 13.1 +/- 5.2 years) with WS and a sample of age-matched DDs (age 15.0 +/- 3.1 years). A current follow-up evaluation was conducted after 5.6 +/- 1.6 years for 25 subjects (65.8%) of the WS cohort. The rate of most psychiatric disorders was found similar in children with WS and DD controls. Specific phobia, especially from noises, obsessive compulsive symptoms (e.g., aggressive obsessions and repetitive questions), and stereotypic behaviors (e.g., glancing), were more common in WS than DDs. In a longitudinal follow-up of the WS children, we found a decrease in the rate of anxiety disorders. In addition, a clinically significant improvement was reported in 72.2% of WS children with ADHD following MPH treatment. Sadness/unhappiness was the most common side effect associated with MPH treatment in WS, occurring in 2/3 of treated individuals. The present study further elucidates the neuropsychiatric phenotype of WS. Our results also suggest that MPH treatment for ADHD in WS warrants future prospective controlled trials. PMID- 22052572 TI - Enantioselective synthesis of cis-1,2-disubstituted cyclopentanes and cyclohexanes by Suzuki-Miyaura cross-coupling and iridium-catalyzed asymmetric hydrogenation. AB - A series of 1,2-disubstituted cyclohexene derivatives was prepared through Suzuki Miyaura cross-coupling of 2-bromo-1-cyclohexenecarbaldehyde or 2-carbomethoxy-1 cyclohexen-1-yl triflate with arylboronates. These tetra-substituted cyclic alkenes were subjected to Ir-catalyzed asymmetric hydrogenation. In this way cis 1-methoxymethyl-2-arylcyclohexanes were obtained in high yield with excellent enantio- and diastereoselectivities (up to >99% ee, >99% cis) by using phosphinomethyloxazolines as ligands. Asymmetric hydrogenation of analogous cyclopentene derivatives, prepared by Suzuki-Miyaura cross-coupling, proved to be more difficult and proceeded with lower enantioselectivities of up to 88% ee. The synthetic potential of this cross-coupling/asymmetric-hydrogenation strategy was demonstrated by an enantioselective route to chiral hexahydrofluorenones. PMID- 22052573 TI - Spatial scan statistics with overdispersion. AB - The spatial scan statistic has been widely used in spatial disease surveillance and spatial cluster detection for more than a decade. However, overdispersion often presents in real-world data, causing not only violation of the Poisson assumption but also excessive type I errors or false alarms. In order to account for overdispersion, we extend the Poisson-based spatial scan test to a quasi Poisson-based test. The simulation shows that the proposed method can substantially reduce type I error probabilities in the presence of overdispersion. In a case study of infant mortality in Jiangxi, China, both tests detect a cluster; however, a secondary cluster is identified by only the Poisson based test. It is recommended that a cluster detected by the Poisson-based scan test should be interpreted with caution when it is not confirmed by the quasi Poisson-based test. PMID- 22052576 TI - Is serum S100B protein a biomarker for amitriptyline-induced cardiovascular toxic effects? AB - The aim of this study was to assess the role of serum S100B protein as a biomarker for cardiovascular effects in an anesthetized rat model of amitriptyline toxicity. Adult male Wistar rats (n = 28) were randomized into four groups. While the control group received normal saline, the experimental groups received different doses of amitriptyline (0.625 or 0.94 or 1.25 mg/kg/min) infusion. Mean arterial pressure (MAP), heart rate (HR), electrocardiogram parameters, and serum S100B protein levels were recorded during the experiment. Linear Pearson's correlation coefficient was used to examine the association between cardiovascular parameters and serum levels of S100B protein. In the experimental groups, amitriptyline caused a significant decrease in MAP and HR (P < 0.001), a prolongation in QRS duration and QT intervals (P < 0.01), but it did not change PR intervals significantly. At the end of the experiment of the second group, a significant correlation was found between HR and serum S100B protein levels (r = -0.963, P = 0.037). At the end of the experiment of the third and fourth groups, a significant correlation between MAP, HR, all ECG parameters, and serum S100B protein levels was found. Serum S100B protein levels correlate well with amitriptyline-induced cardiovascular toxicity and can be used as a biomarker for predicting cardiovascular toxic effects of amitriptyline. PMID- 22052577 TI - Genetic transformation of Colletotrichum truncatum associated with anthracnose disease of chili by random insertional mutagenesis. AB - An Agrobacterium tumefaciens -mediated transformation (ATMT) system was successfully developed for Colletotrichum truncatum, the causal agent of chili anthracnose. A. tumefaciens carrying a hygromycin phosphotransferase gene (hph) and a green fluorescent protein (gfp) gene was used to transform the conidiospores of two C. truncatum pathotypes F8-3B and BRIP26974. Optimum transformation efficiency was obtained when equal volumes of A. tumefaciens strain AGL1 carrying either pJF1 or pPK2 binary vector was used to transform C. truncatum conidiospores at 10(6) /ml and co-cultivated at 24 degrees C for three days. Southern blot analysis indicated that 87.5% of the transformants contained randomly inserted, single copies of the T-DNA. Infection and colonisation of chili fruit at the mature red stage with F8-3B-GFP and BRIP26974-GFP confirmed the maintenance of virulence within these transformed pathotypes. In situ studies of infection and colonisation of the susceptible genotype fruit using fluorescent microscopy and transformed isolates of C. truncatum expressing GFP revealed that the pathogen was able to colonise healthy fruit tissue intercellularly in an endophytic manner without producing secondary biotrophic infection structures. The developed transformation system will be used to study the function of pathogenicity genes in C. truncatum using both forward and reverse genetics approaches. PMID- 22052578 TI - Stepwise sequential redox potential modulation possible on a single platform. AB - Step by step: The cluster [3,3'-Co(1,2-C(2)B(9)H(11))(2)](-) is an excellent platform for making a stepwise tunable redox potential system by dehydroiodination. With the addition of up to eight iodine substituents (purple; see picture), there is a fall in the E(1/2)(Co(III)/Co(II)) value from -1.80 V to -0.68 V (vs. Fc(+)/Fc; Fc = ferrocene). A practical application of this tunability has been observed in the growth of polypyrrole. PMID- 22052579 TI - Early diagnosis of lung cancer: evaluation of a community-based social marketing intervention. AB - BACKGROUND: Poor U.K. lung cancer survival rates may, in part, be due to late diagnosis. OBJECTIVES: To evaluate the effectiveness of a mixed-method community based social marketing intervention on lung cancer diagnoses. METHODS: A public awareness campaign in conjunction with brief intervention training in general practices was piloted in six localities with a high lung cancer incidence. End points were self-reported awareness of lung cancer symptoms; intention to seek healthcare; chest x-ray referral rates in primary care; secular trends in the incidence of lung cancer and stage at diagnosis, compared before and after the intervention. RESULTS: 21% (128/600) (95% CI 18% to 25%) of the targeted population recalled something about the campaign. Compared with a responder in the control area, the odds of a responder in the intervention area saying that they would visit their general practitioner and request a chest x-ray for a cough was 1.97 times (95% CI 1.18 to 3.31, p=0.01). Primary care chest x-ray referral rates increased by 20% in the targeted practices in the year following the intervention compared with a 2% fall in the control practices. The difference was highly significant, with an incidence rate ratio of 1.22 (95% CI 1.12 to 1.33, p=0.001). There was a 27% increase in lung cancer diagnoses in the intervention area compared with a fall in the control area. The incidence rate ratio was 1.42 (95% CI 0.83 to 2.44 p=0.199). CONCLUSION: This is encouraging early evidence that an awareness and early recognition initiative may facilitate lung cancer diagnosis. PMID- 22052580 TI - A novel solution-stamping process for preparation of a highly conductive aluminum thin film. AB - A novel solution-stamping process for the preparation of a highly conductive aluminum thin film on both rigid and flexible substrates is proposed. The superior electrical properties of Al thin films fabricated by the solution stamping process compared to silver and gold films fabricated from colloidal nanoparticles are experimentally demonstrated, and their applications in electronic circuits on rigid and flexible substrates and to organic light emitting diodes (OLEDs) are investigated. PMID- 22052581 TI - Heat treatment of Na2O-CaO-P2O5-SiO2 bioactive glasses: densification processes and postsintering bioactivity. AB - Because of their excellent bioactivity, bioactive glasses are increasingly diffused to produce biomedical devices for bone prostheses, to face the dysfunctions that may be caused by traumatic events, diseases, or even natural aging. However, several processing routes, such as the production of scaffolds or the deposition of coatings, include a thermal treatment to apply or sinter the glass. The exposure to high temperature may induce a devetrification phenomenon, altering the properties and, in particular, the bioactivity of the glass. The present contribution offers an overview of the thermal behavior and properties of two glasses belonging to the Na2O-CaO-P2O5-SiO2 system, to be compared to the standard 45S5 Bioglass((r)). The basic goal is to understand the effect of both the original composition and the thermal treatment on the performance of the sintered glasses. The new glasses, the one (BG_Na) with a high content of Na2O, the other (BG_Ca) with a high content of CaO, were fully characterized and sintering tests were performed to define the most interesting firing cycles. The sintered samples, treated at 880 degrees C and 800 degrees C respectively, were investigated from a microstructural point of view and their mechanical properties were compared to those of the bulk (not sintered) glass counterparts. The effect of sintering was especially striking on the BG_Ca material, whose Vickers hardness increased from 598.9 +/- 46.7 HV to 1053.4 +/- 35.0 HV. The in vitro tests confirmed the ability of the glasses, both in bulk and sintered form, of generating a hydroxyapatite surface layer when immersed in a simulated body fluid. More accurate biological tests performed on the sintered glasses proved the high bioactivity of the CaO-rich composition even after a heat treatment. PMID- 22052582 TI - Novel polymerase chain reaction method for detecting cutaneous human papillomavirus DNA. AB - There is no simple test to identify the human papillomavirus (HPV) genotypes that cause cutaneous warts. A new polymerase chain reaction (PCR) method, called SK PCR, was developed for this purpose. This PCR amplifies 210-238 base pairs of L1 DNA of 17 HPV types (HPV-1a, -2a, -3, -4, -7, -10, -27, -28, -29, -40, -57, -60, 63, -65, -77, -91, and -94), which are thought to cause various cutaneous warts, including common, flat, butcher's, punctate, and pigmented warts. The method is novel because the location of these primers is completely different from that of any previous PCR method for HPV. The target sequences are specific to alpha-, gamma-, and mu-papillomaviruses (PVs), but not to beta-PVs. Furthermore, direct sequencing and restriction fragment length polymorphism (RFLP) were used to determine the HPV genotypes. Fifty of samples of plantar warts were examined, and HPV-27 was identified in 22 warts, HPV-57 in 15 warts, and HPV-2a in 9 warts. These PVs, which are alpha species 4, were the most common. HPV-4 and -65 (gamma PVs) and HPV-1a and -63 (mu-PVs) were detected in one case each. A single HPV type was identified in all of these warts. This method appears to be useful for genotyping the HPVs causing skin warts, and for distinguishing between HPV induced warts and warty lesions unrelated to HPV infection. PMID- 22052583 TI - Multimodality treatment for sinonasal neuroendocrine carcinoma. AB - BACKGROUND: Neuroendocrine carcinoma (NEC) of the paranasal sinuses is rare, accounting for 5% of sinonasal malignancies. The purpose of this study was to assess prognostic factors and survival rates for sinonasal NEC. METHODS: A retrospective review of patients with NEC treated from 1990 to 2004 was performed. Patient demographics, TNM classification, treatment modality, recurrences, and survival were evaluated. RESULTS: NEC was identified in 28 patients; the most common primary site was the ethmoid sinuses. Most patients presented with advanced tumors; few had regional or distant metastasis. Local recurrence rate was 21%. Five-year overall survival (OS) and disease-specific survival (DSS) rates were 65% and 78%, respectively. Response to chemotherapy predicted for improved survival, although no differences in outcomes were noted between definitive management strategies. CONCLUSION: NEC of the paranasal sinuses is an exceedingly rare malignancy of the paranasal sinuses. Our data suggests definitive management with surgery or radiotherapy offers durable control. The response to chemotherapy may predict for overall outcomes. PMID- 22052584 TI - Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol. AB - OBJECTIVE: To compare the characteristics of female versus male gout patients and assess urate-lowering efficacy and safety of febuxostat or allopurinol treatment in women with gout. METHODS: This was a retrospective analysis of 4,101 hyperuricemic (serum urate [sUA] level >=8.0 mg/dl) gout subjects enrolled in 3 phase III comparative trials and randomized to receive placebo, febuxostat (40 mg, 80 mg, 120 mg, or 240 mg daily), or allopurinol (100 mg, 200 mg, or 300 mg daily, based on renal function). Baseline demographics and characteristics were summarized and compared between female and male subjects. Urate-lowering efficacy, which was defined as the proportion of subjects with sUA levels <6.0 mg/dl at final visit, was assessed for all subjects and, among women, according to baseline renal function. RESULTS: Female gout subjects (n = 226) were older with significantly higher rates of obesity and metabolic and cardiovascular comorbidities than their male counterparts. The percentage of female subjects with sUA levels <6.0 mg/dl at final visit was 0% in the placebo group, 54.3%, 85.1%, 81.0%, and 100.0% in the febuxostat 40 mg, 80 mg, 120 mg, and 240 mg groups, respectively, and 45.9% in the allopurinol group. Similar patterns of urate-lowering efficacy rates were observed when stratified by renal function. Among all the female subjects, febuxostat 80 mg was significantly more efficacious than allopurinol (P < 0.001). Rates of adverse events (AEs) were low. The most frequently reported AEs were upper respiratory tract infections, musculoskeletal/connective tissue disorders, and diarrhea. CONCLUSION: These data suggest that febuxostat 80 mg may be more efficacious than commonly prescribed doses of allopurinol in female gout subjects with high rates of comorbidities. PMID- 22052585 TI - The 2010 ACR/EULAR classification criteria for rheumatoid arthritis in the Heinola inception cohort--diagnoses confirmed by long-term follow-up. AB - The aim of this study was to evaluate the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA) in a cohort with early arthritis and true diagnosis confirmed by long-term follow-up. The criteria were tested in the Heinola community-based inception cohort of 121 true RA patients, while the control group consisted of 95 patients with definite spondyloarthritis and swollen joint(s), recruited in the same time. The diagnoses were confirmed by long-term follow-up. The fulfillment of the four 2010 criteria was determined at baseline (arthritis duration less than 6 months). Ninety-five in one hundred twenty-one (79%) of all RA patients, 54/68 (79%) of nonerosive (at baseline) RA patients, and 4/95 (4%) of controls fulfilled the 2010 criteria of RA, with better specificity (96%) than the 1987 ACR criteria (86%) in the same material. At baseline erosions were found in 44% of all RA patients and in 15% of the controls; rheumatoid factor was positive in 87% of the RA patients, but in 1% of the controls. One hundred seven in one hundred twenty-one (88%) of all RA patients and 16/95 (17%) of the controls fulfilled the 2010 total score criteria or were erosive at onset. The 2010 ACR/EULAR criteria should be documented in all patients with arthritis. If the criteria are not fulfilled at baseline in a nonerosive patient, the true diagnose may still be RA due to seroconversion or diagnostic manifestations during the follow-up. Indications for early disease modifying antirheumatic drug treatment may be present in active arthritis also in cases not fulfilling the new criteria at baseline. PMID- 22052586 TI - Relapsing polychondritis associated with hepatitis C virus infection. AB - This article is aimed to review of relapsing polychondritis (RP) and its association to hepatitis C virus (HCV) infection. A case of RP associated with HCV infection in a 59-year-old male is reported. The English medical literature was reviewed for RP and its association with HCV infection. RP is a rare autoimmune and multisystem disorder of unknown etiology in which the cartilaginous and related tissues are the primary targets of inflammation. HCV infection is a more common systemic illness with known hepatic and extra-hepatic manifestations. Although RP is associated with other diseases in about 35% of cases, only one case of RP, HCV, and mixed cryoglobulinemia has been reported. We report a case of RP associated with HCV infection. Treatment with pegylated interferon and ribavirin resulted in sustained virologic response and remission of treatment-resistant RP with azathioprine. We report a case of RP and associated HCV infection. Although treatment of HCV infection resulted in remission of RP, it is unknown if there is a causal relationship between HCV infection and RP. PMID- 22052587 TI - A case series to describe the clinical characteristics of foot ulceration in patients with rheumatoid arthritis. AB - The aim of this study was to describe the clinical characteristics of foot ulceration in patients with rheumatoid arthritis (RA). Adults with RA and current foot ulceration but without diabetes were recruited. Clinical examination included assessment of RA disease activity, foot deformity, peripheral vascular disease, neuropathy and plantar pressures. Location, wound characteristics and time to healing were recorded for each ulcer. Participants completed the Health Assessment Questionnaire and Leeds Foot Impact Scale. Thirty-two cases with 52 current ulcers were recruited. Thirteen patients (41%) experienced more than one current ulcer: 5 (16%) had bilateral ulceration, 15 (47%) had previous ulceration at a current ulcer site. The majority (n = 33) of open ulcers were located over the dorsal aspect of the interphalangeal joints (n = 12), plantar aspect of the metatarsophalangeal joints (MTPJs) (n = 12) and medial aspect of first MTPJs (n = 9). In ulcerated limbs (n = 37), ankle brachial pressure index (ABPI) was <0.8 in 2 (5%); protective sensation was reduced in 25 (68%) and peak plantar pressures were >6 kg/cm(2) in 6 (16%). Mean ulcer size was 4.84 by 3.29 mm. Most ulcers (n = 42, 81%) were superficial; five (9.6%) were infected. Time to healing was available for 41 ulcers: mean duration was 28 weeks. Three ulcers remained open. In conclusion, foot ulceration in RA is recurrent and multiple ulcers are common. Whilst ulcers are small and shallow, time to achieve healing is slow, posing infection risk. Reduced protective sensation is common in affected patients. The prevalence of arterial disease is low but may be under estimated due to high intolerance of ABPI. PMID- 22052588 TI - [Shock therapy: Which catecholamine is the best?]. PMID- 22052589 TI - [Adult non-hodgkin lymphoma: Has high-dose chemotherapy improved the prognosis?]. PMID- 22052590 TI - Assembling phthalocyanine dimers through a platinum(II) acetylide linker. AB - Phthalocyanine (Pc) dimers connected through trans-platinum(II) diacetylide linkers have been prepared by reaction of the corresponding ethynylphthalocyanines with trans-bis(triethylphosphine)platinum(II) chloride. Special emphasis was placed on the analysis of the ground- and excited-state features of these compounds in relation to butadiyne-bridged Pc dimers and the corresponding monomers. Both Zn(II)-containing Pc dimers exhibit long-lived triplet excited states. The insertion of sigma-bonded trans-platinum(II) diacetylide spacers decoupled the two Pc groups and led to an appreciable acceleration (by a factor of up to 10) of the radiative and nonradiative decay rate of the singlet and triplet excited states. PMID- 22052592 TI - Enantioselective Ir(I)-catalyzed carbocyclization of 1,6-enynes by the chiral counterion strategy. AB - Enantioenriched bicyclo[4.1.0]hept-2-enes were synthesized by Ir(I)-catalyzed carbocyclization of 1,6-enynes. No chiral ligands were used, CO and PPh(3) were the only ligands bound to iridium. Instead, the stereochemical information was localized on the counterion of the catalyst, generated in situ by reaction of Vaska's complex (trans-[IrCl(CO)(PPh(3))(2)]) with a chiral silver phosphate. Enantiomeric excesses up to 93% were obtained when this catalytic mixture was used. (31)P NMR and IR spectroscopy suggest that formation of the trans- [Ir(CO)(PPh(3))(2)](+) moiety occurs by chlorine abstraction. Moreover, density functional theory calculations support a 6-endo-dig cyclization promoted by this cationic moiety. The chiral phosphate anion (O-P*) controls the enantioselectivity through formation of a loose ion pair with the metal center and establishes a C-H...O-P* hydrogen bond with the substrate. This is a rare example of asymmetric counterion-directed transition-metal catalysis and represents the first application of such a strategy to a C-C bond-forming reaction. PMID- 22052591 TI - Metastatic cutaneous squamous cell carcinoma shows frequent deletion in the protein tyrosine phosphatase receptor Type D gene. AB - Cutaneous squamous cell carcinoma (cSCC) is the second most common form of nonmelanoma skin cancer (NMSC), and its incidence is increasing rapidly. Metastatic cSCC accounts for the majority of deaths associated with NMSC, but the genetic basis for cSCC progression remains poorly understood. A previous study identified small deletions (typically <1 Mb) in the protein tyrosine phosphatase receptor Type D (PTPRD) gene that segregated with more aggressive cSCC. To investigate the apparent association between deletion within PTPRD and cSCC metastasis, a series of 74 formalin-fixed paraffin-embedded tumors from 31 patients was analyzed using a custom Illumina 384 SNP microarray. Deletions were found in 37% of patients with metastatic cSCC and were strongly associated with metastatic tumors when compared to those that had not metastasized (p = 0.007). Subsequent mutation analysis revealed a higher mutation rate for PTPRD than has been reported in any other cancer type, with 37% of tumors harboring a somatic mutation. Conversely, bisulfite sequencing showed that methylation was not a mechanism of PTPRD disruption in cSCC. This is the first report to observe an association between deletion within PTPRD and metastatic disease and highlights the potential use of these deletions as a diagnostic biomarker for tumor progression. Combined with the high mutation rate observed in our study, PTPRD is one of the most commonly altered genes in cSCC and warrants further investigation to determine its significance for metastasis in other tumor types. PMID- 22052593 TI - Synthesis and in vitro characterization of semitelechelic poly[N-(2 hydroxypropyl)methacrylamide]-trastuzumab conjugates targeted to breast cancer. AB - Trastuzumab (TRZ) is a humanized monoclonal antibody that targets the extracellular domain of the human epidermal growth factor receptor type 2 (Her2). Semitelechelic (ST) poly[N-(2-hydroxypropyl)methacrylamide]-TRZ conjugates are successfully synthesized and evaluated as a potential drug delivery system that actively targets Her2-overexpressing cancer cells. The ST backbone shows favorable characteristics when conjugated to TRZ. The conjugate exhibits comparable and prolonged anticancer activity when compared to free TRZ in Her2 overexpressing breast cancer cell lines. PMID- 22052594 TI - GRIK4/KA1 protein expression in human brain and correlation with bipolar disorder risk variant status. AB - The kainate class of ionotropic glutamate receptors is involved in the regulation of neuronal transmission and synaptic plasticity. Previously we reported that a deletion variant within the gene GRIK4, which encodes the KA1 kainate receptor subunit, was associated with a reduced risk of bipolar disorder and increased GRIK4 mRNA abundance. Using a high resolution immunohistochemistry technique, we characterized KA1 protein localization in human brain and performed a genotype protein expression correlation study. KA1 was expressed in specific populations of neuronal cells in the cerebellum and all layers of the frontal and parahippocampal cortices. In the hippocampus, strong KA1 expression was observed in the stratum pyramidale and stratum lucidum of CA3 and CA2, in cell processes in CA1, in the neuropil of the CA4 region, in polymorphic cells including mossy fiber neurons in the hilus, and dentate gyrus (DG) granule cells. Mean counts of KA1 positive DG granule cells, hippocampal CA3 pyramidal cells, and layer 1 of the frontal cortex were significantly increased in subjects with the deletion allele (P = 0.0005, 0.018, and 0.0058, respectively) compared to subjects homozygous for the insertion. Neuronal expression levels in all regions quantified were higher in the deletion group. These results support our hypothesis that the deletion allele affords protection against bipolar disorder through increased KA1 protein abundance in neuronal cells. Biological mechanisms which may contribute to this protective effect include KA1 involvement in adult hippocampal neurogenesis, HPA axis activation, or plasticity processes affecting neuronal circuitry. PMID- 22052595 TI - Click chemistry finds its way into covalent porous organic materials. PMID- 22052596 TI - A spatially and temporally explicit model for determining the exposure of juvenile salmon to agricultural pesticides in freshwater. AB - In this paper, we present a novel approach for determining the probable co occurrence of juvenile salmon or steelhead with agricultural pesticides and apply it to spring Chinook (Oncorhynchus tshawytscha) salmon in the Willamette Basin, Oregon. We adapted a published exposure analysis framework by explicitly considering fish migration among habitat units and assuming that habitat use is proportional to habitat quality. Temporal variability in habitat use was accounted for via biweekly time steps over the entire period when a single brood was expected to spawn until the last juvenile migrated to sea. Spatial variability was accounted for at the watershed and reach scale. Exposure to 6 acetylcholinesterase-inhibiting insecticides at any life stage was expressed in terms of the future adults (adult-equivalents; AEQ). Several datasets were available to inform our framework with input values on extent of spring Chinook fish use, habitat quality preferred by juvenile spring Chinook, choice of juvenile life-history pathways, timing of emergence, and timing of migration either in-stream or to sea. We used insecticide concentration profiles constructed from available monitoring data to demonstrate the effect of accounting for variation in space and time on predicted exposure to chemical residues. In contrast to the assumption commonly used in screening-level risk assessments that the entire population in a watershed is exposed, available data applied to our model framework indicate that a small fraction of AEQ juveniles in the Willamette Basin would co-occur with detectable concentrations of the 6 insecticides. Overall, our results indicated that the use of a spatially and temporally explicit framework yields a better understanding of the proportion of organisms potentially impacted by agricultural pesticides. PMID- 22052597 TI - Association between polymorphisms of the cytokine and cytokine receptor genes and immune response to hepatitis B vaccination in a Chinese Han population. AB - The immune response to hepatitis B vaccination varies among individuals. It has been reported that polymorphisms in cytokine and cytokine receptor genes are associated with these individual differences. The aim of the current study was to investigate the association between polymorphisms of the Th1/Th2 cytokine and cytokine receptor genes and the response to hepatitis B vaccination in a Chinese Han population. A total of 10 single nucleotide polymorphisms distributed in 6 genes (TNFRSF1A, IL12A, IL12B, IFNG, IL4, and IL10) were genotyped in 214 high responders [hepatitis B surface antibody (anti-HBs) >=1,000 mIU/ml] and 107 low responders (anti-HBs: 10-99 mIU/ml). The minor CTCTAA allele of rs17860508 in the IL12B gene was associated with a low response to hepatitis B vaccination (P = 0.039, odds ratio = 1.41, 95% confidence interval = 1.00-1.99). In addition, a significant gene-gene interaction was found: the frequency of the combined genotypes IL12A rs2243115 TT and IL12B rs17860508 CTCTAA/CTCTAA was significantly higher in the low-response group than in the high-response group (P = 0.008, odds ratio = 2.19, 95% confidence interval = 1.23-3.93). These findings suggest that polymorphisms in the IL12A and IL12B genes might play an important role jointly in determining the response to hepatitis B vaccination. PMID- 22052598 TI - Purification and characterization of a xylanase from Bacillus subtilis isolated from the degumming line. AB - Xylanases catalyze the hydrolysis of xylan, a major hemicellulose component of cell wall besides cellulose in most plant species. To extract cellulose fibers, it will be invaluable to screen for more effective xylanase-producing microorganisms. In this paper a new strategy for easy screening of xylanase producing strains from the degumming line was presented. Using this strategy, a weak-acidic, cellulase-free xylanase from Bacillus subtilis has been isolated, purified and characterized. The xylanase showed high specific activity (36,633.4 U/mg), presented stable characteristics and can be separated and purified simply, with molecular weight 23.3 kD, pI 9.63. It reached its optimal activity at pH 5.8 and 60 degrees C, and retained over 80% of its maximal activity after pre incubation at temperature 60 degrees C or pH 4.6 ~ 6.4. Also, a two-step purification procedure based on the combination of ultrafiltration and gel filtration chromatography was introduced and described, achieving 17-fold purification with 68.11% yield. PMID- 22052600 TI - Effects of malachite green on the mRNA expression of detoxification-related genes in Nile tilapia (Oreochromis niloticus) and other major Chinese freshwater fishes. AB - The use of malachite green (MG) in fish farming is prohibited in China due to its potentially toxicological and carcinogenic nature, but it is still illegally used in some places. The aim of this study was to investigate the time and concentration-dependent responses of xenobiotic metabolizing and detoxification related genes in diverse fishes exposed to MG both in vivo and in vitro. Experimental fish were administered to two exposure groups of malachite green (MG) (0.10 and 0.50 mg L-1) for 8 h. The hepatocytes isolated from Nile tilapia were incubated with MG (0.5, 1.0, and 2.0 mg L-1) for 8 and 24 h, respectively. In vivo, exposure to 0.10 and 0.50 mg L-1 MG for 8 h caused significant changes of the detoxification-related genes on the mRNA expression levels. Low concentration (0.10 mg L-1) level of MG induced significant increase on the mRNA expression level of GSTR gene in Nile tilapia and other fishes. The mRNA expression of grass carp UCP2 was significantly induced when exposed to 0.5 mg L 1 MG. However, the mRNA expression levels of GSTA, CYP1A, and GPX were inhibited significantly by 0.5 mg L-1 MG in Nile tilapia, grass carp, and Taiwan snakehead. In vitro, the significant increase of mRNA expression of these genes was detected after exposure to 0.5 mg L-1 MG (UCP2), and 1.0 mg L-1 MG (CYP1A1, GSTA, GSTR, and UCP2). The induction of hepatic CYP1A1, GSTA, GSTR, and UCP2 in response to MG suggested a potential role of fish CYP1A1, GSTA, GSTR, and UCP2 in MG metabolism. PMID- 22052601 TI - Temporal stability of alexithymia in cancer patients following a psychological intervention. AB - OBJECTIVE: The state-trait nature of alexithymia is not fully resolved. The aim of this article was to evaluate the temporal stability of alexithymia in cancer patients after psychological intervention. DESIGN: Absolute and relative stability of alexithymia was evaluated in 104 cancer patients who received multicomponent psychological treatment or usual medical care. RESULTS: Alexithymia scores significantly decreased in treated patients and increased in the control group, thus showing that the lack of absolute stability (i.e., the change of personality scores over time) likely was because of the effect of the treatment versus the control condition. The relative stability (i.e., the extent to which the inter-individual differences remain the same over time) of alexithymia after 6 months was, however, demonstrated with multiple regressions, after controlling for anxiety, depression, and cancer-related pain. CONCLUSIONS: This study confirms the relative stability of alexithymia and that the lack of absolute stability of the construct is influenced by psychological intervention in cancer patients. PMID- 22052599 TI - Effectiveness of a clinical practice intervention in early rheumatoid arthritis. AB - OBJECTIVE: To compare the outcome of early rheumatoid arthritis (RA) patients in a country where early clinics were established versus the outcome of patients in nonprotocolized clinics. METHODS: We compared 2 multicenter cohorts: an RA cohort derived from an early arthritis registry set in 36 reference hospitals in which a specific intervention was established (Evaluation of a Model for Arthritis Care in Spain [SERAP]), and a historical control cohort of patients with early RA attending 34 rheumatology departments (Prognosis in Rheumatoid Arthritis [PROAR] cohort). Effectiveness was tested by comparing the change in the Disease Activity Score in 28 joints (DAS28), the change in the Health Assessment Questionnaire (HAQ), and the change in the Sharp/van der Heijde radiologic score using marginal structural models. RESULTS: A total of 161 early RA patients were recruited in the PROAR cohort and 447 in the SERAP cohort. Being a SERAP patient was inversely correlated with activity, resulting in a decrease of -0.24 (95% confidence interval [95% CI] -0.39, -0.08) units in the population average of the DAS28 after adjustment was made. Moreover, intervention may be seen as a protective factor of radiologic damage, with a decrease of -0.05 (95% CI -0.09, -0.01) units in the logarithm of the total Sharp/van der Heijde score. On the other hand, a decrease in functional impairment was detected, but intervention was not statistically associated with HAQ changes. CONCLUSION: Preventing major radiographic progression in a 2-year term inside structured and organized special programs for the management of disease, such as early arthritis clinics, are effective compared to nonprotocolized referrals, treatment, and followup. PMID- 22052602 TI - Self-assembly and embedding of nanoparticles by in situ reduced graphene for preparation of a 3D graphene/nanoparticle aerogel. AB - A 3D graphene architecture can be prepared via an in situ self-assembly of graphene prepared by a mild chemical reduction. Fe(3) O(4) nanoparticles are homogeneously dispersed into graphene oxide (GO) aqueous suspension and a 3D magnetic graphene/Fe(3) O(4) aerogel is prepared during the reduction of GO to graphene. This provides a general method to prepare 3D graphene/nanoparticle composites for a wide range of applications including catalysis and energy conversion. PMID- 22052603 TI - Effects of berberine on hippocampal neuronal damage and matrix metalloproteinase 9 activity following transient global cerebral ischemia. AB - Berberine, an isoquinoline alkaloid with a long history of use in Chinese medicine, has several important pharmacological effects. Several studies have revealed that berberine has neuroprotective and neuropsychiatric effects. However, there are few reports regarding the protective effect of berberine against neuronal damage following transient global cerebral ischemia. In this study, mice were subjected to 20 min of global brain ischemia and sacrificed 72 hr later. Berberine was administered for 7 days prior to ischemia and daily until sacrifice. Mice treated with berberine showed reduced matrix metalloproteinase-9 (MMP-9) activity. Berberine inhibited gelatinase activity directly in in situ zymography and reduced neuronal damage following global ischemia. Laminin expression and NeuN expression were markedly reduced in CA1 and CA2 areas after ischemia, and berberine reduced the laminin degradation and neuronal loss. In the TUNEL assay, damaged neurons were also apparent in the CA1 and CA2 areas, and berberine reduced TUNEL-positive cells. These data demonstrate that berberine, a plant alkaloid, may protect from hippocampal neuronal damage following transient global ischemia by reducing MMP-9 activity. PMID- 22052604 TI - RP1 and autosomal dominant rod-cone dystrophy: novel mutations, a review of published variants, and genotype-phenotype correlation. AB - Rod-cone dystrophies (retinitis pigmentosa [RP]) are a clinically and genetically heterogeneous group of inherited retinal disorders characterized by photoreceptor degeneration. RP1 is a major gene underlying autosomal dominant (ad) RP, though prevalence figures vary depending on the origin of the cases from 0-10% of all adRP. Some mutations in RP1 also lead to autosomal recessive (ar) RP. Herein, we review all previously reported and several novel RP1 mutations in relation to the associated phenotype in RP1 patients from a French adRP cohort. Prevalence studies from this cohort show that 5.3% of the cases have RP1 mutations. This is in accordance with other studies reported from United Kingdom and United States. The majority of mutations represent truncating mutations that are located in a hot spot region of the gene. Similarly, we identified in total four novel deletions and nonsense mutations, of which two may represent recurrent mutations in this population. In addition, a novel missense mutation of uncertain pathogenicity was identified. Including our findings to date, 47 RP1 mutations are known to cause adRP. Variable penetrance of the disease was observed in our and other cohorts. Most patients with RP1 mutations show classical signs of RP with relatively preserved central vision and visual field. PMID- 22052605 TI - Donor site morbidity of free ulnar forearm flap. AB - BACKGROUND: The purpose of this study was to evaluate the donor site morbidity of the free ulnar forearm flap (UFF). METHODS: Consecutive patients undergoing free UFF between 1982 and 2009 were retrospectively reviewed. In addition, detailed assessment of hand function and donor site cosmesis was performed in the most recent 50 patients followed up for at least 12 months. RESULTS: In all, 62 of the 242 free UFF donor sites (26%) were closed directly and the remainder required split thickness skin grafting. Donor site complications included total (n = 1) and partial (n = 17) skin graft loss and persistent hypertrophic scarring (n = 4). There was minimal incidence of cold intolerance, parasthesia, and pain; no reduction in joint mobility, grip and pinch strength, and sensory dysfunction, with excellent donor site cosmesis. CONCLUSIONS: UFF has several advantages, including the possibility of direct closure of the donor defect, and reduced morbidity and excellent donor site cosmesis. PMID- 22052606 TI - The role of fluoroquinolones in the management of urinary tract infections in areas with high rates of fluoroquinolone-resistant uropathogens. AB - Fluoroquinolones have been recommended as the drugs of choice for the empirical treatment of uncomplicated and complicated urinary tract infections (UTIs) caused by trimethoprim-sulfamethoxazole-resistant uropathogens. However, because of the increased use of both oral and parenteral fluoroquinolones for other kinds of infections, increasing rates of resistance to fluoroquinolones among the most common uropathogens have challenged this recommendation, particularly in the Asia Pacific region. The current interpretative criteria for the in vitro susceptibility of uropathogens to some fluoroquinolones, such as levofloxacin and ciprofloxacin, are set according to their therapeutic efficacy for bloodstream infections, and are not specific to UTIs. Fluoroquinolones exhibit concentration dependent antibacterial activity, high renal excretion, and relatively early and prolonged urinary bactericidal titers. Whether or not current interpretative criteria for the in vitro susceptibility of uropathogens to fluoroquinolones predict clinical failure in treating UTIs is still controversial. The Clinical and Laboratory Standards Institute (CLSI) has established UTI-specific breakpoints for resistance to a few fluoroquinolones. However, the application of high-dose fluoroquinolone therapy for the treatment of mild to moderate UTIs caused by isolates with higher minimum inhibitory concentrations (MICs) of several fluoroquinolones needs to be re-validated based on more relevant clinical studies, prudent pharmacokinetic/pharmacodynamic (PK/PD) considerations, and thorough study of the mutant prevention concentration of fluoroquinolones in the treatment of UTI. PMID- 22052607 TI - Serotype 3 is a common serotype causing invasive pneumococcal disease in children less than 5 years old, as identified by real-time PCR. AB - Serotype 3 is one of the most often detected pneumococcal serotypes in adults and it is associated with serious disease. In contrast, the isolation of serotype 3 by bacterial culture is unusual in children with invasive pneumococcal disease (IPD). The purpose of this study was to learn the serotype distribution of IPD, including culture-negative episodes, by using molecular methods in normal sterile samples. We studied all children<5 years of age with IPD admitted to two paediatric hospitals in Catalonia, Spain, from 2007 to 2009. A sequential real time polymerase chain reaction (PCR) approach was added to routine methods for the detection and serotyping of pneumococcal infection. Among 257 episodes (219 pneumonia, 27 meningitis, six bacteraemia and five others), 33.5% were identified by culture and the rest, 66.5%, were detected exclusively by real-time PCR. The most common serotypes detected by culture were serotypes 1 (26.7%) and 19A (25.6%), and by real-time PCR, serotypes 1 (19.8%) and 3 (18.1%). Theoretical coverage rates by the PCV7, PCV10 and PCV13 vaccines were 10.5, 52.3 and 87.2%, respectively, for those episodes identified by culture, compared to 5.3, 31.6 and 60.2% for those identified only by real-time PCR. Multiplex real-time PCR has been shown to be useful for surveillance studies of IPD. Serotype 3 is underdiagnosed by culture and is important in paediatric IPD. PMID- 22052608 TI - Divergent electrocardiographic responses to whole and particle-free diesel exhaust inhalation in spontaneously hypertensive rats. AB - Diesel exhaust (DE) is a major contributor to traffic-related fine particulate matter (PM)(2.5). Although inroads have been made in understanding the mechanisms of PM-related health effects, DE's complex mixture of PM, gases, and volatile organics makes it difficult to determine how the constituents contribute to DE's effects. We hypothesized that exposure to particle-filtered DE (fDE; gases alone) will elicit less cardiac effects than whole DE (wDE; particles plus gases). In addition, we hypothesized that spontaneously hypertensive (SH) rats will be more sensitive to the electrocardiographic effects of DE exposure than Wistar Kyoto rats (WKY; background strain with normal blood pressure). SH and WKY rats, implanted with telemeters to monitor electrocardiogram and heart rate (HR), were exposed once for 4 h to 150 MUg/m(3) or 500 MUg/m(3) of wDE (gases plus PM) or fDE (gases alone) DE, or filtered air. Exposure to fDE, but not wDE, caused immediate electrocardiographic alterations in cardiac repolarization (ST depression) and atrioventricular conduction block (PR prolongation) as well as bradycardia in SH rats. Exposure to wDE, but not fDE, caused postexposure ST depression and increased sensitivity to the pulmonary C fiber agonist capsaicin in SH rats. The only notable effect of DE exposure in WKY rats was a decrease in HR. Taken together, hypertension may predispose to the potential cardiac effects of DE and components of DE may have divergent effects with some eliciting immediate irritant effects (e.g., gases), whereas others (e.g., PM) trigger delayed effects potentially via separate mechanisms. PMID- 22052609 TI - Brain perfusion SPECT in patients with PHACES syndrome under propranolol treatment. AB - INTRODUCTION: Children with PHACES syndrome (PS) and visual impairment or stridor show a dramatic and immediate response to propranolol. However, this beta blocking drug could be responsible for an eventually increased risk of ischemic stroke due to the underlying cerebral vascular disease. To more accurately understand the effects of propranolol on brain vascularization, we examined PS patients treated with this drug for airway or visual complications using brain perfusion SPECT (Single Photon Emission Computed Tomography). In the past, this examination has been shown to be useful in the management of patients with different neurovascular disorders. METHODS: Clinical records and imaging studies were reviewed in 7 patients with a diagnosis of PS. All patients underwent magnetic resonance angiography (MRA), echocardiography, chest X-ray and ophthalmologic, neurological, and cardiologic assessments. They received 2-3 mg/kg/day propranolol in an attempt to treat stridor or avoid ophthalmologic occlusion. We performed SPECT after 3-6 months of treatment. RESULTS: SPECT showed a normal uptake in the frontal and temporal regions despite vascular abnormalities found with MRA imaging. Significant improvements of symptoms and in the volume of the hemangioma were noted in all cases without signs of a reduction of brain blood perfusion. CONCLUSIONS: Propranolol treatment was safe in our patients who did not show signs of perfusion changes. The high sensitivity for detecting functional impairment makes brain perfusion SPECT useful in the diagnosis and follow-up of patients with PS considered at risk of neurovascular impairment. Accurate knowledge of its pathophysiological basis, together with the appropriate technique and careful interpretation of reporting, will enhance the clinical use of brain SPECT in those patients. PMID- 22052610 TI - Sigma-1 receptor agonist fluvoxamine for delirium in older adults. PMID- 22052611 TI - Catenation of self-assembled nanorings. PMID- 22052612 TI - Optimization of calyculin A-induced premature chromosome condensation assay for chromosome aberration studies. AB - Calyculin A-induced premature chromosome condensation (PCC) assay is a simple and useful method to assess structural and numerical chromosome aberrations in cells. Our hypothesis in this study is that suboptimum calyculin A induction of PCC resulting in fuzzy compactness and/or shortened length chromosomes would decrease the detection sensitivity of numerical and structural chromosome aberrations such as small PCC rings and small excess fragments. In this study, an optimization of calyculin A exposure on chromosome morphology and PCC induction frequency was investigated using a human peripheral blood lymphocyte (PBL) ex vivo irradiation ((60) Co-gamma rays; ~0.6 Gy/min; 0-30 Gy) model. Treatment with calyculin A (50 nM) for 15 and 30 min resulted in 11.3 +/- 2.7 and 9.9 +/- 1.6-fold increases in the frequency of G(2) /M-PCC cells with extended length chromosomes compared with the 60-min treated group over a broad dose range (0 to 20 Gy), respectively. The G(2) /M-PCC scoring index per PCC in 15- and 30-min treated groups was increased by 1.9 +/- 0.2 (P = 0.001) and 1.8 +/- 0.2 (P = 0.001) compared with the 60-min treated group over 0-20 Gy, respectively. The G(2) /M-PCC efficiency of 30-min treated group was highest in the three conditions (i.e., 15-, 30-, and 60-min treatment) of calyculin A exposure. Calyculin A (50 nM) treatment for 30 min before the 48-h harvest of mitogen-stimulated human PBL is optimum for the formation of suitable chromosome morphology necessary to assess structural chromosome aberrations induced by exposure to radiation using the chemical induced-PCC assay. Published 2011 Wiley Periodicals, Inc. PMID- 22052613 TI - Synthesis of gold square-like plates from ultrathin gold square sheets: the evolution of structure phase and shape. PMID- 22052614 TI - Childhood onset of left ventricular dysfunction in a female manifesting carrier of muscular dystrophy. AB - Duchenne muscular dystrophy and Becker muscular dystrophy are X-linked disorders that result from a mutation in the dystrophin gene that reduces the production or effectiveness of the protein dystrophin. These disorders are clinically characterized by progressive muscle degeneration. Manifesting female carriers are generally not identified as such until after puberty, when symptoms such as muscle weakness may arise. This clinical report describes a female manifesting carrier who started to show deterioration of left ventricular systolic function, but no marked skeletal muscle weakness, at the age of 10 years. The patient's cardiac function improved significantly after dual drug therapy with an ACE inhibitor (enalapril) and a beta-blocker (carvedilol). Our case adds to the existing evidence that left ventricular myocardial dysfunction may occur during childhood in female carriers of dystrophinopathies. PMID- 22052616 TI - Age- and time-dependent changes in cancer incidence among immigrants to Sweden: colorectal, lung, breast and prostate cancers. AB - To examine the role of gender, age at immigration and length of stay on incidence trends of common cancers, we studied risk of colorectal, lung, breast and prostate cancers in immigrants to Sweden from 1958 to 2008. The nationwide Swedish Family-Cancer Database was used to calculate standardized incidence ratios for common cancers among immigrants compared to Swedes. Immigrants were classified into "high-risk" countries when their risk was increased, into "low risk" when their risk was decreased and into "other" when their risk was nonsignificant. Among those who immigrated at younger age (<30 years), we found an increasing trend for colorectal cancer risk in low-risk men and high-risk women. Among those who immigrated at older age (>= 30 years), a decreasing lung cancer risk in high-risk men and an increasing breast cancer risk in low-risk women were observed. The increasing trend of prostate cancer risk was independent of age at immigration. The risk trends for "other" immigrants were between the risks of low- and high-risk countries. The gender-specific shifts in cancer risks in immigrants toward the risk in natives indicate a major role of sex, age at immigration and environmental exposures in colorectal and lung cancers risks. In contrast, the unchanged trend of breast cancer among those who immigrated at younger ages and an increasing trend for those who migrated at older ages may suggest a limited effect for environmental exposures, especially at younger age. Our study points out a role of age at immigration on the risk trend of cancer. PMID- 22052615 TI - Design, synthesis and characterisation of guanosine-based amphiphiles. AB - A small library of sugar-modified guanosine derivatives has been prepared, starting from a common intermediate, fully protected on the nucleobase. Insertion of myristoyl chains and of diverse hydrophilic groups, such as an oligoethylene glycol, an amino acid or a disaccharide chain, connected through in vivo reversible ester linkages, or of a charged functional group provided different examples of amphiphilic guanosine analogues, named G1-G7 herein. All of the sugar modified derivatives were positive in the potassium picrate test, showing an ability to form G-tetrads. CD spectra demonstrated that, as dilute solutions in CHCl(3), distinctive G-quadruplex systems may be formed, with spatial organisations dependent upon the structural modifications. Two compounds, G1 and G2, proved to be good low-molecular-weight organogelators in polar organic solvents, such as methanol, ethanol and acetonitrile. Ion transportation experiments through phospholipid bilayers were carried out to evaluate their ability to mediate H(+) transportation, with G5 showing the highest activity within the investigated series. Moreover, G3 and G5 exhibited a significant cytotoxic profile against human MCF-7 cancer cells in in vitro bioassays. PMID- 22052617 TI - Fluorescent micelles based on star amphiphilic copolymer with a porphyrin core for bioimaging and drug delivery. AB - Star-shaped poly(epsilon-caprolactone)-b-poly(ethylene oxide) amphiphilic copolymer with a tetrakis-(4-aminophenyl)-terminated porphyrin core was synthesized. Paclitaxel (PTX)-loaded polymeric micelles were prepared by the self assembly of the star copolymer and in situ encapsulation of PTX. The fluorescent characteristic of the porphyrin moiety allowed the cellular uptake and biodistribution of the PTX-loaded micelles to be monitored by fluorescent imaging. The PTX-loaded micelles can be readily internalized by cancer cells and have a slightly higher cytotoxicity than clinic PTX injection Taxol. In vivo real time fluorescent imaging revealed that the micelles could accumulate at tumor site via the blood circulation in tumor-bearing mice. In vivo antitumor efficacy examinations indicated that the PTX-loaded micelles had significantly superior efficacy in impeding tumor growth than Taxol and low toxicity to the living mice. PMID- 22052618 TI - Surveillance of adenovirus D in patients with epidemic keratoconjunctivitis from Fukui Prefecture, Japan, 1995-2010. AB - Human adenoviruses species D (HAdV-D) are known to cause severe epidemic keratoconjunctivitis. However, the isolation rate of HAdV-D is not high, because HAdV-D is usually slow to propagate. Although new types of HAdV-D have been reported, accurate surveillance has not been performed because of difficulties in culturing the viruses and lack of a practical identification method. In this study, HAdV-Ds were detected and identified from patients with epidemic keratoconjunctivitis in the Fukui Prefecture during 1995-2010 by PCR, loop mediated isothermal amplification (LAMP) of DNA, and conventional virus isolation and neutralization tests. All samples were subjected to culture and PCR and LAMP. A total of 124 strains of HAdV-D were detected from 157 patients with epidemic keratoconjunctivitis. The strains consisted of the following types: D8 (n = 8), D19 (n = 4), D37 (n = 40), D53 (n = 5), D54 (n = 66), and D56 (n = 1). Among these, D53, D54, and D56 are new types that have been reported recently. The results of this study demonstrated that new types of HAdV-D caused epidemic keratoconjunctivitis during 1995-2010, and included an outbreak of keratoconjunctivitis caused by HAdV-D54. The LAMP method was able to detect and identify HAdV-D53 and HAdV-D54 in 1 hr, and may therefore be applicable for use at the bedside. PMID- 22052619 TI - Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia. AB - Temozolomide sensitivity is determined by methylation of the O(6)-methylguanine DNA methyltransferase (MGMT) promoter. This study assessed whether the temozolomide dose can be tailored by MGMT promoter status and whether protracted, low-dose temozolomide can "prime" blasts in patients with unmethylated MGMT (unMGMT). Elderly patients with high-risk AML were stratified by MGMT methylation. Patients with methylated MGMT (mMGMT) received temozolomide 200 mg/m(2) orally for 7 days every 4 weeks, while patients with unMGMT received temozolomide 100 mg/m(2) orally for 14 days followed by 200 mg/m(2) orally for 7 days every 6weeks. Of 36 patients (median age, 75 years), 31 (86%) had an unMGMT promoter. Overall response rate for the entire cohort was 36%. Patients with mMGMT and unMGMT had similar response rates (40% vs. 29%). Median duration of response and overall survival (OS) among responders were 29 and 35 weeks, respectively. Induction deaths (ID) occurred in 25% of patients, mostly caused by disease progression. Hematological toxicities were the most common adverse event. Toxicities were similar between patients on conventional versus protracted schedules. High HCT-CI scores were predictive of lower CR rate, higher ID, and shorter OS, while bone marrow blast count <50% at screening predicted for improved responses. Temozolomide, dosed according to MGMT methylation status, demonstrated modest clinical activity in elderly patients with AML, especially in those presenting with fewer comorbidities and low disease burden. The trial was registered on www.ClinicalTrials.gov as #NCT00611247. PMID- 22052620 TI - Cloning and characterization of a phosphate transporter gene in Dunaliella salina. AB - The full-length cDNA of a Na(+) -dependent Pi transport gene (DsSPT1) in Dunaliella salina was cloned by 3' and 5' Rapid Amplification of cDNA Ends (RACE), with an open reading frame (ORF) encoding 716 predicted amino acids, which exhibited 60.5% identity to that of Na(+) -dependent Pi transport 1 (DvSPT1) from Dunaliella viridis. Hydrophobicity and secondary structure prediction revealed 11 conserved transmembrane domains similar to those found in DvSPT1 from D. viridis and PHO89 from Saccharomyces cerevisiae. The result of real-time quantitative PCR showed that expression level of DsSPT1 was enhanced at first and reached its peak at 90 min after salt stress; however, D. salina cells rapidly absorbed extracellular inorganic phosphorus which was determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) during the first 5 min under salt stress. It suggested that D. salina on the absorption of inorganic phosphorus was regulated at DsSPTI posttranslational level. PMID- 22052621 TI - Intolerance of uncertainty, depression, and anxiety: the moderating and mediating roles of rumination. AB - OBJECTIVES: This study examined rumination as a moderator and mediator between intolerance of uncertainty (IU) and depression and anxiety symptoms. DESIGNS: The study was a cross sectional study. Survey data were collected from 332 undergraduate students at a large Midwestern university. RESULTS: The results from hierarchical analyses supported the moderator role of rumination. A high level of rumination enhanced the association between IU and depression symptoms. In addition, both high and low levels of rumination strengthened the relation between IU and anxiety symptoms. Results from structural equation modeling analyses indicated that rumination fully mediated the relation between IU and depression symptoms, but only partially mediated the association between IU and anxiety symptoms. CONCLUSIONS: The results supported rumination as a moderator and mediator in the association between IU and depression and anxiety symptoms. Future research and practical implications are discussed. PMID- 22052622 TI - Stage-dependent toxicity of bisphenol a on Rhinella arenarum (anura, bufonidae) embryos and larvae. AB - The acute and chronic toxicity of bisphenol A (BPA) was evaluated on the common South American toad Rhinella arenarum embryos and larvae by means of continuous and pulse exposure treatments. Embryos were treated continuously from early blastula (S.4) up to complete operculum (S.25), during early larval stages and by means of 24 h pulse exposures of BPA in concentrations ranging between 1.25 and 40 mg L(-1) , in order to evaluate the susceptibility to this compound in different developmental stages. For lethal effects, S.25 was the most sensitive and gastrula was the most resistant to BPA. The Teratogenic Index for neurula, the most sensitive embryonic stage for sublethal effects was 4.7. The main morphological alterations during early stages were: delayed or arrested development, reduced body size, persistent yolk plug, microcephaly, axial/tail flexures, edemas, blisters, waving fin, underdeveloped gills, mouth malformations, and cellular dissociation. BPA caused a remarkable narcotic effect from gill circulation stage (S.20) onwards in all the organisms exposed after 3 h of treatment with 10 mg L(-1) BPA. After recovering, the embryos exhibited scarce response to stimuli, erratic or circular swimming, and spasmodic contractions from 5 mg L(-1) onwards. Our results highlight the lethal and sublethal effectsof BPA on R. arenarum embryos and larvae, in the last case both at structural and functional levels. PMID- 22052623 TI - Role of FDG-PET as a biological marker for predicting the hypoxic status of tongue cancer. AB - BACKGROUND: To determine whether 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) could serve as a useful technique predicting tumor hypoxia and prognosis in tongue cancer, we assessed the relationship between FDG uptake and the levels of hypoxia-related markers. METHODS: Tumor uptake of FDG in 33 patients with T2 tongue cancer was assessed by measuring maximum standardized uptake values (SUVmax). Expression of hypoxia-inducible factor (HIF)-1alpha, carbonic anhydrase (CA)-9, glucose transporter (GLUT)-1, and erythropoietin receptor (EPOR), was determined by immunohistochemical staining. Correlation between SUVmax and the expression of hypoxia-related markers was assessed and multivariate analysis was performed to determine what parameters affected clinical outcomes. RESULTS: We observed strong correlations between SUVmax and expression of HIF-1alpha (p < .05), CA-9 (p < .01), and GLUT-1 (p < .01). SUVmax, HIF-1alpha expression, and tumor grade were significant independent predictors of disease-free survival (DFS). CONCLUSION: SUVmax may be a good noninvasive biomarker for prediction of hypoxic status and prognosis of patients with T2 tongue cancer. PMID- 22052624 TI - Systematic review of the epidemiology of systemic lupus erythematosus in the Asia Pacific region: prevalence, incidence, clinical features, and mortality. AB - OBJECTIVE: Systemic lupus erythematosus (SLE), a chronic multisystem autoimmune disease with a wide spectrum of manifestations, shows considerable variation across the globe, although there is little evidence to indicate its relative prevalence in Asia. This review describes its prevalence, severity, and outcome across countries in the Asia-Pacific region. METHODS: We conducted a systematic literature search using 3 groups of terms (SLE, epidemiology, and Asia-Pacific countries) of EMBase and PubMed databases and non-English language resources, including Chinese Wanfang, Korean KMbase, Korean College of Rheumatology, Japana Centra Revuo Medicina, Taiwan National Digital Library of Theses and Dissertations, and Taiwanese, Thai, and Vietnamese journals. RESULTS: The review showed considerable variation in SLE burden and survival rates across Asia Pacific countries. Overall crude incidence rates (per 100,000 per year) ranged from 0.9-3.1, while crude prevalence rates ranged from 4.3-45.3 (per 100,000). Higher rates of renal involvement, one of the main systems involved at death, were observed for Asians (21-65% at diagnosis and 40-82% over time) than for whites. While infections and active SLE were leading causes of death, a substantial proportion (6-40%) of deaths was due to cardiovascular involvement. The correlation between the Human Development Index and 5-year survival was 0.83. CONCLUSION: This review highlights the need to closely monitor Asian SLE patients in Asian countries for renal and cardiovascular involvement, especially those who may not receive proper treatment and are therefore at greater risk of severe disease. We hope this will encourage further research specific to this region and lead to improved clinical management. PMID- 22052625 TI - Identification of autosomal recessive disease loci using out-bred nuclear families. AB - Autozygosity mapping has been a powerful method for the identification of autosomal recessive disease genes. However, the approach is limited by the availability of suitable consanguineous pedigrees. While rare autosomal recessive diseases are overrepresented in consanguineous families, a significant proportion of affected patients nonetheless originate in families where the parents are apparently unrelated. However, due to their relative rarity and the heterogeneity of disease alleles, it has proved difficult to use these patients to identify disease loci. Therefore, we developed "Phaser," a computer application that is able to infer the phase of SNP alleles and so haplotype entire chromosomes in small nuclear families (http://dna.leeds.ac.uk/Phaser). Once the index case's chromosomes have been haplotyped, it is then possible to deduce those of the parents and subsequently identify the parental origin of all the siblings' DNA. By combining information from a small number of nuclear families, it may then be possible to identify linkage to the recessive disease locus, in both in-bred and out-bred families. We have illustrated the program's utility by using it to correctly identify both the cystic fibrosis locus (using two unrelated compound heterozygous CEPH families) and a new gene mutated in early-onset myopathy with respiratory distress and dysphagia locus in a single consanguineous pedigree. PMID- 22052626 TI - Surface modification of indium-tin-oxide via self-assembly of a donor-acceptor complex: a density functional theory study. AB - The authors study at the density-functional theory level the modification of the electronic structure of the ITO surface upon self-assembly of a monolayer of t butyl carbazole-substituted phosphonic acid molecules and subsequent p-doping. The results of the calculations point to the existence of two channels for charge transfer. These channels can enhance hole injection between ITO and a hole transport overlayer through the chemically-modified interface. PMID- 22052627 TI - Effects of low-level laser therapy in combination with physiotherapy in the management of rotator cuff tendinitis. AB - Rotator cuff tendinitis is one of the main causes of shoulder pain. The objective of this study was to evaluate the possible additive effects of low-power laser treatment in combination with conventional physiotherapy endeavors in these patients. A total of 50 patients who were referred to the Physical Medicine and Rehabilitation Clinic with shoulder pain and rotator cuff disorders were selected. Pain severity measured with visual analogue scale (VAS), abduction, and external rotation range of motion in shoulder joint was measured by goniometry, and evaluation of daily functional abilities of patients was measured by shoulder disability questionnaire. Twenty-five of the above patients were randomly assigned into the control group and received only routine physiotherapy. The other 25 patients were assigned into the experimental group and received conventional therapy plus low-level laser therapy (4 J/cm(2) at each point over a maximum of ten painful points of shoulder region for total 5 min duration). The above measurements were assessed at the end of the third week of therapy in each group and the results were analyzed statistically. In both groups, statistically significant improvement was detected in all outcome measures compared to baseline (p < 0.05). Comparison between two different groups revealed better results for control of pain (reduction in VAS average) and shoulder disability problems in the experimental group versus the control (3.1 +/- 2.2 vs. 5 +/- 2.6, p = 0.029 and 4.4 +/- 3.1 vs. 8.5 +/- 5.1, p = 0.031, respectively ) after intervention. Positive objective signs also had better results in the experimental group, but the mean range of active abduction (144.92 +/- 31.6 vs. 132.80 +/- 31.3) and external rotation (78.0 +/- 19.5 vs. 76.3 +/- 19.1) had no significant difference between the two groups (p = 0.20 and 0.77, respectively). As one of physical modalities, gallium-arsenide low-power laser combined with conventional physiotherapy has superiority over routine physiotherapy from the view of decreasing pain and improving the patient's function, but no additional advantages were detected in increasing shoulder joint range of motion in comparison to other physical agents. PMID- 22052629 TI - [Adolescents with cancer - administrative, clinical and scientific implications]. PMID- 22052628 TI - Normative performance on the executive clock drawing task in a multi-ethnic bilingual cohort: a project FRONTIER study. AB - BACKGROUND: The executive clock drawing task (CLOX) test is a neuropsychological measure intended to aid in the assessment and detection of dementia in older populations. Few studies have provided normative data for this measure, with even less research available regarding the impact of sociodemographic factors on test scores. This study presents normative data for the CLOX in a sample of English and Spanish-speaking Hispanic and non-Hispanic Whites. METHODS: The total sample included 445 cognitively healthy older adults seen as part of an ongoing study of rural cognitive aging, project FRONTIER. Unlike previous studies, criteria for "normality" (i.e., unimpaired) for CLOX1 and CLOX2 were based not merely on global impairment, but also on domain-specific impairment of executive functioning on the Executive Interview 25-item Examination and/or Trail Making Test B, or visuospatial/constructional impairment on the Line Orientation and Figure Copy subtests of the Repeatable Battery for the Assessment of Neuropsychological Status, respectively. RESULTS: Hierarchical regression analyses revealed that CLOX1 scores require adjustment by Age across ethnicities, whereas Education and Gender are necessary stratification markers for CLOX1 performance only in non-Hispanic Whites. None of the demographic variables were valid predictors of CLOX2 performance, negating the need for such adjustments. CONCLUSION: In addition to being the first study to provide separate normative data for CLOX performance in Hispanic and non-Hispanic White samples, the current study offers a novel approach to defining "normal" by cognitive domain. We also highlight the need to directly examine the impact of sociodemographic factors before applying normative corrections based on factors that have negligible impact on test scores. PMID- 22052630 TI - Hematopoietic stem cell transplantation for severe combined immunodeficiency. AB - Severe combined immunodeficiency (SCID) is a heterogeneous group of congenital diseases characterized by their presentation with life threatening infections in the first months of life. The clinical presentation and the therapeutic outcome is influenced by multiple factors: the genetic defect, infectious complications, the presence of maternal T cells the development of Omenn syndrome, as well as non-immunological signs and symptoms of the disease. Hematopoietic stem cell transplantation (HSCT) to date is the only established curative option and allows long-term cure of the disease. Therapeutic objectives of HSCT in SCID clearly differ from those in malignant or hematological disease. Disease specific aspects and their influence on the therapeutic strategy in SCID will be discussed in this review. PMID- 22052631 TI - Stem cell transplantation in 6 children with parvovirus B19- induced severe aplastic anaemia or myelodysplastic syndrome. AB - Parvovirus B19 (PVB19) induced severe aplastic anaemia (SAA) or myelodysplastic syndrome (MDS) is rare, and haematopoietic stem cell transplantation (HSCT) in this condition has not been reported so far. 6 children with SAA (n=4) or MDS (n=2) caused by acute PVB19 infection underwent HSCT under the protection of intravenous immunoglobulines. The 4 children with SAA received matched HLA bone marrow from a sibling (n=3) or peripheral unrelated blood stem cells (n=1). 1 patient had delayed erythrocyte engraftment, whereas 3 patients had an uneventful transplantation course. HSCT in one of the 2 children with MDS was complicated by poor graft function, the other patient engrafted without complications. In conclusion, HSCT in children with PVB19 induced SAA or MDS is feasible, even though some patients may develop delayed engraftment or prolonged poor graft function. PMID- 22052632 TI - Epileptic seizures after octreotide administration in a 6.5-year-old female with ALL and L-asparaginase associated pancreatitis: a possible drug interaction. AB - INTRODUCTION: Octreotide is a synthetic somatostatin analogue which has been suggested for use in the management of acute pancreatitis, though its safety and effectiveness in the pediatric setting has not been extensively studied. CASE REPORT: we present a rare case of a 6.5-year-old female with acute lymphoblastic leukemia (ALL) and L-asparaginase (L-asp) induced pancreatitis, who developed epileptic seizures, possibly associated with octreotide administration. Her imaging and laboratory findings ruled out a leukemic involvement or infection of CNS. The EEG revealed repetitive sharp waves maximal on the frontal and temporal areas of the right hemisphere. The child was treated with diazepam and she continued with systemic anticonvulsant treatment with levetiracetam. After 2 weeks of conservative treatment, pancreatitis resolved and she continued her chemotherapy protocol. Levetiracetam treatment lasted 8 months. 7 months after the first episode, EEG was reported as normal, and the child completed the chemotherapy protocol without any further severe complications. CONCLUSIONS: Larger and well designed studies are needed to warrant the safety of octreotide in pediatric population. PMID- 22052633 TI - Nodal anaplastic large-cell lymphoma ALK-1- with CD30+ cutaneous lymphoproliferation treated with mistletoe: spontaneous remission or treatment response? AB - A 12-year old girl presented with general weakness and weight loss, a localised cervical lymph node enlargement and cutaneous lesions compatible with lymphomatoid papulosis (LyP). Biopsies from lymph node and skin revealed a histological diagnosis of nodal large cell ALK-1- anaplastic lymphoma (ALCL) with a synchronous CD30+ cutaneous lymphoproliferation consistent with lymphomatoid papulosis (LyP). The girl was treated with mistletoe (MT) as monotherapy. Within 1 week after initiation of MT-treatment the skin lesions and lymph node enlargement improved. Under continuing MT-therapy 30 months after diagnosis the patient is still in complete remission. It is not possible to know whether this was a rare case of spontaneous remission of the nodal and skin-manifestations of this CD30+ T-cell lymphoproliferation or whether the observed effect was a specific therapeutic response to MT-treatment. PMID- 22052634 TI - Acute psychosis in an adolescent girl during treatment for advanced nodular lymphocyte-predominant Hodgkin's lymphom. AB - A 16,5 year old female adolescent was diagnosed with nodular lymphocyte predominant Hodgkin lymphoma (nLPHL), presenting bilateral inguinal and right iliac lymphadenopathy accompanied by B-symptoms. The patient was due to treatment according to the German Interim Guidelines of HD 2002-Pilot Study with 2x OPPA (vincristine, adriamycine, prednisone, procarbacine) and 2x COPP (cyclophosphamide, vincristine, prednisone, procarbazine) and radiotherapy. After 2x OPPA the patient presented a severe episode of a presumably prednisone-induced acute psychosis with need for psychiatric treatment and change of therapy regimen. She was successfully treated with a chimeric monoclonal anti-CD20 antibody (rituximab) and subsequent radiotherapy. PMID- 22052635 TI - Long-term follow-up of morbidly obese patients with childhood craniopharyngioma after laparoscopic adjustable gastric banding (LAGB). PMID- 22052636 TI - Palliative sedation in 2 children with terminal cancer - an effective treatment of last resort in a home care setting. PMID- 22052637 TI - Idiopathic pulmonary hemosiderosis - a severe differential diagnosis of diffuse alveolar hemorrhage. PMID- 22052638 TI - [Interdisciplinary AWMF guideline for the diagnostics of primary immunodeficiency]. AB - BACKGROUND: Primary immunodeficiencies are potentially life-threatening diseases. Over the last years, the clinical phenotype and the molecular basis of an increasing number of immunological defects have been characterized. However, in daily practice primary immunodeficiencies are still often diagnosed too late. Considering that an early diagnosis may reduce morbidity and mortality of affected patients, an interdisciplinary guideline for the diagnosis of primary immunodeficiencies was developed on behalf of the Arbeitsgemeinschaft Padiatrische Immunologie (API) and the Deutsche Gesellschaft fur Immunologie (DGfI). METHODS: The guideline is based on expert opinion and on knowledge from other guidelines and recommendations from Germany and other countries, supplemented by data from studies that support the postulated key messages (level of evidence III). With the contribution of 20 representatives, belonging to 14 different medical societies and associations, a consensus-based guideline with a representative group of developers and a structured consensus process was created (S2k). Under the moderation of a representative of the Association of the Scientific Medical Societies in Germany (AWMF) the nominal group process took place in April 2011. RESULTS: The postulated key messages were discussed and voted on following a structured consensus procedure. In particular, modified warning signs for primary immunodeficiencies were formulated and immunological emergency situations were defined. PMID- 22052639 TI - OMIP-004: in-depth characterization of human T regulatory cells. PMID- 22052640 TI - Flexible metal-organic framework with hydrophobic pores. PMID- 22052641 TI - Pediatric disk herniation. AB - Pediatric disk herniation is a rare condition that should be considered in the differential diagnosis of the child with back pain or radiating leg pain. Because pediatric disk herniation is relatively uncommon, there is typically a delay in diagnosis compared with time to diagnosis of adult disk herniation. Pediatric disk herniations are often recalcitrant to nonsurgical care, but such measures should be attempted in patients who present with isolated pain symptoms and have a normal neurologic examination. Twenty-eight percent of adolescent disk herniations involve apophyseal fractures; this presentation has a higher rate of surgical intervention than do herniations without fracture. Surgical management of pediatric disk herniation involves laminotomy and fragment excision. Short term data demonstrate excellent pain relief, with 1% of children requiring repeat surgery for lumbar disk pathology in the first year. Long-term data suggest that 20% to 30% of patients will require additional surgery later in life. PMID- 22052642 TI - Arthroscopic revision rotator cuff repair. AB - Rotator cuff repair leads to good and excellent outcomes in most patients. However, structural failure of the repair occurs in a substantial number of cases and can lead to an unsatisfactory result. Several factors have been implicated, including patient-related factors (eg, patient age, tear size) and extrinsic factors (eg, surgeon surgical volume, biomechanical failure). Structural failure requires a detailed patient evaluation to elucidate the cause of persistent symptoms. Function can be maintained despite a recurrent tear; therefore, a recurrent tear alone is not an indication for revision repair. The major indication for revision rotator cuff repair is the persistence of clinical symptoms, despite nonsurgical management, in the absence of substantial risk factors for failure. Although the outcome is poorer than after primary repair, satisfactory results have been reported following revision repair of recurrent rotator cuff tears, particularly with arthroscopic techniques. PMID- 22052643 TI - Surgical management of healed slipped capital femoral epiphysis. AB - Slipped capital femoral epiphysis (SCFE) results in posterior and inferior displacement of the epiphysis on the femoral neck. In most centers, the recommended initial management of stable SCFE is in situ pinning. Minimal reduction with in situ pinning is recommended for unstable SCFE. This approach does not restore the normal anatomy of the hip joint, and the resulting proximal femoral deformity may cause femoroacetabular impingement. Patients with femoroacetabular impingement experience reduced hip range of motion as well as hip pain, and they are at risk of early-onset hip osteoarthritis. Techniques for managing this deformity include arthroscopic femoral neck osteochondroplasty, a limited anterior hip approach or surgical hip dislocation, and flexion intertrochanteric osteotomy. These surgical techniques should be considered for patients with healed SCFE deformity who present with hip pain at an early age. PMID- 22052644 TI - Osteoid osteoma and osteoblastoma. AB - Osteoid osteoma and osteoblastoma are commonly seen benign osteogenic bone neoplasms. Both tumors are typically seen in the second decade of life, with a notable predilection in males. Histologically, these tumors resemble each other, with characteristically increased osteoid tissue formation surrounded by vascular fibrous stroma and perilesional sclerosis. However, osteoblastomas are larger than osteoid osteomas, and they exhibit greater osteoid production and vascularity. Clinically, osteoid osteoma most commonly occurs in the long bones (eg, femur, tibia). The lesions cause night pain that is relieved with nonsteroidal anti-inflammatory drugs (NSAIDs). Osteoblastoma is most frequently located in the axial skeleton, and the pain is usually not worse at night and is less likely to be relieved with NSAIDs. Osteoblastoma can be locally aggressive; osteoid osteoma lacks growth potential. Osteoid osteoma may be managed nonsurgically with NSAIDs. When surgery is required, minimally invasive methods (eg, CT-guided excision, radiofrequency ablation) are preferred. Osteoblastoma has a higher rate of recurrence than does osteoid osteoma, and patients must be treated surgically with intralesional curettage or en bloc resection. PMID- 22052645 TI - Intramedullary nailing of extra-articular proximal tibia fractures. AB - Tibial fractures are the most common long bone fractures. Extra-articular proximal tibia fractures account for approximately 5% to 11% of all tibial shaft fractures. The benefits of intramedullary nailing of these fractures include load sharing, sparing of the extraosseous blood supply, and avoidance of additional soft-tissue dissection, thereby minimizing the risk of postoperative complications. A significant rate of malalignment has been reported with intramedullary nailing of proximal tibia fractures, however. Malalignment typically presents as apex anterior and valgus angulation. Several nailing methods and reduction techniques have been developed to minimize this complication, including the use of a proper starting point and insertion angle, blocking screws, unicortical plates, a universal distractor, and alternative positioning and approaches. Use of one or more of these techniques has resulted in a reported average malreduction rate of 8.2%. PMID- 22052646 TI - Subacromial impingement syndrome. AB - Subacromial impingement syndrome (SIS) represents a spectrum of pathology ranging from subacromial bursitis to rotator cuff tendinopathy and full-thickness rotator cuff tears. The relationship between subacromial impingement and rotator cuff disease in the etiology of rotator cuff injury is a matter of debate. Both extrinsic compression and intrinsic degeneration may play a role. Management includes physical therapy, injections, and, for some patients, surgery. There remains a need for high-quality studies of the pathology, etiology, and management of SIS. PMID- 22052647 TI - Arthroscopic releases for arthrofibrosis of the knee. AB - Intra-articular inflammation or fibrosis may lead to decreased soft-tissue and capsular compliance, which may result in pain or loss of motion within the knee. Etiology of intra-articular fibrosis may include isolated anterior interval scarring and posterior capsular contracture, as well as fibrosis that involves the suprapatellar pouch or arthrofibrosis that involves the entire synovial space. Initial nonsurgical management, including compression, elevation, and physical therapy, can decrease knee pain and inflammation and maintain range of motion. Surgical management is indicated in the patient who fails conservative treatment. Surgical options include arthroscopic releases of the anterior interval, posterior capsule, and peripatellar and suprapatellar regions. Recent advances in arthroscopic technique have led to improved outcomes in patients with intra-articular fibrosis of the knee. PMID- 22052648 TI - Epidemiology of hepatitis B and hepatitis C virus infections among hemodialysis patients in Khartoum, Sudan. AB - The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) is important for health planners and service providers. A cross-sectional study was conducted to investigate the seroprevalence and associated risk factors for markers of HBV (HBsAg) and anti-HCV among hemodialysis patients at the Ahmed Gasim hemodialysis unit, Sudan. Structured questionnaires were used to obtain socio-demographic data and sera were tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV). Of the 353 patients enrolled in the study, HBsAg and anti-HCV were detected in 16 (4.5%) and 30 (8.5%) patients, respectively. None of the patients were co-infected with HBV and HCV. Multivariate analysis showed that duration of dialysis was significantly associated with anti-HCV seropositivity [OR = 1.1, 95% CI = 1.2-1.3; P = 0.024]. No other socio-demographic or clinical characteristics (age, sex, level of education, history of surgery, and number of units of blood transfused) were significantly associated with HBsAg or anti-HCV seropositivity. The results of this study suggest that HBsAg and anti-HCV have low prevalence among hemodialysis patients in Khartoum. Longer duration of dialysis was a risk factor for anti-HCV. PMID- 22052650 TI - Experience with use of Zostavax((r)) in patients with hematologic malignancy and hematopoietic cell transplant recipients. PMID- 22052649 TI - Combined p53-related genetic variants together with HPV infection increase oral cancer risk. AB - To explore the role of polymorphisms of p53-related genes in etiology of oral cancer, we investigated joint effects of seven putatively functional polymorphisms of p53 (codon 72 Arg/Pro), p73 (4/14 GC/AT), murine double minute 2 gene (MDM2; A2164G and T2580G) and MDM4 (rs11801299 G > A, rs10900598 G > T and rs1380576 C > G) on risk of human papillomavirus (HPV)16-associated oral cancer in a case-control study with 325 cases and 335 cancer-free controls. We found that HPV16 seropositivity alone was associated with an increased risk of oral cancer [adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6]. After combining genotypes of seven polymorphisms and using the low-risk group (0 3 combined risk genotypes) and HPV16 seronegativity as the reference group, the medium-risk (4 combined risk genotypes) and high-risk groups (5-7 combined risk genotypes) and HPV16 seronegativity were associated with only an OR of 1.6 (95% CI, 1.1-2.5) and 1.2 (95% CI, 0.7-1.9) for oral cancer risk, respectively, whereas the low-risk, medium-risk and high-risk groups and HPV16 seropositivity were significantly associated with a higher OR of 2.1 (95% CI, 1.2-3.6), 4.0 (95% CI, 1.8-9.1) and 19.1 (95% CI, 5.7-64.2), respectively. Notably, such effect modification by these combined risk genotypes was particularly pronounced in young subjects (aged < 50 years), never smokers and patients with oropharyngeal cancer. Taken together, these findings suggest that the combined risk genotypes of p53-related genes may modify risk of HPV16-associated oral cancer, especially in young patients, never-smokers and patients with oropharyngeal cancer. Larger studies are needed to validate our findings. PMID- 22052651 TI - Photocrosslinkable polyesters and poly(ester anhydride)s for biomedical applications. AB - Crosslinking is a feasible way to prepare biodegradable polymers with potential in biomedical applications such as controlled release of active agents and tissue engineering. A synthesis route in which functional telechelic aliphatic polyester oligomers are used as precursors for the preparation of crosslinked polyesters and poly(ester anhydride)s is described. Mechanical properties, degradation characteristics and rate, and bioactivity can be modified widely by controlling the chemical composition and architecture of the crosslinkable oligomers. In tissue engineering, photocrosslinking allows to use crosslinkable oligomers in advanced manufacturing techniques like micromolding in capillaries, stereolithography and two-photon polymerization. PMID- 22052652 TI - The golden age of GPCR structural biology: any impact on drug design? PMID- 22052653 TI - Optimization of a parallel artificial membrane permeability assay for the fast and simultaneous prediction of human intestinal absorption and plasma protein binding of drug candidates: application to dibenz[b,f]azepine-5-carboxamide derivatives. AB - Parallel artificial membrane permeability assay (PAMPA) has been successfully applied by pharmaceutical industries as high-throughput technique capable of screening compounds for passive oral absorption. Herein, the possible applicability of this assay to predict simultaneously biodistribution parameters such as plasma protein binding (PPB) and apparent volume of distribution (VD) was investigated for the first time. Apparent permeability (P(app) ) of 18 reference drugs was determined by nine PAMPA conditions and compared with the corresponding intestinal absorption fraction (Fa), PPB, and VD in humans. In all the models, P(app) was not correlated with VD; however, it was correlated with Fa and PPB. In these cases, the best correlations (r >= 0.8953) were found when using a membrane of 2% of l-alpha-phosphatidylcholine, at pH 6.5/7.4 for donor/acceptor compartments. Under these conditions, good correlation with traditional PAMPA (r = 0.9633) and Caco-2 models (r = 0.9246) were also achieved. This method correctly predicted compounds' permeability and was robust enough to distinguish compounds with high Fa (P(app) >= 1.1 * 10(-6) cm/s) and PPB (P(app) >= 1.0 * 10( 5) cm/s), with no false positives or negatives recorded. In addition, ultrafiltration method was used to determine the PPB of 10 tested derivatives of dibenz[b,f]azepine-5-carboxamide, which were also assessed through the new PAMPA model developed herein, and equal classifications were achieved. PMID- 22052654 TI - Antioxidant effect of propolis against exposure to chromium in Cyprinus carpio. AB - The aim of the present study was to investigate the ameliorative properties of propolis against the toxic effects of chromium (VI) by examining oxidative damage markers such as lipid peroxidation and the antioxidant defence system components in carp (Cyprinus carpio). The fish were exposed to sublethal concentrations of chromium. Propolis was simultaneously administered to chromium-exposed fish. Treatment was continued for 28 days, and at the end of this period, blood and tissue (liver, kidney, spleen, and gill) samples were collected. Levels of malondialdehyde (MDA) and reduced glutathione (GSH) as well as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were determined in blood and tissues for measurement of oxidant-antioxidant status. The levels of MDA, as an index of lipid peroxidation, increased in blood and tissues. Antioxidant enzyme activities in blood and tissues were modified in chromium groups compared to controls. Simultaneous administration of propolis ameliorated these parameters. The present results suggest that administration of propolis might alleviate chromium-induced oxidative stress. PMID- 22052655 TI - A novel familial 11p15.4 microduplication associated with intellectual disability, dysmorphic features, and obesity with involvement of the ZNF214 gene. AB - We evaluated a patient with mild intellectual disability, obesity, overgrowth, and dysmorphic features. Array comparative genomic hybridization (aCGH) analysis showed a single copy number increase of a BAC clone in the 11p15.4 region. Oligonucleotide aCGH refined the duplication to approximately 2.29 megabases (Mb) in size. Testing the parents revealed that the father, who had learning disabilities and overgrowth, also had the 11p15.4 duplication, and the mother had a normal microarray. In addition, the patient's brother and grandmother all share clinical features with the proband and tested positive for the duplication. The duplicated region (Chr11:6,934,067-9,220,605) encompasses 29 genes, including the ZNF214 gene, which has been postulated to play a role in Beckwith-Wiedemann syndrome [Alders et al., 2000]. This three-generation pedigree outlines features of a novel microduplication syndrome. PMID- 22052656 TI - Growth, physiological and molecular traits in Salicaceae trees investigated for phytoremediation of heavy metals and organics. AB - Worldwide, there are many large areas moderately contaminated with heavy metals and/or organics that have not been remediated due to the high cost and technical drawbacks of currently available technologies. Methods with a good potential for coping with these limitations are emerging from phytoremediation techniques, using, for example, specific amendments and/or plants selected from various candidates proven in several investigations to be reasonably efficient in extracting heavy metals from soil or water, or in co-metabolizing organics with bacteria flourishing or inoculated in their rhizospheres. Populus and Salix spp., two genera belonging to the Salicaceae family, include genotypes that can be considered among the candidates for this phytoremediation approach. This review shows the recent improvements in analytical tools based on the identification of useful genetic diversity associated with classical growth, physiological and biochemical traits, and the importance of plant genotype selection for enhancing phytoremediation efficiency. Particularly interesting are studies on the application of the phytoremediation of heavy metals and of chlorinated organics, in which microorganisms selected for their degradation capabilities were bioaugmented in the rhizosphere of Salicaceae planted at a high density for biomass and bioenergy production. PMID- 22052657 TI - Characterization of a novel biosurfactant produced by Staphylococcus sp. strain 1E with potential application on hydrocarbon bioremediation. AB - A biosurfactant-producing bacterium (Staphylococcus sp. strain 1E) was isolated from an Algerian crude oil contaminated soil. Biosurfactant production was tested with different carbon sources using the surface tension measurement and the oil displacement test. Olive oil produced the highest reduction in surface tension (25.9 dynes cm(-1)). Crude oil presented the best substrate for 1E biosurfactant emulsification activity. The biosurfactant produced by strain 1E reduced the growth medium surface tension below 30 dynes cm(-1). This reduction was also obtained in cell-free filtrates. Biosurfactant produced by strain 1E showed stability in a wide range of pH (from 2 to 12), temperature (from 4 to 55 degrees C) and salinity (from 0 to 300 g l(-1)) variations. The biosurfactant produced by strain 1E belonged to lipopeptide group and also constituted an antibacterial activity againt the pathogenic bacteria such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis. Phenanthrene solubility in water was enhanced by biosurfactant addition. Our results suggest that the 1E biosurfactant has interesting properties for its application in bioremediation of hydrocarbons contaminated sites. PMID- 22052659 TI - Guidelines for establishing locus specific databases. AB - Information about genetic variation has been collected for some 20 years into registries, known as locus specific databases (LSDBs), which nowadays often contain information in addition to the actual genetic variation. Several issues have to be taken into account when considering establishing and maintaining LSDBs and these have been discussed previously in a number of articles describing guidelines and recommendations. This information is widely scattered and, for a newcomer, it would be difficult to obtain the latest information and guidance. Here, a sequence of steps essential for establishing an LSDB is discussed together with guidelines for each step. Curators need to collect information from various sources, code it in systematic way, and distribute to the research and clinical communities. In doing this, ethical issues have to be taken into account. To facilitate integration of information to, for example, analyze genotype-phenotype correlations, systematic data representation using established nomenclatures, data models, and ontologies is essential. LSDB curation and maintenance comprises a number of tasks that can be managed by following logical steps. These resources are becoming ever more important and new curators are essential to ensure that we will have expertly curated databases for all disease related genes in the near future. PMID- 22052658 TI - Validation of potential classification criteria for systemic sclerosis. AB - OBJECTIVE: Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated jointly by the American College of Rheumatology and European League Against Rheumatism. Potential items for classification were reduced to 23 using Delphi and nominal group techniques. We evaluated the face, discriminant, and construct validity of the items to be further studied as potential criteria. METHODS: Face validity was evaluated using the frequency of items in patients sampled from the Canadian Scleroderma Research Group, 1000 Faces of Lupus, and the Pittsburgh, Toronto, Madrid, and Berlin connective tissue disease (CTD) databases. Patients with SSc (n = 783) were compared to 1,071 patients with diseases similar to SSc (mimickers): systemic lupus erythematosus (n = 499), myositis (n = 171), Sjogren's syndrome (n = 95), Raynaud's phenomenon (RP; n = 228), mixed CTD (n = 29), and idiopathic pulmonary arterial hypertension (PAH; n = 49). Discriminant validity was evaluated using odds ratios (ORs). For construct validity, empirical ranking was compared to expert ranking. RESULTS: Compared to mimickers, patients with SSc were more likely to have skin thickening (OR 427); telangiectasias (OR 91); anti-RNA polymerase III antibody (OR 75); puffy fingers (OR 35); finger flexion contractures (OR 29); tendon/bursal friction rubs (OR 27); anti-topoisomerase I antibody (OR 25); RP (OR 24); fingertip ulcers/pitting scars (OR 19); anticentromere antibody (OR 14); abnormal nailfold capillaries (OR 10); gastroesophageal reflux disease symptoms (OR 8); antinuclear antibody, calcinosis, dysphagia, and esophageal dilation (all OR 6); interstitial lung disease/pulmonary fibrosis (OR 5); and anti-PM-Scl antibody (OR 2). Reduced carbon monoxide diffusing capacity, PAH, and reduced forced vital capacity had ORs of <2. Renal crisis and digital pulp loss/acroosteolysis did not occur in SSc mimickers (OR not estimated). Empirical and expert ranking were correlated (Spearman's rho = 0.53, P = 0.01). CONCLUSION: The candidate items have good face, discriminant, and construct validity. Further item reduction will be evaluated in prospective SSc and mimicker cases. PMID- 22052660 TI - Allylsilanes in "tin-free" oximation, alkenylation, and allylation of alkyl halides. AB - Tin-free oximation, vinylation, and allylation of alkyl halides have been developed by using allylsilanes as di-tin surrogates. Initiation of the radical process with a peroxide provides the silyl radical, which can abstract a halogen from the corresponding alkyl halide. The resulting carbon-centered radical then adds to various acceptors, including a sulfonyloxime, a vinylsulfone, and an allylsulfone, leading to formation of the desired products along with the corresponding allylsulfone resulting from the reaction of the PhSO(2) radical with the allylsilane precursor. Better results were generally obtained with methallylsilane 1b than with 1a. This observation was rationalized by invoking the higher nucleophilicity of 1b and the faster beta-fragmentation of the corresponding beta-silyl radical intermediate. Calculation of the energy barrier for the beta-fragmentation of a series of beta-silyl radicals at the DFT level supported this hypothesis. Finally, a second version of these oximation and vinylation reactions, based on the utilization of 3 tris(trimethylsilyl)silylthiopropene, was devised, affording the desired oximes and olefins in reasonable yields. This strategy allowed the title reaction to be performed under milder conditions (AIBN, benzene, 80 degrees C), as a result of the easier beta-fragmentation of the C-S bond as compared with the C-Si bond. PMID- 22052661 TI - 2D sandwich-like sheets of iron oxide grown on graphene as high energy anode material for supercapacitors. AB - 2D sandwich-like sheets of iron oxide grown on graphene as high energy anode material for supercapacitors are prepared from the direct growth of FeOOH nanorods on the surface of graphene and the subsequent electrochemical transformation of FeOOH to Fe(3)O(4). The Fe(3)O(4) @RGO nanocomposites exhibit superior capacitance (326 F g(-1)), high energy density (85 Wh kg(-1)), large power, and good cycling performance in 1 mol L(-1) LiOH solution. PMID- 22052663 TI - Evolution of Anelloviridae strains distribution in serial blood and biopsy samples from a renal transplant patient. AB - A few studies investigated the natural history of viruses belonging to the family Anelloviridae in transplant patient. The case of a 64-year-old kidney transplant recipient is described. Molecular analysis of serial blood samples collected before and after transplant was performed during a period of 510 days. Two kidney biopsies were also analyzed. All blood samples tested positive for Anelloviridae DNA, with the identification of sequences belonging to the three taxonomic genera identified in humans. Sequences distribution during the follow-up was multimodal. A sequence nearly identical to one present in the blood before transplant was further characterized in one biopsy sample. PMID- 22052662 TI - Electrocardiographic consequences of cardiac iron overload in thalassemia major. AB - Iron cardiomyopathy is a leading cause of death in transfusion-dependent thalassemia major (TM) patients and MRI (T2*) can recognize preclinical cardiac iron overload, but, is unavailable to many centers. We evaluated the ability of 12-lead electrocardiography to predict cardiac iron loading in TM. 12-lead electrocardiogram and cardiac T2* measurements were performed prospectively, with a detectable cardiac iron cutoff of T2*less than 20 ms. Patients with and without cardiac iron were compared using two-sample statistics and against population norms using age and gender-matched Z-scores. 45/78 patients had detectable cardiac iron. Patients having cardiac iron were older and more likely female but had comparable liver iron burdens and serum ferritin. Increased heart rate (HR) and prolonged corrected QT interval (QT(c)) were present, regardless of cardiac iron status. Repolarization abnormalities were the strongest predictors of cardiac iron, including QT/QT(c) prolongation, left shift of T-wave axis, and interpretation of ST/T-wave morphology. Recursive partitioning of the data for females using T-axis and HR and for males using QT, HR, and T-axis produced algorithms with AUROC's of 88.3 and 87.1, respectively. Bradycardia and repolarization abnormalities on 12-lead electrocardiography were the most specific markers for cardiac iron in thalassemia major. Changes in these variables may be helpful to stratify cardiac risk when cardiac MRI is unavailable. However, diagnostic algorithms need to be vetted on larger and more diverse patient populations and longitudinal studies are necessary to determine reversibility of the observed abnormalities. PMID- 22052664 TI - Silymarin prevents the toxicity induced by benzo(a)pyrene in human erythrocytes by preserving its membrane integrity: an in vitro study. AB - Silymarin, the purified extract from milk thistle Silybum marianum (L.) Gaertn, consists mainly of four isomeric flavonolignans: silibinin, isosilibinin, silidianin, and silichristin. The present study was carried out to evaluate the protective potential of silymarin in human erythrocytes against in vitro exposure to the carcinogen benzo(a)pyrene (B(a)P). Erythrocytes isolated from human blood were divided into four groups and treated with Vehicle [Group I], B(a)P (300 MUM) [Group II], Silymarin (500 MUM) + B(a)P (300 MUM) [Group III], and Silymarin alone (500 MUM)] [Group IV]. Silymarin treatment maintains the integrity of erythrocytes by preventing hemolysis, protein thiol oxidation and by decreasing the activity of AChE. SEM observations indicate that B(a)P induced significant alteration in the morphology of erythrocytes to echinocytes, which may be due to the interaction of B(a)P with the membrane's outer phopholipid monolayer. The light microscopic and SEM images show that silymarin treatment maintains the normal discocytic morphology of erythrocytes. The protective effect of silymarin might be attributed to its chemical structure and membranotrophic nature. The components silibinin, silydianin, and silychristin have OH in the 3rd, 5th, and 7th carbon atoms that may account for its increased antioxidant activity and removal of ROS formed during B(a)P metabolism. PMID- 22052665 TI - Preparative separation of methylswertianin, swerchirin and decussatin from the Tibetan medicinal plant Swertia mussotii using high-speed counter-current chromatography. AB - INTRODUCTION: Xanthones, the primary constituents of Swertia mussotii, are known to possess a variety of biological activities, including anti-depressant, anti leukaemic, anti-tumour, anti-tubercular, choleretic, diuretic, anti-microbial, anti-fungal, anti-inflammatory, anti-viral, cardiotonic and hypoglycemic properties. However, high performance, environmentally friendly methods for isolating and purifying xanthones from S. mussotii are not currently available. OBJECTIVE: To develop a high performance and environmentally friendly method for the preparative separation of xanthones methylswertianin, swerchirin and decussatin from S. mussotii using high-speed counter-current chromatography (HSCCC). METHODOLOGY: A solvent system composed of n-hexane:ethyl acatate:methanol:water (5:5:10:4, v/v/v/v) was developed for the separation method. The upper phase was used as the stationary phase, and the lower phase was used as the mobile phase at a flow rate of 1.5 mL/min, a rotation speed of 800 rpm and a temperature of 25 degrees C. RESULTS: Using the described method, 8 mg of methylswertianin, 21 mg of swerchirin and 11 mg of decussatin with purities of over 98% could be isolated from a 150 mg crude sample. They were identified by 1H NMR and 13C-NMR analysis. CONCLUSION: Three xanthones in Swertia mussotii could be systematically isolated and purified using HSCCC. PMID- 22052666 TI - Chromosomally integrated human herpesvirus 6: questions and answers. AB - Chromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease. PMID- 22052667 TI - Producing cell-free culture broth of rhamnolipids as a cost-effective fungicide against plant pathogens. AB - Biosurfactants of rhamnolipids have been enthusiastically investigated for substitutes of synthetic agrochemicals against plant pathogens. However, all such studies have been conducted on rhamnolipids with high purity which have limitations due to high costs. This paper focused on the applicability of rhamnolipid-containing cell-free culture broth. It was found that rhamnolipids in cell-free culture broth of Pseudomonas aeruginosa ZJU211 were largely composed of di-rhamnolipid and mono-rhamnolipid with the ratio varying with culture time. After 96 h of fermentation, the mass ratio of di-rhamnolipid over mono rhamnolipid increased to 2.6:1. Crude rhamnolipids in a form of cell-free culture broth showed high antifungal activity against colony growth and biomass accumulation of seven plant pathogens comprising two Oomycetes, three Ascomycota and two Mucor spp. fungi, among which three plant pathogens were firstly reported in this paper showing inhibition to rhamnolipids. Particularly, rhamnolipids showed potent activity against two Oomycetes that acquire resistance to commercial compound of metalaxyal. Furthermore, di-rhamnolipid was elucidated to dominate the antifungal activity of crude rhamnolipids by in vitro studies. At last, the efficacy and safety of cell-free culture broth was preliminarily illustrated on plants in vivo. So cell-free culture broth as a crude rhamnolipid product could be served as a potential cost-effective and environmental-friendly fungicide in agriculture. PMID- 22052669 TI - Reversing the reactivity of carbonyl functions with phosphonium salts: enantioselective total synthesis of (+)-centrolobine. PMID- 22052670 TI - Acrofrontofacionasal dysostosis 1 in two sisters of Indian origin. PMID- 22052668 TI - Identification of a mutation causing deficient BMP1/mTLD proteolytic activity in autosomal recessive osteogenesis imperfecta. AB - Herein, we have studied a consanguineous Egyptian family with two children diagnosed with severe autosomal recessive osteogenesis imperfecta (AR-OI) and a large umbilical hernia. Homozygosity mapping in this family showed lack of linkage to any of the previously known AR-OI genes, but revealed a 10.27 MB homozygous region on chromosome 8p in the two affected sibs, which comprised the procollagen I C-terminal propeptide (PICP) endopeptidase gene BMP1. Mutation analysis identified both patients with a Phe249Leu homozygous missense change within the BMP1 protease domain involving a residue, which is conserved in all members of the astacin group of metalloproteases. Type I procollagen analysis in supernatants from cultured fibroblasts demonstrated abnormal PICP processing in patient-derived cells consistent with the mutation causing decreased BMP1 function. This was further confirmed by overexpressing wild type and mutant BMP1 longer isoform (mammalian Tolloid protein [mTLD]) in NIH3T3 fibroblasts and human primary fibroblasts. While overproduction of normal mTLD resulted in a large proportion of proalpha1(I) in the culture media being C-terminally processed, proalpha1(I) cleavage was not enhanced by an excess of the mutant protein, proving that the Phe249Leu mutation leads to a BMP1/mTLD protein with deficient PICP proteolytic activity. We conclude that BMP1 is an additional gene mutated in AR-OI. PMID- 22052671 TI - Nanoscale in situ characterization of Li-ion battery electrochemistry via scanning ion conductance microscopy. AB - Scanning ion conductance microscopy imaging of battery electrodes, using the geometry shown in the figure, is a tool for in situ nanoscale mapping of surface topography and local ion current. Images of silicon and tin electrodes show that the combination of topography and ion current provides insight into the local electrochemical phenomena that govern the operation of lithium ion batteries. PMID- 22052672 TI - Determinants of discordance in patients' and physicians' rating of rheumatoid arthritis disease activity. AB - OBJECTIVE: To assess the determinants of patients' (PTGL) and physicians' (MDGL) global assessment of rheumatoid arthritis (RA) activity and factors associated with discordance among them. METHODS: A total of 7,028 patients in the Quantitative Standard Monitoring of Patients with RA study had PTGL and MDGL assessed at the same clinic visit on a 0-10-cm visual analog scale (VAS). Three patient groups were defined: concordant rating group (PTGL and MDGL within +/-2 cm), higher patient rating group (PTGL exceeding MDGL by >2 cm), and lower patient rating group (PTGL less than MDGL by >2 cm). Multivariable regression analysis was used to identify determinants of PTGL and MDGL and their discordance. RESULTS: The mean +/- SD VAS scores for PTGL and MDGL were 4.01 +/- 2.70 and 2.91 +/- 2.37, respectively. Pain was overwhelmingly the single most important determinant of PTGL, followed by fatigue. In contrast, MDGL was most influenced by swollen joint count (SJC), followed by erythrocyte sedimentation rate (ESR) and tender joint count (TJC). A total of 4,454 (63.4%), 2,106 (30%), and 468 (6.6%) patients were in the concordant, higher, and lower patient rating groups, respectively. Odds of higher patient rating increased with higher pain, fatigue, psychological distress, age, and morning stiffness, and decreased with higher SJC, TJC, and ESR. Lower patient rating odds increased with higher SJC, TJC, and ESR, and decreased with lower fatigue levels. CONCLUSION: Nearly 36% of patients had discordance in RA activity assessment from their physicians. Sensitivity to the "disease experience" of patients, particularly pain and fatigue, is warranted for effective care of RA. PMID- 22052673 TI - A discriminating dissolution method for glimepiride polymorphs. AB - Glimepiride, an oral antidiabetic drug, is practically insoluble in water and exists in two polymorphic forms, I and II, of which form II has higher solubility in water. Because the dissolution rate of drugs can depend on the crystal form, there is a need to develop discriminating dissolution methods that are sensitive to changes in polymorphic forms. In this work, a dissolution method for the assessment of 4 mg glimepiride tablets was developed and validated. The optimal dissolution conditions were 1000 mL of phosphate buffer (pH 6.8) containing 0.1% (w/v) of sodium dodecyl sulfate as the dissolution medium and a stirring speed of 50 rpm using a paddle apparatus. The results demonstrated that all the data meet the validation acceptance criteria. Subsequently, tablets containing forms I and II of glimepiride were prepared and subjected to dissolution testing. A significant influence of polymorphism on the dissolution properties of glimepiride tablets was observed. These results suggested that the raw material used to produce glimepiride tablets must be strictly controlled because they may produce undesirable and unpredictable effects. PMID- 22052674 TI - Tuning size scale and crystallinity of PCL electrospun fibres via solvent permittivity to address hMSC response. AB - The effect of solvent permittivity on the fibre morphology of PCL electrospun membranes for tissue engineering applications is studied. Morphological results indicate that polar solvents with higher permittivity are able to promote the formation of sub-micrometric fibres, while apolar solvents yield microfibres with an average fibre diameter of 2.86 +/- 0.31 um. Polymer/solvent interactions and electrospinning process parameters influence the mechanism of fibre and bead formation. It is shown that the dielectric properties of solvents influence the fibre size scale and crystallinity and directly contribute to the biological response of stem cells. Solvent permittivity is a key factor in controlling the morphological and physical properties of electrospun fibre meshes. PMID- 22052675 TI - Thrombin generation reveals high procoagulant potential in the plasma of sickle cell disease children. AB - Changes in several components of the clotting system are well documented in sickle cell disease (SCD) patients. However, whether the global hemostatic potential of these patients is altered is still unclear. Calibrated automated thrombogram((r)) method of thrombin generation (TG) was used to characterize the hemostatic potential of 83 SCD children (75 SS, 6 SC, and 2 Sbeta (thal)) at steady-state as compared with 50 controls of the same range of age. TG was triggered using 1 pM tissue factor and 4 MUM phospholipids with and without thrombomodulin. Thirteen SCD children were also evaluated during vaso-occlusive crisis. Protein C activity, free protein S and D-dimers levels were measured in parallel. SCD patients showed higher rates of thrombin formation, higher thrombin peak height (with and without thrombomodulin), and higher endogenous thrombin potential (ETP) than controls in the presence of thrombomodulin. Reduction of ETP (RETP) in the presence of thrombomodulin was lower in SCD group compared with controls and correlated both with protein C and protein S levels. ETP, RETP, peak height, and velocity index of TG correlated with D-dimers. Compound heterozygous patients showed an intermediate hemostatic phenotype at steady-state. No significant difference was observed when comparing TG parameters during vaso occlusive crisis to those obtained at steady-state in the same patients. The global hemostatic potential is increased and reflects the hypercoagulable state of SCD patients even at steady-state. The relevance of this finding with respect to the risk of thrombotic complications of the disease needs further investigation. PMID- 22052676 TI - Multifunctional and reactive enantiopure organometallic helicenes: tuning chiroptical properties by structural variations of mono- and bis(platinahelicene)s. AB - Acetylacetonato-platina[6]- and -platina[7]helicenes have been prepared from 2 pyridyl-substituted benzophenanthrene ligands by following a two-step cycloplatination reaction. The photophysical properties (UV-visible absorption and emission behavior) and chiroptical properties (circular dichroism and molar rotation) of the resolved enantiomers have been measured. These metallahelicenes constitute a novel family of easily accessible helicene derivatives that exhibit large and tuneable chiroptical properties that can be rationalized theoretically and compared to the parent [6]- and [7]carbohelicenes. Furthermore, they are red phosphors at room temperature and their large chiroptical properties can be modulated by oxidation of the metal center to Pt(IV). Hetero- and homochiral diastereomeric bis(metallahelicene)s that possess a rare Pt(III)-Pt(III) scaffold bridged by benzoato ligands have also been prepared. It is shown that the heterochiral (P,M)-bis(Pt(III)-[6]helicene) 9a(1) can isomerize into the homochiral (P,P)- and (M,M)-bis(Pt(III)-[6]helicene) 9a(2). Spectral assignments and an analysis of the optical rotation of these systems were made with the help of time-dependent density functional theory. The calculations highlight the contributions of the metal centers to the chiroptical properties. For 9a(1) and 9a(2), sigma-pi conjugation between the helicenes and the Pt-Pt moiety may contribute strongly to the optical rotation and electronic circular dichroism. PMID- 22052677 TI - Phenotypic assay of a hepatitis B virus strain carrying an rtS246T variant using a new strategy. AB - Phenotypic assays of hepatitis B virus (HBV) play an important role in research related to the problem of drug resistance that emerges during long-term nucleot(s)ide therapy in patients with chronic hepatitis B. Most of the phenotypic assay systems that are available currently rely on the transfection of recombinant replication-competent HBV DNA into hepatoma cell lines. Cloning clinical HBV isolates using conventional digestion-and-ligation techniques to generate replication-competent recombinants can be very difficult because of the sequence heterogeneity and unique structure of the HBV genome. In this study, a new strategy for constructing an HBV 1.1* recombinant was developed. The core of this strategy is the "fragment substitution reaction" (FSR). FSR allows PCR fragments to be cloned without digestion or ligation, providing a new tool for cloning fragments or genomes amplified from serum HBV DNA, and therefore making the assay of HBV phenotypes more convenient. Using this strategy, a phenotypic assay was performed on an HBV strain carrying an rtS246T variant isolated from a patient with chronic hepatitis B that was only responsive partially to entecavir therapy. The results indicated that this strain is sensitive to entecavir in vitro. PMID- 22052678 TI - CD304 is preferentially expressed on a subset of B-lineage acute lymphoblastic leukemia and represents a novel marker for minimal residual disease detection by flow cytometry. AB - Minimal residual disease (MRD) has emerged as a major prognostic factor for monitoring patients with B-lineage acute lymphoblastic leukemia (B-ALL). The quantification of MRD by flow cytometry (FC) is based on the identification of a leukemia-associated phenotype (LAP). Because phenotypic switch is common during treatment, multiple LAPs must be available and used for MRD detection over time. We evaluated the potential usefulness of CD304 as a new marker for monitoring MRD. CD304 was expressed in 48% of B-ALL (24/50) with discriminative fluorescence intensity compared with CD304-negative normal B-cell precursors (n = 15). The sensitivity of CD304-based MRD detection reached 10(-4), as with some of established LAPs. The stability of CD304 expression evaluated during therapy and at relapse confirms the usefulness of this marker for MRD quantification. Finally, CD304 was repeatedly expressed in patients with TEL-AML1 gene rearrangement, which warrants further investigation on its potential relevance as a prognosis marker or therapeutic target. PMID- 22052679 TI - Major congenital malformations in women with gestational diabetes mellitus: a systematic review and meta-analysis. AB - BACKGROUND: The risk of major congenital malformations (MCM) is increased in women with pregestational diabetes mellitus (PGDM). Whether this risk is increased in gestational diabetes mellitus (GDM) is still debated. The aim of this study was to perform a systematic review (and meta-analysis) of major congenital malformations in women with gestational diabetes versus a reference population. METHODS: We conducted a MEDLINE search (1 January 1995 to 31 December 2009) of original studies reporting data on major congenital malformations in women with gestational diabetes and a reference group. Information on pregestational diabetes was collected when available. Two investigators considered studies for inclusion and extracted data; discrepancies were solved by consensus. Meta-analysis tools were used to summarize results. MOOSE and PRISMA guidelines were followed. RESULTS: Two case control and 15 cohort studies were selected out of 3488 retrieved abstracts. A higher risk of major congenital malformations was observed in offspring of women with gestational diabetes with the following relative risk (RR)/odds ratios (OR) and 95% confidence intervals (CI): RR 1.16 (1.07-1.25) in cohort studies and OR 1.4 (1.22-1.62) in case control studies. Risk of major congenital malformations was much higher in offspring of women with PGDM than in those of the reference group: RR 2.66 (2.04 3.47) in cohort studies and OR 4.7 (3.01-6.95) in the single case control study providing information. CONCLUSION: There is a slightly higher risk of major congenital malformations in women with gestational diabetes than in the reference group. The contribution of women with overt hyperglycemia and other factors could not be ascertained. This risk, however, is much lower than in women with pregestational diabetes. PMID- 22052680 TI - Chiral hypervalent iodine reagents in asymmetric reactions. PMID- 22052681 TI - A novel mutation impairing the tertiary structure and stability of gammaC crystallin (CRYGC) leads to cataract formation in humans and zebrafish lens. AB - Congenital cataract is one of the leading causes of human blindness. In this study, we identified a novel, heterozygous c.385G=10 mIU/ml. Four subjects (two in each study) received an additional dose of monovalent hepatitis B vaccine and mounted anamnestic responses to vaccination. No vaccine-related serious adverse events were reported. This study confirms the long-term immunogenicity of the three-dose regimen of the combined hepatitis A and B vaccine, as eliciting long-term persistence of antibodies and immune memory against hepatitis A and B for up to at least 15 years after a primary vaccination. PMID- 22052691 TI - Not any new functional polymer can be for medicine: what about artificial biopolymers? AB - Man-made artificial organic polymers are among the more recent sources of materials used by humans. In medicine, they contribute to applications in surgery, dentistry and pharmacology. Nowadays, innovations in the field of therapeutic polymers rely on novel polymers for specific applications such as guided tissue regeneration, tissue engineering, drug delivery systems, gene transfection, etc. Introducing reactive chemical functions within or along polymer backbones is an attractive route to generate functional polymers for medicine. However, any candidate to effective application must fulfil a number of requirements, grouped under the terms biocompatibility and biofunctionality, to be of real interest and have a future for effective application. Whenever the application requires a therapeutic aid for a limited period of time to help natural healing, bioresorbability is to be taken into account on top of biocompatibility and biofunctionality. This contribution presents the case of "artificial biopolymers" and discusses the potential of some members of the family with respect to temporary therapeutic applications that require functional polymers. PMID- 22052692 TI - A male newborn with VACTERL association and Fanconi anemia with a FANCB deletion detected by array comparative genomic hybridization (aCGH). AB - We report on a male newborn with multiple congenital abnormalities consistent with the diagnosis of VACTERL association (vertebral, anal, cardiac, tracheo esophageal fistula, renal, and limb anomalies), who had Fanconi anemia (complementation group B) recognized by the detection of a deletion in chromosome Xp22.2 using an oligonucleotide array. The diagnosis of Fanconi anemia was confirmed by increased chromosomal breakage abnormalities observed in cultured cells that were treated with cross-linking agents. This is the first report in the literature of Fanconi anemia complementation group B detected by oligonucleotide array testing postnatally. PMID- 22052693 TI - Strong binding affinity of a zinc-porphyrin-based receptor for halides through the cooperative effects of quadruple C-H hydrogen bonds and axial ligation. AB - A new type of host compound (1), tetraphenyl zinc-porphyrin (ZnTPP) that contains four triazole groups at the ortho-position of each phenyl group, has been synthesized and characterized by using (1)H, (13)C NMR, and MALDI-TOF-MS analyses. The host-guest complex formation between 1 and halides was investigated by using (1)H NMR spectroscopy in [D(6)]DMSO. The triazole, benzyl, and phenylene proton signals were shifted upfield by the addition of halides in the form of tetrabutylammonium salts, which implies that the triazole protons in 1 are allocated very closely to the porphyrin ring and are directed toward the binding pocket over the porphyrin ring during the formation of hydrogen bonds. The UV/Vis absorption spectra showed that both the Soret and Q band absorptions of 1 underwent a strong redshift due to the addition of halides. Compound 1 exhibited surprisingly strong binding affinities for the halides, where the association constants for Cl(-), Br(-), and I(-) binding were estimated to be larger than 10(8), 1.79*10(7), and 1.84*10(5) M(-1), respectively. The UV/Vis absorption changes and the result of competitive titration using 4-tert-butylpyridine indicated that the cooperative effects of axial coordination and C-H...X hydrogen bond interactions resulted in the strong binding affinity of 1 to halides. PMID- 22052694 TI - Characterization of aerosols produced by cell sorters and evaluation of containment. AB - Despite the recognition of potential aerosol hazards associated with cell sorting by the flow cytometry community, there has been no previous study that has thoroughly characterized the aerosols that can be produced by cell sorters. In this study, an aerodynamic particle sizer was used to determine the concentration and aerodynamic diameter (AD) of aerosols produced by a FACS Aria II cell sorter under various conditions. Aerosol containment and evacuation were also evaluated using this novel methodology. The results showed that high concentrations of aerosols in the range of 1-3 MUm can be produced in fail mode and that with decreased sheath pressure, aerosol concentration decreased and AD increased. Although the engineering controls of the FACS Aria II for containment were effective, sort chamber evacuation of aerosols following a simulated nozzle obstruction was ineffective. However, simple modifications to the FACS Aria II are described that greatly improved sort chamber aerosol evacuation. The results of this study will facilitate the risk assessment of cell sorting potentially biohazardous samples by providing much needed data regarding aerosol production and containment. PMID- 22052695 TI - Facile fabrication of metallic nanostructures by tunable cracking and transfer printing. AB - You crack me up: A topographically patterned PDMS stamp was coated with thin metal film and swelled under organic vapor to induce the tunable cracking of the brittle film into metallic nanostructures (see SEM images, scale bars 1 MUm). UV/Vis spectra, OLED efficiency, and SERS spectra demonstrate the fine controllability of the metallic nanostructures, the well-ordered and highly regulable surface plasmons, and the facile fabrication process. PMID- 22052696 TI - Effect of solid content and composition of hydroxypropyl methylcellulose-lipid edible coatings on physico-chemical and nutritional quality of 'Oronules' mandarins. AB - BACKGROUND: Citrus fruit represent an important source of vitamin C, as well as other bioactive compounds. Edible coatings have the potential to extend shelf life of citrus by providing a semi-permeable barrier to water and gases, which depends on coating composition, solid content (SC), and cultivar. However, little is known about the effect of coatings on citrus nutritional quality. This work studies the effect of coating composition and SC of hydroxypropyl methylcellulose (HPMC)-beeswax (BW)-shellac coatings on the physico-chemical, sensory and nutritional quality of 'Oronules' mandarins. Coatings prepared at the same lipid content differed in the BW:shellac ratio (1:3 and 3:1) and SC of the formulations (40 and 80 g kg-1). RESULTS: The coating with 1:3 BW:shellac ratio and 80 g kg-1 SC was the most effective controlling weight loss, although it was less effective than the commercial wax tested. Increasing SC had a greater effect than the BW:shellac ratio in fruit internal atmosphere and sensory quality, with the presence of off-flavour when coatings were applied at 80 g kg-1 SC. Nutritional quality was not affected by the application of the different treatments. CONCLUSION: HPMC-lipid coatings have the potential to extend shelf life of 'Oronules' mandarins. However, care should be taken controlling formulation SC to avoid the build-up of off-flavour. PMID- 22052697 TI - Dedifferentiation-reprogrammed mesenchymal stem cells with improved therapeutic potential. AB - Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic ischemic brain damage rat model. Increased expression of bcl-2 family proteins and microRNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy. PMID- 22052698 TI - Health problems most commonly diagnosed among young female patients during visits to general practitioners and gynecologists in France before the initiation of the human papillomavirus vaccination program. AB - PURPOSE: Background rates for common health problems have seldom been estimated to facilitate interpretation of signals that may occur after a new public health intervention. Background rates of diagnoses from general practitioners (GPs) and gynecologists (GYNs) were assessed before the implementation of human papillomavirus (HPV) immunization program. METHODS: This cross-sectional study used data collected in 2006 in France. All visits of women (aged 11-23 years) to a GP or a GYN participating in the longitudinal patient data (LPD) network were considered. Diagnoses and symptoms were retrieved and classified according to the International Classification of Primary Care. Only diagnoses made in >= 1% of visits were reported in primary analyses. Independent analyses were performed for visits to GPs and GYNs and for adolescents and young adults. Finally, the rates of pre-specified health problems of interest (e.g., because of their potential identification as signals after HPV immunization) were computed from processed diagnostic data, using time windows consistent with HPV vaccination scheme. RESULTS: About 380,813 GP and 36,329 GYN visits were analyzed. Acute upper respiratory infections were the most frequently recorded diagnoses by GPs, accounting for 11,783 per 100,000 visits per year. Visits related to the respiratory system accounted for 10 of the 23 most frequent diagnoses by GPs. Genital candidiasis was the most frequent GYN diagnosis, accounting for 4746 per 100,000 visits per year. Most GYN visits were for pregnancy-related issues or menstrual problems. The main diagnoses were similar in adolescents compared with young adults in both GP and GYN settings. Pre-specified health problems occurred at high rates, as exemplified by acne that was diagnosed in 0.8% of patients during time windows consistent with HPV immunization. CONCLUSION: Diagnostic data processed from electronic health records identified the rates of common health events experienced by young female patients routinely visiting their GP or GYN before HPV immunization. Such rates may prove useful in interpreting adverse events reported after the launch of new medical interventions. PMID- 22052699 TI - Bioprocessing of bacteriophages via rapid drying onto microcrystals. AB - We present an alternative bioprocess for bacteriophages involving room temperature coprecipitation of an aqueous mixture of phage (Siphoviridae) and a crystallizable carrier (glutamine or glycine) in excess of water miscible organic solvent (isopropanol or isobutanol). The resultant suspension of phage-coated microcrystals can be harvested by filtration and the residual solvent removed rapidly by air-drying at a relative humidity of 75%. Albumin or trehalose added at 5% w/w of the crystalline carrier provide for better stabilization of the phage during co-precipitation. Free-flowing dry powders generated from an aqueous solution of phage (~13 log(10) pfu/mL) can be reconstituted in the same aqueous volume to a phage titer of almost 10 log(10) pfu/mL; high enough to permit subsequent formulation steps following bioprocessing. The phage-coated microcrystals remain partially stable at room temperature for at least one month, which compares favorably with phage immobilized into polyester microcarriers or lyophilized with excipient (1-5% polyethylene glycol 6000 or 0.1-0.5 M sucrose). We anticipate that this bioprocessing technique will have application to other phage families as required for the development of phage therapies. PMID- 22052700 TI - Relaxation-expansion model for self-driven retinal morphogenesis: a hypothesis from the perspective of biosystems dynamics at the multi-cellular level. AB - The generation of complex organ structures such as the eye requires the intricate orchestration of multiple cellular interactions. In this paper, early retinal development is discussed with respect to the structure formation of the optic cup. Although recent studies have elucidated molecular mechanisms of retinal differentiation, little is known about how the unique shape of the optic cup is determined. A recent report has demonstrated that optic-cup morphogenesis spontaneously occurs in three-dimensional stem-cell culture without external forces, indicating a latent intrinsic order to generate the structure. Based on this self-organizing phenomenon, we introduce the "relaxation-expansion" model to mechanically interpret the tissue dynamics that enable the spontaneous invagination of the neural retina. This model involves three consecutive local rules (relaxation, apical constriction, and expansion), and its computer simulation recapitulates the optic-cup morphogenesis in silico. PMID- 22052701 TI - Discrepant test findings in early infant diagnosis of HIV in a national reference laboratory in Kenya: challenges and opportunities for programs. AB - BACKGROUND: In Kenya, the availability of a cheap diagnostic service for HIV exposed infants has helped scale-up access to treatment, and provided a means by which programs that support Prevention of Mother to Child Transmission of HIV can be evaluated. As expected for any large testing program, discrepant and indeterminate results present a significant challenge. METHODS: Dried Blood Spots were collected from health centers countrywide and couriered to four laboratories for tests. Results were dispatched either by email, telephone, GSM SMS printer or courier. Between 2006 and 2009, tests were conducted with the Manual Roche v. 1.5 Assay. In 2010 the labs switched fully to the Cobas(r) AmpliPrep/ Cobas(r) TaqMan(r) HIV-1 Qual automated Roche Test. RESULTS: Between 2006 and 2010, the KEMRI CVR EID Lab conducted 64 591 HIV tests in on children <18 months of age. HIV tests (38 834) used the manual assay, while 17 133 tests used the automated assay. Overall, 10.7% (6915) of the samples tested positive, while 86.6% (55 967) tested negative. A total of 1.6% (1041) tested indeterminate and required a re bleed of the infant. Two hundred positive tests by the manual assay were retrieved randomly and retested using the automated assay. Among them, 192 (96%) remained positive, 5 (2.5%) were negative while 3 (1.5%) failed. A total of 160 negative samples by the manual assay were retrieved and retested with the automated assay. Among them, 154 (96.24%) remained negative, 3 (1.88%) tested positive while 3 (1.88%) failed. A total of 215 samples that gave indeterminate results by the manual assay were retested using the automated system. Among them, 62 (28.8%) gave positive results, 144 (66.97%) negative and 6 (2.8%) samples still gave discrepant results. Three (1.4%) did not amplify successfully. A few infants who were apparently positive appeared to test HIV negative with age. CONCLUSIONS: Indeterminate results are a significant challenge for HIV diagnostic services, as seen in the Kenyan EID Program. In our experience, they are more often negative than they are positive. False positive and false negative results can arise from clerical error, contamination and limitations of the technologies available. To forestall the consequences of such outcomes, the sensitivity and specificity of available assays must be further improved. All HIV positive samples should be retested for confirmation, and if confirmed, a new sample must be drawn and tested for DNA at the time the infant receives their initial results or starts antiretroviral therapy. Viral clearance is a phenomenon that requires further studies. PMID- 22052702 TI - A simple dose regimen of artesunate and amodiaquine based on arm span- or age range for childhood falciparum malaria: a preliminary evaluation. AB - A dose regimen of artesunate and amodiaquine based on arm span- or age range (DRAAAS), derived from a study of 1674 children, was compared with standard dose regimen of the same drugs calculated according to body weight (SDRAA) in 68 malarious children. Children on DRAAAS received 0.8-1.0 of artesunate/kg and 0.9 1.2 times amodiaquine/kg compared with those receiving SDRAA. Parasite and fever clearance and fall in hematocrit in the first 3 days were similar; both regimens were well tolerated. DRAAAS is simple and is efficacious. PMID- 22052703 TI - Can cormic index be a marker of pubertal onset and progress? PMID- 22052704 TI - Cortical parcellations of the macaque monkey analyzed on surface-based atlases. AB - Surface-based atlases provide a valuable way to analyze and visualize the functional organization of cerebral cortex. Surface-based registration (SBR) is a primary method for aligning individual hemispheres to a surface-based atlas. We used landmark-constrained SBR to register many published parcellation schemes to the macaque F99 surface-based atlas. This enables objective comparison of both similarities and differences across parcellations. Cortical areas in the macaque vary in surface area by more than 2 orders of magnitude. Based on a composite parcellation derived from 3 major sources, the total number of macaque neocortical and transitional cortical areas is estimated to be about 130-140 in each hemisphere. PMID- 22052705 TI - Adenovirus isolation rates in acute flaccid paralysis patients. AB - Adenoviruses usually cause asymptomatic or mild infection, but occasionally they produce various severe syndromes including neurological disorders. Association of adenovirus infection with acute flaccid paralysis has been investigated. Shedding of adenovirus with feces was detected in 1.05% of young children (mostly infants) with acute flaccid paralysis syndrome versus 0.42% in healthy contact children (P < 0.01). However, 85% of adenoviruses in the pediatric AFP patients belonged to HAdV-C species, which does not have a known neuropathogenic potential. Also, 40% of adenoviruses were isolated from patients with consequently established diagnosis of traumatic neuritis at the discharge, which was not compatible with virus ethology of neurological lesions. Higher adenovirus prevalence in young neurological patients could be affected by an underlying immune deficiency or by congestion in children's hospitals. Indeed, among 70 patients (40 infants, 30 adults) with primary immune deficiencies, asymptomatic shedding of adenoviruses was found in 10-17%; in one adult patient a mixture of HAdV-C2 and HAdV-D15 persisted for several months. Adenoviruses also could be detected in feces of 12% and 57% of healthy young children from two orphanages, respectively. A significant fraction of samples in these groups contained adenovirus mixtures. Therefore, immune deficiencies and congested groups in children's facilities (orphanages and hospitals) could affect significantly the prevalence of adenovirus shedding. The role of adenoviruses in AFP requires further study. PMID- 22052706 TI - Silk-based nanocomplexes with tumor-homing peptides for tumor-specific gene delivery. AB - Nanoscale complexes of recombinant silk molecules containing THPs with DNA are designed as less cytotoxic and highly target-specific gene carriers. Genetically engineered silk proteins containing poly(L-lysine) domains to interact with pDNA and the THP to bind to specific tumorigenic cells for target-specific pDNA delivery are prepared, followed by in vitro transfection into MDA-MB-435 melanoma cells, highly metastatic human breast tumor MDA-MB-231 cells, and non-tumorigenic MCF-10A breast epithelial cells. The silk/poly(L-lysine) block copolymer containing Lyp1 (ML-Lyp1) shows significant differences from silk/poly(L-lysine) block copolymer containing F3 (ML-F3) in cytotoxicity to MCF10A cells. ML-F3 is the most promising candidate for target delivery into tumorigenic cells. PMID- 22052707 TI - TP53 mutations and polymorphisms in primary myelofibrosis. AB - A total of 107 patients with chronic-phase primary myelofibrosis (PMF) were screened for TP53 mutations, which were detected in 4 (4%) cases: (i) E204E; GAG>GAA (silent exon 6); (ii) G245D; GGC>GAC (exon 7); (iii) R175H; CGC>CAC (exon 5); and (iv) six base insert (GGCGAG) after bp13767 (exon 6). Three (75%) of the four TP53-mutated cases also carried JAK2V617F whereas none were positive for MPL or IDH mutations. Two of the four TP53 mutated cases were also screened for TET2, ASXL1, DNMT3A, and EZH2 mutations and were negative. There was no significant difference in presenting features or survival between TP53 mutated and unmutated cases. TP53 exon 4 single nucleotide polymporphism (SNPs) data for codon 72 were available on 104 patients and included 56% with homozygous Arg72Arg, 33% with heterozygous Pro72Arg, and 11% with homozygous Pro72Pro. There were no significant differences among the three codon 72 genotypes in terms of presenting characteristics or survival. PMID- 22052708 TI - Crystal structures of Ziegler-Natta catalyst supports. AB - The crystal structures of three MgCl(2).nEtOH complexes with n=1.5, 2.8, and 3.3 have been fully determined. Such complexes are the fundamental precursors for Ziegler-Natta polymerization catalysts used to produce polyolefins on a multimillion-ton scale worldwide. The ab initio structure solution showed that the structure of MgCl(2).nEtOH complexes with n=1.5 and 2.8 are based on ribbons of metal-centered octahedra, whereas for n=3.3 this chainlike arrangement breaks into a threadlike structure of isolated octahedra linked by hydrogen bonds. A clear correlation between catalyst performance and the crystal structure of precursors has been found, and reveals the fundamental role of the latter in determining catalyst properties. The direct knowledge of building blocks in the precursor structures will help to develop more accurate models for activated catalysts. These models will not require the arbitrary and oversimplified assumption of locating the catalyst active sites on selected cut surfaces of the alpha-MgCl(2) crystal lattice. PMID- 22052709 TI - Efficient flexible phosphorescent polymer light-emitting diodes based on silver nanowire-polymer composite electrode. AB - Blue, green, and red electrophosphorescent polymer light-emitting diodes have been fabricated on silver nanowire-polymer composite electrode. The devices are 20%-50% more efficient than control devices on ITO/glass and exhibit small efficiency roll-off at high luminances. The blue PLEDs were repeatedly bent to 1.5 mm radius concave or convex with calculated strain in the emissive layer approximately 5% (tensile or compressive). PMID- 22052711 TI - Unprecedented catalytic hydrogenation of urea derivatives to amines and methanol. PMID- 22052712 TI - Combined partial trisomy 11q and partial monosomy 10p in a 19-year-old female patient: phenotypic and genotypic findings. AB - Constitutional partial trisomy 11q in man mostly occurs in combination with partial trisomy 22 due to a balanced parental translocation t(11;22). Occasionally a chromosome other than 22 is involved in the parental translocation with chromosome 11, resulting in partial monosomy for the other participating chromosome. We report of a patient with partial trisomy 11q and partial monosomy 10p [46,XX,der(10)t(10;11)(p15;q22)] due to a paternal balanced translocation [46,XY,t(10;11)(p15;q22)]. Array CGH showed heterozygosity for a deletion of ~3.46 Mb at 10p15.3p15.2 and gain of ~32.21 Mb at 11q22.2q25. The patient, a 19 year-old woman, has a multiple congenital anomaly syndrome with severe developmental and growth delay, muscular hypotonia, iris coloboma, abnormal external ears, widely spaced nipples, atrial septum defect, clubfoot, and arthrogryposis multiplex congenita. Despite multiple health problems and numerous hospitalizations due to massive seizures, pulmonary insufficiency and recurrent infections the patient reached adulthood. The clinical features in our patient are compared to other cases reported in the literature of either partial monosomy 10p or partial trisomy 11q. To the best of our knowledge, this is the first report of the combination of partial trisomy 11q and partial monosomy 10p. Comparing the molecular karyotype and the phenotype of our patient to other patients, the clinical features of our patient are more likely due to partial trisomy 11q than to partial monosomy 10p. PMID- 22052713 TI - Two-stage method to remove population- and individual-level outliers from longitudinal data in a primary care database. AB - PURPOSE: In the UK, primary care databases include repeated measurements of health indicators at the individual level. As these databases encompass a large population, some individuals have extreme values, but some values may also be recorded incorrectly. The challenge for researchers is to distinguish between records that are due to incorrect recording and those which represent true but extreme values. This study evaluated different methods to identify outliers. METHODS: Ten percent of practices were selected at random to evaluate the recording of 513,367 height measurements. Population-level outliers were identified using boundaries defined using Health Survey for England data. Individual-level outliers were identified by fitting a random-effects model with subject-specific slopes for height measurements adjusted for age and sex. Any height measurements with a patient-level standardised residual more extreme than +/-10 were identified as an outlier and excluded. The model was subsequently refitted twice after removing outliers at each stage. This method was compared with existing methods of removing outliers. RESULTS: Most outliers were identified at the population level using the boundaries defined using Health Survey for England (1550 of 1643). Once these were removed from the database, fitting the random-effects model to the remaining data successfully identified only 75 further outliers. This method was more efficient at identifying true outliers compared with existing methods. CONCLUSIONS: We propose a new, two-stage approach in identifying outliers in longitudinal data and show that it can successfully identify outliers at both population and individual level. Copyright (c) 2011 John Wiley & Sons, Ltd. PMID- 22052714 TI - Fibre-rich additives--the effect on staling and their function in free-standing and pan-baked bread. AB - BACKGROUND: The use of dietary fibre in bread products is increasing because of consumer demand for healthier products. However, an increase in dietary fibre level changes the rheological properties of the dough and also the quality properties of the final bread product. In this study, effects on dough and bread staling were followed after replacing 3% of wheat flour by fibre-rich additives (fine durum, oat bran, rye bran and wheat bran). Free-standing and pan-baked loaves were baked to compare the influence of baking method and loaf shape. RESULTS: All additives increased dough stability, with oat bran giving the greatest stability and longest development time. Parameters measured during storage were distribution, migration and loss of water, cutability, crumbliness, firmness and springiness. Furthermore, amylopectin retrogradation and amylase lipid complex formation were assessed. Oat bran provided similar or better results than the control for all staling parameters, while other additives gave no general improvements. Cutability reached a plateau when crumb firmness was >= 4 N. CONCLUSION: Small amounts of fibre-rich additives had a significant influence on staling. However, the baking method (free-standing or pan-baked bread) had a greater impact on staling than the additives, thus displaying the importance of the baking method. Cutability was found to be related to firmness. PMID- 22052715 TI - A sensitive method for determination of furanodiene in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study. AB - Furanodiene, a sesquiterpene component extracted from the essential oil of the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling (Wen Ezhu), is widely used in traditional Chinese medicine. A sensitive analytical method was established and validated for furanodiene in rat plasma, which was further applied to assess the pharmacokinetics of furanodiene in rats receiving a single dose of furanodiene. Liquid chromatography tandem mass spectrometry (LC/MS/MS) in multiple reaction monitoring mode was used in the method and costundide was used as internal standard. A simple protein precipitation based on methanol was employed. The simple sample cleanup increased the throughput of the method substantially. The method was validated over the range of 1-1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1 ng/mL for furanodiene in plasma. Intra- and inter-day accuracies for furanodiene were 88-115 and 102 107%, and the inter-day precision less than 14.4%. After a single oral dose of 10 mg/kg of furanodiene, the mean peak plasma concentration of furanodiene was 66.9 +/- 23.4 ng/mL at 1 h, the area under the plasma concentration-time curve (AUC(0 10 h)) was 220 +/- 47.8 h ng/mL, and the elimination half-life was 1.53 +/- 0.06 h. After an intravenous adminstration of furanodiene at a dosage of 5 mg/kg, the area under the plasma concentration-time curve was 225 +/- 76.1 h?ng/mL, and the elimination half-life was 2.40 +/- 1.18 h. Based on this result, the oral bioavailability of furanodiene in rats at 10 mg/kg is 49.0%. PMID- 22052716 TI - Musculoskeletal morphology and regionalization within the dorsal and anal fins of bluegill sunfish (Lepomis macrochirus). AB - Ray-finned fishes actively control the shape and orientation of their fins to either generate or resist hydrodynamic forces. Because of the emergent mechanical properties of their segmented, bilaminar fin rays (lepidotrichia), and actuation by multiple muscles, fish can control the rigidity and curvature of individual rays independently, thereby varying the resultant forces across the fin surfaces. Expecting that differences in fin-ray morphology should reflect variation in their mechanical properties, we measured several musculoskeletal features of individual spines and rays of the dorsal and anal fins of bluegill sunfish, Lepomis macrochirus, and assessed their mobility and flexibility. We separated the fin-rays into four groups based on the fin (dorsal or anal) or fin-ray type (spine or ray) and measured the length of the spines/rays and the mass of the three median fin-ray muscles: the inclinators, erectors and depressors. Within the two ray groups, we measured the portion of the rays that were segmented vs. unsegmented and branched vs. unbranched. For the majority of variables tested, we found that variations between fin-rays within each group were significantly related to position within the fin and these patterns were conserved between the dorsal and anal rays. Based on positional variations in fin-ray and muscle parameters, we suggest that anterior and posterior regions of each fin perform different functions when interacting with the surrounding fluid. Specifically, we suggest that the stiffer anterior rays of the soft dorsal and anal fins maintain stability and keep the flow across the fins steady. The posterior rays, which are more flexible with a greater range of motion, fine-tune their stiffness and orientation, directing the resultant flow to generate lateral and some thrust forces, thus acting as an accessory caudal fin. PMID- 22052717 TI - Oxidation of Zn(Cys)4 zinc finger peptides by O2 and H2O2: products, mechanism and kinetics. AB - The reactivity of a series of Zn(Cys)(4) zinc finger model peptides towards H(2)O(2) and O(2) has been investigated. The oxidation products were identified by HPLC and ESI-MS analysis. At pH<7.5, the zinc complexes and the free peptides are oxidised to bis-disulfide-containing peptides. Above pH 7.5, the oxidation of the zinc complexes by H(2)O(2) also yields sulfinate- and sulfonate-containing overoxidised peptides. At pH 7.0, monitoring of the reactions between the zinc complexes and H(2)O(2) by HPLC revealed the sequential formation of two disulfides. Several techniques for the determination of the rate constant for the first oxidation step corresponding to the attack of H(2)O(2) by the Zn(Cys)(4) site have been compared. This rate constant can be reliably determined by monitoring the oxidation by HPLC, fluorescence, circular dichroism or absorption spectroscopy in the presence of excess ethyleneglycol bis(2-aminoethyl ether)tetraacetic acid. In contrast, monitoring of the release of zinc with 4-(2 pyridylazo)resorcinol or of the thiol content with 5,5'-dithiobis(2 nitrobenzoate) did not yield reliable values of this rate constant for the case in which the formation of the second disulfide is slower than the formation of the first. The kinetic measurements clearly evidence a protective effect of zinc on the oxidation of the cysteines by both H(2)O(2) and O(2), which points to the fact that zinc binding diminishes the nucleophilicity of the thiolates. In addition, the reaction between the zinc finger and H(2)O(2) is too slow to consider zinc fingers as potential sensors for H(2)O(2) in cells. PMID- 22052718 TI - Acute changes in the embryonic heart rate: a response to environmental challenges? PMID- 22052719 TI - Biodegradable polymers derived from amino acids. AB - In the past three decades, the use of polymeric materials has increased dramatically for biomedical applications. Many alpha-amino acids derived biodegradable polymers have also been intensely developed with the main goal to obtain bio-mimicking functional biomaterials. Polymers derived from alpha-amino acids may offer many advantages, as these polymers: (a) can be modified further to introduce new functions such as imaging, molecular targeting and drugs can be conjugated chemically to these polymers, (b) can improve on better biological properties like cell migration, adhesion and biodegradability, (c) can improve on mechanical and thermal properties and (d) their degradation products are expected to be non-toxic and readily metabolized/excreted from the body. This manuscript focuses on biodegradable polymers derived from natural amino acids, their synthesis, biocompatibility and biomedical applications. It is observed that polymers derived from alpha-amino acids constitute a promising family of biodegradable materials. These provide innovative multifunctional polymers possessing amino acid side groups with biological activity and with innumerous potential applications. PMID- 22052720 TI - Selection for resistance, reversion towards susceptibility and synergism of chlorantraniliprole and spinetoram in obliquebanded leafroller, Choristoneura rosaceana (Lepidoptera: Tortricidae). AB - BACKGROUND: Obliquebanded leafroller, Choristoneura rosaceana (Harris), is an economic pest of pome fruits throughout North America. Repeated applications of broad-spectrum insecticides have resulted in the development of resistance, cross resistance and multiple resistance in this pest. Studies were conducted to determine the possibility of resistance evolution, stability of resistance and the effect of metabolic synergists on toxicity of new reduced-risk insecticides chlorantraniliprole and spinetoram in C. rosaceana. RESULTS: Larvae of C. rosaceana were selected for resistance to chlorantraniliprole and spinetoram in the laboratory. Significant levels of resistance to each insecticide were observed after 12 generations of selection. In the absence of selection pressure, susceptibility of a subset of larvae from both chlorantraniliprole- and spinetoram-selected populations reverted to preselection levels after five and six generations respectively, indicating that resistance to both chlorantraniliprole and spinetoram was unstable in C. rosaceana. In synergist bioassays performed after 12 generations of selection, S,S,S-tributylphosphoro trithioate (DEF) and piperonyl butoxide (PBO) synergized the toxicity of chlorantraniliprole and spinetoram respectively, suggesting the involvement of esterases in chlorantraniliprole resistance and the involvement of mixed-function oxidases in spinetoram resistance. CONCLUSION: These findings suggest that chlorantraniliprole and spinetoram could be incorporated into C. rosaceana resistance management programs by using rotational strategies. PMID- 22052721 TI - Chemiresistive sensing with chemically modified metal and alloy nanoparticles. AB - This review describes the use of chemically modified pure and alloyed metal nanoparticles for chemiresistive sensing applications. Chemically modified metal nanoparticles consist of a pure or alloyed metallic core with some type of chemical coating. Researchers have studied the electronic properties of 1D, 2D, and 3D assemblies of chemically modified metal nanoparticles, and even single individual nanoparticles. The interaction with the analyte alters the conductivity of the sensitive material, providing a signal to measure the analyte concentration. This review focuses on chemiresistive sensing of a wide variety of gas- and liquid-phase analytes with metal nanoparticles coated with organothiols, ions, polymers, surfactants, and biomolecules. Different strategies used to incorporate chemically modified nanoparticles into chemiresistive sensing devices are reviewed, focusing on the different types of metal and alloy compositions, coatings, methods of assembly, and analytes (vapors, gases, liquids, biological materials), along with other important factors. PMID- 22052722 TI - Structural magnetic resonance imaging in eating disorders: a systematic review of voxel-based morphometry studies. AB - This systematic review summarises and critically appraises the literature on structural magnetic resonance imaging in people with a current or past eating disorder. Studies using voxel-based morphometry image analysis were included. Ten studies reported on a total of 236 people with a current or past eating disorder and 257 healthy controls. Sample heterogeneity prohibited a meta-analytic approach. The findings do not unequivocally indicate grey or white matter volume abnormalities in people with an eating disorder. Nevertheless, these preliminary data suggest that, compared with healthy controls, people with anorexia nervosa have decreased grey matter in a range of brain regions and that those with bulimia nervosa have increased grey matter volumes in frontal and ventral striatal areas. Research in the recovery phase and longitudinal studies suggest that potential brain tissue abnormalities may recover with clinical improvement. Overall, as the available data are inconclusive, further efforts in this field are warranted. PMID- 22052723 TI - Genetic and clinical profiles of spondylocostal dysostosis patients in Taiwan. PMID- 22052724 TI - Asymmetric magnetization reversal of stripe-patterned exchange bias layer systems for controlled magnetic particle transport. AB - Domain wall movement assisted transport of particles: exchange-biased samples with designed stripe-domains show strong stray fields and an asymmetric magnetization reversal. Using these characteristics superparamagnetic particles can be trapped and transported directly on the sample over large-scale areas. High particle velocities, small external fields, and automatically reduced particle clustering allow broad applicability of this transport method. PMID- 22052725 TI - Dynamic substrate enhancement for the identification of specific, second-site binding fragments targeting a set of protein tyrosine phosphatases. AB - Protein tyrosine phosphatases (PTPs) are key regulators in living systems and thus are attractive drug targets. The development of potent, selective PTP inhibitors has been a difficult challenge mainly due to the high homology of the phosphotyrosine substrate pockets. Here, a strategy of dynamic substrate enhancement is described targeting the secondary binding sites of PTPs. By screening four different PTPs from bacterial (MptpA) and human origin (PTP1B, HePtp, Shp2) with this assay, specific fragments were identified. One highly specific fragment that binds to the secondary site of Mycobacterium tuberculosis protein tyrosine phosphatase A (MptpA) was characterized in order to validate the assay concept. Finally by covalently linking the secondary fragment to a phosphotyrosine mimetic, a moderately active but highly specific inhibitor of MptpA was obtained. PMID- 22052726 TI - Development and validation of an LC-MS/MS-ESI method for the determination of lorglumide, a CCK-1 antagonist in mouse plasma: application to a pharmacokinetic study. AB - A highly sensitive, rapid assay method was developed and validated for the estimation of lorglumide in mouse plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in positive-ion mode. The assay procedure involves extraction of lorglumide and phenacetin (internal standard, IS) from mouse plasma with simple protein precipitation. Chromatographic separation was achieved using an isocratic mobile (0.2% formic acid solution-acetonitrile, 20:80, v/v) at a flow-rate of 0.5 mL/min on an Atlantis dC18 column maintained at 40 degrees C with a total run time of 4.0 min. The MS/MS ion transitions monitored were 459.2 -> 158.4 for lorglumide and 180.1 -> 110.1 for IS. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.42 ng/mL and the linearity range extended from 0.42 to 500 ng/mL. The intra and inter-day precisions were in the ranges of 1.47-10.9 and 3.56-7.53, respectively. PMID- 22052727 TI - Effects of specific egg yolk antibody (IgY) on the quality and shelf life of refrigerated Paralichthys olivaceus. AB - BACKGROUND: The spoilage of fishery food has been attributed to limited types of microorganisms called specific spoilage organisms (SSO). Unlike traditional food preserving techniques which usually exploit broad-spectrum antimicrobial agents, here, based on the specific antimicrobial activity of egg yolk antibodies (IgY) against two SSO in refrigerated fish (Shewanella putrefaciens and Pseudomonas fluorescens), a novel strategy for fish preservation was suggested and evaluated. RESULTS: During storage of Paralichthys olivaceus fillets at 4 +/- 1 degrees C, the bacteria growth (including total microorganisms and the two SSO) in test groups was significantly inhibited in comparison to that of controls (P < 0.05). This antibacterial activity of the specific IgY was also confirmed by chemical analysis (pH, total volatile base nitrogen and 2-thiobarbituric acid value) and sensory evaluation, and the shelf life of samples was extended approximately from 9 days to 12-15 days in the presence of the specific IgY. CONCLUSION: These results indicated a significant antimicrobial activity of the anti-SSO IgY for refrigerated fish products, which allowed us to suggest its potential as a bio preservative for seafood. PMID- 22052728 TI - Electrocorticographic control of a prosthetic arm in paralyzed patients. AB - OBJECTIVE: Paralyzed patients may benefit from restoration of movement afforded by prosthetics controlled by electrocorticography (ECoG). Although ECoG shows promising results in human volunteers, it is unclear whether ECoG signals recorded from chronically paralyzed patients provide sufficient motor information, and if they do, whether they can be applied to control a prosthetic. METHODS: We recorded ECoG signals from sensorimotor cortices of 12 patients while they executed or attempted to execute 3 to 5 simple hand and elbow movements. Sensorimotor function was severely impaired in 3 patients due to peripheral nervous system lesion or amputation, moderately impaired due to central nervous system lesions sparing the cortex in 4 patients, and normal in 5 patients. Time frequency and decoding analyses were performed with the patients' ECoG signals. RESULTS: In all patients, the high gamma power (80-150 Hz) of the ECoG signals during movements was clearly responsive to movement types and provided the best information for classifying different movement types. The classification performance was significantly better than chance in all patients, although differences between ECoG power modulations during different movement types were significantly less in patients with severely impaired motor function. In the impaired patients, cortical representations tended to overlap each other. Finally, using the classification method in real time, a moderately impaired patient and 3 nonparalyzed patients successfully controlled a prosthetic arm. INTERPRETATION: ECoG signals appear useful for prosthetic arm control and may provide clinically feasible motor restoration for patients with paralysis but no injury of the sensorimotor cortex. PMID- 22052729 TI - Nonvisualization of fetal gallbladder increases the risk of cystic fibrosis. AB - OBJECTIVE: The aim of our study is to evaluate the prevalence of cystic fibrosis (CF) in fetuses referred for genetic testing because of ultrasonographic sign (nonvisualized fetal gallbladder--NVFGB). METHOD: We reviewed the results of CFTR gene analysis over the period 2002 to 2009 in all consecutive cases referred because of NVFGB in Western France. We correlated these data with the presence of a more classical ultrasonographic finding (fetal echogenic bowel - FEB). RESULTS: Cystic fibrosis was diagnosed in 5 of the 37 fetuses with NVFGB (13.5%, 95% confidence interval (CI): [2.5%; 24.5%]) and in only 9 of the 229 other cases referred because of FEB (3.9%, 95% CI: [3.2%; 14.7%]). In our series, all CF affected fetuses with NVFGB also had FEB. The risk of CF was 11.6-fold higher in fetuses with both indications (NVFGB + FEB) than in fetuses with isolated FEB (45.5% vs 3.9%, RR = 11.6, 95% CI: [4.7%; 28.8%], p = 0.0001). We also estimated that the residual risk of CF was less than 1 in 68 (1.5%) when a single mutation was identified in the fetus by our molecular protocol. CONCLUSION: Ultrasonographic evidence of NVFGB is an additional risk factor for CF in cases with FEB. PMID- 22052730 TI - Research decisions in the face of heterogeneity: what can a new study tell us? AB - Willan and Eckermann describe a method for dealing with heterogeneity in value of information (VOI) calculations for prioritising and designing new research. Their article raises three fundamental (inter-related) issues for VOI methods: (1) how to make sense of the concept of uncertainty in a cost-effectiveness analysis (CEA) model, (2) the interpretation of heterogeneity in CEA, and (3) the relationship between data from a new study and the CEA model when there is heterogeneity. We discuss these three issues using an illustrative example meta analysis of magnesium for myocardial infarction. Careful consideration of the relationship between existing (and future) evidence and the CEA model is required to provide practical VOI methods that can help research funders prioritise new research in the face of heterogeneity. PMID- 22052732 TI - High-grade primary leiomyosarcoma in the mandible: diagnosis and treatment. AB - BACKGROUND: Leiomyosarcoma is a malignant tumor that originates in smooth muscle cells and is rarely found in the oral cavity. We present a case of high-grade primary leiomyosarcoma in the mandible and discuss the diagnosis process. METHODS: The patient was a 64-year-old white man who had a slight increase in volume in the left-side mandible with a radiolucent osteolytic image with the destruction of the mandibular cortex. Incisional biopsy and preoperative examination were performed, including cone beam CT and examination by immunohistochemistry that defined the histologic diagnosis of leiomyosarcoma. The patient underwent reconstruction with an osteocutaneous flap with microvascular anastomosis. RESULTS: Two years after the surgery, there was no sign of recurrence of the lesion. CONCLUSION: The use of cone beam CT to define the limits of the lesion and the immunohistochemical findings were essential to establish the treatment plan. PMID- 22052733 TI - Shell mycosis in a group of Hermann's tortoises (Testudo hermanni). PMID- 22052734 TI - Acute phase proteins in three healthy antelope species. PMID- 22052735 TI - Ionic liquids containing the triply negatively charged tricyanomelaminate anion and a B(C6F5)3 adduct anion. AB - Room-temperature ionic liquids containing the triply charged tricyanomelaminate (tcmel) ion [C(3)N(6)(CN)(3)](3-) were synthesized. The 1-methyl-3 methylimidazolium (MMIm), 1-ethyl-3-methylimidazolium (EMIm), and 1-butyl-3 methylimidazolium (BMIm) salts of the tricyanomelaminate ion have glass transition temperatures (-6, -20, and -30 degrees C) similar to those found for the analogous monomeric dicyanoamide salts. They are thermally stable up to over 200 degrees C and dissolve in polar organic solvents. Addition of B(C(6)F(5))(3) to M(3) [tcmel] (M=Na, MMIm, EMIm, BMIm) yields salts containing the very voluminous adduct ion [C(3)N(6) {CN.B(C(6)F(5))(3)}(3)](3-) (tcmel_3B). The solid state structure of [MMIm](3-) [tcmel] shows only long cation...anion contacts but in large number, while the solid-state structure of [Na(THF)(3)](3-) [tcmel_3B].1.76 THF displays strong interactions of the sodium cation with the amido nitrogen atoms of the anion. Hence this adduct anion cannot be regarded as a weakly coordinating anion. A similar situation is found for the MMIm salt, [MMIm](3) [tcmel_3B].2.66 CH(2)Cl(2), in which weak hydrogen bonds with the acidic proton of the MMIm ion are observed. On the basis of computations the energetics, structural trends, and charge transfer of adduct anion formation were studied. PMID- 22052736 TI - Identifying the presence of neonicotinoidresistant peach-potato aphid (Myzus persicae) in the peach-growing regions of southern France and northern Spain. AB - BACKGROUND: The neonicotinoid class of insecticides is a key component of pest management strategies used by stone fruit producers in Europe. Neonicotinoids are currently one of the most important tools for control of the peach-potato aphid (Myzus persicae). Overreliance on neonicotinoids has led to the development of resistance through a combination of metabolic and target-site resistance mechanisms in individual aphids. A resistance monitoring project was conducted by Syngenta in 2010 to determine the resistance status of M. persicae populations collected from France and Spain, and to determine the frequency of the target site mutation in those populations. RESULTS: Resistance monitoring suggests that resistance to neonicotinoids is relatively widespread in populations of M. persicae collected from peach orchards in the Languedoc-Roussillon, Provence Alpes-Cote d'Azur and Rhone-Alpes regions of France, and resistance can be associated with the frequency of the target-site mutation (R81T). The R81T mutation in its heterozygous form is also present in Spanish populations and is associated with neonicotinoid resistance. CONCLUSION: The widespread nature of neonicotinoid resistance in southern France and the potential for resistance development in northern Spain highlight the need for a coordinated management strategy employing insecticides with different modes of action to reduce the selection pressure with neonicotinoids. PMID- 22052737 TI - Biotemplated magnetic nanoparticle arrays. AB - Immobilized biomineralizing protein Mms6 templates the formation of uniform magnetite nanoparticles in situ when selectively patterned onto a surface. Magnetic force microscopy shows that the stable magnetite particles maintain their magnetic orientation at room temperature, and may be exchange coupled. This precision-mixed biomimetic/soft-lithography methodology offers great potential for the future of nanodevice fabrication. PMID- 22052738 TI - Enhancement of the inhibitory effect of an IL-15 antagonist peptide by alanine scanning. AB - IL-15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL-15 antagonist peptide corresponding to sequence 36-45 of IL-15 (KVTAMKCFLL) named P8, which specifically binds to IL-15Ralpha and inhibits IL-15 biological activity with a half maximal inhibitory concentration (IC50) of 130 u m in CTLL-2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL-15Ralpha, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL-15Ralpha. We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non-charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24 um. We also found that this peptide was more active than peptide P8 in the inhibition of TNFalpha secretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL-15 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis. PMID- 22052739 TI - Two new cases with microdeletion of 17q23.2 suggest presence of a candidate gene for sensorineural hearing loss within this region. AB - Microdeletion of the 17q23.2 region has very recently been suggested as a new emerging syndrome based on the finding of 8 cases with common phenotypes including mild-to-moderate developmental delay, heart defects, microcephaly, postnatal growth retardation, and hand, foot, and limb abnormalities. In this report, we describe two new 17q23.2 deletion patients with mild intellectual disability and sensorineural hearing loss. They both had submicroscopic deletions smaller than the common deleted region for the 8 previously described 17q23.2 microdeletion cases. TBX4 was previously suggested as the responsible gene for the heart or limb defects observed in 17q23.2 deletion patients, but the present cases do not have these features despite deletion of this gene. The finding of sensorineural hearing loss in 5 of the 10 cases, including the present cases, with a microdeletion at17q23.2, strongly suggests the presence of a candidate gene for hearing loss within this region. We screened 41 patients with profound sensorineural hearing loss for mutations of TBX2 and detected no mutations. PMID- 22052740 TI - Sulfur-impregnated activated carbon fiber cloth as a binder-free cathode for rechargeable Li-S batteries. AB - A route for the preparation of binder-free sulfur-carbon cathodes is developed for lithium sulfur batteries. The method is based on the impregnation of elemental sulfur into the micropores of activated carbon fibers. These electrodes demonstrate good electrochemical performance at high current density attributed to the uniform dispersion of sulfur inside the carbon fiber. PMID- 22052741 TI - Generation of a mono-ubiquitinated PCNA mimic by click chemistry. AB - Genotoxic stress results in more than 50 000 damaged DNA sites per cell per day. During DNA replication, processive high-fidelity DNA polymerases generally stall at DNA lesions and have to be displaced by translesion synthesis DNA polymerases, which are able to bypass the lesion. This switch is mediated by mono ubiquitination of the processivity factor proliferating cell nuclear antigen (PCNA). To further investigate the regulation of the DNA polymerase exchange, we developed an easy and efficient method to synthesize site-specifically mono ubiquitinated PCNA by click chemistry. By incorporating artificial amino acids that carry an azide (Aha) or an alkyne (Plk) in their side chains, into ubiquitin (Ub) and PCNA, respectively, we were able to link the two proteins site specifically by the Cu(I) -catalyzed azide-alkyne cycloaddition. Finally, we show that the synthetic PCNA-Ub is able to stimulate DNA synthesis by DNA polymerase delta, and that DNA polymerase eta has a higher affinity for PCNA-Ub than to PCNA. PMID- 22052742 TI - Blood values of adult captive cheetahs (Acinonyx jubatus) fed either supplemented beef or whole rabbit carcasses. AB - This study evaluated nutrient intake and relevant blood parameters of 14 captive cheetahs, randomly assigned to a meat-only diet (supplemented beef, SB) or a whole prey diet (whole rabbit, WR) for 4 weeks each. Despite a higher food intake, daily metabolizable energy intake was lower when fed WR (308 kJ BW(-1) ) compared with SB (347 kJ BW(-1) ) (P = 0.002). The ratio of protein to fat was markedly lower for WR (2.3:1) compared with SB (8.8:1), which was reflected in higher serum urea levels when fed SB (P = 0.033), and a tendency for elevated cholesterol levels when fed WR (P = 0.055). Taurine intake of cheetahs fed WR was low (0.06% on DM basis); however, analytical error during taurine analysis cannot be ruled out. Feeding WR resulted in a well-balanced mineral intake, in contrast to SB. The latter provided a low calcium:phosphorus ratio (1:2.3), thereby increasing the risk of metabolic bone disease. The high zinc content of SB (200 mg/kg DM), compared with WR (94 mg/kg DM), was reflected in higher serum zinc concentrations (P = 0.011). Feeding WR resulted in an increase in serum vitamin A (P = 0.011). Therefore, the risk of hypervitaminosis A in captive cheetahs when fed WR exclusively on a long-term basis should be evaluated. Our findings suggest that neither diet is likely to provide appropriate nutrition to captive cheetahs when fed exclusively. PMID- 22052743 TI - Quantitative determination of tiopronin in human plasma by LC-MS/MS without derivatization. AB - Tiopronin (TP) is a synthetic thiol compound without chromophore. By optimizing the chromatographic conditions and sample preparation processes, an improved LC MS/MS analytical method without derivatization has been developed and validated to determine TP concentrations in human plasma. After reduction with 1,4 dithiothreitol, plasma samples were deproteinized with 10% perchloric acid. The post-treatment samples were analyzed on a C8 column interfaced with a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode. Methanol-5 mmol/L ammonium acetate (20:80, v/v) was used as the isocratic mobile phase. The assay was linear over the concentration range of 40.0-5000 ng/mL. The intra- and inter-day precisions were within 12.9% in terms of relative standard deviation and the accuracy within 5.6% in terms of relative error. This simple and sensitive LC-MS/MS method with short analytical time (3.5 min each sample) was successfully applied to the pharmacokinetic study of TP in healthy Chinese male volunteers after an oral dose of 300 mg TP. PMID- 22052744 TI - Characterization and prediction by near-infrared reflectance of mineral composition of rocket (Eruca vesicaria subsp. sativa and Eruca vesicaria subsp. vesicaria). AB - BACKGROUND: Minerals are essential for human nutrition and must be obtained from our diet. Crucifer vegetables are a good source of these nutrients. Our objectives were to determine the genetic variability for mineral content and to evaluate the use of near-infrared reflectance spectroscopy (NIRS) for prediction of ashes and minerals among and within the rocket species Eruca vesicaria subsp. sativa and vesicaria. The minerals studied were iron (Fe), copper (Cu), sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), manganese (Mn) and zinc (Zn). RESULTS: The maximum mean values obtained for all the accessions (mean +/- SE) were 235.5 +/- 1.5 mg ashes kg(-1), 273.3 +/- 4.2 mg Fe kg(-1), 18.1 +/- 0.4 mg Cu kg(-1), 2.8 +/- 0.1 g Na kg(-1), 71.6 +/- 1.0 g K kg(-1), 64.6 +/- 1.2 g Ca kg(-1), 6.8 +/- 0.1 g mg kg(-1), 101.6 +/- 1.2 mg Mn kg(-1), and 67.1 +/- 0.4 mg Zn kg(-1) of dry weight. CONCLUSION: The statistical analysis showed significant differences for all the minerals, except Ca, for each accession studied individually and for accessions grouped within countries. The results indicate that NIRS can be used as a rapid screening method for determining total mineral, Fe, Na, K, and Zn in rocket. PMID- 22052745 TI - A longer tracheal occlusion period results in increased lung growth in the nitrofen rat model. AB - OBJECTIVE: Prenatal tracheal occlusion (TO) promotes lung growth and is applied clinically in fetuses with severe congenital diaphragmatic hernia. Limited data are available regarding the effect of duration of TO on lung development. Our objective was to evaluate the effects of long (2 and 2.5 days) versus short (1 day) TO on lung development in rats with nitrofen-induced diaphragmatic hernia. METHOD: Nitrofen was administered on embryonic day (ED) 9 and fetal TO performed either on ED18.5, 19 or 20 (term = 22 days). Sham-operated and untouched littermates served as controls. On ED21, lungs were harvested and only fetuses with a left-sided diaphragmatic defect were included in further analyses. RESULTS: Lung-body-weight ratio incrementally increased with the duration of TO. Increased proliferation following long TO was confirmed by immunohistochemistry and qRT-PCR for the proliferation marker Ki-67. Irrespective of duration, TO induced more complex airway architecture. Medial wall thickness of pulmonary arteries was thinner after long rather than short TO. CONCLUSION: In the nitrofen rat model of congenital diaphragmatic hernia, a longer period of TO leads to enhanced lung growth and less muscularized pulmonary arteries. PMID- 22052746 TI - The contribution of general and cancer-related variables in explaining physical activity in a breast cancer population 3 weeks to 6 months post-treatment. AB - OBJECTIVE: Physical activity determinants are subject to change when confronted with the diagnosis of 'cancer' and new cancer-related determinants appear. The aim of the present study is to compare the contribution of cancer-related determinants with more general ones in explaining physical activity 3 weeks to 6 months post-treatment. METHODS: A theory-based and validated questionnaire was used to identify physical activity levels (total and domain-specific) and associated determinants among 464 breast cancer survivors (aged 18 to 65 years) 3 weeks to 6 months post-treatment. RESULTS: Descriptive analyses showed higher scores for general determinants in comparison with cancer-related determinants. Nevertheless, regression analyses showed that both general and cancer-related determinants explained total and domain-specific physical activity. Self efficacy, enjoyment, social support, lack of time and lack of company were important general determinants. The perception of returning to normal life, cancer-related barriers (fatigue, lack of energy and physical side effects) and self-efficacy in overcoming these barriers were important cancer-related determinants. Although results differed according to the women's working status and the physical activity domain, general self-efficacy explained most physical activity types in both groups. CONCLUSION: Comparable with the general population, enhancing breast cancer survivors' self-efficacy in being sufficiently physically active seems to be important in physical activity interventions post-treatment. However, interventions should be tailored to the experienced symptoms and working status of the women. PMID- 22052747 TI - Activity profile sequences: a concept to account for the progression of compound activity in target space and to extract SAR information from analogue series with multiple target annotations. PMID- 22052748 TI - Use of endoscopy with narrow-band imaging system in evaluating oral leukoplakia. AB - BACKGROUND: The purpose of this study was to analyze the relationship between clinical features of oral leukoplakia using endoscopy with broadband white light, narrow-band imaging (NBI) illumination, and histopathology, and to discuss the clinical relevance of the NBI system. METHODS: Clinicopathologic data of patients receiving biopsy or excision after endoscopic examination for leukoplakia from April 2009 to December 2010 were reviewed and analyzed statistically. RESULTS: A total 154 patients, 130 men and 24 women (average age, 52.60 +/- 10.86 years) were enrolled. The correlation between intraepithelium papillary capillary loop (IPCL) classification and stepwise increased severity of pathology (Pearson's r = .88, R(2) = 0.78) was significantly better than that of broadband white light images (p < .001). CONCLUSIONS: Flexible endoscopy can enhance detailed inspection of oral cavity mucosa and can be a powerful tool for examining oral leukoplakia. The IPCL patterns shown by NBI system can be helpful in detecting oral leukoplakia with higher grade dysplasia or invasive carcinoma. PMID- 22052749 TI - [Localized prostate cancer. Quo vadis?]. PMID- 22052750 TI - [Usefulness of prostatic specific antigen (PSA) for diagnosis and staging of patients with prostate cancer]. AB - The incorporation of prostatic specific antigen (PSA) to clinical practice revolutionized diagnosis and modified the epidemiology of prostate cancer(PCa). Although it lacks of many of the characteristics of an ideal tumor marker, it is the marker most used for diagnosis and follow up of any type of cancer. It represents the best clinical tool we currently have available for screening and staging of PCa. On the contrary, the greatest limitation PSA presents is its lack of tumor specificity. The use of PSA molecular derivatives and isoforms tries to solve, at least in part, its limitations. As a matter of fact, the use of % free PSA and PSAD significantly increases the test specificity for diagnosis and, the use of derivatives evaluating PSA temporary kinetics (PSAV and PSADT) represent very useful tools to estimate liquiprognosis during disease treatment and follow up. With the ongoing development of new markers for PCa, It is likely the role of PSA in diagnosis and staging of the disease will be modified. PMID- 22052751 TI - Emerging biomarkers for prostate cancer diagnosis, staging, and prognosis. AB - The introduction and widespread adoption of PSA has revolutionized the way prostate cancer is diagnosed and treated. However, the use of PSA has also led to over-diagnosis and overtreatment of prostate cancer resulting in controversy about its use for screening. PSA also has limited predictive accuracy for predicting outcomes after treatment and for making clinical decisions about adjuvant and salvage therapies. Hence, there is an urgent need for novel biomarkers to supplement PSA for detection and management of prostate cancer. Despite the progress in developing new biomarkers, several obstacles remain before such biomarkers can be clinically used. These challenges include analytical and regulatory barriers, issues with study design and data analysis that lead to lack of reproducibility of promising results, and the lack of large scale trials to adequately assess the utility of promising biomarkers. In this article we discuss the challenges in biomarker research and the statistical considerations for biomarker evaluation. There is a plethora of promising blood and urine based biomarkers. For the purpose of this review, we focus on PSA derived forms, human kallikrein 2, Early Prostate Cancer Antigen, Transforming Growth Factor-Beta 1 and Interleukin-6, Endoglin, PCA3, AMACR and ETS Gene Fusions. These biomarkers have shown promise in early studies and are at various stages of development. However, in the future it is very likely that a panel of biomarkers will be used to achieve sufficient degree of certainty in order to guide clinical decisions. To be able to be used commercially such a panel will have to answer clinically relevant questions in a simple and cost-effective way. PMID- 22052752 TI - Active surveillance: pitfalls to consider. AB - With the pendulum swinging in low risk prostate cancer (PCa) to ideas of overtreatment and overdiagnosis more urologists are looking at Active Surveillance (AS) as a valid option for their low risk PCa patients. AS will undoubtedly hold a place as a management option in men with low risk PCa, however, it is critical to understand its limitations in its current form as highlighted in this article. We conducted a review of multiple computerized databases (Ovid, Medline, Pubmed, CINAHL, Cohrane Library database) with the keywords active surveillance, prostate neoplasm, and low risk PCa. Manual searches were also carried out. Assumptions of AS are discussed and their implications on selecting the appropriate AS candidate. As with any active treatment option offered to patients with PCa, those who are offered AS must be appropriately selected and counseled as to its risks and benefits. PMID- 22052753 TI - [Epidemiological fundamentals of clinically localized prostate cancer]. AB - Prostate cancer is the sixth most common cancer in the world (in the number of new cases), the third most common cancer in men, and the most common cancer in men in Europe, North America, and some parts of Africa. Different geographical regions have varying incidence and mortality. The risk of prostate cancer is increased by African-American ethnicity, increasing age, positive family history, and other factors such as diet. Nonetheless, the causes of prostate cancer are not well understood compared with other common cancers like lung and breast cancer. The introduction of prostate-specific antigen (PSA) screening made an enormous impact on the incidence of prostate cancer, which increased in the early 1990s and is currently down to pre-PSA screening levels. Screening has caused a change in pattern of disease to an earlier stage but not lower grade. Yet we know little about what causes this disease, in the past 10 years interest in and funding for prostate cancer research have increased and several promising risk modifiers have been identified-eg, genetic predisposition, insulin growth factor (IGF) concentrations, and lycopene consumption. PMID- 22052754 TI - The precise role of ethnicity and family history on aggressive prostate cancer: a review analysis. AB - Review analysis of prostate cancer among men of sub-Saharan West African descent in comparison to other ethnicities and men with a family history of prostate cancer. PMID- 22052755 TI - Diet and prostate cancer - a holistic approach to management. AB - There is now increasing evidence from epidemiologic surveys and from laboratory, intervention, and case-control studies that diet and lifestyle plays a crucial role in prostate cancer biology and tumorigenesis. This applies to both the development and progression of prostate cancer, although in many cases the specific initiating factors in the diet are poorly understood. Conversely, many nutrients and herbs also show significant promise in helping to treat prostate cancer by slowing progression and reducing recurrence, ultimately reducing the risk of morbidity and mortality from the disease. Furthermore for all grades of prostate cancer, nutritional interventions complement conventional treatment to improve response and quality of life. Slowing or even reversing the progression of, high-grade prostate intraepithelial neoplasia [HGPIN]). with chemo preventative agents could be the best primary defense against prostate cancer, preventing it from occurring in the first place. The information given in this review about prostate cancer chemoprevention summarizes the key evidence for the role of different dietary components and their effect on prostate cancer prevention and progression. Most nutritional chemoprevention agents also have the added benefit of being beneficial for the cardiovascular system, bone health and for the prevention of other cancers. PMID- 22052756 TI - [Prostate biopsy: Diagnostic responsibility and recent changes]. AB - In this bibliographic review we reexamine the different features in relation to indication, performance and interpretation of prostatic biopsy (PB). The main objective is to place methodological features involving PB in the current scientific scenario, establishing the correlation between the most relevant and analyzing the historic evolution this procedure has followed, particularly over the last two decades. Prostate biopsy has evolved to be a regular element in urologists' daily practice and its learning process has been simplified to the point it can be approached with adequacy during the first years of residency in Urology. This privileged position PB enjoys in daily practice and the performance obtained from it would have not been a reality without optimization of transrectal ultrasound or local anesthesia techniques, yet reviled in some forums, the real responsible of such success. The consensus reached in the various scientific associations, the clinical guidelines of which are widely consulted worldwide, is the best to support the current state of the art, being the starting point for the addition of new improvements to PB. PMID- 22052757 TI - How does endorectal MRI, PET-CT and transrectal ultrasound contribute to diagnosis and management of localized prostate cancer. AB - We analyze the main imaging techniques (transrectal ultrasound, Magnetic Resonance Imaging and Position Emission Tomography) that are currently used in the diagnosis and management of localised prostate cancer patients. We analyze the results that may be obtained with transrectal US and describe the latest advances in this technique (Doppler, power doppler and contrast media). With Magnetic Resonance Imaging, we describe the underlying principles, results and indications as well as some new applications (diffusion, perfusion, spectroscopy and the use of lymphotrophic nanoparticles). Finally we will describe the current state of positron emission tomography in diagnosis, follow up and recurrence detection using the different radiomarkers that are available. PMID- 22052758 TI - [Impact of predictive models and decision making in prostate cancer: An integral debate]. AB - OBJECTIVES: To review the various methods to predict the risk of having prostate cancer, or that localized disease may be cured or progress after a given treatment. METHODS: We performed a review of the various mathematic models known for the probability analysis of the event, with a critical analysis of weaknesses and strengths of each method. In a Medline update we review the most relevant papers referred to diagnosis and management of localized prostate cancer in its diagnosis and management sides, as well as the probability of developing metastatic disease and to die. RESULTS: There are multiple methods and models to predict the various events in a patient candidate to diagnosis of prostate cancer, as well as to analyze the possibilities of success of a specific treatment, in many cases with an important exactness. We emphasize the heterogeneity in the methods, data and variables used for the analysis, basically about retrospective studies. Many of the most sophisticated methods, Neural Network or cart, do not present greater exactness than classic methods like logistic regression. CONCLUSIONS: Predictive models are an important element for decision making in usual clinical practice, favoring the decision of a diagnosis or certain treatment is not taken in a random manner and therefore it is taken following scientific criteria. Waiting for more precise methods, we have to know no method is perfect, and therefore it is an important tool, which should not by pass personal knowledge or the experience of a specific working group. PMID- 22052759 TI - Personalized approach to prostate cancer prognosis. AB - Personalized medicine in the management of patients with prostate cancer consists of the integration of patient attributes such as age, genetic risk and co morbidities with specific clinical-pathologic variables including serum prostate specific antigen (PSA), imaging and features from the diagnostic prostate needle biopsy or prostatectomy specimen including tumor differentiation (i.e. Gleason), volume and extent of disease (i.e. tumor length and / or percentage, number of positive cores at diagnosis or pathologic stage post surgery including margin status). Although the development of various clinical statistical instruments such as nomograms have provided a mechanism to interrogate these variables, most urologists rely on basic prognostic features of stage, grade and PSA along with clinical judgment to define and understand individual risk and predict health outcomes. In addition, unlike other tumor types such as breast cancer, there are no routine ancillary diagnostic studies performed on the prostate needle biopsy or prostatectomy specimen to support and refine the treatment decision process for the individual patient. In this review we will provide a summary of the current practice of predictive modeling in prostate cancer and explore how technical advances in functional histology have played a role in the development and incorporation of a systems based platform for providing a patient-specific risk profile useful for clinical decision making. PMID- 22052760 TI - [The diagnosis of prostate cancer from the clinical guidelines]. AB - OBJECTIVES: To compare methodology and recommendations for the diagnosis of prostate cancer between the different clinical Guidelines currently existent. METHODS: We searched for clinical practice Guidelines published in the period 2007-2009 in the web pages of the urological scientific associations, National Guideline clearinghouse, CMA infobase, and Trip database, as well as Pub Med. We found 4 clinical practice guidelines matching the search criteria. RESULTS: All guidelines have been developed by a multidisciplinary team, performing a previous systematic review. All of them except the AUA translate the scientific evidence in recommendations, although each of them uses a different classification. Only one of them has been evaluated using the AGREE method. There are differences in the recommendation and use of diagnostic tests (PSA, digital rectal examination and prostatic biopsy) due to the fact that as a general rule they are based on low level scientific evidence. CONCLUSIONS: Recommendations for the diagnosis of prostate cancer in all clinical practice guidelines are based on low levels of evidence, except in the use of antibiotic prophylaxis and anesthesia to perform a biopsy. PMID- 22052761 TI - Active surveillance for prostate cancer: a review. AB - Active surveillance is a solution to the widely acknowledged problem of overdiagnosis and overtreatment of clinically insignificant disease which accompanies early detection of prostate cancer using PSA and biopsy. It is an approach to the management of favorable risk prostate cancer which uses the opportunity provided by the long natural history of the disease to incorporate a period of initial observation into patient management. In this review article, the rationale, criteria for patient selection, method of follow up, trigger for intervention, and results of active surveillance are reviewed. PMID- 22052762 TI - Focal therapy for clinically localized prostate cancer. AB - The stage migration for newly diagnosed prostate cancer, improvements in prostate imaging, and devices capable of inducing subtotal prostate ablation have allowed for the formal study and evaluation of focal therapy for low-risk prostate cancer. Significant limitations remain: 1) the need for more accurate pre treatment determination of cancer location, extent, and size, 2) determining appropriate methods of post-treatment surveillance and definitions of clinical progression, 3) the uncertainty whether repeat treatment, by focal or whole-gland therapy, is effective and safe. Clinical trials are ongoing to provide data on the feasibility and reliability of these new therapies, the capability of eradicating cancers, rates of secondary treatment, and impact on urinary and sexual function. PMID- 22052763 TI - Minimally invasive radical prostatectomy: transition from pure laparoscopic to robotic-assisted radical prostatectomy. AB - OBJECTIVES: The robotic-assisted laparoscopic approach to radical prostatectomy is increasingly utilized and has become well documented as an effective oncologic treatment modality. In this study, we report the initial experience of a single surgeon at a single institution with robotic-assisted laparoscopic prostatectomy (RALP) drawing a comparison to his prior experience with pure laparoscopic prostatectomy (LRP) METHODS: This is a retrospective review of surgical results from a single surgeon performing LRP and transitioning to RALP. Baseline characteristics and outcomes of two hundred seventy five patients undergoing RALP by a single, fellowship-trained, urologic oncologist were analyzed and compared to 45 patients undergoing LRP by the same surgeon. Patient, tumor, and operative characteristics as well as functional outcomes were evaluated. Validated questionnaires, including the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF), were utilized in the assessment of urinary and sexual parameters. RESULTS: Preoperative patient and tumor characteristics (age, PSA, Gleason score) were similar in both the LRP and RALP groups. Mean operative time (195 vs. 299 minutes), estimated blood loss (223 vs. 299 mL), need for blood transfusion (1.5% vs. 4.4%) and mean length of stay (1.95 vs. 2.63 days) were significantly reduced among patients undergoing RALP as compared to those undergoing LRP. In terms of functional outcomes, continence at 12 months was better among patients undergoing RALP as compared to LRP (94% vs. 82%). In preoperatively potent men undergoing bilateral nerve sparing procedures, RALP conferred 82% potency at 24 months as opposed to only 62% following LRP. CONCLUSIONS: The combination of adjustment in surgical technique from LRP to RALP along with a concurrent institutional commitment to a successful robotic surgery program, has yielded superior operative, oncologic, and functional results. PMID- 22052764 TI - The learning curve of robotic assisted laparoscopic radical prostatectomy: what is the evidence? AB - OBJECTIVE: The robotic technique has been associated with a decreased LC for radical prostatectomy. The objective is to review the literature in search of any evidence that the RALP is able to shorten the learning curve for radical prostatectomy compared to the open and pure laparoscopic techniques. METHODS: A Medline search of the English-language literature was performed to identify all papers published relating to RALP and LC. RESULTS: There is substantial variability in the RALP literature regarding the number of cases a surgeon needs to achieve and sustain in time acceptable operative times and reasonable outcomes. The information on RALP LC comes from isolated single institution reports with questionable methodological analyses. There are no studies comparing the LC of RALP with open or pure laparoscopic techniques. CONCLUSIONS: There is no reliable information to support the notion that RALP shortens the prostatectomy LC. The evidence is limited to case series, with a Level of Evidence 4. PMID- 22052765 TI - Robotic radical prostatectomy: present and future. AB - The last 10 years have witnessed unprecedented evolution regarding de surgical removal of the prostate gland. Laparoscopic radical prostatectomy broke the open paradigm and started to generate great excitement and expectations. Shortly however, robot-assisted, laparoscopic - Robotic Surgery - emerged to address a fundamental pitfall of prostate laparoscopic surgery: execution reproducibility. Today, robotic assisted laparoscopic prostatectomy is the most used surgical approach to remove the prostate gland. Consistent advantages of this technique are: a shorter convalescent state, marked decrease in blood loss and in experienced hands, shorter average surgical times. Importantly it served to highlight the importance of outcomes as ultimate judge of a procedure success. The data suggest equivalency in long-term functional and oncological outcomes, while clear advantages in the short run: perioperative outcomes with patient rapid return to productive state. That said, the major challenge for robotic surgeons still remains: establish a paradigm that breaks with the tradition and prevents biased reporting due to technology and marketing enthusiasm, but rather takes a critical approach based in prospective, controlled, randomize clinical trials. If the latter objective is reached, urologic robotic surgeons will deliver counseling based on clinical evidence delivering major progress for our Urology field. PMID- 22052766 TI - Brachytherapy for clinically localized prostate cancer: optimal patient selection. AB - The objective of this review is to present an overview of each modality and delineate how to best select patients who are optimal candidates for these treatment approaches. Prostate brachytherapy as a curative modality for clinically localized prostate cancer has become increasingly utilized over the past decade; 25% of all early cancers are now treated this way in the United States (1). The popularity of this treatment strategy lies in the highly conformal nature of radiation dose, low morbidity, patient convenience, and high efficacy rates. Prostate brachytherapy can be delivered by either a permanent interstitial radioactive seed implantation (low dose rate [LDR]) or a temporary interstitial insertion of iridium-192 (Ir192) afterloading catheters. The objective of both of these techniques is to deliver a high dose of radiation to the prostate gland while exposing normal surrounding tissues to minimal radiation dose. Brachytherapy techniques are ideal to achieve this goal given the close proximity of the radiation source to tumor and sharp fall off of the radiation dose cloud proximate to the source. Brachytherapy provides a powerful means of delivering dose escalation above and beyond that achievable with intensity modulated external beam radiotherapy alone. Careful selection of appropriate patients for these therapies, however, is critical for optimizing both disease related outcomes and treatment-related toxicity. PMID- 22052767 TI - External beam radiation therapy for clinically localized prostate cancer: when and how we optimize with concurrent hormonal deprivation. AB - Androgen deprivation plays a major role in the treatment of prostate cancer.Preclinical studies have shown that androgen deprivation provides both an independent cytotoxic effect and radiosensitization on prostate tumors. For men with non-metastatic prostate cancer, the addition of androgen deprivation to radiotherapy has been shown to improve survival for intermediate and high risk disease compared to radiation alone.This review discusses the clinical trial data regarding combination of androgen deprivation and radiation and provides recommendations for its use in men undergoing radiotherapy for localized prostate cancer. PMID- 22052768 TI - Pyrethroid insecticide tolerance in bean leaf beetle, Cerotoma trifurcata, in the Mississippi Delta. AB - BACKGROUND: Pyrethroid insecticides have historically been effective for controlling bean leaf beetles in soybeans. Perceived field efficacy in the Mississippi Delta region has been lower over the past several years. Laboratory and field data were collected to determine whether there has been a reduction in pyrethroid insecticide susceptibility. RESULTS: Laboratory and field data both confirmed that control of bean leaf beetles with pyrethroid insecticides is poorer in the Delta regions of Mississippi and Louisiana than in all other regions tested. However, it was not possible to show that this reduced susceptibility changed over time. Furthermore, insect movement appeared to make insecticide susceptibility regional, so that localized insecticide applications had little impact on the susceptibility of successive generations. CONCLUSION: Lack of field control owing to low efficacy of pyrethroid insecticides against bean leaf beetle populations in the Delta region should be expected. Selection pressure on a regional basis may further decrease efficacy. Carbamate insecticides generally still provide high levels of control. PMID- 22052769 TI - Synthesis, crystal and electronic structures, and magnetic properties of LiLn9Mo16O35 (Ln = La, Ce, Pr, and Nd) compounds containing the original cluster Mo16O36. AB - The new compounds LiLn(9)Mo(16)O(35) (Ln=La, Ce, Pr, and Nd) were synthesized from stoichiometric mixtures of Li(2)MoO(4), Ln(2)O(3), Pr(6)O(11) or CeO(2), MoO(3), and Mo heated at 1600 degrees C for 48 h in a molybdenum crucible sealed under a low argon pressure. The crystal structure, determined from a single crystal of the Nd member, showed that the main building block is the Mo(16)O(36) unit, the Mo(16) core of which is totally new and results from the fusion of two bioctahedral Mo(10) clusters. It can also be viewed as a fragment of an infinite twin chain of edge-sharing Mo(6) octahedra. The Mo(16)O(36) cluster units share some oxygen atoms to form infinite chains running parallel to the b axis, which are separated by the rare-earth and lithium cations. (7)Li-NMR experiments, carried out at high field on the nonmagnetic LiLa(9)Mo(16)O(35), provided insights into the local environment of the lithium ions. Magnetic susceptibility measurements confirmed the trivalent oxidation state of the magnetic rare-earth cations and indicated the absence of localized moments on the Mo(16) clusters. The electronic structure of the LiLn(9)Mo(16)O(35) compounds was analyzed using molecular and periodic quantum calculations. The study of the molecular orbital diagrams of isolated Mo(16)O(36) models allowed the understanding of this unique metallic architecture. Periodic density functional theory calculations demonstrated that few interactions occur between the Mo(16) clusters, and predicted semiconducting properties for LiLn(9)Mo(16)O(35) as a band gap of 0.57 eV was computed for the lanthanum phase. PMID- 22052770 TI - SERS effects in silver-decorated cylindrical nanopores. AB - Optimization of pore diameter, the placement of nanoparticles, and the transmission of surface-enhanced Raman scattering (SERS) substrates are found to be very critical for achieving high SERS activity in porous alumina-membrane based substrates. SERS substrates with a pore diameter of 355 nm incorporating silver nanoparticles show very high SERS activity with enhancement factors of 10(10) . PMID- 22052771 TI - Mast cell-airway smooth muscle crosstalk: the role of thymic stromal lymphopoietin. AB - BACKGROUND: The mast cell localization to airway smooth muscle (ASM) bundle in asthma is important in the development of disordered airway physiology. Thymic stromal lymphopoietin (TSLP) is expressed by airway structural cells. Whether it has a role in the crosstalk between these cells is uncertain. We sought to define TSLP expression in bronchial tissue across the spectrum of asthma severity and to investigate the TSLP and TSLP receptor (TSLPR) expression and function by primary ASM and mast cells alone and in coculture. METHODS: TSLP expression was assessed in bronchial tissue from 18 subjects with mild to moderate asthma, 12 with severe disease, and nine healthy control subjects. TSLP and TSLPR expression in primary mast cells and ASM was assessed by immunofluorescence, flow cytometry, and enzyme linked immunosorbent assay, and its function was assessed by calcium imaging. The role of TSLP in mast cell and ASM proliferation, survival, differentiation, synthetic function, and contraction was examined. RESULTS: TSLP expression was increased in the ASM bundle in mild-moderate disease. TSLP and TSLPR were expressed by mast cells and ASM and were functional. Mast cell activation by TSLP increased the production of a broad range of chemokines and cytokines, but did not affect mast cell or ASM proliferation, survival, or contraction. CONCLUSIONS: TSLP expression by the bronchial epithelium and ASM was upregulated in asthma. TSLP promoted mast cell synthetic function, but did not contribute to other functional consequences of mast cell-ASM crosstalk. PMID- 22052772 TI - Predicting cardiac arrest on the wards: a nested case-control study. AB - BACKGROUND: Current rapid response team activation criteria were not statistically derived using ward vital signs, and the best vital sign predictors of cardiac arrest (CA) have not been determined. In addition, it is unknown when vital signs begin to accurately detect this event prior to CA. METHODS: We conducted a nested case-control study of 88 patients experiencing CA on the wards of a university hospital between November 2008 and January 2011, matched 1:4 to 352 control subjects residing on the same ward at the same time as the case CA. Vital signs and Modified Early Warning Scores (MEWS) were compared on admission and during the 48 h preceding CA. RESULTS: Case patients were older (64 +/- 16 years vs 58 +/- 18 years; P = .002) and more likely to have had a prior ICU admission than control subjects (41% vs 24%; P = .001), but had similar admission MEWS (2.2 +/- 1.3 vs 2.0 +/- 1.3; P = .28). In the 48 h preceding CA, maximum MEWS was the best predictor (area under the receiver operating characteristic curve [AUC] 0.77; 95% CI, 0.71-0.82), followed by maximum respiratory rate (AUC 0.72; 95% CI, 0.65-0.78), maximum heart rate (AUC 0.68; 95% CI, 0.61-0.74), maximum pulse pressure index (AUC 0.61; 95% CI, 0.54-0.68), and minimum diastolic BP (AUC 0.60; 95% CI, 0.53-0.67). By 48 h prior to CA, the MEWS was higher in cases (P = .005), with increasing disparity leading up to the event. CONCLUSIONS: The MEWS was significantly different between patients experiencing CA and control patients by 48 h prior to the event, but includes poor predictors of CA such as temperature and omits significant predictors such as diastolic BP and pulse pressure index. PMID- 22052773 TI - Association of reduced total lung capacity with mortality and use of health services. AB - BACKGROUND: Pulmonary restriction is associated with increased mortality in adults, especially those who are elderly. Previous studies, however, have used the FVC as a surrogate for the total lung capacity (TLC). We evaluated the association between a reduced TLC, mortality, and health-care resources use and compared this association with a reduced FVC. METHODS: Seven hundred fifty-two patients > 60 years old and undergoing spirometry were recruited. The main analyses were performed in patients without bronchial obstruction (n = 405). Data on mortality and admission to acute care hospitals were derived. Pulmonary restriction was alternatively defined as a TLC or an FVC below the lower limit of normal (LLN). The unadjusted relative risk of mortality associated with pulmonary restriction and adjusted incidence rate ratios (IRRs) were determined. Survival analysis was repeated using time to first hospital admission as the dependent variable. RESULTS: Overall mortality was significantly higher in the group with reduced TLC compared with the group with lower FVC (10.2 per 100 patients vs 4.27 per 100 patients, respectively), with mortality rate ratios of 6.87 (95% CI, 2.54 18.24) and 2.73 (95% CI, 1.04-7.66), respectively. After adjustment, the hazard ratio (HR) for mortality associated with pulmonary restriction in patients who received diagnoses using the FVC was reduced to 2.05 (95% CI, 0.70-6.02). Reduced TLC remained strongly associated with mortality (HR, 4.52; 95% CI, 1.32-15.51). No association was found between restriction (diagnosed using either parameter) and risk for hospitalization. CONCLUSIONS: Reduced TLC is strongly associated with mortality in adults who are elderly. Reduction of the FVC is a weaker risk factor for mortality. PMID- 22052774 TI - Prevalence of Chlamydia trachomatis, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma urealyticum infections and seminal quality in infertile and fertile men in Kuwait. AB - This study was undertaken to determine the prevalence of Chlamydia trachomatis, mycoplasmas, and ureaplasmas in semen samples of infertile compared with fertile men and to evaluate the seminological variables of semen from infected and noninfected men. A total of 127 infertile and 188 fertile men seen in a maternity hospital clinic were recruited into the study over a period of 14 months. Specimens were obtained by masturbation and examined for the presence of Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, and C trachomatis by polymerase chain reaction. Semen analysis was performed according to World Health Organization guidelines. U urealyticum, M hominis, M genitalium, and C trachomatis were demonstrated in the semen samples of 31 (24.4%) vs 49 (26.1%), 22 (17.1%) vs 61 (32.4%), 6 (4.7%) vs 6 (3.2%), and 5 (3.9%) vs 7 (3.7%), respectively, of infertile and control men. Mixed infections were detected in 14 (11%) of infertile and 29 (15.4%) of fertile men. The infertile men positive for M hominis had semen samples that showed statistically significant differences in the mean of sperm pH and leukocyte count between infected and uninfected men (P < .03 and P < .001, respectively). Similarly, there was statistically significant difference in the leukocyte counts of M genitalium and C trachomatis in infected compared with uninfected men. A similar trend was noted in infected fertile compared with uninfected men. The difference in prevalence of these urogenital pathogens among infertile compared with fertile men was not statistically significant. However, genital mycoplasmas and chlamydial infections appeared to influence semen quality negatively. PMID- 22052775 TI - Effects of castration and hormone replacement in the urinary bladder of rats: structural, ultrastructural, and biochemical analysis. AB - We evaluated, by qualitative and quantitative methods, the structural alterations in the bladder wall of rats submitted to surgical castration, as well as the role of hormone replacement in reversing the possible structural alterations. Twenty-four 12-week-old male Sprague-Dawley rats were used. The animals were divided into 3 groups comprising 8 animals each and treated as follows. Members of group CONTR (control) underwent a sham operation only and were sacrificed after 2 months. Members of group ORCH (orchiectomy) underwent bilateral orchiectomy and were sacrificed after 2 months. Members of group ORCH+TEST (testosterone) underwent orchiectomy, received testosterone replacement after 1 month, and were sacrificed 1 month later. We performed a qualitative and quantitative analysis of collagen by light microscopy, scanning electron microscopy, biochemistry, and a histomorphometric analysis of smooth muscle and elastic fibers in the 3 groups. The results showed a significant decrease in absolute values of elastic fibers in the castrated group. The histomorphometric analysis of epithelial height did not show differences among the groups. There was no statistical difference in quantitative analysis of collagen, either by histomorphometry or by biochemistry. Also, there was no difference in the smooth muscle cells. However, the qualitative analysis revealed differences in collagen (castrated group) when compared with controls and with rats submitted to hormone replacement. Hormone replacement with testosterone was able to revert the alterations observed. The findings suggest that hormone replacement, even when instituted at a late stage, is effective in reversing the bladder wall alterations produced by secondary hypogonadism. PMID- 22052776 TI - The origin of lymphatic capillaries in murine testes. AB - It is known that the seminiferous tubules are bathed in a sea of lymph in mice, which are commonly used in reproductive and immunological studies. Although testicular lymphatic vessels arising from the tunica albuginea can be macroscopically observed in mice, the exact distribution of the lymphatic capillaries remains unclear. In the present study, we investigated the distribution of lymphatic capillaries in normal testes by immunohistochemical staining with monoclonal antibodies against lymph vessel endothelium HA-receptor 1 (LYVE-1) and a platelet endothelial cell adhesion molecule (CD31). Moreover, normal lymphocytes were locally injected into the testes of recipient mice, and their migration was investigated with the use of LYVE-1 and CD31. The results showed that lymphatic capillaries were in and just beneath the tunica albuginea but not in the interstitium between the seminiferous tubules. It was also noted that these were abundant in the thickened tunica albuginea adjacent to the epididymis, but they were scarce in the thin tunica albuginea opposite the epididymis. When normal lymphocytes were locally injected into testes, the injected lymphocytes migrated between the seminiferous tubules and then drained into the lymphatic vessels in the tunica albuginea. These results suggest that tissue fluid might drain from lymphatic capillaries that arise just beneath the tunica albuginea. PMID- 22052777 TI - Statins and erectile dysfunction: a critical summary of current evidence. AB - Recently, it was reported that the administration of statins (lipid-lowering drugs) is associated with reduced levels of testosterone, and this evidence has opened a debate on the consequences these widely used drugs might have on the quality of erection. This is a very important clinical problem because patients with dyslipidemia are at increased risk of developing erectile dysfunction (ED); hence, statins exert a protective effect. At the same time, the administration of these drugs reduce endothelial dysfunction, a key etiopathogenetic factor in the onset of ED. Moreover, statins are universally considered a key element of secondary prevention for vascular events; therefore, several points are opened. In this critical summary, we attempt to evaluate the effects of statins on ED and to understand the mechanisms through which statins improve the quality of erection and the possible synergism with V phosphodiesterase inhibitors, drugs largely used for the treatment of ED. PMID- 22052778 TI - Sperm chromatin structure components are differentially repaired in cancer survivors. AB - Chemotherapy is often associated with male infertility. Our aim was to determine the effect of chemotherapy on sperm chromatin quality in cancer survivors. Sixteen men with advanced testicular cancer and 15 with Hodgkin lymphoma requiring chemotherapy were compared with 11 community volunteers. Eleven idiopathic infertile men with abnormal sperm chromatin were included as a positive control group. Semen analysis and sperm chromatin quality were determined prechemotherapy and at 6, 18, and 24 months posttreatment. DNA damage was determined by the sperm chromatin structure assay (SCSA). The level of DNA compaction was assayed by determining high DNA stainability (HDS, SCSA), the percentage of free thiols (monobromobimane-labeling assay), and the level of protamination (chromomycin A3-labeling assay). Sperm concentration and motility were dramatically decreased in cancer patients 6-18 months after chemotherapy compared with community volunteers but were not statistically different from community volunteers at 24 months posttreatment. High levels of DNA damage were observed prechemotherapy, with a tendency to remain high during the 24-month posttreatment period in testicular cancer patients; low DNA compaction (HDS, SCSA) persisted in testicular cancer patients 24 months postchemotherapy. Low levels of sperm DNA compaction were observed in cancer patients compared with community volunteers and infertile men. Sperm monobromobimane and chromomycin A3 labeling in cancer patients were similar to those from community volunteers by 18 months after treatment. Chemotherapy-induced damage to components of the sperm chromatin structure was repaired differentially over time. However, significant sperm DNA damage and low DNA compaction remained up to 24 months posttreatment. The assessment of complementary aspects of sperm chromatin quality is necessary to evaluate sperm samples in cancer survivors. PMID- 22052779 TI - Synthesis and preliminary conformational analysis of TOAC spin-labeled analogues of the medium-length peptaibiotic tylopeptin B. AB - A set of analogues of the 14-residue peptaibol tylopeptin B, containing the stable free-radical 4-amino-1-oxyl-2,2,6,6,-tetramethylpiperidine-4-carboxylic acid (TOAC) at one or two selected positions, was synthesized by the solid-phase methodology. A solution conformational analysis performed by FTIR absorption and CD suggests that, in membrane-mimicking solvents, the labeled tylopeptin B analogues preserve the helical propensity of the parent peptide, with a preference for the alpha-helix or the 3(10) -helix type depending upon the nature of the solvent. In aqueous environment, the spin-labeled analogues present a higher content of helical conformation as a consequence of the strong helix promoter effect of the conformationally constrained TOAC residue. We observed a progressive increase of the quenching effect of the nitroxyl radical on the fluorescence of the N-terminal tryptophan as TOAC replaces the Aib residue at positions 13, 8, and 4, respectively. A membrane permeabilization assay performed on two selected analogues, TOAC(8) - and TOAC(13) -tylopeptin B, showed that the labeled peptides exhibit membrane-modifying properties comparable with those of the natural peptaibiotic. We conclude that our TOAC paramagnetic analogues of tylopeptin B are good models for a detailed ESR investigation of the mechanism of membrane permeabilization induced by medium-length peptaibiotics. PMID- 22052780 TI - Near-room-temperature mid-infrared quantum well photodetector. AB - We demonstrate InGaAs mid-infrared quantum well infrared photodetectors (MIR PV QWIPs) that enable cost-effective mature GaAs-based detection and imaging technologies, with exceptional material uniformity, reproducibility, and yield, over a large area, with high spectral selectivity, innate polarization sensitivity, radiation hardness, high detectivity, and high speed operation at TEC temperatures without bias. PMID- 22052781 TI - Effects of parental number and duration of the breeding period on the effective population size and genetic diversity of a captive population of the endangered Tokyo bitterling Tanakia tanago (Teleostei: Cyprinidae). AB - The maintenance of genetic diversity is one of the chief concerns in the captive breeding of endangered species. Using microsatellite and mtDNA markers, we examined the effects of two key variables (parental number and duration of breeding period) on effective population size (N(e) ) and genetic diversity of offspring in an experimental breeding program for the endangered Tokyo bitterling, Tanakia tanago. Average heterozygosity and number of alleles of offspring estimated from microsatellite data increased with parental number in a breeding aquarium, and exhibited higher values for a long breeding period treatment (9 weeks) compared with a short breeding period (3 weeks). Haplotype diversity in mtDNA of offspring decreased with the reduction in parental number, and this tendency was greater for the short breeding period treatment. Genetic estimates of N(e) obtained with two single-sample estimation methods were consistently higher for the long breeding period treatment with the same number of parental fish. Average N(e) /N ratios were ranged from 0.5 to 1.4, and were high especially in the long breeding period with small and medium parental number treatments. Our results suggest that the spawning intervals of females and alternative mating behaviors of males influence the effective size and genetic diversity of offspring in bitterling. To maintain the genetic diversity of captive T. tanago, we recommend that captive breeding programs should be conducted for a sufficiently long period with an optimal level of parental density, as well as using an adequate number of parents. PMID- 22052782 TI - Defined presentation of carbohydrates on a duplex DNA scaffold. AB - A new method for the spatially defined alignment of carbohydrates on a duplex DNA scaffold is presented. The use of an N-hydroxysuccinimide (NHS)-ester phosphoramidite along with carbohydrates containing an alkylamine linker allows for on-column labeling during solid-phase oligonucleotide synthesis. This modification method during solid-phase synthesis only requires the use of minimal amounts of complex carbohydrates. The covalently attached carbohydrates are presented in the major groove of the B-form duplex DNA as potential substrates for murine type II C-type lectin receptors mMGL1 and mMGL2. CD spectroscopy and thermal melting revealed only minimal disturbance of the overall helical structure. Surface plasmon resonance and cellular uptake studies with bone-marrow derived dendritic cells were used to assess the capability of these carbohydrate modified duplexes to bind to mMGL receptors. PMID- 22052783 TI - Serendipitous diagnosis of mild recessive multiple epiphyseal dysplasia through parental-targeted screening test. PMID- 22052784 TI - Laccase from an alkalitolerant basidiomycetes Crinipellis sp. RCK-1: production optimization by response surface methodology. AB - A newly isolated alkalitolerant basidiomycetous fungus, identified as Crinipellis sp. RCK-1 was observed to produce laccase. The effect of different physicochemical factors on laccase production was studied. The identification of the important factors (initial pH of the medium, copper and tryptophan) with simple screening experiment involving optimization using single factor at a time strategy, was followed by application of complex response surface design for further maximizing the laccase production and was helpful in defining the effects and interactions of the physiological and nutritional factors. The statistical optimization by response surface methodology resulted in a 27.0-fold (619.9 U ml( 1)) increase in the production of laccase from Crinipellis sp. RCK-1 when compared to laccase production in unoptimized medium (23.0 U ml(-1)). The results from the response surface curve suggested that there was interaction between tryptophan and copper in a way that might resulted in positive effect on laccase production from Crinipellis sp. RCK-1. The relatively higher laccase production by Crinipellis sp. RCK-1 showed promise of offering great potential in various biotechnological applications. PMID- 22052786 TI - Cross-cultural differences in information disclosure evaluated through the EORTC questionnaires. AB - OBJECTIVE: Informational needs among cancer patients are similar, but the degree of information disclosure in different cultural areas varies. In this paper, we present the results of a cross-cultural study on information received. METHODS: The EORTC information questionnaire, EORTC QLQ-INFO25, was administered during the treatment process. This questionnaire evaluates the information that patients report they have received. Cross-cultural differences in information have been evaluated using statistical tests such as Kruskall-Wallis and multivariate models with covariates to account for differences in clinical and demographic characteristics across areas. RESULTS: Four hundred and fifty-one patients from three cultural areas, North-Middle Europe, South Europe, and Taiwan, were included in the study. Significant differences among the three cultural areas appeared in eight QLQ-INFO25 dimensions: information about the disease; medical tests; places of care; written information; information on CD/tape/video; satisfaction; wish for more information; and information helpfulness. North Middle Europe patients received more written information (mean = 67.2 (North) and 33.8 (South)) and South Europe patients received more information on different places of care (mean = 24.7 (North) and 35.0 (South)). Patients from North-Middle Europe and South Europe received more information than patients from Taiwan about the disease (mean = 57.9, 60.6, and 47.1, respectively) and medical tests (70.9, 70.4, and 54.5), showed more satisfaction (64.8, 70.2, and 35.0), and considered the information more helpful (71.9, 73.9, and 50.4). These results were confirmed when adjusting for age, education, and disease stage. CONCLUSION: There are cross cultural differences in information received. Some of these differences are based on the characteristics of each culture. PMID- 22052787 TI - High daily fraction dose external radiotherapy for T1 glottic carcinoma: treatment results and prognostic factors. AB - BACKGROUND: The purpose of this study was to investigate the prognostic factors and treatment results of T1N0M0 glottic laryngeal carcinoma irradiated with 2.3 Gray (Gy) per fraction. METHODS: A total of 183 patients with glottic carcinoma treated between June 1998 and January 2007 were retrospectively evaluated. Of the 183 patients, 163 patients (89%) had T1a and 20 patients (11%) had T1b disease. All patients received 2.3 Gy per fraction to a median total dose of 64.4 Gy. RESULTS: The median follow-up was 63 months. The 5-year overall survival (OS), local control, and cancer-specific survival rates were 89%, 81%, and 90%, respectively. Multivariate analysis showed overall treatment time and age to be significant prognostic factors for local control and OS. We observed no grade IV or grade V acute toxicity. Trachea-esophageal fistula as late toxicity was observed in only 1 patient. CONCLUSIONS: High daily fraction scheme seems to be a feasible schedule for early glottic carcinomas. PMID- 22052788 TI - A stereodivergent strategy for the preparation of corynantheine and ipecac alkaloids, their epimers, and analogues: efficient total synthesis of (-) dihydrocorynantheol, (-)-corynantheol, (-)-protoemetinol, (-)-corynantheal, (-) protoemetine, and related natural and nonnatural compounds. AB - Here we present a general and common catalytic asymmetric strategy for the total and formal synthesis of a broad number of optically active natural products from the corynantheine and ipecac alkaloid families, for example, indolo[2,3-a]- and benzo[a]quinolizidines. Construction of the core alkaloid skeletons with the correct absolute and relative stereochemistry relies on an enantioselective and diastereodivergent one-pot cascade sequence followed by an additional diastereodivergent reaction step. This allows for enantio- and diastereoselective synthesis of three out of four possible epimers of the quinolizidine alkaloids that begin from common and easily accessible starting materials by using a common synthetic route. Focus has been made on excluding protecting groups and limiting isolation and purification of synthetic intermediates. This methodology is applied in the total synthesis of the natural products (-)-dihydrocorynantheol, ( )-hirsutinol, (-)-corynantheol, (-)-protometinol, (-)-dihydrocorynantheal, (-) corynantheal, (-)-protoemetine, (-)-(15S)-hydroxydihydrocorynantheol, and an array of their nonnatural epimers. The potential of this strategy is also demonstrated in the synthesis of biologically interesting natural product analogues not accessible through synthetic elaboration of alkaloid precursors available from nature, for example, thieno[3,2-a]quinolizidine derivatives. We also report the formal synthesis of (+)-dihydrocorynantheine, (-)-emetine, (-) cephaeline, (-)-tubulosine, and (-)-deoxytubulosine. PMID- 22052789 TI - Determination of ethylene glycol dinitrate in dynamites using HPLC: application to the plastic explosive Goma-2 ECO. AB - In this study, a sequential extraction method using water and methanol to recover ethylene glycol dinitrate or nitroglycol (EGDN) contained in Goma-2 ECO dynamite was developed. After, an HPLC method was used for the determination of EGDN in the two extracted phases. The analytical method was validated by evaluating its selectivity, sensitivity, linearity, and linear working concentration range, limit of detection and quantitation, precision (as repeatability and intermediate precision), accuracy, and robustness, providing appropriate values (i.e. RSD values for precision about 6% and accuracy about 100%). Finally, the EGDN content of a sample of the Goma-2-ECO dynamite was determined obtaining a concentration of 30.29%, which is in accordance with the manufacturer's specifications for this dynamite (25.7-31.4%). PMID- 22052790 TI - Allenyl-beta-lactams: versatile scaffolds for the synthesis of heterocycles. AB - The hybrid allenic beta-lactam moiety represents an excellent building block for carbo- and heterocyclization reactions, affording a large number of cyclic structures containing different sized skeletons in a single step. This strategy has been studied under thermal and radical-induced conditions. More recently, the use of transition-metal catalysis has been introduced as an alternative that relies on the activation of the allenic component. On the other hand, the intramolecular version has attracted much attention as a strategy for the synthesis of bi- and tricyclic compounds in a regio- and stereoselective manner. This overview focuses on the most recently developed cyclizations on 2 azetidinone-tethered allenes along with remarkable early works accounting for the mechanism, as well as for the regio- and diastereoselectivities of the cyclizations. PMID- 22052791 TI - Huprine derivatives as sub-nanomolar human acetylcholinesterase inhibitors: from rational design to validation by X-ray crystallography. PMID- 22052792 TI - The structure and assembly model of the third transmembrane domain of Slc11a1 in SDS micelles revealed by NMR study of the Leu-substituted peptide. AB - Slc11a1 is an integral membrane protein with 12 putative transmembrane domains (TMDs) and functions as a pH-coupled divalent metal cation transporter. The conservation of three negatively charged residues in the TMD3 of Slc11 protein family implies the important role of this domain in the function of the proteins. However, aggregation of the transmembrane peptide in micelles prevents structural study of the peptide in these membrane-mimetic environments by NMR spectroscopy. Here, we characterized the structure, position, and assembly model of Slc11a1 TMD3 (Lys128-Ile151) in SDS micelles by the NMR study of its Leu-substituted peptide. It was found that the two-site substitutions of Ala for Leu residues at positions 136 and 140 of TMD3 disrupt the aggregation without altering the secondary structure of the peptide. The Leu-substituted peptide folds as an alpha helix spanning from Leu133 to Gly144 and embedded in the micelles. A Leu zipper is suggested to account for the self-assembly of the wild-type peptide in SDS micelles. PMID- 22052793 TI - Inkjet printing of conjugated polymer precursors on paper substrates for colorimetric sensing and flexible electrothermochromic display. AB - Inkjet-printable aqueous suspensions of conjugated polymer precursors are developed for fabrication of patterned color images on paper substrates. Printing of a diacetylene (DA)-surfactant composite ink on unmodified paper and photopaper, as well as on a banknote, enables generation of latent images that are transformed to blue-colored polydiacetylene (PDA) structures by UV irradiation. Both irreversible and reversible thermochromism with the PDA printed images are demonstrated and applied to flexible and disposable sensors and to displays. PMID- 22052794 TI - A new haplotype in BMP4 implicated in ossification of the posterior longitudinal ligament (OPLL) in a Chinese population. AB - Previous genome-wide microarray analysis of candidate genes involved in the ossification of the posterior longitudinal ligament (OPLL) of the spine resulted in the identification of a novel, clinically relevant gene encoding bone morphogenetic protein 4 (BMP4) but was defined only by its expression patterns. The complete genomic BMP4 coding DNA from 450 patients with OPLL and 550 matched controls were sequenced and compared. We identified 18 SNPs, among which the minor alleles of SNP8 (C>T; p < 0.001; OR: 1.58), SNP13 (rs17563C>T; p < 0.001; OR: 1.76), and SNP14 (rs76335800A>T; p < 0.001; OR: 1.68) were associated with OPLL. Logistic regression analysis showed that the additive model of SNP8 (p < 0.001; OR: 3.48), SNP13 (p < 0.001; OR: 2.22), and SNP14 (p < 0.001; OR: 1.99) retained statistical significance. Linkage disequilibrium (LD) analysis identified a 3-kbp block of intense LD in BMP4 and 1 specific haplotype, TGGGCTT (p < 0.001, OR: 2.54), which was associated with OPLL-associated risk alleles and increased severity of OPLL, as shown by the distribution of ossified vertebrae in patients with OPLL (p = 0.002). Novel mutations in the BMP4 gene and a specific haplotype TGGGCTT appear to contribute to the risk of developing OPLL. Also the severity of OPLL seems to be mediated predominantly by genetic variations in this specific BMP4 gene region, but might be associated with other certain clinical and demographic characteristics in the Chinese population studied. PMID- 22052795 TI - Raman spectrum in the pseudogap phase of the underdoped cuprates: effect of phase coherence and the signature of the KT-type superconducting transition. AB - The temperature evolution of the Raman spectrum of the underdoped cuprates is studied in the thermal phase fluctuation scenario with an XY-type lattice model for the phase degree of freedom. It is found that the pair breaking Raman peak depends sensitively on the phase coherence of the pairing order parameter. As a result, the integrated Raman intensity in both the B(1g) and the B(2g) channels exhibits a dramatic drop across the Kosterlitz-Thouless (KT) transition temperature (T(KT)), when vortex-like phase fluctuation is proliferated. This result, which is consistent with experimental observations, provides further support for the thermal phase fluctuation scenario of the pseudogap phase and the KT-type nature of the superconducting transition in underdoped cuprates. PMID- 22052796 TI - A de novo 3.54 Mb deletion of 17q22-q23.1 associated with hydrocephalus: a case report and review of literature. AB - We describe a female newborn with a de novo 3.54 megabase (Mb) deletion of 17q22 q23.1 (chr17:53,072,536-56,612,662, hg18) including genes from MSI2 to BCAS3 detected by oligonucleotide array comparative genomic hybridization (aCGH). Prenatal ultrasound examination noted oligohydramnios and ventriculomegaly in the fetus. Postnatal examination found hypotonia, macrocephaly, arachnodactyly of fingers and toes, dysmorphic features, bilateral hearing loss and heart defect. Review of reported cases with genomic findings noted one case with proximal deletion involving the NOG gene and a case series with distal recurrent microdeletions involving the TBX2 and TBX4 genes. Our case presented a unique deletion partially overlapped with the above deletions but not including the NOG, TBX2, and TBX4 genes. A genomic map for deletions in this 17q22-q23.1 region was constructed to further define the common deletion intervals for potential haplo insufficient genes. PMID- 22052797 TI - Asymmetric synthesis of cis-4-aminobenzopyran derivatives catalyzed by N,N' dioxide-Sc(OTf)3 complexes. PMID- 22052798 TI - Initial testing (stage 1) by the pediatric preclinical testing program of RO4929097, a gamma-secretase inhibitor targeting notch signaling. AB - RO4929097 is a potent and selective inhibitor of gamma-secretase and as a result is able to inhibit Notch pathway signaling. The activity of RO4929097 was evaluated against the in vivo panels of the Pediatric Preclinical Testing Program (PPTP). RO4929097 induced significant differences in event-free survival (EFS) distribution compared to control in 6 of 26 (23%) of the evaluable solid tumor xenografts and in 0 of 8 (0%) of the evaluable ALL xenografts. The most consistent tumor growth delay effects were noted in the osteosarcoma panel. RO4929097 at the dose and schedule evaluated demonstrated little antitumor activity against childhood cancer xenografts. PMID- 22052799 TI - Tuning HP1alpha chromodomain selectivity for di- and trimethyllysine. AB - Histone lysine methylation is a critical marker for controlling gene expression. The position and extent of methylation (mono-, di-, or tri-) controls the binding of effector proteins that determine whether the associated DNA is expressed or not. Dysregulation of histone protein methylation has been associated with a number of types of cancer, and development of inhibitors for the effector proteins is becoming an active area of research. For this reason, understanding the mechanism by which effector proteins obtain selectivity for the different methylation states of lysine is of great interest. To this end, we have performed mutation studies on the Drosophila HP1alpha chromodomain, which binds H3K9Me(2) and H3K9Me(3) with approximately equal affinities. The selectivity of HP1alpha chromodomain for H3K9Me(3) over H3K9Me(2) was investigated by mutating E52 to remove or weaken the hydrogen bond to K9Me(2) while maintaining affinity for K9Me(3,) including E52F, E52I, E52V, E52D, an E52Q. The E52Q mutant exhibited the greatest degree of selectivity for KMe3, with 3.5-fold weaker binding to the dimethylated peptide (K(D) =52 MUM) compared to the trimethylated peptide (K(D) =15 MUM). These studies provide insight into the role of electrostatic interactions and hydrogen bonding in the differentiation of methylation states and have implications regarding the evolutionary pressure for selectivity in this protein-protein interaction. Moreover, the information from this study may help guide inhibitor development for this class of proteins. PMID- 22052800 TI - Branched polyethyleneimine-bonded tentacle-type polymer stationary phase for peptides and proteins separations by open-tubular capillary electrochromatography. AB - A novel tentacle-type polymer stationary phase covalently modified with branched polyethyleneimine (PEI) was developed for peptides and proteins separations by open-tubular CEC (OT-CEC). The preparation procedure included the silanization of capillary inner wall, in situ graft polymerization and PEI functionalization. A wrinkly polymer surface of multitudinous steric amine groups was evenly formed on the capillary inner wall, and anodic EOF could be gained within a wide pH range of 2.5-7.5. The electroosmotic mobility was examined for its dependence on pH as well as PEI concentrations. Good repeatability was gained with RSD for the migration time of EOF marker within 4.8% and satisfactory chemical stability was validated. Due to the existence of amine groups on the surface of tentacle-type polymer stationary phase, the silanol effect that occurs between the positively charged biomolecules and the silanols of the capillary column was greatly suppressed. Compared with a monolayer-coating capillary, seven enkephalin-related peptides were well resolved on the PEI-bonded column with high efficiencies. Favorable separations of peptides and proteins with high column efficiencies were obtained in 144,000-189,000 and 97,000-170,000 plates/m. Branched PEI-bonded tentacle-type polymer stationary phase has been proven to afford satisfactory retention and resolution of peptides and proteins. PMID- 22052801 TI - Platinum(II) phenanthroimidazoles for targeting telomeric G-quadruplexes. AB - A rationally designed progression of phenanthroimidazole platinum(II) complexes were examined for their ability to target telomere-derived intramolecular G quadruplex DNA. Through the use of circular dichroism, fluorescence displacement assays, and molecular modeling we show that these complexes template and stabilize G-quadruplexes from sequences based on the human telomeric repeat (TTAGGG)(n). The greatest stabilization was observed for the p-chlorophenyl derivative 6((G4)DC(50) =0.31 MUM). We also show that the G-quadruplex binding complexes are able to inhibit telomerase activity through a modified telomerase repeat amplification protocol (TRAP-LIG assay). Preliminary cell studies show that complex 6 is preferentially cytotoxic toward cancer over normal cell lines, indicating its potential use in cancer therapy. PMID- 22052802 TI - Gene-environment interactions of novel variants associated with head and neck cancer. AB - BACKGROUND: A genome-wide association study for upper aerodigestive tract cancers identified 19 candidate single-nucleotide polymorphisms (SNPs). We used these SNPs to investigate the potential gene-gene and gene-environment interactions in head and neck squamous cell carcinoma (HNSCC) risk. METHODS: The 19 variants were genotyped using Taqman assays among 575 cases and 676 controls in our population based case-control study. RESULTS: A restricted cubic spline model suggested both ADH1B and HEL308 modified the association between smoking pack-years and HNSCC. Classification and regression tree analysis demonstrated a higher-order interaction between smoking status, ADH1B, FLJ13089, and FLJ35784 in HNSCC risk. Compared with ever smokers carrying ADH1B T/C+T/T genotypes, smokers carrying ADH1B C/C genotype and FLJ13089 A/G+A/A genotypes had the highest risk of HNSCC (odds ratio = 1.84). CONCLUSIONS: Our results suggest that the risk associated with these variants may be specifically important among specific exposure groups. PMID- 22052803 TI - Sialic acid and sialyl-lactose glyco-conjugates: design, synthesis and binding assays to lectins and swine influenza H1N1 virus. AB - The terminal parts of the influenza hemagglutinin (HA) receptors alpha2,6- and alpha2,3-sialyllactoses were conjugated to an artificial carrier, named sequential oligopeptide carrier (SOC(4) ), to formulate human and avian receptor mimics, respectively. SOC(4) , formed by the tripeptide unit Lys-Aib-Gly, adopts a rigid helicoids-type conformation, which enables the conjugation of biomolecules to the Lys-N(epsilon) H(2) groups. By doing so, it preserves their initial conformations and functionalities of the epitopes. We report that SOC(4) glyco-conjugate bearing two copies of the alpha2,6-sialyllactose is specifically recognized by the biotinylated Sambucus nigra (elderberry) bark lectin, which binds preferentially to sialic acid in an alpha2,6-linkage. SOC(4) -glyco conjugate bearing two copies of the alpha2,3-sialyllactose was not recognized by the biotinylated Maackia amurensis lectin, despite its well-known alpha2,3-sialyl bond specificity. However, preliminary immune blot assays showed that H1N1 virus binds to both the SOC(4) -glyco-conjugates immobilized onto nitrocellulose membrane. It is concluded that Ac-SOC(4) [(Ac)(2) ,(3'SL-Aoa)(2) ]-NH(2) 5 and Ac SOC(4) [(Ac)(2) ,(6'SL-Aoa)(2) ]-NH(2) 6 mimic the HA receptors. These findings could be useful for easy screening of binding and inhibition assays of virus receptor interactions. PMID- 22052807 TI - Pressure effects on Dirac fermions in alpha-(BEDT-TTF)2I3. AB - We investigate the pressure effect on the layered Dirac fermion system, which is realized in quasi-two-dimensional organic compound alpha-(BEDT-TTF)2I3. The trajectory of the contact points is investigated using the tight-binding model with the transfer integrals determined by x-ray diffraction experiments. Vanishing of the Dirac fermion spectrum, opening of the gap, and pressure dependence of interlayer magnetoresistance are discussed. PMID- 22052806 TI - Viscoelastic properties of human cortical bone tissue depend on gender and elastic modulus. AB - Bone exhibits rate-dependent failure behavior, suggesting that viscoelasticity is a factor in the damage and fracture of bone. Microdamage initiates at scales below the macroscopic porosity in bone, and, as such, is affected by the intrinsic viscoelasticity of the bone tissue. The viscoelasticity of the bone tissue can be measured by nanoindentation and recording the creep behavior at constant load. The viscoelastic properties have been used to assess differences in tissue behavior with respect to fracture healing, aging, and mouse strains. In this study, we compared the viscoelastic behavior of human cortical bone between genders by using nanoindentation at a fixed load of 10 mN to measure the creep time constant. Bones from females had a significantly greater time constant, indicating slower creep and relaxation, than bones from males. The creep time constants decreased with increasing tissue modulus. The mineralization, collagen content, and collagen cross-link density, which were bulk measurements, were analyzed to determine if the differences in viscoelastic behavior were explained by compositional differences in the bone. However, none of the parameters differed between genders, nor were they correlated to the viscoelastic time constant. As such, the difference must depend on other matrix proteins that we did not assess or differences in the microstructural organization. This is one of the only intrinsic bone material properties that has been found to differ between males and females, and it may be important for assessing differences in fracture risk, since crack propagation is generally sensitive to viscoelastic properties. PMID- 22052808 TI - A polymorphism in the growth hormone receptor is associated with height in children with Prader-Willi syndrome. AB - The exon-3 deletion polymorphism (d3, Database of Genomic Variants ID: Variation_64191) in the growth hormone receptor (GHR) gene is associated with increased growth response to growth hormone (GH) therapy in GH-deficient patients. However, an association of the GHR genotype with height has not yet been reported in Prader-Willi syndrome (PWS). The aim of this study was to assess the association of GHR alleles with height before starting GH therapy in patients with PWS. Seventy-four patients with PWS were genotyped and their medical records were retrospectively reviewed (45 males and 29 females, median age 8.7 years). One hundred normal controls, with known final height, were also genotyped. The GH exon 3 locus was genotyped using a PCR multiplex assay. The distribution of alleles in the patients with PWS was not different from controls [(fl/fl n = 53 (72%), fl/d3 n = 21 (28%)) in PWS vs. (fl/fl n = 72(72%), fl/d3 n = 26(26%), and d3/d3 n = 2(2%)]. However, patients with PWS carrying a d3 allele had significantly greater height standard deviation scores (SDS) (P = 0.025) and higher insulin-like growth factor I (IGF-I) level (P = 0.041), although the age at the start of GH therapy, weight, BMI, and body fat were not different. The d3 allele was associated with height and IGF-I levels before GH therapy and suggests that even before GH therapy, d3 allele may influence height through GH secretion. PMID- 22052809 TI - Influence of sugar ring conformation on the transportability of nucleosides by human nucleoside transporters. AB - The conformational preference of human nucleoside transporters (hNTs) with respect to sugar ring was examined using conformationally fixed purine and pyrimidine nucleosides built on a bicyclo[3.1.0]hexane template. These fixed conformation nucleosides, methanocarba-deoxyadenosine or methanocarba deoxycytidine in North (C3'-endo, N-MCdA and N-MCdC) or South (C2'-endo, S-MCdA and S-MCdC) conformations, were used to study inhibition of equilibrative (hENT1 4) and concentrative (hCNT1-3) nucleoside transport by individual recombinant hNTs produced in Saccharomyces cerevisiae cells or Xenopus laevis oocytes. Our results indicated that nucleosides in the North conformation were potent inhibitors of transport mediated by hCNTs whereas South nucleosides were inhibitors of hENTs, thus showing differences in the interaction with the hNTs. In summary, hCNTs exhibited strong preferences for North nucleosides whereas hENTs exhibited slight preferences for South nucleosides, demonstrating for the first time different conformational preferences among members of the two families of hNTs. PMID- 22052810 TI - TP53 codon 72 polymorphisms in favorable histology Wilms tumors. AB - In Wilms tumor (WT), mutations in the gene encoding p53, TP53, are correlated with anaplasia; however TP53 variants have not been studied in favorable histology (FH) WTs. A single nucleotide polymorphism of TP53 encoding either arginine or proline at codon 72 is suggested to alter in vitro p53 behavior. Therefore, we analyzed tissue from 23 consecutive patients with FHWT to determine allelic and genotypic frequencies of Pro72 and Arg72 variants and correlate this with clinical outcomes. Interestingly, our cohort showed a statistically significant over-representation of the Arg allele and Arg/Arg genotype. However, the genotypic and allelic frequencies showed no significant correlation with age, stage, or disease recurrence. PMID- 22052811 TI - Galloflavin (CAS 568-80-9): a novel inhibitor of lactate dehydrogenase. AB - One of the most prominent alterations in cancer cells is their strict dependence on the glycolytic pathway for ATP generation. This observation led to the evaluation of glycolysis inhibitors as potential anticancer agents. The inhibition of lactate dehydrogenase (LDH) is a promising way to inhibit tumor cell glucose metabolism without affecting the energetic balance of normal tissues. However, the success of this approach depends chiefly on the availability of inhibitors that display good selectivity. We identified a compound (galloflavin, CAS 568-80-9) which, in contrast to other inhibitors of human LDH, hinders both the A and B isoforms of the enzyme. To determine the mechanism of action, we collected LDH-A and -B inhibition data in competition reactions with pyruvate or NADH and evaluated the results using software for enzyme kinetics analysis. We found that galloflavin inhibits both human LDH isoforms by preferentially binding the free enzyme, without competing with the substrate or cofactor. The calculated Ki values for pyruvate were 5.46 MUM (LDH A) and 15.06 MUM (LDH-B). In cultured tumor cells, galloflavin blocked aerobic glycolysis at micromolar concentrations, did not interfere with cell respiration, and induced cell death by triggering apoptosis. To our knowledge, the inhibition of LDH is, to date, the only biochemical effect described for galloflavin. Because galloflavin is not commercially available, we also describe herein a procedure for its synthesis and report its first full chemical characterization. PMID- 22052812 TI - Cloning and expression of a retinoic acid receptor beta2 subtype from the adult newt: evidence for an early role in tail and caudal spinal cord regeneration. AB - Retinoic acid receptor beta 2 (RARbeta2) has been proposed as an important receptor mediating retinoid-induced axonal growth and regeneration in developing mammalian spinal cord and brain. In urodele amphibians, organisms capable of extensive central nervous system (CNS) regeneration as adults, this receptor had not been isolated, nor had its function been characterized. We have cloned a full length RARbeta2 cDNA from adult newt CNS. This receptor, NvRARbeta2, is expressed in various adult organs capable of regeneration, including the spinal cord. Interestingly, both the NvRARbeta2 mRNA and protein are up-regulated during the first 2 weeks after amputation of the tail, primarily in the ependymoglial and meningeal tissues near the rostral cut surface of the cord. Treatment with LE135, a RARbeta-selective antagonist, caused a significant inhibition of ependymal outgrowth and a decrease in tail regenerate length. These data support an early role for this receptor in caudal spinal cord and tail regeneration in this amphibian. PMID- 22052813 TI - Reversible photooxygenation of alkynylanthracenes: chemical generation of singlet oxygen under very mild conditions. PMID- 22052814 TI - Preparative isolation and purification of senkyunolide-I, senkyunolide-H and ferulic acid from Rhizoma Chuanxiong using counter-current chromatography. AB - Three active compounds, senkyunolide-I, senkyunolide-H and ferulic acid (FA), were successfully isolated and purified from the extracts of Rhizoma Chuanxiong by counter-current chromatography (CCC). Based on the principle of the partition coefficient values (k) for target compounds and the separation factor (alpha) between target compounds, the two-phase solvent system that contains n-hexane ethyl acetate-methanol-water at an optimized volume ratio of 3:7:4:6 v/v was selected for the CCC separation, and the lower phase was employed as the mobile phase in the head-to-tail elution mode. In a single run, 400 mg of the crude extract yielded pure senkyunolide-I (6.4 mg), senkyunolide-H (1.7 mg) and FA (4.4 mg) with the purities of 98, 93 and 99%, respectively. The CCC fractions were analyzed by high-performance liquid chromatography, and the structures of the three active compounds were identified by MS and (1)H NMR. PMID- 22052815 TI - Detection of nonopioid beta-endorphin receptor in the rat myocardium. AB - Two selective agonists of nonopioid beta-endorphin receptor, synthetic peptides TPLVTLFK (octarphin) and SLTCLVKGFY (immunorphin), were labeled with tritium to specific activity of 29 and 25 Ci/mmol, respectively. Both labeled peptides were found to bind to high-affinity naloxone-insensitive binding sites on the membranes isolated from the rat myocardium (Kd = 2.0 +/- 0.2 and 2.5 +/- 0.3 nM, respectively). The [(3)H]octarphin specific binding to the myocardial membranes was inhibited by unlabeled beta-endorphin (Ki = 1.9 +/- 0.2 nM) and immunorphin (Ki = 2.2 +/- 0.3 nM). The [(3)H]immunorphin specific binding with the membranes was inhibited by unlabeled beta-endorphin (Ki = 2.3 +/- 0.3 nM) and octarphin (Ki = 2.4 +/- 0.3 nM). The binding specificity study revealed that these binding sites were insensitive not only to naloxone but also to alpha-endorphin, gamma endorphin, [Met(5)]enkephalin and [Leu(5)]enkephalin. Thus, beta-endorphin, immunorphin and octarphin bind to the common high-affinity naloxone-insensitive receptor of the rat myocardial membranes. PMID- 22052816 TI - Chemoradiation for patients with large-volume laryngeal cancers. AB - BACKGROUND: Patients with T4 laryngeal cancers, including those with large-volume (cartilage or tongue-base invasion) lesions, are often excluded from organ preservation trials due to expectations of inferior outcome in terms of survival and function. We hypothesize that such patients indeed have acceptable survival and function when treated with organ-preservation strategies. METHODS: Retrospective analysis of prospectively collected data of a cohort of patients with T4 laryngeal cancer was carried out. Follow-up ranged from 0.18 to 15.6 years. All T4 laryngeal cancer patients who were enrolled in the University of Chicago concomitant chemoradiotherapy protocols from 1994 to the present were reviewed. This study was composed of 80 newly diagnosed T4 laryngeal cancer patients. Efficacy of treatment was determined through evaluations of survival and function. Survival was evaluated via Kaplan-Meier methods. Swallowing function was evaluated by an oropharyngeal motility (OPM) study and swallowing scores were assigned. Higher scores reflected increasing swallowing dysfunction. RESULTS: Fifty-five of 80 patients (~69%) had documented large-volume tumor. Two- and 5-year overall survivals were 60.0% and 48.7%, respectively. Disease-specific 2- and 5-year survivals for the group were 80.1% and 71.3%, and 79.4 and 74.3%, respectively, for the 55 patients with large volume status. Progression-free survival rates were 52.6% and 47.6%. Forty-four of 65 patients (~68%) with OPM data had a Swallowing Performance Status Scale (SPSS) score of <=5, indicating various degrees of swallowing abnormalities not requiring a gastrostomy tube. This is a functional-preservation rate of 67.7%. CONCLUSIONS: Chemoradiation for patients with T4 laryngeal cancer appears to be an effective and reasonable option, particularly in light of the satisfactory survival and function preservation rates. PMID- 22052818 TI - Anisotropic intrinsic spin Hall effect in quantum wires. AB - We use numerical simulations to investigate the spin Hall effect in quantum wires in the presence of both Rashba and Dresselhaus spin-orbit coupling. We find that the intrinsic spin Hall effect is highly anisotropic with respect to the orientation of the wire, and that the nature of this anisotropy depends strongly on the electron density and the relative strengths of the Rashba and Dresselhaus spin-orbit couplings. In particular, at low densities, when only one subband of the quantum wire is occupied, the spin Hall effect is strongest for electron momentum along the [N110] axis, which is the opposite of what is expected for the purely 2D case. In addition, when more than one subband is occupied, the strength and anisotropy of the spin Hall effect can vary greatly over relatively small changes in electron density, which makes it difficult to predict which wire orientation will maximize the strength of the spin Hall effect. These results help to illuminate the role of quantum confinement in spin-orbit-coupled systems, and can serve as a guide for future experimental work on the use of quantum wires for spin-Hall-based spintronic applications. PMID- 22052817 TI - Metal-ion-dependent folding of a uranyl-specific DNAzyme: insight into function from fluorescence resonance energy transfer studies. AB - Fluorescence resonance energy transfer (FRET) has been used to study the global folding of an uranyl (UO(2)(2+))-specific 39E DNAzyme in the presence of Mg(2+), Zn(2+), Pb(2+), or UO(2)(2+). At pH 5.5 and physiological ionic strength (100 mM Na(+)), two of the three stems in this DNAzyme folded into a compact structure in the presence of Mg(2+) or Zn(2+). However, no folding occurred in the presence of Pb(2+) or UO(2)(2+); this is analogous to the "lock-and-key" catalysis mode first observed in the Pb(2+)-specific 8-17 DNAzyme. However, Mg(2+) and Zn(2+) exert different effects on the 8-17 and 39E DNAzymes. Whereas Mg(2+) or Zn(2+) dependent folding promoted 8-17 DNAzyme activity, the 39E DNAzyme folding induced by Mg(2+) or Zn(2+) inhibited UO(2)(2+)-specific activity. Group IIA series of metal ions (Mg(2+), Ca(2+), Sr(2+)) also caused global folding of the 39E DNAzyme, for which the apparent binding affinity between these metal ions and the DNAzyme decreases as the ionic radius of the metal ions increases. Because the ionic radius of Sr(2+) (1.12 A) is comparable to that of Pb(2+) (1.20 A), but contrary to Pb(2+), Sr(2+) induces the DNAzyme to fold under identical conditions, ionic size alone cannot account for the unique folding behaviors induced by Pb(2+) and UO(2)(2+). Under low ionic strength (30 mM Na(+)), all four metal ions (Mg(2+), Zn(2+), Pb(2+), and UO(2)(2+)), caused 39E DNAzyme folding, suggesting that metal ions can neutralize the negative charge of DNA-backbone phosphates in addition to playing specific catalytic roles. Mg(2+) at low (<2 mM) concentration promoted UO(2)(2+)-specific activity, whereas Mg(2+) at high (>2 mM) concentration inhibited the UO(2)(2+)-specific activity. Therefore, the lock and-key mode of DNAzymes depends on ionic strength, and the 39E DNAzyme is in the lock-and-key mode only at ionic strengths of 100 mM or greater. PMID- 22052819 TI - A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopia. AB - We report on a follow-up evaluation of a male with a phenotype including craniosynostosis, periventricular nodular heterotopia, and neurodevelopmental delay. He was initially assigned a clinical diagnosis of Fontaine-Farriaux syndrome (FFS) as an infant although now, with improved delineation of this entity, it is evident that this diagnosis is not applicable to this individual. Array comparative genomic hybridization has demonstrated a 300 kb interstitial deletion on Xp22.11 affecting all or part of three annotated genes, ZFX, PDK3, and PCYT1B in this subject. The deletion was inherited from the phenotypically normal mother who also exhibited markedly skewed X-inactivation. These findings implicate hemizygosity for one or all three of these genes as the cause of this phenotype. PMID- 22052820 TI - Self-assembly of linear and cyclic siloxane-containing mesogens: investigation of layered structures in bulk and thin films. AB - Silicon-containing materials which possess the ability to form mesophases are promising systems for applications in the fields of electro-optical devices, nonlinear optics, and information storage media. In this work, the formation of supramolecular assemblies of a series of low molecular weight siloxane-containing mesogens is presented. Besides a novel synthesis route via Ru(II) -catalyzed hydrosilylation of phenyl acetylene derivatives, mesophase characterization by modern analysis techniques is performed. As linker groups, leading to bi- and tetramesogens, linear disiloxane and cyclic tetrasiloxane are utilized. In the resulting class of materials, high thermal stability, induced by the formation of layered smectic-type structures, is predominant. The smectic-type phases were found to be monotropic. Layer distances in the assemblies, as well as the phase transition temperatures, can be controlled by the substitution motif on the mesogens (number and length of alkyl chains). In spin-cast thin films, the layered domains are visualized by atomic force microscopy; furthermore, domain dimensions and electron densities are determined by grazing-incidence small-angle X-ray scattering. PMID- 22052821 TI - Induction of canonical Wnt signaling by alsterpaullone is sufficient for oral tissue fate during regeneration and embryogenesis in Nematostella vectensis. AB - Although regeneration is widespread among metazoa, the molecular mechanisms have been studied in only a handful of taxa. Of these taxa, fewer still are amenable to studies of embryogenesis. Our understanding of the evolution of regeneration, and its relation to embryogenesis, therefore remains limited. Using beta-catenin as a marker, we investigated the role of canonical Wnt signaling during both regeneration and embryogenesis in the cnidarian Nematostella vectensis. The canonical Wnt signaling pathway is known to play a conserved role in primary axis patterning in triploblasts. Induction of Wnt signaling with alsterpaullone results in ectopic oral tissue during both regeneration and embryogenesis by specifically upregulating beta-catenin expression, as measured by qRTPCR. Our data indicate that canonical Wnt signaling is sufficient for oral patterning during Nematostella regeneration and embryogenesis. These data also contribute to a growing body of literature indicating a conserved role for patterning mechanisms across various developmental modes of metazoans. PMID- 22052822 TI - Human serum albumin nanotubes with esterase activity. AB - A nanocylindrical wall structure was obtained by layer-by-layer (LbL) assembly of poly-L-arginine (PLA) and human serum albumin (HSA) and characterized by scanning electron microscopy (SEM), scanning force microscopy (SFM), and cryogenic transmission electron microscopy (cryo-TEM). SEM and SFM measurements of a lyophilized powder of (PLA/HSA)(3) nanotubes yielded images of round, chimney like architectures with approximately 100 nm wall thickness. Cryo-TEM images of the hydrated sample revealed that the tube walls are composed of densely packed HSA molecules. Moreover, when small-angle X-ray scattering was used to characterize the individual PLA and HSA components in aqueous solutions, maximum diameters of approximately 28 nm and 8 nm were obtained, respectively. These values indicate the minimum thickness of wall layers consisting of PLA and HSA. It can also be concluded from SEM as well as from cryo-TEM images that the protein cylinders are considerably swollen in the presence of water. Furthermore, HSA retains esterase activity if assembled in nanotubes, as indicated by measurements of para-nitrophenyl acetate hydrolysis under semi-physiological conditions (pH 7.4, 22 degrees C). The enzyme activity parameters (Michaelis constant, K(m), and catalytic constant, k(cat)) were comparable to those of free HSA. PMID- 22052823 TI - The multivalent effect in glycosidase inhibition: probing the influence of architectural parameters with cyclodextrin-based iminosugar click clusters. AB - In contrast to most lectins, glycosidases may appear to be unpromising targets for multivalent binding because they display only a single active site. To explore the potential of multivalency on glycosidase inhibition, unprecedented cyclodextrin-based iminosugar conjugates have been designed and prepared. The synthesis was performed by way of Cu(I) -catalyzed azide-alkyne cycloaddition reaction under microwave activation between propargylated multivalent beta cyclodextrins and an azide-armed N-alkyl 1-deoxynojirimycin derivative. Evaluation with a panel of glycosidases of this new class of glycomimetic clusters revealed the strongest affinity enhancement observed to date for a multivalent glycosidase inhibitor, with binding enhancement up to four orders of magnitude over the corresponding monovalent ligand for alpha-mannosidase. These results demonstrate that the multivalency concept extends beyond carbohydrate lectin recognition processes to glycomimetic-enzyme inhibition. PMID- 22052824 TI - Using baicalin-functionalized magnetic nanoparticles for selectively extracting flavonoids from Rosa chinensis. AB - An extraction agent featuring a natural product, baicalin, anchored on the surface of nanomagnetic particles (BMNPs) is herein reported. A facile solid phase extraction (SPE) procedure with high selectivity toward flavonoids using BMNPs has been established. BMNPs were proven very effective for enriching flavonoids from extracts of medicinal plants such as Rosa chinensis. The SPE protocol involving a convenient solid-liquid separation by using an external magnet field was easy to carry out. Further, the SPE sorbent (BMNPs) could be reused for many times reducing the operation cost. Importantly, flavonoids retained on the BMNPs were effectively recovered by eluting with methanol. Coupling the proposed SPE with ESI-MS/MS allowed a quick quantification of flavonoids in herbal extracts. Simultaneous determination of eight flavonoids extracted from R. chinensis was demonstrated in this work. PMID- 22052825 TI - Effect of introducing a short amyloidogenic sequence from the Abeta peptide at the N-terminus of 18-residue amphipathic helical peptides. AB - Fibril formation is the hallmark of pathogenesis in Alzheimer's disease and other amyloid disorders caused by conformational alterations leading to the aggregation of soluble monomers. Abeta40 self-associates to form amyloid fibrils. Its central seven-residue segment KLVFFAE (Abeta16-22), which is thought to be crucial for fibril formation of the full-length peptide, forms fibrils even in isolation. Context-dependent induction of amyloid formation by such sequences in peptides, which otherwise do not have that propensity, is of considerable interest. We have examined the effect of introducing the Abeta16-22 sequence at the N-terminus of two amphipathic helical 18-residue peptides Ac-WYSEMKRNVQRLERAIEE-am and Ac KQLIRFLKRLDRNLWGLA-am, which have high average hydrophobic moment values but have net charges of 0 and +4, respectively, at neutral pH. Upon incubation in aqueous buffer, fibril-like aggregates were discernible by transmission electron microscopy for the peptide with only 0 net charge, which also displayed ThT binding and beta-structure. Although both the sequences have been derived from amphipathic helical segments in globular proteins and possess high average hydrophobic moments, the +4 charge peptide lacks the ability to form fibrils, while the peptide with 0 charge has the tendency to form fibrillar structures. Variation in the net charge and the presence of several glutamic acids in the sequence of the peptide with net charge 0 appear to favor the formation of fibrils when the Abeta16-22 sequence is attached at the N-terminus. PMID- 22052826 TI - Advances in the management of recurrent or metastatic squamous cell carcinoma of the head and neck. AB - Most patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) undergo definitive therapy, yet locoregional recurrence and metastasis are common. Most patients ultimately require systemic treatment. Platinum/5 fluorouracil (5-FU) has been the standard of care for patients with good performance status (median survival, 6-8 months). Cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), significantly improved median survival in combination with platinum/5-FU compared with chemotherapy alone, establishing it as a new standard for patients with recurrent or metastatic disease. Cetuximab is also active in platinum-refractory disease. Ongoing trials are exploring other EGFR inhibitors as well as the use of biologic agents in combination (eg, cetuximab + bevacizumab). Predictive biomarkers may help personalize therapy for SCCHN, and it is unclear whether the favorable prognostic effect of p16 or human papillomavirus in locally advanced oropharyngeal cancer is relevant for advanced disease. PMID- 22052827 TI - Organometallic complexes in supported ionic-liquid phase (SILP) catalysts: a PHIP NMR spectroscopy study. AB - para-Hydrogen induced polarization (PHIP) NMR spectroscopy emerges as an efficient and robust method for on-line monitoring of gas-phase hydrogenation reactions. Here we report detailed investigations of supported ionic liquid phase (SILP) catalysts in a continuous gas-phase hydrogenation of propene with PHIP NMR spectroscopy. A relocation of the rhodium complex in the thin layer of ionic liquid in the SILP catalyst at the initial stage of the propene hydrogenation is demonstrated. PHIP NMR spectroscopy can provide profound insight into the evolution of SILP catalysts during hydrogenation reactions. PMID- 22052828 TI - Superconductivity and ferromagnetism in EuFe2(As(1-x)P(x))2. AB - Superconductivity and ferromagnetism are two antagonistic cooperative phenomena, which makes it difficult for them to coexist. Here we demonstrate experimentally that they do coexist in EuFe2(As(1-x)P(x))2 with 0.2 <= x <= 0.4, in which superconductivity is associated with Fe 3d electrons and ferromagnetism comes from the long-range ordering of Eu 4f moments via Ruderman-Kittel-Kasuya-Yosida (RKKY) interactions. The coexistence features large saturated ferromagnetic moments, high and comparable superconducting and magnetic transition temperatures, and broad coexistence ranges in temperature and field. We ascribe this unusual phenomenon to the robustness of superconductivity as well as the multi-orbital character of iron pnictides. PMID- 22052829 TI - Initial testing (stage 1) of SGI-1776, a PIM1 kinase inhibitor, by the pediatric preclinical testing program. AB - The PIM kinase inhibitor, SGI-1776, was tested against the PPTP in vitro (1.0 nM 10 uM) and in vivo panels (148 mg/kg daily * 5 days for 3 weeks). SGI-1776 exhibited cytotoxic activity in vitro with a median relative IC(50) of 3.1 uM. SGI-1776 induced significant differences in EFS distribution in vivo in 9 of 31 solid tumor xenografts and in 1 of 8 of the evaluable ALL xenografts. SGI-1776 induced tumor growth inhibition meeting criteria for intermediate EFS T/C activity in 1 of 39 evaluable models. In contrast, SGI-1776 induced complete responses of subcutaneous MV4;11 (B myeloid leukemia). PMID- 22052830 TI - Objective assessment of nasality in Flemish adults with neurofibromatosis type 1. AB - When characterizing the speech of a patient with neurofibromatosis type 1 (NF1), hypernasality is often mentioned. As few studies applied technically assisted evaluations of nasality in NF1 patients, the aim of the present study was to document the nasal resonance of adults with NF1 using nasometry. The nasometric data obtained from the NF1 patients were compared with the nasalance scores of a healthy control group and with normative data. The final study group consisted of 24 adult NF1 patients and 16 controls, all living in the East Flemish part of Belgium. Nasalance scores were obtained while the participants sustained three vowels (/a:/, /i./, and /u./) and one consonant (/m/) and read three standard nasalance passages. Despite the inter- and intra-subject variability, we observed that NF1 patients as a group exhibited higher mean nasalance scores than controls. This finding was especially clear in males. Potential genotype phenotype correlations between NF1 mutation type and hypernasality were examined but could not be demonstrated. Conversely, comparison of the nasometric data obtained from the NF1 patients with magnetic resonance imaging findings showed some degree of interesting correlation. We conclude that, notwithstanding the small sample size for some analyses, nasality is an area of interest in the NF1 population. As altered nasality influences speech intelligibility, nasality requires attention during follow-up visits, particularly when it concerns a male NF1 patient. PMID- 22052831 TI - Accurate bond energies of hydrocarbons from complete basis set extrapolated multi reference singles and doubles configuration interaction. AB - Quantum chemistry has become one of the most reliable tools for characterizing the thermochemical underpinnings of reactions, such as bond dissociation energies (BDEs). The accurate prediction of these particular properties (BDEs) are challenging for ab initio methods based on perturbative corrections or coupled cluster expansions of the single-determinant Hartree-Fock wave function: the processes of bond breaking and forming are inherently multi-configurational and require an accurate description of non-dynamical electron correlation. To this end, we present a systematic ab initio approach for computing BDEs that is based on three components: 1) multi-reference single and double excitation configuration interaction (MRSDCI) for the electronic energies; 2) a two parameter scheme for extrapolating MRSDCI energies to the complete basis set limit; and 3) DFT-B3LYP calculations of minimum-energy structures and vibrational frequencies to account for zero point energy and thermal corrections. We validated our methodology against a set of reliable experimental BDE values of C?C and C?H bonds of hydrocarbons. The goal of chemical accuracy is achieved, on average, without applying any empirical corrections to the MRSDCI electronic energies. We then use this composite scheme to make predictions of BDEs in a large number of hydrocarbon molecules for which there are no experimental data, so as to provide needed thermochemical estimates for fuel molecules. PMID- 22052833 TI - A comparison of methods using optical coherence tomography to detect demineralized regions in teeth. AB - Optical coherence tomography (OCT) is a three- dimensional optical imaging technique that can be used to identify areas of early caries formation in dental enamel. The OCT signal at 850 nm back-reflected from sound enamel is attenuated stronger than the signal back-reflected from demineralized regions. To quantify this observation, the OCT signal as a function of depth into the enamel (also known as the A-scan intensity), the histogram of the A-scan intensities and three summary parameters derived from the A-scan are defined and their diagnostic potential compared. A total of 754 OCT A-scans were analyzed. The three summary parameters derived from the A-scans, the OCT attenuation coefficient as well as the mean and standard deviation of the lognormal fit to the histogram of the A scan ensemble show statistically significant differences (p < 0.01) when comparing parameters from sound enamel and caries. Furthermore, these parameters only show a modest correlation. Based on the area under the curve (AUC) of the receiver operating characteristics (ROC) plot, the OCT attenuation coefficient shows higher discriminatory capacity (AUC = 0.98) compared to the parameters derived from the lognormal fit to the histogram of the A-scan. However, direct analysis of the A-scans or the histogram of A-scan intensities using linear support vector machine classification shows diagnostic discrimination (AUC = 0.96) comparable to that achieved using the attenuation coefficient. These findings suggest that either direct analysis of the A-scan, its intensity histogram or the attenuation coefficient derived from the descending slope of the OCT A-scan have high capacity to discriminate between regions of caries and sound enamel. PMID- 22052836 TI - Molecularly imprinted supermacroporous cryogels for cytochrome c recognition. AB - Molecular imprinting is an attractive biomimetic approach that creates specific recognition sites for the shape and functional group arrangement to template molecules. The purpose of this study is to prepare cytochrome c-imprinted poly(hydroxyethyl methacrylate) (PHEMA)-based supermacroporous cryogel which can be used for the separation of cytochrome c from protein mixtures. N-Methacryloyl (L)-histidinemethylester (MAH) was used as the metal-coordinating monomer. In the first step, Cu(2+) was complexed with MAH, and the cytochrome c imprinted PHEMA (MIP) cryogel was prepared by free radical cryopolymerization initiated by N,N,N',N'-tetramethylene diamine at -12 degrees C. After polymerization is completed, the template cytochrome c molecules were removed from the MIP cryogel using 0.5 M NaCl solution. The maximum cytochrome c binding amount was 126 mg/g polymer. Selective binding studies were performed in the presence of lysozyme and bovine serum albumin. The relative selectivity coefficients of MIP cryogel for cytochrome c/lysozyme and cytochrome c/bovine serum albumin were 1.7 and 5.2 times greater than those of the non-imprinted PHEMA cryogel, respectively. The selectivity of MIP cryogel for cytochrome c was also confirmed with fast protein liquid chromatography. The MIP cryogel could be used many times with no remarkable decrease in cytochrome c binding capacity. PMID- 22052837 TI - First solid-state structures of real diorganyl phosphinous acids R2POH (R=CF3, C2F5). PMID- 22052838 TI - The solution structure of the S4-S5 linker of the hERG potassium channel. AB - The human ether-a-go-go related gene (hERG) encodes a protein that forms a voltage-gated potassium channel and plays an important role in the heart by controlling the rapid delayed rectifier K(+) current (I(Kr)). The S4-S5 linker was shown to be important for the gating of the hERG channel. Nuclear magnetic resonance study showed that a peptide derived from the S4-S5 linker had no well ordered structure in aqueous solution and adopted a 3(10) -helix (E544-Y545-G546) structure in detergent micelles. The existence of an amphipathic helix was confirmed, which may be important for interaction with cell membrane. Close contact between side chains of residues R541 and E544 was observed, which may be important for its regulation of channel gating. PMID- 22052839 TI - Significant association of SRC protein expression with the progression, recurrence, and prognosis of oral squamous cell carcinoma in Taiwan. AB - BACKGROUND: Src protein overexpression correlates with progression and prognosis of a variety of human cancers. METHODS: This study used immunohistochemistry to examine the expression of Src protein in 93 specimens of oral squamous cell carcinoma (OSCC). RESULTS: We found a significant association of high expression of Src protein (labeling indices >50%) with larger tumor size (p = .017), positive lymph node metastasis (p = .030), more advanced clinical stages (p = .007), and recurrence (p < .001) of OSCC. High expression of Src protein was identified as an independent unfavorable prognosis factor by multivariate Cox regression analysis. The Kaplan-Meier curve showed that patients with OSCC with high expression of Src protein had a significantly poorer cumulative survival than those with low expression of Src protein (log-rank test, p = .00267). CONCLUSION: The expression of Src protein is significantly associated with the progression, recurrence, and prognosis of OSCCs in Taiwan. PMID- 22052840 TI - Red-emitting dyes with photophysical and photochemical properties controlled by pH. AB - New unsymmetrical zinc azaphthalocyanines, bearing one substituted aniline as a peripheral substituent, were prepared by using a statistical condensation approach. Both fluorescence and singlet oxygen quantum yields were extremely low in DMF (Phi(F)<0.01, Phi(Delta)<0.02, respectively), but increased after the addition of sulfuric acid, reaching values comparable to controls without aniline substituents (Phi(F)=0.22-0.29, Phi(Delta)=0.40-0.59, respectively). This behavior was attributed to the deactivation of excited states by intramolecular charge transfer from a donor site (aniline), which was blocked after protonation in acidic media. In the protonated form, all of the compounds efficiently emitted light with lambda(em) in the region of 662-675 nm. The investigated compounds were anchored to dioleoylphosphatidylcholine (DOPC) unilamellar vesicles and showed response to buffer pH. They were highly fluorescent at low pH values and almost nonfluorescent in neutral solutions. The pK(a) values were determined in DOPC vesicles and ranged between 2.2 and 4.2. PMID- 22052841 TI - Inhomogeneous superconductivity in organic conductors: the role of disorder and magnetic field. AB - Several experimental studies have shown the presence of spatially inhomogeneous phase coexistence of superconducting and non-superconducting domains in low dimensional organic superconductors. The superconducting properties of these systems are found to be strongly dependent on the amount of disorder introduced in the sample regardless of its origin. The suppression of the superconducting transition temperature T(c) shows a clear discrepancy with the result expected from the Abrikosov-Gor'kov law giving the behavior of T(c) with impurities. On the basis of the time dependent Ginzburg-Landau theory, we derive a model to account for this striking feature of T(c) in organic superconductors for different types of disorder by considering the segregated texture of the system. We show that the calculated T(c) quantitatively agrees with experiments. We also focus on the effect of superconducting fluctuations on the upper critical fields H(c2) of layered superconductors showing slab structure where superconducting domains are sandwiched by non-superconducting regions. We found that H(c2) may be strongly enhanced by such fluctuations. PMID- 22052842 TI - Diagnostic delay in pediatric solid tumors: a population based study on determinants and impact on outcomes. AB - BACKGROUND: Despite socioeconomic and clinical progress, pediatric tumors continue to present in advanced stage, and may be due to delays in diagnosis. This study aimed to identify factors associated with diagnostic delay (time between symptom onset and diagnosis) in pediatric tumors in a population-based study, and to assess the impact of delay on subsequent outcome. PROCEDURE: Natural logarithm of delay was retrospectively described for 390 newly diagnosed tumors reported to the Singapore Childhood Cancer Registry from 1997 to 2007. Delay was correlated with socio-demographic, disease and healthcare-system factors using multivariate linear regression, and with event-free survival (EFS) using Cox regression analysis. RESULTS: Total median delay was 5.3 weeks (range 0.1-283.1). Shorter delay was independently associated with younger patient age (P = 0.006), abdominal and pelvic sites (P < 0.001 and P = 0.036, respectively), incidental diagnoses by healthcare staff (P = 0.002), and when pediatric emergency units were the first contacted healthcare facilities and the first to raise suspicion of malignancy (P = 0.034, and P = 0.018, respectively). These factors explained only a small percentage of variance in delay times (21%). Delay was not associated with EFS and disease stage, with 24% of tumors presenting in stage 4. CONCLUSIONS: Diagnostic delay was independently associated with age and site of presentation, and points of first symptom detection, first healthcare contact, and first suspicion of malignancy. The broad range of clinical variables analyzed could only account in a small way for differences in delay times observed. While overall delay times were short, they did not influence disease stage at presentation and eventual outcome. PMID- 22052843 TI - Mosaic marker chromosome 16 resulting in 16q11.2-q12.1 gain in a child with intellectual disability, microcephaly, and cerebellar cortical dysplasia. AB - Proximal duplications of the long arm of chromosome 16 are rare and only a few patients have been reported. Clinically, the patients do not have a distinctive syndromic appearance; however they all show some degree of intellectual disability and most have severely delayed speech development. We report on a child presenting with mild-to-moderate intellectual disability, microcephaly, language dyspraxia, and mild dysmorphisms who was found to have a mosaic gain of chromosome 16q (16q11.2-16q12.1). Magnetic resonance imaging done at the age of 4 years demonstrated cerebellar cortical dysplasia involving the vermis and hemispheres. This is the first report of cerebellar anomalies in a patient with partial trisomy 16q. The genes ZNF423 and CBLN1 found in the duplicated region play a role in the development of the cerebellum and may be responsible for the cerebellar cortical dysplasia. PMID- 22052844 TI - Changes in fluorescent emission due to non-covalent interactions as a general detection procedure for thin-layer chromatography. AB - Changes in fluorescence emission due to non-covalent analyte-fluorophore interactions in silica gel plates are studied and used as a general detection procedure for thin-layer chromatography (TLC). The presence of the analyte modifies the microenvironment of the fluorophore and thus changes the balance between radiative (k(r)) and non-radiative (k(nr)) emission constants. A model is proposed for analyte-fluorophore induced electrostatic interactions, which depend on analyte polarizability and are responsible for fluorescence enhancements. As consequence of these induced interactions, the analyte creates an apolar environment that prevents non-fluorescent decay mechanisms, decreasing k(nr). On the other hand, the effect of an increase in refractive index on k(r) is investigated, as it contributes to some extent to fluorescence enhancements in silica gel medium. Changes in fluorescence emission should be regarded as a general property of fluorophores in the presence of analytes, and criteria that fluorophores should meet to be used as sensitive TLC probes are discussed here. PMID- 22052846 TI - Flow perfusion maintains ex vivo bone viability: a novel model for bone biology research. AB - Encased in lacunae, osteocytes receive nutrition and biomechanical signals through the lacunocanalicular system. We have developed a novel flow-perfusion bioreactor designed to support lacunocanalicular fluid flow. We hypothesize that ex vivo fluid flow can maintain endochondral bone viability and, ultimately, serve as a novel model to study bone biology in vitro. Sprague-Dawley rat femurs were harvested, stripped of soft tissue, loaded into a custom-designed bioreactor and perfused with osteogenic culture medium. After 14 days of flow-perfusion or static culture, the bones were harvested, fixed, decalcified, embedded, sectioned and stained with haematoxylin and eosin. Fresh long bone samples were similarly processed for comparison. Osteocyte viability and function were also evaluated, using thiazolyl blue tetrazolium bromide (MTT), fluorospectrophotometric DNA quantification, alkaline phosphatase (ALP) colorimetric assay and fluorochrome labelling of mineralizing surfaces. All samples remained free of infection throughout the study period. After 14 days of flow perfusion, histological analysis showed normal-appearing bony architecture, with 72% of lacunae being osteocyte-filled compared with 93% in freshly harvested samples and only 36% in static samples. MTT staining and assay confirmed osteocyte viability in the flow perfusion samples as well as in fresh samples. DNA quantification demonstrated DNA to be preserved in flow-perfused samples when compared with freshly harvested samples. ALP activity in flow-perfusion explants was upregulated compared with fresh and static samples. Fluorochrome-labelled mineralizing surfaces were seen throughout the explanted flow-perfused samples. This is the first demonstration that flow perfusion provides adequate chemotransportation to explanted murine endochondal bones. PMID- 22052845 TI - Preparation, characterization and application of a new stir bar sorptive extraction based on poly(vinylphthalimide-co-N,N'-methylenebisacrylamide) monolith. AB - In this study, a new stir bar sorptive extraction (SBSE) coating based on poly(vinylphthalimide-co-N,N'-methylenebisacrylamide) monolith (SBSE-VPMB) was prepared. The influences of the contents of monomer in polymerization mixture and the percentage of porogen solvent on the extraction performance were investigated thoroughly. Several characteristic techniques, such as elemental analysis, scanning electron microscopy, mercury intrusion porosimetry and infrared spectroscopy, were used to characterize the monolithic material. The analysis of oxfendazole (OFZ) and mebendazole (MBZ) in milk and honey samples by the combination of SBSE with HPLC with diode array detection was selected as paradigms for the practical evaluation of the new coating. Under the optimized extraction conditions, the limits of detection (S/N=3) for OFZ and MBZ were 0.23 0.60 MUg/L in milk and 0.24-1.08 MUg/L in honey, respectively. The method also showed good linearity, repeatability, high feasibility and acceptable recoveries for real samples. At the same time, the extraction performance and the distribution coefficients (K(VPMB/W)) of OFZ and MBZ on SBSE-VPMB were compared with other SBSEs based on porous monoliths and commercial SBSE. PMID- 22052847 TI - The synthesis of a new class of chiral pincer ligands and their applications in enantioselective catalytic fluorinations and the Nozaki-Hiyama-Kishi reaction. AB - A new class of chiral tridentate N-donor pincer ligands, bis(oxazolinylmethylidene)isoindolines (boxmi), was synthesized in three steps starting from readily available phthalimides. Their reaction with ethyl (triphenylphosphoranylidene)acetate by means of a key-step Wittig reaction gave the ligand backbones, which were condensed with amino alcohols and then cyclized to obtain the corresponding ligands. These ligands were subsequently applied in the nickel(II)-catalyzed enantioselective fluorination of oxindoles and beta ketoesters to obtain the corresponding products with enantioselectivities of up to >99% ee and high yields. Application of the chiral pincer ligands in the chromium-catalyzed enantioselective Nozaki-Hiyama-Kishi reaction of aldehydes gave the corresponding alcohols with an optimal enantioselectivity of 93%. PMID- 22052848 TI - Self-healing of chemical gels cross-linked by diarylbibenzofuranone-based trigger free dynamic covalent bonds at room temperature. PMID- 22052849 TI - Surfactant induced symmetric and thermally stable interfaces in Cu/Co multilayers. AB - In this work we studied Ag surfactant induced growth of Cu/Co multilayers. The Cu/Co multilayers were deposited using Ag surfactant by the ion beam sputtering technique. It was found that Ag surfactant balances the asymmetry between the surface free energies of Cu and Co. As a result, the Co-on-Cu and Cu-on-Co interfaces become sharp and symmetric and thereby improve the thermal stability of the multilayer. On the basis of obtained results, a mechanism leading to symmetric and stable interfaces in Cu/Co multilayers is discussed. PMID- 22052850 TI - Imatinib has adverse effect on growth in children with chronic myeloid leukemia. AB - BACKGROUND: Long-term adverse effects of Imatinib in children with chronic myeloid leukemia (CML) are uncertain. The aim was to study the effect of imatinib on growth in children with CML. PROCEDURE: Children <=13 years of age at diagnosis were enrolled retrospectively, from 2004 to 2011, from a single center in India. Patients who received imatinib for >1 year were included for growth assessment. Height standard deviation scores (SDS) were derived from WHO AnthroPlus, a global growth monitoring tool. RESULTS: Thirty-four children received imatinib. Twenty children fulfilled the criteria for assessment of growth. Median age was 10 years (range: 2-13). Of 20 children, 13 were prepubertal at commencement of imatinib. The mean duration of imatinib in 20 children was 61.3 +/- 16.2 months (range: 31-83). No patient was treated with a second-generation tyrosine kinase inhibitor or a stem cell transplant. Highly significant reduction in height SDS's was observed (P = 0.002 at 5th year). Children who started imatinib therapy after the onset of puberty were immune to this adverse effect (P = 0.448 and 0.003 at 5th year of treatment for pubertal and prepubertal children, respectively). The 5-year survival probability of 33 children who received imatinib in chronic phase was 80% with a median survival time of 60 months (mean: 70.2; 95% CI: 60-80.5). CONCLUSIONS: Growth retardation is a significant adverse effect of imatinib in children with CML. The failure to gain appropriate height was most discernible when imatinib was initiated in the prepubertal period. Etiology and remedial measures need to be investigated. PMID- 22052851 TI - Severe neonatal-onset panniculitis in a female infant with Prader-Willi syndrome. AB - The panniculitides are a group of heterogeneous inflammatory diseases involving the subcutaneous fat, the pathogenesis of which is poorly understood. Here, we report on a female infant with Prader-Willi syndrome who developed a systemic inflammatory disorder in the neonatal period demonstrating recurrent panniculitis as a prominent feature. This is the second report of an association between Prader-Willi syndrome and panniculitis. Such an association might be explained by the unmasking of a recessive allele as a consequence of hemizygosity, in the case of a 15q11 deletion, or homozygosity, in the case of maternal isodisomy. PMID- 22052852 TI - Theoretical study of the Raman optical activity spectra of 3(10)-helical polypeptides. AB - Raman optical activity (ROA) spectroscopy is a promising analytical method for studying the structure and conformation of polypeptides and proteins in solution. However, the structural information obtained from such vibrational spectra is only indirect and theoretical studies are often necessary to identify how the structure determines the observed spectra. One particular target is the identification and discrimination of different helical secondary structure elements. Herein, a theoretical investigation of the ROA spectra of a series of 3(10)-helical polypeptides is presented. In particular, the effect of chain length, C(alpha)-substitution pattern, the introduction of larger aliphatic side chains, and the variation of their conformation on the ROA spectra is studied. To extract general principles from these calculations, the positions, intensities, and shapes of the ROA bands are analyzed in terms of localized modes, which makes it possible to identify possible ROA signatures of 3(10) -helical structures, but also provides fundamental insight into the generation of ROA signals in complex polypeptides. Finally, the calculated spectra can be compared to the previously reported ROA spectrum of a specifically designed 3(10) -helical heptapeptide. This allows most of the features in the experimental spectrum to be assigned. PMID- 22052853 TI - Self-assembly of renal cells into engineered renal tissues in collagen/Matrigel scaffold in vitro. AB - To tissue engineer a kidney is a formidable task because of the complex cell composition and structures in the kidney. This study reconstructed renal tissues using mixed renal cells in collagen/Matrigel(r) scaffolds in vitro. Neonatal rat renal cells were seeded in collagen I supplemented with Matrigel in a casting mold that could exert static stretch when the renal constructs contracted. During in vitro culture, the renal constructs were observed under microscope and analyzed by histological and immunofluorescent examinations. Results showed that the mixed renal cells reconstituted renal tubular and glomeruli-like structures with different appearances at varying developmental stages. Tubular structures were formed by CK18-positive cells with similar appearances lining the surrounding hollow centres. The glomeruli-like structures were tufts of cell aggregates containing Flk-1-positive cells. These results show that neonatal rat renal cells self-assembled into engineered renal tissues containing both tubules and glomeruli-like structures when cultured in 3D collagen/Matrigel scaffold in vitro. PMID- 22052854 TI - Role of insulin-like growth factor-II mRNA-binding protein-3 in invadopodia formation and the growth of oral squamous cell carcinoma in athymic nude mice. AB - BACKGROUND: The invadopodia are specialized structures that degrade the extracellular matrix (ECM) and promote cell invasion and metastasis. Understanding the forms and functions of invadopodia should facilitate the proper identification of novel targets for antiinvasive therapy. METHODS: To understand the role of insulin-like growth factor-II mRNA-binding protein-3 (IMP-3) in invadopodia formation and cancer invasion, we performed IMP-3 gene silencing, invadopodia formation, ECM degradation assay, zymography, western blot, and mouse xenograft. RESULTS: We demonstrate that invadopodia evidenced ECM degradation activity in oral squamous cell carcinoma (OSCC). Downregulation of IMP-3 inhibited invadopodia formation, ECM degradation, and tumor growth and invasiveness. Epidermal growth factor receptor (EGFR) signaling may perform a critical function in invadopodia formation, ECM degradation, IMP-3, and cortactin expression. CONCLUSION: IMP-3 may be intimately correlated with cancer invasion through invadopodia in oral cancer. The overexpression of IMP-3 in oral cancer was predictive of a high correlation with cancer growth and invasion. PMID- 22052855 TI - Exercise training mitigates anthracycline-induced chronic cardiotoxicity in a juvenile rat model. AB - BACKGROUND: Childhood cancer survivors are at greater risk of cardiovascular complications once they reach adulthood. Anthracyclines may be a major contributor to these delayed-onset complications, yet their use continues because of favorable clinical outcomes. Exercise has been shown to protect against anthracycline cardiotoxicity, yet it is unclear whether exercise can protect against delayed-onset cardiotoxicity when treatment is initiated in childhood. The aim of the present study was to determine if exercise training provides cardioprotection in a juvenile rat model of delayed-onset anthracycline cardiotoxicity. PROCEDURE: At 25 days of age, male Sprague-Dawley rat pups were subjected to a treatment regimen with the anthracycline doxorubicin (DOX). Pups received DOX at 2 mg/kg on 7 consecutive days (cumulative dose 14 mg/kg) or saline as a control. At the time DOX treatment began, pups remained sedentary or were allowed to voluntarily exercise. Ten weeks after the initiation of exercise, cardiac function was assessed both in vivo and ex vivo. RESULTS: DOX treatment stunted normal growth and significantly impaired cardiac function. While voluntary exercise did not offset changes in the growth curve, it did provide significant cardioprotection against DOX-induced cardiotoxicity. CONCLUSIONS: Exercise training, initiated at the time treatment begins, can protect against delayed-onset anthracycline-induced cardiotoxicity in adult rats that were treated with anthracyclines as juveniles. PMID- 22052856 TI - Compound heterozygous mutations in PYCR1 further expand the phenotypic spectrum of De Barsy syndrome. AB - De Barsy syndrome (DBS) is characterized by progeroid features, ophthalmological abnormalities, intrauterine growth retardation, and cutis laxa. Recently, PYCR1 mutations were identified in cutis laxa with progeroid features. Herein, we report on a DBS patient born to a nonconsanguineous Chinese family. The exceptional observation of congenital glaucoma, aortic root dilatation, and idiopathic hypertrophic pyloric stenosis in this patient widened the range of symptoms that have been noted in DBS. Mutation analysis of PYCR1 revealed compound heterozygous PYCR1 mutations, including a p.P115fsX7 null mutation allele and a second allele with two missense mutations in cis: p.G248E and p.G297R. The effect of mutation results in a reduction of PYCR1 mRNA expression and PYCR1 protein expression in skin fibroblasts from the patient. The findings presented here suggest a mutation screening of PYCR1 and cardiovascular survey in patients with DBS. PMID- 22052857 TI - Flux of selected body fluid constituents and benzylpenicillin in polyacrylamide hydrogel (PAAG). AB - The polyacrylamide hydrogel (PAAG) Aquamid(r) (Contura International A/S Soeborg, Denmark) is one of the new macromolecules that are used as implants and tissue fillers in reconstruction and aesthetic surgery. This study showed, by means of radioactive isotope methods, that PAAG can exchange both physiological and non physiological constituents very efficiently with the surrounding medium. The efflux (J, mole/(cm(2)* s), 25 degrees C, pH 7.2) of water (4.4 * 10(-5) ), chloride (2.4 * 10(-7) ), urea (1.0 * 10(-9) ), and glucose (1.1 * 10(-9) ) was 3 40x greater than in human red blood cells. PAAG was also accessible to sucrose, inulin, and benzylpenicillin that could not permeate biological cell membranes. The conclusion of the study is that the hydrogel structure created no significant barrier to the exchange of solvent and solutes with the surrounding medium. PMID- 22052860 TI - Treatment of pharyngeal non-Hodgkin lymphoma in a patient with Wiskott-Aldrich syndrome. AB - Wiskott-Aldrich syndrome (WAS) is characterized by primary immunodeficiency, thrombocytopenia and eczema. Patients with WAS have an increased risk to develop tumors. Non-Hodgkin lymphoma (NHL) represents the most common malignancy occurring in WAS-affected patients, diffuse-large-B-cell lymphoma is the most frequently encountered variant. We describe a case of a patient with WAS and NHL in the pharynx, an atypical tumor site presentation. The patient was successfully treated with a reduced dose chemotherapy regimen plus anti-CD20 monoclonal antibody. He is in complete remission 3 years from the start of treatment. PMID- 22052861 TI - Rhizomelic chondrodysplasia punctata type 1 and fulminant neonatal respiratory failure, a case report and discussion of pathophysiology. PMID- 22052862 TI - The effects of fibrin and fibrin-agarose on the extracellular matrix profile of bioengineered oral mucosa. AB - Several studies have developed efficient oral mucosa constructs using different types of scaffold. However, the changes in the morphology and gene and protein expression profile that could occur in these artificial constructs remain unknown. This study compared the histology and expression of several extracellular matrix molecules in human artificial oral mucosa developed using two different types of scaffolds: fibrin and fibrin-agarose. To that end, bioengineered oral mucosa stromas were constructed from biopsy samples of human oral mucosa and the substitute generated was analyzed at different periods of time in culture. Histological analysis was carried out by light and transmission electron microscopy and the expression of collagen types I, III, and VI, the proteoglycans decorin and biglycan, and the different chains of laminin, were assessed by immunoperoxidase technique. This study found that fibrin scaffolds accelerated fibroblast growth and remodeling of the scaffold, thus enhancing collagen fibrillogenesis. In the fibrin-agarose scaffold, the morphology and organization of the fibroblasts did not change during the culture period. All extracellular matrix proteins analyzed were expressed in both scaffolds. However, in fibrin scaffolds, these proteins were widely distributed and replaced the scaffold during the follow-up period. These results show that the substitutes generated showed histological and molecular similarities with native human oral mucosa stroma. In addition, it was observed that the nature of the biomaterial influenced the behaviour of the oral stromal fibroblasts, thereby modulating their growth, protein synthesis, and collagen fibrillogenesis. PMID- 22052863 TI - Mental retardation or intellectual disability? Time for a change. PMID- 22052864 TI - In vivo formation of bone and haematopoietic territories by transplanted human bone marrow stromal cells generated in medium with and without osteogenic supplements. AB - Autologous transplantation of human bone marrow stromal cells (BMSCs) has been successfully used for bone reconstruction. However, in order to advance this approach into the mainstream of bone tissue engineering, the conditions for BMSC cultivation and transplantation must be optimized. In a recent report, cultivation with dexamethasone (Dex) significantly increased bone formation by human BMSCs in vivo. Based on this important conclusion, we analysed the data accumulated by our laboratory, where human BMSCs have been routinely generated using media both with and without a combination of two osteogenic supplements: Dex at 10(-8) m and ascorbic acid phosphate (AscP) at 10(-4) m. Our data demonstrate that for 22/24 donors, BMSC strains propagated with and without Dex/AscP formed similar amounts of bone in vivo. Thus, human BMSCs do not appear to need to be induced to osteogenic differentiation ex vivo prior to transplantation. Similarly, for 12/14 donors, BMSC strains cultured with and without Dex/AscP formed haematopoietic territories to a comparable extent. While Dex/AscP did not increase bone formation, they significantly stimulated BMSC in vitro proliferation without affecting the number of BMSC colonies formed by the colony-forming units-fibroblasts. We conclude that for the substantial majority of donors, Dex/AscP have no effect on the ability of BMSCs to form bone and myelosupportive stroma in vivo. However, due to increased BMSC proliferation, the total osteogenic population obtained from a single marrow sample is larger after cultivation with Dex/AscP than without them. Secondary to increased BMSC proliferation, Dex/AscP may stimulate bone formation if BMSCs and/or the transplantation system are less than optimal. Published 2011. This article is a U.S. Government work and is in the public domain in the USA. PMID- 22052866 TI - The rise of passive airway smooth muscle mechanics. PMID- 22052865 TI - Mild heat stress induces mitochondrial biogenesis in C2C12 myotubes. AB - During endurance exercise, most (~75%) of the energy derived from the oxidation of metabolic fuels and ATP hydrolysis of muscle contraction is liberated as heat, the accumulation of which leads to an increase in body temperature. For example, the temperature of exercising muscles can rise to 40 degrees C. Although severe heat injury can be deleterious, several beneficial effects of mild heat stress (HS), such as the improvement of insulin sensitivity in patients with type 2 diabetes, have been reported. However, among all cellular events induced by mild HS from physical activities, the direct effects and mechanisms of mild HS on mitochondrial biogenesis in skeletal muscle are least characterized. AMP activated protein kinase (AMPK) and sirtuin 1 (SIRT1) are key energy-sensing molecules regulating mitochondrial biogenesis. In C2C12 myotubes, we found that 1 h mild HS at 40 degrees C upregulated both AMPK activity and SIRT1 expression, as well as increased the expression of several mitochondrial biogenesis regulatory genes including peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) and transcription factors involved in mitochondrial biogenesis. In particular, PGC-1alpha expression was found to be transcriptionally regulated by mild HS. Additionally, after repeated mild HS for 5 days, protein levels of PGC-1alpha and several mitochondrial oxidative phosphorylation subunits were also upregulated. Repeated mild HS also significantly increased mitochondrial DNA copy number. In conclusion, these data show that mild HS is sufficient to induce mitochondrial biogenesis in C2C12 myotubes. Temperature-induced mitochondrial biogenesis correlates with activation of the AMPK-SIRT1-PGC-1alpha pathway. Therefore, it is possible that muscle heat production during exercise plays a role in mitochondrial biogenesis. PMID- 22052867 TI - Acute pantothenic acid and cysteine supplementation does not affect muscle coenzyme A content, fuel selection, or exercise performance in healthy humans. AB - Reduced skeletal muscle free coenzyme A (CoASH) availability may decrease the contribution of fat oxidation to ATP production during high-intensity, submaximal exercise or, alternatively, limit pyruvate dehydrogenase complex (PDC) flux and thereby carbohydrate oxidation. Here we attempted to increase the muscle CoASH pool in humans, via pantothenic acid and cysteine feeding, in order to elucidate the role of CoASH availability on muscle fuel metabolism during exercise. On three occasions, eight healthy male volunteers (age 22.9 +/- 1.4 yr, body mass index 24.2 +/- 1.5 kg/m(2)) cycled at 75% maximal oxygen uptake (Vo(2max)) to exhaustion, followed by a 15-min work output performance test. Muscle biopsies were obtained at rest, and after 60 min and 91.3 +/- 3.1 min of exercise (time to exhaustion on baseline visit) on each occasion. Two weeks following the first visit (baseline), 1 wk of oral supplementation with either 3 g/day of a placebo control (glucose polymer; CON) or 1.5 g/day each of d-pantothenic acid and l cysteine (CP) was carried out prior to the second and third visits in a randomized, counterbalanced, double-blind manner, leaving a 3-wk gap in total between each visit. Resting muscle CoASH content was not altered by supplementation in any visit. Following 60 min of exercise, muscle CoASH content was reduced by 13% from rest in all three visits (P < 0.05), and similar changes in the respiratory exchange ratio, glycogenolysis (~235 mmol/kg dry muscle), PCr degradation (~57 mmol/kg dry muscle), and lactate (~25 mmol/kg dry muscle) and acetylcarnitine (~12 mmol(.)kg/dry muscle) accumulation was observed during exercise when comparing visits. Furthermore, no difference in work output was observed when comparing CON and CP. Acute feeding with pantothenic acid and cysteine does not alter muscle CoASH content and consequently does not impact on muscle fuel metabolism or performance during exercise in humans. PMID- 22052868 TI - Phasic respiratory modulation of pharyngeal collapsibility via neuromuscular mechanisms in rats. AB - Obstructive sleep apnea patients experience recurrent upper airway (UA) collapse due to decreases in the UA dilator muscle activity during sleep. In contrast, activation of UA dilators reduces pharyngeal critical pressure (Pcrit, an index of pharyngeal collapsibility), suggesting an inverse relationship between pharyngeal collapsibility and dilator activity. Since most UA muscles display phasic respiratory activity, we hypothesized that pharyngeal collapsibility is modulated by respiratory drive via neuromuscular mechanisms. Adult male Sprague Dawley rats were anesthetized, vagotomized, and ventilated (normocapnia). In one group, integrated genioglossal activity, Pcrit, and maximal airflow (V(max)) were measured at three expiration and five inspiration time points within the breathing cycle. Pcrit was closely and inversely related to phasic genioglossal activity, with the value measured at peak inspiration being the lowest. In other groups, the variables were measured during expiration and peak inspiration, before and after each of five manipulations. Pcrit was 26% more negative (-15.0 +/- 1.0 cmH(2)O, -18.9 +/- 1.2 cmH(2)O; n = 23), V(max) was 7% larger (31.0 +/- 1.0 ml/s, 33.2 +/- 1.1 ml/s), nasal resistance was 12% bigger [0.49 +/- 0.05 cmH(2)O/(ml/s), 0.59 +/- 0.05 cmH(2)O/(ml/s)], and latency to induced UA closure was 14% longer (55 +/- 4 ms, 63 +/- 5 ms) during peak inspiration vs. expiration (all P < 0.005). The expiration-inspiration difference in Pcrit was abolished with neuromuscular blockade, hypocapnic apnea, or death but was not reduced by the superior laryngeal nerve transection or altered by tracheal displacement. Collectively, these results suggest that pharyngeal collapsibility is moment-by moment modulated by respiratory drive and this phasic modulation requires neuromuscular mechanisms, but not the UA negative pressure reflex or tracheal displacement by phasic lung inflation. PMID- 22052869 TI - Cerebral circulation during mild +Gz hypergravity by short-arm human centrifuge. AB - We examined changes in cerebral circulation in 15 healthy men during exposure to mild +Gz hypergravity (1.5 Gz, head-to-foot) using a short-arm centrifuge. Continuous arterial pressure waveform (tonometry), cerebral blood flow (CBF) velocity in the middle cerebral artery (transcranial Doppler ultrasonography), and partial pressure of end-tidal carbon dioxide (ETco(2)) were measured in the sitting position (1 Gz) and during 21 min of exposure to mild hypergravity (1.5 Gz). Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between beat-to-beat mean arterial pressure (MAP) and mean CBF velocity (MCBFV). Steady-state MAP did not change, but MCBFV was significantly reduced with 1.5 Gz (-7%). ETco(2) was also reduced (-12%). Variability of MAP increased significantly with 1.5 Gz in low (53%)- and high-frequency ranges (88%), but variability of MCBFV did not change in these frequency ranges, resulting in significant decreases in transfer function gain between MAP and MCBFV (gain in low-frequency range, -17%; gain in high-frequency range, -13%). In contrast, all of these indexes in the very low-frequency range were unchanged. Transfer from arterial pressure oscillations to CBF fluctuations was thus suppressed in low- and high-frequency ranges. These results suggest that steady state global CBF was reduced, but dynamic cerebral autoregulation in low- and high-frequency ranges was improved with stabilization of CBF fluctuations despite increases in arterial pressure oscillations during mild +Gz hypergravity. We speculate that this improvement in dynamic cerebral autoregulation within these frequency ranges may have been due to compensatory effects against the reduction in steady-state global CBF. PMID- 22052870 TI - The energetic cost of maintaining lateral balance during human running. AB - To quantify the energetic cost of maintaining lateral balance during human running, we provided external lateral stabilization (LS) while running with and without arm swing and measured changes in energetic cost and step width variability (indicator of lateral balance). We hypothesized that external LS would reduce energetic cost and step width variability of running (3.0 m/s), both with and without arm swing. We further hypothesized that the reduction in energetic cost and step width variability would be greater when running without arm swing compared with running with arm swing. We controlled for step width by having subjects run along a single line (zero target step width), which eliminated any interaction effects of step width and arm swing. We implemented a repeated-measures ANOVA with two within-subjects fixed factors (external LS and arm swing) to evaluate main and interaction effects. When provided with external LS (main effect), subjects reduced net metabolic power by 2.0% (P = 0.032) and step width variability by 12.3% (P = 0.005). Eliminating arm swing (main effect) increased net metabolic power by 7.6% (P < 0.001) but did not change step width variability (P = 0.975). We did not detect a significant interaction effect between external LS and arm swing. Thus, when comparing conditions of running with or without arm swing, external LS resulted in a similar reduction in net metabolic power and step width variability. We infer that the 2% reduction in the net energetic cost of running with external LS reflects the energetic cost of maintaining lateral balance. Furthermore, while eliminating arm swing increased the energetic cost of running overall, arm swing does not appear to assist with lateral balance. Our data suggest that humans use step width adjustments as the primary mechanism to maintain lateral balance during running. PMID- 22052871 TI - Inflammation in utero exacerbates ventilation-induced brain injury in preterm lambs. AB - Cerebral blood flow disturbance is a major contributor to brain injury in the preterm infant. The initiation of ventilation may be a critical time for cerebral hemodynamic disturbance leading to brain injury in preterm infants, particularly if they are exposed to inflammation in utero. We aimed to determine whether exposure to inflammation in utero alters cardiopulmonary hemodynamics, resulting in cerebral hemodynamic disturbance and related brain injury during the initiation of ventilation. Furthermore, we aimed to determine whether inflammation in utero alters the cerebral hemodynamic response to challenge induced by high mean airway pressures. Pregnant ewes received intra-amniotic lipopolysaccharide (LPS) or saline either 2 or 4-days before preterm delivery (at 128 +/- 1 days of gestation). Lambs were surgically instrumented for assessment of pulmonary and cerebral hemodynamics before delivery and positive pressure ventilation. After 30 min, lambs were challenged hemodynamically by incrementing and decrementing positive end-expiratory pressure. Blood gases, arterial pressures, and blood flows were recorded. The brain was collected for biochemical and histological assessment of inflammation, brain damage, vascular extravasation, hemorrhage, and oxidative injury. Carotid arterial pressure was higher and carotid blood flow was more variable in 2-day LPS lambs than in controls during the initial 15 min of ventilation. All lambs responded similarly to the hemodynamic challenge. Both 2- and 4-day LPS lambs had increased brain interleukin (IL)-1beta, IL-6, and IL-8 mRNA expression; increased number of inflammatory cells in the white matter; increased incidence and severity of brain damage; and vascular extravasation relative to controls. Microvascular hemorrhage was increased in 2-day LPS lambs compared with controls. Cerebral oxidative injury was not different between groups. Antenatal inflammation causes adverse cerebral hemodynamics and increases the incidence and severity of brain injury in ventilated preterm lambs. PMID- 22052872 TI - Similar changes of gene expression in human skeletal muscle after resistance exercise and multiple fine needle biopsies. AB - Repeated biopsy sampling from one muscle is necessary to investigate muscular adaptation to different forms of exercise as adaptation is thought to be the result of cumulative effects of transient changes in gene expression in response to single exercise bouts. In a crossover study, we obtained four fine needle biopsies from one vastus lateralis muscle of 11 male subjects (25.9 +/- 3.8 yr, 179.2 +/- 4.8 cm, 76.5 +/- 7.0 kg), taken before (baseline), 1, 4, and 24 h after one bout of squatting exercise performed as conventional squatting or as whole body vibration exercise. To investigate if the repeated biopsy sampling has a confounding effect on the observed changes in gene expression, four fine needle biopsies from one vastus lateralis muscle were also taken from 8 male nonexercising control subjects (24.5 +/- 3.7 yr, 180.6 +/- 1.2 cm, 81.2 +/- 1.6 kg) at the equivalent time points. Using RT-PCR, we observed similar patterns of change in the squatting as well as in the control group for the mRNAs of interleukin 6 (IL-6), IL-6 receptor, insulin-like growth factor 1, p21, phosphofructokinase, and glucose transporter in relation to the baseline biopsy. In conclusion, multiple fine needle biopsies obtained from the same muscle region can per se influence the expression of marker genes induced by an acute bout of resistance exercise. PMID- 22052873 TI - Resistance exercise training influences skeletal muscle immune activation: a microarray analysis. AB - The primary aim of this investigation was to evaluate the effect of training on the immune activation in skeletal muscle in response to an acute bout of resistance exercise (RE). Seven young healthy men and women underwent a 12-wk supervised progressive unilateral arm RE training program. One week after the last training session, subjects performed an acute bout of bilateral RE in which the trained and the untrained arm exercised at the same relative intensity. Muscle biopsies were obtained 4 h postexercise from the biceps brachii of both arms and assessed for global transcriptom using Affymetrix U133 plus 2.0 microarrays. Significantly regulated biological processes and gene groups were analyzed using a logistic regression-based method following differential (trained vs. untrained) gene expression testing via an intensity-based Bayesian moderated t-test. The results from the present study suggest that training blunts the transcriptional upregulation of immune activation by minimizing expression of genes involved in monocyte recruitment and enhancing gene expression involved in macrophage anti-inflammatory polarization. Additionally, our data suggest that training blunts the transcriptional upregulation of the stress response and the downregulation of glucose metabolism, mitochondrial structure, and oxidative phosphorylation, and it enhances the transcriptional upregulation of the extracellular matrix and cytoskeleton development and organization and the downregulation of gene transcription and muscle contraction. This study provides novel insight into the molecular processes involved in the adaptive response of skeletal muscle following RE training and the cellular and molecular events implicating the protective role of training on muscle stress and damage inflicted by acute mechanical loading. PMID- 22052874 TI - Impact of repeated daily exposure to intermittent hypoxia and mild sustained hypercapnia on apnea severity. AB - We examined whether exposure to intermittent hypoxia (IH) during wakefulness impacted on the apnea/hypopnea index (AHI) during sleep in individuals with sleep apnea. Participants were exposed to twelve 4-min episodes of hypoxia in the presence of sustained mild hypercapnia each day for 10 days. A control group was exposed to sustained mild hypercapnia for a similar duration. The intermittent hypoxia protocol was completed in the evening on day 1 and 10 and was followed by a sleep study. During all sleep studies, the change in esophageal pressure (DeltaPes) from the beginning to the end of an apnea and the tidal volume immediately following apneic events were used to measure respiratory drive. Following exposure to IH on day 1 and 10, the AHI increased above baseline measures (day 1: 1.95 +/- 0.42 fraction of baseline, P <= 0.01, vs. day 10: 1.53 +/- 0.24 fraction of baseline, P < 0.06). The indexes were correlated to the hypoxic ventilatory response (HVR) measured during the IH protocol but were not correlated to the magnitude of ventilatory long-term facilitation (vLTF). Likewise, DeltaPes and tidal volume measures were greater on day 1 and 10 compared with baseline (DeltaPes: -8.37 +/- 0.84 vs. -5.90 +/- 1.30 cmH(2)0, P <= 0.04; tidal volume: 1,193.36 +/- 101.85 vs. 1,015.14 +/- 119.83 ml, P <= 0.01). This was not the case in the control group. Interestingly, the AHI on day 10 (0.78 +/- 0.13 fraction of baseline, P <= 0.01) was significantly less than measures obtained during baseline and day 1 in the mild hypercapnia control group. We conclude that enhancement of the HVR initiated by exposure to IH may lead to increases in the AHI during sleep and that initiation of vLTF did not appear to impact on breathing stability. Lastly, our results suggest that repeated daily exposure to mild sustained hypercapnia may lead to a decrease in breathing events. PMID- 22052875 TI - A systematic method to quantify the presence of cross-talk in stimulus-evoked EMG responses: implications for TMS studies. AB - Surface electromyography (EMG) responses to noninvasive nerve and brain stimulation are routinely used to provide insight into neural function in humans. However, this could lead to erroneous conclusions if evoked EMG responses contain significant contributions from neighboring muscles (i.e., due to "cross-talk"). We addressed this issue with a simple nerve stimulation method to provide quantitative information regarding the size of EMG cross-talk between muscles of the forearm and hand. Peak to peak amplitude of EMG responses to electrical stimulation of the radial, median, and ulnar nerves (i.e., M-waves) were plotted against stimulation intensity for four wrist muscles and two hand muscles (n = 12). Since electrical stimulation can selectively activate specific groups of muscles, the method can differentiate between evoked EMG arising from target muscles and EMG cross-talk arising from nontarget muscles. Intramuscular EMG responses to nerve stimulation and root mean square EMG produced during maximal voluntary contractions (MVC) of the wrist were recorded for comparison. Cross talk was present in evoked surface EMG responses recorded from all nontarget wrist (5.05-39.38% Mmax) and hand muscles (1.50-24.25% Mmax) and to a lesser degree in intramuscular EMG signals (~3.7% Mmax). The degree of cross-talk was comparable for stimulus-evoked responses and voluntary activity recorded during MVC. Since cross-talk can make a considerable contribution to EMG responses in forearm and hand muscles, care is required to avoid misinterpretation of EMG data. The multiple nerve stimulation method described here can be used to quantify the potential contribution of EMG cross-talk in transcranial magnetic stimulation and reflex studies. PMID- 22052876 TI - Maternal diesel inhalation increases airway hyperreactivity in ozone-exposed offspring. AB - Air pollutant exposure is linked with childhood asthma incidence and exacerbations, and maternal exposure to airborne pollutants during pregnancy increases airway hyperreactivity (AHR) in offspring. To determine if exposure to diesel exhaust (DE) during pregnancy worsened postnatal ozone-induced AHR, timed pregnant C57BL/6 mice were exposed to DE (0.5 or 2.0 mg/m(3)) 4 hours daily from Gestation Day 9-17, or received twice-weekly oropharyngeal aspirations of the collected DE particles (DEPs). Placentas and fetal lungs were harvested on Gestation Day 18 for cytokine analysis. In other litters, pups born to dams exposed to air or DE, or to dams treated with aspirated diesel particles, were exposed to filtered air or 1 ppm ozone beginning the day after birth, for 3 hours per day, 3 days per week for 4 weeks. Additional pups were monitored after a 4 week recovery period. Diesel inhalation or aspiration during pregnancy increased levels of placental and fetal lung cytokines. There were no significant effects on airway leukocytes, but prenatal diesel augmented ozone-induced elevations of bronchoalveolar lavage cytokines at 4 weeks. Mice born to the high-concentration diesel-exposed dams had worse ozone-induced AHR, which persisted in the 4-week recovery animals. Prenatal diesel exposure combined with postnatal ozone exposure also worsened secondary alveolar crest development. We conclude that maternal inhalation of DE in pregnancy provokes a fetal inflammatory response that, combined with postnatal ozone exposure, impairs alveolar development, and causes a more severe and long-lasting AHR to ozone exposure. PMID- 22052877 TI - Phosphatidylglycerol suppresses influenza A virus infection. AB - Influenza A virus (IAV) is a worldwide public health problem causing 500,000 deaths each year. Palmitoyl-oleoyl-phosphatidylglycerol (POPG) is a minor component of pulmonary surfactant, which has recently been reported to exert potent regulatory functions upon the innate immune system. In this article, we demonstrate that POPG acts as a strong antiviral agent against IAV. POPG markedly attenuated IL-8 production and cell death induced by IAV in cultured human bronchial epithelial cells. The lipid also suppressed viral attachment to the plasma membrane and subsequent replication in Madin-Darby canine kidney cells. Two virus strains, H1N1-PR8-IAV and H3N2-IAV, bind to POPG with high affinity, but exhibit only low-affinity interactions with the structurally related lipid, palmitoyl-oleoyl-phosphatidylcholine. Intranasal inoculation of H1N1-PR8-IAV in mice, in the presence of POPG, markedly suppressed the development of inflammatory cell infiltrates, the induction of IFN-gamma recovered in bronchoalveolar lavage, and viral titers recovered from the lungs after 5 days of infection. These findings identify supplementary POPG as a potentially important new approach for treatment of IAV infections. PMID- 22052878 TI - Cardiac physiologic and genetic predictors of hyperoxia-induced acute lung injury in mice. AB - Exposure of mice to hyperoxia produces pulmonary toxicity similar to acute lung injury/acute respiratory distress syndrome, but little is known about the interactions within the cardiopulmonary system. This study was designed to characterize the cardiopulmonary response to hyperoxia, and to identify candidate susceptibility genes in mice. Electrocardiogram and ventilatory data were recorded continuously from 4 inbred and 29 recombinant inbred strains during 96 hours of hyperoxia (100% oxygen). Genome-wide linkage analysis was performed in 27 recombinant inbred strains against response time indices (TIs) calculated from each cardiac phenotype. Reductions in minute ventilation, heart rate (HR), low frequency (LF) HR variability (HRV), high-frequency HRV, and total power HRV were found in all mice during hyperoxia exposure, but the lag time before these changes began was strain dependent. Significant (chromosome 9) or suggestive (chromosomes 3 and 5) quantitative trait loci were identified for the HRTI and LFTI. Functional polymorphisms in several candidate susceptibility genes were identified within the quantitative trait loci and were associated with hyperoxia susceptibility. This is the first study to report highly significant interstrain variation in hyperoxia-induced changes in minute ventilation, HR, and HRV, and to identify polymorphisms in candidate susceptibility genes that associate with cardiac responses. Results indicate that changes in HR and LF HRV could be important predictors of subsequent adverse outcome during hyperoxia exposure, specifically the pathogenesis of acute lung injury. Understanding the genetic mechanisms of these responses may have significant diagnostic clinical value. PMID- 22052879 TI - Deletion of apoptosis signal-regulating kinase-1 prevents ventilator-induced lung injury in mice. AB - Both hyperoxia and mechanical ventilation can independently cause lung injury. In combination, these insults produce accelerated and severe lung injury. We recently reported that pre-exposure to hyperoxia for 12 hours, followed by ventilation with large tidal volumes, induced significant lung injury and epithelial cell apoptosis compared with either stimulus alone. We also reported that such injury and apoptosis are inhibited by antioxidant treatment. In this study, we hypothesized that apoptosis signal-regulating kinase-1 (ASK-1), a redox sensitive, mitogen-activated protein kinase kinase kinase, plays a role in lung injury and apoptosis in this model. To determine the role of ASK-1 in lung injury, the release of inflammatory mediators and apoptosis, attributable to 12 hours of hyperoxia, were followed by large tidal volume mechanical ventilation with hyperoxia. Wild-type and ASK-1 knockout mice were subjected to hyperoxia (Fi(O(2)) = 0.9) for 12 hours before 4 hours of large tidal mechanical ventilation (tidal volume = 25 MUl/g) with hyperoxia, and were compared with nonventilated control mice. Lung injury, apoptosis, and cytokine release were measured. The deletion of ASK-1 significantly inhibited lung injury and apoptosis, but did not affect the release of inflammatory mediators, compared with the wild-type mice. ASK-1 is an important regulator of lung injury and apoptosis in this model. Further study is needed to determine the mechanism of lung injury and apoptosis by ASK-1 and its downstream mediators in the lung. PMID- 22052880 TI - Which of satellite- or model-based estimates is closer to reality for aerosol indirect forcing? PMID- 22052881 TI - T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses. AB - Reactions to pathogens are usually tuned to effect immunity and limit tissue damage. Several host counterinflammatory mechanisms inhibit tissue damage but these may also act to constrain the effectiveness of immunity to acute infections, as we demonstrate in mice acutely infected with influenza A virus (IAV). We show that compared with wild type (WT), galectin-9 knockout (G9KO) mice mounted a more robust acute phase virus-specific CD8 T-cell response as well as higher and more rapid virus-specific serum IgM, IgG, and IgA responses and also cleared virus more rapidly than did WT mice. Blocking galectin-9 signals to Tim-3 expressing cells using a Tim-3 fusion protein resulted in improved immune responses in WT mice. When IAV immune mice were challenged with a heterologous IAV, the secondary IAV-specific CD8 T-cell responses were four- to fivefold higher in G9KO compared with WT mice. Our results indicate that manipulating galectin signals may represent a convenient approach to improve immune responses to some vaccines. PMID- 22052882 TI - Primary IgA nephropathy in north India: is it different? AB - BACKGROUND: Immunoglobulin A (IgA) nephropathy is the most common glomerulonephritis worldwide, but has a variable geographic distribution. the bulk of the disease burden is borne by asian countries. however, its exact prevalence or clinicopathologic spectrum in india is not well documented. METHODS: This cross sectional study analysed the renal biopsy findings and clinical features at presentation in 66 patients of primary IgA nephropathy diagnosed over a period of 2 years (2007-2008). The results were compared with studies from other centres in the country and elsewhere. RESULTS: IgA nephropathy comprised 8.1% of all native kidney biopsies. The mean age of the patients was 29.9 years with a male:female ratio of 4.4:1. Most patients presented with renal failure and a significant percentage (23%) also had nephrotic range proteinuria. Renal biopsies were classified by the Haas classification and were further scored by the MEST scoring system of the Oxford classification. By Haas classification, 41 cases (62%) showed advanced sclerotic lesions of class V. Active crescents (cellular or fibrocellular) were seen in 42% of cases, and 26% of cases showed endocapillary proliferation. Serum creatinine values were highest in the presence of proliferative lesions. MEST scoring of the Oxford classification was not applicable in approximately 18% of cases because of the presence of advanced sclerotic lesions. On immunofluorescence, the majority of the cases showed both mesangial and membranous positivity for IgA antisera. Electron microscopy revealed para-mesangial location of immune complex deposition in the majority of the cases. It also showed glomerular basement membrane abnormalities in two cases. CONCLUSION: Comparison of clinical and pathological features revealed that this disease presents as an advanced disease in much younger individuals in this study compared to other studies. Elucidation of the underlying factors may have immense therapeutic implications. PMID- 22052883 TI - Effect of rating scales on scores given to junior doctors in multi-source feedback. AB - BACKGROUND: Multi-source feedback (MSF) has an established role in the workplace based assessment of doctors in training. Different models of MSF are currently used in different training programmes and settings. One important way in which these models differ is the rating scale on which assessors score the trainee. The aim of this study was to explore the effect of rating scale on MSF scores. METHODS: Foundation Year 2 trainees in hospitals in the West Midlands underwent MSF using the validated MSF tool, team assessment of behaviour (TAB) in autumn 2005. Trainees were scored with TAB using one of four different rating scales, ranging from 3- to 9-point scales. Each participating hospital used only one rating scale. The proportions of trainees scored as having potential problems were related to the different rating scale used. Similarly, the proportions scored as 'above expectations' were compared. Assessors also completed a short questionnaire regarding the assessment. RESULTS: 245 trainees underwent 2594 assessments. Longer rating scales were associated with a lower proportion of trainees awarded 'problem' scores and higher proportions of trainees scored as 'above expectations'. Assessors generally reported no difficulties whichever rating scale they had used. CONCLUSION: Careful consideration, recognising its potential impact on assessment score, should be given to the rating scale used when instituting MSF within a system of workplace based assessment. PMID- 22052884 TI - Controversies and advances in non-steroidal anti-inflammatory drug (NSAID) analgesia in chronic pain management. AB - Chronic pain can lead to significant disability with social and economic implications in the community. Traditional non-steroidal anti-inflammatory drugs (NSAIDs) have been part of the management of chronic pain. The risk of adverse events with traditional NSAIDs has led to the development of alternative therapeutic options. Differential blockade of the enzymes involved in pain and inflammation can offer therapeutic options without the gastrointestinal side effects. However, this may be at the expense of other major cardiovascular side effects. Pain pathways that involve peripheral transmission may be altered by local application of analgesia to the skin overlying the painful area. Recent guidelines for osteoarthritis treatment from the National Institute for Health and Clinical Excellence highlight the importance of topical NSAIDs in the armamentarium of pain management. NSAID combination drugs with gastric protection have provided alternatives to traditional NSAIDs, but the long-term sequelae are unknown. PMID- 22052885 TI - Comparison of the early fungicidal activity of high-dose fluconazole, voriconazole, and flucytosine as second-line drugs given in combination with amphotericin B for the treatment of HIV-associated cryptococcal meningitis. AB - BACKGROUND: HIV-associated cryptococcal meningitis is associated with an estimated 600 000 deaths worldwide per year. Current standard initial therapy consists of amphotericin B (AmB) plus flucytosine (5-FC), but 5-FC remains largely unavailable in Asia and Africa. Alternative, more widely available, and/or more effective antifungal combination treatment regimens are urgently needed. METHODS: Eighty HIV-seropositive, antiretroviral naive patients presenting with cryptococcal meningitis were randomized to 4 treatment arms of 2 weeks duration: group 1, AmB (0.7-1 mg/kg) and 5-FC (25 mg/kg 4 times daily); group 2, AmB (0.7-1 mg/kg) and fluconazole (800 mg daily); group 3, AmB (0.7-1 mg/kg) and fluconazole (600 mg twice daily); and group 4, AmB (0.7-1 mg/kg) and voriconazole (300 mg twice daily). The primary end point was the rate of clearance of infection from the cerebrospinal fluid (CSF) or early fungicidal activity (EFA), as determined by results of serial, quantitative CSF cryptococcal cultures. RESULTS: There were no statistically significant differences in the rate of clearance of cryptococcal colony-forming units (CFU) in CSF samples among the 4 treatment groups; the mean (+/-standard deviation) EFA for treatment groups 1, 2, 3, and 4 were -0.41 +/- 0.22 log CFU/mL CSF/day, -0.38 +/- 0.18 log CFU/mL CSF/day, -0.41 +/- 0.35 log CFU/mL CSF/day, and -0.44 +/- 0.20 log CFU/mL CSF/day, respectively. Overall mortality was 12% (9 of 78 patients died) at 2 weeks and 29% (22 of 75 patients died) at 10 weeks, with no statistically significant differences among groups. There were few laboratory abnormalities related to the second agents given; in particular, there were no statistically significant (>=grade 3) increases in alanine transaminase level or decreases in neutrophil count. CONCLUSIONS: There was no statistically significant difference in EFA between AmB in combination with fluconazole and AmB plus 5-FC for the treatment of HIV-associated cryptococcal meningitis. AmB plus fluconazole (800 1200 mg/day) represents an immediately implementable alternative to AmB plus 5 FC. AmB plus voriconazole is an effective alternative combination in patients not receiving interacting medications. PMID- 22052886 TI - Companion drugs for amphotericin B in cryptococcal meningitis: flucytosine, fluconazole, or...Nothing? PMID- 22052887 TI - Boosting heterosubtypic neutralization antibodies in recipients of 2009 pandemic H1N1 influenza vaccine. AB - BACKGROUND: A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. METHODS: We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. RESULTS: One dose of pandemic vaccine not only stimulated good neutralization antibodies against cognate influenza virus 2009 influenza A (H1N1), but also raised broad cross-reactive neutralization activities against seasonal H3N2 and highly pathogenic avian influenza virus H5N1 and lesser to H2N2. The cross-reactive neutralization activities were completely abolished after the removal of immunoglobin G (IgG). In contrast, H1N1 vaccination alone in influenza-naive mice elicited only vigorous homologous neutralizing activities but not cross-reactive neutralization activities. CONCLUSIONS: Our data suggest that the cross-reactive neutralization epitopes do exist in this vaccine and could elicit significant cross-reactive neutralizing IgG antibodies in the presence of preexisting responses. The exposure to H1N1 vaccine is likely to modify the hierarchical order of preexisting immune responses to influenza viruses. These findings provide insights into the evolution of human immunity to influenza viruses after experiencing multiple influenza virus infections and vaccinations. PMID- 22052888 TI - Prevalence of and risk factors for hepatitis B viremia after spontaneous hepatitis B surface antigen seroclearance in hepatitis B carriers. AB - In 118 previous hepatitis B surface antigen (HBsAg) carriers, low-level hepatitis B (HBV) viremia persisted at a rate of 15%-20% for >10 years after HBsAg seroclearance. The frequency of HBV viremia was significantly (P = .002) lower in patients with anti-HBsAg seroconversion (6 of 69 [8.7%]) than in those without seroconversion (15 of 49 [30.6%]). PMID- 22052889 TI - Consumption of street-vended beverage a potential exposure risk for non-O157 enterohemorrhagic Escherichia coli infection: the importance of testing for virulence loci. PMID- 22052890 TI - Fatal outcomes in family transmission of Mycoplasma pneumoniae. AB - BACKGROUND: Mycoplasma pneumoniae continues to be a significant cause of community-acquired pneumonia and, on rare occasions, manifests as fulminant disease that leads to mortality, even in healthy individuals. METHODS: We conducted a retrospective study on members of a family who were quarantined by the Centers for Disease Control and Prevention in 2002 for respiratory failure and death of a 15-year-old brother (sibling 1) and a 13-year-old sister (sibling 2). Collected airway, cerebrospinal fluid (CSF), and serum samples from both deceased siblings and serum samples from both parents and the remaining 3 ill siblings (sibling 3-5) were tested using a range of diagnostic assays. Autopsy lung tissue samples from sibling 2 were also assessed using immunohistochemical and immunoelectron microscopic methods. RESULTS: Autopsy evaluation of sibling 1 revealed cerebral edema consistent with hypoxic ischemic encepatholopathy and pulmonary findings of bronchiolitis obliterans with organizing pneumonia (BOOP). Postmortem lung examination of sibling 2 revealed lymphoplasmacytic bronchiolitis with intraluminal purulent exudate, BOOP, and pulmonary edema. Results of diagnostic assays implicated the household transmission of M. pneumoniae among all 5 siblings and both parents. Further analysis of lung tissue from sibling 2 demonstrated the presence of M. pneumoniae organisms and community-acquired respiratory distress syndrome toxin. M. pneumoniae was cultured directly from sibling 2 autopsy lung tissue. CONCLUSION: Evidence is provided that M. pneumoniae was readily transmitted to all members of the household and that the resulting infections led to a spectrum of individual responses with variation in disease progression, including lymphoplasmacytic bronchiolitis, BOOP, and death. PMID- 22052891 TI - Tuberculosis incidence at the Burundi-Rwanda border 15 years after the civil war. PMID- 22052892 TI - Decreased prevalence of anemia in highland areas of low malaria transmission after a 1-year interruption of transmission. AB - BACKGROUND: Malaria control campaigns have reduced malaria transmission to very low levels in many areas of Africa. Yet the extent to which malaria interruption or elimination might decrease the prevalence of anemia in areas of low malaria transmission is unknown. METHODS: Kapsisiywa and Kipsamoite, highland areas of Kenya with low, unstable malaria transmission, experienced a 12-month interruption in malaria transmission from April 2007 to May 2008, following high level coverage (>70% of households) with indoor residual insecticide spraying in 2007. Hemoglobin levels were tested in 1697 randomly selected asymptomatic residents of Kapsisiywa (n = 910) and Kipsamoite (n = 787) at the beginning of a 12-month period of interrupted transmission (in May 2007) and 14 months later (in July 2008). RESULTS: From May 2007 to July 2008, only 1 of 1697 study cohort members developed clinical malaria. In this period, the prevalence of anemia decreased in Kapsisiywa in all age groups (from 57.5% to 37.9% in children aged <5 years [P < .001], from 21.7% to 10.5% in children aged 5-14 years [P < .001], and from 22.7% to 16.6% in individuals aged >= 15 years [P = .004]). The prevalence of anemia in Kipsamoite also decreased in children aged <5 years (from 47.2% to 31.3%; P = .001) but was unchanged in children aged 5-14 years and in individuals aged >=15 years. Among children <5 years, anemia prevalence was reduced by 34% in both Kapsisiywa (95% confidence interval [CI], 21%-45%) and Kipsamoite (95% CI, 16%-48%). CONCLUSIONS: Successful malaria elimination or interruption may lead to substantial reductions in anemia prevalence even in areas of very low transmission. PMID- 22052893 TI - Prolonged protection provided by a single dose of atovaquone-proguanil for the chemoprophylaxis of Plasmodium falciparum malaria in a human challenge model. AB - BACKGROUND: We conducted a randomized, placebo-controlled, double-blind trial to establish the efficacy of atovaquone-proguanil to prevent malaria with the goal of simulating weekly dosing in a human Plasmodium falciparum challenge model. METHODS: Thirty volunteers randomly received 1 of the following dose regimens: (1) 250 milligrams of atovaquone and 100 milligrams of proguanil (250/100 milligrams) 1 day prior to infectious mosquito challenge (day -1), (2) 250/100 milligrams on day 4 after challenge, (3) 250/100 milligrams on day -7, (4) 500 milligrams of atovaquone and 200 milligrams of proguanil (500/200 milligrams) on day -7 or, (5) 1000 milligrams of atovaquone and 400 milligrams of proguanil (1000/400 milligrams) on day -7. All regimens included matching placebo such that all volunteers received identical pill numbers. Six volunteers served as open label infectivity controls. Volunteers underwent mosquito sporozoite challenge with P. falciparum 3D7 strain. Follow-up consisted of serial microscopy and close clinical monitoring for 90 days. RESULTS: Six of 6 infectivity controls developed parasitemia as expected. Two of 5 evaluable volunteers receiving 250/100 milligrams 7 days prior to challenge and 1 of 6 volunteers receiving 1000/400 milligrams 7 days prior to challenge were microscopically diagnosed with malaria. All other volunteers were protected. Atovaquone exposure (area under the curve) during liver stage development was low in 2 of 3 volunteers with prophylactic failure (423 and 199 ng/mL * days compared with a mean for protected volunteers of 1903 ng/mL * days), as was peak concentration (165 and 81 ng/mL compared with a mean of 594 ng/mL in volunteers with prophylactic success). Elimination half life was short in volunteers with prophylactic failure (2.4, 2.0, and 3.3 days compared with a mean of 4.1 days in volunteers with prophylactic success). CONCLUSIONS: Single-dose atovaquone-proguanil provides effective malaria chemoprophylaxis against P. falciparum challenge at dosing intervals supportive of weekly dosing. Postexposure prophylaxis 4 days after challenge was 100% effective. PMID- 22052894 TI - Risk factors for Staphylococcus aureus postpartum breast abscess. AB - BACKGROUND: Staphylococcus aureus (SA) breast abscesses are a complication of the postpartum period. Risk factors for postpartum SA breast abscesses are poorly defined, and literature is conflicting. Whether risk factors for methicillin resistant SA (MRSA) and methicillin-susceptible SA (MSSA) infections differ is unknown. We describe novel risk factors associated with postpartum breast abscesses and the changing epidemiology of this infection. METHODS: We conducted a cohort study with a nested case-control study (n = 216) involving all patients with culture-confirmed SA breast abscess among >30 000 deliveries at our academic tertiary care center from 2003 through 2010. Data were collected from hospital databases and through abstraction from medical records. All SA cases were compared with both nested controls and full cohort controls. A subanalysis was completed to determine whether risk factors for MSSA and MRSA breast abscess differ. Univariate analysis was completed using Student's t test, Wilcoxon rank sum test, and analysis of variance, as appropriate. A multivariable stepwise logistic regression was used to determine final adjusted results for both the case-control and the cohort analyses. RESULTS: Fifty-four cases of culture confirmed abscess were identified: 30 MRSA and 24 MSSA. Risk factors for postpartum SA breast abscess in multivariable analysis include in-hospital identification of a mother having difficulty breastfeeding (odds ratio, 5.00) and being a mother employed outside the home (odds ratio, 2.74). Risk factors did not differ between patients who developed MRSA and MSSA infections. CONCLUSIONS: MRSA is an increasingly important pathogen in postpartum women; risk factors for postpartum SA breast abscess have not changed with the advent of community associated MRSA. PMID- 22052895 TI - In memoriam: James J. Rahal Jr, MD. PMID- 22052896 TI - Culture-confirmed multidrug-resistant tuberculosis in children: clinical features, treatment, and outcome. AB - BACKGROUND: Multidrug-resistant (MDR) tuberculosis in children is frequently associated with delayed diagnosis and treatment. There is limited evidence regarding the management and outcome of children with MDR-tuberculosis. METHODS: All children <15 years of age with a diagnosis of culture-confirmed MDR tuberculosis were included in this retrospective cohort study from 1 January 2003 to 31 December 2008, with follow-up documented until 31 May 2011. We identified children from Brooklyn Hospital for Chest Diseases and Tygerberg Children's Hospital, Western Cape Province, South Africa. Treatment outcomes were defined as 2-month sputum-culture conversion, treatment episode outcome, and survival. RESULTS: A total of 111 children (median age, 50 months) were included. The diagnosis was delayed in children who had no identified MDR-tuberculosis index case (median delay, 123 vs 58 days; P < .001). Sixty-two percent of patients (53 of 85) were sputum-smear positive, and 43% of patients (43 of 100) were human immunodeficiency virus (HIV) infected. Overall, 82% had favorable treatment outcomes; total mortality was 12%. Malnutrition was associated with failure to culture-convert at 2 months (odds ratio [OR], 4.49 [95% confidence interval {CI}, 1.32-15.2]; P = .02) and death (OR, 15.0 [95% CI, 1.17-192.5]; P = .04) in multivariate analysis. HIV coinfection (OR, 24.7 [95% CI, 1.79-341.1]; P = .02) and the presence of extrapulmonary tuberculosis (OR, 37.8 [95% CI, 2.78-513.4]; P = .006) predicted death. CONCLUSIONS: Despite advanced disease at presentation and a high prevalence of human immunodeficiency virus coinfection, children with MDR-tuberculosis can be treated successfully, using individualized treatment under routine conditions. PMID- 22052897 TI - Impact of electronic health record implementation on patient flow metrics in a pediatric emergency department. AB - Implementing electronic health records (EHR) in healthcare settings incurs challenges, none more important than maintaining efficiency and safety during rollout. This report quantifies the impact of offloading low-acuity visits to an alternative care site from the emergency department (ED) during EHR implementation. In addition, the report evaluated the effect of EHR implementation on overall patient length of stay (LOS), time to medical provider, and provider productivity during implementation of the EHR. Overall LOS and time to doctor increased during EHR implementation. On average, admitted patients' LOS was 6-20% longer. For discharged patients, LOS was 12-22% longer. Attempts to reduce patient volumes by diverting patients to another clinic were not effective in minimizing delays in care during this EHR implementation. Delays in ED throughput during EHR implementation are real and significant despite additional providers in the ED, and in this setting resolved by 3 months post implementation. PMID- 22052898 TI - A multi-layered framework for disseminating knowledge for computer-based decision support. AB - BACKGROUND: There are several challenges in encoding guideline knowledge in a form that is portable to different clinical sites, including the heterogeneity of clinical decision support (CDS) tools, of patient data representations, and of workflows. METHODS: We have developed a multi-layered knowledge representation framework for structuring guideline recommendations for implementation in a variety of CDS contexts. In this framework, guideline recommendations are increasingly structured through four layers, successively transforming a narrative text recommendation into input for a CDS system. We have used this framework to implement rules for a CDS service based on three guidelines. We also conducted a preliminary evaluation, where we asked CDS experts at four institutions to rate the implementability of six recommendations from the three guidelines. CONCLUSION: The experience in using the framework and the preliminary evaluation indicate that this approach has promise in creating structured knowledge, to implement in CDS systems, that is usable across organizations. PMID- 22052899 TI - Guided medication dosing for elderly emergency patients using real-time, computerized decision support. AB - OBJECTIVE: To evaluate the impact of a real-time computerized decision support tool in the emergency department that guides medication dosing for the elderly on physician ordering behavior and on adverse drug events (ADEs). DESIGN: A prospective controlled trial was conducted over 26 weeks. The status of the decision support tool alternated OFF (7/17/06-8/29/06), ON (8/29/06-10/10/06), OFF (10/10/06-11/28/06), and ON (11/28/06-1/16/07) in consecutive blocks during the study period. In patients >=65 who were ordered certain benzodiazepines, opiates, non-steroidals, or sedative-hypnotics, the computer application either adjusted the dosing or suggested a different medication. Physicians could accept or reject recommendations. MEASUREMENTS: The primary outcome compared medication ordering consistent with recommendations during ON versus OFF periods. Secondary outcomes included the admission rate, emergency department length of stay for discharged patients, 10-fold dosing orders, use of a second drug to reverse the original medication, and rate of ADEs using previously validated explicit chart review. RESULTS: 2398 orders were placed for 1407 patients over 1548 visits. The majority (49/53; 92.5%) of recommendations for alternate medications were declined. More orders were consistent with dosing recommendations during ON (403/1283; 31.4%) than OFF (256/1115; 23%) periods (p<=0.0001). 673 (43%) visits were reviewed for ADEs. The rate of ADEs was lower during ON (8/237; 3.4%) compared with OFF (31/436; 7.1%) periods (p=0.02). The remaining secondary outcomes showed no difference. LIMITATIONS: Single institution study, retrospective chart review for ADEs. CONCLUSION: Though overall agreement with recommendations was low, real-time computerized decision support resulted in greater acceptance of medication recommendations. Fewer ADEs were observed when computerized decision support was active. PMID- 22052900 TI - Cost-effectiveness of a shared computerized decision support system for diabetes linked to electronic medical records. AB - BACKGROUND: Computerized decision support systems (CDSSs) are believed to enhance patient care and reduce healthcare costs; however the current evidence is limited and the cost-effectiveness remains unknown. OBJECTIVE: To estimate the long-term cost-effectiveness of a CDSS linked to evidence-based treatment recommendations for type 2 diabetes. METHODS: Using the Ontario Diabetes Economic Model, changes in factors (eg, HbA1c) from a randomized controlled trial were used to estimate cost-effectiveness. The cost of implementation, development, and maintenance of the core dataset, and projected diabetes-related complications were included. The base case assumed a 1-year treatment effect, 5% discount rate, and 40-year time horizon. Univariate, one-way sensitivity analyses were carried out by altering different parameter values. The perspective was the Ontario Ministry of Health and costs were in 2010 Canadian dollars. RESULTS: The cost of implementing the intervention was $483,699. The one-year intervention reduced HbA1c by 0.2 and systolic blood pressure by 3.95 mm Hg, but increased body mass index by 0.02 kg/m2, resulting in a relative risk reduction of 14% in the occurrence of amputation. The model estimated that the intervention resulted in an additional 0.0117 quality-adjusted life year; the incremental cost-effectiveness ratio was $160,845 per quality-adjusted life-year. CONCLUSION: The web-based prototype decision support system slightly improved short-term risk factors. The model predicted moderate improvements in long-term health outcomes. This disease management program will need to develop considerable efficiencies in terms of costs and processes or improved effectiveness to be considered a cost-effective intervention for treating patients with type 2 diabetes. PMID- 22052901 TI - Cost-effectiveness analysis of continuous-flow left ventricular assist devices as destination therapy. AB - BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) have become the dominant devices for mechanical circulatory support, but their cost effectiveness is undetermined. This study assessed the cost-effectiveness of continuous-flow devices for destination therapy versus optimal medical management in advanced heart failure and compared the results with previous estimates for pulsatile devices. METHODS AND RESULTS: A Markov model was developed to assess cost-effectiveness. Survival, hospitalization rates, quality of life, and cost data were obtained for advanced heart failure patients treated medically or with a continuous-flow LVAD. Rates of clinical outcomes for all patients were obtained from clinical trial databases. Medicare prospective payments were used to estimate the cost of heart failure admissions. The cost of LVAD implantation was obtained prospectively from hospital claims within a clinical trial. Compared with medically managed patients, continuous-flow LVAD patients had higher 5-year costs ($360 407 versus $62 856), quality-adjusted life years (1.87 versus 0.37), and life years (2.42 versus 0.64). The incremental cost-effectiveness ratio of the continuous-flow device was $198 184 per quality-adjusted life year and $167 208 per life year. This equates to a 75% reduction in incremental cost effectiveness ratio compared with the $802 700 per quality-adjusted life year for the pulsatile-flow device. The results were most sensitive to the cost of device implantation, long-term survival, cost per rehospitalization, and utility associated with patients' functional status. CONCLUSIONS: The cost-effectiveness associated with continuous-flow LVADs for destination therapy has improved significantly relative to the pulsatile flow devices. This change is explained by significant improvements in survival and functional status and reduction in implantation costs. PMID- 22052902 TI - Interactions with the substrate phenolic group are essential for hydroxylation by the oxygenase component of p-hydroxyphenylacetate 3-hydroxylase. AB - p-Hydroxyphenylacetate (HPA) 3-hydroxylase is a two-component flavoprotein monooxygenase that catalyzes the hydroxylation of p-hydroxyphenylacetate to form 3,4-dihydroxyphenylacetate. Based on structures of the oxygenase component (C(2)), both His-120 and Ser-146 are located ~2.8 A from the hydroxyl group of HPA. The variants H120N, H120Q, H120Y, H120D, and H120E can form C4a-hydroperoxy FMN (a reactive intermediate necessary for hydroxylation) but cannot hydroxylate HPA. The impairment of H120N is not due to substrate binding because the variant can still bind HPA. In contrast, the H120K variant catalyzes hydroxylation with efficiency comparable with that of the wild-type enzyme; the hydroxylation rate constant for H120K is 5.7 +/- 0.6 s(-1), and the product conversion ratio is 75%, compared with values of 16 s(-1) and 90% for the wild-type enzyme. H120R can also catalyze hydroxylation, suggesting that a positive charge on residue 120 can substitute for the hydroxylation function of His-120. Because the hydroxylation reaction of wild-type C(2) is pH-independent between pH 6 and 10, the protonation status of key components required for hydroxylation likely remains unchanged in this pH range. His-120 may be positively charged for selective binding to the phenolate form of HPA, i.e. to form the His(delta+).HPA(delta-) complex, which in turn promotes oxygen atom transfer via an electrophilic aromatic substitution mechanism. Analysis of Ser-146 variants revealed that this residue is necessary for but not directly engaged in hydroxylation. Product formation in S146A is pH independent and constant at ~70% over a pH range of 6-10, whereas product formation for S146C decreased from ~65% at pH 6.0 to 27% at pH 10.0. These data indicate that the ionization of Cys-146 in the S146C variant has an adverse effect on hydroxylation, possibly by perturbing formation of the His(delta+).HPA(delta-) complex needed for hydroxylation. PMID- 22052903 TI - Proapoptotic protein Smac mediates apoptosis in cisplatin-resistant ovarian cancer cells when treated with the anti-tumor agent AT101. AB - Chemoresistance of ovarian cancer has been previously attributed to the expression and activation of Bcl-2 family proteins. BH3-mimetic molecules possessing potential anticancer activity are able to inhibit antiapoptotic Bcl-2 family proteins. AT101 (R-(-)-gossypol), a natural BH3-mimetic molecule, has shown anti-tumor activity as a single agent and in combination with standard anticancer therapies in a variety of tumor models. Here, we report the effect of AT101 on apoptosis in cisplatin-resistant ovarian cancer cells and identify the major molecular events that determine sensitivity. AT101 induced cell apoptosis by activating Bax through a conformational change, translocation, and oligomerization. The inhibition of Bax expression only partially prevented caspase-3 cleavage. However, the gene silencing of Bax had no effect on mitochondrial Smac release. Further experiments demonstrated that Smac reduction inhibited caspase-3 activation and attenuated cell apoptosis. More importantly, the inhibition of Smac or overexpression of XIAP attenuated Bax activation in ovarian cells. Furthermore, our data indicate that the Akt-p53 pathway is involved in the regulation of Smac release. Taken together, our data demonstrate the role of Smac and the molecular mechanisms of AT101-induced apoptosis of chemoresistant ovarian cancer cells. Our findings suggest that AT101 not only triggers Bax activation but also induces mitochondrial Smac release. Activated Smac can enhance Bax-mediated cellular apoptosis. Therefore, Smac mediates Bax activation to determine the threshold for overcoming cisplatin resistance in ovarian cancer cells. PMID- 22052904 TI - Solution structure and molecular interactions of lamin B receptor Tudor domain. AB - Lamin B receptor (LBR) is a polytopic protein of the nuclear envelope thought to connect the inner nuclear membrane with the underlying nuclear lamina and peripheral heterochromatin. To better understand the function of this protein, we have examined in detail its nucleoplasmic region, which is predicted to harbor a Tudor domain (LBR-TD). Structural analysis by multidimensional NMR spectroscopy establishes that LBR-TD indeed adopts a classical beta-barrel Tudor fold in solution, which, however, features an incomplete aromatic cage. Removal of LBR-TD renders LBR more mobile at the plane of the nuclear envelope, but the isolated module does not bind to nuclear lamins, heterochromatin proteins (MeCP2), and nucleosomes, nor does it associate with methylated Arg/Lys residues through its aromatic cage. Instead, LBR-TD exhibits tight and stoichiometric binding to the "histone-fold" region of unassembled, free histone H3, suggesting an interesting role in histone assembly. Consistent with such a role, robust binding to native nucleosomes is observed when LBR-TD is extended toward its carboxyl terminus, to include an area rich in Ser-Arg residues. The Ser-Arg region, alone or in combination with LBR-TD, binds both unassembled and assembled H3/H4 histones, suggesting that the TD/RS interface may operate as a "histone chaperone-like platform." PMID- 22052905 TI - Autophagy induced by deficiency of sphingosine-1-phosphate phosphohydrolase 1 is switched to apoptosis by calpain-mediated autophagy-related gene 5 (Atg5) cleavage. AB - Sphingosine 1-phosphate (S1P) and ceramide have been implicated in both autophagy and apoptosis. However, the roles of these sphingolipid metabolites in the links between these two processes are not completely understood. Depletion of S1P phosphohydrolase-1 (SPP1), which degrades intracellular S1P, induces the unfolded protein response and endoplasmic reticulum stress-induced autophagy (Lepine, S., Allegood, J. C., Park, M., Dent, P., Milstien, S., and Spiegel, S. (2011) Cell Death Differ. 18, 350-361). Surprisingly, however, treatment with doxorubicin, which by itself also induced autophagy, markedly reduced the extent of autophagy mediated by depletion of SPP1. Concomitantly, doxorubicin-induced apoptosis was greatly enhanced by down-regulation of SPP1. Autophagy and apoptosis seemed to be sequentially linked because inhibiting autophagy with 3-methyladenine also markedly attenuated apoptosis. Moreover, silencing Atg5 or the three sensors of the unfolded protein response, IRE1alpha, ATF6, and PKR-like eIF2alpha kinase (PERK), significantly decreased both autophagy and apoptosis. Doxorubicin stimulated calpain activity and Atg5 cleavage, which were significantly enhanced in SPP1-depleted cells. Inhibition or depletion of calpain not only suppressed Atg5 cleavage, it also markedly decreased the robust apoptosis induced by doxorubicin in SPP1-deficient cells. Importantly, doxorubicin also increased de novo synthesis of the pro-apoptotic sphingolipid metabolite ceramide. Elevation of ceramide in turn stimulated calpain; conversely, inhibiting ceramide formation suppressed Atg5 cleavage and apoptosis. Hence, doxorubicin switches protective autophagy in SPP1-depleted cells to apoptosis by calpain-mediated Atg5 cleavage. PMID- 22052906 TI - Divalent cation transport by vesicular nucleotide transporter. AB - The vesicular nucleotide transporter (VNUT) is a secretory vesicle protein that is responsible for the vesicular storage and subsequent exocytosis of ATP (Sawada, K., Echigo, N., Juge, N., Miyaji, T., Otsuka, M., Omote, H., and Moriyama, Y. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 5683-5686). Because VNUT actively transports ATP in a membrane potential (Deltapsi)-dependent manner irrespective of divalent cations such as Mg(2+) and Ca(2+), VNUT recognizes free ATP as a transport substrate. However, whether or not VNUT transports chelating complexes with divalent cations remains unknown. Here, we show that proteoliposomes containing purified VNUT actively took up Mg(2+) when ATP was present, as detected by atomic absorption spectroscopy. The VNUT-containing proteoliposomes also took up radioactive Ca(2+) upon imposing Deltapsi (positive inside) but not DeltapH. The Deltapsi-driven Ca(2+) uptake required ATP and a millimolar concentration of Cl(-), which was inhibited by Evans blue, a specific inhibitor of SLC17-type transporters. VNUT in which Arg-119 was specifically mutated to alanine, the counterpart of the essential amino acid residue of the SLC17 family, lost the ability to take up both ATP and Ca(2+). Ca(2+) uptake was also inhibited in the presence of various divalent cations such as Mg(2+). Kinetic analysis indicated that Ca(2+) or Mg(2+) did not affect the apparent affinity for ATP. RNAi of the VNUT gene in PC12 cells decreased the vesicular Mg(2+) concentration to 67.7%. These results indicate that VNUT transports both nucleotides and divalent cations probably as chelating complexes and suggest that VNUT functions as a divalent cation importer in secretory vesicles under physiological conditions. PMID- 22052907 TI - Structural basis of free reduced flavin generation by flavin reductase from Thermus thermophilus HB8. AB - Free reduced flavins are involved in a variety of biological functions. They are generated from NAD(P)H by flavin reductase via co-factor flavin bound to the enzyme. Although recent findings on the structure and function of flavin reductase provide new information about co-factor FAD and substrate NAD, there have been no reports on the substrate flavin binding site. Here we report the structure of TTHA0420 from Thermus thermophilus HB8, which belongs to flavin reductase, and describe the dual binding mode of the substrate and co-factor flavins. We also report that TTHA0420 has not only the flavin reductase motif GDH but also a specific motif YGG in C terminus as well as Phe-41 and Arg-11, which are conserved in its subclass. From the structure, these motifs are important for the substrate flavin binding. On the contrary, the C terminus is stacked on the NADH binding site, apparently to block NADH binding to the active site. To identify the function of the C-terminal region, we designed and expressed a mutant TTHA0420 enzyme in which the C-terminal five residues were deleted (TTHA0420-DeltaC5). Notably, the activity of TTHA0420-DeltaC5 was about 10 times higher than that of the wild-type enzyme at 20-40 degrees C. Our findings suggest that the C-terminal region of TTHA0420 may regulate the alternative binding of NADH and substrate flavin to the enzyme. PMID- 22052908 TI - Origins of specificity and promiscuity in metabolic networks. AB - How enzymes have evolved to their present form is linked to the question of how pathways emerged and evolved into extant metabolic networks. To investigate this mechanism, we have explored the chemical diversity present in a largely unbiased data set of catalytic reactions processed by modern enzymes across the tree of life. In order to get a quantitative estimate of enzyme chemical diversity, we measure enzyme multispecificity or promiscuity using the reaction molecular signatures. Our main finding is that reactions that are catalyzed by a highly specific enzyme are shared by poorly divergent species, suggesting a later emergence of this function during evolution. In contrast, reactions that are catalyzed by highly promiscuous enzymes are more likely to appear uniformly distributed across species in the tree of life. From a functional point of view, promiscuous enzymes are mainly involved in amino acid and lipid metabolisms, which might be associated with the earliest form of biochemical reactions. In this way, results presented in this paper might assist us with the identification of primeval promiscuous catalytic functions contributing to life's minimal metabolism. PMID- 22052909 TI - Structures and interaction analyses of integrin alphaMbeta2 cytoplasmic tails. AB - Integrins are heterodimeric (alpha and beta subunits) signal transducer proteins involved in cell adhesions and migrations. The cytosolic tails of integrins are essential for transmitting bidirectional signaling and also implicated in maintaining the resting states of the receptors. In addition, cytosolic tails of integrins often undergo post-translation modifications like phosphorylation. However, the consequences of phosphorylation on the structures and interactions are not clear. The leukocyte-specific integrin alphaMbeta2 is essential for myeloid cell adhesion, phagocytosis, and degranulation. In this work, we determined solution structures of the myristoylated cytosolic tail of alphaM and a Ser phosphorylated variant in dodecylphosphocholine micelles by NMR spectroscopy. Furthermore, the interactions between non-phosphorylated and phosphorylated alphaM tails with beta2 tail were investigated by NMR and fluorescence resonance energy transfer (FRET). The three-dimensional structures of the 24-residue cytosolic tail of alphaM or phosphorylated alphaM are characterized by an N-terminal amphipathic helix and a loop at the C terminus. The residues at the loop are involved in packing interactions with the hydrophobic face of the helix. 15N-1H heteronuclear single quantum coherence experiments identified residues of alphaM and beta2 tails that may be involved in the formation of a tail-tail heterocomplex. We further examined interactions between myristoylated beta2 tail in dodecylphosphocholine micelles with dansylated alphaM tail peptides by FRET. These studies revealed enhanced interactions between alphaM or phosphorylated alphaM tails with beta2 tail with Kd values ~5.2+/-0.6 and ~4.4+/-0.7 MUm, respectively. Docked structures of tail tail complexes delineated that the alphaM/beta2 interface at the cytosolic region could be sustained by a network of polar interactions, ionic interactions, and/or hydrogen bonds. PMID- 22052910 TI - The vinculin C-terminal hairpin mediates F-actin bundle formation, focal adhesion, and cell mechanical properties. AB - Vinculin is an essential and highly conserved cell adhesion protein, found at both focal adhesions and adherens junctions, where it couples integrins or cadherins to the actin cytoskeleton. Vinculin is involved in controlling cell shape, motility, and cell survival, and has more recently been shown to play a role in force transduction. The tail domain of vinculin (Vt) contains determinants necessary for binding and bundling of actin filaments. Actin binding to Vt has been proposed to induce formation of a Vt dimer that is necessary for cross-linking actin filaments. Results from this study provide additional support for actin-induced Vt self-association. Moreover, the actin-induced Vt dimer appears distinct from the dimer formed in the absence of actin. To better characterize the role of the Vt strap and carboxyl terminus (CT) in actin binding, Vt self-association, and actin bundling, we employed smaller amino terminal (NT) and CT deletions that do not perturb the structural integrity of Vt. Although both NT and CT deletions retain actin binding, removal of the CT hairpin (1061-1066) selectively impairs actin bundling in vitro. Moreover, expression of vinculin lacking the CT hairpin in vinculin knock-out murine embryonic fibroblasts affects the number of focal adhesions formed, cell spreading as well as cellular stiffening in response to mechanical force. PMID- 22052911 TI - Regulation of autophagy by neuropathological protein TDP-43. AB - TDP-43 is a DNA/RNA-binding protein with multicellular functions. As a pathosignature protein of a range of neurodegenerative diseases, TDP-43 is also the major component of the polyubiquitinated inclusions in the pathological cellular samples of these diseases. In normal cells, TDP-43 is processed and degraded by both autophagy and the ubiquitin-proteasome systems. We have found, by microarray hybridization and RT-PCR analyses, that the level of the mRNA encoding the major autophagy component Atg7 is decreased upon depletion of TDP-43 by RNAi knockdown. This decrease of the Atg7 mRNA level could be rescued by overexpression of an siRNA-resistant form of TDP-43, and it appears to be the result of destabilization of the Atg7 mRNA, to which TDP-43 could bind through its RNA recognition motif 1 domain. Furthermore, depletion of TDP-43 with the consequent loss of the Atg7 mRNA/ATG7 protein causes impairment of the autophagy and facilitates the accumulation of polyubiquitinated proteins as well as the autophagy/ubiquitin-proteasome system substrate p62 in the cells. These data demonstrate the function of TDP-43 as a maintenance factor of the autophagy system, and they suggest the existence of a feedback regulatory loop between TDP 43 and autophagy. A scenario in which loss of function of TDP-43 contributes to the development of TDP-43 proteinopathies is presented. PMID- 22052912 TI - Augmented phosphorylation of cardiac troponin I in hypertensive heart failure. AB - An altered cardiac myofilament response to activating Ca(2+) is a hallmark of human heart failure. Phosphorylation of cardiac troponin I (cTnI) is critical in modulating contractility and Ca(2+) sensitivity of cardiac muscle. cTnI can be phosphorylated by protein kinase A (PKA) at Ser(22/23) and protein kinase C (PKC) at Ser(22/23), Ser(42/44), and Thr(143). Whereas the functional significance of Ser(22/23) phosphorylation is well understood, the role of other cTnI phosphorylation sites in the regulation of cardiac contractility remains a topic of intense debate, in part, due to the lack of evidence of in vivo phosphorylation. In this study, we utilized top-down high resolution mass spectrometry (MS) combined with immunoaffinity chromatography to determine quantitatively the cTnI phosphorylation changes in spontaneously hypertensive rat (SHR) model of hypertensive heart disease and failure. Our data indicate that cTnI is hyperphosphorylated in the failing SHR myocardium compared with age matched normotensive Wistar-Kyoto rats. The top-down electron capture dissociation MS unambiguously localized augmented phosphorylation sites to Ser(22/23) and Ser(42/44) in SHR. Enhanced Ser(22/23) phosphorylation was verified by immunoblotting with phospho-specific antibodies. Immunoblot analysis also revealed up-regulation of PKC-alpha and -delta, decreased PKCepsilon, but no changes in PKA or PKC-beta levels in the SHR myocardium. This provides direct evidence of in vivo phosphorylation of cTnI-Ser(42/44) (PKC-specific) sites in an animal model of hypertensive heart failure, supporting the hypothesis that PKC phosphorylation of cTnI may be maladaptive and potentially associated with cardiac dysfunction. PMID- 22052913 TI - Structure of myostatin.follistatin-like 3: N-terminal domains of follistatin-type molecules exhibit alternate modes of binding. AB - TGF-beta family ligands are involved in a variety of critical physiological processes. For instance, the TGF-beta ligand myostatin is a staunch negative regulator of muscle growth and a therapeutic target for muscle-wasting disorders. Therefore, it is important to understand the molecular mechanisms of TGF-beta family regulation. One form of regulation is through inhibition by extracellular antagonists such as the follistatin (Fst)-type proteins. Myostatin is tightly controlled by Fst-like 3 (Fstl3), which is the only Fst-type molecule that has been identified in the serum bound to myostatin. Here, we present the crystal structure of myostatin in complex with Fstl3. The structure reveals that the N terminal domain (ND) of Fstl3 interacts uniquely with myostatin as compared with activin A, because it utilizes different surfaces on the ligand. This results in conformational differences in the ND of Fstl3 that alter its position in the type I receptor-binding site of the ligand. We also show that single point mutations in the ND of Fstl3 are detrimental to ligand binding, whereas corresponding mutations in Fst have little effect. Overall, we have shown that the NDs of Fst type molecules exhibit distinctive modes of ligand binding, which may affect overall affinity of ligand.Fst-type protein complexes. PMID- 22052914 TI - Inhibition of miR-15 protects against cardiac ischemic injury. AB - RATIONALE: Myocardial infarction (MI) is a leading cause of death worldwide. Because endogenous cardiac repair mechanisms are not sufficient for meaningful tissue regeneration, MI results in loss of cardiac tissue and detrimental remodeling events. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression in a sequence dependent manner. Our previous data indicate that miRNAs are dysregulated in response to ischemic injury of the heart and actively contribute to cardiac remodeling after MI. OBJECTIVE: This study was designed to determine whether miRNAs are dysregulated on ischemic damage in porcine cardiac tissues and whether locked nucleic acid (LNA)-modified anti-miR chemistries can target cardiac expressed miRNAs to therapeutically inhibit miR-15 on ischemic injury. METHODS AND RESULTS: Our data indicate that the miR-15 family, which includes 6 closely related miRNAs, is regulated in the infarcted region of the heart in response to ischemia-reperfusion injury in mice and pigs. LNA-modified chemistries can effectively silence miR-15 family members in vitro and render cardiomyocytes resistant to hypoxia-induced cardiomyocyte cell death. Correspondingly, systemic delivery of miR-15 anti-miRs dose-dependently represses miR-15 in cardiac tissue of both mice and pigs, whereas therapeutic targeting of miR-15 in mice reduces infarct size and cardiac remodeling and enhances cardiac function in response to MI. CONCLUSIONS: Oligonucleotide-based therapies using LNA-modified chemistries for modulating cardiac miRNAs in the setting of heart disease are efficacious and validate miR-15 as a potential therapeutic target for the manipulation of cardiac remodeling and function in the setting of ischemic injury. PMID- 22052915 TI - Activating transcription factor 1 directs Mhem atheroprotective macrophages through coordinated iron handling and foam cell protection. AB - RATIONALE: Intraplaque hemorrhage (IPH) drives atherosclerosis through the dual metabolic stresses of cholesterol-enriched erythrocyte membranes and pro-oxidant heme/iron. When clearing tissue hemorrhage, macrophages are typically seen storing either iron or lipid. We have recently defined hemorrhage-associated macrophages (HA-mac) as a plaque macrophage population that responds adaptively to IPH. OBJECTIVE: This study aimed to define the key transcription factor(s) involved in HO-1 induction by heme. METHODS AND RESULTS: To address this question, we used microarray analysis and transfection with siRNA and plasmids. To maintain physiological relevance, we focused on human blood-derived monocytes. We found that heme stimulates monocytes through induction of activating transcription factor 1 (ATF-1). ATF-1 coinduces heme oxygenase-1 (HO-1) and Liver X receptor beta (LXR-beta). Heme-induced HO-1 and LXR-beta were suppressed by knockdown of ATF-1, and HO-1 and LXR-beta were induced by ATF-1 transfection. ATF 1 required phosphorylation for full functional activity. Expression of LXR-beta in turn led to induction of other genes central to cholesterol efflux, such as LXR-alpha and ABCA1. This heme-directed state was distinct from known macrophage states (M1, M2, Mox) and, following the same format, we have designated them Mhem. CONCLUSIONS: These results show that ATF-1 mediates HO-1 induction by heme and drives macrophage adaptation to intraplaque hemorrhage. Our definition of an ATF-1-mediated pathway for linked protection from foam cell formation and oxidant stress may have therapeutic potential. PMID- 22052916 TI - Mitochondrial fusion is essential for organelle function and cardiac homeostasis. AB - RATIONALE: Mitochondria constitute 30% of myocardial mass. Mitochondrial fusion and fission appear essential for health of most tissues. Mitochondrial fission occurs in neonatal cardiomycyte and is implicated in cardiomyocyte death. Mitochondrial fusion has not been observed in postmitotic myocytes of adult hearts, and its occurrence and function in this context are controversial. OBJECTIVE: Determine the consequences on organelle and organ function of disrupting cardiomyocyte mitochondrial fusion in vivo. METHODS AND RESULTS: The murine mfn1 and mfn2 genes, encoding mitofusins (Mfn) 1 and 2 that mediate mitochondrial tethering and outer mitochondrial membrane fusion, were interrupted by Cre-mediated excision of essential exons in neonatal (Nkx2.5-Cre) and adult (MYH6 modified estrogen receptor-Cre-modified estrogen receptor plus tamoxifen or Raloxifene) hearts. Embryonic combined Mfn1/Mfn2 ablation was lethal after e9.5. Conditional combined Mfn1/Mfn2 ablation in adult hearts induced mitochondrial fragmentation, cardiomyocyte and mitochondrial respiratory dysfunction, and rapidly progressive and lethal dilated cardiomyopathy. Before heart failure developed, cardiomyocyte shortening and calcium cycling were unaffected by absence of Mfn1 and Mfn2. Based on the time course over which fusion-defective mitochondrial size decreases, a mitochondrial fusion/fission cycle in adult mouse hearts occurs approximately every 16 days. CONCLUSIONS: Mitochondrial fusion in adult cardiac myocytes is necessary to maintain normal mitochondrial morphology and is essential for normal cardiac respiratory and contractile function. Interruption of mitochondrial fusion causes lethal cardiac failure at a time corresponding to 3 or 4 cycles of unopposed mitochondrial fission. PMID- 22052917 TI - Adventitial delivery of an allogeneic bone marrow-derived adherent stem cell in acute myocardial infarction: phase I clinical study. AB - RATIONALE: MultiStem is an allogeneic bone marrow-derived adherent adult stem cell product that has shown efficacy in preclinical models of acute myocardial infarction (AMI). In this phase I clinical trial in patients with first ST elevation-myocardial infarction (STEMI), we combine first-in-man delivery of MultiStem with a first-in-coronary adventitial delivery system to determine the effects of this system on left ventricular function at 4 months after AMI. OBJECTIVE: Test the effects of adventitial delivery of Multistem in the peri infarct period in patients with first STEMI. METHODS AND RESULTS: This study was a phase I, open-label, dose-escalating registry control group study. Nineteen patients received MultiStem (20 million, n=6; 50 million, n=7; or 100 million, n=6) and 6 subjects were assigned to the registry control group. Two to 5 days after AMI, we delivered MultiStem to the adventitia of the infarct-related vessel in patients with first-time STEMI. All patients underwent primary percutaneous coronary intervention with resulting Thrombolysis In Myocardial Infarction grade 3 flow and with ejection fraction (EF) <=45% as determined by echocardiogram or left ventriculogram within 12 hours of primary percutaneous coronary intervention. The cell product (20 million, 50 million, or 100 million) was well tolerated, and no serious adverse events were deemed related to MultiStem. There was no increase in creatine kinase-MB or troponin associated with the adventitial delivery of MultiStem. In patients with EF determined to be <=45% by a core laboratory within 24 hours before the MultiStem injection, we observed a 0.9 (n=4), 3.9 (n=4), 13.5 (n=5), and 10.9 (n=2) percent absolute increases in EF in the registry, 20 million, 50 million, and 100 million dose groups, respectively. The increases in EF in the 50 million and 100 million groups were accompanied by 25.4 and 8.4 mL increases in left ventricular stroke volume. CONCLUSIONS: In this study, the delivery of MultiStem to the myocardium in patients with recent STEMI was well tolerated and safe. In patients who exhibited significant myocardial damage, the delivery of >=50 million MultiStem resulted in improved EF and stroke volume 4 months later. These findings support further development of MultiStem in patients with AMI and they validate the potential of a system for delivery of adult stem cells at any time after primary percutaneous coronary intervention. PMID- 22052918 TI - Chair's summary: pulmonary circulation in health and disease. PMID- 22052919 TI - Functional and molecular heterogeneity of pulmonary endothelial cells. AB - In recent years there has been an increasing appreciation of the functional heterogeneity that exists between extraalveolar and alveolar endothelial cells. One of the most striking features of pulmonary microvascular endothelial cells is that they possess a highly impermeable barrier with respect to pulmonary artery or vein endothelial cells. This cellular feature is observed in culture and in the intact microcirculation, prompting a reevaluation of the key physiological principles that control permeability and the fate of fluid (or exudate) once it leaves the circulation. Pulmonary microvascular endothelial cells express calcium channels not found in extraalveolar endothelial cells, including the vanilloid family transient receptor potential 4 channel and the alpha1G T-type calcium channel. Whereas activation of the TRPV4 channel causes alveolar flooding, activation of the alpha1G T-type calcium channel promotes P-selectin surface translocation, events specific to the microcirculation. Although endothelium is an attractive therapeutic target in acute lung injury and other vascular disorders, the growing awareness of pulmonary endothelial cell heterogeneity increasingly suggests that a panendothelial cell approach is suboptimal. Rather, development of novel therapeutics based upon anatomically restricted expression of molecular signatures may be developed to better combat vascular disease. PMID- 22052920 TI - Real-time imaging assessment of pulmonary vascular responses. AB - Real-time imaging of the intact lung allows for the visualization and analysis of pulmonary vascular responses at a unique spatial and temporal resolution. For visual access to the pulmonary microvasculature under closed chest conditions, a series of thoracic window techniques has been developed. These approaches provide singular insights into basic physiological phenomena, such as capillary recruitment and hypoxic pulmonary vasoconstriction, and into the site, extent, and mechanisms of neutrophil margination in the pulmonary vasculature. Recent advancements, such as the murine thoracic window model and the oxygen saturation mapping technique, have expanded these applications to studies in genetically modified animals and to the analysis of regional gas exchange. Although intravital microscopy may visualize vascular responses in their most physiologic context, functional imaging in isolated perfused lungs allows for targeting of individual cell subsets with functional fluorescence probes and specific interventions. This approach has proven essential for studies on the spatial arrangement and trafficking of cytoskeletal proteins such as actin, organelles such as mitochondria, or vesicles such as Weibel-Palade bodies in lung endothelial cells. Functional imaging has generated unprecedented insights into the temporal and spatial profile of intra- and subcellular second messenger systems, including signaling cascades via Ca(2+), nitric oxide, or reactive oxygen species. The rapid advancement of bioimaging capabilities at the technical level, the increasing availability of protein-based fluorescent probes, and the ongoing refinement of in vivo and ex vivo lung models provide promising prospects for the application of real-time bioimaging to the further resolution of pulmonary vascular responses in lung health and disease. PMID- 22052921 TI - Progenitor cells in the pulmonary circulation. AB - The mechanisms involved in the regulation of pulmonary vascular endothelial cells to replace aged or injured cells remains poorly understood, although differences in proliferative potential between the microvascular and macrovascular endothelium are well described. The presence of resident pulmonary vascular endothelial progenitor cells in rats and mice has been recently reported. These resident endothelial progenitor cells display clonal proliferative potential, restricted expression of cell surface molecules to those typical of lung endothelium, and in vivo vessel-forming ability upon transplantation into recipient animals. The rat pulmonary microvascular endothelium is enriched in resident progenitor cells, with the highest proliferative potential compared with the pulmonary macrovascular endothelium. Preliminary evidence suggests that resident endothelial progenitor cells are present in the human lung vasculature, but whether differences in enrichment of the progenitors in various pulmonary vascular beds exist remains to be determined. PMID- 22052922 TI - Pulmonary vascular innervation and its role in responses to hypoxia: size matters! AB - The pulmonary vasculature is innervated by specific subsets of sympathetic, parasympathetic, and sensory nerve fibers. In contrast to most other organs, innervation density is highest at large-caliber vessels and decreases toward the periphery, and reactivity to vasoactive compounds also changes along the course. In some species, such as the experimentally widely used rodents rat and mouse, autonomic efferent (sympathetic and parasympathetic) perivascular axons barely reach beyond the lung hilus, whereas in humans this innervation extends to small intrapulmonary vessels. Throughout, the most distal arterioles (i.e., intraacinar arteries equipped with an incomplete coat of intermediate cells instead of a full muscular wall) are devoid of innervation. Altogether, 10 vasoactive substances (3 small molecular transmitters and 7 neuropeptides) at minimum have been identified in various combinations (cotransmission) in pulmonary vascular axons. Analysis of this "neurochemical coding" has been provided only for the guinea pig so far, but not for humans or for animal species commonly used for pulmonary vascular research. Sympathetic pulmonary vascular neurons are reflexively activated via arterial chemoreceptors when arterial Po(2) is lowered and adapt the pulmonary vasculature to this condition of increased pulmonary blood flow by alpha(1) adrenoreceptor-mediated increase in vascular impedance primarily at large vessels. In contrast, neither they nor other nerve fibers play a role in the local hypoxic vasoconstriction triggered by low alveolar Po(2), which serves to match perfusion to ventilation. The major potential role of the pulmonary vascular innervation, autonomic and sensory, lies in the pronounced trophic activities of its transmitters. PMID- 22052923 TI - Lung cell hypoxia: role of mitochondrial reactive oxygen species signaling in triggering responses. AB - Lung cells experience hypoxia during development, during travel to high altitude, and in acute and chronic lung diseases. The functional responses evoked by hypoxia are diverse and generally act to protect the cells from hypoxic injury, although some lung cell responses are counterproductive because they degrade normal function of the organ. The cellular O(2) sensor responsible for many of these responses involves the mitochondrial electron transport chain. Under hypoxic conditions, increased release of reactive oxygen species from the inner mitochondrial membrane to the intermembrane space leads to the activation of transcription factors, including hypoxia-inducible factor, activation of hypoxic pulmonary vasoconstriction, activation of AMP-dependent protein kinase, and internalization of the membrane Na,K-ATPase from the basolateral membrane of alveolar epithelial cells. Although the specific targets of reactive oxygen species signals are not fully understood, this signaling pathway is critical for development and for normal lung responses in the newborn and the mature lung. PMID- 22052924 TI - Stress responses affecting homeostasis of the alveolar capillary unit. AB - The maintenance of the alveolar structure is required throughout life. To accomplish this goal, alveolar cells, including endothelial, epithelial, and fibroblastic cells, provide key molecules with broad survival and antiapoptotic effects. These complex interactions are disrupted by cigarette smoke, leading to emphysema. Smoke imposes an environmental stress to the lung with the activation of "sensor-like" molecular signaling. Activation of RTP801, leading to mTOR inhibition, is paradigmatic of these responses. The accumulation of cellular damage, with the generation of endogenous mediators of inflammation, may proceed toward an aging phenotype. These alterations may impose significant challenges to cell-based regenerative or pharmacological therapies. PMID- 22052925 TI - Involvement of ceramide in cell death responses in the pulmonary circulation. AB - Ceramides are signaling sphingolipids involved in cellular homeostasis but also in pathological processes such as unwanted apoptosis, growth arrest, oxidative stress, or senescence. Several enzymatic pathways are responsible for the synthesis of ceramides, which can be activated in response to exogenous stimuli such as cytokines, radiation, or oxidative stress. Endothelial cells are particularly rich in acid sphingomyelinases, which can be rapidly activated to produce ceramides, both intracellular and at the plasma membrane. In addition, neutral sphingomyelinases, the de novo pathway and the ceramide recycling pathway, may generate excessive ceramides involved in endothelial cell responses. When up-regulated, ceramides trigger signaling pathways that culminate in endothelial cell death, which in murine lungs has been linked to the development of emphysema-like disease. Furthermore, ceramides may be released paracellularly where they are believed to exert paracrine activities. Such effects, along with ceramides released by inflammatory mediators, may contribute to lung inflammation and pulmonary edema, because ceramide-challenged pulmonary endothelial cells exhibit decreased barrier function, independent of apoptosis. Reestablishing the sphingolipid homeostasis, either by modulating ceramide synthesis or by opposing its biological effects through augmentation of the prosurvival sphingosine-1 phosphate, may alleviate acute or chronic pulmonary conditions characterized by vascular endothelial cell death or dysfunction. PMID- 22052926 TI - Blocking NF-kappaB: an inflammatory issue. AB - The nuclear factor (NF)-kappaB is considered the master regulator of inflammatory responses. Studies in mouse models have established this transcription factor as an important mediator of many inflammatory disease states, including pulmonary diseases such as acute lung injury and acute respiratory distress syndrome. Endothelial cells provide the first barrier for leukocytes migrating to the inflamed sites and hence offer an attractive cellular context for targeting NF kappaB for treatment of these diseases. However, recent studies showing that NF kappaB also plays an important role in resolution phase of inflammation and in tissue repair and homeostasis have challenged the view of therapeutic inhibition of NF-kappaB. This article reviews the regulation of NF-kappaB in the context of endothelial cell signaling and provides a perspective on why "dampening" rather than "abolishing" NF-kappaB activation may be a safe and effective treatment strategy for inflammation-associated pulmonary and other inflammatory diseases. PMID- 22052927 TI - Dynamics of airway blood vessels and lymphatics: lessons from development and inflammation. AB - Blood vessels and lymphatic vessels in the respiratory tract play key roles in inflammation. By undergoing adaptive remodeling and growth, blood vessels undergo changes that enable the extravasation of plasma and leukocytes into inflamed tissues, and lymphatic vessels adjust to the increased fluid clearance and cell traffic involved in immune responses. Blood vessels and lymphatics in adult airways are strikingly different from those of late-stage embryos. Before birth, blood vessels in mouse airways make up a primitive plexus similar to that of the yolk sac. This plexus undergoes rapid and extensive remodeling at birth. In the early neonatal period, parts of the plexus regress. Capillaries then rapidly regrow, and with arterioles and venules form the characteristic adult vascular pattern. Lymphatic vessels of the airways also undergo rapid changes around birth, when lymphatic endothelial cells develop button-like intercellular junctions specialized for efficient fluid uptake. Among the mechanisms that underlie the onset of rapid vascular remodeling at birth, changes in tissue oxygen tension and mechanical forces associated with breathing are likely to be involved, along with growth factors that promote the growth and maturation of blood vessels and lymphatics. Whatever the mechanisms, the dynamic nature of airway blood vessels and lymphatics during perinatal development foretells the extraordinary vascular plasticity found in many diseases. PMID- 22052928 TI - Vascular endothelial growth factor and vascular homeostasis. AB - Vascular endothelial growth factor (VEGF) is the angiogenic factor promoting and orchestrating most, if not all, processes of neovascularization taking place in the embryo and the adult. VEGF is also required to sustain newly formed vessels and plays additional multiple roles in the maintenance and function of certain mature vascular beds. Correspondingly, perturbations in VEGF signaling may impact organ homeostasis in multiple ways. Here we briefly review potential consequences of VEGF loss of function in adult organs. Different vascular beds display highly variable dependencies on VEGF for survival, and its loss of function may trigger the regression of many VEGF-dependent vasculatures. Normal turnover of blood vessels, in conjunction with the fact that VEGF is indispensable for compensatory angiogenesis to restore adequate perfusion, accounts for progressive vascular rarefaction under conditions of chronic VEGF inhibition of even vasculatures that are not intrinsically dependent on VEGF. Because blood vessels may have paracrine functions other than their traditional role in tissue perfusion, vascular regression resulting from VEGF withdrawal may cause substantial collateral tissue damage. VEGF may also impact tissue homeostasis via acting directly on nonvascular cells expressing cognate receptors. In the particular case of the lung, constitutive abundant expression of VEGF together with the fact that its receptors are distributed on both endothelial and epithelial cells is compatible with multiple homeostatic VEGF functions in the adult lung. Indeed, experimental inhibition of VEGF in the mature lung produces lesions resembling common lung pathologies, including emphysema and respiratory distress syndrome. PMID- 22052929 TI - Studies of vascular endothelial growth factor in asthma and chronic obstructive pulmonary disease. AB - Vascular endothelial growth factor (VEGF) is a potent stimulator of vascular angiogenesis, permeability, and remodeling that also plays important roles in wound healing and tissue cytoprotection. To begin to define the roles of VEGF in diseases like asthma and COPD, we characterized the effects of lung-targeted transgenic VEGF(165) and defined the innate immune pathways that regulate VEGF tissue responses. The former studies demonstrated that VEGF plays an important role in Th2 inflammation because, in addition to stimulating angiogenesis and edema, VEGF induced eosinophilic inflammation, mucus metaplasia, subepithelial fibrosis, myocyte hyperplasia, dendritic cell activation, and airways hyperresponsiveness via IL-13-dependent and -independent mechanisms. VEGF was also produced at sites of aeroallergen-induced Th2 inflammation, and VEGF receptor blockade ameliorated adaptive Th2 inflammation and Th2 cytokine elaboration. The latter studies demonstrated that activation of the RIG-like helicase (RLH) innate immune pathway using viral pathogen-associated molecular patterns such as Poly(I:C) or viruses ameliorated VEGF-induced tissue responses. In accord with these findings, Poly(I:C)-induced RLH activation also abrogated aeroallergen-induced Th2 inflammation. When viewed in combination, these studies suggest that VEGF excess can contribute to the pathogenesis of Th2 inflammatory disorders such as asthma and that abrogation of VEGF signaling via RLH activation can contribute to the pathogenesis of viral disorders such as virus-induced COPD exacerbations. They also suggest that RLH activation may be a useful therapeutic strategy in asthma and related disorders. PMID- 22052930 TI - Pulmonary microcirculation in interstitial lung disease. AB - Vascular abnormalities are a common feature of interstitial lung diseases (ILD). The development of pulmonary hypertension has been recognized as a condition that determines the overall prognosis, particularly for patients with idiopathic pulmonary fibrosis and scleroderma-associated lung disease. The treatment of chronic ILD is challenging due to the lack of causal therapies, specifically of the fibroproliferative component of the disorders, but also due to the vascular abnormalities. Recent studies suggest that the pathobiology underlying the remodeling and fibrosis of the parenchyma in ILD and the mechanisms leading to structural and functional alteration of the pulmonary vasculature are closely intertwined. This review summarizes the current understanding of the pathobiology of the microcirculation in ILD, with a specific focus on idiopathic pulmonary fibrosis and scleroderma-associated lung disease. An improved understanding of the complex biological mechanisms that link alveolar interstitial and vascular remodeling in chronic ILD will be required to identify novel drug targets. PMID- 22052932 TI - Vascular progenitor cells in chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is commonly associated with vascular changes in the pulmonary and systemic circulations. Pulmonary muscular arteries characteristically show intimal hyperplasia, which is produced in part by the proliferation of poorly differentiated smooth muscle cells. The origin of these cells has not been determined. Bone marrow has the capacity to produce and mobilize progenitor cells that may be recruited at sites of vascular damage and contribute to vascular repair through their differentiation into endothelial cells. Nevertheless, under some circumstances bone marrow-derived progenitor cells may migrate into the intima and differentiate into smooth muscle cells. Local factors and cell-to-cell contact are critical in determining the fate of progenitor cells in the vessel wall. Studies assessing the number of circulating bone marrow-derived vascular progenitor cells indicate that COPD is characterized by a reduction in circulating hemopoietic and vascular progenitors. The mechanisms of this reduction have not been elucidated. It has been suggested that this process may lead to reduced vascular repair capacity and increase the risk of cardiovascular complications, which are associated with significant morbidity and mortality in COPD. Further investigation in this field and elucidation of the underlying mechanisms will contribute to a better management of this major complication of COPD. PMID- 22052931 TI - The epidemiology of vascular dysfunction relating to chronic obstructive pulmonary disease and emphysema. AB - Cor pulmonale has long been described in very severe chronic obstructive pulmonary disease (COPD) and emphysema. Cross-sectional results from population based studies show that left ventricular filling and a variety of vascular measures in the systemic circulation are abnormal in preclinical COPD and emphysema and that a predominant vascular change in COPD and emphysema is endothelial and microvascular dysfunction. These findings suggest that pulmonary vascular changes may occur early in COPD and emphysema and might contribute to pathogenesis. However, longitudinal epidemiologic studies with direct measures of the pulmonary vasculature are lacking; therefore, inferences are limited at present. New imaging-based approaches to the assessment of the pulmonary vasculature are applicable to epidemiologic studies and may help in defining the relationship of pulmonary vascular damage to progression of COPD and emphysema. These measures may also provide imaging-based surrogate markers, and novel therapeutics targeted to the pulmonary vasculature might reduce symptoms and improve function in these common diseases. PMID- 22052933 TI - Cell-based therapies for lung vascular diseases: lessons for the future. AB - Pulmonary arterial hypertension or acute respiratory distress syndrome (ARDS) represent diseases caused in large part by lung endothelial injury and inflammation. Pulmonary arterial hypertension is a progressive and debilitating lung disorder, which is characterized by hallmark pathological features in the small peripheral pulmonary arteries, including intimal hyperplasia and fibrosis, medial hypertrophy, increased deposition of extracellular matrix, infiltration of inflammatory mediators, and in many instances of advanced disease, plexiform lesions. ARDS is a clinically important complication of severe acute lung injury and a significant cause of morbidity and mortality in critically ill patients. Acute lung injury/ARDS is characterized by breakdown of the air-blood barrier, with the accumulation of proteinaceous fluid and influx of inflammatory cells into the alveolar airspace, all of which are likely mediated by endothelial dysfunction and disruption of the pulmonary endothelial barrier. Preclinical studies suggest that cellular therapies may offer unique and effective alternatives for respiratory diseases that currently have limited (or no) treatment options. Encouraging results from studies using progenitor or mesenchymal stem cells suggest that these cells may exert their therapeutic benefits by promoting vascular repair and regeneration and/or by modulating the pathological immune responses. Furthermore, by combining genetic engineering with cell therapy, it may be possible to enhance the regenerative function of these cells, particularly in the context of adult autologous cell therapy, and therefore provide additional benefits that may overcome many of the limitations of cell or gene therapy alone. PMID- 22052934 TI - AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and other Atherosclerotic Vascular Disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation. PMID- 22052935 TI - Displaced ovarian granulosa cells mimicking metastatic lobular carcinoma of the breast. PMID- 22052936 TI - Two cases of opportunistic parasite infections in patients receiving alemtuzumab. AB - Two cases are reported of rare digestive opportunistic parasites in patients being treated with alemtuzumab for lymphoid haematological malignancies. In both patients, classical biological examinations were insufficient to reach the diagnosis. Only specific parasitological techniques enabled diagnoses of cryptosporidiosis and microsporidiosis, respectively. In both cases, cellular immune reconstitution was sufficient to eradicate these opportunistic infections. In this context, parasitological diagnosis is often underestimated by medical practitioners, so immunologists and oncohaematologists need to be aware of this kind of opportunistic pathogen. PMID- 22052937 TI - Iron deprivation suppresses hepatocellular carcinoma growth in experimental studies. AB - PURPOSE: Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death, and iron overload is a significant risk factor in the development of HCC. In this study, we investigated the potential application of depriving iron by a novel iron chelator, thiosemicarbazone-24 (TSC24), in HCC treatment. EXPERIMENTAL DESIGN: Two HCC cell lines and HFE knockout (HFE(-/-)) mice were used to determine iron chelation efficiency of TSC24. The anticancer effects of TSC24 on HCC were analyzed in vitro and in athymic xenograft mouse models. RESULTS: Treatment with TSC24 significantly decreased the cellular iron concentration in hepatoma cells and the serum iron concentration in HFE(-/-) mice by blocking iron uptake and interfering with normal regulation of iron levels. Moreover, the viability of HCC cell lines was reduced by TSC24. Confirming the mechanism of the agent, this decrease in viability could be partially rescued by addition of exogenous iron. TSC24 also suppressed tumor growth in athymic mice bearing human HCC xenografts in a concentration-dependent manner, without apparent toxicity in parallel with a decrease in the serum iron level. Further studies revealed that TSC24 efficiently triggered cell-cycle arrest and apoptosis in Hep3B and HepG2 cell lines. CONCLUSIONS: TSC24 is a potent iron chelator that suppresses human HCC tumor growth by disrupting iron homeostasis, reducing available iron, and triggering cell-cycle arrest and apoptosis, without apparent host toxicity at effective doses. Thus, TSC24 shows great potential for the treatment of HCC. PMID- 22052938 TI - Epidemiological transition in a rural community of northern India: 18-year mortality surveillance using verbal autopsy. AB - BACKGROUND: Information on causes of death is vital for planning of health services. However, vital events registration systems are weak in developing countries. Therefore, verbal autopsy (VA) tools were incorporated in a community based surveillance system to track causes of death. METHOD AND FINDINGS: Trained fieldworker identified all deaths and interviewed a living relative of those who had died during 1992-2009, using VA, in eight villages of Haryana (11,864 populations). These field reports detailing events preceding death were reviewed by two trained physicians, who independently assigned an International Classification of Disease-10 code to each death. Discrepancies were resolved through reconciliation and, if necessary, adjudication. Non-communicable conditions were the leading causes of death (47.6%) followed by communicable diseases including maternal, perinatal and nutritional conditions (34.0%), and injuries (11.4%). Cause of death could not be determined in 6.9% cases. Deaths due to cardiovascular diseases showed a significant rise, whereas deaths due to diarrhoeal diseases have declined (p<0.01). Majority (90.0%) of the deceased had contacted a healthcare provider during illness but only 11.5% were admitted in hospital before death. CONCLUSION: Rising trend of cardiovascular diseases observed in a rural community of Haryana in India calls for reorientation of rural healthcare delivery system for prevention and control of chronic diseases. PMID- 22052939 TI - Nonhematopoietically derived DNA is shorter than hematopoietically derived DNA in plasma: a transplantation model. AB - BACKGROUND: Plasma DNA is predominantly hematopoietic in origin. The size difference between maternal- and fetal-derived DNA in maternal plasma prompted us to investigate whether there was any discrepancy in molecular size between hematopoietically and nonhematopoietically derived DNA in plasma. METHODS: Plasma DNA samples from 6 hematopoietic stem cell transplant recipients and 1 liver transplant recipient were analyzed by massively parallel paired-end sequencing. The size of each fragment was deduced from the alignment positions of the paired reads. In sex-mismatched transplant recipients, the reads from chromosome Y were used as markers for the male donor/recipient. For other transplant recipients, the reads of the donor- and recipient-specific alleles were identified from the single-nucleotide polymorphism genotypes. RESULTS: In male patients receiving female hematopoietic stem cells, more chromosome Y-derived DNA molecules (nonhematopoietically derived) were <=150 bp than the autosome-derived ones (mainly hematopoietically derived) (median difference, 9.9%). In other hematopoietic stem cell transplant recipients, more recipient-specific DNA molecules (nonhematopoietically derived) were <=150 bp than the donor-specific ones (hematopoietically derived) (median difference, 14.8%). In the liver transplant recipient, more donor-derived DNA molecules (liver derived) were <=150 bp than the recipient-derived ones (mainly hematopoietically derived) (difference, 13.4%). The nonhematopoietically derived DNA exhibited a reduction in a 166-bp peak compared with the hematopoietically derived DNA. A 10-bp periodicity in size distribution below approximately 143 bp was observed in both DNA populations. CONCLUSIONS: Massively parallel sequencing is a powerful tool for studying posttransplantation chimerism. Plasma DNA molecules exhibit a distinct fragmentation pattern, with the nonhematopoietically derived molecules being shorter than the hematopoietically derived ones. PMID- 22052940 TI - Crystal structure of the predicted phospholipase LYPLAL1 reveals unexpected functional plasticity despite close relationship to acyl protein thioesterases. AB - Sequence homology indicates the existence of three human cytosolic acyl protein thioesterases, including APT1 that is known to depalmitoylate H- and N-Ras. One of them is the lysophospholipase-like 1 (LYPLAL1) protein that on the one hand is predicted to be closely related to APT1 but on the other hand might also function as a potential triacylglycerol lipase involved in obesity. However, its role remained unclear. The 1.7 A crystal structure of LYPLAL1 reveals a fold very similar to APT1, as expected, but features a shape of the active site that precludes binding of long-chain substrates. Biochemical data demonstrate that LYPLAL1 exhibits neither phospholipase nor triacylglycerol lipase activity, but rather accepts short-chain substrates. Furthermore, extensive screening efforts using chemical array technique revealed a first small molecule inhibitor of LYPLAL1. PMID- 22052941 TI - Effect of single post-ovulatory administration of levonorgestrel on gene expression profile during the receptive period of the human endometrium. AB - The hypothesis that levonorgestrel (LNG) used as an emergency contraceptive interferes with endometrial receptivity remains unproven. We compared the endometrial gene expression profile during the receptive period after administering a single dose of LNG 1.5 mg or placebo on day 1 of the luteal phase. An endometrial biopsy was done on day LH+7 or LH+8 and samples were taken from seven volunteers, each one contributing with one cycle treated with placebo and another with LNG. The expression of 20 383 genes was determined using cDNA microarrays. Real-time RT-PCR was used 1) to confirm the differences found in DNA microarray analysis and 2) to determine the effect of LNG on transcript levels of C3, C4BPalpha, COX2, MAOA, S100A4, and SERPINB9, known to be upregulated during receptivity, and on cPLA2alpha, JAK1, JNK1, CTSL1, and GSTP1, known to respond to mifepristone. Additional endometrial biopsies were done during the pre-receptive (LH+3) and receptive (LH+7) period and samples were taken from eight untreated volunteers in order to determine the changes associated with acquisition of receptivity of 14 genes. Mean levels of PAEP, TGM2, CLU, IGF2, and IL6ST mRNAs increased after administering LNG while those of HGD, SAT1, EVA1, LOC90133, ANXA1, SLC25A29, CYB5A, CRIP1, and SLC39A14 decreased. Except for the level of ANXA1 transcript, all changes remained within the range observed in untreated controls, and none of the transcripts responding to mifepristone changed in response to LNG. Post-ovulatory administration of LNG caused minimal changes in gene expression profiling during the receptive period. Neither the magnitude nor the nature or direction of the changes endorses the hypothesis that LNG interferes with endometrial receptivity. PMID- 22052942 TI - Dialysate sodium concentration and the association with interdialytic weight gain, hospitalization, and mortality. AB - BACKGROUND AND OBJECTIVES: Recommendations to decrease the dialysate sodium (DNa) prescription demand analyses of patient outcomes. We analyzed morbidity and mortality at various levels of DNa, simultaneously accounting for interdialytic weight gain (IDWG) and for the mortality risk associated with lower predialysis serum sodium (SNa) levels. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used multiply-adjusted linear mixed models to evaluate the magnitude of IDWG and Cox proportional hazards models to assess hospitalizations and deaths in 29,593 patients from the Dialysis Outcomes and Practice Patterns Study with baseline DNa and SNa as predictors, categorized according to lowest to highest levels. RESULTS: IDWG increased with higher DNa across all SNa categories, by 0.17% of body weight per 2 mEq/L higher DNa; however, higher DNa was not associated with higher mortality in a fully adjusted model (also adjusted for SNa; hazard ratio [HR]=0.98 per 2 mEq/L higher DNa, 95% confidence interval [CI] 0.95-1.02). Instead, higher DNa was associated with lower hospitalization risk (HR=0.97 per 2 mEq/L higher DNa, 95% CI 0.95-1.00, P=0.04). Additional adjustments for IDWG did not change these results. In sensitivity analyses restricted to study facilities, in which 90%-100% of patients have the same DNa (56%), the adjusted HR for mortality was 0.88 per 2 mEq/L higher DNa (95% CI 0.83-0.94). These analyses represented a pseudo-randomized experiment in which the association between DNa and mortality is unlikely to have been confounded by indication. CONCLUSIONS: In the absence of randomized prospective studies, the benefit of reducing IDWG by decreasing DNa prescriptions should be carefully weighed against an increased risk for adverse outcomes. PMID- 22052943 TI - Early skeletal and biochemical alterations in pediatric chronic kidney disease. AB - BACKGROUND AND OBJECTIVES: The relationship between parathyroid hormone, fibroblast growth factor 23 (FGF-23), and indices of bone turnover and mineralization in children with early CKD is unknown; thus, this study characterizes the features of renal osteodystrophy and their relationship to biochemical markers of mineral metabolism. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fifty-two patients 2-21 years of age with predialysis CKD underwent tetracycline-labeled bone biopsy. Anthropomorphic measurements and biochemical values were obtained at the time of biopsy. RESULTS: Serum phosphorus levels were increased in 4% of patients with stage 3 CKD and 43% of those with stage 4/5 CKD. Parathyroid hormone concentrations were elevated in 36% of patients with stage 2, 71% with stage 3, and 93% with stage 4/5 CKD, whereas FGF-23 values were elevated in 81% of all patients, regardless of CKD stage. Bone turnover was normal in all patients with stage 2, but was increased in 13% with stage 3 and 29% with stage 4/5 CKD. Defective mineralization was present in 29% of patients with stage 2, 42% with stage 3, and 79% with stage 4/5 CKD. Defective skeletal mineralization was associated with lower serum calcium levels and increased parathyroid hormone concentrations. CONCLUSIONS: Elevated circulating FGF-23 levels and defects in skeletal mineralization early in the course of CKD suggest that factors other than the traditional markers of mineral deficiency play a crucial role in the development of renal bone disease. PMID- 22052945 TI - Exceptionally difficult. PMID- 22052944 TI - Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture. AB - Long QT syndrome (LQTS) is caused by functional alterations in cardiac ion channels and is associated with prolonged cardiac repolarization time and increased risk of ventricular arrhythmias. Inherited type 2 LQTS (LQT2) and drug induced LQTS both result from altered function of the hERG channel. We investigated whether the electrophysiological characteristics of LQT2 can be recapitulated in vitro using induced pluripotent stem cell (iPSC) technology. Spontaneously beating cardiomyocytes were differentiated from two iPSC lines derived from an individual with LQT2 carrying the R176W mutation in the KCNH2 (HERG) gene. The individual had been asymptomatic except for occasional palpitations, but his sister and father had died suddenly at an early age. Electrophysiological properties of LQT2-specific cardiomyocytes were studied using microelectrode array and patch-clamp, and were compared with those of cardiomyocytes derived from control cells. The action potential duration of LQT2 specific cardiomyocytes was significantly longer than that of control cardiomyocytes, and the rapid delayed potassium channel (I(Kr)) density of the LQT2 cardiomyocytes was significantly reduced. Additionally, LQT2-derived cardiac cells were more sensitive than controls to potentially arrhythmogenic drugs, including sotalol, and demonstrated arrhythmogenic electrical activity. Consistent with clinical observations, the LQT2 cardiomyocytes demonstrated a more pronounced inverse correlation between the beating rate and repolarization time compared with control cells. Prolonged action potential is present in LQT2 specific cardiomyocytes derived from a mutation carrier and arrhythmias can be triggered by a commonly used drug. Thus, the iPSC-derived, disease-specific cardiomyocytes could serve as an important platform to study pathophysiological mechanisms and drug sensitivity in LQT2. PMID- 22052946 TI - Systematic review of the benefits of physical therapy within a multidisciplinary care approach for people with schizophrenia. AB - BACKGROUND: Although schizophrenia is the fifth leading cause of disability adjusted life years worldwide in people aged 15 to 44 years, the clinical evidence of physical therapy as a complementary treatment remains largely unknown. PURPOSE: The purpose of this study was to systematically review randomized controlled trials (RCTs) evaluating the effectiveness of physical therapy for people with schizophrenia. DATA SOURCES: EMBASE, PsycINFO, PubMed, ISI Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro), and the Cochrane Library were searched from their inception until July 1, 2011, for relevant RCTs. In addition, manual search strategies were used. STUDY SELECTION: Two reviewers independently determined study eligibility on the basis of inclusion criteria. DATA EXTRACTION: Reviewers rated study quality and extracted information about study methods, design, intervention, and results. DATA SYNTHESIS: Ten RCTs met all selection criteria; 6 of these studies addressed the use of aerobic and strength exercises. In 2 of these studies, yoga techniques also were investigated. Four studies addressed the use of progressive muscle relaxation. There is evidence that aerobic and strength exercises and yoga reduce psychiatric symptoms, state anxiety, and psychological distress and improve health-related quality of life, that aerobic exercise improves short-term memory, and that progressive muscle relaxation reduces state anxiety and psychological distress. LIMITATIONS: The heterogeneity of the interventions and the small sample sizes of the included studies limit overall conclusions and highlight the need for further research. CONCLUSIONS: Physical therapy offers added value in the multidisciplinary care of people with schizophrenia. PMID- 22052947 TI - Lower limb functional index: development and clinimetric properties. AB - BACKGROUND: Existing lower-limb, region-specific, patient-reported outcome measures have clinimetric limitations, including limitations in psychometric characteristics (eg, lack of internal consistency, lack of responsiveness, measurement error) and the lack of reported practical and general characteristics. A new patient-reported outcome measure, the Lower Limb Functional Index (LLFI), was developed to address these limitations. OBJECTIVE: The purpose of this study was to overcome recognized deficiencies in existing lower-limb, region-specific, patient-reported outcome measures through: (1) development of a new lower-extremity outcome scale (ie, the LLFI) and (2) evaluation of the clinimetric properties of the LLFI using the Lower Extremity Functional Scale (LEFS) as a criterion measure. DESIGN: This was a prospective observational study. METHODS: The LLFI was developed in a 3-stage process of: (1) item generation, (2) item reduction with an expert panel, and (3) pilot field testing (n=18) for reliability, responsiveness, and sample size requirements for a larger study. The main study used a convenience sample (n=127) from 10 physical therapy clinics. Participants completed the LLFI and LEFS every 2 weeks for 6 weeks and then every 4 weeks until discharge. Data were used to assess the psychometric, practical, and general characteristics of the LLFI and the LEFS. The characteristics also were evaluated for overall performance using the Measurement of Outcome Measures and Bot clinimetric assessment scales. RESULTS: The LLFI and LEFS demonstrated a single-factor structure, comparable reliability (intraclass correlation coefficient [2,1]=.97), scale width, and high criterion validity (Pearson r=.88, with 95% confidence interval [CI]). Clinimetric performance was higher for the LLFI compared with the LEFS on the Measurement of Outcome Measures scale (96% and 95%, respectively) and the Bot scale (100% and 83%, respectively). The LLFI, compared with the LEFS, had improved responsiveness (standardized response mean=1.75 and 1.64, respectively), minimal detectable change with 90% CI (6.6% and 8.1%, respectively), and internal consistency (alpha=.91 and .95, respectively), as well as readability with reduced user error and completion and scoring times. LIMITATIONS: Limitations of the study were that only participants recruited from outpatient physical therapy clinics were included and that no specific conditions or diagnostic subgroups were investigated. CONCLUSION: The LLFI demonstrated sound clinimetric properties. There was lower response error, efficient completion and scoring, and improved responsiveness and overall performance compared with the LEFS. The LLFI is suitable for assessment of lower-limb function. PMID- 22052948 TI - Delivery of physical therapy in the acute care setting: a population-based study. AB - BACKGROUND: Population-based studies on physical therapy use in acute care are lacking. OBJECTIVES: The purpose of this study was to examine population-based, hospital discharge data from North Carolina to describe the demographic and diagnostic characteristics of individuals who receive physical therapy and, for common diagnostic subgroups, to identify factors associated with the receipt of and intensity of physical therapy use. DESIGN: This was a cross-sectional, descriptive study. METHODS: Hospital discharge data for 2006-2007 from the 128 acute care hospitals in the state were examined to identify the most common diagnoses that receive physical therapy and to describe the characteristics of physical therapy users. For 2 of the most common diagnoses, logistic and linear regression analyses were conducted to identify factors associated with the receipt and intensity of physical therapy. RESULTS: Of the more than 2 million people treated in acute care hospitals, 22.5% received physical therapy (mean age=66 years; 58% female). Individuals with osteoarthritis (admitted for joint replacement) and stroke were 2 of the most common patient types to receive physical therapy. Almost all individuals admitted for a joint replacement received physical therapy, with little between-hospital variation. Between hospital variation in physical therapy use for stroke was greater. Demographic and hospital-related factors were associated with physical therapy use and physical therapy intensity for both diagnoses, after controlling for illness severity and comorbidities. LIMITATIONS: Data from only one state were examined, and the studied variables were limited. CONCLUSIONS: The use and intensity of physical therapy for stroke and joint replacement in acute care hospitals in North Carolina vary by clinical and nonclinical factors. Reasons behind the association of hospital characteristics and physical therapy use need further investigation. PMID- 22052949 TI - In vivo calcium and phosphate iontophoresis for the topical treatment of osteoporosis. AB - BACKGROUND: In addition to systemic treatment, osteoporosis may be treated topically by incorporating calcium and phosphate into the bone. OBJECTIVE: This article describes the use of a recently developed, novel iontophoretic apparatus suitable for local ion delivery into bones. In this study, in vivo experiments were performed to compare the effects of local electrotherapy and those of systemic hormone replacement on bone. DESIGN: In this study, local iontophoresis was carried out in ovariectomized and control rats. Bone density, biomechanical, and elemental studies were performed. METHODS: Forty 12-week-old Sprague-Dawley rats received an ovariectomy (OVX) or were sham-operated (sham). Twenty-one weeks later, tibias of subgroups of sham-operated and OVX animals were subjected to serial local iontophoresis (IOP) treatments, received systemic subcutaneous 17beta-estradiol (E2), or were treated with the combination of IOP and E2. Changes in bone density were detected by quantitative ultrasound densitometry and expressed as amplitude-dependent speed of sound (AD-SoS). Biomechanical studies and elemental analysis were performed at the end of the experiments. RESULTS: Osteopenia developed 21 weeks after OVX in the proximal tibial regions; the mean difference estimate (95% confidence intervals) of AD-SoS values between the sham operated and OVX animals was 188.7 (140.4-237.1). Serial iontophoretic treatment resulted in an increase in bone density in both sham-operated and OVX animals (sham+IOP versus sham: 121.4 [73.01-169.7]; OVX+IOP versus OVX: 241.6 [193.2 289.9]). Similar changes in AD-SoS were detected after 17beta-estradiol (E2) treatment; however, even greater changes occurred after OVX+E2+IOP versus OVX+E2 (123.4 [75.1-171.8]). Similar improvements also were evident regarding the biomechanical features of the tibias. LIMITATIONS: A limitation of this study was the relatively small number of rats. CONCLUSIONS: The efficacy of local IOP using calcium- and phosphate-donating microparticles is comparable to that of estrogen therapy as evidenced by steadily increasing bone density, restoration of the calcium and phosphate balance, and improvement in the biomechanical properties of the bone. PMID- 22052950 TI - Unconventional modified Fontan operation for Ebstein's anomaly. PMID- 22052951 TI - Successful catheter-based occlusion of persistent left-sided superior vena cava draining into the left atrium. PMID- 22052952 TI - A tale of two valves. AB - We present two cases involving elevated gradients across mechanical cardiac valves. Provided images show decreased disc mobility and eventual operative findings. A brief discussion underlines the importance of recognizing pannus as a common aetiology for valve dysfunction. PMID- 22052953 TI - Characteristics and capabilities of emergency departments in Abuja, Nigeria. AB - OBJECTIVES: Emergency departments (ED) are the basic unit of international emergency medicine, but often differ in fundamental features. This study sought to describe and characterise ED in the capital city of Nigeria, Abuja. METHODS: All ED open 24 h/day 7 days/week to the general public were surveyed using the national ED inventories survey instrument (http://www.emnet-nedi.org). ED staff were asked about ED characteristics with reference to calendar year 2008. RESULTS: Twenty-four ED participated (83% response). All were located in hospitals, which ranged in size from six to 250 beds. The majority (92% CI 73% to 100%) had a contiguous layout with medical and surgical care provided in one area. All ED saw both adults and children, with a median of 1500 annual visits (IQR 648-2328). Almost half of respondents (46%; CI 26% to 67%) thought their ED operated under capacity, none thought that their ED was over capacity. Only 4% of ED surveyed had dedicated CT scanners, 25% had cardiac monitoring and none had negative-pressure rooms. There was wide variation in the types of emergencies that were identified as being treatable 24 h/day 7 days/week; these appeared to correlate with ED consultant availability. CONCLUSIONS: Although ED location and layout in Abuja do not differ greatly from that in a typical US city, ED utilisation was lower and fewer resources and capabilities were available. The lack of technological and human resources raise questions about what critical technologies are needed in resource-limited settings, and whether Nigeria should consider training emergency medicine physicians to meet its workforce needs. PMID- 22052954 TI - Hospital emergency management research in China: trends and challenges. AB - Emergency management is a relatively new research field in China. The severe acute respiratory syndrome epidemic in 2003 caused research and papers on emergency management to increase by leaps and bounds. This review summarises the progress of hospital emergency management research in China, highlights trends and challenges, and discusses likely solutions for research improvement. Articles were identified from a systematic search of Wanfang Med Online and PubMed, from reviews of bibliographic reference lists and by consultation with experts in the field. The search identified 2548 articles potentially involving hospital emergency management. By reviewing the titles and abstracts, we narrowed the list to 253. Reading the texts resulted in the inclusion of 85 articles in the review. Two additional articles were included from the references cited in articles that were reviewed. Research progress was summarised in terms of basic concepts and principles, system development, emergency response plan, preparedness and response, training and exercise, and management evaluation. Based on this study we suggest that hospital emergency management research in China should make efforts to (1) establish a universally accepted theory framework and terminology, (2) create a structure for further studies, (3) integrate research of different disciplines, and (4) avoid or minimise confusion. More attention should be paid on the evolvement mechanism of main public health incidents and disasters, and the key functional systems related to hospital's emergency response resiliencies. Focus should also be placed on practical guidelines and tools. PMID- 22052955 TI - Tache noire. PMID- 22052956 TI - Lack of an antagonist to reverse the action of dabigatran. PMID- 22052957 TI - The blues of minocycline. PMID- 22052958 TI - The greens of lead. PMID- 22052959 TI - Enhancement characteristics of lymphomatous lymph nodes of the mediastinum. AB - BACKGROUND: Previous studies of CT enhancement of lymphomatous lymph nodes (LLN) of the neck showed that the LLN had lower enhancement values than normal lymph nodes. PURPOSE: To elucidate the contrast medium enhancement curves of LLN in the mediastinum by comparing the curves of LLN with those of normal lymph nodes, and to compare the present enhancement curves of LLN of the mediastinum with the curves of LLN of the neck from a previous similar investigation. MATERIAL AND METHODS: Twenty-four consecutive patients with LLN in the mediastinum (9 with Hodgkin's lymphoma [HL]) and 23 control patients with sarcomas and thus presumably normal mediastinal nodes underwent dynamic CT examinations. The previous, similar investigation of lymph nodes of the neck comprised 28 patients with LLN and 20 control patients. RESULTS: The enhancement curves of the mediastinal LLN had significantly lower values than those of the mediastinal control nodes. The LLN of the mediastinum had lower mean peak contrast values than the corresponding nodes of the neck from a previous investigation. CONCLUSION: The comparison of enhancement curves of mediastinal LLN with mediastinal control nodes showed a marked similarity with and substantiates our previous findings in lymph nodes of the neck. PMID- 22052960 TI - Phylogenetic relationships of Aristida and relatives (Poaceae, Aristidoideae) based on noncoding chloroplast (trnL-F, rpl16) and nuclear (ITS) DNA sequences. AB - PREMISE: The cosmopolitan and ecologically important grass subfamily Aristidoideae comprises the widely distributed genus Aristida (250-290 species), Stipagrostis (50 species, with an African-Asian distribution), and Sartidia (five species, Africa and Madagascar). The subfamily includes species with C(3) (Sartidia and a single species of Aristida) and C(4) photosynthetic pathways. Rigorous phylogenetic reconstructions of species relationships are required to explain the biogeographic, physiological, and ecological diversity within this subfamily. METHODS: Chloroplast (trnL-F, rpl16) and nuclear (ITS) DNA sequences were obtained from 198 accessions, and the combined data set was subjected to parsimony, maximum likelihood, and Bayesian inference analyses. Dating analyses calibrated using previously published node ages were conducted to determine the ages of major radiations. RESULTS: The C(3) Sartidia is sister to a monophyletic Stipagrostis, and the (Sartidia, Stipagrostis) clade is sister to Aristida. Within Aristida, the only known C(3) species, A. longifolia, is sister to the remainder of the genus. Infrageneric sections of Aristida were not supported, and there are no synapomorphic morphological characters for the clades retrieved. Within Aristida, monophyletic Australian, African, North American, and South American clades are retrieved. CONCLUSIONS: The subfamily dates back to the late Miocene, with the major lineages present by the Pliocene. With one exception, regional clades of Aristida evolved in the Pliocene. The C(3) photosynthetic pathway is hypothesized to be the pleisomorphic condition for the subfamily, wherein two independent C(4) pathways (each with unique anatomical and genetic features) evolved, one within Aristida and one in Stipagrostis. PMID- 22052961 TI - Intricate variation patterns in the diploid-polyploid complex of Alyssum montanum A. repens (Brassicaceae) in the Apennine Peninsula: evidence for long-term persistence and diversification. AB - PREMISE OF THE STUDY: The Apennine Peninsula, one of the three peninsulas of the European Mediterranean, is an important hotspot of genetic and species diversity, but studies devoted to plant evolution are still very scarce in this region. We studied the diploid-polyploid complex of Alyssum montanum-A. repens, focusing on Apennine and adjacent southwestern Alpine populations from southeastern France, with the aim of examining their taxonomic position and evolutionary patterns. METHODS: We employed AFLP markers and cpDNA sequences, along with cytotype determination using flow cytometry, and a multivariate morphometric approach. KEY RESULTS: The Italian and French populations formed two well-delimited groupings within the studied complex that were, in contrast to previous taxonomic treatments, clearly distinct from A. montanum. Populations from southeastern France represent A. orophilum, a previously described but abandoned species. Those from central and southern Italy correspond to A. diffusum, exhibiting high, geographically structured variation (central Apennines, Gargano, and southern Apennines/Calabria). This pattern coincides with hotspot refugial regions, in congruence with the "refugia-within-refugia" hypothesis, and is reflected here in the recognition of three subspecies within A. diffusum. CONCLUSIONS: We provide evidence for the presence of Mediterranean refugia for the studied Alyssum montanum-A. repens complex located in central and southern Italy, which, however, did not contribute to the postglacial colonization of Central Europe. Past extinctions, genetic bottlenecks, and recent expansion were inferred in Central Europe, while long-term accumulation of diversity as well as polyploidization occurred in the Apennines. PMID- 22052962 TI - Microsatellite loci in an endangered fern species, Athyrium viridescentipes (Woodsiaceae), and cross-species amplification. AB - PREMISE OF THE STUDY: Microsatellite markers were characterized in Athyrium viridescentipes, a critically endangered fern species in Japan, to investigate its genetic diversity and population structure. METHODS AND RESULTS: Fifteen microsatellite markers were developed. The 15 loci were successfully amplified in three additional Athyrium species except for one locus in A. vidalii. In A. viridescentipes, the number of alleles per locus ranged from one to five, with an average of 1.9, and the expected heterozygosity ranged from 0.00 to 0.53, with an average of 0.24. CONCLUSIONS: These markers can be used in studies on conservation programs for A. viridescentipes as well as in further studies involving other Athyrium species. PMID- 22052963 TI - A walking intervention for postmenopausal women using mobile phones and Interactive Voice Response. AB - We conducted a feasibility study of a 12-week walking intervention administered through an Interactive Voice Response (IVR) system and mobile phones. We also examined the added benefit of a human coach. Post-menopausal women (n = 71) were given a daily-steps goal, which they monitored using a pedometer. Each day, they answered an automated call from the IVR system to their mobile phone and provided assessments of walking goals and mood. Every evening, they called the IVR system to report their steps, answered a brief questionnaire and received a message with a helpful hint. Participants took less time to complete a one-mile walk after the intervention, compared to baseline (0.77 min, SE = 0.22, P < 0.001). In addition, a significant loss in body weight (0.93 kg, SE = 0.31) and body-mass index (0.28 kg/m(2), SE = 0.11) were observed. The key psychometric measures of exercise goal setting (0.67 units, SE = 0.12) and exercise planning (0.48 units, SE = 0.09) also improved from baseline (both P < 0.001). However, results in the coach and no-coach conditions were not significantly different. The study suggests that mobile phones can be used to deliver an effective, low-cost walking intervention, irrespective of the addition of a human coach. PMID- 22052964 TI - Feasibility of providing nephrology services to remote communities with videoconferencing. AB - We examined the feasibility of telemedicine clinics for patients with chronic kidney disease (not on dialysis) for a period of 18 months. Telemedicine clinics were run at two peripheral hospitals about 100 km from the specialist hospital in Ottawa. A total of 115 questionnaires were completed by patients and providers during the period March 2009 to July 2009. The participants were overwhelmingly positive and wanted telemedicine to continue. Some patients indicated they would discontinue follow-up care if they had to travel to Ottawa. The analysis of staff hours worked showed almost no increase following the introduction of telemedicine. Telemedicine is therefore feasible for follow-up care of remote chronic kidney disease patients. PMID- 22052965 TI - The value of telephone triage for patients with appendicitis. AB - Although it has been assumed that telephone triage can directly benefit patients by facilitating early diagnosis and treatment, this potential benefit has not been well documented. Using appendicitis cases ascertained from claims data, we compared telephone triage recommendations with what the callers originally intended to do. Over a two-year period, there were 20,230 calls to a telephone triage centre in the US where insurance information was available. Of these, 12,709 calls (63%) had insurance claims made within seven days of the call. Among these calls, 46 had a diagnosis of appendicitis. In 72% of calls concerning appendicitis, the telephone triage recommendation was for a more rapid evaluation than the caller originally intended (P < 0.0001). In 91% of the appendicitis cases, triage nurses directed callers to care within 8 h, but without triage advice, only 39% of callers stated they would have sought care within 8 h (P < 0.0001). Telephone triage significantly reduced the delay in care for appendicitis in comparison with what the caller would have done. This suggests that telephone triage potentially reduces the morbidity associated with appendicitis. PMID- 22052966 TI - Home telemental health implementation and outcomes using electronic messaging. AB - In 2007, the VA Connecticut Healthcare System began a home electronic messaging programme for mental health patients. During the first two years, 76 patients with diagnoses of schizophrenia, post traumatic stress disorder, depression and substance-use disorders received a home messaging device, which was connected via an ordinary telephone line. There were daily questions, which were based on disease management protocols, and included alerts, data and educational components. Patient data were sent to a nurse practitioner each day for triage and follow-up. Patients used the device for at least six months. In the six months prior to enrolment, 42 patients were hospitalized for 46 admissions. In the following six months, six patients were hospitalized for nine admissions (P < 0.0001). In the six months prior to enrolment, 47 patients had a total of 80 ER visits. In the following six months, 16 patients had a total of 32 ER visits (P < 0.0001). Questionnaire responses indicated a high level of satisfaction with the home messaging programme. PMID- 22052967 TI - Telecytology in East Africa: a feasibility study of forty cases using a static imaging system. AB - We conducted a pilot study to assess the feasibility of telecytology as a diagnostic tool in difficult cases originating from a hospital in East Africa. Forty cytology cases considered difficult by a referring pathologist were posted on a telepathology website. Six pathologists independently assessed the static images. Telecytology diagnoses were compared with the consensus diagnoses made on glass slides and also with the histogical diagnoses when available. The diagnostic agreement of the six pathologists was 71-93% and tended to be higher for pathologists with more experience. Reasons for discordance included poor image quality, presence of diagnostic cells in thick areas of smears, sampling bias and screening errors. The consensus diagnoses agreed with histological diagnoses in all 17 cases in which a biopsy was performed. Diagnostic accuracy rates (i.e. telecytology diagnosis vs. histological diagnosis) for individual pathologists were 65-88%. To ensure diagnostic accuracy both referring and consulting pathologists must have adequate training in cytology, image acquisition and image-based diagnosis and the diagnostic questions of importance must be clearly communicated by the referring pathologist when posting a case. PMID- 22052968 TI - Language use in social interactions of school-age children with language impairments: an evidence-based systematic review of treatment. AB - INTRODUCTION: Pragmatic models were first applied to the treatment of children with language impairment in the late 1970s. Since that time, the study of language use has had considerable impact on language assessment and treatment. Despite the need to address pragmatic language skills clinically, there has been no systematic examination of the efficacy of treatments developed for this purpose. METHOD: In accordance with the evidence-based practice policy agenda, the American Speech-Language-Hearing Association (ASHA) convened an ad hoc committee on language use in social interactions in school-age children. The committee's charge was to develop an evidence-based systematic review of treatment for disorders of language use in social interactions. This charge was conducted in collaboration with ASHA's National Center for Evidence-Based Practice in Communication Disorders. RESULTS: This systematic review provided preliminary support for the feasibility of various treatment procedures addressing social communication behaviors. Gains were reported in topic management skills, narrative production, and repairs of inadequate or ambiguous comments. CONCLUSION: Because further investigation of these treatments is warranted, the committee is unable to make empirically supported recommendations for changes in standard clinical practice based solely on this review. More research is needed to examine the feasibility of interventions that focus on children's language use. PMID- 22052969 TI - Narrative writing in children and adolescents: examining the literate lexicon. AB - PURPOSE: This study was designed primarily to examine the use of abstract nouns and metacognitive verbs in the narrative writing of school-age children and adolescents. METHOD: Three groups of typically developing students ages 11, 14, and 17 years (n = 40 per group) were asked to write a story about something funny, sad, or scary that had happened to them and a friend. Each student's narrative essay was examined for the use of abstract nouns (e.g., accomplishment, loneliness, mystery) and metacognitive verbs (e.g., assume, discover, realize) and for the production of complex syntax as measured by mean length of T-unit (MLTU) and clausal density (CD). RESULTS: Age-related growth in narrative writing was documented for both types of words. Additionally, the use of abstract nouns and metacognitive verbs was associated with the production of complex syntax, reflecting the lexicon-syntax interface. CONCLUSION: The narrative writing task employed in this study was effective in eliciting literate words and complex syntax in school-age children and adolescents. PMID- 22052970 TI - Dynamic assessment of word learning skills: identifying language impairment in bilingual children. AB - PURPOSE: Bilingual children are often diagnosed with language impairment, although they may simply have fewer opportunities to learn English than English speaking monolingual children. This study examined whether dynamic assessment (DA) of word learning skills is an effective method for identifying bilingual children with primary language impairment (PLI). METHOD: Fifteen 4- and 5-year old predominantly Spanish-speaking children with typical language development (TLD) and 13 with PLI each participated in a 30- to 40-min session of DA of word learning skills following a pretest-teach-posttest design. RESULTS: Results indicated that TLD children made associations between the phonological and semantic representations of the new words faster than children with PLI did, showing greater modifiability. Further, a combination of word learning in the receptive modality and the Learning Strategies Checklist (Lidz, 1991; Pena, 1993) provided the best accuracy in identifying PLI in these children. CONCLUSION: Findings suggest that a brief DA is a promising method for accurately differentiating children with TLD from children with PLI. PMID- 22052971 TI - Preliteracy speech sound production skill and later literacy outcomes: a study using the Templin Archive. AB - PURPOSE: This archival study examined the relationship between the speech sound production skill of kindergarten children and literacy outcomes in Grades 1-3 in a data set where most children's vocabulary skills were within normal limits, speech therapy was not provided until 2nd grade, and phonological awareness instruction was discouraged at the time data were collected. METHOD: Data were accessed from the Templin Archive (2004), and the speech sound production skill of 272 kindergartners were examined relative to literacy outcomes in 1st and 2nd grade (reading) and 3rd grade (spelling). RESULTS: Kindergartners in the 7th percentile for speech sound production skill scored more poorly in 1st- and 2nd grade reading and 3rd-grade spelling than did kindergartners with average speech sound production skill; kindergartners in the 98th percentile achieved superior literacy skills compared to the mean. Phonological awareness mediated the effects of speech sound production skill on reading and spelling; vocabulary did not account for any unique variance. CONCLUSION: Speech sound disorders appear to be an overt manifestation of a complex interaction among variables influencing literacy skills, including nonlanguage cognition, vocabulary, letter knowledge, and phonological awareness. These interrelationships hold across the range of speech sound production skill, as children with superior speech sound production skill experience superior literacy outcomes. PMID- 22052972 TI - Deep human genealogies reveal a selective advantage to be on an expanding wave front. AB - Since their origin, human populations have colonized the whole planet, but the demographic processes governing range expansions are mostly unknown. We analyzed the genealogy of more than one million individuals resulting from a range expansion in Quebec between 1686 and 1960 and reconstructed the spatial dynamics of the expansion. We find that a majority of the present Saguenay Lac-Saint-Jean population can be traced back to ancestors having lived directly on or close to the wave front. Ancestors located on the front contributed significantly more to the current gene pool than those from the range core, likely due to a 20% larger effective fertility of women on the wave front. This fitness component is heritable on the wave front and not in the core, implying that this life-history trait evolves during range expansions. PMID- 22052973 TI - Fermi detection of a luminous gamma-ray pulsar in a globular cluster. AB - We report on the Fermi Large Area Telescope's detection of gamma-ray (>100 mega electron volts) pulsations from pulsar J1823-3021A in the globular cluster NGC 6624 with high significance (~7 sigma). Its gamma-ray luminosity, L(gamma) = (8.4 +/- 1.6) * 10(34) ergs per second, is the highest observed for any millisecond pulsar (MSP) to date, and it accounts for most of the cluster emission. The nondetection of the cluster in the off-pulse phase implies that it contains <32 gamma-ray MSPs, not ~100 as previously estimated. The gamma-ray luminosity indicates that the unusually large rate of change of its period is caused by its intrinsic spin-down. This implies that J1823-3021A has the largest magnetic field and is the youngest MSP ever detected and that such anomalous objects might be forming at rates comparable to those of the more normal MSPs. PMID- 22052974 TI - Crystal structure of the eukaryotic 60S ribosomal subunit in complex with initiation factor 6. AB - Protein synthesis in all organisms is catalyzed by ribosomes. In comparison to their prokaryotic counterparts, eukaryotic ribosomes are considerably larger and are subject to more complex regulation. The large ribosomal subunit (60S) catalyzes peptide bond formation and contains the nascent polypeptide exit tunnel. We present the structure of the 60S ribosomal subunit from Tetrahymena thermophila in complex with eukaryotic initiation factor 6 (eIF6), cocrystallized with the antibiotic cycloheximide (a eukaryotic-specific inhibitor of protein synthesis), at a resolution of 3.5 angstroms. The structure illustrates the complex functional architecture of the eukaryotic 60S subunit, which comprises an intricate network of interactions between eukaryotic-specific ribosomal protein features and RNA expansion segments. It reveals the roles of eukaryotic ribosomal protein elements in the stabilization of the active site and the extent of eukaryotic-specific differences in other functional regions of the subunit. Furthermore, it elucidates the molecular basis of the interaction with eIF6 and provides a structural framework for further studies of ribosome-associated diseases and the role of the 60S subunit in the initiation of protein synthesis. PMID- 22052975 TI - Entorhinal cortex layer III input to the hippocampus is crucial for temporal association memory. AB - Associating temporally discontinuous elements is crucial for the formation of episodic and working memories that depend on the hippocampal-entorhinal network. However, the neural circuits subserving these associations have remained unknown. The layer III inputs of the entorhinal cortex to the hippocampus may contribute to this process. To test this hypothesis, we generated a transgenic mouse in which these inputs are specifically inhibited. The mutant mice displayed significant impairments in spatial working-memory tasks and in the encoding phase of trace fear-conditioning. These results indicate a critical role of the entorhinal cortex layer III inputs to the hippocampus in temporal association memory. PMID- 22052976 TI - Experimental evolution of reduced sex ratio adjustment under local mate competition. AB - Theory predicts that local mate competition (LMC) favors the evolution of female biased sex ratios. Empirical support of this prediction is indirect and comes from comparative studies or from studies showing that individuals can adjust their offspring sex ratio in response to varying LMC intensities. Replicate lines from a population of the spider mite Tetranychus urticae were selected under three LMC intensities for up to 54 generations. Within each selection regime, the final sex ratio matched theoretical predictions. Furthermore, the ability of individuals to adjust their offspring sex ratio diminished in females evolving under strict LMC, but not in females evolving under relaxed LMC levels. These results provide direct experimental evidence for the evolutionary process by which LMC modifies sex-allocation strategies and suggest that evolution under strict and constant LMC may lead to a loss of phenotypic plasticity. PMID- 22052977 TI - Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. AB - Control of intracellular reactive oxygen species (ROS) concentrations is critical for cancer cell survival. We show that, in human lung cancer cells, acute increases in intracellular concentrations of ROS caused inhibition of the glycolytic enzyme pyruvate kinase M2 (PKM2) through oxidation of Cys(358). This inhibition of PKM2 is required to divert glucose flux into the pentose phosphate pathway and thereby generate sufficient reducing potential for detoxification of ROS. Lung cancer cells in which endogenous PKM2 was replaced with the Cys(358) to Ser(358) oxidation-resistant mutant exhibited increased sensitivity to oxidative stress and impaired tumor formation in a xenograft model. Besides promoting metabolic changes required for proliferation, the regulatory properties of PKM2 may confer an additional advantage to cancer cells by allowing them to withstand oxidative stress. PMID- 22052978 TI - Special article: Creation of a guide for the transfer of care of the malignant hyperthermia patient from ambulatory surgery centers to receiving hospital facilities. AB - CLINICAL PROBLEM: Volatile anesthetics and/or succinylcholine may trigger a potentially lethal malignant hyperthermia (MH) event requiring critical care crisis management. If the MH triggering anesthetic is given in an ambulatory surgical center (ASC), then the patient will need to be transferred to a receiving hospital. Before May 2010, there was no clinical guide regarding the development of a specific transfer plan for MH patients in an ASC. MECHANISM BY WHICH THE STATEMENT WAS GENERATED: A consensual process lasting 18 months among 13 representatives of the Malignant Hyperthermia Association of the United States, the Ambulatory Surgery Foundation, the Society for Ambulatory Anesthesia, the Society for Academic Emergency Medicine, and the National Association of Emergency Medical Technicians led to the creation of this guide. EVIDENCE FOR THE STATEMENT: Most of the guide is based on the clinical experience and scientific expertise of the 13 representatives. The list of representatives appears in Appendix 1. The recommendation that IV dantrolene should be initiated pending transfer is also supported by clinical research demonstrating that the likelihood of significant MH complications doubles for every 30-minute delay in dantrolene administration (Anesth Analg 2010;110:498-507). STATEMENT: This guide includes a list of potential clinical problems and therapeutic interventions to assist each ASC in the development of its own unique MH transfer plan. Points to consider include receiving health care facility capabilities, indicators of patient stability and necessary report data, transport team considerations and capabilities, implementation of transfer decisions, and coordination of communication among the ASC, the receiving hospital, and the transport team. See Appendix 2 for the guide. PMID- 22052979 TI - Pharmacological studies of methoxycarbonyl etomidate's carboxylic acid metabolite. AB - BACKGROUND: Methoxycarbonyl etomidate (MOC-etomidate) is a rapidly metabolized and ultrashort-acting etomidate analog that does not produce prolonged adrenocortical suppression after bolus administration. Its metabolite (MOC-ECA) is a carboxylic acid whose pharmacology is undefined. We hypothesized that MOC ECA possesses significantly lower pharmacological activity than MOC-etomidate, accounting for the latter's very brief duration of hypnotic action and inability to produce prolonged adrenocortical suppression after bolus administration. To test this hypothesis, we compared the potencies of MOC-ECA and MOC-etomidate in 3 biological assays. METHODS: The hypnotic potency of MOC-ECA was assessed in tadpoles using a loss-of-righting reflexes assay. The gamma-aminobutyric acid type A (GABA(A)) receptor modulatory potencies of MOC-ECA and MOC-etomidate were compared by defining the concentrations of each required to directly activate alpha(1)(L264T)beta(2)gamma(2L) GABA(A) receptors. The adrenocortical inhibitory potencies of MOC-ECA and MOC-etomidate were compared by defining the concentrations of each required to inhibit in vitro cortisol production by adrenocortical cells. RESULTS: MOC-ECA's 50% effective concentration for loss-of righting reflexes in tadpoles was 2.8 +/- 0.64 mM as compared with a previously reported value of 8 +/- 2 MUM for MOC-etomidate. The 50% effective concentrations for direct activation of GABA(A) receptors were 3.5 +/- 0.63 mM for MOC-ECA versus 10 +/- 2.5 MUM for MOC-etomidate. The half-maximal inhibitory concentration for inhibiting in vitro cortisol production by adrenocortical cells was 30 +/- 7 MUM for MOC-ECA versus 0.10 +/- 0.02 MUM for MOC-etomidate. CONCLUSIONS: In all 3 biological assays, MOC-ECA's potency was approximately 300 fold lower than that of MOC-etomidate. PMID- 22052980 TI - Management of a symptomatic patient with a high transvalvular gradient across a stentless aortic valve. PMID- 22052981 TI - Isoflurane anesthesia preserves liver and lung mitochondrial oxidative capacity after gut ischemia-reperfusion. AB - BACKGROUND: Lung and liver dysfunction is involved in gut ischemia-reperfusion (IR)-induced multiple organ failure. We compared the effects of ketamine and isoflurane on liver and lung mitochondrial oxidative capacity after gut IR. METHODS: Adult male Wistar rats were randomized into 4 groups (controls and gut IR receiving either intraperitoneal ketamine or inhaled isoflurane). Maximal oxygen consumption and the activity of respiratory chain complexes were measured on isolated liver and lung mitochondria. RESULTS: Gut IR significantly impaired liver and lung mitochondrial oxidative capacity when using ketamine but not isoflurane. CONCLUSIONS: Isoflurane preserved liver and lung mitochondrial oxidative capacity after gut IR. PMID- 22052982 TI - The epidemiology of upper airway injury in patients undergoing major surgical procedures. AB - BACKGROUND: Airway injury is a potentially serious and costly adverse event of anesthesia care. The epidemiologic characteristics of airway injury have not been well documented. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) is a multicenter, prospective, outcome oriented database for patients undergoing major surgical procedures. Using the NSQIP data for the years 2005 to 2008, we examined the incidence of, and risk factors for, airway injury. RESULTS: Of the 563,190 patients studied, 1202 (0.2%) sustained airway injury. The most common airway injury was lip laceration/hematoma (61.4%), followed by tooth injury (26.1%), tongue laceration (5.7%), pharyngeal laceration (4.7%), and laryngeal laceration (2.1%). Multivariable logistic modeling revealed an increased risk of airway injury in patients with Mallampati class III (adjusted odds ratio [OR], 1.69; 99% confidence interval [CI], 1.36-2.11, relative to patients with Mallampati classes I and II) or class IV (adjusted OR, 2.6; 99% CI, 1.52-4.02), and in patients aged 80 years or older (adjusted OR, 1.50; 99% CI, 1.02-2.19, relative to patients aged 40 to 49 years). CONCLUSIONS: The risk of airway injury for patients undergoing major surgical procedures is approximately 1 in 500. Patients with difficult airways as indicated by Mallampati classes III and IV are at significantly increased risk of sustaining airway injury during anesthesia for major surgical procedures. PMID- 22052983 TI - Focal cerebral ischemia after surgery in the "beach chair" position: the role of a congenital variation of circle of Willis anatomy. AB - A 50-year-old man underwent shoulder surgery in the beach chair position. His mean arterial blood pressure at arm level was approximately 65 mm Hg. Postoperatively, there was delayed awakening and a right hemiparesis. Radiologic evaluation revealed a congenital asymmetry of the circle of Willis that resulted in limited collateral flow to the left anterior and middle cerebral artery distributions. Similar anatomical variations are relatively common in the general population and may render some patients relatively and unpredictably more vulnerable to hypotension. PMID- 22052984 TI - Functional characterization of gynodioecy in Fragaria vesca ssp. bracteata (Rosaceae). AB - BACKGROUND AND AIMS: Gynodioecy is a phylogenetically widespread and important sexual system where females coexist with hermaphrodites. Because dioecy can arise from gynodioecy, characterization of gynodioecy in close relatives of dioecious and sub-dioecious species can provide insight into this transition. Thus, we sought to determine whether Fragaria vesca ssp. bracteata, a close relative to F. chiloensis and F. virginiana, exhibits the functional and population genetic hallmarks of a gynodioecious species. METHODS: We compared reproductive allocation of females and hermaphrodites grown in the greenhouse and estimated genetic diversity (allelic diversity, heterozygosity) and inbreeding coefficients for field-collected adults of both sexes using simple sequence repeat (SSR) markers. We estimated mating system and early seed fitness from open-pollinated families of both sex morphs. KEY RESULTS: Under greenhouse conditions, females and hermaphrodites allocated similarly to all reproductive traits except flower number, and, as a consequence, females produced 30 % fewer seeds per plant than hermaphrodites. Under natural conditions, hermaphrodites produce seeds by self fertilization approx. 75 % of the time, and females produced outcrossed seeds with very little biparental inbreeding. Consistent with inbreeding depression, seeds from open-pollinated hermaphrodites were less likely to germinate than those from females, and family-level estimates of hermaphrodite selfing rates were negatively correlated with germination success and speed. Furthermore, estimates of inbreeding depression based on genetic markers and population genetic theory indicate that inbreeding depression in the field could be high. CONCLUSIONS: The joint consideration of allocation and mating system suggests that compensation may be sufficient to maintain females given the current understanding of sex determination. Fragaria vesca ssp. bracteata exhibited similar sex morph-dependent patterns of mating system and genetic diversity, but less reproductive trait dimorphism, than its sub-dioecious and dioecious congeners. PMID- 22052985 TI - Glutathione S-transferase P1 c.313A > G polymorphism could be useful in the prediction of doxorubicin response in breast cancer patients. AB - BACKGROUND: Identification of predicting factors for anthracyclines-based chemotherapy remains a clinical challenge. Glutathione S-transferase (GSTs) enzymes detoxify chemotherapy drugs and their metabolites. Several polymorphisms in GST genes result in reduced or no activity of the enzymes. Specifically, GSTM1 and GSTT1 genes are polymorphically deleted, the polymorphism GSTP1 c.313A>G (rs1695) determines the amino acid substitution Ile105Val, where the Val containing enzyme has reduced activity. Also, GSTA1*B allele has reduced levels of GSTA1 enzyme. Several polymorphisms in GSTs have been associated with differences in survival for cancer patients treated with chemotherapy. PATIENTS AND METHODS: We genotyped a total of five polymorphisms in GSTM1, GSTT1, GSTP1 and GSTA1 genes in 159 patients with locally advanced breast cancer, treated with single-agent doxorubicin or docetaxel (Taxotere). Gene expression microarrays were performed in 67 breast tumor samples. We correlate this data with treatment outcome. RESULTS: In multivariate analysis, patients homozygous GG for GSTP1 c.313A>G SNP had a lower risk of chemoresistance when treated with doxorubicin (odds ratio 0.106; confidence interval 0.012-0.898; P=0.040). No association was found in the docetaxel arm. Also, we found that GSTP1 expression varied significantly among breast cancer molecular subtypes. CONCLUSIONS: GSTP1 may constitute another tool contributing to individualized anthracycline-based therapy. PMID- 22052986 TI - Proanthocyanidins and other flavonoids in relation to pancreatic cancer: a case control study in Italy. AB - BACKGROUND: Four cohort studies have examined the relation between flavonoids and pancreatic cancer risk providing inconsistent results. PATIENTS AND METHODS: We conducted a case-control study between 1991 and 2008 in Northern Italy. Subjects were 326 cases with incident pancreatic cancer and 652 frequency-matched controls (admitted to the same hospitals as cases for acute non-neoplastic conditions) who answered a reproducible and valid food-frequency questionnaire. We computed odds ratios (ORs) using logistic regression models conditioned on gender, age and study center, and adjusted for education, history of diabetes, tobacco smoking, alcohol drinking and energy intake. RESULTS: Proanthocyanidins with three or more mers were inversely related to pancreatic cancer risk. The ORs were similar in all classes of polymers with three or more mers and in their combination (OR for the highest versus the lowest quintile of intake, 0.41; 95% confidence interval 0.24-0.69), and did not substantially change after adjustment for fruit and vegetable consumption, and for vitamin C and folate intakes. Eating an additional portion of fruits rich in proanthocyanidins every day reduced the risk of pancreatic cancer by 25%. CONCLUSION: Dietary proanthocyanidins-mostly present in apples, pears and pulses-may convey some protection against pancreatic cancer risk. PMID- 22052987 TI - Large body size and sedentary lifestyle during childhood and early adulthood and esophageal squamous cell carcinoma in a high-risk population. AB - BACKGROUND: Little is known about the association of obesity and physical activity at young ages with subsequent risk of esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Between 2003 and 2007, we conducted a case-control study in a high-risk population in northeastern Iran. Three hundred ESCC cases and 571 matched controls were recruited. Each individual was shown a standard pictogram, to report body size at ages 15 and 30. Demographic and health-related information, including physical activity at these ages was also collected. RESULTS: In the fully adjusted models, very obese body size (last two pictograms) at age 15 [odds ratio (OR) 3.2, 95% confidence interval (CI) 1.3-7.7] and age 30 (OR 3.1; 95% CI 1.1-8.5) were associated with ESCC in women, but not in men. Sedentary work at age 15 (OR 3.3, 95% CI 1.3-8.3) and 30 (OR 18.2, 95% CI 3.9 86.2) were also associated with ESCC risk in women only. The increased risk in women at age 15 remained high after later reduction in body size, while women who became very obese only at age 30 did not show a significantly increased risk. CONCLUSION: These results highlight the importance of early lifestyle modifications in the context of cancer prevention, particularly in women. PMID- 22052988 TI - Incidence, risk factors and clinical implications of venous thromboembolism in cancer patients treated within the context of phase I studies: the 'SENDO experience'. AB - BACKGROUND: To investigate the incidence, risk factors and clinical implications of venous thromboembolism (VTE) in advanced cancer patients treated in phase I studies. PATIENTS AND METHODS: Patients enrolled and treated in phase I studies conducted by SENDO (Southern Europe New Drugs Organization) Foundation between 2000 and 2010 in 15 experimental centers were considered for the study. Clinical data, including adverse events, were prospectively collected during the studies and retrospectively pooled for VTE analysis. RESULTS: Data of 1415 patients were considered for analysis. Five hundred and twenty-six (37.2%) patients were males, and median age was 57.3 years (range: 13-85). Eighty-five percent of patients had metastatic disease, while the remaining had locally advanced irresectable disease. For 706 (49.9%) of the patients, the study treatment was with cytotoxic agent(s) only, for 314 with target therapy(ies) only, while the remaining patients received a target therapy in combination with a cytotoxic drug. Fifty six (3.96%) patients who developed a VTE, almost all (89.3%) during the course of treatment, the remaining during the follow-up. At univariate analysis, the Khorana score, the combination of an antiangiogenic agent with a cytotoxic drug, and the time from first cancer diagnosis to study entry (as continuous variable) were associated with a statistically significant increase of VTE occurrence. The multivariate analysis confirmed only a statistically significant association for the Khorana score. The hazard ratio of VTE occurrence was 7.88 [95% confidence interval (CI) 2.86-21.70) and 2.74 (95% CI 1.27-5.92) times higher for the highest (>=3) and intermediate (1-2) scores as compared with score = 0. CONCLUSIONS: VTE is a relatively common complication among patients treated in the context of phase I studies. The Khorana score predicts VTE development and can be used to identify patients at high of VTE. PMID- 22052989 TI - Better value cancer care for the 21st century. PMID- 22052992 TI - Direct maximization of protein identifications from tandem mass spectra. AB - The goal of many shotgun proteomics experiments is to determine the protein complement of a complex biological mixture. For many mixtures, most methodological approaches fall significantly short of this goal. Existing solutions to this problem typically subdivide the task into two stages: first identifying a collection of peptides with a low false discovery rate and then inferring from the peptides a corresponding set of proteins. In contrast, we formulate the protein identification problem as a single optimization problem, which we solve using machine learning methods. This approach is motivated by the observation that the peptide and protein level tasks are cooperative, and the solution to each can be improved by using information about the solution to the other. The resulting algorithm directly controls the relevant error rate, can incorporate a wide variety of evidence and, for complex samples, provides 18-34% more protein identifications than the current state of the art approaches. PMID- 22052993 TI - Recommendations for mass spectrometry data quality metrics for open access data (corollary to the Amsterdam Principles). AB - Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data quality metrics. On September 18, 2010, the United States National Cancer Institute convened the "International Workshop on Proteomic Data Quality Metrics" in Sydney, Australia, to identify and address issues facing the development and use of such methods for open access proteomics data. The stakeholders at the workshop enumerated the key principles underlying a framework for data quality assessment in mass spectrometry data that will meet the needs of the research community, journals, funding agencies, and data repositories. Attendees discussed and agreed up on two primary needs for the wide use of quality metrics: 1) an evolving list of comprehensive quality metrics and 2) standards accompanied by software analytics. Attendees stressed the importance of increased education and training programs to promote reliable protocols in proteomics. This workshop report explores the historic precedents, key discussions, and necessary next steps to enhance the quality of open access data. By agreement, this article is published simultaneously in the Journal of Proteome Research, Molecular and Cellular Proteomics, Proteomics, and Proteomics Clinical Applications as a public service to the research community. The peer review process was a coordinated effort conducted by a panel of referees selected by the journals. PMID- 22052994 TI - Development of a research ethics knowledge and analytical skills assessment tool. AB - INTRODUCTION: The goal of this project was to develop and validate a new tool to evaluate learners' knowledge and skills related to research ethics. METHODS: A core set of 50 questions from existing computer-based online teaching modules were identified, refined and supplemented to create a set of 74 multiple-choice, true/false and short answer questions. The questions were pilot-tested and item discrimination was calculated for each question. Poorly performing items were eliminated or refined. Two comparable assessment tools were created. These assessment tools were administered as a pre-test and post-test to a cohort of 58 Indian junior health research investigators before and after exposure to a new course on research ethics. Half of the investigators were exposed to the course online, the other half in person. Item discrimination was calculated for each question and Cronbach's alpha for each assessment tool. A final version of the assessment tool that incorporated the best questions from the pre-/post-test phase was used to assess retention of research ethics knowledge and skills 3 months after course delivery. RESULTS: The final version of the REKASA includes 41 items and had a Cronbach's alpha of 0.837. CONCLUSION: The results illustrate, in one sample of learners, the successful, systematic development and use of a knowledge and skills assessment tool in research ethics capable of not only measuring basic knowledge in research ethics and oversight but also assessing learners' ability to apply ethics knowledge to the analytical task of reasoning through research ethics cases, without reliance on essay or discussion-based examination. These promising preliminary findings should be confirmed with additional groups of learners. PMID- 22052995 TI - Circulation of multiple enterovirus serotypes causing hand, foot and mouth disease in India. AB - Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, can be caused by enteroviruses. Coxsackievirus A16 (CV-A16) and enterovirus 71(EV-71) are the major aetiological agents of HFMD. Other EV serotypes, CV-A4-7, CV-A9-10, CV-B1-3, CV-B5, E-4 and E-19, have also been found associated with both sporadic infections and outbreaks of HFMD. In India, outbreaks of HFMD have been documented; however, molecular characterization of the aetiological agents has rarely been reported. Cases of HFMD were identified during 2009-2010 on the basis of clinical features in southern and eastern parts of India. The aim of the present study was to detect and characterize the aetiological agents associated with the disease. A total of 89 specimens consisting of 41 sera, 24 vesicular fluids, 18 stools and 6 throat swabs were collected from 61 clinically diagnosed HFMD cases from southern and eastern parts of India. RT-PCR followed by sequencing of PCR amplicons and phylogenetic analysis were performed on all specimens for detection of EV RNA and identification of EV types. EV RNA was detected in 47.1 % (42/89) of the specimens collected from 57.4 % (35/61) of the HFMD cases. Thirty-six of 42 EV strains showed amplification of the VP1/2A junction or VP1 regions. Sequence analysis of the amplicons identified the presence of CV-A16 (54.8 %), CV-A6 (38.1 %), EV-71 (2.4 %), CV-A10 (2.4 %) and E-9 (2.4 %) serotypes in the HFMD cases. The study documents CV-A16 and CV-A6 as major and CV-A10, EV-71 and E-9 as rare viral pathogens of HFMD in India. PMID- 22052996 TI - Inhibitory effects of native and recombinant full-length camel lactoferrin and its N and C lobes on hepatitis C virus infection of Huh7.5 cells. AB - Lactoferrin has been suggested to have antiviral activity against hepatitis C virus (HCV). The objective of this study was to compare the effects of recombinant camel lactoferrin (rcLf), native camel lactoferrin (ncLf) and their N and C fragments on HCV infection in Huh7.5 cells. ncLf was purified from camel milk and N and C lobes were generated proteolytically. rcLf and its fragments were synthesized using a Bac-to-Bac baculovirus expression system. All proteins except the C lobe of rcLf were soluble. The inhibitory effects on HCV entry into Huh7.5 cells were evaluated by incubation of HCV with Lf prior to infection or pre-treatment of the cells with Lf prior to infection. The inhibitory effect on HCV amplification in Huh7.5 cells was determined by Lf treatment of HCV-infected cells. Nested RT-PCR was performed to amplify intracellular HCV 5' non-coding RNA sequences. rcLf and ncLf and their fragments could prevent HCV entry into Huh7.5 cells by direct interaction with the virus and inhibited virus amplification in Huh7.5 cells. Therefore, the N and C lobes of ncLf are sufficient to elicit anti HCV effects in Huh7.5 cells. rcLf and its N lobe displayed similar HCV inhibitory effects to their native counterparts and may constitute an efficient and cost effective approach for potential clinical applications. PMID- 22052997 TI - Circadian metabolic regulation through crosstalk between casein kinase 1delta and transcriptional coactivator PGC-1alpha. AB - Circadian clock coordinates behavior and physiology in mammals in response to light and feeding cycles. Disruption of normal clock function is associated with increased risk for cardiovascular and metabolic diseases, underscoring the emerging concept that temporal regulation of tissue metabolism is a fundamental aspect of energy homeostasis. We have previously demonstrated that transcriptional coactivator, peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), coordinates circadian metabolic rhythms through simultaneous regulation of metabolic and clock gene expression. In this study, we found that PGC-1alpha physically interacts with, and is phosphorylated by, casein kinase 1delta (CK1delta), a core component of the circadian pacemaker. CK1delta represses the transcriptional function of PGC-1alpha in cultured hepatocytes, resulting in decreased gluconeogenic gene expression and glucose secretion. At the molecular level, CK1delta phosphorylation of PGC-1alpha within its arginine/serine-rich domain enhances its degradation through the proteasome system. Together, these results elucidate a novel mechanism through which circadian pacemaker transduces timing signals to the metabolic regulatory network that controls hepatic energy metabolism. PMID- 22052998 TI - In vitro and in vivo molecular imaging of estrogen receptor alpha and beta homo- and heterodimerization: exploration of new modes of receptor regulation. AB - Estrogen receptor (ER) biology reflects the actions of estrogens through the two receptors, ERalpha and ERbeta, although little is known regarding the preference for formation of ER homo- vs. heterodimers, and how this is affected by the level of ligand occupancy and preferential ligand affinity for one of the ER subtypes. In this report, we use a split optical reporter-protein complementation system to demonstrate the physical interaction between ERalpha and ERbeta in response to different ER ligands in cells and, for the first time, by in vivo imaging in living animals. The genetically encoded reporter vectors constructed with the ligand-binding domains of ERalpha and ERbeta, fused to split firefly or Renilla luciferase (Fluc or hRluc) fragments, were used for this study. This molecular proteomic technique was used to detect ERalpha/ERalpha or ERbeta/ERbeta homodimerization, or ERalpha/ERbeta heterodimerization induced by ER subtype selective and nonselective ligands, and selective ER modulators (SERM), as well as in dimers in which one mutant monomer was unable to bind estradiol. The SERM bound ERalpha and ERbeta form the strongest dimers, and subtype-preferential homodimerization was seen with ERalpha-selective ligands (methyl piperidino pyrazole/propyl pyrazole triol) and the ERbeta-selective ligands (diarylpropionitrile/tetrahydrochrysene/genistein). We also demonstrated that a single ligand-bound monomer can form homo- or heterodimers with an apo-monomer. Xenografts of human embryonic kidney 293T cells imaged in living mice by bioluminescence showed real-time ligand induction of ERalpha/ERbeta heterodimerization and reversal of dimerization upon ligand withdrawal. The results from this study demonstrate the value of the split luciferase-based complementation system for studying ER-subtype interactions in cells and for evaluating them in living animals by noninvasive imaging. They also probe what combinations of ERalpha and ERbeta dimers might be the mediators of the effects of different types of ER ligands given at different doses. PMID- 22052999 TI - Silencing of GSTP1, a prostate cancer prognostic gene, by the estrogen receptor beta and endothelial nitric oxide synthase complex. AB - We recently identified in prostate tumors (PCa) a transcriptional prognostic signature comprising a significant number of genes differentially regulated in patients with worse clinical outcome. Induction of up-regulated genes was due to chromatin remodeling by a combinatorial complex between estrogen receptor (ER) beta and endothelial nitric oxide synthase (eNOS). Here we show that this complex can also repress transcription of prognostic genes that are down-regulated in PCa, such as the glutathione transferase gene GSTP1. Silencing of GSTP1 is a common early event in prostate carcinogenesis, frequently caused by promoter hypermethylation. We validated loss of glutathione transferase (GST) P1-1 expression in vivo, in tissue microarrays from a retrospective cohort of patients, and correlated it with decreased disease-specific survival. Furthermore, we show that in PCa cultured cells ERbeta/eNOS causes GSTP1 repression by being recruited at estrogen responsive elements in the gene promoter with consequential remodeling of local chromatin. Treatment with ERbeta antagonist or its natural ligand 5alpha-androstane-3beta,17beta-diol, eNOS inhibitors or ERbeta small interference RNA abrogated the binding and reversed GSTP1 silencing, demonstrating the direct involvement of the complex. In vitro, GSTP1 silencing by ERbeta/eNOS was specific for cells from patients with worse clinical outcome where it appeared the sole mechanism regulating GSTP1 expression because no promoter hypermethylation was present. However, in vivo chromatin immunoprecipitation assays on fresh PCa tissues demonstrated that silencing by ERbeta/eNOS can coexist with promoter hypermethylation. Our findings reveal that the ERbeta/eNOS complex can exert transcriptional repression and suggest that this may represent an epigenetic event favoring inactivation of the GSTP1 locus by methylation. Moreover, abrogation of ERbeta/eNOS function by 3beta-adiol emphasizes the significance of circulating or locally produced sex steroid hormones or their metabolites in PCa biology with relevant clinical/therapeutic implications. PMID- 22053000 TI - Endoplasmic reticulum stress decreases intracellular thyroid hormone activation via an eIF2a-mediated decrease in type 2 deiodinase synthesis. AB - Cells respond rapidly to endoplasmic reticulum (ER) stress by blocking protein translation, increasing protein folding capacity, and accelerating degradation of unfolded proteins via ubiquitination and ER-associated degradation pathways. The ER resident type 2 deiodinase (D2) is normally ubiquitinated and degraded in the proteasome, a pathway that is accelerated by enzyme catalysis of T(4) to T(3). To test whether D2 is normally processed through ER-associated degradation, ER stress was induced in cells that endogenously express D2 by exposure to thapsigargin or tunicamycin. In all cell models, D2 activity was rapidly lost, to as low as of 30% of control activity, without affecting D2 mRNA levels; loss of about 40% of D2 activity and protein was also seen in human embryonic kidney 293 cells transiently expressing D2. In primary human airway cells with ER stress resulting from cystic fibrosis, D2 activity was absent. The rapid ER stress induced loss of D2 resulted in decreased intracellular D2-mediated T(3) production. ER stress-induced loss of D2 was prevented in the absence of T(4), by blocking the proteasome with MG-132 or by treatment with chemical chaperones. Notably, ER stress did not alter D2 activity half-life but rather decreased D2 synthesis as assessed by induction of D2 mRNA and by [(35)S]methionine labeling. Remarkably, ER-stress-induced loss in D2 activity is prevented in cells transiently expressing an inactive eukaryotic initiation factor 2, indicating that this pathway mediates the loss of D2 activity. In conclusion, D2 is selectively lost during ER stress due to an eukaryotic initiation factor 2 mediated decrease in D2 synthesis and sustained proteasomal degradation. This explains the lack of D2 activity in primary human airway cells with ER stress resulting from cystic fibrosis. PMID- 22053002 TI - Poly(ADP-ribose)polymerase-1 (PARP1) controls adipogenic gene expression and adipocyte function. AB - Poly(ADP-ribose)polymerase-1 (PARP1) is a chromatin-associated enzyme that was described to affect chromatin compaction. Previous reports suggested a dynamic modulation of the chromatin landscape during adipocyte differentiation. We thus hypothesized that PARP1 plays an important transcriptional role in adipogenesis and metabolism and therefore used adipocyte development and function as a model to elucidate the molecular action of PARP1 in obesity-related diseases. Our results show that PARP1-dependent ADP-ribose polymer (PAR) formation increases during adipocyte development and, at late time points of adipogenesis, is involved in the sustained expression of PPARgamma2 and of PPARgamma2 target genes. During adipogenesis, PARP1 was recruited to PPARgamma2 target genes such as CD36 or aP2 in a PAR-dependent manner. Our results also reveal a PAR-dependent decrease in repressory histone marks (e.g. H3K9me3) and an increase in stimulatory marks (e.g. H3K4me3) at the PPARgamma2 promoter, suggesting that PARP1 may exert its regulatory function during adipogenesis by altering histone marks. Interestingly, activation of PARP1 enzymatic activity was prevented with a topoisomerase II inhibitor. These data hint at topoisomerase II-dependent, transient, site-specific double-strand DNA breaks as the cause for poly(ADP) ribose formation, adipogenic gene expression, and adipocyte function. Together, our study identifies PARP1 as a critical regulator of PPARgamma2-dependent gene expression with implications in adipocyte function and obesity-related disease models. PMID- 22053003 TI - Diazocyte development in the marine diazotrophic cyanobacterium Trichodesmium. AB - The establishment of non-diazotrophic cultures of the filamentous marine cyanobacterium Trichodesmium erythraeum IMS101 enabled the first detailed investigation of the process leading to the development of its unique nitrogen fixing cell type, the diazocyte. Trichome heterogeneity was apparent already within 3-8 h, while the differentiation of mature diazocytes, containing the nitrogenase enzyme, required 27 h after the removal of combined nitrogen. The distribution of 'pro-diazocytes' within the trichomes correlates with the localization of mature diazocytes, which suggests that pattern regulation is an early event during diazocyte development. The development was initially identified as changes in the subcellular ultrastructure, most notably the degradation of glycogen granules and gas vacuoles. These changes were preceded by the induced expression of the global nitrogen regulator ntcA at an early stage of combined nitrogen deprivation, followed by elevated expression of genes related to nitrogen metabolism and their corresponding proteins. The strongest induction (10-fold) was related to the transcription of the respiratory gene coxB2, apparent already at an early stage, which suggests an important role for respiration and the subsequent energy generation in the subcellular changes found, and in the creation of the reducing environment required for nitrogen fixation in diazocytes. PMID- 22053001 TI - Small molecule inhibition of the steroid receptor coactivators, SRC-3 and SRC-1. AB - Overexpression of steroid receptor coactivator (SRC)-1 and SRC-3 is associated with cancer initiation, metastasis, advanced disease, and resistance to chemotherapy. In most of these cases, SRC-1 and SRC-3 have been shown to promote tumor cell growth by activating nuclear receptor and multiple growth factor signaling cascades that lead to uncontrolled tumor cell growth. Up until now, most targeted chemotherapeutic drugs have been designed largely to block a single pathway at a time, but cancers frequently acquire resistance by switching to alternative growth factor pathways. We reason that the development of chemotherapeutic agents against SRC coactivators that sit at the nexus of multiple cell growth signaling networks and transcriptional factors should be particularly effective therapeutics. To substantiate this hypothesis, we report the discovery of 2,2'-bis-(Formyl-1,6,7-trihydroxy-5-isopropyl-3 methylnaphthalene (gossypol) as a small molecule inhibitor of coactivator SRC-1 and SRC-3. Our data indicate that gossypol binds directly to SRC-3 in its receptor interacting domain. In MCF-7 breast cancer cells, gossypol selectively reduces the cellular protein concentrations of SRC-1 and SRC-3 without generally altering overall protein expression patterns, SRC-2, or other coactivators, such as p300 and coactivator-associated arginine methyltransferase 1. Gossypol reduces the concentration of SRC-3 in prostate, lung, and liver cancer cell lines. Gossypol inhibits cell viability in the same cancer cell lines where it promotes SRC-3 down-regulation. Additionally, gossypol sensitizes lung and breast cancer cell lines to the inhibitory effects of other chemotherapeutic agents. Importantly, gossypol is selectively cytotoxic to cancer cells, whereas normal cell viability is not affected. This data establish the proof-of-principle that, as a class, SRC-1 and SRC-3 coactivators are accessible chemotherapeutic targets. Given their function as integrators of multiple cell growth signaling systems, SRC-1/SRC-3 small molecule inhibitors comprise a new class of drugs that have potential as novel chemotherapeutics able to defeat aspects of acquired cancer cell resistance mechanisms. PMID- 22053004 TI - Serum albumin alters the expression of iron-controlled genes in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa, which causes serious infections in immunocompromised patients, produces numerous virulence factors, including exotoxin A and the siderophore pyoverdine. As production of these virulence factors is influenced by the host environment, we examined the effect serum has on global transcription within P. aeruginosa strain PAO1 at different phases of growth in an iron deficient medium. At early exponential phase, serum significantly enhanced expression of 138 genes, most of which are repressed by iron, including pvdS, regA and the pyoverdine synthesis genes. However, serum did not interfere with the repression of these genes by iron. Serum enhanced regA expression in a fur mutant of PAO1 but not in a pvdS mutant. The serum iron-binding protein apotransferrin, but not ferritin, enhanced regA and pvdS expression. However, in PAO1 grown in a chemically defined medium that contains no iron, serum but not apotransferrin enhanced pvdS and regA expression. While complement inactivation failed to eliminate this effect, albumin absorption reduced the effect of serum on pvdS and regA expression in the iron-deficient medium chelexed tryptic soy broth dialysate. Additionally, albumin absorption eliminated the effect of serum on pvdS and regA expression in the chemically defined medium. These results suggest that serum enhances the expression of P. aeruginosa iron-controlled genes by two mechanisms: one through apotransferrin and another one through albumin. PMID- 22053005 TI - Construction of Bifidobacterium infantis as a live oral vaccine that expresses antigens of the major fimbrial subunit (CfaB) and the B subunit of heat-labile enterotoxin (LTB) from enterotoxigenic Escherichia coli. AB - We sought to develop Bifidobacterium infantis (BI) as a vehicle for the expression of heterologous antigens. Two proteins of enterotoxigenic Escherichia coli (ETEC) were expressed in BI: CfaB, a major fimbrial subunit protein, and LTB, the B subunit of heat-labile enterotoxin. The expression of CfaB and LTB in BI was verified by electrophoretic analysis. Sprague-Dawley rats were then subjected to intragastric immunization with BI-CfaB and BI-LTB systems both separately and together. ELISA was used to characterize the serum and mucosal immune responses against ETEC antigens. The immunized rats were intraperitoneally challenged with wild-type ETEC H10407 to study the immune response in vivo. The serum titres of IgG and faecal IgA antibodies in the BI-CfaB plus BI-LTB mixed vaccination group were significantly greater than those in the other two groups, which were immunized with a single vaccine (P<0.05). However, no significant difference was seen between the two groups that received a single immunization. These results suggest that expressing CfaB and LTB in BI provides a probiotic system with immunogenic properties. Furthermore, the expression of LTB in BI preserved its mucosal adjuvant effect. So this study confirms that BI can be used as a novel oral vaccine expression system for a heterologous antigen and BI-LTB can provide mucosal adjuvant properties. PMID- 22053006 TI - Antimicrobial peptaibols from Trichoderma pseudokoningii induce programmed cell death in plant fungal pathogens. AB - Antibiosis is one of the widespread strategies used by Trichoderma spp. against plant fungal pathogens, the mechanism of which, however, remains poorly understood. Peptaibols are a large family of antimicrobial peptides produced by Trichoderma spp. Our previous study showed that trichokonins, a type of peptaibol from Trichoderma pseudokoningii SMF2, exhibited antibiotic activities against plant fungal pathogens. In this study, we first demonstrated that trichokonin VI (TK VI) induced extensive apoptotic programmed cell death in plant fungal pathogens. For a deeper insight into the apoptotic mechanism involved in the action of TK VI, Fusarium oxysporum was used as a model. Cells of F. oxysporum treated with TK VI showed apoptotic hallmarks, such as exposure of phosphatidylserine, the appearance of reactive oxygen species and fragmentation of nuclear DNA. Moreover, TK VI-treated cells exhibited an accumulation of cytoplasmic vacuoles with loss of the mitochondrial transmembrane potential, and this process was independent of metacaspases. Therefore, TK VI induces metacaspase-independent apoptotic cell death in F. oxysporum. This represents what is believed to be the first report to reveal the antibiotic mechanism of peptaibols against plant fungal pathogens. PMID- 22053007 TI - The putative phosphatase All1758 is necessary for normal growth, cell size and synthesis of the minor heterocyst-specific glycolipid in the cyanobacterium Anabaena sp. strain PCC 7120. AB - The filamentous cyanobacterium Anabaena sp. strain PCC 7120 differentiates nitrogen-fixing heterocysts arranged in a periodic pattern when deprived of a fixed source of nitrogen. In a genetic screen for mutations that prevent diazotrophic growth, open reading frame all1758, which encodes a putative serine/threonine phosphatase, was identified. Mutation of all1758 resulted in a number of seemingly disparate phenotypes that included a delay in the morphological differentiation of heterocysts, reduced cell size, and lethality under certain conditions. The mutant was incapable of fixing nitrogen under either oxic or anoxic conditions, and lacked the minor heterocyst-specific glycolipid. Pattern formation, as indicated by the timing and pattern of expression from the promoters of hetR and patS fused transcriptionally to the gene for green fluorescent protein (GFP), was unaffected by mutation of all1758, suggesting that its role in the formation of heterocysts is limited to morphological differentiation. Transcription of all1758 was constitutive with respect to both cell type and conditions of growth, but required a functional copy of all1758. The reduced cell size of the all1758 mutant and the location of all1758 between the cell division genes ftsX and ftsY may be indicative of a role for all1758 in cell division. Taken together, these results suggest that the protein encoded by all1758 may represent a link between cell growth, division and regulation of the morphological differentiation of heterocysts. PMID- 22053008 TI - Role of a short light, oxygen, voltage (LOV) domain protein in blue light- and singlet oxygen-dependent gene regulation in Rhodobacter sphaeroides. AB - The facultatively photosynthetic bacterium Rhodobacter sphaeroides harbours an unusual light, oxygen, voltage (LOV) domain protein, RsLOV. While showing a characteristic photocycle, the protein lacks a C-terminal output domain, similar to PpSB2 in Pseudomonas putida. Oxygen tension and light quantity are the two factors mainly responsible for controlling the expression of photosynthesis genes in R. sphaeroides. Two photoreceptor proteins are known to be involved in this regulation: the intensively studied AppA protein and the more recently identified cryptochrome-like protein CryB. Here we show by transcriptome and physiological studies that RsLOV is also involved in the regulation of photosynthetic gene expression. Our data further hint at a connection between RsLOV, carbohydrate metabolism and chemotaxis, as well as with the cellular response to photooxidative stress. RsLOV affects not only blue light-dependent gene expression but also redox-dependent regulation. PMID- 22053009 TI - The cargo and the transport system: secreted proteins and protein secretion in Trichoderma reesei (Hypocrea jecorina). AB - Trichoderma reesei (Hypocrea jecorina) is an efficient cell factory for protein production that is exploited by the enzyme industry. Yields of over 100 g secreted protein l(-1) from industrial fermentations have been reported. In this review we discuss the spectrum of proteins secreted by T. reesei and the studies carried out on its protein secretion system. The major enzymes secreted by T. reesei under production conditions are those degrading plant polysaccharides, the most dominant ones being the major cellulases, as demonstrated by the 2D gel analysis of the secretome. According to genome analysis, T. reesei has fewer genes encoding enzymes involved in plant biomass degradation compared with other fungi with sequenced genomes. We also discuss other T. reesei secreted enzymes and proteins that have been studied, such as proteases, laccase, tyrosinase and hydrophobins. Investigation of the T. reesei secretion pathway has included molecular characterization of the pathway components functioning at different stages of the secretion process as well as analysis of the stress responses caused by impaired folding or trafficking in the pathway or by expression of heterologous proteins. Studies on the transcriptional regulation of the secretory pathway have revealed similarities, but also interesting differences, with other organisms, such as a different induction mechanism of the unfolded protein response and the repression of genes encoding secreted proteins under secretion stress conditions. PMID- 22053011 TI - Understanding the human brain. PMID- 22053010 TI - Inhibition of p38 MAPK-dependent excision repair cross-complementing 1 expression decreases the DNA repair capacity to sensitize lung cancer cells to etoposide. AB - Etoposide (VP-16), a topoisomerase II inhibitor, is an effective anticancer drug currently used for the treatment of a wide range of cancers. Excision repair cross-complementary 1 (ERCC1) is a key protein involved in the process of nucleotide excision repair. High level of ERCC1 expression in cancers is associated with resistance to DNA damage-based chemotherapy. In this study, the effects of p38 mitogen-activated protein kinase (MAPK) signal on the ERCC1 expression induced by etoposide in non-small cell lung cancer (NSCLC) cell lines was investigated. Etoposide increased phosphorylated MAPK kinase 3/6 (MKK3/6)-p38 MAPK and ERCC1 protein and mRNA levels in A549 and H1975 cells. Moreover, SB202190, a p38 inhibitor, or knockdown of p38 expression by specific short interfering RNA (siRNA) significantly decreased the etoposide-induced ERCC1 protein levels and DNA repair capacity in etoposide-exposed NSCLC cells. Enhancement of p38 activation by constitutively active MKK6 (MKK6E) increased ERCC1 protein levels. Specific inhibition of ERCC1 by siRNA significantly enhanced the etoposide-induced cytotoxicity and hypoxanthine guanine phosphoribosyltransferase (hprt) gene mutation rate. Moreover, the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) could decrease the etoposide-induced p38 MAPK-mediated ERCC1 expression and augment the cytotoxic effect and growth inhibition by etopsoside. 17-AAG and etoposide-induced synergistic cytotoxic effect and DNA repair capacity decrease could be abrogated in lung cancer cells with MKK6E or HA-p38 MAPK expression vector transfection. Our results suggest that in human NSCLC cells, ERCC1 is induced by etoposide through the p38 MAPK pathway, and this phenomenon is required for NSCLC survival and resistant DNA damage. PMID- 22053016 TI - Bioterror research. Panel endorses anthrax vaccine study in children. PMID- 22053017 TI - Neuroscience. The brain's social network. PMID- 22053018 TI - Scientific misconduct. Psychologist accused of fraud on 'astonishing scale'. PMID- 22053019 TI - Epidemiology. Large African TB study reveals powerful strategy to curb disease. PMID- 22053020 TI - 12th International Congress of Human Genetics. Life on the fertile frontier. PMID- 22053021 TI - 12th International Congress of Human Genetics. X-tra diversity for Africans. PMID- 22053022 TI - 12th International Congress of Human Genetics. Diabetes genes decline out of Africa. PMID- 22053023 TI - Geophysics. Vigil at North Korea's Mount Doom. PMID- 22053024 TI - Geophysics. A very big bang. PMID- 22053025 TI - Profile: Robert Trivers. Sharp insights and a sharp tongue. PMID- 22053026 TI - Conservation: limits of land sparing. PMID- 22053027 TI - Conservation: model management intensity. PMID- 22053029 TI - Comment on "Atmospheric PCO2 perturbations associated with the Central Atlantic Magmatic Province". AB - Schaller et al. (Research Article, 18 March 2011, p. 1404) proposed that carbon dioxide (CO(2)) released by the Central Atlantic Magmatic Province eruptions over periods of about 20,000 years led to substantial increases of up to 2000 parts per million (ppm) in the concentration of atmospheric carbon dioxide (PCO(2)) near the Triassic-Jurassic boundary. Use of an atmosphere-ocean model coupled to a carbon-cycle model predicts PCO(2) increases of less than 400 ppm from magmatic volatiles, with only a small climatic impact. PMID- 22053032 TI - Sustainability. Paying for ecosystem services--promise and peril. PMID- 22053033 TI - Neuroscience. Another reason to exercise. PMID- 22053034 TI - Applied physics. Paradigm shifts in dye-sensitized solar cells. PMID- 22053035 TI - Neuroscience. Synaptic switch and social status. PMID- 22053036 TI - Applied physics. A photothermoelectric effect in graphene. PMID- 22053037 TI - Cell biology. Growth signaling from inside. PMID- 22053038 TI - Atmospheric science. Ocean effects of blocking. PMID- 22053039 TI - Climate. Running out of climate space. PMID- 22053040 TI - Eppendorf winner. The language of dendrites. PMID- 22053041 TI - The big and the small: challenges of imaging the brain's circuits. AB - The relation between the structure of the nervous system and its function is more poorly understood than the relation between structure and function in any other organ system. We explore why bridging the structure-function divide is uniquely difficult in the brain. These difficulties also explain the thrust behind the enormous amount of innovation centered on microscopy in neuroscience. We highlight some recent progress and the challenges that remain. PMID- 22053042 TI - The cell biology of synaptic plasticity. AB - Synaptic plasticity is the experience-dependent change in connectivity between neurons that is believed to underlie learning and memory. Here, we discuss the cellular and molecular processes that are altered when a neuron responds to external stimuli, and how these alterations lead to an increase or decrease in synaptic connectivity. Modification of synaptic components and changes in gene expression are necessary for many forms of plasticity. We focus on excitatory neurons in the mammalian hippocampus, one of the best-studied model systems of learning-related plasticity. PMID- 22053043 TI - Porphyrin-sensitized solar cells with cobalt (II/III)-based redox electrolyte exceed 12 percent efficiency. AB - The iodide/triiodide redox shuttle has limited the efficiencies accessible in dye sensitized solar cells. Here, we report mesoscopic solar cells that incorporate a Co((II/III))tris(bipyridyl)-based redox electrolyte in conjunction with a custom synthesized donor-pi-bridge-acceptor zinc porphyrin dye as sensitizer (designated YD2-o-C8). The specific molecular design of YD2-o-C8 greatly retards the rate of interfacial back electron transfer from the conduction band of the nanocrystalline titanium dioxide film to the oxidized cobalt mediator, which enables attainment of strikingly high photovoltages approaching 1 volt. Because the YD2-o-C8 porphyrin harvests sunlight across the visible spectrum, large photocurrents are generated. Cosensitization of YD2-o-C8 with another organic dye further enhances the performance of the device, leading to a measured power conversion efficiency of 12.3% under simulated air mass 1.5 global sunlight. PMID- 22053044 TI - A fluoride-derived electrophilic late-stage fluorination reagent for PET imaging. AB - The unnatural isotope fluorine-18 ((18)F) is used as a positron emitter in molecular imaging. Currently, many potentially useful (18)F-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of (18)F requires rapid syntheses for which [(18)F]fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment. However, conventional [(18)F]fluoride chemistry has been limited to nucleophilic fluorination reactions. We report the development of a palladium-based electrophilic fluorination reagent derived from fluoride and its application to the synthesis of aromatic (18)F-labeled molecules via late-stage fluorination. Late-stage fluorination enables the synthesis of conventionally unavailable positron emission tomography (PET) tracers for anticipated applications in pharmaceutical development as well as preclinical and clinical PET imaging. PMID- 22053045 TI - The pace of shifting climate in marine and terrestrial ecosystems. AB - Climate change challenges organisms to adapt or move to track changes in environments in space and time. We used two measures of thermal shifts from analyses of global temperatures over the past 50 years to describe the pace of climate change that species should track: the velocity of climate change (geographic shifts of isotherms over time) and the shift in seasonal timing of temperatures. Both measures are higher in the ocean than on land at some latitudes, despite slower ocean warming. These indices give a complex mosaic of predicted range shifts and phenology changes that deviate from simple poleward migration and earlier springs or later falls. They also emphasize potential conservation concerns, because areas of high marine biodiversity often have greater velocities of climate change and seasonal shifts. PMID- 22053046 TI - Atmospheric blocking and Atlantic multidecadal ocean variability. AB - Atmospheric blocking over the northern North Atlantic, which involves isolation of large regions of air from the westerly circulation for 5 days or more, influences fundamentally the ocean circulation and upper ocean properties by affecting wind patterns. Winters with clusters of more frequent blocking between Greenland and western Europe correspond to a warmer, more saline subpolar ocean. The correspondence between blocked westerly winds and warm ocean holds in recent decadal episodes (especially 1996 to 2010). It also describes much longer time scale Atlantic multidecadal ocean variability (AMV), including the extreme pre greenhouse-gas northern warming of the 1930s to 1960s. The space-time structure of the wind forcing associated with a blocked regime leads to weaker ocean gyres and weaker heat exchange, both of which contribute to the warm phase of AMV. PMID- 22053047 TI - Long-term change in the nitrogen cycle of tropical forests. AB - Deposition of reactive nitrogen (N) from human activities has large effects on temperate forests where low natural N availability limits productivity but is not known to affect tropical forests where natural N availability is often much greater. Leaf N and the ratio of N isotopes (delta(15)N) increased substantially in a moist forest in Panama between ~1968 and 2007, as did tree-ring delta(15)N in a dry forest in Thailand over the past century. A decade of fertilization of a nearby Panamanian forest with N caused similar increases in leaf N and delta(15)N. Therefore, our results indicate regional increases in N availability due to anthropogenic N deposition. Atmospheric nitrogen dioxide measurements and increased emissions of anthropogenic reactive N over tropical land areas suggest that these changes are widespread in tropical forests. PMID- 22053048 TI - Neural mechanisms for the coordination of duet singing in wrens. AB - Plain-tailed wrens (Pheugopedius euophrys) cooperate to produce a duet song in which males and females rapidly alternate singing syllables. We examined how sensory information from each wren is used to coordinate singing between individuals for the production of this cooperative behavior. Previous findings in nonduetting songbird species suggest that premotor circuits should encode each bird's own contribution to the duet. In contrast, we find that both male and female wrens encode the combined cooperative output of the pair of birds. Further, behavior and neurophysiology show that both sexes coordinate the timing of their singing based on feedback from the partner and suggest that females may lead the duet. PMID- 22053049 TI - Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. AB - The symbiotic microbiota profoundly affect many aspects of host physiology; however, the molecular mechanisms underlying host-microbe cross-talk are largely unknown. Here, we show that the pyrroloquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) activity of a commensal bacterium, Acetobacter pomorum, modulates insulin/insulin-like growth factor signaling (IIS) in Drosophila to regulate host homeostatic programs controlling developmental rate, body size, energy metabolism, and intestinal stem cell activity. Germ-free animals monoassociated with PQQ-ADH mutant bacteria displayed severe deregulation of developmental and metabolic homeostasis. Importantly, these defects were reversed by enhancing host IIS or by supplementing the diet with acetic acid, the metabolic product of PQQ-ADH. PMID- 22053050 TI - mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. AB - The mTOR complex 1 (mTORC1) protein kinase is a master growth regulator that is stimulated by amino acids. Amino acids activate the Rag guanosine triphosphatases (GTPases), which promote the translocation of mTORC1 to the lysosomal surface, the site of mTORC1 activation. We found that the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1. The v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome. In a cell-free system, ATP hydrolysis by the v-ATPase was necessary for amino acids to regulate the v-ATPase-Ragulator interaction and promote mTORC1 translocation. Results obtained in vitro and in human cells suggest that amino acid signaling begins within the lysosomal lumen. These results identify the v-ATPase as a component of the mTOR pathway and delineate a lysosome-associated machinery for amino acid sensing. PMID- 22053051 TI - RNAP II CTD phosphorylated on threonine-4 is required for histone mRNA 3' end processing. AB - The RNA polymerase II (RNAP II) largest subunit contains a C-terminal domain (CTD) with up to 52 Tyr(1)-Ser(2)-Pro(3)-Thr(4)-Ser(5)-Pro(6)-Ser(7) consensus repeats. Serines 2, 5, and 7 are known to be phosphorylated, and these modifications help to orchestrate the interplay between transcription and processing of messenger RNA (mRNA) precursors. Here, we provide evidence that phosphorylation of CTD Thr(4) residues is required specifically for histone mRNA 3' end processing, functioning to facilitate recruitment of 3' processing factors to histone genes. Like Ser(2), Thr(4) phosphorylation requires the CTD kinase CDK9 and is evolutionarily conserved from yeast to human. Our data thus illustrate how a CTD modification can play a highly specific role in facilitating efficient gene expression. PMID- 22053052 TI - Drosophila CENH3 is sufficient for centromere formation. AB - CENH3 is a centromere-specific histone H3 variant essential for kinetochore assembly. Despite its central role in centromere function, there has been no conclusive evidence supporting CENH3 as sufficient to determine centromere identity. To address this question, we artificially targeted Drosophila CENH3 (CENP-A/CID) as a CID-GFP-LacI fusion protein to stably integrated lac operator (lacO) arrays. This ectopic CID focus assembles a functional kinetochore and directs incorporation of CID molecules without the LacI-anchor, providing evidence for the self-propagation of the epigenetic mark. CID-GFP-LacI-bound extrachromosomal lacO plasmids can assemble kinetochore proteins and bind microtubules, resulting in their stable transmission for several cell generations even after eliminating CID-GFP-LacI. We conclude that CID is both necessary and sufficient to serve as an epigenetic centromere mark and nucleate heritable centromere function. PMID- 22053054 TI - Social network size affects neural circuits in macaques. AB - It has been suggested that variation in brain structure correlates with the sizes of individuals' social networks. Whether variation in social network size causes variation in brain structure, however, is unknown. To address this question, we neuroimaged 23 monkeys that had been living in social groups set to different sizes. Subject comparison revealed that living in larger groups caused increases in gray matter in mid-superior temporal sulcus and rostral prefrontal cortex and increased coupling of activity in frontal and temporal cortex. Social network size, therefore, contributes to changes both in brain structure and function. The changes have potential implications for an animal's success in a social context; gray matter differences in similar areas were also correlated with each animal's dominance within its social network. PMID- 22053053 TI - Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. AB - Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by expansion of a translated CAG repeat in Ataxin-1 (ATXN1). To determine the long-term effects of exercise, we implemented a mild exercise regimen in a mouse model of SCA1 and found a considerable improvement in survival accompanied by up regulation of epidermal growth factor and consequential down-regulation of Capicua, which is an ATXN1 interactor. Offspring of Capicua mutant mice bred to SCA1 mice showed significant improvement of all disease phenotypes. Although polyglutamine-expanded Atxn1 caused some loss of Capicua function, further reduction of Capicua levels--either genetically or by exercise--mitigated the disease phenotypes by dampening the toxic gain of function. Thus, exercise might have long-term beneficial effects in other ataxias and neurodegenerative diseases. PMID- 22053055 TI - Macrophages regulate expression of alpha1,2-fucosyltransferase genes in human endometrial epithelial cells. AB - The epithelial cell surface of the endometrium undergoes substantial biochemical changes to allow embryo attachment and implantation in early pregnancy. We hypothesized that tissue macrophages influence these events to promote uterine receptivity. To investigate the role of macrophages in regulating epithelial cell expression of genes linked to glycan-mediated embryo adhesion, Ishikawa, RL95-2 and HEC1A endometrial epithelial cells were cultured alone or with unactivated or lipopolysaccharide-activated monocytic U937 cells, separated using transwell inserts. Expression of mRNAs encoding two alpha1,2-fucosyltransferases (FUT1, FUT2) was increased in all three epithelial cell lines following co-culture with U937 cells, and was associated with increased fucosylation of cell surface glycoproteins detected using lectins from Ulex europaeus (UEA-1) and Dolichos biflorus (DBA). FUT1 induction by U937 cells also occurred in primary endometrial epithelial cells collected in luteal but not proliferative phase. Activation of the interleukin-6 (IL6)/leukemia inhibitory factor (LIF) cytokine signaling pathway with phosphorylation of STAT3 and elevated SOCS3 mRNA expression was evident in epithelial cells stimulated by U937 co-culture. Several recombinant macrophage-secreted cytokines exerted stimulatory or inhibitory effects on FUT1 and FUT2 mRNA expression, and the macrophage-derived cytokine LIF partially replicated the effects of U937 cells on both FUT1 and FUT2 expression and UEA-1 and DBA lectin reactivity in Ishikawa cells. These results suggest that macrophage-derived factors including LIF might facilitate development of an implantation-receptive endometrium by regulating surface glycan structures in epithelial cells. Abnormal phenotypes or altered abundance of uterine macrophages could contribute to the pathophysiology of primary unexplained infertility in women. PMID- 22053056 TI - Calcium signaling in mouse oocyte maturation: the roles of STIM1, ORAI1 and SOCE. AB - Calcium handling is critical for the oocyte function, since the first steps of fertilization are dependent on the appropriate Ca(2+) mobilization to originate transient spikes of the cytosolic Ca(2+) concentration. It is well known that the Ca(2+) influx from the extracellular milieu is required to maintain this signaling in mammalian oocytes. However, the regulation of the Ca(2+) channels involved in this process is still unknown in oocytes. STIM1, a key regulator of store-operated Ca(2+) entry (SOCE), relocates in the mouse oocyte shortly after sperm stimulation, suggesting that SOCE is involved in the maintenance of cytosolic Ca(2+)-spiking in the fertilized oocyte. Here, we show that there is an up-regulation of the expression of STIM1 at the germinal vesicle breakdown stage, and this expression remains steady during following maturation stages. We found that oocytes express ORAI1, a store-operated Ca(2+) channel, and that ORAI1 expression level was stable during oocyte maturation. Immature oocytes showed no Ca(2+) entry and no increase in STIM1-ORAI1 colocalization in response to the store depletion induced by thapsigargin. On the contrary, in mature oocytes, STIM1-ORAI1 colocalization is enhanced 3-fold by depletion of Ca(2+) stores, enabling the activation of store-operated calcium channels and therefore Ca(2+) entry. Finally, the correlation between SOCE activation during the maturation of oocytes and STIM1-ORAI1 colocalization strongly suggests that ORAI1 is involved in the Ca(2+) entry pathway in the mature oocyte. SOCE up-regulation in the final stage of maturation is further evidence of a major role for SOCE in fully mature oocytes, and therefore in Ca(2+) signaling at fertilization. PMID- 22053057 TI - MicroRNA regulation via DNA methylation during the morula to blastocyst transition in mice. AB - Epigenetic regulation is responsible for transcriptional silencing of genes and parental imprinting. This study addresses the question whether microRNAs (miRNAs) could be affected by DNA methylation during morula-blastocyst transition. Mouse embryos were treated with/without a DNA methyltransferase inhibitor (5-aza-2' deoxycytidine, 5-aza-dC, 10 nM-5 MUM). Changes of miRNAs were analyzed by quantitative real-time (Q-PCR)-based megaplex pre-amp microRNA assays. Development from morula to blastocyst in mice was inhibited by 5-aza-dC in a dose dependent manner (10 nM-5 MUM), with half of the embryos arrested at morula stage when treated with levels of 5-aza-dC as low as 50 nM. In total, 48 down-regulated microRNAs and 17 up-regulated microRNAs (>=5-fold changes) were identified after 5-aza-dC treatment, including let-7e, mir-20a, mir-21, mir-34b, mir-128b and mir 452. Their predicted targets were selected based on software analysis, published databases and further confirmed by Q-PCR. At least eight targets, including dnmt3a, jagged 1, sp1, edg2, abcg4, numa1, tmsb10 and csf1r were confirmed. In conclusion, 5-aza-dC-modified microRNA profiles and identification of the microRNA's targets during the morula to blastocyst stage in mice provide information that helps us to explore the relationship between fertility, microRNA regulation and epigenetic intervention. PMID- 22053058 TI - Cancer-preventive rexinoid modulates neutral lipid contents of mammary epithelial cells through a peroxisome proliferator-activated receptor gamma-dependent mechanism. AB - Synthetic rexinoids effectively suppress both estrogen receptor-positive and estrogen receptor-negative mammary tumors in animal models, which makes them prime candidates for a novel class of cancer-preventive agents. When used in combination with chemotherapy for non-small-cell lung cancer, the rexinoid bexarotene was most effective for patients who developed hypertriglyceridemia as a side effect. Although serum triglycerides originate from the liver, the effect of bexarotene on lipogenesis in breast epithelial cells is not known. Gene expression studies with normal mammary epithelial cells indicated that rexinoids modulate lipid metabolism, particularly enzymes involved in triglyceride synthesis. High-content analysis revealed dose-dependent accumulation of neutral lipids within adipocyte differentiation-related protein-associated cytoplasmic lipid droplets after long-term bexarotene treatment. Bexarotene also induced mRNA and protein levels for peroxisome proliferator-activated receptor (PPAR) gamma, whereas selective knockdown of PPARgamma attenuated the induction of both lipid droplets and adipocyte differentiation-related protein. Pharmacological activation of PPARgamma, but not PPARalpha or retinoic acid receptors, effectively induced lipid accumulation. Furthermore, the combination of the PPARgamma agonist rosiglitazone with bexarotene synergistically suppressed the growth of human mammary epithelial cells and revealed a strong, nonlinear, inverse correlation of cell growth with lipid droplet accumulation in the cell population. These findings indicate that rexinoids activate a lipogenic program in mammary epithelial cells through a retinoid X receptor/PPARgamma-mediated mechanism. It is noteworthy that combining low doses of bexarotene with the PPARgamma agonist rosiglitazone provides effective growth suppression of mammary epithelial cells, potentially dissociating systemic adverse effects associated with standard bexarotene treatment from the antiproliferative effects on mammary epithelium. PMID- 22053059 TI - Shared learning for chronic conditions: a methodology for developing the Royal College of Paediatrics and Child Health (RCPCH) care pathways for children with allergies. AB - AIMS: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies. The pathways focus on defining the competences to deliver the highest standard of care for such children. By defining competences rather than criteria for onward referral, the authors have sought to create flexibility in delivery of care which will be responsive to regional variations in knowledge, skills and service. METHOD: All pathways were developed by multidisciplinary working groups, based on a comprehensive review of evidence. The pathways were reviewed by a broad group of stakeholders and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. RESULTS: The results for all pathways are presented in two sections: a pathway algorithm and the competences. The entry points for each pathway are defined at the point where symptoms first occur and the ideal management is described from self-care through complete diagnosis to monitoring of progress. From the evidence review the working groups were able to make research recommendations. CONCLUSIONS: The authors present eight national care pathways for allergic conditions based on evidence review, expert consensus and stakeholder input. They provide a guide for training and development of services to facilitate improvements in delivery as close to the patient's home as possible. The authors recommend that these pathways are implemented locally by a multidisciplinary team with a focus on creating networks between primary, secondary and tertiary care to improve services for children with allergic conditions. PMID- 22053060 TI - The 'unified airway': the RCPCH care pathway for children with asthma and/or rhinitis. AB - AIMS: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies: the asthma/rhinitis care pathway is the third such pathway. Asthma and rhinitis have been considered together. These conditions co-exist commonly, have remarkably similar immuno pathology and an integrated management approach benefits symptom control. METHOD: The asthma/rhinitis pathway was developed by a multidisciplinary working group and was based on a comprehensive review of evidence. The pathway was reviewed by a broad group of stakeholders including the public and was approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. RESULTS: The pathway entry points are defined by symptom type and severity at presentation. Acute severe rhinitis and life-threatening asthma are presented as distinct entry routes to the pathway, recognising that initial care of these conditions requires presentation-specific treatments. However, the pathway emphasises that ideal long term care should take account of both conditions in order to achieve maximal improvements in disease control and quality of life. CONCLUSIONS: The pathway recommends that acute presentations of asthma and/or rhinitis should be treated separately. Where both conditions exist, ongoing management should address the upper and lower airways. The authors recommend that this pathway is implemented locally by a multidisciplinary team (MDT) with a focus on creating networks. The MDT within these networks should work with patients to develop and agree on care plans that are age and culturally appropriate. PMID- 22053061 TI - The RCPCH care pathway for children with drug allergies: an evidence and consensus based national approach. AB - AIMS: The Royal College of Paediatrics and Child Health (RCPCH) was commissioned by the Department of Health to develop a drug allergy pathway. It focuses on defining the competences to improve the equity of care received by children. METHOD: The drug pathway was developed by a multidisciplinary working group and was based on a comprehensive review of evidence. The team decided to focus on IgE mediated reactions as these have the greatest potential to be life-threatening. RESULTS: The results are presented in four parts: evidence review, pathway mapping, external review and core knowledge documents. The evidence review found a high percentage of putative penicillin allergy is not confirmed by objective testing and that resensitisation to beta-lactam drugs was infrequent. It also highlighted the importance of a detailed history and accurate diagnosis along with clear communication of test results to both family and primary care. CONCLUSIONS: This pathway demonstrates the spectrum of drug allergy is varied and may differ for young children compared with older children and adults. The authors highlight the paucity of evidence to support allergy testing for most drugs, in children, other than supervised incremental provocation tests (when indicated). Acute presentations require emergency health professionals to address underlying allergic issues, including recognition and avoidance of potential drug allergy triggers. Non-acute presentations may include multi-system symptoms which may have a broad differential diagnosis; this document signposts to the relevant partners in the RCPCH care pathway portfolio. Management combines a care package including a definitive diagnosis, initiating treatments and ongoing education. PMID- 22053062 TI - Emollients, education and quality of life: the RCPCH care pathway for children with eczema. AB - OBJECTIVES: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies. The eczema pathway focuses on defining the competences to improve the equity of care received by children with eczema. METHOD: The eczema pathway was developed by a multidisciplinary working group and was based on a comprehensive review of evidence. The pathway was reviewed by a broad group of stakeholders including paediatricians, allergists, dermatologists, specialist nurses, dietician, patients' representatives and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. It was also reviewed by a wide range of stakeholders. RESULTS: The results are presented in three sections: the evidence review, mapping and the core knowledge document. The various entry points to the ideal pathway of care are defined from self-care through to follow-up. There is considerable emphasis on good skin care and when allergy problems should be dealt with. The pathway algorithm and associated competences can be downloaded from http://www.rcpch.ac.uk/allergy/eczema. CONCLUSIONS: Effective eczema management is holistic and encompasses an assessment of severity and impact on quality of life, treatment of the inflamed epidermal skin barrier, recognition and treatment of infection and assessment and management of environmental and allergy triggers. Patient and family education which seeks to maximise understanding and concordance with treatment is also important in all children with eczema. PMID- 22053063 TI - The RCPCH care pathway for food allergy in children: an evidence and consensus based national approach. AB - AIMS: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies; food allergy is the second pathway. The pathways focus on defining the competences required to improve the equity of care received by children with allergic conditions. METHOD: The food allergy pathway was developed by a multidisciplinary working group and was based on a comprehensive review of the evidence. The pathway was reviewed by a broad group of stakeholders including the public and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. The National Institute of Health and Clinical Excellence simultaneously established a short guideline review of community practice for children with food allergy; close communication was established between the two groups. RESULTS: The results are presented in two sections: a pathway algorithm and the competences. The entry points are defined and the ideal pathway of care is described from initial recognition and confirmed diagnosis through to follow-up. CONCLUSIONS: The range of manifestations of food allergy/intolerance is much more diverse than hitherto recognised and diagnosis can be problematic as many patients do not have classical IgE mediated disease. The pathway provides a guide for training and development of services to facilitate improvements in delivery as close to the patient's home as possible. The authors recommend that this pathway is implemented locally by a multidisciplinary team with a focus on creating networks. PMID- 22053064 TI - The RCPCH care pathway for children with latex allergies: an evidence- and consensus-based national approach. AB - AIMS: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies; the latex allergy pathway is the seventh pathway. The pathways focus on defining the competences to improve the equity of care received by children with allergic conditions. METHOD: The RCPCH latex allergy pathway was developed by a multidisciplinary working group and was based on a comprehensive review of evidence. The pathway was reviewed by a broad group of stakeholders including the public and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. RESULTS: The results are presented in four parts, the evidence review, pathway mapping, external review and core knowledge documents. The evidence review highlighted the paucity of recent evidence for latex allergy in childhood. The review found that the diagnostic sensitivity of different latex extracts for skin-prick testing may differ. It also noted that health professionals should be aware of latex allergy, and care should be taken to avoid contact with latex in young infants, especially when there is a family history for latex allergy. The pathway entry points are defined by the severity at presentation. CONCLUSIONS: The latex allergy pathway provides a guide for training and development of services to facilitate improvements in delivery as close to the patients home as possible. The authors recommend that this pathway is implemented locally by a multidisciplinary team with a focus on creating networks between primary, secondary and tertiary care to improve services for children with allergic conditions. PMID- 22053065 TI - The RCPCH care pathway for children with urticaria, angio-oedema or mastocytosis: an evidence and consensus based national approach. AB - AIMS: The Royal College of Paediatrics and Child Health (RCPCH) Science and Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies; the urticaria, angio-oedema or mastocytosis pathway is the fifth pathway. The pathways focus on defining the competences required to improve the equity of care received by children with allergic conditions. METHOD: The urticaria, angio-oedema or mastocytosis pathway was developed by a multidisciplinary working group and was based on a comprehensive review of evidence. The pathway was reviewed by a broad group of stakeholders including the public and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. RESULTS: Three pathways are described: urticaria with or without angio-oedema, angio-oedema without weals, and mastocytosis. The results are presented in four parts: evidence review, mapping, external review and core knowledge documents. Acute urticaria has many causes and is often not allergic in origin. It is frequently of relatively short duration and easily managed with antihistamines alone. However, at the other extreme, causes of chronic urticaria and angio-oedema are difficult to diagnose and treatment can be complex. Thus defining the competence required for each extreme is critical to ensure optimal care. The evidence review identified that allergy testing and thyroid function testing were helpful in the investigation of chronic urticaria, that increasing the dose of antihistamine was effective in treating urticaria and that ciclosporin A and prednisolone were effective second line treatments. CONCLUSIONS: From the common presentation of acute (intermittent) urticaria to the uncommon presentations of chronic urticaria, angio-oedema and cutaneous mastocytosis, this pathway is a tool to assist health professionals to differentiate and manage these conditions. PMID- 22053066 TI - The RCPCH care pathway for children with venom allergies: an evidence and consensus based national approach. AB - AIMS: The Royal College of Paediatrics and Child Health (RCPCH) Science & Research Department was commissioned by the Department of Health to develop national care pathways for children with allergies; the venom allergy pathway is the seventh pathway. The pathways focus on defining the competences to improve the equity of care received by children with allergic conditions. METHOD: The RCPCH venom allergy pathway was developed by a multidisciplinary working group and was based on a comprehensive review of evidence. The pathway was reviewed by a broad group of stakeholders including the public and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. RESULTS: The pathway results are presented in four parts: evidence review, mapping, external review and core knowledge documents. The entry points are defined and the ideal pathway of care is described from self-care through to follow-up. The evidence highlighted that venom immunotherapy is safe and effective for bee and wasp allergy and that there are real quality of life benefits for patients. The review also highlighted the value of measuring serum tryptase after reactions. CONCLUSIONS: The venom allergy pathway provides a guide for training and development of services to facilitate improvements in delivery as close to the patient's home as possible. The authors recommend that this pathway should be implemented locally by a multidisciplinary team with a focus on creating networks between primary, secondary and tertiary care to improve services for children with allergic conditions. PMID- 22053067 TI - The RCPCH care pathway for children at risk of anaphylaxis: an evidence and consensus based national approach to caring for children with life-threatening allergies. AB - AIMS: Numerous studies have identified shortcomings in the management of children at risk of severe acute allergic reactions (anaphylaxis). The Science and Research Department at the Royal College of Paediatrics and Child Health (RCPCH) was commissioned by the Department of Health to develop competence based national care pathways for children with allergies. Anaphylaxis is the first completed pathway. METHODS: The anaphylaxis pathway was developed by a multidisciplinary working group, reviewed by a broad group of stakeholders and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. RESULTS: Pathway development is described under five headings: evidence review, mapping, external review, core knowledge documents and key recommendations. The full pathway can be downloaded from www.rcpch.ac.uk/allergy/anaphylaxis. This document describes the entry points and the ideal pathway of care from self-care through to follow-up. The five key recommendations focus on: (1) prompt administration of adrenaline by intramuscular injection; (2) referral to specialists with competence in paediatric allergies; (3) risk analysis; (4) provision of a self-management plan; and (5) suggested creation of a national anaphylaxis death register. CONCLUSIONS: We present the first national care pathway for anaphylaxis, which is based on a critique of published evidence, expert consensus and multi-stakeholder input including patient representation via the Anaphylaxis Campaign. The Project Board urges health professionals to work together across networks to improve care for children at risk of anaphylaxis, in particular during the period after an acute reaction. Additionally, the Project Board strongly recommends the funding of a national anaphylaxis register. PMID- 22053068 TI - Translating the theoretical into practical: a logical framework of functional analytic psychotherapy interactions for research, training, and clinical purposes. AB - Functional analytic psychotherapy (FAP) provides a behavioral analysis of the psychotherapy relationship that directly applies basic research findings to outpatient psychotherapy settings. Specifically, FAP suggests that a therapist's in vivo (i.e., in-session) contingent responding to targeted client behaviors, particularly positive reinforcement of a client's effective behavior, should be a powerful mechanism of change. However, much of the previous literature on FAP has been theoretical, broadly defining FAP techniques rather than explicating them with the precision necessary for replication and training. In this article, the authors explicate a logical framework for turn-by-turn interactions between the client and therapist that may guide research, training, and dissemination of FAP. This molecular behavioral description of the events of the proposed logical interaction lends itself to microprocess research methodology, and a discussion of potential hypotheses to explore follows. Prescriptive, direct guidance for the application of FAP for training and dissemination purposes is given. PMID- 22053069 TI - Physical activity in youth with well-controlled versus poorly controlled type 2 diabetes. AB - PURPOSE: Type 2 diabetes increases risk of chronic disease. The recommendations are for youth to attain at least 60 minutes of daily physical activity (PA). Fewer than 20% achieve this goal. This study examines differences between blood glucose control and PA in youth with type 2 diabetes. METHODS: A1c levels and PA were tested in youth 9 to 17 years old with newly diagnosed type 2 diabetes during clinic visits. Average daily minutes of moderate to vigorous physical activity (MVPA) was calculated. Differences in MVPA were investigated. RESULTS: Slightly more than half of youth had well-controlled diabetes. All engaged in less PA than recommended. Youth with well-controlled diabetes engaged in slightly less MVPA than those whose diabetes was not in control. There were no significant differences in minutes of MVPA by gender, race, or diabetes control. CONCLUSIONS: It is necessary to identify ways to increase PA among youth with type 2 diabetes. PMID- 22053070 TI - Determinants of microvascular network topologies in implanted neovasculatures. AB - OBJECTIVE: During neovascularization, the end result is a new functional microcirculation composed of a network of mature microvessels with specific topologies. Although much is known concerning the mechanisms underlying the initiation of angiogenesis, it remains unclear how the final architecture of microcirculatory beds is regulated. To begin to address this, we determined the impact of angiogenic neovessel prepatterning on the final microvascular network topology using a model of implant neovascularization. METHODS AND RESULTS: We used 3D direct-write bioprinting or physical constraints in a manner permitting postangiogenesis vascular remodeling and adaptation to pattern angiogenic microvascular precursors (neovessels formed from isolated microvessel segments) in 3D collagen gels before implantation and subsequent network formation. Neovasculatures prepatterned into parallel arrays formed functional networks after 4 weeks postimplantation but lost the prepatterned architecture. However, maintenance of uniaxial physical constraints during postangiogenesis remodeling of the implanted neovasculatures produced networks with aligned microvessels, as well as an altered proportional distribution of arterioles, capillaries, and venules. CONCLUSIONS: Here we show that network topology resulting from implanted microvessel precursors is independent from prepatterning of precursors but can be influenced by a patterning stimulus involving tissue deformation during postangiogenesis remodeling and maturation. PMID- 22053071 TI - Deleted in malignant brain tumors 1 is present in the vascular extracellular matrix and promotes angiogenesis. AB - OBJECTIVE: Deleted in malignant brain tumors 1 (DMBT1) belongs to the scavenger receptor cysteine-rich superfamily of proteins and is implicated in innate immunity, cell polarity, and differentiation. Here we studied the role of DMBT1 in endothelial cells. METHODS AND RESULTS: DMBT1 was secreted into the extracellular matrix (ECM) by endothelial cells in vitro and in situ and the presence of DMBT1 in the ECM increased endothelial cell adherence. Endothelial cell-derived DMBT1 associated with galectin-3 (coprecipitation), and human recombinant DMBT1 bound EGF, vascular endothelial growth factor and Delta-like (Dll) 4 (specific ELISAs). Compared to cells from wild-type mice, endothelial cells from DMBT1(-/-) mice demonstrated reduced migration, proliferation, and tube formation. In vivo recovery from hindlimb ischemia was attenuated in DMBT1( /-) animals as was vascular endothelial growth factor -induced endothelial sprouting from isolated aortic rings; the latter response could be rescued by the addition of recombinant DMBT1. The Notch pathway is involved in multiple aspects of vascular development, including arterial-venous differentiation and we found that endothelial cells from DMBT1(-/-) mice expressed more EphrinB2 than cells from wild-type mice. Levels of Dll1, Dll4, Hes1, Hey1, and EphB4, on the other hand, were decreased. CONCLUSIONS: Taken together, the results of this study indicate that DMBT1 functions as an important endothelium-derived ECM protein that is able to bind angiogenic factors and promote adhesion, migration, proliferation, and angiogenesis as well as vascular repair. Mechanistically, DMBT1 interacts with galectin-3 and modulates the Notch signaling pathway as well as the differential expression of ephrin-B2 and EphB4. PMID- 22053072 TI - Reperfusion injury intensifies the adaptive human T cell alloresponse in a human mouse chimeric artery model. AB - OBJECTIVE: Perioperative nonimmune injuries to an allograft can decrease graft survival. We have developed a model for studying this process using human materials. METHODS AND RESULTS: Human artery segments were transplanted as infrarenal aortic interposition grafts into an immunodeficient mouse host, allowed to "heal in" for 30 days, and then retransplanted into a second mouse host. To induce a reperfusion injury, the healed-in artery segments were incubated for 3 hours under hypoxic conditions ex vivo before retransplantation. To induce immunologic rejection, the animals receiving the retransplanted artery segment were adoptively transferred with human peripheral blood mononuclear cells or purified T cells from a donor allogeneic to the artery 1 week before surgery. To compare rejection of injured versus healthy tissues, these manipulations were combined. Results were analyzed ex vivo by histology, morphometry, immunohistochemistry, and mRNA quantitation or in vivo by ultrasound. Our results showed that reperfusion injury, which otherwise heals with minimal sequelae, intensifies the degree of allogeneic T cell-mediated injury to human artery segments. CONCLUSIONS: We developed a new human-mouse chimeric model demonstrating interactions of reperfusion injury and alloimmunity using human cells and tissues that may be adapted to study other forms of nonimmune injury and other types of adaptive immune responses. PMID- 22053073 TI - ApoE suppresses atherosclerosis by reducing lipid accumulation in circulating monocytes and the expression of inflammatory molecules on monocytes and vascular endothelium. AB - OBJECTIVE: We investigated atheroprotective properties of apolipoprotein (apo) E beyond its ability to lower plasma cholesterol. We hypothesized that apoE reduces atherosclerosis by decreasing lipid accumulation in circulating monocytes and the inflammatory state of monocytes and the vascular endothelium. METHODS AND RESULTS: We developed mice with spontaneous hyperlipidemia with and without plasma apoE. Hypomorphic apoE mice deficient in low-density lipoprotein receptor (Apoe(h/h)Ldlr(-/-)) were compared to Apoe(-/-)Ldlr(-/-) mice. Despite 4-fold more plasma apoE than WT mice, Apoe(h/h)Ldlr(-/-) mice displayed similar plasma cholesterol as Apoe(-/-) Ldlr(-/-) mice but developed 4-fold less atherosclerotic lesions by 5 months of age. The aortic arch of Apoe(h/h)Ldlr(-/-) mice showed decreased endothelial expression of ICAM-1, PECAM-1, and JAM-A. In addition, Apoe(h/h)Ldlr(-/-) mice had less circulating leukocytes and proinflammatory Ly6C(high) monocytes. These monocytes had decreased neutral lipid content and reduced surface expression of ICAM-1, VLA-4, and L-Selectin. Apoe(h/h)Ldlr(-/-) mice displayed increased levels of apoA1-rich HDL that were potent in promoting cellular cholesterol efflux. CONCLUSIONS: Our findings suggest that apoE reduces atherosclerosis in the setting of hyperlipidemia by increasing plasma apoA1-HDL that likely contribute to reduce intracellular lipid accumulation and thereby the activation of circulating leukocytes and the vascular endothelium. PMID- 22053074 TI - Rosiglitazone causes endothelial dysfunction in humans. AB - OBJECTIVES: We explored the impact of rosiglitazone on endothelial function in normal volunteers and its interaction with glyceryl trinitrate (GTN)-induced abnormalities in endothelial function. We hypothesized that rosiglitazone would have a neutral effect on endothelial function in normal volunteers and would favorably modify endothelial dysfunction induced by GTN. METHODS: In this double blind, randomized, placebo-controlled study, 44 participants were randomized to placebo, rosiglitazone (4 mg twice daily), transdermal GTN (0.6 mg/h), or both GTN and rosiglitazone. After 7 days of treatment, participants underwent measures of forearm blood flow during brachial artery infusion of acetylcholine (Ach). Serum glucose concentrations and insulin sensitivity were assessed. RESULTS: Unexpectedly, rosiglitazone-treated participants experienced blunted responses to endothelium-dependent responses to Ach (P < .05 vs placebo). Sustained GTN administration caused similar abnormalities in endothelial function (P < .05 vs placebo) and rosiglitazone + GTN (P < .05 vs placebo; P = ns vs rosiglitazone). Interestingly, co-infusion of the antioxidant vitamin C improved endothelial responses in those randomized to rosiglitazone and GTN alone (P = not significant [ns] compared with placebo), but it did not improve endothelial function in those treated with rosiglitazone + GTN. Neither rosiglitazone nor GTN treatment modified the measures of glucose metabolism. CONCLUSIONS: Unexpectedly, therapy with rosiglitazone caused abnormalities in endothelial function in normal volunteers. These findings have important implications with respect to drug development and surveillance. PMID- 22053075 TI - Gender differences in the psychological impact of tsunami. AB - AIM: The aim of this observational study was to explore gender-related differences in psychiatric morbidity during the initial three months following the December 2004 earthquake and tsunami involving the Andaman and Nicobar Islands, India. METHODS: There were 12,784 survivors sheltered across 74 relief camps with 4,684 displaced survivors in Port Blair and 8,100 non-displaced survivors in Car-Nicobar Island. All persons who accessed mental health assistance within the camps constituted the study sample. Diagnoses were made by qualified psychiatrists using the ICD-10. There were 475 patients: 188 (40%) men and 287 (60%) women. RESULTS: There were significant gender differences in terms of displacement. There were significantly higher levels of panic disorder, unspecified anxiety disorder and somatic complaints in the displaced women while the non-displaced population showed more adjustment disorder. CONCLUSIONS: Displacement was a significant factor in the manifestations of observed pathology. Displaced women had greater psychiatric morbidity. In addition, the fact that adjustment disorder (a self-limiting disorder form of psychopathology) was more prevalent in the non-displaced group may be a reflection of the findings of overall lesser morbidity in non-displaced women. Hence, women may have to be rehabilitated in their own habitats after major disasters. PMID- 22053076 TI - deepBlockAlign: a tool for aligning RNA-seq profiles of read block patterns. AB - MOTIVATION: High-throughput sequencing methods allow whole transcriptomes to be sequenced fast and cost-effectively. Short RNA sequencing provides not only quantitative expression data but also an opportunity to identify novel coding and non-coding RNAs. Many long transcripts undergo post-transcriptional processing that generates short RNA sequence fragments. Mapped back to a reference genome, they form distinctive patterns that convey information on both the structure of the parent transcript and the modalities of its processing. The miR-miR* pattern from microRNA precursors is the best-known, but by no means singular, example. RESULTS: deepBlockAlign introduces a two-step approach to align RNA-seq read patterns with the aim of quickly identifying RNAs that share similar processing footprints. Overlapping mapped reads are first merged to blocks and then closely spaced blocks are combined to block groups, each representing a locus of expression. In order to compare block groups, the constituent blocks are first compared using a modified sequence alignment algorithm to determine similarity scores for pairs of blocks. In the second stage, block patterns are compared by means of a modified Sankoff algorithm that takes both block similarities and similarities of pattern of distances within the block groups into account. Hierarchical clustering of block groups clearly separates most miRNA and tRNA, and also identifies about a dozen tRNAs clustering together with miRNA. Most of these putative Dicer-processed tRNAs, including eight cases reported to generate products with miRNA-like features in literature, exhibit read blocks distinguished by precise start position of reads. AVAILABILITY: The program deepBlockAlign is available as source code from http://rth.dk/resources/dba/. CONTACT: gorodkin@rth.dk; studla@bioinf.uni-leipzig.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22053077 TI - AMPA: an automated web server for prediction of protein antimicrobial regions. AB - SUMMARY: AMPA is a web application for assessing the antimicrobial domains of proteins, with a focus on the design on new antimicrobial drugs. The application provides fast discovery of antimicrobial patterns in proteins that can be used to develop new peptide-based drugs against pathogens. Results are shown in a user friendly graphical interface and can be downloaded as raw data for later examination. AVAILABILITY: AMPA is freely available on the web at http://tcoffee.crg.cat/apps/ampa. The source code is also available in the web. CONTACT: marc.torrent@upf.edu; david.andreu@upf.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22053078 TI - Detecting genome-wide epistases based on the clustering of relatively frequent items. AB - MOTIVATION: In genome-wide association studies (GWAS), up to millions of single nucleotide polymorphisms (SNPs) are genotyped for thousands of individuals. However, conventional single locus-based approaches are usually unable to detect gene-gene interactions underlying complex diseases. Due to the huge search space for complicated high order interactions, many existing multi-locus approaches are slow and may suffer from low detection power for GWAS. RESULTS: In this article, we develop a simple, fast and effective algorithm to detect genome-wide multi locus epistatic interactions based on the clustering of relatively frequent items. Extensive experiments on simulated data show that our algorithm is fast and more powerful in general than some recently proposed methods. On a real genome-wide case-control dataset for age-related macular degeneration (AMD), the algorithm has identified genotype combinations that are significantly enriched in the cases. AVAILABILITY: http://www.cs.ucr.edu/~minzhux/EDCF.zip CONTACT: minzhux@cs.ucr.edu; jingli@cwru.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22053079 TI - Tissue-specific alternative polyadenylation at the imprinted gene Mest regulates allelic usage at Copg2. AB - The gene Mest (also known as Peg1) is regulated by genomic imprinting in the mouse and only the paternal allele is active for transcription. MEST is similarly imprinted in humans, where it is a candidate for the growth retardation Silver Russell syndrome. The MEST protein belongs to an ancient family of hydrolases but its function is still unknown. It is highly conserved in vertebrates although imprinted expression is only observed in marsupials and eutherians, thus a recent evolutionary event. Here we describe the identification of new imprinted RNA products at the Mest locus, longer variants of the RNA, called MestXL, transcribed >10 kb into the downstream antisense gene Copg2. During development MestXL is produced exclusively in the developing central nervous system (CNS) by alternative polyadenylation. Copg2 is biallelically expressed in the embryo except in MestXL-expressing tissues, where we observed preferential expression from the maternal allele. To analyze the function of the MestXL transcripts in Copg2 regulation, we studied the effects of a targeted allele at Mest introducing a truncation in the mRNA. We show that both the formation of the MestXL isoforms and the allelic bias at Copg2 are lost in the CNS of mutants embryos. Our results propose a new mechanism to regulate allelic usage in the mammalian genome, via tissue-specific alternative polyadenylation and transcriptional interference in sense-antisense pairs at imprinted loci. PMID- 22053080 TI - Crystal structure of Hfq from Bacillus subtilis in complex with SELEX-derived RNA aptamer: insight into RNA-binding properties of bacterial Hfq. AB - Bacterial Hfq is a protein that plays an important role in the regulation of genes in cooperation with sRNAs. Escherichia coli Hfq (EcHfq) has two or more sites that bind RNA(s) including U-rich and/or the poly(A) tail of mRNA. However, functional and structural information about Bacillus subtilis Hfq (BsHfq) including the RNA sequences that specifically bind to it remain unknown. Here, we describe RNA aptamers including fragment (AG)(3)A that are recognized by BsHfq and crystal structures of the BsHfq-(AG)(3)A complex at 2.2 A resolution. Mutational and structural studies revealed that the RNA fragment binds to the distal site, one of the two binding sites on Hfq, and identified amino acid residues that are critical for sequence-specific interactions between BsHfq and (AG)(3)A. In particular, R32 appears to interact with G bases in (AG)(3)A. Poly(A) also binds to the distal site of EcHfq, but the overall RNA structure and protein-RNA interaction patterns engaged in the R32 residues of BsHfq-(AG)(3)A differ from those of EcHfq-poly(A). These findings provide novel insight into how the Hfq homologue recognizes RNA. PMID- 22053081 TI - Upregulation of Cyclin B1 by miRNA and its implications in cancer. AB - It is largely recognized that microRNAs (miRNAs) function to silence gene expression by targeting 3'UTR regions. However, miRNAs have also been implicated to positively-regulate gene expression by targeting promoter elements, a phenomenon known as RNA activation (RNAa). In the present study, we show that expression of mouse Cyclin B1 (Ccnb1) is dependent on key factors involved in miRNA biogenesis and function (i.e. Dicer, Drosha, Ago1 and Ago2). In silico analysis identifies highly-complementary sites for 21 miRNAs in the Ccnb1 promoter. Experimental validation identified three miRNAs (miR-744, miR-1186 and miR-466d-3p) that induce Ccnb1 expression in mouse cell lines. Conversely, knockdown of endogenous miR-744 led to decreased Ccnb1 levels. Chromatin immunoprecipitation (ChIP) analysis revealed that Ago1 was selectively associated with the Ccnb1 promoter and miR-744 increased enrichment of RNA polymerase II (RNAP II) and trimethylation of histone 3 at lysine 4 (H3K4me3) at the Ccnb1 transcription start site. Functionally, short-term overexpression of miR-744 and miR-1186 resulted in enhanced cell proliferation, while prolonged expression caused chromosomal instability and in vivo tumor suppression. Such phenotypes were recapitulated by overexpression of Ccnb1. Our findings reveal an endogenous system by which miRNA functions to activate Ccnb1 expression in mouse cells and manipulate in vivo tumor development/growth. PMID- 22053082 TI - Highly organized DnaA-oriC complexes recruit the single-stranded DNA for replication initiation. AB - In Escherichia coli, the replication origin oriC consists of two functional regions: the duplex unwinding element (DUE) and its flanking DnaA-assembly region (DAR). ATP-DnaA molecules multimerize on DAR, unwinding DUE for DnaB helicase loading. However, DUE-unwinding mechanisms and functional structures in DnaA-oriC complexes supporting those remain unclear. Here, using various in vitro reconstituted systems, we identify functionally distinct DnaA sub-complexes formed on DAR and reveal novel mechanisms in DUE unwinding. The DUE-flanking left half DAR carrying high-affinity DnaA box R1 and the ATP-DnaA-preferential DnaA box R5, tau1-2 and I1-2 sites formed a DnaA sub-complex competent in DUE unwinding and ssDUE binding, thereby supporting basal DnaB loading activity. This sub-complex is further subdivided into two; the DUE-distal DnaA sub-complex formed on the ATP-DnaA-preferential sites binds ssDUE. Notably, the DUE-flanking, DnaA box R1-DnaA sub-complex recruits DUE to the DUE-distal DnaA sub-complex in concert with a DNA-bending nucleoid protein IHF, thereby promoting DUE unwinding and binding of ssDUE. The right-half DAR-DnaA sub-complex stimulated DnaB loading, consistent with in vivo analyses. Similar features are seen in DUE unwinding of the hyperthermophile, Thermotoga maritima, indicating evolutional conservation of those mechanisms. PMID- 22053084 TI - SMART 7: recent updates to the protein domain annotation resource. AB - SMART (Simple Modular Architecture Research Tool) is an online resource (http://smart.embl.de/) for the identification and annotation of protein domains and the analysis of protein domain architectures. SMART version 7 contains manually curated models for 1009 protein domains, 200 more than in the previous version. The current release introduces several novel features and a streamlined user interface resulting in a faster and more comfortable workflow. The underlying protein databases were greatly expanded, resulting in a 2-fold increase in number of annotated domains and features. The database of completely sequenced genomes now includes 1133 species, compared to 630 in the previous release. Domain architecture analysis results can now be exported and visualized through the iTOL phylogenetic tree viewer. 'metaSMART' was introduced as a novel subresource dedicated to the exploration and analysis of domain architectures in various metagenomics data sets. An advanced full text search engine was implemented, covering the complete annotations for SMART and Pfam domains, as well as the complete set of protein descriptions, allowing users to quickly find relevant information. PMID- 22053083 TI - Developmental regulation of N-terminal H2B methylation in Drosophila melanogaster. AB - Histone post-translational modifications play an important role in regulating chromatin structure and gene expression in vivo. Extensive studies investigated the post-translational modifications of the core histones H3 and H4 or the linker histone H1. Much less is known on the regulation of H2A and H2B modifications. Here, we show that a major modification of H2B in Drosophila melanogaster is the methylation of the N-terminal proline, which increases during fly development. Experiments performed in cultured cells revealed higher levels of H2B methylation when cells are dense, regardless of their cell cycle distribution. We identified dNTMT (CG1675) as the enzyme responsible for H2B methylation. We also found that the level of N-terminal methylation is regulated by dART8, an arginine methyltransferase that physically interacts with dNTMT and asymmetrically methylates H3R2. Our results demonstrate the existence of a complex containing two methyltransferases enzymes, which negatively influence each other's activity. PMID- 22053085 TI - Conformational dynamics of the tetracycline-binding aptamer. AB - The conformational dynamics induced by ligand binding to the tetracycline-binding aptamer is monitored via stopped-flow fluorescence spectroscopy and time correlated single photon counting experiments. The fluorescence of the ligand is sensitive to changes within the tertiary structure of the aptamer during and after the binding process. In addition to the wild-type aptamer, the mutants A9G, A13U and A50U are examined, where bases important for regulation are changed to inhibit the aptamer's function. Our results suggest a very fast two-step mechanism for the binding of the ligand to the aptamer that can be interpreted as a binding step followed by a reorganization of the aptamer to accommodate the ligand. Binding to the two direct contact points A13 and A50 was found to occur in the first binding step. The exchange of the structurally important base A9 for guanine induces an enormous deceleration of the overall binding process, which is mainly rooted in an enhancement of the back reaction of the first binding step by several orders of magnitude. This indicates a significant loss of tertiary structure of the aptamer in the absence of the base A9, and underlines the importance of pre-organization on the overall binding process of the tetracycline binding aptamer. PMID- 22053086 TI - Comprehensive survey and geometric classification of base triples in RNA structures. AB - Base triples are recurrent clusters of three RNA nucleobases interacting edge-to edge by hydrogen bonding. We find that the central base in almost all triples forms base pairs with the other two bases of the triple, providing a natural way to geometrically classify base triples. Given 12 geometric base pair families defined by the Leontis-Westhof nomenclature, combinatoric enumeration predicts 108 potential geometric base triple families. We searched representative atomic resolution RNA 3D structures and found instances of 68 of the 108 predicted base triple families. Model building suggests that some of the remaining 40 families may be unlikely to form for steric reasons. We developed an on-line resource that provides exemplars of all base triples observed in the structure database and models for unobserved, predicted triples, grouped by triple family, as well as by three-base combination (http://rna.bgsu.edu/Triples). The classification helps to identify recurrent triple motifs that can substitute for each other while conserving RNA 3D structure, with applications in RNA 3D structure prediction and analysis of RNA sequence evolution. PMID- 22053087 TI - MimoDB 2.0: a mimotope database and beyond. AB - Mimotopes are peptides with affinities to given targets. They are readily obtained through biopanning against combinatorial peptide libraries constructed by phage display and other display technologies such as mRNA display, ribosome display, bacterial display and yeast display. Mimotopes have been used to infer the protein interaction sites and networks; they are also ideal candidates for developing new diagnostics, therapeutics and vaccines. However, such valuable peptides are not collected in the central data resources such as UniProt and NCBI GenPept due to their 'unnatural' short sequences. The MimoDB database is an information portal to biopanning results of random libraries. In version 2.0, it has 15,633 peptides collected from 849 papers and grouped into 1818 sets. Besides the core data on panning experiments and their results, broad background information on target, template, library and structure is included. An accompanied benchmark has also been compiled for bioinformaticians to develop and evaluate their new models, algorithms and programs. In addition, the MimoDB database provides tools for simple and advanced searches, structure visualization, BLAST and alignment view on the fly. The experimental biologists can easily use the database as a virtual control to exclude possible target unrelated peptides. The MimoDB database is freely available at http://immunet.cn/mimodb. PMID- 22053088 TI - An unstructured 5'-coding region of the prfA mRNA is required for efficient translation. AB - Expression of virulence factors in the human bacterial pathogen Listeria monocytogenes is almost exclusively regulated by the transcriptional activator PrfA. The translation of prfA is controlled by a thermosensor located in the 5' untranslated RNA (UTR), and is high at 37 degrees C and low at temperatures <30 degrees C. In order to develop a thermoregulated translational expression system, the 5'-UTR and different lengths of the prfA-coding sequences were placed in front of lacZ. When expressed in Escherichia coli, the beta-galactosidase expression was directly correlated to the length of the prfA-coding mRNA lying in front of lacZ. A similar effect was detected with gfp as a reporter gene in both L. monocytogenes and E. coli, emphasizing the requirement of the prfA-coding RNA for maximal expression. In vitro transcription/translation and mutational analysis suggests a role for the first 20 codons of the native prfA-mRNA for maximal expression. By toe-print and RNA-probing analysis, a flexible hairpin loop located immediately downstream of the start-codon was shown to be important for ribosomal binding. The present work determines the importance of an unstructured part of the 5'-coding region of the prfA-mRNA for efficient translation. PMID- 22053089 TI - InterEvol database: exploring the structure and evolution of protein complex interfaces. AB - Capturing how the structures of interacting partners evolved at their binding interfaces is a fundamental issue for understanding interactomes evolution. In that scope, the InterEvol database was designed for exploring 3D structures of homologous interfaces of protein complexes. For every chain forming a complex in the protein data bank (PDB), close and remote structural interologs were identified providing essential snapshots for studying interfaces evolution. The database provides tools to retrieve and visualize these structures. In addition, pre-computed multiple sequence alignments of most likely interologs retrieved from a wide range of species can be downloaded to enrich the analysis. The database can be queried either directly by pdb code or keyword but also from the sequence of one or two partners. Interologs multiple sequence alignments can also be recomputed online with tailored parameters using the InterEvolAlign facility. Last, an InterEvol PyMol plugin was developed to improve interactive exploration of structures versus sequence alignments at the interfaces of complexes. Based on a series of automatic methods to extract structural and sequence data, the database will be monthly updated. Structures coordinates and sequence alignments can be queried and downloaded from the InterEvol web interface at http://biodev.cea.fr/interevol/. PMID- 22053090 TI - The non-autonomous retrotransposon SVA is trans-mobilized by the human LINE-1 protein machinery. AB - SINE-VNTR-Alu (SVA) elements are non-autonomous, hominid-specific non-LTR retrotransposons and distinguished by their organization as composite mobile elements. They represent the evolutionarily youngest, currently active family of human non-LTR retrotransposons, and sporadically generate disease-causing insertions. Since preexisting, genomic SVA sequences are characterized by structural hallmarks of Long Interspersed Elements 1 (LINE-1, L1)-mediated retrotransposition, it has been hypothesized for several years that SVA elements are mobilized by the L1 protein machinery in trans. To test this hypothesis, we developed an SVA retrotransposition reporter assay in cell culture using three different human-specific SVA reporter elements. We demonstrate that SVA elements are mobilized in HeLa cells only in the presence of both L1-encoded proteins, ORF1p and ORF2p. SVA trans-mobilization rates exceeded pseudogene formation frequencies by 12- to 300-fold in HeLa-HA cells, indicating that SVA elements represent a preferred substrate for L1 proteins. Acquisition of an AluSp element increased the trans-mobilization frequency of the SVA reporter element by ~25 fold. Deletion of (CCCTCT)(n) repeats and Alu-like region of a canonical SVA reporter element caused significant attenuation of the SVA trans-mobilization rate. SVA de novo insertions were predominantly full-length, occurred preferentially in G+C-rich regions, and displayed all features of L1-mediated retrotransposition which are also observed in preexisting genomic SVA insertions. PMID- 22053091 TI - Cardiovascular risk management in chronic kidney disease in general practice (the AusHEART study). AB - BACKGROUND: Chronic kidney disease (CKD) is common and increasing in prevalence. Adverse outcomes of CKD can be prevented through early detection and treatment. There is limited data on the awareness of CKD and the quality of care offered to patients with CKD in the primary care setting. The objectives of this study were to assess the prevalence, general practitioner (GP) awareness and extent of current evidence-practice gaps in the management of CKD in Australian primary care. METHODS: The Australian Hypertension and Absolute Risk Study (AusHEART) was a nationally representative, cluster stratified, cross-sectional survey among 322 GPs. Each GP was asked to provide data for 15-20 consecutive patients (age >= 55 years) who presented between April and June, 2008. The main outcome measures were CKD prevalence based on proteinuria and decreased estimated glomerular filtration rate. Evidence-practice gaps in management of patients with CKD were identified. RESULTS: Among a total of 4966 patients with kidney function test data, 1845 (37%) had abnormal kidney function. Of the 1312 patients with abnormal kidney function known to the GP at the time of visit, only 235 were correctly identified as having CKD. GPs under-estimated cardiovascular (CV) risks in patients with CKD when compared with the prevailing guidelines at the time of survey and the recent national guidelines, particularly in later stages of CKD. Among CKD patients not prescribed blood pressure-lowering agents or lipid-lowering agents, treatment was indicated as per relevant guidelines in 51 and 46%, respectively. For CKD patients who were already prescribed blood pressure-lowering and lipid-lowering agents, 61 and 50%, respectively, did not meet the treatment targets recommended by the relevant guidelines. CONCLUSIONS: CKD is common, significantly under recognized and under-treated in primary care. Effort to increase awareness and provide opportunities for improved screening and assessment should improve the management and outcome of these patients at high risk of CV disease. PMID- 22053092 TI - Toll-like receptor 4 and MYD88-dependent signaling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium. AB - Infection of the bovine endometrium with Gram-negative bacteria commonly causes uterine disease. Toll-like receptor 4 (TLR4) on cells of the immune system bind Gram-negative bacterial lipopolysaccharide (LPS), stimulating the secretion of the proinflammatory cytokines interleukin 1B (IL1B) and IL6, and the chemokine IL8. Because the endometrium is the first barrier to infection of the uterus, the signaling cascade triggered by LPS and the subsequent expression of inflammatory mediators were investigated in endometrial epithelial and stromal cells, and the key pathways identified using short interfering RNA (siRNA) and biochemical inhibitors. Treatment of endometrial cells with ultrapure LPS stimulated an inflammatory response characterized by increased IL1B, IL6, and IL8 mRNA expression, and IL6 protein accumulation in epithelial cells, and by increased IL1B and IL8 mRNA expression, and IL6 and IL8 protein accumulation in stromal cells. Treatment of endometrial cells with LPS also induced the degradation of IKB and the nuclear translocation of NFKB, as well as rapid phosphorylation of mitogen-activated protein kinase 3/1 (MAPK3/1) and MAPK14. Knockdown of TLR4 or its signaling adaptor molecule, myeloid differentiation factor 88 (MYD88), using siRNA reduced the inflammatory response to LPS in epithelial and stromal cells. Biochemical inhibition of MAPK3/1, but not JNK or MAPK14, reduced LPS-induced IL1B, IL6, and IL8 expression in endometrial cells. In conclusion, epithelial and stromal cells have an intrinsic role in innate immune surveillance in the endometrium, and in the case of LPS this recognition occurs via TLR4- and MYD88 dependent cell signaling pathways. PMID- 22053093 TI - Leukemia inhibitory factor regulates differentiation of trophoblastlike BeWo cells through the activation of JAK/STAT and MAPK3/1 MAP kinase-signaling pathways. AB - It is well established that syncytium formation involves the fusion of mononucleated trophoblasts into a multinucleated structure and the secretion of hormonal factors, such as human chorionic gonadotropin (hCG). These morphological and biochemical changes are regulated by a plethora of ligands, which upon binding to specific receptors trigger the activation of many signaling pathways, such as janus kinase/signal transducer and activator of transcription (JAK/STAT) and the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinases 1 and 2 (MAPK3/1). We used the forskolin-induced syncytialization of trophoblastlike BeWo cells to characterize at the cellular level the effect mediated by leukemia inhibitory factor (LIF) on trophoblast differentiation and to describe its action at the molecular level. Forskolin induces both hCG secretion and BeWo cell syncytial fusion. Although LIF had no effect on the undifferentiated state of the cells, the cytokine generated a strong reduction in forskolin-induced hCG release. In contrast to its effect on hCG secretion, LIF exerts a synergistic effect toward forskolin-induced fusion. LIF reduced hormonal production through a STAT1- and STAT3-dependent mechanism, whereas MAPK3/1 was not involved in this process. However, both types of signaling molecules were required to mediate the action of LIF in forskolin-induced cell fusion. These data provide novel insights into the regulation of trophoblast cell differentiation by LIF and describe for the first time the molecular mechanism underlying the effect of the cytokine. PMID- 22053094 TI - The interaction between photoperiod and nutrition and its effects on seasonal rhythms of reproduction in the ewe. AB - In sheep, the seasonal patterns of reproductive activity are driven primarily by the annual photoperiodic cycle, but can also respond to other environmental factors, such as nutrition, yet little is known about the mechanisms underlying this interaction. This study was designed to define the interaction between photoperiodic and nutritional cues on seasonal patterns of ovarian activity, and to determine if there is a central interaction between these cues. Groups of Ile de-France ewes were maintained in two nutritional states (restricted and well fed) under a simulated annual photoperiod of 8-16 h of light per day over two breeding seasons. At the end of the first breeding season, half of the animals of each group were ovariectomized (OVX) and fitted subcutaneously with estradiol implants. Low nutritional status shortened the season of ovarian activity, determined from the pattern of progesterone concentrations, by modifying the timing of seasonal transitions between periods of ovarian activity and anestrus. The same results were observed for the seasonal rhythm of neuroendocrine activity, assessed in the OVX ewes, from the pattern of luteinizing hormone concentrations. These results were then confirmed for neuroendocrine activity induced by a photoperiodic treatment. We conclude that nutrition centrally modulates the interpretation of photoperiod to affect seasonal reproductive transitions. The mechanisms of this interaction are discussed in the paper. PMID- 22053095 TI - TIMP1 contributes to ovarian anomalies in both an MMP-dependent and -independent manner in a rat model. AB - Ovulatory dysfunction occurs in women with endometriosis, yet the mechanisms are unknown. We have shown that endometriotic lesions synthesize and secrete tissue inhibitor of metalloproteinase (TIMP) 1 into the peritoneal cavity in humans and a rat model of endometriosis, where excess TIMP1 localizes in the ovarian theca in endometriosis and modulating peritoneal TIMP1 alters ovarian dynamics. Here, we evaluated whether mechanisms whereby excessive peritoneal fluid TIMP1 negatively impacts ovarian function are matrix metalloproteinase (MMP)-dependent and/or MMP-independent actions. Rats were treated with a mutated TIMP1 without MMP inhibitory function (Ala-TIMP1), wild-type TIMP1 (rTIMP1), or PBS. Rats treated with Ala-TIMP1 or rTIMP1 had fewer antral follicles, fewer new corpora lutea, and the presence of luteinized unruptured follicle syndrome compared with PBS rats. Ala-TIMP1 and rTIMP1 differentially caused downstream changes in gene expression and protein localization related to ovulation, as measured by whole genome microarray with quantitative real-time PCR validation and immunohistochemistry. More vascular endothelial growth factor and FN were expressed and localized in ovaries of Ala-TIMP1-treated rats compared to rTIMP1- and PBS-treated rats inferring MMP-independent functions. Less caspase 3 localized in ovaries of rTIMP1 compared with the other two groups, and was thus dependent on MMP action. Furthermore, after coimmunoprecipitation, more CD63 was bound to TIMP1 in ovaries of rats treated with Ala-TIMP1 than in rTIMP1-treated rats, providing evidence for another MMP-independent mechanism of ovulatory dysfunction. We predict that MMP-dependent and MMP-independent events are involved in improper fortification of the follicular wall through multiple mechanisms, such as apoptosis inhibition, extracellular matrix components and angiogenesis. Collectively, excessive peritoneal TIMP1 causes changes in ovarian dynamics, both dependently and independently of MMP inhibition. PMID- 22053096 TI - Ontogeny of aquaporins in human fetal membranes. AB - It has been proposed that four members of the aquaporin family (AQPs 1, 3, 8, and 9) are involved in the control of amniotic fluid (AF) homeostasis, as illustrated by their differential expression patterns in normal and pathological human term fetal membranes. However, there are no data available to date on their ontogeny throughout pregnancy. Our objective was to determine spatiotemporal expression profiles of the mRNA and proteins of all 13 members of this transmembrane channel family. For this purpose, we used healthy fetal membranes from the first, second, and third trimesters of pregnancy. Total mRNA and proteins were extracted from total membranes and from separated amnion and chorion. Quantitative PCR, Western blot, and immunohistochemistry experiments were carried out to determine the presence of AQPs and to quantify their spatiotemporal expression patterns throughout pregnancy. The WISH cell line was tested to propose a cellular model for the role of AQPs in the amnion compartment. AQP11 expression was established in amniotic membranes at term. Aquaporins 1, 3, 8, 9, and 11 mRNA and proteins were present in amnion and chorion throughout human gestation. Each AQP has a time-specific expression pattern, with AQP1 presenting the highest variation in terms of mRNA and protein levels. The WISH cell line also expressed the same five AQPs. Taken together, these results indicate that AQPs are expressed and potentially involved in the regulation of AF homeostasis throughout pregnancy. This also clearly supports the hypothesis that abnormal expression could occur at any time during pregnancy, ultimately leading to obstetrical pathologies such as polyhydramnios or oligohydramnios. PMID- 22053097 TI - Effect of aging on superovulation efficiency, aneuploidy rates, and sister chromatid cohesion in mice aged up to 15 months. AB - Human eggs are highly aneuploid, with female age being the only known risk factor. Here this aging phenomenon was further studied in Swiss CD1 mice aged between 1 and 15 mo. The mean number of eggs +/- SEM recovered from mice following superovulation peaked at 22.5 +/- 3.8 eggs/oviduct in 3-mo-old females, decreasing markedly between 6 and 9 mo old, and was only 2.1 +/- 0.2 eggs/oviduct by 15 mo. Measurement of aneuploidy in these eggs revealed a low rate, ~3-4%, in mice aged 1 and 3 mo, rising to 12.5% by 9 mo old and to 37.5% at 12 mo. Fifteen month-old mice had the highest rate of aneuploidy, peaking at 60%. The in situ chromosome counting technique used here allowed us to measure with accuracy the distance between the kinetochores in the sister chromatids of the eggs analyzed for aneuploidy. We observed that this distance increased in eggs from older females, from 0.38 +/- 0.01 MUm at 1 mo old to 0.82 +/- 0.03 MUm by 15 mo. Furthermore, in 3- to 12-mo-old females, aneuploid eggs had significantly larger interkinetochore distances than euploid eggs from the same age, and measurements were similar to eggs from the oldest mice. However, the association between aneuploidy and interkinetochore distance was not observed at the oldest, 15-mo age, despite such measurements being maximal. We conclude that in aging CD1 mice, a reduction in the ovulated egg number precedes a rise in aneuploidy and, furthermore, except at very advanced ages, increased interkinetochore distance is associated with aneuploidy. PMID- 22053099 TI - A checklist for cerebral aneurysm embolization complications. AB - Complications during cerebral aneurysm embolization continue to occur even at high volume experienced centers. Such situations are unexpected, complex and can have devastating consequences. Individual anecdotal experience offers limited guidance. This literature review of the two most serious neuroendovascular procedural complications-namely, aneurysm perforation and thromboemboli-aims to propose a role based checklist. Having a premeditated plan helps team members remain calm and function more effectively when a procedural complication occurs, with the ultimate goal of minimizing patient harm. PMID- 22053098 TI - Cold-shock-domain protein A (CSDA) contributes posttranscriptionally to gonadotropin-releasing hormone-regulated expression of Egr1 and indirectly to Lhb. AB - Gonadotropin-releasing hormone (GnRH), a hypothalamic neurohormone, regulates transcription of Lhb in gonadotrophs indirectly through transient induction and accumulation of EGR1, a zinc finger transcription factor. AlphaT3 and LbetaT2 cell lines model gonadotrophs at two distinct stages of development, prenatal and postnatal expression of Lhb. Although GnRH induces EGR1 in both cell lines, the levels of the DNA-binding protein are lower and disappear more quickly in alphaT3 than in LbetaT2 cells. Herein we show that overexpression of Egr1 in alphaT3 cells rescues activity of a transfected LHB promoter-reporter, suggesting that its transcription is dependent on EGR1 crossing a critical concentration threshold. We also show that Csda, a gene that encodes an RNA-binding protein and is a member of the cold-shock-domain (CSD) family, is expressed at higher levels in LbetaT2 compared to alphaT3 cells. Transient expression studies indicate that at least one Csd element, residing in the 3' untranslated region of Egr1 mRNA, increases activity of a chimeric pGL3 luciferase reporter vector in LbetaT2 cells. Additional experiments indicate that CSDA physically interacts with Egr1 mRNA. Furthermore, siRNA-mediated reduction of endogenous Csda mRNA attenuates GnRH regulation of a transiently transfected LHB reporter vector. Taken together, these studies suggest that CSDA contributes posttranscriptionally to GnRH regulated expression of Egr1, thereby enabling the transcription factor to cross a critical concentration threshold necessary for maximal accumulation of Lhb mRNA in response to the neurohormone. PMID- 22053100 TI - A randomised placebo-controlled trial of topical steroid in presumed viral conjunctivitis. PMID- 22053102 TI - Oral rifampin utilisation for the treatment of chronic multifocal central serous retinopathy. AB - Chronic central serous retinopathy (CSR) is characterised by frequent exacerbations and a poor visual prognosis. Very few therapies exist for chronic CSR, and the existing therapies are often ineffective. Thus, novel therapies to combat this frustrating disorder are needed. Presented here is a case detailing a patient with chronic CSR with persistent subfoveal fluid of 2 years' duration that completely resolved with 1 month of oral rifampin therapy. As a cytochrome P450, 3A4 inducer, rifampin is thought to favourably alter the metabolism of endogenous steroids, thereby leading to an improvement in CSR manifestations. PMID- 22053101 TI - Intra-arterial chemotherapy for retinoblastoma in eyes with vitreous and/or subretinal seeding: 2-year results. AB - BACKGROUND/AIMS: To review the effectiveness of intra-arterial chemotherapy for advanced intra-ocular retinoblastoma with vitreous and/or subretinal seeds in naive (untreated) and previously treated eyes. METHODS: Retrospective study, approved by the institutional review board, of 76 eyes of 67 patients with retinoblastoma with subretinal and/or vitreous seeding treated with intra arterial chemotherapy at Memorial Sloan-Kettering Cancer Center between May 2006 and August 2010. RESULTS: Despite advanced intraocular disease with seeding, the majority (56/76) of eyes were saved; 20/76 eyes were enucleated. Among treatment naive eyes, the 2-year probability of ocular salvage was 83% (95% CI 27% to 97%) for eyes with subretinal seeding only, 64% (95% CI 24% to 87%) for eyes with vitreous seeding only, and 80% (95% CI 40% to 95%) for eyes with both. Among eyes that received previous treatment and had progressed, the 2-year probability of ocular salvage was 50% (95% CI 15% to 78%) for eyes with only subretinal seeding, 76% (95% CI 48% to 91%) for eyes with vitreous seeding only, and 54% (95% CI 20% to 79%) for eyes with both. Nine of 29 naive eyes (31%) were cured with intra arterial (super-selective ophthalmic artery infusion of chemotherapy) chemotherapy alone. CONCLUSION: Unlike radiation or systemic chemotherapy, intra arterial chemotherapy can usually prevent the need for enucleation in naive eyes with advanced intraocular retinoblastoma with seeding-especially if the seeding is subretinal. Treatment appears to be less effective in previously treated eyes when subretinal seeding is present (50% at 2 years), but may be more effective in eyes that failed to respond to previous systemic chemotherapy and have only vitreous seeding. PMID- 22053103 TI - Restrictive anorexia nervosa: a silent enemy for the eyes and vision. PMID- 22053104 TI - Comparison of stem cell sources in the severity of dry eye after allogeneic haematopoietic stem cell transplantation. AB - AIMS: To compare the incidence and severity of dry eye (DE) after allogeneic haematopoietic stem cell transplantation (HSCT) according to the stem cell source. The authors specifically focused on patients who received bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT) and cord blood transplantation (CBT). METHODS: Ninety-nine HSCT recipients who were prospectively followed-up for at least 100 days at Keio University Hospital were recruited. Ophthalmological examinations included evaluation of ocular surface findings and tear dynamics. The data on systemic graft-versus-host disease were collected by chart review. RESULTS: Of the 99 patients (BMT, 67; PBSCT, 18; CBT, 14), 42 developed DE or showed worsened pre-existing DE after HSCT; 31 (46.3%) BMT group; 8 (44.0%) PBSCT group; and 3 (21.4%) CBT group (p=0.78). The median onset time of DE tended to be later in the PBSCT group (474 days, range 95-1559) than in the BMT (287 days, range 67-1216) or CBT (168 days, range 33-481) group, but the difference was not significant (p=0.23). However, the proportion of patients with severe DE was significantly higher in the PBSCT group (N=7, 87.5%) than in the BMT (N=12, 38.7%) or CBT (N=1, 33.3%) group (p=0.04) and CBT showed the lowest among all three stem cell sources. CONCLUSION: The data in this study suggested that the severity and onset time of DE were affected by the stem cell source. Close attention must be paid to the development of late-onset severe DE in PBSCT recipients. PMID- 22053105 TI - mTORC1 and mTORC2 differentially regulate homeostasis of neoplastic and non neoplastic human mast cells. AB - Increased mast cell burden is observed in the inflamed tissues and affected organs and tissues of patients with mast cell proliferative disorders. However, normal mast cells participate in host defense, so approaches to preferentially target clonally expanding mast cells are needed. We found that mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) are up-regulated in neoplastic and developing immature mast cells compared with their terminally differentiated counterparts. Elevated mTOR mRNA was also observed in bone marrow mononuclear cells of patients exhibiting mast-cell hyperplasia. Selective inhibition of mTORC1 and mTORC2 through genetic and pharmacologic manipulation revealed that, whereas mTORC1 may contribute to mast-cell survival, mTORC2 was only critical for homeostasis of neoplastic and dividing immature mast cells. The cytostatic effect of mTORC2 down-regulation in proliferating mast cells was determined to be via inhibition of cell-cycle progression. Because mTORC2 was observed to play little role in the homeostasis of differentiated, nonproliferating, mature mast cells, these data provide a rationale for adopting a targeted approaching selectively inhibiting mTORC2 to effectively reduce the proliferation of mast cells associated with inflammation and disorders of mast cell proliferation while leaving normal differentiated mast cells largely unaffected. PMID- 22053106 TI - Inhibition of PPARgamma in myeloid-lineage cells induces systemic inflammation, immunosuppression, and tumorigenesis. AB - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is an anti inflammatory molecule. To study its biologic function in myeloid cells, dominant negative PPARgamma (dnPPARgamma) was overexpressed in a myeloid-specific bitransgenic mouse model. In this bitransgenic system, overexpression of the dnPPARgamma-Flag fusion protein in myeloid-lineage cells abnormally elevated frequencies and total numbers of IL-7Ralpha(-)Lin(-)c-Kit(+)Sca-1(-), Lin( )/Scal(+)/c-Kit(+), common myeloid, and granulocyte-monocyte progenitor populations in the BM. dnPPARgamma overexpression led to up-regulation of IL 1beta, IL-6, and TNFalpha in the blood plasma. As a result, CD11b(+)Ly6G(+) cells were systemically increased in association with activation of Stat3, NF-kappaB, Erk1/2, and p38 molecules. Myeloid-derived suppressor cells (MDSCs) inhibited the proliferation and lymphokine production of wild-type CD4+ T cells in vitro. CD4+ T cells from doxycycline-treated bitransgenic mice displayed reduced proliferation and lymphokine release. Both CD4+ and CD8+ T-cell populations were decreased in doxycycline-treated bitransgenic mice. Multiple forms of carcinoma and sarcoma in the lung, liver, spleen, and lymph nodes were observed in doxycycline-treated bitransgenic mice. BM transplantation revealed that a myeloid autonomous defect was responsible for MDSC expansion, immunosuppression, and tumorigenesis in these mice. These studies suggest that anti-inflammatory PPARgamma in myeloid-lineage cells plays a key role in controlling pro inflammatory cytokine synthesis, MDSC expansion, immunosuppression, and the development of cancer. PMID- 22053107 TI - Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice. AB - Extracellular ATP and UTP nucleotides increase the proliferation and engraftment potential of normal human hematopoietic stem cells via the engagement of purinergic receptors (P2Rs). In the present study, we show that ATP and UTP have strikingly opposite effects on human acute myeloblastic leukemia (AML) cells. Leukemic cells express P2Rs. ATP-stimulated leukemic cells, but not normal CD34+ cells, undergo down-regulation of genes involved in cell proliferation and migration, whereas cell-cycle inhibitors are up-regulated. Functionally, ATP induced the inhibition of proliferation and accumulation of AML cells, but not of normal cells, in the G0 phase of the cell cycle. Exposure to ATP or UTP inhibited AML-cell migration in vitro. In vivo, xenotransplantation experiments demonstrated that the homing and engraftment capacity of AML blasts and CD34+CD38 cells to immunodeficient mice BM was significantly inhibited by pretreatment with nucleotides. P2R-expression analysis and pharmacologic profiling suggested that the inhibition of proliferation by ATP was mediated by the down-regulation of the P2X7R, which is up-regulated on untreated blasts, whereas the inhibition of chemotaxis was mainly mediated via P2Y2R and P2Y4R subtypes. We conclude that, unlike normal cells, P2R signaling inhibits leukemic cells and therefore its pharmacologic modulation may represent a novel therapeutic strategy. PMID- 22053108 TI - Inactivation of polycomb repressive complex 2 components in myeloproliferative and myelodysplastic/myeloproliferative neoplasms. AB - The polycomb repressive complex 2 (PRC2) is a highly conserved histone H3 lysine 27 methyltransferase that regulates the expression of developmental genes. Inactivating mutations of the catalytic component of PRC2, EZH2, are seen in myeloid disorders. We reasoned that the other 2 core PRC2 components, SUZ12 and EED, may also be mutational targets in these diseases, as well as associated factors such as JARID2. SUZ12 mutations were identified in 1 of 2 patients with myelodysplastic syndrome/myeloproliferative neoplasms with 17q acquired uniparental disomy and in 2 of 2 myelofibrosis cases with focal 17q11 deletions. All 3 were missense mutations affecting the highly conserved VEFS domain. Analysis of a further 146 myelodysplastic syndrome/myeloproliferative neoplasm patients revealed an additional VEFS domain mutant, yielding a total mutation frequency of 1.4% (2 of 148). We did not find mutations of JARID2 or EED in association with acquired uniparental disomy for chromosome 6p or 11q, respectively; however, screening unselected cases identified missense mutations in EED (1 of 148; 1%) and JARID2 (3 of 148; 2%). All 3 SUZ12 mutations tested and the EED mutation reduced PRC2 histone methyltransferase activity in vitro, demonstrating that PRC2 function may be compromised in myeloid disorders by mutation of distinct genes. PMID- 22053110 TI - Microfabricated optofluidic ring resonator structures. AB - We describe the fabrication and preliminary optical characterization of rugged, Si-micromachined optofluidic ring resonator (MUOFRR) structures consisting of thin-walled SiO(x) cylinders with expanded midsections designed to enhance the three-dimensional confinement of whispering gallery modes (WGMs). These MUOFRR structures were grown thermally at wafer scale on the interior of Si molds defined by deep-reactive-ion etching and pre-treated to reduce surface roughness. Devices 85-MUm tall with 2-MUm thick walls and inner diameters ranging from 50 to 200 MUm supported pure-mode WGMs with Q-factors >10(4) near 985 nm. Advantages for eventual vapor detection in gas chromatographic microsystems are highlighted. PMID- 22053111 TI - Insight into unusual impurity absorbability of GeO(2) in GeO(2)/Ge stacks. AB - Adsorbed species and its diffusion behaviors in GeO(2)/Ge stacks, which are future alternative metal-oxide-semiconductor (MOS) materials, have been investigated using various physical analyses. We clarified that GeO(2) rapidly absorbs moisture in air just after its exposure. After the absorbed moisture in GeO(2) reaches a certain limit, the GeO(2) starts to absorb some organic molecules, which is accompanied by a structural change in GeO(2) to form a partial carbonate or hydroxide. We also found that the hydrogen distribution in GeO(2) shows intrinsic characteristics, indicative of different diffusion behaviors at the surface and at the GeO(2)/Ge interface. Because the impurity absorbability of GeO(2) has a great influence on the electrical properties in Ge MOS devices, these results provide valuable information in realizing high quality GeO(2)/Ge stacks for the actual use of Ge-MOS technologies. PMID- 22053109 TI - Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. AB - Although activity that induced tumor regression was observed and termed tumor necrosis factor (TNF) as early as the 1960s, the true identity of TNF was not clear until 1984, when Aggarwal and coworkers reported, for the first time, the isolation of 2 cytotoxic factors: one, derived from macrophages (molecular mass 17 kDa), was named TNF, and the second, derived from lymphocytes (20 kDa), was named lymphotoxin. Because the 2 cytotoxic factors exhibited 50% amino acid sequence homology and bound to the same receptor, they came to be called TNF alpha and TNF-beta. Identification of the protein sequences led to cloning of their cDNA. Based on sequence homology to TNF-alpha, now a total of 19 members of the TNF superfamily have been identified, along with 29 interacting receptors, and several molecules that interact with the cytoplasmic domain of these receptors. The roles of the TNF superfamily in inflammation, apoptosis, proliferation, invasion, angiogenesis, metastasis, and morphogenesis have been documented. Their roles in immunologic, cardiovascular, neurologic, pulmonary, and metabolic diseases are becoming apparent. TNF superfamily members are active targets for drug development, as indicated by the recent approval and expanding market of TNF blockers used to treat rheumatoid arthritis, psoriasis, Crohns disease, and osteoporosis, with a total market of more than US $20 billion. As we learn more about this family, more therapeutics will probably emerge. In this review, we summarize the initial discovery of TNF-alpha, and the insights gained regarding the roles of this molecule and its related family members in normal physiology and disease. PMID- 22053112 TI - DOES HAVING A DYSFUNCTIONAL PERSONALITY HURT YOUR CAREER? AXIS II PERSONALITY DISORDERS AND LABOR MARKET OUTCOMES. AB - Despite recent interest in how psychiatric disorders affect work outcomes, little is known about the role of personality disorders (PDs), which are poorly understood yet prevalent (15%) and impairing. We used nationally representative data for 12,457 men and 16,061 women to examine associations of PDs with any employment, full-time employment, chronic unemployment, being fired or laid off, and having trouble with a boss or co-worker. Antisocial, paranoid, and obsessive compulsive PDs demonstrated the broadest patterns of associations with adverse outcomes. Findings suggest that PDs may have implications for the productivity of co-workers as well as that of the disordered employees themselves. PMID- 22053113 TI - Enthalpies of mixing of liquid systems for lead free soldering: Al-Cu-Sn system. AB - The present work refers to high-temperature drop calorimetric measurements on liquid Al-Cu, Al-Sn, and Al-Cu-Sn alloys. The binary systems have been investigated at 973 K, up to 40 at.% Cu in case of Al-Cu, and over the entire concentrational range in case of Al-Sn. Measurements in the ternary Al-Cu-Sn system were performed along the following cross-sections: x(Al)/x(Cu) = 1:1, x(Al)/x(Sn) = 1:1, x(Cu)/x(Sn) = 7:3, x(Cu)/x(Sn) = 1:1, and x(Cu)/x(Sn) = 3:7 at 1273 K. Experimental data were used to find ternary interaction parameters by applying the Redlich-Kister-Muggianu model for substitutional solutions, and a full set of parameters describing the concentration dependence of the enthalpy of mixing was derived. From these, the isoenthalpy curves were constructed for 1273 K. The ternary system shows an exothermic enthalpy minimum of approx. -18,000 J/mol in the Al-Cu binary and a maximum of approx. 4000 J/mol in the Al-Sn binary system. The Al-Cu-Sn system is characterized by considerable repulsive ternary interactions as shown by the positive ternary interaction parameters. PMID- 22053114 TI - Self-seeded, position-controlled InAs nanowire growth on Si: A growth parameter study. AB - In this work, the nucleation and growth of InAs nanowires on patterned SiO(2)/Si(111) substrates is studied. It is found that the nanowire yield is strongly dependent on the size of the etched holes in the SiO(2), where openings smaller than 180 nm lead to a substantial decrease in nucleation yield, while openings larger than ~500nm promote nucleation of crystallites rather than nanowires. We propose that this is a result of indium particle formation prior to nanowire growth, where the size of the indium particles, under constant growth parameters, is strongly influenced by the size of the openings in the SiO(2) film. Nanowires overgrowing the etched holes, eventually leading to a merging of neighboring nanowires, shed light into the growth mechanism. PMID- 22053115 TI - Opting Out and Buying Out: Wives' Earnings and Housework Time. AB - It has been proposed that the negative association between wives' earnings and their time in housework is due to greater outsourcing of household labor by households with high-earning wives, but this hypothesis has not been tested directly. In a sample of dual-earner married couples in the Consumption and Activities Mail Survey of the Health and Retirement Study (N = 796), use of market substitutes for women's housework was found to be only weakly associated with wives' time cooking and cleaning. Furthermore, expenditures on market substitutes explain less than 15% of the earnings-housework time relationship. This suggests that use of market substitutes plays a smaller role in explaining variation in wives' time in household labor than has previously been hypothesized. PMID- 22053116 TI - L-Proline Functionalized Polymers Prepared by RAFT Polymerization and Their Assemblies as Supported Organocatalysts. AB - We have prepared a range of well-defined copolymers of styrene and L-proline functionalized styrene (5-11 kDa) using reversible addition-fragmentation chain transfer (RAFT) polymerization techniques and explored their use in supported catalysis. Upon deprotection of the L-proline functionalities, the solution self assembly of these copolymers was investigated in mixed solvent systems. The resulting assemblies were characterized by dynamic light scattering, transmission electron microscopy (on graphene oxide substrates, along with cryo-TEM and tomography), and scanning electron microscopy. The application of these functional assemblies as supported catalysts for the aldol condensation reaction was explored using cyclohexanone and 4-nitrobenzaldehyde. The rate and selectivity of solution catalysis in our self-assembled system were comparable to those of L-proline, and a significant advantage of our system was that the polymer support could be utilized at lower catalyst loadings with comparable activity and also could be recycled a number of times while maintaining activity and selectivity. PMID- 22053117 TI - A TAXONOMIC REVISION OF GOUANIA (RHAMNACEAE) IN MADAGASCAR AND THE OTHER ISLANDS OF THE WESTERN INDIAN OCEAN (THE COMORO AND MASCARENE ISLANDS, AND THE SEYCHELLES). AB - A taxonomic revision of the genus Gouania Jacq. (Rhamnaceae) is presented for Madagascar and the other western Indian Ocean islands. Seventeen species are recognized, of which nine are described and published as new (all endemic to Madagascar): G. ambrensis Buerki, Phillipson & Callm., G. callmanderi Buerki, G. cupreifolia Buerki, Phillipson & Callm., G. cupuliflora Buerki, Phillipson & Callm., G. gautieri Buerki, Phillipson & Callm., G. perrieri Buerki, Phillipson & Callm., G. phillipsonii Buerki, G. taolagnarensis Buerki, Phillipson & Callm., and G. zebrifolia Buerki, Phillipson & Callm. Sixteen species occur in Madagascar, of which 13 are endemic and three are common to Madagascar and one or more of the smaller Indian Ocean islands. The latter include G. laxiflora Tul., a species which is also present on mainland Africa. One species, G. mauritiana Lam., is endemic to Reunion Island. We recognize two subspecies within G. scandens (Gaertn.) R. B. Drumm.: G. scandens subsp. scandens and G. scandens subsp. glandulosa (Boivin ex Tul.) Buerki, Phillipson & Callm., the latter transferred from G. glandulosa Boivin ex Tul. Past confusion about the identity of this species is discussed. Five names are lectotypified: G. aphrodes Tul., G. glandulosa [= G. scandens subsp. glandulosa], G. laxiflora, G. lineata Tul., and G. tiliifolia Lam. Both lectotype and epitype are designated for G. mauritiana. Conservation assessments are provided for all species within their primary areas of occurrence. PMID- 22053118 TI - Resonant charge transfer in low-energy ion scattering: Information depth in the reionization regime. AB - Time-Of-Flight Low-energy ion scattering (TOF-LEIS) experiments were performed for He(+) ions scattered from Cu(100) and Cu(0.5)Au(0.5)(100). Probabilities for resonant neutralization and reionization in close collisions were deduced in a wide energy range. To learn about the information depth in LEIS, in a next step ion spectra were analyzed for polycrystalline Cu samples. The relative yield of backscattered projectiles, which have undergone distinct charge exchange processes, was calculated. Results indicate a strong contribution to the ion yield that origins from particles reionized in a close collision in deeper layers when experiments are performed at energies where reionization is prominent. The surface sensitivity of the ion signal at different energies is quantified. Based on these results, the total ion spectrum was quantitatively modelled by two consistent, but different approaches. PMID- 22053119 TI - First total synthesis of (+)-Vedelianin, a potent antiproliferative agent. AB - The total synthesis of (+)-vedelianin has been accomplished in 18 steps from vanillin. Preparation of a key intermediate in nonracemic form through a Shi epoxidation has allowed determination of the absolute stereochemistry of the natural product as the (2S, 3R, 4aR, 9aR)-isomer. PMID- 22053120 TI - The physical oceanography of upwelling systems and the development of harmful algal blooms. AB - The upwelling systems of the eastern boundaries of the world's oceans are susceptible to harmful algal blooms (HABs) because they are highly productive, nutrient-rich environments, prone to high-biomass blooms. This review identifies those aspects of the physical environment important in the development of HABs in upwelling systems through description and comparison of bloom events in the Benguela, California and Iberia systems. HAB development is dictated by the influence of wind stress on the surface boundary layer through a combination of its influence on surface mixed-layer characteristics and shelf circulation patterns. The timing of HABs is controlled by windstress fluctuations and buoyancy inputs at the seasonal, event and interannual scales. Within this temporal framework, various mesoscale features that interrupt typical upwelling circulation patterns, determine the spatial distribution of HABs. The inner shelf in particular provides a mosaic of shifting habitats, some of which favour HABs. Changes in coastline configuration and orientation, and bottom topography are important in determining the distribution of HABs through their influence on water stratification and retention. A spectrum of coastline configurations, including headlands, capes, peninsulas, Rias, bays and estuaries, representing systems of increasing isolation from the open coast and consequent increasing retention times, are assessed in terms of their vulnerability to HABs. PMID- 22053121 TI - Counteracting 'Not in My Backyard': The Positive Effects of Greater Occupancy within Mutual-help Recovery Homes. AB - Group homes sometimes face significant neighborhood opposition, and municipalities frequently use maximum occupancy laws to close down these homes. This study examined how the number of residents in Oxford House recovery homes impacted residents' outcomes. Larger homes (i.e., 8 or more residents) may reduce the cost per person and offer more opportunities to exchange positive social support, thus, it was predicted that larger Oxford Houses would exhibit improved outcomes compared to smaller homes. Regression analyses using data from 643 residents from 154 U.S. Oxford Houses indicated that larger House size predicted less criminal and aggressive behavior; additionally, length of abstinence was a partial mediator in these relationships. These findings have been used in court cases to argue against closing down larger Oxford Houses. 125 words. PMID- 22053122 TI - Dropout from interim methadone and subsequent comprehensive methadone maintenance. AB - BACKGROUND: Methadone maintenance in the U.S. is delivered primarily through specialized clinics that provide psychosocial services together with medication. Interim methadone (IM) is an evidence-based approach to increase access by providing methadone without counseling for individuals waiting for admission to comprehensive treatment. Little is known about the role of patient characteristics in predicting outcomes in the IM service pathway (IM with comprehensive methadone treatment following IM). METHODS: This study examined the relationship between patient motivation and dropout among patients in the IM service pathway (n=183). Participants were assessed with the Addiction Severity Index, the Texas Christian University Motivation Scales, and study-specific instruments at baseline, 4 month follow-up or admission to comprehensive treatment (whichever occurred first), and 6 months thereafter. Multinomial logistic regression was used for the analysis, controlling for demographics, route of administration, cocaine use, criminal justice history, and treatment history. RESULTS: Of the total sample, 62% were retained throughout the IM service pathway, 20% left IM, and 18% left subsequent comprehensive treatment. Motivation did not predict dropout from either IM or comprehensive treatment following IM. Unexpectedly, neither did any of the other explanatory variables included in the model. CONCLUSIONS: Most patients remained in the IM service pathway. The patient characteristics examined are not associated with discontinuation of IM or subsequent comprehensive methadone treatment. SCIENTIFIC SIGNIFICANCE: The findings that most patients were retained in the IM service pathway, and that no subgroup experienced higher probability of dropout, bolster the public health potential of IM as a service strategy. PMID- 22053123 TI - Adaptive Confidence Intervals for the Test Error in Classification. AB - The estimated test error of a learned classifier is the most commonly reported measure of classifier performance. However, constructing a high quality point estimator of the test error has proved to be very difficult. Furthermore, common interval estimators (e.g. confidence intervals) are based on the point estimator of the test error and thus inherit all the difficulties associated with the point estimation problem. As a result, these confidence intervals do not reliably deliver nominal coverage. In contrast we directly construct the confidence interval by use of smooth data-dependent upper and lower bounds on the test error. We prove that for linear classifiers, the proposed confidence interval automatically adapts to the non-smoothness of the test error, is consistent under fixed and local alternatives, and does not require that the Bayes classifier be linear. Moreover, the method provides nominal coverage on a suite of test problems using a range of classification algorithms and sample sizes. PMID- 22053124 TI - Correlations of cave levels, stream terraces and planation surfaces along the River Mur-Timing of landscape evolution along the eastern margin of the Alps. AB - The transition zone of the Eastern Alps to the Pannonian Basin provides one of the best sources of information on landscape evolution of the Eastern Alpine mountain range. The region was non-glaciated during the entire Pleistocene. Thus, direct influence of glacial carving as a landscape forming process can be excluded and relics of landforms are preserved that date back to at least the Late Neogene. In this study, we provide a correlation between various planation surfaces across the orogen-basin transition. In particular, we use stream terraces, planation surfaces and cave levels that cover a vertical spread of some 700 m. Our correlation is used to show that both sides of the transition zone uplifted together starting at least about 5 Ma ago. For our correlation we use recently published terrestrial cosmogenic nuclide (TCN) burial ages from cave sediments, new optically stimulated luminescence (OSL) ages of a stream terrace and U-Th ages from speleothems. Minimum age constraints of cave levels from burial ages of cave sediments covering the last ~ 4 Ma are used to place age constraints on surface features by parallelizing cave levels with planation surfaces. The OSL results for the top section of the type locality of the Helfbrunn terrace suggest an Early Wurm development (80.5 +/- 3.7 to 68.7 +/- 4.0 ka). The terrace origin as a penultimate gravel deposit (in classical Alpine terminology Riss) is therefore questioned. U-series speleothem ages from caves nearby indicate formation during Marine Isotope Stages (MIS) 5c and 5a which are both interstadial warm periods. As OSL ages from the terrace also show a time of deposition during MIS 5a ending at the MIS 5/4 transition, this supports the idea of temperate climatic conditions at the time of deposition. In general, tectonic activity is interpreted to be the main driving force for the formation and evolution of these landforms, whilst climate change is suggested to be of minor importance. Obvious hiatuses in Miocene to Pleistocene sediments are related to ongoing erosion and re-excavation of an uplifting and rejuvenating landscape. PMID- 22053125 TI - Kink-like mode of a double gradient instability in a compressible plasma current sheet. AB - A linear MHD instability of the electric current sheet, characterized by a small normal magnetic field component, varying along the sheet, is investigated. The tangential magnetic field component is modeled by a hyperbolic function, describing Harris-like variations of the field across the sheet. For this problem, which is formulated in a 3D domain, the conventional compressible ideal MHD equations are applied. By assuming Fourier harmonics along the electric current, the linearized 3D equations are reduced to 2D ones. A finite difference numerical scheme is applied to examine the time evolution of small initial perturbations of the plasma parameters. This work is an extended numerical study of the so called "double gradient instability", - a possible candidate for the explanation of flapping oscillations in the magnetotail current sheet, which has been analyzed previously in the framework of a simplified analytical approach for an incompressible plasma. The dispersion curve is obtained for the kink-like mode of the instability. It is shown that this curve demonstrates a quantitative agreement with the previous analytical result. The development of the instability is investigated also for various enhanced values of the normal magnetic field component. It is found that the characteristic values of the growth rate of the instability shows a linear dependence on the square root of the parameter, which scales uniformly the normal component of the magnetic field in the current sheet. PMID- 22053126 TI - The contribution of cell-cell signaling and motility to bacterial biofilm formation. AB - Many bacteria grow attached to a surface as biofilms. Several factors dictate biofilm formation, including responses by the colonizing bacteria to their environment. Here we review how bacteria use cell-cell signaling (also called quorum sensing) and motility during biofilm formation. Specifically, we describe quorum sensing and surface motility exhibited by the bacterium Pseudomonas aeruginosa, a ubiquitous environmental organism that acts as an opportunistic human pathogen in immunocompromised individuals. P. aeruginosa uses acyl homoserine lactone signals during quorum sensing to synchronize gene expression important to the production of polysaccharides, rhamnolipid, and other virulence factors. Surface motility affects the assembly and architecture of biofilms, and some aspects of motility are also influenced by quorum sensing. While some genes and their function are specific to P. aeruginosa, many aspects of biofilm development can be used as a model system to understand how bacteria differentially colonize surfaces. PMID- 22053127 TI - Structurally Diverse Nitric Oxide-Releasing Poly(propylene Imine) Dendrimers. AB - Structurally diverse secondary amine-functionalized poly(propylene imine) (PPI) dendrimers capable of tunable nitric oxide (NO) release were synthesized in a straightforward, one-step manner using ring-opening or conjugate-addition reactions with propylene oxide (PO), styrene oxide (SO), acrylonitrile (ACN), poly(ethylene glycol) methyl ether acrylate (average Mn = 480) (PEG) or 1,2-epoxy 9-decene (ED). N-Diazeniumdiolate nitric oxide donors were formed on the resulting secondary amine-functionalized G2-G5 PPI dendrimers by reaction with NO gas in basic solution. The NO storage and release kinetics for the resulting dendritic scaffolds were diverse (0.9-3.8 MUmol NO/mg totals and 0.3 to 4.9 h half lives), illustrating the importance of the exterior chemical modification (e.g., steric environments, hydrophobicity, etc.) on diazeniumdiolate stability/decomposition. Tunable NO release was demonstrated by combining two donor systems on the exterior of one macromolecular scaffold. Additionally, a mathematical model was developed that allows for the simulation of dual NO release kinetics using the NO release data from the two single NO donor systems. The approaches described herein extend the range and scope of NO-releasing macromolecular scaffolds by unlocking a series of materials for use as dopants in biomedical polymers or stand-alone therapeutics depending on the exterior modification. PMID- 22053146 TI - Rapid and accurate developmental stage recognition of C. elegans from high throughput image data. AB - We present a hierarchical principle for object recognition and its application to automatically classify developmental stages of C. elegans animals from a population of mixed stages. The object recognition machine consists of four hierarchical layers, each composed of units upon which evaluation functions output a label score, followed by a grouping mechanism that resolves ambiguities in the score by imposing local consistency constraints. Each layer then outputs groups of units, from which the units of the next layer are derived. Using this hierarchical principle, the machine builds up successively more sophisticated representations of the objects to be classified. The algorithm segments large and small objects, decomposes objects into parts, extracts features from these parts, and classifies them by SVM. We are using this system to analyze phenotypic data from C. elegans high-throughput genetic screens, and our system overcomes a previous bottleneck in image analysis by achieving near real-time scoring of image data. The system is in current use in a functioning C. elegans laboratory and has processed over two hundred thousand images for lab users. PMID- 22053147 TI - Active suppression of distractors that match the contents of visual working memory. AB - The biased competition theory proposes that items matching the contents of visual working memory will automatically have an advantage in the competition for attention. However, evidence for an automatic effect has been mixed, perhaps because the memory-driven attentional bias can be overcome by top-down suppression. To test this hypothesis, the Pd component of the event-related potential waveform was used as a marker of attentional suppression. While observers maintained a color in working memory, task-irrelevant probe arrays were presented that contained an item matching the color being held in memory. We found that the memory-matching probe elicited a Pd component, indicating that it was being actively suppressed. This result suggests that sensory inputs matching the information being held in visual working memory are automatically detected and generate an "attend-to-me" signal, but this signal can be overridden by an active suppression mechanism to prevent the actual capture of attention. PMID- 22053148 TI - Seeing the destination but not the path: Effects of socioeconomic disadvantage on school-focused possible self content and linked behavioral strategies. AB - Low-income children perform better in school when school-focused future identities are a salient aspect of their possible self for the coming year and these school-focused future identities are linked to behavioral strategies (Oyserman et al., 2006). Hierarchical linear modeling of data from a four-state low-income neighborhood sample of eighth-graders suggests two central consequences of family and neighborhood socioeconomic deprivation on children's school-focused possible identities and strategies. First, higher neighborhood disadvantage is associated with greater salience of school in children's possible self for the coming year. Second, disadvantage clouds the path to school-success; controlling for salience of school-focused possible identities, children living in lower socioeconomic status families and boys living in more economically disadvantaged neighborhoods were less likely to have strategies to attain their school-focused possible identities. The influence of family socioeconomic status was seen particularly with regard to strategies to attain academic success and teacher engagement aspects of school-focused identities. PMID- 22053149 TI - Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics. AB - Having demonstrated significant and persistent adverse changes in pulmonary function for asthmatics after 1 hour exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols, we assessed the possible longer term health effects in asthmatics from intermittent environmental exposure to brevetoxins over 7 years. 125 asthmatic subjects were assessed for their pulmonary function and reported symptoms before and after 1 hour of environmental exposure to Florida red tide aerosols for upto 11 studies over seven years. As a group, the asthmatics came to the studies with normal standardized percent predicted pulmonary function values. The 38 asthmatics who participated in only one exposure study were more reactive compared to the 36 asthmatics who participated in >=4 exposure studies. The 36 asthmatics participating in >=4 exposure studies demonstrated no significant change in their standardized percent predicted pre exposure pulmonary function over the 7 years of the study. These results indicate that stable asthmatics living in areas with intermittent Florida red tides do not exhibit chronic respiratory effects from intermittent environmental exposure to aerosolized brevetoxins over a 7 year period. PMID- 22053150 TI - Regulation of neural stem cell in the human SVZ by trophic and morphogenic factors. AB - The subventricular zone (SVZ), lining the lateral ventricular system, is the largest germinal region in mammals. In there, neural stem cells express markers related to astoglial lineage that give rise to new neurons and oligodendrocytes in vivo. In the adult human brain, in vitro evidence has also shown that astrocytic cells isolated from the SVZ can generate new neurons and oligodendrocytes. These proliferative cells are strongly controlled by a number of signals and molecules that modulate, activate or repress the cell division, renewal, proliferation and fate of neural stem cells. In this review, we summarize the cellular composition of the adult human SVZ (hSVZ) and discuss the increasing evidence showing that some trophic modulators strongly control the function of neural stem cells in the SVZ. PMID- 22053151 TI - Glycogen synthase kinase-3: a promising therapeutic target for fragile x syndrome. AB - Recent advances in understanding the pathophysiological mechanisms contributing to fragile X syndrome (FXS) have increased optimism that drug interventions can provide significant therapeutic benefits. FXS results from inadequate expression of functional fragile X mental retardation protein (FMRP). FMRP may have several functions, but it is most well-established as an RNA binding protein that regulates translation, and it is thought that by this mechanism FMRP is capable of affecting numerous cellular processes by selectively regulating protein levels. The multiple cellular functions regulated by FMRP suggest that multiple interventions may be required for reversing the effects of deficient FMRP. Evidence that inhibitors of glycogen synthase kinase-3 (GSK3) may contribute to the therapeutic treatment of FXS is reviewed here. Lithium, a GSK3 inhibitor, improved function in the Drosophila model of FXS. In mice lacking FMRP expression (FX mice), GSK3 is hyperactive in several brain regions. Significant improvements in several FX-related phenotypes have been obtained in FX mice following the administration of lithium, and in some case other GSK3 inhibitors. These responses include normalization of heightened audiogenic seizure susceptibility and of hyperactive locomotor behavior, enhancement of passive avoidance learning retention and of sociability behaviors, and corrections of macroorchidism, neuronal spine density, and neural plasticity measured electrophysiologically as long term depression. A pilot clinical trial of lithium in patients with FXS also found improvements in several measures of behavior. Taken together, these findings indicate that lithium and other inhibitors of GSK3 are promising candidate therapeutic agents for treating FXS. PMID- 22053152 TI - Preliminary Evidence of Pre-Attentive Distinctions of Frequency-Modulated Tones that Convey Affect. AB - Recognizing emotion is an evolutionary imperative. An early stage of auditory scene analysis involves the perceptual grouping of acoustic features, which can be based on both temporal coincidence and spectral features such as perceived pitch. Perceived pitch, or fundamental frequency (F(0)), is an especially salient cue for differentiating affective intent through speech intonation (prosody). We hypothesized that: (1) simple frequency-modulated tone abstractions, based on the parameters of actual prosodic stimuli, would be reliably classified as representing differing emotional categories; and (2) that such differences would yield significant mismatch negativities (MMNs) - an index of pre-attentive deviance detection within the auditory environment. We constructed a set of FM tones that approximated the F(0) mean and variation of reliably recognized happy and neutral prosodic stimuli. These stimuli were presented to 13 subjects using a passive listening oddball paradigm. We additionally included stimuli with no frequency modulation (FM) and FM tones with identical carrier frequencies but differing modulation depths as control conditions. Following electrophysiological recording, subjects were asked to identify the sounds they heard as happy, sad, angry, or neutral. We observed that FM tones abstracted from happy and no expression speech stimuli elicited MMNs. Post hoc behavioral testing revealed that subjects reliably identified the FM tones in a consistent manner. Finally, we also observed that FM tones and no-FM tones elicited equivalent MMNs. MMNs to FM tones that differentiate affect suggests that these abstractions may be sufficient to characterize prosodic distinctions, and that these distinctions can be represented in pre-attentive auditory sensory memory. PMID- 22053154 TI - Beyond Extrastriate Body Area (EBA) and Fusiform Body Area (FBA): Context Integration in the Meaning of Actions. PMID- 22053153 TI - Pre-chemotherapy differences in visuospatial working memory in breast cancer patients compared to controls: an FMRI study. AB - INTRODUCTION: Cognitive deficits are a side-effect of chemotherapy, however pre treatment research is limited. This study examines neurofunctional differences during working memory between breast cancer (BC) patients and controls, prior to chemotherapy. METHODS: Early stage BC females (23), scanned after surgery but before chemotherapy, were individually matched to non-cancer controls. Participants underwent functional magnetic resonance imaging (fMRI) while performing a Visuospatial N-back task and data was analyzed by multiple group comparisons. fMRI task performance, neuropsychological tests, hospital records, and salivary biomarkers were also collected. RESULTS: There were no significant group differences on neuropsychological tests, estrogen, or cortisol. Patients made significantly fewer commission errors but had less overall correct responses and were slower than controls during the task. Significant group differences were observed for the fMRI data, yet results depended on the type of analysis. BC patients presented with increased activations during working memory compared to controls in areas such as the inferior frontal gyrus, insula, thalamus, and midbrain. Individual group regressions revealed a reverse relationship between brain activity and commission errors. CONCLUSION: This is the first fMRI investigation to reveal neurophysiological differences during visuospatial working memory between BC patients pre-chemotherapy and controls. These results also increase the knowledge about the effects of BC and related factors on the working memory network. SIGNIFICANCE: This highlights the need to better understand the pre-chemotherapy BC patient and the effects of associated confounding variables. PMID- 22053155 TI - Knowledge synthesis with maps of neural connectivity. AB - This paper describes software for neuroanatomical knowledge synthesis based on neural connectivity data. This software supports a mature methodology developed since the early 1990s. Over this time, the Swanson laboratory at USC has generated an account of the neural connectivity of the sub-structures of the hypothalamus, amygdala, septum, hippocampus, and bed nucleus of the stria terminalis. This is based on neuroanatomical data maps drawn into a standard brain atlas by experts. In earlier work, we presented an application for visualizing and comparing anatomical macro connections using the Swanson third edition atlas as a framework for accurate registration. Here we describe major improvements to the NeuARt application based on the incorporation of a knowledge representation of experimental design. We also present improvements in the interface and features of the data mapping components within a unified web application. As a step toward developing an accurate sub-regional account of neural connectivity, we provide navigational access between the data maps and a semantic representation of area-to-area connections that they support. We do so based on an approach called "Knowledge Engineering from Experimental Design" (KEfED) model that is based on experimental variables. We have extended the underlying KEfED representation of tract-tracing experiments by incorporating the definition of a neuronanatomical data map as a measurement variable in the study design. This paper describes the software design of a web-application that allows anatomical data sets to be described within a standard experimental context and thus indexed by non-spatial experimental design features. PMID- 22053156 TI - The sodium channel as a target for local anesthetic drugs. AB - Na channels are the source of excitatory currents for the nervous system and muscle. They are the target for a class of drugs called local anesthetics (LA), which have been used for local and regional anesthesia and for excitatory problems such as epilepsy and cardiac arrhythmia. These drugs are prototypes for new analgesic drugs. The drug-binding site has been localized to the inner pore of the channel, where drugs interact mainly with a phenylalanine in domain IV S6. Drug affinity is both voltage- and use-dependent. Voltage-dependency is the result of changes in the conformation of the inner pore during channel activation and opening, allowing high energy interaction of drugs with the phenylalanine. LA drugs also reduce the gating current of Na channels, which represents the movement of charged residues in the voltage sensors. Specifically, drug binding to phenylalanine locks the domain III S4 in its outward (activated) position, and slows recovery of the domain IV S4. Although strongly affecting gating, LA drugs almost certainly also block by steric occlusion of the pore. Molecular definition of the binding and blocking interactions may help in new drug development. PMID- 22053157 TI - Tube-load model parameter estimation for monitoring arterial hemodynamics. AB - A useful model of the arterial system is the uniform, lossless tube with parametric load. This tube-load model is able to account for wave propagation and reflection (unlike lumped-parameter models such as the Windkessel) while being defined by only a few parameters (unlike comprehensive distributed-parameter models). As a result, the parameters may be readily estimated by accurate fitting of the model to available arterial pressure and flow waveforms so as to permit improved monitoring of arterial hemodynamics. In this paper, we review tube-load model parameter estimation techniques that have appeared in the literature for monitoring wave reflection, large artery compliance, pulse transit time, and central aortic pressure. We begin by motivating the use of the tube-load model for parameter estimation. We then describe the tube-load model, its assumptions and validity, and approaches for estimating its parameters. We next summarize the various techniques and their experimental results while highlighting their advantages over conventional techniques. We conclude the review by suggesting future research directions and describing potential applications. PMID- 22053158 TI - Growth patterns of neuropsychological functions in Indian children. AB - We investigated age-related differences in neuropsychological performance in 400 Indian school children (5-15 years of age). Functions of motor speed, attention, executive functions, visuospatial functions, comprehension, learning, and memory were examined. Growth curve analysis was performed. Different growth models fitted different cognitive functions. Neuropsychological task performance improved slowly between 5 and 7 years, moderately between 8 and 12 years and slowly between 13 and 15 years of age. The overall growth patterns of neuropsychological functions in Indian children have been discussed with the findings reported on American children. The present work describes non-linear, heterogeneous, and protracted age trends of neuropsychological functions in Indian children and adolescents. PMID- 22053159 TI - Feature integration across the lifespan: stickier stimulus-response bindings in children and older adults. AB - Humans integrate the features of perceived events and of action plans into episodic event files. Here we investigated whether children (9-10 years), younger adults (20-31 years), and older adults (64-76 years) differ in the flexibility of managing (updating) event files. Relative to young adults, performance in children and older adults was more hampered by partial mismatches between present and previous stimulus-response relations, suggesting less efficient updating of episodic stimulus-response representations in childhood and old age. Results are discussed in relation to changes in cortical neurochemistry during maturation and senescence. PMID- 22053160 TI - Comparing word processing times in naming, lexical decision, and progressive demasking: evidence from chronolex. AB - We report performance measures for lexical decision (LD), word naming (NMG), and progressive demasking (PDM) for a large sample of monosyllabic monomorphemic French words (N = 1,482). We compare the tasks and also examine the impact of word length, word frequency, initial phoneme, orthographic and phonological distance to neighbors, age-of-acquisition, and subjective frequency. Our results show that objective word frequency is by far the most important variable to predict reaction times in LD. For word naming, it is the first phoneme. PDM was more influenced by a semantic variable (word imageability) than LD, but was also affected to a much greater extent by perceptual variables (word length, first phoneme/letters). This may reduce its usefulness as a psycholinguistic word recognition task. PMID- 22053161 TI - "Delivering knowledge and advice": Healthcare providers' experiences of their interaction with patients' management of rheumatoid arthritis. AB - Rheumatic diseases are often chronic and involve a lifetime of suffering. The focus of rheumatology care is to support patients to manage their lives and master their disease. Healthcare providers and patients have different views on the consequences of living with rheumatic diseases and patients are reporting unmet healthcare needs. There is a need to integrate providers' perspective to develop the quality of rheumatology care. The aim was to explore healthcare providers' experiences of their interaction with patients in their management of RA. Interviews with 18 providers from different clinical settings were analysed in accordance with the grounded theory method. A core category; Delivering knowledge and advice was found to be the most important task and involved providing the patient with information about the disease and appropriate forms of treatment. Healthcare providers' attitudes and patients' responses influenced the outcome of the delivery of knowledge and advice and three dimensions emerged; completed delivery, adjusted delivery and failed delivery. There were differences in the providers' experiences in their interaction with patients as well as in reflections on their role as the delivering part. There could be difficulties in the interaction when patients' expectations and preferences were not taken into account when giving advice. These findings highlight the importance of developing rheumatology care, as no provider or patient benefits if the delivery of knowledge and advice becomes a failed delivery. The healthcare organization must acknowledge the difficulties involved in the interaction with patients in their management of RA and find methods to develop a more person-centred approach to care. PMID- 22053162 TI - Torrenting values, feelings, and thoughts-Cyber nursing and virtual self-care in a breast augmentation forum. AB - Earlier research shows that breast augmentation is positively correlated with positive psychological states. The aim of this study was to explore the shared values, feelings, and thoughts within the culture of breast enlargement among women visiting Internet-based forums when considering and/or undergoing esthetic plastic surgery. The study used a netnographic method for gathering and analyzing data. The findings show that the women used the Internet forum to provide emotional support to other women. Through electronic postings, they cared for and nursed each others' anxiety and feelings throughout the whole process. Apart from the process, another central issue was that the women's relationships were frequently discussed; specifically their relationship to themselves, their environment, and with the surgeons. The findings suggest that Internet forums represent a channel through which posters can share values, feelings, and thoughts from the position of an agent of action as well as from a position as the object of action. These dual positions and the medium endow the women with a virtual nursing competence that would otherwise be unavailable. By introducing the concept of torrenting as a means of sharing important self-care information, the authors provide a concept that can be further explored in relation to post modern self-care strategies within contemporary nursing theories and practice. PMID- 22053163 TI - IMAGING: Focusing light in scattering media. AB - Combining ultrasonic modulation and optical phase conjugation allows light to be tightly focused in a scattering medium, providing benefits for studies of photophysical, photochemical and photobiological processes. PMID- 22053164 TI - Idiopathic simultaneous bilateral Achilles tendon rupture. AB - Cases of simultaneous bilateral rupture of the Achilles tendon are extremely rare and usually associated with other pathology. Our patient was a healthy, previously asymptomatic 33-year-old woman with no obvious predisposing factors other than a remote history of involvement in gymnastics. The patient opted for surgical management which resulted in a favourable outcome. PMID- 22053165 TI - Acute renal failure followed by low back ache. PMID- 22053166 TI - Contrast induced hyperthyroidism due to iodine excess. AB - Iodine induced hyperthyroidism is a thyrotoxic condition caused by exposure to excessive iodine. Historically this type of hyperthyroidism has been described in areas of iodine deficiency. With advances in medicine, iodine induced hyperthyroidism has been observed following the use of drugs containing iodine for example, amiodarone, and contrast agents used in radiological imaging. In elderly patients it is frequently difficult to diagnose and control contrast related hyperthyroidism, as most of these patients do not always present with typical signs and symptoms of hyperthyroidism. Treatment can be very challenging as drugs commonly used to treat hyperthyroidism have little effect on already formed thyroid hormone due to iodine excess. PMID- 22053167 TI - Sudden death caused by Staphylococcus aureus carrying Panton-Valentine leukocidin gene in a young girl. AB - Staphylococcus aureus carrying the Panton-Valentine leukocidin (PVL) gene could be the source of both recurrent furunculosis or abscesses and severe infections, mainly necrotising pneumonia. We present the case of a young girl from consanguineous parents who died suddenly. The postmortem examination revealed necrotising pneumonia due to a PVL producing Staphylococcus aureus strain, raising the question of the role of the host's immune status in this infection. PMID- 22053168 TI - Why not? - Communicating stochastic information by use of unsorted frequency pictograms - a randomised controlled trial. AB - OBJECTIVE: Statistical health risk information has been proven confusing and difficult to understand. While existing research indicates that presenting risk information in frequency formats is superior to relative risk and probability formats, the optimal design of frequency formats is still unclear. The aim of this study was to compare presentation of multi-figure pictographs in consecutive and random arrangements regarding accuracy in perception and vulnerability for cognitive bias. METHODS: A total of 111 patients with multiple sclerosis were randomly assigned to two experimental conditions: patient information using 100 figure pictographs in 1) unsorted (UP group) or 2) consecutive arrangement (CP group).The study experiment was framed as patient information on how risks and benefit could be explained. The information comprised two scenarios of a treatment decision with varying levels of emotional relevance. Primary outcome measure was accuracy of information recall (errors made when recalling previously presented frequencies of benefits and side effects). Cognitive bias was measured as additional error appearing with higher emotional involvement. The uncertainty tolerance scale and a set of items to assess risk attribution were surveyed. RESULTS: The study groups did not differ in their accuracy of recalling benefits, but recall of side effects was more accurate in the CP-group. Cognitive bias when recalling benefits was higher in the UP-group than in the CP-group and equal for side effects in both groups. RESULTS were similar in subgroup analyses of patients 1) with highly irrational risk attribution 2) with experience regarding the hypothetical contents or 3) with experience regarding pictograph presentation of frequencies. Overall, benefit was overestimated by more than 100% and variance of recall was extremely high. CONCLUSIONS: Consecutive arrangement as commonly used seems not clearly superior to unsorted arrangement which is more close to reality. General poor performance and the corresponding high variance of recall might have clouded existing effects of the arrangement types. More research is needed with varying proportions and other samples. PMID- 22053169 TI - The Protective Effects of Ischemic Postconditioning against Stroke: From Rapid to Delayed and Remote Postconditioning. AB - The author reviews the protective effects of ischemic postconditioning, a recently emerging strategy with broad implications in the search for new treatments in stroke and myocardial ischemic injury. Ischemic postconditioning, which refers to a series of brief ischemia and reperfusion cycles applied immediately at the site of the ischemic organ after reperfusion, results in reduced infarction in both cerebral and myocardial ischemia. Conventional postconditioning induced within a few minutes after reperfusion is arbitrarily defined as rapid postconditioning. In contrast, postconditioning performed hours to days after stroke is defined as delayed postconditioning. In addition, postconditioning can be mimicked using anesthetics or other pharmacological agents as stimuli to protect against ischemia/reperfusion injury or performed in a distant organ, which is known as remote postconditioning. In this article, the author discusses the conceptual origin of classical rapid ischemic postconditioning and its evolution into a term that represents a broad range of stimuli or triggers, including delayed postconditioning, pharmacological postconditioning, and remote postconditioning. Thereafter, various in vivo and in vitro models of postconditioning and its potential protective mechanisms are discussed. Since the concept of postconditioning is so closely associated with that of preconditioning and both share some common protective mechanisms, whether a combination of preconditioning and postconditioning offers greater protection than preconditioning or postconditioning alone is also discussed. PMID- 22053170 TI - Time to put the CAR-T before the horse. PMID- 22053171 TI - Lymphoma spread? Target CD47-SIRPalpha! PMID- 22053172 TI - Released on a WHIM. PMID- 22053173 TI - Th1 and Th17 join forces for acute GVHD. PMID- 22053174 TI - Ang2, the instigator of inflammation. PMID- 22053175 TI - On the measurement of movement difficulty in the standard approach to Fitts' law. AB - Fitts' law is an empirical rule of thumb which predicts the time it takes people, under time pressure, to reach with some pointer a target of width W located at a distance D. It has been traditionally assumed that the predictor of movement time must be some mathematical transform of the quotient of D/W, called the index of difficulty (ID) of the movement task. We ask about the scale of measurement involved in this independent variable. We show that because there is no such thing as a zero-difficulty movement, the IDs of the literature run on non-ratio scales of measurement. One notable consequence is that, contrary to a widespread belief, the value of the y-intercept of Fitts' law is uninterpretable. To improve the traditional Fitts paradigm, we suggest grounding difficulty on relative target tolerance W/D, which has a physical zero, unlike relative target distance D/W. If no one can explain what is meant by a zero-difficulty movement task, everyone can understand what is meant by a target layout whose relative tolerance W/D is zero, and hence whose relative intolerance 1-W/D is 1 or 100%. We use the data of Fitts' famous tapping experiment to illustrate these points. Beyond the scale of measurement issue, there is reason to doubt that task difficulty is the right object to try to measure in basic research on Fitts' law, target layout manipulations having never provided users of the traditional Fitts paradigm with satisfactory control over the variations of the speed and accuracy of movements. We advocate the trade-off paradigm, a recently proposed alternative, which is immune to this criticism. PMID- 22053176 TI - Beyond genetic factors in familial amyloidotic polyneuropathy: protein glycation and the loss of fibrinogen's chaperone activity. AB - Familial amyloidotic polyneuropathy (FAP) is a systemic conformational disease characterized by extracellular amyloid fibril formation from plasma transthyretin (TTR). This is a crippling, fatal disease for which liver transplantation is the only effective therapy. More than 80 TTR point mutations are associated with amyloidotic diseases and the most widely accepted disease model relates TTR tetramer instability with TTR point mutations. However, this model fails to explain two observations. First, native TTR also forms amyloid in systemic senile amyloidosis, a geriatric disease. Second, age at disease onset varies by decades for patients bearing the same mutation and some mutation carrier individuals are asymptomatic throughout their lives. Hence, mutations only accelerate the process and non-genetic factors must play a key role in the molecular mechanisms of disease. One of these factors is protein glycation, previously associated with conformational diseases like Alzheimer's and Parkinson's. The glycation hypothesis in FAP is supported by our previous discovery of methylglyoxal-derived glycation of amyloid fibrils in FAP patients. Here we show that plasma proteins are differentially glycated by methylglyoxal in FAP patients and that fibrinogen is the main glycation target. Moreover, we also found that fibrinogen interacts with TTR in plasma. Fibrinogen has chaperone activity which is compromised upon glycation by methylglyoxal. Hence, we propose that methylglyoxal glycation hampers the chaperone activity of fibrinogen, rendering TTR more prone to aggregation, amyloid formation and ultimately, disease. PMID- 22053177 TI - Differential requirement for cathepsin D for processing of the full length and C terminal fragment of the malaria antigen MSP1. AB - Merozoite Surface Protein 1 is expressed on the surface of malaria merozoites and is important for invasion of the malaria parasite into erythrocytes. MSP1 specific CD4 T cell responses and antibody can confer protective immunity in experimental models of malaria. In this study we explore the contributions of cathepsins D and E, two aspartic proteinases previously implicated in antigen processing, to generating MSP1 CD4 T-cell epitopes for presentation. The absence of cathepsin D, a late endosome/lysosomal enzyme, is associated with a reduced presentation of MSP1 both following in vitro processing of the epitope MSP1 from infected erythrocytes by bone marrow-derived dendritic cells, and following in vivo processing by splenic CD11c+ dendritic cells. By contrast, processing and presentation of the soluble recombinant protein fragment of MSP1 is unaffected by the absence of cathepsin D, but is inhibited when both cathepsin D and E are absent. The role of different proteinases in generating the CD4 T cell repertoire, therefore, depends on the context in which an antigen is introduced to the immune system. PMID- 22053178 TI - Identification of microRNAs as potential prognostic markers in ependymoma. AB - INTRODUCTION: We have examined expression of microRNAs (miRNAs) in ependymomas to identify molecular markers of value for clinical management. miRNAs are non coding RNAs that can block mRNA translation and affect mRNA stability. Changes in the expression of miRNAs have been correlated with many human cancers. MATERIALS AND METHODS: We have utilized TaqMan Low Density Arrays to evaluate the expression of 365 miRNAs in ependymomas and normal brain tissue. We first demonstrated the similarity of expression profiles of paired frozen tissue (FT) and paraffin-embedded specimens (FFPE). We compared the miRNA expression profiles of 34 FFPE ependymoma samples with 8 microdissected normal brain tissue specimens enriched for ependymal cells. miRNA expression profiles were then correlated with tumor location, histology and other clinicopathological features. RESULTS: We have identified miRNAs that are over-expressed in ependymomas, such as miR-135a and miR-17-5p, and down-regulated, such as miR-383 and miR-485-5p. We have also uncovered associations between expression of specific miRNAs which portend a worse prognosis. For example, we have identified a cluster of miRNAs on human chromosome 14q32 that is associated with time to relapse. We also found that miR 203 is an independent marker for relapse compared to the parameters that are currently used. Additionally, we have identified three miRNAs (let-7d, miR-596 and miR-367) that strongly correlate to overall survival. CONCLUSION: We have identified miRNAs that are differentially expressed in ependymomas compared with normal ependymal tissue. We have also uncovered significant associations of miRNAs with clinical behavior. This is the first report of clinically relevant miRNAs in ependymomas. PMID- 22053179 TI - Activity-dependent changes in cholinergic innervation of the mouse olfactory bulb. AB - The interplay between olfactory activity and cholinergic modulation remains to be fully understood. This report examines the pattern of cholinergic innervation throughout the murine main olfactory bulb across different developmental stages and in naris-occluded animals. To visualize the pattern of cholinergic innervation, we used a transgenic mouse model, which expresses a fusion of the microtubule-associated protein, tau, with green fluorescence protein (GFP) under the control of the choline acetyltransferase (ChAT) promoter. This tau-GFP fusion product allows for a remarkably vivid and clear visualization of cholinergic innervation in the main olfactory bulb (MOB). Interestingly, we find an uneven distribution of GFP label in the adult glomerular layer (GL), where anterior, medial, and lateral glomerular regions of the bulb receive relatively heavier cholinergic innervation than other regions. In contrast to previous reports, we find a marked change in the pattern of cholinergic innervation to the GL following unilateral naris occlusion between the ipsilateral and contralateral bulbs in adult animals. PMID- 22053180 TI - Dengue type 4 live-attenuated vaccine viruses passaged in vero cells affect genetic stability and dengue-induced hemorrhaging in mice. AB - Most live-attenuated tetravalent dengue virus vaccines in current clinical trials are produced from Vero cells. In a previous study we demonstrated that an infectious cDNA clone-derived dengue type 4 (DEN-4) virus retains higher genetic stability in MRC-5 cells than in Vero cells. For this study we investigated two DEN-4 viruses: the infectious cDNA clone-derived DEN-4 2A and its derived 3' NCR 30-nucleotide deletion mutant DEN-4 2ADelta30, a vaccine candidate. Mutations in the C-prM-E, NS2B-NS3, and NS4B-NS5 regions of the DEN genome were sequenced and compared following cell passages in Vero and MRC-5 cells. Our results indicate stronger genetic stability in both viruses following MRC-5 cell passages, leading to significantly lower RNA polymerase error rates when the DEN-4 virus is used for genome replication. Although no significant increases in virus titers were observed following cell passages, DEN-4 2A and DEN-4 2ADelta30 virus titers following Vero cell passages were 17-fold to 25-fold higher than titers following MRC-5 cell passages. Neurovirulence for DEN-4 2A and DEN-4 2ADelta30 viruses increased significantly following passages in Vero cells compared to passages in MRC-5 cells. In addition, more severe DEN-induced hemorrhaging in mice was noted following DEN-4 2A and DEN-4 2ADelta30 passages in Vero cells compared to passages in MRC-5 cells. Target mutagenesis performed on the DEN-4 2A infectious clone indicated that single point mutation of E-Q(438)H, E-V(463)L, NS2B-Q(78)H, and NS2B-A(113)T imperatively increased mouse hemorrhaging severity. The relationship between amino acid mutations acquired during Vero cell passage and enhanced DEN-induced hemorrhages in mice may be important for understanding DHF pathogenesis, as well as for the development of live-attenuated dengue vaccines. Taken together, the genetic stability, virus yield, and DEN-induced hemorrhaging all require further investigation in the context of live-attenuated DEN vaccine development. PMID- 22053181 TI - Altered antibiotic transport in OmpC mutants isolated from a series of clinical strains of multi-drug resistant E. coli. AB - Antibiotic-resistant bacteria, particularly gram negative species, present significant health care challenges. The permeation of antibiotics through the outer membrane is largely effected by the porin superfamily, changes in which contribute to antibiotic resistance. A series of antibiotic resistant E. coli isolates were obtained from a patient during serial treatment with various antibiotics. The sequence of OmpC changed at three positions during treatment giving rise to a total of four OmpC variants (denoted OmpC20, OmpC26, OmpC28 and OmpC33, in which OmpC20 was derived from the first clinical isolate). We demonstrate that expression of the OmpC K12 porin in the clinical isolates lowers the MIC, consistent with modified porin function contributing to drug resistance. By a range of assays we have established that the three mutations that occur between OmpC20 and OmpC33 modify transport of both small molecules and antibiotics across the outer membrane. This results in the modulation of resistance to antibiotics, particularly cefotaxime. Small ion unitary conductance measurements of the isolated porins do not show significant differences between isolates. Thus, resistance does not appear to arise from major changes in pore size. Crystal structures of all four OmpC clinical mutants and molecular dynamics simulations also show that the pore size is essentially unchanged. Molecular dynamics simulations suggest that perturbation of the transverse electrostatic field at the constriction zone reduces cefotaxime passage through the pore, consistent with laboratory and clinical data. This subtle modification of the transverse electric field is a very different source of resistance than occlusion of the pore or wholesale destruction of the transverse field and points to a new mechanism by which porins may modulate antibiotic passage through the outer membrane. PMID- 22053182 TI - Temporal information processing in short- and long-term memory of patients with schizophrenia. AB - Cognitive deficits of patients with schizophrenia have been largely recognized as core symptoms of the disorder. One neglected factor that contributes to these deficits is the comprehension of time. In the present study, we assessed temporal information processing and manipulation from short- and long-term memory in 34 patients with chronic schizophrenia and 34 matched healthy controls. On the short term memory temporal-order reconstruction task, an incidental or intentional learning strategy was deployed. Patients showed worse overall performance than healthy controls. The intentional learning strategy led to dissociable performance improvement in both groups. Whereas healthy controls improved on a performance measure (serial organization), patients improved on an error measure (inappropriate semantic clustering) when using the intentional instead of the incidental learning strategy. On the long-term memory script-generation task, routine and non-routine events of everyday activities (e.g., buying groceries) had to be generated in either chronological or inverted temporal order. Patients were slower than controls at generating events in the chronological routine condition only. They also committed more sequencing and boundary errors in the inverted conditions. The number of irrelevant events was higher in patients in the chronological, non-routine condition. These results suggest that patients with schizophrenia imprecisely access temporal information from short- and long term memory. In short-term memory, processing of temporal information led to a reduction in errors rather than, as was the case in healthy controls, to an improvement in temporal-order recall. When accessing temporal information from long-term memory, patients were slower and committed more sequencing, boundary, and intrusion errors. Together, these results suggest that time information can be accessed and processed only imprecisely by patients who provide evidence for impaired time comprehension. This could contribute to symptomatic cognitive deficits and strategic inefficiency in schizophrenia. PMID- 22053183 TI - Calcium signaling in live cells on elastic gels under mechanical vibration at subcellular levels. AB - A new device was designed to generate a localized mechanical vibration of flexible gels where human umbilical vein endothelial cells (HUVECs) were cultured to mechanically stimulate these cells at subcellular locations. A Fluorescence Resonance Energy Transfer (FRET)-based calcium biosensor (an improved Cameleon) was used to monitor the spatiotemporal distribution of intracellular calcium concentrations in the cells upon this mechanical stimulation. A clear increase in intracellular calcium concentrations over the whole cell body (global) can be observed in the majority of cells under mechanical stimulation. The chelation of extracellular calcium with EGTA or the blockage of stretch-activated calcium channels on the plasma membrane with streptomycin or gadolinium chloride significantly inhibited the calcium responses upon mechanical stimulation. Thapsigargin, an endoplasmic reticulum (ER) calcium pump inhibitor, or U73122, a phospholipase C (PLC) inhibitor, resulted in mainly local calcium responses occurring at regions close to the stimulation site. The disruption of actin filaments with cytochalasin D or inhibition of actomyosin contractility with ML-7 also inhibited the global calcium responses. Therefore, the global calcium response in HUVEC depends on the influx of calcium through membrane stretch activated channels, followed by the release of inositol trisphosphate (IP3) via PLC activation to trigger the ER calcium release. Our newly developed mechanical stimulation device can also provide a powerful tool for the study of molecular mechanism by which cells perceive the mechanical cues at subcellular levels. PMID- 22053184 TI - Selective over-expression of endothelin-1 in endothelial cells exacerbates inner retinal edema and neuronal death in ischemic retina. AB - The level of endothelin-1 (ET-1), a potent vasoconstrictor, was associated with retinopathy under ischemia. The effects of endothelial endothelin-1 (ET-1) over expression in a transgenic mouse model using Tie-1 promoter (TET-1 mice) on pathophysiological changes of retinal ischemia were investigated by intraluminal insertion of a microfilament up to middle cerebral artery (MCA) to transiently block the ophthalmic artery. Two-hour occlusion and twenty-two-hour reperfusion were performed in homozygous (Hm) TET-1 mice and their non-transgenic (NTg) littermates. Presence of pyknotic nuclei in ganglion cell layer (GCL) was investigated in paraffin sections of ipsilateral (ischemic) and contralateral (non-ischemic) retinae, followed by measurement of the thickness of inner retinal layer. Moreover, immunocytochemistry of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS) and aquaporin-4 (AQP4) peptides on retinal sections were performed to study glial cell reactivity, glutamate metabolism and water accumulation, respectively after retinal ischemia. Similar morphology was observed in the contralateral retinae of NTg and Hm TET-1 mice, whereas ipsilateral retina of NTg mice showed slight structural and cellular changes compared with the corresponding contralateral retina. Ipsilateral retinae of Hm TET-1 mice showed more significant changes when compared with ipsilateral retina of NTg mice, including more prominent cell death in GCL characterized by the presence of pyknotic nuclei, elevated GS immunoreactivity in Muller cell bodies and processes, increased AQP-4 immunoreactivity in Muller cell processes, and increased inner retinal thickness. Thus, over-expression of endothelial ET-1 in TET-1 mice may contribute to increased glutamate-induced neurotoxicity on neuronal cells and water accumulation in inner retina leading to edema. PMID- 22053185 TI - Contributions of histone H3 nucleosome core surface mutations to chromatin structures, silencing and DNA repair. AB - Histone H3 mutations in residues that cluster in a discrete region on the nucleosome surface around lysine 79 of H3 affect H3-K79 methylation, impair transcriptional silencing in subtelomeric chromatin, and reveal distinct contributions of histone H3 to various DNA-damage response and repair pathways. These residues might act by recruitment of silencing and DNA-damage response factors. Alternatively, their location on the nucleosome surface suggests a possible involvement in nucleosome positioning, stability and nucleosome interactions. Here, we show that the yeast H3 mutants hht2-T80A, hht2-K79E, hht2 L70S, and hht2-E73D show normal nucleosome positioning and stability in minichromosomes. However, loss of silencing in a subtelomeric URA3 gene correlates with a shift of the promoter nucleosome, while nucleosome positions and stability in the coding region are maintained. Moreover, the H3 mutants show normal repair of UV lesions by photolyase and nucleotide excision repair in minichromosomes and slightly enhanced repair in the subtelomeric region. Thus, these results support a role of those residues in the recruitment of silencing proteins and argue against a general role in nucleosome organization. PMID- 22053186 TI - Fine-scale genetic structure arises during range expansion of an invasive gecko. AB - Processes of range expansion are increasingly important in light of current concerns about invasive species and range shifts due to climate change. Theoretical studies suggest that genetic structuring may occur during range expansion. Ephemeral genetic structure can have important evolutionary implications, such as propagating genetic changes along the wave front of expansion, yet few studies have shown evidence of such structure. We tested the hypothesis that genetic structure arises during range expansion in Hemidactylus mabouia, a nocturnal African gecko recently introduced to Florida, USA. Twelve highly variable microsatellite loci were used to screen 418 individuals collected from 43 locations from four sampling sites across Florida, representing a gradient from earlier (~1990s) to very recent colonization. We found earlier colonized locations had little detectable genetic structure and higher allelic richness than more recently colonized locations. Genetic structuring was pronounced among locations at spatial scales of tens to hundreds of meters near the leading edge of range expansion. Despite the rapid pace of range expansion in this introduced gecko, dispersal is limited among many suitable habitat patches. Fine-scale genetic structure is likely the result of founder effects during colonization of suitable habitat patches. It may be obscured over time and by scale-dependent modes of dispersal. Further studies are needed to determine if such genetic structure affects adaptation and trait evolution in range expansions and range shifts. PMID- 22053187 TI - Hydrocarbon contamination decreases mating success in a marine planktonic copepod. AB - The mating behavior and the mating success of copepods rely on chemoreception to locate and track a sexual partner. However, the potential impact of the water soluble fraction of hydrocarbons on these aspects of copepod reproduction has never been tested despite the widely acknowledged acute chemosensory abilities of copepods. I examined whether three concentrations of the water-soluble fraction of diesel oil (0.01%, 0.1% and 1%) impacts (i) the swimming behavior of both adult males and females of the widespread calanoid copepod Temora longcornis, and (ii) the ability of males to locate, track and mate with females. The three concentrations of the water-soluble fraction of diesel oil (WSF) significantly and non-significantly affect female and male swimming velocities, respectively. In contrast, both the complexity of male and female swimming paths significantly decreased with increasing WSF concentrations, hence suggesting a sex-specific sensitivity to WSF contaminated seawater. In addition, the three WSF concentrations impacted both T. longicornis mating behavior and mating success. Specifically, the ability of males to detect female pheromone trails, to accurately follow trails and to successfully track a female significantly decreased with increasing WSF concentrations. This led to a significant decrease in contact and capture rates from control to WSF contaminated seawater. These results indicate that hydrocarbon contamination of seawater decreases the ability of male copepods to detect and track a female, hence suggest an overall impact on population fitness and dynamics. PMID- 22053188 TI - TCRep 3D: an automated in silico approach to study the structural properties of TCR repertoires. AB - TCRep 3D is an automated systematic approach for TCR-peptide-MHC class I structure prediction, based on homology and ab initio modeling. It has been considerably generalized from former studies to be applicable to large repertoires of TCR. First, the location of the complementary determining regions of the target sequences are automatically identified by a sequence alignment strategy against a database of TCR Valpha and Vbeta chains. A structure-based alignment ensures automated identification of CDR3 loops. The CDR are then modeled in the environment of the complex, in an ab initio approach based on a simulated annealing protocol. During this step, dihedral restraints are applied to drive the CDR1 and CDR2 loops towards their canonical conformations, described by Al-Lazikani et. al. We developed a new automated algorithm that determines additional restraints to iteratively converge towards TCR conformations making frequent hydrogen bonds with the pMHC. We demonstrated that our approach outperforms popular scoring methods (Anolea, Dope and Modeller) in predicting relevant CDR conformations. Finally, this modeling approach has been successfully applied to experimentally determined sequences of TCR that recognize the NY-ESO-1 cancer testis antigen. This analysis revealed a mechanism of selection of TCR through the presence of a single conserved amino acid in all CDR3beta sequences. The important structural modifications predicted in silico and the associated dramatic loss of experimental binding affinity upon mutation of this amino acid show the good correspondence between the predicted structures and their biological activities. To our knowledge, this is the first systematic approach that was developed for large TCR repertoire structural modeling. PMID- 22053189 TI - Crystal structure of thrombin in complex with S-variegin: insights of a novel mechanism of inhibition and design of tunable thrombin inhibitors. AB - The inhibition of thrombin is one of the important treatments of pathological blood clot formation. Variegin, isolated from the tropical bont tick, is a novel molecule exhibiting a unique 'two-modes' inhibitory property on thrombin active site (competitive before cleavage, noncompetitive after cleavage). For the better understanding of its function, we have determined the crystal structure of the human alpha-thrombin:synthetic-variegin complex at 2.4 A resolution. The structure reveals a new mechanism of thrombin inhibition by disrupting the charge relay system. Based on the structure, we have designed 17 variegin variants, differing in potency, kinetics and mechanism of inhibition. The most active variant is about 70 times more potent than the FDA-approved peptidic thrombin inhibitor, hirulog-1/bivalirudin. In vivo antithrombotic effects of the variegin variants correlate well with their in vitro affinities for thrombin. Our results encourage that variegin and the variants show strong potential for the development of tunable anticoagulants. PMID- 22053190 TI - The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell. AB - Resveratrol is a major phytoalexin produced by plants in response to various stresses and promotes disease resistance. The resistance of North American grapevine Vitis rupestris is correlated with a hypersensitive reaction (HR), while susceptible European Vitis vinifera cv. 'Pinot Noir' does not exhibit HR, but expresses basal defence. We have shown previously that in cell lines derived from the two Vitis species, the bacterial effector Harpin induced a rapid and sensitive accumulation of stilbene synthase (StSy) transcripts, followed by massive cell death in V. rupestris. In the present work, we analysed the function of the phytoalexin resveratrol, the product of StSy. We found that cv. 'Pinot Noir' accumulated low resveratrol and its glycoside trans-piceid, whereas V. rupestris produced massive trans-resveratrol and the toxic oxidative delta viniferin, indicating that the preferred metabolitism of resveratrol plays role in Vitis resistance. Cellular responses to resveratrol included rapid alkalinisation, accumulation of pathogenesis-related protein 5 (PR5) transcripts, oxidative burst, actin bundling, and cell death. Microtubule disruption and induction of StSy were triggered by Harpin, but not by resveratrol. Whereas most responses proceeded with different amplitude for the two cell lines, the accumulation of resveratrol, and the competence for resveratrol-induced oxidative burst differed in quality. The data lead to a model, where resveratrol, in addition to its classical role as antimicrobial phytoalexin, represents an important regulator for initiation of HR-related cell death. PMID- 22053191 TI - FGF/FGFR signaling coordinates skull development by modulating magnitude of morphological integration: evidence from Apert syndrome mouse models. AB - The fibroblast growth factor and receptor system (FGF/FGFR) mediates cell communication and pattern formation in many tissue types (e.g., osseous, nervous, vascular). In those craniosynostosis syndromes caused by FGFR1-3 mutations, alteration of signaling in the FGF/FGFR system leads to dysmorphology of the skull, brain and limbs, among other organs. Since this molecular pathway is widely expressed throughout head development, we explore whether and how two specific mutations on Fgfr2 causing Apert syndrome in humans affect the pattern and level of integration between the facial skeleton and the neurocranium using inbred Apert syndrome mouse models Fgfr2(+/S252W) and Fgfr2(+/P253R) and their non-mutant littermates at P0. Skull morphological integration (MI), which can reflect developmental interactions among traits by measuring the intensity of statistical associations among them, was assessed using data from microCT images of the skull of Apert syndrome mouse models and 3D geometric morphometric methods. Our results show that mutant Apert syndrome mice share the general pattern of MI with their non-mutant littermates, but the magnitude of integration between and within the facial skeleton and the neurocranium is increased, especially in Fgfr2(+/S252W) mice. This indicates that although Fgfr2 mutations do not disrupt skull MI, FGF/FGFR signaling is a covariance-generating process in skull development that acts as a global factor modulating the intensity of MI. As this pathway evolved early in vertebrate evolution, it may have played a significant role in establishing the patterns of skull MI and coordinating proper skull development. PMID- 22053192 TI - Expression of p53 in the effects of artesunate on induction of apoptosis and inhibition of proliferation in rat primary hepatic stellate cells. AB - BACKGROUND: Activation of hepatic stellate cells (HSCs) plays an important role in the development of cirrhosis through the increased production of collagen. p53, the "guardian of the genome", is a transcription factor that can bind to promoter regions of hundreds of genes where it either activates or suppresses gene expression. Thereby, p53 serves as a tumor suppressor by inducing cell cycle arrest, apoptosis, senescence and DNA repair. Artesunate is a derivative of Artemisinin, Scholars had found it had more extensive pharmacological effects past 10 years. However, little is known about the expression of p53 in the effects of Artesunate on induction of apoptosis and inhibition of proliferation in rat HSCs. METHODOLOGY/PRINCIPAL FINDINGS: Isolated and cultured rat primary HSCs in the flask for 10 days to make cells activated. HSCs were divided into two groups: experimental groups and control groups, experimental groups included with various concentrations of Artesunate (125, 150, 175, 200, 225 umol/L) for 24, 48 and 72 hours. Analysis of MTT revealed that activated HSCs treated with various concentrations of Artesunate (150-225 umol/L) were inhibited on dose and time effect relationships; Concentration of hydroxyproline in supernatant was detected by digestive method; Analysis of flow cytometry demonstrated that Artesunate could arrest cell cycle in G1 and induce apoptosis; The nuclear morphological changes in apoptotic cells were evaluated with DNA staining by Hoechst 33258 dye; The expression of p53 were up-regulated showed by western blotting and RT-PCR. CONCLUSION: Artesunate could inhibit HSCs proliferation in dose-dependent and time-dependent manners in vitro through increase the expression of p53. PMID- 22053193 TI - Impact of manganese, copper and zinc ions on the transcriptome of the nosocomial pathogen Enterococcus faecalis V583. AB - Mechanisms that enable Enterococcus to cope with different environmental stresses and their contribution to the switch from commensalism to pathogenicity of this organism are still poorly understood. Maintenance of intracellular homeostasis of metal ions is crucial for survival of these bacteria. In particular Zn(2+), Mn(2+) and Cu(2+) are very important metal ions as they are co-factors of many enzymes, are involved in oxidative stress defense and have a role in the immune system of the host. Their concentrations inside the human body vary hugely, which makes it imperative for Enterococcus to fine-tune metal ion homeostasis in order to survive inside the host and colonize it. Little is known about metal regulation in Enterococcus faecalis. Here we present the first genome-wide description of gene expression of E. faecalis V583 growing in the presence of high concentrations of zinc, manganese or copper ions. The DNA microarray experiments revealed that mostly transporters are involved in the responses of E. faecalis to prolonged exposure to high metal concentrations although genes involved in cellular processes, in energy and amino acid metabolisms and genes related to the cell envelope also seem to play important roles. PMID- 22053194 TI - Four and a half LIM protein 1C (FHL1C): a binding partner for voltage-gated potassium channel K(v1.5). AB - Four-and-a-half LIM domain protein 1 isoform A (FHL1A) is predominantly expressed in skeletal and cardiac muscle. Mutations in the FHL1 gene are causative for several types of hereditary myopathies including X-linked myopathy with postural muscle atrophy (XMPMA). We here studied myoblasts from XMPMA patients. We found that functional FHL1A protein is completely absent in patient myoblasts. In parallel, expression of FHL1C is either unaffected or increased. Furthermore, a decreased proliferation rate of XMPMA myoblasts compared to controls was observed but an increased number of XMPMA myoblasts was found in the G(0)/G(1) phase. Furthermore, low expression of K(v1.5), a voltage-gated potassium channel known to alter myoblast proliferation during the G(1) phase and to control repolarization of action potential, was detected. In order to substantiate a possible relation between K(v1.5) and FHL1C, a pull-down assay was performed. A physical and direct interaction of both proteins was observed in vitro. In addition, confocal microscopy revealed substantial colocalization of FHL1C and K(v1.5) within atrial cells, supporting a possible interaction between both proteins in vivo. Two-electrode voltage clamp experiments demonstrated that coexpression of K(v1.5) with FHL1C in Xenopus laevis oocytes markedly reduced K(+) currents when compared to oocytes expressing K(v1.5) only. We here present the first evidence on a biological relevance of FHL1C. PMID- 22053195 TI - A DNA virus of Drosophila. AB - Little is known about the viruses infecting most species. Even in groups as well studied as Drosophila, only a handful of viruses have been well-characterized. A viral metagenomic approach was used to explore viral diversity in 83 wild-caught Drosophila innubila, a mushroom feeding member of the quinaria group. A single fly that was injected with, and died from, Drosophila C Virus (DCV) was added to the sample as a control. Two-thirds of reads in the infected sample had DCV as the best BLAST hit, suggesting that the protocol developed is highly sensitive. In addition to the DCV hits, several sequences had Oryctes rhinoceros Nudivirus, a double-stranded DNA virus, as a best BLAST hit. The virus associated with these sequences was termed Drosophila innubila Nudivirus (DiNV). PCR screens of natural populations showed that DiNV was both common and widespread taxonomically and geographically. Electron microscopy confirms the presence of virions in fly fecal material similar in structure to other described Nudiviruses. In 2 species, D. innubila and D. falleni, the virus is associated with a severe (~80-90%) loss of fecundity and significantly decreased lifespan. PMID- 22053196 TI - Effectiveness of pandemic H1N1-2009 vaccination in reducing laboratory confirmed influenza infections among military recruits in tropical Singapore. AB - BACKGROUND: Limited information is available about pandemic H1N1-2009 influenza vaccine effectiveness in tropical communities. We studied the effectiveness of a pandemic H1N1 vaccination program in reducing influenza cases in Singapore. METHODS: A surveillance study was conducted among military personnel presenting with febrile respiratory illness from mid-2009 to mid-2010. Consenting individuals underwent nasal washes, which were tested with RT-PCR and subtyped. A vaccination program (inactivated monovalent Panvax H1N1-2009 vaccine) was carried out among recruits. A Bayesian hierarchical model was used to quantify relative risks in the pre- and post-vaccination periods. An autoregressive generalised linear model (GLM) was developed to minimise confounding. RESULTS: Of 2858 participants, 437 (15.3%), 60 (2.1%), and 273 (9.6%) had pandemic H1N1, H3N2, and influenza B. The ratio of relative risks for pandemic H1N1 infection before and after vaccination for the recruit camp relative to other camps was 0.14 (0.016,0.49); for H3N2, 0.44 (0.035,1.8); and for influenza B, 18 (0.77,89). Using the GLM for the recruit camp, post-vaccination weekly cases decreased by 54% (37%,67%, p<0.001) from that expected without vaccination; influenza B increased by 66 times (9-479 times, p<0.001); with no statistical difference for H3N2 (p = 0.54). CONCLUSIONS: Pandemic vaccination reduced H1N1-2009 disease burden among military recruits. Routine seasonal influenza vaccination should be considered. PMID- 22053197 TI - Insights into a multidrug resistant Escherichia coli pathogen of the globally disseminated ST131 lineage: genome analysis and virulence mechanisms. AB - Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum beta-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI. PMID- 22053198 TI - Sequential fragmentation of Pleistocene forests in an East Africa biodiversity hotspot: chameleons as a model to track forest history. AB - BACKGROUND: The Eastern Arc Mountains (EAM) is an example of naturally fragmented tropical forests, which contain one of the highest known concentrations of endemic plants and vertebrates. Numerous paleo-climatic studies have not provided direct evidence for ancient presence of Pleistocene forests, particularly in the regions in which savannah presently occurs. Knowledge of the last period when forests connected EAM would provide a sound basis for hypothesis testing of vicariance and dispersal models of speciation. Dated phylogenies have revealed complex patterns throughout EAM, so we investigated divergence times of forest fauna on four montane isolates in close proximity to determine whether forest break-up was most likely to have been simultaneous or sequential, using population genetics of a forest restricted arboreal chameleon, Kinyongia boehmei. METHODOLOGY/PRINCIPAL FINDINGS: We used mitochondrial and nuclear genetic sequence data and mutation rates from a fossil-calibrated phylogeny to estimate divergence times between montane isolates using a coalescent approach. We found that chameleons on all mountains are most likely to have diverged sequentially within the Pleistocene from 0.93-0.59 Ma (95% HPD 0.22-1.84 Ma). In addition, post-hoc tests on chameleons on the largest montane isolate suggest a population expansion ~182 Ka. CONCLUSIONS/SIGNIFICANCE: Sequential divergence is most likely to have occurred after the last of three wet periods within the arid Plio Pleistocene era, but was not correlated with inter-montane distance. We speculate that forest connection persisted due to riparian corridors regardless of proximity, highlighting their importance in the region's historic dispersal events. The population expansion coincides with nearby volcanic activity, which may also explain the relative paucity of the Taita's endemic fauna. Our study shows that forest chameleons are an apposite group to track forest fragmentation, with the inference that forest extended between some EAM during the Pleistocene 1.1-0.9 Ma. PMID- 22053199 TI - Integrating stomach content and stable isotope analyses to quantify the diets of pygoscelid penguins. AB - Stomach content analysis (SCA) and more recently stable isotope analysis (SIA) integrated with isotopic mixing models have become common methods for dietary studies and provide insight into the foraging ecology of seabirds. However, both methods have drawbacks and biases that may result in difficulties in quantifying inter-annual and species-specific differences in diets. We used these two methods to simultaneously quantify the chick-rearing diet of Chinstrap (Pygoscelis antarctica) and Gentoo (P. papua) penguins and highlight methods of integrating SCA data to increase accuracy of diet composition estimates using SIA. SCA biomass estimates were highly variable and underestimated the importance of soft bodied prey such as fish. Two-source, isotopic mixing model predictions were less variable and identified inter-annual and species-specific differences in the relative amounts of fish and krill in penguin diets not readily apparent using SCA. In contrast, multi-source isotopic mixing models had difficulty estimating the dietary contribution of fish species occupying similar trophic levels without refinement using SCA-derived otolith data. Overall, our ability to track inter annual and species-specific differences in penguin diets using SIA was enhanced by integrating SCA data to isotopic mixing modes in three ways: 1) selecting appropriate prey sources, 2) weighting combinations of isotopically similar prey in two-source mixing models and 3) refining predicted contributions of isotopically similar prey in multi-source models. PMID- 22053200 TI - Degree of landscape fragmentation influences genetic isolation among populations of a gliding mammal. AB - Forests and woodlands are under continuing pressure from urban and agricultural development. Tree-dependent mammals that rarely venture to the ground are likely to be highly sensitive to forest fragmentation. The Australian squirrel glider (Petaurus norfolcensis) provides an excellent case study to examine genetic (functional) connectivity among populations. It has an extensive range that occurs in a wide band along the east coast. However, its forest and woodland habitat has become greatly reduced in area and is severely fragmented within the southern inland part of the species' range, where it is recognised as threatened. Within central and northern coastal regions, habitat is much more intact and we thus hypothesise that genetic connectivity will be greater in this region than in the south. To test this we employed microsatellite analysis in a molecular population biology approach. Most sampling locations in the highly modified south showed signatures of genetic isolation. In contrast, a high level of genetic connectivity was inferred among most sampled populations in the more intact habitat of the coastal region, with samples collected 1400 km apart having similar genetic cluster membership. Nonetheless, some coastal populations associated with urbanisation and agriculture are genetically isolated, suggesting the historic pattern observed in the south is emerging on the coast. Our study demonstrates that massive landscape changes following European settlement have had substantial impacts on levels of connectivity among squirrel glider populations, as predicted on the basis of the species' ecology. This suggests that landscape planning and management in the south should be focused on restoring habitat connectivity where feasible, while along the coast, existing habitat connectivity must be maintained and recent losses restored. Molecular population biology approaches provide a ready means for identifying fragmentation effects on a species at multiple scales. Such studies are required to examine the generality of our findings for other tree-dependent species. PMID- 22053201 TI - The response of Thalassiosira pseudonana to long-term exposure to increased CO2 and decreased pH. AB - The effect of ocean acidification conditions has been investigated in cultures of the diatom Thalassiosira pseudonana CCMP1335. Expected end-of-the-century pCO(2) (aq) concentrations of 760 uatm (equivalent to pH 7.8) were compared with present day condition (380 uatm CO(2), pH 8.1). Batch culture pH changed rapidly because of CO(2) (aq) assimilation and pH targets of 7.8 and 8.1 could not be sustained. Long-term (~100 generation) pH-auxostat, continuous cultures could be maintained at target pH when cell density was kept low (<2*10(5) cells mL(-1)). After 3 months continuous culture, the C:N ratio was slightly decreased under high CO(2) conditions and red fluorescence per cell was slightly increased. However, no change was detected in photosynthetic efficiency (F(v)/F(m)) or functional cross section of PS II (sigma(PSII)). Elevated pCO(2) has been predicted to be beneficial to diatoms due to reduced cost of carbon concentration mechanisms. There was reduced transcription of one putative delta-carbonic anhydrase (CA-4) after 3 months growth at increased CO(2) but 3 other delta-CAs and the small subunit of RUBISCO showed no change. There was no evidence of adaptation or clade selection of T. pseudonana after ~100 generations at elevated CO(2). On the basis of this long-term culture, pH change of this magnitude in the future ocean may have little effect on T. pseudonana in the absence of genetic adaption. PMID- 22053202 TI - Scaling of brain metabolism and blood flow in relation to capillary and neural scaling. AB - Brain is one of the most energy demanding organs in mammals, and its total metabolic rate scales with brain volume raised to a power of around 5/6. This value is significantly higher than the more common exponent 3/4 relating whole body resting metabolism with body mass and several other physiological variables in animals and plants. This article investigates the reasons for brain allometric distinction on a level of its microvessels. Based on collected empirical data it is found that regional cerebral blood flow CBF across gray matter scales with cortical volume V as CBF ~ V(-1/6), brain capillary diameter increases as V(1/12), and density of capillary length decreases as V(-1/6). It is predicted that velocity of capillary blood is almost invariant (~V(epsilon)), capillary transit time scales as V(1/6), capillary length increases as V(1/6+epsilon), and capillary number as V(2/3-epsilon), where epsilon is typically a small correction for medium and large brains, due to blood viscosity dependence on capillary radius. It is shown that the amount of capillary length and blood flow per cortical neuron are essentially conserved across mammals. These results indicate that geometry and dynamics of global neuro-vascular coupling have a proportionate character. Moreover, cerebral metabolic, hemodynamic, and microvascular variables scale with allometric exponents that are simple multiples of 1/6, rather than 1/4, which suggests that brain metabolism is more similar to the metabolism of aerobic than resting body. Relation of these findings to brain functional imaging studies involving the link between cerebral metabolism and blood flow is also discussed. PMID- 22053203 TI - Halofuginone has anti-proliferative effects in acute promyelocytic leukemia by modulating the transforming growth factor beta signaling pathway. AB - Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARalpha) expression in acute promyelocytic leukemia (APL) impairs transforming growth factor beta (TGFbeta) signaling, leading to cell growth advantage. Halofuginone (HF), a low molecular-weight alkaloid that modulates TGFbeta signaling, was used to treat APL cell lines and non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice subjected to transplantation with leukemic cells from human chorionic gonadotrophin-PML-RARalpha transgenic mice (TG). Cell cycle analysis using incorporated bromodeoxyuridine and 7-amino-actinomycin D showed that, in NB4 and NB4-R2 APL cell lines, HF inhibited cellular proliferation (P<0.001) and induced apoptosis (P = 0.002) after a 24-hour incubation. Addition of TGFbeta revealed that NB4 cells were resistant to its growth-suppressive effects and that HF induced these effects in the presence or absence of the cytokine. Cell growth inhibition was associated with up-regulation of TGFbeta target genes involved in cell cycle regulation (TGFB, TGFBRI, SMAD3, p15, and p21) and down-regulation of MYC. Additionally, TGFbeta protein levels were decreased in leukemic TG animals and HF in vivo could restore TGFbeta values to normal. To test the in vivo anti leukemic activity of HF, we transplanted NOD/SCID mice with TG leukemic cells and treated them with HF for 21 days. HF induced partial hematological remission in the peripheral blood, bone marrow, and spleen. Together, these results suggest that HF has anti-proliferative and anti-leukemic effects by reversing the TGFbeta blockade in APL. Since loss of the TGFbeta response in leukemic cells may be an important second oncogenic hit, modulation of TGFbeta signaling may be of therapeutic interest. PMID- 22053204 TI - TIMP3 regulates mammary epithelial apoptosis with immune cell recruitment through differential TNF dependence. AB - Post-lactation mammary involution is a homeostatic process requiring epithelial apoptosis and clearance. Given that the deficiency of the extracellular metalloproteinase inhibitor TIMP3 impacts epithelial apoptosis and heightens inflammatory response, we investigated whether TIMP3 regulates these distinct processes during the phases of mammary gland involution in the mouse. Here we show that TIMP3 deficiency leads to TNF dysregulation, earlier caspase activation and onset of mitochondrial apoptosis. This accelerated first phase of involution includes faster loss of initiating signals (STAT3 activation; TGFbeta3) concurrent with immediate luminal deconstruction through E-cadherin fragmentation. Epithelial apoptosis is followed by accelerated adipogenesis and a greater macrophage and T-cell infiltration in Timp3(-/-) involuting glands. Crossing in Tnf deficiency abrogates caspase 3 activation, but heightens macrophage and T-cell influx into Timp3(-/-) glands. The data indicate that TIMP3 differentially impacts apoptosis and inflammatory cell influx, based on involvement of TNF, during the process of mammary involution. An understanding of the molecular factors and wound healing microenvironment of the postpartum mammary gland may have implications for understanding pregnancy-associated breast cancer risk. PMID- 22053205 TI - A statistical framework for the interpretation of mtDNA mixtures: forensic and medical applications. AB - BACKGROUND: Mitochondrial DNA (mtDNA) variation is commonly analyzed in a wide range of different biomedical applications. Cases where more than one individual contribute to a stain genotyped from some biological material give rise to a mixture. Most forensic mixture cases are analyzed using autosomal markers. In rape cases, Y-chromosome markers typically add useful information. However, there are important cases where autosomal and Y-chromosome markers fail to provide useful profiles. In some instances, usually involving small amounts or degraded DNA, mtDNA may be the only useful genetic evidence available. Mitochondrial DNA mixtures also arise in studies dealing with the role of mtDNA variation in tumorigenesis. Such mixtures may be generated by the tumor, but they could also originate in vitro due to inadvertent contamination or a sample mix-up. METHODS/PRINCIPAL FINDINGS: We present the statistical methods needed for mixture interpretation and emphasize the modifications required for the more well-known methods based on conventional markers to generalize to mtDNA mixtures. Two scenarios are considered. Firstly, only categorical mtDNA data is assumed available, that is, the variants contributing to the mixture. Secondly, quantitative data (peak heights or areas) on the allelic variants are also accessible. In cases where quantitative information is available in addition to allele designation, it is possible to extract more precise information by using regression models. More precisely, using quantitative information may lead to a unique solution in cases where the qualitative approach points to several possibilities. Importantly, these methods also apply to clinical cases where contamination is a potential alternative explanation for the data. CONCLUSIONS/SIGNIFICANCE: We argue that clinical and forensic scientists should give greater consideration to mtDNA for mixture interpretation. The results and examples show that the analysis of mtDNA mixtures contributes substantially to forensic casework and may also clarify erroneous claims made in clinical genetics regarding tumorigenesis. PMID- 22053206 TI - Diabetes mellitus and its correlates in an Iranian adult population. AB - The rising epidemic of diabetes imposes a substantial economic burden on the Middle East. Using baseline data from a population based cohort study, we aimed to identify the correlates of diabetes mellitus (DM) in a mainly rural population from Iran. Between 2004 and 2007, 50044 adults between 30 and 87 years old from Golestan Province located in Northeast Iran were enrolled in the Golestan Cohort Study. Demographic and health-related information was collected using questionnaires. Individuals' body sizes at ages 15 and 30 were assessed by validated pictograms ranging from 1 (very lean) to 7 in men and 9 in women. DM diagnosis was based on the self-report of a physician's diagnosis. The accuracy of self-reported DM was evaluated in a subcohort of 3811 individuals using fasting plasma glucose level and medical records. Poisson regression with robust variance estimator was used to estimate prevalence ratios (PR's). The prevalence of self-reported DM standardized to the national and world population was 5.7% and 6.2%, respectively. Self-reported DM had 61.5% sensitivity and 97.6% specificity. Socioeconomic status was inversely associated with DM prevalence. Green tea and opium consumption increased the prevalence of DM. Obesity at all ages and extreme leanness in childhood increased diabetes prevalence. Being obese throughout life doubled DM prevalence in women (PR: 2.1; 95% CI: 1.8, 2.4). These findings emphasize the importance of improving DM awareness, improving general living conditions, and early lifestyle modifications in diabetes prevention. PMID- 22053207 TI - Activating transcription factor 3 deficiency promotes cardiac hypertrophy, dysfunction, and fibrosis induced by pressure overload. AB - Activating transcription factor 3 (ATF3), which is encoded by an adaptive response gene induced by various stimuli, plays an important role in the cardiovascular system. However, the effect of ATF3 on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of ATF3 deficiency on cardiac hypertrophy using in vitro and in vivo models. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements and by pathological and molecular analysis. ATF3 deficiency promoted cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared to the wild type (WT) mice. Furthermore, enhanced activation of the MEK-ERK1/2 and JNK pathways was found in ATF3-knockout (KO) mice compared to WT mice. In vitro studies performed in cultured neonatal mouse cardiomyocytes confirmed that ATF3 deficiency promotes cardiomyocyte hypertrophy induced by angiotensin II, which was associated with the amplification of MEK-ERK1/2 and JNK signaling. Our results suggested that ATF3 plays a crucial role in the development of cardiac hypertrophy via negative regulation of the MEK-ERK1/2 and JNK pathways. PMID- 22053208 TI - Protective effect of hepatitis B vaccine combined with two-dose hepatitis B immunoglobulin on infants born to HBsAg-positive mothers. AB - BACKGROUND: Despite the use of hepatitis B (HB) vaccine and hepatitis B immunoglobulin (HBIG), a portion of infants are still non- or low-responders, or even immunoprophylaxis failure. We aimed to determine the immune response in the infants from the mothers being positive for hepatitis B surface antigen (HBsAg), by which the infants received three doses of HB vaccine in combination with two dose 200 IU HBIG injections. METHODS: In this retrospective study, 621 infants from HBsAg-positive mothers in Beijing YouAn Hospital between January 2008 and December 2009 were included. All the infants were given three doses of 10 ug HB vaccine (at 0, 1 and 6 months of age) and two-dose of 200 IU HBIG (at birth and in 2 weeks of age). Serum HBsAg and antibody to HBsAg (anti-HBs) in all the infants were determined at 7 months of age. RESULTS: Of the 621 infants, 2.9% were immunoprophylaxis failure (positive for HBsAg), 1.4% were non-responders (anti-HBs undetectable), 95.7% were responders. The 594 responders could be categorized into three subsets, 22 were 10 to 99 IU/L for anti-HBs levels, 191 were 100 to 999 IU/L, and 381 were >=1000 IU/L. The immunoprophylaxis failure rate was at 0% and 5.2% for the infants of HBeAg-negative and HBeAg-positive mothers(P<0.001). Infants from mothers with detectable HBV DNA had higher incidence of immunoprophylaxis failure than those of mothers without detectable HBV DNA (P = 0.002). The factors including gender, birth weight, gestation weeks, the rates of maternal HBeAg-positive, and detectable HBV DNA did not contribute to the no response to HB vaccination. CONCLUSIONS: Through vaccination by three doses of HB and two-dose of HBIG, majority of the infants (95.7%) achieved a protective level of anti-HBs at 7 months of age. Maternal HBeAg-positive and HBV DNA detectable were associated with the immunoprophylaxis failure, but not contribute to the non- or low-response to HB vaccination. PMID- 22053209 TI - Cluster K mycobacteriophages: insights into the evolutionary origins of mycobacteriophage TM4. AB - Five newly isolated mycobacteriophages--Angelica, CrimD, Adephagia, Anaya, and Pixie--have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence similarities warrant grouping these into Cluster K, with subdivision into three subclusters: K1, K2, and K3. Although the overall genome architectures of these phages are similar, TM4 appears to have lost at least two segments of its genome, a central region containing the integration apparatus, and a segment at the right end. This suggests that TM4 is a recent derivative of a temperate parent, resolving a long-standing conundrum about its biology, in that it was reportedly recovered from a lysogenic strain of Mycobacterium avium, but it is not capable of forming lysogens in any mycobacterial host. Like TM4, all of the Cluster K phages infect both fast- and slow-growing mycobacteria, and all of them -with the exception of TM4--form stable lysogens in both Mycobacterium smegmatis and Mycobacterium tuberculosis; immunity assays show that all five of these phages share the same immune specificity. TM4 infects these lysogens suggesting that it was either derived from a heteroimmune temperate parent or that it has acquired a virulent phenotype. We have also characterized a widely-used conditionally replicating derivative of TM4 and identified mutations conferring the temperature-sensitive phenotype. All of the Cluster K phages contain a series of well conserved 13 bp repeats associated with the translation initiation sites of a subset of the genes; approximately one half of these contain an additional sequence feature composed of imperfectly conserved 17 bp inverted repeats separated by a variable spacer. The K1 phages integrate into the host tmRNA and the Cluster K phages represent potential new tools for the genetics of M. tuberculosis and related species. PMID- 22053210 TI - The phytoplankton Nannochloropsis oculata enhances the ability of Roseobacter clade bacteria to inhibit the growth of fish pathogen Vibrio anguillarum. AB - BACKGROUND: Phytoplankton cultures are widely used in aquaculture for a variety of applications, especially as feed for fish larvae. Phytoplankton cultures are usually grown in outdoor tanks using natural seawater and contain probiotic or potentially pathogenic bacteria. Some Roseobacter clade isolates suppress growth of the fish pathogen Vibrio anguillarum. However, most published information concerns interactions between probiotic and pathogenic bacteria, and little information is available regarding the importance of phytoplankton in these interactions. The objectives of this study, therefore, were to identify probiotic Roseobacter clade members in phytoplankton cultures used for rearing fish larvae and to investigate their inhibitory activity towards bacterial fish pathogens in the presence of the phytoplankton Nannochloropsis oculata. METHODOLOGY/PRINCIPAL FINDINGS: The fish pathogen V. anguillarum, was challenged with 6 Roseobacter clade isolates (Sulfitobacter sp. (2 strains), Thalassobius sp., Stappia sp., Rhodobacter sp., and Antarctobacter sp.) from phytoplankton cultures under 3 different nutritional conditions. In an organic nutrient-rich medium (VNSS), 6 Roseobacter clade isolates, as well as V. anguillarum, grew well (10(9) CFU/ml), even when cocultured. In contrast, in a phytoplankton culture medium (ESM) based on artificial seawater, coculture with the 6 isolates decreased the viability of V. anguillarum by approximately more than 10-fold. Excreted substances in media conditioned by growth of the phytoplankton N. oculata (NCF medium) resulted in the complete eradication of V. anguillarum when cocultured with the roseobacters. Autoclaved NCF had the same inhibitory effect. Furthermore, Sulfitobacter sp. much more efficiently incorporated (14)C- photosynthetic metabolites ((14)C-EPM) excreted by N. oculata than did V. anguillarum. CONCLUSION/SIGNIFICANCE: Cocultures of a phytoplankton species and Roseobacter clade members exhibited a greater antibacterial effect against an important fish pathogen (V. anguillarum) than roseobacters alone. Thus, cooperation of N. oculata, and perhaps other phytoplankton species, with certain roseobacters might provide a powerful tool for eliminating fish pathogens from fish-rearing tanks. PMID- 22053211 TI - High prevalence of systemic autoimmune diseases in patients with Meniere's disease. AB - BACKGROUND: Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL). METHODS AND FINDINGS: We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFalpha, INFgamma). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. CONCLUSIONS: Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD. PMID- 22053212 TI - Vaccination of lactating dairy cows for the prevention of aflatoxin B1 carry over in milk. AB - The potential of anaflatoxin B(1) (AnAFB(1)) conjugated to keyhole limpet hemocyanin (KLH) as a vaccine (AnAFB(1)-KLH) in controlling the carry over of the aflatoxin B(1) (AFB(1)) metabolite aflatoxin M(1) (AFM(1)) in cow milk is reported. AFB(1) is the most carcinogenic compound in food and foodstuffs amongst aflatoxins (AFs). AnAFB(1) is AFB(1) chemically modified as AFB(1)-1(O carboxymethyl) oxime. In comparison to AFB(1), AnAFB(1) has proven to be non toxic in vitro to human hepatocarcinoma cells and non mutagenic to Salmonella typhimurium strains. AnAFB(1)-KLH was used for immunization of cows proving to induce a long lasting titer of anti-AFB(1) IgG antibodies (Abs) which were cross reactive with AFB(1), AFG(1), and AFG(2). The elicited anti-AFB(1) Abs were able to hinder the secretion of AFM(1) into the milk of cows continuously fed with AFB(1). Vaccination of lactating animals with conjugated AnAFB(1) may represent a solution to the public hazard constituted by milk and cheese contaminated with AFs. PMID- 22053213 TI - DeltaNp63alpha-mediated induction of epidermal growth factor receptor promotes pancreatic cancer cell growth and chemoresistance. AB - Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to current chemotherapy regimens, in part due to alterations in the p53 tumor suppressor pathway. p53 homolog p63 is a transcription factor essential for the development and differentiation of epithelial surfaces. However its function in cancer is controversial and its role in PDAC is not known. We discovered that DeltaNp63alpha was the predominantly expressed p63 variant in pancreatic cancer cell lines. DeltaNp63alpha protein and mRNA levels were high in T3M4, BxPC3 and COLO-357 pancreatic cancer cells and low in ASPC-1 and PANC-1 cells. Overexpression of DeltaNp63alpha in PANC-1 cells and shRNA-mediated knockdown in T3M4 cells indicated that DeltaNp63alpha promoted anchorage-dependent and independent growth, motility and invasion, and enhanced resistance to cisplatin induced apoptosis. Epidermal growth factor receptor (EGFR) signaling pathways contribute to the biological aggressiveness of PDAC, and we found that the motogenic effects of DeltaNp63alpha were augmented in presence of EGF. Ectopic expression of DeltaNp63alpha resulted in upregulation of EGFR and beta1-integrin in PANC-1 cells. Conversely, DeltaNp63alpha knockdown had an opposite effect in T3M4 cells. DeltaNp63alpha potentiated EGF-mediated activation of ERK, Akt and JNK signaling. Chromatin immunoprecipitation and functional reporter assays demonstrated that DeltaNp63alpha activated EGFR transcription. 14-3-3sigma transcription was also positively regulated by DeltaNp63alpha and we have previously shown that 14-3-3sigma contributes to chemoresistance in pancreatic cancer cell lines. Conversely, shRNA-mediated knockdown of 14-3-3sigma led to abrogation of the DeltaNp63alpha effects on cell proliferation and invasion. Thus, p53 homolog DeltaNp63alpha enhances the oncogenic potential of pancreatic cancer cells through trans-activation of EGFR and 14-3-3sigma. PMID- 22053214 TI - The FSHD atrophic myotube phenotype is caused by DUX4 expression. AB - BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is linked to deletions in 4q35 within the D4Z4 repeat array in which we identified the double homeobox 4 (DUX4) gene. We found stable DUX4 mRNAs only derived from the most distal D4Z4 unit and unexpectedly extended to the flanking pLAM region that provided an intron and a polyadenylation signal. DUX4 encodes a transcription factor expressed in FSHD but not control primary myoblasts or muscle biopsies. The DUX4 protein initiates a large transcription deregulation cascade leading to muscle atrophy and oxidative stress, which are FSHD key features. METHODOLOGY/PRINCIPAL FINDINGS: We now show that transfection of myoblasts with a DUX4 expression vector leads to atrophic myotube formation associated with the induction of E3 ubiquitin ligases (MuRF1 and Atrogin1/MAFbx) typical of muscle atrophy. DUX4 induces expression of downstream targets deregulated in FSHD such as mu crystallin and TP53. We developed specific siRNAs and antisense oligonucleotides (AOs) targeting the DUX4 mRNA. Addition of these antisense agents to primary FSHD myoblast cultures suppressed DUX4 protein expression and affected expression of the above-mentioned markers. CONCLUSIONS/SIGNIFICANCE: These results constitute a proof of concept for the development of therapeutic approaches for FSHD targeting DUX4 expression. PMID- 22053215 TI - Phosphoinositide 3-kinasegamma controls the intracellular localization of CpG to limit DNA-PKcs-dependent IL-10 production in macrophages. AB - Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG) stimulate innate immune responses. Phosphoinositide 3-kinase (PI3K) has been implicated in CpG-induced immune activation; however, its precise role has not yet been clarified. CpG-induced production of IL-10 was dramatically increased in macrophages deficient in PI3Kgamma (p110gamma(-/-)). By contrast, LPS-induced production of IL-10 was unchanged in the cells. CpG-induced, but not LPS-induced, IL-10 production was almost completely abolished in SCID mice having mutations in DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Furthermore, wortmannin, an inhibitor of DNA-PKcs, completely inhibited CpG-induced IL-10 production, both in wild type and p110gamma(-/-) cells. Microscopic analyses revealed that CpG preferentially localized with DNA-PKcs in p110gamma(-/-) cells than in wild type cells. In addition, CpG was preferentially co-localized with the acidic lysosomal marker, LysoTracker, in p110gamma(-/-) cells, and with an early endosome marker, EEA1, in wild type cells. Over-expression of p110gamma in Cos7 cells resulted in decreased acidification of CpG containing endosome. A similar effect was reproduced using kinase-dead mutants, but not with a ras binding site mutant, of p110gamma. Thus, it is likely that p110gamma, in a manner independent of its kinase activity, inhibits the acidification of CpG-containing endosomes. It is considered that increased acidification of CpG-containing endosomes in p110gamma(-/-) cells enforces endosomal escape of CpG, which results in increased association of CpG with DNA-PKcs to up-regulate IL-10 production in macrophages. PMID- 22053216 TI - Temporal processing of vibratory communication signals at the level of ascending interneurons in Nezara viridula (Hemiptera: Pentatomidae). AB - During mating, males and females of N. viridula (Heteroptera: Pentatomidae) produce sex- and species-specific calling and courtship substrate-borne vibratory signals, grouped into songs. Recognition and localization of these signals are fundamental for successful mating. The recognition is mainly based on the temporal pattern, i.e. the amplitude modulation, while the frequency spectrum of the signals usually only plays a minor role. We examined the temporal selectivity for vibratory signals in four types of ascending vibratory interneurons in N. viridula. Using intracellular recording and labelling technique, we analyzed the neurons' responses to 30 pulse duration/interval duration (PD/ID) combinations. Two response arrays were created for each neuron type, showing the intensity of the responses either as time-averaged spike counts or as peak instantaneous spike rates. The mean spike rate response arrays showed preference of the neurons for short PDs (below 600 ms) and no selectivity towards interval duration; while the peak spike rate response arrays exhibited either short PD/long ID selectivity or no selectivity at all. The long PD/short ID combinations elicited the weakest responses in all neurons tested. No response arrays showed the receiver preference for either constant period or duty cycle. The vibratory song pattern selectivity matched the PD of N. viridula male vibratory signals, thus pointing to temporal filtering for the conspecific vibratory signals already at level of the ascending interneurons. In some neurons the responses elicited by the vibratory stimuli were followed by distinct, regular oscillations of the membrane potential. The distance between the oscillation peaks matched the temporal structure of the male calling song, indicating a possible resonance based mechanism for signal recognition. PMID- 22053217 TI - Detection of genetically altered copper levels in Drosophila tissues by synchrotron x-ray fluorescence microscopy. AB - Tissue-specific manipulation of known copper transport genes in Drosophila tissues results in phenotypes that are presumably due to an alteration in copper levels in the targeted cells. However direct confirmation of this has to date been technically challenging. Measures of cellular copper content such as expression levels of copper-responsive genes or cuproenzyme activity levels, while useful, are indirect. First-generation copper-sensitive fluorophores show promise but currently lack the sensitivity required to detect subtle changes in copper levels. Moreover such techniques do not provide information regarding other relevant biometals such as zinc or iron. Traditional techniques for measuring elemental composition such as inductively coupled plasma mass spectroscopy are not sensitive enough for use with the small tissue amounts available in Drosophila research. Here we present synchrotron x-ray fluorescence microscopy analysis of two different Drosophila tissues, the larval wing imaginal disc, and sectioned adult fly heads and show that this technique can be used to detect changes in tissue copper levels caused by targeted manipulation of known copper homeostasis genes. PMID- 22053218 TI - Loss of zebrafish lgi1b leads to hydrocephalus and sensitization to pentylenetetrazol induced seizure-like behavior. AB - Mutations in the LGI1 gene predispose to a hereditary epilepsy syndrome and is the first gene associated with this disease which does not encode an ion channel protein. In zebrafish, there are two paralogs of the LGI1 gene, lgi1a and lgi1b. Knockdown of lgi1a results in a seizure-like hyperactivity phenotype with associated developmental abnormalities characterized by cellular loss in the eyes and brain. We have now generated knockdown morphants for the lgi1b gene which also show developmental abnormalities but do not show a seizure-like behavior. Instead, the most striking phenotype involves significant enlargement of the ventricles (hydrocephalus). As shown for the lgi1a morphants, however, lgi1b morphants are also sensitized to PTZ-induced hyperactivity. The different phenotypes between the two lgi1 morphants support a subfunctionalization model for the two paralogs. PMID- 22053219 TI - Percutaneous treatment in acute coronary syndromes. AB - Both ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndromes (ACS) are the result of an acute thrombotic lesion obstructing blood flow in the coronary vasculature. Percutaneous treatment has shown to improve clinical outcome in this clinical setting by resolving coronary obstruction with different devices directed to restore coronary blood flow. In comparison with balloon alone angioplasty, implantation of bare metal stents reduced the rate of restenosis and cardiac events, but high rates of restenosis remained, leading to further investigations to develop drug-eluting stents with different pharmacological coatings that reduced restenosis rates and clinical events. In this review, we discuss the current treatment of ACS, reviewing recent randomized clinical trials and advances in medical treatment, including new antiplatelet agents and recent guideline recommendations. PMID- 22053220 TI - Assessment of right ventricular afterload by pressure waveform analysis in acute pulmonary hypertension. AB - AIM: To characterize hydraulic right ventricle (RV) afterload by pulmonary arterial pressure waveform analysis in an acute pulmonary hypertension (PH) model. METHODS: Pulmonary artery (PA) flow and pressure were recorded in six anesthetized sheep. Acute isobaric PH was induced by phenylephrine (active) and PA mechanical constriction (passive). We estimated the amplitude of the forward and reflected pressure waves according to the inflection point. In most cases the inflection pressure was smooth, thus the inflection point was defined as the time at which the first derivative of pulmonary arterial pressure reached its first minimum. We calculated the input and characteristic (Z(C), time-domain Li method) impedances, the capacitance index (stroke volume/pulse pressure), the augmentation index (AI) (reflected pressure/pulse pressure), the fractional pulse pressure (pulse pressure/mean pressure) and the wasted energy generated by the RV due to wave reflection during ejection (E(W)). RESULTS: Pulse pressure, fractional pulse pressure, AI and Z(C) increased and capacitance index decreased during passive PH with respect to control (P < 0.05). In contrast, Z(C) and the capacitance index did not change and E(W) and the AI decreased during active PH. Pulse pressure correlated with E(W) and Z(C) and the AI was correlated with E(W) (r > 0.6, P < 0.05). CONCLUSION: PA pressure waveform analysis allows the quantification of the dynamic RV afterload. Prospective clinical studies will be necessary to validate this time-domain approach to evaluate the dynamic RV afterload in chronic PH. PMID- 22053221 TI - Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough: A meta analysis. AB - AIM: To evaluate the association between genetic polymorphisms and angiotensin converting enzyme inhibitor (ACEI)-related cough, and the race- or ethnicity related difference in the prevalence of cough attributed to ACEI therapy. METHODS: We conducted a search in PubMed, EMBASE, Cinahl, and the Cochrane Database without language limitation. A database of 11 studies on ACEI-related cough, with detailed information regarding ACE I/D or bradykinin B(2) receptor polymorphisms, was created. Eligible studies were synthesized using meta-analysis methods, including cumulative meta-analysis. A subgroup analysis was also performed using ethnicity. RESULTS: Six studies were included on ACE I/D polymorphism (398 Caucasians, 723 East Asians), and three studies were included on bradykinin B(2) receptor polymorphism (300 East Asians). The distribution of ACE genotypes showed significant differences in the entire population (P = 0.004) and in East Asians (P = 0.005) but not in Caucasians (P = 0.23). Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR) = 1.49 (1.11-2.02)]. The meta-analysis with a random effects model showed a significant association between ACE allele I/D and ACEI-related cough [random effects (RE) OR = 1.49 (1.11-2.02), P = 0.009] in East Asians, but not in Caucasians [RE OR = 0.90 (0.60-1.35)]. The allelic frequencies of the bradykinin B(2) receptor gene were significantly different [OR = 2.25 (1.42-3.57)]. The distributions of the T/C genotypes of the bradykinin B(2) receptor gene were significantly different (chi(2) = 8.366, P = 0.015). The meta-analyses revealed that there was a significant association between the bradykinin B(2) receptor allele and ACEI-related cough in East Asians [RE OR = 2.29 (1.42-3.69), P = 0.001]. CONCLUSION: ACE I/D and Bradykinin B(2) receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians, but a negative association between ACE I/D polymorphism and ACEI-related cough was observed in Caucasians. PMID- 22053222 TI - Epicardial coronary artery intimal smooth muscle hyperplasia in a cocaine user. AB - Accelerated epicardial coronary artery atherosclerosis has been well-documented in cocaine users. There are only two reported cases of cocaine-associated diffuse intimal expansion by proliferated smooth muscle cells causing significant coronary luminal compromise. This type of lesion histologically resembled chronic transplant arteriopathy. Here, we report a third such case. PMID- 22053223 TI - Leukoaraiosis on magnetic resonance imaging is related to long-term poor functional outcome after thrombolysis in acute ischemic stroke. AB - OBJECTIVE: Leukoaraiosis (LA) has been suggested to be related to the poor outcome or the occurrence of symptomatic intracerebral hemorrhage (sICH) after acute ischemic stroke. We retrospectively investigated the influences of LA on long-term outcome and the occurrence of sICH after thrombolysis in acute ischemic stroke (AIS). METHODS: In this study, we recruited 164 patients with AIS and magnetic resonance image (MRI)-detected thrombolysis. The presence and extent of LA were assessed using the Fazekas grading system. The National Institutes of Health Stroke Scale score was used to assess the baseline measure of neurologic severity, and the modified Rankin Scale score assessment was used up to 1 year after thrombolysis. RESULTS: Of 164 subjects, 56 (34.2%) showed LA on MRI. Compared to the 108 patients without LA, the patients with LA were of much older age (p<0.01), had a higher prevalence of hypertension (p<0.01), and had a much poorer outcome at 90 days (p=0.05) and 1 yr (p=0.01) after thrombolysis. There were no significant differences in sICH between patients with and without LA on MRI. In univariate analysis for the occurrence of poor outcome at 90 days after thrombolysis, the size of ischemic lesion on diffusion weighted images (DWI), [odds ratio (OR), 1.03; 95% confidence interval (95% CI), 1.01-1.04; p<0.01], recanalization (OR, 0.03; 95% CI, 0.01-0.10; p<0.01), sICH (OR, 12.2; 95% CI, 1.54-95.8), neurologic severity (OR, 1.17; 95% CI, 1.09-1.25; p<0.01), blood glucose level (OR, 1.01; 95% CI, 1.00-1.02; p=0.03), and the presence of LA on MRI (OR, 2.01; 95% CI, 1.04-3.01; p=0.04) were statistically significant. In multivariate analysis, neurologic severity (OR, 1.14; 95% CI, 1.04-1.24; p<0.01), recanalization (OR, 0.03; 95% CI, 0.01-0.11; p<0.01), lesion size on DWI (OR, 1.02; 95% CI, 1.01-1.03; p=0.02), serum glucose level (OR, 1.01; 95% CI; 1.01 1.02; p=0.03), and the presence of LA on MRI (OR, 3.2; 95% CI, 1.22-8.48; p<0.01) showed statistically significant differences. These trends persisted up to 1 yr after thrombolysis. CONCLUSION: In this study, we demonstrated that the presence of LA on MRI might be related to poor outcome after use of intravenous tissue plasminogen activator in AIS. PMID- 22053224 TI - Influence of clinical and anatomic features on treatment decisions for anterior communicating artery aneurysms. AB - OBJECTIVE: The purpose of this study was to analyze the clinical and anatomic features involved in determining treatment modalities for anterior communicating artery (AcoA) aneurysms. METHODS: The authors retrospectively evaluated 112 AcoA aneurysms with pretreatment clinical features including age, Hunt and Hess grade, medical or neurological comorbidity, and anatomical features including aneurysm size, neck size, dome-to-neck ratio, vessel incorporation, multiple lobulation, and morphologic scoring system. Post-treatment clinical results were classified according to the Glasgow Outcome Scale, and anatomic results in coiled patients were classified according to the modified Raymond scale. Using multivariate logistic regression, the probabilities for decision making between surgical clipping and coil embolization were calculated. RESULTS: Sixty-seven patients (60%) were treated with surgical clipping and 45 patients (40%) with endovascular coil embolization. The clinical factor significantly associated with treatment decision was age (>=65 vs. <65 years) and anatomical factors including aneurysm size (small or large vs. medium), dome-to-neck ratio (<2 vs. >=2), presence of vessel incorporation, multiple lobulation, and morphologic score (>=2 vs. <2). In multivariate analysis, older patients (age, >65 years) had significantly higher odds of being treated with coil embolization relative to clipping (adjusted OR=3.78; 95% CI, 1.39-10.3; p=0.0093) and higher morphological score patients (>=2) had a higher tendency toward surgical clipping than endovascular coil embolization (OR=0.23; 95% CI, 0.16-0.93; p=0.0039). CONCLUSION: The optimal decision for treating AcoA aneurysms cannot be determined by any single clinical or anatomic characteristics. All clinical and morphological features need to be considered, and a collaborative neurovascular team approach to AcoA aneurysms is essential. PMID- 22053225 TI - Correlation between Serum D-Dimer Level and Volume in Acute Ischemic Stroke. AB - OBJECTIVE: D-dimer is a breakdown product of fibrin mesh after factor XIII stabilization. Previously, many authors have demonstrated a relationship between D-dimer level and stroke progression or type. This study aimed to investigate the relationship between D-dimer level and stroke volume. METHODS: Between January 2008 and December 2009, we analyzed the D-dimer levels of 59 acute ischemic stroke patients in our neurosurgical department both upon admission and after seven days of initial treatment. Each patient's National Institute of Health Stroke Scale score, modified Rankin Scales score, Glasgow outcome score, and infarction volume were also evaluated. RESULTS: Mean D-dimer level at admission was 626.6 ug/L (range, 77-4,752 ug/L) and the mean level measured after seven days of treatment was 238.3 ug/L (range, 50-924 ug/L). Mean D-dimer level at admission was 215.3 ug/L in patients with focal infarctions, 385.7 ug/L in patients with multiple embolic infarctions, 566.2 ug/L in those with 1-19 cc infarctions, 668.8 ug/L in 20-49 cc infarctions, 702.5 ug/L in 50-199 cc infarctions, and 844.0 ug/L in >200 cc infarctions (p=0.044). On the 7th day of treatment, the D-dimer levels had fallen to 201.0 ug/L, 293.2 ug/L, 272.0 ug/L, 232.8 ug/L, 336.6 ug/L, and 180.0 ug/L, respectively (p=0.530). CONCLUSION: Our study shows that D-dimer level has the positive correlation with infarction volume and can be use to predict infarction-volume. PMID- 22053226 TI - Surgical results of selective median neurotomy for wrist and finger spasticity. AB - OBJECTIVE: This study aimed to evaluate the surgical outcomes of selective median neurotomy (SMN) for spastic wrist and fingers. METHODS: We studied 22 patients with wrist and finger spasticity refractory to optimal oral medication and physical therapy. The authors evaluated spasticity of the wrist and finger muscles by comparing preoperative states with postoperative states using the modified Ashworth scale (MAS). We checked patients for changes in pain according to the visual analog scale (VAS) and degree of satisfaction based on the VAS. RESULTS: The preoperative mean MAS score was 3.27+/-0.46 (mean+/-SD), and mean MAS scores at 3, 6, and 12 months after surgery were 1.82+/-0.5, 1.73+/-0.7, and 1.77+/-0.81 (mean+/-SD), respectively. On the last follow-up visit, the mean MAS score measured 1.64+/-0.9 (mean+/-SD). Wrist and finger spasticity was significantly decreased at 3, 6, and 12 months after the operation (p<0.01). The preoperative mean pain VAS score was 5.85+/-1.07 (mean+/-SD), and the mean pain VAS score on the last follow-up visit after surgery was 2.28+/-1.8 (mean+/-SD). Compared with the preoperative mean pain VAS score, postoperative mean pain VAS score was decreased significantly (p<0.01). On the basis of a VAS ranging from 0 to 100, the mean degree of patient satisfaction was 64.09+/-15.93 (mean+/-SD, range 30-90). CONCLUSION: The authors propose SMN as a possible effective procedure in achieving useful, long-lasting tone and in gaining voluntary movements in spastic wrists and fingers with low morbidity rates. PMID- 22053227 TI - The role of radiosurgery in patients with brain metastasis from small cell lung carcinoma. AB - OBJECTIVE: The purpose of this retrospective study was to evaluate the outcome of gamma knife radiosurgery (GKRS) and/or whole brain radiation therapy (WBRT) for the treatment of small cell lung carcinoma (SCLC) metastasis to the brain. METHODS: From 2000 to 2010, 50 patients underwent GKRS for metastatic brain lesions originating from SCLC. Among these patients, 11 received prophylactic cranial irradiation (PCI) before the development of metastatic lesions (PCI group), and GKRS was performed as an initial treatment for newly diagnosed lesions in 12 patients who had not received PCI (primary GKRS group). In addition, GKRS was performed as a salvage treatment for progressive lesions after WBRT in 27 patients (salvage GKRS group). The medical records and imaging data of all patients were retrospectively analyzed. RESULTS: The overall survival of the 50 patients was 20.8 months (range 1-53) after the diagnosis of primary tumor and 12.0 months (range 1-47) after the development of cerebral metastasis. Median survival after GKRS was 4.8 months (range 1-15) in the PCI group, 4.6 months (range 0-18) in the primary GKRS group, and 7.6 months (range 0-33) in the salvage GKRS group. Further treatment for progressive lesions after GKRS was necessary in 15 patients, after a mean interval of 3.8 months. Causes of death were systemic organ failure in 15 patients, deterioration of neurological state in 13 patients, and unknown or combined causes in 16 patients. The local control rate of the lesions treated with GKRS was 76.4% (decreased in 13 patients and stable in 16 patients at the final imaging follow-up (mean 5.60 months). CONCLUSION: GKRS is an effective local treatment for brain metastasis from SCLC both as an initial treatment for newly diagnosed lesions after PCI and as a salvage treatment for recurrent or progressive lesions. However, the survival benefit is not significant because most patients die of systemic multi-organ failure with a short life expectancy. PMID- 22053228 TI - Chronic subdural hematoma treated by small or large craniotomy with membranectomy as the initial treatment. AB - OBJECTIVE: There are few studies comparing small and large craniotomies for the initial treatment of chronic subdural hematoma (CSDH) which had non-liquefied hematoma, multilayer intrahematomal loculations, or organization/calcification on computed tomography and magnetic resonance imaging. These procedures were compared to determine which would produce superior postoperative results. METHODS: Between 2001 and 2009, 317 consecutive patients were surgically treated for CSDH at our institution. Of these, 16 patients underwent a small craniotomy with partial membranectomy and 42 patients underwent a large craniotomy with extended membranectomy as the initial treatment. A retrospective review was performed to compare the postoperative outcomes of these two techniques, focusing on improvement of neurological status, complications, reoperation rate, and days of post-operative hospitalization. RESULTS: The mean ages were 69.4+/-12.1 and 55.6+/-9.3 years in the small and large craniotomy groups, respectively. The recurrence of hematomas requiring reoperation occurred in 50% and 10% of the small and large craniotomy patients, respectively (p<0.001). There were no significant differences in postoperative neurological status, complications, or days of hospital stay between these two groups. CONCLUSION: Among the cases of CSDH initially requiring craniotomy, the large craniotomy with extended membranectomy technique reduced the reoperation rate, compared to that of the small craniotomy with partial membranectomy technique. PMID- 22053229 TI - The effect of phosphodiesterase-4-specific inhibitor in the rat model of spinal nerve ligation. AB - OBJECTIVE: Peripheral neuropathy is characterized by hyperalgesia, spontaneous burning pain, and allodynia. The purpose of this study was to investigate the effect of rolipram, a phosphodiesterase-4-specific inhibitor, in a segmental spinal nerve ligation model in rats. METHODS: Both the L5 and L6 spinal nerves of the left side of the rats were ligated. Phosphodiesterase-4 inhibitor (rolipram) and saline (vehicle) were administered intraperitoneally. We measured mechanical allodynia using von Frey filaments and a nerve conduction study. RESULTS: The mechanical allodynia, which began to manifest on the first day, peaked within 2 days. Multiple intraperitoneal injections of rolipram ameliorated the mechanical allodynia. Furthermore, an intraperitoneal administration of rolipram improved the development of pain behavior and nerve conduction velocity. CONCLUSION: This study suggests that the phosphodiesterase-4 inhibitor, rolipram, alleviates mechanical allodynia induced by segmental spinal nerve ligation in rats. This finding may have clinical implications. PMID- 22053230 TI - Influence of history of brain disease or brain trauma on psychopathological abnormality in young male in Korea : analysis of multiphasic personal inventory test. AB - OBJECTIVE: The purpose of this study is to confirm whether brain disease or brain trauma actually affect psychopathology in young male group in Korea. METHODS: The authors manually reviewed the result of Korean military multiphasic personal inventory (KMPI) in the examination of conscription in Korea from January 2008 to May 2010. There were total 237 young males in this review. Normal volunteers group (n=150) was composed of those who do not have history of brain disease or brain trauma. Brain disease group (n=33) was consisted of those with history of brain disease. Brain trauma group (n=54) was consisted of those with history of brain trauma. The results of KMPI in each group were compared. RESULTS: Abnormal results of KMPI were found in both brain disease and trauma groups. In the brain disease group, higher tendencies of faking bad response, anxiety, depression, somatization, personality disorder, schizophrenic and paranoid psychopathy was observed and compared to the normal volunteers group. In the brain trauma group, higher tendencies of faking-good, depression, somatization and personality disorder was observed and compared to the normal volunteers group. CONCLUSION: Young male with history of brain disease or brain trauma may have higher tendencies to have abnormal results of multiphasic personal inventory test compared to young male without history of brain disease or brain trauma, suggesting that damaged brain may cause psychopathology in young male group in Korea. PMID- 22053231 TI - Glioblastoma mimicking herpes simplex encephalitis. AB - We report a case of 70-year-old man with glioblastoma presenting as acute encephalitic illness. The patient exhibited sudden onset of cognitive impairment and headache for 2 days. Initial brain MRI showed left temporal lobe hyperintensity, and cerebrospinal fluid cytology revealed a mild pleocytosis. The patient had initially improved after medical treatment with a presumptive diagnosis of herpes simplex encephalitis (HSE). After 8 months, the patient complained of recurrent seizures. A follow-up brain MRI revealed marked increases in size and surrounding perilesional edema in the left temporal lesion on T2 weighted images and a new contrast-enhancing lesion on gadolinium-enhanced T1 weighted images. Stereotactic brain biopsy revealed a glioblastoma. The atypical encephalitic presentation of glioblastoma should be considered if definitive evidence for the diagnosis of HSE cannot be obtained. PMID- 22053232 TI - Symptomatic tarlov cyst following spontaneous subarachnoid hemorrhage. AB - Most of Tarlov or perineurial cysts remain asymptomatic throughout the patient's life. The pathogenesis is still unclear. Hemorrhage has been suggested as one of the possible causes and trauma with resultant hemorrhage into subarachnoid space has been suggested as an origin of these cysts. However, Tarlov cysts related to spontaneous subarachnoid hemorrhage has not been reported. The authors report a case of Tarlov cyst which was symptomatic following spontaneous subarachnoid hemorrhage. PMID- 22053233 TI - Cerebral hemorrhage after endovascular treatment of bilateral traumatic carotid cavernous fistulae with covered stents. AB - Bilateral traumatic carotid-cavernous fistulae (TCCFs) is rarely encountered neurovascular disease. For treatment of TCCF, detachable balloons have been widely used. Nowadays, transarterial and/or transvenous coil embolization with placement of covered stents is adopted as another treatment method. We experienced a patient with a bilateral TCCFs who was successfully treated with covered stents. However, cerebral hemorrhage occurred in the bed of previous infarction one day after treatment. Hyperperfusion syndrome was considered as a possible cause of the hemorrhage, so that barbiturate coma therapy was started and progression of hemorrhage was stopped. We emphasize that cerebral hyperperfusion hemorrhage can occur even after successful endovascular treatment of TCCF. PMID- 22053234 TI - Idiopathic thoracic epidural lipomatosis with chest pain. AB - Spinal epidural lipomatosis (SEL) is an overgrowth of the normally encapsulated adipose tissue in the epidural space around the spinal cord in the thoracic and lumbar spine causing compression of the neural components. Idiopathic SEL in non obese patients is exceptional. Idiopathic SEL can result in thoracic myelopathy and lumbar radiculopathy. A thoracic radiculopathy due to idiopathic SEL has not been reported yet. We report a case of idiopathic SEL with intractable chest pain and paresthesia. We suggest that idiopathic SEL should be considered as a cause of chest pain. PMID- 22053235 TI - Dystrophic calcification in the epidural and extraforaminal space caused by repetitive triamcinolone acetonide injections. AB - The authors report a case of epidural and extraforaminal calcification caused by repetitive triamcinolone acetonide injections. A 66-year-old woman was admitted presenting with lower extremity weakness and radiating pain in her left leg. Ten months before admission, the patient was diagnosed as having an L4-5 spinal stenosis and underwent anterior lumbar interbody fusion followed by posterior fixation. Her symptoms had been sustained and she did not respond to transforaminal steroid injections. Repetitive injections (10 times) had been performed on the L4-5 level for six months. She had been taking bisphosphonate as an antiresorptive agent for ten months after surgery. Calcification in the ventral epidural and extraforaminal space was detected. The gritty particles were removed during decompressive surgery and these were proven to be a dystrophic calcification. The patient recovered from weakness and radiating leg pain. Repetitive triamcinolone acetonide injections after discectomy may be the cause of dystrophic calcification not only in the degenerated residual disc, but also in the posterior longitudinal ligament. Possible mechanisms may include the toxicity of preservatives and the insolubility of triamcinolone acetonide. We should consider that repetitive triamcinolone injections in the postdisectomy state may cause intraspinal ossification and calcification. PMID- 22053236 TI - Cervical fibrous dysplasia presenting as a pathologic fracture in an older patient. AB - Vertebral involvement of fibrous dysplasia (FD) is rare, especially in the cervical spine. Moreover, cervical FD presenting as a pathologic fracture in older patients is extremely rare. We report a case of symptomatic cervical FD associated with pathologic fracture in a 63-year-old man. The patient presented with progressive weakness of the left arm and pain in the shoulder and arm. Radiologic studies revealed a collapsed and typical 'ground glass' radiolucency of C4. Multiple lytic lesions involved the odontoid process of C2 and the body, left pedicle, and posterior elements of C4. Combined anterior and posterior decompression and reconstruction were performed. Post-operatively, the histopathologic examination confirmed FD. On the post-operative follow-up examination, the neurologic deficits had completely resolved. PMID- 22053237 TI - Intraparenchymal pericatheter cyst as a complication of a ventriculo-peritoneal shunt in a premature infant. AB - A ventriculo-peritoneal shunt is a standard surgical management for hydrocephalus, but complications may impede the management of this disease. Obstruction of the catheter is one of the most common complications and manifests clinically in various ways. Intraparenchymal cyst development after shunt malfunction has been reported by several authors, but the underlying mechanism and optimal treatment methods are debatable. The authors report a case of intraparenchymal cyst formation around a proximal catheter in a premature infant after a ventriculo-peritoneal shunt and discuss its pathogenesis and management. PMID- 22053238 TI - Cerebral actinomycosis : unusual clinical and radiological findings of an abscess. AB - We report a case of cerebral actinomycosis in a 69-year-old immunocompetent woman. The patient showed a progressive worsened mental status for one week. MRI examination showed an increased size of multiple enhancing nodular lesions associated with mild perilesional edema. We performed an open biopsy for the right frontal enhancing lesion. The intraoperative finding showed a yellowish friable lesion that was not demarcated with normal tissue. Pathologically, an actinomycotic lesion with sulfur granules and inflammatory cells was diagnosed. We report an unusual case of diffuse involvement of cerebral actinomycosis. The presence of the uncapsulated friable lesion that consisted mainly of foamy macrophages and lymphocytes could explain the unusual radiological features. PMID- 22053239 TI - Pulsed radiofrequency neuromodulation treatment on the lateral femoral cutaneous nerve for the treatment of meralgia paresthetica. AB - We describe a rare case of pulsed radiofrequency treatment for pain relief associated with meralgia paresthetica. A 58-year-old female presented with pain in the left anterior lateral thigh. An imaging study revealed no acute lesions compared with a previous imaging study, and diagnosis of meralgia paresthetica was made. She received temporary pain relief with lateral femoral cutaneous nerve blocks twice. We performed pulsed radiofrequency treatment, and the pain declined to 25% of the maximal pain intensity. At 4 months after the procedure, the pain intensity did not aggravate without medication. Pulsed radiofrequency neuromodulation treatment on the lateral femoral cutaneous nerve may offer an effective, low risk treatment in patients with meralgia paresthetica who are refractory to conservative medical treatment. PMID- 22053240 TI - Alternate metal framework designs for the metal ceramic prosthesis to enhance the esthetics. AB - PURPOSE: The objective of the present study was to evaluate the effect of five different metal framework designs on the fracture resistance of the metal-ceramic restorations. MATERIALS AND METHODS: For the purpose of this study, the central incisor tooth was prepared, and the metal analogue of it and a master die were fabricated. The counter die with the 0.5 mm clearance was used for fabricating the wax patterns for the metal copings. The metal copings with five different metal framework designs were designed from Group 1 to 5. Group 1 with the metal collar, Group 2, 3, 4 and 5 with 0 mm, 0.5 mm, 1 mm and 1.5 mm cervical metal reduction respectively were fabricated. Total of fifty metal ceramic crown samples were fabricated. The fracture resistance was evaluated with the Universal Testing Machine (Instron model No 1011, UK). The basic data was subjected to statistical analysis by ANOVA and Student's t-test. RESULTS: Results revealed that the fracture resistance ranged from 651.2 to 993.6 N/m(2). Group 1 showed the maximum and Group 5 showed the least value. CONCLUSION: The maximum load required to fracture the test specimens even in the groups without the metal collar was found to be exceeding the occlusal forces. Therefore, the metal frameworks with 0.5 mm and 1 mm short of the finish line are recommended for anterior metal ceramic restoration having adequate fracture resistance. PMID- 22053241 TI - Influence of cement thickness on resin-zirconia microtensile bond strength. AB - PURPOSE: The aim of this study was to evaluate the influence of resin cement thickness on the microtensile bond strength between zirconium-oxide ceramic and resin cement. MATERIALS AND METHODS: Thirty-two freshly extracted molars were transversely sectioned at the deep dentin level and bonded to air-abraded zirconium oxide ceramic disks. The specimens were divided into 8 groups based on the experimental conditions (cement type: Rely X UniCem or Panavia F 2.0, cement thickness: 40 or 160 um, storage: thermocycled or not). They were cut into microbeams and stored in 37C distilled water for 24 h. Microbeams of non thermocycled specimens were submitted to a microtensile test, whereas those of thermocycled groups were thermally cycled for 18,000 times immediately before the microtensile test. Three-way ANOVA and Sheffe's post hoc tests were used for statistical analysis (alpha=95%). RESULTS: All failures occurred at the resin zirconia interface. Thermocycled groups showed lower microtensile bond strength than non-thermocycled groups (P<.001). Differences in cement thickness did not influence the resin-zirconia microtensile bond strength given the same resin cement or storage conditions (P>.05). The number of adhesive failures increased after thermocycling in all experimental conditions. No cohesive failure was observed in any experimental group. CONCLUSION: When resin cements of adhesive monomers are applied over air-abraded zirconia restorations, the degree of fit does not influence the resin-zirconia microtensile bond strength. PMID- 22053242 TI - Curing efficiency of various resin-based materials polymerized through different ceramic thicknesses and curing time. AB - PURPOSE: The aim of this in vitro study was to examine the curing efficiency of various resin-based materials polymerized through ceramic restorations with 3 different thicknesses. Curing efficiency was evaluated by determining the surface microhardness (VHN) of the resin specimens. MATERIALS AND METHODS: Four kinds of resin materials were used. Z350 (3M ESPE FiltekTM Z350: A2 Shade), Z250 (3M ESPE FiltekTM Z250: A2 Shade) and Variolink(r) II (VL: Ivoclar vivadent, base: transparent) either with or without a self-curing catalyst (VLC: Ivoclar vivadent, catalyst: low viscosity/transparent) were filled into the silicone mold (10 mm diameter, 1 mm thick). They were cured through ceramic discs (IPS e.max Press MO-0 ingot ivoclar vivadent, 10 mm diameter, 0.5, 1 and 2 mm thicknesses) by LED light-curing units for 20 and 40 seconds. Vicker's microhardness numbers (VHNs) were measured on the bottom surfaces by a microhardness tester. Data were analyzed using a 3- way analysis of variance (ANOVA) at a significance level of 0.05. RESULTS: The thickness of ceramic disc increased, the VHNs of all four resin types were decreased (P<.05). The mean VHN values of the resins light cured for 40 seconds were significantly higher than that of LED for 20 seconds in all four resin materials (P<.05). VLC showed significantly higher VHN values than VL regardless of other conditions (P<.05). Z350 and Z250 showed higher values than VL or VLC (P<.01). CONCLUSION: Thinner ceramic disc with increased curing time resulted higher VHN values of all resin materials. The use of a catalyst produced a greater hardness with all polymerization methods. Restorative resin materials (Z350, Z250) showed higher VHN values than resin cement materials (VL, VLC). PMID- 22053243 TI - Occlusal scheme in a group of Thais. AB - PURPOSE: To study the distribution of various occlusal schemes as well as associated static occlusal relationship among Thais. MATERIALS AND METHODS: The subjects' occlusal schemes on the left and right sides were classified as canine protected occlusion, group function, or unclassified according to the definition from Glossary of Prosthodontic Terms (8(th) edition). In addition, the presence of occlusal interferences during mandibular excursions were recorded. The measurement of the horizontal overlap and vertical overlap was also performed. Chi-square, One-way ANAVA and Mann-Whitney U statistical tests were used with level of significance set at P=.05. RESULTS: Total of 104 subjects were included in this study. The ratio for male to female was 1.8 to 1. Average age of the population was 25.01+/-6.87 years old. The mean vertical overlap and horizontal overlap were 1.94+/-1.20 and 2.41+/-1.32 mm respectively. The majority of the populations (68.3%) possessed group function occlusal scheme. For the remaining, 17.3% possess canine protected occlusion and 12.5% possess combination of both occlusal schemes. We also found that occlusal interference was presented in 20.2% of the population. The most common was protrusive interference (57.14%), the second was balancing interference (38.1%) and the third was working interference (4.1%). CONCLUSION: Among Thais, the most common occlusal scheme was group function, however there were no significant occlusal factors related to any particular occlusal scheme. PMID- 22053244 TI - Flexural properties of a light-cure and a self-cure denture base materials compared to conventional alternatives. AB - PURPOSE: A new light curing urethane dimethacrylate and a cold curing resin with simpler and faster laboratory procedures may have even improved flexural properties. This study investigated the 3-point flexural strengths and flexural moduli of two alternate base materials. MATERIALS AND METHODS: A cold curing resin (Weropress) and a light curing urethane dimethacrylate base material (Eclipse). Along with Eclipse and Weropress, a high impact resin (Lucitone199) and three conventional base materials (QC 20, Meliodent and Paladent 20) were tested. A 3-point bending test was used to determine the flexural strengths and flexural moduli. The mean displacement, maximum load, flexural modulus and flexural strength values and standard deviations for each group were analyzed by means of one-way analysis of variance (ANOVA) (with mean difference significant at the 0.05 level). Post hoc analyses (Scheffe test) were carried out to determine the differences between the groups at a confidence level of 95%. RESULTS: Flexural strength, displacement and force maximum load values of Eclipse were significantly different from other base materials. Displacement values of QC 20 were significantly different from Lucitone 199 and Weropress. CONCLUSION: The flexural properties and simpler processing technique of Eclipse system presents an advantageous alternative to conventional base resins and Weropress offers another simple laboratory technique. PMID- 22053245 TI - Finite element study on the effect of abutment length and material on implant bone interface against dynamic loading. AB - PURPOSE: Finite element study on the effect of abutment length and material on implant bone interface against dynamic loading. MATERIALS AND METHODS: Two dimensional finite element models of cylinderical implant, abutments and bone made by titanium or polyoxymethylene were simulated with the aid of Marc/Mentat software. Each model represented bone, implant and titanium or polyoxymethylene abutment. Model 1: Implant with 3 mm titanium abutment, Model 2: Implant with 2 mm polyoxymethylene resilient material abutment, Model 3: Implant with 3 mm polyoxymethylene resilient material abutment and Model 4: Implant with 4 mm polyoxymethylene resilient material abutment. A vertical load of 11 N was applied with a frequency of 2 cycles/sec. The stress distribution pattern and displacement at the junction of cortical bone and implant was recorded. RESULTS: When Model 2, 3 and 4 are compared with Model 1, they showed narrowing of stress distribution pattern in the cortical bone as the height of the polyoxymethylene resilient material abutment increases. Model 2, 3 and 4 showed slightly less but similar displacement when compared to Model 1. CONCLUSION: Within the limitation of this study, we conclude that introduction of different height resilient material abutment with different heights i.e. 2 mm, 3 mm and 4 mm polyoxymethylene, does not bring about significant change in stress distribution pattern and displacement as compared to 3 mm Ti abutment. Clinically, with the application of resilient material abutment there is no significant change in stress distribution around implant-bone interface. PMID- 22053246 TI - The effect of immobilization of heparin and bone morphogenic protein-2 to bovine bone substitute on osteoblast-like cell's function. AB - PURPOSE: This study was performed to investigate the ability of recombinant human bone morphogenic protein-2 immobilized on a heparin-grafted bone substrate to enhance the osteoblastic functions. MATERIALS AND METHODS: The Bio-Oss(r), not coated with any material, was used as a control group. In rhBMP-2-Bio-Oss(r) group, rhBMP-2 was coated with Bio-Oss(r) using only deep and dry methods (50 ng/mL, 24 h). In heparinized rhBMP-2-Bio-Oss(r) group, dopamine was anchored to the surface of Bio-Oss(r), and coated with heparin. rhBMP-2 was immobilized onto the heparinized- Bio-Oss(r) surface. The release kinetics of the rhBMP-2-Bio Oss(r) and heparinized rhBMP-2-Bio-Oss(r) were analyzed using an enzyme-linked immunosorbent assay. The biological activities of the MG63 cells on the three groups were investigated via cytotoxicity assay, cell proliferation assay, alkaline phosphatase (ALP) measurement, and calcium deposition determination. Statistical comparisons were carried out by one-way ANOVA test. Differences were considered statistically significant at (*)P<.05 and (**)P<.001. RESULTS: The heparinized rhBMP-2-Bio-Oss(r) showed more sustained release compared to the rhBMP-2-Bio-Oss(r) over an extended time. In the measurement of the ALP activity, the heparinized group showed a significantly higher ALP activity when compared with the non-heparinized groups (P<.05). The MG63 cells cultivated in the group with rhBMP-2 showed increased calcium deposition, and the MG63 cells from the heparinized group increased more than those that were cultivated in the non heparinized groups. CONCLUSION: Heparin increased the rhBMP-2 release amount and made sustained release possible, and heparinized Bio-Oss(r) with rhBMP-2 successfully improved the osteoblastic functions. PMID- 22053247 TI - Effects of the immobilization of heparin and rhPDGF-BB to titanium surfaces for the enhancement of osteoblastic functions and anti-inflammation. AB - PURPOSE: This study was to investigate the effects of recombinant human platelet derived growth factor (rhPDGF-BB) and heparin to titanium surfaces for enhancement of osteoblastic functions and inhibition of inflammation activity. MATERIALS AND METHODS: The anodized titanium discs, not coated with any material, were used as a control group. In heparinized- Ti group, dopamine was anchored to the surface of Ti substrates, and coated with heparin. In PDGF-Ti group, rhPDGF BB was immobilized onto heparinized Ti surface. The surface morphologies were investigated by the scanning electron microscope in each group. The release kinetics of rhPDGF-BB were analyzed, and cytotoxicity tests for each group were conducted. The biocompatibilities were characterized by measuring cell proliferation, alkaline phosphatase activity, and calcium deposition using MG-63 cells. Statistical comparisons were carried out by one-way ANOVA tests. Differences were considered statistically significant at (*)P<.05 and (**)P<.001. RESULTS: The combination of rhPDGF-BB and heparin stimulated alkaline phosphatase activity and OCN mRNA expression in osteoblastic cells ((*)P<.05 and (**)P<.001). MG-63 cells grown on PDGF-Ti had significantly higher amounts of calcium deposition than those grown on anodized Ti ((**)P<.001). Heparinized Ti was more anti-inflammatory compared to anodized Ti, when exposed to lipopolysaccharide using the transcript levels of TNF-alpha and IL-6 of proinflammatory cytokine ((*)P<.05 and (**)P<.001). CONCLUSION: The result of this study demonstrated that the incorporation of rhPDGF-BB and heparin onto Ti surface enhanced osteoblastic functions and inhibited inflammation. PMID- 22053248 TI - Randomized clinical trial on the efficacy of Escherichia coli-derived rhBMP-2 with beta-TCP/HA in extraction socket. AB - PURPOSE: This randomized clinical trial was conducted to assess the safety and effectiveness of the ErhBMP-2 in alveolar bone regeneration as well as preservation of the beta-TCP bone graft material that contains ErhBMP-2. MATERIALS AND METHODS: This study involved 72 patients at the 3 study centers. The patients, who were divided into 2 groups: the experiment group who had ErhBMP 2 coated TCP/HA and the control group who had TCP/HA graft material alone transplanted immediately after tooth extraction. CT was taken before and 3 months after the transplantation and healing status was compared between the two groups. The efficacy endpoints that were used to measure the degree of bone induction included alveolar bone height and 3 measurements of bone width. The paired t test was used to determine the significance of the changes (P<.05). RESULTS: Changes in alveolar bone height were -1.087 +/- 1.413 mm in the control group and -.059 +/- 0.960 mm in the experimental group (P<.01). At 25% extraction socket length [ESL], the changes were 0.006 +/- 1.149 mm in the control group and 1.279 +/- 1.387 mm in the experimental group. At 50% ESL, the changes were 0.542 +/- 1.157 mm and 1.239 +/- 1.249 mm, respectively (P<.01 for 25% ESL, and P<.05 for 50% ESL). During the experiment, no adverse reactions to the graft material were observed. CONCLUSION: ErhBMP-2 coated beta-TCP/HA were found to be more effective in preserving alveolar bone than conventional beta-TCP/HA alloplastic bone graft materials. PMID- 22053249 TI - Evaluation of shear bond strengths of gingiva-colored composite resin to porcelain, metal and zirconia substrates. AB - PURPOSE: The purpose of this study is to evaluate and compare the shear bond strength of the gingiva-colored composite resin and the tooth-colored composite resin to porcelain, metal and zirconia. MATERIALS AND METHODS: Sixty cylindrical specimens were fabricated and divided into the following 6 groups (Group 1-W: tooth-colored composite bonded to porcelain, Group 1-P: gingiva-colored composite bonded to porcelain, Group 2-W: tooth-colored composite bonded to base metal, Group 2-P: gingiva-colored composite bonded to base metal, Group 3-W: toothcolored composite bonded to zirconia, Group 3-P: gingiva-colored composite bonded to zirconia). The shear bond strength was measured with a universal testing machine after thermocycling and the failure mode was noted. All data were analyzed using the two-way analysis of variance test and the Bonferroni post-hoc test at a significance level of 0.05. RESULTS: The mean shear bond strength values in MPa were 12.39, 13.42, 8.78, 7.98, 4.64 and 3.74 for Group 1-W, 1-P, 2 W, 2-P, 3-W and 3-P, respectively. The difference between the two kinds of composite resin was not significant. The shear bond strength of Group 1 was the highest and that of Group 3 was the lowest. The differences among Group 1, 2 and 3 were all significant (P<.05). CONCLUSION: The shear bond strength of the gingiva-colored composite was not less than that of the tooth-colored composite. Thus, repairing or fabricating ceramic restorations using the gingiva-colored composite resin can be regarded as a practical method. Especially, the prognosis would be fine when applied on porcelain surfaces. PMID- 22053250 TI - Guide flange prosthesis for early management of reconstructed hemimandibulectomy: a case report. AB - Surgical resection of the mandible due to presence of benign or malignant tumor is the most common cause of the mandibular deviation. Depending upon the location and extent of the tumor in the mandible, various surgical treatment modalities like marginal, segmental, hemi, subtotal, or total mandibulectomy can be performed. The clinicians must wait for extensive period of time for completion of healing and acceptance of the osseous graft before considering the definitive prosthesis. During this initial healing period prosthodontic intervention is required for preventing the mandibular deviation. This case report describes early prosthodontic management of a patient who has undergone a reconstructed hemi-mandibulectomy with modified mandibular guide flange prosthesis. The prosthesis helps patient moving the mandible normally without deviation during functions like speech and mastication. PMID- 22053251 TI - Injury pattern due to falls from hunting stands. AB - Hunting is a historically constructed cultural act and continues to be a passion and a popular recreational pastime worldwide. Along with a high population density in Europe and a large volume of hunters hunting injuries such as falls from hunting stands continue to occur regularly and are a significant cause of morbidity among hunters. The purpose of this study was to review typical injury patterns after falls from hunting stands in Germany between 2000-2009 using the German agricultural statutory accident insurance database and to compare these findings to other causes of hunting accidents. The most common injury pattern after falls from hunting stands in Germany in the period of 2000-2009 are closed fractures. However, data collection is incomplete. Thus a more precise data collection would help to be able to better analyze accident mechanisms in order to be able to prevent further accidents. PMID- 22053252 TI - Delayed gadolinium-enhanced magnetic resonance imaging of hip joint cartilage: pearls and pitfalls. AB - With the increasing advances in hip joint preservation surgery, accurate diagnosis and assessment of femoral head and acetabular cartilage status is becoming increasingly important. Magnetic resonance imaging (MRI) of the hip does present technical difficulties. The fairly thin cartilage lining necessitates high image resolution and high contrast-to-noise ratio (CNR). With MR arthrography (MRA) using intraarticular injected gadolinium, labral tears and cartilage clefts may be better identified through the contrast medium filling into the clefts. However, the ability of MRA to detect varying grades of cartilage damage is fairly limited and early histological and biochemical changes in the beginning of osteoarthritis (OA) cannot be accurately delineated. Traditional MRI thus lacks the ability to analyze the biological status of cartilage degeneration. The technique of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) is sensitive to the charge density of cartilage contributed by glycosaminoglycans (GAGs), which are lost early in the process of OA. Therefore, the dGEMRIC technique has a potential to detect early cartilage damage that is obviously critical for decision-making regarding time and extent of intervention for joint-preservation. In the last decade, cartilage imaging with dGEMRIC has been established as an accurate and reliable tool for assessment of cartilage status in the knee and hip joint.This review outlines the current status of dGEMRIC for assessment of hip joint cartilage. Practical modifications of the standard technique including three-dimensional (3D) dGEMRIC and dGEMRIC after intra-articular gadolinium instead of iv-dGEMRIC will also be addressed. PMID- 22053253 TI - Postoperative blood loss reduction in computer-assisted surgery total knee replacement by low dose intra-articular tranexamic acid injection together with 2 hour clamp drain: a prospective triple-blinded randomized controlled trial. AB - A high-dose local tranexamic acid has been introduced in total knee arthroplasty for bleeding control. We are not sure about the systemic absorption and side effects. The aim of this study was to evaluate the effect of low dosage of intra articular tranexamic acid injection combined with 2-hour clamp drain in minimally bleeding computer-assisted surgery total knee replacement (CAS-TKR). A prospective randomized controlled trial was conducted in a total of 48 patients underwent CAS-TKR. The patients were randomly assigned to receive either of a mixed intra-articular solution of tranexamic acid 250 mg with physiologic saline (TXA group), or physiologic saline (control group) and then followed by clamp drain for 2 hours. Postoperative blood loss was measured by three different methods as drainage volume, total hemoglobin loss and calculated total blood loss. Transfusion requirement and postoperative complications were recorded. All patients were screened for deep vein thrombosis and the functional outcomes were evaluated at 6 months after surgery. The mean postoperative drainage volume, total hemoglobin loss and calculated total blood loss in TXA group were 308.8 mL, 2.1 g/dL and 206.3 mL compared to 529.0 mL, 3.0 g/dL and 385.1 mL in the control group (P=0.0003, 0.0005 and <0.0001 respectively). Allogenic blood transfusion was needed for one patient (4.2%) in TXA group and for eight patients (33.3%) in the control group. Postoperative knee scores were not significantly different between groups. No deep vein thrombosis, infection or wound complication was detected in both groups. In this study, low dose intra-articular tranexamic acid injection combined with 2-hour clamping drain was effective for reducing postoperative blood loss and transfusion requirement in CAS-TKR without significant difference in postoperative complications or functional outcomes. PMID- 22053254 TI - Hip arthrodesis in the pediatric population: where do we stand? AB - Reconstructive and salvage procedures have continued to evolve in orthopedic surgery with changing functional demands of the population as well as advances in implants and surgical techniques. What used to be popular or traditional care at some point may eventually become a thing of the past, and this is true as far as many orthopedic surgical procedures are concerned. Understanding the etiology, pathogenesis, and managing and postponing the destructive pathway of osteoarthritis (OA) has been the goal of orthopedists since the specialty began in the early part of 18(th) century. Options of treating the severe sequelae of an arthritic joint have varied in different treatment eras. Management options have changed from a spectrum of non-treatment and slow suffering to muscle and soft-tissue releases, interposition arthroplasty and eventual extreme options like joint fusion or arthrodesis. The concept and advent of joint replacement surgery started a new era in the management of OA and was a dream come true in many ways. Mobility and stability are achieved together during the arthroplasty (joint replacement) that allowes the patient to maintain a good level of function. Arthroplasty certainly has its pros and cons as we have discovered in the past six decades. Pushing the envelope to younger population has its limitation in terms of longevity of the prosthesis, early loosening, need for repeated revisions that at some point may not be technically possible and risk of infection and disastrous consequences like PE and death associated with the gravity of the procedure. As infrequent as it is in today's clinical practice, arthrodesis of the hip joint has a role and remains a solid option for a well selected case.The purpose of this review is to discuss the current indications in the pediatric population and outline surgical techniques for hip arthrodesis while pointing out limitations and shortcomings. PMID- 22053255 TI - Misdiagnosis of early Lyme disease as the summer flu. AB - Lyme disease is often identified by the hallmark erythema migrans rash, but not all early cases present with a rash. In other cases the rash may be unseen or unrecognized by a physician. In these situations, Lyme disease is difficult to diagnose because it masquerades as a non-specific viral-like illness. The seasonal peak of Lyme disease ranging from May through September overlaps with that of viral illnesses such as enteroviral infections, West Nile virus, and in rare years such as 2009, early influenza season. We present a case of a patient with Lyme disease who was initially misdiagnosed with influenza A during the summer of 2009. Because of the diagnostic importance of recognizing the erythema migrans rash, physicians in endemic regions should always ask about new rashes or skin lesions and perform a thorough physical examination when patients present over the summer with viral-like symptoms. Even when no rash is evident, Lyme disease should be considered if these symptoms persist or worsen without a specific diagnosis. PMID- 22053256 TI - Magnetic resonance imaging of hip joint cartilage and labrum. AB - Hip joint instability and impingement are the most common biomechanical risk factors that put the hip joint at risk to develop premature osteoarthritis. Several surgical procedures like periacetabular osteotomy for hip dysplasia or hip arthroscopy or safe surgical hip dislocation for femoroacetabular impingement aim at restoring the hip anatomy. However, the success of joint preserving surgical procedures is limited by the amount of pre-existing cartilage damage. Biochemically sensitive MRI techniques like delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) might help to monitor the effect of surgical or non-surgical procedures in the effort to halt or even reverse joint damage. PMID- 22053258 TI - Benign fasciculations and corticosteroid use: possible association? An update. AB - Fasciculations are characterized by visible subtle and fast contractions of muscle, even wormlike in movement, by the contraction of a fascicle of muscle fibers. The authors present the case study of a 28-year-old patient with the appearance of migratory and diffuse fasciculations with an onset after partial tapering off of oral corticosteroides (60 mg total dose) indicated for treatment of Minimal change Glomerulopathy. Clinical Neurological physical exam allied with an ENMG, besides other complementary laboratory exams were used for screening the above-mentioned patient. Afterwards, current research relating to the topic at hand was made in order to update the data available in the Bireme, Scielo and PubMed Data Banks using the following key words: Fasciculation's, motor neuron disease, and benign fasciculations in the Portuguese, English as well as Spanish language. Although fasciculation's are most commonly associated with Motor neuron disease as well as with certain metabolic disorders, they may also be present in individuals with absolutely no underlying pathological disorders. In our case, fasciculation potentials that have been present for six months, with no other signs of a neurogenic disorder as well as absence of laboratory findings, the patient received a diagnosis of Benign Fasciculation Syndrome (BFS).We believe that the use of corticosteroides in high doses with subsequent tapering contributed to the fasciculation's, especially due to the changes that this causes on the ionic channels. Fasciculation's are symptoms seen in a large range of conditions, and also being the main symptom of the so-called Benign Fasciculation Syndrome. We have presented an example of this clinical syndrome in a patient whose complaint was fasciculation's, with complete clinical remission of symptoms following complete tapering off of corticosteroid six months previously. PMID- 22053257 TI - Behavioral outcome measures used for human neural stem cell transplantation in rat stroke models. AB - Stroke is a leading cause of death and disability, leading to the development of various stroke models to test new treatments, most commonly in the rat. Human stroke trials focus on disability, related primarily to neurological deficits. To better model the clinical application of these treatments, many behavioral tests have been developed using the rat stroke model. We performed a systematic review of all the behavioral outcome measures used in published studies of human neural stem cell transplantation in rat stroke models. The reviewed tests include motor, sensory, cognitive, activity, and combination tests. For each test, we give a brief description, trace the origin of the test, and discuss test performance in the reviewed studies. We conclude that while many behavioral tests are available for this purpose, there does not appear to be consensus on an optimal testing strategy. PMID- 22053259 TI - Primary stroke prevention and hypertension treatment: which is the first-line strategy? AB - Hypertension (HT) is considered the main classic vascular risk factor for stroke and the importance of lowering blood pressure (BP) is well established. However, not all the benefit of antihypertensive treatment is due to BP reduction per se, as the effect of reducing the risk of stroke differs among classes of antihypertensive agents. Extensive evidences support that angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), dihydropyridine calcium channel blockers (CCB) and thiazide diuretics each reduced risk of stroke compared with placebo or no treatment. Therefore, when combination therapy is required, a combination of these antihypertensive classes represents a logical approach. Despite the efficacy of antihypertensive therapy a large proportion of the population, still has undiagnosed or inadequately treated HT, and remain at high risk of stroke. In primary stroke prevention current guidelines recommend a systolic/diastolic BP goal of <140/<90 mmHg in the general population and <130/80 mmHg in diabetics and in subjects with high cardiovascular risk and renal disease. The recent release in the market of the fixed-dose combination (FDC) of ACEI or ARB and CCB should provide a better control of BP. However to confirm the efficacy of the FDC in primary stroke prevention, clinical intervention trials are needed. PMID- 22053260 TI - Novel mutation of the notch3 gene in arabic family with CADASIL. AB - Mutations in the NOTCH3 gene are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), an adult onset hereditary angiopathy leading to ischemic stroke, vascular dementia and psychiatric disorders. All mutation of NOTCH3 described so far are striking stereotyped leading to the gain or loss of cystiene residue in a given epidermal growth factor (EGF), like repeat. We report an Arabic family affected with CADASIL mutation, G1790 C, in Exon 11 of the NOTCH3 gene. This is the first novel mutation reported in Arabic CADASIL patients. This finding confirms that mutations in NOTCH3 are associated with the pathogenesis of CADASIL across different ethnic background. PMID- 22053261 TI - Parkinson's disease: an inquiry into the etiology and treatment. AB - Parkinson's disease affects over one million people in the United States. Although there have been remarkable advances in uncovering the pathogenesis of this disabling disorder, the etiology is speculative. Medical treatment and operative procedures provide symptomatic relief only. Compression of the cerebral peduncle of the midbrain by the posterior cerebral artery in a patient with Parkinson's Disease (Parkinson's Disease) was noted on magnetic resonance imaging (MRI) scan and at operation in a patient with trigeminal neuralgia. Following the vascular decompression of the trigeminal nerve, the midbrain was decompressed by mobilizing and repositioning the posterior cerebral artery The patient's Parkinson's signs disappeared over a 48-hour period. They returned 18 months later with contralateral peduncle compression. A blinded evaluation of MRI scans of Parkinson's patients and controls was performed. MRI scans in 20 Parkinson's patients and 20 age and sex matched controls were evaluated in blinded fashion looking for the presence and degree of arterial compression of the cerebral peduncle. The MRI study showed that 73.7 percent of Parkinson's Disease patients had visible arterial compression of the cerebral peduncle. This was seen in only 10 percent of control patients (two patients, one of whom subsequently developed Parkinson's Disease); thus 5 percent. Vascular compression of the cerebral peduncle by the posterior cerebral artery may be associated with Parkinson's Disease in some patients. Microva-scular decompression of that artery away from the peduncle may be considered for treatment of Parkinson's Disease in some patients. PMID- 22053262 TI - Cervical spine intradural-extramedullary hematoma presenting as ipsilateral hemiparesis. AB - A 75-year-old Taiwanese man suffered from acute onset of right-sided extremity weakness while talking to his neighbors. He was transferred to the hospital within three-hour time after symptom onset. Initial acute ischemic cerebral infarct was diagnosed based on his symptom and cerebral computed tomography. Thrombolytic therapy was held after his symptom improved promptly and could not excluded other etiology. Thorough history taking unraveled previous Chinese medicine clinic visit because of neck sore. However, he received limited improvement after several times of massage treatment. Magnetic resnance imaging (MRI) of the cervical spine demonstrated hematoma compressing right side intradural-extramedullary space at the C2/C3 level. Through his clinical course, muscle weakness was the sole neurological finding with sparing of sensory defects. Given the close anatomy relationship between sensory and motor lamina distribution in the cervical spinal cord, our patient presented a rare manifestation. Cases of cervical spine intradural-extramedullary hematoma are not often seen and only sporadic in the documented literature. We wish, through the report of this article, to inform the first- line physicians with the following information. Among the elderly, neck sore is a common symptom. Over- stretching or overt local massage is not suggested due to relatively fragile musculature. In the clinical diagnosis and localization of lesion, cerebral or cervical spine lesion could mimic with each other and manifest hemiparesis as their first symptom. Meticulous history taking, neurological/ physical examination and pertinent laboratory work-up should be done before initiation of intravenous thrombolytic therapy as it could cause catastrophic consequences if not used properly. PMID- 22053263 TI - Neuroleptic malignant syndrome due to risperidone misdiagnosed as status epilepticus. AB - Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal disease characterized by fever, muscle rigidity, delirium and autonomic instability. Here we report a child, with NMS due to the risperidone misdiagnosed as status epilepticus. Nine year old boy, who had been under high dose risperidone treatment for 8 weeks, admitted to the emergency room because of the contractions (evaluated as status epilepticus) persisting for 7 hours. Since there was neuroleptic treatment in the past medical history and, unconsciousness, muscular rigidity, diaphoresis, hypertermi and, hypotension in physical examination, leucocytosis and elevated creatininphosphokinase levels in laboratory tests, the patient was evaluated as NMS and discharged without any complications. We reported this case to point out that; NMS may be misdiagnosed as status epilepticus in children when EEG monitoring is unavailable. When a child admitted to the emergency room because of suspicious convulsion neuroleptic drug use must surely be asked. PMID- 22053264 TI - Three Japanese patients with congenital pituitary hormone deficiency and ophthalmological anomalies. AB - The clinical phenotype of congenital pituitary hormone deficiency is variable and can be associated with a number of structural abnormalities of the central nervous system. We report three Japanese patients with congenital pituitary hormone deficiency and ophthalmological anomalies. Two of the patients initially showed strabismus and unilateral optic nerve hypoplasia. Thereafter, growth failure became evident, leading to the diagnosis of pituitary hormone deficiency. The other patient had severe congenital hypopituitarism with respiratory distress and hypoglycemia from the first day of life. In addition, he had prolonged jaundice and impaired liver function with bilateral optic nerve hypoplasia. Neuroimaging of the pituitary region in all three patients demonstrated a small anterior pituitary lobe and no pituitary stalk. Our findings indicate that clinical variability of congenital hypopituitarism must be considered. In a patient with ophthalmological symptoms, endocrine evaluation and neuroimaging of the CNS including the pituitary region should be considered. PMID- 22053265 TI - Cystic fibrosis-related liver disease: a single-center experience. AB - Prospective studies concerning liver disease in pediatric cystic fibrosis patients are scarce. The present study aimed to describe the prevalence and clinical expression of cystic fibrosis - related liver disease, in a cohort of 62 pediatric patients. Descriptive study, resulting from the prospective evaluation, between 1994 and 2009, of 62 pediatric patients (age <18 years) with cystic fibrosis. The follow-up protocol included a clinical assessment every 2 months, liver function tests every 6 months and annual liver ultrasonography. The cumulative prevalence of liver disease was 11.2% (7/62 cases). All patients had DeltaF508 mutation and pancreatic insufficiency, none had meconium ileus. The liver involvement became clinically evident at a mean age of 8 years (3-15 years), revealed by hepatomegaly or hepatosplenomegaly (3 cases) and/ or abnormalities of liver function tests (3 cases) changes of liver ultrasound (7 cases) with evidence of portal hypertension (2 cases). Four patients were submitted to liver biopsy; biliary fibrosis was documented in one case, focal biliary cirrhosis in 2 cases and multilobular cirrhosis in another case. Within a median 11.6 years follow-up period (all patients under UDCA therapy after liver disease diagnosis), progression of liver disease was observed in 2 patients; one patient developed refractory variceal bleeding and progressive hepatic failure, requiring liver transplant. The results of the present study agree with those of previous pediatric studies, further documenting clinical expression of liver disease in CF patients, which is usually detected in the first decade of life and emphasize the contribution of ultrasound to early diagnosis of liver involvement. Moreover, although advanced liver disease is a relatively rare event, early isolated liver transplantation may have to be considered at this age group. PMID- 22053266 TI - Omental infarction in an obese 10-year-old boy. AB - Primary omental infarction (POI) has a low incidence worldwide, with most cases occurring in adults. This condition is rarely considered in the differential diagnosis of acute abdominal pain in childhood. Herein, we present a case of omental infarction in an obese 10-year-old boy who presented with acute abdominal pain in the right lower abdomen. The ultrasound (US) examination did not reveal the appendix but showed secondary signs suggesting acute appendicitis. The child was thus operated on under the preoperative diagnosis of acute appendicitis but the intra-operative finding was omental infarct. Since the omental infarct as etiology of acute abdominal pain is uncommon, we highlight some of the possible etiologies and emphasize the importance of accurate diagnosis and appropriate treatment of omental infarction. PMID- 22053267 TI - Current approaches to pediatric heart catheterizations. AB - Sedation for pediatric cardiac catheterization is a common requirement in many institutions. As the field of cardiac catheterization has evolved, the provision of sedation for these procedures has been varied. Increasingly the demand is for dedicated personnel focused on monitoring and delivery of sedation while in the catheterization suite. This article describes the considerations one must use when undertaking these cases. PMID- 22053268 TI - Temporary brittle bone disease: relationship between clinical findings and judicial outcome. AB - There is a wide differential diagnosis for the child with unexplained fractures including non-accidental injury, osteogenesis imperfecta and vitamin D deficiency rickets. Over the last 20 years we and others have described a self-limiting syndrome characterised by fractures in the first year of life. This has been given the provisional name temporary brittle bone disease. This work had proved controversial mostly because the fractures, including rib fractures and metaphyseal fractures, were those previously regarded as typical or even diagnostic of non-accidental injury. Some have asserted that the condition does not exist. Over the years 1985 to 2000 we investigated 87 such cases with fractures with a view to determining the future care of the children. In 85 of these the judiciary was involved. We examined the clinical and radiological findings in the 33 cases in which there was a judicial finding of abuse, the 24 cases in which the parents were exonerated and the 28 cases in which no formal judicial finding was made. The three groups of patients were similar in terms of demographics, age at fracturing and details of the fractures. The clinical similarities between the three groups of patients contrast with the very different results of the judicial process. PMID- 22053269 TI - An incidental finding in a preoperative chest radiograph. PMID- 22053270 TI - Death rates from lung cancer surgery have almost halved over 10 years. PMID- 22053271 TI - Acute lymphoblastic leukemia in adults. AB - Acute lymphoblastic leukemia (ALL) is the most frequent neoplastic disease in children, being a rare disease in adults. Many of the advances in pediatric ALL have been through modifications in the doses and schedules of available agents as opposed to the introduction of new compounds. In recent years some improvements in the outcome of ALL in adults have occurred. Application of pediatric regimens to young and middle-aged adults shows promise to improve outcome. Advances in the supportive care of patients undergoing allogeneic stem cell transplantation (SCT), the use of alternative sources of hematopoietic stem cells and the use of reduced-intensity conditioning regimens will expand the number of patients who can benefit from this therapeutic modality. The evaluation of minimal residual disease will further stratify risk classification and redefine the role of therapeutic modalities such as SCT or biologic agents. New drugs such as thyrosin kinase inhibitors or monoclonal antibodies have led to incremental improvements in outcome. Advances in the genetic and epigenetic mechanisms of the disease provide hope that targeted therapies can more effectively treat the disease with less toxicity. PMID- 22053272 TI - The role of haploinsufficiency of RPS14 and p53 activation in the molecular pathogenesis of the 5q- syndrome. AB - In recent years we have gained great insight into the molecular pathogenesis of the 5q- syndrome, a distinct subtype of myelodysplasia. The demonstration of haploinsufficiency of the ribosomal gene RPS14 (mapping to the commonly deleted region) and the finding that this is the cause of the erythroid defect in the 5qsyndrome represent major advances. A mouse model of the human 5q- syndrome generated by large-scale deletion of the Cd74-Nid67 interval (containing RPS14) further supports a critical role for RPS14 haploinsufficiency. It is widely accepted that ribosomal deficiency results in p53 activation and defective erythropoiesis and the crossing of the '5q- mice' with p53 deficient mice ameliorated the erythroid progenitor defect. Emerging data suggests that the p53 activation observed in the mouse model may also apply to the human 5q- syndrome. PMID- 22053273 TI - Reduced intensity transplantation for primary immunodeficiency disorders. AB - Studies so far indicate that reduced intensity transplantation (RIT) may have an important role in treating patients with primary immunodeficiency disease (PID). Unlike more standard approaches, such regimens can be used without severe toxicity in patients with severe pulmonary or hepatic disease. RIT also offers the advantage that long-term sequelae such as infertility or growth retardation may be avoided or reduced. RIT appears to be most appropriate for those patients with significant co-morbidities (eg T cell deficiencies) and those undergoing unrelated donor haematopoietic cell transplantation. More studies are required using pharmacokinetic monitoring (eg busulphan, treosulfan and alemtuzumab) and varying stem cell sources to optimise graft vs marrow reactions and minimise graft vs host disease. In certain PID patients RIT will be the "first step" towards establishing donor cell engraftment; second infusions of donor stem cells, donor lymphocyte infusions, or a second myeloablative HCT, which appears to be well tolerated, may be required in some patients with low level donor chimerism or graft rejection. PMID- 22053274 TI - HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors. AB - Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing's sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT) allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an event-free survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemotherapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results. PMID- 22053275 TI - T cell-depleted hla-haploidentical stem cell transplantation in thalassemia young patients. PMID- 22053276 TI - T cell depleted haploidentical transplantation: positive selection. AB - Interest in mismatched transplantation arises from the fact that a suitable one haplotype mismatched donor is immediately available for virtually all patients, particularly for those who urgently need an allogenic transplant. Work on one haplotype-mismatched transplants has been proceeding for over 20 years all over the world and novel transplant techniques have been developed. Some centres have focused on the conditioning regimens and post transplant immune suppression; others have concentrated on manipulating the graft which may be a megadose of extensively T celldepleted or unmanipulated progenitor cells. Excellent engraftment rates are associated with a very low incidence of acute and chronic GVHD and regimen-related mortality even in patients who are over 50 years old. Overall, event-free survival and transplant-related mortality compare favourably with reports on transplants from sources of stem cells other than the matched sibling. PMID- 22053277 TI - Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide. AB - Allogeneic stem cell transplantation (SCT) from an HLA-haploidentical relative provides a potentially curative treatment option for hematologic malignancies patients who lack a suitably HLA-matched donor. The greatest challenge to performing HLA-haploidentical SCT has been high rates of graft failure and severe graft-versus-host disease (GVHD). Our group has been exploring high dose, post transplantation cyclophosphamide (Cy) as prophylaxis of GVHD after nonmyeloablative, HLA-haploidentical bone marrow transplantation, or mini haploBMT. Among 210 recipients of mini-haploBMT, 87% of patients have experienced sustained donor cell engraftment. The cumulative incidences of grades II-IV acute GVHD and chronic GVHD are 27% and 13%, respectively. Five-year cumulative incidence of non-relapse mortality is 18%, relapse is 55%, and actuarial overall survival and event-free survivals are 35% and 27%, respectively. These outcomes suggest that mini-haploBMT with post-transplantation Cy is associated with acceptably low toxicities and can provide longterm survival, if not cure, for many patients with advanced hematologic malignancies. PMID- 22053278 TI - Acute lymphoblastic leukemia: age and biology. AB - Acute lymphoblastic leukemia (ALL) is the most frequent neoplasm in children, while being relatively rare in adults. The outcome of children with ALL is far superior than that observed in adults, whose survival rates generally do not exceed 40%. A retrospective analysis recently carried out on a large series of cases enrolled in the AIEOP and GIMEMA protocols for the treatment of pediatric and adult ALL has documented specific differences among the various age cohorts examined, particularly in terms of incidence of molecular rearrangements, with the BCR/ABL rearrangement being detected in more than half of patients in the 6(th) decade of life. These findings highlight the importance of a precise diagnostic screening at all ages, since elderly patients might benefit more from targeted approaches, that are associated with less toxic effects. Furthermore, extended biologic approaches aimed at identifying novel therapeutic targets should be regarded as a main goal to refine our therapeutic armamentarium.Finally, the introduction of pediatric-like protocols is progressively changing the outcome of young adult patients, although an important caveat is represented by the comorbidities and toxic effects associated with more aggressive chemotherapy; therefore, patients' fitness should always be carefully considered. PMID- 22053279 TI - Myeloid/T-cell acute lymphoblastic leukemia in children and adults. AB - Until recently, few molecular aberrations were recognized in T-cell acute lymphoblastic leukemia (T-ALL) and they were restricted to aberrations involving the T-cell receptor (TCR). The introduction of powerful technologies has allowed to identify novel rearrangements. In this context, we have performed a gene expression profiling analysis on a relatively large cohort (n=69) of adult patients with a diagnosis of T-ALL. By unsupervised clustering, we identified 5 subgroups. Of these, one branch included 7 patients (10%) whose gene expression profile resembled that of AML. These cases were characterized by the overexpression of a large set of myeloid-related genes, as well as of miR-223. Finally, these patients appear to have an unfavorable clinical course. This newly identified subset of T-ALL cases partly resembles the so-called ETP (early T precursor) pediatric subgroup: both age groups have in fact a peculiar gene expression profile, an unfavorable outcome and an incidence of about 10%. PMID- 22053280 TI - New genetics and diagnosis of childhood B-cell precursor acute lymphoblastic leukemia. AB - Over the last 50 years, while significant advances have been made in the successful treatment of childhood leukaemia, similar progress has been made in understanding the genetics of the disease. In childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), the incidences of individual chromosomal abnormalities are well established and cytogenetics provides a reliable tool for risk stratification for treatment. In spite of this role, a number of patients will relapse. Increasing numbers of additional genetic changes, including deletions and mutations, are being discovered. Their associations with established cytogenetic subgroups and with each other remain unclear. Whether they have a link to outcome is the most important factor in terms of refinement of risk factors in relation to clinical trials. For a number of newly identified abnormalities, appropriately modified therapy has significantly improved outcome. Alternatively, some of these aberrations are providing novel molecular markers for targeted therapy. PMID- 22053281 TI - Pathobiology of ALK-negative anaplastic large cell lymphoma. AB - The authors revise the concept of ALK-negative anaplastic large cell lymphoma (ALCL) in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated as well as the phenotypic, molecular and clinical characteristics. Finally, the biological rationale for possible innovative targeted therapies is presented. PMID- 22053282 TI - How does the NPM1 mutant induce leukemia? AB - NPM1 is the most frequently mutated gene in AML and the role of the NPM1 mutant in acute myeloid leukemia along with its leukemogenic potential are still under investigation.NPM1 genetic alterations can contribute to leukemogenesis through the direct oncogenic effect of the mutant protein and the concomitant loss of one functional allele. Npm1 loss determines tumor development in the mouse while in human NPM1 maps in a chromosomal region frequently loss in myelodysplastic syndrome (MDS). The NPM1 mutant cytoplasmic delocalization in leukemic blasts alters multiple cellular pathways through either loss or gain of function effects on different protein partners.Here we discuss the most relevant studies on the role of the NPM1 molecule in hematological malignancies and both in vitro and in vivo studies that are trying to elucidate the way by which the NPM1 mutation induces leukemia. PMID- 22053283 TI - Aplastic anemia: immunosuppressive therapy in 2010. AB - Acquired aplastic anemia (AA) is the typical bone marrow failure syndrome characterized by an empty bone marrow; an immune-mediated pathophysiology has been demonstrated by experimental works as well as by clinical observations. Immunusuppressive therapy (IST) is a key treatment strategy for aplastic anemia; since 20 years the standard IST for AA patients has been anti-thymocyte globuline (ATG) plus cyclosporine A (CyA), which results in response rates ranging between 50% and 70%, and even higher overall survival. However, primary and secondary failures after IST remain frequent, and to date all attempts aiming to overcome this problem have been unfruitful. Here we review the state of the art of IST for AA in 2010, focusing on possible strategies to improve current treatments. We also discuss very recent data which question the equality of different ATG preparations, leading to a possible reconsideration of the current standards of care for AA patients. PMID- 22053284 TI - Fanconi anemia - learning from children. AB - Fanconi Anemia (FA) is a rare autosomic recessive and X-linked disease with chromosomal instability after exposure to crosslinking agents as the hallmark. Clinical features of FA are somatic malformations, progressive bone marrow failure and cancer proneness, however there is wide clinical heterogeneity. The symptom most frequently and early associated with morbidity and mortality is progressive pancytopenia in the first decade of life although acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) can appear before aplastic anemia. Squamous cell carcinoma (SCC) of the head-neck, intestinal or genital tract has a very high incidence in FA and can appear at young age. This paper will focus on treatment of bone marrow failure in FA. PMID- 22053285 TI - Severe congenital neutropenia, a genetically heterogeneous disease group with an increased risk of AML/MDS. AB - OVER THE PAST DECADE, ENORMOUS PROGRESS HAS BEEN MADE IN THE UNDERSTANDING OF SEVERE CONGENITAL NEUTROPENIA (SCN), BY IDENTIFICATION OF SEVERAL CAUSAL GENE MUTATIONS: in ELANE, GFI1, HAX1, WAS and G3PC3. SCN is a preleukemic condition, independent of the genetic subtype. Acquired CSF3R mutations are specific for SCN and are strongly associated with malignant progression. In this review, we describe the known genetic subtypes of SCN, their molecular basis and clinical presentation and summarize the available evidence on CSF3R mutations and monosomy 7 in malignant conversion. PMID- 22053286 TI - Developing an Institutional Informational Base and Bibliographical Clearinghouse. AB - Successful management and implementation of the diverse functions of the International Network of Person-Centered Medicine (INPCM) require a comprehensive and efficient informational base to advance quality of patient care though timely and rapid distribution of knowledge via publications, conferences, and education programs in concert with catalyzing research through systematic efficient data acquisition, storage, retrieval, and analysis. This study describes the structure and functions of the proposed INPCM's information system. PMID- 22053287 TI - Arf6-dependent intracellular trafficking of Pasteurella multocida toxin and pH dependent translocation from late endosomes. AB - The potent mitogenic toxin from Pasteurella multocida (PMT) is the major virulence factor associated with a number of epizootic and zoonotic diseases caused by infection with this respiratory pathogen. PMT is a glutamine-specific protein deamidase that acts on its intracellular G-protein targets to increase intracellular calcium, cytoskeletal, and mitogenic signaling. PMT enters cells through receptor-mediated endocytosis and then translocates into the cytosol through a pH-dependent process that is inhibited by NH(4)Cl or bafilomycin A1. However, the detailed mechanisms that govern cellular entry, trafficking, and translocation of PMT remain unclear. Co-localization studies described herein revealed that while PMT shares an initial entry pathway with transferrin (Tfn) and cholera toxin (CT), the trafficking pathways of Tfn, CT, and PMT subsequently diverge, as Tfn is trafficked to recycling endosomes, CT is trafficked retrograde to the ER, and PMT is trafficked to late endosomes. Our studies implicate the small regulatory GTPase Arf6 in the endocytic trafficking of PMT. Translocation of PMT from the endocytic vesicle occurs through a pH-dependent process that is also dependent on both microtubule and actin dynamics, as evidenced by inhibition of PMT activity in our SRE-based reporter assay, with nocodazole and cytochalasin D, respectively, suggesting that membrane translocation and cytotoxicity of PMT is dependent on its transfer to late endosomal compartments. In contrast, disruption of Golgi-ER trafficking with brefeldin A increased PMT activity, suggesting that inhibiting PMT trafficking to non-productive compartments that do not lead to translocation, while promoting formation of an acidic tubulovesicle system more conducive to translocation, enhances PMT translocation and activity. PMID- 22053289 TI - "Asia Pacific Allergy": A new leap forward. PMID- 22053288 TI - Targeting the tumor microenvironment in cancer: why hyaluronidase deserves a second look. AB - Increased extracellular matrix (ECM) deposition is a characteristic observed in many solid tumors. Increased levels of one ECM component-namely, hyaluronan (HA) leads to reduced elasticity of tumor tissue and increased interstitial fluid pressure. Multiple initial reports showed that the addition of hyaluronidase (HYAL) to chemotherapeutic regimens could greatly improve efficacy. Unfortunately, the bovine HYAL used in those studies was limited therapeutically by immunologic responses to treatment. Newly developed recombinant human HYAL has recently been introduced into clinical trials. In this article, we describe the role of HA in cancer, methods of targeting HA, and clinical studies performed to date, and we propose that targeting HA could now be an effective treatment option for patients with many different types of solid tumors. PMID- 22053291 TI - Immunoglobulin E in health and disease. AB - The discovery of immunoglobulin E (IgE) was a breakthrough in the field of Allergy and Immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. Apart from allergic diseases, IgE is involved in pathogenesis of other disorders. Much controversy exists about the control of total IgE (tIgE) levels and allergen-specific IgE (sIgE) profiles in allergic individuals. This review aims at giving a comprehensive overview of IgE molecule and discussing the issues related to its importance in clinical setting. PMID- 22053293 TI - Impact of chronic urticaria on the quality of life in Australian and Sri Lankan populations. AB - BACKGROUND: Chronic idiopathic urticaria (CIU) has a significant impact on patients' quality of life. OBJECTIVE: The purpose of this study is to assess that impact and to compare differences by culture, gender, age or duration of treatment. METHODS: We used the modified chronic urticaria quality of life questionnaire, consisting of 15 questions. Over the course of 6 months, patients attending Immunology clinics at Campbelltown Hospital and private rooms in Australia and at the faculty of Medicine, University of Kelaniya in Sri Lanka were asked to fill out the questionnaires. We have obtained the data from 125 patients (43 Australian vs. 82 Sri Lankan). There were significantly more female patients (P < 0.01). The data was analysed using SAS. RESULTS: Overall, patients were affected mostly by itch and wheals and least affected by the side effects of treatments. Sri Lankan populations were more affected by wheals and by interference on activities, mood and food choices but were less affected by tiredness due to sleep disturbances (P < 0.01). Females were more affected by sleep disturbance (P < 0.05) while those older than 40 years of age were more impacted by tiredness and by the side effects from medications (P < 0.05), though the complaints themselves were mild. Those who suffered from CIU for more than 1 year were more affected by wheal, tiredness and irritability (P <= 0.05). CONCLUSION: The questionnaire highlighted some differences between patients attending Australian versus Sri Lankan outpatients. Significant differences were found in one third of parameters which include mood, sleep, daily activities and food choices. PMID- 22053292 TI - Clinical characteristics and long-term outcomes related to sputum eosinophilia in Korean asthmatics. AB - BACKGROUND: Bronchial asthma is usually associated with high sputum eosinophil levels. However, recent reports have suggested the importance of noneosinophilic asthma (NEA) as a distinct phenotype of asthma. OBJECTIVE: The aim of this study was to evaluate clinical significance of sputum eosinophilia and long-term treatment outcomes related to sputum eosinophilia in Korean asthmatics. METHODS: A total of 201 steroid-naive asthmatics who had undergone induced sputum analysis at baseline were selected from the Cohort for Reality and Evolution of Adult Asthma study population. Clinical evaluation, spirometry, a skin-prick test, a methacholine bronchial provocation test, and sputum eosinophil analysis were performed initially, and patients received the treatment recommended by the Global Initiative for Asthma. Lung function was evaluated every 6 months, and 53 patients completed 24 months of regular follow-up visits. Sputum eosinophilia was defined as a sputum eosinophil count of >3%. RESULTS: Of the 201 steroid-naive asthmatics, 97 patients had NEA and 104 had eosinophilic asthma (EA). Only 52% of steroid-naive asthmatic subjects had elevated baseline sputum eosinophil levels. A higher percentage of sputum eosinophils was associated with a lower PC20 (r = 0.193; p = 0.009, Spearman correlation), but not with forced expiratory volume in one second (FEV1) (r = 0.045; p = 0.525). During the 24-month study period, the percentage change of FEV1 was significantly lower in the NEA group than in the EA group at 6, 12, 18, and 24 months (p < 0.05). The NEA group, unlike the EA group, showed no significant improvement in FEV1 at 6, 12, 18, or 24 months (p > 0.05). CONCLUSION: A higher sputum eosinophil percentage was correlated with a higher airway hyperresponsiveness. Compared with EA patients, NEA patients had poor treatment outcomes in the 2-year follow-up of a Korean asthma cohort population. PMID- 22053290 TI - Clinical applications of drug desensitization in the Asia-Pacific region. AB - Drug desensitization is the induction, within hours to days, of a temporary state of tolerance to a drug which the patient has developed a hypersensitivity reaction to. It may be used for IgE and non-IgE mediated allergic reactions, and certain non-allergic reactions. The indication for desensitization is where no alternative medications are available for the treatment of that condition, and where the benefits of desensitization outweigh the risks. Desensitization is a therapeutic modality for drug allergy (similar to allergen specific immunotherapy for allergic rhinitis and insect venom anaphylaxis). In contrast, the drug provocation test is a diagnostic modality used to confirm or refute the diagnosis of drug allergy. This review discusses the clinical applications of desensitization for the treatment of common infectious, metabolic and cardiovascular diseases, and oncological conditions in the Asia-Pacific region. PMID- 22053294 TI - Prolonged bedtime bottle feeding and respiratory symptoms in infants. AB - BACKGROUND: Infants with chronic respiratory symptoms should be evaluated thoroughly because there are various causes which are different from those of children and adolescents. OBJECTIVE: This study was designed to investigate the relationship between chronic respiratory symptoms and bedtime bottle feeding in infants after the age of 6 months. METHODS: We conducted a prospective study that included 44 infants who presented with respiratory symptoms for more than 8 weeks and also had been bottle-fed during bedtime even after 6 months of age. The infants were divided into 2 groups; infants who discontinued bedtime bottle feeding and those who did not. Respiratory symptom scores were graded with a four point scale at 0, 1, 2 and 3 months, and were compared between the 2 groups. RESULTS: Twenty eight infants (63.6%) stopped being bottle-fed during bedtime and 16 infants (36.4%) were still bottle-fed. The respiratory symptom scores were significantly decreased in infants who stopped bedtime bottle feeding (p = 0.0003). CONCLUSION: It is suggested that prolonged bedtime bottle feeding might be one of the causes of chronic respiratory symptoms in infants. PMID- 22053295 TI - Irritable bowel syndrome - An inflammatory disease involving mast cells. AB - Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder that is the presence of symptoms in the absence of demonstrable pathological abnormalities. In recent times, low grade inflammatory infiltrates in both the small and large bowel of some patients with IBS - often rich in mast cells, along with serological markers of low grade inflammation have focussed attention on IBS as an inflammatory disease. The observation that mast cells often lie in close association to enteric neurons, and in-vitro and in-vivo animal studies demonstrating that mast cell mediators may influence enteric motility provides a biologically plausible causal mechanism in IBS. Pilot studies on patients with IBS using the mast cell stabiliser sodium cromoglycate ('proof of concept') have been encouraging. The essential question remains why mast cells infiltrate the bowel of IBS patients. A disturbance of the 'brain-gut axis' is the current favoured hypothesis, whereby childhood stress or psychiatric comorbidity act via neuro-immune mechanisms to modulate low grade inflammation. An alternative hypothesis is that food allergy may be responsible. Serum specific IgE, and skin prick tests are not elevated in IBS patients, suggesting type 1 IgE mediated food allergy is not the cause. However questionnaire based studies indicate IBS patients have higher rates of atopic disease, and increased bronchial reactivity to methacholine has been demonstrated. In this review, we highlight the potential role of mast cells in IBS, and current and future research directions into this intriguing condition. PMID- 22053296 TI - Hypersensitivity manifestations to the fruit mango. AB - The objectives of this study are 1) To review the published data and document the current knowledge on allergic manifestations to the fruit mango 2) To highlight the two distinct clinical presentations of hypersensitivity reactions caused by mango 3) To discuss the role of cross-reactivity 4) To increase awareness of potentially life threatening complications that can be caused by allergy to mango. An extensive search of the literature was performed in Medline/PubMed with the key terms "mango", "anaphylaxis", "contact dermatitis", "cross-reactivity", "food hypersensitivity", "oral allergy syndrome" and "urticaria". The bibliographies of all papers thus located were searched for further relevant articles. A total of 17 reports describing 22 patients were documented, including ten patients with immediate hypersensitivity reaction and twelve patients with delayed hypersensitivity reaction to mango. Ten of these patients (four with immediate reaction; six with delayed reaction) were from geographical areas cultivating mango, whereas twelve patients (six with immediate reaction; six with delayed reaction) were from the countries where large scale mango cultivation does not occur. The clinical features, pathogenesis and diagnostic modalities of both these presentations are highlighted. The fruit mango can cause immediate and delayed hypersensitivity reactions, as also "oral allergy syndrome". Although rare, it can even result in a life threatening event. Reactions may even occur in individuals without prior exposure to mango, owing to cross reactivity. It is imperative to recognize such a phenomenon early so as to avoid potentially severe clinical reactions in susceptible patients. PMID- 22053297 TI - Early intervention in the management of atopic dermatitis. PMID- 22053298 TI - A proposal: Atopic Dermatitis Organizer (ADO) guideline for children. AB - Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder in children, with a worldwide cumulative prevalence in children of 8-20%. The number of AD patients is beyond the level that can be dealt with at clinics and it is time to make an effort to reduce the number of AD patients in the community. Thus, caregivers and all persons involved with AD management, including health care providers, educators, technologists and medical policy makers, should understand the development and the management of AD. Although a number of guidelines such as Practical Allergy (PRACTALL) report have been developed and used, community understanding of these is low. This is probably because there are still remarkable differences in management practices between specialists and between countries and most of the reported guidelines have been prepared for physicians. From the viewpoint of providing a basis for a multidisciplinary team approach, easily comprehensible guidelines for organizing treatment of AD, i.e. an Atopic Dermatitis Organizer (ADO), are required. guidelines should be simple and well organized. We suggest an easy approach with a new classification of AD symptoms into early and/or progressive lesions in acute and/or chronic symptoms. The contents of this ADO guideline basically consist of 3 steps approaches: conservative management, topical anti-inflammatory therapy, and systemic anti inflammatory therapy. PMID- 22053299 TI - Current status of atopic dermatitis in Japan. AB - Atopic dermatitis (AD) is a common, chronic or chronically relapsing, severely pruritic, eczematous skin disease. AD is the second most frequently observed skin disease in dermatology clinics in Japan. Prevalence of childhood AD is 12-13% in mainland Japan; however, it is only half that (about 6%) in children from Ishigaki Island, Okinawa. Topical steroids and tacrolimus are the mainstay of treatment. However, the adverse effects and emotional fear of long-term use of topical steroids have induced a "topical steroid phobia" in patients throughout the world. Undertreatment can exacerbate facial/periocular lesions and lead to the development of atopic cataract and retinal detachment due to repeated scratching/rubbing/patting. Overcoming topical steroid phobia is a key issue for the successful treatment of AD through education, understanding and cooperation of patients and their guardians. PMID- 22053300 TI - The role of allergic risk and other factors that affect the occurrence of atopic dermatitis in the first 6 months of life. AB - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammation of the skin that often appears in early childhood. The manifestation is related to the tendency towards T helper 2 cytokine immune responses (interleukin (IL)-4, IL-5). Genetic factors are suggested to play important roles in AD, and it can be transmitted to newborns, increasing their risk of developing allergies. OBJECTIVE: To determine the association between cord-blood cytokine levels (IL-5, interferon (IFN) gamma), cord-blood total immunoglobulin E (IgE) level, perinatal environmental exposure, and the risks of allergy as well as the development of AD in the first 6 months of life. METHODS: A 6-month cohort study with a nested case-control within was conducted on newborns in Jakarta from December 2008 until May 2009. After the umbilical cord blood samples were taken and stored, subjects were followed up monthly until 6 months old. The occurrence of AD and lifestyle or environmental exposures were recorded. The allergic risk was determined using a modified pediatric allergy immunology work groups scoring system based on allergic history (allergic rhinitis, asthma, AD) in the family. The levels of IL 5 and IFN-gamma were measured using ELISA and total IgE by CAP system FEIA. Multivariate analysis was used to evaluate risk factors. RESULTS: This study was conducted on 226 subjects. The incidence of AD was 16.4%; of those, 59% had low risk allergy, 38.5% moderate, and 2% high risk. AD mostly occurred at the age of 1 month (57%). Cord blood samples were examined in 37 subjects with AD and 51 without AD; of those, 25% showed high levels of total IgE (>1.2 IU/uL), and 51% showed normally-distributed high absorbance IL-5 values (>=0.0715, absolute value was undetected). The increased level of IL-5 was directly proportional to IgE. High absorbance IFN-gamma values (>=0.0795, absolute value = 18.681 pg/uL) were observed in 52% of subjects. CONCLUSION: The associations between the risk of allergy in the family, cord-blood total IgE, IL-5, IFN levels, and some perinatal environmental exposure with AD in the first 6 months of life have not been established. PMID- 22053301 TI - Clinical features of the extrinsic and intrinsic types of adult-onset atopic dermatitis. AB - BACKGROUND: Most study concerning the prevalence and dermatological manifestations of the extrinsic and the intrinsic form of atopic dermatitis (AD) were performed in children and adult AD related to the early-onset AD extending to adult life. Adult-onset AD is a subgroup of AD. Apart from the typical eczematous flexural distribution pattern of AD, this group may also have nontypical morphology and localization. OBJECTIVE: The purpose of this study was to compare the clinical and diagnostic features of Thai patients with extrinsic and intrinsic type of adult-onset AD. METHODS: We retrospectively studied case records of patients diagnosed as adult-onset AD at the skin allergy clinic, Department of Dermatology, Siriraj Hospital, Mahidol University, Bangkok, Thailand from June, 2006 to May, 2008. The diagnosis of AD was made according to the criteria of Hanifin and Rajka and the severity of AD in each patient were assessed using the eczema area and severity index and the Rajka and Langeland score. RESULTS: Fifty six patients were enrolled. Eighty-seven percent of patients were extrinsic AD (eAD). Females predominated in both groups. Patients with eAD more commonly had typical lichenified/exudative eczematous lesions, especially on the antecubital and popliteal areas, when compared with patients with intrinsic AD (iAD). Nummular and follicular lesions were more commonly seen in iAD group than the eAD group. The most common area of involvement in the iAD was non-flexural area, followed by flexural area and extensor area. The severity of both iAD and eAD did not show a significant difference. CONCLUSION: The eAD type of adult-onset AD was more common than the iAD type. Patients with eAD frequently had flexural lichenification whereas the iAD group tended to have nonflexural area involvement. The severity of both iAD and eAD did not show a significant difference. PMID- 22053302 TI - The clinical effects of hospitalization in a low pollutant room on atopic dermatitis. AB - BACKGROUND: Environmental pollutants are thought to be one of major triggers of atopic dermatitis (AD). OBJECTIVE: We attempted to evaluate the clinical effects of environment with low indoor pollutant levels on AD management. METHODS: Fifty one children (mean age 1.7 years) with moderate to severe AD who failed to show improvement with conventional management were recruited. Disease severity was assessed by SCORAD (Scoring of AD) indices. They were admitted in a low pollutant oom for 3-4 days (mean 3.3 days) which was designed to keep low levels of dust, house dust mites, micro-organisms, and indoor air pollutants such as total volatile organic compounds (TVOCs), particulate matter (PM), and so on. Air pollutant levels in the low pollutant room were lower than primary standards defined by the Korean Ministry of Environment. we compared disease severity on admission and after discharge, and the pollutant levels of each patient's home and low pollutant room. RESULTS: The SCORAD was significantly reduced from 42.0 +/- 11 .5 to 29.8 +/- 8.9 (p < 0.001) by management in a low pollutant room. PM(2.5), PM(10), formaldehyde, TVOCs, carbon dioxide, bacterial suspensions, and indoor molds were significantly higher in the patient's home than low pollutant room. Out of 29 patients who deteriorated after discharge to their home, 8 patients were admitted again, and their SCORAD was rapidly decreased from 53.1 +/ 16.2 to 39.2 +/- 9.8 (p = 0.036). CONCLUSION: Indoor air pollutants are likely to affect AD in susceptible individuals. Environmental control to lower indoor air pollutant levels might be necessary for better management of AD in some patients. PMID- 22053303 TI - Introduction to bioinformatics: sequencing technology. AB - Bioinformatics, the study of integrating high throughput biological data and statistical model through intensive computation, has been attracting great interest in recent times and Sequencing is at the very center of it. The large amount of information obtained from sequencing has deepened our understanding and fundamental knowledge of organisms. This review will aim to provide a brief summary of new sequencing technology, current issues, and projects focused on medical applications. The article is organized in three parts. Part I explains common terminologies and background of sequencing technology, and Part II compares distinct features of currently available platforms. Part III contains applications in various medical fields. PMID- 22053304 TI - Vogt-Koyanagi-Harada disease in an 8-year-old boy. AB - Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disease involving pigmented tissue in eyes, auditory system, skin, and central nervous system. The pathogenesis is a result of T cell lymphocyte reaction against melanocyte component, tyrosinase and tyrosinase-related protein. This disease uniquely affected pigmented race in Asia and native America, mostly women aged 20-50. We reported an 8-years-old boy complained for visual disturbance since 6 weeks prior admission. Two years earlier, the parents noted the patient eyes were looked red when photographed (suggesting a dilated pupil) preceded by whitened on the right forehead and nose and whitened hair, eyebrow and eyelashes. The examination showed a vitiligo and skin atrophy on right frontal and right nasal, poliosis on the eyebrows, eyelids and hair. The diameter of right pupil was 8 mm, with a paresis on 3rd, 4th, 6th, and 9th nerves. Fundus examination revealed sunset glow appearance. The visual acuity on the right eye: 2/60, left eye: 1-0. There's positive serology for antitoxoplasma IgG, anti Rubella IgG, anti CMV IgG. The patient was diagnosed with a VKH disease and then prescribed with methylprednisolone 1 mg/kg/day. The patient also had further follow up with dermatovenerologist and ophthalmologist. The eye examination revealed an improvement on right eye panuveitis, with a remaining keratic precipitate in the endothelium, and minimal flare and cell on the anterior chamber. ENT consultation revealed no ear inflammation or hearing disturbance. PMID- 22053305 TI - Current trends in upper airways and ocular allergic inflammation. PMID- 22053306 TI - Ocular allergy in the Asia Pacific region. AB - Allergic conjunctivitis (AC) represents a spectrum of disorders, comprising seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC) and giant papillary conjunctivitis. Of these ocular allergy types, SAC and PAC are the most common.The most striking difference within this group of ocular diseases is that SAC and PAC remain self-limited without ocular surface damage, while AKC and VKC can compromise the cornea, causing ulcers and scarring and can ultimately lead to vision loss. Data on AC in the Asia Pacific is scarce however some understanding of prevalence of the condition has been obtained from the International Study of Asthma and Allergies in Childhood (ISAAC) studies and more recently from the Allergies in Asia Pacific study as well as some information from individual country surveys. Unfortunately none of this data has been collected using validated survey instruments specifically designed for AC. Surveys such as ISAAC have been predominantly concerned with respiratory allergic symptoms with questions added that incorporate some ocular symptoms. These questionnaires do not detect individuals who may have AC in the absence of allergic rhinitis. Using hospital ophthalmology outpatient populations for prevalence studies of ocular allergy immediately introduces a bias towards the more severe, complex forms of the condition as patients with the milder forms of SAR and PAR will rarely present to a hospital outpatient clinic. There is a real need for the development of validated questionnaires specifically addressing ocular allergy. There are no widely accessible studies examining prevalence of the complex forms of ocular allergy (AKC, VKC) in Asia Pacific region. This review will provide an overview of ocular allergy, its classification, clinical presentation and differential diagnosis, and will also discuss what is known about the epidemiology of ocular allergy in the Asian Pacific region. PMID- 22053307 TI - Rhinitis in children less than 6 years of age: current knowledge and challenges. AB - Rhinitis is a disease of the upper airway characterized by runny and/or blocked nose and/or sneezing. Though not viewed as a life threatening condition, it is also recognized to impose significant burden to the quality of life of sufferers and their caretakers and imposes an economic cost to society. Through a PubMed online search of the literature from 2006 to September 2011, this paper aims to review the published literature on rhinitis in young children below the age of 6 years. It is apparent from epidemiology studies that rhinitis in this age group is a relatively common problem. The condition has a heterogenous etiology with classification into allergic and non-allergic rhinitis. Respiratory viral infections may play a role in the pathogenesis of long standing rhinitis, but definitive studies are still lacking. Treatment guidelines for management are lacking for this age group, and is a significant unmet need. Although the consensus is that co-morbidities including otitis media with effusion, adenoidal hypertrophy and asthma, are important considerations of management of these children. Pharmacotherapy is limited for young children especially for those below the age of 2 years. This review underscores the lack of understanding of rhinitis in early childhood and therefore the need for further research in this area. PMID- 22053308 TI - Sublingual immunotherapy in allergic rhinitis. AB - Current treatment options for allergic rhinitis (AR) include allergen avoidance and environmental control, pharmacotherapy, nasal surgery and immunotherapy. Among these, immunotherapy is the only therapeutic option that modifies fundamental immunologic mechanism by inducing desensitization. Specific allergen immunotherapy has been used for 1 century since 1911 and subcutaneous immunotherapy (SCIT) has been demonstrated to be effective in asthma and AR. However, SCIT has several disadvantages such as inconvenience, invasiveness and potentially severe systemic reactions. Thus, sublingual immunotherapy (SLIT) has recently received much attention around the world as a treatment for AR and is now widely used to replace the subcutaneous route. SLIT has recently been introduced in Korea and is now available for AR treatment in the Asia-Pacific region. This review offers better understanding of SLIT for AR by summarizing published articles and our previous works regarding proposed mechanisms, indication and efficacy, safety and adverse events, and compliance. PMID- 22053309 TI - Allergic Aspergillus sinusitis and its association with allergic bronchopulmonary aspergillosis. AB - Allergic Aspergillus sinusitis (AAS) is a three decade old clinicopathologic entity in which mucoid impaction akin to that of allergic bronchopulmonary aspergillosis (ABPA) occurs in the paranasal sinuses. Features such as radiographic evidence of pansinusitis, passage of nasal plugs and recurrent nasal polyposis in patients with an atopic background is suggestive of AAS. Histopathlogic confirmation from the inspissated mucus is a sine qua non for the diagnosis. Heterogeneous densities on computed tomography of the paranasal sinuses are caused by the 'allergic mucin' in the sinuses. Many patients give a history of having undergone multiple surgical procedures for symptomatic relief. The current approach to treatment appears to include an initial surgical debridement followed by postoperative oral corticosteroids for long durations. Although both ABPA and AAS are classified as Aspergillus-related hypersensitivity respiratory disorders, their co-occurrence appears to be an infrequently recognised phenomenon. This could perhaps be attributed to the fact that these two diseases are often treated by two different specialties. A high index of suspicion is required to establish the diagnoses of ABPA and AAS. All patients with asthma and/or rhinosinusitis along with sensitisation to Aspergillus antigens are at an increased risk of developing ABPA and/or AAS. ABPA must be excluded in all patients with AAS and vice versa. Early diagnosis and initiation of appropriate therapy could plausibly alter the course of the disease processes and prevent the possible development of long term sequelae. PMID- 22053310 TI - Investigation of the antiallergic activity of olopatadine on rhinitis induced by intranasal instillation of antigen in sensitized rats using thermography. AB - BACKGROUND: The main symptoms of allergic rhinitis (AR) are sneezing, rhinorrhea and nasal obstruction. It was reported that the nasal skin temperature after intranasal administration of histamine or grass pollen rose. In patients with AR, the levels of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) have increased in nasal fluids and mucosa. OBJECTIVE: The present study were to determine the temperature changes of the nose in rat allergic rhinitis model, and if olopatadine, an antiallergic agent with histamine H1 receptor antagonistic action, proved to be effective, were studied the productions of NGF and VEGF in nasal lavage fluids (NALF). In the present study, we used ovalbumin (OVA)-sensitized rats as an animal model of nasal allergy and examined the effects of olopatadine on the skin temperature of the nose area, and the productions of NGF and VEGF in NALF. METHODS: The temperature changes of the nose area were carried out with thermo tracer in rat passively sensitized with OVA antiserum. The numbers of sneezing episodes were counted and, NGF and VEGF levels in NALF were examined using the specific ELISA. RESULTS: In OVA-sensitized rats, the number of sneezing episodes increase and the nasal skin temperature rise were provoked after OVA challenge. The levels of NGF and VEGF in NALF also were increased. Olopatadine reduced the increased frequency of sneezing and the nasal skin temperature rise. It also inhibited the increased NGF and VEGF productions in NALF. CONCLUSION: The nasal skin temperature after OVA challenge rose even in OVA-sensitized rats. These results suggest that the suppression of the increased NGF and VEGF levels might partially be involved in the improvement of allergy like behavior (sneezing and nasal skin temperature rise) by the treatment of olopatadine. PMID- 22053311 TI - Association of house dust mite-specific IgE with asthma control, medications and household pets. AB - BACKGROUND: Evidence is conflicting regarding the effectiveness of creating a low allergen environment or reducing allergen exposure to control asthma exacerbations. OBJECTIVE: This study determined the association of house dust mite (HDM)-specific IgE levels with asthma symptom control, selected medications, family history of allergic disease, and exposure to second-hand smoke and household pets. METHODS: Serum samples from 102 doctor-diagnosed allergic asthma patients and 100 non-atopic controls were subjected to enzyme-linked immunosorbent assay using the HDM species Dermatophagoides pteronyssinus (Dp), Dermatophagoides farinae (Df), and Blomia tropicalis (Bt) allergens. Point biserial correlation coefficient, Pearson R correlation, and logistic regression analyses were used to determine association of HDM-specific IgE levels with the abovementioned variables. RESULTS: Of the 102 cases, 38.24%, 47.06%, and 33.33% were sensitized to Bt, Df, and Dp, respectively. Sensitized patients showed greater probability [Bt (OR = 1.21), Df (OR = 1.14), and Dp (OR = 1.35)] to manifest symptoms than those who were not. Obtained p-values [Bt (p = 0.73), Df (p = 0.83), and Dp (p = 0.59)], however, proved that HDM-specific IgE levels had no significant contribution in predicting or explaining occurrence of asthma symptoms. Bt- and Df-specific IgEs showed moderately weak but significant relationship with bambuterol HCl and expectorant, respectively. Patients currently on said medications registered higher HDM-specific IgE levels than those who were not. No significant correlation between IgE levels and family history of allergic disease or with exposure to second-hand smoke was seen. Dp specific IgE levels of patients exposed to household pets were significantly lower compared to those without exposure. CONCLUSION: This study proves that sensitization to Bt, Df, and Dp allergens is not significantly associated with asthma symptoms and control. Although cases were shown to be sensitized to HDMs, their current medications were at least effective in controlling their asthma symptoms. PMID- 22053312 TI - Genetic predisposition for atopy and allergic rhinitis in the Singapore Chinese population. AB - The prevalence of allergic diseases is high globally, but especially in developed countries, with one in five to one in four individuals affected worldwide. The World Health Organization's "Allergic Rhinitis and its Impact on Asthma 2008 Update" guidelines stated explicitly that over 600 million patients from all countries, all ethnic groups and all ages suffer from allergic rhinitis (AR). There are clear evidences to support the concept that allergic diseases are influenced by genetic predisposition and environmental factors. The genetic basis of AR has been evaluated more intensively in the recent 10-20 years. Advances in technology and statistical methods, such as genome-wide association studies (GWAS) have enabled millions of single nucleotide polymorphisms (SNPs) to be genotyped at rapid pace and for less cost. However these studies have not yet answered the entire heritability profile of the disease. Additionally, environmental influences on these genetic variants cannot be discounted. Hence these allergic diseases must be evaluated as a complex interplay between genetic and environmental factors. This review focuses on the genetic basis of AR, with special emphasis on studies performed in Singapore. Candidate gene based studies and GWAS performed in Singapore cohorts have been discussed to suggest how these diseases could be understood better in a Singapore context which is still applicable to research in AR globally. PMID- 22053313 TI - Overview on the pathomechanisms of allergic rhinitis. AB - Allergic rhinitis a chronic inflammatory disease of the upper airways that has a major impact on the quality of life of patients and is a socio-economic burden. Understanding the underlying immune mechanisms is central to developing better and more targeted therapies. The inflammatory response in the nasal mucosa includes an immediate IgE-mediated mast cell response as well as a latephase response characterized by recruitment of eosinophils, basophils, and T cells expressing Th2 cytokines including interleukin (IL)-4, a switch factor for IgE synthesis, and IL-5, an eosinophil growth factor and on-going allergic inflammation. Recent advances have suggested new pathways like local synthesis of IgE, the IgE-IgE receptor mast cell cascade in on-going allergic inflammation and the epithelial expression of cytokines that regulate Th2 cytokine responses (i.e., thymic stromal lymphopoietin, IL-25, and IL-33). In this review, we briefly review the conventional pathways in the pathophysiology of allergic rhinitis and then elaborate on the recent advances in the pathophysiology of allergic rhinitis. An improved understanding of the immune mechanisms of allergic rhinitis can provide a better insight on novel therapeutic targets. PMID- 22053314 TI - Human seminal plasma allergy: successful pregnancy after prophylactic anti histamine treatment. AB - Human seminal plasma allergy is a rare phenomenon. Its clinical manifestations are diverse, and range from mild local pruritus to fatal anaphylaxis. Treatment varies with severity of the reactions: abstinence, condom usage or immunotherapy (subcutaneous or intravaginal) with seminal fluid. Local allergic reactions can be managed by prophylactic use of antihistamines or local cromolyn cream. A 33 year-old female visited the Asthma and Allergy Clinic in Seoul National University Bundang Hospital for the recurrent generalized urticarial reactions after sexual intercourse. She had been suffering from asthma, allergic rhinoconjunctivitis and atopic dermatitis for 10 years. She gave birth to a baby 6 months ago and no problem before. However, recently she began to recognize unexpected generalized urticaria that occurred after the sexual intercourse with husband. She wanted to have the second baby but hesitated because of the recurrent symptoms after the intercourse. She showed positive response to skin prick test with her husband's seminal fluid. The IgE-binding components were 15, 22, 28, and 35 kDa. Considering her moderate cutaneous reactions, we decided to try prophylactic treatments with oral anti-histamine one hour before sexual intercourse. She did not experience urticarial reactions with intercourse while oral anti-histamine was administered in advance. Finally, treatment outcome was successful, and the couple successfully gave birth to their second baby. We suppose that prophylactic antihistamine may be also applied in seminal plasma allergy patients if systemic reactions are limited to mild to moderate generalized urticaria. PMID- 22053315 TI - Comparison of range of commercial or primary care led weight reduction programmes with minimal intervention control for weight loss in obesity: lighten Up randomised controlled trial. AB - OBJECTIVE: To assess the effectiveness of a range of weight management programmes in terms of weight loss. DESIGN: Eight arm randomised controlled trial. SETTING: Primary care trust in Birmingham, England. PARTICIPANTS: 740 obese or overweight men and women with a comorbid disorder identified from general practice records. INTERVENTIONS: Weight loss programmes of 12 weeks' duration: Weight Watchers; Slimming World; Rosemary Conley; group based, dietetics led programme; general practice one to one counselling; pharmacy led one to one counselling; choice of any of the six programmes. The comparator group was provided with 12 vouchers enabling free entrance to a local leisure (fitness) centre. MAIN OUTCOME MEASURES: The primary outcome was weight loss at programme end (12 weeks). Secondary outcomes were weight loss at one year, self reported physical activity, and percentage weight loss at programme end and one year. RESULTS: Follow-up data were available for 658 (88.9%) participants at programme end and 522 (70.5%) at one year. All programmes achieved significant weight loss from baseline to programme end (range 1.37 kg (general practice) to 4.43 kg (Weight Watchers)), and all except general practice and pharmacy provision resulted in significant weight loss at one year. At one year, only the Weight Watchers group had significantly greater weight loss than did the comparator group (2.5 (95% confidence interval 0.8 to 4.2) kg greater loss,). The commercial programmes achieved significantly greater weight loss than did the primary care programmes at programme end (mean difference 2.3 (1.3 to 3.4) kg). The primary care programmes were the most costly to provide. Participants allocated to the choice arm did not have better outcomes than those randomly allocated to a programme. CONCLUSIONS: Commercially provided weight management services are more effective and cheaper than primary care based services led by specially trained staff, which are ineffective. Trial registration Current Controlled Trials ISRCTN25072883. PMID- 22053316 TI - What makes a weight loss programme successful? PMID- 22053318 TI - Repeat prescribing in general practice. PMID- 22053317 TI - Receptionist input to quality and safety in repeat prescribing in UK general practice: ethnographic case study. AB - OBJECTIVE: To describe, explore, and compare organisational routines for repeat prescribing in general practice to identify contributors and barriers to safety and quality. DESIGN: Ethnographic case study. SETTING: Four urban UK general practices with diverse organisational characteristics using electronic patient records that supported semi-automation of repeat prescribing. PARTICIPANTS: 395 hours of ethnographic observation of staff (25 doctors, 16 nurses, 4 healthcare assistants, 6 managers, and 56 reception or administrative staff), and 28 documents and other artefacts relating to repeat prescribing locally and nationally. MAIN OUTCOME MEASURES: Potential threats to patient safety and characteristics of good practice. METHODS: Observation of how doctors, receptionists, and other administrative staff contributed to, and collaborated on, the repeat prescribing routine. Analysis included mapping prescribing routines, building a rich description of organisational practices, and drawing these together through narrative synthesis. This was informed by a sociological model of how organisational routines shape and are shaped by information and communications technologies. Results Repeat prescribing was a complex, technology supported social practice requiring collaboration between clinical and administrative staff, with important implications for patient safety. More than half of requests for repeat prescriptions were classed as "exceptions" by receptionists (most commonly because the drug, dose, or timing differed from what was on the electronic repeat list). They managed these exceptions by making situated judgments that enabled them (sometimes but not always) to bridge the gap between the idealised assumptions about tasks, roles, and interactions that were built into the electronic patient record and formal protocols, and the actual repeat prescribing routine as it played out in practice. This work was creative and demanded both explicit and tacit knowledge. Clinicians were often unaware of this input and it did not feature in policy documents or previous research. Yet it was sometimes critical to getting the job done and contributed in subtle ways to safeguarding patients. Conclusion Receptionists and administrative staff make important "hidden" contributions to quality and safety in repeat prescribing in general practice, regarding themselves accountable to patients for these contributions. Studying technology-supported work routines that seem mundane, standardised, and automated, but which in reality require a high degree of local tailoring and judgment from frontline staff, opens up a new agenda for the study of patient safety. PMID- 22053319 TI - Production of monoclonal antibodies against fullerene C60 and development of a fullerene enzyme immunoassay. AB - The aim of the present study was to produce monoclonal anti-fullerene C(60) antibodies and to develop the enzyme immunoassay for the detection in the first use of free fullerene C(60) both in solutions and in multicomponent biological probes. The immunization of mice with the conjugate of fullerene C(60) carboxylic derivative with thyroglobulin synthesized by carbodiimide activation led to the production of eight clones of anti-fullerene antibodies. The specificity of the antibody-fullerene binding was confirmed. Indirect competitive enzyme-linked immunosorbent assay (ELISA) was developed for the determination of water-soluble protein-conjugated fullerene, the fullerene aminocaproic acid, fullerenol and for pristine fullerene in solution. To solubilize extremely hydrophobic free fullerene C(60) a specially selected water-organic mixture compatible with immunoassay was proposed. The detection limit of free fullerene C(60) in solution was 2 MUg L(-1). Fullerene C(60) was also detected by ELISA in organ homogenates of rats intraperitoneally or intragastrically administered with fullerene. To reduce the influence of biomatrices on the assay results a technique was developed for the biological sample pretreatment by the extraction of C(60) from bioprobe by toluene followed by the evaporation of toluene and dissolution of the fullerene-containing extract in the selected water-organic media. The ELISA procedure in the first use allowed the detection of fullerene C(60) in different tissues. PMID- 22053320 TI - The interplay of turn formation and hydrophobic interactions on the early kinetic events in protein folding. AB - While both turn formation and hydrophobic interactions play dominant roles in the initiation of protein folding, their individual contributions to the folding kinetics and to the structural stability of the protein still remain poorly understood. Here, we applied a photolabile linker to "cage" some important structural motifs, including both alpha-helices and beta-sheets, into their non native states. These "caged" structural motifs are then relaxed by laser-flash photolysis and their refolding events followed by photoacoustic calorimetry (PAC) and photothermal beam deflection (PBD). These experiments, combined with our previous results, revealed that spontaneous alpha-helix formation can occur extremely rapidly (10(8)-10(9) s(-1)) if the process is driven solely by turn formation followed by helix propagation. However, if sequestering of the side chains of hydrophobic amino acid residues participates in the refolding process, which may provide additional driving force beyond that afforded by turn formation alone, the refolding rate will be retarded, often by many orders of magnitude. This is usually the case in the formation of three-stranded beta-sheets (10(7) 10(8) s(-1)) and beta-hairpins (10(5)-10(6) s(-1)). Thus, we propose that proteins take advantage of the hierarchy of timescales associated with either turn formation, hydrophobic interactions, or global collapse of tertiary structure to accomplish the folding process in an orderly fashion, as these events are sufficiently separated in time and do not interfere with one another. PMID- 22053321 TI - Melting point suppression in new lanthanoid(III) ionic liquids by trapping of kinetic polymorphs: an in situ synchrotron powder diffraction study. AB - The complexes (N(4444))(3)[Ln(dcnm)(6)] (Ln = La-Nd, Sm; N(4444) = tetrabutylammonium) display a decrease in the melting point upon fast cooling from a melt, which is shown by in situ synchrotron based X-ray powder diffraction to be due to the formation of a second, less thermodynamically stable, polymorph. PMID- 22053322 TI - Metal-assisted salphen organic frameworks (MaSOFs) with high surface areas and narrow pore-size distribution. AB - The one-pot three component synthesis of metal containing microporous organic polymers with high BET surface areas is presented. The metal salphen units were built during the formation of the porous polymers. Selective gas adsorption depending on the metal ions is discussed. PMID- 22053323 TI - Homochirality beyond grinding: deracemizing chiral crystals by temperature gradient under boiling. AB - A single-chirality solid phase can be obtained in boiling solutions containing a racemic mixture of left- and right-handed enantiomorphous crystals due to dissolution-crystallization cycles induced by a temperature gradient. This phenomenon provides further insights into asymmetric amplification mechanisms under presumably prebiotic conditions. PMID- 22053324 TI - The effect of a Hill-Sachs defect on glenohumeral translations, in situ capsular forces, and bony contact forces. AB - BACKGROUND: Hill-Sachs defects have been associated with failed repairs for anterior shoulder instability. However, the biomechanical consequences of these defects are not well understood because of the complicated interaction between the passive soft tissue and bony stabilizers. HYPOTHESIS: The creation of a 25% Hill-Sachs defect would not significantly alter the glenohumeral translations but would increase the in situ forces in the glenohumeral capsule as well as the glenohumeral bony contact forces. STUDY DESIGN: Controlled laboratory study. METHODS: A robotic/universal force-moment sensor (UFS) testing system was used to apply joint compression (22 N) and an anterior or posterior load (44 N) to cadaveric shoulders (n = 9) with the skin and deltoid removed (intact) at 3 glenohumeral joint positions (abduction/external rotation): 0 degrees /0 degrees , 30 degrees /30 degrees , and 60 degrees /60 degrees (corresponds to 90 degrees /90 degrees of shoulder abduction/external rotation). A 25% bony defect on the posterolateral humeral head (defect) was then created in the most common position of anterior shoulder dislocation (90 degrees /90 degrees ), and the loading protocol was repeated. A nonparametric repeated-measures Friedman test with a Wilcoxon signed-rank post hoc test was performed to compare translations, in situ forces in the capsule, and bony contact forces between each state (P < .05). RESULTS: At 0 degrees /0 degrees , anterior translation significantly increased from 15.3 +/- 8.2 mm to 16.6 +/- 9.0 mm (P < .05) in response to an anterior load. At 30 degrees /30 degrees , anterior and posterior translations, respectively, significantly increased in response to both anterior (intact: 13.6 +/- 7.1 mm vs defect: 14.2 +/- 7 mm; P < .05) and posterior loads (intact: 15.7 +/- 5.8 mm vs defect: 17.7 +/- 5.1 mm; P < .05). In situ force in the capsule during anterior loading was increased in the defect state at both 60 degrees /60 degrees (intact: 38.9 +/- 14.4 N vs defect: 43.2 +/- 15.9 N; P < .05) and 30 degrees /30 degrees (intact: 39.6 +/- 13.8 N vs defect: 45.6 +/- 9.3 N; P < .05). The medial bony contact forces were also increased in the defect state at 30 degrees /30 degrees (intact: 25.0 +/- 13.8 N vs defect: 28.9 +/- 13.2 N; P < .05) during anterior loading. CONCLUSION: We believe that the stabilizing function of the intact capsule was the primary contributor to the finding of only small increases of anterior translation, capsule forces, and bony contact forces observed with a 25% Hill-Sachs defect in response to an anterior load. CLINICAL RELEVANCE: These findings imply that a 25% Hill-Sachs defect in isolation may not be responsible for recurrent instability if the function of the capsule is restored to the intact state and that the presence of the Hill-Sachs defect may be a marker for significant concomitant injury to the anterior glenoid rim. However, the small changes in these parameters may have long-term implications for the development of osteoarthritis. PMID- 22053333 TI - As an evolutionary biologist. Debashish Bhattacharya. PMID- 22053325 TI - Prevalence of musculoskeletal injuries in Swedish elite track and field athletes. AB - BACKGROUND: Little is known of injury patterns in track and field (athletics). Injury prevalence has been proposed as the most appropriate measure of the injury rate in sports where athletes are at risk for overuse problems. PURPOSE: To ascertain 1-year retrospective and current prevalence of injury in elite track and field athletes to help plan injury prevention programs for this sport. STUDY DESIGN: Descriptive epidemiology study. METHODS: Two hundred seventy-eight youth (16 years old) and adult athletes from an eligible study population of 321 athletes were included. RESULTS: The 1-year retrospective injury prevalence was 42.8% (95% confidence interval [CI], 36.9%-49.0%); the point prevalence was 35.4% (95% CI, 29.7%-41.4%). The diagnosis group displaying the highest injury prevalence was inflammation and pain in the gradual onset category (1-year prevalence, 20.9%; 95% CI, 16.2%-26.2%; and point prevalence, 23.2%; 95% CI, 18.4%-28.7%). A strong tendency for higher 1-year prevalence of 16.5% (95% CI, 12.2%-21.4%) than point prevalence of 8.5% (95% CI, 5.5%-12.5%) was recorded for sudden onset injuries in the diagnosis group sprain, strain, and rupture. The body region showing the highest injury prevalence was the knee and lower leg with 15.0% (95% CI, 11.0%-19.8%) 1-year prevalence and 13.7% (95% CI, 9.8%-18.3%) point prevalence, followed by the Achilles tendon, ankle, and foot/toe with 11.7% (95% CI, 8.2%-16.1%) 1-year prevalence and 11.4% (95% CI, 7.9%-15.8%) point prevalence. CONCLUSION: The injury prevalence is high among Swedish elite track and field athletes. Most of the injuries affect the lower extremities and are associated with a gradual onset. Although it is associated with a potential recall bias, the 1-year retrospective prevalence measure captured more sudden onset injuries than the point prevalence measure. Future prospective studies in track and field are needed to identify groups of athletes at increased risk. PMID- 22053334 TI - Why do people riot? PMID- 22053335 TI - Cyanosis. PMID- 22053336 TI - Imaging the patient with suspected pulmonary venous thromboembolism. PMID- 22053338 TI - The critically ill patient: identification and initial stabilization. PMID- 22053337 TI - An international collaborative study to establish the WHO 1st international standards for C1-inhibitor, plasma and concentrate. PMID- 22053339 TI - Layout. PMID- 22053340 TI - From lab bench to product catalog. PMID- 22053341 TI - Calcium regulates key components of vascular smooth muscle cell- derived matrix vesicles to enhance mineralization. PMID- 22053342 TI - Second messenger role for Mg(2+) in T-cell activation. PMID- 22053343 TI - Association of race and age with survival among patients undergoing dialysis: racial differences on many levels. PMID- 22053344 TI - Gametes from stem cells. PMID- 22053345 TI - How to spot a cheetah. PMID- 22053346 TI - Clarifying brain structure, literally. PMID- 22053347 TI - Mapping molecules on the move. PMID- 22053348 TI - A genetic code for phosphoprotein production. PMID- 22053349 TI - HIV in men who have sex with men in the Middle East. PMID- 22053350 TI - Therapeutic drug monitoring in psychiatry. PMID- 22053352 TI - Outcome competences for practitioners in infection prevention and control. PMID- 22053351 TI - AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. AB - Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint eff ort. PMID- 22053354 TI - 'Strategic approach' can reveal benefits. AB - Speaking at last October's Healthcare Estates 2010 conference in Manchester, Peter Haggarty, assistant director, Health Facilities Scotland, outlined some of the key steps and priorities for large healthcare providers seeking to establish and implement an effective asset management strategy, focusing particularly on work ongoing in this area in the Scottish public health service. While any radical change to a large healthcare organisation's existing asset management practices could be "challenging", both for the organisation itself, and for its staff, with "sufficient planning, persistence, and support", such changes could, he told delegates, often result in "unanticipated benefits". HEJ editor Jonathan Baillie reports. PMID- 22053353 TI - (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2. AB - Cyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid and the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamide. Evaluation of a series of COX-2 inhibitors revealed that many weak competitive inhibitors of arachidonic acid oxygenation are potent inhibitors of endocannabinoid oxygenation. (R) enantiomers of ibuprofen, naproxen and flurbiprofen, which are considered to be inactive as COX-2 inhibitors, are potent 'substrate-selective inhibitors' of endocannabinoid oxygenation. Crystal structures of the COX-2-(R) naproxen and COX-2-(R)-flurbiprofen complexes verified this unexpected binding and defined the orientation of the (R) enantiomers relative to (S) enantiomers. (R)-Profens selectively inhibited endocannabinoid oxygenation by lipopolysaccharide-stimulated dorsal root ganglion (DRG) cells. Substrate selective inhibition provides new tools for investigating the role of COX-2 in endocannabinoid oxygenation and a possible explanation for the ability of (R) profens to maintain endocannabinoid tone in models of neuropathic pain. PMID- 22053355 TI - Reducing risk through 'not cutting corners'. AB - A comprehensive introduction to water risk and legislation, with a particular focus on the challenges in healthcare, was provided by Blane Judd, chief executive of the Chartered Institute of Plumbing and Heating Engineering (CIPHE), at a recent IHEEM seminar in London. In the spotlight in the presentation, part of a seminar entitled "Total water management within healthcare premises" were subjects ranging from how to deal with Legionella, and the dangers and potential costs of misconnection, to how to minimise scalding, especially among vulnerable patients, and the infection risks inherent in hydrotherapy pool use. HEJ editor Jonathan Baillie reports. PMID- 22053356 TI - Harnessing science to improve safety. AB - Examining the effectiveness of various wet surface cleaning methods in combating harmful microorganisms in a hospital ward, understanding different healthcare cleaning regimes' impact on reducing slips and trips, evaluating the protection offered by surgical masks against influenza bioaerosols, and independently testing tower crane safety following a number of fatal incidents, are among the broad spectrum of recent projects undertaken by the Buxton-headquartered Health and Safety Laboratory (HSL). As HEJ editor Jonathan Baillie discovered from the organisation's healthcare and patient safety lead, Darren Whitehouse, with around 350 scientists skilled in everything from microbiology to occupational psychology, the range of scientific guidance, expertise, advice, testing, training, and investigation, that the HSL can offer to the healthcare sector is perhaps unrivalled throughout Europe. PMID- 22053357 TI - Third retirement after road well travelled. AB - IHEEM London branch chairman John Crawford retired from full-time employment recently after 49 years, almost to the day, as an electrical engineer, having worked for organisations ranging from a sizeable London regional health authority to London Regional Transport. The Merseyside shipwright's son, who explained that he had "attempted unsuccessfully" to retire twice previously, talked HEJ editor Jonathan Baillie through a varied and interesting career, and gave his views on some of the reasons why the UK engineering profession is currently struggling to secure new blood. PMID- 22053358 TI - Da Vinci facility is state-of-the art. AB - Growing demand for a wide range of surgical procedures, coupled with a strong belief in the advantages--both to surgeons and patients--of minimally invasive robot-assisted surgery, have seen the Royal Wolverhampton Hospitals NHS Trust open a new twin operating theatre suite, equipped with the Midlands' first da Vinci surgical robot, at Wolverhampton's New Cross Hospital. The two theatres, together with accompanying "preparation" and scrub facilities, and a separate five-bed recovery bay to serve several of the hospital's eight other existing main theatres, were completed to time and on budget recently by modular construction specialist, MTX Contracts, under a pound 2 million design and build contract, as HEJ editor Jonathan Baillie reports. PMID- 22053359 TI - Milestone module is a strong proposition. AB - Having only moved into modular building construction early this year, mid-August saw pre-medical installation contractor, Canute International Medical Services (CIMS), complete its first ever such building for the medical sector--a CT scanner unit designed and constructed for the Spire Wellesley Hospital in Southend to "match" an existing MRI facility, and to give the impression to patients of being an integral part of the main hospital building. HEJ editor Jonathan Baillie reports. PMID- 22053360 TI - Calls for concerted barcoding drive. AB - With the NHS in England spending some pound 6 billion annually on hospital supplies, but (says the Department of Health) some English hospitals paying nearly three times as much for the same items as their counterparts, Health Minister, Simon Burns, has called on suppliers to significantly extend use of standardised GS1 barcodes in an attempt to improve "transparency" for procurement staff. The Minister argues that individually barcoding many more hospital-bound items would give procurement teams a clearer, more accurate picture of what they were buying, enable fairer price comparison, and radically improve stock control in many NHS hospitals, potentially reducing NHS procurement costs by millions of pounds. Other anticipated benefits include fewer medication errors, lower risk of wrong-site surgery, and the ability to track and trace everything from surgical instruments to patient beds. HEJ editor Jonathan Baillie reports. PMID- 22053361 TI - From plough to plate--an NHS first? AB - A recent Soil Association survey saw nearly a third of the 1,000 patients questioned about the food they had received during a recent hospital stay report that it was so bad that, at times, they could not recognise what was on their plate (HEJ - September 2011). The resulting report, however, also commended a number of healthcare organisations which had put considerable time, effort, and commitment, into providing first-class patient meals, often at negligible extra cost, and using high quality, locally sourced produce. One NHS Trust pioneering such an approach, while simultaneously boosting the fortunes of local farmers and other food producers, is Sussex Partnership NHS Foundation Trust, which, HEJ editor Jonathan Baillie discovered, is now not only being held up as a national exemplar of good NHS catering practice, but has also recently had the go-ahead for a new pound 2.2 million catering facility. PMID- 22053362 TI - Appeal for legislation on greater safety. AB - An Essex-headquartered company which claims to manufacture the world's leading "brand" of glass vision panel, is calling for legislation to regulate the quality and design of such products. With no statutory governance currently in place, it is concerned that a rash of badly-designed, poorer quality variants, that it says have emerged in recent years, pose a significant self-harm and ligature risk to mentally unwell patients in hospitals, and a potential danger to staff when components like internal fittings and the glass itself, especially should the latter be too thin and thus easy to break, are used as "weapons". HEJ editor Jonathan Baillie reports. PMID- 22053363 TI - Largest healthcare foundations. U.S. foundations awarding health grants, by total award amount, 2009. PMID- 22053364 TI - [Focusing on the retreatment for chronic hepatitis B patients treated with nucleos(t)ide analogue]. PMID- 22053365 TI - [Optimal therapy for chronic hepatitis B patients]. PMID- 22053366 TI - [Retreatment for patients with chronic hepatitis B relapse after initial antiviral therapy]. PMID- 22053367 TI - [Optimal strategy for chronic hepatitis B patients receiving nucleos(t)ide analogue antiviral treatment]. PMID- 22053368 TI - [An introduction of the researches on hepatitis C virus infection from the 46th EASL annual conference]. PMID- 22053369 TI - [Peginterferon alpha combined with ribavirin for the treatment of chronic hepatitis C]. PMID- 22053370 TI - [Down-regulation of hepatitis B virus replication by heparin sulfate-D glucosaminyl-3-O-sulfotransferase 3B1]. AB - OBJECTIVE: To investigate the effect of HS3ST3B1 on hepatitis B virus (HBV) replication. METHODS: HepG2 cells were classified into 7 groups according to the plasmids transfected: (1) Blank group, no plasmid transfected; 2. Positive control, transfected with pCH9-HBV which permits HBV replication; (3) Negative control, transfected with pCH9-HBV + pcDNA3.1 + pTZU6+1; (4) Treatment A, transfected with pCH9-HBV + pCDNA3.1-HS3ST3B1 + pTZU6+1; (5) Interference A, transfected with pCH9-HBV + pCDNA3.1-HS3ST3B1 + psh1126 (a plasmid to interfere HS3ST3B1 expression); (6) Treatment B, transfected with pCH9-HBV + pTZU6+1; (7) Interference B, transfected with pCH9-HBV + psh1126. The levels of HBV DNA were detected in the above groups by Southern blotting. HBV total RNA of Negative control, Treatment A and Interference A were quantified by Real-time PCR to determine the influence of HS3ST3B1 over-expression on the HBV RNA transcription. The activity of the four HBV promoters [core promoter (cp), x promoter(xp), surface antigen promoter1(sp1), surface antigen promoter2 (sp2)] were assayed by Dual-Luciferase Reporter Assay System. The data was analyzed using one way ANOVA, with P < 0.05 indicating statistically meaningful difference. RESULT: Southern blot data revealed the level of HBV DNA in Treatment A and Interference A accounted for 10% +/- 2% and 31% +/- 4% of that in control. Compared with control, a statistical difference existed between Treatment A and Control, with F value equalling to 20.8 and P value equalling to 0.034 respectively. A statistical difference also existed between Interfere A and Treatment A, with F value equalling to 24.9 and P value equalling to 0.021 respectively. The level of HBV DNA in Experiment B was raised by 130% +/- 11% as compared to that in Interference B, and the levels of HBV DNA showed a dose-dependent decrease when H7 cells were transfected with 0.5, 1.0, 1.5 microg pCDNA3.1-HS3ST3B1 respectively. Statistical differences existed between control and H7 transfected with different dose of pCDNA3.1-HS3ST3B1, with F values equalling to 22.7, 20.3, 26.5 and P values equalling to 0.029, 0.041 and 0.015 respectively. Real-time PCR revealed that the HBV total RNA in Treatment A accounted for 17.0% +/- 2.7% of that in control and there was a statistical difference between Treatment A and control, with F value equalling to 25.6 and P value equalling to 0.018. In addition, HBV DNA in Interference A was restored to 74.0% +/- 3.9% of that in control, and there was also a statistical difference between Treatment A and Interference A, with F value equalling to 21.3 and P value equalling to 0.032. However, the down regulation of HBV total RNA had nothing to do with HBV promoters activity. CONCLUSION: HS3ST3B1 can inhibit HBV replication and reduce the level of HBV total RNA, but the downregulation of HBV total RNA may not be the result of direct interaction of HS3ST3B1 and HBV promoters. PMID- 22053371 TI - [Identification the relationship between mutation patterns of rtM204I/V in the polymerase gene and genotypes of hepatitis B virus]. AB - OBJECTIVE: To investigate the relationship between the mutation patterns of rtM204V/I (methionine to valine or isoleucine at position rt204 of reverse transcriptase domain) in hepatitis B virus (HBV) polymerase gene and HBV genotypes. METHODS: A total of 2849 HBV complete genome sequences were retrieved from the GenBank/EMBL/DDBJ. HBV genotypes were determined by using MEGA4 software. The amino acid sequences of the reverse transcriptase (RT) domain were aligned. Data were analyzed using SPSS 13.0. RESULTS Among the 2849 HBV complete genome sequences, 217 strains with Y (I/V) DD were identified. Of them, 120 had YIDD mutation and the genotype/subgenotype distribution was as follows: A (2), B(B2 19), C(C1 1, C2 78, C5 1), D(17), E(1), G(1); 97 had YVDD mutation and the genotype/subgenotype distribution was as follows: A(17), B(B2 22), C(C1 3, C2 48), D(3), G(3), H(1). There is a significant difference in the mutation patterns of Y (I/V) DD among genotypes of A-D, A-C, and between genotype A and B, P < 0.01.There is a difference in the mutation pattern of Y (I/V) DD among genotypes of B-D, between genotype C and D, P < 0.05. Genotype A has a higher tendency to develop YVDD mutation, whereas genotype D has a higher frequency to develop YIDD mutation. The rtM204V-rtL180M mutations were more frequently found in subgenotype B2 than in subgenotype C2 while the rtM204V-rtL180M-rtV173L mutations were more associated with subgenotype C2 (P < 0.01). CONCLUSION: Different HBV genotype/subgenotype may select different mutation pattern in the YMDD domain. Subgenotype C2 is more diversity and complexity than other HBV genotypes/subgenotypes. PMID- 22053372 TI - [Lamivudine-resistant analysis and management for chronic hepatitis B patients with initial lamivudine therapy]. AB - OBJECTIVE: To study the factors influencing the long-term usage of lamivudine (LAM) in chronic hepatitis B (CHB) patients and the management after drug resistance. METHODS: 383 cases of naive CHB patients in our outpatient clinic were treated with lamivudine (100 mg/d) and followed up for at least over 1 year from 2001 to 2010. 129 cases encountered lamivudine-resistance and were then divided into two groups: patients in group A were switched to adefovir dipivoxil (ADV) alternative treatment and those patients in group B were added with ADV for continuous treatment. Efficacy assessment factors included serum HBV markers, HBV DNA, ALT, AFP and other biochemical indicators. RESULTS: Among the 383 cases, patients with HBV DNA negative conversion (PCR below test line) at 3 months, 6 months, 1 year, 2 years, 3 years and > 3 years after initial treatment were respectively 156 cases (40.7%), 213 cases (55.6%), 228 cases (59.5% ), 217cases (56.7%), 214 cases (55.9%) and 213 cases (55.6%). HBeAg/HBeAb seroconversion occurred in 62 cases (22.6%). 12 cases were found with primary LAM resistance, 129 cases with HBV breakthrough and rebound, the cumulative resistance rate was 36.8% and the cumulative rebound rate was 34.8%. High baseline viral load, baseline ALT levels < 2 ULN, Lower virologic response rate at week 24 were associated with a higher rebound rate (chi2 is 35.716, 8.728, 43.534, respectively, all with P < 0.01).Viral breakthrough and rebound occurred in 112 patients (86.8%) within 1 year and a half, 123 patients (95.3%) occurred at the end of 2 years and no patient with viral breakthrough and rebound after 5 years. For the patients with viral rebound in group A and group B, the rates of HBV DNA loss were 22.7% (15/66) and 58.7% (37/63) respectively, and the viral response rates were 59.1% (39/66) and 87.3% (52/63) respectively, with chi2 values equaled 17.364 and 12.975 respectively (P < 0.01). CONCLUSION: For the chronic hepatitis B patients on initial treatment with lamivudine, the viral rebound occurred mainly within 2 years. LAM combined with ADV is more effective than ADV alone for lamivudine-resistant patients. PMID- 22053373 TI - [Liver histological changes in chronic hepatitis B patients with elevated ALT less than 2 x ULN]. AB - OBJECTIVE: To investigate the relevant factors of liver histological changes in chronic hepatitis B (CHB) patients with mildly elevated ALT and to explore the clinical values of these factors on anti-viral treatment. METHODS: A total of 152 CHB patients with mildly elevated ALT (less than 2 x ULN) who underwent liver biopsy were included in the study. Correlations between routine laboratory markers, liver histological inflammation grade and fibrosis stage were statistically assessed by Spearman correlation analysis, one-way ANOVA, area under the curve (AUC) of the receiver operating characteristic curves (ROC) and Logistic regression statistical analysis. RESULTS: All patients in the study showed various hepatic histological damages. Among the 152 patients 50 (32.9%) were found with inflammation grade 1 (G1), 42 (27.6%) with G2, 46 (30.3%) with G3 and 14 (9.2%) with G4. 16 patients (10.5%) were found with fibrosis stage 2 (S2), 25 (16.5%) with S3 and 41 (27.0%) with S4. Routine laboratory markers Alb, BPC and WBC were significantly correlated with hepatic histological inflammation grade and fibrosis stage. Marked liver fibrosis and moderate to severe liver damage were significantly higher in patients aged more than 40 years as compared to those less than 40 years of age (P = 0.002, P = 0.010). The regression equation P = 1/[1+e-(9.36250-1625Alb-0.0234BPC)] was established with sensitivity and specificity of 83.3% and 65.0%, respectively. CONCLUSION: 67.8% of CHB patients with mildly elevated ALT have significant injury to the liver tissue. CHB patients aged more than 40 years have a significant increase of marked liver fibrosis and moderate to severe liver damage. The regression equation is valuable to predict whether CHB patients need antiviral therapy or not. PMID- 22053374 TI - [Comparison study of HBV-P mutation detection by MALDI-TOF Ms and direct PCR sequencing]. AB - OBJECTIVE: To compare the sensitivities of MALDI-TOF MS and direct PCR sequencing on gene mutations detection of hepatitis B virus. METHODS: 100 serum samples from chronic hepatitis B patients were collected, which consisted of 90 serum samples (study group) from 90 chronic hepatitis B patients received nucleoside analogues (NA) therapy for more than 1 year and HBV DNA titer still higher than 500 copies/ml and 10 serum samples (blank group) from 10 chronic hepatitis B patients never treated with antiviral therapy and HBV-DNA titer higher than 1 x 10(5) copies/ml. 9 known mutations associated with HBV P gene in these samples were detected by MALDI-TOF MS and direct PCR sequencing at the same time, TYPE4.0 software and Sequence Navigator software were used to analyze the results separately. RESULTS: (1) In study group, mutations were detected in 53 samples and the total mutation sites were 86 by MALDI-TOF MS with a positive detection rate of 58.89%, whereas only 19 samples were found with mutations and totally 28 mutation sites were detected by direct PCR sequencing, the positive detection rate was 21.11%. The positive detection rate by MALDI-TOF MS was higher than that by direct PCR sequencing and the difference was statistically significant (P < 0.05). In blank group, no mutations were detected by any method. (2) In study group, when the HBV DNA titers were at 500-1000 copies/ml, 10(3)-10(4) copies/ml and 10(4)-10(5) copies/ml, the positive mutation detection rates by MALDI-TOF MS were 50%, 52.08% and 77.27% respectively, higher than that by direct PCR sequencing, which were only 0%, 8.33% and 45.45%. The difference was still statistically significant (P < 0.05). CONCLUSIONS: MALDI-TOF MS had higher detection sensitivity for known mutation sites as compared to direct PCR sequencing method. PMID- 22053375 TI - [The influence of HBV and its antigens on the expressions of JAK-STAT signal transduction pathway molecules and antiviral proteins of IFN alpha]. AB - OBJECTIVE: To investigate the possible influence of HBV and its antigens on the expressions of JAK-STAT signal transduction pathway molecules and the antiviral proteins of IFN alpha. METHODS: The HepG2 cells were transfected with pSM2, pHBS2 S and pHBc-EGFP plasmids which express HBV whole particles or S-antigen, Pre-S antigen and core antigens. The infectious supernatant from HepG2.2.15 cells and the pured HBV proteins which contained the S, Pre-S antigens were used to treat the HepG2 cells. Northern blot and RT-PCR were applied to analyse the expressions of the antiviral proteins MxA, 2' -5' OAS, 9-27 and the JAK-STAT signal transduction pathway molecules STAT1 in HepG2 cells responded to the IFN alpha treatment. RESULTS: The HepG2 cells transfected with pSM2, pHBS2-S and pHBc-EGFP plasmids could express whole HBV particles and HBsAg, Pre-S antigen and HBcAg. The quantitation of expressed HBV particles and antigens increased significantly during the course of transfection. Northern blot hybridization analysis indicated that the HepG2 cells expressed IFN alpha antiviral proteins MxA, 2' -5' OAS and 9 27. When transfected with pHBV-dimer, pHBS2-S, pHBc-EGFP plasmids, the IFN/A antiviral proteins MxA, 2' -5' OAS and 9-27 in transfected cells were reduced greatly as compared to the un-transfected HepG2 cells, and the expressed antiviral proteins decreased sharply with the development of transfection time. Furthermore, the expression of IFN alpha JAK-STAT signal transduction pathway molecule STAT1 was also inhibited with the expression of HBV particles and HBV antigens in transfected HepG2 cells. CONCLUSIONS: The HBV and its antigens influence the expressions of IFN alpha JAK-STAT signal transduction pathway molecules and antiviral proteins in the hepatocellular models in vitro. It is indicated that HBV might possess the activity to antagonise or counteract the IFN alpha antiviral action. PMID- 22053376 TI - [Safety evaluation and quality control of MSCs from hepatitis B patient in vitro]. AB - OBJECTIVE: To get mesenchymal stem cells (MSCs) from hepatitis B patient and to valuate the safety and quality after long-term culture in vitro. METHODS: The cells obtained directly from bone marrow and cultured in Mesen Pro medium supplemented with FGF, and the morphology of MSCs was observed. Surface antigens of the MSCs were analyzed by flow-cytometry. The bacteria, virus, endotoxin and residual serum of cell suspension were detected. The MSCs and perpheral blood T lymphocytes were co-cultured in 48 well plates for 72 h and the T lymphocyte proliferation was measured by using MTT reduction method and the effect of MSCs on T lymphocyte transformation stimulated by PHA was also observed. The oncogenicity of MSCs was verified by the tumorigenesis test in sofo agar. The genetic stability of MSCs was examined by karyotype analysis. RESULT: The MSCs from hepatitis B patient could be passaged to many generations and had strong abilities of proliferation. They expressed stem cell-surface antigens and maintained normal karyotype, prevented the pollution of bacteria and viruses, inhibited the immune response of allogenic T lymphocytes and no oncogenicity found. CONCLUSION: The MSCs have proliferative potentials, can be passaged in long-term cultures in Mesen Pro medium without oncogenicity, can maintain normal karyotype, can inhibit the immune response of T lymphocytes and can alleviate the grafe-versus diseases. The MSCs can be served as a new type of cells in cell and gene therapy. PMID- 22053377 TI - [Study on type I interferon and phospho-IRF3 in murine liver dendritic cells after intervened by HBV]. AB - OBJECTIVE: To detect the secretions of type I interferon and the expressions of phospho-IRF3 in murine liver dendritic cells intervened by HBV. METHODS: The murine liver dendritic cells were isolated via anti-CD11c microbeads and were incubated in the presence of GM-CSF and IL-4 to induce the DC generation and proliferation in 24-well cell culture plates. HBV virions were isolated via ultracentrifugation and were detected by quantitative Realtime-PCR. The DCs were divided into two groups: one group was cultured with HBV virions for 24 hours, the other group was cultured without HBV as control group. The cells were harvested at Oh, 1h, 2h, 6h and 24h after being stimulated with poly I:C and the expressions of p-IRF3 and the concentration of IFN beta in supernatants were detected with western blot and ELISA respectively. RESULTS: The IFN beta concentrations at 0 h, 6 h and 24 h in the supernatants of the HBV group and the control group were (12.38 +/- 3.71) pg/ml, (88.67 +/- 9.01) pg/ml and (69.89 +/- 5.80) pg/ml vs (10.83 +/- 4.11) pg/ml, (137.68 +/- 12.28) pg/ml and (72.25 +/- 8.61) pg/ml, respectively. No statistical differences found at 0 h (t = 0.8398, P > 0.05) and 24 h (t = 0.6820, P > 0.05) between the two groups except that at 6 h (t = 9.653, P < 0.01). The expressions of phospho-IRF3 in HBV group were lower than that in control group. CONCLUSIONS: The type I interferon secretion and the phospho-IRF3 expression were decreased in murine liver dendritic cells when intervened by HBV. PMID- 22053379 TI - [The construction of IGF-II P4 promoter-driven tk expression vector]. AB - OBJECTIVE: To investigate the selective killing effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) suicide gene system controlled by human IGF-II P4 promoter on HCC cells in vitro. METHODS: Recombinant shuttle plasmid vectors driven by IGF-II P4 promoter and driven by CMV promoter were constructed by techniques of gene recombination. The recombinant shuttle plasmids were then transfected into HepG2 and HeLa cells by techniques of lipidosome transfection. EGFP expression was detected by fluoroscopy. Tk and EGFP mRNA expression were detected by RT-PCR. The selective killing effect after GCV application was determined with MTT method. Statistical analysis was performed with ANOVA analysis. RESULTS: Identification of pDC316-tkEGFP-P4 by enzyme digestion and sequencing analysis showed that the construction of the recombinant shuttle plasmid was correct. It was found that green fluorescence protein could only be seen in HepG2 cells, not in HeLa cells. The results of RT-PCR showed only two bands could be seen in the samples of pDC316-tkEGFP-P4 transfected HepG2 cells. The growth of HepG2 cells transfected with pDC316-tkEGFP-CMV and pDC316-tkEGFP-P4 were inhibited remarkably, the growth inhibition rates were 6.95% +/- 0.67%, 24.99% +/- 1.53%, 49.68% +/- 1.68%, 71.85% +/- 3.28% and 4.83% +/- 0.35% vs 17.34% +/- 1.15%, 30.17% +/- 1.30%, 40.39% +/- 0.82% (F = 24.055, P < 0.05), respectively. The growth of HeLa cells transfected with pDC316-tkEGFP-CMV were also inhibited, the growth inhibition rates were 6.36% +/- 0.83%, 23.95% +/- 1.72%, 45.13% +/- 1.64% and 69.38% +/- 3.17%, respectively. The growth of HeLa cells transfected with pDC316-tkEGFP-P4 was not inhibited. The growth inhibition rates were 0.91 +/- 0.04, 1.18 +/- 1.32, 1.19 +/- 0.10 and 1.32 +/- 0.05 (F = 26.469, P < 0.01) , respectively. CONCLUSION: The shuttle plasmid vector carrying the tkEGFP fusion protein gene driven by IGF-II P4 promoter has been constructed successfully and its specific expression in HepG2 cells provided the basis for targeted gene therapy for HCC. PMID- 22053378 TI - [The effects of curcumin derivative on experimental steatohepatitis]. AB - OBJECTIVE: To observe the effects of curcumin derivative on non-alcoholic steatohepatitis (NASH). METHODS: 60 SD male rats were randomly divided into 5 groups. The NASH model was induced by high fat diet combined with carbon tetrachloride. These rats were then treated with curcumin and curcumin derivative, saline treating group as control. The serum biochemical parameters and liver histological examinations were observed. The TNF alpha, NF-kappa B and HMG-CoA reductase mRNA transcriptions of liver tissue were detected with RT-PCR. The protein expressions of TNF alpha and NF-kappa B were detected by western blot. RESULTS: Compared with the saline group, A remarkable reduction was observed in serum ALT (U/L), AST (U/L) and TC (mmol/L) in rats treated with curcumin derivatives [(69.20 +/- 27.58) vs (102.43 +/- 47.29), (158.00 +/- 39.15) vs (229.50 +/- 105.20) and (2.08 +/- 0.30) vs (2.58 +/- 1.02), P < 0.05]. The degrees of fibrosis were significantly alleviated; Compared with curcumin group, liver index and serum ALT, AST of curcumin derivative group were also significantly decreased [(4.88 +/- 0.62) vs (5.16 +/- 0.61); (69.20 +/- 27.58) vs (82.5 +/- 33.23); (158.00 +/- 39.15) vs (211.75 +/- 106.30), P < 0.05]; The liver steatosis and inflammation grade were also significantly improved .The gene transcriptions of TNF alpha, NF-kappa B and HMG-CoA reductase in curcumin derivative group were significantly lower than those in curcumin and saline group (P < 0.05). CONCLUSION: These results indicate that the water-soluble curcumin derivative displays superior bioavailability to the parent curcumin, which can effectively improve the lipid metabolism and delay the progression of hepatic fibrosis in rats with steatohepatitis. PMID- 22053380 TI - [Effect of microbial pharmaceutics on the function of NKT cells in rats with non alcoholic steatohepatitis]. PMID- 22053381 TI - [Abnormality of NF- kappa B expression and the clinical implications in patients with HBV-related hepatocellular carcinoma]. PMID- 22053382 TI - [The value of MELD in the assessment of short-term prognosis of severe hepatitis by artificial liver treatment]. PMID- 22053383 TI - [Efficacy comparison between bicyclol and polyene phosphatidylcholine treatments for alcoholic liver disease]. PMID- 22053384 TI - [Effects of ischemic precondition on the content of cholesterol in mitochondria and cytochrome c expression in hepatocytes following cold preservation in rats]. PMID- 22053385 TI - [HBV resistance mutants before and after adefovir dipivoxil treatment and the relationship with HBV genotypes]. PMID- 22053386 TI - [Antiviral therapy of HCV infection in patients with uraemia on maintenance of hemodialysis and waiting for renal transplantation: a case report]. PMID- 22053387 TI - [Research advances on hepatitis B virus covalently closed circular DNA]. PMID- 22053388 TI - Largest group practices. Ranked by number of full-time-equivalent physicians, based on MGMA data as of September 2011. PMID- 22053389 TI - Hospitals with highest readmission rate. Ranked by 30-day risk-adjusted readmission rate, based on the Hospital Compare database. PMID- 22053390 TI - [Theory of the onset of initial contraction of tuberculosis]. PMID- 22053391 TI - Consensus statement on decision making in junctional trauma care. AB - Improvised explosive devices (IEDs) cause 60% of all UK fatalities in the current campaign in Afghanistan. Shorter evacuation timelines now deliver patients at the edge of the physiological envelope of survivability meaning that the available time period for haemorrhage control and initial wound surgery is short--often no more than 75 minutes. The concepts and practise of 'right turn resuscitation', damage control general and orthopaedic surgery, on-table 'ITU' pause/catch-up and then further resuscitative surgery are commonplace. In Helmand in 2011, multiple team operating is now the norm on these casualties with up to seven surgeons and three anaesthetists simultaneously involved in the operative care of one patient. This usually involves one consultant orthopaedic surgeon and trainee per lower limb, a plastic surgeon on the upper limb or faceleyes and two general surgeons obtaining proximal vascular control or in-cavity haemorrhage control. A combined meeting in 2010 of the Lower Limb and Torso Trauma Working Groups of the Academic Department of Military Surgery and Trauma produced 25 clear, didactic statements to provide advice to the consultant team. The fundamental message is that bleeding is always a surgical problem. Some adjuncts are available; pressure (direct and indirect), compressive bandaging, haemostatic dressings and tourniquets. However, only formal surgical control, by whatever means is definitive. Early proximal control is mandatory: in all cases, rapidly obtain the most distally appropriate proximal control above the zone of injury. PMID- 22053392 TI - Inter-war Bucharest: city in a garden. PMID- 22053393 TI - Kosovo and the refugee crisis, 1999: the search for patterns amidst the prejudice. PMID- 22053394 TI - Longing for Paris: the Europeanized dream of Caracas urbanism, 1870-1940. PMID- 22053395 TI - [Recent tendencies in researching Latin American social and ethnic groups of the 19th and 20th centuries]. PMID- 22053396 TI - Residents' reactions to post-war slum clearance in England. PMID- 22053397 TI - Robert Schmidt and the public park policy in the Ruhr district, 1900-1930. PMID- 22053398 TI - The development of residential urban renewal policies in England: planning for modernization in the 1960s. PMID- 22053399 TI - The domestication of violence: forging a collective memory of the Holocaust in Britain, 1945-6. PMID- 22053400 TI - The image of the Gypsy in German Christendom. PMID- 22053401 TI - The queer Jew: gender, sexuality and Jean-Paul Sartre's anti-Antisemitism. PMID- 22053402 TI - The reconstruction of Upper Normandy: a tale of two cities. PMID- 22053403 TI - The redevelopment of Rotterdam since 1945. PMID- 22053404 TI - [Overlooked victims: Korean survivors of the atomic bombs]. PMID- 22053405 TI - Changing food production and quality of diet in India, 1947-98. PMID- 22053406 TI - Corn and crisis: Malthus on the high price of provisions. PMID- 22053407 TI - Malthusian models and Chinese realities: the Chinese demographic system, 1700 2000. PMID- 22053408 TI - Marital and fertility careers of Russian women born between 1910 and 1934. PMID- 22053409 TI - Separating analysis from politics: acid rain in Europe. PMID- 22053410 TI - Smallpox in nineteenth-century India. PMID- 22053411 TI - The Bangladesh fertility decline: an interpretation. PMID- 22053412 TI - The delayed western fertility decline: an examination of English-speaking countries. PMID- 22053413 TI - The global and regional impact of mortality and fertility transitions, 1950-2000. PMID- 22053414 TI - The planning of Reykjavik, Iceland: three ideological waves - a historical overview. PMID- 22053415 TI - Vice into virtue? Progressive politics and welfare reform in continental Europe. PMID- 22053416 TI - Eleanor Rathbone on the Remuneration of Women's Services. PMID- 22053417 TI - A return to the imaginary: psychoanalysis and travel in Vernon Lee's travel essays. PMID- 22053418 TI - A royal bride for two brothers: Marie-Francoise of the Savoy-Nemours and the French lobby at the court of Portugal, 1666-1672. PMID- 22053419 TI - Childhood in the promised land: working-class movements and pedagogical reform in the "colonies de vacances" in France, 1880-1960. PMID- 22053420 TI - Churchyard and civic square: the production of public spaces in late medieval and early modern Lyon. PMID- 22053421 TI - Classless monster: the representation of criminals in Parisian news, 1830-1900. PMID- 22053422 TI - Defending the honor of French surgery, 1760-1788. PMID- 22053423 TI - From "petite patrie" to national "solidarite": regionalism and inter-class alliances in mutual aid societies. PMID- 22053424 TI - [Protestant cemeteries in Provence, 17th-19th centuries]. PMID- 22053425 TI - National preferences and colonial cuisine: seeking the familiar in French Vietnam. PMID- 22053426 TI - Paris-lesbos: lesbian social space in the modern city, 1870-1940. PMID- 22053427 TI - Reform: Stay calm amid the storm. PMID- 22053428 TI - Finance: Physician, heal thy costs. PMID- 22053429 TI - Reconfiguration: The 500 m pounds question. PMID- 22053430 TI - Public health: Doctor Carrot won't see you now. PMID- 22053431 TI - Innovation, now. PMID- 22053432 TI - Patient involvement: Power of good. PMID- 22053433 TI - Finance: Is it time to get personal? PMID- 22053434 TI - Strategic care for complex needs: hand in hand. PMID- 22053436 TI - [SCIT helps with animal fur allergy: allergens on 4 legs]. PMID- 22053435 TI - [What can be expected with mammography: surprising new "space occupying lesions" in the breast. Mastalgia, hyaluronic acid]. PMID- 22053437 TI - [Therapy possibilities and therapy chances: "cat sensitive patients should receive specialist immunotherapy" (interview by Robert Bublak)]. PMID- 22053438 TI - [What is good for the heart pump also helps in impotence: good sex: an affair of the heart]. PMID- 22053439 TI - [Low thrombocyte count: when does it become dangerous?]. PMID- 22053440 TI - [Naturopathy consultation. Dysmenorrhea]. PMID- 22053442 TI - [MRSA is spreading among diabetic patients: chronic wounds: El Dorado for problem pathogens]. PMID- 22053441 TI - [Vegetative state patient Rom Houben: certainly did not wake up]. PMID- 22053443 TI - [Surprising thoracic x-ray finding: effusion, plaque or tumor?]. PMID- 22053444 TI - [Are you obliged to report a bullet wound?]. PMID- 22053445 TI - [Medical confidentiality]. PMID- 22053446 TI - [The obligation to report child abuse]. PMID- 22053447 TI - [Emergency checklist: nose bleeding]. PMID- 22053448 TI - [Differential diagnosis and therapeutic options in acute sore throat]. PMID- 22053449 TI - [Conservative therapy of low backpain: what really helps]. PMID- 22053450 TI - Examples of energy self-sufficient municipal nutrient removal plants. AB - In Austria, two municipal WWTPs (the Strass TP and Wolfgangsee-Ischl TP) operated with nutrient removal and aerobic sludge digestion are now energy self sufficient. This is the result of a longstanding and on-going optimisation process at both plants including optimal aeration control and control of the aerobic section of the aeration tank to optimise denitrification and prevent degradation of particulate organic matter that should be degraded in the digester. Both TPs are now equipped with energy-efficient CHP units. However, it is maybe more sustainable to use the biogas as biomethane/bio-fuel than in conventional CHP at the WWTP. It is shown that energy self-sufficiency should be in reach at other municipal WWTPs, too. PMID- 22053451 TI - Effect of bacterial growth stage on resistance to chlorine disinfection. AB - The mechanisms and factors that affect microbial resistance to chlorine disinfection have not been fully elucidated. In this study, we investigated the impact of the cell growth stage on chlorine disinfection efficiency. Specifically, we evaluated the impact of the growth stage on chlorination resistance by comparing the inactivation efficiencies of two indicator bacterial strains (Escherichia coli K12 and Escherichia coli O157:H7) obtained from various growth phases, using Chick-Watson kinetic parameters. For both E. coli strains (K12 and O157:H7), the inactivation rate constants are the lowest at stationary phase (0.19 and 0.32) compared to those at initial lag (0.54 and 0.76) and exponential growth phase (0.63 and 0.69), respectively. These results suggested that the abundance of resistant subpopulations increases at stressed stationary conditions and E. coli cells obtained from the stationary growth phase exhibited more resistance and lower inactivation efficiency compared to those from the lag and exponential phases. This implies that microbes in wastewater treatment process with varying solids retention times (SRTs, which indicate growth rates) may show different extents of chlorine resistance. Comparison of the coefficient of dilution (n) values in both E. coli strains for the various growth phases suggest that cells seem to be more sensitive to disinfectant concentration at the stationary-lag phase than that at the exponential stage. Comparing the two E. coli strains, higher inactivation rates were observed for the pathogenic O157:H7 than for K12 at different stages of growth. The strain-to-strain variability in survivability to chlorine exposure has to be considered when selecting indicator microorganisms for water quality monitoring. PMID- 22053452 TI - Numerical modelling: a tool for better constructed wetland design? AB - There is a need for a simplified computer-based design tool for subsurface flow constructed wetlands (CWs) which is based on process-based numerical models. Parameters of existing design guidelines and rules have been derived from experiments under specific conditions. Therefore designing CWs using these parameters is limited to these conditions (i.e., temperature, wastewater composition, filter material, etc.). Process-based numerical models describe the main processes in CWs in detail. If the design of CWs is based on these models it will be possible to design CWs for a variety of different boundary conditions and therefore the main limitation of existing design guidelines and rules could be overcome. The use of process-based models is currently limited mainly due to their complexity in structure and use. To make numerical modelling a useful and applicable tool for design, a simplified computer-based design tool that does not require special knowledge of numerical modelling is needed. Additionally, simple models for pre- and post-treatments are also required. Besides allowing designs for various boundary conditions, design tools based on process-based models can also predict the dynamic behaviour of the designed system thus showing e.g., the higher robustness of CWs against fluctuating inflows and peak loads compared to other treatment solutions. Such a tool could increase the quality of CW design and the acceptance and use of CW simulation in practice. PMID- 22053453 TI - Performance of a constructed wetland for treating farm-yard dirty water. AB - Constructed wetlands (CWs) have been used to treat agricultural effluents with varying success especially with respect to their operational efficiency in winter and ability to retain phosphorus. Dirty water (DW) from dairy farms is a mixture of manure contaminated runoff and milk parlour washings with a highly polluting biochemical oxygen demand (BOD) < or =3000 mg/L. The initial performance a CW of a 1.2 ha horizontal flow CW consisting of five ponds in series designed to treat DW from a dairy unit was assessed over four years. Ponds were earth-lined and shallow (0.3 m) with a water residence time of 100 days and planted with five species of emergent macrophytes. In comparison to CW inflow, annual reductions were as follows: BOD 99%, P 95% and N 92.8%. Coliforms were reduced by a 10(-5) factor to natural levels. From May to October there was little CW discharge due to evaporative losses. Final effluent quality was poorest in February but remained within a regulatory effluent standard for BOD of 40 mg/L. If the CW had only four ponds (25% less surface area) effluent would have failed the BOD standard in three years. PMID- 22053454 TI - Towards a complete recycling of phosphorus in wastewater treatment--options in Germany. AB - Global reserves of mineral phosphorus are finite and the recycling of phosphorus from wastewater, a significant sink for phosphorus, can contribute to a more sustainable use. In Germany, Switzerland, and the Netherlands, an increasing percentage of municipal sewage sludge is incinerated and the contained phosphorus is lost. This paper reviews current technologies and shows that a complete phosphorus recovery from wastewater is technically feasible. Depending on the composition of the sewage sludge ash (SSA), there are various options for phosphorus recovery that are presented. Iron-poor SSAs can be used directly as substitute for phosphate rock in the electrothermal phosphorus process. SSAs with low heavy metal contents can be used as fertilizer without prior metal elimination. Ashes not suitable for direct recycling can be processed by thermal processes. Operators of wastewater treatment plants can additionally influence the ash composition via the selection of precipitants and the control of (indirect) dischargers. This way, they can choose the most suitable phosphorus recovery option. For sewage sludge that is co-incinerated in power plants, municipal waste incinerators or cement kilns phosphorus recovery is not possible. The phosphorus is lost forever. PMID- 22053455 TI - Understanding urban residential end uses of water. AB - The 'end use' of water is a breakdown of the total household water usage such as water used for toilets, showers, washing machines, taps, lawn watering, etc. Understanding end uses of water will enable water planners, water authorities and household owners determine where water is used/wasted, how much and how often. This paper describes the end uses of water from a number of single-family homes in Greater Melbourne, Australia. The study involves the analysis of water consumption data recorded at 5-s intervals from logged households collected by Yarra Valley Water in Melbourne in 2004. The study determines how much water is used for outdoor and indoor purposes in a single-family home in Melbourne and compares the water usage during winter and summer. Hourly patterns of major end uses of water are also developed. The aim of this study is to improve the understanding of the end uses of water and to assist where to focus water conservation efforts that would be most effective financially and environmentally, and be acceptable to everyone. PMID- 22053456 TI - An assessment of the checkpoint bioassay concept for full scale wastewater UV reactor validation. AB - In an effort to help policy makers and manufacturers understand the impact of parameter uncertainties on UV reactor performance, a numerical bioassay model was developed by integrating a UV reactor model based on computational fluid dynamics with a Monte Carlo model developed to account for parameter uncertainty. For the model implemented, it was determined that reactor performance uncertainty was less than 6%. The integrated model was used to evaluate several checkpoint bioassay criteria including one currently used by the California Department of Public Health. The model showed that these criteria failed to take into account the fact that in an ideal case, a full scale reactor will pass a single checkpoint test 50% of the time. In reality, differences in equipment measurement errors between the system validation and checkpoint bioassay, and limitations of the power law form of the dose monitoring equation in accurately representing system validation data will result in poorer than expected performance. It was suggested that such checkpoint criteria be modified by crediting the inherent over-sizing of full scale reactors. PMID- 22053457 TI - Submersible microbial fuel cell for electricity production from sewage sludge. AB - A submersible microbial fuel cell (SMFC) was utilized to treat sewage sludge and simultaneously generate electricity. Stable power generation (145 +/- 5 mW/m2, 470 omega) was produced continuously from raw sewage sludge for 5.5 days. The maximum power density reached 190 +/- 5 mW/m2. The corresponding total chemical oxygen demand (TCOD) removal efficiency was 78.1 +/- 0.2% with initial TCOD of 49.7 g/L. The power generation of SMFC was depended on the sludge concentration, while dilution of the raw sludge resulted in higher power density. The maximum power density was saturated at sludge concentration of 17 g-TCOD/L, where 290 mw/m2 was achieved. When effluents from an anaerobic digester that was fed with raw sludge were used as substrate in the SMFC, a maximum power density of 318 mW/m2, and a final TCOD removal of 71.9 +/- 0.2% were achieved. These results have practical implications for development of an effective system to treat sewage sludge and simultaneously recover energy. PMID- 22053458 TI - Investigation of the efficiency of a tubular continuous-flow photoreactor with supported titanium dioxide nanoparticles in the removal of 4-nitrophenol: operational parameters, kinetics analysis and mineralization studies. AB - In this study, to investigate the application of heterogeneous photocatalysis in the removal of organic contaminants from aqueous media a novel tubular continuous flow photoreactor with supported TiO2-P25 on glass plates was designed and constructed. The photoreactor comprises six quartz tubes and a UV lamp which was placed in the center of the quartz tubes. 4-nitrophenol (4-NP) as a most refractory pollutant was chosen as a probe pollutant to examine the photoreactor efficiency for environmental cleaning applications. Results of experiments show that the removal efficiency of 4-NP in this photoreactor is a function of photoreactor length, gas and liquid flow rates and 4-NP initial concentration. Kinetics analysis indicates that degradation of 4-NP in continuous-mode can be modeled with the Langmuir-Hinshelwood (L-H) model (k(L-H) = 1.5 mg L(-1) min(-1), K(ads) = 0.11 mg(-1) L). A design equation was obtained with a combination of L-H modified equation and tubular reactor design equation. This equation can be used for estimation of 4-NP concentration in different photoreactor lengths under various operational parameters. Mineralization study was followed through total organic carbon (TOC) analysis and measurement of nitrite and nitrate as final degradation products. PMID- 22053459 TI - Advanced electro-Fenton degradation of biologically-treated coking wastewater using anthraquinone cathode and Fe-Y catalyst. AB - The electrocatalytic activity of bare and 2-ethyl anthraquinone-modified graphite felt (2-EAQ/GF) toward oxygen reduction was investigated using a cyclic voltammetry technique in a neutral solution. The prepared cathodes were tested for electrogeneration of H2O2 and electro-Fenton oxidation (EFO) treatment of neutral coking wastewater (CW) after biological process, using a graphite anode and Fezeolite Y catalyst. The results showed that (i) H2O2 yield and current efficiency greatly depended on cathodic potential and materials; (ii) hydroxyl radicals, generated from Fe-zeolite Y-catalyzed H2O2 decomposition, played a great role in EFO treatment, while anodic direct and indirect oxidation was insignificant; (iii) chemical oxygen demand, total organic carbon (TOC) and acute toxicity of wastewater decreased by 40-50, 30-40 and 50-60%, respectively, and biodegradability increased after 1 h of EFO treatment. Due to the free-pH adjustment, EFO presents a potential engineering application for advanced treatment of CW. PMID- 22053460 TI - Temperature effects on the trophic stages of perennial rye grass anaerobic digestion. AB - Continuous Stirred Tank Reactors (CSTRs), operated in batch mode, were used to evaluate the feasibility of psychrophilic (low temperature) digestion of perennial rye grass in a long term experiment (150 days) for the first time. The reactors were operated in parallel at 3 different temperatures, 10, 15 and 37 degrees C. Hydrolysis, acidification and methanogenesis were assessed by VS degradation, by soluble chemical oxygen demand (SCOD) and volatile fatty acids (VFA) production, and by methane production, respectively. Hydrolysis was the rate-limiting step at all temperatures and the rates and extent of hydrolysis were considerably lower at 15 and 10 degrees C, than at 37 degrees C. The total VS degradation was 53%, 34% and 19% at 37, 15 and 10 degrees C, respectively. Acidification was not affected by temperature and VFA production and consumption was balanced in all cases, except at 10 degrees C. Methane yields were 0.215 m3 CH4 kg(-1) VS(-1) added, 0.160 m3 CH4 kg(-1) VS(-1) added and 0.125 m3 CH4 kg(-1) VS(-1) added at 37, 15 and 10 degrees C, respectively. Methanogenesis was not strongly affected at 15 C but it became rate-limiting at 10 degrees C. Overall, the solid degradation and methane production performance under psychrophilic conditions was encouraging and greater than previously reported. Considering the non-acclimated, mesophilic nature of the inoculum, there are grounds to believe that low-temperature anaerobic digestion of grass could be feasible if coupled to efficient hydrolysis of the biomass. PMID- 22053461 TI - RO brine treatment and recovery by biological activated carbon and capacitive deionization process. AB - The generation of brine solutions from dense membrane (reverse osmosis, RO or nanofiltration, NF) water reclamation systems has been increasing worldwide, and the lack of cost effective disposal options is becoming a critical water resources management issue. In Singapore, NEWater is the product of a multiple barrier water reclamation process from secondary treated domestic effluent using MF/UF-RO and UV technologies. The RO brine (concentrates) accounts for more than 20% of the total flow treated. To increase the water recovery and treat the RO brine, a CDI based process with BAC as pretreatment was tested. The results show that ion concentrations in CDI product were low except SiO2 when compared with RO feed water. CDI product was passed through a RO and the RO permeate was of better quality including low SiO2 as compared to NEWater quality. It could be beneficial to use a dedicated RO operated at optimum conditions with better performance to recover the water. BAC was able to achieve 15-27% TOC removal of RO brine. CDI had been tested at a water recovery ranging from 71.6 to 92.3%. CDI based RO brine treatment could improve overall water recovery of NEWater production over 90%. It was found that calcium phosphate scaling and organic fouling was the major cause of CDI pressure increase. Ozone disinfection and sodium bisulfite dosing were able to reduce CDI fouling rate. For sustainable operation of CDI organic fouling control and effective organic fouling cleaning should be further studied. PMID- 22053462 TI - Decision-making criteria and indicators for water and sanitation projects in developing countries. AB - Water and sanitation projects for solving the needs of small communities in developing countries are complex in nature and involve complex decision-making, which must consider technical, socioeconomic and environmental dimensions. Multicriteria analysis (MCA) is a suitable decision-aid method that scores a finite number of options on the basis of a set of evaluation criteria. The main challenge in MCA is choosing the appropriate criteria and evaluation indicators to use for assessment. The aim of this paper is to present a comprehensive and wide list of criteria and evaluation indicators as a guideline in MCA of water and basic sanitation projects in small rural communities of developing countries. First, the paper details the general criteria to be considered in all the projects, which are classified in to 4 main groups: technical (e.g., local resources use, appropriate management); social (e.g., local community participation, overcoming discrimination of conflict); economic (e.g., low cost, employment of local staff) and environmental criteria (e.g., atmospheric emissions, water pollution). Then, it describes technical criteria to be additionally considered in each specific type of project: water supply (e.g., water needs, independent access), water treatment (e.g., constant resource availability, flexibility of use for different types of water) and basic sanitation projects (e.g., maximum number of people per system, effluent quality). PMID- 22053463 TI - Research of the performance of pulse electrohydrodynamics in blockage removal. AB - In line with contemporary trends and seeking to develop new methods and technologies, a new, original technology was explored and designed based on a non conventional process of electrical pulse discharge in a water chamber, referred to as 'Pulse Electrohydrodynamic Technology' (PELHYDT). The application of the PELHYDT in sewer blockage removal is presented in this paper. Existing machinery can remove two blockages of gully pot connections per hour. Three blockages of pipe conduits are generally removed during an 8-h working day. Applying PELHYDT technology, which allows for high rates of removal of mechanical obstructions, it is possible to achieve operating fluid pressures in the order of 10(3)-10(4) bars, a velocity of 100 m/s, a deformation acceleration of the model material structure of 10(6)-10(7) m/s2, and high-frequency hydraulic shock waves with a frequency of 10(3)-10(4) Hz. The applicability of this efficient technology in sewer blockage removal was proven under laboratory conditions at operating fluid pressures from 50 to 160 bars, which are standard for sewer maintenance. Water velocities generally achieved in sewers using existing flushing technologies range between 1 and 3 m/s and usually do not exceed 9 m/s. PELHYDT creates waves whose velocity is at least 100 m/s, and is therefore about ten times more efficient than existing technologies. PELHYDT generates an electrohydrodynamic wave very quickly, virtually in the form of an explosion. It was proven under laboratory conditions that the application of this technology for blockage removal in practice will not result in any sewer damage. PMID- 22053464 TI - Diphasic transfer of oxygen in vertical flow filters: a modelling approach. AB - Oxygen renewal, as a prominent phenomenon for aerobic bacterial activity, deeply impacts vertical flow constructed wetland (VFCW) treatment efficiency. The authors introduce a multiphase model able to simulate oxygen transfer in VFCWs. It is based on a two-phase flow module, and a transport module. The transport module is able to deal with convection/diffusion phenomena, inter-phase (air water) mass exchange, and first-order kinetics. The first results displayed for the air phase allow us to draw the following ideas on the design of vertical filters. The ponding phenomenon is more efficient for oxygen renewal than non ponding batch loading: it provides a higher value, sooner, and deeper in the filter. In non-colonised filters and for standard batch loading, oxygen convection in the air phase is predominant for oxygen renewal. The seepage front limits oxygen renewal through the bottom of the filter and leads to an insufficient oxygen concentration on the lowest part of the filter. PMID- 22053465 TI - A study on ruthenium-based catalysts for pharmaceutical wastewater treatment. AB - Ruthenium-based catalysts were prepared by a saturation-dip method. Their catalytic activity was evaluated by a catalytic wet oxidation (CWO) process. The ruthenium-based catalysts were used to purify organic pharmaceutical wastewater with high concentration pyridine and pyridine derivatives that have high chemical oxygen demand (COD). In the CWO process, organic pharmaceutical wastewater was continuously pumped into fixed-bed reactors filled with Ru-based catalysts, while the organic components in wastewater were catalytically degraded by oxygen at high temperatures and pressures (temperature, 170-300 degrees C; pressure, 1.0-10 MPa). The experimental results showed that the prepared catalysts could effectively purify pharmaceutical wastewater with high concentration organic components, which are difficult to degrade biochemically, and that the removal rates of both COD and total nitrogen were over 99%. PMID- 22053466 TI - The Cauvery river basin in southern India: major challenges and possible solutions in the 21st century. AB - India is facing major challenges in its water resources management (WRM) sector. Water shortages are attributed to issues such as an explosion in population, rapid urbanization and industrialization, environmental degradation and inefficient water use, all aggravated by changing climate and its impacts on demand, supply and water quality. This paper focuses on the contemporary and future situation in the Cauvery river basin in Southern India, shared by different states, predominantly Karnataka and Tamil Nadu. As water issues largely fall under the authority of the states, inter-state water disputes have a long tradition in the Cauvery river basin. Future changes in precipitation during the two monsoon seasons will only increase these tensions. Both states depend on the arrival of these monsoon rains to water their crops and to replenish the groundwater. The paper identifies the major challenges and general possible solutions for sustainable WRM within the river basin. It synthesises the relevant literature, describes practices that should be addressed in the scope of integrated WRM--including water availability increase and demand management--and stresses the need for further quantitative analyses. PMID- 22053467 TI - Quantification of sewer leakage by a continuous tracer method. AB - Water authorities interested in the evaluation of the structural state of a sewer must quantify leakage to plan strategic intervention. However, the quantification of the exfiltration and the localisation of structural damage are challenging tasks that usually require expensive and time-consuming inspections. Herein, we report one of the first applications of the QUEST-C method to quantify the exfiltration in a continuously operating sewer by dosing two chemical tracers, sodium bromide (NaBr) and lithium chloride (LiCl). The method was applied at the catchment scale in a 14-year-old sewer in Rome, Italy. Preliminary laboratory tests, field measurements, and numerical simulations showed that reliable results require the QUEST-C method to be applied to sewers without lateral inflows, during periods of quasi-steady flow, and that the travel time of the NaBr tracer is minimised. Three sewer reaches were tested and the estimated exfiltration, as a fraction of the dry weather flow (DWF), increased from 0.128 in the agricultural area to 0.208 in the urban area. Although our estimates are at the lower end of the range given in the literature (0.01-0.56 DWF), the exfiltration was not negligible, and interventions should focus on the sewers in urban areas. This illustrates the capability of the QUEST-C method to guide strategic intervention at low cost and without an interruption of sewer operation. However, careful interpretation of the results is recommended for sewers with many lateral inflows, where leakage may be overestimated. PMID- 22053468 TI - Particle counting as a tool to predict filterability in membrane bioreactors activated sludge? AB - Activated sludge quality is one of the major factors influencing flux decline in membrane bioreactors (MBRS). Sludge filterability is a recognized parameter to characterize the physical properties of activated sludge. Decrease in filterability is linked to a higher number of submicron particles. In our present research we studied whether particle counting techniques can be used to indicate deflocculation of the sludge suspended fraction to submicron particles, causing the aforementioned filterability decrease. A total number of 105 activated sludge samples were collected in four full scale municipal MBRS. Samples were tested for filterability and particle counting in the range 2-100 microm. In 88% of the membrane tank samples the filterability varied between good and poor, characterized by the deltaR20, being 0 < deltaR20 < 1. Filterability varied following the season of the year, stability of the MBR operation and recirculation ratio. The membrane tank filterability can be improved by applying low recirculation ratio between MBR tanks. The applied particle counting methodology generated reproducible and reliable results in the range 10-100 microm. Results show that differences in filterability cannot be explained by variations in particle size distribution in the range 10-100 microm. However, measurable deflocculation might be masked by the large numbers of particles present. Therefore, we cannot exclude the suspended particles as a possible source of submicron particles that are subsequently responsible for MBR sludge filterability deterioration. PMID- 22053469 TI - Treatment of linear alkylbenzene sulfonate (LAS) wastewater by internal electrolysis--biological contact oxidation process. AB - Surfactant wastewater is usually difficult to treat due to its toxicity and poor biodegradability. A separate physico-chemical or biochemical treatment method achieves a satisfactory effect with difficulty. In this study, treatment of the wastewater collected from a daily chemical plant by the combination processes of Fe/C internal electrolysis and biological contact oxidation was investigated. For the internal electrolysis process, the optimal conditions were: pH = 4-5, Fe/C = (10-15):1, air-water ratio = (10-20):1 and hydraulic retention time (HRT)= 2 h. For the biological contact oxidation process, the optimal conditions were: HRT = 12 h, DO = 4.0-5.0 mg/L. Treated by the above combined processes, the effluent could meet the I-grade criteria specified in Integrated Wastewater Discharge Standard of China (GB 8978-1996). The results provide valuable information for full-scale linear alkylbenzene sulfonate wastewater treatment. PMID- 22053470 TI - Aerobic granulation in a mechanical stirred SBR: treatment of low organic loads. AB - Aerobic granular sludge was produced in a sequencing batch reactor (SBR) characterized by a height to diameter ratio of 2.5 and the use of mechanical stirring. Compact and regular aerobic granules of up to 1.75 mm of average diameter were formed in the reactor with an organic loading rate of 1.75 kg COD/(m3 d). Settling properties of the obtained aggregates were: sludge volumetric index of 30-40 mL/g VSS and settling velocity higher than 8 m/h. The effects of different carbon to nitrogen ratios (TOC/N) in the feeding on the organic matter oxidation and nitrification process were studied. The concentration of organic matter in the feeding was stepwise reduced (from 190.0 to 37.5 mg TOC/L) and ammonium increased (from 25 to 50 mg NH4+ -N/L). TOC/N ratios of 7.50, 3.00, 1.50 and 0.75 g/g in the feeding were tested. The TOC removal percentage was around 80-95% during the whole operational period and the N removal percentages obtained in the reactor were up to 40%, however, physical properties of the granules were not maintained. PMID- 22053471 TI - Variation of algal viability during electrochemical disinfection using Ti/RuO2 electrodes. AB - This paper studied the influence of the operating conditions, e.g., current density, electrolyte and exposure time, on the variation of the algal viability during electrochemical disinfection processes. An electrochemical tube employing Ti/RuO2 as anodes was constructed for inactivation of cyanobacteria (often called blue-green algae) Microcystis aeruginosa. Viability of algal cells was determined by 2,3,5-triphenyl-tetrazoliumchloride (TTC) dehydrogenase activity assay and neutral red (NR) staining assay. Algal suspensions with cell density of 5-7 x 10(9) L(-1) were exposed to current densities from 1 to 8 mA cm(-2) at room temperature (25-30 degrees C) for 30 min. The results showed that the cell viability decreased obviously with the increase of current density. After exposure to 4 mA cm(-2) for more than 7 min, Microcystis aeruginosa didn't have the ability to resume growth. Comparative disinfection tests with different electrolytes were conducted, including chlorides, sulfates, nitrates and phosphates. Microcystis aeruginosa appeared to be sensitive to electro-generated chlorine oxidants. The inactivation effect was also demonstrated to occur in chlorine-free electrolytes. However, decrease of the inactivation effect by adding ascorbic acid as an oxidant scavenger indicated that the reactive oxygen species, especially *OH radicals, played an important role for chlorine-free electrolytes. PMID- 22053472 TI - Characterization of dissolved organic matter from Australian and Chinese source waters by combined fractionation techniques. AB - The character of dissolved organic matter (DOM) in source waters from two countries (Australia and China) was investigated using an extended fractionation technique by combining resin adsorption, ultrafiltration and high performance size exclusion chromatography. There are distinctive chemical characteristics associated with DOM origins. Australian sourced DOM had higher hydrophobic acid (HoA) content and exhibited a more pronounced humic character, indicating a higher influence from allochthonous organics (decayed plant bodies from vegetated catchments). The higher content of hydrophobic base and neutral components found in Chinese DOM, may be attributed to the effects of increasing pollution caused by the rapid urbanization in China. The molecular weights (MWs) of aquatic HoA are predominantly in the moderate (e.g., 1-10 kDa) or small (e.g., < 1 kDa) ranges. This suggests that aquatic HOA should not be assumed as high MW organics without experimental validation. It is also found that some of the low MW compounds in our samples were hydrophobic, which could explain the observation of low MW organic compounds being able to be removed by conventional treatment processes. PMID- 22053473 TI - Nutrient loads and their impacts on chlorophyll a in the Mae Klong River and estuarine ecosystem: an approach for nutrient criteria development. AB - Investigations on the water quality of the Mae Klong River and Estuary were conducted from April 2005 to February 2006 during periods of early-, mid-, and late-loading. Nutrient loads and transfer patterns were studied together with clarification of contaminated sites. The results indicated that NH4+, NO2- + NO3 , Si(OH)4 and PO4(3-) concentrations varied by season and were comparatively high in the mid-loading period. Analysis of DIN:P and Si:P molar ratios indicated that P04(3-) could possibly be a limiting nutrient. Highly contaminated sites were in the middle (Ratchaburi province) and lower (Samut Songkhram province) river zones in which anthropogenic wastewater discharges were significantly (p < 0.05) loaded. Analysis of the DIN and P transfer patterns showed that self-remediation efficiencies were rarely found. The highest DIN and P loads of 23.87 and 4.03 t/day, respectively, were found in Samut Songkhram province. Nutrients were found to contribute to the hypertrophic condition of the lower river and the estuary. The baseline level of chlorophyll a in the upper river was approximately 3.3 microg/L, while levels exceeded 10 microg/L in the estuarine zone. Such chlorophyll a levels were highly significant (p < 0.01) related to DIN and P (with correlation coefficients of 0.44 and 0.37, respectively). In order to maintain river conservation to an acceptable degree, levels of about 20 micromol/L DIN and 1 micromol/L P were suggested as the upper limits. To achieve such levels will require serious consideration with regard to the development of nutrient criteria for water resource conservation management and sustainable utilization purposes. PMID- 22053474 TI - Analysis of shear stress and energy consumption in a tubular airlift membrane system. AB - Application of a two-phase slug flow in side-stream membrane bioreactors (MBRs) has proven to increase the permeate flux and decrease fouling through a better control of the cake layer. Past literature has shown that the hydrodynamics near the membrane surface have an impact on the degree of fouling by imposing high shear stress near the surface of the membrane. Previously, shear stress histograms (SSH) have been introduced to summarize results from an experimental setup developed to investigate the shear stress imposed on the surface of a membrane under different two-phase flow conditions (gas and liquid) by varying the flow of each phase. Bimodal SSHs were observed, with peaks corresponding to the shear induced by the liquid and gas flow respectively. In this contribution, SSHs are modelled using simple empirical relationships. These are used to identify the two-phase flow conditions that optimize fouling control. Furthermore, the total energy consumption of the system was estimated based on the two-phase pressure drop. It was found that low liquid and high gas flow rates (ratio of approx. 4) balanced the peaks and minimized the energy consumption. PMID- 22053475 TI - Phosphorus removal using nanofiltration membranes. AB - A high concentration of phosphorus in wastewater may lead to excessive algae growth and deoxygenation of the water. In this work, nanofiltration (NF) of phosphorus-rich solutions is studied in order to investigate its potential in removing and recycling phosphorus. Wastewater samples from a pulp and paper plant were first analyzed. Commercial membranes (DK5, MPF34, NF90, NF270, NF200) were characterized and tested in permeability and phosphorus removal experiments. NF90 membranes offer the highest rejection of phosphorus; a rejection of more than 70% phosphorus was achieved for a feed containing 2.5 g/L of phosphorus at a pH <2. Additionally, NF90, NF200 and NF270 membranes show higher permeability than DK5 and MPF34 membranes. The separation performance of NF90 is slightly affected by phosphorus concentration and pressure, which may be due to concentration polarization and fouling. By adjusting the pH to 2 or adding sulfuric acid, the separation performance of NF90 was improved in removing phosphorus. However, the presence of acetic acid significantly impairs the rejection of phosphorus. PMID- 22053476 TI - Screening of organic contaminants in urban snow. AB - Snowmelt is known to cause peak concentrations of pollutants, which may adversely affect receiving water quality. High concentrations of metals and suspended solids in snow have been reported, whereas studies on organic pollutants are rare. This study aims at investigating the occurrence of anthropogenic organic compounds in urban snow in Gothenburg (Sweden). The most frequently detected organic pollutants in the collected snow samples were polycyclic aromatic hydrocarbons (PAHs), high molecular-weight phthalates, 4-nonylphenol and 4-t octylphenol. Brominated flame retardants and chlorinated paraffins were only sporadically detected. In several snow samples, the concentrations of specific PAHs, alkylphenols and phthalates were higher than reported stormwater concentrations and European water quality standards. Pollutant source identification and sustainable management of snow are important instruments for the mitigation of organic contaminants in the urban environment. PMID- 22053477 TI - Treatment of slaughterhouse plant wastewater by using a membrane bioreactor. AB - The use of a membrane bioreactor (MBR) for removal of organic substances and nutrients from slaughterhouse plant wastewater was investigated. The chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) concentrations of slaughterhouse wastewater were found to be approximately 571 mg O2/L, 102.5 mg/L, and 16.25 mg PO4-P/L, respectively. A submerged type membrane was used in the bioreactor. The removal efficiencies for COD, total organic carbon (TOC), TP and TN were found to be 97, 96, 65, 44% respectively. The COD value of wastewater was decreased to 16 mg/L (COD discharge standard for slaughterhouse plant wastewaters is 160 mg/L). TOC was decreased to 9 mg/L (TOC discharge standard for slaughterhouse plant wastewaters is 20 mg/L). Ammonium, and nitrate nitrogen concentrations of treated effluent were 0.100 mg NH4-N/L, and 80.521 mg NO3-N/L, respectively. Slaughterhouse wastewater was successfully treated with the MBR process. PMID- 22053478 TI - Beneficial effects on water management of simple hydraulic structures in wetland systems: the Vallevecchia case study, Italy. AB - Conflicting water uses in coastal zones demand integrated approaches to achieve sustainable water resources management, protecting water quality while allowing those human activities which rely upon aquatic ecosystem services to thrive. This case study shows that the creation and simple management of hydraulic structures within constructed wetlands can markedly reduce the non-point pollution from agriculture and, simultaneously, benefit agricultural activities, particularly during hot and dry periods. The Vallevecchia wetland system is based on a reclaimed 900 ha-large drainage basin in Northern Italy, where droughts recently impacted agriculture causing water scarcity and saltwater intrusion. Rainwater and drained water are recirculated inside the system to limit saltwater intrusion, provide irrigation water during dry periods and reduce the agricultural nutrient loads discharged into the bordering, eutrophic Adriatic Sea. Monitoring (2003-2009) of water quality and flows highlights that the construction (ended in 2005) of a gated spillway to control the outflow, and of a 200,000 m3 basin for water storage, dramatically increased the removal of nutrients within the system. Strikingly, this improvement was achieved with a minimal management effort, e.g., each year the storage basin was filled once: a simple management of the hydraulic structures would greatly enhance the system efficiency, and store more water to irrigate and limit saltwater intrusion. PMID- 22053479 TI - Recent operational experiences of FILMTEC NF270 membrane in Europe. AB - Nanofiltration (NF) is an attractive technology for potable and industrial water treatment because NF operates between ultrafiltration (UF) and reverse osmosis (RO) membranes. NF is designed to remove a high percentage of organic contaminants (humic acids, pesticides, color bodies) while passing a medium to high percentage of salt. Compared to UF membranes, the NF product water quality is significantly better; compared to comparable RO treatment systems NF systems require lower operating pressures. Due to these features, NF is increasingly used in a broad range of water treatment applications. The general applications include softening, as well as color, organics and micro-organism removal. DOW FILMTEC NF270-400 is one the most frequently used elements in water treatment and this paper presents examples of three recent NF270-400 installations in Europe. The first two plants, Eupen and Stembert, are located in Belgium and produce potable water from surface water. The third one is a Scandinavian plant which purifies groundwater for a brewery and soft drink production. The presented operation results prove NF to be a highly competitive technique for low cost water treatment. PMID- 22053480 TI - Determination of the optimal rate for the microaerobic treatment of several H2S concentrations in biogas from sludge digesters. AB - The treatment of H2S in the biogas produced during anaerobic digestion has to be carried out to ensure the efficient long-lasting use of its energetic potential. The microaerobic removal of H2S was studied to determine the treatment capacity at low and high H2S concentrations in the biogas (0.33 and 3.38% v/v) and to determine the optimal O2 rate that achieved a concentration of H2S of 150 mg/Nm3 or lower. Research was performed in pilot-plant scale digesters of sewage sludge, with 200 L of working volume, in mesophilic conditions with a hydraulic retention time of 20 d. O2 was supplied at different rates to the headspace of the digester to create the microaerobic conditions. The treatment successfully removed H2S from the biogas with efficacies of 97% for the low concentration and 99% for the highest, in both cases achieving a concentration below 150 mg/Nm3. An optimal O2 rate of 6.4 NLO2/Nm3 of biogas when treating the biogas was found with 0.33% (v/v) of H2S and 118 NLO2/ Nm3 of biogas for the 3.38% (v/v) concentration. This relation may be employed to control the H2S content in the biogas while optimising the O2 supply. PMID- 22053481 TI - The urban stormwater farm. AB - Currently more than 3 billion people live in urban areas. The urban population is predicted to increase by a further 3 billion by 2050. Rising oil prices, unreliable rainfall and natural disasters have all contributed to a rise in global food prices. Food security is becoming an increasingly important issue for many nations. There is also a growing awareness of both 'food miles' and 'virtual water'. Food miles and virtual water are concepts that describe the amount of embodied energy and water that is inherent in the food and other goods we consume. Growing urban agglomerations have been widely shown to consume vast quantities of energy and water whilst emitting harmful quantities of wastewater and stormwater runoff through the creation of massive impervious areas. In this paper it is proposed that there is an efficient way of simultaneously addressing the problems of food security, carbon emissions and stormwater pollution. Through a case study we demonstrate how it is possible to harvest and store stormwater from densely populated urban areas and use it to produce food at relatively low costs. This reduces food miles (carbon emissions) and virtual water consumption and serves to highlight the need for more sustainable land-use planning. PMID- 22053482 TI - Decision making in flood risk based storm sewer network design. AB - It is widely recognised that flood risk needs to be taken into account when designing a storm sewer network. Flood risk is generally a combination of flood consequences and flood probabilities. This paper aims to explore the decision making in flood risk based storm sewer network design. A multiobjective optimization is proposed to find the Pareto front of optimal designs in terms of low construction cost and low flood risk. The decision making process then follows this multi-objective optimization to select a best design from the Pareto front. The traditional way of designing a storm sewer system based on a predefined design storm is used as one of the decision making criteria. Additionally, three commonly used risk based criteria, i.e., the expected flood risk based criterion, the Hurwicz criterion and the stochastic dominance based criterion, are investigated and applied in this paper. Different decisions are made according to different criteria as a result of different concerns represented by the criteria. The proposed procedure is applied to a simple storm sewer network design to demonstrate its effectiveness and the different criteria are compared. PMID- 22053483 TI - Cd, Cu and Zn mobility in contaminated sediments from an infiltration basin colonized by wild plants: the case of Phalaris arundinacea and Typha latifolia. AB - Infiltration basins are shallow reservoirs in which stormwater is temporarily collected in order to reduce water volume in downstream networks. The settling of stormwater particles leads to a contaminated sediment layer. Wild plants can colonize these basins and can also play a role on the fate of heavy metals either directly by their uptake or indirectly by modification of physico-chemical characteristics of the sediment and therefore by modification of the mobility of heavy metals. The aim of this study, carried out in a vegetated infiltration basin, is to assess Cd, Cu and Zn mobility in two zones colonized by different species, Phalaris arundinacea and Typha latifolia. The study was carried out using three single chemical extractions: CaCl2 for the exchangeable phase, acetate buffer for the acido-soluble fraction and diethylenetriamine-pentaacetic acid (DTPA) for the fraction associated to the organic matter. Zn and Cd are mainly associated to carbonated and organic matter phases of the sediment. Moreover, acetate buffer-extractable Zn contents are strongly correlated to carbonates content in the sediment. DTPA-extractable Cu contents are strongly correlated with organic carbon sediment contents. We have also noted that extractable contents were significantly different between both zones whatever the metal. PMID- 22053484 TI - Measurement of flow velocity profiles in tank structures using the prototype device OCM Pro LR. AB - Generally, studies investigating the treatment efficiency of tank structures for storm water or waste water treatment observe pollutant flows in connection with conditions of hydraulic loading. Further investigations evaluate internal processes in tank structures using computational fluid dynamic (CFD) modelling or lab scale tests. As flow paths inside of tank structures have a considerable influence on the treatment efficiency, flow velocity profile (FVP) measurements can provide a possibility to calibrate CFD models and contribute to a better understanding of pollutant transport processes in these structures. This study focuses on tests carried out with the prototype FVP measurement device OCM Pro LR by NIVUS in a sedimentation tank with combined sewer overflow (CSO) situated in Petange, Luxembourg. The OCM Pro LR measurement system analyses the echo of ultrasonic signals of different flow depths to get a detailed FVP. A comparison of flow velocity measured by OCM Pro LR with a vane measurement showed good conformity. The FVPs measured by OCM Pro LR point out shortcut flows within the tank structure during CSO events, which could cause a reduction of the cleaning efficiency of the structure. The results prove the applicability of FVP measurements in large-scale structures. PMID- 22053485 TI - Inflow based investigations on the efficiency of a lamella particle separator for the treatment of stormwater runoffs. AB - The present design of stormwater tanks is based on the creation of storage volume to retain stormwater and the prevention or reduction of stormwater overflows. The treatment of stormwater is often improved with mechanical equipment. The general layout rules do usually not include the appropriate choice of design inflow related to the chosen treatment equipment. In the following investigations it was the task to analyze the hydraulic efficiency and the overflow behaviour of a lamella particle separator inside a stormwater tank under different design approaches regarding the chosen design inflow. Therefore six scenarios with different precipitation yield approaches were chosen and applied to a given constant sized catchment to calculate the design inflows. For a given minimum particle size, the necessary number of lamellas were determined for the scenarios and standard stormwater tanks were dimensioned. These stormwater tanks were modelled in the hydrologic model SMUSI to investigate the overflow behaviour of the different tank sizes. The number of overflow events, their duration and maximum flow rates were the results of the modelling. Comparisons to the design inflows were carried out. The treated particles sizes at the overflow events were determined reversible and compared to the original chosen minimum particle sizes. PMID- 22053486 TI - A new approach to energy-efficient treatment of wastewater produced by the fish industry in Vietnam. AB - Economic growth in Vietnam in the last few years has brought about an increasing demand for energy and has had a severe environmental impact. Fish processing is one of the fastest-growing industries that discharge organically-polluted wastewater. To counter these environmental problems, new technologies for energy efficient treatment are needed. By coupling innovative nitrogen removal systems with anaerobic treatment processes, it is possible to realise such technologies. In the present project, a combined deammonification and anaerobic carbon removal system is presented. Special requirements to enable reliable treatment are discussed, taking industrial wastewater characteristics into consideration. To evaluate energetic efficiency, energy balance calculations based on data from a fish-processing factory are made. The determined specific energy consumption and production rates show that energy recovery is possible, even when COD and nitrogen removal efficiencies of over 90% are achieved. Depending on the pre treatment employed, energy recovery rates ranging from 0.6 to 2.5 kWh/mt raw fish can be reached. PMID- 22053487 TI - Preparation and characterization of CTAB-HACC bentonite and its ability to adsorb phenol from aqueous solution. AB - A novel type of adsorbent was prepared by modifying bentonite with N-2 hydroxypropyl trimethyl ammonium chloride chitosan (HACC) with cetyl trimethylammonium bromide (CTAB). The adsorbent was named CTAB-HACC bentonite. Its characteristics were investigated using thermogravimetric, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction. The adsorption of phenol onto CTAB-HACC bentonite was evaluated by changing various parameters, such as contact time, adsorbent dosage, initial pH of the solution, and temperature. The maximum adsorption was observed at pH 12. Adsorption of phenol on CTAB-HACC bentonite favored at lower temperature and established the equilibrium in 30 min. The adsorption efficiency reached 82.1%, and the adsorption capacity was 7.12 mg/g from the phenol solution with a concentration of 500 mg/L at pH 12.0 and 20 degrees C. PMID- 22053488 TI - Anaerobic biodegradation of 2,4,6-trichlorophenol in expanded granular sludge bed and fluidized bed biofilm reactors bioaugmented with Desulfitobacterium spp. AB - The biodegradation of 2,4,6-trichlorophenol (246TCP) was studied using expanded granular sludge bed (EGSB) reactors and a fluidized bed biofilm reactor (FBBR) filled with activated carbon. One of the EGSB reactor and the FBBR were bioaugmented with Desulfitobacterium strains. 246TCP loading rate was gradually incremented from 10 to 250 mg L(-1) day(-1). The main pathway of dechlorination was in ortho-position, generating 4-chlorophenol and 2,4-dichlorophenol. The maintenance of both COD degradation efficiency (higher than 80%) and methanogenic efficiency (between 0.3 and 0.6 g CH4-COD g(-1) COD consumed) in EGSB reactor implies a great stability of the process. Through isotherm studies in FBBR, it could be deduced that around 52% of 246TCP was completely dechlorinated, whereas the adsorption involved around 16%. By means of FISH studies it was proved that the methanogenic Archaea community was maintained in the bioaugmented EGSB reactor, whereas in the FBBR this community was gradually developed until reaching stability. Desulfitobacterium community was also maintained in the reactors, although D. chlororespirans proportion rise in the FBBR at the higher 246TCP loading rates, implying that this species can withstand the 246TCP toxicity better than D. hafniense. PMID- 22053489 TI - The challenge of documenting water quality benefits of conservation practices: a review of USDA-ARS's conservation effects assessment project watershed studies. AB - The Conservation Effects Assessment Project was established to quantify water quality benefits of conservation practices supported by the U.S. Department of Agriculture (USDA). In 2004, watershed assessment studies were begun in fourteen agricultural watersheds with varying cropping systems, landscapes, climate, and water quality concerns. This paper reviews USDA Agricultural Research Service 'Benchmark' watershed studies and the challenge of identifying water quality benefits in watersheds. Study goals included modeling and field research to assess practices, and evaluation of practice placement in watersheds. Not all goals were met within five years but important lessons were learned. While practices improved water quality, problems persisted in larger watersheds. This dissociation between practice-focused and watershed-scale assessments occurred because: (1) Conservation practices were not targeted at critical sources/pathways of contaminants; (2) Sediment in streams originated more from channel and bank erosion than from soil erosion; (3) Timing lags, historical legacies, and shifting climate combined to mask effects of practice implementation; and (4) Water quality management strategies addressed single contaminants with little regard for trade-offs among contaminants. These lessons could help improve conservation strategies and set water quality goals with realistic timelines. Continued research on agricultural water quality could better integrate modeling and monitoring capabilities, and address ecosystem services. PMID- 22053490 TI - Acute trust finance: NHS giants sound warning and defy 'suspicion' to ask for more. PMID- 22053491 TI - 'All' elite trusts face 'dumbing down' threat. PMID- 22053492 TI - The wrong kind of integration. PMID- 22053493 TI - This marriage is going to take work. PMID- 22053494 TI - Leadership: Two's company. PMID- 22053495 TI - Electronic discharge: Don't leave empty handed. PMID- 22053496 TI - Workforce: Game changer. PMID- 22053497 TI - Efficiency: Powerful change for pathology. PMID- 22053498 TI - Protecting breastfeeding through implementation of the International Code: what's law got to do with it? PMID- 22053499 TI - The decision not to initiate breastfeeding--women's reasons, attitudes and influencing factors--a review of the literature. AB - Breastfeeding is the biological feeding norm for human babies. Encouraging breastfeeding is a primary health promotion strategy, with studies demonstrating the risks of artificial baby milks. Each year approximately 10% of the women who give birth in New South Wales decide not to initiate breastfeeding, and the demographic characteristics of this group of women have previously been identified. This paper reviews the literature to explore the factors that influence women's decisions about breastfeeding, and their reasons for not initiating breastfeeding. The review revealed there are relatively few studies that explore the experiences of women who decide not to initiate breastfeeding, especially in the Australian context. PMID- 22053500 TI - Mechanisms behind breastmilk's protection against, and artificial baby milk's facilitation of, diarrhoeal illness. AB - It is well known that exclusive breastfeeding provides protection against diarrhoeal infection, but the mechanisms behind this protection are poorly understood. In addition, it is well known that feeding a baby artificial baby milk dramatically increases the risk of diarrhoeal illness severe enough to require medical treatment, including hospitalisation, but the mechanisms by which artificial baby milk facilitates infection are largely unrecognised. This paper uses non-technical language to describe some of the known ways in which breastmilk provides infants with external immune support. Detailed knowledge of the importance of breastfeeding and the risks associated with the use of artificial baby milk will assist more mothers to exclusively breastfeed. PMID- 22053501 TI - HSJ roundtable: procurement: It's time to use our muscle. PMID- 22053502 TI - Outsourcing: Clean out the waste. PMID- 22053503 TI - Research: Do as the Romans did. PMID- 22053504 TI - Workforce: Pool of talent. PMID- 22053505 TI - Case studies: Ready for a big shift. PMID- 22053506 TI - Reducing unwarranted variation: Turn left for a better service. PMID- 22053507 TI - Reducing variation: cancer: Breast op and home in one day. PMID- 22053508 TI - Reducing variation: heart: Modelling helps to prove blood test value. PMID- 22053509 TI - Reducing variation: diagnostics: from 20 weeks to just 14 days. PMID- 22053510 TI - Reducing variation: lung: Cash saved on unnecessary oxygen. PMID- 22053511 TI - Value for money: Fit to negotiate. PMID- 22053512 TI - Case studies: The price is right. PMID- 22053513 TI - Equipment rationalisation: Don't forget your kit. PMID- 22053514 TI - Case studies: We have the technology. PMID- 22053515 TI - Barriers to PCP access send patients to EDs. PMID- 22053516 TI - More Medicare cuts possible in debt deal. PMID- 22053517 TI - Medicine on the move: wireless computing inside & outside your practice. PMID- 22053518 TI - 6 tips for improving your negotiating skills: learn how to bargain so that all parties to the deal come away satisfied. PMID- 22053519 TI - Getting no respect: slights, real and imagined, most often cause patients to leave their doctors. PMID- 22053520 TI - Excel at collections: strategies for successful time-of-service payments. PMID- 22053521 TI - New characters on the block: quick response codes can enhance patient communication, education, and marketing. PMID- 22053522 TI - One-touch access to a world of resources: mobile health apps streamline workflows. PMID- 22053523 TI - Exam room check-out aids convenience, privacy: patient, staff satisfaction improve when process changes. PMID- 22053524 TI - Paying close attention can lead to a rare find: a physician discovers a true zebra case in one patient. PMID- 22053525 TI - Gender policy developments and policy regimes in 22 OECD countries, 1979-2008. AB - This study investigates trends and clustering of gender policy in 22 OECD (Organization for Economic Cooperation and Development) countries during 1979 2008. The starting point was Sainsbury's gender policy regime framework, and the study included indicators reflecting the male bread-winner, individual earner carer, and separate gender roles regimes. The indicators were followed over seven time points for mean, range, and distribution. Cluster analyses were performed for the years 1979, 1989, 1999, and 2004. In accordance with previous studies, the authors found a Nordic cluster of earner-carer countries, while several Southern European countries and the United States were marked by their low generosity and high pension requirements. Though aspects of the separate gender roles regime have become more widespread, no country could be classified as fully belonging to this regime type. The two aspects of the model--compensatory measures in the pension system, and benefits for caring activities--were never present simultaneously. PMID- 22053526 TI - Employment precariousness in Spain: prevalence, social distribution, and population-attributable risk percent of poor mental health. AB - As a consequence of labor market flexibilization, nonstandard employment has expanded and standard employment has declined. In many cases, these transformations are best described as an evolution toward precarious employment, which is considered a major determinant of health and health inequalities. Using the Employment Precariousness Scale (EPRES), this study aims to determine the prevalence of precarious employment in the waged and salaried workforce in Spain, to describe its distribution across social groups defined by occupational class, gender, age, and immigrant status, and to estimate the proportion of cases of poor mental health potentially attributable to employment precariousness. Data are from the Psychosocial Work Environment Survey conducted in 2004-5 on a representative sample of the Spanish workforce. Findings indicate a high prevalence of employment precariousness, affecting nearly 6.5 million workers, with almost 900,000 of them exposed to high precariousness. These estimates are higher than the proportion of fixed-term employment reported in regular statistical sources but may today be an underestimation, given the current economic crisis. Additionally, a significant proportion of cases of poor mental health are potentially attributable to employment precariousness. Both the proportion of cases of poor mental health attributable to and the prevalence of employment precariousness were highly unequally distributed across the study sample, indicating that this may be a significant contributor to social inequalities in mental health. PMID- 22053527 TI - The impact of public employment on health and health inequalities: evidence from China. AB - Because the public and private sectors often operate with different goals, individuals employed by the two sectors may receive different levels of welfare. This can potentially lead to different health status. As such, employment sector offers an important perspective for understanding labor market outcomes. Using micro-level data from a recent Chinese household survey, this study empirically evaluated the impact of employment sector on health and within-sector health inequalities. It found that public sector employment generated better health outcomes than private sector employment, controlling for individual characteristics. The provision of more job security explained an important part of the association between public sector employment and better health. The study also found less health inequality by social class within the public sector. These findings suggest that policymakers should think critically about the "conventional wisdom" that private ownership is almost always superior, and should adjust their labor market policies accordingly. PMID- 22053528 TI - Social health insurance: to each according to his needs; from each according to his means--but what might that mean? AB - Despite the substantial literature on the financing and benefit incidence of social health insurance, the principles underlying such schemes are little debated. This article examines one of these key principles: to each according to his needs; from each according to his means. The authors discuss both sides of this principle at a conceptual level. On the needs side, they examine the issue of vertical equity. The approach of "communitarian claims" is proposed, both for eliciting the components of need and for determining the relative weights to be attached to the vertical dimensions of equity in health service delivery. On the means side, the authors also look to communitarian claims to assist in determining who should bear what burden in paying for social health insurance. They argue that with respect to the concept of "from each according to his means," it is useful to incorporate an element of willingness to pay, but meaning here the community's willingness to pay. PMID- 22053529 TI - Class divisions and health chances in Brazil. AB - This article analyzes the association between class divisions and health chances in the Brazilian population. It uses data from the health supplement of the 2008 National Household Survey. Multiple logistic regression models are estimated to determine the relation between social class and self-rated health status. This empirical investigation of health inequalities combines two modalities for social class comparison, thus benefiting from the potential utility of each. On the one hand, socioeconomic inequalities in health are analyzed with reference to the combination of two main assets, capital and expert knowledge, which generate material and health advantages in Brazil. The results demonstrate that social class measurements for Brazil capture a source of variation in health chances among social groups that is independent of education and family income. On the other hand, the use of theoretically univocal categories for exploring diversified class contrasts offers some explanatory starting points for health inequalities in the Brazilian population. PMID- 22053530 TI - Federalism and decentralization: impact on international and Brazilian health policies. AB - This article discusses the implications of decentralization in the light of international and Brazilian federalism, and its effects on public health policy. In a comparative analysis among countries, the authors find there is no single model; rather, each country has a unique structure of institutions and norms that have important implications for the operation of its health system. Brazil shares some similarities with other countries that have adopted a decentralized system and is assuming features ever closer to U.S. federalism, with a complex web of relationships. The degree of inequality among Brazilian municipalities and states, along with the budgetary imbalances caused by the minimal levels of resource utilization, undermines Brazil's constitutional principles and, consequently, its federalism. To ensure the constitutional mandate in Brazil, it is essential, as in other countries, to create a stable source of funds and increase the volume and efficiency of spending. Also important are investing in the training of managers, improving information systems, strengthening the principles of autonomy and interdependence, and defining patterns of cooperation within the federation. PMID- 22053531 TI - Ownership, financing, and management strategies of the ten largest for-profit nursing home chains in the United States. AB - This study examined the ownership, financing, and management strategies of the 10 largest for-profit nursing home chains in the United States, including the four largest chains purchased by private equity corporations. Descriptive data were collected from Internet searches, company reports, and other sources for the decade 1998-2008. Since 1998, the largest chains have made many changes in their ownership and structure, and some have converted from publicly traded companies to private ownership. This study shows the increasing complexity of corporate nursing home ownership and the lack of public information about ownership and financial status. The chains have used strategies to maximize shareholder and investor value that include increasing Medicare revenues, occupancy rates, and company diversification, establishing multiple layers of corporate ownership, developing real estate investment trusts, and creating limited liability companies. These strategies enhance shareholder and investor profits, reduce corporate taxes, and reduce liability risk. There is a need for greater transparency in ownership and financial reporting and for more government oversight of the largest for-profit chains, including those owned by private equity companies. PMID- 22053532 TI - The rise, decline, and future of the Swedish left. AB - Swedish voters' support for the labor movement has decreased from about 50 percent to less than 40 percent in recent decades, with a resulting loss of the majority in parliament. Over the same period, capitalism has undergone profound changes--transfer of production across borders, the huge growth and ultra-rapid movement of financial capital, and subordination of social welfare to the interests of profit. A new phase in the development of capitalism can be detected: from welfare capitalism to financial capitalism. Large parts of the public sector have been privatized by both conservative and labor governments, even while retaining public funding. The social gaps grow, and a new line of conflict is emerging in the values and interests that should govern care-taking, schools, and living conditions. The labor movement's ideological and scientific analyses have taken a backseat to liberal-conservative think tanks. An effective response to financial capitalism, transnational production chains, and European integration will require trade union and political actions across national borders to strengthen the power resources in the hands of the majority of the population, so as to counter the increasingly destructive powers of capitalism. PMID- 22053533 TI - Italian public health care organizations: specialization, institutional deintegration, and public networks relationships. AB - The Italian National Health Service (INHS) has undergone profound changes over the past three decades. With establishment of the INHS in 1978--a tax-based public health care system with universal coverage--one of the underlying principles was integration. The recognition of health and health care as requiring integrated answers led to the creation of a single public organization, the Local Health Unit, responsible for the health status of the population of its catchment area. At the beginning of the 1990s, the scenario radically changed. The creation of hospital trusts, the development of quasi-market mechanisms and management control tools, the adoption of a prospective payment system for reimbursing health care providers--all were signs of deintegration and institutional unbundling. Two structural changes have deeply sustained this deintegration: patients' empowerment and the increased possibilities for outsourcing practices. In more recent years, a new reintegration effort has occurred, often led by regional governments and based on institutional cooperation and network relationships. However, the earlier structural changes require innovative approaches and solutions if public health care organizations want to retain their leading role. PMID- 22053534 TI - Morphological adaptation to climate in modern Homo sapiens crania: the importance of basicranial breadth. AB - The aim of this study is to investigate whether the variation in breadth of the cranial base among modern human populations that inhabit different regions of the world is linked with climatic adaptation. This work provides an examination of two hypotheses. The first hypothesis is that the correlation between basicranial breadth and ambient temperature is stronger than the correlation between temperature and other neurocranial variables, such as maximum cranial breadth, maximum neurocranial length, and the endocranial volume. The second hypothesis is that the correlation between the breadth of the cranial base and the ambient temperature is significant even when other neurocranial features used in this study (including the size of the neurocranium) are constant. For the sake of this research, the necessary neurocranial variables for fourteen human populations living in diverse environments were obtained from Howells' data (except for endocranial volume which was obtained by means of estimation). The ambient temperature (more precisely, the mean yearly temperature) of the environments inhabited by these populations was used as a major climatic factor. Data were analysed using Pearson correlation coefficients, linear regression and partial correlation analyses. The results supported the two hypotheses, thus suggesting that ambient temperature may contribute to the observed differences in the breadth of the cranial base in the studied modern humans. PMID- 22053535 TI - Prevalence of torus palatinus and torus mandibularis in the Split-Dalmatian County, Croatia. AB - Torus palatinus (TP) and torus mandibularis (TM) are non-pathological outgrowths of unclear etiology that develop from the jaw bone. The purpose of the present study was to report on the prevalence, shape and location of TP and TM in the population of the Central Dalmatian region, Croatia. The study comprised of 1679 subjects, 985 females and 694 males, age range from 9 to 99 years who were examined by clinical examination and analysis of the plaster casts. Torus palatinus was found in 42.9% subjects and torus mandibularis in 12.6% of the subjects. Spindle-shaped torus palatinus was the most frequent type (45.6%). The most frequent type of torus mandibularis was bilateral solitary torus mandibularis (35.4%). Furthermore, torus palatinus was found in 40.1% of the total number of females and in 46.8% of the total number of males, indicating a significantly higher prevalence in the male population (p = 0.006). Torus mandibularis was found in 11.3% of the female population and in 14.6% of the male population, again indicating significantly higher prevalence in the male population (p = 0.046). The results of this study show significantly higher prevalence of torus palatinus and torus mandibularis in the male subjects. Furthermore, no differences in the prevalence of either TM or TP regarding age were found. PMID- 22053536 TI - Assessing psychosocial factors in depressed patients--accordance of patient's and physician's assessment. AB - Aim of this study was to investigate the differences in the assessment of psychosocial factors by depressed and non depressed patients, and their congruence with physicians' assessment for both groups. The cross-sectional study was conducted in three family physicians' practices in Zagreb, Croatia, during 2007. Sample of depressed patients included 76 patients out of 85, and randomized comparison group of 189 out of 235. Questionnaire recommended by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice was used for the assessment of psychosocial factors. Depressed patients significantly more frequently reported about social isolation (p(alone) = 0.013; p(close confident) = 0.005; p(help) = 0.001), family stress (p < 0.001), work stress (p(appropriate reward) = 0.029) and lower life satisfaction (p < 0.001) than non depressed. Their worse psychosocial functioning was noticed by family physicians who assessed social isolation (p(alone) = 0.013; p(close confident) = 0.032), family stress (p < 0.001) and life satisfaction (p < 0.001) significantly lower for depressed patients than for the random sample. Incongruence between family physicians and depressed patients assessment was valued by physicians to be of higher economic status (p < 0.001), and more intense family stress (p < 0.001). Assessment of psychosocial factors varied within the group of depressed patients and the random sample assessed either by themselves or by physicians. Congruence between family physicians and non depressed patients in the assessment of observed psychosocial factors was better than between physicians and depressed patients. PMID- 22053537 TI - The effect of dance over depression. AB - Dance and movement therapy are consisted of music, easy exercises and sensorial stimulus and provide drugless treatment for the depression on low rates. In this study, it has been aimed to examine the effect of dance over the depression. A total of 120 healthy male and female conservatory students ranged from 20 and 24 ages volunteered to participate in this study. They were divided randomly into 1 of 2 groups: dance training group (DTG; N = 60) and control group (CG; N = 60). A dance training program was applied to the subjects three days a week (Tuesday, Thursday, and Saturday) during 12 weeks. The subjects in the control group did not participate in the training and participated only in the pre and post test measurements. Beck Depression Scale was used for the pre and post test measurements of subjects. 12 weeks of dance training has been found to be effective on the depression levels of the subjects participating in the research as the training group (p < 0.05). The depression level of males and females before training has meaningfully decreased after 12 weeks of dance training (p < 0.05). When the depression levels of the subjects participated in research as the control group were separately evaluated for males and females, no meaningful change has been found in the depression levels during 12 weeks (p > 0.05). In conclusion, it has been seen that dance affects the depression levels of university students positively and decreases their depression levels. PMID- 22053538 TI - An example of qualitative research in social work with older people: the history of social work in old people's homes in Slovenia. AB - Social work with older people deals with improving their capacity and ability to face and resolve problems, and with raising awareness and encouraging their environment to maintain relational networks. Based on research regarding social work with older people this paper presents the historical aspect of older people's position within the development of institutional care for older people in Slovenia. The paper attempts to show some characteristics of care in institutions for older people in a historical perspective, considering the introductory description of older people's position in modern society, some characteristics of the (total) institution and a definition of the specifics of social work with older people. In the past the mission of the social worker in old people's homes was exclusively conceived on the basis of their relationship with the residents. Today, it is the administrative function that is more in the foreground. Regardless of the deviations seen in today's mission of social work as compared to the past, individual work with residents has always been and remains its characteristic today. Social workers help residents adapt to life in the home and the new institutional environment. They ensure that every individual's maximum abilities are considered, help solve the residents' problems, function as mediators in conflicts between the residents, and between the residents and staff. Therefore, social workers are expected to have certain abilities and characteristics and in order to be able to carry out quality work they need to participate in continuing education. PMID- 22053539 TI - Life satisfaction in persons of the third age after retirement. AB - The aim of this research was to determine the role of gender, type of residence, living arrangement, self-rated health status, loneliness, and sense of humor in self-reported life satisfaction in elderly retirees. The study included 300 elderly retirees from Zagreb, Croatia. Demographic data were collected with a structured questionnaire, whereas data on self-reported health status, loneliness, and sense of humor were collected with the UCLA Loneliness Scale, Life Satisfaction Index, HOPA-86, and SF-36 Health Survey. Participants living in a retirement home showed higher life satisfaction than those who lived in their own households. Those who had children showed greater life satisfaction No differences in life satisfaction were found with respect to gender, marital status, or living arrangement. The investigated demographic variables, self-rated health status, self-rated loneliness, and a sense of humor explained 52.8% of variance in life satisfaction. An active sense of humor was the most significant predictor. Living in a retirement home, having children, and having an active sense of humor had a positive influence on self-reported life satisfaction, whereas poorer self-rated health and loneliness had a negative influence. Taking into account the predictors of life satisfaction in preventive activities may contribute to successful aging. PMID- 22053540 TI - Influence of psychical trauma through transgenerational transfer on the development of traumatic reactions in women with diagnosed breast cancer. AB - Earlier experience of psychological trauma of a close person can through a transgenerational transfer influence traumatic reactions of a person going through a trauma at present, resulting in a repetition of earlier traumatic experiences and a development of a variety of mental disturbances. Purpose of our study was to evaluate the influence of transgenerational transfer on the development of Posttraumatic stress disorder (PTSD) in women with diagnosed breast cancer that had a family member with diagnosed cancer. The sample mainly consisted of 120 women treated in a Department of Oncology, Osijek University Hospital Center with diagnosis of newly discovered breast cancer, during the conduction of radio therapy having values Hamilton depression scale (HAM-D) from > or = 8 to < or = 24 or values Hamilton anxiety scale (HAM-A) from > or = 17 to < or = 30. Psychotherapeutic interview with a detailed clinical overview and with applying diagnostic criteria according to DSM-IV for mental disorders, specially structured non-standardized questionnaire for etiologic factors evaluation of the beginning of examinees' mental disorder, Los Angeles Symptom Checklist of PTSD symptoms (LASC), Hamilton's scale for anxiety evaluation (HAM-A) and Hamilton's scale for depression evaluation (HAM-D) were used. Results show that 61 (51%) of patients have a family member with diagnosed cancer. The average total value on LASC for examinees that had a family member with diagnosed cancer was slightly higher (22.92) in comparison to those who had no such family member (20.88). No statistically significant connection was found between having a family member with diagnosed cancer and the average total value on LASC. Although no connection was established between having a family member with diagnosed cancer and the average value on LASC in women with diagnosed breast cancer, transgenerational transfer of emotions seems to be important in their traumatic reactions, but it is still insufficiently researched and it is a challenge for future researches leaving many complicated issues open. PMID- 22053541 TI - A quality of life in chronic combat related posttraumatic stress disorder--a study on Croatian War veterans. AB - The main objective of this study was to examine an association of various symptoms in chronic combat-related post traumatic stress disorder (PTSD) and the quality of life in this population. 248 Croatian male war veterans all diagnosed with chronic PTSD were consecutively enrolled in this study as they showed up at the routine check-up. They were given self report questionnaires Trauma Symptom Inventory (TSI-A) evaluating different PTSD symptoms and WHO Quality of Life-BREF assessing four different domains of the quality of life. After independent sample t- test was performed, the presence of each symptom defined by Trauma Symptom Inventory indicated the impairment of all four quality of life domains in a group of subject suffering from it, except of intrusive experience not being associated with the lesser quality in social domain. All quality of life domains were significantly correlated with various PTSD symptoms; however Pearson correlation factors ranged from small to medium value. As expected, PTSD symptoms are associated with lesser quality of life in the affected population. The further research is needed to show possible causal relationship between PTSD and, especially, physical health of these patients. PMID- 22053542 TI - Health-related quality of life in the patients on maintenance hemodialysis: the analysis of demographic and clinical factors. AB - Health-related quality of life (HRQoL) among hemodialysis (HD) patients recently became a nephrologist's focus of interest. HRQoL is an important predictor of outcome in HD patients and need to be regularly assessed. The aim of the present study was to compare the HRQoL of chronic HD patients with general population and to analyze influencing sociodemographic and clinical factors. We included 255 prevalent HD patients from four dialysis centers. HRQoL was measured with The Medical Outcomes Study Short Form 36 Health Survey Questionnaire (SF-36). This data were compared with control group (N = 132) from the general Croatian population. Comparisons of SF-36 scale scores of HD patients regarding demographic and clinical factors (age, gender, education level, dialysis vintage and diabetes) were also performed and analyzed with a multivariate regression analysis. HRQoL in prevalent HD patients was relatively low (mean Physical Component Summary, PCS = 33.7, mean Mental Component Summary, MCS = 43.0) and was lower compared to the control group from the general population in all HRQoL domains, PCS and MCS scores. Almost 53% of the HD patients had the critical score PCS < 43 + MCS < 51 as the predictor of death and hospitalization. Better HRQoL was revealed in the patients < 65 years old, males, patients with higher educational level and in the patients on maintenance HD less than one year. Age was the only statistically significant predictor of PCS and MCS. Developments of HD technology, treatment of comorbidities, continuous patients' education, social and psychological support and use of other renal replacement modalities, especially kidney transplantation, may improve the HRQoL in these patients. PMID- 22053543 TI - Increasing smoking prevalence among pupils of several Croatian secondary medical schools between 1990 and 2006. AB - Smoking among pupils of secondary medical schools is of particular public health interest because of their role in the health system in the future. The study was part of the survey of smoking among students of Croatian medium medical schools. Data of 3 survey periods were available (1990-2002-2006). Specific smoking trends among 14-18 year olds were examined using odds ratios and multiple regressions. Sex ratios were calculated for each survey period. Daily smoking prevalence in 1990 was 15.9% in boys and 14.1% among girls. Occasional smoking in 1990 occurred among 8.9% of boys and 15.0% of girls. Twelve years after, smoking prevalence increased for daily smoking in boys to 32.9% and among girls to 30.4%. Occasional smoking decreased to 6.3% in boys, and increased to 17.8% among girls. There were no remarkable changes in prevalence from 2002 to 2006. Among adolescents in Croatia, there was high risk for smoking among adolescent population. High smoking rate among pupils of medical schools predicts not only high mortality due to smoking over 20-30 years, but also implicates for bad habit among professional health workers, if no policy interventions were taken. PMID- 22053544 TI - The personality traits and social characteristics of Croatian heroin addicts and cannabis users. AB - The purpose of this study was to investigate differences in social characteristics (level of education, working and family status, and criminal record) between heroin addicts, cannabis users and a control group. Additional goal was to explore the possibility of discerning subjects of different addiction status (of both gender) based on their scores on Eysenck Personality Questionnaire (EPQ). In comparison to the control group, heroin addicts and cannabis users had lower level of education, were more frequently unemployed and with criminal record, and more often came from dysfunctional families. In cannabis users the frequency of these characteristics was generally lower than in heroin addicts. Proportion of correct classification of subjects in groups of different addiction status based on the EPQ scores was 23.3% for males (higher than by chance alone), and 30% for females. PMID- 22053545 TI - Influence of depression and somatization on acute and chronic orofacial pain in patients with single or multiple TMD diagnoses. AB - To examine whether psychological variables such as depression and non-specific physical symptoms (somatization) influence pain entity among acute and chronic TMD patients with one or more TMD diagnoses (muscle disorders, MD; disc displacements, DD; and arthralgia, arthritis, arthrosis, AAA). One hundred and fifty-four patients (37 male and 117 female; mean age, 39.0 +/- 14.5 years) with Research Diagnostic Criteria for Temporomandibular Disorders (RDC/ TMD) protocol were selected. Differences in mean depression and somatization scores between acute and chronic TMD patients, as well as TMD patients with one or multiple TMD diagnoses were compared by using the parametric T-test for independent samples. The majority of patients were acute TMD patients (81.8%), while the remaining 28 patients (18.2%) were chronic TMD patients. 62% of patients had only one TMD diagnosis (MD or DD or AAA), 31% of patients had two diagnoses (MD+DD, MD+AAA, DD+AAA) and, finally, 7% of patients had three diagnoses (MD+DD+AAA) according to the RDC/TMD protocol. According to the SCL-90 psychometric evaluation, 19.5% of patients presented a severe depression score (> 1.105), 27.3% of participants presented a severe somatization score with pain items included (> 1.000). The results of the t-test for independent samples showed statistically significant differences between acute and chronic TMD patients (p < 0.001), as well as between patients who were assigned one diagnosis (p = 0.019) and patients who had two or more diagnoses (p < 0.001); for mean levels of depression and somatization scores. Chronic TMD patients and patients with multiple TMD diagnoses had higher rates of depression and somatization in this study. These results could be used in a tailored strategy of TMD treatment. PMID- 22053546 TI - Platelet serotonin concentration at term pregnancy and after birth: physiologic values for Croatian population. AB - The aim of this study was to determine physiological value of platelet serotonin (5-HT) and its variations in the group of women in term pregnancy and after birth. Obtained results were compared to the platelet 5-HT level in nonpregnant women group. Determination of normal level of 5-HT in pregnancy and after could help in its further measurement and evaluation of different psychologic and psychiatric disorders related to pregnant and postpartal period, including better understanding of mood changes after the birth. A total of 137 healthy Croatian women were enrolled in the study--82 of them were pregnant and 55 were not. Their blood was sampled and the platelet serotonin concentration was determined. In pregnant women the blood was sampled twice: at term pregnancy, and soon after birth. The mean value of 5-HT in pregnant women was 1.209 nmol/mg protein, after the delivery 1.045 nmol/mg protein, and in non pregnant 1.088 nmol/ mg protein. The concentrations were significantly different in those three groups. We did not find differences in 5-HT levels in groups divided by age. PMID- 22053547 TI - The possibility of respiratory distress syndrome prevention of premature born children. AB - Pregnant women and premature born children were classified into four groups. In each group there were thirty of them. The first group included the pregnant women with premature rupture of membranes and amniotic fluid effluxed for 72 hours before the delivery. The second group included the pregnant women with amniotic fluid effluxing less then 72 hours before the delivery. The third group included the pregnant women who were given corticosteroids. The forth group was a control group formed by those pregnant women (and their premature born children) whose amniotic fluid did not efflux long and those who weren't given corticosteroids during pregnancy. In all groups of pregnant women we observed: median age of pregnant women, the duration of pregnancy and mode of delivery (vaginal or cesarean section). In groups of premature born children we also observed: newborn birth weight, Apgar score in the first minute after delivery, Apgar score in the fifth minute after delivery, pH of the blood of umbilical cord, L/S ratio of amniotic fluid (lecithin-sphingomyelin ratio), RDS (neonatologist valuation in any degree of RDS developed et newborn child). Symptoms of RDS include tachypnoea, chest wall retraction and cyanosis and a zground glass' appearance of the chest on X-ray. Histopatological examinations of placentas compared the frequency of inflammatory or noninflammatory changes, also in all groups. No significant difference was found among groups of pregnant women for the following factors: the age of pregnant women, the duration of pregnancy and mode of delivery. No significant difference was found among the groups of children for the following factors: newborn birth weight, Apgar score in the fifth minute after delivery, blood pH of umbilical cord, L/S ratio of amniotic fluid. Significant difference was found among groups for the following factors: Apgar score in the first minute after delivery, the frequency of RDS and hystology of placentas. The prevention of premature delivery is the most important. All the pregnant women with symptoms of the premature delivery must be transported to the centers with the well developed unites of intensive neonatal care ("transport in utero"). PMID- 22053548 TI - The application of autogenic training in counseling center for mother and child in order to promote breastfeeding. AB - The aim of this study was to investigate whether mothers with newborn children, the usage of autogenic training with advice on breastfeeding effect on: the decision and the duration of breastfeeding, increase maternal confidence and support. It was assumed that the above result in a higher percentage of mothers who exclusively breastfed baby during the first six months of child's life. The survey was conducted in the Association "For a healthy and happy childhood" Counseling center for mother and child, in Bjelovar in 2010. The Counseling center was attended by 100 nursing mothers with children aged up to two months. They randomly went to the study or control group. Mothers of both groups were advised to successful breastfeeding. Study group has practiced autogenic training until the child's age of six months. In parallel, by using psychotherapeutic interview and specific questionnaires we collected data on the somatic, psychological and social situation of the mother, discovered mother's mental changes (anxiety, depression) that were treated. The results at the end of the study confirm the initial expected benefits from the application of autogenic training. Mothers of the study group were significantly more emotionally balanced with a higher self-esteem. Autogenous training with the advices for successful breastfeeding conducted in this counseling center contributed in significantly higher rate of breastfeeding children up to six months of life, improved mental and physical health of mother and child and their peculiar relationship. PMID- 22053549 TI - Ultrasonographic assessment of kidney dimensions in first six months of life. AB - The kidney growth in children is not linear. The aim of this study was to define normal dimensions of kidneys in healthy infants during the first six months of life. A prospective ultrasonographic screening of 1870 kidneys in 935 healthy full-termed infants (476 males, 459 females) was done throughout a 5-year period. Measured kidneys were divided into six age groups according to gender and side. In the first three months of life males had both kidneys longer than same-age females (p < 0.05). In the next three-month-period the difference between sexes was not significant (p > 0.05). Left kidneys were longer than right kidneys in both sexes in the first six months of life (p < 0.01). Four nomograms with normal values of kidney lengths, according to age, sex and side were done in newborns and infants in the first 6-months of life. PMID- 22053550 TI - Relationships between anthropometric, body composition and bone mineral parameters in 7-8-year-old rhythmic gymnasts compared with controls. AB - The aim of the study was to investigate the relationships between specific anthropometric (9 skinfolds, 13 girths, 8 lengths and 8 breadths), body composition (body fat %, fat free mass [FFM], fat mass [FM]) parameters and bone mineral parameters (bone mineral density [BMD], bone mineral content [BMC) in young rhythmic gymnasts and same age controls. Eighty nine 7-8-year-old girls participated in this study and were divided to the rhythmic gymnast's (n = 46) and control (n = 43) groups. Body composition was determined by dual energy X-ray absorptiometry (FFM, FM, body fat %, BMD and BMC). Body fat % and FM were lower and BMD and BMC values at lumbar spine (L2-L4) and femoral neck were higher in rhythmic gymnasts compared with controls. All measured skinfold thicknesses were thicker in controls. In girths, lengths and widths there were only few significant differences between the groups. Stepwise multiple regression analysis indicated that skinfold thicknesses (supraspinale and medial calf) influenced L2 L4 BMD only in controls 38.2% (R2x100). Supraspinale and iliac crest skinfold thicknesses characterised L2-L4 BMC 43.9% (R2x100). Calf girths influenced BMD in L2-L4 52.3% (R2x100) in controls. BMC in L2-L4 was dependent only on mid-thigh girths 35.9% (R2x100). BMD in L2-L4 was dependent on tibiale-laterale height 30.0% (R2x100). Biiliocristal breadths together with sitting height characterised BMC in L2-L4 BMD 62.3% (R2x100). In conclusion, we found that the relationships between anthropometry, body composition and bone parameters in young rhythmic gymnasts are weak. In control group first of all lower body anthropometric parameters significantly correlated with BMD and BMC in spine. PMID- 22053551 TI - Types of body posture and their characteristics in boys 10 to 13 years of age. AB - The main goal of the study was to determine the types of body posture of boys (n = 273), 10 to 13 years of age, by means of the body posture assessment method based on the software Posture Image Analyzer. The results should enable better understanding of postural issues, as well as timely and more precise selection of kinesitherapeutic procedures. Values of 5 front view and 4 sagittal view indicators of standing body posture were measured by means of subjects' photographs and software Image Posture Analyzer Cluster analysis (K-means method) revealed three types of body posture in both the anterior and sagittal plane. Their characteristics were determined with discriminant analysis. In sagittal indicators three posture types are recognizable: (a) correct sagittal body posture (29.3%), (b) mild impaired sagittal body posture (41.8%), (c) marked impaired sagittal body posture (28.9%). In anterior indicators also three posture types are recognizable: (a) correct anterior body posture (19.4%), (b) mild scoliotic body posture in the lumbar region (47.6%), (c) mild scoliotic body posture with double curvature (33%). PMID- 22053552 TI - Vagus nerve stimulation in the treatment of patients with pharmacoresistant epilepsy: our experiences. AB - Vagus nerve stimulation (VNS) for the treatment of refractory partial epileptic seizures with or without secondary generalisation in patients older than 12 years was approved in Europe in 1994 and in the United States in 1997. We have studied the efficacy of VNS in patients with pharmacoresistant epilepsy hospitalized in the Neurology Department of the University Hospital Centre Zagreb. From 1997 to 2001 we have implanted VNS in 11 patients with pharmacoresistant epilepsy, who were magnetic resonance imaging (MRI) negative and from May 2007 to May 2009 in 11 patients with pharmacoresistant epilepsy, 9 of them were MRI positive, and were inoperable due to localisation of the pathomorphologic changes (ganglioglioma, hamartoma, various types of cortical dysplasia, porencephalic cysts), 2 were MR negative. In the group of MRI negative patients 1 patient had complex partial seizures (CPS), 6 patients had CPS with secondary generalisation, 2 patients had primary generalized epilepsy (PGE) including myoclonic, absence, atonic and tonic-clonic seizures, one patient had PGE and CPS, and 3 patients had Lennox-Gastaut syndrome (LGS). In the group of MRI positive patients one patient had elementary partial seizures (EPS) and CPS, two patients had EPS and CPS with secondary generalisation, one patient had CPS, 3 patients had CPS with secondary generalisation, and 2 patients had CPS with secondary generalisation as well as atonic seizures. After continuous follow-up of 11 MRI negative patients during 5 years and 2 MRI negative patients during one year there was decrease in mean seizure frequency of 51.67%. After continuous follow-up of 9 MRI positive patients during 2 years there was decrease in mean-seizure frequency of 61.9%. The most frequent side effects were hoarseness, throat pain and cough in the "on phase" of the VNS, but they were mild and transitory. We can conclude that VNS was effective mode of therapy in our group of patients with pharmacoresistant epilepsy. PMID- 22053553 TI - Dental health and dental care in children with cerebral palsy. AB - The aim of this study was to determine a difference between children with cerebral palsy (CP) and healthy children, regarding health condition of teeth and oral tissuses. Disfunction of masticatory system, in children with CP, causes many problems with mastication. Nonfunctional mastication is related with the consumption of mushy food and decreased selfcleaning of occlusal and aproximal surfaces. All that leads to higher incidence of dental caries. Comparing the DMTF/dft (decayed, missing, filled tooth) index, it is evident that there is no statistically significant difference in a tooth morbidity between the group of healthy children and group of children with CP. The healthy children have statistically significant more teeth with fillings with respect to children with CP. Extractions are more common in children with CP. There is no statistically significant difference between those two groups regarding decayed teeth, one of components of DMFT index. Decayed components are more common than the extractions and fillings in both groups, which shows the insufficient curative care for all children in both groups. It can be concluded that there is a certain need of early beginning and a better organization of the preventive pediatric and dental care, in order to decrease the appearence of dental decay and increase the level of dental health, in this challenged population. PMID- 22053554 TI - Cancer and cardiovascular diseases nutrition knowledge and dietary intake of medical students. AB - The aims of this study were to determine medical students' knowledge regarding the association between dietary factors and the risk of cancer and cardiovascular diseases and to investigate if this knowledge has an impact on their dietary intakes. Three hundred and ninety medical students (males and females) were included in a study and grouped according to their daily fibre and fat intakes. For diet-disease knowledge, questions from the General Nutrition Knowledge Questionnaire for Adults were used and dietary assessment was done with Food Frequency Questionnaire. The obtained results showed that the students' diet disease knowledge was generally inadequate. Higher level of diet-disease knowledge was among those with high dietary fibre intake, with slightly better scores for dietary factors and risk for cardiovascular diseases than the risk for cancer. Better diet-disease knowledge positively correlated with higher intake of fish (p = 0.027, p = 0.001) and vegetables (p = 0.019, p = 0.001) in high fibre groups of both gender, and in females additionally with fruit intake (p = 0.038, p = 0.007). A higher dietary fibre intake among studied students seems to be a factor that ensures lower obesity rates, lower intake of energy and lower consumption of coffee, sweets and alcoholic drinks. On the basis of the results of this study, it is clear that medical schools should provide in their nutrition programs the opportunity for students to learn about their own dietary and lifestyle behaviours, in order to more knowledgably and convincingly counsel their future patients. PMID- 22053555 TI - Prediction of ovarian tumor malignancy. AB - Ovarian cancer is the leading cause of mortality among gynecological cancers. The aim of the study was to form the decision rules for distinguishing benign from malignant ovary lesions. The research was conducted on 201 women with ovary tumor. Commonly used specific markers for ovarian cancer (biochemical marker Ca 125, ultrasound and vascular markers) were used. The significant difference in the presence of an ultrasound and vascular markers between benign and malignant ovary changes along with the significantly different level of Ca 125 is confirmed. To a specific marker certain score number was appointed and the scoring system was formed. The incidence of benign/malignant ovary changes was observed in the researched group regarding anthropometric parameters (age, marital and menopausal status and number of deliveries). There is also significant difference in the incidence of benign/malignant ovary tumor regarding these parameters. Based on combination of the scoring system and anthropometric parameters the decision rules for distinguishing benign from malignant ovary tumors were formed. The logistic regression method was used. We proved that this method has higher accuracy in prediction of malignancy in women with ovary tumors than using morphological, Doppler or anthropometric parameters separately. PMID- 22053556 TI - Helicobacter pylori infection and acute myocardial infarction. AB - The aim of this investigation was to determine whether H. pylori infection is an independent risk factor for acute myocardial infarction (AMI), determine is there a link between H. pylori infection and severity of disease. In this prospective, single centre study, were enrolled 100 patients with AMI and control group was consisted 93 healthy individuals. The results of this study showed no difference between H. pylori seropositivity distribution in the investigate and control group (29 vs. 26 %) and there was no significant difference on the severity of the disease. There was significant association in the patients with three and more risk factors, where the patients with lower blood pressure (124.4/77.4 vs. 145.9/87.7 mmHg) and better controlled diabetes (HbA1c 6.1% vs. 6.9%) had greater risk for AMI if they are H. pylori seropositive. The large multicentric trials would be needed to define a precise role of H. pylori infection on the developement of AMI. PMID- 22053557 TI - Low adiponectin serum level--reduced protective effect on the left ventricular wall thickness. AB - Adiponectin, secreted by fat tissue, is down - regulated in obesity and may be involved in obesity-related disorders. It has anti-inflammatory, antiatherosclerotic and antidiabetic effect. Obesity is a strong predictor for hypertension and cardiovascular diseases. Recent studies showed that adiponectin level has important role in metabolic disorders, arterial hypertension and ischemic heart disease but its effect on left ventricular hypertrophy (LVH) has not been fully clarified. The aim of this research is to determine whether the protective effect of adiponectin against development of left ventricular hypertrophy is decreased in hypertensive overweight patients. The study included 61 adult, overweight hypertensive patients, with body mass index in range 25-30 kg/m2. Patients had regular morning glucose serum values and regular creatinine level. They were divided into four groups, according to sex and the presence of LVH. There were 16 female and 15 male hypertensive patients with LVH and 15 female and 15 male hypertensive patients without LVH, who were a control group. Glucose profile, lipidogram, creatinine clearance and anthropometric measures were determined in all patients. Cardiovascular measurements were taken applying two-dimensional ultrasound. Adiponectin serum level was measured using enzyme immunoassay (ELISA). Results showed that adiponectin serum level was significantly lower in hypertensive, overweight females and males with LVH than in the control groups without LVH. Adiponectin serum level did not correlate significant with intraventricular or with posterior wall thickness of left ventricle. Hypoadiponectinemia presents part of neurohumoral, non-haemodynamic system who contributes to obesity-related hypertension and left ventricular hypertrophy development. Low adiponectin level together with others adipokines, cytokines and chemokines secreted by fat tissue could contribute to pathophysiologic changes of the myocardium via unknown molecular mechanisms yet. PMID- 22053558 TI - Arrhythmogenic right ventricular dysplasia and sudden cardiac death in Croatians' young athletes in 25 years. AB - The paper deals with the sudden cardiac death during training in male athletes in Croatia. The data are a part of a retrospective study dealing with 67 sudden death due to physical activity in men in Croatia during 25 years: from January 1, 1986 to December 31, 2010. Two of them suddenly died during training due to malignant ventricular arrhythmia because of the arrhythmogenic right ventricular dysplasia. First was a short trails runner aged 24, with no any previous physical discomforts, who suddenly collapsed and died during training. The second was a soccer player aged 13, with no any previous physical discomfort, who suddenly collapsed and died during training. A sudden cardiac death due to physical exercise in young athletes in Croatia suffered of arrhythmogenic right ventricular dysplasia reached 0.07/ 100.000 yearly (p = 0.00000), in all young athletes suffered of heart diseases reached 0.19/100 000 (p = 0.00005), and in the total male population aged 15-40 engaged in sports and recreational physical exercise: 0.71/100.0000 (p = 0.00001). PMID- 22053559 TI - Influence of in-hospital cardiac rehabilitation on psychological status after myocardial infarction in patients with D-type personality. AB - The aim of this study was to determine the number of D-type personality patients in the group with a history of myocardial infarction (MI) and the influence of comprehensive in-hospital cardiac rehabilitation (iCR) on their psychological status (PS). The study included 316 consecutive patients aged 18 to 65 with MI in the last six months admitted into the programme of iCR. Surgical revascularized patients, clinically unstable patients and patients with sever chronic diseases and disorders were excluded. At the beginning and in the end of iCR diagnostic exam, hematological/biochemical blood analysis, ergometric testing was conducted. At the beginning and four weeks after the finish of the iCR estimation of PS was conducted. Distress scale 14 (DS14) questioner was used for that purpose. In the period of three weeks, patients were included in the programme of comprehensive iCR. Out of 316 patients in the study group 83.2% were male, while 16.8% were female. Average age of the patient was 51.3 +/- 7.2. When being admitted to iCR 42.7% patients had characteristics of D-type personality. Those patients had substantially lower level of body mass and body mass index. In the same time there were no differences among groups in risk factors, values of clinical, laboratory and diagnostic parameters. During iCR study group had more complications in comparison to the control group. At the end of iCR substantial rise of functional capacity of patients, improvement of lipid profile and lowering of glycaemia was recorded. Also at the end of iCR antiarrhythmics and psychopharmaceutical medicaments were more often prescribed to the patients in the study group. Four weeks after the iCR share of D-type personality patients was 41% and 71% of study group patients kept their D-type structure. PMID- 22053560 TI - Defense mechanisms in alcohol dependent patients with oral and oropharinegal cancer. AB - The effects of psychological factors in alcoholics with malignant tumor of the oral cavity and oropharynx are scarcely explored. The aim of the research was to examine early family relations and investigate differences in the use of defense mechanisms in alcohol dependent patients suffering from malignant tumor of the oral cavity and oropharynx compared to alcohol dependent persons without malignant tumors and healthy controls. The research included 51 alcohol dependent patients treated for malignant tumor of the oral cavity and oropharynx at the University Hospital Center Rijeka from 2005 to 2009. The control groups corresponded to the experimental group in age, sex and education level. The research used a general demographic questionnaire, the Mini International Neuropsychiatric Interview and the Revised Questionnaire of Life Style and Defense Mechanisms. The research groups showed significant differences in difficult childhood (p < 0.001) including abuse (p = 0.004). The alcohol dependent persons suffering from malignant tumors of the oral cavity and oropharynx significantly less frequently used primitive defense mechanisms of regression (p = 0.004) and displacement (p = 0.013) compared to alcoholics without malignant tumors who significantly more often used neurotic defense mechanisms - compensation (p = 0.005) and intellectualization (p < 0.001). The earliest emotional experiences and quality of family relations affect the development of defense mechanisms. These are the psychological factors in the development of oropharyngeal cancer in alcohol addicts. PMID- 22053561 TI - Prohypertensive effects of non-steroidal anti-inflammatory drugs are mostly due to vasoconstriction. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) have prohypertensive effects and blunt the effects of many antihypertensives. The mechanism of this interaction is still not understood enough. The objective of this investigation was to determine the level of prohypertensive effects of two NSAIDs (ibuprofen, piroxicam) and paracetamol, co-prescribed with two antihypertensive drugs (lisinopril + hydrochlorothiazide, amlodipine), and to improve the understanding of this interaction. A prospective clinical trial, conducted in a Croatian family practice, included 110 already treated hypertensive patients, aged 56-85 years; 50 control patients and 60 patients who were also taking NSAIDs for osteoarthritis treatment. The antihypertensive regimens remained the same during this study, while NSAIDs and paracetamol were crossed-over in three monthly periods. Blood pressure, body weight, serum creatinine, potassium, sodium, diuresis and 24 h urinary sodium excretion were followed-up. In the lisinopril/hydrochlorothiazide subgroup, both ibuprofen and piroxicam elevated mean arterial pressure by 8.9-9.5% (p < 0.001). Body weight increased significantly in the lisinopril/ hydrochlorothiazide + piroxicam subgroup only, while creatinine, urinary output and electrolyte values did not change appreciably in any of the subgroups. NSAID's prohypertensive effects seem to be mostly due to vasoconstriction and, to a minor degree, to volume expansion, since no marked changes in body weight, urinary output, serum creatinine or serum/urinary electrolyte profile were observed. PMID- 22053562 TI - Drug related deaths in the Split-Dalmatia County 1997-2007. AB - Drug overdoses are a major cause of mortality for drug users and, in many countries, are the leading cause of death in this group. The aim of the present study is to explore the frequency of all drug related deaths in the Split Dalmatia County in the period between 1997 and 2007 and to analyze some of the characteristics of these deaths to help target preventive policies. The data on drug related deaths were collected using records from the Department of Forensic Medicine, Clinical Hospital Centre Split, University of Split, School of Medicine. There were 190 drug related deaths in the observed period of 11 years. Statistically significant difference (p = 0.004, chi2-test for trend) was found in the number of deaths in 1997 in comparison with the number of deaths in 2007. The majority of 105 (55%) the decedents were 25-34 years old, and 92.1% (175) of them were male. There was a 94% higher probability of mortality in the 25-34 years group (chi2 = 5.55, p = 0.064). Average age of all dead people was 31.01 +/ 7.59 years (median 31.0 years; range 18-49). Almost three quarters of the decedents were single and more than three fifths hadn't been employed. The most common location of death was at home. Approximately, 80% were autopsied followed by full histological and toxicological analyses. Out of all examined cases, the majority of drug related deaths (93 or 60.8%) were attributed to heroin. Heroin was the sole cause of death in 35 (22.9%) cases. Methadone was cause of death in 24 (15.7%) cases. 3.4-methylenedioxy-methamphetamine (MDMA) deaths were rare (3.3%). Cocaine deaths were also rare (1.3%). Three fifths (55.6%) of the cases involved includes multi-substance use. During the investigation there was an evident trend towards multi-substance abuse patterns. These data suggest that interventions to prevent drug related mortality should address the use of drugs such as heroin and alcohol in combination. PMID- 22053563 TI - Obesity in type 2 diabetes: prevalence, treatment trends and dilemmas. AB - This retrospective observational study investigated the prevalence of obesity in persons with type 2 diabetes, trends in obesity resulting from the duration and treatment of diabetes, and treatment-related changes in HbA1c and body mass index (BMI). Data on 1773 type 2 diabetics (802 men and 971 women) were obtained from the CroDiabNET registry. Follow-up included the analysis of patients' age, disease duration, diabetes treatment, BMI and HbA1c values. A significantly higher rate of overweight and obesity was found in persons with type 2 diabetes as compared to the general population. A significant decrease in BMI was observed in the groups treated by diet, and in those treated by oral hypoglycaemic agents (p < 0.05), regardless of their pharmacotherapeutic group, in contrast to a significant increase in BMI observed in the groups treated with insulin (alone or in combination with oral hypoglycaemic agents) (p < 0.05). Persons with type 2 diabetes lost weight only during the first years of the disease, while with diabetes duration and insulin treatment they regained weight. A significant increase in HbA1c was observed in the groups treated with sulfonylureas (p < 0.05), whereas all other groups revealed either a significant decrease (p < 0.05) or no change in HbA1c. Our findings suggest the necessity of an integrated approach to managing type 2 diabetic patients that would simultaneously address both diabetes and obesity. Good glycaemic control is imperative and diabetes treatment should not be postponed. Because of a possible concomitant weight gain, aggressive weight control measures should be applied concurrently in order to achieve maximum treatment benefit. PMID- 22053564 TI - The role of oxidative stress after retinal laser photocoagulation in nonproliferative diabetic retinopathy. AB - Diabetic retinopathy (DR) represents the most common chronic complication of diabetes, and it is the leading cause of new cases of blindness in patients between 20-74 years old in developed countries. Laser photocoagulation (LF) represents an efficacious approach to the treatment of DR. Oxidative factors, such as free radicals (FR), are continuously generated in aerobic organisms as a result of different metabolic processes. It is well known that oxidative stress plays a role in the development of DR. The aim of this study was to evaluate the thermal effects of the scatter retinal laser photocoagulation technique on the production of FR. A total of 90 patients were enrolled in this study. They were divided in 3 groups: 30 diabetic patients with DR, 30 diabetic patients without DR, and 30 control individuals without diabetes mellitus (DM). Full scatter retinal LF was performed in all patients with DR. We measured the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GPOD), catalase, and total antioxidative status (TAS). Of the 30 DR patients, 13 showed the appearance or worsening of macular edema after LEF, whereas the other 17 patients showed no change. Thirty days after LF, improvement in visual acuity was observed, but this change was not statistically significant. The mean plasma or erythrocyte lysate concentrations of various antioxidants were significantly lower in the diabetic patients without DR compared to the individuals without DM and in the diabetic patients with DR compared to the individuals without DM; the diabetic patients with DR did not show lower concentrations of the antioxidants compared to the diabetic patients without DR. The concentrations of SOD, GPOD, catalase, and TAS were significantly lower in the diabetic patients with DR after retinal scatter LF, which could be the consequence of retinal oxidative stress caused by the LF thermal effect. PMID- 22053565 TI - Intravitreal Bevacizumab with or without triamcinolone for refractory diabetic macular oedema. AB - We evaluate the effect of intravitreal injections of Bevacizumab (IVB) alone or combined with triamcinolone (IVT) in the first injection for treatment of refractory diabetic macular oedema (DME). Sixty eyes of sixty patients with refractory DME were included. Half of them received injections of IVB (1.25 mg/0.05 ml) or combined IVB and IVT (1.25 mg/0.05 ml and 2 mg/0.05 ml respectively). The primary outcome measure was change in central macular thickness (CMT). Secondary outcome measures were change in best-corrected logMAR visual acuity (BCVA) and incidence of potential adverse events. Central macular thickness was reduced significantly in both the IVB and IVB/IVT groups. At week 24, CMT change compared to the baseline was -93.7 microm (95% CI, -172.2 to 19.26) in the IVB group and -93.1 microm (95% CI, -154.4 to -29.7) in the IVB/IVT group. There was not a significant difference between the IVB and the IVB/IVT groups. Improvement of BCVA was initiated at weeks 6 and 12 in the IVB/IVT and IVB groups respectively. Anterior chamber reaction was noticed in six (20%) and six (20%) eyes respectively in the IVB and IVB/IVT groups the day after injection, and it resolved with no sequel. Elevation of intraocular pressure (IOP) occurred in two eyes (6%) in the IVB/IVT group. Intravitreal injections of Bevacizumab had a beneficial effect on refractory DME in terms of CMT reduction and BCVA improvement. Addition of triamcinolone in the injection seemed to induce earlier visual improvement; however, it did not show any significant additive effect later during follow-up. PMID- 22053567 TI - Risk behaviors for getting HIV infection among the Croatian men who have sex with men in 2007. AB - This survey was conducted with the aim of obtaining the information on the sexual risk behavior of Croatian men who have sex with men (MSM) two years after the first research. There was total of 820 respondents recruited at seven frequent meeting places of Croatian MSM in Zagreb and Rijeka, as well as one gay-oriented web-site. The overall response rate was 17.6% which is 1.4 percentage point less than it was two years ago. The rate of condom use during last anal intercourse was 53.2% and 69% of those who used a lubricant had chosen a correct water-based product which is increase of 15% comparing to the last research. Only 27% of those who had also had sex with women (MSM/MSW) during last 12 months regularly used protection. The results of this research suggest that there are trends in declining of some risk behaviors among Croatian MSM but there is a lot of space for focused and effective prevention activities on increasing the risk perception and reducing risk behaviors. PMID- 22053566 TI - Epidemiologic characteristics of human campylobacteriosis in the County Primorsko goranska (Croatia), 2003-2007. AB - The aim of the study was to investigate campylobacteriosis incidence in the County Primorsko-goranska (Croatia) between 2003 and 2007 and to find out possible connection with environmental factors (the average monthly temperature and total monthly precipitation). The data (number of stool samples examined, age and sex distribution of patients, monthly distribution of isolates and distribution of isolates according to the species) from the Laboratory for Diagnostics of Enteric Infections of the Teaching Institute of Public Health of the County Primorsko-goranska (Croatia) were analyzed retrospectively. During the observed period 30,164 stool samples were examined for Campylobacter spp. Campylobacters were identified in 1,242 (4.12%) samples. The overall annual campylobacter incidence rate was 81.3 +/- 21.9/100,000 population. Campylobacter jejuni was found in 1,093 (88%) and C. coli in 149 (12%) patients. Our findings showed age distribution of patients typical for developed countries. The patients were mostly children under 5 years (484.4 +/- 129.1/ 100,000, p < 0.001) and between 5 and 9 years of age (226.5 +/- 60.5/100,000, p < 0.05). Male consistently experienced higher rates, but the difference between genders was significant in the age groups from birth till late twentieth (p < 0.001). Campylobacter rates were significantly associated with monthly average temperatures (p < 0.05), but not with precipitation. Further investigations into the incidence of campylobacteriosis on the national level are necessary. The causes of the noticed monthly distribution, sources of infection and connection with the routes of transmission in humans need to be elucidated as well. PMID- 22053568 TI - Croatia: still a low-level HIV epidemic?--seroprevalence study. AB - Central Europe is a region with a low prevalence of infection with human immunodeficiency virus (HIV). Until the end of 2007, 663 HIV cases were recorded in Croatia, almost exclusively among most at-risk populations. The aim of this research was to determine the HIV prevalence among most at-risk populations and the level of the HIV epidemic in Croatia. According to the World Health Organization classification there are three levels of HIV epidemics: generalized (prevalence in general population > 1%), concentrated (prevalence in general population < 1% and prevalence in at least one of the most at-risk populations > 5%) and low-level epidemic (prevalence in general population < 1% and prevalence in each most at-risk population < 5%). This was a research with convenience samples of most at-risk populations. The respondents were recruited by their peers, all non-governmental organizations that provide services for most at-risk populations and the researchers. Sera were tested using the fourth generation enzyme-linked fluorescent assay (EIA test) and reactive test were confirmed using the Western Blot test. In this research, the highest HIV prevalence was found within the men who have sex with men group (7/232 = 3%, 95% CI = 1.3-6.3%) and commercial sex workers (1/70 = 1.4%, 95% CI = 1-7.8%). In these samples we were unable to determine whether Croatia is facing a low-level epidemic due to the fact that the prevalences were not statistically significantly lower than 5% (p = 0.115 and p = 0.1, respectively). For the remaining samples the prevalence was statistically significantly lower than 5%, which points to a low-level epidemic. The prevalences in these samples were 7/593 = 1.2% (95% CI = 0.5-2.4%) in people with more than two sexual partners within the last 12 months, 2/249 = 0.8% (95% CI = 0-2.9%) in people with sexually transmitted infections in history, 2/317 = 0.6% (95% CI = 0-2.2%) in clients of sexual workers, 2/323 = 0.6% (95% CI = 0 2.2%) in injecting drug users and 0.2% (95% CI = 0-1%) in the sample of migrant workers. Based on the results of this survey, Croatia would be classified as having a low-level HIV epidemic although the confidence limits in two most-at risk groups, men who have sex with men and commercial sex workers, overlap 5%. PMID- 22053569 TI - Complications after hip rearthroplastics with revision endoprosthesis. AB - The stability of the revision endoprosthesis components is more difficult to achieve than in primary endoprosthesis due to large bone defects and/or decreased bone mass quality. That is the reason for more frequent complications for revision than in primary arthroplasty. The aim of this study was to investigate the frequency of complications in 122 patients who were operated with the revision endoprosthesis in the Department of Orthopedics in University Hospital Split in the period of 1998 to 2007 and accepted to participate in this study. There were 3 patients treated on bought hips. The average follow up time was four years (0.6-10.6). There were 32 (26.2%) males and 90 (73.8%) females. The average age was 70.66 +/- 7.63 years. The average time from operation to physical therapy was 3.53 +/- 2.56 days. There were 27 (21.6%) complications. The most common complication was infection in 9 (7.2%) cases. From those cases, 4 (3.2%) had superficial, and 5 (4%) had deep infection. From other complications, there were 5 (4%) endoprosthesis reluxations, 2 (1.6%) periprosthetic femur fractures, 5 (4%) urinary infections, and 6 (4.8%) other complications (lung mycroembolia, heart infarction, lumbal plexus lesion from L2, spinal cord infarction with paraplegia, pneumonia and severe sacral bed-sore). There were 10 (8%) re interventions following the revision arthroplasty. The result was good or excellent in 80% of operated patients, satisfied in 17%, and bad in 3%. The revision hip procedures are characterized with a high complications incidence rate. Our results are comparable with the results from literature. PMID- 22053570 TI - Nail position has an influence on anterior knee pain after tibial intramedullary nailing. AB - Our aim was to determine the possible relationship between anterior knee pain (AKP) and nail position marked as a distance from tip of nail to tibial plateau (NP) and to the tuberositas tibiae (NT). Nail position has an influence on anterior knee pain after tibial intramedullary nailing. We evaluated postoperative outcome results of 50 patients in the last 3 years with healed fractures initially treated with intramedullary (IM) reamed nails with 2 or 3 interlocking screws on both parts of the nail and with the use of medial paratendinous incision for nail entry portal. Patients marked a point on the visual analog scale (VAS) that corresponded to the level of postoperative AKP felt. Two groups of patients were formed on the basis of AKP (pain level was neglected): groups A and B, with and without pain, respectively. The difference between the two groups concerning NP measurements was statistically significant (p < 0.05), but not concerning NT measurements at the p < 0.05 level. Patients were classified by pain with high accuracy (98%) according to a classification tree. Symptoms of AKP did not appear if the tip of the nail position was more than 6.0 mm from the NP and more than 2.6 mm from the NT. However, for better evaluation of these results it will be necessary to examine a larger number of postoperative patients with AKP. PMID- 22053571 TI - Surface roughness of one nanofill and one silorane composite after polishing. AB - The aim of this study was to compare the roughness of the surface of one nanofill (Filtek Supreme XT 3M Espe, St. Paul, USA) and one silorane (Filtek Silorane, 3M Espe, St. Paul, USA) composite after polishing. Five specimens of each composite were polymerized under a polyester strip for 40 seconds. After curing four probes were polished with different Sof-Lex discs and one probe with Pogo for ten seconds. For the surface appointment a contact stylus profilometer was used. The profilometer made ten tracings for each sample at different locations. There was a significant difference in roughness between both composites. The Ra (average surface roughness) results for the silorane composite were almost always significantly higher than for the nanofill composite (T-test). For both composites Sof-Lex fine and superfine discs produced smoother final surfaces than Pogo. The nanofill composite used showed the smoothest surfaces after the polishing and finishing procedures. PMID- 22053572 TI - Distribution of RoekoSeal sealer applied by three obturation techniques. AB - The aim of the study was to evaluate the distribution of Roekoseal Automix sealer using three different obturation techniques. Forty-five single-rooted extracted human teeth were prepared in a crown-down manner using ProFile instruments. After instrumentation the specimens were filled using Roekoseal Automix with the cold lateral condensation, Thermafil and Obtura II techniques. Each root was sectioned horizontally. Color images were obtained using a reflected-light microscope. The cross-sections were assessed by microscopy for distribution of the sealer. Root canals filled with cold lateral condensation technique had statistically significant (p = 0.0001) more sealer in the apical portion in comparison to the apical portion of the specimens obturated with Thermafil and Obtura II techniques. PMID- 22053573 TI - Effect of nordic walking on functional ability and blood pressure in elderly women. AB - The aim of the study was to analyze the effects produced by the use of experimental program (Nordic polewalking) on functional abilities in elderly women. Three-month polewalking led to reduction in the pulse rate at rest, diastolic and systolic blood pressure at the level of significance of 0.01 (p = 0.000). Polewalking improved the values of fitness index (FITIND) and maximal oxygen consumption (VO2max) at the level of significance of 0.01 (p = 0.000). On final measurement, three variables, i.e. pulse rate at rest - HRR (E = 73.42 vs. C = 79.68), systolic blood pressure - BPS (E = 118.42 vs. C = 123.65) and diastolic blood pressure - BPD (E = 79.04 vs. C = 83.54), showed lower results in experimental group compared with control group. On final measurement, experimental group showed higher values of the FITIND (E = 81.79 vs. C = 62.66) and VO2max (E = 21.83 vs. C = 16.81) variables as compared to control group. Accordingly, such a moderate physical activity, which is not too vigorous yet intensive enough to induce favorable changes, appears to be recommendable for elderly women. The present study included 60 women from the Novi Sad community, mean age 58.5 +/- 6.90 years, mean body mass 70.9 +/- 15.32 kg and mean body height 164.8 +/- 7.24 cm. Study population was divided into two groups of 30 subjects: experimental (E) group and control (C) group. The experimental program was performed three times a week for three months. The Nordic walking program was so designed for the performers to be in the aerobic work zone throughout the exercise. Nordic walking with poles was performed over three months. Study results revealed functional abilities of the study women to have modified during the longitudinal process. PMID- 22053574 TI - Differences in conative characteristics and perceived group cohesion of the basketball players playing in different positions in the team. AB - Identification of differences in individual conative characteristics and in perceived group cohesion of the basketball players playing in different positions in the team could provide guidelines for a better selection of basketball players and better coaching work. The aim of our study was to determine the differences in relation to the positions of guards and forwards/centres, and the four major positions in the team. The final sample of subjects (74 basketball players) is selected from the initial sample of 107 subjects, selected from nine men's senior basketball teams that played in A-1 Croatian men's basketball league championship in 2006/2007. The results showed no statistically significant difference between basketball players who play in different positions in the team, neither in relation to two basic positions in the team (guards as opposed to forwards/centres), nor in relation to the four positions in the team (point guard, shooting guard, small forward, power forward/centre). PMID- 22053575 TI - Comparative analysis of qualitative dermatoglyphic traits of Albanian and Turkish populations living in the area of Dukagjin Valley in Kosovo. AB - Dermatoglyphic prints were collected from 800 inhabitants of Dukagjin valley in Kosovo. The sample consisted of two ethnically different sub-populations who refer themselves as Albanians (N = 400) and Turks (N = 400). Qualitative analysis of prints concerned the frequency of the patterns on fingers (arch, ulnar and radial loop, whorl, accidental whorl) and on palms (Thenar and I, II, III, and IV interdigital area and the hypothenar, main line index, and the axial "t" triradius position). As was expected due to previous study of quantitative dermatoglyphic traits, in the same population the Alba-nians and Turks showed to be significantly different in most explored qualitative dermatoglyphic variables. Found differences indicated that the reproductive isolation between the Albanian and Turkish population in Kosovo is substantial, despite the fact that those two ethnic sub-populations live in the close vicinity through several centuries. PMID- 22053576 TI - Formation of adhesions at surgical meshes in a rat experimental model. AB - Abdominal wall hernias are surgical problem that are easily solved with laparoscopic surgery. The determining factor for the success of the operation is the right choice and use of surgical mesh as the support material. The most common complication of surgical mesh placement is the formation of adhesions. Aim of this paper is to determine whether there is a statistic difference in formation of adhesions between different surgical meshes in lab environment. Wistar rats were used as the experimental model. After the anaesthesia a 1x1 cm defect of the abdominal wall was made, but the skin was left intact. The mesh was placed directly on the internal organs. The experiment considered four different mesh types. After set time periods of one, two or four weeks the animals were sacrificed and the amount of formed adhesions were evaluated based on the modified Diamond scale. Immediately after the first week we found a statistically significant difference in the adhesion occurrence rate between compared materials. The smallest amount of adhesions was caused by polypropylen + polydoksanon mesh, and the most by polypropilen mesh. Polypropylen + polyglactin mesh showed significant reduction of adhesion formation between the tested weeks. We can conclude that polypropylen + polydoxanon meshes are superior for ventral hernia operation, because those defects are in close contact with the internal organs and it is very important to have the smallest amount of adhesions. PMID- 22053577 TI - Application of tomographic methods in the diagnosis of pathological changes of the jaw. AB - The aim of this study was to evaluate the frequency of specific diagnostic methods used for diagnosis of oral pathologies. The sample consisted of 198 patients (98 man and 100 women) with formulated diagnosis, confirmed postoperatively by histopathological verification. In 74.7% of subjects only X ray diagnostic examination was used. Both X-ray and computed tomography (CT) examinations were used in 18.7% of subjects. Magnetic resonance imaging (MRI) wasn't performed in any subject. In 6.6% of subjects neither X-ray nor CT was performed. The study reported on statistically significant differences in the distribution of specific diagnostic methods according to age groups (p = 0.026). Also, there was statistically significant differences in the distribution of diagnostic methods according to diagnostic groups (p = 0.053). In the group of 37 subjects, in whom both X-ray and computed tomography were used, the majority had carcinomas, followed by fractures and inflammatory cysts. PMID- 22053578 TI - Osteolytic skull metastasis with dural involvement from a papillary thyroid carcinoma. AB - Skull metastatic tumors are relatively rare medical entities and originate most often from the lungs, breast or prostate. We report a case of a 76-year-old woman who presented with a bulging, well-circumscribed mass on the right side of the forehead. Neuroimaging of the cranium detected an osteolytic lesion measuring 7 cm in the largest diameter while propagating outwards and intracranially. A thorough medical history revealed that patient had undergone surgery for invasive breast ductal carcinoma and also for a well-differentiated thyroid carcinoma 13 years ago. Considering patients medical history metastatic breast carcinoma was suspected. After a frontal craniotomy the tumour tissue was totally resected. Histological examination revealed metastatic papillary carcinoma characterized by ground-glass nuclei with intranuclear pseudo inclusion and nuclear grooves. We report clinical and neuroradiological features of this uncommon lesion and discussed the differential diagnosis of skull osteolytic lesion together with the treatment management. PMID- 22053579 TI - Microbiological analysis of the mummy of St. Marcian. AB - The paper provides the results of the microbiological analysis of samples taken from the mummified remains of St. Marcian. Microorganisms found belong to bacteria and fungi of the genera Aspergillus, Bacillus, Penicillium, Sarcina, and Shewanella which are all apart of the common air, soil, and human microbial flora and therefore present no health hazard. PMID- 22053580 TI - A boy with Dent-2 disease. AB - Dent-2 disease is an X-linked renal tubulopathy associated with mutations in OCRL gene. It is characterized by low-molecular weight proteinuria, hypercalciuria, nephrolithiasis/nephrocalcinosis and progressive renal failure. Patients may have some extra-renal symptoms of Lowe syndrome, such as peripheral cataracts, mental impairment, stunted growth or elevation of creatine kinase/lactate dehydrogenase. Our patient was suspected to suffer from Dent disease at 8 months of age because of proteinuria and hypercalciuria. He had no prominent extra-renal symptoms. OCRL mutation in exon 1 (c.217_218 del TT p.L73F, fs X1) was found. He was treated with amiloride+hydroclorthiazide and citrate with good results in reducing calciuria. His renal ultrasound, ophthalmologic and cardiologic examinations, mental development and other laboratory findings are normal till date. PMID- 22053581 TI - Chondromyxoid fibroma of the second metacarpal bone--a case report. AB - This report describes a chondromyxoid fibroma of the second metacarpal bone in a 32-year-old female patient. Chondromyxoid fibroma is a rare, benign, slow-growing bone tumor of cartilaginous origin. Tumor has a high recurrance rate. Our aim was to show successful treatment of a metacarpal chondromyxoid fibroma with wide resection and implantation of finger join endoprosthesis. PMID- 22053582 TI - Advantages of intramedullar fixation in treatment of congenital tibial pseudoarthrosis--a case report. AB - This report describes a case of a 29-year old patient with congenital pseudoarthrosis of the distal tibia previously treated unsuccessfully by a conventional surgical method. Tibial congenital pseudoarthrosis is a rare disease characterized by segmental osseous weakness resulting in deformation of the bone and spontaneous fractures which progresses to a tibial nonunion. In our case we used intramedullary stabilization with bone grafting and six month after operation congenital pseudarthrosis of the tibia healed. PMID- 22053583 TI - Retroperitoneal and metachronous testicular germ cell tumors with different histology and teratoma growing syndrome--a case report. AB - It is presented a case of a 32-year-old male with the three primary tumors diagnosed within a time period of 3 years; retroperitoneal nonseminoma in 2002, retroperitoneal mature teratoma in 2004, and metachronous testicular seminoma in 2005. We discuss the unusual presentation of these three rare events occurring in the same patient without known risk factors. PMID- 22053584 TI - Recurrent achalasia in a child with Williams-Beuren syndrome. AB - Williams-Beuren syndrome is a multysistem genetic disorder caused by the 1.6Mb hemizygous deletion involving the elastin gene in the region q11.23 of chromosome 7. The phenotype of Williams-Beuren syndrome is extremelly variable but the most common findings include cardiovascular disease, distinctive facies, mental retardation, a specific congitive profile, endocrine abnormalities, growth retardation and connective tissue abnormalities. Although gastrointestinal difficulties are one of the most constant and prominent finding of the syndrome, including gastro-esophageal reflux (GER), poor suckling, vomiting, constipation, prolonged colic, rectal prolapse, inguinal, umbilical and hiatal hernia, there have been no reports of achalasia in association with Williams-Beuren syndrome in the literature. We present the case of a boy with Williams-Beuren syndrome, achalasia and recurrent postoperative stenosis of the cardia. After Heller myotomy, the boy developed severe restenosis of the cardia with abundant adhesions which repeated after every treatment, five times in periods shorter than one month. Eventually, he developed GER, errosive gastritis and hiatal hernia which led to severe malnutrition and failure to thrive. Although the genetic defect causing Williams-Beuren syndrome might not be the direct cause of achalasia we suggest that the frequent development of severe restenosis of cardia due to tight adhesions could be the consequence of elastin gene haploinsufficiency and altered structure and function of elastic fibers in esophageal connective tissue. This case highlights the importance of early diagnosis of esophageal motor disorders in childhood which should be included in the differential diagnosis when a child with Williams-Beuren syndrome presents with dysphagia and/or regurgitation. PMID- 22053585 TI - Displacement of a mandibular incisor--an infrequent complication of mandibular fracture. AB - A case of a mandibular fracture with an unusual complication is reported. A 13 year-old boy was admitted four years after conservative treatment of a symphyseal fracture. He complained of recurrent swelling. A radiographic evaluation showed a horizontally laid permanent mandibular left lateral incisor (PMLLI) that had probably slid into the fracture line and provoked repetitive infection episodes. After a surgery, a clinical and radiological analysis showed satisfactory healing. PMID- 22053586 TI - Plausible mechanisms for brain structural and size changes in human evolution. AB - Encephalization has many contexts and implications. On one hand, it is concerned with the transformation of eating habits, social relationships and communication, cognitive skills and the mind. Along with the increase in brain size on the other hand, encephalization is connected with the creation of more complex brain structures, namely in the cerebral cortex. It is imperative to inquire into the mechanisms which are linked with brain growth and to find out which of these mechanisms allow it and determine it. There exist a number of theories for understanding human brain evolution which originate from neurological sciences. These theories are the concept of radial units, minicolumns, mirror neurons, and neurocognitive networks. Over the course of evolution, it is evident that a whole range of changes have taken place in regards to heredity. These changes include new mutations of genes in the microcephalin complex, gene duplications, gene co expression, and genomic imprinting. This complex study of the growth and reorganization of the brain and the functioning of hereditary factors and their external influences creates an opportunity to consider the implications of cultural evolution and cognitive faculties. PMID- 22053587 TI - Biochemical screening of fetal aneuploidies and neural tube defects by "double test" in Croatia: a 10 years' experience. AB - The aim of the study is to investigate the efficiency of the second-trimester biochemical screening, with maternal serum alpha-fetoprotein (MS-AFP) and free beta-subunit of human chorionic gonadotropin (free beta-hCG), during the ten-year period. The study included 11,292 of pregnant women between the 15th and 18th gestational week, who underwent screening from November 1996 to December 2006. The risk for trisomy 21 and trisomy 18 were calculated by computer software, based on a model which generated the final risk for fetal aneuploidies from the pregnant woman's a priori age risk and the likelihood ratio of the distribution of the biochemical markers, according to the second-trimester gestation. With the cut-off value of the final risk > or = 1:250, the detection rate for trisomy 21 was 75% (21/28). In women less than or equal to 35, the detection was 57.1% (8/14) and 92.9% (13/14) in those over 35 years, respectively. The detection rate of trisomy 18 was 50% (2/4). The results confirmed that the implementation of double-test, as non-invasive screening for fetal aneuploidies, should be accepted as a complementary method of antenatal care. PMID- 22053588 TI - From the history of Croatian dentistry: 100th anniversary of the birth of Professor Sime Kordic (1909-1984). AB - The aim of this study was to pay tribute to the memory of extraordinary Croatian Professor of children's and preventive dentistry Sime Kordic on the occasion of the 100th anniversary of his birth. The biography and work of this scientist and teacher were presented, as well as his researches about the history of dentistry and medicine in our coastal cities. On the bases of his published papers, we analyzed a significant role of Professor Sime Kordic for the development of dental medicine and promotion of health culture in Croatia. PMID- 22053589 TI - Role of rhinovirus infections in asthma. AB - Human rhinoviruses are not only the main pathogens responsible for the common cold, but are now recognized to have a major impact on asthma pathogenesis. There is evidence that rhinovirus infections play a role in asthma development, asthma exacerbations and, potentially, airway remodeling. Children who experience repeated rhinovirus-induced wheezing episodes in infancy have a significantly increased risk of developing asthma, even when compared to children who experience wheezing induced by respiratory syncytial virus. Rhinovirus is also the dominant virus type associated with acute exacerbations of asthma. The epithelial cell is the principal site of rhinovirus infection in both the upper and lower airways and there is strong evidence that virus-induced alterations of epithelial cell biology play a critical role in regulating clinical outcomes. This includes rhinovirus-induced epithelial generation of a variety of chemokines, cytokines and growth factors that likely play a role in viral modulation of airway inflammation. It has also become clear, however, that epithelial cells play an important role in the innate antiviral response to rhinovirus infection, raising the possibility that the relative induction of epithelial host innate antiviral responses versus proinflammatory responses may be one factor regulating the susceptibility of asthmatic subjects to virus induced disease exacerbations. Recent evidence has also highlighted that rhinovirus infection induces epithelial production of a number of growth factors and other mediators that could contribute to the development and progression of airway remodeling processes in asthma. The current article reviews our current state of knowledge in these areas. PMID- 22053590 TI - Omalizumab in allergic diseases, a recent review. AB - Omalizumab is a biological engineered molecule, targeting the Cepsilon3 domain of the IgE molecule. It binds with free IgE and prevents free IgE from attaching to high-affinity IgE receptor (FcepsilonRI) on effector cells such as mast cells, basophils and also on dendritic cells. The result is a blocking of mediator release from these cells and the inhibition of antigen presentation by dendritic cells. In addition, omalizumab downregulates FcepsilonRI expression on these effector cells. Omalizumab prevents early and late phase allergic reactions of skin and lungs. Omalizumab has been investigated extensively in moderate-to severe asthma in adults and children. It effectively reduces rates of asthma exacerbation, emergency visits for asthma and hospital admissions among these patients. Currently, omalizumab is primarily indicated for patients, age 6 years and over, with moderate to severe asthma (GINA step 4). Omalizumab was investigated in patients with seasonal allergic rhinitis (to ragweed, birch and grass pollens) and has been found to improve rhinitis symptoms and to reduce medication use among these patients. Administered together with allergen immunotherapy, omalizumab reduced incidence of side effects and rates of anaphylaxis from allergen immunotherapy. Omalizumab has been investigated in the treatment of food allergy, atopic dermatitis and urticaria. Despite benefits observed from these initial trials, it further deserves investigations to clarify optimal conditions for use in these conditions. Side effects from omalizumab were few, however, it requires careful considerations in administration of this agent. An observational period (up to 2 hours after the first three doses) and the availability of auto-injectable epinephrine are recommended. Pharmacoeconomics of omalizumab is briefly reviewed. Omalizumab represents a major breakthrough of translational medicine in allergy. PMID- 22053591 TI - Impairment of CD4+CD25+ regulatory T cells in C4-deficient mice. AB - OBJECTIVE: To investigate the association between deficiencies of early components in the classical complement pathway and the development of SLE. METHODS: Forty inbred C57BL/6J mice and 40 knockout C4 complement gene (C4KO) mice, which included 10 mice in each age group (2, 4, 6, and 8 months) were used. The enumeration of CD4+CD25+ Tregs frequencies in bone marrow, spleen and peripheral blood from both normal and C4KO groups were performed by flow cytometry. The expression levels of Foxp3 and TGF-beta in the same tested tissues were measured using real time PCR. The antinuclear antibodies (ANA) were semi quantitatively measured using ELISA. RESULTS: We report decreased frequencies of CD4+CD25+ Tregs and reduced expression levels of Foxp3 and TGF-beta, which efficiently program the development and function of Tregs, in lymphoid tissues and peripheral blood of C4KO mice. In this study, C4KO mice have higher titers of ANA than those of normal mice. Higher frequencies of mice positive for ANA are also found in older mice. CONCLUSIONS: The deficiency of the C4 gene induces the decreased numbers of Tregs that further increase the production of ANA resulting in the development of an autoimmune disorder. The outcomes of our study help us to understand the association between the deficiency of C4 in the classical complement pathway and development of autoimmune disorder via the role of Tregs. PMID- 22053592 TI - Association between CTLA-4 polymorphisms and the susceptibility to systemic lupus erythematosus and Graves' disease in Thai population. AB - BACKGROUND: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a cell surface molecule involved in the regulation of T cells. Single nucleotide polymorphisms (SNPs) of CTLA-4 gene are known to be associated with susceptibility to several autoimmune diseases, including systemic lupus erythematosus (SLE) and Graves' disease (GD). OBJECTIVE: The aim of this study was to determine whether the common SNPs +49A/G on exon1 and CT60A/G in 3'UTR of the CTLA-4 gene are associated with susceptibility to SLE and GD in Thai population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze these two SNPs in 151 patients with SLE, 132 patients with GD and 153 healthy controls. RESULTS: Our study showed that there were no statistically significant differences in the allele and genotype frequencies of +49A/G and CT60A/G SNPs between patients with SLE and healthy controls as well as patients with GD vs. healthy controls (P > 0.05). However, the GG genotypes of +49A/G and CT60A/G were likely to be risk factors (OR >1) for GD but not in SLE. The effect of the +49G allele was similar to that of an autosomal recessive gene in the presence of the GG genotype, when compared to AA and AG, with an OR of 1.58 (95% CI = 0.95-2.61, p = 0.061) in GD. We also observed a dose response effect of the CT60G allele on GD susceptibility with an OR of 1.43 for GG homozygous and 1.17 for AG heterozygous subjects, when compared to the AA genotype, although these were not statistically significant (P > 0.05). CONCLUSION: We found no association between two functional polymorphisms (+49A/G and CT60A/G) of the CTLA-4 gene and susceptibility to SLE and GD. However, the association study utilizing a larger sample size should be performed to confirm this. PMID- 22053593 TI - Correlation between TCRCalpha -560 C/T polymorphism and the clinical presentation of Uygur IgA nephropathy patients in XinJiang. AB - OBJECTIVE: To investigate the relationship between T cell receptor alpha chain constant gene (TCRCalpha) -560 C/T polymorphism and the clinical presentation of Uygur IgA Nephropathy patients in XinJiang. METHODS: TCRCalpha -560 C/T genotypes were determined by PCR-RFLP in 300 Chinese Uygur IgAN patients and 600 healthy Chinese Uygur control subjects. All subjects were classified, based on their genotype, into TT, CT and CC groups and their corresponding clinical presentation was analyzed. RESULTS: No significant difference was observed in the frequency of CC/CT/TT genotypes in patients and control subjects (chi2 = 0.904, P = 0.636). However, the incidence of intermittent microscopic hematuria and proteinuria is significantly higher in patients with CT genotype than CC and TT genotypes (chi2 = 33.978, P < 0.05). CONCLUSION: TCRCalpha-560 C/T gene polymerphism may be associated with the occurrence of intermittent microscopic hematuria and proteinuria in Chinese Uygur IgAN patients. PMID- 22053594 TI - Apoptosis, production of MMP9, VEGF, TNF-alpha and intracellular growth of M. tuberculosis for different genotypes and different pks5/1 genes. AB - BACKGROUND: A previous study of IS6110 RFLP and spoligotyping of M. tuberculosis isolates from 152 Thai patients with tuberculous meningitis revealed a significantly higher percentage (57%) of the Beijing genotype as compared to isolates obtained from pulmonary tuberculosis. We postulated that the M. tuberculosis Beijing genotype is likely to be more virulent than others. OBJECTIVES: Ten M. tuberculosis cerebrospinal fluid (CSF) isolates from five RFLP groups, together with different characteristics of pks15/1, M. tuberculosis H37Rv and M. bovis BCG, were investigated for their virulence in vitro. METHODS: In this study, THP-1 cells were used as host cells to determine the intracellular growth and the induction of MMP9, VEGF, TNF-alpha and apoptosis. Determinations of the cytokine production and apoptosis were based on available commercial kits using ELISA techniques. RESULTS: No significant difference in intracellular multiplication was found between the M. tuberculosis CSF isolates. Three isolates, consisting of 2 Nonthaburi and 1 heterogeneous isolate, were found to stimulate high TNF-alpha and MMP-9 production during the early infection period.They were isolated from 3 different patients, 2 of whom died with initial stages II and III. This result suggested that there might be an association between TNF-alpha and MMP-9 production that could account for the specific virulent nature of Nonthaburi strains. VEGF production was determined and comparable levels were found in all isolates. No significant apoptosis was detected in M. tuberculosis CSF isolates. No significant differences suggesting that the 2 Beijing strains are more virulent than the others were observed. CONCLUSION: The predominance of the Beijing strains in cases of tuberculous meningitis (TBM) in Thai patients is not a result of their hypervirulence. PMID- 22053595 TI - A single injection of 19 kda carboxy-terminal fragment of Plasmodium yoelii merozoite surface protein 1 (PyMSP1(19)) formulated with Montanide ISA and CpG ODN induces protective immune response in mice. AB - OBJECTIVE: To investigate the efficacy of a vaccine formulation of the 19 kDa conserved carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (PyMSP1(19)) formulated with CpG ODN 1826 and Montanide ISA51 or ISA720 when used to immunize mice by a single injection. METHODS: Groups of BALB/c mice were immunized parenterally with one, two or four injections with PBS or PyMSP1(19) formulated with CpG ODN in ISA51 or ISA720. Sera were collected weekly and assessed for total IgG and IgG subclass titers. Protection was tested by challenge infection with P. yoelii YM. RESULTS: Interestingly, single injection immunization showed the same kinetics of antibody responses as two- or four injection immunization. However, the peak antibody response induced by PyMSP1(19) in CpG ODN and ISA51 appeared earlier than that induced by PyMSP1(19) in CpG ODN and ISA720 (28 days vs 41 days). At day 63 after the first injection, the PyMSP1(19)-specific IgG antibody levels by single injection and four-injection immunizations were not different. However, the levels of the IgG2a antibody subclass were significantly lower by single injection immunization with PyMSP1(19) in CpG ODN and ISA720. The antibodies were sustained at high levels for at least 20 weeks. After challenge infection, all mice immunized by a single injection of PyMSP1(19) in CpG ODN and ISA51 survived with low-grade parasitemia, while 50% of mice immunized with PyMSP1(19) in CpG ODN and ISA720 died with high levels of parasitemia. CONCLUSION: These findings suggest that MSP1(19) immunization by a single injection can induce protective immunity, particularly when formulated with an appropriate strong adjuvant. PMID- 22053596 TI - Clinical manifestations and BTK gene defect in 4 unrelated Taiwanese families with Bruton's disease. AB - BACKGROUND AND OBJECTIVE: X-linked agammaglobulinemia (XLA, also called Bruton's disease) is is an X-linked recessive disorder characterized by recurrent bacterial infections, usually occurring in the first few years of life. Here, we report the results of a BTK gene mutation screening study that was performed in Taiwanese families with the BTK gene defect to further understand the inheritance patterns of XLA patients in Taiwan and to avoid new cases of XLA within families. MATERIALS AND METHODS: In this study, 52 members of 4 unrelated Taiwanese families with the BTK gene defect were enrolled. We studied the immunologic reports of 6 symptomatic living male patients with confirmed BTK gene defects and correlated the findings with their clinical symptoms. The genomic DNA of the subjects was subjected to direct sequencing mutation analysis. RESULTS: We screened 52 members of 4 unrelated Taiwanese families with the BTK gene defect for BTK gene mutation and found that there were 6 symptomatic living patients with a confirmed defect, 7 symptomatic deceased patients highly suspected to have had the defect and 11 asymptomatic female carriers. CONCLUSIONS: This is the first report in a series of the thorough screening for the BTK mutation and its carrier status in 4 unrelated Taiwanese families. One pedigree of our study comprises 4 generations. A complete BTK gene mutation study for the patient's family members is strongly suggested. PMID- 22053597 TI - Increased expression of aryl hydrocarbon receptor and interleukin 22 in patients with allergic asthma. AB - OBJECTIVES: We sought to determine whether the aryl hydrocarbon receptor (AhR) and interleukin (IL)-22 may be involved in the pathogenesis of the peripheral blood mononuclear cells (PBMCs) in allergic asthmatic patients and whether their expression may be related to the severity of the disease. METHODS: Blood samples were obtained from each subject with allergic asthma (n =18), controlled asthma (n = 17) and healthy controls (n = 12) respectively. The PBMCs were collected for AhR mRNA detection by real-time quantitative polymerase chain reaction (PCR). The plasma was collected for IL-22 protein detection by enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of AhR mRNA in PBMCs and IL-22 protein in plasma of patients with allergic asthma were higher than those in controlled asthma cases and healthy controls. The plasma concentrations of IL-22 had negative correlation with the predicted percentage of forced expiratory volume in the first second (FEV1%) and the percentage of FEV1 and forced vital capacity (FEV1/FVC%) and it was positively correlated with the asthma severity score (ASS) of the asthmatics. CONCLUSION: Our results suggested that both AhR and IL-22 might be involved in the pathogenesis of allergic asthma in human and the level of IL-22 might have some relationship with the severity of the disease. PMID- 22053598 TI - Association of TGF-beta1, IL-4 and IL-13 gene polymerphisms with asthma in a Chinese population. AB - BACKGROUND: Asthma is a common respiratory disease caused by genetic and environmental factors. It has been suggested that TGF-beta1, IL-4 and IL-13 play important roles in asthma. OBJECTIVES: We attempted to confirm the roles of TGF beta1, IL-4 and IL-13 polymorphisms in asthma in a Chinese population. METHODS: Five SNPs (rs1800469, rs2241712, rs2070874, rs20541 and rs1800925) in TGF-beta1, IL-4 and IL-13 were genotyped using the MassArray SNP genotyping system. Allelic and genotypic associations between these SNPs and asthma were evaluated using logistic regression analysis. RESULTS: The CT genotype of rs1800469 and T allele of rs20541 were significantly associated with asthma. Among atopic subjects, the CT genotype of rs1800469 and GA genotype of rs2241712 decreased the risk of asthma, while the CC genotype of rs2070874 showed a decreasing trend of asthma risk with a borderline significance. No significant association was found between rs1800925 and asthma. CONCLUSION: In the present study, we confirmed the association of rs1800469 in TGF-beta1 and rs20541 in IL-13 with asthma and found a trend toward association between rs2241712 in TGF-beta1 and rs2070874 in IL-4 with asthma among atopic subjects, suggesting TGF-beta1, IL-4 and IL-13 may be associated with the susceptibility and development of asthma in this Chinese population. PMID- 22053599 TI - Exercise-induced bronchoconstriction in rhinitis children without asthma. AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) is a condition that leads to limited participation in sports. Prevalence of EIB ranges from 5-20% in general population to 40 - 90% in asthmatic patients. But the prevalence among rhinitis children with EIB remains debatable. We aimed to determine the prevalence of EIB in nonasthmatic children with rhinitis. METHODS: A cross sectional study was performed on 53 rhinitis patients without known asthma who attended the Pediatric Allergy Clinic between March 2009 and February 2010. They all underwent physical examination, skin prick test, pulmonary function tests and an exercise challenge test (ECT) on a treadmill. A positive ECT was defined as a decrease in FEV1 > 10% after exercise. RESULTS: The patients' mean age was 12.3 +/- 2.6 years. Most of them (60.4%) had moderate to severe persistent rhinitis. Eleven out of 53 patients (20.7%) had EIB. The peak time for occurrence of EIB was 10 minutes after exercise. Most of the EIB episodes observed were of mild degree. Patients who had persistent symptoms and a short duration of rhinitis treatment prior to the ECT day had more positive ECT results (72.7% vs. 28.6%, p 0.013, 0.2 years vs.1.9 years, p 0.012, respectively). The history (Hx) was not a reliable means of identifying children who had EIB (ECT+/Hx+ 54.6%, ECT-/Hx+ 54.8%). There was no significant relationship between baseline pulmonary function and the decline in FEV1 after exercise. CONCLUSION: The prevalence of EIB in rhinitis children without asthma is 20.7%. History, physical examination and pulmonary function are insufficient to diagnose EIB. PMID- 22053600 TI - Cutaneous adverse reactions to sulfonamide antibiotics. AB - BACKGROUND: Sulfonamides are divided into two main groups which are sulfonamide antibiotics and sulfonamide non-antibiotics. The wide use of sulfonamide antibiotics leads to increasing incidence of sulfonamide cutaneous reactions. OBJECTIVE: The purpose of this study is to explore the cutaneous manifestations induced by sulfonamide antibiotics in a large number of Thai patients, including human immunodeficiency virus (HIV) and non-HIV infected individuals. The second purpose is to determine the risk factors for development of sulfonamide cutaneous reactions. METHODS: We retrospectively studied 191 patients with sulfonamide antibiotics cutaneous reactions attending the adverse drug reaction center, Siriraj Hospital, Bangkok between 2006 and 2010. RESULTS: Majority of the patients was female (59.7%).Maculopapular rash was the most common cutaneous manifestation (37.7%) followed by fixed drug eruption (22%), angioedema with or without urticaria (12.6%) and urticaria alone (12%). Among those with known HIV serology, maculopapular eruption occurred more frequently in the HIV positive group while fixed drug eruption occurred more frequently in HIV-negative group. CONCLUSION: From our study, there were no significant determination factors to develop serious drug reactions. However, the HIV-positive status and lower level of CD4 count had a tendency to increase risk of developing serious cutaneous reactions. PMID- 22053602 TI - Little women: more girls are starting puberty at 8. What are the causes--and risks? PMID- 22053601 TI - Frequency of the HLA-B*1502 allele contributing to carbamazepine-induced hypersensitivity reactions in a cohort of Malaysian epilepsy patients. AB - We describe the association of the HLA-B*1502 allele in 27 epilepsy patients (19 Malays, 8 Chinese) treated with carbamazepine (CBZ) at the UKM Medical Center (UKMMC), 6 with CBZ-Steven Johnson Syndrome (CBZ-SJS), 11 with CBZ-induced rash, 2 with suspected phenytoin-induced rash and 8 negative controls. Our study showed that 10 (6 Malay, 4 Chinese) patients were positive for HLA-B*1502. Out of the 10 patients, six were confirmed to have CBZ-SJS (p = 0.0006), while four patients developed a skin rash. However there were 6 Malay patients and 1 Chinese patient that developed a skin rash after CBZ administration who were not positive for the allele, indicating that there might be more that one allele associated with CBZ induced hypersensitivity. Another 2 patients were suspected of having phenytoin induced rash, instead of CBZ, and these patients did not have HLA-B*1502. In conclusion, this study confirmed the association of HLA-B*1502 with CBZ-SJS among Malaysian epilepsy patients, however there might be other genes that could be responsible for the CBZ-induced rash. PMID- 22053603 TI - Girls, interrupted: children pay a price when childhood ends too soon. PMID- 22053604 TI - Impact of hepatitis C virus infection on neutrophil oxidative burst function in hemodialysis patients. AB - Polymorphonuclear leukocyte (PMN) functions have been studied extensively in hemodialysis (HD) patients; however, results are contradictory and the mechanisms that modulate phagocytosis and oxidative burst are not completely understood. Hepatitis C virus (HCV) is a frequent complication of HD that may be associated with disturbed PMN function; however, the impact of HCV infection on neutrophil oxidative burst function in HD patients is unknown. We investigated Neutrophil oxidative burst function in 24 HD patients (15 HCV-positive and, 9 HCV-negative patients) before and after dialysis. HCV-RNA was detected by RT-nested PCR while, quantitative measurement of oxidative burst function was assessed by flowcytometry. Neutrophil Oxidised burst function was significantly diminished in HD patients as comapred to controls (P = 0.001, oxidised PMN (%); P = 0.02 mean flueresnce intensity, MFI), and in pre-dialysis as compared to post-dialysis samples (oxidised PMNs (%): 60.5 +/- 3.2 vs. 72.1 +/- 3.9, P = 0.02); (MFI: 352 +/- 42 vs. 500 +/- 50, P = 0.03). Alteration in Neutrophil oxidative burst function in the pre-dialysis samples was significant in HCV-positive patients as compared to HCV-negative patients (oxidized PMNs (%): 50 +/- 2.9 vs. 63 +/- 5.1, P = 0.02); (MFI: 291 +/- 31 vs. 438 +/- 64, P = 0.006). Marked reduction in E. coli induced burst in pre-dialysis samples compared to post-dialysis was found in HCV-positive when compared to HCV-negative patients (oxidized PMNs (%): 50 +/- 2.9 vs. 74.8 +/- 4.7, P = 0.001), (MFI: 291 +/- 31 vs. 493 +/- 63, P = 0.002). In conclusion, a possible role of concomitant HCV infection in alteration of Neutrophil oxidative burst function is highly suggested. PMID- 22053605 TI - The prognostic potential of bone marrow cyclin E and P27, in Egyptian patients with acute myeloid leukemia. AB - Cyclin E and the cyclin dependent kinase inhibitor P27 are two important regulators of the G1-S transition modulating the activity of cyclin-dependent kinases. Aberrations in the cell cycle control are often observed in tumors and might even be mandatory in tumor development. There are few molecular biologic determinants that may be prognostic for patients with acute myeloid leukemia (AML). To investigate the importance of cell cycle defects in AML, the cellular levels of cyclin E and the cyclin-dependent kinase inhibitor P27 (Kip 1) were evaluated in thirty AML patients (11 males and 19 females) diagnosed by standard clinical, morphological and immunophenotypic criteria and staged according to the FAB classification. Using immunoblot analysis, cyclin E and P27 were detected in blast cells of AML patients who were then treated by the standard AML chemotherapeutic protocol and were followed up. With respect to cyclin E, it was detected in 9/30(30%) AML cases among them 13.3% (4/30 cases) exhibited very strong bands while 16.6% (5/30 cases) showed faint bands. Cyclin E was high among M4/M5 cases and low among M3 cases and showed a statistically significant positive correlation with percentage of blast cells, aberrant phenotype and abnormal karyotype at diagnosis. It also showed a significant negative correlation with complete remission (CR) rates. All our AML cases exhibited P27 at low and high levels as seen in 19/30 (63.4%) and 11/30 (36.6%) cases, respectively. P27 showed a statistically significant negative correlation to the percentage of blasts at diagnosis and a significant positive correlation with achievement of CR. A significant negative correlation between P27 and cyclin E (P < 0.004) was observed as well. The present study suggested that levels of cell cycle regulators cyclin E and P27 can be used as a useful prognostic molecular markers in AML patients. PMID- 22053606 TI - Effect of surgically-induced weight loss on inflammatory mediators and peripheral blood monocyte CD11b expression in morbid obesity. AB - Obesity is characterized by a state of chronic mild inflammation, with raised circulating levels of inflammatory markers. Expression and release of inflammation-related adipokines, generally, rise as adipose tissue expands. In the present study we evaluated the level of serum mediators concerned in inflammation and monocyte activation (TNF-alpha, hs-CRP, MCP-1) together with percentage of CD11-b expression on monocytes in a group of morbidly obese individuals (n = 20) before and (3-6 months) after restrictive surgery, and in 15 healthy normal weight individuals. Serum MCP-1, TNF-alpha and hs-CRP were assayed by enzymatic immunoassay, while the percentage of CD11b expression on monocytes was assayed by flow cytometry. The total lipid profile and random blood glucose levels were also assessed. Morbidly obese individuals ( before surgical weight loss) had significantly increased levels of MCP-1, TNF-alpha, hs-CRP, CD11b expression on monocytes as compared to controls (P < 0.01). Levels of MCP-1, TNF alpha, hs-CRP were significantly decreased 3 to 6 months after restrictive surgery than before the operation (P < 0.01). hs-CRP, MCP-1 and TNF-alpha were positively correlated versus each other. TNF-alpha and hs-CRP also showed positive correlation with the body mass index. Our data suggested that the studied serum and monocyte parameters may link obesity with systemic inflammation and metabolic disorders. The interactions of MCP-1, CD11b and other inflammatory parameters might provide the basis for development of new therapies for this syndrome. PMID- 22053607 TI - Predictors of avascular necrosis of the hip in Emiratis patients with systemic lupus erythematosus. AB - Symptomatic avascular necrosis (AVN) of the hip is a known complication of systemic lupus erythematosus (SLE). Data on the prevalence of bone avascular necrosis (AVN) in Arab SLE patients are limited. We conducted a cross-sectional and retrospective case-control study on 126 SLE patients from Dubai to determine prevalence and predictors of symptomatic hip AVN. 8.7% of our lupus cohort demonstrated evidence of symptomatic hip AVN and had longer disease duration, higher cumulative steroid dose, and received cyclophosphamide and mycophenolate mofetil more often than the SLE patients without AVN (controls). Skin manifestations, serositis, lupus nephritis, neuropsychiatric lupus, and sero positivity for autoantibodies: anti-DNA, Anti-Sm, and antiphospholipid antibodies were higher in patients than controls. Administration of hydroxychloroquine prior to onset of AVN was less frequent in cases than controls. In conclusion, disease activity, steroids, cytotoxic drugs, and antiphospholipid antibodies are important predictors of symptomatic AVN in Emirati patients with SLE, Hydroxychloroquine may play a protective role against developing AVN in Emiratis with SLE. Controlled longitudinal studies are essential to validate these findings. PMID- 22053608 TI - Prognostic value of quantitative-PCR versus serology for detection of CMV in pre- and post- transplantation patients. AB - Two hundred-twenty six pre- and post- kidney transplantation patients were screened for CMV. They were categorized into three groups I: Eighty-five dialysis patients suffering from chronic renal failure, II: Sixty -two end stage renal disease patients prepared for transplantation, and III: Seventy-nine post-kidney transplant patients under immunosuppressive and cytotoxic therapy. The last group was subdivided according to clinical presentation into asymptomatic, mild, and invasive CMV disease subgroups. A control group comprised of fifty-two apparently healthy kidney and blood donors were also included. Serum and plasma samples were utilized for detection of anti-CMV antibodies by EIA, and determination of CMV viral load by quantitative-PCR respectively. QT-PCR results revealed high viral load; (4000-10.000 copy/ml) in 16 (100%) kidney recipient with invasive CMV disease, While only 4 (25%) of them were positive for IgM anti-CMV. Another ten patients with symptoms of CMV syndrome were found CMV-PCR positive with low viral load (436-3070 copy/ml) and all were negative for IgM anti-CMV. On the other hand, no CMV viral load was detectable among end-stage renal disease patients, although 6/62 (9.7%) were positive for IgM anti-CMV. All subjects were positive for IgG anti-CMV. It is concluded that QT-PCR rather than serology should be used for monitoring of CMV infection in pre- and post-transplantation patient. PMID- 22053609 TI - Pre-, intra- and post-operative plasma levels of soluble P-selectin in diabetics under thoracic paravertebral block versus general anaesthesia. AB - Platelet activation that occur after tissue injury increases the expression of P selectin. General anaesthesia and surgery may lead to peri-or post-operative hypercoagulability state that may lead to thrombotic complications, especially in high risk patients as diabetics. Administration of local anaesthesia was suggested to limit this hypercoagulability. The aim of this work was to evaluate the pre-, intra-and postoperative plasma levels of soluble P-selectin, as a predictor of thrombotic events, in diabetics receiving paravertebral block versus general anaesthesia during mastectomy operation for cancer breast. Forty type-2 diabetic females were included. They were randomly divided into two equal groups: group I received general anaesthesia and group II received thoracic paravertebral block. All females were subjected to preoperative thorough clinical examination, electrocardiography and laboratory investigations including complete blood picture, prothormbin activity, glycated hemoglobin A1c, fasting plasma levels of glucose, creatinine, lipid profile and alanine aminotransferase activity. Creatine kinase (CK), total and CK-MB, activities were also done preoperatively and six hours postoperatively. Plasma soluble(s) P-selectin levels were estimated preoperatively, 15 minutes after skin incision and one hour postoperatively. The results revealed that the preoperative plasma P-selectin levels did not significantly differ in the two groups. Its intra-and postoperative levels showed significantly higher levels in both groups than those preoperative, but the increase in group II is significantly less than those in group I. In conclusion, in high risk patients as diabetics undergoing major surgery, the use of paravertebral block is preferable as a good and effective alternative to general anaesthesia, to reduce the possibility of occurrence of thrombotic complications. PMID- 22053610 TI - Angiogenic factor VEGF and its relationship with biological prognostic markers in chronic lymphocytic leukemia. AB - B-CLL is a heterogeneous disease, distinguishing between good and poor prognosis represents a challenge to hematologists. The present study aimed to assess the relative merit of VEGF as a prognostic factor in CLL and to correlate it with other prognostic factors as CD38 & sP53 in the different stages of the disease. The median values of CD38%, sP53 and VEGF were significantly higher in both high and intermediate risk subgroups of the modified Rai staging system when compared to low risk subgroup. There was a statistically significant positive correlation between CD38% and VEGF in all subgroups. However, positive correlation between VEGF and sP53 was only observed in the high risk subgroup. The strong correlation between CD38 and VEGF in CLL patients, suggests the possibility that angiogenic factors might contribute to the more aggressive clinical behavior of CD38+ CLL. This could provide a rationale for the use of antiangiogenic agents in CD38+ CLL. PMID- 22053611 TI - Risk factors and immune response to hepatitis E viral infection among acute hepatitis patients in Assiut, Egypt. AB - Hepatitis E virus (HEV) infection is a common cause of acute viral hepatitis (AVH) in Egypt. We aimed to identify risk factors of HEV among acute hepatitis cases, measure HEV specific immune response to differentiate between symptomatic and asymptomatic infections. The study included symptomatic acute hepatitis (AH) patients (n = 235) and asymptomatic contacts (n = 200) to HEV cases. They completed a lifestyle questionnaire, screened for common hepatotropic viruses. Blood and serum samples were collected from patients and contacts after onset of disease and follow-up samples collected until convalescence. PBMC were separated and tested for specific HEV T-cell response by INF-gamma ELISPOT assay. Serum samples were tested for IgM and IgG anti-hepatitis E virus by ELISA. IgM antibodies to HAV were detected in 19 patients (8.1%), 37 (15.7%) with HBV, 10 (4.3%) with HCV. HEV infection was identified in 42 (16%) patients with AVH. Of the 200 contacts, 14 (7%) had serological evidence of recent HEV asymptomatic infection, showed stronger CMI responses than HEV infected subjects (2540 +/- 28 and 182 +/- 389 ISCs/106 cells, respectively; P < 0.05). In conclusion, HEV is a major cause of AVH in Egypt. Asymptomatic HEV patients are likely to have stronger immune responses including CMI responses, than symptomatic cases. PMID- 22053612 TI - Serum pentraxin 3 and interleukin-6 are associated with subclinical atherosclerosis in recent-onset rheumatoid arthritis. AB - Subclinical atherosclerosis is increased in patients with rheumatoid arthritis (RA), as chronic systemic inflammation leads to accelerate atherosclerosis and increase arterial stiffness in theses patients. This study aimed to evaluate the association of serum interleukin-6 (sIL-6) and serum pentraxin 3(sPTX3) with subclinical atherosclerotic in patients with recent-onset rheumatoid arthritis. Sixty patients with recent onset RA (12-24 months) and 20 controls were investigated. Carotid ultrasound examination, assays for lipid profile, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, sPTX3 and sIL-6 were done. RA patients demonstrated significantly higher carotid intima-media thickness (cIMT) values and increased carotid plaques than the control (P < 0.001 and P = 0.02, respectively). Levels of ESR, CRP, sPTX 3 and sIL-6 were significantly higher in RA patients than controls. RA related risk factors (disease duration, CRP, ESR, and duration of treatment with steroids), as well as sPTX 3, sIL-6 and cIMT were significantly higher in RA with atherosclerotic carotid plaques compared to those without atherosclerotic carotid plaques (all < 0.05). It is concluded that accelerated atherosclerosis in patients with recent-onset RA is associated with elevated levels of CRP, sPTX 3 and sIL-6. PMID- 22053613 TI - TNF-alpha and CXCL-10 correlation with insulin resistance in patients with chronic hepatitis C virus infection. AB - There are increasing reports of association between HCV infection and type-2 diabetes mellitus. Although the mechanism by which this association remains uncertain, development of insulin resistance may explain this association. We investigated the association of TNF-alpha and CXCL-10 with insulin resistance in HCV infected patients. Forty-four non-diabetic chronic hepatitis C patients and twenty healthy individuals were included. Fasting blood was used for glucose and insulin measurements. Diagnosis of insulin resistance (IR) was based on a mathematical means by the homeostasis model assessment score-insulin resistance index (HOMA-IR). Serum insulin, TNF-alpha and CXCL-10 levels were measured by enzyme linked immunosorbent assay (ELISA). Quantitative measurement of hepatitis C virus was performed by a standardized real time PCR assay. The HCV patients demonstrated a significant increase in serum TNF-alpha, CXCL-10, and HOMA-IR values as compared to normal controls. HOMA-IR level positively correlated with hepatitis C viral load, TNF-alpha and CXCL-10. It is concluded that, TNF-alpha, CXCL-10 correlate with IR and may play a role in the development of type-2 diabetes mellitus in chronic hepatitis C infected patients. PMID- 22053614 TI - Henneguya cynoscioni sp. n. (Myxosporea: Bivalvulida), an agent of severe cardiac lesions in the spotted seatrout, Cynoscion nebulosus (Teleostei: Sciaenidae). AB - A new myxosporean species, Henneguya cynoscioni sp. n., is described from the spotted seatrout, Cynoscion nebulosus (Cuvier) (Sciaenidae) as a causative agent of cardiac henneguyosis. This new myxosporean species is characterized by the morphology of spores and the sequence of SSU rDNA. Examination of 227 spotted seatrout from four South Carolina estuaries in 2008-2010 revealed a 33.5% total prevalence of H. cynoscioni. Henneguya cynoscioni produces lesions in the bulbus arteriosus, its specific site of infection. The severity of lesions and their impact on the bulbus arteriosus is proportional to the number of plasmodial stages developing in this segment of the heart, being most pronounced in host reaction directed against spores liberated from plasmodia. PMID- 22053615 TI - Descriptions of two new freshwater neotropical species of Rhinebothrium (Cestoda: Rhinebothriidea) from Potamotrygon motoro (Chondrichthyes: Potamotrygonidae). AB - Two new species of Rhinebothrium (Cestoda, Rhinebothriidea) from potamotrygonid stingrays in the Neotropical region are herein described, which raises the total number of Rhinebothrium species known from Neotropical freshwaters to five. Rhinebothrium corbatai sp. n., and Rhinebothrium mistyae sp. n. were both collected from Potamotrygon motoro (Muller et Henle), captured in four tributaries of the Parana River in Santa Fe Province, Argentina. The new species can be distinguished from their congeners, and from each other, by a combination of various features, including worm size (length and number of proglottids), number of loculi per bothridium, microthrix pattern, size of the cirrus sac, and the extent of the vas deferens. The discovery of these new species from P. motoro supports the pattern of high host specificity in this cestode genus, and reinforces the notion that some of the previous records of the enigmatic R. paratrygoni may correspond to new species of Rhinebothrium yet to be described. PMID- 22053616 TI - Hemipristicola gunterae gen. n., sp. n. (Cestoda: Tetraphyllidea: Phyllobothriidae) from the snaggletooth shark, Hemipristis elongata (Carcharhiniformes: Hemigaleidae), from Moreton Bay, Australia. AB - Helminthological examination of the snaggletooth shark, Hemipristis elongata (Klunzinger) (Carcharhiniformes: Hemigaleidae), from Moreton Bay, Queensland, Australia, yielded a phyllobothriid genus and species previously unknown to science. Hemipristicola gunterae gen. n., sp. n. is described here, and is placed in the subfamily Phyllobothriinae Braun, 1900. Of the other phyllobothriid genera, the new genus most closely resembles Paraorygmatobothrium in that both genera possess bothridia with a single loculus and apical sucker, post-vaginal testes and lateral vitellarium. Hemipristicola, however, differs from Paraorygmatobothrium in the morphology of the proximal bothridial surface microthrix, possessing serrate gladiate spinitriches with marginal serrations restricted to the distal half of the blade, and in the possession of a more extensive uterus, extending anteriorly from the anterior margin of the ovary to well past the level of the cirrus-sac. The new genus also differs from Paraorygmatobothrium by possessing testes that are more than one layer deep. Hemipristicola gunterae further differs from Paraorygmatobothrium species found in hemigaleid sharks in possessing vitelline follicles arranged in two lateral bands that are restricted to the lateral margins of the proglottid and not possessing a cephalic peduncle. Bayesian inference analysis of partial 28S rDNA data shows that H. gunterae forms a sister taxon to species of Paraorygmatobothrium. These two genera were resolved with high posterior probability support in the analysis. Hemipristicola gunterae is only the second phyllobothriid species to be described from Hemipristis elongata from Australian waters, and the fourth from the Australian hemigaleids. PMID- 22053617 TI - Revision of Khawia spp. (Cestoda: Caryophyllidea), parasites of cyprinid fish, including a key to their identification and molecular phylogeny. AB - Monozoic cestodes of the genus Khawia Hsu, 1935 (Caryophyllidea: Lytocestidae), parasites of cyprinid fish in Europe, Asia, Africa and North America, are revised on the basis of taxonomic evaluation of extensive materials, including recently collected specimens of most species. This evaluation has made it possible to critically assess the validity of all 17 nominal species of the genus and to provide redescriptions of the following seven species considered to be valid: Khawia sinensis Hsu, 1935 (type species); K. armeniaca (Cholodkovsky, 1915); K. baltica Szidat, 1941; K. japonensis (Yamaguti, 1934); K. parva (Zmeev, 1936); K. rossittensis (Szidat, 1937); and K. saurogobii Xi, Oros, Wang, Wu, Gao et Nie, 2009. Several new synonyms are proposed: Khawia barbi Rahemo et Mohammad, 2002 and K. lutei Al-Kalak et Rahemo, 2003 are synonymized with K. armeniaca; K. coregoni Kritscher, 1990 with Caryophyllaeus laticeps (Pallas, 1781) (family Caryophyllaeidae); K. cyprini Li, 1964 and K. iowensis Calentine et Ulmer, 1961 with K. japonensis; K. dubia (Szidat, 1937) (syn. Bothrioscolex dubius Szidat, 1937) with K. rossittensis; and Tsengia neimongkuensis Li, 1964 and T. xiamenensis Liu, Yang et Lin, 1995 with K. sinensis. Khawia prussica (Szidat, 1937) (syn. Bothrioscolex prussicus Szidat, 1937) is considered to be species incertae sedis, but its morphology indicates it may belong to Caryophyllaeus Gmelin, 1790 (Caryophyllaeidae). The molecular analysis of all seven valid species, based on comparison of sequences of two nuclear ribosomal and two mitochondrial genes, has shown that the species form three major groups clustered according to their fish hosts. Five species from common and crucian carp and goldfish were grouped together, whereas K. armeniaca from barbels (Barbinae) and K. baltica from tench (Tinca) formed separate clades. In contrast, geographical distribution does not seem to play a crucial role in grouping of individual taxa. A phylogenetic tree based on morphological characters was incongruent with that inferred from molecular data, which indicates that some morphological traits may be homoplastic. A key to identification of all species of Khawia based on morphological characteristics is provided. PMID- 22053618 TI - Two new species of Rhabdochona (Nematoda: Rhabdochonidae) from freshwater fishes in Thailand. AB - Two new species ofrhabdochonid nematodes are described from the intestine of freshwater fishes in Chiang Mai Province, northern Thailand: Rhabdochona (Rhabdochona) pseudomysti sp. n. from the catfish Pseudomystus siamensis (Regan) (Bagridae, Siluriformes) in the Fang Brook, a tributary of the Kok River (the Mekong River basin), Fang District and Rhabdochona (Globochona) thaiensis sp. n. from the cyprinid Mystacoleucus marginatus (Valenciennes) (Cyprinidae, Cypriniformes) in the Ping River (the Chao Phraya River basin), Muang District. Rhabdochona pseudomysti is mainly characterized by simple, leaf-like oval deirids (a unique feature among Rhabdochona spp.), a prostom with 14 anterior teeth, the presence of basal prostomal teeth, the length ratio of the muscular and glandular portions of oesophagus (1:2.1-2.6), an unusually long left spicule (1.10-1.22 mm), length ratio of spicules (1:11.5-14.7), arrangement of genital papillae, and conspicuously elevated vulval lips. Rhabdochona thaiensis differs from other representatives of the subgenus Globochona Moravec, 1972 possessing caudal projections on the tail tip in that it has only 2 claw-shaped projections located ventrally on the tail tip of both males and females; the species is mainly characterized by the presence of distinct pseudolabia, 8 anterior prostomal teeth, absence of basal teeth, bifurcated deirids, length ratio of the muscular and glandular portions of oesophagus (1:11.3-11.9), conspicuously short (135-141 microm) left spicule, arrangement of genital papillae, and somewhat elevated vulval lips. Fully developed eggs of R. pseudomysti and R. thaiensis remain unknown. These are the first nominal species of Rhabdochona reported from Thailand. PMID- 22053619 TI - A new species of Taeniacanthus (Copepoda: Taeniacanthidae) parasitic on two pufferfish species, Marilyna meraukensis and M. darwinii (Teleostei: Tetraodontidae), from Australia. AB - A new species of Taeniacanthidae (Copepoda, Cyclopoida), Taeniacanthus kiemae sp. n., is described based on adult female and male specimens collected from the branchial cavity wall of Marilyna meraukensis (de Beaufort) and M. darwinii (Castelnau) (Teleostei, Tetraodontidae) caught in Australian waters. The new species differs from its congeners by having the following combination of characters in the adult female: (1) maxilla armed with a stout terminal process and two small elements; (2) multiple rows of spinules on the large pectinate process of the antenna; (3) an extremely long and thin maxilliped claw; (4) second exopodal segment of leg 1 with eight setae; (5) third exopodal segment of leg 3 with three spines and four setae; (6) third exopodal segment of leg 4 with three spines and two setae; and (7) each spine on the free exopodal segment of leg 5 with a subterminal flagellum. Taeniacanthus kiemae is the second copepod species reported from M. meraukensis and M. darwinii and the first taeniacanthid species reported from pufferfishes in Australia. PMID- 22053620 TI - Natural and anthropogenic factors shape metazoan parasite community structure in mummichog (Fundulus heteroclitus) from two estuaries in New Brunswick, Canada. AB - Previously published multidisciplinary studies in the Miramichi and Bouctouche rivers (New Brunswick, Canada) noted significant changes in fish health parameters, including elevated tissue levels of organic contaminants and a wide range of physiological disturbances, in mummichog Fundulus heteroclitus (L.) from a site on the Miramichi River that received bleached kraft pulpmill and municipal effluent. The present study reports differences in the abundance of individual parasite species, as well as parasite infracommunity and component community composition, in mummichog from both rivers. These differences were evaluated in relation to host (size, condition, immune function, tissue organochlorine contaminant levels) and environmental (faecal coliform counts, salinity, temperature) data derived from the previously published studies. Overall, 18 parasite species were identified, the most common of which were Ascocotyle sp. larv., Ornithodiplostomum sp. larv., Posthodiplostomum sp. larv., and Proteocephalus filicollis (Rudolphi, 1802). There were broad differences in parasite community structure and composition between rivers and within rivers, the most prominent pattern being a pronounced difference between sites in the upper and lower estuary of each river that was likely driven by salinity. Mean infracommunity richness was also positively related to faecal coliforms (considered here as a surrogate measure of eutrophication via municipal sewage), and both were highest at the most polluted site. We noted no other significant relationships. Thus our data suggest that the parasite communities in these two estuaries were primarily structured by large upstream/downstream ecological gradients in salinity, and secondarily by eutrophication due to pollution by municipal and industrial effluents. Overall, our results highlight the value of coordinated multidisciplinary studies for understanding the factors that shape parasite abundance and community structure. PMID- 22053621 TI - Does oxidative stress affect the activity of the sodium-proton exchanger? AB - INTRODUCTION: Accumulation of reactive oxygen species (ROS) takes place in patients with chronic renal failure (CRF). Oxidative stress causes disorders in the activity of the sodium-proton exchanger (NHE). Studies on NHE in CRF produced results that are discrepant and difficult to interpret. The aim of this study was to demonstrate that oxidative stress had an effect on the activity of NHE. METHODS: We enrolled 87 subjects divided into 4 groups: patients with CRF treated conservatively; patients with CRF hemodialyzed without glucose--HD-g(-); patients with CRF hemodialyzed with glucose--HD-g(+); controls (C). The activity of NHE, the rate of proton efflux V(max), Michaelis constant (Km), and the concentration of thiobarbituric acid-reactive substances (TBARS, an indicator of oxidative stress) in plasma, as well as the concentration of reduced glutathione in blood were determined. RESULTS: The concentration of TBARS was significantly higher in hemodialyzed patients before and after dialysis and in patients with CRF on conservative treatment in comparison with group C. TBARS in plasma correlated negatively with VpH(i)6.4 in group C and with V(max) and VpH(i)6.4 after HD in group HD-g(-). We found that the concentration of creatinine correlated with TBARS (p < 0.0001; r = +0.51) in the conservatively treated group. CONCLUSION: We observed a marked oxidative stress and decreased NHE activity when dialysis was done without glucose, whereas patients dialyzed with glucose demonstrated a relatively low intensity of oxidative stress. PMID- 22053622 TI - [The association between gastroesophageal reflux and recurrent lower respiratory tract infections and bronchial asthma in children]. AB - INTRODUCTION: It is well known that gastroesophageal reflux (GER) coincides with chronic diseases of the lower respiratory tract. However, the impact of effective management of gastroesophageal reflux on the course of coexisting pathologies of the lower respiratory tract has not been unequivocally evaluated. This study was undertaken to assess the impact of treatment of gastroesophageal reflux on the course of recurrent lower respiratory tract infections and bronchial asthma in children. MATERIAL AND METHODS: We enrolled 76 children, 38 boys and 38 girls, aged 1-204 months (median: 66.5 months). All children had clinical symptoms of gastroesophageal reflux. The children were allocated to three groups: Group I: recurrent lower respiratory tract infections (33 children); Group II: bronchial asthma (23 children); Group III: no chronic respiratory tract disease (20 children). Groups were similar with respect to age and gender. Upper gastrointestinal tract scintigraphy and endoscopy were performed in all children. The children were followed for 1-23 months (mean: 7 months). In most cases, GER was managed conservatively, except for four children who were operated. RESULTS: Complete or partial resolution of GER symptoms was seen in 89% of patients, no change was noted in 9%, and progression was seen in the remaining 2% of children. Treatment of GER was accompanied by alleviation of respiratory symptoms in 84% of children (group I and II). CONCLUSIONS: Effective therapy of gastroesophageal reflux decreases the frequency of recurrent lower respiratory tract infections and improves asthma control. PMID- 22053623 TI - [Monitoring of nosocomial infections in intensive care units]. AB - INTRODUCTION: Intensive care units (ICUs) are distinguished by the use of specialist medical procedures based on invasive monitoring and mechanical support of dysfunctional organs or systems of the body. Patients at ICUs represent a specific group due to the fact that many of them will suffer infections in the course of hospitalization which pose a threat to their health or life and exert an impact on the therapeutic success. The aim of this study was to perform a prospective analysis of hospital infections at the intensive care unit, to determine etiologic factors and clinical forms of infection, as well as to define infection risk factors specific for the patient or related to the diagnosis, treatment, and specific procedures at the unit. MATERIAL AND METHODS: The study was done in 234 patients hospitalized at the Department of Intensive Medical Care, Pomeranian Medical University, Independent Public Clinical Hospital No. 1 in Szczecin during one year. An infection registration card was created for each patient. Samples for microbiological tests were routinely collected once a week or in the event of suspected infection. CONCLUSIONS: 1. The prospective clinical, microbiological, and epidemiologic analysis performed at the ICU demonstrated that: a) infections were diagnosed in approx. 45% of the patients, b) the most common clinical forms of infection were: pneumonia (87.5%), sepsis (44.2%), and urinary tract infection (36.5%). Two to four clinical forms of infection were seen in approx. 64% of the patients, c) the most common etiologic factor of infection, irrespectively of the clinical form, were Gram-negative bacteria, predominantly Acinetobacter baumannii and Pseudomonas aeruginosa, d) patient related infection risk factors of importance included male gender and overweight/obesity, e) procedure--related infection risk factors considerably contributing to infection included: bronchial toilet, tracheostomy, drainage of body cavities, feeding through a gastric tube, gastrostomy, central vessel cannulation, parenteral feeding, and chemotherapy. 2. The understanding of the prevalence and circumstances of infections at ICUs will help verify standards of preventive and therapeutic management at the ICU and may contribute to adequate control and efficient treatment of infections. PMID- 22053624 TI - Trans fatty acids and their role in inflammation and cardiovascular disease. AB - Trans fatty acids (TFAs) are not synthesized in the human body but are found in many food products. Several reports have shown that high consumption of TFA is unrelated to the risk of metabolic diseases. Increased consumption of TFAs was reported to be positively correlated with risk of ischemic heart disease, as well as with initiation and progression of atherosclerosis. This work focuses on dietary sources and effects of TFA on the atherosclerotic process. PMID- 22053625 TI - [Diagnostic value of 99mTc-MIBI myocardial perfusion SPECT in women with suspected coronary artery disease]. AB - INTRODUCTION: Coronary artery disease is the leading cause of mortality in the general population. Women constitute a special group of patients due to the fact that clinical presentation in women is less characteristic and diagnostic tests are more difficult to interpret. The representation by men in clinical trials grossly exceeds that by women and the number of investigations conducted selectively in women remains too small. The aim of this study was to evaluate the diagnostic usefulness of myocardial perfusion scintigraphy (SPS) with 99mTc-MIBI in women with suspected coronary artery disease, particularly in those with nondiagnostic or positive stress electrocardiography (SEKG), to assess the prognostic value of SPS during a 4-year follow-up targeting serious cardiac events, and to compare the results of SPS with SEKG and coronary angiography. MATERIAL AND METHODS: We enrolled 230 women with a moderate probability of coronary artery disease estimated on the basis of clinical scales and SEKG. A 2 day stress/ rest SPS was done in all patients. The clinical course was determined in 157 patients. It was found that the 1-year risk of a serious cardiac event in women with an abnormal SPS was 7.9%, as opposed to 1.7% in women with a normal SPS. RESULT: The results confirmed the high prognostic value of SPS in predicting serious cardiac events (p = 0.01). There was no statistically significant correlation between ambulant SEKG and SPS (p = 0.06). Similarly, the results of SEKG did not correlate with serious cardiac events (p = 0.35). The prognostic value of SPS found by us was high, and moreover, SPS turned out to be superior over SEKG in our study group. CONCLUSION: Myocardial perfusion scintigraphy emerged as a good diagnostic tool in women with suspected coronary artery disease. Myocardial perfusion scintigraphy is helpful in verifying the need for further diagnostic tests in women, especially with positive or nondiagnostic SEKG. PMID- 22053626 TI - [Cigarette smoking as a promoting factor for nonspecific inflammatory bowel disease]. AB - Nonspecific inflammatory bowel diseases represent serious and chronic pathologies of the gastrointestinal tract. Even though the etiology of these diseases has not been fully elucidated, it is known that environmental factors like cigarette smoking may induce and exacerbate their course. Many substances in cigarette smoke have a modulatory effect on the immune system through a change in the composition of pro-/anti-inflammatory cytokines witch plays its part in the development of inflammation. Moreover, cigarette smoke contains reactive oxygen species which may combine with decreased activity of antioxidant enzymes to produce an additional proinflammatory effect. It is interesting that cigarette smoke has a different effect on the course of Crohn's disease compared with ulcerative colitis. PMID- 22053627 TI - [Trauma in cycling--case report and review of the literature]. AB - The authors present a review of trauma in tourist and competitive cycling in Poland in comparison with reports in the literature. Groups of injuries are discussed with a focus on their frequency and threat to life and health. The authors present a case of a road cycler colliding with a car, his first aid, evacuation, and treatment at a hospital. This case, as well as accidents of other competitive cyclers, are analyzed by the authors to demonstrate ways of reducing trauma in cycling. Most importantly, competitive and tourist cyclers should always wear cycle helmets as they reduce head trauma, the main life-threatening trauma in this sport. PMID- 22053628 TI - [The effect of new generation materials used in reconstructive dentistry on the oral cavity environment]. AB - PURPOSE: Loss of teeth impairs the functioning of the stomatognathic system, complicates chewing, interferes with speech, and alters the patient's appearance. Reconstruction of the defects with implants or fixed dentures often proves impossible and removable dentures remain the sole option in such cases. Continuous progress in materials science, as well as growing demands and expectations from both dentists and patients drive the efforts of manufacturers of dental materials towards improved and innovative products. The requirements for prosthetic materials are the same as for medications. The main goal is biological neutrality or, at least, biological tolerance. Polymers and metal alloys are being constantly modified to better suit these demands. T.S.M. Acetal Dental in one of the monomer-free polymers that have recently been introduced to prosthodontics. This product has not yet been the object of extensive clinical and laboratory studies in Poland. Wironit extrahart chromium-cobalt alloy and Vertex R.S. Acrylic have been certified by the Polish Ministry of Health for use in Poland. Therefore, these products were selected for reference purposes in the present study. As the certificate for T.S.M. Acetal Dental is lacking, the product was subjected to experiments in animals and to physicochemical tests. MATERIAL AND METHODS: The following physicochemical properties were examined: mechanical strength, fatigue limit, abrasiveness, and contact angle. Histopathology of animal material was directed at the reaction of tissues to the prosthetic materials. Adhesion of bacteria and fungi to the materials was examined. The usefulness of acetal resin in prosthetic practice and the biofunctionality of dentures made of the resin were assessed as well. RESULTS: Mechanical properties of acetal resin seen in the static bending test were clearly inferior to metal alloys. However, the results of dynamic tests were in favor of acetal resin compared with metal alloy. Abrasiveness of acetal resin exceeded that of the metal alloy. The values of contact angle were distinctly lower for resin than for metal which demonstrated values characteristic for hydrophobic materials. Histopathology showed a moderate inflammatory reaction after six weeks of the animal experiment. The reaction was least intense with T.S.M Acetal Dental. However, the inflammatory reaction contained eosinophils, just like in the case of Wironit extrahart, suggesting that both materials have allergic properties. Both materials produced morphological changes in the parotid glands of the animals. The adhesion of bacteria to the materials varied and depended on the bacterial strain. Staphylococcus aureus and Enterococcus hirae strains demonstrated the strongest adhesion to the mechanically polished chromium cobalt alloy. On the other hand, Escherichia coli adhered strongest to the acrylic resin (10 times the value for acetal resin). Pseudomonas aeruginosa revealed four-fold weaker adhesion to T.S.M. Acetal Dental than to other materials. The adhesion of Candida albicans to acetal resin was three times weaker than to acrylic resin. PMID- 22053629 TI - [The status of mineralized dental tissues in young competitive swimmers]. AB - INTRODUCTION: The aim of this study was to analyze the prevalence of caries and dental erosions in young competitive swimmers. MATERIAL AND METHODS: The study was done in 131 subjectively healthy persons. The study group consisted of 62 subjects--25 females and 37 males--who performed competitive swimming at the Szczecin House of Sports for a period 2-16 years. Each subject spent 16-25 hours per week in the swimming pool. The control group consisted of persons who attended randomly selected junior high schools in Szczecin and who performed recreational swimming or did not swim at all. The study and control groups were matched for gender, age, and educational level. RESULTS: Statistical analysis disclosed that dental lesions in the form of erosions were more common in competitive swimmers than in the control group. Dental erosions were located mainly on the labial surfaces of maxillary incisors. The intensity of caries was similar in both groups. PMID- 22053630 TI - [Early death in vascular surgery: an ongoing prognostic problem]. AB - INTRODUCTION: Prediction of complications in surgery is commonly done. There are conflicting reports concerning the usefulness of risk scales (P-POSSUM, APACHE, SAPS, ASA, Goldman, etc.) in vascular surgery. We decided to take a fresh look at preoperative risk factors of early death in the context of the usefulness of some parameters which have not been included in existing risk calculators. MATERIAL AND METHODS: The study group consisted of 1270 patients treated at the Department of Vascular Surgery, General Surgery, and Angiology, Pomeranian Medical University in Szczecin, during one year. METHOD This was a prospective non randomized study. All data recorded at admission and data from P-POSSUM, ASA, Goldman, and ECOG-Zubroda-WHO scales were analyzed. Statistics were done with discriminant, multivariate, and logistic tests. RESULTS: There were 42 early deaths in the group. The following independent risk factors were involved in early death: ASA > 2 (OR = 18.31), persistent atrial fibrillation (OR = 5.75), leukocytosis (OR = 13.31), glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 (OR = 5.78), systemic inflammatory response syndrome (SIRS) (OR = 11.36), emergency admission (OR = 38.62), critical limb ischemia (OR = 4.87), acute limb ischemia (OR = 8,98), abdominal aortic aneurysm (OR = 4.4), and ruptured aortic aneurysm (OR = 10.59). Logistic regression exposed the influence of five factors: ASA III, ASA IV, persistent atrial fibrillation, leukocytosis, GFR < 30 mL/kg/1.73 m2, and ruptured aortic aneurysm. The P-POSSUM calculator was found to be an accurate predictor of early death although the predicted death rate was insignificantly higher than the observed rate. CONCLUSION: Risk scales of early death currently used in vascular surgery need to be "refreshed". Creation of the Polish National Vascular Surgery Register seems to be unavoidable. PMID- 22053631 TI - Does Hynes-Anderson pyeloplasty improve renal function? AB - INTRODUCTION: With the advent of renoscintigraphy, improvement in renal function after Hynes-Anderson pyeloplasty became and continues to be an object of interest. We performed a retrospective analysis in a group of our patients with the hope of resolving some issues. MATERIAL: Medical files with complete renoscintigraphic data of 51 patients with symptomatic hydronephrosis who underwent Hynes-Anderson pyeloplasty between 1996 and 2002 were analyzed. Two study groups were formed: patients operated before the age of 12 months (n = 18, mean age 4 months), and patients operated after the age of 12 months (n = 33, mean age 8 years). METHODS: Renoscintigraphic imaging was performed using DTPA according to EANM guidelines. The following parameters were analyzed: differential renal function--DRF (%), glomerular filtration rate--GFR (mL/min), and type ofrenoscintigraphy (1--non-obstructive, 2--equivocal, 3--obstructive). Renoscintigraphy was done preoperatively, 3 and 12 months after surgery, and at the end of the follow-up. The level of significance was taken as p < or = 0.05. RESULTS: Preoperative DRF values in both groups (46 +/- 8 and 44 +/- 9) revealed no significant differences; GFR values (18 +/- 14 and 36 +/- 17) revealed significant differences (p < 0.001) between the groups. 55% of patients in each group had obstructive renoscintigraphy (2.3 +/- 0.9 and 2.2 +/- 0.9, respectively). Preoperative and consecutive postoperative DRF values did not reveal any significant differences. A progressive increase in GFR was noted in infants: the change was insignificant after three months from surgery, becoming significant after 12 months (p = 0.007), and reaching 45.6 +/- 7.1 (p = 0.02) at the end of follow-up. No significant differences were found in older children. Significant improvement in drainage noted three months after surgery in both groups (1.6 +/- 0.9; p = 0.008 and 1.4 +/- 0.8; p = 0.001) did not reveal any further change. CONCLUSIONS: 1. Hynes-Anderson pyeloplasty had no effect on DRF values in most patients regardless of age and initial renal function. 2. The increase in GFR in children operated before the first year of life seems attributable to the growth potential of the kidney, although surgery could have created conditions for full emergence of this potential. 3. Obstructive renoscintigraphy is not an unequivocal proof for clinically significant urine outflow obstruction; this can be demonstrated by clinical symptoms. PMID- 22053632 TI - A morphometric study of prenatal development of the human larynx. AB - INTRODUCTION: Precise knowledge of the anatomy and development of the airways in the fetus is needed for advances in neonatal medicine. The aim of this study was to assess the morphometry of the larynx during fetal development. MATERIAL AND METHODS: The study was performed on 47 human fetal larynges (27 male and 20 female) collected between the age of 13-27 weeks of intrauterine life according to Pineau and preserved in 10% buffered formalin. Five measurements of each larynx were performed: total height of the larynx, height of the anterior wall, height of the posterior wall of the larynx, sagittal diameter of the aperture of the larynx, and external sagittal diameter of the cricoid cartilage. Correlations between the results and crown-rump (C-R) length of human fetuses in relation to gender were analyzed. The percentage ratio of laryngeal length to C-R length in subsequent weeks of the fetal period and in relation to gender was determined. RESULTS: Dimensions of the larynx were found to correlate with crown-rump length. Mean lengths of the larynx were greater in male than in female fetuses at some stages of development. CONCLUSION: Ultrasound dimensions of the larynx are greater than dimensions found during postmortem examinations. PMID- 22053633 TI - [Assessment of the impact of some sociodemographic factors on the quality of life of patients with multiple sclerosis]. AB - INTRODUCTION: Multiple sclerosis is the most common cause of disability among young people, affecting the emotional and intellectual condition of the patient. Assessment of the quality of life enables long-term planning of the strategy of support and thus should constitute a permanent part of care for multiple sclerosis patients. The aim of this study was to assess the impact of gender, age, duration of the disease, and economic status of multiple sclerosis patients on the quality of life in separate domains. MATERIAL AND METHODS: A diagnostic survey was conducted in 64 patients with multiple sclerosis. We administered a questionnaire developed by us with questions referring to sociodemographic data of the patients. We also used the standard SF-36 questionnaire with eight scales. RESULTS: No significant differences between male and female SM patients were noted as regards the quality of life in each scale. Wealthy patients experienced a higher quality of life as regards the general health and physical functioning in comparison to patients with a middle economic status. There was no effect of the place of residence on the quality of life. Elderly patients and patients with long-term multiple sclerosis had a poorer quality of life in the physical functioning, general health, vitality, and role-emotional domains. CONCLUSIONS: 1. Gender and place of residence of multiple sclerosis patients has no effect on any of the scales of the quality of life. 2. High economic status favors a higher quality of life in the physical functioning and general health scales. 3. Age and long duration of multiple sclerosis are important factors decreasing the quality of life in most scales. PMID- 22053634 TI - [Physiotherapy and biological regeneration: for everyone?]. AB - Patients concerned with the quality of their lives direct their attention to biological regeneration centers. Visiting modern wellness and spa centers, they look for quick revitalization and improvement of physical fitness that will help them regain their strong professional performance. PMID- 22053635 TI - [The effectiveness of a comprehensive program of physiotherapy in shoulder pain syndromes]. AB - INTRODUCTION: Periarthritis humeroscapularis (PHS) is a disease notable for serious therapeutic problems arising from lesions in various tissue structures. The shoulder is the most important biokinematic element in the upper extremity. For this reason, physiotherapy continues to search for an ideal form of rehabilitation. Treatment of PHS is long and difficult. The correct diagnosis combined with physiotherapy can reduce the suffering of the patient and shorten the duration of the disease. Thus, the restoration of physical activity can be expedited. We decided to assess the effectiveness of a comprehensive program of physiotherapy in shoulder pain syndromes. The study was done at the Rehabilitation Unit of the Stablowice Clinic of the Wroclaw Health Center. We enrolled 30 patients aged 30 to 85 years (mean age: 60 +/- 14 years) with pain and limited mobility of the shoulder diagnosed as PHS. MATERIAL AND METHODS: A questionnaire with 12 questions addressing the intensity and extent of shoulder pain was prepared. Shoulder joint mobility was determined with a goniometric method. In addition, an 11-grade Numerical Rating Scale (NRS), where 0 meant no pain and 10 the most severe pain, was adopted. All patients underwent a series of 10 physiotherapeutic procedures directed at the shoulder joint. Assessment was made before and after therapy. RESULTS: A considerable reduction of pain was noted after physiotherapy and massage, while exercises significantly improved mobility, muscle status, and function of the upper extremity. CONCLUSIONS: The present study has shown that the comprehensive program of physiotherapy carried out at the Rehabilitation Unit of the Stablowice Clinic of the Wroclaw Health Center is effective in treating patients with the shoulder pain syndrome. PMID- 22053636 TI - [Introduction to LGBT: definitions, some historical facts, and evolution of thinking in the era of HIV/AIDS--hopes and challenges]. AB - This article deals with the subject matter of LGBT (lesbians, gays, bisexuals, transgenders), i.e. individuals who are not heterosexual, presenting definitions, some historical facts, and evolution of thinking in 2010. Attention is drawn to discrimination and stigmatization of members of the LGBT community. Problems related to the prevention of HIV/AIDS among men having sexual contacts with other men are discussed. A concise presentation of the functioning of the LGBT community in the heterosexual society is included. Emphasis is placed on equality of non-heterosexual orientations with reference to important ideas such as homo- and binormativity. PMID- 22053637 TI - [The Polish healthcare system: perspectives and possibilities for adoption of healthcare systems from other countries of the European Union]. AB - This work was undertaken to describe the basic elements of the Polish healthcare system and to examine possibilities for adoption of solutions existing in healthcare systems of other countries of the European Union. Healthcare systems were analyzed as to their model features and general directions of reform. Current problems, as well as attempts and concepts for reform of the Polish healthcare system were studied. Disadvantages and advantages of the Polish healthcare system are presented. The main disadvantages are: limited funding of medical services, monopoly of the National Health Fund (NFZ), lack of competition among insurers, unequal status of public versus private healthcare providers, indebtedness of public healthcare institutions, and limited access to healthcare. PMID- 22053638 TI - [Izydor Nahumowicz (1800-1842) and his work on the salt springs of Druskininkai]. AB - This article begins with a presentation of attractions of Druskininkai (formerly Druskieniki) in the first half of the 19th century. The life and scientific achievements of Izydor Nahumowicz (1800-1842), an eminent spa physician, are discussed. His treatise "Treatment with mineral waters in Druskininkai" (Grodno 1841) is presented in detail, as well as procedures preparing for treatment in Druskininkai with indications and contraindications for referring patients to this spa. Mention is made of the social life and entertainment in Druskininkai. PMID- 22053639 TI - The physician value modifier: pay-for-performance is coming to the physician fee schedule. PMID- 22053640 TI - A medical malpractice understanding to FASB ASU no. 2010-24. AB - FASB ASU No.2010-24, Healthcare Entities (Topic 954): Presentation of Insurance Claims and Related Insurance Recoveries changes how healthcare entities present medical malpractice liabilities on financial statements. Healthcare CFOs may need the assistance of their auditors and actuaries to ensure that ASU 2010-24 is appropriately implemented. Actuaries need to estimate the recoverable asset, using methods such as historical loss experience, increased limits factor, and commercial premium. PMID- 22053641 TI - Cutting hospital costs without cutting staff. AB - A hospital that is seeking ways to cut costs without compromising care should resist the temptation to lay off staff and instead make it a priority to improve efficiencies. This approach requires a formal program to identify and analyze all of the hospital's processes. The focus of the analysis should be to determine which activities are being performed efficiently, which are being performed inefficiently, and which are unnecessary. This effort will achieve the greatest success if it is customer-centric. PMID- 22053642 TI - Medicare bundled payment program: meaningful risk and limited reward. AB - CMS's Bundled Payments for Care Improvement initiative is accepting applications from healthcare provider organizations that would like to participate in the one of four alternative payment models under the initiative. Three of these models the All MS-DRG Hospital Model, the Global Hospitalization Model, and the Global Episode Model-target care delivered in an acute care setting. Hospitals contemplating participation in one of the models should weigh the benefits and risks of participation; it is likely the significant risk and limited financial benefit associated with the program will dissuade most providers from participating inthe initiative. PMID- 22053643 TI - David Blumenthal, MD: using information to drive value. Interview by Richard L Clarke. PMID- 22053644 TI - Medicare payment: how low it will go and how to prepare. AB - Hospitals should begin preparing now for a decade of reductions in Medicare payment with strategies aimed at: Partnering with clinical leadership, Performing detailed margin analysis, Engaging with service line managers and physicians, Revamping care coordination, Ensuring efficient operating room utilization, Improving emergency department operations. PMID- 22053645 TI - The financial implications of ACOs for providers. AB - To prepare for a future in which more and more patients will receive care in ambulatory settings, and acute care service capacity will likely need to be considerably downsized, hospitals should pursue five near-term strategies: Convert primary care practices to medical homes, Develop the IT capabilities required to manage and report on clinical and financial processes and outcomes, Integrate the clinical and financial interests with those of their physicians in improving value, Reduce cost per episode of care through bundled payment initiatives, Nurture key relationships with other providers. PMID- 22053646 TI - Dean Swindle: matching capital planning with strategic vision. PMID- 22053647 TI - Report data identify risk areas for improper payments. AB - Hospitals should take several steps in using data from the Program for Evaluating Payment Patterns Report (PEPPER) to enhance compliance efforts and identify risk areas for improper payments: Designate one person to monitor PEPPER releases and download the quarterly report. Review the reports and list all areas where the hospital is most at risk for improper payments. Prioritize at-risk areas with the national comparison, followed by jurisdictional and state comparison. Conduct small-sample case reviews in at-risk areas and determine next steps, such as process improvement or rebilling. Include hospital finance, compliance, legal, case management, and coding experts as part of discussion. PMID- 22053648 TI - Accountable clinical management: an integrated approach. AB - Hospitals should move from the traditional siloed approach to managing the clinical side of the enterprise, where finance leaders and clinicians play distinctly different roles without coordination, to an integrated approach that assembles a multidisciplinary team to focus coordinated attention on identifying and pursuing opportunities for clinical process improvement. Senior executives should lead this top-down effort to establish goals and set priorities for action, using an integrated, high-level reporting dashboard that shows overall performance in terms of quality, efficiency, and patient experience. Implementing integrated clinical management requires a clear, consistent communications plan and messaging for physicians and managers to show why it is increasingly necessary for both hospitals and physicians. PMID- 22053649 TI - Telling the data story the right way. AB - Effective data-driven analyses of service-line performance require: Buy-in and agreement at the outset from all parties (hospital and physicians) on the validity of the data used to evaluate service-line performance, Actionable data and metrics relevant to physicians, with financial goals tangibly linked to clinical improvement, Transparent sharing of data with physicians to build their trust and support the case for change, A physician champion who can help validate findings and guide how data are presented, Willingness of physicians to acknowledge that the opportunity for improved margin depends largely on the variable costs that they control as individuals. PMID- 22053650 TI - Preparing your organization's training program for ICD-10. AB - Training for ICD-10 is going to be expensive, though predictions of how expensive vary widely. Healthcare finance executives should create a flexible, multiyear capital and operating budget to prepare for ICD-10 conversion and the training and support that will be required. Healthcare organizations also should assess staff knowledge in the critical ICD-10 areas and begin training now to be ready for go-live by early 2013. PMID- 22053651 TI - Listening: executive skill most wanting? PMID- 22053652 TI - Meaningful tips for achieving meaningful use. PMID- 22053654 TI - Acute care and skilled nursing industry trends. PMID- 22053653 TI - What would you do? Is a merger the answer? PMID- 22053655 TI - Second-line chemotherapy for carboplatin/paclitaxel-refractory ovarian cancer: are multi-agent chemotherapies of little value truly? AB - PURPOSE: We examined whether second-line multi-agent chemotherapies are of any value for carboplatin/paclitaxel (TC)-refractory ovarian cancer. METHODS: Subjects included 60 patients with ovarian, peritoneal, or tubal carcinoma who received second-line platinum-based combination chemotherapy. Thirty-nine were treated with irinotecan/cisplatin or nedaplatin and 21 with docetaxel/cisplatin shortly after TC failure. Patients were divided between those who were refractory to initial platinum-based chemotherapy (n = 29, Group A) and those who were platinum-sensitive (n = 31, Group B). Efficacy and safety of the combination chemotherapies were compared between the two groups. RESULTS: Response to the combination chemotherapy was 10.3% in Group A and 41.9% in Group B. Median time to disease progression was 4.02 months and 7.21 months, respectively (p = 0.006), and median survival time was 7.89 months and 9.23 months, respectively (p = 0.003). There was no difference in response between the two regimens. Grade 3-4 hematologic toxicities were more frequent with the docetaxel regimen. CONCLUSION: The choice between agents for second-line chemotherapy for TC-refractory ovarian cancer should be based on whether the cancer was previously platinum-sensitive. With a history of such response, multi-agent chemotherapies are worth considering after TC failure. With no previous response, the expected efficacy of second-line multi-agent chemotherapy is low, suggesting the use of monochemotherapy. PMID- 22053656 TI - Robotic surgery for endometrial cancer: comparison of perioperative outcomes and recurrence with laparoscopy, vaginal/laparoscopy and laparotomy. AB - INTRODUCTION: Comparison of perioperative outcomes and recurrence in patients undergoing primary surgical treatment for endometrial cancer by robotics, laparoscopy, vaginal/laparoscopy, or laparotomy approaches. METHODS: Prospective analysis of 67 patients undergoing robotic surgery for endometrial cancer between March 2004 and December 2007. Comparison was made with similar patients operated between November 1999 and December 2006 by laparoscopy (37 cases), laparotomy (99 cases) and vaginal/laparoscopy approach (vaginal hysterectomy, bilateral adnexectomy/laparoscopic lymphadenectomy) (47 cases) and matched by age, body mass index (BMI), histological type and International Federation of Gynecologists and Obstetricians (FIGO) staging. RESULTS: Mean operating times for patients undergoing robotic, laparoscopy, vaginal/laparoscopy or laparotomy approach were 181.9, 189.5, 202.7 and 162.7 min, respectively (p = 0.006); mean blood loss was 141.4, 300.8, 300.0 and 472.6 ml, respectively (p <0.001); mean number of nodes was 24.7, 27.1, 28.6, and 30.9, respectively (p = 0.008); mean length of hospital stay was 1.9, 3.4, 3.5 and 5.6 days, respectively (p < 0.001). There were no significant differences in intra- or postoperative complications among the four groups. The conversion rate was 2.9% for robotics and 10.8% for the laparoscopy group (0.001). There were no differences relative to recurrence rates among the four groups: 9%, 14%, 11% and 15% for robotics, laparoscopy, vaginal/laparoscopy, and laparotomy, respectively. CONCLUSION: Robotics, laparoscopy and vaginal/laparoscopy techniques are preferable to laparotomy for suitable patients with endometrial cancer. Robotics is preferable to laparoscopy due to a shorter hospital stay and lower conversion rate and preferable to vaginal/laparoscopy due to a reduced hospitalization. PMID- 22053657 TI - Young adults awareness of HPV and vaccine acceptance after introduction of the HPV vaccine in the Dutch national vaccination program. AB - PURPOSE: To investigate the effect of implementation of the HPV vaccine on HPV knowledge and HPV vaccine acceptance. METHODS: From June until December 2009 in Nijmegen, the Netherlands, 698 male and female students aged 18-25 years were recruited and interviewed about HPV, cervical carcinoma and HPV vaccine acceptance. RESULTS: Of all participants 46.6% had never heard of HPV. Women and students from the medical faculty were significantly more aware of HPV. Acceptance of a "catch-up" HPV vaccination in women was 51% and in men 27%. Acceptance of the HPV vaccination for 12-year old girls was 79%. CONCLUSION: After implementation of the HPV vaccine in the national vaccination program, > 50% of the students lack knowledge on HPV. Acceptance of a "catch-up" HPV vaccination was low. However, the acceptance of HPV vaccination for 12-year-old girls was high. Vaccine implementation strategies, focusing on 12-16 year old girls, might have caused this difference. Young adults need to be informed that the HPV vaccine may still be efficient when they are sexually active, but HPV 16 and 18 negative. PMID- 22053658 TI - Total colectomy in primary ovarian cytoreduction. AB - OBJECTIVE: To review the indications, procedure, and complications associated with total colectomy with ileorectal anastamosis in women undergoing primary debulking of ovarian cancer. METHODS: Charts were reviewed to determine all patients undergoing total colectomy with ileorectal anastamosis during primary debulking of ovarian, peritoneal, or fallopian tube cancer. Charts were also reviewed for perioperative morbidity and mortality, as well as rates of fecal incontinence. RESULTS: Nine patients underwent the above procedures during primary debulking of ovarian cancer. The mean age was 61 years with a mean BMI of 31 kg/m2. The average postoperative hospital stay was 11 days with an average estimated blood loss of 700 ml. There was no perioperative mortality. Although all patients had greatly increased frequency of stools, no patients had incontinence of stool after eight weeks. CONCLUSIONS: Radical surgery, including total colectomy, can be performed in select patients with primary ovarian cancer. Acceptable morbidity, mortality, and rectal continence can be obtained. PMID- 22053659 TI - Association between Arg399Gln polymorphism of X-ray repair cross-complementing 1 (XRCC1) gene and sporadic endometrial cancer in the Polish population. AB - BACKGROUND: Endometrial cancer is one of the most common malignant neoplasms which appear in the uterine body. X-ray repair cross-complementing 1 (XRCC1) protein can be involved in the repair of DNA lesions, which are known to contribute to endometrial cancer. MATERIAL AND METHODS: The genotype analysis of XRCC1 Arg399Gln gene polymorphisms for 456 endometrial cancer patients and 300 controls of cancer-free subjects in the Polish population were performed using the PCR-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: The association between endometrial cancer occurrence and the Gln/Gln genotype of the Arg399Gln polymorphism (odds ratio, OR 2.28; 95% confidence interval, CI 2.02 2.54) was found. The Gln/Gln genotype of XRCC1 increased the risk of type I endometrial cancer occurrence (OR = 2.42, 95% CI = 2.12-2.72). No statistically significant association was found between gene polymorphisms and endometrial cancer risk factors such as BMI, HRT, uterine bleeding, endometrial ultrasound transvaginal, diabetes and hypertension. CONCLUSION: The results support the hypothesis that the Arg399Gln polymorphism of the XRCC1 gene may be associated with the incidence of sporadic endometrial cancer in Polish women. PMID- 22053660 TI - PTEN, tau-AP-3, thymidylate synthase immunohistochemistry scoring expression in patients with uterine leiomyomas, uterine smooth muscle tumors of uncertain malignancy potential and uterine leiomyosarcomas. AB - Uterine smooth muscle tumors are frequently classified as benign and malignant. However, an assortment of mitotic counts and nuclear atypia can be indecisive between uncertain malignant potential, and malignant uterine smooth muscle tumors. We applied three immunohistochemical parameters to distinguish between cases of benign, malignant, and those with uncertain malignant histology. PMID- 22053661 TI - Analysis of prognosis-related factors in patients with invasive cervical adenocarcinoma. AB - OBJECTIVE: To explore the prognostic related factors in patients with cervical adenocarcinoma. METHODS: Clinical and pathological data were retrospectively analyzed in 144 patients with cervical adenocarcinoma between 1995 and 2004. RESULTS: Five-year survival rates were 80.1%, 59.7%, 6.3 % and 0.0%, respectively, in patients with Stage I, II, III and IV cervical adenocarcinoma, and the overall 5-year survival rate was 59.0%. Univariate analysis indicated poor prognosis in non-exophytic tumor, tumor diameter > 4 cm, advanced clinical stage, mucinous adenocarcinoma and clear cell carcinoma, or poorly differentiated tumor. The prognosis was related to lymph node metastasis and deep myometrial invasion. Multivariate analysis indicated that besides clinical stage, myometrial invasion and lymph node metastasis, tumor shape was also an independent prognostic related factor. CONCLUSION: The prognosis is associated with tumor shape besides pre-confirmed clinical stage, myometrial invasion and lymph node metastasis. Ovarian preservation in young women remains to be further explored. PMID- 22053662 TI - Surgical management of invasive carcinoma of the vulva. A retrospective analysis and review. AB - PURPOSE: A retrospective study aiming to assess the survival rate, recurrence rate and complications of patients with invasive squamous cell carcinoma of the vulva. METHODS: 91 patients with invasive carcinoma of the vulva were included in the study. The following clinical factors were assessed: clinical stage, diameter of lesion, and degree of tumor differentiation. The Kaplan-Meier estimate for statistical analysis of survival was used. RESULTS: Surgery was primary treatment for 76 patients. The 5-year survival for FIGO Stage I was 93.3%, Stage II 85%, Stage III 51% and for Stage IV it was zero as estimated by the Kaplan-Meier test. Of the 52 women who underwent inguinal lymphadenectomy, 11 or 21.1% had positive nodes and four patients underwent pelvic node resection. Patients with tumor size < or = 2 cm had 16.7% positive inguinal nodes, while patients with tumor size > 2.1 cm had 29.4% of positive nodes. CONCLUSIONS: The right choice of surgical treatment after appropriate staging of the disease offers very good survival rates, while a more accurate assessment of the status of inguinal lymph nodes could reduce the extent of surgical treatment. PMID- 22053663 TI - Right colon laparoscopic resection with three-trocar access and associated gynecological procedures in patients with colorectal cancer and ovarian metastases. AB - BACKGROUND: Right laparoscopic colectomy was introduced to colorectal surgery later than the left colon procedure. Three-trocar laparoscopy has already been used successfully in the treatment of gynecological cancers. In the present study, we aimed to analyze the feasibility of performing an associated gynecological procedure following abdominal laparoscopic exploration and to evaluate the suitability of laparoscopic right colectomy for treating elderly patients. METHODS: We conducted a review of prospectively collected data on 100 consecutive patients who were treated with right laparoscopic colectomy using three trocars from January 2005 to April 2010. We recorded the patients' age (<70 or > 70 years), ASA status, body mass index (BMI), pain on postoperative days 1 and 2 (POD 1, 2), nodes retrieved, laparotomic conversion, mean operative time, time to intestinal recovery, and length of postoperative stay. RESULTS: All subjects were treated for cancer. Conversion to the laparotomic procedure was performed in 13/100, with no difference in terms of age. Operative time was longer for laparotomic conversion (p <0.05), with a longer postoperative stay. Elderly patients had higher ASA scores (p < 0.005); age did not influence the conversion rate or BMI status. Pain on POD 1 and 2 differed between the laparotomic and laparoscopic groups (p <0.0001). Associated procedures were performed in five subjects (3 oophorectomy and 2 cholecystectomy). CONCLUSIONS: Laparoscopy using the three-trocar technique is a safe procedure for treating colon cancer, including in elderly patients, and enables associated gynecological laparoscopic procedures to be performed. PMID- 22053664 TI - Immunohistochemical analysis of p16 expression in uterine smooth muscle tumors. AB - The expression of p16 as a tumor suppressor protein was evaluated in a retrospective analysis of paraffin-embedded tissue specimens of leiomyosarcoma (LMS), leiomyoma (LM) and normal myometrium. In this study, we investigated by immunohistochemistry p16 expression in 15 LMSs, 15 LMs and ten normal myometrium. Strong expression of p16 was found in 12 of the 15 LMSs and in three cases weak expression; three LMs had focal and weak p16 staining but none of the normal myometrium. A statistically significant difference regarding the frequency of p16 protein expression was observed between LMS and LM (p: 0.0001). We concluded that the results of this study confirm the overexpression of p16 in LMS. Therefore, the present study suggests that p16 might be a useful immunohistochemical marker which could help in distinguishing uterine LMS from LM and its benign variants. PMID- 22053666 TI - Trends in the incidence of uterine cancer in Niigata, Japan: a population-based study from 1982 to 2007. AB - This study investigated trends in the incidence of uterine cancer in Japan. Data from the Gynecological Cancer Registry of Niigata comprising all new cases of uterine cancer registered for the entire female population aged 15 years and over a 25-year period were examined. The age-standardized ratio of carcinoma in situ has substantially increased among females < 40 years of age (from 3.8 (in the period of 1982-1989) to 40.9 (2000-2007). There was a significant trend in increasing incidence of invasive cervical cancer for those < 40 years of age (from 4.7 to 13.1), whereas a significant trend of decreasing incidence for the 50+ year age group. The ratios of corpus cancer were increased approximately two folds both among the population aged < 50 years and those aged 50+ years and thus becoming equivalent to invasive cervical cancer. This prefecture-wide population based study shows the practical trend in uterine cancer in Japanese females. The current health service must emphasize education among young adults concerning cervical cancer prevention while concentrating on screening. Avoiding risk factors, such as obesity, and increasing protective factors may lower risk for corpus cancer both in younger and older females. PMID- 22053665 TI - The prognostic and predictive value of ERCC-1, p53, bcl-2 and bax in epithelial ovarian cancer. AB - AIM: To evaluate the expression of ERCC-1 in patients with epithelial ovarian cancer (EOC) and to correlate it with the expression of p53, bcl-2 and bax. MATERIALS AND METHODS: Tumor samples from 60 patients with EOC were immunohistochemically investigated for the expression of ERCC1, p53, bcl-2 and bax. RESULTS: ERCC-1 expression was significantly decreased in serous and endometrioid compared to clear cell carcinomas. P53 expression was significantly increased in serous compared to clear cell carcinomas. Bax expression was significantly increased in serous carcinomas as compared to MMTs. High disease stage was correlated with low ERCC-1 and high bcl-2 expression. ERCC-1 expression was associated with increased disease-free interval. CONCLUSION: ERCC-1 status seems to be correlated with disease-free interval, stage and tumor histologic subtype in patients with EOC. Nevertheless, our results indicate that single-gene expressions may be unreliable and thus caution is needed when used as potential prognostic or predictive markers. PMID- 22053667 TI - Prognostic significance of increased urinary neopterin concentrations in patients with breast carcinoma. AB - Increased serum or urinary concentrations of neopterin have been described in patients with tumors of different primary locations, but reports on neopterin in patients with breast carcinoma are relatively innumerous. We have evaluated urinary neopterin in 456 patients with breast carcinoma. Urinary neopterin was determined using high-performance liquid chromatography. Neopterin in patients was increased only in a minority of patients with breast carcinoma. Increased urinary neopterin was associated with inferior overall survival. Prognostic significance of increased urinary neopterin was evident in patients with tumors expressing hormone receptors or/and human epidermal growth factor receptor (HER) 2, but not in patients with triple negative tumors. Among other parameters determined, C-reactive protein, hemoglobin, peripheral blood neutrophil count and platelet count were significant prognostic factors. On multivariate analysis, age, expression of hormone receptors, neutrophils, stage and hemoglobin concentration were independent prognostic indicators. In conclusion, serum neopterin is increased only in a minority of patients with breast carcinoma. Increased urinary neopterin was predictive of poor survival in univariate, but not multivariate analysis. Age, expression of hormone receptors, neutrophils, stage and hemoglobin concentration were independent prognostic indicators. PMID- 22053668 TI - Loop electrosurgical excision procedure in Greek patients with vaginal intraepithelial neoplasia and history of cervical cancer. AB - OBJECTIVE: The aim of our study was to evaluate the therapeutic effectiveness of loop electrosurgical excision procedure (LEEP) in Greek patients with vaginal intraepithelial neoplasia (VAIN) and history of cervical cancer. MATERIALS AND METHODS: Between January 2002 and January 2009, eight women with histologically confirmed VAIN and history of cervical cancer were included in our study. For the LEEP procedure we used a high frequency Electrosurgery Unit with at least 80 W output. RESULTS: Complete response rate, at 12 months of follow-up, was 75%. Recurrence rate, at 12 months of follow-up, was 25%. Complete response rate, at 24 months of follow up, was 62.5%. Recurrence rate, at 24 months of follow up, was 37.5%. CONCLUSION: LEEP may constitute a valuable excisional method for the treatment of VAIN in cases with a history of cervical cancer. It provides an interpretable specimen of the whole lesion within a few minutes. It needs a short period of training and has low cost. PMID- 22053669 TI - Cervical conization--treatment for cervical intraepithelial neoplasia and carcinoma in situ. AB - PURPOSE: Cone biopsy is the best treatment for high-grade premalignant cervical changes. Cervical intraepithelial changes do not show any clinical picture until the process develops into carcinoma. METHOD: This retrospective study included 395 women who underwent conization at Gynecology and Obstetrics Clinic "Narodni front" during 2009. The chi-square test was used for comparing results. RESULTS: Pathohistological findings from biospy and conization were identical in 40.50% of patients, in 10.13%, the conization finding was more severe than the biopsy finding, while in 49.37% less severe than the biopsy finding. Resection margins status analysis showed that 12.66% of cones were positive. Comparison between cones with positive margins and operative techniques did not show any statistically significant difference; 64% of women with positive margins were over the age of 35. CONCLUSION: Operative conization techniques are equally represented. However in women over the age of 40 scalpel excision methods are recommended. In women over the age of 45 there is a statistically significant increase in the risk for positive resection margin with CIN3 and glandular lesions. PMID- 22053670 TI - Hormonal replacement therapy in ovarian cancer survivors: a survey among Greek gynecologists. AB - PURPOSE OF INVESTIGATION: In this survey we evaluated the prescription attitude of Greek gynecologists towards hormone replacement therapy (HRT) for ovarian cancer survivors. METHODS: An anonymous questionnaire was sent to 900 members of the Hellenic Society of Obstetrics and Gynecology presenting a hypothetical case of an ovarian cancer survivor with indications for HRT followed by a series of relevant questions. RESULTS: Two hundred and ninety-eight responses were analyzed with regards to age, gender and practice setting. HRT would be prescribed by 48% of Greek gynecologists; regarding type of regimen, 60% would prescribe tibolone, 19% estrogen alone and 21% estrogen plus progestagen. In contrast, 52% of Greek gynecologists would not prescribe HRT due to the fear of ovarian cancer relapse (83%), or the development of breast cancer (6%), or both cancers (9%); among them, 21% would alternatively prescribe CNS medications, 9% SERMs, phyto estrogens or bisphosphonates, while the remaining 70% would not prescribe anything. CONCLUSIONS: One out of two Greek gynecologists would prescribe HRT in ovarian cancer survivors. An alternative therapy, mainly CNS medications, would be suggested by 21% of the opposers. PMID- 22053671 TI - Activity of pegylated liposomal doxorubicin for extragenital mullerian adenosarcoma with sarcomatous overgrowth: a case report and a review of the literature. AB - A 47-year-old woman was diagnosed with extragenital mullerian adenosarcoma with sarcomatous overgrowth. One month after her initial surgery, the patient developed pelvic recurrence, which was completely excised by surgery. However, one month later, the patient developed further recurrences in her pelvis and upper abdomen. A clinical complete response was achieved with three cycles of liposomal doxorubicin and is currently clinically free of disease. So far, including the present case, 23 cases of extragenital mulleian adenosarcoma have been reported in the English literature. Because of the rarity of the reported cases, there are no treatment guidelines based on a good level of evidence. In the current report, through a literature review, we provide information on the activity of pegylated liposomal doxorubicin for extragenital mullerian adenosarcoma with sarcomatous overgrowth. PMID- 22053672 TI - An extremely rare presentation of relapse in endometrioid endometrial adenocarcinoma: isolated metastases to the tibia and humerus. Case report and review of the literature. AB - In endometrial carcinoma patients, metastases to bones are rare and isolated metastases to extremities are extremely rare. We describe the case of a 59-year old patient who underwent surgery followed by adjuvant radiotherapy due to endometrioid endometrial adenocarcinoma (grade 2, FIGO Stage II). After intervals of nine and 18 months respectively, she was diagnosed with metastatic tumours located in the right tibia and in the left humerus. The metastases were confirmed by biopsy. Following irradiation of metastatic lesions, the relief of symptoms was observed, and the patient remains under observation. We conclude that patients presenting a history of endometrial carcinoma with chronic pain in the extremities should be carefully evaluated, because although extremely rare, the carcinoma can metastasize to bones. Treatment of bone metastasis from endometrioid endometrial carcinoma by irradiation may increase quality of life and prolong survival. PMID- 22053673 TI - Myofibroblastic inflammatory breast tumor and fibrosarcoma: a case report. AB - Myofibroblastic inflammatory tumors can occur in any human tissue. They are benign lesions and more common in young patients. We describe the case of a 41 year-old patient with a nodule measuring 2.5 x 1.5 cm in the superior lateral quadrant of the left breast. The pathological examination showed proliferation of the spindle cells in dense fascicles interspersed by colagen among frequent plasmocytes, lymphocytes and eosinophils, associated with scarce typical mitosis. In the same site ten years before the patient had undergone a nodulectomy and the diagnosis was a benign filloid tumor. The patient returned with a nodule in the surgical scar at follow-up and the incisional biopsy showed a malignant filloid tumor with a sarcomatous component. A mastectomy was performed. PMID- 22053674 TI - A case of squamous cell carcinoma arising from endometriosis of the ovary. AB - Ovarian endometriosis sometimes develops into ovarian cancer, especially clear cell adenocarcinoma and endometrioid adenocarcinoma. However, endometriosis rarely develops into squamous cell carcinoma. We present a case of squamous cell carcinoma arising from endometriosis. A 47-year-old Japanese woman was given a diagnosis of ovarian squamous cell carcinoma arising from endometriosis. She was treated with combination chemotherapy consisting of paclitaxel and carboplatin once every three weeks. Four months after the initial chemotherapy, multiple liver tumors appeared, and her treatment was changed to palliative therapy. Based on this case, in which ovarian squamous cell carcinoma arose from endometriosis, endometriosis should be followed-up strictly. PMID- 22053675 TI - A rare ovarian Leydig cell tumor (hilar type) causing virilization in a postmenopausal woman. AB - All patients with virilization signs, increased levels of androgen hormones and rapidly progressive hirsutism should be evaluated for an androgen-producing tumor. The ovarian origin of virilization can be suspected by the presence of elevated levels of circulating androgens, with normal levels of cortisol metabolites and a negative dexamethasone suppression test. A case report of a 50 year-old postmenopausal patient with rapidly progressive hirsutism is presented. After an extensive preoperative investigation a right oophorectomy was performed and a Leydig-hilus cell tumor was diagnosed. PMID- 22053676 TI - Lobular carcinoma of the breast metastasizing to leiomyoma in a patient under letrozole treatment. AB - Metastasis of extragenital neoplasms to the uterus is extremely rare. Lobular breast cancers metastasize to the uterus more than ductal carcinomas, but they metastasize as tiny nodules that can be missed with the standard diagnostic workup. Uterine involvement by a metastatic tumor is usually a manifestation of end-stage disease; patients are reported to die within weeks to months. Therefore surgery is not recommended. Here we report a case of lobular breast cancer metastasizing to a leiomyoma in a patient using letrozole. Our patient was submitted to surgery because the leiomyoma had grown to the level of the xiphoid process. She is alive one year after the operation. In conclusion growth of leiomyomas under aromatase inhibitors should be considered as a sign of metastases and surgery can be planned in selected cases. PMID- 22053677 TI - Metastasis from endometrial carcinoma to bilateral breasts presenting as inflammatory breast lesions. AB - BACKGROUND: Endometrial carcinoma rarely metastasizes to the bilateral breasts and presents as an inflammatory breast lesion. In this paper, we report a case of bilateral breast metastatic endometrial carcinoma and describe the clinical and pathological features. It is the second case of this kind of disease and the first case report with full clinical data. CASE REPORT: A 56-year-old Chinese woman (G3, P3) with endometrial carcinoma received cytoreductive surgery and chemotherapy. Approximately 22 months later, she presented with pain in the right axillary region and edema of the right breast. The pathology report confirmed multifocal invasive papillary adenocarcinoma of the right mammary gland, consistent with endometrial carcinoma metastasis. Although she received many lines of chemotherapy, the disease still progressed and metastasized to the contralateral breast. Gefitinib (Iressa) improved symptoms temporarily. CONCLUSIONS: Bilateral breasts metastasis of endometrial carcinoma is rare and difficult to treat. Molecular targeted therapy may be an effective treatment for breast metastasis. PMID- 22053678 TI - Adenoid cystic carcinoma of the Bartholin's gland: case report and systematic review of the literature. AB - Adenoid cystic carcinoma (ACC) of the Bartholin's gland is a rare malignancy of the female genital tract. Seventy-nine cases have been reported in the literature. A 40-year-old women presented to our clinic with twice locally recurrent ACC of Bartholin's gland of the left vulva despite hemivulvectomy. Adjuvant radiotherapy was delivered after the third resection. There was no local recurrence after three years follow-up, although she developed lung metastases that remain under control with oral cyclophosphamide. Our case confirms the literature review, which indicates a slow growing tumor with frequent local recurrences (30%) and distant metastases (31%). Adjuvant radiotherapy and/or chemotherapy should be considered in the management of ACC of Bartholin's gland. PMID- 22053679 TI - Synchronous clear cell adenocarcinoma of the cervix and endometrioid carcinoma of the endometrium. AB - Synchronous primary malignant neoplasms of uterus are uncommon. Patients with synchronous cervical and endometrial cancers are even rarer. We describe a case of cervical clear cell carcinoma and endometrial adenocarcinoma occurring simultaneously in a 54-year-old woman presenting with intermittent vaginal bleeding. The concept of synchronous primary malignancies of the genital tract is also reviewed in this report. PMID- 22053680 TI - Proliferative Brenner tumor of the ovary. clinicopathological study of two cases and review of the literature. AB - BACKGROUND: Ovarian Brenner tumors are rare epithelial tumors that account for 1% 2% of all ovarian neoplasms. They can be subdivided into benign, borderline or proliferative, and malignant neoplasms. In the vast majority of cases, these lesions are benign. Tumors of borderline malignancy are less frequent and only about 1% of Brenner tumors are malignant. We present two cases of Brenner tumors with borderline malignancy which were treated in our Department together with a review of the literature. CASES: A 50-year-old, gravida 1, para 1, patient was admitted for abnormal vaginal bleeding. Clinical examination, abdominal ultrasound (US), and computed tomography (CT) revealed a cystic multilobulated tumor of the right ovary with solid elements measuring 20 x 19 x 15 cm in diameter. In the other case a 70-year-old, gravida 2, para 2, patient presented with severe urinary difficulties. Palpation revealed a mobile abdominopelvic tumor 10 x 15 in diameter. US and CT exhibited a cystic tumor with multiple solid elements and calcifications of the left ovary. Both patients underwent exploratory laparotomy. Total abdominal hysterectomy with bilateral salpingo oophorectomy and total omentectomy were performed in both cases, while pelvic lymphadenectomy was decided only in the second case. Histologically, in both cases the diagnosis confirmed borderline Brenner tumor. CONCLUSION: Although Brenner tumors are rare and the majority of them are benign, the correct histological diagnosis at frozen section with identification of the small proportion of malignant tumors, allows the extent of the operation to be adapted if needed. PMID- 22053681 TI - The application of a newly developed linear stapler preloaded with tissue reinforcement for distal pancreatectomy in the management of ovarian cancer. AB - Advanced ovarian cancer may extend into the spleen, and even the pancreatic tail, in which a splenectomy associated with distal pancreatectomy is crucial for optimal cytoreduction. A new linear stapler preloaded with tissue reinforcement is currently introduced. We herein report the first three cases of successful application of this device for distal pancreatectomy performed during cytoreductive surgery for ovarian cancer. PMID- 22053682 TI - Malignant melanoma ovarian metastasis mimicking acute tuboovarian abscess. AB - BACKGROUND: Metastases of malignant melanoma to the reproductive organs are occasionally encountered. They always represent a diagnostic challenge and they mimic various ovarian entities from primary ovarian malignancy to benign tumors. CASE: A 35-year-old woman presented with bilateral ovarian metastases which had clinical features of an acute state mimicking a tuboovarian abscess. The diagnosis was established postoperatively. CONCLUSION: Sophisticated imaging methods may be necessary in cases of ovarian tumors in patients with a previous history of melanoma with possible metastatic dissemination. Urgent admittance and treatment of these patients with a range of clinical symptoms can be critical and may lead to a wrong diagnosis. Attentive monitoring of ovarian morphology in women with treated malignant melanoma is mandatory to detect rare but possible metastatic sites. Regardless of surgical and adjuvant therapy dissemination of malignant melanoma to the ovary has unfortunately a poor prognosis. PMID- 22053683 TI - Isolated sigmoid colon metastasis from a primary fallopian tube carcinoma: a case report. AB - Isolated metastasis of primary fallopian tube carcinoma (PFTC) is extremely rare. We describe a case of a 41-year-old asymptomatic woman who was referred three years after the initial treatment for PFTC due to elevated sertum CA-125 levels. The abdominal and pelvic CT scans revealed a pelvic mass near the top of the vaginal vault. On surgery, a sigmoid colon tumour was found and a sigmoidectomy was performed. On histopathology the tumour involved the bowel wall from serosa to submucosa, without involvement of the underlying mucosa. Immunohistochemical staining was positive for cytokeratin 7 and negative for cytokeratin 20, and the tumour was determined to be a metastatic mullerian neoplasm, consistent with the initial PFTC. Although this is the first reported case of colon metastasis of PFTC, the possibility of such an unusual site of metastasis should be kept in mind, as PFTC may recur as isolated bowel lesions even in the absence of peritoneal disease. PMID- 22053684 TI - Primary carcinoma of the neovagina: a case report. AB - We present a case of squamous cell carcinoma arising in the neovagina of a woman in whom we performed vaginoplasty 20 years before. To the best of our knowledge, this is the 23rd case of total carcinoma arising in the neovagina constructed because of vaginal agenesis, and the 3nd case of carcinoma arising in the neovagina performed without using a graft. PMID- 22053685 TI - Uterine sarcoma with abdominal wall metastasis following laparoscopy: case report. AB - PURPOSE: This work aimed to prevent artificial implantation in laparoscopic surgery for gynecological tumors. METHODS: A case of uterine sarcoma with abdominal wall metastasis following laparoscopy was analyzed for clinical features. RESULTS: A diagnosis of uterine sarcoma was made in Stage IV and the previous laparoscopic surgery had caused artificial abdominal wall metastasis. CONCLUSIONS: We need to protect the puncture port in laparoscopic surgery of gynecological tumors to prevent artificial implantation. PMID- 22053686 TI - Gestational choriocarcinoma arising in a tubal ectopic pregnancy: case report. AB - OBJECTIVES: Gestational choriocarcinoma associated with ectopic pregnancy is an extremely rare event. Here we report one of these cases. CASE: A 38-year-old, gravida 4, parity 3, patient was admitted to the emergency room with the complaint of abdominal pain. Peritoneal irritation signs were present and serum hCG level was found to be greater than 15000 mUI/ml. Transvaginal ultrasound images were compatible with ruptured tubal ectopic pregnancy. Hemoperitoneum and ruptured tuba were found at laparatomy and a right salpingectomy was performed. The histopathological evaluation reported the lesion as primary tubal choriocarcinoma. The patient was referred to a tertiary care center for treatment and follow-up. CONCLUSION: Adequate monitoring of beta-hCG titers and careful examinations of pathologic specimens are important to avoid misdiagnosis of ectopic gestational trophoblastic disease. PMID- 22053687 TI - Rare metastases of carcinoma of uterine cervix. AB - This paper describes a case of cancer of the uterine cervix metastasizing in the spleen two years after the primary carcinoma was diagnosed and treated. After detailed diagnostics, the patient was subjected to surgery. Histopathological examination after splenectomy confirmed a very rare case - presence of metastases of planocellular carcinoma of the uterine cervix. Over the last ten years, references cite isolated cases of metastases of adenocarcinoma of the colon, stomach and breast in the spleen as well as lung carcinoma and malignant skin melanoma. Until now cases of uterine cervix carcinoma metastasizing to the spleen have been published as micrometastases detected in autopsy material. PMID- 22053688 TI - Angiokeratoma of the vulva. AB - Angiokeratoma of the vulva is relatively uncommon in the general population. We present two cases of angiokeratoma of the vulva and review the literature. The two patients presented with the complaint of vulvar pruritus. They underwent wide local excision of the lesions. Histopathology revealed angiokeratoma of the vulva. The women remain well with no evidence of recurrence 48 and 32 months after initial surgery. Although it is a rare disease, angiokeratoma of the vulva should be included in the differential diagnosis of a vulvar tumor. PMID- 22053689 TI - Advances in biomedical sciences. Preface. PMID- 22053690 TI - Recent advances in i-Gene tools and analysis: microarrays, next generation sequencing and mass spectrometry. AB - Recent advances in technology and associated methodology have made the current period one of the most exciting in molecular biology and medicine. Underlying these is an appreciation that modern research is driven by increasing large amounts of data being interpreted by interdisciplinary collaborative teams which are often geographically dispersed. The availability of cheap computing power, high speed informatics networks and high quality analysis software has been essential to this as has the application of modern quality assurance methodologies. In this review, we discuss the application of modern 'High Throughput' molecular biological technologies such as 'Microarrays' and 'Next Generation Sequencing' to scientific and biomedical research as we have observed. Furthermore in this review, we also offer some guidance that enables the reader as to understand certain features of these as well as new strategies and help them to apply these i-Gene tools in their endeavours successfully. Collectively, we term this 'i-Gene Analysis'. We also offer predictions as to the developments that are anticipated in the near and more distant future. PMID- 22053691 TI - Early growth response 1--a transcription factor in the crossfire of signal transduction cascades. AB - Early growth response-1 (Egr-1) is a Cys2-His2-type zinc-finger transcription factor. A broad range of extracellular stimuli is capable of activating Egr-1, thus mediating growth, proliferation, differentiation or apoptosis. Egr-1 is, therefore, participating in the progression of a variety of diseases such as atherosclerosis or cancer. Functional response elements connect Egr-1 to signal transduction cascades targeting Egr-1. Five serum response elements (SRE) have been identified in the promoter region of Egr-1, the binding region of serum response factor (SRF). The Rho/Rho-kinase pathway has been shown to regulate actin reorganization via LIM-kinase mediated cofilin phosphorylation. Recent studies have revealed that the actin binding striated muscle activator of Rho signaling (STARS) promotes translocation of myosin related transcription factors (MRTFs) into the nucleus, leading to SRF activation. The ternary complex factor (TCF) Elk-1 eventually bridges the gap between SRF-mediated gene transcription and the Raf/MEK/ERK pathway. Moreover, the Egr-1 promoter owns two cAMP response elements (CREs), whose relevance for gene expression is still unclear. An Egr-1 binding site (EBS) located on the Egr-1 promoter itself is arguing for a negative feedback mechanism. The acquired knowledge on transcriptional regulation of Egr-1 is not entirely understood. In this review, we highlight upstream and downstream signaling in vitro and in vivo associated with Egr-1. PMID- 22053692 TI - Molecular interaction between the glucocorticoid receptor and MAPK signaling pathway: a novel link in modulating the anti-inflammatory role of glucocorticoids. AB - Glucocorticoids (GCs) have a broad spectrum of life-sustaining functions and play an important role in health and diseases. At pharmacologic doses, GCs are potent immunosuppressive and anti-inflammatory agents. Inflammation and its related diseases present a huge ever increasing burden on the health and disease management. A plausible link of inflammation with aging, cardiovascular diseases and cancer makes matter even worst and calls for a better understanding to resolve the mechanisms associated with the cause and cure of inflammation. Understanding the physiological and molecular interlinks is an utmost importance in designing novel therapeutic strategies in combating inflammation. Advancement in research related to the mitogen-activated protein kinase (MAPK) signaling pathway and its regulation on inflammation has open up new and promising avenues in targeting inflammation as well as understanding the anti-inflammatory property of GCs. Molecular interaction between the ligand-activated glucocorticoid receptor (GR) and the MAPK signaling at different junctions inhibit the latter and thus may account for the anti-inflammatory role of GCs. Therapeutic application of GCs in combination with the recently added class of GR modulators having greater transrepresssion over transactivation (dissociative property) might overcome the clinical side effects associated with GCs. PMID- 22053693 TI - HSP70 expression and its role in preeclamptic stress. AB - Preeclampsia, a hypertensive pregnancy-specific disorder, has long been analyzed for its association with cellular stress. It still remains one of the most serious complications of pregnancy. It is a multi-system disorder that affects maternal vascular function and fetal growth. The physiopathology of preeclampsia is still unclear, but an imbalance between reactive oxygen species (ROS) and antioxidants, appears to be an important contributing factor. Oxidative stress has been increasingly postulated as a major contributor to endothelial dysfunction in preeclampsia (PE). The ROS promotes lipid oxidation and are known to induce stress proteins, such as hemeoxygenase 1 (HO-1) and heat-shock protein 70 (HSP70). Embryonic and placental cells are highly sensitive to oxidative stress due to their proliferate nature. Endothelial cell dysfunction is suggested to be a part of wider maternal inflammatory reaction responsible for the clinical syndrome of preeclampsia. Part of the dysfunction in endothelial cell and trophoblast is attributed to oxidative stress developed during pregnancy. The disequilibrium in compensatory antioxidant control is proposed as a causative mechanism in the pathophysiology of preeclampsia. HSP70 acts as the secondary line of defense in systems with compromised antioxidant function. This article reviews the differential expression of HSP70 and the effect of mint-tea therapy to modulate preeclamptic oxidative damage. PMID- 22053694 TI - High-throughput screening assays for cyclooxygenase-2 and 5-lipoxygenase, the targets for inflammatory disorders. AB - High-throughput screening (HTS) involves testing of compound libraries against validated drug targets using quantitative bioassays to identify 'hit' molecules that modulate the activity of target, which forms the starting point of a drug discovery effort. Eicosanoids formed via cyclooxygenase (COX) and lipoxygenase (LOX) pathways are major players in various inflammatory disorders. As the conventional non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit both the constitutive (COX-1) and the inducible (COX-2) isoforms have gastric and renal side effects and the recently developed COX-2 selective anti-inflammatory drugs (COXIBs) have cardiac side effects, efforts are being made to develop more potent and safer antiinflammatory drugs. Current assay methods for these enzymes, such as oxygraphic, radioisotopic, spectrophotometric etc. are not compatible for screening of large number of compounds as in drug discovery programs. In the present study, HTS-compatible assays for COX-1, COX-2 and 5-LOX were developed for screening of compound libraries with the view to identify potential anti inflammatory drug candidates. A spectrophotometric assay involving co-oxidation of tetramethyl-p-phenylene diamine (TMPD) during the reduction of prostaglandin G2 (PGG2) to PGH2 was adopted and standardized for screening of compounds against COX-1 and COX-2. Similarly, the HTS-compatible FOX (ferrous oxidation-xylenol orange) based spectrophotometric assay involving the formation of Fe3+/xylenol orange complex showing absorption in the visible range was developed for screening of compounds against 5-LOX. PMID- 22053695 TI - Transforming growth factor-beta 1 induces angiogenesis in vitro via VEGF production in human airway smooth muscle cells. AB - Increase in size and number of bronchial blood vessels as well as hyperaemia are factors that contribute to airway wall remodelling in patients with chronic airway diseases, such as asthma and chronic obstructive pulmonary diseases (COPD). Expression of transforming growth factor beta 1 (TGF-beta 1), a multifunctional cytokine as well as vascular endothelial growth factor (VEGF), a key angiogenic molecule, has been shown in the inflammed airways in patients with chronic airway diseases. TGF-beta 1 has been implicated in the regulation of extracellular matrix, leading to airway remodelling in patients with chronic airway diseases. However, the role of TGF-beta 1 in regulating VEGF expression in patients with chronic airway diseases, as well as the underlying mechanisms are not yet well established. We investigated whether TGF-beta 1 stimulates VEGF expression in vitro and hence could influence vascular remodelling. Cultured human airway smooth muscle cells (HASMC) were serum deprived for 60 h before incubation with 5ng/ml of TGF-beta 1 for different time points. Control cells received serum-free culture medium. TGF-beta 1 treatment resulted in time dependent HASMC cell proliferation with maximal values for DNA biosynthesis at 24 h and cell number at 48 h. Northern blot analysis of VEGF mRNA expression showed increased levels in cells treated with TGF-beta 1 for 4 to 8 h. TGF-beta 1 also induced a time-dependent release of VEGF proteins in the conditioned medium after 48 h of treatment. Furthermore, the ability of HASMC-released VEGF proteins to induce human umbilical vein endothelial cells proliferation was inhibited by VEGF receptor antagonist, confirming that TGF-beta 1 induced VEGF was biologically active. We conclude that TGF-beta 1 in addition to an extracellular matrix regulator also could play a key role in bronchial angiogenesis and vascular remodelling via VEGF pathway in asthma. PMID- 22053696 TI - Involvement of neuronal NO synthase in collateral artery growth. AB - To evaluate the role of neuronal nitric oxides synthase (nNOS) in collateral artery growth (arteriogenesis), we analyzed the expression pattern of nNOS at distinct time points on RNA and protein levels in a rabbit and a murine model of peripheral arteriogenesis. In the rabbit model, Northern blot analyses revealed a significant upregulation of nNOS at 6 h (1.6-fold), 12 h (2.2-fold) and 24 h (2.0 fold) after induction of arteriogenesis via femoral artery ligation, when compared to the sham operated side. In mice, an upregulation of nNOS was also detected using Northern blot (at 6 h, 12 h) and qRT-PCR (12 h: 2.4-fold). On the protein level, nNOS was found to be upregulated 24 h after femoral artery ligation. Immunohistochemical staining showed that nNOS was localized in endothelial and smooth muscle cells of collateral arteries, as well as in skeletal muscle and nerves. In summary, our data provide evidence that nNOS is not constitutively expressed, but is induced during arteriogenesis, playing a role in supplying reactive oxygen species such as H2O2 and low levels of NO. PMID- 22053697 TI - Free radical reactions of a naturally occurring flavone baicalein and possible mechanisms towards its membrane protective properties. AB - Baicalein (5, 6, 7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a naturally occurring flavone present in some of the medicinal plants is known for its potential therapeutic effects, such as cardioprotective, anticancer and anti inflammatory properties. However, detailed role and mechanisms behind its protective properties against different generators for oxidative stress have not been examined. In the present study, we investigated the possible protective ability of baicalein against the membrane damage caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the mechanisms involved using pulse radiolysis technique. Baicalein offered efficient protection even at a concentration of 10 microM towards membrane damage caused by lipid peroxidation induced by the gamma-radiation, peroxyl radicals, ascorbate-Fe2+ and peroxynitrite in rat liver mitochondria and heart homogenate. To elucidate its reaction mechanisms with biologically relevant radicals, transient absorption spectroscopy employing pulse radiolysis technique was used. Baicalein showed fairly high rate constants (3.7 x 10(9), 1.3 x 10(9) and 8.0 x 10(8) dm3 mol(-1) s(-1) for hydroxyl, azidyl and alkylchloroperoxyl radicals, respectively), suggesting that baicalein can act as an effective scavenger of these radicals. In each case, the phenoxyl radical of baicalein was generated. Thus, it was evident that the phenolic moiety of baicalein was responsible for the free radical scavenging process. Baicalein also reacts with linoleic acid peroxyl radical (LOO*), indicating its ability to act as a chain breaking antioxidant. Peroxynitrite-mediated radicals were shown to be reactive towards baicalein and the bimolecular rate constants were 2.5 x 10(7) and 3 x 10(8) dm3 mol(-1) s(-1) for *NO2 and CO3*(-) radicals, respectively. In conclusion, our results revealed the potential of baicalein in protecting mitochondrial membrane against oxidative damage induced by the four different agents. We propose that the protective effect is mediated via scavenging of primary and secondary radicals generated during oxidative stress. PMID- 22053698 TI - Modulatory effect of plasma folate and polymorphisms in one-carbon metabolism on catecholamine methyltransferase (COMT) H108L associated oxidative DNA damage and breast cancer risk. AB - The present study was aimed to investigate the modulatory role of plasma folate and eight putatively functional polymorphisms of one-carbon metabolism on catecholamine methyltransferase (COMT)-mediated oxidative DNA damage and breast cancer risk. Plasma folate and 8-oxo-2'-deoxyguanosine (8-oxodG) were estimated by commercially available kits, while polymorphisms were screened by PCR-RFLP and PCR-AFLP methods. COMT H108L polymorphism showed independent association with breast cancer (OR: 1.73, 95% CI: 1.31-2.30). No significant interaction was observed between folate status and COMT genotype. Multifactor dimensionality reduction (MDR) analysis gave evidence for the significant epistatic (gene-gene) interactions (p<0.0001) of COMT H108L with reduced folate carrier 1 (RFC1) G80A, thymidylate synthase (TYMS) 5'-UTR 3R2R, TYMS 3'-UTR ins6/de16. Increased plasma 8-oxodG were observed in cases compared to controls (mean +/- SE: 5.59 +/- 0.60 vs. 3.50 +/- 0.40 ng/ml, p<0.004). Plasma folate deficiency alone was not a significant predictor of 8-oxodG elevation. The genotype combinations namely, RFC1 G80A/methionine synthase reductase (MTRR) A66G, RFC1 G80A/SHMT C1420T/TYMS 3R2R and serine hydroxymethyltransferase (SHMT) C1420T/TYMS 3R2R/methionine synthase (MTR) A2756G/COMT H108L were strong predictors of 8-oxodG elevation in the order of risk. To conclude, the current study provides substantial evidence for a cross talk between one-carbon metabolism and COMT catalysis that might influence oxidative DNA damage and breast cancer risk. PMID- 22053699 TI - Preferential recognition of methylglyoxal-modified calf thymus DNA by circulating antibodies in cancer patients. AB - Methylglyoxal (MG) has been implicated in mutagenesis and cancer. Present study probes the antigenicity of MG damaged DNA in cancer patients. Purified calf thymus DNA was damaged by the synergistic action of MG, lysine (Lys) and CuSO4 for 24 h at 37 degrees C. DNA modifications produced single-strand breaks, hyperchromicity in UV spectrum and increased fluorescence intensity. Binding characteristics of auto-antibodies in cancer patients were assessed by direct binding and inhibition ELISA. These antibodies exhibited enhanced binding with the modified DNA, as compared to the native form. The effect was more pronounced when affinity-purified IgG was used in place of the serum. In conclusion, MG modified DNA presents unique epitopes which are recognized as non-self by the immune system and may, therefore, be one of the factors for the autoantibody induction in cancer patients. PMID- 22053700 TI - Six-year experience of permanent prostate brachytherapy for clinically localized prostate cancer. AB - This report presents the outcome of prostate permanent brachytherapy (PPB). One hundred and seventy-two patients with clinically localized prostate cancer were treated with permanent brachytherapy using iodine-125 seeds (125-I) at Hiroshima University Hospital from July 2004 to June 2010. This study evaluated the efficacy of PPB in these patients. The median patient age was 69 years (range 53 to 82 years), the median prostate-specific antigen (PSA) value before biopsy was 6.75 ng/ml (range 3.5 to 47.9 ng/ml), and the median prostate volume was 23.1 ml (range 10.1 to 57 ml). The median follow-up was 37 months (range 1 to 72 months). The serum PSA levels decreased continuously after PPB throughout the entire follow-up period in 97% of patients without neoadjuvant hormonal therapy. No relapse occurred during the follow-up period in patients at low risk. Our 6-year experience suggests that PPB is effective for localized prostate cancer. Patients with prostate cancer that does not require combined external beam radiation therapy (EBRT) have the best chance of responding to treatment. PMID- 22053701 TI - Relationship between 3-O-methyldopa and the clinical effects of entacapone in advanced Parkinson's disease. AB - The aim of this study is to clarify the relationship between serum 3-O-methyldopa (3-OMD) and the clinical effects of entacapone. The 3-OMD and maximum serum concentration (Cmax) of levodopa were measured in 21 Parkinson's Disease patients who took 100 mg levodopa / dopa decarboxylase inhibitor. After the administration of entacapone, the 3-OMD concentration and percentage of "on" time during waking hours (% of "on" time) were studied for 8 weeks. The 3-OMD concentration was reduced by 34%, and the increase in % of "on" time was 28% at the 8th week compared with baseline. We defined the COMT-index as [baseline 3-OMD concentration] / [levodopa Cmax when 100 mg levodopa was administered alone]. The COMT-index was significantly correlated with the increase in % of "on" time at the 8th week. In conclusion, the measurement of baseline 3-OMD and levodopa pharmacokinetics is useful for predicting the clinical effects of entacapone. PMID- 22053702 TI - Detection of large expansions in SCA8 using a fluorescent repeat-primed PCR assay. AB - Spinocerebellar ataxia type 8 (SCA8) is a neurodegenerative disorder characterized by slowly progressive cerebellar ataxia. It is caused by bidirectional expression of (CUG)n expansion in the ATXN80S/ATXN8 gene and (CAG)n expansion transcripts in ATXN8. The diagnosis of SCA8 must be confirmed by the presence of a (CTG)n trinucleotide repeat expansion in the ATXN8OS gene. On the other hand, there are many human genetic diseases that are caused by expansion of short tandem repeats. Since Werner et al proposed a repeat-primed fluorescent PCR to detect large CTG-repeats in myotonic dystrophy, Friedreich ataxia, SCA2, SCA7, SCA10 and SCA12 have been reported. In this study, we applied a fluorescent PCR method for detection of expanded repeats in the ATXN8OS/ATXN8 gene. Although this test cannot give a precise estimate of the size of the expansion, it proved useful for confirming the presence of expansions in SCA8. PMID- 22053703 TI - A case of idiopathic intracranial hypertension related with vesicoureteral reflux. AB - Pseudotumor cerebri is idiopathic intracranial hypertension. The etiology of this syndrome has not been fully clarified. Excess cerebrospinal fluid production, scarcity of cerebrospinal fluid absorption, intracranial venous pressure elevation, increased intracranial blood volume are all thought to be responsible. The symptoms of the disease may be ordered according to prevalence as follows: headache due to increased intracranial pressure, blurred vision and diplopia. A thirteen-year-old female patient was brought in with complaints of headache, double and blurred vision. Systemic arterial hypertension (140/70 mmHg) was determined. Vesicoureteral reflux was detected as the hypertension etiology. In this article a rare pseudotumor cerebri case is presented secondary to vesicoureteral reflux which caused hypertension. PMID- 22053704 TI - Synthesis, characterization, and materials chemistry of Group 4 silylimides. AB - This paper focuses on the development of potential single source precursors for M N-Si (M = Ti, Zr or Hf) thin films. The titanium, zirconium, and hafnium silylimides (Me(2)N)(2)MNSiR(1)R(2)R(3) [R(1) = R(2) = R(3) = Ph, M = Ti(1), Zr (2), Hf (3); R(1) = R(2) = R(3) = Et, M = Ti (4), Zr (5), Hf (6); R(1) = R(2) = Me, R(3) = (t)Bu, M = Ti (7), Zr (8), Hf (9); R(1) = R(2) = R(3) = NMe(2), M = Ti (10), Zr (11), Hf (12)] have been synthesized by the reaction of M(NMe(2))(4) and R(3)R(2)R(1)SiNH(2). All compounds are notably sensitive to air and moisture. Compounds 1, 2, 4, and 7-10 have been structurally characterized, and all are dimeric, with the general formula [M(NMe(2))(2)(MU-NSiR(3))](2), in which the MU(2)-NSiR(3) groups bridges two four-coordinate metal centers. The hafnium compound 3 possesses the same basic dimeric structure but shows additional incorporation of liberated HNMe(2) bonded to one metal. Compounds 11 and 12 are also both dimeric but also incorporate additional MU(2)-NMe(2) groups, which bridge Si and either Zr or Hf metal centers in the solid state. The Zr and Hf metal centers are both five-coordinated in these species. Aerosol-assisted CVD (AA-CVD) using 4-7 and 9-12 as precursors generates amorphous films containing M, N, Si, C, and O; the films are dominated by MO(2) with smaller contributions from MN, MC and MSiON based on XPS binding energies. PMID- 22053705 TI - Induction of arginine vasopressin-enhanced green fluorescent protein expression in the locus coeruleus following kainic acid-induced seizures in rats. AB - Seizure causes autonomic, neuroendocrine and stress responses. We examined the effects of kainic acid (KA)-induced seizures on the expression of the arginine vasopressin (AVP)-enhanced green fluorescent protein (eGFP) in the locus coeruleus (LC), an area known to contain noradrenergic cells, in AVP-eGFP transgenic male and female rats, with the rationale to identify stressors which induce AVP synthesis in the LC. Subcutaneous (s.c.) administration of KA caused a progressive development of seizure behavior within 24 h. AVP-eGFP fluorescence in the LC was detected 6, 24, and 48 h and 1 week after administration of KA (12 mg/kg). From a nearly undetectable level, it reached a maximum at 48 h after s.c. administration of KA and returned to the basal levels after 2 weeks. AVP-eGFP fluorescence in the LC after s.c. administration of KA was significantly reduced by the pretreatment with MK-801 (nonselective N-methyl-D-aspartate (NMDA) receptor antagonist). In the KA-administered rats, immunohistochemistry for tyrosine hydroxylase (TH) revealed that the eGFP fluorescence was co-localized with TH-immuno-reactivity in the LC. These results suggest that the synthesis of AVP-eGFP is potentially up-regulated in noradrenergic neurons in the LC after KA induced seizures through the activation of NMDA receptors. PMID- 22053706 TI - Chemical characterization of Sacha Inchi (Plukenetia volubilis L.) oil. AB - A chemical characterization of the major components, namely, triacylglycerols (TAGs), polyphenols, and tocopherols in a Sacha inchi oil derived from cold pressing of the seed, is hereby reported. To tackle such a task, high-performance liquid chromatography in combination with photodiode array (PDA), fluorescence (RF), and mass spectrometry (MS) detection was employed. The latter was interfaced with atmospheric pressure chemical ionization and with electrospray ionization for the analysis of TAGs and polyphenols, respectively, whereas RF detection was tested for the determination of tocopherol content. Furthermore, fatty acid methyl esters (FAMEs) were evaluated by gas chromatography-flame ionization detector. A 93% amount of total fatty acids was represented by unsaturated FAMEs with the greatest percentage represented by linoleic (L) and linolenic (Ln) accounting for approximately 50 and 36%, respectively. The main TAGs (>10%) were represented by LLnL, LnLnLn, and LnLLn; the latter was present in the oil sample at the highest percentage (22.2%). Among tocopherols, gamma tocopherol was detected to be the most abundant component (over 50%). The polyphenolic composition was also investigated, and a total of 15 compounds were positively identified, through the complementary analytical information coming from PDA and MS data. To the best of our knowledge, this is the first report providing a thorough chemical characterization of a Plukenetia volubilis L. oil. PMID- 22053707 TI - Laparoscopic assessment of a migrated ventriculoperitoneal shunt into an inguinal hernia. AB - Placement of a ventriculoperitoneal (VP) shunt may increase intraabdominal pressure and lead to an abdominal or genitourinary complication. We report on a 2 month-old boy with complex congenital neurologic and cardiac anomalies who had a VP shunt migrate into the left inguinal hernia. This report demonstrates how a laparoscopic approach can be successfully used to reposition the VP shunt, identify a contralateral inguinal hernia, and repair both without any additional incisions. PMID- 22053708 TI - A cell-compatible conductive film from a carbon nanotube network adsorbed on poly L-lysine. AB - Single-walled carbon nanotubes (SWNTs) have shown promise for use in organic electronic applications including thin film transistors, conducting electrodes, and biosensors. Additionally, previous studies found applications for SWNTs in bioelectronic devices, including drug delivery carriers and scaffolds for tissue engineering. There is a current need to rapidly process SWNTs from solution phase to substrates in order to produce device structures that are also biocompatible. Studies have shown the use of surfaces covalently functionalized with primary amines to selectively adsorb semiconducting SWNTs. Here we report the potential of substrates modified with physisorbed polymers as a rapid biomaterials-based approach for the formation of SWNT networks. We hypothesized that rapid surface modification could be accomplished by adsorption of poly-L-lysine (PLL), which is also frequently used in biological applications. We detail a rapid and facile method for depositing SWNTs onto various substrate materials using the amine-rich PLL. Dispersions of SWNTs of different chiralities suspended in N methylpyrrolidinone (NMP) were spin coated onto various PLL-treated substrates. SWNT adsorption and alignment were characterized by atomic force microscopy (AFM) while electrical properties of the network were characterized by 2-terminal resistance measurements. Additionally, we investigated the relative chirality of the SWNT networks by micro-Raman spectroscopy. The SWNT surface density was strongly dependent upon the adsorbed concentration of PLL on the surface. SWNT adsorbed on PLL-treated substrates exhibited enhanced biocompatibility compared to SWNT networks fabricated using alternative methods such as drop casting. These results suggest that PLL films can promote formation of biocompatible SWNT networks for potential biomedical applications. PMID- 22053709 TI - Hydrogels as intracellular depots for drug delivery. AB - The intracellular activity and drug depot characteristics of micrometer-sized hydrogels are described. The hydrogel structure is formed after cellular uptake of a solid polymeric nanoparticle that swells in response to mildly acidic conditions as it transforms from a hydrophobic to a hydrophilic structure. These nanoparticles are rapidly taken up into A549 human non-small cell lung cancer cells with 88.3 +/- 0.8% of cells experiencing uptake in 24 h, undergo expansion to release encapsulated drug and can effectively deliver chemotherapeutics in vitro. The anticancer drug paclitaxel was also shown to have a 3- to 4-fold increased affinity for the expanded nanoparticle state, allowing the expansile nanoparticles to act as intracellular drug depots and concentrate the drug locally. PMID- 22053710 TI - Tumor necrosis factor-alpha and receptor activator of nuclear factor-kappaB ligand augment human macrophage foam-cell destruction of extracellular matrix through protease-mediated processes. AB - By secreting proteases such as cathepsins and matrix metalloproteinases (MMPs), macrophage foam cells may be a major cause of ruptured atherosclerotic plaques. The aims of the present study were to investigate in vitro role of human macrophage foam cells in degrading type I collagen, a major component of extracellular matrix (ECM) in plaques, and to establish whether the pro inflammatory molecules, tumor necrosis factor (TNF)-alpha, and receptor activator of nuclear factor-kappaB ligand (RANK-L) increase this degradation. CD14+ monocytes isolated from peripheral blood were differentiated into macrophage foam cells and cultured on a type I collagen matrix in the presence of TNF-alpha and RANK-L. Matrix degradation was measured by the cathepsin K-generated C-terminal cross-linked telopeptide of type I collagen (CTX-I) and the MMP-generated carboxyterminal telopeptide of type I collagen (ICTP) in supernatants showing that macrophage foam cells secrete MMPs and cathepsin K, resulting in release of ICTP and CTX-I. Stimulation with TNF-alpha increased CTX-I and ICTP dose dependently, with ICTP levels increasing by 59% and CTX-I levels increasing by 43%. RANK-L enhanced the release of CTX-I and ICTP by 56% and 72%, respectively. This is, to our knowledge, the first data describing a simple in vitro system in which macrophage foam cells degradation of matrix proteins can be monitored. This degradation can be enhanced by cytokines since TNF-alpha and RANK-L significantly increased the matrix degradation. This in vitro system in part is a model system for the macrophage-mediated proteolytic degradation of the ECM, which is found in many diseases with an inflammatory component. PMID- 22053712 TI - In vitro evaluation of the schistosomicidal potential of Eremanthus erythropappus (DC) McLeisch (Asteraceae) extracts. AB - Eremanthus erythropappus (DC) McLeisch, a plant popularly known as Candeia (Asteraceae), has high therapeutic potential. In this study, the in vitro schistosomicidal potentials of the ethanolic, dichloromethane and hexane extract of branches were evaluated. Couples of worms obtained from the infected mice were cultured in RPMI supplemented with foetal bovine serum and antibiotics. Four pairs of adult worms were exposed to increasing concentrations of each extract and examined by light microscope. The extracts at 100 and 200 ug mL(-1) had schistosomicidal activity, as demonstrated by the analysis of several aspects such as tegument darkening, absence of motility, incapacity of adhesion in culture plate and absence of egg in culture medium. At 50 and 75 ug mL(-1), the dichloromethane and hexane extracts were highly effective. The results suggest that these extracts could be useful in the development of new schistosomicidal drugs. PMID- 22053711 TI - Assessment of compound hepatotoxicity using human plateable cryopreserved hepatocytes in a 1536-well-plate format. AB - Hepatotoxicity is a major concern for both drug development and toxicological evaluation of environmental chemicals. The assessment of compound-induced hepatotoxicity has traditionally relied on in vivo testing; however, it is being replaced by human in vitro models due to an emphasis on the reduction of animal testing and species-specific differences. Since most cell lines and hybridomas lack the full complement of enzymes at physiological levels found in the liver, primary hepatocytes are the gold standard to study liver toxicities in vitro due to the retention of most of their in vivo activities. Here, we optimized a cell viability assay using plateable cryopreserved human hepatocytes in a 1536-well plate format. The assay was validated by deriving inhibitory concentration at 50% values for 12 known compounds, including tamoxifen, staurosporine, and phenylmercuric acetate, with regard to hepatotoxicity and general cytotoxicity using multiple hepatocyte donors. The assay performed well, and the cytotoxicity of these compounds was confirmed in comparison to HepG2 cells. This is the first study to report the reliability of using plateable cryopreserved human hepatocytes for cytotoxicity studies in a 1536-well-plate format. These results suggest that plateable cryopreserved human hepatocytes can be scaled up for screening a large compound library and may be amenable to other hepatocytic assays such as metabolic or drug safety studies. PMID- 22053713 TI - Application of groEL gene for the species-specific detection of Vibrio parahaemolyticus by PCR. AB - AIMS: Vibrio parahaemolyticus is a significant cause of human gastrointestinal disorders and is transmitted through ingestion of raw or undercooked contaminated seafood. We used the groEL gene for the species-specific detection of V. parahaemolyticus from artificially inoculated shellfish, fish and seawater. METHODS AND RESULTS: The nucleotide sequences of 24 Vibrio and seven non-Vibrio spp. were compared, and less conserved regions were selected for the designing of primer sets. To detect V. parahaemolyticus specifically, PCR conditions were standardized and tested to evaluate the specificity of primers. A 510-bp band was appeared only from V. parahaemolyticus by PCR. Notably, the detection was shown to be functional at high annealing temperature above 68 degrees C. The groEL primers detected 100 pg and 1 ng of DNA purified from V. parahaemolyticus culture and artificially infected oyster tissue, respectively. CONCLUSIONS: The groEL gene is a potential marker for the species-specific detection of V. parahaemolyticus and could be used to detect this bacterium in contaminated food by PCR. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR using primers designed from groEL gene provide an efficient method for the accurate identification of V. parahaemolyticus from contaminated samples. PMID- 22053714 TI - Correct interpretation of T-ALL oncogene expression relies on normal human thymocyte subsets as reference material. PMID- 22053718 TI - Instructions to Contributors. PMID- 22053715 TI - Resolutions. PMID- 22053719 TI - Operative Dentistry Home Page. PMID- 22053720 TI - Comparison of intestinal parasitic infection in newly arrived and resident workers in Qatar. AB - BACKGROUND: The rapid growth of Qatar in the last two decades has been associated with an enormous expansion of building programs in its cities and in the provision of new service industries. This in turn has attracted a large influx of immigrant workers seeking employment in jobs associated with food handling, domestic service and the building industry. Many of these immigrants come from countries in the tropics and subtropics where intestinal parasitic infections are common. METHODS: We analyzed intestinal parasitic infections recorded in 2008 among immigrant and long-term resident workers in Doha city, Qatar (n = 1538). Stool examinations were carried out at the Hamad Medical Corporation and at the Medical Commission in Doha using standard procedures. RESULTS: Overall, 21.5% of subjects were infected with at least one of the species recorded (8 helminth and 4 protozoan species; the highest prevalence was for hookworms = 8.3%) and there were strong regional effects on prevalence of helminths, with subjects from North East Africa and Nepal showing particularly high prevalence. Most helminths declined in prevalence in subjects that acquired residency status in Qatar, especially among female subjects, but there was a marked exception among male Nepalese workers, who continued to harbour helminth infections (notably hookworms) after they became residents. Contrary to all other regional groups the prevalence of Giardia duodenalis was higher among Nepalese residents compared with new arrivals, while Blastocystis hominis infections were more common among residents of all regions, and especially among North East Africans. CONCLUSIONS: Our analysis has identified male Nepalese workers as a particular risk group continuing to harbour hookworm infection and G. duodenalis as residents, and subjects from North East Africa are as particularly likely to acquire B. hominis infection after settling in the country. These conclusions have important implications for the health authorities in Qatar. PMID- 22053721 TI - Collection of peptides released from single neurons with particle-embedded monolithic capillaries followed by detection with matrix-assisted laser desorption/ionization mass spectrometry. AB - Characterization of the stimulated release of neuropeptides from brain slices and individual cultured neurons requires efficient collection of the releasate from relatively large volumes of physiological saline. Here, several collection approaches are optimized using particle-embedded monolithic capillaries (PEMCs) with poly(stearyl methacrylate-co-ethylene glycol dimethacrylate) monolith acting as a "glue". Two distinct extraction particles, with either pyrrolidone (PY) or ethylenediamine (EDA) as the functional group on polystyrene backbone, have been embedded into capillaries having an inner diameter of 250 MUm. The capillaries act as collection devices for sampling neuropeptide release; the collection protocols are described, and the extraction efficiency of the probes are characterized. Specifically, the binding of angiotensin II from a peptide mixture onto the PY and EDA columns was 16 and 28 pmol, respectively, in a volume of 20 MUL of saline. The peptides released from these columns have been characterized via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry with low femtomole detection limits. When the PEMC columns were positioned in close proximity to individual neurons and 50 mM KCl was used as the secretagogue, peptides released from individual identified cultured neurons isolated from Aplysia californica were collected and characterized. PMID- 22053722 TI - Leishmania (Viannia) braziliensis: insights on subcellular distribution and biochemical properties of heparin-binding proteins. AB - Leishmaniasis is a vector-borne disease and an important public health issue. Glycosaminoglycan ligands in Leishmania parasites are potential targets for new strategies to control this disease. We report the subcellular distribution of heparin-binding proteins (HBPs) in Leishmania (Viannia) braziliensis and specific biochemical characteristics of L. (V.) braziliensis HBPs. Promastigotes were fractionated, and flagella and membrane samples were applied to HiTrap Heparin affinity chromatography columns. Heparin-bound fractions from flagella and membrane samples were designated HBP Ff and HBP Mf, respectively. Fraction HBP Ff presented a higher concentration of HBPs relative to HBP Mf, and SDS-PAGE analyses showed 2 major protein bands in both fractions (65 and 55 kDa). The 65 kDa band showed gelatinolytic activity and was sensitive to inhibition by 1,10 phenanthroline. The localization of HBPs on the promastigote surfaces was confirmed using surface plasmon resonance (SPR) biosensor analysis by binding the parasites to a heparin-coated sensor chip; that was inhibited in a dose-dependent manner by pre-incubating the parasites with variable concentrations of heparin, thus indicating distinct heparin-binding capacities for the two fractions. In conclusion, protein fractions isolated from either the flagella or membranes of L. (V.) braziliensis promastigotes have characteristics of metallo-proteinases and are able to bind to glycosaminoglycans. PMID- 22053723 TI - Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates. AB - The presence of alloreactive memory T cells is a major barrier for induction of tolerance in primates. In theory, delaying conditioning for tolerance induction until after organ transplantation could further decrease the efficacy of the regimen, since preexisting alloreactive memory T cells might be stimulated by the transplanted organ. Here, we show that such "delayed tolerance" can be induced in nonhuman primates through the mixed chimerism approach, if specific modifications to overcome/avoid donor-specific memory T-cell responses are provided. These modifications include adequate depletion of CD8+ memory T cells and timing of donor bone marrow administration to minimize levels of proinflammatory cytokines. Using this modified approach, mixed chimerism was induced successfully in 11 of 13 recipients of previously placed renal allografts and long-term survival without immunosuppression could be achieved in at least 6 of these 11 animals. PMID- 22053724 TI - Effect of staining and freezing media on sortability of stallion spermatozoa and their post-thaw viability after sex-sorting and cryopreservation. AB - Sex-sorted, frozen-thawed stallion spermatozoa remain out of reach of commercial horse breeders because of the low efficiency of the sex-sorting process and unacceptable fertility rates after insemination. Two experiments were designed to test the effects of alternative staining and freezing media to improve the viability of sex-sorted frozen-thawed stallion spermatozoa. Experiment 1 compared two freezing media, INRA 82((r)) and a modified lactose ethylenediaminetetraacetic acid (EDTA), for the cryopreservation of sex-sorted stallion spermatozoa. No significant differences between the two freezing media could be identified, suggesting that both cryodiluents would be suitable for incorporation into a sex-preselection protocol for stallion spermatozoa. Experiment 2 compared Kenney's modified Tyrode's (KMT) and Sperm TALP (Sp-TALP) as the staining and incubation medium for stallion spermatozoa prior to sex sorting. A significant increase in the percentage of acrosome-reacted spermatozoa occurred after staining and incubation in the clarified Sp-TALP compared with KMT. As no improvements in sorting rates were achieved using Sp-TALP, it was concluded that stallion sorting protocols could include KMT as the staining and incubation medium while either INRA 82((r)) or lactose-EDTA could be employed as a cryodiluents. PMID- 22053725 TI - The chemokine receptor CXCR4 and its ligand CXCL12 are activated during implantation and placentation in sheep. AB - BACKGROUND: The progression of implantation and placentation in ruminants is complex and is regulated by interplay between sex steroids and local signaling molecules, many of which have immune function. Chemokines and their receptors are pivotal factors in implantation and vascularization of the placenta. Based on known critical roles for chemokine receptor 4 (CXCR4) during early pregnancy in other species, we hypothesized that CXCR4 and its ligand CXCL12 would increase in the endometrium and conceptus in response to implantation in ewes. The objectives of the current study were to determine if CXCL12 and CXCR4 were upregulated in: endometrium from pregnant compared to non-pregnant ewes and in, conceptuses, cotyledons, caruncles and intercaruncular tissue. METHODS: Tissues were collected from sheep on Days 12, 13, 14, and 15 of either the estrous cycle or pregnancy and from pregnant ewes on Days 35 and 50. Blood samples from jugular and uterine vein were also collected on all days. Conceptuses were collected from mature ewes on Days 13, 15, 16, 17, 21 and 30 of gestation. Real time PCR was used to determine relative mRNA concentrations for CXCL12 and CXCR4 and Western blot analysis was employed to confirm protein concentration. RESULTS: Differences described are P < 0.05. In the endometrium, CXCR4 mRNA and protein was greater on Day 15 of pregnancy compared to the estrous cycle. CXCL12 and CXCR4 mRNA in conceptuses was greater on Days 21 and 30 compared to earlier days. CXCL12 mRNA was greater in cotyledons on Day 35 compared to Day 50. On Day 35 of gestation, CXCR4 was greater compared to Day 50 in caruncle and intercaruncular tissue. White blood cells obtained from jugular and uterine vein collection had the greatest mRNA concentration of CXCL12 on Day 35 of pregnancy. CONCLUSIONS: A comprehensive analysis of CXCL12 and CXCR4 expression in fetal and maternal tissues during early pregnancy is reported with noteworthy differences occurring during implantation and placentation in sheep. We interpreted these data to mean that the CXCL12/CXCR4 pathway is activated during implantation and placentation in sheep and is likely playing a role in the communication between trophoblast cells and the maternal endometrium. PMID- 22053726 TI - Triazole-linked-thiophene conjugate of calix[4]arene: its selective recognition of Zn2+ and as biomimetic model in supporting the events of the metal detoxification and oxidative stress involving metallothionein. AB - Supramolecular calix[4]arene conjugate (L) has been developed as a sensitive and selective sensor for Zn(2+) in HEPES buffer among the 12 metal ion by using fluorescence, absorption and ESI MS and also by visual fluorescent color. The structural, electronic, and emission properties of the calix[4]arene conjugates L and its zinc complex, [ZnL], have been demonstrated using ab initio density functional theory (DFT) combined with time-dependent density functional theory (TDDFT) calculations. The TDDFT calculations reveal the switch on fluorescence behavior of L is mainly due to the utilization of the lone pair of electrons on imine moiety by the Zn(2+). The resultant fluorescent complex, [ZnL], has been used as a secondary sensing chemo-ensemble for the detection of -SH containing molecules by removing Zn(2+) from [ZnL] and forming {Cys/DTT.Zn} adducts as equivalent to those present in metallothioneins. The displacement followed by the release of the coordinated zinc from its Cys/DTT complex by heavy metal ion (viz. Cd(2+) and Hg(2+)), as in the metal detoxification process or by ROS (such as H(2)O(2)) as in the oxidative stress, has been well demonstrated using the conjugate L through the fluorescence intensity retrieval wherein the fluorescence intensity is the same as that observed with [ZnL], which in turn mimics the zinc sensing element (MTF) in biology. PMID- 22053727 TI - Epidemiological survey of orthopedic joint dislocations based on nationwide insurance data in Taiwan, 2000-2005. AB - BACKGROUND: The epidemiology of acute orthopedic dislocations is poorly understood. A nationwide database provides a valuable resource for examining this issue in the Taiwanese population. METHODS: A 6-year retrospective cohort study of 1,000,000 randomly-sampled beneficiaries from the year 2005 was used as the original population. Based on the hospitalized and ambulatory data, the concomitant ICD9-CM diagnosis codes and treatment codes were evaluated and classified into 8 and 3 major categories, respectively. The cases matching both inclusive criteria of dislocation-related diagnosis codes and treatment codes were defined as incident cases. RESULTS: During 2000-2005, the estimated annual incidence (per 100,000 population) of total orthopedic dislocations in Taiwan was 42.1 (95%CI: 38.1-46.1). The major cause of these orthopedic dislocations was traffic accidents (57.4%), followed by accident falls (27.5%). The annual incidence dislocation by location was shoulder, 15.3; elbow, 7.7; wrist, 3.5; finger, 4.6; hip, 5.2; knee, 1.4; ankle, 2.0; and foot, 2.4. Approximately 16% of shoulder dislocations occurred with other concomitant fractures, compared with 17%, 53%, 16%, 76% and 52%, respectively, of dislocated elbow, wrist, hip, knee, and ankle cases. Including both simple and complex dislocated cases, the mean medical cost was US$612 for treatment of a shoulder dislocation, $504 for the elbow, $1,232 for the wrist, $1,103 for the hip, $1,888 for the knee, and $1,248 for the ankle. CONCLUSIONS: In Taiwan, three-quarters of all orthopedic dislocations were of the upper limbs. The most common complex fracture dislocation was of the knee, followed by the wrist and the ankle. Those usually needed a treatment combined with open reduction of fractures and resulted in a higher direct medical expenditure. PMID- 22053728 TI - Prolonged apnea during electroconvulsive therapy in monozygotic twins: case reports. AB - In the present work, we report two cases of monozygotic twins who developed prolonged apnea during electroconvulsive therapy (ECT) as a complication of anesthesia. In both cases, prolonged action of succinylcholine caused by a butyrylcholinesterase (BCHE) deficiency was confirmed by means of the dibucaine number test. In both cases, genetic analysis using the polymerase chain reaction revealed haplotype combined A and K variant mutations of the BCHE gene, both in the heterozygous form. These data show the potential risk of BCHE deficiency as a complication of anesthesia during ECT, and in particular underline the possible genetic contribution within a complex pathogenetic model. PMID- 22053729 TI - Honeybee glands as possible infection reservoirs of Nosema ceranae and Nosema apis in naturally infected forager bees. AB - AIMS: To determine whether Nosema ceranae and Nosema apis are present in different gland tissues of honeybee, Apis mellifera L. and to monitor spore presence and quantity in these glands in naturally infected hives from July 2009 to July 2010 in Quebec, Canada. METHODS AND RESULTS: Nosema spp. were quantified using duplex quantitative real-time PCR in the thoracic salivary, hypopharyngeal, mandibular glands, and venom sac and glands of A. mellifera over a period of 8 months. Both Nosema species were present in all the glands as single or mixed species; however, N. apis was not present as single-species detections in the salivary glands (see Table 2). Nosema ceranae was more prevalent throughout the 8 months. Significant correlative relationships were established for N. ceranae and N. apis levels in the honeybee glands and those found within the intestines of forager honeybees. Overall, the seasonality of N. ceranae and N. apis in the different glands tightly followed the seasonal patterns in the honeybee guts. CONCLUSIONS: Nosema ceranae and N. apis are not tissue specific, and honeybee glands have potential to become a useful indicator of the extent of disease in the colony and may represent a potential infection reservoir. SIGNIFICANCE AND IMPACT OF THE STUDY: First report of spore load quantification of Nosema spp. in different honeybee glands. PMID- 22053730 TI - Effect of rosmarinic acid on experimental diabetic nephropathy. AB - Connective tissue growth factor (CTGF) plays a pathogenic role in diabetic nephropathy (DN). Rosmarinic acid (RA) is a naturally occurring phenolic acid. This study was conducted to investigate the efficacy of RA on DN and to elucidate the potential mechanism. High glucose (HG)-stimulated cultured human renal proximal tubular epithelial cells (HK-2) analysed CTGF expression by western blotting, and it was investigated whether extracellular signal-regulated kinase (ERK) signalling pathway was involved. Using streptozotocin (STZ)-induced rat animal models, diabetic rats were randomized to receive intragastric (i.g.) doses of RA. Renal tissue, blood and urine samples were collected to determine biochemical index and analyse protein expression. In vitro study, RA reduced CTGF excretion in HG-induced HK-2 cells through the ERK signalling pathway. In an in vivo study, I.g. of RA 7.5 or 15 mg/kg significantly ameliorated renal function and increased body-weight. Meanwhile, RA reduced renal CTGF expression by immunohistochemical staining and reduced serum levels of CTGF. Besides, there were no significant differences in glycaemia levels between the RA groups compared with the STZ-treated group. Furthermore, RA ameliorated renal pathology. These results suggest that RA exerts an early renal protective role to DN. Inhibition of CTGF may be a potential target in DN therapy, which highlights the possibility of using RA in the treatment of DN. PMID- 22053733 TI - Operative Dentistry Home Page. PMID- 22053732 TI - Ultrasound-assisted synthesis of mesoporous zirconia-hydroxyapatite nanocomposites and their dual surface affinity for Cr3+/Cr2O7(2-) ions. AB - Zirconia-hydroxyapatite nanocomposites were prepared by sol-gel deposition of zirconium oxide from a zirconium alkoxide in the presence of apatite colloidal suspension under ultrasonication. The material porosity evolves from mainly microporous zirconia to mesoporous hydroxyapatite, with decreasing surface area and increasing pore volume. XRD studies indicate that the apatite phase is well preserved within the composite materials. The homogeneous dispersion of apatite colloids within the zirconia network was supported by TEM observations and nitrogen sorption measurements. (31)P solid-state NMR studies suggest that partial dissolution of apatite may have occurred during the preparation, leading to the adsorption of phosphate species on zirconia particles. This is confirmed by XRD studies of nanocomposites after thermal treatment that demonstrate the preferred formation of tetragonal over monoclinic ZrO(2) in the presence of hydroxyapatite. In order to investigate the surface properties of these novel materials, the adsorption of Pb(2+), Cr(3+), and Cr(2)O(7)(2-) was evaluated. Metal cations were preferentially adsorbed on apatite-rich composites, whereas Cr(2)O(7)(2-) shows a good affinity for the zirconia-rich phases. Zirconia apatite materials showed the most promising performance in terms of recyclability. These nanocomposites that combine microporosity, mesoporosity and dual sorption properties for these species appear as interesting materials for metal ion remediation and may also find applications as biomaterials. PMID- 22053731 TI - Complete genome sequence of Corynebacterium variabile DSM 44702 isolated from the surface of smear-ripened cheeses and insights into cheese ripening and flavor generation. AB - BACKGROUND: Corynebacterium variabile is part of the complex microflora on the surface of smear-ripened cheeses and contributes to the development of flavor and textural properties during cheese ripening. Still little is known about the metabolic processes and microbial interactions during the production of smear ripened cheeses. Therefore, the gene repertoire contributing to the lifestyle of the cheese isolate C. variabile DSM 44702 was deduced from the complete genome sequence to get a better understanding of this industrial process. RESULTS: The chromosome of C. variabile DSM 44702 is composed of 3, 433, 007 bp and contains 3, 071 protein-coding regions. A comparative analysis of this gene repertoire with that of other corynebacteria detected 1, 534 predicted genes to be specific for the cheese isolate. These genes might contribute to distinct metabolic capabilities of C. variabile, as several of them are associated with metabolic functions in cheese habitats by playing roles in the utilization of alternative carbon and sulphur sources, in amino acid metabolism, and fatty acid degradation. Relevant C. variabile genes confer the capability to catabolize gluconate, lactate, propionate, taurine, and gamma-aminobutyric acid and to utilize external caseins. In addition, C. variabile is equipped with several siderophore biosynthesis gene clusters for iron acquisition and an exceptional repertoire of AraC-regulated iron uptake systems. Moreover, C. variabile can produce acetoin, butanediol, and methanethiol, which are important flavor compounds in smear ripened cheeses. CONCLUSIONS: The genome sequence of C. variabile provides detailed insights into the distinct metabolic features of this bacterium, implying a strong adaption to the iron-depleted cheese surface habitat. By combining in silico data obtained from the genome annotation with previous experimental knowledge, occasional observations on genes that are involved in the complex metabolic capacity of C. variabile were integrated into a global view on the lifestyle of this species. PMID- 22053735 TI - Chemical composition of the essential oil of aerial parts of Haussknechtia elymaitica Boiss. from Iran: a good natural source for trans-asaron. AB - The chemical composition of the essential oil of Haussknechtia elymaitica Boiss. was investigated by capillary GC and GC/MS for the first time. Twelve components were identified which accounting for 99.7% of the oil composition. The major compounds were trans-asarone (59.9%), trans-methyl isoeugenol (22.4%), alpha zingiberene (7.96%), beta-sesquiphellandrene (4.7%) and beta-bisabolene (4.3%). The first three compounds considered as the main components of the essential oil were isolated and characterised by spectroscopic techniques. PMID- 22053736 TI - Reducing medical errors and adverse events. AB - Medical errors account for ~98,000 deaths per year in the United States. They increase disability and costs and decrease confidence in the health care system. We review several important types of medical errors and adverse events. We discuss medication errors, healthcare-acquired infections, falls, handoff errors, diagnostic errors, and surgical errors. We describe the impact of these errors, review causes and contributing factors, and provide an overview of strategies to reduce these events. We also discuss teamwork/safety culture, an important aspect in reducing medical errors. PMID- 22053737 TI - Wireless technology in disease management and medicine. AB - Healthcare information, and to some extent patient management, is progressing toward a wireless digital future. This change is driven partly by a desire to improve the current state of medicine using new technologies, partly by supply and-demand economics, and partly by the utility of wireless devices. Wired technology can be cumbersome for patient monitoring and can restrict the behavior of the monitored patients, introducing bias or artifacts. However, wireless technologies, while mitigating some of these issues, have introduced new problems such as data dropout and "information overload" for the clinical team. This review provides an overview of current wireless technology used for patient monitoring and disease management. We identify some of the major related issues and describe some existing and possible solutions. In particular, we discuss the rapidly evolving fields of telemedicine and mHealth in the context of increasingly resource-constrained healthcare systems. PMID- 22053738 TI - Geographic variation in health care. AB - Measurements of health care spending and outcomes in a geographic area and comparisons of one area to another have been used to make observations about health delivery systems and guide health care policy. Medicare claims files are a ready source of data about health care utilization and have served as the basis for a large number of studies in the United States. If ecologic studies are to accurately reflect local practices, potential variables must be accounted for. In the United States, differences in disease burden and socioeconomic factors are important variables affecting health care spending and outcomes. The assertion that regional variation in Medicare spending in the last two years of life is indicative of widespread waste in the U.S. health care system became a controversial part of the health care reform debate in 2009-2010. PMID- 22053740 TI - Circulating tumor cells and circulating tumor DNA. AB - Solid tumors derived from epithelial tissues (carcinomas) are responsible for 90% of all new cancers in Europe, and the main four tumor entities are breast, prostate, lung, and colon cancer. Present tumor staging is mainly based on local tumor extension, metastatic lymph node involvement, and evidence of overt distant metastasis obtained by imaging technologies. However, these staging procedures are not sensitive enough to detect early tumor cell dissemination as a key event in tumor progression. Many teams have therefore focused on the development of sensitive assays that allow the specific detection of single tumor cells or small amounts of cell-free tumor DNA in the peripheral blood of cancer patients. These methods allow the detection and characterization of early metastatic spread and will provide unique insights into the biology of metastatic progression of human tumors, including the effects of therapeutic interventions. PMID- 22053739 TI - Screening for prostate cancer: early detection or overdetection? AB - A sophisticated reading of the randomized trial evidence suggests that, although screening for prostate cancer with prostate-specific antigen (PSA) can reduce cancer-specific mortality, it does so at considerable cost in terms of the number of men who need to be screened, biopsied, and treated to prevent one death. The challenge is to design screening programs that maximize benefits (reducing prostate cancer mortality) and minimize costs (overtreatment). Recent research has suggested that this can be achieved by risk-stratifying screening and biopsy; increasing reliance on active surveillance for low-risk cancer; restricting radical prostatectomy to high-volume surgeons; and using appropriately high-dose radiotherapy. In current U.S. practice, however, many men who are screened are unlikely to benefit, most men found to have low-risk cancers are referred for unnecessary curative treatment, and much treatment is given at low-volume centers. PMID- 22053741 TI - Curcumin alleviates eosinophilic meningitis through reduction of eosinophil count following albendazole treatment against Angiostrongylus cantonensis in mice. AB - Angiostrongylus cantonensis (A. cantonensis) is the most common cause of parasitic eosinophilic meningitis worldwide. By using an animal model of BALB/c mice infected with A. cantonensis, previous studies indicated that the anthelmintic drug, albendazole, could kill A. cantonensis larvae and prevent further infection. However, the dead larvae will induce severe immune responses targeting at brain tissues. To alleviate the detrimental effects caused by the dead larvae, we administered curcumin, a traditional anti-inflammatory agent, as a complementary treatment in addition to albendazole therapy, to determine whether curcumin could be beneficial for treatment. The results showed that although curcumin treatment alone did not reduce worm number, combined treatment by albendazole and curcumin helped to reduce eosinophil count in the cerebrospinal fluid, better than using albendazole alone. This alleviating effect did not affect albendazole treatment alone, since histological analysis showed similar worm eradication with or without addition of curcumin. Nevertheless, curcumin treatment alone and combined albendazole-curcumin treatment did not inhibit MMP-9 expression in the brain tissue. In conclusion, curcumin, when used as a complementary treatment to albendazole, could help to alleviate eosinophilic meningitis through suppression of eosinophil count in the cerebrospinal fluid. PMID- 22053742 TI - Ultrasonic extraction of phenols from olive mill wastewater: comparison with conventional methods. AB - Recovery of phenols from olive mill wastewater (OMWW) was studied, comparing five sample preparation methods: filtration, solid-phase (SPE), liquid-liquid (LLE) and ultrasonic (US)-assisted extraction of liquid and solid (freeze-dried) OMWW. Results showed that ultrasonication is a good alternative to conventional solvent extractions, providing higher recoveries at both levels of individual and total phenol yields. Sonication of liquid OMWW in organic solvent was more efficient vs its nonassisted counterpart (agitation), but did not provide a representative phenol chromatogram due to ethyl acetate use. By contrast, the US-assisted extraction of freeze-dried OMWW (3 * 20 min) in 100% methanol (1.5 g/25 mL, w/v) offered the highest qualitative-quantitative phenol yields without any US-induced alterations. Moreover, freeze-drying is an excellent preservation of initial liquid OMWW, holding a great potential for delayed analysis. This study is also the first report that Slovenian OMWW may be utilized as a valuable source of phenols, especially hydroxytyrosol and tyrosol. PMID- 22053743 TI - Selective monobenzoylation of 1,2- and 1,3-diols catalyzed by Me2SnCl2 in water (organic solvent free) under mild conditions. AB - We have developed an efficient method for selective monobenzoylation of 1,2- and 1,3-diols in water catalyzed by Me(2)SnCl(2). Treatment of 1,2- and 1,3-diols with benzoyl chlorides, DMT-MM, and potassium carbonate in the presence of a catalytic amount of Me(2)SnCl(2) and DMAP in water at room temperature gave monobenzoates in up to 97% yield. PMID- 22053744 TI - Multiplexed sensing of ions with barcoded polyelectrolyte capsules. AB - Multiplexed detection of analytes is a challenge for numerous medical and biochemical applications. Many fluorescent particulate devices are being developed as ratiometric optical sensors to measure the concentration of intracellular analytes. The response of these sensors is based on changes of the emission intensity of analyte-sensitive probes, entrapped into the carrier system, which depends on the concentration of a specific analyte. However, there are a series of technical limits that prevent their use for quantitative detection of several analytes in parallel (e.g., emission crosstalk between different sensor molecules). Here we demonstrate that double-wall barcoded sensor capsules can be used for multiplexed analysis of proton, sodium, and potassium ions. The sensor detection methodology is based on porous microcapsules which carry ion-sensitive probes in their inner cavity for ion detection and a unique QD barcode in their outermost wall as tag for identification of individual sensors. The engineering of QD barcodes to capsules walls represents a promising strategy for optical multianalyte determination. PMID- 22053745 TI - Development of a dual-isotope procedure for the tagging and identification of manufactured products: application to explosives. AB - A novel chemical tagging approach, based on a dual-isotope procedure, is presented. The method has been applied to explosives tagging. The method is based on the addition to the explosive of two enriched isotopes of the same element, which may be already present within it, at a given molar ratio. This dual-isotope approach will give a unique fingerprint to the tagged explosive. Further, the authentication of the tagged explosive or its residues will be obtained by comparison of the ratio of molar fractions experimentally measured by inductively coupled plasma mass spectrometry (ICP-MS) with the molar fraction ratio of the tagging mixture. The novelty of this tagging method relies on working with isotope abundances and molar fraction ratios instead of the classical isotope ratios, and this fact constitutes the strong point of the described approach since the molar ratio is not affected by physical, chemical, or biochemical processes, and it is also not disturbed by environmental contamination with the natural abundance element. Furthermore, the use of molar fraction ratios overcomes the nonhomogeneous distribution of the tagging element within the explosive. As the tagging element can be present at trace or ultratrace levels, a very small amount of enriched isotopes needs to be added, denoting a low cost solution. Also, the use of enriched stable isotopes of nontoxic elements will have negligible health effects or affect the environment. PMID- 22053746 TI - Mechanistic insights into the dissociation and decomposition of carbonic acid in water via the hydroxide route: an ab initio metadynamics study. AB - The dissociation and decomposition of carbonic acid (H2CO3) in water are important reactions in the pH regulation in blood, CO2 transport in biological systems, and the global carbon cycle. H2CO3 is known to have three conformers [cis-cis (CC), cis-trans (CT), and trans-trans (TT)], but their individual reaction dynamics in water has not been probed experimentally. In this paper, we have investigated the energetics and mechanisms of the conformational changes, dissociation (H2CO3 -->/<-- HCO3(-) + H(+)), and decomposition via the hydroxide route (HCO3(-) --> CO2+OH(-)) of all three conformers of H2CO3 in water using Car Parrinello molecular dynamics (CPMD) in conjunction with metadynamics. It was found that, unlike in the gas phase, the interconversion between the various conformers occurs via two different pathways, one involving a change in one of the two dihedral angles (O=C-O-H) and the other a proton transfer through a hydrogen-bond wire. The free energy barriers/changes for the various conformational changes via the first pathway were calculated and contrasted with the previously calculated values for the gas phase. The CT and TT conformers were found to undergo decomposition in water via a two-step process: first, the dissociation and then the decomposition of HCO3(-) into CO2 and OH(-). The CC conformer does not directly decompose but first undergoes a conformational change to CT or TT prior to decomposition. This is in contrast with the concerted mechanism proposed for the gas phase, which involves a dehydroxylation of one of the OH groups and a simultaneous deprotonation of the other OH group to yield CO2 and H2O. The dissociation in water was seen to involve the repeated formation and breakage of a hydrogen-bond wire with neighboring water molecules, whereas the decomposition is initiated by the diffusion of H(+) away from HCO3(-); this decomposition mechanism differs from that proposed for the water route dehydration (HCO3(-) + H3O(+) --> CO2 + H2O), which involves the participation of a nearbyH3O(+) ion.Our calculated pKa values and decomposition free energy barriers for the CT and TT conformers are consistent with the overall experimental values of 3.45 and 22.28 kcal/mol, respectively, suggesting that the dynamics of the various conformers should be taken into account for a better understanding of aqueous H2CO3 chemistry. PMID- 22053747 TI - Shared familial aggregation of susceptibility to different manifestations of venous thromboembolism: a nationwide family study in Sweden. PMID- 22053748 TI - The influence of mapped hazards on risk beliefs: a proximity-based modeling approach. AB - Interview findings suggest perceived proximity to mapped hazards influences risk beliefs when people view environmental hazard maps. For dot maps, four attributes of mapped hazards influenced beliefs: hazard value, proximity, prevalence, and dot patterns. In order to quantify the collective influence of these attributes for viewers' perceived or actual map locations, we present a model to estimate proximity-based hazard or risk (PBH) and share study results that indicate how modeled PBH and map attributes influenced risk beliefs. The randomized survey study among 447 university students assessed risk beliefs for 24 dot maps that systematically varied by the four attributes. Maps depicted water test results for a fictitious hazardous substance in private residential wells and included a designated "you live here" location. Of the nine variables that assessed risk beliefs, the numerical susceptibility variable was most consistently and strongly related to map attributes and PBH. Hazard value, location in or out of a clustered dot pattern, and distance had the largest effects on susceptibility. Sometimes, hazard value interacted with other attributes, for example, distance had stronger effects on susceptibility for larger than smaller hazard values. For all combined maps, PBH explained about the same amount of variance in susceptibility as did attributes. Modeled PBH may have utility for studying the influence of proximity to mapped hazards on risk beliefs, protective behavior, and other dependent variables. Further work is needed to examine these influences for more realistic maps and representative study samples. PMID- 22053749 TI - 2,4-Pentanediolate as an alkoxide/diketonate "hybrid" ligand and the formation of aluminum and zirconium derivatives. AB - When 2,4-pentanediol (2,4-H(2)pd) is deprotonated, the resulting dianion (2,4-pd) serves as a type of "hybrid" ligand, i.e., an alkoxide that possesses structural features of a beta-diketonate. 2,4-Pentanediol reacts with Al(O-s-Bu)(3) and Zr(O i-Pr)(4) to form chelated multinuclear complexes. The aluminum-containing product is first isolated as the insoluble [Al(2,4-pd)(2,4-Hpd)](n); on sublimation, a hydrocarbon-soluble mixture of polymetallic species is generated. Mass spectral evidence suggests that both Al(4)(2,4-pd)(6) and Al(5)(2,4-pd)(7)(2,4-Hpd) are present. The zirconium complex is isolated as an adduct, [Zr(2,4-pd)(2)](2).(2,4 H(2)pd). The pentanediolates decompose on heating to form Al(2)O(3) and ZrO(2). Unlike the mononuclear Al(acac)(3) and Zr(acac)(4) derivatives (acac = acetylacetonate), the formation of aggregates with the 2,4-pd ligand suggests that the latter has more coordinative flexibility. The geometries of several model aluminum complexes with oxygen donor ligands were studied with density functional theory methods. The optimized structures were used with the gauge, including atomic orbital (GIAO) method to calculate their (27)Al NMR magnetic shielding values for comparison with experiment. PMID- 22053750 TI - Novel route to size-controlled Fe-MIL-88B-NH2 metal-organic framework nanocrystals. AB - A new approach for the synthesis of uniform metal-organic framework (MOF) nanocrystals with controlled sizes and aspect ratios has been developed using simultaneously the non-ionic triblock co-polymer F127 and acetic acid as stabilizing and deprotonating agents, respectively. The alkylene oxide segments of the triblock co-polymer can coordinate with metal ions and stabilize MOF nuclei in the early stage of the formation of MOF nanocrystals. Acetic acid can control the deprotonation of carboxylic linkers during the synthesis and, thus, enables the control of the rate of nucleation, leading to the tailoring of the size and aspect ratio (length/width) of nanocrystals. Fe-MIL-88B-NH(2), as an iron-based MOF crystal, was selected as a typical example to illustrate our approach. The results reveal that this approach is used for not only the synthesis of uniform nanocrystals but also the control of the size and aspect ratio of the materials. The size and aspect ratio of nanocrystals increase with an increase in the concentration of acetic acid in the synthetic mixture. The non ionic triblock co-polymer F127 and acetic acid can be easily removed from the Fe MIL-88B-NH(2) nanocrystal products by washing with ethanol, and thus, their amine groups are available for practical applications. The approach is expected to synthesize various nanosized carboxylate-based MOF members, such as MIL-53, MIL 89, MIL-100, and MIL-101. PMID- 22053751 TI - Anakinra potentiates the protective effects of etanercept in transplantation of marginal mass human islets in immunodeficient mice. AB - Anti-inflammatory agents are used routinely in clinical islet transplantation in an attempt to promote islet engraftment. Infliximab, and more recently etanercept, is being used to neutralize tumor necrosis factor alpha, but this tenet is based on limited preclinical data. One group has promoted the potential of combined etanercept with an IL-1 receptor antagonist, anakinra in a small clinical study, but without strong preclinical data to justify this approach. We therefore sought to evaluate the impact of combined anakinra and etanercept in a marginal islet mass transplant model using human islets in immunodeficient mice. The combination of anakinra and etanercept led to remarkable improvement in islet engraftment (control 36.4%; anakinra 53.9%; etanercept 45.45%; anakinra and etanercept 87.5% euglycemia, p < 0.05 by log-rank) compared to single-drug treated mice or controls. This translated into enhanced metabolic function (area under curve glucose tolerance), improved graft insulin content and marked reduction in beta-cell specific apoptotis (0.67% anakinra + etanercept vs. 23.5% control, p < 0.001). These results therefore strongly justify the combined short term use of anakinra and etanercept in human islet transplantation. PMID- 22053752 TI - Influences of metabolic traits on subclinical endometritis at different intervals postpartum in high milking cows. AB - Seventy pluriparous high-yielding cows were used to investigate the impact of metabolic traits and body condition score (BCS) during early lactation on subclinical endometritis diagnosed at weeks 5, 6 and 7 postpartum (pp). Blood samples were collected from animals with no peripartum problems from the second (W2) to seventh (W7) weeks pp to estimate some blood metabolites including non esterified fatty acids (NEFA), beta-hydroxybutyric acid (BHBA), blood glucose, total cholesterol (T-chol) and blood urea nitrogen (BUN). Reproductive tract examination was carried out at weeks 5, 6 and 7 pp by endometrial cytology (percentage of polymorphonuclear cells; PMN%). Based on PMN%, animals having <5% were defined as subclinical endometritis group (ENDM group) while animals unaffected by endometritis were defined as no subclinical endometritis group (NOENDM group). Animals with endometritis during week 5 were identified as ENDM5, during week 6 identified as ENDM6 and during week 7 identified as ENDM7 or animals with no endometritis during weeks 5 (NOENDM5), 6 (NOENDM6) and 7 (NOENDM7) pp. Animals diagnosed at week 5; BUN and BCS were lower p < 0.05 in ENDM 5 than NOENDM5 group at W2, W4, W6 and W7. Cows diagnosed at week 6; T-chol was significantly higher (p = 0.05) in ENDM6 group (279.2 +/- 12.5 mg/dl) than NOENDM6 group (246 +/- 9.5 mg/dl) at W7. Moreover, blood glucose was significantly low (p < 0.05) in ENDM6 group when compared to NOENDM group at W4 pp (49.2 +/- 1.8 vs 53.8 +/- 1.3 mg/dl). BCS was significantly lower (p < 0.001) in animals suffered from endometritis during week 7 when compared to NOENDM7 cows at W3, W4, W5, W6 and W7. In conclusion, lower blood glucose, BUN and BCS could be a risk factor for cytologically diagnosed endometritis at weeks 5, 6 and 7 pp. PMID- 22053753 TI - Colonoscopic high frequency mini-probe ultrasound is more accurate than conventional computed tomography in the local staging of colonic cancer. AB - AIM: Colonoscopic high frequency mini-probe ultrasound was compared prospectively with CT in the local staging of colonic cancer. METHOD: Consecutive patients undergoing surgical resection for colonic cancer were recruited. Preoperative 64 slice CT staging with multiplanar reconstruction was compared with colonoscopic high frequency mini-probe ultrasound using 12 MHz and 20 MHz probes. The three methods of staging (CT, 12 MHz ultrasound and 20 MHz ultrasound) were compared with the histological stage of the resected specimen. This was done using weighted kappa coefficients where weights of 0.7-0.8 were given to penalize disagreements of one level in either direction and weights of zero were given to penalize disagreements of more than one level in any direction. RESULTS: In total, 38 patients with colonic cancer were included. They were located in the sigmoid (n = 20), descending (n = 5), ascending (n = 2) and transverse colon (n = 1) and in the caecum (n = 7) and splenic (n = 2) and hepatic (n = 1) flexure. Histopathological assessment revealed seven pT1, four pT2, 25 pT3 and two pT4 cancers. In relation to the pathology the weighted kappa coefficients were 0.36 (SE = 0.14), 0.81 (SE = 0.16) and 0.81 (SE = 0.17) for CT, ultrasound 12 MHz and ultrasound 20 MHz. Histopathologically 15 (39.5%) patients were lymph node positive. The sensitivity, specificity and kappa coefficient for detection of nodal disease for CT were 80%, 47.8% and 0.25 (SE = 0.14) compared with 80%, 82.5% and 0.62 for 12 MHz ultrasound (SD = 0.14) and 23%, 90.5% and 0.15 (SD = 0.13) for 20 MHz ultrasound. CONCLUSION: Colonoscopic ultrasound is significantly more accurate than CT for T staging of colonic cancers. With respect to nodal status, 12 MHz ultrasound offers superior accuracy to CT or 20 MHz ultrasound. PMID- 22053754 TI - Chewing gum modifies state anxiety and alertness under conditions of social stress. AB - OBJECTIVES: The finding that chewing gum can moderate state anxiety under conditions of acute stress has proved difficult to replicate. The present study examines the extent to which chewing gum can moderate state anxiety under conditions of acute social stress. METHOD: In a between-participants design, 36 participants completed a task comprising a mock job interview (a variation on the Trier Social Stress Task, which included a mental arithmetic component) while either chewing gum or without chewing gum. Self-rated measures of mood and anxiety were taken at baseline, after a 10-minute presentation preparation stage, after the 10-minute presentation, and following a 5-minute recovery stage. RESULTS: Post-presentation measures reflected increased state anxiety and decreased self-rated calmness and contentedness. Chewing gum attenuated the rise in state anxiety while increasing self-rated alertness. Chewing gum did not affect contentedness or calmness. CONCLUSIONS: The findings indicate that chewing gum can act to reduce anxiety under conditions of acute social stress: a finding consistent with Scholey et al. Furthermore, the data add to the growing body of literature demonstrating that chewing gum can increase alertness. PMID- 22053755 TI - Orally administered L-ornithine elevates brain L-ornithine levels and has an anxiolytic-like effect in mice. AB - Intracerebroventricular injection of L-ornithine has demonstrated sedative and hypnotic effects in neonatal chicks exposed to acute stressful conditions. However, whether orally administered L-ornithine can reduce acute mental stress remains to be defined. To clarify the nutritional importance of L-ornithine in controlling the stress response, in Experiment 1 we first investigated whether orally administered L-ornithine can be transported into the brain of mice. Mice were orally administered L-ornithine (3 mmol/water 10 ml/kg, per os). L-Ornithine levels were significantly elevated in the cerebral cortex and hippocampus at 30 and 60 minutes post-administration. In Experiment 2, the effect of orally administered L-ornithine (0, 0.1875, 0.75 and 3 mmol/water 10 ml/kg, per os) on anxiety-like behavior in mice exposed to the elevated plus-maze test was examined at 30 minutes post-administration. There was a significant increase in the percentage of time spent and entries in the open arms in the group receiving 0.75 mmol of L-ornithine compared to the control group. Furthermore, locomotion activity in a novel environment was not significantly changed between the control group and 0.75 mmol of L-ornithine group in Experiment 3. Therefore, it appears that orally administrated L-ornithine is bioavailable to the rodent brain and reduces anxiety-like behavior as demonstrated by the elevated plus-maze test. PMID- 22053756 TI - Neuroprotective effects of anthocyanins on apoptosis induced by mitochondrial oxidative stress. AB - OBJECTIVES: Mitochondrial oxidative stress (MOS) is a major factor in the underlying pathology of many neurodegenerative diseases. Here, we investigated the neuroprotective effects of a unique class of nutraceutical antioxidants, anthocyanins, against MOS-induced death of cultured cerebellar granule neurons (CGNs). Callistephin and kuromanin are anthocyanins derived from strawberries and black rice, respectively, whose neuroprotective properties have yet to be examined in detail. METHODS: Glutathione (GSH)-sensitive MOS and intrinsic apoptosis were induced in CGNs by incubation with the Bcl-2 inhibitor, HA14-1. The effects of anthocyanin co-incubation on CGN survival were assessed. RESULTS: The anthocyanins demonstrated significant protection from MOS-induced apoptosis which was equivalent to that provided by the green tea polyphenol, epigallocatechin 3-gallate; however, neither anthocyanin was as effective as GSH at rescuing CGNs. Inhibition of Bcl-2 caused a significant reduction of mitochondrial GSH which was prevented by the anthocyanins. Furthermore, the anthocyanins inhibited iron-induced lipid peroxidation in rat brain homogenates and prevented cardiolipin oxidation induced by MOS in CGNs. MOS-induced mitochondrial fragmentation and proteolytic cleavage of the optic atrophy 1 (OPA1) fusion GTPase were also attenuated by the anthocyanins. Finally, the anthocyanins significantly enhanced GSH peroxidase activity in a cell-free assay. DISCUSSION: These data show that anthocyanins suppress MOS-induced apoptosis by preserving mitochondrial GSH and inhibiting cardiolipin oxidation and mitochondrial fragmentation. These nutraceutical antioxidants warrant further study as potential therapeutic agents for neurodegenerative diseases caused by MOS. PMID- 22053757 TI - Effect of chronic protein ingestion on tyrosine and tryptophan levels and catecholamine and serotonin synthesis in rat brain. AB - OBJECTIVES: Previous studies have shown that brain tyrosine (TYR) levels and catecholamine synthesis rate increase in rats as chronic dietary protein content increases from 2 to 10% (% weight). A single protein, casein, was examined. The present study explores how TYR levels and catecholamine synthesis (and tryptophan (TRP) levels and serotonin synthesis) change when different proteins are ingested chronically over the same range of dietary protein contents. METHODS: Male rats ingested for 8 days diets contain 2 or 10% protein (zein, gluten, casein, soy protein, or alpha-lactalbumin). On the last day, they were killed 2.5 hours into the dark period, 30 minutes after receiving an injection of m hydroxybenzylhydrazine, an inhibitor of aromatic l-amino acid decarboxylase. Brain samples were analyzed for amino acids, including 5-hydroxytryptophan (index of serotonin synthesis rate) and dihydroxyphenylalanine (index of catecholamine synthesis rate), by HPLC-electrochemical detection. RESULTS: TYR levels and catecholamine synthesis rate in brain were unaffected by the particular protein ingested. However, TRP levels and serotonin synthesis rate varied markedly, depending on the protein ingested, with effects being most prominent in the 10% protein groups. The effect of dietary protein on brain TRP correlated very highly with its effect on serotonin synthesis. DISCUSSION: The results indicate that the protein ingested can chronically modify TRP levels and serotonin synthesis in brain, but not TYR levels or catecholamine synthesis, with effects most distinct at an adequate level of protein intake (10%). PMID- 22053758 TI - Epidemiological link between low cholesterol and suicidality: a puzzle never finished. AB - A substantial body of evidence shows an association between an increased risk of suicide and naturally low or therapeutically lowered serum cholesterol. The nature of the association, however, remains unclear. The interrelationships of cholesterol, cholesterol-lowering medications, depressive disorders, and the risk of suicide are more likely to be multi-directional. On the one hand, low cholesterol may have direct effects on mood and suicidal behaviors. On the other hand, psychological conditions and the medications for treatment may influence eating and exercise habits, and subsequently cholesterol levels. There is also likelihood that cholesterol might be a bystander of the association between suicide and other factors. Overall, the association not only represents a public health concern, is indeed a scientific challenge. The aim of this contribution is to comprehensively update and critically review the epidemiological evidences. Efforts have been made to explain the discrepant results from previous studies. This paper is concluded with discussions of the direction and methodological challenges for future investigations. PMID- 22053760 TI - The next evolutionary synthesis: from Lamarck and Darwin to genomic variation and systems biology. AB - The evolutionary synthesis, the standard 20th century view of how evolutionary change occurs, is based on selection, heritable phenotypic variation and a very simple view of genes. It is therefore unable to incorporate two key aspects of modern molecular knowledge: first is the richness of genomic variation, so much more complicated than simple mutation, and second is the opaque relationship between the genotype and its resulting phenotype. Two new and important books shed some light on how we should view evolutionary change now. "Evolution: a view from the 21st century" by J.A. Shapiro (2011, FT Press Science, New Jersey, USA. pp. 246) examines the richness of genomic variation and its implications. "Transformations of Lamarckism: from Subtle Fluids to Molecular Biology" edited by S.B. Gissis & E. Jablonka (2011, MIT Press, Cambridge, USA. pp. 457) includes some 40 papers that anyone with an interest in the history of evolutionary thought and the relationship between the environment and the genome will want to read. This review discusses both books within the context of contemporary evolutionary thinking and points out that neither really comes to terms with today's key systems-biology question: how does mutation-induced variation in a molecular network generate variation in the resulting phenotype? PMID- 22053759 TI - Novel agents for anti-platelet therapy. AB - Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban) have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12) receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor) are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed. PMID- 22053761 TI - New biotechnological perspectives of a NADH oxidase variant from Thermus thermophilus HB27 as NAD+-recycling enzyme. AB - BACKGROUND: The number of biotransformations that use nicotinamide recycling systems is exponentially growing. For this reason one of the current challenges in biocatalysis is to develop and optimize more simple and efficient cofactor recycling systems. One promising approach to regenerate NAD+ pools is the use of NADH-oxidases that reduce oxygen to hydrogen peroxide while oxidizing NADH to NAD+. This class of enzymes may be applied to asymmetric reduction of prochiral substrates in order to obtain enantiopure compounds. RESULTS: The NADH-oxidase (NOX) presented here is a flavoenzyme which needs exogenous FAD or FMN to reach its maximum velocity. Interestingly, this enzyme is 6-fold hyperactivated by incubation at high temperatures (80 degrees C) under limiting concentrations of flavin cofactor, a change that remains stable even at low temperatures (37 degrees C). The hyperactivated form presented a high specific activity (37.5 U/mg) at low temperatures despite isolation from a thermophile source. Immobilization of NOX onto agarose activated with glyoxyl groups yielded the most stable enzyme preparation (6-fold more stable than the hyperactivated soluble enzyme). The immobilized derivative was able to be reactivated under physiological conditions after inactivation by high solvent concentrations. The inactivation/reactivation cycle could be repeated at least three times, recovering full NOX activity in all cases after the reactivation step. This immobilized catalyst is presented as a recycling partner for a thermophile alcohol dehydrogenase in order to perform the kinetic resolution secondary alcohols. CONCLUSION: We have designed, developed and characterized a heterogeneous and robust biocatalyst which has been used as recycling partner in the kinetic resolution of rac-1-phenylethanol. The high stability along with its capability to be reactivated makes this biocatalyst highly re-useable for cofactor recycling in redox biotransformations. PMID- 22053763 TI - Addressing health disparities through patient education: the development of culturally-tailored health education materials at Puentes de Salud. AB - The availability of culturally appropriate written health information is essential for promoting health in diverse populations. Lack of English fluency has been shown to negatively impact health outcomes for Latinos in the United States. The authors conducted a needs assessment at a clinic serving Latino immigrants, focusing on patients' health and previous experiences with written health information. Based on these results and a literature review, we developed 10 Spanish language brochures to better serve the target population. This article outlines the process of developing and implementing this intervention, which can serve as a model for similar projects targeting diverse populations. PMID- 22053762 TI - Electrocardiographic abnormalities associated with the metabolic syndrome and its components: the multi-ethnic study of atherosclerosis. AB - BACKGROUND: The association between metabolic syndrome and electrocardiographic (ECG) abnormalities is not well established. METHODS: ECG tracings of 6,765 men and women aged 45-84 years, free of clinical cardiovascular disease, from the Multi-Ethnic Study of Atherosclerosis were obtained (2000-2002) and classified as normal or having major or minor abnormalities. We evaluated the associations of metabolic syndrome and its components with ECG abnormalities, adjusting for age, ethnicity, and gender and testing for effect modification by ethnicity and gender. RESULTS: The associations of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied significantly by gender. In males, metabolic syndrome and hypertension were significantly associated with major ECG abnormality [1.69 (1.33-2.13), and 2.22 (1.72-2.86), respectively] after adjusting for ethnicity and gender. Hypertension was also associated significantly with minor ECG abnormality in males after adjusting for age and ethnicity. In females, metabolic syndrome and hypertension were significantly associated with major [1.84 (1.44-2.37), and 1.68 (1.27-2.22), respectively] and minor [1.38 (1.19-1.59), and 1.53 (1.32-1.79), respectively] ECG abnormalities after adjusting for age and ethnicity. High triglycerides were only significantly associated with major ECG abnormality in females after adjusting for age and ethnicity. After adjusting for age, ethnicity, and gender, central obesity and high fasting blood glucose were significantly associated with major and minor ECG abnormalities, whereas low high-density lipoprotein cholesterol was significantly associated with major ECG abnormality only. CONCLUSIONS: Metabolic syndrome and its components are associated with major and/or minor ECG abnormalities. The relationship of metabolic syndrome, hypertension, and high triglycerides with ECG abnormalities varied according to gender. PMID- 22053765 TI - Factors influencing parental decision making when parents choose to deviate from the standard pediatric immunization schedule. AB - PURPOSE: The purpose of this article is to present the results of a study focusing on the basis for parental decisions to refrain from the standard pediatric immunization schedule. DESIGN AND METHODS: The study was based upon open-ended qualitative items that were subjected to content analysis to identify the prominent themes cited by parents. RESULTS: The results of the study demonstrate the presence of a variety of continuing misperceptions regarding the risks represented by common pediatric immunizations. PRACTICE IMPLICATIONS: The study demonstrates the need for intensive efforts designed to apprise families of the risks and benefits associated with pediatric immunization. PMID- 22053764 TI - Factors associated with the overuse or underuse of health care services among medical aid beneficiaries in Korea. AB - PURPOSE: To compare and contrast demographic characteristics and health care service utilization between overusers and underusers of health care services and to identify factors associated with the overuse or underuse of health care services among the medical aid beneficiaries in Korea. METHODS: Secondary data analysis was performed using health care costs and medical aid case management progress data. Data on demographic characteristics, health-related quality of life (HRQoL), and inappropriate health care service user category (overuse or underuse) were provided by the Medical-Aid Case Management Center of Korea, and heath care service reimbursement data were provided by the Korea National Health Insurance Corporation (NHIC). Data on 22,697 beneficiaries were used for analysis, and logistic regression analysis was conducted to examine factors that are associated with overuse and underuse of health care services. RESULTS: The study results revealed that older individuals, women, unemployed individuals, type 1 medical aid beneficiaries, and those with higher education and disabilities were more likely to belong to the overuse group, but urban residents, compared to metropolitan residents, and those with higher HRQoL were more likely to belong to the underuse group (p < .05). CONCLUSIONS: Understanding factors associated with the overuse or underuse of health care services may help to provide tailored case management services to improve the HRQoL of the beneficiaries and optimize their use of health care services. CLINICAL RELEVANCE: Promoting appropriate use of health care services may enhance clients' quality of life and preserve resources for other essential services for medical aid beneficiaries. PMID- 22053766 TI - Community program to prevent diabetes in school children. AB - There is an alarming increase in obesity and type- 2 diabetes in children. This article describes the process used to develop a diabetes prevention education program led by a group of volunteers from a community. Professionals in the field of nursing, education, nutrition, physical education, and fitness combined their expertise to develop content on diabetes and healthy life styles for third and fourth graders. The focus is an overview on diabetes education, nutrition, and physical activity using a highly interactive environment for the program. PMID- 22053767 TI - Stress and depression among Latina women in rural southeastern North Carolina. AB - The purposes of this study were to assess the level of depression and types of major stressors, and to identify stressors contributing to depression, among 135 Latina women in rural southeastern North Carolina. Nearly half of the participants (47.6%) had scores of greater than, or equal to, 16 on the Center for Epidemiologic Studies Depression Scale, used to identify possible depression, suggesting the need for early intervention. "Difficult to be away from family members," "immigration status," and "religion" were the most reliable predictors of stress, accounting for 34.5% of the total variance in depression. PMID- 22053770 TI - Beliefs about who should be tested for HIV among African American individuals attending a family practice clinic. PMID- 22053774 TI - Erratum. PMID- 22053771 TI - Identification of novel targets for breast cancer by exploring gene switches on a genome scale. AB - BACKGROUND: An important feature that emerges from analyzing gene regulatory networks is the "switch-like behavior" or "bistability", a dynamic feature of a particular gene to preferentially toggle between two steady-states. The state of gene switches plays pivotal roles in cell fate decision, but identifying switches has been difficult. Therefore a challenge confronting the field is to be able to systematically identify gene switches. RESULTS: We propose a top-down mining approach to exploring gene switches on a genome-scale level. Theoretical analysis, proof-of-concept examples, and experimental studies demonstrate the ability of our mining approach to identify bistable genes by sampling across a variety of different conditions. Applying the approach to human breast cancer data identified genes that show bimodality within the cancer samples, such as estrogen receptor (ER) and ERBB2, as well as genes that show bimodality between cancer and non-cancer samples, where tumor-associated calcium signal transducer 2 (TACSTD2) is uncovered. We further suggest a likely transcription factor that regulates TACSTD2. CONCLUSIONS: Our mining approach demonstrates that one can capitalize on genome-wide expression profiling to capture dynamic properties of a complex network. To the best of our knowledge, this is the first attempt in applying mining approaches to explore gene switches on a genome-scale, and the identification of TACSTD2 demonstrates that single cell-level bistability can be predicted from microarray data. Experimental confirmation of the computational results suggest TACSTD2 could be a potential biomarker and attractive candidate for drug therapy against both ER+ and ER- subtypes of breast cancer, including the triple negative subtype. PMID- 22053775 TI - The efficacy of a brief intervention in reducing hazardous drinking in working age men in Russia: the HIM (Health for Izhevsk men) individually randomised parallel group exploratory trial. AB - BACKGROUND: Russia has particularly low life expectancy for an industrialised country, with mortality at working ages having fluctuated dramatically over the past few decades, particularly among men. Alcohol has been identified as the most likely cause of these temporal variations. One approach to reducing the alcohol problem in Russia is 'brief interventions' which seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behaviour change. Very few studies to evaluate the efficacy of brief interventions in Russia have been conducted. Motivational Interviewing (MI) is a person-centred counselling style which can be adapted to brief interventions in which help is offered in thinking through behaviour in the context of values and goals, to decide whether change is needed, and if so, how it may best be achieved. METHODS: This paper reports on an individually randomised two-armed parallel group exploratory trial. The primary hypothesis is that a brief adaptation of MI will be effective in reducing self-reported hazardous and harmful drinking at 3 months. Participants were drawn from the Izhevsk Family Study II, with eligibility determined based on proxy reports of hazardous and harmful drinking in the past year. All participants underwent a health check, with MI subsequently delivered to those in the intervention arm. Signed consent was obtained from those in the intervention arm only at this point. Both groups were then invited for 3 and 12 month follow ups. The control group did not receive any additional intervention. RESULTS: 441 men were randomised. Of these 61 did not have a health check leaving 190 in each trial arm. Follow up at 3 months was high (97% of those having a health check), and very similar in the two trial arms (183 in the intervention and 187 in the control). No significant differences were detected between the randomised groups in either the primary or the secondary outcomes at three months in the intention to treat analyses. The unadjusted odds ratio (95% CI) for the effect of MI on hazardous and harmful drinking was 0.77 (0.51, 1.16). An adjusted odds ratio of 0.52 (0.28, 0.94) was obtained in the pre-specified per protocol analysis. CONCLUSIONS: This trial demonstrates that it is possible to engage Russian men who drink hazardously in a brief intervention aimed at reducing alcohol related harm. However the results with respect to the efficacy are equivocal and further, larger-scale trials are warranted. TRIAL REGISTRATION: ISRCTN: ISRCTN82405938. PMID- 22053776 TI - Factors influencing benzene formation from the decarboxylation of benzoate in liquid model systems. AB - Benzene may occur in foods due to the oxidative decarboxylation of benzoate in the presence of hydroxyl radicals. This study investigated factors influencing benzene formation in liquid model systems. The type of buffer, other sources of hydroxyl radical formation in food (photo oxidation of riboflavin and lipid oxidation), transition metal ion concentrations, and the inhibitory effect of antioxidants were tested in benzoate containing model systems. Regarding the hydroxyl radical sources tested, the highest benzene formation was observed in light exposed model systems containing ascorbic acid, Cu(2+), and riboflavin in Na-citrate buffer (1250 +/- 131 MUg kg(-1)). In practice, it seems that the combination ascorbic acid/transition metal ion remains the biggest contributor to benzene formation in food. However, the concentration of Cu(2+) influences significantly benzene formation in such a system with highest benzene yields observed for Cu(2+) 50 MUM (1400 MUg kg(-1)). The presence of antioxidants with metal chelation or reduction properties could prevent completely benzene formation. PMID- 22053777 TI - Dicer-labile PEG conjugates for siRNA delivery. AB - Poly(ethylene glycol) (PEG) conjugates of Dicer-substrate small interfering RNA (DsiRNA) have been prepared to investigate a new siRNA release strategy. 3'-sense or 5'-antisense thiol-modified, blunt-ended DsiRNAs, inhibiting enhanced green fluorescent protein (eGFP) expression, were covalently conjugated to PEG with varying molecular weights (2, 10, and 20 kg/mol) through a stable thioether bond using a Michael addition reaction. The DsiRNA conjugates with 2 kg/mol PEG (both 3'-sense or 5'-antisense strand conjugated) and the 10 kg/mol PEG conjugated to the 3'-sense strand of DsiRNA were efficiently cleaved by recombinant human Dicer to 21-mer siRNA, as determined by gel electrophoresis. Importantly, 2 and 10 kg/mol PEG conjugated to the 3'-sense strand of DsiRNA showed potent gene silencing activity in human neuroblastoma (SH-EP) cells, stably expressing eGFP, at both the mRNA and protein levels. Moreover, the 10 kg/mol PEG conjugates of the 3'-sense strand of DsiRNA were less immunogenic when compared with the unmodified DsiRNA, determined via an immune stimulation assay on human peripheral blood mononuclear cells. PMID- 22053779 TI - Solvent-dependent reactions for the synthesis of beta-keto-benzo-delta-sultone scaffolds via DBU-catalyzed O-sulfonylation/intramolecular Baylis-Hillman/1,3-H shift or dehydration tandem sequences. AB - We have developed a solvent-dependent method for the synthesis of novel benzo delta-sultone scaffolds. A variety of benzylbenzo[e][1,2]oxathiin-4(3H)-one-2,2 dioxides were obtained in high yields in DMF using a one-pot, DBU-catalyzed condensation of 2-hydroxybenzaldehydes with a number of (E)-2 phenylethenesulfonyl chlorides. On the other hand, the initially prepared 2 formylphenyl-(E)-2-phenylethenesulfonate derivatives underwent DBU-catalyzed reactions to a series of 3-[methoxy(phenyl)methyl]benzo[e][1,2]oxathiine-2,2 dioxides in moderate to good yields in MeOH. These reactions presumably proceed via DBU-catalyzed O-sulfonylation/intramolecular Baylis-Hillman/1,3-H shift or dehydration tandem sequences, respectively. PMID- 22053780 TI - Event-tree analysis with imprecise probabilities. AB - Novel methods are proposed for dealing with event-tree analysis under imprecise probabilities, where one could measure chance or uncertainty without sharp numerical probabilities and express available evidence as upper and lower previsions (or expectations) of gambles (or bounded real functions). Sets of upper and lower previsions generate a convex set of probability distributions (or measures). Any probability distribution in this convex set should be considered in the event-tree analysis. This article focuses on the calculation of upper and lower bounds of the prevision (or the probability) of some outcome at the bottom of the event-tree. Three cases of given information/judgments on probabilities of outcomes are considered: (1) probabilities conditional to the occurrence of the event at the upper level; (2) total probabilities of occurrences, that is, not conditional to other events; (3) the combination of the previous two cases. Corresponding algorithms with imprecise probabilities under the three cases are explained and illustrated by simple examples. PMID- 22053781 TI - Saccharide-functionalized alkanethiols for fouling-resistant self-assembled monolayers: synthesis, monolayer properties, and antifouling behavior. AB - We describe the synthesis of a series of mono-, di-, and trisaccharide functionalized alkanethiols as well as the formation of fouling-resistant self assembled monolayers (SAMs) from these. The SAMs were characterized using ellipsometry, wetting measurements, and infrared reflection-absorption spectroscopy (IRAS). We show that the structure of the carbohydrate moiety affects the packing density and that this also alters the alkane chain organization. Upon increasing the size of the sugar moieties (from mono- to di- and trisaccharides), the structural qualities of the monolayers deteriorated with increasing disorder, and for the trisaccharide, slow reorganization dynamics in response to changes in the environmental polarity were observed. The antifouling properties of these SAMs were investigated through protein adsorption experiments from buffer solutions as well as settlement (attachment) tests using two common marine fouling species, zoospores of the green macroalga Ulva linza and cypris larvae of the barnacle Balanus amphitrite. The SAMs showed overall good resistance to fouling by both the proteins and the tested marine organisms. To improve the packing density of the SAMs with bulky headgroups, we employed mixed SAMs where the saccharide-thiols are diluted with a filler molecule having a small 2-hydroxyethyl headgroup. This method also provides a means by which the steric availability of sugar moieties can be varied, which is of interest for specific interaction studies with surface-bound sugars. The results of the surface dilution study and the low nonspecific adsorption onto the SAMs both indicate the feasibility of this approach. PMID- 22053782 TI - Single nuclei Raman spectroscopy for drug evaluation. AB - Detection of cellular changes at single-cell level has a great potential for biomedical and biopharmaceutical applications. Raman spectroscopy is an important tool for single-cell molecular imaging analysis. Raman spectroscopy can provide time-resolved information of the selected biomolecular distributions inside a single cell without the need of chemical labeling. In this study, we monitored the cellular responses to antineoplastic drug at a single cell basis with Raman spectroscopy. We demonstrated that single nuclei Raman spectroscopy has the ability to detect and identify nuclear changes related to cytotoxicity at lower concentrations and in shorter time span than conventional cell based assays. Thus, this strategy of using Raman spectroscopy of single, isolated nuclei may be very valuable for rapid and sensitive detection of cellular changes in response to chemotherapeutic agents. PMID- 22053783 TI - HCO3(-) formation from CO2 at high pH: ab initio molecular dynamics study. AB - Ab initio molecular dynamics simulations have been performed to study the dissolution of CO2 in water at high pH. The CO2 + OH(-) --> HCO3(-) forward and the HCO3(-) --> CO2 + OH(-) reverse paths have been simulated by employing the metadynamics technics. We have found that the free energy barrier along the forward direction is predominantly hydration related and significantly entropic in origin, whereas the backward barrier is primarily enthalpic. The main motifs in the forward mechanism are the structural diffusion of the hydroxyl ion to the first hydration sphere of CO2, its desolvation, and the C-O bond formation in concert with the CO2 bending within the hydrate cavity. In the reverse reaction, the origin of the barrier is the rupture of the strong C-O(H) bond. The present findings support the notion that the free energy barrier of the bicarbonate formation is strongly solvation related but provide also additional mechanistic details at the molecular level. PMID- 22053784 TI - Vacuolated lymphocytes and abnormal eosinophils in GM1 gangliosidosis, type 1. PMID- 22053785 TI - Digital transplantation pathology: combining whole slide imaging, multiplex staining and automated image analysis. AB - Conventional histopathology is the gold standard for allograft monitoring, but its value proposition is increasingly questioned. "-Omics" analysis of tissues, peripheral blood and fluids and targeted serologic studies provide mechanistic insights into allograft injury not currently provided by conventional histology. Microscopic biopsy analysis, however, provides valuable and unique information: (a) spatial-temporal relationships; (b) rare events/cells; (c) complex structural context; and (d) integration into a "systems" model. Nevertheless, except for immunostaining, no transformative advancements have "modernized" routine microscopy in over 100 years. Pathologists now team with hardware and software engineers to exploit remarkable developments in digital imaging, nanoparticle multiplex staining, and computational image analysis software to bridge the traditional histology-global "-omic" analyses gap. Included are side-by-side comparisons, objective biopsy finding quantification, multiplexing, automated image analysis, and electronic data and resource sharing. Current utilization for teaching, quality assurance, conferencing, consultations, research and clinical trials is evolving toward implementation for low-volume, high-complexity clinical services like transplantation pathology. Cost, complexities of implementation, fluid/evolving standards, and unsettled medical/legal and regulatory issues remain as challenges. Regardless, challenges will be overcome and these technologies will enable transplant pathologists to increase information extraction from tissue specimens and contribute to cross-platform biomarker discovery for improved outcomes. PMID- 22053786 TI - Two-dimensional coalescence dynamics of encapsulated metallofullerenes in carbon nanotubes. AB - We report on the coalescence of a two-dimensional (2D) chain of La@C(82) metallofullerene molecules encapsulated inside a single-wall carbon nanotube (SWNT). 2D packing of metallofullerenes is known to adopt a zigzag arrangement and cause elliptical distortion to the cross-section of the SWNT host. We show that after coalescence of the metallofullerenes into an inner nanotube the carbon nanotube host returns to its original circular cross-section. This is due to a relaxation of the strain caused by the packing of the encapsulated La@C(82) molecules into the nanotube. We identify the formation of some novel but transient fullerene-based structures formed during the intermediate stages of coalescence of the La@C(82) into an inner nanotube. These results highlight the flexible nature of SWNTs and their ability to adapt their cross-sectional profile depending upon forces induced by material encapsulated within. PMID- 22053787 TI - Long-term results of stapled haemorrhoidopexy in a prospective single centre study of 153 patients with 1-6 years' follow-up. AB - AIM: The long-term results of stapled haemorrhoidopexy for prolapsed haemorrhoids were assessed using uniform methods to acquire data and pre-set definitions of failure, recurrence, residual symptoms and impaired continence. METHOD: From October 1999 to May 2005, 153 patients underwent a stapled haemorrhoidopexy and were enrolled prospectively. They were assessed preoperatively, postoperatively and at the end of the study from replies to a questionnaire about symptoms and continence. Preoperatively, manual reduction of prolapse was required in 103 patients, skin tags were found in 115 patients (circumferential in 22) and impaired continence in 63. RESULTS: In all, 145 patients completed preoperative and long-term protocols and were analysed as paired data, at a mean follow-up of 32 months. Failure to control the prolapse or recurrence was seen in 19 (13%) patients including nine reoperations for prolapse. Symptoms improved from 8.1 to 2.5 points on a 15-point scale (P = 0.001). Symptoms were not controlled in 25 (17%) patients. Continence improved from 4.7 to 2.9 points on a 15-point scale (P = 0.001). Twenty-five (17%) patients still had a continence disturbance. Altogether 51 (35%) patients had a deficient outcome with respect to prolapse, symptoms or continence. There were no major adverse events. CONCLUSION: Restoration of the anal anatomy by stapled haemorrhoidopexy resulted in a significant improvement in haemorrhoid-associated symptoms and continence but a third of patients had poor symptom control including 13% with persisting prolapse. PMID- 22053788 TI - Artisanal salt production in Aveiro/Portugal - an ecofriendly process. AB - Solar salinas are man-made systems exploited for the extraction of salt, by solar and wind evaporation of seawater. Salt production achieved by traditional methods is associated with landscapes and environmental and patrimonial values generated throughout history. Since the mid-twentieth century, this activity has been facing a marked decline in Portugal, with most salinas either abandoned or subjected to destruction, making it necessary to find a strategy to reverse this trend.It is, however, possible to generate revenue from salinas at several levels, not merely in terms of good quality salt production, but also by obtaining other products that can be commercialized, or by exploring their potential for tourism, and as research facilities, among others. Furthermore, with an adequate management, biodiversity can be restored to abandoned salinas, which constitute important feeding and breeding grounds for resident and migratory aquatic birds, many of which are protected by European Community Directives.The aims of this manuscript are to present a brief overview on the current state of sea salt exploitation in Portugal and to stress the importance of recovering these salinas for the conservation of this particular environment, for the regional economy, the scientific community and the general public. The Aveiro salina complex is presented in detail, to exemplify salina structure and functioning, as well as current problems and potential solutions for artisanal salinas. PMID- 22053789 TI - Characterization of the PilN, PilO and PilP type IVa pilus subcomplex. AB - Type IVa pili are bacterial nanomachines required for colonization of surfaces, but little is known about the organization of proteins in this system. The Pseudomonas aeruginosa pilMNOPQ operon encodes five key members of the transenvelope complex facilitating pilus function. While PilQ forms the outer membrane secretin pore, the functions of the inner membrane-associated proteins PilM/N/O/P are less well defined. Structural characterization of a stable C terminal fragment of PilP (PilP(Delta71)) by NMR revealed a modified beta sandwich fold, similar to that of Neisseria meningitidis PilP, although complementation experiments showed that the two proteins are not interchangeable likely due to divergent surface properties. PilP is an inner membrane putative lipoprotein, but mutagenesis of the putative lipobox had no effect on the localization and function of PilP. A larger fragment, PilP(Delta18-6His), co purified with a PilN(Delta44)/PilO(Delta51) heterodimer as a stable complex that eluted from a size exclusion chromatography column as a single peak with a molecular weight equivalent to two heterotrimers with 1:1:1 stoichiometry. Although PilO forms both homodimers and PilN-PilO heterodimers, PilP(Delta18 6His) did not interact stably with PilO(Delta51) alone. Together these data demonstrate that PilN/PilO/PilP interact directly to form a stable heterotrimeric complex, explaining the dispensability of PilP's lipid anchor for localization and function. PMID- 22053790 TI - Is there any relationship between physical activity level and patterns, and physical performance in children? AB - BACKGROUND: It is often assumed that physical activity (PA) and physical performance during childhood and adolescence are beneficial for health during adulthood, but a positive relationship between PA and physical performance has not been precisely clarified in children. The lack or the weakness of the relationships between PA and physical performance could be due to the measure of PA. If the use of accelerometry is considered as an objective and common measure of PA, the real patterns of children's habitual PA must be reflected. The aim of this study was to investigate the relationship between the levels and patterns of PA assessed with high frequency accelerometry and physical performance in young children. METHODS: Eighty-six boys and 101 girls aged 6-12 years participated in this study. Physical activity was measured over a 7-day period, using a 5-s epoch. Physical performance was assessed by means of EUROFIT tests (anthropometrics, standing broad jump, the 10 * 5 meter shuttle run, the sit-and reach, the handgrip, the number of sit-ups in 30 seconds, the 20-meter shuttle run). RESULTS: No relationship was found between PA and physical performance. In boys only, body fatness was negatively associated with vigorous PA (r = -0.38, p < 0.001) and very high PA (r = -0.35, p < 0.01), in contrast to light PA (r = 0.28, p < 0.01), which was positively related to body fatness. CONCLUSION: In 6- to- 12 year- old children, the more active children were not the fittest. Our results also underline the need for uniformity in approach to measurement of PA, body composition and health-related fitness between studies. PMID- 22053797 TI - Chemistry of diglycolamides: promising extractants for actinide partitioning. PMID- 22053792 TI - Myc and Miz-1 have coordinate genomic functions including targeting Hox genes in human embryonic stem cells. AB - BACKGROUND: A proposed role for Myc in maintaining mouse embryonic stem (ES) cell pluripotency is transcriptional repression of key differentiation-promoting genes, but detail of the mechanism has remained an important open topic. RESULTS: To test the hypothesis that the zinc finger protein Miz-1 plays a central role, in the present work we conducted chromatin immunoprecipitation/microarray (ChIP chip) analysis of Myc and Miz-1 in human ES cells, finding homeobox (Hox) genes as the most significant functional class of Miz-1 direct targets. Miz-1 differentiation-associated target genes specifically lack acetylated lysine 9 and trimethylated lysine 4 of histone H3 (AcH3K9 and H3K4me3) 9 histone marks, consistent with a repressed transcriptional state. Almost 30% of Miz-1 targets are also bound by Myc and these cobound genes are mostly factors that promote differentiation including Hox genes. Knockdown of Myc increased expression of differentiation genes directly bound by Myc and Miz-1, while a subset of the same genes is downregulated by Miz-1 loss-of-function. Myc and Miz-1 proteins interact with each other and associate with several corepressor factors in ES cells, suggesting a mechanism of repression of differentiation genes. CONCLUSIONS: Taken together our data indicate that Miz-1 and Myc maintain human ES cell pluripotency by coordinately suppressing differentiation genes, particularly Hox genes. These data also support a new model of how Myc and Miz-1 function on chromatin. PMID- 22053798 TI - [Copyright in Ugeskrift for Laeger and Danish Medical Bullletin]. PMID- 22053791 TI - Genetic variability of transcript abundance in pig peri-mortem skeletal muscle: eQTL localized genes involved in stress response, cell death, muscle disorders and metabolism. AB - BACKGROUND: The genetics of transcript-level variation is an exciting field that has recently given rise to many studies. Genetical genomics studies have mainly focused on cell lines, blood cells or adipose tissues, from human clinical samples or mice inbred lines. Few eQTL studies have focused on animal tissues sampled from outbred populations to reflect natural genetic variation of gene expression levels in animals. In this work, we analyzed gene expression in a whole tissue, pig skeletal muscle sampled from individuals from a half sib F2 family shortly after slaughtering. RESULTS: QTL detection on transcriptome measurements was performed on a family structured population. The analysis identified 335 eQTLs affecting the expression of 272 transcripts. The ontologic annotation of these eQTLs revealed an over-representation of genes encoding proteins involved in processes that are expected to be induced during muscle development and metabolism, cell morphology, assembly and organization and also in stress response and apoptosis. A gene functional network approach was used to evidence existing biological relationships between all the genes whose expression levels are influenced by eQTLs. eQTLs localization revealed a significant clustered organization of about half the genes located on segments of chromosome 1, 2, 10, 13, 16, and 18. Finally, the combined expression and genetic approaches pointed to putative cis-drivers of gene expression programs in skeletal muscle as COQ4 (SSC1), LOC100513192 (SSC18) where both the gene transcription unit and the eQTL affecting its expression level were shown to be localized in the same genomic region. This suggests cis-causing genetic polymorphims affecting gene expression levels, with (e.g. COQ4) or without (e.g. LOC100513192) potential pleiotropic effects that affect the expression of other genes (cluster of trans eQTLs). CONCLUSION: Genetic analysis of transcription levels revealed dependence among molecular phenotypes as being affected by variation at the same loci. We observed the genetic variation of molecular phenotypes in a specific situation of cellular stress thus contributing to a better description of muscle physiologic response. In turn, this suggests that large amounts of genetic variation, mediated through transcriptional networks, can drive transient cell response phenotypes and contribute to organismal adaptative potential. PMID- 22053799 TI - [We shoot ourselves in the foot again]. PMID- 22053800 TI - [Notable increase in the consumption of antibiotics in general practice]. AB - The antimicrobial consumption in primary health care has increased notably during the latest decade. The increase has predominantly been among broad-spectrum antimicrobial agents. Denmark is no longer among the European countries with the lowest consumption. The reasons for these changes are not fully explained, but increased dosage for each treated patient and more patients treated have played an important role. To some extent, the consumption meets with relevant quality indicators for antibiotic prescribing, but the use of resistance inducing antibiotics needs to be limited according to guidelines. PMID- 22053801 TI - [Increasing antimicrobial consumption in hospitals]. AB - The antimicrobial consumption in hospital care has increased steadily during the latest decade. Now, broad-spectrum antimicrobial agents dominate the consumption at the expense of beta-lactamase sensitive penicillins. The reasons for these changes are not fully understood, but increased activity at the hospitals, higher resistance rates and the emergence of resistant nosocomial bacterial infections have played an important role. Denmark is no longer among the European countries with the lowest consumption. This indicates the need to implement restriction on antimicrobial usage in hospital care. PMID- 22053802 TI - [The development of antibiotics use in Danish food production]. AB - In the Danish husbandry antimicrobial growth promoters were phased out 1994-2000 and the therapeutic use has been increasingly regulated. Hitherto, a minimum in therapeutic use was reached in 1997. The antimicrobial use in pigs increased by 44% during 2002-2009; a 12% decrease in second half of 2010 was likely due to the announcement of the "yellow card" regulation. From July 2010, a voluntary two years stop of cephalosporins use in pigs was realized, due to increasing occurrence of extended spectrum beta lactamase (ESBL) resistance in animal and meat isolates; highest levels of ESBL are observed in imported poultry. PMID- 22053803 TI - [Still increasing incidence of MRSA and ESBL-producing Enterobacteriaceae in society and in hospital-associated cases]. AB - This review describes the recent epidemiology for MRSA and ESBL-producing Enterobacteriaceae in Denmark. MRSA community-associated cases continue to increase whereas hospital associated cases are low and stable. Due to an active search and destroy policy secondary transmission is modest. MRSA from pigs is an increasing problem. For ESBL producing Escherichia coli a considerable multi clonal increase has been seen both in the community and in hospitals. There are indications on food being a significant reservoir. For ESBL producing Klebsiella pneumoniae an increasing number of hospital outbreaks have been observed. PMID- 22053804 TI - [Rational antibiotic treatment can be achieved through audits and teaching]. AB - A prerequisite for rational antibiotic treatment is the suspicion that the disease is caused by bacteria and that treatment will reduce symptoms and complications. In primary health care most infections are caused by bacteria. The European project HAPPY AUDIT found that an intervention targeting doctors and patients in primary care led to a considerable decrease in antibiotic prescribing. Teaching of hospital doctors, combined with a restriction in the choice of antibiotics, resulted in a decrease in multidrug-resistant strains. A concerted effort is needed to curb the growing resistance problem. PMID- 22053805 TI - [Increasing antibiotic resistance: the prognostic impact has yet to be determined]. AB - The rising prevalence of multiresistant bacteria has become a major clinical concern. Yet, the prognostic impact is not well elucidated. A growing number of studies have found associations between acquired resistance, inappropriate therapy and mortality. The key underlying factors seem to be delay of appropriate antibiotic therapy and possibly use of more toxic therapy. However, methodological issues including control group selection and adjustment for potential confounders must be taken into consideration when assessing outcome studies for patients infected with resistant microorganisms. PMID- 22053806 TI - [The international surveillance of antibiotics resistance]. AB - The growth promoter story in the 1990 s increased the focus on antibiotic misuse and related resistance. A Danish EU conference, The Microbial Threat, in 1998 resulted in The Copenhagen Recommendations, on the basic principles for a policy to contain resistance, which was transformed into EU recommendations in 2001. Following this a range of programs on monitoring of resistance and consumption, research, national campaigns etc. has been accomplished. The US, Canada and Australia have also upgraded their efforts in this area, while the WHO lacks resources to approach the countries in the rest of the world, in which these problems are the worst. PMID- 22053807 TI - [Selection and spreading of antibiotic resistance in bacteria]. AB - Use of an antibiotic may not only select for resistance against the agent itself, but may at the same time co-select for resistance against other antibiotics if resistance genes are linked on e.g. a plasmid. Resistance plasmids may also carry genes mediating resistance against metals and disinfectants. Therefore, abundant use of metals, e.g. copper and zinc for growth promotion in animals used for food, may also co-select for antibiotic resistance. The same applies to disinfectants, e.g. silver and chlorhexidine. Prudent use of antibiotics and these other agents is essential to control antibiotic resistance. PMID- 22053808 TI - Traditional and proposed tests of slope homogeneity for non-normal and heteroscedastic data. AB - The purpose of this study was to develop and compare tests of independent groups' slopes for non-normal distributions and heteroscedastic variances, including slope tests based on least squares, Theil-Sen, and trimmed estimation approaches. A slope test based on jackknife standard error estimates is proposed that can utilize each of the traditional estimation methods while also addressing problematic aspects of methods' standard error estimates. Simulations demonstrate that the proposed jackknife-based slope tests can improve standard error estimation, Type I error, and power relative to the traditional slope tests. PMID- 22053809 TI - Kudzu (Pueraria lobata) vine ethanol extracts improve ovariectomy-induced bone loss in female mice. AB - Bone-loss-improving action of kudzu vine ethanol extracts (PVEE) was clarified. PVEE was composed roughly of 80% fiber, 10% puerarin, 3.6% daidzin, 2.5% 6"-O malonyldaidzin, and the other minor isoflavones. Ten-week-old ovariectomized (OVX) mice were fed diets containing PVEE (20 mg/kg body weight/day) for 8 weeks. The bone resorption markers (urinary deoxypyridinoline and tartrate-resistant acid phosphatase activity) was elevated in OVX mice and was significantly decreased in OVX mice that consumed PVEE for 8 weeks. Consistent with the decrease in the markers, the number of matured osteoclasts in the distal femur was diminished in OVX mice fed PVEE diets. PVEE diets also suppressed the decrease in femoral bone mineral density (BMD) by OVX. PVEE showed the affinity for estrogen receptor alpha and beta nearly 1/10000 weaker than 17beta-estradiol. No hypertrophy in the uterus by the PVEE diet was observed. These results suggest that PVEE could be a promising resource for a functional food that improves osteoporosis. PMID- 22053810 TI - Is it recorded in the notes? Documentation of end-of-life care and preferred place to die discussions in the final weeks of life. AB - BACKGROUND: Over the past ten years there has been an increasing focus on the need for improving the experience of end of life care. A number of policy initiatives have been introduced to develop approaches to discussing and documenting individual preferences for end of life care, in particular preferred place to die. METHODS: The aim was to investigate practice in relation to discussing and documenting end of life care and preferred place to die in the last 4 weeks of life with patients and their families. The study utilised an audit of 65 case notes, alongside four group interviews with a mix of health care professionals involved in palliative care provision. RESULTS: While there was evidence that discussions relating to end of life care and preferred place to die had taken place in around half of the audited case notes, there appeared to be a lack of a systematic approach to the recording of discussions with patients or carers about these kind of issues. Health care staff subsequently highlighted that initiating discussions about end of life care and preferences in relation to place of death was challenging and that the recording and tracking of such preferences was problematic. CONCLUSIONS: Further work is required to establish how information may be adequately recorded, revised and transferred across services to ensure that patients' preferences in relation to end of life care and place of death are, as far as possible, achieved. PMID- 22053812 TI - Low-molecular-mass antioxidants in parasites. AB - SIGNIFICANCE: Parasitic infections continue to be a major problem for global human health. Vaccines are practically not available and chemotherapy is highly unsatisfactory. One approach toward a novel antiparasitic drug development is to unravel pathways that may be suited as future targets. Parasitic organisms show a remarkable diversity with respect to the nature and functions of their main low molecular-mass antioxidants and many of them developed pathways that do not have a counterpart in their mammalian hosts. RECENT ADVANCES: Work of the last years disclosed the individual antioxidants employed by parasites and their distinct pathways. Entamoeba, Trichomonas, and Giardia directly use cysteine as main low molecular-mass thiol but have divergent cysteine metabolisms. Malarial parasites rely exclusively on cysteine uptake and generate glutathione (GSH) as main free thiol as do metazoan parasites. Trypanosomes and Leishmania have a unique trypanothione-based thiol metabolism but employ individual mechanisms for their cysteine supply. In addition, some trypanosomatids synthesize ovothiol A and/or ascorbate. Various essential parasite enzymes such as trypanothione synthetase and trypanothione reductase in Trypanosomatids and the Schistosoma thioredoxin GSH reductase are currently intensively explored as drug target molecules. CRITICAL ISSUES: Essentiality is a prerequisite but not a sufficient property of an enzyme to become a suited drug target. The availability of an appropriate in vivo screening system and many other factors are equally important. FUTURE DIRECTIONS: The current organism-wide RNA-interference and proteome analyses are supposed to reveal many more interesting candidates for future drug development approaches directed against the parasite antioxidant defense systems. PMID- 22053813 TI - Hydrogen peroxide-induced oxidation of mixtures of alkanethiols and their quantitative detection as alkanesulfonates by electrospray ionization mass spectrometry. AB - Finding optimal experimental conditions for generating stable negative ion electrospray ionization ion trap mass spectra (ESI-IT-MS) of alkanethiol-derived species is critical for quantitatively characterizing multicomponent alkanethiol based self-assembled monolayers by this technique. Since alkanethiolates slowly oxidize in solution, purposeful oxidation of alkanethiols to their fully oxidized form (alkanesulfonates) is advantageous: sulfonates are chemically stable and have little affinity for covalent binding to metal surfaces. We have used ESI-IT MS to characterize the products of H(2)O(2) oxidation of simple n-alkanethiols in solution and have observed monomeric alkanesulfonate species as well as alkanesulfonic acid/alkanesulfonate adducts, yielding gas-phase dimers and trimers. MS intensities of both monomers and adducts exhibit a dependence on the ion transfer capillary temperature that is alkyl-chain-length-dependent and that appears to be correlated with C-S bond cleavage. The trend in optimal capillary temperatures indicates that entropic effects lead to lower thermal decomposition temperatures for short-chain species relative to the longer-chain homologues. MS calibration data from alkanesulfonate mixtures are characterized by large linear dynamic ranges (10(-6)-10(-3) M) and detection limits influenced by their thermal decomposition. The high degree of precision in the calibration data should facilitate distinguishing among mixed SAMs having similar compositions. PMID- 22053814 TI - Semantic encoding enhances the pictorial superiority effect in the oldest-old. AB - ABSTRACT We examined the effect of a semantic orienting task during encoding on free recall and recognition of simple line drawings and matching words in middle aged (44-59 years), older (60-89 years), and oldest-old (90+ years) adults. Participants studied line drawings and matching words presented in blocked order. Half of the participants were given a semantic orienting task and the other half received standard intentional learning instructions. Results confirmed that the pictorial superiority effect was greater in magnitude following semantic encoding compared to the control condition. Analyses of clustering in free recall revealed that oldest-old adults' encoding and retrieval strategies were generally similar to the two younger groups. Self-reported strategy use was less frequent among the oldest-old adults. These data strongly suggest that semantic elaboration is an effective compensatory mechanism underlying preserved episodic memory performance that persists well into the ninth decade of life. PMID- 22053815 TI - Synthesis of the reported structure of trans-africanan-1alpha-ol. AB - A trisubstituted cyclopentane chiron has been prepared by dynamic kinetic reduction of a pulegone-derived beta-keto ester. This chiron served as the starting material for the synthesis of the reported structure of the tricyclic sesquiterpene trans-africanan-1alpha-ol. The synthetic material was not congruent with the natural product. PMID- 22053816 TI - Course trajectories of unipolar depressive disorders identified by latent class growth analysis. AB - BACKGROUND: Current classification of unipolar depression reflects the idea that prognosis is essential. However, do DSM categories of major depressive disorder (MDD), dysthymic disorder (Dysth) and double depression (DD=MDD+Dysth) indeed adequately represent clinically relevant course trajectories of unipolar depression? Our aim was to test DSM categories (MDD, Dysth and DD) in comparison with empirically derived prognostic categories, using a prospectively followed cohort of depressed patients. METHOD: A large sample (n=804) of out-patients with unipolar depression were derived from a prospective cohort study, the Netherlands Study of Depression and Anxiety (NESDA). Using latent class growth analysis (LCGA), empirically derived 2-year course trajectories were constructed. These were compared with DSM diagnoses and a wider set of putative predictors for class membership. RESULTS: Five course trajectories were identified, ranging from mild severity and rapid remission to high severity and chronic course trajectory. Contrary to expectations, more than 50% of Dysth and DD were allocated to classes with favorable course trajectories, suggesting that current DSM categories do not adequately represent course trajectories. The class with the most favorable course trajectory differed on several characteristics from other classes (younger age, more females, less childhood adversity, less somatic illnesses, lower neuroticism, higher extraversion). Older age, earlier age of onset and lower extraversion predicted poorest course trajectory. CONCLUSIONS: MDD, Dysth and DD did not adequately match empirically derived course trajectories for unipolar depression. For the future classification of unipolar depression, it may be wise to retain the larger, heterogeneous category of unipolar depression, adopting cross-cutting dimensions of severity and duration to further characterize patients. PMID- 22053817 TI - Structured expert elicitation about Listeria monocytogenes cross-contamination in the environment of retail deli operations in the United States. AB - Listeria monocytogenes is among the foodborne pathogens with the highest death toll in the United States. Ready-to-eat foods contaminated at retail are an important source of infection. Environmental sites in retail deli operations can be contaminated. However, commonly contaminated sites are unlikely to come into direct contact with food and the public health relevance of environmental contamination has remained unclear. To identify environmental sites that may pose a considerable cross-contamination risk, to elucidate potential transmission pathways, and to identify knowledge gaps, we performed a structured expert elicitation of 41 experts from state regulatory agencies and the food retail industry with practical experience in retail deli operations. Following the "Delphi" method, the elicitation was performed in three consecutive steps: questionnaire, review and discussion of results, second questionnaire. Hands and gloves were identified as important potential contamination sources. However, bacterial transfers to and from hands or gloves represented a major data gap. Experts agreed about transfer probabilities from cutting boards, scales, deli cases, and deli preparation sinks to product, and about transfer probabilities from floor drains, walk-in cooler floors, and knife racks to food contact surfaces. Comparison of experts' opinions to observational data revealed a tendency among experts with certain demographic characteristics and professional opinions to overestimate prevalence. Experts' votes clearly clustered into separate groups not defined by place of employment, even though industry experts may have been somewhat overrepresented in one cluster. Overall, our study demonstrates the value and caveats of expert elicitation to identify data gaps and prioritize research efforts. PMID- 22053818 TI - Donor age-specific injury and immune responses. AB - Utilization rates of organs from elderly donors have shown the highest proportional increase during the last decade. Clinical reports support the concept of transplanting older organs. However, the engraftment of such organs has been linked to accelerated immune responses based on ageing changes per se and a proinflammatory environment subsequent to compromised injury and repair mechanism. We analyzed the clinical consequences of transplanting older donor organs and present mechanistic aspects correlating age, injury repair and effects on host immunoresponsiveness. PMID- 22053819 TI - Nuclear targeting dynamics of gold nanoclusters for enhanced therapy of HER2+ breast cancer. AB - Recent advances in fluorescent metal nanoclusters have spurred tremendous interest in nanomedicine due to the ease of fabrication, excellent biocompatibility, and, more importantly, excellent wavelength-dependent tunability. Herein, we report our findings on fluorescent BSA-protected gold nanoclusters (AuNCs), ~2 nm in size conjugated with Herceptin (AuNCs-Her), for specific targeting and nuclear localization in ErbB2 over-expressing breast cancer cells and tumor tissue as a novel fluorescent agent for simultaneous imaging and cancer therapy. More interestingly, we found that AuNCs-Her could escape the endolysosomal pathway and enter the nucleus of cancer cells to enhance the therapeutic efficacy of Herceptin. We elucidate the diffusion characteristics (diffusion time and number of diffusers) and concentration of the fluorescing clusters in the nucleus of live cells. Our findings also suggest that the nuclear localization effect of AuNCs-Her enhances the anticancer therapeutic efficacy of Herceptin as evidenced by the induction of DNA damage. This study not only discusses a new nanomaterial platform for nuclear delivery of drugs but also provides important insights on nuclear targeting for enhanced therapy. PMID- 22053820 TI - Sputum proteomics identifies elevated PIGR levels in smokers and mild-to-moderate COPD. AB - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality around the world. However, the exact mechanisms leading to COPD and its progression are still poorly understood. In this study, induced sputum was analyzed by cysteine-specific two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry to identify proteins involved in COPD pathogenesis. The comparison of nonsmokers, smokers, and smokers with moderate COPD revealed 15 changed proteins with the majority, including polymeric immunoglobulin receptor (PIGR), being elevated in smokers and subjects with COPD. PIGR, which is involved in specific immune defense and inflammation, was further studied in sputum, lung tissue, and plasma by Western blot, immunohistochemistry/image analysis, and/or ELISA. Sputum PIGR was characterized as glycosylated secretory component (SC). Lung PIGR was significantly elevated in the bronchial and alveolar epithelium of smokers and further increased in the alveolar area in mild to moderate COPD. Plasma PIGR was elevated in smokers and smokers with COPD compared to nonsmokers with significant correlation to obstruction. In conclusion, new proteins in smoking-related chronic inflammation and COPD could be identified, with SC/PIGR being one of the most prominent not only in the lung but also in circulating blood. PMID- 22053822 TI - Long-term functional outcome after restorative proctocolectomy in patients with ulcerative colitis. AB - AIM: The aim of this study was to evaluate the long-term functional outcome of ileal pouch-anal anastomosis for ulcerative colitis and to compare symptoms over time. METHODS: In all, 188 patients were operated with an ileal pouch-anal anastomosis. Short-term functional outcome has previously been evaluated with a symptom questionnaire. The same questionnaire was sent to the 162 patients who were alive and had an intact pouch. A symptom index was studied over time and in relation to early complications and pouchitis. RESULTS: The response rate of the questionnaire was 139/162 at a median of 12.5 (9.5-21) years postoperatively. Overall, the symptom index remained unchanged over time but both the frequency of night-time defaecation and episodes of night-time incontinence increased. Patients' global assessment was unchanged with approximately 80% stating an excellent or a good result. Frequency of pouchitis doubled in 10 years. Symptom index for patients with episodic pouchitis [median 40 (8-89), P = 0.018] and recurrent/chronic pouchitis [71 (8-136), P < 0.001] was higher than in patients without pouchitis [29 (0-105)]. Early complications did not affect the symptom index. CONCLUSION: The overall functional outcome of ileal pouch-anal surgery for ulcerative colitis is stable over time. Patients' satisfaction with outcome remains high. Pouchitis is a determinant of functional outcome. PMID- 22053821 TI - Trinuclear ruthenium clusters as bivalent electrochemical probes for ligand receptor binding interactions. AB - Despite their popularity, electrochemical biosensors often suffer from low sensitivity. One possible approach to overcome low sensitivity in protein biosensors is to utilize multivalent ligand-receptor interactions. Controlling the spatial arrangement of ligands on surfaces is another crucial aspect of electrochemical biosensor design. We have synthesized and characterized five biotinylated trinuclear ruthenium clusters as potential new biosensor platforms: [Ru(3)O(OAc)(6)CO(4-BMP)(py)](0) (3), [Ru(3)O(OAc)(6)CO(4-BMP)(2)](0) (4), [Ru(3)O(OAc)(6)L(4-BMP)(py)](+) (8), [Ru(3)O(OAc)(6)L(4-BMP)(2)](+) (9), and [Ru(3)O(OAc)(6)L(py)(2)](+) (10) (OAc = acetate, 4-BMP = biotin aminomethylpyridine, py = pyridine, L = pyC16SH). HABA/avidin assays and isothermal titration calorimetry were used to evaluate the avidin binding properties of 3 and 4. The binding constants were found to range from (6.5-8.0) * 10(6) M(-1). Intermolecular protein binding of 4 in solution was determined by native gel electrophoresis. QM, MM, and MD calculations show the capability for the bivalent cluster, 4, to intramolecularly bind to avidin. Electrochemical measurements in solution of 3a and 4a show shifts in E(1/2) of -58 and -53 mV in the presence of avidin, respectively. Self-assembled monolayers formed with 8-10 were investigated as a model biosensor system. Diluent/cluster ratio and composition were found to have a significant effect on the ability of avidin to adequately bind to the cluster. Complexes 8 and 10 showed negligible changes in E(1/2), while complex 9 showed a shift in E(1/2) of -43 mV upon avidin addition. These results suggest that multivalent interactions can have a positive impact on the sensitivity of electrochemical protein biosensors. PMID- 22053823 TI - HMGA1 drives stem cell, inflammatory pathway, and cell cycle progression genes during lymphoid tumorigenesis. AB - BACKGROUND: Although the high mobility group A1 (HMGA1) gene is widely overexpressed in diverse cancers and portends a poor prognosis in some tumors, the molecular mechanisms that mediate its role in transformation have remained elusive. HMGA1 functions as a potent oncogene in cultured cells and induces aggressive lymphoid tumors in transgenic mice. Because HMGA1 chromatin remodeling proteins regulate transcription, HMGA1 is thought to drive malignant transformation by modulating expression of specific genes. Genome-wide studies to define HMGA1 transcriptional networks during tumorigenesis, however, are lacking. To define the HMGA1 transcriptome, we analyzed gene expression profiles in lymphoid cells from HMGA1a transgenic mice at different stages in tumorigenesis. RESULTS: RNA from lymphoid samples at 2 months (before tumors develop) and 12 months (after tumors are well-established) was screened for differential expression of > 20,000 unique genes by microarray analysis (Affymetrix) using a parametric and nonparametric approach. Differential expression was confirmed by quantitative RT-PCR in a subset of genes. Differentially expressed genes were analyzed for cellular pathways and functions using Ingenuity Pathway Analysis. Early in tumorigenesis, HMGA1 induced inflammatory pathways with NFkappaB identified as a major node. In established tumors, HMGA1 induced pathways involved in cell cycle progression, cell-mediated immune response, and cancer. At both stages in tumorigenesis, HMGA1 induced pathways involved in cellular development, hematopoiesis, and hematologic development. Gene set enrichment analysis showed that stem cell and immature T cell genes are enriched in the established tumors. To determine if these results are relevant to human tumors, we knocked-down HMGA1 in human T-cell leukemia cells and identified a subset of genes dysregulated in both the transgenic and human lymphoid tumors. CONCLUSIONS: We found that HMGA1 induces inflammatory pathways early in lymphoid tumorigenesis and pathways involved in stem cells, cell cycle progression, and cancer in established tumors. HMGA1 also dyregulates genes and pathways involved in stem cells, cellular development and hematopoiesis at both early and late stages of tumorigenesis. These results provide insight into HMGA1 function during tumor development and point to cellular pathways that could serve as therapeutic targets in lymphoid and other human cancers with aberrant HMGA1 expression. PMID- 22053824 TI - Surface contact stimulates the just-in-time deployment of bacterial adhesins. AB - The attachment of bacteria to surfaces provides advantages such as increasing nutrient access and resistance to environmental stress. Attachment begins with a reversible phase, often mediated by surface structures such as flagella and pili, followed by a transition to irreversible attachment, typically mediated by polysaccharides. Here we show that the interplay between pili and flagellum rotation stimulates the rapid transition between reversible and polysaccharide mediated irreversible attachment. We found that reversible attachment of Caulobacter crescentus cells is mediated by motile cells bearing pili and that their contact with a surface results in the rapid pili-dependent arrest of flagellum rotation and concurrent stimulation of polar holdfast adhesive polysaccharide. Similar stimulation of polar adhesin production by surface contact occurs in Asticcacaulis biprosthecum and Agrobacterium tumefaciens. Therefore, single bacterial cells respond to their initial contact with surfaces by triggering just-in-time adhesin production. This mechanism restricts stable attachment to intimate surface interactions, thereby maximizing surface attachment, discouraging non-productive self-adherence, and preventing curing of the adhesive. PMID- 22053825 TI - Resolution of leucocyte-mediated mucosal diseases. A novel in vivo paradigm for drug development. AB - Removal of disease-driving inflammatory leucocytes is central to resolution of inflammation. The current pharmacological dogma teaches leucocyte elimination through apoptosis followed by phagocytosis. However, actual resolving roles of apoptotic-phagocytic processes have been difficult to demonstrate in the major diseases that are characterized by mucosal tissue inflammation. Many current in vivo observations rather demonstrate that leucocyte elimination occurs by transepithelial locomotion. Findings in diseased gut and bladder mucosae support this notion. Respiratory disease data are particularly compelling. Eosinophils and neutrophils abound in sputum and tracheal aspirates during treatment-induced recovery from severe asthma. Prolonged sputum neutrophilia, along with clinical improvement, follows upon smoking cessation in COPD. Eosinophils, neutrophils, lymphocytes, mast cells and dendritic cells also move in large numbers into the bronchial lumen at spontaneous inflammation resolution following allergen challenge in allergic rhinitis and asthma. A corresponding reduction of infiltrated cells in the bronchial mucosal tissue demonstrates efficiency of the transepithelial elimination pathway. Underscoring its operational role, drugs impeding transepithelial elimination of leucocytes aggravate mucosal/parenchymal inflammation. Hence, relying on lumen cell data alone can lead to paradoxical conclusions regarding anti-inflammatory drug efficacy. Conversely, drugs promoting non-injurious transepithelial elimination of leucocytes could resolve mucosal inflammatory diseases. PMID- 22053826 TI - Evaluating the catalytic contribution from the oxyanion hole in ketosteroid isomerase. AB - Prior site-directed mutagenesis studies in bacterial ketosteroid isomerase (KSI) reported that substitution of both oxyanion hole hydrogen bond donors gives a 10(5)- to 10(8)-fold rate reduction, suggesting that the oxyanion hole may provide the major contribution to KSI catalysis. But these seemingly conservative mutations replaced the oxyanion hole hydrogen bond donors with hydrophobic side chains that could lead to suboptimal solvation of the incipient oxyanion in the mutants, thereby potentially exaggerating the apparent energetic benefit of the hydrogen bonds relative to water-mediated hydrogen bonds in solution. We determined the functional and structural consequences of substituting the oxyanion hole hydrogen bond donors and several residues surrounding the oxyanion hole with smaller residues in an attempt to create a local site that would provide interactions more analogous to those in aqueous solution. These more drastic mutations created an active-site cavity estimated to be ~650 A(3) and sufficient for occupancy by 15-17 water molecules and led to a rate decrease of only ~10(3)-fold for KSI from two different species, a much smaller effect than that observed from more traditional conservative mutations. The results underscore the strong context dependence of hydrogen bond energetics and suggest that the oxyanion hole provides an important, but moderate, catalytic contribution relative to the interactions in the corresponding solution reaction. PMID- 22053828 TI - Insomnia as a risk for depression: a longitudinal epidemiologic study on a Japanese rural cohort. AB - OBJECTIVES: To determine (1) whether insomnia is a factor related to the presence or persistence of depression for 2 years in the Japanese population and (2) which component of insomnia is associated with the presence of depression for 2 years in a rural cohort. METHOD: This is a community-based longitudinal study. Two thousand eight hundred twenty-five people aged 20 years or older were evaluated at baseline, and of those participants, 1,577 (56%) were reevaluated after 2 years. During both surveys, the participants were asked to describe demographic variables and to fill out self-rating scales of insomnia (Pittsburgh Sleep Quality Index [PSQI]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale). RESULTS: The results of a multiple logistic regression analysis showed that depression (OR = 6.0; 95% CI, 4.4-8.0) and insomnia (OR = 2.1; 95% CI, 1.5-2.8) at baseline were significantly associated with the presence of depression at the follow-up. Most of the PSQI subscales, except for sleep duration and habitual sleep efficiency, were significantly associated (P < .01) with the presence of depression at the follow-up. In addition, the new appearance and repeated existence of depression at the follow-up were related to persistent insomnia (adjusted ORs = 7.0 and 3.3 [P < .001], respectively). A result of the receiver operating characteristic curve showed that persons with insomnia whose PSQI scores exceeded 8 points at the baseline were most likely to still have insomnia at the follow-up (cutoff point = 7.5). CONCLUSIONS: On the basis of our results in a Japanese population, insomnia with high severity level could be a risk factor for the presence/persistence of depression in the long-term prognosis. PMID- 22053827 TI - Construction and characterisation of a recombinant fowlpox virus that expresses the human papilloma virus L1 protein. AB - BACKGROUND: Human papilloma virus (HPV)-16 is the most prevalent high-risk mucosal genotype. Virus-like-particle (VLP)-based immunogens developed recently have proven to be successful as prophylactic HPV vaccines, but are still too expensive for developing countries. Although vaccinia viruses expressing the HPV 16 L1 protein (HPV-L1) have been studied, fowlpox-based recombinants represent efficient and safer vectors for immunocompromised hosts due to their ability to elicit a complete immune response and their natural host-range restriction to avian species. METHODS: A new fowlpox virus recombinant encoding HPV-L1 (FPL1) was engineered and evaluated for the correct expression of HPV-L1 in vitro, using RT-PCR, immunoprecipitation, Western blotting, electron microscopy, immunofluorescence, and real-time PCR assays. RESULTS: The FPL1 recombinant correctly expresses HPV-L1 in mammalian cells, which are non-permissive for the replication of this vector. CONCLUSION: This FPL1 recombinant represents an appropriate immunogen for expression of HPV-L1 in human cells. The final aim is to develop a safe, immunogenic, and less expensive prophylactic vaccine against HPV. PMID- 22053829 TI - Control of ice chromatographic retention mechanism by changing temperature and dopant concentration. AB - A liquid phase coexists with solid water ice in a typical binary system, such as NaCl-water, in the temperature range between the freezing point and the eutectic point (t(eu)) of the system. In ice chromatography with salt-doped ice as the stationary phase, both solid and liquid phase can contribute to solute retention in different fashions; that is, the solid ice surface acts as an adsorbent, while a solute can be partitioned into the liquid phase. Thus, both adsorption and partition mechanisms can be utilized for ice chromatographic separation. An important feature in this approach is that the liquid phase volume can be varied by changing the temperature and the concentration of a salt incorporated into the ice stationary phase. Thus, we can control the relative contribution from the partition mechanism in the entire retention because the liquid phase volume can be estimated from the freezing depression curve. Separation selectivity can thereby be modified. The applicability of this concept has been confirmed for the solutes of different adsorption and partition abilities. The predicted retention based on thermodynamics basically agrees well with the corresponding experimental retention. However, one important inconsistency has been found. The calculation predicts a step-like discontinuity of the solute retention at t(eu) because the phase diagram suggests that the liquid phase abruptly appears at t(eu) when the temperature increases. In contrast, the corresponding experimental plots are continuous over the wider range including the subeutectic temperatures. This discrepancy is explained by the existence of the liquid phase below t(eu). A difference between predicted and measured retention factors allows the estimation of the volume of the subeutectic liquid phase. PMID- 22053831 TI - The 2011 Nobel Prize in physiology or medicine. AB - The 2011 Noble Prize in Physiology or Medicine was awarded to Bruce A. Beutler, Jules A. Hoffmann and Ralph M. Steinman for their groundbreaking research within immunology. Bruce A. Beutler and Jules A. Hoffmann were recognized for their discoveries on Toll and Toll-like receptor activation of innate immunity in fruit fly and mammals, respectively. Ralph M. Steinman received the award for the discovery of dendritic cells, a cell type bridging innate and adaptive immunity, and how these cells orchestrate immune responses. PMID- 22053830 TI - Correlation between DNA ploidy, metaphase high-resolution comparative genomic hybridization results and clinical outcome of synovial sarcoma. AB - BACKGROUND: Although synovial sarcoma is the 3rd most commonly occurring mesenchymal tumor in young adults, usually with a highly aggressive clinical course; remarkable differences can be seen regarding the clinical outcome. According to comparative genomic hybridization (CGH) data published in the literature, the simple and complex karyotypes show a correlation between the prognosis and clinical outcome. In addition, the connection between DNA ploidy and clinical course is controversial. The aim of this study was using a fine tuning interpretation of our DNA ploidy results and to compare these with metaphase high-resolution CGH (HR-CGH) results. METHODS: DNA ploidy was determined on Feulgen-stained smears in 56 synovial sarcoma cases by image cytometry; follow up was available in 46 cases (average: 78 months). In 9 cases HR-CGH analysis was also available. RESULTS: 10 cases were found DNA-aneuploid, 46 were DNA-diploid by image cytometry. With fine-tuning of the diploid cases according to the 5c exceeding events (single cell aneuploidy), 33 cases were so called "simple-diploid" (without 5c exceeding events) and 13 cases were "complex diploid"; containing 5c exceeding events (any number). Aneuploid tumors contained large numbers of genetic alterations with the sum gain of at least 2 chromosomes (A-, B- or C-group) detected by HR-CGH. In the "simple-diploid" cases no or few genetic alterations could be detected, whereas the "complex-diploid" samples numerous aberrations (equal or more than 3) could be found. CONCLUSIONS: Our results show a correlation between the DNA-ploidy, a fine-tuned DNA-ploidy and the HR-CGH results. Furthermore, we found significant correlation between the different ploidy groups and the clinical outcome (p < 0.05). PMID- 22053832 TI - Use of the Case Western Reserve/Veterans Administration neuroprosthesis for exercise, standing and transfers by a paraplegic subject. AB - Functional electric stimulation (FES) is a technology that may allow patients with spinal cord injury (SCI) to transfer stand and walk. This paper reports upon the use of the Case Western Reserve Neuroprosthesis by a T6 ASIA B paraplegic subject. The subject was able to stand for two minutes and 50 seconds. He could walk 35 feet with a swing to gait. Measurement of energy consumption showed that metabolic demand was only 2.1 metabolic equivalent units. The factors that limited the use of the device that need to be improved to make the technology practical for household or community ambulation are speed (5.8 m/min) of ambulation and fatigue of the stimulated muscles. PMID- 22053833 TI - Is bilateral age-related macular degeneration less common in Asians than Caucasians? AB - PURPOSE: To compare the frequency and pattern of bilateral involvement of early and late age-related macular degeneration (AMD) between Asian Malays and Caucasians. METHODS: We used cross-sectional data from the baseline examination for subjects aged 50-79 years in the Singapore Malay Eye Study (SiMES) (N = 2,453) and the Blue Mountains Eye Study (BMES) (N = 3,265). We assessed AMD signs using a common protocol modified from the Wisconsin Age-related Maculopathy Grading System at the University of Sydney. We compared frequencies or proportions of AMD cases with bilateral involvement between the two populations. RESULTS: There were 173 cases and 169 cases with any AMD (either early or late AMD in at least one eye), and 78 cases (45.1%) and 52 cases (30.8%) with bilateral AMD in the BMES and the SiMES, respectively. Age-standardized frequency of bilateral involvement was comparable between the BMES (29.5%, 95% confidence interval(CI) 18.5-40.5%) and the SiMES (25.6%, 95%CI 17.0-34.0%). Older age was associated with higher risk of bilateral AMD (gender-adjusted odds ratio per 1 year for the BMES and the SiMES: 1.08 [95% CI 1.05-1.11] and 1.06 [95% CI 1.02 1.10], respectively). CONCLUSIONS: The frequency of bilateral AMD was comparable between Asian Malays in the SiMES and the Caucasian population of the BMES. Other than older age, we did not find any characteristics associated with the bilateral involvement of AMD. PMID- 22053834 TI - Chronic kidney disease, early age-related macular degeneration, and peripheral retinal drusen. AB - PURPOSE: To evaluate the association between chronic kidney disease (CKD) and early age-related macular degeneration (AMD) and peripheral retinal drusen in Korean adults 50 years and older. METHODS: This study included 3008 participants aged 50-87 years. Early AMD was assessed from retinal photographs based on modified Wisconsin AMD grading system and peripheral retinal drusen were assessed with a standardized examination. We defined CKD as estimated glomerular filtration rate of 60mL/min/1.73m(2) and below according to the Modification of Diet in Renal Disease equation. Logistic regression was used to examine the association between early AMD, peripheral retinal drusen, and CKD. RESULTS: There were 88 subjects with early AMD and 42 subjects with peripheral retinal drusen. After adjusting for age, gender, body mass index, smoking status, hypertension, and diabetes mellitus, a significant association was found between CKD and peripheral retinal drusen as well as early AMD. Subjects with CKD were more likely to have early AMD (OR, 1.68; 95% CI, 1.04-2.72) and peripheral retinal drusen (OR, 2.01; 95% CI, 1.02-3.99) than those without CKD. CONCLUSIONS: CKD was associated with peripheral retinal drusen as well as early AMD in Korean adults 50 years and older. PMID- 22053835 TI - The utility of non-ophthalmologist examination of eyes at risk for serious retinopathy of prematurity. AB - BACKGROUND: Retinopathy of Prematurity (ROP) is the main cause of preventable blindness in premature babies. Currently, there is a shortage of trained ophthalmologists, which has resulted in an alarming increase in cases of vision loss and related complications. This study's aim was to determine the utility of examinations conducted by non-ophthalmologist physicians to assess posterior pole vessel abnormalities in eyes at risk for ROP. METHOD: Non-ophthalmologist physicians (pediatrician and neonatologist) were trained to use an indirect ophthalmoscope to view the posterior pole of babies at risk for ROP. Examinations were conducted on both eyes of premature infants born before 35 weeks gestational age (GA) starting at the third week after birth and weekly thereafter. The presence of Plus disease was identified by the non-ophthalmologist and results compared to the clinical examination by a pediatric ophthalmologist experienced in ROP detection and treatment. Chi-square was used for proportions and the Mann Whitney U test for medians. Fagan's nomogram was determined for diagnostic usability. The Kappa index was used to rate inter-observer agreement. RESULTS: Results of 228 examinations performed on 150 premature infants were analyzed to determine the correlation of the non-ophthalmologist findings and the eye examination. For any vascular change in posterior pole diagnostic, findings were 87% and 87% accuracy for pediatrician and neonatologist, 82% and 83% sensitivity, 90% and 90% specificity respectively. There was no significant difference found in the detection of Plus disease for the examinations performed by the ophthalmologist compared to those performed by the non-ophthalmologist (P < 0.05). CONCLUSIONS: After training in the use of an indirect ophthalmoscope, non ophthalmologist physicians can reliably detect posterior pole retinal vessel changes for ROP diagnosis. PMID- 22053836 TI - Screening for retinopathy of prematurity in a large tertiary neonatal intensive care unit in Turkey: frequency and risk factors. AB - PURPOSE: We aimed to determine applicable guidelines for screening of retinopathy of prematurity (ROP), and evaluate the contribution of risk factors for severe ROP. METHODS: A prospective cohort study of neonates with a gestational age (GA) < 34 weeks or birth weight < 2000g who were admitted to the Neonatal Intensive Care Unit (NICU) of a tertiary level hospital was conducted. The study group was classified into three groups according to eye examination findings as no ROP, mild ROP and severe ROP. RESULTS: Of the 700 neonates screened, the frequencies of ROP for any stage and severe ROP were 32.7% and 3.1%, respectively. Laser photocoagulation was needed in 9.6% of neonates with ROP. None of the neonates with a GA >= 31 weeks required treatment. Any ROP was detected in 199 (53.6%) of the babies < 32 weeks (n = 371), 22 (5.9%) of whom were treated with laser photocoagulation. Independent risk factors for severe ROP in babies < 32 weeks GA were birth weight, duration of mechanical ventilation and patent ductus arteriosus (PDA). CONCLUSION: This is the largest prospective cohort study including infants younger than 34 weeks GA from Turkey. Our data which belongs to the last 1-year period shows lower incidence of severe ROP when compared to previous reports from Turkey. According to our data, screening babies smaller than 32 weeks GA or 1500g birth weight seems reasonable. In the presence of long duration of mechanical ventilation and PDA, screening should be intensified. PMID- 22053837 TI - Retinal vessel caliber and myopic retinopathy: the blue mountains eye study. AB - PURPOSE: To evaluate changes in the retinal vasculature in eyes with myopic retinopathy. METHODS: Population-based, cross-sectional study. Emmetropic and myopic participants from the Blue Mountains Eye Study baseline survey were included in this study. Myopia was defined as a refractive error of less than 1.00 diopter. Myopic retinopathy was defined if either staphyloma, lacquer crack, Fuchs' spot or chorioretinal atrophy were present in myopic eyes. Retinal vascular caliber was measured from fundus photographs using standardized methods. The association of retinal vascular caliber with myopic retinopathy was assessed using generalized estimating equation models. RESULTS: A total of 2598 eyes of 1409 subjects were selected from 3654 baseline participants, with 2076 emmetropic eyes (normal controls), 486 myopic eyes without myopic retinopathy (myopic controls) and 36 myopic eyes with myopic retinopathy (cases). After adjusting for age, gender, height, body mass index and blood pressure, eyes with myopic retinopathy had significantly narrower mean arteriolar (166.6MUm) and venular caliber (213.3MUm), compared to normal (188.1MUm and 226.9MUm, respectively) or myopic control eyes (190.4MUm and 227.0MUm, respectively) (all P < 0.001). These retinal vessel caliber differences between myopic retinopathy and the two control groups remained significant after additional adjustment for refraction (all P < 0.001). CONCLUSIONS: Our findings suggest that myopic retinopathy is associated with attenuation of retinal vessels. PMID- 22053838 TI - The prevalence and risk factors of ocular trauma: the Singapore Indian eye study. AB - PURPOSE: To describe the prevalence and risk factors of ocular trauma in an urban Southeast Asian population. METHODS: A population-based survey of 3,400 (75.6% response rate) adults of Indian ethnicity aged 40-80 years residing in Singapore was conducted in 2007-2009. An age-stratified (10-year age group) random sampling procedure was performed to select participants. Ocular trauma was defined as any eye injury requiring medical attention and any history of ocular trauma was documented using a standardized and validated questionnaire comprising seven questions. Potential risk factors associated with ocular trauma included age, gender, socioeconomic status, occupation, housing type, alcohol consumption, smoking, diabetes mellitus, hypertension and history of falls. RESULTS: Ocular trauma was reported in 5.1% (n = 162; 95% confidence interval [CI] 4.3-6.1%) of the study population, of whom 26.5% (n = 43) required hospitalization. A total of 42.0% (n = 68) of cases resulted from a blunt object, 36.4% (n = 59) from a sharp object, and 15.4% (n = 25) from chemical burns. After adjusting for age and sex, men had a higher prevalence of ocular trauma (7.1% vs. 3.0%, age-adjusted odds ratio [OR] 2.2, 95% CI 1.6-3.1). A history of cigarette smoking was associated with higher likelihood of ocular trauma (OR 1.6, 95% CI 1.1-2.4) but not consumption of alcohol (OR 1.0, 95% CI 0.6-1.6). CONCLUSIONS: One in twenty Indian adults in this urban Southeast Asian population had a history of ocular trauma, similar to the prevalence reported in Malays living in Singapore. Men and cigarette smokers were more likely to have incurred ocular trauma. PMID- 22053839 TI - Serum retinol and xerophthalmia among a prison population in Papua New Guinea. AB - PURPOSE: To estimate the prevalence of vitamin A deficiency (VAD) and one of its clinical manifestations, xerophthalmia, and examine the predictive value of nyctalopia and ocular signs for serum retinol concentrations among a prison population in Papua New Guinea. METHODS: A cross-sectional study of 148 prisoners and 9 guards; all males aged >=18 years. Interview-based questionnaire; ocular examination; serum retinol concentration determination. RESULTS: Two guards had marginal (retinol <1.05->=0.70 umol/L) VAD. For prisoners: mean retinol was 0.84 +/- 0.49 umol/L; 43.9% (95% CI 35.9, 52.2) had VAD (retinol <0.70 umol/L); 9.6% (95% CI 5.1, 17.0) self-reported nyctalopia prior to, and 36.1% (95% CI 27.7, 45.5) after incarceration; 10.9% (95% CI 6.7, 17.0) exhibited at least one sign of xerophthalmia (2 had fundus changes; all 4 with more than conjunctival xerosis alone had severe [<0.35 umol/L] retinol deficiency). Prisoners with ocular signs were more likely than those without to have VAD (OR 10.4; 95% CI 2.5, 70.3; P < 0.001) and severe retinol deficiency (OR 19.1; 95% CI 5.5, 77.2; P < 0.001). Positive (PPV) and Negative (NPV) Predictive Values: of nyctalopia for any (PPV 62.9%; NPV 32.8%) and severe (PPV 25.7%; NPV 85.9%) retinol deficiency; of ocular signs for any (PPV 93.3%; NPV 38.2%) and severe (PPV 73.1%; NPV 87.8%) retinol deficiency, and VAD (PPV 86.5%, NPV 38.2%). CONCLUSIONS: VAD and xerophthalmia were present in this prison population. There may be VAD in the wider community. The former needs remedy and the latter deserves investigation. Self-reported nyctalopia was not a useful indicator of retinol deficiency. Absence of ocular signs was unhelpful for ruling out VAD. PMID- 22053840 TI - Iron oxide nanoparticle-induced epidermal growth factor receptor expression in human stem cells for tumor therapy. AB - Superparamagnetic iron oxide (SPIO) nanoparticles show promise as labels for cellular magnetic resonance imaging (MRI) in the application of stem cell-based therapy. However, the unaddressed concerns about the impact of SPIO nanoparticles on stem cell attributes make the feasibility of SPIO labeling uncertain. Here, we show that the labeling of human mesenchymal stem cells (hMSCs) with ferucarbotran can induce epidermal growth factor receptor (EGFR) overexpression. Labeled hMSCs with their overexpressed EGFR were attracted by tumorous EGF and more effectively migrated toward tumor than unlabeled cells, resulting in more potent intrinsic antitumor activity. Moreover, the captured binding of tumorous EGF by overexpressed EGFR of labeled hMSCs blocked EGF/EGFR signaling-derived tumor growth, tumorous angiogenesis, and tumorous VEGF expression also responsible for tumor progression and development. Our results show that the impact of SPIO nanoparticles on stem cell attributes is not necessarily harmful but can be cleverly used to be beneficial to stem cell-based therapy. PMID- 22053844 TI - Metabolomics study on the toxicity of aconite root and its processed products using ultraperformance liquid-chromatography/electrospray-ionization synapt high definition mass spectrometry coupled with pattern recognition approach and ingenuity pathways analysis. AB - The mother and lateral root of Aconitum carmichaelii Debx, named "Chuanwu" (CW) and "Fuzi", respectively, has been used to relieve joint pain and treat rheumatic diseases for over 2000 years. However, it has a very narrow therapeutic range, and the toxicological risk of its usage remains very high. The traditional Chinese processing approach, Paozhi (detoxifying measure),can decompose poisonous Aconitum alkaloids into less or nontoxic derivatives and plays an important role in detoxification. The difference in metabolomic characters among the crude and processed preparations is still unclear, limited by the lack of sensitive and reliable biomarkers. Therefore, this paper was designed to investigate comprehensive metabolomic characters of the crude and its processed products by UPLC-Q-TOF-HDMS combined with pattern recognition methods and ingenuity pathway analysis (IPA). The significant difference in metabolic profiles and changes of metabolite biomarkers of interest between the crude and processed preparations were well observed. The underlying regulations of Paozhi-perturbed metabolic pathways are discussed according to the identified metabolites, and four metabolic pathways are identified using IPA. The present study demonstrates that metabolomic analysis could greatly facilitate and provide useful information to further comprehensively understand the pharmacological activity and potential toxicity of processed Aconite roots in the clinic. PMID- 22053845 TI - Redox regulation in photosynthetic organisms: focus on glutathionylation. AB - SIGNIFICANCE: In photosynthetic organisms, besides the well-established disulfide/dithiol exchange reactions specifically controlled by thioredoxins (TRXs), protein S-glutathionylation is emerging as an alternative redox modification occurring under stress conditions. This modification, consisting of the formation of a mixed disulfide between glutathione and a protein cysteine residue, can not only protect specific cysteines from irreversible oxidation but also modulate protein activities and appears to be specifically controlled by small disulfide oxidoreductases of the TRX superfamily named glutaredoxins (GRXs). RECENT STUDIES: In recent times, several studies allowed significant progress in this area, mostly due to the identification of several plant proteins undergoing S-glutathionylation and to the characterization of the molecular mechanisms and the proteins involved in the control of this modification. CRITICAL ISSUES: This article provides a global overview of protein glutathionylation in photosynthetic organisms with particular emphasis on the mechanisms of protein glutathionylation and deglutathionylation and a focus on the role of GRXs. Then, we describe the methods employed for identification of glutathionylated proteins in photosynthetic organisms and review the targets and the possible physiological functions of protein glutathionylation. FUTURE DIRECTIONS: In order to establish the importance of protein S-glutathionylation in photosynthetic organisms, future studies should be aimed at delineating more accurately the molecular mechanisms of glutathionylation and deglutathionylation reactions, at identifying proteins undergoing S-glutathionylation in vivo under diverse conditions, and at investigating the importance of redoxins, GRX, and TRX, in the control of this redox modification in vivo. PMID- 22053846 TI - End point prick test: could this new test be used to predict the outcome of oral food challenge in children with cow's milk allergy? AB - BACKGROUND: Cow's milk allergy (CMA) is the most frequent food allergy in childhood; the trend of CMA is often characterized by a progressive improvement to achieve tolerance in the first 4 to 5 years of life.It has been observed that specific IgE (sIgE) towards cow's milk proteins decrease when the age increases.Although food allergy can be easily diagnosed, it is difficult to predict the outcome of the oral food challenge (OFC), that remains the gold standard in the diagnosis of food allergy, by allergometric tests. METHODS: We considered 44 children with CMA diagnosed through OFC who returned to our Allergy and Immunology Pediatric Department between January to December 2010 to evaluate the persistence of allergy or the achievement of tolerance.On the basis of the history, we performed both allergometric skin tests and OFC in children that were still following a milk-free diet, whereas only allergometric skin tests those that had already undergone spontaneous introduction of milk protein at home without presenting symptoms. OBJECTIVE: The aim of this study was to investigate the relationship between the persistence of CMA or the acquisition of tolerance and the results of the end point prick test (EPT). RESULTS AND DISCUSSION: The OFC with cow's milk was performed on 30 children, 4 children were excluded because of a history of severe reactions to cow's milk, and 10 because they had spontaneously already taken milk food derivates at home without problems. 16/30 (53%) children showed clinical reactions and the challenge was stopped, 14/30 (47%) did not have any reaction.Comparing the mean wheal diameter of every EPT's dilution between the group of allergic children and the tolerant ones, we obtained a significant difference (p < 0.05) for the first 4 dilutions.We have also calculated sensitivity (SE), specificity (SP), the positive predictive value (PPV) and the negative predictive value (NPV) for each EPT dilution. CONCLUSIONS: EPT is a safe and cheap test, easy to be executed and that could provide good prediction of the outcome of OFC; so it might be used to avoid OFC-induced anaphylaxis in children affected by CMA. It can also help avoiding dietetic restrictions in tolerant children who show sensitization towards cow's milk proteins. PMID- 22053847 TI - Income replacement in retirement: longitudinal evidence from income tax records. AB - Applying an employment-income-based procedure for determining retirement, we analysed a large longitudinal data file of Canadian personal income tax returns for individuals to determine who has retired and to assess how successful they are in maintaining their incomes after retirement. The methodological approach may be of interest for possible application in other countries that have suitable data. Our main conclusions are as follows. First, in the two years immediately after retirement, the after-tax income replacement ratios average about two thirds when calculated across all ages of retirement. Second, the ratios tend to increase with the age of retirement. Third, the ratios increase with years in retirement, at least in the first few years. Finally, income replacement ratios are highest in the lowest income quartile and generally decline as income increases; within each quartile, the replacement ratios are higher for those who retired later than for those who retired earlier. PMID- 22053849 TI - Drying dip-coated colloidal films. AB - We present the results from a small-angle X-ray scattering (SAXS) study of lateral drying in thin films. The films, initially 10 MUm thick, are cast by dip coating a mica sheet in an aqueous silica dispersion (particle radius 8 nm, volume fraction phi(s) = 0.14). During evaporation, a drying front sweeps across the film. An X-ray beam is focused on a selected spot of the film, and SAXS patterns are recorded at regular time intervals. As the film evaporates, SAXS spectra measure the ordering of particles, their volume fraction, the film thickness, and the water content, and a video camera images the solid regions of the film, recognized through their scattering of light. We find that the colloidal dispersion is first concentrated to phi(s) = 0.3, where the silica particles begin to jam under the effect of their repulsive interactions. Then the particles aggregate until they form a cohesive wet solid at phi(s) = 0.68 +/- 0.02. Further evaporation from the wet solid leads to evacuation of water from pores of the film but leaves a residual water fraction phi(w) = 0.16. The whole drying process is completed within 3 min. An important finding is that, in any spot (away from boundaries), the number of particles is conserved throughout this drying process, leading to the formation of a homogeneous deposit. This implies that no flow of particles occurs in our films during drying, a behavior distinct to that encountered in the iconic coffee-stain drying. It is argued that this type of evolution is associated with the formation of a transition region that propagates ahead of the drying front. In this region the gradient of osmotic pressure balances the drag force exerted on the particles by capillary flow toward the liquid-solid front. PMID- 22053850 TI - Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer. AB - BACKGROUND: T-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy. METHODS: We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines. RESULTS: Out of several predicted epitopes, two synthetic peptides, STEAP281-296 and EZH295-109, were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP281-296 and EZH295-109 reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating in vitro T-cell responses in patients with LC. CONCLUSIONS: Peptides STEAP281-296 and EZH295-109 function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC. PMID- 22053852 TI - Helicobacter pylori cholesteryl glucosides interfere with host membrane phase and affect type IV secretion system function during infection in AGS cells. AB - Helicobacter pylori infection is an aetiological cause of gastric disorders worldwide. H. pylori has been shown to assimilate and convert host cholesterol into cholesteryl glucosides (CGs) by cholesterol-alpha-glucosyltransferase encoded by capJ. Here, we show that CapJ-deficient (DeltacapJ) H. pylori resulted in greatly reduced type IV secretion system (TFSS)-associated activities, including the hummingbird phenotype of AGS cells, IL-8 production, CagA translocation/phosphorylation and CagA-mediated signalling events. Complementation of the DeltacapJ mutation with wild type cagJ or by adding CGs containing lysates or exogenous fluorophore-tagged CGs reversed the mutant phenotypes. We also show that the wild-type but not DeltacapJ H. pylori recruited raft-associated components to sites of bacterial attachment. Fluorescence recovery after photobleaching (FRAP) analysis of AGS cells treated with fluorescence-tagged cholesterol/CGs revealed that there was a higher proportion of CGs associated with immobile fractions. CGs-associated membranes were also more resistant to a cold detergent extraction. Thus, we propose that CGs synthesized by H. pylori around host-pathogen contact sites partition in detergent-resistant membranes (DRMs), alters lateral-phase segregation in membrane and reorganizes membrane architecture. These processes together promote the formation of a functional TFSS and H. pylori infection. PMID- 22053853 TI - Functional consequences of human airway smooth muscle phenotype plasticity. AB - BACKGROUND AND PURPOSE: Airway smooth muscle (ASM) phenotype plasticity, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to increased ASM mass and airway hyper responsiveness in asthma. Further, increased expression of collagen I has been observed within the ASM bundle of asthmatics. Previously, we showed that exposure of intact bovine tracheal smooth muscle (BTSM) to collagen I induces a switch from a contractile to a hypocontractile, proliferative phenotype. However, the functional relevance of this finding for intact human ASM has not been established. EXPERIMENTAL APPROACH: We investigated the effects of exposure of human tracheal smooth muscle (HTSM) strips to monomeric collagen I and PDGF on contractile responses to methacholine and KCl. Expression of contractile proteins sm-alpha-actin and sm-MHC was assessed by Western blot analysis. The proliferation of HTSM cells was assessed by cell counting, measuring mitochondrial activity (Alamarblue conversion) and [(3) H]-thymidine incorporation. Proliferation of intact tissue slices was assessed by [(3) H] thymidine incorporation. KEY RESULTS: Culturing HTSM strips in the presence of collagen I or PDGF for 4 days reduced maximal contractile responses to methacholine or KCl and the expression of contractile proteins. Conversely, collagen I and PDGF increased proliferation of HTSM cells and proliferative responses in tissue slices. PDGF additively increased the proliferation of HTSM cells cultured on collagen I; this additive effect was not observed on contractility, contractile protein expression or proliferation of intact tissue. CONCLUSION AND IMPLICATIONS: These findings indicate that collagen I and PDGF induce a functionally hypocontractile, proliferative phenotype of human ASM, which may contribute to airway remodelling in asthma. PMID- 22053854 TI - Influence of organic acids on rheological and bread-making characteristics of fortified wheat flour. AB - Flour was fortified with premix containing ferrous fumarate and folic acid. Organic acids such as citric acid, malic acid and tartaric acid, which are promoters of iron bioavailability, were added at three levels and their influence on rheological and bread-making characteristics was studied. Farinograph water absorption increased with fortificants, but with addition of organic acids there was a decrease. Maximum pressure was 77 mm in control, which increased to 78-88 mm with the addition of different acids to the fortified flour. Addition of organic acids to fortified flour brought about a decrease in peak viscosity, hot paste viscosity, cold paste viscosity and setback values. The L, a and b values of fortified breads were similar to that of control. Sensory analysis revealed marginal differences in the overall quality of breads prepared with fortified flour with the addition of organic acids. PMID- 22053855 TI - Synthesis of bifunctional Au/Pt/Au Core/shell nanoraspberries for in situ SERS monitoring of platinum-catalyzed reactions. AB - The synthesis of bifunctional Au/Pt/Au nanoraspberries for use in quantitative in situ monitoring of platinum-catalyzed reactions by surface-enhanced Raman scattering (SERS) is presented. Highly convolved SERS spectra of reaction mixtures can be decomposed into the contributions of distinct molecular species by multivariate data analysis. PMID- 22053856 TI - Characterization of RNase MRP RNA and novel snoRNAs from Giardia intestinalis and Trichomonas vaginalis. AB - BACKGROUND: Eukaryotic cells possess a complex network of RNA machineries which function in RNA-processing and cellular regulation which includes transcription, translation, silencing, editing and epigenetic control. Studies of model organisms have shown that many ncRNAs of the RNA-infrastructure are highly conserved, but little is known from non-model protists. In this study we have conducted a genome-scale survey of medium-length ncRNAs from the protozoan parasites Giardia intestinalis and Trichomonas vaginalis. RESULTS: We have identified the previously 'missing' Giardia RNase MRP RNA, which is a key ribozyme involved in pre-rRNA processing. We have also uncovered 18 new H/ACA box snoRNAs, expanding our knowledge of the H/ACA family of snoRNAs. CONCLUSIONS: Results indicate that Giardia intestinalis and Trichomonas vaginalis, like their distant multicellular relatives, contain a rich infrastructure of RNA-based processing. From here we can investigate the evolution of RNA processing networks in eukaryotes. PMID- 22053857 TI - Effects of a dietary supplement on chronic pelvic pain syndrome (Category IIIA), leucocytospermia and semen parameters. AB - Chronic prostatitis (CP) is one of the most common male urogenital diseases and a significant public health problem in industrialised countries. It is associated with a low quality of life and significant expense. Given the poor results achieved with antibiotics, scientific interest has turned to the use of natural substances with a known activity on prostate function. The aim of our study was to evaluate the effect of a new dietary supplement containing lycopene, epigallocatechin gallate, ellagic acid, selenium and zinc on semen parameters and on leucocyte concentration in seminal fluid and expressed prostate secretion (EPS) in patients with CP without infection [National Institute of Health (NIH) Category IIIA], in comparison with a control group with the same condition who did not undergo any treatment during the study period. Our data showed a statistically significant reduction in inflammatory parameters (leucocytes in seminal fluid and EPS) and a statistically significant improvement in progressive sperm motility and sperm morphology in patients treated with the supplement in comparison with the untreated group. Improvements were also seen in the pain score of the NIH-Chronic Prostatitis Symptom Index (CPSI), confirming that the reduced inflammation also resulted in a reduction in pain. PMID- 22053858 TI - Gender, HIV status, and psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. AB - OBJECTIVE: More than 30 years after the onset of the human immunodeficiency virus (HIV) epidemic, there is no information on the prevalence of psychiatric disorders among HIV-positive individuals in the general population. We sought to compare the prevalence of 12-month psychiatric disorders among HIV-positive and HIV-negative adults stratified by sex and to examine the differential increase in risk of a psychiatric disorder as a function of the interaction of sex and HIV status. METHOD: Face-to-face interviews were conducted between 2004 and 2005 with participants in the National Epidemiologic Survey on Alcohol and Related Conditions Wave 2, a large nationally representative sample of US adults (34,653). The diagnostic interview used was the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. RESULTS: When compared with their HIV-negative same-sex counterparts, HIV-positive men were more likely to have any mood disorder (odds ratio [OR] = 6.10; 95% confidence interval [CI], 2.99-12.44), major depressive disorder/dysthymia (OR = 3.77; 95% CI, 1.16-12.27), any anxiety disorder (OR = 4.02; 95% CI, 2.12-7.64), and any personality disorder (OR = 2.50; 95% CI, 1.34-4.67). In relation to their same-sex HIV-negative counterparts, the effect of HIV status on the odds of any mood disorder (OR = 7.17; 95% CI, 2.52-20.41), any anxiety disorder (OR = 3.45; 95% CI, 1.27-9.38), and any personality disorder (OR = 2.66; 95% CI, 1.16-6.10) was significantly greater for men than women. CONCLUSIONS: HIV status was significantly more strongly associated with psychiatric disorders in men than in women. HIV-positive men had a higher prevalence than HIV-negative men of most psychiatric disorders. By contrast, HIV-positive women were not significantly more likely than HIV negative women to have psychiatric disorders. PMID- 22053860 TI - Laser irradiation of the semicircular canal: occlusion of the canal or duct. AB - The aim of this study was to evaluate the effects of argon laser irradiation of the semicircular canals using computed tomography (CT) images and to examine the basis for laser treatment for benign paroxysmal positional vertigo (BPPV). CT images of the posterior canal were evaluated postoperatively in a patient with intractable BPPV, in whom the unilateral posterior and lateral semicircular canals were irradiated with an argon laser. In addition, bootstrap analysis of 20 patients with normal CT findings of the temporal bone was performed and previous experimentally obtained histologic findings were compared. Cross-sections of the posterior canals of 20 patients were found to show no difference in size between the right and left sides. The laser-irradiated posterior canal became narrower than that on the non-irradiated healthy side in our patient. There was a discrepancy between the CT images and experimentally obtained histologic findings that showed complete occlusion of the canal. CT images of a patient with severe vertigo demonstrated that argon laser irradiation to the blue-lined semicircular canals did not occlude the canal of the corresponding areas, while the canal of the guinea pig histologically showed complete obstruction with new bone after irradiation with the same energy (1.5 W, 0.5 s, spot size: around 200 MUm in diameter). The patient has been free from vertigo for 16 years. Marked constriction of the semicircular duct corresponding to the irradiated area appeared to be effective in treating intractable BPPV. PMID- 22053859 TI - Nuclear beta-catenin overexpression in metastatic sentinel lymph node is associated with synchronous liver metastasis in colorectal cancer. AB - BACKGROUND: Beta-catenin, a component of the Wingless/Wnt signaling pathway, can activate target genes linking with the adenomatous polyposis coli (APC) gene in colorectal cancer. The purpose of this study is to investigate whether nuclear beta-catenin overexpression in metastatic sentinel lymph node(s) [SLN(s)] is associated with synchronous liver metastasis. METHODS: Clinicopathological data from 355 patients (93 cases with liver metastasis and 262 cases without liver metastasis) were reviewed. Beta-catenin expression in metastatic SLN(s) and liver metastatic lesions was examined by immunohistochemistry. The association of nuclear beta-catenin expression in metastatic SLN(s) and liver metastatic lesions was evaluated, and the relationship between nuclear beta-catenin expression and clinicopathological characteristics was analyzed. Finally, univariate and logistic multivariate regression analyses were adopted to discriminate the risk factors of liver metastasis. RESULTS: Nuclear beta-catenin overexpression in metastatic SLN(s) was observed in 70 patients with liver metastasis and 31 patients without liver metastasis (75.3% vs. 11.8%; P < 0.001). Nuclear beta catenin expression was noted in all the metastatic lesions. Spearman rank correlation analysis demonstrated that nuclear beta-catenin expression in metastatic SLN(s) had a positive correlation with that in metastatic lesions (r = 0.425, P < 0.001). Univariate and multivariate analyses indicated that nuclear beta-catenin overexpression in metastatic SLN(s) correlated with liver metastasis. CONCLUSIONS: Nuclear beta-catenin overexpression in metastatic SLN(s) is strongly associated with liver metastasis and may contribute to predict liver metastasis. PMID- 22053862 TI - Errata. PMID- 22053861 TI - Choroid plexus transport: gene deletion studies. AB - This review examines the use of transporter knockout (KO) animals to evaluate transporter function at the choroid plexus (the blood-CSF barrier; BCSFB). Compared to the blood-brain barrier, there have been few such studies on choroid plexus (CP) function. These have primarily focused on Pept2 (an oligopeptide transporter), ATP-binding cassette (ABC) transporters, Oat3 (an organic anion transporter), Svct2 (an ascorbic acid transporter), transthyretin, ion transporters, and ion and water channels. This review focuses on the knowledge gained from such studies, both with respect to specific transporters and in general to the role of the CP and its impact on brain parenchyma. It also discusses the pros and cons of using KO animals in such studies and the technical approaches that can be used. PMID- 22053865 TI - The use of complementary and alternative medicine products in preceding two days among Finnish parents - a population survey. AB - BACKGROUND: The use of complementary and alternative medicines (CAM) has been extensively studied globally among adult and paediatric populations. Parents, as a group, had not been studied to assess their knowledge and attitude to CAM and general medicine use. This study is necessary since parents' attitude to medicine use is known to influence their child's attitude to medicine use later in life. We therefore aim to assess the extent and types of CAM use among Finnish parents, and to determine the factors that promote the CAM use. Also, we aim to determine parents' attitude to general medicine use. METHODS: Children less than 12 years old, as of spring 2007, were identified from the database of the Finnish Population Register Centre and were selected by random sampling. The parents of these children were identified and a questionnaire was sent to them. Only the parent who regularly takes care of the child's medicine was requested to fill the questionnaire. Cross-tabulations and Chi-square test were used to determine the associations between categorical variables. CAMs were defined as natural products that are not registered as medicines, such as homeopathic preparations, dietary food supplements, and traditional medicinal products. RESULTS: The response rate of the survey was 67% (n = 4032). The use of CAM was 31% in the preceding two days. The most commonly used CAM products were vitamins and minerals, followed by fish oils and fatty acids. Prescription and OTC medicines were used concomitantly with CAM by one-third of the parents. CAM was frequently used by parents over 30 years (33%), female parents (32%), highly educated parents (35%), and parents with high monthly net income (3000-3999 euros, 34%). The users of CAM had more negative attitudes towards medicines than non-users of CAM. CONCLUSIONS: Our findings are in accordance with those of previous studies that women over 30 years of age with a high education and income typically use CAMs. Finnish parents seem to use CAMs as complementary rather than alternative to medicines. Health care professionals should take into consideration both the concomitant use as well as the negative attitudes among CAM users in encounters with the parents. PMID- 22053864 TI - Recommendations for mass spectrometry data quality metrics for open access data (corollary to the Amsterdam Principles). AB - Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data quality metrics. On September 18, 2010, the U.S. National Cancer Institute (NCI) convened the "International Workshop on Proteomic Data Quality Metrics" in Sydney, Australia, to identify and address issues facing the development and use of such methods for open access proteomics data. The stakeholders at the workshop enumerated the key principles underlying a framework for data quality assessment in mass spectrometry data that will meet the needs of the research community, journals, funding agencies, and data repositories. Attendees discussed and agreed up on two primary needs for the wide use of quality metrics: (1) an evolving list of comprehensive quality metrics and (2) standards accompanied by software analytics. Attendees stressed the importance of increased education and training programs to promote reliable protocols in proteomics. This workshop report explores the historic precedents, key discussions, and necessary next steps to enhance the quality of open access data. By agreement, this article is published simultaneously in the Journal of Proteome Research, Molecular and Cellular Proteomics, Proteomics, and Proteomics Clinical Applications as a public service to the research community. The peer review process was a coordinated effort conducted by a panel of referees selected by the journals. PMID- 22053866 TI - Autoimmune bone marrow environment severely inhibits B cell development by inducing extensive cell death and inhibiting proliferation. AB - The spontaneous scurfy (sf) mutation in mice results in a complete loss of Tregs, leading to a lethal, multi-system autoimmune syndrome. We have carefully examined B lymphopoiesis in sf mice. Paradoxically, the B cell numbers at all developmental stages including pro-B, pre-B, immature and mature B cells are significantly decreased in the BM and spleen of sf mice, compared to that of wild type littermate controls. The developing B cells in sf mice exhibit profoundly elevated cell death induced by down-regulation of Bcl-XL expression and up regulation of Fas expression. In addition, the clonal expansion of pre-B and immature B cells in sf mice is significantly reduced compared to wild-type controls. Foxp3 expression is not detectable in all stages of developing B cells in wild-type mice, indicating that the defects are B-cell extrinsic, which is further supported by the recovery of B cell maturation in BM chimeric mice. Remarkably, IFN-gamma production is significantly elevated in numerous cell types in the BM of sf mice. Taken together, these results indicate that the autoimmune inflammatory marrow environment has dramatic inhibitory effects on B cell development by inducing apoptosis and suppressing proliferation of developing B cells. PMID- 22053867 TI - Poly (N-isopropylacrylamide) microgel-based assemblies for organic dye removal from water. AB - Poly(N-isopropylacrylamide)-co-acrylic acid (pNIPAm-co-AAc) microgel assemblies (aggregates) were synthesized via polymerization of the cross-linker N,N' methylenebisacrylamide (BIS) in the presence of microgels in solution. In this case, the microgels were entrapped in the polymerized cross-linker network. The aggregates were investigated for their ability to remove the organic, azo dye molecule 4-(2-hydroxy-1-napthylazo) benzenesulfonic acid sodium salt (Orange II) from water at both room and elevated temperatures. These results were compared with unaggregated microgels that were previously reported (Parasuraman, D.; Serpe, M. J. ACS. Appl. Mater. Interfaces 2011, 3, 2732.). It was found that the removal efficiency increased at elevated temperature, most likely due to the thermoresponsive nature of the pNIPAm-based aggregates, which expel water of solvation and deswell at higher temperature and reswell when they are cooled back to room temperature. Furthermore, increasing the number of cycles the aggregates are heated and cooled enhanced the percent removal of the dye from water. We also evaluated the effect of increasing cross-linker concentration on the removal efficiency, where we found the removal efficiency to increase with increasing cross-linker concentration in the aggregates. The maximum removal efficiency reached by the microgel aggregates at elevated temperatures was calculated to be 73.1%. This enhanced uptake is due to the presence of larger internal volume between the microgels in the aggregates, which the individual microgels lack. Control studies reveal that the structure and hydrophobicity of the aggregates lead to the enhanced uptake efficiencies and is not due to the presence of BIS alone. We determined that aggregates leak 75.6% of the dye that was originally removed from solution. The removal of Orange II by the aggregates at room temperature was fit by a Langmuir sorption isotherm. PMID- 22053869 TI - Iodine-induced goitre and high prevalence of anaemia among Saharawi refugee women. AB - OBJECTIVE: The main objective was to assess iodine status (thyroid volume (Tvol) and urinary iodine concentration (UIC)) and their determinants in Saharawi refugee women. DESIGN: A cross-sectional survey was performed during January February 2007. Tvol was measured by ultrasound and iodine concentration was analysed in spot urine samples and in household drinking water. Anthropometry and Hb concentration were measured and background variables were collected using pre coded questionnaires. SETTING: The survey was undertaken in four long-term refugee camps in the Algerian desert. SUBJECTS: Non-pregnant women (n 394), 15-45 years old, randomly selected. RESULTS: Median (25th percentile-75th percentile (P25-P75)) UIC was 466 (294-725) MUg/l. Seventy-four per cent had UIC above 300 MUg/l and 46 % above 500 MUg/l. Median (P25-P75) Tvol was 9.4 (7.4-12.0) ml and the goitre prevalence was 22 %. UIC was positively associated with iodine in drinking water and negatively associated with breast-feeding, and these two variables explained 28 % of the variation in UIC. The mean (sd) Hb level was 11.8 (2.4) g/dl. In total 46 % were anaemic with 14 %, 25 % and 7 %, classified with respectively mild, moderate and severe anaemia. CONCLUSIONS: The Saharawi women had high UIC, high levels of iodine in drinking water and increased Tvol and probably suffered from iodine-induced goitre. The high prevalence of anaemia is considered to be a severe public health concern. To what extent the excessive iodine intake and the anaemia have affected thyroid function is unknown and should be addressed in future studies. PMID- 22053870 TI - Stimuli-responsive hydrogel hollow capsules by material efficient and robust cross-linking-precipitation synthesis revisited. AB - Monodisperse stimuli-responsive hydrogel capsules were synthesized in the 100-nm diameter to 10-MUm-diameter range from poly(4-vinylpyridine) (P4VP) and poly(ethyleneimine) (PEI) through a simple, efficient two-step cross-linking precipitation template method under conditions of a good solvent. In this method, the core-shell particles were obtained by the deposition (heterocoagulation mechanism) of the cross-linked P4VP, PEI, or their mixtures on the surfaces of the template colloidal silica particles in nitromethane (for PEI) or a nitromethane-acetone mixture (for P4VP and P4VP-PEI mixtures) in the presence of cross-linker 1,4-diiodobutane. The cross-linked polymeric shell swollen in a good solvent stabilized the core-shell colloids. This mechanism provided the conditions for the synthesis of core-shell colloids in a submicrometer range of dimensions with an easily adjusted shell thickness (wall of the capsules) ranging from a few to hundreds of nanometers. The chemical composition of the shell was tuned by varying the ratio of co-cross-linked shell-forming polymers (P4VP and PEI). In the second step, the hollow capsules were obtained by etching the silica core in HF solutions. In this step, the colloidal stability of the hollow capsules was provided by ionized P4VP and PEI cross-linked shells. The hollow capsules demonstrate that the pH- and ionic-strength-triggered swelling and shrinking result in size-selective uptake and release properties. Cross-linked via quaternized functional groups, P4VP capsules undergo swelling and shrinking transitions at a physiologically relevant pH of around 6. The 200-nm-diameter hollow capsule with 25-nm-thick walls demonstrated a factor of 2 greater capacity to accommodate cargo molecules than the core-shell particles of the same dimensions because of an internal compartment and a combination of radial and a circumferential swelling modes in the capsules. PMID- 22053872 TI - Self-adjusted sustaining oscillation of confined water chain in carbon nanotubes. AB - We show by molecular dynamics and first principle calculations that a water chain confined in carbon nanotubes can self-adjust into regular oscillation with remarkably lower entropy from random thermal motion with higher entropy at room temperature. The turning between the two phases is triggered by the water orientation fluttering into or from the energy optimum configuration of the chain. The findings are expected to be helpful in creation of self-sustaining nanoelectromechanical systems driven by ambient energy. PMID- 22053873 TI - An examination of instrumental activities of daily living assessment in older adults and mild cognitive impairment. AB - Basic activities of daily living (ADL) are self-maintenance abilities such as dressing or bathing. Instrumental ADL (IADL) are more complex everyday tasks, such as preparing a meal or managing finances (Lawton & Brody, 1969). IADL questionnaires play an important role in assessing the functional abilities of older adults and evaluating the impact of cognitive impairment on routine activities. This paper examined the cognitive processes that underlie IADL performance and concluded that the accurate and reliable execution of IADL likely draws upon the integrity of a wide range of cognitive processes. This review examined IADL in mild cognitive impairment (MCI) because of the controversial nature of distinguishing a significant decline in functional abilities in those with MCI versus dementia or MCI versus cognitively normal aging. The challenges of investigating IADL empirically were explored, as well as some of the reasons for the inconsistent findings in the literature. A review of questionnaire-based assessments of IADL indicated that: MCI can be distinguished statistically from healthy older adults and dementia, individuals with multiple domain MCI are more impaired on IADL than those with single domain MCI, mild IADL changes can be predictive of future cognitive decline, and the ability to manage finances may be among the earliest IADL changes in MCI and a strong predictor of conversion to dementia. This paper concluded with recommendations for more sensitive and reliable IADL questionnaires. PMID- 22053874 TI - Two small RNAs, CrcY and CrcZ, act in concert to sequester the Crc global regulator in Pseudomonas putida, modulating catabolite repression. AB - The Crc protein is a translational repressor that recognizes a specific target at some mRNAs, controlling catabolite repression and co-ordinating carbon metabolism in pseudomonads. In Pseudomonas aeruginosa, the levels of free Crc protein are controlled by CrcZ, a sRNA that sequesters Crc, acting as an antagonist. We show that, in Pseudomonas putida, the levels of free Crc are controlled by CrcZ and by a novel 368 nt sRNA named CrcY. CrcZ and CrcY, which contain six potential targets for Crc, were able to bind Crc specifically in vitro. The levels of CrcZ and CrcY were low under conditions generating a strong catabolite repression, and increased strongly when catabolite repression was absent. Deletion of either crcZ or crcY had no effect on catabolite repression, but the simultaneous absence of both sRNAs led to constitutive catabolite repression that compromised growth on some carbon sources. Overproduction of CrcZ or CrcY significantly reduced repression. We propose that CrcZ and CrcY act in concert, sequestering and modulating the levels of free Crc according to metabolic conditions. The CbrA/CbrB two-component system activated crcZ transcription, but had little effect on crcY. CrcY was detected in P. putida, Pseudomonas fluorescens and Pseudomonas syringae, but not in P. aeruginosa. PMID- 22053875 TI - HopAS1 recognition significantly contributes to Arabidopsis nonhost resistance to Pseudomonas syringae pathogens. AB - * Plant immunity is activated by sensing either conserved microbial signatures, called pathogen/microbe-associated molecular patterns (P/MAMPs), or specific effectors secreted by pathogens. However, it is not known why most microbes are nonpathogenic in most plant species. * Nonhost resistance (NHR) consists of multiple layers of innate immunity and protects plants from the vast majority of potentially pathogenic microbes. Effector-triggered immunity (ETI) has been implicated in race-specific disease resistance. However, the role of ETI in NHR is unclear. * Pseudomonas syringae pv. tomato (Pto) T1 is pathogenic in tomato (Solanum lycopersicum) yet nonpathogenic in Arabidopsis. Here, we show that, in addition to the type III secretion system (T3SS)-dependent effector (T3SE) avrRpt2, a second T3SE of Pto T1, hopAS1, triggers ETI in nonhost Arabidopsis. * hopAS1 is broadly present in P. syringae strains, contributes to virulence in tomato, and is quantitatively required for Arabidopsis NHR to Pto T1. Strikingly, all tested P. syringae strains that are pathogenic in Arabidopsis carry truncated hopAS1 variants of forms, demonstrating that HopAS1-triggered immunity plays an important role in Arabidopsis NHR to a broad-range of P. syringae strains. PMID- 22053876 TI - Evaluating interaction forces between BSA and rabbit anti-BSA in sulphathiazole sodium, tylosin and levofloxacin solution by AFM. AB - Protein-protein interactions play crucial roles in numerous biological processes. However, it is still challenging to evaluate the protein-protein interactions, such as antigen and antibody, in the presence of drug molecules in physiological liquid. In this study, the interaction between bovine serum albumin (BSA) and rabbit anti-BSA was investigated using atomic force microscopy (AFM) in the presence of various antimicrobial drugs (sulphathiazole sodium, tylosin and levofloxacin) under physiological condition. The results show that increasing the concentration of tylosin decreased the single-molecule-specific force between BSA and rabbit anti-BSA. As for sulphathiazole sodium, it dramatically decreased the specific force at a certain critical concentration, but increased the nonspecific force as its concentration increasing. In addition, the presence of levofloxacin did not greatly influence either the specific or nonspecific force. Collectively, these results suggest that these three drugs may adopt different mechanisms to affect the interaction force between BSA and rabbit anti-BSA. These findings may enhance our understanding of antigen/antibody binding processes in the presence of drug molecules, and hence indicate that AFM could be helpful in the design and screening of drugs-modulating protein-protein interaction processes. PMID- 22053877 TI - Venom immunotherapy: pitfalls and open questions. PMID- 22053878 TI - Low-dose IL-2 as a therapeutic agent for tolerance induction. PMID- 22053880 TI - Is A20 a suitable target to enhance dendritic cell antigen presentation? PMID- 22053881 TI - The first biological approved to treat systemic lupus erythematosus. PMID- 22053883 TI - Otelixizumab in the treatment of type 1 diabetes mellitus. AB - Anti-CD3 antibodies have been demonstrated in both animal and human studies to be able to reverse autoimmune diseases; for example Type 1 diabetes. Not only does treatment with anti-CD3 antibodies result in the removal of pathogenic T cells but evidence suggests that a state of operational tolerance can be induced through the effects on regulatory T cells. The clinical use of anti-CD3 antibodies has been hampered by their safety profile. However, the introduction of humanized, nonmitogenic, aglycosylated anti-CD3 antibodies, such as otelixizumab, and promising results reported in newly-diagnosed patients with Type 1 diabetes, have renewed the interest for these antibodies in the treatment of autoimmune diseases. PMID- 22053885 TI - Cytokine blockade in inflammatory bowel diseases. AB - Inflammatory bowel diseases (IBDs) are chronic disabling diseases with significant morbidity. A deregulated immune response towards the intestinal microbiota is thought to play an important role in the pathogenesis of IBD, and thus biological therapies targeting key molecules such as cytokines have been designed. Several anti-TNF-alpha agents are currently being used to treat Crohn's disease and ulcerative colitis. Although these molecules dramatically improved the treatment of patients, side effects and the development of antidrug antibodies limits their application. There is thus an urgent need for alternative approaches to decrease inflammation and limit immunogenicity. Small neutralizing molecules, active immunization, gene silencing, selective transcription inhibitors and delivery of agents through the oral route are some of the currently developed strategies to meet these needs. In parallel, neutralizing antibodies targeting other pathways of the immune system have been developed and tested. Antibodies targeting IL-12/IL-23 pathways, and proinflammatory cytokines such as IFN-gamma, IL-17A, IL-2 and IL-6 often showed an initial promising result, but for none of these agents efficacy has unequivocally been established. Administration of the regulatory cytokines IL-10 and IL-11 also failed to induce reproducible clinical effects. This article focuses on the anti-TNF therapies and the current challenges with monoclonal antibody therapies, discusses the innovative strategies targeting cytokine pathways to decrease inflammation in the bowel, and summarizes the recently developed agents neutralizing proinflammatory cytokines. PMID- 22053884 TI - Chemokines, costimulatory molecules and fusion proteins for the immunotherapy of solid tumors. AB - In this article, the role of chemokines and costimulatory molecules in the immunotherapy of experimental murine solid tumors and immunotherapy used in ongoing clinical trials are presented. Chemokine networks regulate physiologic cell migration that may be disrupted to inhibit antitumor immune responses or co opted to promote tumor growth and metastasis in cancer. Recent studies highlight the potential use of chemokines in cancer immunotherapy to improve innate and adaptive cell interactions and to recruit immune effector cells into the tumor microenvironment. Another critical component of antitumor immune responses is antigen priming and activation of effector cells. Reciprocal expression and binding of costimulatory molecules and their ligands by antigen-presenting cells and naive lymphocytes ensures robust expansion, activity and survival of tumor specific effector cells in vivo. Immunotherapy approaches using agonist antibodies or fusion proteins of immunomodulatory molecules significantly inhibit tumor growth and boost cell-mediated immunity. To localize immune stimulation to the tumor site, a series of fusion proteins consisting of a tumor-targeting monoclonal antibody directed against tumor necrosis and chemokines or costimulatory molecules were generated and tested in tumor-bearing mice. While several of these reagents were initially shown to have therapeutic value, combination therapies with methods to delete suppressor cells had the greatest effect on tumor growth. In conclusion, a key conclusion that has emerged from these studies is that successful immunotherapy will require both advanced methods of immunostimulation and the removal of immunosuppression in the host. PMID- 22053886 TI - Notch and inflammatory T-cell response: new developments and challenges. AB - The inflammatory T-cell response is important for protecting the host against infections and tumors. However, dysregulated generation of effector T cells produces high levels of inflammatory cytokines and cytotoxic molecules and may cause inflammatory disorders, such as chronic infections, autoimmune diseases and graft-versus-host disease after allogeneic bone marrow transplantation. Thus, tight regulation of effector T cells is essential. Accumulating evidence indicates that Notch plays critical roles in regulating the differentiation of antigen activated T cells into distinct lineages of effector T cells. Furthermore, significant progress has been made in the development of new methods in order to modulate Notch for disease treatment. In this article, we will discuss recent findings that help to gain insight into the impact of Notch in the regulation of effector T cells and highlight the beneficial effects of modulating Notch in inflammatory diseases. PMID- 22053887 TI - The tumor microenvironment: part 1. AB - For years the mutated, highly proliferating neoplastic cells were presented as the only important agent in tumors; however, during the last 3-4 decades it has become clear that the microenvironment of the cancer cells plays a determinative role in the malignant evolution of neoplasia. Cancers are in fact heterogeneous entities containing, in addition to the neoplastic cell component, cells derived of multiple lineages (fibroblasts, endothelial cells lining blood and lymphatic vessels, pericytes, adipocytes and immune system cells belonging to both innate and adaptive responses), as well as the extracellular matrix, with a large variety of soluble molecules of biological importance, constituting a complex organ-like structure. The tumor microenvironment consists in a tissue that may have a predictive significance for tumor behavior and response to therapy. PMID- 22053888 TI - Targeting the tumor microenvironment by immunotherapy: part 2. AB - Cancer therapy was traditionally centered on the neoplastic cells. This included mainly surgery, radiation, and chemotherapy, in some cases hormone therapy and to a lesser extent immunotherapy--all traditionally targeted to the highly proliferating mutated tumor cells. In view of our present understanding of the powerfull influence of the tumor microenvironment (TME) on cancer behavior and response--and lack of response--to treatment, this previously ignored constituent of cancer now has to be considered as an important, even indispensable target for therapy. The TME may be targeted both to its immune and to its nonimmune components. The various immune evasion elements of the TME should be targeted as well. PMID- 22053890 TI - Erratum. PMID- 22053891 TI - Postcardiac arrest syndrome: from immediate resuscitation to long-term outcome. AB - The prognosis for postcardiac arrest patients remains very bleak, not only because of anoxic-ischemic neurological damage, but also because of the "postcardiac arrest syndrome," a phenomenon often severe enough to cause death before any neurological evaluation. This syndrome includes all clinical and biological manifestations related to the phenomenon of global ischemia reperfusion triggered by cardiac arrest and return of spontaneous circulation. The main component of the postcardiac arrest syndrome is an early but severe cardiocirculatory dysfunction that may lead to multiple organ failure and death.Cardiovascular support relies on conventional medical and mechanical treatment of circulatory failure. Hemodynamic stabilization is a major objective to limit secondary brain insult. When the cause of cardiac arrest is related to myocardial infarction, percutaneous coronary revascularization is associated with improved prognosis; early angiographic exploration should then be discussed when there is no obvious extracardiac cause. Therapeutic hypothermia is now the cornerstone of postanoxic cerebral protection. Its widespread use is clearly recommended, with a favorable risk-benefit ratio in selected population. Neuroprotection also is based on the prevention of secondary cerebral damages, pending the results of ongoing therapeutic evaluations regarding the potential efficiency of new therapeutic drugs. PMID- 22053892 TI - Unmasking the janus faces of autophagy in obesity-associated insulin resistance and cardiac dysfunction. AB - Autophagy is an intracellular, lysosomal-dependent process involved in the turnover of long-lived proteins, damaged organelles and other subcellular structures. The autophagic process is known to play an essential role in the maintenance of cellular homeostasis. Results from recent studies also indicate an important role for the autophagic process in the pathogenesis of human diseases, including cancer, cardiovascular diseases, obesity, diabetes mellitus and ageing. Because of the pivotal role of autophagy in the regulation of adipogenesis, obesity and insulin sensitization, research efforts have focused on elucidating the role of autophagy in metabolic syndrome. Mammalian target of rapamycin (mTOR) is a key regulator of cell growth and is characterized by a complex signalling mechanism that affects protein synthesis and autophagy. Results from experimental and clinical studies reveal some interesting, but conflicting, findings regarding the mTOR signalling pathway and autophagy in adipocytes in metabolic syndrome. Although the pivotal role of autophagy in obesity and other metabolic diseases has been established, its involvement in obesity-induced cardiac dysfunction remains unknown, as do the upstream signalling regulators of autophagy. The present minireview discusses the molecular mechanisms of autophagy in the regulation of cardiac function in overweight and obesity. Further studies using appropriate models are needed to better unravel the complex intracellular mechanisms involved in the regulation of autophagy in obesity-induced cardiac dysfunction. PMID- 22053893 TI - Loop-mediated isothermal amplification (LAMP) assays for the species-specific detection of Eimeria that infect chickens. AB - BACKGROUND: Eimeria parasites can cause the disease coccidiosis in poultry and even subclinical infection can incur economic loss. Diagnosis of infection predominantly relies on traditional techniques including lesion scoring and faecal microscopy despite the availability of sensitive molecular assays, largely due to cost and the requirement for specialist equipment. Despite longstanding proven efficacy these traditional techniques demand time and expertise, can be highly subjective and may under-diagnose subclinical disease. Recognition of the tight economic margins prevailing in modern poultry production and the impact of avian coccidiosis on poverty in many parts of the world has highlighted a requirement for a panel of straightforward and sensitive, but cost-effective, Eimeria species-specific diagnostic assays. RESULTS: Loop-mediated isothermal amplification (LAMP) is an uncomplicated, quick and relatively inexpensive diagnostic tool. In this study we have developed a panel of species-specific LAMP assays targeting the seven Eimeria species that infect the chicken. Each assay has been shown to be genuinely species-specific with the capacity to detect between one and ten eimerian genomes, equivalent to less than a single mature schizont. Development of a simple protocol for template DNA preparation from tissue collected post mortem with no requirement for specialist laboratory equipment supports the use of these assays in routine diagnosis of eimerian infection. Preliminary field testing supports this hypothesis. CONCLUSIONS: Development of a panel of sensitive species-specific LAMP assays introduces a valuable new cost-effective tool for use in poultry husbandry. PMID- 22053896 TI - F-Doped Co3O4 photocatalysts for sustainable H2 generation from water/ethanol. AB - p-Type Co(3)O(4) nanostructured films are synthesized by a plasma-assisted process and tested in the photocatalytic production of H(2) from water/ethanol solutions under both near-UV and solar irradiation. It is demonstrated that the introduction of fluorine into p-type Co(3)O(4) results in a remarkable performance improvement with respect to the corresponding undoped oxide, highlighting F-doped Co(3)O(4) films as highly promising systems for hydrogen generation. Notably, the obtained yields were among the best ever reported for similar semiconductor-based photocatalytic processes. PMID- 22053894 TI - Oral Candida albicans isolates from HIV-positive individuals have similar in vitro biofilm-forming ability and pathogenicity as invasive Candida isolates. AB - BACKGROUND: Candida can cause mucocutaneous and/or systemic infections in hospitalized and immunosuppressed patients. Most individuals are colonized by Candida spp. as part of the oral flora and the intestinal tract. We compared oral and systemic isolates for the capacity to form biofilm in an in vitro biofilm model and pathogenicity in the Galleria mellonella infection model. The oral Candida strains were isolated from the HIV patients and included species of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. norvegensis, and C. dubliniensis. The systemic strains were isolated from patients with invasive candidiasis and included species of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. lusitaniae, and C. kefyr. For each of the acquired strains, biofilm formation was evaluated on standardized samples of silicone pads and acrylic resin. We assessed the pathogenicity of the strains by infecting G. mellonella animals with Candida strains and observing survival. RESULTS: The biofilm formation and pathogenicity in Galleria was similar between oral and systemic isolates. The quantity of biofilm formed and the virulence in G. mellonella were different for each of the species studied. On silicone pads, C. albicans and C. dubliniensis produced more biofilm (1.12 to 6.61 mg) than the other species (0.25 to 3.66 mg). However, all Candida species produced a similar biofilm on acrylic resin, material used in dental prostheses. C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis were the most virulent species in G. mellonella with 100% of mortality, followed by C. lusitaniae (87%), C. novergensis (37%), C. krusei (25%), C. glabrata (20%), and C. kefyr (12%). CONCLUSIONS: We found that on silicone pads as well as in the Galleria model, biofilm formation and virulence depends on the Candida species. Importantly, for C. albicans the pathogenicity of oral Candida isolates was similar to systemic Candida isolates, suggesting that Candida isolates have similar biofilm-forming ability and virulence regardless of the infection site from which it was isolated. PMID- 22053897 TI - Early response and remission as predictors of a good outcome of a major depressive episode at 12-month follow-up: a prospective, longitudinal, observational study. AB - OBJECTIVE: The goal of treating major depressive disorder (MDD) should be not only achieving remission in a particular episode but also avoiding relapses and attaining long-term recovery. The current study was designed to evaluate whether response and remission achieved within the first 6 weeks of antidepressant treatment are associated with a 12-month good outcome (achieving remission by 6 months and remaining in remission until the end of follow-up). METHOD: This prospective, longitudinal, multicenter study included adult outpatients who had a DSM-IV diagnosis of MDD, baseline scores >= 15 on the 17-item Hamilton Depression Rating Scale (HDRS(17)), Clinical Global Impressions-Severity of Illness scores >= 4, and a minimum remission period of 12 weeks between the index episode and the immediately prior episode (or who were in their first MDD episode). The primary efficacy measure was early response (a 50% decrease from baseline in HDRS(17) score by week 6). The secondary efficacy measure was early remission (HDRS(17) score <= 7 by week 6). RESULTS: Among the total of 930 patients included from December 2006 to June 2007, 38.2% showed early response, and 20.5% showed early remission. Of the early responders, 76.1% had a 12-month good outcome as compared to 81.1% of early remitters. Logistic regression showed that factors associated with a good outcome included early response (odds ratio [OR] = 4.14), being employed, and the absence of physical comorbidities. Early remission was also strongly associated with a good outcome (OR = 4.72). CONCLUSIONS: Either response or remission achieved by week 6 is the strongest prognostic factor for the 12-month good outcome of an episode of MDD. PMID- 22053898 TI - IFIH1 gene polymorphisms in type 1 diabetes: genetic association analysis and genotype-phenotype correlation in Chinese Han population. AB - The evaluation of susceptibility loci is an important addition to the current predictive and screening models in type 1 diabetes of Chinese Han population. Therefore, the aim of this study is to provide evidence for the association between type 1 diabetes and two polymorphisms (rs3747517, rs1990760) from interferon induced with helicase C domain 1 (IFIH1). Here, 464 Type 1 diabetes patients and 465 control subjects were genotyped for these 2 polymorphisms. The results indicated that the allelic frequencies of rs3747517 revealed a strong association with type 1 diabetes risk (P < 0.001); yet, no significant association was observed on rs1990760(P = 0.76). Furthermore, IFIH1 rs3747517 polymorphism had no influence on the positive rates of pancreatic auto antibodies, and both of the polymorphisms had no interaction with HLA class I linked risk or phenotypes. In conclusion, IFIH1 rs3747517, but not rs1990760 polymorphism, plays an important role in type 1 diabetes risk in Chinese Han population. PMID- 22053899 TI - Comparison of pretargeted and conventional CC49 radioimmunotherapy using 149Pm, 166Ho, and 177Lu. AB - The therapeutic efficacies of radiolabeled biotin, pretargeted by monoclonal antibody (mAb)-streptavidin fusion protein CC49 scFvSA, were compared to those of radiolabeled mAb CC49, using the three radiolanthanides in an animal model of human colon cancer. The purpose of the present study was to compare antibody pretargeting to conventional radioimmunotherapy using (149)Pm, (166)Ho, or (177)Lu. Nude mice bearing LS174T colon tumors were injected sequentially with CC49 scFvSA, the blood clearing agent biotin-GalNAc(16), and (149)Pm-, (166)Ho-, or (177)Lu-DOTA-biotin. Tumor-bearing mice were alternatively administered (149)Pm-, (166)Ho-, or (177)Lu-MeO-DOTA-CC49. Therapy with pretargeted (149)Pm ,(166)Ho-, and (177)Lu-DOTA-biotin increased the median time of progression to a 1 g tumor to 50, 41, and 50 days post-treatment, respectively. Therapy with (149)Pm-,(166)Ho-, and (177)Lu-MeO-DOTA-CC49 increased the median time to progression to 53, 24, and 67 days post-treatment, respectively. In contrast, saline controls showed a median time to progression of 13 days postinjection. Treatment with pretargeted (149)Pm-, (166)Ho-, and (177)Lu-biotin or (149)Pm-, (166)Ho-, and (177)Lu-CC49 increased tumor doubling time to 18-36 days, compared to 3 days for saline controls. Among treated mice, 23% survived >84 days post therapy, and 11% survived 6 months, but controls survived <29 days. Long-term survivors showed tumor growth inhibition or partial regression, extensive necrosis in residual masses, and no evidence of nontarget tissue toxicity at necropsy. Both pretargeted and conventional RIT demonstrated considerable efficacy in an extremely aggressive animal model of cancer. Our results identified (177)Lu as an optimal radiolanthanide for future evaluation of these agents in toxicity and multiple-dose therapy studies. PMID- 22053901 TI - Correlation between caloric and ocular vestibular evoked myogenic potential test results. AB - CONCLUSION: The ocular vestibular evoked myogenic potential (o-VEMP) test results correlate significantly with caloric test results for patients with acoustic neuroma (AN), but not for patients with Meniere's disease (MD), indicating that the o-VEMP test may replace the caloric test for evaluating the vestibular nerve from which the AN arises. Conversely, the caloric, o-VEMP, and cervical VEMP (c VEMP) tests should be performed to map lesion sites in the vestibular labyrinth. OBJECTIVE: This study performed caloric, o-VEMP, and c-VEMP tests on patients with central and peripheral vestibular disorders to investigate their relationships. METHODS: In all, 66 patients comprising 16 with unilateral AN and 50 with unilateral definite MD were enrolled. All patients underwent caloric, o VEMP, and c-VEMP tests. RESULTS: In the AN group, the caloric test identified canal paresis and caloric areflexia in 10 ears, while the o-VEMP and c-VEMP tests identified abnormal (absent or delayed) responses in 12 and 11 ears, respectively. A significant correlation existed between caloric and o-VEMP test results, but not between caloric and c-VEMP test results, or between o-VEMP and c VEMP test results. For the MD group, abnormal caloric, o-VEMP, and c-VEMP test results were obtained for 24%, 44%, and 38% of hydropic ears, respectively. No correlation existed between any two test results. PMID- 22053900 TI - Antimicrobial activity against oral pathogens and immunomodulatory effects and toxicity of geopropolis produced by the stingless bee Melipona fasciculata Smith. AB - BACKGROUND: Native bees of the tribe Meliponini produce a distinct kind of propolis called geopropolis. Although many pharmacological activities of propolis have already been demonstrated, little is known about geopropolis, particularly regarding its antimicrobial activity against oral pathogens. The present study aimed at investigating the antimicrobial activity of M. fasciculata geopropolis against oral pathogens, its effects on S. mutans biofilms, and the chemical contents of the extracts. A gel prepared with a geopropolis extract was also analyzed for its activity on S. mutans and its immunotoxicological potential. METHODS: Antimicrobial activities of three hydroalcoholic extracts (HAEs) of geopropolis, and hexane and chloroform fractions of one extract, were evaluated using the agar diffusion method and the broth dilution technique. Ethanol (70%, v/v) and chlorhexidine (0.12%, w/w) were used as negative and positive controls, respectively. Total phenol and flavonoid concentrations were assayed by spectrophotometry. Immunotoxicity was evaluated in mice by topical application in the oral cavity followed by quantification of biochemical and immunological parameters, and macro-microscopic analysis of animal organs. RESULTS: Two extracts, HAE-2 and HAE-3, showed inhibition zones ranging from 9 to 13 mm in diameter for S. mutans and C. albicans, but presented no activity against L. acidophilus. The MBCs for HAE-2 and HAE-3 against S. mutans were 6.25 mg/mL and 12.5 mg/mL, respectively. HAE-2 was fractionated, and its chloroform fraction had an MBC of 14.57 mg/mL. HAE-2 also exhibited bactericidal effects on S. mutans biofilms after 3 h of treatment. Significant differences (p < 0.05) in total phenol and flavonoid concentrations were observed among the samples. Signs toxic effects were not observed after application of the geopropolis-based gel, but an increase in the production of IL-4 and IL-10, anti-inflammatory cytokines, was detected. CONCLUSIONS: In summary, geopropolis produced by M. fasciculata can exert antimicrobial action against S. mutans and C. albicans, with significant inhibitory activity against S. mutans biofilms. The extract with the highest flavonoid concentration, HAE-2, presented the highest antimicrobial activity. In addition, a geopropolis-based gel is not toxic in an animal model and displays anti-inflammatory effect. PMID- 22053902 TI - Brush-shaped ZnO heteronanorods synthesized using thermal-assisted pulsed laser deposition. AB - Brush-shaped ZnO heteronanostructures were synthesized using a newly designed thermal-assisted pulsed laser deposition (T-PLD) system that combines the advantages of pulsed laser deposition (PLD) and a hot furnace system. Branched ZnO nanostructures were successfully grown onto CVD-grown backbone nanowires by T PLD. Although ZnO growth at 300 degrees C resulted in core-shell structures, brush-shaped hierarchical nanostructures were formed at 500-600 degrees C. Materials properties were studied via photoluminescence (PL), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterizations. The enhanced photocurrent of a SnO(2)-ZnO heterostructures device by irradiation with 365 nm wavelength ultraviolet (UV) light was also investigated by the current-voltage characteristics. PMID- 22053903 TI - Material properties of matrix lipids determine the conformation and intermolecular reactivity of diacetylenic phosphatidylcholine in the lipid bilayer. AB - Photopolymerizable phospholipid DC(8,9)PC (1,2-bis-(tricosa-10,12-diynoyl)-sn glycero-3-phosphocholine) exhibits unique assembly characteristics in the lipid bilayer. Because of the presence of the diacetylene groups, DC(8,9)PC undergoes polymerization upon UV (254 nm) exposure and assumes chromogenic properties. DC(8,9)PC photopolymerization in gel-phase matrix lipid 1,2-dipalmitoyl-sn glycero-3-phosphocholine (DPPC) monitored by UV-vis absorption spectroscopy occurred within 2 min after UV treatment, whereas no spectral shifts were observed when DC(8,9)PC was incorporated into liquid-phase matrix 1-palmitoyl-2 oleoyl-sn-glycero-3-phosphocholine (POPC). Liquid chromatography-tandem mass spectrometry analysis showed a decrease in the amount of DC(8,9)PC monomer in both DPPC and POPC environments without any change in the matrix lipids in UV treated samples. Molecular dynamics (MD) simulations of DPPC/DC(8,9)PC and POPC/DC(8,9)PC bilayers indicate that the DC(8,9)PC molecules adjust to the thickness of the matrix lipid bilayer. Furthermore, the motions of DC(8,9)PC in the gel-phase bilayer are more restricted than in the fluid bilayer. The restricted motional flexibility of DC(8,9)PC (in the gel phase) enables the reactive diacetylenes in individual molecules to align and undergo polymerization, whereas the unrestricted motions in the fluid bilayer restrict polymerization because of the lack of appropriate alignment of the DC(8,9)PC fatty acyl chains. Fluorescence microscopy data indicates the homogeneous distribution of lipid probe 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N lissamine rhodamine B sulfonyl ammonium salt (N-Rh-PE) in POPC/DC(8,9)PC monolayers but domain formation in DPPC/DC(8,9)PC monolayers. These results show that the DC(8,9)PC molecules cluster and assume the preferred conformation in the gel-phase matrix for the UV-triggered polymerization reaction. PMID- 22053904 TI - Microvascular injury in very late mixed rejection: a not so easy marker to be identified. PMID- 22053905 TI - Catalytic, asymmetric, interrupted Feist-Benary reactions of alpha tosyloxyacetophenones. AB - A new variant of the Interrupted Feist-Benary (IFB) reaction uses alpha tosyloxyacetophenones as electrophiles and proceeds in good yields and excellent enantioselectivities. PMID- 22053907 TI - Gold colloidal nanoparticle electrodeposition on a silicon surface in a uniform electric field. AB - The electrodeposition of gold colloidal nanoparticles on a silicon wafer in a uniform electric field is investigated using scanning electron microscopy and homemade electrochemical cells. Dense and uniform distributions of particles are obtained with no aggregation. The evolution of surface particle density is analyzed in relation to several parameters: applied voltage, electric field, exchanged charge. Electrical, chemical, and electrohydrodynamical parameters are taken into account in describing the electromigration process. PMID- 22053906 TI - Gut microbiota modulate the metabolism of brown adipose tissue in mice. AB - A two by two experimental study has been designed to determine the effect of gut microbiota on energy metabolism in mouse models. The metabolic phenotype of germ free (GF, n = 20) and conventional (n = 20) mice was characterized using a NMR spectroscopy-based metabolic profiling approach, with a focus on sexual dimorphism (20 males, 20 females) and energy metabolism in urine, plasma, liver, and brown adipose tissue (BAT). Physiological data of age-matched GF and conventional mice showed that male animals had a higher weight than females in both groups. In addition, conventional males had a significantly higher total body fat content (TBFC) compared to conventional females, whereas this sexual dimorphism disappeared in GF animals (i.e., male GF mice had a TBFC similar to those of conventional and GF females). Profiling of BAT hydrophilic extracts revealed that sexual dimorphism in normal mice was absent in GF animals, which also displayed lower BAT lactate levels and higher levels of (D)-3 hydroxybutyrate in liver, plasma, and BAT, together with lower circulating levels of VLDL. These data indicate that the gut microbiota modulate the lipid metabolism in BAT, as the absence of gut microbiota stimulated both hepatic and BAT lipolysis while inhibiting lipogenesis. We also demonstrated that (1)H NMR metabolic profiles of BAT were excellent predictors of BW and TBFC, indicating the potential of BAT to fight against obesity. PMID- 22053909 TI - Fuzzy rule based classification and quantification of graphite inclusions from microstructure images of cast iron. AB - The quantification of three classes of graphite inclusions in cast iron, namely, nodular, flake, and irregular, is the most important process in the foundry industry. This classification is based on the ISO 945 proposed morphology of graphite inclusions. This work presents a novel solution for automatic quantitative analysis of graphite inclusions into the three mentioned classes. The proposed work comprises three stages, namely, preprocessing of micrographs, classification of graphite inclusions, and then quantification of inclusions in each class. An effort has been made in this work to propose a minimum set of features to represent graphite inclusion morphology. The method employs just two geometric shape descriptors: the diameter ratio and the area ratio. A fuzzy rule based classifier is built using known feature values that are efficient in the classification of the three classes of graphite inclusions. The proposed method is automatic, fast, and provides the basis for determining many more morphological parameters that can be determined with the least effort. The results obtained by the proposed method are compared with the manual method. It is observed that the results obtained from the proposed method are useful in the optimization of cast iron manufacturing in the foundry industry. PMID- 22053910 TI - Photochemical inactivation of Pseudomonas aeruginosa. AB - Adaptability to a broad range of environments together with relatively high resistance to antibiotics and to disinfectants makes Pseudomonas aeruginosa a concern in hospitals and in public health. We investigated whether UVA-mediated photochemical inactivation of P. aeruginosa could be accomplished with high efficiency while at the same time preserving the sensitivity of subsequent diagnostic tests. We characterized dose responses and bactericidal kinetic rates of 5-iodonaphthyl 1-azide (INA) and of amotosalen (AMO) as these substances exposed to UVA are known to inactivate germs with minimal impact to blood products or to viral antigens. Neither UVA without photochemicals nor INA or AMO in the dark inactivated bacteria. We found that AMO was ca 1000-fold more effective in inactivating P. aeruginosa cells than INA under similar conditions. Photoinactivation with either INA or AMO at conditions that abolished bacterial infectivity did not impair polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) testing. For comparison, similar titers of Bacillus atrophaeus spores (a surrogate for B. anthracis) remained unaffected at conditions that reduced the survival of P. aeruginosa below detection levels. The results presented in this study should assist in improved methods to inactivate P. aeruginosa in environmental, clinical and forensic samples without impairing subsequent nucleic acid- or immune-based analysis. PMID- 22053911 TI - Identification of three oligo-/polysaccharide-specific ligases in Yersinia enterocolitica. AB - In lipopolysaccharide (LPS) biosynthesis of gram-negative bacteria the lipid A core oligosaccharide (LA-core) and O-polysaccharide (O-PS) biosynthesis pathways proceed separately and converge in periplasmic space where the waaL-encoded ligase joins O-PS onto LA-core. Enterobacterial common antigen (ECA) biosynthesis follows that of O-PS except that ECA is usually ligated to phosphatidylglycerol (PG) and only rarely to LA-core. In Yersinia enterocolitica serotype O:3 LPS is composed of LA-inner core (IC) onto which a homopolymeric O-PS, a hexasaccharide called outer core (OC), and/or ECA are ligated. We found that an individual O:3 LPS molecule carries either OC or O-PS substitution but not both. Related to this, we identified three genes in Y. enterocolitica O:3 that all expressed O-PS ligase activity in the Escherichia coliDeltawaaL mutant. The LPS phenotypes of Y. enterocolitica O:3 single, double and triple ligase mutants indicated that two of ligases, named as WaaL(os) and WaaL(ps) , had a preferred substrate specificity for OC and O-PS, respectively, although with some promiscuity between the ligases; the third ligase named as WaaL(xs) was not involved in LPS or ECA biosynthesis. In Y. enterocolitica O:8 the WaaL(os) homologue (Ye1727) ligated a single pentasaccharide O-unit to LA-IC suggesting that in both Y. enterocolitica O:3 and O:8 WaaL(os) is an oligosaccharide (OS)-specific ligase. Finally, Yersinia pestis and Y. pseudotuberculosis carry only the waaL(ps) gene, while either waaL(os) or waaL(xs) or both are additionally present in other Yersinia species. This is the first report on the presence of three different oligo /polysaccharide-specific ligases in a single bacterium. PMID- 22053913 TI - Glycerol conversion to 1, 3-Propanediol is enhanced by the expression of a heterologous alcohol dehydrogenase gene in Lactobacillus reuteri. AB - In this work, Lactobacillus reuteri has been metabolically engineered for improving 1, 3-propanediol (1, 3-PD) production by the expression of an Escherichia coli alcohol dehydrogenase, yqhD, that is known to efficiently convert the precursor 3-hydroxypropionaldehyde (3-HPA) to 1, 3-PD. The engineered strain exhibited significantly altered formation rates for the product and other metabolites during the fermentation. An increase in the 1, 3-PD specific productivity of 34% and molar yield by 13% was achieved in the clone, relative to the native strain. A concomitant decrease in the levels of toxic intermediate, 3 HPA, was observed, with the specific productivity levels being 25% lesser than that of the native strain. Interestingly, the recombinant strain exhibited elevated rates of lactate and ethanol formation as well as reduced rate of acetate production, compared to the native strain. The preferential utilization of NADPH by YqhD with a possible decrease in the native 1, 3-PD oxidoreductase (NADH-dependent) activity, could have resulted in the diversion of surplus NADH towards increased lactate and ethanol productivities. PMID- 22053912 TI - Aldo-keto reductases protect lung adenocarcinoma cells from the acute toxicity of B[a]P-7,8-trans-dihydrodiol. AB - Tobacco smoke exposure stimulates the expression of genes that are likely to be involved in the metabolism of its combustion products such as polycyclic aromatic hydrocarbons (PAH). Four of the smoke induced genes are aldo-keto reductases (AKR), enzymes that metabolically activate PAH to PAH o-quinones. Alternatively, PAHs are metabolized to (+/-)-anti-diol epoxides, such as (+/-)-anti benzo[a]pyrene diol epoxide ((+/-)-anti-BPDE)), by the combined action of P4501A1/1B1 and epoxide hydrolase. (+/-)-anti-BPDE forms DNA adducts directly, while PAH o-quinones cause DNA damage by oxidative stress through a futile redox cycle. To address the role of AKRs in PAH cytotoxicity, we compared the cytotoxicity of PAH metabolites and the effects of overexpressing AKR1A1 in lung cells. (+/-)-anti-BPDE and B[a]P-7,8-trans-dihydrodiol, an intermediate in (+/-) anti-BPDE metabolism, are toxic to A549 cells at concentrations with an IC(50) of ~2 MUM. In contrast, the PAH o-quinone B[a]P-7,8-dione was about 10-fold less toxic to A549 cells with an IC(50) > 20 MUM. Similar differences in cytoxicity were observed with two other PAH o-quinones (benz[a]anthracene-3,4-dione and 7,12 dimethylbenz[a]anthracene-3,4-dione) compared with their respective diol-epoxide counterparts (BA-3,4-diol-1,2-epoxide and DMBA-3,4-diol-1,2-epoxide). In addition, both anti-BPDE and B[a]P-7,8-trans-dihydrodiol induced p53 expression ~6 h post-treatment at concentrations as low as 1 MUM consistent with extensive DNA damage. B[a]P-7,8-dione treatment did not induce p53 but generated reactive oxygen species (ROS) in A549 cells and induced the expression of oxidative response genes in H358 cells. We also observed that overexpression of AKR1A1 in H358 cells, which otherwise have low levels of AKR expression, protected cells 2 10-fold from the toxic effects of B[a]P-7,8-trans-dihydrodiol. These data suggest that overexpression of AKRs may protect lung cancer cells from the acute toxic effects of PAH. PMID- 22053914 TI - The molecular basis for the presence of two autoimmune diseases occurring simultaneously--preliminary observations based on computer analysis. AB - Specific Human Leukocyte Antigen Class II (HLA II) molecules associated with pemphigus vulgaris (PV), mucous membraine pemphigoid (MMP), and mixed connective tissue disease (MCTD) may react with multiple T cell epitopes within desmoglein 3 (Dsg 3), bullous pemphigoid antigen 2 (BPAG 2), and 70 kDa polypeptide small nuclear ribonucleoproteins (snRNP70) in autoantibody production. We report a group of patients with simultaneous occurrences of PV with MCTD, and MMP with MCTD. In one patient group, we performed serological studies to show presence of antibodies to Dsg 3, Dsg 1, and snRNP70 simultaneously. In the second group, we performed serological studies to show presence of antibodies to BPAG 1, BPAG 2, beta4 integrin, and snRNP70 simultaneously. In both groups, HLA II genes were analyzed and the observations were consistent with previously described associations with PV, MMP, and MCTD. It is possible that HLA-DQbeta1*0301 allele, present in 10 of 17 patients and DRbeta1*04 in some of the others, may have the ability to bind to several relevant T cell epitopes in the snRNP70 molecule. We have utilized a computer model to demonstrate that HLA II-restricted T cell epitopes present within the known autoantigens may be capable of eliciting an immune response. While other explanations and mechanisms exist, the authors suggest that epitope spreading may be one possible mechanism, amongst others, that may result in the simultaneous presence of two separate pathogenic autoantibodies. PMID- 22053917 TI - Covalency in the 4f shell of tris-cyclopentadienyl ytterbium (YbCp3)--a spectroscopic evaluation. AB - Evidence is presented of significant covalency in the ytterbium 4f shell of tris cyclopentadienyl ytterbium (YbCp(3)) in its electronic ground state, that can be represented by the superposition of an ionic configuration Yb(III):4f(13)(Cp(3)) and a charge-transfer configuration Yb(II):4f(14)(Cp(3))(-1). The relative weights of these configurations were determined from (i) the difference in their 4f photoionization cross sections, (ii) the accumulation of spin-density centered on the (13)C atoms of the Cp ring, as measured by a pulsed EPR (HYSCORE) experiment, (iii) the reduction in the spin-density in the 4f shell, manifest in the (171)Yb hyperfine interaction, and (iv) the principal values of the g-tensor, obtained from the EPR spectrum of a frozen glass solution at 5.4 K. Each of these methods finds that the spin density attributable to the charge transfer configuration is in the range 12-17%. The presence of configuration interaction (CI) also accounts for the highly anomalous energies, intensities, and vibronic structure in the "f-f" region of the optical spectrum, as well as the strict adherence of the magnetic susceptibility to the Curie law in the range 30-300 K. PMID- 22053918 TI - The relation of serotonin-related gene and COMT gene polymorphisms with criminal behavior in schizophrenic disorder. AB - OBJECTIVE: It has been suggested that patients with schizophrenia might be involved in criminal behavior, such as homicidal and violent behavior. However, the relationship between criminal behavior and genes in patients with schizophrenia has not been clearly elucidated. The objective of this study was to examine the relation between criminal behavior and serotonin-related gene or catechol-O-methyltransferase (COMT) gene polymorphisms in patients with schizophrenia. METHOD: Serotonin-related and COMT polymorphic markers were assessed by using single nucleotide polymorphism (SNP) genotyping. Ninety-nine crime-related inpatients with schizophrenia (57 homicidal and 42 nonhomicidal violent) and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. The genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C and COMT V158M were compared between groups. RESULTS: The TPH1 CC genotype had 2.7-fold higher odds of crime-related schizophrenia compared with A-carrier genotype after the analysis was controlled for sex and age (OR, 2.69; 95% CI, 1.22 - 5.91; P = .01). In addition, the TPH1 CC genotype had 3.4-fold higher odds of homicidal schizophrenia compared with A carrier genotype after the analysis was controlled for sex and age (OR, 3.38; 95% CI, 1.40 - 8.18; P = .007). However, no significant differences were found in the frequencies of genotype of COMT polymorphism between criminal schizophrenics and healthy subjects, nor were any significant differences found between nonhomicidal schizophrenics and healthy subjects. CONCLUSIONS: These results indicate that the TPH1 CC recessive genotype is likely to be a genetic risk factor for criminal behavior, especially homicidal behavior in patients with schizophrenia. However, COMT gene polymorphisms were not associated with criminal behavior in schizophrenic patients. PMID- 22053916 TI - Pleiotropic effects of pitavastatin. AB - 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are established first line treatments for hypercholesterolaemia. In addition to the direct effects of statins in reducing concentrations of atherogenic low density lipoprotein cholesterol (LDL-C), several studies have indicated that the beneficial effects of statins may be due to some of their cholesterol independent, multiple (pleiotropic) effects which may differ between different members of the class. Pitavastatin is a novel synthetic lipophilic statin that has a number of pharmacodynamic and pharmacokinetic properties distinct from those of other statins, which may underlie its potential pleiotropic benefits in reducing cardiovascular risk factors. This review examines the principal pleiotropic effects of pitavastatin on endothelial function, vascular inflammation, oxidative stress and thrombosis. The article is based on a systematic literature search carried out in December 2010, together with more recent relevant publications where appropriate. The available data from clinical trials and in vitro and animal studies suggest that pitavastatin is not only effective in reducing LDL-C and triglycerides, but also has a range of other effects. These include increasing high density lipoprotein cholesterol, decreasing markers of platelet activation, improving cardiac, renal and endothelial function, and reducing endothelial stress, lipoprotein oxidation and, ultimately, improving the signs and symptoms of atherosclerosis. It is concluded that the diverse pleiotropic actions of pitavastatin may contribute to reducing cardiovascular morbidity and mortality beyond that achieved through LDL-C reduction. PMID- 22053919 TI - Hypoxia induced amoeboid microglial cell activation in postnatal rat brain is mediated by ATP receptor P2X4. AB - BACKGROUND: Activation of amoeboid microglial cells (AMC) and its related inflammatory response have been linked to the periventricular white matter damage after hypoxia in neonatal brain. Hypoxia increases free ATP in the brain and then induces various effects through ATP receptors. The present study explored the possible mechanism in ATP induced AMC activation in hypoxia. RESULTS: We first examined the immunoexpression of P2X4, P2X7 and P2Y12 in the corpus callosum (CC) and subependyma associated with the lateral ventricles where both areas are rich in AMC. Among the three purinergic receptors, P2X4 was most intensely expressed. By double immunofluorescence, P2X4 was specifically localized in AMC (from P0 to P7) but the immunofluorescence in AMC was progressively diminished with advancing age (P14). It was further shown that P2X4 expression was noticeably enhanced in P0 day rats subjected to hypoxia and killed at 4, 24, 72 h and 7 d versus their matching controls by double labeling and western blotting analysis. P2X4 expression was most intense at 7 d whence the inflammatory response was drastic after hypoxia. We then studied the association of P2X4 with cytokine release in AMC after hypoxic exposure. In primary microglial cells exposed to hypoxia, IL 1beta and TNF-alpha protein levels were up-regulated. Blockade of P2X4 receptor with 2', 3'-0-(2, 4, 6-Trinitrophenyl) adenosine 5'-triphosphate, a selective P2X1-7 blocker resulted in partial suppression of IL-1beta (24% vs hypoxic group) and TNF-alpha expression (40% vs hypoxic group). However, pyridoxal phosphate-6 azo (benzene-2, 4-disulfonic acid) tetrasodium salt hydrate, a selective P2X1-3, 5-7 blocker did not exert any significant effect on the cytokine expression. CONCLUSIONS: It is concluded that P2X4 which is constitutively expressed by AMC in postnatal rats was enhanced in hypoxia. Hypoxia induced increase in IL-1beta and TNF-alpha expression was reversed by 2', 3'-0-(2, 4, 6-Trinitrophenyl) adenosine 5'-triphosphate suggesting that P2X4 mediates ATP induced AMC activation and its production of proinflammatory cytokines. PMID- 22053920 TI - Health care help seeking behaviour among prisoners in Norway. AB - BACKGROUND: Prisoners are associated with high health care needs compared with the general population. This study aims to investigate prisoners' use of health service. METHODS: A cross-sectional study of 29 prisons in central and southern parts of Norway. A questionnaire was distributed to 1, 454 prisoners (90% response rate). Multilevel analyses were employed to analyse help seeking behaviour among the prisoners. RESULTS: Help seeking was substantially associated with sleep problems and drug problems. There was also a tendency for closed prisons as well as high staffing levels of healthcare professionals to be associated with elevated health care use. CONCLUSIONS: This study suggests that sleep problems and drug use are most frequently associated with health service use. The differences in health care use between prisons suggest that the implementation of prison health care standards should be addressed. PMID- 22053921 TI - Effects of regular or irregular event schedules on cerebral hemovelocity during a sustained attention task. AB - Transcranial Doppler sonography was used to measure bilateral cerebral blood flow velocity during sustained attention task performance where the background event schedule occurred in a synchronous (temporally regular) or asynchronous (temporally irregular) manner. Perceptual sensitivity was greater in the synchronous case and declined over time in both conditions. Blood flow velocity was greater in the more difficult asynchronous condition and declined over time in both conditions in the right hemisphere, but the decline in blood flow velocity was limited to the asynchronous condition in the left hemisphere. The results are interpreted in terms of a resource model of sustained attention. PMID- 22053922 TI - Impact of pathological tumor stage for salvage radiotherapy after radical prostatectomy in patients with prostate-specific antigen < 1.0 ng/ml. AB - BACKGROUND: To evaluate prognostic factors in salvage radiotherapy (RT) for patients with pre-RT prostate-specific antigen (PSA) < 1.0 ng/ml. METHODS: Between January 2000 and December 2009, 102 patients underwent salvage RT for biochemical failure after radical prostatectomy (RP). Re-failure of PSA after salvage RT was defined as a serum PSA value of 0.2 ng/ml or more above the postradiotherapy nadir followed by another higher value, a continued rise in serum PSA despite salvage RT, or initiation of systemic therapy after completion of salvage RT. Biochemical relapse-free survival (bRFS) was estimated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: The median follow-up period was 44 months (range, 11-103 months). Forty-three patients experienced PSA re-failure after salvage RT. The 4-year bRFS was 50.9% (95% confidence interval [95% CI]: 39.4-62.5%). In the log-rank test, pT3-4 (p < 0.001) and preoperative PSA (p = 0.037) were selected as significant factors. In multivariate analysis, only pT3-4 was a prognostic factor (hazard ratio: 3.512 [95% CI: 1.535-8.037], p = 0.001). The 4-year bRFS rates for pT1-2 and pT3-4 were 79.2% (95% CI: 66.0-92.3%) and 31.7% (95% CI: 17.0-46.4%), respectively. CONCLUSIONS: In patients who have received salvage RT after RP with PSA < 1.0 ng/ml, pT stage and preoperative PSA were prognostic factors of bRFS. In particular, pT3-4 had a high risk for biochemical recurrence after salvage RT. PMID- 22053923 TI - High-risk human papillomavirus associated with incident cervical intraepithelial neoplasia developing in mothers in the Finnish Family HPV Study cohort. AB - BACKGROUND: Cofactors of high-risk (HR) human papillomavirus (HPV) in the progression of cervical intraepithelial neoplasia (CIN) are incompletely characterized. In this study these cofactors were investigated in a longitudinal setting. METHODS: A cohort of 329 women (mean age 25.5 y) were enrolled in the Finnish Family HPV Study, and followed-up for 6 y with serial cervical samples for HPV genotyping, virus integration status, and HPV serology. Hospital records were reviewed until March 2010 and linked with HPV detection data. All incident CIN lesions were subjected to HPV genotyping. HPV covariates were studied in an age- and HPV-matched nested case-control (1:4) setting. RESULTS: Twelve of the 329 women developed an incident CIN: 2 CIN1, 3 CIN2, and 7 CIN3. HPV16 was detected most frequently (7/12), followed by HPV58 (2/12), HPV18, HPV31, and HPV42. HPV integration was present in 4/12 cases. Long-lasting persistence of HPV31 and HPV16 preceded incident CIN2 and CIN3. In multivariate conditional logistic regression, the risk for incident CIN increased up to 4-fold with increasing number of deliveries (p = 0.024) and decreased with history of genital warts (p = 0.036). CONCLUSION: Baseline HR-HPV infections and their persistence precede incident CIN by several years. The 2 independent covariates of HR-HPV were (1) number of deliveries (increasing the risk), and (2) history of genital warts (protective effect). PMID- 22053924 TI - Palladium-catalyzed direct olefination of urea derivatives with n-butyl acrylate by C-H bond activation under mild reaction conditions. AB - Pd(II)-catalyzed aromatic C-H bond activation using urea as a directing group was achieved in a p-TsOH/AcOH medium under mild reaction conditions. The direct olefination products of various urea derivatives were produced from aryl urea derivatives and butyl acrylate in moderate to good yields. PMID- 22053925 TI - Equilibrium contact angles of liquid droplets on ideal rough solids. AB - This work proposes a theoretical model for predicting the apparent equilibrium contact angle of a liquid on an ideal rough surface that is homogeneous and has a negligible body force, line tension, or contact angle hysteresis between solid and liquid. The model is derived from the conservation equations and the free energy minimization theory for the changes of state of liquid droplets. The work of adhesion is expressed as the contact angles in the wetting process of the liquid droplets. Equilibrium contact angles of liquid droplets for rough surfaces are expressed as functions of the area ratios for the solid, liquid, and surrounding gas and the roughness ratio and wetting ratio of the liquid on the solid for the partially and fully wet states. It is found that the ideal critical angle for accentuating the contact angles by the surface roughness is 48 degrees . The present model is compared with existing experimental data and the classical Wenzel and Cassie-Baxter models and agrees with most of the experimental data for various surfaces and liquids better than does the Wenzel model and accounts for trends that the Wenzel model cannot explain. PMID- 22053926 TI - Low-loss, high-permittivity composites made from graphene nanoribbons. AB - A new composite material was prepared by incorporation of graphene nanoribbons into a dielectric host matrix. The composite possesses remarkably low loss at reasonably high permittivity values. By varying the content of the conductive filler, one can tune the loss and permittivity to desirable values over a wide range. The obtained data exemplifies how nanoscopic changes in the structure of conductive filler can affect macroscopic properties of composite material. PMID- 22053927 TI - Reviews on animal diseases recently published in other journals. PMID- 22053930 TI - The honeymoon phase and studies of nonsimultaneous chains in kidney-paired donation. PMID- 22053929 TI - Origin and consequences of brain Toll-like receptor 4 pathway stimulation in an experimental model of depression. AB - BACKGROUND: There is a pressing need to identify novel pathophysiological pathways relevant to depression that can help to reveal targets for the development of new medications. Toll-like receptor 4 (TLR-4) has a regulatory role in the brain's response to stress. Psychological stress may compromise the intestinal barrier, and increased gastrointestinal permeability with translocation of lipopolysaccharide (LPS) from Gram-negative bacteria may play a role in the pathophysiology of major depression. METHODS: Adult male Sprague Dawley rats were subjected to chronic mild stress (CMS) or CMS+intestinal antibiotic decontamination (CMS+ATB) protocols. Levels of components of the TLR-4 signaling pathway, of LPS and of different inflammatory, oxidative/nitrosative and anti-inflammatory mediators were measured by RT-PCR, western blot and/or ELISA in brain prefrontal cortex. Behavioral despair was studied using Porsolt's test. RESULTS: CMS increased levels of TLR-4 and its co-receptor MD-2 in brain as well as LPS and LPS-binding protein in plasma. In addition, CMS also increased interleukin (IL)-1beta, COX-2, PGE2 and lipid peroxidation levels and reduced levels of the anti-inflammatory prostaglandin 15d-PGJ2 in brain tissue. Intestinal decontamination reduced brain levels of the pro-inflammatory parameters and increased 15d-PGJ2, however this did not affect depressive-like behavior induced by CMS. CONCLUSIONS: Our results suggest that LPS from bacterial translocation is responsible, at least in part, for the TLR-4 activation found in brain after CMS, which leads to release of inflammatory mediators in the CNS. The use of Gram-negative antibiotics offers a potential therapeutic approach for the adjuvant treatment of depression. PMID- 22053931 TI - Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin. AB - Ubiquitin conjugation (ubiquitylation) plays important roles not only in protein degradation but also in many other cellular functions. However, the sites of proteins that are targeted for such modification have remained poorly characterized at the proteomic level. We have now developed a method for the efficient identification of ubiquitylation sites in target proteins with the use of an engineered form of ubiquitin (K0-Ub), in which all seven lysine residues are replaced with arginine. K0-Ub is covalently attached to lysine residues of target proteins via an isopeptide bond, but further formation of a polyubiquitin chain does not occur on K0-Ub. We identified a total of 1392 ubiquitylation sites of 794 proteins from HEK293T cells. Profiling of ubiquitylation sites indicated that the sequences surrounding lysine residues targeted for ubiquitin conjugation do not share a common motif or structural feature. Furthermore, we identified a critical ubiquitylation site of the cyclin-dependent kinase inhibitor p27(Kip1). Mutation of this site thus inhibited ubiquitylation of and stabilized p27(Kip1), suggesting that this lysine residue is the target site of p27(Kip1) for ubiquitin conjugation in vivo. In conclusion, our method based on K0-Ub is a powerful tool for proteome-wide identification of ubiquitylation sites of target proteins. PMID- 22053932 TI - Structurally flexible triethanolamine core PAMAM dendrimers are effective nanovectors for DNA transfection in vitro and in vivo to the mouse thymus. AB - With the aim of developing dendrimer nanovectors with a precisely controlled architecture and flexible structure for DNA transfection, we designed PAMAM dendrimers bearing a triethanolamine (TEA) core, with branching units pointing away from the center to create void spaces, reduce steric congestion, and increase water accessibility for the benefit of DNA delivery. These dendrimers are shown to form stable nanoparticles with DNA, promote cell uptake mainly via macropinocytosis, and act as effective nanovectors for DNA transfection in vitro on epithelial and fibroblast cells and, most importantly, in vivo in the mouse thymus, an exceedingly challenging organ for immune gene therapy. Collectively, these results validate our rational design approach of structurally flexible dendrimers with a chemically defined structure as effective nanovectors for gene delivery, and demonstrate the potential of these dendrimers in intrathymus gene delivery for future applications in immune gene therapy. PMID- 22053933 TI - Infrared (810 nm) low-level laser therapy in experimental model of strain-induced skeletal muscle injury in rats: effects on functional outcomes. AB - Muscle strains are among the most prevalent causes for athletes' absence from sport activities. Low-level laser therapy (LLLT) has recently emerged as a potential contender to nonsteroidal anti-inflammatory drugs in muscle strain treatment. In this work we investigated effects of LLLT and diclofenac on functional outcomes in the acute stage after muscle strain injury in rats. Muscle strain was induced by overloading the tibialis anterior muscle of rats during anesthesia. The injured groups received either no treatment, or a single treatment with diclofenac 30 min prior to injury, or LLLT (810 nm, 100 mW) with doses of 1, 3, 6 or 9 J, at 1 h after injury. Functional outcome measures included a walking index and assessment of electrically induced muscle performance. All treatments (except 9 J LLLT) significantly improved the walking index 12 h postinjury compared with the untreated group. The 3 J group also showed a significantly better walking index than the drug group. All treatments significantly improved muscle performance at 6 and 12 h. LLLT dose of 3 J was as effective as the pharmacological agent in improving functional outcomes in the early phase after a muscle strain injury in rats. PMID- 22053934 TI - The crystal structure of AphB, a virulence gene activator from Vibrio cholerae, reveals residues that influence its response to oxygen and pH. AB - Expression of the two critical virulence factors of Vibrio cholerae, toxin coregulated pilus and cholera toxin, is initiated at the tcpPH promoter by the regulators AphA and AphB. AphA is a winged helix DNA-binding protein that enhances the ability of AphB, a LysR-type transcriptional regulator, to activate tcpPH expression. We present here the 2.2 A X-ray crystal structure of full length AphB. As reported for other LysR-type proteins, AphB is a tetramer with two distinct subunit conformations. Unlike other family members, AphB must undergo a significant conformational change in order to bind to DNA. We have found five independent mutations in the putative ligand-binding pocket region that allow AphB to constitutively activate tcpPH expression at the non-permissive pH of 8.5 and in the presence of oxygen. These findings indicate that AphB is responsive to intracellular pH as well as to anaerobiosis and that residues in the ligand-binding pocket of the protein influence its ability to respond to both of these signals. We have solved the structure of one of the constitutive mutants, and observe conformational changes that would allow DNA binding. Taken together, these results describe a pathway of conformational changes allowing communication between the ligand and DNA binding regions of AphB. PMID- 22053937 TI - Rad Resilient City Initiative launched. PMID- 22053938 TI - State-of-the-art therapeutic medical countermeasures for viral threat agents. AB - In recent years, there has been an increase in the perceived threat of biological agents being used against civilian populations. This has prompted an urgent need for the development and procurement of medical countermeasures (MCMs) against highly pathogenic viruses that can prevent morbidity and mortality from infections caused by these agents. To date, antiviral drug development has been largely focused on clinically prevalent chronic infections due to their commercial viability. This has left a huge gap in the drug development path for acute infections of biodefense importance. In this review, we discuss the antiviral research and development initiatives focusing specifically on poxviruses, filoviruses, and equine encephalitis viruses (EEV). We discuss the benefits and technical challenges in the current development strategies and the hurdles in the licensure path for MCMs against these highly pathogenic viruses under the FDA Animal Rule, and we provide recommendations for the path forward. PMID- 22053936 TI - Application of the Hard and Soft, Acids and Bases (HSAB) theory to toxicant- target interactions. AB - Many chemical toxicants and/or their active metabolites are electrophiles that cause cell injury by forming covalent bonds with nucleophilic targets on biological macromolecules. Covalent reactions between nucleophilic and electrophilic reagents are, however, discriminatory since there is a significant degree of selectivity associated with these interactions. Over the course of the past few decades, the theory of Hard and Soft, Acids and Bases (HSAB) has proven to be a useful tool in predicting the outcome of such reactions. This concept utilizes the inherent electronic characteristic of polarizability to define, for example, reacting electrophiles and nucleophiles as either hard or soft. These HSAB definitions have been successfully applied to chemical-induced toxicity in biological systems. Thus, according to this principle, a toxic electrophile reacts preferentially with biological targets of similar hardness or softness. The soft/hard classification of a xenobiotic electrophile has obvious utility in discerning plausible biological targets and molecular mechanisms of toxicity. The purpose of this perspective is to discuss the HSAB theory of electrophiles and nucleophiles within a toxicological framework. In principle, covalent bond formation can be described by using the properties of their outermost or frontier orbitals. Because these orbital energies for most chemicals can be calculated using quantum mechanical models, it is possible to quantify the relative softness (sigma) or hardness (eta) of electrophiles or nucleophiles and to subsequently convert this information into useful indices of reactivity. This atomic level information can provide insight into the design of corroborative laboratory research and thereby help investigators discern corresponding molecular sites and mechanisms of toxicant action. The use of HSAB parameters has also been instrumental in the development and identification of potential nucleophilic cytoprotectants that can scavenge toxic electrophiles. Clearly, the difficult task of delineating molecular sites and mechanisms of toxicant action can be facilitated by the application of this quantitative approach. PMID- 22053940 TI - A simple objective evaluation and grading for facial paralysis outcomes. AB - CONCLUSION: A simple measuring box to determine lip-shift angle and eye-width narrowing offered simultaneous and objective data on outcome dysfunction. The method is as easy as visual approaches. The method is objective and as easy as visual access. It is practical for routine clinical use in any clinic. OBJECTIVES: The outcome dysfunction after facial paralysis is commonly evaluated by subjective visual access. This paper introduces a new method for simple objective evaluation and grading with documentation of lip-shift and eye-width changes. METHODS: Thirty adult controls were used to determine standard deviations (SDs) for angular shift of the lip at rest and eye-width narrowing at maximum lip protrusion. Thirty patients with facial paralysis more than 6 months after onset were studied for outcomes in terms of synkinesis, contracture, and lip deviation to the healthy side. Abnormalities were read with a simple measuring box. RESULTS: Among the controls, mean lip shift at rest and its SD were 0 degrees and 1.2. Mean eye narrowing at maximum lip protrusion effort and its SD were -0.6 mm and 1.6. This paper proposes a new grading system that relies simply on the sum of evaluating items exceeding 2 SDs, or residual lip deviation to the healthy side. PMID- 22053941 TI - Genetic variation of gamma-tocopherol methyltransferase gene contributes to elevated alpha-tocopherol content in soybean seeds. AB - BACKGROUND: Improvement of alpha-tocopherol content is an important breeding aim to increase the nutritional value of crops. Several efforts have been conducted to improve the alpha-tocopherol content in soybean [Glycine max (L.) Merr.] through transgenic technology by overexpressing genes related to alpha-tocopherol biosynthesis or through changes to crop management practices. Varieties with high alpha-tocopherol content have been identified in soybean germplasms. The heritability of this trait has been characterized in a cross between high alpha tocopherol variety Keszthelyi Aproszemu Sarga (KAS) and low alpha-tocopherol variety Ichihime. In this study, the genetic mechanism of the high alpha tocopherol content trait of KAS was elucidated. RESULTS: Through QTL analysis and fine mapping in populations from a cross between KAS and a Japanese variety Ichihime, we identified gamma-TMT3, which encodes gamma-tocopherol methyltransferase, as a candidate gene responsible for high alpha-tocopherol concentration in KAS. Several nucleotide polymorphisms including two nonsynonymous mutations were found in the coding region of gamma-TMT3 between Ichihime and KAS, but none of which was responsible for the difference in alpha tocopherol concentration. Therefore, we focused on transcriptional regulation of gamma-TMT3 in developing seeds and leaves. An F5 line that was heterozygous for the region containing gamma-TMT3 was self-pollinated. From among the progeny, plants that were homozygous at the gamma-TMT3 locus were chosen for further evaluation. The expression level of gamma-TMT3 was higher both in developing seeds and leaves of plants homozygous for the gamma-TMT3 allele from KAS. The higher expression level was closely correlated with high alpha-tocopherol content in developing seeds. We generated transgenic Arabidopsis plants harboring GUS gene under the control of gamma-TMT3 promoter from KAS or Ichihime. The GUS activity assay showed that the activity of gamma-TMT3 promoter from KAS was higher than that of Ichihime. CONCLUSIONS: The genetic variation in gamma-TMT3, which plays a major role in determining alpha-tocopherol concentration, provides significant information about the regulation of tocopherol biosynthesis in soybean seeds. This knowledge will help breeding programs to develop new soybean varieties with high alpha-tocopherol content. PMID- 22053942 TI - Association between patient beliefs regarding assigned treatment and clinical response: reanalysis of data from the Hypericum Depression Trial Study Group. AB - OBJECTIVE: To reanalyze data from a 2002 study by the Hypericum Depression Trial Study Group to determine whether patients who believed they were receiving active therapy rather than placebo obtained greater improvement, independent of treatment. METHOD: Three hundred forty adults with major depressive disorder (according to the Structured Clinical Interview for DSM-IV) and baseline scores of >= 20 on the 17-item Hamilton Depression Rating Scale (HDRS-17) were randomized to Hypericum perforatum 900-1,500 mg/d, sertraline 50-100 mg/d, or placebo and were asked to guess their assigned treatment after 8 weeks. This reanalysis of data was performed from October 1, 2009, to April 15, 2011. The intent-to-treat sample included 207 subjects (mean age = 44 years) who had (1) at least 1 postbaseline visit; (2) adherence data based on serum levels of hyperforin, sertraline, and desmethylsertraline; and (3) guess data. Univariate factorial analysis of variance was used to determine whether treatment assignment affected clinical improvement according to HDRS-17 score and whether this effect was moderated by patient guess of sertraline, Hypericum, or placebo. Analysis of covariance was used to determine whether side effects mediated improvement in the context of patient guess and assigned treatment. chi2 analyses compared response rates (>= 50% decrease in HDRS-17 score) between the guess groups and between the treatment groups within each guess group. RESULTS: Assigned treatment had no significant effect on clinical improvement (P = .65), but patient guess was significantly associated with improvement (P < .001), and treatment and guess interacted significantly (P = .005). Among subjects who guessed placebo, clinical improvement was small and did not differ significantly across treatments. Among subjects who guessed Hypericum, improvement was large and did not differ significantly across treatments. Among subjects who guessed sertraline, those who received placebo or sertraline had large improvements, but those who received Hypericum had significantly less improvement (P < .001). Similar findings were obtained for response rates. CONCLUSIONS: Patient beliefs regarding treatment may have a stronger association with clinical outcome than the actual medication received, and the strength of this association may depend upon the particular combination of treatment guessed and treatment received. PMID- 22053943 TI - Disordered spheres with extensive overlap in projection: image simulation and analysis. AB - This article simulates highly overlapped projections of spherical particles that are distributed randomly in space. The size and number of the features in the projections are examined as well as how these features change with particle size and concentration. First, there are discernable features in projection even when particles overlap extensively, and the size of these discernable features is the expected size of an individual particle. Second, the number of features increases with specimen thickness at a rate of t(0.543) when the specimen thickness is below a critical value and becomes independent of specimen thickness at higher thicknesses. A criterion is established for the critical thickness based on particle size and particle volume fraction. When the specimen thickness is known and smaller than the critical thickness, a single representative transmission electron microscopy (TEM) (or scanning TEM) image exhibiting extensive particle overlap can be used to determine the size and number density of the spherical particles. PMID- 22053945 TI - Electron affinities, well depths, and vibrational spectroscopy of cis- and trans HOCO. AB - We report vibrationally resolved photoelectron spectra of internally cold HOCO(-) and DOCO(-) anions at wavelengths near and well above the detachment threshold. These spectra are dominated by a strong Franck-Condon progression of three low energy modes of the cis isomer, the first gas-phase measurement of these vibrations. Using highly resolved, near-threshold spectra we are able to reassign the electron affinities (EAs) of cis- and trans-HOCO to 1.51 +/- 0.01 and 1.37 +/ 0.01 eV, respectively. Using these EAs, well depths with respect to OH + CO are determined to be 1.07 +/- 0.02 eV for trans-HOCO and 0.99 +/- 0.02 eV for cis HOCO. High-level ab initio calculations show excellent agreement with all experimental results. These values will be of direct use in thermochemical calculations and will help to aid in the identification of the HOCO radical in complex reactions. PMID- 22053944 TI - Development of population PK model with enterohepatic circulation for mycophenolic acid in patients with childhood-onset systemic lupus erythematosus. AB - AIM: This study aimed to develop a population pharmacokinetic (PK) enterohepatic recycling model for MPA in patients with childhood-onset systemic lupus erythematosus (cSLE). METHODS: MPA concentration-time data were from outpatients on stable oral mycophenolate mofetil (MMF) and collected under fasting conditions, with standardized meals (1 and 4 h post-dose). Sampling times were pre-dose, 20, 40 min, 1, 1.5, 2, 3, 4, 6 and 9 h, post dose. The population PK analysis simultaneously modelled MPA and 7-O-MPA-beta-glucuronide (MPAG) concentrations using nonlinear mixed effect modelling. RESULTS: PK analysis included 186 MPA and MPAG concentrations (mg l(-1)) from 19 patients. cSLE patients, age range 10-28 years, median 16.5 years were included. Mean +/- SD disease duration was 3.8 +/- 3.7 years. The final PK model included a gallbladder compartment for enterohepatic recycling and bile release time related to meal times, with first order absorption and single series of transit compartments. The PK estimates for MPA were CL(1) /F 25.3 l h(-1), V(3) /F 20.9 l, V(4) /F 234 l and CL(2) /F 19.8 l h(-1). CONCLUSION: The final model fitted the complex processes of absorption and enterohepatic circulation (EHC) in those treated with MMF for cSLE and could be applied in Bayesian dose optimization algorithms. PMID- 22053946 TI - Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation. AB - CONTEXT: Cinnamon bark is a very popular herb used in traditional medicine to treat various disorders such as chronic gastric symptoms, arthritis, and the common cold. OBJECTIVE: The immunomodulatory effect of water extract of cinnamon bark (CWE) on cytokine secretion and involvement of intracellular signaling molecules in activated T cells have been examined. MATERIALS AND METHODS: Mice were orally administered CWE for 7 days. Serum was obtained 90 min after intravenous injection of anti-CD3 antibody (Ab). Splenocytes were cultured with anti-CD3 Ab and CWE for cytokine expression, cell cycle, apoptotic/necrotic changes, and viability. IkappaBalpha, p38, JNK, ERK1/2, STAT4, and STAT6 were analyzed using western blotting. RESULTS: Administration of CWE decreased systemic levels of IFN-gamma, but not the levels of IL-4 or IL-2. In vitro, CWE inhibited anti-CD3 Ab-stimulated IFN-gamma and IL-4 at the mRNA and secreted protein levels. Despite its inhibition of IL-2 transcript, CWE enhanced IL-2 secretion. CWE treatment caused a reduction in the sub-G1 phase, accompanied by an increased ratio of apoptotic cells to necrotic cells. The increased IL-2 secretion by CWE was not mediated by its direct effect on CD4 T cells. CWE inhibited the activation of p38, JNK, ERK1/2, and STAT4, but not IkappaBalpha degradation or STAT6. DISCUSSION AND CONCLUSIONS: These observations provided evidence that CWE was able to down-regulate IFN-gamma expression in activated T cells without altering IL-2 production, involving inhibition of p38, JNK, ERK1/2, and STAT4. Our results contribute to a better understanding of the immunomodulatory action of cinnamon bark for the application of inflammatory disorders. PMID- 22053947 TI - Treatment options for subjective tinnitus: self reports from a sample of general practitioners and ENT physicians within Europe and the USA. AB - BACKGROUND: Tinnitus affects about 10-15% of the general population and risks for developing tinnitus are rising through increased exposure to leisure noise through listening to personal music players at high volume. The disorder has a considerable heterogeneity and so no single mechanism is likely to explain the presence of tinnitus in all those affected. As such there is no standardized management pathway nor singly effective treatment for the condition. Choice of clinical intervention is a multi-factorial decision based on many factors, including assessment of patient needs and the healthcare context. The present research surveyed clinicians working in six Westernized countries with the aims: a) to establish the range of referral pathways, b) to evaluate the typical treatment options for categories of subjective tinnitus defined as acute or chronic, and c) to seek clinical opinion about levels of satisfaction with current standards of practice. METHODS: A structured online questionnaire was conducted with 712 physicians who reported seeing at least one tinnitus patients in the previous three months. They were 370 general practitioners (GPs) and 365 ear-nose-throat specialists (ENTs) from the US, Germany, UK, France, Italy and Spain. RESULTS: Our international comparison of health systems for tinnitus revealed that although the characteristics of tinnitus appeared broadly similar across countries, the patient's experience of clinical services differed widely. GPs and ENTs were always involved in referral and management to some degree, but multi-disciplinary teams engaged either neurology (Germany, Italy and Spain) or audiology (UK and US) professionals. For acute subjective tinnitus, pharmacological prescriptions were common, while audiological and psychological approaches were more typical for chronic subjective tinnitus; with several specific treatment options being highly country specific. All therapy options were associated with low levels of satisfaction. CONCLUSIONS: Despite a large variety of treatment options, the low success rates of tinnitus therapy lead to frustration of physicians and patients alike. For subjective tinnitus in particular, effective therapeutic options with guidelines about key diagnostic criteria are urgently needed. PMID- 22053948 TI - Increased incidence of pregnancy complications in women who later develop scleroderma: a case control study. AB - INTRODUCTION: Studies have shown that fetal progenitor cells persist in maternal blood or bone marrow for more than 30 years after delivery. Increased trafficking of fetal cells occurs during pregnancy complications, such as hypertension, preeclampsia, miscarriage and intra-uterine growth restriction (IUGR). Women with these pregnancy complications are significantly more often HLA-class II compatible with their spouses. Women who later develop scleroderma also give birth to an HLA-class II child more often. From these prior studies we hypothesized that preeclampsia and other pregnancy complications could be associated with increased levels of fetal cell trafficking, and later be involved in the development of scleroderma. METHODS: This study was a retrospective multi centre matched case-control study. One-hundred-and-three women with systemic sclerosis (SSc) and 103 women with no history of SSc or other autoimmune disease were given a questionnaire regarding complications during pregnancy, such as hypertension, intra-uterine growth restriction (IUGR) and miscarriage. Conditional logistic regression analysis was used to assess associations. RESULTS: We found a statistically significantly increased incidence of having had a pregnancy history of hypertension or a fetus with IUGR in women who subsequently developed SSc compared to healthy controls. We found an odds ratio of 2.6 (95% confidence interval (CI): 1.1 to 4.6) for hypertensive complications during pregnancy and an odds ratio of 3.9 (95% CI: 1.2 to 12.3) for intra-uterine growth restriction for women with SSc compared to healthy controls. CONCLUSIONS: This is the first study to show an association between hypertensive complications during pregnancy or IUGR and the development of SSc at a later age. We speculate that the pregnancy abnormalities may have resulted in increased fetomaternal trafficking, which may have played a role in the increased incidence of SSc. Further studies are indicated to examine this putative relationship. PMID- 22053949 TI - Iron-catalyzed oxidation of tertiary amines: synthesis of beta-1,3-dicarbonyl aldehydes by three-component C-C couplings. AB - beta-1,3-Dicarbonyl aldehydes were synthesized by iron-catalyzed oxidative reactions between 1,3-dicarbonyl compounds and two molecules of tertiary amines in the presence of tert-butyl hydroperoxide (TBHP). alpha,beta-Unsaturated aldehydes generated by tertiary amine oxidation in situ act as key intermediates under mild reaction conditions. PMID- 22053950 TI - Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2. AB - BACKGROUND: Betaine (glycine betaine or trimethylglycine) plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS)-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2), a betaine/GABA transporter. METHODS: Mice were continuously treated with betaine for 13 days starting 1 day before they were injected with LPS, or received subacute or acute administration of betaine shortly before or after LPS injection. Then, their memory function was evaluated using Y-maze and novel object recognition tests 7 and 10-12 days after LPS injection (30 MUg/mouse, i.c.v.), respectively. In addition, mRNA expression levels in hippocampus were measured by real-time RT-PCR at different time points. RESULTS: Repeated administration of betaine (0.163 mmol/kg, s.c.) prevented LPS-induced memory impairment. GAT2 mRNA levels were significantly increased in hippocampus 24 hr after LPS injection, and administration of betaine blocked this increase. However, betaine did not affect LPS-induced increases in levels of mRNA related to inflammatory responses. Both subacute administration (1 hr before, and 1 and 24 hr after LPS injection) and acute administration (1 hr after LPS injection) of betaine also prevented LPS-induced memory impairment in the Y-maze test. CONCLUSIONS: These data suggest that betaine has protective effects against LPS induced memory impairment and that prevention of LPS-induced changes in GAT2 mRNA expression is crucial to this ameliorating effect. PMID- 22053951 TI - Comparative proteomic study reveals the involvement of diurnal cycle in cell division, enlargement, and starch accumulation in developing endosperm of Oryza sativa. AB - The development and starch accumulation of cereal endosperms rely on the sugar supply of leaves, which is subject to diurnal cycles, and the endosperm itself also experiences a light/dark switch. However, revealing how the cereal endosperm responds to diurnal input remains a major challenge. We used comparative proteomic approaches to probe diurnally affected processes in rice endosperm (Oryza sativa) 10 days after flowering under 12-h light/12-h dark. Starch granules in rice endosperm showed a growth ring structure under a normal light/dark cycle but not under constant light. Sucrose showed a high level in light and low level in dark. Two-dimensional (2-D) differential in-gel electrophoresis-based proteomic analysis revealed 101 protein spots diurnally changed and 91 identities, which were involved in diverse processes with preferred distribution in stress response, protein synthesis/destination and metabolism. Proteins involved in cell division showed high expression in light and those in cell enlargement and cell wall synthesis high in dark, while starch synthesis proteins were light-downregulated and dark-upregulated. Redox homeostasis-associated proteins showed in-phase peaks under light and dark. These data demonstrate diurnal input-regulated diverse cellular and metabolic processes in rice endosperm, and coordination among these processes is essential for development and starch accumulation with diurnal input. PMID- 22053952 TI - Three-dimensional hierarchical flowerlike alpha-Fe2O3 nanostructures: synthesis and ethanol-sensing properties. AB - The alpha-Fe(2)O(3) hierarchical nanostructures have been successfully synthesized via a simple solvothermal method. The as-prepared samples are loose and porous with flowerlike structure, and the subunits are irregularly shaped nanosheets. The morphology of the alpha-Fe(2)O(3) structures was observed to be tunable as a function of reaction time. To demonstrate the potential applications, we have fabricated a gas sensor from the as-synthesized hierarchical alpha-Fe(2)O(3) and investigated it for ethanol detection. Results show that the hierarchical alpha-Fe(2)O(3) sensor exhibits significantly improved sensor performances in comparison with the compact alpha-Fe(2)O(3) structures. The enhancement of sensing properties is attributed to the unique porous and well aligned nanostructure. PMID- 22053953 TI - Appendicular perforation at the base of the caecum, a rare operative challenge in acute appendicitis, a literature review. AB - BACKGROUND: Acute appendicitis is the most common acute surgical condition of the abdomen. Diagnosis is made based on full clinical history and examination as well as supported by a routine blood investigation and urine test. Prompt diagnosis and surgical referral may reduce the risk of perforation and prevent complications. The mortality rate of non-perforated appendicitis is less than 1 percent. Perforated appendicitis is associated with a higher mortality rate - as high as five percent and may be particularly more in extreme of age group attributed to delay in clinical presentation or diagnosis in the younger group and multiple co-morbidities in the elderly group. The aetiology is unknown. It may be linked with lack of fibre, familial tendency, or viral infection. It may be precipitated by faecaliths. The commonest site of the appendix is retrocaecal. CASE REPORT: We report a case of a 46 year old male who was admitted under the surgical service in Mid-Western Regional Hospital, Limerick with suspected appendicitis which turned out to be a perforated caecum, a rare complication of an acute appendicitis. We performed a literature review comparing two main approaches - right hemicolectomy and primary closure with omental patch - discuss and highlight their differences as well as a guide to its management. CONCLUSION: There are limited studies to compare these two surgical options in the literature. A larger prospective study is needed to compare both approaches and long term outcome. PMID- 22053955 TI - Near-infrared exposure changes cellular responses to ionizing radiation. AB - Near infrared (NIR) and X-rays are radiations from different sides of the wavelength spectrum but both are used during medical treatments, as they have severe impacts on cellular processes, including metabolism, gene expression, proliferation and survival. However, both radiations differ strictly in their consequences for exposed patients: NIR effects are generally supposed to be positive, mostly ascribed to a stimulation of metabolism, whereas X-ray leads to genetic instability, an increase of reactive oxygen species (ROS) and DNA damages and finally to cellular death by apoptosis in tumor cells. Since genomic stability after X-irradiation depends on the mitochondrial metabolism, which is well known to be regulated by NIR, we analyzed the impact of NIR on cellular responses of fibroblasts, retinal progenitor cells and keratinocytes to X radiation. Our data show that previous exposure to naturally occurring doses of nonthermal NIR combined with clinically relevant X-ray doses leads to (1) increased genomic instability, indicated by elevated ratios of mitotic catastrophes, (2) increased ROS, (3) higher amounts of X-irradiated cells entering S-phase and (4) impaired DNA double-strand break repair. Taken together, our data show tremendous effects of NIR on cellular responses to X-rays, probably affecting the results of radiotherapy after NIR exposure during cancer treatment. PMID- 22053956 TI - Sliding droplets on superomniphobic zinc oxide nanostructures. AB - This study reports on liquid-repellency of zinc oxide nanostructures (ZnO NS). The ZnO NS are synthesized by an easy and fast chemical bath deposition technique. Three different nanostructured surfaces consisting of nanorods, flowers, and particles are prepared, depending on the deposition time and the presence of ethanolamine in the reaction mixture. Chemical functionalization of the ZnO NS with 1H,1H,2H,2H-perfluorodecyltrichlorosilane (PFTS) in liquid (PFTS L) and vapor phase (PFTS V) or through octafluorobutane (C(4)F(8)) plasma deposition led to the formation of superomniphobic surfaces. A comprehensive characterization of the wetting properties (static contact angle and contact angle hysteresis) has been performed using liquids composed of deionized water and various concentrations of ethanol (surface tension between 35 and 72.6 mN/m). Depending on the nanostructures morphology, coating nature and liquid employed, high static apparent contact angles theta ~ 150-160 degrees , and low contact angle hysteresis Deltatheta ~ 0 degrees are obtained. The different ZnO NS are characterized using scanning electron microscopy (SEM) and contact angle measurements. The results reported in this work permit preparation of sliding omniphobic surfaces using a simple and low cost technique. PMID- 22053957 TI - Effects of chronic and acute oestrogen replacement therapy in aged animals after experimental stroke. AB - The effect of oestrogen replacement therapy (ERT) on stroke incidence and severity has been extensively debated. Clinical trials of ERT have demonstrated an increased risk of stroke in treated women, although the study participants were well past menopause when therapy was initiated. It has been suggested that detrimental effects of ERT may be unmasked after prolonged periods of hypoestrogenicity. To date, very few studies have examined the effect of ERT in aged animals, although the timing of replacement may be critical to the neuroprotective effects of ERT. We hypothesised that chronic ERT initiated in late middle age would decrease infarct size in the brain after an induced stroke, whereas acute ERT would have no beneficial effects in aged females. To test this hypothesis, two paradigms of ERT were administered to aged mice of both sexes aiming to determine the effects on stroke outcome and to explore the possible mechanisms by which ERT interacts with age. Female mice that received chronic ERT from 17-20 months of age showed improved stroke outcomes after experimental stroke, whereas females that had acute ERT initiated at 20 months of age did not. Chronic ERT females exhibited diminished levels of nuclear factor kappa B (NF kappaB) translocation compared to acute ERT females after stroke. Acute ERT females demonstrated both an increase in nuclear NF-kappaB and enhanced expression of pro-inflammatory cytokines. In addition, a sexual dimorphic effect of ERT was seen because males benefited from ERT, regardless of the timing of initiation. Aged males had significantly reduced expression of pro-inflammatory markers after stroke compared to age-matched females, suggesting a pro inflammatory milieu emerges with age in females. These results are consistent with the emerging clinical literature suggesting that ERT should be initiated at the time of menopause to achieve beneficial effects. The present study demonstrates the importance of using appropriate animal models in preclinical studies. PMID- 22053958 TI - Restored renal transplants from donors with distal ureteral carcinomas. PMID- 22053960 TI - Errata. PMID- 22053959 TI - Detection of internal tandem duplications in the FLT3 gene by different electrophoretic methods. AB - BACKGROUND: In acute myeloid leukemia (AML), the internal tandem duplication (ITD) in the juxtamembrane domain of the FLT3 (Fms-like tyrosine kinase 3) gene is one of the most frequent genetic alterations associated with poor prognosis. METHODS: A complex evaluation of the analytical properties of the three most frequently used detection methods--PCR followed by agarose (AGE), polyacrylamide (PAGE) or capillary electrophoresis (CE)--was performed on 95 DNA samples obtained from 73 AML patients. RESULTS: All the three methods verified the presence of a mutant allele in 20 samples from 18 patients. AGE and PAGE could detect the presence of 1%-2% mutant allele, while the detection limit of CE was 0.28%. However, acceptable reproducibility (inter-assay CV <25%) of the mutant allele rate determination was only achievable above 1.5% mutant/total allele rate. The reproducibility of the ITD size determination by CE was much better, but the ITD size calculated by PeakScanner or GeneScan analysis was 7% lower as compared to values obtained by DNA sequencing. The presence of multiple ITD was over-estimated by PAGE and AGE due to the formation of heteroduplexes. CONCLUSIONS: This study suggests the use of PCR+CE in the diagnostics and the follow-up of AML patients. The data further supports the importance of proper analytical evaluation of home-made molecular biological diagnostic tests. PMID- 22053962 TI - Community-based interference against integration of Pseudomonas aeruginosa into human salivary microbial biofilm. AB - As part of the human gastrointestinal tract, the oral cavity represents a complex biological system and harbors diverse bacterial species. Unlike the gut microbiota, which is often considered a health asset, studies of the oral commensal microbiota have been largely limited to their implication in oral conditions such as dental caries and periodontal disease. Less emphasis has been given to their potential beneficial roles, especially the protective effects against oral colonization by foreign or pathogenic bacteria. In this study, we used salivary microbiota derived from healthy human subjects to investigate protective effects against colonization and integration of Pseudomonas aeruginosa, an opportunistic bacterial pathogen, into developing or pre-formed salivary biofilms. When co-cultivated in saliva medium, P. aeruginosa persisted in the planktonic phase, but failed to integrate into the salivary microbial community during biofilm formation. Furthermore, in saliva medium supplemented with sucrose, the oral microbiota inhibited the growth of P. aeruginosa by producing lactic acid. More interestingly, while pre-formed salivary biofilms were able to prevent P. aeruginosa colonization, the same biofilms recovered from mild chlorhexidine gluconate treatment displayed a shift in microbial composition and showed a drastic reduction in protection. Our study indicates that normal oral communities with balanced microbial compositions could be important in effectively preventing the integration of foreign or pathogenic bacterial species, such as P. aeruginosa. PMID- 22053963 TI - Identification and characterization of a fibronectin-binding protein from Granulicatella adiacens. AB - The interaction of microorganisms with fibronectin plays an important role in infective endocarditis. Granulicatella adiacens is a member of the oral microbiota, formerly known as nutritionally variant streptococci, and is often isolated from endocarditis patients. In the present study we identified a surface protein, designated Cha, which binds to fibronectin, by a plaque hybridization procedure using the cshA sequence as probe, which encodes a fibronectin-binding molecule of Streptococcus gordonii DL1. The cha sequence was highly homologous to cshA and encoded a product of 2351 amino acid residues. The protein comprised a unique sequence in the N-terminal half region. The C-terminal region contained nine complete, and one incomplete, 115-amino acid residue repeat blocks. Among eight strains of nutritionally variant streptococci, three G. adiacens strains and one Abiotrophia defectiva strain carried the cha gene. Heterologous expression studies suggested that Cha adhered to immobilized fibronectin, and that this function was located in the unique region. Recombinant Cha protein also adhered to immobilize fibronectin and partially inhibited adherence of G. adiacens to fibronectin in a dose-dependent manner. These results suggest that Cha is a cell surface protein that mediates adherence of G. adiacens to fibronectin. PMID- 22053965 TI - OmpA-like protein influences cell shape and adhesive activity of Tannerella forsythia. AB - Tannerella forsythia, a gram-negative fusiform rod, is implicated in several types of oral anaerobic infections. Most gram-negative bacteria have OmpA-like proteins that are homologous to the OmpA protein in Escherichia coli. We identified an OmpA-like protein in T. forsythia encoded by the tf1331 gene as one of the major proteins by mass spectrometric analysis. Two-dimensional, diagonal electrophoresis showed that the OmpA-like protein formed a dimeric or trimeric structure via intermolecular disulfide bonds. A biotin labeling experiment revealed that a portion of the protein was exposed on the cell surface, even though T. forsythia possesses an S-layer at the outermost cell surface. Using a tf1331-deletion mutant, we showed that the OmpA-like protein affected cell morphology. The length of the mutant cell was reduced almost by half. Cell swelling was observed in more than 40% of the mutant cells. Moreover, the mutant exhibited decreased adhesion to fibronectin, retarded autoaggregation, and reduced cell surface hydrophobicity. These results suggest that the OmpA-like protein in T. forsythia plays an important role in cellular integrity and adhesive function. PMID- 22053964 TI - Filifactor alocis interactions with gingival epithelial cells. AB - An association between the gram-positive anaerobe Filifactor alocis and periodontal disease has recently emerged; however, possible pathogenic mechanisms have not been investigated. In this study we examined the responses of primary cultures of gingival epithelial cells (GECs) to infection with F. alocis. Secretion of the pro-inflammatory cytokines interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha from GECs was stimulated by F. alocis infection. F. alocis also induced apoptosis in GECs through pathways that involved caspase-3 but not caspase-9. Apoptosis was coincident with inhibition of mitogen-activated protein kinase kinase (MEK) activation. These results show that F. alocis has characteristics in common with established periodontal pathogens and has the potential to contribute to periodontal tissue destruction. PMID- 22053966 TI - Differential expression and adherence of Porphyromonas gingivalis FimA genotypes. AB - Porphyromonas gingivalis is a primary pathogen involved in the initiation and progression of adult chronic periodontitis. Its colonization on oral surfaces is a necessary first step leading to infection. FimA, a subunit protein of major (long) fimbriae, is a well-known virulence factor. Based on its nucleotide sequence, FimA is classified into several genotypes. We compared here the transcriptional levels of the fimA gene in several P. gingivalis strains using real-time polymerase chain reaction analysis, fimbrial display on the P. gingivalis surface using transmission electronic microscopy, and the adherence competencies of P. gingivalis strains carrying different types of FimAs towards saliva and Streptococcus gordonii surfaces using mutagenesis analysis. We demonstrated differential expression of each fimA gene in these P. gingivalis strains. A correlation of the transcription level of fimA and binding activity of P. gingivalis was revealed. We show that P. gingivalis strains with genotype I and II of FimA are efficient in interaction with saliva or S. gordonii. This work highlights the important role of FimA type I and II in P. gingivalis attachment to oral surfaces. PMID- 22053967 TI - The 2011 Nobel Prize--honoring the memory of Dr. Ralph Steinman. PMID- 22053968 TI - In this issue--engineering the immune system to fight cancer and infections. AB - As the immune system essentially evolved to fight off or keep at bay life threatening infectious agents rather than cancer, the question remains as to how to best redeploy it for the treatment of a broader range of diseases. This is reflected by an unprecedented diversification of platform technologies in development, facilitated by rapid progress in biotechnology. In this issue, we host several contributions outlining major efforts in developing novel immune interventions spanning antigen-specific vaccination, non-antigen-targeted immune intervention, genetically engineered lymphocytes, and ultraspecific antigen targeted ligands. In addition, the journal is hosting in this issue, two reviews discussing the complex matter and dynamic balance between immunity and viral infections, as the concept of fine modulation of that balance still carries the promise of yielding novel therapies. PMID- 22053969 TI - Antigen-specific versus antigen-nonspecific immunotherapeutic approaches for human melanoma: the need for integration for optimal efficacy? AB - Due to its immunogenecity and evidence of immune responses resulting in tumor regression, metastatic melanoma has been the target for numerous immunotherapeutic approaches. Unfortunately, based on the clinical outcomes, even the successful induction of tumor-specific responses does not correlate with efficacy. Immunotherapies can be divided into antigen-specific approaches, which seek to induce T cells specific to one or several known tumor associated antigens (TAA), or with antigen-nonspecific approaches, which generally activate T cells to become nonspecifically lytic effectors. Here the authors critically review the different immunotherapeutic approaches in melanoma. PMID- 22053970 TI - Chimeric antigen receptors in cancer immuno-gene therapy: current status and future directions. AB - The concept of chimeric antigen receptors (CARs) as molecules able to redirect T lymphocytes toward tumor cells is currently being exploited in the field of cancer immunotherapy. Despite promising preliminary results, some clinical trials evidenced limitations for this technology that must be overcome for more extensive application of CARs in tumor immunotherapy. We describe here the fundaments of these molecules in terms of structure, function, possible targets and pre-clinical and clinical applications. We also discuss strategies that can potentially overcome the limitations seen so far, paving the road to a wider application of this exciting new technology. PMID- 22053971 TI - Expanding the targets available to therapeutic antibodies via novel disease specific markers. AB - The development of immunotherapies offers significant promise for clinical applications in cancer and infectious diseases. Here the authors describe a novel, integrated approach to immunotherapy that combines novel technologies to discover and target disease-specific peptide/HLA class I complexes. This unique class of markers makes the entire proteome accessible to antibody reagents and offers unsurpassed specificity for targeting cancerous and infected cells. Arm one of the three-armed approach uses an innovative technology for the efficient, direct discovery of new peptide/HLA class I markers. Arm two applies a powerful and inventive strategy to generate T-cell receptor mimics (TCRms), which are antibodies with exquisite binding specificity for peptide/HLA class I markers, and uses TCRms to validate the specific expression of markers on cancerous and infected cells. The third arm uses TCRms to target and kill diseased cells with high sensitivity and specificity. In summary, the combination of two pioneering technologies expands the repertoire of disease-specific markers that can be targeted by therapeutic antibodies and enables a powerful, integrated approach to HLA-based immunotherapy. PMID- 22053972 TI - TCR-like biomolecules target peptide/MHC Class I complexes on the surface of infected and cancerous cells. AB - The human leukocyte antigen (HLA; also called major histocompatibility, or MHC) class I system presents peptides that distinguish healthy from diseased cells. Therefore, the discovery of peptide/MHC class I markers can provide highly specific targets for immunotherapy. Over the course of almost two decades, various strategies have been used, with mixed success, to produce antibodies that have recognition specificity for unique peptide/MHC class I complexes that mark infected and cancerous cells. Using these antibody reagents, novel peptide/MHC class I targets have been directly validated on diseased cells and new insight has been gained into the mechanisms of antigen presentation. More recently, these antibodies have shown promise for clinical applications such as therapeutic targeting of cancerous and infected cells and diagnosis and imaging of diseased cells. In this review, the authors comprehensively describe the methods used to identify disease-specific peptide/MHC class I epitopes and generate antibodies to these markers. Finally, they offer several examples that illustrate the promise of using these antibodies as anti-cancer agents. PMID- 22053974 TI - CCL5: a double-edged sword in host defense against the hepatitis C virus. AB - C-C motif ligand 5 (CCL5) facilitates induction of chemotaxis in immune cells and activation of hepatic stellate cells (HSC) at sites of liver inflammation during chronic hepatitis C virus (HCV) infection. Importantly, CCL5 participates in the establishment of T-helper 1 responses crucial in controlling liver disease and HCV infection outcome and demonstrates distinct gene expression patterns between the blood and the liver, stressing the importance of immunoregulatory networks differentially functioning between these compartments. This review illustrates the significance of CCL5-dependent pathways in HCV-related immunopathogenesis by elaborating on biological mechanisms interconnecting peripheral and tissue immunology, liver pathology, HSC activation, and interferon-alpha immunotherapy. PMID- 22053975 TI - Evaluation of the implanted cochlear implant electrode by CT scanning with three dimensional reconstruction. AB - CONCLUSIONS: Computed tomography (CT) scan with three-dimensional (3D) reconstruction of the inner ear provides a more accurate image of the relationship of the electrode within the cochlear canal, with direct demonstration of electrode insertion depth in the cochlea in comparison with X ray plain film. OBJECTIVE: This study was designed to evaluate the value of spiral CT scans with 3D reconstruction in determining the insertion site and depth of implanted cochlear implant electrodes. METHODS: A total of 172 cochlear implant recipients were involved in this study. The implanted electrodes of all patients were examined by X-ray plain film, and 157 cochlear recipients were examined by spiral CT scans with axial 1 mm image slices. The data from the CT scans were transferred to a workstation for 3D reconstruction (direct volume rendering) of the inner ear. The pseudocolor technique was used to display the electrode. RESULTS: The insertion depth of the electrode could be evaluated indirectly by the X-ray plain film. In contrast, the stereoscopic images from a CT scan with 3D reconstruction of the inner ear demonstrated the shape, position, and insertion depth of the electrode more accurately. PMID- 22053976 TI - Hypothiocyanous acid: benign or deadly? AB - Hypothiocyanous acid (HOSCN) is produced in biological systems by the peroxidase catalyzed reaction of thiocyanate (SCN(-)) with H(2)O(2). This oxidant plays an important role in the human immune system, owing to its potent bacteriostatic properties. Significant amounts of HOSCN are also formed by immune cells under inflammatory conditions, yet the reactivity of this oxidant with host tissue is poorly characterized. Traditionally, HOSCN has been viewed as a mild oxidant, which is innocuous to mammalian cells. Indeed, recent studies show that the presence of SCN(-) in airways has a protective function, by preventing the formation of other, more damaging, inflammatory oxidants. However, there is an increasing body of evidence that challenges this dogma, showing that the selectivity of HOSCN for specific thiol-containing cellular targets results in the initiation of significant cellular damage. This propensity to induce cellular dysfunction is gaining considerable interest, particularly in the cardiovascular field, as smokers have elevated plasma SCN(-), the precursor for HOSCN. This review will outline the beneficial and detrimental aspects of HOSCN formation in biological systems. PMID- 22053973 TI - The tug-of-war between dendritic cells and human chronic viruses. AB - The human immune system is under constant challenge from many viruses, some of which the body is successfully able to clear. Other viruses have evolved to escape the host immune responses and thus persist, leading to the development of chronic diseases. Dendritic cells are professional antigen-presenting cells that play a major role in both innate and adaptive immunity against different pathogens. This review focuses on the interaction of different chronic viruses with dendritic cells and the viruses' ability to exploit this critical cell type to their advantage so as to establish persistence within the host. PMID- 22053977 TI - ARVCF genetic influences on neurocognitive and neuroanatomical intermediate phenotypes in Chinese patients with schizophrenia. AB - OBJECTIVE: There are notable similarities between velocardiofacial syndrome and schizophrenia in terms of neurocognitive deficits and brain structural abnormalities. These similarities have supported the role of the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) as a susceptibility gene in schizophrenia. This study investigated the relationships between haplotypes of the ARVCF gene and specific intermediate phenotypes in schizophrenia. We hypothesized that ARVCF gene haplotypes influence caudate nucleus volume, fractional anisotropy, and neurocognitive functioning in schizophrenia. METHOD: Between May 2006 and November 2009, 200 Chinese participants (125 patients with DSM-IV diagnosis of schizophrenia and 75 controls) were genotyped using blood samples, and a subset of 166 participants (99 patients with DSM-IV diagnosis of schizophrenia and 67 controls) underwent structural magnetic resonance imaging, diffusion tensor imaging, and completed neuropsychological testing. RESULTS: The haplotype T-G-A-T-T-G-G-C-T-G-T (ARVCF-Hap1) was significantly associated with fractional anisotropy of the caudate nucleus and executive functioning in patients. Specifically, patients with more copies of ARVCF-Hap1 have lower white matter integrity in caudate nucleus (P = .0008) and greater perseverative errors (P = .00003) on the Wisconsin Card Sorting Test. A trend of lower caudate volume (P = .015) in patients with more copies of ARVCF-Hap1 was also observed. CONCLUSIONS: These findings are consistent with known ARVCF gene effects on neurodevelopment in terms of cellular arrangement, migration, and intracellular signaling involving the striatum and may involve interactions with other brain networks such as prefrontal cortex, and they underscore the importance of imaging genetic studies to elucidate the genetic influences underlying intermediate phenotypes in complex neurobehavioral disorders. PMID- 22053979 TI - Precursors of adrenomedullin, endothelin and atrial natriuretic peptide as diagnostic markers of neonatal infection. AB - AIM: To evaluate the serum levels of three precursors of vasoactive peptide as diagnostic markers for neonatal infections. METHODS: Overall, 356 neonates (160 without infection, 114 with mild infections and 82 with severe infections) were enrolled in this study. Their serum levels of mid-regional pro-adrenomedullin (MR pro-ADM), C-terminal pro-endothelin-1 (CT-pro-ET-1) and mid-regional pro-atrial natriuretic peptide (MR-pro-ANP) were measured by immunoassay, and receiver operating curve analysis was performed for each biomarker to evaluate their diagnostic values for neonatal infection. RESULTS: The serum levels of MR-pro-ADM (2.079 +/- 1.195 nM), CT-pro-ET-1 (109.4 +/- 62.9 pM) and MR-pro-ANP (1221.4 +/- 725.0 pM) in the severe infection group were significantly higher than those in the mild infection group (1.025 +/- 0.421 nM, 86.7 +/- 51.8 pM, and 687.6 +/- 575.7 pM, respectively) and in the non-infection group (0.853 +/- 0.488 nM, 51.3 +/- 40.6 pM, and 943.3 +/- 847.3 pM, respectively) (p < 0.01-0.001). Their areas under the curve were 0.72, 0.76 and 0.61, respectively. Among them, CT-pro-ET-1 had the highest sensitivity (82.65%), whereas MR-pro-ADM had the highest specificity (86.25%). CONCLUSIONS: MR-pro-ADM, CT-pro-ET-1 and MR-pro-ANP may serve as useful laboratory markers to indicate bacterial infection in neonates. PMID- 22053980 TI - Adolescent amphetamine exposure elicits dose-specific effects on monoaminergic neurotransmission and behaviour in adulthood. AB - Despite the growing non-medical consumption of amphetamine (Amph) during adolescence, its long-term neurobiological and behavioural effects have remained largely unexplored. The present research sought to characterize the behavioural profile and electrophysiological properties of midbrain monoaminergic neurons in adult rodents after Amph exposure during adolescence. Adolescent rats were administered vehicle, 0.5, 1.5, or 5.0 mg/kg.d Amph from postnatal day (PND) 30 50. At adulthood (PND 70), rats were tested in an open-field test (OFT) and elevated plus maze (EPM), paralleled by in-vivo extracellular recordings of serotonin (5-HT), dopamine (DA) and norepinephrine (NE) neurons from the dorsal raphe nucleus, ventral tegmental area, and locus coeruleus, respectively. 5-HT firing in adulthood was increased in rats that had received Amph (1.5 mg/kg.d) during adolescence. At this regimen, DA firing activity was increased, but not NE firing. Conversely, the highest Amph dose regimen (5.0 mg/kg.d) enhanced NE firing, but not DA or 5-HT firing rates. In the OFT, Amph (1.5 mg/kg.d) significantly increased the total distance travelled, while the other doses were ineffective. In the EPM, all three Amph doses increased time spent in the open arms and central platform, as well as the number of stretch-attend postures made. Repeated adolescent exposure to Amph differentially augments monoaminergic neuronal firing in a dose-specific fashion in adulthood, with corresponding alterations in locomotion, risk assessment (stretch-attend postures and central platform occupancy) and risk-taking behaviours (open-arm exploration). Thus, adolescent Amph exposure induces long-lasting neurophysiological alterations that may have implications for drug-seeking behaviour in the future. PMID- 22053981 TI - Impact of physical fitness and biometric data on the quality of external chest compression: a randomised, crossover trial. AB - BACKGROUND: During circulatory arrest, effective external chest compression (ECC) is a key element for patient survival. In 2005, international emergency medical organisations changed their recommended compression-ventilation ratio (CVR) from 15:2 to 30:2 to acknowledge the vital importance of ECC. We hypothesised that physical fitness, biometric data and gender can influence the quality of ECC. Furthermore, we aimed to determine objective parameters of physical fitness that can reliably predict the quality of ECC. METHODS: The physical fitness of 30 male and 10 female healthcare professionals was assessed by cycling and rowing ergometry (focussing on lower and upper body, respectively). During ergometry, continuous breath-by-breath ergospirometric measurements and heart rate (HR) were recorded. All participants performed two nine-minute sequences of ECC on a manikin using CVRs of 30:2 and 15:2. We measured the compression and decompression depths, compression rates and assessed the participants' perception of exhaustion and comfort. The median body mass index (BMI; male 25.4 kg/m2 and female 20.4 kg/m2) was used as the threshold for subgroup analyses of participants with higher and lower BMI. RESULTS: HR during rowing ergometry at 75 watts (HR75) correlated best with the quality of ECC (r = -0.57, p < 0.05). Participants with a higher BMI and better physical fitness performed better and showed less fatigue during ECC. These results are valid for the entire cohort, as well as for the gender-based subgroups. The compressions of female participants were too shallow and more rapid (mean compression depth was 32 mm and rate was 117/min with a CVR of 30:2). For participants with a lower BMI and higher HR75, the compression depth decreased over time, beginning after four minutes for the 15:2 CVR and after three minutes for the 30:2 CVR. Although found to be more exhausting, a CVR of 30:2 was rated as being more comfortable. CONCLUSION: The quality of the ECC and fatigue can both be predicted by BMI and physical fitness. An evaluation focussing on the upper body may be a more valid predictor of ECC quality than cycling based tests. Our data strongly support the recommendation to relieve ECC providers after two minutes. PMID- 22053982 TI - CD200-CD200R dysfunction exacerbates microglial activation and dopaminergic neurodegeneration in a rat model of Parkinson's disease. AB - BACKGROUND: Increasing evidence suggests that microglial activation may participate in the aetiology and pathogenesis of Parkinson's disease (PD). CD200 CD200R signalling has been shown to be critical for restraining microglial activation. We have previously shown that expression of CD200R in monocyte derived macrophages, induced by various stimuli, is impaired in PD patients, implying an intrinsic abnormality of CD200-CD200R signalling in PD brain. Thus, further in vivo evidence is needed to elucidate the role of malfunction of CD200 CD200R signalling in the pathogenesis of PD. METHODS: 6-hydroxydopamine (6-OHDA) lesioned rats were used as an animal model of PD. CD200R-blocking antibody (BAb) was injected into striatum to block the engagement of CD200 and CD200R. The animals were divided into three groups, which were treated with 6-OHDA/Veh (PBS), 6-OHDA/CAb (isotype control antibody) or 6-OHDA/BAb, respectively. Rotational tests and immunohistochemistry were employed to evaluate motor deficits and dopaminergic neurodegeneration in animals from each group. HPLC analysis was used to measure monoamine levels in striatum. Morphological analysis and quantification of CD11b- (or MHC II-) immunoreactive cells were performed to investigate microglial activation and possible neuroinflammation in the substantia nigra (SN). Finally, ELISA was employed to assay protein levels of proinflammatory cytokines. RESULTS: Compared with 6-OHDA/CAb or 6-OHDA/Veh groups, rats treated with 6-OHDA/BAb showed a significant increase in counts of contralateral rotation and a significant decrease in TH-immunoreactive (TH-ir) neurons in SN. A marked decrease in monoamine levels was also detected in 6 OHDA/BAb-treated rats, in comparison to 6-OHDA/Veh-treated ones. Furthermore, remarkably increased activation of microglia as well as up-regulation of proinflammatory cytokines was found concomitant with dopaminergic neurodegeneration in 6-OHDA/BAb-treated rats. CONCLUSIONS: This study shows that deficits in the CD200-CD200R system exacerbate microglial activation and dopaminergic neurodegeneration in a 6-OHDA-induced rat model of PD. Our results suggest that dysfunction of CD200-CD200R signalling may be involved in the aetiopathogenesis of PD. PMID- 22053983 TI - Top-down synthesis of versatile polyaspartamide linkers for single-step protein conjugation to materials. AB - Materials used in various biological applications are often modified with proteins to regulate biomolecular and cellular adhesion. Conventional strategies of protein conjugation accompany monovalent bifunctional protein linkers, which present several limitations in molecular synthesis and protein conjugation. Herein, we present a new strategy of preparing multivalent polyaspartamide linkers in a simple top-down manner, and also demonstrate that the resulting polymer linkers allow us to readily conjugate proteins to both organic and inorganic materials. The top-down synthesis of polyaspartamide linkers was performed by partially opening succinimidyl ring moieties of polysuccinimide (PSI) with the controlled number of nucleophiles reactive to photo-cross-linked hydrogel or gold-coated inorganic materials: (1) Poly(2-hydroxyethyl-co-2 methacryloxyethyl aspartamide) (PHMAA) presenting methacrylate was used to micropattern fibronectin or collagen on a hydrogel in order to regulate cell adhesion and growth area on a micrometer scale. (2) Poly(2-hydroxyethyl-co-2 mercaptoethyl aspartamide) (PHMCA) presenting thiol functional groups was used to link fibronectin to a gold-coated silicon microelectromechanical probe designed to measure cell traction force. Overall, these multivalent polyaspartamide protein linkers will greatly assist efforts to analyze and regulate the cellular adhesion to and phenotypic activities of a wide array of substrates and devices. PMID- 22053984 TI - Ordered carbon nanotubes for optical power limiting devices. AB - The electrospinning (ES) process was used to fabricate composite nanofibers (NFs) of poly(methyl methacrylate), PMMA, with embedded multiwalled carbon nanotubes (MWNTs) from a solution of PMMA in N,N-dimethylformamide (DMF) with homogenously dispersed MWNTs. Using both the sinklike and the elongation flows in the electrospinning process, we aligned the carbon nanotubes (CNTs) along the fiber axis. The NFs were subsequently deposited in an aligned manner on a glass surface using the electrostatic lens created by the edge of a rotating wheel collector. Semitransparent optical power limiter (OPL) films (~50% transmittance) were fabricated using an optically compatible polymeric resin infiltrated into the collected NFs. These comprised oriented NFs with different carbon nanotube loadings and film thicknesses. The OPLs exhibited high limiting abilities, with a limiting threshold of 1.5 J/cm(2) at about 50% linear transmittance. Some degree of polarization was also achieved, but significantly lower than expected because of the NF orientation. PMID- 22053985 TI - Loss of interferon regulatory factor 5 (IRF5) expression in human ductal carcinoma correlates with disease stage and contributes to metastasis. AB - INTRODUCTION: New signaling pathways of the interleukin (IL) family, interferons (IFN) and interferon regulatory factors (IRF) have recently been found within tumor microenvironments and in metastatic sites. Some of these cytokines stimulate while others inhibit breast cancer proliferation and/or invasion. IRFs, a family of nine mammalian transcription factors, have multiple biologic functions that when dysregulated may contribute to tumorigenesis; most well-known are their roles in regulating/initiating host immunity. Some IRF family members have been implicated in tumorigenesis yet little is still known of their expression in primary human tumors or their role(s) in disease development/progression. IRF5 is one of the newer family members to be studied and has been shown to be a critical mediator of host immunity and the cellular response to DNA damage. Here, we examined the expression of IRF5 in primary breast tissue and determined how loss of expression may contribute to breast cancer development and/or progression. METHODS: Formalin-fixed paraffin-embedded archival breast tissue specimens from patients with atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were examined for their expression of IRF1 and IRF5. Knockdown or overexpression of IRF5 in MCF-10A, MCF-7 and MDA-MB-231 mammary epithelial cell lines was used to examine the role of IRF5 in growth inhibition, invasion and tumorigenesis. RESULTS: Analysis of IRF expression in human breast tissues revealed the unique down-regulation of IRF5 in patients with different grades of DCIS and IDC as compared to IRF1; loss of IRF5 preceded that of IRF1 and correlated with increased invasiveness. Overexpression of IRF5 in breast cancer cells inhibited in vitro and in vivo cell growth and sensitized them to DNA damage. Complementary experiments with IRF5 siRNAs made normal mammary epithelial cells resistant to DNA damage. By 3-D culture, IRF5 overexpression reverted MDA-MB-231 to normal acini-like structures; cells overexpressing IRF5 had decreased CXCR4 expression and were insensitive to SDF-1/CXCL12-induced migration. These findings were confirmed by CXCR4 promoter reporter assays. CONCLUSIONS: IRF5 is an important tumor suppressor that regulates multiple cellular processes involved in the conversion of normal mammary epithelial cells to tumor epithelial cells with metastatic potential. PMID- 22053986 TI - Noncovalent organocatalysis: a powerful tool for the nucleophilic epoxidation of alpha-ylideneoxindoles. AB - A novel asymmetric nucleophilic epoxidation for alpha-ylideneoxindole esters has been successfully devised, resulting in enantioenriched spiro compounds with two new contiguous stereocenters. The employed (S)-alpha,alpha-diphenylprolinol functions as a bifunctional catalyst, creating a complex H-bond network in conjunction with a substrate and an oxidant. PMID- 22053987 TI - Characterization of the Mycobacterium tuberculosis proteome by liquid chromatography mass spectrometry-based proteomics techniques: a comprehensive resource for tuberculosis research. AB - Approximately, one-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. Secreted and membrane proteins that interact with the host play important roles for the pathogenicity of the bacteria and are potential drug targets or components of vaccines. In this present study, subcellular fractionation in combination with membrane enrichment was used to comprehensively analyze the M. tuberculosis proteome. The proteome of the M. tuberculosis cell wall, membrane, cytosol, lysate, and culture filtrate was defined with a high coverage. Exceptional enrichment for membrane proteins was achieved using wheat germ agglutinin (WGA)-affinity two-phase partitioning, a technique that has to date not yet been exploited for the enrichment of mycobacterial membranes. Overall, 1051 M. tuberculosis protein groups including 183 transmembrane proteins have been identified by LC-MS/MS analysis using stringent database search criteria with a minimum of two peptides and an estimated FDR of less than 1%. With many mycobacterial antigens and lipoglycoproteins identified, the results from this study suggest that many of the newly discovered proteins could represent potential candidates mediating host pathogen interactions. In addition, this data set provides experimental information about protein localization and thus serves as a valuable resource for M. tuberculosis proteome research. PMID- 22053988 TI - Sociodemographic and geographic characteristics associated with patient visits to osteopathic physicians for primary care. AB - BACKGROUND: Health care reform promises to dramatically increase the number of Americans covered by health insurance. Osteopathic physicians (DOs) are recognized for primary care, including a "hands-on" style with an emphasis on patient-centered care. Thus, DOs may be well positioned to deliver primary care in this emerging health care environment. METHODS: We used data from the National Ambulatory Medical Care Survey (2002-2006) to study sociodemographic and geographic characteristics associated with patient visits to DOs for primary care. Descriptive analyses were initially performed to derive national population estimates (NPEs) for overall patient visits, primary care patient visits, and patient visits according to specialty status. Osteopathic and allopathic physician (MD) patient visits were compared using cross-tabulations and multiple logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) for DO patient visits. The latter analyses were also conducted separately for each geographic characteristic to assess the potential for effect modification based on these factors. RESULTS: Overall, 134,369 ambulatory medical care visits were surveyed, representing 4.6 billion (NPE) +/- 220 million (SE) patient visits when patient visit weights were applied. Osteopathic physicians provided 336 million +/- 30 million (7%) of these patient visits. Osteopathic physicians provided 217 million +/- 21 million (10%) patient visits for primary care services; including 180 million +/- 17 million (12%) primary care visits for adults (21 years of age or older) and 37 million +/- 5 million (5%) primary care visits for minors. Osteopathic physicians were more likely than MDs to provide primary care visits in family and general medicine (OR, 6.03; 95% CI, 4.67-7.78), but were less likely to provide visits in internal medicine (OR, 0.37; 95% CI, 0.24-0.58) or pediatrics (OR, 0.21; 95% CI, 0.11-0.40). Overall, patients in the pediatric and geriatric ages, Blacks, Hispanics, and persons in the South and West were less likely to utilize DOs, although there was some evidence of effect modification according to United States Census region. CONCLUSIONS: Health care reform provides unprecedented opportunities for DOs to reach historically underserved populations and to overcome the "pediatric primary-care paradox." PMID- 22053989 TI - Pressure-induced order transition in nanodot-forming diblock copolymers at the air/water interface. AB - Understanding and controlling the processes in block copolymer (BC) monolayers at the air/water interface during surface area compression is a key issue for producing ultrathin films of predetermined morphology with well-defined order and known dimensions. Langmuir isotherms of nanodot-forming BC monolayers generally display a plateau indicative of a 2D phase transition, which has been the subject of various interpretations in the literature. Here, based on investigations of Langmuir-Blodgett and Langmuir-Schaefer nanodot films of PS-P4VP mixed with 3-n pentadecylphenol (PDP), we show by atomic force microscopy (AFM) that it involves a change in nanodot packing order (from quasi-hexagonal to quasi-square), argued to be a general phenomenon for nanodot BC monolayers. It is accompanied by system specific conformational changes (as discussed in previous literature), which, in the present case, implicate PDP alkyl chain ordering, as deduced previously from in situ infrared data and indirectly supported here by AFM imaging. PMID- 22053991 TI - Osseointegration of porous titanium implants with and without electrochemically deposited DCPD coating in an ovine model. AB - BACKGROUND: Uncemented fixation of components in joint arthroplasty is achieved primarily through de novo bone formation at the bone-implant interface and establishment of a biological and mechanical interlock. In order to enhance bone implant integration osteoconductive coatings and the methods of application thereof are continuously being developed and applied to highly porous and roughened implant substrates. In this study the effects of an electrochemically deposited dicalcium phosphate dihydrate (DCPD) coating of a porous substrate on implant osseointegration was assessed using a standard uncemented implant fixation model in sheep. METHODS: Plasma sprayed titanium implants with and without a DCPD coating were inserted into defects drilled into the cancellous and cortical sites of the femur and tibia. Cancellous implants were inserted in a press-fit scenario whilst cortical implants were inserted in a line-to-line fit. Specimens were retrieved at 1, 2, 4, 8 and 12 weeks postoperatively. Interfacial shear-strength of the cortical sites was assessed using a push-out test, whilst bone ingrowth, ongrowth and remodelling were investigated using histologic and histomorphometric endpoints. RESULTS: DCPD coating significantly improved cancellous bone ingrowth at 4 weeks but had no significant effect on mechanical stability in cortical bone up to 12 weeks postoperatively. Whilst a significant reduction in cancellous bone ongrowth was observed from 4 to 12 weeks for the DCPD coating, no other statistically significant differences in ongrowth or ingrowth in either the cancellous or cortical sites were observed between TiPS and DCPD groups. CONCLUSION: The application of a DCPD coating to porous titanium substrates may improve the extent of cancellous bone ingrowth in the early postoperative phase following uncemented arthroplasty. PMID- 22053992 TI - Effects of low-level laser therapy at wavelengths of 660 and 808 nm in experimental model of osteoarthritis. AB - The aim of the present study was to analyze the influence of low-level laser radiation at wavelengths of 660 and 808 nm in an experimental model of osteoarthritis (OA). The sample was composed of 36 male adult Wistar rats divided into three groups (G1, G2 and G3). For the induction of cartilage injury, three injections of 4% papain and 10 MUL of a cysteine solution were performed at right knee of the hind leg. Two weeks after the last injection, group G1 was treated with InGaAlP (660 nm, 100 mW, 3.57 W cm(-2), 40 s) and G2 was treated with AsGaAl (808 nm, 100 mW, 3.57 W cm(-2), 40 s) both with energy of 4 J. There were significant differences in the type of squamous epithelium between days 7 and 14 in G2 (P < 0.05) and on day 14 between G1 and G2 (P < 0.05). Moreover, statistically significant differences were found in the formation of new blood vessels between G1 and G3 on days 7 and 21 as well as between G2 and G3 on day 21. The formation of fibrotic tissue was greater in G3 (P < 0.05). In conclusion, laser therapy, especially at a wavelength of 808 nm, stimulated angiogenesis and reduced the formation of fibrosis in an experimental model of OA. PMID- 22053993 TI - One proposal to solve the organ shortage crisis in full understanding of donor transmitted malignancies in kidney transplantation. PMID- 22053994 TI - The ocular complications of mustard gas poisoning and their association with the respiratory system involvement: an experience in 112 Iranian veterans. AB - OBJECTIVE: To investigate ocular complications and their association with respiratory involvement in 112 patients with first exposure of mustard gas for at least 19 years ago. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred and twelve veterans (224 eyes) with documented exposure to sulphur mustard (SM) for the first time. METHODS: All participants were interviewed and clinically examined by an ophthalmologist and a specialist in respiratory disease. Data filed from the exposure time and regular follow-ups thereafter were reviewed. The patients were categorized in three subgroups according to the severity of respiratory system involvement as determined by spirometry (normal, mild, and moderate-severe). RESULTS: Subjective and objective ocular problems were documented in 83.9 and 70.6% of victims, respectively. Normal, mild, and moderate severe respiratory system problems were present in 37.5, 22.3 and 40.2% of cases, respectively. Abnormal ocular findings were severe conjunctival vascular tortuosity (65.2%, mean: 13.71 years after exposure), corneal neovascularization (19.6%, mean: 16.54 years after exposure), conjunctival/limbal vessels with ampulliform dilatation (17.9%, mean: 9.33 years after exposure), and delayed keratitis (9.8%, mean: 19.54 years after exposure). The ocular abnormal findings were significantly more frequent in victims with moderate-severe respiratory system involvement. CONCLUSION: Structural ocular abnormalities are frequently found in patients with long-term history of mustard gas intoxication. These abnormalities are more common in severe respiratory system involvement. PMID- 22053995 TI - Polymers containing hydroxamate groups: nanoreactors for hydrolysis of phosphoryl esters. AB - A polyhydroxamicalkanoate (PHA) polymer containing the functional groups hydroxamic acid and carboxylic acid with the ability to accelerate dephosphorylation reactions is proposed. The methodology used to prepare this polymer favored the position of the two functional groups next to each other, which allows for the cooperativity between these groups. This cooperative effect has an important role when one wants to mimic enzymes. The catalytic effect promoted by the polymer was evaluated on the cleavage of the bis(2,4 dinitrophenyl) phosphate (BDNPP) and diethyl 2,4-dinitrophenyl phosphate (DEDNPP) esters. Indeed, PHA was very efficient and promiscuous because it increased the rate of both reactions by a factor of up to 10(6)-fold. Isothermal titration calorimetry (ITC) experiments showed that the presence of PHA aids the formation of cetyltrimethylammonium bromide (CTABr) micelles. Thus, the effect of the cationic surfactant CTABr on the dephosphorylation of BDNPP by PHA was also investigated, and it was observed that, when CTABr is added to PHA, the reaction is ca. 15-fold faster compared to the reaction when only PHA is present. PMID- 22053996 TI - Random sperm use and genetic effects on worker caste fate in Atta colombica leaf cutting ants. AB - Sperm competition can produce fascinating adaptations with far-reaching evolutionary consequences. Social taxa make particularly interesting models, because the outcome of sexual selection determines the genetic composition of groups, with attendant sociobiological consequences. Here, we use molecular tools to uncover some of the mechanisms and consequences of sperm competition in the leaf-cutting ant Atta colombica, a species with extreme worker size polymorphism. Competitive PCR allowed quantification of the relative numbers of sperm stored by queens from different males, and offspring genotyping revealed how sperm number translated into paternity of eggs and adult workers. We demonstrate that fertilization success is directly related to sperm numbers, that stored sperm are well-mixed and that egg paternity is constant over time. Moreover, worker size was found to have a considerable genetic component, despite expectations that genetic effects on caste fate should be minor in species with a low degree of polyandry. Our data suggest that sexual conflict over paternity is largely resolved by the lifetime commitment between mates generated by long-term sperm storage, and show that genetic variation for caste can persist in societies with comparatively high relatedness. PMID- 22053998 TI - Prof. Dr. J. G. van Bekkum's Farewell. PMID- 22053999 TI - Foot-and-mouth disease vaccine production and research in the Netherlands. AB - Summary The paper reviews developments in foot-and-mouth disease research with an emphasis on the Netherlands and research developments at the Central Veterinary Institute. PMID- 22054000 TI - Maedi-visna control in sheep III: Results and evaluation of a voluntary control program in the Netherlands over a period of four years. AB - Summary The results of the first four years of the Dutch national voluntary maedi-visna control program, which was launched on January 1, 1982, are presented. At the end of the observation period, 1711 breeding flocks representing 70% of the registered breeding flocks participated. The program is based on accreditation of flocks that have passed two successive serological tests with an interval of six months between and post-accreditation tests every 12 months. The flocks have to conform to a set of specific regulations. Sheep sold from such flocks receive a certificate stating that their origin was accredited. A total of 1212 flocks gained accredition. Of these flocks, 29.5% were free from infection from the beginning, 35.6% were created by total replacement of the original stock, 19.6% employed repeated testing and culling of positives, and 15.3% were created by artificial rearing of colostrum-deprived lambs. A total of 22 flocks lost accreditation due to detection of 36 seropositives. These positives and their progeny were culled, and all flocks regained accreditation after passing the two negative flock tests required. In a total of seven flocks, an unusual course of events during the pre-accreditation stage was observed; this was mainly attributed to late seroconversions and uncommon degrees of horizontal transmission. The results indicate that this certification yields a substantial guarantee of freedom from maedi-visna virus and they indirectly show that the basic design of the program has been adequate. PMID- 22054001 TI - Vaccines against Aujeszky's disease: Comparison of efficacy, DNA fingerprints and antibody response to glycoprotein I. AB - Summary The efficacy of two inactivated and three attenuated Aujeszky's disease virus (ADV) vaccines was compared in pigs in a standardised test. After vaccination, excretion of attenuated vaccine viruses was not detected. All vaccines were capable of preventing mortality, but none conferred complete protection against challenge with a virulent strain of ADV 3 months after the first vaccination. After a single vaccination, no large differences in vaccine efficacy were observed. Revaccination markedly enhanced protection; however, with one vaccine this was not the case. The two inactivated vaccines induced quite different levels of neutralizing antibodies. Two vaccine viruses had a wild type DNA fingerprint and gave rise to an antibody response to glycoprotein I (gI) of ADV. The three remaining vaccines carried a deletion in the unique short region of the genome. Two of them failed to induce gI-antibody in pigs. Pigs given the third 'deleted' vaccine did not respond uniformly to gI. With regard to control of Aujeszky's disease, efficacious vaccines with a 'serological' marker may be preferred in the future. PMID- 22054002 TI - Epizootiology of swine fever. AB - Summary In countries with an intensive pig production system, swine fever (SF), where present, may be regarded as one of the economically most important pig diseases. Although reservoirs of virus and pathways of transmission are well understood, field experience has shown that the disease is extremely difficult to eradicate, especially in countries with intensive pig breeding. The virulence of the strains circulating in the field and the measures applied to control the disease determine to a large extent the course of an epizootic. Outbreaks of highly virulent strains are readily recognised. Epizootics caused by low virulent strains are characterised by indistinct signs of disease, slow spread of virus through the herd and the comparatively important role of the 'carrier sow syndrome'. The latter phenomenon may result in the birth of healthy looking but persistently infected and immune-tolerant piglets. This and the occurrence of chronic infections are largely responsible for the perpetuation of the virus in the pig population. The 1982-1985 epizootic of SF in the Netherlands showed an almost equal prevalence of outbreaks in breeding and fattening herds. In proportion to the number of herds in the country, there was in both categories an approximately linear relationship between the risk of infection and the size of the herds. The proportion of affected breeding herds increased as mass vaccination of areas at risk was started earlier in the epizootic. In close knit communities with large breeding units, man should be regarded as the single most important factor in the herd-to-herd transmission of the virus, whereas in fattening units and in areas with small pig farms, transport and introduction of infected pigs into herds accounts for the majority of outbreaks and for the spread of the disease. Farms visited by persons handling pigs subsequent to contact with an infected herd should, therefore, be included in the epizootiological investigations. Virological and serological methods are indispensable in order to confirm or to rule out the possibility of infection of suspected contacts, especially in outbreaks caused by strains of low virulence. Continuous education of farmers regarding the importance of maintaining precautionary measures against the introduction of contagious diseases and, in the case of an advancing epizootic, special instructions to all people entering piggeries, would contribute greatly to reducing the untraceable pathways of SF spread. PMID- 22054004 TI - Erratum. PMID- 22054006 TI - Oligomerization oscillations of L-lactic acid in solution. AB - We employ high-performance liquid chromatography with diode array, evaporative light scattering, and mass spectrometric detection to monitor the oligomerization of L-lactic acid in pure acetonitrile and in 70% aqueous ethanol. The production of higher oligomers appears to proceed in an oscillatory fashion. A model is presented that involves the formation of aggregates (micelles), which catalyze the oligomerization. PMID- 22053997 TI - Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2. AB - INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. RESULTS: The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 * 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. CONCLUSIONS: The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers. PMID- 22054008 TI - Oral delivery of the appetite suppressing peptide hPYY(3-36) through the vitamin B12 uptake pathway. AB - hPYY(3-36) injections have shown positive effects on appetite regulations, sparking increased interest in hPYY(3-36) research. Of great interest is oral delivery of hPYY(3-36) that can achieve clinically relevant weight-loss outcomes in what would be a highly patient compliant route. Successful oral delivery of other peptides utilizing the vitamin B12 pathway has been shown but below clinically relevant levels. Herein, we present clinically relevant in vivo oral delivery of B12-hPYY(3-36) conjugates. PMID- 22054007 TI - An update on direct genotoxicity as a molecular mechanism of ochratoxin a carcinogenicity. AB - Ochratoxin A (OTA) is a naturally occurring chlorophenolic fungal toxin that contaminates a wide range of food products and poses a cancer threat to humans. The mechanism of action (MOA) for OTA renal carcinogenicity is a controversial issue. In 2005, direct genotoxicity (covalent DNA adduct formation) was proposed as a MOA for OTA-mediated carcinogenicity [ Manderville , R. A. ( 2005 ) Chem. Res. Toxicol. 18 , 1091 - 1097 ]. At that time, inconsistent results had been published on OTA genotoxicity/mutagenicity, and conclusive evidence for OTA-mediated DNA adduction had been lacking. In this update, published data from the past 6-7 years are presented that provide new hypotheses for the MOA of OTA mediated carcinogenicity. While direct genotoxicity remains a controversial issue for OTA, new findings from the Umemura and Nohmi laboratories provide definitive results for the mutagenicity of OTA in the target tissue (outer medulla) of male rat kidney that rules out oxidative DNA damage. These findings, coupled with our own efforts that provide new structural evidence for DNA adduction by OTA, has strengthened the argument for involvement of direct genotoxicity in OTA-mediated renal carcinogenesis. This MOA should be taken into consideration for OTA human risk assessment. PMID- 22054009 TI - Engineering cell surfaces via liposome fusion. AB - In this study, we have rewired cell surfaces with ketone and oxyamine molecules based on liposome fusion for applications in cell-surface engineering. Lipid vesicles, functionalized with ketone and oxyamine molecules, display complementary chemistry and undergo recognition, docking, and subsequent fusion upon covalent oxime bond formation. Liposome fusion was characterized by several techniques including matrix-assisted laser-desorption/ionization mass spectrometry (MALDI-MS), light scattering, fluorescence resonance energy transfer (FRET), and transmission electron microscopy (TEM). When cultured with cells, ketone- and oxyamine-containing liposomes undergo spontaneous membrane fusion to present the respective molecules from cell surfaces. Ketone-functionalized cell surfaces serve as sites for chemoselective ligation with oxyamine-conjugated molecules. We tailored and fluorescently labeled cell surfaces with an oxyamine conjugated rhodamine dye. As an application of this cell-surface engineering strategy, ketone- and oxyamine-functionalized cells were patterned on oxyamine- and ketone-presenting surfaces, respectively. Cells adhered, spread, and proliferated in the patterned regions via interfacial oxime linkage. The number of ketone molecules on the cell surface was also quantified by flow cytometry. PMID- 22054010 TI - The use of ginger (Zingiber officinale) for the treatment of pain: a systematic review of clinical trials. AB - BACKGROUND: Zingiber officinale (Z. officinale), commonly known as ginger, has been widely used traditionally for a variety of medicinal purposes, one of which is for the treatment of pain. The aim of this systematic review was to evaluate the evidence from all human participant clinical trials that have assessed the efficacy of ginger for the treatment of any type of pain. METHODS: Following a protocol, multiple databases were sought using comprehensive search strategies for Z. officinale and pain together with a trial filter for randomized or controlled clinical trials. Trials testing the efficacy of Z. officinale, used as a sole oral treatment against a comparison condition in human adults suffering from any pain condition, were included. RESULTS: Seven published articles, reporting a total of eight trials (481 participants), were included in the review. Six trials (two for osteoarthritis, one for dysmenorrhea, and three for experimentally induced acute muscle pain) found that the use of Z. officinale reduced subjective pain reports. The methodological quality of the included articles was variable. When assessed using the Jadad scale, which allows a score of between 0 and 5 to be given, included articles obtained Jadad ratings ranging from 2 to 5. CONCLUSION: Due to a paucity of well-conducted trials, evidence of the efficacy of Z. officinale to treat pain remains insufficient. However, the available data provide tentative support for the anti-inflammatory role of Z. officinale constituents, which may reduce the subjective experience of pain in some conditions such as osteoarthritis. Further rigorous trials therefore seem to be warranted. PMID- 22054011 TI - Hand preference in children with an idiopathic toe walking gait. PMID- 22054013 TI - General approach to allenes through copper-catalyzed gamma-selective and stereospecific coupling between propargylic phosphates and alkylboranes. AB - Copper-catalyzed gamma-selective coupling between propargylic phosphates and alkylboron compounds (alkyl-9-BBN, prepared by hydroboration of alkenes with 9 BBN-H) affords multisubstituted allenes with various functional groups. The reaction of enantioenriched propargylic phosphates to give axially chiral allenes proceeds with excellent point-to-axial chirality transfer with 1,3-anti stereochemistry. PMID- 22054012 TI - Aldose reductase deficiency in mice protects from ragweed pollen extract (RWE) induced allergic asthma. AB - BACKGROUND: Childhood hospitalization related to asthma remains at historically high levels, and its incidence is on the rise world-wide. Previously, we have demonstrated that aldose reductase (AR), a regulatory enzyme of polyol pathway, is a major mediator of allergen-induced asthma pathogenesis in mouse models. Here, using AR null (AR-/-) mice we have investigated the effect of AR deficiency on the pathogenesis of ragweed pollen extract (RWE)-induced allergic asthma in mice and also examined the efficacy of enteral administration of highly specific AR inhibitor, fidarestat. METHODS: The wild type (WT) and AR-/- mice were sensitized and challenged with RWE to induce allergic asthma. AR inhibitor, fidarestat was administered orally. Airway hyper-responsiveness was measured in unrestrained animals using whole body plethysmography. Mucin levels and Th2 cytokine in broncho-alveolar lavage (BAL) were determined using mouse anti Muc5A/C ELISA kit and multiplex cytokine array, respectively. Eosinophils infiltration and goblet cells were assessed by H&E and periodic acid Schiff (PAS) staining of formalin-fixed, paraffin-embedded lung sections. T regulatory cells were assessed in spleen derived CD4+CD25+ T cells population. RESULTS: Deficiency of AR in mice led to significantly decreased PENH, a marker of airway hyper responsiveness, metaplasia of airway epithelial cells and mucus hyper-secretion following RWE-challenge. This was accompanied by a dramatic decrease in infiltration of eosinophils into sub-epithelium of lung as well as in BAL and release of Th2 cytokines in response to RWE-challenge of AR-/- mice. Further, enteral administration of fidarestat significantly prevented eosinophils infiltration, airway hyper-responsiveness and also markedly increased population of T regulatory (CD4+CD25+FoxP3+) cells as compared to RWE-sensitized and challenged mice not treated with fidarestat. CONCLUSION: Our results using AR-/- mice strongly suggest the role of AR in allergic asthma pathogenesis and effectiveness of oral administration of AR inhibitor in RWE-induced asthma in mice supports the use of AR inhibitors in the treatment of allergic asthma. PMID- 22054014 TI - Inhibition of type I interferon production via suppressing IKK-gamma expression: a new strategy for counteracting host antiviral defense by influenza A viruses? AB - Blockage of the induction of type I interferons (IFNs) is essential for the success of influenza virus proliferation in host cells. Several molecular mechanisms by which influenza viruses inhibit IFN induction have been characterized. Here we report a potentially new strategy influenza viruses employ to inhibit IFN production during viral infection. Through a two-dimensional gel electrophoresis based proteomic approach, we found that the expression of IkappaB kinase-gamma (IKKgamma) was suppressed by influenza A virus infection in human lung epithelial A549 cells. Silencing of cellular IKKgamma by small interfering RNA led to enhanced replication of influenza viruses. Concomitantly, overexpression of IKKgamma resulted in increased production of IFNalpha/beta, whereas influenza virus infection completely eliminated the IKKgamma overexpression-induced production of IFNalpha/beta. Our results suggest that IKKgamma and influenza virus are mutually inhibitory, and influenza viruses may inhibit IFN production through suppressing the expression of IKKgamma during viral infection. PMID- 22054015 TI - Does the presence of one feature of borderline personality disorder have clinical significance? Implications for dimensional ratings of personality disorders. AB - OBJECTIVE: In the draft proposal for DSM-5, the Work Group for Personality and Personality Disorders recommended that dimensional ratings of personality disorders replace DSM-IV's categorical approach toward classification. If a dimensional rating of personality disorder pathology is to be adopted, then the clinical significance of minimal levels of pathology should be established before they are formally incorporated into the diagnostic system because of the potential unforeseen consequences of such ratings. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the low end of the severity dimension and compared psychiatric outpatients with 0 or 1 DSM-IV criterion for borderline personality disorder on various indices of psychosocial morbidity. METHOD: Three thousand two hundred psychiatric outpatients were evaluated with semistructured diagnostic interviews for DSM-IV Axis I and Axis II disorders. The present report is based on the 1,976 patients meeting 0 or 1 DSM-IV criterion for borderline personality disorder. RESULTS: The reliability of determining if a patient was rated with 0 or 1 criterion for borderline personality disorder was good (kappa = 0.70). Compared to patients with 0 borderline personality disorder criteria, patients with 1 criterion had significantly more current Axis I disorders (P < .001), suicide attempts (P < .01), suicidal ideation at the time of the evaluation (P < .001), psychiatric hospitalizations (P < .001), and time missed from work due to psychiatric illness (P < .001) and lower ratings on the Global Assessment of Functioning (P < .001). CONCLUSIONS: Low-severity levels of borderline personality disorder pathology, defined as the presence of 1 criterion, can be determined reliably and have validity. PMID- 22054016 TI - Modelling ultrasound-induced mild hyperthermia of hyperplasia in vascular grafts. AB - BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) vascular grafts frequently develop occlusive neointimal hyperplasia as a result of myofibroblast over growth, leading to graft failure. ePTFE exhibits higher ultrasound attenuation than native soft tissues. We modelled the selective absorption of ultrasound by ePTFE, and explored the feasibility of preventing hyperplasia in ePTFE grafts by ultrasound heating. Specifically, we simulated the temperature profiles of implanted grafts and nearby soft tissues and blood under ultrasound exposure. The goal was to determine whether ultrasound exposure of an ePTFE graft can generate temperatures sufficient to prevent cell growth on the graft without damaging nearby soft tissues and blood. METHODS: Ultrasound beams from two transducers (1.5 and 3.2 MHz) were simulated in two graft/tissue models, with and without an intra-graft cellular layer mimicking hyperplasia, using the finite-difference time-domain (FDTD) method. The resulting power deposition patterns were used as a heat source for the Pennes bioheat equation in a COMSOL((r)) Multiphysics heat transfer model. 50 degrees C is known to cause cell death and therefore the transducer powers were adjusted to produce a 13 degrees C temperature rise from 37 degrees C in the ePTFE. RESULTS: Simulations showed that both the frequency of the transducers and the presence of hyperplasia significantly affect the power deposition patterns and subsequent temperature profiles on the grafts and nearby tissues. While neither transducer significantly raised the temperature of the blood, the 1.5-MHz transducer was less focused and heated larger volumes of the graft and nearby soft tissues than the 3.2-MHz transducer. The presence of hyperplasia had little effect on the blood's temperature, but further increased the temperature of the graft and nearby soft tissues in response to either transducer. Skin cooling and blood flow play a significant role in preventing overheating of the native tissues. CONCLUSIONS: Modelling shows that ultrasound can selectively heat ePTFE grafts and produce temperatures that cause cell death on the graft. The temperature increase in blood is negligible and that in the adjacent soft tissues may be minimized by skin cooling and using appropriate transducers. Therefore, ultrasound heating may have the potential to reduce neointimal hyperplasia and failure of ePTFE vascular grafts. PMID- 22054017 TI - Effectiveness of Motivational Interviewing in improving lipid level in patients with dyslipidemia assisted by general practitioners: Dislip-EM study protocol. AB - BACKGROUND: The non-pharmacological approach to cholesterol control in patients with hyperlipidemia is based on the promotion of a healthy diet and physical activity. Thus, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns, and that include brief advice and counseling services. Within this context, Motivational Interviewing has proven to be effective in changing health behaviors in specific cases. However, more robust evidence is needed on the effectiveness of Motivational Interviewing in treating chronic pathologies -such as dyslipidemia- in patients assisted by general practitioners. This article describes a protocol to assess the effectiveness of MI as compared with general practice (brief advice), with the aim of improving lipid level control in patients with dyslipidemia assisted by a general practitioner. METHODS/DESIGN: An open, two-arm parallel, multicentre, cluster, controlled, randomized, clinical trial will be performed. A total of 48-50 general practitioners from 35 public primary care centers in Spain will be randomized and will recruit 436 patients with dyslipidemia. They will perform an intervention based either on Motivational Interviewing or on the usual brief advice. After an initial assessment, follow ups will be performed at 2, 4, 8 and 12 months. Primary outcomes are lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and cardiovascular risk. The study will assess the degree of dietary and physical activity improvement, weight loss in overweight patients, and adherence to treatment guidelines. DISCUSSION: Motivational interview skills constitute the primary strategies GPs use to treat their patients. Having economical, simple, effective and applicable techniques is essential for primary care professionals to help their patients change their lifestyle and improve their health. This study will provide scientific evidence on the effectiveness of Motivational interviewing, and will be performed under strict control over the data collected, ensuring the maintenance of therapeutic integrity. TRIALS REGISTRATION: ClinicalTrials.gov (NCT01282190). PMID- 22054018 TI - Diagnosis and management of an immature teratoma during ovarian stimulation: a case report. AB - INTRODUCTION: The discovery of a mature teratoma (dermoid cyst) of the ovary during ovarian stimulation is not a rare event. Conversely, we could not find any reported cases of immature teratoma in such a situation. Clinical and ultrasound arguments for this immature form are scarcely or poorly evaluated. CASE PRESENTATION: We describe the case of a 31-year-old Caucasian woman with primary infertility, who developed an immature teratoma during an in vitro fertilization ovarian stimulation cycle. CONCLUSIONS: Ultrasound signs of an atypical cyst during ovarian stimulation allowed us to adopt a careful medical attitude and to adapt the required surgical oncological treatment. PMID- 22054020 TI - Age-related changes in the expression of NMDA, serotonin, and GAD in the central auditory system of the rat. AB - CONCLUSIONS: We suggest that age-induced changes of serotonin, N-methyl-d aspartate receptor (NMDAR), and glutamate decarboxylase (GAD) expression in rats are dependent on the specific location in the central auditory system (CAS). OBJECTIVES: Despite the importance of understanding changes in neurotransmitters during presbycusis, only a few studies have assessed age-associated changes in neurotransmitter at each level of the CAS. We therefore evaluated effects of aging on neurotransmission in the CAS of rats. METHODS: The concentrations of serotonin, NMDAR, and GAD were assayed immunohistochemically in the cochlear nucleus (CN), superior olivary nucleus (SON), inferior colliculus (IC), medial geniculate body (MGB), and auditory cortex (AC) of Sprague-Dawley rats, aged 2 weeks (n = 20) or 24 months (n = 20). RESULTS: The total number of neuronal cell bodies of the CAS did not differ significantly at each level between young and aged rats (p > 0.05). Serotonin expression was increased with age in the IC and MGB, but decreased in the CN, SON, and AC (p < 0.05). NMDAR was significantly higher in the CN, MGB, and AC of aged compared with young rats, but was significantly decreased over time in the SOC and IC (p < 0.05). GAD67 was increased with age in the MGB and AC and decreased in the CN and SON (p < 0.05), but was not changed in the IC. PMID- 22054019 TI - Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis. AB - BACKGROUND: Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition. METHODS: This study was designed to examine the effect of long-acting calcium channel blocker (CCB), Azelnidipine (AZL) on contractile dysfunction, intracellular calcium (Ca2+) cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP) injection of streptozotocin (STZ). Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-relengthening (TR90), maximal velocity of shortening/relengthening (+/- dL/dt) and intracellular Ca2+ fluorescence. RESULTS: Diabetic heart showed significantly depressed PS, +/- dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD), calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment. CONCLUSION: Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property. PMID- 22054021 TI - Analysis of the molecular interactions and complexation of chloroquine with bovine serum albumin. AB - BACKGROUND: Pharmacokinetic parameters, drug bioavailability, and biological activities depend on the mechanisms of interaction with serum albumin. In this study, the binding properties as well as mechanisms of interaction of chloroquine with bovine serum albumin (BSA) were investigated. METHODS: The binding of chloroquine with BSA was carried out using a microcalorimetric approach. The mechanism of binding, the number of binding molecules as well as changes of BSA upon complexation with chloroquine were investigated. RESULTS: The binding isotherms indicated a variable number of binding sites of chloroquine on one molecule of BSA. At lower temperatures, larger numbers of binding sites were available for chloroquine, these decrease by increasing the temperature. The binding constant of chloroquine with BSA varied from 9.4*103 M-1 at 25 degrees C to 5.7*103 M-1 at 40 degrees C. Chloroquine showed temperature-dependent binding affinity, with stronger affinity at lower temperature. By increasing the temperature, from 25 degrees C to 40 degrees C, the binding affinity was decreased by approximately 60% of its value. CONCLUSIONS: Chloroquine showed weak binding affinity with BSA. The weak binding affinity of chloroquine with BSA is important in determining the drug-drug interactions at the binding sites of BSA. The presence of stronger binding ligands, e.g., chloramphenicol, tetracyclines or diclofenac, can compete with chloroquine for its binding sites, and therefore lowers its serum albumin binding. This study will be helpful in understanding the binding properties of mechanisms of interaction of chloroquine with BSA. PMID- 22054022 TI - Efficient emulsification of viscous oils at high drop volume fraction. AB - It is shown experimentally in this study that the increase of drop volume fraction can be used as an efficient tool for emulsification of viscous oils in turbulent flow. In a systematic series of experiments, the effects of drop volume fraction and viscosity of the dispersed phase on the mean, d(32), and maximum, d(V95), diameters of the drops, formed during emulsification, are quantified. The volume fraction, Phi, of the dispersed oily phase is varied between 1% and 90%, and oils with viscosity varying between 3 and 10,000 mPa.s are studied. All experiments are performed at sufficiently high surfactant concentration, as to avoid possible drop-drop coalescence during emulsification. The analysis of the experimental data shows that there is a threshold drop volume fraction, Phi(TR), at which a transition from inertial turbulent regime into viscous turbulent regime of emulsification occurs, due to the increased overall viscosity of the emulsion. At Phi < Phi(TR), d(32) and d(V95) depend weakly on Phi and are well described by known theoretical expression for emulsification in inertial turbulent regime (Davies, Chem. Eng. Sci. 1985, 40, 839), which accounts for the effects of oil viscosity and interfacial tension. At Phi > Phi(TR), both d(32) and polydispersity of the formed emulsions decrease very significantly with the increase of Phi (for the oils with eta(D) > 10 mPa.s). Thus, very efficient emulsification of the viscous oils is realized. Very surprisingly, a third regime of emulsification is observed in the range of concentrated emulsions with Phi > 75%, where the mean drop size and emulsion polydispersity are found experimentally to be very similar for all oils and surfactants studied-an experimental fact that does not comply with any of the existing models of drop breakup during emulsification. Possible mechanistic explanations of this result are discussed. The experimental data for semiconcentrated and concentrated emulsions with Phi > Phi(TR) are described by a simple scaling expression, which accounts for the effects of all main factors studied. PMID- 22054024 TI - When good intentions are not enough: obtaining follow-up data in living kidney donors. AB - The Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/UNOS) has increased the amount of data collected before and after donation and increased the duration of donor follow-up to 2 years, yet there is evidence that reporting is incomplete. We examined the frequency of missing data in the OPTN/UNOS donor follow-up registry and found that reporting rates were low, particularly for donors who may have limited access to health care. We argue that a national donor follow-up registry is essential to ensure transparency in ascertaining long-term health outcomes among all living donors and in providing assessments of quality assurance within transplant programs. We have suggested approaches to strengthen the donor follow-up registry system. These include setting clear and high standards for follow-up reporting, a system of incentives and penalties that would motivate transplant centers to comply with these standards and would encourage donors to follow-up and lifelong follow-up reporting by primary care providers. We argue that the US government must provide funding to support a donor follow-up registry that can allow for meaningful and valid conclusions, in recognition of donors' public service and to maintain trust in the system of living organ donation. PMID- 22054025 TI - Cross-reactions vs co-sensitization evaluated by in silico motifs and in vitro IgE microarray testing. AB - BACKGROUND AND OBJECTIVE: Using an in silico allergen clustering method, we have recently shown that allergen extracts are highly cross-reactive. Here we used serological data from a multi-array IgE test based on recombinant or highly purified natural allergens to evaluate whether co-reactions are true cross reactions or co-sensitizations by allergens with the same motifs. METHODS: The serum database consisted of 3142 samples, each tested against 103 highly purified natural or recombinant allergens. Cross-reactivity was predicted by an iterative motif-finding algorithm through sequence motifs identified in 2708 known allergens. RESULTS: Allergen proteins containing the same motifs cross-reacted as predicted. However, proteins with identical motifs revealed a hierarchy in the degree of cross-reaction: The more frequent an allergen was positive in the allergic population, the less frequently it was cross-reacting and vice versa. Co sensitization was analyzed by splitting the dataset into patient groups that were most likely sensitized through geographical occurrence of allergens. Interestingly, most co-reactions are cross-reactions but not co-sensitizations. CONCLUSIONS: The observed hierarchy of cross-reactivity may play an important role for the future management of allergic diseases. PMID- 22054026 TI - Segmenting and targeting American university students to promote responsible alcohol use: a case for applying social marketing principles. AB - The current study contributes to the social marketing literature in the American university binge-drinking context in three innovative ways. First, it profiles drinking segments by "values" and "expectancies" sought from behaviors. Second, the study compares segment values and expectancies of two competing behaviors, that is, binge drinking and participation in alternative activities. Third, the study compares the influence of a variety of factors on both behaviors in each segment. Finally, based on these findings and feedback from eight university alcohol prevention experts, appropriate strategies to promote responsible alcohol use for each segment are proposed. PMID- 22054027 TI - Physician switching after drug request refusal. AB - Physician switching is a barometer of the quality of the relationship between a patient and a physician. Understanding the factors associated with physician switching in the context of direct-to-consumer advertising (DTCA) of prescription drugs has been largely unexamined. A total of 818 of 2,988 participants in a national telephone survey (27.4%) who had received DTCA reported asking their physician for a prescription drug, and 196 (24.0%) reported that their physician refused to prescribe the drug. Of those whose physicians refused, 13.9% (n = 27 of 194 with data) switched doctors. We found that individuals with regular medical-seeking behavior, full prescription drug coverage, with certain chronic conditions, and of African American origin were significantly more likely to switch physicians in this context. PMID- 22054028 TI - Are pharmaceutical marketing decisions calibrated to communications effects? AB - Marketing managers continually struggle with how to maximize the effects of an integrated marketing communications strategy. The growing number of available communication outlets, as well as highly varying competitive landscapes, adds further complexity to this challenge. This empirical study examines the differential impact within a pharmaceutical market therapeutic category where both "push" and "pull" communication strategies operate on consumers and gatekeepers alike, in an atmosphere of unrelenting product innovation and broad competition. Furthermore, we explore how two contingency variables-(a) the competitive landscape, and (b) the product's length of time on the market interact with these communication efforts and affect brand and category sales. PMID- 22054029 TI - Consumers young and old: segmenting the target markets for direct-to-consumer prescription drug advertising. AB - Direct-to-consumer pharmaceutical advertising (DTCA) studies have typically focused on older adults or a general population of adults. However, college students are viable targets for DTCA and are receiving more research attention in this area. In this article, we compare college students with two adult age segments. Our findings indicate all age groups had relatively high awareness of DTCA and similar attitudes and behavioral responses to the ads. However, there were significant differences in media use and health characteristics as well as the factors predicting DTCA ad trust, attitudes, and behavioral intentions. Implications and future research suggestions are discussed. PMID- 22054030 TI - Impact of locus of control on health message effectiveness. AB - This article examined how individuals' locus of control might moderate the effect of health message frames. An experiment was conducted whereby participants read either individual- or social-responsibility message frames after their locus of control was primed. Results indicated that messages presented in individual responsibility frames were more persuasive when people were primed with internal locus of control, whereas social-responsibility framed appeals were more persuasive when people were primed with external locus of control. These results were found for individuals in both high and low cognitive load conditions. Theoretical and practical implications of the findings are discussed. PMID- 22054031 TI - An exploratory study of adolescent female reactions to direct-to-consumer advertising: the case of the Human Papillomavirus (HPV) Vaccine. AB - When the human papillomavirus (HPV) vaccine was approved in 2006, an extensive direct-to-consumer (DTC) advertising campaign raised awareness and promoted vaccination. This study explores adolescents' exposure to and understanding of the messages in these advertisements. Sixty-seven African American females participated in a focus group about DTC advertising for the HPV vaccine. Virtually all adolescents had seen an HPV vaccine DTC advertisement, but most did not understand the health information contained in it. If DTC advertising is to be an effective source of health information for adolescents in the future, it must take into account the unique features of an adolescent audience. PMID- 22054033 TI - A clinical study to evaluate denture adhesive use in well-fitting dentures. AB - PURPOSE: The objective of this study was the assessment of retention and stability and functional benefits of denture adhesive applied to well-fitting and well-made dentures. MATERIALS AND METHODS: This was a randomized, crossover study to compare two marketed denture adhesives (test cream, Super Poligrip(r) Free, and test strip, Super Poligrip(r) Comfort Seal Strips) and an unmarketed cream adhesive (GlaxoSmith Kline Consumer Healthcare) with no adhesive as the negative control. Thirty-six subjects completed the study. One hour after the application of denture adhesive, retention and stability were measured using the Kapur Index and maxillary incisal bite force. Two hours after application, functional tests were used to assess denture movement and peanut particle migration under the denture. Subjects also rated confidence, comfort, satisfaction with dentures, and denture wobble in conjunction with the functional tests. RESULTS: Denture adhesives significantly (p < 0.05) improved retention and stability of well fitting dentures. Subjects experienced significantly (p < 0.05) fewer dislodgements while eating an apple after adhesive was applied to dentures. Significant (p < 0.05) increases in subjective ratings of confidence and comfort as well as decreases in denture wobble were associated with the use of adhesive. There was significant (p < 0.05) improvement in satisfaction ratings for cream adhesives. A single application of each denture adhesive was well tolerated. CONCLUSION: The results of this study provide evidence that use of Super Poligrip(r) denture adhesives can enhance aspects of performance of complete well fitting dentures as well as provide increased comfort, confidence, and satisfaction with dentures. PMID- 22054034 TI - Dynamic monitoring of metal oxide nanoparticle toxicity by label free impedance sensing. AB - The increased use of nanoparticles in industrial and medical products is driving the need for accurate, high throughput in vitro testing procedures to screen new particles for potential toxicity. While approaches using standard viability assays have been widely used, there have been increased reports of the interactions of nanoparticles with their soluble labels or optical readouts which raise concerns over the potential generation of false positive results. Here, we describe the use of an impedance spectroscopy approach to provide real-time reagent free detection of toxicity for a panel of metal oxide nanoparticles (ZnO, CuO, and TiO(2)). Using this approach, we show how impedance measurements can be used to track nanoparticle toxicity over time with comparable IC(50) values to those of standard assays (ZnO-55 MUg/mL, CuO-28 MUg/mL) as well as being used to identify a critical 6 h period following exposure during which the nanoparticles trigger rapid cellular responses. Through targeted analysis during this response period and the use of a novel image analysis approach, we show how the ZnO and CuO nanoparticles trigger the active export of intracellular glutathione via an increase in the activity of the ATP dependent MRP/1 efflux pumps. The loss of glutathione leads to increased production of reactive oxygen species which after 2.5 h triggers the cells to enter apoptosis resulting in a dose dependent cytotoxic response. This targeted testing strategy provides comprehensive information beyond that achieved with standard toxicity assays and indicates the potential for cell-nanoparticle interactions that could occur following in vivo exposure. PMID- 22054036 TI - DNA aneuploidy as a topographic malignant transformation pattern in a pleomorphic adenoma of long-term evolution: a case report. AB - INTRODUCTION: We present a case of long-term evolution of a submandibular pleomorphic adenoma. There is little information about topographic malignant transformation patterns of pleomorphic adenomas. CASE PRESENTATION: We extensively analyze a giant submandibular mixed tumor of 25-year evolution in a 57-year-old Caucasian woman. Deoxyribonucleic acid ploidy was evaluated in different superficial and deep areas using flow cytometry analysis and correlated with pathological and immunohistochemical characteristics. Superficial areas exhibited a typical histological pleomorphic adenoma pattern and were deoxyribonucleic acid diploid. Deep samples showed deoxyribonucleic acid aneuploidy, atypical histological benign features and expression of markers involved at an early-stage of malignant transformation, such as tumor protein 53 and antigen Ki67. CONCLUSION: These findings revealed that deep tumor compartments may be involved in the initial stages of malignant transformation. Deoxyribonucleic acid ploidy analysis may provide an additional diagnosis tool and indicate 'uncertain' areas that require careful study to avoid diagnostic errors. Larger studies are needed to confirm our results and to evaluate the usefulness of the technique. PMID- 22054035 TI - COPD association and repeatability of blood biomarkers in the ECLIPSE cohort. AB - BACKGROUND: There is a need for biomarkers to better characterise individuals with COPD and to aid with the development of therapeutic interventions. A panel of putative blood biomarkers was assessed in a subgroup of the Evaluation of COPD Longitudinally to Identify Surrogate Endpoints (ECLIPSE) cohort. METHODS: Thirty four blood biomarkers were assessed in 201 subjects with COPD, 37 ex-smoker controls with normal lung function and 37 healthy non-smokers selected from the ECLIPSE cohort. Biomarker repeatability was assessed using baseline and 3-month samples. Intergroup comparisons were made using analysis of variance, repeatability was assessed through Bland-Altman plots, and correlations between biomarkers and clinical characteristics were assessed using Spearman correlation coefficients. RESULTS: Fifteen biomarkers were significantly different in individuals with COPD when compared to former or non-smoker controls. Some biomarkers, including tumor necrosis factor-alpha and interferon-gamma, were measurable in only a minority of subjects whilst others such as C-reactive protein showed wide variability over the 3-month replication period. Fibrinogen was the most repeatable biomarker and exhibited a weak correlation with 6-minute walk distance, exacerbation rate, BODE index and MRC dyspnoea score in COPD subjects. 33% (66/201) of the COPD subjects reported at least 1 exacerbation over the 3 month study with 18% (36/201) reporting the exacerbation within 30 days of the 3-month visit. CRP, fibrinogen interleukin-6 and surfactant protein-D were significantly elevated in those COPD subjects with exacerbations within 30 days of the 3-month visit compared with those individuals that did not exacerbate or whose exacerbations had resolved. CONCLUSIONS: Only a few of the biomarkers assessed may be useful in diagnosis or management of COPD where the diagnosis is based on airflow obstruction (GOLD). Further analysis of more promising biomarkers may reveal utility in subsets of patients. Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation. TRIAL REGISTRATION: SCO104960, clinicaltrials.gov identifier NCT00292552. PMID- 22054037 TI - Thermal decomposition of pentacene oxyradicals. AB - The energetics and kinetics of the thermal decomposition of pentacene oxyradicals were studied using a combination of ab initio electronic structure theory and energy-transfer master equation modeling. The rate coefficients of pentacene oxyradical decomposition were computed for the range of 1500-2500 K and 0.01-10 atm and found to be both temperature and pressure dependent. The computational results reveal that oxyradicals with oxygen attached to the inner rings are kinetically more stable than those with oxygen attached to the outer rings. The latter decompose to produce CO at rates comparable to those of phenoxy radical, while CO is unlikely to be produced from oxyradicals with oxygen bonded to the inner rings. PMID- 22054038 TI - A new class of antimalarial dioxanes obtained through a simple two-step synthetic approach: rational design and structure-activity relationship studies. AB - A new series of simple endoperoxides, characterized by a 3-methoxy-1,2-dioxane scaffold, was designed on the basis of a previously developed pharmacophore. Through a simplified and versatile scheme of synthesis, which utilizes cheap and commercially available starting materials, it was possible to obtain several structurally and stereochemically different compounds that were tested against P. falciparum. Most of compounds showed antimalarial activity in the low micromolar range and no cellular toxicity, all being significantly more active on chloroquine resistant (CQ-R) than on chloroquine sensitive (CQ-S) strains. Resulting structure-activity relationships were analyzed by means of experimental and computational techniques, validating our design rationale and tailoring it for the new scaffold. Our study demonstrated that according to the hypothesized mechanism of action, the antimalarial activity can be improved through rational structural modifications, paving the way for the development of new simplified antimalarial endoperoxides. PMID- 22054040 TI - Erratum. PMID- 22054039 TI - Living kidney donor follow-up: state-of-the-art and future directions, conference summary and recommendations. AB - In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented. PMID- 22054042 TI - Patient-controlled intrathecal analgesia for the management of breakthrough cancer pain: a retrospective review and commentary. AB - OBJECTIVE: Intrathecal therapy (ITT) via an implanted pump has become an accepted practice for the treatment of refractory cancer pain by infusing opioids and adjuncts directly to the neuraxis. Until recently, only a programmed basal rate of infusion could be delivered, and therefore, breakthrough pain required ongoing use of oral or transmucosal opioids. Recently, an implanted pump manufacturer has introduced a handheld device to bolus additional medication for breakthrough pain. We hypothesize that patient-controlled intrathecal analgesia (PCIA) for the treatment of breakthrough cancer pain reduces the need for breakthrough opioids and improves the patient perception of pain. METHODS: A retrospective chart review was done on all patients who underwent ITT for cancer pain between January 2009 and February 2011. Clinical outcomes of interest were reduction in nonintrathecal opioid use and reduction in numerical rating score (NRS) for pain. The data was collected prior to ITT and at a 4-6 week postimplant visit. RESULTS: After initiation of ITT with PCIA, 50% of patients had discontinued all nonintrathecal opioids at follow-up, and 46% of the patients on breakthrough medications no longer required their use. At follow-up, there was a significant reduction in total nonintrathecal opioid use, with an average of 796 mg pre-ITT vs 64 mg post-ITT of daily oral morphine equivalent dosing (P = <0.001). There was a significant difference between mean NRS pain score at follow up-6.5 vs 3.1 pre-ITT (P<0.001). 65% of patients reported their pain as severe (NRS of 7 or greater) prior to ITT; this decreased to 3% at follow-up. CONCLUSIONS: In patients with refractory cancer pain, intrathecal drug therapy with PCIA is associated with improved pain reporting, reduced nonintrathecal around-the-clock, and breakthrough opioid requirements. PMID- 22054045 TI - Epidemiology of invasive Candida infection in a neonatal intensive care unit in France. PMID- 22054046 TI - Effects of whole-body vibration on postural control in elderly: a systematic review and meta-analysis. AB - BACKGROUND: This systematic review was performed to summarize the current evidence for whole body vibration (WBV) interventions on postural control in elderly. METHODS: English and German language papers in Medline, PEDro, Cinahl and the Cochrane databases were searched. Two reviewers extracted data on patients' characteristics, type of WBV intervention and outcomes. Two independent reviewers rated the methodological quality of these studies. Data were pooled using random-effects meta-analysis. RESULTS: Fifteen papers reporting quantitative data were included. Results from 15 papers could be pooled for a meta-analysis. The studies involved 933 participants. In 7 studies the authors investigated the effects of vibration plates generating vertical sinusoidal vibrations (VS-WBV) and 7 papers described the use of side-alternating sinusoidal vibrations (SS-WBV). One study investigated both VS-WBV and SS-WBV.Weak to moderate evidence of an overall effect as a result of VS-WBV and SS-WBV was observed for (a) static balance for post-intervention values with a standardized mean difference (SMD) -0.06, 95% CI -0.31 to 0.18 and for change values SMD 0.26, 95% CI -1.09 to 0.57, and (b) dynamic balance for post-intervention-values SMD -0.34, 95% CI -0.60 to -0.08. For functional balance (c) an overall outcome for post-intervention values with SMD of 0.34, 95% CI -0.19 to 0.87 was found. CONCLUSIONS: The 15 studies reviewed were of moderate methodological quality. In summary, SS-WBV seems to have a beneficial effect on dynamic balance in elderly individuals. However, the current results should be interpreted with caution because of the observed heterogeneity of training parameters and statistical methods. Future studies are warranted to evaluate the effects of WBV on postural control in an elderly population. PMID- 22054048 TI - Polarized naphthalimide CH donors enhance Cl- binding within an aryl-triazole receptor. AB - The dipolar character of 1,8-naphthalimide together with polarization of the C(4) H and C(5)-H donors has been utilized in receptor 1 to effectively bind chloride alongside triazole and phenylene units. The Cl(-) binding strength of 1 shows that the naphthalimide provides greater anion stabilization than an unactivated phenylene, and DFT calculations show that its collinear donor array can be a "urea-like" analog for CH...anion interactions. PMID- 22054047 TI - Improving collision induced dissociation (CID), high energy collision dissociation (HCD), and electron transfer dissociation (ETD) fourier transform MS/MS degradome-peptidome identifications using high accuracy mass information. AB - MS dissociation methods, including collision induced dissociation (CID), high energy collision dissociation (HCD), and electron transfer dissociation (ETD), can each contribute distinct peptidome identifications using conventional peptide identification methods (Shen et al. J. Proteome Res. 2011), but such samples still pose significant informatics challenges. In this work, we explored utilization of high accuracy fragment ion mass measurements, in this case provided by Fourier transform MS/MS, to improve peptidome peptide data set size and consistency relative to conventional descriptive and probabilistic scoring methods. For example, we identified 20-40% more peptides than SEQUEST, Mascot, and MS_GF scoring methods using high accuracy fragment ion information and the same false discovery rate (FDR) from CID, HCD, and ETD spectra. Identified species covered >90% of the collective identifications obtained using various conventional peptide identification methods, which significantly addresses the common issue of different data analysis methods generating different peptide data sets. Choice of peptide dissociation and high-precision measurement-based identification methods presently available for degradomic-peptidomic analyses needs to be based on the coverage and confidence (or specificity) afforded by the method, as well as practical issues (e.g., throughput). By using accurate fragment information, >1000 peptidome components can be identified from a single human blood plasma analysis with low peptide-level FDRs (e.g., 0.6%), providing an improved basis for investigating potential disease-related peptidome components. PMID- 22054044 TI - European adolescents' level of perceived stress is inversely related to their diet quality: the Healthy Lifestyle in Europe by Nutrition in Adolescence study. AB - As stress is hypothesised to influence dietary behaviour, the relationship between perceived stress and diet quality in European adolescents was investigated. Within the Healthy Lifestyle in Europe by Nutrition in Adolescence study, adolescents (n 704, aged 12-17 years) from schools in five European cities (Ghent, Stockholm, Zaragoza, Athens and Vienna) completed a 2 d 24 h dietary recall assessment and an Adolescent Stress Questionnaire. Measurements and information were taken on height, weight, pubertal stage, parental education level, the level of moderate-to-vigorous physical activity (MVPA) and sleep duration. The Diet Quality Index for Adolescents (DQI-A) was calculated from the dietary data, which comprised three components reflecting dietary diversity, quality and equilibrium. Hierarchical linear models were performed to investigate the relationship between the adolescents' level of perceived stress and the DQI-A and its components, adjusting for relevant covariates (age, BMI z-score, pubertal stage and parental education). These models were additionally adjusted for MVPA or sleep duration. In both boys and girls, perceived stress was a significant independent negative predictor for their overall DQI-A. This inverse relationship was observed for all dietary components, except for dietary diversity in boys, and it was unaltered when additionally adjusted for MVPA or sleep duration. The observed inverse relationship between stress and diet quality within these European adolescents supports the hypothesis that stress influences dietary behaviour, thus emphasising the need for preventive stress-coping strategies for adolescents. PMID- 22054051 TI - Longitudinal study of 29 patients with Meniere's disease with follow-up of 10 years or more (In commemoration of Professor Emeritus Isamu Watanabe). AB - CONCLUSIONS: A final incidence of bilateral involvement was 20.7%. Episodic spells of vertigo were completely controlled in 23 of 29 patients, while 11 of 29 patients demonstrated over 70 dB hearing loss. OBJECTIVE: To analyze the clinical course of 29 patients with Meniere's disease during follow-up of 10 years or more. METHODS: The subjects were 29 patients with a mean follow-up of 18.3 years. The hearing level was measured by the pure tone average (PTA) of four frequencies at the initial and the final examination, and it was classified into four categories according to the American Academy of Otolaryngology-Head and Neck Society (AAO-HNS) criteria. The control of vertigo was evaluated by the modified AAO-HNS criteria. RESULTS: At enrolment two patients had bilateral involvement. In the period of follow-up, bilateral involvement emerged in four more patients. The hearing levels at the final examinations were as follows: 3 patients, <25 dB; 6 patients, 26-40 dB; 9 patients, 41-70 dB; and 11 patients, >70 dB. The control of vertigo according to the modified AAO-HNS guideline was class A in 23 patients, class B in 2 patients, and class C in 1 patient; the remaining 3 patients could not be evaluated. PMID- 22054049 TI - Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors. AB - BACKGROUND: Mesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic efficacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells. METHODS: We assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID(50) assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofluorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods. RESULTS: Adv-Stat3(-) amplified in MSCs and were released 4 days after infection. MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confirmed the preferential localization of MSCs in the tumor periphery 24 hours after tail vein injection, and this localization was mainly detected in the tumor parenchyma after 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice. CONCLUSIONS: These results indicate that MSCs migrate to the tumor site in a time dependent manner and could be an effective platform for the targeted delivery of CRAd and the amplification of tumor killing effects. PMID- 22054050 TI - Continuation of quetiapine versus switching to placebo or lithium for maintenance treatment of bipolar I disorder (Trial 144: a randomized controlled study). AB - OBJECTIVE: Quetiapine, combined with lithium or divalproex, demonstrates efficacy in the maintenance treatment of bipolar I disorder. This study investigated the efficacy and safety of quetiapine monotherapy as maintenance treatment in bipolar I disorder compared with switching to placebo or lithium. METHOD: Patients aged >= 18 years with DSM-IV-diagnosed bipolar I disorder and a current or recent manic, depressive, or mixed episode received open-label quetiapine (300-800 mg/d) for 4-24 weeks. Patients achieving stabilization were randomized to continue quetiapine or to switch to placebo or lithium (0.6-1.2 mEq/L) for up to 104 weeks in a double-blind trial. Outcome measures included times to recurrence of any mood event (primary outcome measure), manic event, or depressive event. Safety assessments included adverse events and laboratory values. The study was terminated early after planned interim analysis provided positive results. The study was conducted between March 2005 and July 2007. RESULTS: Of 2,438 patients starting open-label quetiapine, 1,226 (50.3%) were randomized to double-blind treatment, including 1,172 (95.6%) in the intent-to-treat population. Time to recurrence of any mood event was significantly longer for quetiapine versus placebo (hazard ratio [HR] = 0.29; 95% CI, 0.23-0.38; P < .0001) and for lithium versus placebo (HR = 0.46; 95% CI, 0.36-0.59; P < .0001). Quetiapine and lithium significantly increased time to recurrence of both manic events (quetiapine: HR = 0.29; 95% CI, 0.21-0.40; P < .0001; lithium: HR = 0.37; 95% CI, 0.27-0.53; P < .0001) and depressive events (quetiapine: HR = 0.30; 95% CI, 0.20-0.44; P < .0001; lithium: HR = 0.59; 95% CI, 0.42-0.84; P < .004) compared with placebo. Overall rates of adverse events were generally similar between treatment groups, and safety findings for quetiapine were consistent with its known profile. CONCLUSIONS: In patients stabilized during acute quetiapine treatment, continuation of quetiapine significantly increased time to recurrence of any mood, manic, or depressive event compared with switching to placebo. Switching to lithium was also more effective than placebo for the prevention of manic and depressive events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00314184. PMID- 22054052 TI - Retraction: The cellular source for APOBEC3G's incorporation into HIV-1. PMID- 22054053 TI - Re: Relationship between ventricular dyssynchrony and T-wave alternans in patients with coronary artery disease. PMID- 22054054 TI - On the crucial importance of the pH for the formation and self-stabilization of protein microgels and strands. AB - Stable suspensions of protein microgels are formed by heating salt-free beta lactoglobulin solutions at concentrations up to about C = 50 g.L(-1) if the pH is set within a narrow range between 5.75 and 6.1. The internal protein concentration of these spherical particles is about 150 g.L(-1) and the average hydrodynamic radius decreases with increasing pH from 200 to 75 nm. The formation of the microgels leads to an increase of the pH, which is a necessary condition to obtain stable suspensions. The spontaneous increase of the pH during microgel formation leads to an increase of their surface charge density and inhibits secondary aggregation. This self-stabilization mechanism is not sufficient if the initial pH is below 5.75 in which case secondary aggregation leads to precipitation. Microgels are no longer formed above a critical initial pH, but instead short, curved protein strands are obtained with a hydrodynamic radius of about 15-20 nm. PMID- 22054055 TI - Pharmacokinetics, metabolism and excretion of 14C-monoethyl phthalate (MEP) and 14C-diethyl phthalate (DEP) after single oral and IV administration in the juvenile dog. AB - The pharmacokinetics, metabolism and excretion of monoethyl phthalate (MEP) and diethyl phthalate (DEP) were compared after intravenous or oral administration of [(14)C]MEP or [(14)C]DEP in juvenile beagle dogs. Four male juvenile beagle dogs were treated with a single oral or bolus intravenous dose of either [(14)C]MEP or [(14)C]DEP (164 MUg/kg). The absorption, metabolism, excretion and pharmacokinetics of [(14)C]MEP and [(14)C]DEP were nearly identical. [(14)C]DEP was rapidly and nearly completely metabolized to [(14)C]MEP following either intravenous or oral administration. [(14)C]MEP and[(14)C]DEP were rapidly absorbed, the elimination half-life was estimated to be 1 hour. Approximately 90% 96% of the dose was excreted in urine with 2%-3% of the dose in faeces. MEP accounted for the majority of the dose in plasma and urine; in addition, three minor metabolites (M1, M2 and M3) were detected. The minor metabolites were neither phthalic acid nor glucuronide/sulfate conjugates. The nearly identical metabolism and pharmacokinetics of MEP and DEP in juvenile dogs justifies the use of DEP toxicity data in the risk assessment of MEP exposure. PMID- 22054056 TI - Addressing patients' information needs: a first evaluation of a question prompt sheet in the pretreatment consultation for patients with esophageal cancer. AB - This study aims to develop and pilot a question prompt sheet to assist esophageal cancer patients to obtain desired information in the consultation in which potentially curative esophagectomy is discussed. Whether a prompt sheet affected patients' question asking, the number and scope of topics discussed, the length of the consultation, and patients' satisfaction is investigated. Patients (n= 30) were randomized either to receive care as usual (control group) or to receive a prompt sheet (intervention group). All patients completed a baseline questionnaire, their consultations were audio-recorded and content-coded, and they received a structured telephone interview 2 days after the consultation to assess satisfaction. Patients provided with the prompt sheet marked a median of 19 questions. They asked significantly more questions as compared with patients in the control group (median of 12 vs. 8 questions). Questions mainly addressed treatment options and procedures. No differences were found with regard to consultation length and patient satisfaction. Our results suggest that providing patients with a simple, easy-to-implement tool such as a question prompt is appreciated and helps patients to ask more questions during the consultation without increasing the length of the consultation. PMID- 22054057 TI - A mechanistic study of the 2-thienylmethyl + HO2 radical recombination reaction. AB - Radical recombination reactions are important in the combustion of fuel oils. Shale oil contains alkylated heteroaromatic species, the simplest example of which is the 2-thienylmethyl radical. The ab initio potential energy surface for the reaction of the 2-thienylmethyl radical with the HO(2) radical has been examined. Seventeen product channels corresponding to either addition/elimination or direct hydrogen abstraction have been characterized for the first time. Direct hydrogen abstract from HO(2) proceeds via a weakly bound van der Waals complex, which leads to 2-methylthiophene, 2-methylene-2,3-dihydrothiophene, or 2 methylene-2,5-dihydrothiophene depending upon the 2-thienylmethyl radical reaction site. The addition pathway for the two radical reactants is barrierless with the formation of three adducts, as distinguished by HO(2) reaction at three different sites on the 2-thienylmethyl radical. The addition is exothermic by 37 55 kcal mol(-1) relative to the entrance channel, and these excess energies are available to promote further decomposition or rearrangement of the adducts, leading to nascent products such as H, OH, H(2)O, and CH(2)O. The reaction surfaces are characterized by relatively low barriers (most lower than 10 kcal mol(-1)). Upon the basis of a careful analysis of the overall barrier heights and reaction exothermicities, the formations of O(2), OH, and H(2)O are likely to be important pathways in the radical recombination reactions of 2-thienylmethyl + HO(2). PMID- 22054058 TI - Synthesis of monomeric derivatives to probe memoquin's bivalent interactions. AB - Eight monomeric congeners, related to the multitarget lead candidate memoquin, were prepared and evaluated at multiple targets to determine their profile against Alzheimer's disease. 2-4 bind to AChE with similar low nanomolar affinities and function as effective inhibitors of amyloid aggregation. The most potent monovalent ligand 2 also inhibits BACE-1 in vitro and APP metabolism in primary chicken telencephalic neurons. PMID- 22054059 TI - Gilles de la Tourette's syndrome in a patient with 47(XXX) syndrome: a case report. AB - INTRODUCTION: To the best of our knowledge, this is the first report of a comorbidity between Gilles de la Tourette's syndrome and 47 (XXX) syndrome. The clinical picture of Gilles de la Tourette's Syndrome is well described, while 47 (XXX) syndrome is much more rare and has a broader spectrum of possible phenotypic presentations. CASE PRESENTATION: An Italian Caucasian girl was referred at the age of 11 to our Rehabilitation Center for anxiety and learning difficulties. The girl had already been diagnosed as having 47(XXX) syndrome; she had some rather typical features of the chromosomal abnormality, but she also showed a high level of anxiety and the presence of motor and vocal tics. When an accurate history was taken, a diagnosis of Gilles de la Tourette's Syndrome emerged. CONCLUSIONS: The possible interaction between peculiar features of these two syndromes in terms of neuropsychological and affective functioning is both interesting for the specific case and to hypothesize models of rehabilitation for patients with one or both syndromes. Executive functions are specifically reduced in both syndromes, therefore it might be hard to discriminate the contribution of each one to the general impairment; the same applies to anxiety. Moreover, mental retardation (with a significantly lower verbal cognitive functioning) poses relevant problems when suggesting cognitive behavioral or psychoeducational rehabilitative approaches. PMID- 22054061 TI - Current status of organ transplantation in Japan. AB - To overcome severe donor shortage, Japanese doctors over the years have developed innovative strategies to maximize organs transplanted per brain death donor and expanded the donor pool using living donors. They also used living and marginal organs and drastically improved living donor lung, liver, pancreas and kidney transplantations. Moreover, they initiated ABO blood type incompatible liver transplantation advancements and succeeded in overcoming the blood type barrier in kidney and liver transplantations. Similar efforts are underway for pancreas transplantation. Furthermore, Japanese doctors have developed a nonaggressive step to achieve immunosuppression following organ transplantation by carefully monitoring donor-specific hyporesponsiveness and infectious immunostatus. However, the institution of amendments to allocation systems and the intensification of efforts to decrease living donor morbidity and to increase the number of brain death donors have remained important issues needing attention. Overall, the strategies Japan has adopted to overcome donor shortage can provide useful insights on how to increase organ transplantations. PMID- 22054060 TI - Exogenous interleukin-6, interleukin-13, and interferon-gamma provoke pulmonary abnormality with mild edema in enterovirus 71-infected mice. AB - BACKGROUND: Neonatal mice developed neurological disease and pulmonary dysfunction after an infection with a mouse-adapted human Enterovirus 71 (EV71) strain MP4. However, the hallmark of severe human EV71 infection, pulmonary edema (PE), was not evident. METHODS: To test whether EV71-induced PE required a proinflammatory cytokine response, exogenous pro-inflammatory cytokines were administered to EV71-infected mice during the late stage of infection. RESULTS: After intracranial infection of EV71/MP4, 7-day-old mice developed hind-limb paralysis, pulmonary dysfunction, and emphysema. A transient increase was observed in serum IL-6, IL-10, IL-13, and IFN-gamma, but not noradrenaline. At day 3 post infection, treatment with IL-6, IL-13, and IFN-gamma provoked mild PE and severe emphysema that were accompanied by pulmonary dysfunction in EV71 infected, but not herpes simplex virus-1 (HSV-1)-infected control mice. Adult mice did not develop PE after an intracerebral microinjection of EV71 into the nucleus tractus solitarii (NTS). While viral antigen accumulated in the ventral medulla and the NTS of intracerebrally injected mice, neuronal loss was observed in the ventral medulla only. CONCLUSIONS: Exogenous IL-6, IL-13, and IFN-gamma treatment could induce mild PE and exacerbate pulmonary abnormality of EV71 infected mice. However, other factors such as over-activation of the sympathetic nervous system may also be required for the development of classic PE symptoms. PMID- 22054062 TI - Stigmatization of patients with chronic pain: the extinction of empathy. AB - OBJECTIVE: To address how health professionals may inadvertently contribute to the stigmatization of patients with chronic pain. SETTING: Formulation and implementation of the Australian National Pain Strategy. DESIGN: Review of current concepts of stereotyping and stigma, consideration of their relationship to empathy, and how they might impinge upon the clinical encounter. FINDINGS: The extinction of empathy, which we refer to as "negative empathy," can overwhelm health professionals, allowing the entry of negative community stereotypes of chronic pain sufferers and add to their stigmatization. Prevailing dualistic frames of reference encourage this process. CONCLUSION: Greater awareness by health professionals of their own potential, often inadvertent, contribution to the stigmatization of their patients with chronic pain may serve as a basis for an expanded model of clinical engagement. PMID- 22054064 TI - Comparative effects of six probiotic strains on immune function in vitro. AB - There is considerable interest in the strain specificity of immune modulation by probiotics. The present study compared the immunomodulatory properties of six probiotic strains of different species and two genera in a human peripheral blood mononuclear cell (PBMC) model in vitro. Live cells of lactobacilli (Lactobacillus casei Shirota, L. rhamnosus GG, L. plantarum NCIMB 8826 and L. reuteri NCIMB 11951) and bifidobacteria (Bifidobacterium longum SP 07/3 and B. bifidum MF 20/5) were individually incubated with PBMC from seven healthy subjects for 24 h. Probiotic strains increased the proportion of CD69+ on lymphocytes, T cells, T cell subsets and natural killer (NK) cells, and increased the proportion of CD25+, mainly on lymphocytes and NK cells. The effects on activation marker expression did not appear to be strain specific. NK cell activity was significantly increased by all six strains, without any significant difference between strains. Probiotic strains increased production of IL-1beta, IL-6, IL-10, TNF-alpha, granulocyte-macrophage colony-stimulating factor and macrophage inflammatory protein 1alpha to different extents, but had no effect on the production of IL-2, IL-4, IL-5 or TNF-beta. The cytokines that showed strain specific modulation included IL-10, interferon-gamma, TNF-alpha, IL-12p70, IL-6 and monocyte chemotactic protein-1. The Lactobacillus strains tended to promote T helper 1 cytokines, whereas bifidobacterial strains tended to produce a more anti inflammatory profile. The results suggest that there was limited evidence of strain-specific effects of probiotics with respect to T cell and NK cell activation or NK cell activity, whereas production of some cytokines was differentially influenced by probiotic strains. PMID- 22054065 TI - Histone deacetylase inhibition by sodium valproate regulates polarization of macrophage subsets. AB - Recent studies suggest that change of macrophage phenotype (M1/M2) is associated with autoimmune diseases. Sodium valproate (VPA) is a class I histone deacetylase (HDAC) inhibitor, which has immunomodulatory function in graft-versus-host disease. However, its impact on macrophage polarization has not been defined. We evaluated the effects of VPA on both mouse macrophage cell line RAW264.7 and primary mouse bone marrow macrophages (BMMs). Exposure to VPA significantly repressed the production of interleukin 12 (IL-12), and tumor necrosis factor alpha by lipopolysaccharide (LPS)-induced macrophage activation, in contrast, promoted IL-10 expression. VPA also affected the costimulatory molecule expression on LPS-stimulated RAW264.7 and BMMs (downregulation of CD40 and CD80, and upregulation of CD86). Specifically, VPA inhibited macrophage-mediated T helper 1 (Th1) effector but enhanced Th2 effector cell activation. Together, our preclinical study demonstrates that VPA significantly affects the phenotype and function of macrophage, indicating an important role of HDAC activity in immune regulation and inflammation. It also provides a rationale to evaluate VPA activity for the treatment of macrophage dysfunction-associated diseases. PMID- 22054066 TI - Characterization of the human ornithine transcarbamylase 3' untranslated regulatory region. AB - Mutations in the untranslated regulatory regions of genes may result in abnormal gene expression or transcriptional regulation. In this study, we characterize the ornithine transcarbamylase (OTC) mRNA isoforms of the X-linked OTC gene involved in the urea formation in the liver. Our data revealed that two major transcripts (OTC-t1 and OTC-t2) are more highly expressed than any of the other isoforms in all the tissues analyzed, though a longer transcript (OTC-t3) was also isolated and characterized from the brain sample. The OTC-t2 sequence fully matches the OTC mRNA reference sequence (NM_000531.5). All three isoforms use a canonical AAUAAA hexamer that is predicted to fold into a hairpin secondary structure which might be exposed to the cleavage and polyadenylation specificity factor. In addition, we observed that the OTC-t1 and OTC-t2 transcripts display heterogeneity at the cleavage sites in a tissue-dependent manner. Taken together, our data demonstrate that several mRNA isoforms are transcribed from the OTC gene, thereby indicating a wide degree of variability in post-transcriptional regulation. PMID- 22054067 TI - Impact of glutathione transferase M1, T1, and P1 gene polymorphisms in the genetic susceptibility of North Indian population to renal cell carcinoma. AB - In this study, we investigated the association of GSTP1, GSTM1, and GSTP1 genetic variants with renal cell carcinoma (RCC) among North Indian patients. The difference in frequency of the GSTT1 null genotype between cases and control subjects was statistically significant (active ver. null, odds ratio [OR]=0.368; confidence intervals [CI] 95%=0.243-0.557, p=0.001). The differences in the frequency of GSTP1 genotypes were statistically significant (AA ver. AG/GG, OR=1.879; CI 95%=0.355-0.797, p=0.002). Higher allelic frequency of the GSTP1 G allele was associated with RCC cases (G ver. A allele, OR=1.534; 95% CI=1.159 2.030, p=0.003). The gene-gene interaction in terms of three-way combination of GSTM1 null, GSTT1 null, and GSTP1 (AG/GG) resulted in 4.5-fold increase in RCC risk (OR=4.452; 95% CI=2.220-9.294). Similarly, our study revealed that GST polymorphism might be a vital determinant of advancement to higher pathological stages and histological grades of RCC. Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to RCC and its progression. PMID- 22054068 TI - Endothelial nitric oxide synthase gene polymorphisms (G894T, 4b/a and T-786C) and preeclampsia: meta-analysis of 18 case-control studies. AB - Studies investigating the association between endothelial nitric oxide synthase (eNOS) gene polymorphisms and preeclampsia reported contradictory or nonconclusive results. We performed a meta-analysis of 18 genetic association studies that examined the relationship between preeclampsia and the G894T, 4a/b and T-786C polymorphisms of the eNOS gene. Subgroup analysis by ethnicity and potential sources of heterogeneity and bias were explored. The MEDLINE, EMBASE, and Google Scholar databases were searched to access the relevant genetic association studies up to June 2011. For the allelic analysis of the G894T variant, all studies showed no significant association. For the genotypic analysis, the combined studies of the G allele showed negative significance (odds ratio [OR]=0.56; 95% confidence interval [CI]: 0.33-0.97), all the studies showed positively significance when the T allele was combined (OR=1.17; 95% CI: 1.01 1.36), and results were also positively significant in non-Asian populations (OR=1.20; 95% CI: 1.02-1.43). For the allelic analysis of the 4b/a variant, all studies showed no significant association, but results were negatively significant in non-Asian populations (OR=0.67; 95% CI: 0.46-0.98). For the genotype analysis, combined studies of the b allele showed negative significance (OR=0.55; 95% CI: 0.36-0.84). Moreover, non-Asian studies showed negatively significant results (OR=0.45; 95% CI: 0.28-0.72). For the analysis of the T-786C variant, none of the studies showed significant results. The synthesis of available evidence supports the fact that intron 4a allele, homozygosity for the 894T and intron 4a of eNOS are positively associated with preeclampsia. Large, multiethnic confirmatory, and well-designed studies are needed to determine the relation between preeclampsia and polymorphisms of the eNOS gene. PMID- 22054069 TI - Reducing malaria misdiagnosis: the importance of correctly interpreting Paracheck Pf(r) "faint test bands" in a low transmission area of Tanzania. AB - BACKGROUND: Although malaria rapid diagnostic tests (RDTs) have been extensively evaluated since their introduction in the early 1990's, sensitivity and specificity vary widely limiting successful integration into clinical practice. This paper reviews specific issues surrounding RDT use in field settings and presents results of research investigating how to interpret "faint test bands" on ParaCheck Pf(r) in areas of low transmission in order to reduce malaria misdiagnosis. METHODS: A multi-phase cross-sectional study was conducted at a remote hospital in the northern Tanzanian highlands. Capillary blood samples were taken from consenting participants (n = 319) for blood smear and ParaCheck Pf(r) testing. Primary outcome variables were sensitivity, specificity and proportion misdiagnosed by ParaCheck Pf(r) and local microscopy. ParaCheck Pf(r) "faint bands" were classified as both true positives or true negatives during evaluation to determine appropriate clinical interpretation. Multivariate logistic regression adjusted for age and gender was conducted to determine odds of misdiagnosis for local microscopy and ParaCheck Pf(r). RESULTS: Overall, 23.71% of all ParaCheck Pf(r) tests resulted in a "faint band" and 94.20% corresponded with true negatives. When ParaCheck Pf(r) "faint bands" were classified as positive, specificity was 75.5% (95% CI = 70.3%-80.6%) as compared to 98.9% (95% CI = 97.0%-99.8%) when classified as negative. The odds of misdiagnosis by local microscopy for those > 5 years as compared to those <= 5 years are 0.370 (95% CI = 0.1733-0.7915, p = 0.010). In contrast, even when ParaCheck Pf(r) faint bands are considered positive, the odds of misdiagnosis by ParaCheck Pf(r) for those > 5 years as compared to those <= 5 years are 0.837 (95% CI = 0.459-1.547, p = 0.5383). CONCLUSIONS: We provide compelling evidence that in areas of low transmission, "faint bands" should be considered a negative test when used to inform clinical decision-making. Correct interpretation of RDT test bands in a clinical setting plays a central role in successful malaria surveillance, appropriate patient management and most importantly reducing misdiagnosis. PMID- 22054070 TI - Sleep architecture in healthy 5-year-old preschool children: associations between sleep schedule and quality variables. AB - AIM: Although disturbed sleep quality such as night awakenings and difficulties in falling asleep are common symptoms during sleep in preschool children, relationships between sleep quality and sleep schedule are mostly unknown. This study aimed to evaluate the relationships between sleep schedule and quality variables in preschool children. METHODS: Sleep-wake patterns of 48 healthy 5 year-old children were assessed over 7 consecutive days using actigraphy. RESULTS: Children with longer sleep latency had a lower sleep quality, a later bedtime, a later sleep onset time, a shorter nocturnal sleep period and a longer daytime nap. Children with a longer nocturnal sleep period on weekends compared with weekdays had longer sleep latency and a later sleep onset time on weekdays, resulting in a lower sleep quality on weekends. An irregular bedtime on weekdays was associated with a later sleep onset time and a shorter sleep period on weekends. CONCLUSION: Sleep quality and schedule were linked with each other, which may explain why sleep problems tend to aggregate and form a wider syndrome of disturbed sleep even in young children. Strategies solely targeting the improvement of sleep quantity may not promote ideal sleep; simultaneous considerations for the sleep rhythm and quality may be required. PMID- 22054071 TI - Proteomics of Pseudomonas aeruginosa Australian epidemic strain 1 (AES-1) cultured under conditions mimicking the cystic fibrosis lung reveals increased iron acquisition via the siderophore pyochelin. AB - Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). While most CF patients are thought to acquire P. aeruginosa from the environment, person-to person transmissible strains have been identified in CF clinics worldwide, and the molecular basis for transmissibility remains poorly understood. We undertook a complementary proteomics approach to characterize protein profiles from a transmissible, acute isolate of the Australian epidemic strain 1 (AES-1R), the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1 when grown in an artificial medium that mimics the CF lung environment compared to growth in standard laboratory medium. Proteins elevated in abundance in AES-1R included those involved in methionine and S adenosylmethionine biosynthesis and in the synthesis of phenazines. Proteomic data were validated by measuring culture supernatant levels of the virulence factor pyocyanin, which is the final product of the phenazine pathway. AES-1R and PAO1 released higher extracellular levels of pyocyanin compared to PA14 when grown in conditions that mimic the CF lung. Proteins associated with biosynthesis of the iron-scavenging siderophore pyochelin (PchDEFGH and FptA) were also present at elevated abundance in AES-1R and at much higher levels than in PAO1, whereas they were reduced in PA14. These protein changes resulted phenotypically in increased extracellular iron acquisition potential and, specifically, elevated pyochelin levels in AES-1R culture supernatants as detected by chrome azurol-S assay and fluorometry, respectively. Transcript analysis of pyochelin genes (pchDFG and fptA) showed they were highly expressed during the early stage of growth in artificial sputum medium (18 h) but returned to basal levels following the establishment of microcolony growth (72 h) consistent with that observed in the CF lung. This provides further evidence that iron acquisition by pyochelin may play a role in the early stages of transmissible CF infection associated with AES-1R. PMID- 22054072 TI - Rates of upgrade of ICD recipients to CRT in clinical practice and the potential impact of the more liberal use of CRT at initial implant. AB - BACKGROUND: Many implantable cardioverter defibrillator (ICD) recipients may develop indications for cardiac resynchronization therapy (CRT) during follow-up. However, the actual upgrade rate during follow-up in clinical practice is not known. METHODS: We performed a single center retrospective observational study of all new ICD implants over 5 years (2003-2007). The rate of CRT upgrade of patients initially implanted with a single-/dual-chamber ICD during follow-up was assessed. The impact of using alternative criteria on the need for CRT in ICD recipients at initial implant was also evaluated. RESULTS: During the study period, there were 549 new ICD implants. The initial implant was a single/dual chamber ICD in 73% (n = 399) and a CRT-D in 27% (n = 150). During follow-up (48+/ 20 months) of the 399 ICD recipients, 70 (17.5%) died and 15 (3.8%) were upgraded to CRT, including eight cases where left ventricular lead implant had been initially unsuccessful. Upgrade rates at 1, 3, and 5 years were 0.03%, 2.4%, and 5.1%, respectively. Using alternative CRT criteria (left ventricular ejection fraction [LVEF]<=30%, QRS >=130 ms, New York Heart Association I-IV) 42.6% (n = 234) of ICD recipients met criteria for CRT at initial implant. CONCLUSION: In this retrospective single center study, rates of CRT upgrade in ICD recipients over the medium term were low, which may reflect underuse in otherwise appropriate candidates. The more liberal use of CRT at initial implant in patients with a reduced LVEF, a broad QRS, but only mild heart failure symptoms would require approximately 50% increase in CRT use in ICD recipients at initial implant, and may help address some of the suggested underutilization. PMID- 22054073 TI - Time trend analysis of mastoidectomy procedures performed in Ontario, 1987-2007. AB - CONCLUSIONS: There has been a reduction in the number of modified radical mastoidectomy and revision mastoidectomy surgeries per head of population in Ontario between 1987 and 2007, we believe that this represents a true reduction in prevalence of cholesteatoma. The increase of cases performed at the University Hospital Network, Toronto (UHN) may represent a shift to subspecialization in the treatment of chronic ear disease. OBJECTIVE: To analyze the trends in mastoid operations for chronic middle ear disease in the Canadian province of Ontario between 1987 and 2007 and to determine whether an increasing proportion of these procedures are being performed in tertiary referral centres. METHODS: The year on year population and number of mastoid procedures performed per year in Ontario and at the UHN between 1987 and 2007 were obtained from Statistics Canada and the Ministry of Health and Long-Term Care, Ontario, respectively. Population-adjusted rates of mastoid surgery for Ontario and the UHN. These data were collated and graphically represented for trend analysis. RESULTS: The population-adjusted number of mastoid procedures for Ontario declined from 7.1 cases per 100,000 in 1986 to 4.1 cases per 100,000 in 2006. During this time the number of both modified radical mastoidectomies and revision mastoid surgeries at UHN increased. PMID- 22054075 TI - HSQC-1,1-ADEQUATE and HSQC-1,n-ADEQUATE: enhanced methods for establishing adjacent and long-range 13C-13C connectivity networks. AB - 1H-13C GHSQC and GHMBC spectra are irrefutably among the most valuable 2D NMR experiments for the establishment of unknown chemical structures. However, the indeterminate nature of the length of the long-range coupling(s) observed via the (n)J(CH)-optimized delay of the GHMBC experiment can complicate the interpretation of the data when dealing with novel chemical structures. A priori there is no way to differentiate 2J(CH) from (n)J(CH) correlations, where n >= 3. Access to high-field spectrometers with cryogenic NMR probes brings 1,1- and 1,n ADEQUATE experiments into range for modest samples. Subjecting ADEQUATE spectra to covariance processing with high sensitivity experiments such as multiplicity edited GHSQC affords a diagonally symmetric 13C-13C correlation spectrum in which correlation data are observed with the apparent sensitivity of the GHSQC spectrum. HSQC-1,1-ADEQUATE covariance spectra derived by co-processing of GHSQC and 1,1-ADEQUATE spectra allow the carbon skeleton of molecules to be conveniently traced. HSQC-1,n-ADEQUATE spectra provide enhanced access to correlations equivalent to 4J(CH) correlations in a GHMBC spectrum. When these data are used to supplement GHMBC data, a powerfully synergistic set of heteronuclear correlations are available. The methods discussed are illustrated using retrorsine (1) as a model compound. PMID- 22054074 TI - TO901317 regulating apolipoprotein M expression mediates via the farnesoid X receptor pathway in Caco-2 cells. AB - BACKGROUND: Apolipoprotein M (apoM) may have potential antiatherosclerotic properties. It has been reported that apoM expression could be regulated by many intracellar and extracellar factors. In the present study we further investigated regulation of apoM expression in Caco-2 cells stimulated by a liver X receptor (LXR) agonist, TO901317. MATERIALS AND METHODS: Caco-2 cells were cultured in the presence of either TO901317, farnesoid X receptor (FXR) antagonist guggulsterone or TO901317 together with guggulsterone at different concentrations for 24 hrs. The mRNA levels of ATP-binding cassette transporter A1 (ABCA1), apoA1, apoM, liver receptor homologue-1 (LRH-1) and short heterodimer partner 1 (SHP1) were determined by real-time RT-PCR. RESULTS: When Caco-2 cell cultured with TO901317 alone, the mRNA levels of ABCA1, apoA1, apoM, LRH-1 and SHP1 were significantly increased with dose-dependent manners (p < 0.05), whereas when the cells cultured with guggulsterone alone, the mRNA levels of apoM, SHP1 and LRH-1 (p < 0.05) were strongly inhibited. Moreover, guggulsterone could abolish the TO901317 enhanced mRNA levels of apoA1 apoM, SHP1 and LRH-1. CONCLUSION: The present study demonstrated that LXR agonist TO901317 induced apoM expression in Caco-2 cells might be mediated via the LXR/FXR pathway. PMID- 22054076 TI - Palladium-catalyzed C-C bond formation of arylhydrazines with olefins via carbon nitrogen bond cleavage. AB - The unactivated carbon-nitrogen bond of various aryl hydrazines was cleaved under very mild conditions by Pd(0) with the assistance of Pd(II). The in situ generated aryl palladium complex readily takes part in the C-C bond formation with olefins. This study offered a new mode of C-Pd bond formation, which will spur the development of palladium-catalyzed cross-coupling in the future. PMID- 22054080 TI - Multidimensional Raman spectroscopic signatures as a tool for forensic identification of body fluid traces: a review. AB - The analysis of body fluid traces during forensic investigations is a critical step in determining the key details of a crime. Several confirmatory and presumptive biochemical tests are currently utilized. However, these tests are all destructive, and no single method can be used to analyze all body fluids. This review outlines recent progress in the development of a novel universal approach for the nondestructive, confirmatory identification of body fluid traces using Raman spectroscopy. The method is based on the use of multidimensional spectroscopic signatures of body fluids and accounts for the intrinsic heterogeneity of dry traces and donor variation. The results presented here demonstrate that Raman spectroscopy has potential for identifying traces of semen, blood, saliva, sweat, and vaginal fluid with high confidence. PMID- 22054077 TI - HIV-1 predisposed to acquiring resistance to maraviroc (MVC) and other CCR5 antagonists in vitro has an inherent, low-level ability to utilize MVC-bound CCR5 for entry. AB - BACKGROUND: Maraviroc (MVC) and other CCR5 antagonists are HIV-1 entry inhibitors that bind to- and alter the conformation of CCR5, such that CCR5 is no longer recognized by the viral gp120 envelope (Env) glycoproteins. Resistance to CCR5 antagonists results from HIV-1 Env acquiring the ability to utilize the drug bound conformation of CCR5. Selecting for HIV-1 resistance to CCR5-antagonists in vitro is relatively difficult. However, the CCR5-using CC1/85 strain appears to be uniquely predisposed to acquiring resistance to several CCR5 antagonists in vitro including MVC, vicriviroc and AD101. FINDINGS: Here, we show that Env derived from the parental CC1/85 strain is inherently capable of a low affinity interaction with MVC-bound CCR5. However, this phenotype was only revealed in 293 Affinofile cells and NP2-CD4/CCR5 cells that express very high levels of CCR5, and was masked in TZM-bl, JC53 and U87-CD4/CCR5 cells as well as PBMC, which express comparatively lower levels of CCR5 and which are more commonly used to detect resistance to CCR5 antagonists. CONCLUSIONS: Env derived from the CC1/85 strain of HIV-1 is inherently capable of a low-affinity interaction with MVC bound CCR5, which helps explain the relative ease in which CC1/85 can acquire resistance to CCR5 antagonists in vitro. The detection of similar phenotypes in patients may identify those who could be at higher risk of virological failure on MVC. PMID- 22054081 TI - High-pressure total internal reflection fluorescence apparatus. AB - Important interfacial processes in disciplines ranging from medicine to the separations sciences occur over a wide range of pressures, temperatures, and time scales. In this paper we report a new high-pressure total internal reflection fluorescence (HP-TIRF) apparatus that allows rapid fluorescence measurements of sub-monolayers in contact with liquids and supercritical fluids between 293 K and 353 K and up to 250 bar with picosecond time resolution. We use the HP-TIRF system to study the in-plane rotational reorientation dynamics of the fluorescent probe BODIPY 494/503 (C(2v) symmetry) covalently attached to silica surfaces that have been silanized with n-propyltrimethoxysilane (C(3)-TMOS) or 3,3,3 trifluoropropyltrimethoxysilane (CF(3)-TMOS) when the interface is subjected to pure supercritical carbon dioxide (scCO(2)). The in-plane BODIPY 494/503 rotational reorientation dynamics are assessed by using the Debye-Stokes-Einstein expression. As the scCO(2) density increases the local microviscosity surrounding the tethered BODIPY 494/503 molecule decreases. The terminal group (CH(3) versus CF(3)) within the silane monolayer governs the onset and absolute magnitude of the observed viscosity changes. The results are explained in terms of the wellknown solubility of fluorine-containing species in scCO(2). PMID- 22054082 TI - Fluorescence excitation-emission matrix (EEM) spectroscopy for rapid identification and quality evaluation of cell culture media components. AB - The application of fluorescence excitation-emission matrix (EEM) spectroscopy to the quantitative analysis of complex, aqueous solutions of cell culture media components was investigated. These components, yeastolate, phytone, recombinant human insulin, eRDF basal medium, and four different chemically defined (CD) media, are used for the formulation of basal and feed media employed in the production of recombinant proteins using a Chinese Hamster Ovary (CHO) cell based process. The comprehensive analysis (either identification or quality assessment) of these materials using chromatographic methods is time consuming and expensive and is not suitable for high-throughput quality control. The use of EEM in conjunction with multiway chemometric methods provided a rapid, nondestructive analytical method suitable for the screening of large numbers of samples. Here we used multiway robust principal component analysis (MROBPCA) in conjunction with n-way partial least squares discriminant analysis (NPLS-DA) to develop a robust routine for both the identification and quality evaluation of these important cell culture materials. These methods are applicable to a wide range of complex mixtures because they do not rely on any predetermined compositional or property information, thus making them potentially very useful for sample handling, tracking, and quality assessment in biopharmaceutical industries. PMID- 22054083 TI - Interaction of bisphenol A with bovine hemoglobin using spectroscopic and molecular modeling methods. AB - The interaction of bisphenol A with bovine hemoglobin (BHb) under physiological conditions was investigated by using fluorescence, ultraviolet-visible (UV-Vis) absorption, circular dichroism (CD), and molecular modeling. The experimental results showed that BPA can bind with BHb to form a complex. The binding constant Ka and the number of binding sites n were calculated to be 1.49 * 10(5) L mol(-1) and 1, respectively. Molecular modeling study revealed that BPA bound into BHb central cavity, and the binding mode of BPA-BHb complex could be hydrogen bonding. The UV-Vis absorption and CD spectra indicated that the secondary structure of BHb was altered, which may affect physiological functions of hemoglobin. This work is helpful for clarifying the molecular toxic mechanism of BPA in vivo. PMID- 22054084 TI - Sum frequency generation microscopy study of cellulose fibers. AB - Sum frequency generation (SFG) microscopy images of cotton cellulose fibers were observed at the infrared wavenumber of ~ 2945 cm(-1) and with a spatial resolution of 2 MUm. Domains of different cellulose microfibril bunches were observed and they showed different second-order nonlinear responses. The intensity of the peak of the asymmetric CH(2) stretching mode at 2945 cm(-1) depended strongly on the orientation of the electric fields of the incident visible and infrared light with respect to the cellulose fiber axis. The second order nonlinear susceptibility arising from the chirality in the cellulose structure was found to be dominant. The SFG of the cross section of the cellulose fiber was relatively weak and showed a different spectrum from that measured from the side of the fiber axis. PMID- 22054085 TI - A compact diode laser cavity ring-down spectrometer for atmospheric measurements of NO3 and N2O5 with automated zeroing and calibration. AB - A compact rack-mounted cavity ring-down spectrometer (CRDS) for simultaneous measurements of the nocturnal nitrogen oxides NO(3) and N(2)O(5) in ambient air is described. The instrument uses a red diode laser to quantify mixing ratios of NO(3) (at its absorption maximum at 662 nm) and of N(2)O(5) following its thermal dissociation to NO(3) in a second detection channel. The spectrometer is equipped with an automated zeroing and calibration setup to determine effective NO(3) absorption cross-sections and NO(3) and N(2)O(5) inlet transmission efficiencies. The instrument response was calibrated using simultaneous measurements of NO(2), generated by thermal dissociation of N(2)O(5) and/or by titration of NO(3) with excess NO, using blue diode laser CRDS at 405 nm. When measuring ambient air, the (2sigma, 10 s) precision of the red diode CRDS varied between 5 and 8 parts-per-trillion by volume (pptv), which sufficed to quantify N(2)O(5) concentrations under moderately polluted conditions. Sample N(2)O(5) measurements made on a rooftop on the University of Calgary campus in August 2010 are presented. A maximum N(2)O(5) mixing ratio of 130 pptv was observed, corresponding to a steady-state lifetime of less than 50 min. The NO(3) mixing ratios were below the detection limit, consistent with their predicted values based on equilibrium calculations. During the measurement period, the instrument response for N(2)O(5) was 70% of the theoretical maximum, rationalized by a slight mismatch of the laser diode output with the NO(3) absorption line and a N(2)O(5) inlet transmission efficiency less than unity. Advantages and limitations of the instrument's compact design are discussed. PMID- 22054086 TI - Near-infrared hollow waveguide gas sensors. AB - The development of a hollow core waveguide (HWG) gas sensor in combination with a fast and compact near-infrared (NIR) spectrometer is presented. The spectrometer operates in the spectral range of 1200-1400 nm and may thus be applied for the detection of gas-phase analytes providing NIR absorptions in that spectral window such as, e.g., methane. Since mid-infrared spectroscopy in combination with HWGs has already been successfully demonstrated for probing hydrocarbons in the gas phase, the present study investigates the achievable sensitivity in the NIR spectral regime. Methane has been selected as an exemplary analyte due to the fact that it shows strong absorption features in the mid-infrared (mid-IR) fingerprint area, but also overtone bands in the NIR. Since the HWG simultaneously serves as a miniaturized absorption gas cell and as an optical waveguide for NIR radiation, a compact yet optical and cost-efficient sensor device was established providing an interesting alternative in target sensing for mid-IR devices. The achieved limit of detection (LOD) was 5.7% (vol./vol.) methane for a 9.5 cm long HWG, 1.6% (vol./vol.) methane for a 39.1 cm long HWG, and 1.3% (vol./vol.) methane for a setup using a 77.4 cm long HWG, which provides the most practical HWG dimensions among the three investigated setups. Limit of quantitation (LOQ) values were calculated at 20.1% (vol./vol.) methane, 8.7% (vol./vol.) methane, and 5.6% (vol./vol.) methane, respectively. PMID- 22054087 TI - Sensitivity enhancement in near-field photothermal-lens detection in capillary electrophoresis using laser-induced online precipitation. AB - This paper reports simultaneous photoinduced precipitation-based online preconcentration of target analytes at the inner walls in capillary zone electrophoresis (CZE) and surface-enhanced near-field crossed-beam photothermal lens detection of the preconcentrated analytes. A simple technique using online readjustment of the optical scheme of the thermal-lens detector in the course of the separation for gaining optimum sensitivity for both water-soluble and precipitated analytes is proposed. It provides a considerable decrease in the limits of detection (LOD) with good concordance with the previously developed theoretical approach to this combination (D. A. Nedosekin, W. Faubel, M. A. Proskurnin, and U. Pyell, Talanta, 78, 682-690 (2009)). As a result, an enhancement of more than an order of magnitude in the limit of detection of the photoactive 4-aminoazobenzene compared to conventional thermal-lens detection in CZE is achieved while retaining very good sensitivity for unabsorbed analyte (Mordant Yellow 7). The application of the thermal-lens detector to the investigation of laser-induced reactions in flow in capillaries is discussed. PMID- 22054088 TI - Identification of inorganic pigments used in porcelain cards based on fusing Raman and X-ray fluorescence (XRF) data. AB - Raman spectroscopy and X-ray fluorescence (XRF) spectroscopy are often used as complementary techniques that are well suited for the analysis of art objects because both techniques are fast, sensitive, and noninvasive and measurements can take place in situ. In most of these studies, both techniques are used separately, in the sense that the spectra are evaluated independently and single conclusions are obtained, considering both results. This paper presents a data fusion procedure for Raman and XRF data for the characterization of pigments used in porcelain cards. For the classification of the analyzed points of the porcelain cards principal component analysis (PCA) was used. A first attempt was made to develop a new procedure for the identification of the pigments using a database containing the fused Raman-XRF data of 24 reference pigments. The results show that the classification based on the fused Raman-XRF data is significantly better than the classifications based on the Raman data or the XRF data separately. PMID- 22054089 TI - Characterizing the structure of pharmaceutical granules obtained by wet granulation with varying amounts of water via Raman chemical imaging. AB - A pharmaceutical formulation containing metformin hydrochloride (MET), hydroxypropyl cellulose (HPC), and microcrystalline cellulose (MCC) was wet granulated with varying amounts of water and the structure of the obtained granules was characterized by Raman chemical mapping. Univariate Raman mapping was found to be satisfactory for producing the images of the two components of interest (HPC and MCC). In addition to the images, the average Raman spectra from the maps as well as the micro-Raman spectra from the hot pixels were analyzed. HPC is found to strongly respond to the addition of water, with its domain dissipating and Raman bands becoming weaker as the water addition increases. MCC is also responsive to water, reacting similarly to HPC but to a much smaller extent and only for the largest amounts of water. Granules made with increasing water content also have improved tabletting properties and flow. PMID- 22054090 TI - An improved algorithm to remove cosmic spikes in Raman spectra for online monitoring. AB - Raman spectral analysis integrated with multivariate calibration is a fast and effective solution to monitor chemical product properties. However, Raman instruments utilizing charge-coupled device (CCD) detectors suffer from occasional spikes caused by cosmic rays. Cosmic spikes can disturb or even destroy the meaningful chemical information expressed by normal Raman spectra. In online monitoring, some cosmic spikes have intensity and bandwidth similar to normal Raman peaks of chemical components when a low resolution and cost effective Raman instrument is used. Moreover, the online Raman spectra always contain variations of strong Raman peaks and fluorescence. Current spike-removal methods seem to have difficulty detecting and recovering cosmic spikes in these online Raman spectra. Therefore, an improved algorithm is proposed. In this algorithm, a new scheme composed of intensity identification and local moving window correlation analysis is introduced for cosmic spike detection; intensity identification based on derivative spectra and local linear fitting approximation are used for the recovery of cosmic spikes. The algorithm is proved to be simple and effective and has been applied in an online Raman instrument installed at a continuous catalytic reforming unit in a refinery. PMID- 22054091 TI - Temperature effects on the optical path length of infrared liquid transmission cells. AB - Infrared (IR) spectroscopy is widely used for studies of temperature-dependent properties of liquids and solutions, such as thermal denaturation of proteins and other molecules of biological interest. The variation of the spectroscopic signals with temperature can be affected by the changes in the optical path length due to the thermal expansion of the components of the sample cell. In this report we investigate the temperature dependence of the optical path length for a liquid IR sample cell of a design typical for aqueous solution experiments. The path lengths were measured from the interference fringes, both in dry cells and with cells partially filled with water. We found that the optical path length variations are significant, on the order of several percent within the temperature range used (0-87 degrees C). Several commercially available spacers (Teflon, mylar, and lead) and gaskets (Teflon, lead, silicone rubber, Viton, and neoprene) were tested to find materials with either the smallest or most reproducible effect. Teflon, due to its phase transition (known as the "knee point") near room temperature, leads to abrupt changes in path length when used as either spacer or gasket component. On the other hand, Teflon is preferred for its inertness, while several of the other tested materials, most notably lead, are not practically usable due to adhesion to the cell windows upon heating and contact with the aqueous sample. The combination that yielded the most reproducible results, with minimal complications due to adhesion, was Teflon spacer with neoprene gaskets. The implications of the optical path length changes for the temperature-dependent IR experiments and their possible corrections are discussed. PMID- 22054092 TI - Effect of sample thickness on the extracted near-infrared bulk optical properties of Bacillus subtilis in liquid culture. AB - In order to determine the bulk optical properties of a Bacillus subtilis culture during growth phase we investigated the effect of sample thickness on measurements taken with different measurement configurations, namely total diffuse reflectance and total diffuse transmittance. The bulk optical properties were extracted by inverting the measurements using the radiative transfer theory. While the relationship between reflectance and biomass changes with sample thickness and the intensity (absorbance) levels vary significantly for both reflectance and transmittance measurements, the extracted optical properties show consistent behavior in terms of both the relationship with biomass and magnitude. This observation indicates the potential of bulk optical properties for building models that could be more easily transferable compared to those built using raw measurements. PMID- 22054093 TI - Laser phosphoroscope and applications to room-temperature phosphorescence. AB - A simple phosphoroscope with no moving parts is described. In one scan the total luminescence, the long-lived phosphorescence, and the short-lived fluorescence can be determined. A 50% duty cycle excitation from a diode laser is used to excite the sample, and from the digitized waveform the phosphorescence is extracted from the off period, the total emission from the full cycle, and the fluorescence from the on period corrected for the phosphorescence contribution. The performance of the system is demonstrated using room-temperature phosphorescence of organic dyes in boric acid glasses, a multi-emissive boron polymer dye, and a europium chelate. PMID- 22054095 TI - Early events in the photochemistry of 1,2,3-thiadiazole studied by ultrafast time resolved UV-vis and IR spectroscopies. AB - Photochemistry of 4-methyl-5-carboethoxy-1,2,3-thiadiazole (MCT) in solution was studied at room temperature using UV-vis and IR transient absorption spectroscopies (lambda(ex) = 266 nm). Three deactivation pathways are discussed: thiirene formation, thioketene generation, and the internal conversion by repopulating MCT in the ground state. Ultrafast techniques show a very fast rise (<0.4 ps) of thiirene species in acetonitrile, possibly as a result of a rearrangement in the singlet excited state of MCT in concert with molecular nitrogen extrusion. The remarkable stability of thiirene in solution on a millisecond time scale is limited by the process of dimerization (thiirene thiirene, thiirene-thioketene). NMR analysis permitted identification of stable photoproducts as 1,3-dithietane, 1,3-dithiole, and thiophene derivatives. PMID- 22054094 TI - Differential pattern of glycogen accumulation after protein phosphatase 1 glycogen-targeting subunit PPP1R6 overexpression, compared to PPP1R3C and PPP1R3A, in skeletal muscle cells. AB - BACKGROUND: PPP1R6 is a protein phosphatase 1 glycogen-targeting subunit (PP1 GTS) abundant in skeletal muscle with an undefined metabolic control role. Here PPP1R6 effects on myotube glycogen metabolism, particle size and subcellular distribution are examined and compared with PPP1R3C/PTG and PPP1R3A/G(M). RESULTS: PPP1R6 overexpression activates glycogen synthase (GS), reduces its phosphorylation at Ser-641/0 and increases the extracted and cytochemically stained glycogen content, less than PTG but more than G(M). PPP1R6 does not change glycogen phosphorylase activity. All tested PP1-GTS-cells have more glycogen particles than controls as found by electron microscopy of myotube sections. Glycogen particle size is distributed for all cell-types in a continuous range, but PPP1R6 forms smaller particles (mean diameter 14.4 nm) than PTG (36.9 nm) and G(M) (28.3 nm) or those in control cells (29.2 nm). Both PPP1R6 and G(M)-derived glycogen particles are in cytosol associated with cellular structures; PTG-derived glycogen is found in membrane- and organelle-devoid cytosolic glycogen-rich areas; and glycogen particles are dispersed in the cytosol in control cells. A tagged PPP1R6 protein at the C-terminus with EGFP shows a diffuse cytosol pattern in glucose-replete and -depleted cells and a punctuate pattern surrounding the nucleus in glucose-depleted cells, which colocates with RFP tagged with the Golgi targeting domain of beta-1,4 galactosyltransferase, according to a computational prediction for PPP1R6 Golgi location. CONCLUSIONS: PPP1R6 exerts a powerful glycogenic effect in cultured muscle cells, more than G(M) and less than PTG. PPP1R6 protein translocates from a Golgi to cytosolic location in response to glucose. The molecular size and subcellular location of myotube glycogen particles is determined by the PPP1R6, PTG and G(M) scaffolding. PMID- 22054096 TI - One-stage laparoscopic-assisted resection of gastrojejunocolic fistula after gastrojejunostomy for duodenal ulcer: a case report. AB - INTRODUCTION: Gastrojejunocolic fistula is a rare condition after gastrojejunostomy. It was thought to be a late complication related to stomal ulcers as a result of inadequate gastrectomy or incomplete vagotomy. We report a case of gastrojejunocolic fistula after gastrojejunostomy for peptic ulcer treated with one-stage laparoscopic resection. CASE PRESENTATION: A 41-year-old Japanese man complained of diarrhea for 10 months, as well as severe weight loss and weakness. After admission, we immediately started intravenous hyperalimentation. On performing colonoscopy and barium swallow, gastrojejunocolic fistula was observed close to the gastrojejunostomy site leading to the transverse colon. After our patient's nutritional status had improved, one-stage surgical intervention was performed laparoscopically. After the operation, our patient recovered uneventfully and his body weight increased by 5 kg within three months. CONCLUSIONS: Modern management of gastrojejunocolic fistula is a one-stage resection because of the possibility of early recovery from malnutrition using parenteral nutritional methods. Today, laparoscopic one stage en bloc resection may be feasible for patients with gastrojejunocolic fistula due to the development of laparoscopic instruments and procedures. We describe the first case of gastrojejunocolic fistula treated laparoscopically by one-stage resection and review the literature. PMID- 22054097 TI - Dual-frequency electrowetting: application to drop evaporation gauging within a digital microsystem. AB - This paper addresses a method to estimate the size of a sessile drop and to measure its evaporation kinetics by making use of both Michelson interferometry and coplanar electrowetting. From a high-frequency electrowetting voltage, the contact angle of the sessile droplet is monitored to permanently obtain a half liquid sphere, thus complying perfectly with the drop evaporation theory based on a constant contact angle (Bexon, R.; Picknett, R. J. Colloid Interface Sci. 1977, 61, 336-350). Low-frequency modulation of the electrowetting actuation is also applied to cause droplet shape oscillations and capillary resonance. Interferometry allows us to measure a time-dependent capillary spectrum and, in particular, the shift in natural frequencies induced by drop evaporation. Consequently, diffusive kinetics of drop evaporation can be properly estimated, as demonstrated. Because of coplanar electrode configuration, our methodology can be integrated in open and covered microsystems, such as digital lab-on-a-chip devices. PMID- 22054098 TI - Salmonella-mediated tumor-targeting TRAIL gene therapy significantly suppresses melanoma growth in mouse model. AB - Attenuated Salmonella typhimurium (S. typhimurium) strains can selectively grow and express exogenous genes in tumors for targeted therapy. We engineered S. typhimurium strain VNP20009 to secrete tumor necrosis factor-related apoptosis inducing ligand (TRAIL) under the control of a hypoxia-induced nirB promoter and examined the efficacy of Salmonella-mediated targeted expression of TRAIL in mice bearing melanoma tumor and in TRAIL-resistant RM-1 tumor. We found that VNP preferentially accumulated in tumor tissues and the nirB promoter effectively drove targeted expression of TRAIL. Compared with recombinant TRAIL protein and VNP20009 combination therapy, VNP20009 expressing TRAIL significantly suppressed melanoma growth but failed to suppress RM-1 tumor growth. Furthermore, we confirmed that VNP20009 expressing TRAIL yielded its antitumor effect by inducing melanoma apoptosis. Our findings indicate that Salmonella-mediated tumor-targeted therapy with TRAIL could reduce tumor growth and extend host survival. PMID- 22054099 TI - Determination of cytochrome P450 enzymes involved in the metabolism of (-) terpinen-4-ol by human liver microsomes. AB - The in vitro metabolism of (-)-terpinen-4-ol was examined in human liver microsomes and recombinant enzymes. The biotransformation of (-)-terpinen-4-ol was investigated by gas chromatography-mass spectrometry. (-)-Terpinen-4-ol was found to be oxidized to (-)-(1S,2R,4R)-1,2-epoxy-p-menthan-4-ol, major metabolic product by human liver microsomal P450 enzymes. The formation of metabolites of ( )-terpinen-4-ol was determined by relative abundance of mass fragments and retention times on GC. CYP2A6 in human liver microsomes was a major enzyme involved in the oxidation of (-)-terpinen-4-ol by human liver microsomes, based on the following lines of evidence. First, of 11 recombinant human P450 enzymes tested, CYP2A6 had the highest activity for oxidation of (-)-terpinen-4-ol. Second, oxidation of (-)-terpinen-4-ol was inhibited by (+)-menthofuran. Finally, there was a good correlation between CYP2A6 maker activity and (-)-terpinen-4-ol oxidation activities in liver microsomes of 10 human samples. Kinetic analysis showed that the V(max)/K(m) values for (-)-(1S,2R,4R)-1,2-epoxy-p-menthan-4-ol catalysed by liver microsomes of human sample HH-18 was 2.49 MUL/min/nmol. Human recombinant CYP2A6 catalysed (-)-(1S,2R,4R)-1,2-epoxy-p-menthan-4-ol with V(max) values of 13.9 nmol/min/nmol P450 and apparent K(m) values of 91 MUM. PMID- 22054101 TI - Potential Co-prevalence of Plasmid-Mediated Quinolone Resistance Determinant qepA and 16S rRNA Methylase rmtB among E.coli Clinical Isolates from Alexandria- Egypt. AB - BACKGROUND: Fluoroquinolone-resistant Gram-negative pathogens have been increasingly reported from most regions of the world over the last decade. A new plasmid-mediated fluoroquinolone efflux pump gene (qepA) is known to be associated with the 16S rRNA methylase gene (rmtB) that confers resistance to aminoglycosides. AIM: To investigate the potential co-prevalence of qepA and rmtB genes in Escherichia coli (E. coli) clinical isolates collected from Egyptian medical facilities. MATERIAL AND METHODS: A total of 225 non-duplicate E. coli isolates were collected between 2008 and 2009 from two hospitals in Alexandria. Isolates were initially tested for their antibiotic susceptibility by disc diffusion method. Isolates exhibited quinolone and aminoglycosides co-resistance profile were screened for the presence of qepA and rmtB genes. The effect of efflux pump inhibitor, phenylarginine-beta-naphthylamide (PAbetaN) on the minimum inhibitory concentration (MIC) of ciprofloxacin, levofloxacin and gentamicin against these strains was tested and log activity index was calculated. Using checkerboard titration method, the combinations of gentamicin with ciprofloxacin against the strains harboring qepA and rmtB genes were tested and the fractional inhibitory concentrations (FIC) were calculated. RESULTS: Forty-five E. coli isolates exhibited quinolone and aminoglycosides co-resistance profile. Of them, two E. coli isolates were positive for qepA, and three harbored rmtB genes. No association between both genes was detected. The calculated log activity index revealed a reduction in MIC of the fluoroquinolones with PAbetaN but not of gentamicin. FIC calculated here for gentamicin/ciprofloxacin combinations reflected either antagonism or indifference against the strains harboring qepA and rmtB genes. CONCLUSION AND RECOMMENDATIONS: qepA as well as rmtB genes carrying E. coli strains could become a greater nosocomial infection problem with appropriate foci of selective pressure. Therefore, public health support for active surveillance for plasmid mediated fluoroquinolones, aminoglycosides resistance determinants among clinical E. coli isolates should be encouraged. In addition, the effect of efflux pumps needs to be considered in the design of future antibiotics as their synergistic role may pave the way to novel combination therapies that could be used against these strains. PMID- 22054102 TI - Comparative study on efficacy of different alcohol hand rubs and routine hand wash in a health-care setting, alexandria, egypt. AB - BACKGROUND: Antiseptic agents or plain soap and water are mainly used for hand hygiene in Egypt. The impact of hand hygiene depends not only on the regularity and thoroughness of the procedures used but also on the type of hand-washing agent selected. OBJECTIVES: To compare the efficacy of alcohol-based hand rubs versus traditional hand washing with soap and water in reducing hand contamination during routine patient care. MATERIAL AND METHODS: The study included 20 volunteered nurses in 3 intensive care units and the renal dialysis unit, in the Alexandria University Students' Hospital. A total of 200 samples were collected by direct finger-print of the dominant hand taken from all nurses before and after applying hand hygiene procedures. Three hand-rubs available in the Egyptian market (Brands A, B; alcohol-based liquid, and C; alcohol-based gel) were used and compared to a locally prepared hand-rubbing solution (D) and to hand washing with non-antiseptic soap and water (SW). RESULTS: Hand washing with non-antiseptic soap and water and all of the four used alcohol-based hand-rubs showed significant reduction of bacterial counts on the examined hands. The median percentage reductions were 99%, 94%, 77%, and 87% with brands A, B, C and D respectively and only 30% reduction with soap and water (x2: 23.023, p <0.001). CONCLUSIONS AND RECOMMENDATIONS: Alcohol-based hand rub is far more efficient than traditional hand washing, and more convenient and time saving. Locally prepared hand rub is comparable to readymade ones. It is recommended as a hand hygiene practice in critical areas, particularly when sink and running water are inaccessible. PMID- 22054103 TI - TUBEX Test Versus Widal Test In The Diagnosis Of Typhoid Fever In Kafr El Shekh, Egypt. AB - BACKGROUND: The value of the Widal test for the diagnosis of typhoid fever has been debated for as many years as it has been available. TUBEX test is a serological test which was stated to have the advantages of the Widal test without its controversies. The aim of this study was to evaluate TUBEX test versus the Widal test regarding sensitivity and specificity for the diagnosis of typhoid fever in an endemic area like Kafr El -Shekh, Egypt. MATERIALS AND METHODS: Serum samples were collected from typhoid (n=91) and febrile non-typhoid patients (n=25) and used to evaluate the performance of both Widal and TUBEX tests in diagnosis of typhoid fever using IgM anti-LPS ELISA as a reference test. RESULTS: TUBEX test had sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 74.6%, 75%, 74.7%, 89.2% and 58% respectively. Widal test had higher results. CONCLUSION AND RECOMMENDATION: TUBEX test results are not superior to Widal test. TUBEX has a very serious shortcoming regarding its color scoring system. We do not recommend the use of TUBEX test for diagnosis of typhoid fever in Egypt as Widal test which is the test commonly used in diagnosis gave better performance. PMID- 22054104 TI - Transmission of Administered Amoxicillin Drug Residues from Laying Chicken to their Commercial Eggs. AB - BACKGROUND: Antimicrobial agents in food producing animals are a very important public health issue. They are routinely added to animal feed at sub-therapeutic levels for their growth promoting properties. This practice, however, carries many disadvantages, such as the stimulation of microbial resistance to antibiotics. AIM: This study was carried out to determine administered Amoxicillin residues in laying chickens and in their commercial eggs, and the effect of cooking and storage condition on Amoxicillin residues in their eggs. MATERIAL AND METHODS: A total of 50 terminal faeces were collected from laying hens in addition, a total of 215 commercial egg samples were randomly selected from the farm treated with Amoxicillin. Microbiological agar diffusion method was used. RESULTS: the withdrawal time of Amoxicillin was 7 days. Its residues were detected in both egg yolks and egg whites for 6 successive days after the last drug administration. In addition, Amoxicillin residues remained until the 7th day from drug administration in eggs stored at room temperature, and at 4 degrees C. Amoxicillin residue was not affected after boiling eggs for 10 minutes. CONCLUSIONS AND RECOMMENDATIONS: eggs should not be distributed to markets until the end of the drug's withdrawal period. It is also recommended to observe the withdrawal period of drugs before poultry slaughter or table egg distribution to avoid antimicrobial resistance and to inform both owners and consumers about the risks of antibiotic residues in egg contents. PMID- 22054105 TI - Infants' fussiness on the breast; a window to salvage breastfeeding before breast rejection. AB - BACKGROUND: Infants' fussiness on the breast is a common lactation problem that can proceed to complete breastfeeding refusal if not professionally handled. AIM OF WORK: To study the factors associated with infants' fussiness while breastfeeding and the effect of proper lactation counselling on the breastfeeding outcome. SUBJECTS AND METHODS: This is an interventional study conducted in the breastfeeding clinic of the Cairo university children's hospital. Forty-six fussy infants were recruited. Personal interview together with assessment of the act of breastfeeding were done for each mother-infant dyad. The mothers' milk letdown was assessed by manual expression. Intervention was done by proper lactation counselling, guided by the WHO/UNICEF breastfeeding counselling training course. RESULTS: 28 (61%) of the mothers had forceful milk letdown versus 9 (19.5%) having average letdown and 9 (19.5%) having inhibited letdown (p<0.01). 13 infants were using pacifiers, which was stopped in 10 of them (p=0.01), 8 infants received formula and 5 mothers were smokers and all couldn't stop smoking. Upon counselling, 37 infants continued breastfeeding without fussiness and 9 stopped it (p<0.01). The greatest success was accomplished in mothers having forceful letdown (p=0.0001) and average letdown (p=0.01), rather than those having inhibited letdown (p=0.57). 19 of the 37 mothers having acceptable let down were presenting with perceived low milk supply and only 3 remained unconvinced (p<0.01). 46.2% of pacifier users, 100% of formula users and 80% of infants of smoker mothers quitted breastfeeding. Conclusion & Recommendations: Forceful milk letdown is commonly associated with fussiness on the breast with good outcome if properly managed. Inhibited letdown, smoking, bottle-feeding and pacifier use are associated with breastfeeding rejection. Low milk supply is a commonly "perceived" problem that should be properly assessed and handled by lactation consultants. Medical professionals should be oriented about the common breastfeeding problems, their prophylaxis and management and their role should go beyond just "motivating" mothers to breastfeed without practical guidance. PMID- 22054106 TI - Review on health effects related to mobile phones (part I: introduction and methodology). AB - OBJECTIVE: The objective of this study is to review the recent literature on the health effects of exposure to mobile phones. METHODS: The literature published in the last 10 years (2000-2010) has been reviewed. Those published in 2011 will be included in the updated review (part 2). Searches were made electronically through various search engines and health-related databases, and manually through journals, reports, and conference proceedings. The references used in the introduction of part 1 were mainly WHO reports, textbooks, and non serial publications. RESULTS: Search strategies identified a total of 772 references, with 85 finally being included in the results for 2000-2010. Nearly all types of studies were included in the review (experimental in vitro, in vivo, human provocation studies, epidemiological studies and review articles). The reported effects associated with exposure to mobile phones did not show a consistent pattern. Studies on exposure in children were very few. CONCLUSIONS: In spite of the abundance of publications on the effects of mobile phones, yet, at present, there is no consistency in the scientific evidence regarding their adverse health effects. Methodological problems are mostly behind these variation. However, strong and consistent evidence was revealed by review studies including meta analysis which indicated that driving performance was significantly impacted when drivers were concurrently talking on a mobile phone, whether hand-held or hands free. Continued research is recommended to address specific areas of concern, including health effects in children using mobile phones, and the relation between long-term low-level exposure to mobile phones and cancer. PMID- 22054108 TI - Effects of epidural capsaicin on nociceptive threshold and neurological functions in rabbits. AB - Capsaicin, as a principle active component of Chili peppers, is popularly consumed by many people around the world. Whether capsaicin-induced neuropathy alters the function of sensory neurons is still unknown. OBJECTIVE: The objectives of this study were to determine the effects of epidural capsaicin on nociceptive threshold and neurological functions in a rabbit model. DESIGN: An intrathecal injection system was set up using a rabbit model. Rabbits were treated with capsaicin at doses of 0.04, 0.10, and 0.20 mg/kg once. The changes in neurological functions and morphology of the spinal cord and spinal nerve roots were determined within 24 hours. Changes in the nociceptive threshold in the hind limbs of the rabbits were observed for 30 days. METHODS: Capsaicin's effect on the changing neurological functions was evaluated by the neurological functional scores. The structural changes of spinal cord and spinal nerve roots were observed by hematoxylin and eosin staining and transmission electron microscopy. The nociceptive threshold changes in the rabbits were measured by the responding time for pain induced by a thermostimulation. RESULTS: The results showed that capsaicin reversed changes in the neurological function of rabbit hindlimbs. In the 0.10 and 0.20 mg/kg groups, structural abnormalities were found in the rabbit's spinal nerves. Capsaicin also significantly increased the pain threshold in rabbits when compared with the control group (P < 0.05 or P < 0.01). The maximum values of pain threshold were found in the 0.10 mg/kg capsaicin group after 3 days of capsaicin treatment. CONCLUSION: With the exception of a potential toxicity, capsaicin may be a potential candidate agent for providing pain relief of both neuropathic and nociceptive conditions. PMID- 22054109 TI - Universalism, universal design and equitable access to the built environment. AB - PURPOSE: The concept of universal design (UD) has acquired global significance and become orthodoxy of what is presented as the very best of design practice. This is despite limited evaluation of the theoretical content of the concept. This article seeks to redress this shortfall in knowledge by providing a critique of the theoretical and conceptual components that underpin the principles of universal design. METHOD: Commentary. RESULTS: The content of UD appears to be reductive and functionalist, with an appeal to discourses of technical flexibility, or the notion that the problems confronting disabled people by poorly designed built environments may be redressed by recourse to technical and management solutions. UD is characterized by its advocation of the marketization of access as the primary means to ensure the accessibility of products, including the built environment. This has the potential to reduce the "right to access" to a right to be exercised through a market presence or transaction. There is also lack of clarity about what advocates of UD understand universalism to be, as illustrated by evidence of some ambivalence towards specialist or particular design solutions. CONCLUSIONS: UD provides a useful, yet partial, understanding of the interrelationships between disability and design that may limit how far inequalities of access to the built environment can be overcome. PMID- 22054110 TI - Early recurrence of atrial tachyarrhythmias following radiofrequency catheter ablation of atrial fibrillation. AB - The use of blanking periods, the immediate period postablation during which transient tachyarrhythmia episodes are not considered recurrences, has been predicated on the assumption that not all early recurrences of atrial tachyarrhythmias (ERAT) will lead to later recurrences and, as such, does not necessarily represent treatment failure. While ERAT can be expected to occur in approximately 38% of patients within the first 3 months of atrial fibrillation (AF) ablation, only half of these patients will manifest later recurrences. Clinical features related to the patient's history of AF, the index ablation procedure, and particularities of the ERAT can help identify patients at higher risk of later recurrence in whom aggressive attempts to control rhythm, including early cardioversion and reintervention, may be justified. PMID- 22054111 TI - Molecular analysis of hepatitis B virus (HBV) in an HIV co-infected patient with reactivation of occult HBV infection following discontinuation of lamivudine including antiretroviral therapy. AB - BACKGROUND: Occult hepatitis B virus (HBV) infection (OBI) is characterized by HBV DNA persistence even though the pattern of serological markers indicates an otherwise resolved HBV infection. Although OBI is usually clinically silent, immunocompromised patients may experience reactivation of the liver disease. CASE PRESENTATION: We report the case of an individual with human immunodeficiency virus (HIV) infection and anti-HBV core antibody positivity, who experienced severe HBV reactivation after discontinuation of lamivudine-including antiretroviral therapy (ART). HBV sequencing analysis showed a hepatitis B surface antigen escape mutant whose presence in an earlier sample excluded reinfection. Molecular sequencing showed some differences between two isolates collected at a 9-year interval, indicating HBV evolution. Resumption of ART containing an emtricitabine/tenofovir combination allowed control of plasma HBV DNA, which fell to undetectable levels. CONCLUSION: This case stresses the ability of HBV to evolve continuously, even during occult infection, and the effectiveness of ART in controlling OBI reactivation in HIV-infected individuals. PMID- 22054112 TI - The acute effects of a pulse-containing meal on glycaemic responses and measures of satiety and satiation within and at a later meal. AB - Pulses are low glycaemic foods; however, their effect on satiation is unknown. The objective was to determine the effects of an ad libitum pulse meal on food intake (FI), appetite and blood glucose (BG) before and after a test meal (4 h later) and on FI at the test meal. Males (n 24, 22.8 kg/m2) received one of four treatments or control. The pulse treatments contained pasta and tomato sauce and 44 % of energy from: (1) chickpeas, (2) lentils, (3) navy beans or (4) yellow peas. The control was pasta and tomato sauce (pasta and sauce). FI (satiation) was measured at the treatment meal (0-20 min) and at an ad libitum pizza meal 4 h later. BG and appetite were measured from 0 to 340 min. At the treatment meal, lentils led to lower FI compared to chickpeas and pasta and sauce, whereas navy beans led to lower FI compared to chickpeas. Also, lentils led to lower cumulative FI compared to pasta and sauce. All pulses led to lower BG peak and cumulative area under the curve (AUC; 0-340 min); however, only chickpeas, lentils and navy beans reduced pre-pizza meal BG AUC (0-260 min) relative to pasta and sauce. Chickpeas led to lower post-pizza meal BG AUC (260-340 min) compared to navy beans and yellow peas. Consumption of pulses in a high-glycaemic meal contributes to earlier satiation, lower BG following the meal and after a later meal, but these effects are specific to pulse type and cannot be explained by their glycaemic properties alone. PMID- 22054115 TI - Low 5-min Apgar score in moderately preterm infants; association with subsequent death and cerebral palsy: a register based Danish national study. PMID- 22054114 TI - Interfacial orientation and secondary structure change in tachyplesin I: molecular dynamics and sum frequency generation spectroscopy studies. AB - Recent advances in the collection and interpretation of surface-sensitive vibrational spectroscopic measurements have made it possible to study the orientation of peptides and proteins in situ in a biologically relevant environment. However, interpretation of sum frequency generation (SFG) and attenuated total reflectance Fourier transform infrared (ATR-FTIR) vibrational spectroscopy is hindered by the fact that orientation cannot be inferred without some prior knowledge of the protein structure. In this work, molecular dynamics simulations were used to study the interfacial orientation and structural deformation of the short beta-sheet peptide tachyplesin I at the polystyrene/water interface. By combining these results with ATR-FTIR and SFG measurements, reasonable agreement was found with the simulation results, suggesting that tachyplesin I lies parallel to the surface, although the simulation results imply a broader distribution of peptide twist angles than could be characterized using available experimental measurements. The interfacial structure was found to be deformable even when disulfide bonds were preserved, and these local deviations from a purely extended beta-sheet conformation may be of importance to future developments in the interpretation of SFG and ATR-FTIR spectra. PMID- 22054116 TI - The pharmacology of new antiepileptic drugs: does a novel mechanism of action really matter? PMID- 22054117 TI - The hippocampus, neurotrophic factors and depression: possible implications for the pharmacotherapy of depression. AB - Depression is a prevalent, highly debilitating mental disorder affecting up to 15% of the population at least once in their lifetime, with huge costs for society. Neurobiological mechanisms of depression are still not well known, although there is consensus about interplay between genetic and environmental factors. Antidepressant medications are frequently used in depression, but at least 50% of patients are poor responders, even to more recently discovered medications. Furthermore, clinical response only occurs following weeks to months of treatment and only chronic treatment is effective, suggesting that actions beyond the rapidly occurring effect of enhancing monoaminergic systems, such as adaptation of these systems, are responsible for the effects of antidepressants. Recent studies indicate that an impairment of synaptic plasticity (neurogenesis, axon branching, dendritogenesis and synaptogenesis) in specific areas of the CNS, particularly the hippocampus, may be a core factor in the pathophysiology of depression. The abnormal neural plasticity may be related to alterations in the levels of neurotrophic factors, namely brain-derived neurotrophic factor (BDNF), which play a central role in plasticity. As BDNF is repressed by stress, epigenetic regulation of the BDNF gene may play an important role in depression. The hippocampus is smaller in depressed patients, although it is unclear whether smaller size is a consequence of depression or a pre-existing, vulnerability marker for depression. Environmental stressors triggering activation of the hypothalamic-pituitary-adrenal axis cause the brain to be exposed to corticosteroids, affecting neurobehavioural functions with a strong downregulation of hippocampal neurogenesis, and are a major risk factor for depression. Antidepressant treatment increases BDNF levels, stimulates neurogenesis and reverses the inhibitory effects of stress, but this effect is evident only after 3-4 weeks of administration, the time course for maturation of new neurons. The ablation of hippocampal neurogenesis blocks the behavioural effects of antidepressants in animal models. The above findings suggest new possible targets for the pharmacotherapy of depression such as neurotrophic factors, their receptors and related intracellular signalling cascades; agents counteracting the effects of stress on hippocampal neurogenesis (including antagonists of corticosteroids, inflammatory cytokines and their receptors); and agents facilitating the activation of gene expression and increasing the transcription of neurotrophins in the brain. PMID- 22054120 TI - Evaluation of serum levels of chemokines during interferon-beta treatment in multiple sclerosis patients: a 1-year, observational cohort study. AB - BACKGROUND: The molecules that provide access to activated T cells in the CNS, including chemokines, have been considered to be a crucial step in the pathogenesis of multiple sclerosis (MS). AIMS: In this study, we investigated serial serum chemokine levels in patients with relapsing-remitting MS over 1 year and the association of these chemokine levels with treatment regimens, lesions on MRI and patients' characteristics. METHODS: Serum CXCL9, CXCL10, CCL2, CCL4 and CCL5 levels were evaluated using ELISA every 2 months for a year in 28 healthy controls and 28 MS patients during their treatment with interferon (IFN)-beta. Patients underwent MRI and were evaluated using the Expanded Disability Status Scale (EDSS) at the first and final evaluations. RESULTS: CXCL10 serum levels were higher in MS patients compared with controls, were positively correlated with T2 lesions on MRI and were slightly increased during relapses. Treatment with IFNbeta-1a or IFNbeta-1b was associated with increased CXCL10 levels when evaluated more than 36 hours after subcutaneous injection. The CXCL9 levels were higher after MS relapse. There was significant variability in CCL4 and CCL5 levels in the serial evaluations, associated with gender and treatment. CCL2 levels were higher in treated MS patients than healthy controls, particularly among those patients with a stable form of the disease. CONCLUSION: Serum is a feasible resource for searching for an immunological marker in MS. Peripheral chemokine levels correlated in different ways with IFNbeta therapy and with disease and patient characteristics. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN45526724. PMID- 22054121 TI - Needle-free subcutaneous sumatriptan: in the acute treatment of migraine attacks or cluster headache episodes. AB - A needle-free device for delivering a 6 mg fixed dose of sumatriptan into subcutaneous tissues has been developed and approved for the acute treatment of migraine and cluster headache in the US and some EU countries. In a pivotal registration study in healthy adult volunteers, a single dose of needle-free subcutaneous sumatriptan 6 mg demonstrated bioequivalence to a single dose of traditional, needle-based subcutaneous sumatriptan 6 mg when delivered into the abdomen or the thigh, but not the arm. In a noncomparative, multicentre, phase IV study, the administration of (one or two doses of) needle-free subcutaneous sumatriptan 6 mg consistently provided rapid and sustained relief from migraine pain and associated symptoms during the treatment of up to four migraine attacks over a period of up to 60 days among current triptan users. Moreover, the use of needle-free subcutaneous sumatriptan was associated with a significant improvement in treatment satisfaction in these patients who were less than 'very satisfied' with their usual symptomatic therapy. Needle-free subcutaneous sumatriptan was generally well tolerated in the phase IV study. Although the overall adverse event profile of the needle-free delivery system was similar to that previously reported for the needle-based delivery system, it was associated with a numerically higher incidence of administration/injection-site reactions in clinical trials that enrolled healthy adult volunteers. PMID- 22054119 TI - Pharmacogenetics of response to antipsychotics in patients with schizophrenia. AB - This review presents the findings of pharmacogenetic studies exploring the influence of gene variants on antipsychotic treatment response, in terms of both symptom improvement and adverse effects, in patients with schizophrenia. Despite numerous studies in the field, replicating findings across different cohorts that include subjects of different ethnic groups has been challenging. It is clear that non-genetic factors have an important contribution to antipsychotic treatment response. Differing clinical, demographic and environmental characteristics of the cohorts studied have added substantial complexity to the interpretation of the positive and negative findings of many studies. Pharmacogenomic genome-wide investigations are beginning to yield interesting data although they have failed to replicate the most robust findings of candidate gene studies, and are limited by the sample size, especially given the need for studying homogeneous cohorts. Most of the studies conducted on cohorts treated with single antipsychotics have investigated clozapine, olanzapine or risperidone response. These studies have provided some of the most replicated associations with treatment efficacy. Serotonergic system gene variants are significantly associated with the efficacy of clozapine and risperidone, but may have less influence on the efficacy of olanzapine. Dopamine D3 receptor polymorphisms have been more strongly associated with the efficacy of clozapine and olanzapine, and D2 genetic variants with the efficacy of risperidone. Serotonin influences the control of feeding behaviour and has been hypothesized to have a role in the development of antipsychotic-induced weight gain. Numerous studies have linked the serotonin receptor 2C (5-HT2C) -759-C/T polymorphism with weight gain. The leptin gene variant, -2548-G/A, has also been associated with weight gain in several studies. Pharmacogenetic studies support the role of cytochrome P450 enzymes and dopamine receptor variants in the development of antipsychotic induced movement disorders, with a contribution of serotonergic receptors and other gene variants implicated in the mechanism of action of antipsychotics. Clozapine-induced agranulocytosis has been associated with polymorphisms in the major histocompatibility complex gene (HLA). PMID- 22054122 TI - AIGO: towards a unified framework for the analysis and the inter-comparison of GO functional annotations. AB - BACKGROUND: In response to the rapid growth of available genome sequences, efforts have been made to develop automatic inference methods to functionally characterize them. Pipelines that infer functional annotation are now routinely used to produce new annotations at a genome scale and for a broad variety of species. These pipelines differ widely in their inference algorithms, confidence thresholds and data sources for reasoning. This heterogeneity makes a comparison of the relative merits of each approach extremely complex. The evaluation of the quality of the resultant annotations is also challenging given there is often no existing gold-standard against which to evaluate precision and recall. RESULTS: In this paper, we present a pragmatic approach to the study of functional annotations. An ensemble of 12 metrics, describing various aspects of functional annotations, is defined and implemented in a unified framework, which facilitates their systematic analysis and inter-comparison. The use of this framework is demonstrated on three illustrative examples: analysing the outputs of state-of the-art inference pipelines, comparing electronic versus manual annotation methods, and monitoring the evolution of publicly available functional annotations. The framework is part of the AIGO library (http://code.google.com/p/aigo) for the Analysis and the Inter-comparison of the products of Gene Ontology (GO) annotation pipelines. The AIGO library also provides functionalities to easily load, analyse, manipulate and compare functional annotations and also to plot and export the results of the analysis in various formats. CONCLUSIONS: This work is a step toward developing a unified framework for the systematic study of GO functional annotations. This framework has been designed so that new metrics on GO functional annotations can be added in a very straightforward way. PMID- 22054123 TI - Vibrationally induced dissociation of sulfuric acid (H2SO4). AB - One of the important reactive steps in Earth's atmosphere is the decomposition of H(2)SO(4) to H(2)O and SO(3). However, because the UV spectrum of H(2)SO(4) was not found up to 140 nm, alternative mechanisms, including vibrationally induced dissociation, were proposed. Using adiabatic reactive molecular dynamics (ARMD) simulations with validated force fields for the product and educt channels, it is shown through explicit atomistic simulation that by exciting the nu(9) (OH stretching-) mode, photodissociation can occur on the picosecond time scale. With the potential energy surfaces used in the present work, nu(9) = 4 is sufficient for this process. From a statistically significant number of trajectories (several thousands), vibrationally induced dissociation times are found to follow Gamma-distributions with most likely reaction times between 40 and 200 ps by depositing energies ranging from 40 to 60 kcal/mol, corresponding to 4 and 6 vibrational quanta in the OH stretching vibration. Because ARMD simulations allow multiple and long-time simulations, both nonstatistical, impulsive H-transfer and statistical, IVR-regimes of the decomposition reaction can be discussed in detail at an atomistic level. PMID- 22054124 TI - Boerhaave syndrome as a complication of colonoscopy preparation: a case report. AB - INTRODUCTION: Colonoscopy is one of the most frequently performed elective and invasive diagnostic interventions. For every colonoscopy, complete colon preparation is mandatory to provide the best possible endoluminal visibility; for example, the patient has to drink a great volume of a non-resorbable solution to flush out all feces. Despite the known possible nauseating side effects of colonoscopy preparation and despite the knowledge that excessive vomiting can cause rupture of the distal esophagus (Boerhaave syndrome), which is a rare but severe complication with high morbidity and mortality, it is not yet a standard procedure to provide a patient with an anti-emetic medication during a colon preparation process. This is the first report of Boerhaave syndrome induced by colonoscopy preparation, and this case strongly suggests that the prospect of being at risk of a severe complication connected with an elective colonoscopy justifies a non-invasive, inexpensive yet effective precaution such as an anti emetic co-medication during the colonoscopy preparation process. CASE PRESENTATION: A 73-year-old Caucasian woman was scheduled to undergo elective colonoscopy. For the colonoscopy preparation at home she received commercially available bags containing soluble polyethylene glycol powder. No anti-emetic medication was prescribed. After drinking the prepared solution she had to vomit excessively and experienced a sudden and intense pain in her back. An immediate computed tomography (CT) scan revealed a rupture of the distal esophagus (Boerhaave syndrome). After initial conservative treatment by endoluminal sponge vacuum therapy, she was taken to the operating theatre and the longitudinal esophageal rupture was closed by direct suture and gastric fundoplication (Nissen procedure). She recovered completely and was discharged three weeks after the initial event. CONCLUSIONS: To the best of our knowledge, this is the first report of a case of Boerhaave syndrome as a complication of excessive vomiting caused by colonoscopy preparation. The case suggests that patients who are prepared for a colonoscopy by drinking large volumes of fluid should routinely receive an anti-emetic medication during the preparation process, especially when they have a tendency to nausea and vomiting. PMID- 22054125 TI - Lack of association between apolipoprotein C3 gene polymorphisms and risk of coronary heart disease in a Han population in East China. AB - BACKGROUND: Several polymorphisms in the apolipoprotein C3 (APOC3) gene have been found association with hypertriglyceridemia(HTG), but the link with coronary heart disease(CHD) risk between ethnicities was still controversial. Among them, reseachers paid more attentions to the promoter polymorphisms T-455C and C-482T because both of them located in insulin-responsive element (IRE) and insulin was thought to exert its action by down-regulating APOC3 gene expression. The aim of this study was to investigate the association of the two polymorphisms of APOC3 with CHD in a Han population in East China. METHODS: TaqMan SNP Genotyping Assays were carried out to detect the genotypes of APOC3 gene, including the T-455C and C-482T, in 286 subjects with CHD and 325 controls without CHD. The levels of serum lipid profiles were also detected by biochemical methods. RESULTS: There was no difference of genotype frequencies and allele frequencies between the CHD population and the controls(P > 0.05). Compared with the most common genotype 455TT or -482CC, the variants had neither significantly increased CHD risk, nor the lipid variables showed any statistically relevant differences in the research population. The adjusted OR of CHD were 5.67 [0.27-18.74] and 0.75 [0.20-2.73] in carriers of the APOC3 -455C and -482T variants, respectively(P > 0.05). There was also no significant difference in APOC3 haplotype distribution in CHD and controls, but there was a strong linkage disequilibrium between T-455C and C-482T with D' = 0.9293, 0.8881, respectively(P < 0.0001). CONCLUSIONS: Our data did not support a relationship between the two polymorphisms of APOC3 gene and risk of CHD in the Han population in East China. PMID- 22054126 TI - Wetting transitions in two-, three-, and four-phase systems. AB - We discuss wetting of rough surfaces with two-phase (solid-liquid), three-phase (solid-water-air and solid-oil-water), and four-phase (solid-oil-water-air) interfaces mimicking fish scales. We extend the traditional Wenzel and Cassie Baxter models to these cases. We further present experimental observations of two , three-, and four-phase systems in the case of metal-matrix composite solid surfaces immersed in water and in contact with oil. Experimental observations show that wetting transitions can occur in underwater oleophobic systems. We also discuss wetting transitions as phase transitions using the phase-field approach and show that a phenomenological gradient coefficient is responsible for wetting transition, energy barriers, and wetting/dewetting asymmetry (hysteresis). PMID- 22054127 TI - The first call for the 'SNF-professor' stipends from the Swiss National Science Foundation. Editorial. PMID- 22054128 TI - Getting ready to translate: cytoplasmic maturation of eukaryotic ribosomes. AB - The ribosome is the 'universal ribozyme' that is responsible for the final step of decoding genetic information into proteins. While the function of the ribosome is being elucidated at the atomic level, in comparison, little is known regarding its assembly in vivo and intracellular transport. In contrast to prokaryotic ribosomes, the construction of eukaryotic ribosomes, which begins in the nucleolus, requires >200 evolutionary conserved non-ribosomal trans-acting factors, which transiently associate with pre-ribosomal subunits at distinct assembly stages and perform specific maturation steps. Notably, pre-ribosomal subunits are transported to the cytoplasm in a functionally inactive state where they undergo maturation prior to entering translation. In this review, I will summarize our current knowledge of the eukaryotic ribosome assembly pathway with emphasis on cytoplasmic maturation events that render pre-ribosomal subunits translation competent. PMID- 22054129 TI - Expanding the catalytic repertoire of DNAzymes by modified nucleosides. AB - Modified nucleoside triphosphates (dNTPs) are a versatile platform for the generation of high-density functionalized nucleic acids. The enzymatic polymerization of dNTPs allows the introduction of sensible functionalities that might not be compatible with the standard automated synthesis of oligonucleotides. Their application to in vitro selections, an elegant chemical approach to Darwinian evolution, delivers modified aptamers and catalytic nucleic acids with potentially enhanced properties. This review article highlights some recent synthetic examples of dNTPs bearing functionalities that are either found in the active site of protein enzymes or have been employed in organocatalysis and further underscores their usefulness in the development of some modified catalytic nucleic acids with special emphasis on M(2+)-independent RNA-cleaving DNAzymes. PMID- 22054130 TI - Water-stable fac-{TcO3}+ complexes - a new field of technetium chemistry. AB - The development of technetium chemistry has been lagging behind that of its heavier congener rhenium, primarily because the inherent radioactivity of all Tc isotopes has limited the number of laboratories that can study the chemistry of this fascinating element. Although technetium is an artificial element, it is not rare. Significant amounts of the isotope (99)Tc are produced every day as a fission byproduct in nuclear power plants. Therefore, a fundamental understanding of the chemistry of (99)Tc is essential to avoid its release into the environment. In this article the chemistry of technetium at its highest oxidation state (+VII) is reviewed with a special focus on recent developments which make water-stable complexes of the general type [TcO(3)(tacn-R)](+) (tacn-R = 1,4,7-triazacyclononane or derivatives) accessible. Complexes containing the fac-{TcO(3)}(+) core display a unique reactivity. In analogy to [OsO(4)] and [RuO(4)], complexes containing the fac-{TcO(3)}(+) core undergo with alkenes metal-mediated, vicinal cis-dihydroxylation reactions (alkene-glycol interconversion) in water via a (3+2)-cycloaddition reaction. Therefore, water stable fac-{(99m)TcO(3)}(+) complexes pave the way for a new labeling strategy for radiopharmaceutical applications, based on (3+2)-cycloaddition reactions. This new concept for the labeling of biomolecules with small [(99m)TcO(3)(tacn R)](+)-type complexes by way of a (3+2)-cycloaddition with alkenes is discussed in detail. The herein reported developments in high-valent technetium chemistry create a new field of research with this artificial element. This demonstrates the potential of fundamental research to provide new impetus of innovation for the development of new methods for radiopharmaceutical applications. PMID- 22054131 TI - Towards biologically active self-assemblies: model nucleotide chimeras. AB - With this article, we wish to give an overview of our main research activities assessing the potential of a suitable polymer modification of DNA fragments to self-assemble biologically active nanostructures. Specifically, the grafting of a hydrophobic polymer segment on DNA fragments results in amphiphilic nucleotide based macromolecules, which, owing to both chemical and physical incompatibility, organize in self-assembled structures either on surfaces or in aqueous solution. Through the combination of the existing know-how in polymer chemistry with modern analytical techniques, we are currently focusing on establishing the mechanism of self-assembly of the polymer-modified nucleotide sequences in solution and on surfaces prior to the assessment of their hybridization capacity once involved in the ensemble. With the evaluation of the potential of the functional nanostructures to undergo biological-like adhesion through hybridization one can eventually foresee that the optimal functionality of these bio-inspired systems could be fine-tuned for biological applications such as drug delivery, gene therapy, tissue engineering and the design of either biomedical devices or biosensors. PMID- 22054132 TI - Geochemical compositions of marine fossils as proxies for reconstructing ancient environmental conditions. AB - A brief summary is given here about some of the geochemical methodologies that are often used to obtain information from fossils and sediments about the past environment. Such methods are frequently applied in our project in which the formation of Paleogene phosphate sequences in North Africa is investigated. These layers were deposited in shallow marine seas during a period of extreme warm climate with a high CO(2) concentration in the atmosphere. Some of the characteristics of this greenhouse interval are similar to the modern anthropogenic situation hence it is intensively investigated from several aspects by many scientists. Here the geochemical compositions of fossils deposited during this time are discussed, focusing on how the data are obtained and how they could be evaluated in terms of palaeo-environmental conditions. PMID- 22054133 TI - Field-controlled self-assembly and disassembly of colloidal nanoparticles. AB - Self-assembly of nanoparticles is one of the most promising methods for the preparation of novel materials and devices with exceptional properties. In order to control nanoparticles self-assembly, an understanding of their interactions is absolutely necessary. One convenient way to achieve a control on their interaction is through the use of external fields. Here we provide two different examples of how interparticle interactions are affected by interactions with external fields. In the first case, magnetic fields are used to induce dipolar interactions among concentrated suspension of superparamagnetic nanocolloids, which cause them to self-assemble into dense chain-like anisotropic structures, used as templates for the growth of porous materials with tunable properties. In the second case, it is shown how more commonly employed but less understood flow fields interact with clusters of particles, and lead to their restructuring or disassembly depending upon the shear stress applied. PMID- 22054134 TI - Towards macromolecular architectures of corannulene. AB - In an attempt to introduce corannulene chemistry to macromolecular science, my research program is dedicated to synthetic strategies leading to corannulene based polymers with interesting architectures and properties. In this brief account, I will discuss the synthesis of a variety of corannulene-based building blocks (monomers) and their utility in the preparation of a wide range of corannulene-rich macromolecular structures. PMID- 22054135 TI - New catalytic asymmetric strategies to access chiral aldehydes. AB - The present article describes the recent catalytic asymmetric methods developed in our group to access enantioenriched chiral aldehydes. We are generally aiming at developing complementary strategies based on either homogeneous organometallic catalysts or amino-catalysts and sometimes on a combination of both. Recent successes comprise a perfectly redox-economical iridium-catalyzed asymmetric isomerization of primary allylic alcohols under very mild conditions and the development of a transition metal-catalyzed anti-Markovnikov asymmetric hydroboration of 1,1-disubstituted olefins. The developments of these two processes along with preliminary mechanistic investigations are presented herein. PMID- 22054136 TI - New carbon- and sulfur-based ligands in catalysis. AB - Homogeneous catalysis is a field of research that has gained central importance in both organic and inorganic chemistry and the use of well-defined ligand systems in the synthesis of transition metal complexes has had an enormous impact on the development of such catalysts. Neutral, two-electron donor ligands based on phosphorous and nitrogen have been tremendously successful as ancillary entities for late-transition metal (LTM) catalysts, whereas ligands based on anionic nitrogen, oxygen and the cyclopentadienyl motif (Cp(-)) have propelled early-transition metal (ETM) catalysis forward. We believe that expanding the ligand families capable of acting as successful entities in metal-mediated reactivity and catalysis is crucial for future discoveries in this field. Research in our group therefore tries to identify new non-chiral and chiral ligands for late-transition metal chemistry that are based on neutral, two electron carbon and sulfur donor atoms. In particular, we have until now focused on the development of modular, monodentate N-heterocyclic carbene ligands (NHCs) that can serve as a basis for the development of chiral ligand frameworks for the application to asymmetric catalytic transformations. In the second major research project developed over the last six years, we have started an investigation on the use of chelating sulfoxide-based ligands in asymmetric late transition-metal based catalysis. PMID- 22054139 TI - Coupling of a microfluidic mixer to a Fourier-transform infrared spectrometer for protein-conformation studies. AB - The biological properties of a protein critically depend on its conformation, which can vary as a result of changes in conditions such as pH or following the addition of various substances. Being able to reliably assess the quality of protein structures under various conditions is therefore of crucial importance. Infrared (IR) spectroscopy of the Amide I band of proteins is a powerful method for the determination of protein conformations and further allows the analysis of continuously flowing solutions of the target molecule. Here, a commercial Fourier transform infrared spectrometer was coupled to a microfluidic mixer to allow the on-line monitoring of protein conformation under varying conditions. The validity of the concept was demonstrated by continuously recording the variations of the IR spectrum of poly-L-lysine resulting from repetitive, pH-induced conformational changes. PMID- 22054140 TI - [Maurice Cosandey, an ambassador of chemistry]. PMID- 22054142 TI - Psoriasis. AB - Psoriasis is a common relapsing and remitting immune-mediated inflammatory disease that affects the skin and joints. This review focuses on current immunogenetic concepts, key cellular players, and axes of cytokines that are thought to contribute to disease pathogenesis. We highlight potential therapeutic targets and give an overview of the currently used immune-targeted therapies. PMID- 22054143 TI - Tuberculosis pathogenesis and immunity. AB - Despite the development of potentially curative chemotherapy, tuberculosis (TB) continues to cause increasing worldwide morbidity and is a leading cause of human mortality in the developing world. Recent advances in bacterial molecular genetics, immunology, and human genetics have yielded insight into the molecular determinants of virulence, the immune responses that are essential for restricting progressive disease, and the determinants of immunopathology in TB. Despite these advances, a large knowledge gap still exists that limits the development and testing of new interventions, including novel drugs and efficacious vaccines. This review focuses on our current knowledge of TB pathogenesis and immunity that has been derived from in vitro and in vivo studies. In addition, it highlights topics that need to be better understood to provide improved means of controlling TB worldwide. PMID- 22054144 TI - Tipping the balance: the pathophysiology of obesity and type 2 diabetes mellitus. AB - Obesity plays a major role in the development of type 2 diabetes mellitus, and it has long been accepted that weight loss plays a significant role in diabetes therapy. This weight loss has traditionally been accomplished through lifestyle changes including diet and exercise. What has only more recently gained acceptance is that bariatric surgery may have a role to play in diabetes therapy as well. This article discusses the pathophysiology of type 2 diabetes mellitus and obesity and provides a basic understanding of these diseases, which forms the basis for understanding the importance of weight loss in their treatment. PMID- 22054146 TI - Epidemiology and economic impact of obesity and type 2 diabetes. AB - Obesity has become a major public health concern in the United States and the rest of the world. This disease carries significant health risks that encompass several organ systems. Type 2 diabetes mellitus is a major comorbidity of obesity that predisposes patients to significant end-organ damage. The prevalence of obesity and diabetes is increasing worldwide, and the economic impact of these diseases currently assumes a significant portion of health care expenditure. These factors mandate implementation of therapeutic medical and surgical strategies that target prevention and treatment of obesity and its related medical conditions. PMID- 22054145 TI - Physiology of weight loss surgery. AB - The clinical outcomes achieved by bariatric surgery have been impressive. However, the physiologic mechanisms and complex metabolic effects of bariatric surgery are only now beginning to be understood. Ongoing research has contributed a large amount of data and shed new light on the science behind obesity and its treatment, and this article reviews the current understanding of metabolic and bariatric surgery physiology. PMID- 22054147 TI - The economic costs of obesity and the impact of bariatric surgery. AB - The obesity epidemic has far-reaching implications for the economic and health care future in the United States. Treatments that show reduction in health care costs over time should be approved and made available to as many patients as possible. It is our opinion that bariatric surgery meets this criterion. However, bariatric surgery cannot provide the impact necessary for reduction in health care and economic costs on a national scale. The obesity epidemic must be addressed by policy efforts at the local, state, and national levels. As experts on obesity, bariatric surgeons must be prepared to guide and inform these efforts. PMID- 22054148 TI - The history and evolution of bariatric surgical procedures. AB - The search for the ideal weight loss operation began more than 50 years ago. Surgical pioneers developed innovative procedures that initially created malabsorption, then restricted volume intake, and eventually combined both techniques. Variations, alterations, and modifications of these original procedures, combined with intense efforts to follow and document outcomes, have led to the evolution of modern bariatric surgery. More recent research has focused on the hormonal and metabolic effects of these procedures. These discoveries at the cellular level will help develop possible mechanisms of weight loss and comorbidity reduction beyond the traditional explanation of reduced food consumption and malabsorption. PMID- 22054149 TI - Surgical treatment for morbid obesity: the laparoscopic Roux-en-Y gastric bypass. AB - Over the past 20 years bariatric surgery proved to be a valid treatment for reduction and elimination of obesity-related diseases and long-term sustainable weight loss. Minimally invasive or laparoscopic techniques such as laparoscopic Roux-en-Y (LRNY) have replaced open procedures. Many factors play important roles in the small intricacies and variations of the procedure, chief of which is the creation and size of the gastrojejunostomy. Regardless of the variations in technique, the LRNY remains the gold standard for the surgical treatment of clinically severe or morbid obesity, with relatively low morbidity and mortality. PMID- 22054150 TI - Complications of laparoscopic Roux-en-Y gastric bypass. AB - Despite the well-documented safety of laparoscopic RYGB, several short-term and long-term complications, with varying degrees of morbidity and mortality risk, are known to occur. Bariatric surgeons, all too familiar with these complications, should be knowledgeable in risk-reduction strategies to minimize the incidence of complication occurrence and recurrence. Bariatric and nonbariatric surgeons who evaluate and treat abdominal pain should be familiar with these complications to facilitate early recognition and intervention, thereby minimizing the associated morbidity and mortality. PMID- 22054151 TI - Evolution of laparoscopic adjustable gastric banding. AB - This article reviews the use of laparoscopic adjustable gastric banding in the United States today. It comments on the history of the procedure as well as technical aspects of the operation. Short-term and long-term outcomes of the procedure are examined, and the advantages and disadvantages of this procedure in comparison with the laparoscopic gastric bypass are discussed. PMID- 22054152 TI - Complications of adjustable gastric banding. AB - Adjustable gastric banding (AGB) has become increasingly used by bariatric surgeons and their patients as the surgical weight loss procedure of choice. The popularity of this procedure is in large part a result of the remarkable safety profile and low initial complication rate. Complications of AGB were initially believed to be minor and infrequent, but longer-term studies have increasingly described complications that lead to revisional surgery. In addition, a larger fraction of patients fail to lose weight than with other surgical weight loss procedures, frequently necessitating conversion to these other options. PMID- 22054153 TI - Sleeve gastrectomy. AB - Sleeve gastrectomy (SG) was originally performed as the restrictive component of the duodenal switch procedure. This partial vertical gastrectomy served to reduce gastric capacity and initiate short-term weight loss while the malabsorptive component of the operation (biliopancreatic diversion) provided the long-term weight loss. Some patients, however, could not undergo the intestinal bypass, and early investigations found that substantial weight loss occurred with the SG alone. The sleeve then developed into a risk management strategy for very large or high-risk patients who would not tolerate a longer or higher-risk procedure. PMID- 22054154 TI - Biliopancreatic diversion with duodenal switch. AB - The biliopancreatic diversion with a duodenal switch (BPD-DS) is a less commonly performed but very effective bariatric procedure that has been in existence for more than 20 years. It is particularly effective for the resolution of diabetes and is associated with the highest weight loss among other bariatric operations. Typically, the BPD-DS is not associated with postgastrectomy symptoms, such as dumping and marginal ulceration. Because of its complexity, it has usually been performed by laparotomy in the past; but, more recently, minimally invasive techniques are being used with acceptable risk. PMID- 22054155 TI - Impact of bariatric surgery on comorbidities. AB - Published data show that bariatric surgery not only leads to significant and sustained weight loss but also resolves or improves multiple comorbidities associated with morbid obesity. Evidence suggests that the earlier the intervention the better the resolution of comorbidities. Patients with metabolic syndrome and comorbidities associated with morbid obesity should be promptly referred for consideration for bariatric surgery earlier in the disease process. PMID- 22054156 TI - Bariatric surgery outcomes. AB - Obesity is associated with an increased risk of death, and morbid obesity carries a significant risk of life-threatening complications such as heart disease, diabetes, and high blood pressure. Bariatric surgery is recognized as the only effective treatment of morbid obesity. The estimated number of bariatric operations performed in the United States in 2008 was more than 13 times the number performed in 1992. Despite this increase, only 1% of the eligible morbidly obese population are currently treated with bariatric surgery. PMID- 22054157 TI - Adolescent bariatric surgery. AB - Obesity has become an increasingly serious problem in pediatric and adolescent populations in the United States. Although bariatric surgery has been offered to morbidly obese adolescents for the past several decades, it remains controversial. However, the benefits of weight loss surgery in this population have been realized, particularly its long-term physical and emotional effects on adolescents. This article reviews the demographics and health implications of adolescent obesity, describes the most common adolescent bariatric surgical procedures and their outcomes, discusses the ethical issues involved in elective surgery in this population, and outlines the key components of an adolescent bariatric surgical program. PMID- 22054158 TI - Revisional bariatric surgery. AB - With the increase in bariatric surgical procedures, an increase in revision operations is expected. A thorough preoperative work-up is essential to formulate an appropriate revision strategy. Outcomes vary according to the primary operation and chosen approach to revision. Recent studies have shown acceptably low complication rates and good weight loss with the associated health benefits. Although there is no direct evidence in the form of randomized studies indicating which patients with inadequate weight loss or weight regain will benefit most from revision, or to support one particular revision approach rather than another, it is possible to develop general, effective strategies. PMID- 22054159 TI - Future directions in bariatric surgery. AB - Bariatric surgery is a field in rapid evolution, and the speed of this evolution has been accelerating over the last several decades. A thorough understanding of past developments is crucial to anticipating the future intelligently. The trends that have driven evolution historically often persist, and continue to be influential in the future. With this in mind, this article briefly outlines the historical and current trends in bariatric surgery, and follows the trajectory of these trends into the future to anticipate the technologies and techniques that will be most important to the field in the coming years. PMID- 22054160 TI - Bariatric and metabolic surgery. PMID- 22054161 TI - Bariatric and metabolic surgery. PMID- 22054162 TI - Child-to-parent donation--consideration of age and ethnicity. PMID- 22054163 TI - Area of Wharton's jelly as an estimate of the thickness of the umbilical cord and its relationship with estimated fetal weight. AB - BACKGROUND: To build a reference curve for the area of Wharton's jelly (WJ) in low-risk pregnancies from 13 to 40 weeks and to assess its relationship with estimated fetal weight (EFW). METHODS: 2,189 low-risk pregnancies had the area of WJ estimated by ultrasound and the 10th, 50th and 90th percentiles calculated using a third-degree polynomial regression procedure. EFW by ultrasound was correlated with the measurement of the area of WJ. RESULTS: The area of WJ increased according to gestational age (R2 = 0.64), stabilizing from the 32nd week onwards. There was a significant linear correlation between area of WJ and EFW up to 26 weeks (R = 0.782) and after that 5t remained practically constant (R = 0.047). CONCLUSION: The area of WJ increases according to gestational age, with a trend to stabilize at around 32 weeks of gestation. It is also linearly correlated with EFW only up to 26 weeks of gestation. PMID- 22054164 TI - Optimizing suture middle cerebral artery occlusion model in C57BL/6 mice circumvents posterior communicating artery dysplasia. AB - The suture middle cerebral artery occlusion (MCAO) model is used worldwide in both academia and industry. However, the variable occurrence of dysplasia in posterior communicating arteries (PcomAs) induces high mortality and instability in permanent MCAO models, limiting the model's application to transient focal ischemia. In particular, high mortality in intraluminal suture MCAO models is associated with the dysplasia of PcomAs in C57BL/6 mice. Optimization of silicone coating length is critical for reducing mortality and generating stable infarct in this model. The aim of our study is to reduce mortality and improve the reproducibility of the intraluminal suture MCAO model in C57BL/6 mice, which have high variation in PcomA dysplasia. Adult male C57BL/6 mice (n=38) underwent MCAO using sutures with various diameters and silicone coating lengths. The occlusion of cerebral vessels was examined by synchrotron radiation live angiography. The morphology of PcomAs was examined under a microscope after MICROFIL((r)) infusion. Neurological outcome, infarct volume, and mortality were examined within 28 days. Optimizing the silicone coating on an 8-0 suture tip, we were able to reduce the model mortality to zero after permanent occlusion in C57BL/6 and produce stable brain infarct volume independent of the patency of PcomAs. PMID- 22054165 TI - Validation and comparison of models to predict non-sentinel lymph node metastasis in breast cancer patients. AB - Several models for predicting the risk of non-sentinel lymph node (NSLN) metastasis in breast cancer patients with positive sentinel lymph nodes (SLNs) have been developed. The purpose of this study was to validate and compare these models in Chinese patients. A total of 159 breast cancer patients with positive SLNs treated at our institution were included. Among them, 81 (50.9%) patients had at least one NSLN involvement. The Cambridge, Mou, Mayo, Tenon, MDA, Memorial Sloan-Kettering Cancer Center (MSKCC), Ljubljana, SNUH, Turkish, Louisville, Stanford, and Saidi models were evaluated and compared using receiver operating characteristic (ROC) curves, calibration plots, and false negative (FN) rates. The Cambridge and Mou models outperformed the others, both with area under the ROC curves (AUCs) of 0.73. The Mayo, Tenon, MDA, MSKCC, Turkish, Ljubljana, SNUH, and Louisville models had AUCs of 0.68, 0.66, 0.66, 0.64, 0.63, 0.62, 0.61, and 0.60, respectively. The Stanford and Saidi models did not present any discriminative capabilities, with AUCs of 0.54 and 0.50, respectively. The Cambridge, MSKCC, and Mayo models were well calibrated. With adjusted thresholds, the Mayo model outperformed the others by classifying the highest proportion of patients (20%) into the low-risk group. Our study revealed that the Cambridge and Mou models performed well in Chinese patients. The ROC curves, calibration plots, and FN rates should be used together for the accurate evaluation of prediction models. Selection of these models should be based on the clinicopathological features of the targeted population. The models specifically designed for patients with micrometastases or macrometastases of SLNs are needed in the future. PMID- 22054166 TI - Application of the Seattle Heart Failure Model in patients on cardiac resynchronization therapy. AB - BACKGROUND: The Seattle Heart Failure Model (SHFM) is a multimarker risk assessment tool able to predict outcome in heart failure (HF) patients. AIM: To assess whether the SHFM can be used to risk-stratify HF patients who underwent cardiac resynchronization therapy with (CRT-D) or without (CRT) an implantable defibrillator. METHODS AND RESULTS: The SHFM was applied to 342 New York Heart Association class III-IV patients who received a CRT (23%) or CRT-D (77%) device. Discrimination and calibration of SHFM were evaluated through c-statistics and Hosmer-Lemeshow (H-L) goodness-of-fit test. Primary endpoint was a composite of death from any cause/cardiac transplantation. During a median follow-up of 24 months (25th-75th percentile [pct]: 12-37 months), 78 of 342 (22.8%) patients died; seven patients underwent urgent transplantation. Median SHFM score for patients with endpoint was 5.8 years (25th-75th pct: 4.25-8.7 years) versus 8.9 years (25th-75th pct: 6.6-11.8 years) for those without (P < 0.001). Discrimination of SHFM was adequate for the endpoint (c-statistic always ranged around 0.7). The SHFM was a good fit of death from any cause/cardiac transplantation, without significant differences between observed and SHFM predicted survival. CONCLUSION: The SHFM successfully stratifies HF patients on CRT/CRT-D and can be reliably applied to help clinicians in predicting survival in this clinical setting. PMID- 22054168 TI - Comparison of the Bayley II Mental Developmental Index and the Bayley III Cognitive Scale: are we measuring the same thing? AB - AIM: To better understand differences between Bayley Scales 3rd edition (Bayley III) Cognitive Scale and Bayley Scales 2nd edition (Bayley II) Mental Developmental Index (MDI) in 18-22-month-old children born term and preterm and to create a conversion algorithm using Bayley II MDI to calculate Bayley III Cognitive score. METHODS: This study included 51 term and 26 preterm children between 18 and 22 months, ages adjusted for prematurity. Children's scores on Bayley II MDI and Bayley III Cognitive Scale were compared using t-tests. The items from Bayley II MDI were used to calculate a score for the Bayley III Cognitive Scale. ANCOVA was used to create a conversion scale. RESULTS: Bayley III Cognitive scores were significantly higher than Bayley II MDI scores for term and preterm toddlers combined and separately (p < .0001). A conversion formula to convert Bayley II MDI to a Bayley III Cognitive score was calculated. CONCLUSION: Term and preterm children had similarly elevated scores on the Bayley III calculated Cognitive score compared to the previous Bayley II MDI score. The use of a conversion algorithm may be helpful in studies that used both Bayley editions to get comparable outcome measurements within a clinical or research paradigm. PMID- 22054169 TI - Mycobacterium genavense as a cause of subacute pneumonia in patients with severe cellular immunodeficiency. AB - BACKGROUND: Mycobacterium genavense is a rare nontuberculous mycobacteria (NTM). Human infections are mostly disseminated in the setting of the AIDS epidemic or the use of aggressive immunosuppressive treatments. M. genavense culture is fastidious, requiring supplemented media. Pulmonary involvement rarely occurs as a primary localization. CASES PRESENTATION: We report here two patients with pneumonia as the predominant manifestation of M. genavense infection: one kidney transplanted patient and one HIV-infected patient. Both patients were initially treated with anti-tuberculous drugs before the identification of M. genavense on sputum or broncho-alveolar lavage fluid culture. A four-drug regimen including clarithromycin and rifabutin was started. Gamma interferon has been helpful in addition to antimycobacterial treatment for one patient. CONCLUSION: Clinicians should be aware that M. genavense could be the etiologic agent of sub-acute pneumonia mimicking tuberculosis in patients with cellular immunodeficiency status. PMID- 22054170 TI - Skeletal isomerization of butene in ferrierite: assessing the energetic and structural differences between carbenium and alkoxide based pathways. AB - In this study, the results from a systematic analysis of two different mechanisms for the skeletal isomerization of cis-butene to isobutene in ferrierite (FER) are presented. One involves a conventional mechanism that proceeds via stable alkoxide intermediates and the other is one which proceeds via carbenium ions only. A 27T QM cluster model has been used in this study, which is described using the M06-2X DFT functional. It is found that the alkoxide intermediates formed over the course of the conventional pathway are considerably lower in energy than the carbenium ion formed over the course of the alternate pathway. However, the rate determining step in the latter pathway is predicted to be almost 10 kcal/mol lower in energy. The higher barrier for the latter process is due to the inherent stability of the alkoxide intermediates formed within FER. These results appear to suggest that while these intermediates are formed over the course of the reaction, the skeletal isomerization of linear butenes to form isobutene in FER may occur via a carbenium based mechanism. This proposal is consistent with experimental results that show alkoxide intermediates are experimentally observed species. PMID- 22054171 TI - Laparoscopic myomectomy of a subserous pedunculated fibroid at 14 weeks of pregnancy: a case report. AB - INTRODUCTION: Uterine leiomyomas are seen in 1.6% to 4% of pregnancies. With the increasing age of obstetric patients, more cases are being encountered during pregnancy. CASE PRESENTATION: We report the case of a 31-year-old Caucasian woman with acute recurrent abdominal pain due to a subserous fundic myoma, measuring 48 * 52 * 63 mm, with an implantation base of 22 * 18 mm, which was successfully treated by laparoscopy at 14 weeks of pregnancy. At a gestational age of week 40, the patient spontaneously delivered a healthy 3216 g girl baby. CONCLUSION: As far as we know, this is the first reported case of laparoscopic myomectomy this early during a pregnancy. Our experience together with an analysis of cases reported in the literature suggests that myomectomy during pregnancy may be considered safe, but only in the hands of experienced laparoscopic surgeons. There are a few reports in the literature about laparoscopic myomectomy during the first half of pregnancy that demonstrate its feasibility in selected cases. Some technical tools could improve the procedure with a minimum of risk for the ongoing pregnancy. PMID- 22054172 TI - Conjugated polymer nanoparticles for light-activated anticancer and antibacterial activity with imaging capability. AB - A new water-soluble conjugated polymer containing fluorene and boron dipyrromethene repeat units in the backbones (PBF) that exhibits red emission was synthesized and characterized. Cationic PBF forms uniform nanoparticles with negatively charged disodium salt 3,3'-dithiodipropionic acid (SDPA) in aqueous solution through electrostatic interactions. The nanoparticles display absorption maximum at 550 nm and emission maximum at 590 nm. Upon photoexcitation with white light (400-800 nm) with 90 and 45 mW.cm(-2) for bacteria and cancer cells killing respectively, PBF nanoparticles can sensitize the oxygen molecule to readily produce reactive oxygen species (ROS) for rapidly killing neighboring bacteria and cancer cells. Furthermore, PBF nanoparticles concurrently provide optical imaging capability. PBF nanoparticles are therefore a promising multifunctional material for treating cancers and bacteria infections, while concurrently providing optical monitoring capabilities. PMID- 22054173 TI - Simulation of total dietary iodine intake in Flemish preschool children. AB - The aim of the present study was to calculate the distribution of total iodine intake among Flemish preschoolers and to identify the major sources contributing to iodine intake. A simulation model using a combination of deterministic and probabilistic techniques was utilised. Scenario analyses were performed to assess iodine intake via dairy products, industrially added iodised salt in bread and discretionarily added iodised household salt. Relevant data from 3-d estimated dietary records of 696 preschoolers 2.5-6.5 years old were used. Usual iodine intakes were calculated using the Iowa State University method. With a more generalised utilisation of iodised salt in bread (44 % of the bakers in 2011 instead of 12 % in 2002), mean iodine intake increased from 159 to 164 MUg/d using the McCance and Widdowson's food composition table and from 104 to 109 MUg/d using the German food composition table. The percentage of preschoolers with an iodine intake below the estimated average requirement (65 MUg/d) decreased from 5-12 to 4-9 %, while the percentage of preschoolers with an iodine intake above the tolerable upper intake level (300 MUg/d) remained constant (0.3 4 %). Mean iodine intake via food supplements was 4.2 MUg/d (total population) and 16.9 MUg/d (consumers only). Both in 2002 and 2011, sugared dairy products, milk and iodised salt (21.4, 13.1, and 8.7 %, respectively in 2011) were the main contributors to total iodine intake. In conclusion, dietary iodine intake could still be improved in Flemish preschoolers. The use of adequately iodised household salt and the more generalised use of iodised salt by bakers should be further encouraged. PMID- 22054174 TI - Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity. AB - BACKGROUND: The collagen antibody-induced arthritis (CAIA) model, which employs a cocktail of monoclonal antibodies (mAbs) to type II collagen (CII), has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not all mAbs to CII are capable of inducing arthritis because one of the initial events is the formation of collagen-antibody immune complexes on the cartilage surface or in the synovium, and subsequent activation of the complement by the complexes induces arthritis, suggesting that a combination of mAbs showing strong ability to bind mouse CII and activate the complement may effectively induce arthritis in mice. In the present study, we examined the relationship between the induction of arthritis by the combination of IgG2a (CII-6 and C2A-12), IgG2b (CII 3, C2B-14 and C2B-16) and IgM (CM-5) subclones of monoclonal antibodies (mAb) of anti-bovine or chicken CII and the ability of mAbs to activate complement and bind mouse CII. METHODS: DBA/1J mice were injected with several combinations of mAbs followed by lipopolysaccharide. Furthermore, the ability of mAbs to activate the complement and bind mouse CII was examined by ELISA. RESULTS: First, DBA/1J mice were injected with the combined 4 mAbs (CII-3, CII-6, C2B-14, and CM-5) followed by lipopolysaccharide, resulting in moderate arthritis. Excluding one of the mAbs, i.e., using only CII-3, CII-6, and C2B-14, induced greater inflammation of the joints. Next, adding C2A-12 but not C2B-16 to these 3 mAbs produced more severe arthritis. A combination of five clones, consisting of all 5 mAbs, was less effective. Histologically, mice given the newly developed 4-clone cocktail had marked proliferation of synovial tissues, massive infiltration by inflammatory cells, and severe destruction of cartilage and bone. Furthermore, 4 of the 6 clones (CII-3, CII-6, C2B-14, and C2A-12) showed not only a strong cross reaction with mouse CII but also marked activation of the complement in vitro. CONCLUSION: The combination of 4 mAbs showing strong abilities to activate the complement and bind mouse CII effectively induced arthritis in DBA/1J mice. This in vitro system may be useful for the selection of mAbs associated with the development of arthritis. PMID- 22054175 TI - The role of neuropsychological performance in the relationship between chronic pain and functional physical impairment. AB - OBJECTIVE: In this study, the relationship between pain intensity, neuropsychological, and physical function in adult chronic pain patients was examined. DESIGN: Thirty participants with chronic pain completed neuropsychological tests tapping mental processing speed, memory, and executive function. Pain intensity was measured with three visual analog scales and the Pain Rating Index of the McGill Pain Questionnaire. A grip strength test, the 6 minute walk test, the Unipedal Stance Test and the Lifting Low Test were administered in order to obtain a performance-based measure of physical capacity. Self-reported physical ability was assessed with the Disability Rating Index and the Short Form-36 Physical Functioning, and Role Physical scales. Psychosocial function was examined using the Mental Health and Role Emotional subscales of the Short Form-36. SETTING: The study was set in two outpatient physical therapy clinics in The Netherlands. RESULTS: The analysis showed that a lower mental processing speed was related to a higher level of pain, as well as to a lower performance-based and self-reported physical functioning. In addition, both performance-based and self-reported physical function revealed an inverse correlation with pain intensity. Psychosocial function turned out to be an important mediator of the relationship between pain and self-reported, but not performance-based, physical function. Mental processing speed, on the other hand, was found to mediate the relationship between pain and performance-based physical functioning. CONCLUSION: The results suggest that in chronic pain patients, mental processing speed mediates the relationship between pain and physical function. PMID- 22054176 TI - Myosin II activity dependent and independent vinculin recruitment to the sites of E-cadherin-mediated cell-cell adhesion. AB - BACKGROUND: Maintaining proper adhesion between neighboring cells depends on the ability of cells to mechanically respond to tension at cell-cell junctions through the actin cytoskeleton. Thus, identifying the molecules involved in responding to cell tension would provide insight into the maintenance, regulation, and breakdown of cell-cell junctions during various biological processes. Vinculin, an actin-binding protein that associates with the cadherin complex, is recruited to cell-cell contacts under increased tension in a myosin II-dependent manner. However, the precise role of vinculin at force-bearing cell cell junctions and how myosin II activity alters the recruitment of vinculin at quiescent cell-cell contacts have not been demonstrated. RESULTS: We generated vinculin knockdown cells using shRNA specific to vinculin and MDCK epithelial cells. These vinculin-deficient MDCK cells form smaller cell clusters in a suspension than wild-type cells. In wound healing assays, GFP-vinculin accumulated at cell-cell junctions along the wound edge while vinculin-deficient cells displayed a slower wound closure rate compared to vinculin-expressing cells. In the presence of blebbistatin (myosin II inhibitor), vinculin localization at quiescent cell-cell contacts was unaffected while in the presence of jasplakinolide (F-actin stabilizer), vinculin recruitment increased in mature MDCK cell monolayers. CONCLUSION: These results demonstrate that vinculin plays an active role at adherens junctions under increased tension at cell-cell contacts where vinculin recruitment occurs in a myosin II activity-dependent manner, whereas vinculin recruitment to the quiescent cell-cell junctions depends on F-actin stabilization. PMID- 22054177 TI - Bayesian estimation of mycophenolate mofetil in lung transplantation, using a population pharmacokinetic model developed in kidney and lung transplant recipients. AB - BACKGROUND AND OBJECTIVES: The immunosuppressive drug mycophenolate mofetil is used to prevent rejection after organ transplantation. In kidney transplant recipients, it has been demonstrated that adjustment of the mycophenolate mofetil dose on the basis of the area under the concentration-time curve (AUC) of mycophenolic acid (MPA), the active moiety of mycophenolate mofetil, improves the clinical outcome. Because of the high risks of rejections and infections in lung transplant recipients, therapeutic drug monitoring of the MPA AUC might be even more useful in these patients. The aims of this study were to characterize the pharmacokinetics of MPA in lung and kidney transplant recipients, describe the differences between the two populations and develop a Bayesian estimator of the MPA AUC in lung transplant recipients. METHODS: In total, 460 MPA concentration time profiles from 41 lung transplant recipients and 116 kidney transplant recipients were included. Nonlinear mixed-effects modelling was used to develop a population pharmacokinetic model. Patients were divided into an index dataset and a validation dataset. The pharmacokinetic model derived from the index dataset was used to develop a Bayesian estimator, which was validated using the 35 lung transplant recipients' profiles from the validation dataset. RESULTS: MPA pharmacokinetics were described using a two-compartment model with lag time, first-order absorption and first-order elimination. The influence of ciclosporin co-treatment and the changes over time post-transplantation were included in the model. Lung transplant recipients had, on average, a 53% slower absorption rate and 50% faster MPA apparent oral clearance than kidney transplant recipients (p < 0.001). In lung transplant recipients, the bioavailability was, on average, 31% lower in patients with cystic fibrosis than in patients without cystic fibrosis (p < 0.001). The Bayesian estimator developed using the population pharmacokinetic model--and taking into account ciclosporin co-treatment, cystic fibrosis and time post-transplantation, with concentrations measured at 0, 1 and 4 hours after mycophenolate mofetil dose administration--resulted in a non significant bias and mean imprecision of 5.8 mg . h/L. This higher imprecision compared with those of similar estimators that have previously been developed in kidney transplantation might have been caused by the high MPA pharmacokinetic variability seen in the lung transplant recipients and by the fact that a large proportion of the patients did not receive ciclosporin, which reduces variability in the elimination phase of MPA by blocking its enterohepatic cycling. CONCLUSION: Lung transplant recipients have a slower MPA absorption rate and faster apparent oral clearance than kidney transplant recipients, while cystic fibrosis results in lower MPA bioavailability. A Bayesian estimator using MPA concentration-time samples at 0, 1 and 4 hours post-dose had the best predictive performance. PMID- 22054178 TI - Characterization of Staphylococcus aureus isolates from white-brined Urfa cheese. AB - The aim of this study was to investigate the presence of Staphylococcus aureus and staphylococcal enterotoxin (SE) genes in Urfa cheese samples and to characterize the enterotoxigenic potential of these isolates. From a total of 127 Urfa cheese samples, 53 isolates (from 41.7% of the samples) were identified by a species-specific PCR assay as S. aureus. Of these isolates, 40 (75.5%) gave positive PCR results for the 3' end of the coa gene. The coa-positive S. aureus strains were characterized for their population levels and enterotoxigenic properties, including slime factor, beta-lactamase, antibiotic susceptibilities, production of the classical SEs (SEA through SEE), in both cheese and liquid cultures by enzyme-linked immunosorbent assay (ELISA) and for the presence of specific genes, including classical SE genes (sea through see), mecA, femA, and spa, by PCR. The genetic relatedness among the coa-positive S. aureus isolates was investigated by PCR-based restriction fragment length polymorphism (RFLP) analysis and the 23S rRNA gene spacer. The 23S rRNA gene spacer and coa RFLP analysis using AluI and Hin6I revealed 14 different patterns. SEB, SEC, and SEA and SEE were detected by ELISA in three cheese samples. Fourteen S. aureus strains harbored enterotoxin genes sea through see, and three strains carried multiple toxin genes. The most commonly detected toxin gene was sec (25% of tested strains). Of the 40 analyzed S. aureus strains, 3 (7.5%) were mecA positive. Based on tandem repeats, four coa and spa types were identified. The results of this study indicate that S. aureus and SEs are present at significant levels in Urfa cheese. These toxins can cause staphylococcal food poisoning, creating a serious hazard for public health. PMID- 22054179 TI - Growth of group II Clostridium botulinum strains at extreme temperatures. AB - The minimum and maximum growth temperatures and the maximum growth rates at 10, 30, 37, and 40 degrees C were determined for 24 group II Clostridium botulinum strains. Genetic diversity of the strains was revealed by amplified fragment length polymorphism (AFLP) analysis. The minimum growth temperatures ranged from 6.2 to 8.6 degrees C, and the maximum growth temperatures ranged from 34.7 to 39.9 degrees C. The mean maximum growth temperatures and mean maximum growth rates of type E strains at 37 degrees C were significantly higher than those of type B and type F strains. A significant correlation between maximum growth rates at 37 degrees C and maximum growth temperatures was found for all strains. Some type E strains with a high minimum growth temperature also had a higher maximum growth rate at 37 degrees C than at 30 degrees C, which suggests that some group II C. botulinum strains are more mesophilic in their growth properties than others. We found relatively small differences between AFLP clusters, indicating that diverse genetic background among the strains was not reflected in the growth properties. The growth characteristics of group II C. botulinum and some type E strains with mesophilic growth properties may have an impact on inoculation studies and predictive modeling for assessing the safety of foods. PMID- 22054180 TI - Effect of pH and water activity on the growth limits of Listeria monocytogenes in a cheese matrix at two contamination levels. AB - Listeria monocytogenes can proliferate at the beginning of cheesemaking as the conditions favor growth. The objective of this study was to establish the growth limits of L. monocytogenes in a cheese matrix, in case of potential contamination of the milk prior to cheese manufacture. A semisoft laboratory scale model cheese system was made at different initial pH and water activity (a(w)) levels with a mix of two strains of L. monocytogenes. A factorial design of five pH values (5.6 to 6.5), four a(w) values (0.938 to 0.96), and two L. monocytogenes inoculation levels (1 to 20 CFU/ml and 500 to 1,000 CFU/ml) was carried out. Each combination was evaluated in six independent replicates. In order to determine if there was a dominant strain, isolated colonies from the cheeses were analyzed by pulsed-field gel electrophoresis. The data relating to growth initiation were fitted to a logistic regression model. The a(w) of milk influenced the probability of growth initiation of L. monocytogenes at both low and high contamination levels. The pH, at the concentrations tested, had a lower effect on the probability of growth initiation. At pH 6.5 and a(w) of 0.99 for low contamination levels and pH 6.5 and a(w) of 0.97 for high contamination levels, increases in population of up to 4 and 2 log were observed at low and high contamination levels, respectively. This shows that if conditions are favorable for growth initiation at the early stages of the cheesemaking process, contamination of milk, even with low numbers, could lead to L. monocytogenes populations that exceed the European Union's microbiological limit of 100 CFU/g of cheese. PMID- 22054181 TI - A systematic review and meta-analysis of the effects of pasteurization on milk vitamins, and evidence for raw milk consumption and other health-related outcomes. AB - Pasteurization of milk ensures safety for human consumption by reducing the number of viable pathogenic bacteria. Although the public health benefits of pasteurization are well established, pro-raw milk advocate organizations continue to promote raw milk as "nature's perfect food." Advocacy groups' claims include statements that pasteurization destroys important vitamins and that raw milk consumption can prevent and treat allergies, cancer, and lactose intolerance. A systematic review and meta-analysis was completed to summarize available evidence for these selected claims. Forty studies assessing the effects of pasteurization on vitamin levels were found. Qualitatively, vitamins B12 and E decreased following pasteurization, and vitamin A increased. Random effects meta-analysis revealed no significant effect of pasteurization on vitamin B6 concentrations (standardized mean difference [SMD], -2.66; 95% confidence interval [CI], -5.40, 0.8; P = 0.06) but a decrease in concentrations of vitamins B1 (SMD, -1.77; 95% CI, -2.57, -0.96; P < 0.001), B2 (SMD, -0.41; 95% CI, -0.81, -0.01; P < 0.05), C (SMD, -2.13; 95% CI, -3.52, -0.74; P < 0.01), and folate (SMD, -11.99; 95% CI, 20.95, -3.03; P < 0.01). The effect of pasteurization on milk's nutritive value was minimal because many of these vitamins are naturally found in relatively low levels. However, milk is an important dietary source of vitamin B2, and the impact of heat treatment should be further considered. Raw milk consumption may have a protective association with allergy development (six studies), although this relationship may be potentially confounded by other farming-related factors. Raw milk consumption was not associated with cancer (two studies) or lactose intolerance (one study). Overall, these findings should be interpreted with caution given the poor quality of reported methodology in many of the included studies. PMID- 22054182 TI - Control of Salmonella enterica Typhimurium in chicken breast meat by irradiation combined with modified atmosphere packaging. AB - Salmonella is one of the leading causes of human foodborne illnesses originating from meat and poultry products. Cross-contamination of Salmonella from raw to cooked products continues to be problematic in the food industry. Therefore, new intervention strategies are needed for meat and poultry products. Vacuum or modified atmosphere packaging (MAP) are common packaging techniques used to extend the shelf life of meat products. Irradiation has been well established as an antibacterial treatment to reduce pathogens on meat and poultry. Combining irradiation with high-CO(2)+CO MAP was investigated in this study for improving the control of Salmonella enterica Typhimurium on chicken breast meat. The radiation sensitivities (D10-values) of this pathogen in chicken breast meat were found to be similar in vacuum and in high-CO(2)+CO MAP (0.55 +/- 0.03 kGy and 0.54 +/- 0.03 kGy, respectively). Irradiation at 1.5 kGy reduced the Salmonella population by an average of 3 log. Some Salmonella cells survived in both vacuum and high-CO(2) + CO MAP through 6 weeks of refrigerated storage following irradiation. This pathogen also grew in both vacuum and MAP when the product was held at 25 degrees C. This study demonstrated that irradiation is an effective means of reducing Salmonella on meat or poultry, but packaging in either vacuum or MAP had little impact during subsequent refrigerated storage. PMID- 22054183 TI - Comparison of reduction in foodborne viral surrogates by high pressure homogenization. AB - With the increasing global spread of human noroviral infections and the emergence of highly virulent noroviral strains, novel inactivation methods are needed to control foodborne outbreaks. High pressure homogenization (HPH) is a novel method that can be applied for foodborne virus reduction in fluids being continuously processed. Our objective in the present study was to compare the titer reduction by HPH between feline calicivirus strain F9 (FCV-F9) and murine norovirus 1 (MNV 1) as surrogates for human noroviruses, and MS2 (single-stranded F-RNA coliphage) and somatic coliphage phiX174 (single-stranded DNA) as indicators of fecal contamination. Duplicate experiments with each virus in phosphate-buffered saline were carried out with homogenization pressures of 0, 100, 200, 250, and 300 MPa, with exposure temperatures of 24, 46, 63, 70, and 75 degrees C, respectively, for <2 s. FCV-F9 was found highly susceptible to HPH treatment pressures of 300 MPa, with a reduction of >4.95 log PFU/ml. Lower pressures of 250, 200, and 100 MPa resulted in reductions of 1.61, 0.60, and 0.18 log PFU/ml of FCV-F9, respectively, while MNV-1 was not reduced at these lower pressures. Coliphage phiX174 showed no significant reduction at 300 MPa or lower homogenization pressures in comparison with MS2, which did show 3.3-log PFU/ml reduction at 300 MPa. Future studies using juices for industrial application of HPH to determine microbial inactivation with simultaneous retention of sensory and nutritional value of foods are needed. PMID- 22054184 TI - Evaluation of murine norovirus persistence in environments relevant to food production and processing. AB - Human norovirus (NoV) causes outbreaks of acute gastroenteritis associated with many ready-to-eat foods, including fresh produce. Effective inactivation procedures must consider virus survival under conditions of produce production and processing. This study aimed to investigate the persistence of NoV in a variety of environments, using murine NoV (MNV) as a surrogate for NoV. MNV was incubated for up to 42 days at room temperature on stainless steel disks, on lettuce, on soil, and in potable water and titers determined by plaque assay. A 1 log reduction of MNV infectivity was observed after 29 days in water, 4 days on lettuce, 12 days on soil, and 15 days on stainless steel disks. MNV survived longer in water than in any of the other environments, indicating that drying may contribute to NoV inactivation. MNV genomes were not significantly reduced for up to 42 days, suggesting that genomic detection is not a reliable indicator of viability. Overall, our findings provide valuable information regarding the potential for NoV transmission in the food supply. PMID- 22054185 TI - Comparison of virulence and antibiotic resistance genes of food poisoning outbreak isolates of Staphylococcus aureus with isolates obtained from bovine mastitis milk and pig carcasses. AB - Staphylococcus aureus is the etiological agent in a variety of infections in humans and livestock and produces enterotoxins leading to staphylococcal food poisoning (SFP), one of the most prevalent foodborne intoxication diseases worldwide. Pork and bovine milk are considered possible sources of SFP because pig skin is often colonized by S. aureus and bovine mastitis caused by S. aureus is common, but conclusive data are limited. The objective of the present study was to compare S. aureus isolates associated with cases of SFP with isolates obtained from bovine mastitis milk and pig carcasses. DNA microarray analysis and spa gene typing were performed with 100 S. aureus isolates: 20 isolates related to outbreaks of SFP in humans, 39 isolates obtained from pig carcasses, and 41 isolates collected from bovine mastitis milk. No overlap in spa types was observed for SFP isolates (t008, t015, t018, t024, t056, t084, t279, t377, t383, t648, t733, t912, t1239, t1270, t4802, and t6969) and isolates gathered from milk or pork. The porcine isolates were assigned to t034, t208, t337, t524, t899, t1939, t2922, t2971, t4475, and t7006, and the bovine isolates belonged to t267, t524, t529, t1403, t2953, t7007, t7008, and t7013. Comparison of microarray profiles revealed similar virulence gene patterns for isolates collected from the same host (pigs or cattle) but few similarities between SFP isolate profiles and the profiles of isolates obtained from bovine mastitis milk and pig carcasses. Although only some bovine and porcine isolates possessed the beta-lactamase gene blaZ (milk, 24%; pork, 28%), significantly higher numbers of SFP isolates contained blaZ (90%). Investigations of these isolates provided no evidence that pork or bovine mastitis milk represent common sources of SFP. PMID- 22054186 TI - Comparison of public health impact of Listeria monocytogenes product-to-product and environment-to-product contamination of deli meats at retail. AB - This study compared the relative public health impact in deli meats at retail contaminated with Listeria monocytogenes by either (i) other products or (ii) the retail environment. Modeling was performed using the risk of listeriosis associated deaths as a public health outcome of interest and using two deli meat products (i.e., ham and turkey, both formulated without growth inhibitors) as model systems. Based on reported data, deli meats coming to retail were assumed to be contaminated at a frequency of 0.4%. Three contamination scenarios were investigated: (i) a baseline scenario, in which no additional cross contamination occurred at retail, (ii) a scenario in which an additional 2.3% of products were cross-contaminated at retail due to transfer of L. monocytogenes cells from already contaminated ready-to-eat deli meats, and (iii) a scenario in which an additional 2.3% of products were contaminated as a result of cross contamination from a contaminated retail environment. By using a previously reported L. monocytogenes risk assessment model that uses product-specific growth kinetic parameters, cross-contamination of deli ham and turkey was estimated to increase the relative risk of listeriosis-associated deaths by 5.9- and 6.1-fold, respectively, for contamination from other products and by 4.9- and 5.8-fold, respectively, for contamination from the retail environment. Sensitivity and scenario analyses indicated that the frequency of cross-contamination at retail from any source (other food products or environment) was the most important factor affecting the relative risk of listeriosis-associated deaths. Overall, our data indicate that retail-level cross-contamination of ready-to-eat deli meats with L. monocytogenes has the potential to considerably increase the risk of human listeriosis cases and deaths, and thus precise estimates of cross contamination frequency are critical for accurate risk assessments. PMID- 22054187 TI - Designing a national restaurant inspection disclosure system for New Zealand. AB - The World Health Organization estimates that up to 30% of individuals in developed countries become ill from contaminated food or water each year, and up to 70% of these illnesses are estimated to be linked to food service facilities. The aim of restaurant inspections is to reduce foodborne outbreaks and enhance consumer confidence in food service. Inspection disclosure systems have been developed as tools for consumers and incentives for food service operators. Disclosure systems are common in developed countries but are inconsistently used, possibly because previous research has not determined the best format for disclosing inspection results. This study was conducted to develop a consistent, compelling, and trusted inspection disclosure system for New Zealand. Existing international and national disclosure systems were evaluated. Two cards, a letter grade (A, B, C, or F) and a gauge (speedometer style), were designed to represent a restaurant's inspection result and were provided to 371 premises in six districts for 3 months. Operators (n = 269) and consumers (n = 991) were interviewed to determine which card design best communicated inspection results. Less than half of the consumers noticed cards before entering the premises; these data indicated that the letter attracted more initial attention (78%) than the gauge (45%). Fifty-eight percent (38) of the operators with the gauge preferred the letter; and 79% (47) of the operators with letter preferred the letter. Eighty-eight percent (133) of the consumers in gauge districts preferred the letter, and 72% (161) of those in letter districts preferring the letter. Based on these data, the letter method was recommended for a national disclosure system for New Zealand. PMID- 22054188 TI - A meta-analysis of the published literature on the effectiveness of antimicrobial soaps. AB - The goal of this research was to conduct a systematic quantitative analysis of the existing data in the literature in order to determine if there is a difference between antimicrobial and nonantimicrobial soaps and to identify the methodological factors that might affect this difference. Data on hand washing efficacy and experimental conditions (sample size, wash duration, soap quantity, challenge organism, inoculum size, and neutralization method) from published studies were compiled and transferred to a relational database. A total of 25 publications, containing 374 observations, met the study selection criteria. The majority of the studies included fewer than 15 observations with each treatment and included a direct comparison between nonantimicrobial soap and antimicrobial soap. Although differences in efficacy between antimicrobial and nonantimicrobial soap were small (~0.5-log CFU reduction difference), antimicrobial soap produced consistently statistically significantly greater reductions. This difference was true for any of the antimicrobial compounds investigated where n was >20 (chlorhexidine gluconate, iodophor, triclosan, or povidone). Average log reductions were statistically significantly greater (~2 log CFU) when either gram positive or gram-negative transient organisms were deliberately added to hands compared with experiments done with resident hand flora (~0.5 log CFU). Our findings support the importance of using a high initial inoculum on the hands, well above the detection limit. The inherent variability in hand washing seen in the published literature underscores the importance of using a sufficiently large sample size to detect differences when they occur. PMID- 22054189 TI - Development of a PCR-restriction fragment length polymorphism protocol for rapid detection and differentiation of four cockroach vectors (group I "Dirty 22" species) responsible for food contamination and spreading of foodborne pathogens: public health importance. AB - Assessing the adulteration of food products and the presence of filth and extraneous materials is one of the measures that the U.S. Food and Drug Administration (FDA) utilizes in implementing regulatory actions of public health importance. To date, 22 common pest species (also known as the "Dirty 22" species) have been regarded by this agency as the spreaders of foodborne diseases. We have further categorized the Dirty 22 species into four groups: I has four cockroach species, II has two ant species, III has 12 fly species, and IV has four rodent species. The presence of any Dirty 22 species is also considered an indicator of unsanitary conditions in food processing and storage facilities. In this study, we describe the development of a two-step nested PCR protocol to amplify the small subunit ribosomal gene of group I Dirty 22 species that include four cockroach species: Blattella germanica, Blatta orientalis, Periplaneta americana, and Supella longipalpa, along with the development of a PCR-restriction fragment length polymorphism method for rapid detection and differentiation of these violative species. This method will be utilized when the specimen cannot be identified with conventional microscopic taxonomic methods, especially when only small body parts are separated and recovered from food samples for analysis or when these body parts are in a decomposed state. This new PCR-restriction fragment length polymorphism will provide correct identification of group I Dirty 22 species; this information can then be used in regulation and prevention of foodborne pathogens. PMID- 22054190 TI - Effect of photocatalytic and hydrophobic coatings on brewery surface microorganisms. AB - The aim of this study was to determine whether process hygiene in the beverage industry could be improved by applying new coating techniques to process surfaces. Photocatalytic titanium dioxide (TiO(2)) and hydrophobic coatings applied to stainless steel with or without added antimicrobial compounds were studied in laboratory attachment tests and in a 15-month process study. No clear reductions in numbers of attached microbes were obtained with photocatalytic coatings, except for coatings to which silver had been added. These TiO(2)+Ag coatings reduced microbial coverage in laboratory studies and in some process samples. Hydrophobic coatings reduced the area coverage of microorganisms in 4-h laboratory studies but did not affect colony counts in laboratory or process studies. The surfaces had changed from hydrophobic into hydrophilic during the process study. The coatings did not mechanically fully withstand process conditions; part of the hydrophobic coatings had peeled off, most of the precipitated Ag had dissolved, and some of the TiO(2) coatings were damaged. In conclusion, functional coatings have potential for reducing microbial loads on beverage industry surfaces, but these coatings need further development. PMID- 22054191 TI - High salinity relay as a postharvest processing strategy to reduce vibrio vulnificus levels in Chesapeake Bay oysters (Crassostrea virginica). AB - In 2009 the U.S. Food and Drug Administration (FDA) announced its intention to implement postharvest processing (PHP) methods to eliminate Vibrio vulnificus from oysters intended for the raw, half-shell market that are harvested from the Gulf of Mexico during warmer months. FDA-approved PHP methods can be expensive and may be associated with unfavorable responses from some consumers. A relatively unexplored PHP method that uses relaying to high salinity waters could be an alternative strategy, considering that high salinities appear to negatively affect the survival of V. vulnificus. During relay, however, oysters may be exposed to rapid and large salinity increases that could cause increased mortality. In this study, the effectiveness of high salinity relay to reduce V. vulnificus to <30 most probable number (MPN) per g and the impact on oyster mortality were assessed in the lower Chesapeake Bay. Two relay experiments were performed during the summer and fall of 2010. Oysters collected from three grow out sites, a low salinity site (14 to 15 practical salinity units [psu]) and two moderate salinity sites (22 to 25 psu), were relayed directly to a high salinity site (>=30 psu) on Virginia's Eastern Shore. Oysters were assayed for V. vulnificus and Vibrio parahaemolyticus (another Vibrio species of concern) densities at time 0 prior to relay and after 7 and 14 days of relay, using the FDA MPN enrichment method combined with detection by real-time PCR. After 14 days, both V. vulnificus and V. parahaemolyticus densities were <=0.8 MPN/g, and decreases of 2 to 3 log in V. vulnificus densities were observed. Oyster mortalities were low (<=4%) even for oysters from the low salinity harvest site, which experienced a salinity increase of approximately 15 psu. Results, although preliminary and requiring formal validation and economic analysis, suggest that high salinity relay could be an effective PHP method. PMID- 22054192 TI - Effect of wash treatments on reducing human norovirus on iceberg lettuce and perilla leaf. AB - Human noroviruses (NoVs) are major causes of nonbacterial gastroenteritis; they are transmitted by food and water, as well as person-to-person. The consumption of contaminated raw or uncooked food such as vegetables and fruits has been identified as a common source of human NoV outbreaks. In an effort to understand the survival and persistence of human NoVs on fresh produce, the efficacy of washing treatments in the removal of human NoVs from vegetables was evaluated. This study used artificially contaminated vegetables (iceberg lettuce and perilla leaf), and washing was done with tap water for convenience. Wash treatments included immersion in water, rinsing with running water, and a combination of immersion and rinsing (treatments I to III, respectively). The effect of a class I detergent, a commercial product used for washing fruits and vegetables, was also evaluated (treatment IV). After the wash treatments, the remnants of human NoVs on samples were measured via real-time reverse transcriptase PCR. The results varied among treatments and by vegetable. For iceberg lettuce, a reduction of 0.9 log was noted in the treatment III group. The wash treatment was more effective in the perilla leaf samples: each treatment significantly reduced the numbers of human NoVs (0.69- to 1.29-log reduction). These data demonstrated that wash treatments reduced numbers of virus from the surfaces of the vegetables. Therefore, washing would seem to be a basic step in reducing numbers of virus in food preparation and in viral transmission routes. PMID- 22054193 TI - Prevalence of Campylobacter and Salmonella in raw chicken on retail sale in the republic of Ireland. AB - To assess the current risks to consumers from Campylobacter and Salmonella in raw chicken products sold in the Republic of Ireland, a retail survey was undertaken to define their prevalence. Samples (n = 510) were analyzed using protocols based on ISO 10272-1:2006 and ISO 6579:2002. Processor codes on pack labels showed that 67% of samples were produced in the Republic of Ireland and 25% in the United Kingdom. Salmonella was present in 5.1% of samples, but the eight serovars found caused less than 7% of human salmonellosis reported in the Republic of Ireland. The results suggest that on-farm controls to limit Salmonella infection of broilers have been successful and that in Ireland raw chicken is not a significant cause of salmonellosis in humans. The overall prevalence of Campylobacter spp. was 84.3%. Isolation by the ISO method found 52.7% of samples to be positive, but overgrowth by contaminants was frequently evident. Therefore, in addition to enrichment, an homogenized sample was plated directly onto modified charcoal cefoperazone deoxycholate agar, and this detected a further 31.6%. Speciation of isolates (n = 426) determined that 67% were Campylobacter jejuni and 32% were Campylobacter coli. These species are the most common cause of campylobacteriosis in man. The results indicate that there is a need for poultry producers to introduce interventions to minimize the exposure of consumers in the Republic of Ireland to Campylobacter spp., as has been successfully done for Salmonella. PMID- 22054194 TI - Escherichia coli O157:H7 populations in ruminants can be reduced by orange peel product feeding. AB - Foodborne pathogenic bacteria such as Escherichia coli O157:H7 are threats to the safety of beef. Citrus peel and dried orange pulp are by-products from citrus juice production that have natural antimicrobial effects and are often incorporated into least-cost ration formulations for beef and dairy cattle. This study was designed to determine if orange peel and pulp affected E. coli O157:H7 populations in vivo. Sheep (n = 24) were fed a cracked corn grain-based diet that was supplemented with a 50-50 mixture of dried orange pellet and fresh orange peel to achieve a final concentration (dry matter basis, wt/wt) of 0, 5, or 10% pelleted orange peel (OP) for 10 days. Sheep were artificially inoculated with 10(10) CFU of E. coli O157:H7 by oral dosing. Fecal shedding of E. coli O157:H7 was measured daily for 5 days after inoculation, after which all animals were humanely euthanized. At 96 h postinoculation, E. coli O157:H7 shedding was reduced (P < 0.05) in sheep fed 10% OP. Populations of inoculated E. coli O157:H7 were reduced by OP treatment throughout the gastrointestinal tract; however, this reduction reached significant levels in the rumen (P < 0.05) of sheep fed 10% OP diets. Cecal and rectal populations of E. coli O157:H7 were reduced (P < 0.05) by inclusion of both 5 and 10% OP diets. Our results demonstrate that orange peel products can be used as a preharvest intervention strategy as part of an integrated pathogen reduction scheme. PMID- 22054195 TI - Consumer food safety perceptions and practices in a Turkish community. AB - Research has shown that most reported foodborne outbreaks are caused by food prepared and consumed at home, thus emphasizing the importance of consumer food safety knowledge. In this study, 2,000 randomly selected residents from Canakkale, Turkey, participated in face-to-face interviews to assess their food safety perceptions and practices. Questions covered the attention given to expiration dates, safety certificates, and food additives during shopping; consumption of high-risk foods; safe food handling; storage knowledge; and their source of food safety knowledge. Statistical analyses were done to clarify the differences according to three main aspects: gender, age, and educational level. Results showed that women and middle-aged respondents were significantly more careful during shopping and more interested in food safety issues than men and younger individuals. A significant relationship was found between gender and consumption of high-risk foods, with men consuming more of these foods than women. Furthermore, high-risk foods were more frequently consumed by young participants than by older participants, with more highly educated consumers shopping more consciously. Although most respondents appeared to know proper food handling and storage practices, almost all participants lacked some information on some issues. In order to remove these deficiencies, a brochure was prepared and distributed to people in various parts of the city. In addition, public seminars were organized. However, to ensure that this information results in positive attitude and behavioral changes, seminars should be repeated at specific intervals, and education procedures and processes should be controlled regularly. PMID- 22054196 TI - Comparison of automated BAX PCR and standard culture methods for detection of Listeria monocytogenes in blue Crabmeat (Callinectus sapidus) and blue crab processing plants. AB - This study compared the automated BAX PCR with the standard culture method (SCM) to detect Listeria monocytogenes in blue crab processing plants. Raw crabs, crabmeat, and environmental sponge samples were collected monthly from seven processing plants during the plant operating season, May through November 2006. For detection of L. monocytogenes in raw crabs and crabmeat, enrichment was performed in Listeria enrichment broth, whereas for environmental samples, demi Fraser broth was used, and then plating on both Oxford agar and L. monocytogenes plating medium was done. Enriched samples were also analyzed by BAX PCR. A total of 960 samples were examined; 59 were positive by BAX PCR and 43 by SCM. Overall, there was no significant difference (P <= 0.05) between the methods for detecting the presence of L. monocytogenes in samples collected from crab processing plants. Twenty-two and 18 raw crab samples were positive for L. monocytogenes by SCM and BAX PCR, respectively. Twenty and 32 environmental samples were positive for L. monocytogenes by SCM and BAX PCR, respectively, whereas only one and nine finished products were positive. The sensitivities of BAX PCR for detecting L. monocytogenes in raw crabs, crabmeat, and environmental samples were 59.1, 100, and 60%, respectively. The results of this study indicate that BAX PCR is as sensitive as SCM for detecting L. monocytogenes in crabmeat, but more sensitive than SCM for detecting this bacterium in raw crabs and environmental samples. PMID- 22054197 TI - Evaluation of modified moore swabs and continuous flow centrifugation for concentration of Salmonella and Escherichia coli O157:H7 from large volumes of water. AB - Modified Moore swabs (MMS; consisting of a polyvinyl chloride cartridge filled with gauze) capture microorganisms within the packed gauze as water flows through the cartridge, while continuous flow centrifugation (CFC) uses centrifugation to sediment the microorganisms while water continuously flows in the system. This study evaluated and compared the efficacy of MMS and CFC for concentration and subsequent detection of Escherichia coli O157:H7 and Salmonella from large volumes of water (10 liters). Water samples were spiked at levels of 10(1), 10(2), 10(3), and 10(4) CFU/100 ml with three-strain cocktails of either E. coli O157:H7 or Salmonella serovars, which had been previously transformed with a plasmid to express resistance to ampicillin as well as green, red, or cyan fluorescent proteins. Plating was performed before and after concentration on tryptic soy agar supplemented with ampicillin in order to quantitate the concentration efficiencies of each method. The two lowest spiking levels were also enriched in low volumes of tryptic soy broth supplemented with ampicillin followed by testing via lateral flow devices. Significant (P < 0.05) concentrations of initial levels of E. coli O157:H7 in the range of 0.7 to 1.0 and 1.2 to 1.4 log were achieved within approximately 35 min of processing time via MMS and CFC, respectively. Similarly, significant (P < 0.05) concentrations were also achieved for Salmonella with 0.9 to 1.2 and 1.2 to 1.4 log concentration for MMS and CFC, respectively. There were no statistical differences (P > 0.05) between the two concentration methods in their ability to concentrate either of the two target bacteria. Significantly (P > 0.05) more spiked samples were detected by lateral flow devices following concentration and enrichment than for nonconcentrated, enriched samples. It is concluded that both MMS and CFC have potential to be used to enhance the sensitivity of downstream bacterial detection methods used to test irrigation water for the presence of foodborne pathogens. PMID- 22054198 TI - Trace elements and metals in farmed sea bass and gilthead bream from Tenerife Island, Spain. AB - The aim of this study was to determine the levels of metals (Ca, K, Na, Mg) and trace metals (Ni, Fe, Cu, Mn, Zn, Pb, Cd) in two fish species (gilthead bream [Sparus aurata] and sea bass [Dicentrarchus labrax]) collected from fish farms located along the coast of Tenerife Island. Ca, K, Na, Mg, Fe, Cu, Zn, and Mn were measured by flame atomic absorption spectrometry, whereas Pb, Cd, and Ni were determined using graphite furnace atomic absorption spectrometry. Mean Fe, Cu, Mn, and Zn contents were 3.09, 0.59, 0.18, and 8.11 mg/kg (wet weight) in S. aurata and 3.20, 0.76, 0.24, and 10.11 mg/kg (wet weight) in D. labrax, respectively. In D. labrax, Ca, K, Na, and Mg levels were 1,955, 2,787, 699.7, and 279.2 mg/kg (wet weight), respectively; in S. aurata, they were 934.7, 3,515, 532.8, and 262.8 mg/kg (wet weight), respectively. The Pb level in S. aurata was 7.28 +/- 3.64 MUg/kg (wet weight) and, in D. labrax, 4.42 +/- 1.56 MUg/kg (wet weight). Mean Cd concentrations were 3.33 +/- 3.93 and 1.36 +/- 1.53 MUg/kg (wet weight) for D. labrax and S. aurata, respectively. All Pb and Cd levels measured were well below the accepted European Commission limits, 300 and 50 MUg/kg for lead and cadmium, respectively. PMID- 22054199 TI - Foodborne illness associated with Cryptosporidium and Giardia from livestock. AB - Waterborne outbreaks caused by Cryptosporidium and Giardia are well documented, while the public health implications for foodborne illness from these parasites have not been adequately considered. Cryptosporidium and Giardia are common in domestic livestock, where young animals can have a high prevalence of infection, shedding large numbers of oocysts and cysts. Molecular epidemiological studies have advanced our knowledge on the distribution of Cryptosporidium and Giardia species and genotypes in specific livestock. This has enabled better source tracking of contaminated foods. Livestock generate large volumes of fecal waste, which can contaminate the environment with (oo)cysts. Evidence suggests that livestock, particularly cattle, play a significant role in food contamination, leading to outbreaks of cryptosporidiosis. However, foodborne giardiasis seems to originate primarily from anthroponotic sources. Foodborne cryptosporidiosis and giardiasis are underreported because of the limited knowledge of the zoonotic potential and public health implications. Methods more sensitive and cheaper are needed to detect the often-low numbers of (oo)cysts in contaminated food and water. As the environmental burden of Cryptosporidium oocysts and Giardia cysts from livestock waste increases with the projected increase in animal agriculture, public health is further compromised. Contamination of food by livestock feces containing Cryptosporidium oocysts and Giardia cysts could occur via routes that span the entire food production continuum. Intervention strategies aimed at preventing food contamination with Cryptosporidium and Giardia will require an integrated approach based on knowledge of the potential points of entry for these parasites into the food chain. This review examines the potential for foodborne illness from Cryptosporidium and Giardia from livestock sources and discusses possible mechanisms for prevention and control. PMID- 22054200 TI - Food safety objective approach for controlling Clostridium botulinum growth and toxin production in commercially sterile foods. AB - As existing technologies are refined and novel microbial inactivation technologies are developed, there is a growing need for a metric that can be used to judge equivalent levels of hazard control stringency to ensure food safety of commercially sterile foods. A food safety objective (FSO) is an output-oriented metric that designates the maximum level of a hazard (e.g., the pathogenic microorganism or toxin) tolerated in a food at the end of the food supply chain at the moment of consumption without specifying by which measures the hazard level is controlled. Using a risk-based approach, when the total outcome of controlling initial levels (H(0)), reducing levels (SigmaR), and preventing an increase in levels (SigmaI) is less than or equal to the target FSO, the product is considered safe. A cross-disciplinary international consortium of specialists from industry, academia, and government was organized with the objective of developing a document to illustrate the FSO approach for controlling Clostridium botulinum toxin in commercially sterile foods. This article outlines the general principles of an FSO risk management framework for controlling C. botulinum growth and toxin production in commercially sterile foods. Topics include historical approaches to establishing commercial sterility; a perspective on the establishment of an appropriate target FSO; a discussion of control of initial levels, reduction of levels, and prevention of an increase in levels of the hazard; and deterministic and stochastic examples that illustrate the impact that various control measure combinations have on the safety of well-established commercially sterile products and the ways in which variability all levels of control can heavily influence estimates in the FSO risk management framework. This risk-based framework should encourage development of innovative technologies that result in microbial safety levels equivalent to those achieved with traditional processing methods. PMID- 22054201 TI - Real-time dominant frequency analysis of the pulmonary vein in patients with paroxysmal atrial fibrillation. AB - BACKGROUND: Paroxysmal atrial fibrillation (PAF) can be treated with pulmonary vein isolation (PVI). A spectral analysis can identify sites of high-frequency activity during atrial fibrillation (AF). We investigated the role of the PVs on AF perpetuation by dominant frequency (DF) analysis. METHODS: Thirty-one consecutive patients with PAF who underwent PVI were included in the prospective study. DF was calculated in each of the PVs, 16, five, and five sites in the left atrium, the coronary sinus, and the right atrium, respectively. In patients presenting sinus rhythm at the baseline, AF was induced by pacing. The PVs were then divided into two groups; PVs demonstrated the highest DF (HDF-PV) and others. RESULTS: One patient was excluded from the analysis because sustained AF could not be induced. AF was terminated in 43.3% (13/30) of patients during ablation. Of 92 PVs isolated during AF, 30 and 62 PVs were classified into the HDF-PV and others, respectively. PAF was more frequently terminated by the HDF-PV isolation compared to the others (33.3% [10/30] vs 4.8% [3/62], P = 0.0004). Interestingly, nine of the 30 HDF-PVs showing the highest DF among all 30 regions, including extra PVs, led to AF termination in 88.9% (eight out of nine) of cases. Moreover, the HDF-PVs isolation resulted in a greater AF cycle length prolongation than the other PVs isolation (12.1+/-5.0 vs 2.7+/-7.6 ms, P = 0.007). CONCLUSION: Termination of PAF was more frequently observed during ablation of the PVs with the highest DF. The PV showing high DF played an important role in the maintenance of PAF. PMID- 22054202 TI - Endogenous plasma erythropoietin, cardiovascular mortality and all-cause mortality in renal transplant recipients. AB - Cardiovascular disease (CVD) is the main cause of mortality in renal transplant recipients (RTR). Classical factors only partly explain the excess risk. We hypothesized that high EPO--a marker for inflammation, angiogenesis and hypoxia- is associated with CVD in RTR. A total of 568 RTR (51+/-12 years; 45% female; creatinine clearance (CrCl) 57+/-20 mL/min/1.73 m(2)) were included at median 6 [IQR 3-11] years after transplantation. Subjects on exogenous EPO and ferritin depleted subjects were excluded. Median EPO level was 17.3 [IQR 11.9-24.2] IU/L. Gender-stratified tertiles of age-corrected EPO were positively associated with waist circumference (but not BMI), CVD history, time since transplantation, diuretics, azathioprine, CRP, mean corpuscular volume and triglyceride levels, and inversely with CrCl, RAAS-inhibition, cyclosporine, hemoglobin, total- and HDL-cholesterol. During follow-up for 7 [6-7] years, 121 RTR (21%) died, 64 of cardiovascular (CV) causes. Higher EPO (per 10 IU/L) was associated with total (HR1.16 [1.04-1.29], p = 0.01) and CV mortality (HR1.22 [1.06-1.40], p = 0.005), independent of age, gender, hemoglobin, inflammation, renal function and Framingham risk factors. Thus, EPO and mortality are linked in RTR, independent of potential confounders. This suggests that yet other mechanisms are involved. Dissecting determinants of EPO in RTR may improve understanding of mechanisms behind excess CV risk in this population. PMID- 22054203 TI - Early surgical laser-assisted management of bisphosphonate-related osteonecrosis of the jaws (BRONJ): a retrospective analysis of 101 treated sites with long-term follow-up. AB - BACKGROUND DATA: The management of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is still controversial. OBJECTIVE: The purpose of this study was to compare surgical and nonsurgical approaches to the treatment of BRONJ and the possible usefulness of Nd:YAG and Er:YAG lasers. METHODS: One hundred and twenty eight patients (33 males, 95 females; 52 with diagnosis of multiple myeloma, 53 with diagnosis of bone metastasis, and 23 with diagnosis of osteoporosis) affected by BRONJ were evaluated at the Unit of Oral Pathology and Medicine and Laser-Assisted Surgery of the University of Parma, Italy, between January 2004 and July 2009. Overall number of BRONJ sites was 151, and number of treated sites was 101. In order to assess the efficacy of different treatments, sites were subclassified as follows: Group 1 (G1): 12 sites treated with medical therapy; Group 2 (G2): 27 sites treated with medical therapy associated with low level laser therapy (LLLT); Group 3 (G3): 17 sites treated with a combination of medical and surgical therapy; Group 4 (G4): 45 sites treated with a combination of medical therapy, surgical (including laser-assisted) therapy, and LLLT. Outcome of treatment was assessed using the staging system proposed by Ruggiero et al. Transition from a higher stage to a lower one for at least 6 months was considered as clinical improvement and suggestive of a successful treatment. RESULTS: Clinical improvement was achieved in 3 out of 12 (25%) BRONJ sites in G1. Sites if G2 with an improvement were 18 out of 27 (66%). Nine out 17 BRONJ sites (53%) in G3 had a transition to a lower stage after treatment. For sites in G4, a clinical improvement was recorded in 40 out of 45 cases (89%). CONCLUSIONS: In our experience, the percentage of success obtained with a combined approach based on medical therapy, surgical (including laser-assisted) therapy, and LLLT (G4) is significantly higher than the percentage of improvement obtained in G1, G2, and G3. PMID- 22054204 TI - Vitiligo treatment with monochromatic excimer light and tacrolimus: results of an open randomized controlled study. AB - BACKGROUND DATA: Narrow band ultraviolet B (UVB) is an effective and safe option for the treatment of vitiligo. However, a complete and long-lasting repigmention of vitiligo patches is difficult to achieve. Combined treatments with novel sources of phototherapy and topical agents represent possible new strategies. OBJECTIVE: The purpose of this study was to compare the efficacy of combined tacrolimus and 308-nm excimer light (MEL) vs 308-nm MEL monotherapy in treating vitiligo in a controlled study. METHODS: Fifty-three patients affected by vitiligo were enrolled in this open prospective study. Patients were divided into three groups: Group I included 20 patients treated with MEL 308 nm twice weekly and oral vitamin E; Group II included 20 patients treated with MEL 308 nm twice weekly combined with 0.1% tacrolimus once a day and oral vitamin E; and Group III included 13 patients treated only with oral vitamin E. Efficacy was assessed at the end of 12 weeks based on the percentage of repigmentation. RESULTS: Fifty-two patients completed 12 weeks of treatment. Group I (MEL + vitamin E) showed a moderate repigmentation in 35% of patients, good repigmentation in 30%, excellent repigmentation in 25%, and poor repigmentation in 10%; Group II (MEL + tacrolimus 0.1%+ vitamin E) presented moderate repigmentation in 25% of patients, good repigmentation in 40%, excellent repigmentation in 30%, and poor repigmentation in 5%; Group III (vitamin E) showed moderate repigmentation in 16% and 84% did not show signs of repigmentation. CONCLUSIONS: Our results demonstrate that the combination treatment of 0.1% tacrolimus ointment plus 308-nm MEL and 308-nm MEL monotherapy are effective, safe, and well tolerated for the treatment of vitiligo compared to treatment with vitamin E. Furthermore, this study suggests that an association with topical immunomodulators could enhance the clinical response in vitiligo, especially in more resistant anatomical sites. PMID- 22054205 TI - Medication quality and quality of life in the elderly, a cohort study. AB - BACKGROUND: Modern drugs have made large contributions to better health and quality of life. Increasing proportions of negative side effects due to extensive pharmacological treatment are however observed especially among elderly patients who have multiple health problems. The aim of our study was to see if there is an association between medication quality and quality of life. METHODS: 150 patients discharged from hospital. Inclusion criteria were: living in ordinary homes, >= 75 years and >= 5 drugs. Home visits were performed to all, including prescription reviews and calculation of medication appropriateness index. The patients were divided into three groups depending on index score and followed for 12 months. The validated and recognized EQ-5D and EQ VAS instruments were used to assess quality of life. RESULTS: A lower medication quality was associated with a lower quality of life. EQ-5D index was statistically significantly different (declining for each group) among the groups (p = 0.001 at study start, p = 0.001 at 6 months and p = 0.013 at 12 months) as was EQ VAS (p = 0.026 at study start, p = 0.003 at 6 months and p = 0.007 at 12 months). CONCLUSIONS: This study has shown the validity of the basic principle in prescribing: the more appropriate medication the better quality of life. Since drug quality is related to the patients' quality of life, there is immense reason to continuously evaluate every prescription and treatment. The evaluation and if possible deprescribing should be done as a process where both the patient and physician are involved. PMID- 22054207 TI - Natalizumab discontinuation: an increasingly tricky proposition. PMID- 22054208 TI - Atypia predicting prognosis for intracranial extraventricular neurocytomas. AB - OBJECT: The literature, at present, provides limited information about extraventricular neurocytomas (EVNs) and is almost exclusively composed of case reports or small case series. Treatment for EVNs has largely been guided by results from central neurocytoma outcome studies. The authors present an analysis of all reported intracranial EVN cases to establish if tumor histopathological features can substratify EVN into groups with differing prognosis and help guide treatment decisions. METHODS: The authors identified studies reporting histology, treatment modality, and outcomes for patients with intracranial EVN. The rates of recurrence and survival for patients were compared using Kaplan-Meier analysis. Atypical tumors, defined by MIB-1 labeling index exceeding 3% or atypical histological features, were compared with typical tumors, and patients 50 years of age or older were compared with those younger than 50 years of age. RESULTS: Eighty-five patients met the inclusion criteria, and 27% of them had an atypical histology. Typical EVNs had a better prognosis than atypical EVNs after primary treatment, with a 5-year recurrence rate of 36% compared with 68% (p < 0.001), and a 5-year mortality rate of 4% compared with 44%, respectively (p < 0.001). Age younger 50 years was associated with a better prognosis than age equal to or greater than 50 years, with a 5-year recurrence rate of 33% and 74%, respectively (p < 0.001), and a 5-year mortality rate of 4% and 52%, respectively (p < 0.001). Multivariate analysis demonstrated that atypical EVNs carried significantly increased risk for recurrence (hazard ratio [HR] 4.91, p < 0.001) and death (HR 22.91, p < 0.01). Gross-total resection was superior to subtotal resection (STR) alone in tumor control rates for typical EVNs (95% and 68%, p < 0.05), and there was a trend for adjuvant external-beam radiotherapy to benefit STR. There was suggestion of similar trends in patients with atypical EVNs. CONCLUSIONS: There are at least 2 distinct histological subtypes of EVN, with different prognostic significances. Atypia or MIB-1 labeling index greater than 3% is a significant predictor of poor prognosis for EVNs. Complete resection or more aggressive attempts at providing adjuvant therapy following STR appear to improve the prognosis for patients with EVNs. Although the authors' results are informative, there are limitations to their analysis. Given the relatively modest total number of cases reported, as well as the nature of the disaggregated analysis, the authors were not able to use formal meta-analytical methods to limit the impact of between center heterogeneity. Additionally, they were not able to control for individual differences in data analysis and presentation across the different studies included in their analysis. PMID- 22054209 TI - Clinical data simplified. PMID- 22054210 TI - Impact test comparisons of 20th and 21st century American football helmets. AB - OBJECT: Concussion is the signature American football injury of the 21st century. Modern varsity helmets, as compared with vintage leather helmets, or "leatherheads," are widely believed to universally improve protection by reducing head impact doses and head injury risk for the 3 million young football players in the US. The object of this study was to compare the head impact doses and injury risks with 11 widely used 21st century varsity helmets and 2 early 20th century leatherheads and to hypothesize what the results might mean for children wearing similar varsity helmets. METHODS: In an injury biomechanics laboratory, the authors conducted front, oblique front, lateral, oblique rear, and rear head impact tests at 5.0 m/second using helmeted headforms, inducing near- and subconcussive head impact doses on par with approximately the 95th percentile of on-field collision severity. They also calculated impact dose injury risk parameters common to laboratory and on-field traumatic neuromechanics: linear acceleration, angular acceleration, angular velocity, Gadd Severity Index, diffuse axonal injury, acute subdural hematoma, and brain contusion. RESULTS: In many instances the head impact doses and head injury risks while wearing vintage leatherheads were comparable to or better than those while wearing several widely used 21st century varsity helmets. CONCLUSIONS: The authors do not advocate reverting to leather headgear, but they do strongly recommend, especially for young players, instituting helmet safety designs and testing standards, which encourage the minimization of linear and angular impact doses and injury risks in near- and subconcussive head impacts. PMID- 22054211 TI - The Barrow Ruptured Aneurysm Trial. PMID- 22054212 TI - Cerebral aneurysms with intrasellar extension: a systematic review of clinical, anatomical, and treatment characteristics. AB - OBJECT: Intrasellar aneurysms are rare lesions that often mimic pituitary tumors, potentially resulting in catastrophic outcomes if they are not appropriately recognized. The authors aimed to characterize the clinical and anatomical details of this poorly defined entity in the modern era of neuroimaging and open/endovascular neurosurgery. METHODS: A PubMed literature review was conducted to identify all studies reporting noniatrogenic aneurysms with intrasellar extension, as confirmed by CT or MR imaging and angiography. Clinical, anatomical, and treatment characteristics were analyzed. RESULTS: Thirty-one studies reporting 40 cases of intrasellar aneurysms were identified. Six patients (15%) presented with aneurysmal rupture. Patients with unruptured aneurysms presented with the following signs and symptoms: headache (61%), visual field cuts/decreased visual acuity (61%), endocrinopathy (57%), symptomatic hyponatremia (21%), and cranial nerve paresis (other than optic nerve) (18%). The most common endocrine abnormalities were hyperprolactinemia and hypogonadism. Eight aneurysms (20%) were diagnosed in conjunction with a pituitary adenoma. Aneurysms could be categorized into 2 primary anatomical groups as follows: 1) cavernous/clinoid segment internal carotid artery (ICA) (infradiaphragmatic) aneurysms with medial extension into the sella; and 2) suprasellar (supradiaphragmatic) aneurysms originating from the ophthalmic segment of the ICA or from the anterior communicating artery, with inferomedial extension into the sella. The mean diameters of infradiaphragmatic and supradiaphragmatic aneurysms were 14.5 and 21.8 mm, respectively. Infradiaphragmatic aneurysms were much more likely to present with endocrinopathy, whereas supradiaphragmatic ones presented more commonly with visual disturbances. Aneurysms with infradiaphragmatic growth were generally treated using either endovascular techniques or surgical trapping and bypass, while supradiaphragmatic aneurysms were more often treated by surgical clipping. CONCLUSIONS: Aneurysms with intrasellar extension typically present due to mass effect on surrounding structures, and they can be classified as infradiaphragmatic cavernous or clinoid segment ICA aneurysms, or supradiaphragmatic ophthalmic ICA or anterior communicating artery aneurysms. Varying approaches exist for treating these complex aneurysms, and intervention strategies depend substantially on the anatomical subtype. PMID- 22054213 TI - The Barrow Ruptured Aneurysm Trial. AB - OBJECT: The purpose of this ongoing study is to compare the safety and efficacy of microsurgical clipping and endovascular coil embolization for the treatment of acutely ruptured cerebral aneurysms and to determine if one treatment is superior to the other by examining clinical and angiographic outcomes. The authors examined the null hypothesis that no difference exists between the 2 treatment modalities in the setting of subarachnoid hemorrhage (SAH). The current report is limited to the clinical results at 1 year after treatment. METHODS: The authors screened 725 patients with SAH, resulting in 500 eligible patients who were enrolled prospectively in the study after giving their informed consent. Patients were assigned in an alternating fashion to surgical aneurysm clipping or endovascular coil therapy. Intake evaluations and outcome measurements were collected by nurse practitioners independent of the treating surgeons. Ultimately, 238 patients were assigned to aneurysm clipping and 233 to coil embolization. The 2 treatment groups were well matched. There were no anatomical exclusions. Crossing over was allowed, but primary outcome analysis was based on the initial treatment modality assignment. Posttreatment care was standardized for both groups. Patient outcomes at 1 year were independently assessed using the modified Rankin Scale (mRS). A poor outcome was defined as an mRS score > 2 at 1 year. The primary outcome was based on the assigned group; that is, by intent to treat. RESULTS: One year after treatment, 403 patients were available for evaluation. Of these, 358 patients had actually undergone treatment. The remainder either died before treatment or had no identifiable source of SAH. A poor outcome (mRS score > 2) was observed in 33.7% of the patients assigned to aneurysm clipping and in 23.2% of the patients assigned to coil embolization (OR 1.68, 95% CI 1.08-2.61; p = 0.02). Of treated patients assigned to the coil group, 124 (62.3%) of the 199 who were eligible for any treatment actually received endovascular coil embolization. Patients who crossed over from coil to clip treatment fared worse than patients assigned to coil embolization, but no worse than patients assigned to clip occlusion. No patient treated by coil embolization suffered a recurrent hemorrhage. CONCLUSIONS: One year after treatment, a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes than clip occlusion. Although most aneurysms assigned to the coil treatment group were treated by coil embolization, a substantial number crossed over to surgical clipping. Although a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes at 1 year, it remains important that high-quality surgical clipping be available as an alternative treatment modality. PMID- 22054215 TI - Reactions of late lanthanide metal atoms and methanol in solid argon: a matrix isolation infrared spectroscopic and theoretical study. AB - The reactions of laser-ablated late lanthanide atoms and methanol were studied using matrix isolation infrared spectroscopy and electronic structure calculations at the density functional theory level. Both terbium and lutetium atoms react with methanol spontaneously to form the CH(3)OTbH and CH(3)OLuH insertion products, which react further with another methanol molecule to give the Tb(OCH(3))(2) and Lu(OCH(3))(2) products as found previously for uranium. The reactions of Dy through Yb and methanol first produce Ln(CH(3)OH) complexes during sample annealing, which isomerize to the CH(3)OLnH insertion products on visible irradiation. The Ln-H stretching frequencies of the CH(3)OLnH molecules exhibit a unique trend from Tb to Lu, which is also reproduced by theoretical calculations at the B3LYP level of theory. Although the CH(3)LnOH molecules are predicted to be more stable than the O-H bond insertion products, formation of the C-O bond insertion isomers is kinetically prohibited as revealed by calculated potential energy surfaces. PMID- 22054214 TI - Progesterone-induced changes in the phosphoryl potential during the meiotic divisions in amphibian oocytes: role of Na/K-ATPase. AB - BACKGROUND: Progesterone triggers resumption of the first meiotic division in the Rana pipiens oocyte by binding to the N-terminal external loop of the catalytic subunit of Na/K-ATPase, releasing a cascade of lipid second messengers. This is followed by internalization of specific membrane proteins, plasma membrane depolarization and nuclear membrane breakdown, culminating in arrest at second metaphase. RESULTS: Progesterone initiates an increase in phosphoryl potential during the first meiotic division, resulting in the accumulation of high energy protein phosphate by second metaphase arrest. 31P-NMR, with saturation transfer, demonstrates that the phosphocreatine level rises ~2 fold and that the "pseudo" first order rate constant for the creatine kinase reaction falls to ~20% of the control by the onset of nuclear membrane breakdown. 32PO4 pulse-labeling reveals a net increase in phosphorylation of yolk protein phosvitin during this period. The increased yolk protein phosphorylation coincides with internalization of membrane Na/K-ATPase and membrane depolarizatio CONCLUSIONS: These results indicate that progesterone binding to the catalytic subunit of the Na-pump diverts ATP from cation regulation at the plasma membrane to storage of high energy phosphate in yolk protein. Phosvitin serves as a major energy source during fertilization and early cleavage stages and is also a storage site for cations (e.g. Na+, K+, Ca2+, Fe2+/3+) essential for embryonic development. PMID- 22054216 TI - Multiple psychosomatic symptoms can indicate child physical abuse - results from a study of Swedish schoolchildren. AB - AIM: To examine whether children with self-reported experiences of either physical abuse alone or combined with intimate partner violence report more psychosomatic symptoms than other children and to explore whether these possible associations are enhanced by school-related factors, chronic condition and demographic factors. METHODS: A national cross-sectional study of 2771 pupils in grades 4, 6 and 9 from 44 schools in Sweden was carried out in 2006 (91% response rate). Data were analysed with univariate tests (chi-square), multiple logistic regression analyses and stratified logistic regression analyses, expressed as crude odds ratio (OR) and adjusted odds ratio (AOR) with 95% confidence intervals. RESULTS: There was a strong association between reported physical abuse and multiple (three or more) psychosomatic symptoms among schoolchildren (AOR 2.12). Chronic condition was the only determinant that had an obvious enhancing effect on the association between physical abuse and psychosomatic symptoms in childhood. CONCLUSION: This study shows that multiple psychosomatic symptoms are associated with child physical abuse. Health professionals therefore need to pay special attention to schoolchildren who complain about the co occurrence of psychosomatic symptoms and pattern of symptoms, which could not be easily explained by other causes. PMID- 22054217 TI - Pyosalpinx as a sequela of labial fusion in a post-menopausal woman: a case report. AB - INTRODUCTION: Complete labia fusion is a rare clinical entity in post-menopausal women. The most common complications of this presentation are infections of the urinary tract and retention of urine in the vagina. We present the case of a post menopausal woman with adnexal mass and abdominal pain due to fusion of the labia majora. To the best of our knowledge this is the first report in the literature of this complication. CASE PRESENTATION: A 78-year-old Caucasian woman was admitted to our hospital due to abdominal pain and urination difficulty, along with fever and leucocytosis. On examination the labial majora were fused. Computed tomography of the abdomen revealed a cystic formation in the anatomical area of the right adnexa. Our patient had developed a pyosalpinx as a Sequela of labial fusion. At laparoscopy the right pyosalpinx was identified and resected, whereas the labia majora were reconstructed via dissection and separation. CONCLUSIONS: Labial fusion is a rare clinical entity in post-menopausal women and can have serious and unexpected complications. Though this presentation is rare, a clinical examination must be performed in detail in order to gain valuable information for an accurate diagnosis. Post-operational instruction must be given to patients in order to prevent the re-occurrence of the fusion and its complications. PMID- 22054218 TI - The challenge to sustainable development in China revealed by "death villages". PMID- 22054219 TI - EMSA and single-molecule force spectroscopy study of interactions between Bacillus subtilis single-stranded DNA-binding protein and single-stranded DNA. AB - In this article, interactions between Bacillus subtilis single-stranded DNA binding proteins (BsSSB) and single-stranded DNA (ssDNA) were systematically studied. The effect of different molar ratios between BsSSB and ssDNA on their binding modes was first investigated by electrophoretic mobility shift assays (EMSAs). It is found that a high molar ratio of BsSSB to ssDNA can produce BsSSB ssDNA complexes formed in the mode of two proteins binding one 65-nt (nucleotide) ssDNA whereas a low molar ratio facilitates the formation of BsSSB-ssDNA complexes in the mode of one protein binding one 65-nt ssDNA. Furthermore, two binding modes are in dynamic equilibrium. The unbinding force of BsSSB-ssDNA complexes was measured quantitatively in solutions with different salt concentrations by using AFM-based single-molecule force spectroscopy (SMFS). Our results show that the unbinding force is about 10 pN higher at high salt concentration (0.5 M NaCl) than at low salt concentration (0.1 M NaCl) and the lifetime of BsSSB-ssDNA complexes at high salt concentration is twice as long as that at low salt concentration. These results indicate that more tightly packed BsSSB-ssDNA complexes can form at high salt (0.5 M NaCl) concentration. In addition, the results of EMSA show that ssDNA, which is bound to BsSSB, can dissociate from BsSSB in the presence of the cDNA strand, indicating the dynamic nature of BsSSB-ssDNA interactions. PMID- 22054220 TI - Using geographical information systems mapping to identify areas presenting high risk for traumatic brain injury. AB - BACKGROUND: The aim of this study is to show how geographical information systems (GIS) can be used to track and compare hospitalization rates for traumatic brain injury (TBI) over time and across a large geographical area using population based data. RESULTS & DISCUSSION: Data on TBI hospitalizations, and geographic and demographic variables, came from the Ontario Trauma Registry Minimum Data Set for the fiscal years 1993-1994 and 2001-2002. Various visualization techniques, exploratory data analysis and spatial analysis were employed to map and analyze these data. Both the raw and standardized rates by age/gender of the geographical unit were studied. Data analyses revealed persistent high rates of hospitalization for TBI resulting from any injury mechanism between two time periods in specific geographic locations. CONCLUSIONS: This study shows how geographic information systems can be successfully used to investigate hospitalizaton rates for traumatic brain injury using a range of tools and techniques; findings can be used for local planning of both injury prevention and post discharge services, including rehabilitation. PMID- 22054221 TI - Spatially resolved protein hydrogen exchange measured by matrix-assisted laser desorption ionization in-source decay. AB - Mass spectrometry has become a powerful tool for measuring protein hydrogen exchange and thereby reveal the structural dynamics of proteins in solution. Here we describe the successful application of a matrix-assisted laser desorption ionization (MALDI) mass spectrometry approach based on in-source decay (ISD) to measure spatially resolved amide backbone hydrogen exchange. By irradiating deuterated protein molecules in a crystalline matrix with a high laser fluence, they undergo prompt fragmentation. Spatially resolved deuteration levels are readily obtained by mass analysis of consecutive fragment ions. MALDI ISD analysis of deuterated cytochrome c yielded an extensive series of c-fragment ions which originate from cleavage of nearly all N-C(alpha) bonds (Cys17 to Glu104) allowing for a detailed analysis of the deuterium content of the backbone amides. While hydrogen scrambling can be major concern when using mass spectrometric fragmentation to obtain detailed information on protein hydrogen exchange, we show that the level of hydrogen scrambling in our MALDI ISD measurements is negligible and that the known dynamic behavior of cytochrome c in solution is accurately reflected in the deuterium contents of the fragment ions. The developed method combines several attractive features from a practical point of view as it is simple to perform and it readily provides a detailed mapping of the dynamic structure of a protein in solution. PMID- 22054222 TI - Child burn injury in Dar es Salaam, Tanzania: results from a community survey. AB - The objective of this study was to identify the incidence of burn injuries among children in a sub-Saharan urban area and describe contributing factors in the home environment. A cross-sectional household survey was conducted in Dar es Salaam, Tanzania between 8 and 22 July 2009. Demographic characteristics of participants were reported using descriptive statistics. Bivariate analyses using Pearson's chi-square tests for categorical variables were used to explore possible associations. Burns represented 16.3% of reported injuries. The one month incidence was calculated to be 1.73%. The most common contributor to burn injury was open flame 36.9%, followed by hot liquids 33.8%. Most burns occurred in urban areas with 88% occurring in the home. A significant association with burn injury was found in the 0-4 age category. There exists a continued need for research examining the mechanisms of safety provision in the home in low resource settings, especially concerning burn injury. PMID- 22054223 TI - Rationale and design of a prospective study: Cervical Dystonia Patient Registry for Observation of OnaBotulinumtoxinA Efficacy (CD PROBE). AB - BACKGROUND: A registry of patients with cervical dystonia (Cervical Dystonia Patient Registry for Observation of onaBotulinumtoxinA Efficacy [CD PROBE]) was initiated to capture data regarding physician practices and patient outcomes with onabotulinumtoxinA (BOTOX(r), Allergan, Inc., Irvine, CA, USA). Methods and baseline demographics from an interim analysis are provided. METHODS/DESIGN: This is a prospective, multicenter, clinical registry in the United States enrolling subjects with cervical dystonia (CD) who are toxin naive and/or new to the physicians' practices, or who had been in a clinical trial but received their last injection >= 16 weeks prior to enrollment. Subjects are followed over 3 injection cycles of onabotulinumtoxinA, with assessments at time of injection and 4-6 weeks later. Information on physician's practice, patient demographics, CD disease history, duration of treatment intervals and neurotoxin dose, dilution, use of electromyography, and muscles injected are collected. Outcomes are assessed by physicians and subjects using various questionnaires. DISCUSSION: This ongoing registry includes 609 subjects with the following baseline data: 75.9% female, 93.6% Caucasian, mean age 57.6 +/- 14.3, age at symptom onset 48.3 +/- 16.2, and time to diagnosis 5.4 +/- 8.6 years, with an additional 1.0 +/- 3.5 years before treatment. Of those employed at the time of diagnosis, 36.6% stopped working as a result of CD. CD PROBE, the largest clinical registry of CD treatment, will provide useful data on current treatment practices with onabotulinumtoxinA, potentially leading to refinements for optimization of outcomes. TRIAL REGISTRATION: NCT00836017. PMID- 22054224 TI - A whole-person model of care for persistent pain: from conceptual framework to practical application. AB - SETTING: The study was set in an Australian tertiary public hospital multidisciplinary pain center. OBJECTIVES: The objectives of the study were to describe the conceptual shift undertaken by a multidisciplinary team in moving from a traditional approach to an emerging paradigm in pain medicine and to describe the practical application of a whole-person model of care and report outcomes over the period 2003-2010. DESIGN: The study design was descriptive, including a brief review of current evidence base, consideration of models of service delivery, and analysis of the impact of applying a new, whole-person model of care for persistent pain. INTERVENTION: Since 2004, a series of changes led to significant health system redesign. The process involved development of a broader, whole-person understanding of the individual with pain and a more integrated approach to service delivery across the spectrum from community to tertiary care. RESULTS: Broad trends in the period 2003-2010 included a modest reduction in referral rate, marked reduction in waiting times, more efficient staff utilization, inversion of the ratio of new assessments to review appointments, increased telephone contact with primary care, increased use of personalized pain management plans, reduced procedural interventions and increased attendance at and clinically significant gains from shorter and more flexible group programs. CONCLUSIONS: Changes to conceptual framework inevitably influence the practicalities of service delivery. The application of a whole-person model for persistent pain brought improved engagement with the individual in pain and more efficient delivery of care at a systems level. PMID- 22054225 TI - Genetic parameters of total milk yield and factors describing the shape of lactation curve in dairy buffaloes. AB - The objective of this study was to apply factor analysis to describe lactation curves in dairy buffaloes in order to estimate the phenotypic and genetic association between common latent factors and cumulative milk yield. A total of 31 257 monthly test-day milk yield records from buffaloes belonging to herds located in the state of Sao Paulo were used to estimate two common latent factors, which were then analysed in a multi-trait animal model for estimating genetic parameters. Estimates of (co)variance components for the two common latent factors and cumulated 270-d milk yield were obtained by Bayesian inference using a multiple trait animal model. Contemporary group, number of milkings per day (two levels) and age of buffalo cow at calving (linear and quadratic) as covariate were included in the model as fixed effects. The additive genetic, permanent environmental and residual effects were included as random effects. The first common latent factor (F1) was associated with persistency of lactation and the second common latent factor (F2) with the level of production in early lactation. Heritability estimates for F1 and F2 were 0.12 and 0.07, respectively. Genetic correlation estimates between F1 and F2 with cumulative milk yield were positive and moderate (0.63 and 0.52). Multivariate statistics employing factor analysis allowed the extraction of two variables (latent factors) that described the shape of the lactation curve. It is expected that the response to selection to increase lactation persistency is higher than the response obtained from selecting animals to increase lactation peak. Selection for higher total milk yield would result in a favourable correlated response to increase the level of production in early lactation and the lactation persistency. PMID- 22054226 TI - Assembly of digitoxin by gold(I)-catalyzed glycosidation of glycosyl o alkynylbenzoates. AB - Digitoxin, a clinically important cardiac trisaccharide, was assembled efficiently from digitoxigenin and 3,4-di-O-tert-butyldiphenylsilyl-d-digitoxosyl o-cyclopropylethynylbenzoate in 9 steps and 52% overall yield via alternate glycosylation and protecting group manipulation. The present synthesis showcases the advantage of the gold(I)-catalyzed glycosylation protocol in the synthesis of glycoconjugates containing acid-labile 2-deoxysugar linkages. PMID- 22054227 TI - The European Medicines Agency discovers the geriatric patient. PMID- 22054228 TI - Optimal management of cancer treatment-induced bone loss: considerations for elderly patients. AB - Hormone manipulation, commonly used in breast and prostate cancer, can result in significant bone loss. In multiple myeloma (MM), corticosteroids play an important role in therapy but increase the risk of fracture over that expected for any given bone mineral density. These adverse effects on the skeletal system are particularly relevant in the elderly population, in whom osteoporosis can significantly affect not only quality of life but also survival. The associated health and social care costs are becoming increasingly important. Screening with dual energy x-ray absorptiometry (DXA) scans and lifestyle advice on smoking, alcohol and dietary intake are essential parts of the management of patients with cancer treatment-induced bone loss. The value of exercise also cannot be underestimated. A careful drug review should be carried out to eliminate agents that may potentially exacerbate bone toxicity. Therapies to address bone toxicities include bisphosphonates, which have been shown to play an increasingly important role in preventing declines in bone health. The issues of compliance when oral agents are used should not be underestimated. Renal toxicity and osteonecrosis of the jaw are relevant toxicities, especially in the elderly. Cardiac toxicity has not been proven, but there is evidence to suggest that the suppression of bone turnover seen with some, although not all, bisphosphonates is not reversed following cessation of treatment. The implications of this finding need to be borne in mind when treating elderly patients. The possibility of atypical fractures in patients taking bisphosphonates also needs to be given consideration, although this remains a rare complication. Recently, the receptor activator of nuclear factor-kappaB ligand (RANKL) ligand antibody denosumab has been shown to be of value in fracture prevention, and its subcutaneous route of administration offers a potential advantage. Oncologists should also remember that tamoxifen, which has little effect on bone integrity, remains a useful drug for breast cancer patients. A multidisciplinary approach involving the hospital specialist, general practitioner, nurse and, most importantly, the patient, family and carers should ensure that the maximal benefit is received from the anti-cancer treatment, with minimal cost to the patient. As cancer cure rates increase, late toxicity is increasingly relevant and challenging. The skeletal system warrants more research to maximize the care of all our patients, especially the elderly, who may be most at risk. PMID- 22054229 TI - Optimal pharmacotherapeutic strategies for elderly patients with advanced non small cell lung cancer. AB - Increases in both life expectancy and cancer incidence with age result in a significant rise in lung cancer rates among elderly patients, with a median age at diagnosis of between 63 and 70 years. However, elderly patients are under represented in clinical trials and generally receive suboptimal treatment, mainly because of fears about increased toxicity of chemotherapy. Indeed, physiological modification of renal and haematopoietic functions with age together with co morbidity and associated polypharmacy may alter the metabolism of chemotherapy drugs, resulting in greater toxicity. Moreover, performance status (PS), the main prognostic factor in younger patients, does not correlate well with geriatric indexes such as activities of daily living, cognition and physical performance, and comprehensive geriatric assessment is important in elderly patients. Until 2010, based on the small number of clinical trials designed for elderly patients, monotherapy was the recommended treatment for those with advanced non-small cell lung cancer (NSCLC), whereas for fit younger patients, a platinum-based doublet was and continues to be the recommended first-line therapy. However, at the plenary session of the 2010 Annual Meeting of the American Society of Clinical Oncology, results were presented from a randomized controlled trial conducted by the French Intergroup of Thoracic Oncology that demonstrated that in PS 0-2 patients aged>=70 years with advanced NSCLC, monthly carboplatin with weekly paclitaxel resulted in significantly longer survival than single-agent therapy (vinorelbine or gemcitabine). It should be noted that even in a priori unfavourable prognostic subgroups (patients with a PS score of 2, those aged>80 years or those with an activities of daily living scale score of <6), doublet therapy was associated with a survival advantage over monotherapy. Thus, the new paradigm of treatment of elderly patients with advanced NSCLC and a PS score of 0 2 should now be monthly carboplatin with weekly paclitaxel. While there have been no trials of second-line therapy for NSCLC specifically in elderly patients, exploratory subgroup analyses indicate that docetaxel, pemetrexed and erlotinib may provide outcomes in elderly patients similar to those reported in younger patients. However, specific second-line therapy trials in elderly patients are required as the elderly patients in trials conducted to date were probably highly selected to fit the inclusion criteria. There is no more room for nihilism in the treatment of elderly patients with advanced NSCLC. Such patients should be evaluated carefully by geriatric indexes and, if they have a PS score of 0-2, may be treated with platinum-based (mostly carboplatin) doublet therapy in the same manner as their younger counterparts. The optimal second line treatment remains to be determined. PMID- 22054230 TI - Serotonin-norepinephrine reuptake inhibitor antidepressants and the risk of falls in older people: case-control and case-series analysis of a large UK primary care database. AB - BACKGROUND: Antidepressant medications have long been implicated as a cause of falls in older people, but there are few data on the risk of falls associated with exposure to serotonin-norepinephrine (noradrenaline) reuptake inhibitors (SNRIs). OBJECTIVE: The aim of this study was to determine the role of SNRIs in older people with a recorded fall in primary care using a case-control approach and a self-controlled case-series analysis of data from The Health Improvement Network (THIN) UK primary care database. METHODS: Cases were 9862 individuals aged >60 years with a first fall recorded between 2003 and 2006. Up to six controls per case were matched by age, sex and primary care practice. For the case-series analysis, we extended our case set to those with a first fall recorded between 2001 and 2008. We estimated odds ratios (ORs) for 'ever', 'current', 'recent', 'previous' or 'never' prescribed SNRIs (and for the other main classes of antidepressants, for comparison) in cases compared with matched controls, using conditional logistic regression. We also examined the effect of the time interval from first prescription to first fall. In the case-series analysis, we compared the rate of occurrence of first falls during episodes of exposure to SNRIs with unexposed periods in our case group. RESULTS: There was an increased risk of current prescribing of SNRIs (adjusted OR 1.79; 95% CI 1.42, 2.25) in first fall cases compared with controls. This was similar in magnitude to that seen with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The increase in risk was apparent within the first 28 days after first prescription. The effects were also apparent in the self controlled case-series analysis, although the magnitudes of effect were slightly smaller; the incidence risk ratio for the period 1-28 days after initiation of treatment compared with unexposed periods was 1.49 (95% CI 1.15, 1.93). CONCLUSIONS: Treatment with SNRIs in older people may be associated with an increased risk of falling. The falls risk profile of SNRIs appears to be similar to that of SSRIs and TCAs. PMID- 22054231 TI - Pharmacokinetics and pharmacodynamics of meropenem in elderly chinese with lower respiratory tract infections: population pharmacokinetics analysis using nonlinear mixed-effects modelling and clinical pharmacodynamics study. AB - BACKGROUND: Meropenem is a broad-spectrum antibacterial that is usually used in the treatment of serious lower respiratory tract infections (LRTIs). However, there is a lack of published studies exploring the correlation between the population pharmacokinetics of meropenem, the clinical pharmacodynamics of the drug and the response to the drug in Chinese patients with LRTIs, especially in the elderly. OBJECTIVE: The aim of this study was to develop a pharmacokinetic model of meropenem using patient data and use this to explore the clinical pharmacodynamics of meropenem in the treatment of LRTIs in elderly Chinese patients. METHODS: We measured serum meropenem concentrations in patients who had received meropenem 0.5 or 1.0 g infused over 0.5 hours every 8 or 12 hours, respectively. The pharmacokinetic analysis of meropenem was performed using nonlinear mixed-effects modelling (NONMEM(r)) software. The minimum inhibitory concentration (MIC) of meropenem against Gram-negative bacilli was tested by the E-test method. The pharmacodynamic parameters of percentage of time above MIC (%T>MIC), the ratio of the drug area under the serum concentration-time curve to MIC (AUC/MIC), the ratio of the maximum serum concentration of the drug to MIC (Cmax/MIC) and the ratio of the minimum serum concentration of the drug to MIC (Cmin/MIC) were analysed for their association with clinical and bacteriological outcomes. RESULTS: A total of 284 serum meropenem concentration measurements were obtained from 75 patients (aged 63-95 years). A two-compartment model fitted the concentration data best. The covariates creatinine clearance (CLCR) and Acute Physiology and Chronic Health Evaluation (APACHE) II score had the most significant effects on meropenem pharmacokinetics. Forty-five patients were enrolled in the pharmacodynamic study, including 25 clinical responders and 21 patients with bacteriological eradication. All of the 45 patients had Gram negative bacilli isolated from tracheal aspirate or sputum. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values for the 25 clinical responders were significantly higher than those for the nonresponders (all p<0.05). However, logistic regression analysis showed that only %T>MIC independently influenced clinical outcome (p=0.001, odds ratio [OR]=1.065). The cut-off value for predicting clinical success using %T>MIC was 76%; the sensitivity and specificity of %T>MIC for predicting a successful response were 84% and 85%, respectively. The %T>MIC, AUC/MIC, Cmax/MIC and Cmin/MIC values, and the serum level of albumin, for the 21 patients with bacteriological eradication were significantly higher than those for patients with bacteriological treatment failure (all p<0.05). Logistic regression analysis showed that %T>MIC (p=0.008, OR=1.047) and serum level of albumin (p=0.033, OR=1.434) independently influenced bacteriological eradication. CONCLUSIONS: To our knowledge, this is the first study to investigate the population pharmacokinetics and clinical pharmacodynamics of meropenem in elderly Chinese. CLCR and APACHE II score have significant influences on meropenem pharmacokinetics. In LRTI patients, the cut-off value of 76% for %T>MIC can be applied to optimize their meropenem dose regimen to achieve clinical success. PMID- 22054232 TI - Sedative load among community-dwelling people aged 75 years and older: a population-based study. AB - BACKGROUND: Drugs with sedative properties are among the most widely used drugs in community-dwelling older people. Use of sedative drugs has been associated with falls and fractures, cognitive and memory impairment and impaired physical function among older people. The sedative load model has been developed to quantify the cumulative effect of taking multiple drugs with sedative properties. OBJECTIVE: The objective of the study was to investigate factors associated with sedative load among community-dwelling older people, using data collected as part of the Finnish Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) study. METHODS: The GeMS study was a randomized, comparative study that evaluated a model for geriatric assessment, care and rehabilitation using a study sample of 1000 persons aged>=75 years who were living in Kuopio, Finland. Of these, 700 people consented to participate and were community-dwelling. Demographic, diagnostic and drug use data (both regular and when-required drugs) were elicited during nurse interviews. For the current analysis, sedative load was computed using a previously published model, in which drugs taken on a regular and when-required basis were classified into one of four groups according to their sedative potential. Group 1 included primary sedatives (sedative rating 2) and group 2 included drugs with sedation as a prominent side effect (sedative rating 1). Each participant's sedative load was calculated by summing the sedative ratings of group 1 and 2 drugs. Logistic regression models were used to investigate factors associated with sedative load. RESULTS: Twenty-nine percent of participants (n=205) had a sedative load of >=1 (i.e. used one or more drugs with sedative properties), and 22% (n=158) had a sedative load of >=2 (i.e. used either one primary sedative or two drugs with sedation as a prominent adverse effect or preparations with a sedating component) when considering regularly used drugs. A sedative load of >=2 that related to regularly used drugs was associated with female sex (odds ratio [OR] 1.65; 95% CI 1.02, 2.67), poor self-perceived health (OR 2.06; 95% CI 1.25, 3.38), impaired instrumental activities of daily living [IADL] (OR 1.89; 95% CI 1.18, 3.01) and often feeling lonely (OR 4.72; 95% CI 2.15, 10.40). The same factors remained significantly associated with a sedative load of >=2 after drugs used on a when-required basis were included in the analyses. CONCLUSIONS: The advantages of the sedative load model were that it included drugs with sedative properties prescribed for somatic diseases, described cumulative exposure to drugs that exert sedative effects through multiple mechanisms in the CNS, and incorporated a sedative rating for each drug. In an older population, female sex, impaired IADL, poor self-perceived health, and loneliness were associated with higher sedative load. Clinicians should remain cognizant of these factors when reviewing drug regimens and targeting interventions to optimize sedative use. PMID- 22054233 TI - Spotlight on rivastigmine transdermal patch: in dementia of the Alzheimer's type. AB - Rivastigmine, a cholinesterase inhibitor, is available as a transdermal patch (Exelon(r) patch, Rivastach(r) patch, Prometax(r) patch) for the treatment of mild to moderate Alzheimer's disease. Rivastigmine transdermal patch was effective, in terms of improving cognitive and global function, and generally well tolerated in patients with mild to moderate dementia of the Alzheimer's type in a large, well designed trial. Most adverse events associated with rivastigmine patch were mild to moderate in severity, with the patch generally better tolerated than oral rivastigmine, especially in terms of cholinergic gastrointestinal adverse events. The patch also had good skin adhesion and a favourable skin tolerability profile in this study, with most application-site reactions being mild in severity. Additionally, in a safety and tolerability study, rivastigmine patch, regardless of concomitant memantine therapy, was generally well tolerated in patients switching from oral donepezil therapy. Thus, current evidence suggests that rivastigmine transdermal patch is an effective treatment option for patients with Alzheimer's disease, with the potential for improving compliance and providing sustained clinical benefit because of its ease of use and generally favourable tolerability profile. PMID- 22054234 TI - Safety aspects of deep sedation during catheter ablation of atrial fibrillation. AB - BACKGROUND: The combination of intravenous propofol and midazolam is frequently used to provide unconscious sedation during catheter ablation of atrial fibrillation (AF), but only a very few reports are available on the influence of prolonged propofol infusion on arterial blood gas, blood pressure, and anesthesia associated complications during ablation of AF. The purpose of this study was to assess tolerance and safety of unconscious sedation with intravenous propofol and midazolam during catheter ablation of AF. METHODS: A total of 316 consecutive patients (age 59 +/- 10 years, 68% men) presenting to our center for catheter ablation of symptomatic AF were enrolled prospectively. A total number of 424 procedures were performed under unconscious sedation with propofol and midazolam. SaO(2), electrocardiogram, arterial blood pressure, and arterial blood gases were monitored throughout the procedure. RESULTS: Mean procedure duration was 235 +/- 48 minutes. Patients received 1.125 +/- 684 mg propofol, 9.5 +/- 3 midazolam, and 1.963 +/- 813 mL NaCl infusion. Complications during the procedure were identified in eight patients (2.5%, one * coronary air embolization, one * myocardial infarction, four * pericardial effusion, two * pericardial tamponade). All eight patients were symptomatic (distress, report of pain); none of the complications was attributable to unconscious sedation itself. CONCLUSION: Unconscious sedation with propofol and midazolam in AF ablation procedures lasting 3-5 hours did not result in severe changes of vital parameters or serum electrolytes. Anesthesia-associated problems were not observed. Propofol and midazolam can be safely used during catheter ablation of AF. PMID- 22054235 TI - New insights into the structure of the reaction centre from Blastochloris viridis: evolution in the laboratory. AB - Newly determined crystal structures of the photosynthetic RC (reaction centre) from two substrains of the non-sulfur purple bacterium Blastochloris viridis strain DSM 133, together with analysis of their gene sequences, has revealed intraspecies evolutionary changes over a period of 14 years. Over 100 point mutations were identified between these two substrains in the four genes encoding the protein subunits of the RC, of which approximately one-fifth resulted in a total of 16 amino acid changes. The most interesting difference was in the M subunit where the change from a leucine residue to glycine in the carotenoid binding pocket allowed NS5 (1,2-dihydroneurosporene) to adopt a more sterically favoured conformation, similar to the carotenoid conformation found in other related RCs. The results of the present study, together with a high rate of mutations in laboratory bacterial cultures described recently, suggest that bacteria evolve faster than has been generally recognized. The possibility that amino acid changes occur within protein sequences, without exhibiting any immediately observable phenotype, should be taken into account in studies that involve long-term continuous growth of pure bacterial cultures. The Blc. viridis RC is often studied with sophisticated biophysical techniques and changes such as those described here may well affect their outcome. In other words, there is a danger that laboratory-to-laboratory variation could well be due to different groups not realising that they are actually working with slightly different proteins. A way around this problem is suggested. PMID- 22054236 TI - Pulse monthly steroids during an elective interruption of natalizumab: a post marketing study. AB - BACKGROUND AND PURPOSE: Temporary discontinuation of natalizumab is sometimes considered as the observed risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS). However, interruption of natalizumab may result in a re-start of disease activity. METHODS: In this prospective post-marketing study, 23 patients with MS treated with natalizumab elected a trial of treatment interruption (90-150 days) because of safety concerns on the risk of developing PML. To reduce the risk of disease activity return, patients received monthly intravenous (i.v.) steroid pulses before natalizumab re-start. RESULTS: Despite the steroid coverage, seven patients (30.4%) had an active scan during the natalizumab interruption period; of these, four also had a concomitant clinical exacerbation. CONCLUSIONS: Our findings suggest that i.v. steroids are not currently recommendable as drug coverage during a scheduled treatment interruption period. PMID- 22054237 TI - Sperm-egg interaction. AB - A crucial step of fertilization is the sperm-egg interaction that allows the two gametes to fuse and create the zygote. In the mouse, CD9 on the egg and IZUMO1 on the sperm stand out as critical players, as Cd9(-/-) and Izumo1(-/-) mice are healthy but infertile or severely subfertile due to defective sperm-egg interaction. Moreover, work on several nonmammalian organisms has identified some of the most intriguing candidates implicated in sperm-egg interaction. Understanding of gamete membrane interactions is advancing through characterization of in vivo and in vitro fertilization phenotypes, including insights from less robust phenotypes that highlight potential supporting (albeit not absolutely essential) players. An emerging theme is that there are varied roles for gamete molecules that participate in sperm-egg interactions. Such roles include not only functioning as fusogens, or as adhesion molecules for the opposite gamete, but also functioning through interactions in cis with other proteins to regulate membrane order and functionality. PMID- 22054239 TI - Neurotransmitter corelease: mechanism and physiological role. AB - Neurotransmitter identity is a defining feature of all neurons because it constrains the type of information they convey, but many neurons release multiple transmitters. Although the physiological role for corelease has remained poorly understood, the vesicular uptake of one transmitter can regulate filling with the other by influencing expression of the H(+) electrochemical driving force. In addition, the sorting of vesicular neurotransmitter transporters and other synaptic vesicle proteins into different vesicle pools suggests the potential for distinct modes of release. Corelease thus serves multiple roles in synaptic transmission. PMID- 22054241 TI - Deriving health state utilities for the numerical pain rating scale. AB - BACKGROUND: The use of patient reported outcome measures within cost effectiveness analysis has become commonplace. However, specific measures are required that produce values, referred to as 'utilities', that are capable of generating quality adjusted life years. One such measure - the EQ-5D - has come under criticism due to the inherent limitations of its three-level response scales. In evaluations of chronic pain, the numerical pain rating scale (NPRS) which has eleven levels is routinely used which has a greater measurement range, but which can not be used in cost-effetiveness analyses. This study derived utility values for a series of EQ-5D health states that replace the pain dimensions with the NPRS, thereby allowing a potentially greater range of pain intensities to be captured and included in economic analyses. METHODS: Interviews were undertaken with 100 member of the general population. Health state valuations were elicited using the time trade-off approach with a ten year time horizon. Additionally, respondents were asked where the EQ-5D response scale descriptors of moderate and extreme pain lay on the 11-point NPRS scale. RESULTS: 625 valuations were undertaken across the study sample with the crude mean health state utilities showing a negative non-linear relationship with respect to increasing pain intensity. Relative to a NPRS of zero (NPRS0), the successive pain levels (NPRS1-10) had mean decrements in utility of 0.034, 0.043, 0.061, 0.121, 0.144, 0.252, 0.404, 0.575, 0.771 and 0.793, respectively. When respondents were asked to mark on the NPRS scale the EQ-5D pain descriptors of moderate and extreme pain, the median responses were '4' and '8', respectively. CONCLUSIONS: These results demonstrate the potential floor effect of the EQ-5D with respect to pain and provide estimates of health reduction associated with pain intensity described by the NPRS. These estimates are in excess of the decrements produced by an application of the EQ-5D scoring tariff for both the United States and the United Kingdom. PMID- 22054238 TI - Cell biology and pathology of podocytes. AB - As an integral member of the filtration barrier in the kidney glomerulus, the podocyte is in a unique geographical position: It is exposed to chemical signals from the urinary space (Bowman's capsule), it receives and transmits chemical and mechanical signals to/from the glomerular basement membrane upon which it elaborates, and it receives chemical and mechanical signals from the vascular space with which it also communicates. As with every cell, the ability of the podocyte to receive signals from the surrounding environment and to translate them to the intracellular milieu is dependent largely on molecules residing on the cell membrane. These molecules are the first-line soldiers in the ongoing battle to sense the environment, to respond to friendly signals, and to defend against injurious foes. In this review, we take a membrane biologist's view of the podocyte, examining the many membrane receptors, channels, and other signaling molecules that have been implicated in podocyte biology. Although we attempt to be comprehensive, our goal is not to capture every membrane-mediated pathway but rather to emphasize that this approach may be fruitful in understanding the podocyte and its unique properties. PMID- 22054242 TI - The effects and underlying mechanisms of S-allyl l-cysteine treatment of the retina after ischemia/reperfusion. AB - PURPOSE: Retinal ischemia-associated ocular disorders are vision-threatening. The aim of the present study was to examine whether S-allyl l-cysteine (SAC) is able to protect against retina ischemia/reperfusion injury. METHODS: In vivo, retinal ischemia in the rat was induced by raising intraocular pressure (IOP) to 120 mmHg for 60 min. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating retinal ganglion cell-5 (RGC-5) with 500 MUM H(2)O(2) for 24 h. The mechanisms involved in these processes were evaluated by electrophysiology, immunohistochemistry, and molecular biological approaches. RESULTS: The retinal changes caused by the high IOP were characterized by a decrease in electroretinogram b-wave amplitudes, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, and an upregulation of the mRNA levels of hypoxia-inducible factor-1alpha (HIF-1alpha), vascular endothelium growth factor (VEGF), and matrix metalloproteinase-9 (MMP 9). The increased protein levels of HIF-1alpha, VEGF, and MMP-9 were also seen in RGC-5 cells subjected to defined oxidative stress. Of clinical importance, the ischemic/ischemic-like detrimental effects were concentration-dependently (least effect at 25 MUM) and/or significantly (50 and/or 100 MUM) blunted when SAC was applied 15 min before retinal ischemia or ischemic-like insult, respectively. CONCLUSION: SAC would seem to protect against retinal ischemia by acting as an antioxidant and inhibiting the upregulation of HIF-1alpha, VEGF, and MMP-9. PMID- 22054243 TI - Efficacy of lisdexamfetamine dimesylate in children with attention deficit/hyperactivity disorder previously treated with methylphenidate: a post hoc analysis. AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. Stimulants (methylphenidate [MPH] and amphetamine) are considered first-line ADHD pharmacotherapy. MPH is a catecholamine reuptake inhibitor, whereas amphetamines have additional presynaptic activity. Although MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many still fail to respond optimally to either. After administration, the prodrug stimulant lisdexamfetamine dimesylate (LDX) is converted to l-lysine and therapeutically active d-amphetamine in the blood. The objective of this study was to evaluate the clinical efficacy of LDX in children with ADHD who remained symptomatic (ie, nonremitters; ADHD Rating Scale IV [ADHD-RS-IV] total score > 18) on MPH therapy prior to enrollment in a 4 week placebo-controlled LDX trial, compared with the overall population. METHODS: In this post hoc analysis of data from a multicenter, randomized, double-blind, forced-dose titration study, we evaluated the clinical efficacy of LDX in children aged 6-12 years with and without prior MPH treatment at screening. ADHD symptoms were assessed using the ADHD-RS-IV scale, Conners' Parent Rating Scale Revised short form (CPRS-R), and Clinical Global Impressions-Improvement scale, at screening, baseline, and endpoint. ADHD-RS-IV total and CPRS-R ADHD Index scores were summarized as mean (SD). Clinical response for the subgroup analysis was defined as a >= 30% reduction from baseline in ADHD-RS-IV score and a CGI-I score of 1 or 2. Dunnett test was used to compare change from baseline in all groups. Number needed to treat to achieve one clinical responder or one symptomatic remitter was calculated as the reciprocal of the difference in their proportions on active treatment and placebo at endpoint. RESULTS: Of 290 randomized participants enrolled, 28 received MPH therapy at screening, of which 26 remained symptomatic (ADHD-RS-IV > 18). ADHD-RS-IV total scores, changes from baseline, clinical responsiveness, and rates of symptomatic remission in this subgroup were comparable to the overall population. The safety and tolerability profiles for LDX were comparable to other stimulants currently available. CONCLUSION: In this analysis, children with significant clinical ADHD symptoms despite MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study population. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00556296. PMID- 22054244 TI - Clinical outcomes in kidney transplant recipients receiving long-term therapy with inhibitors of the mammalian target of rapamycin. AB - Inhibitors of the mammalian target of rapamycin (mTOR), sirolimus and everolimus, reduce the incidence of acute rejection following kidney transplantation, but their impact on clinical outcomes beyond 2 years after transplantation is unknown. We examined risks of mortality and allograft loss in a prospective observational study of 993 prevalent kidney transplant recipients who enrolled a median of 72 months after transplantation. During a median follow-up of 37 months, 87 patients died and 102 suffered allograft loss. In the overall population, use of mTOR inhibitors at enrollment was not associated with altered risk of allograft loss, and their association with increased mortality was of borderline significance. However, history of malignancy was the strongest predictor of both mortality and therapy with an mTOR inhibitor. Among patients without a history of malignancy, use of mTOR inhibitors was associated with significantly increased risk of mortality in propensity score-adjusted (hazard ratio [HR] 2.6; 95% CI, 1.2, 5.5; p = 0.01), multivariable-adjusted (HR 3.2; 95% CI, 1.5, 6.5; p = 0.002) and one-to-one propensity score-matched analyses (HR 5.6; 95% CI 1.2, 25.7; p = 0.03). Additional studies are needed to examine the long-term safety of mTOR inhibitors in kidney transplantation, especially among recipients without a history of malignancy. PMID- 22054245 TI - Triple-line behavior and wettability controlled by nanocoated substrates: influence on sessile drop evaporation. AB - In this article, we investigate the influence of the surface properties of substrates on the evaporation process. Using various nanocoatings, it is possible to modify the surface properties of substrates, such as the roughness and the surface energy, while maintaining constant thermal properties. Experiments are conducted under atmospheric conditions with five fluids (methanol, ethanol, propanol, toluene and water) and four coatings (PFC, PTFE, SiOC, and SiO(x)). The various combinations of these fluids and coatings allow for a wide range of drop evaporation properties to be studied: the dynamics of the triple line, the volatility of fluids, and a large range of wettabilities (from 17 to 135 degrees ). The experimental data are in very good quantitative agreement with existing models of quasi-steady, diffusion-driven evaporation. The experimental results show that the dynamics of the evaporative rate are proportional to the dynamics of the wetting radius. Thus, the models succeed in describing the evaporative dynamics throughout the evaporation process regardless of the behavior of the triple line. Moreover, the use of various liquids reveals the validity of the models regardless of their volatility. The results also confirm the recent finding of a universal relation for the time evolution of the drop mass, independent of the drop size and initial contact angle. Finally, this study highlights the separate and coupled roles of the triple line and the wettability on the sessile drop evaporation process. Data reveal that the more wet and pinned a drop, the shorter the evaporation time. PMID- 22054247 TI - A Brave New Year. PMID- 22054246 TI - TOFSIMS-P: a web-based platform for analysis of large-scale TOF-SIMS data. AB - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been a useful tool to profile secondary ions from the near surface region of specimens with its high molecular specificity and submicrometer spatial resolution. However, the TOF-SIMS analysis of even a moderately large size of samples has been hampered due to the lack of tools for automatically analyzing the huge amount of TOF-SIMS data. Here, we present a computational platform to automatically identify and align peaks, find discriminatory ions, build a classifier, and construct networks describing differential metabolic pathways. To demonstrate the utility of the platform, we analyzed 43 data sets generated from seven gastric cancer and eight normal tissues using TOF-SIMS. A total of 87 138 ions were detected from the 43 data sets by TOF-SIMS. We selected and then aligned 1286 ions. Among them, we found the 66 ions discriminating gastric cancer tissues from normal ones. Using these 66 ions, we then built a partial least square-discriminant analysis (PLS-DA) model resulting in a misclassification error rate of 0.024. Finally, network analysis of the 66 ions showed disregulation of amino acid metabolism in the gastric cancer tissues. The results show that the proposed framework was effective in analyzing TOF-SIMS data from a moderately large size of samples, resulting in discrimination of gastric cancer tissues from normal tissues and identification of biomarker candidates associated with the amino acid metabolism. PMID- 22054248 TI - Online Access. PMID- 22054251 TI - Operative Dentistry Home Page. PMID- 22054252 TI - Instructions to Contributors. PMID- 22054253 TI - Serial sections of atrophic acne scars help in the interpretation of microscopic findings and the selection of good therapeutic modalities. AB - BACKGROUND: Acne scar causes problems cosmetically and psychologically. Although microscopic examination of acne scars is a necessity for understanding and treatment of them, and it is not easy to find a paper reporting the microscopic characterization of acne scars. OBJECTIVE: The aim of this study was to examine the microscopic findings of acne scars and to select a good therapeutic modality based on the findings. METHODS: Thirty-one atrophic scars obtained from five patients for cosmesis and 18 serial sections were made from each atrophic scar. The sections were stained with H&E, Masson-trichrome or Verhoeff van Gieson stains. Immunohistochemistry was done with antibodies against transforming growth factor-beta, metalloproteinase-1 (MMP-1), MMP-2, MMP-9 and MMP-13. The stained sections were examined under the microscope. RESULTS: The epidermis of the acne scar was characterized by keratin plugging in the hair follicle orifice (32%) and multi-channelled tracts (29%). The dermis of the acne scar had characteristics including a decrease in the dermal thickness and loss of pilosebaceous units. In addition, inflammatory cell infiltrates were seen in the dermis (77%), and insufficient dense collagen fibre deposition was found in the whole dermis (29%). Other findings such as calcium deposition and foreign body reaction were discovered. CONCLUSION: We have found the characteristics of acne scar through the serial sections of several atrophic scars, and suggest that the treatment must reflect several considerations, including the understanding of histopathological findings and the use of combination therapy. PMID- 22054254 TI - The evolution of cooperative turn-taking in animal conflict. AB - BACKGROUND: A fundamental assumption in animal socio-ecology is that animals compete over limited resources. This view has been challenged by the finding that individuals might cooperatively partition resources by "taking turns". Turn taking occurs when two individuals coordinate their agonistic behaviour in a way that leads to an alternating pattern in who obtains a resource without engaging in costly fights. Cooperative turn-taking has been largely ignored in models of animal conflict and socio-ecological models that explain the evolution of social behaviours based only on contest and scramble competition. Currently it is unclear whether turn-taking should be included in socio-ecological models because the evolution of turn-taking is not well understood. In particular, it is unknown whether turn-taking can evolve when fighting costs and assessment of fighting abilities are not fixed but emerge from evolved within-fight behaviour. We address this problem with an evolutionary agent-based model. RESULTS: We found that turn-taking evolves for small resource values, alongside a contest strategy that leads to stable dominance relationships. Turn-taking leads to egalitarian societies with unclear dominance relationships and non-linear dominance hierarchies. Evolutionary stability of turn-taking emerged despite strength differences among individuals and the possibility to evolve within-fight behaviour that allows good assessment of fighting abilities. Evolutionary stability emerged from frequency-dependent effects on fitness, which are modulated by feedbacks between the evolution of within-fight behaviour and the evolution of higher-level conflict strategies. CONCLUSIONS: Our results reveal the impact of feedbacks between the evolution of within-fight behaviour and the evolution of higher-level conflict strategies, such as turn-taking. Similar feedbacks might be important for the evolution of other conflict strategies such as winner-loser effects or coalitions. However, we are not aware of any study that investigated such feedbacks. Furthermore, our model suggests that turn taking could be used by animals to partition low value resources, but to our knowledge this has never been tested. The existence of turn-taking might have been overlooked because it leads to societies with similar characteristics that have been expected to emerge from scramble competition. Analyses of temporal interaction patterns could be used to test whether turn-taking occurs in animals. PMID- 22054255 TI - RNA binding properties of the US11 protein from four primate simplexviruses. AB - BACKGROUND: The protein encoded by the Us11 gene of herpes simplex viruses is a dsRNA binding protein which inhibits protein kinase R activity, thereby preventing the interferon-induced shut down of protein synthesis following viral infection. Us11 protein is not essential for infectivity in vitro and in mice in herpes simplex virus type 1 (HSV1), however this virus has a second, and apparently more important, inhibitor of PKR activity, the gamma134.5 protein. Recently sequenced simian simplexviruses SA8, HVP2 and B virus do not have an ORF corresponding to the gamma134.5 protein, yet they have similar, or greater, infectivity as HSV1 and HSV2. METHODS: We have expressed the US11 proteins of the simplexviruses HSV1, HSV2, HVP2 and B virus and measured their abilities to bind dsRNA, in order to investigate possible differences that could complement the absence of the gamma134.5 protein. We employed a filter binding technique that allows binding of the Us11 protein under condition of excess dsRNA substrate and therefore a measurement of the true Kd value of Us11-dsRNA binding. RESULTS AND CONCLUSIONS: The results show a Kd of binding in the range of 0.89 nM to 1.82 nM, with no significant difference among the four Us11 proteins. PMID- 22054256 TI - Hypervigilance or avoidance of trigger related cues in migraineurs? - a case control study using the emotional stroop task. AB - BACKGROUND: "Negative affect" is one of the major migraine triggers. The aim of the study was to assess attentional biases for negative affective stimuli that might be related to migraine triggers in migraine patients with either few or frequent migraine and healthy controls. METHODS: Thirty-three subjects with frequent migraine (FM) or with less frequent episodic migraine, and 20 healthy controls conducted two emotional Stroop tasks in the interictal period. In task 1, general affective words and in task 2, pictures of affective faces (angry, neutral, happy) were used. For each task we calculated two emotional Stroop indices. Groups were compared using one-way ANOVAs. RESULTS: The expected attentional bias in migraine patients was not found. However, in task 2 the controls showed a significant attentional bias to negative faces, whereas the FM group showed indices near zero. Thus, the FM group responded faster to negative than to positive stimuli. The difference between the groups was statistically significant. CONCLUSIONS: The findings in the FM group may reflect a learned avoidance mechanism away from affective migraine triggers. PMID- 22054257 TI - Portal venous versus systemic venous drainage of pancreas grafts: impact on long term results. AB - Portal venous (PV) and systemic venous (SV) drainage methods are used in pancreas transplantation. The impact of the reconstruction technique on long-term outcome remains unclear. We compared the efficacy and side effects of both methods in 192 recipients who received synchronous pancreas kidney transplants between November 1995 and November 2007. SV and PV drainage were used in 147 and 45 cases, respectively. Pancreas function was determined by hemoglobin A1c levels and annual oral glucose tolerance test. Serum creatinine assessed kidney function. Serum lipid (low-density lipoprotein, high-density lipoprotein and cholesterol) levels and body mass index were measured annually. Patient and graft survival were calculated by log-rank analysis. Pancreas survival for SV versus PV patients was similar after 5 years (81.8% vs. 75.5%) and 10 years (65.1% vs. 60%; p = NS). Similarly, no difference was detected between the groups regarding kidney survival after 5 years (92.9% vs. 84.4%) and 10 years (81.6% vs. 75.5%; p = NS). Patient survival did not differ at 5 years (94.3% vs. 88.8%) and 10 years (85.1% vs. 84.4%; p = NS). Pancreas and kidney function and the lipid profiles were similar in both groups. SV and PV drainage of pancreas grafts offer similar long term graft survival and function and choice of method should remain the preference of the surgeon. PMID- 22054258 TI - Intra- and interspecies variation in bioconcentration potential of polychlorinated biphenyls: are all lipids equal? AB - The variation among bioconcentration factors (BCFs) available in the literature is commonly ascribed to experimental parameters and metabolic capacity. Though bioconcentration is generally considered to be governed by partitioning processes and therefore to depend on the composition of the partition phases, the effect of lipid composition on BCFs measured for hydrophobic organic chemicals has largely escaped attention. The reason may be that the effect cannot easily be studied separately in a conventional BCF test setup and that any subtle effects will often be obscured by the variation normally observed when working with living organisms. In the present study, this variation was circumvented by substituting biota with biological homogenates, which allowed measuring chemical partitioning in a fashion that has proved successful for many other environmental matrixes (e.g., sediments, soils, carbonaceous materials). The appropriateness of using a homogenate as a representation of the organism from which it was derived was demonstrated by a good agreement between homogenate-water partition coefficients (or necroconcentration factors; NCFs) and actual BCFs for PCBs and aquatic worms. Subsequent experiments focused on the intra- and interspecies differences in lipid-normalized NCFs. Intraspecies variation was studied for aquatic worms and sticklebacks, which were acclimatized at different temperatures (5-24 degrees C), whereas interspecies variation was investigated by determining NCFs for eight different aquatic species. Although temperature-induced intraspecies differences were subtle (<0.16 log units), interspecies differences among lipid-normalized NCFs were as high as 0.9 log units, with homogenates of "simple" organisms showing a lower sorption capacity than those of the more "complex" species. These results suggest that the variation observed in the literature BCFs may partly be caused by differences in lipid composition and contest the usefulness of the common practice of applying generic BCFs in risk assessment of chemicals. PMID- 22054259 TI - Soyabean glyceollins: biological effects and relevance to human health. AB - Glyceollins, one family of phytoalexins, are de novo synthesised from daidzein in the soyabean upon exposure to some types of fungus. The efficiency of glyceollin production appears to be influenced by soyabean variety, fungal species, and the degree of physical damage to the soyabean. The compounds have been shown to have strong antioxidant and anti-inflammatory activities, and to inhibit the proliferation and migration of human aortic smooth muscle cells, suggesting their potential to prevent atherosclerosis. It has also been reported that glyceollins have inhibited the growth of prostate and breast cancer cells in xenograft animal models, which is probably due to their anti-oestrogenic activity. In essence, glyceollins deserve further animal and clinical studies to confirm their health benefits. PMID- 22054260 TI - Antioxidant, nitric oxide scavenging and malondialdehyde scavenging activities of essential oils from different chemotypes of Zataria multiflora. AB - The antioxidant, nitric oxide (NO) scavenging and malondialdehyde (MDA) scavenging activities of different Zataria multiflora (ZM) chemotype essential oils (EOs) were investigated. The main components are: ZM1 (carvacrol, p-cymene), ZM2 (carvacrol, p-cymene), ZM3 (carvacrol, p-cymene), ZM4 (linalool), ZM5 (carvacrol, p-cymene, thymol), ZM6 (thymol, carvacrol, p-cymene, gamma terpienene), ZM7 (thymol, p-cymene, gamma-terpienene) and ZM8 (carvacrol, linalool, p-cymene, thymol). The antioxidant capacities were estimated to be 863 +/- 55, 619 +/- 27, 876 +/- 32, 38 +/- 9, 649 +/- 50, 595 +/- 40, 696 +/- 41 and 618 +/- 9 ug ascorbic acid equivalents per millilitre for ZM1 to ZM8, respectively. The NO scavenging values were estimated to be 54 +/- 1.2, 50 +/- 1.4, 63 +/- 1, 0.60 +/- 0.1, 53 +/- 0.7, 53 +/- 1.5, 38 +/- 1.1 and 46.5 +/- 3 ug ascorbic acid equivalents per millilitre for ZM1 to ZM8, respectively. The MDA scavenging values were estimated to be 19 +/- 1, 9 +/- 1, 24 +/- 1, 1.6 +/- 0.6, 12 +/- 1, 11.7 +/- 1, 10 +/- 1 and 12.5 +/- 1.3 ug ascorbic acid equivalents per millilitre for ZM1 to ZM8, respectively. Among these EOs, ZM3 with carvacrol and p-cymene had higher antioxidant, NO scavenging and MDA scavenging properties. PMID- 22054261 TI - A novel liposome surface modification agent that prolongs blood circulation and retains surface ligand reactivity. AB - Liposomes are recognized as potentially useful drug carriers but many problems preclude practical medical application. Liposomes bind with serum proteins (opsonization) and are captured by the reticuloendothelial system cells in the liver and spleen, which limits their ability to deliver drugs to other target sites. Modification of lipids with flexible, hydrophilic polymers such as poly(ethylene glycol) (PEG) to yield sterically stabilized liposomes is one approach to improve liposome blood circulation and tissue distribution properties. In this study, we examined liposomes prepared using lipids modified with a new branched oligoglycerol (BGL) moiety for steric stabilization. This novel BGL comprised 14 glycerol units (termed BGL014) connected with flexible ether linkages, resulting in a branched cascade-like structure that is highly expanded in aqueous solution. BGL014 was coupled to 1,2 distearoylphosphatidylethanolamine to yield BGL014-modified lipids. Incorporation of BGL014 into liposomes (BGL014L) resulted in long blood circulation times, despite a much thinner fixed aqueous layer thickness compared to PEG formulations. BGL014 produced a liposome surface coating that appears to function through steric inhibition of non-specific protein binding without strong interference of specific protein-binding reactions. Liposome structure and functionality was maintained following BGL014-modification, as the incorporation ratio of drug remained high. These results suggest that the BGL014 modification of liposomes is a promising approach to produce stable and long circulating drug carriers capable of selective binding to specific proteins. PMID- 22054262 TI - Determination of the purity of cucurbit[n]uril (n = 7, 8) host samples. AB - The formation of highly stable inclusion complexes in aqueous solution between the organometallic cobaltocenium cation (Cob(+)) and the hosts cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) was used to develop a simple method, based on UV vis titrations, to assay the purity of samples of these two hosts. The equilibrium association constant (K) of the Cob(+)@CB7 complex had been previously reported by our group as 5.7 * 10(9) M(-1) at 25 degrees C in 50 mM sodium acetate medium. In this work, we determine a K value of 1.9 * 10(8) M(-1) at 25 degrees C in the same medium for the Cob(+)@CB8 complex. The high stability of these complexes and their decreased molar absorptivity coefficients (at 261 nm), compared to that for free Cob(+), lead to straightforward titration plots when graphing absorbance versus concentration of added CB7 (or CB8) host, at constant Cob(+) concentration. PMID- 22054263 TI - Accurate guidance of a catheter by ultrasound imaging and identification of a catheter tip by pulsed-wave Doppler. AB - BACKGROUND: With the advent of numerous minimally invasive medical procedures, accurate catheter guidance has become imperative. We introduce and test an approach for catheter guidance by ultrasound imaging and pulsed-wave (PW) Doppler. METHODS: A steerable catheter is fitted with a small piezoelectric crystal at its tip that actively transmits signals driven by a function generator. We call this an active-tip (AT) catheter. In a water tank, we immersed a "target" crystal and a rectangular matrix of four "reference" crystals. Two dimensional (2D) ultrasound imaging was used for initial guidance and visualization of the catheter shaft, and then PW Doppler mode was used to identify the AT catheter tip and guide it to the simulated target that was also visible in the 2D ultrasound image. Ten guiding trials were performed from random initial positions of the AT catheter, each starting at approximately 8 cm from the target. RESULTS: After the ten navigational trials, the average final distance of the catheter tip from the target was 2.4 +/- 1.2 mm, and the range of distances from the trials was from a minimum of 1.0 mm to a maximum of 4.5 mm. CONCLUSIONS: Although early in the development process, these quantitative in vitro results show promise for catheter guidance with ultrasound imaging and tip identification by PW Doppler. PMID- 22054264 TI - Should we prevent colorectal cancer? PMID- 22054265 TI - Stenosis in laparoscopic gastric bypass: management by endoscopic dilation without fluoroscopic guidance. AB - OBJECTIVES: gastric bypass is the surgical procedure that is carried out most frequently in the treatment of morbid obesity. Stenosis of the gastro-jejunal anastomosis is a relatively frequent complication that requires endoscopic management. However, the optimal dilation technique is yet to be determined. The purpose of this study was to evaluate the safety and efficacy of dilation with a hydrostatic balloon (CRE) without radioscopic guidance in morbidly obese patients treated by laparoscopic bypass. MATERIAL AND METHODS: retrospective review of the data elicited from 525 patients treated against morbid obesity with laparoscopic gastric bypass from January, 2006 to November, 2010. RESULTS: a total of 22/525 patients (4.1%) developed stenosis of the anastomosis [20 women (91%), 2 men (9%)]. In four patients (18.2%), there was an associated anastomotic ulcer, and in one case, there was a history of bleeding of an ulcer treated with sclerosis one month earlier. The diagnosis of stenosis was done in most patient during the first 90 days after the bypass. All cases were resolved by means of endoscopic dilation without adioscopic guidance, 15 cases (68.1%) required a single session, 6 cases (27.2%) two sessions, and 1 case (4.5%) required four sessions. This last case had an associated anastomotic ulcer. The diameter of the balloons ranged from 12 to 20 mm, generally using diameters of 12-15 mm in the first session, and increasing them in the following sessions according to the previous result. One patient treated with a 20 mm balloon presented with a small tear, without showing any evidence of leak of contrast medium in the radioscopic guidance, and was thus managed conservatively. In the follow-up, no re-stenoses were detected. CONCLUSIONS: in our experience, stenosis of the anastomosis in the laparoscopic gastric bypass is an infrequent complication. When it happens, dilation with a hydrostatic balloon is an effective and safe treatment. Radioscopic guidance during dilation is not strictly necessary if norms of progressive dilation are followed. PMID- 22054266 TI - Omega 3 fatty acids supplementation has an ameliorative effect in experimental ulcerative colitis despite increased colonic neutrophil infiltration. AB - PURPOSE: omega 3 polyunsaturated fatty acids have anti-inflammatory properties and can be beneficial in the treatment of inflammatory diseases, such as ulcerative colitis. Dextran sodium sulphate (DSS) colitis in rats appears to mimic nearly all of the morphological characteristics and lesion distributions of ulcerative colitis. The purpose of the current study was to investigate the efficacy of omega 3 fatty acids in the treatment of experimental ulcerative colitis. METHODS: thirty-six Wistar rats were randomly assigned to group A or group B receiving 5% dextran sulfate sodium (DSS) in their drinking water for eight days. For the next eight days post-DSS, group A animals received tap-water, and group B animals were fed a nutritional solution containing high levels of omega 3 polyunsaturated fatty acids (ProSure(r), Abbott Laboratories, Zwolle, Netherlands) once per day, administrated with a orogastric feeding tube. RESULTS: animals fed an omega 3 rich diet exhibited a statistically significant increase in hematocrit and hemoglobin levels, compared to animals drinking tap water, and a trend towards histopathological and clinical improvement, with the administration of omega 3 fatty acids ameliorating epithelial erosion by day 8 post-DSS, but no statistically significant difference was observed between group A and group B animals at 4 or 8 days post-DSS. Also, a statistically significant increase in neutrophil infiltration was observed, as depicted by myelohyperoxidase activity. CONCLUSION: our findings support a positive role of omega 3 polyunsaturated fatty acids supplementation in an experimental model of ulcerative colitis despite the increased colonic neutrophil infiltration. Further studies are needed in order to investigate the role of increased neutrophils in colonic mucosa. PMID- 22054267 TI - Effects of changes in dietary habits on colorectal cancer incidence in twenty countries from four continents during the period 1971-2002. AB - INTRODUCTION: the incidence of colorectal cancer is one of the highest on a global level. Many epidemiological studies have identified risk and protective factors, many of which have a behavioral component and, therefore, are potentially avoidable or subject to modification. This study investigated the incidence rates of colorectal cancer by gender in twenty different countries, taking into account the dietary habits of the habitants of each country. MATERIAL AND METHODS: adjusted incidence rates, according to gender, were obtained for each country from the International Agency for Research on Cancer during the period 1971-2002.Annual per capita consumption data of the different dietary variables were obtained for the period 1961-2007 from the Food and Agriculture Organization of the United Nations. Pearson's correlation coefficients were calculated comparing incidence rates according to gender with different dietary variable using ten-year delay intervals. RESULTS: there is an important variation in trends of colorectal cancer incidence worldwide which were found to be related with the dietary habits of each country. DISCUSSION: based on the trends observed, each country was classified into one of four different situations based on the range of values of their incidence rates and linear trends observed. Due to the potential of primary prevention programs for colorectal cancer and to the delay between changes in the exposure to risk and protective factors and the effects on the incidence of this tumor, the application of legislative and educational measures promoting a healthy diet has become an urgent issue to stop the increasing tendency of colorectal cancer reported worldwide. PMID- 22054268 TI - Asymptomatic hypertransaminasemia in patients in primary care. AB - INTRODUCTION AND OBJECTIVE: asymptomatic hypertransaminasemia (AH) is a common finding in clinical practice. We propose to determine the prevalence of AH in our environment, its epidemiology and its evolution. MATERIAL AND METHODS: we studied a random sample of 1,136 blood tests undertaken in 2006, excluding patients with known hepatic disease or symptoms or signs of liver disease, and following the evolution of the AHs until 2009. Data was analyzed using bivariate and multivariate logistic regression. RESULTS: the percentage of patients found with a AH was 15.24% (95% CI 13.52 to 16.96%). The rates of AST and ALT, were 6.93% (95% CI 5.71 to 8.15%) and 14.31% (95% CI 12.65 to 15.97%) respectively. The percentage of normalization of transaminase values in a second analytical control was a 31.81% (95% CI: 26.21 to 37.4%). An association was found between AH and BMI (OR: 1.129, 95% CI 1.062 to 1.199) and between the persistence of AH and GGT (OR: 1.011, 95% CI 1.003 to 1.018). Fundamental tests such as hepatitis serology or ultrasound were performed on only 50% of patients (with 32% of steatohepatitis). CONCLUSIONS: the prevalence found in our study of AH was relatively high (15.24%), being more frequently encountered in obese subjects. Nearly a third of the AHs is normalized in a subsequent blood test. The high GGT is associated with persistence of AH. There is great variability in terms of additional testing in patients with AH and the application of such tests is not protocol. PMID- 22054269 TI - Experimental models for hepatic encephalopathy. PMID- 22054270 TI - Obturator hernia responsible for intestinal obstruction. PMID- 22054271 TI - Atypical endoscopic findings of Crohn's disease. PMID- 22054272 TI - Fitz-Hugh-Curtis syndrome: abdominal pain in women of 26 years old. AB - Fitz-Hugh-Curtis syndrome is an inflammation of the liver capsule as a complication of pelvic inflammatory disease, whose etiologic agent is the most common C. trachomatis. The acute phase Fitz-Hugh-Curtis syndrome may present with pain in upper right quadrant abdomen, commonly confused with other diseases of the hepatobiliary and gastrointestinal tract. Definitive diagnosis is now possible for non-invasive techniques such as ultrasound, computed tomography, as well as techniques for the isolation of the germ responsible available in most centers. PMID- 22054273 TI - [Information for patients. Treatment of acute hepatitis C]. PMID- 22054274 TI - Subcapsular hepatic hematoma after ERCP (endoscopic retrograde cholangipancreatography). PMID- 22054275 TI - Association of Wilson disease with neurofibromatosis. PMID- 22054276 TI - Rectal ulcer induced by suppositories. PMID- 22054277 TI - Chagas disease in the differential diagnosis of megacolon. PMID- 22054278 TI - Romiplostim in chronic liver disease with severe thrombocytopenia undergoing an elective invasive procedure. PMID- 22054279 TI - Avascular necrosis of the knees and ulcerative colitis. PMID- 22054281 TI - 'Face-lift' PMID- 22054280 TI - Judgement of discrete and continuous quantity in adults: number counts! AB - Three experiments involving a Stroop-like paradigm were conducted. In Experiment 1, adults received a number comparison task in which large sets of dots, orthogonally varying along a discrete dimension (number of dots) and a continuous dimension (cumulative area), were presented. Incongruent trials were processed more slowly and with less accuracy than congruent trials, suggesting that continuous dimensions such as cumulative area are automatically processed and integrated during a discrete quantity judgement task. Experiment 2, in which adults were asked to perform area comparison on the same stimuli, revealed the reciprocal interference from number on the continuous quantity judgements. Experiment 3, in which participants received both the number and area comparison tasks, confirmed the results of Experiments 1 and 2. Contrasting with earlier statements, the results support the view that number acts as a more salient cue than continuous dimensions in adults. Furthermore, the individual predisposition to automatically access approximate number representations was found to correlate significantly with adults' exact arithmetical skills. PMID- 22054283 TI - Assessment of D216H DYT1 polymorphism in a Chinese primary dystonia patient cohort. AB - BACKGROUND: The D216H single-nucleotide polymorphism (SNP) (rs1801968) in DYT1 exon 4 has been suggested to be a genetic modifier in primary dystonia. METHODS: To further explore this question, we assessed rs1801968 variations in a cohort of 210 Chinese patients with primary dystonia devoid of DYT1 mutations. RESULTS: We found that focal dystonia, specifically cervical dystonia, was the most common form of dystonia, with 8.1% of all the patients having a positive family history of dystonia. No association of the D216H SNP with primary dystonia was identified. In a subsequent subgroup analysis, the 216H allele was found to occur more frequently in patients with writer's cramp, but no correlation was found between the allele and other forms of dystonia or age of onset. CONCLUSIONS: Our findings do not confirm that the allele contributes to the risk of D216H SNP primary dystonia. PMID- 22054284 TI - The p101 subunit of PI3Kgamma restores activation by Gbeta mutants deficient in stimulating p110gamma. AB - G-protein-regulated PI3Kgamma (phosphoinositide 3-kinase gamma) plays a crucial role in inflammatory and allergic processes. PI3Kgamma, a dimeric protein formed by the non-catalytic p101 and catalytic p110gamma subunits, is stimulated by receptor-released Gbetagamma complexes. We have demonstrated previously that Gbetagamma stimulates both monomeric p110gamma and dimeric p110gamma/p101 lipid kinase activity in vitro. In order to identify the Gbeta residues responsible for the Gbetagamma-PI3Kgamma interaction, we examined Gbeta1 mutants for their ability to stimulate lipid and protein kinase activities and to recruit PI3Kgamma to lipid vesicles. Our findings revealed different interaction profiles of Gbeta residues interacting with p110gamma or p110gamma/p101. Moreover, p101 was able to rescue the stimulatory activity of Gbeta1 mutants incapable of modulating monomeric p110gamma. In addition to the known adaptor function of p101, in the present paper we show a novel regulatory role of p101 in the activation of PI3Kgamma. PMID- 22054285 TI - Do diabetes and depressed mood affect associations between obesity and quality of life in postmenopause? Results of the KORA-F3 Augsburg population study. AB - BACKGROUND: To assess associations of obesity with health-related quality of life (HRQL) in postmenopausal women, and whether depressed mood and diabetes moderate these associations. METHODS: Survey of 983 postmenopausal women aged 35-74, general population, Augsburg region/Germany, 2004/2005. Body weight/height and waist/hip circumference were assessed anthropometrically and classified via BMI >= 30 as obese, and WHR >= 0.85 as abdominally obese (vs. not). Depressed mood was assessed by the Depression and Exhaustion-(DEEX-)scale, diabetes and postmenopausal status by self-report/medication, and HRQL by the SF-12. RESULTS: General linear models revealed negative associations of obesity and abdominal obesity with physical but not mental HRQL. Both forms of excess weight were associated with diabetes but not depressed mood. Moderation depended on the HRQL domain in question. In non-diabetic women, depressed mood was found to amplify obesity-associated impairment in physical HRQL (mean "obese"-"non-obese" difference given depressed mood: -6.4, p < .001; among those without depressed mood: -2.5, p = .003). Reduced mental HRQL tended to be associated with obesity in diabetic women (mean "obese"-"non-obese" difference: -4.5, p = .073), independent of depressed mood. No interactions pertained to abdominal obesity. CONCLUSIONS: In postmenopausal women, depressed mood may amplify the negative impact of obesity on physical HRQL, while diabetes may be a precondition for some degree of obesity-related impairments in mental HRQL. PMID- 22054286 TI - Bortezomib mitigates adverse prognosis conferred by Bcl-2 overexpression in patients with relapsed/refractory multiple myeloma. AB - Overexpression of the Bcl-2 family of genes results in increased transcription of anti-apoptotic proteins. In vitro data suggest that this may enhance acquired chemoresistance and correlate with extramedullary invasion. This has led to pursuing the Bcl-2 family of proteins as therapeutic targets in several malignant disorders, including multiple myeloma (MM). The impact of novel therapeutic agents such as bortezomib on these molecular markers is not known. We investigated the association between the expression of anti-apoptotic members of the Bcl-2 family and the efficacy of bortezomib in patients with relapsed/refractory MM. Gene expression data generated prospectively from large clinical trials were utilized. Hypothesis testing using a multisample test for equivalence was performed. The association between Bcl-2 expression levels and clinical response was negated in bortezomib-treated patients (p = 0.014), while not so in dexamethasone-treated patients (p = 0.92). Similar results were noted for variant 2 of the Mcl-1 gene (p = 0.003). Results for Bcl-xl did not meet the level of significance. Thus, the importance of the Bcl-2 family of proteins as prognostic markers in MM should be reassessed in the novel therapeutic agent era. Our data suggest that bortezomib may overcome the prognostic effect conferred by overexpression of some of the anti-apoptotic Bcl-2 family of genes in patients with relapsed/refractory MM. PMID- 22054287 TI - Survey and analysis of the efficacy and prescription pattern of sorafenib in patients with acute myeloid leukemia. AB - Sorafenib is a multi-kinase inhibitor with activity against several intracellular kinases which may play a role in the pathogenesis of acute myeloid leukemia (AML). In vitro data and results from early clinical trials suggest that sorafenib might be an effective drug for the treatment of AML. However, clinical data are still sparse, and there are only a few reported cases of monotherapy. The aim of the present research was to collect clinical data on efficacy and safety in a systematic way by conducting a survey on clinical experience with sorafenib. Thirty institutions were asked to document all patients treated with sorafenib diagnosed with AML. Of all 29 evaluable patients, six (21%) responded to sorafenib containing treatment by achieving a complete remission (CR, n = 2) or complete remission with incomplete platelet recovery (CRi, n = 4). In 23 patients receiving sorafenib as monotherapy, the CRi rate amounted to 13% and no CRs were documented. Of the 18 FLT-ITD positive patients with sorafenib monotherapy, two patients achieved a CRi (11%). In five FLT3-ITD negative cases, one CRi was documented (20%). Our results suggest the potential ability of the drug to induce remissions in refractory or relapsed AML even when given as monotherapy. PMID- 22054288 TI - Posterior reversible encephalopathy syndrome in a patient with multiple myeloma treated with thalidomide. PMID- 22054291 TI - Operative Dentistry Home Page. PMID- 22054289 TI - Effect of homoharringtonine on bone marrow CD34 + CD117 + cells in patients with chronic myelogenous leukemia. AB - This study investigated the effect of homoharringtonine (HHT) on bone marrow CD34 + CD117 + cells in patients with chronic myelogenous leukemia (CML). Fifty-seven patients with CML who could not receive either imatinib or interferon-alpha were treated with HHT (n = 31) or hydroxycarbamide (HU) (n = 26) to induce and maintain remission, and bone marrow CD34 + CD117 + cells were assayed with flow cytometry. The proportion of CD34 + CD117 + cells was higher in untreated patients (24.7 +/- 6.4%) than in donors (4.4 +/- 1.1%) and decreased remarkably in patients who had hematological remission (11.2 +/- 3.1%) and cytogenetic response (8.9 +/- 3.1%) as compared with those without (27.8 +/- 7.3% and 18.5 +/ 5.3%, respectively) at 12 months after therapy. The hematological remission rate for patients with proportion of CD34 + CD117 + cells >= 20% prior to treatment was lower (41.7%) than in patients with CD34 + CD117 + cells < 20% (78.9%; p < 0.05). However, there was no such difference of CD34 + CD117 + cell percentage in the HU group. It can be concluded that high expression of CD117 on CD34 + cells is a marker of poor prognosis and is also a target for the anti-CML effect of HHT. PMID- 22054294 TI - Corporate Sponsorship. PMID- 22054293 TI - Instructions to Contributors. PMID- 22054295 TI - Iron oxide nanomatrix facilitating metal ionization in matrix-assisted laser desorption/ionization mass spectrometry. AB - The significance and epidemiological effects of metals to life necessitate the development of direct, efficient, and rapid method of analysis. Taking advantage of its simple, fast, and high-throughput features, we present a novel approach to metal ion detection by matrix-functionalized magnetic nanoparticle (matrix@MNP) assisted MALDI-MS. Utilizing 21 biologically and environmentally relevant metal ion solutions, the performance of core and matrix@MNP against conventional matrixes in MALDI-MS and laser desorption ionization (LDI) MS were systemically tested to evaluate the versatility of matrix@MNP as ionization element. The matrix@MNPs provided 20- to >100-fold enhancement on detection sensitivity of metal ions and unambiguous identification through characteristic isotope patterns and accurate mass (<5 ppm), which may be attributed to its multifunctional role as metal chelator, preconcentrator, absorber, and reservoir of energy. Together with the comparison on the ionization behaviors of various metals having different ionization potentials (IP), we formulated a metal ionization mechanism model, alluding to the role of exciton pooling in matrix@MNP-assisted MALDI-MS. Moreover, the detection of Cu in spiked tap water demonstrated the practicability of this new approach as an efficient and direct alternative tool for fast, sensitive, and accurate determination of trace metal ions in real samples. PMID- 22054296 TI - Anatomical relations of the superficial sensory branches of the radial nerve: a cadaveric study with clinical implications. AB - BACKGROUND: Anatomically, it is difficult to give a systematic description of the superficial branch of the radial nerve (SBRN). Our aim was to describe the exact relationship of the SBRN to fixed bony points of radial styloid and Lister's tubercle, and to the cephalic vein. We also compared our data with other international studies. METHODS: The study was a descriptive anatomical study. Twenty-five forearms were dissected. Measurements were made from predefined fixed reference points. RESULTS: The mean distance to the point of emergence of the nerve from the radial styloid was 8.54 cm (SD = 1.32). The nerve branched at a mean distance of 5.57 cm (SD = 1.43) from the radial styloid. The mean distance to the point where the most medial and most lateral branches of the nerve crossing the wrist joint, measured from the Lister's tubercle were 2.51 cm (SD = 0.53) and 3.90 cm (SD = 0.64). In 17 specimens(68%) cephalic vein crossed the SBRN superficially once. Mean distance from the radial styloid to the most distal point where the vein crossed the nerve was 5.10 cm. Diffefrence between mean distance to the point of emergence and branching point, when compared with other international studies were not statistically significant. (P value > 0.05) CONCLUSIONS: We recommend avoiding transverse incisions in the snuffbox region between 2.51 cm and 3.90 cm from the Listers tubercle. We also recommend avoiding cannulation of the cephalic vein in the distal forearm. PMID- 22054297 TI - Effects of forage type, body condition and single-nucleotide polymorphisms in the bovine cytochrome P450 regulatory region on cow productivity. AB - Single-nucleotide polymorphisms (SNP) in the coding sequence of cytochrome p450 (CYP3A28) have been associated with milk yield and composition, and calving traits in cows. In this study, we aimed to determine whether (i) the CYP3A28 regulatory region was polymorphic and (ii) SNP genotype, forage type, body condition and their interactions affect cow productivity. Primers for CYP3A28 promoter were designed to amplify a 483-bp segment by PCR. Amplicon sequences revealed seven SNP (T-318C, T-113A, C-189T, T-78G, A6G, G17A and T21C) in Brahman (38 cows), Brahman x Angus reciprocal crosses (47 cows) and crossbreds (98 cows). Angus cows (n = 41) appeared to be fixed at those SNP locations. Genotype and forage {endophyte-infected tall fescue [KY+; Lolium arundinaceum (Schreb.) S. J. Darbyshire] vs. bermudagrass [Cynodon dactylon (L.) Pers.]} effects on lifetime (8-years) calving rate, and calf weaning weights and heights were determined in Herd 1 (126 cows); genotype and BC (low vs. moderate) effects on calving date and calving percent were determined in Herd 2 (98 cows). Four SNP (T-318C, T-113A, A06G and T21C) appeared to be related to cattle productivity, CC cows at T-318C having a lower (p < 0.05) lifetime calving rate than TC or TT cows (65%, 85% and 81% respectively). Cows that grazed KY+ and were TT at T-318C produced calves that tended (p < 0.07) to weigh less than their contemporaries. Moreover, calves of TT cows were shorter (p < 0.05) at weaning than calves of CC or TC cows. In Herd 2, moderate-BC cows that were TT or AA at T-318C, T-113A, T-78G, A6G and T21C had greater (p < 0.05) calving rates (74-80%) than heterozygous cows (46 60%), and low-BC cows that were AA at G17A calved at least 6 days earlier (p < 0.05) than heterozygous cows. Our findings suggest that SNP in the CYP3A28 regulatory region of Brahman-influenced cows are associated with cattle productivity. PMID- 22054298 TI - Home and away- the evolutionary dynamics of homing endonucleases. AB - BACKGROUND: Homing endonucleases (HEases) are a large and diverse group of site specific DNAases. They reside within self-splicing introns and inteins, and promote their horizontal dissemination. In recent years, HEases have been the focus of extensive research due to their promising potential use in gene targeting procedures for the treatment of genetic diseases and for the genetic engineering of crop, animal models and cell lines. RESULTS: Using mathematical analysis and computational modeling, we present here a novel account for the evolution and population dynamics of HEase genes (HEGs). We describe HEGs as paradoxical selfish elements whose long-term persistence in a single population relies on low transmission rates and a positive correlation between transmission efficiency and toxicity. CONCLUSION: Plausible conditions allow HEGs to sustain at high frequency through long evolutionary periods, with the endonuclease frequency being either at equilibrium or periodically oscillating. The predictions of our model may prove important not only for evolutionary theory but also for gene therapy and bio-engineering applications of HEases. PMID- 22054299 TI - Does the use of mTOR inhibitors increase long-term mortality in kidney recipients? PMID- 22054300 TI - Viscoelastic property mapping with contact resonance force microscopy. AB - We demonstrate the accurate nanoscale mapping of near-surface loss and storage moduli on a polystyrene-polypropylene blend with contact resonance force microscopy (CR-FM). These viscoelastic properties are extracted from spatially resolved maps of the contact resonance frequency and quality factor of the AFM cantilever. We consider two methods of data acquisition: (i) discrete stepping between mapping points and (ii) continuous scanning. For point mapping and low speed scanning, the values of the relative loss and storage modulus are in good agreement with the time-temperature superposition of low-frequency dynamic mechanical analysis measurements to the high frequencies probed by CR-FM. PMID- 22054301 TI - Kinetic and mechanistic insight into the thermodynamic degradation of saxagliptin. AB - The dipeptidyl peptidase-IV inhibitor saxagliptin (Onglyza) can undergo a thermodynamically favored cyclization to form the corresponding cyclic amidine. The kinetics and mechanism of this conversion were examined to develop a commercial synthesis that afforded saxagliptin with only trace levels of this key byproduct. Important findings of this work are the identification of a profound solvent effect and the determination of an autocatalytic pathway. Both of these phenomena result from transition structures involving proton transfer. PMID- 22054302 TI - Physicochemical and toxicological properties of commercial carbon blacks modified by reaction with ozone. AB - Ozonation of two commercial carbon blacks (CBs), Printex 90 (P90) and Flammruss 101 (F101), was carried out and changes in their morphology, physical properties, and cytotoxicity were examined. The hypothesis examined was that different methods of manufacture of CBs influence their chemical reactivity and toxicological properties. Structural changes were examined by X-ray photoelectron spectroscopy, infrared spectroscopy, Raman spectroscopy, and electron paramagnetic resonance spectroscopy (EPR). Introduction of surface oxygen functionality upon ozonation led to changes in surface charge, aggregation characteristics, and free radical content of the CBs. However, these changes in surface functionality did not alter the cytotoxicity and release of inflammation markers upon exposure of the CBs to murine macrophages. Interaction of macrophages with F101 resulted in higher levels of inflammatory markers than P90, and the only structural correlation was with the higher persistent radical concentration on the F101. PMID- 22054303 TI - Exhaled nitric oxide in diagnosis of bronchiolitis obliterans syndrome in lung transplant recipients: possible limitations. PMID- 22054304 TI - Factors associated with antenatal mental disorder in West Africa: a cross sectional survey. AB - BACKGROUND: Maternal mental illness is likely to have a profound impact in less developed parts of the world. A mother experiencing mental illness in a low income setting is at risk of providing sub-optimal care for her offspring which can have grave consequences in an environment where poverty, overcrowding, poor sanitation, malnutrition, tropical diseases and a lack of appropriate medical services may be pronounced. Given the profound consequences of antenatal and postnatal mental illness on maternal mental health, foetal wellbeing and childhood growth and development the factors associated with mental illness in a Sub-Saharan setting merit clarification and investigation. METHODS: A prospective survey design was conducted in Lagos. Self reporting questionnaire 20 items - SRQ20 - assessed the presence of mental illness. The WHO Multi-country Study on Women's Health and Domestic Violence Questions assessed women's exposure to violence. Numerous variables potentially associated with mental illness including maternal socio-economic factors, maternal characteristics, obstetric variables and the characteristics of previous children were recorded. Direct logistic regression was performed to assess the impact of a number of variables on the likelihood of presence of mental disorder in the population. RESULTS: 189 women were surveyed. 7% met the criteria for experiencing a common mental disorder according to their score on the SRQ-20. Of variables examined only the number of female children and the presence of inter personal violence predicted being a case of mental illness (OR = 3.400; 95%CI = 1.374 - 8.414 and OR = 5.676; 95%CI = 1.251 - 25.757 respectively). CONCLUSIONS: Rates of mental disorder found in our study were lower than those previously observed internationally and in Africa, perhaps reflecting stigma about disclosing symptoms. The predictive nature of violence on mental disorder is in keeping with international evidence. Our study demonstrated that exposure to inter personal violence within the last 12 months and increasing numbers of female children predict the presence of mental illness in a sample of pregnant Nigerian women. Training and education for primary health care and obstetric health workers should highlight these areas. PMID- 22054305 TI - Antioxidant and hepatoprotective effects of ethanol extract of Vitex glabrata on carbon tetrachloride-induced liver damage in rats. AB - This study was aimed at evaluating the antioxidant and hepatoprotective effects of the ethanol extract of Vitex glabrata (EEVG) in a CCl(4)-induced liver damage model in rats; and to isolate and characterise the bioactive constituent from EEVG. Hepatoprotective activity was evaluated by changes in the levels of the serum enzymes viz. AST, ALT, ALP and total bilirubin, and further by histopathological examinations of liver tissues. Antioxidant activity was measured in terms of superoxide dismutase, GSH, lipid peroxidation (LPO), catalase and peroxidase levels in liver homogenate. The pentamethoxy flavonoid artemetin was isolated and characterised from EEVG. Artemetin and EEVG pre treatment significantly (p < 0.001) inhibited LPO in CCl(4)-intoxicated livers and reduced the elevated serum levels of AST, ALT, ALP and bilirubin to normal; it also brought back the normal architecture of liver tissues. Antioxidant activity of EEVG was found to be comparable with silymarin (p < 0.05). In conclusion, EEVG possesses significant hepatoprotective activity, which may be mediated by the antioxidant mechanisms of its components, predominantly artemetin. PMID- 22054306 TI - Inequalities in diet and nutrition. AB - The inequality of nutrition and obesity re-focuses concern on who in society is consuming the worst diet. Identification of individuals with the worst of dietary habits permits for targeting interventions to assuage obesity among the population segment where it is most prevalent. We argue that the use of fiscal interventions does not appropriately take into account the economic, social and health circumstances of the intended beneficiaries of the policy. This paper reviews the influence of socio-demographic factors on nutrition and health status and considers the impacts of nutrition policy across the population drawing on methodologies from both public health and welfare economics. The effects of a fat tax on diet are found to be small and while other studies show that fat taxes saves lives, we show that average levels of disease risk do not change much: those consuming particularly bad diets continue to do so. Our results also suggest that the regressivity of the policy increases as the tax becomes focused on products with high saturated fat contents. A fiscally neutral policy that combines the fat tax with a subsidy on fruit and vegetables is actually more regressive because consumption of these foods tends to be concentrated in socially undeserving households. We argue that when inequality is of concern, population-based measures must reflect this and approaches that target vulnerable populations which have a shared propensity to adopt unhealthy behaviours are appropriate. PMID- 22054307 TI - Atrial pace on PVC algorithm inducing ventricular fibrillation. PMID- 22054308 TI - Factors that motivate young pharmacists to work in rural communities in the Ukraine. AB - INTRODUCTION: A number of identified factors can influence clinicians' location of practice decisions; however, little is known about the location decisions of pharmacists. In general, males are more likely to work in rural and remote regions, and students with a rural background are more likely to work in rural communities after graduation. In the Ukraine, pharmaceutical health care is important because a patient's first visit is often to the pharmacy, rather than to a GP. This study sought to understand what motivates Ukraine pharmacy students to practice in rural areas. METHODS: The first part of the study used a quantitative design with questionnaires based on Fuglistaller's model for measuring the motivation of entrepreneurs, because working in a rural Ukraine pharmacy means, in most cases, operating a privately owned pharmacy. The second part was qualitative to verify these results. RESULTS: The students' motivation to work in rural areas after graduation depended on their sex and place of birth, but this was not decisive. More influential were the factors that motivate operating a privately owned pharmacy. Within the group that considered working in a privately owned pharmacy in a rural community, motivation was more intrinsic (eg enjoys helping people), while negative factors were more external (eg financial risk). CONCLUSION: Students from the National University of Pharmacy in Kharkiv comprise the majority of pharmacists in the Ukraine. They are interested in working in a rural area as long as opportunities align with their individual expectations. The two main factors found that would supply more young graduates to rural areas were: (1) improving rural living conditions; and (2) fostering the mental attitude required for operating a private pharmacy. In addition, decreasing related bureaucracy, and increasing financial and fiscal grants may enhance medical and pharmaceutical health care in rural communities of the Ukraine.Key words: graduate pharmacists, living conditions, motivation, privately owned pharmacy, Ukraine. PMID- 22054309 TI - Effect of route of delivery on heterologous protection against HCV induced by an adenovirus vector carrying HCV structural genes. AB - BACKGROUND: An effective vaccine and new therapeutic methods for hepatitis C virus (HCV) are needed, and a potent HCV vaccine must induce robust and sustained cellular-mediated immunity (CMI). Research has indicated that adenoviral and vaccinia vectors may have the ability to elicit strong B and T cell immune responses to target antigens. RESULTS: A recombinant replication-defective adenovirus serotype 5 (rAd5) vector, rAd5-CE1E2, and a recombinant Tian Tan vaccinia vector, rTTV-CE1E2, were constructed to express the HCV CE1E2 gene (1 746 amino acid HCV 1b subtype). Mice were prime-immunised with rAd5-CE1E2 delivered via intramuscular injection (i.m.), intranasal injection (i.n.), or intradermal injection (i.d.) and boosted using a different combination of injection routes. CMI was evaluated via IFN-gamma ELISPOT and ICS 2 weeks after immunisation, or 16 weeks after boost for long-term responses. The humoral response was analysed by ELISA. With the exception of priming by i.n. injection, a robust CMI response against multiple HCV antigens (core, E1, E2) was elicited and remained at a high level for a long period (16 weeks post-vaccination) in mice. However, i.n. priming elicited the highest anti-core antibody levels. Priming with i.d. rAd5-CE1E2 and boosting with i.d. rTTV-CE1E2 carried out simultaneously enhanced CMI and the humoral immune response, compared to the homologous rAd5-CE1E2 immune groups. All regimens demonstrated equivalent cross protective potency in a heterologous surrogate challenge assay based on a recombinant HCV (JFH1, 2a) vaccinia virus. CONCLUSIONS: Our data suggest that a rAd5-CE1E2-based HCV vaccine would be capable of eliciting an effective immune response and cross-protection. These findings have important implications for the development of T cell-based HCV vaccine candidates. PMID- 22054310 TI - Does laparoscopic management of deep infiltrating endometriosis improve quality of life? A prospective study. AB - BACKGROUND: Deep infiltrating endometriosis (DIE) can affect importantly patients' quality of life (QOL). The aim of this study is to evaluate the impact of the laparoscopic management of DIE on QOL after six months from treatment. METHODS: It is a prospective cohort study. In a tertiary care university hospital, between April 2008 and December 2009, 100 patients underwent laparoscopic management of DIE and completed preoperatively and 6-months postoperatively a QOL questionnaire, the short form 36 (SF-36).Quality of life was measured through the SF-36 scores. Intra-operative details of disease site, number of lesions, type of intervention, period of hospital stay and peri operative complications were noted. RESULTS: Six months postoperatively all the women had a significant improvement in every scale of the SF-36 (p < 0,0005). Among patients with intestinal DIE, significant differences in postoperative scores of SF-36 were not detected between patients submitted to nodule shaving and segmental resection (p > 0.05). There was no significant difference in the SF 36 scores at 6 months from surgery between patients who received postoperative medical treatment and patients who did not (p > 0.05). CONCLUSIONS: Laparoscopic excision of DIE lesions significantly improves general health and psycho emotional status at six months from surgery without differences between patients submitted to intestinal segmental resection or intestinal nodule shaving. PMID- 22054312 TI - Cancer and primary care: the clinical and research agenda. PMID- 22054313 TI - From patient advocate to gatekeeper: understanding the effects of the NHS reforms. PMID- 22054314 TI - Musculoskeletal disorders: time for joint action in primary care. PMID- 22054315 TI - Long-term cardiovascular conditions: the role of primary care. PMID- 22054316 TI - Are the serious problems in cancer survival partly rooted in gatekeeper principles? PMID- 22054317 TI - Are the serious problems in cancer survival partly rooted in gatekeeper principles? PMID- 22054318 TI - Are the serious problems in cancer survival partly rooted in gatekeeper principles? PMID- 22054319 TI - Extent of cotton-bud use in ears. PMID- 22054320 TI - Climate change and health: time to adopt environmental probity? PMID- 22054321 TI - Kenneth William Cross: an appreciation. PMID- 22054323 TI - Risk of prostate cancer associated with benign prostate disease: a primary care case-control study. AB - BACKGROUND: Benign diseases of the prostate are common in the general male population, and prostate cancer is the most common cancer in men. Uncertainty as to the nature of the association between benign and malignant disease is a source of concern for patients and clinicians. AIM: To determine the likelihood of men with benign prostate disease developing prostate cancer compared with men without disease. DESIGN: Incident matched case-control study. METHOD: All incident cases of prostate cancer (n = 984) were identified in a nationally representative community-based population, and each was matched by age with two controls with no prostate cancer (n = 1968). Participants' records of the previous 5 years were searched for diagnoses of benign prostate disease. Analyses investigated an a priori hypothesis that clinicians may record disease as benign until proven to be malignant, causing misleading significant associations between benign and malignant diagnoses. RESULTS: There was a significant association between a diagnosis of prostate cancer and a benign diagnosis at any time in the previous 5 years: odds ratio (OR) 1.57 (95% confidence interval [CI] = 1.32 to 1.88). However, there was no significant association when benign diagnoses within 6 months and within 12 months of cancer diagnoses were excluded: OR 1.19 (95% CI = 0.97 to 1.46) and OR 1.00 (95% CI = 0.79 to 1.27) respectively. CONCLUSION: Findings from this study suggest that unless prostate cancer is detected within 6 months, men diagnosed for the first time with benign disease are at no greater risk of prostate cancer than those with no recorded prostate disease. PMID- 22054324 TI - Inventing the wheel in general practice. PMID- 22054325 TI - Education at the edge of chaos. PMID- 22054327 TI - The Olympic legacy. PMID- 22054328 TI - Primary care and international health links: should GPs get more involved? PMID- 22054330 TI - Patients' needs following colorectal cancer diagnosis: where does primary care fit in? AB - BACKGROUND: Colorectal cancer is the third most common cancer in the UK. Patients with colorectal cancer spend most of their time in the community, but the role of primary care in their management and follow-up is unclear. AIM: To explore colorectal cancer patients' experiences of psychosocial problems and their management in primary and specialist care. DESIGN AND SETTING: Longitudinal qualitative study of participants recruited from three hospitals in the west of Scotland and interviewed in their own homes. METHOD: In-depth interviews with 24 participants with a new diagnosis of colorectal cancer, and then follow-up interviews 12 months later. RESULTS: Participants' needs following a diagnosis for colorectal cancer included physical, psychological, and social issues. GPs played a key role in diagnosis, after which they were less involved. Participants valued GPs making unsolicited contact and offering support. Participants described being well supported by clinical nurse specialists who are expert in the illness, and who provide continuity of care and psychological support. A year after diagnosis, when there was less contact with GPs and clinical nurse specialists, participants still faced challenges associated with the ongoing impact of colorectal cancer. CONCLUSION: While some patients enjoyed straightforward recoveries from surgery, others experienced longer-term implications from their disease and treatment, particularly bowel-function issues, fatigue, anxiety, and sexual problems. The potential for primary care to contribute more to the ongoing care of colorectal cancer patients was identified. PMID- 22054331 TI - Spirometry in primary care for case finding and management of chronic obstructive pulmonary disease primary care diagnostic technology update. PMID- 22054332 TI - Tips for GP trainees working in palliative care. PMID- 22054333 TI - Urgent suspected cancer referrals from general practice: audit of compliance with guidelines and referral outcomes. AB - BACKGROUND: Late diagnosis contributes to the UK having poorer cancer survival than many countries in Europe. Cancer referral guidelines help GPs decide which patients to refer urgently for further investigation. AIM: To examine primary care referral patterns, compliance with referral guidance, and eventual outcome for patients. DESIGN AND SETTING: Prospective audit within general practice in Scotland. METHOD: GPs in Scotland reviewed all urgent suspected cancer referrals over a 6-month period. They noted the final diagnosis and assessed whether the referral was in accordance with agreed referral guidelines. RESULTS: A total of 18 775 urgent suspected cancer referrals were analysed from 516 GP practices. The referral rate ranged from 3.7 to 24.0 per 1000 per annum; 30.8% of referrals were for patients aged under 50 years, yet this age group accounts for only 11.1% of all diagnosed cancers; 10.3% of all urgent cancer referrals were for suspected melanoma, despite this cancer accounting for only 4.1% of new cancers. The proportion of patients subsequently diagnosed with cancer was greatest for leukaemia (61.7%), prostate (52.6%), and lung cancer referrals (39.7%), and lowest for melanoma (11.8%), oesophago-gastric (11.2%), brain (10.6%), and laryngeal cancer referrals (7.8%). Compliance with referral guidelines was 90.9%. A large proportion of referrals considered to be outside the guidelines still had a cancer diagnosed (urological 15.9%, lung 8.8%, colorectal 8.4%, and breast 6.4%). CONCLUSION: There is wide variation in GP referral rates for suspected cancer with a greater than expected proportion of referrals for younger people. Many referrals considered to be outside the national guidelines were diagnosed with cancer, suggesting factors other than those in referral guidelines alert GPs to the possibility of cancer. PMID- 22054334 TI - Identifying patients with suspected gastro-oesophageal cancer in primary care: derivation and validation of an algorithm. AB - BACKGROUND: Gastro-oesphageal is one of the most common cancers worldwide. Evidence suggested that increased awareness of symptoms and earlier diagnosis could help improve treatment options and improve survival. AIM: To derive and validate an algorithm to estimate the absolute risk of having gastro-oesophageal cancer in patients in primary care with and without symptoms. DESIGN AND SETTING: Cohort study of 375 UK QResearch(r) general practices for development, and 189 for validation. METHOD: Included patients were aged 30-84 years, free at baseline of a diagnosis of gastro-oesophageal cancer, and without dysphagia, haematemesis, abdominal pain, appetite loss, or weight loss recorded in previous 12 months. The primary outcome was incident diagnosis of gastro-oesophageal cancer recorded in the next 2 years. Risk factors examined were age, body mass index, alcohol status, smoking status, deprivation, family history of gastrointestinal cancer, dysphagia, previous diagnosis of cancer apart from gastro-oesophageal cancer, haematemesis, abdominal pain, appetite loss, weight loss, tiredness, and anaemia. Cox proportional hazards models were used to develop risk equations. Measures of calibration and discrimination assessed performance in the validation cohort. RESULTS: There were 2527 incident cases of gastro-oesophageal cancer from 4.1 million person-years in the derivation cohort. Independent predictors were age, smoking, dysphagia, haematemesis, abdominal pain, appetite loss, weight loss, and anaemia. On validation, the algorithms explained 71% of the variation in females and 73% in males. The receiver operating curve statistics were 0.89 (females) and 0.92 (males). The D statistic was 3.2 (females) and 3.3 (males). The 10% of patients with the highest predicted risks included 77% of all gastro-oesophageal cancers diagnosed over the next 2 years. CONCLUSION: The algorithm has good performance and could potentially be used to help identify those at highest risk of gastro-oesophageal cancer, to facilitate early referral and investigation. PMID- 22054335 TI - Identifying patients with suspected lung cancer in primary care: derivation and validation of an algorithm. AB - BACKGROUND: Lung cancer has one of the lowest survival outcomes of any cancer because more then two-thirds of patients are diagnosed when curative treatment is not possible. The challenge is to help earlier diagnosis of lung cancer and hence improve prognosis. AIM: To derive and validate an algorithm incorporating information on symptoms, to estimate the absolute risk of having lung cancer DESIGN AND SETTING: Cohort study of 375 UK QResearch(r) general practices for development, and 189 for validation. METHOD: Selected patients were aged 30-84 years and free of lung cancer at baseline and haemoptysis, loss of appetite, or weight loss in previous 12 months. Primary outcome was incident diagnosis of lung cancer recorded in the next 2 years. Risk factors examined were: haemoptysis, appetite loss, weight loss, cough, dyspnoea, tiredness, hoarseness, smoking, body mass index, deprivation score, family history of lung cancer, other cancers, asthma, chronic obstructive airways disease, pneumonia, asbestos exposure, and anaemia. Cox proportional hazards models with age as the underlying time variable were used to develop separate risk equations in males and females. Measures of calibration and discrimination assessed performance in the validation cohort. RESULTS: There were 3785 incident cases of lung cancer arising from 4 289 282 person-years in the derivation cohort. Independent predictors were haemoptysis, appetite loss, weight loss, cough, body mass index, deprivation score, smoking status, chronic obstructive airways disease, anaemia, and prior cancer (females only). On validation, the algorithms explained 72% of the variation. The receiver operating characteristic (ROC) statistics were 0.92 for both females and males. The D statistic was 3.25 for females and 3.29 for males. The 10% of patients with the highest predicted risks included 77% of all lung cancers diagnosed over the subsequent 2 years. CONCLUSION: The algorithm has good discrimination and calibration and could potentially be used to identify those at highest risk of lung cancer, to facilitate early referral and investigation. PMID- 22054336 TI - Enhancing ventilation in homes of children with asthma: pragmatic randomised controlled trial. AB - BACKGROUND: Few robust studies have tested whether enhancing housing also improves health. AIM: To evaluate the effectiveness of installing ventilation systems, and central heating where necessary, in the homes of children with moderate or severe asthma. DESIGN AND SETTING: Pragmatic randomised controlled trial (RCT) in homes within Wrexham County Borough, Wales, UK. METHOD: A pragmatic RCT was carried out, of a tailored package of housing improvements providing adequate ventilation and temperature, following inspection by a housing officer. One hundred and ninety-two children with asthma aged 5 to 14 years, identified from general practice registers, were randomised to receive this package, either immediately or a year after recruitment. At baseline, and after 4 and 12 months, parents reported their child's asthma-specific and generic quality of life, and days off school. RESULTS: The package improved parent-reported asthma-specific quality of life significantly at both 4 and 12 months. At 12 months, this showed an adjusted mean difference between groups of 7.1 points (95% confidence interval [CI] = 2.8 to 11.4, P= 0.001): a moderate standardised effect size of 0.42. The generic quality-of-life scale showed reported physical problems were significantly reduced at 4 months, but not quite at 12 months, when the mean difference was 4.5 (95% CI = -0.2 to 9.1, P= 0.061). The improvement in psychosocial quality of life at 12 months was not significant, with a mean difference of 2.2 (95% CI = -1.9 to 6.4, P= 0.292). Parent-reported school attendance improved, but not significantly. CONCLUSION: This novel and pragmatic trial, with integrated economic evaluation, found that tailored improvement of the housing of children with moderate to severe asthma significantly increases parent-reported asthma-related quality of life and reduces physical problems. Collaborative housing initiatives have potential to improve health. PMID- 22054337 TI - Enhancing ventilation in homes of children with asthma: cost-effectiveness study alongside randomised controlled trial. AB - BACKGROUND: There has been little rigorous economic analysis of the relationship between asthma and improved housing. AIM: To evaluate the cost-effectiveness of installing ventilation systems, and central heating if necessary, in homes of children with 'moderate' or 'severe' asthma. DESIGN AND SETTING: An incremental cost-effectiveness analysis alongside a pragmatic randomised controlled trial of a tailored package of housing modifications designed to improve ventilation and household heating in homes within Wrexham County Borough, Wales, UK. METHOD: A total of 177 children aged between 5 and 14 years, identified from general practice registers, were studied. Parents reported on the quality of life of their children over a 12-month period. General practices reported on health service resources used by those children, and their asthma-related prescriptions, over the same period. RESULTS: The tailored package shifted 17% of children in the intervention group from 'severe' to 'moderate' asthma, compared with a 3% shift in the control group. The mean cost of these modifications was L1718 per child treated or L12300 per child shifted from 'severe' to 'moderate'. Healthcare costs over 12 months following randomisation did not differ significantly between intervention and control groups. Bootstrapping gave an incremental cost effectiveness ratio (ICER) of L234 per point improvement on the 100-point PedsQLTM asthma-specific scale, with 95% confidence interval (CI) = L140 to L590. The ICER fell to L165 (95% CI = L84 to L424) for children with 'severe' asthma. CONCLUSION: This novel and pragmatic trial, with integrated economic evaluation, reported that tailored improvement of the housing of children with moderate to severe asthma is likely to be a cost-effective use of public resources. This is a rare example of evidence for collaboration between local government and the NHS. PMID- 22054338 TI - Risk of pneumonia in patients taking statins: population-based nested case control study. AB - BACKGROUND: Community-acquired pneumonia is one of the most common causes of hospitalisation and death in older people. Recent research suggests that statins might improve the outcome of infectious diseases because of their anti-oxidative and anti-inflammatory properties. AIM: To estimate the association between current statin use and the risk of community-acquired pneumonia. DESIGN AND SETTING: Nested case-control study of 443 general practices in the UK within the QResearch(r) database. METHOD: Individuals with newly recorded pneumonia, diagnosed between 1996 and 2006 and aged 45 years and older, were matched with up to five controls by age, sex, general practice, and calendaryear Odds ratios for pneumonia associated with statin use were adjusted for smoking status, deprivation, comorbidities, use of acid-lowering drugs, influenza, and pneumococcal vaccines. RESULTS: The analysis found a decreased risk of pneumonia in patients prescribed statins in the year prior to diagnosis (adjusted odds ratio = 0.78, 95% confidence interval [CI] = 0.74 to 0.83), particularly in patients with prescriptions in the last 28 days (adjusted odds ratio = 0.68, 95% CI = 0.63 to 0.73). Atorvastatin and simvastatin had similar associations with pneumonia risk. Analysis repeated on lobar and pneumococcal pneumonia cases showed comparable results. CONCLUSION: In this large population-based case control study, current exposure to statins was associated with a reduced risk of pneumonia. The findings were similar to other observational population-based studies, but further randomised controlled trials are necessary before recommending statins to patients at high risk of pneumonia. PMID- 22054339 TI - Spirituality in general practice: a qualitative evidence synthesis. AB - BACKGROUND: Although it is now common to see spirituality as an integral part of health care, little is known about how to deal with this topic in daily practice. AIM: To investigate the literature about GPs' views on their role in spiritual care, and about their perceived barriers and facilitating factors in assessing spiritual needs. DESIGN: Qualitative evidence synthesis. METHOD: The primary data sources searched were MEDLINE, Web of Science, CINAHL, Embase, and ATLA Religion Database. Qualitative studies that described the views of GPs on their role in providing spiritual care, or that described the barriers and facilitating factors they experience in doing so, were included. Quantitative studies, descriptive papers, editorials, and opinion papers were excluded. RESULTS: Most GPs see it as their role to identify and assess patients' spiritual needs, despite perceived barriers such as lack of time and specific training. However, they struggle with spiritual language and experience feelings of discomfort and fear that patients will refuse to engage in the discussion. Communicating willingness to engage in spiritual care, using a non-judgemental approach, facilitates spiritual conversations. CONCLUSION: The results of the studies included here were mostly congruent, affirming that many GPs see themselves as supporters of patients' spiritual wellbeing, but lack specific knowledge, skills, and attitudes to perform a spiritual assessment and to provide spiritual care. Spirituality may be of special consequence at the end of life, with an increased search for meaning. Actively addressing spiritual issues fits into the biopsychosocial-spiritual model of care. Further research is needed to clarify the role of the GP as a spiritual care giver. PMID- 22054340 TI - An interview with Medecins Sans Frontieres. PMID- 22054341 TI - Cancer survivorship: the impact on primary care. PMID- 22054342 TI - Lessons from evaluation of the NHS white paper Our Health, Our Care, Our Say. PMID- 22054343 TI - Enzyme immunoassay for tenuazonic acid in apple and tomato products. AB - The Alternaria mycotoxin tenuazonic acid was derivatized with succinic anhydride and conjugated to keyhole limpet hemocyanin (KLH) and to horseradish peroxidase (HRP), respectively. The KLH conjugate was used to produce polyclonal antibodies in rabbits. A competitive direct enzyme immunoassay (EIA) for tenuazonic acid was established, which was moderately sensitive for tenuazonic acid [50% inhibition concentration (IC(50)): 320 +/- 130 ng/mL] but strongly reacted with tenuazonic acid acetate (IC(50): 23.3 +/- 7.5 ng/mL). Therefore, an optimized EIA protocol was established, which employed acetylation of standard and sample extract solutions. The mean standard curve detection limit (IC(30)) for tenuazonic acid acetate was 5.4 +/- 2.0 ng/mL, enabling detection limits for tenuazonic acid in apple and tomato products of 25-50 ng/g (150 ng/g in tomato paste). Recoveries in a concentration range of 50-2000 ng/g were 60-130% in apple juice and tomato juice and 40-150% in other tomato products. Tenuazonic acid was detected in apple juice and tomato products from German retail shops at levels of 50-200 ng/g. In conclusion, this novel EIA for tenuazonic acid could be useful within a screening program for Alternaria mycotoxins in food. PMID- 22054344 TI - Errata. PMID- 22054346 TI - A pilot study to explore the effectiveness of "early" rehabilitation after a hospital admission for chronic heart failure. AB - People with chronic heart failure (CHF) experience acute exacerbations of their symptoms. These episodes are costly to patients and the health service. The study was a single group, pretest and posttest design. Seventeen patients with left ventricular systolic dysfunction (LVSD) started rehabilitation within 4 weeks of hospital discharge. The 6 week rehabilitation programme included exercise and self-management education. The hospital anxiety and depression scale (HADS), the incremental and endurance shuttle walking tests (ISWT/ESWT) were assessed at baseline and after rehabilitation. The number and duration of any CHF admissions in the year before and the year after rehabilitation were also recorded. Improvements in the ISWT, ESWT, and depression were, mean (95% confidence interval [CI]) 60.6 (36.0-85.2) metres, 356.0 (173.0-539.0) seconds (both p<=0.001) and (-)1.0 ((-)1.8-(-)0.2) points (p<0.05), respectively. HADS anxiety improvements failed to reach significance. At 1 year, there was a significant decrease in CHF-related hospitalisations, mean change (95% CI) (-)0.8 ((-)1.1-( )0.4), p<=0.001 and CHF bed days (-)13.0 ((-)24.4-(-)1.6), p<0.05. Early rehabilitation significantly improved exercise capacity and depression and reduced CHF-associated health care utilisation in patients who had recently been hospitalised. The intervention was safe. However, the sample size was small and results were not compared to a control group. Therefore, the effects of natural recovery are unknown. PMID- 22054347 TI - GLP-1, exendin-4 and C-peptide regulate pancreatic islet microcirculation, insulin secretion and glucose tolerance in rats. AB - GLP-1 (glucagon-like peptide 1) and its mimetic exendin-4 are used against Type 2 diabetes. C-peptide has also proven promising to enhance insulin action. Since insulin secretion in vivo can be rapidly tuned by changes in islet microcirculation, we evaluated the influence of GLP-1, exendin-4 and C-peptide on pancreatic IBF (islet blood flow), and dynamic changes in insulin secretion and glycaemia in the rat. Adult male Wistar rats were divided into four groups given intravenous saline, GLP-1, exendin-4 or C-peptide respectively and administered either saline or 30% glucose. Furthermore, we investigated the effect of intravenous infusion of different doses of exendin-4 into either the femoral vein or the portal vein on islet microcirculation. A non-radioactive microsphere technique was adopted to measure the regional blood flow. Both GLP-1 and exendin 4 prevented the glucose-induced PBF (pancreatic blood flow) redistribution into the islets. Infusion of exendin-4 into the portal vein did not alter pancreatic islet microcirculation, while infusion of exendin-4 into femoral vein significantly decreased basal IBF. C-peptide increased basal IBF and the proportion of IBF out of total PBF, but did not affect the islet microcirculation after glucose administration. GLP-1, exendin-4 and C-peptide stimulated insulin secretion and significantly decreased glycaemia. Blocking NO formation did not prevent the decreased IBF and post-load glycaemia evoked by exendin-4, but further decreased IBF and KBF (kidney blood flow) and increased basal glycaemia. Blocking the vagus nerve enhanced pancreatic IBF and further decreased post-load glycaemia and KBF and increased basal glycaemia. The vascular modulatory effect on pancreatic islet microcirculation described herein, with subsequent effects on in vivo insulin secretion and glycaemia, might be one of the mechanisms underlying the anti-diabetic actions of GLP-1 and its long acting mimetic exendin 4, as well as that of C-peptide. PMID- 22054348 TI - In vivo quantitative evaluation of the transport kinetics of gold nanocages in a lymphatic system by noninvasive photoacoustic tomography. AB - Sentinel lymph node (SLN) biopsy has emerged as a preferred method for axillary lymph node staging of breast cancer, and imaging the SLN in three-dimensional space is a prerequisite for the biopsy. Conventional SLN mapping techniques based on the injection of an organic dye or a suspension of radioactive colloids suffer from invasive surgical operation for visual detection of the dye or hazardous radioactive components and low spatial resolution of Geiger counters in detecting the radioactive colloids. This work systematically investigates the use of gold nanocages (AuNCs) as a novel class of optical tracers for noninvasive SLN imaging by photoacoustic (PA) tomography in a rat model. The transport of AuNCs in a lymphatic system and uptake by the SLN were evaluated by PA tomography on the axillary region of a rat. Quantification of AuNCs accumulated in the lymph node was achieved by correlating the data from PA imaging with the results from inductively coupled plasma mass spectrometry. Several parameters were systematically evaluated and optimized, including the concentration, size, and surface charge of the AuNCs. These results are critical to the further development of this AuNC-based PA tomography system for noninvasive SLN imaging, providing valuable information for metastatic cancer staging. PMID- 22054349 TI - Pure laparoscopic distal pancreatectomy with en bloc celiac axis resection. AB - BACKGROUND: Recent technological developments and improved endoscopic procedures have greatly enlarged the applications of laparoscopic pancreatic resection. PATIENT AND METHODS: A 77-year-old female with invasive ductal cancer of the pancreatic body touching the common hepatic and splenic arteries underwent a pure laparoscopic distal pancreatectomy with en bloc celiac axis resection (DP-CAR). The celiac axis, the celiac plexus and ganglions, the left gastric artery, the Gerota fascia, the left adrenal gland, and the retroperitoneal fat tissues above the left renal vein were removed en bloc. RESULTS: The procedure took 245 minutes and there was minimal blood loss. The postoperative course was uneventful and the patient was discharged on the seventh postoperative day. The surgical margins were histologically clear (R0 resection). CONCLUSION: Pure laparoscopic DP-CAR is minimally invasive, safe and feasible, and can achieve R0 resection in selected patients with pancreatic invasive ductal adenocarcinoma. PMID- 22054350 TI - Quantitative matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis of synthetic polymers and peptides. AB - Matrix-assisted laser desorption ionization (MALDI) is a very powerful and widely used mass spectrometric technique to ionize high molecular weight compounds. The most commonly used dried droplet (DD) technique can lead to a concentration distribution of the analyte on the target and is therefore often not suitable for reproducible analyses. We developed a new solvent-free deposition technique, called compressed sample (CS), to prevent the distribution of the analytes caused by the crystallization of the compounds. The CS technique presented in this work allows the quantitative analysis of synthetic polymers such as derivatized maltosides with correlation coefficients of 0.999 and peptides up to 3500 Da with correlation coefficients of at least 0.982 without the use of stable-isotope labeled standards. PMID- 22054353 TI - Instructions to Contributors. PMID- 22054351 TI - Commentary. PMID- 22054354 TI - Operative Dentistry Home Page. PMID- 22054355 TI - Photosensitized oxidation of emerging organic pollutants by tetrakis C60 aminofullerene-derivatized silica under visible light irradiation. AB - We recently reported that C(60) aminofullerenes immobilized on silica support (aminoC(60)/silica) efficiently produce singlet oxygen ((1)O(2)) and inactivate virus and bacteria under visible light irradiation. (1) We herein evaluate this new photocatalyst for oxidative degradation of 11 emerging organic contaminants, including pharmaceuticals such as acetaminophen, carbamazepine, cimetidine, propranolol, ranitidine, sulfisoxazole, and trimethoprim, and endocrine disruptors such as bisphenol A and pentachlorophenol. Tetrakis aminoC(60)/silica degraded pharmaceuticals under visible light irradiation faster than common semiconductor photocatalysts such as platinized WO(3) and carbon-doped TiO(2). Furthermore, aminoC(60)/silica exhibited high target-specificity without significant interference by natural organic matter. AminoC(60)/silica was more efficient than unsupported (water-suspended) C(60) aminofullerene. This was attributed to kinetically enhanced (1)O(2) production after immobilization, which reduces agglomeration of the photocatalyst, and to adsorption of pharmaceuticals onto the silica support, which increases exposure to (1)O(2) near photocatalytic sites. Removal efficiency increased with pH for contaminants with a phenolic moiety, such as bisphenol A and acetaminophen, because the electron-rich phenolates that form at alkaline pH are more vulnerable to singlet oxygenation. PMID- 22054356 TI - Expedited batch processing and analysis of transposon insertions. AB - BACKGROUND: With advances in sequencing technology, greater and greater amounts of eukaryotic genome data are becoming available. Often, large portions of these genomes consist of transposable elements, frequently accounting for 50% or more in vertebrates. Each transposable element family may have thousands or tens of thousands of individual copies within a given genome, and therefore it can take an exorbitant amount of time and effort to process data in a meaningful fashion. FINDINGS: In order to combat this problem, we developed a set of bioinformatics techniques and programs to streamline the analysis. This includes a unique Perl script which automates the process of taking BLAST, Repeatmasker and similar data to extract and manipulate the hit sequences from the genome. This script, called Process_hits uses an object-oriented methodology to compile all hit locations from a given file for processing, organize this data into useable categories, and output it in multiple formats. CONCLUSIONS: The program proved capable of handling large amounts of transposon data in an efficient fashion. It is equipped with a number of useful sub-functions, each of which is contained within its own sub-module to allow for greater expandability and as a foundation for future program design. PMID- 22054357 TI - Toxoplasma gondii infection in pregnant women in China. AB - Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii, is one of the most common parasitic infections in humans. Primary infection in pregnant women can be transmitted to the fetus leading to miscarriage or congenital toxoplasmosis. Carefully designed nationwide seroprevalence surveys and case control studies of risk factors conducted primarily in Europe and America, have shaped our view of the global status of maternal and congenital infection, directing approaches to disease prevention. However, despite encompassing 1 in 5 of the world's population, information is limited on the status of toxoplasmosis in China, partly due to the linguistic inaccessibility of the Chinese literature to the global scientific community. By selection and analysis of studies and data, reported within the last 2 decades in China, this review summarizes and renders accessible a large body of Chinese and other literature and aims to estimate the seroprevalence in Chinese pregnant women. It also reviews the prevalence trends, risk factors, and clinical manifestations. The key findings are (1) the majority of studies show that the overall seroprevalence in Chinese pregnant women is less than 10%, considerably lower than a recently published global analysis; and (2) the few available appropriate studies on maternal acute infection suggested an incidence of 0.3% which is broadly comparable to studies from other countries. PMID- 22054358 TI - SIU scholarship: Dr. Terkaa Atim. PMID- 22054359 TI - Editorial comment. PMID- 22054361 TI - Factors influencing residents' pursuit of urology fellowships. AB - OBJECTIVE: To assess the predictors of residents' pursuit of fellowship training by surveying current urology residents and recent graduates. Postgraduate fellowship training of urologists could be an important source of urologic physician-scientists and continued innovation in urologic care. METHODS: A Web based survey was electronically mailed to urology residents and recent graduates of urologic residency. Variables concerning sex, marital status, debt load, research and clinical exposure, publications, and postgraduate careers were recorded. RESULTS: Of the 71 respondents, 46 (65%) were married and 45% had children/dependents. Of the 69% who applied for fellowship, the "most important" factors influencing the pursuit of fellowship were intellectual appeal (82%), mentors (79%), the desire for an additional point of view for surgical training (58%), and the desire to pursue a career in academics (52%). Forty of those completing a fellowship (87%) versus two of those completing residency alone (13%) would pursue a career in academics. Residents with a mentor were 20 times more likely to pursue a urology fellowship. A shorter residency (5 years), encouragement by a program director, and manuscript publication during residency were also independent predictors. CONCLUSION: Mentorship, a shorter residency, and manuscript publication during residency were independent predictors of pursuing fellowship training. Debt load, age, marital status, and a desire to pursue a career in academic medicine were not significant factors. PMID- 22054362 TI - Editorial comment. PMID- 22054364 TI - Genital piercings: diagnostic and therapeutic implications for urologists. AB - OBJECTIVE: To provide quantitative and qualitative data that will assist evidence based decision making for men and women with genital piercings (GP) when they present to urologists in ambulatory clinics or office settings. Currently many persons with GP seek nonmedical advice. MATERIALS AND METHODS: A comprehensive 35 year (1975-2010) longitudinal electronic literature search (MEDLINE, EMBASE, CINAHL, OVID) was conducted for all relevant articles discussing GP. RESULTS: Authors of general body art literature tended to project many GP complications with potential statements of concern, drawing in overall piercings problems; then the information was further replicated. Few studies regarding GP clinical implications were located and more GP assumptions were noted. Only 17 cases, over 17 years, describe specific complications in the peer-reviewed literature, mainly from international sources (75%), and mostly with "Prince Albert" piercings (65%). Three cross-sectional studies provided further self-reported data. CONCLUSION: Persons with GP still remain a hidden variable so no baseline figures assess the overall GP picture, but this review did gather more evidence about GP wearers and should stimulate further research, rather than collectively projecting general body piercing information onto those with GP. With an increase in GP, urologists need to know the specific differences, medical implications, significant short- and long-term health risks, and patients concerns to treat and counsel patients in a culturally sensitive manner. Targeted educational strategies should be developed. Considering the amount of body modification, including GP, better legislation for public safety is overdue. PMID- 22054365 TI - Editorial comment. PMID- 22054367 TI - Editorial comment. PMID- 22054370 TI - Editorial comment. PMID- 22054371 TI - Efficacy and preoperative prognostic factors of autologous fascia rectus sling for treatment of female stress urinary incontinence. AB - OBJECTIVE: To evaluate the efficacy of the autologous fascia rectus sling in treating female stress urinary incontinence. METHODS: A total of 264 patients treated during a 3-year period for SUI using the autologous fascia rectus sling were retrospectively reviewed. Efficacy was evaluated by the number of pads used daily. Patient satisfaction and correlations between the preoperative parameters and outcome were assessed. RESULTS: The mean follow-up time was 27.8 months. Of the 264 patients, 224 (85%) were successfully treated and satisfied with the outcome of the operation. Of the 224 patients, 200 (75.8%) were totally dry and 24 (9.1%) had improved markedly. The complication rate was 29.2%, with postoperative urgency the most common problem (49 of 264, 18.5%). None of the preoperative parameters were associated with the final outcome. CONCLUSION: The free autologous rectus fascia sling is a highly effective technique for the treatment of female stress incontinence with mild morbidity. PMID- 22054372 TI - Editorial comment. PMID- 22054374 TI - Editorial comment. PMID- 22054375 TI - Editorial comment. PMID- 22054376 TI - Editorial comment. PMID- 22054378 TI - Utility of the R.E.N.A.L. nephrometry scoring system in objectifying treatment decision-making of the enhancing renal mass. AB - OBJECTIVE: To evaluate the treatment patterns of solid renal masses according to the quantifiable anatomic features using nephrometry. The treatment of localized renal cell carcinoma remains overly subjective. The R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines) nephrometry score quantifies the salient characteristics of renal mass anatomy in an objective and reproducible manner. METHODS: Nephrometry scores were available in 615 patients in our prospective kidney tumor database (2000-2010). The nephrometry score sum and its individual component scores were analyzed to determine their relationship to treatment approach. RESULTS: The median age, age adjusted Charlson co-morbidity index, and estimated glomerular filtration rate was 60 years (range 25-89), 2 (range 0-10), and 80.5 mL/min (range 5.1-120.0), respectively. Increasing tumor complexity, as measured by a greater overall nephrometry score was associated with both radical nephrectomy and open partial nephrectomy (P < .0001). Compared with patients who underwent partial nephrectomy, the patients treated with radical nephrectomy had a significantly greater size (R), central proximity (N), and location (L) component scores (P < .001). Furthermore, tumors treated with radical nephrectomy were more often hilar (P < .001). Similarly, compared with minimally invasive partial nephrectomy (laparoscopic or robotic), open partial nephrectomy was associated with an increasing individual component score for size, endophytic, and central proximity to the collecting system (P < .001) and nonpolar location (P = .016). CONCLUSION: The R.E.N.A.L nephrometry score standardizes the reporting of solid renal masses and appears to effectively stratify by treatment type. Although only 1 part of the treatment decision-making process, nephrometry aids in objectifying previously subjective measures. PMID- 22054380 TI - Editorial comment. PMID- 22054381 TI - Editorial comment. PMID- 22054382 TI - Using a saturation biopsy scheme increases cancer detection during repeat biopsy in men with high-grade prostatic intra-epithelial neoplasia. AB - OBJECTIVE: To determine the role of transrectal saturation biopsy for cancer detection in men with high-grade prostatic intra-epithelial neoplasia (HGPIN) diagnosed by extended biopsy. HGPIN was clearly associated with cancer risk in the sextant biopsy era, but this has not been clearly demonstrated in the extended biopsy era. MATERIALS AND METHODS: From 1999 to 2009, 314 men had at least 1 or more repeat biopsy due to the presence of exclusive HGPIN (without any other pathologic finding) in a previous extended biopsy. They were divided into 2 groups according to the initial follow-up biopsy scheme, 178 men were followed up using a second standard extended biopsy scheme and 136 were followed up using the saturation biopsy scheme. RESULTS: In the standard repeat biopsy group, 35 of 178 (19.7%) men had cancer on initial repeat biopsy. In the saturation biopsy group, 42 of 136 (30.9%) had cancer on initial repeat biopsy (overall, P = .04). Multivariate analysis demonstrates that the biopsy scheme on repeat biopsy is an independent predictor of prostate cancer detection (OR 1.85, (95% CI; 1.03, 3.29), exclusive of age, PSA, days from initial biopsy, DRE status and multifocal PIN. Furthermore, there appears to be no further increase in Gleason 6 disease with usage of saturation biopsy in this unique population. CONCLUSION: Cancer detection in men with HGPIN in the contemporary extended biopsy era is substantially improved using saturation technique. PMID- 22054383 TI - Editorial comment. PMID- 22054385 TI - Organ-sparing surgery for penile cancer: complications and outcomes. AB - OBJECTIVE: To evaluate the complications and outcomes of organ-sparing surgery in penile cancer. METHODS: Thirty-two penile cancer patients had undergone organ sparing surgery between 2006 and 2010 in Fudan University Shanghai Cancer Center. Applied surgical techniques included radical circumcision and/or wide local excision. Intraoperative frozen section analyses of circumference and deep margins were performed to guarantee complete removal of cancerous tissue. Complications and oncological and functional outcomes were recorded prospectively. Bilateral inguinal lymphadenectomy was routinely performed in patients with invasive penile cancer. RESULTS: Of 32 patients, 8 underwent radical circumcision, 18 were treated with wide local excision, and 6 received wide local excision and circumcision. Postoperatively, only 3 (9.4%) patients had minor complications. With a median follow-up of 26.5 months, local control was achieved in 29 (90.6%) patients, and 3 patients (9.4%) with positive lymph nodes died of disseminated disease. Of 29 patients who completed follow-up surveys of functional outcome, only 1 (4.5%) claimed decreased sexual function and all reported satisfied urination. CONCLUSION: Organ-sparing surgery, such as radical circumcision and wide local excision is an appropriate treatment option for selected penile cancer patients. It preserves sexual and urination function without significantly increasing the risk of recurrence. PMID- 22054386 TI - Salvage therapy with oral metronomic cyclophosphamide and methotrexate for castration-refractory metastatic adenocarcinoma of the prostate resistant to docetaxel. AB - OBJECTIVE: To investigate the activity and toxicity of metronomic chemotherapy with low-dose oral cyclophosphamide (CTX) and methotrexate (MTX) in patients with metastatic CRPC that progresses after docetaxel. Patients with castration resistant prostate cancer (CRPC) that progresses after docetaxel may benefit from receiving further chemotherapy. METHODS: Patients were treated with CTX 50 mg/d p.o. plus MTX 2.4 mg p.o. twice per week without rest periods. All patients received simultaneous luteinizing hormone-releasing hormone analogue. Prostate specific antigen (PSA) response was defined as a 50% reduction on 2 evaluations at least 4 weeks apart. Objective response was measured according to the RECIST criteria. Pain relief was analyzed with the McGill-Melzack Pain Questionnaire. Simon's 2-stage design for phase II study was used. Time to progression and progression-free and overall survival were computed. Toxicity was recorded according to the CTC-NCCN criteria. RESULTS: A PSA decrease >=50% was recorded in 15 of 58 evaluable patients (25%), and objective partial response in 3 (18%) and stable disease in 4 (24%) of 17 patients with measurable disease. Disease in 10 patients (59%) progressed. Pain intensity decreased in 16 (30%), increased in 18 (33%), and remained stable in 18 (33%) patients. Five patients discontinued narcotic analgesics for a mean duration of 12 weeks. Transitory grade 3 leukopenia was observed in 4 cases (7%), grade 3 thrombocytopenia in 2 (3%), and grade 2 anemia in 4 (7%). CONCLUSION: This study demonstrates the feasibility, activity, and tolerability of oral low-dose CTX and MTX given on a metronomic schedule in patients with CRPC progressing after docetaxel-based chemotherapy. PMID- 22054387 TI - Prognostic impact of C-reactive protein for determining overall survival of patients with castration-resistant prostate cancer treated with docetaxel. AB - OBJECTIVE: To verify the prognostic impact of C-reactive protein (CRP) for patients with castration-resistant prostate cancer (CRPC) treated with docetaxel in a single institution. METHODS: A group of 80 consecutive patients with CRPC were treated with docetaxel in our institution from January 2005 to May 2010. The patients received 75 mg/m(2) of docetaxel intravenously every 3 weeks. The prognostic value of all covariables, including CRP, was assessed using the Cox proportional hazard model. Risk stratification for overall survival was described from the results of the multivariable analysis. RESULTS: The median survival period for all patients was 14.5 months. The multivariable analysis showed that CRP and hemoglobin levels were independent prognostic factors for overall survival. Based on the presence of an elevated CRP concentration and/or a low hemoglobin level, all patients were stratified into 3 risk groups: those with no risk factors (low-risk group), those with 1 risk factor (intermediate-risk group), and those with 2 risk factors (high-risk group). The overall survival curves were clearly tiered according to the risk groups, with the 1-year overall survival rates being 86.3%, 60.5%, and 23.0% for the low-, intermediate-, and high-risk groups, respectively (P <.001). CONCLUSION: CRP is an independent prognostic factor for overall survival of patients with CRPC treated with docetaxel. Risk stratification based on CRP and hemoglobin could be helpful for estimating the overall survival. PMID- 22054388 TI - Self-reported spousal support modifies the negative impact of pain on disability in men with chronic prostatitis/chronic pelvic pain syndrome. AB - OBJECTIVES: To examine changes in the association between pain and patient quality of life (QoL), depressive symptoms, and disability in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) at varying levels of spouse responses to pain. MATERIAL AND METHODS: One-hundred eighty-eight men with CP/CPPS completed a questionnaire, including demographic information. The outcome variables were mental QoL (SF-12 MCS), physical QoL (SF-12 PCS), depressive symptoms (Center for Epidemiological Studies Depression Scale), and disability (Pain Disability Index). Patients also reported on the types of responses they had from their spouses (Multidimensional Pain Inventory), and pain (Short-Form McGill Pain Questionnaire). RESULTS: The association between pain and disability was stronger at higher levels of solicitous responses (eg, "Does some of my chores") (beta = 0.66, P <.05) than it was at moderate (beta = 0.44, P <.05) and lower (beta = 0.23, ns) levels. In contrast, the association between pain and disability was stronger at lower levels (beta = 0.64, P <.05) of distracting responses (eg, "Tries to get me involved in some activity") than it was at moderate (beta = 0.44, P <.05) and higher (beta = 0.25, P <.05) levels. CONCLUSIONS: Solicitous responses to pain increased the negative impact of pain on disability, whereas distracting responses to pain decreased the negative impact of pain on disability in men with CP/CPPS. Solicitous responses may be a reaction to patient pain and associated disability, or may help create or maintain the patient's pain and disability. In either case, distracting rather than solicitous responses to patient pain are to be encouraged in symptom management. PMID- 22054389 TI - Editorial comment. PMID- 22054390 TI - Influence of environmental factors on prevalence, symptoms, and pathologic process of chronic prostatitis/chronic pelvic pain syndrome in northwest China. AB - OBJECTIVES: To compare the prevalence, symptoms, and pathologic changes related to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with significant prostatitis-like symptoms between 2 altitude areas in northwest China. METHODS: From October 2009 to March 2010 community male residents at 3000 m (Delingha) and 400 m (Xi'An) constituted the population base for the present cross-sectional study. All participants completed a detailed questionnaire containing the National Institutes of Health Chronic Prostatitis Symptom Index, and the subjects who met our definition were invited to undergo clinical evaluation. After screening, the subjects considered to have CP/CPPS were separated into 2 groups: those with type IIIa and those with type IIIb CP/CPPS. RESULTS: The prevalence of CP/CPPS with significant prostatitis-like symptoms was significantly different between the 2 groups. Moreover, the National Institutes of Health Chronic Prostatitis Symptom Index of patients with type IIIa and IIIb in 2 groups differed significantly, indicating the aggravation of symptoms of CP/CPPS at a high altitude. Additional investigations showed that reactive oxygen species were increased, accompanied by a decrease in the total antioxidant capacity in the expressed prostatic secretions of patients with type IIIa at a higher altitude. In addition, the tumor necrosis factor-alpha, interleukin-8, and interleukin-10 levels in the expressed prostatic secretions of patients with type IIIa in Delingha were increased compared with that in the patients with type IIIa in Xi'An. Notably, the interleukin-6 level in the expressed prostatic secretions was greater in those with type IIIa and IIIb at a higher altitude than in those with type IIIa and IIIb at a low altitude. CONCLUSIONS: At a high altitude, the symptoms of CP/CPPS were aggravated. Oxidative stress and cytokines might involve in the pathologic process and the aggravation of symptoms. In addition, in a high altitude area the pathomechanisms of type IIIa and IIIb CP/CPPS differed. PMID- 22054391 TI - Editorial comment. PMID- 22054393 TI - Editorial comment. PMID- 22054394 TI - Maternal risk factors for congenital urinary anomalies: results of a population based case-control study. AB - OBJECTIVE: Epidemiologic data addressing maternal risk factors for congenital urinary tract anomalies (CUTA) are limited, with conflicting results for preexisting diabetes mellitus, gestational diabetes, and tobacco and alcohol use. The purpose of this study was to examine the association between maternal risk factors and CUTA in a population-based case-control study. METHODS: A case control analysis was performed using linked birth-hospital discharge records from Washington state for 1987-2007 to evaluate the association between maternal risk factors and CUTA. Cases were children with International Classification of Diseases, Ninth Revision, Clinical Modification codes for urinary anomalies. Controls without urinary tract anomalies were selected from Washington State birth records and matched by birth year in a ratio of 4:1. Logistic regression was performed to evaluate the association between maternal factors and CUTA. RESULTS: A total of 4673 cases and 18,692 controls were studied. In the multivariate analysis, gestational diabetes (OR 1.42, 95% CI 1.09-1.85), preexisting diabetes (OR 3.46, 95% CI 2.17-5.54), and maternal renal disease (OR 5.31, 95% CI 2.40-11.72) were all associated with an increased risk of kidney anomalies. Advanced maternal age (OR 1.20, 95% CI 1.06-1.35), gestational diabetes (OR 1.25, 95% CI 1.01-1.56), maternal renal disease (OR 4.06, 95% CI 1.95-8.46), and non-Caucasian race (OR 0.82, 95% CI .74-.91) were all associated with the risk of ureter, bladder, and urethra anomalies in multivariate analysis. CONCLUSION: Several maternal factors are associated with the risk of CUTA, including diabetes mellitus and maternal renal disease. This information can be used for prenatal counseling and management of women with these risk factors. PMID- 22054395 TI - Editorial comment. PMID- 22054397 TI - Re: Seibold et al.: Urethral ultrasound as a screening tool for stricture recurrence after oral mucosa graft urethroplasty (Urology 2011;78:696-700). PMID- 22054398 TI - Re: Gurocak et al.: Inflammation and oxidative stress in testicular torsion: do they deserve intensive treatment to save both guilty and innocent testes? (Urology 2011;78:164-169). PMID- 22054400 TI - Diversification of CYCLOIDEA-like genes in Dipsacaceae (Dipsacales): implications for the evolution of capitulum inflorescences. AB - BACKGROUND: CYCLOIDEA (CYC)-like genes have been implicated in the development of capitulum inflorescences (i.e. flowering heads) in Asteraceae, where many small flowers (florets) are packed tightly into an inflorescence that resembles a single flower. Several rounds of duplication of CYC-like genes have occurred in Asteraceae, and this is hypothesized to be correlated with the evolution of the capitulum, which in turn has been implicated in the evolutionary success of the group. We investigated the evolution of CYC-like genes in Dipsacaceae (Dipsacales), a plant clade in which capitulum inflorescences originated independently of Asteraceae. Two main inflorescence types are present in Dipsacaceae: (1) radiate species contain two kinds of floret within the flowering head (disk and ray), and (2) discoid species contain only disk florets. To test whether a dynamic pattern of gene duplication, similar to that documented in Asteraceae, is present in Dipsacaceae, and whether these patterns are correlated with different inflorescence types, we inferred a CYC-like gene phylogeny for Dipsacaceae based on representative species from the major lineages. RESULTS: We recovered within Dipsacaceae the three major forms of CYC-like genes that have been found in most core eudicots, and identified several additional duplications within each of these clades. We found that the number of CYC-like genes in Dipsacaceae is similar to that reported for members of Asteraceae and that the same gene lineages (CYC1-like and CYC2B-like genes) have duplicated in a similar fashion independently in both groups. The number of CYC-like genes recovered for radiate versus discoid species differed, with discoid species having fewer copies of CYC1-like and CYC2B-like genes. CONCLUSIONS: CYC-like genes have undergone extensive duplication in Dipsacaceae, with radiate species having more copies than discoid species, suggesting a potential role for these genes in the evolution of disk and ray florets. The similarity in CYC-like gene diversification seen in Dipsacaceae and some members of the Asteraceae sets the stage to investigate whether the convergent evolution of capitulum inflorescences in both groups may have been underlain by convergent evolution in the same gene family. PMID- 22054401 TI - One-pot Zn/CuI/TFA-catalyzed domino three-component-carbocyclization reaction involving biphenyl-2-carbaldehydes/alkynes/piperidine: allenes-mediated construction of phenanthrenes. AB - A one-pot protocol involving Zn/CuI/TFA-catalyzed domino three-component and subsequent carbocyclization reactions is described. The reaction proceeds via formation of propargyl amines from biphenyl-2-carbaldehydes/terminal alkynes/piperidine followed by the elimination of piperidine and ring closure to furnish phenanthrene derivatives in good yields. The strategy involves C(sp)-H activation-CH functionalization with imine-alkyne activation-1,5 hydride shift beta-elimination of piperidine-allene formation-6pi cycloaddition-isomerization domino sequence. Evidence for the involvement of allenes as an intermediate during carbocyclization is discussed. PMID- 22054403 TI - Non-targeted analyses of animal plasma: betaine and choline represent the nutritional and metabolic status. AB - Simple liquid chromatography-mass spectrometry (LC-MS) was applied to non targeted metabolic analyses to discover new metabolic markers in animal plasma. Principle component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) were used to analyse LC-MS multivariate data. PCA clearly generated two separate clusters for artificially induced diabetic mice and healthy control mice. PLS-DA of time-course changes in plasma metabolites of chicks after feeding generated three clusters (pre- and immediately after feeding, 0.5-3 h after feeding and 4 h after feeding). Two separate clusters were also generated for plasma metabolites of pregnant Angus heifers with differing live-weight change profiles (gaining or losing). The accompanying PLS-DA loading plot detailed the metabolites that contribute the most to the cluster separation. In each case, the same highly hydrophilic metabolite was strongly correlated to the group separation. The metabolite was identified as betaine by LC-MS/MS. This result indicates that betaine and its metabolic precursor, choline, may be useful biomarkers to evaluate the nutritional and metabolic status of animals. PMID- 22054404 TI - Re: tissue-engineered autologous urethras for patients who need reconstruction: an observational study. PMID- 22054405 TI - Re: a common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. PMID- 22054406 TI - Words of wisdom. Re: radical nephrectomy and inferior vena cava thrombectomy: outcomes in a lower volume practice. PMID- 22054407 TI - Re: randomised prostate cancer screening trial: 20 year follow-up. PMID- 22054408 TI - Re: radiotherapy and short-term androgen deprivation for localized prostate cancer. PMID- 22054409 TI - Re: early versus late rehabilitation of erectile function after nerve-sparing radical cystoprostatectomy: a prospective randomized study. PMID- 22054410 TI - Sperm GIRK2-containing K+ inward rectifying channels participate in sperm capacitation and fertilization. AB - The GIRK2-containing inward-rectifying K(+) ion channels have been implicated in mammalian spermatogenesis. While the Girk2 null mice are fertile, the male weaver transgenic mice carrying a gain-of-function mutation in the Girk2 gene are infertile. To establish the exact period of spermatogenesis affected by this mutation, we performed StaPut isolation and morphological characterization of the germ cells present in the weaver testis. Germ cells representing all periods of spermatogenesis were identified. However, no spermatozoa were present, suggesting that this mutation only affected the haploid phase of spermatogenesis. Real-time PCR studies performed on StaPut purified germ cells from wild-type mice indicated that the Girk2 transcripts were exclusively expressed in spermatids. Immunofluorescence studies of mouse and boar spermatids/spermatozoa localized the GIRK2 K(+) containing channels to the acrosomal region of the sperm plasma membrane. During porcine in vitro fertilization (IVF), GIRK2-containing channels remained associated with the acrosomal shroud following zona-induced acrosome reaction. Fertilization was blocked by tertiapin-Q (TQ), a specific inhibitor of GIRK channels, and by anti-GIRK2 antibodies. Altogether, studies in two different mammalian species point to a conserved mechanism by which the GIRK2 inward rectifying K(+) ion channels support sperm function during fertilization. PMID- 22054411 TI - Comparison and analysis of fatty acids, sterols, and tocopherols in eight vegetable oils. AB - The similarities and differences of eight vegetable oils produced in China were investigated in terms of their fatty acid, sterol, and tocopherol compositions and subsequent data processing by hierarchical clustering analysis and principal component analysis. The lipid profiles, acquired by analytical techniques tailored to each lipid class, revealed great similarities among the fatty acid profiles of corn and sesame oil as well as few differences in their sterol profiles. It turns out that not only was there great similarity between the fatty acid profiles of corn oil and sesame oil but also there were not too many differences for the sterol profiles. Sunflower and tea-seed oil showed similar sterol compositions, while the tea-seed oil tocopherol was very similar to palm oil. The results demonstrated that the use of only one of these profiles was unreliable for indentifying oil origin and authenticity. In contrast, the use of the sterol or tocopherol profile together with the fatty acid profile more accurately discriminates these oils. PMID- 22054412 TI - Post-irradiation changes of the volatile oil constituents of Monodora myristica (Gaertn) Dunal. AB - Volatile oil rich spices cannot be sterilised by pasteurisation because of the presence of thermal-sensitive components. In this article, we report the effect of irradiation on the volatile constituents of Monodora myristica. The samples were irradiated at ambient conditions at dose levels of 0 and 15 kGy using a linear accelerator at a dose rate of approximately 10(7) Gy s(-1). The volatile oil was extracted via headspace analysis and the quantification carried out with a HP-5MS fused silica column. Twenty-three constituents were identified with alpha-phellandrene as the major constituent (53%). Electron-beam irradiation of M. myristica did not significantly affect the volatile constituent profile at 15 kGy. Except alpha-thujene, which was increased from 7.18% to 16.76%, the most affected constituents were those that constitute less than 0.10% of the oil. Irradiation could be an effective way for decontamination of M. myristica. PMID- 22054413 TI - Chronic antibody-mediated rejection is reduced by targeting B-cell immunity during an introductory period. AB - Transplantation across blood group antigen and human leukocyte antigen (HLA) barriers are immunologically high risk. Both splenectomy and rituximab injection were developed to overcome those immunological barriers. The idea behind these treatments is to control B-cell immunity before and after renal transplantation and antibody production. Between January 2001 and December 2004, recipients underwent pretransplant double-filtration plasmapheresis (DFPP) and splenectomy at the time of transplantation in the ABO-incompatible group (ABO-I-SPX; n= 45). From January 2005 to June 2009, a low dose of rituximab was given as an alternative to splenectomy (ABO-I-RIT; n = 57). As a control group, we selected 83 cases of ABO-C living-donor kidney transplantation between January 2001 and December 2007 (ABO-C). We compared the graft survival rate and chronic antibody mediated rejection (C-AMR) rate between ABO-C and ABO-I kidney transplantation with induction treatment. C-AMR rates 2 years after the operation were 8.8, 3.5 and 28.9%, and de novo donor-specific anti-HLA antibody (DSHA) positive rates were 2.2, 1.7 and 18.1% in the ABO-I-SPX, ABO-I-RIT and ABO-C groups, respectively. The ABO-C group showed the highest rate of C-AMR and de novo DSHA. B-cell depletion protocols, such as splenectomy or rituximab administration, reduced C-AMR after kidney transplantation. PMID- 22054414 TI - Direct mapping of ionic transport in a Si anode on the nanoscale: time domain electrochemical strain spectroscopy study. AB - Local Li-ion transport in amorphous silicon is studied on the nanometer scale using time domain electrochemical strain microscopy (ESM). A strong variability of ionic transport controlled by the anode surface morphology is observed. The observed relaxing and nonrelaxing response components are discussed in terms of local and global ionic transport mechanisms, thus establishing the signal formation mechanisms in ESM. This behavior is further correlated with local conductivity measurements. The implications of these studies for Si-anode batteries are discussed. The universal presence of concentration-strain coupling suggests that ESM and associated time and voltage spectroscopies can be applied to a broad range of electrochemical systems ranging from batteries to fuel cells. PMID- 22054415 TI - Determinants of rapid weight gain during infancy: baseline results from the NOURISH randomised controlled trial. AB - BACKGROUND: Rapid weight gain in infancy is an important predictor of obesity in later childhood. Our aim was to determine which modifiable variables are associated with rapid weight gain in early life. METHODS: Subjects were healthy infants enrolled in NOURISH, a randomised, controlled trial evaluating an intervention to promote positive early feeding practices. This analysis used the birth and baseline data for NOURISH. Birthweight was collected from hospital records and infants were also weighed at baseline assessment when they were aged 4-7 months and before randomisation. Infant feeding practices and demographic variables were collected from the mother using a self administered questionnaire. Rapid weight gain was defined as an increase in weight-for-age Z-score (using WHO standards) above 0.67 SD from birth to baseline assessment, which is interpreted clinically as crossing centile lines on a growth chart. Variables associated with rapid weight gain were evaluated using a multivariable logistic regression model. RESULTS: Complete data were available for 612 infants (88% of the total sample recruited) with a mean (SD) age of 4.3 (1.0) months at baseline assessment. After adjusting for mother's age, smoking in pregnancy, BMI, and education and infant birthweight, age, gender and introduction of solid foods, the only two modifiable factors associated with rapid weight gain to attain statistical significance were formula feeding [OR = 1.72 (95%CI 1.01-2.94), P = 0.047] and feeding on schedule [OR = 2.29 (95%CI 1.14-4.61), P = 0.020]. Male gender and lower birthweight were non-modifiable factors associated with rapid weight gain. CONCLUSIONS: This analysis supports the contention that there is an association between formula feeding, feeding to schedule and weight gain in the first months of life. Mechanisms may include the actual content of formula milk (e.g. higher protein intake) or differences in feeding styles, such as feeding to schedule, which increase the risk of overfeeding. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN12608000056392. PMID- 22054416 TI - Complete and safe resection of challenging retroperitoneal tumors: anticipation of multi-organ and major vascular resection and use of adjunct procedures. AB - BACKGROUND: Retroperitoneal tumors are often massive and can involve adjacent organs and/or vital structures, making them difficult to resect. Completeness of resection is within the surgeon's control and critical for long-term survival, particularly for malignant disease. Few studies directly address strategies for complete and safe resection of challenging retroperitoneal tumors. METHODS: Fifty six patients representing 63 cases of primary or recurrent retroperitoneal tumor resection between 2004-2009 were identified and a retrospective chart review was performed. Rates of complete resection, use of adjunct procedures, and perioperative complications were recorded. RESULTS: In 95% of cases, complete resection was achieved. Fifty-eight percent of these cases required en bloc multi organ resection, and 8% required major vascular resection. Complete resection rates were higher for primary versus recurrent disease. Adjunct procedures (ureteral stents, femoral nerve monitoring, posterior laminotomy, etc.) were used in 54% of cases. Major postoperative complications occurred in 16% of cases, and one patient died (2% mortality). CONCLUSIONS: Complete resection of challenging retroperitoneal tumors is feasible and can be done safely with important pre- and intraoperative considerations in mind. PMID- 22054418 TI - Defining the role of TRIP6 in cell physiology and cancer. AB - Integrating signals from the ECM (extracellular matrix) via the cell surface into the nucleus is an essential feature of multicellular life and often malfunctions in cancer. To date many signal transducers known as shuttle proteins have been identified that act as both: a cytoskeletal and a signalling protein. Here, we highlight the interesting member of the Zyxin family TRIP6 [thyroid receptor interactor protein 6; also designated ZRP-1 (zyxin-related protein 1)] and review current literature to define its role in cell physiology and cancer. TRIP6 is a versatile scaffolding protein at FAs (focal adhesions) involved in cytoskeletal organization, coordinated cell migration and tissue invasion. Via its LIM and TDC domains TRIP6 interacts with different components of the LPA (lysophosphatidic acid), NF-kappaB (nuclear factor kappaB), glucocorticoid and AMPK (AMP-activated protein kinase) signalling pathway and thereby modulates their activity. Within the nucleus TRIP6 acts as a transcriptional cofactor regulating the transcriptional responses of these pathways. Moreover, intranuclear TRIP6 associates with proteins ensuring telomere protection and hence may contribute to genome stability. Accordingly, TRIP6 is engaged in key cellular processes such as cell proliferation, differentiation and survival. These diverse functions of TRIP6 are found to be dysregulated in various cancers and may have pleiotropic roles in tumour initiation, tumour growth and metastasis, which turn TRIP6 into an attractive candidate for cancer diagnosis and targeted therapy. PMID- 22054419 TI - Jumping the barrier: VE-cadherin, VEGF and other angiogenic modifiers in cancer. AB - The endothelial barrier controls the passage of fluids, nutrients and cells through the vascular wall. This physiological function is closely related to developmental and adult angiogenesis, blood pressure control, as well as immune responses. Moreover, cancer progression is frequently characterized by disorganized and leaky blood vessels. In this context, vascular permeability drives tumour-induced angiogenesis, blood flow disturbances, inflammatory cell infiltration and tumour cell extravasation. Although various molecules have been implicated, the vascular endothelial adhesion molecule, VE-cadherin (vascular endothelial cadherin), has emerged as a critical player involved in maintaining endothelial barrier integrity and homoeostasis. Indeed, VE-cadherin coordinates the endothelial cell-cell junctions through its adhesive and signalling properties. Of note, many angiogenic and inflammatory mediators released into the tumour microenvironment influence VE-cadherin behaviour. Therefore restoring VE cadherin function could be one very promising target for vascular normalization in cancer therapies. In this review, we will mainly focus on recent discoveries concerning the molecular mechanisms involved in modulating VE-cadherin plasticity in cancer. PMID- 22054420 TI - Enhancement of humoral immunity in mice by coupling pUCpGs10 and aluminium to the HCV recombinant immunogen. AB - AIM: To investigate the enhancement of humoral immunity when CpG ODN (cytidine phosphate guanosine oligodeoxynucleotides) and aluminium adjuvants are complexed with the HCV (Hepatitis C virus) recombinant immunogen in mice. METHODS: After immunizing Balb/c mice with the recombination HCV antigen adjuvanted with pUCpGs10 and/or aluminium(antigen+CpG+alum, antigen+CpG, antigen+alum, antigen+PBS), enzyme-linked immunosorbent assay (ELISA) was used to measure the specific serum antibody titers of IgG, to determine the neutralization response to various peptide genotypes, and to determine the concentration of IL-6 and IL 10 in supernatants of in vitro cultured splenic lymphocytes. Enzyme-linked immunospot assay (ELISPOT) was used to quantify the non-specific and specific splenic antibody-secreting cells (ASCs), and flow cytometry (FCM) determined the ratio of different splenic lymphocytes. The serum of rabbits immunized with the recombinant pBVGST/HVR1 antigen immunoprecipitated the HCV isolated from 12 patients' serum. RESULTS: The sera antibody titers were 1:51200, 1:9051, 1:18102, 1:6400 respectively after the final immunization and demonstrated good neutralization responses to the six gene peptide containing 1a, 1b, 2a, 3a, 4a and 6a. The aluminum adjuvant increased the population of both specific ASCs (P < 0.01) and total ASCs(P < 0.05), with a proportional rise in concentrations of CD19+CD27+ (P < 0.05), as well as levels of IL-6, IL-10 (P < 0.05) in splenic lymphocytes. The results clearly indicated a significantly higher number of CD19+CD38+ splenic lymphocytes with the aluminum and pUCpGs10 adjuvant present compared to the control group(P < 0.05). Anti-HVR1 antibody in induced mice can cross-reactively capture HCV particles (10/12). CONCLUSIONS: 1. The aluminum adjuvant induces a potent Th2-biased immune response by increasing both the populations of specific and total ASCs and the ratio of CD19+CD27+ cells. 2. The pUCpGs10 complexed with the aluminum adjuvant boosts the population of plasma cells and increase the efficiency of the immune response. 3. The two adjuvants have synergistic effects on humoral immunity. 4. The recombinant HVR1 protein has the possibility of generating broadly reactive anti-HVR1 antibody. PMID- 22054421 TI - Black tea theaflavins inhibit formation of toxic amyloid-beta and alpha-synuclein fibrils. AB - Causal therapeutic approaches for amyloid diseases such as Alzheimer's and Parkinson's disease targeting toxic amyloid oligomers or fibrils are still emerging. Here, we show that theaflavins (TF1, TF2a, TF2b, and TF3), the main polyphenolic components found in fermented black tea, are potent inhibitors of amyloid-beta (Abeta) and alpha-synuclein (alphaS) fibrillogenesis. Their mechanism of action was compared to that of two established inhibitors of amyloid formation, (-)-epigallocatechin gallate (EGCG) and congo red (CR). All three compounds reduce the fluorescence of the amyloid indicator dye thioflavin T. Mapping the binding regions of TF3, EGCG, and CR revealed that all three bind to two regions of the Abeta peptide, amino acids 12-23 and 24-36, albeit with different specificities. However, their mechanisms of amyloid inhibition differ. Like EGCG but unlike congo red, theaflavins stimulate the assembly of Abeta and alphaS into nontoxic, spherical aggregates that are incompetent in seeding amyloid formation and remodel Abeta fibrils into nontoxic aggregates. When compared to EGCG, TF3 was less susceptible to air oxidation and had an increased efficacy under oxidizing conditions. These findings suggest that theaflavins might be used to remove toxic amyloid deposits. PMID- 22054422 TI - Highly sensitive analysis of boron and lithium in aqueous solution using dual pulse laser-induced breakdown spectroscopy. AB - We have applied a dual-pulse laser-induced breakdown spectroscopy (DP-LIBS) to sensitively detect concentrations of boron and lithium in aqueous solution. Sequential laser pulses from two separate Q-switched Nd:YAG lasers at 532 nm wavelength have been employed to generate laser-induced plasma on a water jet. For achieving sensitive elemental detection, the optimal timing between two laser pulses was investigated. The optimum time delay between two laser pulses for the B atomic emission lines was found to be less than 3 MUs and approximately 10 MUs for the Li atomic emission line. Under these optimized conditions, the detection limit was attained in the range of 0.8 ppm for boron and 0.8 ppb for lithium. In particular, the sensitivity for detecting boron by excitation of laminar liquid jet was found to be excellent by nearly 2 orders of magnitude compared with 80 ppm reported in the literature. These sensitivities of laser-induced breakdown spectroscopy are very practical for the online elemental analysis of boric acid and lithium hydroxide serving as neutron absorber and pH controller in the primary coolant water of pressurized water reactors, respectively. PMID- 22054423 TI - Flow cytometry-assisted Monte Carlo simulation predicts clonogenic survival of cell populations with lognormal distributions of radiopharmaceuticals and anticancer drugs. AB - PURPOSE: Although the distribution of therapeutic agents within cell populations may appear uniform at the macroscopic level, the distribution at the multicellular level is nonuniform. As such, the mean agent concentration in tissue may not be a suitable quantity for use in predicting biological effects. Failure in chemotherapy and targeted radionuclide therapy has been attributed, in part, to the ubiquity of lognormal distributions of therapeutic agents. To improve capacity to predict biological response, this work develops approaches that determine the fate of a cell population on a cell-by-cell basis. METHODS: Incorporation of the alpha-particle emitting radiochemical ((210)Po-citrate) and two anticancer drugs (daunomycin and doxorubicin) by Chinese hamster V79 cells was determined using flow cytometry. Monte Carlo simulation was used to estimate cell survival on the bases of mean and individual cell incorporation of each cytotoxic agent. The interrelationships between the Monte Carlo simulated cell survival and clonogenic cell survival were evaluated. RESULTS: Cell survival obtained by Monte Carlo simulation based on individual cell incorporation was in good agreement with clonogenic cell survival for all agents. However, the agreement was poor when the simulation was carried out using the mean cell incorporation of the agents. CONCLUSION: These data indicate that, with the aid of flow cytometry, Monte Carlo simulations can be used to predict the toxicity of therapeutic agents in a manner that takes into account the effects of lognormal and other nonuniform distributions of agents within cell populations. PMID- 22054425 TI - Meat: Current developments and future status. PMID- 22054424 TI - In vitro and in vivo behaviour of sympatric Leishmania (V.) braziliensis, L. (V.) peruviana and their hybrids. AB - Leishmania (Viannia) braziliensis is the main cause of highly disfiguring mucocutaneous leishmaniasis (MCL) in South America. The related species L. (V.) peruviana has only been identified in simple cutaneous lesions (CL). Hybrids between L. braziliensis and L. peruviana have been reported although genetic exchange in Leishmania is considered to be rare. Here we compared growth in vitro, adaptive capacity under thermal and oxidative stress and behaviour in a hamster model, of L. braziliensis, L. peruviana, and their putative hybrids. At 24 degrees C, the optimal temperature for in vitro growth, L. braziliensis had the highest growth rate. In in vitro studies hybrid clones presented heterogeneous phenotypes, from slower growth rates, similar to L. peruviana, to higher growth rates, as observed in L. braziliensis. Hamsters infected with hybrid strains, presented the highest parasite densities and aggressive relapses at a later stage of infection. Hybrids generally presented higher plasticity and phenotypic diversity than the putative parental species, with potential eco epidemiological implications, including an impact on the success of disease control. PMID- 22054426 TI - Postmortem breakdown of ATP and glycogen in ground muscle: A review. AB - The postmorte metabolism of ATP and glycogen in ground bovine muscle (in some cases also in rabbit muscle) was studied. At pH 7 protons released during postmortem glycolysis are bound by the phosphorylation of ADP to ATP and are liberated during enzymic hydrolysis of ATP. At lower pH values the protons are immediately released during glycolysis. Not more than 10% of the total drop in pH postmortem is due to protons liberated by the hydrolysis of ATP present in the tissue at death. Half of the buffering capacity of bovine muscle is caused by the myofibrillar proteins. The myofibrillar ATPases, rather than the membrane ATPases, seem to predominate in hydrolysing ATP postmortem in the intact as well as in the ground muscle. The rate of the breakdown of ATP determines the rate of postmortem glycolysis. Phosphofructokinase and, to a lesser extent, phosphorylase play the major role in the control of glycolytic metabolite levels in ground muscle. The mean values of glycogen recovery, obtained by measuring all glycolytic metabolites and lactate, indicate a general stoichiometric relationship in ground tissue, although several muscles did not fit in the scheme. Grinding of the prerigor muscle causes an accelerated hydrolysis of ATP and ADP, resulting in a faster increase in the IMP concentration and in an accelerated glycolysis. The increase in the turnover of ATP by grinding might be due to a faster release of Ca(++) ions from the damage sarcoplasmic reticulum. Addition of sodium chloride (2-4%) to the ground pregidor muscle causes an increase in the rate of the breakdown of ATP to IMP. NaCl changes the steady state of glycolysis without a major change in the rate of glycogen breakdown. The stimulation of phosphofructokinase observed is probably due to the faster disapearance of ATP in the presence of NaCl. The faster turnover of ATP could be due to an enhanced release of Ca(++) ions from the sarcoplasmic reticulum by exchange against Na(+) After several hours postmortem an inhibition of glycolysis occurs in the salted tissue which is probably due to a denaturation of glycolytic enzymes by the combined effect of low pH (<6) and high ionic strength. The high water-holding capacity of prerigor salted ground beef does not decrease postmortem in spite of the high rate of ATP breakdown. This effect can be explained by an inhibition of rigor mortis in the fibre fragments caused by the combined effect of ATP, high pH and salt ions. Addition of diphosphate to the prerigor ground tissue in the absence or presence of added NaCl results in an acceleration of ATP and glycogen breakdown. A hypothesis for the high ATP turnover is discussed. The higher rate of glycogen breakdown in the presence of diphosphate is caused mainly by an acceleration of the phosphofructokinase step. A rate limitation, by diphosphate, in the glyceraldehyde-3-phosphate dehydrogenase step and/or the following glycolytic steps was also observed. PMID- 22054427 TI - Lipid and myoglobin oxidation in pork stored in oxygen- and carbon dioxide enriched atmospheres. AB - The formation of malonaldehyde and metmyoglobin in pork muscles stored in oxygen- and carbon dioxide-enriched atmospheres at 1 degrees C was followed. The formation of metmyoglobin at the surface of the muscles was independent of carbon dioxide concentration. However, increased oxygen concentration caused a significant decrease in the rate of metmyoglobin formation; the surface concentration of metmyoglobin was below 30% even after 15 days' storage in 80% oxygen/20% carbon dioxide. Lipid oxidation, as measured by malonaldehyde production (TBA Number), occurred at the same rate in air an mixtures containing 80, 90 and 100% oxygen. In some muscles, the rate was such that rancidity was apparent within 6 days at 1 degrees C and, for pork, lipid oxidation, and not bacterial spoilage or metmyyoglobin formation, may be the limiting factor in the use of oxygen-containing atmospheres for storage. PMID- 22054428 TI - Tensile strength and the tenderness of beef sternomandibularis muscle. AB - In their relationship to shortening, the tensile strength of cooked meat along the fibres and the shearing force measured across them are strikingly similar. Both increase to maximum values at 40% shortening before falling by a half with an approach to 60% shortening. A high correlation (r = 0.81) exists between the two sets of values, whether toughness is increased by cold shortening or reduced by ageing. The mechanical strength of meat along its fibres is therefore a simple measure of tenderness and a useful basis for relating muscle structure to stength. PMID- 22054429 TI - Studies on the meat production characteristics of Botswana goats and sheep-Part I: Sampling, methods and materials, and measurements on the live animals. AB - A carcase evaluation exercise was carried out on various groups of smallstock (goats and sheep) which are of importance to the meat industry in Botswana, and which formed part of a larger overall project designed to improve meat production from indigenous smallstock. The main objective was to provide background data on various body and carcase characteristics, from which subsequent selection, breeding and improved management could be evaluated and monitored. The data collected was concerned with: the external dimensions and weights of the live animals; the composition of the slaughtered animals in terms of the weights of offal parts and carcase weight; the dimensions of the carcases and the composition of the carcases in terms of the weights of their component joints; the quantity of muscle and fat on the carcases and the distribution and relative proportions of these tissues throughout the carcases. A total of 145 goats and 112 sheep were used in the investigation. The present paper discusses the sampling of the goats and shep, outlines the methods used and presents data on external linear measurements and liveweights of the animals. PMID- 22054430 TI - Expression of Aeromonas caviae polyhydroxyalkanoate synthase gene in Burkholderia sp. USM (JCM15050) enables the biosynthesis of SCL-MCL PHA from palm oil products. AB - AIMS: Burkholderia sp. USM (JCM15050) isolated from oil-polluted wastewater is capable of utilizing palm oil products and glycerol to synthesize poly(3 hydroxybutyrate) [P(3HB)]. To confer the ability to produce polymer containing 3 hydroxyhexanoate (3HHx), plasmid (pBBREE32d13) harbouring the polyhydroxyalkanoate (PHA) synthase gene of Aeromonas caviae (phaC(Ac)) was transformed into this strain. METHODS AND RESULTS: The resulting transformant incorporated approximately 1 +/- 0.3 mol% of 3HHx in the polymer when crude palm kernel oil (CPKO) or palm kernel acid oil was used as the sole carbon source. In addition, when the transformed strain was cultivated in the mixtures of CPKO and sodium valerate, PHA containing 69 mol% 3HB, 30 mol% 3-hydroxyvalerate and 1 mol% 3HHx monomers was produced. Batch feeding of carbon sources with 0.5% (v/v) CPKO at 0 h and 0.25% (w/v) sodium valerate at 36 h yielded 6 mol% of 3HHx monomer by controlled-feeding strategies. CONCLUSIONS: Burkholderia sp. USM (JCM15050) has the metabolic pathways to supply both the short-chain length (SCL) and medium chain length (MCL) PHA monomers. By transforming the strain with the Aer. caviae PHA synthase with broader substrate specificity, SCL-MCL PHA was produced. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study demonstrating the ability of transformant Burkholderia to produce P(3HB-co-3HHx) from a single carbon source. PMID- 22054431 TI - The use of video image analysis for quantitative measurement of fatness in meat: Part 2-Comparison of VIA, visual assessment and total chemical fat estimation in a commercial environment. AB - The use of video image analysis as a predictor of visual fat and lean has been tested in a commercial environment. Results from scanning a 2250 kg consignment of beef showed that the system is reliable and the results reproducible. After pre-breaking, the whole sample was rapidly measured. Scanning of frozen slices produced values only 1% different from those obtained from the pre-broken meat. Scanning small samples (less than 25% of the total) was not representative of the total consignment because of the material variability. Fat measurements determined by VIA were considerably different from those obtained by visual assessment. At the same time, the inconsistency of conventional commercial sampling techniques was highlighted. The relationship between VIA and total chemical fat was also investigated. Once corrections had been made for the non visible fat content of the meat, VIA results were comparable with chemical fat analysis for any given cut. PMID- 22054432 TI - The properties of glycerol-extracted Longissimus dorsi muscle fibres and myofibrils taken from beef carcasses during post-mortem conditioning. AB - Muscle samples from beef Longissimus dorsi (LD) were conditioned inv vacuo at 10 degrees C for up to 21 days and then stored in a glycerol-extracted state at -20 degrees C to determine how their mechanical properties were altered by the conditioning process. Muscle fibres were progressively more difficult to dissect as conditioning proceeded, but those dissected showed isometric mechanical tension in the presence of Ca(2+), relaxation in the absence of Ca(2+) and calcium sensitivity which did not vary with conditioning up to 8 days. Myofibrils prepared from the same conditioned tissue showed slight changes with conditioning time, namely an initial rise in Ca(2+)-activated ATPase followed by a later fall, a slow rise in ATPase in the absence of Ca(2+) and an increase in Ca(2+) sensitivity. It is concluded that preparation of muscle fibres from conditioned tissue selects undamaged fibres, and that conditioning proceeds by the progressive increase in number of conditioned fibres within each of which conditioning has taken place relatively rapidly. PMID- 22054433 TI - Sex, age and breed related changes in bovine testosterone and intramuscular collagen. AB - Longissimus muscle biopsies were obtained from forty bulls and steers representing Charolais, Simmental, Angus and Hereford breeds at 6, 9, 12, 15 and 18 months of age to evaluate the influence of age, breed and sex on the biosynthesis of muscle collagen. Blood samples were collected from each animal at each time period. The blood serum was harvested and assayed for concentrations of testosterone. Total collagen, soluble collagen and insoluble collagen were obtained on each sample. Soluble collagen and testosterone levels were significantly influenced by breed, sex and animal age. Total collagen levels were significantly affected by sex and age. Total collagen and testosterone levels peaked at 12 months of age. Breeds were ranked identically for total collagen and testosterone levels at 12 months. These data indicate that bulls are different from steers in synthesis of intramuscular collagen at or near 12 months of age. The increased synthesis of collagen appears to be influenced by testosterone or some other event associated with puberty. The mechanism of this action remains unclear. PMID- 22054434 TI - Carbon dioxide evolution of refrigerated meat. AB - The carbon dioxide (CO(2)) evolution from pork loins stored in air or nitrogen at 5 degrees C was measured. The loins were cut immediately after slaughter ('pre rigor meat.'), or approximately 20 h after slaughter ('post-rigor meat'). CO(2) evolution rate was highest during the first day (2.3 * 10(-3)mlcm(-2)h(-1)) and then declined to approximately 0.5 * 10(-3)mlcm(-2)h(-1). The rate was fairly constant during this later phase, and there were no large differences between aerobically and anaerobically stored meat, or between pre-rigor meat and post rigor meat. Four hypotheses for the origin of the CO(2) evolution are discussed: (1) diffusion from a pre-formed pool in the meat; (2) aerobic energy metabolism of the meat cells; (3) other biochemical reactions of the meat cells; and (4) microbial activity. None of the hypotheses completely supports the experimental results of the investigation. The impact of these findings on the vacuum packaging of meat is discussed. PMID- 22054435 TI - Tenderisation of meat by pressure-heat involves weakening of the gap filaments in the myofibril. AB - These results confirm previous Australian experience that pressure-heat (P-H) treatment tenderises rigor meat effectively only after considerable periods at elevated temperatures; that prior ageing abolishes the effect; and that cold shortened meat is effectively tenderised. Yield point is also profoundly affected by P-H, although this effect is not related to tenderness. As predicted by the new G-filament theory of meat tenderness, P-H greatly weakens the G-filaments. These then break on extension by 50% but not if subsequently cooked. However the tensile properties of cooked meat support the weakening of G-filaments. A problem is that mild P-H treatments which are ineffective at tenderising, produce the same histological damage as harsher tenderising treatments. This paper reviews the considerable body of results on the P-H treatment of rigor meat that have now accumulated. The effects of pressure on the various filaments is discussed. The nature of the changes induced in the G-filaments remains obscure. PMID- 22054436 TI - 'Ageing' of cold shortened meat depends on the criterion. AB - Although cold shortened muscles show little decline in shear force during ageing, they do, like unshortened muscles, undergo a drastic reduction in yield point. The differing responses to the two criteria arise from the involvement of different structural elements. Our previous claim, that yield point is highly sensitive to ageing and reflects changes in tenderness, remains valid for unshortened muscles, but is clearly inappropriate to cold shortened samples. PMID- 22054439 TI - [A new analysis tool of salivary gland tumors: looking for specific translocations]. PMID- 22054440 TI - [Perspectives: FISH on cytological samples]. PMID- 22054441 TI - [Semiology of cervical glandular cell abnormalities]. PMID- 22054442 TI - [Adenocarcinoma of uterine cervix. Difficulties in the diagnosis of early forms and cyto-colpo-histological correlations]. PMID- 22054443 TI - [Treatment of adenocarcinoma in situ of the uterine cervix]. PMID- 22054444 TI - [Standardized pathology report for melanoma. WHO classification evolution]. PMID- 22054445 TI - [Immunohistochemistry contribution in melanocytic lesions analysis]. PMID- 22054446 TI - [Molecular diagnostic contribution in melanocytic lesions analysis (FISH/CGH)]. PMID- 22054447 TI - [Clinical practice evolution in dermatology: consequences for the pathologist]. PMID- 22054449 TI - [Melanoma and search for therapeutic targets]. PMID- 22054451 TI - Update on the Gleason grading system. PMID- 22054452 TI - [WHO Classification of digestive tumors: the fourth edition]. PMID- 22054453 TI - [How to develop quality indicators in cytology?]. PMID- 22054454 TI - [Signal transduction and its targeting: the researcher point of view, example of hematologic diseases]. PMID- 22054456 TI - [Signal transduction and its targeting from the cancer molecular genetic platform: applications and perspectives in pulmonary pathology]. PMID- 22054457 TI - [In practice for the pathologist: practical and technical limitations]. PMID- 22054458 TI - [Ki67, nucleolus and cancer]. PMID- 22054459 TI - [How to evaluate Ki67]. PMID- 22054460 TI - [When to use Ki67]. PMID- 22054461 TI - [Ki67 and neuroendocrine tumors]. PMID- 22054462 TI - [Proliferation evaluation by measuring Ki67 in breast neoplasms]. PMID- 22054463 TI - [C. elegans: the power of simplicity]. PMID- 22054465 TI - [The avian model in developmental biology and physiopathology]. PMID- 22054466 TI - [Murine cutaneous melanoma models. Importance of the genetic background]. PMID- 22054468 TI - [Clinical, pathologic and molecular characteristics of pulmonary high-grade neuroendocrine tumors]. PMID- 22054469 TI - [Pathologic diagnostic for a primary of metastatic neuroendocrine tumor]. PMID- 22054470 TI - [Diagnosis, staging and follow-up of malignant neuroendocrine tumors: role of radiology]. PMID- 22054471 TI - [Diagnosis, staging and follow-up of neuroendocrine tumors: role of somatostatin receptors scintigraphy]. PMID- 22054472 TI - [Management of metastatic neuroendocrine tumors]. PMID- 22054473 TI - [Sino nasal polyps: true and false tumors]. PMID- 22054474 TI - [Securising diagnosis in pathology in 2011. The diagnostic error: between rhetoric and reality]. PMID- 22054475 TI - [WHO classification of salivary gland tumors: instructions]. PMID- 22054476 TI - [Fine needle aspiration in management of salivary gland tumors. The clinician point of view]. PMID- 22054479 TI - The American Academy of Gold Foil Operators and Dental School Education. PMID- 22054477 TI - Effect of the aetiology and severity of liver disease on oral health and dental treatment prior to transplantation. AB - Elimination of dental infection foci has been recommended before liver transplantation (LT) because lifelong immunosuppression may predispose to infection spread. Association between pre-LT oral health and the aetiology and severity of chronic liver disease (CLD) was investigated retrospectively. A total of 212 adult patients (median age 51.1) who had received LT during 2000-2006 in Finland were included. Their oral health had been pre-operatively examined. Patients were divided into seven different CLD groups. Common indications for LT were primary sclerosing cholangitis (PSC 25.5%), alcohol cirrhosis (ALCI 17.5%) and primary biliary cirrhosis (PBC 14.6%). Patients were also categorized by the Model for End stage Liver Disease (MELD) scoring system. Medical, dental and panoramic jaw x-ray data were analysed between groups. PBC patients had the lowest number of teeth with significant difference to PSC patients (19.7 vs. 25.6, P < 0.005, anova, t-test). ALCI patients had the highest number of tooth extractions with significant difference in comparison to PSC patients (5.6 vs. 2.5, P < 0.005). Lower MELD score resulted in fewer tooth extractions but after adjusting for several confounding factors, age was the most important factor associated with extractions (P < 0.005). The aetiology of CLD associated with the oral health status and there was a tendency towards worse dental health with higher MELD scores. PMID- 22054480 TI - Notation: PMID- 22054483 TI - CORRECTION. PMID- 22054485 TI - Influence of sampling factors on canine sperm motility parameters measured by the Sperm Class Analyzer. AB - The aim of the present study was to investigate the effect of different technical settings and semen processing on sperm motility parameters measured by the Sperm Class Analyzer (SCA). Semen was collected from 3 dogs, pooled, and diluted in phosphate buffered saline and subsequently assessed by the SCA for the different sperm motility characteristics. The data were statistically analyzed by ANOVA and the repeatability was assessed by coefficient of variation (CV). After a principal component analysis, the reliability was determined with intra-class correlation coefficient (ICC). In experiment 1, the CV's were below 10% for all evaluated parameters. Significant differences (P < 0.05) were found between the different sperm concentrations (25, 50, and 75 x 10(6) spermatozoa/ml) in all of the motion parameters assessed, yielding the highest ICC (0.81) at 25 x 10(6) spermatozoa/ml. No significant differences (P > 0.05) in SCA read-outs were found between the number of microscopic fields captured (1, 2, 3, 4, or 5 fields), yielding the highest ICC (0.83) when 3 fields were captured. No significant differences (P > 0.05) in motility parameters were found between the number of cells analyzed in each field (20, 50, and 100 spermatozoa) with the exception of beat cross frequency. Reliability of the SCA was good (ICC = 0.71 to 0.90) for all motility measurements when 20 (ICC = 0.89) or 50 (ICC = 0.77) cells were captured in each field, but only just acceptable (ICC = 0.51 to 0.70) when 100 cells were counted (ICC = 0.67). The frame settings significantly (P < 0.05) influenced most of the measured motility characteristics. Scanning 60 frames at a frame rate of 30 Hz improved the reliability of the results (ICC = 0.92). In conclusion, we suggest that the measurements with the SCA are ideally performed at a sperm concentration of 25 x 10(6) spermatozoa/ml, counting at least 100 cells in three microscopic fields. We also propose that the SCA should analyze 60 frames at 30 Hz to yield consistent results of a set of measurements or a measuring instrument thus obtaining reliable motility results. PMID- 22054486 TI - Myofibrils, sarcoplasmic reticulum and phosphorylase kinase of Pietrain and Large White-landrace pigs. AB - Comparison of fast and slow twitch myofibril preparations by SDS-gel electrophoresis showed no significant differences between Large White and Pietrain pigs. No variants of parvalbumins or calsequestrin (calcium binding proteins) were found. Pietrain phosphorylase kinase has a greater stimulating activity on porcine phosphorylase than does Large White phosphorylase kinase. PMID- 22054484 TI - A high recombination rate in eusocial Hymenoptera: evidence from the common wasp Vespula vulgaris. AB - BACKGROUND: High recombination rates have previously been detected in two groups of eusocial insects; honeybees and ants. In this study we estimate recombination rate in a eusocial wasp Vespula vulgaris that represents a third phylogenetic lineage within eusocial hymenopterans. RESULTS: A genetic linkage map of V. vulgaris based on 210 markers shows that the total map length is 2129 cM and the recombination rate is 9.7 cM/Mb (or 103 kb/cM). The present estimate in V. vulgaris is somewhat smaller than in the honeybee Apis mellifera and intermediate between the estimates from two ant species (Acromyrmex echinatior, Pogonomyrmex rugosus). Altogether, the estimates from these eusocial species are higher than in any other insect reported so far. CONCLUSIONS: [corrected] The four species (V. vulgaris, A. mellifera, A. echinatior, P. rugosus) are characterized by advanced eusociality with large colonies, clear queen-worker dimorphism and well developed task specialization. They also have colonies with a single, normally multiply inseminated (polyandrous) queen. Benefits of genotypic diversity within colonies (e.g. through improved task specialization or pathogen and parasite resistance) may have selected for both polyandry and high recombination rate in such advanced eusocial insects. PMID- 22054487 TI - Residual blood in lamb muscles. AB - The effect of slaughter method on the residual blood content of the M. longissimus dorsi, the microbiological status of the meat and its tenderness was examined with lambs. There were no differences in any of the characteristics examined between the various stunning procedures used, even though there were marked differences in the amount of blood collected after slaughter. PMID- 22054488 TI - Effect of electrical stunning method and cardiac arrest on bleeding efficiency, residual blood and blood splash in lambs. AB - Five hundred and fifty-nine Southdown-Romney cross lambs were used in a comparison of the efficiency of bleeding animals slaughtered by one of three different methods. The main comparison was between spear stuck lambs that had been electrically stunned by either head application or a head-back method. In addition, some unstunned lambs were slaughtered by the traditional New Zealand gash cutting method, no longer used by industry but known to produce well bled carcasses. There was no difference in blood obtained during a 120-s bleeding time between the unstunned and head stunned lambs. For the head-back stunned lambs little, if any, of the blood not collected at bleeding remained in the carcass after dressing despite the fact that these animals released only 46% of the weight of blood recorded from the head stunned lambs during the bleeding time. The head-back stunning method markedly decreased the incidence of carcass blood splash in comparison with the splash observed in lambs stunned by the head application method. PMID- 22054489 TI - Osmotic properties of post-rigor beef muscle. AB - The osmotic pressure of beef sternomandibularis and psoas muscles ranged from 480 to 540 mOs, which is almost twice that of pre-rigor muscle (about 300 mOs). The post-rigor osmotic pressure appears to be satisfactorily explained by the low molecular weight components. Muscle samples were soaked at 2 degrees C for 24 h in various solutions and sample weight changes were recorded. Samples soaked in buffered mannitol solutions exhibited weight changes indicative of predictable osmotic behaviour. Those samples soaked in buffered salt solutions (KCl, NaCl), however, exhibited dramatic increases in weight, irrespective of the solute concentration. The reasons for this are not clear. These results indicative that the use of salt solutions, such as 0.15 m KCl, for studies on post-rigor muscle is suspect and conclusions from such studies may be unfounded. PMID- 22054490 TI - The properties of connective tissue membrane and pig skin as raw materials for cooked sausage. AB - Pig skin and epimysial membrane from young bulls were comminuted in a colloid grinder and mixed with water and additives. The resultant mixture was heated in a water bath to give an internal temperature of 72 degrees C, and centrifuged while still hot. Such variations in the amount of water added, the salt content, the phosphate content and the pH value as are possible in cooked sausage heated to over 65 degrees C during processing did not cause marked changes in the amount of water bound by the connective tissues, the amount of dissolved protein or the gel strength of the liquid released from the connective tissues. As the temperature rose the amount of bound water dropped, but the amount of dissolved protein and the gel strength increased. The liquid released from the connective tissue membranes formed a gel at 32 degrees C and re-melted at 49 degrees C. For pig skin, the corresponding temperatures were 23 degrees C and 47 degrees C. On the basis of this study it appears that connective tissue may be important for the water-binding capacity and firmness of cold sausage. The connective tissue membranes obtained from young bulls and pig skin are of roughly equal value in this respect, although the gel formed from connective tissue membrane is tougher. PMID- 22054491 TI - A national survey of the weight loss in pig carcasses between slaughter and 24 hours post mortem. AB - A national survey was carried out in Great Britain in 1978/79 to determine the weight loss occurring in pig carcasses between slaughter and 24 hours post mortem. A total of 20,600 carcasses were measured over a 12-month period, the sample covering forty-eight slaughtering plants and the main market weights of pig. At 24 hours post mortem, the overall mean weight loss was estimated to be 2.27% of the hot weight. The figure differed little between market weights or between times of the year, but there were important differences between slaughtering plants. PMID- 22054492 TI - Proteolytic degradation of connectin, a high molecular weight myofibrillar protein, during heating of meat. AB - When homogenised muscle (pH 5.5) was heated at 55 degrees C, connectin was extensively degraded, whereas actin and myosin heavy chains were apparently unaffected. It was concluded that carboxyl proteases (e.g. cathepsin D) were largely responsible, because the breakdown of connectin was inhibited by the addition of pepstatin. When whole muscle samples were heated at 50-70 degrees C, degradation of connectin was inversely related to the ultimate pH of the source muscle, again indicating the role of carboxyl proteases. The greater activity of carboxyl proteases in tissues from older animals was apparently responsible for the more extensive degradation of connectin in muscle from older sheep. Because connectin is extensively degraded in cooked meat, it is unlikely to contribute to meat toughness. PMID- 22054493 TI - The role of non-haem proteins in meat haemoprotein digestion. AB - The influence of additional protein on the in vitro digestion of haem compounds was investigated. When either (59)Fe-labelled haemoglobin in blood or unlabelled purified haemoglobin were digested in vitro, the formation of low molecular weight (< 10,000), dialysable, iron degradation products was very limited (<18% of the total iron) and consisted mostly of haematin compounds. The presence of additional protein, in the form of bovine serum albumen or gelatin, greatly increased the formation of low molecular weight (<10,000) degradation products; the increase being proportional to the concentration and type of added protein. In these systems approximately two-thirds of the low molecular weight iron compounds were non-haematin in character. However, the digestion of aqueous muscle extracts resulted in the greatest formation of low molecular weight (<10,000) iron degradation products (>70% of the total iron), nearly all of which were non-haematin compounds. A hypothesis is presented explaining how haemoprotein degradation occurs in meat and related systems during normal physiological digestion. PMID- 22054494 TI - The use of kidneys with small renal tumors for transplantation: who is taking the risk? AB - The ever-increasing disparity between the number of organs available for transplant and the need for organs drives further exploration into the use of compromised or marginal donors. There is now an emerging advocacy for the use of kidneys with existing tumors, which may be rendered tumor free after surgical excision and reconstruction. This practice is based on reliable data that renal cancers <3 cm in diameter behave with minimal malignant potential and likelihood of transmission to the immunosuppressed recipient. However, in the case of live donors this creates a potential ethical conflict between those treating patients with renal masses and those with an interest in renal donation. The best available treatment for patients with a small renal tumor is a form of nephron sparing tumor excision or ablation, as this approach provides for the maximum amount of residual kidney function and enhances survival. Thus, patients newly diagnosed with small renal tumors should be referred to centers with expertise in nephron sparing techniques, not transplant centers. In the case of an individual undergoing a live donor evaluation in which a small renal tumor is detected, a careful analysis of risk and benefit for the potential donor and the recipient is indicated. PMID- 22054495 TI - Muscle glycogen: Comparison of iodine binding and enzyme digestion assays and application to meat samples. AB - A rapid assay for tissue glycogen is described. Bovine liver and muscle glycogen were solubilized with perchloric acid (7-10%) and incubated with an iodine (I(2) KI) solution containing saturated CaCl(2). The optical density of the amber-brown color was determined at 460 nm. Color development was immediate, stable for up to 2 h, and was linear with respect to glycogen concentrations up to 600 MUg glycogen/ml. The iodine assay was applied to fresh, frozen, and aged bovine muscle samples and was compared to enzymic (amyloglucosidase) digestion of glycogen followed by glucose determination. The correlation between the iodine and enzyme methods was linear over the range of 0-1400 g glycogen/g tissue (corr = 0.875; P < 0.01; n = 172). The iodine binding assay can be employed with confidence as an indicator of tissue [glycogen] and is faster and more reliable than the enzyme assay. Comparison of the iodine enzyme assays on aged meat samples revealed marked decreases in muscle glycogen during the first 48 h post slaughter. The decreases were identical whether determined by iodine binding or enzyme assay. Regardless of assay method, post-mortem concentrations of glycogen in bovine sternomandibularis muscle were more variable than in longissimus dorsi samples. PMID- 22054496 TI - Humectants improve myosin extractability and water activity of raw, cured intermediate moisture meats. AB - Glycerol, propylene glycol and sorbitol were incorporated into salt-based intermediate moisture meats manufactured from porcine M. longissimus thoracis and bovine M. biceps femoris by dry curing and air drying at 4 degrees C. Moisture content and water activity (a(w)) in cured pork were reduced by the addition of propylene glycol and sorbitol. Propylene glycol was more effective than sorbitol in lowering a(w). The extractability of myosin heavy chain, used as an index of alteration of myofibrillar protein, decreased in intermediate moisture porcine meats with the addition of salt and was unaffected by sorbitol. However, use of glycerol and propylene glycol in cured and air-dried pork increased the extractability of myosin heavy chain. Whereas intact myofibrils could not be extracted from salt-cured, air-dried beef, myofibrils could be made from air dried beef cured in the presence of 10% glycol, 5% propylene glycol and 4% sorbitol. Such myofibrils contracted immediately on addition of Mg(2+)-ATP. In addition, even after storafe for 5 months, including 30 days at 25 degrees C, myosin heavy chain could be extracted from meat cured with this combination of humectants. In comparison with salt curing alone, curing meat with the above three humectants together, plus salt, results in intermediate moisture meats more like fresh meat. PMID- 22054497 TI - Effect of diet on animal performance, lipid composition of subcutaneous adipose and liver tissue of beef cattle. AB - Two trials were carried out with Brahman beef cattle to study animal performance and carcass characteristics as well as fatty acid composition of subcutaneous adipose and hepatic tissue, as influence by length of grain feeding period or a pasturing regimen. In trial 1, steers were allotted to three feedlot finishing periods (76, 104 and 146 days) after being backgrounded on pasture. Steers fed 76 days had greater average daily gains (P < 0.05) than steers fed 146 and 104 days, respectively. Carcasses of steers slaughtered after 146 days on feed had higher (P < 0.05) marbling scores, quality grades, fat over ribeye, quality yield and per cent kidney, pelvic and heart (KPH) fat than steers fed for 104 and 76 days. The proprortions of certain fatty acid of subcutaneous fat and liver tissue were influenced by the length of grain feeding. There was a marked increased in the proportion of oleic acid in both tissues as the steers remained longer in the feedlot and a higher percentage of total saturated fatty acids at 76 days than at the other two times. Quantitative separation of hepatic lipid classes by the Iatroscan revealed that phosphatidylcholine and phosphatidylethanolamine were the main components of the phospholipids. Presents as minor components were cardiolipin and sphingomyelin. No differences (P > 0..05) in these individual subclasses of liver lipids or in triglycerides were observed between the feedlot groups. Liver polyunsaturated fatty acids (PUFA) were higher (P < 0.001) at 104 than 76 days. In trial 2, steers fed a concentrate diet gained faster (P < 0.05) than the pasture group after 138 days. Marbling scores, yield grade, quality grade, fat over ribeye and per cent KPH were higher (P < 0.01) for the concentrate group while fat color scores were higher (P < 0.01) for the pasture group. Liver fatty acid analysis of summed omega6 PUFAs of triglyceride, phosphatidylcholine, phosphatidylethanolamine were higher for the feedlot than the pasture group. Linoleic acid was higher (P < 0.05) in the TG and PC liver subclass of the feedlot animals while higher (P < 0.05) linolenic acid occurred in the pasture group. PMID- 22054498 TI - Meat production characteristics of Egyptian Baladi and Angora goats. AB - Fifteen Baladi and 20 Angora intact males raised together from birth until 8 months of age were grown on a commercial concentrate mixture fed at the rate of 0.6 kg/head/day with chopped wheat straw fed at 0.5 kg/head/day for 14 weeks. Body measurements were taken before slaughter and carcass measurements and offal weights after it. The right sides of all carcasses were dissected into cuts, weighed and deboned. Fat was separated from the 9-10-11 rib joints and estimated. The two breeds did not significantly differ in birth weight, weaning weight, carcass weight, dressing percentage, most body measurements, all carcass measurements and most offal weights. Sigmificant differences were only found in body length, height at withers, weights of spleen and kidney fat. However, the Baladi had significant heavier loin and shoulder (P < 0.05) and breast and flank (P < 0.05) than the Angora which had heavier legs (P < 0.05). The carcasses of the two breeds had very similar percentage of edible meat (68.38 versus 68.65), lean (57.47 versus 57.38) and fat in the rib joint (10.91 versus 11.27). PMID- 22054499 TI - The non-sliding filaments of the sarcomere. AB - A model is proposed for the 'gap' or 'third' filaments of muscle, here renamed 'T filaments'. These consist of single titin molecules, spanning the half sarcomere from M-line to Z-line. Of several possibilities for stoichiometry and arrangement, the one most favoured here consists of six T-filaments lying longitudinally on the surface of the A-filament, one against each peripheral subfilament of myosin. C-protein molecules over-lie the T-filaments in transverse and axial rows, with their long axes following a helix. Each C-protein molecule helps to bind a pair of T-filaments to one A-strand (but not to bind A-strands together), and hinders the immune response of titin in the C-zone. The gap filaments arise from the coalescence of T-filaments in the I-band, and their extreme extensibility from an unravelling of a beaded structure in the titin molecule. A layout is presented for the molecule in zones of configuration and function. Possible arrangements of the T-filaments in the M- and N(2)-zones are discussed. PMID- 22054500 TI - Differentiation of raw meat from phylogenically related species by enzyme-linked immunosorbent assay. AB - A method, based on enzyme-linked immunosorbent assay (ELISA), has been developed for differentiating raw meat from closely related species of economic importance. By visual assessment 0.1% donkey in horse, 0.1% goat in sheep and 1% buffalo in beef may be detected. The technique is rapid and simple to perform and could be used in abattoirs and coldstores with results being available within 1 h. PMID- 22054501 TI - Effects of USDA feeder grade and time-on-feed on carcass characteristics and cooked beef palatability. AB - Yearling feeder steers (n = 128), selected to vary in frame size and muscle thickness, were fed for 100, 130 or 160 days and then slaughtered. USDA grade data were collected and cooked rib steaks were evaluated for palatability attributes. Frame size was positively related to carcass weight and longissimus muscle area and negatively related to all fatness measures and to USDA yield grade. Steaks from large-framed steers received the lowest sensory panel ratings for juiciness and overall palatability. Muscle thickness of feeder steers was positively related to all measures of carcass muscling. Steaks from thinly muscled (No. 3) steers received higher ratings for juiciness and overall palatability than did steaks from thickly muscled (No. 1) steers. Large-framed or thickly muscled (No. 1) steers produced the lowest percentages of carcasses with at least Choice quality. Although some statistically significant differences were observed when the data were sorted by frame size or muscle thickness, few real trends were evident that would be of value to cattle feeders. PMID- 22054502 TI - Investigation of the levels of N(tau)-Methylhistidine in a range of beef cuts and offals. AB - Protein-bound N(tau)-methylhistidine (N-MeHis) has been suggested as an index for the estimation of muscle (meat) protein in meat and meat products. This paper examines the levels of N-MeHis in a range of six prime beef cuts together with beef flank, cheek, mechanically recovered meat (MRM) and offals. The study was undertaken by two separate laboratories using a previously reported HPLC procedure involving the conversion of N-MeHis to a fluorescent derivative. It is shown that, whilst similar N-MeHis levels are present in the prime cuts, there is considerable variation in those found in the other cuts and offals. The average N MeHis level in six prime cuts observed at both laboratories is 122 MUg/g fat-free connective tissue-free (FFCF) meat; however, flank exhibits apparently high N MeHis levels, whilst cheek and MRM contain only approximately 70% of the level found in the prime cuts. The offals contain between 0 and 65% of the N-MeHis level found in prime cuts. The greater variability and the often lower value of the N-MeHis content of these legitimate meat materials preclude the establishment of a single realistic index for FFCF beef, and present fundamental problems for the assessment of the lean meat content of manufactured beef products by N-MeHis determination. PMID- 22054503 TI - Post-slaughter influences on the formation of metyyoglobin in beef muscles. AB - By the use of electrical stimulation and/or hot-boning and/or water baths adjusted to temperatures in the range 1-41 degrees C, beef muscles (Semimembranosus, Longissimus dorsi and Psoas major) were exposed to different pH/temperature/time regimes following slaughter and the formation of metmyoglobin (metMb) at their surfaces was monitored during subsequent aerobic storage at 1+/ 1 degrees C. The time course of formation was complex but, in general, consisted of an initial, rapid phase, lasting a few days, followed by a slower, or equilibrium, phase which ultimately yielded to a second rapid phase. Exposure to high temperature and low pH led to increased rates of metMb formation in the Longissimus dorsi and Semimembranosus muscles sliced 48 h after death but not in Psoas major muscles sliced 23 or 48 h post slaughter. However, ageing the Psoas major muscles, in vacuo, at 1 degrees C caused the high temperature treated samples to be less colour stable than those held at 1 degrees C. When the air stored samples were transferred to an anaerobic environment at 23.5 degrees C reduction of the metmyoglobin occurred, the rate of reduction being inversely proportional to the concentration of metMb developed during aerobic storage. It is suggested that the rate of metmyoglobin formation at the surface of beef muscle slices is dependent on at least two factors-the oxygen consumption rate (OCR) and the activity of an enzymic reducing system. In most practical circumstances the activity of the reducing system is the most important factor and this can be affected by the time, temperature and pH history of the muscle. PMID- 22054504 TI - Variations in the levels of 3-methyl-l-histidine of the myosins within the bovine carcass. AB - The 3-methyl-l-histidine levels were determined in the whole muscles from cheek, flank, round, neck and loin regions of the bovine carcass and in the corresponding myosins prepared from them. Titres were similar between the muscles in the latter three locations, but very low in cheek muscle. This finding was reflected by a very low titre for the myosin prepared from this source. PMID- 22054505 TI - Effect of salt and phosphate on the quality of Buffalo and Goat meats. AB - A study was conducted on the effect on certain quality parameters of adding sodium chloride (2.5%) and tetrasodium pyrophosphate (1%) to hot minced buffalo and goat meats. The effects on buffalo meat were observed in chilled and frozen conditions, those on goat meat in hot and chilled conditions. These treatments significantly increased pH, water-holding capacity (WHC) and emulsifying capacity (EC) and decreased cooking loss in both types of meat. Chilled and frozen conditions did not affect buffalo meat quality but salt additions to hot minced goat meat were superior to such additions to chilled minced meat in respect of EC and the extraction of salt-soluble proteins. Buffalo meat had poorer WHC and EC than goat meat and salt additions had a greater effect in improving EC. With goat meat, the treatment resulted in an increased WHC with a greater increase in pH. Significant correlations were observed among quality parameters. PMID- 22054506 TI - New algorithm for OHSS prevention. AB - Ovarian hyperstimulation syndrome (OHSS) still remains a life-threatening complication of in vitro fertilization treatment (IVF), keeping patients and especially those, who previously experienced OHSS, from attempting infertility treatment and childbearing. The recent implementation of four new modalities: the GnRH antagonist protocol, GnRH agonist (GnRHa) triggering of ovulation, blastocyst transfer and embryo/oocyte vitrification, renders feasible the elimination of OHSS in connection with ovarian hyperstimulation for IVF treatment. The proposed current algorithm is based on the number of follicles developed after ovarian stimulation, setting a cut-off level at the development of 18 or more follicles. Further, fulfilling this criterion, the algorithm is based on four decision-making points: the final day of patient work-up, the day of triggering final oocyte maturation, day-1 post oocyte pick-up (OPU) and day-5 post OPU. If the physician decides to administer hCG for final oocyte maturation regardless the type of analogue used, he has the option on day-1 to either freeze all embryos or to proceed to day-5. On this day, based on the clinical condition of the patient, a decision should be made to either transfer a single blastocyst or to vitrify all blastocysts available. However, this strategy will not guarantee an OHSS free luteal phase especially if a pregnancy occurs. If the physician decides to trigger ovulation with GnRHa, feasible only with the antagonist protocol, embryos can be cultured until day-5. On this day a transfer can be performed with no risk of OHSS and spare blastocysts may be vitrified. Alternatively, on day-1 or day-2 post OPU, all embryos could be frozen. Hopefully, in a near future, GnRHa triggering and vitrification of oocytes will become everyday practice. Only the combined use of a GnRH antagonist protocol with GnRHa triggering and subsequent single blastocyst transfer or embryo/oocyte freezing will completely abolish the risk of OHSS after ovarian hyperstimulation. PMID- 22054507 TI - Osteogenesis imperfecta missense mutations in collagen: structural consequences of a glycine to alanine replacement at a highly charged site. AB - Glycine is required as every third residue in the collagen triple helix, and a missense mutation leading to the replacement of even one Gly in the repeating (Gly-Xaa-Yaa)(n) sequence with a larger residue leads to a pathological condition. Gly to Ala missense mutations are highly underrepresented in osteogenesis imperfecta (OI) and other collagen diseases, suggesting that the smallest replacement residue, Ala, might cause the least structural perturbation and mildest clinical consequences. The relatively small number of Gly to Ala mutation sites that do lead to OI must have some unusual features, such as greater structural disruption because of local sequence environment or location at a biologically important site. Here, peptides are used to model a severe OI case in which a Gly to Ala mutation is found within a highly stabilizing Lys-Gly Asp sequence environment. Nuclear magnetic resonance, circular dichroism, and differential scanning calorimetry studies indicate this Gly to Ala replacement leads to a substantial loss of triple-helix stability and nonequivalence of the Ala residues in the three chains such that only one of the three Ala residues is capable of forming a good backbone hydrogen bond. Examination of reported OI Gly to Ala mutations suggests their preferential location at known collagen binding sites, and we propose that structural defects caused by Ala replacements may lead to pathology when they interfere with interactions. PMID- 22054508 TI - Educational difference in the prevalence of osteoporosis in postmenopausal women: a study in northern Iran. AB - BACKGROUND: Osteoporosis is the most common metabolic bone disease in the world and it is rapidly increasing in Iran. In this study the relationship between educational levels and osteoporosis was investigated among Iranian postmenopausal women. METHOD AND SUBJECTS: Seven hundred and six women aged 50-75 years old were randomly recruited from urban (n = 440) and rural (n = 266) areas in Guilan. Osteoporosis was diagnosed by quantitative ultrasound technique and dual X-ray absorptiometry. Serum 25(OH) D3, body weight and height were measured in all subjects. Other data including age, educational level, menopause age, medications and history of illness were also collected. RESULTS: We found that the prevalence of osteoporosis was significantly greater among women with low educational level than women with high educational status (18.0% vs 3.8% P < 0.0001). However, women with low educational level had higher mean serum level of vitamin D than women with high educational level. Osteoporosis was significantly more prevalent among women living in rural areas than women living in urban areas (19.1% v.s 13.3%, P < 0.0001). CONCLUSION: This study showed that educational level is associated with bone health in this population of postmenopausal women with significantly higher osteoporosis found in lower social groups. Therefore, we suggest that women with low social level should be carefully evaluated for signs of osteoporosis during routine physical examinations. PMID- 22054509 TI - Mechanisms of optimal defense patterns in Nicotiana attenuata: flowering attenuates herbivory-elicited ethylene and jasmonate signaling. AB - To defend themselves against herbivore attack, plants produce secondary metabolites, which are variously inducible and constitutively deployed, presumably to optimize their fitness benefits in light of their fitness costs. Three phytohormones, jasmonates (JA) and their active forms, the JA-isoleucine (JA-Ile) and ethylene (ET), are known to play central roles in the elicitation of induced defenses, but little is known about how this mediation changes over ontogeny. The Optimal Defense Theory (ODT) predicts changes in the costs and benefits of the different types of defenses and has been usefully extrapolated to their modes of deployment. Here we studied whether the herbivore-induced accumulation of JA, JA-Ile and ET changed over ontogeny in Nicotiana attenuata, a native tobacco in which inducible defenses are particularly well studied. Herbivore-elicited ET production changed dramatically during six developmental stages, from rosette through flowering, decreasing with the elongation of the first corollas during flower development. This decrease was largely recovered within a day after flower removal by decapitation. A similar pattern was found for the herbivore-induced accumulation of JA and JA-Ile. These results are consistent with ODT predictions and suggest that the last steps in floral development control the inducibility of at least three plant hormones, optimizing defense-growth tradeoffs. PMID- 22054510 TI - The effect of calcium carbonate and sodium alginate on the color and bind strength of restructured beef steaks. AB - This study investigated the effect of calcium carbonate concentration (0.00 0.26%) and sodium alginate concentration (0.0-1.4%) on the amount of discoloration and the raw and cooked bind-strength of restructured beef steaks. Alginate slightly increased and calcium carbonate markedly decreased the amount of discoloration in the restructured steaks. The protective effect of the calcium carbonate did not increase with increasing concentration and did not appear to be due to increased pH. The amount of discoloration in restructured steaks prepared with alginate was similar to that in conventionally prepared restructured steaks. The optimum concentration of calcium carbonate and alginate required for minimum discoloration and maximum raw and cooked bind-strength was 0.13% and 0.7%, respectively. PMID- 22054511 TI - Eating quality of meat from European * Chinese crossbred pigs. AB - Meat from half-Chinese crossbred pigs was compared with meat from purebred European pigs for chemical composition and eating quality. In a first experiment, purebred Pietrain pigs were compared to Pietrain * Chinese (Meishan or Jia Xin ) pigs for sensory qualities as assessed by a taste panel. In a second experiment, purebred Large Whites were compared to Large White * Meishan pigs for chemical composition and eating quality as assessed by both taste panel and consumer testing. The lipid and collagen content in the meat were higher in the Large White * Chinese crossbred pigs than in the purebred Large White pigs. In both experiments, meat from half-Chinese cross bred pigs was judged more tender, more juicy and more tasty than meat from purebred European pigs by the taste panel as well as by consumers. However, the latter judged that the overall acceptability of the meat from half-Chinese pigs was not better, probably due to the excessive amount of visible fat. PMID- 22054512 TI - Effect of added water, sodium erythorbate and storage time on the functional properties of prerigor beef preblends in a model system. AB - Singular and combined effects of added water, sodium erythorbate and storage time on salt soluble protein extractability, bacteriological and chemical characteristics of preblended hot-boned beef were evaluated. Waterholding and gel forming capacities of preblended hot-boned beef containing either 0, 10 or 20% added water were determined. Significant interactions between added water level and storage time on microbial counts and between sodium erythorbate level and storage time on thiobarbituric acid values and residual nitrite levels were noted. The presence of sodium erythorbate resulted in a more (P < 0.05) rapid rate of nitrite disappearance, but it did not affect (P > 0.05) microbial counts. Salt-soluble protein extractability was not affected (P > 0.05) by added water, but more protein could be extracted with increasing storage time. A trend existed to suggest that the presence of added water in the meat preblends slightly improved the gel formation and waterholding capacities. PMID- 22054513 TI - Production and characterization of monoclonal antibodies specific to chicken muscle soluble proteins. AB - Three stable hybridoma cell lines (AH4, BC9 and CF2) have been produced which secrete monoclonal antibodies specific for chicken and turkey muscle proteins. Partial characterization by ELISA and SDS-PAGE immunoblotting indicated that the antibodies failed to cross-react with similar extracts of pork, beef, lamb, horse or rabbit. One of the cell lines (AH4) secreted a monoclonal antibody that was also capable of distinguishing between chicken and turkey by indirect ELISA. PMID- 22054514 TI - Catalysts of lipid oxidation in meat products. AB - In emulsions consisting of refined lard, egg white and corn starch haemoglobin, initially a mixture of the oxy and met forms, at levels similar to the haemoprotein contents found in fresh meat, was a far more powerful catalyst of lipid oxidation, as measured by TBA number, than inorganic iron compounds at levels appropriate to those found in meat. This was true over the pH range 4.5 to 7.5. When added and evenly distributed to exhaustively washed muscle fibres (WF), at levels appropriate to those found in meat, haemoglobin was again a powerful catalyst, but all forms of inorganic iron appeared to have little prooxidant activity. The rate of oxidation of the lipid was very dependent on the haemoprotein concentration, being maximal in the range 10(-4) to 10(-5) M. This equates to an approximate unsaturated lipid to haem molar ratio of several hundred to one, similar to the values reported for model linoleate haem systems. In heated systems the haemoprotein again appeared to be a more effective catalyst than inorganic iron at levels appropriate to those found in meat. It is concluded that the conflicting results as to the roles of haem pigments and inorganic iron in lipid oxidation found in the literature are due, at least in part, to the difficulty of evenly dispersing the catalysts in the washed fibres, especially if heat or freezing leads to subsequent phase separation, and that H(2)O(2), formed by autoxidation of the oxypigments, may be necessary for ferric haem pigments to be effective catalysts. PMID- 22054515 TI - Iron absorption from meat and meat products: Part I-Theoretical foundations for estimating available iron. AB - A theoretical foundation is developed to estimate available meat iron. Iron absorption factors are calculated for various kinds of raw meat. A methodology for estimating available iron from finished meat products, depending on the content of different meat ingredients, is suggested. PMID- 22054516 TI - Iron absorption from meat and meat products: Part 2-Iron absorption from high roughage meat products. AB - The main reasons for the inhibiting effect of dietary fibre on meat iron absorption in the intestine are examined. A model experiment estimates binding of iron by the dietary fibre (DF) of wheat bran. A radioactive tracer method was applied to volunteers to detect the availability of iron from fibrous meat foods. The evidence suggests that incorporating up to 2% of dietary fibre into meat products reduces iron absorption factors by no more than 1-2%. Adding ascorbic acid in the presence of DF lowers them only by 0.1-0.5%, i.e. it does not damage iron absorption processes. PMID- 22054519 TI - [Decreasing incidence of stent thrombosis]. AB - Stent thrombosis (ST) remains a major pitfall of stent implantation in contemporary percutaneous coronary intervention (PCI) leading to high rates of death and non-fatal myocardial infarction. Many predictors of ST have been reported worldwide but the strongest have to be highlighted regarding the catastrophic prognosis of such an event. Because platelet aggregation has a pivotal role in ST pathogenesis, the new antiplatelet regimens combining aspirin and P2Y12 receptor inhibitors have led to a remarkable decrease in the ST incidence, especially in the setting of acute coronary syndrome (ACS). In this article, our purpose is to review the evolution of ST incidence since first stent use in PCI. We will also overview the main predictors of ST focusing on ACS and clopidogrel low response. PMID- 22054520 TI - Retaining clients in an outcome monitoring evaluation study: HIV prevention efforts in community settings. AB - The Centers for Disease Control and Prevention (CDC), Division of HIV/AIDS Prevention (DHAP) conducted outcome monitoring studies on evidence-based interventions (EBIs) provided by CDC-funded community-based organizations (CBOs). Critical to the success of outcome monitoring was the ability of CBOs to recruit and retain clients in evaluation studies. Two EBIs, Video Opportunities for Innovative Condom Education and Safer Sex (VOICES/VOCES) and Healthy Relationships, were evaluated using repeated measure studies, which require robust follow-up retention rates to increase the validity and usefulness of the findings. The retention rates were high for both VOICES/VOCES CBOs (95.8% at 30 days and 91.1% at 120 days), and Healthy Relationships CBOs (89.5% at 90 days and 83.5% at 180 days). This paper presents an overview of the retention of clients, challenges to follow-up, and strategies developed by CBOs to achieve high retention rates. These strategies and rates are discussed within the context of the CBOs' target populations and communities. PMID- 22054521 TI - Using GIS to enhance programs serving emancipated youth leaving foster care. AB - This article describes a GIS prototype designed to assist with the identification and evaluation of housing that is affordable, safe, and effective in supporting the educational goals and parental status of youth transitioning from foster care following emancipation. Spatial analysis was used to identify rental properties based on three inclusion criteria (affordability, proximity to public transportation, and proximity to grocery stores), three exclusion criteria (areas of high crime, prostitution, and sexual predator residence), and three suitability criteria (proximity to health care, mental health care, and youth serving organizations). The results were applied to four different scenarios to test the utility of the model. Of the 145 affordable rental properties, 27 met the criteria for safe and effective housing. Of these, 19 were located near bus routes with direct service to post-secondary education or vocational training programs. Only 6 were considered appropriate to meet the needs of youth who had children of their own. These outcomes highlight the complexities faced by youth when they attempt to find affordable and suitable housing following emancipation. The LEASE prototype demonstrates that spatial analysis can be a useful tool to assist with planning services for youth making the transition to independent living. PMID- 22054522 TI - Analysing the effect of public health campaigns on reducing excess weight: a modelling approach for the Spanish Autonomous Region of the Community of Valencia. AB - Excess weight is fast becoming a serious health concern in the developed and developing world. The concern of the public health sector has lead to the development of public health campaigns, focusing on two-fold goals: to inform the public as to the health risks inherent in being overweight, and the benefits of a change in nutritional behaviour. Recent studies indicate that the effects of the average public health campaign on the target community is around 5%. In this study we aim to quantify the effect of different public health campaigns on lifestyle behaviour in the target populations in order to bring about weightloss in a significant number of people over the next few years. This study is based on recent works that consider excess weight as a consequence of the transmission of unhealthy lifestyles from one individual to another. Following this point of view, first a mathematical model is presented. Then, policies based on public health campaigns addressed to stop people gaining weight (prevention; this type of policy acts on individuals in order to maintain their weight and to stop an increase in weight) and, policies addressed to overweight individuals to reduce their weight (treatment; these campaigns act on overweight and/or obese individuals in order to reduce their weight) are simulated in order to evaluate their effectiveness. The study concludes that combination of preventive plus treatment campaigns are more effective than considering them separately. PMID- 22054523 TI - Evaluation of the Neurodegenerative Conditions Coordinated Care Program (NCCCP) in Western Australia: barriers to better service provision. AB - This paper details a 2009-2010 evaluation of the Neurodegenerative Conditions Coordinated Care Program (NCCCP) commissioned by the Disability Services Commission (DSC) in Western Australia (WA). The program, run by the Multiple Sclerosis Society of WA (Inc.) provides in-home care and supports and respite for people who are under the age of sixty-five and diagnosed with a rapidly degenerative neurological condition. In 2009, the identified barriers to the better provision of services included: shortage of quality out-of-home respite providers, and convoluted paperwork requirements to qualify for the program. Some service providers were unaware of the program and so were not referring them into the NCCCP, a number of service providers were unwilling to refer their clients into the program, neurologists were unwilling to give a final diagnosis for a client, that would enable them to qualify for the service, there was a general lack of knowledge about what services were available in the general community, and existing equipment pools were under-resourced. In 2010, the study found that most of the issues had been addressed however, out-of-home respite services were still very limited especially in rural areas, and the eligibility criteria for entry to the program is confined to those 65 years and under. This paper discusses the issues that still remain with the program as examples of barriers to better provision of services. PMID- 22054524 TI - Benefits and costs associated with mutual-help community-based recovery homes: The Oxford House model. AB - We used data from a randomized controlled study of Oxford House (OH), a self-run, self-supporting recovery home, to conduct a cost-benefit analysis of the program. Following substance abuse treatment, individuals that were assigned to an OH condition (n=68) were compared to individuals assigned to a usual care condition (n=61). Economic cost measures were derived from length of stay at an Oxford House residence, and derived from self-reported measures of inpatient and outpatient treatment utilization. Economic benefit measures were derived from self-reported information on monthly income, days participating in illegal activities, binary responses of alcohol and drug use, and incarceration. Results suggest that OH compared quite favorably to usual care: the net benefit of an OH stay was estimated to be roughly $29,000 per person on average. Bootstrapped standard errors suggested that the net benefit was statistically significant. Costs were incrementally higher under OH, but the benefits in terms of reduced illegal activity, incarceration and substance use substantially outweighed the costs. The positive net benefit for Oxford House is primarily driven by a large difference in illegal activity between OH and usual care participants. Using sensitivity analyses, under more conservative assumptions we still arrived at a net benefit favorable to OH of $17,830 per person. PMID- 22054525 TI - Process evaluation of a diversity training program: the value of a mixed method strategy. AB - Patients' health and health needs are influenced by categories of difference like sex, gender, ethnic origin and socioeconomic status (SES). To enhance awareness of this diversity among patients and to provide holistic care for them, health professionals should first be aware of the relation between dimensions of diversity and patients' health and health demands. This paper presents a formative process evaluation of a diversity sensitivity training programme for healthcare professionals. The training was implemented in three healthcare settings (mental healthcare, nursing home and hospital care). Mixed methods were used to monitor the implementation of the training and its effects after three years. Findings demonstrate that the training stimulated participants' awareness, knowledge and critical attitudes towards diversity. Their motivation and willingness to take action regarding diversity was also enhanced. Yet these developments were less apparent among nursing home participants who felt less satisfied and did not develop a critical perspective on this issue. Qualitative data were helpful to explain differences between the settings. By means of the combination of quantitative and qualitative data, we can conclude that individual learning was not enough to guarantee a sensitive approach to diversity at the organizational level. PMID- 22054526 TI - Assessing state substance abuse prevention infrastructure through the lens of CSAP's Strategic Prevention Framework. AB - Although the organizational structures and operating procedures of state substance abuse prevention systems vary substantially across states, there is scant empirical research regarding approaches for rigorous assessment of system attributes and which attributes are most conducive to overall effectiveness. As one component of the national cross-site evaluation of the SPF State Incentive Grant Program (SPF SIG), an instrument was developed to assess state substance abuse prevention system infrastructure in order to measure infrastructure change and examine the role of state infrastructure in achieving prevention-related outcomes. In this paper we describe the development of this instrument and summarize findings from its baseline administration. As expected, states and territories were found to vary substantially with respect seven key characteristics, or domains, of state prevention infrastructure. Across the six domains that were assessed using numeric ratings, states scored highest on data systems and lowest on strategic planning. Positive intercorrelations were observed among these domains, indicating that states with high capacity on one domain generally have relatively high capacity on other domains as well. The findings also suggest that state prevention infrastructure development is linked to both funding from state government and the presence of a state interagency coordinating body with decision-making authority. The methodology and baseline findings presented will be used to inform the ongoing national cross-site evaluation of the SPF SIG and may provide useful information to guide further research on state substance abuse prevention infrastructure. PMID- 22054527 TI - Designing and implementing an evaluation of a national work support program. AB - Welfare reforms in the 1990s have shifted governments around the world towards financial assistance conditional on work. While large-scale rigorous research on welfare-to-work programs has demonstrated effectiveness towards employment in other countries, no such micro-level evaluation of a policy has ever been conducted in Singapore. This article describes the process of developing a large experimental evaluation of the Work Support Program, which the Ministry of Community Development, Youth and Sports started in 2006. The lessons learned from planning and implementing the research can be helpful to future researchers in negotiating long-term rigorous evaluations in an environment where collaborators lack sufficient research knowledge. Insights include ways to focus on the essentials, find alternative experimental designs, collaborate effectively, and adapt instruments across cultures. PMID- 22054528 TI - Process evaluation of an environmental walking and healthy eating pilot in small rural worksites. AB - Small Steps are Easier Together (SS) was a pilot environmental intervention in small rural worksites in Upstate New York in collaboration with Extension educators. Worksite leaders teamed with co-workers to select and implement environmental changes to increase walking steps over individual baseline and to choose healthy eating options over 10 weeks. Participants were 226 primarily white, women employees in 5 sites. A mixed methods process evaluation, conducted to identify determinants of intervention effectiveness and to explain differences in outcomes across worksites, included surveys, self-reports of walking and eating, interviews, focus groups, and an intervention log. The evaluation assessed reach, characteristics of recruited participants, dose delivered, dose received, and context and compared sites on walking and eating outcomes. Emergent elements of participant-reported dose received included: active leadership, visible environmental changes, critical mass of participants, public display of accomplishments, accountability to co-workers, and group decision making. Participants at sites with high reach and dose were significantly more likely than sites with low reach and dose to achieve intervention goals. Although this small pilot needs replication, these findings describe how these evaluation methods can be applied and analyzed in an environmental intervention and provide information on trends in the data. PMID- 22054529 TI - Relational responsibilities in responsive evaluation. AB - This article explores how we can enhance our understanding of the moral responsibilities in daily, plural practices of responsive evaluation. It introduces an interpretive framework for understanding the moral aspects of evaluation practice. The framework supports responsive evaluators to better understand and handle their moral responsibilities. A case is introduced to illustrate our argument. Responsive evaluation contributes to the design and implementation of policy by working with stakeholders and coordinating the evaluation process as a relationally responsible practice. Responsive evaluation entails a democratic process in which the evaluator fosters and enters a partnership with stakeholders. The responsibilities of an evaluator generally involve issues such as 'confidentiality', 'accountability' and 'privacy'. The responsive evaluator has specific responsibilities, for example to include stakeholders and vulnerable groups and to foster an ongoing dialogue. In addition, responsive evaluation involves a relational responsibility, which becomes present in daily situations in which stakeholders express expectations and voice demands. In our everyday work as evaluators, it is difficult to respond to all these demands at the same time. In addition, this article demonstrates that novice evaluators experience challenges concerning over- and underidenfitication with stakeholders. Guidelines and quality criteria on how to act are helpful, but need interpretation and application to the unique situation at hand. PMID- 22054530 TI - Using agency data for evidence-based programming: a university-agency collaboration. AB - Agencies providing residential treatment are encouraged, or even mandated, to collect outcomes data and to implement evidence based practices, yet little guidance has been provided on how to do so using agency administrative data that are collected on an ongoing basis. We examined data on Child and Adolescent Functional Assessment Scale (CAFAS) scores for 1608 admissions to a residential treatment center from 2002 through 2008. CAFAS scores were measured every 90 days, providing multiple CAFAS scores for each individual. Results demonstrated that on average residents improved in functioning over time. Sensitive to the evolving needs of residents who had been entering the program, the treatment center made significant program changes in 2006 to attempt to better serve residents through a broad array of specialized programming. Compared to the overall results, the analysis suggested that residents who entered the program since October 2006 appeared to have made larger improvements in their CAFAS scores. Results were derived by employing multilevel models appropriate for estimating growth trajectories with repeated measures data. Conversations with agency staff suggested that using administrative data, and advanced statistical models, were extremely helpful for organizational decision making and evidence based programming. PMID- 22054532 TI - Understanding the "what should be condition" in needs assessment data. AB - In needs assessment (N/A), the calculation of discrepancies is based on the assumption the "what should be" condition is a reasonable representation of respondent perceptions. That assumption may be erroneous and requires a closer inspection. This paper examines the use of importance scores in NA and some of the problems that can arise when they are used as a proxy to measure the "what should be" condition. A review of the literature and ways of dealing with importance scores are presented, followed by a discussion of the problems and issues that can arise. Some solution strategies are offered along with recommendations for practice and research. The paper provides guidance for others interested in improving needs assessment procedures. PMID- 22054533 TI - Evaluation of a system designed to link people living with HIV/AIDS with mental health services at an AIDS-service organization. AB - This study evaluated the Rapid Response System, an initiative designed to link people living with HIV/AIDS with mental health services at an AIDS service organization. Data were extracted from agency records for 314 clients who had contact with the Rapid Response System over a 6-month period. Of the 281 clients who scheduled an appointment for an evaluation to initiate mental health services, 64% completed the evaluation. In the multivariate analysis, Latinos were significantly less likely than whites to complete the mental health evaluation. Further, there was a significant decrease in the likelihood of completing the mental health evaluation as the number of days between the Rapid Response System contact and the date of the evaluation appointment increased. Strategies that reduce the period of time between the initial referral and initiation of services may facilitate linkage with mental health treatment, particularly in the context of larger multi-service organizations. PMID- 22054531 TI - A community prevention model to prevent children from inhaling and ingesting harmful legal products. AB - Children's misuse of harmful legal products (HLPs), including inhaling or ingesting everyday household products, prescription drugs, and over-the-counter drugs, constitutes a serious health problem for American society. This article presents a community prevention model (CPM) focusing on this problem among pre and early adolescents. The model, consisting of a community mobilization strategy and environmental strategies targeting homes, schools, and retail outlets, is designed to increase community readiness and reduce the availability of HLPs, which is hypothesized to reduce HLPs use among children. The CPM is being tested in Alaskan rural communities as part of an inprogress eight-year National Institute on Drug Abuse randomized-controlled trial. This paper presents the CPM conceptual framework, describes the model, and highlights community participation, challenges, and lessons learned from implementation of the model over a 21-month period. PMID- 22054534 TI - Survey of enterovirus infections from hand, foot and mouth disease outbreak in China, 2009. AB - BACKGROUND: In China, a rapid expansion of Hand, foot, and mouth disease (HFMD) outbreaks has occurred since 2004 and HFMD has become an important issue for China. However, people are still only concerned with human enterovirus 71(HEV-71) and coxsackie virus A16 (CV-A16). Much of what is known about the other enterovirus infections relies on fractional evidence and old epidemic data, with little knowledge concerning their distribution. To alert potential threatens of the other enteroviruses, our study genetically characterized specimens from different regions of China and yielded novel information concerning the circulating and phylogenetic characteristics of enteroviral strains from HFMD cases. FINDINGS: A total of 301 clinical throat swabs were randomly obtained from patients suffering from HFMD from the southern, northern and central regions of China during outbreaks in 2009. 266 of 301 (88.4%) HFMD cases were found positive for HEV and seven genotypes, HEV-71, CV-A16, -B5, -A4, -A6, -A10, and -A12, were detected. CONCLUSIONS: The HFMD pathogen compositions in the different regions of China were significantly different. HFMD epidemics might persist for a long time in China due to the multiple pathogen compositions, the enteroviral characteristic of recombination and co-infection, the ever-increasing travel and migration and the deficiency of effective vaccine. Our study deserves the attention on HFMD control and vaccine development. PMID- 22054535 TI - In situ formation and collagen-alginate composite encapsulation of pancreatic islet spheroids. AB - In this study, we suggest in situ islet spheroid formation and encapsulation on a single platform without replating as a method for producing mono-disperse spheroids and minimizing damage to spheroids during encapsulation. Using this approach, the size of spheroid can be controlled by modulating the size of the concave well. Here, we used 300 MUm concave wells to reduce spheroid size and thereby eliminating the central necrosis caused by large volume. As the encapsulation material, we used alginate and collagen-alginate composite (CAC), and evaluated their suitability through diverse in vitro tests, including measurements of viability, oxygen consumption rate (OCR), hypoxic damage to encapsulated spheroids, and insulin secretion. For in situ encapsulation, alginate or CAC was spread over a concave microwell array containing spheroids, and CaCl(2) solution was diffused through a nano-porous dialysis membrane to achieve uniform polymerization, forming convex structures. By this process, the formation of uniform-size islet spheroids and their encapsulation without an intervening replating step was successfully performed. As a control, intact islets were evaluated concurrently. The in vitro test demonstrated excellent performance of CAC-encapsulated spheroids, and on the basis of these results, we transplanted the islet spheroids-encapsulated with CAC into the intraperitoneal cavity of mice with induced diabetes for 4 weeks, and evaluated subsequent glucose control. Intact islets were also transplanted as control to investigate the effect of encapsulation. Transplanted CAC-encapsulated islet spheroids maintained glucose levels below 200 mg/dL for 4 weeks, at which they were still active. At the end of the implantation experiment, we carried out intraperitoneal glucose tolerance test (IPGTT) in mice to investigate whether the implanted islets remained responsive to glucose. The glucose level in mice with CAC encapsulated islet spheroids dropped below 200 mg/dL 60 min after glucose injection and was stably maintained. In conclusion, the proposed encapsulation method enhances the viability and function of islet spheroids, and protects these spheroids from immune attack. PMID- 22054536 TI - The use of air-flow impedance to control fiber deposition patterns during electrospinning. AB - Electrospun non-woven structures have the potential to form bioresorbable vascular grafts that promote tissue regeneration in situ as they degrade and are replaced by autologous tissue. Current bioresorbable grafts lack appropriate regeneration potential since they do not have optimal architecture, and their fabrication must be altered by the manipulation of process parameters, especially enhancing porosity. We describe here an air-impedance process where the solid mandrel is replaced with a porous mandrel that has pressurized air exiting the pores to impede fiber deposition. The mandrel design, in terms of air-flow rate, pore size, and pore distribution, allows for control over fiber deposition and scaffold porosity, giving greater cell penetration without a detrimental loss of mechanical properties or structural integrity. PMID- 22054537 TI - Primary acute omental torsion in an overweight girl. PMID- 22054538 TI - The many challenges of open access. PMID- 22054541 TI - Antibodies 2.0. PMID- 22054542 TI - Cloning efficiency. PMID- 22054543 TI - Advancing the state of the art. Interview by Kristie Nybo. PMID- 22054545 TI - [Letter to the editor] Ethylene emitted by nylon membrane filters questions their usefulness to transfer plant seedlings between media. PMID- 22054544 TI - Modern fluorescent proteins: from chromophore formation to novel intracellular applications. AB - The diverse biochemical and photophysical properties of fluorescent proteins (FPs) have enabled the generation of a growing palette of colors, providing unique opportunities for their use in a variety of modern biology applications. Modulation of these FP characteristics is achieved through diversity in both the structure of the chromophore as well as the contacts between the chromophore and the surrounding protein barrel. Here we review our current knowledge of blue, green, and red chromophore formation in permanently emitting FPs, photoactivatable FPs, and fluorescent timers. Progress in understanding the interplay between FP structure and function has allowed the engineering of FPs with many desirable features, and enabled recent advances in microscopy techniques such as super-resolution imaging of single molecules, imaging of protein dynamics, photochromic FRET, deep-tissue imaging, and multicolor two photon microscopy in live animals. PMID- 22054546 TI - Purification of BAC DNA for high-efficiency transgenesis. AB - An unresolved bottleneck in bacterial artificial chromosome (BAC) transgenesis is low efficiency generation of founder mice because of suboptimal quality of the manipulated BAC DNA. Using mini-gel electrophoresis and electro-elution that circumvents CsCl(2) centrifugation, column chromatography, and resin purifications, we have used RECOCHIP, a commercially available dialysis cassette for the purification of BAC DNA that generates transgenic founders with up to 80% efficiency. PMID- 22054547 TI - Isolation of Sertoli, Leydig, and spermatogenic cells from the mouse testis. AB - A thorough understanding of the events during mammalian spermatogenesis requires studying specific molecular signatures of individual testicular cell populations as well as their interaction in co-cultures. However, most purification techniques to isolate specific testicular cell populations are time-consuming, require large numbers of animals, and/or are only able to isolate a few cell types. Here we describe a cost-effective and timesaving approach that uses a single protocol to enrich multiple testicular cell populations (Sertoli, Leydig, and several spermatogenic cell populations) from as few as one mouse. Our protocol combines rigorous enzymatic digestion of seminiferous tubules with counter-current centrifugal elutriation, yielding specific testicular cell populations with >80%-95% purity. PMID- 22054548 TI - FlyCounter: a simple software for counting large populations of small clumped objects in the laboratory. AB - While several software programs exist to count bacterial colonies on a Petri plate, no suitable solution is available for quick and reliable enumeration of small, live insects. We have written a program called FlyCounter that can obtain counts from images, even if insects are highly clumped in space. We also describe a simple and inexpensive system for anesthetizing and capturing high-quality images of the small insects. Taken together, our process is fast, fully automatic, and has a low percentage of error (~1%-4% on average). Although we have tested our software on fruit flies, it should be simple to extend to other organisms of similar size. PMID- 22054549 TI - Environmental and epidemiological surveillance of Vibrio cholerae in a cholera endemic region in India with freshwater environs. AB - AIM: To conduct epidemiological and ecological surveillance of cholera in freshwater environments. METHODS AND RESULTS: A freshwater region of India was surveyed between April 2007 and December 2008. Vibrio cholerae was isolated from 59.5% of water and plankton samples (n = 357) and 35.5% of stool samples (n = 290). Isolation from water was dependent on air (r = 0.44) and water temperatures (r = 0.49) (P < 0.01) but was independent of rainfall (r = 0.15), chlorophyll a (r = 0.18), salinity (r = 0.2) or pH (r = 0.2) (P > 0.05). Isolation from plankton was dependent on temperature of air (r = 0.45), water temperature (r = 0.44), chlorophyll a concentration (r = 0.42), pH (r = 0.23) and salinity (r = 0.39) (P < 0.01). Cholera cases correlated with rainfall (r = 0.82, P < 0.01) and chlorophyll a concentration (r = 0.42, P < 0.05), but not with air temperature (r = 0.3, P = 0.37). Vibrio cholerae O1 possessed ctxB, ctxA, rstR and tcpA (ElTor), toxR, toxT, rtxA, rtxC, mshA and hylA. Among non-O1-non-O139, the distribution of virulence-associated and regulatory protein genes was heterogeneous with - 0.7, 2.2, 94.77, 97.76, 99.25, 100 and 100% isolates being positive for tcpA, toxT, rtxA, rtxC, hylA, toxR and mshA, respectively. Two-thirds of non-O1-non-O139 isolates exhibited antibiotic resistance to various antibiotics that did not correlate with geographical site or time of origin for the isolates. RAPD and AFLP showed V. cholerae to be a diverse bacterium. AFLP demonstrated separate lineages for non-O1-non-O139 and O1 isolates. CONCLUSION: Environmental parameters played a significant role in the emergence and spread of cholera and the abundance of V. cholerae. But based on virulence gene profiling and genetic fingerprinting, the possibility of origin of toxigenic isolates from nontoxigenic environmental isolates seems unlikely in freshwater environs of India. SIGNIFICANCE AND IMPACT OF THE STUDY: This study explains the ecology, epidemiology and seasonality of cholera in freshwater environs. PMID- 22054550 TI - Meat tenderness and the gap filaments. AB - A theory is developed relating the myofibrillar component of meat tenderness to a third set of filaments in the sarcomere: the 'gap filaments'. It is prooposed that the gap filaments set the limit to the tensile strength of the raw or heat denatured myofibril. The basic process of ageing appears to be an attack by 'calcium-activated factor' (CAF) on the integrity of these filaments. An attempt is made to give an integrated picture of the role of both gap filaments and connective tissue in determining the tensile properties of raw, lightly cooked and well cooked meat. PMID- 22054551 TI - Comparison of carcase yield, carcase composition and quality characteristics of buffalo meat and beef. AB - The yield of carcase and by-products was found to be only slightly different between buffaloes and non-improved (Busha) cattle of comparable age, feeding treatment and sex. The percentage of separable fat was slightly higher, and that of bone slightly lower, in the buffaloes. In comparing the meat from buffalo and Simmental cattle of the same age and finish, a rather higher protein content was found in the former, but this reflected a somewhat higher concentration of connective tissue in the buffalo meat. The diameter of muscle fibres in buffalo tended to be less than that of corresponding muscle in Simmental cattle (except in M. Supraspinatus of cows). These findings suggest that buffalo meat is no coarser than beef when valid comparisons are made. PMID- 22054552 TI - Note on the effect of ageing on the neutral salt and acid soluble collagen from the intramuscular connective tissue of various species. AB - The neutral salt soluble (NSSC) and acid soluble collagens (ASC) from the intramuscular connective tissue of various species were extracted, purified and studied by optical rotatory dispersion, viscosity and polyacrylamide gel electrophoresis. No significant changes in the quantity of such soluble fractions, in the optical rotatory dispersion or in viscosity of the purified samples were observed during two weeks storage at 1 degrees C. Electrophoretical analysis suggested a decrease in the relative concentration of the alpha chains of the ASC. It was concluded that if there are changes in the NSSC or ASC of muscle during ageing these are not detected by the techniques employed. PMID- 22054553 TI - Lamb and mutton flavour: Contributing factors and chemical aspects. AB - A review of the occurrence and chemistry of lamb/mutton flavour is presented. The low consumption of both lamb and mutton has been attributed to the flavour of these meats. There is general agreement that the flavour of meat from younger animals is more desirable than that from older ones. Further, the flavour intensity of meat from wethers is less than that of ewes, less than rams. Breed appears to have an effect; mutton flavour is more predominant in the fine-wool breeds and is apparently directly related to the fineness of the wool. However, no significant sire effects within or between breeds have been reported. Nutritional factors appear to play a major role in the flavour intensity of sheep meat. Certain foodstuffs (legumes and grains) can intensify the flavour, whereas withdrawal of sheep from grazing before slaughter can reduce it. There is no reliable evidence to implicate slaughtering and processing factors (except heating) in flavour development. although the exact chemical compounds responsible for lamb/mutton flavour are not yet known, they are undoubtedly lipid soluble, with the carbonyl and/or sulphur-containing compounds as the most promising candidates. Further, there appears to be no consistent expression of a 'characteristic' lamb/mutton flavour. PMID- 22054554 TI - Molecular weight distribution of soluble polypeptides from the 'Parma county ham' before, during and after maturation. AB - SDS polyacrylamide gel electrophoresis has been employed to study the molecular weight distribution of soluble polypeptides from the 'Parma county ham', a salted pork product. Limited proteolysis was observed, but this was mainly confined to the sarcoplasmic proteins. The results are discussed in the light of previous studies on the same type of products. PMID- 22054555 TI - The influence of the collagen fibre network of muscle on the compliance and tensile strength of muscle samples subjected to loads at right angles to the muscle fibre axis. AB - The pattern of subdivision of a muscle into fibre bundles by the perimysium was examined as a possible source of within sample variability of meat toughness attributable to the connective tissue component. It was shown that the pattern of subdivision into fibre bundles relates to the tendom surfaces and influences the compliance and toughness of a meat sample. In addition it was shown that greater plasticity of raw meat samples results in greater compliance under load. The procedure of defining sample orientation relative to the geometry of the component parts enables some of the within sample variability to be explained and controlled. PMID- 22054556 TI - Relative role of catalysts and reductants in the formation of metmyoglobin in aerobically stored beef. AB - The formation of metmyoglobin (metMb) in sterile minced and intact slices of beef has been determined during storage at 1 degrees C. The oxidation of oxymyoglobin in minced beef is first order, the rate constants for different muscles, although being pH dependent, are similar for all the muscles studied. The rate is about four or five times faster than that reported for oxymyoglobin in solution, indicating that catalysis occurs. In intact slices the reaction profile is more complex as a pseudoequilibrium level of metmyoglobin forms after a few days at 1 degrees C, the concentration of metMb remaining constant for several days and then being followed by further rapid oxidation to 100% metMb. Due to variations in an aerobic reducing system present in intact beef the duration of the pseudoequilibrium varies markedly from muscle to muscle; this reducing system is destroyed by mincing. The rate of metMb formation in intact muscles varies with sample shape, thin slices being more colour stable ones. Reasons for this dependence on sample shape are discussed. PMID- 22054557 TI - Freezing rate, frozen storage and lamb tenderness. PMID- 22054558 TI - Identification of PSE in the Longissimus muscle of pigs stunned by captive-bolt. AB - Meat quality characteristics in the longissimus muscle of 57 pigs slaughtered at approximately 100 kg liveweight were studied. They were slaughtered by captive bolt stunning and exsanguination. The incidence of pale, soft and exudative (PSE) meat was identified by muscle colour and water holding capacity 24 h post mortem (C(24) and WHC(24)). The muscle pH value 45 min post mortem (pH(1)), absorption ratio (R-value) of muscle acid extract, and colour and water holding capacity 1 h post mortem (C(1) and WHC(1)) were also determined. The interrelationships among pH(1), R-value, C(1), WHC(1), C(24) and WHC(24) were studied and the multiple regressions of C(1), C(24), WHC(1) and WHC(24) with pH(1) and R-value were computed. The results of simple and multiple regression analysis showed that neither muscle pH(1) nor R-value could effectively predict colour or WHC at 24 h post mortem. Combining pH(1) and R-value provided little improvement in the prediction of the ultimate meat colour and WHC. PMID- 22054559 TI - Effect of sex grouping during growth on 5alpha-androstenone development in boars at three commercial slaughter weights. AB - Groups of boars and gilts were grown in either single-sex or mixed groups to slaughter weights of 81, 93 or 110 kg liveweight to examine the effects of sex grouping on growth performance, animal behaviour and the development of androstenone-taint in the males. Results confirmed the well known growth advantages of entire males and showed that no husbandry problems of any significance were incurred with the boars and gilts raised together, particularly in those groups slaughtered before reaching 100 kg liveweight. In pigs taken to heavier weights, boars were successfully reared with gilts without incurring management problems, although growth performance was slightly poorer for the boar/gilt groups compared with mixed castrates and gilts, and some of the boars had high concentrations of androstenone in the fat. Thus, for pigs intended for slaughter at heavy commercial weight, the evidence suggests that split-sex rearing (and therefore feeding) should be practised. No useful correlations of androstenone concentration in fat were found with thickness of backfat, age, carcass weight or liveweight at slaughter. PMID- 22054560 TI - Structural changes developing with rigor that facilitate bacterial invasion of muscle tissue. AB - Pre-rigor skeletal muscle fibres shrank in hypertonic and swelled in hypotonic fixative solutions, but the radial dimensions of post-rigor muscle fibres did not change with variations in the effective osmolalities of fixative solutions. Muscle fibres apparently undergo radial shrinkage during the development of rigor and, in so doing, can pull away from their surrounding endomysia. The resulting gaps between post-rigor muscle fibres and endomysia probably contain muscle cell cytoplasm. Bacteria penetrate muscle tissue via these gap regions. PMID- 22054561 TI - Muscle sample preparation for scanning electron microscopy. AB - Scanning electron microscopy has a number of features which make it more suited to studying the relationships between muscle structure and the rheological properties of meat than either light microscopy or transmission electron microscopy. One of these features is the ability to examine large samples at high magnifications without the need to section the material. A simple tissue preparation procedure is presented which allows this feature of SEM to be fully utilized and consistently produces high quality results. PMID- 22054562 TI - Pressure-heat treatment of meat: A comparison of beef and buffalo meat. AB - A pressure-heat treatment, which disrupts the myofibrillar structure of meat but leaves the connective tissues essentially intact, was used to compare the connective tissue component of toughness in the Semimembranosus and Longissimus dorsi muscles from nine Brahman cross and nine buffalo steers, 24 to 29 months of age. For assessment of samples, peak force, initial yield force and peak force minus initial yield force values were determined from Warner-Bratzler shear force deformation curves. In the control, non-pressure-heat treated samples, the only breed difference detected was in peak minus initial yield force value, which was significantly lower for the beef Semimembranosus muscles. However, for the pressure-heat treated samples of both muscles, peak force and peak minus initial yield force values were significantly lower for beef than for buffalo. The pressure-heat treatment could thus be used to detect differences in the contribution of connective tissue to toughness which would otherwise be obscured by the differences in the myofibrillar toughness. PMID- 22054563 TI - Electrical stimulation of rats: Part 2-The effect of electrical parameters on muscle tension and post-Mortem glycolysis. AB - Anaesthetized rats were used as a model to determine the effect of changes in electrical stimulation parameters on the pH fall of the M. longissimus dorsi and M. triceps surae and tension development by the M. triceps surae. Stimulation 5 min before decapitation resulted in a reduced post-stimulation fall in pH. Tension development resulting from stimulation of the sciatic nerve decreased rapidly 5 min after decapitation and ceased 30 min after decapitation, whereas a current pathway through the muscle was still effective. Post-stimulation pH fall was less in the leg not in the stimulation pathway, indicating a lack of crossover effect from one leg to the other; but the difference diminished as stimulation voltage increased. For direct stimulation, 20 V produced a maximal response in the stimulated leg; at least twice that voltage was required for a maximal pH fall in the leg not in the stimulation pathway. The total resistance of the rat with a needle electrode at the nape of the neck and crocodile clips attached to the unskinned legs was 3400 omega, whereas with skinned hindlegs the resistance was 860omega. With this high skin resistance at least 40 V was needed for effective stimulation whereas, for low voltage stimulation of much larger animals, only twice this voltage is used. High contact resistance and unknown current density factors make simple correlations of animal size and voltage effects impossible. The optimal stimulation frequency for rats was 20-30 pulses a second. If the cranial electrode was positive, about 15% more tension was developed than when the cranial electrode was negative. With alternating-polarity pulses, there was a high-low tension response, which was more pronounced at low voltages but evened out as the muscles became exhausted. Alternating and cranial positive pulses produced similar pH falls but cranial-negative pulses were inferior. PMID- 22054564 TI - Binding of comminuted meat: Effect of high pressure. AB - Patties prepared from comminuted meat were pressure-treated at up to 150 MPa at 0 3 degrees C and the cohesion between meat particles in the cooked patty investigated from tensile strength measurements. Pressure treatment increased tensile strength, the magnitude of the increase depending upon the intensity and duration of pressure treatment, the concentration of salt in the patty and pH value. The effect was most pronounced in patties of pH 5 to 6 and with 1% salt in the aqueous phase. Under these conditions cooking losses were reduced. When compared with the effect of addition of 0.5% tetrasodium pyrophosphate in a patty with 1% salt, pressure treatment retained its effect at lower pH values. PMID- 22054565 TI - Exploring the relationship between public environmental ethics and river flood policies in western Europe. AB - Two styles of river flood management can be distinguished: dike reinforcement and the more sustainable 'Room for River' option. This paper investigates public adherences to these two management styles and whether their adherence correlates with their Visions of Nature. The focus is especially on people's image of the appropriate human/nature relationship, i.e. Mastery over nature, Stewardship of nature, Partnership of nature or Participation in nature. Other variables that are part of the analysis are the respondents' sense of place, safety perception and background variables. The results of a written survey among riverside residents in France, Germany and the Netherlands (N = 1811) show high adherences to the Room for River style and a rejection of dike reinforcement. A regression analysis shows that adherence to the Room for River style correlates with adherence to the image of Stewardship, while adherence to dike reinforcement is predicted by Mastery over nature. Thus, according to the public a policy shift from dike reinforcement to a more sustainable style is seen as a fundamental one, connected to a change in environmental ethics. PMID- 22054566 TI - Assessment of arsenic immobilization in synthetically prepared cemented paste backfill specimens. AB - Mine tailings coming from the exploitation of sulphide and/or gold deposits can contain significant amounts of arsenic (As), highly soluble in conditions of weathering. Open mine voids backfilling techniques are now widely practiced by modern mining companies to manage the tailings. The most common one is called cemented paste backfill (CPB), and consists of tailings mixed with low amounts of hydraulic binders (3-5%) and a high proportion of water (typically 25%). The CPB is transported through a pipe network, to be placed in the mine openings. CPB provides storage benefits and underground support during mining operations. Moreover, this technique could also enhance contaminant stabilization, by fixing the contaminants in the binder matrix. CPB composites artificially spiked with As were synthesized in laboratory, using two types of hydraulic binders: a Portland cement, and a mix of fly ash and Portland cement. After curing duration of 66 days, the CPB samples were subjected to several leaching tests in various experimental conditions in order to better understand and then predict the As geochemical behaviour within CPBs. The assessment of the As release indicates that this element is better stabilized in Portland cement-based matrices rather than fly ash-based matrices. The As mobility differs in these two matrices, mainly because of the different As-bearing minerals formed during hydration processes. However, the total As depletion does not exceed 5% at the end of the most aggressive leaching test, indicating that As is well immobilized in the two types of CPB. PMID- 22054567 TI - Food safety assessment of planting patterns of four vegetable-type crops grown in soil contaminated by electronic waste activities. AB - A field experiment was conducted to assess the effect of crop and planting pattern on levels of cadmium (Cd), lead (Pb), and copper (Cu) in crops grown in soil contaminated by electronic waste. The crops were maize (Zea mays L. var. Shentian-1), tomato (Solanum lycopersicum L. var. Zhongshu-4), cabbage (Brassica oleracea L. var. Jingfeng-1), and pakchoi (Brassica chinensis (L.) Makino. var. Youdonger-Hangzhou). The planting patterns were crop monoculture, crop co-planted with a legume, and crop co-planted with another crop. Metal concentrations in the edible parts of the crops varied with types of metals and crops. Pb concentration was higher in leafy vegetables (cabbage and pakchoi) than in maize or tomato, Cd concentration was higher in tomato and pakchoi than in maize or cabbage, and Cu concentration was higher in maize and pakchoi than in tomato or cabbage. Metal concentrations in the edible part were also influenced by planting pattern. Relative to monoculture, co-planting and especially co-planting with Japanese clover tended to decrease Pb accumulation and increase Cd accumulation. According to the maximum permissible concentration (MPC) standard of the National Standard Agency in China, only maize (under all planting patterns) could be safely consumed. Because co-planting tended to increase Cd accumulation even in maize, however, the results suggest that maize monoculture is the optimal crop and planting pattern for this kind of contaminated soil. PMID- 22054568 TI - Kinetics of monomer biodegradation in soil. AB - In modern intensive agriculture, plastics are used in several applications (i.e. mulch films, drip irrigation tubes, string, clips, pots, etc.). Interest towards applying biodegradable plastics to replace the conventional plastics is promising. Ten monomers, which can be applied in the synthesis of potentially biodegradable polyesters, were tested according to ASTM 5988-96 (standard respirometric test to evaluate aerobic biodegradation in soil by measuring the carbon dioxide evolution): adipic acid, azelaic acid, 1,4-butanediol, 1,2 ethanediol, 1,6-hexanediol, lactic acid, glucose, sebacic acid, succinic acid and terephthalic acid. Eight replicates were carried out for each monomer for 27-45 days. The numerical code AQUASIM was applied to process the CO2 experimental data in order to estimate values for the parameters describing the different mechanisms occurring to the monomers in soil: i) the first order solubilization kinetic constant, K(sol) (d-1); ii) the first order biodegradation kinetic constant, K(b) (d-1); iii) the lag time in biodegradation, t(lag) (d); and iv) the carbon fraction biodegraded but not transformed into CO2, Y (-). The following range of values were obtained: [0.006 d-1, 6.9 d-1] for K(sol), [0.1 d 1, 1.2 d-1] for K(b), and [0.32-0.58] for Y; t(lag) was observed for azelaic acid, 1,2-ethanediol, and terephthalic acid, with estimated values between 3.0 e 4.9 d. PMID- 22054569 TI - Use of Escherichia coli BOX-PCR fingerprints to identify sources of fecal contamination of water bodies in the State of Sao Paulo, Brazil. AB - Repetitive element sequence-based polymerase chain reaction (rep-PCR) is one of the commonest methods used to identify sources of fecal contamination of water systems. In this work, BOX-A1R-based repetitive extragenic palindromic-PCR (BOX PCR) was used to discriminate Escherichia coli strains originating from different animals and water sources, and the suitability of the technique for bacterial source tracking (BST) was evaluated. A total of 214 strains from humans, 150 strains from animals, 55 strains from sewage and 77 strains from water bodies were analyzed by the BOX-PCR technique. When maximum similarity between the fingerprints was used, a correct classification rate of 84% was achieved for strains from human and animal sources. Furthermore, 95% of the strains found in sewage were classified as being from human sources by at least one of the four classification tools used. Classification of the strains found in water bodies in the State of Sao Paulo was based on the fingerprints obtained for human and animal sources. Most of the sampling sites appeared to be affected by mixed sources of fecal contamination. The use of BOX-PCR for BST could be especially valuable in developing countries, where simplicity and cost are important considerations. PMID- 22054570 TI - The relationship between milk production and farm-gate nitrogen surplus for the Waikato region, New Zealand. AB - As the scope and scale of New Zealand (NZ) dairy farming increases, farmers and the industry are being challenged by Government and the New Zealand public to address growing environmental concerns. Dairying has come under increasing scrutiny from local authorities tasked with sustainable resource management. Despite recent efforts of farmers and industry to improve resource use efficiency, there is increasing likelihood of further regulatory constraints on water use and nutrient management. This study uses available data on farm-gate nitrogen (N) surpluses and milk production from the Waikato, New Zealand's largest dairying region, together with a farm scale modeling exercise, to provide a perspective on the current situation compared to dairy farms in Europe. It also aims to provide relevant guidelines for N surpluses and efficiencies under NZ conditions. Waikato dairy farms compare favorably with farms in Europe in terms of N use efficiency expressed as L milk/kg farm-gate N surplus. Achievable and realistic good practice objectives for Waikato dairy farmers could be 15,000 L milk/ha (1200 kg milk fat plus protein/ha) with a farm-gate N surplus of 100 kg/ha giving an eco-efficiency (L milk/kg N surplus) of 150, and long-term average nitrate leaching losses of approximately 25-30 kg/ha/yr. This can be achieved by increasing the N conversion efficiency through lower replacement rates (16 versus 22%), lower stocked (< 3 cows/ha) high genetic merit cows (30 L milk/day at peak) milked for longer (277 versus 240 days), feeding effluent irrigated, home-grown, low-protein supplements to cows on high-protein, grass clover pastures to dilute N concentration in the diet, removing some of the urinary N from the paddocks during critical times by standing cows on a loafing pad for part of the day, and through lower N fertilizer rates (50-70 kg/ha/yr compared to the norm of 170-200 kg/ha/yr) and using a nitrification inhibitor and gibberellins to boost pasture growth and the former to reduce N leaching. PMID- 22054571 TI - Determining the native/non-native status of newly discovered terrestrial and freshwater species in Antarctica - current knowledge, methodology and management action. AB - Continental Antarctic terrestrial and freshwater environments currently have few established non-native species compared to the sub-Antarctic islands and other terrestrial ecosystems on Earth. This is due to a unique combination of factors including Antarctica's remoteness, harsh climate, physical geography and brief history of human activity. However, recent increases in national operator and tourism activities increase the risk of non-native propagules reaching Antarctica, while climate change may make successful establishment more likely. The frequency and probability of human-assisted transfer mechanisms appear to far outweigh those of natural propagule introductions by wind, water, birds and marine mammals. A dilemma for scientists and environmental managers, which is exacerbated by a poor baseline knowledge of Antarctic biodiversity, is how to determine the native/non-native status of a newly discovered species which could be (a) a previously undiscovered long-term native species, (b) a recent natural colonist or (c) a human-mediated introduction. A correct diagnosis is crucial as the Protocol on Environmental Protection to the Antarctic Treaty dictates dramatically different management responses depending on native/non-native status: native species and recent natural colonists should be protected and conserved, while non-native introductions should be eradicated or controlled. We review current knowledge on how available evidence should be used to differentiate between native and non-native species, and discuss and recommend issues that should be considered by scientists and managers upon discovery of a species apparently new to the Antarctic region. PMID- 22054572 TI - Solids and nutrient removal from flushed swine manure using polyacrylamides. AB - Most of the organic nutrient elements (nitrogen and phosphorus) and carbon compounds in liquid swine are contained in fine suspended particles. Flocculation treatment with polyacrylamide (PAM) followed by screening is one the best methods to separate the liquid fraction from the solid fraction in swine manure, and thus to eliminate nutrient elements associated with solids. In this study, the efficiency of a synthetic polyacrylamide to treat swine manure was evaluated. After polymer treatment samples were sieved and the filtrated liquid was analyzed. TSS, VSS and COD concentrations in the liquid fraction were 2.17, 1.93 and 16.42 g/L respectively, accounting for 94, 94 and 77% removal percentages for TSS, VSS and COD using 30 mg/L of PAM. PMID- 22054573 TI - Integrating local ecological knowledge and management practices of an isolated semi-arid papyrus swamp (Loboi, Kenya) into a wider conservation framework. AB - The current study documented local utilization of Cyperus papyrus L. (papyrus), harvesting patterns, threats, and local management practices among the Endorois community living around Loboi swamp (Kenya). Papyrus is a highly productive freshwater macrophyte that is widely utilized throughout tropical Africa. However, increased human population and poverty, has led to over exploitation and conversion of papyrus wetlands to agricultural fields. Nonetheless, users of papyrus hold important local ecological knowledge (LEK) and practices. We show that Endorois practices on papyrus uses are compatible with the management priorities of the swamp and a wider conservation framework using data obtained from three focus group discussions (FGD), interviews of 34 households and 15 key informants. The study revealed that papyrus support local livelihood notably as a source of income (papyrus mats are sold), cattle fodder, roofing materials (shelter), and cooking fuel. The study further revealed important LEK relating to harvesting patterns, recovery after harvesting and traditional management practices. Correlation and principal component analyses showed that experienced old harvesters (EXPERT) avoided harvesting repeatedly at the same location (REVISIT), thereby allowing recovery of papyrus when compared to younger harvesters (r = 0.63, p < 0.01). However, over 70% of harvesters predicted a decrease in papyrus coverage in the future due to the current diversion of water from the swamp, and frequent droughts, despite the instituted traditional management strategies (e.g. rotational harvesting) to curb overharvesting. The study concluded that the documentation of site-scale papyrus users' profile, LEK, and traditional practices are vital for the conservation and management of Loboi swamp. PMID- 22054574 TI - Odour-impact assessment around a landfill site from weather-type classification, complaint inventory and numerical simulation. AB - Gases released from landfill sites into the atmosphere have the potential to cause olfactory nuisances within the surrounding communities. Landfill sites are often located over complex topography for convenience mainly related to waste disposal and environmental masking. Dispersion of odours is strongly conditioned by local atmospheric dynamics. Assessment of odour impacts needs to take into account the variability of local atmospheric dynamics. In this study, we discuss a method to assess odour impacts around a landfill site located over complex terrain in order to provide information to be used subsequently to identify management strategies to reduce olfactory nuisances in the residential neighbourhoods. A weather-type classification is defined in order to identify meteorological conditions under which olfactory nuisances are to be expected. A non-steady state Gaussian model and a full-physics meteorological model are used to predict olfactory nuisances, for both the winter and summer scenarios that lead to the majority of complaints in neighbourhoods surrounding the landfill site. Simulating representative scenarios rather than full years make a high resolution simulation of local atmospheric dynamics in space and time possible. Results underline the key role of local atmospheric dynamics in driving the dispersion of odours. The odour concentration simulated by the full-physics meteorological model is combined with the density of the population in order to calculate an average population exposure for the two scenarios. Results of this study are expected to provide helpful information to develop technical solutions for an effective management of landfill operations, which would reduce odour impacts within the surrounding communities. PMID- 22054575 TI - Performance measurement for incineration plants using multi-activity network data envelopment analysis: The case of Taiwan. AB - This study proposes the use of multi-activity network data envelopment analysis to appraise how incineration plants in Taiwan perform. Sample data from 2006 is used to examine the trade-offs between efficiency enhancement and pollution abatement. The respective efficiencies of the waste treatment and electricity generation are also assessed in a unified framework. The empirical results indicate that it is more important to improve the efficiency of waste treatment activity than of electricity generation activity in order to enhance the overall performance of Taiwan's incinerators. Since ownership, location and length of operations do not in general affect their performance, any improvement has to come from the careful monitoring of each process of the waste treatment operations. Furthermore, given that the policy in Taiwan has moved away from incineration to recycling, the problem of an over-supply of incinerators may become apparent in the near future. Our results indicate that the availability of capacity size may be an important factor when policy-makers consider whether to close down some existing incinerators. PMID- 22054576 TI - Benefit-cost analysis of spruce budworm (Choristoneura fumiferana Clem.) control: incorporating market and non-market values. AB - This study employs a benefit-cost analysis framework to estimate market and non market benefits and costs of controlling future spruce budworm (Choristoneura fumiferana) outbreaks on Crown forest lands in New Brunswick, Canada. We used: (i) an advanced timber supply model to project potential timber volume saved, timber value benefits, and costs of pest control efforts; and (ii) a recent contingent valuation method analysis that evaluated non-market benefits (i.e., changes in recreation opportunities and existence values) of controlling future spruce budworm outbreaks in the Province. A total of six alternative scenarios were evaluated, including two uncontrolled future budworm outbreak severities (moderate vs. severe) and, for each severity, three control program levels (protecting 10%, 20%, or 40% of the susceptible Crown land forest area). The economic criteria used to evaluate each scenario included benefit-cost ratios and net present values. Under severe outbreak conditions, results indicated that the highest benefit-cost ratio (4.04) occurred when protecting 10% (284,000 ha) of the susceptible area, and the highest net present value ($111 M) occurred when protecting 20% (568,000 ha) of the susceptible area. Under moderate outbreak conditions, the highest benefit-cost ratio (3.24) and net present value ($58.7 M) occurred when protecting 10% (284,000 ha) of the susceptible area. Inclusion of non-market values generally increased the benefit-cost ratios and net present values of the control programs, and in some cases, led to higher levels of control being supported. Results of this study highlight the importance of including non-market values into the decision making process of forest pest management. PMID- 22054577 TI - The potential of epiphytic hydrocarbon-utilizing bacteria on legume leaves for attenuation of atmospheric hydrocarbon pollutants. AB - The leaves of two legumes, peas and beans, harbored on their surfaces up to 9*107 cells g-1 of oil-utilizing bacteria. Less numbers, up to 5*105 cells g-1 inhabited leaves of two nonlegume crops, namely tomato and sunflower. Older leaves accommodated more of such bacteria than younger ones. Plants raised in oily environments were colonized by much more oil-utilizing bacteria than those raised in pristine (oil-free) environments. Similar numbers were counted on the same media in which nitrogen salt was deleted, indicating that most phyllospheric bacteria were probably diazotrophic. Most dominant were Microbacterium spp. followed by Rhodococcus spp., Citrobacter freundii, in addition to several other minor species. The pure bacterial isolates could utilize leaf tissue hydrocarbons, and consume considerable proportions of crude oil, phenanthrene (an aromatic hydrocarbon) and n-octadecane (an alkane) in batch cultures. Bacterial consortia on fresh (but not on previously autoclaved) leaves of peas and beans could also consume substantial proportions of the surrounding volatile oil hydrocarbons in closed microcosms. It was concluded that phytoremediation through phyllosphere technology could be useful in remediating atmospheric hydrocarbon pollutants. PMID- 22054578 TI - Air quality impact assessment of multiple open pit coal mines in northern Colombia. AB - The coal mining region in northern Colombia is one of the largest open pit mining regions of the world. In 2009, there were 8 mining companies in operation with an approximate coal production of ~70 Mtons/year. Since 2007, the Colombian air quality monitoring network has reported readings that exceed the daily and annual air quality standards for total suspended particulate (TSP) matter and particles with an equivalent aerodynamic diameter smaller than 10 MUm (PM10) in nearby villages. This paper describes work carried out in order to establish an appropriate clean air program for this region, based on the Colombian national environmental authority requirement for modeling of TSP and PM(10) dispersion. A TSP and PM10 emission inventory was initially developed, and topographic and meteorological information for the region was collected and analyzed. Using this information, the dispersion of TSP was modeled in ISC3 and AERMOD using meteorological data collected by 3 local stations during 2008 and 2009. The results obtained were compared to actual values measured by the air quality monitoring network. High correlation coefficients (>0.73) were obtained, indicating that the models accurately described the main factors affecting particle dispersion in the region. The model was then used to forecast concentrations of particulate matter for 2010. Based on results from the model, areas within the modeling region were identified as highly, fairly, moderately and marginally polluted according to local regulations. Additionally, the contribution particulate matter to the pollution at each village was estimated. Using these predicted values, the Colombian environmental authority imposed new decontamination measures on the mining companies operating in the region. These measures included the relocation of three villages financed by the mine companies based on forecasted pollution levels. PMID- 22054579 TI - Alternative approaches to dealing with respondent uncertainty in contingent valuation: a comparative analysis. AB - Several strategies have been proposed to deal with response uncertainty in contingent valuation. One approach, often applied to address issues of hypothetical bias, recodes and/or reweights responses according to stated levels of certainty but so far few analyses compare alternative recoding and reweighting strategies. We explore the choice among alternative strategies that exploit a numerical certainty scale obtained from a follow-up to the payment question in a valuation survey about a whale conservation program. Two novel variations of previously followed approaches perform best on our dataset in terms of the efficiency of estimates. The first one uses an exponential transformation of the numerical certainty scale as a weight in the willingness to pay regression. The other one is based on constructing a continuous willingness to pay variable with the highly certain "yes" and "no" original responses to the payment question as extreme values and with mid-point values that correspond to the original "don't know" responses. We find, though, that the effect of using different treatment strategies on mean willingness to pay is rarely statistically significant and we fail to detect a consistent effect on the efficiency of the estimation regardless of the strategy applied. PMID- 22054580 TI - Does control of soil erosion inhibit aquatic eutrophication? AB - Much of the phosphorus (P) from erosive soils is transported to water bodies together with eroded soil. Studies clarifying the impact of soil erosion on eutrophication have sought largely to quantify the reserves of P in soil particles that can be desorbed in different types of receiving waters. Aquatic microbiology has revealed that the cycling of P is coupled to the availability of common electron acceptors, Fe oxides and SO4, through anaerobic mineralization in sediments. Eroded soil is also rich in Fe oxides, and their effect on the coupled cycling of C, Fe, S, and P has been neglected in eutrophication research. Soil erosion, and its control, should therefore be studied by considering not only the processes occurring in the water phase but also those taking place after the soil particles have settled to the bottom. We propose that in SO4-rich systems, Fe oxides transported by eroded soil may promote Fe cycling, inhibit microbial SO4 reduction and maintain the ability of sediment to retain P. We discuss the mechanisms through which eroded soil may affect benthic mineralization processes and the manner in which soil erosion may contribute to or counteract eutrophication. PMID- 22054581 TI - Design and operational parameters of a rooftop rainwater harvesting system: definition, sensitivity and verification. AB - The appropriate design and evaluation of a rainwater harvesting (RWH) system is necessary to improve system performance and the stability of the water supply. The main design parameters (DPs) of an RWH system are rainfall, catchment area, collection efficiency, tank volume and water demand. Its operational parameters (OPs) include rainwater use efficiency (RUE), water saving efficiency (WSE) and cycle number (CN). The sensitivity analysis of a rooftop RWH system's DPs to its OPs reveals that the ratio of tank volume to catchment area (V/A) for an RWH system in Seoul, South Korea is recommended between 0.03 and 0.08 in terms of rate of change in RUE. The appropriate design value of V/A is varied with D/A. The extra tank volume up to V/A of 0.15~0.2 is also available, if necessary to secure more water. Accordingly, we should figure out suitable value or range of DPs based on the sensitivity analysis to optimize design of an RWH system or improve operation efficiency. The operational data employed in this study, which was carried out to validate the design and evaluation method of an RWH system, were obtained from the system in use at a dormitory complex at Seoul National University (SNU) in Korea. The results of these operational data are in good agreement with those used in the initial simulation. The proposed method and the results of this research will be useful in evaluating and comparing the performance of RWH systems. It is found that RUE can be increased by expanding the variety of rainwater uses, particularly in the high rainfall season. PMID- 22054582 TI - A review on chemical coagulation/flocculation technologies for removal of colour from textile wastewaters. AB - Textile industry is one of the most chemically intensive industries on the earth and the major polluter of potable water. It generates huge quantities of complex chemical substances as a part of unused materials including dyes in the form of wastewater during various stages of textile processing. The direct discharge of this wastewater into environment affects its ecological status by causing various undesirable changes. As environmental protection becomes a global concern, industries are finding novel solutions for developing technologies that can diminish the environmental damage. However, colour removal from textile wastewater by means of cheaper and environmental friendly technologies is still a major challenge. In this manuscript, several options of decolourisation of textile wastewater by chemical means have been reviewed. Based on the present review, some novel pre-hydrolysed coagulants such as Polyaluminium chloride (PACl), Polyaluminium ferric chloride (PAFCl), Polyferrous sulphate (PFS) and Polyferric chloride (PFCl) have been found to be more effective and suggested for decolourisation of the textile wastewater. Moreover, use of natural coagulants for textile wastewater treatment has also been emphasised and encouraged as the viable alternative because of their eco-friendly nature. PMID- 22054583 TI - Does the Coase theorem hold in real markets? An application to the negotiations between waterworks and farmers in Denmark. AB - The Coase theorem depends on a number of assumptions, among others, perfect information about each other's payoff function, maximising behaviour and zero transaction costs. An important question is whether the Coase theorem holds for real market transactions when these assumptions are violated. This is the question examined in this paper. We consider the results of Danish waterworks' attempts to establish voluntary cultivation agreements with Danish farmers. A survey of these negotiations shows that the Coase theorem is not robust in the presence of imperfect information, non-maximising behaviour and transaction costs. Thus, negotiations between Danish waterworks and farmers may not be a suitable mechanism to achieve efficiency in the protection of groundwater quality due to violations of the assumptions of the Coase theorem. The use of standard schemes or government intervention (e.g. expropriation) may, under some conditions, be a more effective and cost efficient approach for the protection of vulnerable groundwater resources in Denmark. PMID- 22054584 TI - The status and importance of crude protein and macro minerals in native pastures growing on Vertisols of the central highlands of Ethiopia. AB - The effects of pasture management, season and soil nutrient status on crude protein (CP) and macro mineral concentration of native pasture was studied in the Vertisol areas of the central Ethiopian highland. Soil and herbage samples from 18 continuously grazed (CG) and 12 seasonally grazed (SG) pasture sites were analyzed for N, P, Ca, Mg, K and Na. Soil and dry season CG pasture samples were collected in January and February 2001 (dry season: November-February), while wet season CG and SG pasture samples were collected during September 2001 (wet season: April-October). The Potassium concentration (2.55%) of mixed herbage samples from SG pasture exceeded the K values (1.80%) from CG pasture (P < 0.01). Significant (P < 0.01) differences of CP and macro minerals concentrations were noted among forage species. The mean CP and K concentrations of herbage from CG pasture were higher (P < 0.01) during the wet than during the dry season (5.97 and 1.80% vs. 3.18 and 0.79%), while the opposite was true for Ca (0.49% vs. 0.61%) (P < 0.05). Regarding soil macro minerals and the corresponding herbage macro mineral concentrations, significant (P < 0.05) but inconsistent correlations were found for Ca, P, Mg and Na. The results suggest that pasture management, season and to some extend soil nutrient status, can affect herbage CP and macro mineral composition. The levels of CP in CG pasture and that of P and Na in both CG and SG pastures may fall below the requirements of grazing livestock. Resting at critical stages of the growth cycle of the forage species encouraged the recovery of desirable species. For this reason resting of pasture can contribute significantly to the quality of the native pastures of the Vertisols of the central Ethiopian highlands and should be encouraged. PMID- 22054585 TI - Sediment amendment with Phoslock(r) in Clatto Reservoir (Dundee, UK): Investigating changes in sediment elemental composition and phosphorus fractionation. AB - Lanthanum-modified bentonite clay (Phoslock((r)) is a lake remediation tool designed to strip dissolved phosphorus (P) from the water column and increase the sediment P-sorption capacity. This study investigated short term alterations in sediment elemental composition and sediment P-fractions based on sediment cores taken 2 days before and 28 days following the application of 24 t of Phoslock(r) to a 9 ha, man-made reservoir. Following the application, sediment lanthanum (La) content increased significantly (p < 0.05; n = 4) in the top 8 cm of the sediment, thereby theoretically increasing sediment P-binding capacity on the whole reservoir scale by 250 kg. Mass balance calculations were used to estimate the theoretical binding of release-sensitive P (P(mobile); sum of 'labile P', 'reductant-soluble P' and 'organic P' fraction) by La across the top 4 cm and 10 cm depth of sediment. The amended mass of La in the sediment had the potential to bind 42% of P(mobile) present in the top 4 cm or 17% of P(mobile) present in the top 10 cm. However, with the exception of a significant increase (p<0.05; n=4) in the 'residual P' fraction in the top 2 cm, sediment P-fractions, including P(mobile,) did not differ significantly following the Phoslock(r) application. Experimental P-adsorption studies indicated P-saturation values for Phoslock(r) of 21,670 mg P kg-1 Phoslock(r). Sequential extraction of P from saturated Phoslock(r) under laboratory conditions indicated that around 21% of P bound by Phoslock(r) was release-sensitive, while around 79% of bound P was unlikely to be released under reducing or common pH (5-9) conditions in shallow lakes. Applying Phoslock(r) is, therefore, likely to increase the P-sorption capacity of sediments under reducing conditions. PMID- 22054586 TI - From the LCA of food products to the environmental assessment of protected crops districts: a case-study in the south of Italy. AB - In the present study, Life Cycle Assessment (LCA) methodology was applied to evaluate the energy consumption and environmental burdens associated with the production of protected crops in an agricultural district in the Mediterranean region. In this study, LCA was used as a 'support tool', to address local policies for sustainable production and consumption patterns, and to create a 'knowledge base' for environmental assessment of an extended agricultural production area. The proposed approach combines organisation-specific tools, such as Environmental Management Systems and Environmental Product Declarations, with the environmental management of the district. Questionnaires were distributed to producers to determine the life cycle of different protected crops (tomatoes, cherry tomatoes, peppers, melons and zucchinis), and obtain information on greenhouse usage (e.g. tunnel vs. pavilion). Ecoprofiles of products in the district were also estimated, to identify supply chain elements with the highest impact in terms of global energy requirements, greenhouse gas emissions, eutrophication, water consumption and waste production. These results of this study enable selection of the 'best practices' and ecodesign solutions, to reduce the environmental impact of these products. Finally, sensitivity analysis of key LCA issues was performed, to assess the variability associated with different parameters: vegetable production; water usage; fertiliser and pesticide usage; shared greenhouse use; substitution of plastics coverings; and waste recycling. PMID- 22054587 TI - Process analysis and economics of drinking water production from coastal aquifers containing chromophoric dissolved organic matter and bromide using nanofiltration and ozonation. AB - In regions characterized by water scarcity, such as coastal Southern California, groundwater containing chromophoric dissolved organic matter is a viable source of water supply. In the coastal aquifer of Orange County in California, seawater intrusion driven by coastal groundwater pumping increased the concentration of bromide in extracted groundwater from 0.4 mg l-1 in 2000 to over 0.8 mg l-1 in 2004. Bromide, a precursor to bromate formation is regulated by USEPA and the California Department of Health as a potential carcinogen and therefore must be reduced to a level below 10 MUg l-1. This paper compares two processes for treatment of highly coloured groundwater: nanofiltration and ozone injection coupled with biologically activated carbon. The requirement for bromate removal decreased the water production in the ozonation process to compensate for increased maintenance requirements, and required the adoption of catalytic carbon with associated increase in capital and operating costs per unit volume. However, due to the absence of oxidant addition in nanofiltration processes, this process is not affected by bromide. We performed a process analysis and a comparative economic analysis of capital and operating costs for both technologies. Our results show that for the case studied in coastal Southern California, nanofiltration has higher throughput and lower specific capital and operating cost, when compared to ozone injection with biologically activate carbon. Ozone injection with biologically activated carbon, compared to nanofiltration, has 14% higher capital cost and 12% higher operating costs per unit water produced while operating at the initial throughput. Due to reduced ozone concentration required to accommodate for bromate reduction, the ozonation process throughput is reduced and the actual cost increase (per unit water produced) is 68% higher for capital cost and 30% higher for operations. PMID- 22054588 TI - Life cycle of meats: an opportunity to abate the greenhouse gas emission from meat industry in Japan. AB - The food industry is one of the world's largest industrial sectors, hence a large contributor of greenhouse gases (GHG) which cause global warming. This study evaluates the life cycle of various types of meat to determine if the GHG emission from the meat industry in Japan could be reduced if the population makes different dietary choices. It was confirmed that the GHG emission of beef was greater than that of pork or chicken. The GHG emission from meat in general also depends on the per capita caloric intake (if meat supplies the recommended animal protein or contributes to it at the present rate). In a healthy and balanced diet (9.2 MJ i.e., 2200 kcal in total, where either mixed meat or chicken or pork or beef contributes 2.2%), the GHG emission is estimated to be 0.28 or 0.17 or 0.15 or 0.77 kg CO2 eq/person/day, respectively. A change in consumption patterns (from beef to chicken or pork) and the adoption of a healthy and balanced diet would help to abate about 2.5-54.0 million tons (CO2 eq) produced by the meat industry each year in Japan. PMID- 22054589 TI - Approaches to the implementation of the Water Framework Directive: targeting mitigation measures at critical source areas of diffuse phosphorus in Irish catchments. AB - The Water Framework Directive (WFD) has initiated a shift towards a targeted approach to implementation through its focus on river basin districts as management units and the natural ecological characteristics of waterbodies. Due to its role in eutrophication, phosphorus (P) has received considerable attention, resulting in a significant body of research, which now forms the evidence base for the programme of measures (POMs) adopted in WFD River Basin Management Plans (RBMP). Targeting POMs at critical sources areas (CSAs) of P could significantly improve environmental efficiency and cost effectiveness of proposed mitigation strategies. This paper summarises the progress made towards targeting mitigation measures at CSAs in Irish catchments. A review of current research highlights that knowledge related to P export at field scale is relatively comprehensive however; the availability of site-specific data and tools limits widespread identification of CSA at this scale. Increasing complexity of hydrological processes at larger scales limits accurate identification of CSA at catchment scale. Implementation of a tiered approach, using catchment scale tools in conjunction with field-by-field surveys could decrease uncertainty and provide a more practical and cost effective method of delineating CSA in a range of catchments. Despite scientific and practical uncertainties, development of a tiered CSA-based approach to assist in the development of supplementary measures would provide a means of developing catchment-specific and cost-effective programmes of measures for diffuse P. The paper presents a conceptual framework for such an approach, which would have particular relevance for the development of supplementary measures in High Status Waterbodies (HSW). The cost and resources necessary for implementation are justified based on HSWs' value as undisturbed reference condition ecosystems. PMID- 22054590 TI - Feasibility of CO2/SO2 uptake enhancement of calcined limestone modified with rice husk ash during pressurized carbonation. AB - The calcination/carbonation cycle using calcium-based sorbents appears to be a viable method for carbon dioxide (CO2) capture from combustion gases. Recent attempts to improve the CO2/SO2 uptake of a calcium-based sorbent modified by using rice husk ash (RHA) in the hydration process have succeeded in enhancing its effectiveness. The optimal mole ratio of RHA to calcined limestone (M(Si/Ca)) was adjusted to 0.2. The cyclic CO2 capture characteristics and the SO2 uptake activity of the modified sorbent were evaluated in a calcination/pressurized carbonation reactor system. Scanning electron microscope (SEM) images and X-ray diffraction (XRD) spectrum of the sorbent were also taken to supplement the study. The results showed that the carbonation conversion was greatly increased for the sorbent with M(Si/Ca) ratio of 0.2. For this sorbent formulation the optimal operating conditions were 700-750 degrees C and 0.5-0.7 MPa. CO2 absorption was not proportional to CO2 concentration in the carbonation atmosphere, but was directly related to reaction time. The CO2 uptake decreased in the presence of SO2. SO2 uptake increased, and the total calcium utilization was maintained over multiple cycles. Analysis has shown that the silicate component is evenly or well distributed, and this serves as a framework to prevent sintering, thus preserving the available microstructure for reaction. The sorbent also displayed high activity to SO2 absorption and could be used to capture CO2 and SO2 simultaneously. PMID- 22054591 TI - Effects of impurities on the removal of heavy metals by natural limestones in aqueous systems. AB - Effects of impurities on the removal of heavy metals by natural limestones in aqueous solutions were studied by evaluating various factors including limestone concentration, pH, contact time and temperature. Solutions of Pb(II), Cd(II), Cu(II) and Zn(II), prepared from chloride reagents at a concentration of 10 mg/L, were studied in a batch method. Four natural limestone samples, collected from the Campanian-Maastrichtian limestone beds in Tunisia, were used as adsorbents. Sorption experiments indicated that high removal efficiencies could be achieved. Limestone samples containing impurities, such as silica, iron/aluminum oxides and different kinds of clay minerals, demonstrated enhanced sorption capacity, nearing 100% removal in some cases. Kinetic experiments showed that the sorption of metal ions occurred rapidly at a low coverage stage, and that solutions were nearly at equilibrium after 60 min. Data trends generally fit pseudo-second order kinetic, and intra-particle diffusion, models. The following conditions were found to promote optimum, or near-optimum, sorption of heavy metals: 1) contact time of more than 60 min, 2) pH = 5, 3) >3 g/L limestone concentration and 4) T = 35 degrees C. The results of this study suggest that the limestones from northern Tunisia, that contain higher amounts of silica and iron/aluminum oxides, are promising adsorbents for the effective removal of toxic heavy metals from wastewaters. PMID- 22054592 TI - Ecological network analysis of China's societal metabolism. AB - Uncontrolled socioeconomic development has strong negative effects on the ecological environment, including pollution and the depletion and waste of natural resources. These serious consequences result from the high flows of materials and energy through a socioeconomic system produced by exchanges between the system and its surroundings, causing the disturbance of metabolic processes. In this paper, we developed an ecological network model for a societal system, and used China in 2006 as a case study to illustrate application of the model. We analyzed China's basic metabolic processes and used ecological network analysis to study the network relationships within the system. Basic components comprised the internal environment, five sectors (agriculture, exploitation, manufacturing, domestic, and recycling), and the external environment. We defined 21 pairs of ecological relationships in China's societal metabolic system (excluding self mutualism within a component). Using utility and throughflow analysis, we found that exploitation, mutualism, and competition relationships accounted for 76.2, 14.3, and 9.5% of the total relationships, respectively. In our trophic level analysis, the components were divided into producers, consumers, and decomposers according to their positions in the system. Our analyses revealed ways to optimize the system's structure and adjust its functions, thereby promoting healthier socioeconomic development, and suggested ways to apply ecological network analysis in future socioeconomic research. PMID- 22054593 TI - Perioperative variables associated with surgical site infection in breast cancer surgery. AB - Despite the fact that breast operations are usually categorized as clean procedures, higher surgical site infection (SSI) rates are reported. This study aimed to determine the perioperative variables related to SSI in breast cancer patients. Medical records of breast cancer patients undergoing surgery between January 2005 and August 2007 at a university based hospital were reviewed. Preoperative, intraoperative, and postoperative clinical data from 199 patients were extracted and analysed. Overall, the SSI rate was 19.1% (38 cases). SSI was associated with a high body mass index (P=0.001), history of diabetes mellitus (P<0.0001), smoking (P<0.0001), or active skin disorders (P<0.0001). Other SSI related variables included a tumour at an advanced clinical stage (P=0.003) and neoadjuvant therapy (P=0.003). Breast-conserving operations were less frequently associated with SSI than were radical procedures (mastectomy alone and mastectomy followed by immediate reconstruction) (P=0.0001). PMID- 22054594 TI - Blood culture contamination: having your cake and eating it. PMID- 22054595 TI - Are qacG, qacH and qacJ genes transferring from food isolates to carriage isolates of staphylococci? PMID- 22054596 TI - A bundle of care to reduce colorectal surgical infections: an Australian experience. Is it the real revolution? PMID- 22054597 TI - Chronic sciatic nerve injury impairs the local cutaneous neurovascular interaction in rats. AB - Most studies of chronic nerve compression focus on large nerve function in painful conditions, and only few studies have assessed potential changes in the function of small nerve fibers during chronic nerve compression and recovery from compression. Cutaneous pressure-induced vasodilation is a neurovascular phenomenon that relies on small neuropeptidergic fibers controlling the cutaneous microvasculature. We aimed to characterize potential changes in function of these small fibers and/or in cutaneous microvascular function following short-term (1 month) and long-term (6-month) nerve compression and after release of compression (ie, potential recovery of function). A compressive tube was left on one sciatic nerve for 1 or 6 months and then removed for 1-month recovery in Wistar rats. Cutaneous vasodilator responses were measured by laser Doppler flowmetry in hind limb skin innervated by the injured nerve to assess neurovascular function. Nociceptive thermal and low mechanical thresholds were evaluated to assess small and large nerve fiber functions, respectively. Pressure-induced vasodilation was impaired following nerve compression and restored following nerve release; both impairment and restoration were strongly related to duration of compression. Small and large nerve fiber functions were less closely related to duration of compression. Our data therefore suggest that cutaneous pressure-induced vasodilation provides a non-invasive and mechanistic test of neurovascular function that gives direct information regarding extent and severity of damage during chronic nerve compression and recovery, and may ultimately provide a clinically useful tool in the evaluation of nerve injury such as carpal tunnel syndrome. PMID- 22054598 TI - Re-evaluation of the phenotypic changes in L4 dorsal root ganglion neurons after L5 spinal nerve ligation. AB - The L5 spinal nerve ligation (SNL) is a widely used animal neuropathic pain model. There are conflicting reports regarding the extent of injury to the L4 dorsal root ganglion (DRG) neurons in this model. If a significant number of these neurons were injured, the previously reported phenotypic and electrophysiological changes at this level are in need of re-evaluation by separating the injured neurons and the frankly spared ones. So, we immunostained activating transcription factor 3 (ATF3) and examined the change in expression of transcripts for neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF) and several voltage-gated sodium channel alpha-subunits (Nav1.1, Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9) in the L4 DRG by comparing signal intensities of individual neurons using in situ hybridization histochemistry. ATF3 immunoreactivity was similarly observed in 4-6% of neuronal nuclei of the SNL and sham-operated ipsilateral L4 DRGs. Comparison between ATF3+ and ATF3- neurons in the SNL L4 DRG revealed that (1) whereas NPY induction occurred in ATF3+ cells, BDNF increased mainly in ATF3- neurons; (2) although ATF3+ neurons had higher Nav1.3 signals than ATF3- neurons, these signals were much lower than those of the L5 DRG neurons; and (3) ATF3+/N52- neurons selectively lost Nav1.8 and Nav1.9 mRNAs. Comparison of the total neuronal populations among naive, SNL, and sham operated rats revealed no significant differences for all examined Nav mRNAs. Because neuropathic pain behaviors were developed by rats with SNL but not the sham-operation, the small number of injured L4 neurons likely do not contribute to the pathomechanisms of neuropathic pain. PMID- 22054599 TI - Peripheral and spinal GABAergic regulation of incisional pain in rats. AB - Impairment of spinal GABAergic inhibition is demonstrated to contribute to pathologic chronic pain states. We investigated spinal and peripheral GABAergic regulation of incisional pain in rats. We found that intrathecal but not peripheral administration of muscimol (GABA-A receptor agonist) and baclofen (GABA-B receptor agonist) reduced mechanical and thermal hyperalgesia after plantar incision in rats. Nonevoked pain behavior after incision was unaffected by these agonists. Similarly, nociception in unincised rats was not reduced by the same dose of agonists. Thus, GABA-A and GABA-B receptors are involved in mediating incision-induced hyperalgesia (but not nonevoked pain). Intrathecal and systemic application of L-838,417, a subtype-selective benzodiazepine site agonist (alpha2, alpha3, alpha5), reduced mechanical and heat hyperalgesia after incision, indicating a role of these subunits in mediating incision-induced hyperalgesia. Interestingly, the effects of all agonists were more intense and prolonged on the day after surgery than on the day of incision. Similarly, spinally administered GABA-A and GABA-B antagonists increased pain behavior, again with a greater effect 1 day after incision. One possible explanation for this finding might be that an incision modulates GABA-mediated inhibition 1 day after incision. However, expression of GABA-A receptor subunits alpha2 and alpha3 and GABA-B receptor subunits within the dorsal horn of the spinal cord were unchanged after incision, indicating that receptor expression cannot explain a possible modulation of GABAergic inhibition after incision. Thus, other mechanisms need to be considered. In conclusion, GABA-A and GABA-B receptors are promising targets for postoperative, incisional pain in humans. PMID- 22054601 TI - A comparison of the effects of electrical, captive bolt or percussion stunning on the incidence of blood splash in lambs. AB - Three-hundred-and-three lambs were divided into three equal groups. Half the lambs in each group were not weaned before slaughter and the weaned half were slaughtered a week later. Lambs in one group were head stunned electrically before slaughter; in the second group lambs were stunned with a captive bolt pistol and in the third group they were percussion stunned before slaughter. Carcasses, gall-bladders, hearts and duodenums were inspected for blood splash after slaughter. A few small haemorrhages were detected in 57% of the electrically stunned lambs, in 30% of the captive bolt stunned lambs and in only 16% of the percussion stunned animals. Although no splash of commercial significance was found in any carcass, 25% of the electrically stunned lambs had detectably splashed carcasses, whilst only 1% of percussion-stunned lambs had splashed carcasses with captive bolt stunned lambs being intermediate in carcass splash incidence. These results show that stunning method affects the incidence of blood splash. PMID- 22054600 TI - Does fear of movement mediate the relationship between pain intensity and disability in patients following whiplash injury? A prospective longitudinal study. AB - The aim of this study was to test the capacity of the Fear Avoidance Model to explain the relationship between pain and disability in patients with whiplash associated disorders. Using the method of Baron and Kenny, we assessed the mediating effect of fear of movement on the cross-sectional and longitudinal relationships between pain and disability. Two hundred and five subjects with neck pain due to a motor vehicle accident provided pain intensity (0 to 10 numerical rating scale), fear of movement (Tampa Scale of Kinesiophobia and Pictorial Fear of Activity Scale) and disability (Neck Disability Index) scores within 4 weeks of their accident, after 3 months, and after 6 months. The analyses were consistent with the Fear Avoidance Model mediating approximately 20% to 40% of the relationship between pain and disability. Contrary to our initial hypothesis, the proportion of the total effect of pain on disability that was mediated by fear of movement did not substantially change as increasing time elapsed after the accident. The proportion mediated was slightly higher when fear of movement was measured by Tampa Scale of Kinesiophobia as compared with Pictorial Fear of Activity Scale. The findings of this study suggest that the Fear Avoidance Model plays a role in explaining a moderate proportion of the relationship between pain and disability after whiplash injury. PMID- 22054602 TI - Carcass characteristics and meat quality of halothane negative and halothane positive pietrain pigs. AB - One hundred and seventy-six Pietrain pigs were tested for halothane sensitivity by means of a 5-min halothane anaesthesia in two experiments. One hundred and twenty were halothane negative (HN) and 56 were halothane positive (HP). In one experiment pigs were slaughtered under commercial (stress) conditions; in the other experiment pigs were killed under minimal stress conditions. The carcasses of HP pigs were meatier and shorter and contained 2.2% more muscle than the carcasses of HN pigs. Halothane positive pigs gave a meat of poorer quality, as assessed in the fresh state. When the pigs were slaughtered under commercial conditions, hams from HP pigs were not inferior in curing ability and had a higher total processing yield of Paris ham due to their higher trimming yield. When the pigs were killed under minimal stress conditions, there was no difference in the total processing yield betwen HN and HP pigs, because the technological yield was markedly reduced in HP pigs. However, in both cases, HP pigs produced more cooked ham per pig. It is suggested that different physiological mechanisms may account for either PSE (pale soft exudative) or DFD (dark firm dry) meat. The former is the consequence of an excessively high rate of post mortem glycolysis which is clearly manifest in HP pigs when they are killed under minimal stress conditions and the latter appears to be unrelated to halothane sensitivity as the ultimate pH of HP and HN pigs is similar when the animals are slaughtered under stress conditions. PMID- 22054603 TI - Effects of breed and nutrition on the productive traits of Zebu, Charolais and crossbreed beef cattle in south-east Brazil- Part 1: Body and gross carcase composition. AB - A study of the effects of breed and nutrition on the productive traits of Nelore, Guzera, Charolais and Canchim cattle found in south-east Brazil was undertaken as part of an overall research programme to differentiate between carcase classes with a view to elaborating carcase classification proposals. The forty animals used in this study were divided into two treatment groups representing intensive and extensive feeding systems. Recovered data were analysed to determine the effects of breed, treatment and possible breed-treatment interaction on the proportions of internal and external offals and gross carcase composition. The results demonstrated that although some differences in carcase composition could be attributed to breed effect, most were caused by the varying nutrional status of the animals pre-slaughter. The Charolais-and, to a lesser extent, the Canchim animals-were seriously maladjusted to the harsh range conditions and showed lower daily liveweight gains and reduced liveweight at slaughter. The significantly lower special hindquarters and higher forequarter proportions in the Zebu animals were thought to be due to the cervical enlargement of the rhomboid muscle and earlier sexual maturity in the Bos indicus animals. PMID- 22054604 TI - Fibre types in Longissimus dorsi from wild and highly selected pig breeds. AB - Longissimus dorsi muscles from six pig breeds were examined histologically. It was found that mean fibre diameter increased with degree of selection in domestic pigs and that the percentage of red fibres decreased-i.e. from Mangulica and Black Slavonian to Large White and Swedish Landrace. The percentage of white fibres showed the reverse tendency whilst that of the intermediate type was not markedly changed. In semi-wild pigs, the percentage of red fibres was still higher and in forest pigs there were neither white nor intermediate fibres in longissimus dorsi. Beneath the sarcolemna of red fibres there was a significantly higher number of mitochondria than in the central parts of the fibre. The distribution of the 'giant fibres' indicated that this formation may be found in the muscles of both stress-susceptible and stress-insusceptible pigs. PMID- 22054605 TI - Cellular heterogeneity in the response of beef to electrical stimulation. AB - Strips of bovine sternomandibularis muscle were removed at slaughter and kept anoxic at body temperature. One strip of each pair was electrically stimulated with square wave pulses for 60 min (32 ms duration, 2Hz, <6 or 100V). Differences between stimulated and control strips were examined histochemically to determine the effect of stimulation on post-mortem glycogenolysis in different fibre types. Serial reactions for ATPase and SDH were used to type muscle fibres and the absorbance of PAS-stained glycogen was measured with a two-wavelength correction for distributional error. Relative to unstimulated control strips, fibres with strong ATPase and weak SDH reactions showed most glycogenolysis whilst fibres with weak ATPase and strong SDH reactions showed the least. Fibres with strong ATPase and strong to moderate SDH reactions showed an intermediate response. Half of the fibre populations examined had an initial increase in absorbance of PAS stained glycogen in some or all fibres. PMID- 22054606 TI - Basis for a method of characterization for quick frozen beef. AB - For better commercial development simple methods of quality control are needed to distinguish between quick frozen and normally frozen products. Usually the specifications for quick frozen meat have been limited to a description of the freezing process rather than to the establishment of quality standards which could be detected by tests on the product itself. In a previous paper a maximum in the weight of drip obtained on thawing was identified at local freezing times (-1 degrees C to -7 degrees C) of 17 min. The higher the freezing rate, the deeper the position of this maximum. Simultaneously, a computer model was developed to define the local freezing time and link it with an average freezing rate, through the simulation of heat transfer, during meat processing in plane freezers. On these bases a characterisation of quick frozen meat has been quantitatively developed in terms of the maximum position. PMID- 22054607 TI - Improved methodology for the electrophoretic determination of horse meat in heated foodstuffs. AB - Using linear gradient polyacrylamide gel electrophoresis to separate constituent proteins, horse meat could be clearly distinguished from beef even after heating for 20 min at up to 120 degrees C. PMID- 22054608 TI - Effects of early post-mortem pH and temperature on beef tenderness. AB - The tenderness of loin steaks, prepared from beef sides after chilling, is strongly influenced by muscle temperature in the first 3 h after slaughter. Maintenance of about 37 degrees C within the Longissimus muscle during this time, whether by heavy fat cover or by ambient-temperature manipulation, results in appreciable tenderness enhancement. Early post-mortem muscle pH (which varies over a wide range) also affects tenderness significantly; provided early and exceptionally fast chilling does not induce cold shortening, slow glycolysis promotes tenderness. Low-frequency (2 Hz) electrical stimulation, which accelerates glycolysis but causes negligible tissue disruption, significantly toughens the loin; in its normal mode (50-60 Hz), therefore, stimulation produces its desirable tenderising effect mainly-and perhaps solely-by fibre fracture. PMID- 22054610 TI - Corporate Sponsorship. PMID- 22054611 TI - Bacteriological quality assurance (BQA) of mechanically deboned meat (MDM). AB - Adequacy of bacteriological quality assurance during the commercial production of mechanically deboned meat (MDM) was assessed. Lax standards of hygiene during production were observed, resulting in high numbers of Staphylococcus aureus, viz. 10(4) to 10(5) cfu g(-1), and severe contamination with Enterobacteriaceae: 10(5) to 10(6) cfu g(-1). These data indicate that measures of hygiene observed during boning of carcasses and during collection, storage and transport of bones or poultry parts should be markedly tightened, while conditions of refrigerated storage of raw materials and MDM should be improved. Use of bones of poor sensory quality (discoloration, abnormal smell) generally resulted in MDM of inferior bacteriological quality. Phage typing, biotyping and assessment of enterotoxin production was carried out with 136 St. aureus cultures, isolates from mechanically deboned pork produced at one plant. Fifty-five per cent of the isolates was not typable, 28% was typable with human phages, 8% with bovine phages. The majority of the strains could not be explicitly assigned to any Meyer and/or Hajek and Marsalek types. Applying the simplified system of Devriese to eighteen strains isolated in our investigation, ten were found to belong to the poultry ecovar, one to the bovine ecovar, while seven strains were non-host specific. None of the isolates produced enterotoxins A-E. Microbiological inspection of end products is recommended as part of an integrated quality assurance system. The following reference values for the final product (maximal colony counts to be expected under GMP conditions expressed as 95th percentile) were calculated: Pig MDM: log(10) mesophilic colony count 6.8 and log(10) cfu mesophilic Enterobacteriaceae g(-1) 4.8; Poultry MDM: log(10) mesophilic colony count 6.6 and log(10) cfu mesophilic Enterobacteriaceae g(-1) 4.7. PMID- 22054612 TI - The effects of curing and cooking on the detection of species origin of meat products by competitive and indirect ELISA techniques. AB - The purposes of this study were: (1) to develop and compare competitive and indirect enzyme linked immunosorbent assay (ELISA) methods for detecting species specific albumins in meat samples and (2) to examine the effect of curing and cooking on the identification of species origin of meats. Commercially obtained rabbit anti-pig serum albumin (anti-PSA) and rabbit anti-sheep serum albumin (anti-SSA) were affinity purified, and used to develop competitive and indirect ELISA procedures for PSA and SSA. The competitive ELISA procedures showed the lowest cross-reactivity with related serum albumins. Both ELISA procedures were capable of detecting as little as 5% pork or sheep in beef. Curing resulted in little or no inhibition in the ability of ELISA procedures to detect pork or sheep in beef. Cooking completely eliminated the ability of the competitive PSA ELISA to detect pork in beef, and of both SSA ELISA procedures to detect sheep in beef. Cooking also greatly reduced, but did not eliminate, the ability of the indirect PSA ELISA to detect pork in beef. Curing and cooking essentially eliminated the ability of the PSA ELISA procedure to detect pork in beef. Curing and cooking resulted in a 70 to 74% decrease in the signal of sheep meat in SSA ELISA procedures. These results demonstrated that competitive and indirect ELISA procedures are capable of determining the species origin of raw and cured meat. Heating raw or cured meats greatly reduced, but did not always eliminate, the ability of ELISA procedures to detect species origin of meats. PMID- 22054613 TI - Marbling fat in beef. AB - The growth and distribution of intramuscular fat was studied in 62 carcases from four beef genotypes, Angus, Hereford, Friesian and Charolais x Illawarra. Relative to dissected side fat weight, ether extract weight of side muscle was deposited in a similar manner in all four genotypes. At high levels of side fatness (45 kg) Herefords had significantly less ether extract than the other genotypes. Ether extract percentage (of side muscle) was greater in the Angus than in the other genotypes at low side fatness levels (20 kg, 30 kg or 20%). Relative to dissected fat percentage ether extract percentage of side muscle, initially lower in the Friesians and Charolais x Illawarra than in the Angus and Herefords at low levels of carcase fatness, was not significantly different from them over 27% dissected fat. With increasing carcase fatness marbling fat was deposited differentially among the primal cuts, with few major between-breed differences. A study of the muscle weight distribution of the primal cuts confirmed the cutting technique as a useful method for examining the commercial importance of marbling. PMID- 22054614 TI - Factors associated with tenderness in young beef. AB - One hundred and twenty-two crossbred steers of varying percentages of Bos Indicus and Bos Taurus breeding were slaughtered to determine the relationship of carcass and meat characteristics to tenderness. Carcasses were graded and longissimus dorsi muscle samples were evaluated for fibre type characteristics, sensory and shear force determination, sarcomere length, intramuscular fat content, collagen content and solubility and fragmentation index. Sarcomere length and collagen content and solubility were not significantly related to shear force values or sensory tenderness ratings. The fragmentation index was highly correlated to sensory tenderness ratings (r = -0.60) and shear force values (r = 0.53) indicating that variation in tenderness is associated with myofibrillar protein degradation. A four variable regression equation that included fragmentation index, lean colour, marbling and per cent red fibres accounted for 56% of the variation in sensory tenderness. Fragmentation index directly accounted for 30% of the variation in sensory tenderness in the four variable equation. PMID- 22054615 TI - The effect of fasting on liveweight and carcass characteristics in lambs. AB - In two experiments, involving 250 and 300 lambs, respectively, lambs were fasted (with access to water) and slaughtered after 0, 1, 2, 3 and 4 days. The effects of initial fat score, initial liveweight and sex (wethers and ewes) on the patterns of loss in liveweight, hot carcass weight and carcass characters (fat depth at the GR and C sites, kidney fat weight and the weights of chemical carcass components) were examined. In experiment 2 the effects of weaning and transport on fasting losses were also examined. The rate of liveweight loss (expressed as a percentage of initial liveweight) was greater in the initial stages of the fast and was affected by fat score, with a greater loss in lambs with a lower fat score. The pattern of loss in hot carcass weight with fasting was curvilinear and in experiment 2 was affected by both fat score and liveweight, with leaner, heavier lambs having a greater loss. In experiment 2 the decrease in fat depth at the GR site interacted with fat score, with a greater loss in lambs with a lower fat score. Transport per se had no effect on hot carcass weight or carcass characteristics. PMID- 22054617 TI - Factors influencing outcome in patients undergoing portal vein resection for adenocarcinoma of the pancreas. AB - BACKGROUND: Survival rates after surgery and adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDA) remain low. Selected patients with portal/superior mesenteric vein (PV) involvement undergo PV resection at pancreaticoduodenectomy (PD). This study analyses outcomes for PD with/without PV resection in patients with PDA. METHODS: A retrospective analysis of prospectively collected data on patients requiring PD for histologically proven adenocarcinoma between 1/1997 and 9/2009 identified 326 patients with PDA, with 51 requiring PD with PV resection. Patients were analyzed in two groups: PD + PV resection vs. PD alone. Multivariate analysis was used to identify predictive variables influencing survival and the Kaplan-Meier method to estimate patient survival. RESULTS: Mean age for patients with PV resection was 66.4 (range 46-80) years, 47% were male. Both groups had similar patient demographics, perioperative and tumor characteristics. Postoperative morbidity was similar for patients with and without PV resection (27.5 vs. 28.4%). 30-day mortality was significantly higher in patients with PV resection (13.7%) vs. PD alone (5.1%). Overall survival however was similar in both groups (median PD alone 14.8 months vs. 14.5 months PD + PV). Multivariate analysis identified age, tumor grading, stay on the ICU and lack of chemotherapy as independent risk factors for reduced long-term survival. CONCLUSION: In carefully selected patients, PV resection results in similar long-term survival compared to PD alone. In selected patients, PV infiltration may be considered a sign of anatomical proximity of the tumor, rather than only a sign of increased tumor aggressiveness. PMID- 22054618 TI - Pseudopseudoseizures: conditions that may mimic psychogenic non-epileptic seizures. AB - BACKGROUND: Video electroencephalography (vEEG) has proven to be a valuable tool in the differentiation of pseudoseizures or psychogenic non-epileptic seizures (PNES) from epileptic seizures. Clinicians should, however, be aware of a number of conditions that may be misdiagnosed as pseudoseizures. OBJECTIVE: To review a number of somatic conditions that can present with disturbances of consciousness and unusual motor activity without epileptiform findings on vEEG. METHOD: We report a case of a young woman who presented with a number of neuropsychiatric symptoms, including episodic posturing and rhythmic movements. The absence of epileptiform findings on vEEG resulted in a diagnosis of conversion disorder with pseudoseizures. She was ultimately diagnosed with N-methyl-D-aspartate (NMDA) receptor autoimmune encephalitis (AIE) secondary to an ovarian tumor. AIE and other potential mimics of pseudoseizures are discussed. RESULTS: A number of somatic conditions can present with symptoms that may be misinterpreted as pseudoseizure. PMID- 22054619 TI - Primitive reflexes associated with delirium: a prospective trial. AB - BACKGROUND: The presence of primitive reflexes (PRs) may have diagnostic or prognostic value in the evaluation of cognitive impairment. OBJECTIVE: We hypothesized that the presence of preoperative PRs would predict the development of postoperative delirium and that the emergence of PRs postoperatively would be positively associated with the emergence of delirium. METHODS: Patients participating in a larger study on the prophylaxis of postoperative delirium were evaluated for the presence of six PRs (grasp reflex [left and right], palmomental reflex [left and right], glabellar tap, and snout reflex), preoperatively and postoperatively. The presence of PRs was then correlated with the development of delirium. RESULTS: Of the 79 patients studied, 29% (n = 23) developed delirium during the postoperative period. The preoperative presence of one PR did not predict the development of delirium, but the only patient with >1 PR preoperatively went on to develop delirium in the postoperative period. Similarly, having one frontal release sign in the postoperative period did not correlate with delirium, while the appearance of more than one PR was associated with a greater likelihood of delirium. Of the 11 patients who had two or more frontal release signs during one postoperative examination, six (55%) developed delirium. Of the five patients who showed three or more frontal release signs, 4 (80%) developed delirium. CONCLUSION: Our study is the first to investigate the relationship between the appearance of PRs and the development of delirium. We have provided some evidence that PRs are associated with acute CNS dysfunction. PMID- 22054620 TI - Proactive psychiatric consultation services reduce length of stay for admissions to an inpatient medical team. AB - BACKGROUND: Some studies suggest intensive psychiatric consultation services facilitate medical care and reduce length of stay (LOS) in general hospitals. OBJECTIVE: To compare LOS between a consultation-as-usual model and a proactive consultation model involving review of all admissions, rapid consultation, and close follow-up. METHODS: LOS was compared in an ABA design between a 33-day intervention period and 10 similar control periods, 5 before and 5 after the intervention, on an internal medical unit. During the intervention period, a staff psychiatrist met with the medical team each weekday, reviewed all admissions, provided immediate consultation as needed, and followed all cases throughout their hospital stay. RESULTS: Time required for initial case review was brief, 2.9 +/- 2.2 minutes per patient (mean +/- S.D.). Over 50% of admissions had mental health needs: 20.3% were estimated to require specialist consultation to avoid potential delay of discharge. The consultation rate for the intervention sample was 22.6%, significantly greater than in the control sample, 10.7%. Mean LOS was significantly shorter in the intervention sample, 2.90 +/- 2.12 versus 3.82 +/- 3.30 days, and the fraction of cases with LOS > 4 days was significantly lower, 14.5% versus 27.9%. A rough cost benefit analysis was favorable with at least a 4.2 ratio of financial benefit to cost. CONCLUSIONS: Psychiatric review of all admissions is feasible, indicates a high incidence of mental health barriers to discharge, identifies more necessary consultations than typically requested, and results in earlier consultation. A proactive consultation model can reduce hospital LOS. PMID- 22054621 TI - Documentation of decision-making capacity, informed consent, and health care proxies: a study of surrogate consent. AB - BACKGROUND: Patients in the general hospital are routinely asked to make decisions about their medical care. However, some of them are unable to express a choice, understand the information provided, weigh the options, or make a decision for themselves; when this occurs, the task of making an appropriate medical decision is left to another-a substitute decision-maker (SDM). OBJECTIVE: We sought to understand the practice patterns surrounding surrogate consent. We hypothesized that SDMs would be used frequently for patients with an altered mental status (AMS) but that there would be insufficient documentation of health care proxies (HCP) and of clinician assessment of a patient's decision-making capacity. METHODS: A retrospective chart review was conducted on inpatients who underwent a lumbar puncture. The review assessed whether patients had a HCP in the record, if the patient's mental status was evaluated prior to obtaining informed consent, if the patient's capacity was addressed in this assessment, and whether a SDM was asked to provide the informed consent. RESULTS: Consistent with our hypotheses, we found that the majority of patients did not have documentation of a HCP in the record. We found that the mental status of all patients was assessed prior to the procedure, but that documentation regarding assessment of decision-making capacity was lacking. CONCLUSIONS: Our pilot investigation suggests that there is need for improvement in our evaluation and documentation of altered mental status and a patient's ability to make informed decisions. To this end, several quality-improvement suggestions are discussed. PMID- 22054622 TI - Psychiatry resident education in palliative care: opportunities, desired training, and outcomes of a targeted educational intervention. AB - OBJECTIVES: To assess the educational offerings provided to psychiatry residents in palliative care as well as their concomitant interest in learning more about this subspecialty. To measure the pre- and post-levels of competence, concern, and knowledge exhibited by psychiatry residents when completing a formalized clinical rotation in hospice and palliative care, with additional comparisons to family and internal medicine residents completing the same clinical rotation. METHODS: Fifty-two Psychiatry Program Directors and 98 psychiatry residents completed an online survey assessing the current course offerings and level of interest in palliative care. Thirty psychiatry residents were additionally evaluated before and after completion of a clinical rotation in hospice and palliative care. RESULTS: Few programs offered any formalized training in palliative care, although nearly all psychiatry residents reported interest in this area. A clinical rotation in palliative care significantly increased psychiatry residents' competence and knowledge while simultaneously decreasing their concerns about practice in this area; most were at levels comparable to family and internal medicine residents completing the same rotation. Psychiatry residents' knowledge of pain assessment, pain management, and generalized non pain management were also enhanced during the rotation. CONCLUSIONS: Results indicate that training opportunities in palliative care are lacking for psychiatry residents in the United States although residents report strong interest in this area. This study finds psychiatry residents can benefit as much as other disciplines from receiving palliative care training. The need to offer such training within psychiatry residencies is highlighted and the welcoming of psychiatrists into palliative care is suggested. PMID- 22054623 TI - Practice and career outcomes of double-boarded psychiatrists. AB - BACKGROUND: The practice patterns and career paths of physicians who are double boarded in medicine, family practice, or neurology and psychiatry are not well understood. Given increased attention to integrated medical and psychiatric care, these individuals may play an important role. OBJECTIVE: To compare the practice patterns and career paths of physicians who are double-boarded in medicine, family practice, or neurology and psychiatry with physicians who are boarded in general psychiatry, and among double-boarded physicians with various training sequences and specialty types. METHOD: A survey was distributed to all physicians identified by the American Board of Medical Specialties (ABMS) as double-boarded in medicine, family practice, or neurology and psychiatry, and an equal number of physicians who are boarded in general psychiatry. RESULTS: Compared with psychiatrists who are not double-boarded, double-boarded psychiatrists are significantly more likely to be older, more likely to be male, to practice in consultation-liaison or inpatient settings, and to assume positions of leadership in departments of psychiatry or in general health care organizations. Among the various groups of double-boarded physicians, 39% continue to practice their medical specialty in addition to their psychiatry practice, although this varies by medical specialty, sequence or type of program, and motivation for double board training. CONCLUSION: Double-boarded physicians appear to be a distinct group within psychiatry and may serve as an important bridge to the general medical environment because of their leadership roles and medical psychiatric practice patterns. Further understanding of their career development and roles is warranted. PMID- 22054624 TI - Dream anxiety is an emotional trigger for acute myocardial infarction. AB - OBJECTIVE: The aim of the present study was to investigate the relationship between nightmares and acute myocardial infarction (AMI) occurring during sleep, and also to evaluate the influence of several related factors. METHOD: The sample comprised AMI patients who had been admitted to the coronary care unit. The patients were grouped into two categories; the asleep-AMI group consisted of 36 patients who had the onset of symptoms of AMI during sleep, and the awake-AMI group included 183 patients who had AMI while they were awake. The sleep quality and dream anxiety for the 1-month interval before AMI were assessed with Pittsburgh Sleep Quality Index (PSQI) and Van Dream Anxiety Scale (VDAS), respectively. RESULTS: Asleep-AMI patients reported significantly poorer subjective sleep quality, significantly higher global PSQI scores, and displayed significantly higher nightmare frequency, difficulty in falling asleep after a nightmare, higher autonomic hyperactivity, dream recall frequency, daytime anxiety, psychological problems, and higher global dream anxiety scores than awake-AMI patients. CONCLUSION: The present study suggests that sleep anxiety and related emotions are associated with AMI during sleep. PMID- 22054625 TI - Psychobiological changes from relaxation response elicitation: long-term practitioners vs. novices. AB - OBJECTIVE: The relaxation response (RR) is a physiological state that is the counterpart to the stress response. We investigate the psychological and biological effects, as well as the correlation between these two effects that are associated with short-term vs. long-term practice of techniques that elicit the RR ("RR practice"). METHODS: The study comprised both a cross sectional and an 8 week prospective design. The study sample included individuals with a long-term RR practice ("long-term practitioners" n = 28) and those with no prior RR practice experience ("novices" n = 28). The novices received 8 weeks of RR elicitation training ("RR training") for the prospective analysis (short-term practice). RESULTS: Long-term practitioners reported lower levels of psychological distress than the novices before they received RR training. As a result of the 8-week RR training, novices significantly reduced their psychological distress to levels comparable to that of long-term practitioners. Long-term practitioners had greater immediate (after listening to a RR-eliciting CD) decreases in psychological distress level than the 8-week trained novices. Furthermore, the reduction in psychological distress levels for long-term practitioners correlated with a reduction in biological measures of stress, after controlling for baseline values. There was no reduction in biological measures and no correlation with psychological measures in the 8-week trained novices. CONCLUSIONS: While our data indicate that even a short-term 8-week RR-eliciting practice can decrease psychological distress levels, only after years of RR practice does psychological distress reduction coincide with biological change. PMID- 22054626 TI - "Playing possum:" differential diagnosis, work-up, and treatment of profound interpersonal withdrawal. PMID- 22054627 TI - A case of utilization behavior and hyperorality following bilateral anterior cerebral artery infarct partially responsive to carbamazepine: can both behaviors be attributed to lesions in different frontal lobe circuits? PMID- 22054628 TI - Paraneoplastic encephalitis presenting as postpartum psychosis. PMID- 22054629 TI - Cotard syndrome in semantic dementia. PMID- 22054630 TI - Klinefelter's syndrome in a 5-year-old boy with behavioral disturbances and seizures. PMID- 22054631 TI - "Ephedra-free" diet pill-induced psychosis. PMID- 22054632 TI - Severe INR elevation related to duloxetine use: a case report. PMID- 22054633 TI - Bath salt abuse: neuropsychiatric effects of cathinone derivatives. PMID- 22054634 TI - Moving beyond unexplained medical symptoms in DSM-5: great idea, problematic execution. PMID- 22054635 TI - Is gait preoccupation a type of body dysmorphic disorder? A case report and a diagnostic question for DSM-V. PMID- 22054636 TI - Psychosocial risk factors for hospital readmission in COPD patients on early discharge services: a cohort study. AB - BACKGROUND: Hospital readmission for acute exacerbation of COPD (AECOPD) occurs in up to 30% of patients, leading to excess morbidity and poor survival. Physiological risk factors predict readmission, but the impact of modifiable psychosocial risk factors remains uncertain. We aimed to evaluate whether psychosocial risk factors independently predict readmission for AECOPD in patients referred to early discharge services (EDS). METHODS: This prospective cohort study included 79 patients with AECOPD cared for by nurse led EDS in the UK, and followed up for 12 months. Data on lung function, medical comorbidities, previous hospital admissions, medications, and sociodemographics were collected at baseline; St George's Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS), and social support were measured at baseline, 3 and 12 months. Exploratory multivariate models were fitted to identify psychosocial factors associated with readmission adjusted for known confounders. RESULTS: 26 patients were readmitted within 90 days and 60 patients were readmitted at least once during follow-up. Depression at baseline predicted readmission adjusted for sociodemographics and forced expiratory volume in 1 second (odds ratio 1.30, 95% CI 1.06 to 1.60, p = 0.013). Perceived social support was not significantly associated with risk of readmission. Home ownership was associated with the total number of readmissions (B = 0.46, 95% CI -0.86 to -0.06, p = 0.024). Compared with those not readmitted, readmitted patients had worse SGRQ and HADS scores at 12 months. CONCLUSION: Depressive symptoms and socioeconomic status, but not perceived social support, predict risk of readmission and readmission frequency for AECOPD in patients cared for by nurse-led EDS. Future work on reducing demand for unscheduled hospital admissions could include the design and evaluation of interventions aimed at optimising the psychosocial care of AECOPD patients managed at home. PMID- 22054637 TI - Cost per quality-adjusted life year gained of laminectomy and extension of instrumented fusion for adjacent-segment disease: defining the value of surgical intervention. AB - OBJECT: Over the past decade, there has been a dramatic increase in the number of spinal fusions performed in the US and a corresponding increase in the incidence of adjacent-segment disease (ASD). Surgical management of symptomatic ASD consists of decompression of neural elements and extension of fusion. It has been shown to have favorable long-term outcomes, but the cost-effectiveness remains unclear. In this study, the authors set out to assess the cost-effectiveness of revision surgery in the treatment of ASD over a 2-year period. METHODS: Fifty patients undergoing neural decompression and extension of fusion construct for ASD-associated back and leg pain were included in the study. Two-year total back related medical resource utilization, missed work, and health state values (quality-adjusted life years [QALYs], calculated from the EQ-5D with US valuation) were assessed. Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts (direct cost), and patient and caregiver workday losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). Mean total 2-year cost per QALY gained after revision surgery was assessed. RESULTS: The mean (+/- SD) interval between prior fusion and revision surgery for ASD was 3.07 +/- 2.02 years. A mean cumulative 2-year gain of 0.76 QALYs was observed after revision surgery. The mean total 2-year cost of extension of fusion constructs was $47,846 +/- $32,712 (surgery cost: $24,063 +/- $300; outpatient resource utilization cost: $4175 +/- $3368; indirect cost: $19,607 +/- $32,187). Revision decompression and extension of fusion was associated with a mean 2-year cost per QALY gained of $62,955. CONCLUSIONS: In the authors' practice, revision decompression and extension of fusion provided a significant gain in health state utility for patients with symptomatic ASD, with a 2-year cost per QALY gained of $62,995. When indicated, revision surgery for ASD is a valuable treatment option for patients experiencing back and leg pain secondary to ASD. The findings provide a value measure of surgery that can be compared with future cost-per-QALY-gained studies of medical management or alternative surgical approaches. PMID- 22054638 TI - Avoidance of wrong-level thoracic spine surgery: intraoperative localization with preoperative percutaneous fiducial screw placement. AB - OBJECT: The accurate intraoperative localization of the correct thoracic spine level remains a challenging problem in both open and minimally invasive spine surgery. The authors describe a technique of using preoperatively placed percutaneous fiducial screws to localize the area of interest in the thoracic spine, and they assess the safety and efficacy of the technique. METHODS: To avoid wrong-level surgery in the thoracic spine, the authors preoperatively placed a percutaneous 5-mm fiducial screw at the level of intended surgery using CT guidance. Plain radiographs and CT images with reconstructed views can then be referenced in the operating room to verify the surgical level, and the fiducial screw is easily identified on intraoperative fluoroscopy. The authors compared a group of 26 patients who underwent preoperative (often outpatient) fiducial screw placement prior to open or minimally invasive thoracic spine surgery to a historical group of 26 patients who had intraoperative localization with fluoroscopy alone. RESULTS: In the treatment group of 26 patients, no complications related to fiducial screw placement occurred, and there was no incidence of wrong-level surgery. In comparison, there were no wrong-level surgeries in the historical cohort of 26 patients who underwent mini-open or open thoracic spine surgery without placement of a fiducial screw. However, the authors found that the intraoperative localization fluoroscopy time was greatly reduced when a fiducial screw localization technique was employed. CONCLUSIONS: The aforementioned technique for intraoperative localization is safe, efficient, and accurate for identifying the target level in thoracic spine exposures. The fiducial marker screw can be placed using CT guidance on an outpatient basis. There is a reduction in the amount of intraoperative fluoroscopy time needed for localization in the fiducial screw group. PMID- 22054639 TI - Cost per quality-adjusted life year gained of revision neural decompression and instrumented fusion for same-level recurrent lumbar stenosis: defining the value of surgical intervention. AB - OBJECT: Despite advances in technology and understanding in spinal physiology, reoperation for symptomatic same-level recurrent stenosis continues to occur. Although revision lumbar surgery is effective, attention has turned to the question of the utility and value of revision decompression and fusion procedures. To date, an analysis of cost and heath state gain associated with revision lumbar surgery for recurrent same-level lumbar stenosis has yet to be described. The authors set out to assess the 2-year comprehensive cost of revision surgery and determine its value in the treatment of same-level recurrent stenosis. METHODS: Forty-two patients undergoing revision decompression and instrumented fusion for same-level recurrent stenosis-associated leg and back pain were included in this study. Two-year total back-related medical resource utilization, missed work, and health state values (quality-adjusted life years [QALYs], calculated from the EQ-5D with US valuation) were assessed. Two-year resource use was multiplied by unit costs based on Medicare national allowable payment amounts (direct cost), and patient and caregiver workday losses were multiplied by the self-reported gross-of-tax wage rate (indirect cost). Mean total 2-year cost per QALY gained after revision surgery was assessed. RESULTS: The mean (+/- SD) interval between prior and revision surgery was 4.16 +/- 4.64 years. Bone morphogenetic protein was used in 7 cases of revision arthrodesis (16.7%). A mean cumulative 2-year gain of 0.84 QALY was observed after revision surgery. The mean total 2-year cost of revision fusion was $49,431 +/- $7583 (surgery cost $21,060 +/- $4459; outpatient resource utilization cost $9748 +/- $5292; indirect cost $18,623 +/- $9098). Revision decompression and extension of fusion was associated with a mean 2-year cost per QALY gained of $58,846. CONCLUSIONS: In the authors' practice, revision decompression and fusion provided a significant gain in health state utility for patients with symptomatic same level recurrent stenosis, with a 2-year cost per QALY gained of $58,846. When indicated, revision surgery for same-level recurrent stenosis is a valuable treatment option for patients experiencing back and leg pain secondary to this disease. The authors' findings provide a value measure of surgery that can be compared with the results of future cost-per-QALY-gained studies of medical management or alternative surgical approaches. PMID- 22054640 TI - Letter to the editor: electromyography and breached screws. PMID- 22054641 TI - EEG oscillatory states as neuro-phenomenology of consciousness as revealed from patients in vegetative and minimally conscious states. AB - The value of resting electroencephalogram (EEG) in revealing neural constitutes of consciousness (NCC) was examined. We quantified the dynamic repertoire, duration and oscillatory type of EEG microstates in eyes-closed rest in relation to the degree of expression of clinical self-consciousness. For NCC a model was suggested that contrasted normal, severely disturbed state of consciousness and state without consciousness. Patients with disorders of consciousness were used. Results suggested that the repertoire, duration and oscillatory type of EEG microstates in resting condition quantitatively related to the level of consciousness expression in brain-damaged patients and healthy-conscious subjects. Specifically, results demonstrated that (a) decreased number of EEG microstate types was associated with altered states of consciousness, (b) unawareness was associated with the lack of diversity in EEG alpha-rhythmic microstates, and (c) the probability for the occurrence and duration of delta-, theta- and slow-alpha-rhythmic microstates were associated with unawareness, whereas the probability for the occurrence and duration of fast-alpha-rhythmic microstates were associated with consciousness. In conclusion, resting EEG has a potential value in revealing NCC. This work may have implications for clinical care and medical-legal decisions in patients with disorders of consciousness. PMID- 22054642 TI - Creating a quality of life assessment measure for residents in long term care. AB - OBJECTIVES: The objectives of this study were to (1) gain an empirical understanding of how stakeholder (residents, family members, staff) groups view quality of life (QoL) for residents in long term care; (2) create a visual map of the domain of QoL and describe differences in importance of key elements; and (3) identify key elements of QoL that could be used to develop a standardized assessment instrument for use in person-centered care planning. DESIGN: This is a descriptive study, using a mixed-method, qualitative/quantitative approach called "concept mapping." SETTING: The study was conducted at a 240-bed skilled nursing facility located in a major metropolitan area. It is part of a not-for-profit religiously affiliated social service organization. PARTICIPANTS: A convenience sample included 3 groups of participants: staff members, family members of residents, and residents. Fifty-three people participated in the brain-storming sessions, and 45 people completed sorting and rating tasks. Sample sizes varied by group and by task. MEASUREMENTS: Statements about the elements of QoL for residents in long term care were elicited during 14 brain-storming sessions. Sorting and rating activities were completed using a final list of 88 items. RESULTS: A visual map was generated, with 5 clusters of elements representing 5 conceptual areas within QoL. Importance ratings of elements were similar for family members and staff members, and a set of elements rated as high in importance but requiring attention to implementation was produced. CONCLUSIONS: Family members and staff produced similar conceptual models of QoL, and their views on the importance of the various elements were consistent. There was a high degree of consensus regarding elements considered least important and those considered most important. Elements considered most important addressed quality of care, autonomy and respect, and aspects of daily life, including food and sleep. There was less concern with the physical appearance of the facility, the amenities offered, and issues related to independence; however, all items scored above the mean of 2.5 on the 5-point rating scale. This project has shown that it is possible to use concept mapping methodology to obtain facility-specific information about stakeholders' QoL perceptions in the long term care setting, and that residents' views can be assessed and incorporated. PMID- 22054643 TI - High throughput screening with chlorophyll fluorescence imaging and its use in crop improvement. AB - Marker assisted plant breeding is a powerful technique for targeted crop improvement in horticulture and agriculture. It depends upon the correlation of desirable phenotypic characteristics with specific genetic markers. This can be determined by statistical models that relate the variation in the value of genetic markers to variation in phenotypic traits. It therefore depends upon the convergence of three technologies; the creation of genetically characterised (and thus marked) populations, high throughput screening procedures, and statistical procedures. While a large number of high throughput screening technologies are available, real-time screening techniques are usually based on some kind of imaging technologies, such as chlorophyll fluorescence imaging, that offers physiological data that are eminently suitable as a quantitative trait for genetic mapping. PMID- 22054644 TI - Toward nitrogen neutral biofuel production. AB - Environmental concerns and an increasing global energy demand have spurred scientific research and political action to deliver large-scale production of liquid biofuels. Current biofuel processes and developing approaches have focused on closing the carbon cycle by biological fixation of atmospheric carbon dioxide and conversion of biomass to fuels. To date, these processes have relied on fertilizer produced by the energy-intensive Haber-Bosch process, and have not addressed the global nitrogen cycle and its environmental implications. Recent developments to convert protein to fuel and ammonia may begin to address these problems. In this scheme, recycling ammonia to either plant or algal feedstocks reduces the demand for synthetic fertilizer supplementation. Further development of this technology will realize its advantages of high carbon fixation rates, inexpensive and simple feedstock processing, in addition to reduced fertilizer requirements. PMID- 22054646 TI - Effects of electrical stimulation on post-mortem changes in the activities of two Ca dependent neutral proteinases and their inhibitor in beef muscle. AB - Post-mortem changes in the activities of two calcium-dependent neutral proteinases and their inhibitor were studied in electrically stimulated and control beef Longissimus dorsi muscles. During meat conditioning in control muscles the activity of the high-calcium-requiring proteinase (mmCa ANP) was not affected while a decrease in the activities of the low-calcium-requiring proteinase (MUmCa ANP) was observed. After electrical stimulation, the mmCa ANP activity was only slightly decreased, but the MUmCa ANP and the inhibitor activities were drastically affected. An 80% decrease in MUmCa ANP activity was observed 4 h post electrical stimulation. The post-mortem changes seem to be closely related to the post-mortem pH fall. If the Ca-requiring neutral proteinases are involved in the meat ageing mechanism, it eems that the MUmCa ANP is more likely to cause most of the post-mortem changes in the myofibrillar proteins, taking into account the low level of intracellular calcium. But as its activity is drastically reduced during the rigor mortis process, most of the effect of MUmCa ANP could occur at the very beginning of the post-mortem changes. PMID- 22054645 TI - Specific involvement of atypical PKCzeta/PKMzeta in spinal persistent nociceptive processing following peripheral inflammation in rat. AB - BACKGROUND: Central sensitization requires the activation of various intracellular signalling pathways within spinal dorsal horn neurons, leading to a lowering of activation threshold and enhanced responsiveness of these cells. Such plasticity contributes to the manifestation of chronic pain states and displays a number of features of long-term potentiation (LTP), a ubiquitous neuronal mechanism of increased synaptic strength. Here we describe the role of a novel pathway involving atypical PKCzeta/PKMzeta in persistent spinal nociceptive processing, previously implicated in the maintenance of late-phase LTP. RESULTS: Using both behavioral tests and in vivo electrophysiology in rats, we show that inhibition of this pathway, via spinal delivery of a myristoylated protein kinase C-zeta pseudo-substrate inhibitor, reduces both pain-related behaviors and the activity of deep dorsal horn wide dynamic range neurons (WDRs) following formalin administration. In addition, Complete Freund's Adjuvant (CFA)-induced mechanical and thermal hypersensitivity was also reduced by inhibition of PKCzeta/PKMzeta activity. Importantly, this inhibition did not affect acute pain or locomotor behavior in normal rats and interestingly, did not inhibited mechanical allodynia and hyperalgesia in neuropathic rats. Pain-related behaviors in both inflammatory models coincided with increased phosphorylation of PKCzeta/PKMzeta in dorsal horn neurons, specifically PKMzeta phosphorylation in formalin rats. Finally, inhibition of PKCzeta/PKMzeta activity decreased the expression of Fos in response to formalin and CFA in both superficial and deep laminae of the dorsal horn. CONCLUSIONS: These results suggest that PKCzeta, especially PKMzeta isoform, is a significant factor involved in spinal persistent nociceptive processing, specifically, the manifestation of chronic pain states following peripheral inflammation. PMID- 22054647 TI - Variation in light scattering and water-holding capacity along the porcine Longissimus dorsi muscle. AB - The meat quality of M. longissimus muscle was evaluated in 851 pigs by using the Fibre Optic Probe (FOP) at three sites in the muscle and in both halves of the carcass. A systematic difference between sites was found, with the lowest light scattering (indicating the best meat quality) in the mid-part of the muscle and higher light scattering in the anterior and posterior parts. A non-systematic variation was also observed, with the opposite pattern in some animals, even though it was not frequent. A negative influence of the shackling was found, yielding higher FOP values in the shackled half. Drip loss measurements in the Longissimus muscle, taken from another 100 pig carcasses, were evaluated using three methods. Drip loss, too, showed a considerable variation along the Longissimus muscle, with minimum losses around the last rib. Repeatability estimates, calculated from two non-consecutive pieces of the Longissimus dorsi muscle from each carcass, varied from 0.4 when keeping samples vacuum packed for 2 days, to 0.5 when the samples were either kept in plain plastic bags for 2 days or in a meat container with a squared inset for 1 or 2 days. PMID- 22054648 TI - Methodology for meat species identification: A review. AB - This review covers methods available for the recognition of the species of animal whose meat is present in raw materials or meat products. Isolation of species specific proteins is cumbersome; however, isoelettric focusing followed by recognition of the pattern of protein bands is particularly effective for speciation. Immunoassay has been established as a powerful technique for the determination of food protein analytes in suitable extracts of unresolved mixtures. Simple immunodiffusion using antisera to serum proteins is sufficient to provide a check on the identity of suspect raw samples; routine control would involve extensive sampling programmes. Enzyme-linked immunosorbent assay procedures are also appropriate, but attempts to quantify individual meat species in mixtures have not been successful due to the variability of residual blood levels. Species identification in heat-processed meat products is hindered by progressive denaturation of the protein markers, leading to loss of solubility and antigenicity; the effects of heating can be minimised by a judicious choice of analyte and its solubilisation by renaturation. PMID- 22054649 TI - Nuclear magnetic resonance measurements on pork of various qualities. AB - Nuclear magnetic resonance measurements were made on pork samples from pigs of various genetic types (Large White, halothane positive and halothane-negative Pietrain) slaughtered either under minimal stress or somewhat stressful conditions. The (1)H spin-lattice (T(1)) and spin-spin (T(2)) relaxation times of water protons were recorded. The observed T(1) was single-exponential but a two component T(2) relaxation behaviour (components referred to as T(2a) and T(2b)) was observed. Highly significant relationships were found between T(1) and all the meat characteristics studied. T(2a) was related only to ultimate pH and cooking loss, whereas T(2b) was more closely related to the rate of post-mortem pH fall and protein denaturation criteria. PMID- 22054650 TI - Palatability characteristics of loin steaks from Charolais crossbred bulls and steers. AB - Loins from 1 2 - blood or 3 4 - to 7 8 - blood Charolais bulls (n = 60) and steers (n = 64) were obtained at 24 h post mortem from electrically stimulated sides and, at 12 days post mortem, steaks were removed and frozen. Shear force values were higher (P < 0.001) and sensory panel evaluations of tenderness and overall palatability were lower (P < 0.001) for steaks from bulls than from steers. No differences (P > 0.05) in connective tissue amount or off-flavour were detected for steaks from bulls versus steers. Significant correlations between carcass secondary sex characteristics and sensory panel evaluations of tenderness were noted, but the coefficients were not of a magnitude to be considered predictive of tenderness. PMID- 22054651 TI - The effect of high and low voltage electrical stimulation on beef quality. AB - Meat bulls were assigned to three treatment groups-high voltage intermittent electrical stimulation, low voltage electrical stimulation and no stimulation. Both stimulation methods resulted in a significantly more rapid pH fall in the longissimus and adductor muscles during the first 8 h post mortem. Carcass cooling rates were relatively slow, since temperatures of the longissimus and adductor muscles were 15 degrees C, respectively, at 8 h post mortem. Samples of stimulated longissimus, cut at 24h post mortem and vacuum stored at 3 degrees C for 6 days, had a brighter red colour, higher drip and heating loss, lower shear force values and scored better in taste panels, compared with samples from control carcasses. No significant differences were observed between high and low voltage electrical stimulation in quality traits measured. Although the combined result of pH and temperature measurements during the first 8 h post mortem suggest an absence of cold shortening conditions in control carcasses, a lower sarcomere length was found in samples of the longissimus muscle taken from these carcasses at 24 h post mortem. PMID- 22054652 TI - Novel small-caliber vascular grafts with trimeric Peptide for acceleration of endothelialization. AB - BACKGROUND: Both rapid endothelialization and the prevention of intimal hyperplasia are essential to improve the patency of small-caliber vascular grafts (SCVGs). Using the peptide array based screening system, we identified the peptide CAG (cysteine-alanine-glycine), which has a high affinity for endothelial cells and a low adhesive property for smooth muscle cells (SMCs). In this article, we report an in vivo analysis of novel vascular grafts that were constructed with a biodegradable polymer (poly-epsilon-caprolactone [PCL]) containing CAG peptide. METHODS: The novel SCVG, which measured 0.7 mm in diameter and 7 mm in length, was fabricated using the electrospinning technique. Carotid arterial replacement was performed on Sprague-Dawley rats using SCVGs with (group CAG) or without CAG (group C). Histologic and biochemical assessments were performed at 1, 2, and 6 weeks after implantation. RESULTS: The ratio of endothelialization was significantly higher in group CAG compared with group C (CAG versus C, 64.4+/-20.0% versus 42.1+/-8.9% at 1 week; p=0.017; 98.2+/-2.3% versus 72.7+/-12.9% at 2 weeks; p=0.001; and 97.4+/-4.6% versus 76.7+/-5.4% at 6 weeks; p<0.001). Additionally, Western blot analysis showed that the level of endothelial nitric oxide synthase (eNOS) at 1 week in group CAG was significantly higher than that in group C (CAG versus C, 1.20+/-0.37 versus 0.34+/-0.16; p=0.013), and that alpha-smooth muscle actin (ASMA) at 6 weeks in group CAG was significantly lower than that in group C (CAG versus C, 0.89+/-0.06 versus 1.25+/ 0.22; p=0.04). CONCLUSIONS: The graft with CAG promoted rapid endothelialization and the potential for inhibition of intimal hyperplasia. PMID- 22054653 TI - Abdominal aorta aneurysms in children: single-center experience of six patients. AB - BACKGROUND: Abdominal aortic aneurysms (AAA) are rare in children and are associated with significant morbidity and mortality as in adults. We summarize our experience in the diagnosis and management of AAAs in 6 children at a single institution. METHODS: The clinical data of 6 pediatric patients with AAAs treated at our hospital from November 2005 to November 2008 were retrospectively analyzed. RESULTS: There were 4 males and 2 females with a mean age at diagnosis of 8 years (range, 17 months to 18 years). All patients presented with pulsatile abdominal masses. Color Doppler ultrasonography and computed tomography angiography were the primary diagnostic tools. One patient has a history of tuberous sclerosis, and 1 had Takayasu's arteritis; no risk factors or identifiable causes were found in the other patients. All of the AAAs identified were infrarenal. Surgical reconstruction with aneurysm resection and prosthetic graft placement was performed successfully in all 6 cases. No intraoperative or postoperative complications occurred. Mean follow-up has been 48 months (range, 32 to 69). In 1 patient, recurrence was noted at 3 years postoperatively. The patient's family declined further surgery, and the patient died, likely of rupture of the aneurysm at 41 months postoperatively. All other patients are currently alive and well. CONCLUSIONS: Our experience indicates that good outcomes can be obtained in children with AAAs with prompt and accurate diagnosis and surgical management with artificial grafts. PMID- 22054654 TI - In situ replacement for mycotic aneurysms on the thoracic and abdominal aorta using rifampicin-bonded grafting and omental pedicle grafting. AB - BACKGROUND: The objective of this report is to discuss the efficacy of in situ replacement for treating mycotic aneurysm, particularly using rifampicin-bonded grafts and omental pedicle grafts, on the basis of our 7 years of experience. METHODS: Between December 2003 and December 2010, we performed surgical treatments in 23 patients (for the thoracic aorta in 6 patients, for the thoracoabdominal aorta in 8 patients, and for the abdominal aorta in 9 patients; 7 emergency, 10 urgent, and 6 elective operations) with mycotic aneurysm by using rifampicin-bonded grafting and omental pedicle grafting. RESULTS: One patient died in hospital because of local recurrent infection. One patient required an additional operation on another aortic site, and 3 patients had spinal cord injuries (2 transient and 1 permanent). Overall survival at 5 years was 95%, and the rate of freedom from aortic events at 5 years was 86%. CONCLUSIONS: In situ replacement using rifampicin-bonded grafting and omental pedicle grafting is effective for treating mycotic aneurysms of the thoracic and abdominal aorta. PMID- 22054655 TI - Long-term outcome for the surgical treatment of infective endocarditis with a focus on intravenous drug users. AB - BACKGROUND: We reviewed our experience with surgical procedures for infective endocarditis (IE) in order to evaluate modern outcomes and objectively examine our institutional preferences, including the use of bioprostheses in intravenous drug users (IVDUs) regardless of age and prompt surgical intervention in patients with either septic cerebral emboli or active infection. METHODS: Review of medical records was conducted from February 1999 to November 2010. The Social Security Death Index was used to determine death from any cause in the postoperative period. Hospital records were used to identify infectious complications, recurrent endocarditis, and reoperation. RESULTS: Sixty-four patients were identified as IVDUs and 133 patients as non-IVDUs. Survival at 30 days, 1 year, 5 years, and 10 years for IVDUs and non-IVDUs was 91.2% versus 93.6%, 77.5% versus 83.0%, 46.7% versus 71.1%, and 41.1% versus 52.0%, respectively. Cox regression analysis identified intravenous drug use as an independent risk factor for diminished survival (p=0.03), although not for reoperation (p=0.95) despite 95.3% of IVDUs receiving bioprostheses versus 73.7% of non-IVDUs (p=0.0002, Fisher's exact test). Forty-three patients were identified as having preoperative septic cerebral emboli; none had a perioperative hemorrhagic event. Active infection approached significance as an independent risk factor for the composite end point of recurrent IE and perioperative infection (odds ratio 2.8; 95% confidence interval, 0.777 to 10.9; p=0.12, Fisher's exact test). CONCLUSIONS: Bioprostheses are reasonable for IVDUs undergoing valve replacement for IE regardless of age. Prompt surgical intervention in the setting of septic cerebral emboli is justified; in the setting of active infection it is less clear. PMID- 22054656 TI - High-dose tranexamic acid is an independent predictor of early seizure after cardiopulmonary bypass. AB - BACKGROUND: Risk factors associated with early seizure after cardiopulmonary bypass (CPB) were examined. The role of tranexamic acid in seizure development was evaluated. METHODS: Early seizure was defined as a seizure occurring within 24 hours of CPB, without neurologic deficit or new lesion on brain imaging. Independent determinants of early seizure were examined by multivariate logistic regression modelling. RESULTS: Between 2004 and 2009, early seizure occurred in 119 of 8,929 patients (1.3%). A significant increase in the yearly rate of early seizure was observed in 2004 (0.73%) vs 2009 (1.97%; p<0.0001). Multivariate analysis showed the following variables were independent predictors of early seizure: age older than 75 years (adjusted odds ratio [OR], 2.1; p=0.0001), open heart procedure (OR, 12.0; p<0.0001), preoperative renal failure (OR, 3.2; p<0.0001), peripheral vascular disease (OR, 1.8; p=0.02), and total tranexamic acid dose of 100 mg/kg or more (OR, 2.6; p<0.0001). Risk of seizure was related to tranexamic acid in a dose-dependent fashion, with higher doses associated with increased risk of seizure. The use of CO2 in a subset of patients undergoing open heart procedures did not decrease the incidence of early seizure (4.8% vs 2.5% for no CO2; p=0.27). Postoperative chest tube drainage and blood product use were similar between patients receiving low-dose and high-dose tranexamic acid. CONCLUSIONS: High-dose tranexamic acid (>=100 mg/kg) is independently associated with an increased risk of early seizure. Future tranexamic acid trials should assess the blood-conserving effect of tranexamic acid at a lower dosage and specifically monitor for seizure occurrence. PMID- 22054657 TI - Subclinical changes in serum creatinine and mortality after coronary artery bypass grafting. AB - BACKGROUND: Changes in postoperative serum creatinine levels have been used to define acute renal injury in patients undergoing cardiac surgery with cardiopulmonary bypass. It remains unclear, however, whether subclinical increases in serum creatinine that do not meet current Acute Kidney Injury Network or RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria for acute renal injury are predictive of mortality after cardiac surgery. METHODS: Multivariate logistic regression was performed in a retrospective cohort of 3914 consecutive patients undergoing primary, isolated coronary artery bypass grafting with cardiopulmonary bypass to determine whether postoperative serum creatinine change independently predicts 30-day all-cause mortality in patients with normal renal function and with varying levels of preoperative renal insufficiency. To control further for selection bias, multivariate logistic regression was performed on a propensity-matched cohort (n = 2042) to determine whether subclinical increases in serum creatinine predict mortality. RESULTS: Negative change in serum creatinine was associated with reduced 30-day all-cause mortality. Even subclinical increases in serum creatinine were associated with increased mortality relative to patients with negative changes in serum creatinine (odds ratio, 3.93; 95% confidence interval, 1.68-9.22; P < .01). After propensity matching, subclinical increases in serum creatinine were still associated with increased mortality (odds ratio, 4.13; 95% confidence interval, 1.37-12.45; P = .01). CONCLUSIONS: Subclinical increases in serum creatinine that do not meet acute renal injury criteria are independently associated with 30-day all-cause mortality in patients with normal renal function or preoperative renal insufficiency undergoing coronary artery bypass grafting. PMID- 22054659 TI - Predictors and impact of postoperative atrial fibrillation on patients' outcomes: a report from the Randomized On Versus Off Bypass trial. AB - OBJECTIVE: The study objective was to determine the predictors of postoperative atrial fibrillation (POAF) in patients randomized to conventional coronary artery bypass graft (on-pump coronary artery bypass [ONCAB]) versus beating heart coronary surgery (off-pump coronary artery bypass [OPCAB]). METHODS: The subgroup of 2103 patients (of 2203 enrollees) in the Randomized On Versus Off Bypass trial with no POAF was studied (1056 patients in the ONCAB group and 1047 patients in the OPCAB group). Univariate and multivariate analyses were used to identify the predictors of POAF and the impact of POAF on outcomes. RESULTS: Use of ONCAB versus OPCAB was not associated with increased rates of POAF. Older age (P < .0001), white race (P < .001), and hypertension (P < .002) were predictors of POAF on multivariate analysis. In general, POAF led to a higher rates of reintubation (ONCAB: 6.3% vs 0.8% no POAF, P < .001; OPCAB: 7.4% vs 1.8% no POAF, P < .0001) and prolonged ventilatory support (ONCAB: 7.1% vs 2.3% no POAF, P = .001; OPCAB: 9.2% vs 3.4% no POAF, P = .0003). The rate of any early adverse outcome was higher in patients with POAF (all patients: 10% POAF vs 4.7% no POAF, P < .0001; ONCAB: 9% POAF vs 4.3% no POAF, P = .008; OPCAB: 11% POAF vs 5.1% no POAF, P = .001). The 1-year all cause mortality was higher with POAF for both groups (ONCAB: 5.4% POAF vs 2% no POAF, P = .009; OPCAB: 5.1% POAF vs 2.6% no POAF, P = .07). POAF was independently associated with early composite end point (odds ratio [OR], 2.23; confidence interval [CI], 1.55-3.22; P < .0001), need for new mechanical support (OR, 3.25; CI, 1.39-7.61; P = .007), prolonged ventilatory support (OR, 2.93; CI, 1.89-4.55; P < .0001), renal failure (OR, 5.42; CI, 1.94 15.15; P = .001), and mortality at 12 months (OR, 1.94; CI, 1.14-3.28; P = .01). CONCLUSIONS: In the Randomized On Versus Off Bypass trial, the strategy of revascularization did not affect the rate of POAF. Age, race, and hypertension were predictors of POAF. POAF was independently associated with a higher short term morbidity and higher 1-year mortality rates. PMID- 22054660 TI - Optimal surgical management of severe ischemic mitral regurgitation: to repair or to replace? AB - BACKGROUND: Ischemic mitral regurgitation, a complication of myocardial infarction and coronary artery disease more generally, is associated with a high mortality rate and is estimated to affect 2.8 million Americans. With 1-year mortality rates as high as 40%, recent practice guidelines of professional societies recommend repair or replacement, but there remains a lack of conclusive evidence supporting either intervention. The choice between therapeutic options is characterized by the trade-off between reduced operative morbidity and mortality with repair versus a better long-term correction of mitral insufficiency with replacement. The long-term benefits of repair versus replacement remain unknown, which has led to significant variation in surgical practice. METHODS AND RESULTS: This article describes the design of a prospective randomized clinical trial to evaluate the safety and effectiveness of mitral valve repair and replacement in patients with severe ischemic mitral regurgitation. This trial is being conducted as part of the Cardiothoracic Surgical Trials Network. This article addresses challenges in selecting a feasible primary end point, characterizing the target population (including the degree of mitral regurgitation) and analytical challenges in this high mortality disease. CONCLUSIONS: The article concludes by discussing the importance of information on functional status, survival, neurocognition, quality of life, and cardiac physiology in therapeutic decision making. PMID- 22054662 TI - Transcatheter aortic valve implantation versus surgical aortic valve replacement: a propensity score analysis in patients at high surgical risk. AB - OBJECTIVES: Transcatheter aortic valve implantation (TAVI) has recently been advocated to decrease perioperative risk in high-risk patients. In this propensity-score analysis we compared outcomes after TAVI to those after surgical aortic valve replacement (AVR). METHODS: From June 2009 through June 2010, 82 consecutive patients underwent TAVI via a transapical (n = 60) or transfemoral (n = 22) approach using the Edwards Sapien prosthesis (Edwards Lifesciences, Irvine, Calif). Mean patient age was 81.9 +/- 5.2 years, 64.6% were women. Logistic EuroSCORE was 23.6% +/- 1.4% and Society of Thoracic Surgeons score was 8.7% +/- 1.3%. A group of 82 patients after surgical AVR was retrieved from our database, yielding a control group that was matched to the cases with respect to baseline demographics and typical risk factors. RESULTS: Overall mortality did not differ significantly between TAVI and AVR groups at 30 days (7.3% vs 8.6%), 90 days (13.6% vs 11.1%), or 180 days (17.8% vs 16.9%; P = .889). Conversion to surgery was necessary in 2 (2.4%) TAVI cases. Perioperative stroke occurred in 2 (2.4%) cases per group. Pacemakers were implanted for new-onset heart block in 3.7% and 2.4% in the TAVI and AVR groups, respectively (P = 1.0). TAVI resulted in shorter operative times (P < .001), shorter ventilation times (P < .001), and shorter length of stay in the intensive care unit (P = .008). Duration of hospital stay, however, was not significantly different (P = .11). CONCLUSIONS: In our experience, mortality rates are similar after both types of procedure. Patients receiving TAVI benefit from faster postoperative recovery. Until more clinical data become available, the optimal procedure has to be determined for each patient according to individual risk factors. PMID- 22054664 TI - Influence of coagulating bath composition on the texture of fibres spun from blood plasma. AB - The effect of the composition of the coagulating bath on the formation of spun fibres from blood plasma protein has been investigated. The texture of these fibres is affected by the concentration of the coagulants, especially at low levels. The fibre retained an amount of sodium chloride, proportional to the salt level in the bath, which could be washed free from the fibre without redissolution. As a result a satisfactory level of ash in the textured product could be obtained. PMID- 22054663 TI - Identification of a disulfide bridge essential for structure and function of the voltage-gated Ca(2+) channel alpha(2)delta-1 auxiliary subunit. AB - Voltage-gated calcium (Ca(V)) channels are transmembrane proteins that form Ca(2+)-selective pores gated by depolarization and are essential regulators of the intracellular Ca(2+) concentration. By providing a pathway for rapid Ca(2+) influx, Ca(V) channels couple membrane depolarization to a wide array of cellular responses including neurotransmission, muscle contraction and gene expression. Ca(V) channels fall into two major classes, low voltage-activated (LVA) and high voltage-activated (HVA). The ion-conducting pathway of HVA channels is the alpha(1) subunit, which typically contains associated beta and alpha(2)delta ancillary subunits that regulate the properties of the channel. Although it is widely acknowledged that alpha(2)delta-1 is post-translationally cleaved into an extracellular alpha(2) polypeptide and a membrane-anchored delta protein that remain covalently linked by disulfide bonds, to date the contribution of different cysteine (Cys) residues to the formation of disulfide bridges between these proteins has not been investigated. In the present report, by predicting disulfide connectivity with bioinformatics, molecular modeling and protein biochemistry experiments we have identified two Cys residues involved in the formation of an intermolecular disulfide bond of critical importance for the structure and function of the alpha(2)delta-1 subunit. Site directed-mutagenesis of Cys404 (located in the von Willebrand factor-A region of alpha(2)) and Cys1047 (in the extracellular domain of delta) prevented the association of the alpha(2) and delta peptides upon proteolysis, suggesting that the mature protein is linked by a single intermolecular disulfide bridge. Furthermore, co-expression of mutant forms of alpha(2)delta-1 Cys404Ser and Cys1047Ser with recombinant neuronal N type (Ca(V)2.2alpha(1)/beta(3)) channels, showed decreased whole-cell patch-clamp currents indicating that the disulfide bond between these residues is required for alpha(2)delta-1 function. PMID- 22054665 TI - Some factors causing variation in the texture of similar muscles from comparable animals. AB - This paper reviews recent studies on pre- and postmortem changes in muscle tissue that cause variation in quality of similar muscles from animals of equal age, similar breeding and rearing, and processed under identical conditions. These studies indicate that the nervous state of the animal and struggling at death cause an undesirably high rate of glycolysis and breakdown of high-energy phosphates immediately before or after death in some animals. This results in a low pH at death or shortly after death and a rapid onset of rigor when the temperature of the carcass is still high. These conditions cause denaturation of sarcoplasmic and myofibrillar proteins and excessive shortening-and consequently toughness and loss of water-holding capacity. The extent of these changes varies widely between similar muscles from comparable animals which leads to concomitant variations in tenderness and juiciness of the meat. Another causal factor in this variation is the lack of activation of an intrinsic enzyme system which dissociates the Z-lines and improves tenderness. PMID- 22054666 TI - Reactivity of glycerol in intermediate moisture meats. AB - Non-enzymic browning (NEB) reactions between glycerol and some of the amino acids present in meat have been observed at 38 and 65 degrees C; l-lysine is the most reactive of the amino acids studied and l-cysteine and l-arginine the least. These NEB reactions also occur between glycerol and proteins (gelatin and casein). The reactions are not unique to glycerol as other polyhydric alcohols also form brown pigments with lysine. On prolonged air storage at 65 degrees C glycerol itself undergoes mild oxidation, ultimately yielding a brown solution. PMID- 22054667 TI - Evidence for differences in post mortem intramuscular phospholipase activity in several muscle types. AB - The neutral and polar lipids of chicken adductor longus and pork semitendinosus muscles have been analysed at several periods of post mortem ageing. A complete fatty acid analysis for pork muscle has also been carried out. The results revealed small changes in chicken leg muscle phosphatidyl ethanolamine and free fatty acid fractions, suggesting limited phospholipase A activity in this muscle. The pork muscle showed no changes. The results are considerably different from results obtained for chicken pectoralis major. The differences are discussed in the light of the structural and biochemical differences between the sarcotubular systems of red and white muscle fibres. PMID- 22054668 TI - Preservation of refrigerated meats with controlled atmospheres: Treatment and post-treatment effects of carbon dioxide on pork and beef. AB - Whole pork loins were divided into roasts and subjected to air control and carbon dioxide enriched atmospheres at 1 degrees C for up to 21 days. Quintuplicate samples of both control and carbon dioxide treated loins were transferred to air storage at 0,4,7, 14 and 21 days and further held for 0, 3(4), 7 and 10 days at 4 degrees C. Microbiological counts were taken at all time permutations. The results indicated a strong inhibiting effect of the carbon dioxide atmosphere on microbial growth as well as a marked residual effect during post-treatment storage in air. Satisfactory colour and odour were maintained on the loins for extended storage times, with visual and olfactory deterioration preceding microbial spoilage. Beef round wedges were treated in a similar manner. Although bacterial spoilage inhibition was comparable, colour degeneration was rapid and severe, making the method unsuitable for treatment of finished beef cuts. PMID- 22054669 TI - The effect of pre-rigor stretch and contraction on the post-rigor geometry of meat samples in relation to meat toughness. AB - The geometry of the muscle fibre and perimysial collagen components of meat subjected to pre-rigor stretch and contraction were examined. The changes in the configurations of these two components accompanying length changes in the muscle were used to explain the reported relationship between raw meat toughness and contraction state. The theory put forward proposes that in raw meat samples the muscle fibre component plays virtually no role in modifying the toughness of the meat sample with contraction state. This theory of the collagen component playing the major role is the same as that reported elsewhere. It is capable of explaining a reverse relationship between meat toughness and contraction state such as is found in cooked meat simply by invoking a firmer consistency for the muscle fibres which then act as fill between the collagen network fibres and hold them at an angle relative to the line of applied force. PMID- 22054670 TI - The prediction of beef carcass composition: A comparison of models. AB - Any attempt to summarise existing knowledge on the prediction of carcass composition without detailed dissection is bedevilled by the variety of methods used by different workers, not least in the analysis and presentation of their results. This paper examines one cause of the apparent confusion: the differences in interpretation arising from the use of different regression models in allowing for the effect of variable live weight or side weight. The part/whole relationships implied in examining the effect of a total weight on the weight of a part are considered, and by applying four regression models to two sets of published data, it is hoped to facilitate reconciliation of the conflicting results reported in the literature. PMID- 22054671 TI - The histology of blood splash in lamb. AB - Ecchymosis (blood splash), can occur in the carcasses of animals that have been stunned electrically or shot with a captive bolt. While blood splash presents no health hazard, it is likely to detract from the acceptable appearance of the meat. Based on light and electron microscopic studies, ecchymosis has been shown to be due to the localised discharge of blood from ruptured blood vessels into the surrounding muscle tissue. A small proportion of muscle fibres in a splashed region were distorted (~ 5 %) with irregular zones of high shortening interspersed with zones of lesser shortening. Such 'supercontracture' and its associated blood splash was markedly reduced by neuromuscular blocking agents. It is proposed that through supercontracture of some fibres, a severe strain is placed on adjacent blood vessels, occasionally leading to their rupture and hence to haemorrhaging. PMID- 22054672 TI - Evaluating physical activity: the AQAP questionnaire and its interpretation software. AB - OBJECTIVES: Updating Baecke physical activity questionnaire in French, validating this version named AQAP and developing software for a personalized interpretation of the results. METHOD: Validation conducted on 702 consultants in health prevention centers aged 18-79 years: reliability of the questionnaire when self administered, validity according to the energy expenditure per interview and reproducibility after two weeks (n=31). After two months, assessment of the questionnaire's impact on knowledge and behaviors in 320 young adults aged 18-29 years. RESULTS: The results from self- and interviewer-administered questionnaire were correlated (Kappa>0.60). Furthermore, the total physical activity index was correlated to the energy expenditure (rho=0.39, P<0.0001). The four physical activity indexes calculated from self-administrated questionnaires barely varied at the two-week interval (P >= 0.23, power >= 77%, accepted difference +/- 10%). Two months later, 80% of the participants had read the interpretation software report, 55% became conscious of their physical activity level, 43% increased their physical activity level and 42% reported being aware of the relationship between physical activity and health. CONCLUSION: AQAP characteristics are satisfactory and thus this questionnaire can be used on the general population in complement of an individual or collective action to promote physical activity and in epidemiological studies for analyzing the links between individual behaviors and health. PMID- 22054673 TI - Effect of curing salt and phosphate on the activity of porcine muscle proteases. AB - The effect of curing salt on the activity of porcine muscle proteases was evaluated, within the salt concentration range found in the manufacturing process of Spanish cured ham. Salt (NaCl) acts as a strong inhibitor of proteolytic activity; sodium nitrate and potassium nitrate do not affect cathepsin D activity; cathepsin L is inhibited at levels of the salts not found in cured ham, and Ca-dependent proteolytic activity is enhanced by nitrate concentrations below 800 ppm. The appearance of phosphate precipitates in several areas of ham has led to the study of phosphate effect on enzymatic activity. Results show that phosphate is an inhibitor of proteolytic activity. PMID- 22054674 TI - Effect of halothane genotype on muscle metabolism at slaughter and its relationship with meat quality: A within-litter comparison. AB - The effects of halothane genotype on muscle metabolism at slaughter and its relationship with meat quality were studied within 16 litters. Heterozygous boars and sows were mated and the offspring were halothane tested and bloodtyped to reveal the halothane (Hal) genotype of the 120 animals used (NN, Nn or nn). Following slaughter at 100kg live weight, muscle samples from M. longissimus dorsi (LD) and M. quadriceps (Qu) were taken immediately after exsanguination and analysed for glycogen, glucose-6-phosphate, lactate, creatine phosphate (CP), and adenosine triphosphate (ATP), as well as for enzyme activities representing both the oxidative and glycolytic pathways. The enzyme activities were similar for all genotypes. All muscle metabolites differed significantly between samples from NN and nn animals, with higher lactate and glucose-6-phosphate and lower glycogen, CP and ATP in the nn muscles. The heterozygote animals were intermediate or close to either of the homozygotes. Meat quality characteristics (drip loss, surface and internal reflectance and dielectric loss factor) were studied only in the LD muscle. Meat quality of the muscle from the heterozygote (Nn) animals was inferior to that from NN animals (no difference for internal reflectance) but better than that from nn animals. When reflectance and drip loss were combined into an index, very few values from the nn-animals were better than the total mean. Indexes from the dominant homozygotes were generally better than the mean and those of heterozygotes were approximately normally distributed around the mean. PMID- 22054675 TI - Carcass traits and meat quality of male lambs fed monensin or lasalocid. AB - Male lambs, crossbred Merino * Ille de France, were fed a diet supplemented with 31 mg monensin or 32 mg lasalocid per kg of feed dry matter from an initial body weight of 23.6-23.9 kg to the slaughter weight of approximately 40 kg. Carcass traits and meat quality were evaluated after slaughter; the values obtained were compared with those of the control group fed the same diet without the ionophore supplement. There were few significant differences among the individual groups in carcass value, sensoric and technological properties of meat and of its composition. However, the lasalocid-fed group seemed to be somewhat better in muscling and in the composition of meat. PMID- 22054676 TI - Amino acid composition of meat, fatty acid composition of fat and content of some chemical elements in the tissues of male lambs fed monensin or lasalocid. AB - Tissues of slaughtered male lambs fed for 56 days on a feed mixture, supplemented with either monensin or lasalocid, were analysed and compared with tissues of control lambs fed similarly but without ionophore supplement. The analyses carried out were for the amino acid composition of meat, fatty acid composition of intramuscular and perirenal fat, and for some chemical elements in meat, liver and kidneys. In meat of both supplemented groups of lambs a significant increase in tyrosine was observed. In the fat tissues of monensin-fed lambs a higher proportion of odd-carbon acid (heptadecanoic acid) was observed; differences in some other fatty acids among the groups were also found. Some significant differences in the chemical elements analysed were observed, particularly in liver, few in kidneys and none in the muscle of ionophore-fed groups. The quality of meat, as judged by the analyses for the substances mentioned, was little changed by supplementation of monensin or lasalocid in the feed of male lambs. PMID- 22054677 TI - Evaluation of lean meat quality in pigs using two electronic probes. AB - The Danish Fat-O-Meater grading probe (FOM) and the Fibre Optic Probe (FOP) developed at IFR, Bristol, were evaluated for their potential ability to predict lean meat quality in a sample of 76 pig carcasses showing a wide range of quality in the M. longissimus dorsi. When probings were made after chilling at about 20 h post mortem the correlations between probe value (FOP(u) and FOM(u)) and reflectance (EEL value), drip loss during storage and subjective assessment score for colour-structure were high (FOP(u) and reflectance, r = 0.89; drip loss, r = 0.78; subjective assessment, r = 0.90. FOM(u) and reflectance, r = 0.88; drip loss, r = 0.73; subjective assessment r = 0.81). Nevertheless, probe values could not be used to unambiguously group samples into normal, pale, soft, exudative (PSE) or dark, firm, dry (DFD) classes. Correlations between probe values at 45 min post mortem and measures of ultimate meat quality were much lower. Neither probe could potentially differentiate between normal and DFD meat at this time and differentiation between normal and PSE meat was also poorer. PMID- 22054678 TI - Evaluation of salt, polyphosphates and their blends at different levels on physicochemical properties of buffalo meat and patties. AB - The effects of sodium pyrophosphate (SPP), sodium tripolyphosphate (STPP), sodium hexametaphosphate (SHMP), sodium acid pyrophosphate (SAPP) and their blends at different levels (0.3, 0.5 and 0.7%), along with 2% sodium chloride on certain quality parameters of buffalo meat and patties were evaluated. The SPP, STPP and phosphate blends significantly increased pH, water-holding capacity (WHC), emulsifying capacity (EC), extractability of salt soluble proteins (SSP), colour of ground meat, decreased cooking loss (CL), improved emulsion stability (ES) and enhanced yield, texture and moisture retention of cooked patties. Compared to these phosphates, SAPP and SHMP had significantly poorer effects on improving the quality of meat and patties. The order of effectiveness of phosphates was SPP > STPP > SHMP. In general, pH, WHC, SSP, ES, yield and moisture content of patties increased progressively with increasing level of phosphate while CL decreased. Among blends containing two polyphosphates, those of 90% SPP + 10% SHMP and 75% SPP + 25% STPP were relatively more effective. A phosphate blend consisting of 65% SPP, 17.5% STPP and 17.5% SAPP was equally effective as that of SPP in improving the functionality of hot and chilled meat and had the advantage of reducing the amount of sodium by 3%. PMID- 22054679 TI - Evaluation of the contribution of skatole, indole, androstenone and androstenols to boar-taint in back fat of pigs by HPLC and capillary gas chromatography (CGC). AB - Fifteen samples of fat with boar taint were selected by means of a trained panel test, from 200 carcasses of entire male pigs, and they were analyzed to determine skatole, indole, 5alpha-Androst-16-en-3-one (5alpha-An), 5alpha-Androst-16-en 3alpha-ol (5alphaAn3alpha) and 5alpha-Androst-16-en-3beta-ol (5alphaAn3beta). The extraction was carried out with methanol, the extract was placed at -20 degrees C during 10 min to eliminate the fat and after evaporation of methanol a Florisil clean up was applied to obtain skatole and indole in a separate fraction from 5alphaAn and androstenols. Skatole and indole were determined by HPLC in normal phase with a Spherisorb-NH(2) column and 5alphaAn and androstenols were analyzed by capillary gas chromatography (CGC). Selective procedures were used for detection: ratio at 220 nm and 280 nm (skatole/indole) and CGC coupled to a mass spectrometer working in the SIM (selected ion monitoring) mode at m/z 272 (o5alphaAn) and m/z 274 (androstenols). The results obtained showed that skatole and 5alphaAn concentrations exceeded that typical thresholds values in more than 50% of samples analyzed, suggesting a similar influence on boar taint. 5alphaAn3beta showed higher concentrations than 5alphaAn3alpha, but lower than 5alphaAn, exceeding only 1.00 MUg/g in three samples. PMID- 22054680 TI - Technologie de la Viande et des Produits Carnes By J. P. Girard. INRA Publications, Versailles, 1988. 280 pp. Price: 275.00 F fr. PMID- 22054681 TI - First report and molecular characterization of Trypanosoma vivax in cattle from state of Pernambuco, Brazil. AB - This paper describes an outbreak of Trypanosoma vivax for the first time in the state of Pernambuco, Brazil, affecting dairy cattle in the municipality of Itambe in the northern coastal zone of the state. Clinical signs compatible with infection by blood protozoa and epidemic miscarriages were observed. The diagnosis of T. vivax was confirmed through biometric microscopy and molecular analysis with PCR and DNA sequencing. The T. vivax isolate detected in the present study proved to be genetically very close to other Brazilian isolates of the protozoan despite being geographically distant. PMID- 22054682 TI - Electrical stimulation and ultra-rapid chilling of pork. AB - Six pigs were stimulated at 5 min post mortem and six remained unstimulated. All the pigs were split hot and one side from each pig was rapidly chilled in two stages (air at -40 degrees C and 1 m/s for 80 min followed by 0 degrees C and 0.5 m/s for 130 min) and the other side was conventionally chilled (air at 0 degrees C and 1 m/s for 24 h). The weight loss from rapidly chilled sides was approximately 1% less than that from conventionally chilled controls. Cooked samples of Longissimus dorsi were tougher from unstimulated rapidly chilled sides (0.23 J) than from unstimulated conventionally chilled sides (0.18 J), whilst samples from both stimulated treatments were significantly more tender (0.15 J). These differences in toughness are thought to be due to a combination of cold shortening and lack of conditioning. The average pH in the longissimus dorsi of both rapidly and conventionally chilled stimulated sides at 50 min post mortem was 5.57 and samples from these muscles were slightly paler and more watery than the unstimulated controls. PMID- 22054683 TI - Predicting cutability of pork carcasses and hams using the Hennessy and Chong Fat Depth Indicator. AB - Hot and cold Fat Depth Indicator (FDI) readings were taken on seventy-four pork sides to examine the relative precision of different measurement locations. Fat measurements taken over the M. longissimus opposite the fourteenth thoracic vertebra (CD = 47.5; RSD = 1.63) and the last lumbar vertebra (CD = 61.1; RSD = 1.40) were the measurement locations most closely associated with percentages of four trimmed lean cuts. Using certain combinations of carcass weight and/or hot and cold FDI readings in multiple regression equations, 71.0% (RSD = 1.35) and 63.3% (RSD = 1.55), respectively, of the variability in percentage yields of four lean cuts could be explained; this was as much as 40 percentage points more than that explained by average backfat thickness (first rib, last rib, last lumbar vertebra) taken on the split surface in the dorsal midline. When added to an unpublished equation, the addition of up to four hot or cold FDI readings made dramatic increases in the explained variation in carcass yields of four lean cuts. In each of two studies involving green, skinned hams, FDI readings explained a low percentage of the variability in percentage of boneless, defatted, deseamed lean. However, it was determined that these low relationships were primarily due to the site selections at which the hams were probed-not because of an inadequacy of the FDI to measure fatness. A third study, involving different FDI probe sites, taken on intact sides along the ham to loin-belly juncture, determined that the best of these FDI readings could account for a maximum of 66.1% of the variability (RSD = 2.75) in yield of bone-in, skinned, defatted hams; a four-variable prediction equation developed using two FDI readings, untrimmed ham weight and muscling score explained 83.9% of the variation (RSD = 2.04). PMID- 22054684 TI - Breakdown of connectin during cooking of meat. AB - Light-scattering studies on extracts of meat have confirmed the heat-induced breakdown of connectin previously observed by SDS gel electrophoresis. Because of the high subunit MW (~10(6)) of connectin, the weight-average molecular weight of whole muscle undergoes a relatively large decrease when connectin is broken down during heating of meat. In cold-shortened muscle, breakdown of connectin by proteolysis was as rapid as in control samples, suggesting that connectin exists in an exposed environment rather than as a core to thick filaments. The breakdown of connectin during heating at 60 or 80 degrees C for 40 min was more extensive than during ageing for 3 weeks at 2 degrees C. Hence, the partial proteolysis of connectin during storage at 2 degrees C is unlikely to be responsible for tenderisation induced by ageing. PMID- 22054685 TI - Electrical stunning and stillness of lambs. AB - The stillness obtained with head-to-back stunning results from the current depolarizing spinal neurones. The same effect can be achieved by sequentially applying a head stun, followed by a current through the heart to stop it and a current down the spinal cord to abolish movement. The level of speckle bruising for this sequential stun is lower than that associated with head-to-back stunning and is similar to that of head-to-foreleg stunning. After head-only stunning, current passed continuously down the spinal cord through a good contact at voltages around 40 V gave adequate stillness, which improved when the voltage was raised to 80 V. With a frequency of 14 Hz, 40 V presented no hazard to workers. After head-only stunning, a brief application of current down the entire spinal cord for 2-4 s at 110 V or greater also effectively suppressed movement. With legs as contact points voltages as high as 400 V were necessary. For effective animal stillness good electrode contact is necessary and electrodes should be placed as close to the spinal cord as possible. With a continuous current flowing the oesophagus remained closed until muscle exhaustion occurred; even with a brief current down the spinal cord, the oesophagus remained closed for at least 30 s. Low voltage stimulation in the form of a continuous current cannot replace high voltage stimulation, but can supplement it, and therefore could be incorporated into the electrical stimulation process. Head-only stunning, followed by a cut through the major blood vessels of the neck, is acceptable for Halal slaughter and is now in use commercially in New Zealand. Subsequent movement is suppressed by a spinal discharge at 400 V using leg contacts. PMID- 22054686 TI - Species identification of cooked meats by enzyme-staining of isoelectricfocusing gels. AB - By extracting cooked meat products with 6 m guanidine hydrochloride and then dialysing the extract into 1 % Triton X-100, the activity of adenylate kinase (AK) and creatine kinase (CK) may be at least partly recovered, provided the meat was not heated above ~120 degrees C (AK) or ~105 degrees C (CK). A wide range of animal species may be identified in cooked meats by staining isoelectricfocusing gels for these two enzymes. However, if a sample consists of mixed flesh from different species, hybrid creatine kinase dimers form during dialysis and the additional bands complicate interpretation of gel patterns. PMID- 22054687 TI - The shelf life of chilled sheep livers packed in closed tubs. AB - Livers incubated at 30 degrees C in closed tubs developed floras dominated by Enterobacteriaceae. At chiller temperatures, floras were ultimately dominated by psychrotrophic lactobacilli. Tub-packed livers can have an extended shelf life similar to that reported for vacuum-packed liver. PMID- 22054688 TI - Comparison of bacterial contamination of blood conservation system and stopcock system arterial sampling lines used in critically ill patients. AB - BACKGROUND: Commonly placed to monitor blood pressure and to aspirate blood, arterial lines frequently cause complications. The blood conservation system (BCS) forms a closed infusion line and may be expected to reduce complications caused by intraluminal contamination. We compared microbial contamination resulting from use of BCS and 3-way stopcock catheterization. METHODS: Patients who required arterial catheterization for at least 24 hours in our intensive care unit were randomly assigned to receive an arterial pressure monitoring system either with the BCS (test group) or with a 3-way stopcock (comparator group). To evaluate arterial line contamination, we qualitatively assessed the contamination of the catheter tip and intraluminal fluid. RESULTS: We analyzed microbial contamination for a total of 216 arterial catheters: 109 in the test group and 107 in the comparator group. We found no difference in the incidence of catheter tip colonization in the 2 groups (test group, 8/109 vs comparator group, 11/107; P = .48). There was a statistically significant correlation between catheter tip colonization and duration of arterial line utilization. We found statistically significantly lower intraluminal fluid contamination in the test group (test group, 2/109 vs comparator group, 9/107; P = .03). There was no relationship between intraluminal fluid contamination and catheter tip contamination. CONCLUSION: There was less microbial contamination of intraluminal fluid when BCS was used for arterial catheterization. PMID- 22054689 TI - Effectiveness of a multidimensional approach to reduce ventilator-associated pneumonia in pediatric intensive care units of 5 developing countries: International Nosocomial Infection Control Consortium findings. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common health care-associated infections in pediatric intensive care units (PICUs). Practice bundles have been shown to reduce VAP rates in PICUs in developed countries; however, the impact of a multidimensional approach, including a bundle, has not been analyzed in PICUs from developing countries. METHODS: This was a before-after study to determine rates of VAP during a period of active surveillance without the implementation of the multidimensional infection control program (phase 1) to be compared with rates of VAP after implementing such a program, which included the following: bundle of infection control interventions, education, outcome surveillance, process surveillance, feedback on VAP rates, and performance feedback on infection control practices (phase 2). This study was conducted by infection control professionals applying the National Health Safety Network's definitions of health care-associated infections and the International Nosocomial Infection Control Consortium's surveillance methodology. RESULTS: During the baseline period, we recorded a total of 5,212 mechanical ventilator (MV)-days, and during implementation of the intervention bundle, we recorded 9,894 MV-days. The VAP rate was 11.7 per 1,000 MV-days during the baseline period and 8.1 per 1,000 MV-days during the intervention period (relative risk, 0.69; 95% confidence interval, 0.5-0.96; P = .02), demonstrating a 31% reduction in VAP rate. CONCLUSIONS: Our results show that implementation of the International Nosocomial Infection Control Consortium's multidimensional program was associated with a significant reduction in VAP rate in PICUs of developing countries. PMID- 22054690 TI - Spray-chilling and carcass decontamination systems using lactic and acetic acid. AB - After slaughter, beef carcasses (n = 20) in groups of two were subjected to five treatments (one side only) including intermittent spray-chilling using water, 1% acetic acid or 1% lactic acid, or a single spray treatment with 1% acetic acid or 1% lactic acid. Intermittent spray-chilling consisted of two sprays of 30 s duration per hour for 12h. Single spray treatment consisted of one 30 s spray after entering the chill cooler. The other side of each carcass (control) was air chilled (at 2 to 3 degrees C; air velocity 1 to 3 m/s) only. Five subprimal cuts were taken from each side at 48 h post mortem, vacuum packaged and stored for 28 days at 2 degrees C. Intermittent sprays of sides with acetic or lactic acid resulted in significant (1.8-4.3 log/cm(2)) reductions in aerobic plate count of the strip loin, boneless rib and clod over their controls after these subprimal cuts had been vacuum packaged and stored for 28 days at 2 degrees C in high oxygen barrier (HOB) film. Lactobacillus spp. were dominant in the microflora of the subprimals from the control and treated sides. When sides were treated with a single sprays of acid, significant reductions in APC were noted only for some cuts of sides treated with lactic acid. After 28 days of storage, there were few significant differences in percentage purge, lean color, and off-odor scores between subprimals from control and treated sides. PMID- 22054691 TI - Differentiation of meat from horse, donkey and their hybrids (mule/hinny) by electrophoretic separation of albumin. AB - Meat from the species horse, donkey and their hybrids, mule/hinny, can be reliably identified by determination of genetic variants of serum albumin by starch gel electrophoresis of meat extracts. Staining of the starch gel for carboxylesterase activity permits differentiation of most horses from donkeys while mules/hinnies cannot be distinguished from horses by their esterase activity alone. PMID- 22054692 TI - Fracture toughness of frozen meat. AB - The fracture toughness and dynamic mechanical moduli of frozen beef M. semitendinosus were investigated at various sub-zero temperatures using several different test geometries. Traditional fracture mechanics methods were considered inapplicable to frozen meat, since considerable plastic flow occurs in addition to elastic deformation and fracture. Graphical work area methods still apply, based on calculating areas under load-deflection diagrams to measure the energy used up to fracture. Total work to fracture was found to vary both with temperature and geometry, with a peak occurring between -10 degrees C and -15 degrees C. It was shown that it is possible to separate out the components of fracture and flow using two methods: microtome cutting and compact tension. In microtome cutting, the cutting energy was found to depend on the thickness of cut, increasing linearly from 50 MUm to 500 MUm. This variation is attributed to a dependence of the volume of the plastic zone size at the cutting tip on the thickness. By extrapolation to zero thickness, an essential value of fracture energy of approximately 100J/m(2) was determined, assuming the absence of large scale plastic yielding. It was also possible to determine a value for the essential work of fracture using graphical work area methods in compact tension, obtaining values between 100 and 200 J/m(2). Dynamic mechanical testing showed loss peaks in mechanical damping occurring between -5 degrees C and -10 degrees C, with both temperature and magnitude of these peaks varying with frequency. Cryo-scanning electronic microscopy showed evidence of the nature of the fracture transition within frozen meat, indicating ductile deformation at higher temperatures (above -15 degrees C), and brittle fracture at lower temperatures (below -15 degrees C). PMID- 22054693 TI - Effects of oestradiol-17beta implantation on performance, carcass traits, meat sensory traits and endocrine aspects of bulls and steers. AB - Twenty-eight Simmental bull calves were randomly allotted to one of three treatments at birth. Ten bulls (IB) and nine steers (IS), castrated within 3 days of birth, were implanted with oestradiol (E(2)). The remaining calves were non implanted, control bulls (CB). Calves were implanted within 3 days of birth and at 200-day intervals until slaughter at 14.8 months of age and at a mean carcass weight of 381.6 kg. Blood samples were taken every 14 days from 9.8 through 14.8 months and serum was analyzed for E(2) and testosterone (T) levels. Carcasses were chilled in a 3 to 7 degrees C cooler. Carcass data were obtained and aged longissimus dorsi steaks were evaluated by a trained sensory panel and a Warner Bratzler shear (WBS) device. Scrotal circumferences were smaller (P < 0.0.5) for IB than for CB. Control bulls had heavier weaning weights (P < 0.05) than IB and higher (P < 0.05) feedlot gains than IS. Implanted steers required more (P < 0.05) feed/unit of gain than CB and IB. Implanting bulls with E(2) increased (P < 0.05) serum E(2) levels and tended (P < 0.10) to reduce T levels. Serum E(2) in IS and IB were drastically increased (P < 0.05) for 4 to 6 weeks following re implantation during the feedlot phase, then sharply declined. Implanted steer carcasses had more youthful maturity scores than CB carcasses. The incidence of hear ring (dark, coarse, band formation) was greater (P < 0.05) for IB than for IS, probably because of the thinner fat cover (P < 0.05) on IB. Ribeye areas were smaller (P < 0.05) and yield grades were higher for IS than for CB. Testicle weights were not significantly different between IB and CB, although variability was greater for IB. Carcass masculinity was least (P < 0.05) for IS, and IB were less (P < 0.05) masculine than CB. The only difference in longissimus dorsi sensory traits was that steaks from IB were juicier than steaks from CB. Also, WBS values were lower (P < 0.05) for IS than for CB. PMID- 22054694 TI - Effects of cryogenic chilling on beef carcass grade, shrinkage and palatability characteristics. AB - Alternate right or left sides of 90 carcasses were randomly selected and chilled at -70 degrees C for 5 h, held at +16 degrees C for 4 h and held at 1 degrees C for 15 h (rapid chill-RC). The remaining sides were chilled at -7 degrees C for 24 h (conventional chill-CC). Physical measurements and USDA quality grade data were obtained at 24 h post mortem and palatability samples were collected at 3-5 days post mortem. RC sides had 0.9% less shrinkage (P < 0.05) at 24 h post mortem when compared to paired CC sides. Beef sides that were given the RC treatment had a darker, softer lean (P < 0.01) and received higher marbling scores (P < 0.01) at 24 h post mortem than did CC sides. Loin steaks from RC sides had longer sarcomeres, less shear resistance and higher sensory panel tenderness ratings. It may be possible to rapidly chill carcasses with less carcass shrinkage and with no detrimental effects on USDA quality grade or on beef palatability. PMID- 22054695 TI - Observations on muscle press juice from bovine, ovine and porcine muscles. AB - Differences in the amounts and protein concentrations of muscle press juices from fresh and frozen psoas and l. dorsi muscles of bovine, ovine and porcine origin suggest the value of species and anatomical selection for functional applications in meat products. PMID- 22054697 TI - The impact of organochlorines cycling in the cryosphere on global distributions and fate--2. Land ice and temporary snow cover. AB - Global fate and transport of gamma-HCH and DDT was studied using a global multicompartment chemistry-transport model, MPI-MCTM, with and without inclusion of land ice (in Antarctica and Greenland) or snow cover (dynamic). MPI-MCTM is based on coupled ocean and atmosphere general circulation models. After a decade of simulation 4.2% gamma-HCH and 2.3% DDT are stored in land ice and snow. Neglection of land ice and snow in modelling would underestimate the total environmental residence time, tau(ov), of gamma-HCH and overestimate tau(ov) for DDT, both on the order of 1% and depending on actual compartmental distribution. Volatilisation of DDT from boreal, seasonally snow covered land is enhanced throughout the year, while volatilisation of gamma-HCH is only enhanced during the snow-free season. Including land ice and snow cover in modelling matters in particular for the Arctic, where higher burdens are predicted to be stored. PMID- 22054698 TI - The new UN CRC General Comment 13: "The right of the child to freedom from all forms of violence"--changing how the world conceptualizes child protection. AB - The UN Committee on the Rights of the Child established CRC General Comment 13 (April 2011) to address today's unabating high rates of violence against children globally despite CRC advances. GC13 provides clear interpretations and stronger detail to supplement the legal language of CRC Article 19, intended to establish protection of children from all forms of violence. Through GC13, the Committee seeks to strengthen policy and practice implementation for all children, including every nation's most vulnerable, by clearly establishing measurable indicators: structure, process and outcomes to children-through improved technical information, expertise and assistance. Based on knowledge and experience gained over the 22 years since the CRC was adopted, GC13 advances best practice approaches and technical resources for States Parties and professionals on preventing violence against children, and on strengthening protection programs, systems, services, research, monitoring, evaluation and reporting. This article addresses child rights and protection issues which have been raised during this period, as well as during the consultation and resulting dialogues, such as the rights of children in early/forced marriage, and the role of the State Party as responsible caregiver when parents or families are not capable of providing protection. PMID- 22054699 TI - Changing radiation dose from diagnostic computed tomography examinations in Saskatchewan. AB - PURPOSE: Follow-up study to observe if provincial mean effective radiation dose for head, chest, and abdomen-pelvis (AP) computed tomographies (CTs) remained stable or changed since the initial 2006 survey. METHODS: Data were collected in July 2008 from Saskatchewan's 13 diagnostic CT scanners of 3358 CT examinations. These data included the number of scan phases and projected dose length product (DLP). Technologists compared projected DLP with 2006 reference data before scanning. Projected DLP was converted to effective dose (ED) for each head, chest, and AP CT. The total dose that the patients received with scans of multiple body parts at the same visit also was determined. RESULTS: The mean (+/- SD) provincial ED was 3.4 +/- 1.6 mSv for 1023 head scans (2.7 +/- 1.6 mSv in 2006), 9.6 +/- 4.8 mSv for 588 chest scans (11.3 +/- 8.9 mSv in 2006), and 16.1 +/- 9.9 mSv for 983 AP scans (15.5 +/- 10.0 mSv in 2006). Single-phase multidetector row CT ED decreased by 31% for chest scans (9.5 +/- 3.9 mSv vs 13.7 +/- 9.7 mSv in 2006) and 17% for AP scans (13.9 +/- 6.0 mSv vs 16.8 +/- 10.6 mSv in 2006) and increased by 19% for head scans (3.2 +/- 1.2 mSv vs 2.7 +/- 1.5 mSv in 2006). The total patient dose was highest (33.8 +/- 10.1 mSv) for the 20 patients who received head, neck, chest, and AP scans during a single visit. Because of increased utilisation and the increased CT head dose, Saskatchewan per capital radiation dose from CT increased by 21% between 2006 and 2008 (1.14 vs 1.38 mSv/person per year). CONCLUSION: Significant dose and variation reduction was seen for single-phase CT chest and AP examinations between 2006 and 2008, whereas CT head dose increased over the same interval. These changes, combined with increased utilisation, resulted in per capita increase in radiation dose from CT between the 2 studies. PMID- 22054700 TI - Pictorial essay: pitfalls in magnetic resonance imaging of the shoulder. AB - Numerous imaging pitfalls of normal variants due to imaging technique and artifacts can be seen on routine magnetic resonance imaging of the shoulder. Familiarity with these pitfalls is crucial to avoiding diagnostic errors. Understanding of the common causes of shoulder imaging artifacts will enable the radiologist to make rational changes in imaging technique to eliminate or reduce the effects of artifacts on magnetic resonance images. This pictorial essay highlights possible pitfalls that arise from imaging techniques, imaging artifacts, and normal variations, and how they may be recognized. PMID- 22054701 TI - A 5-year prospective study of predictors for disability pension among patients with major depressive disorder. AB - OBJECTIVE: There is a scarcity of prospective long-term studies on work disability caused by depression. We investigated predictors for disability pension among psychiatric patients with MDD. METHOD: The Vantaa Depression Study followed up prospectively 269 psychiatric in- and out-patients with DSM-IV MDD for 5 years with a life chart, including 230 (91.3%) patients belonging to labour force. Information on disability pensions was obtained from interviews, patient records and registers. RESULTS: Within 5 years, 20% of the patients belonging to labour force at baseline were granted a disability pension. In multivariate analyses, the significant baseline predictors for granted disability pension were age >=50 years (HR = 3.91, P < 0.001), subjective inability to work (HR = 2.14, P = 0.008) and introversion (HR = 1.08, P = 0.049). When follow-up variables were included, the predictors were age more than 50 (OR = 6.25, P < 0.001), proportion of time spent depressed (OR = 14.6, P < 0.001), number of comorbid somatic disorders (OR = 1.47, P = 0.013) and lack of vocational education (OR = 2.38, P = 0.032). CONCLUSION: Of psychiatric patients with depression, one-fifth were granted a disability pension within 5 years. Future disability pension can be predicted by baseline older age, personality factors, functional disability, lack of vocational education and comorbid somatic disorders. Longitudinally, accumulation of time spent depressed appears decisive for pensioning. PMID- 22054702 TI - Effects of breed and nutrition on the productive traits of beef cattle in South East Brazil: Part 2-Tissue distribution and carcase composition. AB - This paper is the second in a series recording the effects of breed and nutrition on the productive traits of Nelore, Guzera, Charolais and Canchim cattle in south east Brazil. Significant treatment variations were recorded in carcase bone weights but differences in meat to bone ratios were not sufficiently marked to demonstrate that bone might grow at the expense of muscle when animals are maintained on particularly severe nutritional regimes. A simple carcase weight to length ratio was shown to be highly correlated with total bone proportion but not with yield of saleable meat. Recovery of total saleable meat was only marginally and not significantly affected by breed but was significantly affected by treatment. The increased levels of fatness in the carcases of the zebu and, in particular, all animals finished in feedlot, that affected the yield of saleable meat, was also thought to be responsible for the decreased recovery of first quality meat in these carcases. In general, tissue differences were more noticeable between treatments than between breeds and reflected the varying nutritional status of the animals pre-slaughter. PMID- 22054703 TI - Electrical stunning of veal calves. AB - A total of sixty-two calves with body weights of 200 kg and with preimplanted ECoG electrodes on the dura mater, were electrically stunned using various currents, voltages and stunning equipment. To stun 90% of the calves effectively, a current strength of 0.87 A is estimated to be necessary when using scissor model tongs. Effective stunning means immediate (within 1 s) induction of unconsciousness by a general electroplectic insult. Atrial fibrillation is a frequently occurring phenomenon after electrical stunning when the electrodes are placed between the eye and the ear. The relatively short duration of the insult in calves compared with pigs, as well as the clonic spasms occurring 10s after stunning, are major drawbacks to the practical application of electrical stunning of veal calves. The experiments show that these drawbacks can be eliminated by modifying the form and position of the electrodes. PMID- 22054704 TI - Influence of pH on the Warner-Bratzler shear properties of mutton. AB - Initial yield and peak shear force values obtained for stretched muscles cooked at 80 degrees C for different times decreased linearly at a similar rate with increasing pH, which is consistent with the prime effect of pH being on the myofibrillar structure. The tenderising effect of pressure-heat treatment on stretched and cold-shortened muscle decreased rapidly with increase in ultimate pH until, at values near 7, the effect disappeared. Increased ultimate pH effectively eliminated the large increase in shear force values, occurring in cold-shortened muscle of normal pH and attributable to heat denaturation of myosin, as cooking temperature was increased above 60 degrees C. PMID- 22054705 TI - The relationship between conformation and the yield and distribution of lean meat in the carcasses of British pigs, cattle and sheep: A review. AB - Information available on the value of conformation as a predictor of carcass composition in the British livestock population is reviewed, particular reference being made to recent Meat and Livestock Commission (MLC) trials using the visual conformation assessments employed in national carcass classification schemes. In mixed breed populations, the visual conformation assessments are positively related to lean to bone ratio and muscle thickness, although the correlations are generally low. Their relationship with carcass lean content depends on the effectiveness with which variation in fatness is eliminated since fatter carcasses tend to be given higher conformation scores. Conformation provides little information about the proportion of total lean occurring in the higher priced joints. The value of conformation in a mixed breed population depends to an important extent on its ability to identify breed differences in carcass characteristics. Although of some value in this respect, it is less effective than actual breed identification. Within-breed regressions on conformation are generally in the same direction as those in the mixed breed populations, although the precision of prediction is lower. The results indicate that conformation has little practical value as a predictor of carcass composition within breed. PMID- 22054706 TI - Muscle: Bone ratios in beef rib sections. AB - Thirty-eight steers and thirty heifers (14 to 17 months of age, from F(1) Hereford * Brahman cows bred to Angus or Hereford bulls), were either forage-fed for 123 days on millet-bermudagrass pasture or grain-fed for 90 days on a high concentrate diet and were then commercially slaughtered. Warm carcass weights ranged from 167.8 kg to 324.3 kg. At 24 h post mortem, Texas Agricultural Experiment Station personnel (1) assigned scores or took measurements on each carcass for all factors used in yield grading and quality grading, (2) measured the length of hind leg (HL) and carcass length (CL) and (3) assigned a score for carcass muscling (MS) and, as appropriate, made an adjusted longissimus muscle area (ALA) evaluation. The 9th-10th-11th rib section from one side of each carcass was physically separated into longissimus muscle, fat, 'other soft tissue' and bone and ether extract determinations of the longissimus muscle and 'other soft tissue' components were made and used to adjust the yields of each of these components to a fat-free basis. Muscle to bone ratios ranged from 2.38 to 4.37. With both age and carcass weight held constant, diet, breed and sex explained only 35.8% of the variation in muscle to bone ratio. The best simple correlation with muscle to bone ratio was ALA/CL (r = .59). Other measures significantly correlated with muscle to bone ratio included ALA (r = 0.55), MS (r = 0.50) and carcass weight (r = 0.49). Multiple regression analyses identified a three-variable subset comprised of ALA, carcass weight and CL which was related (P < 0.01) to muscle to bone ratio R(2) = 0.41). Data suggest that muscle to bone ratios differ widely among beef carcasses of similar genetic-management history and that there are carcass measures useful for predicting muscle to bone ratio. PMID- 22054707 TI - Enhancement of lean characteristics of veal carcasses by electrical stimulation. AB - Forty Holstein vealers (approximately 16 weeks of age) were slaughtered, skinned, split longitudinally and one side was electrically stimulated (700 V, 2 A and seventeen impulses) for 1 min. Internal temperatures of the rib and round were recorded at 1 h and 24 h post mortem. Approximately 24 h post mortem, lean colour scores were assigned to the cross-section of the longissimus muscle at the 11th 12th rib interface, to the outside surface of the biceps femoris muscle and to the rectus abdominis and transverse abdominis muscles of the flank; lean texture and firmness scores were also assigned to the cut surface of the longissimus muscle. 'House grades' were assigned to each side of each carcass by plant personnel. Initial (1 h) rib and round temperatures were significantly higher for the electrically stimulated sides; however, at 24 h, neither round nor rib temperatures differed between control and electrically stimulated sides. Lean colour, firmness and texture scores for longissimus muscles were significantly (P < 0.0001) improved by electrical stimulation. Electrically stimulated sides also had lighter lean colour scores in the rectus and transverse abdominis and biceps femoris muscles. Electrical stimulation increased the number of carcasses receiving the top 'house grade' and reduced the number of carcasses in the lowest 'house grade'. These data indicate that electrical stimulation will improve lean colour, firmness and texture of veal carcasses when ribbed and evaluated after a 24 h chill. PMID- 22054708 TI - Mechanisms of ultrastructural changes in electrically stimulated beef Longissimus muscle. AB - Three steers, ranging in grade from USDA low to average Good, were used in the evaluation of the effect of electrical stimulation (ES) on structural properties of the beef longissimus muscle. The left sides were electrically stimulated with 1-A current (delivering 145-250 V through the sides) for 2 min by applying eight bursts of 15-s duration. The right sides were not stimulated (controls). Samples of the longissimus muscle were removed at the sixth lumbar area 48 h post mortem and processed for light and transmission electron microscopy. Light and electron micrographs of stimulated muscle revealed irregular (contraction) bands, superstretching of myofibrils, absent or ill-defined I-, A- or Z-lines, tearing of myofibrils, the presence of empty vesicles and fragmentations of myofibrils at the Z-lines. Therefore, some of the mechanisms of tenderisation of electrically stimulated muscle would appear to result from physical disruption of myofibrils and possibly autolytic proteolysis. PMID- 22054709 TI - Revascularization of the ischemic hand with arterialization of the venous system. AB - Chronic ischemia in the upper extremity is a challenging condition for both patients and surgeons. When ischemia reaches a critical level, tissue loss ensues, which results in necrosis of fingers at various levels. Amputation of necrotic digits, without addressing the etiology of the necrosis, often results in wound-healing problems and more proximal amputations. The purpose of this report was to describe a surgical technique that improves vascular supply to the hand and allows for healing of the amputation sites and relief of pain through arterialization of the venous system. PMID- 22054713 TI - Instructions to Contributors. PMID- 22054710 TI - Synchronous bilateral breast cancer in a patient with kindler syndrome. PMID- 22054714 TI - Operative Dentistry Home Page. PMID- 22054715 TI - [Evaluation of the impact of prescription analgesic during the anaesthesia consultation on the incidence of postoperative pain at home in ambulatory orthopaedic surgery]. AB - INTRODUCTION: Postoperative pain at home in ambulatory surgery is a major problem. To improve its management, the French society of anaesthesia emphasizes the importance of writing prescriptions for analgesic during the preanaesthetic consultation. The objective of this study was to assess the impact of this prescription on the incidence of postoperative pain at home in ambulatory orthopaedic surgery. PATIENT AND METHODS: We conducted a prospective evaluation in the ambulatory surgery unit of Rouen University Hospital. We were able to identify two periods of 1 year with implementation of a systematic prescription of analgesics during the postoperative period (P1) or during the preanaesthetic consultation (P2). The evaluation of this measurement was made by a telephone survey conducted the day after surgery. The main parameter was the incidence of postoperative pain at home defined by the occurrence of a pain greater to 3/10 on a numerical scale (FR). Secondary parameters were demographic and anaesthetic data, the incidence of moderate pain (FR <= 3), treatment adherence and patient satisfaction. RESULTS: We included 638 patients and 531 were analysed: 28% of patients had an EN greater than 3 the day following surgery. There is no difference between the two periods (30% for P1 versus 27% for P2). The analysis of subgroups showed that in the general anaesthesia group, 30% of patients had an EN greater than 3 for P1 versus 18% for P2 (P<0.01). Furthermore, 55% of patients expressed moderate pain (FR <= 3) for P1 versus 22% for P2 (P<0.01). Moreover, 89% of patients reported having an adequate analgesic treatment. The overall observance was 64%, 53% for P1 versus 75% for P2 (P<0.01). DISCUSSION: The systematic prescription of analgesics during the preanaesthetic consultation does not decrease the intensity of moderate to severe pain. On the other hand, this procedure seems to be positive for the people who underwent a general anaesthesia. PMID- 22054716 TI - [From iatrogenesis to medical errors: review of the literature and analytical approach]. AB - Iatrogenesis and medical errors have been increasingly studied over the past years. Because of the lack of consensus concerning the definitions, it remains difficult to draw general conclusions from the published. Moreover, it is still likely to be underestimated because of underreporting. This review aims at evaluating the overall incidence of iatrogenesis and medical errors in anaesthesia and intensive care and at discussing the strategies to prevent these incidents, at the individual or systemic level. PMID- 22054717 TI - Networks in Caenorhabditis elegans. AB - The network paradigm has become a pervasive theme in biology over the last decade, as increasingly large functional genomic datasets are being collected to interrogate regulatory influences, physical interactions, and genetic dependencies between genes, transcripts, and proteins. These 'molecular interaction' networks can be analyzed collectively and individually to define their global architecture and local patterns of connectivity. These structural features ultimately underlie functional properties such as robustness, modularity, component circuitry (e.g. feedback loops), dynamics, and responses to perturbations. This review focuses on recent progress in elucidating molecular interaction networks using different kinds of functional assays in the classical genetic model for animal development, the roundworm Caenorhabditis elegans, with representative examples to illustrate current directions in different areas of network biology. PMID- 22054718 TI - Cardiac rehabilitation in skilled nursing facilities: a missed opportunity. AB - BACKGROUND: After hospitalization for a cardiac event, older adults are frequently discharged to a skilled nursing facility (SNF) for postacute care. The American Association of Cardiopulmonary Rehabilitation recommends that cardiac care be integrated into procedures at SNFs. OBJECTIVE: We undertook this research to describe the characteristics of patients in SNFs after a cardiac event and the cardiac care delivered at SNFs. METHODS: A dual approach included (1) a retrospective medical record review of consecutive patients admitted to 2 hospital-based SNFs after a cardiac event (n = 80), and (2) surveys from healthcare professionals (n = 21) working in these facilities. RESULTS: Thirty two percent of patients were not candidates for cardiac rehabilitative interventions because they had been rehospitalized, discharged to long-term care facilities, or manifested contraindications to exercise. No standard assessment of exercise tolerance was evident, and although 70% of patients were discharged home, cardiac-specific discharge education was seldom evident. Healthcare professionals in SNFs reported that standard procedures for cardiac care services were lacking. CONCLUSION: The integration of cardiac care into SNFs is important to ensure the safety of therapy and improve the transition of patients from SNFs to outpatient cardiac rehabilitation programs. PMID- 22054719 TI - Symptoms and functional performance in Korean immigrants with asthma or chronic obstructive pulmonary disease. AB - OBJECTIVES: People with chronic obstructive lung diseases often experience a variety of symptoms. Few studies, however, have described these symptoms in detail. This study sought to examine concurrent symptoms, symptom clusters, and the effects of symptoms on functioning in Korean immigrants with asthma or chronic obstructive pulmonary disease (COPD). METHODS: Outpatients with asthma or COPD participated in this cross-sectional, correlational study. Symptoms, dyspnea, mood, and functional performance were assessed with questionnaires. Descriptive and inferential statistics were used to analyze the data. RESULTS: The most frequently reported symptom was shortness of breath. Three factors emerged from 16 symptoms. Age, mean severity score of 7 symptoms, working status, level of acculturation, and level of education explained significant variance in functional performance. CONCLUSION: The symptom cluster, consisting of 7 symptoms, showed the greatest effect on levels of functioning, which emphasizes the importance of assessment for coexisting symptoms in populations with these diseases. PMID- 22054720 TI - Medication adherence mediates the relationship between marital status and cardiac event-free survival in patients with heart failure. AB - OBJECTIVE: Prognosis is worse in unmarried patients compared with married patients with heart failure (HF). The reasons for differences in outcomes are unclear, but variations in medication adherence may play a role, because medication adherence is essential to achieving better outcomes. The study objective was to determine whether medication adherence mediated the relationship between marital status and cardiac event-free survival in patients with HF. METHODS: Demographic, clinical, and psychosocial data were collected by questionnaires and medical record review for 136 patients with HF (aged 61 +/- 11 years, 70% were male, 60% were in New York Heart Association class III/IV). Medication adherence was monitored objectively for 3 months using the Medication Event Monitoring System. Cardiac event-free survival data were obtained by patient/family interview, hospital database, and death certificate review. A series of regression and Cox survival analyses were performed to determine whether medication adherence mediated the relationship between marital status and event-free survival. RESULTS: Cardiac event-free survival was worse in unmarried patients than in married patients. Unmarried patients were more likely to be nonadherent and 2 times more likely to experience an event than married patients (P = .017). Marital status was not a significant predictor of event-free survival after entering medication adherence in the model, demonstrating a mediation effect of adherence on the relationship of marital status to survival. CONCLUSION: Medication adherence mediated the relationship between marital status and event-free survival. It is important to design interventions to increase medication adherence that take into account subgroups, such as unmarried patients, who are at higher risk for nonadherence. PMID- 22054721 TI - Spontaneous healing of posttraumatic focal coronary aneurysm: a case report. AB - We report on the spontaneous healing of a posttraumatic focal coronary aneurysm in a previously healthy 61-year-old man after his involvement in a motor vehicle accident, resulting in blunt chest trauma that injured the anterior wall of his left ventricle. Left-sided cardiac catheterization and selective coronary angiography 1 month after the accident showed an aneurysm in the proximal part of the left anterior descending artery, and normal coronary arteries otherwise. Intravascular ultrasound revealed that the lesion was a pseudoaneurysm protruding toward the myocardium. Surgical removal of the aneurysm was not considered, and the patient was discharged after 2 months of uneventful hospitalization. Follow up coronary angiography and intravascular ultrasound at 3 months and 1 year after the accident showed a total regression of the aneurysm. The patient has remained asymptomatic, with no residual ischemia 3 years after the accident. This case indicates that careful conservative treatment is a therapeutic option for posttraumatic coronary pseudoaneurysms. PMID- 22054722 TI - Lethal hemorrhagic alveolitis after adenovirus pneumonia in a lung transplant recipient. AB - Viral infections are frequent and severe in lung transplant recipients. They frequently occur during the first year after transplantation. We report on a rare case of bilateral adenovirus necrotizing pneumonia with a diffuse alveolar hemorrhage, 4 years after bilateral lung transplantation. The medical evolution was lethal in 72 hours because of respiratory, renal, and cardiac failure. Considering this case and the growing evidence on the severity of adenoviral infections, we call for controlled studies and therapeutic recommendations. PMID- 22054723 TI - Effect of coronary revascularization on serum collagen biomarkers and left ventricular remodeling in patients with acute myocardial infarction. AB - OBJECTIVE: After an acute myocardial infarction (AMI), early coronary revascularization alleviates the synthesis of cardiac collagen and ventricular remodeling. However, the impact of late coronary revascularization on the synthesis of myocardial collagen or on serum collagen biomarkers is unknown. This study aimed to investigate the effects of late coronary revascularization on serum collagen biomarkers after AMI. METHODS: Forty-five patients were divided into early (n = 20) and late (n = 25) coronary revascularization groups. The early coronary revascularization group received either successful percutaneous coronary intervention (PCI) or thrombolytic therapy within 6 hours of their myocardial infarction (MI), whereas the late PCI group received PCI between 12 and 14 days after their MI. Serum type I procollagen (PICP) and type III procollagen (PIIINP) were measured by radioimmunoassay. RESULTS: In the early coronary revascularization group, the amount of serum PICP on days 60 and 180 was similar to that of week 1 (P > .05). The PICP on days 90 and 180 in the late coronary revascularization group was higher than in the early coronary revascularization group at the same time point (P < .05). No significant difference was evident in mean serum PIIINP between the two groups on day 60 or 180 after the MI (P < .05). CONCLUSION: Late coronary revascularization in patients with acute ST-elevation MI was associated with an elevation in serum PICP. Early coronary revascularization should be performed in patients with ST elevation, to alleviate myocardial remodeling. PMID- 22054724 TI - Factors associated with delayed care-seeking in hospitalized patients with heart failure. AB - OBJECTIVE: This study sought to evaluate the contributions of symptom recognition and clinical factors to delays in care-seeking. METHODS: A descriptive correlational study design was used to study 75 patients (mean age, 74.7 years; SD, 10.86 years; range, 40 to 96 years) admitted to a tertiary-care medical center with recurrent symptoms (New York Heart Association classes 2 to 4). The sample was 52% male and 85.3% white. The Heart Failure Somatic Perception Scale (HFSPS) was used to examine symptoms, and additional data were collected on physiologic, social, and demographic factors. RESULTS: The mean HFSPS score was 37.52 (range, 2 to 74; possible range, 0 to 90). Subjects reported 2 to 16 out of 18 possible symptoms. Durations of individual symptoms ranged from 5 minutes to 8 years, with individual patients describing a variety of symptom combinations and multiple time frames, depending on the specific symptom. Most subjects (80%) reported a mixture of acute and chronic symptoms. A pattern of chronic vs. acute symptoms was associated with proactive vs. emergent care-seeking, respectively. The HFSPS scores did not correlate with care-seeking behavior. CONCLUSION: Symptom recognition is a complex phenomenon, and few factors differentiate emergent from proactive care-seeking. PMID- 22054725 TI - Response to pulmonary vasodilator treatment in a former smoker with combined interstitial lung disease complicated by pulmonary hypertension: case report and review of the literature. AB - We describe a 76-year-old former smoker with a diagnosis of combined pulmonary fibrosis and emphysema associated with pulmonary hypertension and rapidly progressive right heart failure, in whom combined treatment with sitaxsentan and sildenafil resulted in sustained improvement of his clinical condition and exercise performance, without any relevant adverse events. Combined pulmonary fibrosis and emphysema comprises a recently identified syndrome, probably related to tobacco use, and characterized by the coexistence of upper-lobe emphysema and fibrotic changes of the lower lobes, preserved lung volumes, significant hypoxemia, and a high prevalence of pulmonary hypertension, resulting in severe dyspnea. To date, no prospective series, to the best of our knowledge, has reported on the effects of pulmonary vasodilator therapy in such patients. PMID- 22054726 TI - The optimal dose of recombinant human osteogenic protein-1 enhances differentiation of mouse osteoblast-like cells: an in vitro study. AB - OBJECTIVE: There is no certain conclusion on the effect of recombinant human Osteogenic Protein-1 (OP-1, BMP-7) on the proliferation of the osteoblast-like cell line, MC3T3-E1. Furthermore, the optimal dose of rhOP-1 on cell differentiation still needs to be elucidated. This investigation aims to delineate the biofunctional characteristics of rhOP-1 in inducing osteoblastogenesis of MC3T3-E1 through in vitro time-course and dose-response studies. DESIGN: MC3T3-E1 cells were cultured for 1, 4, 7 days with the addition of different rhOP-1 concentrations (0, 10, 20, 50, 100, 200, 400 ng/ml), and cell proliferation and cell differentiation were examined. RESULTS: MC3T3-E1 cell proliferation was stimulated by rhOP-1 in a dose-dependent manner (0-400 ng/ml) on day 1, whereas on day 4 and 7, it was still stimulated at low concentrations (10, 20, 50 ng/ml) but inhibited at high ones (200, 400 ng/ml). The alkaline phosphatase (ALP) activity, osteocalcin (OC) production, collagen deposition and extracellular matrix mineralization were dramatically elevated by rhOP-1 treatment, as a function of culture time and rhOP-1 concentration, and all of them reached a plateau at the concentration of 200 ng/ml. Real-time quantitative RT-PCR results showed Runx2, AKP-2, OC and Nog mRNA expressions increased in a dose- and time-dependent manner, and their expressions were significantly higher at high rhOP-1 concentrations than that of low ones. No significant differences were found between the effects of 200 ng/ml rhOP-1 and 400 ng/ml rhOP-1 on the differentiation of MC3T3-E1 cells, except the expression of Nog mRNA, whose expression level was much higher at 400 ng/ml than that at 200 ng/ml. CONCLUSIONS: These results suggest that cell proliferation of MC3T3-E1 is depended on culture time and rhOP-1 concentration, rhOP-1 could stimulate the differentiation of MC3T3-E1 cells and the optimal concentration could be 200 ng/ml. PMID- 22054727 TI - Isolation and characterization of probiotic strains for improving oral health. AB - Probiotics have been proven effective for preventing caries. In contrast, the effect of probiotics on improving oral diseases such as gingivitis, periodontitis and halitosis has been less explored. OBJECTIVE: To perform a screening of lactic acid bacteria, according to international guidelines for the evaluation of probiotics, in order to select candidate probiotic strains for preventing oral disorders. STUDY DESIGN: The strains were isolated from healthy children and were subjected to a variety of in vitro tests in order to show their functionality. The safety of the strains was assessed by determining antibiotic susceptibility and production of lactic acid. RESULTS: Forty-six of the 100 new isolates were assigned to lactic acid bacteria genera after a biochemical characterization. Most of the new isolated strains seem to be resistant to oral conditions, have great ability to form aggregates and have high antagonistic activity against oral pathogens. None of the strains produced unpleasant volatile compounds. The strains showed high ability to adhere to oral tissues and they do not present any antibiotic resistance. Moreover, an increased risk of developing caries due to their ability to produce lactic acid was discarded in seven pre-selected probiotic candidates. CONCLUSIONS: These lactic acid bacteria show promising properties to be used as potential probiotics for improving oral health. PMID- 22054728 TI - Hurdles toward a cure for CML: the CML stem cell. AB - Chronic myeloid leukemia (CML) is the first cancer in which a genetic alteration was proven to be of pathogenic significance and is considered a disease model for oncogene addiction, targeted therapy, and cancer stem cells (CSCs). The introduction of tyrosine kinase inhibitors (TKIs) resulted in dramatic improvement in response and survival for patients with CML in chronic phase (CP); however, CSCs are spared by TKIs. In this article, we review the role of CSCs in CML in CP, their persistence following TKI treatment, and current approaches to target this population in an attempt to achieve disease cure. PMID- 22054729 TI - The biology of chronic myelogenous leukemia progression: who, what, where, and why? AB - Before the days of transplantation and tyrosine kinase inhibitor therapy, all cases of chronic myelogenous leukemia would inevitably proceed from chronic phase through accelerated and blast crisis, implying that there is a program of progression set in motion by unopposed BCR-ABL activity. Since then, much work has identified a plethora of genetic changes associated with progression, the common themes being changes in self-renewal, differentiation, and deregulation of apoptotic pathway. Some of the genes and pathways uncovered offer some progress for research on novel therapy for blast crisis. PMID- 22054730 TI - Chronic myeloid leukemia: mechanisms of resistance and treatment. AB - Imatinib mesylate has revolutionized the treatment landscape for patients with newly diagnosed chronic myeloid leukemia. Follow-up has shown excellent response rates, progression-free survival, and overall survival after 8 years. However, some patients develop resistance to imatinib treatment because of a multitude of reasons. Strategies to overcome resistance include dose escalation of imatinib or switching to a second-generation tyrosine kinase inhibitor or to one of the newer non-tyrosine kinase inhibitors. This article guides the treating physician with a rational approach in the management of patients with chronic myeloid leukemia who fail initial treatment with imatinib or lose response while on therapy with imatinib. PMID- 22054731 TI - BCR-ABL mutations in chronic myeloid leukemia. AB - The advent of imatinib has been a major breakthrough in chronic myeloid leukemia (CML) treatment. A few patients treated with imatinib are either refractory to imatinib or eventually relapse. Resistance is frequently associated with mutations in the kinase domain of BCR-ABL. Over 100 point mutations coding for single amino acid substitutions in the BCR-ABL kinase domain have been isolated from CML patients resistant to imatinib treatment. Most reported mutants are rare, whereas 7 mutated residues comprise two-thirds of all mutations detected. BCR-ABL mutations affect amino acids involved in imatinib binding or in regulatory regions of the BCR-ABL kinase domain, resulting in decreased sensitivity to imatinib while retaining aberrant kinase activity. The early detection of BCR-ABL mutants during therapy may aid in risk stratification as well as molecularly based treatment decisions. PMID- 22054732 TI - Selection of therapy: rational decisions based on molecular events. AB - This article reviews to what extent molecular data can be used to rationalize therapeutic choices in the treatment of chronic myeloid leukemia. Two categories of data are discussed: markers that globally measure risk but do not provide a molecular rationale for therapy selection; and biomarkers with a causal link to a clinical phenotype, such as certain mutations of the BCR-ABL kinase domain. As therapy selection is still mainly based on clinical criteria, molecular biomarkers are discussed in the context of available clinical prognostication tools, focusing on biomarkers that do not reflect disease burden as a surrogate of responsiveness to treatment. PMID- 22054734 TI - Portal vein thrombosis and budd-Chiari syndrome. AB - Venous thrombosis results from the convergence of vessel wall injury and/or venous stasis, known as local triggering factors, and the occurrence of acquired and/or inherited thrombophilia, also known as systemic prothrombotic risk factors. Portal vein thrombosis (PVT) and Budd-Chiari syndrome (BCS) are caused by thrombosis and/or obstruction of the extrahepatic portal veins and the hepatic venous outflow tract, respectively. Several divergent prothrombotic disorders may underlie these distinct forms of large vessel thrombosis. While cirrhotic PVT is relatively common, especially in advanced liver disease, noncirrhotic and nontumoral PVT is rare and BCS is of intermediate incidence. In this article, we review pathogenic mechanisms and current concepts of patient management. PMID- 22054733 TI - Chronic myelogenous leukemia: role of stem cell transplant in the imatinib era. AB - In the pre-tyrosine kinase (TKI) era, allogeneic stem cell transplant (allo-SCT) was the front-line treatment of choice for young patients with chronic myelogenous leukemia (CML). Today, imatinib is well established as front-line therapy for CML, with excellent long-term outcomes. This has changed the role of allo-SCT and the number of patients undergoing allo-SCT has declined dramatically. Allo-SCT is currently recommended for patients in accelerated/blast phase disease, those who have failed a second-generation TKI and those with TKI resistant mutations such as T315I. The role of allo-SCT in the management of CML will require continual reappraisal as medical therapies continue to evolve. PMID- 22054735 TI - Systemic mastocytosis. AB - An unusual disease, mastocytosis challenges the pathologist with a variety of morphologic appearances and heterogeneous clinical presentations ranging from skin manifestations (pruritus, urticaria, dermatographism) to systemic signs and symptoms indicative of mast cell mediator release, including flushing, hypotension, headache, and anaphylaxis among others. In this article, we focus on recognizing the cytology, histopathology, clinical features, and prognostic implications of systemic mastocytosis, a clonal and neoplastic mast cell proliferation infiltrating extracutaneous organ(s) with or without skin involvement. Diagnostic pitfalls are reviewed with ancillary studies to help unmask the mast cell and exclude morphologic mimics. PMID- 22054736 TI - Diagnosis of myelodysplastic syndromes in cytopenic patients. AB - Sustained clinical cytopenia is a frequent laboratory finding in ambulatory and hospitalized patients. For pathologists and hematopathologists who examine the bone marrow (BM), a diagnosis of cytopenia secondary to an infiltrative BM process or acute leukemia can be readily established based on morphologic evaluation and flow cytometry immunophenotyping. However, it can be more challenging to establish a diagnosis of myelodysplastic syndrome (MDS). In this article, the practical approaches for establishing or excluding a diagnosis of MDS (especially low-grade MDS) in patients with clinical cytopenia are discussed along with the current diagnostic recommendations provided by the World Health Organization and the International Working Group for MDS. PMID- 22054737 TI - Chronic myelogenous leukemia. Preface. PMID- 22054738 TI - Governing through problems: the formulation of policy on amphetamine-type stimulants (ATS) in Australia. AB - Producing and implementing credible and effective policies on illicit drug use is generally seen as an important aspect of health governance in the West. Yet the controversy surrounding illicit drug use means this is no easy task. With public opinion perceived by policy makers to be set against illicit drug use, and understandings of its effects tending towards generalisation and pathologisation, the need for timely and rational responses is considered self evident. These responses are, however, regularly criticised as driven as much by electoral politics and expedience as by research findings or expert opinion. Destined to receive close critical scrutiny from all sides, these policies, and the processes undertaken to develop them, are obliged to negotiate a complex political domain. Despite this scrutiny, and the pressure it brings to bear on the policy-making process, little scholarly attention has been paid to the area to date. In this article, we examine in detail one important area of illicit drug policy - the use of amphetamine-type stimulants (ATS) in Australia. We draw on the international critical literature on the ATS problem to situate our analysis. We note that ideas of 'panic', including Cohen's notion of moral panic, have been used here to good effect, but, aiming to acknowledge the complexities of policy, we turn to poststructuralist methods of policy analysis to pursue a different approach. Following Bacchi's observation that 'we are governed through problematisations rather than policies' (2009, p. xi), we ask how the problem of ATS use has been formulated in policy. We examine key state and national policy documents, and two central themes found in them - causation and evidence - to identify the specific strategies used to authorise the recommendations and measures presented as following from the problem of ATS use. In doing so, we clarify important ways in which policy may at times work to obscure the limits of its legitimacy. PMID- 22054739 TI - The politics of visibility: Drug users and the spaces of drug use. PMID- 22054740 TI - The effect of different methods of electrical stunning of lambs on blood pressure and muscular activity. AB - The effect on blood pressure and muscular activity of a 'head-only' and a 'head to-body' method of electrical stunning was measured in groups of lambs. A two- to three-fold increase in arterial pressure followed 'head-only' stunning, along with moderate increases in venous pressure. By contrast, after 'head-to-body' stunning, arterial pressure decreased, but venous pressure increased to above 50 mm Hg. Electromyographic recordings showed there was a greater increase in the intensity of muscular activity following 'head-to-body' stunning compared with 'head-only' stunning and there was a direct correlation between the degree of muscular activity and the increase in venous pressure. It is argued that the resultant pressure changes in the microcirculatory bed are likely to be associated with the occurrence of haemorrhagic defects following stunning by electrical methods. PMID- 22054741 TI - Stability at comminution chopping temperatures of model chicken breast muscle emulsions. AB - Mixtures of vegetable oil and protein solutions extracted from chicken breast muscle were heated to 10 degrees C, 20 degrees C and 30 degrees C before or after the Omni-mixer step of timed emulsification. Emulsion stability (ES) was determined by placing the extracted cream layer between layers of filter paper and polyester mesh and measuring the weight loss after 96 h at 0-1 degrees C. All natural actomyosin and exhaustively washed chicken breast muscle emulsions lost no more than 50% of their original weight after heating and were defined as being stable. Even excessive chopping temperatures (30 degrees C) failed to effect timed emulsification or ES. This study suggests that any instability of finished commercial sausage-type products is not due to changes in the protein caused by excessively high chopping temperatures generated during comminution. PMID- 22054742 TI - Stability at cooking temperatures of model chicken breast muscle emulsions. AB - Emulsion stability (ES) was measured on timed emulsification (TE) samples made with natural actomyosin (NAM) and exhaustively washed (EW) muscle, heated to 75 degrees C, before using the Omni-mixer or after centrifugation. All emulsions cooked after centrifugation were found to be stable. The emulsions made with NAM showed a large decrease in ES when heated above 40 degrees C prior to using the Omni-mixer. However, aqueous protein disappearance did not decrease significantly after TE until NAM was heated to between 60 degrees C and 75 degrees C. On the other hand, emulsions made with EW muscle heated prior to using the Omni-mixer showed a large decrease in both ES and aqueous protein disappearance after TE between 60 degrees C and 75 degrees C. PMID- 22054743 TI - Z-disc digestion of isolated bovine myofibrils by an endogenous calcium activated neutral proteinase. AB - Calcium activated neutral proteinase (CANP) activity has been purified from bovine M. semimembranosus. The effect of the enzyme on purified fractions of beef myofibrils is described. The Z-discs were the main target of the enzyme; small holes developed and the Z-discs were fragmented into smaller units of equal size. The Z-discs fragments were also split transversely, leaving half to each of the neighbouring sarcomeres. Prolonged digestion removed the entire Z-discs and its set of thin myofilaments. The functional importance of the proteinase in meat tenderization is discussed. PMID- 22054744 TI - Thermomechanical properties of beef muscle. AB - Differential scanning calorimetry (DSC) was used to follow the three major endothermic transitions (T(1), T(2) and T(3)) of beef muscle during heating. Borchardt and Daniels reaction kinetics were used to predict the three time and temperature treatments required to sequentially eliminate each transition. Longissimus dorsi and semimembranosus muscles were removed from beef carcasses suspended by Achilles tendon or pelvis. Samples prepared by heating for 5 min at 57 degrees C (I), 70 degrees C (II) and 81 degrees C (III) were assessed by sensory panel for tenderness, juiciness and residual connective tissue. Weight loss, Warner-Bratzler (W-B) shear and microstructure using transmission electron microscopy (TEM) were also determined. The I treatment showed a significant difference in tenderness and residual connective tissue between muscles, but not between contraction states. The II treatment produced collagen shrinkage and a significant drop in W-B shear and residual connective tissue, coupled with increased tenderness in semimembranosus muscle. An increased W-B value, decreased juiciness, increased weight loss and a reduction in sarcomere and A-band length accompanied the III transition. Muscles from carcasses that had been suspended by the pelvis were found to be significantly more tender than the same muscles from Achilles hung carcasses. It is concluded that DSC is capable of determining amount of protein denaturation and, hence, degree of cooking. PMID- 22054745 TI - Cholesterol content of muscle and adipose tissue from crossbred bulls and steers. AB - Cholesterol content (mg/100g wet weight) of muscle and adipose tissue from crossbred bulls (N = 34) and steers (N = 35) was determined by spectrophotometry. Sampling site effects were highly significant, with subcutaneous adipose tissue (101.7) and perinephric adipose tissue (89.7) containing the most cholesterol, and longissimus muscle (58.3) containing the least. Semitendinosus and triceps brachii muscles were similar in cholesterol content (63.9 mg/100g and 63.7 mg/100g, respectively). Although sex condition differences within sampling sites were non-significant, steer carcasses may have more total cholesterol than bull carcasses because steers contain a higher percentage of fat than bulls raised under similar conditions. PMID- 22054746 TI - Sensitivity to ionic strength of Mg?Ca-enhanced ATPase activity as an index of myofibrillar ageing in beef. AB - Modifications of Mg?Ca-enhanced ATPase activity and its sensitivity to ionic strength were studied during the conditioning of beef Longissimus dorsi muscle, together with the changes in the mechanical properties of the myofibrillar structure assessed instrumentally by a compressive test. As the storage time increases, the ATPase activity increases at low ionic strengths whereas it decreases at higher ones. Concomitantly, we observe an increment, with storage time, in the slope of the straight line graph obtained when plotting this ATPase activity against KCl concentrations. This slope enhancement is parallel with the decrease in the maximum compressive strength. Furthermore, these two changes have been significantly correlated (P < 0.01). We conclude that the slope value which quantifies the sensitivity of the ATPase activity to ionic strength could be an accurate indicator of the degree of ageing of the myofibrillar structure and has been called the Biochemical Index of Myofibrillar Ageing (BIMA). PMID- 22054747 TI - The fate of the large proteins of the myofibril during tenderising treatments. AB - Changes in the large structural proteins of the myofibril, during treatments which affect tenderness, have been followed using SDS-PAG electrophoresis. Despite the known decay of gap filaments during ageing, and the identification of connectin as their substance, connectin survives prolonged ageing at 15 degrees C (although it succumbs at temperatures at which it denatures). Cold shortening or stretching of muscle does not affect autolysis, except in the prolonged ageing of stretched samples, where myosin 'heads' are apparently detached due to their greater accessibility to proteases. The only two changes on the same time scale as tenderisation are the disappearance of nebulin and an increase in a protein lying between connectin and nebulin on the gels. The evidence for nebulin as the N(2)-line protein is questionable, and it is proposed that it may instead be a component of the G-filaments, necessary for their stability. In pressure-heat (P H) treatment at 50 or 55 degrees C, which reduces yield point rather than shear force, connectin survives, while nebulin is partly destroyed. A tenderising P-H treatment at 60 degrees C degrades both. Cooking to various degrees apparently causes a random splitting of connectin, revealed as a smear down the gels. After cooking at 80 degrees C a little of the original band survives, while most of the smear represents material with a molecular weight above half a million, and should therefore still be capable of contributing to structural strength. Prior tenderising treatments have little effect on gels derived from material cooked at 80 degrees C, although what remains of the sharp connectin band in cooked controls disappears in aged or P-H treated samples. PMID- 22054748 TI - Utilization of chickpea flour in sausages. AB - 'English' type fresh skinless sausages were prepared in which some of the meat (mutton, pork or beef) was replaced on a protein to protein basis by chickpea flour. The acceptability of mutton sausages containing chickpea flour was not affected at levels of substitution up to 40%, whereas pork and beef sausages were significantly less acceptable at substitution levels above 30%. In all the sausages incorporation of chickpea flour led to increased cooking losses and softer textures. Incorporation of chickpea flour caused discoloration of the raw sausages which became more prominent during storage at 0 degrees C. PMID- 22054749 TI - The biochemical basis of fibre types in bovine muscle. AB - Recent studies using isolated muscle fibres have established a link between the histochemical fibre types, I, IIA and IIB, which can be defined by myofibrillar ATPase activity, and three forms of myosin heavy chain. This work is reviewed, as is work on metabolic variability within these fibre types. Results are them presented which show that the activity of myofibrillar ATPase in sections, although principally determined by the myosin heavy chain, is modified by other myofibrillar components, as yet unidentified. Evidence is also presented for hybrids of myosin heavy chain in muscle fibres. Finally, metabolic variability within the fibre types is examined for bovine muscle. It is concluded that, in spite of wide metabolic variability within types, a classification based on myofibrillar ATPase activity is still useful. PMID- 22054750 TI - Effect of castration on bovine muscle composition. AB - Samples of bovine muscles were cross-sectioned and stained for myofibrillar ATPase. Three fibre types were distinguished, I, IIA and IIB. In the longissimus dorsi (LD) muscles of steers the average occurrence of IIB fibres was 32%, but in bulls was only 8%. The difference was highly significant. In contrast, the average occurrence of I fibres in steers and bulls was not significantly different. IIB fibres were generally rare in splenius (Sp) muscle, and occurred in some steers but in no bulls. That IIB fibres were more common in steer muscle was confirmed by studies with pairs of identical twins. The increased occurrence of IIB fibres in steers was unrelated to carcass weight changes often associated with castration. Fibre type occurrence data in steer or bull muscles were highly variable. Also, muscles of twins remained macroscopically similar in spite of significant maleness differences between two animals of a pair. Together, these results indicate that castration exerted a relatively minor, but nonetheless significant, effect on the muscles studied. Other factors, such as breed, apparently exert greater effects: LD muscles of Sahiwal * Friesian bulls (a tropical-temperate cross) were very steer-like in composition. Areas of fibres increased with carcass weight. For LD, areas increased with similar slopes in steers and bulls, but for Sp, areas in bulls increased with steeper slopes. This difference related to the increased development of muscles about the neck in bulls. Further, in heavier bulls, areas of IIA fibres were significantly larger than areas of I fibres. Evidence is presented which suggests that the paucity of IIB fibres in bulls and the disproportionate area increases of IIA fibres in bull Sp, relate to the serum concentrations of androgens, which differ markedly in steers and bulls. Possible modes of action of androgens are discussed. PMID- 22054751 TI - Biologic response modifiers: relevance & repercussions. AB - Biologic response modifiers (BRMs) are substances that occur naturally in the body. They can also be manufactured in the laboratory and then administered as targeted therapy. Undoubtedly BRMs will find expanded role in terminal illness like cancer where other therapies have failed. However, great caution must be exercised in prescribing these agents in chronic indolent diseases where potential for ultimate harm might outweigh short-term benefits. PMID- 22054752 TI - Overview of biologic response modifiers in infectious disease. AB - The conventional treatment of infectious agents is increasingly encountering antimicrobial resistance. This resistance has led to an intense search for novel treatment modalities for infectious diseases. Elucidation of the mechanisms underlying the inhibitory activity of chemokines has been instrumental in the rational design of anti-human immunodeficiency virus chemokine drugs. The immune based therapies, in combination with antimicrobial drugs, for viral hepatitis have attracted much attention. Recognition of toll-like receptors by synthetic immunomodulators is used for certain viral infections. New methodologies have the potential to identify novel targets and foster the development of individually tailored immunomodulatory drug treatments. PMID- 22054753 TI - Role of endogenous biological response modifiers in pathogenesis of infectious diseases. AB - Biologic response modifiers (BRMs) interact with the host immune system and modify the immune response. BRMs can be therapeutically used to restore, augment, or dampen the host immune response. Although they have been used for decades, their clinical applications have been expanded in the past decade for diagnosis and treatment of many diseases including cancers, immunologic disorders, and infections. This article discusses endogenous biological response modifiers (ie, naturally occurring immunomodulators as a part of the host immune system), which play vital roles as regulators of both innate and adaptive immune responses. PMID- 22054754 TI - Vaccines and vaccine adjuvants as biological response modifiers. AB - Vaccines have been used successfully for many years to prevent death and morbidity from infectious diseases. In the last two decades major advances in the fields of genetics and immunology have allowed a significant increase in the use of immunomodulatory drugs in a broad range of pathologic conditions. This article reviews several uses of immunomodulating properties of vaccines, both old and new, with a focus on cancer and autoimmune diseases. Special emphasis is placed on the historical aspects and current applications of the bacillus Calmette Guerin vaccine, the first vaccine to be used in cancer immunotherapy. PMID- 22054755 TI - Polyclonal immunoglobulins and hyperimmune globulins in prevention and management of infectious diseases. AB - Immunoglobulin therapy has a rich history of use in preventing and treating infectious diseases; however, clinical data on the efficacy of immunoglobulin is lacking for many infectious diseases. Immunoglobulin therapy is routinely used in postexposure prophylaxis for bacterial infections, including tetanus, botulism, and diphtheria, and viral infections, including hepatitis A and B and varicella. Immunoglobulin therapy has also been used in many severe and life-threatening infections where treatments are limited, including toxic shock syndrome, respiratory syncytial virus infection, and cytomegalovirus infection. The authors review the evidence for the use of immunoglobulin therapy in common adult infectious diseases. PMID- 22054756 TI - Monoclonal antibodies in infectious diseases: clinical pipeline in 2011. AB - Of the more than 20 monoclonal antibodies (mAbs) generated to combat infectious diseases (ID) that are in clinical development in 2011, most are in phase 1 or 2 and are directed against either viruses or bacterial toxins. Several high-profile anti-ID mAbs have recently failed in clinical trials. Despite the advancement in recombinant engineering technologies, anti-ID mAbs have yet to deliver on their promise as "magic bullets," especially against nosocomial infections. A paradigm shift in favor of developing mAb combinations, which act synergistically with each other or with small molecule drugs, may be required to move the field forward. PMID- 22054757 TI - Colony-stimulating factors in the prevention and management of infectious diseases. AB - Colony-stimulating factors (CSFs) are attractive adjunctive anti-infective therapies. Used to enhance innate host defenses against microbial pathogens, the myeloid CSFs increase absolute numbers of circulating innate immune effector cells by accelerating bone marrow production and maturation, or augment the function of those cells through diverse effects on chemotaxis, phagocytosis, and microbicidal functions. This article summarizes the evidence supporting the accepted clinical uses of the myeloid CSFs in patients with congenital or chemotherapy-induced neutropenia, and presents an overview of proposed and emerging uses of the CSFs for the prevention and treatment of infectious diseases in other immunosuppressed and immunocompetent patient populations. PMID- 22054758 TI - Interferons as therapeutic agents for infectious diseases. AB - This article explains the rationale for development of interferons as therapeutic agents, and describes commercial products available today. It also provides a summary of studies that have been performed with interferons for use as exogenous biological response modifiers in viral infections. Overall, the best data exist for treatment of viral hepatitis B and C, for which interferons are a cornerstone of therapy. Although infections with human papillomavirus and common cold viruses sometimes respond favorably to interferons, their outcomes are far from ideal. Finally, the role of interferons as vaccine adjuvants is still being explored but could be promising. PMID- 22054759 TI - Mediators of systemic inflammatory response syndrome and the role of recombinant activated protein C in sepsis syndrome. AB - The systemic inflammatory response syndrome, the host's response to infection involves a series of cascading events that mobilize a series of mediators involving the immune system, complement, and the coagulation cascade. Although the initial focus of mediators is to limit infection, this cascade may run amok and cause the development of hypotension, vascular instability, and disseminated intravascular coagulation, leading to morbidity and mortality in the host. Several therapeutic trials have focused on the modulation of these mediators, but use of recombinant human activated protein C in patients with severe sepsis is the only one that has shown a benefit in clinical trials. PMID- 22054760 TI - The common immunogenic etiology of chronic fatigue syndrome: from infections to vaccines via adjuvants to the ASIA syndrome. AB - Chronic fatigue syndrome (CFS) is characterized by unexplained fatigue that lasts for at least 6 months with a constellation of other symptoms. Most cases start suddenly, and are usually accompanied by a flu-like illness. It is a symptom based diagnosis of exclusion, the pathogenesis of which is unknown. Studies have examined and hypothesized about the possible biomedical and epidemiologic characteristics of the disease, including genetic predisposition, infections, endocrine abnormalities, and immune dysfunction and psychological and psychosocial factors. Recently, the AISA (autoimmune/inflammatory syndrome induced by adjuvants) syndrome was recognized, indicating the possible contribution of adjuvants and vaccines to the development of autoimmunity. PMID- 22054761 TI - Mycobacteria and biological response modifiers: two sides of the relationship. AB - With increasing use of biological response modifiers (BRMs) for various systemic inflammatory diseases there is a need to be vigilant about complications with the use of these therapies. It is important to have appropriate screening for the infections in patients requiring BRMs. However, many studies have reported benefits of certain BRMs in the treatment of infections such as tuberculosis as adjuncts. Continued research and technical advances in immunogenetics helps understand complex mechanisms in the usage of the BRMs. This article summarizes the different aspects of the relationship between mycobacterial infections and the use of various BRMs for inflammatory conditions. PMID- 22054762 TI - Biologics and infections: lessons from tumor necrosis factor blocking agents. AB - In the decade since tumor necrosis factor alpha (TNF-alpha) antagonists were first approved for clinical use, they have proven invaluable for the treatment of specific types of chronic inflammation. Currently licensed TNF blockers fall into two classes, monoclonal antibody (or antibody fragments) and soluble receptor. Although they are equally effective in rheumatoid arthritis and psoriasis, important differences have emerged with regard to efficacy in granulomatous inflammation and risks of granulomatous infections, particularly tuberculosis. This article focuses on recent studies that inform prevention and management of infections in this susceptible patient population. PMID- 22054763 TI - Biological response modifiers (BRMs) are often discussed with a narrow focus on the"biological therapies," ie, the pharmacologically administered form of cytokines, eg, interferon or antagonists of cytokines, eg, tumor necrosis factor blocking agents. Introduction. PMID- 22054764 TI - A model for the thermal conductivity of frozen meat. AB - Even though extensive work on the experimental determination of the thermal conductivities of foodstuffs at different temperatures has been published, only a few predictive models for this important property have been developed. Calculation of freezing times in foods, such as meat, over the range from -1 degrees C to -30 degrees C, requires the use of mathematical models in which information on the thermal conductivity of partially frozen meat as a function of ice content in the tissue is provided. In the present paper a model for the thermal conductivity of meat as a function of temperature, which also accounts for its anisotropic properties, is proposed. Both directions, parallel and perpendicular to meat fibres, are considered and the model applies to unfrozen as well as to partially frozen meat. Results show good agreement with published experimental data obtained by a steady state method for different temperatures. PMID- 22054765 TI - Effect of cooling rate upon processing characteristics of pork meat of different glycolysis type during post mortem ageing. AB - Rapid chilling was applied to porcine longissimus dorsi muscles at 1 h post mortem in order to observe its effect on the quality of canned products prepared from those of different pH(1) values. The muscle from one side of each animal was removed from the carcase 50 minutes post mortem and divided into two longitudinal strips. One was chilled immediately to 13-15 degrees C (1 h post mortem): the other after a further hour (2 h post mortem) acted as control. After the centre temperature had reached 10 degrees C the muscles were stored in a refrigerator at 3-5 degrees C. Compared with the control samples (chilled at 2 h p.m.), rapid chilling from 1 h p.m. caused an improvement in the water-holding capacity and the texture of pork meat, which had higher pH(1) values and was processed at 2, 4 and 48 h p.m. There was minimum brine retention and texture score if samples-both rapidly chilled and control-were processed at 24 h p.m. Although brine retention of PSE pork meat could not be increased even by rapid chilling, the texture of heat treated PSE pork showed an improvement during storage, which was more pronounced after ageing for 48 h, if PSE samples were chilled at 1 h p.m. PMID- 22054766 TI - Comparison of isolated sarcoplasmic reticulum from bovine and rabbit muscle. AB - Comparison of the ultrastructure of purified bovine sarcoplasmic reticulum (SR) vesicles isolated from bovine sternomandibularis muscle before and following cold shortening indicates that the decreased Ca(2+)-accumulating ability and increased release of Ca(2+) in cold shortened muscle are not associated with any apparent structural alterations. Sodium dodecyl sulphate (SDS)-gel profiles revealed that the major constituent in both bovine and rabbit SR was Ca(2+)-activated ATPase with a molecular weight of 100,000-105,000. Both SR preparations also showed a proteolipid band at a molecular weight of approximately 10,000. Purified rabbit SR contained three protein components with molecular weights of 75,000, 60,000 and 53,000, whereas bovine SR exhibited a series of five components with molecular weights of 80,000, 66,000, 63,000, 50,000 and 45,000. Although the functions of these isolated proteins were not determined, it is assumed that at least some of them bind Ca(2+) ions in the SR. PMID- 22054767 TI - Effects of freezing, thawing and storage on some quality factors for portion-size beef cuts. AB - Portion-size beef cuts packaged in oxygen impermeable plastic bags were used to study the effects of rates of freezing and thawing, and storage time and temperature on drip and cooking losses, shear force, destruction of glutathione and accumulation of protein-breakdown products in meat. Portions weighing 150 g or over and frozen in an air-blast at -30 degrees C gave lower losses of drip and lower amounts of nitrogenous constituents in drip than samples weighing less than 150 g or samples frozen in cardboard boxes in still air at -18 degrees C. Freezing and thawing or frozen storage had no significant effect on shear force of meat frozen after ageing. During frozen storage, the destruction of glutathione and accumulation of protein-breakdown products increased, depending directly on storage temperature and time. The results show that a test based on these two biochemical changes would be suitable for assessing the quality of frozen beef. PMID- 22054768 TI - Cooking tenderizing in beef. AB - Heating tenderzes meat in three distinct phases. Up to 65 degrees C aging occurs through proteolysis at specific sites in the myofibrils. From about 70 degrees C the collagen of the connective tissue is denatured and melts. Above about 100 degrees C the myofibrils begin to break down again presumably from non-specific high-temperature hydrolysis. The rate of cooking tenderizing above 70 degrees C increases sharply with temperature and at 100 degrees C is equal to the maximum aging rate at 60 degrees C. However the collagen becomes more resistant to breakdown with animal age since the time to achieve maximum tenderizing of m. sternomandibularis at 80 degrees C increases from 4 h for young calves to greater than 15 h for old bulls. There is little overlap in the temperature ranges of aging and cooking tenderizing above 70 degrees C with a minimum tenderizing temperature of ~ 67 degrees C. The merits of tenderizing meat by holding it below or above this temperature are discussed. PMID- 22054769 TI - A note on the reduction in the iron content of meat in relation to iron deficiency. AB - The blood haemoglobin concentration, serum iron levels and muscle iron content of cattle, pigs, lambs and chickens were determined at the time of slaughter. There was a marked reduction in the iron content of pork, beef and chicken when compared with the figures quoted by McCance & widdowson (1960). The possible relationship between a reduction in the iron content of meat and the aetiology of iron deficiency is discussed. PMID- 22054770 TI - Studies on the meat production characteristics of Botswana goats and sheep-Part II: General body composition, carcase measurements and joint composition. AB - The present paper gives data on the general body composition, carcase size, weight and joint composition of indigenous Botswana goats and sheep of various age and sex groupings. Data on a small group of entire milk tooth male Boer goats are also presented. Indigenous male castrate goats developed larger and heavier carcases than sheep of a similar background with increasing age, although differences were not significant after correction for empty body weight (ebw). Castrate male indigenous sheep produced highest carcase and offal yields at the two tooth stage. Although mature female goats had significantly heavier ebws than the female sheep, the latter had significantly heavier carcases and heavier dressing out percentages (DO%) at equivalent ebws. The Boer goats had higher ebws, carcase weights and DO% than the indigenous goats of similar age while the indigenous castrates had larger and heavier carcases than the entires. The goats had proportionally heavier leg and shoulder joints whereas the sheep had heavier loins. PMID- 22054772 TI - Editorial. PMID- 22054771 TI - Effect of pressure treatments on the mechanical properties of pre- and post-rigor meat. AB - Pressure-heat treatment of beef semitendinosus samples post-rigor gave shear and tensile results similar to those obtained with pressure treatment pre-rigor. Post rigor pressure-heat treatment did not affect the contraction state, unlike pre rigor pressure treatment which caused samples to contract by about 40%. Maximum tenderizing effect by pressure-heat treatment (150 M Nm(-2) at 60 degrees C for 30 min) was achieved when samples were heated at 45 degrees C for 45-180 min immediately before application of the treatment. As the pre-pressurization temperature was increased, the duration of heating became more critical until at temperatures >= 60 degrees C the effects of subsequent pressure-heat treatment became very small. Pressure-heat treated samples did not show the increase in shear force values for cooking temperatures >= 60 degrees C associated with myofibrillar hardening. It was concluded that pressure-heat treatment primarily affected the myofibrillar structure. PMID- 22054773 TI - The influence of fibre-type composition and associated biochemical characteristics on the acid buffering capacities of several beef muscles. AB - Several beef forequarter muscles were investigated for fibre-type composition, total pigments, total nitrogen, non-protein nitrogen, anserine, carnosine and inorganic phosphorus contents, ultimate pH (pH(u)) and acid buffering capacities. In general, the predominantly 'red' fibre-type muscles had significantly higher (P<0.05) pH(u) values and total pigment concentrations than the predominantly 'white' fibre-type muscles which had significantly higher (P< 0.05) total nitrogen, non-protein nitrogen and carnosine contents and also significantly higher (P< 0.05) acid buffering capacities. The relationships between the various biochemical parameters of all the muscles studied and their acid buffering capacities were investigated by correlation matrix. The higher buffering capacities of the 'white' fibre-type muscles over the pH range pH(u) to pH 5.0 were attributed to their higher contents of carnosine and inorganic phosphorus. However, over the pH ranges pH(u) to pH 4.5 down to pH(u) to pH 3.0, the higher buffering capacities of the 'white' fibre-type muscles were attributed primarily to their higher lactic acid concentrations, as indicated by their low pH(u) values, and also to their higher non-protein nitrogen contents. PMID- 22054774 TI - Variations in water-holding capacity due to changes in the fibre diameter, sarcomere length and connective tissue morphology of some beef muscles under acidic conditions below the ultimate pH. AB - The water-holding capacities (WHC) of six different beef muscles were measured over the pH range 5.7 to 4.0. Corresponding changes in the morphology of muscle fibres and connective tissue were observed by light microscopy. WHC increased over the pH range 5.1 to 4.0 in all muscles, with the M. longissimus dorsi (LD) having significantly higher (p < 0.05) swelling ratios than the other muscles at pH 4.3 and pH 4.0. In all muscles, swelling increased across and along the muscle fibre axis between pH5.1 and pH4.4. However, towards pH4.0, increased muscle fibre swelling occurred in predominantly 'white' fibre-type muscles, in particular the LD, whereas muscle fibre shrinkage occurred in predominantly 'red' fibre-type muscles. Increased swelling of perimysial collagen and endomysial reticulin was observed in all muscles between pH4.5 and pH4.0, while the appearance of elastin was unaffected by pH. Consequently, interactions between muscle fibre swelling and connective tissue swelling determined the extent of total muscle swelling in different muscles between pH 4.5 and pH 4.0. PMID- 22054775 TI - Effects of ribose, xylose and arabinose on colour formation in processed meat products. AB - The effects of ribose, xylose and arabinose on colour formation of meat products processed by emulsion curing were investigated in an aqueous model system under anaerobic conditions. Ribose markedly enhanced the colour forming ability, nitrite decomposition and reducing ability, depending upon its initial concentration; and xylose and arabinose exhibited some promoting effects on them. The colour promoting effects of ribose, xylose and arabinose increased with a rise in pH, in agreement with the results for reducing ability. This suggested that the reducing ability of ribose, xylose and arabinose plays a key role in promoting colour formation of meat products in emulsion curing. PMID- 22054776 TI - Deformation of collagenous, elastin and muscle fibres in raw meat in relation to anisotropy and length ratio. AB - The influence of strain directions on the mechanical properties of raw meat samples in a compression test was analysed in relation to the contracted or stretched state and discussed in terms of connective network deformation. When the lateral deformation of a sample is in the direction of muscle fibres, the more the meat has been stretched ante-rigor, the smaller the strain range in which muscle fibres can be solicited alone and the lower the critical compression ratio at which collagenous fibres come under tension. Post-rigor contraction occurring in stretched muscles modifies the relations between muscle fibres and collagenous fibres and increases the critical compression ratio. The greatest post-rigor contractions have been observed in stretched slices of Semitendinosus and Lattissimus dorsi which are high elastin content muscles. This suggests that elastin has a major role in post-rigor contraction. In greatly contracted post rigor samples, as muscle fibres are wavy, they are not involved at low strains, likewise collagenous fibres around muscle fibres cannot be stressed until the waviness of muscle fibres has been removed. Therefore, in greatly contracted post rigor samples, the mechanical properties observed at low strains might belong mainly to elastin fibres. When the lateral deformation is perpendicular to the direction of muscle fibres these fibres are not involved and the more the meat has been stretched ante-rigor the higher the critical compression ratio. PMID- 22054778 TI - Professor mognes jul. PMID- 22054777 TI - Alternative methods of pig chilling. AB - Comparisons were made of the effect on cooling rate, weight loss, texture, bacterial numbers, drip and appearance of pork sides (average dead weight 75 kg) in refrigeration systems using high humidity (ice bank) or conventional chilling, both with and without a rapid pre-chill or delayed chilling, with and without a water spray. All treatments took between 15.7 and 19h post mortem to cool the deep leg of sides to 7 degrees C. Weight loss varied between 0.95% for sides in the delay and spray treatment to 2.17% for conventional chilling. The texture of the M. longissimus dorsi of sides from the rapid pre-chill and conventional chilling treatment was significantly tougher than from the other methods, including those from the rapid pre-chill and high humidity system. Variation in texture between animals within treatments was far greater than between treatments, and could not be explained by variations in cooling and glycolytic rate. There were no significant differences (P > 0.05) in bacterial numbers, drip and appearance between treatments. The choice of chilling system can be made on the basis of weight loss and capital and running costs. The delay and spray treatment would save L37 800 on an annual throughout of 3 080 tonnes of pork compared with a conventional system. PMID- 22054779 TI - Dr edgar C. Bate-smith. PMID- 22054780 TI - Evidence and outcomes in CKD. PMID- 22054782 TI - Differential effects of strict blood pressure lowering by losartan/hydrochlorothiazide combination therapy and high-dose amlodipine monotherapy on microalbuminuria: the ALPHABET study. AB - We investigated the effects of losartan/hydrochlorothiazide (HCTZ) fixed combination therapy and high-dose amlodipine monotherapy on BP measurements and target organ protection. In this open-label multicenter trial, hypertensive patients were randomly allocated to receive losartan 50 mg or amlodipine 5 mg for 4 weeks, and the treatments were changed to combination of losartan 50 mg/HCTZ 12.5 mg or amlodipine 10 mg for a further 4 weeks. A total of 91 hypertensive patients (age 63.6 years), 47 in the losartan/HCTZ group and 44 in amlodipine group, were enrolled. After 8 weeks, the clinic BP, home BP, and 24-hour ambulatory BP were successfully controlled to the same level in both treatment groups (P < .001). Furthermore, both groups showed the same degree of BP reduction in the 24-hour, daytime, and nighttime (P < .001). B-type natriuretic peptide (BNP) also significantly decreased to the same level in both groups, whereas the reduction of urinary albumin/creatinine ratio (UACR) was greater in the losartan/HCTZ group than in the high-dose amlodipine group (-47.6% vs 2.4%, P < .001). Losartan/HCTZ combination and high-dose amlodipine have similar effects on clinic, home, and ambulatory BP control and BNP reduction, whereas losartan/HCTZ has superior effect on UACR reduction when compared with high-dose amlodipine. PMID- 22054783 TI - Degradation of myofibrils from rabbit, chicken and beef by cathepsin l and lysosomal lysates. AB - The degradation of rabbit, chicken and beef myofibrils by cathepsin L or lysosomal lysates was studied by SDS-polyacrylamide-gel electrophoresis and electron microscopy (EM). Similar degradation patterns were observed for each myofibrillar preparation incubated with cathepsin L, except that myosin heavy chain and tropomyosin of beef were more susceptible than those of rabbit and chicken. Otherwise, troponin T, troponin in I and C-protein were rapidly degraded with slower degradation of titin, nebulin, myosin heavy chain, alpha-actinin, alpha-tropomyosin, actin and myosin light chains, LC1 and LC2. However, the component of 30 000 Mr was found to be further degraded to smaller peptides. Degradation at pH 5.5 (approximate post-mortem limit value) was faster than at pH 6.0 but slower than at pH 5.0. A number of new protein bands were identified (130 000, 120 000, 90 000, 85 000, 80 000, 31 000 and 30 000 Mr). The degradation patterns of rabbit myofibrils by rabbit muscle lysosomal lysates were similar to that of myofibrils incubated with purified cathepsin L except for the retention of the 30 000 Mr component and reduced degradation of actin, due presumably to the reduced amount or stability of cathepsin L in the crude enzyme preparations. Electron micrographs revealed that myofibrillar degradation by cathepsin L occurred preferentially at the Z-lines leading to removal of the Z-line proteins and fracturing of the myofibrils at these sites. Catheptic damage was seen to be most rapid in chicken myofibrils and least rapid in beef myofibrils consistent with the more rapid conditioning process in chicken. PMID- 22054781 TI - Association between circulating specific leukocyte types and incident chronic kidney disease: the Atherosclerosis Risk in Communities (ARIC) study. AB - Progressive renal fibrosis is a characteristic of all the diseases that cause renal failure and is invariably accompanied by a prominent leukocyte infiltration in the kidney. The goal of this study was to determine the association between the circulating specific leukocyte types and incident chronic kidney disease (CKD). In a cohort of 10,056 middle-aged white and African American adults, levels of circulating neutrophils, lymphocytes, and monocytes were measured at baseline; blood pressure (BP) and serum creatinine were measured and estimated glomerular filtration rate (eGFR) was calculated at baseline and 3 and 9 years later; and surveillance for first hospitalization or death with CKD was carried out over a mean follow-up of 7.4 years (maximum, 11.9 years). Increased neutrophil levels and decreased lymphocyte levels were significantly associated with greater CKD incidence after adjustment for covariates. African Americans tended to have similar but stronger patterns of association between circulating leukocytes and CKD incidence than whites, although the differences between race groups were not statistically significant. We also found that eGFR and BP were higher at each visit in African Americans than whites between ages 45 and 65. These findings support a potential role for circulating specific leukocytes in the pathogenesis of kidney dysfunction, especially in African Americans, indicating the leukocyte-related renal mechanism of essential hypertension (HT). PMID- 22054784 TI - Low-temperature osmotic dehydration improves the quality of intermediate moisture meats. AB - Dehydration of meat at low temperature (4 degrees C) with a new dehydrating sheet to obtain intermediate moisture meat produced more desirable results than did more rapid dehydration at 25 degrees C, because the native state of meat proteins was better retained at the lower temperature. At low temperature with replacement of the dehydrating sheet once per day, the water content decreased to 57% after 150 h. Water activity (a(w)) dropped to 0.965. Myofibrils could be prepared readily from meat after 150 h at 4 degrees C, and the myofibrils were induced to contract by addition of Mg(2+)-ATP solution and therefore retained biological activity. Electron microscopic observation showed that intermediate moisture meat prepared at 4 degrees C retained the original muscle structure to a large extent. Myosin could be extracted easily from intermediate moisture meat dehydrated at 4 degrees C after 10 days of storage at 25 degrees C. No marked difference in the effect of dehydration on muscle was observed among species (beef, pork, chicken and rabbit). Results show that dehydration at low temperature (4 degrees C) with use of the new dehydrating sheet enables intermediate moisture meat of good quality to be manufactured. PMID- 22054785 TI - Solubilisation of bovine rumen and decolorisation of bovine blood by enzymic hydrolysis with alcalase. AB - Enzymic hydrolysis has potential for upgrading a range of waste materials from the meat industry. The effects of the reaction variables pH, time, temperature, enzyme concentration and rumen concentration on the solubilisation of rumen by Alcalase have been determined. Reaction progress curves showed rapid initial rates followed by a gradual decline in rate. The optimum reaction pH was 8.5. Optimum reaction temperatures for hydrolysis and solubilisation were about 55 degrees C and 60 degrees C, respectively, for a 3-h reaction. Solubilisation and degree of hydrolysis both increased with increasing enzyme concentration and decreased with increasing substrate concentration. PMID- 22054786 TI - Studies of extra low voltage electrical stimulation of mature beef carcasses. AB - The quality characteristics of biceps femoris (BF) and semimembranosus (SM) roasts obtained from mature cow carcasses treated with a commercial extra low voltage (30 V) electrical stimulation (LVES) system were determined. LVES was applied for either 2 (ESII) or 4 min (ESIII). Evaluations were conducted on meat obtained from control sides (no ES) aged for either 48 h (Ia) or 7 days (Ib) and from ES sides aged 48 h. ES caused a reduction (P<0.001) in pH values at 2 and 6 h post mortem. At 24 h, the pH of muscles from all carcasses was about 5.5. ES duration did not influence muscle pH. Rib-eye muscle colour for ESII and ESIII carcasses was lighter and brighter (P<0.05) than that of control carcasses. Generally stimulated BF roasts had greater cooking losses than control Group Ib roasts; SM roasts from ES carcasses had lower losses than comparable to Group Ib roasts. ES duration had no effect on per cent cooking losses. Trained panelists generally detected few significant effects in BF roasts due to ES. Warner Bratzler data indicated that ESII and ESIII BF roasts were similar and significantly more tender than comparable control Group Ib samples: OTMS data indicated that all BF roasts were similar in tenderness. However, SM roasts from ES carcasses were judged more soft (Groups II and III) and tender (ESII) than comparable control roasts. Instrumental measurements of tenderness for SM roasts tended to support the taste panel results. Generally, duration of LVES had no effect on the eating quality of either BF or SM roasts. Since LVES effects on the palatability of SM roasts were evident but the effects of stimulation of BF roasts were few, further studies of this LVES system are needed before its use can be recommended. Generally, increasing post-mortem ageing time for mature control carcasses did not influence either BF or SM roast quality. PMID- 22054787 TI - The effect of DFD classification and internal cooking temperature on certain pork muscle characteristics. AB - The data incorporated in this experiment were gathered from 14 littermate pairs of swine of the same sex differing in weight by <4.5 kg with one animal in each pair subjected to standardized stress. Samples of the Longissimus dorsi (LD) and the Psoas major (PM) muscles were cooked to internal temperatures of 64, 70 and 76 degrees C. The samples of the Quadriceps femoris (QF) muscle were cooked to internal temperatures of 70 and 76 degrees C. DFD classification of the raw muscle was determined by the 48 h pH. Stress produced DFD meat in the PM and QF muscles but not in the LD muscle. DFD muscle required shorter time to reach any of the cooked internal temperatures studied when compared to normal muscle. Slightly-DFD PM muscle more closely resembled the normal muscle in all variables except the panel tenderness score. Cooking DFD PM muscle to an internal temperature 6 degrees C higher than normal muscle caused a reverse in the direction of cooking loss, fiber diameter, tenderness and expressible water when compared to normal and DFD muscle cooked to the same internal temperature. Cooking DFD PM muscle to an internal temperature 12 degrees C higher than normal muscle produced changes associated with increasing the internal temperature of normal muscle. Similar trends, as described for the PM muscle, were observed in the QF muscle. PMID- 22054788 TI - A comparison between tensile and shear adhesive strength of meat-myosin junctions. AB - A model meat-myosin gel junction was used to compare the adhesive strength of binding junctions when subject to tensile or shear forces. This comparison was made on junctions cooked to 80 degrees C with three different alignments of muscle fibres with respect to the junction plane. Tensile adhesive strength (TAS) and shear adhesive strength (SAS) did not differ significantly when fibres in both of the bound pieces of meat were perpendicular to the plane of the myosin gel function (90 degrees /90 degrees junction). However, SAS was higher than TAS if the muscle fibres in one or both of the meat pieces were parallel to the plane of the junction. This suggests that tensile failure of binding junctions is the more likely mode of failure. Differences between SAS and TAS in any one junction orientation were small compared to the effect of muscle fibre orientation with respect to the junction; both TAS and SAS were highest for 90 degrees /90 degrees junctions and lowest when muscle fibres in both meat pieces were parallel to the junction (0 degrees /0 degrees junctions). PMID- 22054789 TI - Water activity: Theory and applications to food (IFT Basic Symposium Series). Edited by Louis B. Rockland and Larry R. Beuchat. 1987. 424 pp., bound, illustrated. Price: $59.75 (US and Canada); $71.50 (All other countries). (Prices subject to change without notice). PMID- 22054790 TI - Effect of breed and nutrition on the productive traits of beef cattle in south east Brazil: Part 3-Meat quality. AB - Significant differences in a number of economically important appearance and palatability traits were recorded between the Bos indicus and Bos taurus breeds. Muscles from the Charolais and Canchim animals were consistently and significantly lighter in colour than those from the zebu breeds, even after pH effects had been taken into account. Differences were shown to be directly related to variations in muscle myoglobin levels, but may have been complicated by observed textural differences. Muscles from the zebu animals were not noticeably coarser grained, having significantly larger fibre diameters and fibre bundle sizes. The inferiority of the Bos indicus breeds in terms of muscle tenderness was clearly demonstrated. Significantly higher shear force values were recorded in all muscles from the Nelore and Guzera breeds, except the Psoas major. These differences were also detected by taste panel evaluation. Major differences between breeds were demonstrated in the thermo-stability of extracted intra-muscular connective tissue elements, being highest in the zebu breeds, intermediate in the Canchim and lowest in the Charolais. These solubility characteristics were thought to be due to differences in the relative proportions of genetically different collagen types in the muscles and an association between coarseness of texture and toughness was shown. PMID- 22054791 TI - Singular and combined effects of electrical stimulation, post-mortem ageing and blade tenderisation on the palatability attributes of beef from young bulls. AB - Thirty Santa Gertrudis bulls (approximately 15-18 months old) were slaughtered, dressed and split into siides. The right side of each carcass was electrically stimulated (ES) with seventeen impulses (1.8s impulse duration; 1.8s interval between impulses) of 550 V (AC) and 5 A while the left side served as a non stimulated control (not-ES). At 24h post morten, USDA quality and yield grade data were obtained from each side. On the second day post mortem, all sides were fabricated and strip loins, top sirloin butts and ribeyes were obtained from each side for post-mortem ageing and blade tenderisation studies. Steaks were removed after a post-mortem ageing period of 4 or 18 days and before (not-BT) or after blade tenderisation (BT) for sensory panel evaluations or shear force determinations. ES sides had more youthful lean maturity (P < 0.0001), higher marbling (P < 0..002), higher USDA quality grades (P < 0.0.0001) and finer textured lean (P < 0.002) than did not-stimulated (not-ES) sides. ES significantly improved (P < 0.05) palatability traits in two of twenty-four comparisons; BT significantly improved palatability traits in twelve of twenty four comparisons and 18-day post-mortem ageing significantly improved palatability traits in seven of twelve comparisons. No significant reductions (P < 0.05) in shear force values were observed for steaks from ES versus not-ES sides while significant reductions (P < 0.05) were observed for steaks from BT versus non-BT cuts (four of six comparisons) and for steaks from cuts aged for 18 versus 4 days (ten of twelve comparisons). BT and 18-day post-mortem ageing were more effective for increasing palatability or for decreasing shear force requirements than was ES; however, ES greatly improved lean colour of meat from bulls. PMID- 22054792 TI - Effect of oxygen and storage temperature on intermediate moisture meat products. AB - During storage of glycerol desorbed intermediate moisture meats at 38 degrees C it was found that, for both protein crosslinking and loss of haemoprotein character to occur, oxygen must be present. However, collagen degradation, as monitored by the formation of water-soluble hydroxyproline containing fragments, still occurred in the absence of oxygen although the rate of degradation was slower than that observed in aerobically stored samples. The rates of the various deteriorative reactions also varied with storage temperature, there being the expected decrease in rate with temperature for both the crosslinking and haemoprotein breakdown reactions. However, the temperature dependence of the collagen breakdown reaction was apparently more complex as there was no measurable breakdown, even during several months of storage, at temperatures of 17 degrees C and below. PMID- 22054793 TI - Electrical stunning of sheep. AB - In seventy Texel breed sheep with a live weight of about 43 kg electrocorticogram (ECoG) electrodes were implanted in the dura mater. The day after the operation the sheep were electrically stunned with scissor model tongs on the head. Various currents and voltages were used. A current strength of 0.33 A was statistically estimated to stun 90% of the sheep effectively, which means an immediate induction of a general epileptiform insult. The duration of an insult, using 600 V, is significantly longer than using 300 V, although the shortest duration was 23 s and 22 s, respectively. In all instances a paroxysmal ventricular tachycardia was observed after stunning. In the interests of animal welfare, electrical stunning of sheep should be performed with an amperage of at least 0.5 A (160 V) and throat cutting should take place within 16 s. PMID- 22054794 TI - Heat-induced tenderisation of meat by endogenous carboxyl proteases. AB - The role of carboxyl proteases in tenderising meat was investigated by injecting the inhibitors, pepstatin and EPNP, into pre-rigor muscle. The increase in shear force values induced by these inhibitors provided a minimum estimate of the extent to which endogenous carboxyl proteases normally tenderise meat at 60 degrees C. Gel electrophoresis showed that connectin was hydrolysed to a greater extent than other muscle proteins at this temperature and that breakdown of connectin was inhibited by pepstatin and EPNP. Thus it is likely that, when intact, connectin may contribute to the strength of cooked meat. PMID- 22054795 TI - Macroscopic wrinkling of muscle fibres, a source of error in objective assessment of meat toughness. AB - Post-rigor shortening of muscle resulting in macroscopic fibre wrinkling was studied in muscle samples which entered rigor restrained in a stretched condition and were subsequently freed. The amount of wrinkling varied with the initial degree of stretch pre rigor and with the muscle treatment post rigor, depending on such variables as (1) whether or not the muscle was heated and (2) if heated, at what stage the restraint was removed. The consequences of fibre wrinkling relative to the objective testing of meat toughness are discussed. PMID- 22054796 TI - Electrical stimulation of ante-mortem stressed beef. AB - Ten heifers were stressed before slaughter and one side of each animal was electrically stimulated. Six of the ten animals produced dark-cutting beef on the non-stimulated side. Electrical stimulation had no effect on muscle colour, ultimate pH, shear force or any of the sensory characteristics of muscle fibre tenderness, overall tenderness, connective tissue amount, juiciness, flavour desirability or overall palatability. The data from this study indicate that rapid pH decline is necessary for electrical stimulation to produce its desired effects and that neither the process of stimulation itself nor the contractions produced can cause improved quality of electrically stimulated beef if attendant changes in muscle pH do not occur. PMID- 22054797 TI - Extended-release quetiapine as monotherapy for the treatment of adults with acute mania: a randomized, double-blind, 3-week trial. AB - BACKGROUND: Bipolar disorder, a highly recurrent and chronic condition, often necessitates periods of hospitalization and requires lifelong treatment with medication. It is characterized by alternating episodes of mania and depression. Given the severity of mania, physicians must be able to control symptoms rapidly. OBJECTIVE: The purpose of this pivotal, Phase III trial was to evaluate the efficacy and tolerability of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy in improving manic symptoms in patients with bipolar I disorder. METHODS: This was a 3-week, randomized, parallel-group, double-blind, placebo-controlled study. Patients aged 18 to 65 years with bipolar I disorder (most recent episode manic or mixed; with or without rapid cycling) were randomized to receive placebo or quetiapine XR monotherapy once daily (300 mg on day 1; 600 mg on day 2; flexible dosing, 400-800 mg, from day 3 through day 22 [study end point, week 3]). The primary outcome measure was the change from baseline to study end in the Young Mania Rating Scale (YMRS) total score. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale (MADRS) total score, YMRS response (>=50% reduction in YMRS) and remission (YMRS score <=12 at final visit) rates, and change from baseline to week 3 in Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S) and CGI-BP-Change (CGI BP-C) scores. Safety profile and tolerability evaluations included monitoring of adverse events, clinical laboratory values, vital signs, extrapyramidal symptoms (including akathisia), and electrocardiogram results. RESULTS: Compared with placebo (n = 159), quetiapine XR monotherapy (n = 149; mean daily dose, 604 mg) significantly improved manic symptoms starting at day 4 (first assessment; P < 0.001), with sustained improvement to study end (week 3; P < 0.001). MADRS scores showed greater improvement from baseline to study end with quetiapine XR than with placebo (P = 0.004). Response and remission rates were significantly greater (P < 0.01) with quetiapine XR than with placebo at study end. Quetiapine XR also resulted in significant improvements over placebo in CGI-BP-S and CGI-BP-C scores (P < 0.001 and P < 0.001, respectively). Adverse events were mild to moderate in intensity; the most common ones associated with quetiapine XR were sedation, dry mouth, and somnolence. CONCLUSION: This 3-week trial suggests that quetiapine XR (400-800 mg) once-daily monotherapy is efficacious (from day 4) and generally well tolerated in patients with manic or mixed episodes of bipolar I disorder. PMID- 22054798 TI - Is water diffusion isotropic in the cirrhotic liver? a study with diffusion weighted imaging at 3.0 Tesla. AB - RATIONALE AND OBJECTIVES: Water molecule motion has been shown to be isotropic in healthy liver as assessed by diffusion-weighted imaging (DWI). The purpose of this study was to investigate whether this assumption is still valid in the cirrhotic liver. MATERIALS AND METHODS: Twelve cirrhotic patients and 12 controls underwent DWI on a 3.0T-system. We used an echo-planar sequence independently applying unidirectional motion-probing gradients along read-(x), phase-(y), and slice-(z) directions, respectively. Liver apparent diffusion coefficient (ADC) and perfusion fraction (f) were calculated along each gradient direction, based on two b-values sets (0-400 and 0-800 seconds/mm(2)). Measurement was repeated at two different axial slices of the liver. RESULTS: No significant difference among x, y, and z- ADC (and f) of the liver was found within controls and cirrhotic patients (P > .01), regardless of the set of b-values or the slice of measurement. ADC was lower in cirrhotic patients than in controls (difference of 0.24-0.39 * 10(-3) mm(2)/seconds at b = 800 seconds/mm(2); P = .000-.0139). Perfusion fraction f was lower in cirrhotics than in controls, irrespective of the b-values set or the slice of measurement (difference of 0.05-0.15; P < .0001 .0885). CONCLUSION: The liver shows isotropic water diffusion in cirrhotics, despite fibrotic distortion leading to decreased ADC as compared to controls. Our results emphasize that the correlation between parenchymal changes in liver fibrosis and the ADC estimate remains an elusive goal based on the state-of-the art DWI technique. PMID- 22054799 TI - Impact of ultra-early coiling on clinical outcome after aneurysmal subarachnoid hemorrhage in elderly patients. AB - RATIONALE AND OBJECTIVES: The incidence of aneurysmal subarachnoid hemorrhage is increasing in the elderly as life expectancy increases. The purpose of this study was to analyze whether ultra-early coiling of ruptured intracranial aneurysms improves clinical outcomes in elderly patients. MATERIALS AND METHODS: Records of patients (aged >= 70 years) with aneurysmal subarachnoid hemorrhage treated with endovascular coiling were retrieved. Patients were classified into two groups: group A (patients coiled within 24 hours of subarachnoid hemorrhage) and group B (patients coiled >=24 hours after subarachnoid hemorrhage). For each group, patient demographics, World Federation of Neurological Surgeons clinical grade, Fisher computed tomographic grade, aneurysm characteristics, and clinical outcomes were recorded. Outcomes were measured using the Modified Rankin Scale at 6 months. RESULTS: Fifty-six patients were coiled within 24 hours of subarachnoid hemorrhage (group A) and 40 patients at >=24 hours after subarachnoid hemorrhage (group B). Groups A and B had similar clinical and angiographic characteristics. Clinical outcomes showed that a total of 87.5% of patient (49 of 56) in group A were independent (Modified Rankin Scale score 0-2) compared with 70.0% of patients (28 of 40) in group B (P = .034). In multivariate logistic regression analysis, ultra-early coiling (odds ratio, 3.860; 95% confidence interval, 1.125 13.249; P = .032) proved to be an independent predictor of better clinical outcome (Modified Rankin Scale score 0-2). CONCLUSIONS: Ultra-early (<24 hours after subarachnoid hemorrhage) coiling of ruptured aneurysms was marginally associated with improved clinical outcomes compared to coiling at >=24 hours in elderly patients. Larger, prospective studies are required to adequately assess outcome differences between these two groups. PMID- 22054800 TI - Low-grade bone lesions in survivors of childhood medulloblastoma/primitive neuroectodermal tumor. AB - OBJECTIVES AND RATIONALE: Medulloblastoma/primitive neuroectodermal tumor (MB/PNET) is the most common malignant tumor of the central nervous system (CNS) in children. MB/PNET survivors are at an increased risk for developing second malignancies. Little has been reported on development of low-grade lesions of the calvarium in the radiation field in MB/PNET survivors. The purpose of this study was to assess the frequency of the low-grade bone lesion development in the radiotherapy field in pediatric MB/PNET survivors and describe the imaging characteristics of these lesions. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective review which was compliant with Health Insurance Portability and Accountability Act. Forty-one MB/PNET patients (29 male) who survived for at least 2 years after initiation of radiation therapy were included. The medical records were reviewed. The most recent available brain magnetic resonance imaging studies were evaluated. RESULTS: Three patients (7.3%) developed low-grade calvarial lesions and underwent resection and/or biopsy of the lesions. There were one Langerhans cell histiocytosis, one benign spindle cell lesion with myxoid change, and one fibrous dysplasia. CONCLUSION: Development of low-grade bone lesions of calvarium is not very rare in pediatric PNET/MB survivors. Bones in the radiation therapy field need to be carefully examined for assessment of secondary lesions. PMID- 22054801 TI - MDCT necrosis quantification in the assessment of hepatocellular carcinoma response to yttrium 90 radioembolization therapy: comparison of two-dimensional and volumetric techniques. AB - RATIONALE AND OBJECTIVES: The purpose of this study is to evaluate the reproducibility and agreement of tumor necrosis quantification performed by two dimensional and volumetric methods in a cohort of patients with hepatocellular carcinoma (HCC) treated with yttrium-90 ((90)Y) radioembolization. MATERIALS AND METHODS: Twenty-nine consecutive patients (21 men, 8 women; mean age 66.6 years; age range, 44-90 years) with HCC treated with (90)Y radioembolization that underwent liver multidetector computed tomography (MDCT) were included. Two independent radiologists evaluated the necrosis proportion of the lesions with two-dimensional (2D) measurements according to the European Association for the Study of the Liver guidelines, and with a volumetric method using a voxel-by voxel analysis. Interobserver reproducibility for each method was assessed by using within-subject coefficients of variation (WSCV), intraclass correlation coefficients (ICC), and Lin's concordance correlation coefficients (LCC). Agreement between both methods was assessed by using the Bland-Altman plot and the paired t-test. RESULTS: The volumetric method was more reproducible (WSCV = 27.8%; ICC = 0.914; LCC = 0.909) than the 2D (WSCV = 43.8%; ICC = 0.723; LCC = 0.841). There was a significant difference in the mean calculated necrosis proportions based on 2D and volumetric methods (P = .0129). CONCLUSION: Voxel-by voxel quantification of HCC necrosis is a more reproducible method than 2D analysis. PMID- 22054802 TI - Partnering with Engineers to Identify and Empirically Evaluate Delays in Magnetic Resonance Imaging Laying the Foundations for Quality Improvement and System-based Practice in Radiology. AB - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the feasibility of partnering with engineering students and critically examining the merit of the problem identification and analyses students generated in identifying sources impeding effective turnaround in a large university department of diagnostic radiology. Turnaround involves the time and activities beginning when a patient enters the magnetic resonance scanner room until the patient leaves, minus the time the scanner is conducting the protocol. MATERIALS AND METHODS: A prospective observational study was conducted, in which four senior undergraduate industrial and operations engineering students interviewed magnetic resonance staff members and observed all shifts. On the basis of 150 hours of observation, the engineering students identified 11 process steps (eg, changing coils). They charted machine use for all shifts, providing a breakdown of turnaround time between appropriate process and non-value-added time. To evaluate the processes occurring in the scanning room, the students used a work-sampling schedule in which a beeper sounded 2.5 times per hour, signaling the technologist to identify which of 11 process steps was occurring. This generated 2147 random observations over a 3-week period. RESULTS: The breakdown of machine use over 105 individual studies showed that non-value-added time accounted for 62% of turnaround time. Analysis of 2147 random samples of work showed that scanners were empty and waiting for patients 15% of the total time. Analyses showed that poor communication delayed the arrival of patients and that no one had responsibility for communicating when scanning was done. CONCLUSIONS: Engineering students used rigorous study design and sampling methods to conduct interviews and observations. This led to data-driven definition of problems and potential solutions to guide systems-based improvement. PMID- 22054803 TI - Selection of arterial input function for postprocessing of cerebral ct perfusion in chronic unilateral high-grade stenosis or occlusion of the carotid or middle cerebral artery. AB - RATIONALE AND OBJECTIVES: We evaluated the effect of the arterial input function (AIF) on computed tomography perfusion (CTP) in patients with unilateral high grade stenosis or occlusion in the carotid artery or middle cerebral artery without acute stroke. MATERIALS AND METHODS: CTP datasets were retrospectively postprocessed using the same venous output function and different AIF selections: the second segment of the anterior cerebral artery (A2 AIF), the second segment of the middle cerebral artery (MCA) on the lesion side (affected M2 AIF), and M2 on the contralateral side (nonaffected M2 AIF). We measured CTP values in the region of interest (ROI) in the bilateral MCA territory and evaluated the lesion to-contralateral ratios. RESULTS: The mean and standard deviations of cerebral blood flow (CBF) on the normal side were similar to previously reported data only when using "non-affected M2 AIF." Selecting an "affected M2 AIF" overestimated the CBF and shortened the mean transit time (MTT) in normal and lesion areas. Selecting an "A2 AIF" may cause overestimation of CBF in the normal side in patients with nonaffected-side A1 hypoplasia or occlusion. The sensitivity of the CBF ratio or MTT ratio to detect these unilateral cerebrovascular diseases was 100% using "nonaffected M2 AIF for bilateral MCA ROIs" and 70% (CBF ratio) and 90% (MTT ratio) using "respective AIF." CONCLUSION: The use of "nonaffected AIF for the bilateral MCA ROIs" was found to be the best of these AIF-ROI combinations in patients with chronic unilateral carotid or M1 severe stenosis or occlusion. PMID- 22054804 TI - Breast cancer risk assessment in 64,659 women at a single high-volume mammography clinic. AB - RATIONALE AND OBJECTIVES: In 2007, the American Cancer Society (ACS) recommended that women at elevated risk of breast cancer be screened with breast magnetic resonance imaging (MRI) as an adjunct to mammography. This study estimates the proportion of women presenting for screening mammography who are at elevated lifetime risk of breast cancer as determined by the Gail model. This study provides preliminary information for a proposed follow-up study, including the proportion of women who completed the recommended MRI at the same clinic that had conducted the risk assessment. MATERIALS AND METHODS: This study is an observational prospective cohort of 64,659 women presenting for mammographic screening at a single high-volume clinic. If a woman reported a first-degree maternal relative with breast cancer and had at least 20% lifetime risk on the Gail model, the radiologist's report included a recommendation that the primary care physician refer the woman for breast MRI screening. Records were examined to determine if women completed the recommended MRI at the clinic within one year of the initial risk assessment. RESULTS: Of 64,659 women, 1,246 (1.9%) had a lifetime risk of breast cancer of 20% or greater, and 436 (0.7 %) had a lifetime risk of breast cancer 25% or greater. Of the women at elevated risk, 173 (13.9%) completed the recommended breast MRI screening at the clinic within a year. CONCLUSION: The effectiveness of matching screening intensity to risk on cancer detection, biopsy rate, and cost should be evaluated by studying multiple clinics and multiple risk assessment tools. PMID- 22054805 TI - Left atrial volume: comparison of 2D and 3D transthoracic echocardiography with ECG-gated CT angiography. AB - RATIONALE AND OBJECTIVES: Left atrial volume (LAV) measurement by conventional two-dimensional (2D) transthoracic echocardiography (TTE) may be limited by the geometric model, by suboptimal definition of left atrial endocardium, or by chamber foreshortening. Three-dimensional (3D) TTE is posited to eliminate chamber foreshortening, and LAV measurement by 3D TTE should be more reflective of true LAV. The aim of this study was to compare conventional 2D TTE and newer 3D TTE for measurements of LAV to multidetector computed tomographic (MDCT) measurements using automated chamber reconstruction (ACR). MATERIALS AND METHODS: Twenty-two subjects consented to undergo 2D TTE and 3D TTE immediately prior to or following coronary computed tomographic angiography. LAV was calculated from 2D TTE using the area-length method (ALM) and from 3D TTE with the ALM as well as with a 3D model. Electrocardiographically gated coronary computed tomographic angiography was performed in helical mode. LAV was measured using the ALM as well as ACR. RESULTS: LAV was significantly smaller by 2D TTE (80 +/- 21 mL) and 3D TTE (90 +/- 24 mL with the ALM, 61 +/- 16 mL with the 3D model) compared to MDCT ACR (120 +/- 30 mL) (P < .01). Correlation between MDCT ALM and MDCT ACR was excellent (mean Delta = -1.4 +/- 14 mL, r = 0.91). Correlation with MDCT ACR was no better for 3D TTE (r = 0.80) than for 2D TTE (r = 0.80). CONCLUSIONS: LAV is underestimated by both 2D TTE and 3D TTE relative to coronary computed tomographic angiography. Excellent agreement between the ALM and ACR with MDCT imaging suggests that the geometric model plays a negligible role in the underestimation of LAV. Underestimation of LAV by echocardiography is likely related to suboptimal definition of left atrial contour. PMID- 22054806 TI - Effect of scan time on perfusion and flow extraction product (K-trans) measurements in lung cancer using low-dose volume perfusion CT (VPCT). AB - RATIONALE AND OBJECTIVES: To assess the effect of measurement time on blood flow (BF), blood volume (BV), and k-trans-values (flow extraction product) in patients undergoing volume perfusion computed tomography (VPCT) for lung cancer. MATERIALS AND METHODS: This prospective study was approved by our local Research Ethics Committee and informed consent was obtained in all patients. Between December 2009 and December 2010, 75 VPCT scans were obtained in 54 consecutive patients (15 women, 39 men) with histologically confirmed lung cancer. A 64-second VPCT of the tumor (80 kV, 60 mAs) using 128 * 0.6-mm collimation, 6.9-cm z-axis coverage and a total of 26 volume measurements, was performed. BF, BV, and K(trans) were determined. Data evaluation was performed for different measurement times (64 seconds, 45 seconds, 39 seconds, and 36 seconds) by removing the last two, four, and five scans and repeating the analysis. A one-way repeated-measures analysis of variance was used to test for effects of measurement time on BF, BV, and k trans and unpaired/paired Student t-tests were applied for comparisons within/between groups, respectively. RESULTS: No effect of measurement time on BF values was noted (P > .05), whereas a significant decrease of BV values (at 39 seconds: 71% +/- 2% of 64-second values) and a significant increase of k-trans values (at 39 seconds: 146% +/- 8% of 64-second values) were observed with progressively shortened measurement time (P < .05, respectively). Additionally, with reduced measurement time, the increase in k-trans-values was significantly more pronounced in those patient groups with higher BV (at 39 seconds: 171% +/- 15% versus 120% +/- 3% of 64-second measurements), and those with lower k-trans (at 39 seconds: 167% +/- 16% versus 126% +/- 4% of 64-second measurements) (P < .05, respectively). CONCLUSION: Whereas estimation of BF in lung cancer was independent from VPCT measurement time within the chosen ranges, approximation of both BV and k-trans was affected by measurement duration. A fixed measurement time of 40 seconds is recommended. PMID- 22054807 TI - The influence of blood supply on high intensity focused ultrasound a preliminary study on rabbit hepatic VX2 tumors of different ages. AB - RATIONALE AND OBJECTIVES: The aim of this study was to explore the effects of blood supply on high-intensity focused ultrasound (HIFU) applied to rabbit hepatic VX2 tumors of different ages. MATERIALS AND METHODS: Eighteen rabbits with VX2 hepatic tumors were randomly divided into three groups according to the time of sacrifice after tumor implantation: 10, 15, or 20 days. Contrast-enhanced ultrasound was performed immediately before HIFU ablation. The same settings for HIFU dose parameters were used to ablate the central tumor area in each group, and the real-time temperature of the targeted site of the tumor was measured. After HIFU, the coagulation necrosis volumes of tumor tissue and the microvascular density of residual tumor tissue were determined. RESULTS: Histopathologic analysis showed that the extent of a tumor's blood supply followed the order 10-day group > 15-day group > 20-day group (P < .01). Contrast enhanced ultrasound showed the same results. There was no statistically significant difference among the three groups in terms of temperature-increase parameters during HIFU treatment (P > .05). However, there were statistically significant differences between the groups in terms of temperature-decrease parameters during HIFU treatment and in terms of necrosis volumes after HIFU treatment (P < .05). Necrosis volume was inversely related to absolute enhanced intensity (r = -0.823, P < .001). CONCLUSIONS: The extent of a tumor's blood supply had a significant effect on the temperature-decrease phase but not on the temperature-increase phase during HIFU treatment. The longer the temperature decrease phase, the more slowly heat dissipated after HIFU, resulting in larger coagulation necrosis volumes. PMID- 22054808 TI - [Quadricuspid aortic valve--10-year case series and literature review]. AB - INTRODUCTION: Quadricuspid aortic valve is a rare malformation, with an estimated incidence of 0.003 to 0.043% of all congenital heart disease. It usually appears as an isolated congenital anomaly, but may also be associated with other malformations, the most common being coronary artery anomalies. Current technology enables noninvasive diagnosis in most cases. This entity's natural history is progression to valve regurgitation, which is rare before adulthood. OBJECTIVE: Case review of quadricuspid aortic valve patients diagnosed in the last 10 years in a tertiary pediatric cardiology center. METHODS: Retrospective chart review of patients diagnosed with quadricuspid aortic valve between January 2000 and December 2009. RESULTS: Over the past 10 years, four cases of quadricuspid aortic valve were diagnosed in children aged between 6 months and 8 years, two male. In three cases, the four leaflets were of similar size, which is the most common finding. Two of the valves functioned normally and two had minimal regurgitation. All patients had associated cardiac malformations (one atrial and two ventricular septal defects, one supravalvular aortic stenosis and one quadricuspid pulmonary valve). One patient was also diagnosed with Williams syndrome. During a median follow-up of 2 years (0-9), all patients remained asymptomatic and none required medical or surgical treatment of the aortic valve. CONCLUSION: Diagnosis of quadricuspid aortic valve is rare, especially in children, since most patients are asymptomatic and have normally functioning valves. In this study, half the patients had minimal aortic regurgitation. Contrary to what is described in the literature, all patients had concomitant cardiac malformations. We provide the first description of this entity's association with Williams syndrome. Clinical follow-up should be maintained in these patients in order to promptly detect the onset or worsening of functional alterations and to enable appropriate therapeutic intervention. PMID- 22054809 TI - [Primary care physicians forum]. PMID- 22054810 TI - Eltrombopag: an oral thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura. AB - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is a relatively rare acquired autoimmune disease characterized by either decreased platelet production or increased platelet destruction leading to reduced platelet counts and increased risk of bleeding. Immune modulators have been used in treatment; however, a novel class of thrombopoietin mimetics has recently been developed. Eltrombopag is approved for patients with chronic ITP who have failed initial treatments with traditional immune modulators or splenectomy. OBJECTIVES: The goals of this review were to summarize the pharmacology, pharmacokinetic properties, efficacy, and tolerability of eltrombopag and review the approved and investigational uses of this drug. METHODS: A search of Cochrane Central Register of Clinical Trials and clinicaltrials.gov was conducted using the terms eltrombopag or SB-497115-GR. In addition, all reviews and preclinical and clinical studies published in English between January 1980 and January 2011 were identified in PubMed and Cochrane Database of Systemic Reviews using the same terms. RESULTS: A total of 153 publications and 13 clinical trials were identified; 14 publications were excluded because they were not published in English. A Phase III trial randomized 114 patients with ITP 2:1 to eltrombopag 50 mg or placebo and demonstrated by day 43 a significantly greater proportion of patients responding in the eltrombopag group than in the placebo group (59% vs 16%, odds ratio [OR] = 9.61; 95% CI, 3.31-27.86; P < 0.0001). The mean percentage change of platelets from baseline in the eltrombopag group was double that of the placebo group at day 8 and was sustained several-fold higher throughout the remainder of the treatment period. Another Phase III trial evaluated the efficacy and safety of eltrombopag compared with placebo over 6 months. The odds of responding (defined as a platelet count of 50-400 * 10(9)/L) were 8 times higher in patients receiving eltrombopag than in those in the placebo group (95% CI, 3.59-18.73; P < 0.0001). Bone marrow fibrosis and hepatotoxicity are the most serious adverse effects, and nausea and vomiting are the most common. Eltrombopag is also being evaluated in the treatment of thrombocytopenia secondary to hepatitis C infection, chemotherapy, acute leukemia, and myelodysplasias. CONCLUSION: Eltrombopag is well tolerated and effective in raising platelet counts in patients with chronic ITP. PMID- 22054812 TI - [Salmonella glenohumeral arthritis]. AB - We report the first case of glenohumeral Salmonella arthritis in an immunocompetent 86-year-old woman. There was no entry point. An empirical antibiotherapy was started then adapted according to culture results. Given the persistence of symptoms, an arthroscopy was performed at 72 hours for a joint lavage and synovectomy. Postoperative course was good. Apyrexia was obtained by 72 hours and inflammatory syndrome was normalized in 12 days. The patient was reviewed regularly until the 3rd month. She has no clinical sequelae. Her osteoarthritis remained stable throughout follow-up. PMID- 22054813 TI - [Large diameter nerve conduits use in the upper limb: report of four cases and literature review]. AB - Defects of the median, ulnar or radial nerves in the forearm, can be treated by conventional nerve grafts, or by interposing a synthetic guide such as nerve conduits. Wounds without nerve loss treated with simple suture may be supplemented by sleeving to prevent the nerve irritation symptoms using a nerve conduit or a vein sleeve. We studied the results of nerve conduits in both cases in a single-center retrospective study. PATIENTS AND METHODS: Four patients underwent surgery with placement of a nerve conduit in the forearm, between May 2007 and January 2011. All patients were reviewed by the same examiner. Pain, tenderness, motor (Medical Research Council classification, MRC), time to return to work and self-evaluation by the patient were measured. The averages of these data were calculated and compared with results of other studies in the literature, the nerve grafts for defects and the Socket joints for venous ulcers. RESULTS: The decrease is on average 30 months (2 years). The defect never exceeds 40mm and is 22mm on average. According to the classification MRC, sensitivity found after inserting nerve conduits in the forearm after a defect is excellent (S4) for two of three patients and good (S3) for the third. Motor results were very good (M4 and M3 for one patient) andM2 for the other. As for the insertion of a nerve conduit as a sleeve, the result is good in terms of sensitivity (S3) and excellent in terms of motor (M5) for our case in the study. For our small group of patients with neuroma we obtained, results similar to those published in the literature with conventional techniques. CONCLUSION: The nerve conduits seem to give results similar to conventional techniques, in situations of defects or neuromasin the forearm, with a diameter greater than 2mm, but defects of less than 30mm. PMID- 22054815 TI - A joint encryption/watermarking algorithm for verifying the reliability of medical images: application to echographic images. AB - In this paper we propose a joint encryption/watermarking algorithm for the purpose of protecting medical images. The proposed solution gives access to the outcomes of the image integrity and of its origins as its attachment to one patient even if the image is stored encrypted. In this study, the given solution combines the RC4 stream cipher and two substitutive watermarking modulations: the Least Significant Bit Method and the Quantization Index Modulation. If watermarking and encryption are conducted jointly at the protection stage, watermark extraction and decryption can be applied independently. Experimental results achieved on 8 bits encoded echographic images illustrate the overall performances of the proposed scheme. At least, a capacity rate of 1 and 0.5 bits of message per pixel of image can be embedded in the spatial and the encrypted domains respectively, with a peak signal to noise ratio greater than 49 dB. PMID- 22054814 TI - Intracellular recording in behaving animals. AB - Electrophysiological recordings from behaving animals provide an unparalleled view into the functional role of individual neurons. Intracellular approaches can be especially revealing as they provide information about a neuron's inputs and intrinsic cellular properties, which together determine its spiking output. Recent technical developments have made intracellular recording possible during an ever-increasing range of behaviors in both head-fixed and freely moving animals. These recordings have yielded fundamental insights into the cellular and circuit mechanisms underlying neural activity during natural behaviors in such areas as sensory perception, motor sequence generation, and spatial navigation, forging a direct link between cellular and systems neuroscience. PMID- 22054816 TI - ThyroScreen system: high resolution ultrasound thyroid image characterization into benign and malignant classes using novel combination of texture and discrete wavelet transform. AB - Using right equipment and well trained personnel, ultrasound of the neck can detect a large number of non-palpable thyroid nodules. However, this technique often suffers from subjective interpretations and poor accuracy in the differential diagnosis of malignant and benign thyroid lesions. Therefore, we developed an automated identification system based on knowledge representation techniques for characterizing the intra-nodular vascularization of thyroid lesions. Twenty nodules (10 benign and 10 malignant), taken from 3-D high resolution ultrasound (HRUS) images were used for this work. Malignancy was confirmed using fine needle aspiration biopsy and subsequent histological studies. A combination of discrete wavelet transformation (DWT) and texture algorithms were used to extract relevant features from the thyroid images. These features were fed to different configurations of AdaBoost classifier. The performance of these configurations was compared using receiver operating characteristic (ROC) curves. Our results show that the combination of texture features and DWT features presented an accuracy value higher than that reported in the literature. Among the different classifier setups, the perceptron based AdaBoost yielded very good result and the area under the ROC curve was 1 and classification accuracy, sensitivity and specificity were 100%. Finally, we have composed an Integrated Index called thyroid malignancy index (TMI) made up of these DWT and texture features, to facilitate distinguishing and diagnosing benign or malignant nodules using just one index or number. This index would help the clinicians in more quantitative assessment of the thyroid nodules. PMID- 22054817 TI - A review of transplant immunology. AB - Transplantation has been an accepted treatment for end-stage organ disease for more than 30 years. Advances in transplant immunology are the cornerstone to the success of the body's ability to accept the allografted organ while continuing to perform immune functions such as tumor surveillance and fighting pathogenic organisms. This article describes immunosuppressant regimens and attendant nursing considerations in the care of transplant patients. PMID- 22054818 TI - Pharmacology of immunosuppressive medications in solid organ transplantation. AB - The multitude of immunosuppressants available for solid organ transplantation allows for many combinations of immunosuppressive therapies that can be tailored to a patient's specific lifestyle and immunosuppression needs. Newer agents currently being studied offer even more possibilities for the future to further reduce the incidence of acute rejection and prolong graft and patient survival. PMID- 22054819 TI - Nursing care of the pancreas transplant recipient. AB - Pancreas transplantation has been successful for restoring euglycemia in persons with type 1 diabetes mellitus. The transplantation may be performed as a single procedure, or it may follow or be performed simultaneous with kidney transplantation. This article discusses potential consequences of hyperglycemia and hypoglycemia and indications, alternatives, and contraindications for transplantation. The author also describes postoperative nursing care and potential complications including surgical and immunologic. Potential outcomes of pancreas transplantation can include survival benefit, physiologic improvement, and enhanced quality of life. PMID- 22054820 TI - Liver transplantation: issues and nursing care requirements. AB - Liver transplantation has evolved into an accepted treatment for many suffering from end-stage liver failure. The complex nature of the liver results in every organ system being impacted by either the failing or the transplanted liver. Organ shortage remains problematic, and work to ensure maximizing the organ donor pool as well as the success of each organ transplant continues. The clinical care and condition of the patient before transplant can impact the outcome after transplant. Nurses can play an integral role in early identification of graft dysfunction, rejection, or infection. Because of the intimate and large amount of time that the nurse is at the patient's bedside, he or she is often in a position to monitor for potential risks to the patient and take corrective action. PMID- 22054821 TI - An overview of intestine and multivisceral transplantation. AB - Intestine transplantation remains a formidable clinical and immunologic challenge. With newer immunosuppressive agents and accumulated experience, the survival outcomes for these patients are improving. The relationship of recipient preexisting conditions with the risk of postoperative events clearly emphasize the necessity of early referral of patients with intestinal failure to expert transplant program before the onset of life-threatening complications.30 With increased awareness and knowledge regarding referral criteria, transplant criteria, optimal time for transplantation, and medication regiments, improved patient outcomes after intestine and multivisceral transplant will be achieved. PMID- 22054822 TI - Heart transplantation. AB - Cardiac transplantation remains a life-prolonging process. Survival after heart transplantation has improved despite a sicker incoming patient population. The field of heart transplantation is constantly evolving. Advances in organ preservation, immune monitoring, and improved immunosuppressive regimens will continue to develop over time. The impact of the newest immunosuppressive agents and protocols, improved diagnostic testing, and new management strategies is yet to be determined. The potential of cell therapy is still under evaluation and the field is still in its infancy but rapidly evolving; the key to the future in this field may not be the delivery of the cells themselves but understanding how they interact with one another at a molecular level and, in particular, with resident stem cells in cardiac tissue. In addition to the medical advances, health care professionals need to educate the public about the benefits of transplantation as well. PMID- 22054823 TI - Lung transplant. AB - The ICU period is only one time point among many in the complex, multidisciplinary postoperative management required for patient survival and improved QOL. The care required on step-down units and after discharge to home each has unique care aspects that impact successful patient outcomes. PMID- 22054824 TI - Helping hands: caring for the upper extremity transplant patient. AB - Caring for upper extremity transplant recipients can offer challenges and opportunities to nursing staff in combining new patient procedures, new technologies, and complex patient care needs including unique physical care, monitoring and observation, rehabilitation expectations, and psychiatric/psychosocial support. Medical professionals continue to be apprehensive about the risks of immunosuppressive therapy and the possibility of acute and chronic rejection. The sustained development and research into reliable, reduced-dose immunosuppression or immunomodulatory strategies could expand the life-enhancing benefits of reconstructive transplantation. PMID- 22054825 TI - Transplant infectious disease: implications for critical care nurses. AB - Infection is an important issue for critical care nurses as they care for patients throughout all phases of the transplant continuum: potential organ donors, transplant candidates, and transplant recipients. This article has reviewed salient issues relative to infections in each of these patient populations, including patients with VADs, and has highlighted key points pertaining to bacterial, viral, and fungal infections. PMID- 22054826 TI - Transplantation: past, present, and future. PMID- 22054827 TI - Recent advances in reconstruction and applications of genome-scale metabolic models. AB - In the last decade, reconstruction and applications of genome-scale metabolic models have greatly influenced the field of systems biology by providing a platform on which high-throughput computational analysis of metabolic networks can be performed. The last two years have seen an increase in volume of more than 33% in the number of published genome-scale metabolic models, signifying a high demand for these metabolic models in studying specific organisms. The diversity in modeling different types of cells, from photosynthetic microorganisms to human cell types, also demonstrates their growing influence in biology. Here we review the recent advances and current state of genome-scale metabolic models, the methods employed towards ensuring high quality models, their biotechnological applications, and the progress towards the automated reconstruction of genome scale metabolic models. PMID- 22054828 TI - Detection of oestrogen residues in meat by radioreceotor assay. AB - A radioreceptor assay, suitable for detecting residues in the meat of any compound with oestrogenic activity, is described. The assay is based upon the use of a purified preparation of oestrogen receptors obtained by affinity chromatography from swine uteri. The method was validated by measuring the oestrogenic activities in plasma and meat of diethylstilboestrol or oestradiol treated calves. The standard curve was performed by using oestradiol. Plasma levels of oestrogenic activity, expressed as equivalent of oestradiol, rose above control values 2 days after both diethylstilboestrol and oestradiol treatments, then declined to basal values by day 6 after the treatments. The levels of oestrogenic activity 10 days after treatment, found in the meat of diethylstilboestrol treated animals, were significantly higher than those found in control animals. No differences were found, however, between meat samples of control and oestradiol treated animals. PMID- 22054829 TI - The effect of electrical stimulation on the quality of three bovine muscles. AB - Meat bulls were randomly assigned to five treatment groups-intermittent electrical stimulation at 300 V (ES) at 5 min and 35 min post mortem (intact carcasses), 35 min post mortem (split carcasses) and non-stimulated controls (NS) (intact and split carcasses). Stimulated carcasses in all groups showed a significantly more rapid pH fall during the first 8h post mortem in adductor (AD), longissimus dorsi (LD) and triceps brachii (TB) muscles. Cooling rates were relatively slow. Samples were removed from the carcass at 24h post mortem. After vacuum storage at 3 degrees C for 6 days stimulated muscles showed lower drip (LD and TB) and heating loss (TB), lower shear force values (AD, LD and TB) and higher taste panel scores (AD, LD and TB) compared with NS controls. No significant differences in tenderness were observed between the three ES groups. Sarcomere length assessment showed more contraction in NS carcasses, particularly in the superficially located LD and TB. These results suggest that cold shortening may occur in some muscles under cooling conditions so far considered safe in this respect. Since higher drip losses coincided with lower sarcomere lengths in these (NS) muscles, it is suggested that, under these conditions, ES may mask the increased drip losses which are possibly the result of muscle contraction. Furthermore, ES prevents the occurrence of cold shortening and, in addition, may exert some 'extra tenderising effect', which is not related to splitting of the carcass nor restricted merely to the LD muscle. PMID- 22054830 TI - Effect of electrical stimulation on veal quality. AB - In three experiments involving a total of eighty-eight veal calves raised in groups and with access to straw, plasma hemoglobin (Hb) levels were determined at one week ante mortem. In each experiment, animals with similar Hb levels were paired. One animal of each pair was stimulated electrically (ES) post mortem whereas the other remained non-stimulated (NS). ES resulted in a more rapid pH fall in longissimus and semi-membranosus muscle. Carcass lean colour scores were improved at 24h, but not at 40 min, post mortem. At 24h post mortem longissimus muscle from ES carcasses showed a brighter colour, lower sarcomere length and lower protein solubility. No significant differences were observed in total haem pigment. After vacuum storage at 3 degrees C for 6 days, samples from ES carcasses had a brighter colour, higher drip and heating loss, lower maximum shear force values, and better ranking and scoring in taste panel preference tests than NS samples. The data indicate that a certain degree of denaturation of the sarcoplasmic proteins may be responsible for the observed effects of ES on water retention and muscle colour, while the improvement of tenderness in the present experiment was due to the prevention, by the treatment, of cold shortening. It is suggested that ES may possibly contribute to the introduction of alternative veal production methods, and thus improve animal welfare. PMID- 22054831 TI - The estimation of sheep carcass composition from fat and muscle thickness measurements taken by probes. AB - Three trials, involving a total of 290 lambs, were carried out to examine the precision of probed fat and muscle measurements for estimating carcass composition in classification and grading schemes. The measurement positions and probes were not always the same in different trials but common measurements provided the basis for comparison between trials. Residual standard deviations (sd) for the prediction of carcass lean percentage averaged over trials are referred to in this Summary. Residual standard deviation for prediction from carcass weight was 3.5. The visual fat assessment currently used in the national Sheep Carcase Classification Scheme, operated by MLC, contributed significantly to the prediction (residual standard deviation = 3.0) but was less precise than a visual assessment of carcass subcutaneous fat content to the nearest percentage unit (SF(e)) (residual standard deviation = 2.6). Fat thickness measurements taken over the M. longissimus at the 12th rib with the Danish optical probe, a simple steel rule or the pig version of the Hennessy Grading Probe (HGP), showed similar precision to the classification fat class. An M. longissimus thickness measurement taken by the HGP did not add significantly to the precision. Probe fat measurements added significantly to the precision achieved with visual fat assessments (residual standard deviation with classification fat class = 2.8; residual standard deviation with SF(e) = 2.5). There would be advantages, therefore, in using both a visual fatness assessment and fat measurements in classification. PMID- 22054832 TI - Changes in extensibility of raw beef muscle during storage. AB - The mechanical properties of raw meat under tension were studied to characterise the factors responsible for tenderisation during storage. Extensibility and irreversible lengthening in the direction of muscle fibres was determined continuously from 2 h to 10 days after stunning by cycling the muscle between two applied forces. In post-rigor meat, extensibility increased slightly and the muscle lengthened by 40%. Lengthening occurred earlier at higher post-rigor temperatures and was more sensitive to changes in temperature than the changes in texture of cooked meat. Increasing the maximum applied stress also caused lengthening to occur earlier in post-rigor meat. No lengthening was detected pre rigor. The relationship between the maximum applied stress and the rate of lengthening showed that lengthening would not have occurred with a stress of 0.07 Ncm(-2) or less. These findings suggest that weakening which occurs during conditioning commenced at rigor and that the component responsible for tenderising was about 30 times weaker than indicated using previous techniques. Histological sections showed regular cracks spaced at about 17 MUm apart. This was believed to be indicative of the involvement of extracellular components in the texture of conditioned meat. PMID- 22054833 TI - Extrusion studies of mixtures containing certain meat offals: Part 2-textural properties. AB - Thermoplastically extruded products prepared from soy grits alone, and from those containing 20% or 35% of bovine or porcine offal, at various temperatures of extrusion, were subjected to instrumental texture profile analysis (hardness, elasticity, cohesiveness, gumminess, chewiness) and shear force measurements. The offal sources were untreated, or alkali-extracted, protein from bovine and porcine lung and bovine tripe (rumen and reticulum) and protein in extracted by sodium dodecyl sulphate (SDS) from bovine tripe. For products prepared from soy grits alone, hardness, gumminess, chewiness and shear force showed maxima at 170 degrees C, whereas elasticity and cohesiveness increased progressively in the temperature range studied (140-190 degrees C). Products containing SDS-extracted tripe protein required more force to shear, and were more hard, gummy and chewy, than products containing untreated offal, and values for all parameters were greater in the latter than in products containing alkali-extracted offal protein. The effect of extrusion temperature on the textural parameters of the products was less than that due to the mode of offal preparation used (untreated, alkali- or SDS-extracted) or the level of incorporation. Offal source was relatively unimportant. Products containing alkali-extracted offal protein had poor internal structure and were brittle; those containing SDS-extracted protein were tough. The different textural properties of the extracted products might determine their relative suitability for use either alone, as analogues or as extenders. PMID- 22054834 TI - A morphological and biochemical examination of the hydrothermal denaturation of collagen. AB - The morphological changes occurring during the hydrothermal denaturation of collagen obtained from the tendinous sheath of the longissimus dorsi muscle of mature sheep have been examined. To investigate the influence of the physical state of the collagen on its subsequent denaturation, collagen has been heated in the form of isolated fibrils, small pieces of unrestrained tissue and strips of tissue restrained from contracting fully during heating and cooling. The morphological changes occurring during denaturation and the thermal stability of the collagen to melting have been found to be dependent on the physical state of the collagen, the thermal stability of collagen being lowest in isolated fibrils, intermediate in unrestrained pieces, and highest in restrained samples. In conjunction with the morphological studies, the extent of dissolution of collagen by heat alone and the susceptibility of collagen to pronase digestion were measured and examined as possible biochemical criteria for assessing the extent of thermal denaturation of collagen. PMID- 22054835 TI - Chemical and physiological aspects of pig stunning in relation to meat quality-A review. AB - A survey of research undertaken at the Research Institute for Animal Husbandry 'Schoonoord' is given in which different stunning methods have been evaluated with respect to metabolic, meat quality and economic aspects. These data have been supplemented from the literature. The overall conclusion is that electrical stunning (300V) with short stunning time and a minimal lapse of time between stunning and sticking, offers the best prospects in relation to pork quality. Electrical stunning is thus recommended for pigs in industrial scale slaughtering. PMID- 22054836 TI - The nutritive value of protein isolates and fibres from meat industry by products. AB - Protein isolates extracted from rumen, lung and plasma by alkaline solubilisation were spun into protein fibres and were evaluated for protein quality by rat feeding trials and by amino acid analyses. The net protein utilisation (NPU) of the fibres ranged from 53.0 to 76.9 for plasma and rumen fibres respectively, methionine plus cystine and valine being limiting amino acids. Lysine was not found to be a limiting amino acid in any sample and lysine availability was high in isolates and fell only slightly on spinning. There was a marked discrepancy between chemical score and NPU for rumen isolate and it is postulated that an anti-nutritional factor, possibly a trypsin inhibitor, normally present in bovine organs, could be active in the isolate by lowering methionine availability to the animal and decreasing NPU. Spinning the proteins, however, either destroys the inhibitor or decreases its concentration since NPU and chemical score become equal. PMID- 22054837 TI - Effect of prolonged fasting upon the calcium activated sarcoplasmic factor of rabbit skeletal muscle. AB - Adult male New Zealand rabbits were subjected to a 28-day fast (food deprivation). Various blood biochemical parameters, as well as organ and individual skeletal muscle (semitendinosus and longissimus dorsi) weights, were determined. Additionally, the effect of fasting upon individual skeletal muscle functions was assessed. The calcium activated sarcoplasmic factor (CASF) isolated from the fasted rabbits was compared with the same enzyme isolated from ad lib fed rabbits. The fasted rabbits yielded greater amounts of CASF of a slightly higher specific activity than the same enzyme derived from ad lib fed rabbits. However, the enzymes from both treatments exhibited similar activities on intact myofibrils, as demonstrated by phase contrast microscopy and SDS-polyacrylamide gel electrophoresis. PMID- 22054838 TI - Electrical stimulation, muscle tension and glycolysis in bovine Sternomandibularis. AB - Electrical parameters previously employed to hasten the onset of rigor mortis in carcasses were derived empirically. Various parameters have been studied to determine their relationship to the two-stage fall of muscle pH resulting from stimulation. At any given stimulation period pulse frequency had a considerable effect on the magnitude of the pH fall that occurs during stimulation, the greatest falls, ~ 0.7 pH units in a 120 sec period, being achieved with 5 to 16.6 pulses. sec(-1). The same total number of pulses delivered at differing frequencies did not produce pH falls of equal magnitude. Variation in pulse shape and polarity caused minor changes. Increased energy levels per pulse increases the magnitude of the pH fall during stimulation. All stimulation parameters tested resulted in the rate of pH fall after stimulation being one and a half times to twice that of non-stimulated muscle. The tension-time curves obtained with lower frequencies (< 10 pulses . sec(-1)) show incomplete summation of pulses with sustained tension. At higher frequencies a complete tetanus develops, while tension falls rapidly soon after achieving the peak tension. The relationship between the mechanical and biochemical responses and the implications for stimulation as a practical processing method are discussed. PMID- 22054840 TI - Erratum. PMID- 22054839 TI - Studies on the meat production characteristics of Botswana goats and sheep -part III: Carcase tissue composition and distribution. AB - In this paper data concerning the tissue composition and distribution in the carcases of Botswana smallstock (goats and sheep) of different age and sex groupings are discussed. These data were collected for use in the Botswana Smallstock Improvement Programme, which is designed to improve meat production from the indigenous goats and sheep of Botswana. This programme, together with the data on live measurement, general body composition and carcase joint composition, has been described in the previous papers in this series. The data presented showed that, generally, indigenous Botswana sheep were fatter and earlier maturing than goats at similar ages. The sheep were still found to be significantly fatter when the data were statistically analysed and corrected for differences in empty body weight. In the case of the milk tooth male goats, castration increased the rate of maturity and the level of fat in the carcase. Similar data obtained on male Boer goats (which are to be used as a meat improver breed) showed that these animals produced both bigger and leaner carcases than indigenous goats of similar age. These differences were significant when the two groups were compared statistically after corrections for body weight differences. PMID- 22054841 TI - Electrical stimulation during exsanguination: Effects on the prevalence of blood splash and on sensory quality characteristics in veal. AB - Twenty-four veal calves were stunned with a captive bolt. Twelve calves were shackled by the left, the other twelve by the right hindleg. Approximately 1 min after sticking, six carcasses of each of these subgroups were stimulated electrically with equipment relying on a combined high (3000 V, 0.83 pulses s( 1), 1.5 ms duration) and low 35 V, 14 pulsess(-1)) voltage action. The remaining carcasses were left unharmed. At 24 h post-mortem hindquarters were boned to commercial primal cuts. Surrounding connective tissue and cut-up surfaces of primals as well as certain locations vulnerable for blood splash were further dissected. Neither electrical stimulation nor shackling by either of the hindlegs significantly affected the prevalence and severity of blood splash. Post-mortem factors promoting blood splash and possibly related to electrical stimulation and shackling are discussed. At 7 days post-mortem the sensory meat quality was assessed. In general, electrical stimulation did not significantly affect waterbinding and colour characteristics in longissimus (M. longissimus dorsi) and semimembranosus samples. Sarcomere lengths were similar in stimulated and control groups in longissimus but not in semimembranosus muscle. In both muscles shear force values were lower after electrical stimulation. In general, neither longissimus nor semimembranosus samples excised ipsilaterally from the shackled leg side exhibited differences in tenderness and sarcomere length. It is concluded that shackling by one leg or the other does not interfere with the tenderising effect of electrical stimulation. PMID- 22054842 TI - NMR relaxation of water protons in normal and malignant hyperthermia-susceptible pig muscle. AB - (1)H-NMR has been used to study the evolution of water proton transversal relaxation times in ageing skeletal muscles of normal and halothane-positive Pietrain pigs. Malignant hyperthermia was confirmed by the caffeine contracture test. Lactic acid, creatine phosphate, and ATP levels in muscle biopsies were measured by biochemical analysis. The NMR dynamic results revealed malignant hyperthermia, but knowledge of animal age and muscle type improved significantly the detection ability. The NMR results revealed large differences between muscles. Halothane sensitivity detection seems to be less affected by animal age, than by muscle effect but discrimination was more efficient in the older animal group. It is concluded that (1) H-NMR is a suitable method for diagnosing halothane sensitivity on a well identified muscle biopsy and that water dynamics might be related to acidosis in muscle fibres. PMID- 22054843 TI - Early post-mortem degradation of intramuscular collagen. AB - Post-mortem changes in physical and thermal stabilities of bovine intramuscular connective tissue were studied during the first 24 h postmortem. Collagen thermal shrinkage temperature (T(s)) decreased (P < 0.01) and collagen solubility increased (P < 0.01) during the first 24 h following slaughter with greatest amount of change occurring in the first 8 h post mortem. The dynamic nature of intramuscular connective tissue during the very early post-mortem (VEP) period is compared to the VEP-tenderness relationships proposed by Marsh and others. PMID- 22054844 TI - Effect of exercise and pre-slaughter stress on pork muscle characteristics. AB - The effects of exercise, stress and chill temperature on pork muscle characteristics were studied in a 3 * 2 * 2 factorial experiment in which treatments were assigned to blocks made up of six pigs of the same sex from the same litter. Pigs were fed a corn-soybean meal diet with the two littermate pigs on each treatment fed together. Treatments were (1) a control group receiving no exercise and fed in an 8 m(2) pen; (2) a treatment group fed in an 8 m(2) pen and driven 1.6 km/day for 100 days prior to slaughter; and (3) a treatment group fed in pens with 40 m(2) floor space with feeders placed 5 m from their waterers. When the animals averaged approximately 105 kg in weight, one animal from each pair treated alike was subjected to standardized stress. After slaughter, one side was chilled at 2-3 degrees C and the other at 13-15 degrees C for 24 h. Both sides were then chilled at 2-3 degrees C for an additional 24 h. Exercise did not affect average daily gain (ADG), feed efficiency, yield of total wholesale cuts, muscle pH, protein solubility, fiber diameter and sarcomere length of the Longissimus dorsi (LD) and Quadriceps femoris (QF) muscles or the tenderness of the QF muscle. Exercise decreased backfat thickness and the subjective tenderness of the LD muscle. The effects of stress on the characteristics evaluated were consistent with those that have been previously reported. Chilling temperature and interactions involving chilling temperature did not affect any of the characteristics studied. No exercise * stress interactions were observed. Protein solubility values indicated that pale, soft exudative (PSE) muscle was not a factor in any of the treatments. It was concluded that exercise will produce leaner carcasses but less tender muscle and that exercise will not counteract the effects of pre-slaughter stress. PMID- 22054845 TI - The surface active properties of myosin and its proteolytic fragments. AB - The surface active properties of myosin and its proteolytic fragments, light meromyosin (LMM), heavy meromyosin (HMM), subfragment-1 (S-1) and myosin rod, at initial bulk phase concentrations in the range of 10(-4)% to 10(-2)% w/v were determined by the drop volume method. Overall, S-1 was the most effective surface tension depressor, whereas the tail portions of myosin, i.e. LMM and myosin rod were less surface active than the parent myosin molecule. The surface pressures attained after 40 min, at an initial bulk phase concentration of 10(-2)% (w/v), were 22.00, 21.77, 21.02, 16.77 and 16.77 mNm(-1) for S-1, HMM, myosin, LMM and myosin rod, respectively. Furthermore, S-1 effected the most rapid change in surface pressure during the initial 5 min period. PMID- 22054846 TI - Reaction of nitrite with ascorbic acid and its significant role in nitrite-cured food. AB - The decrease in concentration of free nitrite in an aqueous reaction solution made by mixing nitrite and ascorbic acid was studied. This decrease resulted information of a reaction product which transferred NO to ferricytochrome c to form ferrocytochrome c nitroso compound. From the solution containing the reaction product, nitrite could be regenerated spontaneously and suddenly by physical agitation. Oxygen was apparently not necessary for regeneration nitrite from the reaction solution. It does not seem that the regeneration of nitrite was responsible for a bimolecular dismutation of nitrosoascorbic acid in a reverse direction proposed by Fox and Thomson (Biochemistry2, 465; 1963). Heating of the reaction solution at less than 100 degrees C resulted in a loss of nitrite from the solution, which was greater with increasing concentration of ascorbic acid. The reaction product formed between nitrite and ascorbic acid is probably responsible not only for nitrosation reactions, but also for the loss of nitrite observed during curing of meat. PMID- 22054848 TI - Animal by-product processing By H. W. Ockerman & C. L. Hansen. Ellis Horwood Series in Food Science and Technology, VCH Verlagsgesellschaft, Weinheim, 1988. 366 pp. Price: (DM 250) L88. PMID- 22054847 TI - Effect of chilling on the hardness of fat on sides of beef. AB - The effect of chilling procedure on the resulting hardness (i.e. cutability) of subcutaneous adipose tissue (fat) on sides of beef has been objectively investigated using a sliding pin consistometer (SPC). Instrument readings obtained from a model system of samples of beef dripping (made with subcutaneous adipose tissue and kidney fat but without added bone trim) indicated fat hardness could be significantly (P < 0.05) influenced by chilling procedure. However, for sides from 19 grass-fed animals which were chilled using either a 'hot' or 'cold' extreme treatment which would comply with current Australian Regulations (i.e. 20 degrees C deep butt temperature in 20h) there was no significant difference 20 h post mortem between the hardness of the fat at a temperature of 10 degrees C. It would appear, therefore, that the hardness of the fat on sides of chilled beef cannot be managed through manipulation of the chilling procedure in conventional processing. PMID- 22054851 TI - Prognostic risk factor evaluation in patients with relapsed or refractory multiple myeloma receiving lenalidomide treatment: analysis of renal function by eGFR and of additional comorbidities by comorbidity appraisal. AB - INTRODUCTION: Renal impairment (RI) is a dreaded complication in multiple myeloma (MM) and has been associated with decreased progression-free survival (PFS) and overall survival (OS). METHODS: Forty-five consecutive patients with MM received lenalidomide therapy combined with either dexamethasone or standard chemotherapy, with dose modification according to current guidelines. Comorbidity indices (hematopoietic cell transplantation-specific comorbidity index [HCT-CI], Kaplan Feinstein [KF], and the Freiburg comorbidity index [FCI]) were analyzed and renal function was determined by estimated glomerular filtration rate (eGFR) before lenalidomide treatment and 1, 3, and 6 months after treatment. RESULTS: The median patient age was 66 years. Pretreatment was substantial with >= 2 treatment lines in 71% of patients. Lenalidomide induced median PFS and OS of 13 and 25 months, respectively. The analysis of comorbidity scores identified only the FCI as significant, with different PFS for low-risk vs. high-risk patients of 20 vs. 9 months (p = .0036) and OS of not reached vs. 12.8 months (p < .0001), respectively. Although baseline renal function by serum creatinine evaluation appeared normal (median 1.0 mg/dL), mild RI was readily detectable by eGFR (median 83 mL/min/1.73 m(2)). When patients without RI were compared with those with mild, moderate, and severe RI, 1- and 2-year PFS rates were similar (hazard ratio [HR] with decreasing eGFR, 1.028; p = .6927). For OS, the HR of 1.192 indicated decreased survival probabilities with deteriorating eGFR (p = .0411), which was perceived by eGFR but not serum creatinine assessment (p = .2253). CONCLUSIONS: Lenalidomide was well tolerated in intensively pretreated and elderly MM patients, including those with RI. PFS was not significantly different in patients with decreasing eGFRs, albeit RI and other comorbidities remained significant for OS. PMID- 22054853 TI - [Results of a capacitation process of personnel involved in a clinical program of hematopoietic progenitors transplantation]. PMID- 22054852 TI - [Translation and adaptation to Spanish language of the quality of life questionnaire for sleep apnea-hipopnea syndrome Quebec Sleep Questionnaire]. AB - BACKGROUND AND OBJECTIVE: The objective of this study was to translate and adapt to Spanish the Quebec Sleep Questionnaire (QSQ). METHODS: For QSQ tran-cultural adaptation, the back-translation technique was used. A psychologist and a pneumonologist made a first translation of the questionnaire. Naturalness correctness of items and conceptual equivalence were evaluated by external researchers and a group of patients. A back-translation was finally remitted to author. RESULTS: Most of the items had minimal difficulty in translation. The difficulty was moderate in only 4 of them (items 2, 7, 8, 30). Naturalness correctness was maximal in most items and excellent in 4 (8 to 9 points). The conceptual equivalence was complete in all the items, except item 2 that showed a partial equivalence. CONCLUSIONS: The first translation and adaptation to Spanish language of the quality of life questionnaire QSQ has been done. The translation has minimal difficulty and the conceptual equivalence is almost complete. PMID- 22054854 TI - Editorial. PMID- 22054855 TI - Further studies on bovine muscle composition. AB - The average occurrences of fibre types, I,IIA and IIB in the longissimus dorsi (LD) of female cattle were 18%, 59% and 23%, respectively. The IIB occurrence lay between that for bulls and steers, reported in Young & Bass (1984). Since IIB fibres were absent from the splenius (Sp) of females, its composition was more akin to that of bulls than steers. However, the relative area of I and IIA fibres in female Sp was more like that of steers than bulls since IIA fibres were not disproportionately large in females. Evidence suggests that the occurrence of type I (or II) fibres in the LD is rather static and that changes in the occurrence of IIA fibres, reciprocal to IIB, are more common, irrespective of sexual status-bull, steer or female. The route by which IIA and IIB fibres interconvert is discussed. In animals where both the LD and Sp were sampled, the fibre composition of one muscle was a poor predictor of the other's composition. The correlation between the occurrence of I fibres in Sp and succinate dehydrogenese activity in whole muscle was poor, and reasons are advanced to explain this unexpected result. When dark-cutting muscles were excluded from analysis, the average ultimate pH of LD muscles was lower than that of Sp. This result was consistent with the higher type II fibre content of the LD. Ultimate pH of Sp muscles was correlated with occurrence of I fibres, but in the LD a similar relationship could not be established. A link between occurrence of IIB fibres and proneness to the dark-cutting condition is suggested. PMID- 22054856 TI - Lipid oxidation and metmyoglobin formation in sausages containing chickpea flour. AB - Rapid lipid oxidation and metmyoglobin formation in sausages containing up to 30% chickpea flour is due to the presence of lipoxidase in chickpea flour. This enzyme oxidises the unsaturated fats present to peroxides (or related compounds) which then catalyse myoglobin oxidation. Heat treatment of chickpea flour at 80 degrees C for 1 h in water prior to its addition to the batter will prevent both accelerated lipid and myoglobin oxidation in these sausages. An antioxidant containing alpha-tocopherol and ascorbyl palmitate inhibited the lipid oxidation in these products but had no effect on myoglobin oxidation in sausage batter containing unheated chickpea flour. The relevance of these results to the interdependence of lipid and myoglobin oxidation in meat and meat products is discussed. PMID- 22054857 TI - Number and distribution of bacteria on some beef carcasses at selected abattoirs in some member states of the European communities. AB - In seven member countries of the European Communities, three abattoirs were visited on three occasions in each of two surveys and at each visit ten beef carcasses were sampled, before chilling, at defined sites on the neck, brisket, forerib and medially on the round. In Survey I, samples were plated for total viable count (TVC) at 30 degrees (ISO 2293) and Enterobacteriaceae at 37 degrees (ISO 5552); in Survey II only TVCs were made. This paper is confined to analyses of the TVCs in the two surveys. Data from each country were analysed separately as sampling methodology may not have been sufficiently reproducible by different workers to allow between-countries comparison. Variations among visits to particular abattoirs and abattoir * site interactions made comparisons among abattoirs invalid within five of the seven countries. To effectively monitor differences between abattoirs within most countries it would be necessary to make more than three visits to each abattoir. Despite abattoir * site interactions in three countries in Survey I and four countries in Survey II, comparisons between sites were generally valid because of the consistent high contamination of the brisket. In the remainder of countries the abattoir * site interaction was too large to allow valid comparisons between sites. It is recommended that at least three or four sites are sampled in future surveys as only one site per carcass would underestimate the number of more heavily contaminated carcasses. PMID- 22054858 TI - Effects of low-frequency electrical stimulation on beef tenderness. AB - The application of 2 Hz, 500 V electrical stimulation to early post-mortem beef sides causes rapid muscle glycolysis, yet produces no trace of the extensive tissue rupture effected by 60 Hz current. By means of this low frequency technique, coupled with a mild or delayed-chill routine, we have examined the supposed tenderizing effect of rapid pH decline alone, without concurrent fiber fracture or cold-shortening intervention. Loin steaks from sides receiving this treatment were significantly tougher than those from paired control sides, an observation strongly suggesting that tenderization is hindered by rapid glycolysis. In other experiments, 60 Hz 500-V current was found to produce very extensive fracturing with breaks appearing (on average) every 6 mm of fiber length; this treatment resulted in a very significant tenderizing relative to that observed in the unstimulated control sides. It is concluded that, apart from its ability to prevent cold-shortening, normal-frequency high-voltage stimulation exerts its beneficial tenderizing action by fracturing the fibres; the accompanying acceleration of glycolysis actually causes a small, but definite, negative effect on eating quality. PMID- 22054859 TI - Effects of reaction variables on the hydrolysis of lean beef tissue by alcalase. AB - The effects of the reaction variables, pH, time, temperature, enzyme: meat ratio and meat concentration, on the hydrolysis and solubilisation of lean meat protein by Alcalase have been determined. Experiments were performed with both dilute meat suspensions and undiluted ground meat. Reaction progress curves were similar to those for the enzymic hydrolysis of other proteins, with rapid initial reaction rates followed by a gradual decline in rate. The optimum reaction pH was 8.5. Optimum temperatures were found to be 55 degrees C for the hydrolysis reaction and 60 degrees C for meat solubilisation. Both solubilisation and degree of hydrolysis increased with increasing enzyme concentration. At an enzyme: meat ratio of 80 mg Alcalase 0.6L per gram of dry meat, a solubilisation of 94% and a degree of hydrolysis of 18% were achieved after a 3-h reaction period. As meat concentration was increased, degree of hydrolysis decreased slightly and solubilisation decreased markedly. PMID- 22054861 TI - Eating quality of European beef assessed at five research institutes. AB - Loin steaks from 10 animals (five of each of two types) from each of eight European countries were assessed for eating quality at five institutes in Denmark, Ireland, England, France and the Federal Republic of Germany. All panels found wide variation in eating quality and many of the steaks were unacceptably tough. Although attempts to relate quality to production factors were often confounded, differences in post-slaughter handling, particularly between producing countries, dominated eating quality. Breed, sex, age or fatness had relatively little influence on eating quality in this trial. A common eight category scale of tenderness/toughness was used in addition to each institute's usual descriptive scales for tenderness, flavour, juiciness and overall acceptability, employing four to eleven categories. Within panels, attribute scores were not independent and tenderness and flavour in combination were the best predictors of overall acceptability. Between panels, tenderness was highly interrelated, flavour and juiciness poorly interrelated. These findings, together with estimates of each panel's discrimination and the variation between individual assessors, are discussed in relation to standardisation and equivalence of sensory methodology. PMID- 22054860 TI - Primary intraosseous myoepithelioma arising in the iliac bone and displaying trisomies of 11, 15, 17 with del (16q) and del (22q11)--A rare case report with review of literature. AB - Mixed tumors are uncommonly observed in the musculoskeletal system, where they form a common spectrum with a myoepithelioma and a parachordoma. Herein, we present a rare case of a mixed tumor/myoepithelioma arising in the iliac bone of a young adult male who presented with swelling in his right hip. Radiological imaging disclosed a large, intraosseous, lytic, heterogenous mass with a soft tissue component. Biopsy and subsequent tumor resection showed an 18cm sized tumor involving the iliac bone and soft tissues and comprising polygonal and spindly cells, arranged in cords and aggregates, embedded in a myxohyaline stroma with osteochondroid differentiation. Tumor cells exhibited mild nuclear variation, rare mitotic figures, focal cytoplasmic clearing, and prominent squamous differentiation. On immunohistochemistry (IHC), tumor cells were diffusely positive for S100-P, EMA, CK5/6, p63, GFAP, calponin, and focally positive for CK/MNF116, but negative for Brachyury/T. Diagnosis of a myoepithelioma/mixed tumor was offered. Further, cytogenetic analysis revealed lack of EWSR1 gene rearrangement and showed clonal trisomies of 11, 15, 17 with del (16q) and del (22q11). The present case is a rare documentation of a myoepithelioma in the appendicular bones and the second such case identified in the iliac bone. IHC and cytogenetic findings supported a myoepithelial cell origin, and reinforced its relationship with a parachordoma and its distinction from mixed salivary gland tumors, a chordoma, and an extraskeletal myxoid chondrosarcoma that form its differential diagnoses. PMID- 22054862 TI - Influence of the addition of mechanically recovered meat on the physico-chemical properties of meat model blends. AB - The physico-chemical properties of meat model blends (basic composition: fresh lean pork, pork back fat, 2% NaCl, water with ice), with added mechanically recovered pork (MRM), were studied. Fresh MRM was added at levels of 10% and 20% substitution of meat protein with or without further substitution by 10% sodium caseinate or soya isolate. The addition of MRM to meat blends caused an increase in the pH, the water-holding capacity, the viscosity, the dominant wavelength and colour purity. No effects on emulsifying capacity were observed but thermal cooking losses and lightness of colour were reduced. The addition of blends of MRM and soya isolate or sodium caseinate caused lower values of the investigated features than those observed when only MRM was used. PMID- 22054863 TI - The role of lipids and glycerol in determining the shelf-life of glycerol desorbed intermediate moisture meat products. AB - During storage of glycerol desorbed intermediate moisture beef at 38 degrees C the marked loss of eating quality, demonstrated by increasing loss of nitrogen solubility in sodium dodecyl sulphate (SDS) plus beta-mercaptoethanol, loss of haemoprotein character, decrease in pH and the formation of water-soluble hydroxyproline containing fragments, is not markedly affected by the presence of oleic acid and/or butylated hydroxytoluene. In addition, gas-liquid chromatographic analysis of the lipid fractions suggests that, in these meats, the relative composition of the neutral phospholipid fractions does not change to any marked extent during storage. However, the TBA and peroxide values, which are very high in the freshly prepared meats, do decrease quite markedly during storage. Consideration of these results suggests that, in glycerol desorbed meats, glycerol oxidation products are the major reactants leading to loss of eating quality. PMID- 22054864 TI - Muscle fibre deformation: rigor extensibility of raw bovine muscle. AB - Muscle which entered rigor restrained in a stretched condition shortened when freed, resulting in three types of wrinkling-(1) fibre wrinkling, (2) myofibril wrinkling and (3) myofilament wrinkling. The structural consequences of stretching muscle whilst it was in rigor were studied by light and electron microscopy. Rigor extension of contracted or stretched samples in excess of that required to straighten any wrinkles resulted in three types of damage to a high proportion of the sarcomeres. (1) Breaks occurred in the I bands, but not the clean breaks associated with post-rigor muscle. (2) Breaks occurred in the A bands on either side of the M line. (3) Z lines were pulled apart. PMID- 22054865 TI - Problems associated with commercial lamb washing in Ireland. AB - Three methods for cleaning lamb carcasses were compared in an Irish export factory: (1) hot water (85-90 degrees C) sprayed at high pressure (7 kg/cm(2)) (MRI), (2) a pneumatic gun using water at 40-50 degrees C and 7 kg/cm(2) pressure and (3) soiled areas of the carcass were scrubbed with a nylon or bristle brush. Bacteriologically, the MRI method was marginally better than brushing but this had no effect on the ultimate shelf-life of the carcasses, which, in the prevailing conditions, was 8 days. All methods produced visually clean carcasses with good bloom. Both spray washing methods were considered impractical under commercial conditions, mainly because they were too slow. PMID- 22054866 TI - Electroencephalographic studies of stunning and slaughter of sheep and calves: Part 1-The onset of permanent insensibility in sheep during slaughter. AB - The time of onset of permanent insensibility, subsequent to incision of the major blood vessels of the neck, was studied in sixteen adult sheep and five one-week old lambs. Insensibility was determined from the study of electroencephalograms (EEG) and interpretation was based on the amplitude and pattern of fast wave signals of a transhemispheric bipolar derivation. In both adult sheep and lambs, conscious at the time of slaughter, insensibility occurred within 2 to 7 s and EEG traces became isoelectric between 10 and 43 s. In sheep which were lightly anaesthetised at the time of slaughter, EEG traces became isoelectric between 18 and 70 s after incision of the major blood vessels of the neck. In one sheep which was slaughtered by severance of the carotid artery and jugular vein on one side of the neck only, the onset of insensibility was delayed for 29 s. In the majority of animals, the electrocardiogram (ECG) continued to show a normal pattern for more than 10 min after slaughter. There was an initial rise in blood pressure in the first 5 to 7 s and it remained elevated for a further 10 to 20 s. The results of this work are discussed with reference to definition of death appropriate for statutory purposes and the implications for the humane slaughter of sheep. PMID- 22054867 TI - The effect of temperature and ultimate pH on the increase in meat toughness resulting from restraint during cooking. AB - Samples of stretched muscle cooked at 50, 60, 70 or 80 degrees C, while restrained at either their original pre-cooking length or further tensioned at about 130% of their original pre-cooking length, had significantly (P < 0.001) greater Warner-Bratzler (WB) peak shear force values for all temperatures than similar samples cooked without restraint except for those restrained at their original length and cooked at 50 degrees C. Restraint during cooking at 80 degrees C increased the peak shear force values of stretched sheep muscles with ultimate pH values in the range 5.5-7.0. This increase, which has been related to connective tissue strength, was not significantly related to ultimate pH. Both initial yield and peak force values, for samples cooked either restrained or unrestrained, decreased significantly (P < 0.001) and at similar (not significantly different) rates with increase in ultimate pH. PMID- 22054868 TI - Meat and meat products: Factors affecting quality control Edited by N.R.P. Wilson, Applied Science Publishers Ltd, London and New Jersey. ix + 207 pp. 1981. Price: L16.00. PMID- 22054869 TI - Meat in nutrition and health Edited by K.R. Franklin and P.N. Davis, National Livestock and Meat Board, USA. Price not quoted. PMID- 22054871 TI - GSPE interferes with tau aggregation in vivo: implication for treating tauopathy. AB - Tauopathies are characterized by progressive neurodegeneration caused by intracellular accumulation of hyperphosphorylated tau protein aggregates in the brain. The present study was designed to test whether a grape seed polyphenolic extract (GSPE) previously shown to inhibit tau protein aggregation in vitro could benefit tau-mediated neuropathology and behavior deficits in JNPL3 transgenic mice expressing a human tau protein containing the P301L mutation. Nine-month-old JNPL3 mice were treated with GSPE delivered through their drinking water for 6 months. We found that GSPE treatment significantly reduced the number of motor neurons immunoreactive for hyperphosphorylated and conformationally-modified tau in the ventral horns of the spinal cord identified using AT100, PHF-1, AT8, and Alz50 tau antibodies. This coincided with a drastically reduced level of hyperphosphorylated and sarcosyl-insoluble tau in spinal cord fractions. Furthermore, the reduction of tau pathology was accompanied by an improvement in the motor function assessed by a wire hang test. Collectively, our results suggest that GSPE can interfere with tau-mediated neurodegenerative mechanisms and ameliorate neurodegenerative phenotype in an animal model of tauopathy. Our studies support further evaluation of GSPE for preventing and/or treating of tauopathies in humans. PMID- 22054872 TI - Healthy aging attenuates task-related specialization in the human medial temporal lobe. AB - Recent research on aging has established important links between the neurobiology of normal aging and age-related decline in episodic memory, yet the exact nature of this relationship is still unknown. Functional neuroimaging of regions such as the medial temporal lobe (MTL) have produced conflicting findings. Using functional magnetic resonance imaging (fMRI), we have recently shown that young healthy individuals show a stronger activation of the MTL during encoding of objects as compared with encoding of positions. Using the same encoding task, the present study addressed the question whether this greater MTL activation during encoding of objects varies with age. Fifty-four healthy individuals aged between 18 and 81 years underwent functional magnetic resonance imaging while they encoded and subsequently made new-old judgments on objects and positions. Region of interest (ROI) analysis of task related changes in the blood oxygen level dependent (BOLD) signal was performed in native space after correction for gender effects and individual differences in cerebral blood flow. The hippocampus, amygdala, and parahippocampal, perirhinal, entorhinal, and temporopolar cortices of right and left hemisphere were defined as ROIs. Aging had an adverse effect on memory performance that was similar for memorizing objects or positions. In left and right MTL, relatively greater activation for object stimuli was attenuated in older individuals. Age-related attenuation in content specificity was most prominent in the recognition stage. During recognition, the larger response to objects gradually decreased with age in all ROIs apart from left temporopolar and entorhinal cortex. An age-related attenuation was also present during encoding, but only in right parahippocampus and amygdala. Our results suggest that memory related processing in the MTL becomes gradually less sensitive to content during normal aging. PMID- 22054870 TI - A genome-wide scan for common variants affecting the rate of age-related cognitive decline. AB - Age-related cognitive decline is likely promoted by accumulated brain injury due to chronic conditions of aging, including neurodegenerative and vascular disease. Because common neuronal mechanisms may mediate the adaptation to diverse cerebral insults, we hypothesized that susceptibility for age-related cognitive decline may be due in part to a shared genetic network. We have therefore performed a genome-wide association study using a quantitative measure of global cognitive decline slope, based on repeated measures of 17 cognitive tests in 749 subjects from the Religious Orders Study. Top results were evaluated in 3 independent replication cohorts, consisting of 2279 additional subjects with repeated cognitive testing. As expected, we find that the Alzheimer's disease (AD) susceptibility locus, APOE, is strongly associated with rate of cognitive decline (P(DISC) = 5.6 * 10(-9); P(JOINT)= 3.7 * 10(-27)). We additionally discover a variant, rs10808746, which shows consistent effects in the replication cohorts and modestly improved evidence of association in the joint analysis (P(DISC) = 6.7 * 10(-5); P(REP) = 9.4 * 10(-3); P(JOINT) = 2.3 * 10(-5)). This variant influences the expression of 2 adjacent genes, PDE7A and MTFR1, which are potential regulators of inflammation and oxidative injury, respectively. Using aggregate measures of genetic risk, we find that known susceptibility loci for cardiovascular disease, type 2 diabetes, and inflammatory diseases are not significantly associated with cognitive decline in our cohort. Our results suggest that intermediate phenotypes, when coupled with larger sample sizes, may be a useful tool to dissect susceptibility loci for age-related cognitive decline and uncover shared molecular pathways with a role in neuronal injury. PMID- 22054873 TI - A difference between day and night: protein intake improves after the transition from conventional to frequent nocturnal home hemodialysis. AB - BACKGROUND: Malnutrition is an important cause of the excessive morbidity and mortality rate of dialysis patients. Frequent nocturnal home hemodialysis (NHHD) has many benefits compared with conventional thrice-weekly hemodialysis (CHD), due to the virtual absence of dietary restrictions and a much higher overall dialysis efficiency. In this observational study, we investigated whether these benefits of NHHD translate into an improved nutritional intake, with a special emphasis on protein intake. METHODS: We prospectively assessed the effect of the transition of CHD to NHHD on nutritional intake (5-day dietary intake journal), normalized protein catabolic rate, and anthropometric parameters in 15 consecutive patients who started NHHD in our center between 2004 and 2009 and completed at least 8 months of follow-up. Data were collected before the transition from CHD to NHHD and 4 and 8 months after the transition. RESULTS: Protein intake, as measured by both dietary intake journal and normalized protein catabolic rate, increased significantly after the transition from CHD to NHHD. Accordingly, phosphate intake increased significantly; however, serum phosphate levels did not increase, despite negligible phosphate binder use during NHHD. Body mass index and upper arm muscle circumference did not change significantly. CONCLUSION: The transition from CHD to NHHD has a positive effect on nutritional intake, in particular, protein intake. NHHD should be considered in malnourished patients on CHD. PMID- 22054874 TI - Leptin, insulin resistance, and metabolic changes 5 years after renal transplantation. AB - OBJECTIVE: To evaluate leptin, insulin resistance (IR), and changes in body composition and lipid profile within 5 years after renal transplantation. DESIGN: Longitudinal study. SETTING: Hospital de Clinicas de Porto Alegre/RS, Brazil. SUBJECTS: Thirty-two renal transplant recipients were followed up for 5 years after transplantation. METHODS: Data were collected at transplantation time (T1) and after 3 months (T2), 1 year (T3), and 5 years (T4). Leptin serum levels, IR assessed by homeostasis model assessment (HOMA) index, lipid profile, and anthropometric measurements were analyzed. Data were compared with a control group at baseline. RESULTS: At T1, pretransplant patients had leptin levels (ng/mL) (11.9 [9.2 to 25.2]) higher than the control group (7.7 [5.2 to 9.9]; P < .0001). After transplantation, levels decreased at T2 and T3, but increased at T4 to values similar to those seen at T1 (T4: 9.2 [5.7 to 21]; P = 1). HOMA also decreased at T2, but increased at T4 to identical levels (T1: 2.1 [1.63 to 2.23], T4: 2.1 [1.6 to 2.85]; P = 1). No significant changes in body fat percentage (BF%) were observed; however, the arm muscle circumference increased significantly at T4 (P < .0001). At T2, total cholesterol, triglycerides, and low density lipoprotein cholesterol increased, whereas at T4, lipid profile moved toward T1 levels. By linear regression analysis, gender, BF%, and HOMA were independent predictors of leptin levels. A trend toward higher body mass index was observed in woman who also presented higher leptin and lower HOMA levels. CONCLUSION: Leptin levels and HOMA decrease in the immediate posttransplant period and remain reduced for at least 1 year. Five years post transplantation, leptin, IR, BF%, and lipids have a profile similar to those in the pretransplant period. This metabolic profile is possibly associated with the elevated incidence of cardiovascular diseases observed in the late posttransplant period. PMID- 22054875 TI - Evaluation of mechanical allodynia in an animal immobilization model using the von frey method. AB - OBJECTIVE: The purpose of this study was to evaluate the mechanical allodynia in animals after immobilization and chiropractic manipulation using the Activator instrument (Activator Methods International, Phoenix, Ariz) through the Von Frey test in an animal model that had its hind limb immobilized as a form to induce mechanical allodynia. METHOD: Eighteen adult male Wistar rats were used and divided into 3 groups: control group (C) (n = 6) that was not immobilized; immobilized group (I) (n = 6) that had its right hind limb immobilized; immobilized and adjusted group (IAA) (n = 6) that had its right hind limb immobilized and received chiropractic manipulation after. The mechanical allodynia was induced through the right hind limb immobilization. At the end of the immobilization period, the first Von Frey test was performed, and after that, 6 chiropractic manipulations on the tibial tubercle were made using the Activator instrument. After the manipulation period, Von Frey test was performed again. RESULTS: It was observed that after the immobilization period, groups I and IAA had an exacerbation of mechanical allodynia when compared with group C (P < .001) and that after the manipulation, group IAA had a reversion of these values (P < .001), whereas group I kept a low pain threshold when compared with group C (P < .001). CONCLUSION: This study demonstrates that immobilization during 4 weeks was sufficient to promote mechanical allodynia. Considering the chiropractic manipulation using the Activator instrument, it was observed that group IAA had decreased levels of mechanical allodynia, obtaining similar values to group C. PMID- 22054877 TI - Preventing lung cancer by treating tobacco dependence. AB - Tobacco use is a chronic medical disorder. Providing evidence-based treatment of tobacco-dependent patients is a challenge, and a team approach provides an efficient treatment model. Tobacco treatment specialists could expand the collective tobacco treatment expertise in the medical setting. Effective tobacco dependence treatment frequently requires tailoring and intensifying of interventions to meet the needs of the individual patient. Stopping smoking reduces the risk of lung cancer and many other cancers, cardiovascular disease, stroke, peripheral vascular disease. Treating tobacco dependence is one of the most cost-effective therapies in medicine and it deserves adequate reimbursement for it to be more widely available. PMID- 22054878 TI - Screening for lung cancer. AB - The National Lung Screening Study has demonstrated that screening with low-dose spiral computed tomography results in fewer deaths from lung cancer compared with screening with chest radiography (CXR). Previous trials of screening with CXR and sputum cytology failed to exhibit fewer deaths compared with no screening intervention. Early computed tomography (CT) studies showed promise for CT to be a more sensitive test, yet were unable to demonstrate sufficient evidence of efficacy. This review examines the problem of early lung cancer detection, the issues presented by screening, and results of past and recent studies of lung cancer screening. PMID- 22054876 TI - Lung cancer: epidemiology, etiology, and prevention. AB - Lung cancer is the leading cause of cancer death in the United States and around the world. A vast majority of lung cancer deaths are attributable to cigarette smoking, and curbing the rates of cigarette smoking is imperative. Understanding the epidemiology and causal factors of lung cancer can provide additional foundation for disease prevention. This article focuses on modifiable risk factors, including tobacco smoking, occupational carcinogens, diet, and ionizing radiation. It also discusses briefly the molecular and genetic aspects of lung carcinogenesis. PMID- 22054879 TI - Pathology of lung cancer. AB - This article reviews current concepts in pathologic classification of lung cancer based on the 2004 World Health Organization classification of lung tumors and the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification of lung adenocarcinoma. Preinvasive lesions are discussed. The major changes in lung disease diagnosis affected by the IASLC/ATS/ERS classification are presented. For adenocarcinomas diagnosed in small biopsies, specific terminology and diagnostic criteria are proposed along with recommendations for strategic management of tissue and EGFR mutation testing in patients with advanced adenocarcinoma. Histologic criteria are also presented for other tumors. PMID- 22054880 TI - Preinvasive lesions of the bronchus. AB - It has been proposed that invasive carcinoma of the bronchus develops through a transition from preinvasive lesions to overt malignancy. Newer diagnostic technologies have provided a more sensitive way to diagnose preinvasive lesions and a better understanding of the prevalence of such lesions. The natural history of preinvasive lesions has not been well defined; however, there is evidence that high-grade lesions are at a higher risk of progression to carcinoma. Molecular alterations have been described in preinvasive lesions and may help better predict which lesions will progress. Several noninvasive techniques are available for the treatment of high-grade lesions. PMID- 22054882 TI - The revised stage classification system for primary lung cancer. AB - The revised stage classification system has improved the ability of clinicians to estimate prognosis based on specific staging determinations. Several important questions have been addressed, although many remain and will likely fuel the discussion for subsequent revisions. Perhaps more than previous revisions, the current iteration may cause confusion because of the emphasis on stage-specific treatment recommendations. However, prognosis is only 1 of the factors in a multidisciplinary treatment plan, and clinicians are encouraged to apply randomized trial data whenever possible. This global staging effort is testament to the progress that is possible through international collaboration. PMID- 22054883 TI - The use and misuse of positron emission tomography in lung cancer evaluation. AB - This article discusses the potential benefits and limitations of positron emission tomography (PET) for characterizing lung nodules, staging the mediastinum, identifying occult distant metastasis, determining prognosis and treatment response, guiding plans for radiation therapy, restaging during and after treatment, and selecting targets for tissue sampling. The key findings from the medical literature are presented regarding the capabilities and fallibilities of PET in lung cancer evaluation, including characterization of pulmonary nodules and staging in patients with known or suspected non-small-cell lung cancer. The discussion is limited to PET imaging with fluorodeoxyglucose. PMID- 22054884 TI - The pulmonologist's diagnostic and therapeutic interventions in lung cancer. AB - Diagnostic and therapeutic strategies for lung cancer have improved with advancing technology and the acquisition of the necessary skills by bronchoscopists to fully use these advanced techniques. The diagnostic yield for lung cancer has significantly increased with the advent of technologies such as endobronchial ultrasound, navigational systems, and improved imaging modalities. Similarly, the therapeutic benefit of bronchoscopy in advanced lung cancer has begun to be understood for its impact on quality and quantity of life. This article highlights the pulmonologists' diagnostic advances and therapeutic options, with an emphasis on outcomes. PMID- 22054885 TI - Functional evaluation before lung resection. AB - Lung cancer is the leading cause of cancer-related death worldwide, and lung resection remains the only curative approach. In the Western world, lung cancer is one of the main indications for lung resection, despite only 15% to 25% of all lung cancers being operable at the time of presentation. In most cases of operable lung cancer, a substantial part of functional lung tissue has to be resected, leading to a permanent loss of pulmonary function. Resection in patients with insufficient pulmonary reserves can result in permanent respiratory disability. This article reviews the current standards of preoperative assessment. PMID- 22054886 TI - Evaluation and treatment of high-risk patients with early-stage lung cancer. AB - Standard therapy for early-stage non-small cell lung cancer is lobectomy for patients who are able to tolerate such surgery. However, the risk of postoperative morbidity is not trivial, with a 30% to 40% incidence of postoperative complications and a 1% to 5% incidence of operative mortality. Some patients, though technically resectable, refuse surgery or are considered medically inoperable because of insufficient respiratory reserve, cardiovascular disease, or general frailty. This group is considered either "high risk" or "medically inoperable." PMID- 22054887 TI - Approach to the ground-glass nodule. AB - The detection of ground-glass opacity (GGO) is increasingly common. Sufficient data have been accumulated to formulate recommendations for observation, intervention, and treatment modalities. However, an understanding of many nuances and uncertainties in the available data is needed to avoid making management errors. This article discusses the range of possible entities, risk factors and characteristics that help make a presumptive clinical diagnosis, how often and for how long these should be followed when and how a biopsy should be done, how these lesions should be treated, and how multifocal GGOs should be approached. PMID- 22054888 TI - Additional pulmonary nodules in the patient with lung cancer: controversies and challenges. AB - The optimal management of an additional pulmonary nodule in a patient with a known primary lung cancer is unclear. Additional pulmonary nodules are often identified during pathologic evaluation after resection of a primary tumor rather than before surgery. Although correlating these pathologic data with preoperative information can be useful, their applicability to management and decision making is often limited. This article focuses on the malignant additional pulmonary nodule in the same lobe as the known primary tumor, in a different lobe in the same lung as the known primary tumor, and in the contralateral lung. PMID- 22054881 TI - Molecular biology of lung cancer: clinical implications. AB - Lung cancer is a heterogeneous disease clinically, biologically, histologically, and molecularly. Understanding the molecular causes of this heterogeneity, which might reflect changes occurring in different classes of epithelial cells or different molecular changes occurring in the same target lung epithelial cells, is the focus of current research. Identifying the genes and pathways involved, determining how they relate to the biological behavior of lung cancer, and their utility as diagnostic and therapeutic targets are important basic and translational research issues. This article reviews current information on the key molecular steps in lung cancer pathogenesis, their timing, and clinical implications. PMID- 22054890 TI - A decade of advances in treatment for advanced non-small cell lung cancer. AB - The last decade has heralded a paradigm shift in the evaluation and treatment of advanced non-small cell lung cancer (NSCLC). No longer are patients with NSCLC considered a homogeneous population treated in the same way; rather, clinical characteristics, histology, and an expanding array of molecular markers are increasingly being used to individualize therapy. Both histology and tumor epidermal growth factor receptor mutational status currently have firmly established roles in determining initial and salvage therapy for advanced NSCLC. Several other biomarkers are the focus of ongoing prospective randomized clinical trials customizing both traditional chemotherapy and newer molecularly targeted agents. PMID- 22054889 TI - A decade of advances in treatment of early-stage lung cancer. AB - Emerging from the past decade, there has been a diversification of options for the treatment of early-stage lung cancer. Video-assisted thoracoscopic surgery is now more widely performed, with oncologic outcomes equivalent to those with open thoracotomy. Although lobectomy remains the standard approach to surgical resection, lesser resections, such as segmentectomy and wedge resection, are considerations for some patients. Advances in surgical, radiation, and medical therapies continue to evolve. Future research questions will focus on comparing long-term outcomes with these modalities, including survival, as well as patient centered endpoints, such as quality of life. PMID- 22054891 TI - Current management of small cell lung cancer. AB - Confined to one side of the chest, limited stage small cell lung cancer is treated with a combination of chemotherapy and radiotherapy, yet has a long-term survival rate of only 15%. Extensive stage disease has initial response rates to chemotherapy exceeding 70%. However, the disease almost invariably progresses and becomes fatal. Many recent clinical trials have failed to show superiority of newer chemotherapeutics or targeted therapies compared with the standard chemotherapy backbone of platinum plus etoposide. Numerous promising targeted therapies and other agents are still in development. PMID- 22054895 TI - The use of electronic grading probes for the objective assessment of PSE and DFD in pork carcasses. AB - Three electronic grading probes, the Hennessy Grading Probe (GP-II), Fat-O-Meater (FOM) and Destron Pork Grader (PG-100) were assessed for their ability to detect the PSE/DFD conditions in pork. Carcasses were probed either at the time of grading (35, 45 or 60 min post mortem for the GP-II and PG-100, and 60 min post mortem for the FOM) or 24 h post mortem for all three probes. Probings were made between the 3rd and 4th last ribs, 7 cm lateral to the mid-line on the left side of the carcass. The relationship between the mean internal muscle reflectance, calculated by averaging all reflectance values less those recorded for the first and last 4 mm of muscle thickness, and the overall quality of boneless loins was used to assess the three probes. The overall quality of the boneless loins was subjectively assessed 24 h post mortem using a 5-point descriptive scale for paleness and structure in use in Canada since 1984 to describe the PSE/DFD conditions in pork. The relationships between the mean internal muscle reflectance and the subjectively determined overall quality score were weakest at time of grading and strongest at 24h post mortem. The coefficients of correlation were as follows: at 35 min post mortem, GP-II: -0.23 and -0.23 for paleness and structure, respectively, PG-100: -0.01 and -0.24; at 45 min post mortem, GP-II: 0.30 and -0.29, PG-100: -0.01 and -0.22; at 60 min post mortem, GP-II: -0.42 and 0.37, FOM: -0.01 and -0.02, PG-100: -0.29 and -0.30; at 24h post mortem, GP-II: 0.68 and -0.58, FOM: -0.53 and -0.50, PG-100: -0.45 and -0.49. Our results strongly suggest that early post mortem reflectance measurements made with the GP II, FOM or PG-100 were of no value in detecting the PSE/DFD conditions in pork. Furthermore, despite relatively strong correlations between the mean internal muscle reflectance measured 24 h post mortem and the subjectively determined quality score, the extent of overlapping between quality scores in the distribution of the mean internal muscle reflectance within each quality score precluded the definition of unique reference values for each quality score. Consequently, the measurement of the mean internal muscle reflectance could not reliably distinguish the various Canadian quality standards used to identify PSE/DFD in pork. PMID- 22054896 TI - Estimating beef carcass composition using the speed of ultrasound. AB - The reciprocal of the speed of 2.25 MHz (nominal) ultrasound (RV) was measured at selected sites through the soft tissues of 72 beef carcasses from Friesian. Hereford and Hereford * Friesian bulls and steers at or within 1 h of stunning. The measurement sites were: through M. adductor horizontal to the caudal edge of the symphysis pubis (S2), through M. scalenus just cranial to the first rib (S3) and through M. longissimus thoracis between the tenth and eleventh ribs, approximately 6 cm from the midline (S4). The thickness of extractable lipid (d(f)) at each site was defined as the product betad, where beta was the volume fraction of extractable lipid and d was the tissue thickness. The thickness of lipid-free tissue (d(ff)) was defined as (d-d(f)) and beta was calculated from the ultrasonic measurements using an empirical linear relation between beta and RV. When cold, the intact sides were scored independently for fatness and conformation by two experienced judges according to the EAAP system and their mean scores determined. Sides were split at the level of the last rib and the depth of subcutaneous fat measured at 25%, 50% and 75% of the width of M. longissimus thoracis from the midline. The three ultrasonic characteristics (RV, d(f) and d(ff)) at each site, the mean fat depth and the mean fat and conformation scores were examined for correlation with % fat and % lean in the sides determined by complete physical dissection. The best predictors of % fat were mean d(f) at S3 and S4, mean d(f) at S2, S3 and S4 and mean EAAP fat score which were all of comparable precision (rsd, respectively, 2.07, 2.06 and 2.08). The best predictors of % muscle were mean d(f) at S3 and S4, mean d(f) at S2, S3 and S4 and mean RV at S2, S3 and S4 (rsd, respectively, 1.79, 1.79 and 1.90). The corresponding residual standard deviations for mean EAAP fat score and mean fat depth were 2.18 and 2.20. PMID- 22054892 TI - Gene therapy for lung neoplasms. AB - Both advanced-stage lung cancer and malignant pleural mesothelioma are associated with a poor prognosis. Advances in treatment regimens for both diseases have had only a modest effect on their progressive course. Gene therapy for thoracic malignancies represents a novel therapeutic approach and has been evaluated in several clinical trials. Strategies have included induction of apoptosis, tumor suppressor gene replacement, suicide gene expression, cytokine-based therapy, various vaccination approaches, and adoptive transfer of modified immune cells. This review considers the clinical results, limitations, and future directions of gene therapy trials for thoracic malignancies. PMID- 22054897 TI - Effects of electrical stimulation and temperature on beef quality and tenderness. AB - Beef carcasses were stimulated with either 50 or 500 V and exposed to three chilling temperatures during the first 3 to 9 h post mortem. Both high (HV) and low voltage (LV) electrical stimulation (ES) treatments improved lean maturity scores, lowered the pH values at 2 h through 12 h and reduced the time required for the ATP level to reach minimum values. Both HV-ES and LV-ES treatments influenced firmness, fragmentation and connective tissue (CT) residue as measured by sensory panel and reduced Instron shear value (ISV) of loin steaks. The 30 degrees C temperature treatment had an adverse effect while the 20 degrees C temperature treatment had a beneficial effect on ISV and panel ratings for firmness and CT residue. There was an interaction between conditioning treatments and ES for ISV and sensory panel traits. The LV-ES-20C treatment resulted in the lowest ISV and superior panel ratings; however, the LV-ES-30C treatment had ISV and sensory panel ratings that were similar to the NES-2C (control) group. PMID- 22054898 TI - Effect of low voltage electrical stimulation on the distribution of cathepsin D and the palatability of the Longissimus dorsi from Holstein veal calves fed a corn or barley diet. AB - Forty male Holstein veal calves (45 kg) were weaned on milk replacer given once or twice daily and fed either a corn or a barley diet until slaughter at 215 kg liveweight. Carcasses from half of the animals on each diet were assigned to low voltage electrical stimulation (LVES), the other half served as controls. LVES accelerated the pH drop of the meat (P<0.01) and resulted in a more rapid liberation of cathepsin D (P < 0.01) in the soluble fraction of the longissimus dorsi homogenate. Despite the faster liberation of cathepsin D, meat samples from the LVES group were tougher than those of controls (P < 0.01). Meat colour measured by reflectance was not affected by the post-mortem treatments but ageing for six days significantly decreased the reflectance measurements (P < 0.01). The meat flavor was more pronounced for controls and for barley fed animals (P < 0.01). SDS-polyacrylamide gel electrophoresis of the myofibrillar proteins demonstrated that meat ageing favored the degradation of troponin-T (TN-T) and the appearance of a new banding pattern in the 25-35 kdalton region. Compared with controls ES had a tendency to decrease the rate of degradation of TN-T although no difference in the banding patterns could be observed after 6 days of ageing. PMID- 22054899 TI - Influence of an extract of liver on colour and shelf stability of sliced bologna. AB - The influence of the substances present in an extract of liver on the characteristics of bologna sausage was studied in sliced, vacuum-packaged bologna stored under refrigeration for 70 days in darkness or exposed to light (180 +/- 10ft-c). The extract replaced 0, 50 or 100% of the water added during formulation. The characteristics studied were colour intensity and stability, residual nitrite content, and oxidative rancidity. Colour fading was nearly non existent in the batches stored in darkness but was more pronounced in those exposed to light, in which the rate of fading was inversely dependent upon the proportion of extract added. Nitrite loss over the storage period followed a first-order kinetic equation and was dependent upon both liver extract concentration (higher at higher extract levels) and the storage conditions (more pronounced in the batches exposed to light). The changes in the residual nitrite concentration could be attributed to its colour stabilizing action. While the 2 thiobarbituric acid (TBA) index tended to be higher at higher concentrations of liver extract, the increases were not substantial and were not dependent upon the storage period or illumination. Rancidity was not a limiting factor in the refrigerated storage of the product. PMID- 22054900 TI - A note on the nature of the haematin pigments present in freeze dried and cooked beef. AB - Analysis of the reflectance spectra of beef samples treated to contain all the haemoproteins in one pigment form indicated that little or no change in the haematin environment occurs on freeze drying fresh, oxymyoglobin-rich meat or cooked meat. Dehydration of metmyoglobin in meat results in the water molecule at the sixth coordination site being replaced by a protein-bound ligand. On rehydration, this ligand may be replaced by water to reform metmyoglobin, but the degree of conversion depends on the rate of rehydration. The spectral similarity between cooked and freeze dried, oxidised meat indicates that the haematin environments are similar. It is suggested that in these meats the predominant pigments are di-imidazole complexes. PMID- 22054901 TI - Letter to the editor. PMID- 22054902 TI - Effect of pelvic obliquity on the orientation of the acetabular component in total hip arthroplasty. AB - In infrapelvic obliquity, coronal pelvic malrotation entails a change in the spatial location of the bony acetabulum. In the present study, 77 patients presented with infrapelvic obliquity with types 1 and 2 hip pathologies in which the pelvis is lower and higher, respectively, on the short-leg side. The 2 types were classified into 3 subtypes (A, B, and C) according to the severity of the pelvic obliquity (0 degrees -3 degrees , 3 degrees -6 degrees , and >6 degrees ). Angles of inclination of pelvic obliquity postoperatively, anteversions, and inclinations (abduction angle) for acetabular components were measured after total hip arthroplasty. Increased inclination (mean, 8.79 degrees ) was observed in type 1C, where the angle of inclination to pelvic obliquity postoperatively was minimally corrected. This increase may lead to cup instability. Rebalancing the pelvis in these cases with preoperative skeletal traction and/or sufficient release of hip contractures may be necessary. A correction of the mean inclination of the cup by 8.79 degrees is required. PMID- 22054903 TI - Improvements in knee range and symptomatic and functional behavior after knee arthroplasty based on preoperative restriction in range. AB - Recovery of knee range and Oxford Knee Score post knee arthroplasty based on preoperative knee range is described. A total of 191 patients recruited across 5 hospitals were assessed preoperatively, at 8 weeks postoperatively and 1 year. Preoperative knee range was categorized into "low" (<= 109), "moderate" (> 109 to <= 120), and "high" (> 120 degrees ) flexion and "normal" (+/- -5) and "restricted" (> +5 degrees ) terminal extension. Recovery was analyzed using MIXED modeling procedures. The low-flexion group gained flexion across time. The moderate-flexion and high-flexion groups lost flexion initially then recovered, but 1-year flexion remained lower than preoperative values. The restricted terminal extension group gained extension across time. The normal terminal extension group lost extension initially then recovered to preoperative values at 1 year. Recovery in Oxford score was independent of preoperative knee range limitation. Improvement in knee range postoperatively, but not self-reported behavior, is highly dependent on the initial restriction in range. PMID- 22054904 TI - Unipolar vs bipolar hemostasis in total knee arthroplasty: a prospective randomized trial. AB - The purpose of this study was to investigate whether unipolar or bipolar hemostasis is more effective in reducing blood loss associated with primary total knee arthroplasty. We randomized 113 consecutive patients undergoing primary total knee arthroplasty into unipolar and bipolar hemostasis treatment groups. The mean postoperative drain output in the unipolar group was 776.5 mL compared with 778.7 mL and was not statistically significant (P = .97). There were no statistically significant differences in postoperative day 1 through 3 hemoglobin level (P = .2-.6) or hematocrit (P = .17-.46) values. The transfusion requirement in the unipolar group was 36% and 40% in the bipolar group (P = .67). Use of bipolar sealer compared with standard unipolar electrocauterization showed no significant difference in postoperative drain output, postoperative hemoglobin level and hematocrit values, or transfusion requirements. PMID- 22054905 TI - Diabetes mellitus, hemoglobin A1C, and the incidence of total joint arthroplasty infection. AB - Patients with diabetes have a higher incidence of infection after total joint arthroplasty (TJA) than patients without diabetes. Hemoglobin A1c (HbA1c) levels are a marker for blood glucose control in diabetic patients. A total of 3468 patients underwent 4241 primary or revision total hip arthroplasty or total knee arthroplasty at one institution. Hemoglobin A1c levels were examined to evaluate if there was a correlation between the control of HbA1c and infection after TJA. There were a total of 46 infections (28 deep and 18 superficial [9 cellulitis and 9 operative abscesses]). Twelve (3.43%) occurred in diabetic patients (n = 350; 8.3%) and 34 (0.87%) in nondiabetic patients (n = 3891; 91.7%) (P < .001). There were 9 deep (2.6%) infections in diabetic patients and 19 (0.49%) in nondiabetic patients. In noninfected, diabetic patients, HbA1c level ranged from 4.7% to 15.1% (mean, 6.92%). In infected diabetic patients, HbA1c level ranged from 5.1% to 11.7% (mean, 7.2%) (P < .445). The average HbA1c level in patients with diabetes was 6.93%. Diabetic patients have a significantly higher risk for infection after TJA. Hemoglobin A1c levels are not reliable for predicting the risk of infection after TJA. PMID- 22054906 TI - The effect of hip position on the length of trochanteric muscles: potential implications for early postoperative management of hip arthroplasty. AB - We investigated the effect several lower limb positions have on muscles that are detached to perform hip arthroplasty through posterior and lateral approaches. We used string models and computer navigation to measure the length changes in these muscles throughout hip movements in the anatomical planes and while simulating several sitting and lying postures. Piriformis and the obturators were shortened by sitting and lying postures when the femur was externally rotated and abducted; the clinical implication being that such postures have the potential to best protect their repair after a posterior approach. The anterior part of gluteus medius was lengthened with femoral external rotation. This lengthening was prevented, and therefore, theoretically, the gluteus medius repair protected after a lateral approach, by neutral or internal femoral rotation. PMID- 22054907 TI - Law and cancer at the end of life: the problem of nomoigenic harms and the five desiderata of death law. AB - Good laws are a necessary, but not a sufficient, condition for the provision of good health care. At the end of life, there is a need for laws that foster and encourage the best possible outcomes for patients, their families and healthcare professionals. This article proposes five desiderata for laws at the end of life. It uses the emerging Australian jurisprudence of end-of-life decision making to test and examine the desiderata. The article also proposes that poorly drafted and confusing laws may have a deleterious effect on patient care. These nomoigenic (law-caused) harms can be avoided by adherence to the five desiderata of death law. PMID- 22054908 TI - Implications of international law for the treatment of cancer: the Single Convention on Narcotic Drugs and the TRIPS Agreement. AB - The development, manufacture, trade and distribution of medicines all take place within a web of international legal obligations that states have accepted under a range of multilateral, plurilateral and bilateral agreements. International law can operate either to facilitate or hinder access, depending on how it is developed and implemented. This article examines two areas of international law that are relevant to cancer treatment: the international drug control system, which regulates opioid analgesics; and the World Trade Organization's Trade Related Aspects of Intellectual Property Agreement. This article outlines recent developments in relation to both, including in the activities of the Vienna-based agencies that collectively oversee the implementation of the Single Convention on Narcotic Drugs, and in the negotiation of the recent United Nations General Assembly Political Declaration on Non-communicable Diseases. While underlining the importance of law, this article notes that battles over law should not distract from the importance of other essential efforts to enhance access to medicines within the context of the strengthening of health systems. PMID- 22054909 TI - Multiple associated injuries are common with spine fractures during war. AB - BACKGROUND CONTEXT: The nature of concomitant injuries associated with spine fractures in American military personnel engaged in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) has been poorly documented in the literature. PURPOSE: To characterize the incidence and epidemiology of associated injuries (AIs) in American military personnel with spine fractures sustained during OEF and OIF from 2001 to 2009. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: American military personnel who were injured in a combat zone and whose medical data were abstracted in the Joint Theater Trauma Registry (JTTR). OUTCOME MEASURES: Not applicable. METHODS: The JTTR was queried using International Statistical Classification of Disease, Ninth Revision codes to identify all individuals who sustained spine injuries in OEF or OIF from October 2001 to December 2009. Medical records of all identified service members were abstracted to ensure accuracy and avoid duplication. Demographic information, including sex, age, and military rank, were obtained for all patients. Information regarding fracture type, spine region, mechanism of injury, and the presence of AIs was collected for all patients. RESULTS: Seventy-eight percent of patients with a spine fracture sustained at least one AI, with an average of 3.4 AIs per patient. Musculoskeletal injuries were most common, followed by chest, abdomen, and traumatic brain injuries. Most patients were injured by an explosive mechanism (62%). Head and face traumas were more common with cervical fractures, chest with thoracic injuries, and abdominopelvic injuries with lumbosacral fractures. Pelvis and acetabulum fractures were common after helicopter crashes, tibia/fibula injuries after explosions, thoracoabdominal injuries after gunshot wounds, and traumatic brain injuries after falls. Most patients (76%) sustained multiple spine fractures. CONCLUSION: Spine fractures sustained in OEF and OIF have high rates of AIs. Musculoskeletal AIs are the most common, but visceral injuries adjacent to the spine fracture frequently occur. Multiple spine injuries are more prevalent after military trauma. PMID- 22054910 TI - The chaperone-histone partnership: for the greater good of histone traffic and chromatin plasticity. AB - Histones are highly positively charged proteins that wrap our genome. Their surface properties also make them prone to nonspecific interactions and aggregation. A class of proteins known as histone chaperones is dedicated to safeguard histones by aiding their proper incorporation into nucleosomes. Histone chaperones facilitate ordered nucleosome assembly and disassembly reactions through the formation of semi-stable histone-chaperone intermediates without requiring ATP, but merely providing a complementary protein surface for histones to dynamically interact with. Recurrent 'chaperoning' mechanisms involve the masking of the histone's positive charge and the direct blocking of crucial histone surface sites, including those required for H3-H4 tetramerization or the binding of nucleosomal DNA. This shielding prevents histones from engaging in premature or unwanted interactions with nucleic acids and other cellular components. In this review, we analyze recent structural studies on chaperone histone interactions and discuss the implications of this vital partnership for nucleosome assembly and disassembly pathways. PMID- 22054911 TI - Mechanism of W(CO)6 sonolysis in diphenylmethane. AB - The present work analyses the mechanism of W(2)C/C nanocomposite formation during sonolysis of W(CO)(6) in diphenylmethane (DPhM) solutions. Carbon supported WC(x) nanoparticles attract much interest as an alternative fuel cell electrocatalysts. Sonolysis of neat DPhM under the effect of 20 kHz power ultrasound in argon at 80 degrees C yields a sonopolymer as a solid product and acetylene, hydrogen, methane, diacetylene and benzene as gaseous products. Diacetylene is formed due to the secondary sonochemical dimerisation of acetylene obtained at the primary stage of DPhM sonolysis. FTIR and MU-Raman studies show that the sonopolymer consists of a mixture of some polymeric partially oxidized aromatic species, and disordered carbon. Sonolysis of W(CO)(6) in diphenylmethane solutions follows the first order kinetics. This process yields monodispersed 2-3 nm X-ray amorphous WC(x) nanoparticles embedded in amorphous sonopolymer. The annealing of air sensitive as-prepared solids in an inert atmosphere at 600 degrees C causes formation of stable W(2)C/C nanocomposite with W(2)C average particle size in the range of 4-7 nm and hexagonal carbon fine particles with the average size of 30 40 nm. Kinetic study revealed that tungsten carbide is formed inside the cavitation bubble due to the reaction of tungsten nanoparticles originated from primary sonolysis of W(CO)(6) with acetylene produced as a result of diphenylmethane sonochemical degradation. PMID- 22054912 TI - UAE, MAE, SFE-CO2 and classical methods for the extraction of Mitragyna speciosa leaves. AB - Mitragyna speciosa, a tropical plant indigenous to Southeast Asia, is well known for its psychoactive properties. Its leaves are traditionally chewed by Thai and Malaysian farmers and manual labourers as it causes a numbing, stimulating effect. The present study aims to evaluate alkaloid yield and composition in the leaf extracts. For this purpose we have compared several non-conventional extraction techniques with classic procedures (room temperature or under heating). Dried M. speciosa leaves belonging to three batches of different origin (from Thailand, Malaysia and Indonesia) were extracted using ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and supercritical carbon dioxide extraction SFE-CO(2), using methanol, ethanol, water and binary mixtures. The extracts were compared using an HPLC/ESI-MS analysis of mitragynine and four other related alkaloids which were present in the alkaloid fraction. The extraction technique influences both the raw product yield and the relative alkaloid content of M. speciosa leaves. Of the several methods tested, MAE in a closed vessel at 110 degrees C (60 W, methanol/water 1:1) gave the highest alkaloid fraction amount, while UAE with an immersion horn at 25 degrees C (21.4 kHz, 50 W, methanol) showed the best yield for mitragynine. This work may prove to be a useful contribution to forensic, toxicological and pharmacognosy studies. Although the potential applications of M. speciosa alkaloids clearly need further investigation, these results may facilitate the scaling-up of their extraction. PMID- 22054913 TI - Patients with atrial fibrillation in a primary care setting: Val-FAAP study. AB - OBJECTIVE: To assess the clinical characteristics of patients with atrial fibrillation in the primary care setting. METHODS: This was a 2-phase, cross sectional, multicenter study: phase A assessed the proportion of atrial fibrillation patients assisted in primary care over 5 days; phase B analyzed atrial fibrillation patients' clinical characteristics and management. RESULTS: In phase A, 119 526 subjects (age 52.9 [15.2] years; 40.9% male) received primary care in participating centers; 6.1% had atrial fibrillation. This proportion increased with age, hypertension, and male sex. In phase B, we analyzed 3287 atrial fibrillation patients (age 71.9 [10.1] years; 52.3% male). Risk factors were hypertension (92.6%), hypercholesterolemia (70.6%), related cardiovascular disease, heart failure (21.3%), and ischemic heart disease (20.9%). Permanent atrial fibrillation was the most frequent type of atrial fibrillation (45.3%). Age and cardiac and renal diseases were related to permanent atrial fibrillation development. Although more than two-thirds of patients had a CHADS(2) score >=2, about one-third of them were not taking anticoagulants; by contrast, 46.8% of patients with CHADS(2)=0 were taking oral anticoagulants. CONCLUSIONS: In primary care, 6.1% of patients had atrial fibrillation. Patients with atrial fibrillation had high comorbidity. Anticoagulant treatment is far from optimal for atrial fibrillation patients in primary care. PMID- 22054914 TI - Bone marrow gold. PMID- 22054915 TI - The effectiveness of a computer-tailored smoking cessation intervention for participants in lung cancer screening: a randomised controlled trial. AB - BACKGROUND: Lung cancer screening might be a teachable moment for smoking cessation intervention. The objective was to investigate whether a tailored self help smoking cessation intervention is more effective in inducing smoking cessation compared to a standard brochure in male smokers who participate in the Dutch-Belgian randomised controlled lung cancer screening trial (NELSON trial). METHODS: Two random samples of male smokers who had received either a standard brochure (n=642) or a tailoring questionnaire for computer-tailored smoking cessation information (n=642) were sent a questionnaire to measure smoking behaviour two years after randomisation. RESULTS: Twenty-three percent of the male smokers in the tailored information group returned a completed tailoring questionnaire and thus received the tailored advice. The prolonged smoking abstinence was slightly, but not statistically significant, lower amongst those randomised in the tailored information group (12.5%) compared with the brochure group (15.6%) (OR=0.77 (95%-CI: 0.56-1.06). The level of education and intention to quit smoking significantly predicted smoking cessation at follow-up (p<0.05). The majority of the respondents did not recall whether and which smoking cessation intervention they had received at randomisation after 2-years of follow up. CONCLUSION: The current study showed no advantage of tailored smoking cessation information over standard self-help information amongst male smokers with a long term smoking history who participate in a lung cancer screening trial after two years of follow-up. However, the low percentage participants who actually received the tailored advice limited the ability to find an advantage. PMID- 22054916 TI - New data, new paradigms for treating patients with prostate cancer: introduction. PMID- 22054917 TI - Focusing on testosterone. AB - Since Huggins and Hodges first established testosterone as the principal androgenic hormone responsible for the growth of prostate cancer in 1941, lowering the circulating testosterone to surgical castration levels (<50 ng/dL) has been a fundamental strategy for prostate cancer therapy. Until the 1980s, surgical castration (bilateral orchiectomy) and medical castration using estrogen (diethylstilbestrol) were the primary methods of testosterone suppression. However, during the past 30 years, newer agents that lower serum testosterone even more effectively have been approved and the indications for use of these newer agents re-evaluated. PMID- 22054918 TI - Indications and practice with androgen deprivation therapy. AB - The Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) is an ongoing longitudinal observational study of current trends in prostate cancer staging and treatment across a spectrum of different treatment facilities in the United States. To date, the study has documented 2 principal findings: (a) a large variation exists in the treatment choices applied to similar patient presentations across the range of facility type, size, and geographic location in the United States; and (b) although it does not seem to make much difference in mortality outcomes which approach--hormonal therapy, radiotherapy, or surgery--is applied to men at low or intermediate risk, a survival benefit exists with surgery for men at high risk. PMID- 22054919 TI - Targeting the androgen receptor--theory and practice. AB - Intensive investigation during the past 2 decades has led to an improved knowledge of the biology of the androgen receptor and a better understanding of how to assess for disease progression and the apparent existence of castrate resistant prostate cancer. The result has been the clinical development of a new generation of hormonal therapy agents for achieving the androgen deprivation necessary to achieve castrate levels of circulating testosterone. It has also resulted in the realization that it is probably time to move away from using terms such as "hormone-refractory" and "androgen-independent" prostate cancer, given the clear evidence that significant, effective, ongoing suppression of testosterone, using better drugs and better assays, will continue to be the standard of care. PMID- 22054920 TI - Traditional approaches to androgen deprivation therapy. AB - For most of the past 25 years, 1 of the favored approaches to treating prostate cancer has been the suppression of circulating testosterone with luteinizing hormone-releasing hormone (LHRH) agonists. LHRH agonists produce a downregulation of LHRH receptors and an uncoupling of the LHRH signal transduction mechanism. This leads to a marked reduction in the secretion of bioactive hormones stimulating testosterone production and eventual induction of a reversible, but transient and incomplete, state known as "selective medical hypophysectomy." The treatment with LHRH agonists has proved effective in many settings; however, the dosage and timing strategies depend critically on the patient's disease risk and progression. More recent investigations have suggested that a newer, quicker acting, pure gonadotropin-releasing hormone antagonist might be a preferable treatment approach. It remains a fundamental truth, however, that hormonal therapy is both overused and more toxic than generally appreciated. Therefore, a complete understanding of the indications and applications of this approach is essential for the practice of evidence-based medicine. PMID- 22054921 TI - New data, new paradigms for treating prostate cancer patients--VI: novel hormonal therapy approaches. AB - Until the 1980s, testosterone suppression for men with advanced prostate cancer was managed surgically, with bilateral orchiectomy, or medically, with diethylstilbestrol, a drug that was associated with a problematic side effect profile. Beginning in the mid-1980s, the U.S. Food and Drug Administration approved the first luteinizing hormone-releasing hormone agonists, which proved effective for suppressing circulating testosterone levels and led to a significant shift away from surgical castration to medical management during the past 25 years. The luteinizing hormone-releasing hormone agonists resulted in a periodic return of noncastrate testosterone levels once the receptor desensitization attenuated and the effect of androgen agonism resumed. Therefore, the introduction of an androgen receptor antagonist (gonadotropin-releasing hormone antagonist) appeared, conceptually at least, to be a preferable alternative. The first such agent, degarelix, has proved to provide rapid testosterone suppression without the initial testosterone surge associated with luteinizing hormone-releasing hormone agonists. Other new agents in early development include a selective and irreversible inhibitor of CYP17, abiraterone, which has shown success in patients with castration-resistant metastatic prostate cancer, and MDV3100, a novel small molecule that acts as an oral nonsteroidal antiandrogen agent. In sum, these latest agents might lead to a paradigm shift in the treatment of patients with advanced prostate cancer; however, additional studies are required to clarify the many questions that remain regarding the optimal use and sequence of these agents. PMID- 22054922 TI - New data, new paradigms for treating patients with prostate cancer. Conclusion. PMID- 22054923 TI - Protein SUMOylation in spine structure and function. AB - The active regulation of spine structure and function is of fundamental importance for information storage in the brain. Many proteins involved in spine development and activity-dependent remodelling are potential or validated substrates for modification by the Small Ubiquitin-like Modifier (SUMO). The functional consequences of neuronal protein SUMOylation appear diverse and, in many cases, have not yet been determined. However, for several proteins SUMOylation has been shown to be a key regulator, which has a profound impact on spine dynamics and protein trafficking and function. Here we provide an overview of neuronal SUMOylation and discuss how greater understanding of this relatively recently discovered posttranslational modification will provide insight into the complexity of protein interactions that control synaptic activity and dysfunction. PMID- 22054924 TI - Pain and itch: insights into the neural circuits of aversive somatosensation in health and disease. AB - Although pain and itch are distinct sensations, most noxious chemicals are not very specific to one sensation over the other, and recent discoveries are revealing that Trp channels function as transducers for both. A key difference between these sensations is that itch is initiated by irritation of the skin, whereas pain can be elicited from almost anywhere in the body; thus, itch may be encoded by the selective activation of specific subsets of neurons that are tuned to detect harmful stimuli at the surface and have specialized central connectivity that is specific to itch. Within the spinal cord, cross-modal inhibition between pain and itch may help sharpen the distinction between these sensations. Moreover, this idea that somatosensory modalities inhibit one another may be generalizable to other somatosensory subtypes, such as cold and hot. Importantly, just as there are inhibitory circuits in the dorsal horn that mediate cross-inhibition between modalities, it appears that there are also excitatory connections that can be unmasked upon injury or in disease, leading to abnormally elevated pain states such as allodynia. We are now beginning to understand some of this dorsal horn circuitry, and these discoveries are proving to be relevant for pathological conditions of chronic pain and itch. PMID- 22054925 TI - Chemosensory-induced motor behaviors in fish. AB - Chemical sensory signals play a crucial role in eliciting motor behaviors. We now review the different motor behaviors induced by chemosensory stimuli in fish as well as their neural substrate. A great deal of research has focused on migratory, reproductive, foraging, and escape behaviors but it is only recently that the molecules mediating these chemotactic responses have become well characterized. Chemotactic responses are mediated by three sensory systems: olfactory, gustatory, and diffuse chemosensory. The olfactory sensory neuron responses to chemicals are now better understood. In addition, the olfactory projections to the central nervous system were recently shown to display an odotopic organization in the forebrain. Moreover, a specific downward projection underlying motor responses to olfactory inputs was recently described. PMID- 22054926 TI - Post-mortem evolution of rheological properties of the myofibrillar structure. AB - The post-mortem evolution of the rheological behaviour of beef muscle has been studied with the SATA compressive device. The resistance and elasticity of the muscle tissue, measured at low strain, refer to the myofibrillar structure and provide an indication of the advance of the rigor maturation process. These parameters have been used to quantify the electrical stimulation effect on Longissimus dorsi and Semi-membranosus muscles. An empirical model is proposed for the post-mortem evolution of the resistance and provides three parameters-the initial rate of rigor onset, the time of rigor and the residual stress after ageing. On the other hand, parameters obtained at high strain refer mainly to the connective tissue. The particularly high stress developed by the pre-rigor muscle, however, is presumed to be associated with the myofibrillar component. PMID- 22054927 TI - Cholesterol oxides in processed meats. AB - Methods for the extraction of cholesterol oxides from meats were studied. A dry column technique for the extraction of sterols was found to be more rapid and convenient than conventional chloroform-methanol extraction. An overall yield of 32.0% and 23.6% for radiolabelled cholesterol and cholesterol oxides, respectively, was obtained after dry column extraction, saponification and chromatography on a silica arrestant column, Florisil(r)-AgNO(3) column and silica Sep-Pak(r) column. The overall extraction efficiency of ten meat samples was 22.3 +/- 1.7 %. Cholesterol oxides present in measurable amounts included 5 cholesten-3beta, 19-diol, 5-cholesten-3beta-ol-22-one, the alpha and beta epimers of 5-cholesten-3beta, 7-diol and cholestan-3 beta, 5alpha, 6beta-triol in some of the meat samples analyzed, but, for the majority of samples, no detectable amounts of known cholesterol oxides were found. Most of the meats, however, contained unidentified components that are non-polar with respect to cholesterol. PMID- 22054928 TI - Effect of zeranol on bull muscle fibre composition. AB - Two trials are reported in which bulls were implanted with zeranol and slaughtered at 18 months. There was no significant change in carcass weight due to zeranol in either trial. Samples of the longissimus dorsi (LD) and splenius (Sp) were cross-cryosectioned, stained for myofibrillar ATPase and examined by conventional light microscopy. The stain resolved three fibre types: I, slow contracting with an oxidative metabolism, IIA, fast-oxidative-glycolytic and IIB, fast-glycolytic. In the LD from treated bulls, the occurrence of IIB fibres was increased, apparently at the expense of IIA fibres, as the occurrence of I fibres was unchanged. These occurrence changes parallelled previously reported effects of castration. Changes in Sp were less dramatic. In one trial IIB fibres were absent from all Sp muscles, but, in the other, some of the Sp muscles from treated animals contained these fibres whereas they were absent from the Sp of the control group. If the changes in fibre type occurrence due to zeranol extend to skeletal muscles other than LD and Sp, there is likely to be a subtle change in the musculature's metabolism. Fibre areas were largely unaffected by zeranol. In this respect zeranol did not mimic castration. PMID- 22054929 TI - Post-natal changes in some histochemical and enzymatic characteristics of three pig muscles. AB - Post-natal changes in histoenzymatic and enzymatic characteristics were studied in porcine longissimus, psoas major and tibialis cranialis muscles. The experiment was carried out on thirty-five female large White pigs: fifteen were slaughtered between birth and 120 kg body weight (BW) and twenty at the market liveweight of 100 kg. The relative growth of each of the three muscles in relation to BW appeared to be monophasic, the allometric growth rates differed significantly between muscles: 1.21, 1.08 and 0.97, respectively. Myofibers were classified according to their contractile and metabolic properties as betaR, alphaR and alphaW fibers. In the three muscles, the percentage of beta fibers increased from birth up to 2 months of age and little change occurred thereafter. Glycolytic fibers were detectable only from about one month onwards. Their percentage then increased rapidly up to 30-50 kg BW to reach 60%, 30% and 12% in longissimus, psoas major and tibialis cranialis muscles, respectively. Thereafter, these values only changed slightly. This histoenzymatic differentiation led to the typical type grouping found in pigs. Throughout the period studied, the cross-sectional area of the myofibers increased with some differences according to fiber type and muscle. Lactate dehydrogenase (LDH) specific activity was similar in the three muscles at birth and then increased rapidly up to 4-5kg BW (15-20 days of age), although to a greater extent in the future glycolytic muscle (longissimus) This increase then abruptly slowed down. The period between 15 and 20 days of age corresponds to a critical stage already known in the rearing of pigs, i.e. growth rate, body composition and food intake. Changes in isocitrate dehydrogenase (ICDH) specific activity were much slighter and differed according to the muscle. There were close correlations between percentages of alphaW fibers and enzymatic kinetic measurements from one month onwards. PMID- 22054930 TI - Effect of different types and locations of the electrode source of an extra low voltage electrical stimulation system on beef quality. AB - An extra low voltage (45V) electrical stimulation (ES) system was used to determine the effects of using different types and locations of the positive electrode and negative ground of the ES system on beef carcass quality. Thirty three Angus heifers (22 months of age) were assigned at slaughter to one of six ES treatments (trt): (1) rectal probe with a ground inserted in the incision made below the brisket during exsanguination, (2) rectal probe with ground inserted in the neck above the atlas joint, (3) rectal probe with a ground attached to the lower mandible, (4) muzzle clamp with a ground inserted in the shackled leg, (5) nasal clamp with a ground inserted in the shackled leg and (6) non-stimulated controls. Stimulation was generated using a full wave rectified pulsating direct current of 16 Hz for a duration of 90s within 3 min of exsanguination. Carcasses were chilled at 2 degrees C and evaluated at 24h post mortem. Regardless of type or where the electrodes were placed within the carcass, all ES trt produced a more rapid drop in pH than the control group. Differences in the effectiveness of the various ES trt on improving meat tenderness were observed. For four selected muscles of the carcass (longissimus, semimembranosus, biceps femoris and triceps brachii) the most consistent and uniform improvement in tenderness was found using ES trt 1 or trt 3. The only drawback associated with trt 1 was the ineffectiveness in eliminating the formation of heat-ring. The other ES trt were successful in alleviating this problem. This study indicates that type and locations of electrode source in an extra voltage ES system are important factors to consider in developing an efficacious low voltage ES system. This work also suggests successful implementation of extra low voltage carcass ES for commercial use if specific types of rectal probe electrode systems are used. PMID- 22054931 TI - Effect of singeing on the texture and histological appearance of pig skin. AB - Singeing of pigs is a necessary process in the manufacture of Wiltshire bacon, but it is a very energy-demanding process. As a preliminary to the development of less expensive methods, the effect of singeing was examined. Skin samples were taken from thirty pig carcasses before and after the singeing process. The changes in the skin were followed by texture measurements, analyses of soluble collagen content and histological measurements of the depth of the effect on the skin microscopically observable. For more detailed histological studies, five carcasses were followed through the slaughtering processes and samples were taken immediately after death, after scalding and de-hairing, after singeing and after removal of the charred skin. The results show that the desired changes in the skin are due to the heat denaturation of the collagen. The same effect is seen after 10 minutes' exposure to water at 60 degrees C. It is therefore possible to change the skin structure at a lower, and less energy-expensive, temperature, but then the hair left from the de-hairing process has to be removed in another way. PMID- 22054932 TI - Fatty acid composition of water buffalo meat. AB - The fatty acid composition of intramuscular lipids of Longissimus dorsi (LD), Psoas major (PM), Biceps femoris (BF), Semitendinosus (ST) muscles and liver of water buffalo male calves was determined by capillary gas-liquid chromatography. The content of total lipids in the LD muscle was found to be maximum, followed by PM, BF and ST in decreasing order (1.03, 0.99, 0.66 and 0.55g/100g of fresh muscle). Liver contained 2.65 g of total lipids per 100 g of fresh tissue. Following the anatomical location, intramuscular lipids contained 44-55% of saturated fatty acids, of which the major components were stearic and palmitic acids. Mono-unsaturated fatty acids (31-40%) composed mainly oleic acid (90%). The PUFA contents in PM, LD, ST and BF were, respectively, 11%, 12%, 13% and 16%. The predominant PUFA were linoleic (66%) and arachidonic (25%). The significance of difference of PUFA content between muscles is discussed. Liver contained 48%, 27% and 22% saturated, monosaturated and PUFA, respectively. The PUFA in liver were linoleic (36%), C20 (47%) and C22 (9%). PMID- 22054933 TI - [Tinea capitis: trends in Spain]. AB - Considerable information is available on the changing incidence, etiology, clinical forms and management of tinea capitis in Spain. While the condition became epidemic during the 19th century, when it was predominantly caused by anthropophilic dermatophytes, the incidence fell with the advent of treatment with griseofulvin, after which zoophilic dermatophytes became the main etiologic agents. Although the true incidence of tinea capitis in Spain today is unknown, the condition continues to be a public health problem. Ongoing changes are evident in the greater diversity of pathogenic species identified and a renewed increase in anthropophilic dermatophytes, especially associated with immigration. Consequently, unless action is taken to correctly diagnose, treat, and prevent this infection, its prevalence may once again reach epidemic proportions in the near future. PMID- 22054934 TI - Present and future prospects of seaweeds in developing functional foods. AB - There has been a combined effort among scientists to explore and utilize varying food sources to develop functional foods to cater the ever-increasing demand from the consumers, who seek health-promoting roles of dietary compounds. Considering the diversity of biochemicals in seaweeds that are capable of exerting bioactivities, a growing trend is developing across globe to employ seaweeds in functional food development. Proteins, peptides, amino acids, polysaccharides, phenolics, lipids, vitamins, and minerals in seaweeds and their functional properties provide insights into the success of potential functional food products that can be developed utilizing seaweeds. However, several factors need to be taken into consideration in designing seaweed-based functional foods to obtain the market success. This chapter elaborates on the prospects of seaweeds in developing seaweed-based functional food products. PMID- 22054935 TI - Nutritional and digestive health benefits of seaweed. AB - Seaweed is a famous delicacy in some parts of the Asia and also a well-known source of important food hydrocolloids, such as agar, alginates, and carrageenan. In addition to the food value of seaweed, several health benefits have also been reported to be present in this valuable food source. It is presumed that the unique features of the marine environment, where the seaweeds are grown, are mainly responsible for most of its properties. Among the functional effects of the seaweed, nutritional and health-related benefits have been widely studied. Compared to the terrestrial plants and animal-based foods, seaweed is rich in some health-promoting molecules and materials such as, dietary fiber, omega-3 fatty acids, essential amino acids, and vitamins A, B, C, and E. In this chapter, the nutritive value of seaweed and the functional effects of its soluble fiber are discussed with a special reference to the digestive health promotion of human. PMID- 22054936 TI - Marine edible algae as disease preventers. AB - As modern lifestyles and new feeding habits settle in the world, noncommunicable diseases (NCDs) have evolved to be major causes of disability in developing as well as developed countries. As a concomitant effect, there is a growing interest in natural, healthy food and an increasing awareness of risk factors and determinants of disease. This chapter describes some nutritional facts about seaweeds, which have been used as food since ancient times in China, Japan, Egypt, and India and comments on the potential utilization of marine algae as functional foods. This concept and the description of metabolic syndrome are used as a basis to comprehension of seaweeds against two dreadful illnesses of our times: high blood pressure and cancer. PMID- 22054937 TI - Potential role of marine algae on female health, beauty, and longevity. AB - Marine environment has been known as a rich source of chemical structures with numerous health benefit effects. Among marine organisms, marine algae have been identified as an underexploited plant resource although they have long been recognized as valuable sources of structurally diverse bioactive compounds. Presently, several lines of studies have provided insight into biological activities of marine algae in promoting female health, beauty, and longevity. Hence, marine algae have a great potential to be used as a part of pharmaceuticals, nutraceuticals, and functional foods. This contribution presents an overview of marine algal potential effect in promoting female health, beauty, and longevity. PMID- 22054938 TI - Sea lettuces: culinary uses and nutritional value. AB - In many countries, sea lettuces are commonly consumed as food by human since the beginning of times. Sea lettuces contain significant amount of nutrients which are essential for human body. Moreover, several studies have provided insight into biological activities and health promoting effects of sea lettuces. Despite having so much health beneficial effects, sea lettuces are still identified as an underexploited plant resources for food purposes. Hence, sea lettuces have a great potential for further development as products in foods and pharmaceutical areas. Further, potential applications of polysaccharides, protein and amino acid, lipid and fatty acid, mineral and vitamin contents may increase the sea lettuces value. This contributions presents information on the currently culinary use of sea lettuces worldwide and nutritional aspects of sea lettuces. PMID- 22054939 TI - Marine algal sources for treating bacterial diseases. AB - Microorganisms are the causative agents for various types of diseases in humans, animals, and plants. The invention of antibiotics against the bacterial diseases in the early twentieth century improved the heath conditions of the humans, but it resulted in the development of variable drug/multidrug-resistant strains which are now posing great challenge to cure the diseases. The need for searching novel bioactive compounds having potential therapeutic value resulted in exploration of oceans. Screening diverse fauna and flora in oceans opened new avenues for the development of novel therapeutic agents such as sesquiterpenes, phlorotannins, bromoditerpenes, halogenated furanones, and algal lectin which show effect on a wide range of Gram-negative and positive bacteria. Hence these bioactive compounds can be used as broad spectrum antibiotics, antibacterial, and antifouling agents. PMID- 22054940 TI - Physical, chemical, and biological properties of wonder kelp--Laminaria. AB - Laminaria is a kelp that finds its place in the brown algae family. It has been an area of study for past many years, and its wonderful biological properties have always attracted medical professionals and researchers to explore more and more from this wonder kelp. The constituents of Laminaria include iodine, potassium, magnesium, calcium and iron. Iodine compounds, TEA-hydroiodide in particular, are great lipolytic agents as they stimulate lipase activity. Laminarins on the other hand are used as a tumor angiogenic blocker. This genus of the kelps is also rich in algin, a high molecular weight polysaccharide that forms viscous colloidal solutions or gels in water leading to the use of kelp derivatives as bulk laxatives. It has great applications in cosmeceutical science, as well as some antibacterial properties have also been assigned to Laminaria. A deeper insight into the physical, biological, and chemical properties of this wonder kelp would lead to further exploitation of Laminaria for medicinal and cosmeceutical purpose. PMID- 22054941 TI - Medicinal effects of phlorotannins from marine brown algae. AB - Brown seaweeds are popular and abundant food in East Asia and also well known for their medicinal effects due to presence of active phenolic constituents. Phlorotannins, the major phenolic group of brown algae, have extensively investigated for their vast array of bioactivities such as antioxidant, anti inflammatory, anticancer, and antidiabetic. They possess promising activity in both in vitro and in vivo systems showing promising potential to further develop as therapeutic agents. In this chapter, attempts have taken to examine and categorize the reports available on active phlorotannins which have shown strong bioactivities. PMID- 22054942 TI - Biological activities and potential health benefits of fucoxanthin derived from marine brown algae. AB - The importance of marine algae as sources of functional ingredients has been well recognized due to their valuable health beneficial effects. Therefore, isolation and investigation of novel bioactive ingredients with biological activities from marine algae have attracted great attention. Among functional ingredients identified from marine algae, fucoxanthin has received particular interest. Fucoxanthin has been attributed with extraordinary potential for protecting the organism against a wide range of diseases and has considerable potential and promising applications in human health. Fucoxanthin has been reported to exhibit various beneficial biological activities such as antioxidant, anticancer, anti inflammatory, antiobesity, and neuroprotective activities. In this chapter, the currently available scientific literatures regarding the most significant activities of fucoxanthin are summarized. PMID- 22054943 TI - Phlorotannins and fucoidans from marine macroalgae as matrix metalloproteinase inhibitory substances and their possible application as medicinal foods. AB - Metalloproteinases especially matrix metalloproteinases are a group of endopeptidases that contribute for the extracellular matrix degradation, and several tissue remodeling processes. Improper regulation of these endopeptidases could lead to several severe pathological problems that include cardiac, cartilage, and cancer-related diseases. Until now, many synthetic matrix metalloproteinase inhibitory substances (MMPIs) have been reported; however, many of them could not make to the final clinical trials. Hence, the emphasis on screening of MMPIs from different natural resources has gained much importance and marine resources are one among them. As marine organisms have been contributing with several biologically active compounds that have profound applications in nutraceuticals, cosmeceuticals, and pharmaceuticals; in this chapter, an attempt has been made to discuss the various MMPIs from edible seaweeds, which could be considered as medicinal foods. PMID- 22054944 TI - Protective effect of polysaccharide from Hizikia fusiformis against ethanol induced toxicity. AB - Polysaccharide extracted from Hizikia fusiformis (Hf-PS-1) exhibited protective effects against ethanol-induced peptic injury. In in vivo assay, the ethanol group exhibited decrease of total glutathione (GSH) and increase of jun N terminal kinase (JNK) phosphorylation relative to the control group, whereas levels were significantly increased and decreased, respectively, in the Hf-PS-1 group. Hf-PS-1 reduced ethanol-induced gastric injury. In in vitro assay, ethanol induced IEC-6 cells' death in a dose-dependent manner. Ethanol decreased the phosphorylation of Shc and the binding of Grb2 to Shc, and Hf-PS-1 pretreatment increased them. Ethanol also induced the phosphorylation of JNK and extracellular signal-regulated kinase (ERK), whereas Hf-PS-1 pretreatment decreased JNK activation but not ERK. Co-treatment with JNK inhibitor and ethanol decreased GSH levels, indicating that JNK phosphorylation is a critical factor during ethanol induced injury. Therefore, Hf-PS-1 may be useful to protect against ethanol induced gastrointestinal injury. PMID- 22054945 TI - Functional properties of brown algal sulfated polysaccharides, fucoidans. AB - Marine algae are potentially prolific sources of highly bioactive components that might represent useful leads in the development of new pharmaceutical agents and functional foods. This chapter discusses the current literature on biological activities of sulfated polysaccharides, fucoidans, from brown seaweeds. The profound functional properties of fucoidans could be employed in pharmaceutical, nutraceutical functional food, and cosmeceutical applications. Therefore, the chapter deals with the functional properties of the sulfated polysaccharides, fucoidans, with reference to its industrial applications as a functional ingredient. PMID- 22054946 TI - Polysaccharides from Capsosiphon fulvescens stimulate the growth of gastrointestinal cells. AB - Capsosiphon fulvescens is a green alga that is abundant along the southwest coast of South Korea. Although it is consumed for its purported health-enhancing properties, particularly as a treatment for stomach disorders and hangovers, the health effects of dietary C. fulvescens remain unclear. Polysaccharides extracted from C. fulvescens (Cf-PS) are investigated for their effects on the proliferation of rat small intestinal epithelial IEC-6 cells. Cf-PS stimulated IEC-6 cell proliferation in a dose-dependent manner. Further, Cf-PS treatment induced the translocation of beta-catenin, an effector of the Wnt signaling pathway, from the cytosol to the nucleus and increased the expression of cyclinD1 and c-myc. Cf-PS also induced ERK1/2 phosphorylation, which is activated by mitogenic and proliferative stimuli such as growth factors, but the phosphorylation of JNK and p38 was not enhanced. Therefore, this chapter discusses the effect of Cf-PS on the growth of gastrointestinal cells. PMID- 22054947 TI - Potential beneficial effects of marine algal sterols on human health. AB - The importance of bioactive derivatives as functional ingredients has been well recognized due to their valuable health beneficial effects. Therefore, isolation and characterization of novel functional ingredients with biological activities from marine algae have gained much attention. Sterols are important structural component of cell membranes. It has been reported that plant sterols exhibit various beneficial biological activities such as hypercholesterolemic, antioxidant, anticancer, antidiabetic, antihypertensive, anti-inflammatory, antifungal, and antibacterial activities. Marine algae with a great diversity can be a very interesting natural resource of sterols. This chapter focuses on biological activities of marine algae derived sterols with potential health beneficial applications in functional foods and pharmaceuticals. PMID- 22054948 TI - Laminaria japonica as a food for the prevention of obesity and diabetes. AB - Various seaweeds have traditionally been used as flavoring materials, food additives, and foodstuffs in many countries, especially those in Asia. The seaweed Laminaria japonica (LJ) is popular as "kombu" in Japanese cuisine. Laminaria sp. is one of the most important marine medicinal foodstuffs, as its biological functions have been widely investigated in both in vitro and in vivo experiments. This chapter introduces recent reports on the ability of Laminaria to prevent obesity and diabetes, and some approaches for effectively using the bioactivities found in Laminaria. The inhibitory effects of Laminaria sp. on triglyceride absorption were investigated in triglyceride-loaded mice and in mice with high-fat-diet-induced obesity. Shaved Laminaria, known as "tororokombu," showed more effective activities in these experiments. The active component was considered to be alginic acid in the water-soluble fraction. On the other hand, the antihyperglycemic effects of a hot water extract of immature Laminaria were investigated in carbohydrate-loaded mice and in in vitro experiments using Caco-2 cells. The potential usefulness of Laminaria sp. as marine medicinal foods may be increased through the use of different processing methods and/or growth stages. These reports suggest that LJ may be useful for preventing lifestyle-related diseases. PMID- 22054949 TI - Anticancer compounds from marine macroalgae and their application as medicinal foods. AB - Cancer is one of the most challenging medical conditions that need a proper therapeutic approach for its proper management with fewer side effects. Until now, many of the phytochemicals from terrestrial origin have been assessed for their anticancer ability and few of them are in clinical trials too. However, marine environment also has been a greatest resource that harbors taxonomically diverse and a variety of life forms and serves as store house for several biologically beneficial metabolites. Hitherto, many metabolites have been isolated from marine biomasses that have exhibited excellent biological activities, especially as anticancer agents. In particular, marine macroalgae which are considered as dietary constituents in Pacific Asian region have become chief resources for their unparalleled and unique metabolites like sulfated polysaccharides (SPs), phlorotannins, and their ability in reducing the risk of cancer and its related diseases. In this chapter, we have discussed the anticancer activities of marine algae-derived SPs, phlorotannins, and carotenoids and the possibilities of marine algae as potential medicinal foods in the management of cancer. PMID- 22054950 TI - Marine algae: natural product source for gastrointestinal cancer treatment. AB - Among marine organisms, marine algae are rich sources of structurally diverse bioactive compounds with various biological activities. In order to survive in a highly competitive environment, freshwater or marine algae have to develop defense strategies that result in a tremendous diversity of compounds from different metabolic pathways. Recently, their importance as a source of novel bioactive substances is growing rapidly and many reports have been published about isolated compounds from algae with biological activities. Many researchers reported anticancer activity of the compounds isolated from marine algae. Gastrointestinal tract cancer is one of the most frequent death causes of cancer in men and women. Especially stomach cancer and colon cancer are the second and third common cancer type in the world after lung cancer. Hence investigation of bioactive compounds against gastrointestinal cancer cells has recently become an important field for researchers. PMID- 22054951 TI - Anticoagulant effect of marine algae. AB - Recently, a great deal of interest has been developed in the nutraceutical and pharmaceutical industries to isolate natural anticoagulant compounds from marine resources. Among marine resources, marine algae are valuable sources of novel bioactive compounds with anticoagulant effect. Phlorotannins and sulfated polysaccharides such as fucoidans in brown algae, carrageenans in red algae, and ulvans in green algae have been recognized as potential anticoagulant agents. Therefore, marine algae-derived phlorotannins and SPs have great potential for developing as anticoagulant drugs in nutraceutical and pharmaceutical areas. This chapter focuses on the potential anticoagulant agents in marine algae and presents an overview of their anticoagulant effect. PMID- 22054952 TI - Potential application of marine algae as antiviral agents in medicinal foods. AB - Viral diseases, caused by pathogenic virus infections, are still the leading cause of death in humans worldwide. Although many antiviral agents have been developed and are used for treatment of infectious diseases, emergence of drug resistance, side effects, and the necessity for extensive clinical use are the main reasons for failure of antiviral therapy. Therefore, the development of new antiviral agents with diverse kinds of antiviral actions is required. The search for new antiviral agents focuses on not only synthetic compounds but also natural products such as plants, insects, animal organs, and their components. Recently, a great deal of interest has been expressed regarding marine algae as potential antiviral agents. This contribution focuses on antiherpes virus therapeutic agents derived from marine algae which are considered as novel functional ingredients in antiherpes virus therapy. PMID- 22054953 TI - Anti-HIV activity of extracts and compounds from marine algae. AB - In recent years, elucidation of novel bioactive substances from different marine organisms is gaining importance rapidly not only from the research and publications but also from controlled clinical studies of natural product-derived substances. They offer important leads for the development of antiviral drugs against viral infections caused by human immunodeficiency virus type 1 (HIV-1). Regarding this issue, numerous anti-HIV-1 therapeutic agents from marine resources have been reported for their potential medicine/medical application as novel functional ingredients in anti-HIV therapy. In detail, marine macroalgae have attracted much of attention as a reliable source for potential anti-HIV compounds. Up to date, several types of compounds such as tannins, polysaccharides, lectins, and derivatives have been isolated, identified, and reported to possess significant anti-HIV-1 activity. PMID- 22054954 TI - Antiallergic benefit of marine algae in medicinal foods. AB - The prevalence of allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis has increased during the past two decades and contributed a great deal to morbidity and an appreciable mortality in the world. Until now, few novel efficacious drugs have been discovered to treat, control, or even cure these disorders with a low adverse-effect profile. Meanwhile, glucocorticoids are still the mainstay for the treatment of allergic disease. Therefore, it is essential to isolate novel antiallergic therapeutics from natural resources. Recently, marine algae have received much attention as they are a valuable source of chemically diverse bioactive compounds with numerous health benefit effects. This contribution focuses on antiallergic agents derived from marine algae and presents an overview of their potential application in medicinal foods for the treatment of allergic disorders. PMID- 22054955 TI - Marine macro- and microalgae as potential agents for the prevention of asthma: hyperresponsiveness and inflammatory subjects. AB - Asthma is a variable disease and various factors are affected to increase the asthmatic symptoms and level of asthma control. It is believed that the cause for this disease is a combination of genetic and environmental factors. Numerous medications are available at present to treat this disease but it has been failed to control number of incidences successfully. Hence, recently many researchers have paid their interest to identify potential drugs from marine-based resources such as marine algae. In vitro and in vivo experiments have been conducted with extracts or compounds from algae and found that they showed significant activities against asthma. Accordingly, many marine macro- and microalgae have been reported to have potential to ameliorate the effect of asthma. However, detailed studies are needed in relation to identify the molecular mechanism of this disease to apply those marine resources against asthma effectively. In this chapter, an attempt has been taken to discuss the potential antiasthmatic activity of marine macro- and microalgae. PMID- 22054956 TI - Impact of marine micro- and macroalgal consumption on photoprotection. AB - The enormousness of species diversity of oceans leads to the isolation and development of health- and beauty-enhancing components from various marine organisms. The significance of these marine-derived compounds or substances has been scientifically well implied for various biological and biomedical parameters. One such important parameter is photoprotectivity, which is the major concern nowadays because of the depletion in ozone layer and the possible high risk of UV irradiation to humans. The marine macro- as well as microalgae and their food products, knowingly and unknowingly, have been used since hundreds of years. These foods possess tremendous implications in defending the highly hazardous UV radiation, thereby facilitating photoprotection to humans. In addition, based on the recent studies, many of the UV-protecting algal species is directed for the use as medicinally valuable foods and food ingredients. This chapter describes certain micro- and macroalgal species along with their photoprotective importance. PMID- 22054957 TI - Seaweed proteins and amino acids as nutraceuticals. AB - Seaweeds demonstrate original and interesting nutritional characteristics. Protein concentration ranges from 5% to 47% of dry basic. Its value depends particularly on species and the environmental conditions. Seaweed protein is a source of all amino acids, especially glycine, alanine, arginine, proline, glutamic, and aspartic acids. In algae, essential amino acids (EAAs) represent almost a half of total amino acids and their protein profile is close to the profile of egg protein. In case of non-EAAs, all three groups (green, brown, and red seaweeds) contain the similar amount. Red seaweed seems to be a good source of protein because its value reaches 47%. The issue of protein malnutrition supports the trend to find a new and cheap alternative source of protein. Algae could play an important role in the above-mentioned challenge because of relatively high content of nitrogen compounds. Algae may be used in the industry as a source of ingredients with high nutritional quality. PMID- 22054958 TI - Medicinal effects of peptides from marine microalgae. AB - Nowadays, there are numerous commercial applications of microalgae, and they have been used to enhance the nutritional value of food and animal feed owing to their chemical composition. They are cultivated as a source of highly nutritional and valuable source. Recently, microalgae have been reported to use as a potent source for food additive, nutraceutical, or pharmaceuticals. According to the criteria of nutritional quality and cost, variety of marine organisms has been investigated for their suitability to be applied in the production of protein hydrolysates in functional foods. Recently, a great deal of interest has been expressed regarding marine-derived bioactive peptides because of their numerous health benefits. In addition, many studies have been reported that marine bioactive peptides can be used as functional foods, nutraceuticals, or pharmaceuticals due to their therapeutic potential in the treatment or prevention of various diseases. Hence, in this chapter, we discussed the importance of marine microalgae in relation to their medicinal value. PMID- 22054959 TI - Seaweed as a source of novel nutraceuticals: sulfated polysaccharides and peptides. AB - Seaweeds and seaweed-derived products are underexploited marine bioresources and a source of natural ingredients for functional foods. Nutritional studies on seaweeds indicate that brown and red seaweeds possess a good nutritional quality and could be used as an alternative source of dietary fiber, protein, and minerals. Moreover, bioactive sulfated polysaccharides are the main components of soluble fiber in seaweeds and also bioactive peptides can be prepared from seaweed protein. This chapter gives an overview of the main biological properties of sulfated polysaccharides and peptides from brown and red seaweeds. Recent studies have provided evidence that sulfated polysaccharides from seaweeds can play a vital role in human health and nutrition. Besides, peptides derived from algal protein are most promising as antihypertensive agents. Further research work, especially in vivo studies, are needed in order to gain a better knowledge of the relation structure-function by which bioactive compounds from seaweeds exert their bioactivity. PMID- 22054960 TI - Seaweed lipids as nutraceuticals. AB - Seaweeds are known as low-energy food. Despite low lipid content, omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) introduce a significant part of seaweed lipids. PUFAs are the important components of all cell membranes and precursors of eicosanoids that are essential bioregulators of many cellular processes. PUFAs effectively reduce the risk of cardiovascular diseases, cancer, ostheoporosis, and diabetes. Because of the frequent usage of seaweeds in Asia and their increasing utilization as food also in other parts of the world, seaweeds could contribute to the improvement of a low level of omega-3 PUFAs, especially in the Western diet. The major commercial sources of omega-3 PUFAs are fish, but their wide usage as food additives is limited for the typical fishy smell, unpleasant taste, and oxidative nonstability. Nevertheless, growing requirements of healthy functional foods have led to produce PUFAs as nutraceuticals in controlled batch culture of marine microalgae, especially Thraustochytrium and Schizochytrium strains. PMID- 22054961 TI - Seaweed vitamins as nutraceuticals. AB - Seaweeds are a good source of some water- (B(1), B(2), B(12), C) and fat-soluble (beta-carotene with vitamin A activity, vitamin E) vitamins. To ensure that the adequate intake of all vitamins is received in the diet, people (especially people on special diet, strict vegetarians, and vegans) can consume foods enriched with vitamins, for example, in the form of functional foods with vitamins as nutraceuticals, extracted from natural sources such as seaweeds. Seaweed vitamins are important not only due to their biochemical functions and antioxidant activity but also due to other health benefits such as decreasing of blood pressure (vitamin C), prevention of cardiovascular diseases (beta carotene), or reducing the risk of cancer (vitamins E and C, carotenoids). PMID- 22054962 TI - Seaweed minerals as nutraceuticals. AB - Seaweed is known as an abundant source of minerals. Mineral composition of seaweed is very changeable because of many exogenous and endogenous factors and differs also within the same species. Principally, seaweed is an excellent source of some essential elements. Mainly, iron and iodine are in high concentration. Seaweeds could be prospective as functional foods and also producers of mineral nutraceuticals. PMID- 22054963 TI - Medicinal benefits of sulfated polysaccharides from sea vegetables. AB - The cell walls of sea vegetables or marine algae are rich in sulfated polysaccharides (SPs) such as fucoidans in brown algae, carrageenans in red algae, and ulvans in green algae. These SPs exhibit various biological activities such as anticoagulant, antiviral, antioxidative, and anticancer activities with potential health benefits. Therefore, SPs derived from sea vegetables have great potential in further development as nutraceuticals and medicinal foods. This chapter presents an overview of biological activities and potential medicinal benefits of SPs derived from sea vegetables. PMID- 22054964 TI - The perspectives of the application of biofilm in the prevention of chronic infections. AB - Biofilms are a natural part of the ecology of the earth. Many biofilms are quite harmful and must be treated or controlled. Other biofilms are beneficial and can be used to help fix serious problems. Biofilms can grow on many different surfaces, including rocks in water, foods, teeth, and various biomedical implants. This bacterial colonization may present the need for additional operations, amputation, or it may even lead to death. The fundamental principles of bacterial cell attachment and biofilm formation are discussed. Biofilms represents a new, wide-open field practice and research that is only going to get hotter with time. Functional organic plasma polymerized coatings are also discussed for their potential as bio-sensitive interfaces, connecting metallic electronic devices with their physiological environments. PMID- 22054965 TI - Osteoporosis treatment: marine algal compounds. AB - Osteoporosis is one of the most common bone diseases that occur due to imbalance during bone formation and bone resorption. About half of all women over the age of 50 will have a fracture on the hip, wrist, or vertebra. Research and treatment of osteoporosis are challenging for researchers and physicians. There are several types of treatments for osteoporosis including most famous bisphosphonates, estrogen agonists/antagonists, parathyroid hormone, estrogen therapy, hormone therapy, and recently developed RANKL inhibition. In the recent days, much attention has been paid for marine algal extracts and compounds for osteoporosis treatment. In this chapter, we extensively deal with marine algae compounds and their rich mineral constituents for osteoporosis treatment. PMID- 22054966 TI - Marine algae possess therapeutic potential for Ca-mineralization via osteoblastic differentiation. AB - One of the important natural product investigations from marine algae is to focus on the pharmaceutically important compounds that can be applied in bone health. Osteoporosis is one of the bone diseases caused by an imbalance between bone formation and resorption. Promotion of osteoblast differentiation is one of the best therapeutic ways to combat osteoporosis. Osteoblasts are the cells responsible for bone formation by increasing the proliferation of the osteoblastic lineage or inducing differentiation of the osteoblasts. In this review, we describe the central effects of osteoblast differentiation by various bone therapy biomaterials from marine algae. PMID- 22054967 TI - Extracts of marine algae show inhibitory activity against osteoclast differentiation. AB - Osteoclasts are multinucleated cells that play a crucial role in bone resorption. The imbalance between bone resorption and bone formation results in osteoporosis. Therefore, substances that can suppress osteoclast formation are potential candidate materials for drug development or functional foods. There have been reports that extracts or purified compounds from marine micro- and macroalgae can suppress osteoclast differentiation. Symbioimine, isolated from the cultured dinoflagellate Symbiodinium sp., had suppressive effects against osteoclast differentiation in osteoclast-like cells. Norzoanthamine, isolated from the colonial zoanthid Zoanthas sp., has been shown to have antiosteoporosis activity in ovariectomized mice. With regard to marine extracts, the fucoxanthin-rich component from brown algae has been shown to have suppressive effects against osteoclast differentiation. An extract of Sargassum fusiforme has recently been shown to have antiosteoporosis activity. This extract suppressed both osteoclast differentiation and accelerated osteoblast formation in separate in vitro experiments. It also showed antiosteoporosis activity in ovariectomized mice by regulating the balance between bone resorption and bone formation. These marine algae and their extracts may be sources of marine medicinal foods for the prevention of osteoporosis. PMID- 22054968 TI - Sea vegetables. Preface. PMID- 22054969 TI - Methods of predicting pale, soft, exudative pork and their application in breeding programmes-A review. AB - The condition of pale, soft, exudative (PSE) pork has long been considered to be mainly a post mortem phenomenon. There is now substantial evidence that such pigs are suffering from a kind of myopathy, which predisposes them to an abnormal post mortem metabolism. Genetic studies on PSE muscle indicate a moderate heritability for various post mortem muscle quality traits. Reliable methods for determining the abnormal condition in the live animal would make it possible to select more effectively and economically against stress and PSE-susceptibility. Three possible methods are: (1) Analysis of blood serum for CPK, aldolase, GOT or other enzyme activities with and without preceding exercise; and for blood groups. (2) Muscle biopsy analysis for glucose-6-phosphate, lactate or energy-rich phosphates. (3) Non-destructive testing of young pigs for sensitivity to the Malignant Hyperthermia Syndrome by allowing them to inhale the anaesthetic halothane (fluothane) for a 5 min period. The development of muscular rigidity and stiffness indicates a susceptibility to stress and a potential for PSE meat. The relationships of the various methods to ultimate muscle and carcass quality, as well as the problems inherent to each method, are discussed. It is concluded that the third test seems to be the most promising for application in the breeding of pigs for optimal stress resistance and muscle quality. PMID- 22054970 TI - Variability in rates of pH fall and of lactate production in the muscles on cooling beef carcasses. AB - The rate of pH fall in four major muscles on cooling beef carcasses varied by about twofold. Thus the time taken to reach pH 6.0 from initial pH values of about 7.1 varied between 8 and 16h, and in one extreme case of an LD muscle was as low as 3.5 h. Some of this variability was due to different rates of cooling between muscles in the same animal, but even after correction of the rates to a constant temperature of 38 degrees C the variability was still about twofold in the higher range of pH (7.0-6.7) and slightly lower in the lower range (6.6-5.8). Similar variability was shown in excised TB muscles, kept at a constant temperature of 38 degrees C. Damage to muscles during excision can lead to much higher variability than this (in rabbit LD muscles, to about sixfold). The rate of pH fall is determined by the rate of ATP-turnover, and so the variability in the former rate is likely to be due to varying intracellular free Ca(2+) levels exerting a stimulating effect on the actomyosin ATP-ase. Some of this extra Ca(2+) may arise from calcium release from mitochondria as they become anaerobic after death. PMID- 22054971 TI - Mixed protein fibres from meat industry by-products. AB - Mixtures of bovine blood plasma, lung and rumen protein isolates were texturised into a fibrous form containing up to 21% protein. Fibres containing rumen protein in admixture had a greater resistance to shear. The colour of the fibres was dependent upon the proportion of lung in the mixture; reflectance spectra of mixed protein fibres resembled those of cooked meat. Electrophoretograms of the fibres were characterised by the presence of a dense band in close proximity to the origin. Mixing protein species did not produce any electrophoretic component other than those originally present. It would be expected that mixtures of these proteins would produce protein fibres of satisfactory nutritive value. PMID- 22054972 TI - Destruction of Escherichia coli and salmonellae on mutton carcases by treatment with hot water. AB - Laboratory experiments showed that the surface tissues of beef and mutton samples were not permanently discoloured to an objectionable extent by treatment with water at 80 degrees C or 10 sec. This treatment destroyed more than 99% of the numbers of E. coli and salmonellae inoculated on the beef samples and more than 99.9% of the same organisms inoculated on the exterior surfaces of tissue taken from sheep carcases. Immersion in water at 80 degrees C for 10 sec of whole sheep carcases taken off the end of the slaughter line in a commercial abattoir destroyed c. 99% of the contaminating coliform organisms and c. 96% of the total number of aerobic bacteria initially present on the surface tissues. The application of such a treatment to sheep carcases in abattoirs should substantially reduce any salmonella contamination on the meat and may improve storage life. Although initially discoloured to a depth of 0.5 mm by the treatment, sheep carcases heated at 80 degrees C for 10 sec almost completely regained their normal appearance within a few hours during subsequent chilled storage at 1-4 degrees C. PMID- 22054973 TI - Ultrastructural changes in bovine Longissimus muscle during postmortem ageing. AB - The ultrastructural changes in type 1 (red) and type 2 (white) myofibres of the longissimus muscle were studied during in situ postmortem ageing in a group of young Hereford bulls, 14-16 months old. Type 1 myofibres were defined as those having wide, dense and distinct Z-discs and type 2 myofibres were those with narrower and less distinct Z-discs. Type 1 myofibres also had numerous intermyofibrillar mitochondria and type 2 myofibres had few intermyofibrillar mitochondria. Three time periods were studied-1 h, 48 h and 216 h postmortem. Type 1 myofibre Z-discs were essentially unaltered at all three postmortem time periods studied. Type 2 myofibres showed limited degradation (loss) of Z-disc material at 1 h postmortem, but degradation had increased at 48 h. However, little additional Z-disc degradation occurred between 48 h and 216h. Both type 1 and type 2 myofibres underwent myofibrillar fragmentation at the level of the Z disc and I-band which was independent of Z-disc degradation. The most tender longissimus muscles tended to have more fragmentation at the Z-disc-I-band junction than the toughest muscle samples. PMID- 22054974 TI - Changes of physical and chemical properties and of histological structure of meat subjected to massage under vacuum. AB - Differences were found in a number of attributes (pH value, changes in volume and linear dimensions, cooking loss, tenderness and water-holding capacity) between porcine muscles subjected to vacuum massage and those in non-massaged controls. Histologically there were changes in the structure of massaged muscles. The content of connective tissue in massaged meat appears to influence water-holding capacity and cooking loss to some extent. PMID- 22054975 TI - Factors affecting the residual blood content of meat. AB - From estimates of the residual blood content of muscles from rats killed while stressed or under barbiturate anaesthesia it appears that, at slaughter, the stress associated with stunning and exsanguination will normally produce peripheral vasoconstriction through the action of released catecholamines. This will result in minimal retention of blood in the skeletal muscles while factors which reduce vascular tone will lead to higher levels of residual blood in meat. PMID- 22054976 TI - The use of muscle protein solubility measurements to assess pig lean meat quality. AB - The relationships between sarcoplasmic, myofibrillar and total soluble protein (sarcoplasmic + myofibrillar) concentrations, and subjective (colour-structure score) and objective (drip loss and reflectance) measures of lean meat quality were determined using 100 samples of M. Longissimus dorsi that showed a wide range of quality. There was good agreement between the subjective and objective assessments of quality. Overall, the concentration of soluble sarcoplasmic proteins showed the highest correlations with quality assessments. The relationships with total soluble protein were poorer and were least good with myofibrillar protein concentration. Sarcoplasmic protein concentration was also the best potential predictor of meat quality when pale, soft, exudative (PSE) muscles were excluded from the sample. However, if dark, firm, dry (DFD) muscles were excluded instead, the concentration of total soluble protein was as good as, or better than, sarcoplasmic protein as a potential predictor of quality, particularly muscle reflectance. PMID- 22054977 TI - Effects of salt reduction on the rheological and gelation properties of beef, pork and poultry meat batters. AB - The gelation and rheological properties of beef, pork and poultry meat batters as affected by salt reduction (2.50, 1.25 and 0.00%) were studied by using a Haake rotational viscometer and a thermal scanning rigidity monitor. Beef batters showed a decrease in shear stress with the decrease in salt levels at both high and low shear rates. Pork batter showed a mixed behavior (no definite trend in shear stress versus shear rate) and the poultry meat batters showed a Bingham pseudoplastic behavior, except for the no-salt treatment. During heating the beef batters showed the highest G values followed by the pork and the poultry meat batters. The rigidity modulus profiles exhibited two major transition temperatures at 47-53 degrees C and at 64-76 degrees C. Beef batter with 2.50% salt developed the highest average G value (16.6 kPa) and the poultry batter with 2.50% salt the lowest (7.3 kPa). PMID- 22054978 TI - Comparison of analytical methods. AB - A technique for comparing two analytical methods is presented in this paper. Frequently a new method, generally simpler, faster or less expensive, is compared with a reference method. The deterministic relationships between two methods, subject only to random errors, is first discussed. However, the relationship between two methods may be stochastic (non-deterministic); this problem is also discussed here. The concept of the sensitivity ratio of Mandel furnishes an appropriate basis of comparison. The use of the correlation coefficient may be completely erroneous for this purpose. Tests are presented for the significance of constants in the regression equation. Dangers in the use of stochastic relationships are strongly emphasized because of the unstable estimation of constants in the regression formula. Some systematizing principles not generally known by food scientists are presented here. PMID- 22054979 TI - The role of the endomysium in the salt-induced swelling of muscle fibres. AB - Variable uptake of water is a persistent problem in meat processing. To try to understand the changes that occur during water uptake, and thereby explain this variability, we have measured the swelling of salt-treated single muscle fibres from rabbit longissimus dorsi. By dissolving out the myofibrillar proteins with SDS we have been able to tell whether or not a dissected fibre has an endomysial connective sheath. We find that some fibres do lack a sheath and that these stripped fibres swell on average approximately five times more than intact fibres in 0.25 m KI. This shows that the endomysium limits the swelling of the fibre in salt, as is also shown by the greater swelling of those parts of fibres from which the endomysium has been deliberately removed. On prolonged immersion in 0.25 m KI the stripped parts of fibres shrink after swelling whereas the smaller swelling of unstripped parts is maintained. With careful, slow dissection, the proportion of stripped fibres is low at all times post mortem, but if a quicker method is used, the proportion of stripped fibres increases with time post mortem. As ageing proceeds, an increasing incidence of transverse fractures reduces the productivity of the quicker method, so the slow method has to be used. Regardless of the method of dissection the swelling of stripped and unstripped fibres does not depend on time post mortem. Thus it is the changing proportion of stripped fibres that underlies the earlier report (Wilding et al. Meat Sci., 1986 18, 55) of a dependence of swelling on time post mortem. The ease of stripping of endomysium from muscle fibres may be important in meat processing. Thus whether or not fibres produced during comminution and mixing of meat are stripped directly affects water uptake. The extraction of myofibrillar proteins may also be affected, which would be important for the adhesion of cooked reformed meat products. PMID- 22054980 TI - Influence of straw feeding and growth-implant on veal meat quality. AB - Trials have been carried out to examine the effects of a food additive supply (Maturex) and/or of anabolic implant (Revalor) on carcass characteristics and on veal meat qualities. Twelve Holstein * Francaise Frisonne Pie Noire calves acted as controls, twelve calves were implanted with Revalor, approximately 60 days prior to slaughter, twelve others were fed with Maturex, whilst the remaining twelve animals were fed with Maturex and implanted with Revalor. All animals were slaughtered at 4 months. Revalor implantation had a significant effect on carcass weight and conformation. Feeding with Maturex had no significant effect on different carcass characteristics. Neither anabolic treatment nor Maturex supplementation significantly affected pH value, haematocrit, pigment content, FOP, colour characteristics, collagen content and solubility, or dry matter. Although Revalor had a negative effect on weight losses during cooking, Maturex showed no significant effect. While Maturex showed a positive effect on tenderness and no effect on juiciness, Revalor showed a negative effect on tenderness and juiciness. For all sensory characteristics, no effect was noted when both Maturex and Revalor were used together. PMID- 22054981 TI - Obituary. PMID- 22054982 TI - Correlation of histopathology with magnetic resonance imaging in Kienbock disease. AB - PURPOSE: Diagnosis and treatment remain controversial for Kienbock disease. A few reports have correlated magnetic resonance imaging (MRI), which is essential for early diagnosis, and histopathology of Kienbock biopsy specimens, but histopathological correlations of whole lunate bones or histological slices compared with MRI images are lacking. The purpose of this study was to compare presurgical MRI scans with corresponding histological slices of Kienbock-diseased lunates. METHODS: We excised whole lunates at the time of surgery from 6 patients with Kienbock disease (stage IIIB) undergoing tendon-ball replacement or a Graner procedure. We stained paraffin-embedded, coronally sectioned specimens with hematoxylin-eosin and compared them with presurgical coronal scans using MRI with a 47-mm microscopy surface coil. RESULTS: Toward the center of the lunates, the signal intensity in the proton density-weighted images was reduced, whereas the dorsal and palmar sides of the lunates exhibited no changes in intensity. In correlation, histopathological findings revealed strongly disrupted trabeculae toward the center of the lunates and intact trabeculae in the dorsal side of the lunates. Likewise, the necrotic and vitalized bone exhibited low and high signal intensities, respectively, in the proton density-weighted images; however, in the fast-field echo images, there were no correlations with histopathological observations. CONCLUSIONS: Proton density-weighted MRIs but not fast-field echo images using a 47-mm microscopy coil reflected the extent and localization of the necrotic area in Kienbock-diseased lunates, as evidenced by comparison with histological analyses of the lunate specimens. CLINICAL RELEVANCE: Proton density weighted MRIs accurately reflect the vascular status of the lunate and may help plan treatment on a case-by-case basis. PMID- 22054983 TI - Update on nonautogenous interposition arthroplasty for thumb basilar joint arthritis. PMID- 22054984 TI - Osseous and ligamentous scaphoid anatomy: Part II. Evaluation of ligament morphology using three-dimensional anatomical imaging. AB - PURPOSE: There are many controversies in the literature regarding the morphology of the scaphoid ligaments. The aim of this study was to provide a more accurate description by quantitatively describing the 3-dimensional, geometrical aspects of the scaphoid ligaments and their attachments, using cryomicrotome images of cadaveric wrists. METHODS: Eight fresh-frozen human cadaver wrists were examined with computed tomography (CT) and an imaging cryomicrotome. A series of 2 dimensional cryoimages created a 3-dimensional anatomical data set of each test specimen. Detection of ligaments and their surface areas was performed by manually marking the course and attachment points for each ligament, using dedicated visualization software. The 3-dimensional bone surfaces were segmented from the acquired CT images and incorporated in the 3-dimensional anatomical data set of the same anatomical specimen to facilitate the detection procedure. The results of the morphological parameters and attachment areas of the scaphoid ligaments are described 3-dimensionally. RESULTS: The mean size of the whole scaphoid surface was 1503 +/- 17 mm(2), and the mean size of all ligament attachments on the scaphoid was 131 +/- 14 mm(2); thus, ligament attachments consist of 9% +/- 0.9% of the total scaphoid surface area. Based on the data, a 3 dimensional representation of the wrist was created to present the scaphoid ligament attachment areas and paths. The dorsal intercarpal ligament had the most individual variability between specimens in attachments. CONCLUSIONS: The quantitative results were almost completely consistent with the findings of previous reports. The only inconsistency in ligament morphology regarded the scaphocapitate ligament, which in this study was found to be the thickest ligament attached to the scaphoid. CLINICAL RELEVANCE: The results of this study improve our knowledge of scaphoid ligament anatomy, as they corroborate previous findings. This is important for carpal surgery and will pave the way to a better understanding of the biomechanics involved in destabilization of wrist fractures. PMID- 22054985 TI - Influence of age at slaughter, rearing technique and pre-slaughter treatment on some quality traits of lamb meat. AB - The influences of rearing technique and age on muscle fibre type, and of rearing technique, age and pre-slaughter transport on the meat quality characteristics of sheep were investigated using thirty lambs of a Bulgarian coarse-fleeced breed (Karakatchanska). The animals were reared on pasture or in barns and slaughtered at 22 or 30 weeks of age. Muscle fibre type and meat quality were studied in three muscles of different metabolic type-Longissimus dorsi (LD), Supraspinatus (SS) and Rectus abdominis (RA). Fibre type distribution was influenced by age but not by rearing technique. Pigment content of muscles was higher in older animals. Water binding capacity (WBC) increased-and cooking loss decreased-with age. There was an interaction between muscle and pre-slaughter stress with respect to pH, the latter being increased in SS muscle, as was WBC. Cooking loss was decreased by transport stress in the three muscles and by pre-slaughter stress. However, meat organoleptic characteristics (flavour, tenderness and juiciness, as judged by a taste panel) were not influenced by age, rearing technique or pre-slaughter treatment. PMID- 22054986 TI - Prediction of lamb meat quality traits based on muscle biopsy fibre typing. AB - The aim of the experiment described in this paper was to determine the relationship between muscle fibre type and meat quality. Two indicator muscles, the Stylohyoideus and the Scutulo auricularis superficialis accessorius, were biopsied on one-month-old lambs and used as an index to select the animals of the redder and of the whiter metabolic types among the lamb population studied. Evaluation of the organoleptic qualities of meats from two groups was performed on the Longissimus dorsi muscle by a taste panel. The results of the taste panel evaluation suggest, on one hand, that the meat from the redder animals is juicier and has a more intense flavour than that from the whiter. On the other hand, it appears possible to obtain an in vivo prediction of lamb meat quality based on muscle biopsy fibre typing. PMID- 22054987 TI - Effect of conditioning and carcass posture on eating quality of mutton from old Bannur ewes. AB - Twenty-six mature ewes of an indigenous mutton breed, slaughtered and dressed conventionally, were used for the experiment described in this paper. The effect of three different conditioning temperatures and two methods of hanging posture on texture and palatability were assessed on leg muscles. Corresponding muscles from freshly slaughtered ewes were used as a control. A significant reduction was brought about in shear force in SM and BF muscles by different treatment combinations as compared with the control. There was, however, little variation in cohesiveness between treated and untreated BF and ST muscles. Holding carcasses at 14-15 degrees C for 24 h, followed by chilling at 4-5 degrees C for 24 h with pelvic hanging reduced shear values to the optimal level, as validated by sensory tenderness/toughness. The sensory parameters showed a significant difference between pelvic and Achilles tendon hanging. In all treatments pelvic hanging tenderised meat to a significantly greater extent than did Achilles tendon hanging. PMID- 22054988 TI - Feeder cattle frame size, muscle thickness and subsequent beef carcass characteristics. AB - Sixty feeder steers were assigned scores for frame size (small, medium or large) and muscle thickness (No. 1, No. 2 or No. 3), fed for 112 days and slaughtered. Grade data were collected for all 60 carcasses; 12 sides (four from each muscle thickness group) were fabricated into boneless, closely trimmed retail cuts and the 12 rounds from each of these sides were also physically separated into muscle, fat and bone. Marbling score and USDA quality grade varied inversely (P < 0.05) with frame size. Carcass quality grades were: 33.3% Choice; 67.7% Good and 0.0% Standard for small-framed cattle; 30.3% Choice, 42.4% Good and 27.3% Standard for medium-framed cattle and 5.5% Choice, 66.7% Good and 27.8% Standard for large-framed cattle. Analysis of variance showed significant (P < 0.05) differences among all muscle thickness groups in the longissimus muscle area and carcass weight but no difference in yield grade between the No. 1 and No. 3 muscle thickness groups; the larger mean longissimus muscle area of carcasses from steers in the No. 1 muscle thickness group was offset by their heavier carcass weight and their greater thickness of fat over the longissimus muscle. However, when analysis of covariance was used to hold fatness or fatness and frame size constant, the difference in yield grade between muscle thickness groups No. 1 and No. 3 was significant (P < 0.05). Also, carcasses from cattle assigned muscle thickness scores of No. 1, as feeders, had the highest (P < 0.05) muscle to bone ratio of the round (4.1 to 1) while carcasses from cattle assigned thickness scores of No. 3, as feeders, had the lowest (P < 0.05) muscle to bone ratio of the round (3.4 to 1). PMID- 22054989 TI - Growth and development of water buffalo and Friesian crossbred cattle, with special reference to the 'entire' and 'boneless' cuts. AB - Twelve buffaloes, nine Friesian * Baladi and nine Friesian * (Friesian * Baladi) bulls were slaughtered over the live weight ranges 161-560 kg for buffaloes and 176-448 kg for cattle. Right sides of all carcasses were jointed and dissected and the increase in the weight of 'entire' and 'boneless' cuts and cut groups (i.e. pistol; BLRC) relative to the 'entire' and 'boneless' side weights, respectively, were examined using covariance analyses. Increasing distoproximal and dorsoventral growth gradients were found in both species. Most noticeably, the sticking was early developing in buffaloes and late developing in cattle, whereas the shortloin developed approximately at an average rate in buffaloes and at a lower rate in cattle. Statistically significant but relatively slight differences were recorded between buffaloes and cattle in the adjusted means of the 'entire' and 'boneless' hind shank, sirloin (favouring buffaloes) and brisket (favouring cattle). Buffaloes were superior to cattle in weight of pistol. At an equal side weight of 73 kg buffaloes had significantly higher weight of pistol (maximum difference = 1.4 kg). At a 115 kg side weight, the maximum difference in 'entire' and 'boneless' pistol reached 3.58 and 5.04 kg, respectively. PMID- 22054990 TI - Electroencephalographic studies of stunning and slaughter of sheep and calves part 2: The onset of permanent insensibility in calves during slaughter. AB - The time of onset of permanent insensibility, subsequent to incision of the major blood vessels of the neck, was studied in eight one-week-old calves. Insensibility was determined from the study of electroencephalograms (EEG). Apart from one animal in which insensibility first occurred within 34 s, the first indication of insensibility did not occur until between 65 and 85 s. All animals subsequently showed evidence of periodic resurgence of possible sensibility for up to 123 to 323s after slaughter. Such resurgences were seen to be preceded by a respiratory gasp. The EEG did not become isoelectric until between 132 and 336 s. Involuntary movements of the animal and the presence of corneal and palpebral reflexes persisted for up to 300 s after slaughter. It is suggested that the marked increase in the time for insensibility to occur after slaughter in calves, compared with sheep and lambs, is due to a greater contribution of blood to the brain by the vertebral arteries in calves. PMID- 22054991 TI - A comparison of the meat properties of pasture-fed steers, heifers, pregnant heifers and spayed heifers. AB - Mean ultimate pH values, sarcomere lengths, cooking losses, Warner-Bratzler peak shear values and compression values for the M. longissimus dorsi (LD) did not differ significantly between heifers, spayed heifers, heifers fitted with a HEIGRO(TM) device(*) pregnant heifers (2 to 6 months pregnant) and steers, killed at 18 or 22 months of age, with mean carcass weights of 189 and 221 kg, respectively. This result, from animals grazed at pasture, agrees with those of others who used LD samples from lot-fed animals. It would appear that carcasses of non-pregnant heifers, spayed heifers, pregnant heifers, heifers fitted with a HIEGRO(TM) device and steers of similar age and subcutaneous fat depth, do not need to be differentiated on grounds of tenderness. PMID- 22054992 TI - Comparison of some properties of beef from animals homozygous or heterozygous for muscular hypertrophy. AB - Carcass characteristics and meat properties of fifty-eight steers and heifers heterozygous (M +) for muscular hypertrophy were compared with those of fifteen homozygous (M M) steers and heifers. The M M animals had a greater carcass weight (173 versus 162 kg) and killing-out percentage than M+ animals. Age at slaughter (298 days for M M and 304 for M +) and liveweights (280 kg, M M, versus 287 kg) did not differ significantly. Carcasses from M M animals were significantly shorter, with a greater eye-muscle area and thinner subcutaneous fat cover over the loin, than those from M + animals. M. semitendinosus (ST) muscles had similar sarcomere lengths, ultimate pH values and weight losses during cooking-80 degrees C for 90 min-for M M and M + animals. Adhesion values, both peak force and work done, were less for ST samples from M M than M + animals, indicating that the ST of M M animals was potentially more tender. This, and other work, suggests that the mechanical properties of cooked ST samples of M+ animals are intermediate between those of M M and + + animals with the ST of M M animals being the most tender. No dark-cutting, high ultimate pH (>6.0) samples were found in the fifteen M M animals slaughtered commercially in the present experiment. PMID- 22054993 TI - Butchering, processing and preservation of meat-Cattle, hogs, sheep, game, fish Frank G. Ashbrook. Van Nostrand Reinhold, New York, 1981. Price: L10.15. PMID- 22054994 TI - Effect on intraocular pressure in patients receiving unilateral intravitreal anti vascular endothelial growth factor injections. AB - PURPOSE: We assessed the frequency and predictive factors related to intraocular pressure (IOP) elevation in neovascular age-related macular degeneration (AMD) patients undergoing unilateral intravitreal ranibizumab and/or bevacizumab injections. DESIGN: Retrospective cohort study. PARTICIPANTS: Charts of 207 patients with neovascular AMD who presented to a single physician at a retinal referral practice over a 6-month period were retrospectively reviewed. METHODS: Data recorded included demographic information, clinical findings, total number of bevacizumab and ranibizumab injections received and IOP at each visit. Increases above baseline IOP of >5, >10, or >15 mmHg on >=2 consecutive visits while under treatment were noted. MAIN OUTCOME MEASURES: The frequency of IOP elevation was compared between treated and untreated eyes. In addition, among treated eyes, frequency and odds ratio of experiencing IOP elevation >5 mmHg above baseline on >=2 consecutive visits was stratified by number of injections. For the main regression analysis, the outcome variable was IOP elevation >5 mmHg on >=2 consecutive visits and the main independent variable was total number of injections. RESULTS: On >=2 consecutive visits, 11.6% of treated versus 5.3% of untreated/control eyes experienced IOP elevation of >5 mmHg. The mean number of injections was higher in those with (24.4; 95% confidence interval [CI], 20.9 28.0; range, 9-39) than without IOP elevation of >5 mmHg (20.4; 95% CI, 18.9 21.8; range, 3-48) on >=2 consecutive visits. There was an increased odds ratio (5.75; 95% CI, 1.19-27.8; P = 0.03) of experiencing IOP elevation >5 mmHg on >=2 consecutive visits in patients receiving >=29 injections compared with <=12 injections. Of the factors considered, only the total number of injections showed a statistically significant association with IOP elevation >5 mmHg above baseline on >=2 consecutive visits in treated eyes (P = 0.05). CONCLUSIONS: A greater number of intravitreal anti-vasular endothelial growth factor injections is associated with an increased risk for IOP elevation >5 mmHg on >=2 consecutive visits in eyes with neovascular AMD receiving intravitreal ranbizumab and/or bevacizumab. PMID- 22054995 TI - Correlation between preoperative biometry and posterior chamber phakic Visian Implantable Collamer Lens vaulting. AB - OBJECTIVE: To evaluate (1) the effect of preoperative biometric factors on vault error and (2) the difference in achieved vault (AV) and expected vault (EV) after Visian Implantable Collamer Lens (ICL) implantation. DESIGN: Retrospective, comparative, interventional case series. PARTICIPANTS: A total of 129 eyes of 75 myopic patients treated with ICL. METHODS: On the basis of the hypothesis that ICL vaulting is due mainly to an inequality between ICL size and the horizontal sulcus-to-sulcus distance (STS) or horizontal white-to-white distance (WTW), we assumed that EV would linearly correlate with ICL horizontal compression, as demonstrated in an ex vivo experiment. Expected vault was defined as follows: EV(WTW[or STS]) = (ICL size - WTW[or STS]) * 1100 MUm. With the use of preoperative data as independent variables (including age, anterior chamber depth measured from the central corneal endothelium to the anterior lens capsule, STS, WTW, ICL size, ICL size - STS, ICL size - WTW, STS - WTW, ICL diopter, and mean K reading), a multiple regression analysis was performed to evaluate meaningful factors affecting AV. MAIN OUTCOME MEASURES: Preoperative ICL EV and postoperative ICL AV. RESULTS: Mean AV was 518.6 (standard deviation [SD] 258.4 MUm). The EV(WTW) was 626.6 (SD 220.9 MUm), and EV was 242.8 (SD 364.2 MUm). Higher ICL compression tended to result in a lower AV than EV, whereas lower ICL compression tended to result in a higher AV than EV. The ICL size - STS was more highly correlated with AV than the ICL size - WTW (Pearson correlation coefficient 0.425 vs. 0.247). Stepwise multivariate regression showed that, in order of the strength of the contribution, ICL size - STS, ICL size, age, and K reading were significant factors associated with AV (adjusted R(2)=0.369), but ICL size - WTW was not. Among the meaningful factors, ICL size - STS, ICL size, and K-reading were positively correlated with AV, whereas age was negatively correlated. CONCLUSIONS: The ICL vaulting based on only the horizontal compression could not be quantitatively predicted. Additional factors, such as vertical compression by the iris, dampening effect of the ciliary sulcus structure, or innate ICL vault, should be considered to avoid unexpected vaulting after ICL implantation. PMID- 22054996 TI - Anophthalmos, microphthalmos, and Coloboma in the United kingdom: clinical features, results of investigations, and early management. AB - PURPOSE: To describe the clinical features of children with anophthalmos, microphthalmos, and typical coloboma (AMC). DESIGN: Descriptive, observational, cross-sectional study of the United Kingdom. PARTICIPANTS: A total of 135 children with AMC newly diagnosed over an 18-month period beginning in October 2006. METHODS: Cases were identified using active surveillance through an established ophthalmic surveillance system. Eligible cases were followed up 6 months after first notification. MAIN OUTCOME MEASURES: Phenotypic characteristics, both ocular and systemic, clinical investigations, causes, and interventions. RESULTS: A total of 210 eyes (of 135 children) were affected by AMC, of which 153 had isolated coloboma or coloboma with microphthalmos. The most common colobomatous anomaly was a chorioretinal defect present in 109 eyes (71.2%). Some 44% of children were bilaterally visually impaired. Systemic abnormalities were present in 59.7% of children, with craniofacial anomalies being the most common. Children with bilateral disease had a 2.7 times higher odds (95% confidence interval, 1.3-5.5, P = 0.006) of having systemic involvement than unilaterally affected children. Neurologic imaging was the most frequent investigation (58.5%) performed. Less than one third (30.3%) of the children with microphthalmos had ocular axial lengths measured. Eight children had confirmed genetic mutations. Approximately half (49.2%) of the children required ocular intervention. CONCLUSIONS: Colobomatous defects were the most common phenotype within this spectrum of anomalies in the United Kingdom. The high frequency of posterior segment colobomatous involvement means that a dilated fundal examination should be made in all cases. The significant visual and systemic morbidity in affected children underlines the importance of a multidisciplinary approach to management. PMID- 22054998 TI - The kinetics of rigor onset in beef muscle fibres. AB - Force and stiffness were investigated as beef muscle fibre preparations entered rigor mortis. The results show that single fibres enter rigor rapidly (exhibit a small t(10-90)) whilst fibre bundles exhibit a much slower rate of entry into rigor (larger t(10-90)). The mean 'rigor time' in both cases is, however, similar. The difference in kinetics is probably due to the fact that individual fibres within a bundle enter rigor at different times. Effectively anaerobic fibre bundles treated with iodoacetate exhibit a t(10-90) almost as short as do single fibres when similarly treated, suggesting that much of the inferred heterogeneity of response amongst fibres in a bundle arises from differences between fibres in the ability of glycolysis to sustain 'relaxing' concentrations of ATP. Fibres have been chemically 'skinned' after entering the rigor state. Measurements of the relationship between stiffness and tension in the skinned fibres indicate that there are two readily distinguishable rigor 'states' depending upon whether rigor is entered from the relaxed of from the contracting state. By contrast, the rigor state achieved by intact fibres is similar to that attained in skinned fibres via the contracted state, suggesting that the 'natural' rigor state is preceded by a calcium-activated contraction. Interconversion of the two rigor states generated in vitro requires an intermediary relaxed state. PMID- 22054997 TI - Long-term results of deep anterior lamellar versus penetrating keratoplasty. AB - OBJECTIVE: To compare deep anterior lamellar keratoplasty (DALK) with penetrating keratoplasty (PK) in eyes with corneal diseases not involving the corneal endothelium (keratoconus, scars after infectious keratitis, stromal dystrophies, and trauma). DESIGN: Retrospective, comparative case series. PARTICIPANTS: One hundred forty-two consecutive DALK (DALK group; big-bubble technique or manual lamellar dissection using a slitlamp) and 142 matched PK (PK group). METHODS: Three models were used to describe the postoperative outcomes of the endothelial cell density. A joint regression model was used to predict long-term graft survival. Visual acuity, ultrasound pachymetry, specular microscopy, and optical coherence tomography (OCT) findings were recorded. MAIN OUTCOME MEASURES: Postoperative endothelial cell loss and long-term predicted graft survival. RESULTS: The average 5-year postoperative endothelial cell loss was -22.3% in the DALK group and -50.1% in the PK group (P<0.0001). The early- and late-phase annual rates of endothelial cell loss were -8.3% and -3.9% per year, respectively, in the DALK group and -15.2% and -7.8% per year in the PK group (P<0.001; biphasic linear model). The median predicted graft survival was 49.0 years in the DALK group and 17.3 years in the PK group (P<0.0001). The average visual acuity was lower in the manual dissection subgroup compared with the PK group (average difference, 1.0 to 1.8 line) and with the big-bubble subgroup (average difference, 2.2 to 2.5 lines). The average central corneal thickness at 12 months was 536 MUm in the PK group, 523 MUm in the big-bubble subgroup, and 562 MUm in the manual dissection subgroup (P<0.001). The average thickness of the residual recipient stroma measured by OCT was 87+/-26 MUm in the manual dissection subgroup. No correlation was found between this figure and logarithm of the minimal angle of resolution at any postoperative time point (P>0.05). CONCLUSIONS: Long-term, model-predicted graft survival and endothelial densities are higher after DALK than after PK. The big-bubble technique gives better results than manual dissection and PK. Compared with PK, manual dissection provides higher survival of both the corneal endothelium and graft, but lower visual acuity. PMID- 22054999 TI - The quantitative analysis of fat and protein in meat by transmission infrared analysis. AB - Transmission infrared analysis, which has been successfully applied to milk analysis, was assessed for the quantitative analysis of fat and protein in meat products. Meats of varying fat and protein content were converted into milk-like emulsions, which were, in turn, analyzed by standard chemical methods and by a Multispec M infrared analyzer. The performance of the instrument for meat analysis using a standard milk calibration was also assessed and compared with the instrument set with a meat calibration. Both approaches provided a good estimate of the fat and protein content for a range of meat products, the meat calibration being more accurate than the milk calibration. The infrared method allowed for rapid and accurate analysis of meat and has future potential in the meat industry for quality control purposes. PMID- 22055000 TI - Modification of the heat-setting characteristics of myosin by pressure treatment. AB - The effect on the heat-setting characteristics of myosin of pressure treatment up to 150 MPa at 0 to 40 degrees C has been assessed by measuring the work done in inserting a plunger into samples after heating them at up to 70 degrees C. The response depended upon the ionic strength and the pH of the myosin suspension, and the intensity and duration of pressure treatment. It was most pronounced at pressures of 75 MPa or greater applied for some minutes to myosin in 0.2-0.3m NaCl at about pH 6. It is suggested that the alteration in heat-setting properties is due to depolymerization, under pressure, of myosin filaments accompanied by a conformational change of the monomer so that it reaggregates in a different manner upon release of pressure. PMID- 22055001 TI - Effect of lipid-protein interactions on extrusion of offal protein isolates. AB - Lung protein isolates after defatting with carbon tetrachloride, chloroform, dichloromethane, iso-propanol, ethanol and methanol, were extruded with and without admixed soya grits. Extrusion of these isolates showed a clear dependence of the process on the lipid content. Extruded products with better characteristics were obtained by defatting the samples. Progressive removal of lipid, as the polarity of the solvent used increased, however, did not promote a corresponding progressive improvement in the textural quality of the extrudates. Protein-protein interaction was assessed by the primary mechanical parameters, hardness, springiness and cohesiveness. It was maximal at intermediate lipid contents. These broadly corresponded to the range of lipid contents where maximum hydration and affinity towards water occurred. It was concluded that residual lipid is necessary in order to maximize protein-protein interactions during extrusion. The effects of lipid-protein interactions on the texturization of offal protein caused a wide variation in the degree of cross-linking between protein molecules during extrusion. The results showed that hydrophobic and electrostatic interactions can play an important role in texture formation during thermoplastic extrusion. PMID- 22055002 TI - Differential effects of electrical stunning on the early post-mortem glycolysis in sheep. AB - Electrical stunning methods have been examined to determine the effect on post mortem glycolysis in various muscles of sheep. Although there was no effect on the ultimate pH achieved in any of the muscles, there were marked differences in the pH drop which occurred during stunning. When curare was used to block neuromuscular transmission much of the effect of stunning on glycolysis was removed. In the absence of neuromuscular blockage, head-only stunning produced the least drop in initial pH and the head-to-back and head-to-foreleg methods the greatest drop, especially in the anterior portions of the LD. Gash cutting without prior stunning produced marked drops in pH in most muscles. Prolonged (120s) head-to-back stunning gave more substantial drops in pH in the LD, BF, SM and ST muscles than did a shorter stun (1.4s). The prolonged stunning did not produce a change in rate of pH fall. Electrical stunning cannot be considered as a substitute for effective electrical stimulation as a means of hastening glycolysis to avoid cold shortening. PMID- 22055003 TI - Biophysical methods in food research Edited by H. W.-S. Chan. Blackwell Scientific Publications, Oxford, 1984. 204 + vii pp. Price: L19.50. PMID- 22055004 TI - The development of silk fibroin scaffolds using an indirect rapid prototyping approach: morphological analysis and cell growth monitoring by spectral-domain optical coherence tomography. AB - To date, naturally derived biomaterials are rarely used in advanced tissue engineering (TE) methods despite their superior biocompatibility. This is because these native materials, which consist mainly of proteins and polysaccharides, do not possess the ability to withstand harsh processing conditions. Unlike synthetic polymers, natural materials degrade and decompose rapidly in the presence of chemical solvents and high temperature, respectively. Thus, the fabrication of tissue scaffolds using natural biomaterials is often carried out using conventional techniques, where the efficiency in mass transport of nutrients and removal of waste products within the construct is compromised. The present study identified silk fibroin (SF) protein as a suitable material for the application of rapid prototyping (RP) or additive manufacturing (AM) technology. Using the indirect RP method, via the use of a mould, SF tissue scaffolds with both macro- and micro-morphological features can be produced and qualitatively examined by spectral-domain optical coherence tomography (SD-OCT). The advanced imaging technique showed the ability to differentiate the cells and SF material by producing high contrasting images, therefore suggesting the method as a feasible alternative to the histological analysis of cell growth within tissue scaffolds. PMID- 22055005 TI - End of life care in adolescents and young adults with cancer: experience of the adolescent unit of the Institut Gustave Roussy. AB - BACKGROUND: Cancer is the third leading cause of death in adolescents and young adults (AYA). Little is known, however, about how end-of-life unfolds for those who die of progressive disease. In order to better evaluate the specific needs of these patients, we performed this study providing baseline information about end of-life care patterns for AYA in our department. PATIENTS: A standardised form was used to collect data concerning all 45 patients treated for a malignancy in the Paediatric and Adolescent Oncology Department at the Gustave Roussy Institute, and who had died of progressive disease above 13 years of age, over a two-year period. RESULTS: The main diagnoses were sarcomas and brain tumours. Previous cancer-directed treatment included a median of 3 different chemotherapy regimens, high-dose chemotherapy with haematopoietic stem cell support for 13% and radiotherapy for 40%. One in every four patients had been enrolled in a clinical trial at diagnosis. Median survival was 18 months after the diagnosis and 7 months after the first relapse/progression. During the last week of life, the median number of physical symptoms was 4, mostly pain and dyspnoea. Frequent psychological symptoms were sadness, anxiety, fear and guilt. End-of-life care included transfusions, artificial nutrition, corticosteroids, pain control, sedation but also palliative chemotherapy. The median time spent in hospital during the last month of life was 16 days. Most patients had died in hospital. CONCLUSIONS: The terminally ill adolescent displays notable challenges to care providers and requires a holistic approach with the help of a multidisciplinary team. PMID- 22055006 TI - Thoracic paravertebral block for video-assisted thoracoscopic surgery: single injection versus multiple injections. AB - OBJECTIVE: Thoracic paravertebral blocks (PVBs) have been shown to be effective for analgesia after video-assisted thoracoscopic surgery (VATS) with single- and multiple-injection techniques. The efficacy of single-injection PVB was compared with multiple-injection PVB on postoperative analgesia in VATS was studied. DESIGN: Prospective, randomized study. SETTING: Single university hospital. PARTICIPANTS: Fifty patients undergoing VATS. INTERVENTIONS: A nerve stimulator guided PVB was performed in the sitting position before surgery using a solution of 20 mL 0.5% bupivacaine with 1:200,000 epinephrine by a single injection at T6 (group S, n = 25) or by 5 injections of 4 mL each at T4 to T8 (group M, n = 25). MEASUREMENTS AND MAIN RESULTS: A successful PVB was achieved in all patients. The times to perform the blocks were 6.8 +/- 1.9 minutes in the S group and 17.9 +/- 3.0 minutes in the M group (p < 0.001). The times to block onset were 8.3 +/- 1.8 minutes in the S group and 7.2 +/- 0.9 minutes in the M group (p = 0.014). The numbers of anesthetized dermatomes were 5.8 +/- 0.8 for the S group and 6.6 +/- 1.1 for the M group (p = 0.009). The postoperative pain scores and morphine consumption with patient-controlled analgesia were comparable in the two groups. There were no significant differences in times to the first mobilization and hospital discharge for two groups. Patient satisfaction with the analgesic procedure was greater in the S group (p < 0.05). No complications were attributed to the blocks. CONCLUSIONS: The two techniques provided comparable postoperative analgesia. However, single-injection PVB may represent an advantage over multiple injection PVB in patients undergoing VATS, with greater patient satisfaction associated with a shorter procedure and the likelihood of decreased complications. PMID- 22055007 TI - Removal of a foreign body from the heart under transesophageal echocardiographic guidance. PMID- 22055008 TI - Extracorporeal membrane oxygenation implantation via median sternotomy for fulminant pulmonary edema after cold water submersion with cardiac arrest. PMID- 22055009 TI - Anesthesia for interventional cardiology. PMID- 22055010 TI - Carisoprodol tolerance and precipitated withdrawal. AB - AIMS: Carisoprodol is a muscle relaxant that acts at the GABA(A) receptor. Concerns about the abuse liability of carisoprodol are increasing, but evidence that carisoprodol produces tolerance and a significant withdrawal syndrome has yet to be established. The purpose of the current study was to determine if repeated administration of carisoprodol produces tolerance and withdrawal signs in a mouse model. METHODS: Carisoprodol (0, 100, 200, 300, or 500 mg/kg bid, i.p.) was administered to Swiss-Webster mice for 4 days and loss-of-righting reflex was measured 20-30 min following each administration. On the fourth day, bemegride (20 mg/kg), flumazenil (20 mg/kg), or vehicle was administered following carisoprodol and withdrawal signs were measured. Separate groups of mice receiving the same treatment regimen and dose range were tested for spontaneous withdrawal at 6, 12 and 24 h after the last dose of carisoprodol. RESULTS: The righting reflex was dose-dependently impaired following the first administration of carisoprodol. A 75-100% decrease in the magnitude of the impairment occurred over the four days of exposure, indicating the development of tolerance to the carisoprodol-elicited loss-of-righting reflex. Withdrawal signs were not observed within 24h following spontaneous withdrawal; however, bemegride and flumazenil each precipitated withdrawal within 15-30 min of administration. CONCLUSIONS: Carisoprodol treatment resulted in tolerance and antagonist precipitated withdrawal, suggesting it may have an addiction potential similar to that of other long-acting benzodiazepine or barbiturate compounds. PMID- 22055011 TI - The Physicians' Competence in Substance Abuse Test (P-CSAT): a multidimensional educational measurement tool for substance abuse training programs. AB - BACKGROUND: Efforts to enhance physician substance abuse (SA) management skills lack tools to assess skills and training effectiveness. We sought to develop an easily administered survey to assess SA fact-based skills and clinical decision making. METHODS: We prepared 60 fact-based items dealing with SA knowledge, attitudes, and behaviors (KAB) and 53 script concordance test (SCT) items assessing SA decision-making. We used expert review and standard psychometric criteria to eliminate discordant or non-contributory survey items. We tested 92 draft items in 117 physicians, including 13 with additional SA training (trained), and 17 recognized SA experts. We assessed final survey internal consistency with Cronbach's alpha and differences in scores between experts, trained physicians, and physicians without SA training (novices) with the Kruskal Wallis test. RESULTS: Following refinement, the draft survey was reduced to 30 KAB and 33 SCT items. Alpha was 0.901 for the final 63-item survey and 0.887 and 0.797 for the KAB and SCT subscales, respectively. Novices, trained physicians, and experts scored means of 196, 213, and 261 respectively out of 315 possible points on the final survey. The KAB and SCT subscale results showed similar patterns. Score differences for the overall survey and its subscales were highly significant (p<0.001). CONCLUSIONS: This survey, which we have named the Physicians' Competence in Substance Abuse Test (P-CSAT) and placed in the public domain, meets baseline criteria for reliability and validity. Future studies should determine the extent to which the P-CSAT provides consistent results in other practitioner populations and responds to SA educational efforts. PMID- 22055012 TI - The Sexual Discounting Task: HIV risk behavior and the discounting of delayed sexual rewards in cocaine dependence. AB - BACKGROUND: Cocaine dependence is associated with high rates of sexual risk behavior and HIV infection. However, little is known about the responsible mechanism(s). METHODS: Cocaine-dependent individuals (N=62) completed a novel Sexual Discounting Task assessing decisions between immediate unprotected sex and delayed sex with a condom across four hypothetical partners: most (and least) likely to have a sexually transmitted infection (STI), and most (and least) sexually desirable; a real rewards money delay-discounting task, and self reported sexual risk behavior using the HIV Risk-Taking Behavior Scale (HRBS). RESULTS: Sexual Discounting Task results were largely systematic and showed a strong effect of delay in decreasing condom use. Sexual discounting (preference for immediate unprotected sex) was significantly greater when making responses for partners judged least (compared to most) likely to have an STI, and for partners judged most (compared to least) desirable. Differences in sexual discounting were significant after controlling for differences in condom use (with no delay) between conditions. Greater discounting in 3 of the 4 Sexual Discounting Task conditions, but not in the money discounting task, was associated with greater self-reported sexual risk behavior as measured by the HRBS. CONCLUSIONS: Results suggest that delay is a critical variable strongly affecting HIV sexual risk behavior, and that the Sexual Discounting Task provides a clinically sensitive measure of this phenomenon that may address a variety of questions about HIV risk in future research. The wealth of behavioral and neurobiological data on delay discounting should be brought to bear on HIV education and prevention. PMID- 22055013 TI - Heart rate turbulence during acute alcohol withdrawal syndrome. AB - BACKGROUND: Alcohol withdrawal syndrome is associated with an increased incidence of cardiac arrhythmias and sudden cardiac death. Heart rate turbulence (HRT) parameters were applied during withdrawal to estimate cardiac regulation during treatment with clomethiazole. METHODS: Twenty-two patients suffering from alcohol withdrawal syndrome were included in the study. Heart rate regulation was obtained by means of Holter ECG analyzing time intervals before medication, and 2 and 6h after medication. Slope and onset of HRT were calculated in addition to heart rate variability (HRV) parameters. Furthermore, we calculated the slope and the onset of ectopic beat-like events. RESULTS: Heart rate variability parameters indicated a minor reduction of vagal modulation during withdrawal syndrome. Especially, the fractal scaling exponent BBI alpha1 (4-16) indicated the autonomic shift. In contrast to HRV parameters, no significant changes were observed in the HRT parameters. Significant correlations were observed between severity of withdrawal, as assessed by the AWS scale, and the fractal scaling exponent BBI alpha2 (16-64), and the onset and the slope of HRT of ectopic beat like activity. CONCLUSION: Increased sympathetic modulation during withdrawal and clomethiazole treatment is not associated with changes of heart rate turbulence parameters predictive of cardiac death after myocardial infarction. PMID- 22055014 TI - Differential role of NR2A and NR2B subunits in N-methyl-D-aspartate receptor antagonist-induced aberrant cortical gamma oscillations. AB - BACKGROUND: N-methyl-D-aspartate receptor (NMDA-R) hypofunction plays an important role in cognitive impairment in schizophrenia. NMDA-R antagonists elicit psychotic symptoms in humans and schizophrenia-relevant signs in rodents, including a strong increase in cortical gamma activity. NMDA-Rs are composed of different subunits, and accumulating evidence indicates that neuronal damage due to NMDA-R antagonists depends on their action on a specific type of the receptor containing the NR2A subunit. In human schizophrenics, NR2A is selectively reduced in fast-firing interneurons. These neurons are critical for gamma oscillations, indicating that pathological changes in gamma activity may depend on subunit specific NMDA-R deficit. The present study tested this hypothesis. METHODS: Cortical electroencephalograms were recorded in freely moving rats and the changes in gamma power were measured after administration of NMDA-R antagonists with different subunit selectivity, including NR2A-preferring (PEAQX, n = 5; NVP AAM077, n = 18), NR2B-selective (ifenprodil, n = 6; threo-ifenprodil, n = 4; Ro25 6985, n = 13), and NR2C/D-selective (n = 8) antagonists, along with vehicle and nonselective NMDA-R antagonists (ketamine, n = 10; MK801, n = 12). Changes in prepulse inhibition of startle was tested after MK-801 (n = 6), NVP-AAM077, and Ro-6891 (n = 5) injection. RESULTS: Strong increase in gamma power was induced by nonselective NMDA-R antagonists and by blockade of NMDA-Rs containing the NR2A subunit, with co-occurring gating deficits and diminished low-frequency modulation of gamma oscillations. In contrast, selective blockade of NR2B, C, or D subunit-containing receptors had minor effects. CONCLUSIONS: Major subtype specific differences in the role of NMDA-Rs in cortical gamma oscillation may have implications for the pathomechanism and treatment of cognitive impairment in schizophrenia. PMID- 22055015 TI - Multiple biological pathways link cognitive lifestyle to protection from dementia. AB - BACKGROUND: An active cognitive lifestyle is linked to diminished dementia risk, but the underlying mechanisms are poorly understood. Potential mechanisms include disease modification, neuroprotection, and compensation. Prospective, population based brain series provide the rare opportunity to test the plausibility of these mechanisms in humans. METHODS: Participants came from the United Kingdom Medical Research Council Cognitive Function and Ageing Study, comprising 13,004 individuals aged over 65 years and followed for 14 years. In study 1, a Cognitive Lifestyle Score (CLS) was computed on all Cognitive Function and Ageing Study subjects to define low, middle, and high groups. By August 2004, 329 individuals with CLS data had come to autopsy and underwent Consortium to Establish a Registry of Alzheimer's Disease assessment. Study 2 involved more detailed quantitative histology in the hippocampus and Brodmann area 9 in 72 clinically matched individuals with high and low CLS. RESULTS: CLS groups did not differ on several Alzheimer disease neuropathologic measures; however, high CLS men had less cerebrovascular disease after accounting for vascular risk factors, and women had greater brain weight. No group differences were evident in hippocampal neuronal density. In Brodmann area 9, cognitively active individuals had significantly greater neuronal density, as well as correlated increases in cortical thickness. CONCLUSIONS: An active cognitive lifestyle was associated with protection from cerebrovascular disease in men, but there was no evidence for Alzheimer disease modification or hippocampal neuroprotection. Men and women both exhibited neurotrophic changes in the prefrontal lobe linked to cognitive lifestyle, consistent with a compensatory process. Lifespan complex cognitive activity may therefore protect against dementia through multiple biological pathways. PMID- 22055016 TI - Intact relational memory and normal hippocampal structure in the early stage of psychosis. AB - BACKGROUND: Previous studies indicate that the transition to psychosis is associated with dynamic changes of hippocampal integrity. Here we explored hippocampal volume and neural activation during a relational memory task in patients who were in the early stage of a psychotic illness. METHODS: Forty-one early psychosis patients and 34 healthy control subjects completed a transitive inference (TI) task used previously in chronic schizophrenia patients. Participants learned to select the "winner" of two sets of stimulus pairs drawn from an overlapping sequence (A > B > C > D > E) and a nonoverlapping set (a > b, c > d, e > f, g > h). During a functional magnetic resonance imaging scan, participants were tested on the trained pairs and made inferential judgments on novel pairings that could be solved based on training (e.g., B vs. D). Hippocampal volumes were manually segmented and compared between groups. Functional magnetic resonance imaging analyses included 27 early psychosis patients and 30 control subjects who met memory training criteria. RESULTS: Groups did not differ on inference performance or hippocampal volume and exhibited similar activation of medial temporal regions when judging nonoverlapping pairs. However, patients who failed to meet memory training criteria had smaller hippocampal volumes. Neural activity during TI was less widespread in early psychosis patients, but between-group differences were not significant. Hippocampal activity during TI was positively correlated with inference performance only in control subjects. CONCLUSIONS: Our results provide evidence that relational memory impairment and hippocampal abnormalities, well established in chronic schizophrenia, are not fully present in early psychosis patients. This provides a rationale for early intervention, targeting the possible delay, reduction, or prevention of these deficits. PMID- 22055017 TI - Phasic nucleus accumbens dopamine encodes risk-based decision-making behavior. AB - BACKGROUND: To optimize behavior, organisms evaluate the risks and benefits of available choices. The mesolimbic dopamine (DA) system encodes information about response costs and reward delays that bias choices. However, it remains unclear whether subjective value associated with risk-taking behavior is encoded by DA release. METHODS: Rats (n = 11) were trained on a risk-based decision-making task in which visual cues predicted the opportunity to respond for smaller certain (safer) or larger uncertain (riskier) rewards. Following training, DA release within the nucleus accumbens (NAc) was monitored on a rapid time scale using fast scan cyclic voltammetry during the risk-based decision-making task. RESULTS: Individual differences in risk-taking behavior were observed as animals displayed a preference for either safe or risky rewards. When only one response option was available, reward predictive cues evoked increases in DA concentration in the NAc core that scaled with each animal's preferred reward contingency. However, when both options were presented simultaneously, cue-evoked DA release signaled the animals preferred reward contingency, regardless of the future choice. Furthermore, DA signaling in the NAc core also tracked unexpected presentations or omissions of rewards following prediction error theory. CONCLUSIONS: These results suggest that the dopaminergic projections to the NAc core encode the subjective value of future rewards that may function to influence future decisions to take risks. PMID- 22055018 TI - Short telomeres in depression and the general population are associated with a hypocortisolemic state. AB - BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in stress regulation, and leukocyte telomere length (TL) has been suggested to represent a cumulative measure of stress. Depression is intimately related with stress and frequently exhibits a dysregulated HPA axis. We aimed to study the relationships between TL and biological and psychological facets of stress in recurrent major depressive disorder and controls. METHODS: Leukocyte TL was measured in 91 subjects with recurrent major depressive disorder and 451 control subjects. Stress was assessed from both a biological perspective, by assessing HPA axis function with a weight-adjusted very-low-dose dexamethasone suppression test (DST), and a psychological perspective, with self-report questionnaires. RESULTS: TL was shorter among patients compared with control subjects (277 base pairs, p = .001). Overall, short TL was associated with a hypocortisolemic state (low post-DST cortisol and high percentage of cortisol reduction after the DST) among both patients and control subjects but more pronounced among patients. This state, which was overrepresented among patients, was characterized by high familial loading of affective disorders among patients (p = .001) and high C reactive protein levels among control subjects (p = .040). TL was also inversely associated with stress measured with the Perceived Stress Questionnaire (r(s) = .258, p = .003). CONCLUSIONS: Short TL is associated with depression and hypocortisolism. Because hypocortisolism has been shown to develop from chronic stress exposure, our findings corroborate the concept of TL as a cumulative measure of stress and provide novel insights into the detrimental role of stress in depressive illness and the general population. PMID- 22055019 TI - Poles apart: Scott, Amundsen and science. AB - One hundred years ago, teams led by Roald Amundsen and Robert Scott may have been heading in the same direction but they were poles apart in the way they sought their goals. Amundsen led a five-person team of expert Nordic skiers and dog sledders with a single goal: getting to the South Pole first. He planned and executed the effort brilliantly. Scott, in contrast, led a complex and multi faceted Antarctic expedition with 33 explorers and scientists, many of whom were focused on ambitious and often taxing scientific research projects that had nothing whatsoever to do with reaching the Pole. Although Scott failed to reach the South Pole first and died with four men on the return trip, his expedition made significant contributions to Antarctic science. Indeed, at least some of Scott's failure to reach the Pole first and the subsequent death of his polar party on the return trip can be attributed to burden of trying to do too much and not focusing on reaching the pole. PMID- 22055020 TI - Guidelines for the diagnosis and management of hereditary spherocytosis--2011 update. AB - Guidelines on hereditary spherocytosis (HS) published in 2004 (Bolton-Maggs et al, 2004) are here replaced to reflect changes in current opinion on the surgical management, (particularly the indications for concomitant splenectomy with cholecystectomy in children with mild HS, and concomitant cholecystectomy with splenectomy in those with asymptomatic gallstones). Further potential long term hazards of splenectomy are now recognised. Advances have been made in our understanding of the biochemistry of the red cell membrane which underpins the choice of tests. Biochemical assays of membranes proteins and genetic analysis may be indicated (rarely) to diagnose atypical cases. The diagnostic value of the eosin-5-maleimide (EMA) binding test has been validated in a number of studies with understanding of its limitations. PMID- 22055021 TI - The desert camel as a meat animal. AB - Fifty-two mature, fattened male camels were used for determining live animal and carcase measurements, carcase yield and characteristics. The average slaughter weight of mature, fattened desert camels was 456 kg, while the mean empty body weight was 404.8 kg. The camel carcase dressed out as 55.8% and 63.6% of live and empty body weight, respectively. The mean carcase composition was 56% meat,19% bone and 13.7% fat. Of the body components of the camel, the head, hide and liver represented 3.5, 8.6 and 2.0% of the empty body weight, respectively. The correlations between heart girth and liveweight were high and positive. The depth of the camel hump was significantly highly correlated with carcase fat and the hump fat weight had a positive high correlation (r = 0.97, P < 0.001) with carcase fat. PMID- 22055022 TI - The strength and stiffness of perimysial connective tissue isolated from cooked beef muscle. AB - Thick transverse slices of bovine M. semitendinosus were cooked for 1 h at 50 degrees -90 degrees and then cooled. Perimysial connective tissue was dissected from the cooked meat and subjected to mechanical testing in a small-scale device. The initial 'toe' region of the J-shaped load-extension curve was progressively lost with increasing temperature, the curve becoming more nearly linear after cooking at 90 degrees C. These effects are explained on the basis of the progressive straightening out of the crimps from the collagen fibres, the crimps becoming finally lost at approximately 70 degrees C. The final stiffness of the perimysium at greater extensions was unchanged at higher temperatures. Breaking strength increased from raw to cooked at 50 degrees C, thereafter decreasing at cooking temperatures up to 90 degrees C. it is proposed that this technique of testing isolated perimysium gives a valuable means of directly measuring the effects of cooking, or other treatments, on the intrinsic properties of perimysial collagenous material. Quantitative knowledge of these will help to determine its contribution to the overall mechanical properties, and hence eating quality, of cooked meat. PMID- 22055023 TI - Electron Microscopy of bovine muscle, I-The native state of post rigor sarcolemma and endomysium. AB - The bovine sarcolemma with its associated endomysium has been shown to maintain its integrity post rigor except for the occurrence of some small perforations in the sarcolemma. The close structural association of the three component parts, i.e. the plasmalemma, basement membrane and endomysium, persists even during physical disruption of muscle, such that when a tear occursall three parts are involved. PMID- 22055024 TI - Electron microscopy of bovine muscle: II-The effects of heat denaturation on post rigor sarcolemma and endomysium. AB - After 1 h at 50 degrees C the collagen fibrils of the endomysium appeared beaded, brought about by their close association with the heat denatured non-collagenous proteins in the extracellular spaces. Heat denaturation of the lipoprotein plasmalemma resulted at 60 degrees C plus for 1 h. The breakdown products of the plasmalemma, large granules, were often associated with the basement lamina, which appeared to survive intact even after 100 degrees C for 1 h. Loss of the plasmalemma and partial thermal shrinkage of the endomysial collagen at higher temperatures (70 degrees C plus) together with a probable loss of plasticity of the myofibrillar masses, resulted in frequent ruptures of the endomysial tube remains. These ruptures, which appeared during the exposure of surfaces prior to SEM observation, were not seen prior to heat treatment. PMID- 22055025 TI - Fatty acid and proximate composition of raw and cooked retail cuts of beef trimmed to different external fat levels. AB - Beef steaks and roasts from US Choice, US Select and US Standard quality grades were used to determine the effect of 0.64 cm external fat trim and zero (no external fat) trim on the proximate and fatty acid composition of cooked cuts of beef. Total fat percentage of the cooked lean was affected by external fat trim, quality grade, cooking and degree of doneness. Fat retention percentages were higher in tenderloin and clod samples when cooked with external fat attached than when cooked with no external fat. No consistent effect of fat trim level or degree of doneness on the percentage of specific fatty acids was observed. PMID- 22055026 TI - The storage life of chilled pork packaged under carbon dioxide. AB - Pork cuts of longissimus dorsi muscle with overlaying fat and skin were packed under vacuum in film of low oxygen transmission rate, or under CO(2) in gas impermeable aluminium foil laminate. Cuts were stored at +3 or -1.5 degrees C. Vacuum packaged cuts were grossly spoiled by Brochothrix thermosphacta after 2 weeks' storage at 3 degrees C and after 5 weeks at -1.5 degrees C. Cuts packaged under CO(2) were grossly spoiled by B. thermosphacta after 5.5 weeks' storage at 3 degrees C. Growth of B. thermosphacta was suppressed when CO(2) packaged cuts were stored at -1.5 degrees C. At that temperature, slow growth of enterobacteria was detected after a lag of about 18 weeks. The enterobacteria caused gross spoilage of an increasing proportion of cuts between 18 and 26 weeks. Muscle tissue with pale, soft, exudative (PSE) characteristics tended to lose colour after long storage periods, apparently because of loss of myogglobin with exudate. Until spoilage, the eating qualities of pork appeared little affected by prolonged storage. PMID- 22055028 TI - The good news about cancer in developing countries. PMID- 22055029 TI - Care for children undergoing surgery: we are not there yet. PMID- 22055030 TI - Torture in Syria's hospitals. PMID- 22055031 TI - The Lancet-University of Oslo Commission on Global Governance for Health, in collaboration with the Harvard Global Health Institute. PMID- 22055033 TI - Iodine deficiency in UK schoolgirls. PMID- 22055034 TI - Iodine deficiency in UK schoolgirls. PMID- 22055035 TI - Iodine deficiency in UK schoolgirls. PMID- 22055037 TI - 5 versus 10 days of ceftriaxone for bacterial meningitis in children. PMID- 22055038 TI - 5 versus 10 days of ceftriaxone for bacterial meningitis in children. PMID- 22055040 TI - Mandating influenza vaccination in health-care workers. PMID- 22055041 TI - Editorial code of conduct. PMID- 22055042 TI - Never too old. PMID- 22055043 TI - Lead poisoning in China. PMID- 22055045 TI - Environmental and food contamination with plasticisers in China. PMID- 22055046 TI - Arabic roots of modern medicine. PMID- 22055047 TI - Comparison of some properties of meat from normal steers and steers heterozygous for muscular hypertrophy. AB - Carcase characteristics and meat properties of 19 normal steers and 14 steers heterozygous for muscular hypertrophy (HMH), killed at a liveweight of circa 360 kg and 500 days of age, were compared. Carcases of the HMH animals had less subcutaneous fat and a greater eye muscle area. It was considered that HMH animals were no more stress susceptible than control animals as plasma glucose concentrations at slaughter and ultimate pH values of the M. semitendinosus (ST) did not differ. ST sarcomere length and cooking losses did not differ between control and HMH animals. ST Warner-Bratzler (peak) shear force values and adhesion values were less in the HMH animals; these lower values would indicate that the ST of the HMH animals was more tender. These differences may have resulted from the difference in the mean age of the normal (527 days) and the HMH groups (489 days) at slaughter. However, other workers have found a reduced hydroxyproline content in muscles of homozygous double-muscled animals and the lower adhesion values of animals heterozygous for muscular hypertrophy may reflect the fact that they also have a lower connective tissue content in their muscles compared with normal animals. PMID- 22055048 TI - Histological and shear properties of bovine muscle and their alteration during postmortem ageing. AB - A total of 108 longissimus dorsi (LD) and 37 semitendinosus (ST) bovine muscles were utilised to evaluate the cellular changes and interrelationships among histological properties during postmortem ageing. The most important cellular change during postmortem ageing in the LD was an increase in the degree of muscle fibre fragmentation (i.e. reduction in the length of muscle fibre fragments) and in the ST a combination of an increase in degree of muscle fibre fragmentation and a lengthening of the sarcomeres. Degree of muscle fibre fragmentation was the most highly and consistently related histological trait to shear force values and interrelationships of LD histological traits indicated that fibres with larger fibre diameters had shorter sarcomeres and fragmented to a lesser degree. In addition, higher incidences of wavy LD fibres were generally associated with shorter sarcomeres post rigor. In general, histological traits within the ST were interrelated only after 13 days of ageing and histological traits among muscles were generally not significantly interrelated. PMID- 22055049 TI - Influence of cooling and freezing of minced pre-rigor muscle on the breakdown of ATP and glycogen. AB - The high water-holding capacity of pre-rigor beef can be preserved for months by rapid freezing of the minced salted or unsalted bovine muscle before onset of the breakdown of ATP. If beef frozen in this way is processed without preceding thawing, sausages of excellent quality are obtained. The same result can be obtained using beef salted and freeze-dried in the pre-rigor state. It is important in both procedures to ensure that the depletion of ATP during freezing is kept to a minimum. The optimum conditions for cooling and freezing were therefore studied. If NaCl is not added, the rate of ATP breakdown decreases with falling temperature to about +6 degrees C but then increases with further cooling, reaching a maximum rate at about -1 degrees C, at which temperature the meat remains for a relatively long period during freezing. If the beef is salted, the rate of ATP hydrolysis decreases with falling temperature until the meat is frozen. Above + 3 degrees C the concentration of ATP is lower in salted than unsalted meat in the first hours post mortem, but below this temperature the position is reversed. The influence of temperature on lactate formation, i.e. on the rate of glycolysis in the presence and absence of salt, follows similar patterns. Therefore, it is better to salt the beef before freezing rather than during the preparation of the sausage emulsion. These influences of temperature on the ATP depletion in unsalted and salted beef can be explained in terms of the release of Ca(2+) ions from the sarcoplasmic reticulum. PMID- 22055050 TI - Effects of level of feeding, pre-slaughter stress and method of slaughter on postmortem glycolysis of sheep muscles. AB - Increased psychological stress, engendered in the remaining animals as each animal was taken and killed, sequentially, from a pen of four animals, decreased M. longissimus dorsi (LD) glycogen concentrations at 30 min (initial) and4.5 h postmortem and initial (12 min postmortem) M. semitendinosus (ST) pH values. Increasing stress, with order of slaughter, was associated with increased initial temperatures in both muscles. Stunned animals had lower initial temperatures in LD and ST than unstunned animals. pH values at 4.5 and 6sd5 h postmortem in the LD and at 6.5 h in the ST were greater in muscles from stunned sheep than in those from unstunned sheep. LD glycogen concentrations at 4.5 h postmortem were greater in animals receiving less feed; an effect only in part due to the faster cooling rate of their lighter, less fat carcases. Initial ST glycogen concentrations were approximately half those of initial LD glycogen concentrations. PMID- 22055051 TI - Relationships between time of stunning and time of throat cutting and their effect on blood pressure and blood splash in lambs. AB - A study based on 84 electrically stunned lambs showed that those gash stuck (transverse incision of the extended neck which almost simultaneously severs the trachea, oesophagus, common carotid arteries and jugular veins and the spinal cord at the occipito-atlantal junction; Blackmore & Newhook, 1976) immediately after removal of the electrical applicator had a lower incidence of blood splash than lambs gash stuck 5-8 sec r stunning. Lambs whose throats were cut immediately before the application of the electrical current had the lowest incidence of blood splash. None of the splash observed was of commercial significance. Systolic blood pressure recordings were made on a further 12 lambs of a similar age, 10 of which were electrically stunned and two shot with a captive bolt pistol. Blood pressure changes observed were related to the blood splash results obtained in the first trial. Electrical stunning raised blood pressures to an average of 3.5 times normal in lambs allowed to recover from stunning. A further seven young unweaned lambs which were electrically or percussion stunned showed a similar pattern of blood pressure change to that reported for older lambs following stunning, except that lower maximum pressures were reached. The authors interpret the results of the present trials as indicating that the application of electrical current to the heads of lambs results in damage to small vessels prior to the elevation of blood pressure. This damage may become apparent in the dressed carcass and organs as small haemorrhages. The subsequent rise in blood pressure following stunning then exacerbates the leakage of blood into tissues and it becomes more apparent in the form of discrete haemorrhages or blood splash. PMID- 22055052 TI - The ecology of bacterial spoilage of fresh meat at chill temperatures. AB - At chill temperatures the spoilage flora of meat is composed of psychrotrophs originating largely from the hides of slaughtered animals. Under humid conditions, aerobic floras are usually dominated by pseudomonads while anaerobic floras are dominated by lactobacilli. In both cases growth occurs on low molecular weight soluble components of meat which are attacked in the order glucose, glucose-6-phosphate (Enterobacteriaceae only) and amino acids. Under aerobic conditions spoilage becomes detectable when the bacteria begin to degrade amino acids which remain abundant at the meat surface when growth ceases, probably because of limited availability of oxygen. Under anaerobic conditions growth ceases because the diffusion of fermentable substrates to the surface is not rapid enough to support further growth. Aerobically, there is no interaction between different bacterial species until the maximum cell density is approached; anaerobically, however, lactobacilli produce an antimicrobial agent which inhibits growth of competing species. The composition of spoilage floras can be affected by changes in water activity and the storage atmosphere. PMID- 22055053 TI - Effect of restraint on the thermal transitions of tendon. AB - Sheep tendon samples that had been given a heat treatment in 0.9% sodium chloride solution at temperatures above their normal shrinkage temperature (ST) were examined by differential scanning calorimetry. If the tendon was not restrained from shrinkage during the heat treatment, no endothermic transition in the region of 60 degrees C was subsequently detected by calorimetry. If it was restrained an endothermic transition was then detected, the magnitude of which was inversely related to the shrinkage allowed to occur during heat treatment. Values for transition heat (DeltaH) and transition temperature (T(1,2)) of tendon samples restrained at their original taut length and heat treated 10 degrees -15 degrees C above the ST were similar to those found for unheated control samples. However, increase in the temperature of the heat treatment to 20 degrees -30 degrees C above the ST resulted in a decrease in both DeltaH and T(1,2) and the transition became broader. PMID- 22055054 TI - Lysosomal proteinases in muscle tissue and leukocytes of meat animals. AB - Carboxypeptidases A and B, cathepsins B, D and E, dipeptidyl aminopeptidase 1 and collagenase were extracted from bovine and porcine leukocyte lysosomes and diaphragm muscle lysosomes with 4% n-butyl alcohol in dry ice and various chemical properties were studied. The enzymes were classified by their specific activities with different substrates, pH optima, energies of activation and the influence of inhibitors and stimulators. Cathepsins D and E were the most active proteases studied and all enzymes were more active in leukocytes than in sediments from muscle tissue. The properties of these enzymes, compared with enzymes from other sources, and their possible involvement in meat tenderness are discussed. PMID- 22055055 TI - Effects of early-postmortem glycolytic rate on beef tenderness. AB - Electrical stimulation (ES) was applied at 500 V to one side from each of 60 beef carcasses at 30 to 40 min postmortem. Wide ranges of early-postmortem glycolytic and cooling rates were produced in the musculature by use of three different forms of ES (in addition to non-ES treatment of the contralateral sides) and application of chilling routines of four different degrees of severity. Panel and Warner-Bratzler shear evaluations of loin steaks from all 120 sides showed that tenderness was highest when glycolysis had proceeded at an intermediate rate (corresponding to the attainment of a 3-h pH of about 6.1) and was appreciably lower on both sides of this mid-value. The toughening effect of rapid glycolysis (relative to that of a moderately increased glycolytic rate) persisted through 14 days of aging at 2 degrees C. These observations appear to be incompatible with the view that lysosomal enzymes contribute significantly to ES-induced tenderization. They also indicate that the effect of ES on tenderness is highly dependent on the subsequent cooling rate, very slow chilling sometimes accelerating the already high rate of pH fall to such an extent that the tissue is significantly toughened. Finally, they suggest that the goal of maximizing the early-postmortem rate of pH decline in bovine muscle is misguided and, if attained, will cause sub-optimal tenderness. PMID- 22055056 TI - The effects of conditioning on meat collagen: Part 1-Evidence for gross in situ proteolysis. AB - The relative effectiveness of various reagents was investigated to determine the best method for extracting damaged collagen or collagen fragments from conditioned meat. SDS- and urea-washing were showd to yield clean connective tissue preparations and to extract the largest quantities of soluble collagen from perimysial preparations. Neutral 6m urea was used thereafter to extract soluble material from perimysial and endomysial preparations made from unconditioned and conditioned beef muscles. Eight bovine muscles of varying quality were examined. Conditioned muscles yielded significantly greater quantities of solubilized perimysial material than unconditioned muscles (P = 0.096) although the total collagen solubilized was very low (3.2-5.6% of total perimysial collagen). The amount of collagen or collagen fragments extracted from the eight perimysial preparations from conditioned muscles was significantly higher (P = 0.015) than from unconditioned muscles. Considerable variability in the percentage solubility of collagen from conditioned muscle perimysium was seen. This appeared to be site-specific. It was not possible to demonstrate similar changes in endomysial preparations due to the difficulty in quantitating the relatively low amounts of collagen in these fractions. PMID- 22055057 TI - Effect of ascorbic acid and alpha-tocopherol on storage stability of beef steaks. AB - Fresh beef loin steaks were dipped in solutions of (1) 70% ethyl alcohol (EtOH). (2) 70% EtOH containing 3% l-ascorbic acid (AsA), (3) 70% EtOH containing 0.08% dl-alpha-tocopherol (Toc) and (4) 70% EtOH containing 3% AsA plus 0.08% Toc for 20 s, then drained for 10 s. Control samples received no dip treatment. After 3, 6, 9 and 13 days of storage at 4 degrees C, the samples were evaluated for MetMb formation, TBA number and viable bacterial count. The beef steaks given AsA treatment maintained an acceptable meat colour for 13 days of storage. The TBA numbers of samples dipped in EtOH containing AsA stored for 13 days were significantly lower than those of controls, and in samples dipped in solutions without AsA. At 9 and 13 days of storage, the AsA plus Toc-treated samples gave lower TBA numbers than the samples given AsA treatment only. Viable bacterial counts were not affected by AsA, Toc or AsA plus Toc treatment. Beef loin steaks dipped in EtOH solution maintained a viable bacterial count of 10(6) after 13 days of storage. PMID- 22055058 TI - Tenderness of pork muscles as influenced by chilling rate and altered carcass suspension. AB - Tenderness improvements in porcine muscles (M. longissimus dorsi, LD; M. semimembranosus, SM; M. biceps femoris, BF) were evaluated in a total of 72 carcasses by using combinations of three different chilling rates (fast, delayed fast, slow) and two different suspension methods (Achilles tendon, pelvic bone). Tenderness was improved by fast chilling in LD, SM and BF by the pelvic suspension as compared to conventional suspension in the Achilles tendon (P < 0.05). The lengthening of the sarcomeres in SM and BF as produced by pelvic suspension exceeded those found in LD, without having proportional additional effect on the tenderness. While the pelvic-induced tenderization did not change significantly by delayed fast chilling, additional tenderization in BF and SM was obtained by combining pelvic suspension with slow chilling. In conventionally suspended sides, tenderness was unaffected by delayed fast chilling-with slow chilling, however, improvements were observed in LD and SM to a similar extent as obtained by the pelvic suspension. In the LD muscle, the tenderizing effect produced by treatments was largest in muscles having pH values 45 min post stunning above 6.1 (P < 0.05). PMID- 22055059 TI - Effect of feed energy intake on collagen characteristics and muscle quality of mature cows. AB - Samples from mature cows fed a high-energy and maintenance-energy diet for 84 days prior to slaughter were used to compare collagen solubility and palatability traits. Cows fed a high-energy diet prior to slaughter had increased percentage heat-labile collagen, less sensory panel detectable connective tissue and lower shear force values than cows fed a maintenance-energy diet. Mature cows fed a high-energy diet were fatter and had more marbling than cows fed a maintenance energy diet. The increased collagen solubility from feeding a high-energy diet to mature cows resulted in palatability and shear force ratings similar to those expected from young animals. PMID- 22055060 TI - Relation between muscular development and muscle collagen content in pigs. AB - The relationship between muscle collagen content and muscular development was investigated in the pig using eight Large Whites, eight halothane-negative (HN) and eight halothane-positive (HP) Pietrain pigs. Three muscles varying in the degree of hypertrophy in Pietrain pigs as compared to Large White pigs were studied. Pietrain pigs had higher loin and ham percentages, as well as higher muscle to bone ratio in the ham than Large White pigs. A trend to lower collagen contents in Pietrain pigs as compared to Large White pigs was observed in biceps femoris and longissimus dorsi muscles, although the differences were not significant. On the whole, there does not seem to be any clear relationship between muscle collagen content and muscular development in the porcine species. PMID- 22055061 TI - Effect of hot-boned pork on the keeping quality of fresh pork sausage. AB - The first experiment evaluated the effect of solid carbon dioxide (dry ice) addition to hot-boned meat, in different proportions, upon the keeping quality of fresh pork sausage patties. Dry ice had some negative effects at levels of 20% to 40%, such as hardening and colour fading of samples, although it increased water holding capacity of the sausage. In the second experiment three proportions of hot-boned meat and chilled meat were evaluated as a means to extend the retail storage time of fresh pork sausage links. Hot-boned pork was treated by three methods: freezing the meat before grinding, salting and freezing, and salting plus dry ice addition. The results favoured the use of 50% hot-boned meat and 50% chilled meat, for which the lowest hardness and oxidation values were obtained. Microbial counts and hue values showed no significant variation among the three treatments. Salting and freezing hot-boned meat before grinding was the method which produced the best overall quality. PMID- 22055063 TI - Influences of anatomical location and muscle quality on porcine lipid composition. AB - Carcasses of sixty Lacombe and Lacombe cross swine fed the same high concentrate ration were selected to equally represent three muscle quality groups (pale soft exudative (PSE), normal and dark firm dry (DFD)). These carcasses were utilised to supply back and belly fat samples for the evaluation of the influences of muscle quality and anatomical location on fatty acid composition. Back fat samples had lower percentages of palmitic (C16:0) and stearic (C18:0) acids, long (>= C18), and short (<= C16) chain saturated fatty acids and total saturated fatty acids and higher percentages of oleic (C18:1) and linoleic (C18:2) acids, polyunsaturated fatty acids and total unsaturated fatty acids than belly fat samples. They also had a higher unsaturated fatty acid to saturated fatty acid ratio than belly fat samples. Carcasses with DFD hams and loins had lower percentages of palmitoleic (C16:1) and linoleic (C18:2) acids and polyunsaturated fatty acids in their back fat than those with PSE hams and loins. They also had higher (P < 0.05) percentages of myristic (C14: 0) and stearic (C18:0) acids and long chain saturated fatty acids (>= C18) and lower percentages (P < 0.05) of palmitic (C16:0) and palmitoleic (C16:1) acids in their back fat than carcasses with normal hams and loins. Moreover, they had lower (P < 0.05) percentages of palmitoleic (C16:1) and linoleic (C18:2) acids and poly-unsaturated fatty acids in their belly fat than carcasses with normal and PSE hams and loins. The fact that the lipid composition of carcasses differed significantly among muscle quality groups is of considerable importance, since it implies that factors (stress) producing differences in muscle quality may also significantly influence the fatty acid composition-and thereby the physical properties of carcass lipids. PMID- 22055064 TI - Physiological basis of CO(2) inhibition of a meat spoilage bacterium, Pseudomonas fluorescens. AB - CO(2) has been shown to have a number of effects on biological systems, but it is uncertain which of these are important in its inhibition of Gram-negative spoilage bacteria. The effects of CO(2) on intracellular pH, in vitro enzyme actities and substrate transport were examined to see if any changes in these functions could be correlated with the observed patterns of growth inhibition, which varied with the composition of the growth medium. CO(2) inhibition of growth could not be explained by postulating inhibition of intracellular enzymes, but inhibition of substrate uptake appears to correlate with-and offer a satisfactory explanation for-growth inhibition. However, the data do not allow the inhibition of substrate transport to be ascribed to a particular mode of action of CO(2). PMID- 22055065 TI - Electroencephalographic studies of stunning and slaughter of sheep and calves- Part 3: The duration of insensibility induced by electrical stunning in sheep and calves. AB - The duration of insensibility produced by electrical and percussive stunning was studied in sheep and calves. Insensibility was determined from the study of electroencephalograms (EEG) and concurrent observations were made of the reflexes and reactions of the animals. The effect of stunning on the circulation was assessed from electrocardiograms (ECG) and femoral blood pressures (BP). Electrical stunning of sheep by electrodes to the head only produced a period of reversible insensibility of 18-42s. This technique also caused an immediate and prolonged increase in BP. Electrical stunning of both sheep and calves by a 'head to back' method, which causes concurrent cardiac dysfunction, produced immediate and permanent insensibility associated with cessation of circulation and an immediate drop in BP. The use of a non-penetrative method of percussion stunning caused immediate insensibility and an increase in BP which persisted after exsanguination had commenced. Calves stunned with a penetrating captive bolt showed immediate and permanent insensibility and the EEG became isoelectric within 15 s. PMID- 22055066 TI - The determination of haem pigments in meat. AB - The determination of haem pigment concentration in meat is described. The absorbancies of the extract are measured at 572, 565, 545 and 525 nm and the total concentrations, as well as the relative concentrations, of oxidized, oxygenated or reduced pigment forms are calculated. The procedure is simple and gives information in a single step which otherwise would be available only by using two separate methods. PMID- 22055067 TI - A plug sampling technique for measuring the pH of carcass muscles. AB - A modified surgical biopsy instrument has been developed for taking muscle samples from the M. longissimus dorsi of sheep carcasses. This instrument enables samples of approximately 2 g to be taken without mutilating the carcass. Samples from a range of carcasses were incubated in liquid paraffin for 24 h at approximately 20 degrees C and pH values measured after homogenisation in iodoacetate solution. The values obtained were an accurate measure of ultimate pH of the muscle at the site from which the plug samples were taken. This technique has a number of advantages over measurement by direct probe methods. PMID- 22055068 TI - Quality, palatability and weight loss of pork as affected by electrical stimulation. AB - Forty-five swine (n = 15, stress-susceptible pigs, fasted for 18 h; n = 15, normal pigs, fasted for 48, 60 or 72h; n = 15, normal pigs, fasted for 18 h) were slaughtered. One side of each pig was electrically stimulated (ES)-550 V, 2-6 A, seventeen impulses, 1.8 s on and 1.8 s off per impulse-and the opposite side was not stimulated (NS). Ham and loin temperatures were monitored at 12 and 24 hours post mortem. Carcass quality-marbling, loin eye colour, loin eye firmness, subcutaneous fat firmness and belly firmness-was evaluated at 24 hours post mortem. Sides were fabricated into four lean cuts at 48 hours; cuts were placed on open metal racks in a 2 degrees C cooler and weight loss was measured after 24, 48 and 72 hours storage. At 120 hours post mortem, loin chops were cut, frozen (-24 degrees C for 45 days) and subsequently used to determine thaw loss, cooking loss, Warner-Bratzler shear (WBS) force and palatability. Ham temperatures (12 h) were significantly (P < 0.05) lower for the ES sides from the stress-susceptible, short-fast (SSF) group but not for normal, long-fast (NLF) or normal, short-fast (NSF) groups. ES produced lighter coloured, softer loin eyes in the SSF group but darker coloured, firmer loin eyes and firmer subcutaneous fat in the NLF group. No significant differences (P > 0.05) were detected for thaw loss, cooking loss, palatability ratings or WBS values between ES and NS in the SSF group but chops from ES sides of NLF animals had significantly (P < 0.05) higher ratings for muscle fibre tenderness, overall tenderness and overall palatability. Weight losses of the lean cuts from the ES sides were higher (P < 0.05) than those from NS sides in only three of sixty comparisons of cuts from the three groups of swine. These data suggest that ES had very minimal effects on quality, palatability or weight loss of pork. PMID- 22055069 TI - Some aspects of the effectiveness of stunning in sheep by the captive bolt. AB - The effects of penetration depth and the velocity of the bolt on the onset of unconsciousness was investigated in twenty-four sheep of about 45 kg liveweight. The sheeps' state of consciousness was judged from the electrocorticograms recorded via electrodes surgically pre-implanted frontally on the right side of the head. Sixteen sheep were trephined. A commercial captive bolt pistol and an experimental manual bolt, both with variable penetration depths, were used to represent high and low velocity stunning. Stunning by destroying only the cortex or by only penetrating the skull when the experimental bolt or captive bolt pistol, respectively, were used, did not produce unconsciousness. Unconsciousness was obtained after destroying the cortex and deeper parts of the brain with the experimental bolt (low velocity) or after destroying the cortex (and deeper parts of the brain by shockwaves) when using a captive bolt pistol (high velocity). To produce unconsciousness the captive bolt should have sufficient energy and length after penetration of the skull to crush the cortex and deeper parts of the brain, either directly or by shockwaves. PMID- 22055070 TI - Aliphatic secondary amines in meat and fish products and their analysis by high pressure liquid chromatography. AB - A simple and reliable high pressure liquid chromatographic method for aliphatic secondary amines in foods has been developed. The method, which involves rapid extraction, derivatisation with dinitroflurobenzene and one-step liquid chromatographic analysis, allows dimethylamine to be determined without interference by the completing agent, whereas only a slight increase in the response of dimethylamine is caused by large amounts of trimethylamine. The presence of free secondary amines in a number of Italian meat and fish products and their formation as a consequence of some preservation techniques have been investigated. The results are discussed. PMID- 22055071 TI - Performance, carcass and palatability characteristics of Longhorn and other types of cattle. AB - Performance, carcass and palatability characteristics of Longhorn steers were compared with those of cattle currently popular in the United States-Hereford, Angus, Brahman, Holstein, two-breed crossbred (British beef breed crosses) and three-breed crossbred (1 4 dairy , 1 4 British beef and 1 2 European beef ) steers. Steers were fed roughage, then a growing diet (42 days), then a high energy (89% concentrate) diet (153 to 179 days by breed group) and slaughtered, individually, at USDA Choice finish or, failing that, after 186 days on the finishing diet. Data suggest that Longhorns, compared with types of cattle currently used: (1) are less desirable in physical appearance; (2) gain weight less rapidly, reaching the desired finish and slaughter weight as older animals; (3) convert feed to liveweight less efficiently; (4) deposit less subcutaneous fat, more internal fat, but essentially the same amount of intramuscular fat; (5) are as muscular (longissimus muscle area, estimated percentage of carcass muscle, muscle to bone ratio, muscle to fat ratio); (6) are as desirable in USDA quality grade and yield grade and (7) produce beef that is a palatable. PMID- 22055072 TI - Morphometric study of the layers of the canine small intestine at five sampling sites. AB - The histology of the canine intestine has not been accurately defined. To establish the precise thickness of its different layers, whole wall samples of the small intestine were removed from 41 cadavers at five standardised sampling sites (duodenum, proximal jejunum, distal jejunum, proximal ileum and distal ileum). The total thickness was estimated by morphometry, as was the thickness of the mucosa, muscularis mucosae, submucosa and muscularis externa. In addition, the size of the lymphoid aggregates in the submucosa and the thickness of the circular and longitudinal layers within both the muscularis mucosae and the muscularis externa were estimated. The total intestinal thickness depended very much upon the thickness of the mucosa and submucosa. The mucosa decreased progressively from proximal to distal parts of the small intestine (47% reduction). The thickness of the submucosa, however, changed little from the duodenum to the distal jejunum, but increased significantly in the ileum; this change was positively correlated with the amount of lymphoid tissue. Sex influenced the thickness of the intestinal wall, with males displaying higher thickness values along the small intestine. Conversely, no correlation between bodyweight and intestinal thickness was found for any of the five sampling sites. This study gives absolute and relative values for the thickness of the layers of the dog intestine which might help in the diagnosis of small intestinal pathology from postmortem samples and/or endoscopic biopsies. PMID- 22055074 TI - Assessment of a single-piece hydrophilic acrylic IOL for piggyback sulcus fixation in pseudophakic cadaver eyes. AB - PURPOSE: To evaluate a single-piece hydrophilic acrylic intraocular lens (IOL) designed for sulcus fixation in a piggyback configuration in postmortem pseudophakic human eyes. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Pseudophakic human cadaver eyes were imaged by high-frequency ultrasound (Artemis) to assess the overall position of the primary IOL and the sulcus diameter. The piggyback IOL (Sulcoflex) was then injected into the ciliary sulcus of these eyes. After fixation in formalin, they were reevaluated by high-frequency ultrasound for assessment of IOL fixation, fit, centration, tilt, and clearance from the primary IOL and intraocular structures and analyzed after sectioning. RESULTS: Data could be obtained from 11 eyes, all in which the primary IOL was located in the capsular bag. Different foldable IOLs and different degrees of Soemmerring ring formation were represented. The piggyback IOL could be injected and positioned in the ciliary sulcus and had overall appropriate centration and minimum or no tilt. Clearance between the 2 IOLs ranged from 232 to 779 MUm, mostly depending on the thickness of the primary IOL. Direct assessment of the sulcus-fixated haptics showed no disturbances to the ciliary processes. CONCLUSIONS: The new IOL has large optic and overall diameters, smooth and undulating haptics, and a convex concave optic profile. Results show that these characteristics minimize the possibility of interaction with the primary IOL and uveal tissues, decreasing the likelihood of optical aberrations and pigmentary dispersion. PMID- 22055073 TI - Association of biometric factors with anterior chamber angle widening and intraocular pressure reduction after uneventful phacoemulsification for cataract. AB - PURPOSE: To evaluate anterior chamber biometric factors associated with the degree of angle widening and intraocular pressure (IOP) reduction after phacoemulsification. SETTING: University of California, San Francisco, California, USA. DESIGN: Case series. METHODS: Anterior chamber parameters obtained by anterior segment coherence tomography were compared preoperatively and 3 months postoperatively. Measurements included the angle opening distance 500 MUm anterior to the scleral spur (AOD500), trabecular-iris space area 500 MUm from the scleral spur (TISA500), iris curvature (I-Curv), anterior chamber angle (ACA), trabecular-iris space area, anterior chamber volume, anterior chamber width, and lens vault (LV). RESULTS: The study enrolled 73 eyes. The mean patient age was 77.45 years +/- 7.84 (SD); 65.75% of patients were women. From preoperatively to 3 months postoperatively, the mean AOD500 increased significantly (0.254 +/- 0.105 to 0.433 +/- 0.108 mm) and the mean IOP decreased significantly (14.97 +/- 3.35 to 12.62 +/- 3.37 mm Hg) (P<.001). The reduction in IOP was correlated with the increase in AOD500 (r = 0.240, P=.041) and preoperative LV (r = 0.235, P=.045). After adjusting for related factors, AOD500 widening was positively correlated with LV (beta = 0.458, P=.044) and I-Curv (beta = 0.235, P=.043) and negatively correlated with preoperative TISA500 (beta = -0.269, P=.025) and ACA (beta = -0.919, P=.027). CONCLUSIONS: Surgically induced AOD widening was significantly correlated with anterior chamber biometric factors. Preoperative LV appears to be a significant factor in angle widening and IOP reduction after phacoemulsification. PMID- 22055075 TI - Changes in intraocular lens surface roughness during cataract surgery assessed by atomic force microscopy. AB - PURPOSE: To analyze the changes in optic surface roughness before and after injection of various intraocular lens (IOL) models using atomic force microscopy (AFM). SETTINGS: Departments of Ophthalmology, Medical University of Graz, General Hospital Linz and University Hospital Basel; Upper Austria University, School of Applied Health and Social Sciences, Linz, Austria. DESIGN: Experimental study. METHODS: The morphology and surface roughness of 3 hydrophobic acrylic IOLs from different manufacturers were analyzed by AFM in liquid using the tapping mode. First, AFM was performed on IOLs taken from the original package without further manipulation. In a second step, under sterile conditions, an experienced cataract surgeon loaded the IOLs into the appropriate injection system and pushed them through a system resembling an IOL implantation in cataract surgery; this was followed by AFM evaluation. Finally, 3 samples of a preloaded hydrophilic acrylic IOL taken from the original cartridge were compared with 3 samples that were pushed through the implantation system. RESULTS: Comparison of the arithmetic mean, standard deviation, root mean square, and surface skewness of the IOLs before and after injection showed a significant increase in surface roughness (P<.05). CONCLUSIONS: Standard application procedures of IOLs may alter the IOL surface. Increases in the surface roughness of IOLs may influence postoperative posterior capsule opacification. Further studies are necessary to evaluate the interfacial properties of IOLs. PMID- 22055076 TI - Intrastromal corneal ring segments for advanced keratoconus and cases with high keratometric asymmetry. AB - PURPOSE: To report the safety and efficacy of intrastromal corneal ring segment (ICRS) implantation to manage keratoconus. SETTING: Singleton Hospital Abertawe Bro Morgannwg University NHS Trust, Swansea, United Kingdom DESIGN: Case series. METHODS: Intacs SK ICRS were implanted manually for moderate to severe keratoconus and contact lens intolerance or ineffectiveness. Postoperative examinations were at 2 and 4 weeks; 3, 6, 9, and 12 months; and every 6 months thereafter. Outcome measures included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, corneal topography, and slitlamp examination. RESULTS: This study enrolled 31 eyes (29 patients; mean age 30 years). The mean UDVA was significantly better 12 months postoperatively (0.88 logMAR) than preoperatively (1.40 logMAR) (P=.001), as was the mean CDVA (0.29 logMAR versus 0.44 logMAR) (P=.04). The mean spherical equivalent was -6.57 diopters (D) preoperatively and -2.84 D at 12 months (P=.01). The mean keratometry (K) reading decreased from 52.07 D (range 45.9 to 63.1 D) to 46.15 D (range 39.2 to 52.9 D) for K1 (P<.0001) and from 57.9 D (range 52.5 to 69.7 D) to 51.2 D (range 46.8 to 58.3 D) for K2 (P<.0001). There were no intraoperative complications; however, 6 patients had segment extrusion. CONCLUSION: Implantation of ICRS was useful in managing keratoconus, producing up to 12.00 D of corneal flattening, which improved CDVA and allowed contact lens tolerance in all cases. PMID- 22055081 TI - The colour and colour stability of beef Longissimus dorsi and Semimembranosus muscles after effective electrical stimulation. AB - The influence of effective low voltage electrical stimulation (ES) of beef on the colour and colour stability of longissimus dorsi (LD) and semimembranosus (SM) muscles, during storage and retail display was studied by tristimulus colorimetry and reflectance spectrophotometry. ES had no significant effect on the colour of the LD muscles, but some significant effects on SM muscles of ultimate pH 5.5 5.7. Three hours after slicing into steaks at 5 days post mortem, stimulated SM muscles had a paler/lighter colour than non-stimulated controls. During a retail display of 3 days, all steaks exhibited a loss of colour quality manifested in loss of redness and decreases in both hue and chroma (saturation). These changes were most marked in the stimulated SM muscles, and analysis indicated that they were due almost exclusively to the formation of metmyoglobin (metMb). Ageing the meat, as primals cuts, for 33 days at 0 degrees C led to no significant differences in the perceived colour three hours after slicing. The colour changes observed during the 3-day retail display of steaks occurred more rapidly in both (ES and non-ES) 33 day-aged samples than in the 5 day-aged ones. The result of this was that the colour stability of non-stimulated steaks prepared at 33 days was similar to that of ES steaks prepared fresh (5 day post mortem). In SM muscles of pH 5.8-6.0 the apparent differences in colour of the ES and non-ES samples were not significant. However, meat of pH > 5.8, although darker than meat of lesser pH, had less tendency to form metmyoglobin during retail display. The present work also confirmed that seemingly small differences in display conditions, especially temperature, have a marked effect on metmyoglobin formation. PMID- 22055077 TI - Rotational stability of a toric intraocular lens: influence of axial length and alignment in the capsular bag. AB - PURPOSE: To evaluate the rotational stability of a toric intraocular lens (IOL) using purpose-designed software and to determine the influence of axial length (AL) and in-the-bag IOL alignment on IOL rotation. SETTING: Iladevi Cataract & IOL Research Centre, Ahmedabad, India. DESIGN: Prospective observational case series. METHODS: This study enrolled eyes that had AcrySof toric IOL implantation. The AL was measured using optical coherence biometry or immersion A scan biometry. Corneal astigmatism was determined by manual keratometry and topography. The IOL alignment was vertical, horizontal, or oblique. Rotational stability was measured using the purpose-designed software, and the mean absolute difference was determined. The effect of AL and IOL alignment on rotational stability was determined 6 months postoperatively. RESULTS: The study evaluated 168 eyes (168 patients). The mean AL was 23.86 mm +/- 1.63 (SD), (range 19.50 to 29.03 mm). The median IOL rotation was 0.3 degree from baseline to 1 week, 1.0 degree from 1 week to 1 month, 0.2 degree from 1 to 3 months, and 0.1 degree from 3 to 6 months. The maximum rotation occurred between 1 week and 1 month. There was a strong correlation between AL and IOL rotation at 6 months (r = 0.93, P<.001). The mean absolute difference at 6 months was not significantly different between the 3 axis placement categories when correlated with the rotation (P=.102, analysis of variance). CONCLUSIONS: Toric IOL rotation was greater in eyes with a longer AL. Alignment of the IOL in the capsular bag had no influence on rotation. PMID- 22055082 TI - Sarcomere shortening of prerigor muscles and its influence on drip loss. AB - Detailed studies of muscle shortening post mortem at incubation temperatures between -2 degrees C and +38 degrees C revealed that the sarcomeres in unrestrained, excised red bovine muscle (M. sternomandibularis) shortened less than 10 % in the prerigor state between 6 degrees C and 18 degrees C. Below 6 degrees C, sarcomeres contracted up to 70%. Between 20 degrees C and 38 degrees C sarcomere shortening of 40% was observed. In the red porcine M. cleidooccipitalis the minimum of shortening was measured at about 10 degrees C, a higher degree of shortening-up to 50%-being obtained above and below this temperature. The drip loss of both muscle types increased linearly with increasing prerigor shortening. This latter relationship is discussed with regard to changes within the muscle post mortem. The influence of three events on water movement from the interfilamental space into the interfibrillar fluid and from there into the extracellular space is critically evaluated. These events are: (1) the prerigor contraction of sarcomeres depending on the temperature of storage, (2) the changes due to the falling pH post mortem and (3) the onset of rigor mortis, with its irreversible association of actin and myosin. PMID- 22055083 TI - A comparison of distribution and composition of intramuscular fat in Duroc Jersey and Hampshire pigs at 100 kg liveweight. AB - The intramuscular fat content, its fatty acid composition and that from the triglyceride fraction, were determined in several muscles from the right sides of four Duroc Jersey and four Hampshire castrated male pigs slaughtered at 100 kg liveweight. The Hampshires had heavier muscles than the Duroc Jersey pigs, but did not show significant differences in the percentages of intramuscular fat. The concentrations of linoleic acid were, in general, higher in the Hampshire than in the Duroc Jersey pigs and in many muscles the differences were highly significant (p < 0.05) The concentrations of linoleic acid (18:2) in the triglyceride fraction did not differ among muscles within breeds but were higher in Hampshire than in Duroc Jersey pigs. PMID- 22055084 TI - Conformational changes in the muscle proteins of cured beef during heating. AB - Structural changes caused by heating in the proteins of cured beef longissimus dorsi muscle were examined by fluorescence and differential scanning calorimetry. Denaturation occurred in four temperature ranges-40-55 degrees C, 55-61 degrees C, 62-70 degrees C and above 70 degrees C, in contrast to the three endothermic transitions reported for non-cured meats. PMID- 22055085 TI - Compositional and enzymatic characteristics of the Longissimus Dorsi muscle from large white, halothane-positive and halothane-negative pietrain, and hampshire pigs. AB - One-hundred-and-twenty-nine pigs from four genetic types-Large Whites, halothane negative (HN) and halothane-positive (HP) Pietrains and Hampshires-were used to study some compositional and enzymatic muscle traits. Water, nitrogen, hydroxyproline and lipid contents, as well as lactate dehydrogenase and citrate synthase activities, were measured on all pigs, whereas glycogen phosphorylases (a and a + b), glycogen synthetase I + D and myosin isozyme pattern were determined on only fifty-six pigs. Hampshires were markedly different from the other genetic types with respect to the characteristics studied. Their Longissimus dorsi muscle contained less nitrogen (P < 0.0) and more lipid (P < 0.01) and presented higher hydroxyproline to nitrogen (P < 0.001) and water to nitrogen (P < 0.001) ratios, as well as noticeably higher citrate synthase (P < 0.01) and glycogen synthetase. PMID- 22055086 TI - Electrical stimulation of post-mortem glycolysis in the Semitendinosus muscle of sheep. AB - Changes in pH and phosphorylase a content in control and electrically stimulated Semitendinosus muscles of sheep were studied. The results provided evidence of acceleration of glycolysis during slaughter and sampling. In muscle electrically stimulated soon after slaughter there was a transient increase in phosphorylase a during stimulation. The magnitude of this increase and of the fall in pH during stimulation both depended on the pH of the muscle at the time of stimulation and reduced to zero when this pH was about 6.3. There was little or no phosphorylase a in samples of muscle taken about 35 min post mortem or, at any time, in muscle electrically stimulated about 35 min post mortem. Possible reasons for the transient nature of the increase in phosphorylase a content during stimulation are discussed. PMID- 22055087 TI - Effect of chemical dips on unchilled fresh beef inoculated with E. coli, S. aureus, S. faecalis and Cl. perfringens and Stored at 30 degrees C and 20 degrees C. AB - The antimicrobial effect of three chemical dips (A: potassium sorbate, 20g; sodium acetate, 5g; sodium chloride, 5g; water, 100 ml. B: potassium sorbate, 20g; sodium acetate, 5g; sodium chloride, 5g; propylene glycol, 20 ml; glycerol, 10 ml; water, 70 ml and 0.5N NaOH to pH 10. C: potassium sorbate, 10 g; sodium acetate, 10 g; sodium citrate, 10g; sodium chloride, 5g; water, 100 ml and 0.5N NaOH to pH 10) on unchilled f resh beef samples inoculated with E. coli, S. aureus, S. faecalis and Cl. perfringens and stored at 30 degrees C and 20 degrees C was investigated. Treatments had produced a significant (P < 0.01) inhibitory effect on all the organisms inoculated, with a reduction of about 3 to 5 log units compared with the control. pH changes were comparable with the control at 5 degrees C. No significant differences were found between the treatments and shelf life could be extended up to 44 h at 30 degrees C and 68 h at 20 degrees C whilst, in the control, visual spoilage and high bacterial counts were observed by 20h at 30 degrees C and by 20 to 32h at 20 degrees C. Treatment C, containing potassium sorbate at a low level (10%), was considered better than treatments A and B since potassium sorbate at higher levels had produced slight off-odours without a greater inhibitory effect. PMID- 22055088 TI - The detection and partial characterization of horse muscle soluble proteins by imnmnoelectrophoresis in agarose gels. AB - Immunoele ctrophoresis in agarose gels has been used to detect and partially characterize specific protein precipitin hands of horse muscle soluble proteins (HSP), free of cross reactions with the muscle soluble proteins of cow (CSP) and pig (PSP). Of seven precpptin bands obtained by reacting HSP against an anti-HSP antiserum produced by a rabbit, only one was observed to appear by reacting PSP against the same anti-HSP antiserum. This band, and two more, were detected when CSP were analyzed against an anti-HSP antiserum. The other four bands were specific f or the horse muscle soluble proteins. This technique may have the potential to detect the presence of horse meat in unheated ground meat products. PMID- 22055089 TI - The physical basis of meat texture: Observations on the fracture behaviour of cooked bovine M. Semitendinosus. AB - The fracture behaviour of cooked strips of beef M. semitendinosus was studied by qualitative observation of the manner in which fracture occurred and by quantitative measurements of ultimate tensile strength, work of fracture and notch sensitivity. Qualitative observations showed that fracture started in the perimysial connective tissue in all test configurations used, resulting initially in the separation of intact muscle fibre bundles. The ultimate tensile strength along and across the fibres was ~-300kNm(-2) and ~-25kNm(-2), respectively. The qualitative aspects of fracture were explained on the basis of a uniaxial fibrous composite of strong muscle fibre bundles in a weak connective tissue 'matrix', with poor interfacial strength. Work of fracture through the perimysium was in the range 0.4 to 1.8kJm(-2). The difficulty in propagating fracture across the muscle fibre bundles was explained in terms of the material's complete insensitivity to notches running across the fibres. The results imply that the muscle fibre bundle is an important level of structural organisation as far as fracture is concerned and that the strength of the perimysium, or perimysium/muscle fibre bundle interface, is likely to have a major influence on the toughness of'the cooked meat. PMID- 22055090 TI - Influence of aerobic and anoxic microenvironments on polyhydroxyalkanoates (PHA) production from food waste and acidogenic effluents using aerobic consortia. AB - The functional role of aerobic and anoxic microenvironments on polyhydroxyalkanoates (PHA) production using food waste (UFW) and effluents from acidogenic biohydrogen production process (FFW) were studied employing aerobic mixed culture as biocatalyst. Anoxic microenvironment documented higher PHA production, while aerobic microenvironment showed higher substrate degradation. FFW showed higher PHA accumulation (39.6%) than UFW (35.6%) due to ready availability of precursors (fatty acids). Higher fraction of poly-3-hydroxy butyrate (PHB) was observed compared to poly-3-hydroxy valerate (PHV) in the accumulated PHA in the form of co-polymer [P3(HB-co-HV)]. Dehydrogenase, phosphatase and protease enzymatic activities were monitored during process operation. Integration with fermentative biohydrogen production yielded additional substrate degradation under both aerobic (78%) and anoxic (72%) microenvironments apart from PHA production. Microbial community analysis documented the presence of aerobic and facultative organisms capable of producing PHA. Integration strategy showed feasibility of producing hydrogen along with PHA by consuming fatty acids generated during acidogenic process in association with increased treatment efficiency. PMID- 22055091 TI - Torrefaction of sawdust in a fluidized bed reactor. AB - In the present work, stable fluidization of sawdust was achieved in a bench fluidized bed with an inclined orifice distributor without inert bed materials. A solids circulation pattern was established in the bed without the presence of slugging and channeling. The effects of treatment severity and weight loss on the solid product properties were identified. The decomposition of hemicelluloses was found to be responsible for the significant changes of chemical, physical and mechanical properties of the torrefied sawdust, including energy content, particle size distribution and moisture absorption capacity. The hydrophobicity of the torrefied sawdust was improved over the raw sawdust with a reduction of around 40 wt.% in saturated water uptake rate, and enhanced with increasing the treatment severity due to the decomposition of hemicelluloses which are rich in hydroxyl groups. The results in this study provided the basis for torrefaction in fluidized bed reactors. PMID- 22055092 TI - Simultaneous production of 3-hydroxypropionic acid and 1,3-propanediol from glycerol by a recombinant strain of Klebsiella pneumoniae. AB - In this study, an aldehyde dehydrogenase (ALDH) was over-expressed in Klebsiella pneumoniae for simultaneous production of 3-hydroxypropionic acid (3-HP) and 1,3 propanediol (1,3-PDO). Various genes encoding ALDH were cloned and expressed in K. pneumoniae, and expression of Escherichia colialdH resulted in the highest 3 HP titer in anaerobic cultures in shake flasks. Anaerobic fed-batch culture of this recombinant strain was further performed in a 5-L reactor. The 3-HP concentration and yield reached 24.4 g/L and 0.18 mol/mol glycerol, respectively, and at the same time 1,3-PDO achieved 49.3 g/L with a yield of 0.43 mol/mol in 24 h. The overall yield of 3-HP plus 1,3-PDO was 0.61 mol/mol. Over-expression of the E. coli AldH also reduced the yields of by-products except for lactate. This study demonstrated the possibility of simultaneous production of 3-HP and 1,3-PDO by K. pneumoniae under anaerobic conditions without supply of vitamin B12. PMID- 22055093 TI - Biosorption and desorption of Nickel on oil cake: batch and column studies. AB - Biosorption potential of mustard oil cake (MOC) for Ni(II) from aqueous medium was studied. Spectroscopic studies showed possible involvement of acidic (hydroxyl, carbonyl and carboxyl) groups in biosorption. Optimum biosorption was observed at pH 8. Contact time, reaction temperature, biosorbent dose and adsorbate concentration showed significant influence. Linear and non-linear isotherms comparison suggests applicability of Temkin model at 303 and 313 K and Freundlich model at 323K. Kinetics studies revealed applicability of Pseudo second-order model. The process was endothermic and spontaneous. Freundlich constant (n) and activation energy (Ea) values confirm physical nature of the process. The breakthrough and exhaustive capacities for 5 mg/L initial Ni(II) concentration were 0.25 and 4.5 mg/g, while for 10 mg/L initial Ni(II) concentration were 4.5 and 9.5 mg/g, respectively. Batch desorption studies showed maximum Ni(II) recovery in acidic medium. Regeneration studies by batch and column process confirmed reutilization of biomass without appreciable loss in biosorption. PMID- 22055094 TI - Iterative linear integral isoconversional method: theory and application. AB - In this work, the theory of the iterative linear integral isoconversional method was illustrated in detail. This method allows the dependence of the activation energy (Ealpha) on the conversion degree to be accurately determined in a short time. Moreover, the method can yield the term [Aalphaf(alpha)] (Aalpha: the frequency factor at conversion alpha, f(alpha): the reaction model). The obtained Ealpha and [Aalphaf(alpha)] values can be used to reconstruct the kinetic conversion data at experimental and extrapolated conditions. The suggested method was applied to the experimental data of combustion of biomass fast pyrolysis char, and the corresponding kinetic parameters were obtained. PMID- 22055095 TI - Closing the carbon balance for fermentation by Clostridium thermocellum (ATCC 27405). AB - Our lab and most others have not been able to close a carbon balance for fermentation by the thermophilic, cellulolytic anaerobe, Clostridium thermocellum. We undertook a detailed accounting of product formation in C. thermocellum ATCC 27405. Elemental analysis revealed that for both cellulose (Avicel) and cellobiose, >=92% of the substrate carbon utilized could be accounted for in the pellet, supernatant and off-gas when including sampling. However, 11.1% of the original substrate carbon was found in the liquid phase and not in the form of commonly-measured fermentation products--ethanol, acetate, lactate, and formate. Further detailed analysis revealed all the products to be <720 da and have not usually been associated with C. thermocellum fermentation, including malate, pyruvate, uracil, soluble glucans, and extracellular free amino acids. By accounting for these products, 92.9% and 93.2% of the final product carbon was identified during growth on cellobiose and Avicel, respectively. PMID- 22055096 TI - Performance of a submerged membrane bioreactor for the aerobic treatment of abattoir wastewater. AB - The performance of a submerged membrane bioreactor (SMBR) has been investigated for abattoir wastewater (AW) treatment. The chemical oxygen demand (COD) of permeate has not exceeded 25 mg L(-1) providing an average COD removal of 98%. Microbiological analysis showed that the SMBR has allowed a complete removal of fecal coliforms, Listeria and Salmonella. A significant reduction in the excess biomass production was also observed. In fact, the yield of biomass production (Yobs) ranged between 0 and 0.106 g suspended solids/g COD removed. The study of the dynamic of bacterial communities using the single strand conformation polymorphism (SSCP) method showed a significant change in the population structure and revealed a correlation between the sludge production yield and the bacterial communities. PMID- 22055097 TI - Learning from pairwise constraints by Similarity Neural Networks. AB - In this paper we present Similarity Neural Networks (SNNs), a neural network model able to learn a similarity measure for pairs of patterns, exploiting a binary supervision on their similarity/dissimilarity relationships. Pairwise relationships, also referred to as pairwise constraints, generally contain less information than class labels, but, in some contexts, are easier to obtain from human supervisors. The SNN architecture guarantees the basic properties of a similarity measure (symmetry and non negativity) and it can deal with non transitivity of the similarity criterion. Unlike the majority of the metric learning algorithms proposed so far, it can model non-linear relationships among data still providing a natural out-of-sample extension to novel pairs of patterns. The theoretical properties of SNNs and their application to Semi Supervised Clustering are investigated. In particular, we introduce a novel technique that allows the clustering algorithm to compute the optimal representatives of a data partition by means of backpropagation on the input layer, biased by a L(2) norm regularizer. An extensive set of experimental results are provided to compare SNNs with the most popular similarity learning algorithms. Both on benchmarks and real world data, SNNs and SNN-based clustering show improved performances, assessing the advantage of the proposed neural network approach to similarity measure learning. PMID- 22055098 TI - Long-term effects of inhaled treprostinil in patients with pulmonary arterial hypertension: the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study open-label extension. AB - BACKGROUND: Inhaled treprostinil improved functional capacity as add-on therapy in the short-term management of patients with pulmonary arterial hypertension (PAH). This study investigated the long-term effects of inhaled treprostinil in patients concurrently receiving oral background therapy. METHODS: A total of 206 patients (81% women) completing the 12-week double-blind phase of the Treprostinil Sodium Inhalation Used in the Management of Pulmonary Arterial Hypertension (TRIUMPH) study transitioned into an open-label extension. Patients were assessed every 3 months for changes in 6-minute walk distance (6MWD), Borg dyspnea score, New York Heart Association (NYHA) functional class, quality of life (QOL) scores, and signs and symptoms of PAH. RESULTS: Patients were primarily NYHA class III (86%), with a mean baseline 6MWD of 349 +/- 81 meters. A median change in 6MWD of 28, 31, 32, and 18 meters in patients continuing therapy was observed at 6, 12, 18, and 24 months, respectively. This effect was more prominent in those patients originally allocated to active therapy in the double blind phase. Survival rates for patients remaining on therapy were 97%, 94%, and 91% at 12, 18, and 24 months, respectively. In addition, 82%, 74%, and 69% of patients maintained treatment benefit as evidenced by lack of clinical worsening at 12, 18, and 24 months. The most common adverse events were known effects of prostanoid therapy (headache [34%], nausea [21%], and vomiting [10%]) or were due to the route of administration (cough [53%], pharyngolaryngeal pain [13%], and chest pain [13%]). CONCLUSIONS: Long-term therapy with inhaled treprostinil demonstrated persistent benefit for PAH patients who remained on therapy for up to 24 months. PMID- 22055099 TI - Interleukin-16 deficiency suppresses the development of chronic rejection in murine cardiac transplantation model. AB - BACKGROUND: IL-16 promotes the recruitment of various cells expressing CD4, a receptor for IL-16. The precise role of IL-16 in transplant rejection remains unknown; therefore, the present study investigated the contribution of IL-16 to the development of chronic rejection in heart transplants. METHODS: C-H 2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into (1) IL-16-deficient (IL-16(-/-)) C57BL/6J or (b) wild type (WT) control recipients (MHC class II mismatch). Grafts were harvested at 52 days, parenchymal rejection was assessed by the ISHLT grading system, and CAV was examined morphometrically. Graft infiltrating cells were detected 10 and 52 days after transplantation. Intragraft cytokine and chemokine profiles were assessed. To confirm the role of IL-16 in CAV development, C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into C57BL/6J WT recipients treated with (1) anti-IL-16-neutralization monoclonal antibody or (b) control immunoglobulin G. Grafts were harvested at 52 days, and CAV was quantified morphometrically. Graft-infiltrating cells were examined histologically. RESULTS: Parenchymal rejection and CAV was significantly attenuated in donor hearts transplanted into IL-16(-/-) recipient mice compared with WT controls. Donor hearts transplanted into IL-16(-/-) recipients had a significant reduction in coronary artery luminal occlusion, intima-to-media ratio, and percentage of diseased vessels. CAV was associated with decreased donor organ inflammation, as well as donor organ cytokine (IL-1beta and IL-6) and chemokine (MCP-1 and KC) protein expression. Intimal proliferation and inflammatory cell infiltration were significantly reduced in hearts transplanted into recipients treated with an IL-16-neutralization antibody. CONCLUSIONS: IL-16 deficiency reduced graft inflammatory cell recruitment, and allograft inflammatory cytokine and chemokine production. Therefore, IL-16 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection. PMID- 22055100 TI - An in vitro nutritive evaluation of olive tree (Olea europaea) pruning residues as affected by cutting regimen. AB - Nutritive values of the branches from Olea europaea trees cut at 25, 50, 75 or 100 cm distance from the tip were evaluated by determination of the in vitro digestible organic matter (IVDOM), metabolizable energy (ME), net energy lactation (NEL), and presence nutritional and anti-nutritional components. The values of nutritive components, nitrogen forms, IVDOM, ME and NEL declined and concentrations of crude fiber and cell wall constituents increased with the increase in cutting length. Total phenols, hydrolysable tannins and condensed tannins amounted to 70, 17 and 0.6 g/kg DM, respectively. The addition of polyethylene glycol (PEG, 6000) to the plant samples incubated with rumen fluid at a ratio of (2:1 PEG:substrate) increased the values of IVDOM, ME and NEL by 40 g/kg DM, 0.59 MJ/kg DM and 0.42 MJ/kg DM, respectively. IVDOM, ME and NEL were negatively correlated with crude fiber and cell wall constituents but positively correlated with nitrogen forms and non-fiber carbohydrates. Olive pruning branches in diameter<3 mm could be used as sources of feeds for small ruminants. PMID- 22055101 TI - NIRS-aided monitoring and prediction of biogas yields from maize silage at a full scale biogas plant applying lumped kinetics. AB - The aim of this study was to apply near-infrared spectroscopy (NIRS), available biogas plant data and lumped degradation kinetics to predict biogas production (BPr) of maize silage. A full-scale agricultural biogas plant was equipped with NIRS-metrology at the feeding station. Continuously NIR-spectra were collected for 520 d. Substrate samples were analyzed by means of feedstuff analysis. Biogas potential of the samples was calculated from the laboratory analysis results and for a sample-subset practically assessed by "Hohenheim biogas tests". NIRS regression-models for all mentioned parameters were calibrated. Continuously gathered spectra, NIRS-models, actual plant-feeding data and degradation kinetics were used to calculate time-series of theoretically expectable BPr. Results were validated against measured gas quantity. Determination coefficients between calculated and measured BPr were up to 58.2%. This outcome was mainly due to the positive correlation between BPr and input amount since the substrate was very homogeneous. The use of NIRS seems more promising for plants with stronger substrate heterogeneity. PMID- 22055102 TI - Ethanol production by continuous fermentation of D-(+)-cellobiose, D-(+)-xylose and sugarcane bagasse hydrolysate using the thermoanaerobe Caloramator boliviensis. AB - The recently isolated anaerobic bacterium Caloramator boliviensis with an optimum growth temperature of 60 degrees C can efficiently convert hexoses and pentoses into ethanol. When fermentations of pure sugars and a pentose-rich sugarcane bagasse hydrolysate were carried out in a packed bed reactor with immobilized cells of C. boliviensis, more than 98% of substrates were converted. Ethanol yields of 0.40-0.46 g/g of sugar were obtained when sugarcane bagasse hydrolysate was fermented. These features reveal interesting properties of C. boliviensis in producing ethanol from a renewable feedstock. PMID- 22055103 TI - Equilibrium and kinetics studies of heavy metal ions biosorption on green algae waste biomass. AB - The biosorption of Pb(II), Cd(II), and Co(II), respectively, from aqueous solution on green algae waste biomass was investigated. The green algae waste biomass was obtained from marine green algae after extraction of oil, and was used as low-cost biosorbent. Batch shaking experiments were performed to examine the effects of initial solution pH, contact time and temperature. The equilibrium biosorption data were analyzed using two isotherm models (Langmuir and Freundlich) and two kinetics models (pseudo-first order and pseudo-second order). The results indicate that Langmuir model provide best correlation of experimental data, and the pseudo-second order kinetic equation could best describe the biosorption kinetics of considered heavy metals. PMID- 22055104 TI - Treatment of poultry slaughterhouse wastewater in hybrid upflow anaerobic sludge blanket reactor packed with pleated poly vinyl chloride rings. AB - In this study, the performance of 5.4 L hybrid upflow anaerobic sludge blanket (HUASB) reactor for treating poultry slaughterhouse wastewater under mesophilic conditions (29-35 degrees C), was investigated. After starting-up, the reactor was loaded up to an OLR of 19 kg COD/m3 d and achieved varied TCOD and SCOD removal efficiencies of 70-86% and 80-92%, respectively. The biogas was varied between 1.1 and 5.2 m3/m3 d with the maximum methane content of 72%. The maximum methane yield was 0.32 m3/kg CODremoved at an OLR of 9.27 kg COD/m3 d. Black matured granules of size between 2.5 and 5 mm were observed at the end of 225 d operation. RTD study showed the flow behavior was in mixed regime at the end of performance study. Step wise polynomial regression analysis was fitted well. Methanobacterium and Methanosaeta bacteria were dominant at the end of start-up whereas Methanosarcina, Cocci and rods were predominant at the end of performance studies. PMID- 22055105 TI - Estimating biofilm reaction kinetics using hybrid mechanistic-neural network rate function model. AB - This work describes an alternative method for estimation of reaction rate of a biofilm process without using a model equation. A first principles model of the biofilm process is integrated with artificial neural networks to derive a hybrid mechanistic-neural network rate function model (HMNNRFM), and this combined model structure is used to estimate the complex kinetics of the biofilm process as a consequence of the validation of its steady state solution. The performance of the proposed methodology is studied with the aid of the experimental data of an anaerobic fixed bed biofilm reactor. The statistical significance of the method is also analyzed by means of the coefficient of determination (R2) and model efficiency (ME). The results demonstrate the effectiveness of HMNNRFM for estimating the complex kinetics of the biofilm process involved in the treatment of industry wastewater. PMID- 22055106 TI - Pyrolytic characteristics of biomass acid hydrolysis residue rich in lignin. AB - Pyrolytic characteristics of acid hydrolysis residue (AHR) of corncob and pinewood (CAHR, WAHR) were investigated using a thermo-gravimetric analyzer (TGA) and a self-designed pyrolysis apparatus. Gasification reactivity of CAHR char was then examined using TGA and X-ray diffractometer. Result of TGA showed that thermal degradation curves of AHR descended smoothly along with temperature increasing from 150 degrees C to 850 degrees C, while a "sharp mass loss stage" for original biomass feedstock (OBF) was observed. Char yield from AHR (42.64 30.35 wt.%) was found to be much greater than that from OBF (26.4-19.15 wt.%). In addition, gasification reactivity of CAHR char was lower than that of corncob char, and there was big difference in micro-crystallite structure. It was also found that CAHR char reactivity decreased with pyrolysis temperature, but increased with pyrolysis heating rate and gasification temperature at 850-950 degrees C. Furthermore, CAHR char reactivity performed better under steam atmosphere than under CO2 atmosphere. PMID- 22055107 TI - Characterization and further stabilization of a new anti-prelog specific alcohol dehydrogenase from Thermus thermophilus HB27 for asymmetric reduction of carbonyl compounds. AB - The use of dehydrogenases in asymmetric chemistry has exponentially grown in the last decades facilitated by the genome mining. Here, a new short-chain alcohol dehydrogenase from Thermus thermophilus HB27 has been expressed, purified, characterized and stabilized by immobilization on solid supports. The enzyme catalyzes both oxidative and reductive reactions at neutral pH with a broad range of substrates. Its highest activity was found towards the reduction of 2,2',2" trifluoroacetophenone (85 U/mg at 65 degrees C and pH 7). Moreover, the enzyme was stabilized more than 200-fold by multipoint covalent immobilization on agarose matrixes via glyoxyl chemistry. Such heterogeneous catalyst coupled to an immobilized cofactor recycling partner performed the quantitative asymmetric reduction of 2,2',2"-trifluoroacetophenone and rac-2-phenylpropanal to (S)-(+) alpha-(trifluoromethyl)benzyl alcohol and (R)-2-phenyl-1-propanol with enantiomeric excesses of 96% and 71%, respectively. To our knowledge this is the first alcohol dehydrogenase from a thermophilic source with anti-Prelog selectivity for aryl ketones and that preferentially produces R-profens. PMID- 22055108 TI - Depression in pregnancy is associated with preexisting but not pregnancy-induced hypertension. AB - BACKGROUND: The aim was to examine whether depression is associated with preexisting hypertension or pregnancy-induced hypertension in a large sample of women attending a university-based obstetrics clinic. METHODS: In this prospective study, participants were 2398 women receiving ongoing prenatal care at a university-based obstetrics clinic from January 2004 through January 2009. Prevalence of depression was measured using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria based on the Patient Health Questionnaire-9 as well as the self-reported use of antidepressant medication. Evidence of preexisting hypertension, pregnancy-induced hypertension and preeclampsia/eclampsia was determined by obstetrician International Classification of Diseases, Ninth Revision codes. Logistic regression was used to quantify the association between hypertension in pregnancy and antenatal depression. RESULTS: After adjusting for sociodemographic variables, chronic medical conditions, smoking and prior pregnancy complications, women with preexisting hypertension had an increased risk of any depression (minor, major, use of antidepressants) [odds ratio (OR)=1.55, 95% confidence interval (CI) 1.08 2.23) and major depression and/or use of antidepressants (OR=1.65, 95% CI 1.10 2.48) compared to women without hypertension. No differences were seen in risk of depression in women with pregnancy-induced hypertension or preeclampsia/eclampsia compared to those without hypertension. CONCLUSION: Women with preexisting hypertension, but not pregnancy-induced hypertension, are more likely to meet criteria for an antenatal depressive disorder and/or to be treated with antidepressants and could be targeted by obstetricians for screening for depression and enhanced treatment. PMID- 22055109 TI - The changes of potassium currents in RCS rat Muller cell during retinal degeneration. AB - Muller cells are the principal glial cells expressing membrane-bound potassium channel and predominantly mediating the homeostatic regulation of extracellular K+ produced by neuronal activity in retina. It's well known that Muller cells can be activated in many pathological conditions, but little is known about the change of potassium currents of Muller cells during the progression of retinitis pigmentosa. Herein, the Royal College of Surgeons rats (RCS rat) were employed to investigate some phenotypic and functional changes of Muller cells during retinal degeneration such as the expression of Kir4.1, membrane properties and K+ channel currents by using immunohistochemistry, RT-PCR, western blot and whole-cell patch clamping respectively. Compared with Muller cells in control retina, increased glutamine synthetase (GS) mRNA levels were seen at P30 and P60, and then decreased gradually in RCS rat retina. Morphologically, Muller cells showed significant hypertrophy and proliferation after p60. The increased expression of intermediate filament, glial fibrillary acidic protein (GFAP) and vimentin began at P30 and reached a peak at p60. Kir4.1 channels presented a peak expression at P30. Concomitantly, K(+) currents of Muller cells increased at P30 and decreased at P90 significantly. We concluded that retinal Muller cells of RCS rats underwent an activation initiated by the onset of retinal degeneration before p60 and then an obvious reactive gliosis, which led the basic membrane properties to suffer marked changes, and caused the Kir4.1 channels of Muller cells to occur a clear functional shift, even lose their normal electrophysiological properties. This process aggravates the impairment caused by the initial photoreceptor degeneration. PMID- 22055110 TI - Lymphatic drainage in prostate carcinoma assessed by lymphoscintigraphy and SPECT/CT: its importance for the sentinel node procedure. AB - PURPOSE: The goal was to evaluate the sentinel node procedure in relation to different pathways of lymphatic drainage and the areas of pelvic lymphadenectomy in patients with prostate cancer assessed by lymphoscintigraphy and SPECT/CT study. METHODS: Eighteen patients with prostate cancer of intermediate prognosis were injected with 240 MBq of (99m)Tc-nanocolloid in the peripheral zone of each quadrant of the prostate, guided by transrectal ultrasonography. Tracer administration was also controlled with a portable gamma camera to assure that there was no diffusion outside the prostate. The injection was followed by planar imaging at 15 min. and 2 h, performing a SPECT/CT study at 2 h. with 2 mm slices. On the same day, a laparoscopic sentinel node lymphadenectomy assisted by a gamma probe and a portable gamma camera was performed. RESULTS: A total of 55 sentinel lymph nodes (SLNs) were visualized. In 17/18 of patients (94%) SLNs were observed outside the obturator region. Twenty SLNs (36%) were observed along the external iliac artery, 14 in the obturator fossa (25.4%), 6 in internal iliac area (11%) and 4 in common iliac region (7.2%). Three SLNs were visualized in presacral (5.4%), paraaortic (5.4%), and pararectal areas (5.4%) and two in paravesical region (3.6%). SLN metastases were found in 6 patients (33%), and in one of them, a SLN located along the common iliac artery, was the only one with metastases. CONCLUSION: Lymphatic drainage from the prostate has high individual variability, and direct drainage outside the pelvic area is observed frequently. With the SLN procedure, SLNs outside the routine area of lymphadenectomy can also be sampled to stage the patient more accurately. PMID- 22055111 TI - Haploidentical haematopoietic stem cell transplantation using CD3 or CD3/CD19 depletion and conditioning with fludarabine, cyclophosphamide and antithymocyte globulin for acquired severe aplastic anaemia. PMID- 22055112 TI - Phase III trial of cetuximab, bevacizumab, and 5-fluorouracil/leucovorin vs. FOLFOX-bevacizumab in colorectal cancer. AB - BACKGROUND: Cetuximab (C), alone or with irinotecan, demonstrates activity in irinotecan-refractory colorectal cancer (CRC). Activity of 5-fluorouracil (5-FU), leucovorin (L), and bevacizumab (B), and preliminary data of cetuximab + bevacizumab, and toxicity profiles suggests that FOLF-CB (5-FU, L, C+B) may have activity with a favorable toxicity profile as first-line therapy. METHODS: Eligible patients were randomized at registration to either arm A (mFOLFOX6-B) (modified, 5-FU. L (folinic acid), oxaliplatin (O) + bevacizumab), administered days 1 and 15 of each 28-day cycle as bevacizumab 5 mg/kg, oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2), and 5-FU 400 mg/m(2) then 1200 mg/m(2)/day for 48 hours, or arm B (FOLF-CB), which included bevacizumab, leucovorin, and 5-FU as in arm A and cetuximab 400 mg/m(2) day 1 cycle 1; all other weekly cetuximab doses were 250 mg/m(2). RESULTS: Two hundred forty-seven patients (arm A/arm B 124/123) were enrolled, and 239 were treated (118/121). Twelve-month progression free survival (PFS) was 45%/32%, objective response rates (ORR) (complete response [CR] + partial response [PR]) were 52%/41%, disease control rates (CR+PR+stable disease [SD]) were 87%/83%, and median overall survival (OS) was 21/19.5 months, respectively. Grade 3-4 neutropenia was higher in arm A (28%/7%), as was grade 3 fatigue (12%/3%), and grade 3 neuropathy (11%/< 1%), whereas acneiform rash was confined to arm B. Retrospective analysis of KRAS mutational status did not demonstrate KRAS as a meaningful determinant of activity, except in arm B patients with KRAS-mutated tumors, which resulted in inferior PFS. Patient satisfaction favored the control (mFOLFOX6-B). CONCLUSION: FOLF-CB was not superior to mFOLFOX6-B in terms of 12-month PFS and ORR, and was not more acceptable to patients. This trial supports the conclusion of other recently reported trials that concurrent cetuximab+bevacizumab should not be routinely used in metastatic CRC. PMID- 22055113 TI - Nonprotein Nitrogen (NPN) and Free amino acid contents of dry, fermented and nonfermented sausages. AB - Fermented and nonfermented sausages were analyzed for concentration changes in total and nonprotein nitrogen (NPN) and in free amino acid profiles during processing. Sausages fermented by Pediococcus pentaceous at 38 degrees C and heated to 60 degrees C had increases (p < 0.05) in total N and NPN contents and increases in concentration (>=5 mg per 100 g dry sample) for 14 of 20 free amino acids. Nonfermented sausages had no increase (p > 0.05) of NPN content and increases in only 6 of 20 free amino acids after heating to 60 degrees C. When the effects of three starter cultures were compared, NPN concentrations after fermentation and heating and after drying were highest to lowest in the following order: P. pentaceous >P. acidilactici with M. varians >P. acidilactici. Variations of free amino acid patterns in the fermented, dried sausages were found which indicated differences in metabolic activity between the cultures. These variations did not (p > 0.05) affect sensory scores for the dried sausages. Overall, these results for rapidly fermented and mildly heated dry sausages were similar to results previously reported for 'European-style' dry sausages processed with prolonged low temperature fermentations. PMID- 22055114 TI - Influence of technological parameters on the structure of the batter and the texture of frankfurter type sausages. AB - The aim of the study was, on the one hand, to determine the relationships between various technological factors, the structure of the batters and the texture characteristics of frankfurter type sausages, and, on the other, to define the possibilities of realizing a reference scale for texture. The addition of sodium chloride in the 0-2% range induces a large increase (60%) in the cooking yield, a decrease in the specific gravity and an increase in the viscosity of the batter determined indirectly through the evolution of the product temperature during chopping. These variations together, give a 30% decrease in the mechanical firmness and a 100% and 90% increase in the juiciness and elasticity of the final products, respectively. However, beyond 2%, sodium chloride does not induce any significant effect on these characteristics. The addition of caseinate in a 1-3% range induces a degassing of the batter and a 10-37% decrease in the water losses during cooking. The higher the caseinate content in the 0-6% range, the larger the rise in the batter temperature during chopping. Sausages are also considered harder (+22%) and less juicy and elastic (-50%) when caseinate content increases. Addition of 0.1-0.5% polyphosphates and chopping under vacuum (0.2 atm) induce variations in the cooking yield, +3% and -1%, respectively, but have no influence on the texture of the final products. Modifications of all these technological parameters induced variations by a factor of 2 in the different mechanical parameters and in parallel differences of 1-2 points on a 6 point scale for sensory characteristics. PMID- 22055115 TI - Effect of a beta-agonist on meat quality and myofibrillar protein fragmentation in bulls. AB - Three experiments were conducted to study the effect of cimaterol on meat quality and myofibrillar protein fragmentation of the Longissimus dorsi muscle. In two experiments (Experiments 1 and 2), conducted with 16 double-muscled Belgian white blue bulls and 15 Charolais bulls, respectively, half of the animals received 60 MUg cimaterol daily per kg liveweight in the diet, during 135 and 93 days, respectively. In a third experiment, 46 normal Belgian white-blue bulls received no or 4 ppm cimaterol in the diet for 246, 127 or 71 days on average. A withdrawal period of 6 days was always applied for cimaterol-treated animals. Ultimate pH, colour and waterholding capacity were not significantly affected. The effect of cimaterol on moisture content was variable, while protein content was increased and fat was reduced. Warner-Bratzler shear force values were increased by cimaterol P < 0.05 in Experiments 2 and 3 and P = 0.07 in Experiment 1). The lower tenderness cannot be explained by differences in sarcomere length or hydroxyproline content. Myofibrillar protein fragmentation was lower when cimaterol was fed, suggesting that cimaterol may reduce myofibrillar protein degradation via a lower activity of the proteolytic enzymes. Length of cimaterol administration only exerted minor effects on meat quality. PMID- 22055116 TI - The effects of conditioning on meat collagen: Part 3-Evidence for proteolytic damage to endomysial collagen after conditioning. AB - The effects of conditioning on the endomysial fraction of bovine meat were investigated. Solubility studies on endomysial connective tissue and analysis of insoluble endomysial fractions remaining after conditioning were carried out. Yields of soluble endomysial fractions represented, on average, 94.5% of total extracted endomysial material for unconditioned muscles compared with 97.5% for conditioned muscles. Soluble endomysial fractions contained, on average, 0.13% collagen from unconditioned muscles and 0.22% collagen from conditioned muscles. The main peptide components observed on analysis of insoluble endomysial fractions after CN Br digestion were derived from types I and III collagen. Changes observed on the peptide maps, evident as the appearance of a number of new bands from conditioned samples, appeared to be muscle specific. The amount of type III collagen relative to type I decreased on conditioning, indicating that endomysial type III collagen was preferentially destroyed during conditioning. Two-dimensional polyacrylamide gel electrophoresis maps revealed new peptide material in the molecular weight range 40 000 to 50 000 on conditioning. These data provide direct evidence of the effect of proteolytic processing on endomysial collagen during conditioning. PMID- 22055117 TI - Utility of immunohistochemical identification of muscle proteins in microstructural studies of comminuted meat products. AB - A series of experiments was conducted in an attempt to immunohistochemically identify specific muscle proteins in raw bovine muscle, meat batters and finely comminuted meat products. Three different antibodies were investigated-monoclonal anti-actin (IgG), polyclonal anti-desmin (IgG) and polyclonal anti-myoglobin (IgM). In addition, the fluorescent compound nitrobenzooxadiazole (NBD) phallacidin was tested. The utility of the antibody anti-desmin proved to be poor. Anti-myoglobin and NBD-phallacidin were useful in muscle tissues that had been technologically treated to a limited extent. Anti-actin reacted with actin present in raw muscle tissue, in muscle samples comminuted with and without additives and in muscle samples that had been comminuted with additives and subsequently heated to 80 degrees C and 115 degrees C. However, its reactivity was markedly more distinct in raw than in processed samples. The utility of current immunohistochemical techniques to study the microstructure of processed meats seems to be limited due to the rapid denaturation of the specific muscle proteins. PMID- 22055118 TI - Effects of added connective tissues on the sensory and mechanical properties of restructured beef steaks. AB - To quantify objectionable levels of connective tissues, restructured beef products were made with 2.5 and 5% added tendon; 5 and 10% added epimysium, gristle, or peri/endomysium; and a control. Initial tenderness (IT), residual connective tissue (CT), and overall texture (OT) were evaluated by a sensory panel. Panelists adversely scored IT, CT, and OT for 2.5 and 5% tendon and CT and OT for 10% epimysium and gristle. CT and OT scores correlated with hydroxyproline content and Lee-Kramer peak shear force for uncooked steaks with added tendon, gristle and epimysium but not peri/endomysium. Acceptable products can be made when raw materials are free of tendons and contain only limited amounts of epimysium. PMID- 22055119 TI - A comparison of DNA-hybridization, immunodiffusion, countercurrent immunoelectrophoresis and isoelectric focusing for detecting the admixture of pork to beef. AB - Using DNA-hybridization at least 0.5% raw pork admixtured to beef could be detected using total genomic pig DNA as well as a cloned pig-specific DNA fragment as a DNA probe. Although signal intensity increased with increasing amounts of pig-DNA, a precise quantitation of pork in samples was not possible. Compared to this the sensitivity for detecting raw pork in beef found by Countercurrent Immunoelectrophoresis was 0.4%; by Immunodiffusion, 1.1%, and by Isoelectric Focusing, 5.0%. PMID- 22055120 TI - Effect of tray liners on the drip loss of lamb chops during retail display. AB - The amount of drip lost by lamb chops during display was affected by the type of tray liner used. In one study involving chilled and frozen/thawed meat, the use of an absorbent paper liner increased the drip loss and influenced whether or not the quantity of drip was affected by freezing/thawing. In another study, thawed chops held for 24 h on plastic coated trays without liner or on a plastic coated liner had less than 2% drip loss, whereas adjacent chops from the same loin processed and held in the same way but displayed on liners of absorbent paper or paper pouches of diatomaceous earth lost 4.3% and 5.6% drip, respectively. This effect of the material in contact with the meat should be considered when reporting drip loss data and when comparing results with those of other researchers. PMID- 22055121 TI - Sulfur transformations in pilot-scale constructed wetland treating high sulfate containing contaminated groundwater: a stable isotope assessment. AB - Current understanding of the dynamics of sulfur compounds inside constructed wetlands is still insufficient to allow a full description of processes involved in sulfur cycling. Experiments in a pilot-scale horizontal subsurface flow constructed wetland treating high sulfate-containing contaminated groundwater were carried out. Application of stable isotope approach combined with hydro chemical investigations was performed to evaluate the sulfur transformations. In general, under inflow concentration of about 283 mg/L sulfate sulfur, sulfate removal was found to be about 21% with a specific removal rate of 1.75 g/m(2).d. The presence of sulfide and elemental sulfur in pore water about 17.3 mg/L and 8.5 mg/L, respectively, indicated simultaneously bacterial sulfate reduction and re-oxidation. 70% of the removed sulfate was calculated to be immobilized inside the wetland bed. The significant enrichment of (34)S and (18)O in dissolved sulfate (delta(34)S up to 160/00, compared to average of 5.90/00 in the inflow, and delta(18)O up to 130/00, compared to average of 6.90/00 in the inflow) was observed clearly correlated to the decrease of sulfate loads along the flow path through experimental wetland bed. This enrichment also demonstrated the occurrence of bacterial sulfate reduction as well as demonstrated by the presence of sulfide in the pore water. Moreover, the integral approach shows that bacterial sulfate reduction is not the sole process controlling the isotopic composition of dissolved sulfate in the pore water. The calculated apparent enrichment factor (E = -220/00) for sulfur isotopes from the delta(34)S vs. sulfate mass loss was significantly smaller than required to produce the observed difference in delta(34)S between sulfate and sulfide. It indicated some potential processes superimposing bacterial sulfate reduction, such as direct re-oxidation of sulfide to sulfate by oxygen released from plant roots and/or bacterial disproportionation of elemental sulfur. Furthermore, 41% of residual sulfate was calculated to be from sulfide re-oxidation, which demonstrated that the application of stable isotope approach combined with the common hydro-chemical investigations is not only necessary for a general qualitative evaluation of sulfur transformations in constructed wetlands, but also leads to a quantitative description of intermediate processes. PMID- 22055122 TI - Rejection of micropollutants by clean and fouled forward osmosis membrane. AB - As forward osmosis (FO) gains attention as an efficient technology to improve wastewater reclamation processes, it is fundamental to determine the influence of fouling in the rejection of emerging contaminants (micropollutants). This study focuses on the rejection of 13 selected micropollutants, spiked in a secondary wastewater effluent, by a FO membrane, using Red Sea water as draw solution (DS), differentiating the effects on the rejection caused by a clean and fouled membrane. The resulting effluent was then desalinated at low pressure with a reverse osmosis (RO) membrane, to produce a high quality permeate and determine the rejection with a coupled forward osmosis - low pressure reverse osmosis (FO LPRO) system. When considering only FO with a clean membrane, the rejection of the hydrophilic neutral compounds was between 48.6% and 84.7%, for the hydrophobic neutrals the rejection ranged from 40.0% to 87.5%, and for the ionic compounds the rejections were between 92.9% and 96.5%. With a fouled membrane, the rejections were between 44.6% and 95.2%, 48.7%-91.5% and 96.9%-98.6%, respectively. These results suggest that, except for the hydrophilic neutral compounds, the rejection of the micropollutants is increased by the presence of a fouling layer, possibly due to the higher hydrophilicity of the FO fouled membrane compared to the clean one, the increased adsorption capacity of hydrophilic compounds and reduced mass transport capacity, membrane swelling, and the higher negative charge of the membrane surface, related to the foulants composition, mainly NOM acids (carboxylic radicals) and polysaccharides or polysaccharide-like substances. However, when coupled with RO, the rejections in both cases increased above 96%. The coupled FO-LPRO system was an effective double barrier against the selected micropollutants. PMID- 22055123 TI - Scanning calorimetric studies of some protein-protein interactions involving myoglobin. AB - To aid in understanding the formation of cooked meat haemoprotein, the thermal denaturation behaviour of metmyoglobin in 0.05(M) phosphate solutions (pH 6.0) of bovine serum albumin and ovalbumin was analysed by differential scanning calorimetry. Although, in general, there is minimal interaction between proteins prior to and during thermal denaturation, it was found that in the presence of an excess of protein of relatively low thermal stability (bovine serum albumin) myoglobin denatures and precipitates with this protein. It is suggested that this destabilisation of myoglobin is due to specific interaction between the denatured protein and the haematin of a conformationally altered, but undenatured, myoglobin. PMID- 22055124 TI - Meat cooking techniques-Part 1: A preliminary study of the effect of the rate of heating in water. AB - In an industrial scale experiment forty hams were deboned, trimmed and defatted. The hams were divided into two random groups of twenty, brined and drained and placed into ham moulds. The two groups were heat treated using a high and low rate (0.60 degrees C/min and 0.12 degrees C/min, respectively) of heating in cooking vats. Both groups were, however, heated to identical internal product temperatures defined as the continuous temperature gradient from thermal centre to product periphery (product thermal gradient). After processing and chilling the individual samples were weighed and evaluated by a sensory panel for juiciness and colour. The results show that heating at lower rates in a water bath can increase yield and improve quality, thus indicating that a kinetic effect of heat independent of final product temperature exists. The results thus justify further investigation into the existence and molecular mechanism of this kinetic effect. PMID- 22055125 TI - Sources and properties of some organisms isolated in two abattoirs. AB - A wide range of organisms was isolated and identified from a number of sites in two abattoirs. Heavily contaminated sites were the water supply to the lairage in one abattoir and animal hair, blood, rumen contents and soil and faecal material from hooves in both abattoirs. Few catalase negative organisms were isolated but other Gram positive organisms included Bacillus spp., coryneforms, M. thermosphactum and coagulase negative cocci. Gram negative organisms were widely distributed in the abattoirs, Pseudomonas spp. being present at most sites, while members of the family Enterobacteriaceae were isolated from all sites except carcass wash water and air samples in the lairages and a boning room. In pure culture 17 of 54 isolates spoiled meat in air at 4 degrees C and 47 at 15 degrees C but under simulated vacuum-package conditions only 7 of 28 at 4 degrees C and 14 of 28 at 15 degrees C gave some indication of spoilage abilities. None of the 10 isolates tested showed marked resistance to chlorine at 20 ppm. PMID- 22055126 TI - Collagen fibrils of the perimysium and endomysium of sheep semitendinosus muscle. AB - Formalin fixed perimysial and endomysial connective tissue was examined morphometrically in terms of collagen fibril composition. The fibril diameter data showed that the endomysial tube collagen fibrils were smaller than the fibrils of the perimysial connective tissue. PMID- 22055127 TI - Effects of pressure treatment on the ultrastructure of striated muscle. AB - Pre- and post-rigor sheep semimembranosus muscles were subjected to a hydrostatic pressure of 100 meganewtons/m(2) at 25 degrees C. The ultrastructure of the muscle fibres was compared with that of non pressure-treated samples. A conspicuous feature of pressure-treated post-rigor samples was the absence of the M-band in the central region of the A-band. Therefore it appeared that some, if not all, of the proteins in the M-line were very susceptible to disaggregation under high pressure. Another feature of the post-rigor pressure-treated sample was the loss of integrity and aggregation of I-band filaments which presumably involved an F-G transformation of actin. Pressure treatment of pre-rigor muscle resulted in extensive structural disruption with contraction band formation. It is suggested that a weakening of thin filaments and M-line bridges, when combined with a pressure-induced contraction, facilitates disruption of pre-rigor pressure treated muscle. PMID- 22055128 TI - Fatty acid composition of backfat in large white pigs selected for low backfat thickness. AB - Samples of midback fat were taken from 157 Large White boars and analysed for fatty acid composition and melting point of lipid. Seventy-seven boars were from a line showing fast efficient growth and low backfat depth (selection line) and 80 from a random-mated control line. All were performance-tested from 27 to 87 kg liveweight on ad libitum feeding. Selection line pigs required 6 % less feed per kilogramme liveweight gain and had thinner backfat at each point of measurement (16-27 %) than the controls but there was no line difference in daily liveweight gain. Selection line pigs had 'eye muscles' which were slightly paler and had a greater drip loss than the controls. The fatty acid composition and melting point of the lipid extracted from backfat was similar between the lines except that the concentration of linoleic acid (C18:2) in both inner and outer layers was some 14% higher in the selection line. There were significant negative correlations between the concentration of C18:2 and the various backfat measurements. Positive correlations were found between some backfat measurements and the concentration of stearic acid (C18:0), particularly in the selection line. Variation in melting point in both layers was more strongly related to variation in the concentration of C18:0 than to that of any other fatty acid. PMID- 22055129 TI - Influence of animal age on the tenderness of beef: Muscle differences. AB - Animal age effects on the mechanical properties of cooked samples from muscles able to cold shorten (Mm. longissimus dorsi, LDA, and semimembranosus, SMA from Achilles tendon hung sides) and muscles partially restrained from shortening (LD muscles from pelvic hung sides, LDP) from groups of animals aged 9, 16, 27 and 42 months were studied. Age effects on stretched muscles (SM muscles from pelvic hung sides, SMP) were determined using groups aged 2 and 120 months in addition to those of 9, 16, 27 and 42 months. Taste panel, Warner-Bratzler shear and Instron compression results for stretched SMP muscles indicated that tenderness decreased systematically as animal age increased. In contrast, Warner-Bratzler peak force values of LDA muscles decreased by half; linearly, as animal age increased from 9 to 423 months, a reflection of less postmortem shortening in samples from the heavier carcasses of older animals. It is suggested that results of age/tenderness studies depend on the age range, differences in carcass weight, the muscle(s) chosen and the cooling rate of muscles and hence on chilling conditions, cooking conditions and the method(s) used to assess the mechanical properties of the cooked muscle(s). PMID- 22055130 TI - Isoelectric variants of actin in raw and cooked meat. AB - Isoelectric focusing of myofibrillar proteins from raw meat gave one major and several minor actin bands. Extending the time, or raising the temperature, of a heat treatment progressively increased the proportion of variants of isoelectric point lower than the primary component. Because of the concomitant release of ammonia on heating, it was concluded that these variants arose from the hydrolysis pf amide groups of asparagine and/or glutamine. Determination of the relative proportion of deamidated actin components may provide a measure of the severity of heat treatment given to a sample of cooked meat. PMID- 22055131 TI - Changes in the microbiological and shelf-life characteristics of beef tongues and livers following transcontinental and transoceanic shipment. AB - The effects of transcontinental (interstate) transport and transoceanic shipment were determined on microbiological and shelf-life characteristics of beef tongues and livers. These variety meats were evaluated for both microbiological and shelf life characteristics following slaughter in Guymon, Oklahoma, USA. The samples were then frozen and sent by refrigerated truck (4.5 degrees C) to storage facilities in Jacksonville, Florida, USA. Further microbiological and shelf-life evaluations took place prior to overseas shipment at the University of Florida and following overseas shipment at The Institute CIVO-Technology, TNO, Zeist, The Netherlands. Aerobic plate counts (APCs) at 35 degrees C for beef tongues showed a significant (P < 0.0.5) decrease following overseas shipment. Similar results were noted for beef livers. For both organs, the surface thawing in Florida, required for sampling, did not appear to affect the final bacterial counts. The 20 degrees C APCs for beef tongues revealed a significant (P < 0.0.5) decrease following interstate transport but not transoceanic shipment. The 20 degrees C APCs for beef livers did not differ significantly during the entire transportation period. The colour differences noted during transport of the product were probably the result of freezing and not of the actual shipping and storage conditions. PMID- 22055132 TI - Yield point in raw beef muscle. The effects of ageing, rigor temperature and stretch. AB - The yield point of raw sternomandibularis muscle of the ox decreased markedly with ageing. This parameter is the most sensitive and selective indicator of ageing since, unlike shear measurements on cooked meat, it is not complicated by heat denaturation or the contribution of the collagen net. Rigor at 2 degrees C with consequent cold shortening has little effect on yield point, but rigor at 37 degrees C diminishes yield values relative to the 15 degrees C controls. Muscles stretched by 40-60% during rigor show higher yield points. Yield was also studied in other muscles. Unaged strips of bull sternomandibularis, or steer psoas and rectus abdominis tended to break rather than yield, but after ageing usually yielded at the same low loads as aged ox sternomandibularis. The histological changes due to yielding varied widely, but stretched, rather than broken, I-bands were the dominant feature. Our interpretation of the electron micrographs is that in rigor muscle, actin filaments fracture while gap filaments stretch, but in aged muscle both sets of filaments fail simultaneously at low loads. PMID- 22055133 TI - A simple, sensitive enzymatic method for quantitation of soya proteins in soya meat blends. AB - A method was developed for the detection and quantitation of soya proteins in soya-meat blends. The procedure involves acid hydrolysis of soya, meat or soya meat blends and determination of free galactose plus arabinose using galactose dehydrogenase. Acetone powders of the various systems were also examined. Average galactose levels in soya flours, soya concentrates and soya isolates were 674,600 and 66 MUM galactose equivalents per gram of product, respectively. Beef and pork contained less than 1 MUM per gram of raw product. The galactose plus arabinose values for soya-meat blends were linearly dependent on the amount of soya added. The method is sensitive and capable of detecting less than 0.2% soya flours or concentrates and less than 2% soya isolates in meat products. PMID- 22055134 TI - Anatomical and joint dissection studies of tissue weight distribution in buffalo bulls and cows: Part 1-Distribution of muscle and bone. AB - Carcasses from six buffalo bulls (slaughtered between 430 and 560 kg liveweight) and six buffalo cows (slaughtered between 405 and 583 kg liveweight) were dissected, the left sides by the anatomical approach, the right sides being jointed and the joints being dissected into fat, muscle, bone and other tissues. Weights of the anatomically dissected muscles and bones, and weights of muscle and bone dissected from each cut, were regressed on weight of the respective tissue in the side. The influence of the animals' sex on tissue distribution was investigated using a one-way analysis of covariance. Results were consistent with those reported on cattle in that (i) sex had no influence on the amount of total muscle occurring in the distal parts of limbs or surrounding the spinal column and connecting the fore limb to the thorax and neck, (ii) females had more of their total muscle in the flank or abdominal wall and less in the loin than males, and (iii) females tended to have less of their total side bone in the appendicular skeleton and more in the axial skeleton than males. However, the influence of the animal's sex on the amount of total muscle in the proximal parts of its limbs was significant in buffaloes but not in cattle; the reverse was true for the muscle group of the thorax and neck. The overall sex differences in bone weight distribution for buffaloes were as small as previously reported for cattle, sheep and pigs. Features of better muscle-weight distribution in buffalo males as compared with females and in Egyptian buffaloes as compared with Australian buffaloes and British cattle breed types are discussed. PMID- 22055135 TI - Anatomical and joint dissection studies of tissue weight distribution in buffalo bulls and cows: Part 2-Fat partition and distribution. AB - Six buffalo bulls and six buffalo cows were slaughtered between, respectively, 430-560 kg and 405-585 kg liveweight. Sex differences in fat partition and distribution were examined using one-way analyses of covariance on data converted to logarithms. Buffalo bulls and cows showed no significant differences in the partition of total body fat between the carcass and the offal or between the different components of the total carcass fat (subcutaneous, SCF; intermuscular, IMF; kidney and channel, KCF) and those of the total offal fat (caul; mesenteric; heart). In addition, no significant differences between bulls and cows were detected with respect to the partition of the entire side fat between its component depots (SCF; IMF; KCF) and the partition of the dissected side fat (DSF) between its elements (SCF; IMF). Bulls did not differ significantly from cows in the distribution of IMF between cuts. However, bulls had more of their total SCF in the buttock cuts (P < 0.05) and pistol (P < 0.001) and BLRC (P < 0.01) expensive cut groups, while cows had more weight of total SCF contained in the flank (P < 0.05) and the 7th-10th rib (P < 0.01). The weight of total DSF was greater (P < 0.05) in the buttocks of bulls and (P < 0.01) in the flanks of cows. PMID- 22055136 TI - Effect of breeding bull on the fatty acid composition of the carcass lipid in steers of a beef breed cattle. AB - Samples of neutral lipid were taken from the carcasses of forty-eight Japanese Black steers, the progeny from three breeding bulls, on similar planes of nutrition and of the same age, and were analysed for fatty acid composition. The breeding bull seems to significantly affect the fatty acid composition of the lipid from the thoracic subcutaneous fatty tissue and the inter- and intra muscular fatty tissues of the Longissimus dorsi muscle. No significant correlation between breeding bull and fatty acid composition of perinephric fatty tissue was found. There was an increase in total concentration of unsaturated fatty acids from internal to external sample locations. PMID- 22055138 TI - Protein food supplements: Recent advances Edited by M. A. Maltz, Noyes Data Corporation, Park Ridge, NJ, USA. 1981. Price not quoted. PMID- 22055137 TI - Protein hydrolysates from meat industry by-products. AB - Hydrolysates were prepared from bovine lung, bovine rumen and from partially defatted tissue by treatment at 50 degrees C with either pepsin at pH 3.0, papain at pH 5.5, neutrase at pH 7.0 or alcalase at pH 8.5. For all substrates papain was the most effective hydrolysing agent of those studied whilst neutrase was the least effective. Yields of soluble hydrolysate were high with 45-85 % of the protein being solubilised. In addition, the tissue is, to some extent, defatted during hydrolysis. All enzymes, with the exception of alcalase, readily solubilised the collagen of heated by-products although undenatured (unheated) collagen was, to some extent, resistant to enzymic digestion. Amino acid analysis of the soluble hydrolysates indicated that there was no major loss of any amino acid following prolonged enzymic hydrolysis. In addition, no increase in tyramine concentration occurred during hydrolysis. PMID- 22055140 TI - Emergency department visits due to vertebral fractures in the Netherlands, 1986 2008: steep increase in the oldest old, strong association with falls. AB - BACKGROUND: Vertebral fractures are a common consequence of osteoporosis in older persons. With the ageing of the population, numbers are expected to rise. OBJECTIVE: To determine trends in health care demand due to vertebral fracture related emergency department (ED) visits and hospitalizations in the older Dutch population. DESIGN AND SETTING: Secular trend analysis of vertebral fracture related ED visits between 1986 and 2008, using the Dutch Injury Surveillance System. All ED visits with a primary diagnosis of a vertebral fracture in persons aged >=65 years were extracted from this database. MAIN OUTCOME MEASURE: Numbers, age-specific and age-adjusted incidence rates (per 100,000 population) of ED visits and hospitalization rates due to vertebral fractures in the older Dutch population were calculated for each year of the study. RESULTS: The total number of ED visits due to a vertebral fracture increased from 913 in 1986 to 2502 in 2008 (174% increase). The majority of fractures were caused by a low-energetic fall incident (83%). The overall age-adjusted incidence rate increased from 51.6 per 100,000 population in 1986 to 103.6 in 2008. Incidence rates increased with age and were higher in females than in males. The hospitalization rate remained stable at about 50-55%, in both females and males. CONCLUSION: Vertebral fracture related ED visits and hospitalizations are increasing rapidly in the older Dutch population, especially in the oldest-old. Most vertebral fractures were associated with falls. These findings indicate that a pro-active approach in the diagnosis and treatment of osteoporosis and in the prevention of falls in both men and women is warranted. PMID- 22055139 TI - Effects of penehyclidine hydrochloride on pulmonary contusion from blunt chest trauma in rats. AB - BACKGROUND AND OBJECTIVE: Toll-like receptor 4 (TLR4) is widely recognised as a pattern recognition receptor (PRR) in the triggering of innate immunity. Lung inflammation and systemic innate immune responses are dependent on TLR4 activation undergoing pulmonary contusion. Therefore, the author investigated the effects of penehyclidine hydrochloride (PHC) on the expression of TLR4 and inflammatory responses of blunt chest trauma-induced pulmonary contusion. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were randomly assigned into three groups: normal control (NC) group, pulmonary contusion (PC) group and penehyclidine hydrochloride treatment (PHC) group. Pulmonary contusion was induced in anesthetised rats at fixed chest impact energy of 2.45J. Lung injury was assessed by the histopathology changes, arterial blood gas and myeloperoxidase (MPO) activity of lung. The serum tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assays (ELISA). The expression of TLR4 was determined by immunohistochemistry. RESULTS: Blunt chest trauma produced leucocytosis in the interstitial capillaries, hypoxemia, and increased MPO activity. The expressions of TNF-alpha, IL-6 and TLR4 in the lung were significantly enhanced during pulmonary contusion. PHC treatments effectively attenuated pulmonary inflammation responses, as shown by improved pulmonary oxygenation, histopathology damage, decreased the MPO activity, the expressions of TNF-alpha, IL-6, and TLR4 after lung injury. CONCLUSION: It might be concluded that PHC exhibit anti-inflammatory and protective effects in traumatic lung injury via the inhibition of the TLR4 pathway. PMID- 22055141 TI - Radiation exposure in whole-body computed tomography of multiple trauma patients: bearing devices and patient positioning. AB - BACKGROUND: Whole-body computed tomography (WBCT) plays an important role in the management of severely injured patients. We evaluated the radiation exposure of WBCT scans using different positioning boards and arm positions. METHODS: In this retrospective study, the radiation exposure of WBCT using a 16-slice multislice computed tomography scanner was evaluated. Individual effective doses (E, mSV) was calculated. Patients were assigned to two groups according to placement on a plastic transfer mat (PTM, group 1) or on the Trauma TransferTM-Board (TTB, group 2). Data were collected for each group with arm placement on the abdomen (a) or in raising position (b), respectively. The maximum ventro-dorsal diameter [VDD] at the trunk was measured. RESULTS: 100 patients with potentially life threatening injuries were analysed. Patient demographics and VDD did not differ in the two groups. Radiation exposure in term of E did not reveal any significant differences between the two positioning boards using same arm position [group 1a (n=26) vs. 2a (n=24) (mSV): 16.7+/-4.7 vs. 17.1+/-4.4, group 1b (n=26) vs. 2b (n=24) (mSV): 13.1+/-3.9 vs. 14.3+/-1.5]. The arm raising positioning showed a significant reduction in E in comparison to the placement on abdomen position [group 1b vs. 1a (mSV): 13.1+/-3.9 vs. 16.7+/-4.7, p<0.05, group 2b vs. 2a (mSV): 14.3+/-1.5 vs. 17.1+/-4.4, p<0.05]. CONCLUSIONS: Patient arm positioning for WBCT has an important influence on radiation exposure. Effective dose was 16-22% lower when arms were raised. An individual placement algorithm may lead to a relevant reduction of radiation exposure of severely injured patients. PMID- 22055142 TI - Relationships between bacon grade schedules and carcass characteristics. AB - A computer model was used to compare alternative bacon grade schedules in terms of the carcass composition, joint proportions and simple meat quality characteristics (muscle pH and light reflectance) of pigs in different grades. The data used were for 350 side-dissected carcasses from years 6 to 8 of the Meat and Livestock Commission's Commercial Pig Evaluation. Analyses were carried out separately for restricted-fed and ad libitum-fed pigs. Overall means and standard deviations for carcass weight and lean percentage were 64.4 +/- 3.19 and 51.5 +/- 3.98 (restricted) and 65.1 +/- 3.57 and 49.9 +/- 4.09 (ad libitum). Alternative schedules were compared against a base schedule, typical of commercial practice in Great Britain and involving the following requirements for the principal grade: a maximum P(2) measurement (taken laterally over the M. longissimus) of 15 mm, maximum mid-line fat measurements (shoulder/loin) of 42 22 mm and a minimum side length of 770 mm. Removal of the shoulder/loin and length requirements increased the proportion of pigs in the principal grade by seven percentage units with little effect on the mean carcass characteristics of pigs in the grade. An extreme tightening of the maximum shoulder/loin measurements to 35 15 mm removed half the pigs from the principal grade and increased the mean carcass lean content and the lean content of individual joints for pigs in the grade by one to two percentage units. Introduction of a minimum muscle thickness measurement of 55 mm had a similar effect. In both cases the effect was partially mediated through a general reduction in fatness and could be achieved by tightening the maximum P(2) fat thickness. None of the changes in grade schedules examined materially altered the mean meat quality characteristics of pigs in the principal grade. The analysis illustrates the complexities involved in using grade thresholds based on a number of correlated measurements. The use of a multiple regression approach, in which carcass lean content and commercial value are estimated from measurements known to contribute significantly to the regression, would simplify the situation considerably. PMID- 22055143 TI - Scanning calorimetric studies on offal protein isolates. AB - Differential scanning calorimetry was performed on protein isolated from bovine lung and rumen. Isolates defatted with solvents of increasing polarities (petroleum ether, carbontetrachloride, chloroform, dichloromethane, isopropanol, ethanol and methanol) presented very similar phase transitions. The thermograms of the original, non-defatted rumen isolates exhibited phase transitions which recovered completely after incubation at 303-313 K. This reversible effect was not noticed after petroleum ether extraction. Mixture and incubation at 313 K of the defatted proteins and the extracted fat fraction failed in reproducing the reversibility observed. PMID- 22055144 TI - Phospholipase A(2) activity, calmodulin, Ca(2+) and meat quality in young and adult halothane-sensitive and halothane-insensitive British Landrace pigs. AB - PSE (pale, soft and exudative) meat is the result of a developmental disorder and is not produced in meat from young (3-11 weeks) halothane-sensitive British Landrace pigs. Formation of the PSE condition is closely associated with the muscle mitochondrial phospholipase A(2) activity, which increases significantly from 12 weeks of age. The increase in phospholipase A(2) activity shows good correlation (r = 0.87) with the increase in post-mortem sarcoplasmic Ca(2+). In halothane-insensitive British Landrace both the phospholipase A(2) activity and sarcoplasmic Ca(2+) level remain constant throughout growth. Significant increases in the levels of endogenous mitochondrial calmodulin, fatty acids and phospholipase A(2) activity, and Ca(2+) (mitochondrial and sarcoplasmic) are observed in the M. longissimus dorsi of adult halothane-sensitive pigs when compared with either young halothane-sensitive or young and adult halothane insensitive pigs. The enhanced mitochondrial phospholipase A(2) activity is calmodulin-dependent and the increase in activity is postulated to be due to increased endogenous calmodulin. PMID- 22055145 TI - The effects of sex condition, genotype and diet on bovine muscle fiber characteristics. AB - The effects of sex condition, breed type and dietary energy level on muscle fiber characteristics were examined at various ages and related to carcass characteristics and meat palatability. Cattle fed a low-energy diet had a significantly higher percentage of red muscle fibers, larger white muscle fiber areas and a greater percentage area of red muscle fibers than cattle fed a high energy diet. A significant sex * breed within slaughter group interaction existed, which was complicated due to differences within breeds and sexes at different points of physiological maturity. Separate correlation coefficients for bulls and steers are shown that suggest strong directional interactions between carcass characteristics and meat quality, and muscle fiber characteristics. PMID- 22055146 TI - Contribution of bone marrow to the vitamin content of mechanically separated meat. AB - Vitamin A and C content of red marrow from vertebrae of Good and Choice grade steers was determined so that the nutritional contribution of marrow to mechanically separated meat (MSM) could be more fully defined. Vitamin A and C values for marrow were higher than those reported for muscle but the slightly higher levels in MSM than in hand boned meat are nutritionally insignificant. PMID- 22055147 TI - Sequencing of agents for metastatic renal cell carcinoma: can we customize therapy? AB - CONTEXT: The expanding armamentarium of agents for the therapy of advanced clear cell renal cell carcinoma (RCC) warrants further investigation of optimal patient selection. OBJECTIVE: To analyze the second and subsequent line of targeted therapies for advanced RCC while integrating clinical and molecular markers and imaging. EVIDENCE ACQUISITION: Data were acquired from research published in peer reviewed literature or presented at major conferences. EVIDENCE SYNTHESIS: Following first-line vascular endothelial growth factor (VEGF) inhibitors, second line therapy with everolimus, a mammalian target of rapamycin inhibitor, and axitinib, a VEGF receptor tyrosine kinase inhibitor, have demonstrated benefits in progression-free survival (PFS). Sorafenib, pazopanib, and axitinib have demonstrated extension of PFS following cytokines. Optimal patient selection based on biomarkers is undergoing investigation. Clinical trials evaluating novel agents and combinations should be preferred. CONCLUSIONS: Currently, the sequence of therapy is based on patient and physician decision, which may be influenced by comorbidities and toxicity profiles. PMID- 22055148 TI - An immunological method to assess protein degradation in post-mortem muscle. AB - A method for determining proteolysis of any specific protein in muscle is demonstrated. The protocol involves the preparation of a specific antibody which is used in immunoblotting total protein extracts from post-mortem muscle. In the present study an antibody to bovine myosin heavy chain was prepared that reacts with intact myosin heavy chain as well as proteolytic fragments that are generated by proteases. We show that little, if any, myosin heavy chain fragments are generated during prolonged aging of muscle at 4 degrees C. In contrast, storage of muscle at 37 degrees C results in the rapid breakdwon of myosin heavy chain to immunologically detectable peptides. Using a monoclonal antibody to titin, we demonstrate that this protein is degraded at 4 degrees C during the aging period, and that, between 2 and 3 weeks following slaughter, no undergraded titin is detectable. This method is suitable for the analysis of any protein that can be separated by SDS polyacrylamide gel electrophoresis (SDS-PAGE). PMID- 22055149 TI - The effect of oestrus behaviour on muscle glycogen concentration and dark-cutting in beef heifers. AB - Preliminary observations at an abattoir showed an association between oestrus behaviour and dark-cutting in beef. Two follow-up experiments examined the relationship between oestrus behaviour and muscle glycogen content, carcass bruising and meat ultimate pH. In the first experiment heifers in oestrus were compared with controls in mid-cycle. Oestrus was associated with a loss of glycogen in M. longissimus dorsi. Also plasma creatine kinase activity increased, reflecting bruising or strenuous muscle activity. In the second experiment heifers were slaughtered during oestrus. On the basis of pre-slaughter behaviour they were assigned to active or inactive groups, which subsequently yielded 39% and zero dark-cutting carcasses, respectively. Loss of muscle glycogen was accounted for by the number of times an animal mounted (r = -0.85). Likewise, variation in meat ultimate pH was associated with mounting activity (P < 0.001). Carcass bruising was higher in the active group (P < 0.0.001) and the main cause of bruising was being mounted (r = 0.74). It was concluded that single penning of oestrus heifers to eliminate mounting activity would reduce the incidence of dark cutting. PMID- 22055150 TI - Pig carcass classification in the 65-190 kilogram range using the Danish fat-o meat'er. AB - A study was carried out in which 200 pig carcasses were selected in such a way as to cover the most complete range of dead weights and lean contents available on the market in Italy. Left sides were probed for fat thickness and muscle depth at 2 3 , 3 4 and 4 5 LR (last rib) at 7, 9 and 11 cm off the dorsal midline. Fat thickness was also measured at 3 4 and 4 5 LV (last lumbar vertebrate) at 8 and 10 cm off the dorsal midline and, on the dorsal midline, on the middle of the gluteus medius muscle, at the last rib and at the shoulder. Right sides were cut according to the standard 'Parma jointing method' within 1 h post mortem while left sides were cut with a partially modified 'Parma jointing method' after overnight chilling. Each joint of the first 120 left sides was weighed and separated into subcutaneous and intermuscular fat, bone and meat to establish meat content. The results were used to fix a partial dissection formula which was employed for 74 of the remaining sides while 6 were totally dissected to verify the formula. PMID- 22055151 TI - The effect of the initial gas volume to meat weight ratio on the storage life of chilled beef packaged under carbon dioxide. AB - Normal pH (5.5-5.7) and high pH (>6.0) beef cuts of 400 g were vacuum packaged in polyvinylidine chloride (PVDC) laminate, in aluminium foil laminate or in foil laminate with a CO(2) scavenger (Ba(OH)(2)); or were packaged under CO(2) in foil laminate with CO(2) added at 200, 400, 700, 1000 or 2000 ml per kg of meat. The process used to prepare meat before packaging resulted in an initial flora containing a high fraction of eneterobacteria but with undetectable numbers of lactobacilli. During storage at +1 degrees C, all vacuum packaged meat developed floras containing substantial fractions of enterobacteria. The enterobacteria fractions were larger on high pH than on normal pH meat, and on normal pH meat in PVDC or in foil laminate plus CO(2) scavenger packs than on normal pH meat in foil laminate without the CO(2) scavenger. All vacuum packaged meat was spoiled by putrid flavours, high pH meat at 7 weeks and normal pH meat at 12 weeks. Increasing amounts of added CO(2) progressively retarded the development of putrid spoilage, as growth of the spoilage floras was slowed while the relative numbers of lactobacilli in the floras were enhanced. With the two largest amounts of added CO(2), spoilage was delayed until 15 weeks and 21 weeks for high pH meat and normal pH meat, respectively, and enterobacteria were detected in the spoilage floras only at later sampling times. With lesser amounts of added CO(2), enterobacteria persisted or re-emerged at earlier times, in the floras. PMID- 22055152 TI - The solubility of carbon dioxide in meat. AB - The solubility of CO(2) in muscle tissue of pH 5.5 at 0 degrees C was approximately 960 ml at STP/kg of tissue. The solubility increased with increasing tissue pH by 360 ml/kg for each pH unit. The solubility decreased with increasing temperature by 19 ml/kg for each degrees C rise. Solubilities in beef, pork and lamb muscle tissue were comparable. The solubility of CO(2) in fat tissues initially increased as the temperature was raised above 0 degrees C, but then declined at higher temperatures, with the temperature of peak solubility and the solubility curves being markedly different for fat tissue from the three species. PMID- 22055153 TI - Stabilization of meat lipids with nitrite-free curing mixtures. AB - Several nitrite-free meat-curing mixtures have been formulated. The mixtures included salt, sugar, ascorbates, an antioxidant and/or a chelator, an antimicrobial agent and dinitrosyl ferrochemochrome (DNFH). They imparted to meat a similar oxidative stability as that of sodium nitrite. Butylated hydroxyanisole and t-butylhydroquinone were the best anti-oxidants and polyphosphates, ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid were the superior chelators. The antimicrobial agents used were potassium sorbate, propryl paraben, fumarate esters and sodium hypophosphite. In the above mixtures, the added effect of (DNFH) on oxidative stability of the cooked meats was similar to the added effect of 150 ppm sodium nitrite. PMID- 22055155 TI - Long-term monitoring and modeling of the mass transfer of polychlorinated biphenyls in sediment following pilot-scale in-situ amendment with activated carbon. AB - The results of five years of post-treatment monitoring following in-situ activated carbon (AC) placement for stabilization of polychlorinated biphenyls (PCBs) at an inter-tidal mudflat adjacent to Hunters Point Shipyard, San Francisco Bay, CA, USA are reported in this paper. After five years, AC levels of the sediment cores were comparable to those at earlier sampling times. Passive sampler uptake validated the benefit of the AC amendment with a strong local sorbent dose-response relationship. The PCB uptakes in passive samplers decreased up to 73% with a 3.7 dry wt.% AC dose after five years, confirming the temporal enhancement of the amendment benefit from a 19% reduction with a 4.4% dose observed within one month. The long-term effectiveness of AC, the local AC dose response, the impact of fouling by NOM, the spatial heterogeneity of AC incorporation, and the effects of advective sediment pore-water movement are discussed with the aid of a PCB mass transfer model. Modeling and experimental results indicated that the homogeneous incorporation of AC in the sediment will significantly accelerate the benefit of the treatment. PMID- 22055156 TI - Impact of mineral micropores on transport and fate of organic contaminants: a review. AB - Nanometer-scale pores are abundant in porous geological media (soils, sediments, and aquifer materials), and may account for over >90% of total mineral surface areas. Sorption of organic contaminants in mineral micropores (<2 nm) plays a key role in controlling their fate and transport when the porous geological media have very low organic carbon contents (<0.1%). Significant adsorption of hydrophobic organic contaminants could only occur in the hydrophobic micropore spaces because of the strong competition from water. The rate of desorption from micropores is very slow due to hindered diffusion, resulting in distinct two stage desorption behavior for microporous solids. Size exclusion effect prevents micropore-sorbed contaminants from being accessed by microorganisms and their extracellular enzymes, thus reducing their bioavailability and biodegradation rates. Results from recent studies indicate that sorption in micropores can also inhibit abiotic degradation of reactive contaminants by protecting them in confined spaces with little reactive water, slowing down hydrolysis and other water-mediated transformations. As a result of the inhibitory effect on abiotic and biotic transformations, and the slow desorption due to hindered diffusion, sorption in hydrophobic micropores of porous geological media can cause preservation of anthropogenic organic contaminants in the subsurface and may increase their persistence to the time scale of geological ages under appropriate conditions. From a practical perspective, understanding the role of mineral micropores is important in assessing the long-term ecotoxicological risk of organic contaminants in the subsurface and designing remediation strategies. PMID- 22055157 TI - Combining experimental techniques with non-linear numerical models to assess the sorption of pesticides on soils. AB - The risk assessment of groundwater pollution by pesticides may be based on pesticide sorption and biodegradation kinetic parameters estimated with inverse modeling of datasets from either batch or continuous flow soil column experiments. In the present work, a chemical non-equilibrium and non-linear 2 site sorption model is incorporated into solute transport models to invert the datasets of batch and soil column experiments, and estimate the kinetic sorption parameters for two pesticides: N-phosphonomethyl glycine (glyphosate) and 2,4 dichlorophenoxy-acetic acid (2,4-D). When coupling the 2-site sorption model with the 2-region transport model, except of the kinetic sorption parameters, the soil column datasets enable us to estimate the mass-transfer coefficients associated with solute diffusion between mobile and immobile regions. In order to improve the reliability of models and kinetic parameter values, a stepwise strategy that combines batch and continuous flow tests with adequate true-to-the mechanism analytical of numerical models, and decouples the kinetics of purely reactive steps of sorption from physical mass-transfer processes is required. PMID- 22055158 TI - Stable carbon and hydrogen isotope fractionation of dissolved organic groundwater pollutants by equilibrium sorption. AB - Linear free energy relationships (LFERs) were established which relate equilibrium vapor-liquid isotope effects to stable carbon and hydrogen isotope enrichment factors for equilibrium sorption to geosorbents. The LFERs were established for normal, cyclic or branched alkanes, monoaromatic hydrocarbons, and chloroethenes. These LFERs predict that isotopic light compounds sorb more strongly than their heavy counterparts. Defining fractionation as in classical literature by "heavy divided by light", carbon enrichment factors for equilibrium sorption were derived which ranged from -0.13+/-0.040/00 (benzene) to -0.52+/ 0.190/00 (trichloroethene at 5-15 degrees C). Hydrogen enrichment factors for sorption of 14 different compounds were between -2.4 and -9.20/00. For perdeuterated hydrocarbons the predicted enrichment factors ranged from -19+/ 5.40/00 (benzene) to -64+/-300/00 (cyclohexane). Equilibrium sorption experiments with a soil and activated carbon as sorbents were performed in the laboratory for perdeuterocyclohexane and perdeuterotoluene. The measured D/H enrichments agreed with the LFER prediction for both compounds and both sorbents within the uncertainty estimate of the prediction. The results of this work suggest that equilibrium sorption does create only very small isotope shifts for (13)C in groundwater pollutants in aquifers. It is also suggested that deuterium shifts are expected to be higher, especially for strongly sorbing pollutants. PMID- 22055159 TI - An interdisciplinary approach to the prevention and treatment of groin wound complications after lower extremity revascularization. AB - BACKGROUND: If not effectively treated, groin wound infections following lower extremity revascularization (LER) may result in graft or limb loss. METHODS: A retrospective review was performed of all patients who underwent muscle flap transposition by a single surgeon after LER between 2006 and 2010. RESULTS: Twenty-nine muscle transposition flaps were performed in 24 patients (21 sartorius, 6 rectus femoris, and 2 gracilis). Nineteen were for treatment of groin wound infections, two for treatment of lymphocele, one for coverage of exposed graft in the setting of pyoderma gangrenosum, and seven for infection prophylaxis. Two graft losses followed flap placement. The limb loss rate was 4%. When performed for therapeutic purposes, graft salvage rates were 100% for autogenous and 92% for synthetic grafts. CONCLUSIONS: Muscle transposition flaps are an effective means of graft salvage in the setting of groin wound complications following LER and should be considered for infection prophylaxis in high-risk patients. PMID- 22055162 TI - Radiation preservation of meat and meat products: A review. AB - The World Health Organisation (WHO) in 1980 clarified the position regarding the medical acceptability of irradiated foods when it said'...no health hazard results from consuming any food irradiated up to a dose of one megarad (1 Mrad)'. This resulted in renewed interest in irradiation as a cost-effective alternative to traditional preservation methods such as canning and freezing. Thus, radurisation (the application of ionising radiation at a dose level which substantially reduces the microbial population) increases the shelf life of poultry, comminuted meat and meat dishes significantly. Low dose irradiation, or radicidation, eliminates parasites such as Trichinae and cysticerci in pork and, very importantly, salmonella organisms in poultry and red meat. Therefore, irradiation has an important role to play in public health protection. High dose irradiation, or radappertisation ('cold sterilisation'), uses doses in excess of 1 Mrad and is analogous to retorting as understood in the canning industry. However, it can adversely affect quality in producing 'free radicals' in high protein foods such as meat. To prevent this, special precautions are necessary, e.g. irradiation is conducted at very low temperatures and the product is usually vacuum packed. A further potential use of irradiation is its ability to reduce the quantity of nitrite necessary in cured meats. This may become of practical significance if legislation further reduces the amount of nitrite permitted in these products. PMID- 22055160 TI - Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1. AB - Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 * 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 * 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 * 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression. PMID- 22055161 TI - Redundant amodal properties facilitate operant learning in 3-month-old infants. AB - The current study examined the role redundant amodal properties play in an operant learning task in 3-month-old human infants. Prior studies have suggested that the presence of redundant amodal information facilitates detection and discrimination of amodal properties and potentially functions to influence general learning processes such as associative conditioning. The current study examined how human infants use redundant amodal information (visual and haptic) about the shape of an object to influence learning of an operant response. Infants learned to kick to move a mobile of cylinders while either holding a cylinder, a rectangular cube, or no object. Kick rate served as the dependent measure. The results showed that infants given matching redundant amodal properties (e.g., viewed cylinders while holding a cylinder) showed facilitated operant learning whereas infants given mismatching redundant amodal properties showed inhibited operant learning. These results support and extend the Intersensory Redundancy Hypothesis by demonstrating that amodal redundancy influences complex learning processes such as operant conditioning. PMID- 22055163 TI - Hydrolysis of the sarcoplasmic, myofibrillar and connective tissue proteins of lean beef by alcalase and its relationship to whole meat hydrolysis. AB - The enzymic hydrolysis and solubilisation of the three meat protein fractions have been investigated in order to elucidate some aspects of the hydrolysis of whole beef protein. Much of the water-soluble sarcoplasmic protein fraction was insolubilised on heating for 25 min at 60 degrees C. While most of this insoluble protein was easily resolubilised enzymically, some of it remained insoluble after 5 hours' hydrolysis. Solubilisation of connective tissue by Alcalase after a 3 h reaction increased markedly from 23% at 55 degrees C to 99% at 60 degrees C. This explains the high optimum temperature for solubilisation of whole beef by Alcalase. A significant portion of myofibrillar tissue remained insoluble after 3 hours' reaction. indicating that the majority of the insoluble solids remaining after whole meat hydrolysis at 60 degrees C derived from myofibrillar tissue. There was good agreement between an experimental reaction progress curve for whole beef hydrolysis and one estimated from progress curves for hydrolysis of the three meat protein fractions. PMID- 22055164 TI - Hygienic aspects of porcine gullets. AB - In an attempt to elaborate good manufacturing practices, including the collection, processing and storage of porcine gullets, their bacterial condition immediately after collection (100 samples), as well as that of deep frozen gullets just before incorporation into meat products (40 samples), was assessed. Fresh gullets were found to be contaminated to a high degree: poured plate colony count at 30 degrees C (PPCC) approximately 10(6) to 10(7) and Enterobacteriaceae approximately 10(3) to 10(4) cfu g(-1). Deep frozen gullets showed even higher counts: PPCC approximately 10(7) to 10(8) and Enterobacteriaceae approximately 10(4) to 10(5) cfu g(-1). Hygiene during collection was visually assessed in six abattoirs and found to be satisfactory in two, moderate in three and poor in one. The effects of processing, by cleaning or removal of the mucus membrane, on bacterial condition, pH, colour and odour were assessed before and during storage at 4 degrees C and 20 degrees C. Both cleaning and removal of the mucus membrane resulted in up to approximately a tenfold reduction of colony counts. After 7 days' storage at 4 degrees C these were significantly lower than those of unprocessed gullets (P < 0.01). Processed gullets stored at 4 degrees C were no longer fit for consumption after 4 days' storage. It being impossible to achieve a marked improvement in the bacteriological condition of gullets, the incorporation of these products into sausages should be discouraged and their use in petfoods only allowed under reasonable conditions of hygiene and chilling. PMID- 22055165 TI - Practical observations on the methodology for determining 3-methyl-l-histidine using fluorescamine derivatives. AB - The method for the detection and possible quantification of the unusual amino acid 3-methyl-l-histidine has been refined and elucidated. This is an essential prerequisite for the determination of its value as a robust unequivocal index of lean meat protein. PMID- 22055166 TI - Protein quality control in the ER: balancing the ubiquitin checkbook. AB - Protein maturation in the endoplasmic reticulum (ER) is subject to stringent quality control. Terminally misfolded polypeptides are usually ejected into the cytoplasm and targeted for destruction by the proteasome. Ubiquitin conjugation is essential for both extraction and proteolysis. We discuss the role of the ubiquitin conjugation machinery in this pathway and focus on the role of ubiquitin ligase complexes as gatekeepers for membrane passage. We then examine the type of ubiquitin modification applied to the misfolded ER protein and the role of de-ubiquitylating enzymes in the extraction of proteins from the ER. PMID- 22055167 TI - [Intestinal pseudo-obstruction in Steinert myotonic dystrophy: a clinical radiological description of 2 cases]. PMID- 22055168 TI - HEMS simulator training for safety and clinical proficiency. Letter. PMID- 22055170 TI - Helicopter scene response for a STEMI patient transported directly to the cardiac catheterization laboratory. AB - At 2:10 pm, a 40-year-old Caucasian woman with no known medical history called 911 complaining of substernal, crushing chest pain that had started 2 to 3 hours before she called emergency medical services (EMS). EMS arrived at 2:24 pm and obtained a 12-lead electrocardiogram (ECG) diagnostic of ST-segment elevation myocardial infarction (STEMI) at 2:36 pm. University Air Care was requested by local EMS at 2:42 pm to respond directly to the cardiac scene in rural Ohio for rapid transport to a facility capable of performing percutaneous coronary intervention (PCI). The closest PCI-capable facility was approximately 35 minutes away by ground or 13 minutes by air. The closest non-PCI hospital was approximately 20 minutes away by ground (Fig. 1). PMID- 22055172 TI - Mother's little helper: the problem of narcotic diversion. PMID- 22055174 TI - Air medical evacuations from a developing world conflict zone. AB - Somalia has been without effective government for close to two decades, with more than 1 million people internally displaced. The political unrest persists, with United Nations-backed African Union peacekeeping forces supporting the Transitional National government of Sharif Ahmed, struggling to maintain control of central Mogadishu from Islamist extremist groups, such as the reportedly Al Qaeda-backed Al-Shabab. The African Union force of 5,000 troops is predominantly of Ugandan and Burundian origin, making up the African Mission in Somalia (AMISOM) effort. However, its mandate is limited to operations only in Mogadishu, and it is unauthorized to actively pursue insurgents. As with other ongoing high profile conflicts, African Union troops face an enemy that blends into the civilian populace, fighting with a lethal mixture of improvised explosive devices and suicide bombers. PMID- 22055175 TI - Influence of helicopter flight on temperature of helicopter EMS crewmembers. AB - INTRODUCTION: Thermoregulation of critically ill patients during helicopter emergency medical service (HEMS) transport can be influenced by the flight, increasing the risk of hypothermia. However, the literature is unclear as to whether temperature decrease among those patients is affected by the flight itself or by the patients' clinical status and therapies. We evaluated the effect of helicopter flight on the body temperature of the healthy members of the HEMS crew of the Friuli Venezia Giulia region, Italy. METHODS: From August 12 to September 3, 2009, and from February 12 to April 1, 2010, tympanic temperature was measured, on a voluntary basis, before and after the flight among the crewmembers. The effect of flight and personal characteristics on temperature after the flight was analyzed through multivariate regression. RESULTS: Ninety five records were analyzed. On average, the temperature increased by 0.2 +/- 0.5 degrees C. In 29.5% of the cases, however, it decreased. The only factors that were significantly associated with the temperature after the flight were temperature at liftoff and mountain rescue flights. CONCLUSION: Among healthy subjects, the helicopter vibrations may induce an increase in body temperature. Small sample size and lack of information on a number of potential confounders prevented the identification of the possible determinants of a temperature decrease among some subjects. PMID- 22055176 TI - Australian dust storm: impact on a statewide air medical retrieval service. AB - INTRODUCTION: The Australian dust storm during the week of September 22, 2009, resulted in the grounding of a large portion of the air medical retrieval fleet in Queensland. We sought to determine whether during this event an increase occurred in cases requiring retrieval as a result of the dust storm, and whether the grounding of the retrieval fleet resulted in any adverse outcomes as a result of its inability to respond. METHODS: A retrospective review of respiratory and injury cases referred to the Queensland Emergency Medical System Coordination Centre from September 8 to October 5, 2009 was conducted. All cases with any respiratory or injury complaints were included. The number of cases, priority for retrieval, and the ability to retrieve these cases within the allocated time were examined and compared with those for a similar time frame in the previous year. RESULTS: A 62.5% increase in respiratory cases was seen, and 13.3% increase in injury cases during the week of the dust storm event, when compared with the previous year. Neither of these results reached statistical significance, but they demonstrate a practically important difference. For the month surrounding the dust storm event, a 48.5% (P = .04) increase in respiratory cases occurred, but no increase in injury cases when compared with the previous year. Only one urgent case was unable to be air medically retrieved during the study period as a result of grounding of the aircraft because of the dust storm event, but contingency arrangements were made for alternative transport. No adverse events were recorded during the study period. CONCLUSION: An increased demand on retrieval services was demonstrated during the period of the dust storm event. Despite grounding of the air medical fleet, all cases except one were able to be retrieved within clinically appropriate time frames or by alternative transport methods. Contingency plans need to be developed to cope with the possibility of similar events in the future, to prevent adverse events from occurring. PMID- 22055177 TI - Severity of cardiovascular disease patients transported by air ambulance. AB - INTRODUCTION: Although helicopters have been used in an air ambulance system for the past decade in Japan, the appropriate selection of patients for this transport mode has not been investigated. The present study investigates which patients could potentially benefit the most from helicopter emergency medical service (HEMS). METHODS: We investigated the extent of circulatory and respiratory support required in the intensive care unit (ICU) and ultimate outcomes of 2340 patients with cardiovascular disease admitted to 1 institution between October 2001 and December 2009. Two hundred and seventy were transported by HEMS (HEMS group), and 2070 were transported by other means (non-HEMS group). RESULTS: Temporary cardiac pacing, ventilator management, intra-aortic balloon pumping, percutaneous cardiopulmonary support, electrical defibrillation, and therapeutic hypothermia were more frequently required by patients in the HEMS group vs. the non-HEMS group (10.4%, 28.1%, 17.0%, 5.2%, 10.0% and 3.4% vs. 8%, 17.9%, 10.9%, 2.3%, 4.5% and 0.4%, respectively). The mortality rate was higher in the HEMS group than in the non-HEMS group in the ICU (9.6% vs. 5.3%). CONCLUSION: Disease was more clinically severe and the outcome was poorer among patients with cardiovascular diseases transported by HEMS than by other means. PMID- 22055178 TI - 2011 critical care transport workplace and salary survey. AB - Critical care transport (CCT) leaders from 260 organizations were invited to participate in an online, hosted survey of industry compensation and workplace practices. Approximately 150 questions were presented to participants, soliciting a broad base of information on CCT organizations, personnel, compensation, and workplace practices, notably alertness and fatigue management. CCT organizational salaries are represented by common job class and reported by summary with minimum, middle, and maximum hourly rates in a national aggregate and by Association of Air Medical Services region. PMID- 22055179 TI - ZFP57: KAPturing DNA methylation at imprinted loci. AB - In this issue of Molecular Cell, Quenneville et al. (2011) characterize the role of ZFP57 in the maintenance of DNA methylation at imprinting control regions (ICRs), revealing an allele-specific binding pattern, binding motif, and interactions with other epigenetic regulators. PMID- 22055180 TI - Unraveling a connection between DNA demethylation repair and cancer. AB - In this issue of Molecular Cell, Dango and Mosammaparast discover that the human oxidative demethylase ALKBH3 functions in complex with a DNA helicase to eliminate N3-methylcytosine lesions from ssDNA and that specific cancer cell lines are dependent on this activity for proliferation (Dango et al., 2011). PMID- 22055181 TI - Another "loophole" in miRNA processing. AB - In this issue of Molecular Cell, Suzuki et al. (2011) present the intriguing finding that an RNAse known to play an important role in immunity regulates miRNA processing in cancer and inflammation by cleaving the terminal loops of many miRNAs. PMID- 22055182 TI - Regulation of primary response genes. AB - Primary response genes (PRGs) are a set of genes that are induced in response to both cell-extrinsic and cell-intrinsic signals and do not require de novo protein synthesis for their expression. These "first responders" in the waves of transcription of signal-responsive genes play pivotal roles in a wide range of biological responses, including neuronal survival and plasticity, cardiac stress response, innate and adaptive immune responses, glucose metabolism, and oncogeneic transformation. Here we bring together recent advances and our current understanding of the signal-induced transcriptional and epigenetic regulation of PRGs. PMID- 22055183 TI - In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions. AB - The maintenance of H3K9 and DNA methylation at imprinting control regions (ICRs) during early embryogenesis is key to the regulation of imprinted genes. Here, we reveal that ZFP57, its cofactor KAP1, and associated effectors bind selectively to the H3K9me3-bearing, DNA-methylated allele of ICRs in ES cells. KAP1 deletion induces a loss of heterochromatin marks at ICRs, whereas deleting ZFP57 or DNMTs leads to ICR DNA demethylation. Accordingly, we find that ZFP57 and KAP1 associated with DNMTs and hemimethylated DNA-binding NP95. Finally, we identify the methylated TGCCGC hexanucleotide as the motif that is recognized by ZFP57 in all ICRs and in several tens of additional loci, several of which are at least ZFP57-dependently methylated in ES cells. These results significantly advance our understanding of imprinting and suggest a general mechanism for the protection of specific loci against the wave of DNA demethylation that affects the mammalian genome during early embryogenesis. PMID- 22055184 TI - DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation. AB - Demethylation by the AlkB dioxygenases represents an important mechanism for repair of N-alkylated nucleotides. However, little is known about their functions in mammalian cells. We report the purification of the ALKBH3 complex and demonstrate its association with the activating signal cointegrator complex (ASCC). ALKBH3 is overexpressed in various cancers, and both ALKBH3 and ASCC are important for alkylation damage resistance in these tumor cell lines. ASCC3, the largest subunit of ASCC, encodes a 3'-5' DNA helicase, whose activity is crucial for the generation of single-stranded DNA upon which ALKBH3 preferentially functions for dealkylation. In cell lines that are dependent on ALKBH3 and ASCC3 for alkylation damage resistance, loss of ALKBH3 or ASCC3 leads to increased 3 methylcytosine and reduced cell proliferation, which correlates with pH2A.X and 53BP1 foci formation. Our data provide a molecular mechanism by which ALKBH3 collaborates with ASCC to maintain genomic integrity in a cell-type specific manner. PMID- 22055185 TI - The structural basis for substrate recognition by mammalian polynucleotide kinase 3' phosphatase. AB - Mammalian polynucleotide kinase 3' phosphatase (PNK) plays a key role in the repair of DNA damage, functioning as part of both the nonhomologous end-joining (NHEJ) and base excision repair (BER) pathways. Through its two catalytic activities, PNK ensures that DNA termini are compatible with extension and ligation by either removing 3'-phosphates from, or by phosphorylating 5'-hydroxyl groups on, the ribose sugar of the DNA backbone. We have now determined crystal structures of murine PNK with DNA molecules bound to both of its active sites. The structure of ssDNA engaged with the 3'-phosphatase domain suggests a mechanism of substrate interaction that assists DNA end seeking. The structure of dsDNA bound to the 5'-kinase domain reveals a mechanism of DNA bending that facilitates recognition of DNA ends in the context of single-strand and double strand breaks and suggests a close functional cooperation in substrate recognition between the kinase and phosphatase active sites. PMID- 22055186 TI - Sub1 and RPA associate with RNA polymerase II at different stages of transcription. AB - Single-stranded DNA-binding proteins play many roles in nucleic acid metabolism, but their importance during transcription remains unclear. Quantitative proteomic analysis of RNA polymerase II (RNApII) preinitiation complexes (PICs) identified Sub1 and the replication protein A complex (RPA), both of which bind single stranded DNA (ssDNA). Sub1, homolog of mammalian coactivator PC4, exhibits strong genetic interactions with factors necessary for promoter melting. Sub1 localizes near the transcription bubble in vitro and binds to promoters in vivo dependent upon PIC assembly. In contrast, RPA localizes to transcribed regions of active genes, strongly correlated with transcribing RNApII but independently of replication. RFA1 interacts genetically with transcription elongation factor genes. Interestingly, RPA levels increase at active promoters in cells carrying a Sub1 deletion or ssDNA-binding mutant, suggesting competition for a common binding site. We propose that Sub1 and RPA interact with the nontemplate strand of RNApII complexes during initiation and elongation, respectively. PMID- 22055187 TI - SAGA and ATAC histone acetyl transferase complexes regulate distinct sets of genes and ATAC defines a class of p300-independent enhancers. AB - Histone acetyltransferase (HAT) complexes are coactivators that are important for transcriptional activation by modifying chromatin. Metazoan SAGA and ATAC are distinct multisubunits complexes that share the same catalytic HAT subunit (GCN5 or PCAF). Here, we show that these human HAT complexes are targeted to different genomic loci representing functionally distinct regulatory elements both at broadly expressed and tissue-specific genes. While SAGA can principally be found at promoters, ATAC is recruited to promoters and enhancers, yet only its enhancer binding is cell-type specific. Furthermore, we show that ATAC functions at a set of enhancers that are not bound by p300, revealing a class of enhancers not yet identified. These findings demonstrate important functional differences between SAGA and ATAC coactivator complexes at the level of the genome and define a role for the ATAC complex in the regulation of a set of enhancers. PMID- 22055188 TI - MCPIP1 ribonuclease antagonizes dicer and terminates microRNA biogenesis through precursor microRNA degradation. AB - MicroRNAs (miRNAs) are versatile regulators of gene expression and undergo complex maturation processes. However, the mechanism(s) stabilizing or reducing these small RNAs remains poorly understood. Here we identify mammalian immune regulator MCPIP1 (Zc3h12a) ribonuclease as a broad suppressor of miRNA activity and biogenesis, which counteracts Dicer, a central ribonuclease in miRNA processing. MCPIP1 suppresses miRNA biosynthesis via cleavage of the terminal loops of precursor miRNAs (pre-miRNAs). MCPIP1 also carries a vertebrate-specific oligomerization domain important for pre-miRNA recognition, indicating its recent evolution. Furthermore, we observed potential antagonism between MCPIP1 and Dicer function in human cancer and found a regulatory role of MCPIP1 in the signaling axis comprising miR-155 and its target c-Maf. These results collectively suggest that the balance between processing and destroying ribonucleases modulates miRNA biogenesis and potentially affects pathological miRNA dysregulation. The presence of this abortive processing machinery and diversity of MCPIP1-related genes may imply a dynamic evolutional transition of the RNA silencing system. PMID- 22055189 TI - Protein phosphatase 2A controls the order and dynamics of cell-cycle transitions. AB - Bistability of the Cdk1-Wee1-Cdc25 mitotic control network underlies the switch like transitions between interphase and mitosis. Here, we show by mathematical modeling and experiments in Xenopus egg extracts that protein phosphatase 2A (PP2A), which can dephosphorylate Cdk1 substrates, is essential for this bistability. PP2A inhibition in early interphase abolishes the switch-like response of the system to Cdk1 activity, promoting mitotic onset even with very low levels of Cyclin, Cdk1, and Cdc25, while simultaneously inhibiting DNA replication. Furthermore, even if replication has already initiated, it cannot continue in mitosis. Exclusivity of S and M phases does not depend on bistability only, since partial PP2A inhibition prevents replication without inducing mitotic onset. In these conditions, interphase-level mitotic kinases inhibit Cyclin E Cdk2 chromatin loading, blocking initiation complex formation. Therefore, by counteracting both Cdk1 activation and activity of mitotic kinases, PP2A ensures robust separation of S phase and mitosis and dynamic transitions between the two states. PMID- 22055190 TI - Atg8 transfer from Atg7 to Atg3: a distinctive E1-E2 architecture and mechanism in the autophagy pathway. AB - Atg7 is a noncanonical, homodimeric E1 enzyme that interacts with the noncanonical E2 enzyme, Atg3, to mediate conjugation of the ubiquitin-like protein (UBL) Atg8 during autophagy. Here we report that the unique N-terminal domain of Atg7 (Atg7(NTD)) recruits a unique "flexible region" from Atg3 (Atg3(FR)). The structure of an Atg7(NTD)-Atg3(FR) complex reveals hydrophobic residues from Atg3 engaging a conserved groove in Atg7, important for Atg8 conjugation. We also report the structure of the homodimeric Atg7 C-terminal domain, which is homologous to canonical E1s and bacterial antecedents. The structures, SAXS, and crosslinking data allow modeling of a full-length, dimeric (Atg7~Atg8-Atg3)(2) complex. The model and biochemical data provide a rationale for Atg7 dimerization: Atg8 is transferred in trans from the catalytic cysteine of one Atg7 protomer to Atg3 bound to the N-terminal domain of the opposite Atg7 protomer within the homodimer. The studies reveal a distinctive E1~UBL-E2 architecture for enzymes mediating autophagy. PMID- 22055191 TI - Structural basis of Atg8 activation by a homodimeric E1, Atg7. AB - E1 enzymes activate ubiquitin-like proteins and transfer them to cognate E2 enzymes. Atg7, a noncanonical E1, activates two ubiquitin-like proteins, Atg8 and Atg12, and plays a crucial role in autophagy. Here, we report crystal structures of full-length Atg7 and its C-terminal domain bound to Atg8 and MgATP, as well as a solution structure of Atg8 bound to the extreme C-terminal domain (ECTD) of Atg7. The unique N-terminal domain (NTD) of Atg7 is responsible for Atg3 (E2) binding, whereas its C-terminal domain is comprised of a homodimeric adenylation domain (AD) and ECTD. The structural and biochemical data demonstrate that Atg8 is initially recognized by the C-terminal tail of ECTD and is then transferred to an AD, where the Atg8 C terminus is attacked by the catalytic cysteine to form a thioester bond. Atg8 is then transferred via a trans mechanism to the Atg3 bound to the NTD of the opposite protomer within a dimer. PMID- 22055193 TI - ROS-mediated p53 induction of Lpin1 regulates fatty acid oxidation in response to nutritional stress. AB - The p53 protein is activated by stress signals and exhibits both protective and death-promoting functions that are considered important for its tumor suppressor function. Emerging evidence points toward an additional role for p53 in metabolism. Here, we identify Lpin1 as a p53-responsive gene that is induced in response to DNA damage and glucose deprivation. Lpin1 is essential for adipocyte development and fat metabolism, and mutation in this gene is responsible for the lypodystrophy phenotype in fld mice. We show that p53 and Lpin1 regulate fatty acid oxidation in mouse C2C12 myoblasts. p53 phosphorylation on Ser18 in response to low glucose is ROS and ATM dependent. Lpin1 expression in response to nutritional stress is controlled through the ROS-ATM-p53 pathway and is conserved in human cells. Lpin1 provides a critical link between p53 and metabolism that may be an important component in mediating the tumor suppressor function of p53. PMID- 22055192 TI - Oxygen-dependent cleavage of the p75 neurotrophin receptor triggers stabilization of HIF-1alpha. AB - Homeostatic control of oxygen availability allows cells to survive oxygen deprivation. Although the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha) is the main regulator of the hypoxic response, the upstream mechanisms required for its stabilization remain elusive. Here, we show that p75 neurotrophin receptor (p75(NTR)) undergoes hypoxia-induced gamma-secretase dependent cleavage to provide a positive feed-forward mechanism required for oxygen-dependent HIF-1alpha stabilization. The intracellular domain of p75(NTR) directly interacts with the evolutionarily conserved zinc finger domains of the E3 RING ubiquitin ligase Siah2 (seven in absentia homolog 2), which regulates HIF 1alpha degradation. p75(NTR) stabilizes Siah2 by decreasing its auto ubiquitination. Genetic loss of p75(NTR) dramatically decreases Siah2 abundance, HIF-1alpha stabilization, and induction of HIF-1alpha target genes in hypoxia. p75(NTR-/-) mice show reduced HIF-1alpha stabilization, vascular endothelial growth factor (VEGF) expression, and neoangiogenesis after retinal hypoxia. Thus, hypoxia-induced intramembrane proteolysis of p75(NTR) constitutes an apical oxygen-dependent mechanism to control the magnitude of the hypoxic response. PMID- 22055195 TI - Assessment of relative content of myoglobin, oxymyoglobin and metmyoglobin at the surface of beef. AB - A method of calculating the relative content of myoglobin, metmyoglobin and oxymyoglobin at the surface of beef is described. It is based on measurements of reflex attenuance of incident light at the isobestic points 572, 525, 473 and 730 nm. The latter value corresponds to the achromatic attenuance of light at the meat surface and can be used as an objective measure of its lightness. It was shown that the colour image of the meat surface, and the relative amounts of these three myoglobin derivatives, are influenced by the opacity of the surface layer. A variability in the light diffusing properties of the meat surface may be considered to be the primary factor in creating differences of colour perception of meat derived from animals of the same species and of the same approximate age. PMID- 22055194 TI - Autoantigen La promotes efficient RNAi, antiviral response, and transposon silencing by facilitating multiple-turnover RISC catalysis. AB - The effector of RNA interference (RNAi) is the RNA-induced silencing complex (RISC). C3PO promotes the activation of RISC by degrading the Argonaute2 (Ago2) nicked passenger strand of duplex siRNA. Active RISC is a multiple-turnover enzyme that uses the guide strand of siRNA to direct the Ago2-mediated sequence specific cleavage of complementary mRNA. How this effector step of RNAi is regulated is currently unknown. Here, we used the human Ago2 minimal RISC system to purify Sjogren's syndrome antigen B (SSB)/autoantigen La as an activator of the RISC-mediated mRNA cleavage activity. Our reconstitution studies showed that La could promote multiple-turnover RISC catalysis by facilitating the release of cleaved mRNA from RISC. Moreover, we demonstrated that La was required for efficient RNAi, antiviral defense, and transposon silencing in vivo. Taken together, the findings of C3PO and La reveal a general concept that regulatory factors are required to remove Ago2-cleaved products to assemble or restore active RISC. PMID- 22055196 TI - Changes in solubility and enzymic activity of muscle glycogen phosphorylase in PSE-muscles. AB - Comparison of the crude extracts of soluble proteins of PSE (pale, soft and exudative) and normal porcine muscles shows that the solubility and activity of muscle glycogen phosphorylase are diminished in PSE muscles. In the insoluble fractions of the muscle extract, however, an increased amount of a protein with the molecular weight of the phosphorylase subunit (92.500-95.000) can be found by means of SDS-electrophoresis. The PSE conditions with high temperatures of 36-40 degrees C in the first hour post mortem and a low pH of 5.3-5.8 at the same time post mortem are simulated with normal porcine muscles at twenty-four hours post mortem which causes the same change in solubility and activity of muscle glycogen phosphorylase as in PSE muscles. This proves, for the first time, that low pH and high temperature in whole muscles cause a denaturation of phosphorylase, as indicated by both reduced activity and decreased solubility. Previous studies have looked only at one of these aspects. This supports the hypothesis of Bendall & Wismer-Pedersen (1962) that in PSE muscles a partial denaturation of sarcoplasmic protein occurs. PMID- 22055197 TI - Measurement and prediction of tenderness in six beef muscles. AB - The relationship between subjective and objective evaluations of tenderness and that between the tenderness of different muscles in the same carcass have been examined in six beef muscles whose tenderness had been varied as a result of different post mortem treatments. Panel score (TP) was predicted by 'maximum force' (VF) and 'total work' (VW) on the Volodkevich bite tenderometer in both M. longissimus dorsi and M. semimembranosus (P < 0.001) and the regression coefficients were stable. In M. gluteus medius prediction was less significant (P < 0.01 for VF and P < 0.05 for VW) while in M. psoas major only VW was significant (P < 0.05). In M. biceps femoris and M. semitendinosus no significant prediction was found. These differences between muscles are attributed partly to varying changes in tenderness effected by post mortem treatments and partly to varying connective tissue content. The concept of one muscle acting as an index of toughness in a group of similar carcasses is thought to be untenable. PMID- 22055198 TI - M-line protein: Presence of two non-equivalent high molecular weight components. AB - M-line enriched protein preparations were prepared from glycerated rabbit muscle myofibrils by means of three alternate procedures and analysed with SDS polyacrylamide gel electrophoresis. A doublet corresponding to polypeptides with molecular weights of 193,000 and 182,000 was obtained in a ratio of2:3, respectively. The two bands are evident in SDS-gels of purified myofibrils, indicating that the proteins represent intrinsic M-line structural peptides. Transmission electron micrographs of the extracted myofibrils confirmed the effectiveness of the extraction procedures for removing M-line proteins. The possible significance of the M-line proteins to meat science is discussed. PMID- 22055199 TI - Prediction of water activity, a(w), in cook-soak equilibrated intermediate moisture meats. AB - The relationship between the moisture content and water activity, a(w), of several meat samples adjusted to intermediate moisture water activities by cook soak equilibration in glycerol solutions containing 9.5% sodium chloride was determined. Within experimental error the relationship was found to be unique for all the lean meats studied. It was also found that a modification of the Grover method (Grover, 1947) in which a(w) is determined from the well established relationship between a(w) and sucrose equivalent, E(s), was an excellent predictor of the final a(w) of the ssystem. E(s) was calculated from E(s) = E(1)X(1) + E(1)X(2) + ... etc. where E(1) are specific constants for each humectant and X(1) and X(2) are given as weight of humectant in the system/weight of water in the system. E values of 9.0 and 2.2 for sodium chloride and glycerol were applicable for initial salt concentrations of 0 to 20 (w/w)_and glycerol concentrations of 0 to 90% (w/w) The method was equally applicable to propylene glycol (E value 3.2)/salt systems and sorbitol (E value 1.0)/salt systems. PMID- 22055200 TI - Variation in the carcass characteristics of commercial British cattle. AB - Classification records for 1,150,000 beef carcasses, a one-third sampleof those classified by the Meat and Livestock Commission between 1973 and 1976, were used to examine the variation in weight, fatness and conformation of commercial British cattle. The overall ratio of male cattle (steers and young bulls) to heifers was 2.35 and young bulls comprised 4% of male cattle. There were only minor changes in the carcass characteristics over the three-year period considered. Mean carcass weights for steers (S), heifers (H) and young bulls (YB) were 264, 219 and 236 kg, respectively. Carcass subcutaneous fat percentages (SF(e)) were estimated from the distribution of carcasses between fat classifications. SF(e) for the three sexes were 8.21 (S), 8.81 (H) and 6.24 (YB). Regressions of SF(e) on carcass weight (kg) were 0.031 (S), 0.041 (H) and 0.026 (YB). There were important differences in the characteristics of carcasses from abbattoirs in different regions of the country. Carcass weights for steers ranged from 248 kg (northern England) to 280 kg (northern Scotland). Cattle slaughtered in northern Scotland were also fattest: SF(e) were 9.51 (S) and 10.2 (H). Using classification records, together with results from MLC dissection studies, national waste fat production in 1976 was estimated to be 48,000 t. PMID- 22055201 TI - Improved protein recovery from some meat industry by-products. AB - The proportion of protein recoverable from bovine heart, kidney, liver, lung, rumen and spleen by alkaline extraction, followed by reacidification, was found to be related to the temperature of extraction, the recovery of both lung and rumen protein at 60 degrees C being approximately twice that at 0 degrees C. Extraction for more than 2 h gave increases in protein recovery. The increased protein solubility was partly due to increased solubilisation of collagen and to a reduction in the quantity of protein precipitated by acidification. Alkaline extraction of lung and rumen at 60 degrees C resulted in the formation of the dipeptide lysinoalanine (0.39 and 0.49 g/16gN, respectively), with tracev amounts at 20 degrees C and 40 degrees C. The electrophoretic patterns of raw meat industry by-products are discussed in the light of previous findings. PMID- 22055202 TI - Blocking TREM-1 signaling prolongs survival of mice with Pseudomonas aeruginosa induced sepsis. AB - TREM-1 is a recently discovered receptor expressed on neutrophils and macrophages. Blocking of TREM-1 signaling improves the survival of mice with bacterial sepsis. However, the precise mechanism by which TREM-1 modulates the inflammatory responses is poorly defined. In this study, we investigated the role of TREM-1 in Pseudomonas aeruginosa-induced peritonitis. Our results showed that TREM-1 was not expressed on lymphocytes but emerged on the cell surface of neutrophils and peritoneal macrophages. Blockade of TREM-1 signaling significantly prolonged survival of mice with P. aeruginosa-induced peritonitis. However, blocking TREM-1 signaling had no effect on macrophage phagocytosis in vitro. Interestingly, the expression of the costimulatory molecules CD40 and CD86 on macrophages was significantly decreased after blocking TREM-1 signaling. Furthermore, interfering with TREM-1 engagement led to significant reduction of pro-inflammatory mediators such as IL-1, TNF-alpha, MCP-1 and IFN-gamma. Therefore, our results showed that TREM-1 could be a potential therapeutic target for bacterial sepsis. PMID- 22055203 TI - Evaluation of new chalcone derivatives as polyphenol oxidase inhibitors. AB - A newly series of 4-(phenylurenyl)chalcone (4a-j) and 4' (phenylurenyl/thiourenyl)chalcone (9a-l) derivatives were synthesized and their inhibitory effects on the diphenolase activity of banana tyrosinase were evaluated. Tyrosinase has been purified from banana on an affinity gel comprised of Sepharose 4B-l-tyrosine-p-aminobenzoic acid. The result showed that 4a-j inhibited the PPO enzyme activity. Conversely, 9a-h and 9i-l showed activator effect on tyrosinase enzyme activity. PMID- 22055204 TI - Synthesis and antileishmanial evaluation of 1-aryl-4-(4,5-dihydro-1H-imidazol-2 yl)-1H-pyrazole derivatives. AB - A series of 1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (4a-g) and 5 amino-1-aryl-4-(4,5-dihydro-1H-imidazol-2-yl)-1H-pyrazoles (5a-g) were synthesized and evaluated in vitro against three Leishmania species: L. amazonensis, L. braziliensis and L. infantum (L. chagasi syn.). The cytotoxicity was assessed. Among the derivatives examined, six compounds emerged as the most active on promastigotes forms of L. amazonensis with IC(50) values ranging from 15 to 60 MUM. The reference drug pentamidine presented IC(50)=10 MUM. However, these new compounds were less cytotoxic than pentamidine. Based on these results, the more promising derivative 5d was tested further in vivo. This compound showed inhibition of the progression of cutaneous lesions in CBA mice infected with L. amazonensis relative to an untreated control. PMID- 22055205 TI - Diphenyl diselenide in vitro and in vivo activity against the oomycete Pythium insidiosum. AB - This study evaluated the in vitro activity of diphenyl diselenide against 19 Pythium insidiosum isolates and the in vivo therapeutic response of rabbits with experimentally induced pythiosis. In vitro: susceptibility tests were performed using the broth macrodilution method in accordance with the CLSI document M38-A2. The criteria for interpretation were as follows: MIC-1 and MIC-2 (inhibition of 90% and 100% of mycelium growth, respectively) and the minimum fungicide concentration (MIC-3). In vivo: twenty rabbits were divided into four groups with five animals each and treated for 40 consecutive days: groups 1 and 2 (experimentally induced pythiosis) were treated with diphenyl diselenide (10mg/kg/day) and canola oil (1 mL/kg/day), respectively; groups 3 and 4 (controls) were treated with canola oil (1 mL/kg/day) and diphenyl diselenide (10mg/kg/day), respectively. Toxicity was evaluated using biochemical and haematological parameters. In vitro susceptibility tests showed that 89.4% of isolates had a MIC-1 <= 0.5 MUg/mL, 84.2% of isolates had a MIC-2 <= 1.0 MUg/mL and 94.7% of isolates had a MIC-3 <= 2.0 MUg/mL. The in vivo assay suggested that this compound has a fungistatic activity, and the biochemical and haematological parameters indicated that there was no renal, hepatic or haematological toxicity. The comparison of the unsaturated iron binding capacity levels between animals with and without pythiosis suggested the involvement of iron metabolism in the pathogenesis of pythiosis. This study demonstrated the absence of detectable toxicity caused by diphenyl diselenide and the in vitro fungicidal and in vivo fungistatic activities of this drug, which makes it an option for future therapeutic approaches in the treatment of pythiosis. PMID- 22055206 TI - The role of toll-like receptors in the pathogenesis of Streptococcus suis. AB - Streptococcus suis is an important agent of swine and human meningitis. Sequence type (ST) 7 emerged in China and was responsible for the human epidemic caused by S. suis in 2005. The virulence of S. suis ST7 is greater than the wild type pathogenic S. suis, ST1; however, the mechanisms for this increased pathogenicity are unknown. The aim of this study was to determine the role of different toll like receptors (TLRs) involved in regulating the host response to the S. suis infection and to speculate on differing mechanisms used by ST7 strains to induce disease. Here we compared two ST7 strains isolated in the 2005 Sichuan outbreak to two ST1 strains. Our data show TLR2, 6 and 9 are involved in the recognition of heat-killed S. suis independent of the ST type. We found the TLR-dependent cytokine production differed between the two types of strains using whole cell lysate proteins. TLR6 played a greater role in cytokine production induced by the whole cell lysate proteins from the ST7 strain than in that induced by the ST1 strain lysates. The data suggest that mechanisms of inflammation induced by S. suis strains differ where this will be useful in designing efficient strategies in combating streptococcal toxic shock-like syndrome caused by the S. suis ST7 strains. PMID- 22055207 TI - School racial composition and race/ethnic differences in early adulthood health. AB - We investigate whether school racial composition is associated with racial and ethnic differences in early adult health. We then examine whether perceived discrimination, social connectedness, and parent support attenuates this relationship. Using U.S. data from Waves I and IV of the National Longitudinal Survey of Adolescent Health, we found that black adolescents attending predominantly white schools reported poorer adult health while Asians reported better health. Further research is warranted to understand whether there are qualitative differences in the treatment of racial and ethnic minorities within certain school contexts and how that differential treatment is related to adult health outcomes. PMID- 22055208 TI - Impact of a multidisciplinary intervention on antibiotic use for nursing home acquired pneumonia. AB - BACKGROUND: Academic detailing in nursing homes (NHs) has been shown to improve drug use patterns and adherence to guidelines. OBJECTIVE: The purpose of this study was to evaluate the impact of a multidisciplinary intervention that included academic detailing on adherence to national nursing home-acquired pneumonia (NHAP) guidelines related to use of antibiotics. METHODS: This quasi experimental study evaluated the effects of a 2-year multifaceted and multidisciplinary intervention targeting implementation of national evidence based guidelines for NHAP. Interventions took place in 8 NHs in Colorado; 8 NHs in Kansas and Missouri served as controls. Interventions included (1) educational sessions for nurses to improve recognition and timely treatment of NHAP symptoms and (2) academic detailing to clinicians by pharmacists regarding diagnostic and prescribing practices. Differences in antibiotic use between groups were compared after 2 intervention years relative to baseline. RESULTS: A total of 549 episodes of NHAP were evaluated in the intervention group and 574 in the control group. Compared with baseline, 1 facility in the intervention group significantly improved in guideline adherence for optimal antibiotic use (P = 0.007), whereas no facilities in the control group improved. The mean adherence score for optimal antibiotic use in intervention NHs increased from 60% to 66%, whereas the control NHs increased from 32% to 39% (P = 0.3). Mean adherence to guidelines recommending antibiotic use within 4 hours of NHAP diagnosis increased from 57% to 75% in intervention NHs but decreased from 38% to 31% in control NHs (P = 0.0003 for difference). There was no difference between intervention and control NHs for guideline adherence regarding optimal duration of antibiotic use. CONCLUSIONS: The ability of this multifaceted study to repeatedly remind nursing staff of the importance of timely antibiotic administration contrasts with its limited academic detailing interaction with clinicians. This difference within the intervention may explain the differential impact of the intervention on antibiotic guideline adherence. PMID- 22055209 TI - Development and testing of a tool for assessing and resolving medication-related problems in older adults in an ambulatory care setting: the individualized medication assessment and planning (iMAP) tool. AB - BACKGROUND: Medication is one of the most important interventions for improving the health of older adults, yet it has great potential for causing harm. Clinical pharmacists are well positioned to engage in medication assessment and planning. The Individualized Medication Assessment and Planning (iMAP) tool was developed to aid clinical pharmacists in documenting medication-related problems (MRPs) and associated recommendations. OBJECTIVE: The purpose of our study was to assess the reliability and usability of the iMAP tool in classifying MRPs and associated recommendations in older adults in the ambulatory care setting. METHODS: Three cases, representative of older adults seen in an outpatient setting, were developed. Pilot testing was conducted and a "gold standard" key developed. Eight eligible pharmacists consented to participate in the study. They were instructed to read each case, make an assessment of MRPs, formulate a plan, and document the information using the iMAP tool. Inter-rater reliability was assessed for each case, comparing the pharmacists' identified MRPs and recommendations to the gold standard. Consistency of categorization across reviewers was assessed using the kappa statistic or percent agreement. RESULTS: The mean kappa across the 8 pharmacists in classifying MRPs compared with the gold standard was 0.74 (range, 0.54-1.00) for case 1 and 0.68 (range, 0.36-1.00) for case 2, indicating substantial agreement. For case 3, percent agreement was 63% (range, 40%-100%). The mean kappa across the 8 pharmacists when classifying recommendations compared with the gold standard was 0.87 (range, 0.58-1.00) for case 1 and 0.88 (range, 0.75-1.00) for case 2, indicating almost perfect agreement. For case 3, percent agreement was 68% (range, 40%-100%). Clinical pharmacists found the iMAP tool easy to use. CONCLUSIONS: The iMAP tool provides a reliable and standardized approach for clinical pharmacists to use in the ambulatory care setting to classify MRPs and associated recommendations. Future studies will explore the predictive validity of the tool on clinical outcomes such as health care utilization. PMID- 22055210 TI - Comparison of the efficacy and tolerability profile of liraglutide, a once-daily human GLP-1 analog, in patients with type 2 diabetes >=65 and <65 years of age: a pooled analysis from phase III studies. AB - BACKGROUND: Managing elderly patients with type 2 diabetes poses particular challenges, so it is important to evaluate the efficacy and tolerability profile of antidiabetic therapies specifically in this patient population. OBJECTIVE: The aim of our study was to compare the efficacy and tolerability profile of liraglutide, a GLP-1 analog, in elderly (>=65 years) and younger (<65 years) patients with type 2 diabetes. METHODS: A pooled analysis of 6 randomized, placebo-controlled, multinational trials included data from 3967 patients aged18 to 80 years with type 2 diabetes and glycosylated hemoglobin (HbA(1c)) of 7% to 11%. Of these, 552 patients >=65 years received liraglutide 1.8 mg, liraglutide 1.2 mg, or placebo; 2231 patients <65 years received liraglutide 1.8 mg, liraglutide 1.2 mg, or placebo for 26 weeks. End points were: change in HbA(1c), fasting plasma glucose, body weight, and blood pressure: as marked to identify elements tracked for change from baseline; hypoglycemic episodes; and adverse events. RESULTS: Reduction in HbA(1c) from baseline was significantly greater with liraglutide 1.8 mg versus placebo (least squares mean difference: >=65 years, 0.91% [95% CI, 0.69-1.12]; <65 years, 1.17% [95% CI, 1.06-1.28]; both, P < 0.0001) and with liraglutide 1.2 mg versus placebo (>=65 years, 0.87% [95% CI, 0.64-1.11]; <65 years, 1.10% [95% CI, 0.98-1.22]; both, P < 0.0001). For fasting plasma glucose, comparable results were observed between liraglutide 1.8 mg or 1.2 mg and placebo for both age groups (P < 0.0001). No statistically significant difference in body weight change was seen with liraglutide between the age groups. The proportion of patients reporting minor hypoglycemia was low and appeared comparable between the >=65-year-old (4.3%-15.2%) and <65-year-old (8% 13.2%) groups. Likewise, adverse events appeared comparable in nature and frequency. CONCLUSION: Liraglutide provides effective glycemic control and is well tolerated in patients >=65 and <65 years of age with type 2 diabetes. These data suggest that liraglutide may be a suitable treatment option for older patients who may have additional age-related complications. PMID- 22055211 TI - Flow cytometry enables identification of sporophytic eliciting stress treatments in gametic cells. AB - Flow cytometry was used to quantify the effect of individual and combined stress treatments on elicitation of androgenesis by analyzing the relative nuclear DNA content of in vitro cultured microspores of Pisum sativum L. Differences in relative nuclear DNA content of microspores within anthers after stress treatments were clearly evident from the flow cytometry profiles, and permitted us to predict whether a combination of stresses were elicitors or enhancers of androgenesis. This is the first report to assess the effect of various stress treatments in a plant species based on relative nuclear DNA content and to use this information to categorize them as 'elicitors' or 'enhancers'. Flow cytometry represents a simple, quick and reliable way to analyze and discriminate the effect of various stress treatments on elicitation of androgenesis. These results form a solid basis for further efforts designed to enhance responses and to extend double haploid technology to other legumes. PMID- 22055212 TI - Changes in growth irradiance are reflected on H+ATPase activity of plasma membrane enriched vesicles from maize (Zea mays L.) roots. AB - Leaves change their photosynthetic activity in response to growth light conditions, but little is known about what may happen at the root level. The effect of irradiance level (high or low) on transport activities of root plasma membrane enriched vesicles was studied in maize (Zea mays L.) plants. High irradiance appears to have a differential promoting effect on proton transport activity and ATPase activity, the most pronounced one on ATP-dependent H(+) accumulation. Furthermore, our results put in evidence a correlation between increase in enzyme activity and increase in MHA2 gene transcription level. Finally, high irradiance results in increased uptake rates of nitrate and in a higher reduction rate of the anion. We suggest that high light-induced changes in plasma membrane H(+)ATPase activity and transcription might have an adaptive role in sustaining the higher request for the nitrate resulting from increased photosynthate availability. PMID- 22055213 TI - [The social cost of depression in the city of Sabadell (Barcelona, Spain) (2007 2008)]. AB - OBJECTIVE: To determine the social cost and burden of depression in the city of Sabadell (Barcelona, Spain) in 2007 and 2008. METHOD: The social cost of depression was calculated using the prevalence approach, based on information obtained in the development of the European Project Against Depression (EAAD). The results referred to the cost of public resources used, and the sources came from the appropriate official registers. RESULTS: The direct public cost of depression in the city of Sabadell was ? 9,155,620 in 2007 and ? 9,304,706 in 2008. The relative weight of primary care visits and the use of drugs accounted for more than 85% of direct costs. In the section of indirect costs, the cost of permanent work disability could not be obtained. Indirect costs amounted to ? 9,720,225 in 2007 and ? 9,763,541 in 2008. In both years, the highest weight corresponded to temporary work disability reaching ? 8,561,962 and ? 7,333,181, respectively. CONCLUSIONS: Depression has a substantial economic impact on the health system because it is associated with high direct public costs. However, the lack of knowledge of the cost associated with permanent work disability is a major limitation, as this cost category represents the highest percentage for this disorder. PMID- 22055214 TI - [Family and community medicine and the university. SESPAS report 2010]. AB - Family and community medicine is an academic subject, a medical specialty and a health profession with distinct dimensions: healthcare, teaching, research and management. In this discipline, the object of knowledge is the person, understood as a whole. Family medicine, as an academic subject, and primary care, as a health education setting, should be incorporated into the core graduate and postgraduate curricula. The absence of these elements leads to training bias and has major repercussions on quality, coordination and patient safety. The development of the Health Professions Act and the construction of the European Higher Education Area (EHEA) have created a favorable climate for the presence of this discipline in the university. Since the 1960s, family medicine has been consolidated as an academic subject with its own departments in almost all European universities, and a significant number of family physicians are teachers. A balance has been achieved between the hospital-based system (based on theory, disease, and the biological model) and the patient-centred model (based on problem solving, community-oriented and the bio-psycho-social model). The introduction of family and community medicine as a specific subject, and as a transverse subject and as an option in practicals, represents the adaptation of the educational system to social needs. This adaptation also represents a convergence with other European countries and the various legal requirements protecting this convergence. However, this new situation requires a new structure (departments) and faculty (professors and associate and assistant professors). PMID- 22055215 TI - The effect of sex condition and growth implants on bovine muscle fiber characteristics. AB - Steers, bulls and bulls implanted with Synovex-S or Ralgro were slaughtered at 12 and 16 months of age. With increasing animal age, the percentage of intermediate fibers decreased while the percentage of white fibers increased. The area of all fibers increased with increasing age. Bulls had a higher percentage of red fibers, larger red and intermediate fibers and a higher percentage area of red and intermediate fibers compared with steers. Implanted bulls were generally intermediate to intact bulls and steers in muscle fiber type characteristics. Carcass fat measurements and tenderness ratings were positively correlated to the percentage of white muscle fibers and negatively correlated to the percentage of intermediate fibers. Carcass characteristics and sensory properties of meat are discussed in relation to muscle fiber characteristics. PMID- 22055216 TI - Post-mortem spectrophotometry of pork and beef using quartz optical fibres. AB - A high intensity xenon illuminator, a diffraction grating monochromator and a photomultiplier were linked to pork or beef samples with a bifurcated light guide composed of quartz optical fibers in a random pattern. When muscle fibres and optical fibres were parallel and coaxial, absorbance was greater than when they were perpendicular. As judged by the coefficient of variation at different wavelengths, the effect of fat in the measuring field was not uniform at all wavelengths. For the study of optical changes in pork, from slaughter to 24 h, the fibre-optic probe was maintained in a stationary position. The changes detected were: (1) a slight transient increase in absorbance at all wavelengths in the first few hours post mortem, (2) an eventual decline in absorbance at all wavelengths to reach minimum values at 24 h and (3) a spectrally limited decrease in absorbance, peaking somewhere in the 390 to 450 nm range, which started immediately post mortem. PMID- 22055217 TI - National estimates of the body composition of British cattle, sheep and pigs with special reference to trends in fatness. A review. PMID- 22055218 TI - National estimates of the body composition of British cattle, sheep and pigs with special reference to trends in fatness. A review. AB - National carcass classification records for cattle, sheep and pigs were used as a basis for estimating the body composition of British livestock slaughter populations. The tissue percentages of carcasses in each classification fatness range were estimated from regression equations constructed using data from breed comparison trials and other sources. The lipid and protein contents of the tissues were then estimated using regression equations from body composition studies. The mean carcass composition, and lean and fat production from current populations (1984) were compared with those of ten years ago. There has been an important increase of 20 kg (8%) in carcass weight for beef but no change in carcass composition. The average beef carcass in 1984 was estimated to contain 23% lipid (inclusive of lipid in perinephric and retroperitoneal fat). The weight of sheep carcasses has fallen by 0.6 kg (3 1 2% ) since 1977 without any appreciable change in carcass composition. The average sheep carcass in 1984 was estimated to contain 24% lipid. The lipid content of the average pig carcass was estimated to have fallen significantly from 27% in 1975 to 22% in 1984, with a small increase in carcass weight. PMID- 22055219 TI - The bacteriological quality, fat and collagen content of minced beef at retail level. AB - Samples of minced (ground) beef were purchased on three occasions from seven supermarkets and eleven butcher's shops in one geographical area during winter. Total viable counts (at 37 degrees C and 20 degrees C), numbers of Enterobacteriaceae (at 37 degrees C) and Escherichia coli biotype I were similar between shop type. No Salmonella spp. were detected. In general, bacterial counts were lower than in a similar survey four years previously. The fat and collagen content of the samples was also determined. In a previous survey, 37% of samples contained more than 25% fat, while, in this survey, only 17% of the samples exceeded that level. Collagen levels in the mince at retail ranged from 1.4% to 4.4% (1.5% to 5.1% on a wet fat-free basis). PMID- 22055220 TI - Heat-induced changes in the proportion of types I and III collagen in bovine Longissimus dorsi. AB - Intramuscular collagen (IMC) was isolated from the Longissimus dorsi of six Simmental bulls, 17 months of age, to evaluate the effect of heating on the proportion of types I and III collagen. Cyanogen bromide (CNBr) peptides were prepared from unheated IMC and the soluble and insoluble fractions of IMC heated to 70 degrees C for 70 min or 90 degrees C for 140 min. Percentage of type III collagen was determined by densitometric scans of the CNBr peptides, alphal(I)CB8 and alphal(III)CB8, as resolved by SDS-PAGE. Percentage of collagen solubilized was greater (P < 0.05) at 90 degrees C than at 70 degrees C. The 70 degrees C and 90 degrees C insoluble IMCs were similar (P > 0.05) for percentage of type III, but both had a greater (P < 0.05) percentage of type III than unheated IMC, indicating that type I is more heat labile than type III. Heat-soluble IMC contained both alpha and beta components and the CNBr peptides of 70 degrees C soluble IMC were mostly type I. These results indicated that heating intramuscular collagen from bulls mainly solubilized type I collagen. Improved tenderness associated with increased heat solubility of collagen may be more closely related to heat-induced solubilization of type I than of type III collagen. PMID- 22055222 TI - Factors influencing frozen display life of lamb chops and steaks: Effect of packaging and temperature. AB - Frozen lamb loin and rib chops and leg steaks were wrapped in film of high oxygen permeability or vacuum packaged in film of low oxygen permeability and stored in the dark at -10, -20 or -35 degrees C for periods from 0-20 weeks. After storage, the wrapped cuts were displayed in an open-top cabinet operating at -20 degrees C under continuous fluorescent lighting (Philips Deluxe 32 degrees ). Cuts were evaluated by a trained colour panel to determine acceptable display life, and chop lean colour was evaluated using a Hunter colorimeter. Cuts wrapped in oxygen permeable film had better colour retention during storage and display. Storage of the frozen chops reduced the display life, with the largest effect occurring during the first 4-5 weeks' storage. Cuts stored at -10 degrees C had no display life after 10 weeks' storage, whereas cuts stored at -20 and -35 degrees C had some acceptable display life even after the longest storage period tested. Rib chops in general had better colour stability than loin chops. PMID- 22055223 TI - Effect of dietary Vitamin E on the stability of raw and cooked pork. AB - Experiments were designed to investigate the effects of dietary alpha-tocopherol supplementation for 2 weeks prior to slaughter on plasma and muscle alpha tocopherol levels and on the oxidative stability of raw and cooked pig muscle during refrigerated storage at 4 degrees C. Plasma and muscle alpha-tocopherol levels of the pigs on the alpha-tocopherol supplemented diet (200 mg alpha tocopherol acetate/kg feed) were ~2.5-fold higher than those of the pigs on the control diet (30 mg alpha-tocopherol acetate/kg feed). Dietary supplementation with alpha-tocopherol significantly (p < 0.01) improved the oxidative stability of both raw and cooked muscle after storage at 4 degrees C for up to 8 days. alpha-Tocopherol stabilized the membrane-bound lipids against metmyoglobin/H(2)O(2)-initiated oxidation and also significantly (p < 0.05) improved the oxidative stability of rendered fat. PMID- 22055224 TI - Preparation and storage stability of dried salted mutton. AB - Minced (8 or 18 mm plate) mutton with salt (25%) and sorbate (0.4%) was pressed into cakes about 11 cm in diameter and 3 cm high. The cakes were partially dried in an air oven at 40 degrees C for 48 h to a water activity of about 0.75. The cakes were packed, either in vacuo or in air, and stored at 30 or 2 degrees C for up to 60 days. Objective assessment of quality showed that these dried salted meats can be kept for up to 60 days at 30 degrees C with little loss of textural or nutritional quality although some fading, due to haemoprotein breakdown, occurs. Packaging in vacuum, however, minimises this loss of colour and would be recommended for centralised manufacture prior to distribution in developing, tropical countries. PMID- 22055221 TI - Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation. AB - Monogenic hereditary diseases, such as haemophilia A and B, are ideal targets for gene therapeutic approaches. While these diseases can be treated with protein therapeutics, such as factor VIII (FVIII) or IX (FIX), the notion that permanent transfer of the genes encoding these factors can cure haemophilia is very attractive. An underlying problem with a gene therapy approach, however, is the patient's immune response to the therapeutic protein (as well as to the transmission vector), leading to the formation of inhibitory antibodies. Even more daunting is reversing an existing immune response in patients with pre existing inhibitors. In this review, we will describe the laboratory and clinical progress, and the challenges met thus far, in achieving the goal of gene therapy efficacy, with a focus on the goal of tolerance induction. PMID- 22055225 TI - Species identification of cooked meats by DNA hybridization assay. AB - Dot-blots hybridization technique has been applied to the detection of species specific DNA fragments in the cooked meats of chicken, pig, goat, sheep, and beef. The samples were obtained from the meats which were heated for 30 min at 80, 100 or 120 degrees C. The probes, biotin-labeled chromosomal DNA fragments, were hybridized to the sample DNA on nylon membranes. The species of the meats cooked at 100 or 120 degrees C were identified at 100 ng/dot of the sample DNA. The probes for chicken and pig did not show cross-reactivity, but those for the ruminants reacted with other ruminant DNA. Using this method, chicken, pig and beef were detected from 50 mg of the commercial canned products. PMID- 22055226 TI - An assessment of the role of pH differences in determining the relative tenderness of meat from bulls and steers. AB - Samples of M. longissimus dorsi from 16-20 month Friesian bulls or steers (80/group) were assessed for a range of meat quality characteristics after being held at ambient temperature for 24h (to avoid cold-shortening) and then at 0-2 degrees C for 6 days. Mean ultimate pH was significantly higher for samples from the bulls (6.35 versus 5.89), and as a consequence, reflectance values were lower, sarcomere lengths were shorter, and expressed juice and cooking losses were lower. Mean Warner-Bratzler shear values did not differ between the groups, apparently because the bull values were mainly above the peak of the pH/shear force curve, while the steer values were mainly below it. There was no evidence that the relationship between shear force and pH differed for samples from the bulls and steers. Results suggested that the increased shear force with increased pH up to 6.2 was at least partly due to a decreased sarcomere length. It is suggested that some of the differences in tenderness between beef from bulls and steers, that have been reported elsewhere, may have been largely due to differences in ultimate pH values. PMID- 22055227 TI - The effects of conditioning on meat collagen: Part 4-The use of pre-rigor lactic acid injection to accelerate conditioning in bovine meat. AB - Injection of fresh bovine muscle with 0.1 m lactic acid (to a level of 10% of original muscle weight) resulted in a pH decline to a minimum pH of 5.33 at 15 degrees C only 3 h after injection. Untreated muscle reached the same pH after 26 h when held at the same temperature. Fresh, unconditioned meat colour was unaffected by pre-rigor 0.1 m lactic acid injection as assessed by visual inspection. The percentage of perimysial collagen extracted as the soluble form was significantly higher (P < 0.05) from three muscles of varying quality when pre-injected with 0.1 m lactic acid and conditioned from 1 to 14 days, than from conditioned untreated muscles. SDS-polyacrylamide gel electrophoresis of CNBr peptides from insoluble perimysium obtained from three muscles of varying quality revealed no obvious differences due to pre-rigor lactic acid injection before conditioning. However, analysis of the high molecular weight perimysial collagen CNBr peptides from lactic acid treated muscles by two-dimensional SDS polyacrylamide gel electrophoresis revealed an increased incidence of degradation in this region compared with untreated controls. These data strongly suggest that pre-rigor injection of beef muscle with lactic acid may accelerate conditioning. The implications of this finding are discussed. PMID- 22055228 TI - Metmyoglobin reductase activity in bovine muscles. AB - Cow muscles (Longissimus dorsi, Tensor fasciae latae, Psoas major, Diaphragma medialis), with different colour stabilities, were used to measure 'Metmyoglobin reductase activity' in different conditions. The effects of pH and temperature on in vitro metmyoglobin reduction were analysed. The highest metmyoglobin reductase activity was localized in microsomes and in more or less intact mitochondria by means of differential centrifugations. The most unstable muscles, from the colour point of view, presented the highest reducing activities and no differences were noted between activities measured in aerobic or anaerobic conditions. PMID- 22055229 TI - Effect of water and salt content on protein solubility and water retention of meat preblends. AB - Different preblend water contents at a constant ionic strength were investigated to determine if increasing water availability would increase protein solubility and water retention in meat preblends. Four salt levels (0, 2, 4 and 8%) and four water levels (0, 20, 40 and 80% formulation water) were used with ground bovine semimembranosus muscle that had been frozen once. Ground muscle was mixed with either NaCl alone (0% formulation water) or NaCl and brine (20, 40 and 80% formulation water) for the 2, 4 and 8% NaCl treatments. Distilled water was used for the 0% NaCl treatment. The mixtures were stored at 5 degrees C for 12 h. Following storage, the water/brine content was standardized, and protein solubility and water retention were measured. Elevating the water content of preblends, in which the salt concentration had been standardized, increased the water retained during centrifugation (P < 0.05). Although not statistically significant, a similar trend was observed for protein solubility. Four percent NaCl produced the greatest protein dissolution and water retention. PMID- 22055230 TI - Effect of post-mortem time and temperature on bovine intramuscular collagen. AB - A section of longissimus muscle was excised from six steers within 1 h post mortem. Half of the muscle section from each animal was held at 37 degrees C (HT) and the other half was maintained at 1 degrees C (C). Samples were collected from each muscle section in each treatment at 12 and 24 h to study the effect of conditioning temperature and incubation time on collagen properties by comparing the per cent soluble collagen and the relative distribution of collagen components. More of each collagen component (alpha(1), alpha(2), beta(11) and beta(12)) was present on SDS gels of samples incubated for 24 h versus 12 h. Although the collagen solubility did not increase to a great extent in the HT conditioned samples when compared with C samples, the HT treatment increased the effect of post-mortem ageing (i.e. more collagen molecules were solubilised and entered the gel during electrophoresis). Each collagen component, expressed as a percentage of total collagen, remained relatively constant when comparing different temperatures or post-mortem times. This indicates that the increase in collagen components being absorbed on the gels of 24 h post-mortem samples is mainly caused by an increase in the release of total collagen from the connective tissue matrix and not by the specific release of any one component. It was also found that some breakage of collagen crosslinks occurred during high temperature conditioning. No change in type III collagen of intramuscular connective tissue was found in this study. PMID- 22055231 TI - Pressure-induced pH and length changes in muscle. AB - The response to increase in pressure of pre- and post-rigor muscle strips supporting a load has been investigated by measuring length changes with application of pressure up to 150 MPa in a windowed pressure vessel. The response of the pre-rigor strips depended on temperature; at 30 degrees C the strips contracted, then, after some minutes, lengthened, presumably because of a breakdown of myofibrillar integrity. At 0 degrees C the cold-shortened muscle lengthened but if pressure was released the strips shortened again. Loaded post rigor muscle strips lengthened with application of pressure. It is suggested that the conditions that prevail in pre-rigor muscle are not as favourable for disaggregation of the myofilaments as those in post-rigor muscle. Measuresurement of pH changes in pre-rigor pressure-treated muscle showed these were accelerated at 30 degrees C, but completely inhibited by treatment at 0 degrees C for 3 or 24h. PMID- 22055232 TI - Improvement of meat quality in pigs by beta-adrenergic blockade. AB - The value of giving pigs the beta-adrenergic blocking drug carazolol preslaughter to improve meat quality was tested in a stress-resistant breed (Large White) and a stress-susceptible breed (Pietrain). Pigs averaging about 70kg liveweight were injected intramuscularly (1 mg per 100 kg liveweight) 0.5h before being transported to the slaughterhouse. The journey lasted 4 h and covered about 150 km and the pigs were slaughtered after 1 h in lairage. Treatment with carazolol reduced the incidence of PSE meat and considerably improved meat quality in the stress-susceptible Pietrain breed but had little effect in the stress-resistant Large Whites which produced good meat quality in both control and treated groups. PMID- 22055233 TI - Myofibrils of cooked meat are a continuum of gap filaments. AB - When cooked meat is subjected to high degrees of stretch it becomes apparent in high magnification electron micrographs that A-filaments have ceased to exist. The A-band is filled with a coagulum of actomyosin. Fragmentation of this coagulum during stretch reveals an array of fine filaments (identified as gap filaments). This result is obtained irrespective of rigor temperature, state of contraction or degree of cooking. If the meat is first aged, the gap filaments surviving in the I-band are too weak to open up the A-band. The results show that myofibrils in cooked meat are entirely dependent on heat-stable gap filaments for structural continuity and tensile strength. Theories of meat tenderness must be revised accordingly. PMID- 22055234 TI - Effect of electrical stunning methods on petechial haemorrhages and on the blood pressure of lambs. AB - Electrical stunning of lambs to render them unconscious and insensible to pain can result in blood splash (spots of blood in muscles) or speckle (petechial haemorrhages in fat or connective tissue overlying the muscle). Stunning through electrodes applied to the head causes mainly blood splash with some speckle, while currents applied head-to-back or head-to-foreleg can produce speckle without blood splash. To identify the causes of speckle, animal movement and blood pressure changes that occur during stunning were measured. Three different stunning methods were employed: head-only, head-to-back and head-to-foreleg. Head only stunning, which does not stop the heart and produces a moderate amount of speckling, was accompanied by elevated arterial blood pressures up to 300 mm Hg, and venous pressures up to 100 mm Hg. The carcass became rigid on stunning but reflex kicking occurred when the hind legs were shackled. Head-to-back stunning, which stops the heart, produced a momentary arterial and venous blood pressure rise during the stun, as a result of thoracic pressure changes, followed by a decline in pressure to 40-50 mm Hg. The muscles became markedly rigid due to direct stimulation of the loin and spontaneous kicking was absent following current switch off, although spontaneous coughing persisted. Stillness associated with head-to-back stunning was accompanied by the highest incidence and severity of speckling, whereas head-to-foreleg stunning, which also stops the heart, resulted in less muscle contraction and was accompanied by the least incidence and severity of speckling. Kicking was also eliminated if sufficiently high currents were used. Stopping the heart with KCl before a head-to-back stun lowered arterial blood pressure to 20-30 mm Hg and markedly reduced speckle. Abolition of nervously mediated muscle movement with curare before stunning resulted in no observable speckle in head-only stunned lambs but, in the head-to back stunned lambs, there was a low incidence of speckle in the loin as a result of the muscle being directly stimulated to contract. The results from this study are consistent with the view that speckle is a result of vigorous movements between muscles during stunning, causing a shearing and rupture of blood vessels in the fat and connective tissues, thus allowing the muscles to squeeze out blood. The incidence of speckle does not appear to be related to blood pressure during stunning. PMID- 22055235 TI - Biochemical factors influencing metmyoglobin formation on beef from muscles of differing colour stability. AB - Biochemical parameters, such as oxygen consumption rate by muscle post mortem (OCR), depth of oxygen penetration into meat, rates of myoglobin oxygenation and deoxygenation and myoglobin content and succinic dehydrogenase activity, were determined for muscles of differing colour stability. Metmyoglobin reduction, in anoxia following oxidation with ferricyanide (MRA) and aerobically following oxidation with low pO(2) (ARA), were also determined. M. psoas major (poor colour stability) has higher enzymic activity than M. longissimus dorsi (good colour stability). This difference, together with the low myoglobin content in M. psoas major, results in relatively high OCR with consequent low oxygen penetration and rapid conversion of oxymyoglobin to myoglobin in M. psoas major, disposing it to rapid formation of metmyoglobin. Metmyoglobin reduction occurs both under anaerobic and aerobic conditions but no significant correlation is found between actual metmyoglobin reduction and rate of discoloration of different muscles. The most significant factor affecting colour stability of beef muscles appears to be their enzymic activity which determines the rate of myoglobin oxidation. PMID- 22055236 TI - Identification of the species origin of fresh meat using an enzyme-linked immunosorbent assay procedure. AB - A modification of indirect enzyme-linked immunosorbent assay (ELISA) has been successfully applied to the detection of horse meat and beef. This technically simple assay requiring species specific antibody, conjugated enzyme anti-IgG and a polystyrene protein-binding solid phase, can be adapted for the identification of meat species in circumstances where laboratory facilities are minimal. PMID- 22055237 TI - The welfare of pigs Edited by W. Sybesma. Martinus Nijhoff, The Hague. 334 pp. 1980. Price not quoted. PMID- 22055238 TI - Developments in food proteins-1 Edited by B. J. F. Hudson, Applied Science Publishers Ltd, London. 335 pp. 1982. Price: L35.00. PMID- 22055239 TI - 3-Alkyl- and 3-amido-isothiazoloquinolin-4-ones as ligands for the benzodiazepine site of GABA(A) receptors. AB - Based on a pharmacophore model of the benzodiazepine binding site of the GABA(A) receptors, developed with synthetic flavones and potent 3-carbonylquinolin-4 ones, 3-alkyl- and 3-amido-6-methylisothiazoloquinolin-4-ones were designed, prepared and assayed. The suggestion that the interaction between the hydrogen bond donor site H1 with the 3-carbonyl oxygen in 3-carbonylquinolin-4-ones can be replaced by an interaction between H1 and N-2 in the isothiazoloquinolin-4-ones, was confirmed. As with the 3-carbonylquinolin-4-ones, the length of the chain in position 3 is critical for an efficient interaction with the lipophilic pockets of the pharmacophore model. The most potent 3-alkyl derivative, 3-pentyl-6 methylisothiazoloquinolin-4-one, has an affinity (K(i) value) for the benzodiazepine binding site of the GABA(A) receptors of 13 nM. However, by replacing the 3-pentyl with a 3-butyramido group an even more potent compound was obtained, with a K(i) value of 2.8 nM, indicating that the amide function facilitates additional interactions with the binding site. PMID- 22055240 TI - The effects of castration, preslaughter stress and zeranol implants on beef: Part 1-The texture of loin steaks from bovine males. AB - A total of 144 male crossbred calves were allocated to four castration or implant treatments (unimplanted bulls; unimplanted steers; bulls implanted with zeranol at 100 days of age and reimplanted at intervals of 69, 93, and 56 days thereafter; bulls implanted with zeranol at 168 days of age and reimplanted at intervals of 93 and 56 days thereafter) and two preslaughter shipping treatments (minimum preslaughter stress with cattle shipped and slaughtered within 4 h of leaving the feedlot pen; normal preslaughter stress with cattle mixed, trucked 160 km, and slaughtered up to 24 h after leaving the feedlot pen). These cattle were slaughtered and striploins of these steaks were removed after 6 days of post mortem aging. Evaluations of these steaks were then conducted using both an experienced laboratory taste panel and a highly trained professional texture profile panel. Results indicated that: (1) the differences that existed in palatability between steaks from unimplanted bulls and steers were primarily due to differences in textural properties directly related to tenderness; (2) increases in preslaughter stress levels were detrimental to the eating quality of both intact males and castrates; (3) zeranol implants had little effect on the textural properties of bull steaks when minimum levels of preslaughter stress were applied; (4) zeranol implants in combination with normal levels of preslaughter stress resulted in steaks which readily broke down to a wide range of particle types many of which were inappropriate and detracted from a well balanced beef texture, thereby more than offsetting the beneficial effects observed on textural properties directly related to tenderness, thus, reducing the texture amplitude; and (5) the influence of the combination of zeranol implants and normal preslaughter stress on textural properties may be manifested through the production of 'dark cutting' beef. PMID- 22055241 TI - The effects of castration, preslaughter stress and zeranol implants on beef: Part 2-Cooking properties and flavor of loin steaks from bovine males. AB - A total of 144 male crossbred calves were allocated to four castration or implant treatments (unimplanted bulls; unimplanted steers; bulls implanted with zeranol at 100 days of age and reimplanted at intervals of 69, 93 and 56 days thereafter; bulls implanted with zeranol at 168 days of age and reimplanted at intervals of 93 and 56 days thereafter) and two preslaughter shipping treatments (minimum preslaughter stress, with cattle shipped and slaughtered within 4 h of leaving the feedlot pen; normal preslaughter stress, with cattle mixed, trucked 160 km, and slaughtered up to 24 h after leaving the feedlot pen). These cattle were slaughtered and striploin steaks were removed after 6 days of post-mortem aging. Evaluations of these steaks were then conducted using both an experienced laboratory taste panel and a highly trained professional flavor profile panel. Results indicated that: (1) steaks from bulls had higher cooking losses than their counterparts from steers, when minimum preslaughter stress was applied; and required longer cooking times under both preslaughter handling treatments; (2) steaks from unimplanted bulls had greater cooking losses and required longer cooking times than their counterparts from implanted bulls under normal preslaughter stress, but not under minimum preslaughter stress; (3) higher proportions of bull steaks than steer steaks contained inappropriate flavor character notes, under both minimum and normal levels of preslaughter stress; (4) both castration and preslaughter handling affected the intensity and order of appearance of specific flavor character notes; (5) the level of preslaughter stress significantly influenced the detection of specific flavor character notes in steaks from both bulls and steers; (6) steaks from steers under minimum preslaughter stress were rated significantly higher in flavor amplitude than their counterparts from bulls when under normal preslaughter stress, and steaks from steers under minimum preslaughter stress received higher flavor desirability scores than steaks from bulls under both minimum and normal preslaughter stress; (7) zeranol implants influenced the appearance and the order of appearance of specific flavor character notes under both minimum and normal levels of preslaughter stress; (8) both zeranol implants and the length of time animals were implanted appeared to increase the intensity of certain inappropriate character notes, and to decrease the intensity of certain appropriate character notes; (9) steaks from implanted bulls received lower flavor amplitude ratings than their counterparts from unimplanted bulls under normal preslaughter stress, but not under minimum preslaughter stress; (10) the level of preslaughter stress influenced both the appearance and order of appearance of specific flavor character notes in both implanted and unimplanted bull steaks; (11) the intensities of certain flavor character notes were influenced by differences in the level of preslaughter stress in both implanted and unimplanted bull steaks, and higher levels usually resulted in inappropriate character notes being more intense; (12) steaks from bulls in both implant groups received lower flavor amplitude ratings when normal preslaughter stress was applied, clearly indicating the deleterious effect of the combination of zeranol implants and normal preslaughter stress on bull beef flavor; and (13) the deleterious effect of the combination of zeranol implants and normal preslaughter stress on bull beef flavor could not be explaind on the basis of greater production of 'dark cutting' beef. PMID- 22055242 TI - Utilization of black gram flour in beef sausages. AB - British fresh beef skinless sausages were prepared in which 30% of the meat, on a protein to protein basis, was replaced by black gram flour. The raw substituted sausages had higher TBA values, were paler in colour and less acceptable than the controls but the general acceptability of the cooked sausages was not affected by the presence of the flour. During storage the substituted sausages discoloured more rapidly than the controls and, in addition, microbial growth became evident sooner. However, moist heat treatment of the flour prior to incorporation in the batter eliminated all these defects so that both the raw and cooked products were as acceptable as the controls. In all sausages, incorporation of black gram flour led to increased cooking losses and softer textures. PMID- 22055243 TI - Chemical fat composition of muscles of the indigenous Nigerian pigs as influenced by age and sex. AB - Seven selected muscles of 96 indigenous Nigeria (32 female, 32 castrated male and 32 intact male) pigs aged between birth and 504 days were analysed for chemical fat. Highly significant age effects were observed for the seven muscles. Statistically significant sex differences were observed for all the muscles except semitendinosus. Generally, fat values for muscles of intact male pigs were lower than for the other two sexes. While non-significant sex-age interactions were observed for biceps femoris, semitendinosus, semimembranosous and longissimus dorsi muscles, highly significant effects were observed for psoas major, triceps brachii and infraspinatus. Growth coefficients b derived from log log regressions of intramuscular fat weight on body weight ranged from an average of 1.088 (R(2) = 0.956) for M. infraspinatus to 1.348 (R(2) = 0.934) for M. biceps femoris and from 0.604 (R(2) = 0.945) to 0.756 (R(2) = 0.941) when related to carcass fat. Average growth coefficients for fore limb muscles were less than for hind limb and spinal column muscles. Fat growth in other depots is reported for comparison with growth of intramuscular fat. PMID- 22055244 TI - Sandwich ELISA for detection of horse meat in raw meat mixtures using antisera to muscle soluble proteins. AB - A double-antibody sandwich ELISA (enzyme-linked immunosorbent assay) has been successfully developed for the detection of defined amounts of horse meat (1-50%) in unheated meat mixtures. The assay uses horse-specific antibodies obtained by immunoadsorption of the crude horse antisera onto immobilised sarcoplasmic extracts from chicken, beef and pig to remove cross-reacting antibodies. The purified antibodies bound to a solid support sequester horse muscle soluble proteins from meat mixtures. Further immunorecognition was made with the same antibodies conjugated to the enzyme horseradish peroxidase. Subsequent enzymic conversion of substrate gave clear optical density differences when assaying mixtures of minced beef and pig containing variable amounts of horse meat. PMID- 22055245 TI - Effect of ingredients on quantitative recovery of Salmonella in raw meat balls. AB - Raw meat balls is a special Turkish meal, prepared from minced meat, bulgar, onion, garlic and different spices. In this experiment raw meat balls were prepared by using minced meat which was inoculated with Salmonella typhimurium at two different levels. Salmonella inoculated minced meat was also used in the experiment as a control. Samples were analysed at intervals. The lowest recovery of Salmonella was observed in raw meat balls which has been inoculated at the higher level. PMID- 22055247 TI - Preterm birth and Assisted Reproductive Technology/ART: maternal emotional wellbeing and quality of mother-newborn interaction during the first three months of life. AB - OBJECTIVE: Assisted Reproductive Technology (ART) and premature birth are stressful and difficult experiences for women. No research to date has examined the impact of ART on mother-child relationship in instances of preterm delivery. This study explored the psychological status of preterm infants' ART-mothers and the quality of mother-infant dyadic interaction, up to child age of three months (Corrected Age = CA). METHOD: Forty-one ART-dyads and 53 Spontaneous Pregnancy (SP) dyads were enrolled. Mother and child were assessed at 5 to 7 days after birth (T1), at child discharge from hospital (T2), at one month after discharge (T3); and at 3 months CA (T4). The following measures were administered to the mothers: the Gordon Personal Profile Inventory, the Beck Anxiety Inventory, the Beck Depression Inventory, and the Parenting Stress Index S-F. Mother-child interaction was coded by using the Nursing Child Assessment Feeding Scale. RESULTS: At childbirth, the control group mothers showed a higher level of anxiety than the ART-mothers did, but at T2, T3, T4, both groups' parenting stress levels were below threshold. Conversely, ART mothers more frequently provided suitable stimulation for their child's socio-emotional and cognitive development than the control group did. No significant between-group differences were observed in the mothers' capacity to respond to their children's distress, nor in sensitivity to child cues. Both infant groups showed equal ability to send clear signals and to respond to parent-provided care. CONCLUSIONS: ART and SP mothers with premature infants showed no differences in degree of emotional burden experienced during the neonatal period. Yet, dyadic interaction was qualitatively better in ART dyads than in SP dyads. PMID- 22055248 TI - Ertapenem in the treatment of bacteremia caused by extended-spectrum beta lactamase-producing Escherichia coli: a propensity score analysis. AB - OBJECTIVE: This study assessed the impact of ertapenem and other carbapenems on mortality in patients with monomicrobial extended-spectrum beta-lactamase producing Escherichia coli (ESBL-EC) bacteremia. METHODS: This non-concurrent prospective study included adult patients with ESBL-EC bacteremia during a 2.5 year period at a 2200-bed teaching hospital. We used a multivariate logistic regression model and Cox's proportional hazards model including propensity score analysis to assess variables associated with 30-day mortality. RESULTS: Of 71 patients who met the study criteria, nine died within 3 days. Among the 62 remaining patients who received definitive antimicrobial therapy, 13 died within 30 days. Male gender, ICU stay, solid tumor, and primary bacteremia were independent predictors of 30-day mortality, whereas definitive antimicrobial therapy using either ertapenem or imipenem/meropenem was protective (p<0.001 and p=0.002, respectively). Adjustment by propensity score found that ertapenem appeared to exhibit more favorable outcomes, but the difference fell short of statistical significance (hazard ratio 0.02, p=0.06). Inappropriate initial therapy was not a significant predictor of mortality. CONCLUSIONS: ICU stay, but not initial choice of empirical antimicrobial therapy, was a major predictor of mortality. Using a carbapenem as definitive therapy was a protective factor for 30-day mortality. The choice of ertapenem is reasonable for less severely-ill patients who are at risk of ESBL-EC bacteremia and unlikely to have infection due to Pseudomonas aeruginosa. PMID- 22055249 TI - Unusual enhancing foci. PMID- 22055250 TI - Abdominal pain and heart failure: a grim diagnosis. PMID- 22055251 TI - Gait asymmetries in children with cerebral palsy: do they deteriorate with running? AB - In children with cerebral palsy (CP) analysis of gait asymmetry can provide insight into the control of walking and may help in guiding the clinician's treatment decisions. Running is more difficult that walking for the musculoskeletal system, however, in the literature it has been shown that gait deviations associated with CP maybe better tolerated during running. This leads us to the hypothesis that running might increase gait symmetry in patients with CP. Therefore the purpose of this study was to investigate the effect of running on asymmetries in spatio-temporal, kinematic and kinetic gait parameters for children with CP. Twenty-four children with diplegia and 25 with hemiplegia were examined using 3D gait analysis during running and walking. MANOVA on two factors: diagnosis (hemiplegic, diplegic) and movement (walking, running) was conducted on a total of 22 gait parameters. The MANOVA revealed a significant difference in symmetry between walking and running (p<0.001) and between patients groups (p=0.004). The detailed analysis of gait parameters demonstrated a significant decrease of symmetry in 13 of the 22 gait parameters investigated, only symmetry of step time was significantly increased. Therefore the hypothesis that gait symmetry improved with running in children with CP can be rejected. Based on the results of this study, asymmetries masked during walking might appear during running. Therefore, analysis of asymmetry of walking and running gives a more comprehensive assessment of the gait pathology for clinical decision making. PMID- 22055253 TI - Effect of frozen storage of minced meats on the quality of sausages prepared from them. AB - Mutton, pork and beef sausages were prepared from minced meats which had been frozen and stored up to 52 weeks at -18 degrees C. There was a significant decrease in texture (W-B shear force) of all the sausages with increased age of the meat. However, concomitantly there were no significant differences in the colour, juiciness or shrinkage (cooking loss) of the sausages. All sausages were organoleptically acceptable even when made from meats stored for 52 weeks at -18 degrees C. PMID- 22055252 TI - The non-invasive and automated detection of bovine respiratory disease onset in receiver calves using infrared thermography. AB - Bovine respiratory disease complex (BRD) causes considerable economic loss and biosecurity cost to the beef industry globally and also results in significant degradation to the welfare of affected animals. The successful treatment of this disease depends on the early, timely and cost effective identification of affected animals. The objective of the present study was to investigate the use of an automated, RFID driven, noninvasive infrared thermography technology to determine BRD in cattle. Sixty-five calves averaging 220 kg were exposed to standard industry practices of transport and auction. The animals were monitored for BRD using conventional biometric signs for clinical scores, core temperatures, haematology, serum cortisol and infrared thermal values over 3 weeks. The data collected demonstrated that true positive animals for BRD based on a gold standard including core temperature, clinical score, white blood cell number and neutrophil/lymphocyte ratio displayed higher peak infrared thermal values of 35.7+/-0.35 degrees C compared to true negative animals 34.9+/-0.22 degrees C (P<0.01). The study also demonstrated that such biometric data can be non-invasively and automatically collected based on a system developed around the animal's water station. It is concluded that the deployment of such systems in the cattle industry would aid animal managers and practitioners in the identification and management of BRD in cattle populations. PMID- 22055254 TI - Characterisation and development of 'the shield' in male pigs. AB - A project was undertaken to characterise boar shield, study its development and determine whether it presents carcass quality problems in young boars used for meat production. In two old boars (>2.5 years) 'backfat' from the scapular region consisted mainly of a dense white tissue with a high collagen content (>20% of fresh weight) and a low lipid content (<10%) compared with normal backfat. Histologically and chemically it resembled the dermis of skin. In a development study in boars and castrates from the Large White and Pietrain breeds, collagen concentration in scapular backfat increased between 91 and 118 kg liveweight in all pigs but the increase was greater in boars than castrates and especially marked in Pietrain boars in which the mean collagen concentration was 18% at 118 kg. This was probably because of the older age of Pietrains since there was a high correlation between age and collagen concentration (r = 0.93). The results suggest that, at 'heavy hog' weights, boar shield could present a carcass quality problem in slow-growing breeds such as the Pietrain. PMID- 22055255 TI - Effect of post-mortem temperature on beef tenderness. AB - Beef adductor muscles were incubated for 4 h post mortem at 10 degrees C and for 4 h and 6 h post mortem at 30 degrees C, 37 degrees C and 42 degrees C. Half of the muscles were cooked just after incubation and the other half was first stored for two days at 4 degrees C and then cooked. Meat kept for 4 h or 6 h at 42 degrees C and for 6 h at 37 degrees C and cooked at once had a significantly (p<0.05) lower shear force than meat kept for 4 h at 37 degrees C, 4 h at 30 degrees C, 6 h at 30 degrees C or 4 h at 10 degrees C. The respective significant differences were also found when the meat was cooked two days after incubation. Organoleptic evaluation showed that meat incubated for 6 h at 37 degrees C or for 4 h at 42 degrees C was not significantly more tender than other samples. However, meat kept for 6 h at 42 degrees C was more tender (p<0.5) than the other samples. After two days of storage, meat incubated for 6 h at 37 degrees C and for 6 h at 42 degrees was more tender (p<0.05) than meat kept for 6 h at 30 degrees C. It was concluded that high temperature conditioning at 37 degrees C or higher for 6 h (4 h at 42 degrees C) just after slaughter makes meat more tender than conventional cooling systems. PMID- 22055256 TI - The effects of various post-mortem treatments on certain physical and sensory properties of three different bovine muscles. AB - Sixty crossbred steers with chronological ages approximating 15 months, carcass weights approximating 270 kg and subcutaneous fat thickness measurements approximating 1.2 cm, were maintained for approximately 210 days on a constantly increasing concentrate ration (13 to 75%, according to NAS nutrient requirements for beef cattle; NAS, 1976). These animals were utilized to evaluate the effects of delayed chilling, hot-boning and electrical stimulation on certain physical, histological, biochemical and sensory properties of three different muscles (Semimembranosus, SM; Longissimus dorsi, LD; and Triceps brachii, TB). Results indicated that neither delayed chilling nor electrical stimulation produced consistent meaningful alterations in any of the physical, cooking or palatability attributes evaluated. However, early post-mortem excision of muscle (hot-boning) consistently produced toughening in all of the muscles evaluated. This was observed to a much greater degree in the TB than in either the SM or LD. Based upon sarcomere length determinations, such toughening could be attributed to cold shortening only in the TB. Electrical stimulation of excised muscle was ineffective in preventing or offsetting this toughening. The delayed chilling treatment imposed (2 h at 12.5 degrees C) was ineffective in enhancing potential effects of electrical stimulation on tenderness. PMID- 22055257 TI - Ultrastructural and biochemical changes in electrically stimulated dark cutting beef. AB - In dark cutting beef, with a high ultimate pH, ultrastructural and biochemical changes were followed during the very early post-mortem period in non-stimulated and electrically stimulated muscles. The consumption of ATP was extremely rapid in the electrically stimulated dark cutting muscle. In these samples pronounced changes in the ultrastructure were seen in the form of heavy contractions and complete disorganization of the tissue. The changes could have been caused by a combined effect of super-contractions and proteolytic activity. The changes seen in electrically stimulated samples were not reflected in improvements of the instrumentally evaluated tenderness. PMID- 22055258 TI - High-sensitivity C-reactive protein: a novel cardiovascular risk predictor in type 2 diabetics with normal lipid profile. AB - BACKGROUND: India is the diabetic capital of the world. Coronary heart disease is a major cause of morbidity and mortality among diabetics. Type 2 diabetes mellitus and atherosclerosis are complex diseases sharing common antecedents like inflammation. High-sensitivity C-reactive protein (hs-CRP), an acute phase reactant protein, is a proinflammatory atherogenic circulating marker which can prove to be an independent cardiac risk predictor. AIM: The aim of the present study was to evaluate the role of hs-CRP as an independent cardiovascular risk marker among Indians with type 2 diabetes with normal lipid profile. SETTINGS AND DESIGN: This was a case control study including 60 type 2 diabetics with normal lipid profile and 60 age- and sex-matched healthy controls. MATERIALS AND METHODS: Twelve-hour fasting blood samples were collected from all the participants. Serum was assayed for hs-CRP and lipid profile. STATISTICAL ANALYSIS: Results were analyzed by unpaired t test. RESULTS: We found elevated hs CRP levels (4.8 +/- 0.2, P < .0001) among cases compared to controls (0.9 +/- 0.1). According to hs-CRP levels, seven cases were in the low-risk (< 1 mg/l), 32 in the moderate-risk (1-3 mg/l), and 21 in the high-risk (3-10 mg/l) group with mean values of hs-CRP of 0.7 +/- 0.2, 1.75 +/- 0.7, and 5.8 +/- 1.4, respectively. Relative risk was 4.75 with odds ratio of 10.23 (95% confidence interval 8.8-11.23). CONCLUSION: The study suggests that hs-CRP is an independent cardiac risk predictor even with normal lipid profile and can help measure additional risk. The American Heart Association stated that patients in the intermediate- and high-risk group may benefit from therapeutic lifestyle change and that cardiovascular event may be prevented. PMID- 22055261 TI - CNS effects following the treatment of malignancy. AB - Corporeal and central nervous system (CNS) axis chemotherapy and radiotherapy have long been used for the effective treatment and prophylaxis of CNS, body malignancies, and leukaemias. However, they are not without their problems. Following the proliferation of magnetic resonance neuroimaging in recent years it has become clear that the spectrum of toxicity that these therapies produce ranges from subclinical white matter changes to overt brain necrosis. The effects are both direct and indirect and via different pathological mechanisms. Chronic and progressive changes can be detected many years after the initial intervention. In addition to leucoencephalopathic changes, grey matter changes are now well described. Changes may be difficult to distinguish from tumour recurrence, though may be reversible and remediable, and are thus very important to differentiate. In this review toxic effects are classified and their imaging appearances discussed, with reference to specific syndromes. PMID- 22055260 TI - Effects of a synthetic retinoid on skin structure, matrix metalloproteinases, and procollagen in healthy and high-risk subjects with diabetes. AB - BACKGROUND: In diabetes, foot ulceration may result from increased skin fragility. Retinoids can reverse some diabetes-induced deficits of skin structure and function, but their clinical utility is limited by skin irritation. The effects of diabetes and MDI 301, a nonirritating synthetic retinoid, and retinoic acid have been evaluated on matrix metalloproteinases (MMPs), procollagen expression, and skin structure in skin biopsies from nondiabetic volunteers and diabetic subjects at risk of foot ulceration using organ culture techniques. METHODS: Zymography and enzyme-linked immunosorbent assay were utilized for analysis of MMP-1, -2, and -9 and tissue inhibitor of metalloproteinase-1 (TIMP 1) and immunohistochemistry for type I procollagen protein abundance. Collagen structure parameters were assessed in formalin-fixed, paraffin-embedded tissue sections. RESULTS: The % of active MMP-1 and -9 was higher and TIMP-1 abundance was lower in subjects with diabetes. Type 1 procollagen abundance was reduced and skin structural deficits were increased in diabetes. Three MUM MDI 301 reduced active MMP-1 and -9 abundance by 29% (P < .05) and 40% (P < .05), respectively, and increased TIMP-1 by 45% (P = .07). MDI 301 increased type 1 procollagen abundance by 40% (P < .01) and completely corrected structural deficit scores. Two MUM retinoic acid reduced MMP-1 but did not significantly affect skin structure. CONCLUSIONS: These data indicate that diabetic patients at risk of foot ulceration have deficits of skin structure and function. MDI 301 offers potential for repairing this skin damage complicating diabetes. PMID- 22055263 TI - Tensile strength of heat-coagulated myosin fibres. AB - Myosin fibres, formed by heat-coagulation under conditions of pH and ionic strength similar to those prevailing in post-rigor meat, exhibited tensile strengths which decreased with fibre diameter. Tensile strengths of the smaller diameter fibres (10-100 MUm) ranged from 30 to 3 kg/cm(2). These values resemble breaking strengths reported for cooked meat (e.g. Davey & Gilbert, 1977) but are an order of magnitude higher than strengths reported for heat-set myosin gels (Nakayama & Sato, 1971) and myosin-bonded meat pieces (Macfarlane et al., 1977). PMID- 22055262 TI - Clinicopathological analysis of head and neck chondrosarcoma: three case reports and literature review. AB - Chondrosarcoma (CHS) is a malignant neoplasm characterized by the formation of cartilaginous matrix by neoplastic cells, with a high propensity for local recurrences. Head and neck CHS is rare, accounting for less than 12% of all cases of CHS, usually affecting the maxilla. The majority of affected patients are in the fourth decade of life, with a slight predilection for male patients. A painless swelling is commonly the most frequent complaint. Surgery with wide en bloc resection is the preferred treatment for CHS; radiotherapy and chemotherapy are usually palliative options. Owing to its rarity, there are few clinical series evaluating the biological behaviour of head and neck CHS. The aim of this study is to analyse the clinicopathological characteristics of head and neck CHS by reporting 3 new cases of this neoplasia affecting the jaw bones and reviewing the clinical series previously published in the English literature. PMID- 22055264 TI - Microbial aspects of protein recovery from meat industry by-products. AB - A significant reduction in the number of micro-organisms associated with the bovine meat by-products, lung, rumen and blood plasma, was noted after their alkali-extractable proteins had been spun into a fibrous form. Most of the effect was found when the protein was coagulated in a 10% acetic acid/10% sodium chloride bath. Whereas the approximate shelf-life of raw rumen and lung was three and four days, respectively (at 0 degrees C), proteins isolated from these tissues were relatively stable and could be stored for up to three weeks. Spun protein fibres were even more resistant to microbial spoilage and were stable for at least three years. Tests for specific food poisoning organisms on the spun protein fibres revealed an absence of coliforms, Staphylococcus aureus and Salmonella/Shigella spp. PMID- 22055259 TI - The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA Diabetes Trial. AB - BACKGROUND: The goal of the VA Diabetes Trial (VADT) was to determine the effect of intensive glucose control on macrovascular events in subjects with difficult to-control diabetes. No significant benefit was found. This report examines predictors of the effect of intensive therapy on the primary outcome in this population. METHODS: This trial included 1791 subjects. Baseline cardiovascular risk factors were collected by interview and the VA record. The analyses were done by intention to treat. FINDINGS: Univariate analysis at baseline of predictors of a primary cardiovascular (CV) event included a prior CV event, age, insulin use at baseline, and duration of diagnosed diabetes (all P < .0001). Multivariable modeling revealed a U-shaped relationship between duration of diabetes and treatment. Modeled estimates for the hazard ratios (HRs) for treatment show that subjects with a short duration (3 years or less) of diagnosed diabetes have a nonsignificant increase in risk (HR > 1.0) after which the HR is below 1.0. From 7 to 15 years' duration at entry, subjects have HRs favoring intensive treatment. Thereafter the HR approaches 1.0 and over-21-years' duration approaches 2.0. Duration over 21 years resulted in a HR of 1.977 (CI 1.77-3.320, P < .01). Baseline c-peptide levels progressively declined up to 15 years and were stable subsequently. INTERPRETATION: In difficult-to-control older subjects with type 2 DM, duration of diabetes altered the response to intensive glucose control. Intensive therapy may reduce CV events in subjects with a duration of 15 years or less and may increase risks in those with longer duration. PMID- 22055265 TI - Influence of processing on the degradation of pesticides in meat products. AB - The influence of processing on the degradation of C-14 labelled DDT, gamma hexachlorocyclohexane (gamma-HCH) and monolinuron (MLN) was investigated. In culture media micrococci and yeasts metabolised DDT, mainly to DDD, within two weeks, whereas gamma-HCH and MLN were negligibly degraded. Only small amounts of the pesticides were metabolised by lactobacilli. Meat of rabbits fed with C-14 labelled pesticides was used to prepare various meat products. In dry sausages with nitrite-curing salt (NCS) up to 60% residual DDT and 70% gamma-HCH were recovered. In the presence of a starter culture and nitrate the rate of degradation was lower, 76% DDT (after 38 days) and 77% of gamma-HCH (after 30 days) of the initial concentrations were found in the final products. In M. Long. dorsi 61% DDT and 80% gamma-HCH were still present after curing. In cured, cooked meats 87% DDT but only 35% gamma-HCH of the initial amounts were left. In the case of MLN about 50% of the radioactivity was removed by curing, hot-smoking or cooking; only 2% of the radioactive material was extracteble. The enzymic degradation of DDT, gamma-HCH and MLN, respectively, by muscle mitochondria (released after freezing) amounted to about 10% on average. In liver sausage mixtures with sodium chloride, DDT and gamma-HCH were metabolised to a greater extent than in mixtures containing NCS or NCS and sodium ascorbate (NaASC). A modified ascorbic acid oxidation system did not enhance the degradation of the pesticides investigated to a significant extent in a cervelat type sausage. PMID- 22055266 TI - A comparison of the Danish MFA, Ulster and optical probes for use in pig carcass classification and grading. AB - The Danish MFA probe and the Ulster probe (UP) automatic recording instruments developed recently for predicting carcass composition in pig classification and grading schemes, were tested in comparison with the optical probe (OP) used at present for this purpose in Great Britain. A series of four fat and two muscle measurements, including the principal ones used in the schemes operated in Denmark, Ulster and Great Britain, was taken on 158 hot carcasses covering the pork, bacon and heavy weight ranges. The standard deviation of carcass weight (W) and percentage lean in carcass were, respectively, 18.9 kg and 4.09 (computed over all data) and 4.51 kg and 3.51 (pooled within weight ranges). There was little difference between instruments in the precision with which they predicted percentage lean, either within weight groups or overall. Residual standard deviations computed over all data for the multiple regression of W and the best individual measurement (fat depth over the M. longissimus at the 3rd/4th last rib) were 2.24 (MFA), 2.44 (UP) and 2.23 (OP). Addition of other measurements to the regression provided only a major improvement in precision. Residual standard deviations for W and all six measurements were 2.15 (MFA), 2.35 (UP) and 2.05 (OP). The relative merits of the three instruments for use in British abattoirs are discussed. PMID- 22055267 TI - Measurement of autolysis in beef muscle homogenates. AB - Homogenates of beef longissimus dorsi muscle have been used to study the effect of pH, temperature and Ca(2+) ions on post-mortem autolysis. Measurements of myofibrillar proteins were made after SDS-polyacrylamide gel electrophoresis and it was found that the intensity of the troponin T band could be used as an indicator of autolysis. At pH values below 6.0, the addition of EDTA increased the rate of loss of troponin T: above pH 6.0, the rate of loss of troponin T was accelerated by Ca(2+) ions. It was concluded that there were at least two proteolytic enzyme systems involved-cathepsin B at low pH and a calcium-activated factor at high pH. PMID- 22055268 TI - Relationship between toughness and troponin T in conditioned beef. AB - During conditioning of beef, the decrease in toughness paralleled the loss of troponin T with time. The rates of increase with temperature gave an energy of activation of 72 kJ/mol for troponin T breakdown and 63 kJ/mol for the reduction in toughness. The extents of reduction of the two components were significantly related; loss of troponin T accounted for about 60% of the variation in toughness. We concluded that measurement of the loss of troponin T rovides a good indicator of the rate and extent of toughness changes during conditioning. PMID- 22055269 TI - Relations between muscle pH and important biochemical parameters during the postmortem changes in mammalian muscles. AB - The relations between muscle pH and the levels of lactate, PC, ATP and free ADP during the development of rigor mortis have been studied in normal beef, sheep, pig and rabbit muscles and, in some cases, in the muscles from stimulated carcasses. There are exponential relations between the PC levels and both the lactate levels and the pH, but these relations have very different slope constants in different muscles, depending on whether the particular muscle was quiescent or active during slaughtering. The slope constants can vary by a factor of three, being very large in quiescent muscles and small in active muscles or in muscles from stimulated carcasses. There is a linear relation between the relative pH or the relative lactate level, on the one hand, and the relative ATP level on the other, which applies generally to all the muscles studied, independent of the extent of glycolysis. In quiescent muscles, the free ADP level increases to about one-tenth of the initial ATP level during the later stages of glycolysis, but only to about one-hundredth of this level in active or stimulated muscles. In quiescent muscles the ATP level begins to decline only at very low levels of PC whereas, in active muscles, the PC level at which this decline begins is some three times greater. Some of the aspects of the differing relations between parameters in different muscles may be explained in terms of differing initial amounts of phosphorylase a. PMID- 22055270 TI - Letter to the editor. PMID- 22055271 TI - The effect of Lactobacillus rhamnosus GG supplemented enteral feeding on the microbiotic flora of preterm infants-double blinded randomized control trial. AB - BACKGROUND AND AIM: Intestinal flora of preterms, dominantly presents with decreased amounts of physiological microbiota. This double blinded randomized control trial compared the stool of bottle fed preterms, randomized to receive lactobacillus rhamnosus GG (LGG) 6x109or placebo with formula feeding. STUDY DESIGN: 46 enterally fed preterms were randomized to receive probiotics or placebo within 0-3days after birth. All personnel were blinded to treatment assignment. Faecal sampling was preformed at day 7, 21, 42. Presence of LGG colonization, somatic growth and length of hospital stay were recorded. RESULTS: 60 patients were initially identified and enrolled but after exclusion criteria were applied, 21 babies were analyzed in the probiotic group and 26 in the placebo group. The number of lactobacillus were significantly higher (p=0.014) on day 7, and 21 (p=0.024) in the study group, and so was the number of enterobacteriaceae on all study days (p=0.004, p=0.000, p=0.000), and Enterococcus sp on day 21 (p=0.000). The amount of samples positive for staphylococci was significantly higher in the study group, on days 7 and 42 (p=0.001 and 0.011). We did not show a significant difference in weight gain upon discharge between the groups p=0.567, 95% CI (-168; 305) or mean of hospital stay p=0.421 95% CI (-13.43;5.71). CONCLUSIONS: A preterm infant formula with an addition of probiotics leads to a rapid growth of LGG in the gut of bottle fed infants, but does not decrease the amount of pathogenic organisms, nor increase weight gain during enteral feeding, or decrease length of hospital stay. PMID- 22055272 TI - Kinematics and early migration in single-radius mobile- and fixed-bearing total knee prostheses. AB - BACKGROUND: The mobile-bearing variant of a single-radius design is assumed to provide more freedom of motion compared to the fixed-bearing variant because the insert does not restrict the natural movements of the femoral component. This would reduce the contact stresses and wear which in turn may have a positive effect on the fixation of the prosthesis to the bone and thereby decreases the risk for loosening. The aim of this study was to evaluate early migration of the tibial component and kinematics of a mobile-bearing and fixed-bearing total knee prosthesis of the same single-radius design. METHODS: Twenty Triathlon single radius posterior-stabilized knee prostheses were implanted (9 mobile-bearing and 11 fixed-bearing). Fluoroscopy and roentgen stereophotogrammetric analysis (RSA) were performed 6 and 12 months post-operatively. FINDINGS: The 1 year post operative RSA results showed considerable early migrations in 3 out of 9 mobile bearing patients and 1 out of 11 fixed-bearing patients. The range of knee flexion was the same for the mobile-bearing and fixed-bearing group. The mobile insert was following the femoral component during motion. INTERPRETATION: Despite the mobile insert following the femoral component during motion, and therefore performing as intended, no kinematic advantages of the mobile-bearing total knee prosthesis were seen. The fixed-bearing knee performed as good as the mobile bearing knee and maybe even slightly better based on less irregular kinematics and less early migrations. PMID- 22055273 TI - Pressure-heat treatment of meat: Changes in myofibrillar proteins and ultrastructure. AB - The effects on muscle of a combined pressure-heat (P-H) treatment that overcomes myofibrillar toughness have been investigated using SDS gel electrophoresis and electron microscopy. Densitometer scans of polyacrylamide gels of muscle extracts revealed that P-H treatment caused greater degradation of connectin than did heat treatment alone. Breakdown of connection by P-H treatment was reduced in muscle that had been injected with the protease inhibitor pepstatin. However, pepstatin treatment did not reduce the effectiveness of P-H treatment for tenderizing meat, as would be expected if connectin was responsible for myofibrillar toughness. P-H treatment resulted in an increase in the intensity of a peak with M(r) ~ 150 000, but this peak was also produced by non-tenderizing pressure treatments. The ultrastructural studies revealed that P-H treatment disrupted the thick and the thin filaments, leaving voids at the M-line region. It is suggested that P-H treatment achieves most of its effect by an irreversible disaggregation of the myosin of thick filaments. PMID- 22055274 TI - Physiological levels of androstenedione and testosterone in some edible tissues from calves, bulls and heifers. AB - The physiological levels of androstenedione and testosterone in muscle, kidney and fat of calves, bulls and heifers were determined by RIA. The androstenedione showed the highest levels in fat and the lowest in muscle tissues. Testosterone showed the same distribution only in male animals, whereas in females the highest levels were in kidney. In fat tissue androstenedione was constantly higher than testosterone in all examined animals. In muscle tissue androstenedione levels were higher than those of testosterone in all female animals and in male calves, whereas testosterone was higher in bulls. Testosterone was the main androgen in kidney tissue in both young and adult animals, irrespective of sex. PMID- 22055275 TI - Chronological age and breed-type effects on carcass characteristics and palatability of bull beef. AB - Bulls (n = 115) of four slaughter ages (9, 12, 15 or 18 months) and of 15 genotypes were studied. In this analysis, each bullock was assigned to one of four breed groups-British and British crosses, Brahman and Brahman crosses. Jersey and Jersey crosses or Holstein and Holstein crosses. Slaughter age had an (P < 0.01) effect on marbling score, longissimus muscle area, fat thickness and yield grade while breed group had an (P < 0.01) effect on marbling score and quality grade. In general, British and British cross bullocks produced carcasses with the thickest subcutaneous fat, the highest marbling score and the highest USDA quality grade while Jersey and Jersey cross bullocks yielded carcasses with the lowest weight, smallest longissimus muscle area and the lowest USDA quality grade of the four breed-type groups. Increases in chronological age (from 9 to 18 months) were generally associated with a decrease in USDA maturity score, and increases in marbling score, USDA quality grade, longissimus muscle area, subcutaneous fat thickness and USDA yield grade. Shear force values decreased as bulls matured from 9 to 18 months of age. The meat from Brahman-type bulls had higher shear force values (P < 0.01) than that from bulls of the other breed groups. Steaks from British-type carcasses received the highest numerical ratings for sustained juiciness and flavor while steaks from the Brahman-type carcasses were assigned the lowest numerical ratings for juiciness. Breed-type had a greater effect on tenderness of bull beef than did chronological age. PMID- 22055276 TI - Effect of ascorbate and ascorbyl palmitate on lipid oxidation in semi-dry saugages manufactured from pork materials differing in stability towards oxidation. AB - Semi-dry fermented sausages were manufactured from three batches of pork slightly differing in their polyenoic fatty acid levels and alpha-tocopherol contents. The sausage doughs were treated as follows: (1) control, (2) ascorbate, (3) ascorbyl palmitate and (4) a combination of ascorbate and ascorbyl palmitate. After brine fermentation, products ripened at 15 degrees C were evaluated for rancidity by peroxide values and TBA numbers. During ripening important differences in stability towards oxidation were generally not observed. Both peroxide and TBA values gradually increased linearly with time. For the TBA values, gradients for the products derived from the three diet groups differed considerably. Only two of six batches containing increased levels of alpha-tocopherol and product antioxidants exhibited slightly improved stability towards oxidation, as judged by peroxide and TBA values. Sensory evaluations, performed only on the product series containing ascorbate, failed to reveal any positive effect in favour of the increased alpha-tocopherol content. Thus, for semi-dry sausages manufactured from pork materials with a slightly increased sensitivity towards oxidation, results indicated with there was little advantage to increasing the levels of alpha-tocopherol in the meat by dietary means or to changing the current commercial practice of adding ascorbate to the sausage doughs. PMID- 22055277 TI - Water distribution in porcine M. longissimus dorsi in relation to sensory properties. AB - The water distribution in M. longissimus dorsi (LD) from purebred Hampshire and Swedish Yorkshire pigs was recorded by proton-pulse-NMR. Three domains of water were seen with this type of method, designated as free, extracellular and intracellular water, respectively. The relative proton population for the free water increased from 1.8% in raw, to 3.3% in fried, samples from Hampshire and to 4.2% for the Yorkshire samples. The relaxation time of the extracellular water increased for Hampshire samples from 100 ms, when raw, to 108 ms and 114 ms for samples fried to centre temperatures of 68 degrees C and 80 degrees C, respectively. For Yorkshire samples it decreased from 122 to 108 and 109 ms, respectively. The relative proton population of the extracellular water decreased after frying (raw: 24.5%, 68 degrees C: 18.6% and 80 degrees C: 13.9%) for Hampshire samples, whereas the corresponding populations of protons for those of Yorkshire were 16.5%, 19.2% and 16.6%. The intracellular water had relaxation times of about 40 ms (raw), 30 ms (68 degrees C) and 28 ms (80 degrees C) for both breeds. The relative proton populations were: for Hampshire, 74.1% (raw), 77.7% (68 degrees C), 83.4% (80 degrees C) and, for Yorkshire, 81.6% (raw), 75.5% (68 degrees C) and 77.2% (80 degrees C). On average, the samples of Hampshire were more juicy and tender than those of Yorkshire. The sensory properties were related to the water distribution, but obvious influences of breed and end-point temperature at frying were noted for the relationships. In general, the juiciness and tenderness of fried LD samples could fairly well be predicted by the water distribution in raw meat. However, due to the influence of breed and temperature, different variables are best for the prediction. Also, when the sensory properties were related to the water distribution in fried samples, the influences of breed and end-point temperatures were noted. PMID- 22055279 TI - Inhalation of hydrogen gas attenuates cisplatin-induced ototoxicity via reducing oxidative stress. AB - OBJECTIVE: Cisplatin, an anticancer drug used extensively to treat a broad range of tumors, has strong ototoxic side effects induced by reactive oxygen species (ROS). Recently, it has been reported that hydrogen gas (H(2)) is a new antioxidant by selectively reducing hydroxyl radical, the most cytotoxic ROS. The present study was designed to investigate whether H(2) treatment is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress. METHODS: The animals were intraperitoneally given a 30 min infusion of 16 mg/kg cisplatin or the same volume of saline. H(2) treatment was given twice with 2% H(2) inhalation for 60 min starting at 1h and 6h after cisplatin or saline injection, respectively. The hearing status of all animals was evaluated by auditory brainstem responses (ABR). The hair cell damage was observed by phalloidin staining. In addition, the levels of oxidative products in serum and cochlear tissue were measured. RESULTS: We found that H(2) treatment significantly attenuated cisplatin-induced hearing loss evaluated by click-evoked and tone burst ABR threshold. Furthermore, histological analysis revealed that 2% H(2) treatment significantly alleviated cisplatin-induced hair cell damage in the organ of corti. In addition, cisplatin significantly increased the levels of malondialdehyde (MDA) and 8-iso prostaglandin F2alpha (8-iso-PGF2alpha) in serum and cochlear tissue, which was attenuated by H(2) treatment. CONCLUSION: These results demonstrate that H(2) is beneficial to cisplatin-induced ototoxicity via reducing oxidative stress. Therefore, H(2) has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the cisplatin ototoxicity. PMID- 22055280 TI - Attention training toward and away from threat in social phobia: effects on subjective, behavioral, and physiological measures of anxiety. AB - Social phobics exhibit an attentional bias for threat in probe detection and probe discrimination paradigms. Attention training programs, in which probes always replace nonthreatening cues, reduce attentional bias for threat and self reported social anxiety. However, researchers have seldom included behavioral measures of anxiety reduction, and have never taken physiological measures of anxiety reduction. In the present study, we trained individuals with generalized social phobia (n = 57) to attend to threat cues (attend to threat), to attend to positive cues (attend to positive), or to alternately attend to both (control condition). We assessed not only self-reported social anxiety, but also behavioral and physiological measures of social anxiety. Participants trained to attend to nonthreatening cues demonstrated significantly greater reductions in self-reported, behavioral, and physiological measures of anxiety than did participants from the attend to threat and control conditions. PMID- 22055281 TI - Internet-delivered or mailed self-help treatment for insomnia?: a randomized waiting-list controlled trial. AB - Cognitive Behavioral Therapy (CBT) is effective in reducing insomnia complaints, but the effects of self-help CBT have been inconsistent. The aim of this study was to determine the effectiveness of self-help for insomnia delivered in either electronic or paper-and-pencil format compared to a waiting-list. Participants kept a diary and filled out questionnaires before they were randomized into electronic (n = 216), paper-and-pencil (n = 205), or waiting-list (n = 202) groups. The intervention consisted of 6 weeks of unsupported self-help CBT, and post-tests were 4, 18, and 48 weeks after intervention. At 4-week follow-up, electronic and paper-and-pencil conditions were superior (p < .01) compared to the waiting-list condition on most daily sleep measures (Deltad = 0.29-0.64), global insomnia symptoms (Deltad = 0.90-1.00), depression (Deltad = 0.36-0.41), and anxiety symptoms (Deltad = 0.33-0.40). The electronic and paper-and-pencil groups demonstrated equal effectiveness 4 weeks after treatment (Deltad = 0.00 0.22; p > .05). Effects were sustained at 48-week follow-up. This large-scale unsupported self-help study shows moderate to large effects on sleep measures that were still present after 48 weeks. Unsupported self-help CBT for insomnia therefore appears to be a promising first option in a stepped care approach. PMID- 22055282 TI - Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: rapid lesion necrosis followed by lesion-specific immune response. AB - Current topical agents for field therapy of actinic keratoses have single mechanisms of action and must be applied for weeks. Ingenol mebutate gel, a novel drug for field therapy of actinic keratoses, appears to have a dual mechanism of action: (1) rapid lesion necrosis and (2) specific neutrophil-mediated, antibody dependent cellular cytotoxicity. Because of the rapid destruction of actinic keratosis lesions after application of ingenol mebutate gel, treatment is necessary for only 2 or 3 days. The subsequent immune-mediated response targets any residual dysplastic epidermal cells. This dual mechanism of action should provide efficacy equivalent to that of current topical agents with a substantially shorter treatment period. PMID- 22055283 TI - Recommendations and current practices for the reconstitution and storage of botulinum toxin type A. AB - BACKGROUND: Current guidelines from the Centers for Disease Control and Prevention (CDC) regarding the reconstitution and storage of botulinum toxin type A (BT-A) differ from those of the Centers for Medicare and Medicaid Services and current clinical practice. CDC guidelines require single-patient use of BT-A vials. Strict adherence to these guidelines creates waste and a significant financial impediment, and does not confer increased protection from infection, assuming standard safe injection practices are followed. OBJECTIVE: This study examines current clinical practices and provides expert consensus recommendations regarding the reconstitution and storage of BT-A. A review of the literature on the sterility and efficacy of BT-A stored beyond the recommended time period of 4 hours is also presented. METHODS: An Internet-based survey was used to analyze the current practices of physician members of the American Society for Dermatologic Surgery who administer botulinum type A toxins. RESULTS: After reconstitution, the majority of physicians (68.6%) routinely store BT-A for a period of greater than 1 week and safely use each toxin vial for more than one patient. Not a single case of infection was observed. LIMITATIONS: This was a single survey with a 32.2% response rate. CONCLUSION: A single vial of BT-A can be safely administered to multiple patients, assuming standard safe injection techniques are followed. After reconstitution, Our data suggest that BT-A can be stored beyond the recommended time period of 4 hours. PMID- 22055284 TI - The effect of pre-slaughter showering and post-slaughter rapid chilling on meat quality in intact pork sides. AB - Thirty pairs of Landrace or Large White pigs were used to determine the effects of pre- and post-slaughter cooling treatments on pork quality and yield. One animal from each pair was showered in cold water and after slaughter one side from each carcass was rapidly chilled and the other side was conventionally chilled. Two experiments were carried out in winter: they examined different times of exposure to cooling treatments; a further experiment was carried out in summer time. Showering caused a reduction in the temperature of the deep loin at 40 min post mortem (P < 0.01). Rapid chilling caused a further reduction in carcass temperature and the rate of pH fall was lower (P < 0.05) in the rapidly chilled sides. There was a strong indication that showering in the winter time lowered drip loss in slices of Longissimus dorsi muscle (P = 0.077) whereas showering in the summer time was not effective. Shower water temperature may have been important in this regard. Showering did not lower drip loss in intact pork legs. Rapid chilling was not effective in lowering drip loss in either slices of Longissimus dorsi or intact pork legs. Rapid chilling at -20 degrees C for 3 h without an air blast lowered evaporative chill losses in sides of pork by 27-29% (P < 0.1) compared to normal chilling. Reduced treatments gave reduced effects. Neither treatment had any significant effect on cooking loss or toughness in broiled slices of pork Longissimus dorsi muscle. PMID- 22055285 TI - Effect of salt on myoglobin derivatives in the sarcoplasmic extract from pre- and post-rigor beef in the presence or absence of mitochondria and microsomes. AB - The effect of salt and pH on the colour stability (oxymyoglobin) in the sarcoplasmic extract (SPE) prepared from pre- and post-rigor beef muscle was studied in the presence or absence of mitochondria and microsomes during 96 h at 4 degrees C. The sarcoplasmic extract from the post-rigor meat (pH 5.4) or from the pre-rigor meat adjusted to pH 5.4 contained more oxymyoglobin (MbO(2)) than the pre- or post-rigor SPE maintained at pH 7.4. The presence or absence of mitochondria and microsomes in the SPE at pH 5.4 had little effect on the percentage of MbO(2). At pH 7.4, however, the percentage of MbO(2) decreased in the SPE in the presence of mitochondria, whereas the percentage of MetMb was lower in the presence of microsomes. The relative proportion of MbO(2) decreased and that of metmyoglobin (MetMb) increased with increasing salt concentration at low pH (more so in the absence of subcellular organelles) and with storage period in the SPE from both pre- and post-rigor meat. However, at pH 7.4, high levels of salt (2-4%) helped to maintain a high percentage of MbO(2) in SPE in the absence of subcellular organelles, especially the mitochondria. The first-order interactions of pH value * subcellular organelles (P < 0.01) and pH value * salt concentration (P < 0.01) accounted for about 55% of the total variation in the percentage of MbO(2) in the SPE. It is suggested that depressing microbial growth may be the operative mechanism by which added salt stabilizes the colour in pre rigor minced meat rather than by enzymic effects of subcellular organelles. PMID- 22055286 TI - Comparison of EEG and ECoG for detecting cerebrocortical activity during slaughter of calves. AB - Parallel electrocorticograms (ECoG) and electroencephalograms (EEG) were recorded during stun-recovery and stun-slaughter of eight calves 4-6 weeks old. Epochs of 8.2 s duration, derived from the ECoG and EEG signals pre-stun, during recovery and during exsanguination, were compared for differences in power content and frequency distribution using Fast Fourier Transform analysis. ECoG signals recorded during the quiescent phase post-stun had a markedly lower power content compared with pre-stun, whereas the EEG signal showed no such reduction in power content. During exsanguination, the mean rate of decline in the ECoG power content was 0.025 log units/s, three times faster than the mean rate of decline of the EEG at 0.008 log units/s. The duration of the electroplectic fit post-stun was detected equally well by the two techniques. The differences between EEG and ECoG traces in this study are thought to arise from differences in the signal noise ratio of the two techniques and by artefacts in the EEG signal, caused by microscopic movement between EEG electrodes and the surrounding tissue. The slower rate of decline in the power content of the EEG during slaughter means that the time to onset of isoelectric cortical electrical activity will be longer if determined by EEG measurements than by ECoG recording. PMID- 22055287 TI - Comparison of Duroc and British landrace pigs for meat a and eating quality. AB - Duroc and halothane negative British Landrace boars and gilts were performance tested from 30 to 80kg on ad-libitum or restricted feeding regimes, with like sexed non-littermate groups of pigs penned together. Meat and eating quality was determined using objective laboratory measurements and by taste panel and consumer panel assessment on 160 pigs with 20 full-sib families for each breed, and two boars and two gilts per family. Duroc M. longissimus(?) was darker in colour, had a more intense, redder colour and contained more fat and less moisture than Landrace muscle. Duroc subcutaneous fat was less firm, had a higher water content and concentrations of linoleic acid and lower concentrations of stearic acid than Landrace fat. The taste and consumer panels scored Duroc meat as being more juicy, but less tender, having poorer flavour and being less acceptable than Landrace meat. The higher juiciness scores of Duroc meat were probably attributable to the higher intramuscular fat content compared to Landrace meat. Duroc boars had lower values for flavour liking and acceptability compared to other breed-sex combinations which may be due to the particular fatty acid composition of the subcutaneous fat in Duroc boars. PMID- 22055288 TI - An estimate of the incidence of dark cutting beef in the United Kingdom. AB - Eight slaughterplants with throughputs ranging from 20 to 300 animals per day were examined to estimate the incidence of dark cutting beef in the United Kingdom. Four thousand, eight hundred and sixteen animals were surveyed and information concerning animal category, source, season and preslaughter handling conditions recorded. Muscle samples were removed to estimate glycogen concentration and after incubation, ultimate pH. The overall incidence of dark cutting (pHu >= 6.0) was 4.1%. Increased incidence was associated with short (<= 20 miles) and long (>= 150 miles) transport distances. Slaughter on the day of arrival rather than overnight lairage also increased the incidence. Plants were classified into small (killing <= 50 animals per day) or large (killing >= 100 per day). Eighty per cent of the animals slaughtered passed through the large plants, and a higher incidence was also associated with these plants. Bulls had the highest incidence and heifers the lowest. A seasonal effect was recorded with the highest incidence found between July and October. The results, however, indicate that factors in addition to those examined are also important. PMID- 22055289 TI - Computerized diffractometer for measurements of sarcomere lengths in meat: An evaluation of data reduction methods. AB - A computerized laser diffractometer was evaluated on the basis of two different theoretical models for light diffraction in muscle tissue. It was shown that the method of computing sarcomere lengths from the positions of the left and right first order diffraction lines is model dependent. Sarcomere lengths obtained by the diffractometer were compared to microscopically determined sarcomere lengths on freeze-sectioned M. sternomandibularis from a material consisting of muscle strips held at different degrees of stretch. Treating left and right diffraction lines as independent observations led to the determination of sarcomere lengths with negligible deterministic error. The possibility of utilizing the fine structure and intensity of the diffraction patterns to improve the sarcomere length determination and provide more relevant information is discussed. PMID- 22055291 TI - Spikes in retinal bipolar cells phase-lock to visual stimuli with millisecond precision. AB - BACKGROUND: The conversion of an analog stimulus into the digital form of spikes is a fundamental step in encoding sensory information. Here, we investigate this transformation in the visual system of fish by in vivo calcium imaging and electrophysiology of retinal bipolar cells, which have been assumed to be purely graded neurons. RESULTS: Synapses of all major classes of retinal bipolar cell encode visual information by using a combination of spikes and graded signals. Spikes are triggered within the synaptic terminal and, although sparse, phase lock to a stimulus with a jitter as low as 2-3 ms. Spikes in bipolar cells encode a visual stimulus less reliably than spikes in ganglion cells but with similar temporal precision. The spike-generating mechanism does not alter the temporal filtering of a stimulus compared with the generator potential. The amplitude of the graded component of the presynaptic calcium signal can vary in time, and small fluctuations in resting membrane potential alter spike frequency and even switch spiking on and off. CONCLUSIONS: In the retina of fish, the millisecond precision of spike coding begins in the synaptic terminal of bipolar cells. This neural compartment regulates the frequency of digital signals transmitted to the inner retina as well as the strength of graded signals. PMID- 22055292 TI - The exoribonuclease Nibbler controls 3' end processing of microRNAs in Drosophila. AB - MicroRNAs (miRNAs) are endogenous noncoding small RNAs with important roles in many biological pathways; their generation and activity are under precise regulation [1-3]. Emerging evidence suggests that miRNA pathways are precisely modulated with controls at the level of transcription [4-8], processing [9-11], and stability [12, 13], with miRNA deregulation linked with diseases [14] and neurodegenerative disorders [15]. In the Drosophila miRNA biogenesis pathway, long primary miRNA transcripts undergo sequential cleavage [16-18] to release the embedded miRNAs. Mature miRNAs are then loaded into Argonaute1 (Ago1) within the RNA-induced silencing complex (RISC) [19, 20]. Intriguingly, we found that Drosophila miR-34 displays multiple isoforms that differ at the 3' end, suggesting a novel biogenesis mechanism involving 3' end processing. To define the cellular factors responsible, we performed an RNA interference (RNAi) screen and identified a putative 3'->5' exoribonuclease CG9247/nibbler essential for the generation of the smaller isoforms of miR-34. Nibbler (Nbr) interacts with Ago1 and processes miR-34 within RISC. Deep sequencing analysis revealed a larger set of multi-isoform miRNAs that are controlled by nibbler. These findings suggest that Nbr-mediated 3' end processing represents a critical step in miRNA maturation that impacts miRNA diversity. PMID- 22055293 TI - The 3'-to-5' exoribonuclease Nibbler shapes the 3' ends of microRNAs bound to Drosophila Argonaute1. AB - BACKGROUND: MicroRNAs (miRNAs) are ~22 nucleotide (nt) small RNAs that control development, physiology, and pathology in animals and plants. Production of miRNAs involves the sequential processing of primary hairpin-containing RNA polymerase II transcripts by the RNase III enzymes Drosha in the nucleus and Dicer in the cytoplasm. miRNA duplexes then assemble into Argonaute proteins to form the RNA-induced silencing complex (RISC). In mature RISC, a single-stranded miRNA directs the Argonaute protein to bind partially complementary sequences, typically in the 3' untranslated regions of messenger RNAs, repressing their expression. RESULTS: Here, we show that after loading into Argonaute1 (Ago1), more than a quarter of all Drosophila miRNAs undergo 3' end trimming by the 3'-to 5' exoribonuclease Nibbler (CG9247). Depletion of Nibbler by RNA interference (RNAi) reveals that miRNAs are frequently produced by Dicer-1 as intermediates that are longer than ~22 nt. Trimming of miRNA 3' ends occurs after removal of the miRNA* strand from pre-RISC and may be the final step in RISC assembly, ultimately enhancing target messenger RNA repression. In vivo, depletion of Nibbler by RNAi causes developmental defects. CONCLUSIONS: We provide a molecular explanation for the previously reported heterogeneity of miRNA 3' ends and propose a model in which Nibbler converts miRNAs into isoforms that are compatible with the preferred length of Ago1-bound small RNAs. PMID- 22055294 TI - UVA phototransduction drives early melanin synthesis in human melanocytes. AB - Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% ultraviolet A (UVA) and ~5% ultraviolet B (UVB) at the Earth's surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or phospholipase C (PLC) inhibitors or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to 5-fold after 24 hr. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis and may underlie the mechanism of IPD in human skin. PMID- 22055295 TI - Hippocampal-prefrontal connectivity predicts midfrontal oscillations and long term memory performance. AB - The hippocampus and prefrontal cortex interact to support working memory (WM) and long-term memory [1-3]. Neurophysiologically, WM is thought to be subserved by reverberatory activity of distributed networks within the prefrontal cortex (PFC) [2, 4-8], which become synchronized with reverberatory activity in the hippocampus [1, 4]. This electrophysiological synchronization is difficult to study in humans because noninvasive electroencephalography (EEG) cannot measure hippocampus activity. Here, using a novel integration of EEG and diffusion weighted imaging, it is shown that individuals with relatively stronger anatomical connectivity linking the hippocampus to the right ventrolateral PFC (ventral Brodmann area 46) exhibited slower frequency neuronal oscillations during a WM task. Furthermore, subjects with stronger hippocampus-PFC connectivity were better able to encode the complex pictures used in the WM task into long-term memory. These findings are consistent with models suggesting that electrophysiological oscillations provide a mechanism of long-range interactions [9] and link hippocampus-PFC structural connectivity to PFC rhythmic electrical dynamics and memory performance. More generally, these results highlight the importance of incorporating individual differences when linking structure and function to cognition. PMID- 22055296 TI - Treatment of pseudobulbar affect with citalopram in a patient with progressive multifocal leukoencephalopthy. AB - Pseudobulbar affect (PBA) manifests in a variety of neurologic illnesses suggesting a heterogeneous pathophysiology with common underpinnings. We report successful treatment of PBA with a selective serotonin reuptake inhibitor (SSRI) in a 54-year-old woman following progressive multifocal leukoencephalopathy (PML). In light of recent focus on dextromethorphan/quinidine (DM/Q) for the treatment of PBA, the clinician is reminded of the effectiveness of SSRIs. PMID- 22055297 TI - Collagen content of meat carcasses of known history. AB - Thirteen beef carcasses and twenty-seven pig carcasses were analysed for collagen content. The beef carcasses were drawn from four breeds and four levels of fatness. They were dissected into ten joints: from the forequarter; shin, brisket, Jacob's ladder, clod, sticking, fore-rib, chuck: from the hindquarter; leg, thin flank and other joints. Samples of each joint were analysed for fat, moisture and collagen. Samples of the total forequarter and hindquarter meat were also analysed. The pig carcasses were drawn from three weight groups and three levels of fatness. Samples from each carcass were analysed for fat, moisture and collagen. Six selected pigs were dissected into five joints: hand, collar, back, streak and ham. Samples of each joint were analysed as described above. Results from beef carcasses showed that collagen in the forequarter (3.2% wet fat-free) was significantly higher than in the hindquarter (2.7% wet fat-free). Within the forequarter collagen in the shin (4.8% wet fat-free) was significantly higher than in the other six joints. Within the hindquarter percentage collagen was significantly highest in the leg (4.2% wet fat-free). There were no significant breed differences. Results from pig carcasses showed an overall mean value for collagen of 2.3% wet fat-free. Percentage collagen was significantly highest in the hand (2.9% wet fat-free). PMID- 22055298 TI - Low voltage electrical stimulation and post-mortem energy metabolism in beef. AB - In the present study, the influence of low voltage electrical stimulation on glycolysis, concentrations of creatine phosphate and adenine nucleotides, as well as the relationship between metabolic activity and tenderness, was examined in bovine M. longissimus dorsi. During stimulation, about 50% of the creatine phosphate was consumed and the immediate pH drop was, on average, 0.21 units. The increased energy consumption resulted in a decrease in the halftime of ATP from 10 h in non-stimulated muscles to 5 h in electrically stimulated muscles. The total high energy phosphate turnover was found to be 2400 MUmol/h/g during stimulation and 18 MUmol/h/g immediately following stimulation compared with 9 MUmol/h/g for the non-stimulated counterpart. No obvious abnormalities were found in the course of changes during energy metabolism following stimulation, besides the increased metabolic rate. Significant relationships were found between the degradation of several of the energy metabolites during stimulation and improvements in tenderness. It is concluded that, within the variation found in this study, the better the effect of electrical stimulation in increasing the metabolic rate, the better the resulting meat tenderness. Results also showed that the higher the shear force in the non-stimulated part, the better was the effect of electrical stimulation in improving the meat tenderness. PMID- 22055299 TI - Post-mortem glycolysis in rabbit Longissimus dorsi muscles following electrical stimulation. AB - The effects of both high voltage and low voltage electrical stimulation were studied in rabbit Longissimus dorsi muscles. The rate of fall of pH as well as the activities of phosphorylase a, phosphorylase kinase, and phosphorylase phosphatase were measured. The effects on the yield, ATPase activities, and calcium permeability of the sarcoplasmic reticulum (SR) were also measured. Although only high voltage stimulation increased the post-stimulation rate of pH fall, both types of electrical stimulation increased the phosphorylase a activity, apparently by increasing the activity of phosphorylase kinase and destroying a large part of the phosphorylase phosphatase activity. Electrical stimulation reduced the yield of SR and increased its basal ATPase activity. It also increased the ability of the SR to retain accumulated calcium. We conclude that the different rates of pH fall observed following the two types of stimulation are due to the differential effects of these treatments on one of the ATPase activities, probably the myofibrillar ATPase. PMID- 22055300 TI - The effects of electrical stimulation and ageing on beef tenderness. AB - Seventeen beef carcasses from cattle with a range of breeds, ages and body conditions were used in this trial. The four treatments applied to each carcass were control (C), electrical stimulation (ES), ageing for 28 days (A) and electrical stimulation plus ageing for 28 days (ES + A). Post-mortem muscle pH was measured at 0, 0.5, 4 and 24h post-stimulation. Significantly lower muscle pH values (P < 0.01) were achieved by the stimulated carcass side sompared to the unstimulated side at 0.5 (pH 6.47 vs. 6.91) and 4 h (pH 5.96 vs. 6.44) post stimulation. Warner-Bratzler shear and taste panel methods were used to assess the tenderness of Longissimus dorsi muscle samples from each of the four treatments. The ES, A and ES + A treatments were significantly more tender (P < 0.01) than the control treatment. The ES and the A treatments resulted in a similar improvement in tenderness compared to the control. The ES + A treatment was significantly more tender (P < 0.01) than the ES treatment alone, but there was no significant difference in tenderness between the A and the ES + A treatments. PMID- 22055301 TI - The reduction of boar taint in male pigs by neonatal testosterone administration. AB - Ten neonatal male pigs were treated with 100 mg of testosterone propionate, and the effects of the treatment on endocrine function, carcass fatness, meat and fat composition were studied. No important changes were found in carcass fatness or in chemical composition of the M. longissimus dorsi. Fatty acid composition of the backfat was modified in the treated pigs, with a decrease in palmitoleic (P < 0.001) and oleic (P < 0.05) acids and an increase in stearic acid (P < 0.05); consequently, the fat had a higher melting point (P < 0.05). Neonatal treatment with testosterone propionate led to a decrease in testicle weight (P < 0.05), testosterone concentration (P < 0.05) and luteinizing hormone (LH) secretion in the hypophysis (P < 0.001). Histological evidence of modification of the intertubular area in the testicle was found (P < 0.001). Decrease of endocrine secretion in the testes led to a reduction in the levels of detectable boar taint in treated animals, as assessed by sensory evaluation. PMID- 22055302 TI - Immersion chilling of hot cut, vacuum packed pork primals. AB - Hot-cutting and immersion chilling of pork was compared with a conventional air chilling process. The right sides of eight pig carcasses were cut into primals whilst hot, vacuum packed and chilled in sodium chloride brine at 0 degrees C, whilst the left sides were chilled conventionally in air at 0 degrees C and 1 m/s, before being similarly cut and vacuum packed. The primals from both treatments were then stored in air at 0 degrees C for either 24h or 15 days post mortem. The immersion process achieved an average saving in weight loss of 1.9% after both storage periods, and took between 2.5 and 3.5 h less than the conventional process to reduce meat temperatures to 7 degrees C. It did, however, produce significantly tougher meat after 24 h, although not after 15 days. Sensory evaluation of odour and appearance suggested a reduced shelf-life and a darker meat coloration for immersion chilled pork. PMID- 22055303 TI - The influence of mechanically deboned meat and pH on the water-holding capacity and texture of emulsion type meat products. AB - The influence of the amount of mechanically deboned pork meat (MDM) on the quality of model 'Frankfurters' was studied, and the relationship between the pH of the blends versus the texture and water-holding capacity (WHC) of the finished products was investigated. In the experiments 2.9%, 5.8% and 11.6% pork loin were exchanged with MDM. It was found that addition of MDM increased the pH and the WHC, and that moderate addition of MDM resulted in greater yield stress and elasticity modulus, while higher concentrations of MDM resulted in very soft texture. The pH of the meat blends was very important for the functional properties of the pasteurized products. It made no difference whether pH was determined by the meat raw materials alone or adjusted through addition of NaOH or MDM. PMID- 22055304 TI - Establishing microbiological surveillance programmes at slaughterlines-A new concept of meat hygiene. AB - This paper examines the practical aspects of a concept for microbiological control of dressing operations on cattle slaughterlines. First, the spreading of Salmonella was examined. A total of 99 (3.66%) of the swab samples were positive. Cutting off the hooves and pre-skinning showed the highest recovery of Salmonella. A second survey included the detection of all the important groups of the surface microflora. The microbiological profiles of the carcasses were determined at the end of the slaughterline and after different stages of chilling. A consistently higher contamination was found statistically for the lateral surface of the carcasses and, within this area, the most contaminated sites were on the front quarter. The biometrical analysis revealed a significant interaction between contamination and site, and an indicator function of the total viable count (TVC) and the Enterobacteriaceae. The TVC (x = 4.95/s = 0.34 cfu/cm(2)) indicated a fairly good standard of slaughter hygiene. Correct chilling did not change the contamination rates very much. This increased contamination is a result of improper handling of the carcasses. The trends of both surveys demonstrate that, for cattle slaughter, the establishing of critical control points is a possible way for a plant to control the slaughterline. PMID- 22055305 TI - Prevention of dark-cutting (DFD) beef in penned bulls at the abattoir. AB - There is a large body of evidence indicating that activities associated with regrouping of bulls before slaughter, which leads to physical exhaustion mainly from mounting, are primary factors inducing dark-cutting (DFD) in beef. The aim of this study was to test several methods to control activity when regrouping cannot be avoided. Fifty bulls previously individually tied for at least 16 months were drafted into groups of five animals and released in a pen at the abattoir. After 18 to 22 h they were slaughtered. According to environmental conditions in the pen, the bulls were divided into four groups: Control group (n = 10, no experimentation); Electricity group (n = 10, an electric fence was constructed above the pen so that a mounting bull would receive an electric shock); Darkness group (n = 10, the whole stall was in darkness); and Combination group (n = 20, both treatments, of the electricity and darkness groups were applied). During the first hour of penning the behaviour of the bulls was videorecorded. After slaughter meat quality characteristics were measured. Dark cutting was found in Control (70%), Electricity (30%) and Darkness (70%) groups, but not in the Combination group (0%). No treatment altered the repertoire of agonistic activity, but under the combined treatments the number of agonistic interactions was significantly lower than in any other group. PMID- 22055306 TI - The determination of hydroxyproline in meat using gas chromatography-mass spectrometry. AB - A method is described for the determination of 4-hydroxyproline in meat using gas chromatography-mass spectrometry. The amino acid is converted into its N(O) trifluoroacetyl n-propyl ester, gas chromatography being carried out with the mass spectrometer in the selected ion monitoring (SIM) mode giving high sensitivity and selectivity for the hydroxyproline derivative. PMID- 22055307 TI - Response of bovine muscles to direct high voltage electrical stimuli. AB - Left sides of beef carcasses were stimulated (ES) using multiple-contact electrodes for both the positive and negative electrodes. These electrodes were attached to the carcass side in the neck and shoulder (arm) region (positive electrodes) and the hindquarter (round) region (negative electrodes). Stimulation was generated using 600 V, 60 Hz, 2.8 A alternating current for a duration of 2 min (impulses: 2 s on and 2 s off). Right sides served as controls. Carcass sides were chilled at 2 degrees C. Stimulated sides showed a more rapid pH fall during the first 5 h post-stimulation in the longissimus dorsi, semimembranosus, semitendinosus, biceps femoris and triceps brachii (long head) muscles. Lower shear values for muscles in direct contact with the ES electrodes were observed compared to controls, except in the case of the semitendinosus muscle, where no difference was found. Data from the present study suggest that muscles, which quite often do not respond to ES and do not exhibit an improvement in tenderness, perhaps because they may not be located in the current pathway, can show improvements in tenderness if the current is distributed in the direction of these muscles. However, a muscle's response to the electrical stimuli, with the accompanying rapid decline in pH, does not necessarily ensure a significant improvement in tenderness. PMID- 22055308 TI - Jugular blood flow in calves after head-only electrical stunning and throat cutting. AB - Jugular flow was measured after head-only electrical stunning and gash cutting in 12 calves less than a week old. Jugular flow was assumed to provide a crude measure of cerebral perfusion during exsanguination. In 10 animals the average amount of jugular blood collected within 1-2 min of throat-cutting was the equivalent of a total cerebral blood flow of 3.6 ml/min/100 g +/- 1.4 SD or 4.8% of normal. In two animals the jugular flow was increased to 39% and 22% of normal cerebral flow. All animals had strong retrograde flow from the head ends of the cut carotid arteries. The dynamics of cerebral blood perfusion are discussed with reference to systemic arterial blood pressure and spontaneous cortical electrical activity, and some potentially fruitful areas of research on the humaneness of halal slaughter of cattle are proposed. PMID- 22055309 TI - Photosensitized degradation of caffeine: role of fulvic acids and nitrate. AB - The photolysis of caffeine was studied in solutions of fulvic acid isolated from Suwannee River, GA (SRFA) and Old Woman Creek Natural Estuarine Research Reserve, OH (OWCFA) with different chemical amendments (nitrate and iron). Caffeine degrades slowly by direct photolysis (>170 h in artificial sunlight), but we observed enhanced photodegradation in waters containing the fulvic acids. At higher initial concentrations (10 MUM) the indirect photolysis of caffeine occurs predominantly through reaction with the hydroxyl radical (OHi) generated by irradiated fulvic acids. Both rate constant estimates based upon measured OHi steady-state concentrations and quenching studies using isopropanol corroborate the importance of this pathway. Further, OHi generated by irradiated nitrate at concentrations present in wastewater effluent plays an important role as a photosensitizer even in the presence of fulvic acids, while the photo-Fenton pathway does not at neutral or higher pH. At lower initial concentrations (0.1 MUM) caffeine photolysis reactions proceed even more quickly in fulvic acid solutions and are influenced by both short- and long-lived reactive species. Studies conducted under suboxic conditions suggest that an oxygen dependent long lived radical e.g., peroxyl radicals plays an important role in the degradation of caffeine at lower initial concentration. PMID- 22055310 TI - Sorption comparison between phenanthrene and its degradation intermediates, 9,10 phenanthrenequinone and 9-phenanthrol in soils/sediments. AB - The degradation intermediates of phenanthrene (PHE) may have increased health risks to organisms than PHE. Therefore, environmental fate and risk assessment studies should take into considerations of PHE degradation products. This study compared the sorption properties of PHE and its degradation intermediates, 9,10 phenanthrenequinone (PQN) and 9-phenanthrol (PTR) in soils, sediments and soil components. A relationship between organic carbon content (f(OC)) and single point sorption coefficient (logK(d)) was observed for all three chemicals in 10 soils/sediments. The large intercept in the logf(OC)-logK(d) regression for PTR indicated that inorganic fractions control PTR sorption in soils/sediments. No relationship between specific surface area and K(d) was observed. This result indicated that determination of surface area based on gas sorption could not identify surface properties for PHE, PQN, and PTR sorption and thus provide limit information on sorption mechanisms. The high sorption and strong nonlinearity (low n values) of PTR in comparison to PHE suggested that the mobility of PTR could be lower than PHE. Increased mobility of PQN compared with PHE may be expected in soils/sediments because of PQN lower sorption. The varied sorption properties of the three chemicals suggested that their environmental risks should be assessed differently. PMID- 22055311 TI - Occurrence and accumulation patterns of polycyclic aromatic hydrocarbons and synthetic musk compounds in adipose tissues of Korean females. AB - Very few studies have reported on the occurrence and accumulation profiles of polycyclic aromatic hydrocarbons (PAHs) and synthetic musk compounds (SMCs) in human adipose tissue. In this study, concentrations of PAHs and SMCs in adipose tissues collected from Korean women in 2007 and 2008 were determined. Total concentrations of PAHs and SMCs in adipose tissues ranged from 15 to 361 (mean: 119) ngg(-1) lipid weight and from 38 to 253 (mean: 106) ngg(-1) lipid weight, respectively. Concentrations of SMCs in Korean adipose tissues were lower than those reported for European countries and the United States. Naphthalene was the most predominant PAH and HHCB was the dominant SMC found in adipose tissues. The concentrations of PAHs and SMCs were not correlated with each other, suggesting that the sources of human exposure to these two classes of compounds are different. No correlation was found between donor's age and residue levels of PAHs and SMCs. The results of this study provide baseline information on exposure of PAHs and SMCs to the general population in Korea. PMID- 22055312 TI - A comparison of exposure methods for SPME-based bioavailability estimates. AB - The ability of polydimethlysiloxane coated solid phase microextraction (SPME) fibers to predict bioavailability has been documented for a number of species and compounds. There are also a variety of established methods for establishing SPME based bioavailability estimates; however, factors such as time until equilibrium and exposure regimen could affect fiber concentrations and have not yet been thoroughly tested. Exposure time may influence SPME fiber concentrations at equilibrium. Co-exposure of the fibers with different animals or the invertebrate species used could yield different estimates than those acquired using a shaker table system to achieve equilibrium between the sediment and SPME fibers. The current study examined the effects of time and exposure method (shaker table versus co-exposure with test species) on SPME fiber concentrations for two hydrophobic compounds: permethrin and p,p'-dichlorodiphenyldichloroethylene (DDE). An additional experiment with permethrin determined whether animal densities or fiber number influenced fiber concentrations. There were significant differences between the time required for SPME fibers to reach equilibrium when co-exposed with different species or separately, but fiber concentrations at equilibrium among treatments for both compounds were similar. Furthermore, among the 12 variations in species and fiber densities, there were no significant differences among treatments indicating that neither the route of exposure, animal density, nor fiber volume influenced SPME fiber estimates. This demonstrated that SPME fiber concentrations at equilibrium were not affected by exposure conditions, increasing their versatility in environmental assessments. PMID- 22055313 TI - Enrofloxacin oxidative degradation facilitated by metal oxide nanoparticles. AB - The activity of copper oxide, titanium carbide and silicon nitride nanoparticles for the oxidative degradation of environmentally relevant concentrations (MUg L( 1) range) of enrofloxacin - an important veterinary antibiotic drug - in aqueous solutions was investigated. With hydrogen peroxide as an oxidative agent, both copper oxide and titanium carbide decrease the concentration of enrofloxacin by more than 90% over 12 h. Addition of sodium halide salts strongly increases the reaction rate of copper oxide nanoparticles. The mechanism for the formation of Reactive Oxygen Species (ROS) was investigated by Electron Spin Resonance (ESR). PMID- 22055314 TI - Assessment of a process to degrade metal working fluids using Pseudomonas stutzeri CECT 930 and indigenous microbial consortia. AB - The development of a novel biological process to treat metal working fluids (MWFs)-containing effluents at bioreactor scale was pursued in this work. The bacteria Pseudomonas stutzeri CECT 930 was investigated for the first time as an alternative agent for MWF degradation. An adequate medium design and mixing and aeration system, as well as an appropriate microorganism proved to be crucial for reaching high levels of degradation by P. stutzeri and by an indigenous consortium (about 70% and 50% of reduction in total petroleum hydrocarbon content in less than 2 wk, respectively). Additionally, as there is no information in literature trying to kinetically characterize an MWF-polluted effluent degradation process, all the experimental data were fitted to logistic and Luedeking and Piret models, that allowed to elucidate the growth-associated character of the biodegradation process. PMID- 22055315 TI - Mechanochemical degradation of gamma-hexachlorocyclohexane by a planetary ball mill in the presence of CaO. AB - Although the use of the insecticide gamma-hexachlorocyclohexane (HCH) is now prohibited in many countries because of its hazardousness, stockpiles of gamma HCH still exist. In this study, we subjected gamma-HCH to mechanochemical (MC) treatment with a planetary ball mill in the presence of CaO to investigate the feasibility of using this method for the treatment of gamma-HCH stockpiles. We confirmed the degradation of gamma-HCH and investigated the degradation mechanism. The major intermediates were identified to be 1,3,4,5,6 pentachlorocyclohexene (gamma-PCCH) and chlorobenzenes (CBzs). Analysis of the steric structure of gamma-HCH and identification of the degradation intermediates suggested that successive dehydrochlorination led to the formation of trichlorobenzenes. Products of further degradation (dichlorobenzenes, monochlorobenzene, and benzene) were also detected. Surprisingly, methane and ethane were also detected, which suggests cleavage of the C-C bonds of the cyclohexane ring and hydrogenation. All of the chlorine atoms in the gamma-HCH could be transformed into inorganic chloride compounds by the MC treatment with CaO. Our results indicate that gamma-HCH can be completely dechlorinated by MC treatment. PMID- 22055316 TI - The microbiology of hot and conventionally deboned vacuum packed beef. AB - The mean numbers of aerobic bacteria were not significantly different from hot or cold, vacuum packed deboned beef, initially or on storage at 0 and 5 degrees C. This was observed for both the psychrotrophic (4 degrees C) and mesophilic (25 degrees C) portions of the flora. It was possible to distinguish between the mean numbers of aerobes stored at 0 and 5 degrees C. There were significantly higher numbers of facultative anaerobes and, in particular, lactobacilli, on hot boned cuts and for the latter organisms the psychrotrophs were predominant. For B. thermosphacta, there was no difference between cuts from hot or cold deboned beef. An accurate estimate of the psychrotrophic flora could be obtained from the mesophilic counts. PMID- 22055317 TI - Effects of N-nitrosopyrrolidine, nitrite and pyrrolidine on tumour development in mice as related to ingestion of cured meat. AB - The incidence of tumours in mice fed a standard chow diet and given either N nitrosopyrrolidine (NPyr), nitrite (NO(2)) or nitrite plus pyrrolidine (NO(2) + Pyr) in the drinking water for 12 months at 100mg, 1 g and 1 g plus 100mg/litre, respectively, was compared with that for a control group (C) receiving no additives. Differences between groups in weight gain and feed consumption were not significant. Group 3 (NO(2)) drank less water (P < 0.05) than those in groups 1 (C) and 2 (NPyr). Water intake of mice in group 4 (NO(2) + Pyr) did not differ from that of any of the other three groups. Survival rates were: 94% (C), 80% (NPyr), 92% (NO(2)) and 83% (NO(2) + Pyr); but the differences were not statistically significant. Gross examination upon autopsy revealed that the incidence of all tumours in group 2 (NPyr) was 10- to 20-fold higher than that in any other group. Histological examination confirmed that NPyr induced more (P < 0.05) malignant tumours in liver and lungs with any other treatment; otherwise there were no significant differences. Results indicated that NO(2) + Pyr (nitrite plus a secondary amine) did not increase the frequency of carcinogenic tumours in mice. PMID- 22055318 TI - Ca(2+)-activated protease in stored muscle. AB - To establish the role of Ca(2+)-activated protease (CAF) in meat tenderness, the properties of CAF extracted from stored muscle, and the effects of CAF on the ultrastructure of myofibrils under the conditions obtaining in stored muscle were studied. The yield and activity of crude CAF extracted from stored muscle were higher than that from muscle immediately post mortem, but no difference of the enzymic properties (time course of activity, pH dependence and Ca(2+) dependence) was observed between the two preparations. An electron microscopic study of the effects of CAF on myofibril structure indicated that CAF was active under the conditions actually obtaining in stored muscle. From the results obtained in this paper, it was confirmed that the CAF had an important role in meat tenderness. PMID- 22055319 TI - The analysis of protein in fresh meats using pulsed NMR. AB - The protein content of fresh meats was estimated using a pulsed nuclear magnetic resonance (NMR) spectrometer in conjunction with an alkali copper relaxation reagent. The standard deviations on all meat samples, which differed widely in fat content, were less than 0.5% in protein. A single calibration line, with a correlation coefficient of 0.999, was obtained using three lean meats. This calibration sufficed to determine the protein content of three meats with a high fat content, the results of which were in close agreement with the corresponding Kjeldahl values. PMID- 22055320 TI - Pathways of high and low voltage electrical stimulation in sheep carcasses. AB - Using the neuromuscular blocking agent, curare, the involvement of the nervous system in the transmission of high (850 V peak) and low voltage (45 V peak) electrical stimulation in sheep carcasses was studied. Post-mortem metabolism in the Longissimus dorsi, Semitendinosus and Semimembranosus muscles was followed by measuring changes in pH, adenosine triphosphate, creatine phosphate, inorganic phosphate and hexose monophosphate. Stimulation was considered to be effective if it accelerated glycolysis. Low voltage stimulation of glycolysis was completely inhibited by curare, indicating that a functional nervous system is required for effective stimulation by low voltages. In contrast, high voltage stimulation of glycolysis was not affected by curare, indicating that high voltages exert their effect by depolarising the cell membrane directly. PMID- 22055321 TI - Rate of freezing effect on the colour of frozen beef liver. AB - One problem that arises when freezing liver in plate freezers in the whitish colour acquired by the liver surface when subjected to high freezing rates. The purpose of this paper aims to establish optimum operating conditions for freezing beef liver pieces in a minimum time while maintaining an acceptable colour on the surface. Samples were subjected to different freezing rates and minimum surface freezing time was established in order to obtain an acceptable colour. This was quantified in terms of lightness using a surface colorimeter. Histological analysis of the samples showed that the size of the ice crystals formed on the contact surface with the coolant is the factor that determines the changes in colour as a result of diffused light reflection phenomena. On the basis of mathematical heat transfer models with simultaneous change of phase, the minimum characteristic surface freezing time was related to the process operating variables (initial temperature of the liver, coolant temperature, interfacial heat transfer resistance, thickness of the piece), and the optimum freezing conditions were determined, reducing total processing times to a minimum. PMID- 22055323 TI - Thornton's meat hygiene by J. F. Gracey. Bailliere Tindall, 7th edn. 436 pp., 106 Figures, 23 Tables, 4 colour plates. 1981. Price: L18.00. PMID- 22055322 TI - Predicting cutability of packer-trimmed pork loins. AB - This study explored the possibility of determining retail yields of packer trimmed pork loins by the use of either a swine backfat probe or the Hennessy and Chong Fat Depth Indicator. The standard deviation for retail yield in this study was 3.82. Regression equations developed to predict percentages of retail yield from pork loins produced residual standard deviations that ranged from 4.20 to 2.94. Low to intermediate relationships were found between fatness measurements and percentages of fat-free lean from packer-trimmed pork loins. Prediction equations utilising the Fat Depth Indicator predicted retail yield percentages with greater precision than did a swine backfat probe (2.94 versus 3.33, respectively). PMID- 22055324 TI - The problem of dark-cutting beef Edited by D. E. Hood and D. V. Tarrant. Martinus Nijhoff, Publishers BV, The Hague, The Netherlands. xi + 504 pp. 1981. Price: US$43. PMID- 22055325 TI - Meat, poultry and seafood technology, recent developments, food technology review no. 56 by E. Karmas. Noyes Data Corporation, Park Ridge, New Jersey. xv + 427 pp. 1982. Price not quoted. PMID- 22055327 TI - Erratum. PMID- 22055328 TI - Ultrasound for low temperature dyeing of wool with acid dye. AB - The possibility of reducing the temperature of conventional wool dyeing with an acid levelling dye using ultrasound was studied in order to reach exhaustion values comparable to those obtained with the standard procedure at 98 degrees C, obtaining dyed samples of good quality. The aim was to develop a laboratory method that could be transferred at industrial level, reducing both the energy consumption and fiber damage caused by the prolonged exposure to high temperature without the use of polluting auxiliary agents. Dyeings of wool fabrics were carried out in the temperature range between 60 degrees C and 80 degrees C using either mechanical or ultrasound agitation of the bath and coupling the two methods to compare the results. For each dyeing, the exhaustion curves of the dye bath were determined and the better results of dyeing kinetics were obtained with ultrasound coupled with mechanical stirring. Hence the corresponding half dyeing times, absorption rate constants according to Cegarra-Puente modified equation and ultrasonic efficiency were calculated in comparison with mechanical stirring alone. In the presence of ultrasound the absorption rate constants increased by at least 50%, at each temperature, confirming the synergic effect of sonication on the dyeing kinetics. Moreover the apparent activation energies were also evaluated and the positive effect of ultrasound was ascribed to the pre exponential factor of the Arrhenius equation. It was also shown that the effect of ultrasound at 60 degrees C was just on the dye bath, practically unaffecting the wool fiber surface, as confirmed by the results of SEM analysis. Finally, fastness tests to rubbing and domestic laundering yielded good values for samples dyed in ultrasound assisted process even at the lower temperature. These results suggest the possibility, thanks to the use of ultrasound, to obtain a well equalized dyeing on wool working yet at 60 degrees C, a temperature process strongly lower than 98 degrees C, currently used in industry, which damages the mechanical properties of the fibers. PMID- 22055329 TI - Mental health, substance use and intimate partner problems among pregnant and postpartum suicide victims in the National Violent Death Reporting System. AB - OBJECTIVES: Suicide during pregnancy and postpartum is a tragic event for the victim and profoundly impacts the baby, the family and the community. Prior efforts to study risks for pregnancy-associated suicide have been hampered by the lack of data sources which capture pregnancy and delivery status of victims. Introduction of the United States National Violent Death Reporting System (NVDRS) offers new insights into violent deaths by linking multiple data sources and allowing better examination of psychosocial risk factors. METHODS: The analysis used data from 17 states reporting to the NVDRS from 2003 to 2007 to evaluate suicide patterns among pregnant, postpartum, and nonpregnant or postpartum women. Demographic factors, mental health status, substance use, precipitating circumstances, intimate partner problems and suicide methods were compared among groups. RESULTS: The 2083 female suicide victims of reproductive age demonstrated high prevalence of existing mental health diagnosis and current depressed mood, with depressed mood significantly higher among postpartum women. Substance use and presence of other precipitating factors were high and similar among groups. Intimate partner problems were higher among pregnant and postpartum victims. Postpartum women were more likely to die via asphyxia as cause of death compared to poisoning or firearms. CONCLUSIONS: These findings describe important mental health, substance use and intimate partner problems seen with pregnancy associated suicide. The study highlights mental health risk factors which could potentially be targeted for intervention in this vulnerable population. PMID- 22055330 TI - Hidden depression in otolaryngology patients with medically unexplained symptoms. AB - OBJECTIVE: To investigate the prevalence of depression among otolaryngology patients with medically unexplained symptoms (MUS) and the outcome of treatment with selective serotonin reuptake inhibitors (SSRIs). METHOD: Ninety patients with MUS from a population of 983 consecutive otolaryngology outpatients were enrolled. The Self-Rating Depression Scale (SDS) was used to screen for depression. In addition to standard treatment, all depressed and nondepressed patients received SSRIs for 8 weeks. The Clinical Global Impression-Improvement (CGI-I) scale was used to evaluate clinical changes in patients with MUS. RESULTS: There were 49 patients with depression among those with MUS, according to the SDS criteria. The patients with depression showed a better outcome than those without depression, demonstrating more significantly improved CGI-I scores. CONCLUSION: More than half of the individuals with otolaryngological MUS had depression, and their MUS were successfully treated with SSRIs. PMID- 22055331 TI - Three-year mortality of delirium among elderly inpatients in consultation-liaison service. AB - OBJECTIVE: The purpose of this study is to assess 3-year mortality in delirious patients receiving consultation-liaison service in a general hospital setting. METHODS: We consecutively enrolled inpatients 65 years of age and older that were referred for psychiatric consultation (N=614) from 2002 to 2006. One hundred and seventy-two patients were diagnosed with delirium. The exact date of death was based on the registration data from the Department of Health, Executive Yuan, in Taiwan and was used to calculate the mortality rate and time to death (days) after psychiatric consultation. Furthermore, the 1-year, 2-year and 3-year mortality rates of delirious patients were compared to mortality rates of nondelirious patients. Factors (e.g., age, length of hospital stay, gender, physical illness, use of antipsychotics) were analyzed by using the Cox proportional hazard model to identify possible associations with mortality. RESULTS: Delirious patients had a higher mortality rate each year than nondelirious patients. After analysis, 1-year mortality was significantly higher in the delirious group than in the nondelirious group (P=.043), but 2-year and 3 year mortality rates were not significantly different when comparing the delirious and nondelirious groups (P=.149; P=.439). In the Cox proportional hazard regression analysis, 1-year mortality in delirious patients was significantly associated with older age and length of hospital stay (P<.001), but not with gender, physical comorbidity or use of antipsychotics. CONCLUSION: These results suggest that elderly delirious inpatients in psychiatric consultation service had significantly higher mortality than nondelirious inpatients, especially in the first year after consultation. Clinical physicians should pay close attention to delirious patients, especially those with mortality-related risk factors, in order to reduce mortality in these patients. PMID- 22055332 TI - The diagnostic challenge of frontotemporal dementia in psychiatric patients: a case report. AB - Frontotemporal dementia (FTD) is often misdiagnosed early in the clinical course and may be confused with primary psychiatric disorders. This is especially true when patients have a psychiatric history. In this report, we describe a case that illustrates the diagnostic challenge of FTD in a patient with a history of obsessive-compulsive disorder. PMID- 22055333 TI - Cytokine changes in the pathophysiology of poststroke depression. AB - OBJECTIVE: Poststroke depression (PSD) is a frequent psychiatric sequela after stroke, and its influence is detrimental. However, the etiology of PSD is still not clear. Although many studies have indicated that immune dysregulation plays an important role in the pathophysiology of depression, it is still unknown if PSD involves the same mechanism. Thus, the current study objectives were to evaluate whether there were cytokine changes when patients with ischemic stroke suffered from PSD. METHOD: We included ischemic stroke patients without depression when the stroke occurred and followed them for 1 year. The Hamilton Depression Rating Scale score and cytokines were assessed at baseline and at the 1st, 3rd, 6th, 9th and 12th months after stroke. RESULTS: One hundred four patients with ischemic stroke participated and completed the study, and 12 suffered from PSD during the 1-year study period. There were significant increases in the cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and interferon-gamma, and the ratios of IL-6/IL 10 and TNF-alpha/IL-10 were also elevated. Interleukin-1beta was too low to show any difference. CONCLUSION: Our study suggested that immune imbalance plays a possible role in the pathophysiology of PSD and that IL-6 and TNF-alpha are key cytokines. PMID- 22055334 TI - Propranolol in yawning prophylaxis: a case report. AB - OBJECTIVE: Yawning is a frequent behavior with circadian effects. Sometimes, its frequency is very high and it is disturbing. However, there is no evidence-based treatment for yawning. METHOD: This is a case report of a man with severe yawning from about 2 years ago. RESULTS: Yawning reduced after taking propranolol. CONCLUSION: Current evidence suggests that propranolol may decrease yawning through its thermoregulation effect. It is worthwhile conducting controlled clinical trials to study whether propranolol is an effective treatment for yawning. PMID- 22055336 TI - Normative fetal brain growth by quantitative in vivo magnetic resonance imaging. AB - OBJECTIVE: The objective of the study was to characterize total and regional volumetric brain growth in healthy fetuses during the second and third trimesters of pregnancy, using an automated method. STUDY DESIGN: We developed and validated an automated method to quantify global and regional in vivo brain volumes using fetal magnetic resonance imaging. We then computed the percentage of growth for each brain structure in a cohort of 64 healthy fetuses (25.4-36.6 weeks' gestational age). RESULTS: The cerebellum demonstrated the greatest maturation rate, with a 4-fold increase (384%) in volume between 25.4 and 36.6 weeks, and a relative growth rate of 12.87% per week. Both total brain and cerebral volumes increased by 230% and brain stem volume by 134% over the same gestational age period. Conversely, lateral ventricular volume decreased by 4.18% per week. CONCLUSION: The availability and ongoing validation of normative fetal brain growth trajectories will provide important tools for early detection of impaired fetal brain growth upon which to manage high-risk pregnancies. PMID- 22055337 TI - Is comprehensive surgical staging needed for thorough evaluation of early-stage ovarian carcinoma? AB - OBJECTIVE: Patients with ovarian cancer may have occult metastasis at the time of surgery. Our purpose was to determine the prevalence and sites of occult metastasis in epithelial ovarian cancer grossly confined to the ovary and examine the significance of routine omentectomy and peritoneal biopsies as part of a comprehensive staging procedure. STUDY DESIGN: Data were retrospectively abstracted from patients presenting to University of Texas Southwestern Medical Center Hospitals from 1993 through 2009 with ovarian cancer without gross spread beyond the ovary who underwent comprehensive surgical staging. RESULTS: A total of 86 patients with ovarian cancer grossly confined to the ovary who underwent complete surgical staging were identified. Of patients, 29% were upstaged following comprehensive surgical staging; 6% had metastatic disease in uterus and/or fallopian tubes, 6% in lymph nodes, and 17% in peritoneal, omental, or adhesion biopsies. CONCLUSION: Patients with epithelial ovarian cancer should continue to undergo comprehensive surgical staging, since it identifies occult metastasis in a significant number of patients. PMID- 22055338 TI - Can placental growth factor in maternal circulation identify fetuses with placental intrauterine growth restriction? AB - OBJECTIVE: We investigated whether decreased concentrations of placental growth factor (PlGF) in maternal circulation differentiated placental intrauterine growth restriction (IUGR) from constitutionally small fetuses. Excluding congenital syndromes, infection, and aneuploidy, we assumed IUGR with an abnormal placental pathology to be of placental origin. STUDY DESIGN: The study design included a single site, case-control study of 16 cases (9 placental IUGR, 7 constitutionally small) and 79 normal controls with singleton pregnancies. Plasma PlGF was measured by Triage PlGF immunoassay according to the product insert. A positive PlGF test was defined as a concentration less than the fifth percentile for gestational age for normal pregnancy. RESULTS: A positive PlGF test was found in 9 of 9 placental IUGR cases, 1 of 7 constitutionally small fetuses, and 4 of 79 controls (P < .0001). PlGF identified placental IUGR from constitutionally small fetuses with 100% sensitivity and 86% specificity (P = .0009). CONCLUSION: These preliminary data suggest PlGF may identify placental IUGR antenatally. PMID- 22055339 TI - Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial. AB - OBJECTIVE: The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system. STUDY DESIGN: We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis. RESULTS: There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84-0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17-1.34). CONCLUSION: The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo. PMID- 22055340 TI - Exhausting attentional tracking resources with a single fast-moving object. AB - Driving on a busy road, eluding a group of predators, or playing a team sport involves keeping track of multiple moving objects. In typical laboratory tasks, the number of visual targets that humans can track is about four. Three types of theories have been advanced to explain this limit. The fixed-limit theory posits a set number of attentional pointers available to follow objects. Spatial interference theory proposes that when targets are near each other, their attentional spotlights mutually interfere. Resource theory asserts that a limited resource is divided among targets, and performance reflects the amount available per target. Utilising widely separated objects to avoid spatial interference, the present experiments validated the predictions of resource theory. The fastest target speed at which two targets could be tracked was much slower than the fastest speed at which one target could be tracked. This speed limit for tracking two targets was approximately that predicted if at high speeds, only a single target could be tracked. This result cannot be accommodated by the fixed-limit or interference theories. Evidently a fast target, if it moves fast enough, can exhaust attentional resources. PMID- 22055341 TI - Soluble CXCL16 and long-term outcome in acute ischemic stroke. AB - OBJECTIVE: CXCL16 is a chemokine involved in atherosclerosis by promoting inflammation, lipid accumulation and matrix degradation. The level of circulating CXCL16 has been proposed as a predictor of long-term mortality in acute coronary syndromes. We studied plasma CXCL16 in acute ischemic stroke and examined associations with long-term mortality following the acute event. METHODS: CXCL16 samples were obtained from 244 patients with acute ischemic stroke (age: 69+/-13 years) daily from presentation to day 5 and at half a year after the stroke. Patients with overt ischemic heart disease and atrial fibrillation were excluded. The patients were followed for 47 months, with all-cause and cardiovascular (CV) mortality as end-points. RESULTS: At follow-up, 72 patients had died with 43 due to CV causes. Plasma CXCL16 was stably elevated in the first days after the acute event followed by a marked decrease after 6 months. In patients who subsequently suffered an adverse outcome, CXCL16 levels at 4 days after the initial event were elevated and were moderately associated with mortality. The increase in CXCL16 from day 1 to 4 was a predictor for all-cause and, in particular, CV mortality even after adjustment in the multivariate analysis for established risk factors such as age, the presence of heart/renal failure, troponin, C-reactive protein and stroke severity. CONCLUSIONS: An increase in plasma CXCL16 during the first days after the initial event is associated with an adverse outcome in patients with acute ischemic stroke, supporting the potential pathogenic role of CXCL16 in atherosclerosis and vascular remodelling as well as their major clinical consequences. PMID- 22055342 TI - Properties and characteristics of P(VDF/TrFE) transducers manufactured by a solution casting method for use in the MHz-range ultrasound in air. AB - Highly effective piezoelectric polymer transducers operating in air at high frequencies have been successfully made by casting a solution of ferroelectric poly(vinylidene fluoride-co-trifluoroethylene) P(VDF/TrFE) directly on a backing metal plate, and their performance has been evaluated. By utilizing this method, it has been possible to develop the three kinds of transducers that operate respectively at 4, 6 and 10MHz in air. For precise evaluation of the performance of the P(VDF/TrFE) transducers, the absorption loss in air was measured up to 10MHz. It was confirmed that the empirical formula obtained from the measured absorption values in air at high frequencies was in alignment with its theoretical value. In addition, a high lateral resolution acoustic image of a ROM Chip (amplitude-image) at 6MHz in air was successfully displayed using an air coupled concave type P(VDF/TrFE) transducer by bonding an epoxy adhesive. PMID- 22055343 TI - Binary regulation of Hippo pathway by Merlin/NF2, Kibra, Lgl, and Melted specifies and maintains postmitotic neuronal fate. AB - Patterning the Drosophila retina for color vision relies on postmitotic specification of photoreceptor subtypes. R8 photoreceptors express one of two light-sensing Rhodopsins, Rh5 or Rh6. This fate decision involves a bistable feedback loop between Melted, a PH-domain protein, and Warts, a kinase in the Hippo growth pathway. Here, we show that a subset of the Hippo pathway-Merlin, Kibra, and Lethal(2)giant larvae (Lgl), but not Expanded or Fat-is required for Warts expression and activity in R8 to specify Rh6 fate. Melted represses warts transcription to disrupt Hippo pathway activity and specify Rh5 fate. Therefore, R8 Hippo signaling exhibits ON-or-OFF regulation, promoting mutually exclusive fates. Furthermore, Merlin and Lgl are continuously required to maintain R8 neuronal subtypes. These results reveal roles for Merlin, Kibra, and Lgl in neuronal specification and maintenance and show that the Hippo pathway is reimplemented for sensory neuron fate by combining canonical and noncanonical regulatory steps. PMID- 22055345 TI - Compounds determining pH in dry sausage. AB - The relative importance of various compounds determining pH in dry sausage was investigated using 'multiple linear regression' analysis. Analytical data were obtained for the concentrations of water, lactate, ammonia, acetate, alpha-amino nitrogen and salt related to sausage crude protein, using 55 different brands of dry sausage. The pH (Y) was significantly related to water, ammonia and lactate concentrations as follows: Y = 4.317 - 1.152X(1) + 0.751X(2) where X(1) = log(H(2)O) and X(2) = [log (ammonia)/(lactate) . 100] with (H(2)O) expressed as g/100g crude protein and (lactate) and (ammonia) as mmoles/100 g crude protein. The results suggest that the increase in pH often observed in the later stages of ripening is related to a decrease in electrolyte dissociation and/or an increase in the concentration of buffering proteins as well as to the formation of ammonia. PMID- 22055346 TI - Effect of body fat distribution on the fatty acid composition of the depot fat of cattle. AB - The influence of liveweight, total carcass fat and the amount of fat at five specific anatomical locations on the fatty acid composition of the depot fat of adult ruminants was examined. The total carcassfat and the amount offat at specific locations seem to affect the fatty acid composition significantly. No important significant correlation between liveweight and fatty acid composition was found. There was an increase in odd, even and branched chain fatty acids, and a decrease in linoleic acid, with increase in animal age. PMID- 22055344 TI - Autophagy proteins regulate the secretory component of osteoclastic bone resorption. AB - Osteoclasts resorb bone via the ruffled border, whose complex folds are generated by secretory lysosome fusion with bone-apposed plasma membrane. Lysosomal fusion with the plasmalemma results in acidification of the resorptive microenvironment and release of CatK to digest the organic matrix of bone. The means by which secretory lysosomes are directed to fuse with the ruffled border are enigmatic. We show that proteins essential for autophagy, including Atg5, Atg7, Atg4B, and LC3, are important for generating the osteoclast ruffled border, the secretory function of osteoclasts, and bone resorption in vitro and in vivo. Further, Rab7, which is required for osteoclast function, localizes to the ruffled border in an Atg5-dependent manner. Thus, autophagy proteins participate in polarized secretion of lysosomal contents into the extracellular space by directing lysosomes to fuse with the plasma membrane. These findings are in keeping with a putative link between autophagy genes and human skeletal homeostasis. PMID- 22055347 TI - Dendritic growth of ice crystals during the freezing of beef. AB - The morphology adopted by ice in frozen tissues is accepted as one of the factors responsible for freezing damage. For this reason ice nucleation and growing mechanisms have been extensively studied. However, under the conditions used in the industry, where important temperature gradients exist, the classical analysis of nucleation and growth, depending on the supercooling, is complicated by the dendritic growth of crystals as well as by the possibility of the location of the ice crystal inside or outside the cells. In the present paper experiments which verify the existence of dendritic ice growth during the freezing of beef are described. The dendritic growth rate of ice in beef is measured as a function of the supercooling and an analysis of the expected mechanism, according to freezing conditions, is also provided. PMID- 22055348 TI - Variation in the carcass characteristics of commercial british sheep with particular reference to overfatness. AB - Classification records for 136,000 sheep carcasses, a1 in 20 sample of those classified by the Meat and Livestock Commission in 1977, were used to examine the variation in weight, fatness and conformation of commercial British sheep. Overall mean carcass weight was 17.4 kg. Mean subcutaneous fat percentage in carcass (SF(e)) was estimated from the distribution of carcasses between fat classifications. Overall SF(e) was 11.3% and the regression of SF(e) on carcass weight was 0.44 %/kg. There were important differences in the characteristics of carcasses from abattoirs in different regions of the country: carcass weights ranged from 15.5 kg (Wales) to 23.4 kg (north of Scotland). Lambs slaughtered in the north of Scotland were also fattest (mean SF(e) = 13.9). The classification records were used together with results from MLC dissection studies to estimate excess fat production nationally. On the assumption that the consumer eats five parts lean to one part fat, excess carcass fat production from lambs and hoggets in 1977 was estimated to be 25,000 t. PMID- 22055349 TI - Vacuum-packaging of bovine edible offal. AB - Edible offals are relatively perishable and may be frozen before leaving the abattoir, commanding a lower price on the wholesale market than fresh offals. Investigations are described in which a range of offals was vacuum-packaged in an effort to extend the shelf-life of the fresh material. Several visits to two abattoirs revealed that their offals after chilling were generally of rather poor microbiological quality, partly due to handling practices and, in one abattoir, to inadequate chilling. Reductions in the initial microbial load on hearts and tongues were achieved by immersion in water at 90 degrees C, or with 100 ppm free chlorine or 1 % (v/v) lactic acid. However, these treatments offered no advantage over good production methods in extending the safe storage period in the vacuum package. When offals produced under normal conditions were vacuum-packaged a storage period of 2-3 weeks at 1 degrees C +/- 1 degrees was achieved which allowed a subsequent shelf-life of 3-4 days in air at 4 degrees C. Offals produced with low initial numbers of contaminants gave the possibility of 1-2 weeks longer in the vacuum-package. A detailed investigation of the organisms growing on vacuum-packaged liver showed that a lactic flora developed during storage, but this did not inhibit potential spoilage organisms such as Pseudomonas or Alteromonas. PMID- 22055350 TI - Carbon-13 pulsed fourier transform nuclear magnetic resonance spectroscopic determination of 4-hydroxy-l-proline in meat-comparison with the colorimetric method. AB - The 4-hydroxy-l-proline content of a variety of meats and meat products was determined both by carbon-13 pulsed Fourier transform nuclear magnetic resonance (FTNMR) spectroscopy and by a traditional colorimetric method. These two fundamentally different methods gave results which were in good agreement; both methods require chemically free 4-hydroxy-l-proline from hydrolysis which is the time-consuming experimental step. The relative merits are discussed with reference to specifity, operator time and sample throughput. Observation of 4 hydroxy-l-proline without time-consuming hydrolysis by (13)C-FTNMR spectroscopy was found to be possible with collagen and with carbohydrate-free meat samples. Direct observation without such hydrolysis could be useful as a rapid survey method if carbohydrate interferences can be eliminated. PMID- 22055351 TI - Colour determination of beef juices as an indicator of beef cooking temperatures. AB - Dominant wavelengths and other colour parameters of beef juices were investigated as predictors of maximum internal temperatures attained during beef cooking since beef imported by the USA from South American countries has to be cooked to a temperature compatible with the inactivation of the foot-and-mouth disease virus. Although the correlation between these parameters was highly significant, the prediction error was high and similar in magnitude to that obtained with other methods. However, according to the results obtained, a method was devised to evaluate if beef has been cooked to at least 79.4 degrees C. Basically, the method consists in the visual comparison of the juice with a liquid standard of certain spectral characteristics. This method is simple and reliable for use at the port of entry or at the manufacturing plant. In doubtful cases the instrumental method described could be used to ascertain whether a certain temperature had been attained. PMID- 22055352 TI - Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epilepsy. AB - Valproic acid (VPA) is a well-established anticonvulsant drug that has been increasingly used in the treatment of many forms of generalized epilepsy. Although there are many reports of adverse effects of VPA, studies focusing on the concentration-response relationships of VPA and its metabolites in patients with epilepsy are extremely limited. In this study, a rapid and specific high performance liquid chromatography-ultraviolet (HPLC-UV) method to simultaneously detect the concentrations of VPA and its major hepatotoxic metabolite 2-propyl-4 pentenoic acid (4-ene VPA) in human plasma has been established, using 2,4' dibromoacetophenone and octanoic acid as the derivatization reagent and internal standard, respectively. This method was used to analyze plasma samples (n=64) of Chinese patients with epilepsy. The results revealed that 4-ene VPA concentrations in Chinese patients were much higher than those in patients in other countries such as United States and Iran. Significant correlations between aspartate aminotransferase (AST), alanine aminotransferase (ALT) and 4-ene VPA concentration suggest that the simultaneous determination of VPA and 4-ene VPA is an effective tool for the prediction of clinical hepatotoxicity in epileptic patients. Furthermore, the present study describes a less costly and complex technique for the clinical monitoring of VPA plasma levels and the risk of hepatotoxicity which may be of particular interest in developing countries like China. PMID- 22055353 TI - Independent predictors and a prognostic model for surgical outcome in refractory frontal lobe epilepsy. AB - PURPOSE: Refractory frontal lobe epilepsy (FLE) remains one of the most challenging surgically remediable epilepsy syndromes. Nevertheless, definition of independent predictors and predictive models of postsurgical seizure outcome remains poorly explored in FLE. METHODS: We retrospectively analyzed data from 70 consecutive patients with refractory FLE submitted to surgical treatment at our center from July 1994 to December 2006. Univariate results were submitted to logistic regression models and Cox proportional hazards regression to identify isolated risk factors for poor surgical results and to construct predictive models for surgical outcome in FLE. RESULTS: From 70 patients submitted to surgery, 45 patients (64%) had favorable outcome and 37 (47%) became seizure free. Isolated risk factors for poor surgical outcome are expressed in hazard ratio (H.R.) and were time of epilepsy (H.R.=4.2; 95% C.I.=1.5-11.7; p=0.006), ictal EEG recruiting rhythm (H.R.=2.9; 95% C.I.=1.1-7.7; p=0.033); normal MRI (H.R.=4.8; 95% C.I.=1.4-16.6; p=0.012), and MRI with lesion involving eloquent cortex (H.R.=3.8; 95% C.I.=1.2-12.0; p=0.021). Based on these variables and using a logistic regression model we constructed a model that correctly predicted long term surgical outcome in up to 80% of patients. CONCLUSION: Among independent risk factors for postsurgical seizure outcome, epilepsy duration is a potentially modifiable factor that could impact surgical outcome in FLE. Early diagnosis, presence of an MRI lesion not involving eloquent cortex, and ictal EEG without recruited rhythm independently predicted favorable outcome in this series. PMID- 22055354 TI - From depressive symptoms to depression in people with epilepsy: contribution of physical exercise to improve this picture. AB - OBJECTIVES: Epilepsy is a chronic condition that may be associated with several other diseases. Psychiatric comorbidities are highly prevalent and depression is the most common type of psychiatric comorbidity in people with epilepsy. The beneficial effects of exercise for people with epilepsy have been increasingly reported, including reduction of seizure susceptibility, improvement of quality of life and reduction of depression. In this regard, we propose in this article the potential role of physical exercise to minimize depression in people with epilepsy. METHODS AND RESULTS: We summarized the most relevant data on the complex relationship between neurotransmitters and epilepsy, depression, physical exercise and subsequently proposed how a regular program of exercise can regulate depression associated with epilepsy. CONCLUSIONS: The significance of such a relationship has a marked impact on the development and implementation of appropriate coadjutant treatments to improve functional outcomes and quality of life in people with epilepsy. PMID- 22055355 TI - Systems biology impact on antiepileptic drug discovery. AB - Systems biology (SB), a recent trend in bioscience research to consider the complex interactions in biological systems from a holistic perspective, sees the disease as a disturbed network of interactions, rather than alteration of single molecular component(s). SB-relying network pharmacology replaces the prevailing focus on specific drug-receptor interaction and the corollary of rational drug design of "magic bullets", by the search for multi-target drugs that would act on biological networks as "magic shotguns". Epilepsy being a multi-factorial, polygenic and dynamic pathology, SB approach appears particularly fit and promising for antiepileptic drug (AED) discovery. In fact, long before the advent of SB, AED discovery already involved some SB-like elements. A reported SB project aimed to find out new drug targets in epilepsy relies on a relational database that integrates clinical information, recordings from deep electrodes and 3D-brain imagery with histology and molecular biology data on modified expression of specific genes in the brain regions displaying spontaneous epileptic activity. Since hitting a single target does not treat complex diseases, a proper pharmacological promiscuity might impart on an AED the merit of being multi-potent. However, multi-target drug discovery entails the complicated task of optimizing multiple activities of compounds, while having to balance drug-like properties and to control unwanted effects. Specific design tools for this new approach in drug discovery barely emerge, but computational methods making reliable in silico predictions of poly-pharmacology did appear, and their progress might be quite rapid. The current move away from reductionism into network pharmacology allows expecting that a proper integration of the intrinsic complexity of epileptic pathology in AED discovery might result in literally anti-epileptic drugs. PMID- 22055356 TI - Antioxidative activity of alpha-tocopherol in cooked and uncooked ground pork. AB - The effect of alpha-tocopherol (0, 100, 200 ppm) on lipid oxidation either in cooked or uncooked ground pork was studied during aerobic storage at 4 degrees C and -20 degrees C. Lipid oxidation was measured using the 2-thiobarbituric acid (TBA) method and rancidity development was scored by a trained sensory panel. Alpha-tocopherol slowed the rate of oxidation in cooked ground pork stored at either 4 degrees C or -20 degrees C and uncooked samples refrigerated for extended periods of time (12 days). In cooked product stored at 4 degrees C where oxidation development was intense and off-flavors were strong, panelists did not detect flavor differences due to treatments. But in cooked product stored at -20 degrees C sensory results were consistent with TBA analysis. Pre-rigor grinding, known to induce a high pH and inhibit lipid oxidation in uncooked fresh pork, had no protective effect on lipid oxidation as measured by TBA values in cooked ground pork, regardless of storage condition. TBA numbers increased during storage of cooked product at 4 degrees C with an increase in internal cooking temperature between 50 degrees C and 80 degrees C. Internal cooking temperatures of 70 degrees C or higher induced a rapid rate of oxidation when stored at 4 degrees C. PMID- 22055357 TI - A preliminary study of the effect of urea in the preservation of meat. AB - An investigation was undertaken on the effect of urea in the preservation of meat. It was observed that there was always a lag period in the early stages of microbial spoilage of meats at different temperatures, due to the non availability of required nutrients, and subsequent rapid growth of microorganisms was attributed to the utilisation of amino acids released due to autolytic changes. Dry urea salt was employed in the present study to denature or retard the activity of enzymes of the meat in order to extend the shelflife of meat by preventing spoilage. Parameters such as ERV, pH and TPC were studied during meat spoilage. It appears from the present studies that autolytic changes were responsible for the ultimate spoilage of meat. When urea was applied in the meat, the microbial lag phase and the shelflife of meat were extended. It seems that urea checked the autolytic changes in meat and thereby microbial growth was delayed due to the non-availability of nutrients from the autolytic changes. PMID- 22055358 TI - The effect of electrical stunning and slaughter on the electroencephalogram of sheep and calves. AB - To study the application of electroencephalography (EEG) for the assessment of insensibility during stunning and slaughter, recordings were made on sheep that were slaughtered by throat cutting, electrically stunned head-only and allowed to recover, electrically stunned head-only followed by throat cutting or electrically stunned head-to-back. The same experiments were repeated on calves (1-6 weeks old) except some calves were stunned and allowed to recover before final stunning and throat cutting. After the throat cut, sheep became insensible (i.e. EEG < 10 MUV) at 8-22 s but the calf EEG did not fall below 10 MUV until 79 s after the cut. With head-only stunning/recovery, high-amplitude EEG waves (electroplectic fit) continued for 47 s (sheep) and 33 s (calves) post stun. A quiescent period followed, which then developed into a period of moderate amplitude EEG signals, so that, at 50 s post stun, the EEG usually exceeded 50 MUV and often had bursts of 150 MUV activity. After head-only stunning/throat cutting, the electroplectic fit was shortened (39 s in sheep, 23 s in calves) and the EEG took at least 50 s to fall below 10 MUV. With sheep stunned head-to-back, which stops the heart, and thus should cause immediate, permanent insensibility, the EEG took longer to fall below 10 MUV (52 s) than after throat cutting. These results suggest that electrical stunning of sheep and calves causes a prolonged increase in the post-stun EEG amplitude. Therefore, during slaughter, stunned animals have larger amplitude EEG signals than unstunned animals, and EEG criteria developed for judging the sensibility of unstunned animals cannot be used for those that are electrically stunned. PMID- 22055359 TI - Effect of breed-type on the relationships between intramuscular and total body fat in steers. AB - The partitioning of total dissectible body fat and the amounts of intramuscular fat in Psoas major, Semitendinosus and Biceps brachii muscles were determined in two groups of A. Angus and AA * Nelore steers with similar averages of total dissectible fat (27.7 kg). In addition, the fatty acid composition of total fat and the triglyceride fraction from dissectible and intramuscular fats were determined. The AA * Nelore steers have higher levels of subcutaneous fat and lower levels of intermuscular fat than the A. Angus but contain lower levels of intramuscular fat in the three muscles. The allometric regressions varied according to the muscle and breed type. The fatty acid composition of subcutaneous and kidney fats were similar but differences in the percentages of 14:0, 18:0, 18:2 and 20:4 fatty acids in intramuscular fats between the two genetic groups were detected. PMID- 22055360 TI - Elastin in bovine Semitendinosus and Longissimus dorsi muscles. AB - The structural organization of elastin present in bovine semitendinosus and longissimus dorsi muscles was examined using light and scanning electron microscopy. Qualitatively, both muscles were found to have the same organization of the two structural forms of elastin present. Coarse elastin fibres (5-10 MUm diameter) were found in the epimysium and perimysium, aligned with the long axis of the muscle fibres. In addition, finer elastin fibres (1-2 MUm diameter) were found in the epimysial and perimysial sheets of collagen. These finer elastin fibres approximated the course of the collagen fibres, i.e. at an angle to the muscle fibre long axis. Quantitatively, the semitendinosus muscle epimysium and perimysium contained very heavy deposits of the coarse elastin fibres and nearly every sheet of perimysium, even the thinest, contained the fine elastin fibres. By comparison, less of the coarse elastin was present in the longissimus dorsi epimysium and it was quite rare in the perimysium. The finer elastin fibres were, however, reasonably common. The significance of this structural arrangement is discussed in relation to muscle function and to meat toughness assessment. PMID- 22055363 TI - The use of ultrasound to predict fatness in lambs. AB - Ultrasonic measurement of fat depth, over the eye muscle of lambs was found to be highly correlated with measurement on the carcass in two experiments with coefficients of 0.93 and 0.95. Linear regression analysis showed that over a limited range of fatness the slope (regression coefficient) approached unity and the residual standard deviation of the regression was approximately +/- 1 mm. However, the slope of the line was greater than unity over a wider range of fatness and the accuracy decreased. The instrument used was more useful for predicting fat depth than carcass fat percentage, explaining less of the variation in the latter variable than the former. It is apparent that further investigation of the instrument over a wide range of lambs is needed to clarify the implications for selection schemes or, alternatively, technology adopted which overcomes the underestimation found in fat animals. PMID- 22055364 TI - Chemical composition and quality of camel meat. AB - L. dorsi, Semitendinosus and Triceps brachii muscles from the camel had similar moisture, protein and fat content, but significantly (P < 0.05) different ash content. These muscles had also similar sarcoplasmic and myofibrillar protein concentrations. L. dorsi muscle had the highest content of collagen but a higher solubility of hydroxyproline than Semitendinosus and Triceps brachii muscles. It also had a brighter red colour. Water-holding capacity was not significantly different between the three muscles studied. Shear force and connective tissue strength were lowest in L. dorsi, intermediate in Semitendinosus and highest in Triceps brachii. PMID- 22055365 TI - The amount and composition of the proteins in drip from stored pig meat. AB - In order to elucidate the mechanism of drip formation, measurements have been made of the amount of drip, and its protein concentration, from 80 pigs chilled conventionally. The correlation between amount of drip and protein concentration was poor but significant (r = -0.41, P < 0.001). The individual protein components of 20 drip samples were analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Relative protein composition varied with amount of drip. As the amount of drip increased above about 12% the absolute amounts of some proteins decreased; these proteins were creatine kinase and/or phosphoglycerate kinase (under the system used, these two proteins comigrate and therefore cannot be distinguished), myokinase, and an unidentified protein of molecular weight 137000. Drip contained similar proteins to a sarcoplasmic extract and in similar amounts. These results show that drip is mainly sarcoplasmic in origin and we suggest that the systematic changes in individual proteins as the amount of drip increases may be explained by denaturation of some or all of these proteins and possibly by dilution with fluid from within the myofibril. PMID- 22055366 TI - The effects of differences in inherent muscle quality and frozen storage on the flavor and texture profiles of pork loin roasts. AB - Complete flavor and texture profiles on pork loins from 118 carcasses revealed the following findings: (1) freezing, storing and thawing pork loins produced a slight tenderizing effect by making them less cohesive and easier to chew; permitted greater moisture release during chewing, thereby, slightly increasing the juiciness; resulted in a breakdown to more appropriate residual particles which resulted in a more appropriate, well balanced and blended texture; but resulted in a less appropriate and well balanced flavor; (2) pork with normal muscle quality had a firmer, more elastic, and cohesive texture which was stringier, more fibrous, and harder to compress, resulting in a slower breakdown to particles which tended to be fibrous, grainy and mealy; (3) the PSE condition appeared to result in a drier texture with less moisture and fat being released during mastication and a greater amount of moisture being absorbed from the mouth; (4) the DFD condition appeared to result in a juicier texture with greater amounts of fat and moisture being released into the mouth during mastication and a softer texture which was less cohesive, fibrous, and stringy and easier to chew, but as the DFD condition became extreme the texture became excessively soft, crumbly and mushy resulting in a relatively large proportion of small mealy and/or mushy particles which detracted from the texture amplitude; (5) the PSE condition resulted in a predominance of sour notes which detracted from the flavor amplitude, and possibly resulted from more extensive accumulation of lactic acid during postmortem glycolysis; and (6) the DFD condition resulted in a predominance of porky, sweet, and fatty character notes which enhanced the flavor amplitude but as the DFD condition became extreme, more character notes contributing to off-flavors were detected, a portion of which were apparently due to sex taint. Present findings clearly document the influence of differences in inherent muscle quality on palatability properties of pork loins and aid in resolving the controversy that presently exists within the literature regarding the effects of freezing, frozen storage, and thawing on pork palatability. However, further research will be required to document the impact of such influences on consumer acceptance. PMID- 22055367 TI - Characteristics of pork products from Swine Fed a high monounsaturated fat diet: Part 1-Whole muscle products. AB - Twelve percent of high-oleic sunflower oil (HOSO) was incorporated into a swine diet to replace substantial amounts of saturated fatty acids (S) in pork by monounsaturated fatty acids (M). Pork loin chops (longissimus dorsi), cooked to 74 degrees C, and eye of round roasts (semitendinosus), cooked to 77 degrees C, from animals on the HOSO diet were 49% and 66%, respectively, higher in the M S ratio as compared to their counterparts from animals on the control diet. Cooking had little effect on relative differences in the M S ratio between HOSO and control samples. Cooking loss and sensory properties were not adversely affected by the changes in fatty acid composition. However, cooked chops and roasts from the HOSO group had lower thiobarbituric acid values during storage at 4 degrees C. PMID- 22055368 TI - Characteristics of pork products from swine fed a high monounsaturated fat diet: Part 2-Uncured processed products. AB - The effects of incorporation of 12% high-oleic sunflower (HOSO; >85% in oleic acid) into a swine diet on properties of uncured, processed pork products were determined. Restructured pork chops (with an initial total-fat level of <5%) and ground pork patties (with targeted initial total-fat levels of 15% and 30%) processed from animals fed the HOSO diet, when compared to the corresponding products from animals fed the control diet without HOSO, were 28% and 38%, respectively, lower (0.72 and 0.62 fold, respectively) in the proportion of total saturated fatty acids; 25% higher (1.25 fold) in the proportion of total monounsaturated fatty acids for both products; and 73% and 105%, respectively, higher in the ratio of monounsaturated to saturated fatty acids (M S ). The M S ratio differences were not significantly changed by cooking. Cooking loss for either restructured chops or ground pork patties was similar between the product from animals on the control diet and that from animals on the HOSO diet. When restructured chops were evaluated for sensory properties, HOSO and control samples were similar in all sensory attributes evaluated for broiled chops while HOSO samples were juicier for precooked-reheated chops. Thiobarbituric acid (TBA) values were not significantly different between HOSO and control samples for stored, restructured chops; for pork patties, differences between the diet treatment groups were dependent on whether patties were stored raw or cooked. PMID- 22055371 TI - Understanding the child's world of work. PMID- 22055372 TI - Care of infants and children with bronchiolitis: a systematic review. AB - Bronchiolitis is the most frequent cause of hospitalization in the infant population. Management varies widely, and the efficacy of many routinely implemented therapies is not supported by evidence. The purpose of the systematic review was to identify the best evidence available regarding the care of infants and children with bronchiolitis. A two-phase literature search was performed, and 20 publications were appraised. An abundance of evidence regarding management of bronchiolitis was revealed resulting in numerous recommendations. Use of a clinical pathway is proposed as a possible solution for moving this evidence into practice. PMID- 22055373 TI - Examining factors that increase and decrease stress in adolescent community college students. AB - In contrast to adolescents attending traditional universities, adolescents attending community colleges represent a large but relatively unstudied population with respect to stress and mental health issues. The purpose of this study was to determine what factors increase and decrease stress in a sample of adolescent community college students (N = 166). Findings from a self administered questionnaire indicated that students had moderate levels of stress and resilience. Contrary to predictions, males demonstrated statistically significant higher levels of stress than females, but as expected, resilience had a significant negative effect on stress (p < .05). Practice and research implications are discussed for nurses in pediatric settings. PMID- 22055374 TI - Testing guidelines for child health care nurses to prevent nonsynostotic plagiocephaly: a Swedish pilot study. AB - The aim of the study is to test effectiveness of guidelines for nurses that can be incorporated into the child health care program to prevent nonsynostotic plagiocephaly (NSP) in infants while still following sudden infant death syndrome preventive recommendations. When guidelines were followed as intended in a Swedish pilot study, only 8.5% of infants had some degree of NSP at 6 months, compared to 25.6% of infants in the comparison group. Results indicate that the early and regular implementation of these guidelines by nurses may be an effective way to prevent NSP. PMID- 22055375 TI - Making education count: the nurse's role in asthma education using a medical home model of care. AB - Asthma care for patients who have limited health literacy is very costly. The resources to help patients who have lower health literacy levels are very few are not well identified. Significant gains in asthma control, self-efficacy in managing asthma, and improvement in overall costs of care for this patient population can be achieved when health literacy challenges are addressed. This research suggests that one-on-one education with an asthma educator that specifically addresses health literacy levels and care designed around the National Asthma Guidelines can produce significant reductions in the cost for asthma care through decreased emergency department visits and hospitalizations, and improved self-management of asthma exacerbations. PMID- 22055376 TI - Item selection in self-report measures for children and adolescents with disabilities: lessons from cognitive interviews. AB - The aim of the study was to evaluate children's and adolescents' understanding of items from self-report measures. Cognitive interviews were conducted as part of a larger study on pain and fatigue in children with disabilities. A list of guiding questions was used to encourage participants to talk about words or concepts in the scale that they found difficult. The sample included 32 children and adolescents with physical disabilities. Participants had difficulty with words such as intense, severe, and anxiety. They had more difficulty with abstract ideas, such as average, than they did with more concrete ideas, such as naming a recreational or social activity. Because poor outcome measurement hinders symptom evaluation, findings support the need to put greater emphasis on the child perspective when developing and using self-report measures. Suggestions for increasing accuracy of these measures are offered for clinicians and researchers. PMID- 22055377 TI - Using the Braden Q Scale to Predict Pressure Ulcer Risk in pediatric patients. AB - The Braden Q Scale for Predicting Pediatric Pressure Ulcer Risk (Braden Q Scale) is a widely used, valid, and reliable pediatric-specific pressure ulcer risk assessment tool. Since its original publication, requests for clarification on how best to use the tool across the wide spectrum of pediatric patients commonly cared for in health care systems have been received. Common clarifications focus on using the Braden Q Scale as originally designed; specifically, not using untested derivations of the tool, and not using the Braden Q Scale to predict medical device-related pressure damage. The purpose of this article is to provide practical information on how best to use the Braden Q Scale and how to score a pediatric patient's risk for pressure ulcers. Accurate assessment of patient risk for pressure ulcers is the first step in guiding appropriate nursing interventions that prevent pressure ulcers. Patient assessment, scoring, and common clinical scenarios are presented. PMID- 22055378 TI - Unique children in unique places: innovative pediatric community clinical. AB - Pediatric nursing is a specialization that requires a particular set of skills and abilities. Most nurses seldom get the chance to interact with families who have children living with exceptionalities unless they choose to work in tertiary settings dealing exclusively with children. This article explores how one school of nursing in Canada offers its students two unique learning opportunities where they get the chance to work with children who have special needs in an interdisciplinary community-based setting. Shared statements from parents and students highlight the benefits to all those involved. PMID- 22055379 TI - Developing a robust professional practice model using a shared governance approach. AB - This article describes the development and implementation of a framework for nursing practice in a freestanding children's hospital and the subsequent improvement process used to transition that framework into a robust professional practice model (PPM). The development of a PPM encompassing all aspects of nursing in all clinical settings is an important milestone on a successful Magnet journey. Strategies for linking the PPM to core processes and structures of nursing are shared. Plans for further study to demonstrate the relationship of a PPM to patient outcomes are discussed. PMID- 22055380 TI - Children and disaster planning: national commission findings. PMID- 22055381 TI - Preparing pediatric nurses for the 21st century: perceptions of nurse managers, nursing faculty, and staff nurses. PMID- 22055382 TI - Sleep-wake patterns of school-age children and adolescents before diagnosis and during induction chemotherapy for acute lymphocytic leukemia. AB - Sleep disturbances are commonly reported by children receiving chemotherapy for leukemia. Sleep patterns before diagnosis and during induction chemotherapy were evaluated in 38 children (7 to 18 years old). Child Sleep Assessment (CSA) was used to evaluate sleep patterns prior to diagnosis. Sleep diaries and actigraphy were used during chemotherapy. Adolescents went to bed later and awakened later than school-age children before diagnosis and during chemotherapy. During chemotherapy, children averaged 60 minutes of nighttime wake time. The early recognition of sleep problems associated with disease, treatment, and age is important for school-age children and adolescents with leukemia. PMID- 22055383 TI - Testing the theory of reasoned action in explaining sexual behavior among African American young teen girls. AB - This study tested the Theory of Reasoned Action to examine the prediction of early sexual behavior among African American young teen girls. Baseline data from a longitudinal randomized clinical trial were used. Between 2001 and 2005, 198 middle-school girls aged 11 to 14 years were recruited. As girls aged, they held more permissive attitudes toward engaging in early sexual behavior and had a higher intention to engage in early sexual behavior. Intention was a significant predictor to explain sexual behavior among the girls. There is a need to develop strategies that promote intention related to delay and prevention of early sexual behavior. PMID- 22055384 TI - Caregiver knowledge and self-confidence of stress dosing of hydrocortisone in children with congenital adrenal hyperplasia. AB - Congenital adrenal hyperplasia (CAH) is a rare disorder characterized by cortisol deficiency, with/without aldosterone deficiency, and androgen excess. The purposes of this descriptive, exploratory study were to assess caregiver knowledge of CAH, adrenal crisis, and stress dosing of hydrocortisone during times of acute illness and to assess caregivers' self-efficacy in managing adrenal crisis and stress dosing of children with CAH. A survey was distributed that collected information about child and family demographics and about caregiver knowledge of the disorder and stress dosing instruction history and evaluated their self-efficacy. Caregivers of children with CAH (N = 60) have a solid knowledge base of the disorder and maintain a reasonably high degree of self-efficacy of stress dosing. Although most that were surveyed currently had a filled prescription for injectible hydrocortisone, less than 40% received the prescription at the time of their child's diagnosis. Only 70% surveyed had received a written guideline sheet outlining proper stress dosing procedure, and only half of them received an injection technique demonstration. Caregivers who received written instruction and demonstration of injection technique scored significantly higher in self-efficacy for managing adrenal crisis and the injection procedure. PMID- 22055385 TI - A biopsychosocial pilot study of overweight youth and care providers' perceptions of quality of life. AB - This pilot study examined the relationship between youth and care provider self reports of depressive symptoms assessed through the Patient Health Questionnaire and reports of youth physical and psychosocial functioning assessed by PedsQL4.0 in a rural outpatient overweight pediatric population (N = 66 child and care provider pairs). The relationship between youth body mass index (BMI), youth and care provider depression, youth quality of life (QOL), care provider perception of youth QOL, and youth and care provider congruence of QOL perceptions was examined. Paired t tests were completed to assess the differences between QOL scores for youth and care providers for subgroups based on age, age and gender, and age and race. The mean age of youth participants was 11.9 years; youth BMI ranged from 26.76 to 54.10 (M = 37.20). Our results showed that there are significant differences in youth and care providers' perceptions of QOL when specific demographic categories are assessed by age, gender, and race. PMID- 22055386 TI - Provision of smoke-free homes and vehicles for kindergarten children: associated factors. AB - Many children continue to be exposed to environmental tobacco smoke (ETS) each day. To describe the factors associated with providing a smoke-free home (PSFH) and vehicle (PSFV) for kindergarten children, a cross-sectional descriptive study was conducted in Manitoba, Canada, with 551 mothers and primary caregivers responding. A social-ecologic model of health behavior guided the study. In the bivariate analysis, being better educated, living with a partner, and having a higher income were associated with PSFH. In the multivariable logistic regression analysis, the variables most predictive for PSFH were living with a partner and the mother's self-efficacy, and for PSFV, the most predictive variables were the mother's self-efficacy and ETS knowledge. Smoking behaviors are complex and must be considered broadly within all levels of influence if nurses are to assist parents in protecting their children. PMID- 22055388 TI - Comment on: Postprandial hypertriglyceridemia predicts improvement in insulin resistance in obese patients after bariatric surgery. PMID- 22055387 TI - Optogenetic tools for analyzing the neural circuits of behavior. AB - In order to understand how the brain generates behaviors, it is important to be able to determine how neural circuits work together to perform computations. Because neural circuits are made of a great diversity of cell types, it is critical to be able to analyze how these different kinds of cell work together. In recent years, a toolbox of fully genetically encoded molecules has emerged that, when expressed in specific neurons, enables the electrical activity of the targeted neurons to be controlled in a temporally precise fashion by pulses of light. We describe this optogenetic toolbox, how it can be used to analyze neural circuits in the brain and how optogenetics is impacting the study of cognition. PMID- 22055389 TI - Duration of surgery independently influences risk of venous thromboembolism after laparoscopic bariatric surgery. AB - BACKGROUND: Obesity is a recognized risk factor for venous thromboembolism (VTE). The aims of the present study were to determine the risk factors for symptomatic VTE in morbidly obese patients undergoing laparoscopic bariatric surgery. METHODS: This was a retrospective study that included consecutive patients who had undergone bariatric surgery from January 2007 to May 2010. Thromboprophylaxis included routine application of low-molecular-weight heparin, pneumatic calf compression, and early ambulation. Extensive measures, such as temporary insertion of a caval filter (n = 5) and anticoagulation (n = 11), were used in selected higher risk patients. The patients were followed up for a minimum of 3 months after surgery to determine the incidence of clinical VTE. The results are presented as the mean and range. RESULTS: A total of 500 consecutive patients aged 44.7 years (range 19-77) with a body mass index of 49.2 kg/m(2) (range 32.1 84.3) underwent laparoscopic bariatric surgery (442 gastric bypass, 20 sleeve gastrectomy, and 38 gastric banding). No conversions to open surgery occurred, and the operative time, morbidity rate, and mortality rate was 93.7 minutes (range 20-325), 2.8%, and .2%, respectively. No clinical deep vein thrombosis was encountered, although 3 patients (.6%) developed pulmonary embolism. Cox regression multivariate analysis identified the operative time as the only independent predictor of postoperative VTE (relative risk .0002 per min, P = .009). Multivariate analysis identified the body mass index as an independent predictor of the operating time. CONCLUSION: Increasing obesity was associated with a longer operative time, which consequently increased the risk of VTE. PMID- 22055390 TI - Influence of pouch and stoma size on weight loss after gastric bypass. AB - BACKGROUND: Enlargement of the gastric pouch and/or gastrojejunostomy after Roux en-Y gastric bypass (RYGB) is postulated to be the antecedent to suboptimal weight loss or weight regain. The present study evaluated the gastric pouch and stoma dimensions in RYGB patients and correlated them with the weight loss outcomes. METHODS: Patients who underwent upper endoscopy for investigation of gastrointestinal symptoms or weight regain after RYGB were identified. The stoma was considered enlarged if >2 cm in diameter and the pouch was considered enlarged if >6 cm long or >5 cm wide. Successful weight loss was defined as excess weight loss >50% or a body mass index decrease to <= 30 kg/m(2). RESULTS: A total of 380 patients had nondiagnostic upper endoscopy findings at a mean post RYGB interval of 5.9 +/- 4.0 years. Among these were 175 patients (group A; 87% women) who had successful weight loss and 205 patients (group B; 86% women) who were referred for investigation of weight regain. The pouch and stoma size were normal in most of the patients in group A (63.4%) compared with 28.8% of the patients in group B (P <.001). The most common abnormality was an enlarged stoma. The pouch length, pouch volume, and stoma diameter correlated inversely with excess weight loss. Multivariate analysis identified that the stoma diameter was independently associated with weight regain after RYGB. CONCLUSION: The current definition of a "normal" size pouch/stoma is associated with optimal weight loss after RYGB, although this might need to be reviewed. Patients who regain weight are likely to have abnormal anatomy, in particular, stoma enlargement. The surgical RYGB technique and methods of evaluating the gastric anatomy in RYGB patients need to be standardized, intraoperatively and postoperatively. PMID- 22055391 TI - A snapshot of chemoresistance to PARP inhibitors. AB - The exploitation of synthetic lethality in BRCA-deficient tumor carriers using potent inhibitors of the enzyme poly(ADP-ribose) polymerase (PARP)-1 has led to an enthusiastic response among basic scientists, oncologists and pharmaceutical companies. However, accumulating evidence demonstrates that resistance to these drugs develops in tumors in both preclinical and clinical settings. Here, I focus on literature dealing with resistance to these drugs and discuss the molecular mechanisms involved, such as restoration of BRCA function, upregulation of nonhomologous end-joining-dependent DNA repair, induction of P-glycoprotein expression and epigenetic deregulation. Clinical implications of resistance to PARP1 inhibitors are also discussed. PMID- 22055392 TI - Apoptosis in the anucleate platelet. AB - For many years, programmed cell death, known as apoptosis, was attributed exclusively to nucleated cells. Currently, however, apoptosis is also well documented in anucleate platelets. This review describes extrinsic and intrinsic pathways of apoptosis in nucleated cells and in platelets, platelet apoptosis induced by multiple chemical stimuli and shear stresses, markers of platelet apoptosis, mitochodrial control of platelet apoptosis, and apoptosis mediated by platelet surface receptors PAR-1, GPIIbIIIa and GPIbalpha. In addition, this review presents data on platelet apoptosis provoked by aging of platelets in vitro during platelet storage, platelet apoptosis in pathological settings in humans and animal models, and inhibition of platelet apoptosis by cyclosporin A, intravenous immunoglobulin and GPIIbIIIa antagonist drugs. PMID- 22055394 TI - Mycobacterium mucogenicum and other non-tuberculous mycobacteria in potable water of a trauma hospital: a potential source for human infection. AB - This study examined the frequency of occurrence of non-tuberculous mycobacteria (NTM) in potable water samples from a main trauma hospital in Mexico City. Sixty nine potable water samples were collected, 23 from each source: cistern, kitchen tap and bathroom showers. Of the 69 samples, 36 harboured NTM species. Twenty nine of the 36 isolates were Mycobacterium mucogenicum, two Mycobacterium rhodesiae, one Mycobacterium peregrinum, one Mycobacterium fortuitum and three were Mycobacterium spp. Hospital potable water harbouring NTM represents a potential source for nosocomial infections, therefore we suggest that hospital potable water microbiological guidelines should include testing for NTM species. PMID- 22055395 TI - Acute post-traumatic stress in survivors of critical illness who were mechanically ventilated: a mixed methods study. AB - This study investigated the severity of post-traumatic stress (PTS) symptoms, the relationships between PTS symptoms and clinical and demographic characteristics and the subjective experiences of patients who were critically ill and mechanically ventilated in intensive care. Study participants (n=97) completed the Impact of Event Scale (IES) to assess avoidance and intrusive symptoms of PTS within one week of hospital discharge. A subset (n=5) with IES scores suggestive of symptoms of PTS participated in semistructured interviews analysed with content analysis. Participants had a mean age of 57.73 years, 40% were female and median duration of ventilation was 90.98 hours. The mean IES score was 20.34. Scores >25 were reported by 37% and were associated with younger age (p<0.05) in bivariate analysis; multiple linear regression showed no independent associations with IES scores. The interviews revealed distorted perception and gaps in memory of ICU, fear of recurrence of illness, avoidance of usual activities and sleeping problems as common. In conclusion, high levels of symptoms of PTS were present in one-third of ICU survivors. There were no independent relationships between PTS and patient characteristics studied. Experiences of interviewees with high distress scores were consistent with those reported in other studies of ICU survivors. PMID- 22055396 TI - Exploring the influence of enforcing infection control directives on the risk of developing healthcare associated infections in the intensive care unit: a retrospective study. AB - BACKGROUND: Although strict adherence to infection control strategies is recognised as the simplest and most cost effective method to prevent the spread of healthcare associated infections (HAIs), measurement of the direct impact that such adherence may have on the risk of developing such infections has always been a challenge. PURPOSE: The purpose of this study was to compare the risk of HAIs before and during the SARS outbreak. Such comparison is intended to provide a surrogate measure of the influence that strict enforcement of infection control strategies during the SARS outbreak may have had on the risk of HAIs. METHODS: A retrospective chart review was conducted on the medical records of 400 intensive care patients who were admitted to the ICU three months before and during the 2003 SARS outbreak. RESULTS: The rate of HAIs was higher in the pre-SARS period than the SARS period. Specifically, 61.7% of all reported infections were diagnosed in the pre-SARS period. The rate of HAIs in the pre-SARS period was 14.5% as opposed to 9% during the SARS period. Adjusted logistic regression analysis suggested that the odds of HAIs were 2.2 times higher in the pre-SARS period as compared to the SARS period (OR=2.2; 95%CI=1.08-4.49). CONCLUSION: Our findings suggest that strict enforcement of infection control strategies may have a positive impact on the efforts to minimise the risk of HAIs. These findings carry a clinical significance that shall not be ignored with regard to our overall efforts to minimise the risk of developing HAIs in the ICU. PMID- 22055397 TI - Serious complications in connection with cardiac surgery--next of kin's views on information and support. AB - OBJECTIVE: Next of kin (NoK) to patients undergoing cardiac surgery expect successful outcomes but sometimes serious complications occur and this affects their NoK. To describe NoK's experiences of information and support when serious complications occur during the first 30 days after cardiac surgery. METHODS: A qualitative, critical incident technique was used. Forty-two NoK were asked to describe their experiences of information and support. RESULTS: Three main areas emerged from the analysis. The first main area, Confidence during the waiting period, described how NoK could not participate in the forthcoming operation and how the NoK were informed. The second main area, Involvement during the hospital stay, described how the NoK feel trust in the healthcare professionals and dissatisfaction with the care in relation to the operation. The third main area, Sense of abandonment, described problems with the rehabilitation. CONCLUSIONS: These findings show the importance of pre- and post operative contacts between healthcare professionals, patients and NoK. When the NoK and the patients are well informed it constitutes a basis for fruitful conversations between them and the healthcare professionals, and everyone can be better prepared if complications occur. PMID- 22055398 TI - Anaplastic thymic carcinoma: a clinicopathologic and immunohistochemical study of 6 cases. AB - Primary thymic anaplastic ("undifferentiated") carcinoma is an unusual thymic neoplasm that, to date, has not been properly characterized. We present 6 such cases in an attempt to better define this entity. The patients were 5 women and 1 man with an age range from 42 to 72 years (mean, 62 years). None of the patients had any history or radiologic evidence of tumor elsewhere. All patients presented with symptoms related to their anterior mediastinal masses: shortness of breath, chest pain, and cough. Histologically, the lesions were characterized by infiltrative tumors with marked cytologic atypia, bizarre tumor giant cells, and atypical mitoses. None of the neoplasms showed areas of other well-defined types of thymic carcinoma. Immunohistochemically, all tumors showed positive staining for pancytokeratin, 40% expressed Pax8, and none reacted with thyroid transcription factor 1 or beta-human chorionic gonadotropin. Follow-up available for 4 patients showed that 3 patients had died 14, 22, and 63 months after diagnosis, whereas 1 patient is alive 4 months after diagnosis. Two patients were lost to follow-up. Anaplastic thymic carcinoma is a distinct morphological type of thymic carcinoma with an aggressive clinical course, which needs to be included in the differential diagnosis of tumors displaying giant cells in the anterior mediastinum. PMID- 22055399 TI - Total Survivin and acetylated Survivin correlate with distinct molecular subtypes of breast cancer. AB - Global gene expression profiling studies led to the recent classification of breast cancer into 4 distinct molecular subtypes including luminal, human epidermal growth factor receptor 2 enriched, basal like, and unclassified. Here, we used immunohistochemistry to evaluate expression of the antiapoptotic protein Survivin and its recently described acetylated form, Survivin acetyl129, in normal breast tissue and in 226 primary breast tumors of different molecular subtypes. Correlation of Survivin expression with molecular markers and its impact on patient outcomes were analyzed. Eighty-four percent of basal-like tumors expressed high levels of total Survivin, whereas 52% of luminal tumors expressed high levels of acetylated Survivin (P < .001). Overall survival (91%) for tumors expressing low levels of total Survivin was better than that for tumors expressing high levels of total Survivin (72%, P = .02), whereas the reverse was true for tumors expressing acetylated Survivin. In hierarchical cluster analysis, total Survivin clustered with basal marker expression, whereas acetylated Survivin clustered with luminal marker expression. In multivariate analysis, high total Survivin expression was an independent predictor of worse overall survival in patients with breast cancer (relative risk, 11; P < .01). These data indicate that high levels of total Survivin predict poor outcome in patients with grade 3 invasive ductal carcinoma and correlate directly with a basal-like phenotype. In contrast, high expression of the acetylated form of the protein associates with a favorable outcome and preferentially correlates with luminal-type tumors. Survivin likely has different functions in distinct breast cancer subtypes, and diagnostic strategies that incorporate immunohistochemical markers that detect both Survivin forms may help better strategize patient risk and direct therapy. PMID- 22055400 TI - Pancreatic acinar-like adenocarcinoma of the proximal stomach invading the esophagus. AB - The aim of this study was to systematically investigate clinicopathologic features of the recently described pancreatic acinar-like adenocarcinoma of the proximal stomach invading the esophagus (n = 43). Patient median age was 66 years (range, 51-90 years). The male-to-female ratio was 7.6. Grossly, pancreatic acinar-like adenocarcinoma tumors were nonencapsulated with the median size of 5.5 cm (range, 2-10.5). Bormann's types 1 to 4 tumors were in 7%, 9%, 67%, and 16% cases, respectively. Frank necrosis, hemorrhage, and cysts were rare or absent. Lymphovascular (81%), perineural (74%), and lymph node (81%) invasions were more common in the pancreatic acinar-like adenocarcinoma than in the non pancreatic acinar-like adenocarcinoma (n = 94) groups. Microscopically, pancreatic acinar-like adenocarcinoma tumors showed acinar (78%), micropapillary (12%), microcystic, solid, trabecular, and mixed neuroendocrine or signet ring (33%) patterns of growth. No adenosquamous differentiation was noted in the pancreatic acinar-like adenocarcinoma group. Nuclei were round to oval with thickened nuclear membrane, stippled chromatin, and single prominent nucleoli. Mitotic figures were variable. The cytoplasm was moderate, eosinophilic, finely granular, and diffusely immunoreactive to the alpha1-chymotrypsin antibody in all cases to various degrees. Tumor stroma was nondesmoplastic, delicate, and fibrovascular. Pancreatic acinar-like adenocarcinoma tumors staged pI, pII, pIII, and pIV were in 2%, 21%, 70%, and 7% of cases, respectively. The median number of follow-up months after surgery was 29. The 2-year survival rate was 67%, lower than that (73%) in the non-pancreatic acinar-like adenocarcinoma group. A worse overall survival trend was found for patients in the pancreatic acinar-like adenocarcinoma than in non-pancreatic acinar-like adenocarcinoma groups, but the difference was not statistically significant. Age older than 75 years and overall pathology stage were independent risk factors. PMID- 22055401 TI - Inhibin-alpha and synaptophysin immunoreactivity in synovial sarcoma with granular cell features. AB - We recognized immunoreactivity for the alpha subset of inhibin and synaptophysin in synovial sarcomas with granular cell features. Histologic findings of 90 cases of synovial sarcoma were reviewed. Two (2.2%) of the 90 cases had granular cell features, showing sheet or nested proliferation of characteristic epithelioid cells with abundant eosinophilic and granular cytoplasm, in addition to the typical spindle cell component. The 2 cases were both female (aged 86 and 76 years). The tumors were located in the foot and the retroperitoneum and measured 3.5 and 14 cm in maximum diameter. Reverse transcriptase polymerase chain reaction analysis revealed SS18-SSX1 transcripts in both cases. SS18 gene rearrangement was detected in granular cells as well as spindle cells by chromogenic in situ hybridization. Immunohistochemistry found the granular cells to be positive for inhibin-alpha in both cases and for synaptophysin in 1 case, whereas spindle cells were not. Thirty-six cases (20 monophasic fibrous, 11 biphasic, and 5 poorly differentiated synovial sarcomas) were additionally examined for comparison; they showed no immunoreactivity for inhibin-alpha or synaptophysin. This is the first report of immunoreactivity for inhibin-alpha and synaptophysin in synovial sarcoma. These immunohistochemical findings might be characteristic of synovial sarcomas with granular cell features. PMID- 22055402 TI - Post-mortem electrical stimulation and high temperature ageing of hot-deboned beef. AB - The effects of electrical stimulation (80-100 V, 15 pps) of hot-deboned, bovine Longissimus dorsi muscles, followed by ageing at 30 degrees or 40 degrees Cfor 5, 7 or 10 h, on the solubility of sarcoplasmic and myofibrillar proteins, soluble non-protein nitrogen, and on the water-holding capacity, colour, tenderness and microbiological status of the meat, was assessed. Comparisons were made with the same traits measured on non-stimulated controls (average muscle temperature, 5 degrees C), which were cold-deboned post rigor, and with hot deboned, electrically stimulated muscles, subsequently held at 2 degrees C. For each treatment and its corresponding control, six muscles each were studied. Such electrical stimulation produced a typical acceleration of pH fall post mortem and enhanced ageing changes at both 30 degrees C and 40 degrees C. It significantly increased tenderness over non-stimulated, cold-deboned controls. The higher temperature of ageing, however, was significantly associated with adverse colour development, loss of water-holding capacity and increased microbial growth. Electrical stimulation alone would not obviate the need for immediate refrigeration in hot-deboning operations with ambient temperatures of ~ 40 degrees C. PMID- 22055403 TI - Prediction of the weight of lean and fat yield in bacon weight carcasses. A comparison of predictors used in commercial pig carcass classification. AB - Alternative methods of pig carcass description were compared as predictors of the weight (kg) of commercial lean yield and fat yield in 209 bacon weight carcasses. The predictors used included hot carcass weight and carcass sex in association with: the backfat measurements used in the Danish grading scheme (minimum loin, 3rd-4th lumbar and 3rd-4th last rib fat thickness); the proposed Australian system (P(2) fat thickness); fat classes published by the South Australian Livestock Marketing Study Group (1980); mid-line carcass measurements (backfat at minimum loin, mid back, maximum shoulder as well as carcass length) and visual carcass grade. There was no difference in precision between the carcass classification systems as predictors of lean yield. (R(2) = 69.0 % and residual standard deviation = 1.5.) Precision varied between the predictors of fat yield. The predictors were ranked as follows with R(2)(%) and residual standard deviation in parentheses. Danish (80.0, 0.50); Australian (70.5, 0.60); fat class (67.8, 0.64); mid-line (64.9, 0.67) and grade (58.1, 0.72). PMID- 22055404 TI - A comparison of the optical intrascope, the Hennessy & Chong Fat Depth Indicator and the Danish MFA probe to predict pig carcass backfat thickness. AB - Two automatic backfat measurement devices (the New Zealand Hennessy & Chong Fat Depth Indicator (FDI) and the Danish Meat Fat Automatic (MFA) probe) were compared with the Optical Intrascope (OI) as alternative devices to predict P(2) backfat thickness (65 mm from the dorsal mid-line at the level of the posterior edge of the head of the last rib) in pig carcass classification schemes. Prediction equations of P(2) backfat thickness (mm) taken on the cold carcass (cold P(2)) were developed for two operators who made independent hot carcass P(2) measurements (hot P(2)) with the O1, FDI and MFA on each of 114 carcasses. The OI and FDI were found to be of equivalent precision in predicting cold P(2) with the same operator (residual standard deviation, RSD = 1.29 and 1.30, respectively). The MFA was significantly (P < 0.05) less precise (RSD = 1.81). Between operator measurements of hot P(2) with the FDI (RSD = 1.17) had significantly (P < 0.05) less variation compared with the OI and MFA (RSD = 1.27). PMID- 22055405 TI - Energy substrate provision in vivo and the changes in muscle pH post mortem. AB - The effects of alpha- and of beta-adrenergic stimulation (both with and without concurrent blockade of lipolysis) on energy substrate provision in vivo, and the subsequent changes in muscle metabolism post mortem, were studied in sheep. Treatment with the alpha-agonist phenylephrine had no effect upon plasma glycerol, free fatty acids, glucose or lactate levels or on muscle metabolism post mortem. Concurrent treatment with an inhibitor of lipolysis, methyl pyrazole carboxylic acid (MPCA), caused a reduction in plasma free fatty acids and glycerol and some decrease in muscle glycogen levels at slaughter. Administration of the beta-agonist, isoproterenol, stimulated an increase in plasma levels of all the energy substrates measured and caused a marked increase in liver glycogen and a decrease in muscle glycogen at slaughter, but no dark cutting. However, when energy from fat depots was blocked by MPCA during beta-stimulation, muscle glycogen was almost exhausted at slaughter and dark cutting was found in all the carcasses. From these experiments it is concluded that dark cutting meat does not result solely from increased adrenergic stimulation, but is dependent upon the availability of energy substrates from muscle, liver and fat energy stores. PMID- 22055406 TI - Caffeine stimulated lipolysis protects pigs against catecholamine-induced dark cutting. AB - High ultimate pH dark cutting meat was obtained in Pietrain pigs following overnight intravenous infusion of the beta-adrenergic agonist, isoproterenol. This effect was enhanced by simultaneous administration of the antilipolytic agent nicotinic acid and completely reversed by pretreatment of the animals with caffeine (which stimulates lipolysis). These results suggest that the availability of energy substrates from adipose tissue (free fatty acids and glycerol) is an important factor in the production of dark cutting meat. Stimulation of lipolysis in animals prior to pre-slaughter stresses (such as transport and lairing) could possibly reduce the incidence of dark cutting meat. PMID- 22055407 TI - Effect of high pressure on the regulation of phosphorylase activity in pre-rigor rabbit muscle. AB - The effects of high pressure (150 MPa) on the regulation of phosphorylase activity in pre-rigor rabbit muscles have been studied at 35 degrees and 0 degrees C. At 35 degrees C muscle contracts, phosphorylase is activated and the muscle pH falls to 5.8 in 2 min. Coinciding with these changes, phosphorylase phosphatase activity falls rapidly, while phosphorylase kinase, although active for longer, loses its activity as the pH falls. Both of these enzymes are completely inactivated after 5 min under pressure, while phosphorylase still retains 80% of its activity under these conditions. The effects of pressure on the activities of these enzymes in white and red muscles of rabbits were compared, with a greater effect being observed in white muscles. At 0 degrees C, muscles subjected to high pressure did not contract, but at this temperature the three enzyme activities (phosphorylase, phosphorylase kinase and phosphorylase phosphatase) were all lost at a greater rate than at 35 degrees C, although the pH of the muscle did not fall below 6.5. The effects of high pressure treatment on isolated phosphorylase a and b and phosphorylase kinase were also studied at both 0 degrees and 35 degrees C and the results obtained closely paralleled those observed in whole muscle. PMID- 22055408 TI - Conformationally restricted analogs of the direct thrombin inhibitor FM 19. AB - The serine protease thrombin plays several key roles in the clotting cascade within the hemostatic system, such as in fibrin formation and platelet activation. Thus, development of an inhibitor that binds to the enzyme's active site (a direct thrombin inhibitor) offers an approach for the treatment of thrombus-associated diseases. Previous structure-activity relationship studies originally based on the bradykinin breakdown product Arg-Pro-Pro-Gly-Phe (RPPGF) led to the development of lead compound FM 19 (d-Arg-Oic-Pro-d-Ala-Phe(p-Me) NH(2)). The recently determined X-ray structure of FM 19 in the active site of thrombin has revealed sites of modification to potentially improve inhibition. In this study, we report the synthesis and biological characterization of nine peptides that replace only the d-Arg residue of the FM 19 sequence, investigating ways to add conformational restriction, modification of the basic moiety at the end of the side chain, and removal of the charge from the N-terminus. Two of these peptides, 6 and 7 (IC(50) values of 0.51 and 0.45 MUM, respectively), show similar potency to the best compounds in the FM 19 series reported thus far. PMID- 22055409 TI - Physico-chemical and organoleptic properties of patties from hot, chilled and frozen goat meat. AB - The effects of processing hot versus chilled goat meat, as such and after freezing in chunk or mince forms, were studied in relation to physico-chemical and organoleptic properties of patties. The differences in the pH of the meat samples were non-significant (P < 0.05) at 3-4 h post mortem (PM) at room temperature (30 degrees C) and after 24 h at 4 degrees C. The yield of the broiled patties, prepared from hot meat at 3-4 h PM, was significantly lower (P<0.05) as compared to those from chilled meat. However, this trend was reversed, if processing of hot meat into patties was done within 1-2 h PM. Freezing of chilled meat in chunk or mince forms gave significantly higher (P < 0.05) cooking yields than freezing of hot meat in similar forms. The organoleptic scores of the raw-cooked patties were similar for all treatments. Freezing of precooked patties at -10 degrees C for 10 days, thawing and reheating did not reduce most of the sensory scores significantly (P<0.05). Moisture, protein and fat contents of the broiled patties were not significantly (P<0.05) affected by the treatments. Standard plate count of hot versus chilled meat, for all levels of processing and storage, were within acceptable limits. PMID- 22055410 TI - The comparison of electroencephalograms recorded before and after electrical stunning of cattle. AB - Electroencephalograms (EEGs) were recorded before and after 'head-only' electrical stunning of adult cattle. Epochs of 8.5 s duration derived from the pre-and the post-stun EEG signals were compared for differences in scale and frequency. The frequency structures of two selected epochs from the one animal were evaluated using the periodogram ordinates derived by calculating the Fast Fourier Transform. The comparison of the two pre-stun epochs indicated that, within the one animal, the pre-stun EEG signal had a consistent frequency pattern. Similarly, a comparison of two post-stun epochs indicated that the post stun EEG signal also had a consistent frequency pattern. The comparison of pre- and post-stun epochs indicated a consistent increases in amplitude after stunning. Additionally, after stunning, there was an increase in the power of frequencies in the range 4-8 Hz and a decrease in the power of certain frequencies in the range 15-25 Hz. Although there was considerable animal-to animal variation it was demonstrated that electric stunning produced definable changes in the EEG signal. PMID- 22055411 TI - Influence of packaging method and length of chilled storage on microflora, tenderness and colour stability of venison loins. AB - Sections of venison loins (LD) weighing approximately 300 g from 12 red deer (Cervus elaphus) were packaged using four packaging methods: (a) vacuum packaging, (b) CO(2) flushed using a nylon containment film (CO(2)-Nylon), (c) CO(2) flushed using an ultra-high barrier containment film (CO(2)-UHB), and (d) CO(2) flushed using an aluminium foil laminate containment film (CO(2)-Foil) and stored for 1, 6, 12 and 18 weeks at 0 degrees C. Meat pH values were lower in all CO(2) flushed meat packages (P<0.05) than in vacuum packaged meat. Lactic acid bacteria and total anaerobic counts increased over storage time in all packages regardless of treatment up to values of log(10) 7.8 and 7.6 g(-1), respectively. Tenderness tended to increase as meat was stored for up to 18 weeks. Colour scores taken during simulated retail display indicated that colour deteriorated more rapidly when meat was stored for 12 and 18 weeks than for 1 and 6 weeks. Vacuum packaging and gas flushing (CO(2)-Foil) resulted in higher initial colour scores than venison packaged in the CO(2)-Nylon or CO(2)-UHB materials. Venison stored for 18 weeks also exhibited a higher proportion of packages containing off odours, lower flavour desirability and flavour intensity scores as well as higher off flavour scores than meat stored for shorter times. The implications of these effects are discussed. Although there were few significant differences in microbial growth and sensory characteristics due to packaging method or containment film, vacuum packaging appeared to be the most economic and produced meat of better colour stability. PMID- 22055412 TI - Effect of light and packaging conditions on the colour stability of sliced ham. AB - The colour fading of sliced ham displayed in chill cabinets has been found to be caused by the combined action of light and oxygen, and can be prevented by a combination of packaging in a plastic material with low oxygen transmission rate (OTR<4 cm(3)/m(2)/24h/atm), a high initial vacuum level (>99%), and cold storage in the dark until residual oxygen in the packaging has been consumed (4 days for >99% initial vacuum). UV-light permeability of the packaging material had no effect on colour stability. The colour was measured by tristimulus colorimetric measurements on the surface of ham packaged in packaging material with different OTR (60 and <4 cm(3)/m(2)/24h/atm) and UV-light permeability (transparent above 360 and above 250 nm), and the change in colour was monitored by the Hunter a value, the tristimulus colorimetry parameter found (by analysis of variance) to give the best correlation with the subjectively evaluated ham colour. For each of the four types of packaging material, three different initial vacuum levels (85, 95 and >99%) were used. PMID- 22055413 TI - The actin content of different muscles from beef and pork. AB - In the literature 3-methylhistidine (3-MeHis) is mentioned as a parameter for the determination of meat content. Because of the variable molar ratio of 3-MeHis in the myofibrillar protein myosin, this indicator cannot be used without some restriction. However, the content of 3-MeHis in the myofibrillar protein actin is constant. Moreover, actin is relatively heat-stable in comparison with other muscle proteins. These facts made actin an interesting parameter for determination of the meat (protein) content of heated and raw meat products. Fast protein liquid chromatography (FPLC) was used to separate from a meat extract an actin-containing fraction without myosin. The actin content of the meat was calculated from its content in the fraction. The latter was determined by means of a 3-MeHis method. Several muscles of the beef and pig carcass were examined for their actin contents. Generally, the actin values were comparable with the data reported in the literature. The influence of heat treatment was also studied on one type of beef muscle. The determined actin content was not affected up to a temperature of 85 degrees C. PMID- 22055414 TI - Actin-bound 3-methylhistidine as an index of myofibrillar protein in food. AB - An improved method for determining the actin-bound 3-methylhistidine titre of muscle is described. Using this procedure, the titres of actin-bound 3 methylhistidine in bovine muscles Longissimus dorsi (loin), Masseter and Malaris (cheek) and Semimembranosus (round), could be accurately determined and were found to be similar to one another. Actin-bound 3-methylhistidine is thus suggested as an even more consistent index of meat protein than is total protein bound 3-methylhistidine, since the 3-methylhistidine titre is low in the myosins of ruminant Masseter and Malaris muscles. PMID- 22055415 TI - Effect of packaging and display variables on retail display of frozen lamb chops. AB - Display conditions of packaging and lighting and the length of frozen storage of the carcass before cutting were examined for their effect on the colour of frozen chops during display. Lighting effected a greying and loss of saturation of the colour, while packaging film affected brightness and hue angle. Length of storage affected hue and saturation. Display time affected brightness and hue in a linear manner. PMID- 22055416 TI - Chemical effects of smoke processing on frankfurter quality and palatability characteristics. AB - Frankfurters were made by standard commercial practices except for the smoke treatment which involved four different methods: solid smoke-aerosol, liquid smoke-aerosol, liquid smoke-external dip and liquid smoke-internal mix. For control purposes, frankfurters were prepared without any smoke treatment. All frankfurters were packaged and stored at 5 degrees C with samples removed for analyses weekly for three weeks. All smoke-processing treatments resulted in products assessed as overall acceptable with the experienced sensory panel unable to detect differences among the various methods of manufacture except for the franks made by mixing liquid smoke in the emulsion. However, the flavour scores of those products subjected to external smoke-processing treatments were higher and more acceptable than the other two treatments. Frankfurters manufactured using aerosol smoke treatments were rated by sensory panellists as the most tender. However, shear force measurements indicated that those franks processed with external liquid smoke treatments were somewhat less tender. Liquid smoke processing techniques favoured the development of a more desirable cured colour. The most stable colour was attributed to the liquid smoke-processing system in which the smoke materials were mixed in the emulsion. All palatability properties (sensory and colour) were highly correlated with the smokiness of the product. Generally, storage time had little effect on frankfurter palatability characteristics. PMID- 22055417 TI - Instability of SDS-denatured proteins prepared from musle myofibrils. AB - Evidence is presented showing that myofibrils solubilised by sodium dodecyl sulphate undergo proteolysis upon being allowed to warm to room temperature overnight or on storage for several days at 0-4 degrees C. Results indicate that the extra protein bands occurring under such conditions are due to the presence of an indigenous muscle protease(s). Modifications in the handling of samples are suggested in order to avoid these artifacts. The possible significance of the protease(s) to meat tenderness is briefly discussed. PMID- 22055418 TI - The influence of age, sex and breed of cattle on their muscle characteristics. AB - In order to gain more knowledge of the systematic changes occurring in meat tenderness and colour of different breeds and sexes of growing cattle, a number of characteristics were studied in five different muscles of Afrikaner and Friesland bulls and steers between birth and 24 months of age. Muscle collagen content of bulls was higher at birth than at all other ages and solubility of collagen decreased markedly between birth and 16 months of age. Shear force increased between 8 and 16 months, partially coinciding with the decrease in collagen solubility. Collagen content of muscles was higher in bulls than in steers and solubility decreased markedly between 12 and 16 months, only in the case of bulls. Afrikaner muscles were more tender than those of Frieslands and had a higher content and solubility of collagen. Pigment content was higher in Afrikaner than in Friesland muscles and increased steadily with age in all animals. The results show that the biological differences found to influence muscle characteristics were particularly those of age and breed of animal. PMID- 22055419 TI - Adrenal ascorbic acid depletion as an index of preslaughter stress in pigs. AB - The weight of the adrenal glands and the amount of ascorbic acid they contained were measured in Large White pigs subjected to various preslaughter treatments. Compared with transport for four hours preslaughter, one hour's transport resulted in adrenal glands which weighed less and which contained less ascorbic acid. Pigs mixed with strange pigs in lairage had heavier adrenals containing more ascorbic acid than those of unmixed pigs. Increasing lairage time up to twenty-four hours raised both the concentration and total amounts of ascorbic acid in the adrenal glands. The results suggest that the depletion of ascorbic acid from the adrenal glands can be used as a measure of the stress experienced by animals during the preslaughter period and the extent to which resting in lairage allows them to recover. PMID- 22055420 TI - Effects of calcium and pH on spun fibres produced from plasma-alginate mixtures. AB - When a solution of blood plasma and sodium alginate (protein: polysaccharide ratio 3:1) was extruded into coagulating baths of calcium chloride there was a rapid increase in shear strength of the fibre bundles with a rise in salt concentration up to 3% calcium chloride. Above this concentration no further increase in shear strength was observed. The ratio of plasma protein to alginate was between 0.84 and 1.1 in all tows produced from unbuffered calcium chloride baths. Extruding the dope into 5% calcium chloride baths of pH values between 2 and 8 indicated that fibre strength was independent of pH in the range 4 to 8. Below pH 4 the tows rapidly decreased in shear strength to a minimum at pH 3.5. Decreasing the pH further led to an increase in fibre strength as acid denaturated protein coprecipitated with the polysaccharide. The ratio of plasma to alginate in the tows was around 1.0 for pH values above 3.5, rapidly increasing to 2.8 at pH 2.0. PMID- 22055421 TI - Evaluation of plasma and plasma-alginate fibres for use in sausages. AB - Fresh beef sausages were made in which 0,20 or 40% of the meat protein was replaced by protein from bovine blood plasma in order to determine the effect this had on stability, shrinkage, texture, juiciness, flavour, colour and general acceptability. Both the plasma proteins as isolated, and after spinning into fibres, were examined. Sausages in which 20 or 40% of the meat protein had been replaced by plasma-alginate fibres were preferred less than those made at the same levels of replacement using plasma protein as isolated, taste panel members disliking their flavour and colour. On the other hand, sausages incorporating plasma-alginate fibres were drier than those containing corresponding replacement levels of plasma protein as isolated, and their texture was preferred. PMID- 22055422 TI - Mercury, chromium, lead and organochlorine pesticide residues in some food products of animal origin: A review. AB - The authors present the results of several years' work in the field of food pollution. The research, which has been carried out on food products of animal origin marketed in the north of Italy, has established that the degree of contamination by heavy metals (mercury, chromium and lead) and organochlorine pesticides is generally lower than the tolerances suggested by the World Health Organisation. PMID- 22055423 TI - A consumer test of bull and steer beef of equal fatness. AB - It has been suggested that differing fatness may be a major contribution to detected eating differences between bull and steer beef. This paper compares a subset of households who cooked and ate bull and steer beef of equal fatness. Respondents still detected that steer was preferable to bull. PMID- 22055424 TI - Association between life events and change in depressive symptoms in Hong Kong Chinese elderly. AB - BACKGROUND: Life event was regarded as an important risk factor for depression. Only a few prospective studies had examined the impact of life events individually and in combination. This study examined the relationship between life events and change in depressive symptoms. METHODS: Depressive symptoms were assessed longitudinally using Geriatric Depression Scale (GDS) in 2630 community dwelling Chinese elderly aged 65 or above. A cutoff score of 8 or higher indicated clinically relevant depressive symptoms. Subjects identified as demented were excluded. Eight life events experienced in the past year were assessed at 2year follow up. Logistic regression analyses were performed with adjustments for baseline GDS score and potential confounders such as sociodemographic, developmental and social factors, alcohol consumption, medical history and physical health status. RESULTS: In men, experience of two events (OR=2.493) and three or more events (OR=3.199) was independently associated with increased risk of having depression. In women, the risk increased only in experiencing three or more events (OR=5.558). Moreover, life event affected depressive symptoms differently for men and women. Loss of pet and serious financial trouble were associated with an increase in depressive symptoms among men, but serious illness or accident of partner, and loss of a hobby were significant among women. Experience in either good or bad important events increased risk of depression in both sexes. LIMITATIONS: The main limitation was all subjects were ambulatory volunteers. CONCLUSIONS: The occurrence of single life event had contributed to the onset of depression and multiple events had a cumulative effect. PMID- 22055425 TI - Twelve-month prevalence and correlates of subthreshold and threshold anxiety in community-dwelling older adults with cardiovascular diseases. AB - BACKGROUND: Studies that examined the prevalence of anxiety in older adults with cardiovascular diseases (CVD) were mainly conducted in clinical settings limiting the generalizability of the results to community-based samples. Moreover, among older adults with CVD, little is known about the prevalence of subthreshold anxiety and about which characteristics differentiate those with subthreshold anxiety from those having an anxiety disorder. This study aimed at determining the 12-month prevalence rates of subthreshold and threshold anxiety in community dwelling older adults with CVD as well as to examine whether older people with CVD reporting an anxiety disorder differ from their counterparts with subthreshold anxiety. METHOD: From a representative sample of community-dwelling older adults aged 65years and older (N=2811), 613 cases of CVD were identified based on government medical records. Subthreshold and threshold anxiety were assessed using in-home interviews based on the DSM-IV criteria. RESULTS: The 12 month prevalence rates of anxiety disorders and subthreshold anxiety were, respectively, 5.1 and 14.8%. Compared to older adults with CVD reporting no anxiety, individuals reporting subthreshold or threshold anxiety are more likely to be women, to have high blood pressure, and to suffer from a depression. LIMITATIONS: No information was gathered regarding alcohol and tobacco use. CONCLUSIONS: The present study provides evidence for the fact that subthreshold anxiety has a high prevalence among community-dwelling older people with CVD and that clinicians working with this population should screen for anxiety, even at a subthreshold level, since it may be associated with high blood pressure and depression. PMID- 22055426 TI - In vivo determination of the Achilles tendon moment arm in three-dimensions. AB - Two-dimensional methods have been applied to determine the Achilles tendon moment arm in previous studies, although the talocrural joint rotates in three dimension. The purpose of this study was to develop a method for determining the Achilles tendon moment arm in three-dimensions (3DMA). A series of sagittal ankle images were obtained at ankle positions of -20 degrees , -10 degrees (dorsiflexed position), 0 degrees (neutral position), +10 degrees , +20 degrees , and +30 degrees (plantarflexed position). The talocrural joint axis was determined as the finite helical axis of the ankle joint over 20 degrees of displacement, and the 3DMA was determined as the shortest distance from the talocrural joint axis to the line of action of the Achilles tendon force. The corresponding 2DMA was determined with the center of rotation method using the images captured on the sagittal plane passing through the mid-point of the medio lateral width of the tibia. The 3DMA ranged from 35 to 41 mm across various ankle positions and was, on average, 11 mm smaller than 2DMA. The difference between the two measures was attributable primarily to the deviations of the talocrural joint axis from the anatomical medio-lateral direction. The deviations on the coronal plane (21.4+/-20.7 degrees ) and on the transverse planes (14.8+/-22.6 degrees ) accounted for the errors of 1.3 mm and 3.0 mm, respectively. In addition, selecting either a medially or laterally misaligned sagittal-plane image for determining the 2DMA gave rise to error by 3.5 mm. The remaining difference was accounted for by the random measurement error. PMID- 22055427 TI - 3D real-time micromechanical compressive behaviour of bone-cement interface: experimental and finite element studies. AB - The integrity of bone-cement interface is essential for the long-term stability of cemented total joint arthroplasty. Although several studies have been carried out on bone-cement interface at continuum level, micromechanics of the interface has been studied only recently for tensile and shear loading cases. Fundamental studies of bone-cement interface at microstructural level are critical to the understanding of the failure processes of the interface, where multiple factors may contribute to failure. Here we present a micromechanical study of bone-cement interface under compression, which utilised in situ mechanical testing, time lapsed microcomputed tomography (CT) and finite element (FE) modelling. Bovine trabecular bone was used to interdigitate with bone cement to obtain bone-cement interface samples, which were tested in step-wise compression using a custom-made loading stage within the MUCT chamber. A finite element model was built from the CT images of one of the tested samples and loaded similarly as in the experiment. The simulated stress-displacement response fell within the range of the experimental responses, and the predicted local strain distribution correlated well with the failure pattern in the subject-specific experimental model. Damage evolution with load in the samples was monitored both experimentally and numerically. The results from the FE simulations further revealed the development of damage in the regions of interest during compression, which may be useful towards a micromechanics understanding of the failure processes at bone-cement interface. PMID- 22055428 TI - The relationships between cyclic fatigue loading, changes in initial mechanical properties, and the in vivo temporal mechanical response of the rat patellar tendon. AB - Damage accumulation underlies tendinopathy. Animal models of overuse injuries do not typically control loads applied to the tendon. Our in vivo model in the rat patellar tendon allows direct control of the loading applied to the tendon. Despite this advantage, natural variation among tendons results in different amounts of damage induced by the same loading protocol. Our objectives were to (1) assess changes in the initial mechanical parameters (hysteresis, stiffness of the loading and unloading load-displacement curves, and elongation) after fatigue loading to identify parameters that are indicative of the induced damage, and (2) evaluate the relationships between these identified initial damage indices with the stiffness 7 day after loading. Left patellar tendons of adult, female retired breeder, Sprague-Dawley rats (n = 68) were fatigue loaded per our previously published in vivo fatigue loading protocol. To induce a range of damage, fatigue loading consisted of either 5, 100, 500 or 7200 cycles that ranged from 1 N to 40 N. Diagnostic tests were applied before and immediately after fatigue loading, and after 45 min of recovery to deduce recoverable and non-recoverable changes in initial damage indices. Relationships between these initial damage indices and the 7-day stiffness (at sacrifice) were determined. Day-0 hysteresis, loading and unloading stiffness exhibited cycle-dependent changes. Initial hysteresis loss correlated with the 7-day stiffness. k-means cluster analysis demonstrated a relationship between 7-day stiffness and day-0 hysteresis and unloading stiffness. This analysis also separated samples that exhibited low from high damage in response to both high or low number of cycles; a key delineation for interpretation of the biological response in future studies. Identifying initial parameters that reflect the induced damage is critical since the ability of the tendon to repair depends on the damage induced and the number of applied loading cycles. PMID- 22055429 TI - The role of skin texture and facial shape in representations of age and identity. AB - Faces have both shape and skin texture, but the relative importance of the two in face representations is unclear. Our goals were first, to determine the contribution of shape versus texture to aftereffects for facial age and identity and second, to assess whether adaptation transferred between shape and texture, suggesting integration in a single representation. In our first experiment we examined age aftereffects. We obtained young and old images of two celebrities and created hybrid images, one combining the structure of the old face with the skin texture of the young face, the other combining the young structure with the old skin texture. This allowed us to create adaptation contrasts where the two adapting faces had the same facial structure but different skin texture, and vice versa. In the second experiment, we performed a similar study but this time examining identity aftereffects between two people of a similar age. We found that both skin texture and facial shape generated significant age aftereffects, but the contribution was greater from texture than from shape. Both texture and shape also generated significant identity aftereffects, but the contribution was greater from shape than from texture. In the last experiment, we used the normal and hybrid images to determine if adaptation to one property (i.e., texture) could create aftereffects in the perception of age in the other property (i.e., shape). While there was significant within-component adaptation for texture and shape, there was no evidence of cross-component adaptation. We conclude that shape and texture contribute differently to different face representations, with texture dominating for age. The lack of cross-component adaptation transfer suggests independent encoding of shape and texture, at least for age representations. PMID- 22055430 TI - [Are there any contraindications to the transradial approach?]. AB - The transradial approach is the most frequent access used in France for coronarography and percutaneous coronary intervention. This access permits a reduction of local complications in comparison with femoral access. There are very few real contraindications of transradial approach. The use of Allen's test before coronarography remains controversial in the transradial catheterization community. It remains a standard practice in some institutions, however many centers have stopped using Allen's test considering that there is no evidence supporting its use. PMID- 22055431 TI - [Variant angina: what to think in 2011?]. AB - Spastic angina is considered rare but its prevalence is probably underestimated especially in case of atherosclerotic coronary lesions. Its diagnosis remains important due to its poor prognosis and therapeutic characteristics. We report three clinical cases illustrating two different clinical presentations and the problem of diagnosis of spastic angina. We performed a review of the literature essentially concerning commonly used diagnosis means and especially provocative testing for coronary spasm. This test needs to be adapted to the evolution of techniques and uses of coronary angiography in 2011, particularly the wide spread use of radial approach. Therefore new recommendations are needed, specifying the terms of provocative testing and establishing clear diagnosis criteria including clinical, electrocardiographic and angiographic data. Such guidelines would probably help to better diagnose and treat these patients in our practice. PMID- 22055432 TI - The role of MAPK in CD4(+) T cells toll-like receptor 9-mediated signaling following HHV-6 infection. AB - Human herpesvirus-6 (HHV-6) is an important immunosuppressive and immunomodulatory virus that primarily infects immune cells (mainly CD4(+) T cells) and strongly suppresses the proliferation of infected cells. Toll-like receptors are pattern-recognition receptors essential for the development of an appropriate innate immune defense against infection. To understand the role of CD4(+) T cells in the innate response to HHV-6 infection and the involvement of TLRs, we used an in vitro infection model and observed that the infection of CD4(+) T cells resulted in the activation of JNK/SAPK via up-regulation of toll like receptor 9 (TLR9). Associated with JNK activation, annexin V-PI staining indicated that HHV-6A was a strong inducer of apoptosis. Apoptotic response associated cytokines, IL-6 and TNF-alpha also induced by HHV-6A infection. PMID- 22055433 TI - Pain relief report commended for highlighting self-management, integrative approaches. PMID- 22055434 TI - Role of nitrite in flavour development in uncooked cured meat products: Sensory assessment. AB - Fermented dry sausages were produced according to the current industrial practices with the only exception that sodium nitrite was not systematically included in the formulation. Finished products were evaluated by a trained taste panel. Flavour of the samples made from mixes with added nitrite was found significantly different from that of the nitrite-free samples. Basically, nitrosated samples were allotted a stronger and a more typical flavour. PMID- 22055435 TI - Thawing of lamb loin chops in air and CO(2). Effect on colour and drip. AB - Colour retention and drip loss was assessed during retail display for chilled lamb chops displayed fresh or stored in CO(2) for 7 weeks before display, and for chops frozen for various times and thawed in air or CO(2). A sensory panel found fresh lamb chops to have an acceptable display life of 1 day, while chops which had been frozen for 1 day and then thawed lasted 2 days. Holding chops for 7 weeks in a CO(2) atmosphere at - 1.5 degrees C improved display life to 3 days, but frozen chops held for 7 weeks before thawing had deteriorated in colour, and only one group was acceptable on the initial day of display. Initially there were no differences in Hunter L values (brightness) due to treatment, but chilled chops or those frozen for 1 day showed a greater increase in L values by the second day than those frozen for 7 weeks, after which there was no change in brightness. Hunter a values (redness) were higher in chilled chops and those thawed after 1 day's frozen storage than those frozen for 7 weeks before thawing. Hunter b values (yellowness) were greater at all times in chilled chops held for 7 weeks and varied amongst the other treatments. The measured per cent drip from chops frozen for only 1 day was greater on thawing than drip from chops frozen for 7 weeks before thawing. Drip during display, assessed by a sensory panel, increased more in those chops stored either chilled or frozen for 7 weeks before display. PMID- 22055436 TI - The thickness and quality of backfat in various pig breeds and their relationship to intramuscular fat and the setting of joints from the carcasses. AB - The characteristics of backfat were measured in carcasses from 233 pigs representing eleven breeds. Animals were fed ad libitum and killed at an average live weight of 62 kg. In breeds in which the backfat was thicker it was also firmer and contained less water. In leaner breeds there was reduced cohesiveness of fat and muscle components of the loin joint so that the fat separated more easily from the underlying lean. This contributed to joints which were subjectively assessed as less firm and well set. Fatter breeds tended to have Longissimus muscles which contained more intramuscular fat. However, the relationship between muscle fat and carcass fat was poor suggesting that, if it was thought desirable to select for increased intramuscular fat in the interests of meat palatability, then this could be achieved without making carcasses undesirably fat. Differences in fat characteristics between breeds were apparently largely attributable to differences in fatness rather than inherent breed factors. PMID- 22055437 TI - The ultra-rapid chilling of lamb carcasses. AB - Experiments were carried out on the effects of chilling lamb carcasses very rapidly in a pre-rigor condition. The chilling regime which was finally used was to cool the carcasses at an ambient temperature of -20 degrees C and an air speed of 1.5 m/s for 3.5 h. Examination of striploins from carcasses subjected to this chilling regime showed that, after 7 day's storage, the meat was as tender as that from carcasses which had been conventionally chilled at 4 degrees C for 24 h There were significant reductions in weight loss as a result of ultra rapid chilling, compared to conventionally chilled carcasses. The reductions obtained after 24 h varied between 0.8 and 0.9%, depending on whether the carcasses were washed or unwashed. PMID- 22055438 TI - Studies on emulsion-type buffalo meat sausages incorporating skeletal and offal meat with different levels of pork fat. AB - Ready-to-eat emulsion-type buffalo meat sausages were developed by using a combination of 80% meat components with 20% pork back fat. The meat components were constituted of 70 parts buffalo skeletal meat and 30 parts offal meat (rumen meat and heart meat in equal proportions). The emulsion stability, cooking losses of emulsions and sausages, composition of cooked sausages, eating quality of sausages and the microscopic characteristics of the raw emulsion and cooked sausages were studied. The light microscope micrograph of the raw emulsion showed uniformly well distributed fat globules embedded in a dense protein gel. The cooked emulsion also showed uniformly sized fat globules well distributed in a fine, compact, coagulated protein gel, which retained their original spherical shape. Good quality emulsion-type sausages could be produced having a high emulsion stability (0.87 +/- 0.07 ml fat release/100 g emulsion); a low emulsion cooking loss (9.60 +/- 0.60%) and a low sausage cooking loss (8.83 +/- 0.48%). The overall acceptability of sausages was also high. PMID- 22055439 TI - Characterization of changes in psychometric colour attributes of comminuted porcine lean meat during processing. AB - Changes in colour during the processing of a comminuted porcine lean meat system were characterized using the psychometric colour attributes lightness L (*)) hue (h (*))and chroma (C (*)). The effects of processing temperature, nitrite and air pressure during comminution were examined. The pattern of changes as a function of processing time for L (*) and C (*), but not for h (*), showed clear dependence on processing temperature (15, 30, 40, 50 and 60 degrees C). For C (*) this dependence was much more complex than foor L (*). Nitrite dramatically affected the pattern of change in h (*) and C (*), but much less so changes in L (*). Varying the air pressure during comminution did not induce shifts in patterns of changes of the three colour attributes. However, it did have a marked effect on the absolute values and the extent of changes in L (*) and, to a much lesser extent, in h (*) and C (*). The findings of this study furnish the basis for a possible usage of the psychometric colour attributes as parameters for a quantitative kinetic analysis and modelling of the effect of processing factors during the production of comminuted meats. PMID- 22055440 TI - Modified packaging as protection against photodegradation of the colour of pasteurized, sliced ham. AB - Carbon dioxide flushing and packaging under slight overpressure has been found to eliminate discoloration of vacuum-packed ham, normally encountered as a result of photooxidation of nitric oxide pigments during the first 24 h of display in illuminated cabinets. On exposure to light, even when the product is packed in high-vacuum, residual oxygen invariably present in the product gives rise to significant photochemical pigment degradation and general poor oxidative stability, and has warranted up to 4 days of dark storage prior to display. Replacement of the atmosphere with carbon dioxide, even when repeated, followed by the establishment of vacuum, does not yield a similar protection. PMID- 22055442 TI - Post-mortem energy metabolism in bovine muscles studied by non-invasive phosphorus-31 nuclear magnetic resonance. AB - Phosphorus-31 Nuclear Magnetic Resonance ((31)P-NMR) has been utilized to follow non-invasively the post-mortem metabolism of the major phosphorylated metabolites in muscles from beef slaughter carcasses. In addition to adenosine-5' triphosphate (ATP), creatine phosphate (CP) and inorganic phosphate (P(i)) considerable amounts of glucose- and fructose-6-phosphate (G6P and F6P, respectively) as well as glycerol-3-phosphate (Glyc3P) were detected. ATP was mainly present as a Mg(2+)-ATP complex. Adenosine-5'-diphosphate (ADP) appeared to be mainly bound to muscle proteins. A good quantitative agreement was found for the levels of ATP, CP and sugar phosphates (SP) when estimated by NMR or enzymatic assays. Since the chemical shifts of the P(i) and sugar phosphate resonances are a function of the pH, the intracellular pH could be directly deduced from the NMR spectra. Values obtained in this manner were, within the errors of both methods, the same as those determined in iodoacetate/KCl homogenates. The pH gradients within the tissue never exceeded 0.3 pH units. In a final set of experiments we used (31)P-NMR 10 study the effects of electrical stimulation on the intracellular pH and post-mortem metabolism. It was concluded that (31)P-NMR, due to its non-invasive nature plus the fact that some of the NMR parameters are sensitive to the intracellular environment, provides a useful complement to existing methods for the study of post-mortem metabolism. PMID- 22055443 TI - Cold-shortening toughness in excised pork M. Longissimus dorsi. AB - Excised pork M. Longissimus dorsi from six Large White Cross pigs were subjected to a range of chilling rates using temperatures between 20 degrees C and -20 degrees C. Onset of rigor at 20 degrees C varied from 3 to 7.5 h between animals and rigor was complete in 6.5 to 15 h. Cold-shortening was induced when samples were chilled in air or liquid at 3 degrees C or below but not at 5 degrees C or ambient. The highest cooling rate, using liquid at -1 degrees C, reduced the meat samples to 10 degrees C in about 1 h and induced 34% shortening. After ageing for 5 days at 3 degrees C in 26 h. Considering all chilling rates, toughness increased as the time to reach 10 degrees C decreased to 3 h or less. Extensive cold-toughening would be unlikely to occur in current UK commerce and any toughening which did occur would be confined to Longissimus dorsi M. in about 20% of carcasses. The projected increased introduction of very rapid cooling, particularly in conjunction with lean pig production and hot deboning of pork, could toughen all cuts in about 60% of carcasses. PMID- 22055444 TI - Skeletal muscle characteristics in different breeds of pigs in relation to sensory properties of meat. AB - Fibre type composition, activities of enzymes used as indicators for oxidative (citrate synthase and 3-OH-acyl-coA dehydrogenase) and glycolytic (lactate dehydrogenase and triose phosphate dehydrogenase) capacity as well as glycogen and triglyceride levels were analysed on muscle biopsies (M. longissimus dorsi and M. gluteus medius) obtained preslaughter from pure breed Hampshire (n = 5), Swedish Landrace (n = 5) and Swedish Yorkshire (n = 5) pigs. The biopsied muscles were evaluated after slaughter for the sensory properties of the meat. Fibre type composition was similar in all breeds, whereas the metabolic profile differed. The Hampshire pigs had a significantly higher oxidative capacity, lower glycolytic capacity, and greater storage of both glycogen and triglycerides compared with the Yorkshire pigs. Values for the Swedish Landrace pigs were inbetween the other breeds. Tenderness of meat was significantly lower in the Yorkshire pigs compared with the other breeds. These results suggest that of the sensory properties of meat, tenderness seems to be especially related to the metabolic profile of the muscles in the living pig. PMID- 22055445 TI - Pork of low technological quality with a normal rate of muscle pH fall in the immediate post-mortem period: The case of the Hampshire breed. AB - The aim of the experiment was to determine the technological properties of meat from Hampshire pigs, as compared to good quality meat from Large White pigs and to exudative meat from halothane-positive (HP) Pietrain pigs. All Hampshire and Large White pigs were halothanenegative (HN). In 129 females and castrated males (47 Large White, 20 HN Pietrain, 27 HP Pietrain, 35 Hampshire), several quality characteristics were measured on raw meat and one ham was processed into cooked 'Paris ham'. Although the pH was normal I h post mortem in Hampshire pigs (which, in this respect, did not differ from Large White pigs) pork from Hampshire pigs, especially females, showed a very low ultimate pH and the highest cooking loss in processing. However, meat was much less exudative when fresh and generally darker (reflectance measured at 630 nm or subjective colour score) in Hampshire than in HP Pietrain pigs. A low ultimate pH occurred in muscle from Hampshire pigs owing to a very high 'glycolytic potential' (essentially glycogen content). It is proposed to use the term 'Hampshire type' to denote meat whose qualitative inadequacies basically result from an abnormally lowered ultimate pH, and to keep the term 'PSE' to refer to meat whose exudative state comes from an abnormally rapid pH fall in the immediate postmortem period. PMID- 22055446 TI - The impact of organochlorines cycling in the cryosphere on their global distribution and fate--1. Sea ice. AB - Global fate and transport of gamma-HCH and DDT was studied using a global multicompartment chemistry-transport model, MPI-MCTM, with and without a dynamic sea ice compartment. The MPI-MCTM is based on coupled ocean and atmosphere general circulation models. Sea ice hosts 7-9% of the burden of the surface ocean. Without cycling in sea ice the geographic distributions are shifted from land to sea. This shift of burdens exceeds the sea ice burden by a factor of ~8 for gamma-HCH and by a factor of ~15 for DDT. As regional scale seasonal sea ice melting may double surface ocean contamination, a neglect of cycling in sea ice (in an otherwise unchanged model climate) would underestimate ocean exposure in high latitudes. Furthermore, it would lead to overestimates of the residence times in ocean by 40% and 33% and of the total environmental residence times, tau(overall), of gamma-HCH and DDT by 1.6% and 0.6%, respectively. PMID- 22055447 TI - Comparison of chemical composition of meat determined at eight laboratories. AB - Sixteen minced samples of lean beef M. semimembranosus and M. gracilis were analysed for nitrogen, fat, moisture, collagen, ash and pH using recommended procedures in eight European Communitie' (EC) meat research laboratories. Differences between replicate determinations within laboratories were often larger than suggested in reference methods although they were smaller than the differences between laboratories. Moisture and pH were determined most consistently, collagen least consistently. PMID- 22055448 TI - The cooking of single myofibres, small myofibre bundles and muscle strips from beef M. psoas and M. sternomandibularis muscles at varying heating rates and temperatures. AB - When single myofibres are heated in an aqueous medium up to temperatures of 90 degrees C at pH 5.5, they do n ot shorten but instead decrease in diameter. This decrease begins slowly at 40 degrees and reaches a maximal rate and extent at 60 degrees , when the myofibre volume has decreased to 50% of the initial volume and about 60% of the cell water has been expelled. The myofibres behave similarly when the pH of the medium is raised to 6.8, but the loss of cell water is considerably less (about 42%). When small myofibre bundles are heated from 10 degrees to 60 degrees they behave similarly to single myofibres by decreasing, in diameter only, from 40 degrees to about 63 degrees . At the latter temperature their volume has decreased to 60% of the initial value and about 48% of the bundle water has been expelled. Above 64 degrees the bundles shorten, the shortening reaching about 30% of the initial length at 90 degrees . This shortening, combined with the diameter decrease, leads to a volume decrease to 43% of the initial value and to a loss of about 68% of the cell water. PMID- 22055449 TI - Effects of low voltage electrical stimulation on mature cow carcasses: Part 1 Selected quality attributes of beef. AB - The quality characteristics of semitendinosus (ST) and longissimus dorsi (LD) roasts obtained from mature carcasses subjected to extra low voltage (50-100 V) electrical stimulation (ES) were determined. ES was applied for 2 min with voltage increases to either 50 V (ES1) or 100 V (ESII). Evaluationss were conducted on meat obtained from control sides (no ES) aged for either 48h or 7 days and from ES carcasses aged for 48h. ES caused a reduction (P < 0.1) in pH values 1 and 4h post mortem. At 24h, the pH of each of the muscles from ES and control carcasses was similar. There were no differences in raw rib-eye muscle colour, firmness or texture due to ES. Cooking losses of ST and LD did not appear to be affected by either ES or increased ageing of control roasts. For both ST and LD roasts, trained panellists generally detected no significant effects of ES or ageing time (for no ES roasts) on palatability. Consumer panel judgements of ST roasts were similar to those of the trained judges. Water-holding capacity, tenderness (OTMS) and softness (penetrometer) data for ST and LD roasts generally support findings from sensory evaluation. Cooking and eating quality characteristics of ST and LD roasts from mature cow carcasses subjected to ES were similar to those of the controls. PMID- 22055450 TI - Structural and palatability relationships in frozen ground beef patties as a function of freezing treatments and product formulation. AB - Four freezing rates for ground beef patties were evaluated for product quality effects and microstructural changes. These rates were further evaluated for different pattie formulations involving post-rigor and pre-rigor meat. Both light microscopy (LM) and scanning electron microscopy (SEM) were utilised for microstructural comparisons. Fast freezing rates had a positive effect on pattie quality, resulting in increased juiciness, tenderness and overall acceptability. Photomicrographs showed increased ice cavity size with decreased freezing rates, which probably contributed to increased cooking shrink and tenderness changes observed. Pre-rigor patties compared very favourably with conventional post-rigor beef patties and showed no obvious structural differences. PMID- 22055451 TI - An assessment of extracellular space measurements in post-mortem muscle. AB - Extracellular space measurements of early post-mortem muscle were made by incubating muscle strips in inulin [(14)C] carboxylic acid. The extracellular space measurements provide a means to assess the functionality of the muscle membrane. This may lead to an understanding of variations in the water-holding capacity of meat and the effects of stress on the muscle membranes of stress susceptible animals. Secondly, a level of intrafibre water affinity between carcasses may be determined which may relate to the interfilamental spacings between myofibrils in the fibre and thus meat quality. PMID- 22055452 TI - Factors affecting paddy soil arsenic concentration in Bangladesh: prediction and uncertainty of geostatistical risk mapping. AB - Knowledge of the spatial correlation of soil arsenic (As) concentrations with environmental variables is needed to assess the nature and extent of the risk of As contamination from irrigation water in Bangladesh. We analyzed 263 paired groundwater and paddy soil samples covering highland (HL) and medium highland-1 (MHL-1) land types for geostatistical mapping of soil As and delineation of As contaminated areas in Tala Upazilla, Satkhira district. We also collected 74 non rice soil samples to assess the baseline concentration of soil As for this area. The mean soil As concentrations (mg/kg) for different land types under rice and non-rice crops were: rice-MHL-1 (21.2)>rice-HL (14.1)>non-rice-MHL-1 (11.9)>non rice-HL (7.2). Multiple regression analyses showed that irrigation water As, Fe, land elevation and years of tubewell operation are the important factors affecting the concentrations of As in HL paddy soils. Only years of tubewell operation affected As concentration in the MHL-1 paddy soils. Quantitatively similar increases in soil As above the estimated baseline-As concentration were observed for rice soils on HL and MHL-1 after 6-8 years of groundwater irrigation, implying strong retention of As added in irrigation water in both land types. Application of single geostatistical methods with secondary variables such as regression kriging (RK) and ordinary co-kriging (OCK) gave little improvement in prediction of soil As over ordinary kriging (OK). Comparing single prediction methods, kriging within strata (KWS), the combination of RK for HL and OCK for MHL-1, gave more accurate soil As predictions and showed the lowest misclassification of declaring a location "contaminated" with respect to 14.8 mg As/kg, the highest value obtained for the baseline soil As concentration. Prediction of soil As buildup over time indicated that 75% or the soils cropped to rice would contain at least 30 mg/L As by the year 2020. PMID- 22055453 TI - Short-term effects of particulate matter on total mortality during Saharan dust outbreaks: a case-crossover analysis in Madrid (Spain). AB - BACKGROUND: The role of Saharan dust outbreaks on the relationship between particulate matter and daily mortality has recently been addressed in studies conducted in Southern Europe, although they have not given consistent results. METHODS: We investigated the effects of coarse (PM(10-2.5)) and fine particulate matter (PM(2.5)) in Madrid on total mortality during Saharan dust and non-dust days using a case-crossover design. RESULTS: During Saharan dust days, an increase of 10mg/m(3) of PM(10-2.5) raised total mortality by 2.8% compared with 0.6% during non-dust days (P-value for interaction=0.0165). CONCLUSION: We found evidence of stronger adverse health effects of PM(10-2.5) during Saharan dust outbreaks effects for impacted European populations, but not for PM(2.5). Further research is needed to understand mechanisms by which Saharan dust increases risk of mortality. PMID- 22055454 TI - Repeated administration of exendin-4 reduces focal cerebral ischemia-induced infarction in rats. AB - Exendin-4 is a GLP-1 agonist that is clinically used for the treatment of diabetes mellitus and may also have neuroprotective effect. We explored the effect of repeated administration of exendin-4 (0.5 MUg/kg, intraperitoneal twice a day for 7 days) on infarct volume, neurological deficit (neurological score, grip test, foot fault and rota rod tests), oxidative stress parameters (malondialdehyde, reduced glutathione, and superoxide dismutase) and expression of endothelin (ET) ET(A) and ET(B) receptors following cerebral ischemia produced in rats by permanent middle cerebral artery occlusion (MCAO). Since ET(A) receptors in the central nervous system (CNS) are involved in cerebral ischemia, we determined the effect of a specific ET(A) receptor antagonist, BQ123 (1mg/kg, intravenously administered thrice: 30 min, 2h and 4h after MCAO for a total dose of 3 mg/kg) on cerebral ischemia in control and exendin-4 treated rats. Results indicate that exendin-4 treated rats had significant protection following MCAO induced cerebral ischemia. The infarct volume was 27% less compared to vehicle treated rats. The neurological deficit following MCAO was lower and oxidative stress parameters were improved in exendin-4 treated rats compared to control. BQ123 significantly improved infarct volume, oxidative stress parameters and neurological deficit in ischemic rats treated with vehicle or exendin-4. BQ123 induced protection from cerebral ischemia was similar in vehicle or exendin-4 treated rats. Expression of ET(A) receptors was significantly increased following cerebral ischemia which was not affected by exendin-4 treatment or by BQ123 administration. No change in expression of ET(B) receptors was observed following cerebral ischemia or any treatment. It is concluded that exendin-4 protects the CNS from damage due to cerebral ischemia by reducing oxidative stress and is independent of ET receptor involvement. PMID- 22055455 TI - Selective loss of AMPA receptor subunits at inhibitory neuron synapses in the cerebellum of the ataxic stargazer mouse. AB - AMPA receptor subunits (GluA1-4) are trafficked to membrane synaptic sites by transmembrane AMPA receptor regulatory proteins (TARPs). In the stargazer mutant mouse, expression of TARP-gamma2 (stargazin) is severely reduced, resulting in cerebellar ataxia. Stargazer granule cells (GCs) have a complete loss of functional AMPARs, as gamma2 is their main TARP; hence mossy fiber (MF)-GC synapses are silent. The aim of the current study was to investigate how the stargazin deficit affects expression levels of AMPAR subunits at output synapses from GC parallel fibers (PF) onto inhibitory neurons in the molecular layer. Cerebella from male litter-pairs of stargazer and control mice were analyzed by post-embedding immunogold-microscopy. Levels of GluA2/3 and GluA4 were evaluated by measuring relative density of immunogold at PF-Purkinje cell (PF-PC) and PF interneuron (PF-In) synapses respectively. In total, 100 synapses were analyzed in each pair of stargazer and control littermates. GluA2/3 and GluA4 expression was significantly reduced throughout the stargazer cerebellar cortex. GluA2/3 levels were reduced by 52% (p<0.001) at PF-PC synapses, and GluA4 levels by 31% (p<0.001) at PF-In synapses in stargazers. In neither case, however, was there a total loss of synaptic AMPAR subunits as occurs at MF-GC synapses. As the inhibitory neurons of the molecular layer express other TARPs in addition to stargazin, TARP compensation may limit the loss of GluA subunits at these synapses and explain why they are not silent like the MF-GC synapses. These data suggest that the ataxic phenotype in stargazers is primarily due to absence of AMPARs at cerebellar MF-GC synapses. PMID- 22055456 TI - Effects of significance of auditory location changes on event related brain potentials and pitch discrimination performance. AB - We examined effects of significance of task irrelevant changes in the location of tones on the mismatch negativity (MMN) and P3a event related brain potentials. The participants were to discriminate between two frequency modulated tones differing from each other in the direction of frequency glide. Each tone was delivered through one of five loudspeakers in front of the participant. On most trials, a tone was presented from the same location as the preceding tone, but occasionally the location changed. In the Varying Location Condition, these changes, although irrelevant with regard to pitch discrimination, were still significant for performance as the following tones were presented from the new location where attention had to be therefore shifted. In the Fixed Location Condition, the location changes were less significant as the tones following a location change were presented from the original location. In both conditions, the location changes were associated with decreased hit rates and increased reaction times in the pitch discrimination task. However, the hit rate decrease was larger in the Fixed Location Condition suggesting that in this condition the location changes were just distractors. MMN and P3a responses were elicited by location changes in both conditions. In the Fixed Location Condition, a P3a was also elicited by the first tone following a location change at the original location while the MMN was not. Thus, the P3a appeared to be related to shifting of attention in space and was not tightly coupled with MMN elicitation. PMID- 22055457 TI - Vancomycin-resistant enterococci rectal colonization in an intensive care unit: a report from Turkey. PMID- 22055458 TI - Nosocomial infections in a pediatric residential care facility. AB - BACKGROUND: Nosocomial infections have rarely been characterized in pediatric residential care facilities. The purpose of this study is to assess the frequency of and risk factors for infectious diseases in pediatric residential care facilities over a 1-year period and to contrast them with other pediatric extended care facilities. METHODS: A retrospective chart review was performed at a pediatric residential care facility dedicated exclusively to children with severe physical and mental disabilities. Incidence rates of infection were collected on a census of 109 residents from January 1 through December 31, 2009. Infectious diseases were classified using ICD-9-CM codes. PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched to identify similar studies. RESULTS: In 2009, the overall incidence rate of infection was 6.21 per 1,000 resident-days of care, with the most frequent being streptococcal or staphylococcal skin infections (1.11 per 1,000 resident-days) and the least frequent being conjunctivitis (0.16 per 1,000 resident-days). Extensive literature reviews yielded 2 published studies that evaluated infections in pediatric extended care facilities; these studies exhibited distinct prevalences of infectious diseases when compared with the current study. CONCLUSION: Studies examining nosocomial infections should not consider pediatric extended care facilities as 1 single entity given the heterogeneity among these facilities. PMID- 22055459 TI - Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. AB - Mesenchymal stem cells (MSCs) can promote tumor growth in a mouse xenograft model, but the exact mechanism remains unclear. In this study, we investigated the effects of bone marrow MSC-derived exosomes (MSC-exosomes) on tumor growth in vitro and in vivo. Our results showed that MSC-exosomes promoted tumor growth in vivo. MSC-exosomes enhanced vascular endothelial growth factor (VEGF) expression in tumor cells by activating extracellular signal-regulated kinase1/2 (ERK1/2) pathway. Inhibition of ERK1/2 activation reserved the increase of VEGF level by MSC-exosomes. Our findings demonstrate a new mechanism through which MSC-exosome mediated cell-cell interactions may contribute to tumor progression. PMID- 22055460 TI - TSC1/TSC2 inactivation inhibits AKT through mTORC1-dependent up-regulation of STAT3-PTEN cascade. AB - Aberrant activation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss or inactivation of TSC1/TSC2 protein complex, leads to negative feedback inhibition of Akt. The exact mechanisms of this process are still not fully understood. Here we present evidence for the involvement of STAT3, a known mTORC1 regulated transcription factor, in this process. We demonstrate that STAT3 promotes the transcription of PTEN by directly binding on the PTEN promoter. Elevated PTEN then inhibits the proliferation of Tsc1(-/-) or Tsc2(-/-) cells through down-regulation of Akt signaling. Activation of PTEN in this pathway may thus serve as a protective mechanism against hyper-activated mTORC1 mediated tumorigenesis and contribute to the benign nature of tumors caused by loss of either TSC1 or TSC2. PMID- 22055461 TI - Histone H2A.Z prepares the prostate specific antigen (PSA) gene for androgen receptor-mediated transcription and is upregulated in a model of prostate cancer progression. AB - The histone variant H2A.Z is present at many eukaryotic gene regulatory regions and can affect rates of transcription. Here we show that total H2A.Z and an acetylated form of H2A.Z is mainly present at the prostate specific antigen (PSA) enhancer and promoter in prostate cancer cell lines where the gene is expressed, but the levels decrease during rapid cycles of transcription. Treatment of prostate cancer cells with androgen results in increased H2A.Z levels due to upregulation of the H2A.Z-1, but not the H2A.Z-2 gene. This upregulation is likely the result of increased MYC transcription factor binding that occurs in response to androgen at the H2A.Z-1 promoter. Furthermore, we show that in a LNCaP xenograft model of prostate cancer progression, there is a significant increase of H2A.Z protein in castration resistant LNCaP tumors resulting from increased expression of the H2A.Z-1 gene. While a similar trend was observed in samples from prostate cancer patients, the results were not statistically significant. Nevertheless, there may be a subset of prostate cancers where elevated expression of H2A.Z-1 is indicative of prostate cancer progression to androgen independence. PMID- 22055462 TI - Meat emulsion functionality related to fat-protein ratio and selected dairy and cereal products. AB - The influence of fat-protein ratio, moisture content, buttermilk powder, modified wheat flour, corn starch and modified waxy maize flour in processed meat emulsions upon their sensory attributes, textural profile parameters, and selected functional properties were investigated. These properties were optimized using regression models, canonical analysis, response surface methodology, and a multidimensional optimization algorithm. PMID- 22055463 TI - Activities of metabolic and contractile enzymes in 18 bovine muscles. AB - Contractile and metabolic characteristics of 18 bovine muscles were studied using 10 animals of various ages (2-10 years), sexes (females, males and castrated males) and types (dairy, meat or crossbred). Contractile type was assessed by measuring myofibrillar Ca?-Mg-activated ATPase activity. Metabolic type was appraised by determining phosphorylase, glycogen synthetase, hexokinase, haem iron as well as glycolytic and mitochondrial oxidative activities. 'Glycolytic potential' and buffer capacity (as change in lactate concentration as a function of change in pH) were measured. The results showed that myofibrillar ATPase activity was positively related to glycolytic activities and negatively related to oxidative activities. Ultimate pH was negatively correlated with myofibrillar ATPase activity and had little if any relationship to the glycolytic potential. Metabolic and contractile activities were essentially unaffected by sex, age or breed type. PMID- 22055464 TI - Packaging conditions for extended storage of chilled dark, firm, dry beef. AB - Normal-pH (5.5-5.7) and high-pH (> 6.0) beef cuts of 500g were vacuum packaged in polyvinylidene chloride (PVDC), metalized polyester or aluminium foil laminates, or in foil laminate packs inflated with 1 litre of CO(2). During storage at + 1 degrees C. vacuum packaged cuts developed spoilage floras of lactobacilli and enterobacteria; cuts stored under CO(2) developed floras of lactobacilli alone. Floras on all high-pH vacuum packaged cuts approached maximum numbers after 6 weeks' storage. At this time, cuts in PVDC laminate showed early symptoms of spoilage, but such symptoms did not develop in other vacuum packaged high-pH cuts until 9 or more weeks. Similarly, normal-pH cuts in PVDC film showed spoilage symptoms at 12 weeks, but such symptoms did not develop in other vacuum packaged normal-pH cuts until 15 weeks. Both normal- and high-pH cuts packaged under CO(2) were unspoiled at 15 weeks. PMID- 22055465 TI - Salt-induced swelling of meat: The effect of storage time, pH, ion-type and concentration. AB - The effect of hypertonic salt solutions on meat fibres has been studied as a function of post-mortem storage. Rabbit longissimus dorsi fibres (after about 20 h post-mortem storage at 4 degrees C), were found to swell in hypertonic salt solutions, such as 0.25m KI or 0.6m KCl, to two to three times their original diameter. This swelling occurred in the fibre transverse plane only. X-ray diffraction shows swelling occurs by a combination of an increase in the myofilament lattice spacing and a loss of myofilament order. Fibre swelling is highly co-operative. At pHs below the isoelectric point of the myofibrillar proteins, hypertonic salt solutions induce fibre shrinkage. The post-mortem time course of response shows a peak at 18-35 h bounded by periods of minimal or zero response. We propose that the collagenous endomysial sheath acts as a restraint to myofibril swelling and that the characteristics of post-mortem swelling are a balance of the myofibrillar propensity to swell and the constraint of the endomysium. PMID- 22055466 TI - More than just lysins: peptidoglycan hydrolases tailor the cell wall. AB - Enzymes that degrade the peptidoglycan (PG) cell wall layer called PG hydrolases or autolysins are often thought of as destructive forces. Phages employ them to lyse their host for the release of virion particles and some bacteria secrete them to eliminate (lyse) their competition. However, bacteria also harness the activity of PG hydrolases for important aspects of growth, division, and development. Of course, using PG hydrolases in this capacity requires that they be tightly regulated. While this has been appreciated for some time, we are only just beginning to understand the mechanisms governing the activities of these 'tailoring' enzymes. This review will focus on recent advances in this area with an emphasis on the regulation of PG hydrolases involved in cell division. PMID- 22055467 TI - Characterization of the settling process for wastewater from a combined sewer system. AB - Among the methods used for determining the parameters necessary for design of wastewater settling tanks, settling column tests are used most commonly, because of their simplicity and low costs. These tests partly mimic the actual settling processes and allow the evaluation of total suspended solids (TSS) removal by settling. Wastewater samples collected from the Liguori Channel (LC) catchment in Cosenza (Italy) were subject to settling column tests, which yielded iso-removal curves for both dry and wet-weather flow conditions. Such curves were approximated well by the newly proposed power law function containing two empirical parameters, a and b, the first of which is the particle settling velocity and the second one is a flocculation factor accounting for deviations from discrete particle settling. This power law function was tested for both the LC catchment and literature data and yielded a very good fit, with correlation coefficient values (R(2)) ranging from 0.93 to 0.99. Finally, variations in the settling tank TSS removal efficiencies with parameters a and b were also analyzed and provided insight for settling tank design. PMID- 22055468 TI - Scanning electron micrographs of Oryzophagus oryzae (Coleoptera, Curculionidae), plastron structure and swimming behavior. AB - The morphological structures that permit Oryzophagus oryzae aquatic activities and swimming behavior were studied and compared with various weevils and other relevant species. The use of scanning electron microscopy facilitated the recognition of three different hydrofuge scales and sensilla. Based on the microscopic observations of behavior, morphological evidence, and comparisons with other curculionid species, it was supported that the gas exchange in O. oryzae adults relies on a subelytral air store maintained by hydrofuge scales and a ribbed margin on the adult elytra. The plastron structure is identical to Lissorhoptrus oryzophilus supporting the application of similar control measures for both species. PMID- 22055470 TI - Examination of cathepsins B, D, H and L activities in dry-cured hams. AB - Cathepsins B, D, H and L as well as the glycosidases beta-glucuronidase and N acetyl-beta-glucosaminidase were assayed for activity in fresh pork muscles stored for up to 20 days at 4 degrees C and in 3- and 8-month dry-cured hams. Cathepsin B, H and L activities fell by 40-79% after 20 days while cathepsin D activity remained unchanged. All the enzymes were still active after 8 months of dry curing; with the recoveries found to be in the range 14-73%. Contaminant microorganisms did not appear to contribute to the observed proteinase activities. Cathepsins B, H and L activities from the 8-month ham have been confirmed as cysteine proteinases by the use of specific inhibitors. It was further confirmed that the cathepsin B and L activities in fresh pork and dry cured ham were similar by isoelectrofocusing. We suggest that the presence of the curing salts may be important in stabilising the muscle enzymes during the curing process. PMID- 22055471 TI - Fibre optic probe measurements in landrace pigs of different halothane phenotypes. AB - Fibre Optic Probe (FOP) measurements were made in the longissimus dorsi muscle of 70 halothane-positive (HP) and 70 halothane negative (HN) pigs of a synthetic Landrace strain at 45 min (FOP(1)), 3 h (FOP(3)) and 17h (FOP(17)) post mortem. Measurements of pH, rigor and temperature were also made in the slaughterline. Carcasses were sampled (longissimus dorsi, 2-4 lumbar vertebrae) at 18h post mortem and meat quality objectively assessed. The incidence of slight PSE (visual score) was 49% in HP and 10% in HN pigs, while the incidence of serious PSE was 20% and 4%, respectively. Yet, the percentage drip loss during 48 h storage in HN/PSE pigs was higher than in HP/PSE pigs (10.2 vs 7.5%), which was associated with a lower ultimate pH (5.25 vs 5.44). Therefore, it is suggested that the remaining PSE problem in HN Landrace pigs, although less in frequency, might be more serious. In the whole population, of all FOP measurements taken correlations with colour (Hunter L(*)-value) and percentage drip loss were highest for the FOP(17) measurements (r = 0.82 and 0.69, respectively). FOP(1) was better related than pH(1) to colour, while the relationships with drip loss were of a similar magnitude. Differences in FOP values between HP and HN pigs were larger for FOP(1) (148 vs 108) than for FOP(3) (148 vs 125) or FOP(17) (153 vs 130). The relationship between FOP1 and ultimate meat colour (L(*)-value) appeared to be higher in HP (0.60) than in HN (0.48) pigs, while for the relationship between FOP(1) and percentage drip loss the reverse was true (0.48 and 0.60, respectively). The effect of halothane phenotype on the relationships found, may partially explain the different results of reflectance measurements reported in the literature as to their predictive value for ultimate meat quality. The results suggest that the measurement of reflectance in the slaughterline offers opportunities for identifying (potential) PSE carcasses. The large genetic influence of halothane phenotype on this parameter, may eventually justify its use as a base for payment for meat quality to the producer. PMID- 22055472 TI - Extending the retail storage time of pork sausage using modified atmospheres and freezing. AB - Two experiments were conducted to evaluate the effect of different gas mixtures on the keeping quality of fresh pork sausages. The modified atmospheres consisted of combinations of oxygen, carbon dioxide, and nitrogen. In the first experiment, 15 gas combinations of these two gases plus oxygen were evaluated. The samples were stored at 5 degrees C for up to 16 days. The variables used to evaluate the quality of the sausages included acceptability, hardness, cohesiveness, hue, pH, total plate counts, coliforms and water holding capacity. The results showed a negative effect of oxygen upon most of the variables. Based on these results, the second experiment was designed to evaluate the effect of frozen storage upon the quality of the samples against non-frozen storage (5 degrees C). Six gas combinations of carbon dioxide and nitrogen were used. The results favoured frozen storage and high carbon dioxide levels (60% to 80%). PMID- 22055473 TI - Influence of fishmeal, rape-seed, and rape-seed meal in feed on the fatty acid composition and storage stability of porcine body fat. AB - One hundred and ten pigs were fed test diets containing 1.1%, 3.3% or 5.5% fishmeal, 10% rape-seed or 15% rape-seed meal. The control diet contained soya bean meal. From each carcass M. longissimus dorsi, including subcutaneous fat, was taken and analysed for fatty acid composition and intramuscular fat content. Accelerated oxidation test was carried out on fresh samples. Sensory analyses as well as peroxide and aldehyde analyses were carried out after 0, 4, 6 and 9 months of freezer storage. The sensory properties of fresh meat and fat were not affected by any of the feed components tested. After 6 months of freezer storage slightly increased levels of off-flavours were noted with 3% fishmeal or more in the diet. Also, the peroxide value after storage increased at the same fishmeal level. With rape-seed or rape-seed meal in the diet the scores for off-flavours increased only slightly. A much lower storage stability was noted in fat from pigs fed a combination of rape-seed and fishmeal. Extra vitamin E in diets did not increase the storage stability of pork fat. Special attention was paid to the incorporation of dietary polyunsaturated fatty acids (PUFA), especially marine PUFA, into body fat. It was found that the incorporation of C22:6 was a very good indicator of the amount of fishmeal in the diet. PMID- 22055474 TI - Fatty acid composition of subcutaneous fat of sheep grazed on eight different pastures. AB - The levels of eight long chain fatty acids (14:0, 16:0, 16:1 17:0, 17:1, 18:0, 18:1, 18:2) were measured in the subcutaneous fat of S.A. Mutton Merino wethers (5 months old, 20-25 kg live mass, 8 per treatment) and, including 18:3, in eight pastures grazed for 84 days (maize stubble, Z. mays; Triticale; L. multiflorum; L. perenne; D. glomerata; D. eriantha; C. dactylon; M. sativa). Respectively, percentage fatty acid contents of subcutaneous fat and pastures were 14:0 5.04 +/ 0.86 and 0.67 +/- 0.37, 16:0 22.85 +/- 0.81 and 17.83 +/- 3.00, 16:1 2.07 +/- 0.22 and 2.42 +/- 1.17, 17:0, 1.68 +/- 0.04 and 0.42 +/- 0.16, 17:1 0.75 +/- 0.06 and 0.17 +/- 0.19, 18:0 25.94 +/- 2.02 and 4.95 +/- 1.68, 18:1 32.27 +/- 0.93 and 8.12 +/- 11.70, 18:2 1.59 +/- 0.36 and 15.89 +/- 5.16, 18:3 measured in pastures only 34.51 +/- 15.91. The palmitoleic acid (16:1) content of pastures increased (P < 0.05) as the ether extractable lipid content of the pastures increased. Pasture treatments influenced the levels of 14:0, 17:1 and 18:2 highly significantly (P < 0.01) and of 18:0 significantly (P < 0.05). Increasing levels of fatness of ribcut samples were associated with a decrease in 14:0 and an increase in 17:1 (P < 0.01) and an increase in 18:2 (P < 0.05). PMID- 22055475 TI - Effect of castration and cryptorchidism on fatty acid content of ovine adipose tissue. AB - Fatty acid analyses of perinephric and subcutaneous adipose tissue were made on 50 of Mehraban and Bakhriari breeds lambs to determine the effect of castration and cryptorchidism on ovine lipid composition. The level of stearic acid was significantly higher (p < 0.05) in cryptorchids than in wethers. Rams were also higher (p < 0.05) in the percentage of linoleic acid of the internal adipose tissue than wethers. The percentage of palmitic acid of subcutaneous tissue was higher (p < 0.05) in cryptorchid than rams. There was a tendency toward less saturated (palmitic and stearic) acids, but more unsaturated (oleic and linoleic) acids in rams than in wethers. The perinephric fat was more saturated than subcutaneous fat. PMID- 22055476 TI - Influence of animal diet and muscle location on cholesterol content of beef and pork muscles. AB - Muscles at three different anatomical locations from carcasses of 12 pigs and 12 steers that were fed diets with varying levels of oleic acid-pigs in the form of canola oil at levels of 0, 10 and 20% and steers in the form of canola rapeseed at levels of 0 and 20%-were analyzed for cholesterol concentrations. The cholesterol level of beef or pork muscles was not significantly affected by the animal diet modification. For each animal species, muscles at different anatomical locations were similar in cholesterol content. Beef and pork muscles were not significantly different in cholesterol content. PMID- 22055477 TI - Augmentation of cellular immunity and protection against influenza virus infection by bovine late colostrum in mice. AB - OBJECTIVE: We investigated whether oral administration of skimmed and concentrated bovine late colostrum (SCBLC) activates the immune system and protects against influenza virus (Flu) infection. METHODS: Murine Peyer's patch (PP) cells (2.5 105) were cultured in 0.1 ml RPMI-1640 supplemented with SCBLC at a concentration of 0, 0.1 or 1.0 mg/ml. To determine the levels of IL-12 and IFN , supernatants were collected on day 3. Mice were orally administered sterile saline solution (control group), or 400 g/g body weight (SCBLC 400 group) or 2,000 g/g body weight (SCBLC 2,000 group) of SCBLC for three weeks. These mice were measured for natural killer (NK) cells activity on PP cells, splenocytes and lung cells. Also, these mice in the control and SCBLC 2,000 groups were infected with Flu and were measured for the accumulated symptom rate. RESULTS: In PP cells cultured with SCBLC, the levels of IL-12 and IFN- were significantly increased in vitro. Oral administration of SCBLC to mice significantly increased NK cell activity of PP cells, splenocytes and lung cells. The accumulated symptom rate of the SCBLC 2,000 group was significantly lower than that of the control group in a mouse model of Flu infection. CONCLUSION: These results indicate that oral administration of SCBLC activates not only systemic cellular immunity but also local cellular immunity, such as in the respiratory tract, and that activation of cellular immunity is one of the mechanisms of amelioration of Flu infection. PMID- 22055478 TI - Enteral nutrition supplemented with L-glutamine in patients with systemic inflammatory response syndrome due to pulmonary infection. AB - OBJECTIVE: To evaluate the effect of enteral nutrition (EN) supplemented with l glutamine on glycolytic parameters, inflammation, immune function, and oxidative stress in moderately ill intensive care patients with sepsis. METHODS: Thirty patients received EN. Fifteen patients received EN supplemented with glutamine (30 g; GLN group) for 2 d followed by EN supplemented with calcium caseinate (30 g, CAS group), also over 2 d. The other 15 patients received EN with calcium caseinate (30 g; CAS group) for 2 d followed by EN with glutamine (30 g; GLN group), also over 2 days. One washout day with only EN was provided between every 2-d period of EN plus supplementation to all patients. Blood samples were taken before and after supplementation. RESULTS: There were no changes in glycolytic parameters in either group. Leukocytes decreased in the two groups (from 13 650 to 11 500 in the CAS group, P = 0.019; from 12.850 to 11.000 in the GLN group, P = 0.046). Lymphocytes increased in the GLN group (from 954 to 1916, P < 0.0001) and were more numerous after glutamine supplementation (from 1916 to 1085, P < 0.0001, GLN versus CAS). No significant changes were observed in interleukin levels, but urea levels were higher in the GLN compared with the CAS group (50.0 47.0, P = 0.030). Glutathione plasma concentrations did not differ significantly between the groups. No significant changes were observed in the plasma glutamine and glutamate concentrations. CONCLUSIONS: The EN supplemented with glutamine increased the lymphocyte count and helped to decrease lipid peroxidation but presented no effect on the antioxidant glutathione capacity and on cytokine concentrations or glycolytic parameters. PMID- 22055479 TI - Usefulness of the Malnutrition Screening Tool in patients with pulmonary tuberculosis. AB - OBJECTIVE: To examine the relation between the Malnutrition Screening Tool (MST) and the mortality of patients with pulmonary tuberculosis (TB). METHODS: Fifty two patients with pulmonary TB were analyzed. Nutritional assessment was carried out using the MST. The MST incorporates three components: presence of weight loss (score 0 or 2), amount of weight lost (score 1-4), and poor food intake or poor appetite (score 0 or 1). A score >=2 means that the patient is at risk for malnutrition. The Cox proportional hazard model was applied to assess the ability of the MST to predict prognosis. Receiver operating characteristic curve analysis was used to assess the MST score as a prognostic indicator in patients with pulmonary TB. To obtain optimal cutoff values for the MST score for the prognostic assessment in patients with TB, the maximum Youden index was used. RESULTS: For predicting the risk of mortality, the optimal cutoff value for the MST score was 2.5. Univariate and multivariate analyses identified age and a MST score >=3 as significant independent prognostic factors for survival. The patients with a MST score <3 had a median survival of 453 d and those with a MST score >=3 had a median survival of 242 d; the difference was statistically significant (P = 0.001). CONCLUSION: The MST appears to be a reliable tool for the nutritional risk assessment of patients with pulmonary TB. This risk assessment tool can play a valuable role in quickly identifying patients at an increased risk of death and providing adequate nutritional support. PMID- 22055480 TI - Daily vitamin supplementation and hypovitaminosis after obesity surgery. AB - OBJECTIVE: The objective of this study was to determine whether constant daily vitamin supplementation would be sufficient to prevent possible vitamin deficiencies in obese patients undergoing bariatric surgery. METHODS: The study was conducted on 58 men and women (mean age 41 +/- 10 y) who underwent Roux-en-Y gastric bypass RYGB and were assessed preoperatively and at 3, 6, and 12 mo after surgery. During the postoperative period, the patients received a multivitamin mineral supplement on a daily basis. RESULTS: Serum beta-carotene and vitamin C were lower starting from the third postoperative month and continued to be low after 12 mo, and vitamin A was decreased by the sixth month and increased by 12 mo. Vitamin B12 levels were stable up to 6 mo but were decreased by 12 mo. Folic acid levels increased from the third month and remained higher throughout follow up. One year after surgery there were 19% and 21% increases in the number of patients with vitamin A and vitamin C deficiency, respectively, and a 4% decreased of patients with folic acid deficiency. CONCLUSION: Weight loss and improvement in patients' general condition followed surgery, but serum levels of some vitamins were decreased despite the use of a vitamin-mineral supplement. These patients need continuous follow-up and individualized prescription of supplementation after the surgical procedure to prevent and treat vitamin deficiencies. PMID- 22055481 TI - High transfection efficiency of porcine peripheral blood T cells via nucleofection. AB - Transgenic technology is an effective approach to assess the roles of specific genes in the activation and differentiation of T cells and modify T cell qualities. However, porcine T cell transfection is poorly documented. Here, we developed a non-virus-based method for the transfection of resting and ConA stimulated porcine peripheral blood T cells using "Nucleofection" gene transfer technology; both plasmid DNA- and mRNA-mediated nucleofection systems were developed. The results demonstrated for the first time that plasmid DNA encoding green fluorescent protein (GFP) and in vitro transcribed GFP mRNA could be delivered efficiently into resting and activated porcine T cells. For both methods, the onset of gene expression was rapid and occurred within 2h post nucleofection. Optimised plasmid DNA-mediated nucleofection induced approximately 40% transgene expression with 51% cell viability in resting T cells and approximately 20% transgene expression with 53% cell viability in activated T cells at 24h post-gene delivery. However, optimised mRNA-based nucleofection resulted in higher transfection efficiencies and cell viability, with more than 50% transgene expression and 62% viability for resting T cells and approximately 40% transgene expression and 59% viability for activated T cells. Finally, we measured the impact of the developed nucleofection systems on T cell function by detecting the mRNA levels of the activation markers CD25, CD69 and the cytokine IFN-gamma; cell proliferation of the nucleofected resting peripheral blood mononuclear cells (PBMC) after ConA stimulation was also examined. The nucleofected resting PBMCs proliferated normally and up-regulated CD25, CD69 and IFN-gamma mRNA expression levels in a manner comparable to non-nucleofected cells. These results indicate that the developed nucleofection systems have no adverse effects on T cell function and can be utilised in swine immunological research. PMID- 22055482 TI - Freezing rate effects on the drip loss of frozen beef. AB - One of the quality parameters of frozen meat is the amount of exudate which arises during thawing. The amount of drip obtained by centrifugation under standard conditions, and the protein composition of the exudate, has been correlated for different thermal histories. The results obtained show that the amount of exudate varies in relation to the time that the sample needs to pass from -1 degrees C to -7 degrees C (characteristic freezing time). On the other hand, pH and concentration of proteins do not show significant differences between frozen and unfrozen samples. Similarly, neither one nor the other varies with the rate of freezing. The proteins were also analysed by electrophoresis in polyacrylamide gel. In this case, no differences were observed either between frozen samples and unfrozen ones or between samples which had been frozen at different rates. Hypotheses on the origin of cellular damage and alternatives which lead to the establishment of a standard of quality for quick frozen meat are presented in relation to the results obtained. PMID- 22055483 TI - Rapid determination of the 3-methylhistidine content of meat using 1-fluoro-2,4 dinitrobenzene. AB - The protein-bound 3-methylhistidine content of meat species has been shown to be of value in predicting the meat content of food products. The present paper deals with the development of a rapid method for the detection and estimation of the dinitrophenyl (DNP) derivatives of the methylamino acids and dipeptides, and in particular 3-methylhistidine. The DNP derivatives of methylated and non methylated basic amino acids and dipeptides were shown to have differing solubilities in diethyl ether and aqueous solution. These differences allowed preliminary purification of hydrolysed meat extracts, thereby allowing rapid determination of 3-methylhistidine using a short ion-exchange resin column. PMID- 22055484 TI - The practical application of 3-methylhistidine in determining the lean meat content of food products. AB - Protein-bound 3-methylhistidine, which is present at similar concentrations in various meat species but absent from non-meat proteins, was used to estimate the lean meat content of a range of retailed meat products. The results of the application of this novel method were compared and contrasted with those using standard methods of product analysis. The presence of textured soya protein in products was determined using polyacrylamide gel electrophoresis. Formulae for the calculation of the fat-free lean meat content on the bases of (i) the 3 methylhistidine index for muscle protein and (ii) the connective tissue content, are given. The lean meat contents of products calculated on these bases were found to be of the same order as, but generally lower than, those obtained using standard methods. This was considered to be due to the presence of non-meat proteins, of added connective tissue and/or certain types of offal. These would not be included in the lean meat content, as calculated by the 3-methylhistidine index, but could be legitimately included in the meat content calculated using standard methods according to current practice. A new interpretation of 'meat' in terms of 3-methylhistidine content is given. PMID- 22055485 TI - The effect of pressurisation of pre-rigor muscle on post-rigor meat characteristics. AB - Pressurisation of pre-rigor muscles produced very firm meat in muscles which had contracted to as little as 48% of their on-carcass length. Immediate post treatment pH was 5.81, significantly lower than the controls; however, there was no significant difference at 24 h. Water holding capacity of the treated samples was significantly lower and weep significantly higher than the controls. However, cooking losses for the treated samples were lower, resulting in an over-all loss which was not different between control and treated samples. Warner-Bratzler shear tests and taste panel evaluations indicate a highly significant improvement in tenderness. Scanning electron micrographs show an extensive disruption of the sarcolemma. PMID- 22055486 TI - Biochemical studies on fast glycolysing bovine muscle. AB - Of the psoas major muscles from 1395 carcasses of young bulls 64% showed pH(1) values (30 min post mortem) below 6.0. In 100 muscle samples (selected so that a normal distribution of the pH(1) values was obtained), water-holding capacity (WHC), brightness of colour and the concentration of all glycolytic metabolites were determined. There were correlations between pH(1) and the other characteristics of meat quality, lower pH(1) values were associated with lower WHC, paler colour, lower glycogen levels and higher levels of lactate (30 min post mortem). All these correlations were highly significant. The accelerated breakdown of glycogen-and a simultaneous accumulation of hexose monophosphates indicate an activation of the phosphorylase system in fast glycolysing bovine muscle. In fast glycolysing muscle, creatine phosphate was almost absent by 1 h post mortem and the ATP level was very low, indicating a high rate of breakdown of high-energy phosphates. The quality deviation of fast glycolysing beef is much less severe than that of PSE pork and therefore might not present a serious economic problem. PMID- 22055487 TI - The tenderising effect of electrical stimulation of beef carcasses. AB - Electrical stimulation (ES) of beef carcasses soon after death has an accelerated tenderising effect on the musculature, under conditions of slow cooling (8 h at 16 degrees C and then storage in still air at 1 degrees C). The effect is large in the LD muscles, reducing the shear force on day 1 of storage from 11 to 6 kg; on day 14, the difference is still 3.3 kg. These differences would be detected by taste panels. The St muscles show a similar, but less pronounced, effect which would probably not be detected by taste panels. The accelerated tenderisation due to ES can be accounted for by the higher temperatures obtaining in stimulated muscles at the onset of rigor. Rapid cooling soon after death reduces the effect almost to zero. Hence, the extra tenderisation cannot be due to muscle damage during ES. Histological examination shows that stimulated muscles have longer sarcomeres than the controls; they do not exhibit damage. However, with slow cooling, irregular bands of denatured sarcoplasmic protein are deposited within the fibres of stimulated muscles, similar to those found in PSE pig muscles. There is also some shortening of sarcomeres in the region of the bands. The protein is deposited on the myofibrillar surfaces. In spite of the PSE-like appearance, there is no significant increase in drip from the stimulated muscles at 48 h after death. PMID- 22055488 TI - Studies in electrical stimulation: Post-mortem decline in nervous response in lambs. AB - A study has been made of the effects of electrical stimulation, either indirectly through the nerves or directly through the muscles, on glycolysis in lamb hind leg muscles. Responses were affected by delay before application and the stimulating voltage. At 5 min post mortem the same fall in pH during stimulation (DeltapH) and subsequent increased rate of pH fall (dp H/dt) occurred in muscles stimulated both directly and indirectly with 12 V. With 200V, DeltapH was 50% greater in muscles stimulated directly and 30% less if stimulated indirectly. At 30 min post mortem there was very little effect of stimulation at either voltage on glycolysis when muscles were indirectly stimulated, indicating that the nerves had lost their capacity to trigger muscles to contract. In contrast, if the legs were stimulated directly, maximum DeltapH and dpH/dt values were achieved with 200 V pulses. The significance of these findings to the application of electrical stimulation to commercial meat processing is discussed. PMID- 22055489 TI - Removal of sodium dodecyl sulphate from complex with recovered offal proteins. PMID- 22055490 TI - Use of intramedullary nonvascularized fibular graft with external fixation for revisional Charcot ankle fusion: a case report. AB - We describe a case of Charcot ankle arthropathy in a 43-year-old male patient who underwent revision surgery for tibiotalocalcaneal arthrodesis with a retrograde intramedullary nonvascularized fibular graft. After 3 months of postoperative stabilization with a ring external fixator, successful radiographic union was identified. The findings obtained at 33 months postoperatively showed maintenance of solid fusion and restoration of hindfoot alignment without any complications. PMID- 22055491 TI - Radiofrequency thermoneurolysis for the treatment of Morton's neuroma. AB - Pedal neuroma is a common disorder. The authors undertook a review of 32 feet in 29 patients with a symptomatic neuroma treated between January 2007 and January 2010 to evaluate the effectiveness of radiofrequency thermoneurolysis therapy in alleviating symptoms. Overall relief of symptoms was rated as complete by 24 (83%) patients, with 5 patients experiencing minimal to no relief. Two patients were lost to follow-up after 1 month, 2 patients opted for no further intervention, and 1 patient went to open resection of the neuroma. Average follow up was 13 months and total recovery time was 2 days. Complications included 1 foot with cellulitis treated by a course of oral antibiotics. The results of this retrospective study indicate radiofrequency thermoneurolysis therapy is a safe, effective, and minimally invasive alternative treatment for symptomatic neuromas of the foot. PMID- 22055492 TI - Double row anchor fixation: a novel technique for a diabetic calanceal insufficiency avulsion fracture. AB - Avulsion fractures of the calcaneal tuberosity represent only 1.3% to 2.7% of calcaneal fractures. These fractures are common pathologically in nature and attributed to decreased bone mineral density. Calcaneal insufficiency avulsion (CIA) fracture in patients with diabetes mellitus is most likely due to Charcot neuroarthropathy (CN) as described by the Brodsky classification (Brodsky 3B). Traditional open reduction and internal fixation is difficult in all calcaneal avulsion fractures because of poor bone quality. The authors report the first known description of the use of fracture fragment excision and double row anchor fixation.A 39-year-old woman with type I diabetes mellitus and a history of CN presented with an avulsion fracture of the calcaneal tuberosity. Excision of the fracture fragment and a gastrocnemius recession and reattachment of the Achilles tendon with double row anchor fixation to the calcaneus were performed. At 1 year, the patient's American Orthopaedic Foot & Ankle Society rearfoot score improved from 27/100 to 88/100. CIA fractures are an infrequently described injury. Because diabetes mellitus is frequently associated with this disease, it most likely represents a CN event. Traditionally, CIA fractures have been operatively treated with open reduction internal fixation. Previous authors have described difficulty with fixation because of poor quality. In the current report, the authors describe a novel operative approach to CIA fractures through the use of double row anchor fixation and excision of the fracture fragments. The authors feel that this previously undescribed treatment is superior to traditional methods and may serve as a new treatment option for all patients who have sustained this unusual pathology regardless of the underlying cause. The current authors provide a novel operative technique that provides inherent advantages to the traditional repair of CIA fractures. We believe CIA fractures represent a CN-type event and care should be taken when evaluating and treating these patients to prevent further sequelae. PMID- 22055493 TI - A case of "fresh rupture" after open repair of a ruptured Achilles tendon. AB - We present the case of Achilles tendon rupture in a 54-year-old man while rehabilitating after end-to-end open repair of an acute Achilles tendon rupture. Re-rupture after surgical repair of Achilles tendon is well known. The present case, however, is atypical, because the second rupture occurred significantly proximal to the first rupture. To our knowledge, this is the first time this has been described in English language studies. We have termed this incident a fresh rupture. A gastrocnemius turndown flap was used to repair the fresh rupture, which led to a satisfactory recovery. This case report serves to inform surgeons of the existence of this type of Achilles tendon rupture, while considering the possible etiologies and suggesting a technique that has been shown to be successful in the present case. PMID- 22055494 TI - Quantum dots find their stride in single molecule tracking. AB - Thirteen years after the demonstration of quantum dots as biological imaging agents, and nine years after the initial commercial introduction of bioconjugated quantum dots, the brightness and photostability of the quantum dots has enabled a range of investigations using single molecule tracking. These materials are being routinely utilized by a number of groups to track the dynamics of single molecules in reconstituted biophysical systems and on living cells, and are especially powerful for investigations of single molecules over long timescales with short exposure times and high pointing accuracy. New approaches are emerging where the quantum dots are used as 'hard-sphere' probes for intracellular compartments. Innovations in quantum dot surface modification are poised to substantially expand the utility of these materials. PMID- 22055495 TI - Label-free optical imaging of nonfluorescent molecules by stimulated radiation. AB - Imaging contrasts other than fluorescence are highly desirable for label-free detection and interrogation of nonfluorescent molecular species inside live cells, tissues, and organisms. The recently developed stimulated Raman scattering (SRS) and stimulated emission microscopy techniques provide sensitive and specific contrast mechanisms for nonfluorescent species, by employing the light amplification aspect of stimulated radiation. Compared to their spontaneous counterparts, stimulated radiation can enhance the imaging performance significantly, making the previously 'dark' molecules observable. Here we review and summarize the underlying principles of this emerging class of molecular imaging techniques. PMID- 22055496 TI - Imaging of RNA in live cells. AB - Fluorescence microscopy and molecular tagging technologies have ushered in a new era in our understanding of protein localization and function in cells. This review summarizes recent efforts to extend some of these methods (and to create new ones) to imaging of RNA in live cells. Both fluorescent proteins and hybridization probes allow noncovalent labeling of specific RNA molecules with fluorescent dyes that allow detection and tracking in real time. PMID- 22055497 TI - Diversity-oriented optical imaging probe development. AB - The development of optical probes is receiving considerable attention due to their rising adaptation in diagnostics and medical imaging. Diversity-oriented approaches make use of combinatorial chemistry and high-throughput screenings to enrich the spectral and structural variety of these probes and effectively identify those with specific properties (e.g. molecular affinity, cellular selectivity, high photostability, and sensitivity). Herein we review recent examples in which diversity-driven strategies have assisted the discovery of new molecular imaging probes. PMID- 22055498 TI - In and out: adipose tissue lipid turnover in obesity and dyslipidemia. AB - Adipose tissue is the main site of storage and mobilization of lipid. In a recent study published in Nature, Arner et al. (2011) report that high storage and low removal of adipose triglycerides promotes obesity, whereas low storage and low removal favor the development of dyslipidemia in humans. PMID- 22055499 TI - A PGC-1 tale: healthier intestinal stem cells, longer life. AB - PGC-1 regulates energy homeostasis and mitochondrial activity. In this issue, Rera et al. (2011) show that dPGC-1 overexpression in Drosophila intestinal stem cells and their immediate progeny extends organismal life span and protects against age-related loss of intestinal homeostasis and integrity, thereby establishing a link between mitochondria, tissue stem cells, and aging. PMID- 22055500 TI - Setting the tone: reactive oxygen species and the control of appetitive melanocortin neurons. AB - The brain melanocortin system is a primary gateway through which energy balance is controlled. Diano and colleagues report a novel cellular mechanism mediated via reactive oxygen species (ROS) that regulates the activity of these melanocortin neurons in response to energy status, thereby modulating appetitive behavior (Diano et al., 2011). PMID- 22055501 TI - Insulin resistance, hyperglycemia, and atherosclerosis. AB - Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role of hyperglycemia in CAD associated with type 2 diabetes is less clear. Understanding the mechanisms whereby type 2 diabetes exacerbates CAD offers hope for new therapeutic strategies to prevent and treat atherosclerotic vascular disease. PMID- 22055502 TI - Dissociation of the glucose and lipid regulatory functions of FoxO1 by targeted knockin of acetylation-defective alleles in mice. AB - FoxO1 integrates multiple metabolic pathways. Nutrient levels modulate FoxO1 acetylation, but the functional consequences of this posttranslational modification are unclear. To answer this question, we generated mice bearing alleles that encode constitutively acetylated and acetylation-defective FoxO1 proteins. Homozygosity for an allele mimicking constitutive acetylation (Foxo1(KQ/KQ)) results in embryonic lethality due to cardiac and angiogenesis defects. In contrast, mice homozygous for a constitutively deacetylated Foxo1 allele (Foxo1(KR/KR)) display a unique metabolic phenotype of impaired insulin action on hepatic glucose metabolism but decreased plasma lipid levels and low respiratory quotient that are consistent with a state of preferential lipid usage. Moreover, Foxo1(KR/KR) mice show a dissociation between weight gain and insulin resistance in predisposing conditions (high fat diet, diabetes, and insulin receptor mutations), possibly due to decreased cytokine production in adipose tissue. Thus, acetylation inactivates FoxO1 during nutrient excess whereas deacetylation selectively potentiates FoxO1 activity, protecting against excessive catabolism during nutrient deprivation. PMID- 22055503 TI - PPARalpha-Sirt1 complex mediates cardiac hypertrophy and failure through suppression of the ERR transcriptional pathway. AB - High energy production in mitochondria is essential for maintaining cardiac contraction in the heart. Genes regulating mitochondrial function are commonly downregulated during heart failure. Here we show that both PPARalpha and Sirt1 are upregulated by pressure overload in the heart. Haploinsufficiency of either PPARalpha or Sirt1 attenuated pressure overload-induced cardiac hypertrophy and failure, whereas simultaneous upregulation of PPARalpha and Sirt1 exacerbated the cardiac dysfunction. PPARalpha and Sirt1 coordinately suppressed genes involved in mitochondrial function that are regulated by estrogen-related receptors (ERRs). PPARalpha bound and recruited Sirt1 to the ERR response element (ERRE), thereby suppressing ERR target genes in an RXR-independent manner. Downregulation of ERR target genes was also observed during fasting, and this appeared to be an adaptive response of the heart. These results suggest that suppression of the ERR transcriptional pathway by PPARalpha/Sirt1, a physiological fasting response, is involved in the progression of heart failure by promoting mitochondrial dysfunction. PMID- 22055504 TI - Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. AB - Resveratrol is a natural compound that affects energy metabolism and mitochondrial function and serves as a calorie restriction mimetic, at least in animal models of obesity. Here, we treated 11 healthy, obese men with placebo and 150 mg/day resveratrol (resVida) in a randomized double-blind crossover study for 30 days. Resveratrol significantly reduced sleeping and resting metabolic rate. In muscle, resveratrol activated AMPK, increased SIRT1 and PGC-1alpha protein levels, increased citrate synthase activity without change in mitochondrial content, and improved muscle mitochondrial respiration on a fatty acid-derived substrate. Furthermore, resveratrol elevated intramyocellular lipid levels and decreased intrahepatic lipid content, circulating glucose, triglycerides, alanine aminotransferase, and inflammation markers. Systolic blood pressure dropped and HOMA index improved after resveratrol. In the postprandial state, adipose tissue lipolysis and plasma fatty acid and glycerol decreased. In conclusion, we demonstrate that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. PMID- 22055505 TI - Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. AB - In mammals, the PGC-1 transcriptional coactivators are key regulators of energy metabolism, including mitochondrial biogenesis and respiration, which have been implicated in numerous pathogenic conditions, including neurodegeneration and cardiomyopathy. Here, we show that overexpression of the Drosophila PGC-1 homolog (dPGC-1/spargel) is sufficient to increase mitochondrial activity. Moreover, tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract extends life span. Long-lived flies overexpressing dPGC-1 display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homeostasis in old flies. Together, these results demonstrate that dPGC-1 can slow aging both at the level of cellular changes in an individual tissue and also at the organismal level by extending life span. Our findings point to the possibility that alterations in PGC-1 activity in high-turnover tissues, such as the intestine, may be an important determinant of longevity in mammals. PMID- 22055506 TI - Activation of the HIF prolyl hydroxylase by the iron chaperones PCBP1 and PCBP2. AB - Mammalian cells express dozens of iron-containing proteins, yet little is known about the mechanism of metal ligand incorporation. Human poly (rC) binding protein 1 (PCBP1) is an iron chaperone that binds iron and delivers it to ferritin, a cytosolic iron storage protein. We have identified the iron-dependent prolyl hydroxylases (PHDs) and asparaginyl hydroxylase (FIH1) that modify hypoxia inducible factor alpha (HIFalpha) as targets of PCBP1. Depletion of PCBP1 or PCBP2 in cells led to loss of PHD activity, manifested by reduced prolyl hydroxylation of HIF1alpha, impaired degradation of HIF1alpha through the VHL/proteasome pathway, and accumulation of active HIF1 transcription factor. PHD activity was restored in vitro by addition of excess Fe(II), or purified Fe PCBP1, and PCBP1 bound to PHD2 and FIH1 in vivo. These data indicated that PCBP1 was required for iron incorporation into PHD and suggest a broad role for PCBP1 and 2 in delivering iron to cytosolic nonheme iron enzymes. PMID- 22055507 TI - Classification of trace patterns of 226- and 1000-Hz tympanometry in healthy neonates. AB - OBJECTIVE: Accurate evaluation of middle ear function is a challenge especially in babies referred from newborn hearing screening programs. The aim was to assess the feasibility of tympanometry using 226- and 1000-Hz probe tones in neonates. METHODS: Hearing was evaluated by transient evoked otoacoustic emission (TEOAE) in 96 ears of healthy neonates in well-baby nursery. Babies with risk factors for hearing loss as identified in Joint Committee on Infant Hearing (JCIH, 1994) were excluded. Tympanograms recorded with 226 and 1000Hz probe tones were analyzed and classified. RESULTS: Tympanograms were classified according to Method A (Jerger/Liden) and visual classification systems, Method B (adapted from Marchant et al.) and Method C (adapted from Kei et al.), without difficulty. In 72 ears with normal TEOAE, 226Hz tympanograms were classified as normal in 72 ears in Methods A and B, and 16 ears in Method C. 1000Hz tympanograms were normal in 68 ears in Method A, 72 ears in Method B and 68 ears in Method C. In 24 ears with abnormal TEOAE, 226Hz tympanograms were interpreted as normal in most ears (23 ears in Method A, 24 ears in Method B), whereas 1000Hz tympanograms were abnormal in 13 ears in Method A and 6 ears in Method B, possibly reflecting middle ear dysfunction. CONCLUSION: In healthy neonates without risk factors for hearing loss, 1000Hz tympanograms can be recorded and interpreted. A single-peaked tympanograms was most common in ears with normal TEOAE. In ears with abnormal TEOAE, tympanograms were classified as abnormal more frequently using 1000Hz than 226Hz. Implementation of tympanometry using 1000Hz probe tone in newborn hearing screening programs may provide valuable information regarding middle ear dysfunction that may cause transient conductive hearing loss. PMID- 22055508 TI - Immunohistochemical and biomolecular identification of melatonin 1a and 1b receptors in rat vestibular nuclei. AB - OBJECTIVE: The aim of this study was to examine the localizations and expressions of melatonin 1a (MT1a) and 1b (MT1b) receptors in rat vestibular nuclei by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. MATERIALS AND METHODS: Twenty male Sprague-Dawley rats were used in this study. Antibodies for the MT1a and MT1b receptors were used in 10 rats, respectively. A further 10 animals were sacrificed for RT-PCR. Tissues containing medial vestibular nuclei were selectively isolated from brain stem slices for RT-PCR. RESULTS: MT1a and MT1b receptor immunopositive neurons were found to be distributed throughout the four major vestibular nuclei. Both receptors were primarily detected in neuronal somata and their proximal dendrites. The presences of the mRNAs of the MT1a and MT1b receptors were confirmed by RT-PCR in medial vestibular nuclei and trigeminal ganglia. CONCLUSIONS: The present study demonstrates, for the first time, that MT1a and MT1b receptors are localized and expressed in rat vestibular nuclei. This study provides additional insight into the role of melatonin receptors during vestibular signal processing. PMID- 22055509 TI - Radiological analysis of the ethmoid roof in the Malaysian population. AB - OBJECTIVE: To ascertain the prevalence of the lateral lamella of the cribriform plate height according to Keros classification in the Malaysian population, and to find if there is any difference between the major ethnic groups in Malaysia (Malay, Chinese, Indian). METHODS: Retrospective analysis of 150 CT scan studies of the paranasal sinuses. RESULTS: The mean height of the lateral lamella of the cribriform plate (LLCP) in 300 sides was 2.64mm. Keros type I was seen in 240 sides (80%), while, Keros type II was seen in 60 sides (20%). There was no significant difference in the distribution of Keros classification among the major ethnic groups of Malaysia (Malay, Chinese, Indian). Keros type I was seen in 103 sides in males and 137 sides in females. Significant difference was observed in type II between the male and female (47 sides in males and 13 sides in female; p-value <0.001). When comparing the difference in the height of the LLCP in the same individual, asymmetry was observed in 139 patients. The LLCP height was higher on the left side in 71 patients and higher on the right in 68. CONCLUSION: The understanding of the anatomy of the ethmoid roof with its possible variation is crucial to give the surgeon the optimal information about the possible risk that one can face during the surgery. PMID- 22055510 TI - Colour and colour stability of hot processed frozen minced beef. Results from chemical model experiments tested under storage conditions. AB - Minced beef based on hot processed meat was found to show an improved red colour and, more significantly, to show a better colour stability with respect to brown discoloration, when compared to minced beef resulting from a traditional (cold) process. The colour was followed by tristimulus colorimetry during freezer storage (product temperature -18 degrees C) in a display cabinet illuminated by fluorescent tubes. The development of brown discoloration seems to indicate other oxidative changes and to relate to rancidity as judged from a determination of thiobarbituric acid reactive substances in the mince surface. Fluorescent light and added salt, both known from chemical models to increase the autoxidation rate of red oxymyoglobin to brown metmyoglobin, greatly reduced the colour stability, especially for cold deboned meat. pH of the hot deboned meat was significantly higher (pH > 6.0) than that of the cold deboned meat (pH ranged from 5.5 to 5.8). The observations are discussed in relation to kinetic salt effect on the acid catalyzed autoxidation of oxymyoglobin and its role in the initiation of oxidative rancidity. PMID- 22055511 TI - Proteinase (Cathepsin B, D, L and Calpains) levels and conditioning rates in normal, electrically stimulated and high-ultimate-pH chicken muscle. AB - Control, electrically stimulated (ES) and glycogen-depleted (GD) chicken muscles were conditioned at 15 degrees C with continuous mechanical testing for extensibility. The ES and GD muscles went into rigor 3.6 and 2.8 h earlier, respectively, than control muscle. At 24h post-rigor the extensibility of control muscle (11.2%) was markedly less than ES (19.2%) and GD (27.3%) muscles indicating that these latter two treatments should provide more tender meat. Measurement of sarcomere lengths showed no significant differences between control and GD muscle and thus, the greater extensibility in the high pH condition may be restricted to a wider separation of myofibriller fragments at the intermittent fracture zones when under load. Examination of muscle proteinase (cathepsins B, D and L, calpains I and II) and glycosidase (beta-d-glucuronidase, N-acetyl-beta-d-glucosaminidase) levels at 0 and 48h post-slaughter revealed changes in some key enzymes between the different treatments. Calpain I activity declined markedly during 48h storage of ES muscle (83%) compared to control (58%) and GD (63%) muscles. Cathepsin B and L activities did not decline during storage of ES muscle but there was a slight fall in control and GD muscles. Dosing of chicken shortly before slaughter with inhibitors of cysteine proteinases had a negligible effect on conditioning rate, apparently due to lack of inhibition of these proteinases during this short time period in the intact muscle. PMID- 22055512 TI - Analysis of proteolysis and protein insolubility during the manufacture of some varieties of dry sausage. AB - Proteolysis and protein insolubility were studied during the curing of dry sausages such as chorizo, saucisson and salami. Sausages prepared using a meat cutter showed more proteolysis and less protein insolubility in comparison to those prepared using a mincer. Insolubilisation caused a loss in both sarcoplasmic and myofibrillar solubility distinctive for each type of sausage. PMID- 22055513 TI - Progress towards using the speed of ultrasound for beef leanness classification. AB - Following the observation of a high correlation between the reciprocal of the speed of ultrasound and lean proportion in beef carcasses, commercial equipment (VOSI) was developed and its performance alongside a smaller assembly (Mini G) is reported. The speed of ultrasound was measured through six sites on beef carcasses within 1 h of stunning: three sites with VOSI and three sites with Mini G. Sides were also scored for fatness and conformation using the EAAP system, and subcutaneous fat depth was measured at 25,50 and 75% of the width of M. longissimus thoracis from the midline at the last rib. All sides were dissected into subcutaneous fat, intermuscular fat, muscle and bone. The reciprocal speed averaged over the three VOSI sites (RV346) was the best single predictor of the proportion of lean in the side. Multiple regression analyses, in predicting per cent lean, showed that addition of conformation score improved the precision of fat score and fat depth for a group of 26 sides. It did not provide a significant improvement over RV346. However, in another group of 50 sides showing more variation in side mass and conformation, conformation score did significantly improve RV346. The best prediction of per cent lean, involving RV346 and tissue thicknesses, gave a residual standard deviation of 1.35%, and conformation score did not significantly improve this regression. PMID- 22055514 TI - The effects of withholding feed and water on carcass shrinkage and meat quality in beef cattle. AB - Eighty beef crossbred steers with an average weight of 493 kg (4.66 kg SD) were allocated at random to one of five treatments to assess the effects of withholding feed and water on carcass shrinkage and meat quality. The five treatments were: slaughter from the feedlot (T1); and 12, 24, 36 and 48 h periods without feed and water prior to slaughter (T2-5).Weights were taken of the live animal and the carcass to monitor shrinkage along with relevant meat quality measurements. There were no treatment differences (P > 0.05) in initial farm weight, but plant weight shrinkage increased from 31gkg(-1) for T1 to 106 g kg( 1) for T5. Warm carcass weight decreased (P < 0.05) from 278.8 kg for T1, to 270.7 kg for T3 and 261.9 kg for T5. Liver, alimentary tract components, hide and head decreased as a proportion of farm weight as time without feed and water increased. Muscle pH at 6 days post mortem was increased (P < 0.05) in T3-5 compared to T1, with the result that muscle colour became darker, and steaks had less drip loss. Shear values increased (P < 0.05) from 6.3 kg in T1 to 7.7 kg in T4 and T5 indicating an increase in muscle toughness as time without feed and water increased. It was concluded that steers lose live weight rapidly within the first 24 h without feed and water, and that these relatively short periods of time (24 h) can have detrimental effects on carcass shrinkage and muscle quality. PMID- 22055515 TI - The influence of varying degrees of adhesion as determined by mechanical tests on the sensory and consumer acceptance of a meat product. AB - The adhesion between meat pieces in meat products, varied by the addition of different concentrations of a crude myosin solution, was measured by a trained sensory panel and by two instrumental tests: tensile adhesive strength (TAS) and punch and die. A consumer trial was used to find which level of adhesion was preferred. Results from the sensory panel showed that the adhesion could be detected as highly significant (P < 0.001) differences in three tactile measurements and in the two eating qualities, ease of fragmentation and rubberines. TAS measurements gave larger differences between treatments than punch and die, and had very high correlations with ease of fragmentation and crumblines on cutting. The small consumer study revealed no overall preference for any one product. Hence, although differences in adhesion between meat pieces in a meat product are detectable subjectively and can be measured objectively by TAS tests, preference for any particular strength varies between individuals. PMID- 22055516 TI - Psychophysical investigations into the tenderness of meat. AB - Tenderness of five veal meat cuts was determined by two groups of subjects: a panel of skilled butchers and a consumers' panel. The butchers estimated tenderness with and without assistance of visual information. For the consumers a procedure to measure the oral sensation by a forced choice method of successive comparison was developed. It was shown that: imprecision of the opinions of the consumers was greater than that of the butchers; use of additional visual information did not affect the butchers' precision; and the butchers' views of tenderness had a poor relationship to the consumers' oral perception of this quality. PMID- 22055517 TI - Characteristics of pork products from swine fed a high monounsaturated fat diet: Part 3-A high-fat cured product. AB - Fresh pork bellies from animals fed a control sorghum-soybean diet and a similar diet containing 12% high-oleic sunflower oil (HOSO) were cured and processed in a smokehouse to an internal temperature of 55.6 degrees C. Cooking losses were not significantly different (p < 0.05) between bacon strips from animals on the control diet and those from animals on the HOSO diet. The ratio of monounsaturated fatty acids to saturated fatty acids for the cooked rasher from the HOSO group was 1.84 times that for the cooked rasher from the control group (2.48 versus 1.35). The cooked rasher had a slightly lower (p < 0.05) percentage of total monosaturates that uncooked bacon strips within each diet group. When considering stearic acid as a fatty acid that does not raise the plasma cholesterol level in the human, along with all unsaturated fatty acids, only 16.83% and 12.26% of total fatty acids in the cooked rasher and the drip, respectively, from the HOSO group were fatty acids (C14:0 and C16:0) which may raise the plasma cholesterol level. The residual nitrite level in the raw and cooked bacon was higher (P < 0.05) for samples from the HOSO group than for those from the control group, probably due to binding of nitrite to the double bonds in unsaturated fatty acids that were higher for samples from the HOSO group. The extent of the accumulation of thiobarbituric acid-reactive substances during frozen storage was not affected (P > 0.05) by the inclusion of 12% HOSO in the animal diet, regardless of the packaging method. PMID- 22055518 TI - Surfactant addition and alternating current electrophoretic oscillation during size fractionation of nanoparticles in channels with two or three different height segments. AB - An array of parallel planar nanochannels containing two or three segments with varying inner heights was fabricated and used for size fractionation of inorganic and biological nanoparticles. A liquid suspension of the particles was simply drawn through the nanochannels via capillary action. Using fluorescently labeled 30 nm polyacrylonitrile beads, different trapping behaviors were compared using nanochannels with 200-45 nm and 208-54-30 nm height segments. Addition of sodium dodecyl sulfate (SDS) surfactant to the liquid suspension and application of an AC electric field were shown to aid in the prevention of channel clogging. After initial particle trapping at the segment interfaces, significant particle redistribution occurred when applying a sinusoidal 8V peak-to-peak oscillating voltage with a frequency of 150 Hz and DC offset of 4V. Using the 208-54-30 nm channels, 30 nm hepatitis B virus (HBV) capsids were divided into three fractions. When the AC electric field was applied to this trapped sample, all of the virus particles passed through the interfaces and accumulated at the channel ends. PMID- 22055519 TI - Comparison of the quantitative performance of constant pressure versus constant flow rate gradient elution separations using concentration-sensitive detectors. AB - This contribution discusses the difference in chromatographic performance when switching from the customary employed constant flow rate gradient elution mode to the recently re-introduced constant pressure gradient elution mode. In this mode, the inlet pressure is maintained at a set value even when the mobile phase viscosity becomes lower than the maximum mobile phase viscosity encountered during the gradient program. This leads to a higher average flow rate compared to the constant flow rate mode and results in a shorter analysis time. When both modes carry out the same mobile phase gradient program in volumetric units, normally identical selectivities are obtained. However, small deviations in selectivity are found due to the differences in pressure and viscous heating effects. These selectivity differences are of the same type as those observed when switching from HPLC to UHPLC and are inevitable when speeding up the analysis by applying a higher pressure. It was also found that, when using concentration-sensitive detectors, the constant pressure elution mode leads to identical peak areas as the constant flow rate mode. Also the linearity is maintained. In addition, the repeatability of the peak area and retention time remains the same when switching between both elution modes. PMID- 22055520 TI - Study of the interdependency of the data sampling ratio with retention time alignment and principal component analysis for gas chromatography. AB - An in-depth study is presented to better understand how data reduction via averaging impacts retention alignment and the subsequent chemometric analysis of data obtained using gas chromatography (GC). We specifically study the use of signal averaging to reduce GC data, retention time alignment to correct run-to run retention shifting, and principal component analysis (PCA) to classify chromatographic separations of diesel samples by sample class. Diesel samples were selected because they provide sufficient complexity to study the impact of data reduction on the data analysis strategies. The data reduction process reduces the data sampling ratio, S(R), which is defined as the number of data points across a given chromatographic peak width (i.e., the four standard deviation peak width). Ultimately, sufficient data reduction causes the chromatographic resolution to decrease, however with minimal loss of chemical information via the PCA. Using PCA, the degree of class separation (DCS) is used as a quantitative metric. Three "Paths" of analysis (denoted A-C) are compared to each other in the context of a "benchmark" method to study the impact of the data sampling ratio on preserving chemical information, which is defined by the DCS quantitative metric. The benchmark method is simply aligning data and applying PCA, without data reduction. Path A applies data alignment to collected data, then data reduction, and finally PCA. Path B applies data reduction to collected data, and then data alignment, and finally PCA. The optimized path, namely Path C, is created from Paths A and B, whereby collected data are initially reduced to fewer data points (smaller S(R)), then aligned, and then further reduced to even fewer points and finally analyzed with PCA to provide the DCS metric. Overall, following Path C, one can successfully and efficiently classify chromatographic data by reducing to a S(R) of ~15 before alignment, and then reducing down to S(R) of ~2 before performing PCA. Indeed, following Path C, results from an average of 15 different column length-with-temperature ramp rate combinations spanning a broad range of separation conditions resulted in only a ~15% loss in classification capability (via PCA) when the loss in chromatographic resolution was ~36%. PMID- 22055521 TI - On-line coupling of a clean-up device with supported liquid membrane to capillary electrophoresis for direct injection and analysis of serum and plasma samples. AB - A simple sample clean-up device with planar supported liquid membrane (SLM) was developed and coupled on-line to capillary electrophoresis (CE) for direct injection of human body fluids. Donor and acceptor compartments of the device were filled with diluted body fluid and deionized water, respectively, and the two solutions were separated by a thin SLM. Analytes of interest were selectively transported from the donor solution through the SLM into the acceptor solution by diffusion whereas interfering matrix components were efficiently retained on the SLM. Equilibrium between the concentrations of analytes at the SLM was obtained typically in 5 min. Then a CE separation capillary was inserted into the acceptor compartment to firmly touch the SLM and the pretreated sample was hydrodynamically injected into the capillary. The analytical procedure was demonstrated by rapid pretreatment, on-line injection, and CE determination of selected amino acids in human serum and plasma samples. 1-Ethyl-2-nitrobenezene and bis(2-ethylhexyl) phosphate (15%, v/v) was used as the selective SLM for clean-up of the body fluids and 0.5M acetic acid was used as a background electrolyte solution for CE analysis of the pretreated amino acids. Concentrations of amino acids on acceptor side of the SLM reached 40-58% of their original concentrations in donor solution after 5 min equilibration time and then remained constant proving that equilibrium was achieved at the SLM. Injection of the pretreated samples was highly repeatable with RSD values of peak areas 2.4 8.4% and 3.4-10.5% for standard solutions and real samples, respectively. Limits of detection between 0.75 and 2.5 MUM were achieved, corresponding to 3.75-12.5 MUM in 1:4 diluted real samples, which ensure sensitive determination of most amino acids in the body fluids. The developed method is fast, simple, efficient, cheap and selective and may be applied to determination of a wide range of analytes in various samples with complex matrices. PMID- 22055522 TI - Development of a nano-liquid chromatography on chip tandem mass spectrometry method for high-sensitivity hepcidin quantitation. AB - Microfluidic LC systems present undeniable advantages over classical LC in terms of sensitivity. Hepcidin, a peptide marker of clinical disorders linked to iron metabolism, was used as model to demonstrate peptide quantification potentialities of LC-chip coupled to a nanoelectrospray source ion trap mass spectrometer in an aqueous sample. First, stable isotope labelled hepcidin was chosen as internal standard and gradient as well as sample compositions were optimised using design of experiments as development tool. The method was then prevalidated using accuracy profiles in order to select the most appropriate response function and to confirm the ability of the technique to quantify low hepcidin concentration. A reliable and very sensitive quantitation method was finally obtained using this integrated microfluidic technology. Indeed, good results with respect to accuracy, trueness and precision were achieved, as well as a very low limit of quantitation (0.07 ng/ml). Method suitability of nano-LC on chip tandem mass spectrometry for hepcidin quantitation was also demonstrated in complex media such as human plasma. PMID- 22055523 TI - Development and evaluation of needle trap device geometry and packing methods for automated and manual analysis. AB - For air/headspace analysis, needle trap devices (NTDs) are applicable for sampling a wide range of volatiles such as benzene, alkanes, and semi-volatile particulate bound compounds such as pyrene. This paper describes a new NTD that is simpler to produce and improves performance relative to previous NTD designs. A NTD utilizing a side-hole needle used a modified tip, which removed the need to use epoxy glue to hold sorbent particles inside the NTD. This design also improved the seal between the NTD and narrow neck liner of the GC injector; therefore, improving the desorption efficiency. A new packing method has been developed and evaluated using solvent to pack the device, and is compared to NTDs prepared using the previous vacuum aspiration method. The slurry packing method reduced preparation time and improved reproducibility between NTDs. To evaluate the NTDs, automated headspace extraction was completed using benzene, toluene, ethylbenzene, p-xylene (BTEX), anthracene, and pyrene (PAH). NTD geometries evaluated include: blunt tip with side-hole needle, tapered tip with side-hole needle, slider tip with side-hole, dome tapered tip with side-hole and blunt with no side-hole needle (expanded desorptive flow). Results demonstrate that the tapered and slider tip NTDs performed with improved desorption efficiency. PMID- 22055524 TI - Fluorosurfactant-prepared triangular gold nanoparticles as postcolumn chemiluminescence reagents for high-performance liquid chromatography assay of low molecular weight aminothiols in biological fluids. AB - Our recent study demonstrates the synthesized triangular gold nanoparticles (AuNPs) by trisodium citrate reduction of HAuCl(4) in the presence of nonionic fluorosurfactant (FSN) could display stronger catalytic activity towards luminol chemiluminescence (CL) than spherical AuNPs. Ultratrace aminothiols may cause a great decrease in CL intensity of the triangular AuNPs-luminol CL system. In this article, we utilize the as-prepared triangular AuNPs as novel postcolumn CL reagents to explore a simple high-performance liquid chromatography (HPLC)-CL method for the determination of low molecular weight aminothiols (i.e., cysteine, homocysteine, glutathione, cysteinylglycine and glutamylcysteine). The as prepared triangular AuNPs were easier to synthesize, stable at a wider pH range and high ionic strength, and highly selective and sensitive towards reduced aminothiols. The detection limits at a signal-to-noise ratio of 3 for cysteine, homocysteine, glutathione, cysteinylglycine and glutamylcysteine were 0.016, 0.08, 0.1, 0.04 and 0.1pmol, respectively. Recoveries from spiked urine and plasma samples were 95.7-104.3%. The applicability of the proposed method has been validated by determining these low molecular weight aminothiols in human urine and plasma samples with satisfactory results, and thus it will have great potential application in clinical diagnosis. PMID- 22055525 TI - Closed loop control of the multi-column solvent gradient purification process. AB - A PID controller able to support the operator in the operation of the Multi column Countercurrent Solvent Gradient Purification (MCSGP) process which is a continuous, countercurrent chromatographic process has been developed. As measurement, only the online UV signals at each column outlet are used. This guarantees a simple and cheap control implementation and a fast control action. Accordingly, the controller does not guarantee any purity or yield value, but simply that the withdrawn window of the product is centered in a specific region of the UV chromatogram where the purity specifications are expected to be satisfied. This can be determined by the operator based on the batch chromatogram selected for designing the MCSGP operating conditions. Thus the controller provides a reliable and efficient tool for the operator to run properly a MCSGP unit in combination with suitable offline analytics for the quantification of purity and yield. The applications are discussed involving the purification of a model protein and a peptide. It is shown that the developed controller is effective in driving the unit to steady state during start up and in keeping a stable steady state while rejecting external disturbances. PMID- 22055526 TI - Application of different modes of thin-layer chromatography and mass spectrometry for the separation and detection of large and small biomolecules. AB - Biomolecules are widespread throughout the world. A biomolecule is any organic molecule produced by a living organism, including large polymeric molecules such as proteins, polysaccharides and nucleic acids. Many sample preparation techniques are used in biomolecule analysis; the method selected depends on the complexity of the sample, the nature of the matrix and the analytes, and the analytical technique available. This review covers the current state of knowledge on thin-layer chromatography and mass spectrometry for qualitative analysis of biomolecules. In the first part of the paper the reader will gain useful information to avoid some problems about performing various modes of thin-layer chromatography combined with mass spectrometry experiments and in the second part he will find useful information for application of these techniques for separation, detection, and qualitative investigation of structures and quantitative determination of biomolecules such as proteins, peptides, oligonucleotides, amino acids, DNA, RNA, and lipids. PMID- 22055527 TI - The circular economy and its risks. PMID- 22055529 TI - Antimicrobial susceptibility of Escherichia coli from community-acquired urinary tract infections in Europe: the ECO.SENS study revisited. AB - This study determined the antimicrobial susceptibility of Escherichia coli causing community-acquired, acute, uncomplicated, non-recurrent urinary tract infection in unselected women aged 18-65 years and compared the results with those obtained 8 years earlier in the first ECO.SENS study (1999-2000). During 2007-2008, urine samples were taken from 1697 women in Austria, Greece, Portugal, Sweden and the UK. The countries were chosen to represent areas of Europe indicated to have more (Greece and Portugal) or less (UK, Austria and Sweden) problems with resistance. Antimicrobial susceptibility testing of 903 E. coli isolates (150-200 isolates per country) to 14 antimicrobials was performed by disk diffusion using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. In E. coli, resistance to mecillinam, cefadroxil (representing oral cephalosporins), nitrofurantoin, fosfomycin trometamol, gentamicin and the third-generation cephalosporins cefotaxime and ceftazidime was <2%, with the following exceptions: gentamicin in Portugal (2.8%); fosfomycin in Greece (2.9%); and cephalosporins in Austria (2.7-4.1%). Resistance levels were higher for amoxicillin/clavulanic acid (2.0-8.9%) and ciprofloxacin (0.5-7.6%) and much higher to ampicillin (21.2-34.0%), sulfamethoxazole (21.2-31.3%), trimethoprim (14.9-19.1%) and trimethoprim/sulfamethoxazole (14.4-18.2%). Resistance to quinolones and trimethoprim increased between the ECO.SENS I (1999 2000) and ECO.SENS II (2007-2008): nalidixic acid 4.3% to 10.2%; ciprofloxacin 1.1% to 3.9%; and trimethoprim 13.3% to 16.7%. In the previous study, no isolates with extended-spectrum beta-lactamase were found; however, in the present study 11 isolates were identified as having either CTX-M or AmpC. PMID- 22055530 TI - Molecular epidemiology and mechanisms of rifampicin resistance in Acinetobacter baumannii isolates from Italy. AB - Use of rifampicin (RIF) in combination with colistin (COL) has been proposed for the treatment of multidrug-resistant Acinetobacter baumannii infections owing to in vitro synergism. The aim of the present study was to evaluate the molecular epidemiology and mechanisms of RIF resistance in 57 clinical isolates of A. baumannii in two tertiary care hospitals in Naples (Italy) from 2006 to 2010. Amongst the collection, 36 isolates showed high RIF minimum inhibitory concentrations (MICs) (256 mg/L to >=512 mg/L), 16 showed intermediate MICs (8-16 mg/L) and 5 had low MICs (4 mg/L). Of the 36 isolates with elevated RIF MICs, 35 were assigned to sequence type ST2 and 1 to ST78. Amongst the 57 isolates, 35 carried at least one mutation in rpoB, including H535L in 9 isolates and double mutations D525N and P544L in 7 isolates, whilst 22 showed no rpoB mutations. Treatment with the efflux pump inhibitor phenyl-arginine-beta-naphthylamide (PAbetaN) of resistant isolates with no mutations in rpoB and different RIF MICs reduced the MIC by >10-fold and restored the synergism between RIF and COL in time-kill studies, whilst it had no effect on strains carrying rpoB mutations. In conclusion, the emergence of elevated RIF MICs in A. baumannii isolates from our geographical area was mostly caused by mutations in rpoB; low to intermediate RIF MICs were also caused by altered membrane permeability to the drug. The phenomenon was contributed by the selection of two prevalent clones both assigned to ST2 genotype. These data may have implications for the correct identification of cases with A. baumannii infection that would not benefit from addition of RIF to COL. PMID- 22055531 TI - Role of caspofungin in restoring the impaired phagocyte-dependent innate immunity towards Candida albicans in chronic haemodialysis patients. AB - Phagocyte-dependent cellular immunity in chronic kidney disease patients undergoing haemodialysis treatment is frequently impaired owing to the uraemic state, resulting in an intrinsic susceptibility to developing invasive fungal infections with high mortality rates. Since synergism between phagocytic cells and antifungal drugs may be crucial for successful therapy, the aim of this study was to evaluate the effects exerted by caspofungin (CAS) on the functional activities of polymorphonuclear cells (PMNs) in haemodialysed patients (HDs) towards Candida albicans compared with those of PMNs from healthy subjects (HSs). PMNs were separated from venous blood samples of 66 HDs and 30 HSs (as controls), and measurement of phagocytic and intracellular fungicidal activities of HD-PMNs and HS-PMNs was performed in the presence of CAS at the minimum inhibitory concentration (MIC) and at sub-MICs. CAS-free controls were also included. In the drug-free test condition, no significant difference between the phagocytic activity of HD-PMNs and HS-PMNs was detected. In contrast, a progressive decline in the intracellular killing activity of HD-PMNs against proliferating yeasts was observed. CAS at MIC and sub-MIC levels was able to improve significantly the intracellular fungicidal activity of HD-PMNs against C. albicans, restoring their functionality. These findings provide evidence that CAS exerts a synergistic effect on HD-PMNs against C. albicans, being able to strength the depressed intracellular killing activity. These results corroborate the use of CAS as an effective therapeutic option for the treatment of invasive fungal infections in HDs, in whom even a marginal influence of antifungal drugs on host response may have a relevant effect. PMID- 22055532 TI - Molecular diversity in mechanisms of carbapenem resistance in paediatric Enterobacteriaceae. AB - Development of carbapenem resistance in Enterobacteriaceae has impacted Clinical and Laboratory Standards Institute (CLSI) guidelines, infection control approaches and treatment strategies. The clinical, phenotypic and genotypic characteristics of carbapenem-resistant Enterobacteriaceae (CRE) infections at paediatric referral centres are not well described. CRE were identified through the clinical microbiology laboratory at Seattle Children's Hospital (Seattle, WA). Clinical data were retrieved from medical records. Resistance testing, polymerase chain reaction (PCR) for resistance determinants, and Escherichia coli transformation were carried out for each isolate. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were used to characterise strain relatedness. PCR amplification and sequencing as well as sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) were used to investigate porin alterations. Six CRE isolates were identified between 2002 and 2010. Significant molecular diversity was documented in their mechanisms of resistance, including plasmid-mediated serine carbapenemase (KPC) and metallo-beta-lactamase (IMP), chromosomally encoded beta-lactamase (SME) and porin alterations with extended-spectrum beta-lactamases. Patients had underlying health conditions and were from geographically diverse regions. In one case, PFGE of serial isolates documented the development of resistance in a previously susceptible strain. Molecular investigation of this strain identified insertion of the genetic mobile element insertion sequence ISEcp1 in the ompK36 gene, conferring a functional porin alteration as demonstrated by SDS-PAGE. This is the first description of porin disruption by ISEcp1 in a CTX-M-15-positive isolate. This is the largest report of paediatric CRE to date. This diverse description of demographic, phenotypic and molecular characteristics highlights the challenge of CRE infections in high-risk paediatric patients and that attention to emerging resistance mechanisms (including membrane alteration) at paediatric referral centres is essential. PMID- 22055533 TI - A factorial analysis of water-binding properties and firmness of heated, comminuted pork liver and pork loin products as influenced by addition of sodium chloride and pH regulators. AB - Canned, pasteurized, comminuted pork liver and pork loin were used for a factorial study to evaluate the effects of the addition of sodium chloride (0 and 1.8%), acid and alkaline mono- and diphosphates (0 and 0.3% P(2)O(5)), acetic acid (0 and 0.25%), sodium acetate (0 and 0.63%) and glucono-delta-lactone (0 and 0.5%) on their water-binding properties and firmness. The water-binding properties were evaluated by measuring cooking losses (for both types of product) and by moisture release by centrifugation (for the liver products only). The liver products had much better water-binding abilities and were softer than the loin products. The interaction of salt and pH regulators also differed greatly from the interaction for the comminuted loins, resulting in a barely perceptible effect of the pH regulating compounds on the water-binding abilities of the salt containing comminuted liver. The firmness of the salt-containing liver products was greatly reduced by the addition of acidulants. The loin products were normally affected by the compounds tested, with the exception of Na(4)P(2)O(7). The added amount of this diphosphate caused a considerable rise in the product pH, which resulted in a large reduction in cooking loss, thus leaving no possibility of an extra reduction by the combination of salt and Na(4)P(2)O(7). PMID- 22055534 TI - Generalization of a method for the characterization of quick frozen beef. AB - The lack of standardized tests for determining if a product can be defined as 'quick frozen' is a source of difficulty in the commercialization of foods. An even greater difficulty is the fact that there is no one definition of a quick frozen food. With the aim of partially filling this gap, a previous paper developed a simple physical method of characterizing quick frozen beef. The study was carried out with meat cuts cooled by means of heat transfer perpendicular, in a sense, to the meat fibres with 'quick frozen' being defined by a minimum average freezing rate. In the present paper the characterization method is generalized for either heat transfer perpendicular with, or parallel to, beef fibres, 'quick frozen' being defined either by a maximum freezing time or a minimum freezing rate. PMID- 22055535 TI - Effects of temperature and storage duration on the microflora, physicochemical and sensory changes of vacuum- or nitrogen-packed pork. AB - A comparative study of vacuum packaging alone or vacuum followed by nitrogen back flushing of fresh pork stored at -4, 0, 3 and 7 degrees C for 49 days showed that pork stored at -4 degrees C generally exhibited small changes in microbial numbers, pH, exudate, appearance and off-odour. Samples stored above 0 degrees C could not be kept beyond 14-28 days without obvious changes, regardless of package atmospheres. Storage life was inversely related to temperature. The initial psychrotrophs consisted primarily of Pseudomonas spp. but these organisms diminished as Lactobacillus spp. multiplied in both atmospheres. Few significant differences in numbers of fecal coliforms were found between treatments, although the numbers tended to increase in samples stored at 7 degrees C. Nitrogen packaging did not reduce exudate losses as compared with vacuum packaging. PMID- 22055536 TI - Cutability comparisons of Charolais crossbred bulls and steers. AB - Seventy-two sides (eighteen sides from each sex-breed group) from carcasses of half-blood or three-quarters-to-seven-eighths-blood Charolais bulls or steers of known history and age, handled alike from weaning to slaughter, were used. All cattle were fed in a commercial feedlot (average days-on-feed was 186) and slaughtered in a commercial packing plant. Comparisons were made for percentages of (1) untrimmed wholesale cuts, (2) partially boneless subprimals (trimmed of fat in excess of 1.9 cm), (3) partially boneless retail-ready cuts (trimmed of fat in excess of 0.95 cm) and (4) boneless retail-ready cuts (trimmed of fat in excess of 0.95 cm). Bulls had higher percentages than steers of chuck and round at all stages of trim. Steers had higher percentages of untrimmed, wholesale loin and partially boneless shortloin (1.9 cm fat) than bulls but steer percentages of shortloin cuts trimmed to 0.95 cm of fat did not differ from those of bulls. Bulls averaged 48.05%, while steers averaged 45.45%, major boneless, closely trimmed retail-ready cuts. After the lean trim was adjusted to 25% chemical fat, bulls had 27.70% lean trim and 5.65% fat trim while steers had 24.30% lean trim and 12.15% fat trim. No difference in the percentage of retail-ready cuts was attributable to breed; however, the three-quarters-to-seven-eighths-blood Charolais group had a lower percentage of standardized fat trim and a slightly higher percentage of bone than the half-blood group. PMID- 22055537 TI - The 'cultural inflation of morbidity' during the English mortality decline: a new look. AB - This article contributes to the debate about using insurance records to reconstruct historical experiences of sickness during the Western mortality transition. Critics regard these sources as problematic as they measure morbidity indirectly through absences from work; these might be determined not by timeless biological criteria but by more contingent factors, notably shifting norms surrounding the sick role and responses to economic incentives (for which we adopt the generic term 'cultural inflation of morbidity'). We review historical demographers' contributions to this literature and discuss the concepts of moral hazard and the principal/agent problem as developed by health economists. This leads us to frame three empirical tests for 'cultural inflation' which allow us to assess the validity of insurance records for deriving morbidity trends: was there an increasing frequency of claims for complaints of diminishing severity; were unduly prolonged claims noticeable, particularly by older people for whom sickness benefit may have compensated for income insecurity; and did the insurer satisfactorily manage the agency problem to ensure reliable physician gatekeeping? We analyse records of the Hampshire Friendly Society, an exceptionally well-documented fund operational in Southern England, 1825-1989. Findings are based on a dataset of individual sickness histories of a sample of 5552 men and on qualitative documentary analysis of administrative records. On each count our results fail to demonstrate a cultural inflation of morbidity, except perhaps for those aged over 65. However, occasional discussion in the administrative records of economic incentives encouraging unnecessary prolongation of claims means we cannot rule it out entirely. PMID- 22055538 TI - Is blood thicker than water? Peer effects in stent utilization among Floridian cardiologists. AB - Variations in physician practice are pervasive and costly, and may be harmful. The objective of much policy in the West is to increase the interconnectedness of physicians, furthering the transfer of information and thus reducing variation. This study tests whether physicians are influenced by the practice of peers, or if propensity, mere context or sorting of like-minded physicians better explain similarities and differences in practice. We study US cardiologists who place coronary stents into patients with blocked arteries around the heart. Organized in locally competing physician groups and also as solo practitioners, they see patients in offices, but insert the stents at a shared production facility - the cath lab. We examine their use of the popular drug-eluting coronary stents between their launch and rapid adoption in early 2003, and through the period of late 2006 in which private and public reports of serious late side-effects eventually led to reductions in use. Our analyses use administrative claims data on nearly 1000 cardiologists and their patients in Florida, USA, merged with Florida physician licensure data. Collectively these physicians used these stents nearly a quarter of a million times in the 4 year period reviewed. Pooled and panel linear regressions for device utilization by a physicians are estimated using measures of peer utilization, physician characteristics and controls for unobservable physician characteristics, common shocks and selection effects. We find strong evidence for intra-group but against inter-group practice spillovers. Even when sharing the same lab, competing cardiologists did not appear to correlate practices. Our results are consistent with a view that policies aimed at increasing the interconnectedness of physicians must first consider the organizational barriers and competitive forces that can stymie knowledge transfer even among physicians working closely together. PMID- 22055539 TI - Cardiopulmonary complications after primary shoulder arthroplasty: a cohort study. AB - OBJECTIVE: To study the frequency and predictors of 90-day cardiopulmonary complications following primary shoulder arthroplasty. METHODS: We used prospectively collected data from the Mayo Clinic Total Joint registry from 1976 to 2008. We used univariate and multivariable-adjusted Cox regression analyses to examine the association of age, gender, body mass index, comorbidity assessed by Deyo-Charlson index, American Society of Anesthesiologist class, implant fixation (cemented versus not), and underlying diagnosis with the risk of 90-day cardiopulmonary complications after primary shoulder arthroplasty. Odds ratio (OR) with 95% confidence interval (CI) and P values are presented. RESULTS: A total of 3480 patients underwent 4019 primary shoulder arthroplasties. Ninety-day cardiac and thromboembolic complication rates following primary shoulder arthroplasty were 2.6% (92/3480) and 1.2% (42/3480). After multivariable adjustment, age >70 years (OR, 2.7; 95% CI: 1.2-5.9; P value = 0.01; relative to age <60), Deyo-Charlson comorbidity index of 1 or more (OR, 3.27; 95% CI:1.9-5.6; P < 0.0001; relative to index of 0), and prior cardiac events (OR, 7.87; 95% CI: 4.89-12.68; P < 0.0001; relative to no prior event) were associated with higher odds of 90-day cardiac complications. Due to a few thromboembolic events, only univariate analyses were performed. Univariately, female gender, age >70 years, body mass index 25 to 29.9 kg/m(2), Deyo Charlson index of 1 or more, underlying diagnosis of trauma, prior thromboembolic event, and surgery type were each associated with significantly higher risk of 90-day thromboembolic event (P <= 0.03 for all). CONCLUSIONS: Cardiac and thromboembolic complications are uncommon after primary shoulder arthroplasty. Patients can be informed of their risk of cardiac complications following shoulder arthroplasty based on the presence of risk factors. PMID- 22055540 TI - Ultrasound-defined remission and active disease in rheumatoid arthritis: association with clinical and serologic parameters. AB - OBJECTIVE: To assess the association of clinical and/or serological parameters with ultrasound-defined disease activity in rheumatoid arthritis (RA). METHODS: Retrospective analysis of 149 consecutive RA patients routinely assessed by sonography of the wrists, metacarpo-phalangeal, and proximal interphalangeal joints. Semiquantitative scoring of synovial hypertrophy/effusion and power Doppler (PD) signals was performed. Sonographic remission was defined by the absence of PD signals. Number of tender and swollen joints, global assessment of disease activity by the physician (VAS-phys) and patient (VAS-pt), C-reactive protein (CRP), erythrocyte sedimentation rate, duration of morning stiffness (MS), simplified disease activity index, disease activity score for 28 joints, clinical disease activity index, and health assessment questionnaires were recorded. RESULTS: PD signals as a sign of active disease were observed in 117 (78.5%) RA patients. CRP, erythrocyte sedimentation rate, and MS were higher in patients with PD signals than in patients in remission. CRP >5.0 mg/L (normal values 0-5.0 mg/L), MS >15 minutes, or the combination of both revealed odds ratios of 5.0, 3.0, or 18.9, respectively, to indicate sonography-defined active disease. The other parameters showed no association with the presence or absence of PD-signals. CONCLUSIONS: Sonography-defined disease activity is associated with CRP and MS, whereas current composite scores and its clinical components did not match this definition. PMID- 22055541 TI - Examining how antiphospholipid antibodies activate intracellular signaling pathways: a systematic review. AB - OBJECTIVES: Diverse experimental evidence exists implicating the activation of various different cell surface receptors and intracellular pathways by antiphospholipid antibodies (aPL). This evidence has been generated using a number of different cell types with varying numbers of aPL from different sources and disease subtypes. This experimental variability complicates the comparison of results from different studies. We therefore undertook a systematic review of the literature to provide a critical analysis of the strength of the evidence that specific receptors and signaling pathways are important in the pathogenesis of antiphospholipid syndrome. METHODS: We searched PubMed and EMBASE for studies in which the effects of aPL on cell surface receptors or intracellular signaling pathways were measured in vitro or in vivo. Each publication was systematically examined to note the following points: antibody type and source, outcome measures, use of receptor/signaling pathway inhibitors, and cell type and origin. RESULTS: We identified 10 original studies on toll-like receptors (TLR), 14 on protein kinases, and 13 on nuclear factor kappa B (NFkappaB). There was considerable heterogeneity between studies. Nevertheless, convincing evidence from multiple approaches implicates TLR4, p38 mitogen-activated protein kinase (MAPK), and NFkappaB in mediating pathogenic effects of antiphospholipid antibodies. CONCLUSIONS: TLR4, p38 MAPK and NFkappaB are involved in mediating pathogenic effects of aPL on different cell types and may be potential therapeutic targets in antiphospholipid syndrome. PMID- 22055542 TI - Hand tendon involvement in rheumatoid arthritis: an ultrasound study. AB - OBJECTIVE: To assess the prevalence and the distribution of tendon involvement in the hands and wrists of patients with rheumatoid arthritis (RA) describing in detail the ultrasound (US) morphostructural and vascular tendon abnormalities. METHODS: Ninety consecutive RA patients were included in the study. The following tendons were scanned bilaterally: flexor pollicis longus tendon, flexor digitorum superficialis, and profundus tendons of the II to the V fingers (at both finger and carpal tunnel levels), flexor carpi radialis tendon, and extensor tendons of the 6 compartments on the dorsal aspect of the wrist. The presence of US findings indicative of tenosynovitis and tendon damage was investigated. RESULTS: Tenosynovitis was found in at least 1 anatomic site of 44 (48.8%) of 90 patients. Tendon damage was found in at least 1 anatomic site of 39 (43.3%) of 90 patients. The focal tendon echotexture derangement was found in 294 of 5400 (5.4%) tendons, the partial and complete tears in 14 (0.3%), and in 3 (0.06%) tendons, respectively. The most frequently involved tendons were the flexor tendons of the II, III, and IV fingers and the extensor carpi ulnaris tendon. CONCLUSIONS: The present study provides evidence in favor of the ability of US to reveal a relatively high frequency of tendon involvement at the hand and wrist level in RA patients. These data can both facilitate US examinations in daily clinical practice and direct further investigations in the US assessment of tendon involvement in RA. PMID- 22055543 TI - Development of a chemical strategy to produce rare aldohexoses from ketohexoses using 2-aminopyridine. AB - Rare sugars are monosaccharides that are found in relatively low abundance in nature. Herein, we describe a strategy for producing rare aldohexoses from ketohexoses using the classical Lobry de Bruyn-Alberda van Ekenstein transformation. Upon Schiff-base formation of keto sugars, a fluorescence labeling reagent, 2-aminopyridine (2-AP), was used. While acting as a base catalyst, 2-AP efficiently promoted the ketose-to-aldose transformation, and acting as a Schiff-base reagent, it effectively froze the ketose-aldose equilibrium. We could also separate a mixture of Sor, Gul, and Ido in their Schiff-base forms using a normal-phase HPLC separation system. Although Gul and Ido represent the most unstable aldohexoses, our method provides a practical way to rapidly obtain these rare aldohexoses as needed. PMID- 22055544 TI - [Effectiveness assessment in public health: the strength of "weak evaluation designs"]. PMID- 22055545 TI - [Effectiveness assessment in public health: conceptual and methodological foundations]. AB - In the last few years, interest has markedly increased in evaluating health programs, especially their social utility and economic efficiency. However, consensus on key issues in evaluation, such as terminology, goals and methods is still a long way off. In this context, we review the main definitions and classifications of evaluation applied to public health programs and policies. We describe the main evaluation designs and their components, focusing on outcome evaluation. Threats to the internal validity of the results of weak evaluation designs are also discussed. The characteristics of public health interventions that limit evaluation with traditional designs are also analyzed. These limitations include the complexity of interventions, usually with multiple components, and the difficulty of forming an equivalent control group with no intervention, especially through random assignment. Finally, a two-step approach to evaluation through weak designs, which takes into account adequacy and plausibility, is described. Adequacy consists of the observation of a change in the selected indicators after the intervention, and would be sufficient to take decisions under certain conditions; at other times, plausibility would need to be analyzed, defined as attribution of the results to the program or intervention. PMID- 22055546 TI - [Evaluative designs in public health: methodological considerations]. AB - Evaluation of public health interventions poses numerous methodological challenges. Randomization of individuals is not always feasible and interventions are usually composed of multiple factors. To face these challenges, certain elements, such as the selection of the most appropriate design and the use of a statistical analysis that includes potential confounders, are essential. The objective of this article was to describe the most frequently used designs in the evaluation of public health interventions (policies, programs or campaigns). The characteristics, strengths and weaknesses of each of these evaluative designs are described. Additionally, a brief explanation of the most commonly used statistical analysis in each of these designs is provided. PMID- 22055547 TI - [Evaluation of health policies and plans]. AB - Evaluation of plans and policies is a key element in their administration and must be performed under real conditions. Such evaluation is complex, as plans and policies include a diverse set of components that operate simultaneously. Moreover, external factors frequently influence those same issues that programs attempt to change. Unless plans and policies are evaluated under real conditions, a policy that effectively reduces the effects of a problem may be deemed ineffective (if the problem increases due to the influence of factors the program does not attempt to affect), or a policy that is unable to influence the problem it attempts to solve may be judged useful (if the magnitude of the problem is being reduced through the influence of factors other than the policy). The present article discusses evaluation of health policies, plans or complex programs, with emphasis on effectiveness assessment, using data from real examples. Among other issues, the need to identify the distinct components of policies and plans is reviewed. This article also describes how to evaluate the outcome or results of a program with indicators from other sources. Aspects related to the timing of evaluation and assessment indicators are analyzed. We discuss situations in which the launch of a new policy or intervention is followed by an increase in the reported magnitude of the problem it attempts to solve. These situations are illustrated by cases in which this increase is attributable to improved detection and by others in which the increase is related to factors external to the intervention. The frequent confusion of the effects of the intervention with other events is covered, with data from some examples. Finally, evaluation of plans that include a wide range of objectives is also addressed. PMID- 22055548 TI - [Economic evaluation of public health interventions]. AB - The scarcity of resources available to meet the growing demand for healthcare services has increased interest in economic evaluation as a tool to inform resource allocation. The aim of economic evaluation is to compare various alternatives for action, in terms of their costs and effects on health, by using several techniques: cost minimization analysis, cost-effectiveness analysis, cost utility analysis, and cost-benefit analysis. Irrespective of the methodology used, any assessment must include scope of the problem, selection of alternatives for comparison, explication of the perspective of analysis and the time horizon, measurement and evaluation of costs and health effects, presentation of results, and sensitivity analysis. In Spain, evaluation of currently ongoing preventive interventions, and adherence to the existing economic evaluation guidelines by researchers would be desirable. PMID- 22055549 TI - [Process evaluation in relation to effectiveness assessment: experiences with school-based programs]. AB - Evaluation of public health interventions usually focus on the quality of design and research methods, and less on the quality of the intervention or process evaluation. In process evaluation of school-based interventions, key issues are how completely the intervention is carried out and adherence to the protocol. In addition, exploration of intermediate variables, such as those that influence (and often predict) preventable behavior, is highly useful. This article describes the basic concepts in this topic, using examples of the effectiveness of some preventive interventions carried out in schools. The interventions discussed were mainly quasi-experimental studies, based on data from programs promoted by public health teams in the city of Barcelona. Data from process evaluation of preventive programs in secondary schools that underwent formal assessment of their effectiveness is provided. The examples are drawn from preventive programs of HIV infection or unprotected sexual intercourse (PRESSEC program) and drug consumption prevention (the PASE, PASE.bcn and x kpts programs). These examples show why the intervention process influences the impact of the programs and their results. Thorough planning of process evaluation is essential to obtain valid indicators that will identify, in the effectiveness evaluation of the intervention, the most efficacious strategies to obtain positive outcomes. PMID- 22055550 TI - [Health technology assessment in public health interventions: is prevention better than cure?]. AB - Medical activities are increasingly performed with preventive purposes, as part of community programs for secondary prevention but also as part of many clinical activities. However, there are few evaluations of preventive and health promotion activities and, in general, these evaluations only assess aspects of efficacy/effectiveness with little consideration of cost and cost-effectiveness and even less of the ethical, legal, social or organizational consequences. Given the growing interest in evaluation of these interventions from different perspectives, health technology assessment (HTA) has emerged as a multidisciplinary analysis strategy with distinct methodological approaches that may be useful to health administrations and policy-makers for decision making at different levels (micro, meso and macro). This manuscript discusses the characteristics and differential aspects related to assessment of preventive and health promotion activities. This type of evaluation poses constraints, limitations and challenges that should be considered during the process of HTA. In the case of public health there are additional challenges, because the evidence must satisfy a diverse audience, including public health professionals, clinicians, politicians, managers, economists and consumers. The challenge is even greater when evaluating complex, integrated community interventions in which local and contextual aspects are of tremendous importance. In addition, assessment of ethical issues is of the utmost importance since these issues comprise the origin of health services and the target populations are usually healthy. PMID- 22055551 TI - [Assessing the effectiveness of vaccination programs]. AB - Vaccines have contributed enormously to reducing the incidence of many communicable diseases. The protective efficacy of a vaccine refers to the health effects of the vaccine applied in optimal, ideal conditions, whereas the effectiveness of a vaccination program refers to the health effects of vaccination in the vaccinated individuals in clinical practice or within public health programs, which may differ widely from optimal conditions. Vaccine efficacy is estimated by randomized clinical trials. In contrast, effectiveness can be measured by various types of epidemiological studies: randomized community trials, in which the target vaccine is randomly assigned to a group and disease incidence in this group is compared with that of an unvaccinated group; cohort studies, which are observational epidemiological studies in which the vaccination status is known in healthy vaccinated (vaccinated cohort) and unvaccinated (unvaccinated cohort) people and the occurrence of the disease in the two groups is studied; and observational case-control studies, in which two groups are selected; one with the disease under investigation (cases) and the other without (controls), and vaccination histories are investigated in the two groups. Vaccine effectiveness may also be estimated by comparing attack rates in epidemic outbreaks or secondary attack rates in the home, or by screening. PMID- 22055552 TI - How does topical lidocaine relieve pain? PMID- 22055553 TI - Estimate at your peril: imputation methods for patient withdrawal can bias efficacy outcomes in chronic pain trials using responder analyses. PMID- 22055554 TI - Long-distance walking effects on trans-tibial amputees compensatory gait patterns and implications on prosthetic designs and training. AB - Trans-tibial amputees are advised to walk as much as able people to achieve healthy and independent life. However, they usually have difficulties in doing so. Previous researches only included data from a few steps when studying the gait of amputees. Walking over a long distance was rarely examined. The objective of this study was to investigate the changes in spatial-temporal, kinetic and kinematic gait parameters of trans-tibial amputees after long-distance walking. Six male unilateral trans-tibial amputees performed two sessions of 30-min walking on a level treadmill at their self-selected comfortable speed. Gait analysis was undertaken over-ground: (1) before walking, (2) after the 1st walking session and (3) after the 2nd walking session. After the long-distance walking, changes in spatial-temporal gait parameters were small and insignificant. However, the sound side ankle rocker progression and push-off were significantly reduced. This was due to the fatigue of the sound side plantar flexors and was compensated by the greater effort in the prosthetic side. The prosthetic side knee joint showed significantly increased flexion and moment during loading response to facilitate the anterior rotation of the prosthetic shank. The prosthetic side hip extensors also provided more power at terminal stance to facilitate propulsion. Endurance training of the sound side plantar flexors, and improvements in the prosthetic design to assist anterior rotation of the prosthetic shank should improve long-distance walking in trans-tibial amputees. PMID- 22055555 TI - Ionoluminescence studies of natural kyanite mineral from different parts of Indian origin. AB - Ionoluminescence (IL) studies of two natural kyanite (Al(2)SiO(5)) minerals collected from different regions of India was carried out using 120 MeV Ag(9+) ions in the fluence range of 1.50-10.5 * 10(11)ions/cm(2). Identical emission peaks were observed in both the samples at ~416, 463, 530-540 nm along with other emission peaks at ~689 nm, 706 nm (sharp) and 770 nm (broad). The sharp emission peaks at 689 nm correspond to R lines of Cr(3+) impurities and are related to transition of (2)E(g)->(4)A(2g). The sharp and broad emission peaks in the range of 706-770 nm are attributed to Fe(3+) impurities and are related to the transition of (4)T(1g)->(6)A(1g). The peak in the range of 530-540 nm is attributed to Mn(2+) impurities and is related to the transition of (4)T(1) >(6)A(1). IL peak intensity decreases with the Ag(9+) ion fluence which might be due to the thermal quenching/amorphization, caused by the ion beam irradiation. The amorphization in the sample was explained with the help of thermal spike model (TSM). These results demonstrated that IL is a very sensitive technique for impurity characterization and differentiating the origin of minerals. PMID- 22055556 TI - A comparative DFT study of the structure and vibration spectra of the intermediate of the OCS heterogeneous reaction. AB - Density functional theory (DFT) calculations using the different functional of PBE1PBE, PBEPBE, LSDA, B3LYP, MPW1PW91, B3P86 and B3PW91 have been carried out to study the adsorption of HCO(3)(-) species on the Al(2)O(3) catalyst. The geometrical structures and vibration spectra were obtained using DFT and compared with the corresponding experimental values. Theoretical calculations show that the calculated IR spectra for PBE1PBE and MPW1PW91 method are in good agreement with the experimental spectroscopic results. PMID- 22055557 TI - A thymidine-terminated molecular beacon for selective Hg2+ or sequence-specific DNA assay. AB - A new molecular beacon (MB) in which fluorescein (FAM) attached to its 3' end acts as a fluorophore and a bridged thymidine-Hg-thymidine (T-Hg-T) complex acts as a quencher is designed. The fluorescence resonance energy transfer (FRET) between the fluorophore and the quencher results in annihilation of the FAM fluorescence. Experimental conditions that govern the fluorescence quenching, such as number of thymidine bases, pH value, and salt concentration, have been optimized. The MB was found to be highly selective for Hg(2+) among a number of metal ions investigated. In the presence of single-stranded (ss-) target oligonucleotides (ODNs) with bases complementary to those in the loop of MB, the FAM fluorescence can be largely restored due to DNA duplex formation. The present method for DNA assay is also sequence-specific and can determine target ODN concentration at a nanomolar level. The substitution of the quencher group in a conventional MB molecule with simple thymidine bases affords an inexpensive ODN that retains the unique property of the MB molecule. PMID- 22055558 TI - Bovine muscle shortening and protein degradation after electrical stimulation, excision and chilling. AB - Electrical stimulation-dependent improvement in beef tenderness resulted from mechanisms other than avoidance of cold shortening in excised muscle chilled at a normal rate (10 degrees C at 10h post-stimulation). At normal chilling rate, electrical stimulation enhanced degradation of the myofibrillar proteins, alpha actinin and troponin-T, and increased the amount of a 30 000 dalton protein, as assessed by gel electrophoresis, whereas sarcomere lengths were not different from unstimulated muscle. Under slightly accelerated chilling conditions (10 degrees C at 5 h post stimulation), electrical stimulation prevented cold shortening but the meat was more tender than, and had the same sarcomere length as, unstimulated muscle chilled to 10 degrees C in 10 h. Electrical stimulation did not improve the tenderness of beef chilled at a rapid rate (10 degrees C at 2 h post stimulation), nor did it prevent cold shortening when muscles were chilled rapidly. PMID- 22055559 TI - The influence of exhaustion and electrical stimulation on the meat quality of young bulls: Part 1-Post-mortem pH and temperature. AB - After designing a method of handling cattle so that they reproducibly developed DFD meat, pH and temperature in cattle developing DFD and normal meat, respectively were studied. The influence of low voltage stimulation on both groups was also investigated. Depending on final pH and other characteristics of the meat, the carcasses could be assigned to subgroups representing pronounced DFD, slight DFD and normal meat, with and without electrical stimulation. In normal and in pronounced DFD carcasses electrical stimulation speeded up the pH drop but did not affect the final state of the meat. In stressed animals the pH values are variable for the first few hours post mortem. This effect is enhanced by electrical stimulation which, in carcasses with slight DFD (from stressed but not exhausted animals), may produce extremely fast pH drop and PSE-like meat. There is no evidence that electrical stimulation would influence the incidence of DFD in cattle slaughtered under commercial conditions. In normal animals electrical stimulation raised the carcass temperature during the first few hours post mortem by approximately 2 degrees C. Carcasses from stressed animals had a higher temperature, independent of stimulation. PMID- 22055560 TI - The influence of exhaustion and electrical stimulation on the meat quality of young bulls: Part 2-Physical and sensory properties. AB - The physical and sensory properties of meat from sixteen exhausted and sixteen gently treated young bulls were investigated. The influence of electrical stimulation was also studied. The meat was divided into three groups-meat with ultimate pH <= 5.80 (normal meat), 5.81-6.19 (medium meat) and >=6.20 (DFD meat), respectively. DFD meat showed typical DFD properties and had a higher initial tenderness but a smaller increase in tenderness than normal meat during storage. The medium meat was tough and behaved in some ways as DFD meat and in others like normal meat. Lower correlation between shear force measurement and sensory evaluated tenderness was obtained for DFD than for normal meat. The cooking loss of DFD meat was about 10% lower than that of normal and medium meat. No significant correlation could be found between storage loss, cooking loss, frying loss and juiciness. The electrically stimulated meat was-especially for normal meat-more tender and juicy than unstimulated meat. No obvious influence due to electrical stimulation was noticed on colour, cooking loss, frying loss or storage loss. Electrical stimulation of stressed, but not exhausted, animals may produce meat with PSE properties. PMID- 22055562 TI - Erratum. PMID- 22055561 TI - The influence of temperature on shortening and rigor onset in beef muscle. AB - At sufficient ATP concentration and temperatures below about 15 degrees C, pre rigor beef muscles (neck muscles) contract; this phenomenon is known as cold shortening. There is also a contracture at higher temperatures occurring just before rigor onset which is called rigor shortening. While rigor shortening starts in neck muscles at pH around 6.3-6.0 and at about 2 MUMol ATP/g muscle, cold shortening can begin at pH around 7.0 and the full ATP concentration (4 MUMol ATP/g) in the muscle. Shortening can take place as long as there is no irreversible formation of the actomyosin complex in the muscle, i.e. before rigor onset occurs, which can be measured by intermittent loading of the muscle. The degree of extensibility which follows starts to decrease at the moment of rigor onset. This irreversible loss of extensibility at temperatures between the freezing point (-1 degrees C) and physiological temperatures (38 degrees C) starts at various pH values and ATP concentrations in the muscle. At 38 degrees C the rigor onset occurs at pH 6.25 and about 2 MUMol ATP/g muscle, dropping at 15 degrees C to pH 5.75 and 1 MUMol ATP/g muscle. At 0 degrees C, as at all temperatures below 10 degrees C, the loss of extensibility at medium loads (about 250 g/cm(2)) begins shortly after cold shortening. This loss of extensibility is reversible by increasing the load or raising the temperature. The irreversible loss, or rigor onset, however, occurs at 0 degrees C with pH of 6.1-6.2 and 1.8 2.0 MUMol ATP/g muscle. Thus, the onset of rigor is influenced by more than one factor. Temperature, pH and ATP concentration each play a role. Maximum loss of extensibility or completion of rigor is reached between 10 degrees C and 38 degrees C at pH 5.5-5.6 and less than 0.5 MUMol ATP/g muscle. At 0 degrees C the completion of rigor takes place at pH 6.0, but still at 0.5 MUMol ATP/g muscle. The latter fact shows that the completion of rigor is solely dependent on the ATP concentration in the muscle; nevertheless, the pH of rigor completion is higher in the extreme cold shortening range. This is apparently due to a different pH/ATP relationship in muscles at low temperatures. The results are discussed in terms of changes in the concentration of Ca(2+) ions and ATP. The results are of particular interest for the handling of hot-boned meat; that is, for both the cooling of pre-rigor muscle and the use of hot-boned meat for processing. PMID- 22055563 TI - Effects of altered carcass suspension during rigor mortis on tenderness of pork loin. AB - A total of 32 porcine carcasses from Danish Landrace and Yorkshire breeds, slaughtered at approximately 90 kg live weight, were utilised in two experiments (replicates) to evaluate the effect of altered carcass suspension on Warner Bratzler (WB) shear force, sarcomere length, myofibrillar fragmentation and cooking loss in the longissimus dorsi (LD). Carcasses used in the experiments all showed pH(1) values above 6.0 and ultimate pH below 5.8. From each replicate, the two sides of 16 carcasses were suspended by one of two methods: conventional suspension from the Achilles tendon or pelvic suspension from the obturator foramen. WB values were measured at three locations taken from the posterior section of the LD muscle. Pelvic suspension decreased WB values (p < 0.001) and increased sarcomere lengths (p < 0.001) whereas cooking loss was unaffected by method of suspension. The significant interactions between suspension and replicate (p < 0.01) and between suspension and sample location (p < 0.001) revealed that the tenderising effect of pelvic suspension increased with increasing WB level in the conventional suspended carcass sides. Myofibril fragmentation showed inconsistent response to suspension method. PMID- 22055564 TI - A comparison of alternative methods for predicting the carcass composition of crossbred lambs of different breeds and crosses. AB - Carcass data for a total of 2808 lambs from three breed trials were used to evaluate a series of linear measurements, visual scores and the proportions of tissues in joints as predictors of carcass composition. The trials involved crossbred lambs out of different dam types by sires of the main British meat breeds and by Ile de France, Oldenburg and Texel sires. Each trial was carried out over a number of years and involved approximately equal numbers of female and castrated male lambs. Potential predictors were examined in terms of the precision of prediction and in terms of the robustness of prediction equations to differences in sire breed and sex. The overall standard deviation (s.d.) of carcass lean percentage averaged over trials was 4.3. Combinations of simple measurements, including visual fat scores, percentage perinephric and retroperitoneal fat in carcass and M. longissimus dimensions achieved a residual s.d. of 2.5 for carcass lean percentage. The application of an overall prediction equation to individual sire breed means resulted in considerable bias (predicted actual lean percentage): the mean square deviation was 0.75. In comparison, the sex differences were relatively unimportant. The precision of sample joints was examined in relation to their cost of dissection. The best end neck and shoulder joints offered a high level in relation to cost: typical residual s.d. were 1.5 for carcass lean percentage. Joints and combination of joints with high predictive precision tended to have equations that were robust to differences between sire breeds. PMID- 22055565 TI - Hot cutting of goat carcasses following early post-mortem high temperature ageing. AB - Hot cutting of goat sides into bone-in joints, such as leg, shoulder and loin, 3 h after the sides were left hanging at an ambient temperature of 34 degrees C with (treatment II) or without (treatment I) subsequent chilling prior to freezing did not adversely affect colour of meat, tenderness, cooking loss or water-holding capacity compared with normal chilling. The latter process (treatment III) significantly (P < 0.05) increased evaporative weight loss from the sides. Differences in colour, shear force, evaporative weight loss, cooking loss, drip loss from the leg joint and water-holding capacity between treatment I, where sides were hung at room temperature for 3h, and treatment II, where sides were given an additional chilling period of 21h after hanging, were not significant. These findings indicate that, in countries with ambient temperatures above 30 degrees C, goat sides or carcasses can be cut hot after a 3h hanging period at ambient temperature and subsequently frozen without deterioration in the quality or processing properties of the meat. PMID- 22055566 TI - Determination of pH in meat. AB - The pH of 80 beef and 120 pork muscles was determined electrometrically using different electrode systems and different presentations of samples; that is, directly from the muscle, from a meat-water mixture and from a meat homogenate. The results showed statistically significant differences (p < 0.001). Differences between electrodes appear to be greater than the differences due to the different presentations of the meat samples. Certain methods gave systematically lower or higher pH values than others. On the other hand, these differences were not very large and the repeatability of each method was low. On the basis of the results, however, no pH measurement method could be considered better than the others. Further harmonization of the methods used for pH measurement of meat is still needed. PMID- 22055567 TI - Carbon-13 and proton NMR studies of post-mortem metabolism in bovine muscles. AB - Proton and carbon-13 NMR was used to investigate post-mortem metabolism in bovine muscles at 26 degrees C during the first 10h after slaughter. WALTZ-16 decoupling was used to eliminate the proton couplings in the (13)C spectra and the 'jump and return' pulse sequence was used to suppress the water resonance in the (1)H-NMR experiments. With carbon-13 NMR the glycogen breakdown and the lactate development could be followed. This was compared with the lactate, creatine and phosphocreatine development as measured by proton NMR. The intracellular pH was estimated from the chemical shift of the abundant dipeptide, carnosine, as measured in the (1)H- and (13)C-NMR spectra. These were compared with similar measurements obtained earlier using phosphorus-31 NMR. The three independently determined pH profiles were in excellent agreement with one another, as well as with results obtained with the standard iodoacetate extraction method. In the course of these studies we observed that the post-mortem metabolism in cow and heifer was slow and that it took four more hours to complete compared to bull or young bull. After 10 h the pH was 5.9 in bull and 6.1 in cow. Phosphocreatine had completely disappeared after 3.5 h in bull samples while the lactate continued to increase even after 10h. The curves obtained by carbon-13 and proton NMR for the increase in lactate during the first 10 h post mortem were very similar. Moreover, plots for the increase in the lactate level versus the intracellular pH decrease showed a linear relationship, indicating that anaerobic glycolytic activity is the main determining cause for the intracellular pH decrease. Various other parameters, such as the ratio of unsatirated to saturated fatty acid side chains and the presence of amino acids and taurine, could be measured from the in vivo carbon-13 NMR spectra. However, no gross changes occured in any of these parameters during the first 10 h post mortem. PMID- 22055568 TI - Zebrafish Mms2 promotes K63-linked polyubiquitination and is involved in p53 mediated DNA-damage response. AB - The ubiquitin-conjugating enzyme Ubc13 together with a Ubc/E2 variant (Uev) form a stable complex and mediate K63-linked polyubiquitination, which is implicated in DNA damage tolerance in yeast and mammalian cells. The zebrafish Danio rerio is a lower vertebrate model organism widely used in the studies of vertebrate development and environmental stress responses. Here we report the identification and functional characterization of two zebrafish UEV genes, Drmms2 and Druev1. Their deduced amino acid sequences indicate that the two UEV genes evolved separately prior to the appearance of vertebrates. Both zebrafish Uevs form a stable complex with DrUbc13 as well as Ubc13s from yeast and human, and are able to promote Ubc13-mediated K63 polyubiquitination in vitro, suggesting that their biochemical activities are conserved. Despite the fact that both zebrafish UEV genes can functionally replace the yeast MMS2 DNA-damage tolerance function, they exhibited differences in DNA-damage response in zebrafish embryos: ablation of DrMms2, but not DrUev1, enhances both spontaneous and DNA-damage induced expression of p53 effectors p21 and mdm2. In addition, DrUbc13 specifically binds Drp53 in an in vitro assay. These observations collectively indicate that zebrafish Mms2 and Ubc13 form a stable complex, which is required for p53 mediated DNA-damage response. PMID- 22055569 TI - Enhanced resistance of yeast mutants deficient in low-affinity iron and zinc transporters to stannous-induced toxicity. AB - Tin or stannous (Sn(2+)) compounds are used as catalysts, stabilizers in plastic industries, wood preservatives, agricultural biocides and nuclear medicine. In order to verify the Sn(2+) up-take and toxicity in yeast cells we utilized a multi-elemental analysis known as particle-induced X-ray emission (PIXE) along with cell survival assays and quantitative real-time PCR. The detection of Sn(2+) by PIXE was possible only in yeast cells in stationary phase of growth (STAT cells) that survive at 25mM Sn(2+) concentration. Yeast cells in exponential phase of growth (LOG cells) tolerate only micro-molar Sn(2+) concentrations that result in intracellular concentration below of the method detection limit. Our PIXE analysis showed that STAT XV185-14c yeast cells demonstrate a significant loss of intracellular elements such as Mg, Zn, S, Fe and an increase in P levels after 1h exposure to SnCl(2). The survival assay showed enhanced tolerance of LOG yeast cells lacking the low-affinity iron and zinc transporters to stannous treatment, suggesting the possible involvement in Sn(2+) uptake. Moreover, our qRT-PCR data showed that Sn(2+) treatment could generate reactive oxygen species as it induces activation of many stress-response genes, including SOD1, YAP1, and APN1. PMID- 22055571 TI - Editorial. PMID- 22055572 TI - Connective tissue differences in the strength of cooked meat across the muscle fibre direction due to test specimen size. AB - Systematic variations in the tensile strenght of cooked beef M. semitendinosus across the muscle fibre direction due to the cross-sectional size of specimens are demonstrated in specimens from (a) longitudinal and (b) transverse slices. The strength perpendicular to the fibre direction of longitudinal slices of thickness 0.25-5.75 mm varied by a factor of 2, thicker slices being stronger. This factor of 2 is in approximate agreement with the difference in strength of transverse versus longitudinal slices across the fibre direction. These variations of strength due to specimen geometry are explained on the basis of the increasing likelihood of including a ribbon of the perimysial connective tissue network which is continuous along the whole length of the test piece in larger samples. The breaking strength of small cross-sectional area specimens is likely to be dominated by the strength of the endomysial-perimysial junction. Larger cross-sectioned specimens, by including continuous strands of the perimysial network, have higher strengths resulting from the necessity to break these strands. These findings highlight the need to specify specimen dimensions in tensile test results. They also show that by manipulating specimen geometry, the relative magnitude of the two mechanisms of connective tissue fracture (endomysial-perimysial separation and perimysial strand fracture) may be assessed. PMID- 22055570 TI - Plasticity in mast cell responses during bacterial infections. AB - Mast cells (MCs) have been implicated in orchestrating the host's early innate immune and adaptive immune responses in several models of acute bacterial infections. Most of this activity results in early clearance of the bacteria and timely resolution of infection. However, during chronic infections because of the prolonged nature of MC-bacterial interactions, the role of the MC in determining the fate of infection is markedly more complex. Depending on the nature of the pathogen, severity of infection, and its association with a preexisting inflammatory disease, MCs may promote rather than contain chronic infections and exacerbate their pathological sequellae. PMID- 22055573 TI - Effect of post-mortem conditioning of ewe carcasses on instrumental texture profile of cooked thigh muscles. AB - The semimembranosus (SM) and semitendinosus (ST) muscles were removed from 18 four to five year old Bannur breed ewes which were slaughtered and carcasses (six each) suspended by the (a) Achilles tendon at 26 +/- 2 degrees C for 1 h before cutting (b) Achilles tendon at 2-3 degrees C for 42 h and (c) Pelvis at 26 +/- 2 degrees C for 7 h followed by chilling at 2-3 degrees C for 17 h. The muscles were cooked by boiling in a water bath for 30 min or by heating in a pressure cooker for 20 min and the tenderness measured with a Warner-Bratzler tenderometer. Hardness, cohensiveness, elasticity and chewiness were also measured with a General Foods Texturometer. With conventional hanging at 2-3 degrees C the SM muscle was the toughest and the ST muscle the most tender. By holding carcasses at 26 +/- degrees C for 1 h before cooking there was an increased tenderness. The most tender meat was found from carcasses which were suspended by the pelvis at 26 +/- degrees C before chilling. The increase or decrease in shear values were respectively associated with contraction or stretching of muscles effected by carcass conditioning treatments. In contrast, thermal shrinkage due to cooking had opposite effects so that greater thermal shrinkage resulted in lower shear values. The shear values from the Warner Bratzler tenderometer did not correlate well with the parameters measured by the General Foods Texturometer. PMID- 22055574 TI - The rate of metmyoglobin formation in beef, pork, and turkey meat as influenced by pH, sodium chloride, and sodium tripolyphosphate. AB - This study investigated the effects of pH (5.5 to 7.0), sodium chloride concentration (0.0-3.0%), and sodium tripolyphosphate concentration (0.0 and 0.5%) on the rate of metmyoglobin formation in ground beef, pork and turkey meat during refrigerated storage. Increasing the sodium chloride concentration produced a progressive increase in the rate of metmyoglobin formation in ground beef. Increasing the pH between pH 5.5 and 6.5 had no effect on the rate of metmyoglobin formation with ground beef and turkey meat, but produced a marked decrease between pH 6.5 and 7.0. In contrast pH had no consistent effect on the rate of metmyoglobin formation of ground pork and the rate of formation remained low at all pH levels. When ground beef contained 0.5% sodium tripolyphosphate, the effect of pH was reversed and the rate of metmyoglobin formation was lowest at pH 5.5, increased as the pH increased to 6.5 and then plateaued. PMID- 22055575 TI - Colour stability of bovine Longissimus and Psoas major muscle as affected by electrical stimulation and hot boning. AB - From eight electrically stimulated and eight non-stimulated cows the righthand side longissimus and psoas major muscles were hot boned within 1 1 2 h post mortem, vacuum packaged and chilled and storred at 1+/-1 degrees C. Immediately after slaughter, the lefthand carcass-sides were blast-chilled for 1 1 2 h and subsequently chilled at 1+/-1 degrees C until the following day. After cold boning, the longissimus and psoas major muscle were packaged, chilled and stored as the hot boned muscles. After 12 days of storage, steaks, cut from the primals, were displayed at 1+/-1 degrees C under continuous illumination (300-400 lx). Colour measurements after 0, 2 and 4 days of display revealed a significant (p<0.10) effect of time of boning on non-stimulated psoas major muscle (lower values for a (*), b (*) values, chroma and %R630-%R580). Significant effects of electrical stimulation were not observed. Changes in hue tended to be more pronounced when the meat had been stimulated. Changes in chroma were largest (p<0.10) is non-stimulated, hot boned psoas muscle. Analysis of variances showed that in the longissimus muscle significant effects (p<0.10) of time boning and electrical stimulation were present. The effect of time of boning was often influenced by the use of electrical stimulation. Changes in hue and chroma indicated that hot boned samples had a higher colour stability than cold boned controls, especially when the carcasses had not been stimulated electrically. The observed differences in colour stability were rather small in all treatment groups and are not expected to present any practical merchandising problem. PMID- 22055576 TI - Lung proteins: effect of defatting with several solvents and extrusion cooking on some functional properties. AB - Dried lung defatted with several solvents was texturized by extrusion cooking. The emulsifying capacity, water absorption capacity, and protein solubility, at different pH and MgCl(2) concentrations, of this material were determined prior to the after extrusion, as well as the texture profile analysis of the rehydrated extrudates. Solubility profile and emulsifying capacity of the lung proteins varied in relation to the solvent used in their defatting while the water absorption capacity was not affected. The extrusion of these materials promoted a higher solubilization of the protein fraction. The texture parameters of the extrudates studied and the solvent used to defat this material are related, indicating that the lipid-protein complex, left after solvent extraction, may play an important role in the texturization processof lung proteins. PMID- 22055577 TI - Microbiological characteristics of pork chops and ground pork from swine fed a high monosaturated fat diet. AB - Twelve percent high-oleic acid sunflower oil (HOSO) was included in a swine diet to increase the ratio of monounsaturated fatty acids to saturated fatty acids in pork chops and ground pork patties. Aerobic plate counts (APCs) of pork chops prepared from animals on control and HOSO diets did not differ (P >0.05) and no specific pattern of differences in the microflora of pork chops or ground pork patties could be attributed to diet. However, after 4 days of refrigerated storage, APCs of ground pork patties from animals fed the HOSO diet were lower (P<0.05) than those of comparable patties prepared from animals fed the control diet. PMID- 22055578 TI - Some microbiological assays of ground beef blended with hydrogenated soybean oil. AB - Ground beef patties were formulated from beef lean, beef fat and hydrogenated soybean oil. Using the Pearson Square Method, the patties were formed to contain three total fat levels (16,20 and 24%). At each level, vegetable fat was substituted for 0,25 or 50% of total fat to end up with nine different blends. Aerobic psychrotrophs and mesophiles of the blends were investigated at 0-, 3- and 6-day intervals. A split-split plot design with two replications was used to differentiate significant and non-significant attributes of the main effect and the corresponding interactions. Results obtained show that total fat level, percentage vegetable fat or replication did not have a significant effect on bacterial numbers of ground beef extended with hydrogenated soybean oil of 70 iodine value. However, the days of storage significantly (P <0.001) affected both the Standard Plate Count (SPC) and Psychotrophic Plate Count (PPC). The log number of bacteria in both SPC and PPC continued to increase with length of storage. In all the cases studied PPC was found to be higher than SPC, which indicates that the predominant microflora in raw beef products is psychrotrophic in nature. PMID- 22055579 TI - Increase in retail display of frozen lamb chops with increased loin storage time before cutting into chops. AB - There is a steady deterioration of the colour of lamb chops during frozen storage. Storing meat in carcass form or as primals before cutting and packaging minimizes the exposure of the meat surfaces to deteriorating environmental effects. This experiment examines the effects of storage conditions (form, time and temperature) on the display life of frozen chops. Loins were removed from recently frozen carcasses and stored for 0, 10, 20 or 30 weeks at temperatures of -5 degrees C, -10 degrees C and -20 degrees C. Chops were cut from the stored loins, packaged in oxygen permeable film, stored in the dark at -20 degrees C for 0,4,8 or 12 weeks and then displayed at -20 degrees C under continuous lighting. The retail display life of the chops was assessed by an experienced colour panel. The most rapid colour deterioration occurred in chops cut from unstored frozen loins and held for 12 weeks prior to display (display life of less than 1 day). Chops cut from loins stored for 30 weeks at -20 degrees C, and then held for 12 weeks prior to display had a display life of 23 days. Both increased loin storage temperature and an increased duration of chop storage before display decreased the retial display life. This study indicates that frozen storage of cut chops for as little as 4 weeks reduces the display life by almost 80% so that whole carcasses or loins rather than cut chops should be shipped to distant markets. unstored frozen loins and held for 12 weeks prior to display (display life of less. PMID- 22055580 TI - Recommended terminology for the muscle commonly designated 'longissimus dorsi'. AB - Musculus longissimus of the erector spinae is frequently used by meat scientists because of its relative mass, its commercial importance and its variability in quality. Its designation has fluctuated considerably due to confusion over interpretation of accepted anatomical guidelines, some of which have been altered to improve precision. We recommend that meat and muscle scientists refer to the part of the whole muscle they generally use as the Longissimus thoracis et lumborum (LTL) or to either of its two parts, Longissimus thoracis (LT) or longissimus lumborum (LL), depending on which is referenced. The word dorsi should be omitted, the word musculus (or its abbreviation M.) preceding all muscles in Latin should not be used in English, and the longissimus atlantis, capitis and cervicis should not be included except when they are actually used. PMID- 22055584 TI - Perfecting the plate: adding cardioprotective compounds to the diet. PMID- 22055585 TI - Management of patients with pancreatic adenocarcinoma: national trends in patient selection, operative management, and use of adjuvant therapy. AB - BACKGROUND: Surgical resection remains the only potentially curative option for patients with pancreatic adenocarcinoma (PAC). Advances in surgical technique and perioperative care have reduced perioperative mortality; however, temporal trends in perioperative morbidity and the use of adjuvant therapy on a population basis remain ill-defined. STUDY DESIGN: Using Surveillance, Epidemiology, and End Results-Medicare data, 2,461 patients with resected PAC were identified from 1991 to 2005. We examined trends in preoperative comorbidity indices, adjuvant treatment, type of pancreatic resection, and changes in morbidity and mortality during 4 time intervals (ie, 1991-1996, 1997-2000, 2001-2003, and 2003-2005). RESULTS: The majority of patients underwent pancreaticoduodenectomy (n = 1,945; 79%). There was a temporal increase in mean patient age (p < 0.05) and the number of patients with multiple preoperative comorbidities (Elixhauser comorbidities >=3: 1991-1996, 10% vs 2003-2005, 26%; p < 0.001). Perioperative morbidity (53%) did not, however, change over time (p = 0.97) and 30-day mortality decreased by half (1991-1996: 6% vs 2003-2005: 3%; p = 0.04). Overall, 51% (n = 1,243) of patients received adjuvant therapy, with the majority receiving chemoradiation (n = 817; 33%). Among patients who received adjuvant therapy, factors associated with receipt of adjuvant chemotherapy alone relative to chemoradiation included older patient age (odds ratio = 1.75; p < 0.001) and >=3 medical comorbidities (odds ratio = 1.57; p = 0.007). Receipt of adjuvant chemotherapy alone also increased over time (2003-2005 vs 1991-1996, odds ratio = 2.21; p < 0.001). CONCLUSIONS: Perioperative 30-day mortality associated with resection for PAC decreased by one-half from 1991 to 2005. Although patients undergoing resection for PAC were older and had more preoperative comorbidities, the incidence of perioperative complications remained stable. The relative use of adjuvant chemotherapy alone vs chemoradiation therapy for PAC has increased in the United States during the 15 years examined. PMID- 22055586 TI - Phototoxicity and photocarcinogenesis associated with voriconazole. AB - The antifungal voriconazole was given its marketing authorization in 2002. Several kinds of adverse effects have been reported, including acute and chronic cutaneous adverse effects, mainly due to a phototoxicity mechanism. More recently, some authors have reported that voriconazole was involved in the occurrence of multiple and often-aggressive cutaneous squamous cell carcinomas if the treatment was maintained for a long time. According to safety data in studies assessing voriconazole effectiveness, 8% of outpatients may experience phototoxic events. An overview of the different types of phototoxicity and of the concerned population was given by the 61 published case reports of photo-induced voriconazole-related skin adverse events (including 18 cases of squamous cell carcinomas). The most likely mechanisms may be phototoxicity directly related to either voriconazole or to its N-oxide main metabolite, and an interaction with retinoid metabolism; moreover, immunodeficiency may enhance the risk of skin cancer. Several issues remain to be investigated, and studies are needed concerning the phototoxicity and photocarcinogenesis of voriconazole and the prognosis of chronic non-malignant skin lesions. Voriconazole prescription must be associated with strict photoprotection; in case of a phototoxic adverse event, another azole may be recommended. PMID- 22055587 TI - Radiofrequency ablation combined with percutaneous ethanol injection in patients with hepatocellular carcinoma. AB - BACKGROUND AND STUDY AIMS: Hepatocellular carcinoma (HCC) is a major burden on health-care systems worldwide. Although radiofrequency ablation (RFA) is currently considered the best technique for coagulative necrosis, the superiority of concomitant use of RFA and percutaneous ethanol injection (PEI) needs to be determined. The study was designed to compare efficacy, safety and rate of survival of patients with HCC assigned to receive combined PEI-RFA versus RFA alone and versus PEI alone. PATIENTS AND METHODS: This 3-year study enrolled 90 cirrhotic patients with HCC (Child's class A or B, but not class C). They were randomly assigned for either PEI-RFA (group I), RFA alone (group II) or PEI alone (group III). The primary end point was ablation of the tumour. The secondary end point was rate of survival and recurrence. RESULTS: After the first session, complete ablation was significantly higher in the combination group (87.9%) compared with the RFA group (54.54%). After the second session, complete ablation was achieved in 97.0% of the combination group and in 84.8% of the RFA group. Regarding the PEI group, 75% had complete ablation, whereas 25% had partial ablation after multiple sessions. The survival rate, 1.5 years later, was significantly higher in group I (86.7%) compared with group III (63.3%). The overall incidence of serious adverse events was nil. CONCLUSION: Combined treatment is superior to RFA alone and to PEI alone, in safety and efficacy in patients with HCC. PMID- 22055588 TI - Predictors of hepatocyte proliferative activity in chronic hepatitis B and C vs. steatohepatitis as assessed by the monoclonal antibody MIB1-Ki-67. AB - BACKGROUND AND STUDY AIMS: Chronic hepatitis is characterised by increased regenerative cell proliferation, a process that makes cells more susceptible to gene mutations and development of hepatocellular carcinoma (HCC). Evaluation of the proliferative index could be a useful tool for identifying patients at risk for HCC. The current study was planned to evaluate hepatocyte proliferation in predominant causes of chronic liver disease in an attempt to investigate predictors of proliferation. PATIENTS AND METHODS: This study included 84 patients with chronic liver diseases, and they were classified into three groups: chronic hepatitis C (50 patients), non-alcoholic steatohepatitis (NASH) (20 patients) and chronic hepatitis B (14 patients). All cases were investigated by liver function tests, polymerase chain reaction (PCR) hepatitis C virus (HCV) and hepatitis B virus (HBV), routine abdominal ultrasound and liver biopsy with detection of the proliferative index using the monoclonal antibody MIBI-Ki-67. RESULTS: The proliferative index was significantly higher in the chronic hepatitis C group than in the chronic hepatitis B group (P value=0.007). There were significant correlations of the Ki-67 index in both zone 1 and zones 2 and 3 with alanine aminotransferase (ALT), aspartate aminotransferase (AST) and histological activity index (HAI) score. Using the multiple regression analysis on the variables affecting proliferation, it was found that predictors of zone 1 proliferation were the following variables: ALT, age, AST and aetiological factor, in that order. CONCLUSION: HCV aetiology had significantly higher proliferation index, whereas NASH had the least. Increased HAI score is associated with higher proliferative index in either zone 1 or zones 2 and 3. Predictors of proliferation index in zone 1 were ALT, age, AST and aetiological factor. PMID- 22055589 TI - A clinical study of Wilson's disease: The experience of a single Egyptian Paediatric Hepatology Unit. AB - BACKGROUND AND STUDY AIMS: Most paediatric patients with Wilson's disease (WD) present with hepatic manifestations, but some may have neurologic or psychiatric features. Our aim was to define the clinical, biochemical features and the outcome of therapy of a group of Egyptian children diagnosed with WD. PATIENTS AND METHODS: The study was carried out at the Paediatric Hepatology Unit at Cairo University Children's Hospital, Egypt; 54 patients were diagnosed with WD from 1996 to 2009. The diagnosis was based on low serum ceruloplasmin levels, increased urinary copper concentrations before or after D-penicillamine challenge and/or the presence of Kayser-Fleischer (K-F) rings. RESULTS: The clinical presentation was as follows: hepatic presentation in 33 patients (61%), hepato neurologic 3 (5.5%), neurologic 5 (9.3%) and presymptomatic 13 (24%). Twelve couples had more than one affected sib. Increased urinary copper concentrations before or after D-penicillamine challenge was found in all patients, low serum ceruloplasmin in 97% and K-F rings in 31.5%. All patients were treated with penicillamine and zinc sulphate except one presymptomatic case who was treated with zinc sulphate only. Three patients underwent liver transplantation and eight patients died after a median duration of treatment of 6 months (1-36). The hepatic symptoms improved with treatment but the neurological symptoms remained stationary. CONCLUSIONS: Clinical and biochemical assays remain the standard for diagnosis of WD. Penicillamine and zinc therapy can effectively treat WD with hepatic symptoms. Liver transplantation remains life saving for those with fulminant and end stage WD. Screening for presymptomatic sibs is of utmost importance. PMID- 22055590 TI - Serum cystatin C in advanced liver cirrhosis and different stages of the hepatorenal syndrome. AB - BACKGROUND AND STUDY AIMS: The hepatorenal syndrome (HRS) is classified into two types (HRS-2 and HRS-1) based on mild or high serum creatinine elevations. Although it has been identified as an early marker of renal dysfunction, data are lacking about cystatin C across the wide range of renal changes in end-stage liver disease. This study investigates serum cystatin C and creatinine in patients with advanced liver cirrhosis and classic HRS throughout its whole spectrum. PATIENTS AND METHODS: Serum cystatin C immunonephelometric measurements were obtained from 65 Child-Pugh C patients: 32 with normal creatinine, 17 with HRS-2 and 16 with HRS-1. The glomerular filtration rate (GFR) was estimated according to modification of diet in renal disease (MDRD) and the Hoek formulae (creatinine- and cystatin C-based, respectively) with staging of renal dysfunction severity into an increasing order from 1 to 5. RESULTS: Early HRS was identified by the raised cystatin C in 56.3% of patients having normal creatinine. Cystatin C correlated significantly with creatinine in HRS-2 (r=0.74; p<0.001) and showed a significantly lower multiplication ratio (folds of rise) compared to creatinine in HRS-1 patients (p<0.01). There was no satisfactory agreement between MDRD and Hoek GFR staging (k=0.29). CONCLUSIONS: The 'early' HRS identified by a rise in cystatin C in cases with advanced cirrhosis was found to be common and can be added to the already classified two types, as type-3 HRS. Compared to creatinine, cystatin C provides no better information in HRS-2, and underestimates the renal deterioration in HRS-1. Further studies are required to determine the course of the early HRS. PMID- 22055591 TI - Influence of steatosis on progression of fibrosis and virological response in chronic hepatitis C cases. AB - BACKGROUND AND STUDY AIMS: Hepatic steatosis seems to be frequently found histopathologically in chronic hepatitis C virus (HCV)-infected patients. The aim of this study is to determine the influence of steatosis on HCV disease severity (fibrosis) and to evaluate its impact on sustained virological response (SVR) to antiviral therapy. PATIENTS AND METHODS: From April 2008 to April 2010, 148 consecutive adults (87 females (59%) and 61 males (41%); mean age: 55.2 years) with HCV admitted for liver biopsy were included in this retrospective study. At least one element of metabolic syndrome was identified in all cases: Obesity (n=44), hyperlipidaemia (n=40), hypertension (n=29) and diabetes (n=21). Liver fibrosis was classified according to the Metavir score and hepatic steatosis described as following: S0: absent; S1: minimal (<30%); S2: moderate (30-60%); and S3: severe (>60%). Patients were divided into two groups: S0S1 group (absent or minimal steatosis) and S2S3 group (moderate to severe steatosis). Of the 148 patients, 53 were treated with pegylated interferon and ribavirin combination therapy. RESULTS: Steatosis was found in 40 patients (27%): S1 in 72.5%, S2 in 17.5% and S3 in 10% of cases. The distribution of patients according to the degree of fibrosis was as follows: in the S0S1 group, F1=12.4%, F2=36.5%, F3=21.1% and F4=21.1% and in the S2S3 group, F1=9%, F2=45.5%, F3=18.2% and F4=27.3%. There was no difference between the two groups regarding the degree of fibrosis (p>=0.80). The rate of SVR was 64%: 63% in the S0S1 group and 75% in the S2S3 group. The difference was not statistically significant (p=1). CONCLUSION: Steatosis was found in 25% of cases. Liver steatosis in chronic hepatitis C is not a negative prognostic factor of response to combined antiviral therapy. These results must be confirmed by a large series of patients. PMID- 22055592 TI - Evaluation of serum LINE-1 hypomethylation as a prognostic marker for hepatocellular carcinoma. AB - BACKGROUND AND STUDY AIMS: Global hypomethylation is one of the most consistent epigenetic changes in cancer. Development of hepatocellular carcinoma (HCC) must be understood as a multistep process with accumulation of genetic and epigenetic alterations. In the last decades, in addition to genetic alterations, epigenetic changes have been recognized as an important and alternative mechanism in tumourigenesis. We investigated the clinical implications of global hypomethylation in the sera of patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: PCR was used to assess the methylation status of long interspersed nuclear element type 1 (LINE-1) repetitive sequences in genomic DNA derived from sera of 50 patients with HCC, 20 patients with cirrhosis, 20 patients with chronic hepatitis C and 10 healthy subjects. RESULTS: Serum genome hypomethylation was significantly increased in patients with HCC (p<0.001). The levels of serum LINE-1 hypomethylation at initial presentation correlated significantly with tumour size, tumour number and alpha-foetoprotein level. Moreover high serum LINE-1 hypomethylation correlates significantly with poor survival. CONCLUSION: Serum LINE-1 hypomethylation may serve as a prognostic marker for patients with HCC. PMID- 22055593 TI - Improved antifibrotic effect of a combination of verapamil and silymarin in rat induced liver fibrosis. AB - BACKGROUND AND STUDY AIMS: Liver fibrosis progresses to cirrhosis in several settings, for example, severe acute alcoholic hepatitis, and hepatitis C virus (HCV) reinfection after liver transplantation. Cirrhosis produces hepatocellular dysfunction, which is also a risk factor for hepatocellular carcinoma. We studied verapamil as a prophylactic, therapeutic antifibrotic drug alone and in combination with silymarin in experimental rat's liver-induced fibrosis. MATERIAL AND METHODS: Liver fibrosis was induced by intra-peritoneal injection of rats with pig serum 0.5ml twice weekly for 6 weeks, which resulted in score three fibrosis. Prophylactic verapamil alone and silymarin alone and a combination of both were administered at the same time of induction of liver fibrosis and continued for the duration of induction. Therapeutic verapamil was started on the last day of fibrosis induction and continued for 4 weeks. The extent of liver fibrosis was evaluated using Ishak's fibrosis score. Serum alanine aminotransferase (ALT) was measured for follow-up. RESULTS: Compared to fibrotic model rats, prophylactic verapamil, silymarin and combined verapamil plus silymarin significantly resulted in lower serum ALT levels. Prophylactic use of verapamil and silymarin each alone revealed score 2 fibrosis with positive alpha SMA immunostaining; while prophylactic treatment with combined verapamil plus silymarin revealed no fibrosis supported by negative alpha-SMA immunostaining. Verapamil treated fibrotic rat's liver revealed significant regression in liver fibrosis scores with positive alpha-SMA immunostaining. CONCLUSIONS: Verapamil alone has a more significant prophylactic than therapeutic antifibrotic effect against induced liver fibrosis; it was more significant than silymarin. The combination of verapamil and silymarin, showed the best protection through their synergistic antifibrotic effect. PMID- 22055594 TI - Correlation between creatinine clearance and Helicobacter pylori infection eradication with sequential and triple therapeutic regimens: A randomised clinical trial. AB - BACKGROUND AND STUDY AIMS: Uraemic patients show susceptibility to gastrointestinal mucosal lesions and colonisation by Helicobacter pylori (HP). Antibiotic resistance constitutes a problem in treatment and bismuth preparations are toxic in uraemic patients. This study aimed to assess the correlation between creatinine clearance (CrCl) and eradication of HP infection with new sequential and standard triple therapeutic regimens. PATIENTS AND METHODS: A total of 120 HP positive patients with renal function impairment and 60 control patients with HP infection were enrolled in this study. Patients were divided into four groups on the basis of CrCl and were randomly assigned to one of the two different regimens: A 14-day standard triple therapy with 20mg omeprazole bid, 1000mg amoxicillin bid and 500mg clarithromycin bid and a new sequential regimen with 20mg omeprazole bid and 1000mg amoxicillin bid both for 14 days, 500mg ciprofloxacin bid for the first 7 days and 200mg furazolidone bid for the last 7 days. Doses of amoxicillin, clarithromycin and ciprofloxacin were reduced to 50% in the cases of CrCl <30mgdl(-1). RESULTS: One hundred and sixty two out of 180 HP-positive patients (54.3% male, 51.6+/-12.1 years) completed treatment in the four groups and were studied. According to renal function they were classified into group A (n=39), haemodialysis (HD) patients; group B (n=37), CrCl <30mgdl( 1) without HD; group C (n=36), CrCl between 30 and 60mgdl(-1); and group D (n=50), control subjects with CrCl >90mgdl(-1). HP was successfully eradicated in 77.7% of patients with standard triple therapy and in 81.4% of patients with the sequential therapy. There was no significant difference among the study groups in the rate of HP-infection eradication with both regimens. CONCLUSION: HP eradication rates did not differ with both sequential and standard therapeutic regimens in uraemic and non-uraemic patients. We, therefore, prefer the standard triple therapy due to its simplicity and reported. PMID- 22055595 TI - Rupture of a big ovarian cyst and pneumoperitoneum post-colonoscopy and endoscopic mucosal resection. PMID- 22055596 TI - Acanthosis nigricans: A presentation of gastric adenocarcinoma. PMID- 22055597 TI - Upper gastrointestinal bleeding in elderly patients in a Tunisian hospital: A retrospective study. AB - BACKGROUND AND STUDY AIMS: The older age group presents a major problem in the management of acute gastrointestinal bleeding with a relatively high mortality. The study aims to describe the background characteristics, causes and outcome of acute upper gastrointestinal bleeding in the elderly in Tunisia. PATIENTS AND METHODS: We retrospectively reviewed data of 401 patients aged>=60 years presenting with upper gastrointestinal bleeding. Information collected included history, physical examination findings, laboratory data, endoscopic findings and length of hospital stay. Patients were divided into two groups: group A (65-79 years) and group B (>79 years). RESULTS: Group A included 315 patients and group B 86 patients. There was a male preponderance in both groups. Co-morbidity (p<0.01) and use of non-steroidal anti-inflammatory drugs (NSAIDs) or anti platelet drugs (p<0.01) were more common in group B. Oesophagitis was the cause of bleeding in 38.37% in group B, as compared with 19% in group A. The main cause of bleeding in group A was peptic ulcer. Rebleeding (6/86) and emergency surgery (1/86) were rare in group B and not different from those in group A. However, the bleeding-related mortality in the very elderly group was higher (13.9% vs. 4.76%; p=0.02). In multivariate analysis, only shock on admission was independently related to mortality (p=0.02). CONCLUSION: Oesophagitis is the major cause of upper gastrointestinal haemorrhage in the very elderly patients. While rebleeding and emergency surgery rates are relatively low, the bleeding-related mortality was higher in the very elderly group. PMID- 22055598 TI - Mantle cell lymphoma of the colon with massive splenomegaly: A case report. AB - We describe colonoscopic features in a 77-year-old female with relapse of mantle cell lymphoma, who presented with a history of rectal bleeding of 2 months' duration. Her initial colonoscopy 3 years prior to the current presentation had revealed no gross lesions of mantle cell lymphoma; however, there was evidence of microscopic disease at that time as well. The patient had now developed classical lesions following relapse of the disease. The present case report gives the natural history of this rare tumour. The comparative colonoscopic features with a brief review of mantle cell lymphoma are presented. PMID- 22055599 TI - Calcified liver hydatid cyst compressing the gall bladder. AB - A 48-year-old male patient was admitted to suffering from hydatid disease located in the gall bladder. Although Morocco remains an endemic area for echinococcosis, this presentation of the disease was rare. The pericyst was tightly attached to the liver. Complete pericystectomy with cholecystectomy was done. Histopathology confirmed the presence of a calcified hydatid cyst of the gall bladder. Perioperative adjuvant medical therapy with albendazole was administered. After a 2-year follow-up, no recurrence occurred. PMID- 22055600 TI - A new case of solitary true pancreatic cyst. AB - A true cyst of the pancreas is extremely rare, and few cases have been reported in adult patients. The authors report a new case of this rare pathological entity. A 35-year-old male patient was admitted to our unit with a cystic mass, about 6cm in diameter, located in the pancreatic head, in proximity to the duodenum, vena cava, biliary tree and right kidney. Clinical features and imagery were suggestive for a benign neoplasm, as did surgical findings. Cystoduodenostomy was done. Histological finding revealed a cyst lined by cuboidal epithelium without morphologic alterations. Analysis of the cyst fluid showed a high level of CA 19-9 (10,000Uml(-1)). After 1-year follow-up, the patient was found to be doing well without any abdominal symptoms. Ultrasound images revealed no cyst recurrence. PMID- 22055601 TI - Fatal hypoglycaemia from IGF II hyperproduction as a complication of a mesenteric gastrointestinal stromal tumour. PMID- 22055603 TI - Prospective study of soft tissue contour changes following chin bone graft harvesting. AB - This study sought to evaluate changes in the soft tissue contour after chin bone graft harvesting. Thirty selected patients underwent chin bone graft harvesting and evaluations were made using lateral cephalograms preoperatively and postoperatively at 30 and 180 days. Fixed points and lines were established on cephalometric tracings and used to measure the selected vertical and sagittal parameters. Results showed statistically significant alterations to the vertical position values of the vermilion (V-VPV) which increased from 9.70 to 11.01 and the exposure of lower incisors (V-ELI) which increased from 1.85 to 3.5, showing an increase in their distance from the plane of reference and a lowering of their position, the clinical equivalent of a labial ptosis condition. None of the sagittal parameters analysed showed any statistically significant variation in the final evaluation. The study concluded that the alterations to patients' soft tissue contours resulted mainly from failure to ensure precise reattachment of the mentalis muscles and identified the need for further investigation of that aspect. PMID- 22055604 TI - Enzyme levels in raw meat after low dose ionizing radiation and extended refrigerated storage. AB - Bovine semimembranosus muscle samples obtained aseptically 24 h after slaughter were irradiated at 1, 5 and 10 kGy between 0 and 4 degrees C and stored at 2 degrees C to determine effects of low level ionizing radiation on tissue-free enzyme levels. Samples were analyzed after 1, 7, 14 and 28 days of storage. Nonspecific proteolysis was measured using (14)C-hemoglobin as the substrate. For determination of possible effect by irradiation on lysosomal enzymes, acid phosphatase and beta-glucuronidase were measured. Assays for acid phosphatase and hemoglobin proteolysis indicated negative relationship between increasing dose and enzymatic activity. At 10 kGy mean reductions in enzymatic activity were 8% and 42%, respectively, beta-Glucuronidase was not affected at this or at the lower levels of radiation. Correlation between dosage and storage time with enzymatic activity was not significant. PMID- 22055605 TI - Seasonal effects on the patterns of deposition of water, fat and protein in rabbit meat. AB - The effect of season on the patterns of deposition of water, fat and protein and on the changes in the chemical composition of total meat, meat from hind leg and M. longissimus lumboris, was studied in rabbits from 1 to 20 weeks of age. Allometric coefficents changed in a continuous way although changes were more marked in the first weeks of postnatal life. Relative rates of deposition increased for fat and decreased for water and protein throughout the experimental period, irrespective of the season or part considered. There were significant seasonal effects on most of the chemical components that affected the initial values of allometric coefficients, and thier later rates of change, but not the pattern of variation. As a consequence, modification of the chemical composition of meat was also significantly influenced by season, but differences were numerically very small. At birth, meat from rabbits born in summer had a lower content of fat and higher of water and protein than that from rabbits born in other seasons. Rates of deposition in postnatal life determined that the chemical composition tended to be similar to that of rabbits grown in other seasons. A tendency towards a higher degree of fatness in older animals was also observed in this season. PMID- 22055606 TI - Effect of subcutaneous fat and high temperature conditioning on bovine meat tenderness. AB - Effects of subcutaneous fat cover and high temperature conditioning on tenderness of meat were studied using 16 steer carcasses. Longissimus subcutaneous fat cover was completely removed from eight carcasses and the right and left sides were stored at either 0 degrees C or 26 degrees C. After 6 h at 26 degrees C, the sides were transferred to the 0 degrees C room; and after 24 h, all sides were transferred to a 1 degrees C room for the duration of the experiment. Cold temperature and removal of fat cover reduced (P < 0.05) the longissimus muscle temperature at 6, 9 and 12 h post-mortem. The pH of the longissimus muscle was lower (P < 0.05) as the result of high temperature conditioning and fat cover 6, 9 and 12 h post-mortem. Consequently, conditions existed which would have been expected to promote cold shortening, yet high temperature conditioning and fat cover had no consistent effects on myofibrillar fragmentation index, sarcomere length or shear values. PMID- 22055607 TI - Evaluation of live and carcass techniques for predicting beef carcass composition. AB - Fifty beef animals varying in size, age and composition were used to determine the most accurate methods for determining beef composition. Separable and chemical composition of the 9-10-11th rib section and measurements of subcutaneous fat thickness were the most useful for explaining observed variability in carcass composition. For predicting percentage fat in fed steers, composition of the 9-10-11th rib section was the most accurate [coefficient of determination (R(2) 0.85)]. The 9-10-11th rib section was the most accurate and precise technique identified in this study to estimate beef carcass composition across and within all age classes. Specific gravity accounted for 68% of the variation in percentage of carcass fat across all age classes combined; however, specific gravity did not account for a significant portion of the variation within each age class. Deuterium oxide dilution was able to account for 77% of the variation in chemical fat percentage across all age classes combined; however, deuterium oxide dilution was not as effective in accounting for the observed variation in fat percentage within each age class. Ultrasound was found to be an accurate live measure of chemical fat percentage within all age classes combined. PMID- 22055608 TI - The effects of hot-boned fat type, preblending treatment and storage time on various physical, processing and sensory characteristics of nonspecific luncheon loaves. AB - Hot-boned and postrigor fat obtained from pork carcasses (with/without preblending treatment) was used in the production of nonspecific luncheon loaves. Processing and sensory characteristics of the luncheon loaves were evaluated. Loaves made from hot-boned fat were observed to produce higher values for percentage cook yield (P<0.05). Whereas, loaves made from cold-boned fat exhibited higher values for fat and moisture released (g and/or ml). Fat and moisture release increased significantly with time in storage for the cold-boned fat. Hunter-color values were not affected by fat type or preblending treatment. Length of storage affected the Hunter-color a(*) (redness) and b(*) (yellowness) values which decreased with time. Sensory evaluation indicated that all treatments were highly acceptable. PMID- 22055609 TI - Microbiological and sensory characteristics of pork loin chops: Role of intramuscular fat. AB - Pork loin chops of High, Intermediate and Low intramuscular fat were trimmed free of subcutaneous fat and then packaged and stored in polyvinyl chloride (PVC) film for 0-6 days or in high oxygen barrier (HOB) film for 0-28 days at 4 degrees C +/ 1 degrees C. In general, marbling group had no (P > 0.05) effect on the aerobic plate count (APC) and did not result in major differences in the distribution of types in the microflora of pork loin chops. During storage, Pseudomonas spp. became dominant in the microflora of PVC-wrapped chops while Lactobacillus spp. became dominant in the microflora of chops stored in HOB film. Of the sensory characteristics examined, mean surface discoloration and mean overall appearance scores of chops of Low intramuscular fat stored in HOB film were usually lower (P < 0.05) than those of chops of Intermediate and High intramuscular fat. In contrast, marbling group usually had no significant effect on mean surface discoloration and mean overall appearance scores of chops packaged in PVC film. PMID- 22055610 TI - Gender-related differences in clinical characteristics and outcomes in patients with diabetic ketoacidosis. AB - BACKGROUND: Diabetic ketoacidosis (DKA) is 1 of the most common and serious complications of diabetes, and is a significant cause of morbidity and mortality. There is a paucity of data regarding gender-related differences in clinical characteristics and outcomes of patients hospitalized for DKA. OBJECTIVE: The purpose of this study was to assess whether gender plays a role in clinical characteristics and outcome of DKA. METHODS: We performed a retrospective cohort study of patients hospitalized with DKA between January 1, 2003 and January 1, 2010. The outcomes of male and female patients were compared. The primary outcome was in-hospital all-cause mortality. The secondary outcomes were 30-day all-cause mortality and rate of complications: sepsis, respiratory failure, multiple organ failure, stroke, and myocardial infarction. RESULTS: Eighty-nine men and 131 women with DKA were included in the study. Male patients had higher rates of chronic renal failure compared with women (16.9% vs 3.1%; P = 0.001), whereas more women than men received oral hypoglycemic therapy (19.8% vs 9.0%; P = 0.046); women also had higher glycosated hemoglobin levels before admission (11.9% [1.7%] vs 9.9% [2.2%]; P = 0.025). The in-hospital mortality rate was not significantly different for both genders (4.5% in the male group vs 3.8% in the female group; P = 1.0). We did not find significant differences between the 2 groups in the 30-day mortality rate (4.5% vs 6.1%; P = 0.7) or the rate of complications (5.6% vs 6.9%; P = 0.9). Advanced age, mechanical ventilation, and bedridden state were independent predictors of 30-day mortality. CONCLUSIONS: In our study we did not find statistically significant differences in the in hospital mortality, 30-day all-cause mortality, or rate of complications between men and women hospitalized with DKA. However, women with poorly controlled type 2 diabetes mellitus receiving oral hypoglycemic therapy required particular attention and might benefit from earlier introduction and intensification of insulin therapy to avoid DKA. PMID- 22055611 TI - Sustainable equine parasite control: perspectives and research needs. AB - Clinically important equine parasites are ubiquitous in managed horse populations. The traditional approach to parasite control is frequent administration of anthelmintics to all horses on a farm. However, increasing levels of anthelmintic resistance is forcing horse owners and veterinarians to shift this control paradigm. Treatment regimens involving routine deworming of all horses throughout the year are now being replaced by more sustainable approaches, which take in to account the importance of maintaining adequate parasite refugia. The selective therapy principle has been recommended for more than 15 years, but there is limited experience with this approach. The relative magnitude of the faecal egg count for an individual horse is a consistent trait, and this provides a reliable basis for selective therapy. But no studies have evaluated the consequences of selective therapy in the long-term, and such studies are strongly needed to validate this approach. Importantly, it remains unclear how selective therapy may affect the prevalence and intensity of other parasites of significant pathogenic potential (e.g. Strongylus vulgaris), which have become uncommon due to years of intensive chemotherapy. Consequently, a selective approach requires vigilant surveillance of the parasite fauna and intensity. This places a demands for reliable diagnostic tools. Also noteworthy is the fact that the majority of equine nematode parasites are more pathogenic during their larval stages, when they cannot be detected by traditional egg counting techniques. Consequently, parasite-specific diagnostic tools capable of assessing prepatent parasite burdens, and able to differentiate between strongyle species of different pathogenic potentials, would be of great value to the equine clinician. Tools for detecting infections with the tapeworm Anoplocephala perfoliata are laborious, difficult to interpret, and at present there is no established method to evaluate treatment efficacy. Thus, better diagnostic tools are needed for tapeworms as well. Biological control, especially the predacious fungi have demonstrated good potential as an adjunct for strongyle control and such a product could easily have a market in equine establishments. In summary, there is general agreement that the traditional treat-all at frequent interval approach should be abandoned, and that optimal parasite control can be maintained with far fewer anthelmintic treatments. But better diagnostic techniques and more evidence documenting the long-term consequences of selective therapy programs are needed to develop and validate systems for sustainable equine parasite control. PMID- 22055612 TI - Development of cathepsin-L cysteine proteinase based Dot-enzyme-linked immunosorbent assay for the diagnosis of Fasciola gigantica infection in buffaloes. AB - Native cathepsin-L cysteine proteinase (28 kDa) was purified from the excretory secretory products of Fasciola gigantica and was used for sero-diagnosis of F. gigantica infection in buffaloes by Dot-enzyme-linked immunosorbent assay (Dot ELISA). The test detected F. gigantica field infection in these animals with a sensitivity of ~ 90%. No specific IgG antibody binding was displayed by sera obtained from 76 buffaloes considered to be Fasciola and other parasite-free by microscopic examination of faeces and necropsy examination of liver, rumen and intestine. Additionally, sera from 156 Fasciola-free buffaloes, yet infected with Gigantocotyle explanatum, Paramphistomum epiclitum, Gastrothylax spp., Strongyloides papillosus and hydatid cyst were all negative, indicating that F. gigantica cathepsin-L cysteine proteinase does not cross-react with these helminth parasites in natural infection of the host. The data indicated that cathepsin-L cysteine proteinase based Dot-ELISA reached ~ 90% sensitivity and 100% specificity with relation to above parasites in the detection of bubaline fasciolosis. The present Dot-ELISA diagnostic assay is relevant to the field diagnosis of F. gigantica infection in buffaloes. PMID- 22055613 TI - [Methylobacterium podarium isolated in the course of intraocular inflammation]. PMID- 22055614 TI - Auditory word recognition of nouns and verbs in children with Specific Language Impairment (SLI). AB - Nouns are fundamentally different from verbs semantically and syntactically, since verbs can specify one, two, or three nominal arguments. In this study, 25 children with Specific Language Impairment (age 5;3-8;2 years) and 50 typically developing children (3;3-8;2 years) participated in an eye-tracking experiment of spoken language comprehension to compare the dynamics of spoken word recognition for nouns and verbs in Spanish. Listeners' eye movements were recorded as they searched an array of pictures in response to hearing a noun or verb. Results showed significant an animacy effect before the word was finished as images that contain more animate entities attracted their looks which suggest an underdevelopment suppression mechanisms inhibition. Moreover, after word finished all the groups showed differences between nouns and verbs. They were faster in recognizing nouns than verbs and one-argument were recognized faster than two- and three-verb arguments whereas. Children with SLI were slower that their controls and especially in the recognition of three-argument verbs. We suggest that this was due to an incomplete argument structure representation that affects processing times. LEARNING OUTCOMES: (1) As a result of this activity, the participant will be able to describe the differences between adults and children with and without SLI in spoken word recognition of nouns and verbs. (2) As a result of this activity, the participant will be able to describe the animacy effect. PMID- 22055615 TI - Lipid-protein interactions as agents of quality deterioration in intermediate moisture meats: An appraisal. AB - The literature on lipid-protein interactions which lead to loss of solubility, complex formation, chain scission and loss of specific amino acids in intermediate moisture foods is reviewed. This knowledge is used to explain reported observations on the quality and nutritive value of proteins in intermediate moisture meats as well as the conflicting reports on the significance of oxidative rancidity and non-enzymic browning in intermediate moisture food systems. PMID- 22055616 TI - Effect of oxygen- and carbon dioxide-enriched atmospheres on shelf-life extension of refrigerated ground pork. AB - The oxidation of the lipids and myoglobin of ground pork meat stored in oxygen- and carbon dioxide-enriched atmospheres at 1 degrees C has been studied. Elevated oxygen levels (80-100%) depressed myoglobin oxidation, increasing the time to 50% metmyoglobin formation from four to about thirteen days. Twenty per cent carbon dioxide greatly reduced the rate of lipid oxidation, extending the time to reach a TBA number of 5 from five to about twelve days. Tocopherol and ascorbic acids were efficient inhibitors of lipid oxidation but citric acid was not. PMID- 22055617 TI - Thermal inactivation of trypsin inhibitors of soybean preparations added to meat. AB - The activity of trypsin inhibitors was investigated in minced meat in which 30% of meat protein was replaced by soybean preparations (flakes, concentrate, isolate, textured flour). Trypsin inhibitors were determined in 20% suspensions of these soybean preparations. The activity of trypsin inhibitors in soybean preparations added to meat, or suspended in water, appeared to be higher than that of dry products. The heat treatment (70, 80, 90 and 100 degrees C for 15 min) reduced the inhibitor activity in all soybean preparations, both in model meat systems (MMS) and in suspensions. Trypsin inhibitor activity was higher in MMS than in water suspensions of soybean preparations, suggesting that meat components protect trypsin inhibitor proteins against heat treatment. Trypsin inhibitor activity in heated meat model systems was too low to produce unfavourable nutritional effects. PMID- 22055618 TI - Relationship of mitochondria and sarcoplasmic reticulum to cold shortening. AB - Sarcoplasmic reticulum and mitochondria preparations from beef and rabbit muscle were shown to bind and release appreciable quantities of Ca(++). Differences between rabbit and beef muscle in Ca(++) binding and release by SR and mitochondrial preparations were not sufficient to account for the massive shortening in chilled beef as compared to little or no shortening in chilled rabbit muscle. Results substantiate the theory of Buege & Marsh (1975) that cold shortening is related to differences in mitochondrial concentration in red and white muscle rather than to differences in the Ca(++)-accumulating ability of SR. In order to explain the reversibility of cold shortening upon rewarming pre-rigor red muscle, a role for both SR and mitochondria is postulated and discussed. PMID- 22055619 TI - Rigor related changes in mechanical properties (tensile and adhesive) and extracellular space in beef muscle. AB - The tensile and adhesive properties of selected beef muscle strips undergoing rigor mortis are presented at various times post mortem. The changes in these mechanical properties of the muscle correlated well with pH and its rate of fall. Additionally, and perhaps most importantly, the shape of the curves generated over the post-mortem ageing times correlate well with changes in extracellular space. The results are discussed and the conclusion drawn that intrafibre water must be considered as a potentially important third factor, in addition to myofibrillar contraction and connective tissue orientation, in the evaluation of meat tenderness. PMID- 22055620 TI - Electrical stimulation of beef sides. AB - Sides of beef were stimulated with one of three different systems of stimulation a high voltage system (1100 V), a low voltage system (110 V) and an extra low voltage system (45 V). Warner-Bratzler shear measurements indicated that for muscles removed at 1 or 2 h post slaughter and then subjected to conditions which induce cold shortening, the high voltage system was superior to the other two. Warner-Bratzler shear values and taste panel tenderness scores indicated that, for all stimulation treatments, muscles removed from stimulated sides at 22 h post slaughter were more tender than those removed from control sides at the same time. Muscles from sides which had received the high voltage treatment, but not those from sides which had received the other stimulation treatments, were judged by the taste panel to be less juicy than muscles from the control sides. Lower shear values for individual muscles from stimulated sides were usually accompanied by longer sarcomeres and it is suggested that the major effect of electrical stimulation is the prevention of cold shortening. PMID- 22055621 TI - Organochlorine pesticide residues in meat of various species. AB - The quantity of organochlorine pesticides present in pork, rabbit, chicken, turkey and horse meat was determined. Levels of residual pesticide were rather higher in the latter three species than in the former two. They were not closely related to fat content. PMID- 22055622 TI - Attentional modulation of perceptual comparison for feature binding. AB - We investigated the neural correlates of attentional modulation in the perceptual comparison process for detecting feature-binding changes in an event-related functional magnetic resonance imaging (fMRI) experiment. Participants performed a variant of a cued change detection task. They viewed a memory array, a spatial retro-cue, and later a probe array. Their task was to judge whether the cued item had changed between the two arrays. Change type was manipulated to be a color location binding or a color feature change. The retro-cue onset time in the retention interval was manipulated to be early or late. As a consequence of strong inter-item competition, we found strong prefrontal activation for late cues when contrasting the binding-change with the color-change condition. In contrast, we observed a comparable behavioral and neural effect between the two types of change detection when retro-cue was presented early. More importantly, we demonstrated a significant inter-regional correlation between the prefrontal and parietal regions in both binding- and color-change conditions for late cues. In addition, extensive prefrontal-parietal-visual functional connectivity was showed for detecting binding changes in the late-cueing condition. These results support the critical role in prefrontal-parietal-visual functional coupling for resolving strong inter-item competition during the comparison process in the binding-change condition. We provide direct evidence that attention modulates neural activity associated with perceptual comparison, biasing competition in favour of the task-relevant information in order to detect binding changes. PMID- 22055623 TI - Plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G polymorphism and endometrial cancer. Influence of PAI-1 polymorphism on tissue PAI-1 antigen and mRNA expression and tumor severity. AB - Plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism may have significance for PAI-1 expression. High levels of PAI-1 in endometrial cancer patients are associated with a poor prognosis. The objective of this study was to evaluate the PAI-1 4G/5G polymorphism in women with and without endometrial cancer and to analyze the influence of this polymorphism on PAI-1 expression in endometrial tissue. In 423 women (212 patients with endometrial cancer and 211 controls) PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Quantitative real-time RT-PCR assay was used to quantify PAI-1 mRNA and PAI-1 protein levels were quantified by ELISA in tissue extracts from 33 patients with endometrial cancer and from 70 endometrial tissues from control women. The frequency of PAI-1 4G/4G genotype (P=0.010) and the PAI-1 4G allele (P=0.009) was significantly higher in patients than in controls. The frequency of PAI-1 4G allele was significantly higher in patients with stage IB than in those with stage IA (P=0.03). Control women with the 4G/4G genotype had higher endometrial PAI-1 protein (P=0.018) and mRNA (P=0.004) levels than those with the 5G/5G genotype. A significant increase in PAI-1 protein and mRNA was observed in endometrial cancer tissue in comparison with the endometrial tissue from control women (P<0.01). In conclusion, frequencies of the PAI-1 4G allele and 4G/4G genotype were found significantly more often in women with endometrial cancer than in controls. PAI-1 levels in endometrial tissue seem to be associated with PAI-1 4G/5G polymorphism. These findings suggest that the PAI-1 4G/4G genotype may be associated with the risk of endometrial cancer in a Caucasian population. Further studies with a larger number of patients are needed to clarify the influence of this PAI-1 polymorphism in endometrial cancer. PMID- 22055624 TI - Silver nanoparticles to self-assembled films: green synthesis and characterization. AB - In the present paper silver nanoparticle was synthesized by chemical reduction of silver nitrate by oxalic acid in aqueous solution. The nanoparticle film (self assembled; mirror like illumination) on the wall of the clean glass surface was also observed after some days. The synthesized silver particles show an intense surface resonance plasmon band in the visible region at 425 nm. Transmission electron microscopy, selected areas electron diffraction, and UV-visible spectroscopy have been employed to characterize Ag-nanoparticles. The nanoparticle films were also observed using conventional visual and scanning electron microscope (spherical particles and size ranging from 23 to 245 nm). The transmission electron micrograph revealed that the average size of silver nanoparticle were <=10 nm and 21-60 nm, respectively. PMID- 22055625 TI - Cell adhesion on chiral surface: the role of protein adsorption. AB - Chirality is one of the basic, unique, and most appealing features of biological molecules; however, many intriguing chiral phenomena in biological world remains insufficiently revealed yet. In this research, we fabricated chiral surfaces by assembling natural chiral amino acids-cysteine of opposite configurations (D- and L-) onto gold surfaces, respectively, and investigated the adhesion of the L929 fibroblast on them. No significant differences were observed in the density of adherent cells under serum-free culture condition; while in serum-containing condition, significantly more cells adhered on the L-Cys assembled surfaces. This phenomenon suggested that serum protein might play an important role in mediating the selective adhesion of cells on chiral surfaces. Hence, we adopted both radiolabeling and surface plasmon resonance (SPR) techniques to monitor protein adsorption onto the above surfaces. The results evidently showed more proteins adsorbed onto surfaces assembled with L-Cys. We propose that the difference in protein adsorption on chiral surfaces as demonstrated in this paper might not only shed light on the ensuing investigation of bio-related chirality phenomena, but also provide a novel strategy for the rational design and fabrication of novel biomaterials and bio-related devices based on chiral effects. PMID- 22055626 TI - On the mechanism of water holding in meat: The swelling and shrinking of myofibrils. AB - Water holding in meat has, in the past, been rather poorly understood and has not been explained at all in structural terms. A unifying hypothesis for this phenomenon is that gains or losses of water in meat are due simply to swelling or shrinking of the myofibrils caused by expansion or shrinking of the filament lattice. Myofibrils have been observed by phase contrast microscopy, and are seen to swell quickly to about twice their original volume in salt solutions resembling those used in meat processing. Such swelling is highly co-operative. Pyrophosphate reduces very substantially the sodium chloride concentration required for maximum swelling. In the absence of pyrophosphate, swelling is accompanied by extraction of the middle of the A-band; in its presence the A-band is completely extracted, beginning from its ends. We suppose that Cl(-) ions bind to the filaments and increase the electrostatic repulsive force between them. A crucial factor in swelling is likely to be the removal at a critical salt concentration of one or more transverse structural constraints in the myofibril (probably crossbridges, the M-line or the Z-line) allowing the filament lattice to expand. We also point out that water losses in rigor, in the PSE condition and on cooking may well result directly from shrinkage of the filament lattice. PMID- 22055627 TI - Tensile properties of cooked beef in relation to rigor temperature and tenderness. AB - A study of the tensile properties of cooked strips from beef sternomandibularis which had gone into rigor at various temperatures showed no clear relationships with earlier observed variations in shear force with rigor temperature. A consistent feature of the load extension curves was a sudden increase in extensibility at a 'change point' of about 1 kg/cm(2). Some curves, particularly those for strips cooked under restraint, showed a third intermediate extensibility. Evidence points to modification of a myofibrillar component as the reason for the sudden changes. PMID- 22055628 TI - Tissue growth patterns in the carcasses of water buffalo and Friesian crossbred cattle-part 1: Individual muscles and anatomical muscle groups. AB - The left sides of the carcasses of twelve Egyptian buffalo, nine half Friesian (? Friesian x ? Egyptian Baladi) and nine three-quarter Friesian (? x ? half Friesian) bulls, serially slaughtered between 161 and 560 kg for buffaloes and between 176 and 448 kg for cattle, were used to describe the growth and distribution of individual muscles and muscle groups. Genotype-group differences in the relative rate of growth were not significant in 85 of 89 muscles and in 8 of 9 muscle groups. The pooled within-group growth coefficients of individual muscles revealed different increasing growth gradients, i.e. disto-proximal in both limbs, mediolateral in the proximal pelvic limb, from elbow flexors to shoulder flexors in the proximal thoracic limb, caudo-cranial in the trunk and from hypaxial to epaxial muscles around the spinal column. The relative growth was lowest in the distal part of the limbs and highest in the anterior part of the carcass (SMG 7 and 8), with the loin and abdominal muscle groups growing at a rate similar to that of the total muscle. The neck and thorax muscle group grew at a higher rate in Friesian crosses than in buffaloes. Genotype-group differences in the weight of each muscle relative to total side muscle (TSM) were significant in 50 of 89 muscles. Of the 50 muscles (constituting around 59% of TSM), 24 (approximately 44% of TSM) were from the expensive muscle groups. As compared with the most different Friesian cross (base = 100) at equal TSM, buffaloes had higher weight of muscle in the hindlimb (107.5% proximally; 106.3% distally) and forelimb (120.0% proximally: 104.6% distally) and significantly less weight of the muscle groups forming the abdominal wall (79.8%) and connecting the forelimb to the thorax (89.1%) and to the neck (90.7%). The weight of the combined expensive groups was significantly greater in buffaloes than in cattle (maximum difference = 1.8 kg) with a tendency for buffaloes to have relatively less of the tender muscles surrounding the spinal column. PMID- 22055629 TI - Effect of electrical stimulation and cooking temperature on the within-sample variation of cooking loss and shear force of lamb. AB - Electrical stimulation decreased the shear force and increased the cooking loss in seven paired lamb Longissimus dorsi (LD) muscles. This treatment did not have any effect on the within-sample variation. Cooking in 55 degrees , 65 degrees and 75 degrees C water baths for 90 min caused a linear increase in the cooking loss and shear force. There was no stimulation-cooking temperature interaction observed. Cooking temperature also had no effect on the within-sample variation. A possible explanation as to why electrical stimulation did not affect the within sample variation is given. PMID- 22055630 TI - Fiber types in the longissimus muscle from water buffalo and selected domestic beef breeds. AB - The distribution and area of longissimus muscle fiber types from two intact male water buffaloes, one Angus bull and one Charolais bull were evaluated. Only fibers of aerobic-oxidative capacity were present in the muscles of the water buffalo examined. The absence of alphaW fibers may imply some significant and distinct differences in muscle metabolic and functional characteristics. All three fibers types were present in the muscles from the Angus and Charolais bulls. These findings may implicate distinct and unique differences in meat characteristics from water buffalo, such as in organoleptic and/or processing traits. PMID- 22055631 TI - The role of epimysial, perimysial and endomysial collagen in determining texture in six bovine muscles. AB - Epimysium, perimysium and endomysium were purified in high yield by a new extraction method from six bovine muscles of increasing toughness. In each case, the mean perimysial collagen fibre diameter, the total collagen content, the relative proportions of the major collagen types (I and III) and the collagen cross-link content were measured. Correlations were found between both collagen fibre diameter and collagen content of perimysial and endomysial connective tissue and meat toughness. No meaningful link could be made between textural quality of the meat and the relative content of types I and III collagen. Significant differences were seen, however, in both the total heat-stable cross link content and the proportion of heat-stable collagen cross-links relative to heat-labile cross-links present in epimysium, perimysium and endomysiuim and the relative toughness of each muscle. The results are discussed with respect to the role of collagen in determining meat texture and toughness. PMID- 22055632 TI - Tenderness of major muscles from three breed-types of cattle at different times on-feed. AB - Seventy-five steers (9 to 12 months of age) of Angus (n = 25), Brahman (n = 25) and Brahman * Angus (n = 25) breed-types of known history were fed a high-energy diet and five steers from each breed-type were slaughtered after 0, 56, 112, 168 and 224 days on test. At seven days post mortem, the left side of each carcass was fabricated and eight major primals or subprimals were obtained. Steaks were removed from the shoulder clod, strip loin, tenderloin, top sirloin, knuckle, top round, bottom round and eye of round for Warner-Bratzler shear (WBS) determinations and from the strip loin and bottom round for sensory panel evaluations. Steaks from Angus and Brahman * Angus steers were generally more tender than steaks from Brahman steers. Tenderness of steaks from steers of the three breed-types responded to time-on-feed differently: (a) steaks from Brahman steers improved (P < 0.05) in tenderness with increasing time-on-feed for all muscles except the M. psoas major (tenderloin); (b) with the exception of the M. longissimus muscle (strip loin), the tenderness of steaks from Angus steers did not change (P > 0.05) as time-on-feed increased and (c) for the Brahman * Angus steers, five of the ten muscles studied improved (P < 0.05) in tenderness with increasing time-on-feed. 'Acceptable' tenderness (WBS values of less than 4.5 kg) for most of the muscles was achieved at feeding periods from 112 to 224 days for Brahman, from 0 to 56 days for Angus and from 56 to 168 days for Brahman * Angus. PMID- 22055633 TI - Characterization of cutability and palatability attributes among different slaughter groups of beef cattle. AB - Fifteen slaughter cattle from five groups (Charolais crossbred bulls, Brahman crossbred steers, Holstein steers, mixed-Exotic crossbred heifers and Hereford Angus crossbred steers) were randomly selected from a commercial feedlot. Time-on feed was 108, 114, 102, 108 and 145 days for the aforementioned groups, respectively. Carcasses from Charolais crossbred bulls had the highest percentage yield of chuck and round, but the lowest percentage yield of loin; hereford-Angus crossbred steers had the lowest percentage yield of round and Holstein steers had the lowest percentage yield of rib. Carcasses from Charolais crossbred bulls had the highest percentage yield of major retail-ready subprimals and lean trim, Hereford-Angus crossbred steers had the highest percentage yield of fat trim and Holstein steers had the highest percentage yield of bone from the major wholesale cuts. Mean percentage yields of closely trimmed, boneless retail cuts were highest for carcasses from the bulls and lowest for carcasses from the Hereford Angus steers. Although Holstein steer carcasses had less fat trim than Brahman crossbred steers mixed-Exotic heifers, this advantage was largely offset by their higher percentage of bone. Loin steaks from carcasses of Charolais crossbred bulls, Holstein, mixed-Exotic heifers were comparable (P > 0.05)with those of Hereford-Angus steers for shear force and sensory panel tenderness ratings. However, loin steaks from carcasses of Brahman-crossbred steers had significantly higher (P < 0.05) shear force values (least tender) and lower (P < 0.05) tenderness and overall palatability ratings. No diffeerences (P > 0.05) were found for flavor desirability of loin steaks among any of the groups. For bottom round steaks, Hereford-Angus steers received the highest palatability ratings while those from Holstein steers received the lowest palatability ratings. PMID- 22055634 TI - Electron microscopic studies of artificial supramolecular structures from collagen solutions. AB - Changes in the molecular structure of collagen fibrils isolated from solutions of native tropocollagen (TC) and of soluble collagen, obtained by enzymic (ESC) and alkaline-salt (ASC) methods, were studied by electron microscopy. It was found that, under certain conditions, it is possible to derive native-like fibrils (NF), segments with long spacings (SLS) and fibrils with long spacings (FLS)_from collagen solutions, these being very similar to structures precipitated from TC. Despite the fact that more structures with clear cross-striations can be isolated from ESC than from ASC, neither enzymic nor alkali-salt treatments cause substantial changes in the molecular structure of solubilized collagen, this determining its orderly aggregation. The data obtained permit the recommendation of new artificial materials for food and medical uses. PMID- 22055635 TI - Believing is the first step to achieving. PMID- 22055636 TI - Practice change in long-term care facilities in Ontario: views of managers and staff. AB - Little is known about how the use of data and feedback influences change in long term care, and that was the focus of this study. Semistructured interviews were conducted with 126 frontline staff and managers from 19 randomly selected Ontario long-term care facilities. Content analysis revealed that staff members use data for problem identification and solution finding, justifying change, and monitoring change. Frontline providers primarily provided resident-based examples of data and feedback processes, whereas managers mainly described organization based examples. Few participants discussed how information from mandated databases and related feedback processes could be used to inform change. Knowledge gained from this study will help organizations better understand the perspectives of different team members about data and feedback, thereby informing interventions that will enhance resident outcomes and quality service delivery in long-term care. PMID- 22055637 TI - Home health and hospice face-to-face encounter visits. PMID- 22055638 TI - Polypharmacy: when is enough, enough? PMID- 22055639 TI - Depression and sleep disturbance in patients with chronic obstructive pulmonary disease. AB - The goal of this study was to examine the unique contributions of sleep disturbance to depression in patients with chronic obstructive pulmonary disease (COPD) after controlling for other contributing variables, including patient characteristics, self-efficacy, and physical activity. One hundred thirty-one outpatients diagnosed with COPD from 3 hospitals in South Korea participated in the study. Data were collected from March to June 2010 and analyzed with descriptive statistics, Pearson correlation, and hierarchical multiple regression using the SPSS WIN program. The level of depression reported in this study was 13.84. Sleep disturbance, not living with a spouse, and self-efficacy were all predictors of depression and accounted for 45% of the variance. These findings show the need to screen routinely for sleep disturbance in patients with COPD and support potential benefits of interventions to enhance self-efficacy and quality of sleep in reducing depression in COPD patients. PMID- 22055641 TI - Advanced practice nurses' perspectives on the use of health optimization strategies for managing chronic disease among older adults in different care settings: pushing the boundaries of self-management programs. AB - This study examines the intention of advanced practice nurses (APNs) to utilize health optimization programs (HOPs) for addressing clients' chronic disease in various work settings (i.e., nursing homes or other care settings). A paper-based survey was administered to 270 APNs at a continuing education conference to determine their intentions to refer patients to HOPs for chronic disease management. APNs working in nursing homes were 0.23 times as likely to utilize HOPs for management of their patients' chronic disease compared with their counterparts working in other care settings (odds ratio = 0.23, confidence interval = 0.06-0.80, P = .021). APNs who had previously used a HOP for management of their patients' chronic disease were 5.2 times as likely to do so again relative to those who had not previously used a HOP for management of their patients' chronic disease (odds ratio = 5.17, confidence interval = 1.78-14.99, P = .002). Educational and organizational interventions are recommended to disseminate further HOPs for chronic disease in nursing home settings as part of an overall health optimization strategy. PMID- 22055640 TI - Profile of nursing home residents with dementia who require assistance with mouth care. AB - The majority of nursing home residents require assistance with activities of daily living, including oral care. Poor oral health is common in the nursing home because residents are not given appropriate assistance to support this aspect of their care. The purpose of this study was to describe the demographic, functional, and behavioral profile of nursing home residents with dementia who require verbal or physical assistance with mouth care. Residents who required verbal support to complete mouth care exhibited higher levels of physical function, higher levels of cognitive functioning in the domains of language and executive function, lower levels of passivity, and higher scores for the personality trait of openness than residents who required physical assistance. Best practices for implementing verbal and physical assistance during mouth care to persons with dementia are presented on the basis of these profiles. PMID- 22055642 TI - Developing a self-reported tool on fall risk based on toileting responses on in hospital falls. AB - The aim of this cohort study was to determine the predictive value of a 2-item self-reported questionnaire regarding in-hospital toileting behavior for predicting falls in older inpatients and to compare its performance with an existing state-based falls assessment scale. Between May 28, 2009 and January 30, 2010, we assessed aged care inpatients for risk of falls using the standard STRATIFY fall screening tool and the 2-item self-reported questionnaire developed for this study. The participants were then followed up, with the primary outcome being the occurrence of falls. Results indicated that participants who were unable to answer the 2-item questionnaire appropriately or sensibly were 14.1 times (confidence interval [CI]: 4.4-45, p <. 001) to 17.0 times (CI: 6.7-43, p < .001) more likely to fall than those who gave an appropriate negative or positive answer. Participants who were assessed to be at high risk of falls on the STRATIFY scale were 9.5 times (odds ratio: 9.5, CI: 1.3-72, p = .03) more likely to fall than those who were low risk. In conclusion, a simple bedside questionnaire regarding patients' toileting behavior with a careful appraisal of answers for appropriate and inappropriate answers may be used as a quick screening tool of fall risk. PMID- 22055643 TI - Aseptic loosening of the patellar component at the cement-implant interface. AB - We present four cases of aseptic loosening at the implant-cement interface following patellar resurfacing. All patients initially had good results, but then presented with onset of a new anterior knee pain. The radiographs including flexed lateral and skyline view of the knee were normal in all the cases. After carefully ruling out infection, aseptic loosening at the cement-implant interface was diagnosed on further investigation. Aseptic loosening of the patellar button at the implant-cement interface can be difficult to diagnose with standard knee radiographs. During flexed lateral radiograph of the knee and the skyline view radiograph of the patellofemoral joint, the patella is compressed on the femur and thereby reducing the loose patellar button. This phenomenon has not been previously described. Patients presenting with new onset of knee pain after an initial good results following patellar resurfacing require further investigation to exclude loosening at the cement-implant interface as plain radiographs can be misleading. PMID- 22055644 TI - Microbiological and sensory characteristics of beef loin steaks: Role of intramuscular fat. AB - Beef loin steaks of different grades (Prime, Choice and Good) were packaged and stored in polyvinyl chloride (PVC) film for 0-6 days and in high-oxygen barrier (HOB) film for 0-28 days. Grade had no significant effect (P > 0.05) on the aerobic plate count and did not result in major differences in the distribution of types in the microflora of steaks. Of the sensory characteristics examined, mean surface discoloration and mean overall appearance scores of Prime and Choice steaks packaged and stored in HOB film often were higher (P < 0.05) than those of Good steaks. Differences in metmyoglobin formation among steaks from the three grades were attributed to differences in the inherent characteristics of the muscles; muscle fibers from Prime and Choice samples were probably more red (as evidenced by greater marbling ability), while muscle fibers of Good samples were probably more white (as evidenced by lesser marbling ability). Red muscles have greater cytochrome activity, which will help reduce metmyoglobin to myoglobin in the absence of oxygen. PMID- 22055645 TI - Comparison of the microbial populations of retail beef and pork. AB - Retail samples of beef mince, beef rump, pork mince and pork rump were enumerated for total plate count, coliforms, Escherichia coli, Staphylococcus aureus, Salmonella and Trichinella spiralis. Total plate counts were similar for all samples; however, the populations of coliforms and Staphylococcus aureus were higher in minced meats than in rumps (P < 0.05). Minced pork was found to carry higher loads of Staphylococcus aureus than any other meat (P < 0.05). Salmonella and Trichinella spiralis were not detected in any sample. PMID- 22055646 TI - The effect of bone in meat samples upon analytical results for fat, protein and water by foss Super-Scan type 10600. AB - Investigations have been made into possible spectral interferences at fat, protein and water wavelengths of the Super-Scan (infra-red meat analyser) due to absorbance by phosphorus (a natural constituent of bone) at the carbohydrate wavelength. Instrument calibration for boneless meat resulted in the need for correction factors to results for bone-in meat of * 0.96, * 1.05 and * 0.97 for % fat, % protein and % water, respectively, to bring them in line with those by standard chemical methods. Comparisons between Super-Scan results for boneless meat to which tricalcium phosphate (the major constituent of bone) has been added showed an interference proportional to the amount of phosphate present and varied in size depending on sample fatness. Calibration with bone-in meat controlled interference adequately for % fat and % water, but still required an empirical correction factor of * 0.97 for protein. PMID- 22055647 TI - The use of filter paper to estimate drip loss of porcine musculature. AB - Two simple, accurate, rapid and economical methods for determining variations in drip loss of lean, prepackaged, post-rigor porcine musculature during storage have been developed. Laboratory grade filter paper having a 45 mm diameter was placed on the cut surface of the muscle (after 10-15 minutes' exposure) and scored for wetness (0 to 5) within 3 s or weighed for fluid accumulation. The tests on 40 randomly selected longissimus muscles that appeared to represent 'normal' quality characteristics proved to be nearly perfectly and positively correlated to % 48 h drip loss. Statistically, the relationship was non curvilinear and, when regression equations were used to predict drip losses on a separate group of 27 muscles having considerable variation in quality, the correlations between the predicted and actual values were nearly perfect (r = 0.97 for score and 0.95 for weight). These two methods have not been compared to other, more sophisticated, ones currently used, but the results of this investigation suggest that the two methods may be useful to the meat industry, especially for practical applications. PMID- 22055648 TI - Tenderization of beef with bacterial collagenase. AB - The feasibility of using a purified collagenase produced by Clostridium histolyticum as a meat tenderizer was studied. Experiments were conducted with enzymes in model systems to compare collagenase with the currently used plant proteinases, papain, bromelain and ficin. Collagenase was shown to have a greater activity in hydrolyzing insoluble collagen than salt-soluble-protein (SSP) and highest activity between 40 degrees and 60 degrees C, with little to no activity above 60 degrees C. Collagenase was added to raw steaks and steaks were placed in bags and cooked in a water bath to 6.5 degrees C. Tenderness was evaluated by analyzing components of Warner-Bratzler shear-deformation curves. The results suggested that addition of NaCl or a combination of CaCl(2), NaCl and collagenase would cause equivalent tenderization. The lack of a significant tenderization due to collagenase could be related to a lack of sensitivity in the shear evaluation or an effect on the enzyme activity due to the meat environment. PMID- 22055649 TI - Some observations on protein changes in washed myofibrils of bovine muscle. AB - It was found that the protein and water contents of washed myofibrils obtained from bovine longissimus dorsi muscles vary with the rate of pH change during the first hour post mortem. Neither myosin nor actin is responsible for the variation, which is due to changes in the other myofibrillar components. The amount of remaining myofibrillar proteins (RMP), obtained after the sum of myosin and actin is deducted from the total myofibrillar protein (TMP), shows a minimum at a rate of pH change corresponding to a 1-h pH value of 6.7. Apart from this pH dependent decrease, a further substantial reduction of the RMP fraction was observed, particularly in myofibrils extracted from electrically stimulated muscles. It is considered that the observed changes result from partial proteolysis taking place in muscle during the early hours post mortem. A possible involvement of connectin as a primary substrate for the action of calcium activated neutral protease is discussed. On the basis of the observed correlation between Warner-Bratzler peak shear force and TMP, a significant influence of pre rigor muscle status on meat tenderness is suggested. PMID- 22055650 TI - Observations on the 3-methylhistidine content of bovine, ovine and porcine muscles. AB - The titres of 3-methylhistidine in bovine and ovine masseter/malaris muscles are similar to one another but low in relation to other skeletal muscles, whereas titres in porcine masseter/malaris resemble the latter. The process of mastication in bovines by masseter/malaris muscles appears to involve prolonged, slow action since the fibres are exclusively of type I. These 'red' fibres have very low titres of 3-methylhistidine in their myosin but normal values in their actin. PMID- 22055651 TI - Anatomical variation and morphology in the position of the palatine foramina in adult human skulls from Greece. AB - OBJECTIVE: To investigate the anatomical variability of the palatine structures in Greek population. MATERIAL AND METHODS: 71 Greek adult dry human skulls were examined to detect the position of the greater palatine (GPF) and lesser palatine foramina (LPF) related to adjacent anatomical landmarks. RESULTS: The perpendicular distance of the GPF to the midline sagittal suture was 1.53 cm and 0.3 cm from the inner border of the alveolar ridge. The mean distance from the posterior palatal border was consistent 0.46 cm on the right and 0.47 cm on the left side of the skulls. In the greater majority of the skulls (76.2%), the GPF were between proximal-distal surfaces of the 3rd maxillary molar. A single LPF was observed in 53.45% of the skulls, two LPF were observed in 31% of the skulls bilaterally and five LPF were rare (2.1%). The commonest position of LPF was at the junction of the palatine bone and the inner lamella of the pterygoid plate (71.9%). CONCLUSION: Our results can help clinicians localize the palatine foramina in patients with and without maxillary molars and to predict the depth of a needle to anaesthetise the maxillary nerve with greater success when performing surgical procedures in the hard and soft palate. PMID- 22055652 TI - MicroRNAs in viral gene regulation. PMID- 22055653 TI - Clinical and neurobiological correlates of soluble amyloid precursor proteins in the cerebrospinal fluid. AB - BACKGROUND: According to a widely accepted hypothesis, the amyloid precursor protein (APP) is processed by two competing pathways: the amyloidogenic beta secretase-mediated pathway or the nonamyloidogenic alpha-secretase-mediated pathway. APP is cleaved preferentially through the nonamyloidogenic pathway in normal brain, whereas the balance shifts to the amyloidogenic pathway in Alzheimer's disease (AD). The levels of the alpha-secretase-cleaved soluble APP (sAPPalpha) and beta-secretase-cleaved soluble APP (sAPPbeta) in cerebrospinal fluid (CSF) are likely to reflect these competing mechanisms. METHODS: We investigated the levels and the relationship between sAPPalpha and sAPPbeta in the CSF of 64 patients with mild AD, 76 patients with mild cognitive impairment, and 12 cognitively healthy control subjects, as well as the effect of apolipoprotein E genotype and sex on soluble APP levels. RESULTS: There was a significant positive correlation between sAPPalpha and sAPPbeta levels in all three groups. sAPPalpha and sAPPbeta concentrations were higher in patients with mild cognitive impairment compared with patients with AD. In the AD group, females exhibited higher sAPPalpha and sAPPbeta levels than males. No influence of the apolipoprotein E genotype on soluble APP concentrations was detected. DISCUSSION: The positive correlation between sAPPalpha and sAPPbeta challenges the hypothesis that AD is caused by an imbalance of the alpha- and beta-secretase APP proteolysis through competing mechanisms. Moreover, the differences in CSF levels of sAPPalpha and sAPPbeta between male and female patients with AD may reflect a "sexual dimorphism" in the activity of the two APP processing pathways in AD. PMID- 22055655 TI - Antimicrobial prophylaxis in women with recurrent urinary tract infections. AB - Recurrent urinary tract infections (UTIs) in women are common, result in considerable morbidity and expense, and can be a management problem for clinicians. Behavioural changes can be useful antimicrobial-sparing measures in the prevention of recurrent UTIs, but antimicrobial prophylaxis may be necessary in those who continue to have recurrences. Continuous prophylaxis, post-coital prophylaxis and intermittent self-treatment with antimicrobials have all been demonstrated to be effective in the prevention of recurrent uncomplicated UTIs. The decision as to which approach to use depends upon the frequency and pattern of recurrences and willingness of the patient to commit to a specific regimen. The risk of adverse events, including antimicrobial resistance, patient's lifestyle and compliance and plans for a pregnancy also need to be considered. The choice of antimicrobial should be based upon the susceptibility pattern of the organisms causing the patient's previous UTIs and history of drug allergies. PMID- 22055654 TI - Cognitive impairment in nondemented oldest-old: prevalence and relationship to cardiovascular risk factors. AB - OBJECTIVE: To determine the prevalence and types of cognitive impairment in a sample of nondemented participants aged >=90 (the oldest-old) and to examine the relationships between cognitive impairment and cardiovascular risk factors. PARTICIPANTS: The participants were 420 nondemented individuals from The 90+ Study, a study of aging and dementia in the oldest-old. These participants were categorized into four nonoverlapping groups: normal cognition, amnestic mild cognitive impairment (aMCI), nonamnestic MCI (naMCI), and other cognitive impairment (OCI). History of cardiovascular risk factors was assessed through self-report. RESULTS: The overall prevalence of cognitive impairment in nondemented participants was 34.0% (95% CI: 29.5-38.5). The prevalence of OCI was highest (17.4%; 95% CI: 13.9-21.4), followed by aMCI (8.3%; 95% CI: 5.9-11.4) and naMCI (8.3%; 95% CI: 5.9-11.4). Normal cognition was present in 66.0% (95% CI: 61.2-70.5) of participants. History of hypertension and stroke were the only risk factors that varied between the groups, occurring more frequently in participants with naMCI (chi(2) = 3.82; P < .05) and OCI (chi(2) = 5.51; P < .05). CONCLUSIONS: This study found a high prevalence of cognitive impairment in a sample of nondemented oldest-old. We did not find a strong relationship between cardiovascular risk factors and the cognitive impairment groups, other than between hypertension and naMCI and stroke and OCI. Future studies comparing the incidence of dementia in these groups will ultimately determine their predictive utility in the oldest-old. PMID- 22055656 TI - Extreme selenium and tellurium contamination in soils--an eighty year-old industrial legacy surrounding a Ni refinery in the Swansea Valley. AB - Elevated levels of selenium (maximum 200 mg/kg) and tellurium (maximum 11 mg/kg) are reported in topsoils (<5 cm) from around a long-established nickel refinery at Clydach in the Lower Swansea Valley, UK. Se and Te are correlated with each other and when these data are plotted as contour diagrams they show a concentric pattern centred on the refinery site. The origin of the Se and Te contamination is investigated. A review of the changes in the refinery practices at the site is presented and used to link the soil contamination to industrial pollution which took place over 80 years ago. The most recent air quality data available cannot rule out some Se contamination up to 2003. PMID- 22055657 TI - Modelling phosphorus dynamics in multi-branch river systems: a study of the Black River, Lake Simcoe, Ontario, Canada. AB - High rates of nutrient loading from agricultural and urban development have resulted in surface water eutrophication and groundwater contamination in regions of Ontario. In Lake Simcoe (Ontario, Canada), anthropogenic nutrient contributions have contributed to increased algal growth, low hypolimnetic oxygen concentrations, and impaired fish reproduction. An ambitious programme has been initiated to reduce phosphorus loads to the lake, aiming to achieve at least a 40% reduction in phosphorus loads by 2045. Achievement of this target necessitates effective remediation strategies, which will rely upon an improved understanding of controls on nutrient export from tributaries of Lake Simcoe as well as improved understanding of the importance of phosphorus cycling within the lake. In this paper, we describe a new model structure for the integrated dynamic and process-based model INCA-P, which allows fully-distributed applications, suited to branched river networks. We demonstrate application of this model to the Black River, a tributary of Lake Simcoe, and use INCA-P to simulate the fluxes of P entering the lake system, apportion phosphorus among different sources in the catchment, and explore future scenarios of land-use change and nutrient management to identify high priority sites for implementation of watershed best management practises. PMID- 22055658 TI - Chemical composition and quality attributes of goat meat and lamb. AB - Chemically, goat meat had significantly (P < 0.05) less intramuscular fat and significantly (P < 0.001) more moisture than lamb. The sarcoplasmic protein concentration of the goat meat was significantly (P < 0.001) greater than that of lamb while the myofibrillar protein concentration was similar in the two species. Goat meat was darker red in colour than lamb. It had significantly (P < 0.001) superior water-holding capacity and less cooking losses than lamb. Meat flavour was significantly (P < 0.05) less strong in goat meat than in lamb. PMID- 22055659 TI - Influence of breeding systems on pH and histochemical properties of muscle fibres in porcine M. semimembranosus. AB - The purpose of this study was to investigate pH values, fibre type frequency and histological features of Semimembranosus muscle of 15 pigs subjected to three breeding systems. The A group was raised in a large paddock; the B group animals were raised in a collective pen until they reached a live weight of 120 kg and then in the same paddock as the A group; the C group was raised in a collective pen. Breeding systems had no significant effect on pH values and fibre type frequency. Histopathological changes in muscle fibres and connective tissue were observed in 12 of the animals studied regardless of the group. However, analysis of the incidence of alterations showed a higher frequency of lesions in the B group, followed by the C group. Except for one case of DFD meat, muscle alterations were not associated with an adverse pH. In addition, regenerating fibres, with strong reactivity for neonatal serum, were observed both in apparently healthy and in pathological muscle samples. PMID- 22055660 TI - Muscle composition of steers treated with the beta-agonist, cimaterol. AB - The effect of the beta-adrenergic agonist, cimaterol, on the nature and amount of collagen in three individual muscles (Longissimus dorsi, Vastus lateralis and Semitendinosus) from young steers was investigated. beta-Agonist-treated animals showed similar rates of liveweight gain to those of control animals but the weight and protein content of the Longissimus dorsi and Vastus lateralis muscles were significantly increased (muscle weights 1216 versus 1494 g, P < 0.05; 514 versus 642 g, P < 0.01, respectively, for control and cimaterol animals). The Semitendinosus muscle, however, showed no significant increase in weight or protein content (P > 0.05). The total collagen content and the proportion of heat soluble collagen varied considerably between muscles, but no significant muscle * treatment interactions were detected (P > 0.05). Cimaterol treatment reduced total muscle collagen content (controls 15.2, cimaterol 12.5mg/g fresh tissue, P < 0.05) and also reduced the percentage of heat-soluble collagen (controls 18.9%, cimaterol 13.0%, P < 0.05). PMID- 22055661 TI - Effect of vacuum-packaged frozen storage, after cooking, on the phospholipids of Hereford and Bison. AB - Changes in the neutral lipid (NL), phospholipid (PL) and their fatty acid (FA) profiles in lean samples of cooked and cooked, vacuum-packaged, frozen (28 days) Hereford and Bison L. dorsi muscle were analyzed. Samples from Herefords contained more saturated fatty acids (SFA) in the neutral lipid fraction than Bison. Storage decreased the C(18:2), C(18:3), C(20:1) and C(20:4) content of the NL. Bison samples contained more total PL and phosphatidylethanolamine (PE) than Hereford. Storage decreased the content of the least polar of the PL which were eluted in the solvent front (fraction 1), phosphatidylinositol (PI), phosphatidylserine (PS), PE and sphingomyelin (SPH). In the combined PL fraction, there were no differences in the FA profile of Bison and Hereford. Storage resulted in a decrease in the content of C(18:2), C(20:4), unsaturated fatty acid (UFA) and polyunsaturated fatty acid (PUFA) in the combined PL fraction. In the PE fraction, Bison samples contained more C(20:4) and PUFA than Hereford. Storage had no effect on the FA profile of PE. The LPC fraction of Bison samples contained more saturated SFA, UFA and PUFA than Hereford, and with storage these FA decreased. Cooked frozen storage also decreased SFA, UFA and PUFA in PC/LPE. PMID- 22055662 TI - Quantitative determination of myoglobin and haemoglobin in beef by high performance liquid chromatography. AB - Three different HPLC columns were tested for their suitability for the analysis of myoglobin and haemoglobin in beef. Complete separation of the two proteins was obtained with an anion exchange column and a column based on hydrophobic interaction. With the latter column a recovery close to 100% was obtained for both proteins when they were added to meat extracts. For both proteins, the standard error of the mean for repeated analyses of ground beef was less than 2% of the detected amount. The method is considered as suited for quantitative routine analysis of myoglobin and haemoglobin in beef and beef products. PMID- 22055663 TI - Variation in haem pigment concentration and colour in meat from British pigs. AB - Variation in chemically determined total haem pigment concentration and instrumentally determined colour was examined in 223 samples of M. longissimus dorsi (LD) representative of the majority of slaughter pigs currently produced in the UK. Whether pigs were sired by White (Large White or Landrace) or Meat-line boars did not affect any measured characteristic but source breeding company influenced total haem pigment concentration (P < 0.01). Haem pigment concentration was higher in muscles from gilts, compared with castrates, boars being intermediate. Gilts also had darker muscles, based on EEL Reflectance values (P < 0.05), and lower hue values (P < 0.05). When compared with animals fed ad-libitum, restricted-fed pigs had higher concentrations of muscle haem pigment (P < 0.001) and this resulted in meat that was slightly darker (P < 0.05), despite having lower ultimate pH (pHu) (P < 0.05), and had a lower hue value (P < 0.001). Measurements of reflectance, total soluble protein and pHu indicated that differences in the incidence of potentially pale, soft, exudative or dark, firm, dry muscle were unlikely to be important contributors to variation in the colour of the meat in this study. PMID- 22055664 TI - Calpains and calpastatin distribution in bovine, porcine and ovine skeletal muscles. AB - The concentration of calpain II and calpastatin was determined in various beef, lamb and pork muscles showing very different metabolic and contractile types as assessed by measurement of lactic dehydrogenase (LDH), citrate synthetase (CS) and ATPase activities. The calpain II: calpastatin ratio, which is a good index of the efficiency of this proteolytic system, was also determined. A species comparison revealed that while calpastatin level was lowest in pork, the ratio of calpain II to calpastatin was highest in this species. For both determinations, lamb was intermediate followed by beef. Conversely, the amount of calpain II was very similar in the three species. In beef and pork, calpain II content decreased as muscle ATPase and LDH activities rose; and conversely increased with CS activity; whereas in lamb, the amount of this enzyme was highest in red muscles regardless of their speed of contraction. Except for masseter muscle, a comparable distribution was observed for calpastatin in beef and pork muscles. In lamb, the calplastatin concentration was highest in slow-twitch red muscles, intermediate in fast-twitch red muscles and lowest in fast-twitch white muscles. Variability of the calpain II: calpastatin ratio with muscle ATPase, LDH and CS activities appeared to be both muscle and species dependent. As results for masseter muscle are rather unexpected, especially in beef and lamb, this muscle was considered separately. The present findings are discussed with regard to the conditioning rate of meat from different species and, within one species, from different muscles. It was concluded that the conditioning rate may be correlated positively to calpain II: calpastatin ratio and negatively to calpastatin content. In contrast, no relationship seems to exist between meat ageing rate and calpain concentrations. PMID- 22055665 TI - Beef tenderness and sarcomere length. AB - A wide range of muscle glycolytic rates was produced in 60 beef carcasses by applying different forms and periods of electrical stimulation immediately after decapitation; a further seven carcasses were not stimulated. The sides were subjected to normal chilling, and at 48 h one short loin per carcass was taken for tenderness evaluation and determination of sarcomere length (SL). In the 19 relatively slow-glycolysing loins-those of 3-h pH (pH(3)) above 6.3-tenderness extended over almost five panel units on a 1-8 scale, and included both the tenderest two and the toughest 10 muscles of the entire study. In the 48 loins of pH(3) below 6.3, on the other hand, tenderness ranged over only 2.5 units, and on average was a full panel unit higher than that of the high-pH(3) muscles. The most striking difference between the two groups, however, was in the relationship between toughness and shortening; the correlation of panel tenderness on SL was remarkably high in the slow glycolysers (r = 0.84), but negligible in those of faster pH decline (r = 0.16). Thus although shortening occurred to about the same extent and over the same range in both groups, it influenced tenderness and tenderness variability only when glycolysis was quite slow. A loin pH(3) of below 6.3, however, is unusual in non-stimulated carcasses, so slow glycolysis and the very wide tenderness diversity accompanying it must be expected in commercial operations that do not use electrical stimulation. PMID- 22055666 TI - Effect of salt on oxidative changes in pre- and post-rigor ground beef. AB - Pre- and post-rigor beef was ground and salt was added to give 0.0, 0.5, 2.0 and 4.0% NaCl (w/w). Samples were removed after 0, 24, 48, 72 and 96 h at 4 degrees C and analyzed for pH, TBA numbers and percentages of reduced myoglobin (Mb), metmyoglobin (MMb) and oxymyoglobin (MbO(2)). After holding for 96 h the samples were cooked in a boiling water bath to an internal temperature of 80 degrees C and held at 4 degrees C for 48 h before TBA analysis. Pre-rigor grinding and salting reduced the post-mortem pH decline and the extent of meat discoloration as shown by the differences in the amount of MMb. The extent of lipid oxidation as measured by TBA numbers was not significantly different for the pre- and post rigor ground salted meat samples, although salt accelerated oxidation during storage. Results demonstrated that pre-rigor grinding and salting of beef produces a more stable bright red color, which appears to be associated with a lower percentage of MMb and a higher ultimate pH in the pre-rigor salted meat. PMID- 22055667 TI - Microbiological and sensory characteristics of pork loin chops: Role of subcutaneous fat. AB - Pork loin chops with the subcutaneous fat attached, without subcutaneous fat and the subcutaneous fat that was removed from chops were packaged and stored at 4 degrees C+/-1 degrees C in polyvinyl chloride (PVC) film for 0-6 days or in high oxygen barrier (HOB) film for 0-28 days. Aerobic plate counts (APCs) of lean and fat of intact chops packaged and stored in either PVC or HOB film did not differ (P>0.05) in most comparisons. The APCs of subcutaneous fat portions that were packaged and stored separately in HOB film often were higher than those of comparable fat samples of intact chops. There was no consistent pattern of differences in the microflora of lean and fat samples. Differences in mean scores for surface discoloration, off odor and overall appearance of intact chops and chops without subcutaneous fat usually were either not significant (P>0.05) or inconsistent. Lean color scores of chops with or without subcutaneous fat did not differ except that chops with the subcutaneous fat removed were rated higher than intact chops during the early periods of storage. Fat color of subcutaneous fat packaged and stored separately in HOB film was often rated higher (slightly whiter) than that of comparable fat of intact chops. PMID- 22055668 TI - The effects of conditioning on meat collagen: Part 2-Direct biochemical evidence for proteolytic damage in insoluble perimysial collagen after conditioning. AB - The effect of proteolytic attack on unwashed and 6 M urea washed bovine perimysial collagen was examined using model systems. Pepsin and cathepsin solubilized collagen continuously over 24h (r = 0.95 andr = 0.88 for time course of pepsin and cathepsin solubilized collagen). Insoluble perimysium treated with pepsin over 24 h resulted in little damage to the insoluble collagenous residue remaining, as evidenced by one-dimensional SDS-polyacrylamide gel electrophoresis. Insoluble perimysium treated with cathepsin resulted in changes to the major peptide bands which were evident after 24 h treatment, visible as broadening and 'fuzziness' of bands, decreased staining intensity, loss of high molecular weight material and a significant reduction in quantity of all peptides when compared with untreated perimysium. The effects of proteolytic action on bovine perimysial collagen in vitro and in conditioned meat were investigated by means of two-dimensional polyacrylamide gel electrophoresis, which provided a more sensitive technique for elucidating changes than the one-dimensional method. The peptide maps obtained from conditioned insoluble perimysium and from insoluble perimysium treated with cathepsin for 24 h were altered relative to the unconditioned insoluble perimysium, with the loss of some peptides and generation of others. The in vitro case was extreme, but was comparable with samples of perimysium from conditioned muscles. The results provide direct biochemical evidence for the presence of proteolytic damage in the insoluble perimysial collagen matrix of meat after conditioning. PMID- 22055669 TI - Fatty acid profiles of the total lipids and lipid oxidation in pork muscles as affected by canola oil in the animal diet and muscle location. AB - Twelve pigs at about 35 days of age were fed a control diet or test diets containing either 10% or 20% canola oil (CO) for 100 days. Four different muscles were excised from each carcass at 24 h post-mortem for analyses. Inclusion of 10% and 20% CO in the animal diet increased (P < 0.05) the relative amount (weight per cent) of unsaturated fatty acids in the total lipids (lipids extracted by 2:1 chloroform-methanol) by 6.7 and 15.8 percentage points, respectively, from 57.8% for the control and also increased (P < 0.05) that of polyunsaturated fatty acids by 5.5 and 9.7 percentage points, respectively, from 19.4% for the control. The 20% CO treatment increased (P < 0.05) the relative amount of monounsaturated fatty acids (primarily C18:1) by 6.1 percentage points from 38.4% for the control, while the 10% CO treatment had no significant effect. The 10% or 20% CO treatment had no significant effect on microsomal enzymic lipid peroxidation activity, heme pigment content, nonheme iron content and total lipid concentration. Overall lipid oxidation in ground muscle samples stored at 4 degrees C tended to be higher for the 10% and 20% CO treatment groups than for the control. The tendency of increased lipid oxidation by the CO treatments apparently resulted from the increased percentages of polyunsaturated fatty acids, rather than from changes in catalytic constituents. PMID- 22055670 TI - Effects of sugars on post-mortem glycolysis in bovine muscle mince. AB - Sternomandibularis muscles from steers were minced, within 75 min of slaughter, with sugars or amylases. The minces were held anoxically at 25 degrees C for at least 7 h. At times samples were removed and chemically analysed. Glucose (1.5%) retarded the post-mortem pH fall, with kinetics similar to those of NaCl (2.0%). Typically, 1.5% glucose maintained the pH at 6.1, whereas control mince attained 5.5. Lesser amounts of glucose had a reduced effect. Other sugars were inactive. The metabolic effects of 1.5% added-glucose were compared with those of an iso osmotic control, 1.5% added-fructose. For the glucose mince there was no change in glucose concentration over 7 h suggesting that the endogenous hexokinase was inactive. Further, more glycogen remained in the glucose mince that in the control, indicating that glucose inhibited glycolysis. This was confirmed by electron microscopy and was reflected in pH and lactate levels. Hexose monophosphates were strongly affected by glucose. In the control, their concentrations each fell in the first 2 h then increased steadily, as expected. In the presence of glucose, their concentrations were initially lower and decreased steadily with time. Concentrations of adenosine phosphates were little affected by glucose, but downstream products of purine metabolism showed marked differences, probably due to enhanced nucleotidase activity above pH 6. Glucose plus yeast hexokinase produced a mince with a rigor pH close to normal. The data indicated that phosphorylase activity was inhibited by glucose, and suggested that glucose was not phosphorylated because of muscle hexokinase inhibitors such as glucose-1,6-diphosphate. PMID- 22055671 TI - A note on the relationships between measures of water holding capacity in the M. longissimus dorsi and total drip loss from butchered pig carcasses during storage. AB - Twenty pig carcasses were selected to represent a range of meat quality. The water holding capacity (WHC) of the M. longissimus dorsi (LD) was estimated using several methods and the usefulness of these measures examined to predict the overall loss in weight from the butchered carcasses when jointed and displayed in a manner corresponding to a retail situation. There was a linear relationship between the logarithms of percentage loss in weight of the butchered carcass and days of display time. The total weight loss from the butchered carcasses after 5 days ranged from 2.2 to 6.4% and the best relationship with this weight loss was for WHC assessed by loss of exudate from slices of LD suspended in netting bags for 72 h at 1 degrees C (r = 0.88, P < 0.001). Measures of WHC based on high or low speed centrifugation, or a filter paper press method, gave slightly poorer correlations. However, all WHC methods except low speed centrifugations gave correlations which were better than those with pH measured at 45 min post mortem, or reflectance or Fibre Optic Probe Values at 24 h post mortem. PMID- 22055672 TI - Editor's Note. Bringing Gender Home: Implementing Gender-Responsive HIV/AIDS Programming for U.S. Women And Girls. PMID- 22055673 TI - Recommendations from "Bringing Gender Home: Implementing Gender-Responsive HIV/AIDS Programming for U.S. Women and Girls". PMID- 22055674 TI - Gender, race + geography = jeopardy: marginalized women, human rights and HIV in the United States. AB - Across the United States, laws, policies, and practices put women living with HIV in jeopardy. In particular, the dignity, health, and well-being of women living with and at risk for HIV as well as the health and well-being of their families and communities is hampered by punitive laws and policies. Laws and policies that do not meet, or worse, criminalize women's sexual and reproductive rights result in the economic, social and political deprivation of marginalized women and girls and especially those living with and at risk of HIV. These laws and policies exacerbate an already outsized HIV epidemic in underserved communities, and communities of color in the United States. This article draws from and builds on a human rights workshop that took place as part of the forum "Bringing Gender Home: Implementing Gender Responsive HIV/AIDS Programming for US Women and Girls," sponsored by the Office of Women's Health. It focuses on the damaging impact of laws, policies, and practices that criminalize women's sexuality. These laws significantly impact the well-being of women living with and at risk for HIV, and have an impact on the capacity of poor women of color in the United States to fully exercise their rights. When laws that purport to protect public health have the result of limiting women's reproductive choices, or have a disproportionate impact on marginalized groups such as sex workers, fundamental breaches of women's rights occur. PMID- 22055675 TI - Sexual and reproductive health and rights: integration as a holistic and rights based response to HIV/AIDS. AB - For decades, donors, governments, and civil society have recognized the importance of sexual and reproductive health and rights (SRHR) in efforts to alleviate poverty and advance gender equality and women's rights. More recently, in the battle against HIV/AIDS--and given the unique challenges the pandemic presents for health and development--the global community has acknowledged the benefits of synergizing sexual and reproductive health and HIV/AIDS interventions. However, the United States has been slow to incorporate lessons learned from the international experience when it comes to integrating HIV/AIDS, SRHR, and gender equality in the fight against HIV/AIDS. This article highlights the importance of SRHR and lessons learned from SRHR-HIV integration to inform U.S. domestic and global AIDS strategies and interventions. PMID- 22055676 TI - Violence prevention among HIV-positive women with histories of violence: healing women in their communities. AB - Experiences of past and current gender-based violence are common among HIV positive women in the United States, who are predominantly from ethnic minority groups. However, culturally congruent, feasible interventions for HIV-positive women who have experienced past and/or current violence are not widely available. The Office on Women's Health Gender Forum has made several recommendations for responding to the National HIV/AIDS Strategy Implementation Plan, including recommendations to incorporate gender-based violence prevention into a comprehensive, gender-responsive national strategy. This paper draws on an example of a community-based project for HIV-positive women, the Healing Our Women Project, to illustrate how violence prevention can be achieved within peer led and community-based programming. Strong community partnerships, responsiveness to community needs and local cultural norms, a trained workforce, and culturally competent care are programmatic cornerstones of gender-responsive services. HIV-positive women with histories of gender-based violence and risk factors for current and future violence deserve the highest quality gender responsive services to ensure that they can address their health needs within contexts of safety and respect. PMID- 22055677 TI - Keeping our hearts from touching the ground: HIV/AIDS in American Indian and Alaska Native women. AB - HIV/AIDS is a critical and growing challenge to American Indian and Alaska Native (AIAN) women's health. Conceptually guided by the Indigenist Stress-Coping Model, this paper explores the historical and contemporary factors implicated in the HIV epidemic among AIAN women and the co-occurring epidemics of sexual violence and substance abuse. The authors also outline multiple indicators of resiliency in AIAN communities and stress the need for HIV prevention interventions for AIAN women to capitalize on cultural and community strengths. PMID- 22055678 TI - Priority issues concerning HIV infection among women. AB - During the last decade, the enormous impact the global HIV epidemic was having on women's health was fully recognized. However, this recognition has not wholly extended to the domestic setting; in much of the United States, the dominant focus remains on HIV infection among men who have sex with men. The relatively low prevalence of HIV infection among U.S. women (a huge population group) versus men who have sex with men and injection drug users (much smaller groups) contributes to the perception that HIV is not a major domestic women's health consideration. PMID- 22055679 TI - HIV/AIDS programming in the United States: considerations affecting transgender women and girls. AB - To be truly gender responsive, HIV/AIDS programming for women and girls also needs to be fully gender inclusive. Gender identity is not necessarily determined by one's sex assigned at birth and not everyone is only or always simply "male" or "female." Transgender women (transwomen) and girls are those individuals whose gender identity and/or expression do not align with the "male" sex they were assigned at birth. This definition is inclusive of a diverse population whose identities, language, communities, and behaviors may vary widely. However, based on recent increases in public health literature that aims to elucidate the social context that puts transwomen and girls at risk for adverse health outcomes, we offer some formative considerations for the implementation of gender-responsive and gender-inclusive HIV/AIDS programming in the United States. PMID- 22055680 TI - Preventing HIV in U.S. women and girls: a call for social action. AB - Successes in HIV prevention efforts in the U.S. have resulted in drastic reductions in the number of new infections in the U.S. among white gay men and injection drug users, a stabilization in overall annual rates of new HIV infections, and near eradication of mother-to child transmission of HIV. Despite this remarkable progress, the proportion of AIDS cases in women has slowly, quietly, and steadily increased from 7% in 1985 to 25% in 2008. The fact the prevention efforts have not reduced HIV spread among women suggests that targeting the individual behaviors of women to prevent HIV acquisition is not a sufficiently effective public health strategy. Interventions that more broadly address the needs of women and their families, and address the contextual factors in which HIV risk occurs are more likely to lead to measurable and sustainable progress. Over the past 30 years, we have seen the U.S. HIV epidemic in women become similar to patterns of HIV risk among women in the developing world. In 2009, 85% of women who acquired HIV became infected through sex with a man and the majority (83%) of them were non-white women. Efforts to understand these immense disparities and create gender-responsive strategies must be a priority within our National HIV/AIDS Strategy. PMID- 22055681 TI - Functional nanoscale organization of signaling molecules downstream of the T cell antigen receptor. AB - Receptor-regulated cellular signaling often is mediated by formation of transient, heterogeneous protein complexes of undefined structure. We used single and two-color photoactivated localization microscopy to study complexes downstream of the T cell antigen receptor (TCR) in single-molecule detail at the plasma membrane of intact T cells. The kinase ZAP-70 distributed completely with the TCRzeta chain and both partially mixed with the adaptor LAT in activated cells, thus showing localized activation of LAT by TCR-coupled ZAP-70. In resting and activated cells, LAT primarily resided in nanoscale clusters as small as dimers whose formation depended on protein-protein and protein-lipid interactions. Surprisingly, the adaptor SLP-76 localized to the periphery of LAT clusters. This nanoscale structure depended on polymerized actin and its disruption affected TCR-dependent cell function. These results extend our understanding of the mechanism of T cell activation and the formation and organization of TCR-mediated signaling complexes, findings also relevant to other receptor systems. PMID- 22055682 TI - 18F-FDG uptake on PET in primary mediastinal non-thymic neoplasm: a clinicopathological study. AB - BACKGROUND: The usefulness of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET) has been investigated in thymic epithelial tumors. However, little is known about PET imaging of (18)F-FDG in primary non thymic mediastinal neoplasms. The aim of this study is to explore the clinicopathological significance of (18)F-FDG PET in primary mediastinal (non thymic) neoplasms. METHODS: Twenty-one patients with mediastinal neoplasms who underwent (18)F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (Glut1); glucose transporter 3 (Glut3); hypoxia-inducible factor-1 alpha (HIF-1alpha); hexokinase I; vascular endothelial growth factor (VEGF); microvessels (CD34); epidermal growth factor receptor (EGFR); Akt/mTOR signaling pathway (p-Akt and p mTOR); cell cycle control (p53). RESULTS: Seventeen of 21 patients were imaged on PET system using (18)F-FDG, but 4 patients with a histology of cyst showed nothing abnormal in PET scans. The histology of the resected tumors was as follows: 6 schwannoma, 3 teratoma, 4 cyst, 3 sarcoma, 1 undifferentiated carcinoma, 1 seminoma, 1 mediastinal goiter, 1 ganglioneuroma, and 1 Hodgkin lymphoma. (18)F-FDG uptake was significantly correlated with Glut1, HIF-1alpha, EGFR, p-Akt and p-S6K. These biomarkers were highly expressed in schwannoma, teratoma and high grade malignancies, whereas all patients with cyst and ganglioneuroma had no positive expression of these biomarkers. High uptake of (18)F-FDG was significant associated with Glut1, VEGF, EGFR, p-Akt, p-S6K and tumor maximal size. CONCLUSION: The amount of (18)F-FDG uptake in primary mediastinal non-thymic neoplasms is determined by the presence of glucose metabolism (Glut1), hypoxia (HIF-1alpha) and upstream components of HIF-1alpha (EGFR, p-Akt and p-S6K). PMID- 22055683 TI - Three-dimensional volume rendering digital subtraction angiography in comparison with two-dimensional digital subtraction angiography and rotational angiography for detecting aneurysms and their morphological properties in patients with subarachnoid hemorrhage. AB - OBJECTIVE: Subarachnoid hemorrhage (SAH), which can cause mortality and severe morbidity, is a serious condition whose underlying cause must be determined. We aimed to compare 2D digital subtraction angiography (2DDSA), rotational angiography (RA) and 3D volume rendering digital subtraction angiography (3DVRDSA) for detecting aneurysms and their morphological properties in patients with subarachnoid hemorrhage. MATERIALS AND METHODS: After an initial diagnosis of SAH with computed tomography, 122 patients (52 males and 70 females with a mean age of 47.77 +/- 12.81 ranging between 20 and 83 years) underwent 2DDSA imaging, RA and 3DVRDSA imaging for detection of aneurysms. The location of the aneurysm, the best working angles, the dome/neck ratios, the largest diameter of the aneurysm, the shape of the aneurysm, the presence of spasms or pseudostenoses, and the relationship to the neighboring arteries were recorded. RESULTS: 2DDSA missed 15.6% of the aneurysms that had a mean size of 2.79 +/- 0.74 mm. RA was superior to 2DDSA for detecting aneurysm neck, and 3DVRDSA was superior to RA for detecting aneurysm neck. 3DVRDSA conclusively depicted the shape of the aneurysms in all patients. 3DVRDSA imaging was superior to 2DDSA and RA in the detection of the aneurysm relationship to neighboring arteries. The sensitivity and specificity of 3DVRDSA imaging for the detection of vasospasms were 100 and 84%, respectively. CONCLUSIONS: 3DVRDSA imaging is superior to 2DDSA and RA for detecting intracranial aneurysms and their morphological properties, especially those of small, ruptured aneurysms. However, 2DDSA should not be neglected in cases of vasospasm. PMID- 22055684 TI - Perfusion measurement of the whole upper abdomen of patients with and without liver diseases: initial experience with 320-detector row CT. AB - OBJECTIVES: To report initial experience of upper abdominal perfusion measurement with 320-detector row CT (CTP) for assessment of liver diseases and therapeutic effects. MATERIALS AND METHODS: Thirty-eight patients who were suspected of having a liver disease underwent CTP. There were two patients with liver metastases, two with hemangiomas, and four with cirrhosis (disease group). CTP was repeated for four patients with cirrhosis or hepatocellular carcinoma (HCC) after therapy. Hepatic arterial and portal perfusion (HAP and HPP) and arterial perfusion fraction (APF), and arterial perfusion (AP) of pancreas, spleen, stomach, and intra-portal HCC were calculated. For disease-free patients (normal group), the values were compared among liver segments and among pancreatic and gastric parts. The values were compared between groups and before and after therapy. RESULTS: No significant differences were found in the normal group except between APFs for liver segments 3 and 5, and fundus and antrum. Mean HAP and APF for the disease group were significantly higher than for the normal group. APF increased after partial splenic embolization or creation of a transjugular intrahepatic portosystemic shunt. HPP increased and AP of intra portal HCC decreased after successful radiotherapy. CONCLUSIONS: 320-Detector row CT makes it possible to conduct perfusion measurements of the whole upper abdomen. Our preliminary results suggested that estimated perfusion values have the potential to be used for evaluation of hepatic diseases and therapeutic effects. PMID- 22055685 TI - Congenital renal anomalies in patients with classic bladder exstrophy. AB - OBJECTIVE: To determine the proportion and type of renal anomalies that occur in children born with classic bladder exstrophy. MATERIAL AND METHODS: All patients in a database of 1044 patients with the bladder exstrophy-epispadias-cloacal exstrophy complex were reviewed. Those with classic bladder exstrophy had their complete medical records reviewed and children with radiographic evidence of congenital renal anomalies were identified and characterized. RESULTS: A total of 674 patients were identified with classic bladder exstrophy, of whom 462 had renal ultrasounds at the authors' institution. In this population, 13/462 (2.8%) had concomitant renal anomalies. The most common malformation was a duplicated collecting system in 6 patients. Hypoplastic or absent kidneys were present in 3 patients, pelvic kidney in 2, ureteropelvic junction obstruction in 1, and multicystic dysplastic kidney in 1 patient. CONCLUSION: Isolated renal anomalies occur at a rate of 2.8% in children born with classic bladder exstrophy. Although uncommon in this rare birth defect, anatomic understanding of the entire genitourinary system is critical for operative planning and long-term follow-up of patients with bladder exstrophy. PMID- 22055686 TI - A more "conventional" way to perform percutaneous endopyeloplasty: a feasibility study. AB - OBJECTIVE: Percutaneous endopyeloplasty is a horizontal suturing of the endopyelotomy incision via a unique percutaneous tract. We present a feasibility study of our technique of percutaneous endopyeloplasty using a conventional suture with a laparoscopic needle holder via the nephroscope. MATERIALS AND METHODS: A longitudinal endopyelotomy incision is performed through a 24-Fr working sheath placed via an upper calyx. Then an initial suture is placed, approximating the endopyelotomy incision distal and proximal apex, using a conventional absorbable 13-mm needle suture with a lengthened 3.5-mm pediatric laparoscopic needle holder, via the nephroscope. If possible, an additional 2 sutures are eventually placed, 1 on either side of the initial midline suture. RESULTS: Percutaneous endopyeloplasty, using a conventional suture with a pediatric laparoscopic needle holder via a nephroscope, is technically possible, reproducible, and effective, and was performed in 10 consecutive patients. The tissue approximation provides a fast, full thickness ureteral healing. Endopyelotomy horizontal suturing leads to a wider caliber reconstruction of the ureteropelvic junction. CONCLUSION: Percutaneous endopyeloplasty is a promising technique. Our procedure for endopyeloplasty is technically feasible and effective, with little need for highly specialized equipment. However, further technical experience and longer follow-up in a larger group of patients are necessary for more development of this technique. PMID- 22055687 TI - SIU Scholar: Dr. Ahmed Muhammed. PMID- 22055688 TI - Simultaneous laparoendoscopic single-site radical nephrectomy for native kidney and open nonischemic partial nephrectomy to treat concomitant renal cell carcinomas in native and transplant kidneys and to preserve allograft function. AB - OBJECTIVE: To report a technique of minimally invasive radical nephrectomy for a native renal cell carcinoma (RCC) and nonischemic open partial nephrectomy for a transplant kidney RCC with only a laparoendoscopic single-site (LESS) incision. Concomitant RCCs in a native and transplant kidneys are very rare. Conventional surgical approach requires a long incision. METHODS: A 50-year-old man 14 years after renal transplant was found incidentally to have concomitant RCCs in his native right kidney and transplant kidney. A right lower abdomen Gibson incision, along his transplant wound, was used initially for LESS right radical nephrectomy and lymphadenectomy, and that same wound was used for a nonischemic open partial nephrectomy in the transplant kidney. RESULTS: The LESS right radical nephrectomy took 3.25 hours with estimated blood loss (EBL) of 80 mL and the partial nephrectomy for the transplant kidney took 3 hours with EBL of 220 mL. No transfusion was required. Pathologic examination revealed both tumors to be RCC, clear cell type, and 6.5 cm in the right native kidney and 2.8 cm in the transplant kidney. The final wound measured 9 cm. Postoperative recovery was uneventful with inpatient narcotic requirement of 37 mg morphine sulfate equivalent, and oral intake of food resumed in 2.5 days. His allograft function was well preserved with a serum creatinine unchanged (1.4 mg/dL) at discharge. CONCLUSION: In a patient with concomitant tumors in a native kidney and a transplant kidney, this unique approach provides exceptional benefits of minimally invasive tumor excision for both tumors, and good preservation of renal function. PMID- 22055689 TI - Risk factors for progressive deterioration of semen quality in patients with varicocele. AB - OBJECTIVE: To assess the risk factors for progressive deterioration of semen quality (PDSQ) in adult patients with varicocele. METHODS: A total of 32 men with left varicocele and impaired semen quality (group 1) and 30 age-matched patients with left varicocele and normal semen quality (group 2) were recruited for the present study. All the subjects received conservative treatment, and the parameters for evaluation every 12 months included semen quality, peak retrograde flow (PRF) and spontaneous venous reflux by color Doppler ultrasonography, body mass index, serum concentration of follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, testicular volume and discrepancy, grade of varicocele, and scrotal temperature. RESULTS: The mean follow-up time was 63.2 months (range 60-66). The patients in group 1 had a significantly greater PRF, lower testicular volume, greater testicular volume discrepancy, lower testosterone level, higher scrotal temperature, and greater follicle-stimulating hormone level than those in group 2 at first. The semen quality deteriorated in 28 subjects (87.5%) in group 1, but in only 6 patients (20%) in group 2 during follow-up. Furthermore, the 6 subjects with PDSQ in group 2 had greater PRF and scrotal temperature than those without. CONCLUSION: The rate of PDSQ was significantly greater in the varicocele patients with an initially abnormal semen quality than in those with initially normal semen quality (87.5% vs 20%). Furthermore, the varicocele patients with initially normal semen quality who had greater PRF and scrotal temperature might have a greater risk of PDSQ. PMID- 22055690 TI - Interactions between cholinergic and prostaglandin signaling elements in the urothelium: role for muscarinic type 2 receptors. AB - OBJECTIVE: To characterize the interactions between the cholinergic and prostaglandin signaling systems within the urothelium-lamina propria of the guinea pig and elucidate the role of muscarinic receptors in these interactions. METHODS: The urothelium-lamina propria was isolated from guinea pig bladders, cut into strips (5*10 mm), and maintained in vitro. The tissue was either stretched or left unstretched but exposed to 2'(3')-O-(4-benzoylbenzoyl)adenosine-5' triphosphate tri(triethylammonium) salt, arecaidine, and prostaglandin E2 (PGE2). Acetylcholine and PGE2 release was measured using a GeneBLAzer M3 CHO-K1-bla cell reporter assay and an enzyme immunoassay, respectively. The role of the muscarinic type 2 and 3 (M2 and M3, respectively) receptors and nitric oxide in mediating PGE2 release was determined in the presence of the muscarinic antagonists 11-[(2-[(diethylamino)methyl]-1-piperidinyl)acetyl]-5,11-dihydro-6H pyrido[2,3b][1,4] benzodiazepin-6-one and darafenicin and a nitric oxide donor (NONOate). RESULTS: Acetylcholine release was detected in response to stretch and in the unstretched preparations exposed to PGE2 or the adenosine triphosphate analog 2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate tri(triethylammonium) salt. The cholinergic agonist arecaidine induced a concentration-dependent production of PGE2 (half-maximal concentration 75 nM). The arecaidine stimulation of PGE2 production was inhibited in a dose-dependent manner by the antagonist AFDX-116 (M2>M3; half-maximal inhibition 110 nM) but not darifenacin (M3>>M2). Finally, in the presence of the nitric oxide donor, NONOate, arecaidine stimulated PGE2 production was inhibited. CONCLUSION: These observations demonstrate that complex signal interactions occur within the urothelium involving acetylcholine, adenosine triphosphate, nitric oxide, and PGE2. In addition, the data have demonstrated a role for muscarinic M2 receptors and nitric oxide in the cholinergic regulation of PGE2 production in the bladder wall. PMID- 22055691 TI - Prostate sampling by 12-core biopsy: comparison of the biopsy results with tumor location in prostatectomy specimens. AB - OBJECTIVE: To analyze the diagnostic performance of individual prostate biopsy cores. The 12-core transrectal prostate biopsy scheme has emerged as a standard of care. However, quality of sampling may vary in different areas of the prostate included in this procedure. MATERIAL AND METHODS: Two-hundred fifty men underwent radical prostatectomy at our institution. All participants had a systematic 12 core transrectal prostate biopsy containing lateral and medial cores from each side of the apical, medial and basal thirds of the prostate. Biopsy results were matched with histologic maps of the prostatectomy specimens. Sensitivity, negative predictive value (NPV), and overall accuracy were calculated for each biopsy core location and compared between different groups of cores. In addition, patients in the upper quartile of prostate weight were compared with the rest of the cohort. RESULTS: Sensitivity, NPV, and overall accuracy were significantly lower for apical cores. Average NPV and overall accuracy of basal and mid-lateral biopsies were inferior to those of medial biopsies on the same levels. However, sensitivity of these lateral cores was similar to that of the medial cores. Sensitivities of apical and mid cores were significantly lower in patients with larger prostates. CONCLUSION: Decreased accuracy in lateral mid- and basal cores results from higher frequencies of cancer in corresponding prostate areas, and therefore additional samples should be taken at these locations. In addition, diagnostic accuracy of apical cores may be improved through better targeting of the prostatic apex. This may be particularly important in patients with larger prostates. PMID- 22055692 TI - Racial differences in the prevalence of overactive bladder in the United States from the epidemiology of LUTS (EpiLUTS) study. AB - OBJECTIVES: To estimate the prevalence of overactive bladder (OAB) in men and women in the United States (US) to determine whether there were racial differences. METHODS: This was a secondary analysis of data from the EpiLUTS (Epidemiology of Lower Urinary Tract Symptoms) survey, an Internet-based cross sectional, population-representative epidemiologic survey conducted in the US, UK, and Sweden. These analyses were limited to the data of men and women aged 40 and older from the US. The presence of OAB was defined as experiencing urinary urgency or urinary urgency incontinence. Case definitions of OAB symptoms were categorized as occurring at least "sometimes." Prevalence rates of OAB were estimated by race. Logistic regression analyses were conducted for each gender to examine the role of race on OAB status, controlling for risk factors and comorbid conditions. RESULTS: The response rate in the US was 59.6%. A total of 9237 men and 10,407 women self-identified their race and were included in the analytic sample. The prevalence of OAB at least "sometimes" ranged from 26% in Asian men to 33% in African American men. Similarly, the prevalence of OAB at least "sometimes" was lowest in Asian women (27%) and highest in African American women (46%). Race was predictive of OAB in men but not for women. CONCLUSIONS: The prevalence of OAB ranged from 26-33% across races for men and from 27-46% across races for women. African American and Hispanic race is predictive of OAB for men but not for women. PMID- 22055693 TI - Utility of urothelial mRNA markers in blood for staging and monitoring bladder cancer. AB - OBJECTIVE: To test the efficiency of 6 mRNA bladder markers in staging urothelial cell carcinoma (UCC) and monitoring UCC dissemination from blood samples. METHODS: From 2002 to 2009, 347 blood samples were collected from 150 patients with UCC and 29 healthy controls. Sequential blood sampling was performed in patients undergoing cystectomy at surgery and 6, 12, 18, and 24 months postoperatively. The median follow-up was 33 months. The presence of KRT20, FXYD3, C10orf116, UPK2, AGR2, and KRT19 markers in blood was evaluated in all patients and controls by measuring the gene expression using preamplified cDNA and reverse transcriptase quantitative polymerase chain reaction. Gene expression data were correlated with the tumor risk, follow-up, and outcomes data. RESULTS: Expression of C10orf116 and KRT19 genes differed between patients and controls (P<.001). KRT20, C10orf116, and AGR2 differentiated between low- and high-risk nonmuscle-invasive bladder cancer (P=.001, P=.011, and P=.001, respectively). FXYD3 differentiated between patients with high-risk nonmuscle-invasive bladder cancer and those with muscle-invasive bladder cancer (P=.009). In contrast, the 6 markers showed no differences in gene expression between metastatic and patients without metastases who had not undergone cystectomy (P=NS). None of the markers were significantly increased in the metastatic patients at 6, 12, 18, or 24 months after surgery. CONCLUSION: The gene expression of bladder-specific mRNA markers in blood was different among the various tumor risk groups of patients with UCC. However, this gene expression analysis is not suitable for predicting metastases or monitoring UCC hematogenous dissemination in patients who have undergone cystectomy. PMID- 22055694 TI - Silent ureteral stones: impact on kidney function--can treatment of silent ureteral stones preserve kidney function? AB - OBJECTIVE: To report our experience with silent ureteral stones and expose their true influence on renal function. METHODS: We analyzed 506 patients who had undergone ureterolithotripsy from January 2005 to May 2010. Silent ureteral stones were calculi found in the absence of any specific or subjective ureteral stone-related symptoms. Of the 506 patients, 27 (5.3%) met these criteria (global cohort). All patients were assessed postoperatively with dimercaptosuccinic acid scintigraphy (DMSA). A difference in relative kidney function of >10% was considered abnormal. Pre- and postoperative comparative DMSA analyses were electively obtained for 9 patients (kidney function cohort). A t test was used to assess the numeric variables, and the chi-square test or Fisher's exact test was used for categorical variables. Two-tailed P<.05 was considered statistically significant. RESULTS: Stones were diagnosed by radiologic abdominal evaluation for nonurologic diseases in 40% and after previous nephrolithiasis treatment in 33%. The primary therapy was ureterolithotripsy in 88%. The mean follow-up time was 23 months. The overall ureteral stone-free rate after 1 and 2 procedures was 96% and 100%, respectively. In the global cohort, the mean pre- and postoperative serum creatinine levels were similar (P=.39), and the mean postoperative function on DMSA was 31%. In the kidney function cohort, no difference was found between the pre- and postoperative DMSA findings (22%+/-12.1% vs 20%+/-11.8%; P=.83) and serum creatinine (0.8+/-0.13 mg/dL vs 1.0+/-0.21 mg/dL; P=.45). CONCLUSION: Silent ureteral stones are associated with decreased kidney function present at the diagnosis. Hydronephrosis tends to diminish after stone removal, and kidney function remains unaltered. PMID- 22055695 TI - Clinical outcomes of intracavernosal injection in postprostatectomy patients: a single-center experience. AB - OBJECTIVE: To evaluate the clinical outcomes of intracavernosal injection (ICI) use in an undifferentiated group of men with erectile dysfunction at various stages after radical prostatectomy. METHODS: Retrospective charts, mailed questionnaires, and a telephone survey of patients after radical prostatectomy prescribed ICI by a single urologist from January 2006 to January 2008. The patient demographics and prostate cancer profiles, current ICI use patterns, adverse outcome, and clinical efficacy were collected. RESULTS: A total of 117 patients completed the questionnaire. The mean age was 65+/-6.2 years, and the patients had undergone radical prostatectomy 4.1+/-2.7 years earlier. Most patients had hypertension (38%) and dyslipidemia (26%); 51% of the patients actively used ICI, with a median of 3 attempts monthly. Sixty-eight percent of all patients were sexually active (98% of ICI users vs 36% of ICI nonusers, P<.001). In the sexually active patients, ICI was associated with significantly greater International Index of Erectile Function scores (20.8+/-4.1 vs 16.0+/ 6.9, P=.008). ICI was most frequently discontinued because of patient-perceived ineffectiveness (48%), pain (21%), and prolonged erections (11%). Twenty-eight percent of patients had erections lasting longer than they had wished at some point in their treatment, with 10% incidence of priapism. CONCLUSION: ICI use among patients after prostatectomy can be highly effective but has a significant attrition rate (49%). The identification of reasons for discontinued use can aid healthcare providers to support patients in the early period after adoption of ICI and to direct their counseling more effectively. PMID- 22055696 TI - Impact of radiological technologists on the outcome of shock wave lithotripsy. AB - OBJECTIVE: To evaluate the correlation of radiological technologists (RTs) and the outcome of shock wave lithotripsy (SWL) in terms of fluoroscopy time, fragmentation rate, and stone-free rate. MATERIAL AND METHODS: A retrospective review of a prospectively collected database of 601 SWL treatments between June 2009 and March 2010 was performed. Patients with radiolucent stones were excluded. SWL was done by 6 RTs with different levels of experience. Follow up was available for 534 treatments. Multivariate analysis was performed. RESULTS: RTs (A-F) performed 144, 109, 118, 58, 57, and 48 SWL sessions, respectively. There was no statistical difference among RTs in terms of mean stone size or stone location. Compared with other RTs, RT A had a significantly lower mean fluoroscopy time of 129 seconds (95% CI 120.8-137.3) (P <.001), higher stone-free rate (75.7%; P = .035), and stone fragmentation rate after a single SWL session (82.6%; P = .004). After correcting for stone size and location, fluoroscopy time (P <.001), fragmentation rate (P = .002), and stone-free rate (P = .04) maintained their significance. When comparing the top 3 RTs performing >100 SWL sessions, RTs B and C had significantly higher fluoroscopy time compared with RT A (OR [95% CI] 1.84 [1.38-2.45]; P <.001 and 2.67 [2.00-3.57]; P <.001), respectively. After correcting for stone size and location, RT B had significantly lower fragmentation rate when compared with RT A (OR [95% CI] 0.21 [0.05-0.86], P = .03]. However, there were no significant differences among the top 3 RTs in terms of stone-free rates. CONCLUSION: RTs significantly differ in fluoroscopy usage in addition to stone fragmentation and stone-free rates. PMID- 22055698 TI - Efficiency of protein extraction and recovery from meat industry by-products. AB - Data concerning the efficiency of protein extraction from meat waste tissues are presented. The tissues investigated were the lungs, stomach and small and large intestines of the ox, sheep and pig. Practically all of the protein, with the exception of connective tissue proteins, was solubilised under optimum extraction conditions both with alkali and anionic detergent. The disadvantages of isoelectric precipitation of alkaline extracted proteins have been investigated in detail using polyacrylamide gel electrophoresis incorporating sodium dodecyl sulphate (SDS). The compositions of the protein isolates from the various tissues studied differed from those of the soluble extracts and supernatants or wheys. However, a component of MW 75,000 daltons was characteristic of the wheys from each tissue. The compositions of both isolates and wheys are discussed in the light of structural and cytoplasmic proteins present in smooth muscle tissues. The usefulness of anionic polysaccharides as a means of whey protein recovery is discussed, together with similar benefits achieved using SDS. PMID- 22055697 TI - Neuroaxonal dystrophy in Australian Merino lambs. AB - Neuroaxonal dystrophy (NAD) is a morphological abnormality in man and animals that is characterized by the occurrence of numerous axonal swellings (spheroids) in the nervous system. NAD has been described in Suffolk lambs in the USA, Merino lambs in Australia and several breeds of sheep in New Zealand. This paper describes the clinicopathological changes of only the second occurrence of NAD reported in Merino lambs. There were some features (myelin loss, gliosis and visual impairment) in these Australian cases that have not been reported previously in ovine NAD. Application of immunohistochemical markers of axonal transport suggested that disruption of this transport mechanism contributed to spheroid development. PMID- 22055699 TI - The influence of temperature on some parameters for dry sausage during ripening. AB - There are several processing parameters which are important for the production of good quality dry sausage. One of these is ripening temperature. In this study ripening temperatures of 15, 20, 25 and 30 degrees C for zervelat sausage in 60 mm calibre casings, and using starter culture, were compared by measurement of pH, firmness, water activity, water content and weight loss during a 28-day period. The results of the study showed that temperature of ripening directly influences the rate of development of firmness and pH fall in the dry sausage. The velocity of ripening increased with ripening temperature so that a 5 Celsius degree increase in temperature approximately doubled the rate. The firmness increased as the pH dropped below 5.4. Water activity decreased continuously, the rate increasing as the ripening temperature was increased. Water content behaved similarly. At the lowest ripening temperature (15 degrees C) the pH did not drop below 5.2. Higher ripening temperatures resulted in a slightly higher ultimate firmness of the dry sausage. PMID- 22055700 TI - Use of a conditioned stimulus to study whether the initiation of electrical pre slaughter stunning is painful. AB - In an attempt to determine whether electrical pre-slaughter stunning is painful, sheep were conditioned to expect stunning by exposure to a light for 5 sec before the current was applied. Sheep in five groups received 90 V, 50 Hz, for 3, 6, 9, 12 and 15 sec, respectively. The heart rate, packed cell volume (PCV) and plasma glucose levels were used to assess the physiological response of the sheep to electrical stunning. After daily exposure to this regime for eleven days, the light stimulus was applied, but was not followed by stunning. The heart rate was not affected by the light. Both PCV and plasma glucose levels showed marked increases when stunning followed exposure to the light. Neither value rose on the twelfth day, when exposure to the light was not followed by stunning. It is concluded that the initiation of electrical stunning was not a painful experience to the sheep in this experiment. No attempt was made to assess the depth or duration of insensibility following stunning. PMID- 22055701 TI - Review of the flavour-contributing volatiles and water-soluble non-volatiles in pork meat and derived products. AB - In relation to the problem of meat flavour, volatile and minor non-volatile components of raw, cooked and pre-cured cooked pork meat (carbonyls, sulphur compounds, volatile fatty acids, alcohols and other volatiles, nucleotides and their decomposition products, free fatty acids) are considered. Quantitative changes in some of the components, as effected by technological treatments such as heating, curing and curing and heating, are compared. The possibility of evaluating the quality of heated cured pork products by the hydrogen sulphide/mercaptan ratio is indicated. PMID- 22055702 TI - Early-postmortem cooling rate and beef tenderness. AB - Four distinct early-postmortem cooling rates (as measured within the longissimus muscle) were obtained by exposing one side of each of five fat and five lean steers to moving air at -2 degrees and the other to 9 degrees static air. Loin steaks of the fastest cooling group were found to be the least tender and to have the shortest sarcomeres; the three remaining groups differed significantly from each other in tenderness but not in sarcomere length. For all twenty sides, regardless of treatment group, tenderness was highly dependent on, and almost linearly related to, the muscle temperature attained at 2 hours post mortem (27 40 degrees ), the relationship deteriorating rapidly as longer time intervals and lower temperature ranges were considered. The results indicate that (1) except in very rapidly chilled lean carcasses, cold shortening is not a significant determinant of tenderness; (2) the enhanced tenderness of slowly chilled beef is not due primarily to the relatively prolonged avoidance of shortening-inducive temperatures but to the accompanying retardation of cooling during the first 2-4 hours post mortem, when muscle temperatures are still far above those associated with cold shortening and (3) the generally recognised superior tenderness of well finished beef is largely (and perhaps entirely) a consequence of slower cooling during this very early-postmortem period. PMID- 22055704 TI - Erratum. PMID- 22055703 TI - Developments in meat science-1 Edited by R. A. Lawrie, Applied Science Publishers Ltd, London. xii + 245 pp. 1980, Price: L17.00. PMID- 22055705 TI - Effects of normal, light/normal or double stunning on the incidence and severity of blood splash in lambs. AB - One-hundred-and-twenty lambs were divided into three equal groups which were subjected to head electrical anaesthesia before bleeding. The normal group was stunned and bleeding was initiated within 5 to 8 s. The light/normal group was partially stunned and then treated as the normal group after a delay of 10s. The double stunned group was electrically anaesthetised, allowed to recover and then restunned and bleeding was initiated within 5 to 8 s. The light/normal and double stunning procedures increased the incidence and severity of carcass blood splash compared with normal stunning but the increase was less than that sometimes seen in normal mobs of head-stunned sheep and which occurs for unknown reasons. PMID- 22055706 TI - Tissue growth patterns in the carcasses of water buffalo and friesian crossbred cattle: Part 2-individual bones and anatomical bone groups. AB - Twelve Egyptian buffalo, nine ? Friesian * ? Egyptian native Baladi (half Friesian) and nine ? Friesian * ? half Friesian (three-quarter Friesian) bulls were serially slaughtered between 161 and 560 kg for buffaloes and between 176 and 448 kg for cattle. Anatomical dissection data from the left sides of the carcasses were used to examine the growth of individual bones and bone groups. No significant genetic differences with respect to the growth patterns of bones relative to total side bone were reported, indicating that bones followed similar patterns in buffaloes and cattle. Differential growth of bones occurred following an increase of impetus from cervical vertebrae to os sacrum and with growth coefficients for bones of the forelimb correspondingly higher than for the hindlimb and the entire axial and appendicular skeletons following, respectively, late- and early-maturing patterns. Some significant, though minor, differences between buffaloes and cattle were found when weights of individual bones were adjusted to constant side bone weight. As compared with Friesian crosses, buffaloes had more weight of the ribs and less weight of the vertebral column in the axial skeleton, and more weight of radius-and-ulna and less weight of scapula in the forelimb at equal total bone. There were no significant differences between buffaloes and Friesian crossbreds in the proportion of total bone occurring in the entire hindlimbs and forelimbs and in the distribution of total bone between axial and appendicular skeletons. PMID- 22055707 TI - Moisture mobility in meat emulsion during thermal processing: Analysis of slab moisture profile. AB - A determination of the moisture distribution in meat emulsion slab at several process times as a function of its composition and temperature, and smokehouse relative humidity, with a technique and model for determining the corresponding moisture mobility are presented. The moisture diffusivity was increasing with the decrease in the fat-protein ratio and increase in the product temperature and moisture concentration and follows an Arrhenius type relationship. The moisture profiles in the meat emulsion during processing were very steep at the product surface. PMID- 22055708 TI - Electrical stimulation of rats: A model for evaluating low voltage stimulation parameters. AB - Anaesthetised rats, used either before or after exsanguination, provided a useful preparation with which to measure muscle tension from the M. triceps surae and follow pH changes from the M. longissimus dorsi due to stimulation. With square wave pulses (5 ms duration) the minimum voltage required to elicit a tension response from the M. triceps surae was 0.1 V when applied via the tibial branch of the sciatic nerve and nearly 3 V when applied directly across the muscles. Maximum responses were achieved by 2 V applied to the nerve or 5-8 V across the muscle. The fusion frequency was higher than the ox, occurring at about 30 pulses per second. There was no response (with voltages less than 8 V) from the same preparation when the rats were curarised. Tension responses of curarised rats, approaching those of normal direct stimulation, were achieved around 20-40 V. Stimulation of the whole rat carcass at 20 V resulted in a pH fall in the M. longissimus dorsi and M. triceps surae. most of which occurred in the first 30 s. The rate of fall of pH following stimulation of M. longissimus dorsi was approximately 0.6 pH units per hour, being considerably greater than the 0.4 pH units per hour for unstimulated rats. As the ultimate pH of rats was high (pH 6.1 6.3), short stimulation times had to be used to avoid asymptotic portions of the curve. Although responses of rat muscles are different from those of bovine or ovine muscles, they show many of the principles which can be used to evaluate stimulation characteristics. PMID- 22055709 TI - The tensile properties of frozen and thawed lean beef. AB - The tensile properties of frozen beef are relevant to many size reduction operations in frozen meat processing. The tensile properties of lean beef aligned both along, and perpendicular to, the fibre direction have been studied over the temperature range +10 degrees C to -30 degrees C and over a range of strain rates. Strain rate had an effect on tensile strength and other tensile parameters for frozen beef with either fibre orientation. Two distinct types of behaviour were observed. At the higher temperatures (e.g. -5 degrees C and -10 degrees C for beef oriented perpendicular to the fibre direction) there was a rise in tensile strength with increase in strain rate. This viscoelastic fracture behaviour can be attributed to the viscoelastic character of meat proteins and also to the plasticity of ice. At the lower temperatures (e.g. -15 degrees C to 30 degrees C for beef oriented perpendicular to the fibre direction) there was a decrease in tensile strength with increase in strain rate. This fracture behaviour can be attributed to the brittleness of ice. Temperature had a marked effect on all tensile parameters. The maximum tensile strength at most strain rates occurred in the temperature range -10 degrees C to -20 degrees C, and the strength was lower at -30 degrees C than at -20 degrees C. PMID- 22055710 TI - The ultra rapid chilling of pork. AB - Pork carcasses and sides were ultra rapidly chilled in air at -30 degrees C and 1 m/s for 4 h and compared with controls chilled in air at 0 degrees C and 0.5 m/s for 24 h. All the required heat was removed during the 4-h process, there was a 1% saving in evaporative weight loss, the pork could be cut and packed immediately and there were no important differences in appearance and bacteriological quality. The loin from sides, but not carcasses, froze during chilling and showed a fourfold increase in drip loss. Loins from both sides and carcasses were tougher than the controls. PMID- 22055711 TI - Benzophenone-containing fatty acids and their related photosensitive fluorescent new probes: design, physico-chemical properties and preliminary functional investigations. AB - Hydrophobic photoaffinity labeling is a powerful strategy to identify hydrophobic segments within molecules, in particular membrane proteins. Here we report the design and synthesis of a novel family of fluorescent and photosensitive lipid tools, which have a common amino acid scaffold functionalized by three groups: (i) a first fatty acid chain grafted with a photoactivatable benzophenone moiety (Fatty Acid BenzoPhenone, FABP), (ii) a second fatty acid chain to ensure anchoring into a half-bilayer or hydrophobic environment, and (iii) a fluorescent carboxytetramethylrhodamine headgroup (CTMR) to detect the photolabeled compound. We present data of the synthesis and characterization of three lipid tools whose benzophenone ring is situated at various distances from the central scaffold. We could therefore establish structure/properties relationships dependent upon the depth of insertion of benzophenone into the membrane. Our lipid tools were extensively characterized both physico- and bio-chemically, and we assessed their functionality in vitro using bacterioRhodopsin (bR). We thus provide the scientific community with novel and reliable tools for the identification and study of hydrophobic regions in proteins. PMID- 22055712 TI - Thio- and aminocaffeine analogues as inhibitors of human monoamine oxidase. AB - In a recent study it was shown that 8-benzyloxycaffeine analogues act as potent reversible inhibitors of human monoamine oxidase (MAO) A and B. Although the benzyloxy side chain appears to be particularly favorable for enhancing the MAO inhibition potency of caffeine, a variety of other C8 oxy substituents of caffeine also lead to potent MAO inhibition. In an attempt to discover additional C8 substituents of caffeine that lead to potent MAO inhibition and to explore the importance of the ether oxygen for the MAO inhibition properties of C8 oxy substituted caffeines, a series of 8-sulfanyl- and 8-aminocaffeine analogues were synthesized and their human MAO-A and -B inhibition potencies were compared to those of the 8-oxycaffeines. The results document that the sulfanylcaffeine analogues are reversible competitive MAO-B inhibitors with potencies comparable to those of the oxycaffeines. The most potent inhibitor, 8-{[(4 bromophenyl)methyl]sulfanyl}caffeine, exhibited an IC(50) value of 0.167 MUM towards MAO-B. While the sulfanylcaffeine analogues also exhibit affinities for MAO-A, they display in general a high degree of MAO-B selectivity. The aminocaffeine analogues, in contrast, proved to be weak MAO inhibitors with a number of analogues exhibiting no binding to the MAO-A and -B isozymes. The results of this study are discussed with reference to possible binding orientations of selected caffeine analogues within the active site cavities of MAO-A and -B. MAO-B selective sulfanylcaffeine derived inhibitors may act as lead compounds for the design of antiparkinsonian therapies. PMID- 22055713 TI - Synthesis and antimalarial evaluation of novel isocryptolepine derivatives. AB - A series of mono- and di-substituted analogues of isocryptolepine have been synthesized and evaluated for in vitro antimalarial activity against chloroquine sensitive (3D7) and resistant (W2mef) Plasmodium falciparum and for cytotoxicity (3T3 cells). Di-halogenated compounds were the most potent derivatives and 8 bromo-2-chloroisocryptolepine displayed the highest selectivity index (106; the ratio of cytotoxicity (IC(50)=9005 nM) to antimalarial activity (IC(50)=85 nM)). Our evaluation of novel isocryptolepine compounds has demonstrated that di halogenated derivatives are promising antimalarial lead compounds. PMID- 22055714 TI - Electron-donating para-methoxy converts a benzamide-isoquinoline derivative into a highly Sigma-2 receptor selective ligand. AB - The sigma-2 (sigma2) receptor has been suggested to be a promising target for pharmacological interventions to curb tumor progression. Development of sigma2 specific ligands, however, has been hindered by lack of understanding of molecular determinants that underlie selective ligand-sigma2 interactions. Here we have explored effects of electron donating and withdrawing groups on ligand selectivity for the sigma2 versus sigma1 receptor using new benzamide isoquinoline derivatives. The electron-donating methoxy group increased but the electron-withdrawing nitro group decreased sigma2 affinity. In particular, an extra methoxy added to the para-position (5e) of the benzamide phenyl ring of 5f dramatically improved (631 fold) the sigma2 selectivity relative to the sigma1 receptor. This para-position provided a sensitive site for effective manipulation of the sigma receptor subtype selectivity using either the methoxy or nitro substituent. Our study provides a useful guide for further improving the sigma2 over-sigma1 selectivity of new ligands. PMID- 22055715 TI - Relevance of the C-5 position to schweinfurthin induced cytotoxicity. AB - The schweinfurthins are an intriguing group of anti-proliferative agents that display low nanomolar activities against several cell types, including the human derived glioblastoma cell line SF-295, but have little impact on other cell lines even at micromolar concentrations. This activity has inspired the synthesis of seven of the natural schweinfurthins, all with the correct absolute stereochemistry, and a variety of analogues designed to probe different facets of the pharmacophore. Reported herein is the synthesis of several new schweinfurthin analogues varied at the C-5 position along with data on their biological activity in the NCI 60 cell-line assay. PMID- 22055716 TI - Further structure-activity relationship studies on 8-substituted-3-[2 (diarylmethoxyethylidenyl)]-8-azabicyclo[3.2.1]octane derivatives at monoamine transporters. AB - The synthesis and structure-activity relationships of 8-substituted-3-[2 (diarylmethoxyethylidenyl)]-8-azabicyclo[3.2.1]octane derivatives were investigated at the dopamine transporter (DAT), the serotonin transporter (SERT) and norepinephrine transporter (NET). The rigid ethylidenyl-8 azabicyclic[3.2.1]octane skeleton imparted modestly stereoselective binding and uptake inhibition at the DAT. Additional structure-activity studies provided a transporter affinity profile that was reminiscent of the structure-activity of GBR 12909. From these studies, the 8-cyclopropylmethyl group has been identified as a unique moiety that imparts high SERT/DAT selectivity. In this study the 8 cyclopropylmethyl derivative 22e (DAT K(i) of 4.0 nM) was among the most potent compounds of the series at the DAT and was the most DAT selective ligand of the series (SERT/DAT: 1060). Similarly, the 8-chlorobenzyl derivative 22g (DAT K(i) of 3.9 nM) was found to be highly selective for the DAT over the NET (NET/DAT: 1358). PMID- 22055717 TI - Synthesis and evaluation of inhibitors of bacterial drug efflux pumps of the major facilitator superfamily. AB - Inhibitors of drug efflux pumps have great potential as pharmacological agents that restore the drug susceptibility of multidrug resistant bacterial pathogens. Most attention has been focused on the discovery of small molecules that inhibit the resistance nodulation division (RND) family drug efflux pumps in Gram negative bacteria. The prototypical inhibitor of RND-family efflux pumps in Gram negative bacteria is MC-207,110 (Phe-Arg-beta-naphthylamide), a C-capped dipeptide. Here, we report that C-capped dipeptides inhibit two chloramphenicol specific efflux pumps in Streptomyces coelicolor, a Gram-positive bacterium that is a relative of the human pathogen Mycobacterium tuberculosis. Diversity oriented synthesis of a library of structurally related C-capped dipeptides via an Ugi four component reaction and screening of the resulting compounds resulted in the discovery of a compound that is threefold more potent as a suppressor of chloramphenicol resistance in S. coelicolor than MC-207,110. Since chloramphenicol resistance in S. coelicolor is mediated by major facilitator superfamily drug efflux pumps, our findings provide the first evidence that C capped dipeptides can inhibit drug efflux pumps outside of the RND superfamily. PMID- 22055718 TI - Structure-activity relationships of chalcone analogs as potential inhibitors of ADP- and collagen-induced platelet aggregation. AB - In an effort to develop potent antiplatelet agents, 12 O-prenylated (2-13) and 10 O-allylated (14-23) chalcones were synthesized and screened for in vitro inhibitory effects on aggregation of washed rabbit platelets induced by ADP (20 MUM) and collagen (10 MUg/mL). In addition, the platelet aggregation activity of previously synthesized Mannich bases of heterocyclic chalcones (MBHC) (24-62) was evaluated. The preliminary structure-activity relationships suggested that the antiplatelet activity was governed to a great extent by the presence of a pyridyl ring-B and a hydroxy group at position C-3' in ring-A of the MBHC templates. PMID- 22055719 TI - FUS mutations in sporadic amyotrophic lateral sclerosis: clinical and genetic analysis. AB - Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited form of amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmic accumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we have performed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patients carrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic position have been observed in 2 patients: R521G and R521C respectively; P525L mutation has been found in 2 additional cases. Most of the patients with FUS mutations showed early symptom onset and had short disease survival. We also detected 4 different polymorphic variants (3' untranslated region [UTR] variant, c.*41G>A; c.523+3ins[GAGGTG]; c.335 15del[TTTT]; and rs13331793) in 9 patients from within our cohort. This study underlines the importance of population-based mutation screening of newly identified genes. PMID- 22055720 TI - Letter regarding Flecher et al. "Cancer on a pacemaker lead" - is it MICE (Mesothelial Incidental Cardiac Excrescence)? PMID- 22055722 TI - Effect of frozen storage and protective packaging on lipid oxidation in pork backfat with slightly increased levels of polyenoic fatty acids. AB - Backfats with slightly increased levels of polyenoic fatty acids (up to about 15.0%) were obtained by fattening pigs with diets containing increasing amounts of corn cob mix (an ensiled corn and cob mixture). The diet with the highest CCM content was also supplemented with 100ppm dl-alpha-tocopheryl acetate. Cuts of backfat were stored up to 9 months at -20 degrees C in the dark, packed under vacuum (Suprovac bags) and in polyethylene pouches. During and after storage no evidence of rancidity was observed for any of the samples. With regard to lipid oxidation, no significant advantage of sealing under vacuum, compared with packaging in polyethylene pouches, was observed. Lipids in the backfats produced on the diet supplemented with dl-alpha-tocopheryl acetate appeared slightly more stable towards oxidation than the fats obtained with the regular diet. However, as a shelf life of over 9 months at -20 degrees C for packaged backfat is considered quite acceptable, supplementation of the rations with dl-alpha tocopheryl acetate for this commodity does not appear recommendable. PMID- 22055723 TI - Controlling growth of Streptococcus faecium in a ham model with heat and ethylenediamine tetraacetic acid, tertiary butylhydroquinone or nisin. AB - The study described in this paper was designed to test the effect of heat and EDTA, TBHQ or nisin on the stability of a ham model with regard to Streptococcus faecium. Comminuted ham tissue containing brine and test ingredients was inoculated with two strains of Str. faecium and heated for 0, 30, 60, 90 and 120 min at 68.9 degrees C. Growth was followed during incubation at 7 degrees C and 37 degrees C. In combination with heating at 68.9 degrees C for 30 min, a stable (180 days 7 degrees C) model was obtained by adding (ppm): 400, EDTA; 1000, TBHQ or 20, nisin. EDTA and nisin seem promising compounds for enhancing the stability of pasteurized ham with regard to Str. faecium. PMID- 22055724 TI - Meat from Sudan desert sheep and goats: Part 1-Carcass yield, offals and distribution of carcass tissues. AB - Twenty yearling, male Sudan desert sheep and a similar number of desert goats were used in the study. Within each species the animals were equally divided into two groups. Each group was randomly assigned to control or fattened treatment. The control group was slaughtered at the beginning of the experiment and the fattened group slaughtered after 60 days in feedlot. Feedlot performance, slaughter and carcass data were collected. Sheep made faster gains and utilized food more efficiently than goats. The difference between sheep and goats (d) in overall body gain per head was 4.9 +/- 0.67 kg. Sheep had heavier carcasses (d = 0.70 +/- 0.19 kg) and side fat (d = 0.19 +/- 0.06 kg) than goats at an equally adjusted empty body or side weight, respectively. Goats tended to have 0.02 +/- 0.04 kg more muscle and 0.06 +/- 0.05 kg more bone than sheep in carcass side. The subcutaneous fat was poorly developed in both species. The intermuscular fat was more developed, and cavity fat (kidney + thoracic and pelvic cavity fat) less developed, in sheep than in goats. It is possible that the unfavourable fat distribution in goats may affect cookability and eating quality of their meat. PMID- 22055725 TI - Meat from Sudan desert sheep and goats: Part 2-Composition of the muscular and fatty tissues. AB - Muscle fibre diameter and proximate chemical compositions were investigated in forty Sudan desert sheep and goats on two treatments-control and fattened. The fatty acid composition of fat depots from the fattened animals was also determined. Sheep had thinner fibres, more intramuscular fat and less muscle protein than goats. Sheep responded to the nutritional treatment by depositing more fat and goats responded by laying down more muscle protein. The fatty acids composition of subcutaneous, kidney and intermuscular fat depots was reasonably similar in both species but goats tended to have more oleic acid in their fat depots than sheep. The results suggest that goat meat is not inferior to mutton from a nutritional viewpoint. Consumption of goat meat should be encouraged in the Sudan, especially within the low-income groups, to meet their needs for protein. PMID- 22055726 TI - Testosterone and the incidence of boar taint: Effects of testosterone or testosterone propionate on the incidence of boar taint in implanted barrows. AB - Boars, barrows and barrows implanted with testosterone or testosterone propionate via polydimethylsiloxane (Silastic) capsules were placed on test in individual pens at 10 weeks of age. Each animal was slaughtered at 110 kg and evaluated for growth rate, efficiency of feed utilization, carcass merit and the incidence of objectionable odors (boar taint). Five capsules of testosterone or testosterone propionate were used in barrows since they substantially elevated concentrations of serum testosterone, decreased serum LH and stimulated weights of the accessory sex glands. Large variations within and between litters of pigs were found for performance and carcass traits; thus, the influences of castration and testosterone replacement therapy on these traits were inconclusive. In contrast, the effects of castration and hormone treatment on the incidence of boar taint were more definitive. The incidence of boar taint was relatively high in boars, according to a consumer taste panel. This characteristic odor was appreciably lower in barrows and was not reinstated with either testosterone or testosterone propionate implants. These results suggest that testosterone is not itself responsible for boar taint and that 5alpha-androstenone, the pheromone most closely associated with boar taint, is not produced by peripheral metabolism of testosterone. Additional studies are warranted to provide insight into the regulation of testicular steroid secretion in the boar and the contribution of these steroids to boar taint and protein anabolism. PMID- 22055727 TI - Profile of fiber types in muscles from wild pigs native to the United States. AB - Histochemical and histological parameters of the longissimus (LD) and semitendinosus (dark and light portions) muscles from wild pigs native to Florida, USA, were investigated. All three fiber types were present in both muscles at varying proportions with typical (red fibers grouped in clumps and surrounded by white fibers) fiber arrangements for domestic porcine muscles (Cassens, 1971), contrary to the findings by Rahelic & Puac (1981), who examined the LD muscle of wild pigs native to Yugoslavia. These authors foud only betaR fibers present in the LD muscle. In five of the six pigs in the present study, extremely and abnormally large fibers (giant fibers), possessing betaR fiber characteristics, were observed. These giant fibers were found in both the LD and the semitendinosus (dark and light portions) and were not restricted to the periphery of the fasiculi. The presence of these giant fibers suggests some type of muscle myopathy syndrome in these pigs. PMID- 22055728 TI - The role of IL-15 in challenging Acquired Immunodeficiency Syndrome. AB - OBJECTIVE: To determine the functions of in vitro primed Natural Killer (NK) cells in Human Immunodeficiency Virus (HIV-1) infection and the role of IL-2, IL 12 and IL-15 in enhancing the NK survival and activity in terms of viral suppression and of purging of HIV provirus. METHODS: Peripheral Blood Mononuclear Cells (PBMCs) and CD4+ T lymphocytes cells obtained from eight healthy donors were infected in vitro with HIV-1 and p24 was measured with and without IL-2, IL 12 and IL-15. We studied the effect of NK pulsed in vitro with IL-2, IL-12 and IL 15 on HIV replication by measurement of p-24 and DNA-provirus load when added into the culture of PBMCs and CD4+ T lymphocytes cells infected in vitro. We evaluated the effect of NK cells pulsed with IL-2, IL-12 and IL-15 on HIV replication and DNA-load into the culture of CD4+ T lymphocytes cells and PBMCs by trans-well chamber. RESULTS: We found high levels of p24 in the supernatants of PBMCs and CD4+ T lymphocytes cells cultured with IL-2, IL-12, and IL-15. We observed a significant reduction of p24 in the culture both of infected PBMCs and CD4+ T lymphocytes cells in which was added NK pulsed with IL-15. We did not obtain the some results with NK pulsed with IL-2 and IL-12. We observed a power effect of NK pulsed with IL-15 on HIV-DNA. The trans-well chamber experiments showed that the effect of NK is both direct and both mediated by realizing of soluble factors. CONCLUSIONS: This study highlights some important effects of IL 15 on NK in HIV patients anyway our results are preliminary and descriptive and others studies will be needed to provide rationale for immune therapies. PMID- 22055729 TI - Predictors of successful salpingo-oophorectomy at the time of vaginal hysterectomy. AB - STUDY OBJECTIVE: To determine prognostic factors related to successful salpingo oophorectomy in menopausal women at the time of vaginal hysterectomy. DESIGN: Retrospective cohort study (Canadian Task Force Classification II-2). SETTING: Tertiary care center. PATIENTS: A total of 309 postmenopausal >=60 years old with pelvic floor disorders. INTERVENTIONS: Vaginal hysterectomy with attempted prophylactic salpingo-oophorectomy. MEASUREMENTS: Factors associated with ability to achieve vaginal salpingo-oophorectomy. MAIN RESULTS: 203 (65.7%) achieved successful removal of 1 or both ovaries, and 106 (34.3%) were not amenable to removal. Younger age and shorter cervical length were predictors of salpingo oophorectomy. Cervical elongation of >=7 cm, exteriorized cervical/uterine prolapse, and anterior vaginal wall prolapse beyond the hymen were associated with lower likelihood of achieving salpingo-oophorectomy. CONCLUSIONS: Patient age and cervical length are independent factors that influence the success of accomplishing salpingo-oophorectomy at the time of vaginal hysterectomy. PMID- 22055730 TI - Microbiological and sensory characteristics of beef loin steaks: Role of subcutaneous fat. AB - Beef loin steaks with the subcutaneous fat attached, without subcutaneous fat and the subcutaneous fat that was removed from steaks were packaged and stored at 4 degrees C +/- 1 degrees C in polyvinyl chloride (PVC) film for 0-6 days and in high-oxygen barrier (HOB) film for 0-28 days. Aerobic plate counts (APCs) of subcutaneous fat of intact steaks and of subcutaneous fat that was packaged and stored separately in PVC and HOB films were greater (P < 0.05) than those of comparable lean samples. The APCs of lean of steaks without subcutaneous fat that were packaged and stored in HOB film were lower (P < 0.05) than those of the lean of intact steaks. APCs of the lean of these two types of steaks packaged and stored in PVC film did not differ (P > 0.05). Mean surface discoloration and mean overall appearance scores of intact steaks packaged and stored in HOB film were greater than those of steaks packaged and stored without subcutaneous fat; differences were significant (P < 0.05) after 21 and 14 days, respectively. This difference in surface discoloration was attributed to metmyoglobin formation due to possibly higher levels of oxygen remaining in the packages of steaks without subcutaneous fat than in packages containing steaks with the fat attached. PMID- 22055731 TI - Development of backfat and individual fat layers in the pig and its relationship with carcass lean. AB - The development of backfat (total and individual layers) was monitored in 140 Yorkshire pigs (71 castrates and 69 gilts) during a growing period extending from 14.5 kg to 137.0 kg live weight using a serial slaughter procedure. The allometric coefficient (b) for fat thickness was calculated at several locations extending from the shoulder to the M. gluteus medius at the mid-line and lateral to the mid-line. The relationships between backfat (total and individual layers) and the yield of trimmed boneless meat were also obtained from 80 carcasses. Total backfat was the thickest at the shoulder, decreased gradually to the last rib, increased at the maximum loin, decreased to the middle of the M. gluteus medius and then increased posterior to the M. gluteus medius. The development of total backfat relative to weight at slaughter was generally slowest at the shoulder (b = 0.555-0.767), most rapid in the region extending from the 5/6 last rib to the last rib b = 0.729-0.810) and intermediate at the loin and in the region of the M. gluteus medius (b = 0.609-0.834). The development of the middle fat layer (b = 0.609-1.107) was more rapid than that of the outer layer (b = 0.500-0.817), the inner layer being intermediate (b = 0.515-0.966). Consistent with the rate of development observed for the individual fat layers, at light weights, the outer layer was usually more predominant, particularly at positions above the M. longissimus, whereas, at heavier weights, the middle layer became predominant. It was observed that backfat (total or individual layers) measurements, which were the most precise predictors of yield of trimmed boneless meat, that is, measurements from the 5/6 last rib to the last rib (RSE = 4.6 3.1), also had the most rapid rate of development. Furthermore, the middle layer of backfat which exhibited the fastest rate of development of all three individual layers (b = 0.609-1.107), also contributed the most to the observed precision (RSE = 4.6-3.1). PMID- 22055732 TI - Effects of electrical stimulation, followed by moderate cooling, on meat quality characteristics of veal Longissimus dorsi. AB - Three groups of male Friesian veal calves (in total, 92) were slaughtered in separate series. Within each group, a subgroup (selected on the basis of blood characteristics determined 1 week ante mortem) was electrically stimulated immediately after bleeding (64 s-Mitab(r) Low voltage unit). Carcasses were transferred ca. 25 min post mortem (pm) to a cooler at 6 degrees C and ca 2 h pm to a cooler at 3 degrees C. Electrical stimulation (ES) increased brightness and, to a lesser extent, yellowness, of the freshly cut surface (6th rib Longissimus dorsi, 24 h pm) but resulted also in a diminished water-holding capacity (WHC) of the veal meat. The effect of ES on tenderness (Warner-Bratzler shear force, 48 h pm) is positive for two of the three groups but negative for the third. This indicates that ES probably results in two opposite effects on tenderness 'toughening', as a result of the sarcomere shortening which occurred in all three groups, and 'tenderizing', as a result of microscopical fibre disruption. Our data indicate that disadvantages of ES may outweigh advantages when followed by moderate cooling. PMID- 22055733 TI - Effects of low-voltage electrical stimulation during exsanguination on meat quality and display colour stability. AB - Five steers from each of four slaughter groups were randomly assigned to a low voltage electrical stimulation (LVES) treatment during exsanguination (within 5 min after stunning) and five served as controls (C). LVES consisted of 50V of 60 Hz alternating current (1 s on and 1 s off for 2 min). At 28 h, LVES longissimus (LM) was lighter in colour, softer, coarser in texture and tended to have lower marbling estimates than C. LVES LM steaks were lighter red at 0 and 1 days, but more discoloured at 5 days, of display than C steaks. Both the deep (DSM) and superficial (SSM) portions of LVES semimembranosus (SM) steaks were lighter red at 0 and 1 days of display than C steaks. Water-holding capacity for LVES LM and DSM steaks was lower than for C steaks. A trained sensory panel found LVES LM steaks to be less juicy and less tender than C steaks. Also, LVES LM steaks had greater cooking losses than C steaks in two of the four slaughter groups. We conclude that LVES during exsanguination, coupled with relatively slow initial chilling, may be detrimental to muscle quality. PMID- 22055734 TI - Effects of electrical stimulation and ageing of beef on the gelation properties and protein extractability of isolated myofibrils. AB - The gelation properties of bovine myofibrils, as evaluated by dynamic rheological measurements, were shown to be very sensitive to the variables investigated: stimulation and/or ageing of the meat used, presence of 5 mM pyrophosphate and 5 mM MgCl(2) (PP) and concentration of NaCl (0.3 or 0.M). Statistical evaluation of final gel storage moduli (determined at 70 degrees C) revealed ageing to have a consistent detrimental effect. Fresh, stimulated processing of meat), gave gels of about 40% lower elasticity (storage modulus) than did non-stimulated myofibrils; when PP was included in the gel-forming mixture no effect from electrical stimulation was seen. In spite of the negative effects observed for gel elasticity, the myofibrils in question displayed enhanced protein extractability prior to heating. Electrophoretic results suggest myosin degradation to be partly responsible. PMID- 22055735 TI - A comparison of methods to estimate water-holding capacity in post-rigor porcine muscle. AB - Water-holding capacity (WHC) of muscle is important because it affects both qualitative and quantitative aspects of meat and meat products. For assessment of WHC under field and laboratory conditions, there are several methods available, but they have not been compared in a single experiment to determine accuracy and repeatibility. The Longissimus dorsi from each of 28 porcine loins representing three distinct levels of WHC (DFD, PSE, normal) was separated into eighteen parts that were randomly assigned to individual methods. The following methods were compared: Grau-Hamm and Braunschweiger-Gerat filter paper press techniques using five approaches of evaluation for each method; transmission per cent; swelling due to added water; centrifugation; 48-h fresh and cooked shrink: imbibition of surface fluids, kapillar volumeter, permittivity; and score or weight of surface fluids accumulating on filter paper. Results indicated that most methods separated the three muscle types. However, the cooking loss tests failed to differentiate between PSE and normal samples, and the transmission, imbibition and pressed fluid methods did not always distinguish between DFD and normal. The tests that appeared to be most reliable included drip loss originating from size standardized samples, swelling of homogenized samples by added water and absorption of surface fluids on filter paper. PMID- 22055736 TI - Letter to the editor. PMID- 22055737 TI - Making connections between the brain and behavior. Invited commentary on "Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders" by R.K. Kana, L.E. Libero, and M.S. Moore. PMID- 22055738 TI - Is the medium the message? Comment on "Emotional voices in context: a neurobiological model of multimodal affective information processing" by Bruck et al. PMID- 22055739 TI - Oxytocin modulates the link between adult attachment and cooperation through reduced betrayal aversion. AB - An experiment examined whether and how the relationship between individual differences in social attachment and cooperation is modulated by brain oxytocin, a neuropeptide implicated both in parent-child bonding, and in social approach. Healthy males completed a validated attachment style measure, received intranasal oxytocin or placebo, and privately chose between cooperation and non-cooperation in an incentivized social dilemma with an anonymous stranger. Attachment anxiety- the tendency to fear rejection by others--had few effects and was not modulated by oxytocin. However, oxytocin interacted with attachment avoidance--the tendency to fear dependency and closeness in interpersonal relations. Especially among participants high rather than low in attachment avoidance, oxytocin reduced betrayal aversion, and increased trust and cooperation compared to placebo. Effects of attachment avoidance and oxytocin on cooperation were mediated by betrayal aversion, and not by affiliation tendencies. PMID- 22055740 TI - Techniques for measuring water-binding capacity in muscle foods-A review of methodology. AB - Many methods are available for measuring the WHC (water-holding capacity) of muscle and muscle products. However, not all WHC methods are suitable for a given application and use of an inappropriate method may lead to erroneous conclusions. This paper will first briefly describe the mechanism which immobilizes water in muscle foods, then review the methods currently used for measuring WHC of muscle foods and indicate suitable applications for each method. PMID- 22055741 TI - Characterization of green hams from Iberian pigs by fast analysis of subcutaneous fat. AB - Melting point, slip point, iodine value (fast analyses) and percentage contents of fatty acids were determined in subcutaneous fat of hams from Iberian pigs in order to study the possibilities of characterizing the type of pig feeding and the relationships between the results of fast analysis and fatty acid contents. Both types of analyses showed important differences between samples from pigs fed on acorn and samples from pigs fed on mixed feeds. When a combination of feeding materials (acorn and mixed feeds) was used, the analyses gave intermediate results, closer to those obtained with mixed feeds only. On the other hand, generally high simple and multiple correlation coefficients (greater than 0.85) were obtained between fast analyses and fatty acid contents, which allows accurate predictions using regression and canonical correlation analyses. PMID- 22055742 TI - Butterfat in rations for pigs fed skimmed whey: Growth rate, feed conversion, economics, carcass evaluation and fat quality. AB - An experiment was carried out, using 81 castrated male pigs, to estimate the effect of adding butterfat (70% fat, 30% buttermilk), as an energy supplement, to the rations of pigs fed skimmed whey ad libitum. The rations were fed daily in a restricted amount and butterfat added to rations at two levels: T-2 and T-3, 140 and 280 g/day/animal, respectively. In treatment T-1, no butterfat was added. The pigs were weighed every 21 days until they reached average liveweights of 100 (group 1) or 120 kg (group 2), when they were killed for carcass studies. There were significant differences in liveweight gains and feed conversion for the pigs supplemented with butterfat. A negative result, from an economical point of view, was obtained due to the relatively high price of the butterfat. A higher yield of carcass weight on field liveweight was obtained in treatments T-2 and T-3, reflecting the higher degree of fatness. The relative carcass length, muscle depth and percentage of defatted ham were higher in T-1. Conversely, the relative depth of fat was more marked in the groups and treatments that consumed butterfat with their rations. Both groups of T-1 yielded the highest percentage of muscle and the lowest of fat in their carcasses, the differences from T-2 and T-3 being significant. T-2 and T-3 did not differ significantly from one another. There were significant differences in the fatty acid composition due to sampling location. The differences due to treatment were statistically significant in respect of the concentrations of 14:0, 16:1, 17:0, 17:1, 18:0 and 18:1 fatty acids. The unusually low concentration of 18:2 in the dissected fat tissues produces high quality porcine fats, for use in manifactured and prepared foods. PMID- 22055743 TI - Microbial profiles of minced meat. AB - Minced meat was examined for microbiological quality and for shelf-life at higher temperatures. Total plate counts, coliforms, Staphylococcus aureus, Enterococci and psychrotrophs were estimated. Types of bacteria associated with meat spoilage were isolated and identified. It was observed that minced meat obtained from local retail shops showed significantly higher microbial counts and shorter shelf life than that processed under hygienic conditions. The predominant bacteria associated with fresh meat were S. aureus, Micrococcus and Escherichia. The results revealed that microbial spoilage of meat at higher temperatures was mainly due to the growth of mesophilic microorganisms such as Escherichia and S. aureus. PMID- 22055744 TI - Fatty acid profiles and lipid oxidation in beef steer muscles from different anatomical locations. AB - Beef muscles at four different anatomical locations (longissimus dorsi, LD; psoas major, PM; semimembranosus, SM; semitendinosus, ST) were excised 24 h post-mortem from each of 12 steer carcasses and analyzed for total lipids, fatty acid proofiles and lipid oxidation catalysts. Also, the accumulation of thiobarbituric acid (TBA)-reactive substances in ground muscles stored at 4 degrees C was determined. Total lipids and fatty acid composition of total lipid extracts were similar among the muscles from different locations. The microsomal enzymic lipid peroxidation activity was higher for the ST than for other muscles whereas total heme pigment was lower for the ST than for others. The nonheme iron was higher for the PM and SM than for the LD and ST. The accumulation of TBA-reactive substances in stored, raw ground muscle was highest for the PM and lowest for the LD. TBA values of ground muscle samples were positively correlated with heme pigment content and microsomal enzymic lipid peroxidation activity while not correlated with nonheme iron content. It also was positively correlated with the percentage of polyunsaturated fatty acids. PMID- 22055745 TI - Composition of muscle fibre types and connective tissue in bovine M. semitendinosus and its relation to tenderness. AB - The distribution of muscle fibre types and connective tissue in bovine M. semitendinosus is described. A parallel increase in the volume fraction of type I muscle fibres (from 10% to 30%) and a decrease in the IIB volume fraction (from 58% to 34%) was recorded from superficial to deep layers. A positive correlation was observed between the frequency and the cross-sectional area of both type I and IIB fibres. The elastic fibres formed irregularly shaped bundles that made up about 50% of the volume of the perimysium. Thin elastic fibres extended into the endomysium. The relative proportion of elastic fibres in the perimysial connective tissue increased towards the deeper layers of the muscle. A taste panel evaluation of the sensory properties was performed and the data were correlated to the histological observations. A gradual decrease in scores of four tenderness-related traits was recorded from the superficial to the deep layer of the muscle. The superficial layer was rated as most tender, whereas the consecutive layers were rated less tender. The possible relationship between the composition of muscle and the meat quality is discussed. PMID- 22055746 TI - A volume microstrip RF coil for MRI microscopy. AB - Quantitative magnetic resonance imaging (MRI) studies of small samples such as a single cell or cell clusters require application of radiofrequency (RF) coils that provide homogenous B(1) field distribution and high signal-to-noise ratio (SNR). We present a novel design of an MRI RF volume microcoil based on a microstrip structure. The coil consists of two parallel microstrip elements conducting RF currents in the opposite directions, thus creating homogenous RF field within the space between the microstrips. The construction of the microcoil is simple, efficient and cost-effective. Theoretical calculations and finite element method simulations were used to optimize the coil geometry to achieve optimal B(1) and SNR distributions within the sample and predict parameters of the coil. The theoretical calculations were confirmed with MR images of a 1-mm diameter capillary and a plant obtained with the double microstrip RF microcoil at 11.7 T. The in-plane resolution of MR images was 24 MUm * 24 MUm. PMID- 22055747 TI - Nuclear norm-regularized SENSE reconstruction. AB - SENSitivity Encoding (SENSE) is a mathematically optimal parallel magnetic resonance (MRI) imaging technique when the coil sensitivities are known. In recent times, compressed sensing (CS)-based techniques are incorporated within the SENSE reconstruction framework to recover the underlying MR image. CS-based techniques exploit the fact that the MR images are sparse in a transform domain (e.g., wavelets). Mathematically, this leads to an l(1)-norm-regularized SENSE reconstruction. In this work, we show that instead of reconstructing the image by exploiting its transform domain sparsity, we can exploit its rank deficiency to reconstruct it. This leads to a nuclear norm-regularized SENSE problem. The reconstruction accuracy from our proposed method is the same as the l(1)-norm regularized SENSE, but the advantage of our method is that it is about an order of magnitude faster. PMID- 22055748 TI - Diffusion-weighted imaging in the prostate: an apparent diffusion coefficient comparison of half-Fourier acquisition single-shot turbo spin-echo and echo planar imaging. AB - Prostate cancer detection using diffusion-weighted imaging is highly affected by the accuracy of the apparent diffusion coefficient (ADC) values in an image. Echo planar imaging (EPI) is a fast sequence commonly used for diffusion imaging but has inherent magnetic susceptibility and chemical shift artefacts associated. A diffusion sequence that is less affected by these artefacts is therefore advantageous. The half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence was chosen. The diffusion sequences were compared in image quality, repeatability of the ADC value and the effect on the ADC value with varied b values. Eight volunteers underwent three scans of each sequence, on a 1.5-T Siemens system, using b values of 0, 150, 300, 450, 600, 750, 900 and 1000 s/mm(2). ADC maps were created to address the reproducibility of the ADC value when using two b values compared to eight b values. The ADC value using all b values with the HASTE sequence gave the best performance in all tested categories. Both sequences gave significantly different ADC mean values for two b values compared to when using eight b values (P<.05) suggesting larger error is present when using two b values. HASTE was shown to be an improvement over EPI in terms of repeatability, signal variation within a region of interest and standard deviation over the volunteer set. The improved accuracy of the ADC value in the HASTE sequence makes it potentially a more sensitive tumor detection technique. PMID- 22055749 TI - Gas challenge-blood oxygen level-dependent (GC-BOLD) MRI in the rat Novikoff hepatoma model. AB - PURPOSE: The purpose of the study was to investigate the relationship between gas challenge-blood oxygen level-dependent (GC-BOLD) response angiogenesis and tumor size in rat Novikoff hepatoma model. MATERIALS AND METHODS: Twenty adult male Sprague-Dawley rats (weighting 301-325 g) were used for our Animal Care and Use Committee-approved experiments. N1-S1 Novikoff hepatomas were grown in 14 rats with sizes ranging from 0.42 to 2.81 cm. All experiments were performed at 3.0 T using a custom-built rodent receiver coil. A multiple gradient-echo sequence was used for R2* measurements, first during room air (78% N(2)/20% O(2)) breathing and then after 10 min of carbogen (95% O(2)/5% CO(2)) breathing. After image acquisition, rats were euthanized, and the tumors were harvested for histological evaluation. RESULTS: The R2* change between air and carbogen breathing for small hepatomas was positive; R2* changes changed to negative values for larger hepatomas. We found a significant positive correlation between tumor R2* change and tumor microvessel density (MVD) (r=0.798, P=.001) and a significant inverse correlation between tumor R2* change and tumor size (r=-0.840, P<.0001). CONCLUSIONS: GC-BOLD magnetic resonance imaging measurements are well correlated to MVD levels and tumor size in the N1-S1 Novikoff hepatoma model; GC-BOLD measurements may serve as noninvasive biomarkers for evaluating angiogenesis and disease progression and/or therapy response. PMID- 22055750 TI - Effect of off-frequency sampling in magnetic resonance elastography. AB - In magnetic resonance elastography (MRE), shear waves at a certain frequency are encoded through bipolar gradients that switch polarity at a controlled encoding frequency and are offset in time to capture wave propagation using a controlled sampling frequency. In brain MRE, there is a possibility that the mechanical actuation frequency is different from the vibration frequency, leading to a mismatch with encoding and sampling frequencies. This mismatch can occur in brain MRE from causes both extrinsic and intrinsic to the brain, such as scanner bed vibrations or active damping in the head. The purpose of this work was to investigate how frequency mismatch can affect MRE shear stiffness measurements. Experiments were performed on a dual-medium agarose gel phantom, and the results were compared with numerical simulations to quantify these effects. It is known that off-frequency encoding alone results in a scaling of wave amplitude, and it is shown here that off-frequency sampling can result in two main effects: (1) errors in the overall shear stiffness estimate of the material on the global scale and (2) local variations appearing as stiffer and softer structures in the material. For small differences in frequency, it was found that measured global stiffness of the brain could theoretically vary by up to 12.5% relative to actual stiffness with local variations of up to 3.7% of the mean stiffness. It was demonstrated that performing MRE experiments at a frequency other than that of tissue vibration can lead to artifacts in the MRE stiffness images, and this mismatch could explain some of the large-scale scatter of stiffness data or lack of repeatability reported in the brain MRE literature. PMID- 22055751 TI - An anisotropic images segmentation and bias correction method. AB - Intensity inhomogeneities cause considerable difficulty in the quantitative analysis of magnetic resonance (MR) images. Thus, bias field correction is a necessary step before quantitative analysis of MR data can be undertaken. This paper presents an anisotropic approach to bias correction and segmentation for images with intensity inhomogeneities and noise. Intensity-based methods are usually applied to estimate the bias field; however, most of them only concern the intensity information. When the images have noise or slender topological objects, these methods cannot obtain accurate results or bias fields. We use structure information to construct an anisotropic Gibbs field and combine the anisotropic Gibbs field with the Bayesian framework to segment images while estimating the bias fields. Our method is able to capture bias of quite general profiles. Moreover, it is robust to noise and slender topological objects. The proposed method has been used for images of various modalities with promising results. PMID- 22055752 TI - Zebrafish embryos sequester and retain petrochemical combustion products: developmental and transcriptome consequences. AB - Zebrafish embryos are a model for studying effects of environmental stressors on development. Incomplete combustion of the environmentally relevant volatile petrochemical, 1,3-butadiene (BD) yields butadiene soot (BDS) nanoparticles, to which polynuclear aromatic hydrocarbons (PAHs) are adsorbed. In mammalian cells these PAHs are concentrated in lipid droplets and trigger up-regulation of biotransformation, oxidative stress and inflammatory genes. The present study was designed to determine whether: (a) PAH-rich BDS elicits alterations in zebrafish embryo development; (b) BDS-exposed zebrafish embryos sequester PAHs in select tissues; and (c) developmental abnormalities are correlated with altered gene expression patterns. 1-day old zebrafish embryos were exposed for 48 h to BDS (0, 6, 30 or 60 MUg/ml) sprinkled on the water surface. PAH localization was tracked by fluorescence. Developmental responses (pericardial edema, yolk sac swelling, axial malformations) were monitored by microscopy. Gene expression changes were assessed by gene microarray and qRT-PCR. Our results show that PAHs localized with endogenous lipids in the yolk sac and in hatching gland cells. PAHs were retained at least 8 days after exposures ended. Dose-dependent pericardial and yolk sac edema and axial malformations were prominent and accompanied by up regulation of biotransformation and oxidative stress gene cascades. Thus, zebrafish embryos should be useful for predicting the potential for developmental toxicity following exposure to PAH-rich petrochemical soots, e.g., those arising from attempts at oil spill remediation by combustion. PMID- 22055754 TI - Weight loss in frankfurters during thermal processing. AB - A simplified two-term model was developed to predict the weight loss of frankfurters during thermal processing at various process conditions and with various product compositions. The model was validated with the experimental data. The moisture loss rate was found to be proportional to product temperature and inversely proportional to the fat-protein ratio of the product. PMID- 22055753 TI - Multilocus sequence analysis provides basis for fast and reliable identification of Vibrio harveyi-related species and reveals previous misidentification of important marine pathogens. AB - Vibrio harveyi and related bacteria are important pathogens responsible for severe economic losses in the aquaculture industry worldwide. Phenotypic tests and 16S rRNA gene analysis fail to discriminate species within the V. harveyi group because these are phenotypically and genetically nearly identical. This study used multilocus sequence analysis to identify 36 V. harveyi-like isolates obtained from a wide range of sources in Australia and to re-evaluate the identity of important pathogens. Phylogenies inferred from the 16S rRNA gene and five concatenated protein-coding genes (rpoA-pyrH-topA-ftsZ-mreB) revealed four well-supported clusters identified as V. harveyi, V. campbellii, V. rotiferianus and V. owensii. Results revealed that important V. campbellii and V. owensii prawn pathogens were previously misidentified as V. harveyi and also that the recently described V. communis sp. nov. is likely a junior synonym of V. owensii. Although the MLSA topologies corroborated the 16S rRNA gene phylogeny, the latter was less informative than each of the protein-coding genes taken singularly or the concatenated dataset. A two-locus phylogeny based on topA-mreB concatenated sequences was consistent with the five-locus MLSA phylogeny. Global Bayesian phylogenies inferred from topA-mreB suggested that this gene combination provides a practical yet still accurate approach for routine identification of V. harveyi related species. PMID- 22055755 TI - Effects of body weight, breed and sex on killing-out percentage and non-carcass component weights in lambs. AB - The effects of carcass weight (15, 17, 19 and 21 kg), breed (Clun Forest, Colbred, Suffolk and Hampshire) and sex (castrated male and female) on killing out percentage and non-carcass component weights were investigated in 343 lambs. Apart from omental fat and diaphragm, the contribution of the components to live weight fell as live weight increased (relative growth coefficients on live weight were generally < 1.0) and killing-out percentage increased from 47.5% at 33 kg to 50.8% at 44 kg live weight. In any particular carcass weight group, Cluns, the fattest breed, had the highest killing-out percentage and the lowest offal weights of all the breeds and females, the fatter sex, had slightly lower offal weights than castrated males. In both cases the probable explanation was that the fatter types were more developed and not that there were specific effects on organ or offal weights. Some carcass measurements were related to killing-out percentage and suggested a positive association between conformation and killing out percentage. However, the measurements encompassed fat, as well as muscle and bone, and it was concluded that the primary effect on killing-out percentage was one of fatness rather than conformation. PMID- 22055756 TI - A repeat national survey (ten years on) of muscle pH values in commercial bacon carcasses. AB - Measurements of M. longissimus pH values at 45 min post mortem (pH(1)) were taken in a total of 5383 commercial bacon weight carcasses at fourteen bacon factories and meat plants in 1980/81. Comparable pH(2) values at 24 h post mortem were taken in a further 5150 carcasses. The overall mean pH(1) was 6.38 +/- 0.29 (SD) with 12.8% of values less than 6.0. The overall mean pH(2) was 5.91 +/- 0.18 with 0.6% of values greater than 6.5. Relationships between pH values and carcass weight, fat thickness and length were very low (maximum r = 0.05). Comparison of the results with a similar survey conducted in 1972/73 indicated that the proportion of carcasses with pH(1) values less than 6.0 has doubled (1972/73 result was 5.7%). The proportion of carcasses with high pH(2) values changed little. PMID- 22055757 TI - Thermal tolerance of Lactobacillus viridescens in ham. AB - Lactobacillus viridescens is a ubiquitous organism in meat plants causing a green discoloration of cured meat products, resulting in serious financial losses. Using a method similar to that of Niven et al. (1954) the thermal tolerances of strains isolated from core greening and surface greening were established. It was found that the thermal tolerance of the surface greening strain could be doubled by successive heat shocks. Time-temperature studies of the processing of ham showed that the normal process could not be relied upon to destroy all the organisms present. So, if L. viridescens can adapt itself in industry, as in the laboratory, to be able to withstand the thermal processing, it is possible for the organism to survive heat processing and cause outbreaks of green discolorations in cured meats. Studies showed that the D(65) values for the organism are higher in ham broth and slices than in laboratory media. Thus, ham appears to act as a heat protective agent for L. viridescens. PMID- 22055758 TI - Weight loss from beef sides during storage post mortem and its effects on carcass composition. AB - The effects of storage on carcass weight, carcass composition and the water content of tissues have been investigated. Ten Friesian-cross steer carcasses were used, one side being dissected 1 day after slaughter and the other after storage at + 1 degrees C and 84 % relative humidity for 20 days. The rate of weight loss from the sides (range in hot weight, 103.0 to 201.5 kg) was linear between days 1 and 20, with a mean loss of 4.2 kg (0.17 %/day). During the period of storage, there was a reduction in weight of all tissues except intermuscular fat (IMF) and fatter sides (range 14.72-32.23 % dissectible fat) had a proportionately smaller loss. In percentage composition terms, there was a significant reduction in subcutaneous fat (SCF)of 0.36 percentage units, P < 0.01, and in lean, of 0.59 percentage units, P < 0.05; there was a significant gain in IMF of 0.63 percentage units, P < 0.01, but it was considered that changes were not large enough to seriously affect the interpretations of dissection data in most experiments. During storage, all tissues except IMF lost water, particularly SCF, which lost 28 % of the original amount. In the day 1 sides, 35 % of the total loss from hot weight to recovered tissue weight (after dissection) occurred during jointing and dissection and 65 % during storage. In the day 20 sides, the values were 12 %, and 88 %, respectively. PMID- 22055759 TI - Effect of frozen storage on the structure and enzymatic activities of myofibrillar proteins of rabbit skeletal muscle. AB - The effect of frozen storage on the biochemical properties of myofibrils, and of their major constituents, actin and myosin, was investigated. Extractability of myofibrillar proteins increased slightly for 3 weeks during frozen storage of muscle, decreasing thereafter. The change in myofibrillar ATPase activity during frozen storage was consistent with that of a reconstituted acto-heavy meromyosin (HMM) complex prepared from frozen stored muscle at the same weight ratio of actin to myosin as in situ. However, myosin ATPase activity showed a different pattern of change when compared with myofibrillar ATPase activity. The maximum velocity of acto-HMM ATPase activity and the apparent dissociation constant of the acto-HMM complex decreased for 1 week during frozen storage, increasing thereafter, indicating that the affinity of actin for myosin was greatest in muscle which had been frozen for 1 week. PMID- 22055760 TI - Time of onset of insensibility in four- to six-week-old calves during slaughter. AB - The time of onset of permanent insensibility subsequent to incision of the major blood vessels of the neck was studied in one 31-day-old calf and two 42-day-old calves. Insensibility was determined from the study of electroencephalograms (EEG). Insensibility first occurred at 28, 30 and 168s, respectively. Following respiratory gasps, all three animals subsequently showed resurgences of cerebrocortical activity for periods of between 130 and 187s, and EEGs did not become isoelectric again for 116 to 300s after slaughter. These results are similar to those previously recorded in 1-week-old calves and are in disagreement with the findings of Nangeroni & Kenneth (1963) which indicated that 8-week-old calves became permanently insensible within 6.9s of slaughter. PMID- 22055761 TI - Food proteins Edited by P. F. Fox and J. J. Condon. Applied Science Publishers Ltd, London. 1982. 361 pp. Price: L38.00. PMID- 22055762 TI - Letter to the editor. PMID- 22055763 TI - An economic analysis of dose dense weekly paclitaxel plus carboplatin versus every-3-week paclitaxel plus carboplatin in the treatment of advanced ovarian cancer. AB - OBJECTIVE: Compared with every-3-week paclitaxel (q3T) plus carboplatin, dose dense weekly paclitaxel (ddT) plus carboplatin improved the survival of ovarian cancer patients. We performed a cost analysis comparing these two regimens. METHODS: Using a Markov decision model, an acceptable incremental cost effectiveness ratio (ICER) per progression-free life-year saved (PFLYS) was estimated. Cost of drugs, growth colony-stimulating factors, and transfusions were derived from Medicare reimbursement data. Survival and rates of complications were estimated based on the clinical trial. RESULTS: Using a body weight and surface area of an average woman age 63, the estimated cost per cycle of ddT was $107 vs. $80 for q3T. The costs per cycle of combination chemotherapy including treatment administration were $873 for ddT and $535 for q3T. With a median progression-free survival (PFS) of 28 months with ddT vs. 17.2 months with q3T, the ICER was $5809 per PFLYS for ddT compared with q3T arm. Using a maximum ICER of $100,000 per LYS as cost-effective threshold, the ddT regimen was cost effective. The ICER was most sensitive to the hazard rate for difference in PFS between the two regimens. A 4-month difference in PFS resulted in a $1200 change of ICER per PFLYS. The ICER was also sensitive to overall survival difference, rate of hematological toxicity, and rate of discontinuation. CONCLUSIONS: In this economic model, dose-dense weekly paclitaxel is a cost-effective treatment option for advanced ovarian cancer. PMID- 22055764 TI - Effect of chemotherapy delays and dose reductions on progression free and overall survival in the treatment of epithelial ovarian cancer. AB - INTRODUCTION: Hematologic, gastrointestinal, and neurologic complications are common side effects of the platinum and taxane-based chemotherapy used in the primary treatment of epithelial ovarian cancer (EOC). These side effects and the impact of the resultant chemotherapy dose modification on disease free interval have not been extensively studied. The goal of this study was to determine the effect of chemotherapy delays and dose reductions on progression free survival (PFS) and overall survival (OS). METHODS: A review of patients with primary epithelial ovarian, peritoneal, and fallopian tube carcinoma treated between 1/2000 and 12/2007 was performed. Inclusion criteria were advanced stage disease and first line chemotherapy with a platinum and taxane regimen. Cox proportional hazard models were used to determine the effect of chemotherapy reductions and delays on PFS and OS. RESULTS: One hundred and fifty seven patients met the inclusion criteria. Patients were divided into four groups: no delays or reductions (48%), delay only (27%), reduction only (8%), and both delay and reduction (18%). The mean number of delays/reductions per patient was 1.1 (range=0-5) and therapy was delayed a mean of 8 days. The most common reasons for delays/reductions were neutropenia (n=51), thrombocytopenia (n=45), and neuropathy (n=18). There were no differences detected in PFS or OS between groups. CONCLUSIONS: There were no differences detected in survival between patients who required dose adjustments and treatment delays and those who did not. The lack of association between survival and chemotherapy alterations suggests that in specific circumstances patients with advanced ovarian cancer should have individualized treatment plans. PMID- 22055765 TI - Endobronchial metastases of anal canal carcinoma. AB - Endobronchial metastases (EBM) secondary to extrapulmonary primary tumours are rare. The most common solid malignant tumours associated with EBM are breast, renal and colorectal carcinomas. This case report describes the first documented case of EBM from anal canal carcinoma. This neoplasm constitutes less than 1% of colorectal tumours. The clinical presentation of this entity is variable, being asymptomatic in more than 50% of cases. Generally, EBM are diagnosed in advanced stages and the survival after the diagnosis is poor. It is therefore an exceptional clinical manifestation in which bronchoscopy has an important role in the diagnosis and the treatment. PMID- 22055766 TI - Isokinetic strength and power deficits in the hand following stroke. AB - OBJECTIVE: The purpose of this study was to compare the torque production in the paretic and non-paretic hands during isokinetic tasks following stroke. METHODS: We compared torque and power production at the MCP joint of chronic stroke survivors during isometric and isokinetic tasks. We also recorded surface electromyography (EMG) activity in the forearm muscles. RESULTS: Isokinetic torque production at all velocities was less than that produced during isometric trials. Both torque and power produced by the paretic hand was substantially impaired. Deficits were substantially greater in extension than flexion trials. EMG data suggests that excessive co-contraction of agonist and antagonist muscles does not greatly affect isokinetic torque production at the MCP joint. CONCLUSIONS: The fact that movement velocity produces larger deficits in torque and power production may explain why patients who have limited strength impairments still experience functional deficits. SIGNIFICANCE: This study demonstrates that strength testing of stroke survivors under isometric conditions may underestimate the overall level of impairment. PMID- 22055767 TI - Determination of gamma-gamma' lattice misfit in a single-crystal nickel-based superalloy using convergent beam electron diffraction aided by finite element calculations. AB - In single-crystal nickel-based superalloys, the lattice mismatch associated with interface coherency between gamma matrix and gamma' precipitates has a strong influence on mechanical properties. The unconstrained lattice misfit in a single crystal of the MC2 nickel-based superalloy is determined using convergent beam electron diffraction measurements and finite element calculations. The apparent lattice parameters of both constrained phases are obtained in thin foils, using a new multi-pattern approach, which allows for unambiguous determination of all the lattice parameters considering the real symmetry of the strained crystals. Finite element calculations are used to establish relations between the constrained and unconstrained lattice parameters, with the stress relaxation resulting from the thin foil geometry taken into account. PMID- 22055768 TI - Factors affecting the rate of metmyoglobin accumulation in pre-packaged beef. AB - Factors affecting the rate of discoloration of pre-packaged beef have been compared quantitatively in a number of experimental animals. Inter-muscular variability is the most important single factor and ranges from the stable M. longissimus dorsi to the unstable M. psoas major, the degree of discoloration of the latter muscle being almost eight times greater after 96 h storage at 0 degrees C. Among other intrinsic factors studied, age post mortem has a slight accelerating effect while pH, within the narrow range exhibited by experimental animals, has no effect. Inter-animal variability also has an effect, but only a slight one. Of the extrinsic factors studied, temperature is most important from a practical standpoint, the degree of discoloration after 96 h storage at 10 degrees C ranging from two to five times that at 0 degrees C, depending on the muscle. Light produces only a minor accelerating effect but UV produces serious discoloration in all muscles within hours, even at 0 degrees C. Slight differences exist between packaging films but these are not commercially significant. PMID- 22055769 TI - Relationship between heat transfer parameters and the characteristic damage variables for the freezing of beef. AB - One of the most suitable parameters for relating the freezing rate to the volume of drip produced during the thawing of meat is the characteristic time, defined as the time necessary to reduce the temperature of the sample from -1.1 degrees C (initial freezing point in beef) to -7 degrees C (80% of the water frozen). However, as the freezing of beef in factories takes place with important temperature gradients, distributions of these characteristic times must be expected along the pieces of frozen meat. In order to relate these characteristic time distributions to heat transfer parameters under industrial freezing conditions, a mathematical model which simulates the freezing of beef is developed in this paper. The model establishes the heat transfer equations with simultaneous change of phase, taking into account the dependence of the thermal properties with the ice content and considering the anisotropy of the thermal conductivity according to the direction of the fibres. Boundary conditions include the possibility of thermal resistances in the refrigerated interphase. The model developed was compared with laboratory experiments performed under factory freezing conditions and showed a satisfactory agreement between theory and experiment. PMID- 22055770 TI - An investigation of ultimate pH in the muscles of commercial beef carcasses. AB - Ultimate pH values were recorded in the carcasses of steers and heifers at a beef slaughtering plant over a period of 3 years. The incidence of carcasses with a pH(u) >= 6.0 in the LD-a value usually associated with 'dark-cutting' in beef-was 3.2%. A pronounced seasonal effect was observed with the incidence rising from 1.2% for the period February to August to 5.2% for the period September to January, inclusive. An examination of thirteen muscles showed that increases in pH(u) above normal values occurred most frequently in the LD and four large muscles of the hindquarter and were much less frequently observed in the eight other hind- and forequarter muscles examined. In the carcasses of young bulls, also slaughtered under commercial conditions, high pH(u) values were predominantly associated with the same muscles as in steers and heifers. However, when experimental cattle were given adrenaline to induced high pH(u) values, this treatment resulted in a general increase in pH(u) in all the muscles examined. The different pattern of pH(u) elevation in the adrenaline-treated and commercial carcasses suggests different physiological mechanisms in the two cases. PMID- 22055771 TI - Ultrastructural changes in pre- and post-rigor beef muscle caused by conventional and microwave cookery. AB - Examination of cooked pre-rigor muscle by TEM (transmission electron microscopy) and SEM (scanning electron microscopy) revealed that all cookery methods resulted in the development of supercontraction bands alternating with areas showing tissue fragmentation and tearing. Microwave cookery produced smaller and less dense supercontraction nodes in pre-rigor muscle with less tearing and fragmentation but more fibre separation. Although cold-shortened pre-rigor muscle cooked by all methods also exhibited supercontraction bands with some tearing and fragmentation in adjacent sarcomeres, the samples cooked by microwaves showed a more uniform repeating pattern of small stretched areas alternating with dense contracted areas. Cooking of muscle in full rigor resulted in myofibrillar protein coagulation and shrinkage but supercontraction nodes were absent. Cold shortened bicarbonate treated muscle was relatively intact after cooking, exhibiting fusion of the myofibrils and an absence of intermyofibrillar spaces. Results are discussed in relation to possible effects upon tenderness. PMID- 22055772 TI - The effects of alkaline hydrogen peroxide treatment on the nutritional value of tripe. AB - Samples of tripe obtained after commercial processing with alkaline hydrogen peroxide were compared with raw tripe for nutritional quality. A large number (108) of commercial tripe samples were found to vary markedly in their protein content from 8.4 to 19.3%. The moisture content was negatively correlated with the pH of the tripe samples. However, the amino acid analyses and rat bioassays indicated that the nutritional value of the protein was not significantly decreased by the processing. Oxidation of sulphur amino acids and formation of lysino-alanine were not evident. Thiamine was completely destroyed by the processing. PMID- 22055773 TI - Rapid freezing, frozen storage and the tenderness of lamb. AB - Cold-shortening in pre-rigor lamb can be prevented by freezing carcasses very rapidly in less than four hours. Thaw-shortening can also be prevented by storing the carcasses for a period (> 10 days) in the frozen state (- 12 degrees C). By this simple combination of rapid freezing and frozen storage, the hazard of toughness development from cold- and thaw-shortenings is avoided. PMID- 22055774 TI - Impulse noise exposure in rats causes cognitive deficits and changes in hippocampal neurotransmitter signaling and tau phosphorylation. AB - Noise exposure has been characterized as a stressor, and its non-auditory effects on the central nervous system have been established both epidemiologically and experimentally. Little is known about the impact of impulse noise on the brain, however. In this study, we examined the effects of impulse noise stress on spatial learning and memory and on associated changes in the hippocampus. Rats were exposed to 20 sound impulses with a peak sound pressure of 165 dB and duration of 100 ms. Impulse noise stress led to a temporary decrease in cognitive function as evidenced by poor spatial memory in the Morris water maze (MWM). Effects of noise on the glutamate (Glu)-N-methyl-D-aspartic acid receptor (NMDAR) signaling system and hippocampal tau phosphorylation were investigated by high performance liquid chromatography, Western blotting, and immunohistochemistry. The concentrations of Glu and aspirate (Asp) in the hippocampus were increased at 30 min after exposure and remained elevated for the entire observation period (24 h), while the content of glycine (Gly) was stable for several hours following noise but also increased by 24 h after noise stress. Impulse noise stress also caused a significant increase in NMDAR 2B subunit (NR2B) expression and a two phase increase in tau phosphorylation in hippocampus. Immunohistochemistry confirmed tau hyperphosphorylation in hippocampus that was most prominent in the dentate gyrus (DG) and CA1 region. These findings demonstrate that impulse noise stress impairs early spatial memory, possibly by disrupting Glu-NMDAR signaling and triggering aberrant tau hyperphosphorylation in hippocampus. PMID- 22055775 TI - [Exploration and approach to artificial airway dysphagia]. AB - Airway isolation by endotracheal intubation or tracheostomy impedes or even interrupts speech and swallowing. Pharyngeal and laryngeal impairment frequently occurs after extubation or de-cannulation, common consequences being dysphonia, dysphagia and the aspiration of oral secretions, food, or fluids. Aspiration often leads to pneumonia and eventually death. Although the literature reports a high frequency of dysphagia following intubation and tracheostomy, the data vary considerably, and the true incidence of oropharyngeal dysphagia following artificial airway isolation remains to be established. We conducted a systematic review of the available evidence, in order to assess oropharyngeal dysphagia physiology, diagnosis and treatment. PMID- 22055777 TI - Shortening and tenderness of pre-rigor heated beef: Part 1 - Effect of heating rate on muscles of youthful and mature carcasses. AB - Pre-rigor cooked beef is tender if the cooking produces severe shortening. This study was conducted to compare the effects of different heating rates on shortening and tenderness. Myofibrillar and cooking shortening and related changes were measured with physiograph recordings on pre-rigor M. triceps brachii strips suspended in paraffin oil during heating. Warner-Bratzler shear values were determined on M. triceps brachii samples heated at approximately the same rates at which the muscle strips were heated. Rapid heating (2 degrees C/2min) produced more (p < 0.01) severe myofibrillar shortening that was complete at higher (p < 0.01) muscle temperatures than slow heating (2 degrees C/12 min). Regardless of animal age, rapid heating resulted in a cooked product that was more (p < 0.01) tender than that produced by slow heating in the pre-rigor state and slow heating resulted in a more (p < 0.01) tender product than that achieved by rapid heating in the post-rigor state. Data on muscle shortening and from differential scanning calorimetry suggest that the tenderness produced from pre rigor rapid heating results from a heat-induced active contraction. PMID- 22055776 TI - [Prognostic value of procalcitonin, C-reactive protein and leukocytes in septic shock]. AB - OBJECTIVES: This study evaluates the potential prognostic value of serial measurements of different biomarkers (procalcitonin [PCT], C-reactive protein and leukocytes [CRP]) in septic shock patients. DESIGN: Prospective observational study. SETTING: Intensive care unit of a third-level University Hospital. PATIENTS: The study comprised a total of 88 septic shock patients defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria. The PCT, CRP and leukocytes were recorded on admission to the ICU and again 72 hours after admission. INTERVENTIONS: None. RESULTS: Those patients with increasing procalcitonin levels showed higher hospital mortality than those with a decreasing levels (58.8% vs. 15.4%, P<0.01). No such effect was observed in relation to C-reactive protein or leukocytes. The best area under the curve for prognosis was for procalcitonin clearance (0.79). A procalcitonin clearance of 70% or higher offered a sensitivity and specificity of 94.7% and 53%, respectively. CONCLUSIONS: Serial procalcitonin measurements are more predictive of the prognosis of septic shock patients than single measurements of this parameter. The prognostic reliability of the latter is also better than in the case of C-reactive protein and leukocytes. The application of serial procalcitonin measurements may allow the identification of those septic patients at increased mortality risk, and help improve their treatment. PMID- 22055778 TI - Shortening and tenderness of pre-rigor heated beef: Part 2 - Effect of heating rate on muscles of electrically stimulated carcasses. AB - This study was conducted to compare the effects of rapid and slow heating rates on muscles from electrically stimulated beef carcasses. Myofibrillar and cooking shortening and related changes were measured with physiograph recordings on pre rigor M. triceps brachii strips suspended in paraffin oil during heating. Warner Bratzler shear values were determined on pre-rigor and post-rigor M. triceps brachii samples heated at approximately the same rates at which muscle strips were heated (2 degrees C/2 min and 2 degrees C/12 min), on pre-rigor M. triceps brachii samples heated at 2 degrees C/6 min, 2 degrees C/9 min and 2 degrees C/12 min and on pre-rigor and post-rigor M. triceps brachii and M. longissimus muscle heated similarly at 2 degrees C/12 min. Rapid heating (2 degrees C/2 min) of pre rigor muscle produced more severe myofibrillar shortening that was complete at higher muscle temperature than slow heating (2 degrees C/12 min). Slow heating, in contrast to rapid heating, resulted in a cooked product of lower shear value in both the pre-rigor and post-rigor states. The slower the heating rate of the pre-rigor M. triceps brachii, the more tender was the product. Heating at a rate of 2 degrees C/12 min produced acceptable tenderness in both the pre-rigor M. longissimus and M. triceps brachii muscles but even greater tenderness when both muscles were heated in the post-rigor state. The tenderizing action of severe muscle shortening could not be induced in electrically stimulated muscle. PMID- 22055779 TI - Relationships between chemical composition and physically separated tissues of the pig carcass. AB - Data from the physical and chemical dissection analysis of 50 Large White and 50 Hampshire * Large White carcasses, comprising equal numbers of gilts and castrates, slaughtered at 90 kg liveweight, are presented. The right-hand side of each carcass was dissected into lean, fat and bone and the combined tissues were then minced and chemically analysed for moisture, protein, ether extract and ash. Statistical relationships between the two methods of carcass analysis, except those between bone and ash, were not influenced by sex or breed type. Overall regression equations, i.e. ignoring sex and breed type, for the prediction of percentage lean from moisture, protein and ether extract percentages of the carcasses, had residual standard deviations of 1.26, 1.78 and 1.11, respectively, and corresponding values for the prediction of percentage carcass fat were 1.05, 1.68 and 0.74. Residual standard deviations for predicting percentages of moisture and protein in the carcass from percentage lean content were 1.07 and 0.46 and that for the prediction of percentage ether extract from fat percentage of the carcass was 1.20. Corresponding relationships between bone and ash percentages of the carcass were less satisfactory for predictive purposes. PMID- 22055780 TI - Modification of in-pack conditions to extend the storage life of vacuum packaged lamb. AB - High pH (>5.9) lamb loins from a research abattoir were subjected to differing packaging treatments to determine whether package modification could reliably extend the storage life of chilled lamb cuts beyond that attained by cuts vacuum packaged in film of low gas permeability, as in current commercial practice. Treatments applied were carbon dioxide flushing or addition of a citrate buffer (pH 4.8), a 5% lactic acid solution or a Lactobacillus inoculum (plastic packs only) and packaging in a plastic film of moderately low oxygen permeability (140 cc/m(2)/24 h at 25 degrees C and 90% relative humidity) or in a foil laminate of immeasurably low oxygen permeability. After 12 weeks' storage at -0.5 degrees C, the cuts packaged in the plastic film were spoiled by off-odours produced by enterobacteria, except for inoculated cuts, which, instead, had developed unacceptable dairy flavours. In contrast, cuts packaged in foil laminate developed floras of lactobacilli that had not caused spoilage after 12 weeks, and meat colour was much improved by the exclusion of oxygen. Loin cuts from a commercial packaging operation were packaged in a shrinkable plastic film of low oxygen permeability (30 to 40 cc/m(2)/24 h at 25 degrees C and 90% relative humidity), in foil laminate, or in foil laminate after the addition of 5% lactic acid solution. For the first 6 weeks, cuts were stored in a commercial chiller nominally operating at 0 degrees C; subsequently, they were held in a laboratory chiller at -0.5 degrees C. Some cuts packaged in the shrinkable plastic were spoiled after 9 weeks' storage and all were spoiled at 12 weeks, because of off flavours produced by enterobacteria. All cuts packaged in the foil laminate were very acceptable at 9 weeks but most were spoiled by off-flavours at 12 weeks. Most cuts treated with lactic acid and packaged in foil laminate were unspoiled after 12 weeks. The packaging requirements indicated to be necessary for reliable extension of the storage life of vacuum packaged lamb are discussed. PMID- 22055782 TI - The additional costs of segregated transport to slaughter to decrease Salmonella prevalence in pork--a simulation study. AB - A stochastic simulation model was used to assess the additional costs related to segregated transport to slaughter. This control measure was assumed to be implemented within a producers' association to decrease Salmonella prevalence in pork. Calculations were based on the additional shipments caused by the separate transport of low- and high-prevalence herds and on the additional transport distance caused by changed routing. The results showed that there is not necessarily a considerable increase in the number of shipments due to herd status separation for transport. The percentage of shipments changed due to segregated transport varied between 43% and 69% depending on the threshold prevalence. The additional costs per slaughtered pig varied between 0.07?/pig and 0.58?/pig under the given assumptions. Costs were governed by the percentage of changed shipments and the additional distance of a changed shipment. Due to the fact that the percentage of changed shipments is related to the distribution of herd prevalence within the producers' association, there is no cost-effective threshold in general. Different producers' associations incur different costs caused by segregated transport to slaughter at the same threshold prevalence. The current study supports producers' associations in evaluating the additional costs of segregated transport for their members. PMID- 22055783 TI - The NATF CORNER. PMID- 22055784 TI - Post-mortem metabolism in fresh porcine, ovine and frozen bovine muscle. AB - Post-mortem metabolism was followed by phosphorus-31-NMR in muscle samples obtained from freshly slaughtered pigs and lambs. Resonances for creatine phosphate (CP), ATP, inorganic phosphate (Pi) and sugar phosphates (SP) could be discerned and the intracellular pH could be determined from the spectra. The rates of post-mortem metabolism varied in the following fashion: porcine muscle > ovine muscle > bovine muscle. However, the course of post-mortem metabolism was, in all cases, the same. CP disappeared first and then ATP. Simultaneously, Pi increased, while SP remained relatively constant. The intracellular pH decreased to pH 5.5 in all tissues. In a separate set of experiments the post-mortem metabolism during thawing was studied in bovine muscles that had been frozen immediately after slaughter. Again, the same course of post-mortem metabolism was observed, but the thaw shortening was accompanied by an extremely rapid post mortem metabolism, which was more than ten times as fast as that measured for fresh bovine muscles. The intracellular pH decreased from 7.2 to 5.5 in 45 min. This rapid metabolism started only after the sample ha reached 0 degrees C. Resonances for metabolites were broadened in frozen muscles due to the limited motions that are allowed within the ice lattice. PMID- 22055785 TI - Changes in the chemical composition of rabbit meat during growth. AB - Relative growth rates of water, fat and protein by means of the allometric equation and changes in chemical composition of total meat, meat from hind leg and M. longissimus lumbaris from 1 to 20 weeks of age were studied in 320 rabbits of two strains (New Zealand White and California) and both sexes. All the chemical components showed changes in their allometric coefficients which determined variations in their relative percentages (P < 0.001) during the experimental period. Protein was characterized by a positive allometry although its rate of deposition decreased from 3-4 weeks of age. Water exhibited an important decrease in rate of deposition, passing from positive to negative allometry while, almost simultaneously, the rate of deposition of fat increased, passing from negative to positive allometry; nevertheless, the moment of change of these two components differed among the parts chemically analysed. All these changes were concentrated in a short interval of ages (3-7 weeks of age) that coincided with the one found for anatomic components of the carcass in a previous work (Deltoro & Lopez, 1985). Significant differences (P < 0.001) for mean values were obtained among parts chemically analysed and, to a lesser degree, between lines and sexes. Meat from hind leg and M. longissimus lumbaris had a higher content of protein and a lower content of fat than the rest of the carcass meat. Relating the results to fat-free matter decreased differences but remained significant in most cases and indications of having attained chemical maturity at the end of the experimental period were obtained. PMID- 22055786 TI - Effect of delay time before chilling on toughness in pork with high or low initial pH. AB - Paired M. longissimus dorsi muscles from 56 carcasses of Danish Landrace and Yorkshire breeds, slaughtered at approximately 90 kg live weight, were utilized to study the potential of cold induced toughness in pork. Based upon the pH value 45 min post stunning, the carcasses were divided in two groups: a low (5.7 <= pH < 6.1) and a high one (6.1 <= pH <= 6.5). The effects on Warner-Bratzler shear force, sarcomere length and myofibril fragmentation of inserting a delay time of 0, 2 and 4 h before carcasses entered the chilling tunnel (operating at -28 degrees C to -22 degrees C) were investigated on early excised muscles as well as on muscles removed 30 h post stunning. The left LD muscle from each carcass served as a control while all right sides were used for treatments. pH and temperature measurements obtained from LD muscles left on carcasses during chilling showed that LD muscles belonging to the high pH group involve a risk of cold shortening even when a 2 h delay was used before passing in to the chilling tunnel. Comparing pH groups, however, sarcomere lengths did not differ in control sides whereas the Warner-Bratzler shear force values were significantly higher in LD muscles taken from the high pH group. Early excision of the LD muscle resulted in shorter sarcomere lengths and increased WB shear force only for carcasses belonging to the high pH group, which, however, could be avoided by introducing a 4 h delay time before rapid chilling. The effect of delay time on tenderness from muscles excised from the carcass 30 h post stunning was much less but a 4 h delay did significantly (P < 0.05) improve tenderness in carcasses with high initial pH. Coefficient of correlation between Warner-Bratzler shear force and sarcomere length was -0.12 and nonsignificant in the low pH group, whereas it was -0.57 and highly significant in the high pH group. PMID- 22055787 TI - Clinical biochemistry and pathology of mature beef cattle following ante-mortem intravenous administration of a commercial papain preparation. AB - Ten healthy beef cattle in a commercial abbatoir were treated intravenously before slaughter with a commercial papain-based tenderising injection (Pro Ten). Animals were observed for behavioural and clinical abnormalities following treatment. Serum enzyme activities were measured pre-treatment and post-treatment immediately pre-slaughter < 6 min later to detect liver and muscle damage. Carcases were examined grossly post mortem. Histological examination of liver, kidney and muscle followed. Nine contemporary, age-matched controls were similarly examined. It was concluded that ProTen treatment did not cause any detectable hepatocellular or renal damage and there was no significant difference in the parameters examined between treated and untreated cattle. A decision to ban the use of ProTen in cattle could not therefore be based on the premise that it interfered with the animal's welfare in the period following injection under the conditions pertaining in this experiment. PMID- 22055788 TI - Accelerated production of dry cured hams. AB - Ten uncured legs from the right side of the sampled pork carcasses (Study A) were vacuum tumbled with the cure adjuncts for 30 min (T) and 10 counterparts from the left side were tumbled 30 min, rested 30 min and tumbled an additional 30 min (TRT). Evaluations were conducted at 40 and 70 days after cure application for color, taste attributes, percentage moisture, percentage salt and NO(3)(-) and NO(2)(-) content. Study B was the same except that 18 legs were boned, tumbled and cured for 40, 56 and 70 days. The TRT samples (Study A) at 40 days sustained less color fading (P < 0.05) during cookery, but no differences (P > 0.05) existed among the uncooked hams. Increased cure time enhanced moisture loss and salt content (Study A) and color retention during cookery (Study B). The TRT samples had increased moisture loss and salt content (Study A). PMID- 22055789 TI - Effects of 2-Hz and 60-Hz electrical stimulation on the microstructure of beef. AB - A comparative electron-microscope study was made of the structural changes brought about in bovine longissimus dorsi muscle by 2-Hz and 60-Hz electrical stimulation. Apart from the frequency difference, the two treatments were identical: 500V AC, 600 pulses (2Hz * 300s and 60 Hz * 10 s), and a time of application of about 40 min post mortem. The low-frequency current produced no detectable tissue disruption or irregularity in sarcomere length, whereas the 60 Hz treatment caused widespread supercontraction and the formation of contraction nodes; many sarcomeres in the internodal zones were stretched or fractured. The observations confirm and extend those of our earlier light-microscope study, and support the view that fiber disruption contributes significantly to the tenderizing effect of high-voltage electrical stimulation. PMID- 22055790 TI - Determination of the extent of heat treatment in canned hams by use of the phosphatase test. AB - In determining the core temperature in canned hams by Lind's phosphatase test, residual activity depends, in general, on the integral heat treatment of the core. The concept of heat treatment equivalent is a clearer description of the phenomenon. The heat treatment equivalents were determined at constant temperatures to give a residual activity as proposed by Lind (69 degrees C for 12 lb cans): T versus log t(69) gives a linear relationship with a z value of 5.85 degrees C allowing the classical F(0) and z concept to be used. PMID- 22055791 TI - Foodborne microorganisms and their toxins: Developing methodology (IFT Basic Symposium Series.) Edited by Mark D. Pierson and Norman J. Stern. Marcel Dekker Inc., New York. 1986. Price: US$75. PMID- 22055793 TI - Self-medication or social learning? A comparison of models to predict early adolescent drinking. AB - The current study examined the effects of social anxiety, depressive symptoms, and alcohol expectancies of social behavior change on alcohol involvement to determine whether the self-medication and/or social learning models predicted drinking behavior in a sample of over 400 eighth grade students. Middle school students completed confidential surveys that assessed current alcohol use and expectancies as well as negative affectivity including social anxiety and depressive symptoms. Consistent with the self-medication hypothesis, depressive symptoms predicted more frequent and heavier alcohol use as well as solitary drinking. The social learning model was supported by a negative association between social anxiety and quantity/frequency of drinking and less drinking at parties, and a positive association between alcohol expectancies and all drinking outcomes. Additionally, social anxiety moderated the association between expectancies and alcohol use. These findings suggest that self-medication and social learning processes may both play a role in predicting early adolescent alcohol use and the contexts in which youths drink. PMID- 22055794 TI - Fissures segmentation using surface features: content-based retrieval for mammographic mass using ensemble classifier. AB - RATIONALE AND OBJECTIVES: Accurate classification is critical in mammography computer-aided diagnosis using content-based image retrieval approaches (CBIR CAD). The objectives of this study were to: 1) develop an accurate ensemble classifier based on domain knowledge and a robust feature selection method for CBIR CAD; 2) propose three new features; and 3) assess the performance of the proposed method and new features by using a relatively large imaging data set. MATERIALS AND METHODS: The data set used in this study consisted of 2114 regions of interest (ROI) extracted from a publicly available image database. The proposed ensemble classifier method we called E-DGA-KNN included four steps. In the first step, 804 ROIs depict masses were divided into five classes according to their boundary types. Then, each class of ROI with an equal number of negative ROIs were put together to create a sub-database. Second, a dual-stage genetic algorithm, which was called DGA, was applied on those five sub-databases for feature selection and weights determination respectively. In the third step, five base K-nearest neighbor (KNN) classifiers were created by using the results of the second step on 2114 ROIs, and five detection scores for a given queried ROI were obtained. Finally, these classifiers are combined to yield a final classification. The performances of the proposed methods were evaluated by using receiver operating characteristic (ROC) analysis. A comparison with eight different methods on the data set was provided which include the stepwise linear discriminative analysis algorithm (SLDA) and particle swarm optimization (PSO) algorithm with KNN classifier. RESULTS: When four hybrid feature selection methods were applied with single KNN classifier (ie, DGA-KNN, SLDA-WGA-KNN, SLDA PSO-KNN, GA-PSO-KNN) and the proposed E-DGA-KNN method to the data set, the computed areas under the ROC curve (Az) were 0.8782 +/- 0.0080, 0.8675 +/- 0.0081, 0.8623 +/- 0.0083, 0.8725 +/- 0.0079, and 0.8927 +/- 0.0073, respectively. If all features and single KNN classifier were used, the Az value was 0.8478 +/- 0.0088. Az values were 0.8592 +/- 0.0083 and 0.8632 +/- 0.0081 when SLDA or GA algorithm used alone. CONCLUSIONS: In this study, an ensemble classifier based on domain knowledge and a dual-stage feature selection method was proposed. Evaluation results indicated that the proposed method achieved largest value of ROC compared to other algorithms. The proposed method shows better performance and has the potential to improve the performance of CBIR CAD in interpreting and analyzing mammograms. PMID- 22055795 TI - A meta-analysis of 64-section coronary CT angiography findings for predicting 30 day major adverse cardiac events in patients presenting with symptoms suggestive of acute coronary syndrome. AB - RATIONALE AND OBJECTIVES: To determine the accuracy of 64-section coronary computed tomography angiography (CCTA) in predicting 30 day major adverse cardiac events (MACE) for patients presenting with symptoms concerning for acute coronary syndrome (ACS). MATERIALS AND METHODS: Electronic databases between January 1, 2005, and May, 1, 2011, and reference lists from relevant published research articles were searched. We included studies on adult patients who presented with active symptoms suggestive of ACS, had immediate 64-section CCTA performed and were assessed for MACE at a minimum of 30 days past their initial presentation. Studies had to report or provide sufficient detail to determine sensitivity, specificity, positive predictive value, and negative predictive value in relation to MACE using a 50% diameter stenosis as cutoff criterion for coronary artery disease. RESULTS: Nine studies were included for a total of 1559 patients studied (42.3% women, mean age 51.9 +/- 10.6). Patients ranged from low to intermediate risk for ACS. All had initial inconclusive electrocardiograms and negative cardiac biomarker results. A total of 14.8% of patients had a positive CCTA result. The pooled sensitivity was 93.3% (95% CI 88.3%-96.6%), specificity was 89.9% (95% CI 88.3%-91.3%), positive predictive value was 48.1% (95% CI 42.5% 53.8%), and negative predictive value was 99.3% (95% CI 98.7%-99.6%). CONCLUSION: Sixty-four section CCTA had a 99.3% negative predictive value in excluding MACE for 30 days after initial symptom presentation in 85.2% of our study population. Although the value of 64-section CCTA is best for identifying patients who can safely be discharged home, it is less useful for patients who have positive results. PMID- 22055796 TI - Different algorithms for quantitative analysis of myocardial infarction with DE MRI: comparison with autopsy specimen measurements. AB - RATIONALE AND OBJECTIVES: To compare two semiautomated methods for measurement of infarcted myocardium area on delayed contrast enhanced magnetic resonance imaging, with histopathology findings as standard of reference. MATERIALS AND METHODS: Percentage area of myocardial infarction was measured in 10 Yorkshire landrace pigs manually and using two semiautomated methods. The first (standard deviation method) used two operator-selected regions of interest (ROIs) and nine different cutoff values (one to nine times the standard deviation of signal intensity in normal myocardium) to identify infarction. The second (threshold method) used threshold values based on percentages of maximum signal intensity to identify infarction. Results were compared with histopathology findings. RESULTS: Difference between percentage area of infarction obtained with standard deviation method and autopsy specimens was in the range: -13.5% to +13.2%. With threshold method (thresholds from 30% to 90% of signal intensity), difference was -15% to +23%. Manual contouring underestimated infarcted area by 2% comparing to autopsy results. The best agreement between histopathology and semi-automated software was achieved for 4 standard deviations with standard deviation method: difference -0.45%, and for a percentage threshold of 70% (difference +0.67%) with threshold method. However, with standard deviation method, there was statistically significant difference between ROIs based on their location in viable myocardium: mean difference 1.7 +/- 4%, P < .0001. CONCLUSION: Semiautomated measurement of myocardial infarcted area on delayed enhanced magnetic resonance images performs well compared to autopsy. The threshold method, based on percentages of maximum signal intensity is preferable over standard deviation method, which is more susceptible to variability from location of ROIs within viable myocardium. PMID- 22055797 TI - Semiparametric estimation of the relationship between ROC operating points and the test-result scale: application to the proper binormal model. AB - RATIONALE AND OBJECTIVES: Semiparametric methods provide smooth and continuous receiver operating characteristic (ROC) curve fits to ordinal test results and require only that the data follow some unknown monotonic transformation of the model's assumed distributions. The quantitative relationship between cutoff settings or individual test-result values on the data scale and points on the estimated ROC curve is lost in this procedure, however. To recover that relationship in a principled way, we propose a new algorithm for "proper" ROC curves and illustrate it by use of the proper binormal model. MATERIALS AND METHODS: Several authors have proposed the use of multinomial distributions to fit semiparametric ROC curves by maximum-likelihood estimation. The resulting approach requires nuisance parameters that specify interval probabilities associated with the data, which are used subsequently as a basis for estimating values of the curve parameters of primary interest. In the method described here, we employ those "nuisance" parameters to recover the relationship between any ordinal test-result scale and true-positive fraction, false-positive fraction, and likelihood ratio. Computer simulations based on the proper binormal model were used to evaluate our approach in estimating those relationships and to assess the coverage of its confidence intervals for realistically sized datasets. RESULTS: In our simulations, the method reliably estimated simple relationships between test-result values and the several ROC quantities. CONCLUSION: The proposed approach provides an effective and reliable semiparametric method with which to estimate the relationship between cutoff settings or individual test result values and corresponding points on the ROC curve. PMID- 22055798 TI - Positron emission tomography of human hepatocellular carcinoma xenografts in mice using copper (II)-64 chloride as a tracer with copper (II)-64 chloride. AB - RATIONALE AND OBJECTIVES: The aim of this study was to assess copper metabolism of human hepatocellular carcinoma (HCC) with positron emission tomographic (PET) imaging using copper (II)-64 chloride ((64)CuCl(2)) as a tracer. MATERIALS AND METHODS: PET imaging of athymic mice (n = 5) bearing extrahepatic HCC xenografts was performed 24 hours after the intravenous injection of (64)CuCl(2), followed by ex vivo tissue radioactivity assay. Expression of human copper transporter 1 (hCTR1) in HCC cells and tissues was examined by real-time reverse transcription polymerase chain reaction and immunohistochemistry analysis, respectively. RESULTS: The extrahepatic HCC xenografts in mice with increased uptake of (64)Cu radionuclide were visualized on the micro-PET images obtained 24 hours after the intravenous injection of (64)CuCl(2). PET quantitative analysis revealed increased (64)Cu radioactivity in tumor tissues (2.7 +/- 0.6 %ID/g) compared to that in the soft tissue of the left shoulder opposite to the tumor site (0.6 +/- 0.2 %ID/g) and the brain (0.7 +/- 0.1 %ID/g) but lower than that of the liver (16.6 +/- 1.3 %ID/g). Expression of hCTR1 in the HCC cells and xenograft tumor tissues was demonstrated by real-time reverse transcription polymerase chain reaction and immunohistochemistry analysis, respectively. The expression level of hCTR1 in the Hep3B HCC xenograft tissues was lower than that detected in the normal hepatic tissues and the tissue samples of well-differentiated primary HCC. Variable expression of hCTR1 was detected in the tissue samples of moderately differentiated primary HCC. CONCLUSIONS: Extrahepatic human HCC xenografts in mice could be localized with (64)CuCl(2) PET imaging, which might be useful for the localization and quantitative assessment of copper metabolism in extrahepatic metastases of HCC in humans. PMID- 22055799 TI - Non-invasive quantification of triglyceride content in steatotic rat livers by (1)H-MRS: when water meets (too much) fat. AB - RATIONALE AND OBJECTIVES: The aims of this study were to explore the relationship between triglyceride (TG) and water in steatotic rat livers and to accordingly test the validity of the currently used steatosis calculation methods from magnetic resonance spectra. The approximations commonly used to derive steatosis degrees from magnetic resonance spectra include the generic types TG/water and TG/(TG + water). MATERIALS AND METHODS: Hepatic fat and water content was quantitated by histology, magnetic resonance spectroscopy (MRS), gas chromatography, and dry/wet weight ratio analysis in increasingly (0%-95%) steatotic rats. Correlation analysis was performed to assess the statistical relationships among the steatosis quantification techniques. Subsequently, data were fitted with linear and nonlinear functions to determine the relationship between hepatic water fraction versus hepatic TG content and TG/water ratio versus macrovesicular steatosis degree to test the validity of commonly used steatosis calculation methods. RESULTS: Histologic analysis of macrovesicular steatosis correlated very strongly with TG content determined by gas chromatography and MRS. A strong positive correlation was also found between gas chromatography-derived and MRS-derived TG content. Biochemical analysis revealed a linear converse relationship between hepatic fat and water content. This relationship was nonlinear when determined by MRS. The MRS-based TG/(TG + water) type approximations reflected the linear water-fat relationship better than the TG/water-type approximations, particularly when the calculations were performed with a maximum number of TG resonances. CONCLUSIONS: Hepatic fat approximations of the type TG/water overestimate hepatic steatosis degree because hepatic fat accumulation concurs with hepatic water exudation. Consequently, MRS-based approximations should be of the type TG/(TG + water) and contain a maximum number of TG resonances in the denominator. PMID- 22055800 TI - A report on the current status of grand rounds in radiology residency programs in the United States. AB - RATIONALE AND OBJECTIVES: A national needs assessment of radiology program directors was performed to characterize grand rounds (GR) programs, assess the perceived educational value of GR programs, and determine the impact of the recent economic downturn on GR. MATERIALS AND METHODS: A 28-question survey was developed querying the organizational logistics of GR programs, types of speakers, content of talks, honoraria, types of speakers invited, response to the economic downturn, types of speaker interaction with residents, and perceived educational value of GR. Questions were in multiple-choice, yes-or-no, and five point Likert-type formats. The survey was distributed to the program directors of all radiology residencies within the United States. RESULTS: Fifty-seven of 163 programs responded, resulting in a response rate of 36%. Thirty-eight programs (67%) were university residencies and 10 (18%) were university affiliated. Eighty two percent of university and 60% of university-affiliated residencies had their own GR programs, while only 14% of community and no military residencies held GR. GR were held weekly in 18% of programs, biweekly in 8%, monthly in 42%, bimonthly in 16%, and less frequently than every 2 months in 16%. All 38 programs hosting GR reported a broad spectrum of presentations, including talks on medical education (66%), clinical and evidence-based medicine (55%), professionalism (45%), ethics (45%), quality assurance (34%), global health (26%), and resident presentations (26%). All programs invited speakers from outside the institution, but there was variability with regard to the frequency of visits and whether invited speakers were from out of town. As a result of recent economic events, one radiology residency (3%) completely canceled its GR program. Others decreased the number of speakers from outside their cities (40%) or decreased the number of speakers from within their own cities (16%). Honoraria were paid to speakers by 95% of responding programs. Most program directors (79%) who had their own GR programs either strongly agreed or agreed that GR are an essential component of any academic radiology department, and this opinion was shared by a majority of all respondents (68%). Almost all respondents (97%) either strongly agreed or agreed that general radiologic education of imaging subspecialists is valuable in an academic radiology department. A majority (65%) either strongly agreed or agreed that attendance at GR should be expected of all attending radiologists. CONCLUSIONS: GR programs among radiology residencies tend to have similar formats involving invited speakers, although the frequency, types of talks, and honoraria may vary slightly. Most programs value GR, and all programs integrate GR within resident education to some degree. The recent economic downturn has led to a decrease in the number of invited visiting speakers but not to a decrease in the amounts of honoraria. PMID- 22055801 TI - New AIRP. PMID- 22055802 TI - The effect of anti-tubercular drug, ethionamide on the secondary structure of serum albumins: a biophysical study. AB - Serum albumin (SA) is the principal extra cellular protein with higher concentration in the blood plasma and acts as a carrier for many drugs to different molecular targets. The present work is designed to investigate the mechanism of interaction between the protein and an anti-tubercular drug, ethionamide (ETH) at the physiological pH by different molecular spectroscopic techniques viz., fluorescence, UV absorption, CD and FTIR. The interaction of SA with ETH was studied by following the quenching of intrinsic fluorescence of protein by ETH at different temperatures. The Stern-Volmer quenching constant, binding constant and the binding site numbers were calculated from fluorescence results. The results indicated the presence of static quenching mechanism in both HSA-ETH and BSA-ETH systems. The distances of separation between the acceptor and donor were calculated based on the theory of fluorescence resonance energy transfer and were found to be 2.35 nm and 2.18 nm for HSA-ETH and BSA-ETH systems, respectively. The conformational changes in protein were confirmed from UV absorption, CD and FTIR spectral data. Displacement experiments with different site probes revealed that the site I was the main binding site for ETH in protein. Effect of some metal ions was also investigated. PMID- 22055803 TI - Seizure in a diabetic patient. Hypoglycemia or a side effect of continuous glucose monitoring? PMID- 22055804 TI - Effects of high pressure treatment of rabbit Longissimus dorsi muscles on the microsomal membranes. AB - High pressure treatment (150 MPa for 10 min at 35 degrees C) of rabbit longissimus dorsi muscles reduced the yield of a heavy microsomal preparation (8000-28 000 g) by approximately 90%. This was shown to be due to the loss of the sarcoplasmic reticulum, the major component of microsomal preparations, from untreated muscles. While microsomal preparations from pressure-treated muscles were shown to have lost all of their (Ca(2+), Mg(2+))-ATPase activity they retained all their Mg(2+)-ATPase (basal) activity. Sucrose density gradient centrifugation of these preparations yielded two fractions. By reason of its low density, high cholesterol content, high Mg(2+)-ATPase activity, SDS-gel protein profile and solubility in lysolecithin, the lightest fraction appeared to be derived from the transvers tubules. The heavier fraction, present in greater quantity but with a lower Mg(2+)-ATPase activity than the light fraction, was probably derived from the sarcolemma. PMID- 22055805 TI - Measurement of effective diffusivities of ionic and non-ionic solutes through beef and pork muscles using a diffusion cell. AB - A diffusion cell in conjunction with a new mathematical model was used to measure the apparent diffusion coefficients of sodium chloride, potassium nitrate and glucose through beef semitendinosus and pork longissimus dorsi muscles. The apparent diffusion coefficient was obtained within less than 180 min with a coefficient of variation less than 10% in most cases. The influence of temperature can be adequately explained by the Arrhenius-type law with activation energy between 19 and 26 kJ/mol depending on the diffusant. However, these values were not significantly different. Finally, we showed that the apparent diffusion coefficient of sodium chloride is not affected by the direction of the muscle fibre to the axes of diffusion while glucose diffusion parallel to the muscle fibre can be three times greater than diffusion at a right angle to the muscle fibre. PMID- 22055806 TI - Influence of porcine stress on blood composition and early post-mortem meat quality in pigs of different halothane genotypes. AB - The purpose of this study was to investigate porcine stress, blood serum values and early post-mortem (pm) meat quality in pigs of unknown and known halothane genotype. Collection, transportation and slaughtering of the pigs were studied from the farm up to the carcass chilling (45 min pm). Reactors (nn) had the highest creative kinase (CK) activity. CK activity increased most prominently during transport in reactors, and at the abattoir in non-reactors (Nn or NN). The content of serum glucose was highest in non-reactors and lowest in non-carriers (NN, P<0.01). Serum glycerol level was highest in reactors and lowest in carriers (Nn, P < 0.05). Differences in serum lactate and pH values were not significant. Carriers had the highest and non-reactors the lowest carcass temperature, 0 min pm (P = 0.001). Temperature of non-reactors increased most rapidly (9.4%) and that of carriers increased most slowly (0.9%) during scalding. Reactors had the most rapid (3.1%) and carriers the slowest (0.3%) fall in carcass temperature between scalding and chilling. No significant differences were found between halothane genotypes in the rate of glycogen breakdown and lactate formation, 45 min pm. PSE (pH(1) <= 5.8) frequencies of reactors, non-reactors, non-carriers and carriers were 100.0, 14.3, 13.0 and 12.5, respectively. PMID- 22055807 TI - Use of haemoglobin in foods-A review. AB - Blood from domestic meat animals contains biologically valuable protein equivalent to 6-7% of the lean meat content in the carcass. The major part of the protein is haemoglobin in the erythrocytes which even in minute concentrations imparts a dark brownish colour to foods. Large scale use of haemoglobin in foods consequently requires that the protein is made colourless unless attempts are made to hide the colour by technological manipulation in processing. The haem pigment can be removed from the globin by extraction with acidified organic solvents, usually acetone, or absorption on certain agents like carboxymethylcellulose. Alternatively, the globin may be digested by proteolytic enzymes and the liberated amino acids separated from the haem by ultrafiltration or centrifugation. Another approach is oxidative destruction of the haem after inactivation of the catalase activity of the erythrocytes. Hydrogen peroxide is preferred as oxidative agent but care must be taken to limit its impairment of protein quality. Because of its high lysine content globin should be suitable for fortification of cereals. Together with the blood plasma globin it may be used to replace meat in cured meat products. Use of blood proteins in foods may, however, sometimes be opposed for psychological reasons. PMID- 22055808 TI - Mineral composition of lamb carcasses from the United States and New Zealand. AB - The mineral composition-iron (Fe), zinc (Zn), copper (Cu), calcium (Ca), magnesium (Mg), sodium (Na), potassium (K), fluoride (F), and phosphorus (P) (New Zealand lamb only)-of lean tissue from lamb retail cuts was studied. Twenty-four US lamb carcasses of different ages (5 to 11 months), geographical regions (Texas, Colorado and Montana) and USDA quality grades (Prime and Choice) and 27 New Zealand lamb carcasses from three weight groups (11 to 12.5 kg, 13 to 14.5 kg, and 16.5 to 18 kg), age rangining from 7 to 8 months, were selected for use in this study. Mineral concentrations were influenced more by retail cut and age than by quality grade or weigth group. Foreshank and shoulder cuts from both the US and New Zealand group consistently had the highest (P < 0.05) Zn content among the cuts. The K content of the muscle in US lambs increased as age increased, while the level of Ca and Zn in New Zealand lambs decreased as carcass weight increased. Except for Ca, the mineral concentrations of the lean tissue from US lambs were higher than the New Zealand lambs, although the differences were not always significant. US lambs had approximately 20%, 30% and 37% more Fe, Zn and Mg, respectively, but 27% less Ca than lean tissue from the New Zealand lambs. PMID- 22055809 TI - Effects of pork muscle quality on bacterial growth and retail case life. AB - The effects of muscle quality (PSE, normal, DFD) upon the bacteriology and retail case life of pork chops were determined. Pork loin chops were processed from boneless backs after 90 days of frozen storage at -30 degrees C. Variation in bacterial numbers was due to a highly significant (p < 0.001) storage time by muscle quality interaction. During simulated retail display, total psychrotrophs, Pseudomonas spp., Brochothrix thermosphacta and Enterobacteriaceae were lowest on PSE pork and highest on DFD pork in comparison to normal pork. Differences in bacterial densities were due to a longer lag phase in PSE pork and a shorter lag phase in DFD pork than in normal pork. Of the three muscle quality groups, DFD was most susceptible to the development of spoilage odours, while PSE pork was most sensitive to deterioration in appearance. PMID- 22055810 TI - An improved procedure for identifying fiber types in ovine muscles. AB - An improved histochemical procedure has been developed for the identification of three muscle fiber types (betaR, alphaR, alphaW) in two ovine muscles. This procedure can be used in lieu of the traditional reciprocal procedures of using an oxidative enzyme and ATPase to identify fiber types. The advantage of this simultaneous staining procedure is that it eliminates duplication of effort and time plus it distinguishes the alphaR (intermediate) fibers more clearly than the traditional methods. For best results, muscle samples must be evaluated within 2h of slaughtering the animal and care must be taken to monitor the pH at regular intervals. More research is needed to determine specific conditions, i.e. sample time, pH, enzyme activity, etc., before this method can be recommended as the most appropriate procedure for determining fiber type in muscles of other species. PMID- 22055811 TI - Differences in quality characteristics of normal, PSE and DFD pork. AB - Differences in water-holding capacity, colour and tenderness/toughness were studied in 21 pork loins belonging to three quality categories, i.e. dark firm dry (DFD), normal and pale soft exudative (PSE). The division into the three groups was based upon the ultimate pH-values of the loins (< pH 5.5, pH 5.5-6.0, pH > 6.4). The PSE loins were characterized by a poor waterholding capacity, higher cooking loss and paler colour in contrast to the DFD category. The normal loins took an intermediate position. Neither sarcomere length, determined on fresh muscle tissue, nor Armour tenderometer values showed significant differences between the various quality categories. This was in contrast to the Warner-Bratzler (W-B) shear force values, determined on cooked loins, which had the lowest values in the DFD category. A strong relationship between the W-B values and the cooking losses was found. It was concluded that neither sarcomere length nor Armour tenderometer measurements were able to predict the shear force values of cooked pork loins. PMID- 22055812 TI - Carbohydrate-conjugate heterobimetallic complexes: synthesis, DNA binding studies, artificial nuclease activity and in vitro cytotoxicity. AB - New carbohydrate-conjugated heterobimetallic complexes [C(32)H(62)N(10)O(8)NiSn(2)Cl(4)]Cl(2)(1) and [C(32)H(62)N(10)O(8)CuSn(2)Cl(4)]Cl(2) (2) were synthesized and characterized by spectroscopic (IR, (1)H, (13)C, and (119)Sn NMR, EPR, UV-vis, ESI-MS) and analytical methods. The interaction studies of 2 with CT DNA were studied by using various biophysical techniques, which showed high binding affinity of 2 toward CT DNA. The extent of interaction was further confirmed by the interaction of 2 with the nucleotides viz.; 5'-AMP, 5'-CMP, 5'-GMP, and 5'-TMP, by absorption titration. (1)H, (31)P, (119)Sn NMR spectroscopy further validated the interaction mode of 2 with 5'-GMP. The electrophoresis pattern observed for 2 with supercoiled pBR322 DNA, exhibited significantly good nuclease activity following oxidative pathway. The preferential selectivity of 2 toward the major groove was observed on interaction of 2 with pBR322 DNA, in the presence of standard groove binders viz.; DAPI and methyl green. Additionally, in vitro antitumor activity of 2 was evaluated on a panel of human cancer cell lines, exhibiting remarkable cytotoxicity activity against Colo205 (colon) and MCF7 (breast) cell lines with GI(50) values <10 MUg/mL. PMID- 22055813 TI - Green microwave-assisted synthesis of cellulose/calcium silicate nanocomposites in ionic liquids and recycled ionic liquids. AB - Fabrication of biomass materials by a microwave-assisted method in ionic liquids allows the high value-added applications of biomass by combining three major green chemistry principles: using environmentally preferable solvents, using an environmentally friendly method, and making use of renewable biomass materials. Herein, we report a rapid and green microwave-assisted method for the synthesis of the cellulose/calcium silicate nanocomposites in ionic liquids and recycled ionic liquids. These calcium silicate nanoparticles or nanosheets as prepared were homogeneously dispersed in the cellulose matrix. The experimental results confirm that the ionic liquids can be used repeatedly. Of course, the slight differences were also observed using ionic liquids and recycled ionic liquids. Compared with other conventional methods, the rapid, green, and environmentally friendly microwave-assisted method in ionic liquids opens a new window to the high value-added applications of biomass. PMID- 22055814 TI - Preparation and characterization of new and improved soluble-starches, -amylose, and -amylopectin by reaction with benzaldehyde/zinc chloride. AB - Seven different starches from potato, rice, maize, waxymaize, amylomaize-VII, shoti, and tapioca, and potato amylose and potato amylopectin have been reacted with benzaldehyde, catalyzed by ZnCl(2), to give new water-soluble starches and water soluble-amylose and soluble-amylopectin. In contrast to the native starches, aqueous solutions of the modified starches could not be precipitated with 2-, 3-, or 4-volumes of ethanol. beta-Amylase gave no reaction with the modified starches, in contrast to the native starches, indicating that the modification occurred exclusively at the nonreducing-ends, giving 4,6-benzylidene D-glucopyranose at the nonreducing-ends. Reactions of alpha-amylase with native and modified potato and rice starches gave a decrease in the triiodide blue color and an increase in the reducing-value that were similar for the native- and modified-starches, indicating the modified starches had not been significantly altered by the modification. The benzaldehyde-modified starches and benzaldehyde modified potato amylose and potato amylopectin components, therefore, have a starch structure very much like their native counterparts, in contrast to the Lintner, Small, and the alcohol/acid-hydrolyzed soluble-starches that have undergone acid hydrolysis. The benzaldehyde-modified starches and starch components have significantly higher water solubility than their native counterparts even though the structures of the modified starches had only been slightly altered from the structures of their native counterparts. They all gave crystal-clear solutions that did not retrograde. PMID- 22055815 TI - Green synthesis of xylan hemicellulose esters. AB - The esterification of xylan type hemicelluloses, isolated from birchwood, was carried out firstly in homogeneous conditions using N,N-dimethylformamide (DMF) and lithium chloride (LiCl) in the presence of 4-dimethylaminipyridine (DMAP). The degree of substitution (DS) of xylan acetates ranged between 0.9 and 2.0 as a function of experimental conditions. Due to the problems of toxicity and recycling of DMF, an alternative method of esterification is reported in the second part of this work, performing in the absence of organic solvent and using DMAP or methanesulfonic acid (MSA) as catalysts. Acetylation reaction catalyzed by MSA was developed through an experimental design in order to achieve the highest DS under the mildest conditions. The significant factors and their interactions were identified. The optimization of reaction parameters allowed to obtain a high DS (1.6) and maximal yield (85%). Moreover, the reactivity of propionic and hexanoic anhydrides was evaluated and hydrophobic xylan esters with low degrees of substitution were obtained. PMID- 22055816 TI - Chemical structure of the complex pyruvylated and sulfated agaran from the red seaweed Palisada flagellifera (Ceramiales, Rhodophyta). AB - A homogeneous agaran fraction from Palisada flagellifera (Laurencia complex, Rhodomelaceae, Ceramiales) was obtained by aqueous room-temperature extraction, followed by ion-exchange chromatography. This galactan presents a highly complex structure with at least 18 different types of derivatives. The A units were found mostly pyruvylated, 2-sulfated (~34%), and 6-methylated (~34%), with the latter partially 2- and 2,4-sulfated. Minor amounts of beta-D-galactopyranosyl units 2-, 6- and 2,6-sulfated, 6-glycosylated, and non-substituted are also present. The B units are L-sugars composed predominantly of their cyclized derivatives, 3,6 anhydrogalactose and 3,6-anhydro-2-O-methylgalactose (~56%). The former are linked to beta-D-galactosyl (6-methyl) (6-glycosylated) units, as well as to 4,6 O-(1-carboxyethylidene)-beta-D-galactose 2-sulfate in the proportion of 3:1.8, respectively. A significant amount (~18%) of the alpha-L-galactopyranosyl units are linked to pyruvylated beta-D-galactose 2-sulfate residues. An important part of the B-units (20%) is represented by alpha-L-galactose 6-sulfate substituted on C-3 by xylosyl, galactosyl and/or 2,3-di-O-methylgalactose units or sulfate groups that preclude their cyclization to 3,6-anhydrogalactosyl derivative. The precursor units are present in relatively low percentages. Kinetic studies suggest that in P. flagellifera agaran the cyclizable units are linked to 6-O methyl-beta-D-galactosyl and/or beta-D-galactosyl units (6-glycosylated). The structural complexity of this polysaccharide is increased by the presence of 2- and 3,6-sulfated alpha-L-galactoses, with the latter additionally 2-O-methylated. Therefore, the major subfraction obtained from the cold extract contains structurally complex sulfated, methylated, and pyruvylated agaran. PMID- 22055817 TI - Investigation of a sulfate transfer during autohydrolysis of a fucoidan from the brown alga Fucus evanescens by tandem ESIMS. AB - A fucoidan from the brown alga Fucus evanescens was effectively depolymerized by autohydrolysis. Negative-ion electrospray ionization mass spectrometry (ESIMS) revealed that the mixture contained sulfated mono- and oligosaccharides with polymerization degree (DP) up to 6, having from 1 to 4 sulfate groups per molecule. The prevalence of oligosaccharides with even DP was observed. It could be explained by the tendency of the 3-linked alpha-L-fucopyranose residues to hydrolyze faster than 4-linked ones. The intermolecular sulfate transfer during autohydrolysis was detected by ESIMS, when equimolar quantities of D-Rib and D Glc were added as acceptors. The products were singly-sulfated and hexose was about four times more effective as an acceptor, than pentose. It was impossible to record MS/MS spectra of the sulfate transfer products, since intensities of their ions were too low. PMID- 22055818 TI - O-Acetyl location on cepacian, the principal exopolysaccharide of Burkholderia cepacia complex bacteria. AB - Cepacian is an exopolysaccharide produced by the majority of the isolates belonging to the Burkholderia cepacia complex bacteria, a group of 17 species, some of which infect cystic fibrosis patients, sometime with fatal outcome. The repeating unit of cepacian consists of a backbone having a trisaccharidic repeating unit with three side chains, as reported in the formula below. The exopolysaccharide is also acetylated, carrying from one to three acetyl esters per repeating unit, depending on the strain examined. The consequences of O acetyl substitution in a polysaccharide are important both for its biological functions and for industrial applications, including the preparation of conjugated vaccines, since O-acetyl groups are important immunogenic determinants. The location of acetyl groups was achieved by NMR spectroscopy and ESI mass spectrometry and revealed that these substituents are scattered in non stoichiometric ratio on many sugar residues in different positions, a feature which adds to the already unique carbohydrate structure of the polysaccharide. PMID- 22055819 TI - Chemical synthesis of polyprenyl sialyl phosphate, a probable biosynthetic intermediate of bacterial polysialic acid. AB - Using reaction of moraprenyl phosphate with the known N-acetylsialyl chloride and the novel N,N-diacetylsialyl (Neu5Ac(2)) chloride alpha- and beta-anomers of polyprenyl sialyl phosphate were synthesized for the first time. The alpha selectivity dramatically increased when Neu5Ac(2) chloride was used as the glycosyl donor. PMID- 22055820 TI - Catalytic dehydration of xylose to furfural: vanadyl pyrophosphate as source of active soluble species. AB - The acid-catalysed, aqueous phase dehydration of xylose (a monosaccharide obtainable from hemicelluloses, e.g., xylan) to furfural was investigated using vanadium phosphates (VPO) as catalysts: the precursors, VOPO(4).2H(2)O, VOHPO(4).0.5H(2)O and VO(H(2)PO(4))(2), and the materials prepared by calcination of these precursors, that is, gamma-VOPO(4), (VO)(2)P(2)O(7) and VO(PO(3))(2), respectively. The VPO precursors were completely soluble in the reaction medium. In contrast, the orthorhombic vanadyl pyrophosphate (VO)(2)P(2)O(7), prepared by calcination of VOHPO(4).0.5H(2)O at 550 degrees C/2 h, could be recycled by simply separating the solid acid from the reaction mixture by centrifugation, and no drop in catalytic activity and furfural yields was observed in consecutive 4 h batch runs (ca. 53% furfural yield, at 170 degrees C). However, detailed catalytic/characterisation studies revealed that the vanadyl pyrophosphate acts as a source of active water-soluble species in this reaction. For a concentration of (VO)(2)P(2)O(7) as low as 5 mM, the catalytic reaction of xylose (ca. 0.67 M xylose in water, and toluene as solvent for the in situ extraction of furfural) gave ca. 56% furfural yield, at 170 degrees C/6 h reaction. PMID- 22055821 TI - Structural and physicochemical characterisation of rye starch. AB - The gelatinisation, pasting and retrogradation properties of three rye starches isolated using a proteinase-based procedure were investigated and compared to those of wheat starch isolated in a comparable way. On an average, the rye starch granules were larger than those of wheat starch. The former had very comparable gelatinisation temperatures and enthalpies, but slightly lower gelatinisation temperatures than wheat starch. Under standardised conditions, they retrograded to a lesser extent than wheat starch. The lower gelatinisation temperatures and tendencies of the rye starches to retrograde originated probably from their higher levels of short amylopectin (AP) chains [degree of polymerisation (DP) 6 12] and their lower levels of longer chains (DP 13-24) than observed for wheat starch. The rapid visco analysis differences in peak and end viscosities between the rye starches as well as between rye and wheat starches were at least partly attributable to differences in the levels of AP short chains and in average amylose molecular weight. The AP average chain lengths and exterior chain lengths were slightly lower for rye starches, while the interior chain lengths were slightly higher than those for wheat starch. PMID- 22055822 TI - Effect of temperature and pH on the post-mortem degradation of myofibrillar proteins. AB - Incubation of bovine muscle at 37 degrees C promoted a more drastic proteolytic change in myofibrillar proteins, as determined from sodium dodecyl sulphate polyacrylamide gels of isolated myofibrils, than incubation at 4 degrees C. Degradation of myosin and troponin-T were the most noticeable changes at 37 degrees C. Loss of alpha-actinin was observed in the 4 degrees C incubated muscle. Ground bovine muscle incubated at pH 5.4 and 7 revealed that alterations in myosin and troponin-T were the most noticeable changes at ph 5.4 while troponin-T and alpha-actinin were altered at pH7. More troponin-T degradation occurred at pH 5.4 and 37 degrees C than at pH7 and 4 degrees C (similar to the degradation of myosin), indicating that troponin-T degradation in post-mortem muscle may be an indicator of overall myofibrillar proteolysis and not responsible for post-mortem tenderisation per se. Myosin degradation in the ground samples incubated at pH 5.4 and in whole samples incubated at 37 degrees C was compared with the digestion of myofibrillar myosin by papain. Both pyrophosphate and Guba-Straub extracts of the 37 degrees C and pH 5.4 treated samples confirmed that myosin degradation did occur to a much greater extent at this temperature and pH than at 4 degrees C and pH7, and, in addition, at pH 5.4 frequent cleavage occurred near the papain sensitive site of myosin. PMID- 22055823 TI - Influence of delayed bleeding on sensory characteristics of beef. AB - Sensory characteristics of bovine longissimus dorsi and biceps femoris muscles from 30 heifers exsanguinated 0, 3 or 6 min after stunning and 36 steers exsanguinated 0, 3 or 30 min after stunning were evaluated to determine if delayed bleeding influenced palatability. More blood was retained in carcasses of animals where exsanguination was delayed after stunning than in control animals, but no consistent differences existed for total pigment or per cent hemoglobin in muscle. Tenderness, juiciness, flavor, shear values and cooking loss were not affected by treatment. PMID- 22055824 TI - Studies on the Criollo goat of Northern Mexico: Part 1 - The effects of body weight on body components and carcass development. AB - Male Criollo castrate goats were reared on natural rangeland and also given some concentrate supplementation. They were slaughtered in groups of ten at 8, 12, 16 and 24 kg live weight. At slaughter the weights of body components were recorded and also carcass measurements and joint weights on the chilled left half of each carcass, which was then completely dissected into lean, fat and bone tissues. With increasing slaughter weight the proportion of internal body components minus gut contents, increased relative to the external components. In some of the goats from the higher slaughter weight groups the gut contents formed up to 26% of the total live weight. The dressing percentage based on empty body weight did not show an appreciable increase with increasing slaughter weight. The lean proportion in the carcass rose from 56% of the carcass weight in the 8 kg group to about 68% in the 24 kg group. The proportion of fat in the carcasses did not show any increase with increasing slaughter weight. The results indicate that, in terms of yield of lean meat and also edible offal, it is better not to slaughter castrate male Criollo goats before 24 kg live weight. PMID- 22055825 TI - Calcium transport by bovine skeletal-muscle mitochondria and its relationship to post-mortem muscle. AB - A study was made of factors thought to affect calcium retention by highly purified skeletal-muscle mitochondria. Substrate-supported (oxygen-dependent) and ATP-supported Ca(2+) uptake were both examined. The effects of high concentrations of inorganic phosphate, inhibition of adenine nucleotide translocation and other influences on ATPase activity were also investigated. Results indicate that calcium is not released during anoxia if ATP is available to the mitochondrial ATPase. The data are discussed in relation to mitochondrial calcium transport in general, and its significance in post-mortem muscle. PMID- 22055826 TI - Meat microbiology (1982) Edited by M. H. Brown. Applied Science Publishers Ltd, London and New York. 529 pp. Price: L46.00. PMID- 22055827 TI - Carcass evaluation in livestock breeding, production and marketing by A.J. Kempster, A. Cuthbertson and G. Harrington. Granada Publishing Ltd, London, Toronto, New York. 1982. Price: L20.00. PMID- 22055828 TI - Microbiology of foods. The ecological essentials of assurance and assessment of safety and quality (3rd edn) By D.A.A. Mossel. The University of Utrecht, The Netherlands. 1982. Price: 52 Dutch Florins. PMID- 22055829 TI - [Dieulafoy's lesion of the gallbladder as a cause of hemobilia with hemoperitoneum]. AB - Dieulafoy's lesion is an uncommon vascular anomaly causing massive gastrointestinal hemorrhage, characterized by bleeding from an arteriole that protrudes through a tiny mucosal defect. Although Dieulafoy's lesion was initially described in the stomach and upper gastrointestinal tract, cases have also been reported in the colon, rectum and anal canal. We report the first case of Dieulafoy's lesion in the gallbladder, which presented as massive peritoneal bleeding. We describe the clinical and pathological characteristics of this unusual entity, as well as the approach to its diagnosis and treatment. PMID- 22055830 TI - Quantification of a novel natural antioxidant (UP302) in rat plasma using ultra high performance liquid chromatography-tandem mass spectrometry. AB - UP302 is a novel natural antioxidant isolated from Dianella ensifolia (Liliaceae). In the investigation, a specific and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry for quantitative determination of UP302 in rat plasma was developed and validated. UP302 and the internal standard daidzein were extracted from 100 MUL aliquots of rat plasma using methanol. Detection of UP302 and IS was done by tandem mass spectrometry, operating in negative ion and selected reaction monitoring acquisition mode. The precursor-product ion transitions monitored for UP302 and daidzein were m/z 301.1 >135.2 and 252.9->132.0, respectively. The linearity of the method was observed within the concentration range of 5-2000 ng/mL. Intra- and inter-day assay variations were less than 15%, and the accuracy values were between 99.2% and 107.3%. The method was successfully applied to stability investigation of UP302 incubated in rat plasma at 37 degrees C and measurement of UP302 in plasma after intravenous administration of UP302 to rats at a single dose of 5 mg/kg. Incubation stability revealed that within first one hour, UP302 was rapidly declined approximately 35% and remained stable after 4 h. Pharmacokinetic values of half-life, volume of distribution, systemic clearance and mean residence time were 0.87 +/- 0.58 h, 6.90 +/- 3.35 L/kg, 5.89 +/- 1.21 L/h kg and 0.34 +/- 0.13 h, respectively. PMID- 22055831 TI - Anion exchange SPE and liquid chromatography-tandem mass spectrometry in GHB analysis. AB - In this study, the extraction of gamma-hydroxybutyrate (GHB) from urine using solid-phase extraction (SPE) is described. SPE was performed on anion exchange columns after samples of urine had been diluted with de-ionized water. After application of the diluted samples containing GHB-d(6) as an internal standard, the sorbent was washed with deionized water and methanol and dried. The GHB was eluted from the SPE column with a solvent consisting of methanol containing 6% glacial acetic acid. The eluent was collected, evaporated to dryness, and dissolved in mobile phase (100 MUL) for analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in negative multiple reaction monitoring (MRM) mode. Liquid chromatography was performed in gradient mode employing a biphenyl column and a mobile phase consisting of acetontitrile (containing 0.1% formic acid) and 0.1% aqueous formic acid. The total run time for each analysis was less than 5 min. The limits of detection/quantification for this method were determined to be 50 and 100 ng/mL, respectively. The method was found to be linear from 500 ng/mL to 10,000 ng/mL (r(2)>0.995). The recovery of GHB was found to be greater than 75%. In this report, results of authentic urine samples analyzed for GHB by this method are presented. GHB concentrations in these samples were found to be range from less than 500 ng/mL to 5110 ng/mL. PMID- 22055832 TI - Analytical characterization and rapid determination of 2 (diphenylmethyl)pyrrolidine in blood and application to an internet product. AB - The increased availability of new psychoactive substances ("legal highs") from retail shops or internet sources has caught the imagination of consumers, law enforcement and scientific communities. The present study describes the identification of 2-(diphenylmethyl)pyrrolidine (DPMP, desoxy-D2PM) as the key constituent found in an internet product called "A3A New Generation". Analytical characterization of this new generation "legal high" product was based on gas chromatography (EI/CI) ion trap mass spectrometry and liquid chromatography (HPLC) using electrospray ionization tandem mass spectrometry and diode array detection. A quantitative method was also developed and validated for the detection of DPMP in human whole blood using HPLC single wavelength ultraviolet detection (210 nm). Evaluation of standard method validation parameters was found to be satisfactory. The circulation of DPMP on the market is another example of psychoactive substances described decades ago in the patent literature which are beginning to be rediscovered by recreational drug communities. The ability to unambiguously identify and detect this psychoactive compound should therefore be of interest to those who are exposed to the recreational drugs field. PMID- 22055833 TI - Engaging people with diabetes in the post-summit world. PMID- 22055834 TI - Using a combined motivational and volitional intervention to promote exercise and healthy dietary behaviour among undergraduates. AB - AIMS: This study tested the impact of combining a motivational intervention based on protection motivation theory (PMT, Rogers, 1983 [18]) plus a volitional intervention based on action planning and coping planning, as a way to promote the prevention of type 2 diabetes among UK undergraduates. METHODS: Eighty-four participants were randomly assigned to either a control group or one of three experimental conditions: motivational intervention (PMT), volitional intervention (APCP), or combined motivational and volitional intervention (PMT&APCP). PMT variables, dietary and exercise behaviours were measured at three time-points over a four-week period. RESULTS: The motivational intervention significantly changed PMT variables. The combined motivational and volitional intervention significantly decreased fat intake and increased the frequency of exercise relative to all other groups, and significantly increased the amount of fruit and vegetables consumed relative to control and volitional intervention groups. CONCLUSIONS: These results suggest that motivational intervention is effective at changing cognitions but changing behaviour requires an intervention based on both motivation and volition. PMID- 22055835 TI - The safety, efficacy and predictors for HbA1c reduction of sitagliptin in the treatment of Japanese type 2 diabetes. AB - We evaluated the efficacy and safety of sitagliptin after 3 months' treatment in Japanese type 2 diabetic patients and examined changes in clinical factors. Baseline HbA1c, PPG, BMI, and duration of diabetes may be predictors of HbA1c reduction when using sitagliptin in Japanese type 2 diabetic patients. PMID- 22055836 TI - Morphology, ultrastructure and life cycle of Vitrella brassicaformis n. sp., n. gen., a novel chromerid from the Great Barrier Reef. AB - Chromerida are photoautotrophic alveolates so far only isolated from corals in Australia. It has been shown that these secondary plastid-containing algae are closely related to apicomplexan parasites and share various morphological and molecular characters with both Apicomplexa and Dinophyta. So far, the only known representative of the phylum was Chromera velia. Here we provide a formal description of another chromerid, Vitrella brassicaformis gen. et sp. nov., complemented with a detailed study on its ultrastructure, allowing insight into its life cycle. The novel alga differs significantly from the related chromerid C. velia in life cycle, morphology as well as the plastid genome. Analysis of photosynthetic pigments on the other hand demonstrate that both chromerids lack chlorophyll c, the hallmark of phototrophic chromalveolates. Based on the relatively high divergence between C. velia and V. brassicaformis, we propose their classification into distinct families Chromeraceae and Vitrellaceae. Moreover, we predict a hidden and unexplored diversity of the chromerid algae. PMID- 22055837 TI - Exploring semantic and phonological picture-word priming in adults who stutter using event-related potentials. AB - OBJECTIVE: Our aim was to investigate how semantic and phonological information is processed in adults who stutter (AWS) preparing to name pictures, following-up a report that event-related potentials (ERPs) in AWS evidenced atypical semantic picture-word priming (Maxfield et al., 2010). METHODS: Fourteen AWS and 14 typically-fluent adults (TFA) participated. Pictures, named at a delay, were followed by probe words. Design elements not used in Maxfield et al. (2010) let us evaluate both phonological and semantic picture-word priming. RESULTS: TFA evidenced typical priming effects in probe-elicited ERPs. AWS evidenced diminished semantic priming, and reverse phonological N400 priming. CONCLUSIONS: Results point to atypical processing of semantic and phonological information in AWS. Discussion considers whether AWS ERP effects reflect unstable activation of target label semantic and phonological representations, strategic inhibition of target label phonological neighbors, and/or phonological label-probe competition. SIGNIFICANCE: Results raise questions about how mechanisms that regulate activation spreading operate in AWS. PMID- 22055838 TI - Functional anatomy of subcortical circuits issuing from or integrating at the human brainstem. AB - The functional organization of the main human brainstem centers and circuits are described as revealed in post-mortem material with high-resolution structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) acquired at ultra-high magnetic field 7 T. The description is complemented with a conventional in vivo fiber tracking study of the descending motor pathways. This type of neuroanatomic depiction of nuclei and nerve tracts at very high spatial resolution opens new possibilities to analyze the fine structure and circuits of the human brainstem, at least in post-mortem material. PMID- 22055839 TI - Adiposity measures predict olfactory processing speed in older adult carriers of the apolipoprotein E epsilon4 allele. AB - OBJECTIVE: The current study investigated the relationship between adiposity and P3 latency. METHODS: Fifty-one adults in two age groups (18-25 and 65+) participated. Odor stimuli were delivered via olfactometer as participants focused on a computer screen. Each stimulus was followed by presentation on the screen of four odor identification choices. Participants attempted identification by button press. Olfactory event-related potentials (OERPs) were recorded. BMI and waist circumference were measured as indicators of adiposity. RESULTS: In bivariate analyses with all participants included, positive correlations for P3 latency with both BMI and waist circumference were observed, indicating that as adiposity increased latencies also increased. When each age group was separately examined, correlations between adiposity measures and latency remained statistically significant for older adults. Furthermore, ApoE epsilon4 allele status was examined. Latencies remained positively correlated with adiposity in older adult epsilon4 carriers; but not in non-carriers. CONCLUSIONS: This study indicates that adiposity predicts olfactory processing speed in older adults, specifically in epsilon4 carriers. SIGNIFICANCE: The results suggest that olfactory processing speed may be a useful measure for detecting and following the effects of adiposity on brain integrity and cognitive function in those at genetic risk for AD. PMID- 22055840 TI - A-waves in Guillain-Barre syndrome: correlation with electrophysiological subtypes and antiganglioside antibodies. AB - OBJECTIVE: To investigate the relationship of A-waves with conventional electrophysiological subtypes of Guillain-Barre syndrome (GBS), as well as with anti-ganglioside antibodies. METHODS: The subjects consisted of 30GBS patients who were classified into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, and unclassified based on the results of nerve conduction studies. "Abundant A-waves" were defined for the upper-limb nerves (median and ulnar nerves) using receiver-operator characteristic curves. The presence or absence of IgG anti-ganglioside antibodies was also noted. RESULTS: Abundant A-waves at weeks 3-6 from onset were observed in 64% of the 14 AIDP patients and 0% of 16 non-AIDP patients, and in 60% of 15 antibody-negative patients and 0% of 15 antibody-positive patients. In the earlier period, this relationship was less clear. The correlation between the conventional electrophysiological subtypes and antibodies was present, but was much weaker. CONCLUSIONS: Abundant A-waves in GBS after the acute phase were strongly associated with demyelination that was not mediated by antiganglioside antibodies, possibly through the mechanism of proximal re-excitation induced by electrical inhomogeneities due to segmental demyelination. SIGNIFICANCE: Abundant A-waves are promising as a novel reliable marker of demyelination. PMID- 22055841 TI - Cerebral effects of binge drinking: respective influences of global alcohol intake and consumption pattern. AB - OBJECTIVE: Binge drinking is a major health concern, but its cerebral correlates are still largely unexplored. We aimed at exploring (1) the cognitive step at which these deficits appear and (2) the respective influence of global alcohol intake and specific binge-drinking consumption pattern on this deficit. METHODS: On the basis of a screening phase (593 students), 80 participants were selected and distributed in four groups (control non-drinkers, daily drinkers, low and high binge drinkers). Event-related potentials (ERPs) were recorded while performing a simple visual oddball task. RESULTS: Binge drinking was associated with massive ERP impairments, starting at the perceptive level (P100/N100 and N170/P2) and spreading through the attentional (N2b/P3a) and decisional (P3b) ones. Moreover, these deficits were linked with global alcohol intake and also with the specific binge-drinking consumption pattern. CONCLUSIONS: Binge drinkers presented early and global ERP deficits, affecting basic and high-level cognitive stages. Moreover, we showed that binge drinking is deleterious for the brain because of alcohol consumption per se, and also because of its specific consumption pattern. SIGNIFICANCE: The present results show that binge-drinking habits lead to striking brain consequences, particularly because of the repeated alternation between intense intoxications and withdrawal episodes. PMID- 22055842 TI - The oscillating central network of Essential tremor. AB - Essential tremor (ET) is a centrally driven tremor. It is meanwhile well established that it does not emerge from one single oscillator but an oscillatory network comprising most parts of the physiological central motor network. Several lines of evidence hint at the olivocerebellar system and the thalamus as key structures within this network whereas the cortical motor regions are only intermittently entrained in the tremor rhythm in thalamocortical loops. Dynamic changes in network composition and the interaction in symmetric loops seem to be specific to the generation of tremor. The same network in voluntary motor control is more fixed and subcortico-cortical interactions are preferentially via thalamocortical relays. Thus it is not primarily the network topography but the dynamics and interaction within the network that determines whether involuntary tremor or voluntary movements emerge. And this may be the basis for the selective effect of deep brain stimulation on tremor. PMID- 22055843 TI - The re-emergence of evoked potentials in multiple sclerosis; from diagnosis to prognostication. PMID- 22055844 TI - Comparison of calibration results for an extrapolation chamber obtained with different 90Sr+90Y secondary standard sources. AB - Two secondary standard systems of beta radiation were used to calibrate a PTW extrapolation chamber Model 23391. Three (90)Sr+(90)Y sources of different activities were used in this calibration procedure. Medium-term stability of the response of the chamber was also studied. The calibration was performed with and without field-flattening filters. The relative standard deviation of the obtained calibration factors was 8.3% for the aluminum collecting electrode and 4.1% for the graphite collecting electrode. PMID- 22055845 TI - Automated preparation of the dopamine D2/3 receptor agonist ligand [11C]-(+)-PHNO for human PET imaging studies. AB - Carbon-11 labelled (+)-4-Propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2 b][1,4]oxazin-9-ol ([(11)C]-(+)-PHNO) is used as a high-affinity state, dopamine D(2/3) receptor ligand in clinical PET studies. To facilitate its use, robust, rapid, efficient and GMP compliant methods are required for the manufacturing and QC testing processes. Additionally, to allow for full quantification of the resulting signal in the CNS, a reliable method is required to establish the parent plasma concentration over the course of the scan. This paper provides high quality methods to support clinical application of [(11)C]-(+)-PHNO. PMID- 22055846 TI - Phase II trial of adjuvant pelvic radiation "sandwiched" between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma. AB - OBJECTIVE: Uterine carcinosarcoma (CS) is a rare uterine tumor with an extremely poor prognosis. In the adjuvant setting, efficacy has been shown with radiotherapy (RT), systemic chemotherapy, or both. This is the first report describing the efficacy and toxicity of adjuvant ifosfamide or ifosfamide plus cisplatin "sandwiched" with RT in patients with surgically staged and completely resected uterine carcinosarcoma. METHODS: Women with surgically staged CS with no gross residual disease were initially administered ifosfamide (1.2 g/m(2)/day*5 days) with cisplatin (20 mg/m(2)/day*5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin (20 mg/m(2)/day*5 days) every 3 weeks. Similar to the GOG trial in recurrent CS (Sutton et al., 2000), the addition of cisplatin added toxicity without additional efficacy, so mid-study, the cisplatin was eliminated from the regimen. Toxicities were recorded and disease-free survival (DFS) was calculated with Kaplan-Meier statistical methods. RESULTS: In total, 12 patients received ifosfamide and cisplatin and 15 patients received ifosfamide alone, both 'sandwiched' with RT. The median follow up was 35.9 months (range 6-88). The 2 year DFS was similar in both the ifosfamide/cisplatin and ifosfamide groups (log-rank p=0.16), so they were combined for analysis. 19 patients (70%) completed the protocol. As expected, stage 1 patients had a better 2-year DFS (18.75 +/- 1.12 months; log-rank p=0.008 when compared to stages 2, 3, 4). Also, in stages 2, 3 and 4 patients, the DFS was 15.81 +/- 1.73 months. Grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 18%, 4% and 4% of cycles, respectively. CONCLUSIONS: Ifosfamide "sandwiched" with RT appears to be an efficacious regimen for surgically staged CS patients with no residual disease, even in patients with advanced stage. The addition of cisplatin to the regimen added toxicity without improving efficacy. Even with ifosfamide alone, the efficacy of this 'sandwich' regimen comes with a moderate but tolerable toxicity profile. PMID- 22055847 TI - Assessment of peripheral tissue perfusion disorder in streptozotocin-induced diabetic rats using dynamic contrast-enhanced MRI. AB - PURPOSE: To assess peripheral tissue perfusion disorder in streptozotocin (STZ) induced diabetic rats by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: A rat diabetes model was produced by intravenous injection of STZ. Diabetic rats were sustainably treated with either saline or insulin using an Alzet osmotic pump. Hind paw tissue perfusion was measured by signal intensity (SI) enhancement after gadolinium diethylenetriaminepentaacetic acid injection in DCE-MRI study and quantified using the initial area under the SI-time curve (IAUC). Peripheral tissue uptake of [(14)C]iodoantipyrine (IAP) was also determined as a marker of tissue blood flow for comparison with the IAUC value indicating tissue perfusion. RESULTS: STZ caused hyperglycemia at 1 and 2 weeks after injection. Treatment with insulin significantly alleviated hyperglycemia. At 2 weeks after STZ injection, peripheral tissue perfusion was clearly reduced in the diabetic rats and its reduction was significantly improved in the insulin-treated diabetic rats. Tissue perfusion evaluated by DCE-MRI was similar to the tissue blood flow measured by [(14)C]IAP uptake. CONCLUSION: Our findings demonstrated that DCE-MRI can assess peripheral tissue perfusion disorder in diabetes. DCE-MRI could be suitable for noninvasive evaluation of peripheral tissue perfusion in both preclinical and clinical studies. It may also be useful for developing novel drugs to protect against diabetic vascular complications. PMID- 22055848 TI - Assessment of stiffness changes in the ex vivo porcine aortic wall using magnetic resonance elastography. AB - Magnetic resonance elastography (MRE) is a noninvasive phase-contrast technique for estimating the mechanical properties of tissues by imaging propagating mechanical waves within the tissue. In this study, we hypothesize that changes in arterial wall stiffness, experimentally induced by formalin fixation, can be measured using MRE in ex vivo porcine aortas. In agreement with our hypothesis, the significant stiffness increase after sample fixation was clearly demonstrated by MRE and confirmed by mechanical testing. The results indicate that MRE can be used to examine the stiffness changes of the aorta. This study has provided evidence of the effectiveness of using MRE to directly assess the stiffness change in aortic wall. The results offer motivation to pursue MRE as a noninvasive method for the evaluation of arterial wall mechanical properties. PMID- 22055849 TI - Evaluation of MRI issues at 3-Tesla for a hospital identification (ID) wristband. AB - BACKGROUND AND PURPOSE: A recent report suggested that a serious burn injury was due to the presence of the identification (ID) wristband. As such, in lieu of removing or padding hospital ID wristbands in all patients prior to magnetic resonance imaging (MRI), testing may be performed to characterize risks for ID wristbands. Therefore, the purpose of this investigation was to evaluate the magnetic field interactions, heating and artifacts at 3 T for a hospital ID wristband. MATERIALS AND METHODS: Standardized test methods were used to evaluate magnetic field interactions, MRI-related heating, and artifacts at 3 T for a hospital ID wristband. RESULTS: There were no magnetic field interactions. MRI related heating evaluated at a relatively high, MR system-reported, whole body averaged specific absorption rate (2.9 W/kg) did not increase above the background level. The artifacts related to the ink used for printing were "small" for one toner and "large" for the other in relation to the dimensions of the printing. CONCLUSIONS: Based on the tests performed, this particular hospital ID wristband is considered MR safe and will not pose a hazard to a patient undergoing an MRI examination. Importantly, it is not necessary to remove this item for a patient referred for MRI. PMID- 22055850 TI - Correlation of MRI findings to histology of acetaminophen toxicity in the mouse. AB - Acetaminophen (APAP) toxicity is responsible for approximately half of all cases of acute liver failure in the United States. The mouse model of APAP toxicity is widely used to examine mechanisms of APAP toxicity. Noninvasive approaches would allow for serial measurements in a single animal to study the effects of experimental interventions on the development and resolution of hepatocellular necrosis. The following study examined the time course of hepatic necrosis using small animal magnetic resonance imaging (MRI) following the administration of 200 mg/kg ip APAP given to B6C3F1 male mice. Mice treated with saline served as controls (CON). Other mice received treatment with the clinical antidote N acetylcysteine (APAP+NAC). Mouse liver pathology was characterized using T1- and T2-weighted sequences at 2, 4, 8 and 24 h following APAP administration. Standard assays for APAP toxicity [serum alanine aminotransaminase (ALT) levels and hematoxylin and eosin (H&E) staining of liver sections] were examined relative to MRI findings. Overall, T2 sequences had a greater sensitivity for necrosis and hemorrhage than T1 (FLASH) images. Liver injury severity scoring of MR images demonstrated increased scores in the APAP mice at 4, 8 and 24 h compared to the CON mice. APAP+NAC mice had MRI scores similar to the CON mice. Semiquantitative analysis of hepatic hemorrhage strongly correlated with serum ALT. Small animal MRI can be used to monitor the evolution of APAP toxicity over time and to evaluate the response to therapy. PMID- 22055851 TI - A dual-tuned quadrature volume coil with mixed lambda/2 and lambda/4 microstrip resonators for multinuclear MRSI at 7 T. AB - In this work, an eight-element by eight-element dual-tuned quadrature volume coil with a mix of capacitor terminated half-wavelength (lambda/2) and quarter wavelength (lambda/4) microstrip resonators is proposed for multinuclear magnetic resonance imaging/spectroscopy studies at 7 T. In the proton channel, lambda/2 microstrip resonators with capacitive terminations on both ends are employed for operation at higher frequency of 298.1 MHz; in the heteronucleus channel, capacitor-terminated lambda/4 resonators, suitable for low frequency operations, are used to meet the low frequency requirement. This mixed structure design is particularly advantageous for high field heteronuclei magnetic resonance applications with large difference in Larmor frequency of the nuclei in question. The proposed design method makes it much easier to perform frequency tuning for heteronucleus channel using a variable capacitor with a practical capacitance range. As an example, a dual-tuned volume coil for (1)H/(13)C mouse spectroscopic imaging was proposed to demonstrate the feasibility of this method. The finite difference time-domain method is first used to model this dual-tuned volume coil and calculate the B(1) field distributions at two frequencies. Transmission parameters (S(21)) measured between the proton channel and the carbon channel are -50 dB at 75 MHz and -35 dB at 298 MHz, showing the excellent isolation between the two channels at 7 T. The proton image and (13)C FIDCSI image of a corn oil phantom on the axial plane at 7 T demonstrate the feasibility of the proposed method. A preliminary proton image of a mouse on the sagittal plane is also acquired using the proposed dual-tuned volume coil at 7 T, illustrating a fairly uniform B(1) field and sufficient image coverage for imaging in mice. PMID- 22055852 TI - A 3D balanced-SSFP Dixon technique with group-encoded k-space segmentation for breath-held non-contrast-enhanced MR angiography. AB - A three-dimensional balanced steady-state free precession (b-SSFP)-Dixon technique with a novel group-encoded k-space segmentation scheme called GUINNESS (Group-encoded Ungated Inversion Nulling for Non-contrast Enhancement in the Steady State) was developed. GUINNESS was evaluated for breath-held non-contrast enhanced MR angiography of the renal arteries on 18 subjects (6 healthy volunteers, 12 patients) at 3.0 T. The method provided high signal-to-noise and contrast renal angiograms with homogeneous fat and background suppression in short breath-holds on the order of 20 s with high spatial resolution and coverage. GUINNESS has potential as a short breath-hold alternative to conventional respiratory-gated methods, which are often suboptimal in pediatric subjects and patients with significant diaphragmatic drift/sleep apnea. PMID- 22055853 TI - MR susceptibility artifact due to occupational cause: an unusual case. PMID- 22055854 TI - Age-related diffusion patterns in human lumbar intervertebral discs: a pilot study in asymptomatic subjects. AB - Diffusion tensor imaging (DTI) may provide an accurate noninvasive method of detecting degenerative matrix alterations in human lumbar intervertebral discs (IVDs). This study aimed to investigate age-related degenerative changes in human lumbar IVDs using DTI. Thirty asymptomatic volunteers ranging in age from 25 to 67 years underwent single-shot diffusion weighted echo-planar imaging on a 3 T scanner. DTI-derived metrics including fractional anisotropy (FA) and mean diffusivity (MD) were analyzed by a histogram analysis method. A Mann-Whitney test was used to compare subject groups (young and elderly) with respect to the diffusion measures, and piecewise linear regression was used to characterize the change in each metric as a function of age. We found significant age-related changes in the elderly adult group, with decrease of MD (11%, P<.001) and increase of FA (20%, P<.001). Our results demonstrate that the degenerative related changes taking place in the IVDs through aging can be quantitatively accessed by DTI-derived metrics, while the morphologic changes are difficult to be identified in conventional T(2)-weighted images. Our initial findings suggest that it would be worthwhile to validate the relationship between DTI metrics and the actual degenerative status of IVDs using extracted disc samples and to extend it to studies on patients with degenerative discs in order to further explore the clinical usefulness and relevance of DTI. PMID- 22055855 TI - Functional magnetic resonance imaging of awake monkeys: some approaches for improving imaging quality. AB - Functional magnetic resonance imaging (fMRI) at high magnetic field strength can suffer from serious degradation of image quality because of motion and physiological noise, as well as spatial distortions and signal losses due to susceptibility effects. Overcoming such limitations is essential for sensitive detection and reliable interpretation of fMRI data. These issues are particularly problematic in studies of awake animals. As part of our initial efforts to study functional brain activations in awake, behaving monkeys using fMRI at 4.7 T, we have developed acquisition and analysis procedures to improve image quality with encouraging results. We evaluated the influence of two main variables on image quality. First, we show how important the level of behavioral training is for obtaining good data stability and high temporal signal-to-noise ratios. In initial sessions, our typical scan session lasted 1.5 h, partitioned into short (<10 min) runs. During reward periods and breaks between runs, the monkey exhibited movements resulting in considerable image misregistrations. After a few months of extensive behavioral training, we were able to increase the length of individual runs and the total length of each session. The monkey learned to wait until the end of a block for fluid reward, resulting in longer periods of continuous acquisition. Each additional 60 training sessions extended the duration of each session by 60 min, culminating, after about 140 training sessions, in sessions that last about 4 h. As a result, the average translational movement decreased from over 500 MUm to less than 80 MUm, a displacement close to that observed in anesthetized monkeys scanned in a 7-T horizontal scanner. Another major source of distortion at high fields arises from susceptibility variations. To reduce such artifacts, we used segmented gradient-echo echo-planar imaging (EPI) sequences. Increasing the number of segments significantly decreased susceptibility artifacts and image distortion. Comparisons of images from functional runs using four segments with those using a single-shot EPI sequence revealed a roughly twofold improvement in functional signal-to-noise ratio and 50% decrease in distortion. These methods enabled reliable detection of neural activation and permitted blood-oxygenation-level-dependent-based mapping of early visual areas in monkeys using a volume coil. In summary, both extensive behavioral training of monkeys and application of segmented gradient-echo EPI sequence improved signal-to-noise ratio and image quality. Understanding the effects these factors have is important for the application of high field imaging methods to the detection of submillimeter functional structures in the awake monkey brain. PMID- 22055856 TI - Robustness of fat quantification using chemical shift imaging. AB - The purpose of this study was to investigate the effect of parameter changes that can potentially lead to unreliable measurements in fat quantification. Chemical shift imaging was performed using spoiled gradient echo sequences with systematic variations in the following: two-dimensional/three-dimensional sequence, number of echoes, delta echo time, fractional echo factor, slice thickness, repetition time, flip angle, bandwidth, matrix size, flow compensation and field strength. Results indicated no significant (or significant but small) changes in fat fraction with parameter. The significant changes can be attributed to the known effects of T1 bias and two forms of noise bias. PMID- 22055857 TI - Preface. Spatially resolved nuclear magnetic resonance (NMR). PMID- 22055858 TI - A practical multinuclear transceiver volume coil for in vivo MRI/MRS at 7 T. AB - A practical multinuclear transceiver RF volume coil with improved efficiency for in vivo small animal (1)H/(13)C/(23)Na MR applications at the ultrahigh magnetic field of 7 T is reported. In the proposed design, the coil's resonance frequencies for (1)H and (13)C are realized by using a traditional double-tuned approach, while the resonant frequency for (23)Na, which is only some 4 MHz away from the (13)C frequency, is tuned based upon (13)C channel by easy-operating capacitive "frequency switches". In contrast to the traditional triple-tuned volume coil, the volume coil with the proposed design possesses less number of resonances, which helps improve the coil efficiency and alleviate the design and operation difficulties. This coil design strategy is advantageous and well suitable for multinuclear MR imaging and spectroscopy studies, particularly in the case where Larmor frequencies of nuclei in question are not separate enough. The prototype multinuclear coil was demonstrated in the desired unshielded design for easy construction and experiment implementation at 7 T. The design method may provide a practical and robust solution to designing multinuclear RF volume coils for in vivo MR imaging and spectroscopy at ultrahigh fields. Finite difference time domain method simulations for evaluating the design and 7-T MR experiment results acquired using the prototype coil are presented. PMID- 22055859 TI - Effects of manganese injected into rat nostrils: implications for in vivo functional study of olfaction using MEMRI. AB - Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful tool for visualizing neuronal pathways and mapping brain activity modulation. A potential drawback of MEMRI lies in the toxic effects of manganese (Mn), which also depend on its administration route. The aim of this study was to analyze the effects of Mn doses injected into the nostrils of rats on both olfactory perception and MRI contrast enhancement. For this purpose, doses in the range 0-8 MUmol MnCl(2) were tested. Behavioral items were quantified with and without odor stimulation during the first 2 h following Mn injection. The MRI study was performed after 16 h of intermittent olfactory stimulations. Behavioral results showed that, during the early period following Mn administration, spontaneous motor activity was not affected, while odor-related behaviors were dose-dependently reduced. MRI results showed that, in the primary olfactory cortex, contrast was rapidly enhanced for Mn doses up to 0.3 MUmol and very slowly above. This dose of 0.3 MUmol Mn can thus be taken as the optimal dose for injection into rat nostrils to ensure a reproducible contrast in MRI studies while sparing olfactory perception. PMID- 22055860 TI - Comparative action of cathepsins D, B, H, L and of a new lysosomal cysteine proteinase on rabbit myofibrils. AB - Specific action of cathespins D, B, H, L, and of a new high Mr (molecular weight relative to hydrogen) cysteine proteinase, on rabbit muscle myofibrils was studied at pH 5.7 by following changes affecting their ATPase activities, their calcium sensitivity, their effect on the ultrastructure, as well as the electrophoretic pattern of the contractile proteins in the presence of SDS. With regard to the Mg?Ca-enhanced ATPase activity, all these proteinases had a very similar effect. A decrease in this activity was thus noted concomitantly with a shift of the straight-line graph obtained when plotting the present acto-myosin ATPase activity versus KCl concentrations. Cathepsins D, B, L and the high Mr cysteine proteinase induced a decrease in both the calcium ATPase activity of myosin and the calcium sensitivity of myofibrils. On the contrary, the Mg-EGTA dependent ATpase activity was increased. Except for cathepsin H, extensive hydrolysis of proteins occurred in myofibrils treated with each of the lysosomal proteinases tested. However, different specificities could be distinguished. On the one hand, cathepsins D and B affected mainly myofibrillar protein running above and below actin, respectively, on SDS-polyacrylamide gel electrophoresis; on the other hand, the high Mr cysteine proteinase exhibited broader specificity since most of the proteins were hydrolyzed irrespective of their Mr. Myofibrils incubated with cathepsins B and the high Mr cysteine proteinase showed ultrastructural modifications at the level of Z-line, M-bands and A-bands. Myofibrils treated with cathepsin D and cathepsin H appeared almost unaltered. On the basis of these characteristics, cathepsin H hardly affected myofibrils. These results provide evidence for the involvement of the lysosomal proteinases in the meat ageing process and are discussed in regard to the changes occurring at the myofibrillar level during conversion of muscle into meat. PMID- 22055861 TI - Fat content and fatty acid pattern in muscle and adipose tissue from differently reared calves. AB - Two groups of Simmental calves were fed a milk replacer diet or were early weaned and slaughtered at the age of 4 months. Two muscles and two adipose tissue samples were removed, the lipids were extracted by chloroform-methanol and the fatty acid composition was analyzed by gas chromatography after transesterification with Na-methylate. Total lipid contents in both muscles were relatively small (<2%) Due to high phospholipid content, veal muscle lipids contain a high proportion of polyene fatty acids which accounted for more than 30%. Adipose tissue consists predominantly of oleic acid (from 34% to 37%) and palmitic acid (from 27% to 29%). In extractable perinephric fat, milk replacer diet caused significantly higher myristic acid (C(14)) values and, accordingly, lower oleic (C(18:1)) values. PMID- 22055862 TI - Comparison of ultrasonic measurement of backfat depth on live pigs and carcases with a digital recording instrument. AB - A hand-held, digital recording ultrasonic backfat tester (Sonalyser) was used on 200 live pigs and their carcases to predict carcase P2 backfat depth measured with the Introscope optical probe. Readings were taken on live pigs at a position which approximated to the P2 site on the carcase. This site was tattooed. Sonalyser and Introscope readings were taken on the carcase at the P2 site and at the tattooed site. Regression equations of Introscope readings as a function of Sonalyser live pig and carcase measurements were developed. Calculation of partial F values showed the Sonalyser was more precise in measuring backfat on the live pig than the carcase. With R(2) = 0.77 and residual standard deviation (rsd) = 1.35 mm was judged to be acceptable for predicting carcase Introscope backfat from live pig measurement. Due to the lower precision, and other practical limitations to its use in abattoirs, the Sonalyser was not suitable for measuring backfat on the carcase. The limiting factors may have contributed to the lower R(2) (0.69) and higher rsd (1.55 mm) of the regression between Sonalyser and Introscope carcase fat depth. PMID- 22055863 TI - Comparative lipid composition of porcine muscles at different anatomical locations. AB - The influence of anatomical location on the intramuscular lipids was studied in Large White pigs. The amount of total, neutral and polar lipids and the composition of fatty acids of the above three fractions were determined for Longissimus dorsi (LD) at two points and Transversus abdominis (TA) and Biceps femoris (BF) taken from the two half carcasses of an animal. The symmetrical samples from the same animal had identical intramuscular lipid characteristics. The three muscles did not show significant differences in their total (2.8 to 2.4g/100g) and neutral (2.1 to 1.4g/100g) lipid contents. The amount of polar lipids was characteristic of every muscle (0.65 g, 0.84 g and 0.97 g per 100 g, respectively, in LD, BF and TA). The fatty acid composition of neutral lipids was influenced by the type of muscle. Polar lipid had similar fatty acid composition in the three muscles. The intramuscular lipids contained appreciable amounts of essential fatty acids of the family n-6; interestingly, a part of which (25% of EFA) was the long chain fatty acid (C20 and C22) located in the polar lipids. PMID- 22055864 TI - The use of video image analysis for quantitative measurement of visible fat and lean in meat: Part 3- lipid content variation in commercial processing beef and its prediction by image analysis. AB - Video image analysis (VIA) is now routinely used by a number of large meat processing companies to measure 'on-line' the fat and lean contents of boneless meat. Earlier limited work had indicated a good correlation between visible fat and chemical lipid. Establishing this relationship would allow manufacturers using VIA to accurately predict the lipid content in boneless meat. Accordingly, data have been collected (from 168 carcasses sampled over a 7-month period) on the lipid, moisture and lipid-free dry matter contents of three subcutaneous (SCF) and two intermuscular (IMF) fat depots from selected cuts of processing beef forequarter. The intramuscular fat contents of five lean sites were also measured. With very minor exceptions, there were no significant differences in lipid, moisture or dry matter contents within sites or between sites of the same depot type. However, highly significant differences (P > 0.01) between depot types were detected during the sampling period. There was poor correlation of lipid content between different depot sites. Equations derived from the data were applied to a commercial operation and compared to chemical analysis. In all cases, VIA predicted values showed very good agreement with analytical results (r = 0.94). Similar equations are now being developed for processing lamb and pork. PMID- 22055865 TI - The use of video image analysis for quantitative measurement of visible fat and lean in meat: Part 4- application of image analysis measurement techniques to minced meats. AB - The quantitative measurement of fat in minced meat by video techniques has, to date, been impractical due to the nature of the raw material and camera limitations in particle resolution. The latter have been enhanced by improving the optical system and by illuminating the meat with a limited wavelength ultraviolet light source. Problems with fat smear and drip stain, causing over- and under-estimation of fat, respectively, have been overcome by better control of mincing conditions. Tempering of the meat to between -2 degrees C and -5 degrees C before mincing gave the best results. The level of fat detection was unchanged for up to 20 min after mincing, but, by 2 h, the initial value had fallen by 50%. Magnifying the field of view, thus reducing the sample size measured by 50%, did not adversely affect results with 4mm-10mm diameter mince. The system could not accurately resolve mince below 4 mm. Estimation of total lipid from video data using prediction equations was in good agreement with chemical analysis (r=0.99 for 10mm mince, r=0.95 for 4 mm mince). Video image analysis (VIA) can now be effectively extended to areas of meat processing using particulate meats. PMID- 22055866 TI - Biochemical factors influencing metmyoglobin formation in beef muscles. AB - To explain the different rates of metmyoglobin accumulation in bovine muscles, biochemical factors such as oxygen consumption rate, cytochrome a(+a(3)) content, myoglobin autoxidation and enzymic ferrimyoglobin reduction were studied. The measurements involved five cows and five bulls. Only six cows were used for Metmyoglobin Reducing Activity (MRA) measurements. Three muscles with different colour stability (Tensor fasciae latae, Psoas major and Diaphragma medialis) were chosen. Meat colour stability, as well as the oxido-reduction potential of myoglobin, were highly related to muscle type. The animal effect was low or non significant. Muscles with the poorest colour stability, such as Psoas major and Diaphragma medialis had the highest oxidative activities (oxygen consumption rate) and the highest myoglobin autoxidation rates. Enzymic ferrimyoglobin reduction, estimated either by spectrophotometric measurements from muscle homogenates in aerobic conditions ('Metmyoglobin Reductase Activity') or by reflectance measurements in anaerobic conditions (MRA), does not explain the differences observed in muscle colour stability. PMID- 22055867 TI - Structure of beef Longissimus dorsi muscle frozen at various temperatures: Part 1 histological changes in muscle frozen at -10, -22, -33, -78, -115 and -196 degrees C. AB - To elucidate the relationship between the lowering of freezing temperature and the distribution of ice crystals in frozen muscle, samples of beef Longissimus dorsi muscle were frozen at -10, -22, -33, -78, -115 and -196 degrees C. Histological preparations of these samples indicated that ice crystals were formed in muscles frozen at -10 degrees C intercellularly, at -22 degrees C inter and intracellularly, at -33 degrees C intercellularly and at -78, -115 and -196 degrees C only intracellularly. In muscles frozen at -78 degrees C, ice crystals in fibres were large; in those frozen at -115 degrees C they were relatively smaller; and in those frozen at -196 degrees C they were evenly distributed throughout the muscles. The greatest damage was caused at -22 degrees C due to the simultaneous formation of the ice intra- and intercellularly. The results indicated that the pattern of distribution of ice crystals at the latter temperature deviates from that predicted from a linear progression of change with temperature of freezing. PMID- 22055868 TI - Structure of beef Longissimus dorsi muscle frozen at various temperatures: Part 2 ultrastructure of muscles frozen at -10, -22, -33, -78 and -115 degrees C. AB - The changes in electron micrographs of muscles frozen at -10, -22, -33, -78 and 115 degrees C were analyzed. The ultrastructure of muscle successively changed with decreasing freezing temperature whereas light microscopy indicated anomalous behaviour at -22 degrees C. It appeared that, in muscles frozen at -10 degrees C, there was no freezing of water intracellularly; in those frozen at -22 degrees C, water was frozen intracellularly (but only in the I-band region); whereas, in muscles frozen at -33 degrees C, water was frozen inside the fibres, both in the I- and the A-bands. In muscles frozen at -78 and -115 degrees C, water is frozen intracellularly. These findings can be explained on the basis that, in the I-band region, the major protein is actin, which has a relatively high proportion of non polar residues and holds water weakly, whereas the predominant protein in the A band is myosin, which contains many polar residues and has a high water-holding capacity. PMID- 22055869 TI - Effect of electrical stimulation, high temperature conditions and ageing on muscle myofibrillar proteins. AB - Electrical stimulation, when accompanied by high temperature incubation, was found to lower the extractability of myofibrillar proteins and increase their degradation, particularly that of the myosin component. Troponin T and myosin light chain 2 were similarly affected. Troponin T and troponins I and C were degraded earlier during ageing in electrically stimulated muscles incubated at high temperature than in conventionally chilled muscles. PMID- 22055870 TI - Lipid and haemoprotein oxidation in meat emulsions. AB - Emulsions of refined additive-free lard, egg albumin and water were designed to study the effect of haemoproteins, iron salts and sodium chloride on lipid oxidation. It was found that ferric haematin pigments (metmyoglobin, methaemoglobin and heat denatured myoglobin and haemoglobin) were all catalysts of lipid oxidation whereas the oxy and carboxy derivatives were not effective. Emulsions prepared using meat of high and low metmyoglobin contents supported these findings. At the levels present in meat products, both ferrous and ferric salts were only very weak catalysts of the lipid oxidation compared with the ferric haematin complexes. Sodium chloride (1.5%) also possessed little or no pro oxidant activity in these systems. Emulsions prepared from fresh meat and fats from various sources and of different histories indicated that although, in model systems, peroxidising lipids can catalyse the oxidation of myoglobin, in meat and meat-based emulsions the effect is of minimal importance. PMID- 22055871 TI - Digestibility of collagenous fermented sausage in man. AB - The digestibility of the protein of a fermented collagenous sausage was studied in three patients with ileostomies with small bowel resections. The patients were given four ordinary meals each day with a total protein content of about 64g, half of which was derived from collagen. Pigskins from 6-month old scalded pigs were used as the collagen source. A fermented sausage, based on meat, was used as a reference and the patients with ileostomies served as their own controls. Urine was collected from two patients. The true nitrogen digestibilities were found to be 71-79 % for the collagenous diets and 69-85 % for the reference diets. Hydroxyproline digestibilities (apparent and true) for the collagenous diet periods were similar: 70-82 %. This indicated that collagen was digested to the same extent as other proteins. Amino acid patterns of ileal excreta distinctly differed for each of the two periods, further confirming that all the protein was not absorbed. Elevated excretion of hydroxyproline in the urine after ingestion of the collagenous sausage was found, mainly as peptide bound hydroxyproline, but accounted for about only 2% of the ingested hydroxyproline. It was concluded that collagenous fermented sausage is as digestible as a reference sausage based on meat even without prior heat treatment. PMID- 22055875 TI - Editorial. PMID- 22055874 TI - Genetic and epigenetic variations in inducible nitric oxide synthase promoter, particulate pollution, and exhaled nitric oxide levels in children. AB - BACKGROUND: Inducible nitric oxide synthase (iNOS; encoded by nitric oxide synthase isoform 2 [NOS2]) is the major enzyme for nitric oxide synthesis in airways. As such, measurement of fractional concentration of exhaled nitric oxide (Feno) provides an in vivo assessment of iNOS activity. Short-term exposure to air pollution, haplotypes, and DNA methylation in the NOS2 promoter has been associated independently with iNOS expression, Feno levels, or both. OBJECTIVE: We aimed to examine the effects of ambient air pollutants, NOS2 promoter haplotypes, and NOS2 promoter methylation on Feno levels in children. METHODS: We selected 940 participants in the Children's Health Study who provided buccal samples and had undergone Feno measurement on the same day. DNA methylation was measured with a bisulfite-PCR Pyrosequencing assay. Seven single nucleotide polymorphisms captured the haplotype diversity in the NOS2 promoter. Average particulate matter with an aerodynamic diameter of 2.5 MUm or less (PM(2.5)) and 10 MUm (PM(10)) or less and ozone and nitrogen dioxide levels 7 days before Feno measurement were estimated based on air pollution data obtained at central monitoring sites. RESULTS: We found interrelated effects of PM(2.5), NOS2 promoter haplotypes, and iNOS methylation on Feno levels. Increased 7-day average PM(2.5) exposure was associated with lower iNOS methylation (P = .01). NOS2 promoter haplotypes were globally associated with NOS2 promoter methylation (P = 6.2 * 10(-8)). There was interaction among 1 common promoter haplotype, iNOS methylation level, and PM(2.5) exposure on Feno levels (P(interaction) = .00007). CONCLUSION: Promoter variants in NOS2 and short-term PM(2.5) exposure affect iNOS methylation. This is one of the first studies showing contributions of genetic and epigenetic variations in air pollution-mediated phenotype expression. PMID- 22055876 TI - Sixty years of age-thirty years of meat research. PMID- 22055877 TI - Weight loss prediction during meat chilling. AB - A lumped parameter model for computing weight losses during meat chilling is proposed. The model is independent of the shape of the piece of meat and allows the fraction of fat and bone to be taken into account. With this information a distinction between the heat transfer and the mass transfer areas can be established. Also provided is a correction factor which permits the existence of temperature gradients inside the meat to be taken into consideration. With the aid of the model the effect of the different operating variables on weight losses is analysed. The values predicted by the model show good agreement with experimental data obtained by other authors for the chilling of steers, cows and lambs under a wide range of operating conditions. PMID- 22055878 TI - The similarities between the activities of the calcium activated sarcoplasmic factor and the kinase activating factor from rabbit skeletal muscle. AB - The similarity, that has been suggested by other investigators, between the kinase activating factor (KAF) and the calcium activated sarcoplasmic factor (CASF) of rabbit skeletal muscle is extended through a comparison of enzyme activities. Proteolytic activity on casein, the ability to activate skeletal muscle glycogen phosphorylase b kinase, inhibition by bovine heart KAF inhibitor and effects on myofibrillar integrity were examined using these two skeletal muscle proteases and a typical bacterial protease isolated from Pseudomonas perolens (ATCC 10757). The study demonstrated that the skeletal muscle proteases have more in common with each other than either protease has with the bacterial protease. The ability to influence the integrity of the myofibril was demonstrated by phase-contrast microscopy and SDS polyacrylamide gel electrophoresis. The KAF and CASF demonstrated similar effects that again differed from the bacterial protease effects. PMID- 22055879 TI - Anoxic storage of fresh beef. 1: Nitrogen and carbon dioxide storage atmospheres. AB - Anoxic gas-packaging of fresh beef was developed using a catalytic oxygen scavenging system. Retail cuts of fresh beef do not discolour during storage periods of up to 3 weeks at 0 degrees C in this system. The colour shelf-life of different muscles, subsequent to anoxic gas-packaging, are related to their intrinsic colour stabilities. Colour shelf-life decreases with length of storage period in the anoxic gas atmosphere. No differences in subsequent colour shelf life are found between meat stored in anoxic gas atmospheres of nitrogen or of carbon dioxide for up to 3 weeks at 0 degrees C. PMID- 22055880 TI - Post-mortem changes in cytoskeletal proteins of muscle. AB - Progressive changes have been identified in the solubility of muscle-cell proteins during post-mortem muscle ageing, particularly the cytoskeletal proteins, desmin and connectin. Ox sternomandibularis muscle was sampled immediately post mortem and up to six days later. It was homogenised and separated into three salt-soluble fractions: phosphate soluble, concentrated KI soluble and guanidine-HCl soluble. Proteins in each fraction were analysed on sodium dodecylsulphate polyacrylamide gels. Changes reported previously by other authors were confirmed. In addition desmin, which was restricted to the guanidine fraction, disappeared, apparently due to proteolysis during storage. Connectin was also partly lost from the guanidine fraction, possibly through increased solubility in the KI fraction. In this respect an unidentified polypeptide of 110 000 D appeared during storage. Desmin extracted from ox muscle was partially purified and identified by amino acid analysis. It apparently occurs in vivo as a network of linked collars around the Z-discs and its loss during post-mortem storage probably accounts for the ease with which stored muscle disintegrates into individual myofibrils on homogenisation. The disintegration of the cytoskeletal network can account for the post-mortem changes in the physical properties of muscle for the increased tenderness after cooking of stored meat. However, factors other than those related to changes in cytoskeletal proteins are responsible for the toughness of cooked, cold-shortened muscle since cold shortening prior to storage did not affect the distribution of proteins among the three salt fractions, nor the patterns obtained in gel analyses. PMID- 22055881 TI - Acceptability and storage stability of pork products with increased levels of polyunsaturated fatty acids. AB - Several batches of back bacon, belly bacon, Dutch-style cervelat sausage, pork loin roll, shoulder with fat, Bologna, Guelders ring sausage, Saxon liver sausage and luncheon meat were produced with increasing PUFA-levels using raw materials containing up to 30% linoleic acid in their fats. Only the preparation of the high linoleic fermented Dutch-style cervelat sausages gave problems. Fatty acid composition did not change during preparation, nor during a two months' storage of back bacon at 15 degrees C. Sensory evaluations of the products by an expert panel revealed only a few differences, mostly related to consistency. Penetration measurements on luncheon meat showed an increase of softness as the PUFA-level was increased Products were stored for up to 61 days at 4 or 15 degrees C. During storage, peroxide numbers and p-anisidine values were determined and sensory evaluations performed by an expert-panel. The unheated, and some of the pasteurised, highly unsaturated products appeared to be very susceptible to lipid oxidation. PMID- 22055882 TI - Identification and ecology of salt-requiring vibrio associated with cured meats. AB - Of 454 isolates of salt-requiring Vibrio, 17 were identified as V. costicola (Group 1) and 35 as V. costicola sub-sp. liquefaciens (Group 2). Although similar in many respects, the remaining 402 strains were associated with the spoilage of cured meats and differ from V. costicola in being non-motile, unable to grow in the presence of 20% (w/v) NaCl, negative in Mollers arginine test, and sensitive to penicillin. V. costicola was only isolated from cured meats and curing brines, whereas the unidentified Vibrio was also found in low salt (non-curing) environments of the factory, the slaughter and butchery areas (pork, bone dust, blood) and in faeces from the lairage. PMID- 22055883 TI - Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions. AB - Foxp3-expressing regulatory T cells (Tregs) play a crucial role in maintaining immune tolerance and homeostasis. One of the key issues for understanding Treg immunobiology is to determine how they suppress excessive or aberrant immune responses. Although a number of molecules have been reported to contribute to Treg suppressive function, the importance and precise role of each molecule is not clear. In this review, we propose and discuss that two modes of suppression can be distinguished. In the physiological and steady state, activation of naive T cells can be suppressed by natural Tregs via deprivation of activation signals including CD28 signal and IL-2 from antigen-reactive T cells, keeping the latter in a naive state in lymphoid tissues. These deprivation mechanisms are transiently abrogated in inflammatory conditions, allowing T cells to respond to antigen. In contrast, in highly inflammatory environments, for example, in microbial infection, activated Tregs acquire the capacity to kill or inactivate effector T cells and antigen-presenting cells, for example, via granzyme/perforin formation and IL-10 secretion, thereby actively damping excessive immune responses. Understanding these processes will help effectively controlling physiological and pathological immune responses via Tregs. PMID- 22055884 TI - A review of the relationships of pH with physical aspects of pork quality. AB - The pH(1)-index, defined as the percent of carcasses with pH < 6.0 at 45 min post mortem (p-m), gives some indication of the likely incidence of pale, soft, exudative (PSE) pork at 24 h or more p-m. However, there is considerable variation between nations in the subjective definition of PSE. Thus, pH data show that subjectively-defined PSE pork from one country might be regarded as normal pork in another country, and vice versa. The paleness of pork is inversely proportional to pH. The data from conventional monochromatic reflectance photometers are almost linearly related to pH whereas the data from the Goefo meter and fibre-optic (FO) probes follow curvilinear relationships which may be logarithmic. In the visible spectrum, correlations of FO reflectance with pH and muscle structure are strongest towards 700 nm. The relationship of pH with exudate (bag-drip) is biphasic with fluid losses increasing from pH 7 to about 6.1, then staying constant at lower pHs. This biphasic pattern is also seen in some, but not all, methods in which exudate is measured by applied pressure or in which myofibrillar water-holding capacity is measured by centrifugation. Electrical impedance and its primary determinants (resistance and capacitance in parallel) are directly proportional to pH but follow curvilinear relationships. There is at least some theoretical understanding of the relationship of pH with exudate, but much remains to be learnt about the causal relationships of pH with paleness or softness. Many of the older published studies in the field are marred by a failure to separate genetic causes of low-pH (porcine stress syndrome) from environmental causes (preslaughter handling, slaughter and refrigeration). PMID- 22055885 TI - Comparisons of patties using mixtures of ground meat from beef, pork and chevaline. AB - Sensory panels were used to evaluate five different ground meat products. The control product was ground beef and this was compared with products consisting of 70% beef and 30% pork; 50% beef, 30% pork, and 20% chevaline; 40% beef, 30% pork, and 30% chevaline; and 30% beef, 30% pork, and 40% chevaline. Analysis of sensory panel data revealed no significant difference (P < 0.05) in juiciness, flavor intensity, or flavor desirability. Raw and cooked samples of each of the five products were analyzed for proximate composition and were found to be comparable in nutritive value. There were small but non-significant differences in amino acid composition. PMID- 22055886 TI - Physical and sensory attributes of hot-processed and conventionally chilled hams and bellies from electrically stimulated and non-stimulated pork carcasses. AB - Forty-eight fresh hams and bellies were obtained from 24 market weight hogs (x = 94.5 kg) of which twelve were electrically stimulated (ES) by pulsing current immediately after exsanguination. The left side of each non-stimulated (NS) carcas was fabricated after conditioning for 3h post mortem at 17 degrees C (NS hot-processed). The left sides of ES carcasses were fabricated 1 h pm. The right sides were fabricated following a 24 h cooler chill at 2 degrees C (conventionally chilled: CP). Hams from ESCP carcasses had higher (P < 0.05) smokehouse yields than hams from NS carcasses. Hams that were hot-processed had higher smokehouse yields than the NSCP hams. Time of fabrication (1, 3 or 24h post mortem) did not affect smokehouse yields. Conventionally chilled bellies obtained from ES carcasses showed higher (P < 0.05) residual nitrite levels than those front electrically stimulated hot-processed (ESHP) carcasses. No differences were found for residual nitrite levels in the non-electrically stimulated sides. Panelists were unable to detect any sensory differences from the bacon strips. Sensory scores of ham slices were more juicy for non-stimulated hot-processed carcasses (NSHP) than those from ESHP carcasses. Panelists found the ham slices from NSCP carcasses to be more tender (P < 0.05) than those from electrically stimulated cold-processed (ESCP) carcasses. Results from this study clearly indicated that hot-processing of pork can provide hams and bellies that are acceptable for the production of cured hams and bacon of comparable quality and yield to those currently being produced under conventional processing methods. PMID- 22055887 TI - The influence of processing and refrigeration on the bacterial numbers on beef and sheep offals. AB - An investigation was carried out in a commercial abattoir on the influence of processing and refrigeration on a variety of beef and sheep offals. The influences of the different processes and the operations, to the bacterial load before refrigeration of the product, were determined. In general all the operations in the plant had an effect on the final bacterial load. The effect of inadequate refrigeration was noteworthy in all cases and this factor alone made the most significant contribution to the products having a poor shelf-life. PMID- 22055888 TI - Radiopharmaceuticals: when and how to use them to treat metastatic bone pain. AB - Bone pain due to skeletal metastases constitutes the most common type of cancer related pain. The management of bone pain remains challenging and is not standardized. In patients with multifocal osteoblastic metastases, systemic radiopharmaceuticals should be the preferred adjunctive therapy for pain palliation. The lack of general knowledge about radiopharmaceuticals, their clinical utility and safety profiles, constitutes the major cause for their underutilization. Our goal is to review the indications, selection criteria, efficacy, and toxicities of two approved radiopharmaceuticals for bone pain palliation: strontium-89 and samarium-153. Finally, a brief review of the data on combination therapy with bisphosphonates or chemotherapy is included. PMID- 22055889 TI - Radiopharmaceuticals for painful bone metastases: perspective from radiation oncology. PMID- 22055890 TI - Coordination of care in breast cancer survivors: an overview. AB - The number of breast cancer survivors in the United States is increasing. With longer survival, there has been an increase in the complexity and duration of posttreatment care. Multidisciplinary care teams are needed to participate across the broad spectrum of issues that breast cancer survivors face. In this setting, the need for well-established patterns of communication between care providers is increasingly apparent. We have created a multidisciplinary approach to the management of breast cancer survivors to improve communication and education between providers and patients. This approach could be extended to the care and management of survivors of other types of cancer. PMID- 22055891 TI - Documenting the symptom experience of cancer patients. AB - BACKGROUND: Cancer patients experience symptoms associated with their disease, treatment, and comorbidities. Symptom experience is complicated, reflecting symptom prevalence, frequency, and severity. Symptom burden is associated with treatment tolerance as well as patients' quality of life (QOL). OBJECTIVES: The purpose of this study was to document the symptom experience and QOL of patients with commonly diagnosed cancers. The relationship between symptoms and QOL was also explored. METHODS: A convenience sample of patients with the five most common cancers at a comprehensive cancer center completed surveys assessing symptom experience (Memorial Symptom Assessment Survey) and QOL (Functional Assessment of Cancer Therapy). Patients completed surveys at baseline and at 3, 6, 9, and 12 months thereafter. This article describes the study's baseline findings. RESULTS: Surveys were completed by 558 cancer patients with breast, colorectal, gynecologic, lung, or prostate cancer. Patients reported an average of 9.1 symptoms, with symptom experience varying by cancer type. The mean overall QOL for the total sample was 85.1, with results differing by cancer type. Prostate cancer patients reported the lowest symptom burden and the highest QOL. LIMITATIONS: The sample was limited in terms of racial diversity. Because of the method of recruitment, baseline data were collected 6-8 months after diagnosis, meaning that participants were at various stages of treatment. CONCLUSIONS: The symptom experience of cancer patients varies widely depending on cancer type. Nevertheless, most patients report symptoms, regardless of whether or not they are currently receiving treatment. Patients' QOL is inversely related to their symptom burden. PMID- 22055892 TI - Efficacy and safety of fentanyl pectin nasal spray compared with immediate release morphine sulfate tablets in the treatment of breakthrough cancer pain: a multicenter, randomized, controlled, double-blind, double-dummy multiple crossover study. AB - BACKGROUND: Immediate-release morphine sulfate (IRMS) remains the standard treatment for breakthrough cancer pain (BTCP), but its onset of effect does not match the rapid onset and short duration of most BTCP episodes. OBJECTIVE: This study will evaluate the efficacy/tolerability of fentanyl pectin nasal spray (FPNS) compared with IRMS for BTCP. METHODS: Patients (n = 110) experiencing one to four BTCP episodes/day while taking >= 60 mg/day oral morphine (or equivalent) for background cancer pain entered a double-blind, double-dummy (DB/DD), multiple crossover study. Patients completing a titration phase (n = 84) continued to a DB/DD phase: 10 episodes of BTCP were randomly treated with FPNS and oral capsule placebo (five episodes) or IRMS and nasal spray placebo (5 episodes). The primary end point was pain intensity (P < .05 FPNS vs. IRMS) difference from baseline at 15 minutes (PID(15)). Secondary end points were onset of pain intensity (PI) decrease (>= 1-point) and time to clinically meaningful pain relief (CMPR, >= 2 point PI decrease). Safety and tolerability were evaluated by adverse events (AEs) and nasal assessments. By-patient and by-episode analyses were completed. RESULTS: Compared with IRMS, FPNS significantly improved mean PID(15) scores. 57.5% of FPNS-treated episodes significantly demonstrated onset of PI improvement by 5 minutes and 95.7% by 30 minutes. CMPR (>= 2-point PI decrease) was seen in 52.4% of episodes by 10 minutes. Only 4.7% of patients withdrew from titration (2.4% in DB/DD phase) because of AEs; no significant nasal effects were reported. CONCLUSION: FPNS was efficacious and well tolerated in the treatment of BTCP and provided faster onset of analgesia and attainment of CMPR than IRMS. PMID- 22055893 TI - Diet and risk of inflammatory bowel disease. AB - BACKGROUND: A better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses. AIM: To review current knowledge on dietary risk factors for inflammatory bowel disease. METHODS: The PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease. RESULTS: Established non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case-control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate). CONCLUSIONS: A diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects. PMID- 22055894 TI - Inhibition of TNF-induced IL-6 by the TWEAK-Fn14 interaction in rheumatoid arthritis fibroblast like synoviocytes. AB - OBJECTIVES: TNF-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily, has been shown to increase cytokine production by rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). In this study, we determined the effect of interaction between TWEAK and its receptor fibroblast growth factor inducible-14 (Fn14) on cytokine expression in RAFLS. METHODS: RAFLS were obtained from surgical synovial specimens and used at passage 5-10. Cytokine protein and mRNA expression were measured with ELISA and real time-PCR, respectively. Apoptotic cells were detected by TUNEL assay. RelB activation was detected by Western blot analysis. RESULTS: TWEAK inhibited IL-6 production from total synovial cells from RA. TWEAK weakly induced FLS IL-6 and IL-8, but in contrast TWEAK dose-dependently inhibited IL-6 and IL-8 production by TNFalpha-activated FLS. TWEAK did not induce apoptosis in FLS but inhibited proliferation of TNFalpha-activated FLS. TWEAK induced RelB activation and suppressed IL-6 mRNA expression in TNFalpha-activated FLS and both of these phenomenon were abolished by inhibition of new protein synthesis with cycloheximide. CONCLUSIONS: TWEAK has a previously unsuspected inhibitory effect on cytokine production by TNFalpha activated RAFLS. This observation suggests that the effects of TWEAK on cytokine expression varies with the pro-inflammatory context, and that in TNFalpha activated states such as RA TWEAK may have a net inhibitory effect. PMID- 22055895 TI - Narcolepsy and effectiveness of gamma-hydroxybutyrate (GHB): a systematic review and meta-analysis of randomized controlled trials. AB - OBJECTIVES: Gamma-hydroxybutyrate (GHB) is currently authorized by the European Medicines Agency (EMA) to treat narcolepsy with cataplexy in adults, and by the Food and Drug Administration (FDA) to treat cataplexy in patients with narcolepsy, with an expanded indication for the treatment of excessive daytime sleepiness. This study meta-analyses and reviews the effectiveness of GHB on the clinical features of narcolepsy and its neurophysiological correlates. METHODS: A systematic review of the literature using Medline, Embase, Web of Science, Cochrane reviews, clinical-trials.gov, Scopus, Scirus, and a subsequent meta analysis were performed. Considered outcomes were: cataplexy attacks, subjective daytime sleepiness, sleep attacks, clinical global impression change (CGI-c), quality of life (QoL), hypnagogic hallucinations, sleep paralysis, mean sleep latencies on the multiple sleep latency test (MSLT) and maintenance of wakefulness test (MWT), nocturnal polysomnographic data. RESULTS: Nine randomized controlled trials reporting data on the effectiveness of GHB on narcolepsy were identified, for a total of 1,154 patients (771 patients in the GHB-treated group and 383 in the placebo group). The meta-analysis showed that GHB reduced cataplexy attacks both on a daily (weighted mean difference (WMD) -1.10; 95% confidence interval (CI) -1.29/-0.90, p < 0.00001) and a weekly basis (WMD -7.04; 95% CI -12.45/-1.63, p = 0.01), subjective nocturnal awakenings (WMD -1.33; 95% CI -1.78/-0.88, p < 0.00001), daytime sleep attacks on a weekly basis (WMD -9.30; 95% CI -15.92/-2.68, p = 0.006), subjective daytime sleepiness (WMD -2.81; 95% CI -4.13/-1.49, p < 0.0001) and sleep stage shifts (WMD -9.69; 95% CI -17.14/-2.24, p = 0.01). GHB increased sleep stages 3 + 4 (WMD 4.11; 95% CI 0.07/8.16, p = 0.05) and improved the CGI-c score (odds ratio (OR) 3.45; 95% CI 2.47/4.80, p < 0.00001). No significant changes were observed in night sleep latency, total sleep time, rapid-eye movement (REM) sleep and sleep stages 1 and 2. CONCLUSIONS: This meta-analysis demonstrates the effectiveness of GHB in treating major, clinically relevant narcolepsy symptoms and sleep architecture abnormalities. PMID- 22055896 TI - Types of abuse. AB - The four most common types of abuse are physical, sexual, emotional, and economic. Abuse is often further categorized into child abuse, intimate partner violence, and elder abuse. This article describes the important role that nurses and health care providers play in detecting, assessing, and reporting abuse. Armed with increased knowledge about signs and symptoms of abuse, nurses can guide patients to the appropriate resources. PMID- 22055897 TI - Abuse across the lifespan: prevalence, risk, and protective factors. AB - The results of abuse may include repeated abuse, chronic pain, and physical and emotional illnesses. For some, the result is death, but others thrive. Males and females are abused at similar rates, but males are more likely to experience physical assault and females are more likely to experience sexual assault. Males and females experience psychological abuse at the same rates and there is evidence that the effects of psychological abuse are as detrimental to long-term functioning as the effects of physical abuse. This article discusses partner violence in adults and adolescents, child maltreatment, and peer abuse in children and adolescents. PMID- 22055898 TI - Child abuse. AB - Child abuse can have a long-lasting and devastating effect on the growth and development of infants, children, and adolescents. Studies of abused and neglected children indicate that they have a higher rate of delayed intellectual development, poor school performance, aggressive behaviors, and social and relationship deficits compared with nonmaltreated children. Early recognition and appropriate treatment is one of the most important factors in preventing further child abuse and maltreatment. Every practitioner should be educated on the signs and symptoms of child abuse. The referral to child protective services is a necessity for the future well-being of the child. PMID- 22055899 TI - "I know it shouldn't but it still hurts" bullying and adults: implications and interventions for practice. AB - Bullying problems among children and adolescents are well documented but there is scant literature that examines this phenomenon among adults. This article contends that nurses must begin to assess adult patients for this type of violence. Direct questions about being bullied at work or in cyberspace should be added to assessments. Questioning will help bullying victims recognize that what they are going through is not acceptable and not their fault. It will also help identify patients who may need interventions beyond the treatment of the physically traumatic effects of bullying. PMID- 22055900 TI - Blind, deaf, and dumb: why elder abuse goes unidentified. AB - Elder abuse is a growing public health concern that affects elders regardless of residence, socioeconomic status, or geographic locale. Elder abuse includes acts of physical, psychological, verbal, and financial abuses as well as abandonment and neglect. Elder abuse has the potential to occur in multiple settings, whether in the home, rehabilitation centers, long-term care facilities, nursing homes, and/or senior day care centers. Children, family members, friends, and formal caregivers are prospective perpetrators of elder abuse. Public policy changes are necessary to standardize and delineate guidelines and procedures for the detection and prevention of elder abuse in the future. PMID- 22055901 TI - The relationship between abuse and depression. AB - Very strong links exist between abuse and depression in clinical practice. Abuse and depression often coexist in the victims and perpetrators of abuse. In nursing practice, responding to patients, particularly women, presenting with depression or depressive symptoms requires an understanding of the underlying and perhaps hidden issues of abuse and violence. Women who have experienced trauma often are diagnosed with depression, when in fact they have symptoms more consistent with posttraumatic stress disorder. Furthermore, depression often improves over time, when women manage to escape the abuse and violence in the relationship. PMID- 22055902 TI - Family issues associated with military deployment, family violence, and military sexual trauma. AB - Today's military has a greater percentage of families and children in comparison with previous generations. There are many, and unique, demands on military families made by the ongoing conflicts, and military life can be stressful. The presence of an increasing number of stressors is associated with an increased likelihood of domestic violence in military families and sexual trauma in service members. In this article, literature and research are presented to provide an overview of military deployment and families, and the effect of deployment on families; this is followed by a review of research on family violence and military sexual trauma. PMID- 22055903 TI - Workplace violence in nursing today. AB - Workplace violence is not a new phenomenon and is often sensationalized by the media when an incident occurs. Verbal abuse is a form of workplace violence that leaves no scars. However, for nurses, the emotional damage to the individual can affect productivity, increase medication errors, incur absenteeism, and decrease morale and overall satisfaction within the nursing profession. This results in staffing turnover and creates a hostile work environment that affects the culture within the organization. PMID- 22055904 TI - The impact of interpersonal violence on health care. AB - Interpersonal violence is prevalent in our society. Unfortunately, given the current stressors on individuals, families, and communities, the incidences of child abuse, interpersonal violence, and elder abuse are increasing. The economic impact on health care costs is significant. There are many contributing factors to abuse and they are all public health issues that must be addressed for these abuses to cease. This article describes the indicators of interpersonal violence, and outlines strategies for assessment and prevention. PMID- 22055905 TI - Community services for victims of interpersonal violence. AB - Interpersonal violence can be categorized into youth violence, childhood maltreatment, intimate partner violence, elder abuse, or sexual violence. Just as there are several different victims of interpersonal violence, there are various different community services and prevention programs for each particular type of interpersonal violence. This article reviews the literature on community services and prevention available for all victims of interpersonal violence, and examines the literature on whether these programs are effective. PMID- 22055906 TI - Domestic and institutional elder abuse legislation. AB - Statutes pertinent to elder abuse vary widely. This article provides examples of organizational structure, dependency and age of the victim, definitions of abuse, classification of penalties, and investigation processes. Health care providers must learn their state's elder abuse laws and review any operating manuals produced from the statutes or regulations. All health care workers must know and implement the law to protect the welfare of older persons. PMID- 22055907 TI - Meeting the 2015 Millennium Development Goals with new interventions for abused women. AB - In a developing country such as Pakistan, where illiteracy, poverty, gender differences, and health issues are prevalent, violence against women is a commonly observed phenomenon. The rising incidences of abuse among women indicate a need to introduce evidence-based community-derived interventions for meeting Millennium Developmental Goals by 2015. This article discusses the application of counseling, economic skills building, and microcredit programs as practical and effective interventions to improve the health outcomes of abused women and, therefore, improving maternal and child health in the Pakistani society. PMID- 22055908 TI - Victims of abuse. Preface. PMID- 22055909 TI - Human chorionic gonadotrophin regression rate as a predictive factor of postmolar gestational trophoblastic neoplasm in high-risk hydatidiform mole: a case-control study. AB - OBJECTIVE: The aim of this study was early prediction of postmolar gestational trophoblastic neoplasm (GTN) after evacuation of high-risk mole, by comparison of human chorionic gonadotrophin (hCG) regression rates. STUDY DESIGN: Fifty patients with a high-risk mole initially and spontaneously regressing after molar evacuation were selected from January 1, 1996 to May 31, 2010 (spontaneous regression group). Fifty patients with a high-risk mole initially and progressing to postmolar GTN after molar evacuation were selected (postmolar GTN group). hCG regression rates represented as hCG/initial hCG were compared between the two groups. The sensitivity and specificity of these rates for prediction of postmolar GTN were assessed using receiver operating characteristic curves. Multivariate analyses of associations between risk factors and postmolar GTN progression were performed. RESULTS: The mean regression rate of hCG between the two groups was compared. hCG regression rates represented as hCG/initial hCG (%) were 0.36% in the spontaneous regression group and 1.45% in the postmolar GTN group in the second week (p=0.003). Prediction of postmolar GTN by hCG regression rate revealed a sensitivity of 48.0% and specificity of 89.5% with a cut-off value of 0.716% and area under the curve (AUC) of 0.759 in the 2nd week (p<0.001). In patients with an hCG regression rate over 0.716% in the 2nd week, the hazard ratio for progression to postmolar GTN was 3.00 by multivariate analysis (p<0.001). CONCLUSION: Differences in hCG regression rates between spontaneous regression and postmolar GTN groups became evident from the second week following molar evacuation. The occurrence of postmolar GTN could be predicted as early as the second week by comparing regression rates. hCG regression rate is easily obtainable and a predictive factor for postmolar GTN. PMID- 22055910 TI - Fat necrosis of the abdominal pannus following caesarean section in patients with morbid obesity. PMID- 22055911 TI - [Drug interactions in primary care and patient safety]. PMID- 22055912 TI - [The importance of including the opinion of adolescents in activities against the use of alcohol, tobacco and drugs]. PMID- 22055913 TI - [Tool for prioritizing the strategies for improving the safety of prescribing in family medicine]. PMID- 22055914 TI - [Echo from Dr. Capote and the impact factor]. PMID- 22055915 TI - [Clinical safety in primary care: medical errors (II)]. AB - The first article of this series on Clinical Safety was dedicated to the epidemiology and systemic preventive policies. In the present review we focus on medical errors with special emphasis on diagnostic type errors. These errors sometimes arise from the elusive characteristics of the disease itself, the way in which the patients present their symptoms, and the characteristics of the professionals themselves. If we consider a general practitioner as a diagnostic machine, --paradigm of "physician as a robot"-- it would be easier for us to accept some cognitive limitations and introduce institutional strategies that would humanise the treatment occasionally received. More specifically we will examine three strategies for improving clinical reasoning: recognising dangerous situations, metacognition, and an internal supervisor. PMID- 22055916 TI - [Validation of the abbreviated Zarit scales for measuring burden syndrome in the primary caregiver of an elderly patient]. AB - OBJECTIVE: To determine which abbreviated Zarit Scale (ZS) better evaluates the burden of the caregiver of an elderly patient in Medellin, Colombia. DESIGN: Validation study. SETTING: Primary Care setting in the city of Medellin. PARTICIPANTS: Primary caregiver of dependent elderly patients over 65 years old. PRINCIPAL MEASUREMENTS: Sensitivity, specificity, positive predictive value, and negative predictive value for the different abbreviated Zarit scales, plus performing a reliability analysis using the Cronbach Alpha coefficient. RESULTS: The abbreviated scales obtained a sensitivity of between 36.84 and 81.58%, specificity between 95.99 and 100%, positive predictive values between 71.05 and 100%, and negative predictive values of between 91.64 and 97.42%. CONCLUSIONS: The scale that better determined caregiver burden in Primary Care was the Bedard Screening scale, with a sensitivity of 81.58%, a specificity of 96.35% and positive and negative predictive values of 75.61% and 97.42%, respectively. PMID- 22055917 TI - Cervicitis associated with lateral cervical displacement. AB - Lateral cervical displacement has been recognized as a sign of endometriosis; however, other causes of the finding have not been explored. In our experience, patients without endometriosis are presenting with lateral cervical displacement, mainly towards the left of midline. The common finding in these cases is the presence of cervicitis leading us to hypothesize the role of cervicitis in causing lateral displacement of the cervix. Future research into this area will provide us with a stronger understanding of the role that lateral cervical displacement plays in the development of pelvic pathology and the development of cervical cancer. PMID- 22055918 TI - Transgenic rice accumulating modified cedar pollen allergen Cry j 2 derivatives. AB - In order to create a safe tolerogenic antigen with reduced IgE reactivity, we developed transgenic rice that accumulates in the seed endosperm a sufficient amount of Cry j 2, the cedar pollen allergen, in a restructured form of tail-to head, providing a feasible mucosal allergy vaccine against cedar pollinosis. PMID- 22055919 TI - Comprehensive characterization of two different Nicotiana tabacum cell lines leads to doubled GFP and HA protein production by media optimization. AB - For over two decades, plant cell cultures have been a promising research platform to express recombinant and therapeutic proteins such as hormones, growth factors, full-size antibodies and antigens. Chosen as a good host for manufacturing recombinant proteins, the Nicotiana tabacum L. cv. Bright Yellow 2 (BY-2) cell line has been studied in shake flasks by offline analysis of only a few growth parameters. The objective of this study is to comprehensively characterize the growth of a transgenic BY-2 cell line and to investigate the expression profile of the model protein GFP. Based on the correlations between nutrient consumption, cell growth and product formation, the intention is to improve the standard MS medium. Hereby, multiple growth parameters were analyzed offline and online by using a respiration activity monitoring system (RAMOS). A reproducibly observed shift of the oxygen transfer rate (OTR) could be identified to indicate ammonium depletion in the medium. Concurrent with this ammonium depletion, the total protein concentration began to decrease. After the MS-medium was improved, the GFP concentration nearly doubled. When this improved ammonium enriched medium was applied to another transgenic tobacco cell line similar improvements to the amount of the glycoprotein influenza hemagglutinin (HA) produced by Nicotiana tabacum NT-1 cells could be achieved. Ultimately, this combined offline and online analysis can be successfully used for further cell line characterization and media optimization to improve growth and boost target product formation. PMID- 22055920 TI - Hypergravity effects on myoblast proliferation and differentiation. AB - This study aimed at the investigation of behavior of myoblasts in conditions of altered gravity. C2C12 cells underwent stimulations by different hypergravity intensities (2 h at 5 g, 10 g, and 20 g) in the Large Diameter Centrifuge of the European Space Agency (ESA), highlighting positive effects on both proliferation and differentiation. PMID- 22055921 TI - The effect of swimming lambs and subsequent resting periods on the ultimate pH of meat. AB - The effect of washing lambs in a swim-through bath and subsequent resting periods in the stockyards on the ultimate pH of the M. longissimus dorsi (LD) was studied in 662 animals at a meat export works. There was a linear relationship between the number of times the animals were washed and mean ultimate pH of the LD but there was no statistical association between the duration of the resting period after washing and the ultimate pH. The mean ultimate pH of meat from Perendale lambs from one farm was significantly greater than that recorded from Romney lambs from another farm. It is suggested that such differences may be related to variations in behavioural response and catecholamine secretion in these groups of animals. PMID- 22055922 TI - Electrical stunning of lambs: The effect of stunning parameters and drugs affecting blood flow and behaviour on petechial haemorrhage incidence. AB - Head-to-back electrical stunning of lambs results in speckle bruising, a kind of petechial haemorrhage in muscle fascia, especially when the lamb is tightly restrained. Other factors still appear to modify speckle and some of these are investigated here. There was a significant increase in leg speckle with long stunning duration or high stunning current, but there was little or no increase for the loin. When phenylephrine, a vasoconstrictor, was administered before stunning, there was a reduced speckle compared with the administration of isoproterenol, a vasodilator. The greatest speckle resulted from high currents and isoproterenol administration. These results are consistent with the view that increased blood at speckle sites, i.e. a blush, during the spasm that takes place during stunning, increases speckle. In lambs tranquillized with valium or excited with adrenaline there was no significant difference in speckle for the legs. There was a significant increase of speckle in the loins of valiumtreated lambs. Although increased peripheral blood flow may increase speckle, the effects of stress such as release of adrenaline may reduce this effect. PMID- 22055923 TI - Tissue composition of mechanically deboned pork (MDP). AB - The tissue composition of the mechanically deboned pork produced by a discontinuous pressure system was investigated. By means of quantitative microscopy volume ratios (in terms of volume in volume fractions) of striated muscle, collagenous and elastic connective tissue, bone and cartilage in homogenized samples from eight different producers were determined. Crude protein, fat, calcium and the hard bone residue were determined chemically. In addition, we measured the size of the hard bone particles. The muscle/connective tissue ratio varied from 0.3 to 6.9. The hard bone residue, determined by means of the KOH-method, varied from 0.05 to 0.62%. 0.6% of the bone particles were larger than 3 mm. In addition to chemical analysis we regard quantitative microscopy for the determination of the tissue composition of mechanically deboned pork as imperative for quality control. PMID- 22055924 TI - A note on the influence of rearing environment on meat quality in pigs. AB - Pigs of stress-resistant and stress-susceptible breeds were reared either under intensive conditions in bare concrete pens or extensively under environmentally enriched conditions in an outside paddock. They were slaughtered at either 60 or 90 kg live weight. Rearing environment had no effect on the ability of the pigs to respond to the stress of preslaughter handling based on measurements of adrenal ascorbic acid and plasma cortisol. Neither did it influence initial or ultimate pH or the water holding capacity of the meat. Pigs reared outside had thinner backfat and slightly darker meat. The latter was not attributable to differences in haem pigment concentration. Overall, differences due to rearing environment were slight and not commercially important. PMID- 22055925 TI - Variation among beef breeds in carcass retail value at constant carcass saleable meat content and percentage of higher priced cuts. AB - Data from the single slaughter point trials of the Meat and Livestock Commission's (MLC) beef breed evaluation programme were used to examine the importance of retail value (RV) calculation in breed evaluation trials. The analysis involved a total of 2010 carcasses comprising four production system groups. Sire breeds included Aberdeen-Angus, British Friesian, Charolais, Devon, Hereford, Galloway, Limousin, Lincoln Red, Luing, Simmental, South Devon, Sussex and Welsh Black. RV was computed as the sum of the values of trimmed deboned primal joints expressed as pence per kilogram of carcass weight. 1981 prices from MLC's Retail Prices Survey for England and Wales were used. A model was fitted to the RV data for each of the production system groups with effects for sire breed, year and sire breed * year interaction, and with regression on saleable meat percentage in carcass (SM). The largest difference recorded between sire breeds was 2.1 pence/kg (0.85% of overall mean RV). The pooled within-system residual standard deviation after fitting the model was 1.4 pence/kg. When regression on the percentage of total saleable meat in the higher priced cuts (SMD) was added to the model, the corresponding range and residual standard deviation were reduced to 1.0 and 0.8 pence/kg, respectively. In the circumstances, the calculation of RV would, therefore, make only a minor refinement to the results. PMID- 22055926 TI - Comparison of different agar diffusion methods for the detection of residues in the kidneys of pigs treated with antimicrobial drugs. AB - Residue analyses of the kidneys of twenty-six pigs treated with various antimicrobial drugs 20 h before slaughter and of eleven untreated pigs were performed. The effects of storage temperature of the kidneys, and of sampling location, on the residue analysis were also studied. No method alone was sufficient for the detection of residues. Oxytetracycline residues could be detected at pH 6, dihydrostreptomycin residues at pH 8, and sulphonamide residues if trimethoprim was present in the medium. Chloramphenicol, penicillin G procaine, tylosin and lincomycin residues were not detectable with the methods used. The concentration of ampicillin decreased during the storage of samples at +4 degrees C. Most methods also yielded zones of inhibition for the frozen kidneys from untreated pigs. It seems necessary to use agar media of two different pH values: the addition of trimethoprim to the medium is also needed. The use of fresh pig kidneys, and samples containing both kidney medulla and kidney cortex, is recommended in residue analysis. PMID- 22055927 TI - Studies on the Criollo goat of Northern Mexico: Part 2-Physical and chemical characteristics of the musculature. AB - Groups of castrate male Criollo goats were slaughtered at 12, 16, 20 and 24 kg liveweights after being reared on natural rangeland with concentrate supplementation. After slaughter the carcasses were chilled for 24 h at 2 degrees C, and the total lean was dissected from the left halves of the carcasses. The total lean was subjected to a proximate analysis. M. biceps femoris and M. longissimus dorsi muscles were dissected out of the right halves of the carcasses. Various physical and chemical quality parameters, such as Warner Bratzler shear values and tristimulus colour values, were measured on these muscles in addition to hydroxy proline analysis, for the estimation of collagen content. The moisture content of the total lean decreased steadily with increasing slaughter weight to a level of approximately 76% in the heaviest group. Ash and protein content tended to fall, with intramuscular fat increasing to approximately 16% of the wet tissue weight. The ultimate pH of the two muscles was high in all the slaughter groups, being usually higher than 6.0. Generally, shear values did not change between the slaughter groups in the two muscles. The data indicate that slaughtering castrate male Criollo goats at 24 kg instead of 8 kg does not exert deleterious effects on the parameters of physical and chemical quality investigated. PMID- 22055928 TI - Letter to the editor. PMID- 22055929 TI - High resolution magic angle spinning NMR to investigate ligand-receptor binding events for mass-limited samples in liquids. AB - This work shows that high resolution magic angle spinning (HR-MAS) can be used to elucidate ligand-receptor binding phenomena for mass-limited samples in liquid solution. With respect to conventional 5mm liquid-state NMR probe heads, HR-MAS allows for a considerable reduction (about one order of magnitude) in sample volume requirement, which represents a considerable advantage when working with biological samples present in low amount. More specifically, using a 20-MUL active volume HR-MAS probe head, NMR experiments typically used to describe binding events (e.g. Saturation Transfer Difference, WaterLOGSY, Diffusion Ordered Spectroscopy) were successfully recorded. In fact, contrary to other NMR experiments (e.g. TOCSY), which require special care when performed on liquid samples by HR-MAS, no interferences due to fast sample spinning were observed here. Collectively, the results indicate that HR-MAS allows for a significant mass sensitivity enhancement (a 3-fold increase in signal-to-noise ratio per unit of measuring time and mass was obtained here), hereby improving correspondingly the detection limit of the previously mentioned NMR experiments. More importantly, because MAS removes magnetic susceptibility broadenings in the sample, a good spectral resolution can be easily achieved in HR-MAS even for slightly heterogeneous samples, such as those arising from incomplete purification. PMID- 22055930 TI - Isolation and structural characterization of two tadalafil analogs found in dietary supplements. AB - During routine screenings of two "libido enhancer" dietary supplements using LC MS(n), two compounds were detected that displayed structural similarities to tadalafil. These compounds were isolated from the supplements using high performance liquid chromatography with fraction collection, and were characterized further using accurate mass determination and NMR. "Compound 1" had an m/z of 434 for the [M+H]+ ion, with a corresponding chemical formula of C24H24N3O5. "Compound 2" had an m/z of 432 for the [M+H]+ ion, with a corresponding chemical formula of C25H26N3O4. Although mass spectrometry indicated that these modifications occurred in place of the -CH3 found on the pyrazinopyridoindole-1,4-dione of tadalafil, NMR was required to elucidate the correct configurations of these substitutions. The data obtained using NMR indicated that the structure of the -C3H7O moiety found in Compound 1 was 2 hydroxypropyl, and the -C4H9 in Compound 2 was n-butyl. These new analogs were given the names 2-hydroxypropylnortadalafil and n-butylnortadalafil, respectively. PMID- 22055931 TI - Cardiac magnetic resonance imaging predicts recovery of left ventricular function in acute onset cardiomyopathy. AB - BACKGROUND: In acute onset cardiomyopathy, acute myocarditis is an important cause, as it is associated with a greater likelihood of recovery of cardiac function and its presence may direct specific therapies. Myocarditis can be detected by cardiac magnetic resonance imaging (CMR); however its diagnostic utility and relation to prognosis in acute onset cardiomyopathy are unknown. METHODS: We performed CMR on 61 patients with acute onset cardiomyopathy and a left ventricular ejection fraction (LVEF) <55%. CMR included assessment of myocardial function, relative myocardial oedema, myocardial inflammation (using global relative enhancement [GRE] of the myocardium 4 minutes post Gad-DTPA contrast) and necrosis or fibrosis (with late gadolinium enhancement [LGE]). Patients were followed up at six months to evaluate LVEF, morbidity and mortality. RESULTS: There was a greater improvement in LVEF at follow up in those with myocardial inflammation identified by elevated GRE compared to those without (mean increase 19.2+/-2.5% vs. 6.7+/-1.7%, p<0.001). However, the presence of myocardial oedema or LGE alone was not associated with a greater recovery of LVEF (p=NS for both). Myocardial inflammation in patients with a baseline LVEF<35% was also associated with a greater recovery of LVEF (mean increase 21.5+/-2.9% vs. 9.1+/-3.0%, p<0.01). CONCLUSION: Myocardial inflammation identified by an elevated GRE predicts recovery of LV function in patients with acute onset cardiomyopathy. PMID- 22055932 TI - Vasopressin and oxytocin in plasma of veal calves, sheep and pigs after high voltage electrical stunning. AB - The levels of vasopressin and oxytocin in the plasma of veal calves, sheep and pigs were determined during and after a general epileptiform insult induced by high voltage stunning. Immediately after stunning, a sharp increase in the vasopressin and oxytocin levels was observed in the plasma, followed by a gradual decrease during the next hour. The duration of the general epileptiform insult was correlated (r = 0.79) with the highest measured levels of vasopressin after electrical stunning in the pigs (p <= 0.05). It is suggested that secretion of these neurohypophyseal hormones may affect the memory of aversive experiences during a general epileptiform insult. PMID- 22055933 TI - Carcass characteristics and composition of Brahman, angus and Brahman x Angus steers fed for different times-on-feed. AB - Twenty-five steers of each of three breedtypes (Angus, Brahman and F(1) Brahman x Angus) were sorted by frame size and muscle thickness, assigned to groups (five steers of each breedtype) to be fed for 0, 56, 112, 168 or 224 days, slaughtered and compared for various carcass traits. Steers of each breedtype had similar dressing percentages. Carcasses from all three breedtypes merited similar USDA quality and yield grades; breedtypes differences in quality grade were slight. Differences were found in the fat deposition patterns exhibited by the three breedtypes. Brahman steers tended to deposit more of their total fat as subcutaneous fat early in the feeding period. Angus steers had more (P < 0.05) seam fat as a percentage of carcass weight at all five feeding periods and more (P < 0.05) kidney, pelvic and heart fat at two of the five feeding periods than Brahman steers. Brahman steers had a higher percentage of their separable lean in the muscles of the round than did steers of the other breedtypes. PMID- 22055934 TI - USDA yield grades and various carcass traits as predictors of carcass composition. AB - Twenty-five carcasses from each of three breedtypes (Brahman, Angus and Brahman * Angus) were physically separated into fat, lean and bone. Several muscles from the round and the femur were used to derive equations to predict carcass composition and muscle-to-bone ratio. The femur (as a percentage of the carcass) was shown to predict percentage carcass bone with 90% accuracy. All of the muscles studied were highly related to total carcass lean but the percentage of carcass as M. biceps femoris was the best single muscle indicator of carcass lean of the muscles studied. More variation in carcass lean could be accounted for by a multiple regression equation, involving all four muscles studied, than by any single muscle. M. biceps femoris-to-femur ratio was found to predict carcass muscle-to-bone ratio with a high degree of accuracy. The USDA yield grades were found to be reliable indicators of carcass composition. A two-variable equation involving adjusted fat thickness and biceps femoris accounted for 88.6% of the variation (RSD = 1/.64) in percentage of carcass as separable lean. PMID- 22055935 TI - Comparison of M. longissimus dorsi pigment concentration from implanted and control Angus and Limousin bulls and steers. AB - M. longissimus dorsi total pigment concentration, visual color score and 24-h pH values were evaluated in a 2(3) factorial design that included bulls versus steers, Zeranol implants versus control and Angus versus Limousin comparisons. Bulls had greater total pigment concentration than steers (3.25 versus 2.90 mg/g; P < 0.01) and darker colored lean (P < 0.01). Twenty-four hour pH values did not differ between bulls and steers. Zeranol implanting and breed had no effect on total pigment concentration or visual color score; however, Limousin had higher (P < 0.05) 24-h pH values than Angus. The initial slaughter group (N = 10; average age = 256 days) had 34% less total pigment than the final slaughter group (N = 48; average age = 458 days). The correlation between visual color score and total pigment concentration was -0.65. These results indicate that the darker colored lean from bulls is due in part to an increase in pigment concentration. PMID- 22055936 TI - The antioxidant activities of nitrite and nitrosylmyoglobin in cooked meats. AB - Low concentrations of nitrite (20 mg/kg) caused significant (p < 0.001) inhibition of lipid oxidation, measured by the TBA test, in a cooked muscle system and 50 mg/kg nitrite resulted in a highly significant (p < 0.001) reduction in TBA values. Similar antioxidant effects of nitrite were observed in heated water-extracted pork muscle systems catalysed by 5 mg/g metmyoglobin (Mb) or 5 mg/kg Fe(2+), Cu(2+) or Co(2+). The cured meat pigment, nitrosylmyoglobin per se exhibited significant (p < 0.05) antioxidant effects in pork muscle systems catalysed by Mb or metal ions. Progressive depletion of nitrite occurred during refrigerated storage of heated and unheated nitrite-treated pork muscle, muscle aqueous extract and in systems containing Mb, Cu(2+) ot Co(2+). Nitrite depletion occurred much more rapidly in Fe(2+)-containing systems and nitrite concentration had decreased to 5% of the original concentration immediately after heating. In addition, nitrite caused a significant (p < 0.05) reduction in the concentration of non-haem iron in heated aqueous-extracts of beef muscle, whereas, in nitrite-free extracts, a highly significant (p < 0.001) increase in the concentration of non-haem iron, probably due to heat denaturation of the haem structure with release of iron, was observed. Based on the results of this study, three co-operative mechanisms for the antioxidative activities in meat are proposed: (a) by the formation of MbNO which has antioxidant properties per se, (b) on heating, MbNO forms a stable complex, nitrosylhaemochrome, which blocks the catalytic activity of haem iron and also prevents release of haem iron as non haem iron, which is a highly effective catalyst and (c) nitrite appears to 'chelate' non-haem iron-and possibly copper and cobalt-forming a stable complex, thus inhibiting catalytic activity. PMID- 22055937 TI - Bone substitution materials on the basis of BONITmatrix(r) up-regulate mRNA expression of IGF1 and Col1a1. AB - The aim of this study was to investigate the effects of BONITmatrix((r)) and OSSA NOVA on the expression of growth factors and osteogenic differentiation. For this purpose, the mRNA expression of VEGF, IGF1, IGF2, collagen-1, collagen-2 and MMP8 was analysed in surgically created defects on the crania of adult male rats. Cranial samples were collected after implantation of BONITmatrix((r)) or OSSA NOVA scaffolds for 4 weeks and determinations of gene expression were performed by quantitative RT-PCR. Real-time RT-PCR analyses showed a significantly higher expression of IGF1 in both groups treated with BONITmatrix((r)) and OSSA NOVA compared to untreated controls, whereas type I collagen mRNA expression only increased in BONITmatrix((r)) treated rats compared to controls. No changes in transcript expression of IGF2, VEGF, collagen-2 and MMP8 were detectable between the analysed groups. In conclusion, BONITmatrix((r)) and OSSA NOVA stimulate the expression of growth factor IGF1, but only the granular dosage form is able to stimulate osteoblast differentiation. PMID- 22055938 TI - Coupling of osteogenesis and angiogenesis in bone substitute healing - a brief overview. AB - Similar to osteogenesis and bone repair, the healing and osteogenesis of bone substitutes depend on the osteogenesis-angiogenesis interplay which is controlled by different factors, including VEGF or by hypoxia. A brief review of the process of bone substitute angiogenesis is presented and illustrated by our histological and immunohistochemical findings taken from human biopsies after augmentation with a nanocrystalline synthetic bone substitute. PMID- 22055939 TI - Expression analysis of ADAM17 during mouse eye development. AB - ADAM17 (a disintegrin and metallopeptidase domain 17) is crucial for eye morphogenesis. In this study we analysed the expression pattern of ADAM17 during mouse eye development. ADAM17 expression in adult retina was examined using the reverse transcription-polymerase chain reaction (RT-PCR) and verification of the RT-PCR products by DNA sequencing. Immunohistochemistry was performed to evaluate the ADAM17 expression pattern in mouse eyes at developmental stages of embryonic day (E) 12, E14, E16, E18, postnatal day (P) 0, P1, P4, P7, P14, P 30 and P175 (adult). We detected ADAM17 mRNA in adult retina tissue. ADAM17 protein was expressed in non-pigmented ciliary epithelial cells and in retinal vessels from P7 onwards during eye development. In corneal epithelial cells and endothelium, ADAM17 protein was present from P14 onwards. Although, mice in which the functional ADAM17 gene is significantly reduced develop multiple eye malformations, the expression of ADAM17 is not ubiquitous over the entire eye. Its expression pattern during development suggests that not only TNF-alpha but additional membrane-anchored substrates of ADAM17 play an important role in eye formation. PMID- 22055940 TI - Changes in several constituents during the ripening of 'Chorizo' - A spanish dry sausage. AB - 'Chorizo', a dry fermented sausage marketed in Spain, is traditionally prepared without curing agents or sugars. In order to establish the fermentation process batches A (with added sugars) and B (traditional process) were prepared. pH, carbohydrate disappearance, cured meat pigment formation, free fatty acids (FFA), non-protein nitrogen (NPN) and NH(4)(+) were determined through 100 days of ripening. In batch A, cured meat pigment formation, pH decrease and NPN evolution were greater than in batch B, whereas FFA and NH(4)(+) were similar. Garlic and Spanish paprika added to the mixture introduced significant amounts of fermentable carbohydrates (0.68%) and approximately 16 ppm NO(3)(-). PMID- 22055941 TI - Effect of modified gas atmosphere packaging after dip treatment on myoglobin and lipid oxidation of beef steaks. AB - Fresh beef loin steaks were packaged in atmosphere of: (A) 20% CO(2) + 80% O(2) after dip treatment (dipped in 70% ethanol solution containing 3% l-ascorbic acid and 0.08% dl-alpha-tocopherol), (B) air after dip treatment, (C) 20% CO(2) + 80% O(2) without dip treatment and (D) air without dip treatment (control). After 3,6,9 and 13 days' storage at 4 degrees C, the samples were evaluated for MetMb formation, TBA number and pH. The beef steaks stored in 20% CO(2) + 80% O(2) with or without dip treatment for 13 days maintained an acceptable meat colour. The TBA numbers of samples stored for 13 days in air and 20% CO(2) + 80% O(2) after dip treatment were significantly lower than those of samples without dip treatment. Beef steaks stored for 13 days in 20% CO(2) + 80% O(2) after dip treatment exhibited no change in pH. Data suggested that dip treatment with ascorbic acid and tocopherol solutions before modified gas atmosphere packaging was very suitable for the storage of retail cuts of beef loin steak. PMID- 22055942 TI - Effect of post-mortem storage on Ca(++)-dependent proteases, their inhibitor and myofibril fragmentation. AB - Post-mortem changes in two calcium-dependent proteases, their inhibitor, myofibril fragmentation index (MFI) and collagen (amount and solubility) were studied. Whereas the activity of high Ca(++)-requiring calcium-dependent protease (CDP-II) remained nearly constant throughout post-mortem storage, there was a progressive decrease in the activities of low Ca(++)-requiring calcium-dependent protease (CDP-I) and their specific inhibitor, with the inhibitor being the most susceptible to post-mortem storage. Results indicated that the greatest changes in MFI occur within the first 24 h of post-mortem storage. There were no detectable changes in either total or soluble collagen content with post-mortem storage. Hence, it was concluded that improvement in tenderness resulting from post-mortem storage must be derived from changes in the myofibrils and since CDP I activities paralleled the myofibrillar changes, it seems reasonable to suggest that CDP-I, not CDP-II, plays an important role in the fragmentation of myofibrils and consequently in improvement of meat tenderness resulting from post mortem storage. PMID- 22055943 TI - Investigation of the levels of N(tau)-methylhistidine in a range of pork and chicken meats. AB - Protein bound N(tau)-methylhistidine (N-MeHis) has been suggested as an index for the estimation of muscle (meat) protein in meat and meat products. This paper examines the level of N-MeHis in a range of five pork and two chicken prime cuts together with five other pork and one chicken manufacturing cuts of meat. It is shown that whilst similar levels are present in the prime cuts there is a considerable variation in those found in the other cuts. The average N-MeHis level, expressed as MUg/g fat-free connective tissue-free (FFCF) meat, was 116 for pork, 116 for chicken breast and 129 for chicken leg. From the other pork cuts investigated, only two gave levels similar to that for prime pork whilst the rest were all considerably lower. Chicken MRM gave an N-MeHis level 75% of that for (combined) leg and breast meat. Since all these meat cuts are regarded as legitimate meat materials in the UK, there would appear to be serious drawbacks to the use of N-MeHis as a quantitative index of lean meat. PMID- 22055944 TI - Effect of electrical stimulation and temperature on biochemical changes in beef muscle. AB - The effect of low voltage electrical stimulation and storage temperatures of 2, 15 and 25 degrees C on biochemical changes in M. sternocephalicus from beef carcasses was studied. It was shown that electrical stimulation accelerated the glycolytic processes resulting in an immediate increase in muscle lactate and about 30% reduction in ATP. Combination of stimulation and 15 or 25 degrees C temperature further increased the changes with ATP, reaching 2 MUM/g muscle in about 2 h post mortem. At 2 degrees C, the biochemical changes were slow. By ensuring that the muscle temperatures in low voltage stimulated carcasses do not fall below 15 degrees C for 2 to 3 h, this should provide favorable conditions for depletion of ATP and glycogen and the prevention of cold shortening at chilling. PMID- 22055945 TI - Effect of acid decontamination of beef subprimal cuts on the microbiological and sensory characteristics of steaks. AB - Beef strip loins were decontaminated by spraying with solutions of various food grade acids (1.0% lactic acid, 1.0% acetic acid and an acid mixture containing 1.0% lactic acid, 2.0% acetic acid, 0.25% citric acid and 0.1% ascorbic acid) followed by vacuum packaging and storing at 4 +/- 1 degrees C. Initially and at days 3 and 6 of display in polyvinyl chloride (PVC) film, aerobic plate counts (APCs) of steaks fabricated from the acid treated loins that were stored for 0, 14, 28, 42, 56, 70 and 84 days were not significantly different (P > 0.05) from the APCs of steaks fabricated from control loins. PMID- 22055946 TI - Variations in the tensile adhesive strength of meat-myosin junctions due to test configurations. AB - A model system of two thick slices of beef M. semitendinosus stuck together with a crude myosin preparation and cooked to 80 degrees C for 1 h has been used to show the effects of testing configuration on the tensile adhesive strength (TAS) of the meat-myosin junction. TAS decreased with increasing cross-sectional area in a square cross-sectional geometry, but increasing just one dimension of a rectangular cross-section resulted in smaller, often insignificant, decreases in TAS. A hypothesis based on differences in stress distributions over the area of the adhesive joint was proposed to explain this. TAS was found to increase with increasing deformation rate, in accordance with the usual behaviour of viscoelastic materials. TAS was found to be approximately three times higher when muscle fibres in both the meat pieces forming the joint were at right angles to the junction than when one or both meat pieces contained fibres running parallel to the adhesive junction; this latter orientation, being the weaker, is therefore proposed to be the orientation that determines the initial fracture of a meat product, hence its textural properties. PMID- 22055947 TI - Anabolic agents in beef production: Effects on muscle traits and meat quality. AB - The effects of combined oestradiol and trenbolone acetate implants have been investigated. Meat tenderness, juiciness and flavour were assessed by trained taste panelists and 16 variables related to muscle biochemistry and composition and ageing kinetics parameters were analysed on Longissimus dorsi and Triceps brachii caput longum muscles from 24 months old treated and control Charolais steers. Increases in carcass weight and mean daily weight gain, generally observed following such treatment, were confirmed. Furthermore, meat quality traits and ageing rate were significantly correlated with muscle typing parameters. Factorial discriminant analysis of data revealed that muscle typing (isomyosin 3 content) and composition (dry matter and lipid content) as well as NRM relaxation time of meat water (T2b) and ageing rate were the most affected by treatment. In addition, the hormone effect appeared to be muscle dependent. PMID- 22055948 TI - Effect of citric acid, citrate and slight a(w) decreases on the bacteriological stability of Hague liver sausage. AB - Combinations of citric acid and citrate, with several carbohydrates and KCl, were tested in a canned Hague liver sausage model for their antimicrobial properties. pH values for the test products ranged from 5.38 to 6.48; a(w) values varied from 0.960 to 0.977. Before pasteurization, the sausage doughs were contaminated with mixtures of bacterial spores. Since the bacteriological stability sometimes appeared to be considerably improved, heated packages were challenged by incubation at 20 degrees and 30 degrees C; some of them for up to 2 years. Incubated packages from the standard formulation spoiled at 30 degrees C within 3 days. Starting from this point, products with a variable, but increased, bacteriological stability were obtained. For the best stabilized batches, first symptoms of spoilage were observed after periods of incubation at 30 degrees C, ranging from 49 to 150 days. Combinations of pH and a(w) values which can be relied upon to yield stable products consistently, cannot be derived from the accumulated data. Citric acid appeared a far more effective stabilizer than its salt. If we regard the undissociated citric acid concentration for these products (a(w) 0.960-0.972) as a significant parameter, values above approximately 13 MUmkg(-1), yielded products with remarkable bacteriological stability. PMID- 22055949 TI - The effects of spray-chilling carcasses on the shrinkage and quality of beef. AB - After slaughter, alternate beef carcass sides (left, right) were allocated to an intermittent spray-chilling cooling treatment using water (4 cycles per hour; 60 s/cycle) and conventional air chilling (1-2 degrees C; air velocity 0.5 m/s), or conventional air chilling only. Experiments 1, 2, and 3 (n = 19, 26 and 16 carcasses) involved spray-chilling for 4, 8, 12 h in shrouded sides, whereas experiment 4 (n = 16 carcasses) involved 8 h of spray-chilling in unshrouded sides. At 24 h post-slaughter all sides were ribbed (12 13 th ribs ), and assessed for meat and fat colour. Half the treatment and control sides in each experiment were aged for 6 days, while the boneless ribs and inside rounds were removed from the remaining sides, vacuum packaged and held for 6 days. After 6 days of storage, retail packs of rib steaks and round roasts were prepared and assessed for colour and drip losses over a 4-day period. Spray-chilling significantly reduced carcass shrinkage at 24 h post slaughter in experiments 1-4 by 0.48, 0.69, 0.89 and 1.48%, respectively. After 6 days of cooler storage, spray-chilling significantly reduced carcass shrinkage in experiments 3 and 4 only (0.47 and 0.94%). Weight and drip losses for vacuum packaged ribs and inside rounds were not influenced by spray-chilling over 6 days of storage. Spray chilling had no influence on rate of pH decline, but reduced loin and round muscle temperatures by 1-2 degrees C. Loin eye muscle colour and shear force were not affected by treatment, but in experiments 2, 3 and 4, fat colour was significantly lighter in spray-chilled compared to conventionally chilled sides. Colour changes and drip losses in retail packs over 4 days for rib steaks and round roasts were not related to spray-chilling. It was concluded that spray chilling could provide a moderate reduction in carcass shrinkage during cooling without having a detrimental influence on muscle quality. PMID- 22055950 TI - Microbiological evaluation of navy bean flour and its blend with retail ground beef. AB - Sterile water suspensions of navy bean flour (NF) were used as a model medium on which the growth of eight microorganisms important for food hygiene and technology was evaluated. Almost all microorganisms grew better on model mediums with 10 and 15% of NF than on the nutrient broth (control). Retail ground beef with and without 5, 10 and 15% addition of NF was wrapped with plastic film and stored at 4 degrees C. Aerobic plate count, psychrophiles, coliforms and yeasts and molds were assessed after 0, 3 and 6 days. Navy bean flour added to ground beef had a significant effect only on aerobic plate count. Growth of psychrophiles, coliforms, yeasts and molds was not affected by addition of NF. Microflora of retail ground beef-NF blends mainly consisted of Lactobacillus spp., while other genera of bacteria were found in smaller numbers. The pH of blends increased in proportion to the level of NF added and was significantly higher in comparison with retail ground beef alone, but decreased during storage due to the large amount of lactic acid bacteria. PMID- 22055951 TI - Influence of PSE pork on the quality and economics of cooked, cured ham and fermented dry sausage manufacture. AB - PSE pork (pH(1) <= 5.8) and non-PSE pork (5.8 < pH(1) <= 6.4) were used for cooked, cured ham production and, with beef, in a 48 52 mixture for fermented dry sausage manufacture. Technological yields of PSE and non-PSE hams were, respectively, 94.0 and 105.9% which corresponded to 5.0 FMK/kg loss for the PSE ham compared to the non-PSE ham. In addition, cooked PSE ham had a poorer organoleptic quality compared to non-PSE ham. However, PSE meat could be mixed with normal meat for the production of fermented dry sausage without quality defects. PMID- 22055952 TI - The effect of stocking density during 4 hour transport to slaughter on behaviour, blood constituents and carcass bruising in Friesian steers. AB - The aim of this work was to assess the response of Friesian steers to road transportation at low, medium and high (ca 200, 300 and 600 kg/m(2)) stocking densities in terms of physiology, behaviour and carcass bruising. Stocking density was determined by adjusting the number of animals per pen (3 runs) or by adjusting pen size (3 runs). Plasma cortisol and glucose increased (P < 0.001) with stocking density, as did plasma CK activity (P < 0.001) and carcass bruising (P < 0.01) both of which indicate muscle damage. At constant stocking density stress increased with pen location towards the tail of the truck, as reflected by a significant increase in plasma cortisol. Stocking density influenced standing orientation within the truck. At low stocking density animal movement was unrestricted and the preferred orientation was standing parallel to the direction of travel; there was a strong bias against diagonal orientations. Losses of balance were associated with specific driving events, notably braking and cornering. Minor losses of balance were observed at all stocking densities, but major losses of balance including animals going down underfoot were associated with high density. When an animal went down at high stocking density it did so involuntarily and was sometimes trapped down, destabilizing other members of the group in a domino effect. Exploratory, sexual and aggressive behaviours were inhibited at high stocking density, with the exception of mounting and pushing, which increased in frequency with stocking density. It was concluded that the high stocking density adversely affected animal welfare and lowered carcass quality when compared with the medium and low stocking densities. PMID- 22055953 TI - Differentiation between fresh beef and thawed frozen beef. AB - In order to prevent meat retailers offering thawed, imported frozen beef as fresh domestic beef, the method of Gottesmann and Hamm for differentiating between fresh and frozen/thawed meat is recommended. The principle of this method is based on the fact that freezing and thawing of meat results in a release of the enzyme beta-hydroxyacyl CoA-dehydrogenase (HADH) from the mitochondrion into the sarcoplasm; an elevated HADH activity in the muscle press-juice indicates freezing and thawing of tissue. The HADH colour test of Gottesmann and Hamm was modified by replacing the electron-transmitter meldolablue by resazurin which results in a much higher colour stability after reaction with fresh meat extracts. PMID- 22055954 TI - Electrical stimulation and meat texture-A response to preliminary reports on the toughening effect of electrical stimulation. PMID- 22055955 TI - Electrical stimulation and meat texture: A reply to comments by E. Dransfield and D. J. Etherington. PMID- 22055956 TI - Obituary. PMID- 22055957 TI - Fat partition and distribution in the carcasses of cattle, sheep and pigs: A review. AB - Results from recent Meat and Livestock Commission studies on fat partition and distribution are reviewed, together with those from other published work. Attention is drawn to the commercial importance of these characteristics and to the fact that little is known about their variability, in particular the extent to which fat partition is influenced by environmental factors. Information available from breed trials indicates that there is substantial genetic variation for all three species in the partitioning of fat between depots, although there is less variation in the way in which a given weight of subcutaneous fat or intermuscular fat is distributed through the carcass. PMID- 22055958 TI - Influence of temperature on the rate of post-mortem metabolism and water-holding capacity of bovine neck muscles. AB - Strips of forty bovine neck muscles were placed at temperatures in the range -1 degrees to +30 degrees C within 45 min of slaughter and stored for up to 24 h. Strips were taken at various times during storage and assayed for pH, 'R' value (degree of transformation of ATP to IMP) and ATP concentration. The water-holding capacity (WHC) of the intact muscle was compared with the WHC of a salted muscle homogenate prepared at each sampling time. The rate of pH fall post mortem was relatively low around +5 degrees C and increased at lower or higher temperatures. ATP concentration showed a delay phase dependent on storage temperature and a subsequent rate of depletion which was also temperature dependent. The patterns of change in WHC of the muscle samples and the salted homogenates differed, the former showing a rapid fall to a fairly steady level shortly after initiation of storage, the latter showing no appreciable change until the onset of rigor. It is suggested that salting meat at any time prior to the onset of rigor will confer improved WHC and that the temperature of storage post mortem should be chosen to induce low rates of ATP turnover so as to prolong the feasible delay between slaughter and salting. PMID- 22055959 TI - Hot deboning beef with and without electrical stimulation. AB - Two hot deboning procedures for producing vacuum packed primal beef joints were compared with conventional side chilling followed by cold deboning. Cold shortening toughness was avoided in the hot procedures either by a delay before chilling or by electrical stimulation of the carcass. Overall evaporative losses were 0.6% with hot deboning and 1.9% with cold deboning. Hot deboning reduced drip loss but the effect was smaller after electrical stimulation. The colour of large muscles which cool unevenly on the side was more uniform after hot deboning, but again the improvement was smaller after electrical stimulation. There was no difference in bacterial contamination or growth on hot and cold deboned meat, and instrumental and sensory assessments confirmed that eating quality was similar for all three treatments. PMID- 22055960 TI - Blood splash in lambs-a preliminary study using the one-stage prothrombin time test. AB - Lambs from a flock in which a high incidence of blood splash had been detected were examined using the one-stage prothrombin test. For comparison lambs from a commercial slaughter line were also examined. All the affected lambs and 35.4% from the slaughter line had extended prothrombin times, and a relationship between extended prothrombin times and the occurrence of blood splash was established. Investigation of the pastures grazed by the affected flock showed the presence of coumarin producing plants and grasses. Some coumarin drugs prolong one-stage prothrombin times, and more importantly, induce capillary fragility, thus predisposing animals to blood splash. PMID- 22055961 TI - Quantifying changes in tenderness during storage of beef. AB - An exponential decay equation was used to quantify changes in beef toughness during storage at constant temperatures between 0 degrees and 20 degrees C. Temperature had the greatest effect on tenderising rate-thirty-two times that due to animals and ten times that due to muscles which were M. longissimus dorsi, M. psoas major and M. semitendinosus. A common rate constant, derived at each temperature, showed that an increment in rate produced by a 5 degrees C rise in storage temperature was then detectable and that the enthalpy of activation (DeltaH(*)) was 76 kJ/mole. Toughness constants differed most between muscles. PMID- 22055962 TI - Tenderising in M. longissimus dorsi of beef, veal, rabbit, lamb and pork. AB - The decrease in toughness of M. longissimus dorsi with storage time at 1 degrees C was effectively described by an exponential decay equation. The average rate constant for beef, veal and rabbit was 0.17 whilst that for lamb was 0.21 and that for pork, 0.40 days(-1). However, the rate constants were not significantly different due to variations both within muscles and between animals. On average, 50% of the tenderising occurred in 2 days for pork and in 4.2 days for beef, veal and rabbit, and 80% in 4.9 and 9.5 days, respectively. At the completion of tenderising, beef and rabbit were the toughest and pork the most tender, whilst the greatest tenderising occurred in beef and lamb. PMID- 22055963 TI - Isolation and partial characterisation of bovine rumen myosin. AB - Myosin was isolated from rumen muscle and purified by DEAE Sephadex A-50 chromatography. The purified myosin gave only two bands on SDS gel electrophoresis, one corresponding to the heavy chain of 210 000 D and the other corresponding to a light chain of 17 000 D. The pH optimum of the rumen myosin ATPase activity was found to be at 7.6; and at pH 9.1, there was no detectable activity. The ATPase activity of the rumen myosin was found to be lower than that of the skeletal myosin. Since it is known that the light chains are located on the globular head of the myosin molecule, where the ATPase activity is found, the lower rumen myosin ATPase activity may be due to the absence of certain light chains that are commonly found in the skeletal myosin. The rumen myosin also had a lower basic amino acid content and a lower ratio of basic to acidic amino acids than the corresponding skeletal muscle counterpart. PMID- 22055964 TI - Fat deposition in a double-muscled steer. AB - A homozygous double-muscled steer was full fed a high-energy ration for approximately 18 months to assess its potential for fat deposition. After slaughter, the carcass possessed modest quantities of intramuscular fat. The fat thickness at the 12th rib was 2.4 cm and the carcass contained about 3.5% kidney, heart and pelvic fat. The adipose tissue appeared physiologically normal, as its composition of total lipids and individual fatty acids was comparable to that published for non-DM market cattle. In addition, adipose cellularity was comparable to non-DM cattle of similar fatness and weight, indicating that at least some double-muscled cattle have a potential for adipose development comparable to non-double-muscled animals. PMID- 22055965 TI - Factorial validity and invariance of the Life Satisfaction Index in older people across groups and time: addressing the heterogeneity of age, functional ability, and depression. AB - In the last decades, extensive research efforts have been directed at exploring life satisfaction in old age, and the Life Satisfaction Index A (LSIA) scale, developed by Neugarten et al. in the 1960s, is one of the most commonly used instruments. However, studies have focused on predicting and comparing changes in people's life satisfaction without testing if the LSIA instrument is equally valid for different subgroups of people. The present study investigated the underlying dimensions of the LSIA in a Swedish population (n=1402) of people 60 96 years of age. The study also examined factorial invariance across age, gender, functional ability and depression during a six-year period. The results showed that while a five-factor solution of the LSIA did not exhibit an acceptable fit to the data, a three-factor solution did show a close fit. The two three-factor models that demonstrated the best fit showed invariance across gender and across time, but noninvariance across groups with different levels of reduced functional ability, depressive symptoms and age. These findings suggest that the psychometric properties of life satisfaction instruments like the LSIA need to be taken into consideration before drawing conclusions about life satisfaction when comparing older people of different ages and with different depression and function levels. PMID- 22055966 TI - A supportive home visit program for older adults implemented by non professionals: feasibility and effects on physical performance and quality of life at one year--a pilot study. AB - Knowledge of supportive home rehabilitative procedures is needed to improve the independent home training and psychosocial wellbeing of older people. The primary focus of this study was to assess the feasibility of a home visit program involving the use of non-professional home rehabilitation assistants (HRAs) support among elderly. The secondary objective was to investigate the effects to physical performance and health-related quality of life (HRQL) of older people. A controlled intervention study was implemented at two war veterans' rehabilitation centers in Finland. The study included 22 long-term unemployed people aged 26-58 years, who were educated in HRA tasks and 417 community-dwelling persons aged 65 99 years, who participated in 10-28 days of inpatient rehabilitation. The intervention group (IG) received 10-14-month physiotherapist-supervised HRA home visit program. The control group (CG) received no home visit intervention. Additional information was collected to assess the feasibility of the intervention. Structured interviews were carried out. Physical performance was evaluated through several validated tests, pain with the Visual Analog Scale (VAS), and HRQL with the Leipad questionnaire. The HRAs adopted their supporting role through the social activation of the rehabilitees and continued to study to become practical nurses. At 10-14 months, HRQL among women (p=0.029) and chair rising among men (p=0.028) improved in the IG but declined in the CG. The supportive home visit program was feasible and improved the HRQL in women and chair rising in men. This model could motivate long-term unemployed people to educate themselves. PMID- 22055967 TI - Integrating novel therapies into the treatment of sarcoma: a multidisciplinary approach--introduction. PMID- 22055968 TI - Appraising the current role of chemotherapy for the treatment of sarcoma. AB - Sarcomas are a heterogeneous group of relatively rare mesenchymal neoplasms. They can be grouped into two general categories: soft tissue sarcoma (STS) and primary bone sarcoma, which are treated differently. Because sarcomas are relatively rare and complex with a wide variety of different histopathologic subtypes, evaluation by multidisciplinary teams who have expertise in the field is recommended. Treatment guidelines for the use of chemotherapy in patients with STS and bone sarcoma have been published by the National Comprehensive Cancer Network. The role of adjuvant chemotherapy in resected STS remains controversial. Although chemotherapy improves disease-free survival, the long-term overall survival benefit remains unproven. Chemotherapy is typically used as palliative treatment for most subtypes of metastatic STS. In contrast, chemotherapy has a proven role in the treatment of primary bone tumors and Ewing sarcoma, but it has not demonstrated efficacy in the treatment of chondrosarcoma. The standard chemotherapy regimens used in sarcoma are associated with significant toxicity, including long-term complications. Less intense and less toxic regimens are the focus of ongoing clinical research. Newer cytotoxic agents with an improved safety profile, such as trabectedin and palifosfamide, are currently in development. Future research needs to focus on identification of subpopulations of patients that are most likely to benefit from chemotherapy. PMID- 22055969 TI - Clinicopathologic considerations: how can we fine tune our approach to sarcoma? AB - Bone and soft tissue sarcomas are an uncommon and sundry group of solid tumors traditionally categorized together according to their presumed mesenchymal differentiation. They are histologically, behaviorally, and genetically diverse, and their pathogenesis is poorly understood. Moreover, treatment options are limited, with surgical resection continuing to provide the only possibility of cure in many cases. However, there has been tremendous progress in the last decade in understanding the behavior and molecular pathogenesis of sarcoma, which may ultimately lead to more effective therapy and prognostication for these rare malignancies. In this article, we address the histologic and molecular classification of sarcomas, with emphasis on the increasing role of molecular diagnostics in both classification and prognostication. In addition, we review recent advances in the understanding of critical cell signaling pathways involved in this group of malignancies, and how this knowledge relates to the potential role of newer targeted therapies in sarcoma treatment. The role and rationale for grading and staging of sarcomas is discussed, as well as more recent advances in the development of prognostic nomograms, based on clinical and histopathologic findings. Finally, we conclude with a discussion of the importance of multidisciplinary care, with integration of histologic, molecular, radiographic, and clinical data in the management of sarcoma. PMID- 22055970 TI - Targeted agents for sarcoma: is individualized therapy possible in such a diverse tumor type? AB - A wide variety of cytogenetic abnormalities and molecular pathways have been implicated in the pathogenesis of sarcoma, and significant progress has been made in the past decade toward identifying potential therapeutic targets. However, apart from gastrointestinal stromal tumors (GISTs) and dermatofibrosarcoma protuberans (DFSP), little progress has been made toward translating that knowledge into effective therapeutic strategies. The identification of activating KIT mutations in the majority of GISTs was a defining moment that led to the first effective targeted therapy for sarcoma, and the subsequent use of imatinib mesylate has revolutionized the treatment of GISTs. Beyond imatinib, the most promising agents to date--and the agents most extensively studied--are the multitargeted tyrosine kinase inhibitors. Several other classes of agents have also shown some activity in soft tissue sarcomas, including mammalian target of rapamycin inhibitors, inhibitors of growth factor receptors, histone deacetylase inhibitors, agents that modulate the p53 pathway, inhibitors of molecular chaperone proteins (eg, heat shock protein 90 [Hsp90]), and other signal transduction inhibitors. Despite a large number of completed and ongoing phase II studies, few agents have moved to phase III testing, and much work remains to be done to fully validate the identified targets and determine the optimal treatment strategy. Ongoing studies are exploring a wide range of combination strategies. This review will highlight some of the emerging targeted therapies that appear to hold promise and may eventually contribute to improved systemic therapy for sarcoma. PMID- 22055971 TI - Prospects for designating Alzheimer's disease research a national priority. AB - This editorial evaluates the prospects of the National Alzheimer's Project Act (NAPA) succeeding to shape public policies that would substantially increase national expenditures for research on Alzheimer's disease. The essay identifies, in the context of 30-year history, some of the difficult challenges the NAPA Advisory Council must address and offers specific recommendations for an action plan by the Secretary, Department of Health and Human Services (DHHS). PMID- 22055972 TI - Videoconference diagnosis and management of Choctaw Indian dementia patients. AB - BACKGROUND: This study reports a 5-year experience using videoconference (VC) technology in diagnosing and treating adult members of the Choctaw Nation with symptoms or complaints of cognitive impairment. METHODS: Patients were given the option of a VC session or a face-to-face evaluation in the clinic. Before their VC session, patients underwent neuropsychological testing, Clinical Dementia Rating, Geriatric Depression Scale and Neuropsychiatric Inventory, brain computed tomography, and routine blood tests. Physical observations made by VC included eyesight, hearing, facial expression, gait and station, coordination, tremor, rapid alternating movements, psychomotor activity, and motor tests of executive function. Cogwheeling and rigidity were tested by our on-site nurse, who also obtained vital signs as indicated. RESULTS: Between January 2005 and March 2010, there were 47 clinics, 171 visits, and 85 unique patients. There were 52 new evaluations and 119 follow-up visits. The number of visits ranged from one to eight and the length of follow-up from 1 month to 4.5 years. The no-show rate for all VC sessions in 2009 was 3%, and only two subjects in 5 years refused further VC visits. CONCLUSION: Once cultural barriers are dealt with, VC-based diagnosis and treatment of adults with cognitive disorders who live in remote areas is feasible and well accepted by patients and families. PMID- 22055973 TI - Predictors of suicide in patients with dementia. AB - BACKGROUND: Assessing predictors of suicide and means of completion in patients with dementia may aid the development of interventions to reduce risk of suicide among the growing population of individuals with dementia. METHODS: This national, retrospective, cohort study used data from the Department of Veterans Affairs (fiscal years 2001-2005). The sample included patients >=60 years old diagnosed with dementia (N = 294,952), of which 241 committed suicide. Potential predictors of suicide were identified using logistic regression. Suicide methods are also reported. RESULTS: Increased risk of suicide was associated with white race (OR: 2.4, 95% CI: 1.2, 4.8), depression (OR: 2.0, 95% CI: 1.5, 2.9), a history of inpatient psychiatric hospitalizations (OR: 2.3, 95% CI: 1.5, 3.5), and prescription fills of antidepressants (OR: 2.1, 95% CI: 1.6, 2.8) or anxiolytics (OR: 2.0, 95% CI: 1.5, 2.7). Nursing home admission was associated with lower suicide risk (OR: 0.3, 95% CI: 0.1, 0.8). Severity of medical comorbidity did not affect risk of suicide. Sensitivity analysis indicated that the majority of suicides occurred in those who were newly diagnosed with dementia. Firearms were the most common method of suicide (73%) used. CONCLUSIONS: Given the higher rate of suicide in those receiving treatment for psychiatric symptoms and the high proportion that died using firearms, closer monitoring and assessment of gun access may be an important part of initial treatment planning for older male patients with dementia, particularly those with symptoms of depression or anxiety. PMID- 22055974 TI - Presenilin enhancer-2 gene: identification of a novel promoter mutation in a patient with early-onset familial Alzheimer's disease. AB - gamma-Secretase proteins complex cleaves the amyloid precursor protein (APP) to generate amyloid-beta (Abeta) peptides. Considerable evidence suggests that alterations in genes encoding these proteins exert their influence on the pathogenesis of familial Alzheimer's disease (FAD). Presenilin enhancer-2 gene (PEN-2) is a necessary component of the gamma-Secretase complex. Recently, it has been shown that PEN-2 mutations could be involved in Alzheimer's disease (AD). We performed a mutational screening of all PEN-2 coding and promoter regions in a FAD cohort derived from Southern Italy. Four hundred and fifty-two subjects (FAD: 97; CONTROLS: 355) were recruited for this study. We identified for the first time in a key region necessary for the promoter activity a novel 3 bp deletion in a subject with early-FAD. Our genetic data demonstrate that the mutant allele may influence the transcriptional activity of the PEN-2 gene. Although the effective role of the PEN-2 promoter deletion in AD is not entirely clear, these findings might lead to more studies on its functional and genetic role. PMID- 22055975 TI - Long-term progression of Alzheimer's disease in patients under antidementia drugs. AB - BACKGROUND: Patients with Alzheimer's disease (AD), even in the presence of symptomatic relief from medical intervention, face a persistent worsening of cognitive decline and performance in activities of daily living. Data regarding the long-term disease progression outside of therapeutic trials are lacking. We examined the effects of standard of care for AD patients on the prognosis of the disease in a real-life study over a 4-year period. METHODS: A total of 686 patients with mild-moderate AD were enrolled in 16 memory clinics (REseau sur la maladie d' Alzheimer FRancais [REAL.FR] cohort) and followed up twice annually with tools used in therapeutic trials (Mini-Mental Status Examination, Alzheimer Disease Assessment Scale-cognitive subscale [ADAS-cog]: cognitive function, Clinical Dementia Rating: dementia severity, Activity of Daily Living [ADL]: incapacities, NeuroPsychiatric Inventory: neuropsychiatric symptom). RESULTS: More than 90% of the patients used AD-specific medication over 4 years. Patients lost on average 2.4 points per year on the Mini-Mental Status Examination and gained 4.5 points on the ADAS-cog. ADL and NeuroPsychiatric Inventory scores became significantly worse over time. Incidence of incapacities for ADL and worsening of neuropsychiatric symptoms were 52.5 (95% confidence interval [CI]: 47.7-57.4) and 51.1 (95% CI: 46.2-56.1), respectively. Rates of mortality and institutionalization were 7.4 (95% CI: 6.2-8.5) and 13.4 (95% CI: 11.7-15.1). In all, 17% of patients in mild stage at baseline (Clinical Dementia Rating = 0.5) did not experience a major event (functional disabilities, neuropsychiatric symptoms, or death) over a 4-year period. CONCLUSIONS: As compared with previous surveys, the current study shows slower rates of decline in AD patients. The present data also underline the high level of variability of disease progression among AD patients. Outcome measures commonly used in clinical trials will need to take into account the recent changes in the prognosis of the disease. PMID- 22055976 TI - The measurement of everyday cognition: development and validation of a short form of the Everyday Cognition scales. AB - BACKGROUND: This study describes the development and validation of a shortened version of the Everyday Cognition (ECog) scales [Tomaszewski Farias et al. Neuropsychology 2008;22:531-44], an informant-rated questionnaire designed to detect cognitive and functional decline. METHODS: External, convergent, and divergent validities and internal consistency were examined. Data were derived from informant ratings of 907 participants who were either cognitively normal, had mild cognitive impairment (MCI), or had dementia. RESULTS: Twelve items were included in the shortened version (ECog-12). The ECog-12 strongly correlated with established functional measures and neuropsychological scores, only weakly with age and education, and demonstrated high internal consistency. The ECog-12 showed excellent discrimination between the dementia and normal groups (area under the receiver operator characteristic curve = 0.95, CI = 0.94-0.97), and showed promise in discriminating normal older adults from those with any cognitive impairment (i.e., MCI or dementia). Discrimination between the MCI and normal groups was poor. CONCLUSIONS: The ECog-12 shows promise as a clinical tool for assisting clinicians in identifying individuals with dementia. PMID- 22055977 TI - Functional deficits among patients with mild cognitive impairment. AB - BACKGROUND: Diagnostic criteria for mild cognitive impairment (MCI) include no significant functional decline, but recent studies have suggested that subtle deficits often exist. It is not known whether these differ by MCI type. We investigated the level and type of functional impairment among patients with MCI. METHODS: We studied 498 patients, evaluated at the Alzheimer's Disease Research Centers of California between 2006 and 2009, who had multidisciplinary evaluations by experts, including neurologic examination and neuropsychological testing. Patients were diagnosed with MCI and subtype was determined using cognitive domain scores. In a cross-sectional descriptive study, we examined whether functional impairment differed by MCI subtype, using the Blessed Roth Dementia Rating Scale (range: 0-17, higher scores indicating more impairment). RESULTS: Among the participants, the mean age was 75.4 years, 50.7% were women, and 81.7% were white. Patients with amnestic- (n = 392, 78.7%) and nonamnestic type (n = 106, 21.3%) MCI had similar total Blessed Roth Dementia Rating Scale (1.6 and 1.5, respectively; P = .84) and Mini-Mental State Examination (26.5 and 26.7, respectively; P = .60) scores. Patients with amnestic MCI were more likely to have difficulty in remembering lists and recalling recent events (P < .05 for both) and less likely to have difficulty in eating and with continence (P = .01 for both), as compared with those with nonamnestic MCI. CONCLUSIONS: Despite the MCI diagnostic criteria suggesting no functional impairment, our results indicate that patients with MCI experience mild functional deficits that vary according to the type of MCI. PMID- 22055978 TI - Countrywide strategic plans on Alzheimer's disease: developing the framework for the international battle against Alzheimer's disease. AB - As the world's population ages, countries must prepare for the significant impact Alzheimer's disease will have on their health systems, their economies, and their citizens. In anticipation of major global demographic changes, many countries in the G-20 since 2000 have begun to develop and enact plans to address Alzheimer's disease as a national priority. However, even with nearly half of these participating countries having plans in place, there has been little research done to quantify the value of enacting a countrywide plan on this disease. In this review, we summarize recent national plans (from the year 2000 and beyond) and any results stemming from their respective recommendations and activities. PMID- 22055979 TI - Studies of 6Li-NMR properties in different salt solutions in low magnetic fields. AB - In this article we report the longitudinal relaxation times (T(1)) of various (6)Li salts ((6)LiI, (6)LiCl and (6)LiNO(3)) in D(2)O and H(2)O, measured in low magnetic fields (B(0)=3.5mT). This investigation serves the purpose of clarifying the relaxation behavior of different (6)Li solutions and different concentrations. The measurement were undertaken to establish a framework for future applications of hyperpolarized (6)Li in medical imaging, biological studies and investigations of lithium ion batteries. Time will pass during the transport of hyperpolarized lithium ions to the sample, which leads to a polarization loss. In order to store polarization as long as possible, it is necessary to examine which (6)Li salt solution has the longest relaxation time T(1). Longitudinal relaxation times of (6)Li salts in D(2)O and H(2)O were investigated as a function of concentration and the most extended T(1) was found for (6)LiI in D(2)O and H(2)O. In agreement with the theory the relaxation time T(1) of all (6)Li salts increase with decreasing concentration. In the case of (6)LiI in H(2)O an inverse behavior was observed. We assume that the prolonged T(1) times occur due to formation of (6)LiOH upon the solution of (6)LiI in H(2)O, which settles as a precipitate. By diluting the solution, the precipitate continuously dissolves and approaches T(1) of (6)LiOH (T(1)~28s), leading to a shorter T(1) relaxation time. PMID- 22055980 TI - Time displacement rotational echo double resonance: heteronuclear dipolar recoupling with suppression of homonuclear interaction under fast magic-angle spinning. AB - We have developed a novel variant of REDOR which is applicable to multiple-spin systems without proton decoupling. The pulse sequence is constructed based on a systematic time displacement of the pi pulses of the conventional REDOR sequence. This so-called time displacement REDOR (td-REDOR) is insensitive to the effect of homonuclear dipole-dipole interaction when the higher order effects are negligible. The validity of td-REDOR has been verified experimentally by the P 31{C-13} measurements on glyphosate at a spinning frequency of 25 kHz. The experimental dephasing curve is in favorable agreement with the simulation data without considering the homonuclear dipole-dipole interactions. PMID- 22055981 TI - Midwives at youth clinics attitude to HPV vaccination and their role in cervical cancer prevention. AB - OBJECTIVE: To explore youth clinic midwives role in cervical cancer prevention and their attitude to HPV vaccination. STUDY DESIGN: Individual interviews with 13 midwives working at youth clinics in Sweden. The interviews were recorded, transcribed, and analysed by qualitative content analysis. RESULTS: Three themes were identified in the qualitative content analysis: "Cervical cancer prevention not a prioritised area", "Ambivalence to the HPV vaccine", and "Gender and socioeconomic controversies". Few midwives talked spontaneously about cervical cancer prevention. The responsibility for providing information about HPV vaccination was considered as primarily that of school health nurses and parents. Midwives were positive about the HPV vaccination, but recognised certain risks, such as its potential negative impact on cervical cancer screening and increased sexual risk taking. The midwives expressed concerns with medical risks, such as side effects and unknown long-term effects of the HPV vaccine. The midwives in the study had ethical concerns that boys were not included in the program and not all families had the financial resources to vaccinate their children. Thus, weak socioeconomic groups might be excluded. CONCLUSION: The midwives considered cervical cancer prevention as important, but did not integrate information on the HPV vaccine into their routine work, mainly because young people visiting youth clinics had had their sexual debut and they were concerned about the medical risks and that the vaccine was too expensive. PMID- 22055982 TI - Perceived family perceptions of breastfeeding and Chinese new mothers' breastfeeding behaviors. AB - OBJECTIVE: To provide an understanding of Chinese new mothers' breastfeeding behaviors and especially to explore the relationship between the mothers perceived family perception about breastfeeding and the new mothers' breastfeeding behaviors. STUDY DESIGN: A cross-sectional questionnaire survey was conducted in Beijing and Yinchuan, the capital of Ning Xia Province, China. 214 new mothers with a baby at the age of 4 months were recruited to the study. The family perception of breastfeeding scale and the new mothers' breastfeeding behavior record were used. RESULTS: The response rate was n=200, 94%. Most of the new mothers perceived positive family perceptions about breastfeeding with an average score of 23.13 using the family perception of breastfeeding scale. Nearly half of the respondents reported that they exclusively breastfed their infants (n=94, 47%). The main reason for breastfeeding difficulty was inadequate lactation (n=56, 69%). The new mothers who breastfed their infants mentioned significantly stronger family perceptions/support compared to those who used mixed feeding or artificial feeding (p<0.001). There were no significant differences (p>0.05) in the types of mothers' feeding behaviors across the different age group, occupation, ethnicity, educational level, mode of delivery, the time of the baby's first suck, bottle feeding before the baby's first suck and the time of having colostrums. CONCLUSION: It is suggested to develop some strategies, such as family-centered antenatal and postnatal education programmes, to increase the rate of exclusive breastfeeding by influencing new mothers' families about breastfeeding. Further research is needed to explore socio demographic variables associated with new-mothers' breastfeeding behaviors. PMID- 22055983 TI - Oxytocin augmentation during labor: how to implement medical guidelines into clinical practice. AB - OBJECTIVE: To describe an extensive process to implement guidelines for oxytocin use during labor and to report its effects on compliance to clinical practice guidelines after 1 year. STUDY DESIGN: A multifaceted strategy was developed to involve all obstetric staff and identify possible local barriers to change in advance. The process lasted for more than 1 year. MAIN OUTCOME MEASURES: To describe the implementation of oxytocin use according to the new guidelines, and to compare management in clinical practice with guideline recommendations from audits performed before and after the project. RESULTS: Identification of possible barriers to change, academic detailing, audits with feedback, and local opinion leaders were important factors for a successful process. Documentation of the indication for oxytocin use increased from 54% before, to 86% after the completion of the project (P<0.01). The percentage of incidents in which oxytocin augmentation was started before the diagnosis of labor dystocia was reduced from 40% to 11% (P<0.01). Improvement was found in the documentation of cardiotocography (from 5% to 58%, P<0.01) and contraction frequency at the start of the infusion (from 23% to 63%, P<0.01). CONCLUSIONS: Our multifaceted strategy involved all obstetric staff, lasted for more than a year, and improved management of oxytocin use according to clinical guidelines. Established rules for documentation were used as a check list to monitor oxytocin use. However, audits with feedback need to continue for medical safety, and have been planned to take place every 6 months. PMID- 22055984 TI - Swedish midwives' views on severe fear of childbirth. AB - OBJECTIVE: To describe the views of Swedish midwives on severe fear of childbirth (SFOC). STUDY DESIGN: In this cross sectional study, a random sample of 1000 midwives, selected from the database of the Swedish Association of Midwives, received a questionnaire. The response rate was 84% (n=834), with 726 questionnaires included in the final analysis. MAIN OUTCOME MEASURES: The views of midwives on SFOC in different contexts of work: antenatal care clinic (ACC), labour ward (LW) either ACC/LW or Neither-Nor ACC/LW. RESULTS: The majority of respondents thought that the frequency of SFOC has increased during the last 10 years (67%), and that pregnant women today are more likely to discuss their fears (70%). Midwives at ACCs thought that special education in SFOC is needed (p<0.001) and that they have more responsibility to identify women with SFOC (p<0.001) than midwives at LWs. The majority of respondents, both at ACCs (60%) and LWs (65%), intuitively sensed when they were meeting a woman with SFOC. Opinions among midwives who alternate between working in ACCs and LWs reflected the views of the midwives working either in an ACC or an LW. CONCLUSIONS: The views of midwives on SFOC are partly in concordance and partly contradictory in relation to the different workplaces as well as research data. Knowledge of the views of midwives on SFOC is a necessary pre-requisite to improve care for pregnant women. PMID- 22055985 TI - How to determine symptom severity in premenstrual syndrome: a combination of daily symptom ratings and interviews. AB - OBJECTIVE: To investigate how premenstrual symptoms are experienced and affect daily life, and to see if there is an agreement in reported symptom severity based on interviews compared to ratings on a symptom rating scale. STUDY DESIGN: Twenty-two women with different degree of premenstrual symptoms were interviewed about their symptoms. Based on the luteal-phase interviews, they were categorized in four different severity groups: severe (n=5), moderate (n=3), mild (n=8), and no symptoms/cyclicity (n=6). The interviews were then compared with rated symptom scores, number of expressed symptoms per day, number of days with symptoms, and daily life impairment. MAIN OUTCOME MEASURES: Agreement between rated symptom scores and reported symptoms in the interviews. RESULTS: Comparing seven days in luteal phase scorings with interview data the group with no symptoms/cyclicity showed high agreement between severities reported in the interviews and daily rated scores. Among women who reported severe symptoms, an agreement was seen in three out of five. In the mild/moderate group, the agreement was less conclusive. The day of interview there was a high agreement between data from the reported symptom ratings and symptoms reported in the interview. CONCLUSION: Rated symptom scores the day of interview reflects well symptoms reported in the interviews. Mean symptom scores for seven luteal phase days showed an agreement between symptom ratings and symptoms expressed in interviews among women with severe symptoms and no symptoms/cyclicity. In the group with mild/moderate symptoms, data was less conclusive. PMID- 22055986 TI - Cognizance of sexually transmitted infections among low-income men in western Kenya. AB - Sexually transmitted infections (STIs) pose a worldwide health problem. To improve the efforts of prevention of STIs it is important to gain insight into the awareness of STIs among people in the society. OBJECTIVE: To describe the cognizance of STIs among low-income men in western Kenya. METHOD: Data was collected from eight focus groups consisted of 64 men between 15 and 54 years of age. The interviews were audio taped and content analysis was used for the analysis. FINDINGS: Three categories were derived: Consciousness of STIs, Risk of and prevention of STIs, and Marital relationship and STIs. The results indicate that men had some limited consciousness of STIs but that there were misunderstandings. The treatments the men mentioned were hospital treatment help, from traditional herbalists and self-administration. Condoms were regarded as an effective prevention method, but there were obstacles to using them as well as to talking about STIs within marriage. CONCLUSION: The study stresses the need to promote cognizance of STIs, including gender aspects, and to reduce the gap between knowing and practising. PMID- 22055987 TI - Organizational factors associated with screening for military sexual trauma. AB - PURPOSE: This exploratory study investigated organizational factors associated with receipt of military sexual trauma (MST) screening during an early timeframe of the Veterans Health Administration's (VHA) implementation of the universal MST screening policy. METHODS: The sample consisted of all VHA patients eligible for MST screening in fiscal year 2005 at 119 VHA facilities. Analyses were conducted separately by gender and by user status (i.e., new patients to the VHA health care system in FY 2005 and continuing users who had previously used the VHA health care system in the past year). Multivariate generalized estimating equations were used to assess the effects of facility-level characteristics and adjusted for person-level covariates. RESULTS: Facility-level mandatory universal MST screening policies were associated with increased odds of receiving MST screening among new female patients and both continuing and new male patients: Odds ratio (OR), 2.87 (95% confidence interval [CI], 1.39-5.89) for new female patients; OR, 8.15 (95% CI, 2.93-22.69) for continuing male patients; and OR, 4.48 (95% CI, 1.79-11.20) for new male patients. Facility-level audit and feedback practices was associated with increased odds of receiving MST screening among new patients: OR, 1.91 (95% CI, 1.26-2.91) for females and OR, 1.86 (95% CI, 1.22-2.84) for males. Although the facility-level effect for women's health clinic (WHC) did not emerge as significant, patient-level effects indicated that among these facilities, women who used a WHC had greater odds of being screened for MST compared with women who had not used a WHC: OR, 1.79 (95% CI, 1.18-2.71) for continuing patients and OR, 2.20 (95% CI, 1.59-3.04) for new patients. CONCLUSION: This study showed that facility policies that promote universal MST screening, as well as audit and feedback practices at the facility, significantly improved the odds of patients receiving MST screening. Women veterans' utilization of a WHC was associated with higher odds of receiving MST screening. This study provides empirical support for the use of policies and audit and feedback practices which the VHA has used since the implementation of the MST screening directive to encourage compliance with VHA's MST screening policy and is likely associated with the present-day success in MST screening across all VHA facilities. PMID- 22055988 TI - It's the amount of thought that counts: when ambivalence contributes to mammography screening delay. AB - PURPOSE: This study examines whether ambivalence toward mammography screening, as moderated by total amount of thought given to the reasons for and against getting mammograms at recommended intervals, predicts greater delay in obtaining subsequent screening mammograms. METHODS: A sample of 3,430 insured women with recent (within the last 8-9 months) screening mammograms completed telephone interviews as part of a 5-year intervention study to achieve sustained adherence to annual-interval mammography. Delay was assessed by the number of days between mammograms. RESULTS: Controlling for demographic factors and perceived screening barriers, days between mammograms increased as ambivalence and thought increased. Thought moderated ambivalence: Among women who were most ambivalent, women obtained mammograms 1 month earlier for each unit increase in thought. CONCLUSION: Future studies should test innovative ways to resolve ambivalence and increase thought about consequences of getting mammograms as a strategy to promote mammography screening adherence. PMID- 22055989 TI - The relation between event apprehension and utterance formulation in children: Evidence from linguistic omissions. AB - The relation between event apprehension and utterance formulation was examined in children and adults. English-speaking adults and 4-year-olds viewed motion events while their eye movements were monitored. Half of the participants in each age group described each event (Linguistic task), whereas the other half studied the events for an upcoming memory test (Nonlinguistic task). All participants then completed a memory test in which they identified changes to manners of motion and path endpoints in target events. In the Nonlinguistic task, eye movements and memory responses revealed striking similarities across age groups. Adults and preschoolers attended to manner and path endpoints with similar timing, and in the memory test both successfully detected manner and path changes at similar rates. Substantial differences in production emerged between age groups in the Linguistic task: whereas adults usually mentioned both manners and paths in their event descriptions, preschoolers tended to omit one event component or the other. However, eyegaze patterns remained equivalent across the two age groups, with both children and adults allocating more attention to event components that they planned to talk about. Children in the Linguistic task were at chance in the memory test, whereas adults actually showed a memory benefit as compared to the Nonlinguistic task. We conclude that developmental differences in the description of motion events are not due to pure attentional differences between adults and children, but leave open the possibility that they stem from limitations that are solely linguistic in nature or that arise at the interface of attention and language production. PMID- 22055990 TI - AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update: a guideline from the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and the Preventive Cardiovascular Nurses Association. PMID- 22055991 TI - TP53 gene expression in HPV-positive oral tongue SCC and its correlation with nodal metastasis. AB - In this study, we investigated the prevalence of human papilloma virus (HPV) infection and TP53 expression in patients with squamous cell carcinoma (SCC) of the tongue and, subsequently, its significance in cervical lymph node metastases and tumor differentiation. Sections of formalin-fixed, paraffin-embedded tissue blocks from 94 histologically confirmed tongue SCC cases were investigated in this study. Immunohistochemistry was used to study TP53 expression, and polymerase chain reaction (PCR) was performed for the detection of high risk HPV types (16 and 18). The frequency of HPV-16 and HPV-18 infection was 10.6% and 16%, respectively. Overexpression of TP53 was observed in 70.2% of patients. Young patients (aged below 45 years) comprised 20% of all patients. There was no significant association between TP53, HPV-16, or HPV 18 presence and higher stages of the tumor, tumor differentiation, or presence of nodal metastasis. Although an association between head and neck SCC and HPV infection is being recognized and reported, our data implicate that HPV infection or TP53 expression does not play a significant role in oral tongue SCC pathogenesis, differentiation, or metastasis, as seen in our patients. PMID- 22055992 TI - Beef quality assessed at European research centres. AB - Loin steaks and cubes of M. semimembranosus from eight (12 month old) Galloway steers and eight (16-18 month old) Charolais cross steers raised in England and from which the meat was conditioned for 2 or 10 days, were assessed in research centres in Belgium, Denmark, England, France, the Federal Republic of Germany, Ireland, Italy and the Netherlands. Laboratory panels assessed meat by grilling the steaks and cooking the cubes in casseroles according to local custom using scales developed locally and by scales used frequently at other research centres. The meat was mostly of good quality but with sufficient variation to obtain meaningful comparisons. Tenderness and juiciness were assessed most, and flavour least, consistently. Over the 32 meats, acceptability of steaks and casseroles was in general compounded from tenderness, juiciness and flavour. However, when the meat was tough, it dominated the overall judgement; but when tender, flavour played an important role. Irish and English panels tended to weight more on flavour and Italian panels on tenderness and juiciness. Juciness and tenderness were well correlated among all panels except in Italy and Germany. With flavour, however, Belgian, Irish, German and Dutch panels ranked the meats similarly and formed a group distinct from the others which did not. The panels showed a similar grouping for judgements of acceptability. French and Belgian panels judged the steaks from the older Charolais cross steers to have more flavour and be more juicy than average and tended to prefer them. Casseroles from younger steers were invariably preferred although the French and Belgian panels judged aged meat from older animals equally acceptable. These regional biases were thought to be derived mainly from differences in cooking, but variations in experience and perception of assessors also contributed. PMID- 22055993 TI - The incidence of dark cutting beef in Sweden. AB - The incidence of DFD (Dark, Firm, Dry) in Swedish cattle was studied at four abattoirs and the influence of some parameters of special interest for the development of DFD were evaluated. The pH was measured in a total of 2686 carcasses of different categories. Carcasses with a pH(24) >= 6.2 were classified as being DFD. Only for electrically stimulated carcasses could the pH(24) be considered to be the ultimate pH value. DFD incidences of 3.4% and 13.2% were recorded as overall means for electrically stimulated and non-stimulated carcasses, respectively. The highest incidence was found in young bull carcasses having almost twice as high an incidence of DFD compared with the other categories. Considering seasonal variations, the highest incidence of DFD was found in the period May to August but significant differences in pH were found only for short lairage times. Overnight lairaging increased the incidence of DFD. However, the influence of the lairage time is closely related to the lairage conditions and needs further study. PMID- 22055994 TI - Responses of different types of ox muscle to electrical stimulation. AB - The effects of electrical stimulation on fall in pH upon stimulation (DeltapH), rate of pH fall (dpH/dt at 35 degrees C, cold shortening and muscle ultrastructure were investigated for the Cutaneus trunci (predominantly fast twitch glycolytic fibres), the Masseter and Diaphragm (predominantly slow-twitch oxidative fibres) and the Sternomandibularis and Longissimus dorsi (bot fast- and slow-twitch fibres) of the ox. The Masseter and Diaphragm showed a small DeltapH and no increase in dpH/dt upon stimulation. Stimulation produced supercontracture but no tearing of the fibres throughout all of the Masseter. Stimulation of the Cutaneus trunci resulted in a significantly increased DeltapH and dpH/dt, loss of glycogen, mitochondrial swelling but no gross sarcomere changes. The Longissimus dorsi and Sternomandibularis had a moderate DeltapH and an increase in dpH/dt intermediate between that of the Masseter and the Cutaneus trunci. The Longissimus dorsi showed supercontracture, but the Sternomandibularis did not. Cold shortening responses at 2 degrees C and 0 degrees C were virtually unaffected by stimulation, being greatest in the Masseter and Diaphragm and least in the Cutaneus trunci. All muscles showed significantly greater shortenings at 0 degrees C than 2 degrees C. Stimulation of the Cutaneus trunci did not affect the tenderness of the cooked meat, but the toughness increased dramatically in cold shortened Cutaneus muscle, regardless of stimulation. The Cutaneus trunci least requires stimulation as it does not cold shorten appreciably and therefore early rigor would confer no advantage. The Masseter and Diaphragm have a fast dpH/dt and therefore would enter rigor early. Mixed muscles apparently have the combined, least desirable characteristics of the muscle fibre types-i.e. their rate of rigor development is slow and they cold shorten. Electrical stimulation confers a significant advantage by mitigating these mixed-muscle characteristics in carcass muscles. PMID- 22055995 TI - The time required for recovery from mixing stress in young bulls and the prevention of dark cutting beef. AB - Two trials were conducted in which a total of twenty-eight Friesian bulls (12 months old) were slaughtered 0, 1, 2, 4, 7, 9 or 10 days after they had been mixed with unfamiliar animals overnight. The resulting behavioural interactions and associated physical activity led to large rises in plasma creatine phosphokinase (CPK) activity and free fatty acid (FFA) concentration and a decrease in plasma lactate. In the second trial the relative number of interactions engaged in by each animal was estimated. Bulls which exhibited the most interactions had the highest levels of plasma CPK and FFA after mixing. Liver and muscle glycogen were depleted by mixing. Animals killed on days 0 and 1 after mixing had low concentrations of liver glycogen compared with animals allowed longer to recover. Concentrations of glycogen in the M. longissimus dorsi (LD) had recovered by day 4 and in the M. psoas by day 2. Muscle glycogen concentrations were reflected in the ultimate pH (pHu) of the meat. All animals killed immediately after mixing produced carcasses with pHu>6. in the LD. By the second day of recovery muscle glycogen stores had been repleted sufficiently so that all animals had muscles with pHu<6. However, the LD from these animals was still very slightly darker than those killed after 7 or more days of recovery although this was probably not commercially significant. It was concluded that, if young bulls from separate rearing groups are mixed before slaughter, either on the farm or during lairage, then they require resting with food for at least 48 h before being killed to ensure that no carcasses are produced with high pHu in the musculature. PMID- 22055996 TI - Comparative study of buffalo meat and beef. AB - The aim of the experiment described in this paper was to compare buffalo and cattle breeds for meat production. Bulls and steers of both species were compared. Buffaloes and cattle were of comparable conformation on a weight to length ratio basis when slaughtered at the same liveweight. Apart from sex and weight effects, species did affect the conformation and growth of live animals, the largest differences between species being evident in the younger animals. As regards slaughter characteristics, although differences in carcass yield were slight between species, systematic differences appeared, with a higher head and skin weight for buffaloes. A higher proportion of fat was noted in the 11th rib joint of buffaloes than of cattle at the lighter weights but the difference between species lessened with slaughter weight. As far as meat quality is concerned, two major effects of species on muscle pH (24 h post slaughter) and the shear strength of raw muscle were noted. Buffaloes, which had a lower muscle pH than cattle, displayed a significantly smaller amount of collagen in the muscles studied, but the species did not differ significantly in the degree of intramuscular collagen crosslinking. PMID- 22055997 TI - Developments in food proteins-2 Edited by B. J. Hudson, Applied Science Publishers, London and New York, 1983. Price: L36.00. PMID- 22055998 TI - Feature extraction for ECG heartbeats using higher order statistics of WPD coefficients. AB - This paper describes feature extraction methods using higher order statistics (HOS) of wavelet packet decomposition (WPD) coefficients for the purpose of automatic heartbeat recognition. The method consists of three stages. First, the wavelet package coefficients (WPC) are calculated for each different type of ECG beat. Then, higher order statistics of WPC are derived. Finally, the obtained feature set is used as input to a classifier, which is based on k-NN algorithm. The MIT-BIH arrhythmia database is used to obtain the ECG records used in this study. All heartbeats in the arrhythmia database are grouped into five main heartbeat classes. The classification accuracy of the proposed system is measured by average sensitivity of 90%, average selectivity of 92% and average specificity of 98%. The results show that HOS of WPC as features are highly discriminative for the classification of different arrhythmic ECG beats. PMID- 22055999 TI - Morphological-metabolic evaluation of the urachal mucinous adenocarcinoma by positron emission tomography-computed tomography (PET-CT). AB - The urachal mucinous adenocarcinoma is a rare malignant neoplasm located between the bladder and the umbilicus. It is usually found in an advanced stage at the moment of diagnosis. We have analyzed a clinical case in which the PET-CT study provided valuable morphological and metabolic information for diagnosis and staging. PMID- 22056001 TI - A diffuse branching pattern of biliary FDG activity: infective or neoplastic? PMID- 22056002 TI - Incidental finding of hiatal hernia on (99m)Tc-sestamibi whole-body scan in thyroid cancer evaluation. PMID- 22056004 TI - Amyloid PET imaging with 11C-PIB in two patients with cognitive impairment. PMID- 22056005 TI - An upper limb variant of RLS? Report of 2 cases. PMID- 22056007 TI - Anabolic agents and meat quality: A review. AB - This review considers the results of more than sixty studies on the possible effects of anabolic agents on the meat quality parameters of the three main red meat species and poultry. The information is grouped into three main sections: carcass composition, muscle quality and eating quality. Each section is further divided by animal species, with consideration given to differences due to sex or age. Anabolic agents appear to have some effect on the carcass composition of animals; depending upon the type used, they can cause an increase in the ratio of muscle to fat in female and castrate animals, or a decrease in this ratio in entire males. Such differences are usually reflected in related changes in the chemical composition of the meat. Few consistent effects, however, have been reported in the eating quality of the cooked meat in terms of texture, flavour, juiciness or cooking loss, indicating that the basic eating quality attributes important to the consumer are largely unaffected by hormone treatment. PMID- 22056006 TI - A model to predict mortality following Pseudomonas aeruginosa bacteremia. AB - Infections caused by Pseudomonas aeruginosa are associated with significant mortality. Existing mathematical models identifying mortality risk factors lack validation. We developed and validated a model to predict mortality in patients with P. aeruginosa bacteremia. Risk factors for 30-day mortality were examined through multivariate logistic regression in 114 patients. Independent predictors of mortality included isolation of a multidrug-resistant strain, APACHE II >= 23, and age >= 65 years. Clonality was assessed for multidrug-resistant isolates. Predicted probability of 30-day mortality was validated in 49 patients, after conditioning the model by the identified risk factors. The patients were split into 'high-risk' and 'low-risk' groups based on model-predicted mortality; the observed/expected ratios were 1.21 and 1.92, respectively. Our model was reasonable in predicting 30-day mortality in patients with P. aeruginosa bacteremia. Our results may be useful for developing strategies to reduce mortality attributed to P. aeruginosa. PMID- 22056008 TI - Post-mortem degradation of gap filaments at different post-mortem pHs and temperatures. AB - Super-stretched muscle fiber bundles (<10 min post mortem) were incubated at one of four combinations of temperature and pH (pH 5.5, 37 degrees C; pH 5.5, 0-4 degrees C; pH 7.4, 37 degrees C; pH 7.4, 0-4 degrees C) for 1 h prior to fixation and embedding for transmission electron microscopy. These tissues were compared with controls fixed immediately after stretching. Disruption of gap filament ultrastructure was greatest in those muscle bundles incubated at pH 5.5 and 37 degrees C. It was determined that pH had a greater influence upon gap filaments than did temperature and that pH 5.5 caused more gap filament disruption than pH 7.4. Other structural alterations of the stretched muscle included more glycogen granule disruption at pH 7.4 and pulling of groups of thick filaments toward the Z-lines within a sarcomere. A pulling of alternate thick filaments toward opposite Z-lines was not observed. It was concluded that gap filament disruption may occur very rapidly in post-mortem muscle. PMID- 22056009 TI - Collagen-bound collagenolytic enzyme in rabbit skeletal muscle. AB - In order to elucidate the changes in connective tissue which occur during meat conditioning, a study was made of the collagenolytic enzyme in muscle. Collagenolytic enzyme was detected in the collagen fraction of rabbit skeletal muscle. Electrophoretic and electron microscopic studies of the effects of the collagenolytic enzyme on the collagen indicated that this enzyme could digest the beta-subunit of the soluble collagen and cause fragmentation, swelling and splitting of the collagen fibrils. PMID- 22056010 TI - Natural gas operations: considerations on process transients, design, and control. AB - This manuscript highlights tangible benefits deriving from the dynamic simulation and control of operational transients of natural gas processing plants. Relevant improvements in safety, controllability, operability, and flexibility are obtained not only within the traditional applications, i.e. plant start-up and shutdown, but also in certain fields apparently time-independent such as the feasibility studies of gas processing plant layout and the process design of processes. Specifically, this paper enhances the myopic steady-state approach and its main shortcomings with respect to the more detailed studies that take into consideration the non-steady state behaviors. A portion of a gas processing facility is considered as case study. Process transients, design, and control solutions apparently more appealing from a steady-state approach are compared to the corresponding dynamic simulation solutions. PMID- 22056011 TI - Similar rates of chromosomal aberrant secondary oocytes in two indigenous cattle (Bos taurus) breeds as determined by dual-color FISH. AB - In vitro-matured metaphase II (MII) oocytes with corresponding first polar bodies (I pb) from two indigenous cattle (Bos taurus) breeds have been investigated to provide specific data upon the incidence of aneuploidy. A total of 165 and 140 in vitro-matured MII oocytes of the Podolian (PO) and Maremmana (MA) breeds, respectively, were analyzed by fluorescence in situ hybridization using Xcen and five chromosome-specific painting probes. Oocytes with unreduced chromosome number were 13.3% and 6.4% in the two breeds, respectively, averaging 10.2%. In the PO, out of 100 MII oocytes + I pb analyzed, two oocytes were nullisomic for chromosome 5 (2.0%) and one disomic for the same chromosome (1.0%). In the MA, out of 100 MII oocytes + I pb, one oocyte was found nullisomic for chromosome 5 (1.0%) and one was disomic for the X chromosome (1.0%). Out of 200 MII oocytes + I pb, the mean rate of aneuploidy (nullisomy + disomy) for the two chromosomes scored was 2.5%, of which 1.5% was due to nullisomy and 1.0% due to disomy. By averaging these data with those previously reported on dairy cattle, the overall incidence of aneuploidy in cattle, as a species, was 2.25%, of which 1.25% was due to nullisomy and 1.0% due to disomy. The results so far achieved indicate similar rates of aneuploidy among the four cattle breeds investigated. Interspecific comparison between cattle (Xcen-5 probes) and pig (Sus scrofa domestica) (1-10 probes) also reveal similar rates. Further studies are needed that use more probes to investigate the interchromosomal effect. Establishing a baseline level of aneuploidy for each species/breed could also be useful for improving the in vitro production of embryos destined to the embryo transfer industry as well as for monitoring future trends of the reproductive health of domestic animals in relation to management errors and/or environmental hazards. PMID- 22056012 TI - Effects of polymorphonuclear neutrophile infiltration into the endometrial environment on embryonic development in superovulated cows. AB - Recent studies on bovine uterine disorders have demonstrated that endometrial infiltration with polymorphonuclear neutrophils (PMN) in the postpartum period or at the time of breeding negatively affects reproductive performance. The objective of the present study was therefore to analyze the effect of endometrial PMN infiltration on superovulation outcome. Cows were synchronized and superovulated receiving a total of three artificial inseminations within 24 h. Endometrial cytologic samples were collected by cytobrush technique at first artificial inseminations (AI) (d -1) and before embryo flush (d 7). Embryos were recovered by uterus flushing at Day 7 and evaluated for total cell number and apoptotic cell index. A total of 425 embryos were flushed out of 48 superovulated cows. The PMN dynamics from first AI to flushing had a significant effect on flushing outcome. Significant differences in terms of number of palpable corpora lutea (14.1 vs 7.2) and transferable embryos (8.8 vs 1.9) were found between cows with PMN proportions increasing from zero (0%) at AI to positive proportions (> 0%) at flushing (group PMNZP) and cows with higher endometrial PMN proportions decreasing to lower but still positive proportions from AI to flushing (group PMNHL). Moreover, cows classified to PMN class zero at first AI flushed a significant higher number of total embryos (10.3 vs 6.9) and transferable embryos (6.8 vs 3.7) compared to cows of PMN class positive at first AI (P > 0.05) in our study. Considering a significant interaction effect between PMN class at first AI and flush (P < 0.05), PMN class at first AI (d -1) correlated significantly with number of total flushed and transferable embryos only in combination with a positive PMN class at flush (d 7). Likewise, PMN class at flush (d 7) beard a significant effect on total number of flushed embryos only when classified to PMN class zero at first AI. Collectively, the present work is the first study that demonstrated a significant relationship between endometrial PMN infiltration at first AI as well as PMN dynamic from first AI to time of flush and superovulation outcome. PMID- 22056013 TI - Expression of vascular endothelial growth factor (VEGF) transcript and protein in the testis of several vertebrates, including endangered species. AB - Vascular endothelial growth factor (VEGF) is known to influence the testis function. To establish the role of VEGF in the testis of a variety of species, we analyzed the expression of VEGF transcript using human gene-specific primers by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis in the testes of 18 vertebrates, including a few endangered species. An amplicon of 566 bp representing VEGF(165) was identified in testis of all species in this study. Sequence analysis of these amplicons revealed 84 to 96% homology to available human VEGF sequence and to the VEGF sequences of other species in GenBank. Immunohistochemical analysis revealed expression of VEGF protein, primarily in Sertoli and Leydig cells and occasionally in the germ cells of the testis sections. It can be concluded from this study that expression of VEGF transcript is conserved in the testis of several vertebrates and may have a role in the process of spermatogenesis. PMID- 22056014 TI - Nucleolar organizer regions (NORs) distribution and behavior in spermatozoa and meiotic cells of the horse (Equus caballus). AB - Nucleolar organizing regions (NORs) containing rDNA gene clusters have been assigned to the equine autosomes ECA1, ECA28, and ECA31. Active NORs (Ag-NORs) are associated with argyrophilic proteins, which allow them to be readily identified using silver staining techniques. Fluorescence in situ hybridization (FISH) for rDNA can also be used to visualize all NOR clusters in the nucleus, regardless of whether they are active or inactive. The present study analyzed the distribution and behavior of equine Ag-NOR and NOR clusters in horse spermatozoa and during male meiosis by FISH and silver staining. The NOR foci were observed to be variable in number, size, and shape, but were usually located centrally and appeared as one or two nucleolus-like structures in the spermatozoa head. Three distinctive FISH signals identified the NOR-bearing chromosome pairs during the synaptic cell stage of meiosis I. At diakinesis/metaphase I, as well as different stages of meiosis II, FISH signals clearly depicted the NOR-bearing sister chromatids. The synaptonemal complexes of primary spermatocytes consistently showed three rDNA foci following FISH, but variably demonstrated two or three Ag NOR bodies following silver staining. We propose rDNA loss and gain during unequal crossing-over events could be both a direct and indirect cause of variation in equine NOR foci. Additionally, our cytogenetic analysis did not confirm the presence of a fourth pair of NORs-bearing chromosomes in the horse, which is contrary to previously mitotic published data. PMID- 22056015 TI - Differential expression of cyclic-AMP responsive element modulator (CREM) mRNA isoforms during testicular development of boars. AB - The cyclic-AMP responsive element modulator (CREM) transcription factor, a key regulator of spermatogenesis, can activate or repress gene expression by differential expression of alternatively spliced mRNA isoforms. The objective of this study was to report the sequences of the predominant CREM mRNA isoforms with leader exons B, theta1, theta2, in addition to the relative expression of these transcripts, in immature and adult boar testes. Activator CREM isoforms taugamma (containing the B exon), theta1taugamma and theta2taugamma, were expressed in the adult boar testes, but not in immature testes. The CREM theta2taugamma isoform had the highest expression levels in the adult boar testes compared to the taugamma and theta1taugamma isoforms (theta2taugamma = 4.94 +/- 1.49 in contrast to taugamma = 1.66 +/- 0.79 and theta1taugamma = 2.32 +/- 0.72; mean +/- SD; P < 0.01). Interestingly, the predominant CREM mRNA isoforms in adult boar testes contained the C and gamma exons; these exons are not present in human and rodent CREM mRNA, demonstrating species-specific expression. In contrast to the adult CREM isoforms, only CREM mRNA isoforms with the B exon (tau1 and alpha) were amplified in the 21 d (immature) boar testes. Further understanding of CREM mRNA isoform expression and regulation during boar spermatogenesis could contribute to our knowledge of spermatogenic efficiency in this species. PMID- 22056016 TI - Embryo quality and transcervical technique are not the limiting factors in donkey embryo transfer outcome. AB - Embryo transfer (ET) in the donkey resulted in a very low recipient pregnancy rates. The aim of these studies was to investigate if nonsurgical transfer techniques or donkey embryo quality affect donkey recipient pregnancy failure. In Study 1, the impact of transfer technique was investigated by evaluating if cervical catheterization is associated with prostaglandin release and suppression of luteal function and if donkey recipients would become pregnant after nonsurgical transfer of horse embryos. Four jennies, from 5 to 8 d after ovulation, were submitted to a sham transcervical ET and to evaluation of PGFM and progesterone plasma concentrations. Five 8 d horse embryos were nonsurgically transferred into synchronized donkey recipients (HD). Cervical stimulation caused a transient PGF(2alpha) release in two of four jennies in the absence of a significant decrease in progesterone plasma concentration. All transferred horse embryos resulted in pregnancies in the jenny recipients. In Study 2, donkey embryo viability was investigated by 1.2 meters, 6-diamidino-2-phenylindole (DAPI) staining of 10 embryos and by the transfer of 6 and 12 donkey embryos in synchronized mare (DH) and donkey (DD) recipients, respectively, of known fertility. The estimated proportion of dead cells in DAPI stained embryos was 0.9% (range 0-3.9%) and below what is considered normal (20%) for horse embryos. Three of six and six of 12 of the DH and DD ETs, respectively resulted in pregnancies at 14 and 25 d (50%), a higher pregnancy rate than previously reported after DD ET. The overall results of this study suggest that the transcervical technique for ET and donkey embryo viability are not the reasons for the low pregnancy rates that have previously been described in donkey recipients, and that nonsurgical ET in donkeys can result in acceptable results. PMID- 22056017 TI - Comparison of assessment of pigeon sperm viability by contrast-phase microscope (eosin-nigrosin staining) and flow cytometry (SYBR-14/propidium iodide (PI) staining) [evaluation of pigeon sperm viability]. AB - The aim of these experiments was to compare the conventional, microscopic method of evaluating pigeon sperm viability to sperm assessed by flow cytometry. Semen was collected twice a week from two groups of pigeons. In every group were 20 males (Group I: meat-type breed; Group II: fancy pigeon breed). Semen was collected using the lumbosacral and cloacal region massage method. Ejaculates collected from each group were pooled and diluted to 10 * 10(6) sperm/ml in BPSE solution. Samples were divided into three equal parts and estimated after collection as well as after in vitro storage for 3, 6 and 24 h. The first part was using for semen motility evaluation. The proportion of motile spermatozoa (MOT) and progressive movement (PMOT) of fresh and stored semen were evaluated using the CASA-system. The second part was examined subjectively by microscope (eosin-nigrosin (EN), eosin-nigrosin staining), the third one was assessed using dual fluorescence SYBR-14/propidium iodide (PI) and flow cytometry (FC). There were not any significant differences in sperm viability and motility between the groups at 0, 3, 6, and 24 h post collection. The percentage of viable spermatozoa in fresh semen determined by EN and FC was not different in Groups I and II (I - 88.71 +/- 5.42 and 84.01 +/- 3.19, respectively; II-90.87 +/- 6.01 and 87.38 +/- 5.57, respectively). Significantly lower percentages of viable spermatozoa were detected by FC compared to the EN method in both groups after 6 h (P <= 0.05) as well as 24 h (P <= 0.01) of storage. Moreover, the dual fluorescent SYBR-14/PI staining allowed for the identification a third population of double stained, moribund spermatozoa. High positive correlations in percentage of live spermatozoa were noted between EN and FC methods in both groups of birds. Evaluation of sperm viability by FC is a rapid, accurate, sensitive, and objective method for the assessment of pigeon sperm viability in fresh as well as stored semen. PMID- 22056018 TI - Reference values for the genitalia of male dromedary before and after puberty using caliper and ultrasonography in subtropics. AB - The aim of the present study was to characterize the dynamic changes of the testes and the pelvic genitalia in vivo in male dromedary. Eighty-one clinically healthy male dromedaries aged 1.5 to 12 years were assigned for the present study. Testicular length, breadth, and depth as well as epididymal head and tail were measured using caliper and ultrasonography. The pelvic genitalia, including bulbourethral gland, prostate, and pelvic urethra were examined using ultrasonography. The results revealed that the three dimensions of the testes and epididymal tail and head showed significant increase with age (P < 0.01). Concerning the epididymal measurements, differences between the pre- and peri pubertal groups were not significant. Left testes tended to be larger than the right (not statistically significant) although only the breadth of the left testes in the prepubertal group was significantly larger (P < 0.05). The volume of both testes correlated positively with the age (r(2) = 0.91 for left and 1.00 for the right, P < 0.01). There were no significant correlations between the values measured using caliper and those by ultrasonography between groups, but the correlation was highly significant (P < 0.01) for the total number of the examined animals. There were significant and steady increases of the size of bulbourethral gland in all examined groups (P < 0.01). Pars disseminata of the prostate gland and pelvic urethra were significantly higher in sexually mature compared with prepubertal groups (P < 0.01). It was concluded that ultrasonography is a useful tool in studying the developmental changes of the testes and accessory glands of the male dromedary. The obtained data could provide a reference values for predicting camel puberty and future fertility. PMID- 22056019 TI - Influence of testicular hormones on the somatostatin-GH system during the growth promoted transition to puberty in sheep. AB - The aim of the present study was to investigate whether the growth promoted transition to puberty in lambs involved changes in the effects of testicular hormones on somatostatin in hypothalamic neurons and GH secretion. The study was performed in infants (9-week-old) testis-intact (TEI) and orchidectomized (ORCHX) at the sixth week of age, and pubertal lambs (16-week-old) TEI and ORCHX at the 12th week of age (n = 20). In TEI lambs, the changes included a pubertal increase in immunoreactive somatostatin in the periventricular nucleus and median eminence with simultaneous neuropeptide depletion in the median eminence, and a decrease in the percentage of the hypophyseal area (PA) occupied by GH-immunoreactive cells (P < 0.05). The mean concentration of GH in the peripheral blood plasma was greater (P < 0.001) in early infancy (5 wk), because of the greater (P < 0.0001) pulse amplitude, and then uniformly low until puberty. The postnatal increase in the body weight (BW) was prominent (P < 0.01) in middle-late infancy (9-12 wk) because of the large daily live-weight gain. After orchidectomy somatostatin was abundant. This effect on nerve terminals in the median eminence was greater (P < 0.01) in infancy and lesser (P < 0.05) in puberty. Conversely, the PA occupied by GH cells was lower in the ORCHX pubertal lambs compared to TEI lambs (P < 0.05). The GH concentration and pulse characteristics were less (P < 0.05) in the infantile and pubertal ORCHX lambs compared to the TEI lambs. However, this effect was weak (P < 0.05) until middle infancy because of no influence on the GH basal concentration, and strong (P < 0.001) after late infancy. The BW did not differ (P > 0.05) between TEI and ORCHX lambs. Findings suggest activation of GH negative autofeedback loop in middle infancy. Testicular factors may play an inhibitory role in regulating somatostatin accumulation and a stimulatory role in GH secretion until puberty. The start of puberty is related to an attenuation in the stimulatory role of gonadal factors in regulating somatostatin depletion in nerve terminals associated with an intensification of the stimulatory role of gonadal factors in regulating GH secretion. From a somatic perspective of growth rate, these mechanisms do not seem to be important. Thus, testicular factors modulate mechanisms within the somatostatin-GH system to integrate somatotropic and gonadotropic functions at the time of growth-promoted sexual maturation in sheep. PMID- 22056020 TI - EGFR expression and the flexibility of FLEX. PMID- 22056021 TI - EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. AB - BACKGROUND: Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0.871, 95% CI 0.762-0.996; p=0.044) in patients with advanced non small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients. METHODS: We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0-300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (>=200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. FINDINGS: Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99.6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12.0 months [95% CI 10.2-15.2] vs 9.6 months [7.6-10.6]; HR 0.73, 0.58-0.93; p=0.011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9.8 months [8.9-12.2] vs 10.3 months [9.2-11.5]; HR 0.99, 0.84-1.16; p=0.88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0.044). INTERPRETATION: High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting. FUNDING: Merck KGaA. PMID- 22056022 TI - Investigation of cytochrome P450 1A2 and 3A inhibitory properties of Danshen tincture. AB - Danshen (Salvia miltiorrhiza Bunge) as a famous Traditional Chinese medicine is widely used in the treatment of cardiovascular and cerebrovascular diseases in the world. Danshen tincture (DT), extracted from Danshen root with a mixture of water and alcohol, is a commonly used preparation method for human consumption. The aim of this study was to investigate the effects of DT on the cytochrome P450 (CYP) 1A2 and 3A activities by human and rat liver microsomes. Effects of DT were assessed with use of Danshen ethanolic extract (DEE) and selective substrates, markers of CYP activities. DEE (0.5-10 MUg/ml) competitively inhibited human and rat liver microsomal CYP1A2 activity with inhibition constant (K(i)) values at 3.40 and 5.16 MUg/ml, respectively. At the same time, DEE (2.5-20 MUg/ml) not only noncompetitively inhibited human liver microsomal CYP3A4/5 activity with a K(i) of 11.9 MUg/ml, but also competitively inhibited rat liver microsomal CYP3A1/2 activity with a K(i) of 52.1 MUg/ml. The data indicate that DEE inhibited the metabolism of CYP1A2 and 3A substrates in human and rat liver in vitro with different mode of inhibition. This study may be helpful for clinical application of Danshen tincture. PMID- 22056023 TI - Mass spectrometric measurements of the apolipoproteins of bovine (Bos taurus) HDL. AB - As is the case in most mammals, high density lipoproteins (HDL) also comprise the major group of lipid carriers that circulate in bovine (Bos taurus) blood. As a continuation of our proteogenomic studies of mammalian apolipoproteins, we have obtained molecular masses for several of the apolipoproteins associated with bovine HDL. The major apolipoprotein on the HDL surface is apoA-I, but other apolipoproteins were also detected. Using electrospray-ionization mass spectrometry (ESI-MS), we report on values for apolipoproteins, A-I, proA-I and A II, as well as post-translationally modified apoA-I. Analyses of tryptic fragments did reveal the presence of apoA-IV and apoC-III. However, in contrast to our previous studies of other mammalian HDL, we did not detect apoC-I. Interestingly, examination of the current assembly for the bovine genome does not show any evidence for an apoC-I gene. PMID- 22056024 TI - Chemokine mediated neuron-glia communication and aberrant signalling in neuropathic pain states. AB - Treatment of neuropathic pain is problematic; response to current pharmacological interventions is often poor and associated with undesirable side-effects, thus the identification of new targets for treating this condition is needed. Here we collect evidence demonstrating the potential of chemokines as mediators of neuron glia communication and contributors to pain signalling. The expression of chemokines such as CX3CL1, CCL2 and CCL21 and their receptors CX3CR1, CCR2 and CXCR3 is altered in the spinal cord under neuropathic pain conditions and chemokine receptor antagonists attenuate neuropathic pain behaviour. By understanding the mechanisms of chemokine-mediated communication we may expose glial targets as a novel approach for the treatment of neuropathic pain. PMID- 22056025 TI - Noxious mechanosensation - molecules and circuits. AB - Drugs that block mechanically-evoked pain would be useful for many common pain conditions, but appropriate drug development targets have yet to be defined. There is increasing evidence that both peripheral sensory neuron wiring patterns as well as the expression of transducing molecules are important for modality specific pain sensations. Progress in identifying the cell types, candidate transducing molecules and wiring patterns involved in mechanosensation has been dramatic over the past few years. Here we focus on potential mechano-transducing channels, and the relevant cell types and wiring patterns that provide clues for new analgesic drug development strategies. PMID- 22056026 TI - Targeting epigenetic mechanisms for pain relief. AB - Epigenetic changes are chemical modifications to chromatin that modulate gene activity without altering the DNA sequence. While research on epigenetics has grown exponentially over the past few years, very few studies have investigated epigenetic mechanisms in relation to pain states. However, epigenetic mechanisms are crucial to memory formation that requires similar synaptic plasticity to pain processing, indicating that they may play a key role in the control of pain states. This article reviews the early evidence suggesting that epigenetic mechanisms are engaged after injury and in chronic pain states, and that drugs used clinically to target the epigenetic machinery for the treatment of cancer might be useful for the management of chronic pain. PMID- 22056027 TI - Determination of ash content in meat products. AB - Various procedures for determining 'ash' content of meat products have been compared. The ISO method gave significantly higher results than the other methods tested. The standard method (IAS 2-043) gave lower recoveries and, in one of the experiments, lower results for ash content, than the other methods tested. The AOAC and Lees' methods gave high recoveries, but their results for ash content were significantly lower than those of the ISO method. All four methods showed good precision and repeatability. The differences between them although small were statistically significant. The ISO method is recommended on account of its speed, accuracy and reliability. PMID- 22056028 TI - The separation of meat from bone-A review of the mechanics and the problems. AB - With continually increasing demands on the world's food supply, new techniques, improvements to old methods, the recovery and utilisation of waste and the introduction of novel foods are all becoming increasingly important. The separation of residual meat from bone by manual methods is inefficient, time consuming and expensive; mechanical separation is not new, but it is only in recent years that manufacturers have become aware of its potential. There are two main approaches to meat recovery, removal of bone from meat and retrieval of meat from bones. Although the implications of the former are significant, the available methods are largely modifications of manual procedures and limited in application; recovery of meat from bones is, however, in extensive commercial use. This review discusses the methods and mechanics of the latter and the associated problems of handling, storage and recovery, together with the uses of the product, legal requirements and restrictions in the use of mechanically recovered meat (MRM). PMID- 22056029 TI - Effect of post-mortem storage temperatures on isometric tension, pH, ATP, glycogen and glucose-6-phosphate for selected bovine muscles. AB - Relationships between isometric tension development and pH, ATP, glucose-6 phosphate and glycogen levels as a function of post-mortem storage temperature were examined for three bovine muscles. Tension responses in the range of 5-37 degrees C were similar for B. femoris, Vastus lateralis and outer M. semitendinosis. At 0 degrees C, the three muscles developed considerably higher tension than at 5 degrees C. Cold shortening developed only in the outer M. semitendinosis strips at 0 degrees C. At low temperatures the drop in pH lagged compared to the decline in ATP and glycogen and maximum tension was attained several hours after ultimate pH and minimum levels of ATP and glycogen were reached. Glucose-6-phosphate was found to accumulate rapidly at 0 degrees C in both outer M. semitendinosis and B. femoris, being more pronounced in the latter muscle. The responses of glucose-6-phosphate levels suggest that the relative activities of glycolytic enzymes in muscle stored at 0 degrees C are altered compared to those in muscle stored at higher temperatures. PMID- 22056030 TI - The effect of carbon monoxide on bacterial growth. AB - Growth rate studies were conducted with Pseudomonas aeruginosa, Pseudomonas fluorescens, Escherichia coli and Achromabacter under atmospheres containing up to thirty per cent (v/v) carbon monoxide. It was found that atmospheres containing carbon monoxide have a selective action on the type of organism that grows in a mixed culture. Studies with pure cultures demonstrated that carbon monoxide has no effect on the growth of P. aeruginosa, inhibits the growth rate of E. coli by amounts proportional to the concentration of carbon monoxide, increases the lag phase period of growth in Achromobacter and inhibits the growth rate and increases the lag phase period in P. fluorescens. PMID- 22056031 TI - The microbiology of DFD fresh meats: A review. AB - Muscle which is deficient in glycogen because of exercise or stress prior to slaughter produces dark, firm, dry (DFD) meat. Such meat is characterized by a high ultimate pH (>6.0) and deficiencies in glucose and glycolytic intermediates. These factors can result in bacterial spoilage becoming evident at an early stage of growth of the meat flora. Spoilage becomes apparent when bacteria attack amino acids. This does not occur under aerobic conditions until bacteria exhaust the glucose at the meat surface. However, since glucose is absent in DFD meat, amino acids are utilised without delay and spoilage becomes evident at lower cell densities than in normal meat. The absence of glucose also allows the anaerobic flora to produce spoilage odours at an early stage. Additionally, the high pH of DFD meat allows growth of potent spoilage organisms which are inhibited at the usual ultimate pH of meat. Early aerobic spoilage can be prevented by the addition of glucose, but prevention of early anaerobic spoilage requires the addition of a citrate buffer which reduces the surface pH, as well as providing a carbohydrate substrate which is utilised in preference to amino acids. Comparisons can be made between spoilage of DFD red meat and spoilage of white meats from poultry and fish, which normally have a high ultimate pH. PMID- 22056032 TI - Effect of muscle lysosomal enzymes and calcium activated neutral proteinase on myofibrillar ATPase activity: Relationship with ageing changes. AB - Myofibrillar ATPase activities have been used to study the in vitro effect of Ca ANP (Calcium Activated Neutral Proteinase) and lysosomal proteolytic enzymes on the myofibrils at their respective optimal conditions activity. It appeared that the effect of Post-mortem ageing of meat on the Mg?Ca and Mg-EGTA modified ATPase activities can be reproduced by incubating myofibrils with these hydrolytic systems. However, the effect of ageing on the Ca(++)-enhanced ATPase activity of myofibrils was not explained. It was concluded that Ca-ANP and at least one lysosomal thiol protease could be involved in the ageing process. PMID- 22056033 TI - Abnormal granulation of blood granulocytes in mucopolysaccharidosis VI-a case report. AB - Mucopolysaccharidosis (MPS) is a group of lysosomal storage disorders in which there is deficiency of specific enzymes. Depending upon the enzyme which is deficient and the nature of the material that accumulates at various tissues, the MPS is divided into 8 types (MPS I to MPS VIII). In MPS VI, deficiency of aryl B sulfatase leads to the accumulation of dermatan sulfate. Mucopolysaccharidosis VI, also called as Maroteaux-Lamy syndrome, in its severe form presents with bony lesions, corneal clouding, hepatosplenomegaly, cardiovascular abnormalities, and central nervous system deterioration. This form of MPS features the most striking abnormal granulation in the circulating white blood cells. Mucopolysaccharidosis VI has an estimated global incidence of 1 in 340,000. The number of cases showing abnormal granules in the cytoplasm of leucocytes is still rarer. We report a case of MPS VI with abnormal granules in the circulating blood leukocytes. PMID- 22056034 TI - Lipomatosis coli, a mimicker of familial polyposis. AB - Multiple intestinal lipomas (lipomatous polyposis) are quite rare, and they can be quite challenging to diagnose because this condition may be clinically confused with familial adenomatous polyposis with a suggestive family history. Herein, we present a case of lipomatous polyposis that was presented with abdominal pain and, in colonoscopy, had more than 100 polyps. The patient was admitted for surgery with diagnosis of familial polyposis. Resected colon specimen had multiple polyps ranging from 0.1 to 1.5 cm. Microscopically, the polyps were composed of mature adipose tissue with normal overlying mucosa. There were also increased fat cells in the submucosa of the colon adjacent to the polyps. Lipomatous polyposis rarely occurs and can be confused with familial polyposis. Polypectomy is a simple and cost-effective procedure to help in diagnosis and prevent a major surgery. PMID- 22056035 TI - Sclerosing epithelioid fibrosarcoma of the pancreas. AB - Sclerosing epithelioid fibrosarcoma (SEF) is a distinctive variant of fibrosarcoma characterized by epithelioid tumor cells arranged in nests, cords, or sheets embedded within a sclerotic collagenous matrix. It is a relatively newly described malignant fibroblastic tumor, with only fewer than 100 cases reported in English literature. Most cases are located in the lower extremities and limb girdles. Here, we present a case of SEF of the pancreas in a 67-year-old white man and provide a review of literature to date, with emphasis on the differential diagnosis. To our knowledge, this is the first reported case of SEF involving the pancreas. PMID- 22056036 TI - alpha-Fetoprotein-producing ovarian tumor in a postmenopausal woman with germ cell differentiation. AB - alpha-Fetoprotein (AFP)-producing ovarian tumors (APOTs) are rarely encountered in postmenopausal women, irrespective of whether they are of the germ cell or non germ cell type. The APOTs that do occur in postmenopausal women are characterized by variable histologies such as hepatoid carcinoma, yolk sac tumor, and epithelial malignancies, most of which are combined. We herein present a case with APOT, which arose in a 58-year-old, gravida 2, para 2, postmenopausal woman. Preoperatively, the tumor, which was in the right ovary, was found to produce AFP (102768.0 ng/mL). The tumor was evenly composed of glands mimicking secretory endometrial gland or fetal gut accompanied by abundant stroma. Immunohistochemically, these glands were positive for SALL4, glypican-3, and hepatocyte nuclear factor 1beta. We considered the present case as an AFP producing adenocarcinoma with adenofibroma showing germ cell differentiation, but it seemed controversial that this tumor should be designated as a yolk sac tumor of the glandular type. The expression profiles of SALL4, OCT4, glypican-3, and hepatocyte nuclear factor 1beta were thought to provide interesting implications to characterize the present case. PMID- 22056037 TI - Application of the British National Health Service Breast Cancer Screening Programme classification in 226 breast core needle biopsies: correlation with resected specimens. AB - A retrospective study correlating the diagnosis made on core needle breast biopsy (CNB) with the diagnosis made on the final surgical specimen was done using the British National Health Service Breast Cancer Screening Programme (NHSBSP) classification for CNB on 226 patients during a period of 15 months. Statistical analysis was used to evaluate sensitivity, specificity, and positive and negative predictive values of the NHSBSP diagnostic categories. Cohen kappa was used to evaluate the agreement between the diagnosis on CNB and the final pathologic diagnosis in "clinically positive cases." Finally, a comparative analysis between the CNB method and fine needle aspiration biopsy was made. The distribution of our cases for each diagnostic category reflects the literature guidelines, with minor differences in the B2 and B4 groups. Statistical data about the patients' follow-up revealed a small number of false-negative cases in the B1 and B2 categories and no false-positive cases in the B4 and B5 groups. Uncertain malignant lesions (B3 category) were divided into 3 major areas (papillary lesions, fibroepithelial proliferations with cellular stroma, and intraepithelial atypical lesions such as ductal intraepithelial neoplasia grade 1/lobular intraepithelial neoplasia grade 1). Of the 29 patients in the B3 category, 26 underwent surgery. Cohen kappa analysis showed a strong statistical correlation (kappa = 0.77; Z = 4.3; significance >1.96; alpha = .05) between CNB diagnosis and surgical pathology final results in the subgroup of high-risk patients (diagnosis, >=ductal intraepithelial neoplasia grade 1 on CNB). Global diagnostic power of CNB in all 226 cases revealed high sensitivity (88.3%) and slightly lower specificity (72.8%). In 42 "doubtful" cases, synchronous fine needle aspiration biopsy and CNB were performed, showing a complementary role in the diagnostic phase of breast lesions. Core needle breast biopsy represents the criterion standard method in the diagnostic phase of many breast tumors; the NHSBSP classification is a useful reporting system that provides a good standardization of the pathologic diagnosis and provides a clear guideline for the correct management of the patient. PMID- 22056038 TI - Oncocytoma of the adrenal gland medulla. AB - We report an unprecedented case of an oncocytoma of the adrenal gland medulla in a 61-year-old woman. The patient presented with right flank pain and hematuria. Computed tomographic studies revealed a right adrenal gland mass that measured 2 cm, which was subsequently excised laparoscopically. Grossly, the tumor in the medulla measured 1.9 * 1.2 cm, weighed 5 g, and had a solid tan-brown cut surface. Histologically, it consisted of large tumor cells containing eosinophilic granular cytoplasm arranged in trabecular and nodular patterns. Electron microscopy revealed closely packed mitochondria in the cytoplasm of almost all tumor cells. The tumor cells were immunohistochemically positive for vimentin. The patient resumed usual activities 2 weeks after surgery, and at 6 month follow-up, she is doing well. PMID- 22056039 TI - Florid reactive lymphoid hyperplasia (lymphoma-like lesion) of the uterine cervix. AB - Lymphoma-like lesion (LLL) of the female genital tract is an older term in the literature that describes a florid reactive lymphoid proliferation that can be misinterpreted as lymphoma. Multiple causes of LLL have been suggested but most cases remain unexplained. We describe the clinicopathologic features of 6 patients with LLL involving the uterine cervix. Five patients presented with abnormal Papanicolaou test (Pap smear), and 3 patients had a biopsy procedure performed prior to detection of LLL in a loop electrosurgical excision procedure (LEEP). In each specimen, surface epithelial erosion was associated with a superficial, polymorphous lymphoid infiltrate with numerous scattered large cells, without cellular necrosis or sclerosis. Squamous dysplasia was present in 4 patients. Immunohistochemical studies revealed a mixed population of B- and T lymphoid cells. T-cells were more numerous but B-cells and formed aggregates or sheets in areas. The large cells were predominantly B-cells positive for CD20 and negative for CD3 in all cases. CD30 was positive 3 cases, and Epstein-Barr virus encoded RNA was positive in 3 cases. Assessment for clonality in 1 patient using polymerase chain reaction (PCR) methods revealed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements. At last clinical follow-up there was no evidence of progressive or systemic disease. We conclude that LLL of the cervix has a number of etiologies and that a prior surgical procedure, present in 3 patients in this study, is another possible etiology. As has been reported by others, monoclonal IgH gene rearrangements can be detected in this entity which has a benign clinical course. PMID- 22056040 TI - Aggressive meningiomas involving the parotid gland. AB - Parotid masses remain challenging secondary to the great diversity of primary tumors that may arise in the salivary glands and propensity for regional and even distant metastases to occur in this region. Meningioma must also be considered in the differential diagnosis of parotid masses, whether from direct extension, metastases, or as an extracranial primary. We herein report 4 cases of aggressive meningioma involving the parotid gland and the pathologic considerations in evaluating these tumors. PMID- 22056042 TI - Cardiac arrest due to long QT syndrome associated with excessive consumption of energy drinks. PMID- 22056041 TI - Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. AB - The ability to sequence genomes has far outstripped approaches for deciphering the information they encode. Here we present a suite of techniques, based on ribosome profiling (the deep sequencing of ribosome-protected mRNA fragments), to provide genome-wide maps of protein synthesis as well as a pulse-chase strategy for determining rates of translation elongation. We exploit the propensity of harringtonine to cause ribosomes to accumulate at sites of translation initiation together with a machine learning algorithm to define protein products systematically. Analysis of translation in mouse embryonic stem cells reveals thousands of strong pause sites and unannotated translation products. These include amino-terminal extensions and truncations and upstream open reading frames with regulatory potential, initiated at both AUG and non-AUG codons, whose translation changes after differentiation. We also define a class of short, polycistronic ribosome-associated coding RNAs (sprcRNAs) that encode small proteins. Our studies reveal an unanticipated complexity to mammalian proteomes. PMID- 22056043 TI - Applying the "Viskin test": QT interval in response to standing in elite athletes. PMID- 22056044 TI - A new diastolic heart sound secondary to free pulmonary regurgitation. PMID- 22056045 TI - Photooxidation of oxymyoglobin. Wavelength dependence of quantum yields in relation to light discoloration of meat. AB - The reaction quantum yield for photooxidation of oxymyoglobin to metmyoglobin in dilute aqueous solution and in beef extract has been determined for seven wavelengths of irradiation in the UV-visible region and, for aqueous solution, ranges from 1.6 x 10(-2) (254 nm) to 7 x 10(-6) (546 nm) mol einstein(-1). When taken together with the molar absorptivity at the wavelength of irradiation, the photooxidation quantum yield constitutes an objective measure of the effectiveness with which monochromatic light promotes the formation of metmyoglobin in meat. This is discussed in relation to light-induced discoloration of frozen meat. PMID- 22056046 TI - Bovine Longissimus dorsi muscle glycogen and color response as affected by dietary regimen and post-mortem electrical stimulation in young bulls. AB - Eighty bulls were assigned to one of two groups and fed a dietary regimen to defer or accelerate growth until slaughter. Bulls fed at an accelerated rate of growth (or high energy regimen) had higher post-mortem pH, and lower muscle glycogen stores, with darker lean color, and improved shear and palatability traits compared to deferred fed animals. Bulls fed at an accelerated rate of growth also had a higher degree of marbling and USDA quality grade. Electrical stimulation did not affect (P > 0.05) ultimate pH, but reduced (P < 0.05) glycogen values at 0 and 2 h post mortem. Electrical stimulation also improved muscle color, lowered cooking losses and improved the palatability of cooked longissimus dorsi steaks. PMID- 22056047 TI - Species identification of autoclaved meat samples using antisera to thermostable muscle antigens in an enzyme immunoassay. AB - An enzyme immunoassay (EIA) suitable for use in identification of cooked and autoclaved meat samples using antisera to thermostable muscle antigens (TMA) is described. Goat antisera to TMA of various species were tested against homologous and heterologous partially purified thermostable muscle antigens (PTMA) in an indirect EIA. Goat anti-eland and anti-cattle TMA sera were the poorest in differentiating other species PTMAs. Identification of various species PTMAs could be achieved using a battery of goat anti-TMA sera, where homologous goat anti-TMA serum fails to differentiate some of the PTMAs tested. PMID- 22056048 TI - Microbiological quality of sausages containing chickpea flour (Cicer arietinum). AB - English-type fresh skinless pork sausages in which 30% of the protein was replaced by unheated chickpea flour or by chickpea flour heated at 80 degrees C for 1 h were evaluated microbiologically. During storage at 0 degrees C, but not 22 degrees C, incorporation of unheated chickpea flour lowered the microbiological quality of the sausages, but incorporation of chickpea flour previously heated at 80 degrees C for 1 h led to no less of microbiological quality. PMID- 22056049 TI - Autofluorescence of adipose tissue measured with fibre optics. AB - The optical absorbance and fluorescence of porcine subcutaneous adipose tissue were measured directly with fibre optics. Either mercury or xenon light sources were used to illuminate tissue samples through one branch of a bifurcated light guide. Fluorescence was detected through the other branch of the light guide. Grating, prism and continuous interference filter monochromators were installed at appropriate locations in the light path and measurements were made with a computer-operated photomultiplier whose dynamic range was optimized at each wavelength measured. There was a small absorbance peak at 420 nm. With excitation at 365 nm, the peak of the fluorescence emission spectrum was at 510 nm with a secondary plateau from 430 to 450 nm. Proline powder and purified biochemical Type III collagen were also autofluorescent with a peak emission at 510 nm. Adipose cells associated with bovine heart valves were examined by fluorescence microscopy to obtain preparations containing adipose cells plus all three histological types of connective tissue fibres on the same section. Reticular fibres (around adipose cells) together with collagen and elastin fibres (in the heart valves) were all autofluorescent. It is suggested that the major source of adipose tissue fluorescence is from the reticular fibres that surround adipose cells, with minor contributions from other sources such as collagenous septa, vascular elastin and, possibly, cytoplasmic components. PMID- 22056050 TI - Effects of muscle pH on pressure-induced changes in the sarcoplasmic reticulum. AB - The effect of muscle pH on high pressure treatment of rabbit longissimus dorsi muscles has been studied by the use of pre-slaughter injections of epinephrine in order to vary the glycogen content and thus the extent of post-slaughter glycolysis in the muscles. Following pressure treatment the pH of the muscles varied between 5.9 and 7.1 while the control muscles varied between 6.6 and 7.1. The effects of the high pressure treatment on the ATPase activities, protein yield and protein composition of the sarcoplasmic reticulum (SR) were measured. The basal ATPase activity was not affected over this pH range while the extra ATPase activity, protein yield and protein composition of the SR were affected. The effects increased with decreasing pH. PMID- 22056051 TI - An assessment of the effects of an alternative method of carcass suspension and conditioning on the tenderness of beef. AB - The effects of leg-twisting treatment-making a slit in the flank, at the level of the cranio-ventral tip of the Rectus abdominis and tucking one hoof of the leg into this slit-plus 10 days ageing at 5-7 degrees C, on shear value, sarcomere length, fibre diameter and fragmentation score of Semimembranosus (SM) and Adductor (ADD) muscles were assessed in fifteen mature good grade White Fulani. The treatment and 10 days ageing significantly (P <= 0.05) lengthened the sarcomeres, reduced the fibre diameter, increased the fragmentation score and reduced the shear value of the oven-broiled SM and ADD samples. PMID- 22056052 TI - The influence of diet and time on feed on carcass traits and quality. AB - Seventy-two Simmental-sired steer calves (approximately 8 months old) were randomly assigned to one of two pre-finishing dietary treatments (low energy or high energy). Energy intake was monitored to produce average daily gains of approximately 0.41 (low energy) or 0.68 (high energy) kg during a 6-month growth interval. At 14 months of age the steers were assigned to four finishing (time on feed) groups-0, 56, 112 or 168 days. Steers assigned to the 0-day group received their respective pre-finishing diets from 14 to 20 months of age. The other groups received a finishing diet for the final 56, 112 or 168 days of the experiment. All steers were slaughtered at 20 months. Steers backgrounded on high energy diets produced heavier (P < 0.01), fatter (P < 0.01) carcasses with higher (P < 0.01) marbling scores and quality grades and LD steaks with greater (P < 0.05) ease of fragmentation, less (P < 0.05) detectable connective tissue and higher (P < 0.05) tenderness ratings as compared to steers on low energy diets. After 112 days on feed, quality grades were similar for high energy and low energy steers; however, tenderness ratings still favored the high energy treatment. Increased time on feed was associated with higher quality grades, but only within the low energy treatment group. Additionally, tenderness of LD steaks improved with increased time on feed; howver, the greatest improvement was observed from 0 to 56 days. PMID- 22056053 TI - Micro-organisms in food-2. Sampling for microbiological analysis: principles and specific applications ICMSF, Blackwell Scientific Publications, Oxford, 1986. 310 pp. Price: L19.50 (cloth). PMID- 22056054 TI - Usefulness of various biochemical and histochemical characteristics as indices of muscle type in lamb carcasses. AB - Contractile and metabolic characteristics of five different muscles from an homogeneous group of seven lambs were studied. Muscle typing was assessed by measuring myofibrillar ATPase and lactate deshydrogenase activities, myosin (FM1, FM2, FM3, SM1, SM2) and LDH (M(4), M(3)H, M(2)H(2), MH(3), H(4)) isoforms levels as well as fibre types composition (SO, SOG, FOG, FG). On this basis, muscles were classified as slow-twitch oxidative (diaphragm and supraspinatus), intermediate (triceps brachii), fast-twitch oxidative-glycolytic (longissimus dorsi) and fast-twitch glycolytic (tensor fascia latae). Discriminant factor analysis of data revealed that variables enabling a better discrimination of muscles (FG, SM1, FM2, FM1, H(4)) exhibited the lowest efficiency to discrimate animals. Furthermore, in contrast to LDH isoforms and fibre type composition subsets of variables, myosin isoforms analysis allowed a quite total identification of muscle classes since, 97.5% of the muscles were well ranged in their respective classes. Although animals were zootechnically similar, animal variability was important and animal effect was essentially detected through changes in the following set of variables: M(3)H, MH(3), SO and ATPase. PMID- 22056055 TI - Effect of dietary high-oleic sunflower oil on pork carcass traits and fatty acid profiles of raw tissues. AB - Ten gilts were randomly assigned to either a control sorghum-soybean diet or a similar diet containing 12% high-oleic sunflower oil (HOSO). No significant differences between the two groups were found in feedlot performance, carcass muscling and marbling score, but animals fed the HOSO diet had softer carcass fat and oilier carcasses than those fed the control diet. The ratio of monounsaturated fatty acids to saturated fatty acids (M/S) for subcutaneous fat increased from 1.58 in the control group to 3.76 in the HOSO group (138% increase); the M/S ratio for muscles (longissimus dorsi, semimembranosus and semitendinosus) increased from 0.96-1.19 to 1.84-1.88 (73% increase on an average). The percentage of polyunsaturated fatty acids in both adipose or muscle tissue was generally similar between the two diet treatments. PMID- 22056056 TI - Dimensional changes of isolated endomysia on heating. AB - The role of endomysial shrinkage in determining cooking loss was investigated directly by observations on the dimensional changes of isolated endomysial sheaths on heating up to 80 degrees C. Maximum shrinkage of 70% in diameter and 40% in length was observed, corresponding to a volume decrease of over 90%. The temperature at which half the maximal shrinkage occurs is in the range 52-61 degrees C. Minor differences in shrinkage behaviour were observed depending on the methods used to support the endomysia. The dimensional changes of the isolated endomysial sheaths are greater than those reported for whole meat. It is concluded that endomysial shrinkage has the potential to completely account for fluid expulsion from meat on cooking. PMID- 22056057 TI - Action of NaCl and polyphosphates in meat processing: Responses of myofibrils to concentrated salt solutions. AB - When meat is treated with salt, some parts of the meat are exposed to very high salt concentrations which then fall during equilibration. To gain a better understanding of the consequences of this treatment, we have observed the swelling and extraction of isolated myofibrils treated with series of salt solutions designed to mimic conditions found in salt-treated meat. Myofibrils swelled most in 1m (5.8%) NaCl and hardly at all in 5m (29%) NaCl. Similar results were obtained when the concentration of NaCl was raised in steps to 5m. The pronounced extraction of the A-band that occurs in 1m NaCl was decreased if higher NaCl concentrations were used instead. Lowering the concentration from higher values to 1m caused some swelling and extraction of the A-band, but not as much as when 1m was used directly. Inclusion of pyrophosphate in the solutions had marked effects. There was little swelling in 1m NaCl and none in 5m. Lowering the NaCl concentration to 1m from higher concentrations gave more swelling than observed when 1m was used directly. Extraction of the A-band was greatest in 1m, and was strongly inhibited in 5m. Myofibrils treated with 5m NaCl lost the ability to respond to the presence of pyrophosphate in 1m NaCl. The behaviour of myofibrils in high concentrations of NaCl alone is similar to that of pieces of meat. However, the persistent swelling of meat when the NaCl concentration is slowly raised to 5m is not found with myofibrils, suggesting that significant water compartments exist outside the myofibrils in such meat. PMID- 22056058 TI - The effect of vacuum packaging and gaseous atmosphere on microbial growth in tripe. AB - Changes in bacterial flora of tripe samples, stored at 4 degrees C in air, vacuum packaged or in a CO(2)-enriched atmosphere were studied. Aerobic plate counts showed a rapid increase in samples stored in air reaching a level of 1.6 * 10(9)/g from an initial level of 9.0 * 10(3)/g. The aerobic bacterial population inhibited in both vacuum packed and CO(2)-enriched atmosphere storage. The shelf lives of samples stored in air, under vacuum packaging or in gas mixtures, were 4, 8 and 9 days, respectively. Enterobacteriaceae and anaerobic counts tended to be higher under vacuum storage than in a CO(2)-enriched atmosphere. The numbers of lactic acid-producing bacteria were generally found to be lower under vacuum storage than in gas mixtures. PMID- 22056059 TI - Letter to the editor. PMID- 22056061 TI - The use of video image analysis for quantitative measurement of visible fat and lean in meat: Part 1-boneless fresh and cured meats. AB - The most accurate method of measuring fat content in meat is undoubtedly chemical analysis, but this can be both costly and time-comsuming. A system using a video camera and an image analyser has been used for rapid, non-destructive measurement of visible fat and lean in fresh boneless meats and meat products. Modifications to optics and illumination have improved the contrast, enhancing the separation between fat and lean areas in beef, lamb, pork and processed meats such as ham and bacon, resulting in improved fat and lean estimations compared with the system as originally supplied. Video image analysis (VIA) has been compared with fat area measurement by planimetry, weight of fat by dissection and with chemical analysis of fat in retail size cuts of meat such as chops and steaks. Comparison of VIA data with dissection and planimetry showed good correlation. There was also good agreement with chemical fat analysis. PMID- 22056060 TI - A pilot study of emergency medical technicians' field assessment of intoxicated patients' need for ED care. AB - OBJECTIVE: Alcohol-intoxicated individuals account for a significant proportion of emergency department care and may be eligible for care at alternative sobering facilities. This pilot study sought to examine intermediate-level emergency medical technician (EMT) ability to identify intoxicated individuals who may be eligible for diversion to an alternative sobering facility. METHODS: Intermediate level EMTs in an urban fire department completed patient assessment surveys for individual intoxicated patients between May and August 2010. Corresponding patient medical records were retrospectively reviewed for diagnosis, disposition, and blood alcohol content. Statistical analysis was conducted to determine correlates of survey response, diagnosis, and disposition; and survey sensitivity and specificity were calculated. RESULTS: One hundred ninety-seven patient transports and medical records were analyzed. Emergency medical technicians indicated 139 patients (71%) needed hospital-based care, and 155 patients (79%) had a primary ethanol diagnosis. Fourteen patients (7%) were admitted to the hospital, and EMTs identified 93% of admitted patients as requiring hospital based care. Overall sensitivity and specificity of the survey were 93% (95% confidence interval, 66.1-99.8) and 40% (95% confidence interval, 33.3-47.9), respectively. CONCLUSION: Intermediate-level EMTs may be able to play an important role in facilitating triage of intoxicated patients to alternate sobering facilities. PMID- 22056062 TI - Extrusion studies of mixtures containing certain meat offals: Part 1-Objective properties. AB - A study was made of thermoplastically extruded products prepared from soy grits incorporating varying percentages of offal. Beyond 35% incorporation no satisfactory extrudate could be prepared. A comparison was therefore made of the expansion ratio, density and hydratability of extrudates prepared from mixes containing 20% and 35% of bovine or porcine offal with those containing soy grit alone. The offal sources consisted of untreated or alkali-extracted bovine and porcine lung and bovine tripe (rumen and reticulum) and bovine tripe extracted by sodium dodecyl sulphate (SDS). Under the determined optimum operating conditions, extrudates from all offal/soy mixtures had lower expansion ratios and rehydratability than those from soy grits alone. Nevertheless, mixtures containing 20% or 35% alkali-extracted offal protein expanded more (greatest expansion at 170 degrees C), had lower density and greater hydratability than those containing these proportions of untreated offal or SDS-extracted offal protein. (The latter expanded most between 175-180 degrees C.) Whereas the incorporation of SDS-extracted bovine or porcine lung protein failed to yield textured extrudates, the incorporation of SDS-extracted bovine tripe protein at the 20% level did so. Effects due to source were otherwise small. PMID- 22056063 TI - Relationship between Ca(2+) release, sarcoplasmic Ca(2+), glycolysis and meat quality in halothane-sensitive and halothane-insensitive pigs. AB - Post-mortem assessment of porcine stress susceptibility and meat quality by measurements of mitochondrial calcium (content and rate of release), water holding capacity, pH at 1h post mortem and colour on M. longissimus dorsi confirm the usefulness of the halothane test for detecting stress susceptibility. Good correlations were observed between halothane sensitivity and meat quality. Post mortem samples of M. longissimus dorsi of halothane-sensitive pigs showed significantly higher levels of sarcoplasmic calcium than similar muscle from halothane-insensitive pigs. This strongly suggests that elevated sarcoplasmic calcium levels are linked to the formation of PSE meat. PMID- 22056064 TI - Pork carcass grading: A comparison of the New Zealand Hennessy Grading Probe and the Danish Fat-O-Meater. AB - The left sides from 224 pork carcasses were probed for fat thickness and muscle depth at four locations (last rib, and between the third and fourth, fourth and fifth, and fifth and sixth ribs posterior to the last rib) and at three positions (5, 7 and 9 cm off the dorsal mid-line) using the Hennessy Grading Probe (GP) and the Fat-O-Meater (FOM). In addition, fat thickness was recorded at the loin (8 cm off the dorsal mid-line) using both instruments, and the caliper of the FOM was used to measure fat thickness at three positions over the medial face of the M. gluteus medius on the dorsal mid-line of the carcass. All pork sides were cut into five North American primals which were subsequently separated into fat, bone and lean to define percentage lean yield. The range in warm carcass weight and percentage lean yield varied from 58.5 to 94.5 kg and from 29.60 to 48.91%, respectively. The two probes differed little in precision for the prediction of percentage lean yield. Measurements taken with the GP and FOM between the third and fourth, and fourth and fifth last ribs gave the lowest residual errors. Position of measurements (5, 7 or 9 cm) had little effect on the relationship between lean yield and fat thickness or fat thickness and muscle depth. Addition of a second measurement fat thickness or muscle depth, provided only minor improvement in precision for the prediction of percentage lean yield over that of a single fat thickness measurement. The results suggest that, for grading systems using percentage lean yield as a basis, both the GP and FOM would provide similar precision, and that the choice of an instrument would then depend more on its durability and performance under commercial conditions. PMID- 22056065 TI - Use of histidine dipeptides to estimate the proportion of pig meat in processed meats. AB - High performance liquid chromatography on a Partisil-10 SCX column was examined as an alternative to conventional ion exchange chromatography as a means of quantitating the histidine dipeptides, anserine, carnosine and balenine in processed pig meats. Because the ratio of these dipeptides in skeletal muscle of the pig is different from that in other species commonly used for meat, it is possible to estimate the proportion of pig meat in processed meats. Several Australian pork products were found to contain a low proportion of lean pig meat. PMID- 22056066 TI - Letter to the editor. PMID- 22056067 TI - Reducing xerostomia after chemo-IMRT for head-and-neck cancer: beyond sparing the parotid glands. AB - PURPOSE: To assess whether, in addition to sparing the parotid glands (PGs), xerostomia after chemotherapy plus intensity-modulated radiotherapy (chemo-IMRT) for head-and-neck cancer is affected by reducing the dose to the other salivary glands. PATIENTS AND METHODS: In a prospective study, 78 patients with Stage III IV oropharynx/nasopharynx cancer underwent chemo-IMRT, with the aim of sparing the parts of the bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) outside the target (when contralateral level I was not a target). Before therapy and periodically for 24 months, validated patient-reported xerostomia questionnaire (XQ) scores and observer-graded xerostomia scores were recorded. Also, the stimulated and unstimulated saliva was measured selectively from each of the PGs and SMGs. The mean OC doses served as surrogates of minor salivary gland dysfunction. Regression models assessed the XQ and observer-graded xerostomia predictors. RESULTS: Statistically significant predictors of the XQ score on univariate analysis included the OC, PG, and SMG mean doses and the baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. The OC, PG, and SMG mean doses were moderately intercorrelated (r = 0.47-0.55). On multivariate analyses, after adjusting for the PG and SMG doses, the OC mean dose (p < .0001), interval from RT (p < .0001), and stimulated PG saliva (p < .0025) were significant predictors of the XQ scores and the OC mean dose and time for observer-graded xerostomia. Although scatter plots showed no thresholds, an OC mean dose of <40 Gy and contralateral SMG mean dose of <50 Gy were each associated with low patient-reported and observer-rated xerostomia at almost all post-therapy points. CONCLUSION: The PG, SMG, and OC mean doses were significant predictors of both patient-reported and observer-rated xerostomia after chemo IMRT, with OC doses remaining significant after adjusting for the PG and SMG doses. These results support efforts to spare all the salivary glands by IMRT, beyond the PGs alone. PMID- 22056068 TI - Carbon ion irradiation inhibits glioma cell migration through downregulation of integrin expression. AB - PURPOSE: To investigate the effect of carbon ion irradiation on glioma cell migration. METHODS AND MATERIALS: U87 and Ln229 glioma cells were irradiated with photons and carbon ions. Migration was analyzed 24 h after irradiation. Fluorescence-activated cell sorting analysis was performed in order to quantify surface expression of integrins. RESULTS: Single photon doses of 2 Gy and 10 Gy enhanced alpha(nu)beta(3) and alpha(nu)beta(5) integrin expression and caused tumor cell hypermigration on both vitronectin (Vn) and fibronectin (Fn). Compared to integrin expression in unirradiated cells, carbon ion irradiation caused decreased integrin expression and inhibited cell migration on both Vn and Fn. CONCLUSION: Photon radiotherapy (RT) enhances the risk of tumor cell migration and subsequently promotes locoregional spread via photon induction of integrin expression. In contrast to photon RT, carbon ion RT causes decreased integrin expression and suppresses glioma cell migration on both Vn and Fn, thus promising improved local control. PMID- 22056069 TI - Percentage of cancer volume in biopsy cores is prognostic for prostate cancer death and overall survival in patients treated with dose-escalated external beam radiotherapy. AB - PURPOSE: To investigate the prognostic utility of the percentage of cancer volume (PCV) in needle biopsy specimens for prostate cancer patients treated with dose escalated external beam radiotherapy. METHODS AND MATERIALS: The outcomes were analyzed for 599 men treated for localized prostate cancer with external beam radiotherapy to a minimal planning target volume dose of 75 Gy (range, 75-79.2). We assessed the effect of PCV and the pretreatment and treatment-related factors on the freedom from biochemical failure, freedom from metastasis, cause-specific survival, and overall survival. RESULTS: The median number of biopsy cores was 7 (interquartile range, 6-12), median PCV was 10% (interquartile range, 2.5-25%), and median follow-up was 62 months. The PCV correlated with the National Comprehensive Cancer Network risk group and individual risk features, including T stage, prostate-specific antigen level, Gleason score, and percentage of positive biopsy cores. On log-rank analysis, the PCV stratified by quartile was prognostic for all endpoints, including overall survival. In addition, the PCV was a stronger prognostic factor than the percentage of positive biopsy cores when the two metrics were analyzed together. On multivariate analysis, the PCV predicted a worse outcome for all endpoints, including freedom from biochemical failure, (hazard ratio, 1.9; p = .0035), freedom from metastasis (hazard ratio, 1.7, p = .09), cause-specific survival (hazard ratio, 3.9, p = .014), and overall survival (hazard ratio, 1.8, p = .02). CONCLUSIONS: For patients treated with dose escalated external beam radiotherapy, the volume of cancer in the biopsy specimen adds prognostic value for clinically relevant endpoints, particularly in intermediate- and high-risk patients. Although the PCV determination is more arduous than the percentage of positive biopsy cores, it provides superior risk stratification. PMID- 22056070 TI - Changes in the nature of phenolic deposits after re-warming as a result of melatonin pre-sowing treatment of Vigna radiata seeds. AB - Changes in phenolics (PhC - phenolic compounds) measured as UV-absorbing compounds (UVAC) and their localization as well as growth, lipid peroxidation (TBARS level) and proline (Pro) level in three-day-old roots of seedlings (T(o) stage) obtained from hydroprimed (H) and hydroprimed with melatonin (H-MEL) seeds after 2 days of chilling (5 degrees C) and 2 days of re-warming were examined. H and H-MEL resulted in inhibition of root growth under optimal conditions, but after re-warming, a positive effect of MEL was noted. The results also showed a positive MEL impact on TBARS level already after chilling and especially after re warming. Exposure of Vigna radiata seedlings to chilling caused a significant increase in Pro level, especially in H-MEL roots, but after re-warming it drastically decreased. Under chilling stress, accumulation of UVAC also decreased. However, after re-warming it returned to the level observed in the roots grown constantly at 25 degrees C. Even if after re-warming of V. radiata seedlings only slight accumulation of total PhC was observed, phenolic deposits accumulating in the vacuoles of H-MEL roots were completely different from those in the vacuoles of the control and H roots. H-MEL application to the seeds resulted in a significant increase in small granular composite materials, while in the control and H roots, large oval deposits prevailed. Taken together, it is probable that all of these differences were connected with positive effects of MEL on chilled V. radiata seedlings after re-warming. PMID- 22056071 TI - Transgenic tobacco plants expressing ectopically wheat H+-pyrophosphatase (H+ PPase) gene TaVP1 show enhanced accumulation and tolerance to cadmium. AB - Cadmium (Cd) is considered an extremely significant pollutant due to its high toxicity to many organisms. Plants have evolved several mechanisms to cope with Cd, the most important of which is vacuolar sequestration. Cadmium can be directly transported into vacuoles by cations/H(+) exchangers, such as CAXs, which are energized by the pH gradient established by proton pumps. A cDNA (TaVP1) encoding wheat vacuolar H(+)-pyrophosphatase (V-H-PPase) was ectopically expressed in transgenic tobacco to evaluate whether this proton pump expression would enhance Cd tolerance and accumulation in planta. When TaVP1-expressing plants were exposed to various concentrations of Cd, they were found to be more tolerant to Cd compared to wild type plants. Cadmium accumulation in the plant biomass in transgenic plants was higher than that in wild type plants. To the best of our knowledge, this is the first report on the potential for enhancing proton pump expression as a strategy to improve Cd tolerance and accumulation in plants. PMID- 22056072 TI - Double-antibody ELISA for detection of trace amounts of pig meat in raw meat mixtures. AB - A modification of double-antibody sandwich ELISA (enzyme-linked immunosorbent assay) has been applied successfully to the problem of the detection of very low amounts of pig meat (1-3%) in beef and manufactured beef products made with rusk and other additives. The assay uses a monospec fic antiserum bound to the solid plastic support to sequester the porcine serum albumin (PSA) from amongst the many proteins co-extracted from the complex sample extracts. Further immuno recognition was made with a second antibody, also specific for PSA, which was detected by a conjugated enzyme anti-IgG that interacted only with the second anti-PSA antibodies. Subsequent enzymic conversion of substrate gave clear visual differences between beef and beef containing 0.5% of pig meat and beef products with 1% of the lean replaced by lean pork compared with reference samples. PMID- 22056073 TI - The relationship between water-holding capacity and cooked meat tenderness in some beef muscles as influenced by acidic conditions below the ultimate pH. AB - Previous studies have indicated the beneficial influence of higher than normal ultimate pH (pH(u)) on the tenderness of cooked meat. Such benefits have been indirectly linked to the influence of increased pH on the water-holding capacity (WHC) of meat above the iso-electric point (IEP) of the myofibrillar proteins. In the present study, relationships between WHC and the tenderness of some beef muscles were investigated under pH conditions within and below the IEP of the myofibrillar proteins, such that the maximum range of meat swelling was achieved. It was found that increased WHC, as measured by swelling ratio in both raw and cooked meat, markedly influenced cooked meat tenderness, irrespective of the connective tissue content of the muscles. The results fitted a series of exponential decay equations relating swelling ratio to cooked meat toughness. Additionally, strong linear decreases in toughness were apparent over the pH range 4.6 to 4.1 for the three muscle types studied. PMID- 22056074 TI - Nutritional evaluation of sausages containing chick pea flour (Cicer arietinum). AB - Nutritional evaluation of protein quality was carried out on English-type fresh skinless pork sausages in which 30% of the protein had been replaced by chick pea flour. Net protein utilisation, biological value and protein efficiency ratio were unaffected by 30 % meat protein replacement. Comparison of the amino acid composition with the biological values suggested some reduction in amino acid availability due to cooking. PMID- 22056075 TI - Physical, chemical, histological and palatability characteristics of muscles from three breed-types of cattle at different times-on-feed. AB - Forty-five steers (9-12 months of age) of Angus (n =15), Brahman (n = 15) and Brahman * Angus (n = 15) breed-types were fed a high-energy diet and then slaughtered after 0, 112 or 224 days of feeding. At 7 days post mortem, the M. longissimus and M. biceps femoris were removed from the left side of each carcass and steaks were obtained for determination of sensory panel ratings, Warner Bratzler shear force, sarcomere length, collagen content and collagen solubility. Tenderness ratings of steaks from the M. longissimus and M. biceps femoris from Angus were generally higher than ratings for steaks from Brahman or Brahman * Angus steers. Steaks from Brahman * Angus received higher tenderness ratings than steaks from Brahman steers in only a few comparisons. The three breed-types of cattle responded to time-on-feed differently; Brahman cattle needed to have been fed longer than Angus cattle to produce equally tender beef. With increased time on-feed, M. longissimus tenderness increased for all breed-types, but M. biceps femoris tenderness was not related to time-on-feed. Few significant differences were observed among breed-types and among time-on-feed periods for collagen content or collagen solubility. Tenderness differences were closely correlated with the contractile state of the muscle which, in turn, was associated with weight, subcutaneous fat thickness and temperature decline of the carcass. PMID- 22056076 TI - Accelerated dry curing of hams. AB - Uncured pork legs from the right side of 18 carcasses were treated with a Ross Tenderizer and the left side were controls. All 36 samples were dry-cured for 40, 56 or 70 days and evaluated for appearance traits, cure penetration characteristics, microbial load, Kramer Shear force and taste attributes. The tenderization treatment had no effect (P > 0.05) on visual color or cure penetration rate, weight loss before curing, percentage moisture, nitrate level, nitrite level, total plate count, anaerobic counts, psychrotrophic counts, objective and subjective tenderness measurements or juiciness. However, the higher values of salt suggested a possible acceleration of the dry cure penetration process among the tenderized samples. Cure time had no effect (P > 0.05) on percentage moisture, percentage salt, nitrate content, nitrite content, shear force and juiciness. Results suggest a limited effect of the mechanical tenderization process on certain traits related to dry curing and that total process time should be at least 70 days if color stability during cooking is desired. PMID- 22056077 TI - Pegylated liposomal doxorubicin as first-line monotherapy in elderly women with locally advanced or metastatic breast cancer: novel treatment predictive factors identified. AB - We investigated the efficacy and safety of single-agent pegylated liposomal doxorubicin (PLD) as first-line treatment for elderly women with advanced breast cancer and evaluated predictive markers for response and toxicity. Twenty-five women >= 65 years received 40 mg/m(2) PLD every 28 days. Time to treatment failure (TTF), response rate, time to progression (TTP) and overall survival (OS) was calculated. The ABCB1 single nucleotide polymorphisms (SNP), tumor MRN complex, and TOPOIIalpha were analyzed. A mean of 7.4 cycles PLD were administered and TTF was 5.5 months and OS 20.6 months. ABCB1 SNPs were found to correlate to both efficacy and toxicity, while tumor expression of the MRN complex and TOPOIIalpha correlated to TTP. PLD is a safe and effective treatment for elderly breast cancer patients. Also potential predictive markers were identified. PMID- 22056078 TI - Reactive oxygen species and p38 MAPK regulate Bax translocation and calcium redistribution in salubrinal-induced apoptosis of EBV-transformed B cells. AB - Salubrinal is a specific eIF2alpha phosphatase inhibitor that inhibits ER stress mediated apoptosis. However, maintaining hyper-phosphorylated eIF2alpha state with high doses of salubrinal treatment promotes apoptosis in some cancer cells. In this report, we found that salubrinal induced apoptosis of EBV-transformed B cells. Notably, salubrinal induced ROS generation and p38 MPAK activation, which then induced expression of FasL. Moreover, salubrinal subsequently led to activation of caspases, calcium redistribution, Bax translocation, cytochrome c release, and apoptosis. These findings suggest that salubrinal may be a novel therapeutic approach for EBV-associated malignant diseases. PMID- 22056079 TI - [Prevalence of proteinuria and its association with HIV/AIDS in Congolese children living in Kinshasa, Democratic Republic of Congo]. AB - CONTEXT: In Sub-Saharian Africa, the extent of the HIV-related kidney diseases is less known. Even so, that region is supposed to be the epicentre of such complications. This study aimed to determine the prevalence of proteinuria in Congolese children living in Kinshasa and to study its association with the HIV infection. METHODS: By a cross-sectional and multicentric study (in six hospitals of Kinshasa), 194 children were consecutively recruited from August 2008 to February 2009. Among these, 101 naives HIV-infected children and 93 HIV uninfected children like a control group. Proteinuria was assessed using urine dipstick completed by the 24-hour proteinuria assessment (Esbach method). Determinants of proteinuria were assessed by logistic regression. RESULTS: The median age of all children recruited was 84 months (9-221 months). Concerning the HIV-infected children, the median age was 76 months (9-221 months) with a male/female ratio of 1/1. The prevalence of proteinuria in this group was in order to 23.8%. HIV infected children have seven times more probability to present proteinuria than non infected children (OR 6.9; IC 95%: 2.3-20.8; P<0.001). Important immunosuppression was the main determinant of proteinuria (OR 10.4; IC 95%: 3.34-32.48; P<0.001). CONCLUSION: Proteinuria is common in Congolese children. The HIV infection rises significantly the probability to present proteinuria in children of this study, more so among those with important immunosuppression. This raises the question about the ideal time to initiate HAART in order to reduce the prevalence of kidney injury and to provide the best outcome. PMID- 22056080 TI - [Cell therapy in autoimmune diseases]. PMID- 22056081 TI - Adsorption of surfactin produced from Bacillus subtilis using nonwoven PET (polyethylene terephthalate) fibrous membranes functionalized with chitosan. AB - This article deals with an alternative method for bio-separation of surfactin produced by Bacillus subtilis using sorption method on nonwoven PET (polyethylene terephthalate) fibrous membranes functionalized with chitosan. In the first part of the study, surface functionalization of the PET nonwoven fibrous membranes is carried out with aqueous 65% deacetylated chitosan solution with or without a prior surface activation using air-atmospheric plasma treatment. Very small modification of the PET fibrous nonwoven air-permeability confirms the functionalization of PET fibre surface with little reduction of membrane porosity. The functionalized membranes are then characterized by physico-chemical methods: X-ray Photoelectron Spectroscopy (XPS), Wettability and zeta potential. Chitosan increases drastically the zeta potential of PET at all pH values though a prior plasma treatment of the PET membrane reduces slightly the increase in zeta potential values. Sorption of surfactin quantified by HPLC shows that the extent of surfactin sorption on PET nonwovens depends on the surface functionalization method. Surface functionalization with chitosan results in immediate sorption of the entire quantity of surfactin. A prior surface activation by air atmospheric plasma treatment of the PET membranes before chitosan application retards the sorption of entire surfactin which takes place after 1.5h, only. Increased zeta potential and increased hydrophobic behavior in the presence of chitosan without plasma activation would explain the interesting surfactin sorption results. PMID- 22056082 TI - Adsorption induced enzyme denaturation: the role of protein surface in adsorption induced protein denaturation on allyl glycidyl ether (AGE)-ethylene glycol dimethacrylate (EGDM) copolymers. AB - The effects of protein size on adsorption and adsorption-induced denaturation of proteins on copolymers of allyl glycidyl ether (AGE)-ethylene glycol dimethacrylate (EGDM) have been studied. Different responses were observed for the amount of protein adsorbed and denatured on the polymer surface for different proteins (trypsin, alchol dehydrogenase from baker's yeast (YADH), glucose dehydrogenase (GDH) from Gluconobacter cerinus, and alkaline phosphates from calf intestinal mucosa (CIAP). Protein adsorption on the copolymer with 25% crosslink density (AGE-25) was dependent not only on the size of the protein but also on the presence of glycoside residues on the protein surface. Adsorption and denaturation of proteins follows the order YADH>trypsin>GDH>>CIAP although the molecular weights of the proteins follow the order YADH>CIAP>GDH>trypsin. The lack of correlation between amount of adsorbed protein and its molecular weight was due to the presence of glycoside residues on CIAP and GDH which protect the enzyme surface from denaturation. Enzyme stabilities in aqueous solutions of 1 cyclohexyl-2-pyrrolidinone (CHP) correlate well with the trend in denaturation by the copolymer, strongly suggesting that hydrophobic interactions play a major role in protein binding and the mechanism of protein denaturation is similar to that for water-miscible organic solvents. PMID- 22056083 TI - Cellular fusion and whitening effect of a chitosan derivative coated liposome. AB - In this study, a derivative of chitosan, N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), was coated onto the liposomes made of cholesterol and 1,2-palmitoyl-sn-glycero-3-phosphatidylcholine (DPPC). These coated liposomes were loaded with kojic acid for skin whitening. The appearance of liposome was examined using transmission electron microscope (TEM), and the coating of HTCC to the liposome was confirmed by infrared spectroscopy. By labeling with Dil, the fusion of liposome with the cell membrane of L929 fibroblast and B16-F10 melanoma was improved by the coating of HTCC. Based on the results of Franz cell experiment, the penetration of kojic acid (KA) through skin was improved by using HTCC-coating liposomes. Furthermore, the cell proliferation of L929 was not affected by HTCC-coating liposomes, while that of B16-F10 was reduced slightly with the increase of the concentration of HTCC-loading liposome. The degree of skin whitening was determined based on the melanin content in B-16 F10 cells. The results showed that the level of melanin synthesis was lower when KA was delivered using HTCC-coating liposome instead of traditional liposome. PMID- 22056084 TI - Sol-gel network silica/modified montmorillonite clay hybrid nanocomposites for hydrophobic surface coatings. AB - Sol-gel silica/nanoclay composites were prepared through sol-gel polymerization technique using tetraethylorthosilicate precursor and montmorillonite (MMT) clay in aqueous media. In this study, both montmorillonite-K(+) and organically modified MMT (OMMT) clays were used. The prepared composites were coated on glass substrate by making 1 wt% solution in ethyltrichlorosilane. The incorporation of nanoclay does not alter the intensity of characteristic Si-O-Si peak of silica network. Thermogravimetric studies show that increasing clay content increased the degradation temperature of the composites. Differential scanning calorimetry (DSC) results of organically modified MMT nanoclay incorporated composite show a shift in the melting behavior up to 38 degrees C. From DSC thermograms, we observed that the DeltaH value decreased with increasing clay loading. X-ray diffraction patterns prove the presence of nanoclay in the composite and increase in the concentration of organically modified nanoclay from 3 to 5 wt% increases the intensity of the peak at 2theta=8 degrees corresponds to OMMT. Morphology of the control silica gel composite was greatly influenced by the incorporation of OMMT. The presence of nanoclay changed the surface of control silica gel composite into cleaved surface with brittle in nature. Contact angle measurements were done for the coatings to study their surface behavior. These hybrid coatings on glass substrate may have applications for hydrophobic coatings on leather substrate. PMID- 22056085 TI - In vitro evaluation of the effects of electrospun PCL nanofiber mats containing the microalgae Spirulina (Arthrospira) extract on primary astrocytes. AB - The blue-green microalgae, Spirulina, a harmless food and pharmaceutical additive, has several bioactive compounds that have therapeutic functions. Polycaprolactone (PCL) is a biocompatible and biodegradable polymer that has widely been used for tissue engineering. The electrospun PCL nanofiber containing Spirulina (PCL-Spirulina) was fabricated and tested as a potential extracellular matrix material for a culture of primary astrocytes, which play important roles in CNS injured systems. Spirulina extract was observed to increase growth and metabolic activity of rat primary astrocytes without any harm once added to the culture media. However, PCL-Spirulina nanofiber was proven to alleviate astrocyte activity. Through this research and to the best of our knowledge, we first suggest a novel composite nanomaterial, an electrospun PCL-Spirulina nanofiber that could be used to treat CNS injured systems. PMID- 22056086 TI - Modulation of the heterogeneous senescence of human mesenchymal stem cells on chemically-modified surfaces. AB - Human mesenchymal stem cells (hMSCs) are multipotent and have been recognized as a source for tissue engineering or cell therapy. It is, therefore, imperative to develop methods to acquire enough hMSCs that maintain self-renewal and differentiation potential. However, aged hMSCs are prone to have a gradual decline in differentiation and proliferation potential with continual cell cycle divisions during in vitro culture. The physiochemical properties of hMSCs are highly dependent on their micro-environment, i.e. the 'stem cell niche'. In this study, the heterogeneous aging of hMSC was examined on chemically defined self assembly monolayer surfaces. Surface energy was shown to regulate aged hMSC morphology, survival, and proteoglycan expression. High surface energy supplied a preferable environment for hMSC survival and expression of proteoglycans. These results will prove valuable to the design of scaffolds for tissue engineering or for the modulation of implantation environments. PMID- 22056087 TI - Submucosal tunneling endoscopic resection: a new technique for treating upper GI submucosal tumors originating from the muscularis propria layer (with videos). PMID- 22056088 TI - Individual and contextual bases of thriving in adolescence: a view of the issues. AB - We introduce this special issue on the individual and contextual bases of adolescent thriving by describing the relational developmental systems theory based, positive youth development (PYD) perspective that frames much of contemporary research about health and positive development across the adolescent period and that, more specifically, frames the 4-H Study of PYD, the data set from which the empirical work in this special issue is drawn. All articles point to the combined role of characteristics of the person and ecological assets in the family, school, or community settings of youth to promote the development of PYD. We discuss how these articles provide evidence about the empirical usefulness of the PYD perspective and discuss how research testing the PYD model has new and important implications for both adolescent development research and for the application of developmental science. PMID- 22056089 TI - Plasma selenium concentrations in pregnant women in two countries with contrasting soil selenium levels. AB - PROJECT: Selenium has an important role in antioxidant defense and cell mediated immunity. Plasma selenium is a useful biomarker for comparing selenium status across populations, and influenced by selenium levels of soils and plants. PROCEDURE: This cross-sectional study compared plasma selenium (by electrothermal atomic absorption spectrophotometry) of women at 24 weeks gestation in Malawi (n=152) and the Philippines (n=301), countries with low and high soil selenium levels, respectively. Data on anthropometry, smoking, intakes of energy, nutrients and food groups (via 24-h recalls), hemoglobin, serum zinc, and C reactive protein (CRP) were also collected. RESULTS: Mean (95% CI) plasma selenium was lower for Malawian than Filipino women (0.79, 0.77, 0.82 MUmol/L vs. 1.44, 1.41, 1.47 MUmol/L; p<0.001); 83% had concentrations below 1.0 MUmol/L compared to 3% in the Filipinos. Cereals provided 78% and 67% of the energy in Malawi and the Philippines, respectively compared to 4% and 8.5%, respectively for cellular animal protein. Plasma selenium was correlated modestly with BMI (r= 0.138; p=0.096) and elevated CRP (>5.0 mg/L) (r=-0.143; p=0.084) in Malawi, and significantly with intake of cellular animal protein (g/d) (r=0.23; p=0.020) and serum zinc (r=0.13; p=0.044) in the Philippines. No comparable relationships were observed in either group for smoking, hemoglobin, or cereal intakes. CONCLUSION: Differences in plasma selenium paralleled reported trends in selenium concentrations in soils and staple cereals in Malawi and the Philippines. The biological significance of the lower plasma selenium for the Malawian women, and the extent to which they pose a risk for fetal and neonatal development, is uncertain. PMID- 22056090 TI - Analysis of Warner-Bratzler shear pattern with regard to myofibrillar and connective tissue components of tenderness. AB - Force-deformation curves from the Warner-Bratzler (WB) shear device were used to evaluate specific changes in the myofibrillar (WB M-force) and connective tissue component (WB C-force) of tenderness in samples from beef semitendinos. Cores were heated in a water bath to end point temperatures of 60 degrees C and 80 degrees C by using combinations of slow and fast heating rates. Increasing the end point temperature from 60 degrees C to 80 degrees C was found to increase the WB M-force and to decrease the WB C-force, whereas the WB peak force was least affected. Comparisons between different heating rate combinations to samples heated to 80 degrees C showed that the WB M-force was affected by a heating rate both below and above 60 degrees C, while the WB C-force was most influenced by a heating rate above 60 degrees C. Slower heating rates and higher endpoint temperatures resulted in greater cooking losses and increased solubility of collagen. The WB M-force and WB C-force were found to be more significant estimators of sensory evaluations of tenderness and collagen solubility in this experiment than the usually measured WB peak force. PMID- 22056091 TI - Comparison of methods for measuring sarcomere length in beef semitendinosus muscle. AB - The objective of the study was to compare the precision of the laser method for measuring sarcomere length with the precision of two oil-immersion microscope methods. Eighteen semitendinosus muscles were assigned to one of three post mortem treatments to provide a wide range in sarcomere length. Two 5.0cm sections were removed from the centre of each muscle. Each section was subdivided into six equal-size pieces and randomly allotted to each of three participating institutions. Analysis of variance revealed that sarcomere length measurement was not significantly affected by the method of measurement or by the technician. For 99% precision, the laser method required 34 measurements, whereas the two microscope methods required 45 and 66 measurements, respectively. PMID- 22056092 TI - Anoxic storage of fresh beef. 2: Colour stability and weight loss. AB - Storage variables, such as age of meat, temperature and humidity of storage, and commercial preparation of meat, were evaluated for their effects on the colour stability and weight loss of fresh beef packaged in anoxic gas atmospheres. Apart from age of meat post mortem, increasing storage temperature has the most marked effect on reducing colour stability and increasing weight loss. Temperature effects on colour stability and weight loss for individual muscles have interesting similarities; the extent of the temperature effect on both these qualities of meat is M. psoas major >M. gluteus medius >M. semimembranosus. The significance of such similarities in terms of differing physical and biochemical characteristics of muscles is discussed. PMID- 22056093 TI - Sensory assessment of fatness and conformation of beef steers. AB - Human judgement, based on looking, handling and experience, still plays an important part in choosing beef animals for various purposes. This paper describes an attempt at a scientific investigation of the method. Two groups of steers-(a) sixteen Aberdeen Angus and (b) thirty Herefords-were assessed by different panels of judges for fatness and conformation, regionally and overall. Repeat assessments were made on the group (a) animals. The carcasses were assessed by the same panels, then dissected into component tissues. On the basis of discrimination and consistency tests and correlation with dissection data a best panel was chosen for the group (a) animals. It was found that judges were very effective in ranking animals within the total sample but, contrary to intuitive ideas, the average score was better related to quantities of dissected tissues than the score of any individual, which makes the method more expensive than might be thought. PMID- 22056094 TI - Effect of pressure treatment on the sarcoplasmic reticulum of red and white muscles. AB - The effects of high pressure (150 MPa) on the sarcoplasmic reticulum of red and white muscles have been studied. When whole muscle is pressurised either pre rigor or post-rigor the major effect on the SR is the loss of extra ATPase activity and the loss of several proteins including the 100,000 dalton ATPase and calsequestrin. When isolated SR is pressurised the extra ATPase activity is lost but there is no protein degradation. Measurements of muscle pH and the influence of pH on pressurisation effects indicate active proteolysis in white muscle when it is pressurised. In all these studies the basal ATPase activity was relatively unaffected. The effect of pressure treatment on the yield of SR protein varied with different muscles, being greatest in the muscles which had the highest concentration of extra ATPase and calcium uptake activities. These muscles also reached the lowest pH during pressurisation, thus favouring proteolysis. PMID- 22056095 TI - Pressure treatment of meat: Effects on thermal transitions and shear values. AB - The effects of pressure treatment (150 MN m(-2) for 3 h at 0 degrees C) on the pH, thermal transitions, ultrastructure and Warner-Bratzler shear values of post rigor beef semimembranosus and longissimus dorsi muscles have been investigated. Pressure treatment resulted in a slight but significant increase in pH. Differential scanning calorimetry revealed large changes in the thermograms of muscle samples as a result of pressure treatment, in particular a transition attributed to F-actin was absent in the pressure-treated sample. Examination of the ultrastructure also revealed extensive change as a result of pressure treatment, particularly in the I-band and M-line region. Pressure treatment either did not change shear values or increased them, according to whether the muscle was in the stretched or contracted state, respectively. The results are thought to support a theory for contraction state toughness proposed by Voyle (1969) in which increasing toughness is caused by an increasing incidence of sarcomeres in which thick filaments have been compressed onto the Z-line, thus removing the I-band as a zone of weakness. PMID- 22056096 TI - Can muscle lysosomal enzymes affect muscle collagen post-mortem? AB - Incubation of collagen fibres with muscle lysosomal enzymes at 37 degrees C, pH 5.5, affects significantly the thermal stability of muscle collagen. The thermolabile fraction increases and the strength of the fibres measured through thermal contraction decreases by/nearly 50% after treatment. It is concluded that the muscle lysosomal fraction contains an enzyme system which can reduce the strength of muscle collagen at pH 5.5. The reason why this potential is not exhibited post-mortem could be due to a limited release of the enzymes or the presence of enzyme inhibitors. PMID- 22056097 TI - Lytic lesion. PMID- 22056098 TI - Controversies in family planning: management of lethal fetal anomalies in the third trimester. PMID- 22056099 TI - Controversies in family planning: first trimester uterine evacuation for the anticoagulated patient. PMID- 22056100 TI - Comparison of medical abortion follow-up with serum human chorionic gonadotropin testing and in-office assessment. AB - BACKGROUND: The study was conducted to compare lost to follow-up (LTFU) rates in women having a medical abortion who chose follow-up by in-office ultrasound assessment or serum beta human chorionic gonadotropin (beta-hCG) testing. METHODS: This retrospective chart review included 865 women who underwent medical abortion in a free-standing outpatient clinic from September 1, 2007, through September 30, 2010. Patients had a 1-week follow-up evaluation after receiving the medications consisting of in-office ultrasound assessment or serial serum beta-hCG testing. Ultrasound assessment was offered throughout the study period, and serum beta-hCG testing was offered as of September 1, 2008. Demographic and medical data were reviewed to evaluate LTFU rates based on patient's chosen method of follow-up. Multivariable logistic regression analysis was performed to evaluate factors that were independently associated with lack of follow-up. RESULTS: LTFU rates increased from 18% to 27% in the first and third years of the study period, respectively (p=.009). LTFU rates with ultrasound and beta-hCG testing were 22.9% and 33.7%, respectively (p=.024). In multivariable analysis, follow-up method was not associated with increased LTFU. Increased parity, any previous induced abortion, increased distance from home to clinic site and unemployment were independently associated with increased LTFU. CONCLUSIONS: Although LTFU rates are higher with serum beta-hCG testing than in-office ultrasound follow-up in our patient population, the women who choose this method are inherently more likely not to follow-up because of other characteristics that predict a high likelihood of being LTFU. Offering serum beta-hCG testing does not decrease the LTFU rate in women having a medical abortion. PMID- 22056101 TI - Surface properties of muscle protein extracts. AB - The interfacial properties of proteins extracted from muscle using salt solutions of different concentration and for different extraction times were determined by the drop volume method. At a bulk phase concentration of 10(-2) wt%, it appears that the sarcoplasmic-rich fraction of muscle is more surface active than the salt-soluble fraction. The average equilibrium surface pressure at the air-liquid interface was 21.5 mN m(-1) for an aqueous extract and 20.1 mN m(-1) for a 1m KCl extract. The equilibrium surface pressure decreased from 21.7 mN m(-1) to 19.50mN m(-1) as the extraction time with Weber-Edsall solution increased from 15 min to 48 h. PMID- 22056102 TI - Odor thresholds of the C(19)-Delta(16)-steroids responsible for boar odor in pork. AB - Odor thresholds for each of the five C(19)-Delta(16)-steroids believed to contribute to boar odor in pork were determined using duo-trio test methodology. Threshold values for 5,16-androstadien-3beta-ol (I) and 4,16-androstadien-3-one (II) were approximately 10 MUg/g, whereas those for 5alpha-androst-16-en-3-one (III), 5alpha-androst-16-en-3alpha-ol (IV) and 5alpha-androst-16-en-3beta-ol (V) were about 1 MUg/g. Statistical comparisons of the mean threshold values for each of these compounds showed no difference (P < 0.05) among the mean thresholds of III, IV and V or between compounds I and II. The mean thresholds of compounds I and II were different (P < 0.05) from those of compounds III, IV and V. Triangle test methodology was employed to measure the ability of trained panelists to differentiate the odors of each of these five compounds either singly or in all combinations. Results showed that panelists were able to differentiate (P < 0.05) between the odors of the C(19)-Delta(16)-steroids possessing ketone groups (II and III) and those containing alcohol groups (I, IV and V). Panelists were not able, however, to differentiate (P < 0.05) between the odors of the three alcoholic steroids (I, IV and V), nor were they able to differentiate between the odors of the two ketonic steroids (II and III). PMID- 22056103 TI - Comparison of various types of starch when used in meat sausages. AB - Technological and sensory properties of meat sausages formulated with 4.0% of either potato flour, modified (acetylated distarch phosphate) potato starch, wheat, corn or tapioca starch were compared. Sausages were analyzed after cooking at temperatures between 65 and 85 degrees C followed by storage at 5 degrees C and -25 degrees C. Characteristics evaluated were weight loss during cooking and storage, instrumentally and sensory assessed firmness, taste and smell of sausages. The results revealed differences in the suitability of starches for use in meat sausages. Part of the differences could be ascribed to differences in gelatination properties of the starches. With the criteria used for evaluating quality, potato flour was rated as the best suited starch followed by wheat starch while tapioca was rated as the least suited. Corn starch required cooking temperatures above 75 degrees C and showed relatively low freeze/thaw stability. The modified potato starch stored well both above and below the freezing point. PMID- 22056104 TI - Ante-mortem detection of PSE and DFD by infrared thermography of pigs before stunning. AB - Using water-holding capacity and colour measurements (L and b values) as objective quality parameters, we have observed an increasing incidence of meat quality defects with the increasing skin surface temperature of pigs by infrared thermography prior to stunning. Below 32.2 degrees C, 50% of the 32 pigs measured had normal meat while the other half showed meat quality defects. Above 32.2 degrees C, however, 71% of the 49 pigs showed meat quality problems classified as moderate PSE (6%), PSE (30%), moderate DFD (22%) and DFD (37%). At this temperature level, meat quality of the remaining pigs was normal and decreased to 29%. Although infrared thermography of live animals cannot predict whether the meat will be PSE or DFD, it seems to be a practical and rapid method to detect pigs who will yield a significant proportion of meat quality defects. An early post-mortem identification of meat quality could supply the missing information. PMID- 22056105 TI - The effect of ageing treatment on the microbiology and storage characteristics of beef in modified atmosphere packs containing 25% CO(2) plus 75% O(2). AB - The influence of different ageing treatments (1 week hung in air; 1 and 3 weeks in vacuum packs) on the microbiological, colour, odour and rancidity characteristics of beef loin steaks during storage at 1 degrees and 6 degrees C in modified atmosphere packs (MA) containing 25% CO(2) + 75% O(2) was determined. Steaks from the 3-week ageing treatment discoloured more rapidly and developed off-odours sooner than those from the 1-week ageing treatments at both storage temperatures. Evidence of rancidity, using the thiobarbituric acid assay, was only observed in the 3-week aged steaks stored at 6 degrees C. The poorer storage stability of the 3-week aged steaks was explained by higher initial levels of bacteria resulting from growth during ageing. Leuconostocs were the dominant bacteria on most MA samples following storage and appeared the main cause of spoilage, although B. thermosphacta and Pseudomonas spp may have contributed to off-odours on samples aged hung and stored at 6 degrees C. PMID- 22056106 TI - The cumulative effect of nutritional, shearing and preslaughter washing stresses on the quality of lamb meat. AB - Carcass and meat characteristics were measured in lambs exposed to combinations of nutritional, shearing and preslaughter washing treatments. Both shearing and a low plane of nutrition reduced carcass weight (P < 0.001) and increased carcass leanness (P < 0.01). Tenderness and colour of M. longissimus dorsi were not significantly influenced by treatments even though there were substantial responses in meat pH. In lambs subjected to all three stressors pH was 0.40 units above control levels, significantly more than the sum of individual effects (P < 0.05), demonstrating a cumulative effect of stressors on meat pH. PMID- 22056107 TI - Microbiological characteristics of precooked, vacuum-packaged uncured beef and pork. AB - Microbiological examination of 29 packages of precooked, vacuum-packaged beef and pork products purchased at local and regional supermarkets along with 110 packages of precooked, vacuum-packaged, sliced roast beef obtained from a major meat processor did not disclose the presence of Escherichia coli, coagulase positive Staphylococcus aureus, Clostridium perfringens or Salmonella. The effects of storage temperature and length of storage on the microflora of 110 packages of sliced roast beef were determined at specific intervals of storage up to 84 days at 1 degrees and 5 degrees C, and up to 28 days at 10 degrees C. The microflora of samples stored at 1 degrees and 5 degrees C was dominated by Lactobacillus spp. when examined on day 28 and throughout the remainder of the 84 day test period. The microflora of samples held at 10 degrees C was dominated by Lactobacillus spp. until late in storage when Hafnia alvei became a major portion of the bacterial population. Precooked, sliced roast beef had a longer shelf life in laboratory controlled evaluations when stored at 1 degrees C as opposed to 5 degrees or 10 degrees C. PMID- 22056108 TI - A mass in the left flank. PMID- 22056109 TI - Diagnostic performance of initial salivary alpha-amylase activity for acute myocardial infarction in patients with acute chest pain. AB - BACKGROUND: To rule out acute myocardial infarction (AMI) in chest pain patients constitutes a diagnostic challenge to emergency department (ED) physicians. STUDY OBJECTIVES: To evaluate the diagnostic value of measuring salivary alpha-amylase (sAA) activity for detecting AMI in patients presenting to the ED with acute chest pain. METHODS: sAA activity was measured in a prospective cohort of 473 consecutive adult patients within 4 h of onset of chest pain. Comparisons were made between patients with a final diagnosis of AMI and those with non-AMI. Univariate analysis and multiple logistic regression model were used to identify independent clinical predictors of AMI. RESULTS: Initial sAA activity in the AMI group (n = 85; 266 +/- 127.6 U/mL) was significantly higher than in the non-AMI group (n = 388; 130 +/- 92.8 U/mL, p < 0.001). sAA activity levels were also significantly higher in patients with ST elevation AMI (n = 53) compared to in those with non-ST elevation AMI (n = 32) (300 +/- 141.1 vs. 210 +/- 74.1 U/mL, p < 0.001). The area under the receiver operating characteristic curve of sAA activity for predicting AMI in patients with acute chest pain was 0.826 (95% confidence interval [CI] 0.782-0.869), with diagnostic odds ratio 10.87 (95% CI 6.16-19.18). With a best cutoff value of 197.7 U/mL, the sAA activity revealed moderate sensitivity and specificity as an independent predictor of AMI (78.8% and 74.5%). CONCLUSIONS: High initial sAA activity is an independent predictor of AMI in patients presenting to the ED with chest pain. PMID- 22056110 TI - Provider perceptions concerning use of chest x-ray studies in adult blunt trauma assessments. AB - BACKGROUND: Although they infrequently lead to management changing diagnoses, chest x-rays (CXRs) are the most commonly ordered imaging study in blunt trauma evaluation. OBJECTIVES: To determine: 1) the reasons physicians order chest X-ray studies (CXRs) in blunt trauma assessments; 2) what injuries they expect CXRs to reveal; and 3) whether physicians can accurately predict low likelihood of injury on CXR. METHODS: At a Level I Trauma Center, we asked resident and attending physicians treating adult blunt trauma patients: 1) the primary reason(s) for getting CXRs; 2) what, if any, significant intrathoracic injuries (SITI) they expected CXRs to reveal; and 3) the likelihood of these injuries. An expert panel defined SITI as two or more rib fractures, sternal fracture, pulmonary contusion, pneumothorax, hemothorax, or aortic injury on official CXR readings. RESULTS: There were 484 patient encounters analyzed--65% of participating physicians were residents and 35% were attendings; 16 (3.3%) patients had SITI. The most common reasons for ordering CXRs were: "enough concern for significant injury" (62.9%) and belief that CXR is a "standard part of trauma work-up" (24.8%). Residents were more likely than attendings to cite "standard trauma work-up" (mean difference = 13.5%, p = 0.003). When physicians estimated a < 10% likelihood of SITI on CXR, 2.1% (95% confidence interval [CI] 1.0-4.1%) of patients had SITI; when they predicted a 10-25% likelihood, 5.7% (95% CI 1.2-15.7%) had SITI; and when they predicted a > 25% likelihood, 9.1% (95% CI 3.0-20.0%) had SITI. CONCLUSIONS: Physicians order CXRs in blunt trauma patients because they expect to find injuries and believe that CXRs are part of a "standard" work-up. Providers commonly do not expect CXRs to reveal SITI. When providers estimated low likelihood of SITI, the rate of SITI was very low. PMID- 22056111 TI - The medial-transverse approach for internal jugular vein cannulation: an example of lateral thinking. AB - BACKGROUND: Cannulation of the internal jugular vein (IJV) is traditionally performed using the central-longitudinal approach. Pneumothorax, carotid artery puncture, and failure to cannulate are uncommon, but by no means rare, complications. Ultrasound (US) guidance for IJV cannulation has reduced but not eliminated such complications. TECHNIQUE: We herein introduce a new approach, coined the "medial-transverse approach" due to the perpendicular angle at which the introducer needle is advanced toward the IJV from the median to lateral direction. DISCUSSION: The direction of the introducer needle is not toward the lung, thus virtually eliminating the possibility of pneumothorax. The image of the entire needle is seen when the US probe is typically orientated for a short axis view of the IJV and carotid artery, thus improving the chance of uncomplicated IJV puncture. We have used this technique with apparent success in thousands of cases over the past 20 years in two different institutions. CONCLUSION: A modified IJV cannulation technique that seems to have unique advantages over traditional approaches has been described. This technique is compatible with the blind and US-guided approaches. PMID- 22056112 TI - There is no doubt that the early identification of PKU and prompt and continuous intervention prevents mental retardation in most patients. PMID- 22056113 TI - Legislative solutions to unhealthy eating and obesity in Australia. AB - This paper discusses legislative interventions that have potential to address factors in the food environment that contribute to unhealthy eating patterns and increasing obesity rates in the Australian population, and political barriers to the implementation of these interventions. The paper devotes particular attention to legislative interventions to require disclosure of nutrition information about food and beverage products, which would help to inform consumer choices, and are, therefore, difficult to object to on personal responsibility or 'nanny state' grounds. It is suggested that these interventions seem to be gaining political acceptance in Australia, and may provide a starting point for incremental progress. PMID- 22056114 TI - Stem cells for GI motility disorders. AB - Currently available therapies for gastrointestinal motility conditions are often inadequate. Recent scientific advances, however, have facilitated the identification of neural stem cells as novel tools for cellular replenishment. Such cells can be generated from a number of tissue sources including the gut itself. Neural stem cells can readily be harvested from postnatal human gut including by conventional endoscopy, and in experimental transplantation studies appear capable of generating a neo-Enteric Nervous System. Current initiatives are addressing pre-clinical proof of concept studies in vivo utilising animal models of disease. Although definitive cell replenishment therapies for gut motility disorders appear to be an exciting and realistic prospect, even in the short-term, a number of challenges remain to be addressed before definitive clinical application. PMID- 22056115 TI - Conditioning of meat from different species. Relationship between tenderising and the levels of cathepsin B, cathepsin L, calpain I, calpain II and beta glucuronidase. AB - The conditioning times for beef, calf, lamb, pig and chicken M. pectoralis profundus were determined from extensibility measurements at 15 degrees C. Extracts from the same muscle from these animals and also rabbit were assayed for free and total cathepsin activities using a new method to determine the extent of inhibition by cystatins. A new method was also developed for the rapid estimation of each calpain. The results show that pig muscle contained most cathepsin activity. Cathepsin L appeared to be inhibited to a greater degree than cathepsin B in the pig, rabbit and chicken muscle extracts. These extracts also contained proportionately more cathepsin L than the other species. Chicken muscle contained only a low level of the more sensitive neutral proteinase, calpain I. It was concluded that the rapid conditioning time for chicken muscle could not be explained in terms of either the free or total levels of cathepsins B and L, nor of the individual calpain activities. PMID- 22056116 TI - Separation of vertebral epiphyses in bovine carcases. AB - Separation of vertebral epiphyses in the thoracolumbar region is a cause of rejection of beef carcases for Intervention storage. Incidence is highest in younger cattle and the problem is associated with certain types of hide puller and dressing technique. Three dressing methods are evaluated and tensile strenght of bone specimens is measured. PMID- 22056117 TI - Thermal transition of collagen in ovine connective tissues. AB - The thermal transition temperature (T(m)) of collagen in a range of muscle and non-muscle connective tissues from lambs, hoggets and mature sheep was measured by differential scanning calorimetry. The muscles selected were: semimembranosus (SM), semitendinosus (ST), biceps femoris (BF), Longissimus dorsi (LD) and psoas major (PM). Although the T(m) of intramuscular SM collagen from an aged ewe underwent no significant change with time post mortem, that of a 5-months-old lamb had dropped by 0.9 degrees C after 2 days at 19 degrees C. The epimysium of each muscle exhibited a higher T(m) than the corresponding intramuscular connective tissue. The LD and BF tendons each had a lower T(m) than corresponding intramuscular connective tissue but this was not true for the PM. Furthermore, the PM tendon generated an isometric tension more than five times that of the LD, BF or psoas minor tendons. This indicates that the PM tendon is richer in heatstable crosslinks than any of the other tendons investigated. In all tissues, except the liver capsule, there was an increase in T(m) with animal age. However, the rate of change T(m) varied from one tissue to another. For example, the SM intramuscular collagen matured at an earlier age than that of other muscles, the PM being slowest to mature. In keeping with the changes in T(m) values, the Warner-Bratzler peak force of ST muscles increased markedly in older sheep, but there was no significant difference in peak force of SM muscles between lambs, hoggets and mature sheep. PMID- 22056118 TI - Effect of feeding regimen, breed and sex condition on carcass composition and feed efficiency. AB - Eighty bulls and eighty steers representing four breed types (7/8 Angus. 7/8 Simmental, 7/8 Simmental * 7/8 Angus and 7/8 Simmental * 7/8 Hereford) were randomly assigned to two diets by sex class and breed type. Exotic breeds produced heavier, leaner, more muscular carcasses, with lower USDA quality grades and darker colored, coarser textured lean. Angus 9-10-11th rib composition showed that Angus tended to have less lean, more bone and the most fat when compared to the Simmental and Simmental crosses. Feeding the deferred diet resulted in carcasses with (P < 0.05) less fat, lower USDA quality grade, smaller ribeyes, more sensory panel detectable connective tissue, higher cooking losses and higher Instron shear values. Sex class caused differences (P < 0.05) in feed efficiency, carcass traits and sensory properties. PMID- 22056119 TI - Use of the Hennessy Grading Probe (GP) for predicting the meat, fat and bone yields of beef carcasses. AB - Left sides of 36 bulls, 22 cows, 57 steers and 38 heifer carcasses were weighed hot (HCWL) and were probed with the Hennessy Grading Probe (HGP) at five sites to give four subcutaneous fat depths, two M. longissimus dorsi depths and one total tissue depth measurement. A fat depth (GR) over the 10th rib was also measured by ruler probe. The left sides were later separated by knife into saleable eat (90% visual lean), fat trim and bone. Probe readings of subcutaneous fat thickness at the fatter rump sites (BF, 5-7 cm lateral to the perianal region over the M. biceps femoris; SC8, 8 cm lateral to the prominence of the sacral crest) were smaller than ruler measurements at the same sites. Probe eye muscle depth measurements were smaller than measurements taken at the same site by ruler. The BF measurement taken by probe, combined with HCWL, gave the best prediction of percentage fat trim (RSD = 2.0% for steers and 2.2% for heifers) and edible meat yield (RSD = 2.0% for steers and 2.6% for heifers) in the left sides of all the measurements studied, either singly or in combination. A major problem was to find a measurement site where subcutaneous fat was not removed from some carcasses during hide removal. PMID- 22056120 TI - The relationships between initial pH, reflectance and exudation in pig muscle. AB - Using data collected from several hundred pigs, the relationships of drip loss during storage, and reflectance, to pH(45) in the M. longissimus dorsi (LD) were both found to be biphasic. Muscles with a lower pH(45) lost more drip and were paler. Below pH 6.1, however, decreasing pH(45) had only a small effect on the weight of drip lost but a large influence on reflectance. In contrast, above pH 6.1, increasing pH(45) had a large influence on drip loss but only a small effect on reflectance. There was also a biphasic relationship between drip loss and reflectance with the discontinuity at 9.9% drip. Differences in pH(u) explained less than 15% of the variation in exudation and reflectance. PMID- 22056121 TI - Occurrence of giant fibers in muscles from wild pigs native to the United States. AB - The semimembranosus (SM) and triceps brachii (TB) muscles from wild pigs native to Florida. USA, were evaluated for histological characteristics. All three fiber types were present in both muscles in varying proportions, reflecting differences between tonic and phasic functioning muscles. Typical fiber arrangements were observed with red fibers grouped in clumps and surrounded by white fibers. The triceps brachii muscle contained a greater percentage of betaR and alphaR fibers and possessed more giant fibers than the SM muscle which contained more alphaW fibers. The giant fibers observed resembled betaR or alphaR fibers. The presence of hypertrophied fibers in the muscles from these wild pigs suggests that the 'giant fiber syndrome' is an intrinsic susceptibility for muscle fiber enlargement in these animals and not necessarily associated with breeding for muscularity since the carcasses from these pigs contained very small muscles and very little fat. PMID- 22056123 TI - Hospitalized patients with dementia: the dilemma of managing agitation. PMID- 22056124 TI - The interstitial location of selenium and arsenic in rocks associated with coal mining using ultrasound extractions and principal component analysis (PCA). AB - The release of selenium and arsenic from coal mine wastes into main waterways is an environmental cause for concern in the mining industry due to a myriad of subsequent ecotoxicological problems associated with the two metalloids. In a 2002 USEPA study undertaken in a mountaintop removal/valley fill (MTR/VF) mining area in southern West Virginia, measured Se concentrations were higher than the stipulated 5 ng/mL in 66 out of the 213 water samples collected. We studied the chemical composition of forty seven randomly selected pulverized core rock samples collected from depths of 25 ft to 881 ft from MTR/VF sites to determine the amounts of bioaccessible (ultrasound leachable) As and Se concentrations and their tentative locations within the rock matrix. The application of principal component analysis (PCA) to the chemical data, suggested that ultrasound leachable selenium concentrations were associated with 14 A d-spacing phyllosilicate clays (chlorite, montmorillonite and vermiculite all 2:1 layered clays) whilst ultrasound leachable arsenic concentrations were closely related to the concentration of illite, another 2:1 phyllosilicate clay. Negative correlations between leachable arsenic and selenium with kaolinite a 1:1 layered clay, were also observed. We used the observed negative correlations to rule out the presence of selenium or arsenic in 1:1 kaolinite. Hence mining waste from MTR/VF sites containing substantial amounts of illite and 14 A d-spacing clays may require to be placed in priority landfills or valley fills. PMID- 22056125 TI - Evaluation of some objective methods for measuring pork quality. AB - Several objective methods for estimating pork quality were evaluated, by correlating instrument values against visual scores by an experienced panel. The measurements examined were reflectance, fibre optic probe, pH, drip and Kapillarvolumeter values. Measurements were made on intact carcasses or after cutting across at the shoulder, mid-loin and ham. In chilled pork cuts, the fibre optic probe (FOP(u) value) and reflectometer agreed most closely with panel scores (r = 0.71 and 0.78, respectively). The probe has the added advantage of providing a useful indication of meat quality in the uncut carcass. Drip loss was about equally correlated with FOP(u), reflectance and Kapillarvolumeter values (r = 0.7 in all cases). In hot carcasses, the fibre optic probe (FOP(l) value) was superior to the pH(l) value for predicting panel score (r = 0.76 and -0.53 respectively) and reflectance (r = 0.80 and -0.60), whereas pH(l) was better than FOP(l) for predicting drip loss (r = -0.65 and 0.55). PMID- 22056126 TI - Post-mortem changes of connectin in chicken skeletal muscle. AB - To investigate the influence of connectin (titin) on meat tenderization during conditioning, changes in the content and the electrophoretic pattern of the connectin in chicken myofibrils isolated by gel permeation chromatography were studied. Significant difference of the content and the electrophoretic pattern of the connectin isolated was not observed between the preparations from fresh and stored muscle. Therefore, the connectin is unlikely to be responsible for the meat tenderization caused by conditioning. PMID- 22056127 TI - Glycogen depletion patterns in myofibres of cattle during stress. AB - The response of the three major types of fibre in beef M. longissimus dorsi during stress and recovery was examined with respect to cellular glycogen content. Two different forms of stress were induced in Friesian bulls, by mixing with strangers for a 5h period or by subcutaneous injections of adrenaline. Muscle biopsy samples were taken during stress and recovery for biochemical and histochemical analysis of glycogen content. Muscle glycogen concentration fell to 45% of the resting value during mixing stress and to 37% of the resting value after adrenaline treatment. Slow-twitch and fast-twitch fibre types responded differently to stress, and the differences were reversed in the two forms of stress studied. Mixing stress caused a greater loss of glycogen from the two fast fibre types than from the slow type while adrenaline caused a much greater loss of glycogen from the slow fibres than from the two fast fibre types. The results demonstrate that glycogen is selectively depleted in muscle fibres in response to stress and that the pattern of depletion is different in adrenaline versus mixing stress. PMID- 22056128 TI - Observations on the physiological effects of pithing cattle at slaughter. AB - Pithing cattle after captive bolt stunning, by thrusting a rod into the cranial cavity, causes violent muscular activity. The present observations have shown that this does not result in a rapid fall in the muscle pH similar to that occurring after electrical stimulation. The claim that pithing for a greater length than usual down the spinal cord causes marked enlargement of the spleen has not been substantiated. PMID- 22056129 TI - Metmyoglobin and inorganic metals as pro-oxidants in raw and cooked muscle systems. AB - The pro-oxidant activities of metmyoglobin (Mb) and metal ions on the induction of lipid oxidation in raw and heated water-washed muscle systems from fish, turkey, chicken, pork, beef and lamb and during storage of these systems at 4 degrees C, were investigated. Lipid oxidation was invariably faster in heated than in raw systems. In raw Mb-catalyzed systems, oxidation was slow over a 5-day period, except in fish, where significant (P < 0.05) increases in TBA values occurred; in contrast, significant (P < 0.05) increases in TBA values occurred in cooked fish, turkey, chicken and pork after 3 days of storage. Cooked beef and lamb, however, showed significant lipid oxidation only after 5 days of storage. Fe(2+) was found to be highly catalytic in cooked muscle. Cu(2+) and Co(2+) were less effective catalysts than Fe(2+); the overall pro-oxidant activity was in the order Fe(2+) > Cu(2+) > Co(2+) > Mb, and the susceptibility to lipid oxidation of the muscle systems was in the order: fish > turkey > chicken > pork > beef > lamb, probably reflecting the degree of unsaturation of the constituent triglyceride fractions. PMID- 22056130 TI - Trends in modern meat technology Edited by B. Krol, P. S. Van Roon and J. H. Houben, Pudoc, Centrex for Ag. Publ. & Documentation, Wageningen, The Netherlands, 125 pp., 1985. Price: Dfl. 50.00. PMID- 22056131 TI - Nodal/Activin signaling: a novel target for pancreatic cancer stem cell therapy. AB - Targeting of cancer stem cells (CSCs) has the potential to address the recalcitrance of pancreatic cancer to chemotherapy. In this issue of Cell Stem Cell, Lonardo et al. (2011) demonstrate that Nodal/Activin signaling is crucial for the maintenance and tumor-initiating capacity of pancreatic CSCs. PMID- 22056132 TI - Postnatal neurogenesis in the human forebrain: from two migratory streams to dribbles. AB - Subventricular zone neurogenesis occurs throughout life from rodents to primates, but the existence of a rostral migratory stream of immature neurons in postnatal human brains is controversial. A recent report in Nature (Sanai et al., 2011) identifies two neuronal migratory streams in infant human brains targeting the olfactory bulb and prefrontal cortex. PMID- 22056133 TI - Rewind to recover: dedifferentiation after cardiac injury. AB - In adult mammals, cardiomyocytes are known to reactivate an embryonic gene expression program after injury. In this issue of Cell Stem Cell, Kubin et al. (2011) show that oncostatin M regulates this dedifferentiation which, while beneficial for recovery from acute injury, if persistent results in heart failure in both rodents and humans. PMID- 22056134 TI - Guiding DNA methylation. AB - How DNA methyltransferases, with their limited target specificity, establish cell type-specific epigenetic patterns is poorly understood. Schubeler and colleagues (Lienert et al., 2011) now show that methylation-determining regions (MDRs) within promoter regions are sufficient to recapitulate endogenous patterns and dynamics of DNA methylation. PMID- 22056135 TI - You can count on this: barcoded hematopoietic stem cells. AB - Understanding how individual hematopoietic stem cells contribute to blood formation requires analysis at the single-cell level. Recently in Nature Biotechnology, Lu et al. (2011) tagged HSCs with unique molecular barcodes and used high-throughput sequencing to track their progeny after transplantation. PMID- 22056136 TI - Regulating autologous adult stem cells: the FDA steps up. AB - The Food and Drug Administration (FDA) has sought an injunction to prevent a US based company from offering an autologous adult stem cell treatment for musculoskeletal and spinal injuries. Given the alarming number of clinics promoting stem-cell-based interventions, the outcome of this case could have wide ranging implications. PMID- 22056137 TI - The impact of market volatility on the cell therapy industry. AB - Stock market volatility in the cell therapy industry has greatly hindered the investment necessary to fund translational therapies. Here, we review the volatility of leading companies and suggest that a distinct industry is maturing to a point at which the volatility should subside, providing a more attractive environment for future growth. PMID- 22056138 TI - Maintaining tissue homeostasis: dynamic control of somatic stem cell activity. AB - Long-term maintenance of tissue homeostasis relies on the accurate regulation of somatic stem cell activity. Somatic stem cells have to respond to tissue damage and proliferate according to tissue requirements while avoiding overproliferation. The regulatory mechanisms involved in these responses are now being unraveled in the intestinal epithelium of Drosophila, providing new insight into strategies and mechanisms of stem cell regulation in barrier epithelia. Here, we review these studies and highlight recent findings in vertebrate epithelia that indicate significant conservation of regenerative strategies between vertebrate and fly epithelia. PMID- 22056139 TI - Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling. AB - Cardiomyocyte remodeling, which includes partial dedifferentiation of cardiomyocytes, is a process that occurs during both acute and chronic disease processes. Here, we demonstrate that oncostatin M (OSM) is a major mediator of cardiomyocyte dedifferentiation and remodeling during acute myocardial infarction (MI) and in chronic dilated cardiomyopathy (DCM). Patients suffering from DCM show a strong and lasting increase of OSM expression and signaling. OSM treatment induces dedifferentiation of cardiomyocytes and upregulation of stem cell markers and improves cardiac function after MI. Conversely, inhibition of OSM signaling suppresses cardiomyocyte remodeling after MI and in a mouse model of DCM, resulting in deterioration of heart function after MI but improvement of cardiac performance in DCM. We postulate that dedifferentiation of cardiomyocytes initially protects stressed hearts but fails to support cardiac structure and function upon continued activation. Manipulation of OSM signaling provides a means to control the differentiation state of cardiomyocytes and cellular plasticity. PMID- 22056140 TI - Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. AB - Nodal and Activin belong to the TGF-beta superfamily and are important regulators of embryonic stem cell fate. Here we investigated whether Nodal and Activin regulate self-renewal of pancreatic cancer stem cells. Nodal and Activin were hardly detectable in more differentiated pancreatic cancer cells, while cancer stem cells and stroma-derived pancreatic stellate cells markedly overexpressed Nodal and Activin, but not TGF-beta. Knockdown or pharmacological inhibition of the Nodal/Activin receptor Alk4/7 in cancer stem cells virtually abrogated their self-renewal capacity and in vivo tumorigenicity, and reversed the resistance of orthotopically engrafted cancer stem cells to gemcitabine. However, engrafted primary human pancreatic cancer tissue with a substantial stroma showed no response due to limited drug delivery. The addition of a stroma-targeting hedgehog pathway inhibitor enhanced delivery of the Nodal/Activin inhibitor and translated into long-term, progression-free survival. Therefore, inhibition of the Alk4/7 pathway, if combined with hedgehog pathway inhibition and gemcitabine, provides a therapeutic strategy for targeting cancer stem cells. PMID- 22056141 TI - Sustained activation of mTOR pathway in embryonic neural stem cells leads to development of tuberous sclerosis complex-associated lesions. AB - Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder characterized by hamartomatous neurological lesions that exhibit abnormal cell proliferation and differentiation. Hyperactivation of mTOR pathway by mutations in either the Tsc1 or Tsc2 gene underlies TSC pathogenesis, but involvement of specific neural cell populations in the formation of TSC-associated neurological lesions remains unclear. We deleted Tsc1 in Emx1-expressing embryonic telencephalic neural stem cells (NSCs) and found that mutant mice faithfully recapitulated TSC neuropathological lesions, such as cortical lamination defects and subependymal nodules (SENs). These alterations were caused by enhanced generation of SVZ neural progeny, followed by their premature differentiation and impaired maturation during both embryonic and postnatal development. Notably, mTORC1 dependent Akt inhibition and STAT3 activation were involved in the reduced self renewal and earlier neuronal and astroglial differentiation of mutant NSCs. Thus, finely tuned mTOR activation in embryonic NSCs may be critical to prevent development of TSC-associated brain lesions. PMID- 22056142 TI - Rac mediates mouse spermatogonial stem cell homing to germline niches by regulating transmigration through the blood-testis barrier. AB - The homing ability of spermatogonial stem cells (SSCs) allows them to migrate into niches after being transplantated into infertile testes. Transplanted SSCs attach to Sertoli cells and transmigrate through the blood-testis barrier (BTB), formed by inter-Sertoli tight junctions, toward niches on the basement membrane. The most critical step is the passage through the BTB, which limits the homing efficiency to <10%. Here we demonstrated the involvement of Rac1 in SSC transmigration. Rac1-deficient SSCs did not colonize the adult testes, but they reinitiated spermatogenesis when transplanted into pup testes without a BTB. Moreover, a dominant-negative Rac1 construct not only reduced the expression of several claudin proteins, which comprise the BTB, but also increased SSC proliferation both in vitro and in vivo. Short hairpin RNA (shRNA) -mediated suppression of claudin3, which was downregulated by Rac inhibition, reduced the SSC homing efficiency. Thus, Rac1 is a critical regulator of SSC homing and proliferation. PMID- 22056143 TI - Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients. AB - Gene signatures derived from cancer stem cells (CSCs) predict tumor recurrence for many forms of cancer. Here, we derived a gene signature for colorectal CSCs defined by high Wnt signaling activity, which in agreement with previous observations predicts poor prognosis. Surprisingly, however, we found that elevated expression of Wnt targets was actually associated with good prognosis, while patient tumors with low expression of Wnt target genes segregated with immature stem cell signatures. We discovered that several Wnt target genes, including ASCL2 and LGR5, become silenced by CpG island methylation during progression of tumorigenesis, and that their re-expression was associated with reduced tumor growth. Taken together, our data show that promoter methylation of Wnt target genes is a strong predictor for recurrence of colorectal cancer, and suggest that CSC gene signatures, rather than reflecting CSC numbers, may reflect differentiation status of the malignant tissue. PMID- 22056144 TI - Diversity and toxigenicity among members of the Bacillus cereus group. AB - Members of the Bacillus cereus group were isolated from rice products by centrifugation-plating and conventional spread-plating methods. Random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) results showed broad diversity among the strains and revealed some associations among isolates from raw and cooked rice samples, at the genotypic level. A comparatively greater diversity among strains was observed in isolates from raw rice than those from cooked rice and, generally, the RAPD profiles of isolates from raw and cooked rice were different, with only a few of them common to both types of rice. The toxigenic potential of the isolates was also determined by molecular and immunoassay analyses. The results revealed that most isolates from the B. cereus group were potentially or actually toxigenic, and some isolates could produce both diarrhoeal and emetic toxins. Generally, isolates belonging to the B. cereus group with the same RAPD pattern were shown to have a similar profile of enterotoxigenicity. PMID- 22056145 TI - Biodiversity of Saccharomyces cerevisiae populations in Malbec vineyards from the "Zona Alta del Rio Mendoza" region in Argentina. AB - The "Zona Alta del Rio Mendoza" (ZARM) is the major Malbec grape viticulture region of Argentina. The aim of the present study was to explore Saccharomyces cerevisiae biodiversity in ZARM vineyards. Interdelta PCR and RFLP mtDNA molecular markers were applied to differentiate S. cerevisiae strains. The presence of commercial strains on ZARM vineyards was also assessed. Our results reveal a highly diverse, but genetically closely related, S. cerevisiae population (containing more than 190 molecular patterns among 590 S. cerevisiae isolates). According to the S. cerevisiae strain diversity found in vineyards, they were classified as vineyards with high and low polymorphic S. cerevisiae populations. Six vineyards showed a high polymorphic population, with more than 20 different S. cerevisiae molecular patterns. S. cerevisiae populations in these vineyards were diverse and irregularly distributed, with different strains in each vineyard site. Low polymorphic S. cerevisiae population vineyards displayed very low yeast diversity, with only 9 to 10 different S. cerevisiae strains and presence of two commercial strains widely distributed. Population diversity estimators were calculated to determine the population structure of S. cerevisiae in the ZARM vineyards. The obtained values support the hypothesis that the eight sampled subpopulations come indeed from a larger population. PMID- 22056146 TI - Development, implementation and initial evaluation of narrative virtual patients for use in vocational mental health nurse training. AB - Simulation techniques such as virtual patients (VPs) are valuable tools for teaching and learning a range of clinical proficiencies. Compared with other forms of simulation, however, the reported use of VPs within nursing is limited. Descriptions of simple, low cost methods for the development of VP devices could help facilitate their wider implementation and use in nursing education and training. In order to encourage broader use of VP technologies within nursing, this paper aims to expand current knowledge of VP creation by reference to the development of two virtual mental health patients produced for a multilingual e learning course for European mental health nurses. Focusing on narrative VPs, the paper provides a brief overview of various types and potential uses of VP techniques, along with central elements of good practice in VP development. The five phase development framework used in the creation of the two VPs is presented. Processes detailed include the design and construction of case scenarios and multimedia components, in addition to initial usability and validity testing. VPs like those described here are a relatively inexpensive way of integrating virtual simulation technology into nursing education, particularly within online, blended and/or cross-cultural learning environments. PMID- 22056147 TI - Small molecules induce efficient differentiation into insulin-producing cells from human induced pluripotent stem cells. AB - Human induced pluripotent stem (hiPS) cells have potential uses for drug discovery and cell therapy, including generation of pancreatic beta-cells for diabetes research and treatment. In this study, we developed a simple protocol for generating insulin-producing cells from hiPS cells. Treatment with activin A and a GSK3beta inhibitor enhanced efficient endodermal differentiation, and then combined treatment with retinoic acid, a bone morphogenic protein inhibitor, and a transforming growth factor-beta (TGF-beta) inhibitor induced efficient differentiation of pancreatic progenitor cells from definitive endoderm. Expression of the pancreatic progenitor markers PDX1 and NGN3 was significantly increased at this step and most cells were positive for anti-PDX1 antibody. Moreover, several compounds, including forskolin, dexamethasone, and a TGF-beta inhibitor, were found to induce the differentiation of insulin-producing cells from pancreatic progenitor cells. By combined treatment with these compounds, more than 10% of the cells became insulin positive. The differentiated cells secreted human c-peptide in response to various insulin secretagogues. In addition, all five hiPS cell lines that we examined showed efficient differentiation into insulin-producing cells with this protocol. PMID- 22056148 TI - Results of a pilot program to improve phosphorus outcomes in hemodialysis patients. AB - OBJECTIVE: End-stage renal disease causes dysregulation of bone and mineral metabolism, including increased serum phosphorus levels. Kidney Foundation Kidney Disease Outcome Quality Initiative 2003 guidelines recommend maintaining phosphorus levels between 3.5 and 5.5 mg/dL in dialysis patients. We examined the effects of a focused phosphorus management pilot program designed to improve the percentage of hemodialysis patients achieving phosphorus levels <5.5 mg/dL. DESIGN, SETTING, SUBJECTS, AND INTERVENTION: We conducted a prospective, multicenter, single-arm study at 8 geographically diverse at-risk facilities (n = 702 hemodialysis patients) in a large U.S. dialysis organization. The focused phosphorus management program provided in-service training to staff members, and provided patients with diet and phosphorus management through in-center, 1:1 education and support, direct-to-patient adherence communications, benefit management assistance, and adherence support specific to lanthanum carbonate over a 6-month period. MAIN OUTCOME MEASURE: Facility-level markers of bone and mineral metabolism (phosphorus, parathyroid hormone, corrected calcium) and nutritional status (serum albumin, normalized protein catabolic rate) were assessed before and after program implementation. RESULTS: There was a significant increase in the percentage of patients per facility achieving phosphorus levels <5.5 mg/dL (mean +/- SD at baseline = 61.6% +/- 5.2%; month 6 = 71.3% +/- 9.0%; P < .01) and parathyroid hormone (150 to 300 pg/mL; mean +/- SD at baseline = 39.1% +/- 2.4%; month 6 = 44.5% +/- 7.0%; P = .04). During the course of the evaluation, mean calcium, albumin, and normalized protein catabolic rate levels did not change significantly. CONCLUSIONS: These results show proof of-concept that a focused phosphorus management program targeting both staff members and patients can significantly improve patient outcomes without compromising nutritional status. PMID- 22056149 TI - Comparison of markers of appetite and inflammation between hemodialysis patients with and without failed renal transplants. AB - OBJECTIVE: The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aim to compare the markers of appetite and malnutrition, and their relation with inflammation in HD patients with and without previous kidney transplantation. METHODS: Fifty-six patients with failed renal allografts at least 3 months on dialysis (31 men, 25 women; mean age, 46 +/- 9 years) and 77 HD patients who never underwent a transplant (43 men, 34 women; mean age, 50 +/- 15 years) were included in the study. The appetite and diet assessment tool (ADAT) was used to determine the self reported appetite of patients. Serum concentrations of ghrelin, leptin, insulin like growth factor 1 (IGF-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and high-sensitivity C-reactive protein (hs-CRP) were measured. Associations among these variables were analyzed. RESULTS: There were no significant differences considering age, gender or duration of renal replacement therapy between the 2 groups. The scores from Appetite and Diet Assessment Tool were significantly higher in the failed transplant group. Serum ghrelin levels were significantly higher and serum albumin levels were significantly lower in the failed-transplant group. Serum leptin levels were similar between 2 groups. In addition, hs-CRP, IL-6, and TNF alpha levels, which were used as inflammatory parameters, were significantly higher in the failed-transplant group. CONCLUSIONS: Elevated serum ghrelin levels and inflammation may cause diminished appetite and malnutrition in patients with failed renal allografts, and higher levels of this hormone seem to be associated with inflammation caused by retained failed allografts. PMID- 22056150 TI - Adductor pollicis muscle thickness: a promising anthropometric parameter for patients with chronic renal failure. AB - INTRODUCTION: Protein-calorie malnutrition is a prevalent disorder in chronic renal failure (CRF) and a major risk factor for increased mortality in hemodialysis (HD) patients. Although many methods have been used to assess malnutrition in CRF, the role of adductor pollicis muscle thickness (APMt) is not established yet. AIMS: This study aimed to analyze the APMt in HD patients and to investigate the correlation between APMt and conventional anthropometric, laboratory, and bioelectrical impedance markers, as well as its association with mortality/morbidity in a period of 12 months of follow-up. SUBJECTS AND METHODS: The study included 143 HD patients from a single facility. After dialysis, the dry weight, height, mid-arm circumference, triceps skinfold thickness, and APMt were measured. Subsequently, the body mass index, percentage of standard body weight, the mid-arm muscle circumference, and the mid-arm muscle area were calculated. Blood counts were performed for hemoglobin, creatinine, and albumin. Patients were also submitted to a single-frequency tetrapolar bioimpedance test for measuring resistance, reactance, phase angle, and percentage of body cell mass. The correlation between APMt and anthropometric, laboratory, and bioelectrical impedance parameters was calculated using Pearson's linear correlation. Multiple linear regression analysis was used to select independent risk factors to death and hospitalizations in 6 and 12 months of follow-up, among parameters selected by univariate analysis. RESULTS: Patients were aged 52.2 +/- 16.6 years (20 to 83 years) on average, 58% were men, and mean dialysis vintage was 5.27 +/- 5.12 years. APMt was 11.85 +/- 1.63 mm (men, 12.34 +/- 1.53; women, 11.19 +/- 1.51; P < .0001). APMt was positively correlated with body mass index (r = 0.37; P < .0001), mid-arm circumference (r = 0.437; P < .0001), mid-arm muscle circumference (r = 0.494; P < .0001), mid-arm muscle area (r = 0.449; P < .0001), percentage of standard body weight (r = 0.355; P = .000), creatinine (r = 0.230; P = .006), albumin (r = 0.207; P = .013), percentage of body cell mass (r = 0.293; P = .000), and phase angle (r = 0.402; P < .0001), and negatively correlated with resistance (r = -0.403; P < .0001). The APMt <=10.6 mm was associated with a 3.3 times greater risk of hospitalization within 6 months of follow-up (OR = 3.3, 95% CI: 1.13 to 9.66; P = .029) compared with patients with an APMt >10.6 mm. The APMt was not associated with risk of death at 6 and 12 months or hospitalization within 12 months of follow-up. CONCLUSION: This is the first study testing APMt as an anthropometric marker in HD patients. The parameter is easy to measure and does not seem to be significantly affected by variations in hydration status. The parameter was significantly correlated with markers reflecting the condition of the muscle compartment, but not with parameters estimating the fat mass. The determination of an APMt cutoff point for malnutrition in patients with CRF and its correlation with morbidity and mortality will require further investigation in clinical studies. PMID- 22056151 TI - Is nutritional status associated with self-reported sleep quality in the HEMO study cohort? AB - OBJECTIVES: To explore the relationship between sleep quality and common measures of nutritional status in the Hemodialysis (HEMO) Study cohort. To investigate sleep quality scores based on longitudinal changes in measures of nutritional status, adjusting for case mix, lifestyle, and comorbidity factors. DESIGN: Secondary analysis of the HEMO Study data. SETTING: A 7-year, prospective, multicenter, randomized clinical trial in maintenance hemodialysis patients. PATIENTS: Eighteen hundred forty-six patients aged between 18 and 80 years were randomized; 1,803 (97.7%) completed the Kidney Disease Quality of Life Long Form (KDQOL-LF) at baseline. Mean age was 58 years, 44% were male, 64% were Black, 37% had diabetes, and 32% had hypertension; mean duration of dialysis was 3.8 years. MAIN OUTCOME MEASURES: The univariate and multivariate relationships of measures of nutritional status (i.e., serum albumin, serum creatinine, postdialysis weight, body mass index, dietary protein and energy intake, and assessment of appetite) and sleep quality assessed using the sleep subscale from the KDQOL-LF. RESULTS: In univariate analysis, sleep quality score decreased significantly in a linear fashion as appetite rating decreased from very good to very poor on both dialysis days (63.6 +/- 21.8 to 43.6 +/- 22.9, P < .0001) and nondialysis days (63.2 +/- 21.6 to 40.7 +/- 25.7, P < .0001), with higher scores reflecting better sleep quality. In multivariable analysis, serum creatinine was the only laboratory variable that was significantly associated with sleep quality score (beta = 0.49, P = .0004). Poorer appetite on both dialysis days (beta = -1.5, P < .0001) and nondialysis days (beta = -1.7, P < .0001) was associated with poor sleep quality. CONCLUSIONS: Self-reported sleep quality was associated with appetite and serum creatinine. A simple questionnaire to assess sleep disorders in dialysis patients should be administered routinely to detect those patients at risk of sleep complaints. However, further studies are needed to determine whether improving sleep quality, directly or indirectly, would improve morbidity and mortality. PMID- 22056153 TI - Stephen Lawrie: PsySTAR trek, the next generation. PMID- 22056154 TI - High-risk prostate cancer: treat the prostate. PMID- 22056152 TI - Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. AB - BACKGROUND: Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. METHODS: Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65-69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. RESULTS: Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6.0 years (IQR 4.4-8.0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70-78 vs 66%, 60-70; hazard ratio [HR] 0.77, 95% CI 0.61-0.98, p=0.033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0.5%) in the ADT only group, two (0.3%) in the ADT and RT group; diarrhoea grade >3, four patients (0.7%) vs eight (1.3%); urinary toxicity grade >3, 14 patients (2.3%) in both groups). INTERPRETATION: The benefits of combined modality treatment--ADT and RT--should be discussed with all patients with locally advanced prostate cancer. FUNDING: Canadian Cancer Society Research Institute, US National Cancer Institute, and UK Medical Research Council. PMID- 22056155 TI - Autoimmune diseases have been the focus of intense research efforts. PMID- 22056156 TI - Traumatic brain injury: prognostic implications of cortical electrical disturbances. PMID- 22056157 TI - Spreading depolarisations and outcome after traumatic brain injury: a prospective observational study. AB - BACKGROUND: Pathological waves of spreading mass neuronal depolarisation arise repeatedly in injured, but potentially salvageable, grey matter in 50-60% of patients after traumatic brain injury (TBI). We aimed to ascertain whether spreading depolarisations are independently associated with unfavourable neurological outcome. METHODS: We did a prospective, observational, multicentre study at seven neurological centres. We enrolled 109 adults who needed neurosurgery for acute TBI. Spreading depolarisations were monitored by electrocorticography during intensive care and were classified as cortical spreading depression (CSD) if they took place in spontaneously active cortex or as isoelectric spreading depolarisation (ISD) if they took place in isoelectric cortex. Investigators who treated patients and assessed outcome were masked to electrocorticographic results. Scores on the extended Glasgow outcome scale at 6 months were fitted to a multivariate model by ordinal regression. Prognostic score (based on variables at admission, as validated by the IMPACT studies) and spreading depolarisation category (none, CSD only, or at least one ISD) were assessed as outcome predictors. FINDINGS: Six individuals were excluded because of poor-quality electrocorticography. A total of 1328 spreading depolarisations arose in 58 (56%) patients. In 38 participants, all spreading depolarisations were classified as CSD; 20 patients had at least one ISD. By multivariate analysis, both prognostic score (p=0.0009) and spreading depolarisation category (p=0.0008) were significant predictors of neurological outcome. CSD and ISD were associated with an increased risk of unfavourable outcome (common odds ratios 1.56 [95% CI 0.72-3.37] and 7.58 [2.64-21.8], respectively). Addition of depolarisation category to the regression model increased the proportion of variance in outcome that could be attributed to predictors from 9% to 22%, compared with the prognostic score alone. INTERPRETATION: Spreading depolarisations were associated with unfavourable outcome, after controlling for conventional prognostic variables. The possibility that spreading depolarisations have adverse effects on the traumatically injured brain, and therefore might be a target in the treatment of TBI, deserves further research. FUNDING: US Army CDMRP PH/TBI research programme. PMID- 22056158 TI - A microbiological survey of fresh meat in the supermarket trade. Part 1: Carcasses and contact surfaces. AB - Sanitary conditions were monitored at eleven supermarkets (from two major chains, Sup groups A & B) in the South African butcher industry. The variables measured were the temperature of carcasses and environments, the muscle pH of carcasses and the microbiological status of carcasses and human or personal and equipment contact surfaces (chillers-three surfaces, delivery trucks-five surfaces, cutting rooms-16 surfaces). All supermarkets, except one, received beef carcasses, distributed by one of two wholesale organizations from the same abattoir. No consistency was found in the contamination level of different parts of carcasses at different supermarkets, although there was a tendency for fore quarters to be more contaminated than hind quarters. Chiller surfaces, delivery truck surfaces and equipment had significantly different microbial counts at the different supermarkets. Sup group B received carcasses with higher mean surface temperatures and microbial counts than those of the carcasses received by Sup group A, but the mean microbial count of equipment was lower than that encountered at Sup group A. The result was less contaminated meat at the supermarkets in Sup group B, illustrating how a combination of the microbial quality of carcasses received by such supermarkets, and the sanitary programme in operation at such supermarkets affects the contamination level of retail premises. It could furthermore be shown that personnel surfaces (hands and clothes) and equipment like saws and mincers are consistent contributors to contamination at the retail level of the meat industry. PMID- 22056159 TI - A microbiological survey of fresh meat in the supermarket trade. Part 2: beef retail cuts. AB - An assessment was made of the microbiological quality of the final product (different retail cuts), produced by two different retail supermarket groups (A & B). The influence of sanitary conditions on the microbiological quality of the final product was evaluated, and the possible influences on shelf life were determined. Supermarket group A (Sup group A) received carcasses with significantly lower surface counts of micro-organisms than supermarket group B (Sup group B), while the latter had a more efficient overall sanitation programme than supermarket group A. Five cuts were monitored for the presence of total aerobic counts, psychrotrophic counts, lactobacilli, Enterobacteriaceae and numbers of Pseudomonadaceae present. A shelf life study was also executed by repeating these enumerations on the same meat samples after refrigerated storage at 5 degrees C for 2 and 4 days, respectively. It is generally accepted that a good refrigeration or chilling regime will preserve the inherent meat quality, but in this study it was found that neither served as a guarantee of quality. The more stringent hygiene at retail level of Sup group B yielded consistently lower mean counts of the different bacterial groups for all the meat cuts monitored and, thus meat with an extended shelf life. The total count (at 30 degrees C) on meat cuts was the highest, followed by the psychrotrophs, the Pseudomonadaceae the Enterobacteriaeae and the lactobacilli. Minced meat generally had the highest mean aerobic total microbial counts. This count on minced meat might be a suitable indicator for monitoring the overall sanitary condition of a retail premises. The results re-emphasized the multi-factorial complexity of fresh meat quality and shelf life. The microbial quality of the raw material (carcasses), the maintenance of the cold chain, sanitary condition of premises, equipment and personnel surfaces and general management practices are factors that collectively determine the microbiological quality of the product. PMID- 22056160 TI - The effect of electrical stimulation, time of boning and high temperature conditioning on sensory quality traits of porcine Longissimus dorsi muscle. AB - The effects of electrical stimulation (300 V, 1 A, 50 Hz, AC, 30 s) and high temperature conditioning (4h/15 degrees C) on sensory quality traits of hot- and cold-boned, vacuum-packaged longissimus dorsi muscle of halothanenegative pigs were assessed at 12 days post mortem. Electrical stimulation accelerated the pH fall significantly, but had negligible effects on all quality traits measured, i.e. shear force, drip formation, fresh meat colour, cooking loss and degree of sarcoplasmic protein denaturation (p > 0.05). As compared with cold boning, hot boning significantly lowered drip losses (p < 0.05). Shear forces, which increased as a result of hot boning (p < 0.05), were reduced again through a 4 h/15 degrees C conditioning period before chilling at 1 +/-1 degrees C. In addition, high temperature conditioning resulted in significantly lower drip losses (p < 0.05). It is suggested that prevention of cold-induced reduction of proteolytic enzyme activity is primarily responsible for both these findings. PMID- 22056161 TI - Antagonistic effect of some starter cultures on enterobacteriaceae (E. coli). AB - The ability of Lactobacillus jensenii and Streptococcus 17SB to inbhibit Escherichia coli was demonstrated. The practical application of the inhibition was examined. Possible roles for several factors in the mechanism of inhibition by Lactobacillus jensenii and Streptococcus 17SB are briefly discussed. The effects of pH reached and acids produced by starters on the growth of Escherichia coli are described. PMID- 22056162 TI - Effects of early post-mortem ageing on intramuscular collagen stability, yield and composition. AB - Post-mortem changes in the composition and physical stability of bovine intramuscular collagen were evaluated during a 24 h ageing period. The yield of intramuscular connective tissue (IMCT) isolated from the infraspinatus muscle samples and the carbohydrate content of that material did not change significantly (P > 0.05) during the ageing period. The collagen content and total protein content of the isolated IMCT increased (P < 0.05) through 8 h post mortem. Moisture content of the isolated material decreased numerically but not significantly (P > 0.05). Collagen thermal shrinkage temperature (T(s)) decreased (P < 0.01) and collagen solubility increased (P < 0.05) during the ageing period with most of the changes occurring in the first 8 h. PMID- 22056163 TI - Effect of sodium chloride concentration on pH, water-holding capacity and extractable protein of prerigor and postrigor ground beef. AB - Fifteen beef cattle of similar age and management history were randomly allotted by slaughter days into three groups. Paired sternomandibularis were removed immediately following bleeding and trimmed of visible fat and connective tissue. They were randomly labelled as prerigor and postrigor and assigned to a 0, 0.5, 1.0, 2.0 or 4.0% NcCl treatment. Water-holding capacity (WHC), pH, the ratio of absorbance at 250 nm over the absorbance at 260 nm (R-values), and 1.0m NaCl extractable protein (EP) were monitored over treatment times. The 0 h samples were defined as when the NaCl was incorporated with the muscle. R-values verified that 0 h samples were in the prerigor or postrigor state. Ultimate pH remained higher (P < 0.05) in prerigor homogenates with increasing NaCl concentration. EP and WHC were higher (P < 0.05) in prerigor than in postrigor homogenates with 2 and 4% NaCl at all time periods. Prerigor homogenates containing 0.5 and 1.0% NaCl had higher (P < 0.05) WHC at 12, 24, 24, 48 and 96h than similarly treated postrigor homogenates and as high or higher WHC than any postrigor treatment. Results of this study indicate an advantage to using low NaCl concentrations in prerigor salted beef. PMID- 22056164 TI - Colour stability of minced beef. Ultraviolet barrier in packaging material reduces light-induced discoloration of frozen products during display. AB - The colour stability of minced beef, as measured by tristimulus colorimetry during freezer storage in a display cabinet illuminated with fluorescent tubes (product temperature -18 degrees C), was found to be significantly improved by an ultraviolet-light barrier in the packaging material. In general, a positive effect on colour stability of beef with barriers excluding light below 350 nm is to be expected at storage temperatures up to approximately 5 degrees C. This prediction is based on calculations using the energy of activation for the thermal autoxidation of oxymyoglobin and the quantum yield at different wavelengths for the competitive photochemical autoxidation process. PMID- 22056165 TI - Multi-stage versus single-stage inflation and deflation cycle for alternating low pressure air mattresses to prevent pressure ulcers in hospitalised patients: a randomised-controlled clinical trial. AB - INTRODUCTION: The duration and the amount of pressure and shear must be reduced in order to minimize the risk of pressure ulcer development. Alternating low pressure air mattresses with multi-stage inflation and deflation cycle of the air cells have been developed to relieve pressure by sequentially inflating and deflating the air cells. Evidence about the effectiveness of this type of mattress in clinical practice is lacking. AIM: This study aimed to compare the effectiveness of an alternating low pressure air mattress that has a standard single-stage inflation and deflation cycle of the air cells with an alternating low pressure air mattress with multi-stage inflation and deflation cycle of the air cells. METHODS AND MATERIALS: A randomised controlled trial was performed in a convenience sample of 25 wards in five hospitals in Belgium. In total, 610 patients were included and randomly assigned to the experimental group (n=298) or the control group (n=312). In the experimental group, patients were allocated to an alternating low pressure air mattress with multi-stage inflation and deflation cycle of the air cells. In the control group, patients were allocated to an alternating low pressure air mattress with a standard single-stage inflation and deflation cycle of the air cells. The outcome was defined as cumulative pressure ulcer incidence (Grade II-IV). An intention-to-treat analysis was performed. RESULTS: There was no significant difference in cumulative pressure ulcer incidence (Grade II-IV) between both groups (Exp.=5.7%, Contr.=5.8%, p=0.97). When patients developed a pressure ulcer, the median time was 5.0 days in the experimental group (IQR=3.0-8.5) and 8.0 days in the control group (IQR=3.0-8.5) (Mann-Whitney U-test=113, p=0.182). The probability to remain pressure ulcer free during the observation period in this trial did not differ significantly between the experimental group and the control group (log-rank chi(2)=0.013, df=1, p=0.911). CONCLUSION: An alternating low pressure air mattress with multi-stage inflation and deflation of the air cells does not result in a significantly lower pressure ulcer incidence compared to an alternating low pressure air mattress with a standard single-stage inflation and deflation cycle of the air cells. Both alternating mattress types are equally effective to prevent pressure ulcer development. PMID- 22056166 TI - Post-mortem processing of export beef in Costa Rica. AB - Eighteen intact male beef animals of 2 1 2 to 3 years of age, weighing 400-425 kg and fed entirely on rangelands grass, were slaughtered in a Costa Rican export plant. Six animals each were assigned to: low-voltage stimulation (75V), high voltage stimulation (350V) and control. Hot-boning coupled with various chilling rates was also investigated. Mean muscle pH values for all treatment groups were above 6.4 at 1 1 2 h after slaughter, which may be related to the fact the animals were intact males which had been exposed to stressful conditions prior to slaughter. Palatability traits measured were tenderness, juiciness, flavor and overall desirability. With the exception of tenderness, there were no significant differences among electrical stimulation or chill treatments, and there were no interactions. The low-voltage electrical-stimulation treatment produced less tender meat (P<0.05) than the high-voltage treatment, but there was no significant difference compared to the control. In an attempt to explain the finding that electrical stimulation had little or no effect on tenderness, the data were inspected in regard to ultimate pH. The panel score for samples with an ultimate pH less than 6 was 3.27, and for samples with a pH higher than 6 it was 5.70. A possible explanation is to suggest that the high-pH group underwent appreciable neutral proteolytic enzyme activity compared to the low-pH group. PMID- 22056167 TI - Effect of temperature of comminution on the stability and eating quality of 'English' sausages. AB - Sausages were prepared after equilibrating the ingredients to temperatures in the range 2 degrees to 37 degrees C. Following comminution for 6.5 min the temperatures of the batters ranged from 15 to 33 degrees C and their pHs from 6.25 to 6.48. During storage at -20 degrees C sausages prepared from the high temperature batters lost more weight than those made from batters prepared at the lower temperatures (0.3% compared to 1.2%). Increasing temperature of comminution led to increased cooking losses, softening in texture and darkening in colour. However, even at the highest temperatures complete emulsion breakdown did not occur as cooling losses were still only about 20%. Subjective assessment indicated that at least up to comminution temperatures of 25 degrees C the sausages were acceptable. At temperatures above 30 degrees C off-flavours developed. It is suggested that comminuted meat products can be manufactured in situations where refrigeration is not available, provided a preservation system can be devised to inhibit microbial and chemical spoilage. PMID- 22056168 TI - Immediate effects of ionizing radiation on the structure of unfrozen bovine muscle tissue. AB - To measure the immediate changes in the ultrastrcucture of meat induced by ionizing radiation, bovine longissimus dorsi muscle was irradiated with (137) Cs 72 h after slaughter. The temperature of the samples during irradiation was maintained between 0 and 4 degrees C to avoid cellular changes caused by freeze/thaw. Muscle was irradiated at 5, 10, 30 and 50 kGy. At low levels (up to 10 kGy) of radiation, changes in muscle structure were minimal. At levels above 30 kGy major increases in myofibril fragmentation and decreases in the tensile strength of raw and cooked muscles were noted. SDS gel electrophoresis indicated a decrease in myosin. No changes in the ultrastructure were observed using transmission electron microscopy. PMID- 22056169 TI - A comparison of the agar gel immuno-diffusion (AGID) and counter immunoelectrophoresis (CIE) tests for species identification of imported red meat and offal. AB - From 1 January-31 August, 1984, 585 samples of fresh, uncooked, frozen meat (12) and offal (573) were subjected to the AGID and CIE comparative serological tests for species identification using commercially produced bovine, ovine, porcine and equine anti-species antisera. Species were identified in 286 585 (48.9%) and 581 585 (99.3%) samples by the AGID and CIE tests, respectively. Single species per sample were identified in 246 585 (42.1%) and 481 585 (82.2%) by the AGID and CIE tests. More than one species per sample were identified in 40/585 (6.8%) and 100/585 (17.0%) samples for the same two tests, respectively. The CIE test was more sensitive and rapid in detecting species. PMID- 22056170 TI - The effect of cooking temperature on the functional properties of beef proteins: The role of ionic strength, pH, and pyrophosphate. AB - This study examined the effect of ionic strength (0.12 to 0.52), pH (5.50 and 6.00), pyrophosphate (PP) concentration (0 and 0.31%) and cooking temperature (52 to 87 degrees C) on the cook yield (CY) and tensile strength (TS) of beef homogenates. Increasing the ionic strength, pH and pyrophosphate concentration increased the temperature at which cooking loss first occurred and decreased the temperature required for maximum TS. For most treatments, ionic strengths between 0.32 and 0.42 prevented cooking loss at all temperatures; the lower ionic strengths were required at the higher pH and PP concentration. Maximum TS occurred at 66 degrees C for treatments that had no cooking loss between 60 degrees and 75 degrees C. For treatments that had cooking loss in this temperature range, TS increased linearly with increasing temperature; however, the TS values of these treatments were much lower than those in the former category. CY and TS were optimized by heating to 66 degrees C. PP had a positive effect on both functional properties at ionic strengths >0.25 but a negative effect at ionic strengths <0.25. PMID- 22056171 TI - Influence of breed and muscle metabolic type on muscle glycolytic potential and meat pH in pigs. AB - Glycolytic potential and activities of myofibrillar ATPase, lactate dehydrogenase, citrate synthase, glycogen synthetases and glycogen phosphorylases were measured in five muscles from five Large White, eight Pietrain, seven Belgian Landrace and eight Penshire pigs (Penshire is a composite line including 50% Hampshire, 35% Duroc and 15% Large White blood). Additionally, ultimate pH was measured on the loin and four ham muscles. Muscles could be classified as follows on the basis of enzyme activities: Longissimus dorsi and Semimembranosus as 'fast white', Rectus abdominis as 'intermediate'. Trapezius and Masseter as 'slow red'. Small breed differences were observed in enzyme activities except for citrate synthase activity and degree of activation of glycogen phosphorylase in the 'fast white' muscles. Large Whites, Pietrains and Belgian Landraces did not differ in glycolytic potential whatever the muscle involved. Compared with these three breeds, Penshires had much higher glycolytic potential values in the 'fast white' muscles (+51 to 75%) and in the 'intermediate' muscle (+29 to 56%). However, in the 'slow red' muscles, there was almost no difference in this trait between the four breeds. The Penshire pigs showed lower ultimate pH than the pigs from the other breeds in three of the four ham muscles studied. It is concluded that muscle metabolic type must be considered when assessing breed variation in glycolytic potential, and that the high muscle glycolytic potential characterizing the Hampshire could be inherited as a dominant trait in Hampshire crosses. PMID- 22056172 TI - Feedlot performance and carcass evaluation of heifers fed finishing diets as weanling calves or as yearlings. AB - Twenty commercial Herefored, Angus and Hereford * Angus, weanling and yearling heifers from the same herd were compared for feedlot performance and certain carcass characteristics. Yearlings tended to gain weight more rapidly than did weanlings. Since the cattle were group-fed, no analyses of feed efficiency could be performed. Yearlings appeared, however, to require less feed per unit of gain. The cattle were slaughtered when live weight approached 443 kg. Weanlings were fatter; had more kidney, pelvic and heart fat; merited higher (less desirable) USDA yield grades; had more desirable USDA quality grades and higher dressing percentage (P<0.05) than did yearlings. Ribeye area was not different between treatments. Yearlings yielded a higher percentage of closely trimmed retail lean cuts than did weanlings (P < 0.05). Sensory panel scores were higher (more desirable) for weanlings than for yearlings for both ribeye and inside round steaks (P < 0.05), while no differences were identified for flavor, juiciness or overall palatability of steaks. Warner-Bratzler shear force data generally supported taste panel evaluations for tenderness. These data suggest that carcass composition is impacted by the way cattle are managed and refute the idea that cattle have the same body composition at a given weight regardless of age at slaughter or nutrient density of the diet during finishing. PMID- 22056173 TI - Letter to the editor. PMID- 22056174 TI - [Multiple ossifying trichilemmal cysts of the scalp: a familial case]. AB - INTRODUCTION: The trichilemmal cyst, also called pilar cyst, is a dermal epithelial cyst originating from the pilar follicle. It usually occurs in the scalp. Hereditary and ossifying cases are rare. CASE REPORT: We report the case of a 61-year-old woman presenting with familial multiple trichilemmal cysts, located in the scalp. The histological examination after surgical exeresis confirmed the diagnosis. The trichilemmal cysts featured intra-cystic ossification. The wide dimension of the lesions dimension imposed an extensive surgical scalp exeresis. Reconstruction was performed with a flap after skin expansion. DISCUSSION: The trichilemmal cyst is a benign tumor of skin appendages with a slow outcome. Multiple locations may require an extensive surgical scalp exeresis and lead to a problematic reconstruction. Hereditary cases require familial follow-up to prevent such problems. PMID- 22056175 TI - [Multiple facial squamous cell carcinomas in a child, revealing a xeroderma pigmentosum]. AB - BACKGROUND: Squamous cell carcinoma of the skin is very rare in children. One of its most common risk factors is xeroderma pigmentosum (XP), an autosomal recessive disease characterized by defective cellular DNA repair, and hypersensitivity to ultraviolet radiation. CASE REPORT: We report a case of XP in a 7-year-old black African boy, revealed by squamous cell carcinomas of the inferior lip and upper left eyelid. DISCUSSION: In sub-Saharan regions, the early diagnosis of XP is difficult because of its uncommon occurrence on black skin and black skin specificities. The strong sun radiation in the tropics and a late diagnosis make XP treatment challenging. Thus, prevention in patients' families is mandatory. PMID- 22056176 TI - Salicylamide and salicylglycine oxidovanadium complexes with insulin-mimetic properties. AB - Reaction of N-(2-hydroxybenzyl)-N-(2-picolyl) glycine (H(2)papy) with VOSO(4) in water gives the oxidovanadium(V) oxido-bridged dimer [{(papy)(VO)}(2) MU-O)] (1). Similarly, reaction of N-(2-hydroxybenzyl) glycine (H(2)glysal) with VOSO(4) gives [(glysal)VO(H(2)O)] (2) and reaction of salicylamide (Hsalam) with VOSO(4) in methanol gives [(salam)(2)VO] (3). The crystal structure of the oxido-bridged complex 1 is reported. The insulin-mimetic activity of all three complexes was evaluated with respect to their ability to phosphorylate protein kinase B (PKB). The speciations of complexes 1 and 2 were studied over the pH range 2-10. Complex 1 shows greater stability over the whole pH range but only 2 and 3 exhibit an insulin-mimetic effect. PMID- 22056177 TI - Effects of tethered ligands and of metal oxidation state on the interactions of cobalt complexes with the 26S proteasome. AB - In this paper we report on the synthesis and characterization of three cobalt complexes described as [Co(II)(L(1))(2)] (1), [Co(II)(L(2))] (2), and [Co(III)(L(1))(2)]ClO(4)(3). These complexes contain the deprotonated forms of the [NN'O] tridentate ligand HL(1) and its newly synthesized [N(2)N'(2)O(2)] hexadentate counterpart H(2)L(2), namely, 2,4-diiodo-6-((pyridine-2 ylmethylamino)methyl)phenol and 6,6'-((ethane-1,2-diylbis((pyridin-2-ylmethyl) azanediyl))bis(methylene))bis(2,4-diiodophenol). Characterizations for 1-3 include electrospray ionization (ESI) spectrometry, infrared, and UV-visible spectroscopies, and elemental analyses. A detailed (1)H-NMR study was conducted for 3 and X-ray structural data was obtained for 2. The viability of this series as potential agents for proteasome inhibition and cell apoptotic induction involving PC-3 cancer cells is presented comparing the behavior of the untethered [NN'O](2) six-coordinate 1 and 3 and the tethered counterpart 2 with a 1:1 metal to-ligand ratio. It is observed that the tethering in 2 decreases inhibition activity. When 1 and 3 are compared, the most inert, but redox-active, cobalt(III) species shows the highest chymotrypsin-like activity inhibition on purified proteasome and PC-3 cancer cells. A hypothesis based on the role of oxidation states for proteasome inhibition is offered. PMID- 22056178 TI - Journal of Inorganic Biochemistry. Special section: special issue: containing contributions from the Second Latin American Meeting on Biological Inorganic Chemistry-LABIC 2010. Preface. PMID- 22056179 TI - [The place of myomectomy in woman of reproductive age]. AB - OBJECTIVE: To define the involvement of myomas and myomectomy in all stages from conception to post-partum in women of reproductive age. MATERIALS AND METHODS: A literature review was conducted using the Medline and Cochrane databases to March 2011 by matching the keywords "fertility, infertility, miscarriage, pregnancy, delivery" with "myomas, fibroids, myomectomy". RESULTS: An association between myomas and fertility has been observed but the responsibility fibroids in infertility remains unclear. Myomas are associated with an increased rate of obstetric complications. Adhesions are the main complication of myomectomy. Endoscopic procedures and the use of anti-adhesive barriers prevent adhesion formation. Pregnancy rate in cases of myomectomy by laparotomy and laparoscopy is similar. Myomectomy during pregnancy is exceptionally indicated. CONCLUSION: The discovery of a uterine myoma needs to consider the responsibility of myomas in infertility, but also its impact on a future pregnancy. The therapeutic management is based on myomectomy but expected benefits must be weighed with potential risks. PMID- 22056180 TI - [Prevention of the complications related to the use of prosthetic meshes in prolapse surgery: guidelines for clinical practice - literature review]. AB - OBJECTIVE: To provide guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF), based on the best evidence available, concerning the adverse events related to surgical procedures involving the use of prosthetic meshes. MATERIALS AND METHODS: French and English-language articles from Medline, PubMed, and the Cochrane Database were searched, using key words (mesh ; pelvic organ prolapse ; cystocele ; rectocele ; uterine prolapse ; complications ; adverse event ; sacral colpopexy ; extrusion ; infection...). RESULTS: As with any surgery, it is recommended to provide a perioperative smoking cessation (expert opinion) and comply with the prevention of nosocomial infections (regulatory requirement). There is no evidence to recommend routine local or systemic estrogen therapy before or after prolapse surgery using mesh, regardless of the surgical approach (grade C). Antibiotic prophylaxis is recommended, regardless of the approach (expert opinion). It is recommended to seek a pre-operative urinary tract infection and treat it (expert opinion). The first cases should be made under the guidance of an experienced surgeon in the relevant technique (grade C). It is recommended not to place a non-absorbable synthetic mesh into the rectovaginal septum when a rectal injury occurs (expert opinion). The placement of a non-absorbable synthetic mesh into the vesicovaginal septum may be considered after the suture of a bladder injury if the suture is considered to be satisfactory (expert opinion). If a synthetic mesh is placed by vaginal route, it is recommended to use a macroporous polypropylene monofilament mesh (grade B). It is recommended not to use polyester mesh for vaginal surgery (grade B). It is allowed to perform a hysterectomy associated with the placement of a non-absorbable synthetic mesh placed by vaginal route but this is not routinely recommended (expert opinion). It is recommended to minimize the extent of the colpectomy (expert opinion). Laparoscopic approach is recommended for sacral colpopexy (grade C). It is recommended not to place and suture meshes by vaginal route when a sacral colpopexy is performed (grade B). It is recommended not to use silicone-coated polyester, porcine dermis, fascia lata, and polytetrafluoroethylene meshes (grade B). It is recommended to use polyester (without silicone coating) or polypropylene meshes (grade C). Suture of the meshes to the promontory can be performed using thread/needle or tacker (grade C). A peritonization is recommended to cover the meshes (grade C). If hysterectomy is required, it is recommended to perform a subtotal hysterectomy (grade C). CONCLUSION: Implementation of this guideline should decrease the prevalence of complications related to surgical procedures involving the use of prosthetic meshes. PMID- 22056181 TI - [Place of fetal heart rate monitoring and its computerized analysis during the surveillance of prolonged pregnancy]. AB - OBJECTIVES: To determine the place and the respective value of both visual and computerized analysis of cardiotocography (CTG) during the surveillance of prolonged pregnancy, to show their potential impacts on the obstetric care according to their results and their possible integration in the surveillance programs of prolonged pregnancies while awaiting better cervical conditions or spontaneous labour. MATERIALS AND METHODS: Bibliographic research by consulting database of both Pubmed and Cochrane Library. RESULTS: In the case of prolonged pregnancy, CTG is the first line examination for the detection of antepartum asphyxia. In the case of prolonged pregnancy, the predictive criteria of acidosis remain unchanged. The use of computerized CTG analysis instead of visual analysis is a possible alternative as it enables to reduce the length and the repetition of the CTGs. It has however not proved its superiority over visual analysis in improving the overall perinatal prognosis of prolonged pregnancies. CONCLUSION: In the case of fetal surveillance in prolonged pregnancies without risks associated, evidence is lacking to attest that the use of visual and computerized CTG analysis improves perinatal prognosis. CTG plays all the same a dominating role in surveillance programs and remains used in the first intention. The contraction stress test and the fetal vibroacoustic stimulation test have not demonstrated their usefulness in this indication. PMID- 22056182 TI - [Epidemiology of prolonged pregnancy: incidence and maternal morbidity]. AB - OBJECTIVE: To estimate the frequency of prolonged pregnancy and study its associated maternal morbidity. METHODS: Abstracts and articles were searched using Pubmed and Cochrane Library. RESULTS: Nearly 15% of pregnant women in France are concerned by prolonged pregnancy (>=41(+0) weeks), whereas post-term pregnancy (>=42(+0) SA) only concern 1% of them. The post-term pregnancy frequency is heterogeneous between Europe and United States. It varies between 0.5% and 10% (EL2). In Europe, Scandinavian countries present discrepancies with high proportions of post-term pregnancies between 5 and 7%. These observations identified time variations and variations between countries. They can be explained by two factors: pregnancy datation by ultrasound and the evolution of labor induction practices. Moreover, post-term pregnancy constitute a risk factor of maternal complications as: cesarean section, postpartum haemorrhages, infections and perineum lacerations (EL2). On the contrary, limited conclusions about associations between prolonged pregnancies and labor inductions are due to insufficient data and the lack of high quality studies. Nowadays, we still ignore if labor inductions in the particular context of prolonged pregnancies are associated or not to an increase of maternal morbidities. CONCLUSION: Prolonged pregnancy is associated with an excess of maternal morbidity. PMID- 22056183 TI - [Definitions of expected date of delivery and post-term delivery]. AB - The duration of pregnancy is between 280 and 290 days from the first day of the last menstrual period and varies according to the literature, the authors, the calculation methods and the characteristics of women. Assuming that the date of beginning of pregnancy is known, the expected date of delivery varies depending on the length of gestation. Thus, in literature and in obstetric practice, there is no consensus on the definition of expected date of delivery. From a medical point of view, it seems important to fix the date from which the monitoring should start and from which an induction of labour should be considered. Thus, arbitrarily, we can consider that the term period corresponds to a time interval located between 37(+0) SA and 41(+6) SA and the post-term period begins from 42(+0) SA. Because maternal and fetal risks increase at the end of the pregnancy, one can speak, arbitrarily, of prolonged pregnancy from 41(+0) SA (expert opinion). PMID- 22056184 TI - [Prevention of the complications related to the use of prosthetic meshes in prolapse surgery: guidelines for clinical practice - text of the guidelines]. PMID- 22056185 TI - [Prolonged pregnancy: when should surveillance be started and what should be the frequency?]. AB - OBJECTIVE: To determine when surveillance should be started in prolonged pregnancy and what would be the more appropriate frequency for it. STUDY DESIGN: Systematic searches of Medline and the Cochrane Library were performed. RESULTS: Fetal mortality diminishes from 37 weeks of gestation to a nadir of one death for 1000 births at 40(+0) weeks. It increases thereafter up to three deaths for 1000 births at 43(+0) weeks. Perinatal mortality rates show same pattern and is estimated to be of two and four to six deaths for 1000 births at 41(+0) and 43(+0) weeks, respectively. However, current available data does not allow for the determination of a gestational age cut-off associated with major increase of perinatal mortality and on which surveillance of prolonged pregnancy should be genuinely started. French epidemiological data from 2003 indicate that although 52.5% of pregnant women have reached 40(+0) weeks only 20,7% and 1% have reaches 41(+0) and 42(+0) weeks, respectively. Intrauterine fetal growth associated with prolonged pregnancy increases perinatal mortality. In most randomized trials having compared labour induction with expectant management, fetal surveillance was started at 41(+0) weeks. CONCLUSION: Due to the increased risk of perinatal mortality, it seems appropriate that fetal surveillance is started at 41(+0) weeks (expert opinion). This implies a rational organization of care to support surveillance of 20% of pregnant women. The frequency of this monitoring consisting of at least twice-weekly cadiotocography and ultrasound estimation of amniotic fluid (expert opinion). PMID- 22056186 TI - [Fetal and neonatal complications related to prolonged pregnancy]. AB - OBJECTIVE: To evaluate fetal and neonatal outcomes related to prolonged pregnancy. METHODS: This study is based on Pubmed search, Cochrane library and HAS recommendations. RESULTS: The risk of fetal complications including macrosomia (6 %), oligohydramnios (10 %-15 %), abnormal fetal heart rate pattern and meconium-stained fluid is increased in prolonged pregnancy (>= 41(+0) weeks). The rate of stillbirth was estimated between 1.6 0/00 and 3.0 0/00 live births according to countries in post-term pregnancies (>= 42(+0) weeks). The risk of umbilical cord pH less than 7.10, Apgar score at five minutes inferior to 7, ICU admissions and perinatal asphyxia is increased in post-term infants (>= 42(+0) weeks) compared with term infants. The risk of neurologic complications including neonatal convulsion, hypoxic ischemic encephalopathy, cerebral palsy, developmental deviations and epilepsy in childhood is increased in post-term infants. The risk of meconium aspiration syndrome, neonatal sepsis, and birth trauma including shoulder dystocia and bone fracture is increased in post-term infants. The rate of perinatal mortality increases in post-term infants. The perinatal mortality in post-term infants could be explained by perinatal asphyxia and meconium aspiration syndrome. CONCLUSIONS: The risk of perinatal complications and mortality are increased in prolonged pregnancy. PMID- 22056187 TI - [Update of myoma management - introduction]. PMID- 22056188 TI - [Different methods for the induction of labour in postterm pregnancy]. AB - OBJECTIVES: Define methods of induction of labour for the population of pregnant women at the end of 41 SA and beyond, including membranes sweeping, mechanical and pharmacological procedures as oxytocin, prostaglandin E1 (misoprostol) and E2 (dinoprostone) and other methods as well for the scarred uterus. METHODS: Bibliographic research done by consulting databases PubMed, and Cochrane. RESULTS: Membrane sweeping reduces by 41% the need of induction of labour at 41 SA and 72% for postterm (42 SA). Membrane sweeping is a technique with some discomfort for the patient but has advantages. This procedure should not be imposed on patients in a systematic visit because it presents inconveniences (contractions, bleeding, pain). Oxytocin remains the gold standard used for labour induction and requires well-codified rationale protocols in maternity for increasing doses. Most of the trials show that this product is appropriate when the cervix is considered as favorable (Bishop >= 6). In the presence of intact membranes, induction by oxytocin must be associated with amniotomy for a significant reduction in "induction-delivery" period. The Foley catheter is a mechanically reliable, reproducible method for inducing labour with less uterine hyperstimulation without increasing the rate of caesarean sections. It is an interesting process but maternal and neonatal infectious morbidity appears to be possibly increased. The non-vaginal PGE2 (cervical) are no longer recommended. The PGE2 vaginal gel or pessary are comparable methods to induce labour. They can be used to successfully induce labour regardless of cervical Bishop score. In case of unfavorable cervical conditions, PGE2 can reduce the use of oxytocin and decrease the required doses. Misoprostol is a molecule that may be proposed for induction of labour provided to know the doses, risks and side effects and to adapt materno-fetal monitoring. The optimal route of administration remains yet to be assessed because of a higher risk of hyperstimulation or tachysystole. Initial doses should be 25 MUg. However, misoprostol did not have the authorization in this indication and merit some caution when using it. Prostaglandin E1 is associated with a high risk of uterine rupture and should not be used after caesarean section. Acupuncture, homeopathy NO donors, breast stimulation or sexual intercourse are methods ineffective in all conditions or assessment is insufficient to conclude with evidence based medicine. CONCLUSION: In postterm, different procedures could be performed for induction of labour. Furthermore membrane sweeping, oxytocin is the drug of choice for induction on favourable cervix and one of the most commonly used drugs. Vaginal prostaglandins E2 are effective whatever the cervical conditions. Misoprostol is a very interesting pharmacological molecule without authorization in this indication but has real advantages on efficacy, cost, storage and administration. Other studies with high power have to remain on track and to focus on the optimal and route doses because of increased risk of tachysystole or hyperstimulation with effects on the FHR. Minimal doses at 25MUg seem to be safe. The Foley catheter is a reliable method without any pharmacological effect and opening interesting perspectives but with caution about the possible increased infectious risks. PMID- 22056189 TI - [Except fertility, place of myomectomy in perimenopause and after menopause]. AB - More and more perimenopausal and menopausal women seek an alternative to hysterectomy because they desire future pregnancy or wish to retain their uteri even if they have completed childbearing. Myomectomy may be an option. We can't know the evolution of leiomyomas. Hysteroscopic myomectomy is the treatment of submucous fibromas. Recurrence and subsequent surgery occurs in 16 to 21 % of cases. Intramural and subserousal myomas can be treated by myomectomy. Myomectomy should be performed laparoscopically because of shorter hospital stay, faster recovery and reduced postoperative pain. Second surgery is needed in 4-16 % of patients. If hysterectomy is performed, it should be by vaginal or laparoscopic route. There is no difference in perioperative morbidity between hysterectomy and myomectomy. Intra- and postoperative complications are similar between myomectomy and hysterectomy. Hysterectomy may be prefered if there is risk factor of malignancy or if the fibroma is discovered or has a rapid growth after menopause. PMID- 22056190 TI - [Management of post-term neonates]. AB - OBJECTIVE: To estimate the modalities of management of post-term neonates. METHODS: This study is based on PubMed search, Cochrane library and HAS recommendations. RESULTS: Medical team should be able to provide neonatal resuscitation in delivery room in case of meconium-stained fluid or perinatal asphyxia according to the international guidelines ILCOR 2010. The glycaemia of the post-term newborn with macrosomia should be evaluated. The initial clinical examination should search complications such as shoulder dystocia or clavicular fracture. Full blood count should be performed in symptomatic newborn post-term. Developmental assessment should be performed in post-term newborn in case of associated pathology. CONCLUSIONS: The risk of perinatal complications is increased in newborn post-term in delivery room and during hospitalization. Medical team should be able to manage these complications. PMID- 22056191 TI - [Update of myoma management - method and organization]. PMID- 22056192 TI - [How to date pregnancy?]. AB - Accurate gestational assessment is essential for adequate growth assessment, appropriate aneuploidy screening and correct management of term. Based on expert opinion and beside ART pregnancies, it is recommended to use crown-rump length (CRL) to determine date of conception whenever there is an appropriate measurement taken at 11-14 weeks. This allows accurate dating at approximately 5 days in 95% of cases. PMID- 22056193 TI - [Myomectomy for infertile women: the role of surgery]. AB - At present, it is estimated that fibroids may be associated with infertility in 5 to 10% and are possibly the sole cause of infertility in 1 to 3%. Their effects on fertility remain debated. The aim of this review of published studies between January 1990 and November 2010 was to clarify the relation between myoma and fertility, and to assess the role of myomectomy in infertile patients. In assisted reproduction technology and spontaneous conception, hysteroscopic sub mucous myoma resection increased pregnancy rates. Intramural fibroids appear to decrease fertility, but the myomectomy does not improve assisted reproduction technology and spontaneous fertility. More high-quality studies are needed to conclude toward the value of myomectomy for intramural fibroids. Subserosal fibroids do not affect fertility outcomes, and removal does not confer benefit. PMID- 22056194 TI - [Guidelines for clinical practice concerning the prevention of the complications related to the use of prosthetic meshes in prolapse surgery: methods]. PMID- 22056195 TI - [To evaluate the role of fetal movement counting and amnioscopy in the management of prolonged pregnancies]. AB - OBJECTIVES: To evaluate the role of fetal movement counting and amnioscopy in the management of prolonged pregnancies. MATERIALS AND METHODS: PubMed and the Cochrane library were searched using terms: fetal movement counting, decreased fetal movement, post-term pregnancy, late pregnancy, prolonged pregnancy, postdate pregnancy, amnioscopy, meconium amniotic fluid, surveillance of the fetus. RESULTS: Decreased fetal mouvements (DFM) in prolonged pregnancies is a frequent cause of unplanned visits. For many authors, the best criterion is the self-perception of reduced maternal or any change of fetal movement. Current data is insufficient to show a link between DFM and increased fetal morbidity and mortality. It is reasonable to recommend to the patient to consult in case of DFM and make an assessment of fetal vitality (experts' opinion). Current data are insufficient to show a potential benefit of the establishment of an information given to patients on DFM in prolonged pregnancy (experts' opinion). No fetal movement counting was assessed in the prolonged pregnancy. High negative predictive value of amnioscopy explains it is reassuring only if the amniotic fluid is clear. Amnioscopy showed no neonatal benefit in the survey of prolonged pregnancies (NP4). CONCLUSION: In the prolonged pregnancies, no fetal movement counting can reduce the perinatal morbidity and mortality rate. The interest of amnioscopy in the survey of prolonged pregnancies has never been showed. It is not recommended to use it. PMID- 22056196 TI - [Antidotes: use guidelines and minimun stock in an emergency department]. AB - OBJECTIVE: To develop a guide for antidotes and other medications used to counteract poisoning, and define the stock in an emergency department, as a safety priority for the part-time pharmacist assigned to the unit. METHOD: A search of specialist databases and web portals of the Spanish Society of Toxicology and the British National Poisons Information Service, as well as toxicology databases, TOXICONET, information from other hospitals, tertiary sources, Micromedex and Medline. RESULTS: The Guide contains 42 active ingredients and is accessible to the Pharmacy and Emergency departments in electronic format. A minimum emergency stock was agreed based on the daily treatment of a 100 kg patient. This information, including updated expiry dates, is available at the emergency department antidote stock facilities and in electronic format. On a monthly basis, the pharmacist reviews the need to replace any drugs, due to their expiry date or lack of use. DISCUSSION: The lack of evidence from high quality antidote studies, the variability due to the difficulties of updating sources and some geographical differences in their use means that decision-making can be difficult. It would be useful to have minimum quantity recommendations from societies of toxicology, regulatory agencies and organisations such as the Joint Commission on the Accreditation of Healthcare Organisations. It would also be useful to have a suprahospital risk assessment to optimise management and ensure the availability of antidotes which are expensive, have a limited shelf life, or of which demand is difficult to forecast. PMID- 22056197 TI - Kinetics of the cervical spine in pediatric and adult volunteers during low speed frontal impacts. AB - Previous research has quantified differences in head and spinal kinematics between children and adults restrained in an automotive-like configuration subjected to low speed dynamic loading. The forces and moments that the cervical spine imposes on the head contribute directly to these age-based kinematic variations. To provide further explanation of the kinematic results, this study compared the upper neck kinetics - including the relative contribution of shear and tension as well as flexion moment - between children (n=20, 6-14 yr) and adults (n=10, 18-30 yr) during low-speed (<4 g, 2.5 m/s) frontal sled tests. The subjects were restrained by a lap and shoulder belt and photo-reflective targets were attached to skeletal landmarks on the head, spine, shoulders, sternum, and legs. A 3D infrared tracking system quantified the position of the targets. Shear force (F(x)), axial force (F(z)), bending moment (M(y)), and head angular acceleration (theta(head)) were computed using inverse dynamics. The method was validated against ATD measured loads. Peak F(z) and theta(head) significantly decreased with increasing age while M(y) significantly increased with increasing age. F(x) significantly increased with age when age was considered as a univariate variable; however when variations in head-to-neck girth ratio and change in velocity were accounted for, this difference as a function of age was not significant. These results provide insight into the relationship between age based differences in head kinematics and the kinetics of the cervical spine. Such information is valuable for pediatric cervical spine models and when scaling adult-based upper cervical spine tolerance and injury metrics to children. PMID- 22056198 TI - Influence of kinematic analysis methods on detecting ankle and subtalar joint instability. AB - Patients with subtalar joint instability may be misdiagnosed with ankle instability, which may lead to chronic instability at the subtalar joint. Therefore, it is important to understand the difference in kinematics after ligament sectioning and differentiate the changes in kinematics between ankle and subtalar instability. Three methods may be used to determine the joint kinematics; the Euler angles, the Joint Coordinate System (JCS) and the helical axis (HA). The purpose of this study was to investigate the influence of using either method to detect subtalar and ankle joints instability. 3D kinematics at the ankle and subtalar joint were analyzed on 8 cadaveric specimens while the foot was intact and after sequentially sectioning the anterior talofibular ligament (ATFL), the calcaneofibular ligament (CFL), the cervical ligament and the interosseous talocalcaneal ligament (ITCL). Comparison in kinematics calculated from sensor and anatomical landmarks was conducted as well as the influence of Euler angles and JCS rotation sequence (between ISB recommendation and previous research) on the subtalar joint. All data showed a significant increase in inversion when the ITCL was sectioned. There were differences in the data calculated using sensors coordinate systems vs. anatomic coordinate systems. Anatomic coordinate systems were recommended for these calculations. The Euler angle and JCS gave similar results. Differences in Euler angles and JCS sequence lead to the same conclusion in detecting instability at the ankle and subtalar joint. As expected, the HA detected instability in plantarflexion at the ankle joint and in inversion at the subtalar joint. PMID- 22056199 TI - Education halves the risk of dementia due to apolipoprotein epsilon4 allele: a collaborative study from the Swedish brain power initiative. AB - A number of studies have explored the relationships of apolipoprotein E (APOE) genotype and education with dementia over the last decade. However, observations concerning the possible modifying effect of education on the APOE-dementia association are limited. The objective of this study was to test the hypothesis that education may decrease the risk of APOE epsilon4 on dementia. Pooled data from 3 major population-based studies in Northern Europe were used in this study, with a total of 3436 participants aged 65 and older derived from the Kungsholmen project and the Gothenburg Birth Cohort studies in Sweden, and the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) project in Finland. The main outcome measure was dementia, which was diagnosed in 219 persons according to standard criteria. APOE epsilon4 was associated with increased risk of dementia independent of the effect of education (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.9-3.4 for 1 epsilon4 carrier and OR, 3.7; 95% CI, 1.8-7.2 for 2 epsilon4 carriers). High education (8 years and more) was related to a lower dementia risk (OR, 0.5; 95% CI, 0.3-0.6). An interaction between education and APOE epsilon4 was observed. Compared with those with less education and no epsilon4, the odds of dementia among persons with low education who carried any epsilon4 allele was 2.7 (95% CI, 1.9-3.9), and 1.2 (0.7-1.8) if they had higher education. This study suggests that genetic (APOE epsilon4) and environmental (education) factors are not only independently but also interactively related to dementia risk and that high education may buffer the negative effect of APOE epsilon4 on dementia occurrence. PMID- 22056200 TI - Salubrinal attenuates beta-amyloid-induced neuronal death and microglial activation by inhibition of the NF-kappaB pathway. AB - Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid (Abeta) peptides in the brain, inducing neuronal cell death and microglial activation. Endoplasmic reticulum (ER) stress has been proposed to be a mediator of Abeta neurotoxicity. In this study, we test whether salubrinal, an ER stress inhibitor, can protect against Abeta-mediated neurotoxicity. We show in rat primary cortical neurons and mouse microglial BV-2 cells that short-term treatment with salubrinal attenuates Abeta-induced neuronal death and microglial activation. Remarkably, our results show that salubrinal's neuroprotective effects are not due to inhibition of ER stress. Rather, we demonstrate that salubrinal exerts its effects through the inhibition of IkappaB kinase (IKK) activation, IkappaB degradation, and the subsequent nuclear factor-kappa B (NF kappaB) activation. These results elucidate inhibition of the NF-kappaB pathway as a new mechanism responsible for the protective effects of salubrinal against Abeta neurotoxicity. This study also suggests that modulation of Abeta-induced NF kappaB activation could be a potential therapeutic strategy for Alzheimer's disease. PMID- 22056202 TI - Advocating for safety in the workplace. PMID- 22056203 TI - Interactions among benzodiazepine and buprenorphine/naloxone. PMID- 22056201 TI - Altered age-related trajectories of amygdala-prefrontal circuitry in adolescents at clinical high risk for psychosis: a preliminary study. AB - Emotion processing deficits are prominent in schizophrenia and exist prior to the onset of overt psychosis. However, developmental trajectories of neural circuitry subserving emotion regulation and the role that they may play in illness onset have not yet been examined in patients at risk for psychosis. The present study employed a cross-sectional analysis to examine age-related functional activation in amygdala and prefrontal cortex, as well as functional connectivity between these regions, in adolescents at clinical high risk (CHR) for psychosis relative to typically developing adolescents. Participants (n=34) performed an emotion processing fMRI task, including emotion labeling, emotion matching, and non emotional control conditions. Regression analyses were used to predict activation in the amygdala and ventrolateral prefrontal cortex (vlPFC) based on age, group, sex, and the interaction of age by group. CHR adolescents exhibited altered age related variation in amygdala and vlPFC activation, relative to controls. Controls displayed decreased amygdala and increased vlPFC activation with age, while patients exhibited the opposite pattern (increased amygdala and decreased vlPFC activation), suggesting a failure of prefrontal cortex to regulate amygdala reactivity. Moreover, a psychophysiological interaction analysis revealed decreased amygdala-prefrontal functional connectivity among CHR adolescents, consistent with disrupted brain connectivity as a vulnerability factor in schizophrenia. These results suggest that the at-risk syndrome is marked by abnormal development and functional connectivity of neural systems subserving emotion regulation. Longitudinal data are needed to confirm aberrant developmental trajectories intra-individually and to examine whether these abnormalities are predictive of conversion to psychosis, and of later deficits in socioemotional functioning. PMID- 22056205 TI - A 68-year-old man with bright red emesis. PMID- 22056207 TI - T cell receptor signalling in gammadelta cell development: strength isn't everything. AB - gammadelta cells have been conserved across ~450 million years of evolution, from which they share the distinction, alongside alphabeta T cells and B cells, of forming antigen receptors by somatic gene recombination. However, much about these cells remains unclear. Indeed, although gammadelta cells display 'innate like' characteristics exemplified by rapid tissue-localised responses to stress associated stimuli, their huge capacity for T cell receptor (TCR)gammadelta diversity also suggests 'adaptive-like' potential. Clarity requires a better understanding of TCRgammadelta itself, not only through identification of TCR ligands, but also by correlating thymic TCRgammadelta signalling with commitment to gammadelta effector fates. Here, we propose that thymic TCRgammadelta-ligand engagement versus ligand-independent signalling differentially imprints innate like versus adaptive-like characteristics on developing gammadelta cells, which fundamentally dictate their peripheral effector properties. PMID- 22056208 TI - Rabbit model of primary hyperparathyroidism induced by high-phosphate diet. AB - The objective of this study is to establish a new rabbit model of primary hyperparathyroidism (PHPT) induced by high-phosphate diet. One hundred twenty rabbits were divided into two groups of 60 each. The treatment group was fed a high-phosphate diet (Ca:P = 1:7) and the control group was given a normal animal diet (Ca:P = 1:0.7) for 1 to 6 mo. Serologic examinations, including parathyroid hormone (PTH), calcium and phosphorus levels, blood urea nitrogen, creatinine, and uric acid, and the histologic examination, including parathyroid, kidney, and bones, were performed at the end of each month for 6 mo. Compared with the control, serum PTH levels in the treatment groups were elevated at all six time points, whereas serum calcium levels were reduced, and serum phosphorus levels remain unchanged over the course of the first 3 mo. Serum calcium levels were increased, whereas serum phosphorus levels were reduced at 4, 5, and 6 mo. Parathyroid histopathological examination showed no change during the first month, whereas 60% of the animals exhibited mild hyperplasia starting at 2 mo, and 90% of the animals in the treatment group exhibited mild-to-moderate hyperplasia with gland enlargement starting from 3 mo through the end of the study. Histopathological examination of the kidneys showed no change at 1 mo, but focal parenchymal inflammation with calcium deposition was observed in the treatment groups at 2 to 6 mo. Fibrous tissue of the bone extended toward the cortex, and fibrosis was evident at the third month. The fibrous cells were found to be concentrated mainly on the inner and outer membranes of the bone cortex, and the amount of fibrous tissue increased as the disease progressed. We conclude that a new rabbit animal model of PHPT can be successfully created by the administration of a high-phosphate diet. This animal model can be used in various future studies related to PHPT. PMID- 22056209 TI - Effects of calcium salts of long-chain fatty acids and rumen-protected methionine on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide and pancreatic hormones in lactating cows. AB - Our objective was to determine the effects of calcium salts of long-chain fatty acids (CLFAs) and rumen-protected methionine (RPM) on plasma concentrations of ghrelin, glucagon-like peptide-1 (7 to 36) amide, and pancreatic hormones in lactating cows. Four Holstein cows in midlactation were used in a 4 by 4 Latin square experiment in each 2-wk period. Cows were fed corn silage-based diets with supplements of CLFAs (1.5% added on dry matter basis), RPM (20 g/d), CLFAs plus RPM, and without supplement. Jugular blood samples were taken from 1 h before to 2 h after morning feeding at 10-min intervals on day 12 of each period. CLFAs decreased dry matter intake, but RPM did not affect dry matter intake. Both supplements of CLFAs and RPM did not affect metabolizable energy intake and milk yield and composition. Plasma concentrations of NEFAs, triglyceride (TG), and total cholesterol (T-Cho) were increased with CLFAs alone, but increases of plasma concentrations of TG and T-Cho were moderated by CLFAs plus RPM. Calcium salts of long-chain fatty acids increased plasma ghrelin concentration, and the ghrelin concentration with CLFAs plus RPM was the highest among the treatments. Plasma concentrations of glucagon-like peptide-1, glucagon, and insulin were decreased with CLFAs, whereas adding RPM moderated the decrease of plasma glucagon concentration by CLFAs. These results indicate that the addition of methionine to cows given CLFAs increases plasma concentrations of ghrelin and glucagon associated with the decrease in plasma concentrations of TG and T-Cho. PMID- 22056210 TI - The experience of agency in sequence production with altered auditory feedback. AB - When speaking or producing music, people rely in part on auditory feedback - the sounds associated with the performed action. Three experiments investigated the degree to which alterations of auditory feedback (AAF) during music performances influence the experience of agency (i.e., the sense that your actions led to auditory events) and the possible link between agency and the disruptive effect of AAF on production. Participants performed short novel melodies from memory on a keyboard. Auditory feedback during performances was manipulated with respect to its pitch contents and/or its synchrony with actions. Participants rated their experience of agency after each trial. In all experiments, AAF reduced judgments of agency across conditions. Performance was most disrupted (measured by error rates and slowing) when AAF led to an ambiguous experience of agency, suggesting that there may be some causal relationship between agency and disruption. However, analyses revealed that these two effects were probably independent. A control experiment verified that performers can make veridical judgments of agency. PMID- 22056211 TI - [Clustered cases of intrafamily invasive Streptococcus pyogenes infection (or group A streptococcus)]. AB - Streptococcus pyogenes or group A streptococcus (GAS) is responsible for serious invasive infections with a risk of secondary infection in patients with more contact than in the general population. Regardless of clustering, few intrafamilial invasive infections have been reported despite a recent increase in the incidence of invasive GAS disease. We report the cases of two brothers, one a boy of 8.5 years with toxic shock syndrome with no bacteria identified and the second, 1 week later, his 14.5-year-old brother in hospital for sepsis due to GAS. The occurrence of a confirmed case of invasive GAS and a probable case within such a short period met the definition of clustered cases. Both brothers showed no risk factors for invasive disease and no gateway including skin was found. Antibiotic therapy was initiated in the family as recommended by the French Higher Council of Public Hygiene. PMID- 22056212 TI - Outcome assessment of patients with metastatic renal cell carcinoma under systemic therapy using artificial neural networks. AB - BACKGROUND: The outcome of patients with advanced renal cell carcinoma (RCC) under systemic therapy shows remarkable variability, and there is a need to identify prognostic parameters that allow individual prognostic stratification and selection of optimal therapy. Artificial neural networks (ANN) are software systems that can be trained to recognize complex data patterns. In this study, we used ANNs to identify poor prognosis of patients with RCC based on common clinical parameters available at the beginning of systemic therapy. PATIENTS AND METHODS: Data from patients with RCC who started systemic therapy were collected prospectively in a single center database; 175 data sets with follow-up data (median, 36 months) were available for analysis. Age, sex, body mass index, performance status, histopathologic parameters, time interval between primary tumor and detection of metastases, type of systemic therapy, number of metastases, and metastatic sites were used as input data for the ANN. The target variable was overall survival after 36 months. Logistic regression models were constructed by using the same variables. RESULTS: Death after 36 months occurred in 26% of the patients in the tyrosine kinase inhibitors group and in 37% of the patients in the immunotherapy group (P = .22). ANN achieved 95% overall accuracy and significantly outperformed logistic regression models (78% accuracy). Pathologic T classification, invasion of vessels, and tumor grade had the highest impact on the network's decision. CONCLUSION: ANN is a promising approach for individual risk stratification of patients with advanced RCC under systemic therapy, based on clinical parameters, and can help to optimize the therapeutic strategy. PMID- 22056213 TI - Metastatic clear cell adenocarcinoma of the urethra in a male patient: report of a case. PMID- 22056214 TI - Weight change modulates epicardial fat burden: a 4-year serial study with non contrast computed tomography. AB - INTRODUCTION: Epicardial fat volume (EFV) is linked to cardiovascular event risk. We aimed to investigate the relationships between EFV and weight change. METHODS: From the EISNER (Early Identification of Subclinical Atherosclerosis using Non invasive Imaging Research) Registry with baseline and follow-up coronary calcium scans (1248 subjects), we selected a cohort of 374 asymptomatic subjects matched using age decade, gender and coronary calcium score (CCS) as a measure of subclinical cardiovascular risk, who underwent 2 scans at an interval of 4.1+/ 0.4 years. Using semi-automated validated software, pericardial contours were generated on all slices by spline interpolation from 5 to 10 control points. EFV was computed as fat volume within the pericardial contours. Weight gain/loss was defined as >5% change. RESULTS: At baseline, EFV was moderately correlated to weight, body mass index (BMI) and waist circumference (r=0.51, 0.41 and 0.50, p<0.0001). EFV change was weakly correlated to change in weight (r=0.37, p<0.0001), BMI (r=0.39, p<0.0001) and waist circumference (r=0.21, p=0.002). On multivariable linear regression analysis, weight change [beta=1.2, 95% confidence interval (CI) 0.9-1.5, p<0.001], BMI change (beta=1.2, 95% CI 0.9-1.5, p<0.001), gender (beta=-6.4, 95% CI -10.9 to -1.8, p=0.006) and hypertension (beta=4.7, 95% CI 0.5-9.0, p=0.03) predicted EFV change. EFV decreased in 54 subjects with weight loss and increased in 71 subjects with weight gain (-2.3+/-21.1% vs. 23.3+/-24.4%, p<0.001). CONCLUSIONS: EFV is related to body weight, BMI and waist circumference. Reduction in weight may stabilize or reduce EFV, while weight gain may promote EFV increase. PMID- 22056215 TI - Qualitative characteristics of HDL in young patients of an acute myocardial infarction. AB - AIM: Recently, the concept that high density lipoprotein (HDL) quality is an important parameter for atheroprotection is gaining ground, though little data exists so far to support it. In an attempt to identify measurable qualitative parameters of HDL associated with increased risk for premature myocardial infarction (MI), we studied the structural characteristics of HDL from patients who survived an MI at a young age (<=35 years). METHODS AND RESULTS: We studied 20 MI patients and 20 healthy control subjects. HDL of patients had reduced apolipoprotein A-I (apoA-I), apolipoprotein M, and paraoxonase 1 levels and significantly elevated apolipoprotein C-III (apoCIII) levels (all p<0.05). Specifically, the HDL apoA-I/apoC-III ratio was 0.24+/-0.01 in patients versus 4.88+/-0.90 in controls (p<0.001). These structural alterations correlated with increased oxidation potential of HDL of the MI group compared to controls (2.5 fold, p=0.026). Electron microscopy showed no significant difference in average HDL particle diameter between the two groups though a significant difference existed in HDL diameter distribution, suggesting the presence of different HDL subpopulations in MI and control subjects. Indeed, non-denaturing two-dimensional electrophoresis revealed that MI patients had reduced pre-beta1(alpha), pre beta1(b) and alpha(2), and elevated alpha(1), alpha(3), and pre-alpha(4) HDL. CONCLUSIONS: Reduction in the HDL apoA-I/apoC-III ratio, changes in the HDL subpopulation distribution and an increase in HDL oxidation potential correlated with the development of MI in young patients. The possibility that such changes may serve as markers for the early identification of young individuals at high risk for an acute coronary event should be further explored. PMID- 22056216 TI - CRP and CD14 polymorphisms correlate with coronary plaque volume in patients with coronary artery disease--IVUS substudy of the ENCORE trials. AB - BACKGROUND: Several proinflammatory single-nucleotide polymorphisms (SNPs) have been linked to the progression of atherosclerosis and coronary artery disease (CAD). Plaque size and its destabilization by inflammatory processes are major determinants of ischemia and acute coronary syndromes. Intravascular ultrasound (IVUS) allows for quantification of plaque size in vivo. We therefore investigated the relation of plaque size with mutations of proinflammatory genes in patients with CAD. METHODS: In 196 patients with stable CAD enrolled in the ENCORE trials coronary plaque and vessel volume was assessed by IVUS. 173 patients were successfully genotyped for polymorphisms of proinflammatory genes CD14 C(-260)T and CRP C(+1444)T using the single-nucleotide polymorphism polymerase chain reaction (SNP PCR) approach. RESULTS: Baseline characteristics were comparable for all genotype groups. Higher ratios of plaque volume/vessel volume were observed in patients with the CRP 1444TT (n=11) and CD14 260TT (n=33) genotypes (p=0.016 and p=0.026, respectively). CONCLUSION: In patients with stable coronary artery disease the CRP 1444TT and CD14 260TT variants are associated with larger coronary plaque volume independently of concomitant cardiovascular risk factors. PMID- 22056217 TI - The theory of planned behavior: precursors of marijuana use in early adolescence? AB - BACKGROUND: Precursors of marijuana use in early adolescence are largely unknown because studies generally focus on marijuana use among older adolescents or adults. METHODS: In this study, we examined precursors of marijuana use in a sample of 1023 Dutch early adolescents (aged 11-14 at Time 1) who were never marijuana user at baseline, by applying a 3-wave longitudinal design. The theory of planned behavior (TPB) was used as a theoretical framework and posits that marijuana-specific cognitions (i.e., positive and negative expectancies, evaluative attitude, social approval, and self-efficacy) are antecedents of marijuana use and that this relationship is mediated by the intention to start using marijuana. RESULTS: In accordance with these premises, our results indicated that evaluative attitude, social approval, and self-efficacy at Time 1 are related to marijuana use at Time 3 (20 months follow-up) via the intention to start using marijuana at Time 2 (8 months follow-up). More specifically, the structural equation models showed that more positive marijuana attitudes, more approval from the social environment, and lower self-efficacy were related to marijuana use initiation through a stronger intention to start using marijuana. CONCLUSION: This outcome is important for prevention efforts in that our results underline the importance of weakening adolescents' positive attitudes toward marijuana, decrease social approval of marijuana use, and stimulating the development of early adolescents' refusal skills with respect to marijuana use. PMID- 22056218 TI - Protection by physical activity against deleterious effect of smoking on carotid intima-media thickness in young Japanese. AB - BACKGROUND: The hazardous effects of smoking and the favorable influence of physical activity on the progression of atherosclerosis have been well studied, but little is known about the interactions of these 2 factors. METHODS: A total of 1090 subjects who were screened for brain disease (at annual medical checkups) between April 2007 and March 2008 were studied to clarify the effects of smoking on maximum carotid intima-media thickness (IMT) in patients with different grades of physical activity. Univariate and multivariate analyses were performed to investigate relationships between maximum IMT and independent variables, such as smoking status, age, gender, coexisting disease, physical activity, alcohol drinking, family history, subjective symptoms, body mass index, systolic blood pressure, diastolic blood pressure, blood sugar, total cholesterol, high-density lipoprotein cholesterol, and triglycerides. RESULTS: Univariate analysis revealed only the low physical activity group to have a significant relationship between smoking and maximum IMT. When the subjects were divided into 3 age groups (<=49, 50-59, and <=60 years of age, respectively), the same association was noted for high and moderate physical activity groups <=49 years of age. Multivariate analysis further revealed smoking status to be a significant predictor of maximum IMT in the young low and moderate activity groups. CONCLUSIONS: In physically inactive young people, smoking might have detrimental effects on maximum IMT, while high physical activity may be protective. PMID- 22056219 TI - Lesion size and behavioral deficits after endothelin-1-induced ischemia are not dependent on time of day. AB - BACKGROUND: The occurrence of stroke exhibits a strong circadian pattern with a peak in the morning hours after waking. The factors that influence this pattern of stroke prevalence may confer varying degrees of neuroprotection and therefore influence stroke severity. This question is difficult to address in clinical cases because of the variability in the location and duration of the ischemic event. METHODS: The purpose of this study was to determine if time of day affected the severity of stroke targeting the motor cortex in rats. Strokes were produced using topical application of the vasoconstrictor endothelin-1 to motor cortex of unanesthetized animals at 2 time points: early day and early night. Behavioral deficits were measured using reaching, cylinder, and horizontal ladder tasks, and the volume of the lesion was quantified. RESULTS: Behavior on reaching and horizontal ladder tasks were both severely impaired by endothelin-1 treatment compared to vehicle-treated animals, but deficits did not differ according to time of treatment. Similarly, while endothelin-1 produced larger lesions of the motor cortex than did vehicle treatment, the size of the lesion did not differ according to time of treatment. CONCLUSIONS: These results suggest that while many factors under circadian control can influence the prevalence of stroke, the magnitude of lesion and behavioral deficit resulting from an ischemic event may not be influenced by time of day. PMID- 22056220 TI - The practice of carotid revascularization in a large metropolitan population. AB - Carotid endartectomy (CEA) and carotid artery stenting (CAS) reduce the risk of stroke when performed with acceptable perioperative morbidity and mortality. Studies from the 1980s in the greater Cincinnati/northern Kentucky population showed that perioperative risk after CEA exceeded the recommended boundaries of 3.0% for asymptomatic stenosis and 6.0% for symptomatic stenosis. We investigated the indications and outcomes for CEA and CAS in the same population during 2005. We identified all residents of the greater Cincinnati/northern Kentucky region who underwent CEA or CAS at any local hospital during 2005. Identified cases of transient ischemic attack or stroke occurring before or after CEA or CAS were abstracted by study nurses and reviewed by a study physician. The main outcome of interest was 30-day risk of stroke or death after CEA or CAS. Events were analyzed using Kaplan-Meier statistics. Among approximately 1.3 million greater Cincinnati/northern Kentucky residents, 525 CEAs were performed, 343 (65%) for asymptomatic stenosis and 182 (35%) for symptomatic stenosis. There were 43 CAS procedures, 23 (53%) for asymptomatic stenosis and 20 (47%) for symptomatic stenosis. The 30-day perioperative risk of stroke or death after CEA was 3.3% (95% confidence interval [CI], 1.8%-5.9%) for asymptomatic stenosis and 6.3% (95% CI, 3.5%-11.1%) for symptomatic stenosis. The 30-day perioperative risk of stroke or death after CAS was 4.6% (95% CI, 0.7%-28.1%) for asymptomatic stenosis and 21.1% (95% CI, 8.5%-46.8%) for symptomatic stenosis. Point estimates for perioperative risk after CEA were improved from previous studies but remained above the recommended benchmarks. The number of CAS procedures was low, but the perioperative risk was significant. PMID- 22056221 TI - Influence of experimental subarachnoid hemorrhage on nicotine-induced contraction of the rat basilar artery in relation to nicotinic acetylcholine receptors, calcium, and potassium channels. AB - BACKGROUND: Cigarette smoking is associated with symptomatic vasospasm after subarachnoid hemorrhage (SAH). METHODS: Rat basilar arteries of a normal group and SAH groups (1 hour, 2 days, and 1 week) were removed from the brain and cut into spiral preparations. RESULTS: A central nervous system (CNS) nicotinic acetylcholine receptor (nAChR) and autonomic ganglionic nAChR antagonist (mecamylamine) and skeletal muscle nAChR antagonist (gallamine) concentration dependently attenuated the nicotine-induced contraction. An autonomic ganglionic nAChR antagonist (hexamethonium) did not affect nicotine-induced contractions in normal rats or rats with SAH. The various nAChR antagonists showed no significant differences in their effects between normal and SAH (1 hour, 2 days, and 1 week) rats. An L-type Ca(2+) channel antagonist (nifedipine) attenuated the nicotine induced contraction in a concentration dependent manner. Inhibition by nifedipine was significantly enhanced in the 1-hour and 2-day SAH groups compared with normal and 1-week SAH groups. Levcromakalim showed a greater attenuation of nicotine-induced contraction in SAH (1 hour, 2 days, and 1 week) than in normal rats. CONCLUSIONS: Nicotine-induced contraction of the rat basilar artery involved the CNS nAChR subfamily, skeletal muscle nAChR subfamily, and L-type Ca(2+) channel pathways. SAH did not affect any of the subfamilies of nAChR, but the Ca(2+) channel was reduced and the adenosine triphosphate-sensitive K(+) channel was enhanced by SAH. PMID- 22056222 TI - The impact of early life permethrin exposure on development of neurodegeneration in adulthood. AB - Early life environmental exposure to pesticides could play a critical role in the onset of age-related diseases. The present study aims to evaluate in brain, plasma and leukocytes of 300 day-old rats, the effect of a low dose of the insecticide permethrin administered during early life (1/50 LD(50), from 6th to 21st day of life). The outcomes show that Nurr1, mRNA and protein expression, as well as calcium and NO levels are decreased in striatum. Moreover, the pesticide induces an imbalance in glutamate, calcium and NO in hippocampus. Low calcium concentrations in leukocytes and in plasma were observed, while increased NO and decreased SOD plasma levels were measured. The results suggest that permethrin intake at a dose close to the NOAEL (25 mg/kg) during the perinatal period can interact with Nurr1 by reducing its expression on striatum nucleus. Consequently, the maintenance of dopaminergic neurons as well as Nurr1 inhibitory effect on the production of proinflammatory mediators fails. The changes in biological markers found in our animal model could represent the basis to study neurodegenerative diseases whose development depends on individual gene signature and life style. PMID- 22056223 TI - Assessment of health literacy and numeracy among Spanish-Speaking parents of young children: validation of the Spanish Parental Health Literacy Activities Test (PHLAT Spanish). AB - OBJECTIVE: To assess the health literacy and numeracy skills of Spanish-speaking parents of young children and to validate a new Spanish language health literacy assessment for parents, the Spanish Parental Health Literacy Activities Test (PHLAT Spanish). METHODS: Cross-sectional study of Spanish-speaking caregivers of young children (<30 months) enrolled at primary care clinics in 4 academic medical centers. Caregivers were administered the 10-item PHLAT in addition to validated tests of health literacy (S-TOFHLA) and numeracy (WRAT-3 Arithmetic). Psychometric analysis was used to examine item characteristics of the PHLAT-10 Spanish, to assess its correlation with sociodemographics and performance on literacy/numeracy assessments, and to generate a shorter 8-item scale (PHLAT-8). RESULTS: Of 176 caregivers, 77% had adequate health literacy (S-TOFHLA), whereas only 0.6% had 9th grade or greater numeracy skills. Mean PHLAT-10 score was 41.6% (SD 21.1). Fewer than one-half (45.5%) were able to read a liquid antibiotic prescription label and demonstrate how much medication to administer within an oral syringe. Less than one-third (31.8%) were able to interpret a food label to determine whether it met WIC (Special supplemental nutrition program for Women, Infants, and Children) guidelines. Greater PHLAT-10 score was associated with greater years of education (r = 0.49), S-TOFHLA (r = 0.53), and WRAT-3 (r = 0.55) scores (P < .001). Internal reliability was good (Kuder-Richardson coefficient of reliability; KR-20 = 0.61). An 8-item scale was highly correlated with the full 10-item scale (r = 0.97, P < .001), with comparable internal reliability (KR-20 = 0.64). CONCLUSIONS: Many Spanish-speaking parents have difficulty performing health-related literacy and numeracy tasks. The Spanish PHLAT demonstrates good psychometric characteristics and may be useful for identifying parents who would benefit from receiving low-literacy child health information. PMID- 22056224 TI - Validity of faculty and resident global assessment of medical students' clinical knowledge during their pediatrics clerkship. AB - OBJECTIVE: Medical knowledge is one of six core competencies in medicine. Medical student assessments should be valid and reliable. We assessed the relationship between faculty and resident global assessment of pediatric medical student knowledge and performance on a standardized test in medical knowledge. METHODS: Retrospective cross-sectional study of medical students on a pediatric clerkship in academic year 2008-2009 at one academic health center. Faculty and residents rated students' clinical knowledge on a 5-point Likert scale. The inter-rater reliability of clinical knowledge ratings was assessed by calculating the intra class correlation coefficient (ICC) for residents' ratings, faculty ratings, and both rating types combined. Convergent validity between clinical knowledge ratings and scores on the National Board of Medical Examiners (NBME) clinical subject examination in pediatrics was assessed with Pearson product moment correlation correction and the coefficient of the determination. RESULTS: There was moderate agreement for global clinical knowledge ratings by faculty and moderate agreement for ratings by residents. The agreement was also moderate when faculty and resident ratings were combined. Global ratings of clinical knowledge had high convergent validity with pediatric examination scores when students were rated by both residents and faculty. CONCLUSIONS: Our findings provide evidence for convergent validity of global assessment of medical students' clinical knowledge with NBME subject examination scores in pediatrics. PMID- 22056225 TI - Upregulation of fibronectin and the alpha5beta1 and alphavbeta3 integrins on blood vessels within the cerebral ischemic penumbra. AB - Following focal cerebral ischemia, blood vessels in the ischemic border, or penumbra, launch an angiogenic response. In light of the critical role for fibronectin in angiogenesis, and the observation that fibronectin and its integrin receptors are strongly upregulated on angiogenic vessels in the hypoxic CNS, the aim of this study was to establish whether angiogenic vessels in the ischemic CNS also show this response. Focal cerebral ischemia was established in C57/Bl6 mice by middle cerebral artery occlusion (MCA:O), and brain tissue analyzed 7 days following re-perfusion, a time at which angiogenesis is ongoing. Within the ischemic core, immunofluorescent (IF) studies demonstrated vascular expression of MECA-32, a marker of leaky cerebral vessels, and vascular breakdown, defined by loss of staining for the endothelial marker, CD31, and the vascular adhesion molecules, laminin, dystroglycan and alpha6 integrin. Within the ischemic penumbra, dual-IF with CD31 and Ki67 revealed the presence of proliferating endothelial cells, indicating ongoing angiogenesis. Significantly, vessels in the ischemic penumbra showed strong upregulation of fibronectin and the fibronectin receptors, alpha5beta1 and alphavbeta3 integrins. Taken together with our recent finding that the alpha5beta1 integrin plays an important role in promoting cerebral angiogenesis in response to hypoxia, these results suggest that stimulation of the fibronectin-alpha5beta1 integrin signaling pathway may provide a novel approach to amplifying the intrinsic angiogenic response to cerebral ischemia. PMID- 22056226 TI - Negative predictive value of positron emission tomography and computed tomography for stage T1-2N0 non-small-cell lung cancer: a meta-analysis. AB - BACKGROUND: Nodal staging of non-small-cell lung cancer (NSCLC) is crucial in evaluation of prognosis and determination of therapeutic strategy. This study aimed to determine the negative predictive value (NPV) of combined positron emission tomography and computed tomography (PET-CT) in patients with stage I (T1 2N0) NSCLC and to investigate the possible risk factors for occult nodal disease. METHODS: Studies investigating the performance of PET in conjunction with CT in the nodal staging of stage I NSCLC were identified in the MEDLINE database. The initiative of standards for reporting of diagnostic accuracy (STARD) was used to ensure study quality. Pathologic assessments through mediastinoscopy or thoracotomy were required as the reference standard for evaluation of PET-CT accuracy. Stata-based meta-analysis was applied to calculate the individual and pooled NPVs. RESULTS: Ten studies with a total of 1122 patients with stage I (T1 2N0) NSCLC were eligible for analysis. The NPVs of combined PET and CT for mediastinal metastases were 0.94 in T1 disease and 0.89 in T2 disease. Including both T1 disease and T2 disease, the NPVs were 0.93 for mediastinal metastases and 0.87 for overall nodal metastases. Adenocarcinoma histology type (risk ratio [RR], 2.72) and high fluorine-18 (18F) fluorodeoxyglucose (FDG) uptake in the primary lesion were associated with greater risk of occult nodal metastases. CONCLUSIONS: Although overall occult nodal metastases in clinical stage T1-2N0 NSCLC is not infrequent, combined PET and CT provide a favorable NPV for mediastinal metastases in T1N0 NSCLC, suggesting a low yield from routine invasive staging procedures for this subgroup of patients. PMID- 22056227 TI - [Boost for patient safety with the centre agreement program]. AB - OBJECTIVE: To identify and define a minimum and standard set of safety objectives in the Centre Agreement Program (CAP) of the Community of Madrid, the introduction of which has led to improved follow-up and an improvement in quality of care and patient safety in Primary Care. MATERIAL AND METHODS: The key element is the Centre Agreement Program developed with the EFQM model as a reference. Methodologically, this project has followed the steps set out in the PDCA cycle., Standardised safety objectives were included in the CAP during the planning phase. Indicators have been monitored by the e-SOAP application. RESULTS: We have identified 12 safety goals and 21 indicators. All the criteria of the model included some safety objectives. We highlight the following results: in the criteria relating to processes, the program cover of patients who were on several medications was 59.22%, a bio-alcohol solution was used in 93% of health facilities, 89% of Health Centres had performed a control and maintenance of vital emergency equipment. As regards communication, 1096 medication errors were notified throughout the Community of Madrid. There were 239 adverse reactions to medication and 1945 safety incidents were reported. In criterion 6, 66.22% of INR determinations were within range. There were 19.46 defined daily doses (DDD) for women of 45-65 years, and 16.9 DDD of neuroleptics in the elderly population. The indicator related to minimising drugs considered inappropriate in the elderly (Beers) was 11.9%. An average of 1.19 safety measures were adopted per Centre. For Criterion 7, 14.44% of professionals had been trained in quality and patient safety. By implementing e-SOAP, Health Centres can know their results in order to implement improvements. In addition, improvements have been set up in the 2010 CAP. CONCLUSIONS: With the development of the CAP using the EFQM model as a benchmark, safety indicators have been implemented and monitored systematically in the Health Centres of the Community of Madrid. Best practices that ensure patient safety have been extended and we have begun to evaluate the impact of the health care provided in Primary Care with the measurement of indicators that the scientific evidence reveals affect patient safety. PMID- 22056228 TI - [A genetically confirmed CMT1A mimicking relapsing CIDP]. PMID- 22056229 TI - Stenting of an apparently symptomatic carotid stenosis. PMID- 22056230 TI - Pro-inflammatory cytokines are elevated in adolescent females with emotional disorders not treated with SSRIs. AB - BACKGROUND: Adults with major depressive disorder (MDD) show elevated levels of IL-6 and TNF-alpha. Studies of adolescents with MDD or anxiety disorders (AD) are few and present conflicting results. METHODS: We studied plasma cytokines in a clinical sample of adolescent females with MDD and/or clinical AD (n=60, mean age 16.8 years), compared to healthy controls (n=44; mean age 16.5 years). RESULTS: The clinical sample showed significantly higher values of IL-2 (Z=-4.09, p>0.0001), IL1-beta (Z=-2.40, p<0.05) and IL-10 (Z=-2.38, p<0.05) as compared to controls. The subgroup of the clinical sample not treated with SSRIs had a significant difference of IL-6 (Z=-2.26, p<0.05) in addition to the difference of IL-2 and IL1-beta, but showed no difference of IL-10 as compared to the controls. SSRI treatment was related to IL-6, explaining 26% of the variance in the clinical sample after controlling for BMI and symptom severity. In the clinical sample, levels of IL-6 and IFN-gamma were positively correlated with self assessed symptoms of anxiety and/or depression (corr.coeff 0.35 resp 0.40 at p<0.05). LIMITATIONS: The cross-sectional design does not allow for conclusions on causality. The sample sizes were relatively small and a large drop-out in the clinical sample may have influenced the representativity. DISCUSSION: The study suggests that pro-inflammatory cytokines are part of the pathophysiology of emotional disorders in adolescent females and that SSRIs have anti-inflammatory properties. The findings prompt further studies on the specific mechanisms involved and may contribute to the development of more effective treatment and prevention. PMID- 22056231 TI - A high-throughput screen to identify novel calcineurin inhibitors. AB - Calcineurin is a eukaryotic protein phosphatase important for many signalling and developmental processes in cells. Inhibitors of this enzyme are used clinically and there is interest in identifying novel inhibitors for therapeutic applications. This report describes a high-throughput assay that can be used to screen natural or chemical libraries of compounds to identify new calcineurin inhibitors. The microtitre plate assay is based on a yeast reporter strain and was validated with known inhibitors and tested in a pilot screen of bacterial extracts. PMID- 22056232 TI - Production and characterization of a novel monoclonal antibody against Vibrio parahaemolyticus F0F1 ATP synthase's delta subunit and its application for rapid identification of the pathogen. AB - We raised monoclonal antibodies (MAbs) against Vibrio parahaemolyticus cell extracts. One of the MAbs, designated MAb-VP34, reacted in enzyme-linked immunosorbent assays (ELISAs) with 140 V. parahaemolyticus strains, regardless of serotype or origin. MAb-VP34 did not detectably react with 96 strains belonging to 27 other Vibrio species (except for Vibrio natriegens) or with 29 non-Vibrio species. These results show that MAb-VP34 is highly specific for V. parahaemolyticus. Western blotting and mass spectrometry analyses revealed that MAb-VP34 recognized V. parahaemolyticus F(0)F(1) ATP synthase's delta subunit. Using MAb-VP34, a rapid and simple immunodot blotting assay (VP-Dot) was developed to determine whether bacterial colonies growing on selective agar, represented V. parahaemolyticus. To evaluate VP-Dot, 20 V. parahaemolyticus strains and 19 non-related strains were tested. The results indicated that VP-Dot is a reliable tool for identification of V. parahaemolyticus colonies. The simple VP-Dot procedure took 40min, indicating that the MAb-VP34 based immunological method will greatly reduce labor, time, and costs required to verify V. parahaemolyticus colonies as compared with the conventional biochemical test. PMID- 22056233 TI - Nonlinear electrophoresis for purification of soil DNA for metagenomics. AB - Purification of microbial DNA from soil is challenging due to the co-extraction of humic acids and associated phenolic compounds that inhibit subsequent cloning, amplification or sequencing. Removal of these contaminants is critical for the success of metagenomic library construction and high-throughput sequencing of extracted DNA. Using three different composite soil samples, we compared a novel DNA purification technique using nonlinear electrophoresis on the synchronous coefficient of drag alteration (SCODA) instrument with alternate purification methods such as direct current (DC) agarose gel electrophoresis followed by gel filtration or anion exchange chromatography, Wizard DNA Clean-Up System, and the PowerSoil DNA Isolation kit. Both nonlinear and DC electrophoresis were effective at retrieving high-molecular weight DNA with high purity, suitable for construction of large-insert libraries. The PowerSoil DNA Isolation kit and the nonlinear electrophoresis had high recovery of high purity DNA suitable for sequencing purposes. All methods demonstrated high consistency in the bacterial community profiles generated from the DNA extracts. Nonlinear electrophoresis using the SCODA instrument was the ideal methodology for the preparation of soil DNA samples suitable for both high-throughput sequencing and large-insert cloning applications. PMID- 22056234 TI - Genetics of maximally attained lung function: a role for leptin? AB - OBJECTIVES: To estimate the heritabilities of maximally attained lung function in young adult twins, and to examine whether circulating leptin, leptin (LEP) and leptin receptor (LEPR) gene polymorphisms are associated with maximally attained lung function. METHODS: Measures on forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) were available of 578 twins recruited from the East Flanders Prospective Twin Survey (165 monozygotic (MZ) and 73 dizygotic (DZ) complete pairs and 102 single twins). Twin model fitting and (genetic) association analyses were performed. RESULTS: Intra-pair correlations of FEV(1) and FVC did not differ significantly between MZ monochorionic and MZ dichorionic pairs. Heritability estimates of FEV(1) and FVC were 69% and 63%, respectively. The A allele of the LEP 19G>A SNP was significantly associated with a lower FEV(1) (p(Additive) = 0.01) and FVC (p(Dominant) = 0.047), while the LEPR K109R and Q223R SNPs showed no associations. Accounting for body mass index, serum leptin was negatively associated with FVC (p = 0.02) in men, but not in women. CONCLUSIONS: More than 60% of variation in maximally attained FEV(1) and FVC is explained by genetic factors. Moreover, these results suggest that leptin may be important in the determination of maximally attainable lung function. PMID- 22056235 TI - The influence of body weight on social network ties among adolescents. AB - Evidence of negative stereotypes, prejudice and discrimination towards obese individuals has been widely documented. However, the effect of a larger body size on social network ties or friendship formations is less well understood. In this paper, we explore the extent to which higher body weight results in social marginalization of adolescents. Using data from a nationally representative sample of adolescents, we estimate endogeneity-corrected models including school level fixed effects that account for bi-directionality and unobserved confounders to ascertain the effect of body weight on social network ties. We find that obese adolescents have fewer friends and are less socially integrated than their non obese counterparts. We also find that such penalties in friendship networks are present among whites but not African-Americans or Hispanics, with the largest effect among white females. These results are robust to common environmental influences at the school-level and to controls for preferences, risk attitudes, low self-esteem and objective measures of physical attractiveness. PMID- 22056236 TI - Age-related changes in gene expression of the growth hormone secretagogue and growth hormone-releasing hormone receptors in Holstein-Friesian cattle. AB - Growth hormone secretion from the anterior pituitary gland is controlled by interactions between three hormone receptors, between GHRH and GHRH receptor (GHRH-R), between ghrelin and growth hormone secretagogue receptor (GHS-R1a), and between somatostatin and somatostatin receptors in the hypothalamus and anterior pituitary gland. Ghrelin-GHS-R1a is involved in many important functions, including GH secretion and appetite. We investigated age-related changes in the expressions of GHS-R1a, GHS-R1b (the truncated-type receptor), and GHRH-R mRNAs by real-time reverse transcription-PCR using 16 tissues, leukocytes, oocytes, and cumulus cells in Holstein-Friesian cattle. The tissue samples were divided into three age classes: 1) 19 to 26 d of age (preweaning calves), 2) 2 mo to 6.5 mo of age (postweaning calves), and 3) 3.2 to 8.1 yr of age (cows). The GHS-R1a mRNA was highly (P < 0.05) expressed in the arcuate nucleus, pituitary gland, and liver compared with that of the other tissues in all age classes. Expression of GHS-R 1a mRNA in the arcuate nucleus of postweaning calves was > 10-fold greater (P < 0.01) than those of preweaning calves and cows, and its expression level was the greatest (P < 0.01) in all tissues examined in age group 2. GHS-R1a and GHRH R mRNA expressions in the pituitary gland of preweaning calves tended to be greater (P < 0.20 and P < 0.17, respectively) than those of postweaning calves and cows. GHS-R1b mRNA expression was detected in all tissues examined, and abundance was greater (P < 0.05) in the pancreas, pituitary gland, spleen, arcuate nucleus, adipose tissue, and leukocyte compared with that of the other tissues examined in age group 3. Interestingly, a relatively large animal-to animal variation was observed in pancreas GHS-R 1b mRNA expression. The GHRH-R mRNA was markedly increased (P < 0.01) in the pituitary gland in all age groups compared with that of the other tissues. GHRH-R mRNA abundance in the arcuate nucleus, pituitary gland, liver, spleen, adipose tissue, and heart of preweaning calves tended to be greater than those of postweaning calves and cows. The GHRH-R mRNA was not detected in the mammary gland and adipose tissue of nonlactating cows. PMID- 22056237 TI - Development and validation of a hydrophilic interaction chromatography-tandem mass spectrometry method with on-line polar extraction for the analysis of urinary nucleosides. Potential application in clinical diagnosis. AB - The present paper describes the development, validation and application of a quantitative method for the determination of endogenous nucleosides and nucleobases in urine based on the on-line coupling of a solid-phase extraction step with hydrophilic interaction chromatography-tandem mass spectrometry. The method combines the use of a highly polar restricted-access material (RAM), based on an N-vinylacetamide copolymer, for efficient analyte extraction and matrix removal, with separation by zwitterionic hydrophilic interaction chromatography (ZIC-HILIC), that revealed a satisfactory retention of the polar analytes studied. Detection using a triple quadrupole analyser allowed reliable identification and high-sensitivity quantitation of the target compounds. The on line configuration developed, RAM-ZIC-HILIC-MS/MS, provides a convenient approach to automate the application to urine analysis, with minimum sample manipulation. The whole method was validated according to European Legislation for bioanalytical methods. The validation steps included the verification of matrix effects, calibration curve, precision, accuracy, selectivity, stability and carry over in real samples. The results of the validation process revealed that the proposed method is suitable for the reliable determination of nucleosides and nucleobases in human urine, showing limits of detection from 0.1 to 1.3 ng mL( 1). The application to clinical samples was also checked; the results obtained in analyses of urine samples from healthy volunteers and cancer patients using Principal Component Analysis, Hierarchical Cluster Analysis and Soft Independent Modeling of Class Analogy are also shown. PMID- 22056238 TI - Theoretical and practical aspects in the separation of large biomolecules. PMID- 22056239 TI - Trace level analysis of corky off-flavor compounds: development of a new analytical method based on solid phase extraction and analysis by multidimensional gas chromatography with mass spectrometric detection. AB - This work describes the development of a trace level (<1 ngL(-1)) analysis of haloanisoles in complex wine matrix. The suggested method involves sample preparation based on solid phase extraction, a clean-up to remove acidic compounds, concentration of the haloanisole fraction and large volume on-column injection into a multidimensional GC-MS system. Mass spectrometric detection in the selected ion mode allowed reliable quantification of 2,4,6-trichloroanisole (TCA) or 2,4,6-tribromoanisole (TBA), via their highly deuterated ([(2)H5]) isotopologues as internal standards (stable isotope dilution analysis; SIDA), which had prior been synthesized in house. The development of this new method had become necessary, as a one-dimensional HS-SPME-GC-ECD method, routinely applied for analysis of TCA in cork soaks, had to be extended for TeCA and TBA determination, but failed due to co-elutions within wine matrices. The newly developed SPE//MDGC-MS method provided detection limits well below olfactory thresholds of the analytes with 0.05 ngL(-1) (LOD), 0.19 ngL(-1) (LOQ) for TCA, 0.06 ngL(-1) (LOD), 0.21 ngL(-1) (LOQ) for TeCA, and 0.09 ngL(-1) (LOD), 0.34 ngL(-1) (LOQ) for TBA. PMID- 22056240 TI - Determination of pharmaceutically related compounds by suppressed ion chromatography: I. Effects of organic solvent on suppressor performance. AB - This overall study aims to investigate gradient elution ion-exchange chromatography of pharmaceutically relevant compounds using universal nebulisation detectors, such as evaporative light scattering detection (ELSD). Addition of organic solvents to the eluent is necessary to minimise hydrophobic adsorption on the polymeric stationary phase and improve solubility of analytes. It is also necessary to de-salt the eluent prior to detection, and in this work, ion chromatography suppressors were used for this step. Such suppressors have been designed for aqueous eluents, so the purpose of the present study was to investigate the effects of methanol and acetonitrile on suppressor performance. Chemical and electrolytic suppressors were evaluated for baseline drift, noise and efficiency of suppression using aqueous/organic eluents containing up to 40% (v/v) methanol or acetonitrile. Chemical suppression of aqueous/organic eluents showed minimal noise levels, uniform low baseline and low gradient drift. Electrolytic suppression gave good performance, but with higher baseline conductivity levels and baseline drift than chemical suppression. The elevated baseline was found not to be caused by incomplete suppression of the eluent, but was attributed to chemical reactions involving the organic solvents and facilitated by high electric currents and heat generation. It was demonstrated that suppressed ion-exchange separation using a complex KOH elution profile could be coupled with ELSD, with the suppressor effectively de-salting the eluent, producing a stable baseline. Finally, complementary separation selectivity was demonstrated using a set of pharmaceutically related organic acids separated by reversed-phase and ion-exchange methods. PMID- 22056241 TI - Rapid quantification of pharmaceuticals and pesticides in passive samplers using ultra high performance liquid chromatography coupled to high resolution mass spectrometry. AB - The presence of both pharmaceuticals and pesticides in the aquatic environment has become a well-known environmental issue during the last decade. An increasing demand however still exists for sensitive and reliable monitoring tools for these rather polar contaminants in the marine environment. In recent years, the great potential of passive samplers or equilibrium based sampling techniques for evaluation of the fate of these contaminants has been shown in literature. Therefore, we developed a new analytical method for the quantification of a high number of pharmaceuticals and pesticides in passive sampling devices. The analytical procedure consisted of extraction using 1:1 methanol/acetonitrile followed by detection with ultra-high performance liquid chromatography coupled to high resolution and high mass accuracy Orbitrap mass spectrometry. Validation of the analytical method resulted in limits of quantification and recoveries ranging between 0.2 and 20 ng per sampler sheet and between 87.9 and 105.2%, respectively. Determination of the sampler-water partition coefficients of all compounds demonstrated that several pharmaceuticals and most pesticides exert a high affinity for the polydimethylsiloxane passive samplers. Finally, the developed analytical methods were used to measure the time-weighted average (TWA) concentrations of the targeted pollutants in passive samplers, deployed at eight stations in the Belgian coastal zone. Propranolol, carbamazepine and seven pesticides were found to be very abundant in the passive samplers. These obtained long-term and large-scale TWA concentrations will contribute in assessing the environmental and human health risk of these emerging pollutants. PMID- 22056242 TI - Frontal affinity chromatography with MS detection of the ligand binding domain of PPARgamma receptor: ligand affinity screening and stereoselective ligand macromolecule interaction. AB - In this study we report the development of new chromatographic tools for binding studies based on the gamma isoform ligand binding domain (LBD) of peroxisome proliferator-activated receptor (PPARgamma) belonging to the nuclear receptor superfamily of ligand-activated transcription factors. PPARgamma subtype plays important roles in the functions of adipocytes, muscles, and macrophages with a direct impact on type 2 diabetes, dyslipidemia, atherosclerosis, and cardiovascular disease. In order to set up a suitable immobilization chemistry, the LBD of PPARgamma receptor was first covalently immobilized onto the surface of aminopropyl silica particles to create a PPARgamma-Silica column for zonal elution experiments and then onto the surface of open tubular (OT) capillaries to create PPARgamma-OT capillaries following different immobilization conditions. The capillaries were used in frontal affinity chromatography coupled to mass spectrometry (FAC-MS) experiments to determine the relative binding affinities of a series of chiral fibrates. The relative affinity orders obtained for these derivatives were consistent with the EC(50) values reported in literature. The optimized PPARgamma-OT capillary was validated by determining the K(d) values of two selected compounds. Known the role of stereoselectivity in the binding of chiral fibrates, for the first time a detailed study was carried out by analysing two enantioselective couples on the LBD-PPARgamma capillary by FAC and a characteristic two-stairs frontal profile was derived as the result of the two saturation events. All the obtained data indicate that the immobilized form of PPARgamma-LBD retained the ability to specifically bind ligands. PMID- 22056243 TI - Curing APL through PML/RARA degradation by As2O3. AB - Acute promyelocytic leukemia (APL) is a hematological malignancy driven by the PML/RARA oncogene. The prognosis for patients with APL was revolutionized by two treatments: retinoic acid (RA) and As(2)O(3) (arsenic trioxide). These were both shown a posteriori to target PML/RARA, explaining their exquisite specificity for APL. Arsenic, as a single agent, cures up to 70% of patients, whereas APL patients treated with the combination of RA and As(2)O(3) reach a stunning 90% cure rate. Recent physiopathological models highlight the key role of RA- and As(2)O(3)-triggered PML/RARA degradation, and the molecular mechanisms underlying As(2)O(3)-induced PML/RARA degradation have been recently clarified. As discussed below, arsenic binding, oxidation, sumoylation on PML nuclear bodies, and RNF4 mediated ubiquitination all contribute to the As(2)O(3)-triggered catabolism of PML/RARA. PMID- 22056244 TI - A free-floating left atrial mass. PMID- 22056245 TI - Tilting the AXIS towards therapeutic limits in renal cancer. PMID- 22056246 TI - Medical complications associated with earthquakes. AB - Major earthquakes are some of the most devastating natural disasters. The epidemiology of earthquake-related injuries and mortality is unique for these disasters. Because earthquakes frequently affect populous urban areas with poor structural standards, they often result in high death rates and mass casualties with many traumatic injuries. These injuries are highly mechanical and often multisystem, requiring intensive curative medical and surgical care at a time when the local and regional medical response capacities have been at least partly disrupted. Many patients surviving blunt and penetrating trauma and crush injuries have subsequent complications that lead to additional morbidity and mortality. Here, we review and summarise earthquake-induced injuries and medical complications affecting major organ systems. PMID- 22056247 TI - Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. AB - BACKGROUND: The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis. So far, no phase 3 randomised trials comparing the effectiveness of one targeted agent against another have been reported. We did a randomised phase 3 study comparing axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor (VEGF) receptors, with sorafenib, an approved VEGF receptor inhibitor, as second-line therapy in patients with metastatic renal cell cancer. METHODS: We included patients coming from 175 sites (hospitals and outpatient clinics) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or cytokines. Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then randomly assigned (1:1) to either axitinib (5 mg twice daily) or sorafenib (400 mg twice daily). Axitinib dose increases to 7 mg and then to 10 mg, twice daily, were allowed for those patients without hypertension or adverse reactions above grade 2. Participants were not masked to study treatment. The primary endpoint was progression-free survival (PFS) and was assessed by a masked, independent radiology review and analysed by intention to treat. This trial was registered on ClinicalTrials.gov, number NCT00678392. FINDINGS: A total of 723 patients were enrolled and randomly assigned to receive axitinib (n=361) or sorafenib (n=362). The median PFS was 6.7 months with axitinib compared to 4.7 months with sorafenib (hazard ratio 0.665; 95% CI 0.544-0.812; one-sided p<0.0001). Treatment was discontinued because of toxic effects in 14 (4%) of 359 patients treated with axitinib and 29 (8%) of 355 patients treated with sorafenib. The most common adverse events were diarrhoea, hypertension, and fatigue in the axitinib arm, and diarrhoea, palmar-plantar erythrodysaesthesia, and alopecia in the sorafenib arm. INTERPRETATION: Axitinib resulted in significantly longer PFS compared with sorafenib. Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma. FUNDING: Pfizer Inc. PMID- 22056248 TI - Neonatal hypoxia-ischemia induces sex-related changes in rat brain mitochondria. AB - The effects of neonatal hypoxia-ischemia (HI) on energy metabolism in male and female rats were investigated, testing the hypothesis that HI-induced brain mitochondrial dysfunction could present in a dimorphic pattern. Impairment in electron transport chain complex activities at 2 and 18 h after HI was observed in cortex and hippocampus in rats of both sexes, with females presenting an overall activity higher than that of males. Females also showed loss of mitochondrial mass and membrane potential 18 h after HI, while males were only slightly affected. These findings suggest a dimorphism in mitochondrial dysfunction and provide information that may lead to new neuroprotection strategies. PMID- 22056249 TI - Long-term follow-up of type II endoleak embolization reveals the need for close surveillance. AB - OBJECTIVE: Aneurysm growth after endovascular aneurysm repair (EVAR) in patients with type II endoleak is associated with adverse outcomes. This study evaluated the long-term success of embolization of type II endoleaks in preventing aneurysm sac growth. METHODS: We retrospectively reviewed outcomes of patients who underwent infrarenal EVAR who were treated for a type II endoleak between 2000 and 2008. Computed tomography scans were evaluated for aneurysm sac growth or shrinkage from the time of treatment of the endoleak. The embolization material used, graft type, target vessel embolized, and comorbidities were evaluated for their association with sac growth or shrinkage. RESULTS: Ninety-five patients underwent 140 embolization procedures. The mean time from EVAR to embolization was 26.1 +/- 22.2 months, and the average increase in size of the aneurysm sac from EVAR to treatment was 0.7 * 0.5 cm. Patients underwent an average of 1.6 +/- 0.8 embolization procedures after EVAR. Thirteen patients underwent initial simultaneous embolization of two targets. Embolization was with glue (61%), coils (29%), glue and coils (7%), and Gelfoam (3%; Pfizer Inc, New York, NY). No abdominal aortic aneurysms (AAA) ruptured. Eight patients (8.4%) underwent graft explant and open repair; 19 (20%) required two or more embolization procedures. There was no difference in the target vessel treated or the treatment used in halting sac expansion (>5 mm). Coil embolization alone resulted in more second procedures. The 5-year cumulative survival was 65% (95% confidence interval [CI], 52%-77%), freedom from explant was 89% (95% CI, 81%-97%), freedom from second embolization was 76% (95% CI, 66%-86%), and freedom from sac expansion >5 mm was 44% (95% CI 30%-50%). Univariable analysis identified continued tobacco use (hazard ratio [HR], 2.30; 95% CI, 1.02-5.13; P = .04) was associated with continued sac expansion, and hyperlipidemia (HR, 9.64; 95% CI, 2.22-41.86) was associated with patients requiring a second embolization procedure. CONCLUSIONS: Embolization of type II endoleaks is successful early in preventing aneurysm sac growth and rupture after EVAR. However, a significant number of patients require more than one procedure, and at 5 years, many patients who underwent embolization of a type II endoleak continued to experience sac growth. Patients with hyperlipidemia who undergo coil embolization are more likely to require a second embolization procedure, and patients who smoke have a higher likelihood of AAA sac expansion after embolization. Continued long-term surveillance is necessary in this cohort of patients. PMID- 22056251 TI - Diabetes is not a predictor of outcome for carotid revascularization with stenting as it may be for carotid endarterectomy. AB - BACKGROUND: Diabetes is prevalent in most patients undergoing carotid revascularization and is suggested as a marker of poor outcome after carotid endarterectomy (CEA). Data on outcome of diabetic patients undergoing carotid artery stenting (CAS) are limited. The aim of this study was to investigate early and 6-year outcomes of diabetic patients undergoing carotid revascularization with CAS and CEA. METHODS: The database of patients undergoing carotid revascularization for primary carotid stenosis was queried from 2001 to 2009. Diabetic patients were defined as those with established diagnosis and/or receiving oral hypoglycemic or insulin therapy. Multivariate and Kaplan- Meier analyses, stratified by type of treatment, were performed on perioperative (30 days) and late outcomes. RESULTS: A total of 2196 procedures, 1116 by CEA and 1080 by CAS (29% female, mean age 71.3 years), were reviewed. Diabetes was prevalent in 630 (28.7%). Diabetic patients were younger (P < .0001) and frequently had hypertension (P = .018) or coronary disease (P = .019). Perioperative stroke/death rate was 2.7% (17/630) in diabetic patients vs 2.3% (36/1566) in nondiabetic, (P = .64); the rate was 3.4% in diabetic CEA group and 2.1% in diabetic CAS group (P = .46). At multivariate analyses, diabetes was a predictor of perioperative stroke/death in the CEA group (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.05-7.61; P = .04) but not in the CAS group (P = .72). Six-year survival was 76.0% in diabetics and 80.8% in nondiabetics (P = .15). Six-year late stroke estimates were 3.2% in diabetic and 4.6% in nondiabetic patients (P = .90). The 6-year risk of restenosis was similar (4.6% % vs 4.2%) in diabetic and nondiabetic patients (P = .56). Survival, late stroke, and restenosis rates between diabetics and nondiabetics were similar in CAS and CEA groups. CONCLUSIONS: Diabetic patients are not at greater risk of perioperative morbidity and mortality or late stroke after CAS, however, the perioperative risk can be higher after CEA. This may help in selecting the appropriate technique for carotid revascularization in patients best suited for the type of procedure. PMID- 22056252 TI - Preparation of parathion imprinted polymer beads and its applications in electrochemical sensing. AB - Parathion imprinted polymer beads were prepared by free radical polymerization using parathion as template, methacrylic acid as functional monomer, divinyl benzene as cross-linking reagent and 2,2'-azobis(isobutyronitrile) as initiator. The obtained molecularly imprinted beads were characterized with transmission electron micrograph. The rebinding properties of these imprinted beads towards parathion were studied by saturation binding experiments using ultraviolet/visible spectroscopy. Effects of the template, functional monomer, cross-linking reagent and initiator on selective adsorption of parathion were investigated. The high selectivity of the imprinted beads was successfully demonstrated by their selective adsorption of free parathion from an ethanol water (v/v=1:5) solution. In addition, the parathion imprinted beads were dispersed into dihexadecyl hydrogen phosphate solution at the concentration of 1.0 mg mL(-1). By coating this solution onto a glassy carbon electrode surface, a molecularly imprinted electrochemical sensor for parathion was obtained. The electrochemical sensor exhibited good selectivity and fast response to parathion. Under optimized experimental conditions, the peak currents were found linearly proportional to the parathion concentration in the range of 1.0*10(-7) mol L(-1) to 1.0*10(-5) mol L(-1) with a detection limit of 5.4*10(-8) mol L(-1) (S/N=3). The developed sensor was successfully employed for the determination of parathion in pear juice samples. PMID- 22056253 TI - Spectroscopic and microscopic characterization of biosensor surfaces with protein/amino-organosilane/silicon structure. AB - Composition and structure of biorecognition protein layers created on silicon substrates modified with amino-organosilanes determine the sensitivity and specificity of silicon based biosensing devices. In the present work, diverse spectroscopic and microscopic methods were applied to characterize model biosensor surfaces, formed on Si(3)N(4) or SiO(2) by modification with (3 aminopropyl)triethoxysilane, coating with rabbit gamma-globulins (IgGs) through physical adsorption, blocking with bovine serum albumin (BSA) and specific binding of an anti-rabbit IgG antibody. In addition, silanized substrates with directly adsorbed BSA or anti-rabbit IgG antibody were examined as reference surfaces. The protein/amino-organosilane/silicon structure of all surfaces was confirmed by X-ray photoelectron spectroscopy. Homogeneity of protein coverage was verified with near-field scanning optical microscope, working in reflection and fluorescence mode. Surface coverage with proteins was determined with angle resolved XPS using a previously established bilayer approach. Inner structure of protein layers was examined with atomic force microscopy. Vertical arrangement of carbon functional groups was revealed by high resolution ARXPS. Combined spectroscopic and microscopic data reveal the complex character of interactions with the immobilized IgG molecules during blocking with BSA and immunoreaction with anti-IgG antibody. Within experimental error, neither surface coverage nor lateral structural scales of protein layer (provided by Fourier and auto correlation analysis of topographic and phase images) increase during blocking procedure. On the other hand, coverage and all structural measures rise considerably after immunoreaction. In addition, it was found that polar functional groups orient towards substrate for all protein layers, independently of coverage, prior to and after both blocking and specific binding. PMID- 22056254 TI - Evaluation of copper-64-labeled somatostatin agonists and antagonist in SSTr2 transfected cell lines that are positive and negative for p53: implications for cancer therapy. AB - OBJECTIVES: Radiolabeled somatostatin analogs have become important agents for molecular imaging and targeted radiotherapy of somatostatin receptor-positive tumors. Here we determine the effect of the tumor suppressor protein, p53, on trafficking (64)Cu to tumor cell nuclei from DOTA vs. CB-TE2A-conjugated agonist Y3-TATE and the antagonist (64)Cu-CB-TE2A-sst2-ANT in cell lines that are positive or negative for p53. METHODS: Receptor binding, internalization, cyclic adenosine monophosphate (cAMP) and nuclear localization studies were performed with the somatostatin receptor subtype 2 (SSTr2) agonists, (64)Cu-CB-TE2A-Y3-TATE and (64)Cu-DOTA-Y3-TATE vs. antagonist, (64)Cu-CB-TE2A-sst2-ANT, in SSTr2 transfected p53 +/+ and -/- HCT116 colorectal carcinoma cells. RESULTS: The antagonist, (64)Cu-CB-TE2A-sst2-ANT, bound 8-9-fold more SSTr2 binding sites than did the (64)Cu-labeled agonists. (64)Cu-CB-TE2A-Y3-TATE was more efficiently internalized than (64)Cu-DOTA-Y3-TATE, while (64)Cu-CB-TE2A-sst2-ANT showed lower yet significant levels of internalization. CB-TE2A-Y3-TATE acted as a full agonist, inhibiting cAMP production, whereas CB-TE2A-sst2-ANT showed no inhibition of cAMP production. The (64)Cu from agonists (64)Cu-DOTA-Y3-TATE and (64)Cu-CB-TE2A-Y3-TATE showed greater nuclear localization at 24 h in p53 +/+ vs. -/- cells; however, there was no difference in the levels of (64)Cu from the antagonist based on p53 status. Surprisingly, the DOTA and CB-TE2A-conjugated agonists showed similar nuclear localization in the p53 +/+ and -/- cells, suggesting no difference in (64)Cu release from these chelators in the HCT116 cell lines. CONCLUSION: Based on these in vitro data, the agonist (64)Cu-CB-TE2A Y3-TATE demonstrates the most promise as an agent for targeted radiotherapy in p53 positive, SSTr2-positive tumors. PMID- 22056255 TI - [Lupus vulgaris caused by Mycobacterium bovis]. PMID- 22056256 TI - [Dermatology residency training: past, present, and future]. PMID- 22056257 TI - Omalizumab for the treatment of atopic dermatitis. AB - Atopy is almost always associated with an elevated immunoglobulin (Ig) E production. Omalizumab is a monoclonal anti-IgE antibody that is currently indicated for the treatment of cases of asthma that satisfy certain criteria. A number of studies have been published on the usefulness of omalizumab in the treatment of atopic dermatitis, and the results have been variable. We present our experience in the treatment of 9 patients with severe atopic dermatitis refractory to at least 2 systemic drugs. All patients reported a decrease in pruritus and an improvement in quality of life. Good control of the skin disease was achieved with omalizumab in monotherapy in 2 patients, and there was a slight improvement in the eczematous lesions in 4 patients. Those patients who also had asthma achieved good control of their respiratory symptoms and did not require additional therapy. Omalizumab is a well-tolerated and safe drug that can be useful for the treatment of severe atopic dermatitis refractory to other systemic therapies. This monoclonal anti-IgE antibody is a major therapeutic advance as it opens the door to the management of atopic dermatitis using systemic immunomodulating therapies. PMID- 22056258 TI - [Nail involvement in leprosy]. AB - Leprosy, a disease caused by Mycobacterium leprae, primarily affects the skin and nerves, but the nails are also involved in as many as 3 out of 4 patients .The factors that trigger nail changes in leprosy are numerous and include repeated trauma, neuropathy, vascular impairment, infections, lepra reactions, and the drugs used to manage the disease. The changes most often reported include subungual hematomas, onycholysis, onychauxis, onychogryphosis, pterygium unguis, and onychoheterotopia, most of which can be attributed to nerve damage and trauma. Furthermore, the acro-osteolysis that occurs in the advanced stages of the disease may present with brachyonychia, racquet nails, or even anonychia. Infections of the nail bed leading to paronychia and onychomycosis should also be taken into account in leprosy. Other typical changes include longitudinal striae, pitting, macrolunula, Terry nails, leukonychia, hapalonychia, and Beau lines. In this review, we describe the principal nail changes associated with leprosy. These changes, which are highly varied and diverse in origin, are in fact a reflection of the significant morbidity caused by M. leprae infection. PMID- 22056259 TI - [Vitiligo and morphea: autoimmune cutaneous side effects of interferon treatment]. PMID- 22056260 TI - [Abortive or minimal-growth hemangiomas. A review of 14 cases]. PMID- 22056261 TI - Cell growth inhibition and apoptotic effect of the rexinoid 6-OH-11-O hydroxyphenantrene on human osteosarcoma and mesenchymal stem cells. AB - Natural derivatives of vitamin A, including all-trans-retinoic acid (ATRA), commonly known as retinoids, currently produce favorable results in the treatment of many types of tumors. The rexinoid 6-OH-11-O-hydroxyphenantrene (IIF) is a synthetic derivative of ATRA. Previous in vitro and in vivo studies demonstrated that IIF is able to induce growth inhibition of various cancer cells and is a potent apoptosis-inducing agent with clinical potential. Osteosarcoma (OS) is the most common type of bone cancer, characterized by a rising aggressiveness. Recent evidences suggest that mesenchymal stem cells (MSC) may favour tumor growth and progression. Thus, it is important to investigate whether a compound with potential anti-tumoral properties such as IIF affects not only tumor cells but also MSC. The current study is an attempt to understand the mode of the potential cytotoxicity of IIF on OS cells and MSC. The response to IIF treatment of osteosarcoma SaOS-2, MG63, and U2OS cells and of bone marrow-derived MSC was the subject of investigation. The results showed that IIF significantly inhibited cell growth in OS cell lines and MSC in both a time- and dose-dependent manner, as evaluated by methylene blue assay. This was also associated with altered cell morphology and an increase in cell death with the involvement of apoptosis as demonstrated by NucleoCounter, Hoechst 33342 staining and FACS analysis. No cell death and apoptosis was found in U2OS cells. Analysis of cells treated with 20 and 40MUM IIF for 24h by western blot suggests the activation of initiator caspase 9, indicating the involvement of caspases in inducing apoptosis. Furthermore, IIF upregulated the expression of the pro-apoptotic protein Bax and downregulated the anti-apoptotic protein Bcl2. For the first time, our results collectively provide an evidence for cell growth inhibition and activation of apoptosis in human OS cells and MSC by IIF. These results confirm that IIF may be an effective compound for anticancer treatment, including that of OS. PMID- 22056262 TI - Solubilizing agents in nasal formulations and their effect on ciliary beat frequency. AB - The purpose of this study was to determine the concentration-dependent effect of selected solubilizers, used in common nasal drug formulations, on ciliary beat frequency (CBF) in human nasal epithelial cell cultures. CBF was measured by a high-speed digital imaging method. Excised ciliated human nasal epithelial cells were incubated for 60min with the solubilizers and determination of the half maximal inhibitory concentration (IC(50)), followed by a reversibility test. LDH test was performed on human nasal epithelial cells with the solubilizing agents. These were applied to nasal epithelial cells in IC(50) values. The following rank order in IC(50) values was obtained for the solubilizers: glycerol>propylene glycol>polyethylene glycol 300>N,N-dimethylacetamide>polyethylene glycol 400>ethanol>ethylendiamindihydrochloride>polyvinylpyrrolidon 25>polyvinylpyrrolidon 90. The highest reversibility of approximately 75% was shown by propylene glycol and polyethylene glycol 300 at a concentration of 30% (v/v). Results from the LDH test showed that N,N-dimethylacetamide displayed the highest cytotoxicity with 5.2% at a concentration of 14.5% (v/v). According to these results, several solubilizers can alter the CBF frequency and thus, have an impact on the nasal mucosa. Therefore, CBF studies with solubilizers used at a concentration relevant for nasal formulations are essential in the design of efficient and most notably safe nasal medicinal products. PMID- 22056263 TI - Percolation-dominated superhydrophobicity and conductivity for nanocomposite coatings from the mixtures of a commercial aqueous silica sol and functionalized carbon nanotubes. AB - Superhydrophobic conductive nanocomposite coatings are prepared for the first time from the simple mixture of a commercial aqueous silica sol and functionalized multiwalled carbon nanotubes (MWNTs) by air-spraying at ambient conditions followed by fluorosilane treatment. The relationship between MWNT content and the structure and properties of the nanocomposite coatings is investigated systematically. An ultra-low threshold (<5 vol.%) for superhydrophobicity is observed, which suggests that MWNTs are superior to any other spherical fillers for the construction of superhydrophobic nanocomposite coatings. When the content of nanotubes is below the threshold, the surface roughness mainly caused by the silica nanoparticles is not enough for creating superhydrophobic surfaces. Only above the threshold, the multiscale hierarchical structure is enough for both high water contact angles (>165 degrees ) and extremely low sliding angles (<2 degrees ). The conductivity is also percolation dominated, while the threshold for conductivity is much higher than that for superhydrophobicity, which can be ascribed to the encapsulated structure and the agglomeration of nanotubes in the composite coatings during air-spraying. Moreover, the aqueous silica sols hold merits of great film-forming capability at relatively low calcination temperatures, and being free of organic solvents. PMID- 22056264 TI - Use of a three-way stopcock in grafting of autologous fat: technical note. PMID- 22056265 TI - Favourable survival of in-hospital compared to out-of-hospital refractory cardiac arrest patients treated with extracorporeal membrane oxygenation: an Italian tertiary care centre experience. AB - OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) support has been suggested to improve the survival rate in patients with refractory in- and out-of-hospital cardiac arrest (IHCA and OHCA). The aim of our study is to report our experience with ECMO in these patients. DESIGN: Retrospective, single-centre, observational study. PATIENTS: From January 2006 to February 2011 we studied 42 patients (31 males) with refractory cardiac arrest. MEASUREMENT AND MAIN RESULTS: ECMO implantation was successful in 38 (90%) of the 42 patients. ECMO support was positioned: three times (8%) in the operating room, six (16%) in the cardiac surgery intensive care unit, 21 (55%) in the emergency room, five (13%) in the catheterisation laboratory and three (8%) in the general ward. A total of 14 IHCA (58%) and three OHCA (16%) patients were weaned from ECMO (p<0.05). Eleven IHCA (46%) and one OHCA (5%, p<0.05) patients were discharged from intensive care unit (ICU). Among IHCA patients, 10 were alive at 6 months, nine of whom (38%) with good neurological outcome. Among OHCA patients weaned from ECMO, one was alive at 6 months with good neurological outcome (5%, p<0.05 vs. IHCA). CONCLUSIONS: ECMO support should be considered as a resuscitation alternative in selected patients. More specifically, patients with witnessed IHCA benefit more from ECMO treatment compared to those who experience an out-of-hospital cardiac arrest. PMID- 22056266 TI - Heart fatty acid binding protein and myoglobin do not improve early rule out of acute myocardial infarction when highly sensitive troponin assays are used. PMID- 22056267 TI - Metabolic dysfunction in the post-resuscitation heart. PMID- 22056268 TI - Basic life support - becoming more complex. PMID- 22056270 TI - The bovine CXCR1 gene is highly polymorphic. AB - Several single nucleotide polymorphisms (SNP) in the bovine CXCR1 gene have been implicated in resistance to mastitis and milk somatic cell counts in several sample populations of Holstein dairy cows. As such, a more thorough understanding of SNP present in and near the bovine CXCR1 gene is needed. This study identified 36 SNP in the coding region and surrounding sequences of CXCR1 in 88 Holstein dairy cows. Four SNP induced amino acid changes and 1 SNP an early stop codon. Two amino acid changes occur in the third intracellular loop and C-terminus in locations tied to intracellular signaling. The 36 SNP could be subdivided into 4 separate linkage groups. Using representative or 'tag' SNP from each linkage group, haplotypes or the combination of SNP found on a single allele were generated to increase the specificity of an animal's genetic background. Four haplotypes were identified that represented 99% of the sample population. The haplotypes generated using tag SNP agreed with haplotypes generated from SNP causing amino acid changes. In conclusion, the CXCR1 gene is highly polymorphic and has potential implications towards genetic selection and understanding host factors that increase the risk of infection. PMID- 22056271 TI - Flow cytometric immune profiling of specific-pathogen-free chickens before and after infectious challenges. AB - Broilers and layer chickens have been intensively selected for production parameters. This selection has affected immune capacity. Consequently, the fine tuning of immune responses is becoming important for maximum productivity. Flow cytometry is a recurrent technology used for the immunophenotyping of birds. Studies, however, have focused on the mechanism of specific diseases or have used animals whose immunological condition could be biased-by vaccination or environmental stressors, for example. The aim of this study was to evaluate the immune status of specific-pathogen-free birds across different age ranges to characterize the natural changes that occur over time. Additionally, specific pathogen-free chickens were challenged with four infectious agents, allowing identification of the subpopulations of peripheral blood immune cells that are consistently altered under various conditions. Several lymphocyte subsets vary naturally with aging, so the interpretation of results using animals of different age ranges must proceed with care. Parameters such as CD8(+)CD28(-), CD8alphaalpha(+), CD4(+)CD8(+), and CD8(+)TCRVbeta1(+) have been shown to be valuable in understanding immune changes during disease. The use of these data allows a determination of the consistency of cytometric parameters under various conditions, which should ease the interpretation of immunophenotyping and the future application of cytometric analysis in the poultry industry. PMID- 22056272 TI - A lepidopteran aminoacylase (L-ACY-1) in Heliothis virescens (Lepidoptera: Noctuidae) gut lumen hydrolyzes fatty acid-amino acid conjugates, elicitors of plant defense. AB - Fatty acid-amino acid conjugates (FACs) have been identified in Lepidopteran larvae as elicitors of plant defenses. Plant responses include the production of primary defense compounds and induction of secondary defense strategies including attraction of parasitoid wasps. These elicitors are present despite fitness costs, suggesting that they are important for the larvae's survival. In order to exploit FAC-mediated plant defense responses in agricultural settings, an understanding of FAC purpose and metabolism is crucial. To clarify their role, enzymes involved in this metabolism are being investigated. In this work a previously undiscovered FAC hydrolase was purified from Heliothis virescens frass by liquid chromatography and PAGE techniques and was identified as an aminoacylase-like protein (L-ACY-1) using MALDI-ToF/ToF and Edman sequencing. The full length gene was cloned and expressed in Escherichia coli and a polyclonal antibody against L-ACY-1 was made. L-ACY-1 was confirmed to be responsible for FAC hydrolysis activity through inhibition of N-linolenoyl-l-glutamine hydrolysis by titration with the polyclonal anti-L-ACY-1 antibody. L-ACY-1 activity is dependent on a divalent cation. This is the first time an aminoacylase has been described from an insect. L-ACY-1 appears to play a vastly different role in insects than ACYs do in mammals and may be involved in maintaining glutamine supplies for gut tissue metabolism. Identification of L-ACY-1, a FAC hydrolase, clarifies a previously uncharacterized portion of FAC metabolism. PMID- 22056273 TI - Similarity metrics for surgical process models. AB - OBJECTIVE: The objective of this work is to introduce a set of similarity metrics for comparing surgical process models (SPMs). SPMs are progression models of surgical interventions that support quantitative analyses of surgical activities, supporting systems engineering or process optimization. METHODS AND MATERIALS: Five different similarity metrics are presented and proven. These metrics deal with several dimensions of process compliance in surgery, including granularity, content, time, order, and frequency of surgical activities. The metrics were experimentally validated using 20 clinical data sets each for cataract interventions, craniotomy interventions, and supratentorial tumor resections. The clinical data sets were controllably modified in simulations, which were iterated ten times, resulting in a total of 600 simulated data sets. The simulated data sets were subsequently compared to the original data sets to empirically assess the predictive validity of the metrics. RESULTS: We show that the results of the metrics for the surgical process models correlate significantly (p<0.001) with the induced modifications and that all metrics meet predictive validity. The clinical use of the metrics was exemplarily, as demonstrated by assessment of the learning curves of observers during surgical process model acquisition. CONCLUSION: Measuring similarity between surgical processes is a complex task. However, metrics for computing the similarity between surgical process models are needed in many uses in the field of medical engineering. These metrics are essential whenever two SPMs need to be compared, such as during the evaluation of technical systems, the education of observers, or the determination of surgical strategies. These metrics are key figures that provide a solid base for medical decisions, such as during validation of sensor systems for use in operating rooms in the future. PMID- 22056274 TI - Entomopathogenic nematodes, root weevil larvae, and dynamic interactions among soil texture, plant growth, herbivory, and predation. AB - Greenhouse experiments were conducted to assess the influence of soil texture on the persistence, efficacy and plant protection ability of entomopathogenic nematodes (EPNs) applied to control larvae of the Diaprepes root weevil (DRW), Diaprepes abbreviatus, infesting potted citrus seedlings. Seedlings were grown in pots containing either coarse sand, fine sand, or sandy loam. Three DRW larvae were added to each of 80 pots of each soil type. 24 h later, 20 pots of each soil type that had received weevil larvae were inoculated with EPN infective juveniles (IJs) of one of the following species: Steinernema diaprepesi, Steinernema riobrave and Heterorhabditis indica. Pots of each soil without EPNs were established as controls with DRW and controls without DRWs. Subsequently, pots with larvae received three additional larvae monthly, and the experiment continued for 9 months. Plant root and top weights at the end of the experiment were affected by both soil (P<=0.0001) and nematodes (P<=0.0001), and nematode species protected plants differently in different soils (interaction P<=0.0001). Soil porosity was inversely related to plant damage by DRW, whether or not EPNs were present; and porosity was directly related to the level of plant protection by EPNs. Mortality of caged sentinel weevil larvae placed in pots near the end of the experiment was highest in pots treated with S. diaprepesi. In a second, similar experiment that included an additional undescribed steinernematid of the Steinernema glaseri-group, soil type affected root damage by DRW and root protection by EPNs in the same manner as in the first experiment. Final numbers of S. diaprepesi and Steinernema sp. as measured by real-time PCR were much greater than those of S. riobrave or H. indica in all soils. Across all treatments, the number of weevil larvae in soil at the end the experiment was inversely related to soil porosity. In all soils, fewer weevil larvae survived in soil treated with S. diaprepesi or Steinernema sp. than in controls with DRW or treatments with S. riobrave or H. indica. The results of these experiments support the hypothesis that EPNs provide greater protection of seedlings against DRW larvae in coarse textured soil than in finer textured soil. However, less vigorous growth of the control without DRW seedlings in the two finer textured soils suggests that unidentified factors that stressed seedlings in those soils also impaired the ability of seedlings to tolerate weevil herbivory. PMID- 22056275 TI - Novel TiO2/C nanocomposites: synthesis, characterization, and application as a photocatalyst for the degradation of organic pollutants. AB - Novel TiO(2)/carbon nanocomposites were prepared through the pyrolysis of TiO(2)/poly(furfuryl alcohol) hybrid materials, which were obtained by the sol gel method, starting from titanium tetraisopropoxide (TTIP) and furfuryl alcohol (FA) precursors. Six different TiO(2)/C samples were prepared based on different TiO(2) nanoparticle sizes and TiO(2)/FA ratios. All of the samples were characterized using X-ray diffraction, infrared, and Raman spectroscopy. The results indicated effective FA polymerization onto the TiO(2) (anatase) nanoparticles, polymer conversion to disordered carbon following the pyrolysis, and a simultaneous TiO(2) anatase-rutile phase transition. The resulting TiO(2)/carbon composites were used as photocatalysts in the advanced oxidative process (AOP) for the degradation of reactive organic dyes in aqueous solution. The results indicate excellent photocatalytic performance (degradation of 99% of the dye after 60 min) with several advantages over traditional TiO(2)-based photocatalysts. PMID- 22056276 TI - Pathophysiological alterations in oxygen delivery to the tissues. AB - This paper reviews co-factors that impact on oxygen delivery and uptake, in the attempt to unravel the mechanisms underlying the correlation between the decrease in oxygen delivery and oxygen consumption. In sequence, the following factors are analyzed that, besides a decrease in haemoglobin concentration, impair tissue metabolism: (1) lung diffusion and perfusion limitation in oxygen transport, (2) decrease in cardiac output, (3) impairment of peripheral microvascular perfusion and (4) reduced ability of cells to extract oxygen. The contribution of the various factors is modeled aiming to present a decisional flow chart for the functional evaluation of the efficiency of the oxygen transport system. PMID- 22056277 TI - Substituted thiazoles V. synthesis and antitumor activity of novel thiazolo[2,3 b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues. AB - A novel series of thiazolo[2,3-b]quinazoline (14-23, 26 and 27), and pyrido[4,3 d]thiazolo[3,2-a]pyrimidine (34-43, 45 and 46) analogues were designed and synthesized. The obtained compounds were evaluated for their in-vitro antitumor activity at the National Cancer Institute (NCI) 60 cell lines panel assay. Compounds 22, 38, 40 and 41 showed remarkable broad-spectrum antitumor activity. Compounds 22 and 38 are almost nine fold more active than 5-FU, with GI(50), TGI, and LC(50) values of 2.5, >100, >100; and 2.4, 9.1, 36.2 MUM, respectively; while 40 and 41 are almost seven fold more active than 5-FU, with GI(50), TGI, and LC(50) values of 2.9, 12.4, 46.6 and 3.0, 16.3, 54.0 MUM, respectively. PMID- 22056278 TI - Ten-year experience with fungal peritonitis in peritoneal dialysis patients: antifungal susceptibility patterns in a North-American center. AB - OBJECTIVE: To describe the clinical and microbiological features associated with fungal peritonitis in peritoneal dialysis (PD) patients at Hopital Maisonneuve Rosemont, from August 1996 to July 2006. METHODS: Cases were retrieved from the microbiology laboratory culture registry. Antifungal susceptibility was determined by the Clinical and Laboratory Standards Institute M27A3 method. RESULTS: Among 288 PD patients (total follow-up of 7258 patient-months), nine were found with fungal peritonitis. Candida spp were identified in all of them, with a majority of non-albicans Candida species. Resistance to fluconazole, itraconazole, or voriconazole was as frequent as potential resistance to amphotericin B. No isolate was resistant to caspofungin and one was resistant to micafungin. Prior bacterial peritonitis was frequent (67%). All patients had their PD catheter removed and all of them survived. CONCLUSIONS: In our institution, fungal peritonitis in PD patients is rare. All cases were caused by Candida species. Variable susceptibility patterns were observed, which may influence the initial empirical antifungal therapy and underscore the importance of individual speciation and susceptibility testing of invasive Candida isolates. PMID- 22056279 TI - The maturity of modeling. A comment on "Modeling the Cultural Evolution of Language" by Luc Steels. PMID- 22056280 TI - 'Emotion'. 'The essence of Human communication - the processing of emotional information'. Comment on: Bruck C, Kreifelts B, Wildgruber D. Emotional voices in context: a neurobiological model of multimodal affective information processing. PMID- 22056281 TI - Association of epilepsy and type 1 diabetes mellitus in children and adolescents: is there an increased risk for diabetic ketoacidosis? AB - OBJECTIVE: To estimate the prevalence of epilepsy and possible risk factors in children and adolescents with diabetes mellitus. STUDY DESIGN: We conducted an observational cohort study based on the Diabetes Patienten Verlaufsdokumentation database including data from 45 851 patients (52% male) with type 1 diabetes mellitus, age 13.9 +/- 4.3 years (mean +/- SD) and duration of diabetes mellitus 5.4 +/- 4.2 years. The database was searched for the concomitant diagnosis of epilepsy or epileptic convulsions and for antiepileptic medication. RESULTS: A total of 705 patients with epilepsy were identified, giving a prevalence of 15.5 of 1000. A total of 375 patients were treated with antiepileptic medication, and 330 patients were without anticonvulsive therapy. Patients with epilepsy were younger at onset of diabetes mellitus and shorter than patients without epilepsy, and their weight and body mass index were comparable. No difference could be demonstrated for metabolic control, type of insulin treatment, insulin dose, and prevalence of B-cell specific autoantibodies. The frequency of severe hypoglycemia was lower in patients treated with antiepileptic medication. The risk for diabetic ketoacidosis was almost double in patients with epilepsy compared with patients with type 1 diabetes mellitus alone (P < .01). CONCLUSION: Children and adolescents with diabetes mellitus show an increased prevalence of epileptic seizures. For unknown reasons, there is an association between epilepsy and diabetic ketoacidosis in children with type 1 diabetes mellitus. PMID- 22056283 TI - Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants. AB - OBJECTIVE: To examine associations between brain white matter abnormalities, including diffuse excessive high signal intensities, detected on neonatal magnetic resonance imaging (MRI) with neurodevelopmental outcome at age 30 months. STUDY DESIGN: This was a prospective, population-based study of infants born at <27 weeks gestation (n=117) undergoing conventional MRI at term equivalent age (n=107). At age 30 months corrected, 91 of the preterm infants (78%) and 85 term-born controls were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS: Cerebral palsy (CP) was present in 7% of the preterm group. On the BSID-III, mean composite scores were 96+/-9.5 for the cognitive scale, 97+/-14 for language scales, and 103+/-15 for motor scales, all within the normal range for age. Compared with the term born controls, however, the preterm infants did not perform as well on all 3 scales, also when MRI was normal. Significant associations were seen between moderate to severe white matter abnormalities and CP (P<.001). The presence of diffuse excessive high signal intensities was not associated with performance on the BSID-III or with CP. CONCLUSION: This 3-year cohort of extremely preterm infants had low rates of major brain injury and impaired outcome. Neonatal MRI provides useful information, but this information needs to be treated with caution when predicting outcome. PMID- 22056282 TI - Association of cord blood magnesium concentration and neonatal resuscitation. AB - OBJECTIVE: To assess the relationship between umbilical cord blood magnesium concentration and level of delivery room resuscitation received by neonates. STUDY DESIGN: This was a secondary analysis of a controlled fetal neuroprotection trial that enrolled women at imminent risk for delivery between 24 and 31 weeks' gestation and randomly allocated them to receive either intravenous magnesium sulfate or placebo. The cohort included 1507 infants with data available on total cord blood Mg concentration and delivery room resuscitation. Multivariate logistic regression was used to estimate the association between cord blood Mg concentration and highest level of delivery room resuscitation, using the following hierarchy: none, oxygen only, bag-mask ventilation with oxygen, intubation, and chest compressions. RESULTS: There was no relationship between cord blood Mg and delivery room resuscitation (OR, 0.92 for each 1.0-mEq/L increase in Mg; 95% CI, 0.83-1.03). Maternal general anesthesia was associated with increased neonatal resuscitation (OR, 2.51; 95% CI, 1.72-3.68). Each 1-week increase in gestational age at birth was associated with decreased neonatal resuscitation (OR, 0.63; 95% CI, 0.60-0.66). CONCLUSION: Cord blood Mg concentration does not correlate with the level of delivery room resuscitation of infants exposed to magnesium sulfate for fetal neuroprotection. PMID- 22056284 TI - Major contribution of Adelta-fibres to increased reflex transmission in the feline spinal cord during acute muscle inflammation. AB - The contribution of activated nociceptive muscle afferents to pathologically increased muscle tone remains obscure. The aim of the present study was to investigate whether an acute myositis of the gastrocnemius-soleus (GS) influences spinal reflex activity and to test whether Adelta-fibre or C-fibre were mainly responsible for any effects. In high spinal cats monosynaptic reflexes (MRs) of flexors and extensors and transmission in reflex pathways from group III and IV muscle afferents (activated by intra-arterial KCl injection) were investigated. After infiltration of GS with carrageenan there was a distinct increase in the MRs of flexors and extensors, coupled with facilitation of the flexors, induced by chemically activated group III and IV afferents. The inhibition evoked in extensors by these afferents was also mainly enhanced but less consistently. The reflex effects of carrageenan started within 1h and reached their maximum after about 1.5h. After blocking the input of all myelinated A-fibres, including Adelta fibres, from the inflamed muscle by TTX, only a small facilitatory effect on MRs remained and the facilitation of excitatory transmission in the excitatory pathway to the flexor PBSt was abolished. The results show that the action of carrageenan-induced inflammation on spinal reflex function derives mainly from Adelta-fibres. PMID- 22056285 TI - Gradient nanofibrous chitosan/poly E-caprolactone scaffolds as extracellular microenvironments for vascular tissue engineering. AB - One of the major challenges of tissue-engineered small-diameter blood vessels is restenosis caused by thrombopoiesis. The goal of this study was to develop a 3D gradient heparinized nanofibrous scaffold, aiding endothelial cells lined on the lumen of blood vessel to prevent thrombosis. The vertical graded chitosan/poly E caprolactone (CS/PCL) nanofibrous vessel scaffolds were fabricated with chitosan and PCL by sequential quantity grading co-electrospinning. To mimic the natural blood vessel microenvironment, we used heparinization and immobilization of vascular endothelial growth factor (VEGF) in the gradient CS/PCL. The quantity of heparinized chitosan nanofibers increased gradually from the tunica adventitia to the lumen surfaces in the gradient CS/PCL wall of tissue engineered vessel. More heparin reacted to chitosan nanofiber in gradient CS/PCL than in uniform CS/PCL nanofibrous scaffolds. Antithrombogenic properties of the scaffolds were enhanced by the heparinization of these scaffolds, as shown by activated partial thromboplastin time and platelet adhesion assay. Compared to the uniform CS/PCL scaffold, the release of VEGF from the gradient CS/PCL was more stable and sustained, and the burst release of VEGF was reduced approximately 42.5% within the initial 12 h. The adhesion and proliferation of human umbilical vein endothelial cells (HUVEC) were enhanced on the gradient CS/PCL scaffold. Furthermore, HUVEC grew and formed an entire monolayer on the top side of the gradient CS/PCL scaffold. Therefore, use of vertical gradient heparinized CS/PCL nanofibrous scaffolds could provide an approach to create small-diameter blood vessel grafts with innate properties of mammalian vessels of anticoagulation and rapid induction of re-endothelialization. PMID- 22056286 TI - Allogeneic human tissue-engineered blood vessel. AB - BACKGROUND: Arterial bypass graft implantation remains the primary therapy for patients with advanced cardiovascular disease; however, there is no available synthetic small-diameter vascular graft. METHODS: Tissue-engineered vessels were grown from human smooth muscle cells that were seeded on a biodegradable scaffold using a biomimetic perfusion system. The human tissue-engineered vessels (hTEV) were decellularized by a two-step process using a combination of detergents and hypertonic solutions. The mechanical characteristics were assessed by suture retention strength and burst pressure. The decellularized hTEV were implanted as aortic interpositional grafts in nude rats to evaluate in vivo performance as an arterial graft over a 6-week period. RESULTS: The human tissue-engineered structure formed a vessel composed of smooth muscle cells and the extracellular matrix proteins, including collagen. After decellularization, the collagen matrix remained intact while the cellular components were removed. The mechanical strength of the hTEV after decellularization was similar to human vein in vitro, with a burst pressure of 1,567 +/- 384 mm Hg (n = 3) versus 1,680 +/- 307 mm Hg for human saphenous vein. The hTEVs had a high patency rate (four of five grafts) without evidence of rupture or aneurysm over a 6-week period as an aortic interpositional graft in a nude rat model. Histologic analysis showed a thin neointima with a confluent endothelium and a subendothelial layer of smooth muscle cells on the explanted tissue-engineered vessels. Transmission electron microscopy on the explanted tissue demonstrated elastin formation in the neointima and intact residual collagen fibers from the tissue-engineered vessel. CONCLUSIONS: The hTEV had a high patency rate and remained mechanically stable as an aortic interpositional graft in a nude rat. The vessel supported the growth of a neointima with endothelial cells and smooth muscle cells. The host remodeling suggested the engineered matrix had a positive effect to create a regenerated vascular graft. PMID- 22056287 TI - Remote and local ischemic preconditioning equivalently protects rat skeletal muscle mitochondrial function during experimental aortic cross-clamping. AB - OBJECTIVE: This study investigated whether remote (rIPC) and local ischemic preconditioning (IPC) similarly limit skeletal muscle dysfunction induced by aortic cross-clamping. METHODS: Rats were divided in three groups: the sham operated control group (C) underwent surgery without clamping. The ischemia reperfusion group (IR) had 3 hours of ischemia induced by aortic clamping and collateral vessels ligation, followed by 2 hours of reperfusion. The IPC group had, before prolonged ischemia, three bouts of 10 minutes of ischemia and 10 minutes of reperfusion on the right hind limb. Thus, right hind limbs had local IPC and left hind limbs had rIPC. Complexes I, II, III, and IV activities of the mitochondrial respiratory chain of the gastrocnemius muscle were measured using glutamate-malate (V(max)), succinate (V(succ)), and N,N,N',N'-tetramethyl-p phenylenediamine dihydrochloride (TMPD)-ascorbate (V(TMPD)). Expressions of genes involved in apoptosis (Bax, Bcl-2) and antioxidant defense (superoxide dismutase 1 [SOD 1], SOD2, glutathione peroxidase [GPx]) were determined by quantitative real-time polymerase chain reaction. Glutathione was also measured. RESULTS: Right and left hind limb mitochondrial functions were similar in controls and after IR. IR reduced V(max) (-21.2%, 6.6 +/- 1 vs 5.2 +/- 1 MUmol O(2)/min/g dry weight, P = .001), V(succ) (-22.2%, P = .032), and V(TMPD) (-22.4%, P = .033), and increased Bax (63.4%, P = .020) and Bax/Bcl-2 ratio (+84.6%, P = .029). SODs and GPx messenger RNA were not modified, but glutathione tended to be decreased after IR. Local IPC and rIPC counteracted similarly these deleterious effects, restoring mitochondrial maximal oxidative capacities and normalizing Bax, the Bax/Bcl-2 ratio, and glutathione. CONCLUSIONS: Remote ischemic preconditioning protection against IR injury is equivalent to that achieved by local IPC. It might deserve a broader use in clinical practice. CLINICAL RELEVANCE: Acute and chronic ischemia induce mitochondrial dysfunction in human skeletal muscles, and improving muscle mitochondrial function improves subjects' status. Compared with local ischemic preconditioning (IPC), remote IPC (rIPC) appears easier to perform and is safer for the vessel and territory involved in ischemic injury. This study demonstrates that the muscle protection afforded by rIPC is equivalent to that achieved by IPC. Acknowledging that IPC procedures should be specifically adapted to patient characteristics to be successful, our results support a broader use of rIPC in the setting of vascular surgery. PMID- 22056288 TI - Cicatricial iatrogenic lower eyelid malposition in skin cancer surgery: results of a combined approach. AB - PURPOSE: Malposition of the lower lid, including rounding of the lateral canthal angle, lower eyelid retraction with inferior scleral show, and ectropion, is a relatively frequent complication in the surgical treatment of skin cancer of the cheek and zygomatic areas. The tarsal strip technique, in association with a vertical vector cheek lift, is a reliable method for correcting lower lid malposition. MATERIALS AND PATIENTS: From January 2008 to January 2010, we treated 19 patients with lower eyelid malposition after skin cancer surgery of the cheek and zygomatic areas. To correct lower eyelid malposition, we used the tarsal strip technique and a vertical vector cheek lift in all patients. RESULTS: Eleven patients had scleral show and eight patients had ectropion. Sixteen patients obtained satisfactory correction of the eyelid malposition in a single surgical procedure, while three patients required a second surgical step to correct the remaining scleral show. Good esthetic and functional results were achieved in all cases. CONCLUSIONS: The surgical treatment of skin cancer of the cheek and zygomatic areas has the potential for postoperative sequelae. The tarsal strip technique, in association with a vertical vector cheek lift, is a relatively simple technique for correcting scleral show and ectropion. PMID- 22056289 TI - Reassembling (social) contexts: New directions for a sociology of drugs. PMID- 22056290 TI - Drug effects, performativity and the law. PMID- 22056291 TI - Relapse and therapeutic interventions in a 1-year observational cohort study of nonadherent outpatients with schizophrenia. AB - OBJECTIVES: To evaluate the incidence rate of relapse, the clinical profiles, and the therapeutic interventions employed for patients with schizophrenia deemed as likely nonadherers to oral antipsychotic drugs. METHODS: A cohort of 597 outpatients whose therapy was modified because of a psychiatrist-perceived risk of nonadherence was followed for 12 months in an observational study. Baseline correlates of subsequent relapse were analyzed with Cox regression. RESULTS: At baseline, patients' mean (SD) age and time since diagnosis were 40.1 (11.1) and 15.2 (10.0) years, respectively; 63.7% were males. The Clinical Global Impression scale-Severity (CGI-S) score was >= 4 in 87.3% of the patients. Antipsychotic drugs were modified in 506 patients (84.8%); nonpharmacologic therapies were modified in 190 patients (31.8%). In both cases, the primary reason for the modifications was insufficient efficacy of current therapeutic regimen. The proportion of patients in oral antipsychotic monopharmacy decreased from 83.8% to 57.6%; 15.4% started long-acting (depot) formulations. Over the 12-month observation period, 90 patients (15.1%) relapsed. The hazard rate of relapse was higher in patients with substance use disorder or familial psychiatric antecedents and lower in patients who underwent modifications of nonpharmacological therapies or with negative attitude toward antipsychotic medication at baseline. CONCLUSIONS: Effective interventions to prevent relapse in patients with long-standing schizophrenia involving therapeutic challenges related to nonadherence are feasible. Rationale for the baseline correlates, and cues for clinical prevention of relapse in these patients are provided. PMID- 22056292 TI - Prevalence of metabolic syndrome in bipolar disorder: an exploratory study from North India. AB - PURPOSE: To study the prevalence of metabolic syndrome in patients with bipolar disorder. MATERIAL AND METHOD: By using purposive random sampling 200 patients with bipolar disorder receiving treatment were evaluated for presence of metabolic syndrome using International Diabetes Federation (IDF) and modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) criteria. RESULTS: Eighty patients fulfilled IDF criteria and 82 patients met NCEP ATP-III criteria for metabolic syndrome. There was significant concordance between these two criteria sets for metabolic syndrome (Kappa value 0.979, p<0.015). Among the individual parameters studied--increased waist circumference (70.1%) was the most common abnormality, followed by increased blood pressure (44.5%) and increased triglycerides levels (42%). Compared to patients without metabolic syndrome, patients with metabolic syndrome had significantly higher body mass index and higher percentage of them (74.4% vs 51.7%) were more than 35 years of age. Logistic regression analysis revealed that these two variables significantly predicted metabolic syndrome. CONCLUSION: Findings of the present study suggest that abdominal obesity is the most common abnormality and metabolic syndrome is best predicted in patients with bipolar disorder by higher age and higher body mass index. PMID- 22056293 TI - Substrate kringle-mediated catalysis by the streptokinase-plasmin activator complex: critical contribution of kringle-4 revealed by the mutagenesis approaches. AB - Streptokinase (SK) is a protein co-factor with a potent capability for human plasminogen (HPG) activation. Our previous studies [1] have indicated a major role of long-range protein-protein contacts between the three domains (alpha, beta, and gamma) of SK and the multi-domain HPG substrate (K1-K5CD). To further explore this phenomenon, we prepared truncated derivatives of HPG with progressive removal of kringle domains, like K5CD, K4K5CD, K3-K5CD (K3K4K5CD), K2 K5CD (K2K3K4K5CD) and K1-K5CD (K1K2K3K4K5CD). While urokinase (uPA) cleaved the scissile peptide in the isolated catalytic domain (MUPG) with nearly the same rate as with full-length HPG, SK-plasmin showed only 1-2% activity, revealing mutually distinct mechanisms of HPG catalysis between the eukaryotic and prokaryotic activators. Remarkably, with SK.HPN (plasmin), the 'addition' of both kringles 4 and 5 onto the catalytic domain showed catalytic rates comparable to full length HPG, thus identifying the dependency of the "long-range" enzyme substrate interactions onto these two CD-proximal domains. Further, chimeric variants of K5CD were generated by swapping the kringle domains of HPG with those of uPA and TPA (tissue plasminogen activator), separately. Surprisingly, although native-like catalytic turnover rates were retained when either K1, K2 or K4 of HPG was substituted at the K5 position in K5CD, these were invariably lost once substituted with the evolutionarily more distant TPA- and uPA-derived kringles. The present results unveil a novel mechanism of SK.HPN action in which augmented catalysis occurs through enzyme-substrate interactions centered on regions in substrate HPG (kringles 4 and 5) that are spatially distant from the scissile peptide bond. PMID- 22056295 TI - Experimental and histological investigations of the bone using two different oscillating osteotomy techniques compared with conventional rotary osteotomy. AB - Over the past decade, coinciding with the appearance of a number of new ultrasonic surgical devices, there has been a marked increase in interest in the use of ultrasound in oral surgery and implantology as alternative osteotomy method. The aim of this study was the comparison of the effect of osteotomies performed using ultrasonic surgery (Piezosurgery((r))), sonic surgery SONICflex((r)) and the conventional bur method on the heat generation within the bone underneath the osteotomy and light-microscopy observations of the bone at different cutting positions in porcine mandibular segments. It was found that the average heat generated by SONICflex((r)) sonic device was close to that by conventional rotary bur (1.54-2.29 degrees C), whereas Piezosurgery((r)) showed a high generated heat up to 18.17 degrees C. Histological investigations of the bone matrix adjacent to the defect radius showed intact osteocytes with all three instruments and similar wide damage diameter at the bottom region. SONICflex((r)) showed smooth cutting surfaces with minimal damage in the upper defect zone. Finally, presented results showed that sonic surgery performed with SONICflex((r)) is an alternative osteotomy method and can be used as an alternative to the conventional bur method. PMID- 22056294 TI - Wheel running attenuates microglia proliferation and increases expression of a proneurogenic phenotype in the hippocampus of aged mice. AB - Aging is associated with low-grade neuroinflammation including primed microglia that may contribute to deficits in neural plasticity and cognitive function. The current study evaluated whether exercise modulates division and/or activation state of microglia in the dentate gyrus of the hippocampus, as activated microglia can express a classic inflammatory or an alternative neuroprotective phenotype. We also assessed hippocampal neurogenesis to determine whether changes in microglia were associated with new neuron survival. Adult (3.5 months) and aged (18 months) male BALB/c mice were individually housed with or without running wheels for 8 weeks. Mice received bromodeoxyuridine injections during the first or last 10 days of the experiment to label dividing cells. Immunofluorescence was conducted to measure microglia division, co-expression of the neuroprotective indicator insulin-like growth factor (IGF-1), and new neuron survival. The proportion of new microglia was increased in aged mice, and decreased from wheel running. Running increased the proportion of microglia expressing IGF-1 suggesting exercise shifts microglia phenotype towards neuroprotection. Additionally, running enhanced survival of new neurons in both age groups. Findings suggest that wheel running may attenuate microglia division and promote a proneurogenic phenotype in aged mice. PMID- 22056296 TI - Meniscal allograft transplantation without bone plugs: a 3-year minimum follow-up study. AB - BACKGROUND: Meniscal allograft transplantation is a viable option for subtotally meniscectomized and totally meniscectomized symptomatic patients and potentially results in pain relief and increased function. HYPOTHESIS: The use of a single tibial tunnel arthroscopic technique without bone plugs will reduce symptoms (pain) and improve knee function at a minimum 3-year follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-two meniscal transplantations (16 medial, 16 lateral; 23 men, 9 women) were prospectively evaluated at a minimum of 36 months (mean, 40.4 +/- 6.90 months; range, 36-66 months) after surgery. The average age at the time of surgery was 35.6 +/- 10.3 years (range, 15-55 years). The transplantation was performed using an arthroscopic bone plug free technique with a single tibial tunnel plus "all-inside" meniscal sutures. The anterior meniscal horn was sutured to the capsule. Follow-up included a visual analog scale (VAS) score for knee pain and subjective and objective International Knee Documentation Committee (IKDC), Lysholm, Tegner, and SF-36 scores. All patients underwent radiographic and magnetic resonance imaging (MRI) evaluation of the involved knee before the surgery and at the final follow-up. The MRI outcomes were evaluated with the modified Yulish score. RESULTS: Regarding clinical evaluation, there was a significant improvement in scores at follow-up compared with preoperatively: the VAS score decreased from 70.6 +/- 21.7 to 25.2 +/- 22.7 (P < .0001), the SF-36 physical component score increased from 37.31 +/- 7.2 to 49.69 +/- 8.3 (P < .0001), the SF-36 mental component score increased from 49.69 +/- 10.8 to 53.53 +/- 7.5 (P = .0032), the Tegner activity score increased from 3 (range, 3-5) to 5 (range, 3-6) (P < .0121), the Lysholm score increased from 59.78 +/- 18.25 to 84.84 +/- 14.4 (P < .0001), the subjective IKDC score increased from 47.44 +/- 20.60 to 77.20 +/- 15.57 (P < .0001), and the objective IKDC score changed from 1 A, 21 B, 6 C, and 4 D to 22 A, 9 B, and 1 C (P < .0001). No significant difference was found in this study between patients who received medial allografts and patients who received lateral allografts. There was no significant difference between outcomes of patients with isolated and combined procedures. The MRI findings showed 69% extruded allografts (8 medial and 14 lateral). In detail, we found 50% of the medial allografts and 87% of the lateral allografts extruded. No significant difference in clinical outcomes and modified Yulish score was found between patients with extruded allografts and with in situ allografts. The MRI results also showed a significant decrease of the modified Yulish score from baseline to 3-year minimum follow-up (P < .0001 for femur and P < .0001 for tibia). Only one patient underwent arthroscopic selective meniscectomy because of a medial posterior horn retear of the graft. One patient developed lack of flexion and underwent an arthroscopic arthrolysis. These 2 patients did not draw benefit from allografting and therefore were considered failures. In all remaining cases (94%), meniscal allograft transplantation was able to reduce symptoms (pain measured by VAS) and improve knee function (as measured by IKDC and Lysholm scores). CONCLUSION: This study found that a single tibial tunnel arthroscopic technique without bone plugs for meniscal allograft transplantation significantly reduced pain and improved knee function in 94% of patients at a minimum 3-year follow-up. PMID- 22056297 TI - Female-biased infection and transmission of the gastrointestinal nematode Trichuris arvicolae infecting the common vole, Microtus arvalis. AB - Previous studies addressing the importance of host gender in parasite transmission have shed light on males as the more important hosts, with the higher transmission potential of males being explained by the fact that they often harbour higher parasite loads than females. However, in some systems females are more heavily infected than males and may be responsible for driving infection under such circumstances. Using a wild population of common voles (Microtus arvalis), we showed that females were more frequently infected by the intestinal nematode Trichuris arvicolae than males (i.e. prevalence based on the presence of eggs in the faeces) and that females were shedding greater numbers of parasite eggs per gram of faeces (EPG) than males. By applying an anthelmintic treatment to either male or female voles, we demonstrated that treating females significantly reduced parasite burdens (i.e. prevalence and EPG) of both male and female hosts, while treating males only reduced parasite burden in males. These findings indicate that in this female-biased infection system females play a more important role than males in driving the dynamics of parasite transmission. PMID- 22056298 TI - Unenhanced computed tomography to identify intrahepatic and extrahepatic limy bile. PMID- 22056299 TI - Travel-associated health risks for patients with inflammatory bowel disease. AB - BACKGROUND & AIMS: There are few data on risk of travel for patients with inflammatory bowel disease (IBD). We assessed rates of illness while traveling among patients with IBD. METHODS: We performed a retrospective, case-controlled study of illnesses among 222 patients with IBD and 224 healthy individuals (controls) during 1099 total trips. Data were retrieved by structured questionnaires, personal interviews, and chart review. RESULTS: Participants had 142 episodes of illness during the trips; 92% were enteric disease. An episode of illness occurred during 79/523 (15.1%) trips made by patients with IBD compared with 63/576 (10.9%) trips made by controls (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.01-2.0; P = .04). However, this difference was mostly attributable to the increased incidence of illness among IBD patients traveling in industrialized countries. In contrast, the rate of illness among travelers to developing countries was similar among patients with IBD and controls (34/200, 17% vs 52/243, 21% of trips, respectively; P = .24). Moreover, numerically more controls that traveled to the tropics developed illness than travelers with IBD (43/135 vs 23/97, respectively; P = .18). In multivariate analysis, factors that increased risk for travel illness included frequent flares of IBD (OR, 1.9; 95% CI, 1.1-3.4; P = .02) and prior IBD-related hospitalizations (OR, 3.5; 95% CI, 1.3-9.3; P = .01); remission within 3 months before traveling reduced the risk for illness (OR, 0.3; 95% CI, 0.16-0.5; P < .001). Use of immunomodulatory drugs was not independently associated with risk of illness during travel. CONCLUSIONS: Patients with IBD have a higher rate of illness compared with controls during trips to industrialized countries, but not to developing or tropical regions. These findings indicate that most travel-associated illnesses stem from sporadic IBD flares rather than increased susceptibility to enteric infections. PMID- 22056300 TI - Autoimmune hepatitis after liver transplantation. AB - Liver transplantation is an effective treatment for patients with end-stage acute and chronic autoimmune hepatitis. However, despite the good outcomes reported, disease recurrence is relatively common in the allograft. In addition, autoimmunity and autoimmune liver disease can arise de novo after transplantation for non-autoimmune liver disorders. Little is known about the mechanisms by which autoimmune diseases develop after liver transplantation, but genetic factors, molecular mimicry, impaired regulatory T-cell responses, and exposures to new alloantigens might be involved. Regardless of the pathogenic mechanisms, it is important to remain aware of the existence of recurrent and de novo autoimmune hepatitis after liver transplantation; these disorders are similar to classic autoimmune hepatitis and are therefore not treated with standard antirejection strategies. PMID- 22056301 TI - Latest generation, wide-angle, high-definition colonoscopes increase adenoma detection rate. AB - BACKGROUND & AIMS: Improvements to endoscopy imaging technologies might improve detection rates of colorectal cancer and patient outcomes. We compared the accuracy of the latest generation of endoscopes with older generation models in detection of colorectal adenomas. METHODS: We compared data from 2 prospective screening colonoscopy studies (the Berlin Colonoscopy Project 6); each study lasted approximately 6 months and included the same 6 colonoscopists, who worked in private practice. Participants in group 1 (n = 1256) were all examined by using the latest generation of wide-angle, high-definition colonoscopes that were manufactured by the same company. Individuals in group 2 (n = 1400) were examined by endoscopists who used routine equipment (a mixture of endoscopes from different companies; none of those used to examine group 1). The adenoma detection rate was calculated on the basis of the number of all adenomas/number of all patients. RESULTS: There were no differences in patient parameters or withdrawal time between groups (8.0 vs 8.2 minutes). The adenoma detection rate was significantly higher in group 1 (0.33) than in group 2 (0.27; P = .01); a greater number of patients with least 1 adenoma were identified in group 1 (22.1%) than in group 2 (18.2%; P = .01). A higher percentage of high-grade dysplastic adenomas were detected in group 1 (1.19%) than in group 2 (0.57%), but this difference was not statistically significant (P = .06). CONCLUSIONS: The latest generation of wide-angle, high-definition colonoscopes improves rates of adenoma detection by 22%, compared with mixed, older technology endoscopes used in routine private practice. These findings might affect definitions of quality control parameters for colonoscopy screening for colorectal cancer. PMID- 22056302 TI - Colonoscopy with clipping is useful in the diagnosis and treatment of diverticular bleeding. AB - BACKGROUND & AIMS: Diverticular bleeding is the most common cause of acute severe lower gastrointestinal bleeding (LGIB) in Western countries. Diagnostic and therapeutic approaches, including endoscopy, radiology, or surgery, have not been standardized. We investigated colonoscopy as a first-line modality to diagnose and manage patients with LGIB. METHODS: We performed a retrospective study of data collected from 2 tertiary Veterans hospitals of 64 patients (61 men, 76 +/- 11 years) with acute severe diverticular bleeding, based on colonoscopy examination. We assessed primary hemostasis using endoscopic clipping for diverticular bleeding and described the bleeding stigmata. We measured early (<30 days) and late rebleeding, blood transfusion requirements, hospital stay and complications. RESULTS: Patients received 3.1 +/- 3.0 and 0.9 +/- 2.2 U of blood before and after colonoscopy, respectively. Twenty-four of the 64 patients (38%) had diverticular stigmata of recent hemorrhage; and 21 of these patients (88%) were treated successfully using endoscopic clips, without complication or early rebleeding. Hospital stays averaged 6.4 +/- 5.6 days. Endoscopic clipping provided primary hemostasis in 9/12 patients (75%) with active diverticular bleeding. During 35 +/- 18 months of follow-up, late recurrent diverticular bleeding occurred in 22% of the patients (14/64) after a mean time period of 22 months; 5 of the patients (21%) with stigmata of recent hemorrhage who received clip treatment had rebleeding at 43 months. Rebleeding was self-limited in 8 patients (57%), was clipped in 4 (29%), or was embolized in 2 (14%). CONCLUSIONS: Colonoscopy can be a safe first-line diagnostic and therapeutic approach for patients with severe LGIB. Endoscopic clipping provides hemostasis of active diverticular bleeding. Recurrent bleeding occurs in about 21% of patients who were treated with clips, at approximately 4 years; most bleeding is self-limited or can be retreated by endoscopic clipping. PMID- 22056303 TI - Safety of prior endoscopic mucosal resection in patients receiving radiofrequency ablation of Barrett's esophagus. AB - BACKGROUND & AIMS: Radiofrequency ablation (RFA) is safe and effective treatment for flat dysplasia associated with Barrett's esophagus (BE). However, there are limited data on the safety of RFA in patients who had prior endoscopic mucosal resection (EMR), which might increase the risk of complications. We compared complications and histologic outcomes between patients who had EMR before RFA and those who received only RFA. METHODS: We performed a retrospective analysis of data collected from patients treated for BE, associated with dysplasia or intramucosal cancer, at the Mayo Clinic in Rochester, Minnesota, from 1998-2009. Patients were divided into groups that had RFA after EMR (group 1, n = 44) or only RFA (group 2, n = 46). We compared the incidence of complications (strictures, bleeding, and esophageal perforation) and histologic features (complete resolution of dysplasia and complete resolution of intestinal metaplasia [CR-IM]) between groups. Logistic regression analysis was performed to assess predictors of stricture formation. RESULTS: Stricture rates were 14% in group 1 and 9% in group 2 (odds ratio, 1.53; 95% confidence interval [CI], 0.26 9.74). The rates of CR-IM were 43% in group 1 and 74% in group 2 (odds ratio, 0.33; 95% CI, 0.14-0.78). The rates of complete resolution of dysplasia were 76% in group 1 and 71% in group 2 (odds ratio, 1.28; 95% CI, 0.39-4.17). The adjusted odds ratio for CR-IM in group 1 (adjusting for age, segment length, and grade of dysplasia) was 0.50 (95% CI, 0.15-1.66). CONCLUSIONS: Stricture rates among patients who receive only RFA are comparable to those of patients who had prior EMR. EMR appears safe to perform prior to RFA. PMID- 22056304 TI - Hemosuccus pancreaticus diagnosed with concurrent endoscopic retrograde pancreatography and selective angiography. PMID- 22056305 TI - TAp63gamma enhances nucleotide excision repair through transcriptional regulation of DNA repair genes. AB - p63 and p73, two p53 family members, play crucial roles in development and tumor suppression. p63 and p73 have multiple isoforms, which have similar or distinct biological functions. Transactivation (TA) isoforms of p63 and p73 have high similarity with p53 and often have biological functions similar to p53. p53 plays an important role in nucleotide excision repair (NER) through transcriptional regulation of target genes involved in NER, including DDB2, XPC and GADD45. To investigate whether TAp63 and TAp73 play a similar role in NER, Saos2 cells with inducible expression of specific isoforms of TAp63 and TAp73, including TAp63alpha/beta/gamma and TAp73alpha/beta/gamma isoforms, were employed. Overexpression of TAp63gamma significantly enhances NER of ultraviolet (UV) induced DNA damage, including cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts, and enhances cell survival after UV irradiation in Soas2 cells. The enhancement of NER of UV-induced DNA damage by TAp63gamma was also confirmed in H1299 cells with overexpression of TAp63gamma. Consistently, knockdown of endogenous TAp63 decreases NER of UV-induced DNA damage in H1299 cells. TAp63alpha/beta and TAp73alpha/beta/gamma isoforms do not have a clear effect on NER in Saos2 or H1299 cells. TAp63gamma overexpression clearly induces the expression of DDB2, XPC and GADD45 at both RNA and protein levels. Furthermore, luciferase reporter assays show that TAp63gamma transcriptionally activates DDB2, XPC and GADD45 genes through the regulation of the p53 binding elements in these genes. These results demonstrate that TAp63gamma enhances NER to remove UV induced DNA damage and maintain genomic stability through transcriptional induction of a set of NER proteins, which provides an additional important mechanism that contributes to the function of TAp63 in tumor suppression. PMID- 22056306 TI - DNA polymerase eta is targeted by Mdm2 for polyubiquitination and proteasomal degradation in response to ultraviolet irradiation. AB - DNA polymerase eta (PolH), the product of the xeroderma pigmentosum variant (XPV) gene and a Y-family DNA polymerase, plays a pivotal role in translesion DNA synthesis. Loss of PolH leads to early onset of malignant skin cancer in XPV patients and increases UV-induced carcinogenesis. Thus, the pathways by which PolH expression and activity are controlled may be explored as a strategy to prevent UV-induced cancer. In this study, we found that Mdm2, a RING finger E3 ligase, promotes PolH degradation. Specifically, we showed that knockdown of Mdm2 increases PolH expression in both p53-proficient and -deficient cells. In addition, we showed that UV-induced PolH degradation is attenuated by Mdm2 knockdown. In contrast, ectopically expression of Mdm2 decreases PolH expression, which can be abrogated by the proteasome inhibitor MG132. Moreover, we showed that Mdm2 physically associates with PolH and promotes PolH polyubiquitination in vivo and in vitro. Finally, we showed that knockdown of Mdm2 increases the formation of PolH replication foci and decreases the sensitivity of cells to UV induced lesions in a PolH-dependent manner. Taken together, we uncovered that Mdm2 serves as an E3 ligase for PolH polyubiquitination and proteasomal degradation in cells under the basal condition and in response to UV irradiation. PMID- 22056307 TI - Erectile dysfunction and diabetes: a review of the current evidence-based medicine and a synthesis of the main available therapies. AB - AIM: This review aimed to provide an update of the epidemiology, pathophysiology and management of erectile dysfunction (ED) in diabetes patients. METHODS: Data on the management of ED in diabetes patients in the literature were analyzed using Medline, and by matching the following keywords: diabetes; erectile dysfunction; endothelial dysfunction; cardiovascular disease; phosphodiesterase inhibitors; intracavernous injection; and penile prosthesis. RESULTS: ED has a higher incidence in diabetic patients. The pathophysiology is multifactorial, involving endothelial dysfunction, specific complications of diabetes and psychological factors. Recent studies have shown that ED is able to predict future cardiovascular events not only in non-diabetics, but also in patients with diabetes. ED could also be a potential marker to screen for silent coronary artery disease. The management of ED has been revolutionized by the discovery of phosphodiesterase type-5 (PDE5) inhibitors, the first-line therapeutic options for diabetic men with ED that are efficient and safe. As a second line, intracavernous injections remain a gold-standard treatment, although a vacuum device can be used as well. In cases of failure, penile prosthesis may be considered. Hypogonadism, commonly found in diabetics, may require identification and treatment. Optimalized glycaemic control, management of associated co morbidities and lifestyle modifications are essential in all patients. As ED and diabetes negatively impact male self-esteem, and generate depression and anxiety, the psychological treatment of patients is also likely to be beneficial. CONCLUSION: The aetiology of diabetic ED is multifactorial. Endothelial dysfunction is the link between diabetes-induced ED and coronary artery disease. A global approach is needed for the successful management of diabetic ED. PMID- 22056308 TI - Commentary to 'Ureteral obstruction following injection of dextranomer/hyaluronic acid copolymer: an infrequent but relevant complication'. PMID- 22056309 TI - Pediatric chronic orchalgia. AB - INTRODUCTION: Chronic orchalgia, defined as testicular pain lasting > 3 months and interfering with normal activities, is neglected in the pediatric literature. We describe our experience with the evaluation and treatment of pediatric chronic orchalgia patients. MATERIALS AND METHODS: Charts were screened to identify patients meeting the criteria for chronic orchalgia. Charts were further reviewed to record the history and physical exam, diagnostic tests, treatment and outcomes. RESULTS: 65/982 patients met the criteria for chronic orchalgia. Mean age was 13 and mean duration of pain was 8.6 months. Physical exam findings were normal in 46 patients (70%). 59 patients were managed conservatively with resolution (10/59, 17%) or a single visit (36/59, 61%) in 78%. 13/59 (22%) patients showed either minor improvement or no change in symptoms. 5 non responding patients were managed by the anesthesia pain service; 4 received epidurals with or without additional oral pain medications with 3 experiencing significant pain improvement. CONCLUSION: Conservative management of chronic orchalgia allowed symptoms to subside in the majority of cases. We recommend patients be treated with conservative measures for 1-2 months. If this fails, early involvement of the anesthesia pain service can offer treatment modalities such as epidural analgesia. Surgical management in the face of a normal physical exam does not seem to have a role. PMID- 22056310 TI - Intermediate to long-term follow-up indicates low risk of recurrence after double HIT endoscopic treatment for primary vesico-ureteral reflux. PMID- 22056311 TI - [Acute neurological complications after pediatric cardiac surgery: still a long way to go]. AB - INTRODUCTION: There has been an increasing concern over the neurological complications associated with congenital heart disease and cardiac surgery. MATERIAL AND METHODS: We performed a retrospective, case-control, observational review of the postoperative period in the intensive care unit of patients undergoing cardiac surgery over the past 10 years. We selected 2 control patients for each case, matched for surgical complexity. RESULTS: A total of 900 patients were reviewed. We found 38 neurological complications (4.2%), of which 21 (55.3%) were in the peripheral nervous system and 17 (44.7%) in the central nervous system. The complications involving the central nervous system (1.9% of total) consisted of 8 seizures, 4 cerebrovascular accidents, 4 hypoxic-ischemic encephalopathy events, and 1 reversible neurological deficit. At the time of discharge, 35.3% were symptomatic and 17.6% had died. Patients with neurological complications had a longer bypass time (P=.009), longer aortic cross time (P=.012), longer hospitalization in intensive care (P=.001), longer duration of mechanical ventilation (P=.004) and an increased number of days under inotropic support (P=.001). CONCLUSIONS: Our incidence of neurological complications after cardiac surgery is similar to that previously described. Clinical seizures are the most common complication. Central nervous system complications are associated with a higher morbidity and hospitalization time. Units caring for patients with congenital heart disease must implement neurological monitoring during and after cardiac surgery to prevent and to detect these complications earlier. PMID- 22056312 TI - [Does early parenteral protein intake improve extrauterine growth in low birth weight preterms?]. AB - INTRODUCTION: Extrauterine growth restriction affects most premature newborns. Early and higher parenteral protein intake seems to improve postnatal growth and associated comorbidities. We evaluate the impact of a new parenteral nutrition protocol based on early amino acid administration on postnatal growth in premature infants with a birth weight < 1,500 grams. MATERIAL AND METHODS: A case control study in 58 premature newborns with a birth weight < 1,500 grams. In the case group we included 29 preterm neonates who received at least 1.5 g/kg/day parenteral amino acid during the first 24 hours after birth, reaching a maximum dose of 3.5 g/kg/day on the 3(rd)-4(th) day after birth. The control group was formed by 29 preterm neonates for whom protein support began on the 2(nd-)3(rd) day after birth with a dose of 1g/kg/day with lower daily increases than the case group. Growth rates and complications were followed until 28 days of life or discharge from NICU. RESULTS: There were no differences between groups in baseline characteristics. Premature newborns who received higher and earlier doses of proteins had a greater weight gain than the control group, and this difference was statistically significant (423 +/- 138 g vs. 315 +/- 142 g; P=.005). In addition, they had a higher daily weight gain rate (19.4 +/- 3.3 vs. 16.5 +/- 4.8; P=.010) and they regained birth weight earlier (11.5 +/- 3.3 days vs. 14.5 +/- 4.5 days; P=.045). A higher incidence of complications was not observed. CONCLUSIONS: Early and higher amino acid administration improves growth rate in premature neonates with no apparent increase in risks for the patient. PMID- 22056313 TI - Selection for higher gene copy number after different types of plant gene duplications. AB - The evolutionary origins of the multitude of duplicate genes in the plant genomes are still incompletely understood. To gain an appreciation of the potential selective forces acting on these duplicates, we phylogenetically inferred the set of metabolic gene families from 10 flowering plant (angiosperm) genomes. We then compared the metabolic fluxes for these families, predicted using the Arabidopsis thaliana and Sorghum bicolor metabolic networks, with the families' duplication propensities. For duplications produced by both small scale (small-scale duplications) and genome duplication (whole-genome duplications), there is a significant association between the flux and the tendency to duplicate. Following this global analysis, we made a more fine-scale study of the selective constraints observed on plant sodium and phosphate transporters. We find that the different duplication mechanisms give rise to differing selective constraints. However, the exact nature of this pattern varies between the gene families, and we argue that the duplication mechanism alone does not define a duplicated gene's subsequent evolutionary trajectory. Collectively, our results argue for the interplay of history, function, and selection in shaping the duplicate gene evolution in plants. PMID- 22056314 TI - Current knowledge and open issues regarding bevacizumab in gynaecological neoplasms. AB - In the last fifty years the combining of different drugs has progressively improved response and survival rates in gynaecological malignancies. Results are, however, far from being satisfactory. Treatments used in cases of advanced or recurrent disease offer limited results in terms of long-term responses and the urgent need for new drugs has prompted researchers to investigate and propose new therapeutic modalities. One of the most important avenues that are being explored is represented by monoclonal antibodies (MoAb) directed against Vascular Endothelial Growth Factor (VEGF). Several antibodies against this target are now available and Bevacizumab appears to be one of the most promising agents. VEGF has been confirmed as an important therapeutic target in several clinical trials and in multiple disease settings, including gynaecological cancers, for its biological and clinical significance in tumour angiogenesis. The binding and blocking of VEGF growth factor is the basis of tumour growth inhibition, since angiogenesis is essential in the process of tumour growth and progression. Several clinical trials have utilized this agent successfully, either alone or in combination with other drugs. Despite initial concerns, adverse reactions have not been significant with side effects being more tolerable than those associated to conventional chemotherapy. Furthermore, the limited toxicity profile of this, as well as other target therapies, allows it to be combined with cytotoxic drugs without the requirement for a significant dose reduction of the latter. This review outlines the rationale for studying this anti-angiogenetic compound, summarizing the existing and emerging clinical evidence related to the use of Bevacizumab in the treatment of gynaecological malignancies, focusing on its potential benefits and adverse effects. PMID- 22056315 TI - [Welcome to the 64 th congress of the French National Society of Internal Medicine]. PMID- 22056316 TI - Does the Goldilocks Principle apply to calcium release restitution in heart cells? PMID- 22056317 TI - Focal adhesion kinase governs cardiac concentric hypertrophic growth by activating the AKT and mTOR pathways. AB - The heart responds to sustained overload by hypertrophic growth in which the myocytes distinctly thicken or elongate on increases in systolic or diastolic stress. Though potentially adaptive, hypertrophy itself may predispose to cardiac dysfunction in pathological settings. The mechanisms underlying the diverse morphology and outcomes of hypertrophy are uncertain. Here we used a focal adhesion kinase (FAK) cardiac-specific transgenic mice model (FAK-Tg) to explore the function of this non-receptor tyrosine kinase on the regulation of myocyte growth. FAK-Tg mice displayed a phenocopy of concentric cardiac hypertrophy, reflecting the relative thickening of the individual myocytes. Moreover, FAK-Tg mice showed structural, functional and molecular features of a compensated hypertrophic growth, and preserved responses to chronic pressure overload. Mechanistically, FAK overexpression resulted in enhanced myocardial FAK activity, which was proven by treatment with a selective FAK inhibitor to be required for the cardiac hypertrophy in this model. Our results indicate that upregulation of FAK does not affect the activity of Src/ERK1/2 pathway, but stimulated signaling by a cascade that encompasses PI3K, AKT, mTOR, S6K and rpS6. Moreover, inhibition of the mTOR complex by rapamycin extinguished the cardiac hypertrophy of the transgenic FAK mice. These findings uncover a unique role for FAK in regulating the signaling mechanisms that governs the selective myocyte growth in width, likely controlling the activity of PI3K/AKT/mTOR pathway, and suggest that FAK activation could be important for the adaptive response to increases in cardiac afterload. This article is part of a Special Issue entitled "Local Signaling in Myocytes". PMID- 22056318 TI - Epac enhances excitation-transcription coupling in cardiac myocytes. AB - Epac is a guanine nucleotide exchange protein that is directly activated by cAMP, but whose cardiac cellular functions remain unclear. It is important to understand cardiac Epac signaling, because it is activated in parallel to classical cAMP-dependent signaling via protein kinase A. In addition to activating contraction, Ca(2+) is a key cardiac transcription regulator (excitation-transcription coupling). It is unknown how myocyte Ca(2+) signals are decoded in cardiac myocytes to control nuclear transcription. We examine Epac actions on cytosolic ([Ca(2+)](i)) and intranuclear ([Ca(2+)](n)) Ca(2+) homeostasis, focusing on whether Epac alters [Ca(2+)](n) and activates a prohypertrophic program in cardiomyocytes. Adult rat cardiomyocytes, loaded with fluo-3 were viewed by confocal microscopy during electrical field stimulation at 1Hz. Acute Epac activation by 8-pCPT increased Ca(2+) sparks and diastolic [Ca(2+)](i), but decreased systolic [Ca(2+)](i). The effects on diastolic [Ca(2+)](i) and Ca(2+) spark frequency were dependent on phospholipase C (PLC), inositol 1,4,5 triphosphate receptor (IP(3)R) and CaMKII activation. Interestingly, Epac preferentially increased [Ca(2+)](n) during both diastole and systole, correlating with the perinuclear expression pattern of Epac. Moreover, Epac activation induced histone deacetylase 5 (HDAC5) nuclear export, with consequent activation of the prohypertrophic transcription factor MEF2. These data provide the first evidence that the cAMP-binding protein Epac modulates cardiac nuclear Ca(2+) signaling by increasing [Ca(2+)](n) through PLC, IP(3)R and CaMKII activation, and initiates a prohypertrophic program via HDAC5 nuclear export and subsequent activation of the transcription factor MEF2. PMID- 22056319 TI - Early prodromal symptoms can predict future psychosis in familial high-risk youth. AB - BACKGROUND: Efforts to predict psychosis in individuals at high risk for schizophrenia have focused on the identification of sub-threshold clinical criteria and neurobiological markers, including neuropsychological assessment, structural and functional brain imaging, and psychophysiological testing. We sought to evaluate the relative utility of "psychosis-proneness" measures for prospective prediction of psychotic disorders in a group of young relatives at familial risk for schizophrenia. METHODS: We examined the receiver operating characteristics of sub-threshold symptoms in predicting conversion to psychosis in a group of 97 young first- and second- degree relatives of persons with schizophrenia over a 2-year period. Towards this end, we utilized the Structured Interview of prodromal symptoms to derive measures of two of the four Scale of Prodromal Symptoms subscales (positive and disorganized) and the Chapman Magical Ideation and Perceptual Aberration scales. These four measures were, together, taken to reflect a putative index of psychosis-proneness. RESULTS: Eleven of the 97 subjects developed a psychotic disorder over 2 years of follow-up. Seventeen of the 97 subjects tested positive on this index of psychosis-proneness at baseline and of these 10 converted to psychosis. The sensitivity and specificity of the test were 91 percent and 92 percent respectively. The positive predictive value of the test was 59 percent and its negative predictive value was 99 percent. Addition of measures of cognitive or social function to the index decreased its predictive ability, reducing its specificity and/or sensitivity. CONCLUSIONS: A relatively simple set of clinical measures can be utilized to prospectively identify familial high risk individuals who convert to psychosis with high specificity and sensitivity. Implications for the proposed addition of an "attenuated psychosis syndrome" in DSM-5 are discussed. PMID- 22056320 TI - An interactive model of anxiety sensitivity relevant to suicide attempt history and future suicidal ideation. AB - Recent reports of increasing suicide rates among military personnel indicate a need for increased work in understanding processes relevant to suicide risk in the military. Anxiety, along with anxiety-related risk factors have been implicated in suicidality as well as posttraumatic stress disorder (PTSD). One such risk factor, anxiety sensitivity (AS), refers to fear of anxiety-related symptoms. Subfactors of AS, notably the physical and cognitive concerns factors, appear to be relevant to the construct of acquired capability for suicidal behavior, a risk factor for death by suicide postulated by the Interpersonal Psychological Theory of Suicide (Joiner, 2005; Van Orden et al., 2010). Study 1 examined the interaction of AS-cognitive concerns and AS-physical concerns in an outpatient sample with PTSD symptomatology (N = 128). Analyses were consistent with our a priori model and indicated that the interaction of AS-cognitive concerns by AS-physical concerns predicted previous suicide attempt. Specifically, those with high AS-cognitive concerns and low AS-physical concerns were at increased risk for suicide attempt. Study 2 prospectively examined the associations between AS and suicidal ideation in a sample of military cadets undergoing basic training (N = 1081). A similar interaction emerged such that high AS-cognitive and low AS-physical scores at Time 1 significantly predicted suicidal ideation several months later, even after controlling for Time 1 suicidal ideation and psychopathology. These findings suggest that suicide potential may be related to interactions between cognitive risk factors for anxiety among individuals with PTSD symptomatology as well as individuals experiencing stressful life events. PMID- 22056321 TI - Genomic and biological analysis of Grapevine leafroll-associated virus 7 reveals a possible new genus within the family Closteroviridae. AB - Deep sequencing analysis of an asymptomatic grapevine revealed a virome containing five RNA viruses and a viroid. Of these, Grapevine leafroll-associated virus 7 (GLRaV-7), an unassigned closterovirus, was by far the most prominently represented sequence in the analysis. Graft-inoculation of the infection to another grape variety confirmed the lack of the leafroll disease symptoms, even though GLRaV-7 could be detected in the inoculated indicator plants. A 16,496 nucleotide-long genomic sequence of this virus was determined from the deep sequencing data. Its genome architecture and the sequences encoding its nine predicted proteins were compared with those of other closteroviruses. The comparison revealed that two other viruses, Little cherry virus-1 and Cordyline virus-1 formed a well supported phylogenetic cluster with GLRaV-7. PMID- 22056322 TI - The ultrastructure of the ejaculatory duct in the springtail Orchesella villosa (Geoffroy) (Hexapoda, Collembola) and the formation of the spermatophore. AB - The initial part of the ejaculatory duct of Orchesella villosa contains a "valve" and a "sorter" avoiding respectively the reflow and allowing the separation of the secretion for the spermatophore stalk from the sperm fluid. For most of its length, the ejaculatory duct lumen is divided into two parts: in the dorsal part the sperm fluid flows while in the ventral district the secretion for the stalk occurs. Laterally, on both sides of the duct, longitudinal muscle fibers are present. The epithelium of the dorsal region consists of two types of long secretory cells; the most peculiar of them are those provided with extracellular cisterns flowing directly into the duct lumen as it occurs in 1st type of epidermal cells. These cells could be involved in the control of the viscosity of the sperm fluid. The second type of cells produce a secretion probably involved in the formation of the outer coat of the apical sperm droplet. The ventral epithelium consists of short cells contributing to the enrichment of the secretion for the spermatophore stalk and perhaps also to the viscosity of the secretion flowing in the lumen. In the distal part of the ejaculatory duct, the ventral district is provided with a thick layer of muscle fibers and with 3+3 cuticular laminae dividing the lumen into a series of slits through which the secretion of the stalk is squeezed out into filaments. This organization allows the twisting and hardening of these filaments. A drop of sperm fluid is laid on top of the long and rigid spermatophore stalk. PMID- 22056323 TI - Bilateral first rib stress fractures in a female swimmer: a case report. PMID- 22056324 TI - Reverse total shoulder arthroplasty for cuff tear arthropathy: the clinical effect of deltoid lengthening and center of rotation medialization. AB - BACKGROUND: Reverse total shoulder arthroplasty (RSA) for cuff tear arthropathy improves shoulder function and reduces pain. Implant position and soft tissue balancing are important factors to optimize outcome. Tensioning the deltoid and increasing the deltoid moment arm by medializing the center of rotation are biomechanically advantageous. The purpose of this study was to correlate RSA functional outcomes with deltoid lengthening and center of rotation medialization. MATERIALS AND METHODS: This prospective cohort study enrolled 49 consecutive patients who underwent RSA for cuff tear arthropathy. Preoperative and serial postoperative physical examinations, radiographs, and American Shoulder and Elbow Surgeons and Simple Shoulder Test scores were evaluated. Deltoid lengthening and medialization of the center of rotation were measured radiographically and correlated with functional outcome scores, range of motion, and complications. RESULTS: At final follow-up (average, 16 +/- 10 months), 37 of 49 patients (76%) were available for analysis. Deltoid lengthening (average, 21 +/- 10 mm) correlated significantly (P = .002) with superior active forward elevation (average, 144 degrees +/- 19 degrees ). Medialization of the center of rotation (average, 18 +/- 8 mm) did not correlate with active forward elevation or subjective outcomes. Deltoid lengthening that achieved an acromion-greater tuberosity distance exceeding 38 mm had a 90% positive predictive value of obtaining 135 degrees of active forward elevation. Two patients (4%) required revision surgery, and 68% of patients developed scapular notching (average grade, 1.3 +/- 1.2) at final follow-up. CONCLUSION: Deltoid lengthening improves active forward elevation after RSA for cuff tear arthropathy. PMID- 22056325 TI - Rotator cuff injury as a complication of portal placement for superior labrum anterior-posterior repair. AB - BACKGROUND: An accessory trans-rotator cuff portal is commonly used in shoulder arthroscopy, primarily in the repair of SLAP (superior labrum anterior-posterior) lesions. Improper placement of the trans-rotator cuff portal can result in damage to the rotator cuff near its attachment site. METHODS: Six patients were studied, having been referred to our clinic after previous shoulder arthroscopy with SLAP repair. Review of operative notes showed that the rotator cuff had been described as normal in 5 patients and having a mild partial-thickness tear of the supraspinatus in 1 patient at the time of the first surgery. All patients underwent repeat shoulder arthroscopy within 10 to 22 months. RESULTS: All 6 patients were found to have full-thickness rotator cuff tears at the time of the second surgery. The rotator cuff injuries appeared to be associated with portal placement from the previous SLAP repair. All patients underwent rotator cuff repair, and 3 had concomitant revision SLAP repair. All patients had clinical improvement, with a mean preoperative American Shoulder and Elbow Surgeons score of 45.3 and mean postoperative score of 90.5. Mean follow-up was 58.3 months. CONCLUSIONS: Proper placement of a trans-rotator cuff portal should be performed cautiously, traversing the rotator cuff medial to the muscle-tendon junction. This report highlights the potential for injury to the rotator cuff tendons with improper placement of this portal. In patients with persistent pain after previous SLAP repair with a trans-rotator cuff portal technique, rotator cuff injury may be the source of symptoms. Revision surgery with rotator cuff repair can provide improvement. PMID- 22056326 TI - Detection of diarrhoeal pathogens in human faeces using an automated, robotic platform. AB - Infectious diarrhoeal diseases represent a major socio-economic burden to humans, and are linked to a range of pathogens, including viruses, bacteria and protists. The accurate detection of such pathogens is central to control. However, detection often relies on methods that have limited diagnostic sensitivity and specificity. Here, we assessed an automated, robotic platform for the simultaneous detection of eight major pathogens associated with infectious diarrhoea. Genomic DNA samples (n = 167) from faeces from humans with diarrhoea and diagnosed as cryptosporidiosis, and 100 uninfected control subjects, were tested for adenovirus 40/41, norovirus, Clostridium difficile, Campylobacter, Salmonella, Shigella, Cryptosporidium and Giardia by multiplexed-tandem PCR, and also characterized by single-strand conformation polymorphism analysis (SSCP) and selective sequencing. All 167 samples tested positive for Cryptosporidium, five for adenovirus 40/41, four for Campylobacter, three for C. difficile and seven for Shigella spp., with no false positive results for any assay. The automated PCR exhibited a high sensitivity, with <10 individual pathogens being readily detected. The robotic detection platform assessed here represents a sensitive, high-throughput tool for key pathogens linked to infectious diarrhoea in humans. This platform requires little molecular biological expertise and is well suited to various diagnostic facilities and settings. PMID- 22056327 TI - Public health on-call in Scotland: how much experience is sufficient? AB - OBJECTIVES: To quantify the out-of-hours experience obtained by public health trainees in Scotland and to assess whether this is sufficient to meet the Faculty of Public Health guidelines. STUDY DESIGN: Prospective survey. METHODS: All public health trainees in Scotland were invited to participate in a prospective survey of out-of-hours experience. Data were collected from March 2009 to March 2010. The variation in the experience between trainees was compared according to the size, urban/rural mix, and deprivation of the population for which they were responsible. The variation in the experiences gained were then compared to the requirements of the Faculty of Public Health. RESULTS: 18 trainees participated from 6 areas, collecting data on 391 shifts and a total of 276 calls. For every 50 shifts the median number of notifications of probable meningococcus was 3.7 and the median number of chemical incidents and Escherichia coli O157 notifications was 0.0. This variation is difficult to interpret because some trainees collected data for only a short period. The variation between trainees was not significantly related to population size, deprivation or rurality. Pooling the data from all trainees, there was a mean of 2.9 probable meningococcus notifications, 2.4 E coli O157 calls, and 0.3 chemical incident calls per 50 shifts. CONCLUSIONS: There is a large and unpredictable degree of variation in the on-call experience of Scottish trainees. The minimum recommended number of on-call shifts may not be adequate to ensure a high proportion of trainees are prepared for unsupervised on-call. PMID- 22056328 TI - Normal epidermal growth factor receptor signaling is dispensable for bone anabolic effects of parathyroid hormone. AB - Although the bone anabolic properties of intermittent parathyroid hormone (PTH) have long been employed in the treatment of osteoporosis, the molecular mechanisms behind this action remain largely unknown. Previous studies showed that PTH increases the expression and the activity of epidermal growth factor receptor (EGFR) in osteoblasts, and activation of ERK1/2 by PTH in osteoblasts was demonstrated to induce the proteolytical release of EGFR ligands and EGFR transactivation. However, conclusive evidence for an important role of the EGFR system in mediating the anabolic actions of intermittent PTH on bone in vivo is lacking. Here, we evaluated the effects of intermittent PTH on bone in Waved-5 (Wa5) mice which carry an antimorphic Egfr allele whose product acts as a dominant negative receptor. Heterozygous Wa5 females and control littermates received a subcutaneous injection of PTH (80 MUg/kg) or buffer on 5 days per week for 4 weeks. Wa5 mice had slightly lower total bone mineral density (BMD), but normal cancellous bone volume and turnover in the distal femoral metaphysis. The presence of the antimorphic Egfr allele neither influenced the PTH-induced increase in serum osteocalcin nor the increases in distal femoral BMD, cortical thickness, cancellous bone volume, and cancellous bone formation rate. Similarly, the PTH-induced rise in lumbar vertebral BMD was unchanged in Wa5 relative to wild-type mice. Wa5-derived osteoblasts showed considerably lower basal extracellular signal-regulated kinase 1/2 (ERK1/2) activation as compared to control osteoblasts. Whereas activation of ERK1/2 by the EGFR ligand amphiregulin was largely blocked in Wa5 osteoblasts, treatment with PTH induced ERK1/2 activation comparable to that observed in control osteoblasts, relative to baseline levels. Our data indicate that impairment of EGFR signaling does not affect the anabolic action of intermittent PTH on cancellous and cortical bone. PMID- 22056329 TI - Structure of the glycosyltransferase EryCIII in complex with its activating P450 homologue EryCII. AB - In the biosynthesis of the clinically important antibiotic erythromycin D, the glycosyltransferase (GT) EryCIII, in concert with its partner EryCII, attaches a nucleotide-activated sugar to the macrolide scaffold with high specificity. To understand the role of EryCII, we have determined the crystal structure of the EryCIII.EryCII complex at 3.1 A resolution. The structure reveals a heterotetramer with a distinctive, elongated quaternary organization. The EryCIII subunits form an extensive self-complementary dimer interface at the center of the complex, and the EryCII subunits lie on the periphery. EryCII binds in the vicinity of the putative macrolide binding site of EryCIII but does not make direct interactions with this site. Our biophysical and enzymatic data support a model in which EryCII stabilizes EryCIII and also functions as an allosteric activator of the GT. PMID- 22056330 TI - Electrical storm due to managed ventricular pacing. PMID- 22056331 TI - Obstructive sleep apnea: the suffocated atrium? PMID- 22056332 TI - Connexin43 and the regulation of intercalated disc function. PMID- 22056333 TI - Chemical composition and nutritional value of the most widely appreciated cultivated mushrooms: an inter-species comparative study. AB - Herein, it was reported and compared the chemical composition and nutritional value of the most consumed species as fresh cultivated mushrooms: Agaricus bisporus (white and brown mushrooms), Pleurotus ostreatus (oyster mushroom), Pleurotus eryngii (King oyster mushroom), Lentinula edodes (Shiitake) and Flammulina velutipes (Golden needle mushroom). Shiitake revealed the highest levels of macronutrients, unless proteins, as also the highest sugars, tocopherols and PUFA levels, and the lowest SFA content. White and brown mushrooms showed similar macronutrients composition, as also similar values of total sugars, MUFA, PUFA and total tocopherols. Oyster and king oyster mushrooms gave the highest MUFA contents with similar contents in PUFA, MUFA and SFA in both samples. They also revealed similar moisture, ash, carbohydrates and energy values. This study contributes to the elaboration of nutritional databases of the most consumed fungi species worldwide, allowing comparison between them. Moreover it was reported that cultivated and the wild samples of the same species have different chemical composition, including sugars, fatty acids and tocopherols profiles. PMID- 22056334 TI - Pollutant concentrations in placenta. AB - Unborn children are exposed to environmental pollutants via the placenta, and there is a causal relationship between maternal intake of pollutants and fetal exposure. Placental examination is an effective way for acquiring data for estimating fetal exposure. We analyzed the concentrations of 104 congeners of persistent organic pollutants, seven organotin compounds, five heavy metals, and methylmercury in 130 randomly selected placentas. Additionally, we examined similarities between pollutant concentrations by analyzing correlations between their placental concentrations. Our results yield new information for conducting contaminant risk assessments for the prenatal period. Out of the 117 individual persistent organic pollutants or metals assayed, 46 could be detected in more than half of the placentas. Moreover, dichlorodiphenyldichloroethylene (p,p'-DDE) was found in all placentas. The data indicates that fetal exposure to dioxins and furans (PCDD/Fs), polychlorinated biphenyls (PCBs), p,p'-DDE, and methylmercury depends on the mother's parity, and age. We also conclude that sources of the above four pollutants are similar but differ from the sources of polybrominated diphenyl ethers. PMID- 22056335 TI - Evaluation of chemopreventive and cytotoxic effect of lemon seed extracts on human breast cancer (MCF-7) cells. AB - Extracts from lemon seed were investigated for the radical scavenging activity and apoptotic effects in human breast adenocarcinoma (MCF-7) cells and non malignant breast (MCF-12F) cells for the first time. Defatted seed powder was successively extracted with ethyl acetate (EtOAc), acetone, methanol (MeOH), and MeOH:water (80:20). The chemical constituents were identified and quantified by LC-MS and HPLC analysis, respectively. The highest radical scavenging activity of 62.2% and 91.3% was exhibited by MeOH:water (80:20) at 833MUg/mL in 1,1-diphenyl 2-picryl hydrazyl (DPPH) and 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS(+)), respectively. In addition, the MeOH:water (80:20) extract showed the highest (29.1%, P<0.01) inhibition of MCF-7 cells in MTT assay. Treatment of the MeOH:water (80:20) extract induced DNA fragmentation and poly(ADP-ribose) polymerase (PARP) cleavage. Increased levels of Bax and cytosolic cytochrome C and decreased levels of Bcl2 were also observed in MeOH:water (80:20) treated MCF 7 cells. In conclusion, the MeOH:water (80:20) extract from lemon seed has potent antioxidant activity and induces apoptosis in MCF-7 cells, leading to the inhibition of proliferation. These results suggest that aglycones and glucosides of the limonoids and flavonoid present in MeOH:water (80:20) extract may potentially serve as a chemopreventive agent for breast cancer. PMID- 22056336 TI - Differences in the activities of resveratrol and ascorbic acid in protection of ethanol-induced oxidative DNA damage in human peripheral lymphocytes. AB - Previous studies have shown that ethanol induces oxidative DNA damage in human peripheral lymphocytes. In the present study, protective effect of resveratrol and ascorbic acid on ethanol-induced oxidative DNA damage in human peripheral lymphocytes in vitro were comparatively investigated. Pretreatments with resveratrol at 5, 25, and 50MUM, which were in the concentration range of in vitro research, significantly inhibited ethanol-induced oxidative DNA damage in 24h, whereas ascorbic acid showed such DNA protective activity only in 1h. Further study showed that both compounds could directly scavenge hydroxyl radical produced during ethanol metabolism. Resveratrol significantly inhibited ethanol metabolism by regulating alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) mRNA expressions. Moreover, resveratrol also activated the base excision repair (BER) system in mRNA and protein levels in DNA auto repair process. However, ascorbic acid showed no effect on ethanol metabolic pathway and BER system. Thus, the present study provided the first evidence that even though both resveratrol and ascorbic acid are anti-oxidants, they possessed differential mechanisms of action in protection against ethanol-induced oxidative DNA damage in human peripheral lymphocytes. PMID- 22056337 TI - Ascorbic acid ameliorates oxidative damage induced by maternal low-level lead exposure in the hippocampus of rat pups during gestation and lactation. AB - This study was to investigate the effects of ascorbic acid on the hippocampus of suckling rats in the presence of lead (Pb)-induced oxidative stress. Pregnant Sprague-Dawley rats received treatment with drinking water, divided into three groups, as follows: (1) distilled water; (2) 0.2% Pb; (3) 0.2% Pb+ascorbic acid (100mg/kg/day). Rat pups were euthanized at the age of 21days and their brain tissue was examined using light microscopy. Protein levels of Cu/Zn superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD), and catalase (CAT) in the hippocampus were determined by Western blotting. We found a significant decrease in levels of Cu/Zn SOD and Mn SOD among Pb-exposed pups. Ascorbic acid supplementation appeared to negate the decrease in protein levels for Cu/Zn SOD and Mn SOD. In the case of CAT, there was no effect from Pb administration alone and Pb plus ascorbic acid appeared to increase the levels. In histopathology, ascorbic acid decreased the number of damaged cells in cornu ammonis areas CA1, CA3, and the dentate gyrus (DG) in hippocampus. Our results showed that administration of ascorbic acid during pregnancy and lactation could ameliorate some of the oxidative damage induced by Pb exposure in the developing rat hippocampus. PMID- 22056339 TI - In vitro evidence of involvement of the epithelial y+ transporter in beta defensin production on the ocular surface. AB - To analyse the hypothesis as to whether there is a functional relationship between human cationic amino acid transporters (hCATs, y(+) transporter, the main transporter of L-arginine and L-lysine) and human beta-defensin (important components of immune function) production on the ocular surface, arginase and nitrate monoxide synthase (NOS), enzymes that compete for L-arginine, were inhibited by norNOHA (N(omega)-hydroxy-nor-L-arginine) and/or L-NAME (NG-nitro-L arginine methyl ester) in cultured human corneal epithelial cells. In addition, the transport activity of hCAT proteins was inhibited or activated through alpha tocopherol or PMA (phorbol myristate acetate), respectively. Concentrations of the human inducible beta-defensins (hBD) 2 and 3 were determined by ELISA experiments. The basic expression of hBD3 in non-stimulated HCE cells significantly exceeded that of hBD2. Both beta-defensins also differed as to how readily their excretion could be stimulated. HBD2 excretion rate was 3.5 time more by L-NAME, whereas norNOHA had no effect. In contrast, hBD3 excretion was increased by norNOHA by a factor of 1.5 but L-NAME alone had no effect. The excretion of both beta-defensins was increased 3- and 6-fold by combined administration of L-NAME, norNOHA and interleukin (IL)-1beta. Administration of alpha-tocopherol increased hBD2 excretion twofold. No effect was observed for hBD3. With PMA, on the other hand, a reduction in secretion for both beta defensins was observed. These in vitro findings provide evidence of a functional association between CAT proteins and beta-defensins 2 and 3 opening up a new field of research with pharmacological perspectives for treatment of inflammatory diseases such as keratitis or dry eye disease. PMID- 22056338 TI - Dynamics and sensitivity analysis of high-frequency conduction block. AB - The local delivery of extracellular high-frequency stimulation (HFS) has been shown to be a fast acting and quickly reversible method of blocking neural conduction and is currently being pursued for several clinical indications. However, the mechanism for this type of nerve block remains unclear. In this study, we investigate two hypotheses: (1) depolarizing currents promote conduction block via inactivation of sodium channels and (2) the gating dynamics of the fast sodium channel are the primary determinate of minimal blocking frequency. Hypothesis 1 was investigated using a combined modeling and experimental study to investigate the effect of depolarizing and hyperpolarizing currents on high-frequency block. The results of the modeling study show that both depolarizing and hyperpolarizing currents play an important role in conduction block and that the conductance to each of three ionic currents increases relative to resting values during HFS. However, depolarizing currents were found to promote the blocking effect, and hyperpolarizing currents were found to diminish the blocking effect. Inward sodium currents were larger than the sum of the outward currents, resulting in a net depolarization of the nodal membrane. Our experimental results support these findings and closely match results from the equivalent modeling scenario: intra-peritoneal administration of the persistent sodium channel blocker ranolazine resulted in an increase in the amplitude of HFS required to produce conduction block in rats, confirming that depolarizing currents promote the conduction block phenomenon. Hypothesis 2 was investigated using a spectral analysis of the channel gating variables in a single-fiber axon model. The results of this study suggested a relationship between the dynamical properties of specific ion channel gating elements and the contributions of corresponding conductances to block onset. Specifically, we show that the dynamics of the fast sodium inactivation gate are too slow to track the high-frequency changes in membrane potential during HFS, and that the behavior of the fast sodium current was dominated by the low-frequency depolarization of the membrane. As a result, in the blocked state, only 5.4% of nodal sodium channels were found to be in the activatable state in the node closest to the blocking electrode, resulting in conduction block. Moreover, we find that the corner frequency for the persistent sodium channel activation gate corresponds to the frequency below which high-frequency stimuli of arbitrary amplitude are incapable of inducing conduction block. PMID- 22056340 TI - Multiple biomarkers for oxidative stress in patients with brain disorders. PMID- 22056341 TI - Evaluation of possible antioxidant and anticonvulsant effects of the ethyl acetate fraction from Platonia insignis Mart. (Bacuri) on epilepsy models. AB - The aim of present study was to examine the effects of the ethyl acetate fraction (EAF) from Platonia insignis on lipid peroxidation level, nitrite formation, and superoxide dismutase and catalase activities in rat striatum prior to pilocarpine induced seizures as well as to explore its anticonvulsant activity in adult rats prior to pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures. Wistar rats were treated with vehicle, atropine (25mg/kg), EAF (0.1, 1, and 10mg/kg), pilocarpine (400mg/kg, P400 group), PTZ (60 mg/kg, PTZ group), PIC (8 mg/kg, PIC group), atropine+P400, EAF+P400, EAF+PTZ, or EAF+PIC. Significant decreases in number of crossings and rearings were observed in the P400 group. The EAF 10+P400 group also had significant increases in these parameters. In addition, in rats treated with P400, there were significant increases in lipid peroxidation and nitrite levels; however, there were no alterations in SOD and catalase activities. In the EAF 10+P400 group, lipid peroxidation and nitrite levels significantly decreased and SOD and catalase activities significantly increased after pilocarpine-induced seizures. Additionally, effects of the EAF were evaluated in PTZ and PIC models. EAF did not increase the latency to development of convulsions induced with PTZ and PIC at the doses tested. Our findings strongly support the hypothesis that EAF does not have anticonvulsant activity in the different models of epilepsy studied. Our results indicate that in the in vivo model of pilocarpine-induced seizures, EAF has antioxidant activity, but not anticonvulsant properties at the doses tested. PMID- 22056342 TI - The NMDA receptor complex as a therapeutic target in epilepsy: a review. AB - A substantial amount of research has shown that N-methyl-D-aspartate receptors (NMDARs) may play a key role in the pathophysiology of several neurological diseases, including epilepsy. Animal models of epilepsy and clinical studies demonstrate that NMDAR activity and expression can be altered in association with epilepsy and particularly in some specific seizure types. NMDAR antagonists have been shown to have antiepileptic effects in both clinical and preclinical studies. There is some evidence that conventional antiepileptic drugs may also affect NMDAR function. In this review, we describe the evidence for the involvement of NMDARs in the pathophysiology of epilepsy and provide an overview of NMDAR antagonists that have been investigated in clinical trials and animal models of epilepsy. PMID- 22056343 TI - Self-assembly of graphene onto electrospun polyamide 66 nanofibers as transparent conductive thin films. AB - A simple method was developed to assemble graphite oxide (GO) densely onto electrospun (ES) polyamide 66 (PA66) nanofibrous membranes, used as a guide for the deposition of graphene nanosheet (GNS) conductive networks for preparing transparent conductive thin film (TCF). The main advantage of this technique by comparison with previous methods is that graphene does not form a uniform coating, but a percolated conductive network, when guided by PA66 nanofiber templates. A low surface coverage of the transparent substrate by GNS resulted in high transmittance. Polyvinylpyrrolidone-stabilized GO (PVP-GO) was prepared as a modifier for improving the adsorption to the nanofibers. The resulting PVP-GO material could adsorb well on PA66 nanofibers due to stronger hydrogen bonds. Hence, a lower sufficient concentration of PVP-GO (0.050 wt%) solution was required than that for GO solution (0.100 wt%) to fabricate a complete conductive path through a possible enriched adsorption process. For TCF applications, a reduction step is essential because as-deposited GO is non-conductive. In this work, we reduced GO to GNS by a combination of chemical reduction and thermal annealing. The TCF optical transmittance also could be improved after thermal annealing at 350 degrees C above the PA66 melting point. Light scattering by PA66 nanofibers was found as the main cause of reduced transmittance. A fused film, obtained after electrospinning PA66 solution for 120 s, and immersing in 0.050 wt% PVP-GO solution, exhibits a surface resistance of 8.6 * 103 Omega/square, while maintaining 88% light transmittance. PMID- 22056344 TI - High-resolution analysis of Zn(2+) coordination in the alkaline phosphatase superfamily by EXAFS and x-ray crystallography. AB - Comparisons among evolutionarily related enzymes offer opportunities to reveal how structural differences produce different catalytic activities. Two structurally related enzymes, Escherichia coli alkaline phosphatase (AP) and Xanthomonas axonopodis nucleotide pyrophosphatase/phosphodiesterase (NPP), have nearly identical binuclear Zn(2+) catalytic centers but show tremendous differential specificity for hydrolysis of phosphate monoesters or phosphate diesters. To determine if there are differences in Zn(2+) coordination in the two enzymes that might contribute to catalytic specificity, we analyzed both x-ray absorption spectroscopic and x-ray crystallographic data. We report a 1.29-A crystal structure of AP with bound phosphate, allowing evaluation of interactions at the AP metal site with high resolution. To make systematic comparisons between AP and NPP, we measured zinc extended x-ray absorption fine structure for AP and NPP in the free-enzyme forms, with AMP and inorganic phosphate ground-state analogs and with vanadate transition-state analogs. These studies yielded average zinc-ligand distances in AP and NPP free-enzyme forms and ground-state analog forms that were identical within error, suggesting little difference in metal ion coordination among these forms. Upon binding of vanadate to both enzymes, small increases in average metal-ligand distances were observed, consistent with an increased coordination number. Slightly longer increases were observed in NPP relative to AP, which could arise from subtle rearrangements of the active site or differences in the geometry of the bound vanadyl species. Overall, the results suggest that the binuclear Zn(2+) catalytic site remains very similar between AP and NPP during the course of a reaction cycle. PMID- 22056345 TI - Structural and mechanistic characterization of leukocyte-type core 2 beta1,6-N acetylglucosaminyltransferase: a metal-ion-independent GT-A glycosyltransferase. AB - Leukocyte-type core 2 beta1,6-N-acetylglucosaminyltransferase (C2GnT-L) is an inverting, metal-ion-independent glycosyltransferase that catalyzes the formation of mucin-type core 2 O-glycans. C2GnT-L belongs to the GT-A fold, yet it lacks the metal ion binding DXD motif characteristic of other nucleoside disphosphate GT-A fold glycosyltransferases. To shed light on the basis for its metal ion independence, we have solved the X-ray crystal structure (2.3 A resolution) of a mutant form of C2GnT-L (C217S) in complex with the nucleotide sugar product UDP and, using site-directed mutagenesis, examined the roles of R378 and K401 in both substrate binding and catalysis. The structure shows that C2GnT-L exists in an "open" conformation and a "closed" conformation and that, in the latter, R378 and K401 interact with the beta-phosphate moiety of the bound UDP. The two conformations are likely to be important in catalysis, but the conformational changes that lead to their interconversion do not resemble the nucleotide-sugar mediated loop ordering observed in other GT-A glycosyltransferases. R378 and K401 were found to be important in substrate binding and/or catalysis, an observation consistent with the suggestion that they serve the same role played by metal ion in all of the other GT-A glycosyltransferases studied to date. Notably, R378 and K401 appear to function in a manner similar to that of the arginine and lysine residues contained in the RX(4-5)K motif found in the retaining GT-B glycosyltransferases. PMID- 22056346 TI - I-131-MIBG therapies. AB - Metaiodobenzylguanidine (MIBG) is a tracer that selectively targets neuroendocrine cells. On this basis, radiolabeled iodinated-MIBG (I-131-MIBG) has been introduced as a molecular nuclear therapy in the management of neuroendocrine tumors, including neuroblastoma, pheochromocytoma, paraganglioma, neuroendocrine carcinomas, and other rare neuroendocrine tumors. Extensive work has been addressed to develop I-131-MIBG therapy: doses, therapeutic schemes, and efficiency. In this paper, we present an overview on I-131-MIBG therapy, with main focus on different aspects how to perform this treatment. PMID- 22056347 TI - Preparative isolation of alkaloids from Dactylicapnos scandens using pH-zone refining counter-current chromatography by changing the length of the separation column. AB - pH-Zone-refining counter-current chromatography was successfully applied for the preparative separation of alkaloids from Dactylicapnos scandens. The two-phase solvent system was composed of petroleum ether-ethyl acetate-methanol-water (3:7:1:9, v/v), where 20 mM of triethylamine (TEA) was added to the upper phase as a retainer and 5 mM of hydrochloric acid (HCl) to the aqueous phase as an eluter. In this experiment, the apparatus with an adjustable length of the separation column was used for the separation of alkaloids from D. scandens and the resolution of the compounds can be remarkably improved by increasing the length of the separation column. As a result, 70 mg protopin, 30 mg (+) corydine, 120 mg (+) isocorydine and 40 mg (+) glaucine were obtained from 1.0 g of the crude extracts and each with 99.2%, 96.5%, 99.3%, 99.5% purity as determined by HPLC. The chemical structures of these compounds were confirmed by positive ESI MS and (1)H NMR. PMID- 22056348 TI - Clinical outcome of autologous chondrocyte implantation for failed microfracture treatment of full-thickness cartilage defects of the knee joint. AB - BACKGROUND: Although various factors have been identified that influence outcome after autologous chondrocyte implantation (ACI), the relevance of prior treatment of the cartilage defect and its effect concerning the outcome of second-line ACI have not been evaluated to a full extent. HYPOTHESIS: Autologous chondrocyte implantation used as a second-line treatment after failed arthroscopic microfracturing is associated with a higher failure rate and inferior clinical results compared with ACI as a first-line treatment. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 28 patients with isolated cartilage defects at the knee joint were treated with ACI after microfracture as a first line treatment had failed (failure defined as the necessity of reintervention). These patients were assigned to group A and compared with a matched-pair cohort of patients of identical age, defect size, and defect location (group B) in which ACI was used as a first-line treatment. Failure rates in both groups were assessed. Postoperative knee status was evaluated with the International Knee Documentation Committee (IKDC) score and Knee injury and Osteoarthritis Outcome Score (KOOS), and sporting activity was assessed by use of the Activity Rating Scale. Mean follow-up times were 48.0 months (range, 15.1-75.1 months) in group A and 41.4 months (range, 15.4-83.6 months) in group B. Differences between groups A and B were analyzed by Student t test. RESULTS: Group A had significantly greater failure rates (7 of 28 patients) in comparison with group B (1 of 28 patients; P = .0241). Mean (SD) postoperative IKDC scores revealed 58.4 (22.4) points in group A with a trend toward higher score results (69.0 [19.1] points) for patients in group B (P = .0583). Significantly different results were obtained for KOOS pain and activity of daily living subscales, whereas the remaining KOOS subscales did not show significant differences. Despite the significantly higher failure rate observed in group A, those patients did not participate in fewer activities or perform physical activity less frequently or at a lower intensity. CONCLUSION: Autologous chondrocyte implantation after failed microfracturing appears to be associated with a significantly higher failure rate and inferior clinical outcome when compared with ACI as a first-line treatment. PMID- 22056349 TI - The last mile: taking the final steps in preventing pediatric pharmaceutical poisonings. PMID- 22056350 TI - Respiratory function monitor guidance of mask ventilation in the delivery room: a feasibility study. AB - OBJECTIVE: To investigate whether using a respiratory function monitor (RFM) during mask resuscitation of preterm infants reduces face mask leak and improves tidal volume (V(T)). STUDY DESIGN: Infants receiving mask resuscitation were randomized to have the display of an RFM (airway pressure, flow, and V(T) waves) either visible or masked. RESULT: Twenty-six infants had the RFM visible, and 23 had the RFM masked. The median mask leak was 37% (IQR, 21%-54%) in the visible RFM group and 54% (IQR, 37%-82%) in the masked RFM group (P = .01). Mask repositioning was done in 19 infants (73%) of the visible group and in 6 infants (26%) of the masked group (P = .001). The median expired V(T) was similar in the 2 groups. Oxygen was provided to 61% of the visible RFM group and 87% of the RFM masked group (P = .044). Continuous positive airway pressure use was greater in the visible RFM group (73% vs 43%; P = .035). Intubation in the delivery room was done in 21% of the visible group and in 57% of the masked group (P = .035). CONCLUSION: Using an RFM was associated with significantly less mask leak, more mask adjustments, and a lower rate of excessive V(T). PMID- 22056351 TI - Oral ibuprofen for the treatment of patent ductus arteriosus: further clarification. PMID- 22056352 TI - Predictors of blood pressure and its control in pediatric patients receiving dialysis. AB - OBJECTIVE: To evaluate and characterize the degree of blood pressure (BP) control in children on chronic dialysis and to identify significant predictors of hypertension and BP control in these patients. STUDY DESIGN: Linear and logistic regression models were used to examine trends in BP and BP control in a cross sectional sample of patients on chronic dialysis aged 1-21 years enrolled in the North American Pediatric Renal Trials and Collaborative Studies registry from 1992-2008. RESULTS: At 6 months after dialysis initiation, 67.9% of patients had uncontrolled or untreated hypertension, and 57.8% were prescribed antihypertensive medications. More recent year of dialysis initiation was associated with a higher use of antihypertensive medication and lower systolic BP and diastolic BP z scores (P < .001) measured over time from 6 months to 3 years post dialysis initiation. Other factors associated with higher BP included black race, glomerular disease, younger age, hemodialysis (systolic BP only), and antihypertensive use. There were significant differences in BP control by dialysis modality and disease etiology, with patients on hemodialysis or those with glomerular diseases having the highest percentage of uncontrolled hypertension. CONCLUSIONS: Despite widespread antihypertensive use, many pediatric patients on dialysis are at risk for untreated or uncontrolled hypertension. Additional efforts are needed to improve management of hypertension in these children. PMID- 22056353 TI - Baroreflex sensitivity is associated with sleep-related breathing problems in adolescents. AB - OBJECTIVES: To examine the relationship between sleep-related breathing problems (SRBPs) and baroreflex sensitivity (BRS) among adolescents and assesses whether body mass influences this relationship. STUDY DESIGN: SRBPs were assessed in 106 adolescents aged 11-14 years using the Pediatric Sleep Questionnaire. Body mass index (BMI) was calculated, and 5 minutes of continuous beat-to-beat blood pressure (Finapres) and R-R interval were recorded (standard electrocardiogram) after 15 minutes of supine rest. Spectral indices were computed using fast Fourier transform, and transfer function analysis was used to compute BRS. RESULTS: Regression analyses indicate an interaction between BMI and SRBPs (b= .151, P=.015) on BRS. Graphing the interaction showed that those with higher SRBP scores had lower BRS but that this effect was stronger for those with higher BMI. CONCLUSIONS: Adolescents with elevated SRBP scores had lower BRS. In addition, higher BMI amplified the risk of higher SRBP scores on BRS. PMID- 22056354 TI - Intestinal inflammatory cytokine response in relation to tumorigenesis in the Apc(Min/+) mouse. AB - The etiology of colon cancer is a complex phenomenon that involves both genetic and environmental factors. However, only about 20% have a familial basis with the largest fraction being attributed to environmental causes that can lead to chronic inflammation. While the link between inflammation and colon cancer is well established, the temporal sequence of the inflammatory response in relation to tumorigenesis has not been characterized. We examined the timing and magnitude of the intestinal inflammatory cytokine response in relation to tumorigenesis in the Apc(Min/+) mouse. Apc(Min/+) mice and wildtype mice were sacrificed at one of 4 time-points: 8, 12, 16, and 20 weeks of age. Intestinal tissue was analyzed for polyp burden (sections 1, 4 and 5) and mRNA expression and protein concentration of MCP-1, IL-1beta, IL-6 and TNF-alpha (sections 2 and 3). The results show that polyp burden was increased at 12, 16 and 20 weeks compared to 8 weeks (P<0.05). Gene expression (mRNA) of MCP-1, IL-1beta, IL-6 and TNF-alpha was increased in sections 2 and 3 starting at week 12 (P<0.05), with further increases in MCP-1, IL-1beta and IL-6 at 16 weeks (P<0.05). Protein concentration for these cytokines followed a similar pattern in section 3. Similarly, circulating MCP-1 was increased at 12 weeks (P<0.05) and then again at 20 weeks (P<0.05). In general, overall polyp number and abundance of large polyps were significantly correlated with the inflammatory cytokine response providing further support for a relationship between polyp progression and these markers. These data confirm the association between intestinal cytokines and tumorigenesis in the Apc(Min/+) mouse and provide new information on the timing and magnitude of this response in relation to polyp development. These findings may lead to the development of inflammatory mediators as important biomarkers for colon cancer progression. Further, these data may be relevant in the design of future investigations of therapeutic interventions to effectively target inflammatory processes in rodent models. PMID- 22056356 TI - Three-component intraperitoneal mesh fixation for laparoscopic repair of anterior parasternal costodiaphragmatic hernias. PMID- 22056355 TI - Decision making about surgery for early-stage breast cancer. AB - BACKGROUND: Practice variation in breast cancer surgery has raised concerns about the quality of treatment decisions. We sought to evaluate the quality of decisions about surgery for early-stage breast cancer by measuring patient knowledge, concordance between goals and treatments, and involvement in decisions. STUDY DESIGN: A mailed survey of stage I/II breast cancer survivors was conducted at 4 sites. The Decision Quality Instrument measured knowledge, goals, and involvement in decisions. A multivariable logistic regression model of treatment was developed. The model-predicted probability of mastectomy was compared with treatment received for each patient. Concordance was defined as having mastectomy and predicted probability >0.5 or partial mastectomy and predicted probability <0.5. Frequency of discussion about partial mastectomy was compared with discussion about mastectomy using chi-square tests. RESULTS: Four hundred and forty patients participated (59% response rate). Mean overall knowledge was 52.7%; 45.9% knew that local recurrence risk is higher after breast conservation and 55.7% knew that survival is equivalent for the 2 options. Most participants (89.0%) had treatment concordant with their goals. Participants preferring mastectomy had lower concordance (80.5%) than those preferring partial mastectomy (92.6%; p = 0.001). Participants reported more frequent discussion of partial mastectomy and its advantages than of mastectomy, and 48.6% reported being asked their preference. CONCLUSIONS: Breast cancer survivors had major knowledge deficits, and those preferring mastectomy were less likely to have treatment concordant with goals. Patients perceived that discussions focused on partial mastectomy, and many were not asked their preference. Improvements in the quality of decisions about breast cancer surgery are needed. PMID- 22056357 TI - Two tall poppies and the discovery of Helicobacter pylori. PMID- 22056358 TI - Ccdc85c encoding a protein at apical junctions of radial glia is disrupted in hemorrhagic hydrocephalus (hhy) mice. AB - Cortical heterotopia, a malformation of the developing cortex, are a major cause of epilepsy and mental retardation in humans. Hemorrhagic hydrocephalus (hhy) mutation on mouse chromosome 12 results in subcortical heterotopia and nonobstructive hydrocephalus with frequent brain hemorrhage. Here, we show that coiled-coil domain-containing 85C (Ccdc85c), consisting of 6 exons that encode a 420 amino acid protein, is disrupted by replacement of a 3.2-kb sequence, including exon 2 in Ccdc85c by a 1.5-kb retrotransposon-like repeat sequence in the hhy mutant. Immunoreactivity to Ccdc85C was detected predominantly at the apical junctions of radial glia in the wall of lateral ventricles of the developing brain. In the hhy brain at embryonic (E) day 18 (E18), radial glial demise followed by agenesis of the ependymal layer lining the neonatal cortex and accumulation of neuronal specific nuclear protein (NeuN)-positive postmigratory neurons in the subcortical area occurred. Accumulation of E15-born, but not of E13-born, 5-bromo-2'-deoxyuridine labeled neurons expressing special AT-rich sequence binding protein 2 was detected in both heterotopia and the superficial layers of the hhy neocortex at postnatal day 7. Ccdc85c deficiency permitted radial scattering of paired box gene 6-positive neural progenitors in the ventricular zone, likely resulting in reduced self-renewal of the progenitors in the developing hhy cortex. These findings indicate an important role of Ccdc85C in cortical development and provide a mouse model to study pathogenesis of subcortical heterotopia and hydrocephalus. PMID- 22056359 TI - Mitochondrial genome instability and ROS enhance intestinal tumorigenesis in APC(Min/+) mice. AB - Alterations in mitochondrial oxidative phosphorylation have long been documented in tumors. Other types of mitochondrial dysfunction, including altered reactive oxygen species (ROS) production and apoptosis, also can contribute to tumorigenesis and cancer phenotypes. Furthermore, mutation and altered amounts of mitochondrial DNA (mtDNA) have been observed in cancer cells. However, how mtDNA instability per se contributes to cancer remains largely undetermined. Mitochondrial transcription factor A (TFAM) is required for expression and maintenance of mtDNA. Tfam heterozygous knock-out (Tfam(+/-)) mice show mild mtDNA depletion, but have no overt phenotypes. We show that Tfam(+/-) mouse cells and tissues not only possess less mtDNA but also increased oxidative mtDNA damage. Crossing Tfam(+/-) mice to the adenomatous polyposis coli multiple intestinal neoplasia (APC(Min/+)) mouse cancer model revealed that mtDNA instability increases tumor number and growth in the small intestine. This was not a result of enhancement of Wnt/beta-catenin signaling, but rather appears to involve a propensity for increased mitochondrial ROS production. Direct involvement of mitochondrial ROS in intestinal tumorigenesis was shown by crossing APC(Min/+) mice to those that have catalase targeted to mitochondria, which resulted in a significant reduction in tumorigenesis in the colon. Thus, mitochondrial genome instability and ROS enhance intestinal tumorigenesis and Tfam(+/-) mice are a relevant model to address the role of mtDNA instability in disease states in which mitochondrial dysfunction is implicated, such as cancer, neurodegeneration, and aging. PMID- 22056361 TI - Oxygen modulates the response of first-trimester trophoblasts to hyperglycemia. AB - Pregestational diabetes retards early embryonic growth. Placental and fetal growth are closely associated, suggesting that placental growth is also impaired. During the first trimester of gestation, oxygen tension rises steeply, leading to excessive production of reactive oxygen species (ROS), which is exacerbated in diabetes and may affect placental development. We hypothesized that oxygen modifies hyperglycemic effects on ROS formation, resulting in decreased first trimester trophoblast growth. This was tested using a first trimester trophoblast derived cell line (ACH-3P). Normoglycemia did not alter ACH-3P proliferation at 2.5%, 8%, and 21% oxygen. Hyperglycemic conditions for up to 3 days reduced cell number by 65% and resulted in cell cycle (G(1)- and S-phase) changes but only at 21% oxygen. Proliferation reduction could be partially restored by an inhibitor of mitogen-activated protein kinase (MAPK) ERK1/2 but not of Akt/PkB. Intracellular ROS elevation under hyperglycemia was oxygen independent, whereas mitochondrial superoxide levels were enhanced under hyperglycemia only at 21% oxygen. Intervention to modulate cytosolic and mitochondrial ROS, using ROS formation inducers and inhibitors, did not alter cell growth under hyperglycemia at 21% oxygen. The combination of hyperglycemia and high oxygen levels (21%) reduces proliferation of human first-trimester trophoblasts in a ROS-independent manner involving MAPK. This may account for reduced placental growth and, therefore, also for embryonic growth during the first-trimester pregestational diabetic pregnancies when the oxygen tension increases. PMID- 22056360 TI - Epigallocatechin-3-gallate ameliorates experimental autoimmune encephalomyelitis by altering balance among CD4+ T-cell subsets. AB - The green tea component epigallocatechin-3-gallate (EGCG) may be beneficial in autoimmune diseases; however, the underlying mechanisms are not well understood. In this study, we determined the effect of EGCG on the development of experimental autoimmune encephalomyelitis, an animal model for human multiple sclerosis, and the underlying mechanisms. Female C57BL/6 mice were fed EGCG (0%, 0.15%, 0.3%, and 0.6% in diet) for 30 days and then immunized with specific antigen myelin oligodendrocyte glycoprotein 35-55. EGCG dose dependently attenuated clinical symptoms and pathological features (leukocyte infiltration and demyelination) in the central nervous system and inhibited antigen-specific T cell proliferation and delayed-type hypersensitivity skin response. We further showed that EGCG reduced production of interferon-gamma, IL-17, IL-6, IL-1beta, and tumor necrosis factor-alpha; decreased types 1 and 17 helper T cells (Th1 and Th17, respectively); and increased regulatory T-cell populations in lymph nodes, the spleen, and the central nervous system. Moreover, EGCG inhibited expression of transcription factors T-box expressed in T cells and retinoid-related orphan receptor-gammat, the specific transcription factor for Th1 and Th17 differentiation, respectively; the plasma levels of intercellular adhesion molecule 1; and CCR6 expression in CD4(+) T cells. These results indicate that EGCG may attenuate experimental autoimmune encephalomyelitis autoimmune response by inhibiting immune cell infiltration and modulating the balance among pro- and anti-autoimmune CD4(+) T-cell subsets. Thus, we identified a novel mechanism that underlies EGCG's beneficial effect in autoimmune disease. PMID- 22056362 TI - Localization in the vagal ganglia of calcitonin gene-related peptide- and calretinin-immunoreactive neurons that innervate the cervical and the subdiaphragmatic esophagus of the rat. AB - We have determined the localization of calcitonin gene-related peptide immunoreactive (CGRP-ir) and calretinin-ir neurons in the vagal ganglia that innervate the cervical or subdiaphragmatic esophagus. Many CGRP-ir neurons were found exclusively in the jugular ganglion located in the cranial cavity. Calretinin-ir neurons were distributed throughout the vagal ganglia. Injection of Fluorogold into the cervical esophagus resulted in many Fluorogold-labeled neurons in the jugular and nodose ganglia. Injection of Fluorogold into the subdiaphragmatic esophagus resulted in many Fluorogold-labeled neurons, with most in the nodose ganglion. In the case of Fluorogold injection into the cervical esophagus, double-labeling combining immunohistochemistry and retrograde tracing showed that about 40% of the Fluorogold-labeled neurons in the jugular ganglion express CGRP-like immunoreactivity, and about 20% of the Fluorogold-labeled neurons in both the jugular and nodose ganglia express calretinin-like immunoreactivity. In the case of injection into the subdiaphragmatic esophagus, only a few Fluorogold-labeled neurons express CGRP-like immunoreactivity or calretinin-like immunoreactivity in the vagal ganglia. These results indicate that the cervical esophagus receives projections from many CGRP-ir neurons in the jugular ganglion and from calretinin-ir neurons in the jugular and nodose ganglia, while the subdiaphragmatic esophagus receives projections from only a few CGRP-ir and calretinin-ir neurons in the vagal ganglia. PMID- 22056364 TI - An analysis, systematic review, and meta-analysis of the perioperative mortality after neoadjuvant therapy and pneumonectomy for non-small cell lung cancer. AB - OBJECTIVE: Pneumonectomy after neoadjuvant therapy remains controversial. METHODS: A systematic PubMed search was performed for original articles from 1990 through 2010 describing pneumonectomy after neoadjuvant therapy. Specific data on 30-day and 90-day perioperative mortalities were abstracted from these articles. Meta-analysis compared 30-day mortality between right and left pneumonectomy with a fixed-effects model. Comparison between 30-day and 90-day mortalities was also performed. RESULTS: The search strategy yielded 27 studies. Overall, 30-day and 90-day perioperative mortalities were 7% and 12%, respectively. Among 15 studies providing side-specific 30-day mortality, cumulative mortalities were 11% and 5% for right and left pneumonectomies, respectively. In the meta-analysis that included 10 studies, 30-day mortality for right pneumonectomy remained greater than for left pneumonectomy (odds ratio, 1.97; 95% confidence interval, 1.11 3.49; P = .02). Among 6 studies providing side-specific 90-day mortality, cumulative mortalities were 20% and 9% for right and left pneumonectomies, respectively. In the meta-analysis that included 4 studies, 90-day mortality for right pneumonectomy was greater than for left pneumonectomy (odds ratio, 2.01; 95% confidence interval, 1.09-3.72; P = .03). Among 11 studies providing both 30 day and 90-day mortalities, mortality difference was 5% (95% confidence interval, 4%-7%, P < .0001). Pulmonary complications were the most common cause of 30-day and 90-day deaths. CONCLUSIONS: Right pneumonectomy is associated with significantly higher 30-day and 90-day mortalities after neoadjuvant therapy than left pneumonectomy. Also, 90-day mortality for all pneumonectomies appears to be greater than expected, suggesting that the 30-day mortality figure may inadequately assess the perioperative mortality. PMID- 22056365 TI - Progressive induction of left ventricular pressure overload in a large animal model elicits myocardial remodeling and a unique matrix signature. AB - OBJECTIVE: Patients with severe left ventricular pressure overload secondary to aortic stenosis can present with signs and symptoms of heart failure despite normal left ventricular ejection fraction. This process occurs, at least in part, as a result of left ventricular pressure overload-induced extracellular matrix remodeling that promulgates increased left ventricular stiffness and impaired diastolic function. However, the determinants that drive extracellular matrix remodeling in this form of left ventricular pressure overload remain to be fully defined. METHODS: Left ventricular pressure overload was induced in mature pigs (n = 15) by progressive ascending aortic cuff inflation (once per week for 4 weeks), whereby left ventricular mass, left ventricular ejection fraction, and regional myocardial stiffness (rK(m)) were compared with referent controls (n = 12). Determinants of extracellular matrix remodeling were assessed by measuring levels of mRNA expression for fibrillar collagens, matrix metalloproteinases, and tissue inhibitors of matrix metalloproteinase 1 and 4. RESULTS: With left ventricular pressure overload, left ventricular mass and rK(m) increased by 2- and 3-fold, respectively, compared with control, with no change in left ventricular ejection fraction. Left ventricular myocardial collagen increased approximately 2-fold, which was accompanied by reduced solubility (ie, increased cross-linking) with left ventricular pressure overload, but mRNA expression for fibrillar collagen and matrix metalloproteinases remained relatively unchanged. In contrast, a robust increase in mRNA expression for tissue inhibitors of matrix metalloproteinase-1 and 4 occurred with left ventricular pressure overload. CONCLUSIONS: In a progressive model of left ventricular pressure overload, which recapitulates the phenotype of aortic stenosis, increased extracellular matrix accumulation and subsequently increased myocardial stiffness were not due to increased fibrillar collagen expression but rather to determinants of post translational control that included increased collagen stability (thereby resistant to matrix metalloproteinase degradation) and increased endogenous matrix metalloproteinase inhibition. Targeting these extracellular matrix post translational events with left ventricular pressure overload may hold both diagnostic and therapeutic relevance. PMID- 22056367 TI - Long-term importance of right ventricular outflow tract patch function in patients with pulmonary regurgitation. AB - OBJECTIVE: Chronic pulmonary regurgitation (PR) has deleterious effects on right ventricular (RV) function in repaired tetralogy of Fallot (ToF). However, there are little data regarding right ventricular outflow tract (RVOT) contractile dysfunction in response to chronic PR and on both RV and LV volumes and function. METHODS: We retrospectively identified consecutive patients with PR who were referred for magnetic resonance imaging quantification of "free PR" detected on echocardiography between 2003 and 2008. Patients had ToF and a transannular patch procedure (n = 30, 25.1 +/- 1.2 years) or PR resulting from valvar pulmonary stenosis treated with surgical or percutaneous valvotomy (n = 30, 26.6 +/- 1.8 years). RESULTS: The ToF and the PS groups were well matched for age at scan, age at repair surgery in ToF or initial valvotomy in PS, duration of exposure to PR, body surface area, heart rate, PR fraction, net forward pulmonary artery flow, and main and branch pulmonary artery dimensions. Severe PR fractions were identified in both groups (ToF: 40% +/- 1% vs PS: 37% +/- 2%, P = .2). Indexed RV and LV end-diastolic volumes were similar for both ToF and PS groups (RV end diastolic volume index: 137 +/- 6 mL/m(2) vs 128 +/- 5 mL/m(2), P = .2, and LV end-diastolic volume index: 72 +/- 2 mL/m(2) vs 67 +/- 2 mL/m(2), P = .1, respectively). RV mass was also similar between groups (95 +/- 5 g vs 81 +/- 6 g, respectively, P = .08). However, indexed RV and LV end-systolic volumes were consistently higher in ToF when compared with PS (RV end-systolic volume index: 70 +/- 5 mL/m(2) vs 54 +/- 3 mL/m(2), P < .01, and LV end-systolic volume index: 29 +/- 1 mL/m(2) vs 22 +/- 1 mL/m(2), P < .01, respectively). These changes were reflected in lower biventricular systolic function in patients with ToF when compared with PS (RV ejection fraction: 52% +/- 1.5% vs 59% +/- 1%, P < .001, and LV ejection fraction: 61% +/- 1% vs 67 +/- 1%, P < .001, respectively). Although RV transannular plane systolic excursion was not significantly different between the groups (P = .86), the RV outflow tract was considered contractile in only 50% of patients with ToF compared with 93% of patients with PS (P = .0004). RV volumes and function were similar when only patients with contractile RV outflow tracts were compared. CONCLUSIONS: RV outflow tract patch dysfunction in repaired ToF is responsible for higher end-systolic volumes and thus lower global measures of ventricular systolic function. These findings were not evident in cases of PS treated with valvotomy with comparable amount of PR. These observations highlight the importance of the initial repair surgery in ToF for late outcomes. PMID- 22056368 TI - Aortocarotid bypass at the time of central aortic repair for type A acute aortic dissections. PMID- 22056369 TI - Randomized comparison of awake nonresectional versus nonawake resectional lung volume reduction surgery. AB - OBJECTIVE: The study objective was to assess in a randomized controlled study (NCT00566839) the comparative results of awake nonresectional or nonawake resectional lung volume reduction surgery. METHOD: Sixty-three patients were randomly assigned by computer to receive unilateral video-assisted thoracic surgery lung volume reduction surgery by a nonresectional technique performed through epidural anesthesia in 32 awake patients (awake group) or the standard resectional technique performed through general anesthesia in 31 patients (control group). Primary outcomes were hospital stay and changes in forced expiratory volume in 1 second. During follow-up, the need of contralateral treatment because of loss of postoperative benefit was considered a failure event as death. RESULTS: Intergroup comparisons (awake vs control) showed no difference in gender, age, and body mass index. Hospital stay was shorter in the awake group (6 vs 7.5 days, P = .04) with 21 versus 10 patients discharged within 6 days (P = .01). At 6 months, forced expiratory volume in 1 second improved significantly in both study groups (0.28 vs 0.29 L) with no intergroup difference (P = .79). In both groups, forced expiratory volume in 1 second improvements lasted more than 24 months. At 36 months, freedom from contralateral treatment was 55% versus 50% (P = .5) and survival was 81% versus 87% (P = .5). CONCLUSIONS: In this randomized study, awake nonresectional lung volume reduction surgery resulted in significantly shorter hospital stay than the nonawake procedure. There were no differences between study groups in physiologic improvements, freedom from contralateral treatment, and survival. We speculate that compared with the nonawake procedure, awake lung volume reduction surgery can offer similar clinical benefit but a faster postoperative recovery. PMID- 22056370 TI - 4-nonylphenol triggers apoptosis and affects 17-beta-estradiol receptors in calvarial osteoblasts. AB - The present research examines the effects of 4-nonylphenol (4-NP) on mouse primary calvarial osteoblasts (COBs). Incubation of the cells with 4-NP at 10( 5)M and 10(-6)M striking decreased osteoblasts viability and phosphatidylserine (PS) exposure, measured by Annexin V, was greatly enhanced. In addition, an up regulation of Bax/Bcl2 ratio with a drop in DeltaPsim and an increase of cleaved caspase 9 and 3 was found, suggesting that the alkylphenol induced osteoblast death via the mitochondrial-dependent apoptotic pathway. Interestingly, treatment with 4-NP was also able to increase cleaved caspase 8 in parallel with the truncated active Bid (t-Bid) suggesting that 4-NP-mediated apoptosis depends on cross talk between the extrinsic and intrinsic pathways. It is of relevance, that the apoptotic effects of 4-NP overcame 17-beta-Estradiol (17-beta E(2)) induced survival on osteoblasts. Also, the alkylphenol interfered with 17-beta E(2) regulated estrogen receptors expression. PMID- 22056371 TI - Exogenous intravascular nitric oxide enhances ventricular function after hemodilution with plasma expander. AB - AIMS: This study evaluated the hypothesis that exogenous nitric oxide (NO) supplementation during acute hemodilution with plasma expander (PE) provides beneficial effects on cardiac function. MAIN METHODS: Acute hemodilution in golden Syrian hamsters was induced by a 40% of blood volume exchange with dextran 70 kDa. Intravascular NO supplementation after hemodilution was accomplished with a NO donor, diethylenetriamine NONOate (DETA NONOate). The test group was treated with DETA NONOate, while the control group received only vehicle. Left ventricular cardiac function was studied using pressure-volume measurements obtained with a miniaturized conductance catheter. KEY FINDINGS: Cardiac output increased to 122+/-5% and 107+/-1% of the baseline in the group treated with NO donor and the vehicle group, respectively. Stroke work per stroke volume (SW/SV) after hemodilution reduced to 90% of the baseline and the NO donor significantly reduced SW/SV compared to the vehicle. The minimum rate of pressure change (dP/dt(min)) was significantly lower in animals treated with the NO donor compared to vehicle treated animals. Systemic vascular resistance (SVR) decreased to 62+/-5% of the baseline in the NO donor group whereas the vehicle group SVR decreased to 83+/-5% of the baseline. Using intravital microscopy analysis of microvessel in the dorsal skinfold window chamber, we established that the NO donor group induced significant vasodilation compared to the vehicle group. SIGNIFICANCE: NO supplementation in an acute hemodilution with PE has beneficial effects on cardiac performance. However, the NO supplementation effects with a NO donor are dose-independent and short-lasting. PMID- 22056372 TI - Insulin attenuates the acquisition and expression of ethanol-induced locomotor sensitization in DBA/2J mice. AB - AIM: Ethanol-induced locomotor sensitization is a behavioral manifestation of physiological responses to repeated ethanol exposures. While ethanol exerts direct effects on multiple neurotransmitter systems in the brain, ethanol-induced changes in metabolic state, including acute hyperglycemia and inhibition of insulin signaling, also have plausible roles in the expression of ethanol-related behaviors through direct and indirect effects on brain function. The current experiments examined whether insulin administration or the resultant hypoglycemia might attenuate the development of sensitization to the locomotor stimulant effect of ethanol. MAIN METHODS: Male and female DBA/2J mice received daily injections of 5 or 10 IU/kg insulin before or after a stimulating dose of ethanol and subsequent testing in an automated activity monitor. Blood glucose levels were determined upon the completion of the experiments. KEY FINDINGS: Insulin injected prior to ethanol blunted the acute stimulant response as well as the acquisition and expression of locomotor sensitization, while insulin given after ethanol did not affect the development of the sensitized response. In a separate experiment, mice given glucose concurrently with insulin developed ethanol induced locomotor sensitization normally. SIGNIFICANCE: These experiments suggest that insulin attenuates the development of ethanol-induced locomotor sensitization, and that blood glucose levels can largely account for this effect. Further studies of the role of ethanol-induced metabolic states should provide novel information on the expression of ethanol-related behaviors. PMID- 22056373 TI - DA-1229, a novel and potent DPP4 inhibitor, improves insulin resistance and delays the onset of diabetes. AB - AIM: To characterize the pharmacodynamic profile of DA-1229, a novel dipeptidyl peptidase (DPP) 4 inhibitor. MAIN METHODS: Enzyme inhibition assays against DPP4, DPP8 and DPP9. Antidiabetic effects of DA-1229 in HF-DIO mice and young db/db mice. KEY FINDINGS: DA-1229 was shown to potently inhibit the DPP4 enzyme in human and murine soluble forms and the human membrane-bound form with IC(50) values of 0.98, 3.59 and 1.26 nM, respectively. As a reversible and competitive inhibitor, DA-1229 was more selective to human DPP4 (6000-fold) than to human DPP8 and DPP9. DA-1229 (0.1-3mg/kg) dose-dependently inhibited plasma DPP4 activity, leading to increased levels of plasma GLP-1 and insulin, and thereby lowering blood glucose levels in mice. In high fat diet-fed (HF) mice, a single oral dose of 100mg/kg of DA-1229 reduced plasma DPP4 activity by over 80% during a 24h period. Long-term treatment with DA-1229 for 8 weeks revealed significant improvements in glucose intolerance and insulin resistance, accompanied by significant body weight reduction. However, it remains unclear whether there is a direct causal relationship between DPP4 inhibition and body weight reduction. In young db/db mice, the DA-1229 treatment significantly reduced blood glucose excursions for the first 2 weeks, resulting in significantly lower levels of HbA1c at the end of the study. Furthermore, the pancreatic insulin content of the treatment group was significantly higher than that of the db/db control. SIGNIFICANCE: DA-1229 as a novel and selective DPP4 inhibitor improves the insulin sensitivity in HF mice and delays the onset of diabetes in young db/db mice. PMID- 22056374 TI - Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells. AB - AIMS: Endothelial dysfunction is a common manifestation of chronic kidney disease (CKD). The protein-bound uremic toxins have emerged as important factors associated with cardiovascular disease and the outcome of CKD. The effect of indoxyl sulfate (IS) on endothelial cells remains unclear. MAIN METHODS: Human umbilical endothelial cells (HUVEC) were incubated using IS at two concentrations: 100 MUM and 1000 MUM over two periods of time: 16 and 48 h. HUVEC were also pre-treated with simvastatin to examine its effect. RT-PCR was used to assess changes in the gene expression of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), Monocyte chemotactic protein-1 (MCP-1), E-selectin, and angiotensin receptor type 1 (AT1R). Protein abundance of the investigated molecules was assessed by immunoblotting. KEY FINDINGS: Treatment with 100 MUM IS for 16 h induced a 2-fold increase in the expression of ICAM-1, VCAM-1, and MCP-1. At a concentration of 1000 MUM, there was a 2-3-fold increase. An extended treatment period at low concentrations was associated with a 2-3 fold increase and the increase of ICAM-1 and VCAM-1 was more prominent under high concentration. Results of immunoblotting confirmed an increase in the abundance of ICAM-1, VCAM-1 and MCP-1. No significant change was noted in E-selectin and AT1R according to concentration or treatment duration. Pre-treatment with simvastatin did not alter IS-induced changes. SIGNIFICANCE: IS increased the expression of adhesion molecules of endothelial cells exhibiting a concentration and duration dependent pattern. Simvastatin did not demonstrate any effect on IS-associated endothelial activation. PMID- 22056375 TI - Activation of Notch1 signaling by marrow-derived mesenchymal stem cells through cell-cell contact inhibits proliferation of hepatic stellate cells. AB - AIMS: Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported in many studies to reduce liver fibrosis. Apart from the paracrine mechanism by which the antifibrotic effects of BMSCs inhibit activated hepatic stellate cells (HSCs), the effects of direct interplay and juxtacrine signaling between the two cell types are poorly understood. The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated HSCs. MAIN METHODS: We show here that BMSCs directly cocultured with HSCs significantly suppressed the proliferation and alpha-smooth muscle actin (alpha-SMA) expression of HSCs. Moreover, the Notch1 and Hes1 mRNA levels and the Hes1 protein level in cocultured HSCs were evidently higher than in other models. Blocking the Notch signaling pathway with Notch1 siRNA caused the increased expression of phospho Akt and greater cell growth of cocultured HSCs. This effect was attenuated by the PI3K inhibitor LY294002. KEY FINDINGS: In conclusion, our results demonstrated that BMSCs remarkably inhibited the proliferation of HSCs through a cell-cell contact mode that was partially mediated by Notch pathway activation. In addition, the PI3K/Akt pathway is involved in HSC growth inhibition by the Notch pathway. SIGNIFICANCE: These findings demonstrated that BMSCs directly modulate HSCs in vitro via Notch signaling cascades. Our results may provide new insights into the treatment of hepatic fibrosis with BMSCs. PMID- 22056376 TI - Vancomycin serum concentration during febrile neutropenia in patients with acute myeloid leukemia. AB - BACKGROUND: Adult leukemia patients with febrile neutropenia have a higher volume of distribution requiring increased drug doses. We performed a survey of vancomycin use in that population to assess the accuracy of our dosing guidelines. METHODS: We retrospectively reviewed the charts and laboratory results of vancomycin prescription and monitoring in adult acute myeloid leukemia patients with febrile neutropenia in a teaching hospital. RESULTS: Fifty-four patients received 67 vancomycin courses between January 2005 and April 2007. A loading dose was used in 97% of cases dosed at a mean 15.5+/-3.3mg/kg. It was followed by a continuous infusion of an average 35.4+/-6.9mg/kg per day maintenance dose. Serum monitoring yielded serum levels above the 20mg/L target in only 12% of cases. Despite higher dose, the target concentration was only reached in 32% of cases, after a mean 1.5 dose adjustment. The mean final maintenance dose was 42.1+/-9.4mg/kg per day. Vancomycin was well tolerated and induced only two temporary increases in serum creatinine. The treatment was microbiologically justified in only two cases. The mean length of therapy was 7.7+/-4.4 days and 41 over 65 (63%) non-documented infections were treated for more than five days despite local guidelines recommending a maximum 5-day course without bacterial documentation. Overall, only seven (10%) vancomycin courses complied with all defined criteria. CONCLUSIONS: Vancomycin use was not optimal. We updated our guidelines after the study to dramatically reduce vancomycin indications in leukemia patients. When it is indicated, following the loading dose, we more closely monitor vancomycin serum levels to allow for an earlier dose adjustment when necessary. PMID- 22056377 TI - Prevalence and characterization of extended spectrum beta-lactamases in Klebsiella-Enterobacter-Serratia group bacteria, in Algeria. AB - OBJECTIVES: The authors had for aim to assess the local epidemiology, antibiotic resistance, and molecular typing of expanded spectrum betalactamase producing Klebsiella, Enterobacter, and Serratia (ESBL KES). MATERIALS AND METHODS: Two hundred and seven strains of the KES group were isolated in the microbiology laboratory of the Annaba Ibn Rochd hospital in 2009. The antibiotic resistance (diffusion method and MIC) was tested and ESBL detection was performed as recommended by the Clinical Laboratory Standard Institute (CLSI). The characterization of genes for resistance to beta-lactams (CTX-M-1, TEM, and SHV) and AmpC cephalosporinase (DHA-1) was performed by polymerase chain reaction. The epidemiological relationship among identified strains was analyzed by Pulsed Field Gel Electrophoresis (PFGE). Genetic transfers were performed by conjugation using sodium azide resistant Escherichia coli K(12)J(5) as recipient strain. RESULTS: The overall incidence of ESBL KES was 31.4% (65/207) distributed as follows: 17.4% of Klebsiella spp., 7.2% Enterobacter spp., and 6.8% Serratia marcescens. The beta-lactamase CTX-M 1 types were predominant (88%), followed by TEM (36.5%), and SHV (31.1%). Twenty-three strains expressed at least two bla genes. DHA-1 type cephalosporinase was found in 4 E. cloacae associated with CTX M-1. Several epidemic clones were determined. Conjugation experiments showed that bla(CTX-M), bla(TEM), and bla(SHV) were carried by conjugative plasmids of high molecular weight (>=125kb). CONCLUSIONS: This study revealed a high frequency of ESBL KES with a predominance of CTX-M-1. This high rate of ESBLs could be due to a clonal spread and the emergence of new epidemic clones. PMID- 22056378 TI - [Update on the management of fungal infections]. PMID- 22056379 TI - T cell-driven initiation and propagation of autoimmune diabetes. AB - The destruction of beta cells in type 1 diabetes in humans and in autoimmune diabetes in the NOD mouse model is a consequence of chronic islet inflammation in the pancreas. The T cell-driven autoimmune response is initiated by environmental triggers which are influenced by the state of intestinal homeostasis and the microbiota. The disease process can be separated into two phases: firstly, initiation of mild, controlled, long-term infiltration and secondly, propagation of invasive inflammation which quickly progresses to beta cell deletion and autoimmune diabetes. In this review, we will discuss the cellular and molecular triggers that might be required for these two phases in the context of other issues including the unique anatomical location of pancreas, the location of T cell priming, the requirements for islet entry, and the events that ultimately drive beta cell destruction and the onset of diabetes. PMID- 22056380 TI - Single input optimal control for globally coupled neuron networks. AB - We consider the problem of desynchronizing a network of synchronized, globally (all-to-all) coupled neurons using an input to a single neuron. This is done by applying the discrete time dynamic programming method to reduced phase models for neural populations. This technique numerically minimizes a certain cost function over the whole state space, and is applied to a Kuramoto model and a reduced phase model for Hodgkin-Huxley neurons with electrotonic coupling. We evaluate the effectiveness of control inputs obtained by averaging over results obtained for different coupling strengths. We also investigate the applicability of this method to Hodgkin-Huxley models driven by multiplicative stimuli. PMID- 22056381 TI - IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors. AB - Solid tumors are complex masses with a local microenvironment, or stroma, that supports tumor growth and progression. Among the diverse tumor-supporting stromal cells is a heterogeneous population of myeloid-derived cells. These cells are alternatively activated and contribute to the immunosuppressive environment of the tumor; overcoming their immunosuppressive effects may improve the efficacy of cancer immunotherapies. We recently found that engineering tumor-specific CD8(+) T cells to secrete the inflammatory cytokine IL-12 improved their therapeutic efficacy in the B16 mouse model of established melanoma. Here, we report the mechanism underlying this finding. Surprisingly, direct binding of IL-12 to receptors on lymphocytes or NK cells was not required. Instead, IL-12 sensitized bone marrow-derived tumor stromal cells, including CD11b(+)F4/80(hi) macrophages, CD11b(+)MHCII(hi)CD11c(hi) dendritic cells, and CD11b(+)Gr-1(hi) myeloid-derived suppressor cells, causing them to enhance the effects of adoptively transferred CD8(+) T cells. This reprogramming of myeloid-derived cells occurred partly through IFN-gamma. Surprisingly, direct presentation of antigen to the transferred CD8(+) T cells by tumor was not necessary; however, MHCI expression on host cells was essential for IL-12-mediated antitumor enhancements. These results are consistent with a model in which IL-12 enhances the ability of CD8(+) T cells to collapse large vascularized tumors by triggering programmatic changes in otherwise suppressive antigen-presenting cells within tumors and support the use of IL-12 as part of immunotherapy for the treatment of solid tumors. PMID- 22056382 TI - Crosstalk between the canonical NF-kappaB and Notch signaling pathways inhibits Ppargamma expression and promotes pancreatic cancer progression in mice. AB - The majority of human pancreatic cancers have activating mutations in the KRAS proto-oncogene. These mutations result in increased activity of the NF-kappaB pathway and the subsequent constitutive production of proinflammatory cytokines. Here, we show that inhibitor of kappaB kinase 2 (Ikk2), a component of the canonical NF-kappaB signaling pathway, synergizes with basal Notch signaling to upregulate transcription of primary Notch target genes, resulting in suppression of antiinflammatory protein expression and promotion of pancreatic carcinogenesis in mice. We found that in the Kras(G12D)Pdx1-cre mouse model of pancreatic cancer, genetic deletion of Ikk2 in initiated pre-malignant epithelial cells substantially delayed pancreatic oncogenesis and resulted in downregulation of the classical Notch target genes Hes1 and Hey1. Tnf-alpha stimulated canonical NF kappaB signaling and, in collaboration with basal Notch signals, induced optimal expression of Notch targets. Mechanistically, Tnf-alpha stimulation resulted in phosphorylation of histone H3 at the Hes1 promoter, and this signal was lost with Ikk2 deletion. Hes1 suppresses expression of Pparg, which encodes the antiinflammatory nuclear receptor Ppargamma. Thus, crosstalk between Tnf alpha/Ikk2 and Notch sustains the intrinsic inflammatory profile of transformed cells. These findings reveal what we believe to be a novel interaction between oncogenic inflammation and a major cell fate pathway and show how these pathways can cooperate to promote cancer progression. PMID- 22056383 TI - Connexins protect mouse pancreatic beta cells against apoptosis. AB - Type 1 diabetes develops when most insulin-producing beta cells of the pancreas are killed by an autoimmune attack. The in vivo conditions modulating the sensitivity and resistance of beta cells to this attack remain largely obscure. Here, we show that connexin 36 (Cx36), a trans-membrane protein that forms gap junctions between beta cells in the pancreatic islets, protects mouse beta cells against both cytotoxic drugs and cytokines that prevail in the islet environment at the onset of type 1 diabetes. We documented that this protection was at least partially dependent on intercellular communication, which Cx36 and other types of connexin channels establish within pancreatic islets. We further found that proinflammatory cytokines decreased expression of Cx36 and that experimental reduction or augmentation of Cx36 levels increased or decreased beta cell apoptosis, respectively. Thus, we conclude that Cx36 is central to beta cell protection from toxic insults. PMID- 22056384 TI - Inflammation-induced subventricular zone dysfunction leads to olfactory deficits in a targeted mouse model of multiple sclerosis. AB - Neural stem cells (NSCs) persist in defined brain niches, including the subventricular zone (SVZ), throughout adulthood and generate new neurons destined to support specific neurological functions. Whether brain diseases such as multiple sclerosis (MS) are associated with changes in adult NSCs and whether this might contribute to the development and/or persistence of neurological deficits remains poorly investigated. We examined SVZ function in mice in which we targeted an MS-like pathology to the forebrain. In these mice, which we refer to herein as targeted EAE (tEAE) mice, there was a reduction in the number of neuroblasts compared with control mice. Altered expression of the transcription factors Olig2 and Dlx2 in the tEAE SVZ niche was associated with amplification of pro-oligodendrogenic transit-amplifying cells and decreased neuroblast generation, which resulted in persistent reduction in olfactory bulb neurogenesis. Altered SVZ neurogenesis led to impaired long-term olfactory memory, mimicking the olfactory dysfunction observed in MS patients. Importantly, we also found that neurogenesis was reduced in the SVZ of MS patients compared with controls. Thus, our findings suggest that neuroinflammation induces functional alteration of adult NSCs that may contribute to olfactory dysfunction in MS patients. PMID- 22056385 TI - Activation of K(ATP) channels suppresses glucose production in humans. AB - Increased endogenous glucose production (EGP) is a hallmark of type 2 diabetes mellitus. While there is evidence for central regulation of EGP by activation of hypothalamic ATP-sensitive potassium (K(ATP)) channels in rodents, whether these central pathways contribute to regulation of EGP in humans remains to be determined. Here we present evidence for central nervous system regulation of EGP in humans that is consistent with complementary rodent studies. Oral administration of the K(ATP) channel activator diazoxide under fixed hormonal conditions substantially decreased EGP in nondiabetic humans and Sprague Dawley rats. In rats, comparable doses of oral diazoxide attained appreciable concentrations in the cerebrospinal fluid, and the effects of oral diazoxide were abolished by i.c.v. administration of the K(ATP) channel blocker glibenclamide. These results suggest that activation of hypothalamic K(ATP) channels may be an important regulator of EGP in humans and that this pathway could be a target for treatment of hyperglycemia in type 2 diabetes mellitus. PMID- 22056386 TI - PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target. AB - Parathyroid hormone-related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer - it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention. PMID- 22056387 TI - Diode-less bilayer oxide (WO(x)-NbO(x)) device for cross-point resistive memory applications. AB - The combination of a threshold switching device and a resistive switching (RS) device was proposed to suppress the undesired sneak current for the integration of bipolar RS cells in a cross-point array type memory. A simulation for this hybrid-type device shows that the matching of key parameters between switch element and memory element is an important issue. Based on the threshold switching oxides, a conceptual structure with a simple metal-oxide 1-oxide 2 metal stack was provided to accommodate the evolution trend. We show that electroformed W-NbO(x)-Pt devices can simultaneously exhibit both threshold switching and memory switching. A qualitative model was suggested to elucidate the unique properties in a W-NbO(x)-Pt stack, where threshold switching is associated with a localized metal-insulator transition in the NbO(x) bulk, and the bipolar RS derives from a redox at the tip of the localized filament at the WO(x)-NbO(x) interface. Such a simple metal-oxide-metal structure, with functionally separated bulk and interface effects, provides a fabrication advantage for future high-density cross-point memory devices. PMID- 22056388 TI - Molecular cloning and characterization of a novel human papillomavirus, HPV 126, isolated from a flat wart-like lesion with intracytoplasmic inclusion bodies and a peculiar distribution of Ki-67 and p53. AB - Infection with certain human papillomavirus types induces warts with specific macroscopic and microscopic features. We observed multiple flat wart-like lesions on the chest, neck and extremities of an adult T-cell leukemia patient. Histologically, atypical intracytoplasmic inclusion bodies currently known to be pathognomonic for genus gamma or mu papillomaviruses were disclosed in some cells of the epidermis showing histological features compatible with flat warts. In the present study, a novel human papillomavirus was identified and its whole genome, 7326 bp in length, was cloned and characterized. Phylogenetic analysis showed the virus designated as HPV126 to be a novel type of genus gamma papillomavirus. Strikingly, Ki-67 and p53 expression was found to be increased in all layers of the epidermis except for horny layer, contrasting to expression restricted to the basal and lower spinous layers in ordinary flat warts. PMID- 22056389 TI - In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity. AB - Acquisition of alpha2-6 sialoside receptor specificity by alpha2-3 specific highly-pathogenic avian influenza viruses (H5N1) is thought to be a prerequisite for efficient transmission in humans. By in vitro selection for binding alpha2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (S227N, D187G, E190G, and Q196R) that revealed modestly increased alpha2-6 and minimally decreased alpha2-3 binding by glycan array analysis. However, a mutant virus combining Q196R with mutations from previous pandemic viruses (Q226L and G228S) revealed predominantly alpha2-6 binding. Unlike the wild type H5N1, this mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets. However, a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets. The complex changes required for airborne transmissibility in ferrets suggest that extensive evolution is needed for H5N1 transmissibility in humans. PMID- 22056390 TI - Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation. AB - Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells. PMID- 22056391 TI - Multiple versus single and other estimates of baseline proteinuria status as predictors of adverse outcomes in the general population. AB - BACKGROUND: The association of proteinuria and adverse clinical outcomes is well established. The optimal method of classifying proteinuria status for study participants in whom it is measured multiple times is unknown, especially when the frequency of measurement varies between participants. STUDY DESIGN: Population-based longitudinal study. SETTING & PARTICIPANTS: All adults with at least one outpatient serum creatinine measurement in the province of Alberta, Canada. FACTOR: Proteinuria (dipstick, albumin-creatinine ratio [ACR]). OUTCOMES: All-cause mortality, end-stage renal disease, or doubling of serum creatinine level. MEASURES: All outpatient urine dipstick and ACR measurements in the 6 month period before and after the first (index) estimated glomerular filtration rate were used to establish baseline proteinuria. Dipstick measures were analyzed as ceiling (median value up to the next integer), floor (median value down to the next integer), high (single highest dipstick value), low (single lowest dipstick value), and first (first available dipstick value only). Measurements of ACR were evaluated similarly and a median (median of all ACR measurements) value was added. RESULTS: Of 920,985 participants, 17% (n = 160,548) had multiple dipstick urinalysis measurements and 22% (n = 22,814) had multiple ACR measurements. With single measurements, absolute rates of mortality and renal outcomes were lower in every proteinuria category compared with multiple measurements. In contrast, the relative increase in rate ratio was greater with increasing proteinuria in patients with single measurements compared with those with multiple measurements. In all classification systems evaluated, more severe proteinuria was associated with significantly higher rates of both outcomes (all P for trend <0.001). LIMITATIONS: Lack of a gold standard for choosing between methods. CONCLUSIONS: Rates of adverse outcomes related to multiple baseline proteinuria/albuminuria measurements were similar, independent of the measure of baseline proteinuria that was used to combine results. In contrast, discarding follow-up measurements and relying on only the first measurement led to lower estimates of absolute and relative risk for each proteinuria category. PMID- 22056392 TI - Dialysis patients and critical illness. AB - Dialysis patients account for 1%-9% of all intensive care unit (ICU) admissions. As a result of the increasing prevalence of patients treated with long-term dialysis and the changing demographics of this population, the number of dialysis patients requiring hospitalization and ICU support is expected to increase. Critically ill dialysis patients have more comorbid conditions and higher severity of illness than the general population, resulting in higher ICU and in hospital mortality rates, but lower than for critically ill patients with acute kidney injury, suggesting that illness severity may contribute more to adverse outcomes than dialysis status. This review focuses on the epidemiology, prognosis, and short- and long-term outcomes of long-term dialysis patients admitted to the ICU, with data suggesting that dialysis patients have reasonable outcomes after ICU admission compared with the general population. It is important to recognize that illness severity and comorbid conditions rather than dialysis status account for much of the observed differences in short-term mortality rates. There are limited data to guide decision making regarding which dialysis patients may benefit from ICU admission, with common prognostic scoring systems routinely overestimating mortality in dialysis patients. PMID- 22056393 TI - Neuroontology, neurobiological naturalism, and consciousness: a challenge to scientific reduction and a solution. AB - One of the great challenges to a science of consciousness is the inability to reduce critical features of consciousness to neural processes. In this paper I identify four neuroontologically irreducible features (NOIF) - referral of neural states, mental unity, qualia, and mental causation - defined as aspects of consciousness in which subjective experience is not wholly reducible to objectively observed or objectively understood neurons (ontological subjectivity). I next analyze the emergent and unique system properties of the neural hierarchy and argue that while the NOIF are indeed ontologically subjective, each of the NOIF individually can be explained by the unique architecture and functional properties of the neural hierarchy that lead to both emergent properties and their irreducibility in a manner that does not violate any known physical laws nor require any new physics or the application of physics to emergence or reduction beyond that normally applied to biology in general. I conclude that consciousness is a neurobiologically unique and local phenomenon that is specific to particular neural systems, a view that is consistent with both ontological subjectivity and biological naturalism. I call this position weakly emergent nonreductive physicalism or neurobiological naturalism. PMID- 22056394 TI - Modeling evolution of speech. Comment on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22056395 TI - Embodied compositionality. Comment on "Modeling the cultural evolution of language" by Luc Steels. PMID- 22056396 TI - Is anti-TNF therapy safer than previously thought? PMID- 22056397 TI - Factors associated with treatment response to etanercept in juvenile idiopathic arthritis. AB - CONTEXT: Since the introduction of biologic therapies, the pharmacological treatment approach for juvenile idiopathic arthritis (JIA) has changed substantially, with achievement of inactive disease as a realistic goal. OBJECTIVE: To determine the response to therapy after initiation of etanercept therapy among patients with JIA and to examine the association between baseline factors and response to etanercept treatment. DESIGN, SETTING, AND PATIENTS: The Arthritis and Biologicals in Children Register, an ongoing prospective observational study since 1999, includes all Dutch JIA patients who used biologic agents. All biologically naive patients who started etanercept before October 2009 were included, with follow-up data to January 2011. Among the 262 patients, 185 (71%) were female, 46 (18%) had systemic-onset, and the median age at initiation of etanercept treatment was 12.4 years. MAIN OUTCOME MEASURES: Excellent response (inactive disease or discontinuation earlier due to disease remission), intermediate response (more than 50% improvement from baseline, but no inactive disease), and poor response (less than 50% improvement from baseline or discontinuation earlier due to ineffectiveness or intolerance) evaluated 15 months after initiation of etanercept. RESULTS: At 15 months after treatment initiation, 85 patients (32%) were considered excellent responders; 92 (36%), intermediate responders; and 85 (32%), poor responders. Compared with an intermediate or poor response, an excellent response was associated with lower baseline disability score (range, 0-3 points, with 0 being the best score; adjusted odds ratio [OR] per point increase, 0.49; 95% CI, 0.33-0.74); fewer disease-modifying antirheumatic drugs (DMARD) (including methotrexate) used before initiating etanercept (adjusted OR per DMARD used, 0.64; 95% CI, 0.43 0.95), and younger age at onset (adjusted OR per year increase, 0.92; 95% CI, 0.84-0.99). Compared with an intermediate or excellent response, a poor response was associated with systemic JIA (adjusted OR systemic vs nonsystemic categories, 2.92; 95% CI, 1.26-6.80), and female sex (adjusted OR female vs male, 2.16; 95% CI, 1.12-4.18). Within the first 15 months of etanercept treatment, 119 patients experienced 1 or more infectious, noninfectious, or serious adverse events, including 37 among those with an excellent response, 36 with an intermediate response, and 46 with a poor response. Within the first 15 months of treatment, 61 patients discontinued etanercept treatment, including 4 with an excellent response, 0 with an intermediate response, and 57 with a poor response. In a secondary analysis of 262 patients with a median follow-up of 35.6 months after initiation of etanercept, a range of 37% to 49% of patients reached inactive disease. The mean adherence to etanercept was 49.2 months (95% CI, 46.4-52.0) for patients with an excellent response after 15 months, 47.5 months (95% CI, 44.9 50.1) for patients with an intermediate response, and 17.4 months (95% CI, 13.6 21.2) for patients with a poor response. CONCLUSIONS: Among patients with JIA who initiated treatment with etanercept, one-third achieved an excellent response, one-third an intermediate response, and one-third a poor response to therapy. Achievement of an excellent response was associated with low baseline disability scores, DMARDs used before initiating etanercept, and younger age at onset of JIA. Achievement of a poor treatment response was associated with systemic JIA and female sex. PMID- 22056398 TI - Initiation of tumor necrosis factor-alpha antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. AB - CONTEXT: Although tumor necrosis factor (TNF)-alpha antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete. OBJECTIVES: To determine whether initiation of TNF-alpha antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization. DESIGN, SETTING, AND PATIENTS: Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-alpha antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate. MAIN OUTCOME MEASURE: Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-alpha antagonists or nonbiologic regimens. RESULTS: Study cohorts included 10,484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-alpha antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-alpha antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-alpha antagonists) and 9.60 (comparator) per 100 person years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-alpha antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections. CONCLUSION: Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-alpha antagonists was not associated with an increased risk of hospitalizations for serious infections. PMID- 22056399 TI - A novel type of prophenoloxidase from the kuruma prawn Marsupenaeus japonicus contributes to the melanization of plasma in crustaceans. AB - Melanization is one of the major immune responses in arthropods. Prophenoloxidases (proPOs) catalyze the oxidation of mono- or o-diphenols, a reaction that is the key initial step of melanin formation. Well-characterized proPOs from crustaceans are synthesized in haemocytes and are released into plasma in response to microbial attack. However, PO activity does exist in the plasma of haemolymph without pathogenic infections. Here, we demonstrate that a novel type of proPO contributes to such PO activity in the plasma fraction of haemolymph of crustaceans. The novel enzyme, which was purified from the plasma of the kuruma prawn (Marsupenaeus japonicus), possessed strong and specific monophenol and o-diphenol oxidation activity compared with that of known haemocyte-type proPO. Amino acid sequence analyses indicated that this enzyme was distinct from the known proPO. The cDNA sequence and deduced amino acid sequence of this enzyme has a putative binuclear copper center, and showed approximately 30% and 20% identity with the primary structures of reported proPO and haemocyanin sequences of the kuruma prawn, respectively. Reverse transcription PCR analysis showed that this enzyme was synthesized in the hepatopancreas rather than in haemocytes. Although the primary structure and enzymatic properties of this novel enzyme suggested that it is a phenoloxidase, its biogenesis, tissue distribution, and oligomeric state resemble those of haemocyanin, which belongs to the same protein family (type III copper protein). This novel proPO enzyme may share a role with the already characterized version, itself a major component of the innate immune system in crustaceans. PMID- 22056400 TI - Effects of exenatide in poorly controlled type 2 diabetes. AB - AIM: The aim of this retrospective analysis was to assess the clinical effectiveness of exenatide in patients with type 2 diabetes in routine clinical practice. METHODS: Patients with type 2 diabetes mellitus and inadequate glycemic control were commenced on exenatide in an out-patient setting. Effects on Hba1c, weight and BMI at 3- and 6-month intervals were recorded by a retrospective review of medical records. RESULTS: We examined a cross-section of 61 patients. The mean weight at treatment initiation was 114 kg and baseline Hba1c was 9.8% (84 mmol/mol). Mean reduction in Hba1c at 3 months was 0.8% (10 mmol/mol, P < 0.01) and mean reduction at 6 months was 0.5% (6 mmol/mol, P < 0.05). Mean weight loss at 3 months was 4.2 kg (P < 0.0001) and at 6 months was 6.6 kg (P < 0.0001). Seventeen patients were prescribed exenatide in addition to insulin, against current guidelines. This cohort of patients showed a greater mean reduction in weight (7.4 vs 6.2 kg) as compared to the group on exenatide without insulin, but mean Hba1c increased at 6 months by 0.35% (4 mmol/mol). CONCLUSION: Adjunctive exenatide treatment in patients with suboptimally controlled type 2 diabetes on oral hypoglycaemic medications, achieved reductions in Hba1c and weight, in line with published studies. However, in patients already on insulin, favourable results can be achieved by the addition of exenatide by careful patient selection and follow-up. PMID- 22056401 TI - Can we combine symptom scales for collaborative research projects? AB - Collaborative research projects have the potential to answer important research questions, which may otherwise require huge resources, funding, and time to complete. There are several scales for measuring psychotic symptoms in schizophrenia and other psychotic disorders, with the Scale for Assessment of Positive Symptoms (SAPS), Scale for Assessment of Negative Symptoms (SANS), Positive and Negative Symptom Scale (PANSS), and the Brief Psychiatric Rating Scale (BPRS) being among the most commonly used. High quality research efforts have used these three scales in different projects, and in order to merge study efforts, some means of combining data from these scales may be necessary. We reviewed correlations in published studies for these three scales, finding them to be highly correlated, however on comparison of the three scales there were considerable clinical differences between them. The paper discusses potential methods for combining the scales in collaborative research, including use of the recently developed standardised remission criteria for schizophrenia. PMID- 22056402 TI - Angiogenesis inhibition by the maleimide-based small molecule GNX-686. AB - We investigated the anti-angiogenic properties of GNX-686, a newly identified maleimide-based small molecule. In vitro studies on HUVEC showed that GNX-686 inhibited cell growth with an ED(50) of 20-25 MUM, while human HeLa tumor cells and non-transformed embryonic mouse fibroblasts were less sensitive for the drug. More importantly, at 4 MUM, a concentration that was non-toxic to any cell in culture, GNX-686 showed a significant inhibitory effect on tube formation by HUVEC, indicating a profound anti-angiogenic activity. Angiogenesis inhibition was subsequenly tested in the chorioallantoic membrane (CAM) of the chicken embryo. A significant angiostatic activity was observed in the CAM model, and results were compared with the effect of bevacizumab, a well known and clinically used VEGF inhibitor. Under our experimental conditions, GNX-686 was found to be as effective as bevacizumab, significantly changing the morphology of the vascular network, as illustrated and quantified by the relative number of branching points and the relative mean mesh size of the vascular network. In another in vivo model of neovascularization, the mouse retinopathy of prematurity (ROP), the vascular network of GNX-686-treated mice was significantly altered, reducing the density of the retinal microvasculature, as compared to the control retinas. Immunohistochemical processing of the GNX-686 treated (4MUM) eyes showed over 50% reduction of the number of cell nuclei associated with neovasculature, as compared to the control-treated eye. Taken together these results demonstrate that GNX-686 is a promising anti-angiogenic compound that could be developed for the treatment of diseases characterized by aberrant angiogenesis such as ocular pathologies and cancer. PMID- 22056403 TI - Comprehensive handbook for developing a bladder cancer cystectomy database. AB - OBJECTIVE: In an effort to standardize data collection for research regarding bladder cancer, the Bladder Cancer Working Group sought to provide a handbook that can be used as a guide for prospective or retrospective data collection. METHODS: Expert opinions for various data groups were compiled through a team of researchers at the BCAN. Peer review of each data group was performed from within the group. RESULTS: Essential and comprehensive data elements are provided for 9 groups of data elements, including demographics, comorbidities, staging, laboratory data, operative details, pathology, complications, outcomes, and quality of life measurements. CONCLUSIONS: Establishment of a comprehensive bladder cancer database is important in initiating multicenter collaborations. While not every data point is critical, this review may be useful in serving as a reference in initiating projects and providing a framework for collaborations. PMID- 22056404 TI - Gender-specific differences in cancer-specific survival after radical cystectomy for patients with urothelial carcinoma of the urinary bladder in pathologic tumor stage T4a. AB - BACKGROUND: Bladder cancer (UCB) staged pT4a show heterogeneous outcome after radical cystectomy (RC). No risk model has been established to date. Despite gender-specific differences, no comparative studies exist for this tumor stage. MATERIALS AND METHODS: Cancer-specific survival (CSS) of 245 UCB patients without neoadjuvant chemotherapy staged pT4a, pN0-2, M0 after RC were analyzed in a retrospective multi-center study. Seventeen patients were excluded from further analysis due to carcinoma in situ (CIS) of the prostatic urethra and/or positive surgical margins. Average follow-up period was 30 months (IQR: 14-45). The influence of different clinical and histopathologic variables on CSS was determined through uni- and multivariate Cox regression analyses. Two risk groups were generated using factors with independent effect in multivariate models. Internal validity of the prediction model was evaluated by bootstrapping. RESULTS: Eighty-four percent of the patients (n = 192) were male; 72% (n = 165) showed lymphovascular invasion (LVI). The 5-year CSS rate was 31%, and significantly different between male and female (35% vs. 15%, P = 0.003). Multivariate Cox regression modeling, female gender (HR = 1.83, P = 0.008), LVI (HR = 1.92, P = 0.005), and absence of adjuvant chemotherapy (HR = 0.61, P = 0.020) significantly worsened CSS. Two risk groups were generated using these 3 criteria, which differed significantly between each other in CSS (5-year-CSS: 46% vs. 12%, P < 0.001). The c-index value of the risk model was 0.61 (95% CI: 0.53 0.68, P < 0.001). CONCLUSIONS: Prognosis in UCB staged pT4a is heterogeneous. Female gender and LVI are adverse factors. Adjuvant chemotherapy seems to improve outcome. The present analysis establishes the first risk model for this demanding tumor stage. PMID- 22056405 TI - Mitochondrial DNA deletions and differential mitochondrial DNA content in Rhesus monkeys: implications for aging. AB - The purpose of this study was to determine the relationship between mitochondrial DNA (mtDNA) deletions, mtDNA content and aging in rhesus monkeys. Using 2 sets of specific primers, we amplified an 8 kb mtDNA fragment covering a common 5.7 kb deletion and the entire 16.5 kb mitochondrial genome in the brain and buffy-coats of young and aged monkeys. We studied a total of 66 DNA samples: 39 were prepared from a buffy-coat and 27 were prepared from occipital cortex tissues. The mtDNA data were assessed using a permutation test to identify differences in mtDNA, in the different monkey groups. Using real-time RT-PCR strategy, we also assessed both mtDNA and nuclear DNA levels for young, aged and male and female monkeys. We found a 5.7 kb mtDNA deletion in 81.8% (54 of 66) of the total tested samples. In the young group of buffy-coat DNA, we found 5.7 kb deletions in 7 of 17 (41%), and in the aged group, we found 5.7 kb deletions in 12 of 22 (54%), suggesting that the prevalence of mtDNA deletions is related to age. We found decreased mRNA levels of mtDNA in aged monkeys relative to young monkeys. The increases in mtDNA deletions and mtDNA levels in aged rhesus monkeys suggest that damaged DNA accumulates as rhesus monkeys age and these altered mtDNA changes may have physiological relevance to compensate decreased mitochondrial function. PMID- 22056406 TI - Clinical and physiological features of postinfectious chronic cough associated with H1N1 infection. AB - BACKGROUND: Post infectious chronic cough is a disabling illness. In 2009 an influenza pandemic occurred due to a novel strain of H1N1 influenza. Prolonged symptoms such as chronic cough remaining after the infection has cleared have not been examined. This study sought to investigate the prevalence, characteristics and mechanism of chronic cough following laboratory-confirmed H1N1 2009 influenza. METHODS: Out of 836 eligible patients who had been tested by PCR assay for H1N1, 136 responders participated. Nineteen underwent detailed clinical investigation of cough, and airway function using symptom questionnaires, hypertonic saline challenge, and cough monitoring. RESULTS: Post H1N1 chronic cough was reported by 43%, and chronic cough after non-H1N1 infection was present in 36% of participants. In the participants who progressed to testing objectively measured cough frequency was 3 times greater; there was a 9-fold increase in cough reflex sensitivity and greater quality of life impairment in the participants with postinfectious chronic cough following H1N1 infection than for the participants with no cough following H1N1 infection and for the healthy controls. CONCLUSIONS: This study reports the first evaluation of chronic cough following H1N1 infection. Patients that develop chronic cough after H1N1 infection display increased cough reflex sensitivity up to 220 days after confirmed infection. There is an absence of associated risk factors and less impairment in quality of life compared to those patients normally seen in a specialist cough clinic. The associated mechanism was found to be cough reflex hypersensitivity. TRIAL REGISTRATION: This clinical trial has been registered with the Australian New Zealand Clinical Trials Register, ACTRN12610000540011. PMID- 22056407 TI - Passive loss of hydrogen sulfide in biological experiments. AB - Hydrogen sulfide (H(2)S) is a volatile gas of considerable interest as a physiologically relevant signaling molecule, but this volatility has typically been overlooked in the context of biological experiments. We examined volatility of 10 and 100 MUM H(2)S (Na(2)S.9H(2)O) in real time with polarographic electrodes in three commonly employed experimental apparatuses: 24-well tissue culture plates (WP), muscle myograph baths (MB), and the Langendorff perfused heart apparatus (LPH). H(2)S loss from all apparatuses was rapid and exponential, with half-times (t(1/2)) of 5 min (WP), less than 4 min (MB), and less than 0.5 min (LPH). The t(1/2) for H(2)S loss from MB bubbled with 100% oxygen was slightly longer than that for MB bubbled with 100% nitrogen; both were significantly shorter than stirred but unbubbled MB (>9 min). Therefore, even without tissue, H(2)S rapidly disappears from buffer under a variety of experimental conditions, and this is due to volatilization, not oxidation. The inability to maintain H(2)S concentration, even briefly, questions the accuracy of dose-response studies and the relevance of long-term (>10 min) exposure to a single treatment of H(2)S. These results also help to explain the discrepancy between low H(2)S concentrations in blood and tissues versus high concentrations of exogenous H(2)S required to produce physiological responses. PMID- 22056408 TI - Kinetic characterization of inhibition of human thrombin with DNA aptamers by turbidimetric assay. AB - A sensitive turbidimetric method for detecting fibrin association was used to study the kinetics of fibrinogen hydrolysis with thrombin. The data were complemented by high-performance liquid chromatography (HPLC) measurements of the peptide products, fibrinopeptides released during hydrolysis. Atomic force microscopy (AFM) data showed that the fibril diameter is the main geometric parameter influencing the turbidity. The turbidimetric assay was validated using thrombin with the standard activity. To study thrombin inhibitors, a kinetic model that allows estimating the inhibition constants and the type of inhibition was proposed. The kinetic model was used to study the inhibitory activity of the two DNA aptamers 15-TBA (thrombin-binding aptamer) and 31-TBA, which bind to thrombin exosites. For the first time, 31-TBA was shown to possess the competitive inhibition type, whereas the shortened aptamer 15-TBA has the noncompetitive inhibition type. PMID- 22056409 TI - Enantioselective recognition of mandelic acid based on gamma-globulin modified glassy carbon electrode. AB - A new chiral biosensor has been fabricated by immobilizing gamma-globulin on gold nanoparticles modified glassy carbon electrodes, which could recognize and detect mandelic acid (MA) enantiomers. Differential pulse voltammetry, quartz crystal microbalance, ultraviolet-visible spectroscopy, and atomic force microscopy were used to characterize the enantioselectivity. The results exhibited that gamma globulin modified electrode could enantioselectively recognize MA enantiomers, and larger response signals were obtained from R-MA. The factors influencing the performance of the resulting biosensor were investigated. The enantiomeric composition of R- and S-MA enantiomer mixtures could be determined by measuring the current responses of the sample. The developed electrodes have the advantages of simple preparation, good stability, and rapid detection. PMID- 22056410 TI - Surface-enhanced Raman scattering detection of wild-type and mutant p53 proteins at very low concentration in human serum. AB - The development of ultrasensitive and rapid approaches to detect tumor markers at very low concentrations even in a physiological environment represents a challenge in nano-medicine. The p53 protein is at the center of the cellular network that protects organisms against the insurgence of tumors, most of which are related to alteration of p53 expression. Therefore p53 is regarded as a valuable prognostic marker whose detection at high sensitivity may considerably contribute to early diagnosis of cancers. In this work we have applied an analytical method based on surface enhanced Raman spectroscopy with high sensitivity and rapidity to improve traditional bioaffinity techniques. The Raman reporter bifunctional linker 4-aminothiophenol (4-ATP) first assembled onto 50 nm gold nanoparticles (Nps) has then been azotated to bind low concentration wild type and two mutated forms of p53 proteins. The Raman signal enhancement of the resulting p53-(4-ATP-Np) systems has been used to identify the p53 molecules captured on a recognition substrate constituted by the azurin (Az) protein monolayer. Az has shown a strong association for both wild-type and mutated p53 proteins, allowing us to selectively detect these proteins at concentrations as low as 500 fM, in a human serum environment. PMID- 22056411 TI - Genetic consequences of anagenetic speciation in Acer okamotoanum (Sapindaceae) on Ullung Island, Korea. AB - BACKGROUND AND AIM: Anagenesis (also known as phyletic speciation) is an important process of speciation in endemic species of oceanic islands. We investigated genetic variation in Acer okamotoanum, an anagenetically derived species endemic to Ullung Island, South Korea, to infer genetic consequences of anagenesis in comparison with other groups that have undergone cladogenesis (and adaptive radiation). METHODS: We examined genetic variation based on eight polymorphic microsatellite markers from 145 individuals of A. okamotoanum and 134 individuals of its putative progenitor A. mono. We employed standard population genetic analyses, clustering analyses, Bayesian clustering analyses in STRUCTURE and bottleneck analyses. KEY RESULTS: Based on both the Neighbor-Joining tree and Bayesian clustering analyses, clear genetic distinctions were found between the two species. Genetic diversity in terms of allelic richness and heterozygosity shows slightly lower levels in A. okamotoanum in comparison with A. mono. Bayesian clustering analyses showed a relatively high F-value in the cluster of A. okamotoanum, suggesting a strong episode of genetic drift during colonization and speciation. There was no clear evidence of a bottleneck based on allelic frequency distribution and excess of observed heterozygotes, but the M-ratio indicated a historical bottleneck in several populations of A. okamotoanum. No geographical genetic structure within the island was found, and the genetic variation among populations of A. okamotoanum was quite low. CONCLUSIONS: We hypothesized that genetic consequences of oceanic-endemic plants derived via anagenesis would be quite different from those derived via cladogenesis. Populations of A. okamotoanum form a cluster and are clearly differentiated from A. mono, which suggests a single origin for the anagenetically derived island endemic. No pattern of geographical differentiation of populations occurs in A. okamotoanum, which supports the concept of initial founder populations diverging through time by accumulation of mutations in a relatively uniform environment without further specific differentiation. PMID- 22056412 TI - Xenograft models for preclinical drug testing: implications for adrenocortical cancer. AB - Adrenocortical carcinoma (ACC) is a very rare but aggressive tumor, whose biological and cellular features and processes underlying the development, progression and metastatic evolution are still obscure. Despite many attempts to use general cytostatic and cytotoxic drugs, the only available drug therapy for advanced ACC is still represented by mitotane (MTT). However, the mechanism of action of this adrenolytic derivative of the pesticide DDT has still been poorly characterized. In this context, the development of more specific drugs for ACC treatment is based on the knowledge of the molecular pathways involved in the tumor growth. Xenograft models for the screening of such drugs at preclinical levels is mandatory. In the first part of this review, we will summarize the "pro" and "con" of the different xenograft models available for anticancer drug testing in different types of tumors in general and in the last part, we will focus on the preclinical evidence obtained so far with the use of such models applied to drug screening for anticancer effects in ACC. PMID- 22056413 TI - Maturation of the growth axis in marsupials occurs gradually during post-natal life and over an equivalent developmental stage relative to eutherian species. AB - The separation of a nutrition-responsive insulin-like growth factor (IGF) system and a growth hormone (GH) responsive IGF system to control pre- and post-natal growth of developing mammals may originate from the constraints imposed by intra uterine development. In eutherian species that deliver relatively precocial young, maturation of the GH regulatory system is coincident with the time of birth. We measured the hepatic expression of the four key growth axis genes GH receptor, IGF-1 and -2, and IGFBBP-3, and plasma protein concentrations of IGF-1 from late fetal life through to adult stages of a marsupial, the tammar wallaby. The data clearly show that maturation of GH-regulated growth in marsupials occurs gradually over the course of post-natal life at an equivalent developmental stage to that of precocial eutherian mammals. This suggests that the timing of GH regulated growth in marsupials is not related to parturition but instead to the relative developmental stage. PMID- 22056414 TI - BMP action in the pituitary: its possible role in modulating somatostatin sensitivity in pituitary tumor cells. AB - The existence of a functional bone morphogenetic protein (BMP) system in the pituitary has been recognized. Recent studies have provided evidence that BMPs elicit differential actions in the regulation of prolactin (PRL) and adrenocorticotropin (ACTH) release in lactotropinoma and corticotropinoma cells, respectively. BMPs play a key role in the modulation of somatostatin receptor (SSTR) sensitivity of lactosomatotrope cells in an autocrine/paracrine manner. In addition, SSTR action enhances BMP responsiveness in corticotrope cells. The functional link between BMP receptor signaling and SSTR actions may be crucial for individual tolerance to somatostatin analogs for controlling PRL and ACTH production. Adjustment of the endogenous SSTR sensitivity may be an effective strategy to inhibit the growth activity and hormonal productivity of intractable pituitary tumors. PMID- 22056415 TI - Do Hv1 proton channels regulate the ionic and redox homeostasis of phagosomes? AB - Recent work on animal models has revealed the important role played by the voltage-gated proton channel Hv1 during bacterial killing by innate immune cells. Studies from mice lacking Hv1 channels showed that Hv1 proton channels are required for high-level production of reactive oxygen species (ROS) by the NADPH oxidase of phagocytes (NOX2) in two ways. First, Hv1 channels maintain a physiological membrane potential during the respiratory burst of neutrophils by providing a compensating charge for the electrons transferred by NOX2 from NADPH to superoxide. Second, Hv1 channels maintain a physiological cytosolic pH by extruding the acid generated by the NOX2-dependent consumption of NADPH. The two mechanisms directly sustain the activity of the NOX2 enzyme and indirectly sustain other neutrophil functions by enhancing the driving force for the entry of calcium into cells, thereby boosting cellular calcium signals. The increased depolarization of Hv1-deficient neutrophils aborted calcium responses to chemoattractants and revealed adhesion and migration defects that were associated with an impaired depolymerization of the cortical actin cytoskeleton. Current research aims to transpose these findings to phagosomes, the phagocytic vacuoles where bacterial killing takes place. However, the mechanisms that control the phagosomal pH appear to vary greatly between phagocytes: phagosomes rapidly acidify in macrophages but remain neutral for several minutes in neutrophils following ingestion of solid particles, whereas in dendritic cells phagosomes alkalinize, a mechanism thought to promote antigen cross-presentation. In this review, we discuss how the knowledge gained on the role of Hv1 channels at the plasma membrane of neutrophils can be used to study the regulation of the phagosomal pH, ROS, membrane potential, and calcium fluxes in different phagocytic cells. PMID- 22056416 TI - Gene expression profiling in adrenocortical neoplasia. AB - Transcriptome studies of adrenocortical tumors have shown clear differences between adenomas and carcinomas and identified two subgroups of carcinomas with different prognoses. This review focuses on how transcriptomes have enriched our knowledge about genes previously identified by classical candidate gene approaches, uncovered novel genes relevant to adrenocortical tumor biology, helped to identify and understand specific pathway alterations, and advanced the overall translational relevance of this field of research. PMID- 22056417 TI - Association study of candidate gene polymorphisms and obesity in a young Mexican American population from South Texas. AB - BACKGROUND AND AIMS: Obesity is increasingly a health problem and a risk factor for diabetes in young Mexican-American populations. Genetic association studies in older, mostly non-Hispanic populations have reported that polymorphisms in the candidate genes HSD11B1, CRP, ADIPOQ, PPARG, ANKK1, ABCC8 and SERPINF1 are associated with obesity or diabetes. We analyzed the polymorphisms rs846910, rs1205, rs1501299, rs1801282, rs1800497, rs757110 and rs1136287 in these candidate genes, for association with obesity and metabolic traits in a young Mexican-American population from south Texas. METHODS: Genotyping of the seven common SNPs were performed by allelic discrimination assays in 448 unrelated Mexican Americans (median age = 16 years) from south Texas. chi(2) tests and regression analyses using additive models were used for genetic association analyses adjusting for covariates; p values were corrected for multiple testing by permutation analyses. RESULTS: rs1800497 (ANKK1) shows association with waist circumference (p = 0.009) and retains the association (p = 0.03) after permutation testing. Analysis of metabolic quantitative traits shows that rs846910 (HSD11B1) was associated with HOMA-IR (p = 0.04) and triglycerides (p = 0.03), and rs1205 (CRP) with HOMA-IR (p = 0.03) and fasting glucose levels (p = 0.007). However, the quantitative traits associations are not maintained after permutation analysis. None of the other SNPs in this study showed associations with obesity or metabolic traits in this young Mexican-American population. CONCLUSIONS: We report a potential association between rs1800497 (linked to changes in brain dopamine receptor levels) and central obesity in a young Mexican American population. PMID- 22056418 TI - The neural optimal control hierarchy for motor control. AB - Our empirical, neuroscientific understanding of biological motor systems has been rapidly growing in recent years. However, this understanding has not been systematically mapped to a quantitative characterization of motor control based in control theory. Here, we attempt to bridge this gap by describing the neural optimal control hierarchy (NOCH), which can serve as a foundation for biologically plausible models of neural motor control. The NOCH has been constructed by taking recent control theoretic models of motor control, analyzing the required processes, generating neurally plausible equivalent calculations and mapping them on to the neural structures that have been empirically identified to form the anatomical basis of motor control. We demonstrate the utility of the NOCH by constructing a simple model based on the identified principles and testing it in two ways. First, we perturb specific anatomical elements of the model and compare the resulting motor behavior with clinical data in which the corresponding area of the brain has been damaged. We show that damaging the assigned functions of the basal ganglia and cerebellum can cause the movement deficiencies seen in patients with Huntington's disease and cerebellar lesions. Second, we demonstrate that single spiking neuron data from our model's motor cortical areas explain major features of single-cell responses recorded from the same primate areas. We suggest that together these results show how NOCH-based models can be used to unify a broad range of data relevant to biological motor control in a quantitative, control theoretic framework. PMID- 22056419 TI - DL-3-n-butylphthalide extends survival by attenuating glial activation in a mouse model of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease characterized by progressive muscular atrophy, paralysis and bulbar symptoms. Transgenic mice over-expressing human mutant Cu/Zn superoxide dismutase-1 (SOD1) mimicked the pathological phenotype of ALS. dl-3-n-butylphthalide (dl-NBP) has been demonstrated to play a neuroprotective role in cerebral ischemia, vascular dementia, and Alzheimer's disease. In the current study, we examined the effect of dl-NBP in Tg (SOD1-G93A) transgenic mice, a well-studied model of ALS. Following the symptomatic onset of disease, oral administration of dl-NBP significantly improved motor performance, extended the survival interval, attenuated motor neuron loss, and delayed motor unit reduction compared to vehicle controls. These observations were further corroborated by the significant reduction in immunoreactivity of CD11b and glial fibrillary acidic protein (GFAP), markers for microglia and astrocytes, respectively. Additionally, downregulation of nuclear factor kappaB (NF-kappaB) p65 and tumor necrosis factor alpha (TNF-alpha) protein levels and a slight upregulation of NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were found in the spinal cord of Tg (SOD1-G93A) mice treated by dl-NBP. These results suggest that dl-NBP might be a promising compound in the treatment of ALS. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22056420 TI - Acceptor and surface states of ZnO nanocrystals: a unified model. AB - Semiconductor nanocrystals have the potential for a range of applications in optoelectronics and nonlinear optics. As the surface-to-volume ratio increases, surface emission processes become more important. Using infrared (IR) and photoluminescence (PL) spectroscopy, we have developed a unified model for the acceptor and intragap surface states of ZnO nanocrystals. A PL peak was observed at 2.97 eV, in agreement with an acceptor level previously observed in the IR (Teklemichael et al 2011 Appl. Phys. Lett. 98 232112). The temperature dependence of the IR absorption peaks, which correspond to a hole binding energy of 0.46 eV, showed an ionization activation energy of only 0.08 eV. This activation energy is attributed to thermal excitation of the hole to surface states 0.38 eV above the valence band maximum. Therefore, while the acceptor is deep with respect to the bulk valence band, it is shallow with respect to surface states. A strong red PL emission centered at 1.84 eV, with an excitation onset of 3.0 eV, is attributed to surface recombination. PMID- 22056421 TI - [Assessment of a residency training program in endocrinology and nutrition by physicians: results of a survey]. AB - BACKGROUND AND OBJECTIVE: The current training program for resident physicians in endocrinology and nutrition (EN) organizes their medical learning. Program evaluation by physicians was assessed using a survey. MATERIAL AND METHOD: The survey asked about demographic variables, EN training methods, working time and center, and opinion on training program contents. RESULTS: Fifty-one members of Sociedad Castellano-Manchega de Endocrinologia, Nutricion y Diabetes, and Sociedad Andaluza de Endocrinologia y Nutricion completed the survey. Forty percent of them disagreed with the compulsory nature of internal medicine, cardiology, nephrology and, especially, neurology rotations (60%); a majority (>50%) were against several recommended rotations included in the program. The fourth year of residence was considered by 37.8% of respondents as the optimum time for outpatient and inpatient control and monitoring without direct supervision. The recommended monthly number of on-call duties was 3.8+/-1.2. We detected a positive opinion about extension of residence duration to 4.4+/-0.5 years. Doctoral thesis development during the residence period was not considered convenient by 66.7% of physicians. Finally, 97.8% of resident physicians would recommend residency in EN to other colleagues. CONCLUSIONS: Endocrinologists surveyed disagreed with different training program aspects such as the rotation system, skill acquisition timing, and on-call duties. Therefore, an adaptation of the current training program in EN would be required. PMID- 22056422 TI - The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: an observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes. AB - AIMS: To elucidate methodological questions in assessing the relationship between insulin treatment and cancer, since the risk of tumour growth generally increases with longer exposure time and higher dose of a growth promoting substance. METHODS: Continuous hazard functions for risk of breast and prostate cancer were estimated in relation to exposure of insulin glargine among diabetic patients included in the record system, Diab-Base, as well as in the general population in Sweden. RESULTS: In 7942 female diabetic patients, mean follow-up 7.0 years, 2014 patients initiated insulin glargine with a mean follow-up of 3.5 years. Among 11,613 men, mean follow-up 6.9 years, 2760 had a mean follow-up with glargine of 3.4 years. Risk of prostate cancer decreased significantly with longer exposure to insulin glargine (p=0.032), although average risk versus non-glargine was non significantly higher (HR 1.37, 95% CI 0.78-2.39). The breast cancer risk did not change with longer exposure to insulin glargine (p=0.35) and the mean risk was similar for glargine and non-glargine (p=0.12). With higher dose of insulin glargine, there was an increase in risk of prostate (p=0.037) and breast cancer (p=0.019). In diabetics, the mean risk of prostate cancer was decreased (HR 0.68, 95% CI 0.59-0.79) but similar for breast cancer (HR 0.95, 95% CI 0.78-1.14) compared to the general population and did not change with longer diabetes duration (p=0.68 and p=0.53 respectively). CONCLUSIONS: Analysing continuous hazard functions for cancer risk in relation to exposure time to an antidiabetic agent is an important complementary tool in diabetes and cancer research. PMID- 22056423 TI - Influence of thickeners on the fragmentation of fish meat sausage by mastication. AB - The influence of food thickeners (potato starch, guar gum, and xanthan gum and deionized water) on the breakdown of solid food was numerically analyzed, and an investigation was made into the cumulative size distribution of food fragments, textural properties, sensory evaluation and maximum transit velocity of a bolus in the pharynx.The results suggest that evaluating the breakability into small pieces was easily influenced by the addition ratio of the dispersion medium. However, in respect of the destruction process for the solid body, each sample was more strongly affected by the type of the dispersion medium than by the addition ratio of this medium.The destruction process was strongly influenced by the history of the breakdown caused by mastication when a liquid dispersion medium was added to the solid. However, when a high-viscosity sol was added to the solid, the destruction process was random and not affected by any history. PMID- 22056424 TI - Purification and characterization of a novel (S)-enantioselective transaminase from Pseudomonas fluorescens KNK08-18 for the synthesis of optically active amines. AB - Pseudomonas fluorescens KNK08-18, showing (S)-selective transaminase activity, was isolated from soil by an enrichment culture method using (S)-7-methoxy-2 aminotetraline as the main nitrogen source. A transaminase was purified from the strain to homogeneity in seven steps. The relative mass of the enzyme was estimated to be 53 kDa on SDS-polyacrylamide gel electrophoresis and 120 kDa by gel filtration, suggesting a homodimeric structure. The optimal pH and temperature for enzyme activity were about 8.0-8.5 and 40 degrees C. The purified enzyme produced (S)-7-methoxy-2-aminotetraline, (S)-SMA, from 7-methoxy 2-tetralone (SMT) with high enantioselectivity. Although (S)-1-phenylethylamine was the best amino donor, beta-alanine and 4-aminobutyric acid, which are good substrates for typical omega-amino acid transaminase (EC 2.6.1.18) and GABA transaminase (2.6.1.19), were not reacted. It aminated a broad range of carbonyl compounds containing aromatic, non-aromatic, and acidic and non-acidic substrates. PMID- 22056425 TI - Gene cloning and characterization of alpha-amino acid ester acyl transferase in Empedobacter brevis ATCC14234 and Sphingobacterium siyangensis AJ2458. AB - The gene encoding alpha-amino acid ester acyl transferase (AET), the enzyme that catalyzes the peptide-forming reaction from amino acid methyl esters and amino acids, was cloned from Empedobacter brevis ATCC14234 and Sphingobacterium siyangensis AJ2458 and expressed in Escherichia coli. This is the first report on the aet gene. It encodes a polypeptide composed of 616 (ATCC14234) and 619 (AJ2458) amino acids residues. The V(max) values of these recombinant enzymes during the catalysis of L-alanyl-L-glutamine formation from L-alanine methylester and L-glutamine were 1,010 U/mg (ATCC14234) and 1,154 U/mg (AJ2458). An amino acid sequence similarity search revealed 35% (ATCC14234) and 36% (AJ2458) identity with an alpha-amino acid ester hydrolase from Acetobacter pasteurianus, which contains an active-site serine in the consensus serine enzyme motif, GxSYxG. In the deduced amino acid sequences of AET from both bacteria, the GxSYxG motif was conserved, suggesting that AET is a serine enzyme. PMID- 22056426 TI - Mechanism of regulation of PPARG expression of mesenchymal stem cells by osteogenesis-mimicking extracellular matrices. AB - The mechanism of regulation of PPARG expression during the osteogenesis of human mesenchymal stem cells (MSCs) was investigated on an extracellular matrix (ECM) model that mimicked the stepwise osteogenesis ECM. Three matrices that mimicked the ECM of MSCs (stem cell matrices), the early stage ECM (early stage matrices), and the late stage ECM (late stage matrices) of osteogenesis were prepared and compared. The matrices showed different effects on the Wnt/beta-catenin signal. The beta-catenin signal was activated by endogenous Wnt through interaction with chondroitin sulfate chains to suppress PPARG expression on the stem cell matrices and early stage matrices but not on late stage matrices. PMID- 22056427 TI - Visualization of gluten and starch distributions in dough by fluorescence fingerprint imaging. AB - A novel method combining imaging techniques and fluorescence fingerprint (FF) data measurement was developed to visualize the distributions of gluten and starch in dough without any preprocessing. Fluorescence images of thin sections of gluten, starch, and dough were acquired under 63 different combinations of excitation and emission wavelengths, resulting in a set of data consisting of the FF data for each pixel. Cosine similarity values between the FF of each pixel in the dough and those of gluten and starch were calculated. Each pixel was colored according to the cosine similarity value to obtain a pseudo-color image showing the distributions of gluten and starch. The dough sample was then fluorescently stained for gluten and starch. The stained image showed patterns similar to the pseudo-color FF image, validating the effectiveness of the FF imaging method. The method proved to be a powerful visualization tool, applicable in fields other than food technology. PMID- 22056428 TI - Artemisia afra Jacq. ameliorates oxidative stress in the pancreas of streptozotocin-induced diabetic Wistar rats. AB - Diabetes is characterized by hyperglycemia resulting from defects in pancreatic insulin secretion and/or impaired target cell responsiveness to insulin, and Artemisia afra Jacq. is widely used in South Africa to treat the disease, but the mechanism of action is yet to be elucidated. This study explored the effect of oral administration of aqueous leaf extract of A. afra on the pancreas of streptozotocin-induced diabetic rats. We found that the extract significantly reduced blood glucose levels, accompanied by an increase in the serum insulin concentration. Moreover, the antioxidant enzymic activities of glutathione peroxidase, glutathione reductase, and superoxide dismutase also improved significantly after treatment with the extract. Increased pancreatic lipid peroxidation in the diabetic rats was also normalized by the extract. This study indicates that A. afra possesses hypoglycemic and antioxidant activities. Our findings suggest that the herb might exert its anti-diabetic activity by regenerating pancreatic beta cells, thereby stimulating the release of insulin. PMID- 22056429 TI - In vitro protein import of a putative amino acid transporter from Arabidopsis thaliana into chloroplasts and its suborganellar localization. AB - We identified a gene product of At5g19500 (At5g19500p) from Arabidopsis thaliana that is homologous to EcTyrP, a tyrosine-specific transporter from Escherichia coli. Computational analyses of the amino acid sequence of At5g19500p predicted 11 transmembrane domains (TMDs) and a potential plastid targeting signal at its amino terminus. As a first step toward understanding the possible role of At5g19500p in plant cells, we attempted to determine the localization of At5g19500p by an in vitro chloroplastic import assay using At5g19500p translated in a cell-free wheat germ system (Madin et al., Proc. Natl. Acad. Sci. USA, 97, 559-564 (2000)), followed by subfractionation of the chloroplasts. At5g19500p was successfully imported into chloroplasts, and the newly transported mature form of At5g19500p was recovered from the inner envelope membrane. PMID- 22056430 TI - Effects of polyethylene glycol on bovine intestine alkaline phosphatase activity and stability. AB - In this study, we evaluated the effects of polyethylene glycol (PEG) on bovine intestine alkaline phosphatase (BIALP) activity and stability. In the hydrolysis of p-nitrophenylphosphate (pNPP) at pH 9.8 at 20 degrees C, the k(cat)/K(m) values of BIALP plus 5-15% w/v free PEG with molecular masses of 1, 2, 6, and 20 kDa (PEG1000, PEG2000, PEG6000, and PEG20000 respectively) were 120-140%, 180 300%, 130-170%, and 110-140% respectively of that of BIALP without free PEG (1.8 uM(-1) s(-1)), indicating that activation by PEG2000 was the highest. Unmodified BIALP plus 5% PEG2000 and BIALP pegylated with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine exhibited 1.3-fold higher activity on average than that of BIALP without free PEG under various conditions, including pH 7.0-10.0 and 20-65 degrees C. The temperatures reducing initial activity by 50% in 30-min incubation of unmodified BIALP plus 5% PEG2000 and pegylated BIALP were 51 and 47 degrees C respectively, similar to that of BIALP without free PEG (49 degrees C). These results indicate that the addition of PEG2000 and pegylation increase BIALP activity without affecting its stability, suggesting that they can be used in enzyme immunoassay with BIALP to increase sensitivity and rapidity. PMID- 22056431 TI - Biochemical characterization of a thermophilic cellobiose 2-epimerase from a thermohalophilic bacterium, Rhodothermus marinus JCM9785. AB - Cellobiose 2-epimerase (CE) reversibly converts glucose residue to mannose residue at the reducing end of beta-1,4-linked oligosaccharides. It efficiently produces epilactose carrying prebiotic properties from lactose, but the utilization of known CEs is limited due to thermolability. We focused on thermoholophilic Rhodothermus marinus JCM9785 as a CE producer, since a CE-like gene was found in the genome of R. marinus DSM4252. CE activity was detected in the cell extract of R. marinus JCM9785. The deduced amino acid sequence of the CE gene from R. marinus JCM9785 (RmCE) was 94.2% identical to that from R. marinus DSM4252. The N-terminal amino acid sequence and tryptic peptide masses of the native enzyme matched those of RmCE. The recombinant RmCE was most active at 80 degrees C at pH 6.3, and stable in a range of pH 3.2-10.8 and below 80 degrees C. In contrast to other CEs, RmCE demonstrated higher preference for lactose over cellobiose. PMID- 22056432 TI - Characterization and functional modification of StaC and RebC, which are involved in the pyrrole oxidation of indolocarbazole biosynthesis. AB - The diversity of indolocarbazole natural products results from the differences in oxidation states of the pyrroline ring moiety. In the biosynthetic pathways for staurosporine and rebeccamycin, two homologous enzymes having 64% identity, StaC and RebC, are responsible for the selective production of K252c, which has one oxo group at the pyrroline ring, and arcyriaflavin A, which has two. Although StaC has a FAD-binding motif, most StaC molecules do not contain FAD, and the protein cannot be reconstituted with FAD in vitro. In this study, we mutated Ala 118 in StaC by replacing a glutamine that is conserved in FAD monooxygenases, resulting in increased FAD content as well as catalytic activity. In addition, mutations around the substrate-binding sites of StaC and RebC can change the product selectivity. Specifically, StaC-N244R-V246T and RebC-F216V-R239N mutants produced substantial amounts of arcyriaflavin A and K252c, respectively. PMID- 22056433 TI - Isolation of a novel carotenoid, OH-chlorobactene glucoside hexadecanoate, and related rare carotenoids from Rhodococcus sp. CIP and their antioxidative activities. AB - In the course of screening for antioxidative carotenoids from bacteria, we isolated and identified a novel carotenoid, OH-chlorobactene glucoside hexadecanoate (4), and rare carotenoids, OH-chlorobactene glucoside (1), OH-gamma carotene glucoside (2) and OH-4-keto-gamma-carotene glucoside hexadecanoate (3) from Rhodococcus sp. CIP. The singlet oxygen ((1)O(2)) quenching model of these carotenoids showed potent antioxidative activities IC(50) 14.6 uM for OH chlorobactene glucoside hexadecanoate (4), 6.5 uM for OH-chlorobactene glucoside (1), 9.9 uM for OH-gamma-carotene glucoside (2) and 7.3 uM for OH-4-keto-gamma carotene glucoside hexadecanoate (3). PMID- 22056434 TI - Identification of Acvr2a as a Th17 cell-specific gene induced during Th17 differentiation. AB - IL-17-producing T lymphocytes have been found to comprise a distinct lineage of T helper cells (Th17 cells) that are major causes of autoimmune diseases such as EAE, RA, and IBD. In this study, we found that activin receptor type-2A (Acvr2a) is a gene induced during the differentiation of this effector cell lineage as compared with naive T cells. The transcript of Acvr2a was not induced in Th1 and Th2 cells, and both TGF-beta and IL-6 were required for the induction of Acvr2a. When the differentiation of Th17 cells was inhibited by all tarans retinoic acid (ATRA) which induces regulatory T cell (Treg) differentiation under Th17 differentiation conditions, expression of Acvr2a was also inhibited. Hence we propose that Acvr2a is a Th17 specific gene making Th17 cells distinct from other helper T cells, Th1, Th2, and Treg. PMID- 22056435 TI - Characterization of shade avoidance responses in Lotus japonicus. AB - Sessile plants must continuously adjust their growth and development to optimize photosynthetic activity under ever-fluctuating light conditions. Among such light responses in plants, one of the best-characterized events is the so-called shade avoidance, for which a low ratio of the red (R):far-red (FR) light intensities is the most prominent stimulus. Such shade avoidance responses enable plants to overtop their neighbors, thereby enhancing fitness and competitiveness in their natural habitat. Considerable progress has been achieved during the last decade in understanding the molecular mechanisms underlying the shade avoidance responses in the model rosette plant, Arabidopsis thaliana. We characterize here the fundamental aspects of the shade avoidance responses in the model legume, Lotus japonicus, based on the fact that its phyllotaxis (or morphological architecture) is quite different from that of A. thaliana. It was found that L. japonicus displays the characteristic shade avoidance syndrome (SAS) under defined laboratory conditions (a low R:FR ratio, low light intensity, and low blue light intensity) that mimic the natural canopy. In particular, the outgrowth of axillary buds (i.e., both aerial and cotyledonary shoot branching) was severely inhibited in L. japonicus grown in the shade. These results are discussed with special emphasis on the unique aspects of SAS observed with this legume. PMID- 22056436 TI - Nerve and behavioral responses of mice to various umami substances. AB - Food contains various taste substances. Among them, umami substances play an important role with regard to the perception of the taste of food, but, few studies have examined the taste characteristics of representative umami substances other than monosodium L-glutamate (MSG). By conducting mouse behavioral studies (the 48-h 2-bottle preference test and the conditioned taste aversion test) and assessing gustatory nerve responses, we investigated the taste characteristics of unique umami substances, including sodium succinate, L theanine, betaine, and the enantiomer of MSG, D-MSG. Furthermore, we examined the synergy of umami with inosine 5'-monophoshate (IMP). In the case of the mice, sodium succinate had an umami taste and showed strong synergy with IMP. L theanine showed synergy with IMP but did not have an umami taste without IMP. In contrast, betaine did not have an umami taste or synergy with IMP. D-MSG might have weak synergy with IMP. PMID- 22056437 TI - Optimized method for determining free L-cysteine in rat plasma by high performance liquid chromatography with the 4-aminosulfonyl-7-fluoro-2,1,3 benzoxadiazole conversion reagent. AB - The analytical method was optimized for L-cysteine (Cys) in rat plasma with co existing L-cystine (Cyss). We observed that more than 100% Cyss in rat plasma was converted to Cys under typical conditions for the conversion with 7-fluoro-2,1,3 benzoxadiazole-4-sulfonate (SBD-F). Another conversion reagent, 4-aminosulfonyl-7 fluoro-2,1,3-benzoxadiazole (ABD-F), was then employed, with which the reaction could be carried out at a low temperature without the use of a reducing reagent. Under the optimized conditions of 4 degrees C and pH 8.3, the conversion ratio of Cyss to Cys in rat plasma was as low as 5-7%. We determined the Cys concentration in plasma of the portal vein of rats that had been orally administered with Cys and Cyss by applying this method. The result indicated that Cys administration and also Cyss administration effectively increased the plasma Cys level. The method developed in this study is well suited for determining the thiol compounds in biological samples. PMID- 22056438 TI - Polyphenolic compounds in clove and pimento and their antioxidative activities. AB - Two new polyphenolic glucosides, 6'-O-acetylisobiflorin (1) and (2S)-3-(4-hydroxy 3-methoxyphenyl)-propane-1,2-diol 1-O-(6'-O-galloyl)-beta-D-glucoside (2), were respectively isolated from the flower buds of Syzygium aromaticum and berries of Pimenta dioica. Each structure was elucidated on the basis of spectral analyses (NMR, MS and [alpha](D)) and chemical conversion. A total of twenty-seven known compounds from the plants were also characterized. The antioxidative activity of their extracts and the twenty-nine isolates including gallo- and ellagitannins was estimated by oxygen radical absorbance capacity (ORAC) assay, and eugenol (3), which was the most abundant ingredient in each plant extract, showed the most potent antioxidative activity [ORAC value of 39,270 umol TE (trolox equivalent)/g]. PMID- 22056439 TI - Cloning and overexpression of an NADH-dependent alcohol dehydrogenase gene from Candida maris involved in (R)-selective reduction of 5-acetylfuro[2,3-c]pyridine. AB - 5-((R)-1-Hydroxyethyl)-furo[2,3-c]pyridine ((R)-FPH) is a useful chiral building block in the synthesis of pharmaceuticals. An NADH-dependent alcohol dehydrogenase (AFPDH) isolated from Candida maris catalyzed the reduction of 5 acetylfuro[2,3-c]pyridine (AFP) to (R)-FPH with 100% enantiomeric excess. The gene encoding AFPDH was cloned and sequenced. The AFPDH gene comprises 762 bp and encodes a polypeptide of 27,230 Da. The deduced amino acid sequence showed a high degree of similarity to those of other members of the short-chain alcohol dehydrogenase superfamily. The AFPDH gene was overexpressed in Escherichia coli under the control of the lac promoter. One L of the cultured broth of an E. coli transformant coexpressing AFPDH and the glucose dehydrogenase (GDH) gene reduced 250 g of AFP to (R)-FPH in an organic solvent two-phase system. Under coupling with NADH regeneration using 2-propanol, 1 L of the cultured broth of an E. coli transformant expressing the AFPDH gene reduced 150 g of AFP to (R)-FPH. The optical purity of the (R)-FPH formed was 100% enantiomeric excess under both reaction conditions. PMID- 22056440 TI - Antioxidative activity and chemical constituents of edible terrestrial alga Nostoc commune Vauch. AB - The extract of terrestrial alga Nostoc commune Vauch. has high antioxidative activity. Our study on N. commune Vauch. resulted in the isolation of two beta ionone derivatives, nostocionone and 3-oxo-beta-ionone, together with four indole alkaloids, scytonemin, reduced scytonemin, N-(p-coumaroyl)tryptamine, and N acetyltryptamine. The structures of the isolated compounds were determined on the basis of 1D and 2D NMR and MS analyses. Among these isolates, nostocionone and reduced scytonemin demonstrated strong antioxidative activities which were assessed by using a beta-carotene oxidation assay. PMID- 22056441 TI - Ameliorating effects of short-chain inulin-like fructans on the healing stage of trinitrobenzene sulfonic acid-induced colitis in rats. AB - We evaluated the ameliorating effects of short-chain inulin-like fructans (SIF) with different degrees of polymerization (DP) on the healing stage of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. The rats were assigned to 3 groups 10 d after the colitis induction, and fed for 24 d on a control diet or diet including 60 g of DP4 or DP8/kg. The fecal myeloperoxidase (MPO) activity and IgA concentration were monitored every 7 d. The colonic MPO activities and cecal concentrations of organic acids, lactobacilli, bifidobacteria, mucin and IgA were measured at the end of the study. DP4, but not DP8, significantly reduced the colonic inflammation accompanied by higher cecal concentrations of short-chain fatty acids, propionate in particular, and lactic acid-producing bacteria. DP4 therefore accelerated the healing process of TNBS induced colitis, even when the treatment was initiated after inducing colitis. PMID- 22056442 TI - Biomimetic cyclization of epoxide precursors of indole mono-, sesqui- and diterpene alkaloids by Lewis acids. AB - Cyclization of the synthesized epoxide precursors of indole mono-, sesqui- and diterpene alkaloids was performed to elucidate the mechanism for biomimetic cationic cyclization to polycyclic structures. 3-(6,7-Epoxygeranyl)indole (11), 3 (10,11-epoxyfarnesyl)indole (2) and 3-(14,15-epoxygeranylgeranyl)indole (3) were respectively synthesized from geraniol, farnesol and geranylgeraniol in 6 or 7 steps. Four Lewis acids (MeAlCl(2), BF(3).OEt(2), TiCl(4) and SnCl(4)) were applied for biomimetic cyclization of the synthesized epoxide precursors. The cyclization products (one product from 11, four products from 2, and three products from 3) were isolated after separation by chromatography. Their structures were determined by using NMR (COSY, HSQC, HMBC, NOESY, etc.) and HRMS analyses. The results show that biomimetic cyclization gave new polycyclic compounds similar to natural indole terpene alkaloids. We conclude that the stability of cation intermediates should determine the preference for product formation by biomimetic cyclization when using a Lewis acid. PMID- 22056443 TI - Kjellmaniella crassifolia Miyabe (Gagome) extract modulates intestinal and systemic immune responses. AB - Kjellmaniella crassifolia Miyabe (gagome) is a brown alga. Oral gagome administration (oral gagome) resulted in significant upregulation of IL-10 and IFNgamma production by Peyer's patch cells. To assess the adjuvant activity of oral gagome, treated mice were subcutaneously injected with ovalbumin (OVA). The production of cytokines from antigen (Ag)-specific T cells in draining lymph nodes (dLN) and their proliferative response were significantly increased as compared with the control group. These enhancements were associated with increased CD44(hi)CD62L(-) activated/memory T cells in dLN as well as upregulation of Ag-specific IgA level in luminal contents. No upregulation of cytokine production by dLN T cells was observed in dectin-1-deficient mice, suggesting that the effect of gagome on cytokine production is largely dependent on the dectin-1 pathway despite its composite constituents. Our findings indicate that gagome is an effective immunomodulator and a potent adjuvant for both the intestinal and the systemic immune response. PMID- 22056444 TI - A systematic strategy for proteomic analysis of chloroplast protein complexes in wheat. AB - A systematic strategy was developed for the proteomic analysis of wheat chloroplast protein complexes. First, comprehensive centrifugation methods were utilized for the exhaustive isolation of thylakoid, envelope, and stromal fractions. Second, 1% n-dodecyl-beta-D-maltoside was selected from a series of detergents as the optimal detergent to dissolve protein complexes effectively from membranes. Then, blue native polyacrylamide gel electrophoresis (BN-PAGE) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were improved to separate and analyze the protein complexes. By this systematic strategy, envelopes, thylakoids, and stromata were enriched effectively from chloroplasts in the same process, and more than 18 complexes were obtained simultaneously by BN-PAGE. Finally, thylakoid protein complexes were further analyzed by BN/SDS-PAGE, and nine complex bands and 40 protein spots were observed on BN-PAGE and SDS-PAGE respectively. Our results indicate that this new strategy can be used efficiently to analyze the proteome of chloroplast protein complexes and can be applied conveniently to the analysis of other subcellular protein complexes. PMID- 22056445 TI - Effective cytochrome P450 (CYP) inhibitor isolated from thyme (Thymus saturoides) purchased from a Japanese market. AB - A highly polymethylated flavone that effectively inhibited cytochrome P450s (CYPs) 1A2 and 3A4 (IC(50) = 2.41 and 1.71 uM) in vitro was isolated from thyme leaves (Thymus saturoides) purchased from a Japanese market. Its structure was spectroscopically identified as 4',5-dihydroxy-3',6,7,8-tetramethoxy flavone (8 methoxycirsilineol, 1). This is the first report describing a strong inhibitor of CYP1A2 and 3A4 isolated from Thymus saturoides. PMID- 22056446 TI - TPS1 terminator increases mRNA and protein yield in a Saccharomyces cerevisiae expression system. AB - Both terminators and promoters regulate gene expression. In Saccharomyces cerevisiae, the TPS1 terminator (TPS1t), coupled to a gene encoding a fluorescent protein, produced more transgenic mRNA and protein than did similar constructs containing other terminators, such as CYC1t, TDH3t, and PGK1t. This suggests that TPS1t can be used as a general terminator in the development of metabolically engineered yeast in high-yield systems. PMID- 22056447 TI - Comparative profiling analysis of central metabolites in Euglena gracilis under various cultivation conditions. AB - Comparative metabolic profiling analysis was performed to investigate light- and aeration-dependent regulation of central metabolism in Euglena gracilis. The metabolic profiles of E. gracilis were significantly altered in response to changes in aeration conditions. While many glycolytic intermediates and amino acids accumulated in aerobically grown E. gracilis, a significant reduction in these metabolites was observed for cells under anaerobic conditions, which resulted in elevated production of wax ester. PMID- 22056448 TI - 1,2-Di-O-alpha-linolenoyl-3-O-beta-galactosyl-sn-glycerol as a superoxide generation inhibitor from Perilla frutescens var. crispa. AB - Using a superoxide (O(2)(-)) generation assay system with differentiated HL-60 cells, 1,2-di-O-alpha-linolenoyl-3-O-beta-galactosyl-sn-glycerol (DLGG) was identified as an O(2)(-) generation inhibitor from Perilla frutescens var. crispa (a local variety, kida-chirimen shiso). DLGG suppressed the O(2)(-) level in a dose-dependent manner with an IC(50) value of 21 uM, comparable to those of rosmarinic acid (RoA, IC(50) = 29 uM) and caffeic acid (CA, IC(50) = 30 uM). While RoA and CA also dose-dependently inhibited O(2)(-) generation in a xanthine xanthine oxidase system, DLGG had no effect in the same system. Thus DLGG appeared to decrease the O(2)(-) level in the HL-60 assay system by mechanisms different from those of RoA and CA, which appeared to act as O(2)(-) scavengers. PMID- 22056449 TI - Thraustochytrid Aurantiochytrium sp. 18W-13a accummulates high amounts of squalene. AB - Here we report on the 18W-13a strain of Aurantiochytrium sp., which accumulates very high amounts of squalene. The squalene contents and production at 4 d of culture were 198 mg/g and 1.29 +/- 0.13 g/L, respectively, exceptionally high values compared to previous reports. PMID- 22056450 TI - Effect of a 0.6% energy trans fatty acid intake on serum cholesterol concentrations in healthy young Japanese subjects. AB - A randomized crossover study in healthy young Japanese showed no significant effects of a 0.6% energy trans fatty acid (TFA) intake on the serum cholesterol concentrations and parameters of glucose metabolism. The results indicate that TFAs at this dietary level may have no adverse metabolic effects on healthy young Japanese. PMID- 22056451 TI - Functional analysis of the cyclopiazonic acid biosynthesis gene cluster in Aspergillus oryzae RIB 40. AB - The cyclopiazonic acid (CPA) nonproducing strain, Aspergillus oryzae RIB 40, does not biosynthesize cyclo-acetoacetyl-L-tryptophan (cAATrp) due to a truncation in the responsible PKS-NRPS gene. We found that RIB 40 converted cAATrp to 2 oxocyclopiazonic acid, the final product of CPA biosynthesis in A. oryzae. This indicates that the CPA biosynthesis gene cluster, except for the PKS-NRPS gene, is functional in RIB 40. PMID- 22056452 TI - Biological activity and stability of mangosteen as a potential natural color. AB - Mangosteen pericarp color indicates antioxidant activity relating to the concentration of phenolics and flavonoids. The extract moderately inhibited Bacilus subtilis and was found to be stable at a concentration of 1.0 mg/mL at pH 3 at 23 degrees C over 7 d. Mangosteen pericarp extracts can therefore be used in pharmaceutical products that require low to medium pH. PMID- 22056453 TI - Selection of Shewanella oneidensis MR-1 gene-knockout mutants that adapt to an electrode-respiring condition. AB - Mutants of Shewanella oneidensis MR-1 that adapted to an electrode-respiring condition were selected from a random transposon-insertion mutant library to obtain active current-generating mutants and identify relevant cellular components. The mutants were selected in the presence of an electrode (poised at +0.2 V vs. an Ag/AgCl reference electrode) as the sole electron acceptor, and they were isolated on agar plates. Transposon-insertion sites in the isolated mutants were identified by inverse PCR coupled to sequence analyses. Southern blotting using a transposon probe was also performed to detect mutants that grew abundantly on the electrode. These analyses revealed that in many isolated mutants transposons were inserted in genes relevant to the synthesis of cell surface structures, including SO_3350 (pilus synthesis), SO_3171 (polysaccharide synthesis), SO_3174 (polysaccharide synthesis), and SO_0165 (general secretion pathway). In microbial fuel cells, some of these (the SO_3350 and SO_4704 mutants) generated higher electrical outputs than wild-type MR-1, while the others generated lower outputs. The results suggest that cell-surface structures have a large influence on microbial current generation. PMID- 22056454 TI - Antidiabetic effects of Vigna nakashimae extract in db/db mice. AB - The inhibitory activity of Vigna nakashimae extract against intestinal alpha glucosidase was investigated in vitro and in vivo. The extract exerted a significant inhibitory effect against intestinal alpha-glucosidases. With sucrose loading, it reduced the peak responses of blood glucose significantly in normal mice. Next, it was administrated to 8-week-old db/db mice for 2 weeks, and then plasma glucose, triglyceride, and total cholesterol levels were measured. The extract significantly suppressed postprandial hyperglycemia and blood glycated hemoglobin in the db/db mice. In addition, it lowered fasting glucose and improved glucose tolerance. Furthermore, it led to significant decreases in plasma triglyceride levels. It reduced endoplasmic reticulum stress in thapsigargin-induced HepG2 cells. Taken together, these results suggest that Vigna nakashimae extract has hypoglycemic and hypolipidemic effects that occur via inhibition of alpha-glucosidase activity and endoplasmic reticulum stress. PMID- 22056455 TI - Use of bottom ash of waste coal as an effective microbial carrier. AB - An experiment was done to determine the efficacy of waste bottom ash as an effective microbial carrier. Bottom ash found to be a suitable microbial carrier. The average of viable cells of Paenibacillus polymyxa GS01 (as a test biocontrol agent) in bottom ash samples was about 10(8) cfu/10 +/- 2 mg. The surface of bottom ash coated with 5% PVA w/v was most effective for improvement of cell viability. TSB medium containing 50 mg/L of MnSO(4) . H(2)O was the best for spore production of P. polymyxa GS01. Thus waste bottom ash coating with 5% PVA is likely to be suitable for use as a microbial carrier. PMID- 22056456 TI - Screening of optimal cellulases from symbiotic protists of termites through expression in the secretory pathway of Saccharomyces cerevisiae. AB - For direct and efficient ethanol production from cellulosic materials, we screened optimal cellulases from symbiotic protists of termites through heterologous expression with Saccharomyces cerevisiae. 11 cellulases, belonging to glycoside hydrolase families 5, 7, and 45 endoglucanases (EGs), were confirmed to produce with S. cerevisiae for the first time. A recombinant yeast expressing SM2042B24 EG I was more efficient at degrading carboxylmethyl cellulose than was Trichoderma reesei EG I, a major EG with high cellulolytic activity. PMID- 22056457 TI - Consistent multi-time-point brain atrophy estimation from the boundary shift integral. AB - Brain atrophy measurement is increasingly important in studies of neurodegenerative diseases such as Alzheimer's disease (AD), with particular relevance to trials of potential disease-modifying drugs. Automated registration based methods such as the boundary shift integral (BSI) have been developed to provide more precise measures of change from a pair of serial MR scans. However, when a method treats one image of the pair (typically the baseline) as the reference to which the other is compared, this systematic asymmetry risks introducing bias into the measurement. Recent concern about potential biases in longitudinal studies has led to several suggestions to use symmetric image registration, though some of these methods are limited to two time-points per subject. Therapeutic trials and natural history studies increasingly involve several serial scans, it would therefore be useful to have a method that can consistently estimate brain atrophy over multiple time-points. Here, we use the log-Euclidean concept of a within-subject average to develop affine registration and differential bias correction methods suitable for any number of time-points, yielding a longitudinally consistent multi-time-point BSI technique. Baseline, 12 month and 24-month MR scans of healthy controls, subjects with mild cognitive impairment and AD patients from the Alzheimer's Disease Neuroimaging Initiative are used for testing the bias in processing scans with different amounts of atrophy. Four tests are used to assess bias in brain volume loss from BSI: (a) inverse consistency with respect to ordering of pairs of scans 12 months apart; (b) transitivity consistency over three time-points; (c) randomly ordered back-to back scans, expected to show no consistent change over subjects; and (d) linear regression of the atrophy rates calculated from the baseline and 12-month scans and the baseline and 24-month scans, where any additive bias should be indicated by a non-zero intercept. Results indicate that the traditional BSI processing pipeline does not exhibit significant bias due to its use of windowed sinc interpolation, but with linear interpolation and asymmetric registration, bias can be pronounced. Either improved interpolation or symmetric registration alone can greatly reduce this bias, and our proposed method combining both aspects shows no significant bias in any of the four experiments. PMID- 22056458 TI - Multi-echo acquisition. AB - The rapid development of fMRI was paralleled early on by the adaptation of MR spectroscopic imaging (MRSI) methods to quantify water relaxation changes during brain activation. This review describes the evolution of multi-echo acquisition from high-speed MRSI to multi-echo EPI and beyond. It highlights milestones in the development of multi-echo acquisition methods, such as the discovery of considerable gains in fMRI sensitivity when combining echo images, advances in quantification of the BOLD effect using analytical biophysical modeling and interleaved multi-region shimming. The review conveys the insight gained from combining fMRI and MRSI methods and concludes with recent trends in ultra-fast fMRI, which will significantly increase temporal resolution of multi-echo acquisition. PMID- 22056459 TI - Dynamical stability of intrinsic connectivity networks. AB - Functional connectivity MRI (fcMRI) has become a widely used technique in recent years for measuring the static correlation of activity between cortical regions. Using a publicly available resting state dataset (n = 961 subjects), we obtained high spatial-resolution maps of functional connectivity between a lattice of 7266 regions covering the gray matter. Average whole brain functional correlations were calculated, with high reproducibility within the dataset and across sites. Since correlation measures not only represent pairwise connectivity information, but also shared inputs from other brain regions, we approximate pairwise connection strength by representing each region as a linear combination of the others by performing a Cholesky decomposition of the pairwise correlation matrix. We then used this weighted connection strength between regions to iterate relative brain activity in discrete temporal steps, beginning both with random initial conditions, and with initial conditions reflecting intrinsic connectivity networks using each region as a seed. In whole brain simulations based on weighted connectivity from healthy adult subjects (mean age 27.3), there was consistent convergence to one of two inverted states, one representing high activity in the default mode network, the other representing low relative activity in the default mode network. Metastable intermediate states in our simulation corresponded to combinations of characterized functional networks. Convergence to a final state was slowest for initial conditions on the borders of the default mode network. PMID- 22056460 TI - Structure Tensor Informed Fiber Tractography (STIFT) by combining gradient echo MRI and diffusion weighted imaging. AB - Structural connectivity research in the human brain in vivo relies heavily on fiber tractography in diffusion-weighted MRI (DWI). The accurate mapping of white matter pathways would gain from images with a higher resolution than the typical ~2mm isotropic DWI voxel size. Recently, high field gradient echo MRI (GE) has attracted considerable attention for its detailed anatomical contrast even within the white and gray matter. Susceptibility differences between various fiber bundles give a contrast that might provide a useful representation of white matter architecture complementary to that offered by DWI. In this paper, Structure Tensor Informed Fiber Tractography (STIFT) is proposed as a method to combine DWI and GE. A data-adaptive structure tensor is calculated from the GE image to describe the morphology of fiber bundles. The structure tensor is incorporated in a tractography algorithm to modify the DWI-based tracking direction according to the contrast in the GE image. This GE structure tensor was shown to be informative for tractography. From closely spaced seedpoints (0.5mm) on both sides of the border of 1) the optic radiation and inferior longitudinal fasciculus 2) the cingulum and corpus callosum, STIFT fiber bundles were clearly separated in white matter and terminated in the anatomically correct areas. Reconstruction of the optic radiation with STIFT showed a larger anterior extent of Meyer's loop compared to a standard tractography alternative. STIFT in multifiber voxels yielded a reduction in crossing-over of streamlines from the cingulum to the adjacent corpus callosum, while tracking through the fiber crossings of the centrum semiovale was unaffected. The STIFT method improves the anatomical accuracy of tractography of various fiber tracts, such as the optic radiation and cingulum. Furthermore, it has been demonstrated that STIFT can differentiate between kissing and crossing fiber configurations. Future investigations are required to establish the applicability in more white matter pathways. PMID- 22056461 TI - The contribution of myelin to magnetic susceptibility-weighted contrasts in high field MRI of the brain. AB - T(2)*-weighted gradient-echo MRI images at high field (>= 7T) have shown rich image contrast within and between brain regions. The source for these contrast variations has been primarily attributed to tissue magnetic susceptibility differences. In this study, the contribution of myelin to both T(2)* and frequency contrasts is investigated using a mouse model of demyelination based on a cuprizone diet. The demyelinated brains showed significantly increased T(2)* in white matter and a substantial reduction in gray-white matter frequency contrast, suggesting that myelin is a primary source for these contrasts. Comparison of in vivo and in-vitro data showed that, although tissue T(2)* values were reduced by formalin fixation, gray-white matter frequency contrast was relatively unaffected and fixation had a negligible effect on cuprizone-induced changes in T(2)* and frequency contrasts. PMID- 22056462 TI - Quantitative functional MRI: concepts, issues and future challenges. AB - Since its inception 20 years ago, functional magnetic resonance imaging (fMRI) of the human brain based on the blood oxygenation level dependent (BOLD) contrast phenomenon has proliferated and matured. Today it is the predominant functional brain imaging modality with the majority of applications being in basic cognitive neuroscience where it has primarily been used as a tool to localize brain activity. While the magnitude of the BOLD response is often used in these studies as a surrogate for the level of neuronal activity, the link between the two is, in fact, quite indirect. The BOLD response is dependent upon hemodynamic (blood flow and volume) and metabolic (oxygen consumption) responses as well as acquisition details. Furthermore, the relationship between neuronal activity and the hemodynamic response, termed neurovascular coupling, is itself complex and incompletely understood. Quantitative fMRI techniques have therefore been developed to measure the hemodynamic and metabolic responses to modulations in brain activity. These methods have not only helped clarify the behaviour and origins of the BOLD signal under normal physiological conditions but they have also provided a potentially valuable set of tools for exploring pathophysiological conditions. Such quantitative methods will be critical to realize the potential of fMRI in a clinical context, where simple BOLD measurements cannot be uniquely interpreted, and to enhance the power of fMRI in basic neuroscience research. In this article, recent advances in human quantitative fMRI methods are reviewed, outstanding issues discussed and future challenges and opportunities highlighted. PMID- 22056463 TI - Similar behaviour, different brain patterns: age-related changes in neural signatures of ignoring. AB - We measured behavioural performance and fMRI activity whilst old and young adults performed a temporal segmentation task ('preview search'). Being able to select parts of the visual world to be attended or ignored is a critical visual skill. Both old and young adults were able to improve their performance on a difficult search task when some of the distracter items were presented earlier than the remainder. Comparisons of brain activity and functional connectivity, however, suggested that the underlying mechanisms are quite different for the two age groups. Older adults' activation patterns do not correspond to those predicted by simple increased involvement of frontal regions reflecting higher demand with age but seem to suggest that changes in brain activation patterns propagate throughout the cortex. PMID- 22056464 TI - On-farm treatment of dairy soiled water using aerobic woodchip filters. AB - Dairy soiled water (DSW) is produced on dairy farms through the washing-down of milking parlours and holding areas, and is generally applied to land. However, there is a risk of nutrient loss to surface and ground waters from land application. The aim of this study was to use aerobic woodchip filters to remove organic matter, suspended solids (SS) and nutrients from DSW. This novel treatment method would allow the re-use of the final effluent from the woodchip filters to wash down yards, thereby reducing water usage and environmental risks associated with land spreading. Three replicate 100 m(2) farm-scale woodchip filters, each 1 m deep, were constructed and operated to treat DSW from 300 cows over an 11-month study duration. The filters were loaded at a hydraulic loading rate of 30 L m(-2) d(-1), applied in four doses through a network of pipes on the filter surface. Average influent concentrations of chemical oxygen demand (COD), SS and total nitrogen (TN) of 5750 +/- 1441 mg L(-1), 602 +/- 303 mg L(-1) and 357 +/- 100 mg L(-1), respectively, were reduced by 66, 86 and 57% in the filters. Effluent nutrient concentrations remained relatively stable over the study period, indicating the effectiveness of the filter despite increasing and/or fluctuating influent concentrations. Woodchip filters are a low cost, minimal maintenance treatment system, using a renewable resource that can be easily integrated into existing farm infrastructure. PMID- 22056465 TI - Breakage and re-growth of flocs: effect of additional doses of coagulant species. AB - Several polyaluminum chloride (PACl) coagulants were prepared, with different OH/Al ratios (B values), and characterized by Ferron assay. These were used in studies of floc formation, breakage and re-growth with kaolin suspensions under controlled shear conditions, using a continuous optical monitoring method. Particular attention was paid to the effect of small additional coagulant dosages, added during the floc breakage period, on the re-growth of broken flocs. The results showed that the re-growth ability was greatly dependent on the nature of the PACl species added as second coagulant. The re-growth ability of broken flocs was greatest when the second coagulant was PACl(0) (i.e. AlCl(3), with B = 0) and least with PACl(25) (B = 2.5). In the latter case there was no effect on floc re-growth, irrespective of the initial coagulant used. PACls with intermediate B values gave some improvement in floc re-growth, but less than that with PACl(0). Additional dosage of PACl(0) gave re-grown flocs about the same size or even larger than those before breakage. The re-growth of broken flocs is significantly correlated with the species Al(a) (monomeric) and Al(b) (polymeric), as determined by Ferron assay. The amorphous hydroxide precipitate formed from PACl(0), (mainly Al(a)) can greatly improve the adhesion between broken flocs and give complete re-growth. However, for PACl(25), mostly composed of Al(b), the nature of the precipitate is different and there is no effect on floc re-growth. PMID- 22056466 TI - Assessing the benefits of focal pair cryo-electron tomography. AB - Cryo electron tomography provides nanometer-scale information on biological matter preserved in a close-to native state. The resolution of tomograms and structures resolved by sub-tomogram averaging is typically limited by the contrast transfer function of the electron microscope, which is especially critical for thick samples. Here, we report a method to increase the attainable resolution by recording tomographic 'focal pairs', which are pairs of tilt series of the same object acquired in complementary defocus conditions. Low defocus imaging provides high resolution at low contrast, while high defocus imaging yields high contrast at the price of limited resolution. Quantitative assessment of the quality of lipid bilayer reconstructions in the resulting tomograms demonstrates stable resolution preservation beyond 3 nm for cells thicker than 500 nm. Further, in computational simulations on synthetic datasets we show the applicability of the method to sub-tomogram averaging, demonstrating its potential for achieving higher resolution. PMID- 22056467 TI - Formins filter modified actin subunits during processive elongation. AB - Fission yeast cells reject actin subunits tagged with a fluorescent protein from the cytokinetic contractile ring, so cytokinesis fails and the cells die when the native actin gene is replaced by GFP-actin. The lack of a fluorescent actin probe has prevented a detailed study of actin filament dynamics in contractile rings, and left open questions regarding the mechanism of cytokinesis. To incorporate fluorescent actin into the contractile ring to study its dynamics, we introduced the coding sequence for a tetracysteine motif (FLNCCPGCCMEP) at 10 locations in the fission yeast actin gene and expressed the mutant proteins from the native actin locus in diploid cells with wild-type actin on the other chromosome. We labeled these tagged actins inside live cells with the FlAsH reagent. Cells incorporated some of these labeled actins into actin patches at sites of endocytosis, where Arp2/3 complex nucleates all of the actin filaments. However, the cells did not incorporate any of the FlAsH-actins into the contractile ring. Therefore, formin Cdc12p rejects actin subunits with a tag of ~2 kDa, illustrating the stringent structural requirements for this formin to promote the elongation of actin filament barbed ends as it moves processively along the end of a growing filament. PMID- 22056468 TI - Cryo-EM study of Hepatitis B virus core antigen capsids decorated with antibodies from a human patient. AB - The capsid (core antigen, HBcAg) is one of three major antigens present in patients infected with Hepatitis B virus. The capsids are icosahedral particles, whose most prominent features are spikes that extend 25 A out from the contiguous "floor". At the spike tip are two copies of the "immunodominant loop". Previously, the epitopes of seven murine monoclonal antibodies have been identified by cryo-EM analysis of Fab-labeled capsids. All but one are conformational and all but one map around the spike tip. The exception, which is also the tightest-binder, straddles an inter-molecular interface on the floor. Seeking to relate these observations to the immunological response of infected humans, we isolated anti-cAg antibodies from a patient, prepared Fabs, and analyzed their binding to capsids. A priori, one possibility was that many different Fabs would give an undifferentiated continuum of Fab-related density. In fact, the density observed was highly differentiated and could be reproduced by modeling with just five Fabs, three binding to the spike and two to the floor. These results show that epitopes on the floor, far (~30 A) from the immunodominant loop, are clinically relevant and that murine anti-cAg antibodies afford a good model for the human system. PMID- 22056469 TI - Seasonal and H1N1v influenza vaccines in MS: safety and compliance. AB - BACKGROUND: Viral infections may induce exacerbation of multiple sclerosis (MS), and attempts should be made to prevent them in MS patients by means of vaccines, but immunization is considered to possibly trigger autoimmune disease activity. AIMS: We studied the safety and patient compliance of seasonal influenza and H1N1v influenza vaccines. METHODS: Clinical data on 101 consecutive patients with MS who participated in the study conducted between December, 2009 and February, 2010 were retrieved from the patients' charts. They all filled in a questionnaire on demographics, clinical symptoms and, when applicable, date of being vaccinated for seasonal influenza and/or H1N1v influenza. RESULTS: Five of the 49 vaccinated patients reported side effects of fever or flu-like symptoms associated with the administration of either of the vaccines: there were no complications or need for hospitalization. No patient reported any new neurological symptoms following the use of either vaccine. It emerged that many MS patients did not receive at least one of the vaccines, and that a substantial number of physicians were unsure of how to advise on vaccinations. CONCLUSIONS: Our results are intended to help reassure patients with MS and their physicians about the safety of seasonal influenza and H1N1v influenza vaccines. PMID- 22056470 TI - Detection of nuclear matrix protein 22 and survivin baseline level in patients after radical cystectomy. AB - We investigated the baseline levels of urine nuclear matrix protein 22 (U-NMP22) and survivin in urine after radical cystectomy for primary invasive bladder cancer. We measured U-NMP22 and survivin values in 72 patients with four types of urinary diversion (Indiana bladder, Bricker bladder, Mainz bladder and orthotopic bladder) after radical cystectomy and 25 healthy volunteers. We also analyzed the relation between the U-NMP22 and survivin level and other variables among patients with continent urinary diversion and incontinent urinary diversion as well as healthy controls, and found that the U-NMP22 and survivin values were not associated with postoperative interval or gender. The U-NMP22 values (mean +/- standard error) for continent urinary diversion, incontinent urinary diversion and healthy controls were 12.08 +/- 0.10, 16.62 +/- 0.15 and 0.01 +/- 0.00 U/ml, respectively. The survivin values (mean +/- standard error) for continent urinary diversion, incontinent urinary diversion and healthy controls were 0.47 +/- 0.06, 0.69 +/- 0.16 and 0.02 +/- 0.03 U/ml, respectively. The U-NMP22 and survivin values in the Bricker bladder group were significantly higher than the values in the other three groups. We noted that increased levels of U-NMP22 and survivin after radical cystectomy varied according to different predictors, which may be useful for designing strategies to follow these cases. PMID- 22056471 TI - Morphology and hemodynamics during vascular regeneration in critically ischemic murine skin studied by intravital microscopy techniques. AB - BACKGROUND: With the understanding of angiogenesis and arteriogenesis, new theories about the orchestration of these processes have emerged. The aim of this study was to develop an in vivo model that enables visualization of vascular regenerating mechanisms by intravital microscopy techniques in collateral arteriolar flap vascularity. METHODS: A dorsal skin flap (15 * 30 mm) was created in mice and fixed into a skinfold chamber to allow for assessment of morphology and microhemodynamics by intravital fluorescence microscopy (IVFM). Laser scanning confocal microscopy (LSCM) was utilized for three-dimensional reconstruction of the microvascular architecture. RESULTS: Flap tpO(2) was 5.3 +/ 0.9 versus 30.5 +/- 1.2 mm Hg in controls (p < 0.01). The collateral arterioles in the flap tissue were dilated (29.4 +/- 5.3 MUm; p < 0.01 vs. controls) and lengthened in a tortuous manner (tortuosity index 1.00 on day 1 vs. 1.35+/- 0.05 on day 12; p < 0.01). Functional capillary density was increased from 121.00 +/- 25 to 170 +/- 30 cm/cm(2) (day 12; p < 0.01) as a result of angiogenesis. Morphological evidence of angiogenesis on capillary level and vascular remodeling on arteriolar level could be demonstrated by IVFM and LSCM. CONCLUSIONS: Present intravital microscopy techniques offer unique opportunities to study structural changes and hemodynamic effects of vascular regeneration in this extended axial pattern flap model. PMID- 22056472 TI - Differential regulation of RGS proteins in the prefrontal cortex of short- and long-term human opiate abusers. AB - Opiate addiction is characterized by drug tolerance and dependence which involve adaptive changes in MU-opioid receptors (MORs) signaling. Regulators of G-protein signaling RGS9, RGS4 and RGS10 proteins negatively regulate G(alphai/o) protein activity modulating MOR function. An important role of RGS proteins in drug addiction has been described but the status of RGS proteins in human brain of opiate addicts remains unknown. The present study evaluated the immunoreactivity levels of RGS4, RGS9 and RGS10 proteins in prefrontal cortex of short- (n = 15) and long-term (n = 21) opiate abusers and in matched control subjects. RGS4 protein was not altered in short-term opiate abusers but, in long-term abusers it was significantly up-regulated (Delta = 29 +/- 6%). RGS10 protein expression was significantly decreased in short-term (Delta = -42 +/- 7%) but remained unaltered in long-term opiate abusers. RGS9 protein levels in opiate abusers did not differ from matched controls either in the short-term or in the long-term opiate abuser groups. RGS4, RGS9 and RGS10 levels were also studied in brains (frontal cortex) of rats submitted to acute and chronic morphine treatment and to spontaneous and naloxone-precipitated opiate withdrawal. Chronic morphine treatment in rats was associated with an increase in RGS4 protein immunoreactivity (Delta = 28 +/- 7%), which persisted in spontaneous (Delta = 35 +/- 8%) and naloxone-precipitated withdrawal (Delta = 30 +/- 9%) without significant changes in RGS9 and RGS10 proteins. The specific modulation of RGS4 and RGS10 protein expression observed in the prefrontal cortex of opiate abusers might be relevant in the neurobiology of opiate tolerance, dependence and withdrawal. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22056473 TI - Novel markers of cerebral embolism in the course of infective endocarditis. PMID- 22056474 TI - Achievement of lipoprotein goals among patients with metabolic syndrome at high cardiovascular risk across Europe. The EURIKA study. AB - OBJECTIVE: To examine for the first time the achievement of lipoprotein treatment goals in patients with metabolic syndrome and lipid abnormalities who are at elevated cardiovascular risk in Europe. METHODS: Cross-sectional study conducted in 2009-2010 in 12 European countries among outpatients aged >=50 years free of clinical cardiovascular disease. We assessed achievement of American Diabetes Association/American College of Cardiology lipid treatment goals in those with metabolic syndrome at highest risk (diabetes plus >=1 additional major cardiovascular risk factor beyond lipid abnormalities) or high risk (no diabetes but >=2 additional major cardiovascular risk factors). RESULTS: Among 1431 highest-risk patients, 64.6% (between-country range [BCR] 40-84.5%) were on lipid lowering medication. Of them, 13.4% (BCR: 2.5-28.6%) had LDL-cholesterol<70 mg/dl, non-HDL-cholesterol<100mg/dl, and apolipoprotein B<80 mg/dl. Among 832 high-risk patients, 38.7% BCR: 27.5-55.3%) were on lipid-lowering medication. Of them, 20.5% (BCR: 5.5-57.6%) had LDL-cholesterol<100mg/dl, non-HDL cholesterol<130 mg/dl, and apolipoprotein B<90 mg/dl. About 96% of highest-risk patients and 94% of high-risk patients were given at least one lifestyle advice (weight reduction, healthy diet, physical activity, no-smoking), but only 1.3% of the former and 4.9% of the latter reached all three lipid goals. CONCLUSION: There is a substantial gap between clinical guidelines and medical practice since only one in 5-7 patients met all treatment targets. Although most patients received lifestyle advice, the effectiveness of counseling was very low. Large between-country differences in outcomes suggest considerable room for improvement. PMID- 22056475 TI - Evaluation of coronary artery stent patency by using 64-slice multi-detector computed tomography and conventional coronary angiography: a comparison with intravascular ultrasonography. AB - BACKGROUND: Most studies have investigated the diagnostic accuracy of 64-slice multi-detector computed tomography (MDCT) to detect coronary artery stent patency by using conventional coronary angiography (CCA) as the reference standard. In this study, we compared the diagnostic accuracy of MDCT and CCA by using intravascular ultrasonography (IVUS) as the reference standard. METHODS: Forty six patients with previously implanted coronary artery stents (n=87) underwent MDCT followed by CCA and IVUS within 24h. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) of MDCT and CCA for detecting or excluding in-stent diameter restenosis (ISDR) by using in-stent area restenosis (ISAR) and minimal luminal area (MLA) <=4.0 mm(2) of IVUS as the reference standard were determined. RESULTS: Eight stents (9%) were judged non evaluable using MDCT for the detection of ISDR. ISDR was detected in 28% (22/79) of the evaluable stents using CCA. When ISAR was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 71%, 96%, 91% and 86%, and the corresponding values for CCA were 64%, 96%, 90% and 83%. When MLA <=4.0mm(2) was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 87%, 96%, 91% and 95%, and for CCA were 78%, 96%, 90% and 92%. CONCLUSIONS: When ISAR with MLA <=4.0 mm(2)was detected on IVUS, CCA and MDCT had similar diagnostic accuracies for ISDR detection. High specificity and NPV make 64-slice MDCT a reliable non-invasive method for excluding ISDR. PMID- 22056476 TI - Cardiac rupture in tako-tsubo cardiomyopathy with persistent ST-segment elevation. PMID- 22056477 TI - The traveling salesrat: insights into the dynamics of efficient spatial navigation in the rodent. AB - Rodent spatial navigation requires the dynamic evaluation of multiple sources of information, including visual cues, self-motion signals and reward signals. The nature of the evaluation, its dynamics and the relative weighting of the multiple information streams are largely unknown and have generated many hypotheses in the field of robotics. We use the framework of the traveling salesperson problem (TSP) to study how this evaluation may be achieved. The TSP is a classical artificial intelligence NP-hard problem that requires an agent to visit a fixed set of locations once, minimizing the total distance traveled. We show that after a few trials, rats converge on a short route between rewarded food cups. We propose that this route emerges from a series of local decisions that are derived from weighing information embedded in the context of the task. We study the relative weighting of spatial and reward information and establish that, in the conditions of this experiment, when the contingencies are not in conflict, rats choose the spatial or reward optimal solution. There was a trend toward a preference for space when the contingencies were in conflict. We also show that the spatial decision about which cup to go to next is biased by the orientation of the animal. Reward contingencies are also shown to significantly and dynamically modulate the decision-making process. This paradigm will allow for further neurophysiological studies aimed at understanding the synergistic role of brain areas involved in planning, reward processing and spatial navigation. These insights will in turn suggest new neural-like architectures for the control of mobile autonomous robots. PMID- 22056478 TI - Carrier depletion and exciton diffusion in a single ZnO nanowire. AB - Carrier depletion and transport in a single ZnO nanowire Schottky device have been investigated at 5 K, using cathodoluminescence measurements. An exciton diffusion length of 200 nm has been determined along the nanowire axis. The depletion width is found to increase linearly with the reverse bias. The origin of this unusual dependence in semiconductor material is discussed in terms of charge location and dimensional effects on the screening of the junction electric field. PMID- 22056479 TI - Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells. AB - Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive agents. Several studies have indicated the important role of dendritic cells (DCs), highly specialized antigen-presenting and immunomodulatory cells, in GC mediated suppression of adaptive immune responses. Recently, we demonstrated that triiodothyronine (T3) has potent immunostimulatory effects on bone marrow-derived mouse DCs through a mechanism involving T3 binding to cytosolic thyroid hormone receptor (TR) beta1, rapid and sustained Akt activation and IL-12 production. Here we explored the impact of GCs on T3-mediated DC maturation and function and the intracellular events underlying these effects. Dexamethasone (Dex), a synthetic GC, potently inhibited T3-induced stimulation of DCs by preventing the augmented expression of maturation markers and the enhanced IL-12 secretion through mechanisms involving the GC receptor. These effects were accompanied by increased IL-10 levels following exposure of T3-conditioned DCs to Dex. Accordingly, Dex inhibited the immunostimulatory capacity of T3-matured DCs on naive T-cell proliferation and IFN-gamma production while increased IL-10 synthesis by allogeneic T cell cultures. A mechanistic analysis revealed the ability of Dex to dampen T3 responses through modulation of Akt phosphorylation and cytoplasmic-nuclear shuttling of nuclear factor-kappaB (NF-kappaB). In addition, Dex decreased TRbeta1 expression in both immature and T3-maturated DCs through mechanisms involving the GC receptor. Thus GCs, which are increased during the resolution of inflammatory responses, counteract the immunostimulatory effects of T3 on DCs and their ability to polarize adaptive immune responses toward a T helper (Th)-1-type through mechanisms involving, at least in part, NF kappaB- and TRbeta1-dependent pathways. Our data provide an alternative mechanism for the anti-inflammatory effects of GCs with critical implications in immunopathology at the cross-roads of the immune-endocrine circuits. PMID- 22056480 TI - Prospective analysis of association between use of statins or other lipid lowering agents and colorectal cancer risk. AB - PURPOSE: To determine whether 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) are associated with a decreased risk of colorectal cancer. METHODS: The population included 159,219 postmenopausal women enrolled in the Women's Health Initiative in which 2000 pathologically confirmed cases of colorectal cancer were identified during an average of 10.7 (S.D. 2.9) years. Information on statins was collected at baseline and years 1, 3, 6, and 9. Self- and interviewer administered questionnaires were used to collect information on other risk factors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the use of Cox proportional hazards regression to evaluate the relationship between statin use and risk. Statistical tests were two-sided. RESULTS: Statins were used by 12,030 (7.6%) women at baseline. The annualized colorectal cancer rate was 0.13% among users and 0.12% among nonusers. The multivariable adjusted HR for users versus nonusers was 0.99 (95% confidence interval [CI], 0.83-1.20, p = .95), and 0.79 (95% CI, 0.56-1.11) for users of >=3 years. In the multivariable adjusted time-dependent model, the HR for lovastatin was 0.62 (95% CI, 0.39 0.99). There was no effect of tumor location, stage or grade. CONCLUSIONS: There was a reduction in colorectal cancer risk associated with lovastatin and a nonsignificant association with longer duration of use. PMID- 22056481 TI - Infant growth and onset of puberty: prospective observations from Hong Kong's "Children of 1997" birth cohort. AB - PURPOSE: Infant growth and early puberty are associated with the risk of cardiovascular disease. It is unclear whether pubertal timing has an independent etiologic role or is a marker of preceding growth. We examined whether infant growth was associated with age at pubertal onset and whether any associations were mediated by childhood height or body mass index. METHODS: We used multivariable interval-censored proportional hazards regression in 6873 term births (87% follow-up, 53% male) from a population-representative Hong Kong Chinese birth cohort, "Children of 1997." We examined the adjusted associations of sex-specific infant growth trajectories, derived from latent class analyses by the use of, on average, 4.2 measurements per child, with clinically assessed age at pubertal onset (Tanner stage II). We used Sobel tests to assess mediation. RESULTS: Compared with children of average birth weight whose weight followed the same centile curve, a faster weight growth trajectory from birth to 12 months was associated with earlier pubertal onset (time ratio, 0.979; 95% confidence interval, 0.965-0.993) among boys, whereas girls born light with slow infant growth had later puberty (time ratio 1.020, 95% confidence interval 1.006-1.034). These associations were mediated by both height and body mass index among girls but only by height in boys. CONCLUSIONS: Infant weight growth may be associated with earlier pubertal onset, particularly in boys, at least in part because it is associated with more linear growth in childhood. Earlier pubertal onset may be an indicator of up-regulation of growth axes related to the risk of cardiovascular disease. PMID- 22056482 TI - Lectin-induced activation of plasma membrane NADPH oxidase in cholesterol depleted human neutrophils. AB - The gp91phox subunit of flavocytochrome b(558) is the catalytic core of the phagocyte plasma membrane NADPH oxidase. Its activation occurs within lipid rafts and requires translocation of four subunits to flavocytochrome b(558). gp91phox is the only glycosylated subunit of NADPH oxidase and no data exist about the structure or function of its glycans. Glycans, however, bind to lectins and this can stimulate NADPH oxidase activity. Given this information, we hypothesized that lectin-gp91phox interactions would facilitate the assembly of a functionally active NADPH oxidase in the absence of lipid rafts. To test this, we used lectins with different carbohydrate-binding specificity to examine the effects on H(2)O(2) generation by human neutrophils treated with the lipid raft disrupting agent methyl-beta-cyclodextrin (MbetaCD). MbetaCD treatment removed membrane cholesterol, caused changes in cell morphology, inhibited lectin-induced cell aggregation, and delayed lectin-induced assembly of the NADPH oxidase complex. More importantly, MbetaCD treatment either stimulated or inhibited H(2)O(2) production in a lectin-dependent manner. Together, these results show selectivity in lectin binding to gp91phox, and provide evidence for the biochemical structures of the gp91phox glycans. Furthermore, the data also indicate that in the absence of lipid rafts, neutrophil NADPH oxidase activity can be altered by these select lectins. PMID- 22056483 TI - Cocaine administration increases angiotensin I-converting enzyme (ACE) expression and activity in the rat striatum and frontal cortex. AB - Some central effects of cocaine administration seem to be related to angiotensin II (Ang II) or its metabolites. Nonetheless, it is still an open question whether or not the levels of angiotensin I-converting enzyme (ACE), the main Ang II generating enzyme, are modified by cocaine administration. To evaluate the effect of acute and subchronic cocaine administration on ACE activity and mRNA expression, male rats were randomly assigned to saline or cocaine group. Acute and subchronic cocaine administration induced a significant increase in ACE activity and mRNA expression in the frontal cortex and striatum but not in the hippocampus. These results suggest that some of the Ang II related effects of cocaine upon the central nervous system can be mediated by changes on the expression and activity of ACE in the striatum and frontal cortex. PMID- 22056484 TI - Abeta plaque-associated glial reaction as a determinant of apoptotic neuronal death and cortical gliogenesis: a study in APP mutant mice. AB - The purpose of this study was to investigate the microglia-driven apoptosis and the Abeta deposits triggered generation of new microglial cells in the neocortex of TgCRND8 mice. Three- and seven-month-old TgCRND8 mice, displaying an early and widespread amyloid deposition, respectively, were used. In 7-month-old TgCRND8 mice the Abeta-associated glial reaction was accompanied by an intense immunoreactivity of both TNF-alpha and inducible nitric oxide synthase, increased immunoreactivity of the pro-apoptotic protein Bax and a decrease in levels of the anti-apoptotic protein Bcl-2.Cortical and hippocampal neurons of TgCRND8 mice displayed higher immunoreactivity and higher nuclear expression of the transcription factor NF-kB than controls. It is possible that such an increase could represent a defence/compensatory response to degeneration. These findings indicate that Abeta deposits activate brain-resident microglia population and astrocytes, and induce overproduction of inflammatory mediators that enhance pro- and anti-apoptotic cascades. In both 3- and 7-month-old TgCRND8 mice apparent gliogenesis was present in the vicinity of Abeta plaques in the neocortex, indicating that microglia have a high proliferative rate which might play a more complex role than previously acknowledge. PMID- 22056485 TI - Neuroprotective effects of melatonin on the nigrostriatal dopamine system in the zitter rat. AB - Melatonin has ubiquitous actions, both as a direct free-radical scavenger and as an indirect anti-oxidant. The present study examined in vivo neuroprotective effects of melatonin on the nigrostriatal dopaminergic system in zitter (zi/zi) rat, which displays abnormal metabolism of superoxide leading to age-related degeneration of the dopaminergic system. For up to 9 months after weaning, zi/zi rats had ad libitum access to drinking water containing melatonin. Chronic treatment with melatonin attenuated the decreases of dopamine and its metabolite in zi/zi rat caudate-putamen (CPU). Immunohistochemistry for tyrosine hydroxylase (TH) was consistent with neurochemical data in the CPU and demonstrated substantial sparing of the reduction of TH-immunoreactive neurons in the substantia nigra pars compacta. Quantitative polymerase chain reaction (qPCR) was performed to analyze mRNA expressions of pro-inflammatory cytokines (IL-1beta and TNF-alpha) and the anti-oxidant enzymes (catalase (CAT), superoxide dismutase (SOD) 1 and 2, and glutathione peroxidase (GPx1)) in the striatum and midbrain in order to examine the neuroprotective effect of melatonin. IL-1beta and TNF-alpha mRNA expressions were significantly increased in both areas of 3-month-old zi/zi rats, whereas there was a significant decrease in CAT mRNA expression in the striatum of 6-month-old zi/zi rat as compared to age-matched controls. With the exception of the high TNF-alpha mRNA expression in 3-month-old zi/zi midbrains, chronic treatment of melatonin attenuated expressional changes of IL-1beta, CAT, SOD1, and GPx1. These results suggest that besides its direct scavenger effects, chronic melatonin treatment provides a neuroprotective effect against dopaminergic degeneration by suppressing pro-inflammatory cytokines and up regulating anti-oxidant enzyme expression. PMID- 22056486 TI - Magnetic resonance imaging assessment of intraventricular dyssynchrony and delayed enhancement as predictors of response to cardiac resynchronization therapy in patients with heart failure of ischaemic and non-ischaemic etiologies. AB - PURPOSE: To assess the value of dyssynchrony and myocardial viability assessment by cardiac magnetic resonance (CMR) in prediction of response to cardiac resynchronization therapy (CRT) in patients with heart failure (HF) of both ischaemic and non-ischaemic etiologies. MATERIALS AND METHODS: Patients scheduled for CRT in NYHA class II-IV, left ventricular ejection fraction <35%, QRS >= 120 ms were included. Tagged cine and late gadolinium enhancement (LGE) images were performed. Dyssynchrony was assessed with inTag toolbox and LGE was quantified using cutoff value at half of maximal signal in the scar. Cardiopulmonary exercise test, echocardiography and blood testing for NT-proBNP levels were done at baseline and 6 months after CRT. RESULTS: 52 patients (age 60.3 +/- 13 years) were included. 26 patients (50%) met response criteria. The ischaemic etiology of HF was more frequent (69% vs. 31%, p=0.002), the percent of LGE was higher (7.7% [0-13.5%] vs. 19.0% (0-31.9%], p=0.013), regional vector of circumferential strain variance (RVV) was lower (0.27 +/- 0.08 vs. 0.34 +/- 0.09, p=0.009) and uniformity of radial strain was higher (0.72 +/- 0.25 vs. 0.56 +/- 0.29, p=0.046) in non-responders vs. responders. Multivariate logistic regression showed that RVV predicted response to CRT (HR 2.3, 95% CI 1.02-5.02, p=0.0430) independently of LGE and the etiology of heart failure. In the subgroup of patients with ischaemic HF the extend of transmural scar within myocardium was higher in non responders vs. responders (26.3% vs. 15.0% respectively, p=0.01) and was a predictor of response to CRT in univariable analysis (HR 0.87, 95% CI 0.77-0.98, p=0.025) providing the sensitivity of 76% and specificity of 75% at the cutoff point of 18% in the prediction of poor response to CRT. In patients with non ischaemic HF QRS was wider (162 ms vs. 140 ms, p=0.04), regional vector of strain variance (RVV) was higher (0.39 vs. 0.25, p=0.002) and uniformity of radial strain was lower (0.52 vs. 0.80, p=0.049) in non-responders vs. responders. Univariable logistic regression showed that RVV was a predictor of response to CRT (HR 1.50, 95% CI 1.06-2.13, p=0.022), providing the sensitivity of 94% and specificity of 85% at the cutoff point of 0.31. CONCLUSIONS: CMR derived parameters of dyssynchrony such as RVV may provide an additive value in prediction of response to CRT, especially in patients with non-ischaemic etiology of heart failure. In patients with ischaemic HF the transmurality of LGE is an important predictor of lack of response to CRT. PMID- 22056487 TI - Structural and functional cerebral impairments in cirrhotic patients with a history of overt hepatic encephalopathy. AB - OBJECTIVE: Diffuse brain atrophy has been observed in cirrhotic patients and recent reports have revealed the persistence of cognitive impairment after clinical resolution of overt hepatic encephalopathy. We sought to explore the continued influence of overt hepatic encephalopathy on neurological function by measuring brain resting-state inherent connectivity, based on an investigation of structural abnormalities. METHODS: Neuropsychological tests and structural and functional magnetic resonance scanning were conducted in 20 healthy controls and 21 cirrhotic patients with a history of overt hepatic encephalopathy. The analysis of voxel-based morphometry and functional connectivity were performed to detect the alterations in brain structure and function, respectively. RESULTS: Patients showed significantly worse performance in neuropsychological tests as compared with controls, despite apparently normal mental status. Analysis of voxel-based morphometry revealed a decrease in gray matter volume primarily in the midline regions, bilateral insular cortex and caudates, left parahippocampal gyrus, and right cerebellum posterior lobe, while the volume of the bilateral thalamus showed an increase. Of these regions, the posterior cingulate cortex with peak atrophy was selected as the origin for the analysis of functional connectivity. Typical patterns of a default mode network were identified in both groups. Decreased functional connectivity was found in the medial prefrontal gyrus, left inferior parietal lobule, and left middle temporal gyrus in the patients. CONCLUSIONS: Both functional and structural impairments were evident after apparent recovery from overt hepatic encephalopathy, demonstrating that brain dysfunction induced by hepatic encephalopathy persisted after clinical resolution and provided a basis for further evolution of the disease. PMID- 22056488 TI - Predictors of mother-daughter resemblance in dietary intake. The role of eating styles, mothers' consumption, and closeness. AB - The present study examined the resemblance between daughters' and mothers' intake of energy-dense food (EDF) and vegetables as perceived by daughters and the potential moderating influence of relationship closeness. One-hundred and twelve female first-year psychology students (aged 17-25 years) completed an online measure incorporating questions on demographic information, food frequency, eating style, and mother-daughter closeness. The EDF and vegetable consumption of daughters and their perception of their mothers' consumption were significantly related. Daughters who ate more EDF perceived that their mothers consumed more EDF and vegetables overall and had lower levels of restrained eating. Both mothers' consumption of vegetables (as perceived by daughters) and the number of meals consumed within the family home had a strong influence on daughters' vegetable intake. Closeness of the mother-daughter relationship did not moderate the relationship between the EDF or vegetable intake of mothers and daughters. Overall, these findings are consistent with the contention that mothers may have a significant influence on the EDF consumption and vegetable intake of their young adult daughters. The mechanism of this influence requires further investigation. PMID- 22056489 TI - Family characteristics predicting favourable changes in 10 and 11-year-old children's lifestyle-related health behaviours during an 18-month follow-up. AB - Lifestyle-related health behaviours such as screen time, physical activity, sleep duration, and food intake tend to change into non-favourable directions when children become young adolescents. Cross-sectional studies show that family characteristics are important determinants for children's health behaviours. This study examined whether family characteristics such as parenting practices at meals and family involvement predict a more favourable change in children's lifestyle-related health behaviours during an 18-month follow-up. 745 children in school grades 4 and 5 (response rate 65%) filled in a baseline questionnaire in the autumn of 2006. A follow-up was conducted in the spring of 2008 (91%). Several health behaviours had changed in a non-favourable direction. Baseline parenting practices at meals and family involvement predicted some of the changes in the lifestyle-related health behaviours in 2008. Parenting practices at meals predicted a smaller increase in TV, DVD viewing time, and a smaller decrease in fruit intake. Amongst family involvement determinants, less time alone at home after school predicted a smaller increase in screen time, a smaller decrease in sleep duration, and a smaller increase in soft drink intake. For conclusion several family characteristics predicted favourable changes in children's lifestyle-related health behaviours. PMID- 22056490 TI - Risk factors and in-hospital mortality in Chinese patients undergoing coronary artery bypass grafting: analysis of a large multi-institutional Chinese database. AB - OBJECTIVE: This study was undertaken to delineate outcomes and to assess risk factors for in-hospital mortality among Chinese patients undergoing coronary artery bypass grafting. METHODS: From 2007 to 2008, a total of 9838 consecutive adult patients undergoing coronary artery bypass grafting were enrolled in the Chinese Coronary Artery Bypass Grafting Registry, which included 43 centers from 17 province-level regions in China. This registry collected information on 67 preoperative factors and 30 operative factors believed to influence in-hospital mortality. The relationship between risk factors and in-hospital mortality was evaluated by univariate and logistic regression analyses. RESULTS: Overall in hospital mortality was 2.5%. Eleven risk factors were found to be significant predictors for outcome: age (continuous), body mass index (continuous), left ventricular ejection fraction (continuous), preoperative New York Heart Association functional class III or IV, chronic renal failure, extracardiac arteriopathy, chronic obstructive pulmonary disease, preoperative atrial fibrillation or flutter (within 2 weeks), preoperative critical state, other than elective surgery, and combined valve procedure. Calibration with the Hosmer Lemeshow test was satisfactory (P=.35), and the discrimination power was good (area under the receiver operating characteristic curve, 0.81; 95% confidence interval, 0.79-0.84). CONCLUSIONS: The risk profiles and in-hospital mortality of Chinese patients undergoing coronary artery bypass grafting were determined from data in the most up-to-date multi-institutional database. Eleven variables were demonstrated to be independent risk factors for in-hospital death after coronary artery bypass grafting. PMID- 22056491 TI - Differentiating aortic fibrosarcoma from acute intramural hematoma. PMID- 22056493 TI - Uric acid and blood pressure. PMID- 22056492 TI - Phylogeny, diversity, and species delimitation of the North American Round-Nosed Minnows (Teleostei: Dionda), as inferred from mitochondrial and nuclear DNA sequences. AB - Accurate delimitation of species is a critical first step in protecting biodiversity. Detection of distinct species is especially important for groups of organisms that inhabit sensitive environments subject to recent degradation, such as creeks, springs, and rivers in arid or semi-desert regions. The genus Dionda currently includes six recognized and described species of minnows that live in clear springs and spring-fed creeks of Texas, New Mexico (USA), and northern Mexico, but the boundaries, delimitation, and characterization of species in this genus have not been examined rigorously. The habitats of some of the species in this genus are rapidly deteriorating, and many local populations of Dionda have been extirpated. Considering the increasing concerns over degradation of their habitat, and pending a more detailed morphological revision of the genus, we undertook a molecular survey based on four DNA regions to examine variation over the range of the genus, test species boundaries, and infer phylogenetic relationships within Dionda. Based on analyses of two mitochondrial (cytb and D loop) and two nuclear (Rag1 and S7) DNA regions from specimens collected throughout the range of Dionda, we identified 12 distinct species in the genus. Formerly synonymized names are available for two of these species, and four other species remain undescribed. We also redefine the known range of six species. The limited distribution of several of the species, coupled with widespread habitat degradation, suggests that many of the species in this genus should be targets for conservation and recovery efforts. PMID- 22056494 TI - Comparative study of surgical margins and cosmetic outcome in lumpectomy versus segmental resection in breast cancer. AB - OBJECTIVE: The aim of the present retrospective study was to compare two breast conserving techniques, segmental resection and standard lumpectomy, for the treatment of breast cancer regarding their oncological safety. Quality of life aspects were evaluated by assessing the respective postsurgical cosmetic results. PATIENTS AND METHODS: 190 women with breast cancer located in the superior and lateral quadrant were included in the study. Sixty patients were treated with segmental resection (group 1), whereas 130 underwent standard lumpectomy (group 2). Tumor sizes were determined and excised tissue specimens were analyzed for positive or negative resection margins. Patients were given a 16-item questionnaire for the postsurgical self-assessment of the cosmetic outcome. RESULTS: No statistically significant difference was found concerning the number of positive resection margins between the groups (25 vs. 30%, p = 0.46). Exceptions were ventral margins, which predominated in group 2 (p = 0.016). Group 1 revealed a significantly larger maximum tumor size with negative margins as compared to group 2 (26.6 vs. 17.0 mm). General satisfaction with the cosmetic results was comparable between groups. CONCLUSIONS: Segmental resection surgery, as a method of breast conservation therapy, can be used to treat larger breast lesions as compared to standard lumpectomy. PMID- 22056495 TI - Oil droplets do not affect assimilation and survival probability of first feeding larvae of North-East Arctic cod. AB - Oil exploration and production in the Atlantic moves northwards towards spawning and nursery areas of fish species that sustain some of the world's largest fisheries. Models are therefore needed that can simulate the effects of accidental oil spills on early life stages of these fish. In this study, we combined an individual based model and a microcosm approach to infer effects of the water soluble fraction (WSF) and of an oil dispersion (WSF and droplets) on two key endpoints of North East Arctic cod (Gadus morhua) larvae: food assimilation rate and survival probability. Both exposure types (WSF and dispersion) decreased assimilation rate (control: 0.4 d(-1)) and survival probability (control: 0.96) in a concentration-dependent fashion, with EC(50)s of about 2 (feeding) and 40 MUg/L ?PAH in the WSF (survival probability). No consistent differences were found between the ECs from the two exposure types indicating no additional oil droplet effects in the oil dispersion. During post exposure, effects on the two endpoints disappeared, which was confirmed by an image analyses we performed of gut content fluorescence. Our results also show that the larvae model fitted the experimental data from the two exposure types equally well, indicating that the presence of oil droplets did not affect model performance. More complex models that explicitly consider possible mechanisms of oil droplet toxicity - in addition to the toxicity of the WSF - on the two examined endpoints during a 17 day time frame do therefore not have a higher accuracy than simpler models that neglect oil droplet toxicity. PMID- 22056496 TI - Surgical stabilization of postpartum symphyseal instability: two cases and a review of the literature. AB - During pregnancy, asymptomatic widening of the symphysis pubis by about one third is normal and considered physiological. However, peripartal relaxation of the symphyseal and sacroiliac ligaments may cause significant complaints conditions including pain and gait dysfunction. Usually, patients are treated by the application of pelvic binders and bed rest up to several weeks. Surgical stabilization is performed seldom, though it may be promising in selected patients. Based on 2 cases of postpartum symphyseal instability treated by surgical fixation, the current literature was reviewed systematically to evaluate the outcome and potential complications of surgical fixation of symphyseal instability. Thirteen articles met inclusion criteria and were analyzed in detail. Including the two cases presented, surgical stabilization of postpartum symphyseal instability has been described for 33 patients. In conclusion, though only based on case reports and case series, early surgical stabilization represents a decent treatment option for postpartum symphyseal instability and may be indicated by pain or walking disability alone. In regard to the clinical outcome comparing internal and external fixation, no differences were demonstrable. However, the rate of infection was higher in patients treated by external fixation. Based on these data, we propose a treatment algorithm for this injury. PMID- 22056497 TI - Process assessment of a peer education programme for HIV prevention among sex workers in Dhaka, Bangladesh : a social support framework. AB - This study evaluated the process of a peer education program for hotel-based sex workers in Dhaka, Bangladesh, with social support proposed as an organizing framework. Programme outcomes were examined through baseline and follow-up assessments. Sex workers naive to peer education were assessed on socio-cognitive and behavioural variables; a subsample was reassessed at follow-up 23 weeks later on average. Process was assessed in terms of the content of peer education sessions. These sessions were recorded and coded into percentages of social support types provided by the peer educator to her audience: informational, instrumental, appraisal, emotional, companionship, non-support. Peer educators were classified into three "social support profiles" based on average proportions of emotional and informational support they provided. Seeing more peer educators with a high informational support profile was related to higher sex worker self efficacy, self-reported STI symptoms, and self-reported condom use at follow-up; the same was true for the high emotional support profile and treatment seeking. Social support constituted a useful framework, but needs further exploration. This study provided a direct, in-depth examination of the process of peer education based on a comprehensive theoretical framework. PMID- 22056498 TI - Characterization and functional analysis of two PKR genes in fugu (Takifugu rubripes). AB - PKR (protein kinase R) is a serine-threonine kinase that inhibits protein synthesis by the phosphorylation of the eukaryotic translation initiation factor 2-alpha (eIF2alpha), and activates NFkappaB by inducing NFkappaB-inducing kinase and IkappaB (inhibitor of NFkappaB) kinase. This can lead to antiviral and anti proliferative effects. In this study, the complete sequence and organization of two fugu PKR genes (fPKRs) were determined by in silico analysis and conventional PCR. The full-length fPKR1 and fPKR2 genes were 3832 bp and 4325 bp, which encoded 523 and 492 amino acids, respectively. Both encoded two dsRNA binding domains and a Serine/Threonine protein kinase domain, and showed very high similarity to green spotted puffer PKRs. Gene expression of the two fPKRs was measured by quantitative real-time PCR on tissue samples from healthy fish and peripheral blood leukocytes stimulated with polyinosinic:polycytidylic acid (PolyI:C) or lipopolysaccharides (LPS). The fPKRs were highly expressed in the skin and fPKR2 was significantly induced in PBLs by PolyI:C but not by LPS. The fPKRs inhibited translation of a luciferase reporter gene in a dose-dependent manner and induced transcriptional activity of a mammalian NFkappaB luciferase reporter. These results demonstrate that two PKRs in a single species can both be independently, but not equally, functional and support the hypothesis that fish PKRs have roles in the innate immune response similar to those of mammalian PKRs. PMID- 22056499 TI - A second copper zinc superoxide dismutase (CuZnSOD) in the blue crab Callinectes sapidus: cloning and up-regulated expression in the hemocytes after immune challenge. AB - The full-length cDNA (1362 nucleotides, GenBank JF736621) encoding an extracellular copper zinc superoxide dismutase initially isolated from an EST library of the blue crab Callinectes sapidus was characterized using 3' RACE and named Cas-ecCuZnSOD-2. The open reading frame of Cas-ecCuZnSOD-2 contains 203 deduced amino acids with the conserved active catalytic center for copper and zinc binding and the post-translational modification at two putative N glycosylation and nine phosphorylation sites. Overall, the deduced amino acids of Cas-ecCuZnSOD-2 shared only 35% sequence identity with that of Cas-ecCuZnSOD (GenBank AF264031) which was previously found in C. sapidus, while it showed ~75% sequence identity to Scylla paramamosain ecCuZnSOD (GenBank FJ774661). The expression profile of Cas-ecCuZnSOD-2 and the other three C. sapidus SODs: ecCuZn, cytMn- and mitMn SODs was largely ubiquitous among the tested tissues obtained from a juvenile female at intermolt: brain, eyestalk ganglia, pericardial organs, and thoracic ganglia complex (nervous system); hepatopancreas (digestive system); heart, artery and hemocytes (circulatory system); gill and antennal gland (excretory system), hypodermis, and Y-organ (endocrine organ). Our study reports, for the first time in the crustaceans, expression analyses for all four Cas-SODs in hemocytes after immune challenges. Crabs challenged with lipopolysaccharides (LPS) injection had a remarkable induction of Cas-ecCuZnSOD-2 expression along with three other SODs in hemocytes, suggesting that Cas-SODs including Cas-ecCuZnSOD-2 are involved in the defense system, possibly innate immunity and immunocompetency of C. sapidus. PMID- 22056500 TI - Molecular characterisation and expression analysis of a fish-egg lectin in rock bream, and its response to bacterial or viral infection. AB - A fish-egg lectin, RbFEL, was identified from rock bream (Oplegnathus fasciatus) and its expression analysed. In both vertebrates and invertebrates, carbohydrate binding proteins (lectins) play an important role in innate immunity against microbial invasion. Here, we report the cloning of a fish-egg lectin from rock bream using a combination of expression sequence tag (EST) analyses. The full length cDNA of RbFEL is composed of 1512-bp with a 780-bp ORF that encodes 259 amino acid residues. The deduced polypeptide exhibits six conserved residues of the FEL family. All cysteine positions in each domain were completely conserved. Reverse transcription quantitative real-time PCR analysis of the tissues revealed that RbFEL mRNA was abundantly expressed in liver, moderately expressed in head kidney and rarely expressed in other tissues. Expression analyses of time series sampled fertilised eggs showed that expression gradually increased 1, 3, 12, 24 and 36 h after fertilisation. In addition, RbFEL expression was significantly up regulated in rock bream challenged with Edwardsiella tarda, Streptococcus iniae and red sea bream iridovirus (RSIV). These results suggest that RbFEL is a member of the egg-lectin family and is involved in the innate immune response in rock bream. PMID- 22056501 TI - Replication of five prostate cancer loci identified in an Asian population- results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). AB - BACKGROUND: A recent genome-wide association study (GWAS) of prostate cancer in a Japanese population identified five novel regions not previously discovered in other ethnicities. In this study, we attempt to replicate these five loci in a series of nested prostate cancer case-control studies of European ancestry. METHODS: We genotyped five single-nucleotide polymorphism (SNP): rs13385191 (chromosome 2p24), rs12653946 (5p15), rs1983891 (6p21), rs339331 (6p22), and rs9600079 (13q22), in 7,956 prostate cancer cases and 8,148 controls from a series of nested case-control studies within the National cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We tested each SNP for association with prostate cancer risk and assessed whether associations differed with respect to disease severity and age of onset. RESULTS: Four SNPs (rs13385191, rs12653946, rs1983891, and rs339331) were significantly associated with prostate cancer risk (P values ranging from 0.01 to 1.1 * 10(-5)). Allele frequencies and ORs were overall lower in our population of European descent than in the discovery Asian population. SNP rs13385191 (C2orf43) was only associated with low-stage disease (P = 0.009, case-only test). No other SNP showed association with disease severity or age of onset. We did not replicate the 13q22 SNP, rs9600079 (P = 0.62). CONCLUSIONS: Four SNPs associated with prostate cancer risk in an Asian population are also associated with prostate cancer risk in men of European descent. IMPACT: This study illustrates the importance of evaluation of prostate cancer risk markers across ethnic groups. PMID- 22056502 TI - Fine-mapping CASP8 risk variants in breast cancer. AB - BACKGROUND: Multiple genome-wide and candidate gene association studies have been conducted in search of common risk variants for breast cancer. Recent large meta analyses, consolidating evidence from these studies, have been consistent in highlighting the caspase-8 (CASP8) gene as important in this regard. To define a risk haplotype and map the CASP8 gene region with respect to underlying susceptibility variant/s, we screened four genes in the CASP8 region on 2q33-q34 for breast cancer risk. METHODS: Two independent data sets from the United Kingdom and the United States, including 3,888 breast cancer cases and controls, were genotyped for 45 tagging single nucleotide polymorphisms (tSNP) in the expanded CASP8 region. SNP and haplotype association tests were carried out using Monte Carlo-based methods. RESULTS: We identified a three-SNP haplotype across rs3834129, rs6723097, and rs3817578 that was significantly associated with breast cancer (P < 5 * 10(-6)), with a dominant risk ratio and 95% CI of 1.28 (1.21 1.35) and frequency of 0.29 in controls. Evidence for this risk haplotype was extremely consistent across the two study sites and also consistent with previous data. CONCLUSION: This three-SNP risk haplotype represents the best characterization so far of the chromosome upon which the susceptibility variant resides. IMPACT: Characterization of the risk haplotype provides a strong foundation for resequencing efforts to identify the underlying risk variant, which may prove useful for individual-level risk prediction, and provide novel insights into breast carcinogenesis. PMID- 22056503 TI - Early-life factors and breast cancer risk in Hispanic women: the role of adolescent body size. AB - BACKGROUND: Adult body size has long been known to influence breast cancer risk, and there is now increasing evidence that childhood and adolescent body size may also play a role. METHODS: We assessed the association with body size at ages 10, 15, and 20 years in 475 premenopausal and 775 postmenopausal Hispanic women who participated in a population-based case-control study of breast cancer conducted from 1995 to 2004 in the San Francisco Bay Area. We used unconditional logistic regression to estimate ORs and 95% CIs for the associations with self-reported relative weight compared with peers and body build at ages 10, 15, and 20 years. RESULTS: In premenopausal women, we found inverse associations with relative weight compared with peers, with ORs of 0.63 (P(trend) = 0.05), 0.31 (P(trend) < 0.01), and 0.44 (P(trend) = 0.02) for heavier versus lighter weight at ages 10, 15, and 20 years, respectively. These inverse associations were stronger in currently overweight women and U.S.-born women and did not differ significantly for case groups defined by estrogen receptor status. In postmenopausal women, not currently using hormone therapy, inverse associations with relative weight were limited to U.S.-born Hispanics. CONCLUSIONS: Large body size at a young age may have a long-lasting influence on breast cancer risk in premenopausal, and possibly postmenopausal, Hispanic women that is independent of current body mass index. IMPACT: These findings need to be weighed against adverse health effects associated with early-life obesity. PMID- 22056504 TI - Measured body mass index in adolescence and the incidence of colorectal cancer in a cohort of 1.1 million males. AB - BACKGROUND AND AIMS: The increasing prevalence of adolescent obesity affects adult health. We investigated the association of adolescent overweight with colorectal cancer incidence in a large cohort of males. METHODS: Body mass index (BMI) was measured in 1.1 million Jewish Israeli males who underwent a general health examination at ages 16 to 19 between 1967 and 2005. Overweight was defined as BMI >= 85th percentile of the standard U.S. distribution in adolescence. Colorectal cancer was identified by linkage with the Israel National Cancer Registry up to 2006. The mean follow-up period was 17.6 +/- 10.9 years, reflecting 19.5 million person-years. Cox proportional hazards modeling was used. RESULTS: The prevalence of adolescent overweight increased from 9.9% to 16.8% in the first 10 and last 10 annual examination cohorts. Colon (n = 445) and rectal cancer (n = 193) cases were detected. Overweight predicted an increased risk of colon cancer [HR = 1.53; 95% confidence interval (CI), 1.17-2.02, P = 0.002] but not of rectal cancer (HR = 1.09; 95% CI, 0.38-1.73, P = 0.72). The risk was greatest for nonmucinous adenocarcinoma of the colon (HR = 1.68, 95% CI, 1.26 2.23, P = 0.001). The association of BMI >= 85th percentile with colon cancer was even more pronounced in analyses that were restricted to men followed until at least 40 years of age [N = 367,478; HR = 1.75 (95% CI, 1.33-2.3, P < 0.001)]. CONCLUSIONS: Adolescent overweight is substantially associated with colon cancer incidence in young to middle-aged adults. IMPACT: These long-term sequelae add to the urgency to seriously address increasing childhood and adolescent obesity with its attendant increasing population impact. PMID- 22056505 TI - Fear and happiness in the eyes: an intra-cerebral event-related potential study from the human amygdala. AB - We present the response pattern of intracranial event-related potentials (ERPs) recorded from depth-electrodes in the human amygdala (four patients) to faces or face parts encoding fearful, happy or neutral expressions. The amygdala showed increased amplitude ERPs (from 200 to 400 ms post-stimulus) in response to the eye region of the face compared to whole faces and to the mouth region. In particular, a strong emotional valence effect was observed, both at group and at single-subject level, with a preferential response to fearful eyes respect to every other stimulus category from 200 to 400 ms after stimulus presentation. A preferential response to smiling eyes compared to happy faces and smiling mouths was also observed at group level from 300 to 400 ms post-stimulus presentation. A complementary time-frequency analysis was performed showing that an increase in the theta frequency band (4-7 Hz) accounted for the main event-related band power (ERBP) change during the 200-500 ms post stimulus interval. The analysis of the ERBPs changes according to their emotional valence showed a strong increase in theta ERBP to fearful eyes, which was higher respect to any other facial stimulus. Moreover, theta ERBP increase to "smiling eyes" was larger respect with that evoked by smiling mouths and whole happy faces. Minimal post-stimulus ERBPs changes were evoked by neutral stimuli. These data are consistent with a special role of the amygdala in processing facial signals, both with negative and positive valence, conveyed by the eye region of the face. PMID- 22056506 TI - Audiovisual integration in low vision individuals. AB - Behavioral and neurophysiological studies have shown an enhancement of visual perception in crossmodal audiovisual stimulation conditions, both for sensitivity and reaction times, when the stimulation in the two sensory modalities occurs in condition of space and time congruency. The purpose of the present work is to verify whether congruent visual and acoustic stimulations can improve the detection of visual stimuli in people affected by low vision. Participants were asked to detect the presence of a visual stimulus (yes/no task) either presented in isolation (i.e., unimodal visual stimulation) or simultaneously with auditory stimuli, which could be placed in the same spatial position (i.e., crossmodal congruent conditions) or in different spatial positions (i.e., crossmodal incongruent conditions). The results show for the first time audiovisual integration effects in low vision individuals. In particular, it has been observed a significant visual detection benefit in the crossmodal congruent as compared to the unimodal visual condition. This effect is selective for visual stimulation that occurs in the portion of visual field that is impaired, and disappears in the region of space in which vision is spared. Surprisingly, there is a marginal crossmodal benefit when the sound is presented at 16 degrees far from the visual stimulus. The observed crossmodal effect seems to be determined by the contribution of both senses to a model of optimal combination, in which the most reliable provides the highest contribution. These results, indicating a significant beneficial effect of synchronous and spatially congruent sounds in a visual detection task, seem very promising for the development of a rehabilitation approach of low vision diseases based on the principles of multisensory integration. PMID- 22056507 TI - Drive latencies in hypoglossal motoneurons indicate developmental change in the brainstem respiratory network. AB - The respiratory rhythm originates and diverges from the brainstem to drive thousands of motoneurons that are responsible for control of the diaphragm, intercostals and upper airway. These motoneurons are known to have a wide range of phase relationships, even within a single motoneuron pool. The proposed source of this rhythm, the preBotzinger complex (preBotC), responds to an array of developmental changes in the first days post-birth, specifically at postnatal day 3 (P3). We hypothesize that such developmental changes in the preBotC have a direct effect on motoneuron phase relationships and should be detectable around age P3. To test our hypothesis, we obtained single- and dual-voltage-clamp recordings of hypoglossal motoneurons in an in vitro slice preparation. We introduce a novel approach to analyzing the phase relationships between motoneurons by using cross-correlation analysis to determine the drive latencies. This analysis reveals that the distribution of drive latencies undergoes a significant change at or before age P3. We use a computational model of the in vitro slice to demonstrate the observed phase differences and hypothesize that network heterogeneity alone may not be sufficient to explain them. Through simulations, we show the effects on the preBotC of different network characteristics such as clustering and common inputs. PMID- 22056508 TI - Synthesis, characterization, and finite size effects on electrical transport of nanoribbons of the charge density wave conductor NbSe3. AB - NbSe(3) exhibits remarkable anisotropy in most of its physical properties and has been a model system for studies of quasi-one-dimensional charge density wave (CDW) phenomena. Herein, we report the synthesis, characterization, and electrical transport of single-crystalline NbSe(3) nanoribbons by a facile one step vapour transport process involving the transport of selenium powder onto a niobium foil substrate. Our investigations aid the understanding of the CDW nature of NbSe(3) and the growth process of the material. They also indicate that NbSe(3) nanoribbons have enhanced CDW properties compared to those of the bulk phase due to size confinement effects, thus expanding the search for new mesoscopic phenomena at the nanoscale level. Single nanoribbon measurements of the electrical resistance as a function of temperature show charge density wave transitions at 59 and 141 K. We also demonstrate significant enhancement in the depinning effect and sliding regimes mainly attributed to finite size effects. PMID- 22056509 TI - Phosphorylation of the arginine/serine repeats of lamin B receptor by SRPK1 insights from molecular dynamics simulations. AB - BACKGROUND: Arginine/serine (RS) repeats are found in several proteins in metazoans with a wide variety of functions, many of which are regulated by SR protein kinase 1 (SRPK1)-mediated phosphorylation. Lamin B receptor (LBR) is such a protein implicated in chromatin anchorage to the nuclear envelope. METHODS: Molecular dynamics simulations were used to investigate the conformation of two LBR peptides containing four (human-) and five (turkey-orthologue) consecutive RS dipeptides, in their unphosphorylated and phosphorylated forms and of a conserved peptide, in isolation and in complex with SRPK1. GST pull-down assays were employed to study LBR interactions. RESULTS: Unphosphorylated RS repeats adopt short, transient helical conformations, whereas serine phosphorylation induces Arginine-claw-like structures. The SRSRSRSPGR peptide, overlapping with the LBR RS repeats, docks into the known, acidic docking groove of SRPK1, in an extended conformation. Phosphorylation by SRPK1 is necessary for the association of LBR with histone H3. CONCLUSIONS: The C-terminal region of the LBR RS domain constitutes a recognition platform for SRPK1, which uses the same recognition mechanism for LBR as for substrates with long RS domains. This docking may promote unfolding of the RS repeats destined to be phosphorylated. Phosphorylation induces Arginine-claw-like conformations, irrespective of the RS repeat length, that may facilitate interactions with basic partners. GENERAL SIGNIFICANCE: Our results shed light on the conformational preferences of an important class of repeats before and after their phosphorylation and support the idea that even short RS domains may be constituents of recognition platforms for SRPK1, thus adding to knowledge towards a full understanding of their phosphorylation mechanism. PMID- 22056510 TI - Terminal differentiation program of skeletal myogenesis is negatively regulated by O-GlcNAc glycosylation. AB - BACKGROUND: O-Linked beta-N-acetylglucosaminylation (O-GlcNAcylation) on the Ser/Thr residue of nucleocytoplasmic proteins is a dynamic post-translational modification found in multicellular organisms. More than 500 proteins involved in a wide range of cellular functions, including cell cycle, transcription, epigenesis, and glucose sensing, are modified with O-GlcNAc. Although it has been suggested that O-GlcNAcylation is involved in the differentiation of cells in a lineage-specific manner, its role in skeletal myogenesis is unknown. METHODS AND RESULTS: A myogenesis-dependent drastic decrease in the levels of O-GlcNAcylation was found in mouse C2C12 myoblasts. The global decrease in O-GlcNAcylation was observed at the earlier stage of myogenesis, prior to myoblast fusion. Genetic or pharmacological inactivation of O-GlcNAcase blocked both the myogenesis-dependent global decrease in O-GlcNAcylation and myoblast fusion. Although inactivation of O-GlcNAcase affected neither cell-cycle exit nor cell survival in response to myogenic stimulus, it perturbed the expression of myogenic regulatory factors. While the expression of myod and myf5 in response to myogenic induction was not affected, that of myogenin and mrf4 was severely inhibited by the inactivation of O-GlcNAcase. CONCLUSION: These results indicate that the terminal differentiation program of skeletal myogenesis is negatively regulated by O-GlcNAcylation. GENERAL SIGNIFICANCE: O-GlcNAcylation is involved in differentiation in a cell lineage-dependent manner, and a decrease in O-GlcNAcylation may have a common role in the differentiation of cells of muscle lineage. PMID- 22056511 TI - Protective effects of allopurinol against acute liver damage and cirrhosis induced by carbon tetrachloride: modulation of NF-kappaB, cytokine production and oxidative stress. AB - BACKGROUND: The aim of this work was to evaluate the hepatoprotective ability of allopurinol to prevent the liver injury induced by carbon tetrachloride (CCl(4)). METHODS: Acute liver damage was induced with CCl(4) (4g/kg, by gavage); allopurinol (50mg/kg, by gavage) was given 1h before and 1h after CCl(4) intoxication and two daily doses for the previous three days. Cirrhosis was established by CCl(4) administration (0.4g/kg, i. p. three times a week, eight weeks); allopurinol was administered (100mg/kg, by gavage, daily) during the long term of CCl(4) treatment. Alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gamma-GTP), xanthine oxidase (XO), lipid peroxidation, reduced and oxidized glutathione (GSH, GSSG, respectively), hydroxyproline and histopathologycal analysis were performed. Nuclear factor-kappaB (NF-kappaB), pro inflammatory and anti-inflammatory cytokines, transforming growth factor-beta (TGF-beta) and metalloproteinase-13 (MMP-13) were analyzed by Western blots. RESULTS: Acute injury increased ALT and gamma-GTP activities, additionally enhanced NF-kappaB nuclear translocation and cytokines production such as tumor necrosis factor-alpha, interleukine-1beta, and interleukine-6. Allopurinol partially prevented these effects, while increased interleukine-10. Acute and chronic CCl(4) treatments altered the levels of XO activity, lipid peroxidation, and GSH/GSSG ratio, while these remained within normal range with allopurinol administration. Necrosis, fibrosis and TGF-beta production induced in chronic injury were partially prevented by allopurinol, interestingly, this drug induced MMP-13 activity. CONCLUSIONS: Allopurinol possesses antioxidant, anti inflammatory and antifibrotic properties, probably by its capacity to reduce NF kappaB nuclear translocation and TGF-beta expression, as well as to induce MMP 13. General significance Allopurinol might be effective treatment of liver diseases. PMID- 22056512 TI - A method for the making and utility of gadolinium-labeled albumin microbubbles. AB - OBJECTIVE: Perfluorocarbon-exposed sonicated dextrose albumin microbubbles (PESDA) binds scavenger receptors and can be noninvasively imaged. To enhance imaging, gadolinium (Gd)-labeled PESDA was developed and tested in a model of vascular inflammation by magnetic resonance imaging (MRI). METHODS AND RESULTS: Purified human serum albumin (HSA) (5%) was labeled with Gd via the covalent binding of diethylenetriaminepentacetic acid. Abdominal aortic tissues in Sprague Dawley rats (n=5 per group) were analyzed by 7-T MRI and scanning electron microscopy to evaluate PESDA binding. Labeling-purified 5% human albumin resulted in an average of 16.1 Gd atoms per albumin molecule as determined by atomic absorption. Forty-eight hours after balloon angioplasty, aortic tissue was enhanced with Gd-PESDA as compared to control tissue. 7-T MRI of explanted tissues was sensitive to the detection of retained PESDA. Enhancement of aortic tissue in vivo was present albeit to a lesser extent than explanted tissue from the same animals. CONCLUSIONS: HSA was successfully labeled, and an albumin-based microbubble with Gd was synthesized. This contrast agent, Gd-PESDA, may serve as an additional agent for the MRI evaluation of innate inflammation and used to noninvasively image early vascular pathophysiologic processes. CONDENSED ABSTRACT: In this study, Gd-PESDA microbubbles and were synthesized and shown to detect the binding of these microbubbles using MRI in injured aortic tissue. The method for synthesizing Gd-PESDA is detailed, and the proposed utility of this new contrast agent is discussed. PMID- 22056513 TI - Neuroendocrine and metabolic activities of ghrelin gene products. AB - Acylated ghrelin (AG) is a 28 amino acid gastric peptide a natural ligand for the growth hormone secretagogue (GHS) receptor type 1a (GHS-R1a), endowed with GH secreting and orexigenic properties. Besides, ghrelin exerts several peripheral metabolic actions, including modulation of glucose homeostasis and stimulation of adipogenesis. Notably, AG administration causes hyperglycemia in rodents as in humans. Ghrelin pleiotropy is supported by a widespread expression of the ghrelin gene, of GHS-R1a and other unknown ghrelin binding sites. The existence of alternative receptors for AG, of several natural ligands for GHS-R1a and of acylation-independent ghrelin non-neuroendocrine activities, suggests that there might be a complex 'ghrelin system' not yet completely explored. Moreover, the patho-physiological implications of unacylated ghrelin (UAG), and obestatin (Ob), the other two ghrelin gene-derived peptides, need to be clarified. Within the next few years, we may better understand the 'ghrelin system', where we might envisage clinical applications. PMID- 22056514 TI - Histomorphological features of the pancreatic remnant as independent risk factors for postoperative pancreatic fistula: a matched-pairs analysis. AB - BACKGROUND/AIMS: Postoperative pancreatic fistula (POPF) is a major complication after resective pancreatic surgery. This study aimed to identify histomorphological features of the pancreatic remnant as independent determinants for the development of POPF. METHODS: Twenty-five patients, 3.6% of 696 resections over a period of 5 years, who developed POPF were matched for age, gender, diagnosis, comorbidities, surgeon and procedure with 25 controls without POPF. Pancreatic duct size and index, fibrosis grade, fat content, edema, and signs of chronic and acute inflammation were measured in frozen sections of the resection margin and were then compared. RESULTS: The POPF rate was 12.2 and 2.6% after distal pancreatectomy and pancreatoduodenectomy, respectively. The POPF group was characterized by a longer ICU and total postoperative stay, higher rate of reoperations and complications. Their pancreata were softer at palpation (88 vs. 56%). Their pancreatic duct was smaller (2.5 vs. 3.2 mm) and their pancreatic fat content higher (16 vs. 8%). High inter- and intralobular fat content, small duct size, low interlobular fibrosis grade and lack of signs of chronic pancreatitis were predictors of POPF development. A score including these parameters identified high-risk patients with a sensitivity of 92% and a specificity of 84%. CONCLUSION: Histomorphological features of the pancreatic remnant play an independent role as risk factors for the development of POPF. A simple histological score based on the frozen sections may already intraoperatively predict the risk of POPF development. PMID- 22056515 TI - Polysplenia syndrome. PMID- 22056516 TI - Thoughts on the incidence of deep organ space/surgical site abscesses following laparoscopy for non-complicated acute appendicitis: A new decision tree. PMID- 22056517 TI - Functional proton transfer pathways in the heme-copper oxidase superfamily. AB - Heme-copper oxidases (HCuOs) terminate the respiratory chain in mitochondria and most bacteria. They are transmembrane proteins that catalyse the reduction of oxygen and use the liberated free energy to maintain a proton-motive force across the membrane. The HCuO superfamily has been divided into the oxygen-reducing A-, B- and C-type oxidases as well as the bacterial NO reductases (NOR), catalysing the reduction of NO in the denitrification process. Proton transfer to the catalytic site in the mitochondrial-like A family occurs through two well-defined pathways termed the D- and K-pathways. The B, C, and NOR families differ in the pathways as well as the mechanisms for proton transfer to the active site and across the membrane. Recent structural and functional investigations, focussing on proton transfer in the B, C and NOR families will be discussed in this review. PMID- 22056518 TI - The fictile coordination chemistry of cuprous-thiolate sites in copper chaperones. AB - Copper plays vital roles in the active sites of cytochrome oxidase and in several other enzymes essential for human health. Copper is also highly toxic when dysregulated; because of this an elaborate array of accessory proteins have evolved which act as intracellular carriers or chaperones for the copper ions. In most cases chaperones transport cuprous copper. This review discusses some of the chemistry of these copper sites, with a view to some of the structural factors in copper coordination which are important in the biological function of these chaperones. The coordination chemistry and accessible geometries of the cuprous oxidation state are remarkably plastic and we discuss how this may relate to biological function. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. PMID- 22056519 TI - Different motion cues are used to estimate time-to-arrival for frontoparallel and looming trajectories. AB - Estimation of time-to-arrival for moving objects is critical to obstacle interception and avoidance, as well as to timing actions such as reaching and grasping moving objects. The source of motion information that conveys arrival time varies with the trajectory of the object raising the question of whether multiple context-dependent mechanisms are involved in this computation. To address this question we conducted a series of psychophysical studies to measure observers' performance on time-to-arrival estimation when object trajectory was specified by angular motion ("gap closure" trajectories in the frontoparallel plane), looming (colliding trajectories, TTC) or both (passage courses, TTP). We measured performance of time-to-arrival judgments in the presence of irrelevant motion, in which a perpendicular motion vector was added to the object trajectory. Data were compared to models of expected performance based on the use of different components of optical information. Our results demonstrate that for gap closure, performance depended only on the angular motion, whereas for TTC and TTP, both angular and looming motion affected performance. This dissociation of inputs suggests that gap closures are mediated by a separate mechanism than that used for the detection of time-to-collision and time-to-passage. We show that existing models of TTC and TTP estimation make systematic errors in predicting subject performance, and suggest that a model which weights motion cues by their relative time-to-arrival provides a better account of performance. PMID- 22056520 TI - Meiotic silencing by unpaired DNA is expressed more strongly in the early than the late perithecia of crosses involving most wild-isolated Neurospora crassa strains and in self-crosses of N. tetrasperma. AB - Meiotic silencing by unpaired DNA is a presumed RNAi-mediated elimination of the transcripts of any gene that is not properly paired with a homolog in meiosis. Eighty wild-isolated strains of Neurospora crassa were classified into three types based on the apparent strength of meiotic silencing of the bml (beta tubulin) and mei-3 genes in crosses with the ::Bml(r) and ::mei-3 tester strains. "OR" and "Sad" type wild-isolates, respectively, did or did not silence both the genes, whereas the "Esm" type (68 strains) silenced bml but not mei-3(+), suggesting an intermediate strength of silencing. Many wild strains, especially of the Esm type, gave fertile crosses with strains bearing the 148 kbp chromosome segment duplication Dp(EB4) but their crosses with the 405 kbp Dp(IBj5) were barren. Larger Dps might include more genes whose sensitivity to silencing is comparable with that of bml, consequently their crosses with the OR and Esm type strains would be about equally barren, whereas small Dps, with presumably few or no bml-like genes suffer little gene silencing in crosses with Esm and Sad strains and thus remain fertile. Using lollipop-shaped asci as indicators of silencing in crosses of the ::act tester with Esm type strains, and white-spored asci in Neurospora tetrasperma self-crosses heterozygous for an ectopic insertion of the asm-1 gene, we found that meiotic silencing was expressed more strongly in the early but not in the late perithecia of these crosses. PMID- 22056521 TI - Accumulation of P-bodies in Candida albicans under different stress and filamentous growth conditions. AB - Candida albicans is an opportunistic fungal pathogen that grows as budding yeast, pseudohyphal, and hyphal forms. In response to external signals, C. albicans switches rapidly among these forms. mRNA-containing cytoplasmic granules, termed processing bodies (P-bodies), have been reported to accumulate under various environmental stress conditions in diverse species from yeast to mammals. Here, we provide the first microscopic and genetic characterization of P-bodies in C. albicans. The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5'-3' exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated. Various growth conditions, including glucose deprivation, hyperosmotic stress, and heat stress, stimulated the accumulation of P-bodies. In addition, we observed P-body aggregation during hyphal development. The deletion mutant strain edc3/edc3 had a defect in filamentation and exhibited a dramatic reduction in the number of P-bodies. These results suggest that Edc3 plays an essential role in the assembly and maintenance of P-bodies in C. albicans, and that the switch to filamentous growth appears to accompany P-body accumulation. PMID- 22056522 TI - A heme peroxidase of the ascomyceteous lichen Leptogium saturninum oxidizes high redox potential substrates. AB - Lichens belonging to the order Peltigerales display strong activity of multi copper oxidases (e.g. tyrosinase) as well as heme-containing peroxidases. The lichen peroxidase was purified to homogeneity from the thallus of Leptogium saturninum (LsaPOX) by fast protein liquid chromatography and then partially characterized. The oligomeric protein occurs as both 79 kDa dimeric and 42 kDa monomeric forms, and displayed broad substrate specificity. In addition to an ability to oxidize classic peroxidase substrates (e.g. 2,6-dimethoxyphenol), the enzyme could convert recalcitrant compounds such as synthetic dyes (e.g. Azure B and Reactive Blue 5), 4-nitrophenol and non-phenolic methoxylated aromatics (e.g. veratryl alcohol). Comparing LsaPOX with a basidiomycete dye-decolorizing (DyP) type peroxidase from Auricularia auricula-judae showed that the lichen enzyme has a high-redox potential, with oxidation capabilities ranging between those of known plant and fungal peroxidases. Internal peptide fragments show homology (up to 60%) with putative proteins from free-living ascomycetes (e.g. Penicillium marneffei and Neosartorya fischeri), but not to sequences of algal or cyanobacterial peptides or to known fungal, bacterial or plant peroxidases. LsaPOX is the first heme peroxidase purified from an ascomyceteous lichen that may help the organism to successfully exploit the extreme micro-environments in which they often grow. PMID- 22056523 TI - Comment on: "Association between subclinical hypothyroidism and severe diabetic retinopathy in Korean patients with type 2 diabetes". PMID- 22056524 TI - [Reduction of muscle mass mediated by myostatin in an experimental model of pulmonary emphysema]. AB - INTRODUCTION: Among the extrapulmonary manifestations of COPD, dysfunction and loss of muscle mass/weight are those that have the greatest impact on the quality of life of patients. Our objective was to evaluate the molecular mechanisms that are potentially implicated in the limited development of muscle mass in the diaphragm and gastrocnemius of mice with experimentally-induced emphysema. METHODS: An experimental model in mice, in which emphysema was induced by means of the local instillation of elastase (n=6), while saline was administered to the controls (n=7). We determined the levels of oxidative stress, proteolytic systems, signaling pathways, growth factors and cell differentiation (western blot) in the diaphragm and gastrocnemius of all the mice after 34 weeks. RESULTS: Upon comparing the mice with emphysema with the controls, the following findings were observed: (1) lower total body weight and lower weight of the diaphragm and gastrocnemius; (2) in the diaphragm, the levels of protein oxidation were increased, the mitochondrial antioxidant systems reduced, the levels of myostatin and of the ERK1/2 and FoxO1 signaling pathways were higher, and the myosin content was lower (67%); and (3) in the gastrocnemius of the emphysematous mice, the cytosolic antioxidants were decreased and the levels of myostatin and of the JNK and NF-kB signaling pathways were increased. CONCLUSIONS: The reduction of the myosin content observed in the diaphragm of mice with emphysema could explain their smaller size. Oxidative stress, myostatin and FoxO could be implicated in the loss of this structural protein. PMID- 22056525 TI - In vivo imaging of bile accumulation and biliary infarction after common bile duct ligation in rats. AB - Obstructive cholestasis is caused by mechanical constriction or occlusion leading to reduced bile flow. Serious complications such as jaundice and even death may follow. Little is known about the initial phase of cholestasis and its consequences for the hepatic microarchitecture. This in vivo study aimed to characterize the nature and kinetics of developing obstructive cholestasis and focused on areas with biliary stasis and infarction by visualizing the autofluorescence of bile acids using intravital microscopy of the liver over a period of 30 h after bile duct ligation in rats. The innovation resided in performing fluorescence microscopy without applying fluorescent dyes. In animals subjected to obstructive cholestasis, the most significant changes observed in vivo were the concomitant appearance of (1) areas with bile accumulation increasing in size (6 h: 0.163 +/- 0.043, 18 h: 0.180 +/- 0.086, 30 h: 0.483 +/- 0.176 mm(2)/field) and (2) areas with biliary infarction (6 h: 0.011 +/- 0.006, 18 h: 0.010 +/- 0.004, 30 h: 0.010 +/- 0.050 mm(2)/field) as well as (3) a relation between the formation of hepatic lesions and enzyme activity in serum. The sequential in vivo analysis presented herein is a new method for the in vivo visualization of the very early changes in the hepatic parenchyma caused by obstructive cholestasis. PMID- 22056526 TI - Coating conditions matter to collagen matrix formation regarding von Willebrand factor and platelet binding. AB - INTRODUCTION: Von Willebrand factor (VWF) and platelet binding needs a uniform collagen matrix therefore we aimed to find an optimal condition for the preparation of human type-I and type-III collagen matrices. METHOD: The effects of pH, salt and ligand concentration and binding time were tested when collagen matrices were prepared by adsorption. Surface-bound collagen and collagen-bound VWF measured by specific antibodies. Platelet adhesion was tested under flow conditions at a shear rate of 1800s(-1) for 2 min. Matrices and platelets were visualized by atomic force and scanning electron microscope. RESULTS: The extent of human collagens type-I and III binding to the surface was 10 and 4 times greater and binding was maximal under 8-16 hours, when coated from physiological buffer solution versus acid solution. Collagen fibrils were more developed and platelet adhesion was higher, with more organized and denser aggregates. VWF binding was parallel to the surface bound collagen in both collagen types. CONCLUSION: Collagen coating of surfaces for VWF binding and platelet adhesion studies is very variable from acid solution. Our experiments provide evidences that neutralizing the acid and adding NaCl in physiological concentration, thereby facilitating formation of collagen fibril molecules in solution, results in efficient coating of human type-I and type III collagens, which then bind normal VWF equally well. PMID- 22056527 TI - Nanoimprint of dehydrated PEDOT:PSS for organic photovoltaics. AB - We demonstrate the fabrication of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) nanogratings by a dehydration-assisted nanoimprint lithographic technique. Dehydration of PEDOT:PSS increases its cohesion to protect the nanostructures formed by nanoimprinting during demolding, resulting in the formation of high quality nanogratings of 60 nm in height, 70 nm in width and 70 nm in spacing (aspect ratio of 0.86). PEDOT:PSS nanogratings are used as hole transport and an electron blocking layer in blended poly(3 hexylthiophene-2,5-diyl) (P3HT):[6,6]-penyl-C61-butyric-acid-methyl-ester (PCBM) organic photovoltaic devices (OPV), showing enhancement of photocurrent and power efficiency in comparison to OPV devices with non-patterned PEDOT:PSS films. PMID- 22056528 TI - A microPET study of the regional distribution of [11C]-PK11195 binding following temporary focal cerebral ischemia in the rat. Correlation with post mortem mapping of microglia activation. AB - BACKGROUND: Post-stroke microglial activation (MA) may have both neurotoxic and pro-repair effects, particularly in the salvaged penumbra. Mapping MA in vivo is therefore an important goal. 11C-PK11195, a ligand for the 18 kDa translocator protein, is the reference radioligand for MA imaging, but a correlation between the regional distributions of in vivo tracer binding and post mortem MA after stroke, as assessed with PET and immunohistochemistry, respectively, has not been demonstrated so far. Here we performed 11C-PK11195 microPET in a rat model previously shown to induce extensive cortical MA, and determined the correlation between 11C-PK11195 and immunostaining with the CD11 antibody OX42, so as to verify the presence of activated microglia, in a template of PET-resolution size regions-of-interest (ROIs) spanning the whole affected hemisphere. METHODS: Adult spontaneously hypertensive rats underwent 45 min distal middle cerebral artery occlusion and 11C-PK11195 PET at Days 2 and 14 after stroke according to a longitudinal design. Following perfusion-fixation at Day 14, brains were removed and coronally cut for OX42 staining. 11C-PK11195 binding potential (BPND) parametric maps were generated, and in each rat both BP(ND) and OX42 (intensity*extent score) were obtained in the same set of 44 ROIs extracted from a cytoarchitectonic atlas to cover the whole hemisphere. Correlations were computed across the 44 ROIs both within and across subjects. RESULTS: Significant BPND increases were observed in both the infarct and surrounding areas in all rats at day 14; less strong but still significant increases were present at day 2. There were highly significant (all p<0.001) positive correlations, both within and across-subjects, between day 14 BPND values and OX42 scores. CONCLUSIONS: The correlation between Day 14 11C-PK11195 and OX42 across the affected hemisphere from the same brain regions and animals further supports the validity of 11C-PK11195 as an in vivo imaging marker of MA following stroke. The finding of statistically significant increases in 11C-PK11195 as early as 48 h after stroke is novel. These results have implications for mapping MA after stroke, with potential therapeutic applications. PMID- 22056529 TI - The influence of spontaneous activity on stimulus processing in primary visual cortex. AB - Spontaneous activity in the resting human brain has been studied extensively; however, how such activity affects the local processing of a sensory stimulus is relatively unknown. Here, we examined the impact of spontaneous activity in primary visual cortex on neuronal and behavioural responses to a simple visual stimulus, using functional MRI. Stimulus-evoked responses remained essentially unchanged by spontaneous fluctuations, combining with them in a largely linear fashion (i.e., with little evidence for an interaction). However, interactions between spontaneous fluctuations and stimulus-evoked responses were evident behaviourally; high levels of spontaneous activity tended to be associated with increased stimulus detection at perceptual threshold. Our results extend those found in studies of spontaneous fluctuations in motor cortex and higher order visual areas, and suggest a fundamental role for spontaneous activity in stimulus processing. PMID- 22056530 TI - Quantitative PET analyses of regional [11C]PE2I binding to the dopamine transporter--application to juvenile myoclonic epilepsy. AB - The dopamine transporter (DAT) is of central interest in research on the pathophysiology and treatment of neuro-psychiatric disorders. [(11)C]PE2I is an established radioligand that provides high-contrast delineation of brain regions that are rich in DAT. The aim of the present PET study in eight patients with juvenile myoclonic epilepsy (JME) was to evaluate the kinetics of [(11)C]PE2I in the brain and to compare binding parameters with those of age-matched control subjects (n = 6). Each patient participated in 90-minute PET measurements with [(11)C]PE2I. Data were analyzed using kinetic compartment analyses with metabolite-corrected arterial plasma input and reference tissue models using the cerebellum as a reference region. The time-activity curves were well described by the two-tissue compartment model (2TCM) for the DAT-rich regions. The 2TCM with fixed K(1)/k(2) ratio derived from the cerebellum provided robust and reliable estimates of binding potential (BP(ND)) and total distribution volume (V(T)). The reference tissue models also provided robust estimates of BP(ND), although they gave lower BP(ND) values than the kinetic analysis. Compared with those of control subjects, we found that BP(ND) values obtained by all approaches were reduced in the midbrain of the patients with JME. The finding indicates impaired dopamine uptake in the midbrain of JME patients. The three-tissue compartment model could best describe uptake in the cerebellum, indicating that two kinetically distinguishable compartments exist in cerebellar tissue, which may correspond to nonspecific binding and the blood-brain barrier passing metabolite. The reference tissue models should be applied with better understanding of the biochemical nature of the radioligand and the reliability of these approaches. PMID- 22056531 TI - The future of functionally-related structural change assessment. AB - The brain is continually changing its function and structure in response to changing environmental demands. Magnetic resonance imaging (MRI) methods can be used to repeatedly scan the same individuals over time and in this way have provided powerful tools for assessing such brain change. Functional MRI has provided important insights into changes that occur with learning or recovery but this review will focus on the complementary information that can be provided by structural MRI methods. Structural methods have been powerful in indicating when and where changes occur in both gray and white matter with learning and recovery. However, the measures that we derive from structural MRI are typically ambiguous in biological terms. An important future challenge is to develop methods that will allow us to determine precisely what has changed. PMID- 22056532 TI - Bleeding risk secondary to deep vein thrombosis prophylaxis in patients with lower gastrointestinal bleeding. AB - INTRODUCTION: Deep vein thrombosis (DVT) and pulmonary embolism (PE) continue to pose a major burden on the health care system in the United States. The precise timing of anticoagulation initiation in critically ill patients with recent or active lower gastrointestinal bleeding (LGIB) is not well defined. We set out to study the safety and efficacy of early heparin administration for DVT prophylaxis in these patients. METHODS: A review of all patients admitted to the ICU with a diagnosis of LGIB over a 13-year period was performed. A total of 60 patients received subcutaneous heparin along with mechanical prophylaxis, whereas 59 patients had intermittent pneumatic compression devices alone. RESULTS: There was no difference in morbidity or mortality between the groups who received heparin and the nonheparin cohort. Neither of the groups developed a DVT or PE during the study period. Patients who received heparin had a median ICU LOS of 3 days, when compared with 2 days for patients who did not receive heparin (P < .0118). There was a significant association between units of blood received during the first 24 hours in the ICU and heparin usage (P < .0229). Those administered heparin received more units (median 3) than those who did not receive heparin (median 2). CONCLUSIONS: Administration of subcutaneous heparin increases the transfusion requirements and LOS in ICU patients with LGIB. After 24 hours, however, the blood transfusion requirements are equivalent. DVT prophylaxis in patients with a diagnosis of LGIB should be initiated after 24 hours of ICU admission. PMID- 22056533 TI - Further assessment of neuropathology in retinal explants and neuroprotection by human neural progenitor cells. AB - Explanted rat retinas show progressive photoreceptor degeneration that appears to be caspase-12-dependent. Decrease in photoreceptor density eventually affects the inner retina, particularly in the bipolar cell population. Explantation and the induced photoreceptor degeneration are accompanied by activation of Muller and microglia cells. The goal of this study was to determine whether the presence of a feeder layer of human neural progenitor cells (hNPCs) could suppress the degenerative and reactive changes in the explants. Immunohistochemical analyses showed considerable sprouting of rod photoreceptor axon terminals into the inner retina and reduced densities of cone and rod bipolar cells. Both sprouting and bipolar cell degenerations were significantly lower in retinas cultured with feeder layer cells compared to cultured controls. A tendency toward reduced microglia activation in the retinal layers was also noted in the presence of feeder layer cells. These results indicate that hNPCs or factors produced by them can limit the loss of photoreceptors and secondary injuries in the inner retina. The latter may be a consequence of disrupted synaptic arrangement. PMID- 22056534 TI - Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy. AB - PURPOSE: To assess toxicity and feasibility of reirradiation with stereotactic body radiotherapy (SBRT) after prior lung SBRT for primary lung cancer or lung metastases. PATIENTS AND MATERIALS: Twenty-nine patients reirradiated with SBRT on 32 lung lesions (11 central, 21 peripheral) were retrospectively reviewed. Median follow-up time was 12 months (range 1-97). The primary endpoint was toxicity, secondary endpoints were local control and overall survival time. Toxicity was scored according to the NCI-CTCAE version 3. RESULTS: Grade 3-4 toxicity was scored 14 times in eight patients. Three patients died because of massive bleeding (grade 5). Larger clinical target volumes (CTV) and central tumour localization were associated with more severe toxicity. There was no correlation between mean lung dose (MLD) and lung toxicity. Local control at 5 months after reirradiation was 52%, as assessed by CT-scan (n=12) or X-thorax (n=3). A larger CTV was associated with poorer local control. Kaplan-Meier estimated 1- and 2-year survival rates were 59% and 43%, respectively. CONCLUSIONS: Reirradiation with SBRT is feasible although increased risk of toxicity was reported in centrally located tumours. Further research is warranted for more accurate selection of patients suitable for reirradiation with SBRT. PMID- 22056535 TI - Outcomes of stereotactic ablative radiotherapy following a clinical diagnosis of stage I NSCLC: comparison with a contemporaneous cohort with pathologically proven disease. AB - INTRODUCTION: As a finding of benign disease is uncommon in Dutch patients undergoing surgery after a clinical diagnosis of stage I NSCLC, patients are also accepted for stereotactic ablative radiotherapy (SABR) without pathology. We studied outcomes in patients who underwent SABR after either a pathological (n=209) or clinical diagnosis (N=382). MATERIALS AND METHODS: Five hundred and ninety-one patients with a single pulmonary lesion underwent SABR after either a pathological- or a clinical diagnosis of stage I NSCLC based on a (18)FDG-PET positive lesion with CT features of malignancy. SABR was delivered to a total dose of 60Gy in 3, 5 or 8 fractions, and outcomes were compared between groups with and without pathological diagnosis. RESULTS: Patients with pathology had significantly larger tumor diameters (p<.001) and higher predicted FEV1% values (p=.025). No significant differences were observed between both groups in overall survival (p=.99) or local control (p=.98). Regional and distant recurrence rates were also similar. CONCLUSIONS: In a population with a low incidence of benign (18)FDG-PET positive lung nodules, clinical SABR outcomes were similar in large groups of patients with or without pathology. The survival benefits reported after the introduction of SABR are unlikely to be biased by inclusion of benign lesions. PMID- 22056536 TI - Is involved-field radiotherapy based on CT safe for patients with limited-stage small-cell lung cancer? AB - PURPOSE: To examine the pattern of failures in patients with limited-stage small cell lung cancer (LS-SCLC) treated with involved-field radiotherapy (IFRT) and chemotherapy, with the aim of investigating the safety of IFRT. METHODS AND MATERIALS: Two consecutive clinical phase II trials in patients with LS-SCLC conducted in our center from 1997 to 2010 were reviewed retrospectively. Both trials had the same inclusion criteria. All patients (n=108) received combined chemotherapy and thoracic radiotherapy. Only the primary tumor and involved lymphatic regions based on computed tomography (CT) scan were irradiated. Isolated nodal failure (INF) was defined as a failure in an initially uninvolved lymph node region in the absence of local recurrence or distant metastasis. RESULTS: With a median follow-up of 21 months, 78 patients experienced treatment failures. Out of 28 patients with local-regional recurrences, 16 in-field, 10 out of-field, and 2 both in-field and out-of-field recurrences were observed. INF occurred in 5 patients (4.6%), all in the ipsilateral supraclavicular area. Four patients developed simultaneously supraclavicular nodal failures and distant metastases. The median overall survival was 27 months (95% confidence interval, 24-30 months) and the median progression-free survival was 16 months (95% confidence interval, 12-21 months). For the 5 patients with INF, the median time to INF from the end of thoracic radiotherapy was 5 months (range, 1-18 months). CONCLUSIONS: IFRT based on CT scan in our patients resulted in a low rate of INF (4.6%), all in the ipsilateral supraclavicular area; but another four supraclavicular nodal failures with simultaneously distant metastases were also observed. The modern imaging with higher diagnostic capabilities of lymph node especially for supraclavicular area should be incorporated in the assessment of LS-SCLC when IFRT is being contemplated. PMID- 22056537 TI - Effects of strength training versus power training on physical performance in prefrail community-dwelling older adults. AB - BACKGROUND: It has been unclear which training mode is most effective and feasible for improving physical performance in the risk group of prefrail community-dwelling older adults. OBJECTIVE: The purpose of the present study was to compare the effects of strength training (ST) versus power training (PT) on functional performance in prefrail older adults. This study was registered at clinicaltrials.gov as NCT00783159. METHODS: 69 community-dwelling older adults (>65 years) who were prefrail according to the definition of Fried were included in a 12-week exercise program. The participants were randomized into an ST group, a PT group and a control group. All participants were supplemented with vitamin D(3) orally before entering the intervention period. The primary outcome was the global score on the Short Physical Performance Battery (SPPB). Secondary outcomes were muscle power, appendicular lean mass (aLM) measured by dual energy X-ray absorptiometry and self-reported functional deficits (Short Form of the Late-Life Function and Disability Instrument, SF-LLFDI). RESULTS: Regarding changes in the SPPB score during the intervention, significant heterogeneity between the groups was observed (p = 0.023). In pair-wise comparisons, participants in both training groups significantly (PT: p = 0.012, ST: 0.009) increased their SPPB score (PT: Delta(mean) = 0.8, ST: Delta(mean) = 1.0) compared to the control group, with no statistical difference among training groups (p = 0.301). No statistical differences were found in changes in aLM (p = 0.769), muscle power (p = 0.308) and SF-LLFDI (p = 0.623) between the groups. Muscle power significantly increased (p = 0.017) under vitamin D(3) intake. CONCLUSIONS: In prefrail community dwelling adults, PT is not superior to ST, although both training modes resulted in significant improvements in physical performance. With regard to dropout rates, ST appears to be advantageous compared to PT. The high prevalence of vitamin D(3) deficiency and the slight improvement of physical performance under vitamin D(3) supplementation among study participants underline the relevance of this approach in physical exercise interventions. PMID- 22056538 TI - Sleep disturbance interventions in oncology patients and family caregivers: a comprehensive review and meta-analysis. AB - Sleep disturbance is a significant problem for both oncology patients and family caregivers (FCs), and is associated with poorer functional status, quality of life, and potentially disease progression. This review describes a comprehensive literature search and meta-analysis of the efficacy of interventions for sleep disturbance in oncology patients and their FCs. This search revealed 47 studies that evaluated the effects of a number of interventions on sleep disturbance/sleep quality, as a primary or secondary outcome in oncology patients. The primary purposes of the review were to synthesize findings from intervention studies for sleep disturbance in oncology patients and their FCs; to evaluate the efficacy of these interventions; to identify gaps in the literature; and to provide directions for future research. In addition, all 47 intervention studies were evaluated in terms of key intervention and study characteristics. Both strong patterns and inconsistencies were identified among the studies, which complicate an evaluation of the efficacy of interventions, and may collectively guide future research. Finally, the importance of including the FC in sleep disturbance interventions is discussed. In light of the detrimental effects that sleep disturbance has on both the patient and the FC, this systematic review may better inform essential future intervention efforts. PMID- 22056539 TI - Effects of psychosocial stress on the pattern of salivary protein release. AB - Previous research suggests that acute stress can increase the release of immune relevant proteins in saliva. However, no attempts have been made to examine a wider range of salivary proteins in response to stress. In this study, we identified and quantified changes in the pattern of salivary protein release in a 45 min time period following the Trier Social Stress Test (TSST) in 12 asthmatic and 13 healthy participants. Proteins were separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis. The relative protein amounts were quantified using the Image J software (NIH), and identified and characterized using mass spectroscopy. Negative affect was increased immediately after stress in both groups. The results showed that alpha amylase, cystatin S and light chain IgA were increased after the TSST and significant increases in glutathione S transferase and prolactin inducible protein were also observed. Asthma patients showed responses similar to healthy controls, but had a tendency toward overall lower alpha amylase levels. Our findings suggest that a variety of proteins relevant to mucosal immunity are elevated following acute psychosocial stress, including glutathione S-transferase and prolactin inducible protein, which had not been characterized in this context before. PMID- 22056540 TI - Ondansetron interferes with unconditioned lying-on belly and acquisition of conditioned gaping induced by LiCl as models of nausea-induced behaviors in rats. AB - Rats selectively display conditioned gaping reactions when re-exposed to flavours previously paired with nausea-inducing treatments and drugs that reduce nausea also reduce these reactions, suggesting that they represent a model of nausea induced behavior in rats. However, these reactions rely upon learning, they are not unconditional malaise-induced reactions. Here we compared the effectiveness of the anti-nausea drug, ondansetron (OND) to interfere with the establishment of conditioned gaping reactions and the unconditional malaise-induced reaction of lying on belly (LOB). Pretreatment with OND significantly reduced both LiCl induced LOB and conditioned gaping reactions, without modifying conditioned taste avoidance. The frequency of gaping and duration of LOB were highly correlated. These results provide additional support for the validity of the conditioned gaping model as a rodent model of nausea-induced behavior. PMID- 22056541 TI - Neural interactions at the core of phonological and semantic priming of written words. AB - Word processing is often probed with experiments where a target word is primed by preceding semantically or phonologically related words. Behaviorally, priming results in faster reaction times, interpreted as increased efficiency of cognitive processing. At the neural level, priming reduces the level of neural activation, but the actual neural mechanisms that could account for the increased efficiency have remained unclear. We examined whether enhanced information transfer among functionally relevant brain areas could provide such a mechanism. Neural activity was tracked with magnetoencephalography while subjects read lists of semantically or phonologically related words. Increased priming resulted in reduced cortical activation. In contrast, coherence between brain regions was simultaneously enhanced. Furthermore, while the reduced level of activation was detected in the same area and time window (superior temporal cortex [STC] at 250 650 ms) for both phonological and semantic priming, the spatiospectral connectivity patterns appeared distinct for the 2 processes. Causal interactions further indicated a driving role for the left STC in phonological processing. Our results highlight coherence as a neural mechanism of priming and dissociate semantic and phonological processing via their distinct connectivity profiles. PMID- 22056542 TI - The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. AB - BACKGROUND: In the United States, hepatitis C virus (HCV) infection is most prevalent among adults born from 1945 through 1965, and approximately 50% to 75% of infected adults are unaware of their infection. OBJECTIVE: To estimate the cost-effectiveness of birth-cohort screening. DESIGN: Cost-effectiveness simulation. DATA SOURCES: National Health and Nutrition Examination Survey, U.S. Census, Medicare reimbursement schedule, and published sources. TARGET POPULATION: Adults born from 1945 through 1965 with 1 or more visits to a primary care provider annually. TIME HORIZON: Lifetime. PERSPECTIVE: Societal, health care. INTERVENTION: One-time antibody test of 1945-1965 birth cohort. OUTCOME MEASURES: Numbers of cases that were identified and treated and that achieved a sustained viral response; liver disease and death from HCV; medical and productivity costs; quality-adjusted life-years (QALYs); incremental cost effectiveness ratio (ICER). RESULTS OF BASE-CASE ANALYSIS: Compared with the status quo, birth-cohort screening identified 808,580 additional cases of chronic HCV infection at a screening cost of $2874 per case identified. Assuming that birth-cohort screening was followed by pegylated interferon and ribavirin (PEG IFN+R) for treated patients, screening increased QALYs by 348,800 and costs by $5.5 billion, for an ICER of $15,700 per QALY gained. Assuming that birth-cohort screening was followed by direct-acting antiviral plus PEG-IFN+R treatment for treated patients, screening increased QALYs by 532,200 and costs by $19.0 billion, for an ICER of $35,700 per QALY saved. RESULTS OF SENSITIVITY ANALYSIS: The ICER of birth-cohort screening was most sensitive to sustained viral response of antiviral therapy, the cost of therapy, the discount rate, and the QALY losses assigned to disease states. LIMITATION: Empirical data on screening and direct acting antiviral treatment in real-world clinical settings are scarce. CONCLUSION: Birth-cohort screening for HCV in primary care settings was cost effective. PRIMARY FUNDING SOURCE: Division of Viral Hepatitis, Centers for Disease Control and Prevention. PMID- 22056543 TI - The CpG island methylator phenotype in colorectal cancer: progress and problems. AB - In recent years, attention has focused on the biology and potential clinical importance of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). While it is generally well accepted that etiologically and clinically distinct subgroups exist in this disease, a precise definition of CIMP remains to be established. Here, we summarize existing literature that documents the prevalence of CIMP in CRC, with particular attention to the various methods and definitions used to classify a tumor as CIMP positive. Through a systematic review on both case-series and population based studies, we examined only original research articles reporting on sporadic CRC and/or adenomas in unselected cases. Forty-eight papers published between January 1999 and August 2011 met the inclusion criteria. We describe the use of multiple gene panels, marker threshold values, and laboratory techniques which results in a wide range in the prevalence of CIMP. Because there is no universal standard or consensus on quantifying the phenotype, establishing its true prevalence is a challenge. This bottleneck is becoming increasingly evident as molecular pathological epidemiology continues to offer possibilities for clear answers regarding environmental risk factors and disease trends. For the first time, large, unselected series of cases are available for analysis, but comparing populations and pooling data will remain a challenge unless a universal definition of CIMP and a consensus on analysis can be reached, and the primary cause of CIMP identified. PMID- 22056544 TI - Sleep deprivation and accidental fall risk in children. AB - OBJECTIVES: To look for an association between sleep deprivation and risk of accidental falls (AF) in children. METHODS: A questionnaire was applied to two groups of children aged 1-14 years, encompassing children observed in an emergency room for AF (G1) and children attending health care visits (HV) (G2). Collected data included demographic characteristics, medical history, previous week's sleep pattern (PWSP), sleep duration and sleep pattern in the preceding 24 h, mechanism of fall, and injury severity. EXCLUSION CRITERIA: acute or chronic disease or exposure to drugs interfering with sleep. Statistical analyses included Fisher's exact test, Pearson Chi-square, Fisher-Freeman-Halton test, T and Mann-Whitney tests for independent samples, and multivariate logistic regression (alpha=5%). RESULTS: We obtained 1756 questionnaires in G1 and 277 in G2. Of those, 834 in G1 and 267 in G2 were analyzed. We found an increased risk of AF in boys (OR 1.6; 95% CI 1.2-2.4). After controlling for age, gender, summer holidays, parental education and profession, lack of naps and PWSP were associated with increased risk (OR 2.1; 95% CI 1.3-3.3 and OR 2.7; 95% CI 1.2 6.1). In 3-5 year-old children there was an association between AF and a shorter than usual sleep duration in the previous 24 h (p=0.02). CONCLUSIONS: To our knowledge, our study is the largest so far to assess the association between sleep deprivation and childhood injury. It evidences a protective effect of naps in children. Sleep duration of less than 8 h increases risk of AF. Pre-schoolers may be particularly susceptible to sleep deprivation. PMID- 22056545 TI - Discriminative value of inflammatory biomarkers for suspected sepsis. AB - BACKGROUND: Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers. STUDY OBJECTIVES: To define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis. METHODS: PCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care. RESULTS: Of 336 enrolled subjects, 60% had definite infection, 13% possible infection, and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were higher in septicemia (median PCT 2.3 vs. 0.2 ng/mL; IL-6 178 vs. 72 pg/mL; CRP 106 vs. 62 mg/dL; p < 0.001). Biomarker concentrations increased with likelihood of infection and sepsis severity. Using receiver operating characteristic analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67), but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cutoff of 0.5 ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia, as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length of stay (p = 0.015), but no biomarker independently predicted discharge to a higher level of care. CONCLUSIONS: In adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequately discriminating to be used independently as diagnostic tools. PMID- 22056546 TI - Complete atrioventricular block associated with non-penetrating cardiac trauma in a 40-year-old man. AB - BACKGROUND: Myocardial contusion is a rare complication of blunt chest trauma. Transient conduction and rhythm problems, right ventricular dysfunction, or pulmonary embolism may occur after chest trauma, but these complications almost always occur early in the post-operative period. OBJECTIVES: The objective is to describe a case illustrating that trauma may induce high-grade atrioventricular block. CASE REPORT: We report the case of a patient who developed delayed onset of complete atrioventricular block after transient complete atrioventricular block and alternating bundle branch block secondary to blunt chest trauma. CONCLUSION: Even with an injury that does not seem to be caused by direct penetrating trauma to the heart, maybe every trauma patient needs an electrocardiographic evaluation. It is important to note that myocardial healing is a continuous process after trauma, and additional pathology may be revealed later in the course of healing from myocardial contusion. PMID- 22056547 TI - Traumatic uvulitis from a suction catheter. PMID- 22056548 TI - A rare cause of atrial fibrillation: mad honey intoxication. AB - BACKGROUND: Mad honey intoxication occurs after ingestion of honey containing grayanotoxin. CASE REPORT: We report the case of a 36-year-old man who ingested mad honey and developed atrial fibrillation. DISCUSSION: Mad honey intoxication is often characterized by symptoms such as hypotension, bradycardia, and syncope. Patients may also experience gastrointestinal, neurologic, and cardiovascular symptoms due to intoxication. Cardiac rhythm abnormalities, including sinus bradycardia, atrioventricular blocks, and nodal rhythms, also may be observed. To our knowledge, this is the first case report of a 36-year old man developing atrial fibrillation with a slow ventricular response after mad honey ingestion. PMID- 22056549 TI - Intravenous overdose of insulin glargine without prolonged hypoglycemic effects. AB - BACKGROUND: Insulin glargine is a long-acting insulin that can cause prolonged hypoglycemia when misdosed or overdosed subcutaneously. There are no reports of intravenous overdoses of insulin glargine. OBJECTIVES: We present a case of a patient inadvertently given a large intravenous dose of insulin glargine (100 units) who had an unremarkable course. CASE REPORT: A 46-year-old woman with a history of type 2 diabetes was found to be hyperglycemic and was mistakenly given an intravenous bolus of 100 units of insulin glargine. She did not become hypoglycemic, did not require parenteral dextrose, and her blood sugar readings stabilized within 3 h. She was admitted and observed for 17 h and discharged without complication. CONCLUSION: To our knowledge, this is the first report of a significant intravenous insulin glargine administration. This patient had an unremarkable course and recovered without any parenteral glucose. This case, along with prior studies on healthy volunteers, suggests that unlike subcutaneous overdoses, intravenous insulin glargine misdose/overdose may not need prolonged observation; an observation time of 6 h may be sufficient in these patients. PMID- 22056550 TI - Dislocation of the knee: an epidemic in waiting? AB - BACKGROUND: Knee dislocation is an uncommon but serious injury that has traditionally been associated with high velocity injuries such as motor vehicle accidents. More recently, individual cases of obese individuals sustaining knee dislocation from a low velocity mechanism have been noted. Associated injuries of knee dislocation are common and include popliteal vessel damage requiring surgical repair and injuries to the peroneal nerve. Prompt diagnosis and reduction is essential to reduce the risk of these complications. OBJECTIVES: We aim to highlight the importance of prompt diagnosis and management of obese patients presenting with knee pain after a seemingly innocuous injury who may have a knee dislocation. CASES: We present a series of four cases of dislocation of the knee that have presented to our hospital over the course of 1 year. Each was sustained by a morbidly obese female of body mass index range 35-41, age range 33-52 years, experiencing a simple mechanical fall from standing. Magnetic resonance image scanning revealed multiple knee ligament rupture in all four cases. One case had peroneal nerve palsy. CONCLUSION: This is the first series of such injuries that we are aware of and highlights a potential future increase in incidence of these major injuries as body mass in society increases, placing more strain on health care resources. Practitioners in the Emergency Department need to be aware that serious injury can be present in morbidly obese patients that have sustained no more than a fall from standing height. Prompt investigation and management is essential. PMID- 22056551 TI - Acute abdomen due to primary omental torsion: case report. AB - BACKGROUND: Primary torsion of the greater omentum is an uncommon cause of acute abdominal pain that mainly affects adults in their fourth or fifth decade. It was first described by Eitel in 1899. Since then, more than 300 cases have been reported in the published literature. Clinical presentation and imaging findings are often of limited value in the diagnosis of primary omental torsion (POT). The patients usually undergo laparotomy for "acute appendicitis" or acute abdomen of poorly defined origin. OBJECTIVES: To provide a detailed description of this rare cause of acute abdomen. CASE REPORT: We report a case of POT in a woman of reproductive age and discuss contemporary methods in diagnosis and management of the condition. CONCLUSION: Nowadays, laparoscopy is a safe and effective approach for the diagnosis and management of POT, with the advantages of reduced postoperative pain and hospital stay. Conservative management has also been advocated by some authors in selected patients with a preoperative diagnosis of POT based on computed tomography findings. PMID- 22056552 TI - Tianeptine potentiates AMPA receptors by activating CaMKII and PKA via the p38, p42/44 MAPK and JNK pathways. AB - Impairments of cellular plasticity appear to underlie the pathophysiology of major depression. Recently, elevated levels of phosphorylated AMPA receptor were implicated in the antidepressant effect of various drugs. Here, we investigated the effects of an antidepressant, Tianeptine, on synaptic function and GluA1 phosphorylation using murine hippocampal slices and in vivo single-unit recordings. Tianeptine, but not imipramine, increased AMPA receptor-mediated neuronal responses both in vitro and in vivo, in a staurosporine-sensitive manner. Paired-pulse ratio was unaltered by Tianeptine, suggesting a postsynaptic site of action. Tianeptine, 10 MUM, enhanced the GluA1-dependent initial phase of LTP, whereas 100 MUM impaired the latter phases, indicating a critical role of GluA1 subunit phosphorylation in the excitation. Tianeptine rapidly increased the phosphorylation level of Ser(831)-GluA1 and Ser(845)-GluA1. Using H-89 and KN-93, we show that the activation of both PKA and CaMKII is critical in the effect of Tianeptine on AMPA responses. Moreover, the phosphorylation states of Ser(217/221)-MEK and Thr(183)/Tyr(185)-p42MAPK were increased by Tianeptine and specific kinase blockers of the MAPK pathways (PD 98095, SB 203580 and SP600125) prevented the effects of Tianeptine. Overall these data suggest that Tianeptine potentiates several signaling cascades associated with synaptic plasticity and provide further evidence that a major mechanism of action for Tianeptine is to act as an enhancer of glutamate neurotransmission via AMPA receptors. PMID- 22056553 TI - OSA, metabolic syndrome and CPAP: effect on cardiac remodeling in subjects with abdominal obesity. AB - BACKGROUND: We evaluated whether obstructive sleep apnoea (OSA) and continuous positive airway pressure (CPAP) treatment influence left ventricular (LV) remodelling independently of abdominal obesity and metabolic syndrome (MetS). METHODS: Cardiorespiratory examination, 24-h BP monitoring and echocardiogram were performed in overweight/obese patients with increased abdominal adiposity and symptoms suggesting OSA : OSA/MetS (n.50), OSA/noMetS (n.22), noOSA/MetS (n.29), noOSA/noMets (n.16). The evaluation was repeated in 41 patients after >=18 months of CPAP. RESULTS: Despite similar age, gender, BMI and 24-h BP, the 2 groups with MetS had greater LV remodelling (LV hypertrophy and diastolic dysfunction) than the 2 groups without MetS. From multiple regression analysis independent determinants for LV mass were MetS, 24-h systolic BP and age, for LV diastolic function were LV mass index, MetS and age. After CPAP, the 20 patients with decreased body weight showed diastolic BP decrease, LV hypertrophy regression and diastolic function improvement, whereas, despite similar respiratory improvement, BP and LV parameters were unchanged in the 21 patients with body weight unchanged/increased. CONCLUSION: In patients with increased abdominal adiposity, LV remodelling is not associated to OSA per se; chronic CPAP treatment does not influence LV remodelling whose regression is mainly linked to body weight decrease. PMID- 22056554 TI - Transcriptional gene silencing of HPV16 E6/E7 induces growth inhibition via apoptosis in vitro and in vivo. AB - OBJECTIVE: Transcriptional silencing of HPV oncogenes using short interfering RNA (siRNA) blocks E6/E7 expression. Our objective was to estimate the effective value of E6/E7 specific siRNA-induced transcriptional gene silencing as a potential therapeutic strategy for cervical cancer. METHODS: In vitro studies were performed by employing two categories of siRNA targeting promoter of E6/E7 gene and E7 transcript, respectively, and inhibitory effect of both siRNAs was further observed in vitro and on xenograft in BALB/c mice that were inoculated with siRNA transfected SiHa cells and parental SiHa cells followed by siRNA intratumoral injection in vivo. Tumor volume and growth curves were assessed. Furthermore, cellular proliferation and apoptosis of inoculated tumors were determined by immunohistochemistry staining and TUNEL assay. RESULTS: The two most active siRNA sequences specifically knockdown E6/E7 expressions at mRNA level in HPV16 positive Siha cells, increased p53 and decreased p16 expressions at protein level, inhibited cell proliferation, and induced cell apoptosis in vitro. Furthermore, both siRNAs effectively inhibited tumor formation and growth no matter in mice with siRNA transfected cells in vitro or with siRNA intratumoral injection in vivo. TUNEL staining and FCM assay consistently showed that tumor retardation was through induction of cellular apoptosis. CONCLUSION: RNAi targeting the promoter of HPV16 E6/E7 acts effectively in vitro and in vivo, especially through intratumoral delivery, and may be a candidate therapeutic strategy for cervical cancer. PMID- 22056555 TI - Inhaled corticosteroid/long-acting beta2-agonist combination therapy for asthma: attitudes of specialists in Europe. AB - BACKGROUND: As new combinations of inhaled corticosteroids (ICSs) and long-acting beta(2)-agonists (LABAs) become available for the treatment of asthma, it will be important to determine criteria against which they can be evaluated. The aim of this study was to assess which attributes of combination therapy physicians consider most important. METHODS: Primary and secondary care asthma specialists (n = 32) were recruited for an expert Delphi process that was performed over three rounds to determine attributes perceived to be important in the selection of combination therapy. A pan-European survey was carried out to assess the attitudes, perceptions and prescribing behaviour of a larger population (n = 1,861) of physicians with a specialist interest in asthma treatment. RESULTS: The expert Delphi panel (response rate 59.4%) agreed that the availability of a range of doses (88% agreement in the final round), the efficacy of the combination (81%) and the safety and tolerability of the therapy (81%) were important attributes of ICS/LABA combination treatment. The potency of the ICS (69%) and the speed of onset of the LABA (69%) were also prioritized. The results of the attitudinal survey (eligibility rate 54.1%) showed that the same factors were considered important in everyday clinical practice. CONCLUSIONS: These studies identified which attributes of an ICS/LABA treatment are considered most important by an expert panel and a broader group of physicians; further research is warranted to better understand the influences that drive physician opinions. PMID- 22056556 TI - Allosteric property of the (Na++K+)-ATPase beta1 subunit. AB - (Na(+)+K(+))-ATPase (NKA) comprises two basic alpha and beta subunits: The larger alpha subunit catalyzes the hydrolysis of ATP for active transport of Na(+) and K(+) ions across the plasma membrane; the smaller beta subunit does not take part in the catalytic process of the enzyme. Little is known about allosteric regulation of the NKA beta subunit. Here, we report a surprising finding that extracellular stimuli on the native beta(1) subunit can generate a significant impact on the catalytic function of NKA. By using a beta(1) subunit-specific monoclonal antibody JY2948, we found that the JY2948-beta(1) subunit interaction markedly enhances the catalytic activity of the enzyme and increases the apparent affinity of Na(+) and K(+) ions for both ouabain-resistant rat NKA and ouabain sensitive dog NKA. This study provides the first evidence to identify an allosteric binding site residing on the NKA beta(1) subunit and uncovers the latent allosteric property of the beta(1) subunit, which remotely controls the NKA catalytic function. PMID- 22056557 TI - ABCC6 does not transport vitamin K3-glutathione conjugate from the liver: relevance to pathomechanisms of pseudoxanthoma elasticum. AB - Vitamin K is a cofactor required for gamma-glutamyl carboxylation of several proteins regulating blood clotting, bone formation and soft tissue mineralization. Vitamin K3 is an important intermediate during conversion of the dietary vitamin K1 to the most abundant vitamin K2 form. It has been suggested that ABCC6 may have a role in transporting vitamin K or its derivatives from the liver to the periphery. This activity is missing in pseudoxanthoma elasticum, a genetic disorder caused by mutations in ABCC6 characterized by abnormal soft tissue mineralization. Here we examined the efflux of the glutathione conjugate of vitamin K3 (VK3GS) from the liver in wild type and Abcc6(-/-) mice, and in transport assays in vitro. We found in liver perfusion experiments that VK3GS is secreted into the inferior vena cava, but we observed no significant difference between wild type and Abcc6(-/-) animals. We overexpressed the human ABCC6 transporter in Sf9 insect and MDCKII cells and assayed its vitamin K3-conjugate transport activity in vitro. We found no measurable transport of VK3GS by ABCC6, whereas ABCC1 transported this compound at high rate in these assays. These results show that VK3GS is not the essential metabolite transported by ABCC6 from the liver and preventing the symptoms of pseudoxanthoma elasticum. PMID- 22056558 TI - Peroxynitrite detoxification by horse heart carboxymethylated cytochrome c is allosterically modulated by cardiolipin. AB - Carboxymethylation of equine heart cytochrome c (cytc) changes its tertiary structure by disrupting the heme-Fe-Met80 distal bond, such that carboxymethylated cytc (CM-cytc) displays myoglobin-like properties. Here, the effect of cardiolipin (CL) on peroxynitrite isomerization by ferric CM-cytc (CM cytc-Fe(III)) is reported. Unlike native ferric cytc (cytc-Fe(III)), CM-cytc Fe(III) catalyzes peroxynitrite isomerization, the value of the second order rate constant (k(on)) is 6.8 * 10(4)M(-1)s(-1). However, CM-cytc-Fe(III) is less effective in peroxynitrite isomerization than CL-bound cytc-Fe(III) (CL-cytc Fe(III); k(on)=3.2 * 10(5)M(-1)s(-1)). Moreover, CL binding to CM-cytc-Fe(III) facilitates peroxynitrite isomerization (k(on)=5.3 * 10(5)M(-1)s(-1)). Furthermore, the value of the dissociation equilibrium constant for CL binding to CM-cytc-Fe(III) (K=1.8 * 10(-5)M) is lower than that reported for CL-cytc-Fe(III) complex formation (K=5.1 * 10(-5)M). Although CM-cytc-Fe(III) and CL-cytc-Fe(III) display a different heme distal geometry and heme-Fe(III) reactivity, the heme pocket and the CL cleft are allosterically linked. PMID- 22056559 TI - Functions of the Wnt/beta-catenin pathway in an anemia-induced zebrafish model of cardiomyopathy are location dependent. AB - Recent evidence that the heart is not a terminally-differentiated organ has provided more credence to investigations of pathways involved in inducing cardiomyocyte (CM) hyperplasia as a therapy for heart disease. Here, we leveraged zebrafish as a novel vertebrate model of cardiomyopathy to explore the therapeutic potential based on the Wnt/beta-catenin signaling. In the anemia induced zebrafish model of cardiomyopathy (tr265), we detected differently regulated CM hyperplasia and CM hypertrophy in the compact region and the trabecular region. To assess the effects of the Wnt/beta-catenin pathway on these two regions, the anemia line was crossed with heat shock-inducible transgenic fish to upregulate or downregulate the pathway. Upregulation resulted in increased cardiomyocyte hyperplasia in the heart and increased cardiomyocyte hypertrophy in the trabecular region, while downregulation resulted in reduced cardiomyocyte hyperplasia in the heart and reduced cardiomyocyte hypertrophy in the trabecular region. Importantly, upregulation of the pathway resulted in improved fish survival, while downregulation decreased it. In summary, our data suggested that (1) the compact region and the trabecular region respond differently during cardiac remodeling; (2) activation of the Wnt/beta-catenin pathway might exert a cardioprotective function via promoting cardiomyocyte hyperplasia. PMID- 22056560 TI - Osterix is regulated by Erk1/2 during osteoblast differentiation. AB - Osterix (Osx) is a novel zinc finger-containing transcription factor that is essential for osteoblast differentiation and bone formation in bone homeostasis. The mitogen-activated protein (MAP) kinases are a group of evolutionarily conserved proline-directed protein serine/threonine kinases that are activated in response to a variety of extracellular stimuli and mediate signal transduction from the cell surface to the nucleus. Erk1/2 plays essential roles in osteoblast differentiation and in supporting osteoclastogenesis, but the precise molecular signaling mechanisms between Osterix and Erk1/2 are not known. We therefore focused on the relationship between Osterix and Erk1/2 during osteoblast differentiation because BMP signaling induces Erk activation in osteoblasts. We investigated the role of the MAPK pathway in regulating protein levels and transcriptional functions of Osterix. We found that Erk activation by overexpression of constitutively active MEK increased the mRNA and protein levels of Osterix and enhanced the transcriptional activity of Osterix, whereas U0126, an inhibitor of MEK, suppressed the protein levels of Osterix and the transcriptional activity. Also, overexpression of constitutively active MEK stabilized Osterix protein. These results suggest that Erk1/2 regulates a major transcription factor, Osterix, during osteoblast differentiation by increasing its protein stability and transcriptional activity. PMID- 22056561 TI - Genetic ablation and chemical inhibition of IP3R1 reduce mutant huntingtin aggregation. AB - Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expansion of the polyglutamine (polyQ) stretch in huntingtin (htt). Previously, it has been shown that inhibition of the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) activity reduced aggregation of pathogenic polyQ proteins. Experimentally, this effect was achieved by modification of the intracellular IP3 levels or by application of IP3R1 inhibitors, such as 2 aminoethyl diphenylborinate (2-APB). Unfortunately, there are certain concerns about the 2-APB specificity and cytotoxicity. Moreover, a direct link between IP3R1 and polyQ aggregation has not been shown yet. In this study we show, that down-regulation of the IP3R1 levels by shRNA reduced the aggregation of mutant htt. We tested 2-APB analogs in an attempt to identify less toxic and more IP3R1 specific compounds and found that the effect of these analogs on the reduction of the mutant htt aggregation did weakly correlate with their inhibitory action toward the IP3-induced Ca(2+) release (IICR). Their effect on aggregation was not correlated with the store-operated Ca(2+) entry (SOCE), which is another target of the 2-APB related compounds. Our findings suggest that besides functional contribution of the IP3R inhibition on the mutant htt aggregation there are additional mechanisms for the anti-aggregation effect of the 2-APB related compounds. PMID- 22056562 TI - Apolipoprotein A-I stimulates cholesteryl ester transfer protein and apolipoprotein E secretion from lipid-loaded macrophages; the role of NF-kappaB and PKA signaling pathways. AB - Cholesteryl ester transfer protein (CETP) and apolipoprotein E (apoE) are secreted by macrophages. Apolipoprotein A-I (apoA-I) is a potent inducer of apoE secretion from lipid-loaded macrophages, but its effect on CETP is not known. We aimed to identify the signaling pathways involved in apoA-I and HDL-mediated regulation of CETP and apoE secretion from lipid-loaded macrophages. THP-1 macrophages were loaded with lipids by incubation with human copper-oxidized LDL. The cells were subsequently exposed to human purified apoA-I or HDL(3) with/without inhibitors of NF-kappaB (TPCK) or PKA (H89). CETP and apoE in the cultured cells and media were quantified by real-time PCR and Western blot. Results showed that in lipid-loaded macrophages: (i) CETP and apoE gene expression and secretion were increased in the presence of apoA-I, and further increased by inhibition of NF-kB with TPCK; (ii) CETP and apoE gene expression and secretion were reduced by the inhibition of PKA with H89; (iii) PKA-gamma subunit was activated by oxidized LDL and moreover by apoA-I. We also showed that: (i) siRNA-mediated CETP gene silencing diminished apoE secretion from both non-loaded and lipid-loaded macrophages; (ii) addition of apoA-I partially restored apoE secretion from lipid-loaded macrophages with the silenced CETP gene. In conclusion, our data suggest a new mechanism by which apoA-I stimulates CETP secretion, in addition to apoE, from lipid loaded macrophages, a process involving NF-kappaB inhibition and/or PKA pathway activation. PMID- 22056563 TI - A zyxin-nectin interaction facilitates zyxin localization to cell-cell adhesions. AB - Cell-cell junction remodeling is associated with dramatic actin reorganizations. Several actin regulatory systems have been implicated in actin remodeling events as cell-cell contacts are assembled and disassembled, including zyxin/LPP-VASP complexes. These complexes facilitate strong cell-cell adhesion by maintaining actin-membrane connections. It has been proposed that zyxin and LPP localize to cell-cell junctions via a well-defined interaction with alpha-actinin. This was recently confirmed for LPP, but zyxin localization at cell-cell contacts occurs independently of alpha-actinin binding. Here we seek to map the zyxin sequence responsible for localization to cell-cell contacts and identify the protein that docks zyxin at this cellular location. Previous results have shown that a zyxin fragment excluding the alpha-actin binding site and the LIM domains (amino acids 51-392) can independently localize to cell-cell contacts. Here, expression of smaller zyxin fragments show that zyxin localization requires amino acids 230 280. A yeast-two-hybrid screen, using the central region of zyxin as bait, resulted in the identification of the cell-cell adhesion receptor nectin-4 as a zyxin binding partner. Further demonstrating zyxin-nectin interactions, zyxin binds the intracellular domain of nectin-2 in vitro. Depletion of nectin-2 from L cells expressing E-cadherin results in a loss of zyxin localization to cell-cell contacts, demonstrating that the zyxin-nectin interaction plays a critical role in zyxin targeting to these sites. PMID- 22056564 TI - Cerebral gene expression and neurobehavioural responses in mice pups exposed to methylmercury and docosahexaenoic acid through the maternal diet. AB - Methylmercury (MeHg) is an environmental neurotoxicant with adverse effects particularly noted in the developing brain. The main source of MeHg exposure is seafood. However, fish is also an important source of n-3 fatty acids such as docosahexaenoic acid (DHA) which has neuroprotective effects, and which plays an important role during the prenatal development of the central nervous system. The aim of the present study was to examine the effects of DHA and MeHg individually, and in combination, on development using accumulation, behavioural and transcriptomic endpoints in a mammalian model. Analyses were performed on 15 day old mice which had been exposed to varying levels of DHA (8 or 24 mg/kg) and/or MeHg (4 mg/kg) throughout development via the maternal diet. Supplementation of the maternal diet with DHA reduced MeHg accumulation in the brain. An accelerated development of grasping reflex was seen in mice offspring in the 'MeHg+high DHA' group when compared to 'MeHg' and 'control'. Exposure to MeHg and DHA had an impact on cerebral gene expression as assessed by microarray and qPCR analysis. The results from the present study show the potential of DHA for alleviating toxicity caused by MeHg. This information may contribute towards refining risk/benefit assessment of seafood consumption and may enhance understanding of discrepancies between epidemiological studies of MeHg neurodevelopmental toxicity. PMID- 22056566 TI - Supplementation with oral vs. intravenous iron for anemia with IBD or gastrointestinal bleeding: is oral iron getting a bad rap? AB - Although iron supplementation is commonly prescribed, the amount of elemental iron needed to achieve clinical efficacy, and the optimal method of supplementation, are under debate. Use of intravenous (IV) iron replacement is increasingly being advocated. We explore the physiology of iron supplementation, review clinical data suggesting that the typical oral dosing of iron may be excessive, and compare IV and oral methods of iron supplementation with a focus on inflammatory bowel disease (IBD). Both IV and oral iron can effectively raise hemoglobin levels in iron-deficiency anemia. There is no evidence that IV iron can raise hemoglobin at a faster pace. Side effects of oral iron are probably related to the relatively high doses of elemental iron that are typically prescribed. Emerging data suggest that low-dose iron has comparable efficacy, with fewer side effects. In IBD, both oral and IV iron are effective, and there is no convincing evidence that oral iron activates or exacerbates clinical symptoms. The use of a low starting dose of oral iron, such as one ferrous sulfate tablet per day, for treatment of iron deficiency is worth considering. PMID- 22056567 TI - Increased screening colonoscopy rates and reduced racial disparities in the New York Citywide campaign: an urban model. AB - OBJECTIVES: In 2003, in response to low colonoscopy screening rates and significant sociodemographic disparities in colonoscopy screening in New York City (NYC), the NYC Department of Health and Mental Hygiene, together with the Citywide Colon Cancer Control Coalition, launched a multifaceted campaign to increase screening. We evaluated colonoscopy trends among adult New Yorkers aged 50 years and older between 2003 and 2007, the first five years of this campaign. METHODS: Data were analyzed from the NYC Community Health Survey, an annual, population-based surveillance of New Yorkers. Annual prevalence estimates of adults who reported a timely colonoscopy, one within the past 10 years, were calculated. Multivariate models were used to analyze changes over time in associations between colonoscopy screening and sociodemographic characteristics. RESULTS: Overall, from 2003 to 2007 the proportion of New Yorkers aged 50 years and older who reported timely colonoscopy screening increased from 41.7% to 61.7%. Racial/ethnic and sex disparities observed in 2003 were eliminated by 2007: prevalence of timely colonoscopy was similar among non-Hispanic whites, non Hispanic blacks, Hispanics, men, and women. However, Asians, the uninsured, and those with lower education and income continued to lag in receipt of timely colonoscopies. CONCLUSIONS: The increased screening colonoscopy rate and reduction of racial/ethnic disparities observed in NYC suggest that multifaceted, coordinated urban campaigns can improve low utilization of clinical preventive health services and reduce public-health disparities. PMID- 22056569 TI - Image of the month: Aerophagia. PMID- 22056574 TI - Non-acid reflux: the missing link between gastric atrophy and esophageal squamous cell carcinoma? AB - Esophageal cancer is the eighth most common incident cancer in the world and, due to the poor survival rate it confers, ranks sixth among all cancers in mortality. In developed countries of the western world, the incidence of esophageal squamous cell carcinoma (ESCC) has undergone a decline and adenocarcinoma now constitutes approximately half of all esophageal cancers. In these relatively low-risk areas, tobacco smoking and alcohol consumption account for ~90% of ESCC cases. Eastern countries have much higher incidences of ESCC and epidemiologic evidence would suggest that there are additional unknown causal mechanisms. Gastric atrophy has consistently been associated with ESCC, but its causal relevance has been questioned. In this issue of the American Journal of Gastroenterology, Uno et al. offer evidence that a causal link between these two entities is non-acid reflux. PMID- 22056575 TI - Gastroesophageal reflux symptoms in 9/11 survivors and workers: insights gained from tragic losses. AB - Survivors of the 2001 World Trade Center (WTC) attacks and the individuals who volunteered for the rescue and recovery efforts remain substantially burdened by psychological trauma and respiratory illnesses related to the environmental exposures. Gastroesophageal reflux symptoms (GERS) are also reported at higher rates than expected among this population. Post-traumatic stress disorder (PTSD) and exposures to the caustic aerosolized debris of the WTC are explored in further detail as potential mechanisms underlying these GERS experiences in WTC Registry participants. Recent work by Li and colleagues suggests that the WTC experience is associated with increases in GER independent of asthma and PTSD diagnoses. However, this association may be more complex since over representation of hypersensitive non-acid reflux subjects and failure to completely capture psychiatric comorbidity may also contribute to our understanding of these findings. Nonetheless, the WTC Registry offers a unique study population, and detailed psychologic profiling and physiologic testing of participants may promote greater insight into gastroesophageal reflux pathohysiology. PMID- 22056576 TI - Will H. pylori stagger under the weight of this LOAD? A novel but expensive eradication regimen. AB - In the era of increasing Helicobacter pylori resistance to clarithromycin and metronidazole used in standard treatments, newer well-tolerated regimens with high eradication success rates in practice are urgently needed. In this edition of the American Journal of Gastroenterology, a clinical trial of a novel drug combination is presented, demonstrating significantly more success in comparison with a standard "triple therapy." The new regimen (referred to as LOAD) comprises three antibiotics, levofloxaxin, doxycycline, and nitazoxanide, together with omeprazole. The LOAD regimen had around a 90% eradication rate compared with only 73% with a standard "triple therapy" regimen of amoxicillin, clarithromycin, and lansoprazole. The use of this relatively expensive novel drug combination would represent an absolute increased eradication rate of 17%, with a number needed to treat to achieve one more successful eradication of 5.88. Results from this preliminary study should prompt further evaluation of LOAD in rigorously designed clinical studies. PMID- 22056578 TI - Rifaximin therapy in minimal hepatic encephalopathy cirrhotics. PMID- 22056579 TI - Risk factors for cardiovascular events in inflammatory bowel disease. PMID- 22056581 TI - When meta-analysis misleads. PMID- 22056582 TI - Importance of rare and private NOD2 variants in foreseeing severe disease behavior in Crohn's disease. PMID- 22056584 TI - Biologics in fistulizing Crohn's disease: so near, yet so far. PMID- 22056587 TI - Endoscopic resection of a large duodenal hamartoma related to SMAD4-associated juvenile polyposis/hereditary hemorrhagic teleangiectasia syndrome. PMID- 22056588 TI - Bright times for patients with cirrhosis and delayed sleep habits: a case report on the beneficial effect of light therapy. PMID- 22056589 TI - Enterocolic lymphocytic phlebitis presenting as an intussuscepting cecal mass. PMID- 22056590 TI - Acid suppressants, fracture, and statistical adjustments for body mass index, smoking status, and calcium/vitamin D intake. PMID- 22056593 TI - Assessing bleeding risk in acute coronary syndromes. PMID- 22056594 TI - Electron- and ion-beam-induced maneuvering of nanostructures: phenomenon and applications. AB - Electron-and ion-induced bending (EIB/IIB) phenomena have been studied in self supported polycrystalline metallic and metal-amorphous bilayered nanocantilevers. The experiments reveal many interesting facts regarding electron/ion-matter interaction, which builds a proper foundation for the understanding of the phenomenon. The mechanism for bending of metallic cantilevers has been proposed to be primarily due to void-induced stress generation during ion beam irradiation. On the other hand, thermal effects have been found to play the dominant role in the case of bending of bilayer (amorphous-metal) nanocantilevers. The instantaneous, reversible, highly controllable and permanent nature of the process has been exploited to fabricate several complicated nanostructures in three dimensions. IIB of the fabricated cantilevers is shown to have a high precession mass sensing aptitude, capable of detecting a change in mass of the order of femtograms. PMID- 22056595 TI - Association of cardio-ankle vascular index with brain natriuretic peptide levels in hypertension. AB - AIMS: Plasma brain natriuteric peptide (BNP) is an established marker of cardiovascular events in individuals without heart failure. Although the cardio ankle vascular index (CAVI) is clinically used as a parameter of arterial stiffness, its usefulness for predicting cardiovascular events has not been fully examined. This study aimed to evaluate the association among CAVIs, plasma BNP levels and left ventricular (LV) hypertrophy and dysfunction in hypertensive patients. METHODS: We enrolled 136 hypertensive patients (69+/-10 years) who had been taking antihypertensive medications for at least one year. Echocardiography was performed to evaluate LV hypertrophy and function. Plasma BNP levels and CAVIs were also measured simultaneously. RESULTS: CAVI was correlated with plasma BNP (r =0.245, p =0.004). Multiple linear regression analysis revealed three independent determinants of CAVI: age (beta =0.568, p <0.001), diameter of ascending aorta (beta =0.289, p <0.001), and diabetes (beta =0.207, p =0.003). In addition, multiple linear regression analysis revealed two independent determinants of the plasma BNP level: left atrial diameter (beta =0.334, p <0.001) and CAVI (beta =0.256, p =0.002). CONCLUSION: The present study indicates that increased CAVI is independently associated with elevated plasma BNP produced by increased LV afterload, that is, arterial stiffness, in hypertensive patients. Moreover, the present study raises the possibility that CAVI may be as useful as the plasma BNP level for predicting the risk of cardiovascular events in hypertensive patients. PMID- 22056596 TI - Lipoprotein(a) complexes with beta2-glycoprotein I in patients with coronary artery disease. AB - AIM: To investigate the possible mechanisms and association of increased complexes of beta(2)-glycoprotein I with lipoprotein(a) [beta(2)-GPI-Lp(a)] levels with the presence and extent of coronary artery disease (CAD). METHODS: beta(2)-GPI-Lp(a) levels were measured in 116 patients with acute coronary syndromes (ACS), 72 patients with stable CAD and 100 control subjects. RESULTS: Compared to the control, beta(2)-GPI-Lp(a) levels (expressed after logarithmically transformation: ACS, 0.22+/-0.45 U/mL; stable CAD, 0.05+/-0.55 U/mL; control, -0.31+/-0.61 U/mL) significantly increased in both patients with ACS (p <0.001) and stable CAD (p <0.001). Univariate logistic regression analysis of risk factors revealed that the presence of beta(2)-GPI-Lp(a), ox-Lp(a) or Lp(a) was a strong risk factor for stable CAD [beta(2)GPI-Lp(a), OR 3.17, 95% CI 1.65, 6.07; ox-Lp(a), OR 2.54, 95% CI 1.33, 4.85; Lp(a), OR 3.00, 95% CI 1.56, 5.75; respectively], and especially for ACS [beta(2)-GPI-Lp(a), OR 5.38, 95% CI 2.97, 9.74; ox-Lp(a), OR 7.55, 95% CI 4.12, 13.84; Lp(a), OR 4.33, 95% CI 2.40, 7.80; respectively]. In multivariate analysis, adjusting for age, sex and plasma lipid levels, the presence of beta(2)-GPI-Lp(a) or Lp(a) was a risk factor for both stable CAD and ACS. Ox-Lp(a) was a risk factor only for ACS, while not for stable CAD. beta(2)-GPI-Lp(a) levels were found to be positively associated with Lp(a), ox-Lp(a), maximal stenosis and a number of vessel diseases in patients with ACS or stable CAD, respectively. Multiple linear regression analysis found that ox-Lp(a) and maximal stenosis accounted for 46.2% of the variation in beta(2)-GPI-Lp(a) levels. CONCLUSIONS: Elevated levels of beta(2)-GPI-Lp(a) are associated with the presence and severity of CAD, and may be a strong risk factor for atherosclerosis. PMID- 22056597 TI - Stimulation of glucose uptake and improvement of insulin resistance by aromadendrin. AB - Agents that stimulate glucose uptake and improve insulin resistance may be useful in the management of type 2 diabetes mellitus (DM). Thus, the aims of this study were to assess the effects of aromadendrin, a flavonoid from Gleditsia sinensis Lam., on stimulation of glucose uptake and improvement of insulin resistance and to characterize the molecular mechanisms underlying these activities. Insulin stimulated glucose uptake was measured in HepG2 cells and in differentiated 3T3 L1 adipocytes using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D glucose (2-NBDG), a fluorescent D-glucose analog. Expression of the peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) and adipocyte-specific fatty acid binding protein (aP2) mRNAs and the PPARgamma2 protein was analyzed in adipocytes using RT-PCR and immunoblotting, respectively. Insulin-stimulated protein kinase B (Akt/PKB) phosphorylation was measured in high glucose-induced, insulin-resistant HepG2 cells. Similar to 30 MUmol/l rosiglitazone, treatment with 30 MUmol/l aromadendrin significantly stimulated insulin-sensitive glucose uptake in both HepG2 cells and 3T3-L1 adipocytes. Aromadendrin treatment also enhanced adipogenesis and caused increases in the expression of PPARgamma2 and aP2 mRNAs and the PPARgamma2 protein in differentiated 3T3-L1 adipocytes. In high glucose-induced, insulin-resistant HepG2 cells, aromadendrin reversed the inhibition of Akt/PKB phosphorylation in response to insulin, which could be abrogated by pretreatment with LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Aromadendrin treatment induced adipogenesis by increases in PPARgamma2 expression, resulting in stimulation of glucose uptake and ameliorated insulin resistance. These findings suggest that aromadendrin may represent a potential therapeutic candidate for the management of type 2 DM. PMID- 22056598 TI - Juvenile and adult rats differ in cocaine reward and expression of zif268 in the forebrain. AB - Adolescents are more likely to experiment with and become addicted to drugs of abuse. A number of studies indicate that the developmental forebrain may be responsible for making adolescents vulnerable to the addictive properties of such drugs. The aim of this study was to first compare behavioral responses to novelty and cocaine between juvenile and adult rats and then compare levels of the immediate-early gene zif268 activation in several forebrain areas via in situ hybridization. We found that juveniles demonstrated higher locomotion scores and required a higher dose of cocaine than adults to establish a conditioned place preference. Additionally, at this higher dose, juvenile rats exhibited higher levels of zif268 mRNA in the prefrontal cortex compared with adults. A developmental effect for increased zif268 mRNA was also observed in the striatum and nucleus accumbens, but there was no interaction with the cocaine dose. These findings hold interesting implications for the study of the molecular mechanisms underlying juvenile drug addiction. PMID- 22056599 TI - Brain-derived neurotrophic factor promotes adaptive plasticity within the spinal cord and mediates the beneficial effects of controllable stimulation. AB - Brain-derived neurotrophic factor (BDNF) has been characterized as a potent modulator of neural plasticity in both the brain and spinal cord. The present experiments use an in vivo model system to demonstrate that training with controllable stimulation increases spinal BDNF expression and engages a BDNF dependent process that promotes adaptive plasticity. Spinally transected rats administered legshock whenever one hind limb is extended (controllable stimulation) exhibit a progressive increase in flexion duration. This simple form of response-outcome (instrumental) learning is not observed when shock is given independent of leg position (uncontrollable stimulation). Uncontrollable electrical stimulation also induces a lasting effect that impairs learning for up to 48 h. Training with controllable shock can counter the adverse consequences of uncontrollable stimulation, to both prevent and reverse the learning deficit. Here it is shown that the protective and restorative effect of instrumental training depends on BDNF. Cellular assays showed that controllable stimulation increased BDNF mRNA expression and protein within the lumbar spinal cord. These changes were associated with an increase in the BDNF receptor TrkB protein within the dorsal horn. Evidence is then presented that these changes play a functional role in vivo. Application of a BDNF inhibitor (TrkB-IgG) blocked the protective effect of instrumental training. Direct (intrathecal) application of BDNF substituted for instrumental training to block both the induction and expression of the learning deficit. Uncontrollable stimulation also induced an increase in mechanical reactivity (allodynia), and this too was prevented by BDNF. TrkB-IgG blocked the restorative effect of instrumental training and intrathecal BDNF substituted for training to reverse the deficit. Taken together, these findings outline a critical role for BDNF in mediating the beneficial effects of controllable stimulation on spinal plasticity. PMID- 22056601 TI - Sex differences in the expression of serotonin-synthesizing enzymes in mouse trigeminal ganglia. AB - Migraine headaches are more prevalent in women and often occur during the early phases of the menstrual cycle, implying a link between migraine and ovarian steroids. Serotonin (5-HT) and its receptors have been proposed to play a key role in the pathophysiology of migraine. The trigeminal ganglion (TG) has been proposed as a site for 5-HT synthesis based on the expression of the rate limiting enzyme in peripheral 5-HT synthesis, tryptophan hydroxylase 1 (TPH1), in female rodent trigeminal ganglia. Tryptophan hydroxylase levels vary over the estrus cycle, however, the expression and potential regulation of other enzymes involved in 5-HT synthesis has not been reported in this tissue. C57/BL6 mice of both sexes expressed TPH1 and aromatic amino acid decarboxylase (AADC), the key enzymes involved in 5-HT synthesis. Levels of both enzymes were significantly higher in juvenile males compared with females. In naturally cycling females TPH1 and AADC expression was highest during proestrus when compared with the other phases of the cycle, and this regulation was mirrored at the mRNA level. In situ hybridization experiments detected TPH1 and AADC mRNA in presumptive neurons in the trigeminal ganglion. Both key enzymes involved in the synthesis of 5-HT are expressed in mouse trigeminal ganglion and are localized to neurons. The levels of these enzymes are dependent on gender and estrus cycle stage, suggesting that ovarian steroids might play a role in the regulation of sensory neuron 5-HT synthesis. PMID- 22056600 TI - Spinal matrix metalloproteinase 3 mediates inflammatory hyperalgesia via a tumor necrosis factor-dependent mechanism. AB - Matrix metalloproteinases (MMPs) have been implicated in the modulation of synaptic plasticity, glial activation, and long-term potentiation in the CNS. Here we demonstrate for the first time a mechanism for the regulation of nociceptive processing by spinal MMP-3 during peripheral inflammation. We first determined by western blotting that the catalytic (active) form of MMP-3 (cMMP-3) is increased in lumbar spinal cord following peripheral inflammation in rats. The peripheral inflammation-induced thermal hyperalgesia and tactile hypersensitivity was transiently (2-3 h) attenuated by intrathecal (IT) pretreatment with either an MMP-3 inhibitor (NNGH), or a broad spectrum MMP inhibitor (GM6001). In addition, IT delivery of cMMP-3 evoked hypersensitivity, whereas the pro (enzymatically inactive) form of MMP-3 did not. This suggests a pro-algesic effect of spinal MMP-3 mediated by an enzymatic mechanism. This cMMP-3-induced hypersensitivity is concurrent with increased tumor necrosis factor (TNF) in the spinal cord. The hypersensitivity behavior is prevented by intrathecal etanercept (TNF blockade). Treatment with cMMP-3 resulted in an increase in TNF release from spinal primary microglial, but not astrocyte cultures. These findings thus present direct evidence implicating MMP-3 in the coordination of spinal nociceptive processing via a spinal TNF-dependent mechanism. PMID- 22056602 TI - Dynamic modeling of alpha-synuclein aggregation in dopaminergic neuronal system indicates points of neuroprotective intervention: experimental validation with implications for Parkinson's therapy. AB - Protein aggregation is the major pathological hallmark seen in neurodegenerative disorders such as Parkinson's disease (PD). Alpha-synuclein (alphaS) is the main component of protein aggregates that form Lewy bodies (LBs) in PD and dementia with LBs. There have been several attempts to intervene in the process of expression, modification, clearance, and aggregation of alphaS as a therapeutic strategy toward neuroprotection. In this study, we have employed a novel, predictive, system level approach in silico to study four different strategies of anti-aggregation therapies: (a) reduction in alphaS modifications such as phosphorylation, nitration, or truncation in an approach called "seed clearance;" (b) "anti-oligomerization" approach through blocking the early oligomers formation; (c) "oligomers clearance" process by increasing its lysosomal degradation; and (d) "anti-aggregation" that involves prevention of aggregate formation at a later stage. These strategies were tested in a virtual dopaminergic neuronal system triggered by overexpression (OE) of mutant alphaS A53T with or without rotenone (Rot)-induced oxidative stress. The results were compared by analyzing markers related to various end points such as oxidative stress, dopamine (DA) metabolism, proteasome function, survival and apoptosis. The experimental system and anti-oligomerization strategies were recapitulated in vitro in M17 dopaminergic cells overexpressing mutant alphaS-A53T triggered with Cu(II)-mediated oxidative stress, and the experimental data prospectively corroborated with the predictive results. Through this analysis, we found that intervention in the early part of the aggregation pathway by prevention of oligomer formation and increased clearance is indeed a good neuroprotective strategy, whereas anti-aggregation efforts to break up the aggregate at later stages has negative effects on the system. PMID- 22056603 TI - Potential autophagy enhancers attenuate rotenone-induced toxicity in SH-SY5Y. AB - Recent studies have shown that autophagy upregulation may be a tractable therapeutic intervention for clearing the disease-causing proteins, including alpha-synuclein, ubiquitin, and other misfolded or aggregated proteins in Parkinson's disease (PD). In this study, we explored a novel pharmacotherapeutic approach to treating PD by utilizing potential autophagy enhancers valproic acid (VPA) and carbamazepine (CBZ). Pretreatment with VPA (3 mM) and CBZ (50 MUM) along with positive control rapamycin (Rap, 0.2 MUM) or lithium (LiCl, 10 mM) significantly enhanced cell viability, decreased rotenone-induced nuclear fragmentation and apoptosis, ameliorated the decrease in mitochondrial membrane potential, reduced reactive oxygen species generation in the human neuroblastoma SH-SY5Y cells. Specifically, the numbers of lysosomes and autophagic vacuolar organelles were increased and the microtubule-associated protein 1 light chain 3 II (LC3-II) expression was up-regulated by VPA, CBZ, Rap, and LiCl (53%, 31%, 72%, and 63%), suggesting that these agents activated autophagic pathways. Moreover, pretreatment with the autophagy inhibitor chloroquine (Chl, 10 MUM) remarkably strengthened rotenone toxicity in these cells. Our results suggest that VPA and CBZ, the most commonly used anti-epilepsy and mood-stabilizing medications with low-risk and easy administration might be potential therapeutics for PD. PMID- 22056604 TI - Molecular and morphological evidences place the extinct New Zealand endemic Turnagra capensis in the Oriolidae. AB - The affinities of Piopio Turnagra capensis, an extinct New Zealand passerine, remain poorly known. It has been included into or associated with several bird families (Calleatidae, Cracticidae, Pachycephalidae, Ptilonorhynchidae, Turdidae), often on tenuous grounds. We reassessed Turnagra phylogenetic relationships using nuclear and mitochondrial sequences and a set of morphological and behavioural traits. Molecular and phenotypic characters strongly suggest a novel hypothesis, congruently placing Turnagra in Oriolidae, a highly dispersive corvoid family distributed from the Austro-Papuan landmass to Eurasia and Africa, but missing from the Pacific islands. We show also that the published molecular support to link Turnagra with Ptilonorhynchidae was biased by the use of incorrect genetic data and weak analyses. PMID- 22056605 TI - Invasion of protein coding genes by green algal ribosomal group I introns. AB - The spread of group I introns depends on their association with intron-encoded homing endonucleases. Introns that encode functional homing endonuclease genes (HEGs) are highly invasive, whereas introns that only encode the group I ribozyme responsible for self-splicing are generally stably inherited (i.e., vertical inheritance). A number of recent case studies have provided new knowledge on the evolution of group I introns, however, there are still large gaps in understanding of their distribution on the tree of life, and how they have spread into new hosts and genic sites. During a larger phylogenetic survey of chlorophyceaen green algae, we found that 23 isolates contain at least one group I intron in the rbcL chloroplast gene. Structural analyses show that the introns belong to one of two intron lineages, group IA2 intron-HEG (GIY-YIG family) elements inserted after position 462 in the rbcL gene, and group IA1 introns inserted after position 699. The latter intron type sometimes encodes HNH homing endonucleases. The distribution of introns was analyzed on an exon phylogeny and patterns were recovered that are consistent with vertical inheritance and possible horizontal transfer. The rbcL 462 introns are thus far reported only within the Volvocales, Hydrodictyaceae and Bracteacoccus, and closely related isolates of algae differ in the presence of rbcL introns. Phylogenetic analysis of the intron conserved regions indicates that the rbcL699 and rbcL462 introns have distinct evolutionary origins. The rbcL699 introns were likely derived from ribosomal RNA L2449 introns, whereas the rbcL462 introns form a close relationship with psbA introns. PMID- 22056606 TI - Comments on: "A simple method for preventing pharyngocutaneous fistula after pharyngolaryngectomy using a mesenteric turnover flap". PMID- 22056607 TI - Development of an anhydrotetracycline-inducible gene expression system for solvent-producing Clostridium acetobutylicum: A useful tool for strain engineering. AB - Clostridium acetobutylicum is an important solvent (acetone-butanol-ethanol) producing bacterium. However, a stringent, effective, and convenient-to-use inducible gene expression system that can be used for regulating the gene expression strength in C. acetobutylicum is currently not available. Here, we report an anhydrotetracycline-inducible gene expression system for solvent producing bacterium C. acetobutylicum. This system consists of a functional chloramphenicol acetyltransferase gene promoter containing tet operators (tetO), Pthl promoter (thiolase gene promoter from C. acetobutylicum) controlling TetR repressor expression cassette, and the chemical inducer anhydrotetracycline (aTc). The optimized system, designated as pGusA2-2tetO1, allows gene regulation in an inducer aTc concentration-dependent way, with an inducibility of over two orders of magnitude. The stringency of TetR repression supports the introduction of the genes encoding counterselective marker into C. acetobutylicum, which can be used to increase the mutant screening efficiency. This aTc-inducible gene expression system will thus increase the genetic manipulation capability for engineering C. acetobutylicum. PMID- 22056608 TI - Effects of oral loperamide on efficacy of naltrexone, baclofen and AM-251 in blocking ethanol self-administration in rats. AB - Naltrexone is a MU-opioid receptor antagonist that has been extensively studied for its ability to block the rewarding effects of ethanol. Opioid receptors are widely distributed within the gastrointestinal tract (GIT). Typically, naltrexone is administered by parenteral routes in nonclinical studies. We initially tested if opioid receptors within the GIT would influence the ability of oral naltrexone to inhibit ethanol oral self-administration in rats using the co-administration of oral loperamide, a peripherally restricted opioid agonist. As expected, oral naltrexone only had modest effects on ethanol intake, and the response was not dose-dependent. However in rats, treatment with loperamide prior to the administration of naltrexone resulted in a suppression of ethanol intake which approached that observed with naltrexone given by the subcutaneous (SC) route. Importantly, administration of loperamide prior to administration of naltrexone did not alter blood concentrations of naltrexone. We then evaluated if oral loperamide would enhance effects of baclofen (a GABA(B) receptor agonist) and AM 251 (a CB-1 receptor antagonist) and found that pre-treatment with loperamide did potentiate the action of both drugs to reduce ethanol self-administration. Finally, the specific opioid receptor type involved was investigated using selective MU- and kappa-receptor antagonists to determine if these would affect the ability of the AM-251 and loperamide combination to block ethanol drinking behavior. The effect of loperamide was blocked by ALKS 37, a peripherally restricted MU-receptor antagonist. These data suggest an important role for opioid receptors within the GIT in modulating central reward pathways and may provide new insights into strategies for treating reward disorders, including drug dependency. PMID- 22056609 TI - Natural course and comorbidities of allergic and nonallergic rhinitis in children. AB - BACKGROUND: Not much data are available from large, unselected, birth cohort studies on the natural course and comorbidities of rhinitis in children. OBJECTIVE: To study phenotypes of rhinitis in relation to the natural course and comorbidities of allergic diseases in preschool-age and early school-age children. METHODS: We analyzed data from a birth cohort of 2024 children, for whom information on IgEs against 8 common inhaled allergens was available, collected at age 4 and 8 years. The children were assigned to groups of allergic rhinitis (rhinitis with sensitization to allergens), nonallergic rhinitis (rhinitis without sensitization), allergic sensitization but no rhinitis, or neither rhinitis nor sensitization. RESULTS: The proportion of children with allergic rhinitis increased from 5% to 14% from age 4 to 8 years, whereas the proportion of children with nonallergic rhinitis decreased slightly over the same period of development, from 8% to 6%. Of the children with allergic rhinitis when they were 4 years old, 12% underwent remission by the time they were 8 years old; of the children with nonallergic rhinitis, 73% underwent remission during this period of development. Among 4-year-olds without rhinitis who were sensitized to allergen, 56% had allergic rhinitis when they were 8 years old. Among 4- and 8 year-olds, allergic rhinitis and nonallergic rhinitis were associated with asthma, eczema, and food hypersensitivity. Twenty-five percent of 8-year-olds with allergic rhinitis also had oral allergy syndrome. CONCLUSIONS: Fewer preschool-age children with allergic rhinitis undergo remission than do those with nonallergic rhinitis. Sensitization to inhaled allergens at an early age (4 years) precedes the development of allergic rhinitis, whereas symptoms of rhinitis do not. Oral allergy syndrome is common among 8-year-olds with allergic rhinitis. PMID- 22056610 TI - The designer aminoglycoside NB84 significantly reduces glycosaminoglycan accumulation associated with MPS I-H in the Idua-W392X mouse. AB - Suppression therapy utilizes compounds that suppress translation termination at in-frame premature termination codons (PTCs) to restore full-length, functional protein. This approach may provide a treatment for diseases caused by nonsense mutations such as mucopolysaccharidosis type I-Hurler (MPS I-H). MPS I-H is a lysosomal storage disease caused by severe alpha-L-iduronidase deficiency and subsequent lysosomal glycosaminoglycan (GAG) accumulation. MPS I-H represents a good target for suppression therapy because the majority of MPS I-H patients carry nonsense mutations, and restoration of even a small amount of functional alpha-L-iduronidase may attenuate the MPS I-H phenotype. In this study, we investigated the efficiency of suppression therapy agents to suppress the Idua W392X nonsense mutation in an MPS I-H mouse model. The drugs tested included the conventional aminoglycosides gentamicin, G418, amikacin, and paromomycin. In addition, the designer aminoglycosides NB54 and NB84, two compounds previously designed to mediate efficient PTC suppression with reduced toxicity, were also examined. Overall, NB84 suppressed the Idua-W392X nonsense mutation much more efficiently than any of the other compounds tested. NB84 treatment restored enough functional alpha-L-iduronidase activity to partially reverse abnormal GAG accumulation and lysosomal abundance in mouse embryonic fibroblasts derived from the Idua-W392X mouse. Finally, in vivo administration of NB84 to Idua-W392X mice significantly reduced urine GAG excretion and tissue GAG storage. Together, these results suggest that NB84-mediated suppression therapy has the potential to attenuate the MPS I-H disease phenotype. PMID- 22056611 TI - L-shaped right-to-left crossed-fused renal ectopia with left dysplastic ureter. AB - Crossed-fused renal ectopia is a relatively rare congenital malformation. Herein, we report a case of L-shaped right- to-left crossed-fused renal ectopia with a left dysplastic ureter in a 5-year-old girl. She underwent a left nephrectomy and the postoperative course was uneventful. PMID- 22056612 TI - Changes in bone turnover markers during the close season in elite football (soccer) players. AB - OBJECTIVES: Bone turnover marker changes in response to physical activity are well documented. There is, however, little information on the extent and severity of skeletal de-conditioning in athletes in response to rest periods. This study analyses changes in markers of bone resorption and bone formation during the close season within the squad of an English Football Association Championship club. DESIGN: Evaluation was performed on the first team football squad just before the end of the 2007/2008 football season and again 8 weeks later before pre-season testing and training. METHOD: Bone resorption was measured by serum concentration of C-terminal telopeptide (CTx) and bone formation by serum concentration of the N-terminal propeptide of type I procollagen (PINP). Twenty football players aged from 18 to 36 years (mean 23.6 years) were included in the study. RESULTS: The mean change in CTx during the close season was +0.14 ng/ml (95% CI: 0.21 to 0.06, p=0.001). The mean change in PINP was -10.8 ng/ml (95% CI: -3.9 to -17.7, p=0.004). CONCLUSIONS: In professional football players, a close season rest of 8 weeks results in an increase in bone resorption and a decrease in bone formation markers. This imbalance between formation and resorption may have negative effects on bone mass and structure. Future research should focus on understanding the many factors that could contribute to the changes found in the study during the close season. PMID- 22056613 TI - Recognition of methylated histones: new twists and variations. AB - Histone tails undergo methylation at their lysines and arginines. These chemical marks act as traffic signals that direct activity of chromatin remodeling complexes to appropriate regions of the genome. A surprisingly diverse group of effector protein modules in chromatin remodeling complexes and their associated factors are involved in the recognition of histone methyllysines. Previous studies generally painted a picture of individual lysines recognized by these protein modules in a 1:1 fashion. However, recent structural studies show more complex interactions where the critical lysines are recognized in pairs, or in the context of nucleosomal DNA, or within the central pore of repeat motifs. These interactions extend our understanding of how histone tail recognition can be enhanced through coupled interactions within a single module or through the cooperation of two different molecules. PMID- 22056614 TI - The CWD allele catalog in China. PMID- 22056615 TI - Diagnosis of immediate hypersensitivity to beta-lactam antibiotics can be made safely with current approaches. AB - BACKGROUND: Diagnosing immediate hypersensitivity to beta-lactam antibiotics is still a significant problem. Recently, a new penicillin testing reagent was introduced to the market. In this study, the recommendations of the European Network of Drug Allergy (ENDA) for the diagnosis of immediate reactions to beta lactams were followed, and the negative predictive value of this approach with currently available reagents was assessed. METHODS: Eighty patients (age range: 6 74 years) with a history of immediate reactions to beta-lactams were included. All cases underwent skin testing with benzylpenicilloyl-polylysine (PPL) and minor determinant mixture (MDM), followed by the culprit drug if necessary. If this step was negative, a drug provocation test was offered. If this step also yielded a negative result, then the patients were recommended to use beta-lactam antibiotics in future whenever their use was indicated. RESULTS: Overall, 29 patients (36.2%) were diagnosed as beta-lactam allergic. The majority of the cases (72.4%) were diagnosed by positive skin tests to either PPL or MDM, whereas 10.3% were diagnosed by skin testing with culprit drugs and 17.2% with drug provocation tests. Regarding the use of the tested drug in the long term, almost half of the contacted patients had had an indication to use the tested drug and the majority had taken the whole course without problems. CONCLUSIONS: Although currently available new penicillin tests provide sufficient allergy data, all the steps recommended by ENDA should be followed in the diagnosis of immediate reactions to beta-lactams. If these steps are negative, the patients usually tolerate beta-lactams and only a few develop mild, non-life-threatening reactions in the long term. PMID- 22056616 TI - The novel ATP-sensitive potassium channel opener iptakalim prevents insulin resistance associated with hypertension via restoring endothelial function. AB - AIM: To investigate the effects of iptakalim on endothelial dysfunction induced by insulin resistance (IR) and to determine whether iptakalim improved IR associated with hypertension in fructose-fed rats (FFRs) and spontaneously hypertensive rats (SHRs). METHODS: Human umbilical vein endothelial cells (HUVECs) were used for in vitro study. The levels of endothelial vasoactive mediators and eNOS protein expression were determined using radioimmunoassays, ELISAs, colorimetric assays or Western blotting. Sprague-Dawley rats were fed with a high-fructose diet. In both FFRs and SHRs, tail-cuff method was used to measure systolic blood pressure (SBP), and hyperinsulinemic- euglycemic clamp was used to evaluate IR states. RESULTS: (1) Cultured HUVECs incubated with the PI3 kinase inhibitor wortmannin (50 nmol/L) and insulin (100 nmol/L) induced endothelial dysfunction characterized by significantly reduced release of NO and expression of eNOS protein, and significantly increased production of ET-1. Pretreatment with iptakalim (0.1-10 MUmol/L) could prevent the endothelial dysfunction. (2) In FFRs, the levels of SBP, fasting plasma glucose and insulin were significantly elevated, whereas the glucose infusion rate (GIR) and insulin sensitive index (ISI) were significantly decreased, and the endothelium-dependent vascular relaxation response to ACh was impaired. These changes could be prevented by oral administration of iptakalim (1, 3, or 9 mg.kg(-1).d(-1), for 4 weeks). The imbalance between serum NO and ET-1 was also ameliorated by iptakalim. (3) In 2-4 month-old SHRs (IR was established at the age of 4 months), oral administration of iptakalim (1, 3, or 9 mg.kg(-1).d(-1), for 8 weeks) significantly ameliorated hypertension and increased the GIR to the normal level. CONCLUSION: These results demonstrate that iptakalim could protect against IR induced endothelial dysfunction, and ameliorate IR associated with hypertension, possibly via restoring the balance between NO and ET-1 signaling. PMID- 22056617 TI - Beneficial effects of mood stabilizers lithium, valproate and lamotrigine in experimental stroke models. AB - The mood stabilizers lithium, valproate and lamotrigine are traditionally used to treat bipolar disorder. However, accumulating evidence suggests that these drugs have broad neuroprotective properties and may therefore be promising therapeutic agents for the treatment of neurodegenerative diseases, including stroke. Lithium, valproate and lamotrigine exert protective effects in diverse experimental stroke models by acting on their respective primary targets, ie, glycogen synthase kinase-3, histone deacetylases and voltage-gated sodium channels, respectively. This article reviews the most recent findings regarding the underlying mechanisms of these phenomena, which will pave the way for clinical investigations that use mood stabilizers to treat stroke. We also propose several future research avenues that may extend our understanding of the benefits of lithium, valproate and lamotrigine in improving stroke outcomes. PMID- 22056618 TI - Systolic blood pressure below 110 mmHg is associated with increased mortality in penetrating major trauma patients: Multicentre cohort study. AB - INTRODUCTION: Non-invasive systolic blood pressure (SBP) measurement is a commonly used triaging tool for trauma patients. A SBP of <90mmHg has represented the threshold for hypotension for many years, but recent studies have suggested redefining hypotension at lower levels. We therefore examined the association between SBP and mortality in penetrating trauma patients. METHODS: We conducted a prospective cohort study in adult (>=16 years) penetrating trauma patients. Patients were admitted to hospitals belonging to the Trauma Audit and Research Network (TARN) between 2000 and 2009. The main outcome measure was the association between SBP and mortality at 30 days. Multivariate logistic regression models adjusted for the influence of age, gender, Injury Severity Score (ISS) and Glasgow Coma Score (GCS) on mortality were used. RESULTS: 3444 patients with a median age of 30 years (IQR 22.5-41.4), SBP of 126mmHg (IQR 107 142), ISS of 9 (IQR 9-14) and GCS of 15 (IQR 15-15), were analysed. Multivariable logistic regression analysis adjusted for age, gender, severity of injury and level of consciousness showed a cut-off for SBP at <110mmHg, after which increased mortality was observed. Compared with the reference group with SBP 110 129mmHg, mortality was doubled at SBP 90-109mmHg, was four-fold higher at 70 89mmHg and 10-fold higher at <70mmHg. SBP values >=150mmHg were associated with decreased mortality. CONCLUSION: We recommend that penetrating trauma patients with a SBP<110mmHg are triaged to resuscitation areas within dedicated, appropriately specialised, high-level care trauma centres. PMID- 22056619 TI - Training teams and leaders to reduce resuscitation errors and improve patient outcome. PMID- 22056620 TI - N,N'-dicyclohexylsulfamide and N,N'-diphenethylsulfamide are anticonvulsant sulfamides with affinity for the benzodiazepine binding site of the GABA(A) receptor and anxiolytic activity in mice. AB - A set of sulfamides designed, synthesized and evaluated against maximal electroshock seizure (MES) and pentilenetetrazol (PTZ) tests with promising results, were tested for their affinity for the benzodiazepine binding site of the GABA(A) receptor. The most active compounds, N,N'-dicyclohexylsulfamide (7) and N,N'-diphenethylsulfamide (10), competitively inhibited the binding of [(3)H] flunitrazepam to the benzodiazepine binding site with K(i)+/-SEM values of 27.7+/ 4.5MUM (n=3) and 6.0+/-1.2MUM (n=3), respectively. The behavioral actions of these sulfamides, i.p. administered in mice, were examined in the plus-maze, hole board and locomotor activity assays. Compound 7 exhibited anxiolytic-like effects in mice evidenced by a significant increase of the parameters measured in the hole-board test (at 1 and 3mg/kg) and the plus-maze assay (at 1 and 3mg/kg). Compound 10 evidenced anxiolytic activity in the plus-maze and the hole-board tests at 1mg/kg. Locomotor activity of mice was not modified by compound 7 or 10 at the doses tested. Flumazenil, a non selective benzodiazepine binding site antagonist, was able to completely reverse the anxiolytic-like effects of these sulfamides, proving that the GABA(A) receptor is implicated in this action. Anxiety represents a major problem for people with epilepsy. The use of anxiolytic and anticonvulsant sulfamides would be beneficial to individuals who suffer from both disorders. PMID- 22056621 TI - Inhibition of genotoxic stress induced apoptosis by novel TAT-fused peptides targeting PIDDosome. AB - Genotoxic stress induced apoptosis is mediated by the formation of PIDDosome, which is a caspase-2 activating complex composed of three protein components, PIDD, RAIDD, and caspase-2. Here, synthetic TAT-fused peptides designed by the structure of PIDD and RAIDD, TAT-Y814A and TAT-R147E, respectively, were produced and tested for their ability to inhibit PIDDosome formation in vitro as well as to attenuate genotoxic stress-induced apoptosis in human renal cancer cells. The results show that TAT-Y814A and TAT-R147E have the potential to inhibit formation of the PIDDosome in a dose-dependent manner. Furthermore, both peptides partially inhibit genotoxic stress mediated apoptosis and activation of caspase2 and caspase3 in Caki cells. These results suggest that TAT-Y814A (also TAT-R147E) is a novel inhibitor of genotoxic stress-induced apoptosis that may serve as a prototype for anti-apoptotic drug development. PMID- 22056622 TI - Kindlin-2: a novel adhesion protein related to tumor invasion, lymph node metastasis, and patient outcome in gastric cancer. AB - BACKGROUND: Kindlin-2 has been confirmed as an essential element of bidirectional integrin signaling. In recent years, the relationship between Kindlin-2 expression and cancers has been a focus of interest. However, the relationship between Kindlin-2 expression in gastric cancer and tumor invasion, metastasis, and the outcome of patients have not been studied. METHODS: Kindlin-2 expression at protein and RNA levels were detected by Western blot and real-time polymerase chain reaction in 40 pairs of gastric cancer samples. In addition, the correlations between Kindlin-2 expression and clinicopathologic factors as well as the prognosis of the patients were analyzed. Multivariate Cox regression was used to study the effect of Kindlin-2 expression on overall and progression-free survival. RESULTS: We found that Kindlin-2 was up-regulated both at RNA (P = .027) and protein levels (P = .014) in gastric cancer tissues. Tumor samples with high Kindlin-2 expression (Kindlin-2/beta-actin:tumor tissue/paraneoplastic tissue, >=2) was observed in 55% of the patients. Moreover, Kindlin-2 expression had a significant positive correlation with tumor stromal invasion (P = .014), lymph node metastasis (P = .007), and TNM stage (P = .014). Patients with high Kindlin-2 expression had significantly poorer overall survival (P = .012) and progression-free survival (P = .012). High Kindlin-2 expression was an independent risk factor of progression-free survival (hazard ratio, 5.2; 95% confidence interval, 1.1-3.3; P = .032). CONCLUSIONS: Kindlin-2 may play an important role in the development of gastric cancer and it is a potential factor that could be used to evaluate the outcome of gastric cancer. Kindlin-2 may shed new light on evaluating the prognosis and targeted therapy of gastric cancer. PMID- 22056623 TI - Locomotor response to novelty correlates with the number of midbrain tyrosine hydroxylase positive cells in rats. AB - The present study investigated whether the higher dopaminergic system activation in rats with high (HRs) rather than low (LRs) locomotor activity in response to novelty depend on the number of cells containing the enzyme tyrosine hydroxylase (TH(+)) and/or differences in the morphology of these cells. One week after the novelty test, brains from male Wistar rats (HRs and LRs) were collected and stained for TH expression (immunohistochemistry) and for morphological analysis (immunofluorescent staining). The morphology and total number of TH(+) cells was analyzed for each A9 (substantia nigra) and A10 (ventral tegmental area) group of the midbrain dopaminergic cells. We found that HRs had a higher total number of TH(+) cells in the whole midbrain dopaminergic region (A9-A10) and in the A9 group only than LRs. In particular midbrain dopaminergic groups of neurons, HR/LR differences were regionally specific: HRs had a higher total number of TH(+) cells in the A9, and in the anterior part of the A10. In contrast, the LRs had a higher number of TH(+) cells in the parabrachial pigmented nucleus (A10) and in the posterior part of the A9. There were no significant differences in the morphology of the midbrain dopamine neurons between HRs and LRs. Moreover, there was a positive correlation between the total number of TH(+) neurons and the locomotor activity score in response to novelty in the whole A9-A10 region and in the particular A9 group only. The results obtained indicate that the higher behavioral activation in resting conditions correlates with the higher number rather than changes in the morphology of the midbrain dopaminergic TH(+) cells. It supports findings on the higher level of dopaminergic system activation in high responders to novelty that depends on the number of midbrain dopaminergic TH(+) neurons. PMID- 22056624 TI - Acidification of grape marc for alcoholic beverage production: effects on indigenous microflora and aroma profile after distillation. AB - Grappa is an Italian alcoholic beverage obtained from distillation of grape marc, the raw material derived from separation of must during the winemaking process. Marc is stored for a period lasting from few days to several weeks, when fermentation of residual sugars occurs mainly by yeast activity. Many distilleries have adopted different solutions to manage this critical phase in order to avoid spoilage microorganisms: marc acidification is the most widely diffused. In this work, Prosecco grape pomace was acidified with sulphuric acid (to pH 2.9) and stored, whereas non-acidified grape marc was used as control (pH 3.9). Samples for microbiological analysis were collected at the beginning of the storage period, after 15 and 43days. At the beginning of the ensilage (time T0) the indigenous microflora was represented both by yeasts and bacteria at a concentration of about 10(6)cfu/g. During the first 15days, when the fermentation generally takes place, yeast population grew considerably (up to 10(7)cfu/g) in acidified grape marc, where bacterial population was maintained at low levels. Moreover, yeast populations recovered at the three sampling times in both treated and untreated marc were genetically characterised. This analysis showed that the species succession lead to non-Saccharomyces species dominance (in particular Issatchenkia and Pichia genera) in both conditions although acidified marc showed a lower percentage of Saccharomyces at any sampling time analysed, this meaning that non-Saccharomyces species were favoured in this environment. Gas chromatographic analysis showed a remarkable change in the aromatic profile of distilled grape marcs at the end of the storage, thus evidencing that concentration of monitored volatile compounds usually produced by microflora was generally lowered by the acidification treatment. This work demonstrates for the first time the strong effect of a persistent acidification treatment both on the microbiota of grape pomace and on the aromatic profile of the distillate. Indeed, the lowering of the pH caused significant changes in yeast-bacteria populations ratio and in yeast species turnover. These microbiological changes determine an improvement of the aromatic profile of the distillate, due to the reduction of the main volatile products associated with potential off-flavours. PMID- 22056625 TI - The reno-protective effect of a phosphoinositide 3-kinase inhibitor wortmannin on streptozotocin-induced proteinuric renal disease rats. AB - Diabetic nephropathy (DN) is a progressive kidney disease that is caused by injury to kidney glomeruli. Podocytes are glomerular epithelial cells and play critical roles in the glomerular filtration barrier. Recent studies have shown the importance of regulating the podocyte actin cytoskeleton in early DN. The phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin, simultaneously regulates Rac1 and Cdc42, which destabilize the podocyte actin cytoskeleton during early DN. In this study, in order to evaluate the reno-protective effects of wortmannin in early DN by regulating Rac1 and Cdc42, streptozotocin (STZ)-induced proteinuric renal disease (SPRD) rats were treated with wortmannin. The albuminuria value of the SPRD group was 3.55 +/- 0.56 mg/day, whereas wortmannin group was 1.77 +/- 0.48 mg/day. Also, the albumin to creatinine ratio (ACR) value of the SPRD group was 53.08 +/- 10.82 mg/g, whereas wortmannin group was 20.27 +/ 6.41 mg/g. Changes in the expression level of nephrin, podocin and Rac1/Cdc42, which is related to actin cytoskeleton in podocytes, by wortmannin administration were confirmed by Western blotting. The expression levels of nephrin (79.66 +/- 0.02), podocin (87.81 +/- 0.03) and Rac1/Cdc42 (86.12 +/- 0.02) in the wortmannin group were higher than the expression levels of nephrin (55.32 +/- 0.03), podocin (53.40 +/- 0.06) and Rac1/Cdc42 (54.05 +/- 0.04) in the SPRD group. In addition, expression and localization of nephrin, podocin and desmin were confirmed by immunofluorescence. In summary, we found for the first time that wortmannin has a reno-protective effect on SPRD rats during the early DN. The beneficial effects of wortmannin in SPRD rats indicate that this compound could be used to delay the progression of the disease during the early DN stage. PMID- 22056626 TI - Room temperature CO and H2 sensing with carbon nanoparticles. AB - We report on a shell-shaped carbon nanoparticle (SCNP)-based gas sensor that reversibly detects reducing gas molecules such as CO and H(2) at room temperature both in air and inert atmosphere. Crystalline SCNPs were synthesized by laser-assisted reactions in pure acetylene gas flow, chemically treated to obtain well-dispersed SCNPs and then patterned on a substrate by the ion-induced focusing method. Our chemically functionalized SCNP-based gas sensor works for low concentrations of CO and H(2) at room temperature even without Pd or Pt catalysts commonly used for splitting H(2) molecules into reactive H atoms, while metal oxide gas sensors and bare carbon-nanotube-based gas sensors for sensing CO and H(2) molecules can operate only at elevated temperatures. A pristine SCNP-based gas sensor was also examined to prove the role of functional groups formed on the surface of functionalized SCNPs. A pristine SCNP gas sensor showed no response to reducing gases at room temperature but a significant response at elevated temperature, indicating a different sensing mechanism from a chemically functionalized SCNP sensor. PMID- 22056627 TI - Development of an allele-specific real-time PCR assay for discrimination and quantification of p63 R279H mutation in EEC syndrome. AB - The ectrodactyly-ectodermal dysplasia-clefting syndrome is a rare autosomal dominant disorder caused by heterozygous mutations in the p63 gene, a transcription factor belonging to the p53 family. The majority of cases of ectrodactyly-ectodermal dysplasia syndrome are caused by de novo mutations and are therefore sporadic in approximately 60% of patients. The substitution of arginine to histidine (R279H), due to a c.836G>A mutation in exon 7 of the p63 gene, represents 55% of the identified mutations and is considered a mutational hot spot. A quantitative and sensitive real-time PCR was performed to quantify both wild-type and R279H alleles in DNA extracted from peripheral blood and RNA from cultured epithelial cells. Standard curves were constructed for both wild type and mutant probes. The sensitivity of the assay was determined by generating serial dilutions of the DNA isolated from heterozygous patients (50% of alleles mutated) with wild-type DNA, thus obtaining decreasing percentages of p63 R279H mutant allele (50%, 37.5%, 25%, 12.5%, 10%, 7.5%, 5%, 2.5%, and 0.0%). The assay detected up to 1% of the mutant p63. The high sensitivity of the assay is of particular relevance to prenatal diagnosis and counseling and to detect therapeutic effects of drug treatment or gene therapy aimed at reducing the amount of mutated p63. PMID- 22056628 TI - Genotype variability and clinical features of human metapneumovirus isolated from Korean children, 2007 to 2010. AB - This study was undertaken to determine the genotype variability of human metapneumovirus (hMPV) and its circulation pattern over a 3.5-year period, and to evaluate its clinical characteristics in Korean children. We investigated 4599 pediatric patients who were referred for a routine respiratory virus test by RT PCR. hMPV genotype analyses were performed using a nested PCR-restriction fragment length polymorphism assay. Clinical and laboratory data obtained from medical records were reviewed retrospectively. Of the 4599 samples tested, 325 (7.1%) were positive for hMPV, and the co-infection rate among these 325 was 16%. Nested PCR-restriction fragment length polymorphism analysis clearly identified four of the five hMPV genotypes (A2a, A2b, B1, and B2) in 97.8%. The predominant genotype of hMPV changed over the 3.5-year study period from genotype A2a to B2 and then back to A2a. The most common genotype was A2a (214/325, 65.8%). Evidence of recurrent infection was obtained in one child only. Lymphocytosis was more frequent in children with a co-infection, but sputum production was less frequent than in children with a single infection. In genotype A2a hMPV-infected children, sneezing and neutrophilia were more frequent than in genotype B1 or B2 hMPV infected children. This study broadens knowledge regarding the prevalence, the seasonal incidence, the occurrences of co-infection and re-infection, and the genotype diversity of hMPV in Korea. PMID- 22056630 TI - Does the use of standing 'hot' desks change sedentary work time in an open plan office? AB - OBJECTIVE: This study assessed the use of standing 'hot' desks in an open plan office and their impact on sedentary work time. METHOD: Australian employees (n=11; 46.9 [9.8] years; BMI 25.9 [3.5 kg/m(2)]) wore an armband accelerometer for two consecutive working weeks (November-December 2010). In the second week, employees were encouraged to use a pod of four standing 'hot' desks to stand and work as often as possible. Desk use was recorded using time logs. The percentages of daily work time spent in sedentary (<1.6 METs), light (1.6-3.0 METs) and moderate+ (>3 METs) intensity categories were calculated for each week, relative to the total daily time at work. Paired sample t tests were used to compare weekly differences. RESULTS: Employees spent 8:09 +/- 0:31h/day at work and 'hot' desk use ranged from zero to 9:35 h for the week. There were no significant changes in mean time spent in sedentary (difference of -0.1%), light (difference of 0.8%) and moderate+ (-0.7%) intensity categories. However, individual changes in sedentary work time ranged from -5.9 to 6.4%. CONCLUSIONS: Volitional use of standing 'hot' desks varied and while individual changes were apparent, desk use did not alter overall sedentary work time in this sample. PMID- 22056629 TI - Diabetes, body mass index and the excess risk of coronary heart disease, ischemic and hemorrhagic stroke in the Asia Pacific Cohort Studies Collaboration. AB - OBJECTIVE: To examine the effects of diabetes on coronary heart disease, ischemic and hemorrhagic stroke and cardiovascular disease according to category of body mass index. METHODS: Data on 161,161 men and women from 31 cohorts (baseline years, 1966-99; mean follow-up, 2-24 years) from the Asia Pacific Cohort Studies Collaboration were analyzed using Cox regression, stratified by sex and study and adjusted for age, systolic blood pressure and smoking. Diabetes was self-reported in all but one study. Body mass index was divided into five categories according to the World Health Organization Asian criteria. RESULTS: The hazard ratio (diabetes v. not) for cardiovascular disease was 1.83 (95% confidence interval, 1.66-2.01). Across body mass index categories, this hazard ratio did not change significantly (p=0.19). Similar lack of difference across body mass index groups was found for coronary heart disease (p=0.33), ischemic stroke (p=0.97) and hemorrhagic stroke (p=0.98). CONCLUSIONS: Body mass index does not modify the effect of diabetes on major cardiovascular outcomes. PMID- 22056631 TI - Longitudinal study of parental smoking habits and development of asthma in early childhood. AB - OBJECTIVE: This study examined the association between parental smoking habits and the development of asthma in early childhood by using representative samples. METHODS: The survey subjects included all of the 53,575 babies born in Japan during the periods January 10-17 and July 10-17, 2001. The families of the subjects were asked to complete questionnaires that were delivered by post at 6 months, 1 year 6 months, 2 years 6 months, 3 years 6 months, and 4 years 6 months postpartum. The first survey contained questions regarding the smoking habits of the parents. The second to fifth surveys asked if the child had needed medical attention for the treatment of asthma. RESULTS: Data from 36,888 subjects (collection rate: 68.9%) were analyzed. The 4-year cumulative incidence of asthma was 12.0%. Maternal indoor smoking significantly increased the risk of asthma development in children, 4-year risk 14.4% vs. 11.7%, risk ratio=1.24, 95% CI: 1.11 to 1.38. No statistically significant association was found between paternal smoking and asthma development in children. CONCLUSIONS: In order to prevent the development of asthma in early childhood, it is necessary to formulate measures to stop or discourage maternal smoking. PMID- 22056632 TI - Genome arrays for the detection of copy number variations in idiopathic mental retardation, idiopathic generalized epilepsy and neuropsychiatric disorders: lessons for diagnostic workflow and research. AB - We review the contributions and limitations of genome-wide array-based identification of copy number variants (CNVs) in the clinical diagnostic evaluation of patients with mental retardation (MR) and other brain-related disorders. In unselected MR referrals a causative genomic gain or loss is detected in 14-18% of cases. Usually, such CNVs arise de novo, are not found in healthy subjects, and have a major impact on the phenotype by altering the dosage of multiple genes. This high diagnostic yield justifies array-based segmental aneuploidy screening as the initial genetic test in these patients. This also pertains to patients with autism (expected yield about 5-10% in nonsyndromic and 10-20% in syndromic patients) and schizophrenia (at least 5% yield). CNV studies in idiopathic generalized epilepsy, attention-deficit hyperactivity disorder, major depressive disorder and Tourette syndrome indicate that patients have, on average, a larger CNV burden as compared to controls. Collectively, the CNV studies suggest that a wide spectrum of disease-susceptibility variants exists, most of which are rare (<0.1%) and of variable and usually small effect. Notwithstanding, a rare CNV can have a major impact on the phenotype. Exome sequencing in MR and autism patients revealed de novo mutations in protein coding genes in 60 and 20% of cases, respectively. Therefore, it is likely that arrays will be supplanted by next-generation sequencing methods as the initial and perhaps ultimate diagnostic tool in patients with brain-related disorders, revealing both CNVs and mutations in a single test. PMID- 22056633 TI - Prolonged absence of meiotic spindles by birefringence imaging negatively affects normal fertilization and embryo development. AB - Meiotic spindle (MS) assembly in human oocytes is a dynamic process that can be visualized by computer-assisted microscopy. At extrusion of the first polar body a spindle bridge is detected until the completion of telophase I and its reformation requires approximately 1h. This study analysed 396 oocytes from 112 cycles for fertilization and cleavage according to MS detection at two examinations, 39 and 41 h post-human chorionic gonadotrophin (HCG). All cycles had at least one injected oocyte lacking a visible MS at intracytoplasmic sperm injection (41 h post-HCG). To evaluate the results, oocytes were divided according to the presence (group A) or absence at both observations (group B) of the MS. Compared with group A, group B oocytes had lower normal fertilization rates, higher incidence of three pronuclei and two pronuclei in early dissolution and lower development to blastocyst. Some group A oocytes showed a late MS formation (not visualized at 39 h but at 41 h) and their performance was similar to that of the oocytes with a MS visible at both time points. Although some implantations occurred in group B, these findings suggest that prolonged MS non detection could be a marker of reduced oocyte competence. PMID- 22056634 TI - Elective single-embryo transfer: persuasive communication strategies can affect choice in a young British population. AB - This study tested the effectiveness of the framing effect and fear appeals to inform young people about the risks of multiple births and the option of selecting elective single-embryo transfer (eSET). A non-patient student sample (age (mean+/-SD) 23+/-5.5 years; n=321) were randomly allocated to one of seven groups: (1) framing effect: (1a) gain and (1b) loss frame; (2) fear appeal: (2a) high, (2b) medium and (2c) low fear; or (3) a control group: (3a) education and (3b) non-education. The primary outcome measure was the Attitudes towards Single Embryo Transfer questionnaire, before exposure to the messages (time 1) and immediately afterwards (time 2). Results revealed participants in the high fear, medium fear and gain condition demonstrated the most positive and significant differences (P<0.001 to P<0.05) in their knowledge, hypothetical intentions and modest changes in attitudes towards eSET than the low fear, loss frame and education and non-education messages. The results demonstrate that the use of complex persuasive communication techniques on a student population to promote immediate and hypothetical eSET preferences is more successful at promoting eSET than merely reporting educational content. Future research should investigate its application in a clinical population. A multiple pregnancy is a health risk to both infant and mother following IVF treatment. The aims of this study were to test the effectiveness of two persuasive communication techniques (the framing effect and fear appeals) to inform young people about the risks of multiple births and the hypothetical option of selecting elective single-embryo transfer (eSET) (i.e., only one embryo is transferred to the uterus using IVF treatment). A total of 321 non-patient student sample (mean age 23) were randomly allocated to read a message from one of seven groups: (1) framing effect: (1a) gain and (1b) loss frame; (2) fear appeal: (2a) high, (2b) medium and (2c) low fear; or (3) a control group: education (3a) and (3b) non-education. Participants completed the Attitudes towards Single Embryo Transfer questionnaire, before exposure to the messages (time 1) and immediately afterwards (time 2). Results revealed that participants in the high fear, medium fear and gain condition demonstrated the most positive and significant differences in their knowledge, hypothetical intentions and modest changes in attitudes towards eSET than the low fear, loss frame and education and non-education messages. This study recommends that health promotion based on the framing effect and fear appeals should be tested in clinical (patient) samples in the future. PMID- 22056635 TI - Legal perspectives on cross-border reproductive care. AB - Global cross-border reproductive care (CBRC), and the challenges accompanying it, are here to stay. A recent issue of this journal devoted to CBRC provides an extraordinary array of insights into multiple facets, with a focus on the legal dimensions of practices by restrictive countries such as Turkey and Italy. The articles identify restrictive laws that challenge and create vulnerabilities for both citizens and providers involved in CBRC, and call instead for more modest and nuanced legislation and the closing paper presents a thoughtful and ambitious outline for a future research agenda. This commentary reflects on the implications of these legal dimensions, including their applicability to countries with more permissive CBRC policies, discusses three specific examples of legal concerns that have arisen in the USA and identifies numerous legal issues meriting future study. Together with the nuanced, more modest legislation recommended for restrictive countries, consistent legal and judicial principles for CBRC in permissive countries would respect varying perspectives on family building while attempting to address a central legal concern of CBRC, the protection of families, third-parties and providers. Any future agenda should include research and recommendations on the legal dimensions of CBRC in both restrictive and permissive countries. PMID- 22056636 TI - Effect of family history on outcome in German patients treated with radical prostatectomy for clinically localised prostate cancer. AB - OBJECTIVE: The outcome of prostate cancer (CaP) patients treated with radical prostatectomy (RP) might be influenced by family history (FH) in a subset of patients. We analysed the effect of sporadic, familial and hereditary CaP stratified by risk on clinico-pathologic characteristics and biochemical recurrence-free survival (bRFS) following RP. MATERIALS AND METHODS: Data of 8041 German patients treated with RP between 1994 and 2008 in Germany were analysed. We evaluated the impact of FH stratified by D'Amico's risk classification on pathologic characteristics using Cochran-Mantel-Haenszel tests. The impact of FH stratified by risk on bRFS was analysed in a proportional hazards regression. RESULTS: Five thousand seven hundred and fifty six (71.6%) had sporadic, 1779 (22.1%) familial and 506 (6.3%) hereditary CaP. Adjusted for risk group, FH was associated with age of onset <65 years (p<0.001) but not with pathological characteristics or bRFS. The subgroup of patients with high risk and hereditary CaP numerically had the lowest bRFS rate at 5 (52.9%) and 10 (30.7%) years. However, this observation was statistically insignificant (p = 0.267). Familial and hereditary CaP patients were 1-2 years younger than sporadic cases at CaP diagnosis. CONCLUSION: Sporadic, familial and hereditary CaP have the same pathologic characteristics and bRFS rate following RP. Patients with a positive family history are diagnosed earlier than sporadic patients. Stratification in subgroups by risk group did not add further information. PMID- 22056637 TI - Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. AB - Adjuvant interferon has modest activity in melanoma patients at high risk for relapse. Patient selection is important; stage and ulceration of the primary tumour are key prognostic factors. METHODS: In this post hoc meta-analysis of European Organisation for Research and Treatment of Cancer (EORTC) trials 18952 (intermediate doses of interferon alpha-2b [IFN] versus observation in stage IIb III patients) and 18991 (pegylated [PEG]-IFN versus observation in stage III patients), the predictive value of ulceration on the efficacy of IFN/PEG-IFN with regard to relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) was assessed in the overall population and in subgroups stratified by stage (IIb and III-N1 [microscopic nodal disease] and III-N2 [macroscopic nodal disease]). FINDINGS: In the overall population, the comparison of IFN/PEG-IFN versus observation for RFS, DMFS and OS yielded estimated hazard ratios (HR) of 0.85 (p = 0.004), 0.89 (p = 0.04) and 0.94 (p = 0.36), respectively. The impact of treatment was greater in the ulceration group (n = 849) compared with the non-ulceration group (n = 1336) for RFS (test for interaction: p = 0.02), DMFS (p < 0.001) and OS (p < 0.001). The greatest risk reductions were observed in patients with ulceration and stage IIb/III-N1, with estimated HR for RFS, DMFS, and OS of 0.69 (p = 0.003), 0.59 (p < 0.0001) and 0.58 (p < 0.0001), respectively. The efficacy of IFN/PEG-IFN was lower in stage III-N2 patients with ulceration and uniformly absent in patients without ulceration. There was consistency between the data of both trials. INTERPRETATION: This meta-analysis of the EORTC 18952 and 18991 trials indicated that both tumour stage and ulceration were predictive factors for the efficacy of adjuvant IFN/PEG-IFN therapy. PMID- 22056638 TI - Yes-associated protein promotes tumour development in luminal epithelial derived breast cancer. AB - Yes-associated protein (YAP) is inactivated by the tumour suppressing Hippo pathway. The YAP gene is amplified in human liver cancer, and promotes tumour growth. However, there are contrasting reports about its function in breast cancer. Studies have demonstrated both oncogenic or tumour suppressor functions. Our study aims to clarify the role of YAP in breast cancer. We investigated the expression of YAP in 69 cases of human breast cancer tissue by immunohistochemistry (IHC). The role of YAP on cell growth in vitro and tumourigenesis in vivo were evaluated. We found that YAP was expressed in 75.4% (52/69) of breast cancer samples; amongst these cases YAP was overexpressed in 29% (20/69). There was no YAP expression in the remainder (17/69) cases. Breast cancer cell lines in which YAP was either overexpressed or depleted confirmed that YAP markedly promotes cell proliferation. This was confirmed in vivo: overexpression of YAP enhanced tumour formation and growth, whereas downregulation of YAP decreased the tumour formation and growth. Our results suggest that YAP acts as an oncogene in a subtype of breast cancer. PMID- 22056639 TI - Hypoxic preconditioning involves system Xc- regulation in mouse neural stem cells. AB - In animals, hypoxic preconditioning has been used as a form of neuroprotection. The exact mechanism involved in neuroprotective hypoxic preconditioning has not been described, yet could be valuable for possible neuroprotective strategies. The overexpression of the cystine-glutamate exchanger, system Xc-, has been demonstrated as being neuroprotective (Shih, Erb et al. 2006). Here, using immunohistochemistry, we demonstrate that C57BL/6 mice exposed to hypoxia showed an increase in system Xc- expression, with the highest level of intensity in the hippocampus. Western Blot analysis also showed an almost 2-fold increase in system Xc- protein in hypoxia-exposed versus control mice. The mRNA for the regulatory subunit of system Xc-, xCT, and the xCT/actin ratio were also increased under hypoxic conditions. Experiments using hypoxia-inducible factor (HIF-1alpha) siRNA showed a statistically significant decrease in HIF-1alpha and system Xc- expression. Under hypoxic conditions, system Xc- activity, as determined by cystine uptake, increased 2-fold. Importantly, hypoxic preconditioning was attenuated in neural stem cells by pharmacological inhibition of system Xc- activity with S4-carboxyphenylglycine. These data provide the first evidence of hypoxic regulation of the cystine glutamate exchanger system Xc-. PMID- 22056640 TI - Survival time of cardiac allografts prolonged by isogeneic BMT in mice. AB - To find an approach to prolong the survival time of cardiac allografts in a BALB/c-to-C57/BL6 heterotopic heart transplant model and to try to figure out related chemokines and cytokines, isogeneic and allogeneic BM cells were obtained from pregnant C57/BL6 (?C57/BL6 * ?BALB/c) and regular BALB/c mice and injected to the half lethally irradiated C57/BL6 mice 1 day before heart transplantation. Recipients were treated with CsA or phosphate-buffered saline for 7 days. Isogeneic BMT (iBMT) from pregnant C57/BL6 mice was observed to significantly prolong the survival of BALB/c allografts and reduce the lymphocyte infiltration. Allogeneic BMT (aBMT) and iBMT both exhibited signicantly less T-cell proliferation reactivity and the similar degree of chimerism. There was no significant difference in these groups of IFN-gamma and IL-4 production. The level of chemokine MIG (CXCL9) dramatically decreased in aBMT and iBMT groups compared with the control group. But there were no significant differences between aBMT and iBMT group. IL-17 and RORgamma(t) (receptor-related orphan receptor) production were downregulated in iBMT recipients. These results indicate that iBMT can prolong the survival of cardiac allografts. IL-17 production downregulated in iBMT recipients. This means that iBMT may have important therapeutic implications. PMID- 22056641 TI - Prevention of relapse using granulocyte CSF-primed PBPCs following HLA mismatched/haploidentical, T-cell-replete hematopoietic SCT in patients with advanced-stage acute leukemia: a retrospective risk-factor analysis. AB - The role of donor lymphocyte infusion (DLI) in the prophylaxis of relapse has not been defined. We retrospectively analyzed the data from 88 patients with advanced stage acute leukemia after HLA-mismatched/haploidentical hematopoietic SCT (HSCT) whose treatment did (n=61) or did not (n=27) include granulocyte CSF (GCSF) primed PBPCs infusion (GPBPCI). The two groups were compared with respect to relapse and OS. Further, a detailed analysis of risk factors was performed. The 2 year cumulative incidence of relapse in patients receiving prophylactic GPBPCI and not receiving prophylactic GPBPCI were 36% and 55% (P=0.017), respectively. Estimated survival at 3 years was 31% for patients receiving prophylactic GPBPCI and 11% for patients not receiving prophylactic GPBPCI (P=0.001). The three-year probability of leukemia-free survival was also higher in patients who received prophylactic GPBPCI (22%) compared with patients who did not (11%) (P=0.003). Multivariate analysis for relapse showed that use of prophylactic GPBPCI after transplantation was an independent prognostic factor (P=0.025). Higher OS was associated with use of prophylactic GPBPCI (P=0.002), AML (P=0.027) and female sex (P=0.023). Our results suggest that use of prophylactic GPBPCI may increase survival of patients with advanced-stage acute leukemia who receive HLA mismatched/haploidentical HSCT. PMID- 22056642 TI - Racial disparities in hematopoietic cell transplantation in the United States. AB - Hematopoietic cell transplantation (HCT) is a highly specialized, expensive and resource-intense medical procedure that can be associated with racial disparities. We review the prevailing literature on racial disparities in HCT in the United States and describe areas for future research and interventions. We discuss the complexity of interpreting race as a biological and social determinant of disease in biomedical research, especially as it relates to HCT. In the United States, race is often a surrogate for socioeconomic, education and health insurance status. We also discuss some of the nuances to consider while reviewing the literature on racial disparities. Disparities by race exist in three areas related to HCT: donor availability, access to HCT and outcomes of HCT. African-Americans/Blacks have a lower likelihood of finding an unrelated donor. Race and ethnicity definitions are country-specific and reconciling race data can represent significant challenges to unrelated donor registries worldwide. African-Americans/Blacks do not have the same access to autologous and allogeneic HCT as Whites. Racial disparities in outcomes of HCT are more prevalent among allogeneic HCT than autologous HCT recipients. More research is required to understand the biological, social, cultural, medical and financial aspects of race that may influence access to HCT and survival after transplantation. Better understanding of racial disparities will minimize inequities, inform health policy, guide development of interventions targeted to eliminate disparities and ensure equitable access to HCT for all populations. PMID- 22056643 TI - Glans penis involvement: an under-recognized manifestation of chronic GVHD. PMID- 22056644 TI - Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results. AB - The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (AHCT) in advanced multiple sclerosis (MS). TBI, CY and antithymocyte globulin were followed by transplantation of autologous, CD34-selected PBSCs. Neurological examinations, brain magnetic resonance imaging and cerebrospinal fluid (CSF) for oligoclonal bands (OCB) were serially evaluated. Patients (n=26, mean Expanded Disability Status Scale (EDSS)=7.0, 17 secondary progressive, 8 primary progressive, 1 relapsing/remitting) were followed for a median of 48 months after HDIT followed by AHCT. The 72-month probability of worsening >=1.0 EDSS point was 0.52 (95% confidence interval, 0.30-0.75). Five patients had an EDSS at baseline of <=6.0; four of them had not failed treatment at last study visit. OCB in CSF persisted with minor changes in the banding pattern. Four new or enhancing lesions were seen on MRI, all within 13 months of treatment. In this population with high baseline EDSS, a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant. Non-inflammatory events may have contributed to neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS. PMID- 22056645 TI - Nipple sparing mastectomy: can we predict the factors predisposing to necrosis? AB - BACKGROUND: Nipple sparing mastectomy (NSM) is an accepted surgical approach in selected breast cancer and prophylactic mastectomy, nevertheless post-mastectomy skin necrosis is one of the frequent complications. This study aimed to analyze the factors that may lead to skin necrosis after NSM. PATIENTS AND METHODS: From May 2010 to July 2010, we prospectively registered 50 consecutive NSM from 45 patients. There were 40 mastectomies for cancer, and 10 prophylactic mastectomies. The various patient's and surgical factors were registered during pre-, intra- and postoperative period. RESULTS: No total necrosis of the nipple areola complex (NAC) was observed. There were thirteen cases with partial necrosis (26.0%) of the areola or the adjacent skin. All these necrosis were partial both for the surface and the thickness. Surgical debridement was performed in 9 (18.0%) cases. The significant risk factors are smoking, young age, type of incision and NAC involvement with areola flap thickness less than 5 mm. CONCLUSION: NSM should be done with high caution in smokers. Young patients, periareolar incision and superior circumareolar incision have also a higher risk of necrosis. We recommend keeping areolar flap thickness more than 5 mm in areola region. PMID- 22056646 TI - Temporal pattern of recurrence of stage I endometrial cancer in relation to histological risk factors. AB - OBJECTIVE: To study the temporal pattern of endometrial cancer recurrence in relation to histological risk factors in a large multicenter setting. METHODS: 843 patients with apparent stage I endometrial cancer were followed for a median time of 38 months, documenting all recurrences. Patients were stratified as high risk based on the presence of at least one of the established histological risk factors: high tumor grade, penetration to the outer half of the myometrium, lymphvascular space involvement, lower uterine segment involvement and non endometroid histology. Survival analysis, including Kaplan-Meier curves, log-rank tests and multi-variate Cox proportional hazard regression were used to evaluate the equality of recurrence-free distributions for different levels of risk. RESULTS: Recurrence was documented in 66 cases. The presence of one or more of the histological risk factors was associated with significantly shorter recurrence free survival, not attenuating over time (p < 0.001). Age-adjusted Cox regression model demonstrated a significantly decreased recurrence-free survival (HR = 2.8 95% CI 1.5, 5.1) in the presence of risk factors. CONCLUSIONS: In patients with stage I endometrial cancer, the presence of histological risk factors is associated with a significantly higher recurrence rate, which does not attenuate over follow up time. This may allow for a selective approach in the follow- up of endometrial cancer patients. PMID- 22056647 TI - Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin nicotinamide generated oxidative stress induced diabetic rats. AB - Oxidative stress has been suggested as a contributory factor in development and complication of diabetes. The aim of the study was to evaluate the effect of diosmin (DS) in oxidative stress in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats by measuring the lipid peroxidation (LPO) as well as the ameliorative properties. Experimental diabetes was induced by a single intraperitoneal (i.p) injection of STZ (45 mg/kg body weight (b.w.)) dissolved in 0.1 mol/L citrate buffer (pH 4.5), 15 min after the i.p administration of NA (110 mg/kg b.w.). Diabetic rats exhibited increased plasma glucose with significant decrease in plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and the levels of low-molecular weight antioxidants vitamin C, vitamin E and reduced glutathione (GSH) were decreased while increases in the levels of LPO markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with DS (100mg/kg/day) for a period of 45 days showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. These results indicated that DS has potential ameliorative effects in addition to its antidiabetic effect in type 2 diabetic rats. PMID- 22056648 TI - Analysis of an unusual cluster of systemic reactions to subcutaneous specific immunotherapy with respiratory allergens in one allergy center. AB - Systemic reactions to subcutaneous immunotherapy occur despite all necessary precautions and experienced staff and should prompt a search for causative factors. We present an analysis of 11 reactions, 8 of them within a short period. The patients and reactions were evaluated regarding extract errors (composition, concentration), dosing errors, ignored contraindications to specific subcutaneous immunotherapy, introductions versus maintenance phase and accidental intravascular injection. No single or common cause could be identified. Statistical analysis suggests that exceptional clusters of systemic reactions such as these may be just random cumulations without identifiable cause. PMID- 22056649 TI - MeCP2 controls the expression of RASAL1 in the hepatic fibrosis in rats. AB - Hepatic stellate cells (HSCs) activation is an essential event during liver fibrogenesis. A major pathway is the transition of HSCs into hepatic myofibroblasts. The methyl-CpG-binding protein MeCP2 which promotes repressed chromatin structure is selectively detected in myofibroblasts of diseased liver. Overexpression of this protein results in an increase of global methylation levels. Treatment of HSCs with DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC) blocks the cell proliferation. 5-azadC also prevents loss of Ras GTPase activating-like protein 1 (RASAL1) expression that occurs during HSCs proliferation. To further explore the underlying molecular mechanisms, we hypothesized that this perpetuation of fibrogenesis was caused by DNA methylation. Results demonstrated that hypermethylation of RASAL1 is associated with the perpetuation of fibroblast activation and fibrogenesis in the liver. knockdown of MeCP2 using siRNA technique increased RASAL1 in both mRNA and protein level in myofibroblasts. These studies demonstrated that MeCP2 and DNA methylation may provide molecular mechanisms for perpetuated fibroblast activation and fibrogenesis in the liver. PMID- 22056651 TI - Linear-quadratic order parameter coupling and multiferroic phase transitions. AB - The coupling between order parameters in systems with several instabilities has been analysed within Landau theory. The dominant term considered in this paper is linear in one order parameter and quadratic in the second order parameter ~QP2; other coupling terms have been treated previously. Typical examples for Q are proper or pseudo-proper ferroelastic instabilities, while P might be octahedral tilting in a perovskite, (anti-)ferromagnetic ordering or (anti-)ferroelectric soft modes. Coupling of this type is common in fluorites, Verwey transitions, Jahn-Teller systems, pnictide superconductors, etc. Analytical solutions and characteristic phase diagrams of the stable configurations are compiled. The coupling can lead to stepwise phase transitions even when the uncoupled systems would show continuous transitions. Mixed phases are common, so that many 'intermediate phases' described in the literature may be the result of this linear-quadratic coupling. PMID- 22056650 TI - Environmental cigarette smoke exposure modulates IgE levels of Pb-exposed children. AB - In urban areas with a predominance of early to mid-20th century housing stock, islands of children possessing blood lead levels (PbB) in excess of CDC guidelines (>10MUg/dL) exist. Many of these children are also exposed to environmental tobacco smoke (ETS). The current study examined the impact of Pb exposure (PbB levels of 1-55MUg/dL) with/without concurrent ETS exposure on immune system function in 318 children aged 6-84 months from the urban area of Springfield-Greene County, MO. In this population, 36.5% of children possessed PbB levels >10MUg/dL, 62.9% of children came from smoking homes, 51.9% of children were under 2 years of age, and the population was WIC eligible and predominantly of white, non-Hispanic ethnicity. Multiple immune function markers including cell counts, IgE levels, sCD25 (sIL2R) and IL4 concentrations, and titers to common childhood immunizations were analyzed for correlation with Pb and/or ETS exposure. Increased IgE levels (p<0.01) were found in children with PbB levels within CDC Classes II-IV - this finding was primarily attributable to elevated IgE levels in the subpopulation of children with concurrent Pb and ETS exposure. A trend (0.05 .27) were observed, and no subjects exhibited changes in laboratory test or ECG results at follow-up that were deemed clinically important or required intervention. Most subjects (91%) did experience transient xenon related symptoms, most commonly dizziness (59%), paresthesia (34%), euphoria (30%), and hypoesthesia (30%). All symptoms resolved without clinical intervention in 1.6 minutes +/- 0.9. CONCLUSION: Inhalation of hyperpolarized (129)Xe is well tolerated in healthy subjects and in those with mild or moderate COPD. Subjects do experience mild, transient, xenon-related symptoms, consistent with its known anesthetic properties. PMID- 22056684 TI - Anomalous origin of the right coronary artery from the left coronary sinus with an interarterial course: subtypes and clinical importance. AB - PURPOSE: To classify anomalous origins of the right coronary artery (RCA) from the left coronary sinus (AORL) with an interarterial course into two subtypes and to evaluate the clinical importance of each. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study, and informed consent was waived. Through a retrospective review of 22,925 consecutive cardiac computed tomographic (CT) scans, 124 cases of AORL with an interarterial course were identified. These anomalies were classified into two subtypes according to the location of the anomalous RCA ostium: high interarterial course (between the aorta and the pulmonary artery) and low interarterial course (between the aorta and the right ventricular outflow tract). The clinical records were evaluated, and differences in prevalence of typical angina and major adverse cardiac events (MACEs) between the subtypes were analyzed through the chi(2) contingency tables or Fisher exact test. RESULTS: After excluding patients with combined cardiac disease, 87 patients (51 [59%] men, 36 [41%] women; mean age, 56.0 years) were enrolled. Of the 87 patients, 53 had a high interarterial course and 34 had a low interarterial course. A significant difference in the prevalence of typical angina (high [43%] vs low [6%], P = .001) and MACE (high [28%] vs low [6%], P = .012) was observed between the two subtypes. For patients with a high interarterial course, the odds ratio for typical angina was 12.3 (95% confidence interval: 2.7, 56.6), and the odds ratio for MACE was 6.3 (95% confidence interval: 1.3, 29.7). CONCLUSION: The prevalence of typical angina and that of MACE were significantly higher in patients with a high interarterial course than in those with a low interarterial course. PMID- 22056685 TI - Sodium MR imaging of Achilles tendinopathy at 7 T: preliminary results. AB - PURPOSE: To investigate the feasibility of sodium magnetic resonance (MR) imaging in the diagnosis of Achilles tendinopathy. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Twenty healthy volunteers and eight patients with Achilles tendinopathy were examined by using a 7-T whole-body MR imager with a 15-channel sodium knee coil. The sodium signal-to noise ratio (SNR) from each region, as well as from the whole Achilles tendon, was compared between patients and healthy control subjects. The changes in SNR were assessed with a two-tailed unpaired t test in three regions of the Achilles tendon: the insertion area, the middle portion, and the muscle-tendon junction. P values less than .05 were considered to indicate a statistically significant difference. To validate a relationship between the sodium SNR and the glycosaminoglycan content in tendon, five cadaver ankles were examined with MR imaging and immunohistologically. The Pearson correlation coefficient between sodium SNR and glycosaminoglycan content was calculated. RESULTS: Significant differences (P < .05) in the mean sodium SNR of healthy control subjects (mean SNR, 4.9 +/- 2.1 [standard deviation]) and patients with chronic Achilles tendinopathy (mean SNR, 9.3 +/- 2.3) were observed. Similar results were found at the insertion (mean SNR in control subjects, 6.7 +/- 2.3; mean SNR in patients, 12.3 +/- 4.5; P < .05) and the midportion (mean SNR in control subjects, 5.1 +/- 1.9; mean SNR in patients, 9.4 +/- 3.0; P < .05) of the Achilles tendon. At the muscle-tendon junction, the sodium SNR difference between control subjects and patients was small but still bellow the significance level (P = .0137). The increase in sodium SNR was observed in all regions independently of the location of morphologic findings. The Pearson correlation coefficient between sodium SNR and glycosaminoglycan content was 0.71. CONCLUSION: Sodium MR imaging may allow detection of the proteoglycan content increase in Achilles tendinopathy and thus identify the biochemical changes in the early stages of tendinopathy. PMID- 22056686 TI - Peripheral nerve repair: monitoring by using gadofluorine M-enhanced MR imaging with chitosan nerve conduits with cultured mesenchymal stem cells in rat model of neurotmesis. AB - PURPOSE: To observe the longitudinal changes of nerve repair in rats after tissue engineered construct implantation at magnetic resonance (MR) imaging and to determine whether the enhanced nerve regeneration with use of tissue-engineered constructs could be monitored with gadofluorine M-enhanced MR imaging or nerve T2 relaxation time measurement. MATERIALS AND METHODS: All experimental protocols were approved by the institutional Animal Use and Care Committee. Tissue engineered constructs were prepared by seeding mesenchymal stem cells (MSCs) into chitosan nerve tubes. Thirty-six rats with sciatic nerve transection injury underwent nerve tube implantation with (n = 18) or without (n = 18) MSC seeding. Sequential T2 measurement, gadofluorine M-enhanced MR imaging, and sciatic function index measurement were performed over an 8-week follow-up period, with histologic assessments performed at regular intervals. T2 relaxation times and signal intensity at gadofluorine M-enhanced T1-weighted imaging were measured and were compared by using repeated-measures analysis of variance followed by the Student-Neuman-Keuls post-hoc test for multiple pairwise comparisons. RESULTS: Nerve T2 relaxation times and gadofluorine M enhancement, as well as functional changes, showed a similar time course. Nerves implanted with MSC-seeded tubes achieved slightly better functional recovery and enhanced nerve regeneration while showing a slower return to baseline T2 relaxation time and a more rapid decline in gadofluorine M enhancement compared with nerves implanted with chitosan tubes alone. T2 values of the distal portion of transected nerves showed a more rapid return to baseline level than did gadofluorine M enhancement. CONCLUSION: Peripheral nerve repair with use of tissue-engineered constructs can be monitored by using gadofluorine M-enhanced MR imaging and T2 relaxation time measurements. T2 relaxation time seems more sensitive than gadofluorine M enhanced MR imaging for detecting nerve regeneration. PMID- 22056687 TI - Correlation of contrast-detail analysis and clinical image quality assessment in chest radiography with a human cadaver study. AB - PURPOSE: To determine the correlation between the clinical and physical image quality of chest images by using cadavers embalmed with the Thiel technique and a contrast-detail phantom. MATERIALS AND METHODS: The use of human cadavers fulfilled the requirements of the institutional ethics committee. Clinical image quality was assessed by using three human cadavers embalmed with the Thiel technique, which results in excellent preservation of the flexibility and plasticity of organs and tissues. As a result, lungs can be inflated during image acquisition to simulate the pulmonary anatomy seen on a chest radiograph. Both contrast-detail phantom images and chest images of the Thiel-embalmed bodies were acquired with an amorphous silicon flat-panel detector. Tube voltage (70, 81, 90, 100, 113, 125 kVp), copper filtration (0.1, 0.2, 0.3 mm Cu), and exposure settings (200, 280, 400, 560, 800 speed class) were altered to simulate different quality levels. Four experienced radiologists assessed the image quality by using a visual grading analysis (VGA) technique based on European Quality Criteria for Chest Radiology. The phantom images were scored manually and automatically with use of dedicated software, both resulting in an inverse image quality figure (IQF). Spearman rank correlations between inverse IQFs and VGA scores were calculated. RESULTS: A statistically significant correlation (r = 0.80, P < .01) was observed between the VGA scores and the manually obtained inverse IQFs. Comparison of the VGA scores and the automated evaluated phantom images showed an even better correlation (r = 0.92, P < .001). CONCLUSION: The results support the value of contrast-detail phantom analysis for evaluating clinical image quality in chest radiography. PMID- 22056688 TI - Cerebral microbleeds: burden assessment by using quantitative susceptibility mapping. AB - PURPOSE: To assess quantitative susceptibility mapping (QSM) for reducing the inconsistency of standard magnetic resonance (MR) imaging sequences in measurements of cerebral microbleed burden. MATERIALS AND METHODS: This retrospective study was HIPAA compliant and institutional review board approved. Ten patients (5.6%) were selected from among 178 consecutive patients suspected of having experienced a stroke who were imaged with a multiecho gradient-echo sequence at 3.0 T and who had cerebral microbleeds on T2*-weighted images. QSM was performed for various ranges of echo time by using both the magnitude and phase components in the morphology-enabled dipole inversion method. Cerebral microbleed size was measured by two neuroradiologists on QSM images, T2*-weighted images, susceptibility-weighted (SW) images, and R2* maps calculated by using different echo times. The sum of susceptibility over a region containing a cerebral microbleed was also estimated on QSM images as its total susceptibility. Measurement differences were assessed by using the Student t test and the F test; P < .05 was considered to indicate a statistically significant difference. RESULTS: When echo time was increased from approximately 20 to 40 msec, the measured cerebral microbleed volume increased by mean factors of 1.49 +/- 0.86 (standard deviation), 1.64 +/- 0.84, 2.30 +/- 1.20, and 2.30 +/- 1.19 for QSM, R2*, T2*-weighted, and SW images, respectively (P < .01). However, the measured total susceptibility with QSM did not show significant change over echo time (P = .31), and the variation was significantly smaller than any of the volume increases (P < .01 for each). CONCLUSION: The total susceptibility of a cerebral microbleed measured by using QSM is a physical property that is independent of echo time. PMID- 22056690 TI - Construction of two vectors for gene expression in Trichoderma reesei. AB - We report the construction of two filamentous fungi Trichoderma reesei expression vectors, pWEF31 and pWEF32. Both vectors possess the hygromycin phosphotransferase B gene expression cassette and the strong promoter and terminator of the cellobiohydrolase 1 gene (cbh1) from T. reesei. The two newly constructed vectors can be efficiently transformed into T. reesei with Agrobacterium-mediated transformation. The difference between pWEF31 and pWEF32 is that pWEF32 has two longer homologous arms. As a result, pWEF32 easily undergoes homologous recombination. On the other hand, pWEF31 undergoes random recombination. The applicability of both vectors was tested by first generating the expression vectors pWEF31-red and pWEF32-red and then detecting the expression of the DsRed2 gene in T. reesei Rut C30. Additionally, we measured the exo-1,4-beta-glucanase activity of the recombinant cells. Our work provides an effective transformation system for homologous and heterologous gene expression and gene knockout in T. reesei. It also provides a method for recombination at a specific chromosomal location. Finally, both vectors will be useful for the large scale gene expression industry. PMID- 22056689 TI - Quantification and monitoring of inflammation in murine inflammatory bowel disease with targeted contrast-enhanced US. AB - PURPOSE: To evaluate ultrasonography (US) by using contrast agent microbubbles (MBs) targeted to P-selectin (MB(P-selectin)) to quantify P-selectin expression levels in inflamed tissue and to monitor response to therapy in a murine model of chemically induced inflammatory bowel disease (IBD). MATERIALS AND METHODS: All procedures in which laboratory animals were used were approved by the institutional administrative panel on laboratory animal care. Binding affinity and specificity of MB(P-selectin) were tested in cell culture experiments under flow shear stress conditions and compared with control MBs (MB(Control)). In vivo binding specificity of MB(P-selectin) to P-selectin was tested in mice with trinitrobenzenesulfonic acid-induced colitis (n = 22) and control mice (n = 10). Monitoring of anti-tumor necrosis factor alpha antibody therapy was performed over 5 days in an additional 30 mice with colitis by using P-selectin-targeted US imaging, by measuring bowel wall thickness and perfusion, and by using a clinical disease activity index score. In vivo targeted contrast material-enhanced US signal was quantitatively correlated with ex vivo expression levels of P-selectin as assessed by quantitative immunofluorescence. RESULTS: Attachment of MB(P selectin) to endothelial cells was significantly (P = .0001) higher than attachment of MB(Control) and significantly (rho = 0.83, P = .04) correlated with expression levels of P-selectin on endothelial cells. In vivo US signal in mice with colitis was significantly higher (P = .0001) with MB(P-selectin) than with MB(Control). In treated mice, in vivo US signal decreased significantly (P = .0001) compared with that in nontreated mice and correlated well with ex vivo P selectin expression levels (rho = 0.69; P = .04). Colonic wall thickness (P >= .06), bowel wall perfusion (P >= .85), and clinical disease activity scoring (P >= .06) were not significantly different between treated and nontreated mice at any time. CONCLUSION: Targeted contrast-enhanced US imaging enables noninvasive in vivo quantification and monitoring of P-selectin expression in inflammation in murine IBD. PMID- 22056691 TI - Characteristics of Mycobacterium smegmatis J15cs strain lipids. AB - Mycobacterium smegmatis is a rapidly growing, non-pathogenic mycobacterium, and M. smegmatis strain mc(2)155 in particular has been used as a tool for molecular analysis of mycobacteria because of its high rate of transformation. We examined another strain, M. smegmatis J15cs, which has the advantage of surviving for six days in murine macrophages. The J15cs strain produces a rough dry colony, and we hypothesized that the long survival of the J15cs strain was correlated with its cell wall components. Therefore, the lipid compositions of these two strains were compared. The subclasses and carbon species of the mycolic acids were very similar, and the major glycolipids and phospholipids were expressed in both strains. However, apolar glycopeptidolipids were deleted only in the J15cs strain. The presence of apolar glycopeptidolipids gives the cell wall a different structure. Moreover, the apolar glycopeptidolipids were recognized by macrophages via toll-like receptor 2, but not 4. We concluded that the absence of apolar glycopeptidolipids is a definitive feature of the J15cs strain, and affects its morphology and survival in host cells. PMID- 22056692 TI - Implementation of a multi-parameter Point-of-Care-blood test analyzer reduces central laboratory testing and need for blood transfusions in very low birth weight infants. AB - Blood sampling for laboratory testing is a major cause of iatrogenic blood loss and anemia in neonatal intensive care unit [NICU] patients. The objective of the study was to assess whether the implementation of a multi-parameter Point of Care Test [POCT] (Roche, Cobas b221) analyzer affected blood loss for central laboratory testing and need for red blood cell transfusion in our NICU. This was a retrospective observational cohort study in a NICU with comparison of two serial cohorts of 2 years each. Implementation of a multi-parameter POCT decreased central laboratory performed testing for bilirubin (-32% per patient) and electrolytes (-36% per patient). On average, the net blood volume taken per admitted patient for electrolyte testing decreased with 23.7% and 22.2% for bilirubin testing in the second cohort. After implementation of POCT, fewer very low birth weight infants [VLBWI] required blood transfusion (38.9% vs. 50%, p<.05) as the number of transfusion/infants decreased by 48% (1.57 vs. 2.53, p<0.01). The implementation of POCT was cost-efficient for the Belgian national health insurance, cost reduction -8.3% per neonate. We conclude that implementation of a bedside multi-parameter POCT analyzer decreases transfusions among VLBWI by reducing iatrogenic blood loss for central laboratory testing. PMID- 22056693 TI - Enabling semantic similarity estimation across multiple ontologies: an evaluation in the biomedical domain. AB - The estimation of the semantic similarity between terms provides a valuable tool to enable the understanding of textual resources. Many semantic similarity computation paradigms have been proposed both as general-purpose solutions or framed in concrete fields such as biomedicine. In particular, ontology-based approaches have been very successful due to their efficiency, scalability, lack of constraints and thanks to the availability of large and consensus ontologies (like WordNet or those in the UMLS). These measures, however, are hampered by the fact that only one ontology is exploited and, hence, their recall depends on the ontological detail and coverage. In recent years, some authors have extended some of the existing methodologies to support multiple ontologies. The problem of integrating heterogeneous knowledge sources is tackled by means of simple terminological matchings between ontological concepts. In this paper, we aim to improve these methods by analysing the similarity between the modelled taxonomical knowledge and the structure of different ontologies. As a result, we are able to better discover the commonalities between different ontologies and hence, improve the accuracy of the similarity estimation. Two methods are proposed to tackle this task. They have been evaluated and compared with related works by means of several widely-used benchmarks of biomedical terms using two standard ontologies (WordNet and MeSH). Results show that our methods correlate better, compared to related works, with the similarity assessments provided by experts in biomedicine. PMID- 22056694 TI - Boosting performance of gene mention tagging system by hybrid methods. AB - NER (Named Entity Recognition) in biomedical literature is presently one of the internationally concerned NLP (Natural Language Processing) research questions. In order to get higher performance, a hybrid experimental framework is presented for the gene mention tagging task. Six classifiers are firstly constructed by four toolkits (CRF++, YamCha, Maximum Entropy (ME) and MALLET) with different training methods and features sets, and then combined with three different hybrid methods respectively: simple set operation method, voting method and two layer stacking method. Experiments carried out on the corpus of BioCreative II GM task show that the three hybrid methods get the F-measure of 87.40%, 87.31% and 87.70% separately without any post-processing, which are all higher than those of any single ones. Our best hybrid method (two layer stacking method) achieves an F measure of 88.42% after post-processing, which outperforms most of the state-of the-art systems. We also discuss the influence on the performance of the ensemble system by the number, performance and divergence of single classifiers in each hybrid method, and give the corresponding analysis why our hybrid models can improve the performance. PMID- 22056695 TI - The impact of salt water soaks on biophysical and molecular parameters in psoriatic epidermis equivalents. AB - BACKGROUND/AIMS: The exact mechanisms of action of balneophototherapy are incompletely understood. We aimed to investigate the effect of salt water soaks on ultraviolet (UV) transmission and the expression of molecular parameters of psoriasis. METHODS: We studied UV transmission and the expression of antimicrobial peptides and skin-derived antileukoproteinase (SKALP/elafin) in psoriatic epidermis equivalents which were pretreated with tap water and differently concentrated salt water solutions. Moreover, we performed in vivo phototoxicity tests in healthy subjects. RESULTS: Highly concentrated salt water soaks significantly increase UV transmission through psoriatic epidermis equivalents, in particular within the wavelength range of 305- 360 nm. In vivo tests revealed increased photosensitivity following highly concentrated salt water baths. A significant decrease in human beta-defensin-2 (hBD-2) and SKALP/elafin is observed after highly concentrated NaCl soaks. CONCLUSION: An increase in UV transmission following highly concentrated salt water soaks likely causes enhanced UV gain within the viable epidermis. Moreover, our data indicate that salt water soaks seem to influence the protein profiles of hBD-2 and SKALP/elafin. PMID- 22056696 TI - Forearm reconstruction with bone allograft following tumor excision: a series of 10 patients with a mean follow-up of 10 years. AB - BACKGROUND: After a tumor resection, the reestablishment of the bone continuity at the forearm remains a challenge for restoring the biomechanics of hand and elbow. Bone allograft might be one option to consider amongst other suitable alternatives but there are insufficient data available to substantiate its value. PATIENTS AND METHODS: We retrospectively investigated a series of 10 consecutive patients that had presented a bone tumor at the forearm. After bone excision, the segmental loss was replaced either by a bone allograft or an osteochondral allograft. Patients were reviewed clinically and with radiographs. RESULTS: The mean follow-up was 110 +/- 99 months. Fracture of the allograft was the most prevalent complication occurring in four patients, mainly in the osteoarticular group. Four patients were surgically revised: two of them had a fracture of the allograft that required a new one, another one had a painful stiff wrist requiring removal of the allograft and arthrodesis with autograft and the fourth one had a non-union of an intercalary allograft that was treated by a distal ulnar joint resection. Intercalary allograft had fewer complications than osteoarticular allografts and they had a better functional MSTS score with an average of 79% of a normal function compared to osteoarticular allografts with an average score of 62%. There was no infection. At the latest follow-up, one reconstruction of the forearm with an allograft failed and concerned the distal radius joint. DISCUSSION: A bone allograft when available can be considered as one amongst other suitable options for the reconstruction of the forearm skeleton. PMID- 22056697 TI - The valence strength of unpleasant emotion modulates brain processing of behavioral inhibitory control: neural correlates. AB - As an ability critical for adaptive social living, behavioral inhibitory control (BIC) is known to be influenced substantially by unpleasant emotion. Nevertheless, how unpleasant emotion of diverse strength influences this control, and the spatiotemporal dynamics underlying this influence, remain undetermined. For this purpose, Event-related potentials (ERPs) were recorded for standard stimulus which required no BIC, and for deviant stimuli that required controlling habitual responses, during highly unpleasant (HU), mildly unpleasant (MU) and Neutral blocks. The results showed delayed response latencies for deviant compared to standard stimuli, irrespective of emotionality. Moreover, there were significant main effects of stimulus type, and significant stimulus type and block interaction effects on the averaged amplitudes of the 230-310 ms and 330 430 ms intervals. In the deviant-standard difference waves which directly index BIC-relevant processing, these interactions were manifested by increased negative potentials as a function of the strength of unpleasant emotion across N2 and P3 components. In addition, these influences are specific to unpleasant emotion, as pleasant emotion of diverse strength produced a similar impact in the control experiment. Therefore, unpleasant emotion of diverse strength is different in impact on brain processing of behavioral inhibitory control. This impact is evident not only in early monitoring of response conflicts, but also in late processing of response inhibition. PMID- 22056698 TI - Identification and characterization of low temperature stress responsive genes in Poncirus trifoliata by suppression subtractive hybridization. AB - Trifoliate orange (Poncirus trifoliata (L.) Raf.) is extremely cold hardy when fully acclimated, but knowledge relevant to the molecular events underlying the acclimation is still limited so far. In this study, forward (4 degrees C over 25 degrees C) and reverse (25 degrees C over 4 degrees C) suppression subtractive hybridization (SSH) libraries were constructed in order to identify the genes involved in cold acclimation in trifoliate orange. After reverse northern blotting analysis and sequencing, a total of 105 and 117 non-redundant differentially expressed sequence tags (ESTs) were obtained from the forward and reverse libraries, respectively. Blast2go analysis revealed that 91 ESTs, 31 from the forward library and 60 from the reverse library, displayed significant sequence homology to the genes with known or putative functions. They were categorized into various functional groups, including catalytic activity, binding protein, structural molecule, enzyme regulator, molecular transducer, electron carrier, and transport activity/transcription regulation. Expression analysis of the selected ESTs by reverse transcriptase polymerase chain reaction was consistent with the results of differential screening. In addition, time-course expression patterns of the genes further confirmed that they were responsive to low temperature treatment. Among the genes of known functions, many are related to maintenance of cell wall integrity, adjustment of osmotic potential and maintenance of reactive oxygen species homeostasis, implying that these physiological processes might be of paramount significance in rendering protective mechanisms against the low temperature stress. The data presented here gain an insight into the molecular changes underlying the cold acclimation of trifoliate orange, and the results can be of reference for unraveling candidate genes that hold great potential for genetic engineering in an effort to create novel germplasms with enhanced cold stress tolerance. PMID- 22056699 TI - SuperPartitions: detection and classification of orthologs. AB - The proper detection of orthologs is crucial for evolutionary studies of genes and species. Despite large efforts to solve this problem the methodological situation appears unsettled to a large extent and the "quest for orthologs" is still an ongoing task in large-scale genome comparisons. Here, we introduce a simple operational framework for the detection of orthologs and their classification. The operational framework relies on well-established principles, optimizing their implementation for the considered purposes, and chaining components in coherent procedures: 1) We take advantage of the efficiency and simplicity of the Reciprocal Best Hit (RBH) detections, remedying (by design) the drawback concerning the limitations in terms of 1:1 detections. The procedure is based on the partitioning of Reciprocal Best Hits, with the further merging of partitions including members of the same paralogous classes ("SuperPartition of Orthologs" (SPOs)). 2) We then resort to the conservation profiles of the obtained clusters, allowing simple detection of SPOs containing duplicated members. Based on accepted evolutionary principles, such members can be further tagged as in-paralogs (co-orthologs) or out-paralogs. The method is illustrated and validated by extensive genomic analyses. The performances of the overall approach are characterized in global terms for three sets of species (Chlamydiae, Mycobacteria, Aspergilli), showing that at least 75% of the sets of orthologs contain at most one protein from a given species. The sets including more than one protein from a given species are shown to contain in-paralogs in proportions varying from 28% to 58%. The characterizations also show that the large majority of SPOs are associated with ancestral motifs, and accordingly not prone to chaining effects that might be triggered by multi-domain proteins. Further the SPO formulation is compared to other similarity based ortholog detection methods. Beyond core common results, significant differences are observed between various methods, which can be accounted for to a large extent on conceptual grounds, relative to the different merging schemes involved. Such comparisons highlight a major advantage of the SPO approach concerning the proper clustering of associated paralogs, which appear to be often dispatched spuriously into distinct orthologous classes. Finally the perspectives for future applications and elaborations of SPO-based compositional analyses are discussed. PMID- 22056700 TI - [Morbidity and mortality conferences: should quality be favored over quantity?]. PMID- 22056701 TI - Differential expression of MMP-2, MMP-9 and PCNA in endometriosis and endometrial carcinoma. AB - OBJECTIVES: Endometriosis is a common gynaecological disease with clinical symptoms such as chronic pain, infertility and intra-abdominal adhesions. Different theories on the pathogenesis of endometriosis and especially its aggressive subtype with infiltrative growth have been discussed. The objective of this study is to evaluate differences in proliferation and invasive properties of invasive colorectal endometriosis, superficial peritoneal endometriosis and endometrial carcinoma (G1 and G2). STUDY DESIGN: Paraffin embedded tissues of peritoneal endometriosis, endometriosis of the intestine and endometrial carcinoma from 97 patients were stained immunohistochemically to assess differences in expression patterns of matrix metalloproteinases (MMP-2, MMP-9) as markers of invasion and the marker of proliferation PCNA. MMP expression was evaluated using the Immuno Reactive Score (IRS) (combining positive cell ratio and staining intensity) and PCNA expression was assessed as the percentage of positively stained cells in representative areas. RESULTS: MMP-2, MMP-9 and PCNA showed differential expression patterns in the different tissues examined. MMP-2 and PCNA expression was stronger in invasive colorectal endometriosis than in superficial peritoneal endometriosis (p=0.0394). MMP-9, however, was more frequently expressed in peritoneal endometriosis (59.1%) than in colorectal endometriosis (44.4%). This result did not reach statistical significance. When colorectal endometriosis was compared to low grade endometrial carcinoma, proliferation detected by PCNA was significantly higher in endometriosis (p=0.0008). MMP-2 and MMP-9 showed higher expression in endometrial carcinoma than in endometriosis. CONCLUSIONS: There are obvious differences in expression patterns of MMP-2, MMP-9 and PCNA in different stages of endometriosis and in endometrial cancer. These markers can be helpful to evaluate aggressiveness and invasiveness of endometriosis in different localizations. The results obtained could be of relevance for a better understanding of the pathogenesis of endometriosis and the development of an individual therapy concept. PMID- 22056702 TI - [Proposal of novel staging and grading system of primary biliary cirrhosis]. PMID- 22056703 TI - [Present status and future prospect of autoimmune hepatitis]. PMID- 22056704 TI - [The significance of scoring systems in the diagnosis of autoimmune hepatitis]. PMID- 22056705 TI - [Autoimmune hepatitis with overlapping features of primary biliary cirrhosis]. PMID- 22056706 TI - [Management of patients with glucocorticoid-resistant autoimmune hepatitis]. PMID- 22056707 TI - [Clinical courses and pregnancy outcomes in Japanese women with inflammatory bowel disease]. AB - In this study, we analyzed the clinical courses and the pregnancy outcomes in Japanese women with inflammatory bowel disease (IBD) in our hospital in the recent 10 years. We analyzed 49 pregnancies in 38 patients with ulcerative colitis (UC) and 24 pregnancies in 16 patients with Crohn's disease (CD) retrospectively. The results indicated that pregnancy has less influence on the clinical courses of IBD and that IBD also has less influence on the pregnancy outcomes. However, we should pay attention to the results that the patients with CD tend to deteriorate if conception occurs when CD is active and that patients with active UC tend to have more adverse pregnancy outcomes than patients in remission. In conclusion, patients with IBD are recommended to become pregnant when the diseases are in remission and treatment using selected safe medications should be continued during the pregnancy. PMID- 22056708 TI - [Transcatheter arterial chemotherapy with miriplatin for patients with hepatocellular carcinoma and chronic renal failure]. AB - Miriplatin is a novel lipophilic platinum complex developed to treat hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting chronic renal failure, there is no reliable data regarding clinical toxicity of miriplatin in HCC patients with chronic renal failure. We retrospectively evaluated the safety and efficacy of transcatheter arterial chemotherapy with miriplatin in 67 HCC patients with chronic renal failure (estimated glomerular filtration rate [GFR] by the Cockcroft-Gault equation <60ml/min). Estimated GFR within 2 months after miriplatin administration did not decrease significantly by the Wilcoxon signed rank test (pretreatment;46ml/min, 1 month;48ml/min;P=0.019, 2 months;45ml/min;P=0.619 [P<0.003 was significant by the Bonferroni correction]). Complete response in terms of tumor necrosis was achieved in 14 of 67 patients and no serious adverse events were observed. These results suggested that transcatheter arterial chemotherapy with miriplatin can be used safely for HCC patients with chronic renal failure. PMID- 22056709 TI - [A very elderly case of advanced gastric cancer with disseminated carcinomatosis of bone marrow and multiple bone metastasis, diagnosed by extremely elevated serum alkaline phosphatase levels, and treated with low-dose S-1 to avoid disseminated intravascular coagulation]. AB - We report an 87-year-old woman who was admitted to our hospital due to anemia and extremely elevated serum alkaline phosphatase (ALP) levels. We diagnosed advanced gastric cancer with disseminated carcinomatosis of the bone marrow and multiple bone metastasis. She was immediately treated with low-dose S-1 (50mg/body, p.o., days 1-14) and zoledronic acid hydrate (4mg/body, i.v., day 1) to avoid disseminated intravascular coagulation (DIC). After 1 course of the treatment, she could completely avoid DIC and we found the primary lesion and the metastasis had decreased. Now she is an outpatient and continues treatment without relapse for about 6 months. We consider low-dose S-1 and zoledronic acid hydrate combination therapy to be an effective strategy against advanced gastric cancer with disseminated carcinomatosis of the bone marrow and multiple bone metastasis in very elderly cases. PMID- 22056710 TI - [A case of gastrointestinal stromal tumor of the duodenum with a huge abscess]. AB - A 36-year-old man admitted for upper abdominal pain and fever. Enhanced abdominal computed tomography showed a cystic tumor with an air fluid level, measuring 140mm in size, along the side of the first and second portions of the duodenum. The common bile duct, portal vein, and proper hepatic artery were displaced by the tumor. Upper gastrointestinal endoscopy showed duodenal ulcer, but fistula was not confirmed. Combining all imaging and clinical findings, it was clinically diagnosed as duodenal submucosal tumor with abscess, and elective surgery was performed. There was a huge mass in the Morrison pouch, with severe adhesion to the second portion of the duodenum, gall bladder, common bile duct, and transverse colon. Subtotal stomach-preserving pancreaticoduodenectomy with transverse colectomy was performed. A fistula from the second portion of the duodenum to the tumor was confirmed on the resected specimen. Histological examination showed gastrointestinal stromal tumor originating in the duodenum. PMID- 22056711 TI - [Effectiveness of systemic chemotherapy of GEM+CBDCA+5-FU/LV and hepatic arterial infusion of CDDP in a case of advanced, combined hepatocellular cholangiocarcinoma with multiple lung metastases]. AB - This patient is a male in his 30's. He was diagnosed as hepatitis B virus-related huge primary liver cancer, 10cm in diameter, located in segment 4, accompanied with left portal thrombus and multiple lung metastases. Ten months after repeating systemic chemotherapy using gemcitabine (GEM)+carboplatin (CBDCA)+5 FU/leucovorin (LV) and hepatic arterial infusion chemotherapy with cisplatin (CDDP) 4 times, extended left lobectomy with caudate lobe could be successfully performed because of marked reducion of the huge tumor. The pathology revealed almost entirely necrotic changes of the main tumor, and the remaining, viable tumor nests showed combined hepatocellular and cholangiocarcinoma. Systemic chemotherapy was repeatedly given afterwards, which kept the pulmonary metastases stable without growth. The present case suggests that systemic chemotherapy using GEM+CBDCA+5-FU/LV may be useful in the multimodal treatment for the combined hepatocellular and cholangiocarcinoma with distant metastases. PMID- 22056712 TI - [A case of spontaneous complete necrosis of hepatocellular carcinoma sized 10cm in diameter demonstrated by the resected specimen]. AB - A 68-year-old man with chronic hepatitis C and of a heavy drinker was admitted to our hospital because of a huge liver tumor (10cm in diameter) in segment-5 detected on CT in July 2009. One month later, the size of liver tumor was reduced to 5cm in diameter and another liver tumor of 1cm in segment-3 was detected on CT. AFP and AFP-L3 spontaneously decreased to normal range. In October, a partial hepatectomy was performed. The resected specimen demonstrated complete necrosis with thick capsule. The tumor in segment-3 became equivocal without resection. We considered this is a case of spontaneous complete necrosis of hepatocellular carcinoma. PMID- 22056713 TI - [A resected case of metachronous liver metastasis from mixed adenoneuroendocrine carcinoma of the stomach]. AB - A 71-year-old woman was found in gastroendoscopic examination to have a type 2 tumor at the posterior wall of the stomach with two type 0-IIa early adenocarcinomas at the lesser curvature and anterior wall. She underwent distal gastrectomy. Pathological evaluation of the type 2 tumor was mixed adenoneuroendocrine carcinoma and that of two type 0-IIa tumors were well differentiated tubular adenocarcinomas. The solitary metastasis was found in liver S8 on 15th month though S-1 was taken after the operation. Partial resection of the liver was performed, and its histological findings were similar to the mixed adenoneuroendocrine carcinoma of the stomach. After adjuvant chemotherapy with S-1+CPT-11 during half a year, S-1 single therapy was done for 16 months, and there is no evidence of recurrence for 28 months after liver resection. PMID- 22056714 TI - [A case of unilocular serous cystic neoplasm mimicking mucinous cystic neoplasm]. AB - A 40's woman had a cystic lesion in the tail of the pancreas that had grown over a 1.5-year period. Endoscopic ultrasound revealed a partition structure and "cyst in-cyst" like lesion, and a diagnosis of mucinous cystic neoplasm was made. The patient underwent distal pancreatectomy with splenectomy. Following histological examination, our final diagnosis was revised to unilocular serous cystic neoplasm since the increase in cysts was due to hemorrhage and the partition structure was in fact granulation tissue. We here discuss this rare case with reference to previous published reports. PMID- 22056716 TI - Toward in silico structure-based ADMET prediction in drug discovery. AB - Quantitative structure-activity relationship (QSAR) methods and related approaches have been used to investigate the molecular features that influence the absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs. As the three-dimensional structures of several major ADMET proteins become available, structure-based (docking-scoring) computations can be carried out to complement or to go beyond QSAR studies. Applying docking-scoring methods to ADMET proteins is a challenging process because they usually have a large and flexible binding cavity; however, promising results relating to metabolizing enzymes have been reported. After reviewing current trends in the field we applied structure-based methods in the context of receptor flexibility in a case study involving the phase II metabolizing sulfotransferases. Overall, the explored concepts and results suggested that structure-based ADMET profiling will probably join the mainstream during the coming years. PMID- 22056715 TI - Classification of scaffold-hopping approaches. AB - The general goal of drug discovery is to identify novel compounds that are active against a preselected biological target with acceptable pharmacological properties defined by marketed drugs. Scaffold hopping has been widely applied by medicinal chemists to discover equipotent compounds with novel backbones that have improved properties. In this article we classify scaffold hopping into four major categories, namely heterocycle replacements, ring opening or closure, peptidomimetics and topology-based hopping. We review the structural diversity of original and final scaffolds with respect to each category. We discuss the advantages and limitations of small, medium and large-step scaffold hopping. Finally, we summarize software that is frequently used to facilitate different kinds of scaffold-hopping methods. PMID- 22056717 TI - An updated meta-analysis of methylenetetrahydrofolate reductase gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy. AB - Studies investigating the association of methylenetetrahydrofolate reductase (MTHFR) gene 677C/T polymorphism with diabetic nephropathy and diabetic retinopathy have so far reported inconclusive results. We therefore aim to address this inconclusiveness by conducting a meta-analysis. Random-effects model was applied irrespective of between-study heterogeneity. Data and study quality were assessed in duplicate. A total of 7807 and 1599 subjects from 21 and 8 studies were analyzed for diabetic nephropathy and diabetic retinopathy, respectively. Carriers of 677TT genotype were 1.71 (95% confidence interval [95% CI]: 1.02-2.88; P=0.042) and 2.89 (95% CI: 1.51-5.53; P=0.001) times more likely to develop diabetic nephropathy separately relative to diabetic patients without nephropathy and nondiabetic controls. Likewise, this association was preserved for diabetic patients with retinopathy referring to those without (odds ratio [OR]=1.86; 95% CI: 1.21-2.86; P=0.004). Subgroup analyses showed that ethnicity was a possible confounder, especially in West Asians and Africans, and so were gender and duration of diabetes mellitus in diabetic nephropathy studies. Probability of publication bias was low across all comparisons as reflected by the funnel plot and corresponding test. Taken together, our results demonstrate that MTHFR gene 677TT genotype might confer a moderately augmented risk for diabetic nephropathy and diabetic retinopathy. PMID- 22056718 TI - Glycated hemoglobin in ST-elevation myocardial infarction without previously known diabetes: its short and long term prognostic role. AB - In 518 consecutive STEMI non-diabetic patients, glycated hemoglobin>6.5% was not associated with increased short and long term mortality, but was associated with higher admission glucose values, worse in-hospital glycemic control and a higher incidence of acute insulin resistance (HOMA index). PMID- 22056719 TI - The glycemic triumvirate and diabetic complications: is the whole greater than the sum of its component parts? AB - The dysglycemia of diabetes mellitus can be depicted as the glycemic triumvirate with its 3 main components: the sustained chronic (ambient) hyperglycemia, glucose variability and hypoglycemic episodes. The respective contributions of these glycemic disorders to the overall risk for diabetic complications remain a subject of debate. At present, there is cogent evidence for the direct deleterious effect of ambient hyperglycemia while the roles exerted by glucose variability and hypoglycemia remain less documented and only based on observational and pathophysiological studies. In addition, these 3 glycemic disorders could be regarded as components of either an additive or an initiator/accelerator model according to whether each disorder exerts an independent or inter-dependent effect on the development and progression of diabetes-related complications, respectively. In the present review, pros and cons arguments for each model are debated. However it is highly likely that these 3 glycemic disorders have both direct (spoke in a wheel) and indirect (link in a chain) causal effects on clinical cardiovascular outcomes. As a consequence, the relationship between the so-called glycemic triumvirate and diabetic complications might be summarized by the famous Aristotle's aphorism: "the whole is greater than the sum of its parts". PMID- 22056720 TI - The 3C study: coverage cost and care of type 1 diabetes in China--study design and implementation. AB - AIM: To describe coverage, cost and care of type 1 diabetes (T1D) in 2 regions of China--Beijing and Shantou--including: METHODS: This is a mixed-methods descriptive study with three arms--coverage, cost and care. It is taking place in 4 tertiary hospitals, 3 secondary hospitals and 4 primary health facilities in Beijing, and 2 tertiary hospitals, 2 secondary hospitals and 2 primary health centres in Shantou, China. Two additional hospitals are involved in the coverage arm of the study. T1D participants are recruited from a 3-year list generated by each hospital and from those attending the outpatient clinic or admitted to the inpatient ward. Participants also include health care professionals and government officials. To determine coverage of care, a list of people with T1D is being developed including information on diagnosis, age, sex and vital status. The age and sex distribution will be compared with the expected distribution. To estimate the economic burden of T1D three groups of costs will be calculated - direct medical costs, direct non-medical costs and indirect costs from different perspectives of analysis (patients and their families, health system, insurer and societal perspective). The data are being collected from people with T1D (patient parents face-to-face interviews), hospital billing departments, medical records and government officials using a combined "top-down, bottom-up" approach developed to validate the data. Quality of life is assessed using the EQ-5D tool and burden of disease is measured based on clinical outcomes and complications. Standard care will be defined, costed and compared to the cost of current care identified within the study to determine the investment required to improve outcomes. The third arm includes three components - health policy, clinical care and education, and information management. Face-to-face, semi-structured interviews are conducted with people with T1D (for those <15 years of age parents are interviewed), health care professionals, senior hospital management and government officials. The core Summary of Diabetes Self-Care Activities Measure plus an additional 6 questions from the revised SDSCA scale are used to assess patient self-care. A medical records audit tool is used to assess care [7]. Clinical outcomes and self-care activities will be analysed for associations with care and education. Information management and care processes will be described using the Standard for Integration Definition for Function Modelling (IDEF0) [8]. PROGRESS TO DATE: At the time of writing (early October) the 3-year case list includes 1269 people with type 1 diabetes from Beijing and 481 people for Shantou, a total of 1750. In addition, two hundred and twenty people with T1D or their parents participated in face-to-face interviews in Beijing and 183 in Shantou, a total of 403. PRACTICAL PRELIMINARY CONCLUSIONS: Key implementation considerations were identified early in the project. Project success is dependent on strong local partnerships with local opinion leaders and key officials. It is important that a physician is the first point of contact to build the case list and recruit participants. July, August and January are peak months for recruiting school-age children in the Children's Hospital as this is school vacation period when they are more likely to attend clinics. PMID- 22056721 TI - Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8. AB - BACKGROUND: Adenosine triphosphate (ATP)-sensitive potassium cardiac channels consist of inward-rectifying channel subunits Kir6.1 or Kir6.2 (encoded by KCNJ8 or KCNJ11) and the sulfonylurea receptor subunits SUR2A (encoded by ABCC9). OBJECTIVE: To examine the association of mutations in KCNJ8 with Brugada syndrome (BrS) and early repolarization syndrome (ERS) and to elucidate the mechanism underlying the gain of function of ATP-sensitive potassium channel current. METHODS: Direct sequencing of KCNJ8 and other candidate genes was performed on 204 BrS and ERS probands and family members. Whole-cell and inside-out patch clamp methods were used to study mutated channels expressed in TSA201 cells. RESULTS: The same missense mutation, p.Ser422Leu (c.1265C>T) in KCNJ8, was identified in 3 BrS and 1 ERS probands but was absent in 430 alleles from ethnically matched healthy controls. Additional genetic variants included CACNB2b D601E. Whole-cell patch-clamp studies showed a 2-fold gain of function of glibenclamide-sensitive ATP-sensitive potassium channel current when KCNJ8-S422L was coexpressed with SUR2A-wild type. Inside-out patch-clamp evaluation yielded a significantly greater half maximal inhibitory concentration for ATP in the mutant channels (785.5 +/- 2 vs 38.4 +/- 3 MUM; n = 5; P <.01), pointing to incomplete closing of the ATP-sensitive potassium channels under normoxic conditions. Patients with a CACNB2b-D601E polymorphism displayed longer QT/corrected QT intervals, likely owing to their effect to induce an increase in L-type calcium channel current (I(Ca-L)). CONCLUSIONS: Our results support the hypothesis that KCNJ8 is a susceptibility gene for BrS and ERS and point to S422L as a possible hotspot mutation. Our findings suggest that the S422L-induced gain of function in ATP-sensitive potassium channel current is due to reduced sensitivity to intracellular ATP. PMID- 22056722 TI - Cardiac device infections are associated with a significant mortality risk. AB - BACKGROUND: Cardiac device infections (CDIs) are a serious complication associated with the implantation of cardiac rhythm devices. However, the effect of CDI on the subsequent risk of mortality is unknown. OBJECTIVE: To assess the prognostic importance of CDI in recipients of implantable cardioverter defibrillator and cardiac resynchronization therapy - defibrillator. METHODS: All patients who received their initial implantable cardioverter defibrillator/cardiac resynchronization therapy - defibrillator between January 2000 and September 2009 were included. During follow-up, the occurrence of CDI and all-cause mortality were noted. The prognostic importance of the first CDI on mortality was assessed by modeling CDI as a time-dependent covariate in the Cox proportional hazards model. RESULTS: A total of 2476 patients (79% men; mean age 62 +/- 13 years) were included in this analysis. During follow-up, CDI occurred in 64 (2.6%) patients. The 1-year mortality following first CDI was 16.9% (95% confidence interval 6.7%-27.1%). Experiencing the first CDI was associated with a 1.9-fold (hazard ratio 1.87; 95% confidence interval 1.07-3.26) increased risk of mortality compared to patients who did not experience CDI. After controlling for possible confounders, this increased to a 2.4-fold (hazard ratio 2.40; 95% confidence interval 1.35-4.28) increased risk of mortality. CONCLUSIONS: In a large cohort of patients who receive implantable cardioverter defibrillator/cardiac resynchronization therapy - defibrillator after their initial implant, the 3-year incidence of CDI was 2.6%. The occurrence of CDI was associated with substantial 1-year mortality, and patients experiencing CDI had a more than 2-fold increased risk of mortality compared with patients who remained free from CDI. PMID- 22056723 TI - Three-dimensional visualization of the entire reentrant circuit of bundle branch reentrant tachycardia. PMID- 22056724 TI - Formation of droplet networks that function in aqueous environments. AB - Aqueous droplets in oil that are coated with lipid monolayers and joined through interface bilayers are useful for biophysical measurements on membrane proteins. Functional networks of droplets that can act as light sensors, batteries and electrical components can also be made by incorporating pumps, channels and pores into the bilayers. These networks of droplets mimic simple tissues, but so far have not been used in physiological environments because they have been constrained to a bulk oil phase. Here, we form structures called multisomes in which networks of aqueous droplets with defined compositions are encapsulated within small drops of oil in water. The encapsulated droplets adhere to one another and to the surface of the oil drop to form interface bilayers that allow them to communicate with each other and with the surrounding aqueous environment through membrane pores. The contents in the droplets can be released by changing the pH or temperature of the surrounding solution. The multicompartment framework of multisomes mimics a tissue and has potential applications in synthetic biology and medicine. PMID- 22056725 TI - Signalling of DNA damage and cytokines across cell barriers exposed to nanoparticles depends on barrier thickness. AB - The use of nanoparticles in medicine is ever increasing, and it is important to understand their targeted and non-targeted effects. We have previously shown that nanoparticles can cause DNA damage to cells cultured below a cellular barrier without crossing this barrier. Here, we show that this indirect DNA damage depends on the thickness of the cellular barrier, and it is mediated by signalling through gap junction proteins following the generation of mitochondrial free radicals. Indirect damage was seen across both trophoblast and corneal barriers. Signalling, including cytokine release, occurred only across bilayer and multilayer barriers, but not across monolayer barriers. Indirect toxicity was also observed in mice and using ex vivo explants of the human placenta. If the importance of barrier thickness in signalling is a general feature for all types of barriers, our results may offer a principle with which to limit the adverse effects of nanoparticle exposure and offer new therapeutic approaches. PMID- 22056726 TI - Challenges and opportunities for structural DNA nanotechnology. AB - DNA molecules have been used to build a variety of nanoscale structures and devices over the past 30 years, and potential applications have begun to emerge. But the development of more advanced structures and applications will require a number of issues to be addressed, the most significant of which are the high cost of DNA and the high error rate of self-assembly. Here we examine the technical challenges in the field of structural DNA nanotechnology and outline some of the promising applications that could be developed if these hurdles can be overcome. In particular, we highlight the potential use of DNA nanostructures in molecular and cellular biophysics, as biomimetic systems, in energy transfer and photonics, and in diagnostics and therapeutics for human health. PMID- 22056727 TI - Nanoparticles: Barrier thickness matters. PMID- 22056728 TI - Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population. AB - Nanoparticles are considered a primary vehicle for targeted therapies because they can pass biological barriers and enter and distribute within cells by energy dependent pathways. So far, most studies have shown that nanoparticle properties, such as size and surface, can influence how cells internalize nanoparticles. Here, we show that uptake of nanoparticles by cells is also influenced by their cell cycle phase. Although cells in different phases of the cell cycle were found to internalize nanoparticles at similar rates, after 24 h the concentration of nanoparticles in the cells could be ranked according to the different phases: G2/M > S > G0/G1. Nanoparticles that are internalized by cells are not exported from cells but are split between daughter cells when the parent cell divides. Our results suggest that future studies on nanoparticle uptake should consider the cell cycle, because, in a cell population, the dose of internalized nanoparticles in each cell varies as the cell advances through the cell cycle. PMID- 22056729 TI - Bionanoscience: Nanoparticles in the life of a cell. PMID- 22056730 TI - Thermal-gradient-induced interaction energy ramp and actuation of relative axial motion in short-sleeved double-walled carbon nanotubes. AB - We investigate the phenomenon of actuation of relative linear motion in double walled carbon nanotubes (DWNTs) resulting from a temperature gradient. Molecular dynamics simulations of DWNTs with short outer tube reveal that the outer tube is driven towards the cold end of the long inner tube. It is also found that the terminal velocity of the sleeve roughly depends linearly on the applied thermal gradient. We calculate the inter-tube interaction energy surface which is revealed to have a gradient depending upon the applied thermal gradient. Consequently, it is proposed that the origin of the thermophoretic motion of the outer tube may be attributed partially to the existence of such an energy gradient. A simple analytical model is presented accounting for the gradient in energy profile as well as the effect of biased thermal noise. It is shown that the proposed model predicts the dynamical behaviour of the long-time performance reasonably well. PMID- 22056731 TI - Epidemiology of community-acquired pneumonia in children of Latin America and the Caribbean: a systematic review and meta-analysis. AB - BACKGROUND: This systematic review evaluated the incidence, etiology, and use of resources in bacterial, non-tuberculosis community-acquired pneumonia (CAP) in immune-competent children aged <5 years. METHODS: Systematic searches (1980-2008) were performed using MEDLINE, Cochrane Library, EMBASE, LILACS, generic, and academic Internet searches. Regional health ministries, the Pan American Health Organization (PAHO), regional proceedings, doctoral theses, and the reference lists of included studies were also searched, and experts were consulted. Arcsine transformations and the DerSimonian-Laird random-effects model were used for proportion meta-analyses. RESULTS: The search yielded 1220 references; 60 were included in the meta-analysis, giving a total 23 854 CAP episodes with an incidence of 919/100 000 child-years in children aged <5 years. Streptococcus pneumoniae was the most frequently isolated agent (11.08%; 95% confidence interval (CI) 7.63-15.08), and pneumococcal serotype 14 was most prevalent (33.00%; 95% CI 25.95-40.45). Other common agents were Haemophilus influenzae and Mycoplasma pneumoniae. Health economics data on CAP in the region were scarce. About one-fourth of CAP patients required hospitalization (median length of stay 11 days, range 5-13.5 days). CONCLUSIONS: The burden of CAP was substantial, with S. pneumoniae, H. influenzae, and M. pneumoniae being the most common pathogens identified. High quality primary studies on disease incidence, use of health resources, and standardized data collection on disease burden and circulating strains are essential to provide baseline data for the future evaluation of vaccine impact. PMID- 22056732 TI - Lymphatic preservation in varicocele in the adolescent: does prior embolization limit spermatic dissection? AB - OBJECTIVE: One of the complications after complete section of the spermatic pedicle in the treatment of adolescent idiopathic varicocele is the formation of a scrotal lymphocele. This can be avoided by preserving lymphatic vessels using dye, but there is a risk that dissection may be complicated in patients who have previously undergone embolization. The aim of this study was to determine whether prior embolization limits spermatic dissection. MATERIAL AND METHOD: We used lymphography with dye (Patent Blue) prior to surgery in order to mark and preserve the lymph vessels during spermatic section. This was done by laparoscopy with a single umbilical port. RESULTS: We treated six patients aged 12.5-15 years (mean 13.12 years), two of whom had grade 2 varicoceles and four grade 3. Prior percutaneous embolization with metallic coils had been undertaken in all cases but had not been curative. Post-surgery controls were undertaken for a mean duration of 5 months without any lymphoceles appearing. No testicles were lost, nor did any other complication arise. CONCLUSION: The presence of embolization material in the spermatic veins and perivascular fibrosis does not complicate surgery, enabling the single port laparoscopic technique to be undertaken. PMID- 22056733 TI - Influences of composite-composite join on light transmission characteristics of layered resin composites. AB - OBJECTIVES: The purposes of this study were: (1) to determine the light transmission characteristics (straight-line and diffusion transmission) of bulk filled and layered resin composites, and (2) to evaluate the effect of layering filling on translucency and color appearance of resin composites. METHODS: Three light-cured resin composites (EsteliteSigma, Tokuyama Dental; Beautifil II, Shofu and Clearfil Majesty, Kuraray Medical) in A2 and OA2 shades were used in this study. 2 mm-thick resin composite discs were prepared by two methods; bulk filling technique (2 mm filling at one time), layering technique (two layers each 1 mm thickness). The transmitted light intensity of each resin composite disc was measured using a goniophotometer, and diffusion factor (DF), an indicator for diffuse transmission property, and peak gain (G0) for straight-line transmission were calculated from the light distribution graphs. Color was measured according to the CIELAB color scale on a spectrophotometer, and the translucency parameter (TP) and color difference (DeltaE(*)) between bulk-filled and layered specimens were calculated. The data were statistically analyzed using three-way ANOVA, and Dunnett's T3 and t-test for post-hoc test. RESULTS: Three-way ANOVA revealed that the layered specimens had significantly lower G0 values and higher DF values than the bulk-filled specimens, and significantly reduced TP values. The color differences (DeltaE(*)) ranged from 1.07 to 1.85 between the bulk-filled and layered specimens. SIGNIFICANCE: Resin composite placed in layers exhibited reduced straight-line light transmission and increased diffusion transmission compared with bulk-filled resin composite. The layering technique affected the translucency and color rendition of resin composite. PMID- 22056734 TI - Tetramethylenedisulfotetramine intoxication presenting with de novo Status Epilepticus: a case series. AB - Tetramethylenedisulfotetramine (TETS), a neurotoxic rodenticide banned in China, has repeatedly been shown to kill healthy people. We report a series of nine people with TETS intoxication presenting with Convulsive Status Epilepticus (CSE) as the initial manifestation. Median duration of CSE after admission was 6h. All had normal neuro-imaging but inter-ictal EEG showed bilateral epileptic waves. Despite aggressive anti-convulsive treatment, attempts at reducing TETS levels and supportive therapy, outcomes were poor. Multiple organ dysfunction syndrome (MODS) occurred in six people, of whom three died. TETS exposure should be part of the differential diagnosis in people presenting with unexplained SE in rural China, particularly if this occurs in family clusters. Over 14,000 cases of TETS intoxication occurred in China between 1 January 1991 and 31 December 2010, and 932 of these died. Cases were widely distributed throughout the country, occurring primarily in rural areas. CSE seems to be a frequent symptom of severe intoxication. There is, however, still a lack of information about the hazards of TETS and it is imperative that both the public and physicians are made aware of its risks and complications. PMID- 22056736 TI - Developments in obesity genetics in the era of genome-wide association studies. AB - Obesity is an important factor contributing to the global burden of morbidity and mortality. By identifying obesity susceptibility genes, scientists aim to elucidate some of its aetiology. Early studies used candidate gene and genome wide linkage approaches to search for such genes with limited success. However, the advent of genome-wide association studies (GWAS) has dramatically increased the pace of gene discovery. So far, GWAS have identified at least 50 loci robustly associated with body mass index (BMI), waist-to-hip ratio, body fat percentage and extreme obesity. Some of these have been shown to replicate in non white populations and in children and adolescents. Furthermore, for some loci interaction studies have shown that the BMI-increasing effect is attenuated in physically active individuals. Despite many successful discoveries, the effect sizes of the established loci are small, and combined they explain only a fraction of the inter-individual variation in BMI. The low predictive value means that their value in mainstream health care is limited. However, as most of these newly established loci were not previously linked to obesity, they may provide new insights into body weight regulation. Continued efforts in gene discovery, using a range of approaches, will be needed to increase our understanding of obesity. PMID- 22056737 TI - Ruling out IBD: estimation of the possible economic effects of pre-endoscopic screening with F-calprotectin. AB - OBJECTIVES: To estimate the possible economic effects of a sequential testing strategy with F-calprotectin to minimize colonoscopies. DESIGN AND METHODS: Retrospective study in a third party payer perspective. The costs were calculated from initial F-calprotectin test results of 3639 patients. Two cut-off levels were used: 50 MUg/g feces and 100 MUg/g feces, respectively. The cost effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for colonoscopies. RESULTS: The estimated demand for colonoscopies was reduced by 50% with the 50 MUg/g cut-off and 67% with the 100 MUg/g cut-off. This corresponded to a cost avoidance of approximately ?1.57 million and ?2.13 million, respectively. CONCLUSIONS: The use of F-calprotectin as a screening test substantially could reduce the number of invasive measurements necessary in the diagnostic work-up of patients with suspected IBD, as well as the associated costs. PMID- 22056738 TI - Fatty liver index as an indicator of metabolic syndrome. AB - OBJECTIVE: The aim of this study was to find an early indicator of metabolic syndrome (MetS). DESIGN AND METHODS: We measured several anthropometric, biochemical, haematological, and oxidative damage parameters in 128 middle-aged Caucasian men divided into two groups: patients with MetS (n=69) and healthy controls (n=59), and used Weka REPTree and SimpleCART algorithms to identify the most reliable predictor of MetS. RESULTS: Oxidative damage parameters did not differ between the groups, suggesting that oxidative damage is less prominent at the early stage of MetS. The algorithms singled out fatty liver index (FLI) as the best variable for discriminating between healthy and MetS subjects. This finding was confirmed by the receiver-operating characteristic (ROC) curve analysis, which set FLI 68.53 as the threshold value for MetS diagnosis. CONCLUSIONS: FLI is the most reliable tool for diagnosing MetS. The absence of oxidative damage does not rule out oxidative stress but may indicate that MetS is at an early stage. PMID- 22056739 TI - Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. AB - BACKGROUND: Concurrent chemoradiotherapy (CCRT) has been shown to improve outcomes for stage III-IV nasopharyngeal carcinoma (NPC) patients compared with radiotherapy (RT) alone, but the effectiveness of the combined therapy for stage II NPC patients is unknown. METHODS: Patients with Chinese 1992 stage II NPC were randomly assigned to receive either RT alone (n = 114) or CCRT (n = 116). The CCRT patients were given concurrent cisplatin (30 mg/m(2) on day 1) weekly during RT. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), distant metastasis-free survival, and locoregional relapse-free survival. All patients were analyzed by the intent-to treat principle. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) and in multivariable analyses to test the independent statistical significance of treatment intervention. Toxic effects and the response to treatment were analyzed using the chi(2) test. All statistical tests were two-sided. RESULTS: With a median follow-up of 60 months, adding chemotherapy statistically significantly improved the 5-year OS rate (94.5% vs 85.8%; HR of death = 0.30, 95% CI = 0.12 to 0.76; P = .007), PFS (87.9% vs 77.8%; HR of progression = 0.45, 95% CI = 0.23 to 0.88; P = .017), and distant metastasis-free survival (94.8% vs 83.9%; HR of distant relapse = 0.27, 95% CI = 0.10 to 0.74; P = .007); however, there was no statistically significant difference in the 5-year locoregional relapse-free survival rate (93.0% vs 91.1%; HR of locoregional relapse = 0.61, 95% CI = 0.25 to 1.51; P = .29). Multivariable analysis showed that the number of chemotherapy cycles was the only independent factor that was associated with OS, PFS, and distant control in stage II NPC. The CCRT arm experienced statistically significantly more acute toxic effects (P = .001), although the rate of late toxic effects did not increase statistically significantly. CONCLUSION: Concurrent chemotherapy and radiotherapy is associated with a considerable survival benefit for patients with stage II NPC. PMID- 22056741 TI - Estimation of risk for the general public contaminated with radioiodine in nuclear accidents from the viewpoint of nuclear medicine physicians. PMID- 22056740 TI - Age-related changes in mouse taste bud morphology, hormone expression, and taste responsivity. AB - Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2 and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact. PMID- 22056742 TI - Benzobistriazinones and related heterocyclic ring systems as potent, orally bioavailable positive allosteric AMPA receptor modulators. AB - AMPA receptors (AMPARs) are an important therapeutic target in the CNS. A series of substituted benzobistriazinone, benzobispyrimidinone and related derivatives have been prepared with high potency and selectivity for the allosteric binding site of AMPARs. Further improvements have been made to previously reported series of positive AMPAR modulators and these compounds exhibit excellent in vivo activity and improved in vivo metabolic stability with up to 100% oral bioavailability in rat. PMID- 22056743 TI - Synthesis of sulfonamide-containing N-hydroxyindole-2-carboxylates as inhibitors of human lactate dehydrogenase-isoform 5. AB - N-Hydroxyindole-2-carboxylates possessing sulfonamide-substituents at either position 5 or 6 were designed and synthesized. The inhibitory activities of these compounds against isoforms 1 and 5 of human lactate dehydrogenase were analysed, and K(i) values of the most efficient inhibitors were determined by standard enzyme kinetic studies. Some of these compounds displayed state-of-the-art inhibitory potencies against isoform 5 (K(i) values as low as 5.6 MUM) and behaved as competitive inhibitors versus both the substrate and the cofactor. PMID- 22056744 TI - Benzisothiazolinone as a useful template for the design of new monoacylglycerol lipase inhibitors: investigation of the target residues and comparison with octhilinone. AB - The regulation of 2-arachidonoylglycerol (2-AG) levels is a major issue as 2-AG has been proven to participate in numerous physiopathological phenomena such as neuroprotection or analgesia. Octhilinone, a cysteine-reagent compound, has recently been shown to inhibit in the nanomolar range monoacylglycerol lipase (MAGL), the major enzyme responsible for the degradation of 2-AG. Here, we further investigate the mechanism by which octhilinone and its benzisothiazolinone analog inhibit human MAGL. We also provide new information on the structural requirements for MAGL inhibition by these compounds. Finally, we describe for N-octylbenzisothiazolinone a mode of inhibition which is partially different from that described for octhilinone, especially with regard to the targeted cysteine residues in the vicinity of the catalytic site. PMID- 22056745 TI - CoMFA and CoMSIA studies on fluorinated hexahydropyrimidine derivatives. AB - 3D-QSAR models of a series of fluorinated hexahydropyrimidine derivatives with cytotoxic activities have been developed using CoMFA and CoMSIA. These models provide a better understanding of the mechanism of action and structure-activity relationship of these compounds. By applying leave-one-out (LOO) cross validation study, the best predictive CoMFA model was achieved with 3 as the optimum number of components, which gave rise to a non-cross-validated r(2) value of 0.978, and standard error of estimate of 0.059, and F value of 144.492. Similarly, the best predictive CoMSIA model was derived with 4 as the number of components, r(2) value of 0.999, F value of 4381.143, and standard error of estimate, 0.011. The above models will inspire the design and synthesis of novel hexahydropyrimidines with enhanced potency and selectivity. PMID- 22056746 TI - Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity. AB - A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were optimized for cellular potency and kinase selectivity. This led to the identification of compound 24, BIX 02565, an attractive candidate for use in vitro and in vivo to explore the role of RSK as a target for the treatment heart failure. PMID- 22056747 TI - 3D-Quantitative structure-activity relationship and docking studies of the tachykinin NK3 receptor. AB - The tachykinin NK(3) receptor (NK(3)R) is a novel drug target for schizophrenia and drug abuse. Since few non-peptide antagonists of this G protein-coupled receptor are available, we have initiated this study to gain a better understanding of the structure-activity relationships of NK(3) antagonist compounds. We developed a 3D comparative molecular similarity index analysis (CoMSIA) model that gave cross-validated PLS values with q(2) >0.5 which were validated using a test set. We also describe the development of a homology model of the NK(3)R. The model was then used to develop a pharmacophore for docked ligands. This pharmacophore showed two aromatic, two hydrogen donor and one acceptor/aromatic points. These data will be useful for future structure-based drug discovery of ligands for the NK(3)R. PMID- 22056748 TI - Dose-dependent protective effect of ivabradine against ischemia-reperfusion induced renal injury in rats. AB - BACKGROUND/AIMS: This study was designed to investigate the dose-dependent protective effect of ivabradine, a specific inhibitor of the cardiac sinoatrial node, on renal ischemia-reperfusion (I/R) injury in rats. METHODS: Rats were divided into six groups: group 1, control; group 2, I/R (60 min ischemia followed by 24 h reperfusion); groups 3 and 4, 0.6-6 mg/kg ivabradine; and groups 5 and 6, sham+0.6-6 mg/kg ivabradine. At the end of the study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase contents were assayed in the kidney tissues; serum blood levels of urea nitrogen (BUN), creatinine (Cr) and albumin also were determined. RESULTS: Tissue MDA levels were found to be significantly higher in the I/R group, whereas SOD and CAT levels were lower when compared to the control group. Ivabradine (0.6 mg/kg) treatment reduced the MDA levels and elevated the SOD and CAT enzyme activity. Treatment with a dose of 6 mg/kg ivabradine further increased MDA levels and did not ameliorate SOD or CAT activities. Serum levels of BUN and Cr were significantly higher in the I/R group. I/R+0.6 mg ivabradine reduced the elevated BUN and Cr levels. CONCLUSION: This study indicates that ivabradine exerts a dose-dependent response beyond heart rate reduction against renal I/R injury. PMID- 22056749 TI - Decreased voluntary activity and amygdala levels of serotonin and dopamine in ovariectomized rats. AB - Estrogen is involved in numerous activities in the brain, such as learning, memory, fear, anxiety and mood. However, little is known about the pathways involved in the effects of estrogen in the brain. Therefore, to improve our understanding of the effects of estrogen, we examined the effects of ovariectomy (OVX)-a model of estrogen deficiency and menopause-on psychiatric functions, including voluntary activity. Female Wistar rats underwent OVX or sham operation. Voluntary momentum and circadian activity were monitored at 2 and 6 weeks, respectively. Rats also underwent microdialysis of the amygdala to determine serotonin (5-HT) and dopamine levels. Although the circadian rhythm was unchanged at 2 weeks, voluntary activity at 6 weeks was significantly lower in OVX rats than that in sham rats. This was due to significantly reduced voluntary activity in the 12-h dark phase, while no significant difference was detected in the 12-h light phase. Both 5-HT and dopamine levels in the amygdala were significantly lower in OVX rats than those in sham rats at 6 weeks after the procedure. In conclusion, these results indicate that estrogen is an important mediator of voluntary activity in rats, particularly during the dark phase. These effects of estrogen appear to involve reduced 5-HT and dopamine release in the amygdala. Further studies are needed to determine whether estrogen (and its deficiency) influences the synthesis, vesicular packaging, release, re-uptake and degradation of these transmitters. PMID- 22056750 TI - Differences in BTBR T+ tf/J and C57BL/6J mice on probabilistic reversal learning and stereotyped behaviors. AB - Autism spectrum disorders (ASD) represent a class of neurodevelopmental disorders characterized by impairments in social interaction, verbal and non-verbal communication, as well as restricted interests and repetitive behavior. This latter class of symptoms often includes features such as compulsive behaviors and resistance to change. The BTBR T+ tf/J mouse strain has been used as an animal model to investigate the social communication and restricted interest features in ASD. Less is known about whether this mouse strain models cognitive flexibility deficits also observed in ASD. The present experiment investigated performance of BTBR T+ tf/J and C57BL/6J on two different spatial reversal learning tests (100% accurate feedback and 80/20 probabilistic feedback), as well as marble burying and grooming behavior. BTBR T+ tf/J and C57BL/6J mice exhibited similar performance on acquisition and reversal learning with 100% accurate feedback. BTBR T+ tf/J mice were impaired in probabilistic reversal learning compared to that of C57BL/6J mice. BTBR T+ tf/J mice also displayed increased stereotyped repetitive behaviors compared to that of C57BL/6J mice as shown by increased marble burying and grooming behavior. The present findings indicate that BTBR T+ tf/J mice exhibit similar features related to "insistence on sameness" in ASD that include not only stereotyped repetitive behaviors, but also alterations in behavioral flexibility. Thus, BTBR T+ tf/J mice can serve as a model to understand the neural mechanisms underlying alterations in behavioral flexibility, as well as to test potential treatments in alleviating these symptoms. PMID- 22056751 TI - A voxel based morphometry study investigating brain structural changes in first episode psychosis. AB - Schizophrenia (SCZ) and bipolar disorder (BP) are associated with neuropathological brain changes, which are believed to disrupt connectivity between brain processes and may have common properties. Patients at first psychotic episode are unique, as one can assess brain alterations at illness inception, when many confounders are reduced or absent. SCZ (N=25) and BP (N=24) patients were recruited in a regional first episode psychosis MRI study. VBM methods were used to study gray matter (GM) and white matter (WM) differences between patient groups and case by case matched controls. For both groups, deficits identified are more discrete than those typically reported in later stages of illness. SCZ patients showed some evidence of GM loss in cortical areas but most notable were in limbic structures such as hippocampus, thalamus and striatum and cerebellum. Consistent with disturbed neural connectivity WM alterations were also observed in limbic structures, the corpus callosum and many subgyral and sublobar regions in the parietal, temporal and frontal lobes. BP patients displayed less evidence of volume changes overall, compared to normal healthy participants, but those changes observed were primarily in WM areas which overlapped with regions identified in SCZ, including thalamus and cerebellum and subgyral and sublobar sites. At first episode of psychosis there is evidence of a neuroanatomical overlap between SCZ and BP with respect to brain structural changes, consistent with disturbed neural connectivity. There are also important differences however in that SCZ displays more extensive structural alteration. PMID- 22056752 TI - Analysis of microsatellite mutations in buccal cells from a case-control study for lung cancer. AB - Exposure to tobacco carcinogens is the major cause of human lung cancer, but even heavy smokers have only about a 10% life-time risk of developing lung cancer. Currently used screening processes, based largely on age and exposure status, have proven to be of limited clinical utility in predicting cancer risk. More precise methods of assessing an individual's risk of developing lung cancer are needed. Because of their sensitivity to DNA damage, microsatellites are potentially useful for the assessment of somatic mutational load in normal cells. We assessed mutational load using hypermutable microsatellites in buccal cells obtained from lung carcinoma cases and controls to test if such a measure could be used to estimate lung cancer risk. There was no significant association between smoking status and mutation frequency with any of the markers tested. No significant association between case status and mutation frequency was observed. Age was significantly related to mutation frequency in the microsatellite marker D7S1482. These observations indicate that somatic mutational load, as measured using mutation frequency of microsatellites in buccal cells, increases with increasing age but that subjects who develop lung cancer have a similar mutational load as those who remain cancer free. This finding suggests that mutation frequency of microsatellite mutations in buccal cells may not be a promising biomarker for lung cancer risk. PMID- 22056753 TI - The mechanical stimulation of cells in 3D culture within a self-assembling peptide hydrogel. AB - The aim of this present study was to provide a scaffold as a tool for the investigation of the effect of mechanical stimulation on three-dimensionally cultured cells. For this purpose, we developed an artificial self-assembling peptide (SPG-178) hydrogel scaffold. The structural properties of the SPG-178 peptide were confirmed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and transmission electron microscopy (TEM). The mechanical properties of the SPG-178 hydrogel were studied using rheology measurements. The SPG-178 peptide was able to form a stable, transparent hydrogel in a neutral pH environment. In the SPG-178 hydrogel, mouse skeletal muscle cells proliferated successfully (increased by 12.4 +/- 1.5 times during 8 days of incubation; mean +/- SEM). When the scaffold was statically stretched, a rapid phosphorylation of ERK was observed (increased by 2.8 +/- 0.2 times; mean +/- SEM). These results demonstrated that the developed self-assembling peptide gel is non-cytotoxic and is a suitable tool for the investigation of the effect of mechanical stimulation on three-dimensional cell culture. PMID- 22056754 TI - Gold nanoparticles functionalized with therapeutic and targeted peptides for cancer treatment. AB - Functionalization of nanostructures such as gold nanoparticles (AuNPs) with different biological molecules has many applications in biomedical imaging, clinical diagnosis and therapy. Researchers mostly employed AuNPs larger than 10 nm for different biological and medicinal applications in previous studies. Herein, we synthesized a novel small (2 nm) AuNPs, which were functionalized with the therapeutic peptide, PMI (p12), and a targeted peptide, CRGDK for selective binding to neuropilin-1(Nrp-1) receptors which overexpressed on the cancer cells and regulated the process of membrane receptor-mediated internalization. It was found that CRGDK peptides increased intracellular uptake of AuNPs compared to other surface conjugations quantified by ICP-MS. Interestingly, CRGDK functionalized AuNPs resulted in maximal binding interaction between the CRGDK peptide and targeted Nrp-1 receptor overexpressed on MDA-MB-321 cell surface, which improved the delivery of therapeutic P12 peptide inside targeted cells. Au@p12 + CRGDK nanoparticles indicated with highly effective cancer treatment by increasing p53 expression upregulated with intracellular enhanced p12 therapeutic peptide. These results have implications to design and functionalize different molecules onto AuNPs surfaces to make hybrid model system for selective target binding as well as therapeutic effects for cancer treatment. PMID- 22056755 TI - Influence of perfusion and compression on the proliferation and differentiation of bone mesenchymal stromal cells seeded on polyurethane scaffolds. AB - In the present study, a porous meniscal-shaped scaffold consisting of polyurethane (PU)-based 1, 4-butanediisocyanate (BDI), which provided a 3-D culture condition for human bone mesenchymal stromal cells (hBMSC) was employed. A bioreactor was utilized to produce perfusion and mechanical stimulations. The viability, proliferation and fibro-cartilaginous differentiation of the hBMSC cultured on the PU-based meniscal scaffold were investigated during the perfusion and mechanical stimulation process. In addition, the mechanical properties of the cell-laden scaffolds were examined as well. Our finding indicated that the perfusion (10 ml/min) and on-off cyclic compressions mechanical stimulation (10% strain, 0.5 Hz, 4 times/day, 2 h/time with 4 h of rest thereafter) maintained the viability and promoted the proliferation of hBMSC over 2 weeks. The on-off cyclic compression caused a 1.85 fold increase in equilibrium modulus. Meanwhile, type I procollagen produced by hBMSC was increased for 3.02-fold after 2 weeks culture. On the other hand, the irrigating medium enhanced the synthesis of type III procollagen for 2.24-fold after 2 weeks. Tensile modulus was elevated for 2.02 fold in perfusion group after 1 week, which was decreased after 2 weeks unexpectedly. Our study suggests that the perfusion and on-off compression are promising to enhance the functional properties of the hBMSC-laden PU-based meniscal scaffold. PMID- 22056756 TI - Fluctuations of tensile strength and hardness of c-BC2N crystals induced by difference in atomic configuration. AB - At the atomistic level, the physical properties of a material are determined by its structure such as atomic arrangements. Here first-principles calculations were performed to investigate the effect of atomic configuration on the tensile strength and Vickers hardness of cubic-BC2N (c-BC2N) crystals. Depending on the degree of mixture between diamond and c-BN, the tensile strength of c-BC2N crystals can vary drastically from 27 to 77 GPa. The magnitude of the Vickers hardness fluctuations (~10 GPa) is also comparable to the experimental difference (~14 GPa). Thus, atomic-scale characterization of c-BC2N crystal structures may unveil the discrepancy of the measured Vickers hardness in experiments, and uncover the obvious differences of tensile strength described in theoretical calculations. PMID- 22056757 TI - Long-term follow-up of myopic choroidal neovascularization treated with ranibizumab. AB - PURPOSE: To evaluate the long-term safety and efficacy of intravitreal ranibizumab in the treatment of myopic choroidal neovascularization (CNV). METHODS: Three-year retrospective, nonrandomized, interventional case series. Forty eyes of 39 patients with myopic CNV were included; 15 with previous photodynamic therapy, and 25 naive eyes. Best-corrected visual acuity (BCVA) changes, central foveal thickness (CFT), and number of treatments were assessed, from baseline to month 36. RESULTS: Mean visual acuity improved from 55.4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 59.7 letters at 12 months (p = 0.07), 61.8 letters at 24 months (p = 0.008) and 63.4 letters at 36 months (p = 0.039). Twenty-five percent of the patients gained >=15 letters (3 lines) at 12 months, 30% at 24 months and 35% at 36 months. There was a mean reduction of 80 MUm in CFT (p < 0.001). A mean of 4.1 injections were performed in the first year, 2.4 in the second year and 1.1 in the third year. Fifty-three percent of the eyes had no need for treatment during the third year of follow-up. CONCLUSIONS: Intravitreal ranibizumab seems to be an effective and safe therapeutic procedure to treat CNV in highly myopic eyes, with a high proportion of patients gaining or stabilizing BCVA at a 3-year follow-up. PMID- 22056758 TI - Comments about the article by Mouterde et al. entitled "Indications of glucocorticoids in early arthritis and rheumatoid arthritis: Recommendations for clinical practice based on data from the literature and expert opinions". Joint Bone Spine 2010;77:597-603. Low-dose prednisone and biologics: allies rather than competitors? PMID- 22056759 TI - Vitamin D insufficiency: evaluation of an oral standardized supplementation using 100,000 IU vials of cholecalciferol, depending on initial serum level of 25OH vitamin D. AB - OBJECTIVES: There is no protocol of vitamin D supplementation used worldwide due to a great disparity of vitamin D supplements available in different countries. The aim of this study was to evaluate the efficiency of the protocol most often used in France to correct vitamin D deficiency defined by a serum 25-hydroxy vitamin D (25OHD) level of less than 30 ng/mL. METHODS: This was a pragmatic multicentric study of vitamin D supplementation in 257 osteopenic/osteoporotic, vitamin D deficient patients who received 100,000 UI vitamin D3 vials every two weeks according to their initial serum 25OHD level (four vials when 25OHD less than 10 ng/mL, three when 25OHD was 10-19 ng/mL, two when 25OHD was 20-29 ng/mL). Blood samples were obtained at baseline, one (M1), two (M2), and three months (M3), after the end of the supplementation protocol. RESULTS: At M1, 198/257 (77%) patients had a serum 25OHD level more than 30 ng/mL. Eighty-five percent of those with a BMI less than 25 kg/m2 had a 25OHD concentration more than 30 ng/mL, whereas only 66% of those with a BMI more than 25 had a level more than 30 ng/mL. At M2 and M3, 25OHD levels decreased significantly with 55% and 46% having still a level more than 30 ng/mL respectively, without any significant difference according to the initial 25OHD level. CONCLUSION: This protocol was effective in rising serum 25OHD of most vitamin D insufficient patients with a BMI less than 25 kg/m2, but not in overweight patients. As almost one half of our patients had a serum 25OHD level less than 30 ng/mL at M2, we suggest that regular doses should be started quite soon after this initial supplementation. PMID- 22056760 TI - Tanycytic ependymoma of filum terminale: a case report. AB - Tanycytic ependymoma is an uncommon but well-recognized variant of ependymoma. Here we report a case of tanycytic ependymoma occurring at the region of filum terminale in a 44-year male who presented with low backache, bilateral lower limb weakness and urinary incontinence. MR imaging in this patient showed a lesion that was composed of solid and cystic components and was suggestive of ependymoma. The filum terminale region is an extremely unusual location for the occurrence of tanycytic ependymoma. To the best of our knowledge this is the third case of tanycytic ependymoma occurring in the filum terminale region. PMID- 22056761 TI - Management of symptomatic intrathecal catheter-associated inflammatory masses. AB - OBJECTIVE: Intrathecal catheter-associated inflammatory masses (CIMs) are a serious complication of implanted drug pumps. The goal of this study was to review our experience with CIMs, including the pathology of all resected CIMs, and identify objective data which may guide management. METHODS: We performed a retrospective review of 13 patients who developed symptomatic CIMs during continuous intrathecal opioid therapy for chronic pain. Eight patients presented with pain plus neurologic deficit and 5 patients presented with pain alone. RESULTS: CIM resection via laminectomy and intradural exploration was ultimately performed in 8 patients, 3 of whom were initially treated with a non-resective surgical approach (catheter repositioning or pump removal) that failed. All 3 patients who experienced a failure with non-resective surgery had CIMs located in the thoracic spine with a maximum diameter>=13 mm and 2 of these patients had neurologic deficits on presentation. CONCLUSIONS: Our experience, with the largest reported single-surgeon series of patients harboring CIMs, favors early resection, especially in patients with neurologic deficit. Resection may also be a prudent first-line strategy for patients with larger thoracic masses (>=13 mm) regardless of neurologic status. Neurologic deficits engendered by CIM usually improve after resection and the majority of patients in our series would have still elected to have an intrathecal pump for pain control knowing a CIM would have developed. PMID- 22056762 TI - An analysis of related factors of surgical results for patients with craniopharyngiomas. AB - OBJECTIVE: The objective of this study was to retrospectively review the surgical results following gross total resection and partial resection with or without radiotherapy for craniopharyngiomas and analyze the related factors of surgical results. METHODS: From 1994 to 2009, 214 patients underwent 219 procedures for craniopharyngiomas. We retrospectively reviewed the pre- and postoperative data of patients, reported the perioperative and long-term surgical results and analyzed the influencing factors and the relationship between hypothalamic involvement and postoperative quality of life. RESULTS: Gross total resection was achieved in 154 procedures (70.3%). Perioperative mortality was 5%. Perioperative hyperpyrexia was the most significant risk factor for perioperative mortality. A total of 151 patients were followed from 6 months to 190 months. There were significant differences in recurrence rate and overall survival between gross total resection and limited resection (P<0.05). There was significant difference in recurrence rate between limited resection and limited resection with radiotherapy (P<0.01), but it did not reach statistical difference between gross total resection and gross total resection with radiotherapy. The factors strongly influencing overall survival include old patients, partial resection and recurrent tumors. The preoperative hypothalamic involvement negatively correlates with the postoperative quality of life in patients with craniopharyngiomas. CONCLUSION: The preoperative CT/MR imaging provides clues of the relationship between tumor and surrounding structures. Gross total resection should be achieved in the treatment of craniopharyngiomas on the condition that hypothalamus is preserved. The patients who undergo limited resection should receive conventional radiotherapy or gamma knife surgery. PMID- 22056763 TI - Roles of PPARs in NAFLD: potential therapeutic targets. AB - Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increasing prevalence due to the obesity epidemic. Hence, NAFLD represents a rising threat to public health. Currently, no effective treatments are available to treat NAFLD and its complications such as cirrhosis and liver cancer. Peroxisome proliferator activated receptors (PPARs) are ligand-activated nuclear receptors which regulate lipid and glucose metabolism as well as inflammation. Here we review recent findings on the pathophysiological role of PPARs in the different stages of NAFLD, from steatosis development to steatohepatitis and fibrosis, as well as the preclinical and clinical evidence for potential therapeutical use of PPAR agonists in the treatment of NAFLD. PPARs play a role in modulating hepatic triglyceride accumulation, a hallmark of the development of NAFLD. Moreover, PPARs may also influence the evolution of reversible steatosis toward irreversible, more advanced lesions. Presently, large controlled trials of long duration are needed to assess the long-term clinical benefits of PPAR agonists in humans. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID- 22056764 TI - The apoptotic effects of the flavonoid N101-2 in human cervical cancer cells. AB - This study evaluated the anti-cancer effects of a naringenin derivative in human cervical cancer cells. In this study, a synthesized naringenin derivative, diethyl 5,7,4'-trihydroxy flavanone N-phenyl hydrazone (N101-2), inhibited cervical cancer cell growth, whereas naringenin itself exhibited no anti-cancer activity. N101-2 treatment inhibited cancer cell viability in a dose- and time dependent manner through cell cycle arrest at sub-G1 phase, accompanied by an increase in apoptotic cell death. Expression of cyclins and ppRB was down regulated, whereas that of CDK inhibitors and p53 increased upon N101-2 treatment. Meanwhile, we detected processing of caspases-8, -9, and -3, cleavage of PARP, as well as Bax up-regulation, which indicates activation of mitochondria emanated intrinsic apoptosis signaling. Treatment with caspase-8 and -3 inhibitors also recovered cell cycling, and Fas/FasL expression increased in N101 2-treated cervical cancer cells, suggesting that Fas-mediated extrinsic apoptosis signaling was also activated. The tumor suppressor PTEN and its upstream regulator PPARgamma were up-regulated with coincident inhibition of PI3K and phospho-Akt after N101-2 treatment. Taken together, we could conclude that N101-2 induces apoptosis by arresting the cell cycle at sub-G1 phase, activating mitochondria-emanated intrinsic and Fas-mediated extrinsic signaling pathways, and inhibiting the PI3K/AKT pathway in CaSki and SiHa human cervical cancer cells. PMID- 22056765 TI - Enhancement of nitrite on heme-induced oxidative reactions: A potential toxicological implication. AB - Evidence to support the role of heme as major inducers of oxidative damage is increasingly present. Nitrite (NO(2)(-)) is one of the major end products of NO metabolism. Although the biological significance of heme/NO(2)(-)-mediated protein tyrosine nitration is a subject of great interest, the important roles of NO(2)(-) on heme-dependent redox reaction have been greatly underestimated. In this study, we investigated the influence of NO(2)(-) on heme -dependent oxidative reactions. It was found that NO(2)(-) had the capacity to act as a reducing agent to remove high oxidation states of heme iron. In the reduction of ferryl heme to ferric heme, NO(2)(-) was oxidized to a nitrating agent NO(2), and subsequently, tyrosine residues in bovine serum albumin (BSA) were nitrated. However, the presence of NO(2)(-) surprisingly exerted pro-oxidant effect on heme H(2)O(2)-induced formation of BSA carbonyls at lower concentrations and enhanced the loss of HepG2 cell viability dose-dependently, which was probably due to the ability of this inorganic compound to efficiently enhance the peroxidase activity and oxidative degradation of heme. These data provide novel evidence that the dietary intake and experimental use of NO(2)(-) in vivo and in vitro would possess the pro-oxidant activity through interfering in heme-dependent oxidative reactions. Besides the classic role in protein tyrosine nitration, the deleterious effects on heme redox reactions may provide new insights into the toxicological implications of NO(2)(-) with cellular heme proteins. PMID- 22056766 TI - Heme oxygenase-1 mediates the protective role of quercetin against ethanol induced rat hepatocytes oxidative damage. AB - Quercetin, one of the most widely distributed flavonoids in plants, possesses strong free radical scavenging ability and potent hepatoprotective effects. However, the protective effect and mechanism of quercetin on ethanol-induced oxidative damage in hepatocytes remain unclear. In this study, primary rat hepatocytes were incubated with ethanol and quercetin in the presence or absence of ZnPP 9, an antagonist of HO-1 induction. The ethanol-induced hepatotoxicity was found to be greatly diminished by pre-treatment of quercetin and this hepatoprotective effect could be partly blocked by ZnPP 9. This study also showed that quercetin significantly stimulated HO-1 expression at both mRNA and protein levels, then subsequently induced HO-1 activity. To further study the signaling pathways underlying quercetin-induced HO-1 up-regulation, HO-1 expression and activity in cytosolic microsomal fractions and Nrf2 expression in nuclear fractions were analyzed following quercetin or/and MAPK inhibitor(s) as well as PI3K inhibitor incubation for primary rat hepatocytes. These results indicated that ERK was required to induce HO-1 expression in rat hepatocytes. In summary, these data suggested that quercetin attenuates ethanol-induced oxidative stress through a pathway which involves ERK activation and HO-1 upregulation. PMID- 22056767 TI - Effects of population density and chemical environment on the behavior of Escherichia coli in shallow temperature gradients. AB - In shallow temperature gradients, changes in temperature that bacteria experience occur over long time scales. Therefore, slow processes such as adaptation, metabolism, chemical secretion and even gene expression become important. Since these are cellular processes, the cell density is an important parameter that affects the bacteria's response. We find that there are four density regimes with distinct behaviors. At low cell density, bacteria do not cause changes in their chemical environment; however, their response to the temperature gradient is strongly influenced by it. In the intermediate cell-density regime, the consumption of nutrients becomes significant and induces a gradient of nutrients opposing the temperature gradient due to higher consumption rate at the high temperature. This causes the bacteria to drift toward low temperature. In the high cell-density regime, interactions among bacteria due to secretion of an attractant lead to a strong local accumulation of bacteria. This together with the gradient of nutrients, resulted from the differential consumption rate, creates a fast propagating pulse of bacterial density. These observations are a result of classical nonlinear population dynamics. At extremely high cell density, a change in the physiological state of the bacteria is observed. The bacteria, at the individual level, become cold seeking. This appears initially as a result of a change in the methylation level of the two most abundant sensing receptors, Tsr and Tar. It is further enforced at an even higher cell density by a change in the expression level of these receptors. PMID- 22056768 TI - Epidemiology of snakebites in Europe: a systematic review of the literature. AB - Snakebites are rare medical emergency cases in Europe but may sometimes be severe and lead to complications. A better knowledge of snakebite epidemiology may help health authorities to better understand therapeutic requirements, especially concerning antivenoms, and thus improve treatment of snakebite. An extensive literature search for studies and articles published between 1970 and 2010 was performed. Both indexed and non-indexed articles were examined, the analysis of which took into account the heterogeneity between the studies and weighted the studies according to size of the study population covered. Most of the articles involved hospitalized patients who represented more than 90% of snakebites. Incidence, mortality and population at risk were estimated after stratification into three regions (northern, central and southern Europe) based both on viper species distribution and climatic characteristics. There was no significant variation in incidence from the north to the south of Europe. In the whole of Europe, including European Russia and Turkey, the annual number of snakebite cases was estimated at 7992 [CI 95% = 6860-9178] bites, out of which approximately 15% were considered severe (grade 3). These bites usually occurred between May and September, with a more dispersed distribution in southern Europe. The average number of deaths per annum was 4 [0.7-7.7]. Children and male victims are more affected, contrary to what one would expect given their respective proportion in the entire population. Both upper and lower limb bites were recorded at an equal frequency while the bites in other parts of the body were very rare. Immunotherapy was prescribed in one out of three snakebites in Europe, with a very high geographical variability, in spite of excellent tolerance, at least considering highly-purified immunoglobulin fragments. Snakebites are uncommon in Europe but can cause life-threatening envenomation. Fragments of highly-purified immunoglobulins are now very well tolerated and dramatically reduce both severity and mortality of snakebites when used in treatment. PMID- 22056769 TI - Structure of green-type Rubisco activase from tobacco. AB - Rubisco, the enzyme that catalyzes the fixation of atmospheric CO(2) in photosynthesis, is subject to inactivation by inhibitory sugar phosphates. Here we report the 2.95-A crystal structure of Nicotiana tabacum Rubisco activase (Rca), the enzyme that facilitates the removal of these inhibitors. Rca from tobacco has a classical AAA(+)-protein domain architecture. Although Rca populates a range of oligomeric states when in solution, it forms a helical arrangement with six subunits per turn when in the crystal. However, negative stain electron microscopy of the active mutant R294V suggests that Rca functions as a hexamer. The residues determining species specificity for Rubisco are located in a helical insertion of the C-terminal domain and probably function in conjunction with the N-domain in Rubisco recognition. Loop segments exposed toward the central pore of the hexamer are required for the ATP-dependent remodeling of Rubisco, resulting in the release of inhibitory sugar. PMID- 22056770 TI - Structural basis for the molecular evolution of SRP-GTPase activation by protein. AB - Small G proteins have key roles in signal transduction pathways. They are switched from the signaling 'on' to the non-signaling 'off' state when GTPase activating proteins (GAPs) provide a catalytic residue. The ancient signal recognition particle (SRP)-type GTPases form GTP-dependent homo- and heterodimers and deviate from the canonical switch paradigm in that no GAPs have been identified. Here we show that the YlxH protein activates the SRP-GTPase FlhF. The crystal structure of the Bacillus subtilis FlhF-effector complex revealed that the effector does not contribute a catalytic residue but positions the catalytic machinery already present in SRP-GTPases. We provide a general concept that might also apply to the RNA-driven activation of the universally conserved, co translational protein-targeting machinery comprising the SRP-GTPases Ffh and FtsY. Our study exemplifies the evolutionary transition from RNA- to protein driven activation in SRP-GTPases and suggests that the current view on SRP mediated protein targeting is incomplete. PMID- 22056771 TI - Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8. AB - Autophagy is the degradation of cellular organelles via the lysosomal pathway. The autophagic ubiquitin-like (Ubl) molecule Atg8 is activated by the E1-like enzyme Atg7. As this noncanonical E1 enzyme's domain organization is unique among Ubl-activating E1 enzymes, the structural basis for its interactions with Atg8 and partner E2 enzymes remains obscure. Here we present the structure of the N terminal domain of Atg7, revealing a unique protein fold and interactions with both autophagic E2 enzymes Atg3 and Atg10. The structure of the C-terminal domain of Atg7 in complex with Atg8 shows the mode of dimerization and mechanism of recognition of Atg8. Notably, the catalytic cysteine residue in Atg7 is positioned close to the C-terminal glycine of Atg8, its target for thioester formation, potentially eliminating the need for large conformational rearrangements characteristic of other E1s. PMID- 22056772 TI - Molecular profiling of common fragile sites in human fibroblasts. AB - Common fragile sites have been mapped primarily in lymphocytes, but recent analyses show that the setting of these sites relies on cell type-dependent replication programs. Using a new approach, we molecularly mapped common fragile sites in human fibroblasts and showed that commitment to fragility depends on similar replication features in fibroblasts and lymphocytes, although different loci are committed in each cell type. Notably, the common fragile sites that we identified overlapped heretofore unexplained deletion clusters observed in tumors. PMID- 22056773 TI - Total RNA sequencing reveals nascent transcription and widespread co transcriptional splicing in the human brain. AB - Transcriptome sequencing allows for analysis of mature RNAs at base pair resolution. Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription. We sequenced total RNA from human brain and liver and found a large fraction of reads (up to 40%) within introns. Intronic RNAs were abundant in brain tissue, particularly for genes involved in axonal growth and synaptic transmission. Moreover, we detected significant differences in intronic RNA levels between fetal and adult brains. We show that the pattern of intronic sequence read coverage is explained by nascent transcription in combination with co-transcriptional splicing. Further analysis of co-transcriptional splicing indicates a correlation between slowly removed introns and alternative splicing. Our data show that sequencing of total RNA provides unique insight into the transcriptional processes in the cell, with particular importance for normal brain development. PMID- 22056774 TI - Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein. AB - Herpesvirus-associated ubiquitin-specific protease (HAUSP) regulates the stability of p53 and the p53-binding protein MDM2, implicating HAUSP as a therapeutic target for tuning p53-mediated antitumor activity. Here we report the structural analysis of HAUSP with Kaposi's sarcoma-associated herpesvirus viral interferon (IFN) regulatory factor 4 (vIRF4) and the discovery of two vIRF4 derived peptides, vif1 and vif2, as potent and selective HAUSP antagonists. This analysis reveals a bilateral belt-type interaction that results in inhibition of HAUSP. The vif1 peptide binds the HAUSP TRAF domain, competitively blocking substrate binding, whereas the vif2 peptide binds both the HAUSP TRAF and catalytic domains, robustly suppressing its deubiquitination activity. Peptide treatments comprehensively blocked HAUSP, leading to p53-dependent cell-cycle arrest and apoptosis in culture and to tumor regression in xenograft mouse model. Thus, the virus has developed a unique strategy to target the HAUSP-MDM2-p53 pathway, and these virus-derived short peptides represent biologically active HAUSP antagonists. PMID- 22056775 TI - Imported malaria in Scotland--an overview of surveillance, reporting and trends. AB - BACKGROUND: Imported malaria cases continue to occur and are often underreported. This study assessed reporting of malaria cases and their characteristics in Scotland. METHODS: Cases were identified at the study sites of Aberdeen, Edinburgh, Glasgow and Inverness. The number of cases identified in the period 2003-2008 was compared to surveillance databases from Health Protection Scotland (HPS) and the Malaria Reference Laboratory (MRL). Case characteristics were recorded and analysed. RESULTS: Of 252 cases of malaria diagnosed and treated, an estimated 235 (93.3%) were reported to the MRL. Between 2006 and 2008, 114 of 126 cases (90.5%) were reported to HPS. Plasmodium falciparum caused 173 cases (68.7%). Business and professional travel accounted for 35.3% of cases (higher in Aberdeen), followed by visiting friends and relatives (33.1%) and holiday makers (25.5%). The majority of infections were imported from West Africa and 65.7% of patients for whom data on prophylaxis was available had taken no or inappropriate prophylaxis. CONCLUSIONS: Reporting of malaria in Scotland can be improved. There is a continued need to optimise preventive measures and adherence to chemoprophylaxis amongst business travellers, those visiting friends and relatives, and holiday makers in endemic countries in order to reduce imported malaria cases. PMID- 22056776 TI - An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment. AB - The role of DNA sequence in determining chromatin state is incompletely understood. We have previously demonstrated that large chromosomal segments from human cells recapitulate their native chromatin state in mouse cells, but the relative contribution of local sequences versus their genomic context remains unknown. In this study, we compare orthologous chromosomal regions for which the human locus establishes prominent sites of Polycomb complex recruitment in pluripotent stem cells, whereas the corresponding mouse locus does not. Using recombination-mediated cassette exchange at the mouse locus, we establish the primacy of local sequences in the encoding of chromatin state. We show that the signal for chromatin bivalency is redundantly encoded across a bivalent domain and that this reflects competition between Polycomb complex recruitment and transcriptional activation. Furthermore, our results suggest that a high density of unmethylated CpG dinucleotides is sufficient for vertebrate Polycomb recruitment. This model is supported by analysis of DNA methyltransferase deficient embryonic stem cells. PMID- 22056777 TI - Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest. AB - The spindle assembly checkpoint (SAC), an evolutionarily conserved surveillance pathway, prevents chromosome segregation in response to conditions that disrupt the kinetochore-microtubule attachment. Removal of the checkpoint-activating stimulus initiates recovery during which spindle integrity is restored, kinetochores become bi-oriented, and cells initiate anaphase. Whether recovery ensues passively after the removal of checkpoint stimulus, or requires mediation by specific effectors remains uncertain. Here, we report two unrecognized functions of yeast Cdk1 required for efficient recovery from SAC-induced arrest. We show that Cdk1 promotes kinetochore bi-orientation during recovery by restraining premature spindle elongation thereby extinguishing SAC signalling. Moreover, Cdk1 is essential for sustaining the expression of Cdc20, an activator of the anaphase promoting complex/cyclosome (APC/C) required for anaphase progression. We suggest a model in which Cdk1 activity promotes recovery from SAC induced mitotic arrest by regulating bi-orientation and APC/C activity. Our findings provide fresh insights into the regulation of mitosis and have implications for the therapeutic efficacy of anti-mitotic drugs. PMID- 22056778 TI - Structural basis of initial RNA polymerase II transcription. AB - During transcription initiation by RNA polymerase (Pol) II, a transient open promoter complex (OC) is converted to an initially transcribing complex (ITC) containing short RNAs, and to a stable elongation complex (EC). We report structures of a Pol II-DNA complex mimicking part of the OC, and of complexes representing minimal ITCs with 2, 4, 5, 6, and 7 nucleotide (nt) RNAs, with and without a non-hydrolyzable nucleoside triphosphate (NTP) in the insertion site +1. The partial OC structure reveals that Pol II positions the melted template strand opposite the active site. The ITC-mimicking structures show that two invariant lysine residues anchor the 3'-proximal phosphate of short RNAs. Short DNA-RNA hybrids adopt a tilted conformation that excludes the +1 template nt from the active site. NTP binding induces complete DNA translocation and the standard hybrid conformation. Conserved NTP contacts indicate a universal mechanism of NTP selection. The essential residue Q1078 in the closed trigger loop binds the NTP 2'-OH group, explaining how the trigger loop couples catalysis to NTP selection, suppressing dNTP binding and DNA synthesis. PMID- 22056779 TI - [Erectile dysfunction in polycythemia vera]. PMID- 22056780 TI - [New treatments of chronic hepatitis C]. AB - The current treatment of chronic hepatitis C since several years, the association of pegylated interferon and ribavirine, allows to obtain a virological eradication in 55% of patients, all genotypes and 45% of those infected with the genotype 1, the most prevalent. The cure, defined by an undetectable viremia 24 weeks after the discontinuation of treatment is associated to a improvement of the prognosis of the patients with a decrease of mortality and morbidity. The development of news antiviral C molecules, efficient against the genotype 1, two protease inhibitors, boceprevir or telaprevir (which approval has been recently obtained), in association with pegylated interferon and ribavirine, allows to obtain a viral eradication in 70 to 75% of cases, with a reduction of treatment duration to 24 weeks in half of patients. This evolution will modify the therapeutic indications, the therapeutic schemas, the virologic follow-up, the risk factors of sustained virological reponse, the tolerance with the appearance of new adverse effects. PMID- 22056781 TI - Gender differences in the types and frequency of coronary artery anomalies. AB - Coronary artery anomalies are rarely encountered in general population. Gender may play a role in the types and incidence of coronary artery anomalies, although the effect of gender is not well established. In the present study, we therefore aimed to investigate the frequency and location of various types of coronary artery anomalies and their correlation with gender. We assessed retrospectively the coronary angiography movies of 7,810 patients (2,214 females and 5,596 males), the method of which is distinct from the earlier studies with angiographic archive records. We defined and classified the coronary artery anomalies according to their origin, course (myocardial bridge), and termination (fistula). The incidence of coronary artery anomalies was 3.35% (262 of 7,810): 130 individuals with anomalous origin (1.66%), 105 individuals with myocardial bridges (1.34%), and 27 with fistulas (0.35%). The frequency of the coronary artery anomalies was significantly higher in the females than the males (p = 0.001). Of the coronary artery origin anomalies, the circumflex and the left anterior descending artery originating from separate ostia in the left aortic sinus were higher in the females compared to the males (P < 0.001). In contrast, the frequency of myocardial bridges was higher in the males (P = 0.01). No gender difference was detected in fistulas. Thus, gender affects the types of coronary artery anomalies, except for fistulas. The determination of the presence of the coronary artery anomalies during the coronary angiography is critical for the planning of the treatment and for the proper clinical follow-up of patients. PMID- 22056782 TI - Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/beta-catenin signaling pathway. AB - Zic3 controls neuroectodermal differentiation and left-right patterning in Xenopus laevis embryos. Here we demonstrate that Zic3 can suppress Wnt/beta catenin signaling and control development of the notochord and Spemann's organizer. When we overexpressed Zic3 by injecting its RNA into the dorsal marginal zone of 2-cell-stage embryos, the embryos lost mesodermal dorsal midline structures and showed reduced expression of organizer markers (Siamois and Goosecoid) and a notochord marker (Xnot). Co-injection of Siamois RNA partially rescued the reduction of Xnot expression caused by Zic3 overexpression. Because the expression of Siamois in the organizer region is controlled by Wnt/beta catenin signaling, we subsequently examined the functional interaction between Zic3 and Wnt signaling. Co-injection of Xenopus Zic RNAs and beta-catenin RNA with a reporter responsive to the Wnt/beta-catenin cascade indicated that Zic1, Zic2, Zic3, Zic4, and Zic5 can all suppress beta-catenin-mediated transcriptional activation. In addition, co-injection of Zic3 RNA inhibited the secondary axis formation caused by ventral-side injection of beta-catenin RNA in Xenopus embryos. Zic3-mediated Wnt/beta-catenin signal suppression required the nuclear localization of Zic3, and involved the reduction of beta-catenin nuclear transport and enhancement of beta-catenin degradation. Furthermore, Zic3 co precipitated with Tcf1 (a beta-catenin co-factor) and XIC (I-mfa domain containing factor required for dorsoanterior development). The findings in this report produce a novel system for fine-tuning of Wnt/beta-catenin signaling. PMID- 22056783 TI - Leucine and arginine regulate trophoblast motility through mTOR-dependent and independent pathways in the preimplantation mouse embryo. AB - Uterine implantation is a critical element of mammalian reproduction and is a tightly and highly coordinated event. An intricate and reciprocal uterine-embryo dialog exists to synchronize uterine receptivity with the concomitant activation of the blastocyst, maximizing implantation success. While a number of pathways involved in regulating uterine receptivity have been identified in the mouse, less is understood about blastocyst activation, the process by which the trophectoderm (TE) receives extrinsic cues that initiate new characteristics essential for implantation. Amino acids (AA) have been found to regulate blastocyst activation and TE motility in vitro. In particular, we find that arginine and leucine alone are necessary and sufficient to induce TE motility. Both arginine and leucine act individually and additively to propagate signals that are dependent on the activity of the mammalian target of rapamycin complex 1 (mTORC1). The activities of the well-established downstream targets of mTORC1, p70S6K and 4EBP, do not correlate with trophoblast motility, suggesting that an independent-rapamycin-sensitive pathway operates to induce trophoblast motility, or that other, parallel amino acid-dependent pathways are also involved. We find that endogenous uterine factors act to induce mTORC1 activation and trophoblast motility at a specific time during pregnancy, and that this uterine signal is later than the previously defined signal that induces the attachment reaction. In vivo matured blastocysts exhibit competence to respond to an 8-hour AA stimulus by activating mTOR and subsequently undergoing trophoblast outgrowth by the morning of day 4.5 of pregnancy, but not on day 3.5. By the late afternoon of day 4.5, the embryos no longer require any exposure to AA to undergo trophoblast outgrowth in vitro, demonstrating the existence and timing of an equivalent in vivo signal. These results suggest that there are two separate uterine signals regulating implantation, one that primes the embryo for the attachment reaction and another that activates mTOR and initiates invasive behavior. PMID- 22056784 TI - SOHLH1 and SOHLH2 coordinate spermatogonial differentiation. AB - Spermatogonial self-renewal and differentiation are essential for male fertility and reproduction. We discovered that germ cell specific genes Sohlh1 and Sohlh2, encode basic helix-loop-helix (bHLH) transcriptional regulators that are essential in spermatogonial differentiation. Sohlh1 and Sohlh2 individual mouse knockouts show remarkably similar phenotypes. Here we show that SOHLH1 and SOHLH2 proteins are co-expressed in the entire spermatogonial population except in the GFRA1(+) spermatogonia, which includes spermatogonial stem cells (SSCs). SOHLH1 and SOHLH2 are expressed in both KIT negative and KIT positive spermatogonia, and overlap Ngn3/EGFP and SOX3 expression. SOHLH1 and SOHLH2 heterodimerize with each other in vivo, as well as homodimerize. The Sohlh1/Sohlh2 double mutant phenocopies single mutants, i.e., spermatogonia continue to proliferate but do not differentiate properly. Further analysis revealed that GFRA1(+) population was increased, while meiosis commenced prematurely in both single and double knockouts. Sohlh1 and Sohlh2 double deficiency has a synergistic effect on gene expression patterns as compared to the single knockouts. SOHLH proteins affect spermatogonial development by directly regulating Gfra1, Sox3 and Kit gene expression. SOHLH1 and SOHLH2 suppress genes involved in SSC maintenance, and induce genes important for spermatogonial differentiation. PMID- 22056785 TI - Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development. AB - During mouse pancreas development, the transient expression of Neurogenin3 (Neurog3) in uncommitted pancreas progenitors is required to determine endocrine destiny. However it has been reported that Neurog3-expressing cells can eventually adopt acinar or ductal fates and that Neurog3 levels were important to secure the islet destiny. It is not known whether the competence of Neurog3 induced cells to give rise to non-endocrine lineages is an intrinsic property of these progenitors or depends on pancreas developmental stage. Using temporal genetic labeling approaches we examined the dynamic of endocrine progenitor differentiation and explored the plasticity of Neurog3-induced cells throughout development. We found that Neurog3(+) progenitors develop into hormone-expressing cells in a fast process taking less then 10h. Furthermore, fate-mapping studies in heterozygote (Neurog3(CreERT/+)) and Neurog3-deficient (Neurog3(CreERT/CreERT)) embryos revealed that Neurog3-induced cells have different potential over time. At the early bud stage, failed endocrine progenitors can adopt acinar or ductal fate, whereas later in the branching pancreas they do not contribute to the acinar lineage but Neurog3-deficient cells eventually differentiate into duct cells. Thus these results provide evidence that the plasticity of Neurog3-induced cells becomes restricted during development. Furthermore these data suggest that during the secondary transition, endocrine progenitor cells arise from bipotent precursors already committed to the duct/endocrine lineages and not from domain of cells having distinct potentialities. PMID- 22056786 TI - ETS-dependent regulation of a distal Gata4 cardiac enhancer. AB - The developing heart contains an inner tube of specialized endothelium known as endocardium, which performs multiple essential functions. In spite of the essential role of the endocardium in heart development and function, the transcriptional pathways that regulate its development remain largely undefined. GATA4 is a zinc finger transcription factor that is expressed in multiple cardiovascular lineages and is required for endocardial cushion development and embryonic viability, but the transcriptional pathways upstream of Gata4 in the endocardium and its derivatives in the endocardial cushions are unknown. Here, we describe a distal enhancer from the mouse Gata4 gene that is briefly active in multiple cardiac lineages early in cardiac development but restricts to the endocardium where it remains active through cardiogenesis. The activity of this Gata4 cardiac enhancer in transgenic embryos and in cultured aortic endothelial cells is dependent on four ETS sites. To identify which ETS transcription factors might be involved in Gata4 regulation via the ETS sites in the enhancer, we determined the expression profile of 24 distinct ETS factors in embryonic mouse hearts. Among multiple ETS transcripts present, ETS1, FLI1, ETV1, ETV5, ERG, and ETV6 were the most abundant in the early embryonic heart. We found that ETS1, FLI1, and ERG were strongly expressed in the heart at embryonic day 8.5 and that ETS1 and ERG bound to the endogenous Gata4 enhancer in cultured endothelial cells. Thus, these studies define the ETS expression profile in the early embryonic heart and identify an ETS-dependent enhancer from the Gata4 locus. PMID- 22056787 TI - Developing and measuring a set of process and outcome indicators for breast cancer. AB - PURPOSE: This study aimed at developing and measuring a set of indicators to monitor the quality of breast cancer care, to make comparisons over time and to support quality improvement for all practitioners and centres involved in the care of breast cancer women. METHODS: Quality indicators were identified from a systematic literature search and the 2010 Belgian evidence-based clinical practice guideline. The selection process involved an expert panel evaluating reliability, relevance, interpretability and actionability of each indicator. The quality indicators were tested using the Belgian Cancer Registry data linked with claims data for all women registered with breast cancer in Belgium between 2001 and 2006 (n=50,039). RESULTS: The selection process led to a final set of 32 indicators. Of these, 12 were measurable using the available data, while 1 indicator was measurable using proxy information. Five-year relative survival was 98%, 87%, 68% and 29% for pStage I, II, III and cStage IV respectively. Overall 5 year survival slightly improved for pStage II, III and cStage IV between 2001 and 2004. Of the surgically treated women, 60% underwent breast conserving surgery, 85% received adjuvant systemic treatment and 86% were irradiated postoperatively. In 80% of women treated for breast cancer, at least one mammography was performed within one year after the last treatment. CONCLUSION: The present study demonstrates the feasibility to develop a multidisciplinary set of quality indicators for breast cancer. Using national cancer registry data linked to claims data, 13 indicators were measurable, showing results that largely correspond to other studies in the field. PMID- 22056788 TI - Editorial. Surgery has become more and more conservative. PMID- 22056789 TI - Contribution of lateral gene transfer to the gene repertoire of a gut-adapted methanogen. AB - Methanobrevibacter smithii is the most abundant archaeon in the human colon. As most of its neighbors are bacterial species, it is expected that lateral gene acquisition from bacteria might have contributed to the evolution and adaptation of this archaeon. We performed a tree-based genome-wide survey of putative lateral gene transfer products in M. smithii, using a phylogenetic pipeline. Over 15% of the coding genes of M. smithii are inferred to be bacterial in origin, based on this analysis. Laterally acquired genes have had the largest contribution to surface functions, and encode glycosyl-transferases and adhesin like proteins. In addition, several important ABC transporters, especially metal transporters are of bacterial origin. Thus, bacterial genes contributed to the host-adaptation by allowing a larger variety of surface structures and increasing the efficiency of metal ion uptake in the competitive gut niche. PMID- 22056790 TI - Sitagliptin, a dipeptidyl peptidase-IV inhibitor, improves psoriasis. AB - A patient with a 17-year history of plaque psoriasis accompanied by type 2 diabetes mellitus discontinued cyclosporine and steroid ointment given for treatment of psoriasis because she was dissatisfied with the effects of the drugs. After sitagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor, was administered for control of blood glucose, psoriatic skin lesions were gradually diminished, although HbA1c did not improve. Three months after the administration of sitagliptin, infiltration, scales and erythema on all psoriatic plaques disappeared, leaving pigmentation on flat skin. DPP-IV in serum degrades the incretin hormones which stimulate beta-cell insulin secretion. DPP-IV inhibitors, as incretin enhancers, cause an increase in glucose-dependent insulin secretion, and are applied for the treatment of diabetes mellitus. DPP-IV is also expressed on T cells as CD26, a surface antigen which plays an important role in activating T cells. As helper T cells are involved in the pathogenesis of psoriasis, it is possible that DPP-IV inhibitors improve psoriatic skin lesions by inhibiting T cell activation, independently of glycemic control. DPP-IV inhibitors could be an alternative for the treatment of psoriasis. PMID- 22056791 TI - Screening and differential diagnosis of renal light chain-associated diseases. AB - BACKGROUND: Renal involvement in the light chain-associated diseases multiple myeloma (MM), amyloidosis (AL) and monoclonal immune position disease (MIDD) is common and differential diagnosis usually requires renal biopsy. The aim of this study was to investigate if noninvasive methods are viable to identify and differentiate between the various types of kidney diseases. PATIENTS AND METHODS: All patients with a light chain-associated disease admitted to our center from 1996 to 2008 were retrospectively evaluated. Renal biopsy data were correlated with proteinuria findings. RESULTS: Only the ratio of free kappa/lambda light chains showed a good sensitivity for myeloma cast nephropathy (MCN), AL and MIDD. The lambda light chain was characteristic for AL, the kappa light chain dominated in MIDD. Renal function at the time of diagnosis was worst in MIDD. MCN presented with a proteinuria of > 3.5 g/g creatinine. In contrast, a higher proteinuria was found in AL or MIDD. Whereas the kappa/lambda ratio in the urine was pathological for all three diseases, extremely high or low ratios indicated the presence of MCN. However, in AL or MIDD, the ratio was only moderately elevated. CONCLUSION: A noninvasive differentiation between MCN and other forms of renal light chain disease is possible. PMID- 22056792 TI - [Pulmonary aspergillosis and HIV infection: about two cases]. AB - The occurrence of invasive pulmonary aspergillosis is unusual during the course of AIDS. Patients at risk have a CD4 T-lymphocyte count under 50 cells/mm(3) combined with other risk factors in 50% of the cases. Positive diagnosis is based on chest CT scan imaging and isolation of Aspergillus in broncho-alveolar fluid. Detection of galactomannan antigen in serum and broncho-alveolar lavage fluid (BALF) is a reliable complementary tool in assessing the diagnosis. The first line therapy is Voriconazole. The prognosis, often severe, depends on prompt initiation of the appropriate antifungal treatment. We report two cases of invasive pulmonary aspergillosis in AIDS patients. PMID- 22056793 TI - Computational modelling for the embolization of brain arteriovenous malformations. AB - Treatment of arteriovenous malformations (AVMs) of the brain often requires the injection of a liquid embolic material to reduce blood flow through the malformation. The type of the liquid and the location of injection have to be carefully planned in a pre-operative manner. We introduce a new model of the interaction of liquid embolic materials with blood for the simulation of their propagation and solidification in the AVM. Solidification is mimicked by an increase of the material's viscosity. Propagation is modelled by using the concept of two-fluids modelling and that of scalar transport. The method is tested on digital phantoms and on one anatomically derived patient AVM case. Simulations showed that intuitive behaviour of the two-fluid system can be confirmed and that two types of glue propagation through the malformation can be reproduced. Distinction between the two types of propagation could be used to identify fistulous and plexiform compartments composing the AVM and to characterize the solidification of the embolic material in them. PMID- 22056794 TI - Retained energy-based coding for EEG signals. AB - The recent use of long-term records in electroencephalography is becoming more frequent due to its diagnostic potential and the growth of novel signal processing methods that deal with these types of recordings. In these cases, the considerable volume of data to be managed makes compression necessary to reduce the bit rate for transmission and storage applications. In this paper, a new compression algorithm specifically designed to encode electroencephalographic (EEG) signals is proposed. Cosine modulated filter banks are used to decompose the EEG signal into a set of subbands well adapted to the frequency bands characteristic of the EEG. Given that no regular pattern may be easily extracted from the signal in time domain, a thresholding-based method is applied for quantizing samples. The method of retained energy is designed for efficiently computing the threshold in the decomposition domain which, at the same time, allows the quality of the reconstructed EEG to be controlled. The experiments are conducted over a large set of signals taken from two public databases available at Physionet and the results show that the compression scheme yields better compression than other reported methods. PMID- 22056795 TI - Novel broad-host-range vehicles for cloning and shuffling of gene cassettes. AB - Novel vectors for cloning and shuffling of gene cassettes based on minireplicon of broad-host-range RA3 plasmid from IncU incompatibility group were constructed. A series of minireplicon variants were prepared with copy number ranging from low (1-2 copies per chromosome), medium (10-15 copies per chromosome) to high copy number (80-90 copies per chromosome). The new cloning vectors are relatively small in size (4.5-5.4kb) and carry various resistance determinants: kanamycin (Km(R)), tetracycline (Tc(R)) or chloramphenicol (Cm(R)). The vectors were engineered to facilitate cloning and shuffling of the functional modules with or without transcriptional terminators. Using the described strategy, a bank of functional modules, ready for exchange, has been initiated. PMID- 22056796 TI - State of the art: urologic surgery. PMID- 22056797 TI - Laparoscopic cholecystectomy. PMID- 22056798 TI - DIGE and iTRAQ as biomarker discovery tools in aquatic toxicology. AB - Molecular approaches in ecotoxicology have greatly enhanced mechanistic understanding of the impact of aquatic pollutants in organisms. These methods have included high throughput Omics technologies, including quantitative proteomics methods such as 2D differential in-gel electrophoresis (DIGE) and isobaric tagging for relative and absolute quantitation (iTRAQ). These methods are becoming more widely used in ecotoxicology studies to identify and characterize protein bioindicators of adverse effect. In teleost fish, iTRAQ has been used successfully in different fish species (e.g. fathead minnow, goldfish, largemouth bass) and tissues (e.g. hypothalamus and liver) to quantify relative protein abundance. Of interest for ecotoxicology is that many proteins commonly utilized as bioindicators of toxicity or stress are quantifiable using iTRAQ on a larger scale, providing a global baseline of biological effect from which to assess changes in the proteome. This review highlights the successes to date for high throughput quantitative proteomics using DIGE and iTRAQ in aquatic toxicology. Current challenges for the iTRAQ method for biomarker discovery in fish are the high cost and the lack of complete annotated genomes for teleosts. However, the use of protein homology from teleost fishes in protein databases and the introduction of hybrid LTQ-FT (Linear ion trap-Fourier transform) mass spectrometers with high resolution, increased sensitivity, and high mass accuracy are able to improve significantly the protein identification rates. Despite these challenges, initial studies utilizing iTRAQ for ecotoxicoproteomics have exceeded expectations and it is anticipated that the use of non-gel based quantitative proteomics will increase for protein biomarker discovery and for characterization of chemical mode of action. PMID- 22056799 TI - Bacterial stress response to environmental radiation relating to the Fukushima radiation discharge event, Japan: will environmental bacteria alter their antibiotic susceptibility profile? AB - Antibiotic resistance in clinical pathogens in humans may be traced back to resistance mechanisms in environmental bacteria and any factors, which are likely to alter (upregulate) resistance in environmental organisms, is of potential and eventual consequence to human pathogens. Furthermore, sublethal doses of gamma radiation to environmental organisms may cause sublethal stress and a selective pressure, which may lead to mutational events that alter the bacterium's susceptibility profile. A gamma (gamma) radiation simulation experiment was performed to emulate the exposure of four environmental bacteria, including Listeria innocua, Bacillus subtilis, E. coli and Pseudomonas aeruginosa, to levels of radiation in and around Fukushima, Japan, equating to 1, 10 and 100 years equivalence exposure. Alteration to susceptibility to 14 antibiotics was measured as the primary endpoint. There was no significant alteration in the susceptibility of the Gram-positive organisms, whereas both Gram-negative organisms became slightly more susceptible to the antibiotics tested over time. These data indicate that such radiation exposure will not increase the antibiotic resistance profile of these organisms and hence not add to the global public health burden of increased antibiotic resistance in human bacterial pathogens. PMID- 22056800 TI - Endocrine-disrupting effects of nonylphenol in the newt, Triturus carnifex (Amphibia, Urodela). AB - The aim of our study was to verify whether environmental concentrations of nonylphenol influenced the adrenal gland of Triturus carnifex. Newts were exposed to 19 MUg/L nominal concentration of nonylphenol throughout the periods of December-January and March-April, corresponding to different stages of the chromaffin cell functional cycle. The morphological features of the steroidogenic and chromaffin tissues, and the serum levels of ACTH, aldosterone, corticosterone, norepinephrine and epinephrine were evaluated. Nonylphenol did not influence ACTH serum levels. During the two periods examined, the steroidogenic tissue had the same reaction: the quantity of cytoplasmic lipids, and the corticosteroid serum levels, decreased, suggesting the inhibition of synthesis and release of corticosteroids. During the two periods examined, the chromaffin tissue reacted differently to nonylphenol. During December-January, the numeric ratio of norepinephrine granules to epinephrine granules, and the epinephrine serum levels, increased, suggesting the stimulation of epinephrine release. During March-April, the numeric ratio of norepinephrine granules to epinephrine granules did not change, and the norepinephrine serum levels decreased, suggesting the inhibition of norepinephrine release. Our results show that nonylphenol influences the activity of the newt adrenal gland; considering the physiological role of this gland, our results suggest that nonylphenol may contribute to amphibian decline. PMID- 22056801 TI - Effects of cadmium chloride and nonylphenol on the expression of StAR-related lipid transfer domain containing protein (START1) gene in aquatic midge, Chironomus riparius. AB - We identified and characterized a partial cDNA of StAR-related lipid transfer domain containing protein gene from Chironomus riparius (CrSTART1) having homology with human MLN64 and Drosophila melanogaster START1 (DmSTART1) and evaluated the effects of cadmium chloride (Cd) and nonylphenol (NP) on its expression. Pfam analysis identified the presence of two StAR-related lipid transfer (START) domains in CrSTART1 having several conserved amino acid residues, characteristic of the MLN64 and DmSTART1. The mRNA expression of CrSTART1 was observed in all developmental stages. The modulation in the mRNA expression of CrSTART1 was investigated after exposure to different concentrations Cd (0, 2, 10, and 20 mg/L) and NP (0, 10, 50, and 100 MUg/L) for different time intervals in fourth instar larvae of C. riparius. Significant downregulation of CrSTART1 mRNA was observed after exposure to 2, 10 and 20 mg/L of Cd for 24, 48 and 72 h. Significant upregulation of CrSTART1 was observed after exposure to 10 and 50 MUg/L of NP for 24, and 48 h period. At 100 MUg/L of NP significant upregulation of CrSTART1 was observed after 12 h and downregulated after 24, 48 and 72 h. PMID- 22056802 TI - TFAM forces mtDNA to make a U-turn. PMID- 22056803 TI - New insights in the mechanism of microRNA-mediated target repression. PMID- 22056808 TI - A minimum principle in codon-anticodon interaction. AB - Imposing a minimum principle in the framework of the so-called crystal basis model of the genetic code, we determine the structure of the minimum set of anticodons which allows the translational-transcription for animal mitochondrial code. The results are in very good agreement with the observed anticodons. PMID- 22056809 TI - An x-ray absorption spectroscopic study of the electronic structure and bonding of rare-earth orthoferrites. AB - Rare-earth orthoferrites, REFeO3 (RE D rare earth; Y), are tremendously adaptable compounds that are being investigated for use in a wide variety of applications including gas sensors, vehicle catalytic converters, and solid-oxide fuel cells. They also exhibit interesting magnetic properties such as high-temperature antiferromagnetism, making them useful for data storage applications. The compounds adopt a distorted perovskite-type structure where the tilt angle of the octahedra increases (Fe-O-Fe bond angle decreases) as the size of the rare-earth atom decreases. Despite intensive study of the physical properties of these compounds, very few studies have investigated how the bonding and electronic structure of these systems change with substitution of the RE. X-ray absorption near-edge spectroscopy (XANES) is a technique well-suited for such a study, and, in view of this, Fe L-, Fe K- and O K-edge spectra from a series of REFeO3 compounds (RE D La, Pr, Nd, Sm, Eu, Gd, Ho, Yb, Y) have been collected, and are presented here. Fe L-edge spectra show that Fe is octahedrally coordinated and that the Fe-centered octahedra do not appear to distort with changes in the identity of the RE. The Fe K-edge spectra contain an intersite hybrid peak, which is an ill-studied feature that is attributed to non-local transitions of 1s electrons to 3d states on the next-nearest-neighbor atom that are hybridized with 4p states on the absorbing atom through O 2p states. In this study, it is shown that the intensity of this feature is strongly dependent on the Fe-O-Fe bond angle; the lower the Fe-O-Fe bond angle, the less intense the intersite hybrid peak is. PMID- 22056810 TI - Comparison of algorithms for out-of-plane artifacts removal in digital tomosynthesis reconstructions. AB - Digital tomosynthesis is a method of limited angle reconstruction of tomographic images produced at variable heights, on the basis of a set of angular projections taken in an arc around human anatomy. Reconstructed tomograms from unprocessed original projection images, however, are invariably affected by tomographic noise such as blurred images of objects lying outside the plane of interest and superimposed on the focused image of the fulcrum plane. The present work investigates the performance of two approaches for generation of tomograms with a reduced noise: a generalised post-processing method, based on constructing a noise mask from all planes in the reconstructed volume, and its subsequent subtraction from the in-focus plane and a filtered Multiple Projection Algorithm. The comparison between the two algorithms shows that the first method provides reconstructions with very good quality in case of high contrast features, especially for those embedded into a heterogeneous background. PMID- 22056811 TI - Capsule endoscopy image analysis using texture information from various colour models. AB - Wireless capsule endoscopy (WCE) is a novel imaging technique that is gradually gaining ground as it enables the non-invasive and efficacious visualization of the digestive track, and especially the entire small bowel including its middle part. However, the task of reviewing the vast amount of images produced by a WCE examination is a burden for the physicians. To tackle this major drawback, an innovative scheme for discriminating endoscopic images related to one of the most common intestinal diseases, ulceration, is presented here. This new approach focuses on colour-texture features in order to investigate how the structure information of healthy and abnormal tissue is distributed on RGB, HSV and CIE Lab colour spaces. The WCE images are pre-processed using bidimensional ensemble empirical mode decomposition so as to facilitate differential lacunarity analysis to extract the texture patterns of normal and ulcerous regions. Experimental results demonstrated promising classification performance (mean accuracy>95%), exhibiting a high potential towards automatic WCE image analysis. PMID- 22056812 TI - Interferon-gamma induces autophagy with growth inhibition and cell death in human hepatocellular carcinoma (HCC) cells through interferon-regulatory factor-1 (IRF 1). AB - Interferon-gamma (IFN-gamma) is a pleiotropic cytokine with immunomodulatory, anti-viral, and anti-proliferative effects. In this study, we examined the effects of IFN-gamma on autophagy and cell growth in human hepatocellular carcinoma (HCC) cells. IFN-gamma inhibited cell growth of Huh7 cells with non apoptotic cell death. IFN-gamma induced autophagosome formation and conversion/turnover of microtubule associated protein 1 light chain 3 (LC3) protein. Furthermore, overexpression of IRF-1 also induced autophagy in Huh7 cells. Silencing IRF-1 expression with target small hairpin RNA blocked autophagy induced by IFN-gamma. Silencing of the autophagy signals Beclin-1 or Atg5 attenuated the inhibitory effect of IFN-gamma on Huh7 cells with decreased cell death. Additionally, IFN-gamma activated autophagy in freshly cultured human HCC cells. Together, these findings show that IFN-gamma induces autophagy through IRF 1 signaling pathway and the induction of autophagy contributes to the growth inhibitory effect of IFN-gamma with cell death in human liver cancer cells. PMID- 22056813 TI - Dual inhibition of (V600E)BRAF and the PI3K/AKT/mTOR pathway cooperates to induce apoptosis in melanoma cells through a MEK-independent mechanism. AB - BRAF is a main oncogene in human melanomas. Here, we show that BRAF depletion by siRNA or inhibition of its activity by treatment with RAF inhibitor Sorafenib induces apoptosis in NPA melanoma cells expressing oncogenic (V600E)BRAF. This effect is mediated through a MEK/ERK-independent mechanism, since treatment with the MEK inhibitor U0126 does not exert any effect. Moreover, we demonstrate that inhibition of the PI3K/AKT/mTOR cascade alone does not increase apoptosis in these cells. However, the blockage of this pathway in cells lacking either BRAF expression or activity cooperates to induce higher levels of apoptosis than those achieved by inhibition of BRAF alone. Consistently, we demonstrate that abrogation of BRAF expression increases AKT and mTOR phosphorylation, suggesting the existence of a compensatory pro-survival mechanism after BRAF depletion. Together, our data provide a rationale for dual targeting of BRAF and PI3K/AKT/mTOR signalling to effectively control melanoma disease. PMID- 22056814 TI - Aura interruption: the Andrews/Reiter behavioral intervention may reduce seizures and improve quality of life - a pilot trial. AB - Patients with epilepsy frequently experience depression and emotional stress and these may function as seizure triggers in epileptogenic frontotemporal cortex, which serves in emotional processing. Eight patients enrolled in a pilot trial of a 6-month epilepsy-specific behavioral approach comprising counseling and relaxation to recognize and eliminate emotional seizure triggers. Potential participants with psychogenic seizures were excluded by long-term EEG and/or the MMPI profile. One participant became seizure free, another had an approximately 90% reduction in seizures, and two additional participants achieved a greater than 50% reduction in seizure frequency (total responder rate=50%), stable during 6 months of observation after the intervention. All completers showed marked and stable improvement of quality of life (Quality of Life in Epilepsy-89 inventory) and temporary improvement in the Profile of Mood States. An adequately powered randomized controlled trial is needed to confirm our findings, which suggest that behavioral approaches may hold promise for motivated patients with epilepsy. PMID- 22056815 TI - Gabapentin and sexual dysfunction: an overlooked and underreported problem? PMID- 22056816 TI - Estimation of the RBE of mammography-quality beams using a combination of a Monte Carlo code with a B-DNA geometrical model. AB - The PENELOPE code is used to determine direct strand break yields corresponding to photons from a (60)Co source and 28 and 30 kV x-ray beams impacting on a B-DNA geometrical model, which accounts for five organizational levels of the human genetic material. Direct single, double and total strand break probabilities are determined in a liquid water homogeneous medium with 1.06 g cm(-3) density. The spectra produced by the x-ray beams at various depths in the phantom have been used to study the dependence of the damage yield on the depth. The relative biological effectiveness (RBE) is also estimated using the (60)Co radiation qualities as the reference. According to this work, the damage probabilities and thus the RBE are, within the uncertainties, similar for both x-ray energies and are independent of the depth into the phantom. Furthermore, the total strand break yield is invariant with respect to the energy of the incident photons. The RBE for low-energy x-ray beams determined here (1.3 +/- 0.1) is lower than that reported by Kellerer, taking into account that he used a 200 kV radiation as the reference quality. However, our RBE values are consistent with those determined by Kuhne et al (2005 Radiat. Res. 164 669-76), which used the same biological endpoint and reference quality as our study. Also, our RBE values are similar to those determined by Verhaegen and Reniers (2004 Radiat. Res. 162 592-9). PMID- 22056817 TI - A model for mitotic inheritance of histone lysine methylation. AB - Histone lysine methylation has been implicated in epigenetic regulation of transcription. Using stable-isotope labelling and quantitative mass spectrometry, we analysed the dynamics of histone lysine methylation. Here we report that histone methylation levels are transiently reduced during S phase and are gradually re-established during subsequent cell cycle stages. However, despite the recovery of overall methylation levels before the next S phase, the methylation levels of parental and newly incorporated histones differ significantly. In addition, histone methylation levels are maintained at steady states by both restriction of methyltransferase activity and the active turnover of methyl groups in cells undergoing an extended G1/S phase arrest. Finally, we propose a 'buffer model' that unifies the imprecise inheritance of histone methylation and the faithful maintenance of underlying gene silencing. PMID- 22056818 TI - AMIGO is an auxiliary subunit of the Kv2.1 potassium channel. AB - Kv2.1 is a potassium channel alpha-subunit abundantly expressed throughout the brain. It is a main component of delayed rectifier current (I(K)) in several neuronal types and a regulator of excitability during high-frequency firing. Here we identify AMIGO (amphoterin-induced gene and ORF), a neuronal adhesion protein with leucine-rich repeat and immunoglobin domains, as an integral part of the Kv2.1 channel complex. AMIGO shows extensive spatial and temporal colocalization and association with Kv2.1 in the mouse brain. The colocalization of AMIGO and Kv2.1 is retained even during stimulus-induced changes in Kv2.1 localization. AMIGO increases Kv2.1 conductance in a voltage-dependent manner in HEK cells. Accordingly, inhibition of endogenous AMIGO suppresses neuronal I(K) at negative membrane voltages. In conclusion, our data indicate AMIGO as a function modulating auxiliary subunit for Kv2.1 and thus provide new insights into regulation of neuronal excitability. PMID- 22056819 TI - Apixaban for stroke prevention in atrial fibrillation: a review of the clinical trial evidence. AB - The objective of this review is to summarize data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trials of apixaban for stroke prevention in patients with atrial fibrillation (AF). The ARISTOTLE trial compared apixaban with warfarin in 18 201 patients with AF and >= 1 additional risk factor for stroke. The AVERROES trial compared apixaban with aspirin in 5599 patients with AF who were at increased risk of stroke and for whom vitamin K antagonists were unsuitable. In ARISTOTLE, apixaban reduced the risk of stroke or systemic embolism by 21% compared with warfarin (1.27% vs 1.60% per year; hazard ratio, 0.79; 95% confidence interval, 0.66-0.95). The reduction was significant and demonstrated the superiority of apixaban over warfarin for the primary outcome of preventing stroke or systemic embolism (P = 0.01 for superiority). Apixaban also reduced all-cause mortality by 11% (P = 0.047) and major bleeding by 31% (P < 0.001) compared with warfarin. The benefits of apixaban observed in ARISTOTLE are further supported by the results from AVERROES, which demonstrated a 55% reduction in the risk of stroke or systemic embolism compared with aspirin. Risk of major bleeding was not significantly different between apixaban and aspirin. Subgroup analyses in both trials demonstrated that the effects of apixaban are highly consistent across various patient subpopulations. Discontinuation of study medication was significantly lower with apixaban than with either warfarin in ARISTOTLE or aspirin in AVERROES. Apixaban is the first new oral anticoagulant that has been shown to be superior to warfarin in reducing stroke or systemic embolism, all cause mortality, and major bleeding in patients with AF. Moreover, in patients with AF who are considered unsuitable for warfarin therapy, apixaban was more effective than aspirin for stroke prevention and had a similar rate of major bleeding. PMID- 22056820 TI - Lone atrial fibrillation: where are we now? AB - There is a growing pandemic of atrial fibrillation (AF), affecting nearly 2% of the general adult population. Atrial fibrillation is commonly associated with structural heart disease, and AF itself causes a sequence of complex processes of electrical, contractile, and structural remodeling of the atrial myocardium, which facilitate further AF progression. Nonetheless, AF may also affect individuals aged <= 65 years who have no evidence of associated cardiopulmonary or other disease, including hypertension; this is otherwise referred to as "lone" AF and is considered to have a generally favorable prognosis. The true prevalence of lone AF is unknown. Growing insights into the diversity of numerous mechanisms involved in the pathogenesis of AF, including acute atrial stretch, structural and electrophysiological alterations, systemic inflammation, oxidative stress, autonomic imbalance, genetic predisposition, and many others, and increasing recognition of novel risk factors for AF, including obesity, metabolic syndrome, subclinical atherosclerosis, sleep apnea, alcohol consumption, and endurance sports, suggest that apparently lone AF might not be so "lone" in many patients, which could have important prognostic and therapeutic implications. In this article, we summarize the current knowledge of epidemiology, etiopathogenesis, and pathophysiology of so-called lone AF and discuss the issues of long-term prognosis and management of patients who have an apparently lone AF. PMID- 22056821 TI - Duration of dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent implantation: a review of the current guidelines and literature. AB - Dual antiplatelet therapy is the mainstay of medical treatment after percutaneous coronary intervention regarding the risk of stent thrombosis occurrence. Since the beginning of the stenting era, antiplatelet regimens have evolved according to the emerging and widespread diffusion of new devices and more challenging indications for their use. In the past years, concerns have been raised about the safety of drug-eluting stent implantation with regard to late and very late stent thrombosis. Thus, the length of dual antiplatelet therapy has been progressively increased with marked individual and local differences. However, prolonged antiplatelet therapy leads to increased risk of bleeding, especially in the setting of surgical procedures, traumas, and/or other diseases. To date, the exact duration of dual antiplatelet therapy after drug-eluting stent implantation is still debated in the literature. The aim of this article is to review the literature and the current guidelines on the risks and benefits of pursuing dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent implantation. PMID- 22056822 TI - Perioperative management of patients receiving anticoagulant or antiplatelet therapy: a clinician-oriented and practical approach. AB - The management of patients who are receiving warfarin, aspirin, clopidogrel, or combinations of these drugs and require their interruption because of an elective surgical or other invasive procedure is a common and sometimes challenging clinical problem. For the practicing clinician, there are 2 key issues for perioperative anticoagulant management: 1) having an approach to stratify patients according to their risk for thromboembolism when warfarin or antiplatelet drug therapy is interrupted, and also having an approach to stratify patients according to the risk of bleeding associated with the surgery or procedure; and 2) determining which patients may require bridging anticoagulation and, if required, how to administer bridging, typically with a low-molecular weight heparin, before and after surgery in a manner that minimizes the risk for bleeding. The overall goal is to minimize patients' risk for thromboembolism and bleeding throughout the perioperative period. The objective of this article is to provide an evidence-based but practical approach relating to these 2 key issues in a manner than can be applied to everyday clinical practice. PMID- 22056823 TI - Review for hospitalists: acute pulmonary embolism. AB - Acute pulmonary embolism (PE) is a common and potentially life-threatening disease; however, the clinical presentation of acute PE can be quite variable, making the diagnosis a challenge. Occlusion of the pulmonary arterial bed can lead to gas exchange abnormalities or right ventricular dysfunction. Mortality rates are high but can be reduced when prompt suspicion leads to accurate diagnosis and treatment. Management includes timely initiation of anticoagulation therapy. The objective of this article is to provide a broad overview of acute PE epidemiology, risk factors, diagnosis, risk stratification, and management. PMID- 22056824 TI - A simulation-based program to train medical residents to lead and perform advanced cardiovascular life support. AB - BACKGROUND: Medical residents are often responsible for leading and performing cardiopulmonary resuscitation; however, their levels of expertise and comfort as leaders of advanced cardiovascular life support (ACLS) teams vary widely. While the current American Heart Association ACLS course provides education in recommended resuscitative protocols, training in leadership skills is insufficient. In this article, we describe the design and implementation in our institution of a formative curriculum aimed at improving residents' readiness for being leaders of ACLS teams using human patient simulation. Human patient simulation refers to a variety of technologies using mannequins with realistic features, which allows learners to practice through scenarios without putting patients at risk. We discuss the limitations of the program and the challenges encountered in implementation. We also provide a description of the initiation and organization of the program. Case scenarios and assessment tools are provided. DESCRIPTION OF THE INSTITUTIONAL TRAINING PROGRAM: Our simulation-based training curriculum consists of 8 simulated patient scenarios during four 1-hour sessions. Postgraduate year-2 and 3 internal medicine residents participate in this program in teams of 4. Assessment tools are utilized only for formative evaluation. Debriefing is used as a teaching strategy for the individual resident leader of the ACLS team to facilitate learning and improve performance. To evaluate the impact of the curriculum, we administered a survey before and after the intervention. The survey consisted of 10 questions answered on a 5-point Likert scale, which addressed residents' confidence in leading ACLS teams, management of the equipment, and management of cardiac rhythms. Respondents' mean presimulation (ie, baseline) and postsimulation (ie, outcome) scores were compared using a 2-sample t test. Residents' overall confidence score improved from 2.8 to 3.9 (P < 0.001; mean improvement, 1.1; 95% confidence interval, 0.7 1.6). The average score for performing and leading ACLS teams improved from 2.8 to 4 (P < 0.001; mean difference, 1.2; 95% confidence interval, 0.7-1.7). There was a uniform increase in the residents' self-confidence in their role as effective leaders of ACLS teams, and residents valued this simulation-based training program. PMID- 22056825 TI - Urinary protein as a marker for systolic blood pressure reduction in patients with type 2 diabetes mellitus participating in an in-hospital diabetes education program. AB - Increased blood pressure (BP) and urinary protein (UP)/microalbuminuria are risk factors for cardiovascular disease in patients with diabetes. Although the management of BP in patients with diabetes should involve a multidisciplinary therapy, there are no reports in which modulators have been identified in an in hospital diabetes education program. The aim of the present study was to investigate the change in BP levels in patients with type 2 diabetes mellitus (T2DM) during a short-term (2-week) in-hospital education program on lifestyle modifications. A total of 167 patients with T2DM (101 men, 66 women; mean age, 61.1 years; glycated hemoglobin, 9.2%) were divided into 2 groups on the basis of their urinary albumin levels: 1 group without UP (urinary albumin level < 30 mg/day) and 1 group with UP (urinary albumin level >= 30 mg/day). We defined efficacy in reducing BP as a 20-mm Hg reduction in systolic BP (SBP) and a 10-mm Hg reduction in diastolic BP, and compared the changes between the 2 groups. Although the group with UP had higher SBP levels than the group without UP at baseline, this difference disappeared at the end of the program. Adjusted multivariate logistic regression analysis showed that UP at baseline was associated with a reduction in SBP (odds ratio, 3.361; 95% confidence interval, 1.29-8.79; P = 0.013). The data suggest that UP may be a marker related to the management of SBP through lifestyle modifications in patients with T2DM. PMID- 22056826 TI - Factors affecting osteoarthritis patients' self-reported goal-directed drug information-seeking behaviors after exposure to direct-to-consumer advertising from physicians and the internet. AB - OBJECTIVE: The objective of this study was to investigate appraisal of means (ie, self-efficacy, outcome expectancy, and affect) in predicting patients' goal directed behaviors of direct-to-consumer advertising (DTCA)-prompted drug information search from physicians and the internet. METHODS: One thousand patients were randomly selected from a nationwide sample frame of 3000 osteoarthritis patients. A self-administered survey assessed exposure to DTCA, drug-information search as goal, self-efficacy, outcome expectancy, affect, and osteoarthritis pain. After 6 weeks, another survey measured the behavior of drug information search for respondents to the first survey. Study subjects were those who were exposed to DTCA in the previous month, and who set drug-information search as their goal. For each information source, a multiple regression analysis was conducted in which drug-information search was the dependent variable, and self-efficacy, outcome expectancy, affect, and osteoarthritis pain were the independent variables. RESULTS: Among 454 patients who were exposed to DTCA, 174 patients set drug-information search as their goal and were the study subjects. The regression for physicians was not statistically significant. The regression for the internet was significant, accounting for 15% of behavior variance. Self efficacy was a strong predictor of goal-directed drug-information search from the internet. CONCLUSIONS: Appraisal of means was useful to predict the goal-directed behavior of DTCA-prompted drug-information search from the internet. For patients who set drug-information search as a goal, actions to promote drug-information search from the internet need to focus on self-efficacy. PMID- 22056827 TI - Severity of obstructive sleep apnea between black and white patients. AB - Obstructive sleep apnea (OSA) is a relatively common problem with potentially serious health consequences. The purpose of this study was to identify whether race has any effect on the severity of OSA. Our hypothesis was that OSA, when present, is more severe in black patients than white patients. This cross sectional study was performed at Truman Medical Centers, a teaching hospital affiliated with University of Missouri-Kansas City School of Medicine (Kansas City, MO). Multiple linear regression analysis was conducted to establish if race was predictive of apnea-hypopnea index (AHI) score when controlling for age, sex, and body mass index. The analysis included 280 patients with complete data for each of the variables in the model. Race (the primary predictor of interest) did not significantly predict AHI score (P = 0.172), and neither did age (P = 0.783). Men had higher AHI scores than women (P < 0.001), and higher body mass index was associated with higher AHI score (P < 0.001). There were more black women in the sample population than white women (P = 0.043). Black patients were also more likely to have hypertension (P = 0.037). This study suggests that race is not a predictor of OSA severity after controlling for age, sex, and body mass index. There is a need for more studies to examine the prevalence of OSA in different races. PMID- 22056828 TI - Transitioning from inpatient to outpatient therapy in patients with in-hospital hyperglycemia. AB - Transition from inpatient to outpatient care for patients with type 2 diabetes mellitus is an important aspect of patient management for which there is no guidance. Intensive glucose lowering with insulin is generally favored for seriously ill hospitalized patients, but after discharge, patients often resume their prior regimens, which may include an array of oral or injected glucose lowering agents. Factors that should be considered in this transition include goals of care/life expectancy, glycated hemoglobin at hospital admission, home medications for other illnesses and their potential for interactions with antidiabetes treatment, comorbidities, nutritional status, physical disabilities, ability to carry out self-monitoring of blood glucose, risk for hypoglycemia, contraindications to oral medications, health literacy, and financial and other resources. Traditional oral therapies that may be used after the patient leaves the hospital include sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, and metformin. alpha-Glucosidase inhibitors are limited by gastrointestinal adverse events, and thiazolidinediones by fluid retention and increased risk for heart failure. Thiazolidinediones also require a long period of administration for onset glucose lowering and are not suitable for transitioning hospitalized patients who have been receiving insulin to outpatient care. Metformin is contraindicated in patients with renal, cardiac, or pulmonary insufficiency. Incretin-based therapies, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, have limited use in hospitals, but may be suitable for the transition to outpatient treatment. The most common adverse events with glucagon-like peptide-1 inhibitors involve the gastrointestinal system. More formal studies of treatment regimens for patients with hyperglycemia leaving the hospital are needed to guide care for this group. PMID- 22056829 TI - A review of recent clinical trials and guidelines on the prevention and management of delirium in hospitalized older patients. AB - Treatment of acute illness in older adults is frequently complicated by the presence of delirium. Delirium is characterized by the development of an altered mental status over the course of hours to days, and can have a fluctuating course. Patients with delirium have difficulty paying attention to their environment, have disorganized thinking, and usually have an altered level of consciousness. While scientists continue to elucidate the pathophysiologic mechanisms associated with delirium, clinicians can identify patients at risk for delirium and diagnose it using valid instruments, such as the Confusion Assessment Method and Confusion Assessment Method for the Intensive Care Unit. Delirium is an independent risk factor for death, institutionalization, and dementia, and resolves in many patients by the time of hospital discharge. For patients admitted to medical units, optimal management of delirium includes reassessment of medications, pain, sleep, nutrition, mobility, need for physical restraints, and bowel and bladder function. The use of antipsychotic medication to sedate delirious patients should be restricted to patients in danger of harming themselves or others and should be used when nonpharmacologic means fail. Multicomponent interventions performed by the hospital care team that address risk factors can prevent delirium in patients in medical units and those undergoing hip fracture repair. This includes attention to the depth of sedation during spinal anesthesia and the addition of regional nerve blocks to patient controlled analgesia in orthopedic patients, both of which may reduce postoperative delirium. Perioperative use of antipsychotics may further reduce the incidence of delirium, although hospital length of stay has not been routinely reduced. Appropriate management of analgesia, sedation, and delirium in the intensive care unit is also associated with reduced duration of mechanical ventilation, as well as intensive care unit and hospital length of stay. The use of dexmedetomidine, an alpha-adrenergic receptor agonist, for sedation may reduce intensive care unit length of stay when compared with use of benzodiazepines. PMID- 22056830 TI - Lung cancer screening: a review of available data and current guidelines. AB - Lung cancer is the leading cause of cancer mortality worldwide. A lack of clinical symptoms in early-stage disease frequently leads to diagnosis at a late stage, and a 15% 5-year survival rate in all patients so diagnosed. This has led to significant interest in effective screening methods to detect early-stage cancers, particularly for high-risk groups, such as current or former smokers. Early clinical trials focused on chest radiograph with or without sputum cytology and failed to show an improvement in mortality with screening. A meta-analysis also failed to show a difference in all-cause mortality. Subsequent protocols compared low-dose computed tomography (LDCT) scan with chest radiograph and documented increased detection of early-stage disease; however, they were not designed to prove a reduction in mortality. The most recent trials have focused on LDCT scans, including the National Lung Screening Trial. Data released from the National Lung Screening Trial demonstrated a statistically significant reduction in lung cancer deaths in patients screened with LDCT scans. When data from the study, including cost-effectiveness, are completely analyzed, they may lead to revision of current lung cancer screening recommendations to include LDCT scans in specific populations at high risk of developing lung cancer. PMID- 22056831 TI - The role of myotubularin-related phosphatases in the control of autophagy and programmed cell death. PMID- 22056832 TI - Memory shaped by age stereotypes over time. AB - OBJECTIVES: Previous studies showed that negative self-stereotypes detrimentally affect the cognitive performance of marginalized group members; however, these findings were confined to short-term experiments. In the present study, we considered whether stereotypes predicted memory over time, which had not been previously examined. We also considered whether self-relevance increased the influence of stereotypes on memory over time. METHOD: Multiple waves of memory performance were analyzed using individual growth models. The sample consisted of 395 participants in the Baltimore Longitudinal Study of Aging. RESULTS: Those with more negative age stereotypes demonstrated significantly worse memory performance over 38 years than those with less negative age stereotypes, after adjusting for relevant covariates. The decline in memory performance for those aged 60 and above was 30.2% greater for the more negative age stereotype group than for the less negative age stereotype group. Also, the impact of age stereotypes on memory was significantly greater among those for whom the age stereotypes were self-relevant. DISCUSSION: This study shows that the adverse influence of negative self-stereotypes on cognitive performance is not limited to a short-term laboratory effect. Rather, the findings demonstrate, for the first time, that stereotypes also predict memory performance over an extended period in the community. PMID- 22056833 TI - Peroxisome proliferator-activated receptor-alpha activation attenuates 3 nitropropionic acid induced behavioral and biochemical alterations in rats: possible neuroprotective mechanisms. AB - Peroxisome proliferators activated receptor is regarded as potential therapeutic targets to control various neurodegenerative disorders. However, none of the study has elucidated its effect in the treatment of Huntington's disease. We explored whether peroxisome proliferators activated receptor-alpha agonist may attenuate various behavioral and biochemical alterations induced by systemic administration of 3-nitropropionic acid (3-NP), an accepted experimental animal model of Huntington's disease phenotype. Intraperitoneal administration of 3-NP (20mg/kg., i.p.) for 4days in rats produced hypolocomotion, muscle incoordination, and cognitive dysfunction. Daily treatment with fenofibrate (100 or 200mg/kg., p.o.), 30min prior to 3-NP administration for a total of 4days, significantly improved the 3-NP induced motor and cognitive impairment. Biochemical analysis revealed that systemic 3-NP administration significantly increased oxidative and nitrosative stress (increase lipid peroxidation, protein carbonyls and nitrite level), lactate dehydrogenase activity whereas, decreased the activities of catalase, superoxide dismutase, reduced glutathione, and succinate dehydrogenase. Fenofibrate treatment significantly attenuated oxidative damage, cytokines and improved mitochondrial complexes enzyme activity in brain. In the present study, MK886, a selective inhibitor of peroxisome proliferators activated receptor-alpha was employed to elucidate the beneficial effect through either receptor dependent or receptor independent neuroprotective mechanisms. Administration of MK886 (1mg/kg, i.p.) prior to fenofibrate (200mg/kg, p.o.) abolished the effect of fenofibrate. The results showed that receptor dependent neuroprotective effects of fenofibrate in 3-NP administered rats provide a new evidence for a role of PPAR-alpha activation in neuroprotection that is attributed by modulating oxidative stress and inflammation. PMID- 22056834 TI - Effect of topical application of mitomycin-C on wound healing in a postlaminectomy rat model: an experimental study. AB - The aim of this study was to investigate the effects of topical application mitomycin-C (MMC) on wound healing after laminectomy. 60 adult male SD rats were equally and randomly divided into five groups. Laminectomy was performed at the level of L1 in all rats. After hemostasis was achieved, cotton pads soaked with saline and MMC (0.1mg/ml, 0.3mg/ml, 0.5mg/ml and 0.7mg/ml) were directly subjected to the exposed dura for 5min in each group. Two weeks after laminectomy all the rats were killed. The vertebral column including the back scar tissue and muscles was obtained to make paraffin sections. The hematoxylin-eosin staining and Masson staining were performed with the obtained paraffin sections. The number of the fibroblast and the capillary density were counted by the hematoxylin-eosin staining slice. The extent of epidural fibrosis and the expression of vascular endothelial growth factor (VEGF) were evaluated by the immunohistochemical slice through a computer image analysis system. Our data showed that the number of fibroblast, capillary density and fibrotic tissue in the 0.5 and 0.7mg/ml MMC groups was significantly lower than the control, 0.1 and 0.3mg/ml MMC groups; while the expression of VEGF in control and 0.1mg/ml MMC groups was notably higher than 0.3, 0.5 and 0.7mg/ml MMC groups. Topical application of MMC above the concentration of 0.3mg/ml could affect all steps of the wound healing process via inhibiting the angiogenesis and fibroblast proliferation, thus delayed the wound healing after laminectomy. PMID- 22056835 TI - Use and limitations of three TRPV-1 receptor antagonists on smooth muscles of animals and man: a vote for BCTC. AB - Specificity of the effect is a crucial factor in using antagonists for detecting the physiological/pathophysiological roles of receptors. Here we examined the capsaicin receptor antagonist effects of three commercially-available substances, capsazepine, iodo-resiniferatoxin (I-RTX) and BCTC, on isolated smooth muscle preparations, including the human intestine. Care was taken to observe possible non-specific effects, to find out safe and effective concentrations. Capsazepine appeared to have a low margin of safety. I-RTX (up to 1MUM) specifically inhibited capsaicin-induced contractions in the guinea-pig ileum and urinary bladder. I-RTX showed agonist activity on the rat urinary bladder. BCTC (1MUM) abolished the contractile effects of capsaicin (1 or 2MUM) on all preparations tested (guinea-pig ileum, bladder, trachea, as well as rat and mouse bladder), and on the guinea-pig renal pelvis, where it failed to influence capsaicin sensitive, sensory neuron-mediated positive inotropy in response to field stimulation. On human intestinal preparations BCTC prevented the relaxant effect of capsaicin. It is concluded that of the three antagonists tested BCTC seems the safest one for inhibiting TRPV-1 receptors. The effect of capsazepine may be complicated by non-specific inhibition of smooth muscle contractility and that of I-RTX by agonist activity. The "local efferent" function of capsaicin-sensitive sensory neurons is not influenced by BCTC, as shown by the results obtained in the renal pelvis. In conclusion, of the TRPV-1 receptor antagonists studied, BCTC (1MUM) seems the most reliable in isolated organ experiments. This substance is also effective in the human intestine. PMID- 22056836 TI - Stimulus-specific blockade of nitric oxide-mediated dilatation by asymmetric dimethylarginine (ADMA) and monomethylarginine (L-NMMA) in rat aorta and carotid artery. AB - Previous work on female rat aorta has shown that although monomethylarginine (L NMMA) and asymmetric dimethylarginine (ADMA) each enhance submaximal phenylephrine-induced tone, consistent with blockade of basal nitric oxide activity, neither agent has any major effect on acetylcholine-induced relaxation. The aim of this study was to adopt a variety of different experimental approaches to test the hypothesis that these methylarginines block basal but not agonist stimulated activity of nitric oxide. Basal activity of nitric oxide was assessed by observing the rise in submaximal phenylephrine-induced tone produced by nitric oxide synthase (NOS) inhibitors in male and female aorta and female carotid artery, and by monitoring the vasodilator actions of superoxide dismutase (SOD) or the PDE 5 inhibitor, T-0156. Agonist-stimulated activity of nitric oxide was assessed by observing the relaxant actions of acetylcholine or calcium ionophore A23187. L-NMMA, ADMA and L-NAME (100 MUM) each enhanced submaximal phenylephrine induced tone and inhibited SOD- or T-0156-induced relaxation, consistent with each NOS inhibitor blocking basal nitric oxide activity. In contrast, L-NMMA and ADMA had little effect on acetylcholine- or A23187-induced relaxation, while L NAME produced powerful blockade. These observations provide support for the hypothesis that L-NMMA and ADMA selectively block basal over agonist-stimulated activity of nitric oxide in rat vessels. PMID- 22056837 TI - Azithromycin fails to reduce inflammation in cystic fibrosis airway epithelial cells. AB - Cystic fibrosis is a hereditary disease caused by a mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene that encodes a chloride (Cl(-)) channel. Cystic fibrosis pulmonary pathophysiology is characterised by chronic inflammation and bacterial infections. Azithromycin, a macrolide antibiotic, has shown promising anti-inflammatory properties in some inflammatory pulmonary diseases. Moreover, all clinical studies have presented an improvement of the respiratory condition of cystic fibrosis patients, but the molecular and cellular mechanisms remain unknown. The aim of this study was to investigate, in bronchial epithelial cells, the effects of azithromycin on inflammatory pathways involved in cystic fibrosis. We have analysed the effects of azithromycin on cystic fibrosis and non-cystic fibrosis bronchial epithelial cell lines but also in non-immortalized non-cystic fibrosis human glandular cells. To create an inflammatory context, cells were treated with Tumor Necrosis Factor (TNF)-alpha or Interleukin (IL)1-beta. Activation of the NF-kappaB pathway was investigated by luciferase assay, western blotting, and by Forster Resonance Energy Transfer imaging, allowing the detection of the interaction between the transcription factor and its inhibitor in live cells. In all conditions tested, azithromycin did not have an anti-inflammatory effect on the cystic fibrosis human bronchial epithelial cells and on CFTR-inhibited primary human bronchial glandular cells. More, our data showed no effect of azithromycin on IL-1beta- or TNF-alpha-induced IL-8 secretion and NF-kappaB pathway activation. Taken together, these data show that azithromycin is unable to decrease in vitro inflammation in cystic fibrosis cells from airways. PMID- 22056838 TI - The interactions of atorvastatin and fluvastatin with carbamazepine, phenytoin and valproate in the mouse maximal electroshock seizure model. AB - The aim of this study was to determine the influence of acute (single) and chronic (once daily for 7 consecutive days) treatments with atorvastatin and fluvastatin on the anticonvulsant potential of three antiepileptic drugs: carbamazepine, phenytoin and valproate in the mouse maximal electroshock-induced seizure model. Additionally, the effects of acute and chronic administration of both statins on the adverse effect potential of three antiepileptic drugs were assessed in the chimney test (motor performance) and passive avoidance task (long term memory). To evaluate the pharmacokinetic characteristics of interaction between antiepileptic drugs and statins, the total brain concentrations of antiepileptic drugs were estimated with the fluorescence polarization immunoassay technique. Results indicate that atorvastatin at doses up to 80mg/kg in chronic experiment attenuated the anticonvulsant potential of carbamazepine by increasing its ED(50) value against maximal electroconvulsions. Acute fluvastatin (80mg/kg) enhanced the anticonvulsant potential of carbamazepine and valproate by decreasing their ED(50) values. Acute fluvastatin (80mg/kg) also markedly increased the total brain carbamazepine concentration by 61% in a pharmacokinetic reaction. Atorvastatin (acute and chronic) and fluvastatin (chronic) in combinations with valproate impaired long-term memory in mice. Both statins in combinations with all three antiepileptic drugs had no impact on their adverse effects in the chimney test. Based on this preclinical study, one can conclude that chronic administration of atorvastatin reduces the anticonvulsant action of carbamazepine and acute fluvastatin can enhance the anticonvulsant potency of the carbamazepine and valproate. The former interaction was pharmacokinetic in nature. PMID- 22056839 TI - Depressive symptoms and diet: their effects on prospective inflammation levels in the elderly. AB - It has been reported that a Mediterranean-type diet in old age is protective against inflammation in Italians with depressive symptoms. In the present study, we explore this hypothesis in a non-Mediterranean, elderly sample, and further disentangle whether it is a Mediterranean diet per se or a healthy diet, in general, that confers this protective effect. The sample is a cohort of people born in 1936, who were assessed on diet and depressive symptoms at age 70. Inflammatory markers, C-reactive protein, fibrinogen and albumin, were collected at ages 70 and 73, while Interleukin-6 transferrin and ferritin were measured at the second time-point only. Controlling for confounding factors (e.g., CVD risk factors, medication) no interaction effect of depressive symptoms and Mediterranean diet was observed on inflammation. However, a main effect of Mediterranean diet on change in C-reactive protein was significant (beta=-0.10, p=0.03), and so too was an effect of the 'Health Aware' diet on ferritin (beta= 0.12, p=0.02). An interaction between depressive symptoms and a Health Aware diet on transferrin levels showed that there was an association between increased depressive symptoms and inflammation in those following a Health Aware diet. Our results indicate that there are advantages of a Mediterranean diet over a Health Aware diet with respect to the progression of inflammation in old age and that depressive symptoms compound inflammatory burden only for specific biomarkers and under specific dietary conditions unrelated to the Mediterranean diet. PMID- 22056840 TI - New insights on the molecular features and electrophysiological properties of dinotefuran, imidacloprid and acetamiprid neonicotinoid insecticides. AB - Structural features and hydrogen-bond interactions of dinotefuran (DIN), imidacoloprid (IMI) and acetamiprid (ACE) have been investigated experimentally through analyses of new crystal structures and observations in structural databases, as well as by Density Functional Theory quantum chemical calculations. Several conformations are observed experimentally in the solid state, highlighting the large flexibility of these compounds. This feature is confirmed by the theoretical calculations in the gas phase, the numerous and different energetic minima of the three neonicotinoids being located within a 10kJ/mol range. Comparisons of the observed and simulated data sheds light on the hydrogen bond (HB) strength of the functional group at the tip of the electronegative fragment of each pharmacophore (NO(2) for DIN and IMI and CN for ACE). This effect originates in the 'push-pull' nature of these fragments and the related extensive electron delocalization. Molecular electrostatic potential calculations provide a ranking of the two fragments of the three neonicotinoid in terms of HB strength. Thus, the NO(2) group of DIN is the strongest HB acceptor of the electronegative fragment, closely followed by the cyano group of ACE. These two groups are significantly more potent than the NO(2) group of IMI. With respect to the other fragments of the three neonicotinoids, the nitrogen atom of the pyridine of IMI and ACE are stronger HB acceptors than the oxygen atom of the furanyl moiety of DIN. Finally, compared to electrophysiological studies obtained from cockroach synaptic and extrasynaptic receptors, DIN appears more effective than IMI and ACE because it strongly increases dose-dependently the ganglionic depolarisation and the currents amplitudes. These data suggest that DIN, IMI and ACE belong to two subgroups which act differently as agonists of insect nicotinic receptors. PMID- 22056841 TI - Treatment of psoriatic nails with indigo naturalis oil extract: a non-controlled pilot study. AB - BACKGROUND: In the treatment of nail psoriasis, standardized therapeutic regimens are currently lacking. OBJECTIVE: To evaluate the therapeutic efficacy of indigo naturalis oil extract in patients with nail psoriasis. METHODS: Patients with nail psoriasis applied indigo naturalis oil extract on affected nails twice daily for 24 weeks. Efficacy was evaluated using the Nail Psoriasis Severity Index (NAPSI) and modified target NAPSI for the single most severely affected nail. RESULTS: Twenty-eight out of 32 patients completed the study. The mean NAPSI was 36.1 +/- 14.7 at baseline and decreased to 14.9 +/- 11.1 at week 24 while the mean modified target NAPSI was 11.7 +/- 3.9 at baseline and decreased to 3.6 +/- 3.2 at week 24. CONCLUSIONS: Indigo naturalis oil extract appeared to improve nail psoriasis. Although preliminary, these results indicate that it could provide a novel therapeutic option for nail psoriasis, a disease notoriously difficult to treat. PMID- 22056842 TI - Cognitive dysfunction in Tunisian LRRK2 associated Parkinson's disease. AB - BACKGROUND: Cognitive impairment and dementia are frequent and debilitating features associated with idiopathic Parkinson's disease (PD). However the prevalence and the pattern of these complications are lacking for LRRK2 (leucine rich kinase 2)-associated PD patients. PURPOSE: The purpose of this study was to assess cognitive function in LRRK2- associated PD patients. MATERIAL AND METHODS: 55 patients diagnosed with PD-related LRRK2 G2019S mutation were included in the study and compared to the same number of G2019S non-carriers PD patients. Age, sex, disease duration, the movement disorder society-unified Parkinson's Disease rating scale (MDS-UPDRS), Hoehn and Yahr stage, Schwab and England scale and the 30-item geriatric depression scale (GDS) scores were noted. Cognitive assessment included MMSE (Mini-Mental Examination), MOCA (Montreal Cognitive Assessment) and FAB (Frontal Assessment Battery). RESULTS: MMSE, MOCA and FAB performance in G2019S carriers PD patients was similar to that of non-carriers. In both groups, performance was primarily impaired on visuospatial and executive tasks. Cognitive impairment was associated with older age, lower educational level and increased severity of motor impairment. CONCLUSION: Cognitive functions were similarly affected in PD patients with and without LRRK2 G2019S mutation with mainly impaired visuospatial and executive abilities. However, these results need to be confirmed by further large and prospective studies. PMID- 22056843 TI - Importance of ambulatory blood pressure monitoring in adolescent hypertension. AB - There has been a steady increase in the prevalence of adolescent hypertension in recent years. In order to prevent target organ damages, it is important to determine the group of hypertensive adolescents. If repeatedly elevated blood pressure values are observed, with special emphasis on white coat hypertension, which is particularly frequent at this age, ambulatory blood pressure monitoring is highly recommended before pharmacological treatment is started. In addition, performing ambulatory blood pressure monitoring is recommended with target organ damage, resistance to therapy, and suspicion of secondary hypertension. The results of the widely available, simple-to-use device are easy to reproduce. PMID- 22056844 TI - Heart failure nurses play a pivotal role in linking clinical research to clinical practice: translational research. PMID- 22056845 TI - Porcine circovirus type 2 (PCV2) infections: clinical signs, pathology and laboratory diagnosis. AB - Clinical signs and pathological features are still the corner-stones to suspect and diagnose overt disease associated with PCV2 infection. The clinico pathological scope of this viral infection has been expanded over time. From the initial description of postweaning multisystemic wasting syndrome, some enteric, respiratory and reproductive disorders have been subsequently linked with PCV2. Porcine dermatitis and nephropathy syndrome, an immunocomplex disease, has also been associated with infection by this virus. All together, these conditions have been grouped under the name of porcine circovirus diseases (PCVD) or porcine circovirus associated diseases (PCVAD). The precise mechanisms by which a PCV2 infected pig develops a PCV2 subclinical infection or a clinical PCVD/PCVAD are still to be fully elucidated, but inferences based upon clinical, gross and histologic findings from field cases of disease have been useful to suggest the pathogenesis of this viral infection. The objective of the present review is to update the current knowledge on the clinical and pathological scope of PCV2 infections, as well as on their diagnosis. Moreover, a proposal on a unified PCVD/PCVAD terminology and clearly defined diagnostic criteria for these conditions are also given. PMID- 22056846 TI - Tripping over emerging pathogens around the world: a phylogeographical approach for determining the epidemiology of Porcine circovirus-2 (PCV-2), considering global trading. AB - Porcine circovirus-2 (PCV-2) is an emerging virus associated with a number of different syndromes in pigs known as Porcine Circovirus Associated Diseases (PCVAD). Since its identification and characterization in the early 1990s, PCV-2 has achieved a worldwide distribution, becoming endemic in most pig-producing countries, and is currently considered as the main cause of losses on pig farms. In this study, we analyzed the main routes of the spread of PCV-2 between pig producing countries using phylogenetic and phylogeographical approaches. A search for PCV-2 genome sequences in GenBank was performed, and the 420 PCV-2 sequences obtained were grouped into haplotypes (group of sequences that showed 100% identity), based on the infinite sites model of genome evolution. A phylogenetic hypothesis was inferred by Bayesian Inference for the classification of viral strains and a haplotype network was constructed by Median Joining to predict the geographical distribution of and genealogical relationships between haplotypes. In order to establish an epidemiological and economic context in these analyses, we considered all information about PCV-2 sequences available in GenBank, including papers published on viral isolation, and live pig trading statistics available on the UN Comtrade database (http://comtrade.un.org/). In these analyses, we identified a strong correlation between the means of PCV-2 dispersal predicted by the haplotype network and the statistics on the international trading of live pigs. This correlation provides a new perspective on the epidemiology of PCV-2, highlighting the importance of the movement of animals around the world in the emergence of new pathogens, and showing the need for effective sanitary barriers when trading live animals. PMID- 22056847 TI - The influence of HLA alleles and HBV subgenotyes on the outcomes of HBV infections in Northeast China. AB - Hepatitis B virus (HBV) infection has a wide variety of clinical outcomes, it could be spontaneouly recovered and also could develop fulminant liver failure or cirrhosis with hepatocellular carcinoma. Human leukocyte antigen (HLA) polymorphism and HBV (sub)genotypes have been speculated to associate with the outcome of HBV infection because the data obtained from various populations who bear different HLA alleles have shown a HLA polymorphism associated outcome of HBV infection. However, as the most important viral and host genetic factors, the impact of HBV (sub)genotypes in combination with HLA polymorphism on the clinical outcomes of HBV infections remains unclear. To demonstrate the association of HLA allele polymorphism in combination with HBV subgenotypes with the outcome of HBV infection in Northeastern Han Chinese population, a total of 230 HBV-infected individuals (Infection group) were compared to 210 random selected controls (Control group) who are negative for HBV infection for their HLA alleles frequency as well as the associations with the virus infection, clearance and persistence in combination with HBV subgenotypes. Of the 230 HBV-infected subjects, 54 were acute self-limited hepatitis (ASH) with HBV subgenotype C2 (ASH C2), 144 were chronic hepatitis (CH) with HBV subgenotype C2 and B2 (CH-C2 and CH B2), and 32 were spontaneously recovered (SR) without subgenotype results. When two groups are compared, the results suggest that B*48, B*51 and DRB1*12 carrier may have a high risk for HBV infection, but B*51 is likely association with spontaneous recovery and DRB1*07, 12 may be implied in viral persistence. HLA B*15, DRB1*11 and 14 associated with viral clearance in the cases of HBV-C2 infection; HLA-B*54 carriers in chronic group are more sensitive to with the infection of HBV subgenotype B2; HLA-B*07 and DRB1*13 may protect subjects from HBV infection. The data presented a link between HLA polymorphism and HBV pathogenesis and suggested potential therapeutic targets for hepatitis B. PMID- 22056848 TI - Functional characterization of EUL47 in productive replication, morphogenesis and infectivity of equine herpesvirus 1. AB - EUL47 is a major component of the tegument of equine herpesvirus 1 (EHV-1). To determine its function, we used Red/ET cloning to delete its gene (gene 13) from EHV-1 strain Ab4p inserted into a bacterial artificial chromosome (BAC), yielding Ab4pattBDelta13. We also examined the reverted virus (Ab4pattB13R). Ab4pattBDelta13 replicated in rabbit kidney (RK)-13 cells, indicating that ORF13 is dispensable for virus replication in cell culture. Its intracellular and extracellular titers were about 10- and 100-fold lower than those of the revertant and parent strains, respectively. In addition, the plaque size was half the plaque sizes of the other two strains. The particle-to-plaque forming unit ratio of Ab4pattBDelta13 was 21-fold greater than the ratios of the revertant and parent strains. No enveloped virions were detected in the cytoplasm of Ab4pattBDelta13-infected cells by transmission electron microscopy. In hamster, Ab4pattBDelta13 caused clinical signs and weight loss after only 1 day, but induced less severe neurological signs than did the revertant and parent strains. These results indicate that EUL47 is structurally required for normal virus replication, viral morphogenesis and viral infectivity, and that loss of EUL47 moderately attenuates the neuropathogenicity of EHV-1 in the hamster model. PMID- 22056850 TI - Bevacizumab-induced laryngeal necrosis. PMID- 22056851 TI - Sorafenib-induced diarrhea and hypophosphatemia: mechanisms and therapeutic implications. PMID- 22056852 TI - Prognostic significance of UBE2C mRNA expression in high-risk early breast cancer. A Hellenic Cooperative Oncology Group (HeCOG) Study. AB - BACKGROUND: The ubiquitin-proteasome system (UPS) plays a pivotal role in tumorigenesis. Components of the UPS have recently been implicated in breast cancer progression. In the present study, we sought to explore the prognostic and/or predictive significance of UBE2C messenger RNA (mRNA) expression on disease-free survival (DFS) and overall survival (OS) in high-risk operable breast cancer patients. METHODS: Five hundred and ninety-five high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative, dose dense sequential chemotherapy with epirubicin followed by CMF (cyclophosphamide, methotrexate and 5-fluorouracil) with or without paclitaxel (Taxol). RNA was extracted from 313 formalin-fixed primary tumor tissue samples followed by one step quantitative RT-PCR for assessment of mRNA expression of UBE2C. RESULTS: High UBE2C mRNA expression was associated with poor DFS (Wald's P = 0.003) and OS (Wald's P = 0.005). High tumor grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of UBE2C. Results of the Cox multivariate regression analysis revealed that high UBE2C mRNA expression remained an independent adverse prognostic factor for relapse (P = 0.037) and death (P = 0.05). CONCLUSIONS: High UBE2C mRNA expression was found to be of adverse prognostic significance in high-risk breast cancer patients. These findings need to be validated in larger cohorts. PMID- 22056853 TI - Importance of gender in diffuse malignant peritoneal mesothelioma. AB - BACKGROUND: Combined therapy involving cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy has been shown to improve survival outcomes for patients with diffuse malignant peritoneal mesothelioma (DMPM). The present study aims to investigate gender as a potential prognostic factor on overall survival. PATIENTS AND METHODS: Over a period of two decades, 294 patients who underwent CRS and perioperative intraperitoneal chemotherapy were selected from a large multi-institutional registry to assess the prognostic significance of gender on overall survival. RESULTS: Female patients were shown to have a significantly improved survival outcome than male patients (P < 0.001). Staging according to a recently proposed tumor-node-metastasis categorization system was significant in both genders. Older female patients had significantly worse survival than younger female patients (P = 0.019), a finding that was absent in male patients. Female patients with low-stage disease were found to have a very favorable long-term outcome after combined treatment. CONCLUSIONS: Gender has demonstrated a significant impact on overall survival for patients with DMPM after CRS and perioperative intraperitoneal chemotherapy. An improved understanding of the role of estrogen in the pathogenesis of DMPM may improve the prognostication of patients and determine the role of adjuvant hormonal treatment in the future. PMID- 22056854 TI - Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial. AB - BACKGROUND: The cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown. PATIENTS AND METHODS: Women with resected node-positive or intermediate-risk node negative HER2 overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF)>=55% were randomized (1:2) to doxorubicin 60 mg/m2 (A)+cyclophosphamide 600 mg/m2 (C) every 21 days (q21d) for four cycles or PLD 35 mg/m2+C q21d+trastuzumab 2 mg/kg weekly (H) for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m2 with H for 12 weeks followed by H to complete 1 year. The primary end point was cardiac event rate or inability to administer 1 year of trastuzumab. RESULTS: Of 181 randomized patients, 179 underwent cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to cardiotoxicity was 18.6% [n=11; 95% confidence interval (CI) 9.7% to 30.9%] with A+C->T+H and 4.2% (n=5; 95% CI 1.4% to 9.5%) with PLD+C+H->T+H (P=0.0036). All events, except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P=0.0014). CONCLUSION: PLD+C+H->T+H is feasible and results in lower early cardiotoxicity rates compared with A+C->T+H. PMID- 22056855 TI - Predicting and managing the risk of pulmonary haemorrhage in patients with NSCLC treated with bevacizumab: a consensus report from a panel of experts. AB - BACKGROUND: Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. Severe pulmonary haemorrhage (PH) is a rare but serious potential adverse event associated with bevacizumab therapy for advanced non-squamous non small-cell lung cancer (NSCLC). METHODS: A panel of expert oncologists, pulmonologists and radiologists reviewed the available data to identify predictive factors for PH in order to help guide physicians using bevacizumab in patients with NSCLC. RESULTS: Patients with NSCLC are at an increased risk of PH owing to the underlying disease process. Patients with squamous histology and/or a history of grade >= 2 haemoptysis (>= 2.5 ml per event) should not receive bevacizumab. No clinical or radiological features (including cavitation and central tumour location) reliably predict severe PH in bevacizumab-treated patients. Major blood vessel infiltration and bronchial vessel infiltration, encasement and abutting may predict PH; however, standardised radiological criteria for defining infiltration have not been established. Eligibility for bevacizumab is not affected by patient age, performance status or anticoagulation or antiplatelet therapy. CONCLUSIONS: An individualised risk-benefit assessment should be undertaken in all patients with NSCLC in whom bevacizumab is being considered. Further research is required to elucidate the mechanisms underlying PH and the clinical risk factors. PMID- 22056856 TI - Dosimetric evaluation of breast radiotherapy in a dynamic phantom. AB - This phantom study quantifies changes in delivered dose due to respiratory motion for four breast radiotherapy planning techniques: three intensity-modulated techniques (forward-planned, surface-compensated and hybrid intensity-modulated radiation therapy (IMRT)); using a combination of open fields and inverse planned IMRT) and a 2D conventional technique. The plans were created on CT images of a wax breast phantom with a cork lung insert, and dose distributions were measured using films inserted through slits in the axial and sagittal planes. Films were irradiated according to each plan under a static (modeling breathhold) and three dynamic conditions--isocenter set at mid-respiratory cycle with motion amplitudes of 1 and 2 cm and at end-cycle with 2 cm motion amplitude (modeling end-exhale). Differences between static and moving deliveries were most pronounced for the more complex planning techniques with hot spots of up to 107% appearing in the anterior portion of all three IMRT plans at the largest motion at the end-exhale set-up. The delivered dose to the moving phantom was within 5% of that to the static phantom for all cases, while measurement accuracy was +/-3%. The homogeneity index was significantly decreased only for the 2 cm motion end-exhale set-up; however, this same motion increased the equivalent uniform dose because of improved posterior breast coverage. Overall, the study demonstrates that the effect of respiratory motion is negligible for all planning techniques except in occasional instances of large motion. PMID- 22056857 TI - Electronic structure and energetics of tetragonal SrCuO2 and its high-pressure superstructure phase. AB - First-principles calculations have been used to investigate the electronic structure and energetics of the simple tetragonal SrCuO2 (P4=mmm) and its high pressure tetragonal superstructure (P4=mmm). Based on the calculations, the high pressure phase is metastable as compared with the low pressure tetragonal phase, with an energy difference of 0.13 eV per SrCuO2 formula unit. The energy barrier to the transition from the superstructure to the simple tetragonal structure is 0.24 eV at 7 GPa; thus, high temperatures are required to synthesize the latter. Among the possible structural configurations resulting from the partially occupied oxygen site in the superstructure phase, the most stable structure has a space group PN4m2, reduced from that of the simple tetragonal structure P4=mmm. The detailed analysis of the electronic band structures of the simple tetragonal and superstructure phases suggests that the out-of-plane buckling of the O atoms in the superstructure leads to significant decrease in the O p-Cu d orbital overlap, allowing the energy of the system to be lowered, which is necessary for the structural stability. An understanding of the electronic structure and energetics of the high-pressure superstructure phase and its relation to the simple tetragonal phase provides a basis for exploring the physical properties of the infinite layer, high-TC superconductor. PMID- 22056858 TI - Isolated eyelid edema in Melkersson-Rosenthal syndrome: a case series. AB - PURPOSE: To report the clinicopathologic features of a series of patients with Melkersson-Rosenthal syndrome (MRS). METHODS: Patients in this clinicopathological case series were identified through retrospective review. Five Caucasian patients (2 women and 3 men; age range, 46 to 73 years) with isolated eyelid swelling presented over an 11-month period to two Canadian tertiary Oculoplastic referral centres. All underwent clinical examination and had tissue biopsies. RESULTS: The patients presented with non-pitting, non pruritic, painless and recurrent eyelid swelling. None had evidence of cranial nerve palsy or fissured tongue. The duration of symptoms before referral was between 1-5 years. Histopathological examination showed granulomatous inflammation in four patients. Granulomatous folliculitis was a novel finding in three patients. CONCLUSIONS: Monosymptomatic patients with MRS require a high index of suspicion. Histopathological confirmation is vital for the diagnosis. PMID- 22056860 TI - Retinopathy in a patient with Fanconi anemia and vitamin B12 deficiency. PMID- 22056861 TI - Trabeculectomy pearls of wisdom; mitomycin-soaked pledget 'necklace' suture. PMID- 22056862 TI - Comment on 'Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab'. PMID- 22056864 TI - Central serous chorioretinopathy following oral tadalafil. PMID- 22056865 TI - A day at the races: ocular injuries in extreme motorcycle racing spectators. PMID- 22056867 TI - New concept: treating nonproliferative diabetic retinopathy with light adaptation of rods during sleep. PMID- 22056868 TI - TGFBI-linked corneal dystrophies treated using superficial lamellar keratectomy combined with phototherapeutic keratectomy. PMID- 22056869 TI - Authorship and the role of medical writers. PMID- 22056870 TI - In vivo confocal microscopic evaluation of keratic precipitates and endothelial morphology in Fuchs' uveitis syndrome. AB - PURPOSE: To evaluate the endothelial cell layer in patients with Fuchs' uveitis syndrome (FUS) with respect to the type and distribution of keratic precipitates (KP), endothelial cell morphology, and endothelial cell density (ECD), using in vivoconfocal microscopy (IVCM). METHODS: Forty eyes of 40 patients (mean age of 32.2 +/- 12.5 years) with the clinical diagnosis of FUS were evaluated with IVCM (Confoscan 3.0, Vigonza, Italy). KP were classified as type I (small, round), type II (stippled), type III (dendritiform), and type IV (globular). When >1 KP type was present, differentiation between the predominant and less frequent KP was made as 'primary' and 'secondary'. ECD was measured and compared with age matched 60 control subjects. Endothelial blebs were classified as small (3-10 MUm) or large (>10 MUm). RESULTS: In 36 (90.0%) cases with FUS, more than one KP type was observed with IVCM. Type III (dendritiform) KP was the most frequently observed primary KP type (85.0%), followed by type II (stippled) KP (15.0%). Secondary KP included type II (58.3%), type IV (globular) (27.8%), and type III (13.9%). The mean endothelial cell density of eyes with FUS (2588 +/- 396 cells/mm(2)) was significantly lower than that of control subjects (2930 +/- 364 cells/mm(2)) (t-test; P<0.001). Eyes with FUS had lower proportion of hexagonal cells and higher percentage of polymegethism compared with the uninvolved contralateral eyes. Endothelial blebs (21 small, 16 large blebs) were observed in 37 (92.5%) eyes. CONCLUSIONS: FUS is characterized by dendritiform KP and is associated with decreased ECD and altered endothelial cell morphology. PMID- 22056871 TI - Molecular epidemiology of adrenocortical tumors in southern Brazil. AB - The high frequency of TP53 R337H carriers in southern Brazil is responsible for the highest known incidence of childhood adrenocortical tumor (ACT). Our aims were to examine other contributing mutations, age-related risk factors, epidemiological differences in ACT and to shed light on a method for increasing the survival rate of children. The fetal zone of the adrenal cortex is believed to be one of the tissues most susceptible to adenoma or carcinoma formation due to loss of p53 function. The founder germline R337H mutation is found in 95% of ACTs of young children, a much greater proportion than in adults. Despite intense educational campaigns about the high incidence of ACT in Parana State, advanced cases remain common. Four advanced ACT cases (4/5) were admitted to a single institution in the first 6months of 2011 in Parana State, none of the families knew about ACT, and 2 reported no familial cancer syndrome. Curative resection is possible when a small ACT is detected early. PMID- 22056872 TI - Twist contributes to hormone resistance in breast cancer by downregulating estrogen receptor-alpha. AB - The role of estrogen receptor-alpha (ER) in breast cancer development, and as a primary clinical marker for breast cancer prognosis, has been well documented. In this study, we identified the oncogenic protein, TWIST1 (Twist), which is overexpressed in high-grade breast cancers, as a potential negative regulator of ER expression. Functional characterization of ER regulation by Twist was performed using Twist low (MCF-7, T-47D) and Twist high (Hs 578T, MDA-MB-231, MCF 7/Twist) expressing cell lines. All Twist high expressing cell lines exhibited low ER transcript and protein levels. By chromatin immunoprecipitation and promoter assays, we demonstrated that Twist could directly bind to E-boxes in the ER promoter and significantly downregulate ER promoter activity in vitro. Functionally, Twist overexpression caused estrogen-independent proliferation of breast cells, and promoted hormone resistance to the selective estrogen receptor modulator tamoxifen and selective estrogen receptor down-regulator fulvestrant. Importantly, this effect was reversible on downregulating Twist. In addition, orthotopic tumors generated in mice using MCF-7/Twist cells were resistant to tamoxifen. These tumors had high vascular volume and permeability surface area, as determined by magnetic resonance imaging (MRI). Mechanistically, Twist recruited DNA methyltransferase 3B (DNMT3B) to the ER promoter, leading to a significantly higher degree of ER promoter methylation compared with parental cells. Furthermore, we demonstrated by co-immunoprecipitation that Twist interacted with histone deacetylase 1 (HDAC1) at the ER promoter, causing histone deacetylation and chromatin condensation, further reducing ER transcript levels. Functional re-expression of ER was achieved using the demethylating agent, 5 azacytidine, and the HDAC inhibitor, valproic acid. Finally, an inverse relationship was observed between Twist and ER expression in human breast tumors. In summary, the regulation of ER by Twist could be an underlying mechanism for the loss of ER activity observed in breast tumors, and may contribute to the generation of hormone-resistant, ER-negative breast cancer. PMID- 22056873 TI - Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum. AB - Pancreatic cancer remains as one of the most deadly cancers, and responds poorly to current therapies. The prognosis is extremely poor, with a 5-year survival of less than 5%. Therefore, search for new effective therapeutic drugs is of pivotal need and urgency to improve treatment of this incurable malignancy. Synthetic alkyl-lysophospholipid analogs (ALPs) constitute a heterogeneous group of unnatural lipids that promote apoptosis in a wide variety of tumor cells. In this study, we found that the anticancer drug edelfosine was the most potent ALP in killing human pancreatic cancer cells, targeting endoplasmic reticulum (ER). Edelfosine was taken up in significant amounts by pancreatic cancer cells and induced caspase- and mitochondrial-mediated apoptosis. Pancreatic cancer cells show a prominent ER and edelfosine accumulated in this subcellular structure, inducing a potent ER stress response, with caspase-4, BAP31 and c-Jun NH(2) terminal kinase (JNK) activation, CHOP/GADD153 upregulation and phosphorylation of eukaryotic translation initiation factor 2 alpha-subunit that eventually led to cell death. Oral administration of edelfosine in xenograft mouse models of pancreatic cancer induced a significant regression in tumor growth and an increase in apoptotic index, as assessed by TUNEL assay and caspase-3 activation in the tumor sections. The ER stress-associated marker CHOP/GADD153 was visualized in the pancreatic tumor isolated from edelfosine-treated mice, indicating a strong in vivo ER stress response. These results suggest that edelfosine exerts its pro-apoptotic action in pancreatic cancer cells, both in vitro and in vivo, through its accumulation in the ER, which leads to ER stress and apoptosis. Thus, we propose that the ER could be a key target in pancreatic cancer, and edelfosine may constitute a prototype for the development of a new class of antitumor drugs targeting the ER. PMID- 22056874 TI - Increased vascularity and spontaneous metastasis of breast cancer by hedgehog signaling mediated upregulation of cyr61. AB - The Hedgehog (Hh) pathway is well known for its involvement in angiogenesis and vasculogenesis during ontogeny. The ligand, Sonic Hh (SHH), has an important role in vascular formation during development. However, SHH expression is upregulated on tumor cells and can impact the tumor microenvironment. We have investigated the effects of autocrine as well as paracrine Hh signaling on tumor cells as well as on endothelial cells, respectively. Upon constitutive expression of SHH, breast cancer cells showed aggressive behavior and rapid xenograft growth characterized by highly angiogenic tumors that were spontaneously metastatic. In these cells, SHH caused activation of the Hh transcription factor, GLI1, leading to upregulated expression of the potent pro-angiogenic secreted molecule, CYR61 (cysteine-rich angiogenic inducer 61). Silencing of CYR61 from these SHH expressing Hh activated cells blunted the malignant behavior of the tumor cells and resulted in reduced tumor vasculature and limited hematogenous metastases. Thus, CYR61 is a critical downstream contributor to the Hh influenced pro angiogenic tumor microenvironment. We also observed concomitant upregulation of SHH and CYR61 transcripts in tumors from patients with advanced breast cancer, further ratifying the clinical relevance of our findings. In summary, we have defined a novel, VEGF-independent, clinically relevant, pro-angiogenic factor, CYR61, that is a transcriptional target of Hh-GLI signaling. PMID- 22056875 TI - Cyclin G1 regulates the outcome of taxane-induced mitotic checkpoint arrest. AB - Anti-mitotic chemotherapeutic agents such as taxanes activate the spindle assembly checkpoint (SAC) to arrest anaphase onset, but taxane-exposed cells eventually undergo slippage to exit mitosis. The therapeutic efficacy of taxanes depends on whether slippage after SAC arrest culminates in continued cell survival, or in death by apoptosis. However, the mechanisms that determine these outcomes remain unclear. Here, we identify a novel role for cyclin G1 (CCNG1), an atypical cyclin. Increased CCNG1 expression accompanies paclitaxel-induced, SAC mediated mitotic arrest, independent of p53 integrity or signaling through the SAC component, BUBR1. CCNG1 overexpression promotes cell survival after paclitaxel exposure. Conversely, CCNG1 depletion by RNA interference delays slippage and enhances paclitaxel-induced apoptosis. Consistent with these observations, CCNG1 amplification is associated with significantly shorter post surgical survival in patients with ovarian cancer who have received adjuvant chemotherapy with taxanes and platinum compounds. Collectively, our findings implicate CCNG1 in regulating slippage and the outcome of taxane-induced mitotic arrest, with potential implications for cancer therapy. PMID- 22056876 TI - A retinoic acid receptor RARalpha pool present in membrane lipid rafts forms complexes with G protein alphaQ to activate p38MAPK. AB - Retinoic acid (RA) regulates several gene programs by nuclear RA receptors (RARs) that are ligand-dependent transcriptional transregulators. The basic mechanism for switching on transcription of cognate-target genes involves RAR binding at specific response elements and a network of interactions with coregulatory protein complexes. In addition to these classical genomic effects, we recently demonstrated that RA also induces the rapid activation of the p38MAPK/MSK1 pathway, with characteristic downstream consequences on the phosphorylation of RARs and the expression of their target genes. Here, we aimed at deciphering the underlying mechanism of the rapid non-genomic effects of RA. We highlighted a novel paradigm in which a fraction of the cellular RARalpha pool is present in membrane lipid rafts, where it forms complexes with G protein alpha Q (Galphaq) in response to RA. This rapid RA-induced formation of RARalpha/Galphaq complexes in lipid rafts is required for the activation of p38MAPK that occurs in response to RA. Accordingly, in RA-resistant cancer cells, characterized by the absence of p38MAPK activation, RARalpha present in membrane lipid rafts does not associate with Galphaq, pointing out the essential contribution of RARalpha/Galphaq complexes in RA signaling. PMID- 22056877 TI - Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer. AB - Chitinase 3-like 1 (CHI3L1), one of the mammalian members of the chitinase family, is expressed in several types of human cancer, and elevated serum level of CHI3L1 is suggested to be a biomarker of poor prognosis in advanced cancer patients. However, the overall biological function of CHI3L1 in human cancers still remains unknown. Studies were performed to characterize the role of CHI3L1 in cancer pathophysiology utilizing human colorectal cancer samples and human cell lines. Plasma protein and tissue mRNA expression levels of CHI3L1 in colorectal cancer were strongly upregulated. Immunohistochemical analysis showed that CHI3L1 was expressed in cancer cells, and CHI3L1 expression had a significant association with the number of infiltrated macrophages and microvessel density (MVD). By utilizing transwell migration and tube-formation assays, overexpression of CHI3L1 in SW480 cells (human colon cancer cells) enhanced the migration of THP-1 cells (human macrophage cells) and HUVECs (human endothelial cells), and the tube formation of HUVECs. The knockdown of CHI3L1 by RNA interference or the neutralization of CHI3L1 by anti-CHI3L1 antibody displayed strong suppression of CHI3L1-induced migration and tube formation. Cell proliferation assay showed that CHI3L1 overexpression significantly enhanced the proliferation of SW480 cells. Enzyme-linked immunosorbent assay (ELISA) analysis showed that CHI3L1 increased the secretion of inflammatory chemokines, IL-8 and monocyte chemoattractant protein-1 (MCP-1), from SW480 cells through mitogen activated protein kinase (MAPK) signaling pathway. Both neutralization of IL-8 or MCP-1 and inhibition or knockdown of MAPK in SW480 cells significantly inhibited CHI3L1-induced migration and tube formation. In a xenograft mouse model, overexpression of CHI3L1 in HCT116 cells (human colon cancer cells) enhanced the tumor growth as well as macrophage infiltration and MVD. In conclusion, CHI3L1 expressed in colon cancer cells promotes cancer cell proliferation, macrophage recruitment and angiogenesis. Thus, the inhibition of CHI3L1 activity may be a novel therapeutic strategy for human colorectal cancer. PMID- 22056878 TI - Synergistic antitumor activity of lapatinib and retinoids on a novel subtype of breast cancer with coamplification of ERBB2 and RARA. AB - All-trans retinoic acid (ATRA), the only clinically available cyto differentiating agent, has potential for the therapy/chemoprevention of breast carcinoma. Given the heterogeneous nature of this tumor, a rational use of ATRA and derivatives (retinoids) in the clinic requires the identification of patients that would benefit from retinoid-based protocols. Here, we demonstrate that 23 32% of the human ERBB2(+) breast cancers show coamplification of retinoic acid receptor alpha (RARA), encoding the retinoic acid receptor, RARalpha. This represents a novel subtype of breast cancer characterized by remarkable sensitivity to ATRA and RARalpha agonists, regardless of positivity to the estrogen receptor, a known modulator of retinoid sensitivity. In estrogen receptor-negative cellular models showing coamplification of ERBB2 and RARA, simultaneous targeting of the corresponding gene products with combinations of lapatinib and ATRA causes synergistic growth inhibition, cyto-differentiation and apoptosis. This provides proof-of-principle that coamplification of ERBB2 and RARA can be exploited for the stratified and targeted therapy of a novel subtype of breast cancer patients, with an approach characterized by tumor cell selectivity and low predicted toxicity. The available cellular models were exploited to define the molecular mechanisms underlying the antitumor activity of combinations between lapatinib and ATRA. Global gene expression and functional approaches provide evidence for three components of the antiproliferative/apoptotic responses triggered by lapatinib+ATRA. Induction of the retinoid-dependent RARRES3 protein by ATRA stabilizes the effect of lapatinib inhibiting ERBB2 phosphorylation. Upregulation and activation of the transcription factor FOXO3A integrates ATRA-dependent transcriptional and lapatinib-dependent posttranscriptional signals, controlling the levels of effector proteins like the antiapoptotic factor, BIRC5. Stimulation of the TGFbeta pathway by ATRA mediates other components of the apoptotic process set in motion by simultaneous targeting of ERBB2 and RARalpha. PMID- 22056879 TI - RNAi screening in glioma stem-like cells identifies PFKFB4 as a key molecule important for cancer cell survival. AB - The concept of cancer stem-like cells (CSCs) has gained considerable attention in various solid tumors including glioblastoma, the most common primary brain tumor. This sub-population of tumor cells has been intensively investigated and their role in therapy resistance as well as tumor recurrence has been demonstrated. In that respect, development of therapeutic strategies that target CSCs (and possibly also the tumor bulk) appears a promising approach in patients suffering from primary brain tumors. In the present study, we utilized RNA interference (RNAi) to screen the complete human kinome and phosphatome (682 and 180 targets, respectively) in order to identify genes and pathways relevant for the survival of brain CSCs and thereby potential therapeutical targets for glioblastoma. We report of 46 putative candidates including known survival-related kinases and phosphatases. Interestingly, a number of genes identified are involved in metabolism, especially glycolysis, such as PDK1 and PKM2 and, most prominently PFKFB4. In vitro studies confirmed an essential role of PFKFB4 in the maintenance of brain CSCs. Furthermore, high PFKFB4 expression was associated with shorter survival of primary glioblastoma patients. Our findings support the importance of the glycolytic pathway in the maintenance of malignant glioma cells and brain CSCs and imply tumor metabolism as a promising therapeutic target in glioblastoma. PMID- 22056880 TI - Predominant requirement of Bax for apoptosis in HCT116 cells is determined by Mcl 1's inhibitory effect on Bak. AB - The intrinsic mitochondrial apoptotic pathway acts through two core pro-apoptotic proteins Bax (Bcl2-associated X protein) and Bak (Bcl2-antagonist/killer 1). Although Bax and Bak seem to have redundant roles in apoptosis, accumulating evidence also suggests that they might not be interchangeable under certain conditions, at least in some human cell lines. Here we report the generation of Bak knockout as well as BaxBak double knockout HCT116 human colon carcinoma cells. We show that Bak is dispensable for apoptosis induced by a variety of stimuli including ABT-737 but not for fluorouracil-induced apoptosis. In addition, Bax deficiency only provides partial protection against camptothecin and cisplatin-induced apoptosis and no protection against killing by Puma or ABT 737 plus Noxa overexpression. Moreover, Bak is activated normally in response to many chemotherapeutic drugs in the presence of Bax, but remains kept in check by Mcl-1 in the absence of Bax. Our data suggest that Bax and Bak are functionally redundant, but they are counteracted by distinct anti-apoptotic Bcl-2 family proteins in different species. PMID- 22056881 TI - MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo. AB - MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375 mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG 1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3'-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase-PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2'-O-methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo, and highlight the therapeutic potential of miR-375 in HCC treatment. PMID- 22056882 TI - The quality of name-based species records in databases. PMID- 22056883 TI - Identification of human papillomavirus type 53 L1, E6 and E7 variants in isolates from Brazilian women. AB - Human papillomavirus type 53 (HPV 53), which belongs to genus Alpha, species A6, has spread among women worldwide. Although it is classified as a probably high risk type, the association between HPV 53 and the development of neoplastic cervical disease is unclear, and HPV 53 is known to be genomically diverse. We investigated 15 cases of HPV 53 genital infection in women living in the state of Rio de Janeiro that were not associated with severe intraepithelial cervical neoplasia. To trace HPV 53 variants in this geographic area, we characterized the L1, E6 and E7 genes from these isolates, and undertook a phylogenetic analysis based on multiple alignment of their L1 sequences. After amplification and sequence analysis, we identified seven different L1-E6-E7 variants and a L1 co infected isolate, which taken together had base pair changes at 29 different positions. The co-infected sample presented overlapped peaks at two positions. We also detected two new E6 genomic variants. Several base pair changes in the E6 region resulted in amino acid changes, three of which were non-conservative. The E7 gene was the most conserved sequence among those studied; in contrast, the E6 sequence reached a maximum difference of 2.79%. None of the HPV 53 isolates corresponded to the reference type. Dichotomical branching characteristic of HPV 53 was observed in all of the trees constructed, as well as in the concatenated phylogenetic tree. Probably, these variants pointing to evolutionary process, but they not appear to keep an increasing of pathogenesis Despite the limited number of samples analyzed in our work, we noticed that the same variant was found in more than one woman. Therefore, it is possible that such variants have been circulating in the female population in the state of Rio de Janeiro for a longer time or that due to host or genetic viral factors, these variants can spread more rapidly than others. PMID- 22056884 TI - Improved photocatalytic performance of ZnO nanograss decorated pore-array films by surface texture modification and silver nanoparticle deposition. AB - Immobilized photocatalyst was prepared by the growth of ZnO nanograss on the ZnO pore-array substrate. The surface morphology, optical and photocatalytic properties of the photocatalysts were studied. Nanograss decorated ZnO pore-array films exhibited improved performance on the photocatalytic degradation of methyl orange (MO) in aqueous solution under UV radiation. The photocatalytic activity of pore-array films can be tuned by changing the surface nanostructure of the porous photocatalyst. The enhanced photocatalytic activity of the nanostructured pore-array photocatalyst can be attributed to increased active surface area, improved diffusion of dye molecules among the nanostructured catalyst, and enhanced light absorption through the light-trapping effect. Besides, the degradation of MO using Ag/ZnO composite pore-array catalysts with different sizes and densities of the Ag particles on the surface of ZnO nanostructure was investigated. PMID- 22056885 TI - Efficient desulfurization by polymer-inorganic nanocomposite membranes fabricated in reverse microemulsion. AB - The sulfur in gasoline will convert to SO(2) after combustion under high temperature, which adversely affects human health and the environment. Membrane technique in particular pervaporation offers a number of potential advantages over conventional FCC gasoline desulfurization processes. The present study focuses on the performance enhancement of PDMS membrane by incorporating silica nanoparticles. Specifically, silica nanoparticles formed by the catalysis and templating of protamine in w/o reverse microemulsion are in situ embedded into PDMS bulk matrix, endowing the resultant oleophilic nanocomposite membranes with appropriate free volume properties and superior separation performance. Through the rational manipulation of biomimetic mineralization at water-oil interface, silica particles with uniform size are acquired. Following this protocol, by introducing organic PDMS oligomers into the oil phase, PDMS-SiO(2) nanocomposite membranes are prepared in a facile way. The resultant nanocomposite membranes display superior permeability and permselectivity in the pervaporative desulfurization using thiophene/n-octane binary mixture as model gasoline, for example, under the condition of 500 ppm sulfur in feed (40 L/h) at 30 degrees C, an enrichment factor of 4.83-5.82 with a normalized permeation rate of 6.61-10.76 * 10(-5)kgm/m(2)h is acquired. PMID- 22056886 TI - Sequestration of total and methyl mercury in different subcellular pools in marine caged fish. AB - Mercury contamination is an important issue in marine fish, and can cause toxicity to human by fish consumption. Many studies have measured the mercury concentrations in fish and estimated the threshold levels of its risk to human, but the mercury sequestration in different subcellular pools of fish is unclear. In this study, we investigated the concentration and distribution of total mercury (THg) and methylmercury (MeHg) in different subcellular fractions in the farmed red seabream, red drum, and black seabream from Fujian marine fish farms, China. We found that both THg and MeHg were dominantly bound with the cellular debris, followed by metallothionein-like protein>metal-rich granule>heat denatured protein>organelles pools. In general, Hg bound with the metal-sensitive fraction was small, indicating that Hg may have little toxicity to the fish (muscle). For the first time we showed that MTLP fraction had the highest % of total Hg as MeHg (88-91%) among all the subcellular fractions. Furthermore, the mercury concentration and subcellular distribution in the black seabream were both dependent on the fish size. Subcellular study may shed light on the detoxification of marine fish to Hg exposure and the potential bioavailability to humans due to fish consumption. PMID- 22056887 TI - Non-invasive in situ concentration determination of fluorescent or color tracers and pollutants in a glass pore network model. AB - This study presents a non-invasive imaging method for in situ concentration determination of conservative tracers and pollutants in a two-dimensional glass pore network model. The method presented is an extension to the work by Huang et al., and Thomas and Chysikopoulos. The method consists of fabricating the glass pore network model using a photolithography technique, conducting flowthrough contaminant transport experiments, taking digital photographs at various times of the two-dimensional pore network under ultraviolet or visible light source, and determining the spatially-distributed pollutant concentrations by measuring the color intensity in the photographs with comparative image analysis. Therefore, the method is limited to fluorescent or colored pollutants and tracers. The method was successfully employed to in situ concentration determination of uranine and red color tracers. PMID- 22056888 TI - Efficacy of EGFR tyrosine kinase inhibitors in patients with EGFR-mutated non small-cell lung cancer: a meta-analysis of 13 randomized trials. AB - Advanced non-small-cell lung cancer (NSCLC) harboring activating mutations of epidermal growth factor receptor (EGFR) are particularly sensitive to tyrosine kinase inhibitors (TKIs), namely erlotinib and gefitinib. The purpose of this meta-analysis was to evaluate the benefit of EGFR TKIs in EGFR-mutated NSCLCs. Eligible studies included published randomized controlled trials in which erlotinib or gefitinib (alone or with chemotherapy) were compared with standard therapy in 1260 patients with EGFR-mutated NSCLCs who were included in 13 trials. The mutational status was obtained through a retrospective or prospective analysis. Relative risk (RR) was calculated for response rate, and hazard ratios (HRs) were calculated for progression-free and overall survival. EGFR TKIs increase the chance of obtaining an objective response almost 2-fold when compared with chemotherapy (RR, 2.06; 2p < .00001). The response rate was 70% vs. 33.2% in first-line trials. In 3 second-line trials, response rates were 47.4% vs. 28.5%, with a benefit similar to first-line trials (RR, 1.79; 2p = .04). EGFR TKIs reduced the hazard of progression by 70% in all trials (HR, 0.30; 2p < .00001) and by 65% in first-line trials only (HR, 0.35; 2p < .00001). Overall, however, they do not improve survival (HR, 0.96; 2p = .71). NSCLCs harboring EGFR mutations derive greater benefit from erlotinib or gefitinib than from chemotherapy. All patients affected by NSCLC with an EGFR-positive mutation test result must be offered the opportunity to be treated with an EGFR TKI upfront or during the natural course of the disease if not previously exposed. PMID- 22056889 TI - Safety profile and tolerability of antiangiogenic agents in non-small-cell lung cancer. AB - Recent advances in understanding the importance of angiogenesis to tumor growth and distant metastasis has driven the development of antiangiogenic therapies for the treatment of non-small-cell lung cancer (NSCLC). The anti-vascular endothelial growth factor (VEGF) monoclonal antibody, bevacizumab, is the only US Food and Drug Administration-approved antiangiogenic agent for advanced NSCLC. Accumulated safety data with bevacizumab in NSCLC shows that patients are at risk for hemorrhage, venous thromboembolism, hypertension, and proteinuria. Investigational agents that target VEGF via a different mechanism (such as aflibercept [VEGF Trap]) or simultaneously inhibit multiple molecular pathways involved in angiogenesis (ie, multitargeted tyrosine kinase inhibitors [TKIs]) and vascular disrupting agents (VDAs) that target existing tumor vasculature are in various stages of clinical development for NSCLC, and safety profiles are emerging for these classes of agents. This review describes the molecular rationale for targeting angiogenic pathways in anticancer therapy and summarizes safety and tolerability data from clinical trials of bevacizumab or aflibercept in combination with chemotherapy and the investigational TKIs and VDAs in patients who have advanced NSCLC. PMID- 22056890 TI - Successful long-term treatment with pemetrexed of NSCLC associated with EML4-ALK and low thymidylate synthase expression. PMID- 22056891 TI - Perioperative socialization, care and monitoring of National Institutes of Health miniature swine undergoing ocular surgery and sampling of peripheral blood. AB - Swine are a frequent species of choice for testing new surgical procedures and for transplantation studies. However, information concerning best practice to prepare pigs for surgery and postoperative treatment and monitoring is limited, despite a perception that preoperative socialization is beneficial. Therefore we examined the effect of preoperative visits by project personnel on compliance of 26 National Institutes of Health (NIH) minipigs subject to corneal transplantation. We briefly describe sedation and anaesthesia protocols developed for surgery and multiple postoperative interventions in order to facilitate interpretation of data relating to pig compliance. Preoperative visit variables and measures of preoperative socialization were correlated with postoperative outcome. Principal component analysis (PCA) of postoperative outcome variables identified a factor accounting for 53.5% of the variance that was significantly associated with two factors derived from PCA of preoperative factors (accounting, respectively, for 54.7% and 26.0% of the variance; P = 0.019 for the overall model, P = 0.041 and 0.040 for factors 1 and 2, respectively), such that more time spent with pigs before surgery and higher socialization scores were associated with less postoperative stress and difficulty of eye medication. Moreover, two of the preoperative visit variables, time spent with only one person in the pen and time spent with two or more people in the pen, contributed predominantly to PCA factors 1 and 2, respectively, indicating that they were fulfilling two qualitatively different requirements for socialization. We conclude that NIH minipigs are fully compliant with anaesthetic and postoperative experimental procedures provided they are well-socialized to project personnel before surgery. PMID- 22056892 TI - Complications of injection laryngoplasty using calcium hydroxylapatite. AB - OBJECTIVE: To report the adverse effects of using calcium hydroxylapatite (CaHA) paste as a vocal fold filler. METHODS: Approval of this study was obtained through the institutional review board at Drexel University College of Medicine. Sixteen patients had 22 vocal fold injections with CaHA paste to treat glottic insufficiency. The initial procedures were performed at three different institutions between January 2006 and August 2009. Diagnosis and treatment of the complications in all cases were performed at our institution. Pre- and postinjection mucosal waves were assessed using strobovideolaryngoscopy when possible. All stroboscopic examinations were reviewed independently. Decreases in amplitude and waveform were classified as mild, moderate, or severe. Implant location was examined using computed tomography (CT) scan with 1-mm cuts through the larynx in patients suspected of having implant malposition. Vocal fold function was compared before and after injection, as well as after implant removal in selected cases. Histological section of explanted material was obtained. Major and minor complications were noted in 19 vocal folds. RESULTS: Ten major complications were encountered after surgery at three institutions. These included four vocal folds with adynamic mucosa, six with a severely decreased wave, and two granulomas affecting the vibratory margin. CT scanning confirmed six cases of implant malposition (possibly migration). Six implants were removed through endoscopic lateral cordotomy between 2 and 24 months after injection. Mucosal wave function recovered in five vocal folds after explantation. Minor complications were encountered in nine additional vocal folds. These included tissue inflammation marked by edema, erythema, and mild-to moderate mucosal wave restriction and hypervascularity. CONCLUSION: Injection laryngoplasty using CaHA paste has been regarded as an effective treatment for glottic insufficiency. In some patients, CaHA can cause an intense inflammatory reaction, potentially migrate, and compromise vocal fold function. It should be used with full understanding of the potential serious adverse reactions and risk of at least minor impairment of vibratory function. PMID- 22056893 TI - Measures of spectral slope using an excised larynx model. AB - Spectral measures of the glottal source were investigated using an excised canine larynx (CL) model for various aerodynamic and phonatory conditions. These measures included spectral harmonic difference H1-H2 and spectral slope that are highly correlated with voice quality but not reported in a systematic manner using an excised larynx model. It was hypothesized that the acoustic spectra of the glottal source were significantly influenced by the subglottal pressure, glottal adduction, and vocal fold elongation, as well as the resulting vibration pattern. CLs were prepared, mounted on the bench with and without false vocal folds, and made to oscillate with a flow of heated and humidified air. Major control parameters were subglottal pressure, adduction, and elongation. Electroglottograph, subglottal pressure, flow rate, and audio signals were analyzed using custom software. Results suggest that an increase in subglottal pressure and glottal adduction may change the energy balance between harmonics by increasing the spectral energy of the first few harmonics in an unpredictable manner. It is suggested that changes in the dynamics of vocal fold motion may be responsible for different spectral patterns. The finding that the spectral harmonics do not conform to previous findings was demonstrated through various cases. Results of this study may shed light on phonatory spectral control when the larynx is part of a complete vocal tract system. PMID- 22056894 TI - Normal neurodynamic responses of the femoral slump test. AB - Femoral slump test is a neurodynamic testing, which could be used to assess the mechanosensitivity of the femoral component of the nervous system. Although Trainor and Pinnington reported the diagnosis accuracy of the femoral slump test, the neurodynamic responses of the femoral slump test have never been studied. The purposes of this study were to evaluate whether maneuvers that changed the nerve tension altered the responses of the femoral slump test and if these responses were influenced by gender and leg dominance; and to identify the correlations between flexibility and measured hip extension angle. Thirty-two asymptomatic subjects (16 males, 16 females) were recruited. The femoral slump test was performed in trunk slump and neutral positions, and cervical extension was used as the structure differential technique. Hip extension angle and visual analog scale (VAS) of thigh pain was measured during the test. Our results showed the decrease of nerve tension significantly increased hip extension ROM (P < 0.001) and lowered pain intensity (P < 0.001). The hip extension ROM was similar between genders but smaller for the dominant leg, as compared to the non-dominant side (P < 0.05); and the hip ROM did not correlate with any of the flexibility indices (P > 0.05). These findings indicated that femoral slump test resulted in normal neurodynamic responses in individuals free of lower extremity problems, and these responses were independent of the influence of muscle flexibility or gender. Future research should emphasize the use of femoral slump test in patient groups such as low back and anterior knee pain. PMID- 22056895 TI - Principles of psychosomatic assessment. AB - There is increasing awareness of the limitations of disease as the primary focus of medical care. It is not that certain disorders lack an organic explanation, but that our assessment is inadequate in most clinical encounters. The primary goal of psychosomatic medicine is to correct this inadequacy by incorporation of its operational strategies into clinical practice. At present, the research evidence which has accumulated in psychosomatic medicine offers unprecedented opportunities for the identification and treatment of medical problems. Taking full advantage of clinimetric methods (such as with the use of Emmelkamp's two levels of functional analysis and the Diagnostic Criteria for Psychosomatic Research) may greatly improve the clinical process, including shared-decision making and self-management. Endorsement of the psychosomatic perspective may better clarify the pathophysiological links and mechanisms underlying symptom presentation. Pointing to individually targeted methods may improve final outcomes and quality of life. PMID- 22056896 TI - The psychosomatic interview. AB - The psychosomatic interview is a patient-focused dialogue between physician and patient. It differs from the traditional disease-focused encounter in that the psychosomatic approach includes the biological, psychological, and sociocultural domains irrespective of the patients initial complaint, whether somatic or psychological. The process of dyadic interaction and the techniques of open questions are reviewed. Specific issues such as the alexithymic patient and breaking bad news are challenges in such communications. Organizing the data into the perspectives of diseases, dimensions, behaviors, and life stories allows the clinician to best understand their patients within a psychosomatic milieu. PMID- 22056897 TI - Evaluating childhood adversity. AB - Childhood adversity increases risk of psychological and physical disorders. The comprehensive psychosomatic assessment of an individual's vulnerability to illness includes the evaluation of early life events, especially exposure to physical, emotional, sexual abuse and neglect. Many self-report and observer rated instruments are now available to aid this evaluation and increase its validity. The authors review the features and limitations of published tools, and recommend which to choose for clinical and research purposes. PMID- 22056898 TI - Evaluating life events and chronic stressors in relation to health: stressors and health in clinical work. AB - Despite the fact that there is an extensive scientific literature regarding the importance of exposure to psychosocial stressors, the assessment of such stressors is often neglected in clinical work. The present review summarizes the scientific literature on critical life changes and work-related stressors. Particular emphasis has been on somatic outcomes and physiological processes that have been shown to be affected by exposure to stressors. Although the relationships are highly complex, it could be concluded that exposure to stressors may often determine the onset of many illnesses. Standardized well functioning assessment instruments that could be used in clinical practice exist and should be used. PMID- 22056899 TI - Assessment of lifestyle in relation to health. AB - Habits relevant to health include physical activities, diet, smoking, drinking and drug consumption. Despite the fact that benefits of modifying lifestyle are increasingly demonstrated in clinical and general populations, assessment of lifestyle and therapeutic lifestyle changes is neglected in practice. In this review, associations between unhealthy lifestyle and health outcomes are presented. Particular emphasis will be placed on description and discussion of the standardized assessment instruments and behavioral methods that could be used in clinical practice to measure lifestyles. PMID- 22056900 TI - Assessment of sexual function in the medically ill: psychosomatic approach to sexual functioning. AB - Good sexual functioning is a part of overall well-being. Assessment of sexual functioning should be part of any complete psychosomatic assessment. The cornerstone of this assessment is a comprehensive clinical interview of the patient, with, if possible, collateral information obtained from the partner or another clinician. In addition, comprehensive assessment of sexual function should include a physical examination with a special focus on sexual function, laboratory testing and possibly other specialized testing and, in some cases, psychometric assessment. The results of a thorough assessment may serve as a basis for considering possible etiology(ies) of sexual dysfunction, coexisting comorbidities and as a starting point of managing sexual dysfunction. PMID- 22056901 TI - Psychological factors in medical disorders assessed with the diagnostic criteria for psychosomatic research. AB - The Diagnostic Criteria for Psychosomatic Research (DCPR) are a diagnostic and conceptual framework that aims to translate psychosocial variables that derived from psychosomatic research into operational tools whereby individual patients could be identified. A set of 12 syndromes was developed and grouped in the clusters of abnormal illness behavior (health anxiety, disease phobia, thanatophobia, and illness denial), somatization (functional somatic symptoms secondary to a psychiatric disorder, persistent somatization, conversion symptoms, and anniversary reaction), irritability (type A behavior, irritable mood), demoralization, and alexithymia. This chapter aims to illustrate the criteria for each of the 12 DCPR syndromes and how to diagnose them with the aid of the DCPR Structured Interview, as illustrated in a clinical example. PMID- 22056902 TI - Mood and anxiety in the medically ill. AB - In this review on rating scales for anxiety and depression, only instruments considered to be quantifiable, analogue to the measurement of hypertension in the medical setting, have been selected. The clinimetric method for validating these rating scales is the item response theory model in which the individual items are rank ordered on the dimensions of anxiety or depression, resulting in their total score being a sufficient statistic. The measurement of anxiety and mood on their respective dimensions of severity implies that we can speak of primary and secondary anxiety or depression in the same way as we speak about primary hypertension (without a medical explanation) and secondary hypertension (when caused be various medical conditions). Both clinician-rated scales and patient rated questionnaires are discussed. The Clinical Interview for Depression and Related Syndromes (CIDRS) is included in the appendix as this CIDRS covers many of the rating scales measuring mood and anxiety. PMID- 22056903 TI - Assessment of personality in psychosomatic medicine: current concepts. AB - The notion that personality variables can affect vulnerability to specific diseases has been widely promoted in psychosomatic medicine. Over the time, some personality patterns have been extensively studied. Among them, alexithymia, type A, and type D personality are the most relevant. However, also temperament and character has increasingly been object of studies. Alexithymia is currently recognized as a risk factor for medical, psychiatric, or behavioral problems; type A personality is recognized to increase the risk for coronary artery disease, and type D personality has been related to adverse cardiac events and cardiovascular outcomes. The growing interest and clinical role of the personality constructs in psychosomatic medicine has been favored by the revolutionary understanding that personality factors are not causes of medical disease but their moderators/mediators, and by the decline of the psychometric distinction between state and trait. Indeed, it is nowadays recognized that psychological constructs traditionally conceived as trait dimensions may surprisingly display sensitivity to change in specific clinical situations. Assessing personality, thus, has become worth pursuing since it may give unique information about individuals with medical conditions and contribute to completely understand medical patients and their global health as well as formulating optimal decision-making and treatment planning. In this framework, the present chapter has the aim to provide insight into personality dimensions in psychosomatic medicine and describe the main instruments to assess it. PMID- 22056904 TI - Illness behavior. AB - The term illness behavior was introduced by Mechanic and Volkart to describe the individuals' different ways to respond to their own health status. Pilowsky's concept of abnormal illness behavior encompasses several clinical conditions characterized by a maladaptive mode of experiencing, perceiving, evaluating and responding to one's own health status. The concept of somatization was criticized because it implies the presence of psychological distress or an underlying psychiatric disturbance when an organic cause for somatic symptoms is not found. Thus, more atheoretical terms , such as functional somatic symptoms and medically unexplained symptoms, were introduced. Both Kellner's Symptom Questionnaire and Derogatis' Symptom Checklist-90 include a scale for somatic symptoms, and other questionnaires were specifically designed to measure their frequency and severity. Kellner's Illness Attitude Scales appear to be the gold standard for the measurement of the hypochondriacal spectrum, which includes several clinical conditions, such as nosophobia, thanatophobia and health anxiety. The assessment of illness denial should consider that a certain degree of denial may sometimes prevent patients from overwhelming psychological distress resulting from life threatening or stigmatized diseases. Denial may concern both physical and psychiatric symptoms. Specific instruments are available for both types of denial. The cognitive and emotional representations developed by subjects when they have to cope with an illness or a perceived health threat are subsumed under the concept of illness perception and may be assessed by the Brief Illness Perception Questionnaire. PMID- 22056905 TI - Assessment of psychological well-being in psychosomatic medicine. AB - The measures of disease status alone are insufficient to describe the burden of illness or one's attitudes toward illness and life. The subjective health status including psychological resources and well-being is as valid as that of the clinician when it comes to evaluating outcomes. The aim of this chapter is to provide a theoretical framework for the assessment of psychological well-being and positive functioning and to review the literature supporting the influence of these positive dimensions on illness development and health protection. We selected the assessment tools such as Kellner's Symptom Questionnaire, Antonovsky's Sense of Coherence, Ryff's Psychological Well-Being Scales and Psychosocial Index that we found most helpful in clinical and psychosomatic practice and that displayed clinimetric properties of sensitivity in research. PMID- 22056906 TI - Family assessment in the medical setting. AB - Acute and chronic illness exists in a social context. A biopsychosocial assessment should include an evaluation of the patient's social situation, the nature of the patient's interpersonal connections, and his/her family's functioning. Families can influence health by direct biological pathways, health behavior pathways, and psychophysiological pathways. There are a large number of family-based risks factors as well as many protective relational factors that influence the onset and course of illness. A family assessment is the first step in determining both the need for further intervention and the specific areas of family life that might need to be addressed. A family assessment provides information about the social substrate for the evolution of the presenting complaint as well as information to better understand the patient's problems. There are many ways to assess families, and there are a variety of family assessment instruments to help with the assessments. Clinician will be best served by becoming familiar and comfortable with at least one assessment model that is consistent, structured, and evaluates a wide range of family functions. Such an assessment can be incorporated into routine clinical care. A good family assessment can be therapeutic in and of itself even if the decision is made that no further family intervention is indicated. PMID- 22056907 TI - Relational ethics and psychosomatic assessment. AB - The main ethical perspective in the clinical relationship takes into consideration the vulnerability of the clinical condition before threats and risks that can undermine the integrity and dignity of the person. Psychosomatic medicine faces complex cases whose ethical problems cannot only be solved by applying top-down deontological or utilitarian approaches, principlism, which is limited mainly to easing ethical tensions, or a bottom-up approach, the casuistic model, case-based reasoning. In introducing vulnerability as the core of ethical questioning as a principle ontological priority over other principles, relational ethics refers to the appreciation of the responsibility of health professionals through which a health care professional and the patient 'together' can construct more reasonable and prudential courses of action with, for, and by the patient. The model of relational ethics is based on three main aspects, clinically integrated approach, science/philosophy partnership, and deliberative process, that when taken together, form an intermediate model that ensures prudent and reasonable decision-making. The three structural elements and characteristics of relational ethics create and maintain a responsible relationship between the professional and the patient being aware that the mutual vulnerability of health professional and the patient has a moral value and recognizing that their relationship will allow for personal development of each. I conceptualized the model of relational ethics as one that embraces the meta-ethical principles of vulnerability, dignity, responsibility, and respect for autonomy as they are considered by many international declarations or conventions. This model integrates three key polarities: ensure conditions of authenticity, facilitate a process of cooperative mutuality, and promote opportunities for growth and development. Relational ethics can be used to solve major ethical problems in psychosomatic medicine, capacity , informed consent, and confidentiality. PMID- 22056909 TI - First evidence of an intimate symbiotic association between fungi and larvae in basal attine ants. AB - The most conspicuous ants in all of tropical America are those that belong to the tribe Attini which cultivate fungus. The objective of the present study is to verify the alterations that occur in the cuticle of the worker larvae from Myrmicocrypta, Mycetarotes and Trachymyrmex with the purpose of trying to establish the degree of this association. Attine ants from the Atta genus were used as a control group. The analysis of histological sections showed results about the distribution of the cells and tissues on the epidermis of A. sexdens rubropilosa ant larvae and Mycetarotes parallelus, Trachymyrmex fuscus and Myrmicocrypta sp. A cuticle covering the ants was observed in the larvae of all the species, and this is formed by a simple cubic epithelium, whose cells possibly change its shape to prismatic, depending on their secretory activity. Just under this epithelium large adipose cells with reserve granules in their cytoplasm were found. The presence of a space filled by granulose and acellular material was also observed, indicating that the larvae were in a molt period. The presence of fungal hyphae is observed both on the external side of the basal attine larvae as well as emitting projections to the interior of the cuticle reaching the epithelium and the adipocyte cells. Data obtained in the present study demonstrated that the fungus deposited on the surface of immature ants from attine basal species maintain a close relationship with them, once the fungus hyphae have the ability to disorganize the cuticle lamellas, penetrating the interior of the insect cells through the emission of prolongations transporting the cuticle and epithelium barriers and making substances exchanges between larvae and fungus. PMID- 22056908 TI - Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models? AB - The development of metabolic dysfunctions like diabetes and insulin resistance in mammals is regulated by a myriad of factors. Oxidative stress seems to play a central role in this process as recent evidence shows a general increase in oxidative damage and a decrease in oxidative defense associated with several metabolic diseases. These changes in oxidative stress can be directly correlated with increased fat accumulation, obesity, and consumption of high-calorie/high fat diets. Modulation of oxidant protection through either genetic mutation or treatment with antioxidants can significantly alter oxidative stress resistance and accumulation of oxidative damage in laboratory rodents. Antioxidant mutant mice have previously been utilized to examine the role of oxidative stress in other disease models, but have been relatively unexplored as models to study the regulation of glucose metabolism. In this review, we will discuss the evidence for oxidative stress as a primary mechanism linking obesity and metabolic disorders and whether alteration of antioxidant status in laboratory rodents can significantly alter the development of insulin resistance or diabetes. PMID- 22056911 TI - KIF20A mRNA and its product MKlp2 are increased during hepatocyte proliferation and hepatocarcinogenesis. AB - Mitotic kinesin-like protein 2 (MKlp2), a microtubule-associated motor, is required during mitosis exit for the final step of cytokinesis. It also contributes to retrograde vesicular trafficking from the Golgi apparatus to the endoplasmic reticulum in interphase. The KIF20A gene encoding MKlp2 is controlled by the E2F-retinoblastoma protein-p16 pathway, and its widely expressed mRNA is found in fetal and proliferating adult tissues. The expression pattern and function of MKlp2 in the adult liver, however, have not been investigated. We report herein that MKlp2 transiently accumulates in vivo during mouse liver regeneration after partial hepatectomy and is strongly overexpressed in preneoplastic and neoplastic mouse liver. In vitro in mitogen-stimulated primary hepatocytes, MKlp2 accumulated in the nucleus during the G2 phase of the cell cycle coincident with the mitotic kinase Aurora B. Human hepatoma cell lines exhibited high levels of MKlp2; however, it was undetectable in normal human hepatocytes. RNAi-mediated MKlp2 knockdown in hepatoma cells induced polyploidization consistent with its essential function in promoting cytokinesis and inhibited cell proliferation without inducing apoptosis. KIF20A mRNA was strongly accumulated in a large series of human hepatocellular carcinomas, with the highest expression observed in tumors with genomic instability. Accumulation of MKlp2 in normal proliferating, preneoplastic, and transformed hepatocytes suggests that MKlp2 contributes to both normal and pathologic hepatocyte proliferation and is linked to tumor aggressiveness in human hepatocellular carcinomas. PMID- 22056910 TI - Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms. AB - The hedgehog (HH) signaling pathway is a highly regulated signaling pathway that is important not only for embryonic development, tissue patterning, and organogenesis but also for tissue repair and the maintenance of stem cells in adult tissues. In the adult hematopoietic system, HH signaling regulates intrathymic T-cell development, and it is one of the survival signals provided by follicular dendritic cells to prevent apoptosis in germinal center B cells. HH signaling is required for primitive hematopoiesis; however, conflicting data have been reported regarding the role of the HH pathway in adult hematopoiesis. Inappropriate activation of the HH signaling pathway occurs in several human cancers, including hematological neoplasms. Emerging data demonstrate abnormal HH pathway activation in chronic lymphocytic leukemia/small lymphocytic lymphoma, plasma cell myeloma, mantle cell lymphoma, diffuse large B-cell lymphoma, ALK positive anaplastic large cell lymphoma, chronic myelogenous leukemia, and acute leukemias. In these neoplasms, HH signaling promotes proliferation and survival, contributes to the maintenance of cancer stem cells, and enhances tolerance or resistance to chemotherapeutic agents. Here, we review current understanding of HH signaling, its role in the pathobiology of hematological malignancies, and its potential as a therapeutic target to treat malignant hematological neoplasms. PMID- 22056912 TI - A novel melano-lysosome in the retinal epithelium of rhesus monkeys. AB - The large phagocytic load that confronts the retinal pigment epithelium (RPE) is thought to play a possible role in the pathogenesis of age related macular degeneration (AMD) that afflicts both humans and monkeys. Our knowledge of how RPE degrades phagosomes and other intra-cellular material by lysosomal action is still rudimentary. In this paper we examine organelles that play a role in this process, melanosome, lysosomes and phagosomes, in the RPE of young and old rhesus monkeys in order to better understand lysosomal autophagy and heterophagy in the RPE and its possible role in AMD. We used electron microscopy to detect and describe the characteristics of melanosomes and lysosome-like organelles in the macular RPE of rhesus monkeys (Macaca mulatta) that were 1, 6, 24, 24, 26 and 35 years of age. The measurements include the number, shape and size of these organelles located in the basal, middle and apical regions of RPE cells. Phaagosomes were also examined but not counted or measured for size or shape because of their rarity. Melanosomes were homogeneously dark with a circular or elliptical shape and decreased in number with age. Smaller melanosomes were more common at the basal side of the RPE. Among the small melanosomes, we found an organelle that was losing melanin in varying degrees; in some cases was nearly devoid of melanin. Because of the melanin loss, we considered this organelle to be a unique type of autophagic melano-lysosome, which we called a Type 1 lysosome. We found another organelle, more canonically lysosomal, which we called a Type 2 lysosome. This organelle was composed of a light matrix containing melanosomes in various stages of degradation. Type 2 lysosomes without melanosomes were rare. Type 2 lysosomes increased while Type 1 decreased in number with age. Phagosomes were rare in both young and old monkeys. They made close contact with Type 2 lysosomes which we considered responsible for their degradation. Melanosomes are being lost from monkey RPE with age. Much of this loss is carried out by two types of lysosomes. One, not defined as unique before, appears to be autophagic in digesting its own melanin; it has been called a Type 1 lysosome. The other, a more canonical lysosome, is both heterophagic in digesting phagosomes and autophagic in digesting local melanosomes; it has been called a Type 2 lysosome. Type 1 lysosomes decrease while type 2 lysosomes increase with age. The loss of melanin is considered to be detrimental to the RPE since it reduces melanin's protective action against light toxicity and oxidative stress. Phagosomes appear to be degraded by membrane contacts with Type 2 lysosomes. The loss of melanin and the buildup of Type 2 lysosomes occur at an earlier age in monkeys than humans implying that a greater vulnerability to senescence accelerates the rate of AMD in monkeys. PMID- 22056913 TI - A three-dimensional finite element model and image reconstruction algorithm for time-domain fluorescence imaging in highly scattering media. AB - In this work, development and evaluation of a three-dimensional (3D) finite element model (FEM) based on the diffusion approximation of time-domain (TD) near infrared fluorescence light transport in biological tissue is presented. This model allows both excitation and fluorescence temporal point-spread function (TPSF) data to be generated for heterogeneous scattering and absorbing media of arbitrary geometry. The TD FEM is evaluated via comparisons with analytical and Monte Carlo (MC) calculations and is shown to provide a quantitative accuracy which has less than 0.72% error in intensity and less than 37 ps error for mean time. The use of the Born-Ratio normalized data is demonstrated to reduce data mismatch between MC and FEM to less than 0.22% for intensity and less than 22 ps in mean time. An image reconstruction framework, based on a 3D FEM formulation, is outlined and simulation results based on a heterogeneous mouse model with a source of fluorescence in the pancreas is presented. It is shown that using early photons (i.e. the photons detected within the first 200 ps of the TPSF) improves the spatial resolution compared to using continuous-wave signals. It is also demonstrated, as expected, that the utilization of two time gates (early and latest photons) can improve the accuracy both in terms of spatial resolution and recovered contrast. PMID- 22056914 TI - Detection of Mimivirus in bronchoalveolar lavage of ventilated and nonventilated patients. AB - BACKGROUND/AIMS: We investigated the prevalence of Mimivirus in bronchoalveolar lavage (BAL) specimens from ventilated versus nonventilated patients. METHODS: The occurrence of Mimivirus DNA was evaluated by two previously developed real time PCR assays in 69 BAL specimens: 30 from patients on mechanical ventilation for at least 48 h and 39 from nonventilated patients from different clinical settings, including lung transplant recipients. RESULTS: None of the BAL specimens from ventilated and nonventilated patients resulted positive for Mimivirus. CONCLUSION: This study, similarly to other studies that used molecular assays to detect Mimivirus, found no occurrence of the virus in the lower respiratory tract, thus being in contrast to serological investigations which reported a significant association between Mimivirus and the development of pneumonia. Gene polymorphism could explain these results or, alternatively, it could be hypothesized that Mimivirus does not represent a common cause of lower respiratory tract infection in either ventilated or nonventilated patients. Further studies on a larger population of patients from a different clinical setting evaluating both serology and DNA detection in lower respiratory tract specimens, including BAL and possibly tissue samples, could allow a better definition of the epidemiological and pathological role of Mimivirus in the development of pneumonia. PMID- 22056915 TI - Calcium phosphate nanoparticles with an asymmetric lipid bilayer coating for siRNA delivery to the tumor. AB - Calcium phosphate (CaP) nanoparticles (NP) with an asymmetric lipid bilayer coating have been designed for targeted delivery of siRNA to the tumor. An anionic lipid, dioleoylphosphatydic acid (DOPA), was employed as the inner leaflet lipid to coat the nano-size CaP cores, which entrap the siRNA, such that the coated cores were soluble in organic solvent. A suitable neutral or cationic lipid was used as the outer leaflet lipid to form an asymmetric lipid bilayer structure verified by the measurement of NP zeta potential. The resulting NP was named LCP-II with a size of about 25 to 30nm in diameter and contained a hollow core as revealed by TEM imaging. PEGylation of NP was done by including a PEG phospholipid conjugate, with or without a targeting ligand anisamide, in the outer leaflet lipid mixture. The sub-cellular distribution studied in the sigma receptor positive human H460 lung cancer cells indicated that LCP-II could release more cargo to the cytoplasm than our previous lipid/protamine/DNA (LPD) formulation, leading to a significant (~40 fold in vitro and ~4 fold in vivo) improvement in siRNA delivery. Bio-distribution study showed that LCP-II required more PEGylation for MPS evasion than the previous LPD, probably due to increased surface curvature in LCP-II. PMID- 22056917 TI - Physical properties and valence state of cerium in the filled skutterudite CePt4Ge12. AB - Electronic, magnetic, and transport properties of the filled platinum-germanium skutterudite CePt4Ge12 are investigated. High resolution x-ray absorption spectroscopy measurements at the cerium L(III) edge demonstrate that CePt4Ge12 in this compound has a temperature-independent valence close to three. However, magnetic susceptibility, thermopower, Hall effect, and electronic specific heat reveal a broad maximum at Tmax D 65-80 K, suggesting the presence of valence fluctuations. The Sommerfeld coefficient gamma = 105 mJ mol-1 K-2, deduced from specific heat, indicates moderately enhanced band masses for CePt4Ge12. We discuss these findings and conclude that CePt4Ge12 represents a system at the border between intermediate valence (IV) and Kondo lattice behavior. In addition, the lattice specific heat and the thermal conductivity are discussed with respect to the vibrational dynamics of Ce in the [Pt4Ge12] framework. PMID- 22056916 TI - Peptides in cancer nanomedicine: drug carriers, targeting ligands and protease substrates. AB - Peptides are attracting increasing attention as therapeutic agents, as the technologies for peptide development and manufacture continue to mature. Concurrently, with booming research in nanotechnology for biomedical applications, peptides have been studied as an important class of components in nanomedicine, and they have been used either alone or in combination with nanomaterials of every reported composition. Peptides possess many advantages, such as smallness, ease of synthesis and modification, and good biocompatibility. Their functions in cancer nanomedicine, discussed in this review, include serving as drug carriers, as targeting ligands, and as protease-responsive substrates for drug delivery. PMID- 22056918 TI - Alterations of serotonin 2C and 2A receptors in response to T10 spinal cord transection in rats. AB - Recent studies reported that a recovery of motoneurons after spinal cord transection at the sacrocaudal level may depend on adaptive alterations of the serotonin 2C (5-HT(2C)R) and 2A (5-HT(2C)R) receptor function via changes in mRNA editing or protein expression, respectively. It has been suggested that depletion of serotonergic input may drive these adaptations. Here, mRNA editing and/or expression of 5-HT(2C)R and 5-HT(2A)R was evaluated in rats that sustained a complete transection at the thoracic (T10) level. While 5-HT(2A)R mRNA expression was upregulated below the site of spinal cord injury (SCI), no changes in 5 HT(2C)R mRNA editing or expression were detected. These findings argue against the hypothesis that 5-HT(2C)R editing is regulated by extracellular serotonin levels. Rather, it appears that the editing process is just one of the ways in which excitability of motor neurons can be restored following SCI. To this end, the influence of excitatory locomotor circuits on motor neurons in the thoracic spinal cord of rats requires further exploration. PMID- 22056919 TI - Neocortical Posttraumatic Epileptogenesis. AB - Development of new excitatory connectivity and decreases in GABAergic inhibition are mechanisms underlying posttraumatic epileptogenesis in animal models. Experimental strategies that interfere with these processes, applied between the trauma andseizure onset, are antiepileptogenic in the laboratory, and have promise for prophylaxis of epileptogenesis after cortical injury in man. For an expanded treatment of this topic see Jasper's Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press. Available on NCBI Bookshelf. PMID- 22056920 TI - Definitions and outcome measures for bullous pemphigoid: recommendations by an international panel of experts. AB - Our scientific knowledge of bullous pemphigoid (BP) has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in BP. A major obstacle in sharing multicenter-based evidences for therapeutic efforts is the lack of generally accepted definitions for the clinical evaluation of patients with BP. Common terms and end points of BP are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. These recommendations from the International Pemphigoid Committee represent 2 years of collaborative efforts to attain mutually acceptable common definitions for BP and proposes a disease extent score, the BP Disease Area Index. These items should assist in the development of consistent reporting of outcomes in future BP reports and studies. PMID- 22056921 TI - Deposition of beryllium-7 in Hsinchu, Taiwan. AB - In the present study, factors that influence the distribution and variation of (7)Be in Hsinchu, Taiwan were elucidated. The (7)Be activity including the deposition flux and air concentration was continuously monitored and recorded throughout a 15-year period (1996-2010). To explain the observed variability in the (7)Be activity over time, air concentration and deposition flux of (7)Be were correlated to rainfall and solar activity. The monthly average deposition flux and air concentration of (7)Be were inversely related to solar activity with the 11-year cycle and were not strongly correlated to rainfall. The highest seasonal deposition flux of (7)Be occurred in March, which is commonly referred to as the spring maximum, due to air-mass mixing processes in the troposphere. The air concentration of (7)Be was seasonally variable and was significantly affected by monsoons. The lowest deposition flux and air concentration of (7)Be were observed in July and August due to the occurrence of southwest monsoons from low latitudes, which carry air masses with low concentrations of (7)Be. The deposition flux was enhanced by precipitation, which increased the deposition velocity, transferring more (7)Be from the troposphere to the ground. The fraction of dry to total deposition varied seasonally and was equal to 9.86%, on average. PMID- 22056922 TI - Recent health care transitions and emergency department use by chronic long term care residents: a population-based cohort study. AB - OBJECTIVES: Long term care (LTC) residents commonly experience transitions between health care settings that can have important health consequences. The objective of this study was to quantify the effect of recent transitions on the risk of emergency department (ED) transfer among chronic LTC residents. Two types of transitions were considered: admission into LTC and discharge from hospital. DESIGN: Retrospective cohort study using linked administrative data from Ontario, Canada. PARTICIPANTS: All chronic LTC residents in Ontario older than 66 years on the date of the 2005 provincial LTC facility census. MEASUREMENTS: Using facility census date as baseline, admission to LTC was defined as the number of days between LTC admission and baseline. Residents were categorized as one of: newly admitted (<=30 days), shorter-stay (31-90 days), or longer-stay (>=91 days). Within each group, residents were further subdivided based on having had a recent discharge from hospital. The first ED visit for each resident during the 6-month follow-up was counted, as were death and other competing risks. The cumulative incidence of ED transfer for each group was estimated and logistic regression was used to test whether differences between groups persisted after controlling for resident characteristics. RESULTS: Of the 64,589 residents, 3.0% were newly admitted, 4.9% were shorter-stay, and 92.1% were longer-stay. The 6-month cumulative incidences of ED transfers were 35.0% for newly admitted, 30.7% for shorter-stay, and 22.0% for longer-stay. The odds of an ED transfer were higher for newly admitted and shorter-stay residents relative to longer-stay residents, even after adjustment for resident characteristics (adjusted odds ratio, 95% confidence interval 1.9, 1.7-2.1; and 1.5, 1.4-1.7, respectively). Regardless of time since LTC admission, residents with a recent discharge from hospital had a cumulative incidence of nearly 40% and an increase in the odds of ED transfer of at least 50% compared with those who had not been in hospital. CONCLUSIONS: Health care transitions, especially those from hospital, are associated with an increase in ED transfers among older chronic LTC residents. These findings highlight the need for a stronger focus on transitional care, especially posthospital care, for LTC residents. PMID- 22056923 TI - A novel model of cardiovascular risk based on kidney function. AB - BACKGROUND/AIMS: Although creatinine-based estimated glomerular filtration rate (eGFR) is associated with cardiovascular events, threshold values for optimum discrimination are unclear. We aimed to identify serum creatinine and eGFR thresholds of maximum sensitivity and specificity (Max(Sn+Sp)) for a composite outcome of coronary heart disease, stroke, and death. METHODS: Classification tree methodology defined the hierarchical rank of serum creatinine, eGFR, and cardiovascular risk factors in adults aged 45-64 years (Atherosclerosis Risk in Communities Study, n = 15,582; follow-up, 13.1 years). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study, and Cockcroft-Gault corrected for body surface area (CG/BSA) eGFR equations were used. RESULTS: The mean study population age was 54.2 years; 26.4% were African-American. The mean standardized creatinine level was 0.83 mg/dl. The mean eGFR(CKD-EPI), eGFR(MDRD), and eGFR(CG/BSA) values were 95.7, 98.6, and 99.7 ml/min/1.73 m(2), respectively. The composite outcome occurred for 22.1% of the population. For all eGFR measures, sensitivity was <0.05 and specificity >0.98 for thresholds of 60 ml/min/1.73 m(2). Max(Sn+Sp) for serum creatinine occurred at 0.73 mg/dl (sensitivity 0.66/specificity 0.48); corresponding values for eGFR(CKD-EPI), eGFR(CG/BSA), and eGFR(MDRD) were 95 (0.52/0.59), 90 (0.44/0.67), and 75 (0.16/0.91) ml/min/1.73 m(2), respectively. Considering optimum thresholds for 10 modifiable risk factors, high-density lipoprotein cholesterol <=44 mg/dl ranked first; rankings for optimum renal function thresholds varied between sixth and tenth. CONCLUSIONS: Optimum eGFR thresholds for community-based risk triage were substantially higher than 60 ml/min/1.73 m(2), which currently defines moderate abnormality. Utility of creatinine-based risk triage in older adults appears modest. PMID- 22056925 TI - Giant pulmonary and hepatic hydatid cysts in a child. AB - This case report focuses on hydatidosis, one of the most important parasitic zoonoses in Romania. We describe an interesting paediatric case of an eight-year old boy from a rural region presenting with a both giant and life-threatening pulmonary cyst (that was successfully managed) and a hepatic cyst. Noteworthy are the negative consequences of this disorder on children's health and development as a result of prolonged hospitalizations, surgical interventions and chemotherapy. PMID- 22056924 TI - Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors. AB - Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for 6 weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, -14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats. PMID- 22056926 TI - FtsZ-ZapA-ZapB interactome of Escherichia coli. AB - Bacterial cell division relies on the formation and contraction of the Z ring, coordinated and regulated by a dynamic protein complex called the divisome. The cell division factor ZapA interacts directly with FtsZ and thereby increases FtsZ protofilament association and Z-ring stability. Here, we investigated ZapB interaction with ZapA and its effect on Z-ring formation and FtsZ protofilament bundling. The combination of the ftsZ84 allele that encodes an FtsZ variant that polymerizes inefficiently with a zapB null mutant resulted in a synthetic defective phenotype. Overproduction of ZapA led to the formation of aberrant FtsZ helical structures and delocalization of ZapB. The N-terminal end of ZapB was essential for ZapB-ZapA interaction, and amino acid changes close to the N terminus of ZapB exhibited reduced interaction with ZapA. Sedimentation assays showed that ZapB interacts strongly with ZapA and reduces ZapA's interaction with FtsZ in vitro. The morphology of the structures formed by ZapA and ZapB together was similar to the cables formed by ZapB in the presence of CaCl(2), a known ZapB bundling agent. The in vivo and in vitro data support a model in which ZapA interacts strongly with ZapB and the ZapA-ZapB interaction is favored over ZapA FtsZ. PMID- 22056927 TI - Effects on growth by changes of the balance between GreA, GreB, and DksA suggest mutual competition and functional redundancy in Escherichia coli. AB - It is well known that ppGpp and DksA interact with bacterial RNA polymerase (RNAP) to alter promoter activity. This study suggests that GreA plays a major role and GreB plays a minor role in the ppGpp-DksA regulatory network. We present evidence that DksA and GreA/GreB are redundant and/or share similar functions: (i) on minimal medium GreA overproduction suppresses the growth defects of a dksA mutant; (ii) GreA and DksA overexpression partially suppresses the auxotrophy of a ppGpp-deficient strain; (iii) microarrays show that many genes are regulated similarly by GreA and DksA. We also find instances where GreA and DksA seem to act in opposition: (i) complete suppression of auxotrophy occurs by overexpression of GreA or DksA only in the absence of the other protein; (ii) PgadA and PgadE promoter fusions, along with many other genes, are dramatically affected in vivo by GreA overproduction only when DksA is absent; (iii) GreA and DksA show opposite regulation of a subset of genes. Mutations in key acidic residues of GreA and DksA suggest that properties seen here probably are not explained by known biochemical activities of these proteins. Our results indicate that the general pattern of gene expression and, in turn, the ability of Escherichia coli to grow under a defined condition are the result of a complex interplay between GreA, GreB, and DksA that also involves mutual control of their gene expression, competition for RNA polymerase binding, and similar or opposite action on RNA polymerase activity. PMID- 22056928 TI - Activation of the cryptic PhnE permease promotes rapid adaptive evolution in a population of Escherichia coli K-12 starved for phosphate. AB - Escherichia coli K-12 suffers acetic acid stress during prolonged incubation in glucose minimal medium containing a limiting concentration of inorganic phosphate (0.1 mM P(i)), which decreases the number of viable cells from 6 * 10(8) to <=10 CFU/ml between days 6 and 14 of incubation. Here we show that following two serial transfers into P(i)-limiting medium, evolved mutants survived prolonged incubation (~10(7) CFU/ml on day 14 of incubation). The evolved strains that overtook the populations were generally PhnE(+), whereas the ancestral K-12 strain carries an inactive phnE allele, which prevents the transport of phosphonates. The switching in phnE occurred with a high frequency as a result of the deletion of an 8-bp repeated sequence. In a mixed culture starved for P(i) that contained the K-12 ancestral strain in majority, evolved strains grew through PhnE-dependent scavenging of probably organic phosphate esters (not phosphonates or P(i)) released by E. coli K-12 between days 1 and 3, before acetic acid excreted by E. coli K-12 reached toxic levels. The growth yield of phnE(+) strains in mixed culture was dramatically enhanced by mutations that affect glucose metabolism, such as an rpoS mutation inactivating the alternative sigma factor RpoS. The long-term viability of evolved populations was generally higher when the ancestral strain carried an inactive rather than an active phnE allele, which indicates that cross-feeding of phosphorylated products as a result of the phnE polymorphism may be essential for the spread of mutants which eventually help populations to survive under P(i) starvation conditions. PMID- 22056929 TI - A Rickettsia genome overrun by mobile genetic elements provides insight into the acquisition of genes characteristic of an obligate intracellular lifestyle. AB - We present the draft genome for the Rickettsia endosymbiont of Ixodes scapularis (REIS), a symbiont of the deer tick vector of Lyme disease in North America. Among Rickettsia species (Alphaproteobacteria: Rickettsiales), REIS has the largest genome sequenced to date (>2 Mb) and contains 2,309 genes across the chromosome and four plasmids (pREIS1 to pREIS4). The most remarkable finding within the REIS genome is the extraordinary proliferation of mobile genetic elements (MGEs), which contributes to a limited synteny with other Rickettsia genomes. In particular, an integrative conjugative element named RAGE (for Rickettsiales amplified genetic element), previously identified in scrub typhus rickettsiae (Orientia tsutsugamushi) genomes, is present on both the REIS chromosome and plasmids. Unlike the pseudogene-laden RAGEs of O. tsutsugamushi, REIS encodes nine conserved RAGEs that include F-like type IV secretion systems similar to that of the tra genes encoded in the Rickettsia bellii and R. massiliae genomes. An unparalleled abundance of encoded transposases (>650) relative to genome size, together with the RAGEs and other MGEs, comprise ~35% of the total genome, making REIS one of the most plastic and repetitive bacterial genomes sequenced to date. We present evidence that conserved rickettsial genes associated with an intracellular lifestyle were acquired via MGEs, especially the RAGE, through a continuum of genomic invasions. Robust phylogeny estimation suggests REIS is ancestral to the virulent spotted fever group of rickettsiae. As REIS is not known to invade vertebrate cells and has no known pathogenic effects on I. scapularis, its genome sequence provides insight on the origin of mechanisms of rickettsial pathogenicity. PMID- 22056930 TI - Characterization of the Escherichia coli SecA signal peptide-binding site. AB - SecA signal peptide interaction is critical for initiating protein translocation in the bacterial Sec-dependent pathway. Here, we have utilized the recent nuclear magnetic resonance (NMR) and Forster resonance energy transfer studies that mapped the location of the SecA signal peptide-binding site to design and isolate signal peptide-binding-defective secA mutants. Biochemical characterization of the mutant SecA proteins showed that Ser226, Val310, Ile789, Glu806, and Phe808 are important for signal peptide binding. A genetic system utilizing alkaline phosphatase secretion driven by different signal peptides was employed to demonstrate that both the PhoA and LamB signal peptides appear to recognize a common set of residues at the SecA signal peptide-binding site. A similar system containing either SecA-dependent or signal recognition particle (SRP)-dependent signal peptides along with the prlA suppressor mutation that is defective in signal peptide proofreading activity were employed to distinguish between SecA residues that are utilized more exclusively for signal peptide recognition or those that also participate in the proofreading and translocation functions of SecA. Collectively, our data allowed us to propose a model for the location of the SecA signal peptide-binding site that is more consistent with recent structural insights into this protein translocation system. PMID- 22056931 TI - Characterization of DNA sequences required for the CcrAB-mediated integration of staphylococcal cassette chromosome mec, a Staphylococcus aureus genomic island. AB - The mobile element staphylococcal cassette chromosome mec (SCCmec), which carries mecA, the gene responsible for methicillin resistance in staphylococci, inserts into the chromosome at a specific site, attB, mediated by serine recombinases, CcrAB and CcrC, encoded on the element. This study sought to determine the sequence specificity for CcrB DNA binding in vitro and for CcrAB-mediated SCCmec insertion in vivo. CcrB DNA binding, as assessed in vitro by electrophoretic mobility shift assay (EMSA), revealed that a 14-bp sequence (CGTATCATAAGTAA; the terminal sequence of the orfX gene) was the minimal requirement for binding, containing an invariant sequence (TATCATAA) found in all chromosomal (attB) and SCCmec (attS) integration sites. The sequences flanking the minimal attB and attS binding sites required for insertion in vivo were next determined. A plasmid containing only 37 bp of attS and flanking sequences was required for integration into the attB site at 92% efficiency. In contrast, at least 200 bp of sequence within orfX, 5' to the attB core, and 120 bp of specific sequence 3' to the orfX stop site and attB core were required for the highest insertion frequency. Finally, an attS-containing plasmid was inserted into wild-type Staphylococcus aureus strains without integrated SCCmec (methicillin susceptible) at various frequencies which were determined both by sequences flanking the att site and by the presence of more than one att site on either the chromosome or the integration plasmid. This sequence specificity may play a role in the epidemiology of SCCmec acquisition. PMID- 22056932 TI - Network identification and flux quantification of glucose metabolism in Rhodobacter sphaeroides under photoheterotrophic H(2)-producing conditions. AB - The nonsulfur purple bacteria that exhibit unusual metabolic versatility can produce hydrogen gas (H(2)) using the electrons derived from metabolism of organic compounds during photoheterotrophic growth. Here, based on (13)C tracer experiments, we identified the network of glucose metabolism and quantified intracellular carbon fluxes in Rhodobacter sphaeroides KD131 grown under H(2) producing conditions. Moreover, we investigated how the intracellular fluxes in R. sphaeroides responded to knockout mutations in hydrogenase and poly-beta hydroxybutyrate synthase genes, which led to increased H(2) yield. The relative contribution of the Entner-Doudoroff pathway and Calvin-Benson-Bassham cycle to glucose metabolism differed significantly in hydrogenase-deficient mutants, and this flux change contributed to the increased formation of the redox equivalent NADH. Disruption of hydrogenase and poly-beta-hydroxybutyrate synthase resulted in a significantly increased flux through the phosphoenolpyruvate carboxykinase and a reduced flux through the malic enzyme. A remarkable increase in the flux through the tricarboxylic acid cycle, a major NADH producer, was observed for the mutant strains. The in vivo regulation of the tricarboxylic acid cycle flux in photoheterotrophic R. sphaeroides was discussed based on the measurements of in vitro enzyme activities and intracellular concentrations of NADH and NAD(+). Overall, our results provide quantitative insights into how photoheterotrophic cells manipulate the metabolic network and redistribute intracellular fluxes to generate more electrons for increased H(2) production. PMID- 22056933 TI - Rhodobacter sphaeroides uses a reductive route via propionyl coenzyme A to assimilate 3-hydroxypropionate. AB - 3-Hydroxypropionate is a product or intermediate of the carbon metabolism of organisms from all three domains of life. However, little is known about how carbon derived from 3-hydroxypropionate is assimilated by organisms that can utilize this C(3) compound as a carbon source. This work uses the model bacterium Rhodobacter sphaeroides to begin to elucidate how 3-hydroxypropionate can be incorporated into cell constituents. To this end, a quantitative assay for 3 hydroxypropionate was developed by using recombinant propionyl coenzyme A (propionyl-CoA) synthase from Chloroflexus aurantiacus. Using this assay, we demonstrate that R. sphaeroides can utilize 3-hydroxypropionate as the sole carbon source and energy source. We establish that acetyl-CoA is not the exclusive entry point for 3-hydroxypropionate into the central carbon metabolism and that the reductive conversion of 3-hydroxypropionate to propionyl-CoA is a necessary route for the assimilation of this molecule by R. sphaeroides. Our conclusion is based on the following findings: (i) crotonyl-CoA carboxylase/reductase, a key enzyme of the ethylmalonyl-CoA pathway for acetyl CoA assimilation, was not essential for growth with 3-hydroxypropionate, as demonstrated by mutant analyses and enzyme activity measurements; (ii) the reductive conversion of 3-hydroxypropionate or acrylate to propionyl-CoA was detected in cell extracts of R. sphaeroides grown with 3-hydroxypropionate, and both activities were upregulated compared to the activities of succinate-grown cells; and (iii) the inactivation of acuI, encoding a candidate acrylyl-CoA reductase, resulted in a 3-hydroxypropionate-negative growth phenotype. PMID- 22056934 TI - BpsR modulates Bordetella biofilm formation by negatively regulating the expression of the Bps polysaccharide. AB - Bordetella bacteria are Gram-negative respiratory pathogens of animals, birds, and humans. A hallmark feature of some Bordetella species is their ability to efficiently survive in the respiratory tract even after vaccination. Bordetella bronchiseptica and Bordetella pertussis form biofilms on abiotic surfaces and in the mouse respiratory tract. The Bps exopolysaccharide is one of the critical determinants for biofilm formation and the survival of Bordetella in the murine respiratory tract. In order to gain a better understanding of regulation of biofilm formation, we sought to study the mechanism by which Bps expression is controlled in Bordetella. Expression of bpsABCD (bpsA-D) is elevated in biofilms compared with levels in planktonically grown cells. We found that bpsA-D is expressed independently of BvgAS. Subsequently, we identified an open reading frame (ORF), BB1771 (designated here bpsR), that is located upstream of and in the opposite orientation to the bpsA-D locus. BpsR is homologous to the MarR family of transcriptional regulators. Measurement of bpsA and bpsD transcripts and the Bps polysaccharide levels from the wild-type and the DeltabpsR strains suggested that BpsR functions as a repressor. Consistent with enhanced production of Bps, the bpsR mutant displayed considerably more structured biofilms. We mapped the bpsA-D promoter region and showed that purified BpsR protein specifically bound to the bpsA-D promoter. Our results provide mechanistic insights into the regulatory strategy employed by Bordetella for control of the production of the Bps polysaccharide and biofilm formation. PMID- 22056935 TI - Unified nomenclature for genes involved in prokaryotic aerobic arsenite oxidation. PMID- 22056936 TI - Roles of endonuclease V, uracil-DNA glycosylase, and mismatch repair in Bacillus subtilis DNA base-deamination-induced mutagenesis. AB - The disruption of ung, the unique uracil-DNA-glycosylase-encoding gene in Bacillus subtilis, slightly increased the spontaneous mutation frequency to rifampin resistance (Rif(r)), suggesting that additional repair pathways counteract the mutagenic effects of uracil in this microorganism. An alternative excision repair pathway is involved in this process, as the loss of YwqL, a putative endonuclease V homolog, significantly increased the mutation frequency of the ung null mutant, suggesting that Ung and YwqL both reduce the mutagenic effects of base deamination. Consistent with this notion, sodium bisulfite (SB) increased the Rif(r) mutation frequency of the single ung and double ung ywqL strains, and the absence of Ung and/or YwqL decreased the ability of B. subtilis to eliminate uracil from DNA. Interestingly, the Rif(r) mutation frequency of single ung and mutSL (mismatch repair [MMR] system) mutants was dramatically increased in a ung knockout strain that was also deficient in MutSL, suggesting that the MMR pathway also counteracts the mutagenic effects of uracil. Since the mutation frequency of the ung mutSL strain was significantly increased by SB, in addition to Ung, the mutagenic effects promoted by base deamination in growing B. subtilis cells are prevented not only by YwqL but also by MMR. Importantly, in nondividing cells of B. subtilis, the accumulations of mutations in three chromosomal alleles were significantly diminished following the disruption of ung and ywqL. Thus, under conditions of nutritional stress, the processing of deaminated bases in B. subtilis may normally occur in an error-prone manner to promote adaptive mutagenesis. PMID- 22056937 TI - The cyanobacterial NAD kinase gene sll1415 is required for photoheterotrophic growth and cellular redox homeostasis in Synechocystis sp. strain PCC 6803. AB - NAD kinase (NADK), which phosphorylates NAD to NADP, is one of the key enzymes regulating the cellular NADP(H) level. In Synechocystis sp. strain PCC 6803, slr0400 and sll1415 were shown to encode NAD kinases. The NADP(H) pool in the cyanobacterium was remarkably reduced by an sll1415-null mutation but slightly reduced by an slr0400-null mutation. The reduction of the NADP(H) level in the sll1415 mutant led to a significant accumulation of glucose-6-phosphate and a loss of photoheterotrophic growth. As the primary NADK gene, sll1415 was found to inhibit the transcription of genes involved in redox homeostasis and to exert stronger effects on methyl viologen tolerance than slr0040. PMID- 22056938 TI - Novel roles of SoxR, a transcriptional regulator from Xanthomonas campestris, in sensing redox-cycling drugs and regulating a protective gene that have overall implications for bacterial stress physiology and virulence on a host plant. AB - In Xanthomonas campestris pv. campestris, SoxR likely functions as a sensor of redox-cycling drugs and as a transcriptional regulator. Oxidized SoxR binds directly to its target site and activates the expression of xcc0300, a gene that has protective roles against the toxicity of redox-cycling compounds. In addition, SoxR acts as a noninducible repressor of its own expression. X. campestris pv. campestris requires SoxR both for protection against redox-cycling drugs and for full virulence on a host plant. The X. campestris model of the gene regulation and physiological roles of SoxR represents a novel variant of existing bacterial SoxR models. PMID- 22056939 TI - Survival in a German population with frontotemporal lobar degeneration. AB - BACKGROUND: The present study aimed at analysing survival of patients with behavioural-variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA). Furthermore, the objective of the study was to identify prognostic factors associated with survival and to examine causes of death. METHODS: Interviews were performed with the proxies of 124 patients with frontotemporal lobar degeneration (FTLD). RESULTS: Survival from the onset of first symptoms was significantly longer in SD than in bvFTD (10.5 years). Median survival in PNFA was 12.6 years. Age at onset, gender, education and severity of dementia at diagnosis did not significantly influence survival. We did not identify any phenocopy cases. The most frequent cause of death as reported by caregivers was respiratory system disorder. CONCLUSION: This study adds to the growing literature on survival in patients with FTLD and provides insights into the causes of death. PMID- 22056940 TI - The role of the sub-thalamic nucleus in the preparation of volitional movement termination in Parkinson's disease. AB - The sub-thalamic nucleus (STN) is relevant to the preparation of movement ignition but its role in movement termination is uncertain. Fourteen patients with Parkinson's disease (PD) received local field potentials (LFPs) recording at the left STN on the fourth day after deep brain stimulation surgery. They performed phasic and tonic movements of the right wrist extensor. Movement onset (Mon) and movement offset (Moff) of the electromyographic activities were used as triggers to determine an eight-second LFPs epoch for time-frequency analysis. Movement-related power changes were assessed by repeated measures analysis of variance with within-subject factors of Event (Mon and Moff), Period (ten time periods for phasic movement and six time periods for tonic movement), and Frequency (alpha, low-beta, and high-beta). There was significant triple interaction in both the phasic and tonic movements. By post-hoc analysis, high beta event-related de-synchronization (ERD) appeared earlier (3s prior to Mon) than those of low-beta and alpha for the Mon phasic movement. There was no alpha ERD for the Mon tonic movement. Alpha, low-beta, and high-beta ERD all appeared about 1s prior to the Moff tonic movement. The current findings suggest that STN participates in the preparation of volitional movement termination but via a different mechanism from that in movement initiation. Unlike asynchronous ERD frequency bands present in movement initiation, a simultaneous ERD across wide frequency bands in STN may play a pivotal role in terminating volitional movement. PMID- 22056941 TI - A continuous high frequency stimulation of the subthalamic nucleus determines a suppression of excitatory synaptic transmission in nigral dopaminergic neurons recorded in vitro. AB - High frequency stimulation of the subthalamic nucleus (HFS-STN) has been successfully introduced to treat symptoms of advanced Parkinson's disease (PD) (rigidity, tremor and akinesia). In spite of its extensive clinical practice, little is known at cellular level about the effects of a continuous train of electrical stimuli (>100 Hz) delivered in the STN. In this manuscript we examine the synaptic responses of substantia nigra pars compacta (SNpc) dopaminergic cells, upon continuous HFS-STN delivered in a rat brain slice preparation. We report that HFS-STN, delivered at frequencies resembling those used during DBS (100-130 Hz), caused synaptic responses in SNpc dopaminergic neurons, which summated progressively, until they reached a plateau within few tens of ms. However, if the HFS was maintained, a rapid fading of the synaptic response was observed, with an almost complete loss after 10s. Accordingly, the postsynaptic excitability, evaluated by the tonic firing rate of the SNpc dopaminergic neurons, remained unaltered during a continuous HFS-STN. Upon HFS termination, there was a rapid recovery of synaptic function. Neither a converging synaptic input, evoked by intranigral stimulation, nor the depolarizing responses to locally-applied AMPA, were affected during HFS. The loss of synaptic response by continuous HFS-STN was not prevented by inhibition of AMPA receptor desensitization, nor by antagonists of a variety of neurotransmitter receptors, known to depress synaptic transmission in the SNpc. We conclude that a HFS in the STN, with patterns resembling in vivo DBS, induces a rapid and input-specific suppression of the synaptic transmission from STN to SNpc dopaminergic neurons, that is maintained during an ongoing stimulation. The deficit of transmission between the STN and the SNpc could have a role in the therapeutic effects of the DBS procedure. PMID- 22056942 TI - Cloning and expression analysis of the mitochondrial ubiquitin ligase activator of NF-kappaB (MULAN) in Atlantic salmon (Salmo salar). AB - Nuclear factor-kappaB (NF-kappaB) is a transcription factor involved in the regulation of a large number of genes including many involved in bacterial and viral infections. NF-kappaB is normally sequestered by inhibitory proteins (IkappaBs) in the cytoplasm of non-stimulated cells. The degradation of IkappaBs by the ubiquitin proteasome pathway leads to the rapid translocation of NF-kappaB to the nucleous where it regulates gene transcription. The Mitochondrial Ubiquitin Ligase Activator of NF-kappaB, (MULAN), is an E3 ubiquitin ligase believed to be central in controlling activation of NF-kappaB, and regulating the mitochondrial dynamics and apoptosis process. We report, for the first time in fish, the characterization of a MULAN cDNA in Atlantic salmon and rainbow trout. The salmonid MULAN sequences encode predicted proteins of 352 amino acids. The mRNA of MULAN was expressed in multiple tissues, with the highest abundance in brain and white muscle. An Aeromonas salmonicida bacterial challenge increased expression of this gene in head kidney, liver and gill both at 6 and at 24h following the infection. In vitro experiments using the salmonid cell line RTG-2 indicated MULAN was increased in expression following 4h stimulation with LPS and recombinant trout IL-1beta. MULAN expression remained increased 24h post stimulation with both LPS and IL-1beta, but was down regulated by PolyI:C at this time. These results suggest an active role of the MULAN gene in the activation of the NF-kappaB pathway during piscine immune responses. PMID- 22056943 TI - Evolution of coordinated mutagenesis and somatic hypermutation in VH5. AB - The VH5 human antibody gene was analyzed using a computer program (mfg) which simulates transcription, to better understand transcription-driven mutagenesis events that occur during "phase 1" of somatic hypermutation. Results show that the great majority of mutations in the non-transcribed strand occur within loops of two predicted high-stability stem-loop structures, termed SLSs 14.9 and 13.9. In fact, 89% of the 2505 mutations reported are within the encoded complementarity-determining region (CDR) and occur in loops of these high stability structures. In vitro studies were also done and verified the existence of SLS 14.9. Following the formation of SLSs 14.9 and 13.9, a sustained period of transcriptional activity occurs within a window size of 60-70 nucleotides. During this period, the stability of these two SLSs does not change, and may provide the substrate for base exchanges and mutagenesis. The data suggest that many mutable bases are exposed simultaneously at pause sites, allowing for coordinated mutagenesis. PMID- 22056944 TI - Think androgen deficiency. PMID- 22056945 TI - Semi-automated methods for simulation and measurement of amyloid fiber distributions obtained from transmission electron microscopy experiments. AB - Transmission electron microscopy (TEM) is the standard procedure for qualitatively confirming the presence of amyloid fibers in a protein aggregation reaction product. However, extracting quantitative information about the amyloid size distribution from the electron micrographs is a nontrivial problem. Here we describe methods for (i) the simulation of pseudo-TEM images of amyloid fiber distributions having known characteristic properties and (ii) the semi-automated processing of experimental TEM images of amyloid fibers to produce two dimensional histogram plots reflecting either the distribution of amyloid length and width or, alternatively, the distribution of width and fiber rigidity/persistence. The processing method is fully automatic when the density of fibers on the grid is sufficiently low (such that the adsorbed fibers do not touch) and is semi-automatic (requiring some user decision making) when the fibers are overlapping. Termed "ADM" (for Amyloid Distribution Measurement), the program suite is written in MATLAB code and is available on request from the author. PMID- 22056946 TI - Proteomic tools for the investigation of human hair structural proteins and evidence of weakness sites on hair keratin coil segments. AB - Human hair is principally composed of hair keratins and keratin-associated proteins (KAPs) that form a complex network giving the hair its rigidity and mechanical properties. However, during their growth, hairs are subject to various treatments that can induce irreversible damage. For a better understanding of the human hair protein structures, proteomic mass spectrometry (MS)-based strategies could assist in characterizing numerous isoforms and posttranslational modifications of human hair fiber proteins. However, due to their physicochemical properties, characterization of human hair proteins using classical proteomic approaches is still a challenge. To address this issue, we have used two complementary approaches to analyze proteins from the human hair cortex. The multidimensional protein identification technology (MudPit) approach allowed identifying all keratins and the major KAPs present in the hair as well as posttranslational modifications in keratins such as cysteine trioxidation, lysine, and histidine methylation. Then two-dimensional gel electrophoresis coupled with MS (2-DE gel MS) allowed us to obtain the most complete 2-DE gel pattern of human hair proteins, revealing an unexpected heterogeneity of keratin structures. Analyses of these structures by differential peptide mapping have brought evidence of cleaved species in hair keratins and suggest a preferential breaking zone in alpha-helical segments. PMID- 22056947 TI - Development of a time-resolved fluorescence resonance energy transfer assay for cyclin-dependent kinase 4 and identification of its ATP-noncompetitive inhibitors. AB - Protein kinases are recognized as important drug targets due to the pivotal roles they play in human disease. Many kinase inhibitors are ATP competitive, leading to potential problems with poor selectivity and significant loss of potency in vivo due to cellular ATP concentrations being much higher than K(m). Consequently, there has been growing interest in the development of ATP noncompetitive inhibitors to overcome these problems. There are challenges to identifying ATP-noncompetitive inhibitors from compound library screens because ATP-noncompetitive inhibitors are often weaker and commonly excluded by potency based hit selection criteria in favor of abundant and highly potent ATP competitive inhibitors in screening libraries. Here we report the development of a time-resolved fluorescence resonance energy transfer (TR-FRET) assay for protein kinase cyclin-dependent kinase 4 (CDK4) and the identification of ATP noncompetitive inhibitors by high-throughput screening after employing a strategy to favor this type of inhibitors. We also present kinetic characterization that is consistent with the proposed mode of inhibition. PMID- 22056948 TI - Risk for advanced-stage endometrial cancer in surgical specimens from patients with complex endometrial hyperplasia with atypia. AB - OBJECTIVES: To determine the incidence of endometrial cancer in patients undergoing hysterectomy for atypical complex endometrial hyperplasia and to study the risk of advanced endometrial cancer that may be associated with extra-uterine disease. METHODS: A retrospective chart review was performed of the records of all women who underwent hysterectomy for a preoperative diagnosis of complex hyperplasia with atypia from two teaching hospitals between 1999 and 2006. Demographic and clinical variables were collected and analyzed for the 80 patients identified by the initial screening methods. RESULTS: After screening and exclusions, 66 women with a preoperative diagnosis of atypical complex hyperplasia who subsequently underwent a hysterectomy were identified. Eleven of the 66 patients with atypical complex hyperplasia had a diagnosis of endometrial carcinoma in the hysterectomy specimens (17%). No endometrial cancer patient was staged greater than stage 1B or had greater than grade 2 disease. The patients with endometrial cancer were older (p < 0.05). Evidence of myometrial invasion was found in 63% (7/11) of the cancer cases, but all were less than 50% of the myometrium. CONCLUSION: Endometrial cancer found at the time of hysterectomy for complex hyperplasia with atypia may be associated with less advanced disease. PMID- 22056949 TI - The clinical impact of the couch top and rails on IMRT and arc therapy. AB - The clinical impact of the Varian Exact Couch on dose, volume coverage to targets and critical structures, and tumor control probability (TCP) has not been described. Thus, we examined their effects on IMRT and arc therapy. Five clinical prostate patients were planned with both 6 MV eight-field IMRT and 6 MV two-arc RapidArc techniques using the Eclipse treatment planning system. These plans neglected treatment couch attenuation, as is a common clinical practice. Dose distributions were then recalculated in Eclipse with the inclusion of the Varian Exact Couch (imaging couch top) and the rails in varying configurations. The changes in dose and coverage were evaluated using the dose-volume histograms from each plan iteration. We used a TCP model to calculate losses in tumor control resulting from not accounting for the couch top and rails. We also verified dose measurements in a phantom. Failure to account for the treatment couch and rails resulted in clinically unacceptable dose and volume coverage losses to the targets for both IMRT and RapidArc. The couch caused average prescription dose losses (relative to plans that ignored the couch) to the prostate of 4.2% and 2.0% for IMRT with the rails out and in, respectively, and 3.2% and 2.9% for RapidArc with the rails out and in, respectively. On average, the percentage of the target covered by the prescribed dose dropped to 35% and 84% for IMRT (rails out and in, respectively) and to 18% and 17% for RapidArc (rails out and in, respectively). The TCP was also reduced by as much as 10.5% (6.3% on average). Dose and volume coverage losses for IMRT plans were primarily due to the rails, while the imaging couch top contributed most to losses for RapidArc. Both the couch top and rails contribute to dose and coverage losses that can render plans clinically unacceptable. A follow-up study we performed found that the less attenuating unipanel mesh couch top available with the Varian Exact couch does not cause a clinically impactful loss of dose or coverage for IMRT but still causes an unacceptable loss for RapidArc. Therefore, both the imaging or mesh couch top and the rails should be accounted for in arc therapy. The imaging couch top should be accounted for in IMRT treatment planning or the mesh top can be used, which would not need to be accounted for, and the rails should be moved to avoid the beams during treatment. PMID- 22056950 TI - Attenuation of LPS-induced inflammation by ICT, a derivate of icariin, via inhibition of the CD14/TLR4 signaling pathway in human monocytes. AB - OBJECTIVE: To evaluate the anti-inflammatory potential of ICT in LPS stimulated human innate immune cells. BACKGROUND: 3, 5, 7-Trihydroxy-4'-methoxy-8-(3-hydroxy 3- methylbutyl)-flavone (ICT) is a novel derivative of icariin, the major active ingredient of Herba Epimedii, an herb used in traditional Chinese medicine. We previously demonstrated its anti-inflammatory potential in a murine macrophage cell line as well as in mouse models. METHODS: We measured TNF-alpha production by ELISA, TLR4/CD14 expression by flow cytometry, and NF-kappaB and MAPK activation by western blot all in LPS-stimulated PBMC, human monocytes, or THP-1 cells after treatment with ICT. RESULTS: ICT inhibited LPS-induced TNF-alpha production in THP-1 cells, PBMCs and human monocytes in a dose-dependent manner. ICT treatment resulted in down-regulation of the expression of CD14/TLR4 and attenuated NF-kappaB and MAPK activation induced by LPS. CONCLUSION: We illustrate the anti-inflammatory property of ICT in human immune cells, especially in monocytes. These effects were mediated, at least partially, via inhibition of the CD14/TLR4 signaling pathway. PMID- 22056951 TI - Stem cell pathologies and neurological disease. AB - The presence of stem and progenitor cells in the adult human brain suggests a putative and persistent role in reparative behaviors following neurological injury and neurological disease. Too few stem/progenitor cells (as in the case of Parkinson's disease) or too many of these cells (as in the case of Huntington's disease and glioma) could contribute to and even signal brain pathology. We address here critical issues faced by the field of stem cell biology and regenerative medicine, arguing from well-documented as well as speculative perspectives for a potential role for stem cells in the pathology of many human neurological diseases. Although stem cell responses may result in regenerative failure, in many cases they may help in the establishment or re-establishment of a functional neural circuitry (eg, after stroke). Therefore, we would argue that stem cells have a crucial-either positive or negative-role in the pathology of many neurological diseases. PMID- 22056952 TI - MYC gene amplification is often acquired in lethal distant breast cancer metastases of unamplified primary tumors. AB - In breast cancer, amplification of MYC is consistently observed in aggressive forms of disease and correlates with poor prognosis and distant metastases. However, to date, a systematic analysis of MYC amplification in metastatic breast cancers has not been reported. Specifically, whether the MYC amplification status may change in metastases in comparison to the corresponding primary breast tumor, and potential variability among different metastases within the same patient have also not been assessed. We generated single patient tissue microarrays consisting of both primary breast carcinomas and multiple matched systemic metastases from 15 patients through our previously described rapid autopsy program. In total, the 15 tissue microarrays contained 145 primary tumor spots and 778 spots derived from 180 different metastases. In addition, two separate tissue microarrays were constructed composed of 10 matched primary breast cancers and corresponding solitary metastases sampled not at autopsy but rather in routine surgical resections. These two tissue microarrays totaled 50 primary tumor spots and 86 metastatic tumor spots. For each case, hormone receptor status, HER2/neu, EGFR and CK5/6 expression were assessed, and the cases were characterized as luminal, basal-like or HER2 based on published criteria. Both fluorescence in situ hybridization and immunohistochemistry for MYC was performed on all cases. Of the 25 cases, 24 were evaluable. While 4 of 24 primary tumors (16%) demonstrated MYC amplification, an additional 6 (25% of total evaluable cases) acquired MYC amplification in their systemic metastases. Of note, there was remarkably little heterogeneity in MYC copy number among different metastases from the same patient. MYC immunoreactivity was increased in metastases relative to matched primaries in the surgical cohort, although there was no perfect correlation with MYC amplification. In conclusion, amplification of MYC is a frequent event in breast cancer, but occurs more frequently as a diffuse, acquired event in metastatic disease than in the corresponding primary. These observations underscore the importance of MYC in breast cancer progression/metastasis, as well as its relevance as a potential therapeutic target in otherwise incurable metastatic disease. PMID- 22056953 TI - Molecular subtyping of male breast cancer by immunohistochemistry. AB - Molecular subtyping of breast cancer by gene expression has proven its significance in females. Immunohistochemical surrogates have been used for this classification, because gene expression profiling is not yet routinely feasible. Male breast cancer is rare and large series are lacking. In this study, we used immunohistochemistry for molecular subtyping of male breast cancer. A total of 134 cases of male breast cancer were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor (PR), HER2 and epidermal growth factor receptor (EGFR), as well as for CK5/6, CK14, and Ki67. HER2 was also assessed by chromogen in situ hybridization. Cases were classified as luminal A (ER+ and/or PR+, and HER2- and Ki67 low), luminal B (ER+ and/or PR+, and HER2+ or Ki67 high), HER2 driven (ER-, PR-, HER2+), basal-like (ER-, PR-, HER2-, CK5/6+ and/or CK14+ and/or EGFR+), or unclassifiable triple-negative (negative for all six markers). Luminal type A was by far the most encountered type of male breast cancers, representing 75% of the cases. Luminal type B was seen in 21% and the remaining 4% of cases were classified as basal-like (n=4) and unclassifiable triple-negative (n=1). No HER2 driven cases were identified. Patients with basal-like cancer were significantly younger (P=0.034). Luminal B type cancers showed significantly higher histological grade (P<0.001), mitotic index (P<0.001), and PR negativity (P=0.005) compared with luminal type A cancers. In conclusion, most male breast cancers are luminal A and luminal B types, whereas basal-like, unclassifiable triple-negative, and HER2 driven male breast cancers are rare. Luminal type B seem to represent a subtype with an aggressive phenotype. This distribution of molecular subtypes in male breast cancer is clearly different compared with female breast cancers, pointing to possible important differences in carcinogenesis. PMID- 22056954 TI - Large duct type invasive adenocarcinoma of the pancreas with microcystic and papillary patterns: a potential microscopic mimic of non-invasive ductal neoplasia. AB - A morphological variant of pancreatic ductal adenocarcinoma forming large ductal elements, large duct type ductal adenocarcinoma, is documented and its clinicopathological features are studied. These tumors may have microcystic and papillary growth patterns that closely mimic the non-invasive cystic and papillary pancreatic tumors such as: intraductal papillary-mucinous neoplasia, including the oncocytic variant, mucinous cystic neoplasms, and ducts involved by pancreatic intraepithelial neoplasia. In a review of 230 pancreatectomy specimens with ductal adenocarcinoma, 28 (8%) cases of large duct type ductal adenocarcinomas were identified according to following criteria: more than 50% of the tumor sections available for examination contained infiltrative ducts with a diameter larger than 0.5 mm or had a macroscopically identifiable microcystic pattern. Overall characteristics of large duct type ductal adenocarcinomas were not too different than those of conventional ductal adenocarcinomas, except that there was a slight female predominance in the former (F/M=2.3). The mean age was 67 (vs 63 in conventional ductal adenocarcinomas; P=0.015), and occurrence in the tail was slightly more common (40% vs 18% in conventional ductal adenocarcinomas; P=0.006). Grossly, cysts measuring up to 1 cm was noted in 10 cases. Microscopically, large duct type adenocarcinomas were characterized by irregularly distributed large ducts with jagged edges, lined by columnar mucinous cells often having deceptively bland cytological features and variable degrees of papillomatosis. Stromal desmoplasia had a hypercellular quality (morphologically distinct from ovarian-like stroma) in four cases, and had a myxoid quality in others. KRAS oncogene mutation was identified in 9 out of 11 cases. Median, 1 year and 2-year survival rates were 16 months, 77% and 30%, respectively, as opposed to 12 months, 52% and 30%, respectively, in conventional ductal adenocarcinoma. In conclusion, it should be recognized that, some (8%) pancreatic ductal adenocarcinomas exhibit a large duct pattern that may microscopically mimic non-invasive pancreatic tumors characterized by cystic and papillary patterns. They may be distinguished by the relatively smaller size of the cysts, irregularity of the duct contours, clustering of the ducts, presence of intraluminal neutrophils and granular debris, degree of cytological pleomorphism, and myxoid quality of the stroma. Clinical behavior appears to be slightly better than that of conventional ductal adenocarcinoma, which may be accounted by the well-differentiated nature of these tumors. PMID- 22056955 TI - p40 (DeltaNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. AB - Immunohistochemistry has recently emerged as a powerful ancillary tool for differentiating lung adenocarcinoma and squamous cell carcinoma-a distinction with important therapeutic implications. Although the most frequently recommended squamous marker p63 is extremely sensitive, it suffers from low specificity due to its reactivity in a substantial proportion of lung adenocarcinomas and other tumor types, particularly lymphomas. p40 is a relatively unknown antibody that recognizes DeltaNp63-a p63 isoform suggested to be highly specific for squamous/basal cells. Here we compared the standard p63 antibody (4A4) and p40 in a series of 470 tumors from the archives of Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Hospital, which included lung squamous cell carcinomas (n=81), adenocarcinomas (n=237), and large cell lymphomas (n=152). The p63 was positive in 100% of squamous cell carcinomas, 31% of adenocarcinomas, and 54% of large cell lymphomas (sensitivity 100%, specificity 60%). In contrast, although p40 was also positive in 100% of squamous cell carcinomas, only 3% of adenocarcinomas, and none of large cell lymphomas had p40 labeling (sensitivity 100%, specificity 98%). The mean percentage of p63 versus p40-immunoreactive cells in squamous cell carcinomas was equivalent (97 vs 96%, respectively, P=0.73). Rare adenocarcinomas with p40 labeling had reactivity in no more than 5% of tumor cells, whereas the mean (range) of p63-positive cells in adenocarcinomas and lymphomas was 26% (1-90%) and 48% (2-100%), respectively. In summary, p40 is equivalent to p63 in sensitivity for squamous cell carcinoma, but it is markedly superior to p63 in specificity, which eliminates a potential pitfall of misinterpreting a p63-positive adenocarcinoma or unsuspected lymphoma as squamous cell carcinoma. These findings strongly support the routine use of p40 in place of p63 for the diagnosis of pulmonary squamous cell carcinoma. PMID- 22056956 TI - Ab initio molecular dynamics model for density, elastic properties and short range order of Co-Fe-Ta-B metallic glass thin films. AB - Density, elastic modulus and the pair distribution function of Co-Fe-Ta-B metallic glasses were obtained by ab initio molecular dynamics simulations and measured for sputtered thin films using x-ray reflectivity, nanoindentation and x ray diffraction using high energy photons. The computationally obtained density of 8.19 g cm(-3) for Co(43)Fe(20)Ta(5.5)B(31.5) and 8.42 g cm(-3) for Co(45.5)Fe(24)Ta(6)B(24.5), as well as the Young's moduli of 273 and 251 GPa, respectively, are consistent with our experiments and literature data. These data, together with the good agreement between the theoretical and the experimental pair distribution functions, indicate that the model established here is useful to describe the density, elasticity and short range order of Co-Fe Ta-B metallic glass thin films. Irrespective of the investigated variation in chemical composition, (Co, Fe)-B cluster formation and Co-Fe interactions are identified by density-of-states analysis. Strong bonds within the structural units and between the metallic species may give rise to the comparatively large stiffness. PMID- 22056957 TI - The pre-synaptic metabotropic glutamate receptor 7 "mGluR7" is a critical modulator of ethanol sensitivity in mice. AB - Recent studies demonstrated that the metabotropic glutamate receptor subtype 7 "mGluR7" activation may reduce motivational aspects of ethanol dependence. We investigated the role of mGlu7 receptor in ethanol-related behaviors using the allosteric agonist AMN082 in mice. Results have shown that mGluR7 activation increased the sedative effect of ethanol as measured by the duration of loss of righting reflex (LORR) and reduced the severity of ethanol-induced withdrawal. Importantly, the protective effect of the drug on alcohol-induced withdrawal was found when the AMN082 was injected before, but not after, injection of ethanol suggesting that mGluR7 activation prevented development of dependence rather than producing an anti-convulsant effect. In addition, ethanol-induced locomotor stimulation was blocked by following mGluR7 activation. Furthermore, mice injected with AMN082 consumed less ethanol in a two-bottle free-choice paradigm and in a drinking in the dark (DID) model. Impairment in reward mechanisms in AMN082-injected mice was confirmed by the lack of ethanol-induced conditioned place preference (CPP). Follow-up control experiments have shown that plasma alcohol concentrations of AMN082 and vehicle-treated mice were similar. Taken together, these findings provide evidence for the crucial role of mGluR7 in ethanol-related behaviors, especially in voluntary alcohol drinking and alcohol reward. Thus, pharmacological targeting mGluR7 with AMN082-like compounds might be a potential means to tackle ethanol abuse and alcoholism in the future. PMID- 22056958 TI - Orexinergic neuron numbers in three species of African mole rats with rhythmic and arrhythmic chronotypes. AB - In the present study, orexinergic cell bodies within the brains of rhythmic and arrhythmic circadian chronotypes from three species of African mole rat (Highveld mole rat-Cryptomys hottentotus pretoriae, Ansell's mole rat--Fukomys anselli and the Damaraland mole rat--Fukomys damarensis) were identified using immunohistochemistry for orexin-A. Immunopositive orexinergic (Orx+) cell bodies were stereologically assessed and absolute numbers of orexinergic cell bodies were determined for the distinct circadian chronotypes of each species of mole rat examined. The aim of the study was to investigate whether the absolute numbers of identified orexinergic neurons differs between distinct circadian chronotypes with the hypothesis of elevated hypothalamic orexinergic neurons in the arrhythmic chronotypes compared with the rhythmic chronotypes. We found statistically significant differences between the circadian chronotypes ofF. anselli, where the arrhythmic group had higher mean numbers of hypothalamic orexin neurons compared with the rhythmic group. These differences were observed when the raw data was compared and when the raw data was corrected for body mass (M(b)) and brain mass (M(br)). For the two other species investigated, no significant differences were noted between the chronotypes, although a statistically significant difference was noted between all rhythmic and arrhythmic individuals of the current study when the counts of orexin neurons were corrected for M(b)--the arrhythmic individuals had larger numbers of orexin cells. PMID- 22056959 TI - Informed decision making for in-home use of motion sensor-based monitoring technologies. AB - Motion sensor-based monitoring technologies are designed to maintain independence and safety of older individuals living alone. These technologies use motion sensors that are placed throughout older individuals' homes in order to derive information about eating, sleeping, and leaving/returning home habits. Deviations from normal behavioral patterns are detected using statistical analysis of activities of daily living. Sensors are linked to mobile devices and secure Web pages in order to transmit information to designated caregivers who live outside the home. It is difficult to make informed decisions about purchasing new technologies. This article describes elements for making informed decisions about purchasing motion sensor-based monitoring technologies and factors that could be used to evaluate these technologies. Case managers, physicians, nurses, and social workers may be asked to help older individuals and their families make informed purchasing decisions. Recommendations and practical tools are provided to best support these professionals in their dialog with older individuals and their families. PMID- 22056960 TI - The influence of consistent assignment on nursing home deficiency citations. AB - OBJECTIVE: The association of consistent assignment of nurse aides (NAs) with quality of care and quality of life of nursing home residents is examined (using 5 groups of deficiency citations). METHODS: Data used came from a survey of nursing home administrators, the Online Survey Certification and Reporting data, and the Area Resource File. The information including consistent assignment and staffing variables of registered nurses, licensed practical nurses, and NAs were measured in 2007 and came from 3,941 facilities. Negative binomial regression and multivariate logistic regression models were used. RESULTS: An average of 68% of nursing homes in this sample reported using consistent assignment. However, the actual level of NA consistent assignment used varied substantially. Only 28% of nursing homes using NA consistent assignment did so at the often recommended level of 85% (or more). In the multivariate analyses, consistent assignment was associated with the deficiency citations examined in 4 of the 5 models. That is, quality of life deficiency citations (resident), quality of life deficiency citations (staffing), quality of life deficiency citations (facility), and quality of care deficiency citations were significantly (p < .01) lower in facilities with the highest levels of consistent NA assignment. Few significant findings were found in nursing homes using lower levels of consistent assignment. CONCLUSION: Consistent assignment has developed as a preferred practice in nursing homes based on little empirical evidence in the peer-reviewed literature. The findings presented here provide some justification for the use of this staffing practice for NAs. PMID- 22056961 TI - Emergency department use by nursing home residents: effect of severity of cognitive impairment. AB - PURPOSE: To examine the 1-year prevalence and risk of emergency department (ED) use and ambulatory care-sensitive (ACS) ED use by nursing home (NH) residents with different levels of severity of cognitive impairment (CI). DESIGN AND METHODS: We used multinomial logistic regression to estimate the effect of CI severity on the odds of any ED visit and any ACS ED visit in a 2006 national random sample of NH residents, controlling for predisposing, enabling, and need characteristics. RESULTS: Of 132,753 NH residents, 62% had at least one ED visit and approximately 24% had at least one ACS ED visit in 2006. The probability of any ED visit or any ACS ED visit varied with the severity of resident CI. Residents with mild CI had up to 15% higher odds of any ED or any ACS ED visit and those with more moderate CI had 9% higher odds of an ACS ED visit compared with those without CI. The probability of any ED visit was negatively associated with advanced dementia (adjusted odds ratio = 0.60; 95% CI = 0.55-0.65). IMPLICATIONS: Earlier identification of persons with mild CI may facilitate patient, family, and staff education, as well as advanced care planning to reduce ACS ED visits. Both ACS ED use and hospitalizations, adjusted for case mix, should be used as quality indicators to help ensure greater accountability for high-quality NH care and more appropriate utilization of ED resources. PMID- 22056962 TI - Supine head tremor: a clinical comparison of essential tremor and spasmodic torticollis patients. AB - BACKGROUND: Essential tremor (ET) is among the most misdiagnosed neurological diseases, and overdiagnosis is especially common. As many as 30-50% of supposed 'ET' cases have other diagnoses, with dystonia prominent among these. Therefore, the recognition of differences in tremor phenomenology has potential diagnostic value for practising clinicians. There is an anecdotal sense that head tremor in ET is positional rather than resting, a feature which could aid in the diagnosis, yet no published data exist. METHODS: In this cross-sectional study of ET and spasmodic torticollis (ST) patients (3:1 matching) who had head tremor while upright, the prevalence of supine (ie, resting) head tremor was compared. RESULTS: There were 60 ET cases and 19 ST cases with head tremor while seated. When supine, head tremor persisted in only 5/60 (8.3%) ET versus 13/19 (68.4%) ST cases (p<0.001), indicating that essential head tremor is more likely to resolve in the supine position than is the head tremor of ST. Supine head tremor, when present in ET, did not seem to preferentially occur in patients with more severe disease (p>0.05). CONCLUSIONS: These results indicate that there is some validity to the anecdotal sense that head tremor in ET is a postural tremor that dissipates when a patient lies down; by contrast, in ST, head tremor more often persists. In a clinical context, these results have potential implications in diagnostically ambiguous patients with head tremor. Physicians should consider asking their tremor patients to lie down to assess whether head tremor resolves. PMID- 22056963 TI - Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. AB - Sporadic cerebral amyloid angiopathy (CAA) is a common age related cerebral small vessel disease, characterised by progressive deposition of amyloid-beta (Abeta) in the wall of small to medium sized arteries, arterioles and capillaries of the cerebral cortex and overlying leptomeninges. Previously considered to be a rare neurological curiosity, CAA is now recognised as an important cause of spontaneous intracerebral haemorrhage and cognitive impairment in the elderly, two fundamental challenges in the field of cerebrovascular disease. Our understanding of the pathophysiology and clinical manifestations of CAA continues to evolve rapidly, with the use of transgenic mouse models and advanced structural and/or molecular neuroimaging techniques. Yet, despite remarkable recent interest, CAA remains under-recognised by neurologists and stroke physicians. In this review, a fresh look at key developments in understanding the complex pathophysiology, important clinical and radiological features, diagnostic approaches and prospects for rational therapies for this enigmatic small vessel disorder is provided. PMID- 22056964 TI - Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). AB - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of the CNS with a predilection for the hindbrain and responsive to immunotherapy. Five further cases are described with detailed pathology and long term evaluation. CLIPPERS does not represent a benign condition, and without chronic immunosuppression the disease may relapse. The radiological distribution is focused not only in the pons but also in the brachium ponti and cerebellum. Pontocerebellar atrophy occurred early, even in cases treated promptly. Significant cognitive impairment was seen in some cases and was associated with additional cerebral atrophy. The pathology included distinctive histiocytic as well as lymphocytic components and evidence of neuro-axonal injury. Additional subclinical systemic findings on investigation were identified. Relapse was associated with withdrawal of corticosteroids, and disability was least marked in cases where both the presentation and relapses were treated promptly. We propose that the title of the syndrome be amended to chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids to more accurately reflect the distribution of the radiological findings. PMID- 22056965 TI - Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis. AB - BACKGROUND: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon beta-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. METHODS: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. RESULTS: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; >=1.0*10(9) cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (>=0.1*10(9)/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN >=0.2*10(9) cells/l) and CD4 lymphocytes (LLN >=0.4*10(9) cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. CONCLUSIONS: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection. PMID- 22056966 TI - The association between cerebral amyloid angiopathy and intracerebral haemorrhage: systematic review and meta-analysis. AB - BACKGROUND: The aim of this study was to determine the strength of the association between intracerebral haemorrhage (ICH) and cerebral amyloid angiopathy (CAA) in a systematic review of published neuropathological studies. METHODS: In April 2011, Ovid Medline (from 1950) and Embase (from 1980) were searched for neuropathological studies that quantified the prevalence of CAA in patients with ICH and in a control group without ICH. Two authors extracted data from each study and meta-analysed their results using a random effects model. RESULTS: 10 neuropathological cross sectional or case control studies were identified, involving 481 cases with ICH and 3219 controls. There was no association between CAA and ICH in any location (OR 1.21, 95% CI 0.87 to 1.68; 10 studies, I(2) 29%), deep ICH (OR 0.81, 95% CI 0.30 to 2.19; five studies, I(2) 58%) or cerebellar ICH (OR 2.05, 95% CI 0.55 to 7.63; four studies, I(2) 0%). CAA was significantly associated with lobar ICH, both overall (OR 2.21, 95% CI 1.09 to 4.45; six studies, I(2) 40%) and in the three studies where average ages for cases and controls were comparable (OR 3.24, 95% CI 1.02 to 10.26). CONCLUSIONS: There is an association between CAA and lobar ICH, although the association might be stronger if potential confounding factors, distinctive clinical and imaging features of ICH due to CAA and CAA neuropathological severity are taken into account. PMID- 22056967 TI - Functional connectivity of dissociation in patients with psychogenic non epileptic seizures. AB - INTRODUCTION: Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures, but lack epileptiform brain activity. Instead, the cause is assumed to be psychogenic. An abnormal coping strategy may be exhibited by PNES patients, as indicated by their increased tendency to dissociate. Investigation of resting state networks may reveal altered routes of information and emotion processing in PNES patients. The authors therefore investigated whether PNES patients differ from healthy controls in their resting-state functional connectivity characteristics and whether these connections are associated with the tendency to dissociate. METHODS: 11 PNES patients without psychiatric comorbidity and 12 healthy controls underwent task-related paradigms (picture-encoding and Stroop paradigms) and resting-state functional MRI (rsfMRI). Global cognitive performance was tested using the Raven's Matrices test and participants completed questionnaires for evaluating dissociation. Functional connectivity analysis on rsfMRI was based on seed regions extracted from task-related fMRI activation maps. RESULTS: The patients displayed a significantly lower cognitive performance and significantly higher dissociation scores. No significant differences were found between the picture-encoding and Stroop colour-naming activation maps between controls and patients with PNES. However, functional connectivity maps from the rsfMRI were statistically different. For PNES patients, stronger connectivity values between areas involved in emotion (insula), executive control (inferior frontal gyrus and parietal cortex) and movement (precentral sulcus) were observed, which were significantly associated with dissociation scores. CONCLUSION: The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes). PMID- 22056968 TI - Xylo-oligosaccharides inhibit pathogen adhesion to enterocytes in vitro. AB - We previously reported that the non-digestible carbohydrates inulin and apple pectin promoted Listeria monocytogenes infection in guinea pigs, whereas xylo- and galacto-oligosaccharides (XOS and GOS), prevented infection by this pathogen. In the present study, mechanisms that could explain the previous in vivo observations were explored. Mixing bacterial cultures with XOS significantly (P < 0.05) decreased the ability of two out of three strains of L. monocytogenes to adhere to Caco-2 cells. Additionally, 2 h incubation with XOS followed by washing of the bacteria significantly (P < 0.05) decreased the ability of all three strains to adhere to Caco-2 cells. Consistently, expression of the adhesion relevant genes inlA and lap was reduced by the presence of XOS. The observation that XOS inhibit the adhesion of Listeria to the intestinal epithelium in vitro may explain the reported preventive effect of XOS on Listeria infection in guinea pigs in vivo, while the preventive effect of GOS was not explicable by the assays chosen here. PMID- 22056969 TI - What is the life expectancy in frontotemporal lobar degeneration? PMID- 22056970 TI - Comparative acute toxicity from whole breast irradiation using 3-week accelerated schedule with concomitant boost and the 6.5-week conventional schedule with sequential boost for early-stage breast cancer. AB - BACKGROUND: We aimed to evaluate the incidence of acute toxicity in a 3-week accelerated radiation therapy (RT) schedule with a concomitant boost compared with the 6.5-week conventional schedule with a sequential boost for early-stage, node-negative breast cancer. MATERIALS AND METHODS: This study included the first 50 patients treated on protocol using the accelerated schedule as well as 74 patients with comparable stages of disease treated over the same period using the conventional schedule. An accelerated schedule of 40.5 Gy * 2.7 Gy/fraction to the whole breast with 4.5 Gy * 0.3 Gy/fraction concomitant boost, for a delivered total dose of 45.0 Gy * 3.0 Gy/fraction in 15 fractions to the lumpectomy site. The conventional schedule used 46.8 Gy * 1.8 Gy to the whole breast with a sequential boost of 14.0 Gy * 2.0 Gy/fraction, delivering a total dose of 60.8 Gy * 33 fractions to the lumpectomy site. The side effects observed during RT and through the initial 8 weeks after treatment were scored for acute toxicity. RESULTS: A lower incidence of >= grade 2 skin toxicity was observed among patients treated on the accelerated schedule compared with those treated on the conventional schedule (p = .0015). There was a higher incidence of breast pain among patients receiving the conventional schedule (p = .045). No significant difference in the incidence of breast edema, fatigue, or hematologic side effects was observed between the 2 groups. CONCLUSION: Our observations suggest that there is acceptable toxicity with the accelerated schedule as used in this study. Further, it is not associated with a higher risk of acute toxicity when compared with the conventional schedule. Patients in the study are being followed, and clinical outcomes will be reported as the data mature. PMID- 22056971 TI - Kidney function decline in the elderly: impact of lipoprotein-associated phospholipase A(2). AB - BACKGROUND: Whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with kidney function decline has not been well studied. METHODS: We investigated associations of Lp-PLA(2) antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as >=3 ml/min/1.73 m(2) per year. We stratified by baseline preserved GFR (>=60 ml/min/1.73 m(2)). RESULTS: Mean age was 72 +/- 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m(2) (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA(2) antigen, eGFRcys decline was faster among persons in the second, beta -0.31 (95% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles 0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp PLA(2) antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA(2) activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m(2)) at baseline. CONCLUSION: Higher levels of Lp-PLA(2) antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression. PMID- 22056972 TI - Prevalence and predictors of complementary and alternative medicine (CAM) use by men in Australian cancer outpatient services. AB - BACKGROUND: Although studies have shown that complementary and alternative medicine (CAM) use is common in cancer patients, no survey has assessed CAM use in men with a variety of cancers. In Australia, no data exist about male cancer patients' use of CAM. PATIENTS AND METHODS: A self-administered questionnaire was completed by 403 men attending four cancer outpatient services in Metropolitan Adelaide. Data were analyzed using Pearson's chi(2) tests and multivariate logistic regression analysis. RESULTS: CAMs were currently used by 52.9%, or used at some point by 61.5%, of respondents. The most popular CAM treatments were dietary supplements (36.1%), prayer (25.9%), herbs and botanicals (21.4%), and relaxation techniques/meditation (15.2%). CAM use was directed by a cancer specialist in 9.9% of respondents. Independent predictors of CAM use were metastatic cancer (P = 0.022), actively practicing religion (P = 0.008), and tertiary education (P = 0.007). CONCLUSIONS: CAM use in males is equally common across all cancer diagnoses, namely prostate, hematological malignancies, colorectal, lung, and other cancers. Oncologists should be aware that one-third of male patients modify their diet and/or search for spiritual guidance, particularly when diagnosed with metastatic cancer. PMID- 22056973 TI - Primary anti-vascular endothelial growth factor (VEGF)-refractory metastatic renal cell carcinoma: clinical characteristics, risk factors, and subsequent therapy. AB - BACKGROUND: A subset of patients treated with initial anti-vascular endothelial growth factor (VEGF) therapy exhibit progressive disease (PD) as the best response per RECIST criteria. METHODS: Data from patients with metastatic renal cell carcinoma (mRCC) treated with anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers. RESULTS: One thousand and fifty-six assessable patients received initial VEGF inhibitors and 272 (26%) of these patients had PD as best response. Initial treatment included sunitinib (n = 203), sorafenib (n = 51), or bevacizumab (n = 18). Six percent of patients were at favorable risk, 55% at intermediate risk, and 39% at poor risk. On multivariable analysis, predictors of PD were Karnofsky performance status < 80% [odds ratio (OR) = 2.3, P < 0.0001], diagnosis to treatment < 1 year (OR = 2.1, P < 0.0001), neutrophilia (OR = 1.9, P = 0.0021), thrombocytosis (OR = 1.7, P = 0.0068), and anemia (OR = 1.6, P = 0.0058). Median progression-free survival (PFS) in patients with PD versus without PD was 2.4 versus 11 months (P < 0.0001) and overall survival (OS) was 6.8 versus 29 months (P < 0.0001), respectively. One hundred and eight (40%) VEGF-refractory patients proceeded to receive further systemic therapies. Response rate, PFS, and OS for subsequent therapy were 9%, 2.5 months, and 7.4 months, respectively, with no statistical differences between patients who received VEGF versus mammalian target of rapamycin (mTOR) inhibitors. CONCLUSIONS: Primary anti-VEGF-refractory mRCC patients have a dismal prognosis. Second-line anti-mTOR and anti-VEGF agents produce similar outcomes. PMID- 22056974 TI - Trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in HER-2 non-amplified breast cancer cell lines. AB - BACKGROUND: Antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by CD56+natural killer (NK) cells may contribute to the activity of trastuzumab in HER-2-amplified tumours. In this study, we investigated the possibility that trastuzumab might induce ADCC against HER-2-non-amplified breast cancer cells. METHODS: Induction of NK cell-mediated ADCC was examined in trastuzumab-treated HER-2-non-amplified breast cancer cell lines. HER-2 protein levels were also determined in tumour and autologous normal tissue samples from patients with HER 2 negative breast cancer. RESULTS: Trastuzumab induced a significant ADCC response in the HER-2-amplified HCC1954 and SKBR3 cell lines, and in all five of the non-amplified cell lines, which had low levels of detectable HER-2 by western blot (CAL-51, CAMA-1, MCF-7, T47D, and EFM19). Trastuzumab did not induce ADCC in the K562 control cell line or MDA-MB-468, which has very low levels of HER-2 detectable by enzyme-linked immunosorbent assay (ELISA) only. HER-2 protein was detected by ELISA in 14/15 patient tumour samples classified as HER-2-non amplified. Significantly lower levels of HER-2 were detected in normal autologous tissue compared with tumour samples from the same patients. CONCLUSION: Our results suggest that HER-2-non-amplified breast cancer cells, with low but detectable levels of HER-2 protein, can bind trastuzumab and initiate ADCC. PMID- 22056975 TI - Molecular beacon-based half-adder and half-subtractor. AB - This work demonstrates two DNA-based logic circuits that behave as a half-adder and a half-subtractor. A half-adder is composed of an AND gate and an XOR gate, whereas a half-subtractor consists of an INH gate and an XOR gate. The proposed designs are inspired by molecular beacons. PMID- 22056976 TI - Biomechanical testing and material characterization for the rat large intestine: regional dependence of material parameters. AB - The function of the large bowel is to absorb water from the remaining indigestible food matter and subsequently pass useless waste material from the body, but there has been only a small amount of data in the literature on its biomechanical characteristics that would facilitate our understanding of its transport function. Our study aims to fill this gap by affording comprehensive inflation/extension data of intestinal segments from distinct areas, spanning a physiologically relevant deformation range (100-130% axial stretches and 0-15 mmHg lumen pressures). These data were characterized by the Fung-type exponential model in the thick-walled setting, showing reasonable agreement, i.e. root-mean square error ~30%. Based on optimized material parameters, i.e. a(1)=0.6 IUs from day 30 onward in the IN DNA-vaccinated group. The plasmid was identified in brains and lungs from days 3-15. The mRNA transcript was amplified in brains and lungs from days 3-30, and G-protein expression was observed in spleens, brains and lungs on days 3, 8, and 15. In all cases, a gradual decrease was observed on days 30 and 45 and absent on day 60. CONCLUSIONS: We found that Th1 type related cytokines (IL-2, IFN-gamma, and TNF-alpha) were stimulated during the first month after DNA vaccination, correlating with the proliferation assays. Also, it was associated with the plasmid survival time remaining in lungs and brains prior to its degradation. PMID- 22056983 TI - Treatment of osteonecrosis of the femoral head with VEGF165 transgenic bone marrow mesenchymal stem cells in mongrel dogs. AB - We evaluated the efficacy of vascular endothelial growth factor 165 (VEGF(165)) transgenic bone marrow mesenchymal stem cells (BMSCs) for the repair of early stage osteonecrosis of the femoral head (ONFH) in mature mongrel dogs. This animal model was surgically established by femoral neck osteotomy and subsequent repinning. Twenty-seven dogs (54 hips) were divided into 3 equal-sized groups: a pCI-neo-VEGF(165) BMSC group, a pCI-neo BMSC group and a core decompression-alone group. The lipofectamine was used to introduce the VEGF(165) gene into the BMSCs. After core decompression, transgenic and non-transgenic autologous BMSCs were implanted. Therapeutic efficacy, including new bone formation and neovascularization in the femoral head, was examined by computed radiography, single-photon emission computed tomography, histological and histomorphometric analysis and immunofluorescent staining for von Willebrand factor in pathological sections. The femoral osteotomy site healed completely by the 4th week after the osteotomy surgery and regions of histologically evident osteonecrosis were found 12 weeks later. A regular arrangement of trabeculae and obvious bone regeneration were observed in the animals receiving implanted VEGF-transgenic BMSCs. The quantity of newly generated capillaries was significantly increased in the pCI neo-VEGF(165) BMSC group, but there was no significant difference between the pCI neo BMSC group and the core decompression-alone group. These results demonstrated that VEGF(165) transgenic autologous BMSCs enhanced bone reconstruction and blood vessel regeneration in the ONFH model. Compared with non-transgenic BMSCs, this approach could provide advanced benefits in the treatment of ONFH. PMID- 22056984 TI - Condom use and partnership intimacy among drug injectors and their sexual partners in Estonia. AB - OBJECTIVES: Young age coupled with a high HIV prevalence among injection drug users (IDUs) and the prevalence of drug use in Eastern Europe can lead from an HIV epidemic concentrated among IDU to a self-sustained heterosexual HIV epidemic. Our objective was to explore the contexts of the prevention of sexual transmission of HIV among IDUs and their sexual partners and to provide insight into beliefs and behaviours related to condom use. METHODS: The authors undertook in-depth qualitative interviews to explore narratives about experience of preventing sexual transmission of HIV among 27 individuals (15 current IDUs and 12 main sexual partners of IDUs) in Kohtla-Jarve, Estonia. RESULTS: The safe-sex 'norm' was not common and factors that tended to reduce condom use included valuing the relationship above health risks, established gender roles, perceptions that condoms distributed via harm reduction programmes were of low quality and the stigma attached to HIV status disclosure. HIV risk management strategies among participants included consistent condom use and serosorting but were countered by a fatalism that encompassed consciously subjecting oneself to the inevitability of HIV infection in an HIV-discordant sexual partnership. CONCLUSIONS: Qualitative methods can significantly contribute to the prevention of sexual transmission of HIV among and beyond IDUs by improving our understanding of risky behaviours and the reasons for such behaviours that can be incorporated into tailored public health interventions. PMID- 22056985 TI - Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw. AB - Permafrost contains an estimated 1672 Pg carbon (C), an amount roughly equivalent to the total currently contained within land plants and the atmosphere. This reservoir of C is vulnerable to decomposition as rising global temperatures cause the permafrost to thaw. During thaw, trapped organic matter may become more accessible for microbial degradation and result in greenhouse gas emissions. Despite recent advances in the use of molecular tools to study permafrost microbial communities, their response to thaw remains unclear. Here we use deep metagenomic sequencing to determine the impact of thaw on microbial phylogenetic and functional genes, and relate these data to measurements of methane emissions. Metagenomics, the direct sequencing of DNA from the environment, allows the examination of whole biochemical pathways and associated processes, as opposed to individual pieces of the metabolic puzzle. Our metagenome analyses reveal that during transition from a frozen to a thawed state there are rapid shifts in many microbial, phylogenetic and functional gene abundances and pathways. After one week of incubation at 5 degrees C, permafrost metagenomes converge to be more similar to each other than while they are frozen. We find that multiple genes involved in cycling of C and nitrogen shift rapidly during thaw. We also construct the first draft genome from a complex soil metagenome, which corresponds to a novel methanogen. Methane previously accumulated in permafrost is released during thaw and subsequently consumed by methanotrophic bacteria. Together these data point towards the importance of rapid cycling of methane and nitrogen in thawing permafrost. PMID- 22056986 TI - Chromatin-associated RNA interference components contribute to transcriptional regulation in Drosophila. AB - RNA interference (RNAi) pathways have evolved as important modulators of gene expression that operate in the cytoplasm by degrading RNA target molecules through the activity of short (21-30 nucleotide) RNAs. RNAi components have been reported to have a role in the nucleus, as they are involved in epigenetic regulation and heterochromatin formation. However, although RNAi-mediated post transcriptional gene silencing is well documented, the mechanisms of RNAi mediated transcriptional gene silencing and, in particular, the role of RNAi components in chromatin dynamics, especially in animal multicellular organisms, are elusive. Here we show that the key RNAi components Dicer 2 (DCR2) and Argonaute 2 (AGO2) associate with chromatin (with a strong preference for euchromatic, transcriptionally active, loci) and interact with the core transcription machinery. Notably, loss of function of DCR2 or AGO2 showed that transcriptional defects are accompanied by the perturbation of RNA polymerase II positioning on promoters. Furthermore, after heat shock, both Dcr2 and Ago2 null mutations, as well as missense mutations that compromise the RNAi activity, impaired the global dynamics of RNA polymerase II. Finally, the deep sequencing of the AGO2-associated small RNAs (AGO2 RIP-seq) revealed that AGO2 is strongly enriched in small RNAs that encompass the promoter regions and other regions of heat-shock and other genetic loci on both the sense and antisense DNA strands, but with a strong bias for the antisense strand, particularly after heat shock. Taken together, our results show that DCR2 and AGO2 are globally associated with transcriptionally active loci and may have a pivotal role in shaping the transcriptome by controlling the processivity of RNA polymerase II. PMID- 22056987 TI - Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. AB - A formidable challenge in neural repair in the adult central nervous system (CNS) is the long distances that regenerating axons often need to travel in order to reconnect with their targets. Thus, a sustained capacity for axon regeneration is critical for achieving functional restoration. Although deletion of either phosphatase and tensin homologue (PTEN), a negative regulator of mammalian target of rapamycin (mTOR), or suppressor of cytokine signalling 3 (SOCS3), a negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, in adult retinal ganglion cells (RGCs) individually promoted significant optic nerve regeneration, such regrowth tapered off around 2 weeks after the crush injury. Here we show that, remarkably, simultaneous deletion of both PTEN and SOCS3 enables robust and sustained axon regeneration. We further show that PTEN and SOCS3 regulate two independent pathways that act synergistically to promote enhanced axon regeneration. Gene expression analyses suggest that double deletion not only results in the induction of many growth related genes, but also allows RGCs to maintain the expression of a repertoire of genes at the physiological level after injury. Our results reveal concurrent activation of mTOR and STAT3 pathways as key for sustaining long-distance axon regeneration in adult CNS, a crucial step towards functional recovery. PMID- 22056988 TI - Nuclear PKM2 regulates beta-catenin transactivation upon EGFR activation. AB - The embryonic pyruvate kinase M2 (PKM2) isoform is highly expressed in human cancer. In contrast to the established role of PKM2 in aerobic glycolysis or the Warburg effect, its non-metabolic functions remain elusive. Here we demonstrate, in human cancer cells, that epidermal growth factor receptor (EGFR) activation induces translocation of PKM2, but not PKM1, into the nucleus, where K433 of PKM2 binds to c-Src-phosphorylated Y333 of beta-catenin. This interaction is required for both proteins to be recruited to the CCND1 promoter, leading to HDAC3 removal from the promoter, histone H3 acetylation and cyclin D1 expression. PKM2 dependent beta-catenin transactivation is instrumental in EGFR-promoted tumour cell proliferation and brain tumour development. In addition, positive correlations have been identified between c-Src activity, beta-catenin Y333 phosphorylation and PKM2 nuclear accumulation in human glioblastoma specimens. Furthermore, levels of beta-catenin phosphorylation and nuclear PKM2 have been correlated with grades of glioma malignancy and prognosis. These findings reveal that EGF induces beta-catenin transactivation via a mechanism distinct from that induced by Wnt/Wingless and highlight the essential non-metabolic functions of PKM2 in EGFR-promoted beta-catenin transactivation, cell proliferation and tumorigenesis. PMID- 22056989 TI - Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. AB - Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However, the effective use of PSCs for cell therapy has lagged behind. Whereas mouse PSC-derived DA neurons have shown efficacy in models of Parkinson's disease, DA neurons from human PSCs generally show poor in vivo performance. There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor plate precursors are derived from PSCs 11 days after exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signalling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of PSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in Parkinson's disease models using three host species. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson's disease. PMID- 22056991 TI - (75)As NMR study of antiferromagnetic fluctuations in Ba(Fe(1-x)Ru(x))(2)As(2). AB - The evolution of (75)As NMR parameters with composition and temperature was probed in the Ba(Fe(1-x)Ru(x))(2)As(2) system where Fe is replaced by isovalent Ru. While the Ru end member was found to be a conventional Fermi liquid, the composition (x = 0.5) corresponding to the highest T(c) (20 K) in this system shows an upturn in the (75)As [Formula: see text] below about 80 K, evidencing the presence of antiferromagnetic (AFM) fluctuations. These results are similar to those obtained in another system with isovalent substitution, BaFe(2)(As(1 x)P(x))(2) (Nakai et al 2010 Phys. Rev. Lett. 105 107003) and point to a possible role of AFM fluctuations in driving superconductivity. PMID- 22056990 TI - HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. AB - SAMHD1, an analogue of the murine interferon (IFN)-gamma-induced gene Mg11 (ref. 1), has recently been identified as a human immunodeficiency virus-1 (HIV-1) restriction factor that blocks early-stage virus replication in dendritic and other myeloid cells and is the target of the lentiviral protein Vpx, which can relieve HIV-1 restriction. SAMHD1 is also associated with Aicardi-Goutieres syndrome (AGS), an inflammatory encephalopathy characterized by chronic cerebrospinal fluid lymphocytosis and elevated levels of the antiviral cytokine IFN-alpha. The pathology associated with AGS resembles congenital viral infection, such as transplacentally acquired HIV. Here we show that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate. The crystal structure of the catalytic core of SAMHD1 reveals that the protein is dimeric and indicates a molecular basis for dGTP stimulation of catalytic activity against dNTPs. We propose that SAMHD1, which is highly expressed in dendritic cells, restricts HIV-1 replication by hydrolysing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA (cDNA) synthesis. PMID- 22056992 TI - Premotor and occipital theta asymmetries as discriminators of memory- and stimulus-guided tasks. AB - The saccadic paradigm has been used to investigate specific cortical networks involving visuospatial attention. We examined whether asymmetry in theta and beta band differentiates the role of the hemispheres during the execution of two different prosacadic conditions: a fixed condition, where the stimulus was presented at the same location; and a random condition, where the stimulus was unpredictable. Twelve healthy volunteers (3 male; mean age: 26.25) performed the task while their brain activity pattern was recorded using quantitative electroencephalography. We did not find any significant difference for beta, slow and fast-alpha frequencies for the pairs of electrodes analyzed. The results for theta band showed a superiority of the left hemisphere in the frontal region when responding to the random condition on the right, which is related to the planning and selection of responses, and also a greater activation of the right hemisphere during the random condition, in the occipital region, related to the identification and recognition of patterns. These results indicate that asymmetries in the premotor area and the occipital cortex differentiate memory- and stimulus-driven tasks. PMID- 22056993 TI - 5-HT2A receptor antagonist M100907 reduces serotonin synthesis: an autoradiographic study. AB - The effects of the administration of the serotonin (5-HT)(2A) antagonist, M100907, on 5-HT synthesis rates, were evaluated using the alpha-[(14)C]methyl-l tryptophan (alpha-MTrp) autoradiographic method. In the treatment study, M100907 (10mg/kg) was injected intraperitoneally 30 min before the alpha-MTrp injection (30 MUCi over 2 min). A single dose of M100907 caused a significant decrease in the synthesis in the anterior olfactory nucleus, accumbens nucleus, frontal cortex, sensory-motor cortex, cingulate cortex, medial caudate-putamen, dorsal thalamus, substantia nigra, inferior collicus, raphe magnus nucleus, superior olive, and raphe pallidus nucleus. These data suggest that the terminal 5-HT(2A) receptors are involved in the regulation of 5-HT synthesis in the entire brain. Further, 5-HT synthesis is likely regulated by the 5-HT(2A) antagonistic property of M100907 in the cortices, anterior olfactory nucleus, caudate putamen, and nucleus accumbens. PMID- 22056994 TI - Suppression of MIP-2 or IL-8 production by annexins A1 and A4 during coculturing of macrophages with late apoptotic human peripheral blood neutrophils. AB - Annexin A1 (ANXA1) is a well-known anti-inflammatory protein that is expressed on the surface of apoptotic cells. Annexin A4 (ANXA4) is also recruited from the nucleus to the cytoplasm in apoptotic cells, although it is not known whether or not ANXA4 is expressed on the surface of apoptotic cells. In this study, we obtained rabbit anti-human ANXA1 and ANXA4 antibodies, and then examined whether or not ANXA1 and ANXA4 are expressed on the surface of early and late human apoptotic cells. ANXA1 and, to a lesser extent, ANXA4 were detected on late but not early apoptotic HeLa cells, whereas ANXA1 and a small amount of ANXA4 were detected on both early and late apoptotic human neutrophils. We then examined the effects of the anti-human ANXA1 and ANXA4 antibodies on the mouse or human macrophage response to human apoptotic cells. Upon coculturing of mouse or human macrophages with late apoptotic human neutrophils, anti-human ANXA1 antibodies and, to a lesser extent, anti-human ANXA4 antibodies increased MIP-2 or IL-8 production significantly, suggesting that ANXA1 and ANXA4 suppress MIP-2 or IL-8 production by macrophages in response to late apoptotic human neutrophils. PMID- 22056995 TI - Selective binding and fluorescence sensing of diphosphate in H2O via Zn(2+) induced allosteric regulation of the receptor structure. AB - A terpyridine-based receptor featuring two [9]aneN(3) units is able to selectively bind and sense diphosphate over mono- and triphosphate in aqueous solution at pH 7, thanks to the conformational change of its structure induced by Zn(2+) coordination to the polypyridyl moiety. PMID- 22056996 TI - Secondary malignancies in survivors of breast cancer: how to overcome the risk. AB - Secondary radiation-induced cancers (SRIC) are rare but well-documented as long term side effects of radiation in a large population of breast cancer survivors. The estimate of the standardized incidence ratio is 1.2, increasing with time elapsed from irradiation, and influenced by age, genetic and environmental backgrounds of the patient and systemic treatments. The majority of SRIC occurs in or close to high-dose treatment volume in the intermediate dose level. It is a dose- and rate-dependent phenomenon that rarely occurs in tissues with a cumulative dose of <3.5Gy. Careful patient selection, thorough treatment planning and modern radiation equipment can reduce the dose to the surrounding tissues and decrease the incidence of SRIC. PMID- 22056997 TI - Osteolytic expansile lesions in lumbosacral hydatid disease. PMID- 22056998 TI - Hospital and community validation of a screening instrument for detection of neurodisability in Indian children aged 6 months to 2 years. AB - OBJECTIVE: To develop and validate a screening instrument for neurological disorders in children aged 6 months to 2 years in the community. METHODS: A comprehensive parent-administered instrument was developed to screen for hearing, vision, seizures, motor deficits and development in Indian children aged 6-24 months. This was tested for reliability and validated in the hospital setting by comparing with pre-decided gold standards. It was then used in a community survey in a two-phase design in which all screen positives and a random sample of screen negatives were validated. RESULT: The screening instrument had overall sensitivity, specificity and positive predictive values of 95.8, 68.1 and 76.1%, respectively, in the hospital setting. In the field setting, these figures changed to 95.4, 51.8 and 20.6%, respectively. The reasons for this are discussed. CONCLUSION: Community surveys must use a two-phase design to get the true prevalence. A falsely high prevalence will be computed if only a single phase design or hospital validation is used. PMID- 22056999 TI - A stepwise validation of a wearable system for estimating energy expenditure in field-based research. AB - Regular physical activity (PA) is an important contributor to a healthy lifestyle. Currently, standard sensor-based methods to assess PA in field-based research rely on a single accelerometer mounted near the body's center of mass. This paper introduces a wearable system that estimates energy expenditure (EE) based on seven recognized activity types. The system was developed with data from 32 healthy subjects and consists of a chest mounted heart rate belt and two accelerometers attached to a thigh and dominant upper arm. The system was validated with 12 other subjects under restricted lab conditions and simulated free-living conditions against indirect calorimetry, as well as in subjects' habitual environments for 2 weeks against the doubly labeled water method. Our stepwise validation methodology gradually trades reference information from the lab against realistic data from the field. The average accuracy for EE estimation was 88% for restricted lab conditions, 55% for simulated free-living conditions and 87% and 91% for the estimation of average daily EE over the period of 1 and 2 weeks. PMID- 22057000 TI - The oxytocin/vasopressin receptor family has at least five members in the gnathostome lineage, inclucing two distinct V2 subtypes. AB - The vertebrate oxytocin and vasopressin receptors form a family of G-protein coupled receptors (GPCRs) that mediate a large variety of functions, including social behavior and the regulation of blood pressure, water balance and reproduction. In mammals four family members have been identified, three of which respond to vasopressin (VP) named V1A, V1B and V2, and one of which is activated by oxytocin (OT), called the OT receptor. Four receptors have been identified in chicken as well, but these have received different names. Until recently only V1 type receptors have been described in several species of teleost fishes. We have identified family members in several gnathostome genomes and performed phylogenetic analyses to classify OT/VP-receptors across species and determine orthology relationships. Our phylogenetic tree identifies five distinct ancestral gnathostome receptor subtypes in the OT/VP receptor family: V1A, V1B, V2A, V2B and OT receptors. The existence of distinct V2A and V2B receptors has not been previously recognized. We have found these two subtypes in all examined teleost genomes as well as in available frog and lizard genomes and conclude that the V2A type is orthologous to mammalian V2 receptors whereas the V2B-type is orthologous to avian V2 receptors. Some teleost fishes have acquired additional and more recent gene duplicates with up to eight receptor family members. Thus, this analysis reveals an unprecedented complexity in the gnathostome repertoire of OT/VP receptors, opening interesting research avenues regarding functions such as regulation of water balance, reproduction and behavior, particularly in reptiles, amphibians, teleost fishes and cartilaginous fishes. PMID- 22057002 TI - Current progress in the assessment of 'liking' vs. 'wanting' food in human appetite. Comment on '"You say it's liking, i say it's wanting...". On the difficulty of disentangling food reward in man'. AB - Studies that make use of separate measures to capture 'liking' and 'wanting' components of food reward signal a paradigm shift in research on hedonic (over)eating in man. In a recent review, Havermans (2011) highlighted some key methodological and theoretical challenges faced by those working on this issue. Unfortunately, this selective reading of the recent literature in the field presents a skewed picture; but it should not dampen the building momentum. On the other hand the paper is a timely call for researchers to clarify some of the neological confusion that has inevitably been generated along the way. In this response to Havermans (2011), we offer a more robust review of current progress in the assessment of 'liking' vs. 'wanting' food in human appetite. The evidence supports important theoretical and practical implications for a dual-process account of food reward; the developing nature of the research means the majority of these remain tantalisingly unexplored. PMID- 22057003 TI - Sialome analysis of the cephalochordate Branchiostoma belcheri, a key organism for vertebrate evolution. AB - Sialic acid, a common terminal substitution of glycoconjugates, has been so far consistently identified in all vertebrates as well as in a growing number of bacterial species. It is assumed to be widely distributed among animal species of the deuterostome phylum, based on its identification in few echinoderm and all vertebrate species. However, whole sections of deuterostome, especially those intermediate species between invertebrates and vertebrates including cephalochordates, urochordates and hemichordates, are still unexplored in term of sialylation capacities. The discovery of functional sialic acid machinery in some of these species may shed new light onto the evolution of glycosylation capacities in deuterostome lineage. In a first approach, we investigated the sialylation pattern of a cephalocordate species, Branchiostoma belcheri, which occupies a strategic phylogenetic position to understand the transition of invertebrates toward vertebrates. Structural analysis of B. belcheri glycoconjugates established that this organism synthesizes large quantities of various sialic acids, some of which present rare or novel structures such as methylated sialic acids. These sialic acids were shown to be mainly associated with mono- and disialylated core 1-type O-glycans. Moreover, screening of the animal organs revealed the existence of exquisite tissue specificity in the distribution of sialic acids. Description of sialylation profiles was then correlated with the expression patterns of key enzymes involved in the biosynthesis of major forms of sialic acids, which provides the first complete overview of the sialylation patterns in cephalochordates. PMID- 22057004 TI - Mycoplasma genitalium: a comparative genomics study of metabolic pathways for the identification of drug and vaccine targets. AB - Increasing emergence of antibiotic-resistant pathogenic microorganisms is one of the biggest challenges for biomedical research and drug development. Traditional drug discovery methods are time-consuming, expensive and often yield few drug targets. In contrast, advances in complete genome sequencing, bioinformatics and cheminformatics represent an attractive alternative approach to identify drug targets worthy of experimental follow-up. Mycoplasma genitalium is a human parasitic pathogen that is associated with several sexually transmitted diseases. Recently, emergence of treatment-resistant isolates has been reported, which raises serious concern and a need for identification of additional drug targets. In the present study, a systematic workflow consisting of comparative genomics, metabolic pathways analysis and additional drug prioritizing parameters was defined for the identification of novel drug and vaccine targets that are essential for M. genitalium, but absent in its human host. In silico analyses and manual mining identified 79 proteins of M. genitalium, which showed no similarity to human proteins. Among these, 67 proteins were identified as non-homologous essential proteins that could serve as potential drug and vaccine targets. Subcellular localization, molecular weight, and three-dimensional structural characteristics that could facilitate filtering of attractive drug targets were also calculated for the non-homologous essential proteins. Enzymes from thiamine biosynthesis, protein biosynthesis, and folate biosynthesis were identified as attractive candidates for drug development. Furthermore, druggability of each of the identified drug targets was also evaluated by the DrugBank database. Results from this study could facilitate selection of M. genitalium proteins for entry into drug design and vaccine production pipelines. PMID- 22057005 TI - Unspecific ligand binding yielding stable colloidal ITO-nanoparticle dispersions. AB - Long-term stable ITO-nanoparticle dispersions are obtained using primary unbranched alkylamines with different chain lengths (C(3)-C(12)). The particles are stable despite weak interactions between the stabiliser and particle surface, which were qualitatively studied by (1)H-NMR spectroscopy and quantitatively by isothermal titration calorimetry (ITC). PMID- 22057006 TI - Atraumatic osteonecrosis of the distal radius and ulna: case series and review. AB - PURPOSE: Atraumatic multifocal osteonecrosis is defined as the occurrence of atraumatic osteonecrosis in 3 or more anatomic locations, and it is rare. We identified 6 patients with osteonecrotic lesions in the distal ulna, radius, or both. The purposes of this study were to describe the clinical manifestations of atraumatic multifocal osteonecrosis affecting these bones, to identify risk factors for developing the disease in these locations, and to evaluate the success of treatment by percutaneous drilling. METHODS: A total of 10 wrists in 6 women with a mean age of 41 years had symptomatic osteonecrosis. Patients were treated by percutaneous drilling after they had failed nonoperative modalities. Clinical evaluation included preoperative and postoperative Michigan Hand Questionnaire scores plain radiographs, and MRI evaluations were performed to characterize the disease. The incidence of risk factors was recorded. RESULTS: There was disease occurrence in the radius in all 10 wrists and in the ulnas of 4 wrists. All patients presented with symptomatic osteonecrosis of the large joints (primarily knee or hip), presumably secondary to corticosteroid use. These patients later developed symptomatic pain in the distal ulna, radius, or both that impaired daily activities. Other risk factors included alcohol or tobacco use, blood dyscrasias, and systemic lupus erythematosus. Treatment consisted of percutaneous drilling of the distal radius (and ulna when affected). One patient required additional bilateral drillings and had further improvement in her Michigan Hand Questionnaire scores. At a mean follow up of 35 months, there was no disease progression as evident radiographically. CONCLUSIONS: The distal radius and ulna are rare sites of osteonecrosis associated with multifocal disease. The clinical presentation and risk factors are similar to osteonecrosis in the large joints. Magnetic resonance imaging identifies necrotic lesions. The present study suggests that disease in these sites can be safely and effectively treated with percutaneous drilling. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 22057007 TI - Management and outcome of appendicitis among octogenarians in an English hospital over a five year period. AB - INTRODUCTION: There is a different perspective on diagnosis and management of common surgical problems in elderly patients. This study aimed to analyse the management of acute appendicitis in octogenarians. METHODS: A retrospective study investigated all appendicectomies over five years. Patient records were studied for presenting features, pre-operative imaging, pre-operative ASA grade, site of incision, post-operative complications and length of inpatient stay. RESULTS: Presenting symptoms included lower abdominal pain (n = 31, 93.9%), anorexia (n = 19, 57.6%), nausea and vomiting (n = 15, 45.5%) and shifting pain (n = 10, 30.3%). Twenty patients had right iliac fossa pain (60.6%) and seven had pyrexia (21.2%). The commonest co-morbidity was cardiac (n = 19; 58%). The average time from admission to theatre was greater in octogenarian patients (1.24 +/- 0.90 days) than other patients (0.64 +/- 0.71 days), as was the average length of stay at 11 +/- 2.6 days compared with 4.3 +/- 3.1 days. The majority of octogenarian patients received a Lanz incision (48.3%), with others receiving laparotomy (24.1%), lower midline (13.8%), gridiron (13.8%), and right paramedian (3.4%). Complications were more common in the octogenarian patients (63.6%) than other patients (22.55%). The most common complications in the octogenarian population were post-operative ileus (n = 7; 21%), wound infection (n = 5; 15.2%) and pneumonia (n = 5; 15.2%). CONCLUSION: Appendicitis in the elderly can result in significant morbidity due to the atypical presentation causing an unnecessary delay in treatment. If indicated, age should not be a contraindication for an appendicectomy. The increased likelihood for these patients to have a post operative complication should be at the forefront of their care. PMID- 22057008 TI - Delivering quality of care while managing the interests of all stakeholders. AB - National healthcare systems worldwide face growing challenges to reconcile interests of patients for high-quality medical care and of payers for sustainable and affordable funding. Advances in the provision of renal replacement therapy can only be made by developing and implementing appropriate sophisticated and state-of-the-art business models that include reimbursement schemes for comprehensive care packages. Such business models must succeed in integrating and reconciling the interests of all stakeholders. NephroCare as dialysis provider has adopted and tailored recognized management techniques, i.e. Balanced Scorecard and Kaizen, to achieve these goals. Success of the complete business model package is tangible - strategies initiated to improve treatment quality even at the cost of providers have been translated into win-win scenarios for the complete stakeholder community. Room for improvement exists: the possibility to extend the portfolio of service offerings within the comprehensive care frame, as well as the challenge for achieving a balance between the stability of targets while keeping these up to date concerning new insights. PMID- 22057009 TI - Reconstruction and analysis of human heart-specific metabolic network based on transcriptome and proteome data. AB - The availability and utility of genome-scale metabolic networks have exploded with modern genome-sequencing capabilities. However, these generic models overlooked actual physiological states of the tissues and included all the reactions implied by the genome annotations. To address this problem, we reconstructed a human heart-specific metabolic network based on transcriptome and proteome data. The resulting model consists of 2803 reactions and 1880 metabolites, which correspond to 1721 active enzymes in human heart. Using the model, we detected 24 epistatic interactions in human heart, which are useful in understanding both the structure and function of cardiovascular systems. In addition, a set of 776 potential biomarkers for cardiovascular disease (CVD) has been successfully explored, whose concentration is predicted to be either elevated or reduced because of 278 possible dysfunctional cardiovascular associated genes. The model could also be applied in predicting selective drug targets for eight subtypes of CVD. The human heart-specific model provides valuable information for the studies of cardiac activity and development of CVD. PMID- 22057010 TI - Activation of mitochondrial MU-calpain increases AIF cleavage in cardiac mitochondria during ischemia-reperfusion. AB - Ubiquitous calpains (calpain I and II) are generally recognized as cytosolic proteins. Recently, mitochondrial localized calpain I (MU-calpain) has been identified. Activation of mito-MU-calpain cleaves apoptosis inducing factor (AIF), a flavoprotein located within the mitochondrial intermembrane space, in liver mitochondria, but not in brain mitochondria. We first tested if activation of mito-MU-calpain cleaves AIF in isolated heart mitochondria. A decrease in AIF content within mitochondria increases cardiac injury during ischemia-reperfusion by augmenting oxidative stress. We hypothesize that the activation of mito-MU calpain by calcium overload during ischemia-reperfusion results in decreased AIF content within mitochondria by cleaving AIF. The MU-calpain was present within mouse heart mitochondria, mostly in the intermembrane space. Exogenous calcium treatment induced a calpain-dependent decrease of mitochondrial AIF content in isolated mouse heart mitochondria. This process was blocked by a calpain inhibitor (MDL-28170). The Mitochondrial MU-calpain activity was increased by 160 +/- 15% during ischemia-reperfusion compared to time control. In contrast, the mitochondrial AIF content was decreased by 52 +/- 7% during reperfusion vs. time control in the buffer perfused mouse heart. Inhibition of mito-MU-calpain using MDL-28170 decreased cardiac injury by preserving AIF content within mitochondria during ischemia-reperfusion. Thus, activation of mito-MU-calpain is required to release AIF from cardiac mitochondria. Inhibition of calpains using MDL-28170 decreases cardiac injury by inhibiting both cytosolic calpains and mito-MU calpain during ischemia-reperfusion. PMID- 22057011 TI - The size and phospholipid composition of lipid droplets can influence their proteome. AB - The proteomic makeup of lipid droplets (LDs) is believed to regulate the function of LDs, which are now recognized as important cellular organelles that are associated with many human metabolic disorders. However, factors that help determine LD proteome remain to be identified and characterized. Here we analyzed the phospholipid and protein composition of LDs isolated from wild type (WT) yeast cells, and also from fld1Delta, cds1, and ino2Delta mutant cells which produce 'supersized' LDs. LDs of fld1Delta and WT cells exhibited similar phospholipid profiles, whereas LDs of cds1 and ino2Delta strains had a higher (cds1) or lower (ino2Delta) percentage of phosphatidylcholine than those of WT, respectively. Unexpectedly, the presence of most known LD resident proteins was greatly reduced in the LD fraction isolated from cds1 and ino2Delta, including neutral lipid hydrolases. Consistent with this result, mobilization of neutral lipids was seriously impaired in these two strains. Contrary to the reduction of LD resident proteins, the Hsp90 family molecular chaperones, Hsc82 and Hsp82, were greatly increased in the LD fractions of cds1 and ino2Delta strains without changes at the level of expression. These data demonstrate the impact of LD phopholipids and size on the makeup of LD proteome. PMID- 22057012 TI - The global distribution and evolution of deoxyribonucleoside kinases in bacteria. AB - Deoxyribonucleoside kinases (dNKs) are important to DNA metabolism, especially in environments where nucleosides are freely available to be absorbed and used for the salvage pathway. Little has previously been known about the complement of dNKs in different bacterial genomes. However, it was believed that Gram-negative bacteria had a single dNK, while Gram-positive bacteria possessed several. An analysis of 992 fully sequenced bacterial genomes, including both Gram-positive and Gram-negative organisms, was conducted to investigate the phylogenetic relationship of all TK1-like and non-TK1-like dNKs. It was illustrated that both gene families evolved through a number of duplications and horizontal gene transfers, leading to the presence of multiple dNKs in different types of bacteria. The findings of this study provide a backbone for further studies into the evolution of the interplay between the de novo and salvage pathways in DNA synthesis with respect to environmental availability of deoxyribonucleosides and metabolic processes generating the provisions of different dNTPs. PMID- 22057013 TI - METCAM/MUC18 augments migration, invasion, and tumorigenicity of human breast cancer SK-BR-3 cells. AB - Previous research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as a promoter or a suppressor in the development of human breast cancer by MCF7, MDA-MB-231, and MDA-MB-468. To resolve these conflicting results we have investigated the role of this CAM in the progression of the three aforementioned cell lines plus one additional human breast cancer cell line, SK-BR-3. We transfected the SK-BR-3 cells with human METCAM/MUC18 cDNA to obtain G418-resistant clones, which expressed different levels of the protein and which were used to test the effect of human METCAM/MUC18 expression on in vitro motility, invasiveness, anchorage-independent colony formation in soft agar, disorganized growth in a 3D basement membrane culture assay, and in vivo tumorigenesis in athymic nude mice. Enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, and anchorage independent colony formation of SK-BR-3 cells and favored disorganized growth of the cells in 3D basement membrane culture. Enforced expression also increased tumorigenicity and final tumor weights of SK-BR-3 clones/cells after subcutaneous injection of the cells under the left third nipple of female athymic nude mice. To understand the mechanisms, we also determined the expression of several downstream key effectors in the tumors. Tumor cells from METCAM/MUC18 expressing clones exhibited elevated expression of an anti-apoptotic and survival index (Bcl2), an aerobic glycolysis index (LDH-A), and pro-angiogenesis indexes (VEGF and VAGFR2). We concluded that human METCAM/MUC18 promotes the development of breast cancer cells by increasing an anti-apoptosis and survival pathway and augmenting aerobic glycolysis and angiogenesis. PMID- 22057014 TI - Tetrode recordings in the cerebellar cortex. AB - Multi-unit recordings with tetrodes have been used in brain studies for many years, but surprisingly, scarcely in the cerebellum. The cerebellum is subdivided in multiple small functional zones. Understanding the proper features of the cerebellar computations requires a characterization of neuronal activity within each area. By allowing simultaneous recordings of neighboring cells, tetrodes provide a helpful technique to study the dynamics of the cerebellar local networks. Here, we discuss experimental configurations to optimize such recordings and demonstrate their use in the different layers of the cerebellar cortex. We show that tetrodes can also be used to perform simultaneous recordings from neighboring units in freely moving rats using a custom-made drive, thus permitting studies of cerebellar network dynamics in a large variety of behavioral conditions. PMID- 22057015 TI - The association of depression, risky sexual behaviours and herpes simplex virus type 2 in adults in NHANES, 2005-2008. AB - OBJECTIVES: Depression has been linked to risky sexual behaviours in adolescents, but there is little research among adults. The goal of this analysis was to examine the associations between current depression and self-reported risky sexual behaviours in a nationally representative sample of US adults aged 20-59 years. The authors also examined the association between depression and infection with herpes simplex virus type 2 (HSV-2), a biological marker of risky sexual behaviours. METHODS: The authors used data from the 2005-2008 National Health and Nutrition Examination Surveys. Current depression was measured by the Patient Health Questionnaire-9. Antibodies to HSV-2 were tested using the enzymatic immunodot assay. The authors used logistic regression to examine the associations controlling for socio-demographic variables. RESULTS: Among 5273 adults aged 20 59 years, 7% had depression, 36% reported 10 or more lifetime sex partners, 15% had two or more past-year sex partners and 13% had first sex before 15 years of age. Persons with each of the risky sexual behaviours were more likely to have depression than those without. In stratified analyses, risky sexual behaviours were associated with depression in women but not in men. Among 3940 adults aged 20-49 years, 19% had HSV-2 infection. Persons with HSV-2 infection were more likely to have depression (OR 2.1, 95% CI 1.5 to 2.9). CONCLUSIONS: Risky sexual behaviour is related to current depression in adult women. Healthcare providers should be aware of this association and its potential implications in order to deliver better care for patients with depression or sexually transmitted infections. PMID- 22057016 TI - Macroscopic analysis of human masseter compartments assessed by magnetic resonance imaging. AB - The human masseter is divided into compartments by aponeuroses. So far, the qualitative and quantitative features of these compartments and their aponeuroses have been scarcely investigated. This study investigated the three-dimensional compartmentalization of the masseter muscle and tested the hypothesis that aponeurosis content varies systematically across different masseter subportions as well as between genders. The right masseter of 14 healthy participants was scanned by magnetic resonance, and the outlines of muscle and aponeuroses were segmented and rendered in three dimensions by AMIRA software. The internal architecture of the masseter muscle varied markedly across individuals, with respect to the number, shape and location of the compartments delimited by aponeuroses. Aponeuroses were widely represented inside the masseter, amounting to 7.1 +/- 2.1% of its volume. The aponeurosis content varied systematically across masseter subvolumes and did not differ between genders after adjusting for body height and weight. PMID- 22057017 TI - Evidence for the differential co-localization of neurokinin-1 receptors with 5-HT receptor subtypes in rat forebrain. AB - Studies suggest that like selective 5-hydroxytryptamine (5-HT; serotonin) reuptake inhibitors, antagonists at neurokinin-1 receptors (NK(1)Rs) may have antidepressant and anxiolytic properties. NK(1)Rs are present in 5-HT innervated forebrain regions which may provide a common point of interaction between these two transmitter systems. This study aimed to investigate for cellular co localization between NK(1)Rs and 5-HT receptor subtypes in mood-related brain regions in the rat forebrain. With experiments using fluorescence immunocytochemistry, double-labelling methods demonstrated a high degree of co localization between NK(1)Rs and 5-HT(1A) receptors in most regions examined. Co localization was highest in the medial septum (88% NK(1)R expressing cells were 5 HT(1A) receptor-positive) and hippocampal regions (e.g. dentate gyrus, 65%), followed by the lateral/basolateral amygdala (35%) and medial prefrontal cortex (31%). In contrast, co-localization between NK(1)Rs and 5-HT(2A) receptors was infrequent (< 8%) in most areas examined except for the hippocampus (e.g. CA3, 43%). Overall co-localization between NK(1)Rs and 5-HT(1A) receptors was much greater than that between NK(1)Rs and 5-HT(2A) receptors. Thus, these experiments demonstrate a high degree of co-localization between NK(1)Rs and 5-HT(1A) receptors in cortical and limbic regions of the rat forebrain. These findings suggest a novel site of interaction between NK(1)R antagonists and the 5-HT system. PMID- 22057018 TI - EEG spectral power density profiles during NREM sleep for gaboxadol and zolpidem in patients with primary insomnia. AB - There is significant interest in the functional significance and the therapeutic value of slow-wave sleep (SWS)-enhancing drugs. A prerequisite for studies of the functional differences is characterization of the electroencephalography (EEG) spectra following treatment in relevant patients. We evaluate for the first time gaboxadol and zolpidem treatments in insomniac patients using power spectra analysis. We carried out two randomized, double-blind, crossover studies. Study 1, 38 patients received gaboxadol 10 mg and 20 mg and zolpidem 10 mg; study 2, 23 patients received gaboxadol 5 mg and 15 mg. Treatments were administered during two nights and compared with placebo. Gaboxadol 10, 15 and 20 mg enhanced slow wave activity (SWA) and theta power. In 1 Hz bins gaboxadol 10 and 20 mg enhanced power up to 9 Hz. In study 2, 15 mg gaboxadol showed a similar effect pattern. Zolpidem suppressed theta and alpha power, and increased sigma power, with no effect on SWA. In the 1 Hz bins zolpidem suppressed power between 5-10 Hz. Gaboxadol dose-dependently increased SWA and theta power in insomniac patients. In contrast, zolpidem did not affect SWA, reduced theta and alpha activity and enhanced sigma power. EEG spectral power differences may be consequences of the different mechanisms of action for zolpidem and the SWS-enhancing agent, gaboxadol. PMID- 22057019 TI - Antipsychotic drugs and extrapyramidal side effects in first episode psychosis: a systematic review of head-head comparisons. AB - This systematic review aimed to determine whether the risk of extrapyramidal side effects (EPS) differed between antipsychotic drugs used in first episode psychosis (FEP). We identified 11 RCTs comparing two or more antipsychotics in FEP and reporting on EPS. All trials assessed one or more second generation antipsychotics (SGAs), one assessed chlorpromazine, one zuclopenthixol and seven trials assessed haloperidol. Assessment and reporting of EPS varied. Compared with one or more SGA comparators, haloperidol was associated with significantly higher rates/severity of parkinsonism (seven trials) and akathisia (six trials) and greater use of anticholinergics (five trials) and beta-blockers (two trials). Two trials with low-dose haloperidol (<= 4 mg) showed significantly worse EPS outcomes versus a SGA. Two of four long-term haloperidol trials (>= 1 year) found a higher dyskinesia-risk with haloperidol versus olanzapine and risperidone respectively; the remaining two trials found no difference (various SGA comparators). There was an EPS advantage for clozapine versus chlorpromazine (one trial) and risperidone versus zuclopenthixol (one trial). There was little evidence of EPS-differences between SGAs, possibly reflecting use of low doses. We conclude that SGAs offer an EPS advantage over FGAs in FEP though the evidence largely relates to comparisons with haloperidol. Standardized assessment and reporting of EPS would assist future research. PMID- 22057020 TI - Spontaneous epigenetic variation in the Arabidopsis thaliana methylome. AB - Heritable epigenetic polymorphisms, such as differential cytosine methylation, can underlie phenotypic variation. Moreover, wild strains of the plant Arabidopsis thaliana differ in many epialleles, and these can influence the expression of nearby genes. However, to understand their role in evolution, it is imperative to ascertain the emergence rate and stability of epialleles, including those that are not due to structural variation. We have compared genome-wide DNA methylation among 10 A. thaliana lines, derived 30 generations ago from a common ancestor. Epimutations at individual positions were easily detected, and close to 30,000 cytosines in each strain were differentially methylated. In contrast, larger regions of contiguous methylation were much more stable, and the frequency of changes was in the same low range as that of DNA mutations. Like individual positions, the same regions were often affected by differential methylation in independent lines, with evidence for recurrent cycles of forward and reverse mutations. Transposable elements and short interfering RNAs have been causally linked to DNA methylation. In agreement, differentially methylated sites were farther from transposable elements and showed less association with short interfering RNA expression than invariant positions. The biased distribution and frequent reversion of epimutations have important implications for the potential contribution of sequence-independent epialleles to plant evolution. PMID- 22057021 TI - Thermoelectric power of RAgSb(2) (R = Y, La, Ce, and Dy) in zero and applied magnetic fields. AB - We report the experimental results of measurements of the thermoelectric power on the ternary intermetallic compounds RAgSb(2) (R = Y, La, Ce, and Dy) over the temperature range from 2 to 300 K and in magnetic fields up to 140 kOe. In this work, we present the thermoelectric transport properties of four materials from the same family with different ground states: a non-moment bearing paramagnetic metallic system (YAgSb(2)), a non-moment bearing charge density wave system (LaAgSb(2)), a local moment bearing compound with XY-like antiferromagnetic order in the tetragonal basal plane as well as readily accessible metamagnetism (DyAgSb(2)), and a Kondo lattice system with ferromagnetic order below T(C) = 9.7 K (CeAgSb(2)). The thermoelectric power data from these materials exhibit complex temperature and magnetic field dependences, which are associated with modification of the electronic density of states and changes in magnetic scattering. At low temperatures, quantum oscillations in the thermoelectric power are also observed. These oscillations are associated with the Landau quantization of electronic energy in an applied magnetic field. PMID- 22057022 TI - A decade of clinical colorectal cancer. PMID- 22057023 TI - Synthesis of transparent vertically aligned TiO2 nanotubes on a few-layer graphene (FLG) film. AB - Novel transparent 1D-TiO(2)/few-layer graphene electrodes are realised by the anodic growth of vertically aligned TiO(2) nano-tubes on a few-layer graphene film coated on a glass substrate. PMID- 22057024 TI - Selective impairment of optic flow perception in amnestic mild cognitive impairment: evidence from event-related potentials. AB - Alzheimer's disease (AD) patients have visuospatial deficits due to parietal dorsal stream dysfunction. Two distinct dorsal flows have been proposed: the inferior parietal (ventro-dorsal (v-d)) and superior parietal (dorso-dorsal (d d)) streams. We aimed to elucidate how the two dorsal streams are altered in patients with amnestic mild cognitive impairment (aMCI) and AD. Thus, the psychophysical threshold measurements and visual event-related potentials (ERPs) were recorded in patients with aMCI and AD, and in healthy old and young adults. The visual stimuli included radial optic flow (OF) derived from the v-d stream and horizontal (HO) motion conveyed from the d-d stream. The motion thresholds between aMCI patients and old adults were comparable. However, AD patients showed significantly higher motion thresholds for both stimuli compared with other groups. In lower-level ERPs, there were no significant differences in P1 (100 ms) and N1 (130 ms) for both stimuli among the groups. For higher-level ERPs, aMCI patients showed the prolonged latency of OF-specific P200 (v-d origin) and comparable latency of motion-related N170 (V5/MT origin) for both stimuli compared with old adults. In AD patients, both N170 and P200 latencies were significantly prolonged compared with other groups. P200 latency was closely correlated with the Mini-Mental State Examination score. These findings indicate that the v-d function related to OF perception is selectively impaired in aMCI, whereas AD has impairment of the distributed higher-level dorsal stream. Therefore, OF-specific P200 can be useful for detecting early functional changes of the brain in aMCI. PMID- 22057025 TI - Variants in CYP17 and CYP19 cytochrome P450 genes are associated with onset of Alzheimer's disease in women with down syndrome. AB - CYP17 and CYP19 are involved in the peripheral synthesis of estrogens, and polymorphisms in CYP17 and CYP19 have been associated with increased risk of estrogen-related disorders. Women with Down syndrome (DS) have early onset and high risk for Alzheimer's disease (AD). We conducted a prospective community based cohort study to examine the relationship between SNPs in CYP17 and CYP19 and cumulative incidence of AD, hormone levels and sex hormone binding globulin in women with DS. Two hundred and thirty-five women with DS, 31 to 67 years of age and nondemented at initial examination, were assessed for cognitive and functional abilities, behavioral/psychiatric conditions, and health status at 14 20 month intervals over five assessment cycles. We genotyped these individuals for single-nucleotide polymorphisms (SNPs) in CYP17 and CYP19. Four SNPs in CYP17 were associated with a two and one half-fold increased risk of AD, independent of APOE genotype. Four SNPs in CYP19 were associated with a two-fold increased risk of AD, although three were significant only in those without an APOE epsilon4 allele. Further, carrying high risk alleles in both CYP17 and CYP19 was associated with an almost four-fold increased risk of AD (OR = 3.8, 95% CI, 1.6 9.5) and elevated sex hormone binding globulin in postmenopausal women. The main effect of the CYP17 and CYP19 variants was to decrease the age at onset. These findings suggest that genes contributing to estrogen bioavailability influence risk of AD in women with DS. PMID- 22057026 TI - Obesity, cognitive functioning and dementia: back to the future. AB - The conditions of chronic obesity and overweight status are risk factors for lower cognitive performance, cognitive decline, cognitive deficit, and dementia. But lower cognitive performance early in life itself may be a risk factor for an increase in body weight over time. With this in mind, we review important papers in the literature that advance our knowledge of relations between weight and cognitive functioning, with an emphasis on papers that illustrate methodological and theoretical issues of importance. We describe the evolution in research on weight and cognition with respect to two major features: (a) the move backward in time from the diagnosis of dementia to the pre-clinical period of dementia in order to better identify risk factors; and (b) the evolution of studies from an earlier emphasis on obesity-related cardiovascular risk factors as major mediators of relations between obesity and cognition to a more recent emphasis on metabolic variables, lifestyle variables, genotype, and other mechanisms that explain relations among weight change, obesity, and cognition. We conclude that: 1) a complete understanding of the causal links between weight and cognitive functioning requires a lifespan perspective; 2) practically speaking, lifespan research may need to amalgamate and integrate research at different segments of the lifespan until such time that we can include the entire life cycle within a single study of weight and cognition; and 3) we need more studies that examine reciprocal relations between weight and cognition, especially early in life. PMID- 22057027 TI - The isoform-specific pathological effects of apoE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol. AB - Apolipoprotein E4 (apoE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD). Epidemiological studies revealed that consumption of docosahexaenoic acid (DHA: 22 : 6 (omega3)), a major brain polyunsaturated fatty acid, is protective for AD and that elevated cholesterol levels are an AD risk factor. We presently investigated the extent to which the pathological effects of apoE4 in vivo can be prevented by consuming fish oil (DHA) or can be modified by cholesterol. Accordingly, apoE3- and apoE4-targeted replacement mice were subjected, following weaning, to a fish oil diet enriched in DHA and to a cholesterol-containing diet under regular and enriched environments. Cholesterol metabolism in the hippocampus and the corresponding phospholipid and fatty acid levels were affected by fish oil (DHA) and cholesterol diets and by environmental stimulation. Importantly, cholesterol metabolism and the fatty acid levels were not affected by apoE4. The phospholipid levels were, however, affected by apoE4. This effect was most pronounced in the cholesterol-fed mice and was abolished by the fish oil (DHA) diet. ApoE4 elevated hippocampal intraneuronal amyloid-beta levels under regular conditions and lowered them following environmental stimulation, relative to those of the apoE3 mice. ApoE4 also elevated the levels of the presynaptic transporters Vglut and Vgat, and decreased behavioral performance in an object recognition test. Importantly, all of these apoE4 phenotypes were abolished by the fish oil (DHA) diet, whereas the cholesterol diet modified them. These findings suggest that a fish oil (DHA) diet could be used to attenuate the effects of apoE4 in AD. PMID- 22057028 TI - The dying of the light: mitochondrial failure in Alzheimer's disease. AB - Impaired brain energy production, reflected by reduced cortical glucose metabolism seen on 2-FDG PET scans, has emerged as a robust biomarker of mild cognitive impairment (MCI). Progression from MCI to Alzheimer's disease (AD) shows further decline of cortical 2-FDG uptake, implying worsening bioenergetics. We characterized respiration, respiratory protein levels, and gene expressions for mitochondrial DNA (mtDNA), mitochondrial biogenesis, and antioxidative signaling in preparations from postmortem AD and control frontal cortex. Mitochondrial respiration was maintained in frozen brain mitochondria and reduced by approximately two-thirds in AD due to loss of mitochondrial mass. Levels of most respiratory proteins were preserved, but expressions of gene families for mtDNA, mitobiogenesis, and mitochondrial/cytosolic antioxidant enzymes were reduced in AD cortex. None of these changes in AD were related to elevated levels of amyoid-beta1-42 peptide. For unclear reasons, mitochondrial biogenesis is suppressed in AD frontal cortex, leading to reduced mitochondrial mass and impaired mitochondrial respiratory capacity. Downregulation of antioxidant proteins further threatens neuronal function. Altering progression of AD appears to require both correction of impaired mitobiogenesis and restoration of antioxidant protection. PMID- 22057029 TI - Pain perception, pain drug therapy and health status in patients with Parkinson's disease. AB - BACKGROUND: Parkinson's disease (PD) is traditionally characterized as a movement disorder; however, sensory perception problems including pain syndromes are also frequent. We performed a survey to analyze the relations between health status, pain perception and gender in 4,086 PD patients. Moreover, the participants should tick whether they took pain medications or not. SUBJECTS AND METHODS: The questionnaire included the EQ-5D and visual analogue scales (VAS) on pain, which asked for mean (VAS A), most (VAS B), and minimal (VAS C) intensity of pain during an interval of 4 weeks prior to the completion of the survey. RESULTS: PD patients were divided into three groups according to their EQ-5D total score (I: <8; II: 8-9; III: 10-15). An impairment of health status occurred in relation to the increase in pain syndromes in PD patients. There was a significant increase in VAS scores in relation to the EQ-5D group membership. Female patients reported more on pain and more frequently received a pain drug treatment than male patients. Significant associations were found between the VAS and the EQ-5D scores, and the correlation coefficients were higher in men than in women. CONCLUSIONS: Pain is associated with the health status of PD patients and worsens it. More female than male PD patients have to deal with handling of pain and pain drug treatment. PMID- 22057030 TI - Frustrated magnetism in the S = 1 kagome lattice BaNi3(OH)2(VO4)2. AB - Frustrated magnets with integer spin are predicted to have exotic physical properties including spin nematicity, yet few are known to exist. We report a new, frustrated S = 1 magnet, BaNi(3)(OH)(2)(VO(4))(2), which is the structural analogue of the mineral vesignieite. Magnetic frustration arises from a competition between ferromagnetic and antiferromagnetic ordering leading to a glassy transition at 19 K. PMID- 22057031 TI - The role of the androgen receptor in anabolic androgenic steroid-induced aggressive behavior in C57BL/6J and Tfm mice. AB - Humans self-administer anabolic androgenic steroids (AAS) at superphysiological doses for the purpose of building muscle mass and enhancing physique whereas considerably lower doses of AAS are prescribed in the clinic to treat a variety of disorders. A number of studies have demonstrated that individual AAS influence aggressive behavior in rats and mice, but few studies have examined the aggression-enhancing effects of combinations of AAS. Using the resident-intruder paradigm, Experiment 1 determined whether a cocktail of commonly abused AAS increased aggressive behavior in gonadally-intact male C57BL/6J mice and examined whether the androgen receptor (AR) was involved. Mice given either AAS cocktail or the cocktail and the AR antagonist, flutamide, for 6 weeks were subject to three weekly tests in which the percentage of mice that fought, the latency to initiate an aggressive event and the number of aggressive events per 5-min-fight session were recorded. In C57BL/6J mice, 6 weeks of AAS administration increased the likelihood of fighting, however, within the subset of mice that engaged in aggression, AAS did not specifically modulate the latency to fight or the number of aggressive events per fight. In addition, co-administration of flutamide only slightly altered the likelihood that mice given AAS will initiate a fight. Experiment 2 examined the aggression-promoting effects of AAS in gonadally-intact adult testicular feminization mutant (Tfm) mice, which are deficient in functional ARs. Overall, fewer Tfm mice compared to C57BL/6J mice fought in both drug conditions (vehicle or AAS). Taken together, these data suggest that given the presence of AR during development, AAS enhance adult male aggression in C57BL/6J mice through AR-independent and AR-dependent pathways. In contrast, in adult Tfm mice, the likelihood of AAS-enhanced aggression in adulthood is significantly reduced. PMID- 22057032 TI - Detection of multiple cytokines in the urine of patients with focal necrotising glomerulonephritis may predict short and long term outcome of renal function. AB - BACKGROUND: Detection of urinary cytokines in pauci-immune focal segmental necrotizing glomerulonephritis (FSNGN) may provide valuable information about disease pathogenesis and prognosis. METHODS: Epidermal growth factor (EGF), transforming growth factor (TGF-beta1) and vascular endothelial growth factor (VEGF) were measured by ELISA, and Interleukins, monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein (MIP1beta) by a multiplex cytokine assay, in 38 patients with FSNGN. Their levels were correlated with severity of histological findings and renal function outcome in short and long term. RESULTS: The percentage of crescents in renal biopsy had positive correlation with TGF beta1 (p=0.004) and IL-15 urinary excretion (p=0.01), and negative correlation with EGF (p=0.01). Increased urinary excretion of IL-6, IL-15, VEGF and MIP-1beta was associated with poor renal function outcome, but increased levels of EGF, IL 2 and IL-9 predicted a favourable prognosis. In multiple regression analysis IL-6 and VEGF urinary levels were independent predictors of no-response at the acute phase (p=0.001 and p<0.0001, respectively), while, IL-6 was the only factor (p=0.03) predicted worse outcome at the end of follow-up (39.4+/-45 months). CONCLUSION: Increased urinary excretion of IL-6, IL-15, VEGF, TGF-beta1, MCP-1 and MIP-1beta and reduced EGF, IL-2, IL-9 may be associated with histological damage and influence response to treatment in pauci-immune FSNGN. PMID- 22057034 TI - Developmental stage-specific changes in immunological biomarkers in male C3H/HeN mice after early life toluene exposure. AB - We investigated the effects of low-level toluene exposure on immunological biomarkers during different developmental stages in infant mice. Fetuses in utero in the pregnant mice on gestational day (GD) 14 as well as male pups on postnatal day (PND) 2 and PND 8 were exposed either to filtered air (control; 0 ppm), or to 5 ppm or to 50 ppm of toluene for 5 consecutive days in the whole body exposure chamber. Immunological biomarkers in the blood and spleen of PND 21 male mice were examined by ELISA, real-time RT-PCR, flow cytometry, and histological analysis. Plasma total IgG1 levels were markedly reduced in PND 21 mice exposed to 5 ppm of toluene during all developmental stages. Splenic T lymphocyte subsets and mRNA expression levels of Th1 cytokine IL-12, transcription factor T-bet, and Foxp3 were significantly suppressed in PND 21 male mice exposed to toluene during PNDs 8-12. There were changes in some immunological biomarkers in PND 42 mice exposed to toluene during PNDs 8-12. These findings indicate developmental stage specific changes in non-specific immunological biomarkers in mice after early life toluene exposure. PMID- 22057033 TI - Glycomic analyses of ovarian follicles during development and atresia. AB - To examine the detailed composition of glycosaminoglycans during bovine ovarian follicular development and atresia, the specialized stromal theca layers were separated from the stratified epithelial granulosa cells of healthy (n=6) and atretic (n=6) follicles in each of three size ranges: small (3-5mm), medium (6 9mm) and large (10mm or more) (n=29 animals). Fluorophore-assisted carbohydrate electrophoresis analyses (on a per cell basis) and immunohistochemistry (n=14) were undertaken. We identified the major disaccharides in thecal layers and the membrana granulosa as chondroitin sulfate-derived ?uronic acid with 4-sulfated N acetylgalactosamine and ?uronic acid with 6-sulfated N-acetylgalactosamine and the heparan sulfate-derived Deltauronic acid with N-acetlyglucosamine, with elevated levels in the thecal layers. Increasing follicle size and atresia was associated with increased levels of some disaccharides. We concluded that versican contains 4-sulfated N-acetylgalactosamine and it is the predominant 4 sulfated N-acetylgalactosamine proteoglycan in antral follicles. At least one other non- or 6-sulfated N-acetylgalactosamine proteoglycan(s), which is not decorin or an inter-alpha-trypsin inhibitor family member, is present in bovine antral follicles and associated with hitherto unknown groups of cells around some larger blood vessels. These areas stained positively for chondroitin/dermatan sulfate epitopes [antibodies 7D4, 3C5, and 4C3], similar to stem cell niches observed in other tissues. The sulfation pattern of heparan sulfate glycosaminoglycans appears uniform across follicles of different sizes and in healthy and atretic follicles. The heparan sulfate products detected in the follicles are likely to be associated with perlecan, collagen XVIII or betaglycan. PMID- 22057035 TI - High levels of immunoglobulin E and a continuous increase in immunoglobulin G and immunoglobulin M by age in children with newly diagnosed type 1 diabetes. AB - The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p < 0.01) and higher IgA levels (p = 0.045), whereas no differences in IgE or IgM (p > 0.5) levels were found. Age-specific levels were unchanged over a 9-year period. In patients and siblings IgG, IgA and IgE increased by age (p < 0.001); which was in contrast to IgM (p > 0.05). The continued increase in IgG levels by age indicates that adult levels are reached later than in previously studied cohorts, thereby indicating a slower maturation of the immune system. PMID- 22057036 TI - Evaluation of the first immunoassay for the semi-quantitative measurement of meprobamate in human whole blood or plasma using biochip array technology. AB - BACKGROUND: Meprobamate is a carbamate, and the main metabolite of carisoprodol. It is used as an anxiolytic agent. Overdose of both drugs produces intoxication that is often serious and sometimes life threatening. However there was until now no immunoassay for the diagnosis of this intoxication. METHODS: A chemiluminescent immunoassay for the semi-quantitative measurement of meprobamate in human blood and plasma has recently been developed, using the Evidence Investigator system (Randox(r)). In this study, the immunoassay was evaluated by testing drug-free (n=10) or spiked whole blood and plasma samples (n=70), and authentic post mortem whole blood samples from deceased patients in which meprobamate was present (n=38) or not (n=10). A previously validated gas chromatography-mass spectrometry (GC-MS) method was used for confirmation and quantification. 97 psychoactive drugs including carisoprodol were analyzed for possible interference. RESULTS: With a cut-off at 0.5 mg/L, specificity, sensitivity and accuracy were 100%, 97.2% and 97.6%, respectively. All the untreated patients presented results under the cut-off. Meprobamate was not detected in three whole blood samples spiked with concentrations under the therapeutic range. In the authentic patients (n=48), there were no false-negative results. A good correlation was found between the immunoassay and GC-MS (r=0.90). Quantitative results of the immunoassay are approximately two-fold lower than GC MS results. Only carisoprodol presented a cross-reactivity, 38+/-6.6% at 10 mg/L, and 26+/-4.8% at 100mg/L. CONCLUSION: The first meprobamate immunoassay has shown very good specificity, selectivity and accuracy, which allow its use in hospital clinical laboratories for rapid diagnosis of meprobamate (or carisoprodol) intoxications. PMID- 22057037 TI - Identification of potential serum biomarkers for gastric cancer by a novel computational method, multiple normal tissues corrected differential analysis. AB - BACKGROUND: Genes specifically expressed in one or a few tissues and upregulated in tumors are potentially good serum biomarkers. METHODS: By applying a recently developed computational method, called multiple normal tissues corrected differential analysis (MNTDA), we identified genes that are likely to be upregulated in the blood of gastric cancer patients as compared to normal controls. RESULTS: We identified four genes (MMP-1, MMP-3, MMP-12, and CXCL5) as potential serum biomarkers for gastric cancer. Of these four genes, only MMP-1 was significantly upregulated in the sera of 40 gastric cancer patients, as compared to 40 control sera. The same pattern was observed in the second cohort of 80 gastric cancer patients and 80 controls. In a combined analysis, the level of serum MMP-1 in gastric cancer patients was significantly higher than the level in control samples (P<0.0001). The use of MMP-1 was 62.5% sensitive and 62.5% specific in detecting gastric cancer patients. Patients with high serum levels of MMP-1 had a significantly worse outcome than patients with low serum MMP-1 levels. Finally, we determined that preoperative serum MMP-1 levels were prognostic, independent of tumor stage. CONCLUSIONS: MMP-1 is a potential prognostic marker for gastric cancer patients after gastrectomy. PMID- 22057038 TI - PCR for monitoring of minimal residual disease in hematologic malignancy. AB - Monitoring minimal residual disease (MRD) is useful to evaluate therapeutic response and risk of relapse in patients with hematologic malignancy. Currently available quantitative MRD assays are fluorescence in situ hybridization of chromosomal aberrations; multiparameter flow cytometry of leukemia-associated immunophenotypes; and quantitative polymerase chain reaction (qPCR) analysis of fusion genes, immunoglobulin/T-cell receptor gene rearrangements, genetic alterations, or over-expressed genes. Among the PCR-based markers, genetic alterations are found in acute myelogenous leukemia patients with cytogenetically normal karyotype and can be considered as applicable targets for monitoring of MRD. Screening, confirmation and quantification procedures are important to develop the patient- or tumor-specific MRD assays using the PCR-based markers. Wild-type blocking PCR or coamplification at lower denaturing temperature-PCR is suited for screening of low-abundant genetic alterations, and allele-specific qPCR using primers including mismatched base and locked nucleic acids can quantify not only insertion and duplication of several nucleotides but also single nucleotide mutation in the presence of an excess amount of wild-type nucleotides. In addition to the well-established MRD markers, such as immunoglobulin/T-cell receptor gene rearrangements and fusion genes, utilizing potential MRD markers such as genetic alterations may expand the spectrum of patients in whom MRD can be monitored. PMID- 22057039 TI - Time course of cortisol loss in hair segments under immersion in hot water. AB - BACKGROUND: Hair cortisol is supposed to be a good biomarker of chronic stress. Major loss of hair cortisol in long-term exposure to environmental factors affected strongly its proper assessment of chronic stress in human. However, there was no research on time course of hair cortisol loss during the long-term exposure. METHODS: Hair samples with longer than 1cm in the posterior vertex region were cut as close as possible to the scalp. The 1-cm hair samples were treated by ultraviolet irradiation or immersion in shampoo solution or water immersion at 40, 65 and 80 degrees C. Hair cortisol content was determined with high performance liquid chromatography tandem mass spectrometry. RESULTS: Ultraviolet irradiation and immersion in shampoo solution and hot water gave rise to the significant cortisol loss in hair. Hair cortisol content was sharply decreased with water immersion duration during initial stage and slowly decreased in the following stage. CONCLUSIONS: The 2-stage loss process with water immersion duration modeled to some extent time course of hair cortisol loss in long-term exposure to external environments. Cortisol from hair samples closest to the scalp in the posterior vertex could represent more accurately central hypothalamo-pituitary-adrenal activity. PMID- 22057040 TI - Accurate automatic analysis of cardiac cine images. AB - Acquisition of noncontrast agent cine cardiac magnetic resonance (CMR) gated images through the cardiac cycle is, at present, a well-established part of examining cardiac global function. However, regional quantification is less well established. We propose a new automated framework for analyzing the wall thickness and thickening function on these images that consists of three main steps. First, inner and outer wall borders are segmented from their surrounding tissues with a geometric deformable model guided by a special stochastic speed relationship. The latter accounts for Markov-Gibbs shape and appearance models of the object-of-interest and its background. In the second step, point-to-point correspondences between the inner and outer borders are found by solving the Laplace equation and provide initial estimates of the local wall thickness and the thickening function index. Finally, the effects of the segmentation error is reduced and a continuity analysis of the LV wall thickening is performed through iterative energy minimization using a generalized Gauss-Markov random field (GGMRF) image model. The framework was evaluated on 26 datasets from clinical cine CMR images that have been collected from patients with eleven independent studies, with chronic ischemic heart disease and heart damage. The performance evaluation of the proposed segmentation approach, based on the receiver operating characteristic (ROC) and Dice similarity coefficients (DSC) between manually drawn and automatically segmented contours, confirmed a high robustness and accuracy of the proposed segmentation approach. Furthermore, the Bland-Altman plot is used to assess the limit of agreement of our measurements of the global function parameters compared to the ground truth. Importantly, comparative results on the publicly available database (MICCAI 2009 Cardiac MR Left Ventricle Segmentation) demonstrated a superior performance of the proposed segmentation approach over published methods. PMID- 22057041 TI - Sparse-grid-based adaptive model predictive control of HL60 cellular differentiation. AB - Quantitative methods such as model-based predictive control are known to facilitate the design of strategies to manipulate biological systems. This study develops a sparse-grid-based adaptive model predictive control (MPC) strategy to direct HL60 cellular differentiation. Sparse-grid sampling and interpolation support a computationally efficient adaptive MPC scheme in which multiple data consistent regions of the model parameter space are identified and used to calculate a control compromise. The algorithm is evaluated in silico with structural model mismatch. Simulations demonstrate how the multiscenario control strategy more effectively manages the mismatch compared to a single scenario approach. Furthermore, the controller is evaluated in vitro to differentiate HL60 cells in both normal and perturbed environments. The controller-derived input sequence successfully achieves and sustains the specified target level of granulocytes when implemented in the laboratory. The results and analysis given here imply that adoption of this experiment planning technique to direct cell differentiation within more complex tissue engineered constructs will require the use of a reasonably accurate mathematical model and an extension of this algorithm to multiobjective controller design. PMID- 22057042 TI - High time-resolved cardiac functional imaging using temporal regularization for small animal on a clinical 3T scanner. AB - Accurate assessment of mice cardiac function with magnetic resonance imaging is essential for longitudinal studies and for drug development related to cardiovascular diseases. Whereas dedicated small animal MR scanners are not readily available, it would be a great advantage to be able to perform cardiac assessment on clinical systems, in particular, in the context of translational research. However, mouse imaging remains challenging since it requires both high spatial and temporal resolutions, while gradient performances of clinical scanners often limit the reachable parameters. In this study, we propose a new cine sequence, named "interleaved cine," which combines two repetitions of a standard cine sequence shifted in time in order to reach resolution parameters compatible with mice imaging. More precisely, this sequence allows temporal resolution to be reduced to 6.8 ms instead of 13.5 ms initially imposed by the system's hardware. We also propose a two-step denoising algorithm to suppress some artifacts inherent to the new interleaved cine thus allowing an efficient enhancement of the image quality. In particular, we model and suppress the periodic intensity pattern and further denoise the sequence by soft thresholding of the temporal Fourier coefficients. This sequence was successfully validated with mass and function measurements on relevant mice models of cardiovascular diseases. PMID- 22057043 TI - RP-HPLC-ESI-MS evidenced that salivary cystatin B is detectable in adult human whole saliva mostly as S-modified derivatives: S-Glutathionyl, S-cysteinyl and S S 2-mer. AB - An HPLC-ESI-MS analysis of adult human whole saliva evidenced three protein masses (M average 11,487+/-2, 11,301+/-2 and 22,362+/-3Da) eluting in the 32.5 35.0min range. Treatment in reducing conditions allowed establishing that they are S-derivatives of N-terminal acetylated cystatin B, namely its S-glutathionyl, S-cysteinyl and S-S dimer. The identification was confirmed by high resolution HPLC-ESI-MS-MS experiments on the intact naturally occurring proteins and their tryptic digests. S-unmodified cystatin B is rarely detectable in whole saliva of healthy adults (5 subjects out of 65) and its percentage does not overcome approximately 20% of total cystatin B (11+/-9%). In the majority of subjects (60 out of 65) the mean percentages of the S-modified derivatives were S-glutathionyl 53+/-13%, S-cysteinyl 15+/-5%, S-S 2-mer 32+/-13%. Variations of the percentages of these S-modified derivatives of cystatin B could be indicative of oral oxidative stress. As we are aware, this is the first time that S glutathionylation and S-cysteinylation were described as extensive PTM of a salivary protein and the first time that these PTMs were detected in naturally occurring cystatin B. PMID- 22057044 TI - Proteomics combines morphological, physiological and biochemical attributes to unravel the survival strategy of Anabaena sp. PCC7120 under arsenic stress. AB - Proteomics in conjunction with morphological, physiological and biochemical variables has been employed for the first time to unravel survival strategies of the diazotrophic cyanobacterium Anabaena sp. PCC7120 under Arsenic (As) stress. Significant reduction in growth, carbon fixation, nitrogenase activity and chlorophyll content after 1 day (1d) and recovery after 15 days (15d) of As exposure indicates the acclimation of the test organism against As stress. The formation of akinete like structures is a novel observation never reported before in Anabaena sp. PCC7120. Proteomic characterization using 2-DE showed average 537, 422 and 439 spots in control, 1 and 15d treatment respectively. MALDI-TOF and LC-MS of As-treated Anabaena revealed a total of 45 differentially expressed proteins, of which 13 were novel (hypothetical) ones. Down-regulation of phosphoglycerate kinase (PGK), fructose bisphosphate aldolase II (FBA II), fructose 1,6 bisphosphatase (FBPase), transketolase (TK), and ATP synthase on day 1 and their significant recovery on the 15th day presumably maintained the glycolysis, pentose phosphate pathway (PPP) and turnover rate of Calvin cycle, hence survival of the test organism. Up-regulation of catalase (CAT), peroxiredoxin (Prx), thioredoxin (Trx) and oxidoreductase appears to protect the cells from oxidative stress. Appreciable induction in phytochelatin content (2.4 fold), GST activity (2.3 fold), and transcripts of phytochelatin synthase (5.0 fold), arsenate reductase (8.5 fold) and arsenite efflux genes - asr1102 (5.0 fold), alr1097 (4.7 fold) reiterates their role in As sequestration and shielding of the organism from As toxicity. While up-regulated metabolic and antioxidative defense proteins, phytochelatin and GST work synchronously, the ars genes play a central role in detoxification and survival of Anabaena under As stress. The proposed hypothetical model explains the interaction of metabolic proteins associated with the survival of Anabaena sp. PCC7120 under As stress. PMID- 22057045 TI - Phosphotyrosine mediated protein interactions of the discoidin domain receptor 1. AB - The receptor tyrosine kinase DDR1 has been implicated in multiple human cancers and fibrosis and is targeted by the leukemia drug Gleevec. This suggests that DDR1 might be a new therapeutic target. However, further insight into the DDR1 signaling pathway is required in order to support its further development. Here, we investigated DDR1 proximal signaling by the analysis of protein-protein interactions using proteomic approaches. All known interactors of DDR1 were identified and localized to specific phosphotyrosine residues on the receptor. In addition, we identified numerous signaling proteins as new putative phosphotyrosine mediated interactors including RasGAP, SHIP1, SHIP2, STATs, PI3K and the SRC family kinases. Most of the new proteins contain SH2 and PTB domains and for all interactors we could directly point the site of interaction to specific phosphotyrosine residues on the receptor. The identified proteins have roles in the early steps of the signaling cascade, propagating the signal from the DDR1 receptor into the cell. The map of phosphotyrosine mediated interactors of DDR1 created in this study will serve as a starting point for functional investigations which will enhance our knowledge on the role of the DDR1 receptor in health and disease. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry. PMID- 22057046 TI - Characterization of infections of human leukocytes by non-polio enteroviruses. AB - To elucidate the detailed susceptibilities of leukocytes to clinically important non-polio enteroviruses (EVs), primary monocytes and various human leukocyte cell lines were infected with coxsackievirus A24 (CVA24), coxsackievirus B3 (CVB3), and enterovirus 70 (EV70). The permissiveness was then assessed by determining virus replication and resultant cytopathic effects. Different EVs varied markedly in their ability to infect leukocyte cell lines. CVB3 replicated effectively in leukocytes of B-cell, T-cell, and monocyte origin, CVA24 in leukocytes of B-cell and monocyte origin, and EV70 in leukocytes of monocyte origin. Primary monocytes, as well as monocyte-derived U-937 cells, were permissive to all three EVs. We observed a positive correlation between cytotoxicity and active virus replication, except in CVB3-infected monocytes. U-937 cells efficiently generated CVB3 progeny virus without severe cellular damage, including cell death. Moreover, infectivity on leukocytes was not absolutely associated with the availability of viral receptors. These findings suggest that the susceptibility of human leukocytes to non-polio EVs may be responsible for virus transport during the viremic phase, particularly to secondary target organs, and that active replication of CVB3 in all human leukocyte lineages leads to greater dissemination, in agreement with the ability of CVB to cause systemic diseases. PMID- 22057048 TI - Porous 'Ouzo-effect' silica-ceria composite colloids and their application to aluminium corrosion protection. AB - By exploiting spontaneous emulsification to prepare porous SiO(2) particles, we report the formation of porous CeO(2)@SiO(2) hybrid colloids and their incorporation into a silica-zirconia coating to improve the corrosion protection of aluminium. PMID- 22057047 TI - Early stroke following acute myocardial infarction: incidence, predictors and outcome in six Middle-Eastern countries. AB - BACKGROUND AND OBJECTIVES: Stroke is a potential complication of acute myocardial infarction (AMI). The aim of this study was to identify the incidence, risk factors predisposing to stroke and in-hospital outcome during the index admission with AMI among patients in the Middle East. METHODS: For a period of 6 months in 2006 and 2007, 5,833 consecutive AMI patients were enrolled from 64 hospitals in 6 Middle East countries. RESULTS: The incidence of in-hospital stroke following AMI was 0.85%. Most cases were ST segment elevation AMI-related and ischemic in nature. Patients with in-hospital stroke were older than patients without stroke and were more likely to be female (36 vs. 18.6%, p = 0.0033). They were also more likely to have diabetes mellitus, dyslipidemia, prior AMI, or percutaneous/surgical coronary revascularization. Patients with stroke were more likely to present with advanced Killip class II-IV, higher mean heart rate and higher serum creatinine. Independent predictors of stroke were age, prior stroke, prior coronary artery bypass surgery, anterior AMI and systolic blood pressure >190 mm Hg on presentation. Early administration of statins was independently associated with reduced stroke risk (odds ratio, OR, 0.4, 95% confidence interval, CI, 0.19-0.90, p = 0.025). Stroke was fatal in 44% of the cases and was independently associated with in-hospital mortality (adjusted OR 12.5, 95% CI 5.7 27.4, p < 0.01). CONCLUSION: There is a low incidence of in-hospital stroke in Middle-Eastern patients presenting with AMI but with very high fatality rates. Early statin therapy was associated with a significant reduction in stroke risk. Future work should be focused on reducing the risk and improving the outcome of this devastating complication. PMID- 22057049 TI - A 4D statistical model of wrist bone motion patterns. AB - Direct imaging of ligament damage in the wrist remains a challenge. Still, such damage can be assessed indirectly through the analysis of changes in wrist pose and motion pattern. For this purpose we built a statistical reference model that describes healthy motion patterns. We show that such a model can also be used to detect and quantify pathologies. A model that only describes the global translations and rotations of the carpal bones is insufficiently accurate due to size and shape variations of the bones. We present a local statistical motion model that minimizes the influence of size and shape differences by analyzing the coordinate differences of pairs of points on adjacent bone surfaces. These differences are determined in a set of 14 healthy example wrists imaged in a range of poses by means of 4D-RX imaging. The distribution of the differences as a function of the pose form the local statistical motion model (LSMM). Translations of 2 mm and rotations of 20 degrees with respect to the healthy example wrists are detected as outliers in the point pair distributions. An evaluation involving wrists with a damaged ligament between scaphoid and lunate shows that not only joint space widenings can be detected, but also shifts of congruent bone surfaces. The LSMM is also used to perform a virtual reconstruction of the most likely healthy wrist after a simulated perturbation of bones. The reconstruction precision is shown to be about 1 mm. Therefore, the presented 4D statistical model of wrist bone movement may become a valuable clinical tool for diagnosis and surgical planning. PMID- 22057050 TI - Endoscopic video manifolds for targeted optical biopsy. AB - Gastro-intestinal (GI) endoscopy is a widely used clinical procedure for screening and surveillance of digestive tract diseases ranging from Barrett's Oesophagus to oesophageal cancer. Current surveillance protocol consists of periodic endoscopic examinations performed in 3-4 month intervals including expert's visual assessment and biopsies taken from suspicious tissue regions. Recent development of a new imaging technology, called probe-based confocal laser endomicroscopy (pCLE), enabled the acquisition of in vivo optical biopsies without removing any tissue sample. Besides its several advantages, i.e., noninvasiveness, real-time and in vivo feedback, optical biopsies involve a new challenge for the endoscopic expert. Due to their noninvasive nature, optical biopsies do not leave any scar on the tissue and therefore recognition of the previous optical biopsy sites in surveillance endoscopy becomes very challenging. In this work, we introduce a clustering and classification framework to facilitate retargeting previous optical biopsy sites in surveillance upper GI endoscopies. A new representation of endoscopic videos based on manifold learning, "endoscopic video manifolds" (EVMs), is proposed. The low dimensional EVM representation is adapted to facilitate two different clustering tasks; i.e., clustering of informative frames and patient specific endoscopic segments, only by changing the similarity measure. Each step of the proposed framework is validated on three in vivo patient datasets containing 1834, 3445, and 1546 frames, corresponding to endoscopic videos of 73.36, 137.80, and 61.84 s, respectively. Improvements achieved by the introduced EVM representation are demonstrated by quantitative analysis in comparison to the original image representation and principal component analysis. Final experiments evaluating the complete framework demonstrate the feasibility of the proposed method as a promising step for assisting the endoscopic expert in retargeting the optical biopsy sites. PMID- 22057051 TI - Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer. AB - BACKGROUND: The number of patients with chronic gastrointestinal (GI) symptoms after cancer therapies which have a moderate or severe impact on quality of life is similar to the number diagnosed with inflammatory bowel disease annually. However, in contrast to patients with inflammatory bowel disease, most of these patients are not referred for gastroenterological assessment. Clinicians who do see these patients are often unaware of the benefits of targeted investigation (which differ from those required to exclude recurrent cancer), the range of available treatments and how the pathological processes underlying side effects of cancer treatment differ from those in benign GI disorders. This paper aims to help clinicians become aware of the problem and suggests ways in which the panoply of syndromes can be managed. METHODS: A multidisciplinary literature review was performed to develop guidance to facilitate clinical management of GI side effects of cancer treatments. RESULTS: Different pathological processes within the GI tract may produce identical symptoms. Optimal management requires appropriate investigations and coordinated multidisciplinary working. Lactose intolerance, small bowel bacterial overgrowth and bile acid malabsorption frequently develop during or after chemotherapy. Toxin-negative Clostridium difficile and cytomegalovirus infection may be fulminant in immunosuppressed patients and require rapid diagnosis and treatment. Hepatic side effects include reactivation of viral hepatitis, sinusoidal obstruction syndrome, steatosis and steatohepatitis. Anticancer biological agents have multiple interactions with conventional drugs. Colonoscopy is contraindicated in neutropenic enterocolitis but endoscopy may be life-saving in other patients with GI bleeding. After cancer treatment, simple questions can identify patients who need referral for specialist management of GI symptoms. Other troublesome pelvic problems (eg, urinary, sexual, nutritional) are frequent and may also require specialist input. The largest group of patients affected by chronic GI symptoms are those who have been treated with pelvic radiotherapy. Their complex symptoms, often caused by more than one diagnosis, need systematic investigation by gastroenterologists when empirical treatments fail. All endoscopic and surgical interventions after radiotherapy are potentially hazardous as radiotherapy may induce significant local ischaemia. The best current evidence for effective treatment of radiation induced GI bleeding is with sucralfate enemas and hyperbaric oxygen therapy. CONCLUSIONS: All cancer units must develop simple methods to identify the many patients who need help and establish routine referral pathways to specialist gastroenterologists where patients can receive safe and effective treatment. Early contact with oncologists and/or specialist surgeons with input from the patient's family and friends often helps the gastroenterologist to refine management strategies. Increased training in the late effects of cancer treatment is required. PMID- 22057052 TI - Cognitive impairment in non-cirrhotic chronic liver disease is unrelated to liver disease severity but associated with ineffective baroreflex function. PMID- 22057053 TI - In silico feedback for in vivo regulation of a gene expression circuit. AB - We show that difficulties in regulating cellular behavior with synthetic biological circuits may be circumvented using in silico feedback control. By tracking a circuit's output in Saccharomyces cerevisiae in real time, we precisely control its behavior using an in silico feedback algorithm to compute regulatory inputs implemented through a genetically encoded light-responsive module. Moving control functions outside the cell should enable more sophisticated manipulation of cellular processes whenever real-time measurements of cellular variables are possible. PMID- 22057054 TI - Draft genome sequence of pigeonpea (Cajanus cajan), an orphan legume crop of resource-poor farmers. AB - Pigeonpea is an important legume food crop grown primarily by smallholder farmers in many semi-arid tropical regions of the world. We used the Illumina next generation sequencing platform to generate 237.2 Gb of sequence, which along with Sanger-based bacterial artificial chromosome end sequences and a genetic map, we assembled into scaffolds representing 72.7% (605.78 Mb) of the 833.07 Mb pigeonpea genome. Genome analysis predicted 48,680 genes for pigeonpea and also showed the potential role that certain gene families, for example, drought tolerance-related genes, have played throughout the domestication of pigeonpea and the evolution of its ancestors. Although we found a few segmental duplication events, we did not observe the recent genome-wide duplication events observed in soybean. This reference genome sequence will facilitate the identification of the genetic basis of agronomically important traits, and accelerate the development of improved pigeonpea varieties that could improve food security in many developing countries. PMID- 22057055 TI - Associations between multiple indicators of objectively-measured and self reported sedentary behaviour and cardiometabolic risk in older adults. AB - OBJECTIVE: To examine the associations between sedentary behaviour (SB) measured objectively and by self-report and cardiometabolic risk factors. METHOD: Cross sectional analyses of adults >=60 years who participated in the 2008 Health Survey for England. Main exposures were self-reported leisure-time SB consisting of TV/DVD viewing, non-TV leisure-time sitting, and accelerometry-measured SB. Outcomes included body mass index (BMI), waist circumference, cholesterol ratio (total/HDL), Hb1Ac and prevalent diabetes. RESULTS: 2765 participants (1256 men) had valid self-reported SB and outcomes/confounding variables data, of whom 649 (292 men) had accelerometer data. Total self-reported leisure-time SB showed multivariable-adjusted (including for moderate-to-vigorous physical activity) associations with BMI (beta for mean difference in BMI per 30 min/day extra SB: 0.088 kg/m(2), 95% CI 0.047 to 0.130); waist circumference (0.234, 0.129 to 0.339 cm); cholesterol ratio (0.018, 0.005 to 0.032) and diabetes (odds ratio per 30 min/day extra SB: 1.059, 1.030 to 1.089). Similar associations were observed for TV time while non-TV self-reported SB showed associations only with diabetes (1.057, 1.017 to 1.099). Accelerometry SB was associated with waist circumference only (0.633, 0.173 to 1.093). CONCLUSION: In older adults SB is associated with cardiometabolic risk factors, but the associations are more consistent when is measured by self-report that includes TV viewing. PMID- 22057057 TI - Anisotropic two-dimensional sheets assembled from rod-shaped metal complexes. AB - The facile formation of anisotropic two-dimensional sheets with different sizes, ranging from nanometre-scale to micrometre-scale, was achieved by the assembly of rod-shaped palladium complexes. PMID- 22057056 TI - Salt preference and mortality from stroke and coronary heart disease for Japanese men and women: the JACC study. AB - OBJECTIVE: The study aims to examine the association between salt preference and mortality from stroke and coronary heart disease (CHD). METHODS: Between 1988 and 1990, 35515 men and 49275 women aged 40-79 years completed a self-administered questionnaire in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by Monbusho. During a median duration of 16.4 years, 1970 stroke and 922 CHD deaths were observed. Salt preference was divided into three groups: low, moderate and high. RESULTS: Mortality rates per 1000 person-year from stroke were 2.0 for men, 1.3 for women and 1.6 for total subjects. The respective mortality from CHD was 1.1, 0.5 and 0.8, and that from total cardiovascular disease was 4.6, 2.9 and 3.6. Salt preference was positively associated with mortality from stroke for both sexes. The multivariable hazard ratios of stroke mortality for high versus low salt preference were 1.21(0.99-1.49) for men, 1.22(1.00-1.49) for women and 1.23(1.06-1.41) for total subjects. That positive association was primarily observed among male heavy drinkers (>= 46.0 g ethanol/day). Salt preference tended to be inversely associated with mortality from CHD. CONCLUSION: Salt preference was associated with increased mortality from stroke for both sexes, particularly for male heavy drinkers. PMID- 22057058 TI - Saponins do not affect the ecdysteroid receptor complex but cause membrane permeation in insect culture cell lines. AB - This project studied the effects of four saponins with a triterpenoid (Quillajasaponaria saponin and aescin) or steroid structure (digitonin and diosgenin which is the deglycosylated form of dioscin) on insect cells, namely Schneider S2 cells of Drosophila melanogaster (Diptera). A series of different experiments were performed to investigate potential mechanisms of action by saponins with regard to ecdysteroid receptor (EcR) responsiveness, cell viability, cell membrane permeation, and induction of apoptosis with DNA fragmentation and caspase-3 like activity. Major results were that (1) exposure of S2 cells containing an EcR-based reporter construct to a concentration series of each saponin scored no EcR activation, while (2) a loss of ecdysteroid signaling was observed with median inhibitory concentrations (IC(50)'s) of 3-50 MUM, and in parallel (3) a concentration-dependent change in loss of cell numbers in an cell viability assay with median effective concentrations (EC(50)'s) of 8 699 MUM. In continuation, it was of interest that (4) a trypan blue assay with Q. saponaria saponin confirmed the cell membrane permeation effect leading to cell toxicity with a median lethal concentration (LC(50)) value of 44 MUM, and interestingly this effect was very rapid. Another three interesting observations were that (5) exposure to 20E at 500 nM as used in the EcR-based report assay induced caspase-3 like activities which may help to explain the discrepancies between loss of EcR-responsiveness and cell viability, (6) low concentrations of saponins induced DNA fragmentation and caspase-3 like activities, confirming their potential to induce apoptosis, and (7) the saponin effects were counteracted with addition of cholesterol to the culture medium. In general the data obtained provide evidence that the anti-ecdysteroid action by saponins is not based on a true antagonistic interaction with EcR signaling, but can be explained by a cytotoxic action due to permeation of the insect cell membrane. PMID- 22057059 TI - A one-layer recurrent neural network for pseudoconvex optimization subject to linear equality constraints. AB - In this paper, a one-layer recurrent neural network is presented for solving pseudoconvex optimization problems subject to linear equality constraints. The global convergence of the neural network can be guaranteed even though the objective function is pseudoconvex. The finite-time state convergence to the feasible region defined by the equality constraints is also proved. In addition, global exponential convergence is proved when the objective function is strongly pseudoconvex on the feasible region. Simulation results on illustrative examples and application on chemical process data reconciliation are provided to demonstrate the effectiveness and characteristics of the neural network. PMID- 22057060 TI - Incremental learning from stream data. AB - Recent years have witnessed an incredibly increasing interest in the topic of incremental learning. Unlike conventional machine learning situations, data flow targeted by incremental learning becomes available continuously over time. Accordingly, it is desirable to be able to abandon the traditional assumption of the availability of representative training data during the training period to develop decision boundaries. Under scenarios of continuous data flow, the challenge is how to transform the vast amount of stream raw data into information and knowledge representation, and accumulate experience over time to support future decision-making process. In this paper, we propose a general adaptive incremental learning framework named ADAIN that is capable of learning from continuous raw data, accumulating experience over time, and using such knowledge to improve future learning and prediction performance. Detailed system level architecture and design strategies are presented in this paper. Simulation results over several real-world data sets are used to validate the effectiveness of this method. PMID- 22057061 TI - Quantitative analysis of nonlinear embedding. AB - A lot of nonlinear embedding techniques have been developed to recover the intrinsic low-dimensional manifolds embedded in the high-dimensional space. However, the quantitative evaluation criteria are less studied in literature. The embedding quality is usually evaluated by visualization which is subjective and qualitative. The few existing evaluation methods to estimate the embedding quality, neighboring preservation rate for example, are not widely applicable. In this paper, we propose several novel criteria for quantitative evaluation, by considering the global smoothness and co-directional consistence of the nonlinear embedding algorithms. The proposed criteria are geometrically intuitive, simple, and easy to implement with a low computational cost. Experiments show that our criteria capture some new geometrical properties of the nonlinear embedding algorithms, and can be used as a guidance to deal with the embedding of the out of-samples. PMID- 22057062 TI - Real-time vector quantization and clustering based on ordinary differential equations. AB - This brief presents a dynamical system approach to vector quantization or clustering based on ordinary differential equations with the potential for real time implementation. Two examples of different pattern clusters demonstrate that the model can successfully quantize different types of input patterns. Furthermore, we analyze and study the stability of our dynamical system. By discovering the equilibrium points for certain input patterns and analyzing their stability, we have shown the quantizing behavior of the system with respect to its vigilance parameter. The proposed system is applied to two real-world problems, providing comparable results to the best reported findings. This validates the effectiveness of our proposed approach. PMID- 22057063 TI - Optimal tracking control for a class of nonlinear discrete-time systems with time delays based on heuristic dynamic programming. AB - In this paper, a novel heuristic dynamic programming (HDP) iteration algorithm is proposed to solve the optimal tracking control problem for a class of nonlinear discrete-time systems with time delays. The novel algorithm contains state updating, control policy iteration, and performance index iteration. To get the optimal states, the states are also updated. Furthermore, the "backward iteration" is applied to state updating. Two neural networks are used to approximate the performance index function and compute the optimal control policy for facilitating the implementation of HDP iteration algorithm. At last, we present two examples to demonstrate the effectiveness of the proposed HDP iteration algorithm. PMID- 22057064 TI - A comparison of information functions and search strategies for sensor planning in target classification. AB - This paper investigates the comparative performance of several information-driven search strategies and decision rules using a canonical target classification problem. Five sensor models are considered: one obtained from classical estimation theory and four obtained from Bernoulli, Poisson, binomial, and mixture-of-binomial distributions. A systematic approach is presented for deriving information functions that represent the expected utility of future sensor measurements from mutual information, Renyi divergence, Kullback-Leibler divergence, information potential, quadratic entropy, and the Cauchy-Schwarz distance. The resulting information-driven strategies are compared to direct search, alert-confirm, task-driven (TS), and log-likelihood-ratio (LLR) search strategies. Extensive numerical simulations show that quadratic entropy typically leads to the most effective search strategy with respect to correct classification rates. In the presence of prior information, the quadratic-entropy driven strategy also displays the lowest rate of false alarms. However, when prior information is absent or very noisy, TS and LLR strategies achieve the lowest false-alarm rates for the Bernoulli, mixture-of-binomial, and classical sensor models. PMID- 22057065 TI - Video distribution techniques over WiMAX networks for m-Health applications. AB - In this paper, we propose a novel approach for video distribution over IEEE 802.16 networks for mobile Healthcare (m-Health) applications. The technique incorporates resource distribution, scheduling, and content-aware video streaming taking advantage of a flexible quality of service functionality offered by IEEE 802.16/WiMAX technology. The proposed technique is thoroughly investigated using network simulator software under various real-life m-Health scenarios, which include streaming video over medium access control layer service connections. It is shown that the technique is fully compatible with the WiMAX standard specification and allows a 9-16% increase in the overall network throughput, which is dependent upon the initial system configuration and the selection of WiMAX user parameters. PMID- 22057066 TI - Oxidative stress in kidney transplantation: causes, consequences, and potential treatment. AB - Oxidative stress is a major mediator of adverse outcomes throughout the course of transplantation. Transplanted kidneys are prone to oxidative stress-mediated injury by pre-transplant and post-transplant conditions that cause reperfusion injury or imbalance between oxidants and antioxidants. Besides adversely affecting the allograft, oxidative stress and its constant companion, inflammation, cause cardiovascular disease, cancer, metabolic syndrome, and other disorders in transplant recipients. Presence and severity of oxidative stress can be assessed by various biomarkers produced from interaction of reactive oxygen species with lipids, proteins, nucleic acids, nitric oxide, glutathione, etc. In addition, expression and activities of redox-sensitive molecules such as antioxidant enzymes can serve as biomarkers of oxidative stress. Via activation of nuclear factor kappa B, oxidative stress promotes inflammation which, in turn, amplifies oxidative stress through reactive oxygen species generation by activated immune cells. Therefore, inflammation markers are indirect indicators of oxidative stress. Many treatment options have been evaluated in studies conducted at different stages of transplantation in humans and animals. These studies have provided useful strategies for use in donors or in organ preservation solutions. However, strategies tested for use in post-transplant phase have been largely inconclusive and controversial. A number of therapeutic options have been exclusively examined in animal models and only a few have been tested in humans. Most of the clinical investigations have been of short duration and have provided no insight into their impact on the long-term survival of transplant patients. Effective treatment of oxidative stress in transplant population remains elusive and awaits future explorations. PMID- 22057067 TI - Malignant peripheral nerve sheath tumor of kidney. PMID- 22057068 TI - Distribution of albuminuria and low glomerular filtration rate in a rural area, Shahreza, Iran. AB - INTRODUCTION: Chronic kidney disease (CKD) is becoming a major public health problem worldwide. A remarkable part of health budget is designated annually to control end-stage renal disease in most countries. The aim of this study was to screen for CKD among the general population of the rural area of Shahreza, in the central region of Iran. MATERIALS AND METHODS: In a study of rural area around Shahreza, Iran, in 2009, a total of 1400 participants aged over 30 years old were selected by systematic randomized sampling. Glomerular filtration rate (GFR) was used as an index of kidney function and albuminuria, as an index of kidney damage. The simplified Modification of Diet in Renal Disease Study equation was used for estimation of GFR. RESULTS: A GFR less than 60 mL/min/m2 was found in 4.7% of the study population (1.8% in men and 6.1% in women). Microalbuminuria and macroalbuminuria were present in 16.2% of the participants (15% of men and 16.8% of women). Pyuria and hematuria rates were 12.3% and 12.6%. The prevalence of a GFR less than 60 mL/min/1.73 m2 was significantly increasing by age groups in both genders. CONCLUSIONS: Considering its high prevalence, CKD needs measures to identify the disease sooner and requires an active national screening program to identify patients in earlier stages. It seems reasonable to integrate such programs in the primary healthcare system. PMID- 22057069 TI - Prognostic value of renal pathological findings in children with atypical hemolytic uremic syndrome. AB - INTRODUCTION: Atypical hemolytic uremic syndrome (HUS) is accompanied by a poor prognosis and high mortality rate. We investigated the predictive value of severity of renal involvement, as evaluated by pathologic examination, for long term outcome of atypical HUS. MATERIALS AND METHODS: Kidney biopsies of 29 children diagnosed with atypical HUS between 1992 and 2005 were reviewed. The severity of glomerular, vascular (arteriolar and arterial), interstitial, and tubular involvement were determined. Scores of renal involvement were determined by re-evaluating kidney specimens. The outcome measures were death, chronic kidney disease (CKD), hypertension, and proteinuria. RESULTS: After a mean of 3.7 years of follow-up, 24.1% of the patients had normal kidney function and blood pressure, 24.1% showed proteinuria, and 41.4% had CKD, and 10.3% had unknown prognosis. Overall, 24.1% of the patients died due to emergent hypertension with or without CKD. The existence of arteriolar and arterial thrombosis attributed to severe CKD (risk ratio, 3.67; 95% confidence interval, 1.63 to 8.2). Presence of thrombosis in the vessels, and thickening of the arterial medial and intimal layers had brought about a significantly higher mortality rate. Chronic kidney disease was more frequent in the children with vascular scores higher than 0.14 and a final score of more than 0.2. CONCLUSIONS: The severity of renal pathological involvement, especially the degree of vascular damage, is a good predictor of long-term outcome of patient with atypical HUS. PMID- 22057070 TI - Doppler ultrasonography as a predictive tool for permanent kidney damage following acute pyelonephritis: comparison with dimercaptosuccinic acid scintigraphy. AB - INTRODUCTION: The aim of this study was to investigate power Doppler ultrasonography for diagnosis and prediction of scarring compared with technetium Tc 99m dimercaptosuccinic acid scintigraphy in acute pyelonephritis. MATERIALS AND METHODS: Sixty-six children, aged 2 months to 6 years old, admitted with clinical and biological signs of their first febrile urinary tract infection were studied. All of the children underwent PDU and technetium Tc 99m dimercaptosuccinic acid scintigraphy within 7 days after diagnosis and repeat scintigraphy at least 6 months later, if results of the first study were abnormal. Scintigraphic and Doppler studies were interpreted and compared. RESULTS: Dimercaptosuccinic acid scintigraphy demonstrated scar in 7.6% of renal units, 3.1% of patients without reflux and 66.7% of those with high-grade reflux. Kidneys with permanent kidney damage had a mean resistive index (RI) of 0.71 +/- 0.06, while the RI value for nonscarred kidneys was 0.66 +/- 0.06 (P = .02). The best cutoff point of RI value was 0.715, with a sensitivity of 70%, a specificity of 87.7%, and positive and negative predictive values of 32% and 97%, respectively. These values significantly increased when grey-scale ultrasonography findings were brought into account. Reflux was observed in 19.7% of renal units, which were associated with significantly higher RI values (P = .05). CONCLUSIONS: Power Doppler ultrasonography with a cutoff value of 0.715 has a reasonable sensitivity and specificity for prediction of renal scarring in young children with febrile urinary tract infection. PMID- 22057071 TI - Association of tumor necrosis factor-alpha gene polymorphisms with juvenile systemic lupus erythematosus nephritis in a cohort of egyptian patients. AB - INTRODUCTION: The production of tumor necrosis factor (TNF)-alpha has been deeply deregulated in systemic lupus erythematosus. We evaluated the association of 863C>A and -1031T>C polymorphisms of the TNF gene with susceptibility to and clinical manifestations of juvenile systemic lupus erythematosus. MATERIALS AND METHODS: This study was performed on 70 juvenile patients with systemic lupus erythematosus (mean age, 13.0 +/- 4.2 years). Ninety age- and sex-matched children served as a controls. All participants were genotyped for the TNF 863C>A and -1031T>C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism method. Analysis of serum TNF-alpha was done by solid-phase sandwich enzyme immunoassay. RESULTS: The mean serum TNF-alpha was significantly higher in the SLE patients compared to controls (P < .001). Regarding all participants, the mean serum TNF-alpha was significantly higher in children with -863AA genotype compared to carriers of -863C allele (P < .001). The TNF -863AA genotype frequencies were significantly higher in the patients group compared with the controls (P = .005) and were associated with increased risk for SLE development (odds ratio, 4.05; 95% confidence interval, 1.38 to 13.13; P = .005). The -863AA variant was associated with nephritis (P < .001) and Raynaud phenomenon (P = .001). CONCLUSIONS: The -863A allele of the TNF gene can be used as a genetic marker for SLE susceptibility and was associated with high TNF-alpha production, Raynaud phenomenon, and nephritis in juvenile SLE Egyptian patients. PMID- 22057072 TI - Fractional excretion of urea in pre-eclampsia: a clinical observation. AB - INTRODUCTION: Pre-eclampsia is one of the leading causes of maternal and fetal mortality and morbidity. It occurs in 7% of all the pregnancies and accounts for 80% of the cases of pregnancy-induced hypertension. Diagnosis of pre-eclampsia in patients with pre-existing chronic kidney disease, proteinuria, and hypertension is a dilemma. The fractional excretion of urea has been described as a marker for renal perfusion. Since pre-eclampsia is associated with a marked decline in renal perfusion, we explored the utility of the fractional excretion of urea as a marker for pre-eclampsia. MATERIALS AND METHODS: Urine and serum chemistries were evaluated in 6 pregnant women with pre-eclampsia on their first visit, immediately prior to delivery, and postpartum. For each of these three measurements, the fractional excretion of urea was calculated and proteinuria was assessed by random urine protein-creatinine ratio or 24-hour urine protein studies. RESULTS: In patients diagnosed with pre-eclampsia, the fractional excretion of urea decreased substantially from higher values obtained during the 3rd trimester to values consistent with renal hypoperfusion (< 35%) just prior to delivery, and it rapidly normalized immediately after delivery. CONCLUSIONS: Alterations in fractional excretion of urea, which suggest a decreased renal perfusion, may be a useful tool in supporting the diagnosis of preeclampsia. PMID- 22057073 TI - Comparing effects of clonazepam and zolpidem on sleep quality of patients on maintenance hemodialysis. AB - INTRODUCTION: Poor sleep quality is very common among maintenance hemodialysis patients and has negative impacts on patients' quality of life. Benzodiazepines have traditionally been used in this population; however, they may induce physical dependence and sleep apnea. Nonbenzodiazepine hypnotic medications with less side effects are introduced as alternatives. This study was designed to compare the effect of zolpidem and clonazepam on sleep quality of hemodialysis patients. MATERIALS AND METHODS: In a randomized crossover study on 23 hemodialysis patients, sleep quality was assessed using the Pittsburgh Sleep Quality Index at baseline, at the initiation of a 1-week washout period after a 2 week treatment with zolpidem (1 mg) and clonazepam (5 mg to 10 mg), and after the second 2 weeks of treatment. Patients who suffer from any concurrent situations that may affect sleep quality or psychiatric disorders and those on medications affecting sleep quality were excluded. RESULTS: The prevalence of poor sleep quality was 87.8% of the 88 hemodialysis patients who were initially approached. There was a significant negative correlation between iron deficiency and poor sleep quality. Both clonazepam and zolpidem significantly improved sleep quality; however, clonazepam was more effective in decreasing the Pittsburgh Sleep Quality Index scores (P = .03). Zolpidem was better tolerated in the hemodialysis patients. CONCLUSIONS: Clonazepam was more effective than zolpidem in the improvement of sleep quality of hemodialysis patients, while zolpidem was better tolerated in these patients. PMID- 22057074 TI - Effect of vitamin C on parathyroid hormone in hemodialysis patients with mild to moderate secondary hyperparathyroidism. AB - INTRODUCTION: In end-stage renal disease, there is a high incidence of secondary hyperparathyroidism. It is proposed that increasing vitamin C levels by dietary supplementation results in a decrease of parathyroid hormone (PTH) in vitamin C deficient hemodialysis patients with secondary hyperparathyroidism. The aim of this study was the evaluation of vitamin C administration for reduction of serum PTH level in hemodialysis patients. MATERIALS AND METHODS: Twenty-one hemodialysis patients with serum PTH levels less than 550 pg/mL (but more than 200 pg/mL) were administered intravenous vitamin C, 200 mg, 3 times per week for 3 months. Blood samples for measurement of PTH were obtained at the beginning of the hemodialysis session every month for three months. RESULTS: The mean level of serum biointact PTH was 333.3 +/- 141.3 pg/mL (reference range, 7 pg/mL to 82 pg/mL) at baseline, and it decreased to 256.5 +/- 137.2 pg/mL at 1 month (P = .03). The mean PTH level was also lower than the baseline value at 2 months (260.1 +/- 123.2 pg/mL, P = .03), while it increased to 328.9 +/- 176.0 pg/mL at 3 months, which was still slightly lower than the baseline level (P = .13). In 15 patients (71.4%), serum levels of PTH were lower than the baseline at months 1 to 2, while in the remaining 6 (28.6%), it was higher than the baseline value. At 3 months, 5 of the 15 patients with lower PTH levels up to the 3rd month experienced an increase in these levels again. CONCLUSIONS: Administration of intravenous vitamin C in hemodialysis patients noticeably decreased level of PTH, but its effect gradually diminished. PMID- 22057075 TI - Urinary tract infection after kidney transplantation in children and adolescents. AB - INTRODUCTION: Urinary tract infection (UTI) is common after pediatric kidney transplantation. The purpose of this study was to evaluate the prevalence of UTI and its risk factors in children and adolescents with kidney transplantation in Shiraz Transplant Center. MATERIALS AND METHODS: All children with kidney transplantation from 1992 to 2008 who were under regular follow-up were included in this retrospective study. Confirmed episodes of UTI after the 1st month of kidney transplantation were reviewed. RESULTS: Of the 216 patients younger than 19 years at the time of transplantation, 138 were included. The mean age at the time of kidney transplantation was 13.6 +/- 3.5 years. Urinary tract infection was documented in 24 patients (15 girls and 9 boys), of whom 12 experienced 1 episode, 4 had 2 episodes, and 8 had more than 2 episodes, during a median follow up period of 54 months. Of the patients with UTI, 14 (58%) had urinary reflux obstruction disorders as the primary kidney disease, 6 (25%) had suffered hereditary diseases, 3 (12.5%) had glomerular disease, and 1 (4.5%) had a urinary calculus. Occurrence of UTI was not significantly different among children with different primary kidney disease (P = .22). Despite using prophylactic antibiotics after the 1st month of kidney transplantation in all 5 patients with neurogenic bladder, they all experienced recurrent UTI. CONCLUSIONS: Despite discontinuation of antibiotic therapy, UTI was uncommon in children after the first month of transplantation. Two significant risk factors for UTI were female gender and neurogenic bladder in this transplant population. PMID- 22057076 TI - Comparison of alendronate and pamidronate on bone loss in kidney transplant patients for the first 6 months of transplantation. AB - INTRODUCTION: Osteoporosis develops and progresses in a considerable number of kidney transplant patients. Bisphosphonates, which are used for prevention and treatment of osteoporosis, may accentuate gasterointestinal complications and lead to more nonadherence to treatment. This randomized clinical trial was conducted to compare the effect of pamidronate versus alendronate on early bone mineral density changes in kidney transplant patients. MATERIALS AND METHODS: Forty patients (27 men and 13 women), aged from 20 to 58 years, with low bone mineral density (T score < -2) in the spine, total hip, or femur neck were enrolled. Participants were randomly allocated into 2 groups to receive pamidronate or alendronate. The pamidronate group received intravenous pamidronate, 90 mg, starting from the 3rd week of transplantation for 3 months. The alendronate group started to receive oral alendronate, 70 mg per week for the same period. At baseline and 6 months, bone mineral density was measured by dual energy x-ray absorptiometry. Gastrointestinal side effects were monitored every month. RESULTS: No significant difference was found in bone density changes of the lumber area between the two groups; however, significantly less reduction in bone mineral density of the femur neck and femur occurred in the pamidronate group. Kidney function and parathyroid hormone levels were similar in the two groups before and after the study. Gastrointestinal side effects were seen in 3 patients of the alendronate group only. CONCLUSIONS: Pamidronate was comparable to alendronate in prevention of early bone loss after kidney transplantation. PMID- 22057077 TI - A 22-year-old woman with hypertension and hypokalemia due to a juxtaglomerular cell tumor. AB - Secondary hypertension is responsible for less than 10% of cases of hypertension. If associated with hypokalemia, it may be due to primary or secondary hyperaldostronism, the latter being rarely caused by renin-secreting tumors. We present a 22-year-old woman with a history of hypertension and repeated hypokalemia, who was finally diagnosed with a small renin-secreting tumor after extensive paraclinical workup and imaging studies. PMID- 22057078 TI - Recurrence of primary hyperoxaluria after kidney transplantation. AB - Primary hyperoxaluria is a genetic disorder in glyoxylate metabolism that leads to systemic overproduction of oxalate. Functional deficiency of alanine glyoxylate aminotransferase in this disease leads to recurrent nephrolithiasis, nephrocalcinosis, systemic oxalosis, and kidney failure. We present a young woman with end-stage renal disease who received a kidney allograft and experienced early graft failure presumed to be an acute rejection. There was no improvement in kidney function, and she was required hemodialysis. Ultimately, biopsy revealed birefringent calcium oxalate crystals, which raised suspicion of primary hyperoxaluria. Further evaluations including genetic study and metabolic assay confirmed the diagnosis of primary hyperoxaluria type 1. This suggests a screening method for ruling out primary hyperoxaluria in suspected cases, especially before planning for kidney transplantation in patients with end-stage renal disease who have nephrocalcinosis, calcium oxalate calculi, or a family history of primary hyperoxaluria. PMID- 22057081 TI - Modulation of Bmp4 signalling in the epithelial-mesenchymal interactions that take place in early thymus and parathyroid development in avian embryos. AB - Epithelial-mesenchymal interactions are crucial for the development of the endoderm of the pharyngeal pouches into the epithelia of thymus and parathyroid glands. Here we investigated the dynamics of epithelial-mesenchymal interactions that take place at the earliest stages of thymic and parathyroid organogenesis using the quail-chick model together with a co-culture system capable of reproducing these early events in vitro. The presumptive territories of thymus and parathyroid epithelia were identified in three-dimensionally preserved pharyngeal endoderm of embryonic day 4.5 chick embryos on the basis of the expression of Foxn1 and Gcm2, respectively: the thymic rudiment is located in the dorsal domain of the third and fourth pouches, while the parathyroid rudiment occupies a more medial/anterior pouch domain. Using in vitro quail-chick tissue associations combined with in ovo transplantations, we show that the somatopleural but not the limb bud mesenchyme, can mimic the role of neural crest derived pharyngeal mesenchyme to sustain development of these glands up to terminal differentiation. Furthermore, mesenchymal-derived Bmp4 appears to be essential to promote early stages of endoderm development during a short window of time, irrespective of the mesenchymal source. In vivo studies using the quail chick system and implantation of growth factor soaked-beads further showed that expression of Bmp4 by the mesenchyme is necessary during a 24 h-period of time. After this period however, Bmp4 is no longer required and another signalling factor produced by the mesenchyme, Fgf10, influences later differentiation of the pouch endoderm. These results show that morphological development and cell differentiation of thymus and parathyroid epithelia require a succession of signals emanating from the associated mesenchyme, among which Bmp4 plays a pivotal role for triggering thymic epithelium specification. PMID- 22057082 TI - Determination of vertebral and femoral trabecular morphology and stiffness using a flat-panel C-arm-based CT approach. AB - The importance of assessing trabecular architecture together with bone mineral density to determine bone stiffness and fracture risk in osteoporosis has been well established. However, no imaging modalities are available to assess trabecular architecture at clinically relevant sites in the axial skeleton. Recently developed flat-panel CT devices, however, offer resolutions that are potentially good enough to resolve bone architecture at these sites. The goal of the present study was to investigate how accurate trabecular architecture and stiffness can be determined based on images from such a device (XperCT, Philips Healthcare). Ten cadaver human C3 vertebrae, twelve T12 vertebrae and 12 proximal femora were scanned with XperCT while mimicking in-vivo scanning conditions and compared to scans of the same bones with microCT. Standard segmentation and morphology quantification algorithms were applied as well as finite element (FE) simulation based on segmented and gray value images. Results showed that mean trabecular separation (Tb.Sp) and number (Tb.N) can be accurately determined at all sites. The accuracy of other parameters, however, depended on the site. For T12 no other structural parameters could be accurately quantified and no FE results could be obtained from segmented images. When using gray-level images, however, accurate determination of cancellous bone stiffness was possible. For the C3 vertebrae and proximal femora, mean bone volume fraction (BV/TV), Tb.Sp, Tb.N, and anisotropy (C3 only) could be determined accurately. For Tb.Th, structure model index (SMI, femur only), and anisotropy good correlations were obtained but the values were not determined accurately. FE simulations based on segmented images were accurate for the C3 vertebrae, but severely underestimated bone stiffness for the femur. Here also, this was improved by using the gray value models. In conclusion, XperCT does provide a resolution that is good enough to determine trabecular architecture, but the signal to noise ratio is key to the accuracy of the morphology measurement. When the trabeculae are thick e.g. in the femur or the noise is low, e.g. cervical spine, architecture and stiffness could be determined accurately, but when the trabeculae are thin and the noise is high, e.g. thoracic spine, architecture could not be determined accurately and the connectivity was lost and hence no mechanical properties could be calculated directly. PMID- 22057083 TI - Ultrastructure of regenerated bone mineral surrounding hydroxyapatite-alginate composite and sintered hydroxyapatite. AB - We report the ultrastructure of regenerated bone surrounding two types of biomaterials: hydroxyapatite-alginate composite and sintered hydroxyapatite. Critical defects in the calvaria of Wistar rats were filled with micrometer-sized spherical biomaterials and analyzed after 90 and 120 days of implantation by high resolution transmission electron microscopy and Fourier transform infrared attenuated total reflectance microscopy, respectively. Infrared spectroscopy showed that hydroxyapatite of both biomaterials became more disordered after implantation in the rat calvaria, indicating that the biological environment induced modifications in biomaterials structure. We observed that the regenerated bone surrounding both biomaterials had a lamellar structure with type I collagen fibers alternating in adjacent lamella with angles of approximately 90 degrees . In each lamella, plate-like apatite crystals were aligned in the c-axis direction, although a rotation around the c-axis could be present. Bone plate like crystal dimensions were similar in regenerated bone around biomaterials and pre-existing bone in the rat calvaria. No epitaxial growth was observed around any of the biomaterials. A distinct mineralized layer was observed between new bone and hydroxyapatite-alginate biomaterial. This region presented a particular ultrastructure with crystallites smaller than those of the bulk of the biomaterial, and was possibly formed during the synthesis of alginate-containing composite or in the biological environment after implantation. Round nanoparticles were observed in regions of newly formed bone. The findings of this work contribute to a better understanding of the role of hydroxyapatite based biomaterials in bone regeneration processes at the nanoscale. PMID- 22057084 TI - Analysis of the interactions between Eudragit(r) L100 and porcine pancreatic trypsin by calorimetric techniques. AB - Flexible-chain polymers with charge (polyelectrolytes) can interact with globular proteins with a net charge opposite to the charge of the polymers forming insoluble complexes polymer-protein. In this work, the interaction between the basic protein trypsin and the anionic polyelectrolyte Eudragit((r)) L100 was studied by using isothermal calorimetric titrations and differential scanning calorimetry. Turbidimetric assays allowed determining that protein-polymer complex was insoluble at pH below 5 and the trypsin and Eudragit((r)) L100 concentrations required forming the insoluble complex. DSC measurements showed that the T(m) and denaturalization heat of trypsin increased in the polymer presence and the complex unfolded according to a two-state model. DeltaH degrees and DeltaS degrees binding parameters obtained by ITC were positives agree with hydrophobic interaction between trypsin and polymer. However, ionic strength of 1.0M modified the insoluble complex formation. We propose a mechanism of interaction between Eudragit((r)) L100 and trypsin molecules that involves both hydrophobic and electrostatic interactions. Kinetic studies of complex formation showed that the interaction requires less than 1 min achieving the maximum quantity of complex. Finally, a high percentage of active trypsin was precipitated (approximately 76% of the total mass of protein). These findings could be useful in different protocols such as a protein isolation strategy, immobilization or purification of a target protein. PMID- 22057085 TI - 5alpha-reductase inhibitors, antiviral and anti-tumor activities of some steroidal cyanopyridinone derivatives. AB - We herein report the 5alpha-reductase inhibitors, antiviral and anti-tumor activities of some synthesized heterocyclic cyanopyridone and cyanothiopyridone derivatives fused with steroidal structure. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds, except 3b, were interestingly less toxic than the reference drug (Prednisolone((r))). Seventeen heterocyclic derivatives containing a cyanopyridone or cyanothiopyridone rings fused to a steroidal moiety were synthesized and screened for their 5alpha-reductase inhibitors, antiviral and anti-tumor activities comparable to that of Anastrozole, Bicalutamide, Efavirenz, Capravirine, Ribavirin, Oseltamivir and Amantadine as the reference drugs. Some of the compounds exhibited better 5alpha-reductase inhibitors, antiviral and anti tumor activities than the reference drugs. The detailed 5alpha-reductase inhibitors, antiviral and anti-tumor activities of the synthesized compounds were reported. PMID- 22057086 TI - Decarboxylative benzylation and arylation of nitriles. AB - Decarboxylative benzylation of nitriles is achieved via coupling of metallated nitriles with Pd-pi-benzyl complexes that are generated in situ from cyanoacetic benzyl esters. In addition, decarboxylative couplings of alpha,alpha disubstituted 2-methylfuranyl cyanoacetates can lead to either decarboxylative arylation or benzylation depending on the reaction conditions. PMID- 22057087 TI - Oil based nanocarrier system for transdermal delivery of ropinirole: a mechanistic, pharmacokinetic and biochemical investigation. AB - Ropinirole, a recent introduction in the clinical treatment of Parkinson's disease, suffers with the problems of low oral bioavailability and frequent dosing. An effective transdermal nano-emulsion drug delivery system can however resolve these issues effectively with greater therapeutic benefits and clinical significance. Therefore, the present work focuses precisely on pharmacokinetic, biochemical and mechanistic assessment of transdermal nanoemulsion gel in rats induced with Parkinson lesioned brain by 6-OHDA. DSC and FT-IR studies showed that NEG affects the normal lipid packing of stratum corneum to enhance the drug permeation. Study of pharmacokinetic parameters (AUC, C(max), and T(max)) revealed a greater and more extended release of ropinirole from nanoemulsion gel compared to that from a conventional gel (RPG) and oral marketed tablet (Ropitor). The AUC(0->infinity) for RPCNG and RPTNG was found to be 928.07 +/- 206.5 and 1055.99 +/- 251.7 ngh/mL, respectively in comparison to 137.25 +/- 31.3 and 467.15 +/- 106.1 ngh/mL for RPG and oral tablet, respectively. The relative bioavailability of ropinirole has been enhanced more than two fold by RPTNG. Furthermore, antiparkinson activity was evaluated in terms of estimating the level of thiobarbituric acid reactive substances, glutathione antioxidant enzymes and catalase in lesioned brain of rats. Formulations were also found to be non toxic and non-irritant by histological investigations. PMID- 22057088 TI - Can mortality data provide reliable indicators for Creutzfeldt-Jakob disease surveillance? A study in France from 2000 to 2008. AB - BACKGROUND: Surveillance of Creutzfeldt-Jakob disease (CJD) is still an important issue because of the variant CJD epidemic, which is in decline and also because of the emergence of novel forms of animal transmissible spongiform encephalopathy with zoonotic potential and the risk of nosocomial and blood transfusion-related transmission. Active surveillance has been implemented in most European countries and requires important human resources and funding. Here, we studied whether national mortality and morbidity statistics can be used as reliable indicators. METHODS: CJD data collected by the French national CJD surveillance centre were compared with data registered in the national mortality statistics. RESULTS: From 2000 to 2008, the two sources reported fairly similar numbers of CJD deaths. However, analysis of individual data showed important between-sources disagreement. Nearly 24% of CJD reported by the mortality register were false positive diagnoses and 21.6% of the CJD cases diagnosed by the surveillance centre were not registered as CJD in the national mortality statistics. One out of 22 variant CJD cases was not reported as having any type of CJD in the mortality statistics. CONCLUSIONS: These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data. PMID- 22057089 TI - Human cytomegalovirus glycoprotein B genotypes in Chinese hematopoietic stem cell transplant recipients. AB - OBJECTIVES: To investigate the distribution of human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes and to explore the possible relationship between gB genotypes and clinical characteristics in Chinese hematopoietic stem cell transplant (HSCT) recipients. METHODS: A prospective analysis of gB genotypes was conducted on HCMV clinical isolates obtained from 102 HSCT recipients. Real-time quantitative PCR and PCR-based restriction fragment length polymorphism analysis were applied for the determination of viral loads and gB genotypes, respectively. RESULTS: The distribution of gB genotypes was as follows: gB1, 54/102 (52.9%); gB3, 21/102 (20.6%); and mixtures, 27/102 (26.5%). The rate of viral clearance at day 21 was higher in patients infected with the gB1 genotype than in those infected with the gB3 genotype (56 and 29%, respectively; p = 0.036). In contrast, the rate of HCMV reactivation/reinfection was higher in patients infected with the gB3 genotype than in those infected with the gB1 genotype (81 and 56%, respectively; p = 0.041). CONCLUSIONS: The HCMV gB1 genotype is the most prevalent among Chinese HSCT recipients; patients infected with the gB3 genotype have more difficulty eradicating the virus and have a higher risk of reactivation/reinfection than those infected with the gB1 genotype. PMID- 22057091 TI - Accurate on-line nu-support vector learning. AB - The nu-Support Vector Machine (nu-SVM) for classification proposed by Scholkopf et al. has the advantage of using a parameter nu on controlling the number of support vectors and margin errors. However, comparing to standard C-Support Vector Machine (C-SVM), its formulation is more complicated, up until now there are no effective methods on solving accurate on-line learning for it. In this paper, we propose a new effective accurate on-line algorithm which is designed based on a modified formulation of the original nu-SVM. The accurate on-line algorithm includes two special steps: the first one is relaxed adiabatic incremental adjustments; the second one is strict restoration adjustments. The experiments on several benchmark datasets demonstrate that using these two steps the accurate on-line algorithm can avoid the infeasible updating path as far as possible, and successfully converge to the optimal solution. It achieves the fast convergence especially on the Gaussian kernel and is faster than the batch algorithm. PMID- 22057092 TI - The maximum vector-angular margin classifier and its fast training on large datasets using a core vector machine. AB - Although pattern classification has been extensively studied in the past decades, how to effectively solve the corresponding training on large datasets is a problem that still requires particular attention. Many kernelized classification methods, such as SVM and SVDD, can be formulated as the corresponding quadratic programming (QP) problems, but computing the associated kernel matrices requires O(n2)(or even up to O(n3)) computational complexity, where n is the size of the training patterns, which heavily limits the applicability of these methods for large datasets. In this paper, a new classification method called the maximum vector-angular margin classifier (MAMC) is first proposed based on the vector angular margin to find an optimal vector c in the pattern feature space, and all the testing patterns can be classified in terms of the maximum vector-angular margin rho, between the vector c and all the training data points. Accordingly, it is proved that the kernelized MAMC can be equivalently formulated as the kernelized Minimum Enclosing Ball (MEB), which leads to a distinctive merit of MAMC, i.e., it has the flexibility of controlling the sum of support vectors like v-SVC and may be extended to a maximum vector-angular margin core vector machine (MAMCVM) by connecting the core vector machine (CVM) method with MAMC such that the corresponding fast training on large datasets can be effectively achieved. Experimental results on artificial and real datasets are provided to validate the power of the proposed methods. PMID- 22057093 TI - Fabrication of layered nanostructures by successive electron beam induced deposition with two precursors: protective capping of metallic iron structures. AB - We report on the stepwise generation of layered nanostructures via electron beam induced deposition (EBID) using organometallic precursor molecules in ultra-high vacuum (UHV). In a first step a metallic iron line structure was produced using iron pentacarbonyl; in a second step this nanostructure was then locally capped with a 2-3 nm thin titanium oxide-containing film fabricated from titanium tetraisopropoxide. The chemical composition of the deposited layers was analyzed by spatially resolved Auger electron spectroscopy. With spatially resolved x-ray absorption spectroscopy at the Fe L3 edge, it was demonstrated that the thin capping layer prevents the iron structure from oxidation upon exposure to air. PMID- 22057094 TI - The human relevant potency threshold: reducing uncertainty by human calibration of cumulative risk assessments. AB - The 2008 National Research Council report "Phthalates and Cumulative Risk Assessment: Tasks Ahead," rejected the underlying premises of TEQ-like approaches - e.g., chemicals are true congeners; are metabolized and detoxified similarly; produce the same biological effects by the same mode of action; exhibit parallel dose response curves - instead asserting that cumulative risk assessment should apply dose addition (DA) to all chemicals that produce "common adverse outcomes" (CAOS). Published mixtures data and a human health risk assessment for phthalates and anti-androgens were evaluated to determine how firmly the DA-CAOS concept is supported and with what level of statistical certainty the results may be extrapolated to lower doses in humans. Underlying assumptions of the DA-CAOS concept were tested for accuracy and consistency against data for two human pharmaceuticals and its logical predictions were compared to human clinical and epidemiological experience. Those analyses revealed that DA-CAOS is scientifically untenable. Therefore, an alternative approach was developed - the Human-Relevant Potency-Threshold (HRPT) - that appears to fit the data better and avoids the contradictions inherent in the DA-CAOS concept. The proposed approach recommends application of independent action for phthalates and other chemicals with potential anti-androgenic properties at current human exposure levels. PMID- 22057095 TI - Background incidence of liver chemistry abnormalities in pediatric clinical trials for conditions with and without underlying liver disease. AB - BACKGROUND: The FDA provides guidance regarding pre-marketing liver chemistry subject stopping criteria. This study was undertaken to determine the background rates of liver chemistry abnormalities in pediatric clinical trials for conditions with and without underlying liver disease (LD). METHODS: The study included 5410 subjects aged 0-18years in 24 trials for conditions without LD. 3756 pediatric subjects in 14 trials for conditions with LD (malaria, HIV, HBV) were also analyzed. Prevalence and incidence of abnormal liver chemistries were calculated. RESULTS: In conditions without LD, the overall incidence were 0.54 (95%CI 0.20-1.17) per 1000 person-months for ALT?3xULN, 0.36 (95%CI 0.10-0.92) for ALT?5xULN, and 0.27 (95%CI 0.06-0.78) for ALT?8xULN, 1.03 (95%CI 0.50-1.90) for ALP?2xULN, and 0.22 (95%CI 0.03-0.78) for combined ALT?3xULN and TBIL?2xULN. Incidence of ALT?3xULN (8.17 95%CI 6.42-10.24) were much higher in trials of conditions with LD. However, combined elevations of ALT?3xULN and TBIL?2xULN were only marginally higher 0.37 (95%CI 0.10-1.08). CONCLUSION: Elevations of ALT (3xULN) and TBIL (2xULN) are rare in pediatric trial populations for conditions without underlying liver disease and can be considered a safety signal. For trials in conditions with liver disease, the potential for drug-induced liver injury must be distinguished from underlying disease progression. PMID- 22057096 TI - Medication use and functional status decline in older adults: a narrative review. AB - BACKGROUND: Functional status is the cornerstone of geriatric care and serves as an indicator of general well-being. A decline in function can increase health care use, worsen quality of life, threaten independence, and increase the risk of mortality. One of several risk factors for decline in functional status is medication use. OBJECTIVE: Our aim was to critically review published articles that have examined the relationship between medication use and functional status decline in the elderly. METHODS: The MEDLINE and EMBASE databases were searched for English-language articles published from January 1986 to June 2011. Search terms included aged, humans, drug utilization, polypharmacy, inappropriate prescribing, anticholinergics, psychotropics, antihypertensives, drug burden index, functional status, function change or decline, activities of daily living, gait, mobility limitation, and disability. A manual search of the reference lists of the identified articles and the authors' article files, book chapters, and recent reviews was conducted to retrieve additional publications. Only articles that used rigorous observational or interventional designs were included. Cross sectional studies and case series were excluded from this review. RESULTS: Nineteen studies met the inclusion criteria. Five studies addressed the impact of suboptimal prescribing on function, 3 of which found an increased risk of worse function in community-dwelling subjects receiving polypharmacy. Three of the 4 studies that assessed benzodiazepine use and functional status decline found a statistically significant association. One cohort study identified no relationship between antidepressant use and functional status, whereas a randomized trial found that amitriptyline, but not desipramine or paroxetine, impaired certain measures of gait. Two studies found that increasing anticholinergic burden was associated with worse functional status. In a study of hospitalized rehabilitation patients, users of hypnotics/anxiolytics (eg, phenobarbital, zolpidem) had lower relative Functional Independence Measure motor gains than nonusers. Use of multiple central nervous system (CNS) drugs (using different definitions) was linked to greater declines in self-reported mobility and Short Physical Performance Battery (SPPB) scores in 2 community-based studies. Another study of nursing home patients did not report a significant decrease in SPPB scores in those taking multiple CNS drugs. Finally, 2 studies found mixed effects between antihypertensive use and functional status in the elderly. CONCLUSIONS: Benzodiazepines and anticholinergics have been consistently associated with impairments in functional status in the elderly. The relationships between suboptimal prescribing, antidepressants, and antihypertensives and functional status decline were mixed. Further research using established measures and methods is needed to better describe the impact of medication use on functional status in older adults. PMID- 22057097 TI - Engineering assessment of the longitudinal compression behaviour of contemporary coronary stents. AB - AIMS: There have been recently reported clinical observations of significant longitudinal compression or "stent shortening" in certain contemporary drug eluting stents (DES), when re-crossed with other devices such as post-dilatation balloons, stent delivery systems or intravascular ultrasound (IVUS) catheters. The aim of this study was to understand the effect of stent design on longitudinal compression for coronary stents, when subjected to certain forces in vitro. This goal was achieved by experimentally evaluating the longitudinal strength of 14 contemporary stent designs under a clinically relevant compression force using a bench test method developed for this purpose. The results from the study are intended to provide an indication whether there is a quantifiable difference in the ability of the different stent platform designs to resist longitudinal compression in a deployed configuration. METHODS AND RESULTS: A test method was developed to evaluate the longitudinal compression behaviour of coronary stents. The test method was used to compare the longitudinal compression of four stent design families including a total of 14 commercialised stent platforms under a clinically relevant longitudinal compression force. The nominal expansion diameter of stents used in this study was 3.0 mm with stent lengths ranging from 28-30 mm. A test method was also developed to estimate a value of the clinically relevant longitudinal compression force to which a deployed stent may be subjected in a situation when a catheter tip is caught while trying to cross a freshly deployed stent. That force was determined to be 50 gram force (gf) (0.49 N). Based on the results of the testing it was noted that three of the four design families (13 of the 14 stents tested) demonstrated a longitudinal compression in the range of 1.25-5.30 mm (longitudinal compression of 4.46% 18.93% compared to the nominal expanded stent length), with the exception of the offset peak-to-peak stent platform having results clearly outside of this grouping. The stent in the offset peak-to-peak design category (Element stent platform) had an average longitudinal compression of 13.20 mm (longitudinal compression of 47.07%), thus demonstrating a markedly lower resistance to longitudinal compression. CONCLUSIONS: Stent design is a primary driver determining the longitudinal compression behaviour of coronary stent platforms. The results of this study comparing the longitudinal compression performance of four different commercial stent design families indicate that the tendency of a deployed stent to undergo longitudinal compression is associated with the stent design concept. It was determined that the particular 2-link offset peak-to-peak design evaluated in this study had the lowest compression resistance compared to the other stent design families. PMID- 22057098 TI - Cerebral microbleeds predict impending intracranial hemorrhage in infective endocarditis. AB - BACKGROUND: Cerebral microbleeds (CMBs) detected by T2*-weighted MRI are a potential indicator of hypertension, microvascular disease and hemorrhagic stroke. An association between infective endocarditis (IE) and CMBs has been reported recently, but the clinical significance remains unclear. We hypothesized that CMBs in patients with IE are associated with vascular vulnerabilities such as mycotic aneurysm or pyogenic vasculitis. METHODS: We retrospectively reviewed 26 consecutive patients with definite IE who underwent T2*-weighted MRI and were admitted to 2 medical centers in Osaka, Japan, between January 2006 and June 2010. We examined the incidence of symptomatic intracranial hemorrhage (ICH) occurring after initial MRI examination and investigated the association between ICH, CMBs and other clinical characteristics. RESULTS: CMBs were identified in 14 patients (54%), and 72% of CMBs were found in the lobar region. Symptomatic ICH was observed in 8 patients (31%) during the 3-month follow-up period after initial MRI examination. In multiple logistic regression analyses, the presence of preceding ICH [odds ratio (OR) 40.0, 95% confidence interval (CI) 2.5-2,870] and the presence of CMBs (OR 34.0, 95% CI 1.3-17,300) were independent predictors of the development of ICH. Using cutoff values for CMBs of >=2 and >=3, the adjusted ORs for ICH increased (OR 42.1, 95% CI 1.9-24,300, and OR 70.1, 95% CI 2.5-105,000, respectively). CONCLUSIONS: In addition to prior ICH, the presence of CMBs was a strong predictor of impending ICH in patients with IE. CMBs might represent vascular vulnerability related to IE. PMID- 22057099 TI - A facile approach for the delivery of inorganic nanoparticles into the brain by passing through the blood-brain barrier (BBB). AB - This study provides an easy and simple method to obtain inorganic nanoparticles that can penetrate the blood-brain barrier, the heavily guarded system in the brain, via cross-linked serum albumin surface coatings. Their intact BBB permeability was confirmed in both in vitro and in vivo tests. PMID- 22057100 TI - Carbon nanotube coated snowman-like particles and their electro-responsive characteristics. AB - We report the fabrication of core-shell structured snowman-like microparticles coated with multi-walled carbon nanotubes and their electro-responsive electrorheological behavior under an applied electric field strength when dispersed in silicone oil. It is observed that they form a chain-like structure, possessing microfluidic potential applications with their solid-like property. PMID- 22057101 TI - ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation. AB - Wallerian degeneration is observed in many neurological disorders, and it is therefore important to elucidate the axonal degeneration mechanism to prevent, and further develop treatment for, such diseases. The ubiquitin-proteasome system (UPS) has been implicated in Wallerian degeneration, but the underlying molecular mechanism remains unclear. Here we show that ZNRF1, an E3 ligase, promotes Wallerian degeneration by targeting AKT to degrade through the UPS. AKT phosphorylates glycogen synthase kinase-3beta (GSK3B), and thereby inactivates it in axons. AKT overexpression significantly delays axonal degeneration. Overexpression of the active (non-phosphorylated) form of GSK3B induces CRMP2 phosphorylation, which is required for the microtubule reorganization observed in the degenerating axon. The inhibition of GSK3B and the overexpression of non phosphorylated CRMP2 both protected axons from Wallerian degeneration. These findings indicate that the ZNRF1-AKT-GSK3B-CRMP2 pathway plays an important role in controlling Wallerian degeneration. PMID- 22057102 TI - Torture in retrospect (1992-2000). PMID- 22057103 TI - Comparison of two methods of inquiry for torture with East African refugees: single query versus checklist. AB - PURPOSE: First to compare two methods of inquiry regarding torture: i.e., the traditional means of inquiry versus a checklist of torture experiences previously identified for these African refugees. Second, we hoped to identify factors that might influence refugees to not report torture on a single query when checklist data indicated torture events had occurred or to report torture when checklist data indicated that torture had not occurred. METHOD: Consisted of queries to 1,134 community-dwelling East African refugees (Somalia and Ethiopia) regarding the presence-versus-absence of torture in Africa (single query), a checklist of torture experiences in Africa that we had previously identified as occurring in these groups, demography, non-torture traumatic experiences in Africa, and current posttraumatic symptoms. RESULTS: Showed that 14% of the study participants reported a torture experience on a checklist, but not on a single query. Nine percent responded positively to the single query on torture, but then failed to check any torture experience. Those reporting trauma on an open-ended query, but not on a checklist, had been highly traumatized in other ways (warfare, civil chaos, robbery, assault, rape, trauma during flight out of the country). Those who reported torture on the checklist but not on the single query reported fewer instances of torture, suggesting that perhaps a "threshold" of torture experience influenced the single-query report. In addition, certain types of torture appeared more apt to be associated with a singlequery endorsement of torture. On regression analysis, a single-query self-report of torture was associated with traumatic experiences consistent with torture, older age, female gender, and nontorture trauma in Africa. CONCLUSION: Inconsistent reporting of torture occurred when two methods of inquiry (one openended and one a checklist) were employed in this sample. We believe that specific contexts of torture and non-torture trauma, together with individual demographic characteristics and severity of the trauma, affect the self-perception of having been tortured. Specific information regarding these contexts, demographic characteristics, and trauma severity are presented in the report. PMID- 22057104 TI - How to combat torture if perpetrators are supported by a religious "justification". AB - While there are some examples of legal cases which have resulted in the prosecution of perpetrators and successful reparation for survivors, in countries such as Iran such due procedure is close to impossible since torture is practiced by state officials mostly based on religious codes, and the legal system is controlled by practices that makes it close to impossible to achieve justice. This article discusses the implications of such a situation that also include health care professionals in third party countries who have an obligation to document evidence using the Istanbul Protocol based on a case example of a survivor exposed to different forms of torture. PMID- 22057105 TI - Near-death experience and out of body phenomenon during torture--a case report. AB - A case of a near death experience (NDE) associated with an "Out of body" phenomenon in an African man as a result of torture is presented. Although NDEs occur in approximately ten per cent of survivors of cardiac arrest, case reports emerging from the medical examination of torture victims are lacking. This may be due to cultural/linguistic barriers and fear of disbelief. Low NDE incidence during torture would suggest that torture techniques rarely induce the critical brain ischaemia considered necessary to provoke an NDE. Alternatively psychological or physical characteristics of torture may render NDE harder to recall. Proof of low incidence during torture would counter the theory that NDEs are a psychological response to perceived threat of death. NDEs often induce transformational benefits in patients' lives and for this reason the author urges physicians to consider the possibility of NDE amongst torture victims under their care. A request for information about similar cases is made. PMID- 22057106 TI - Intercultural encounters in counselling and psychotherapy--communication with the help of interpreters. AB - Treatment and rehabilitation of torture victims and persons traumatized by war or persecution can require working in an intercultural setting, as is the case when working with refugees and migrants. The following article offers practical advice for diagnostics, counselling and treatment of patients from other cultures who are not speaking the language of the therapist. PMID- 22057107 TI - Statement on hooding. PMID- 22057109 TI - Contributory torture. PMID- 22057110 TI - Torture documentation inside detention centres. PMID- 22057111 TI - Osteological proofs of torture and cruelty: forensic findings form a secret cemetery in Tirana, Albania. AB - Two decades after the fall of the communism in Albania, documenting the human rights violations and proving torture and cruelties suffered from ex-politically persecuted and dissidents of the regime, is still a societal priority. Due to several reasons, the judicial way toward redressing the historical injustices has been slowed down. This is mainly because of the lack of proper documentation of torture, mass executions and extrajudicial ill-treatment. Several governmental and civil society organizations have tried to define the issue, but perpetrators have rarely, if ever, been brought to court. Secret cemeteries and mass graves have recently been found in different zones of Albania, and victims exhumed; thus proofs of torture and ill-treatments are being made widely known, potentially creating the necessary legal conditions for punishing the perpetrators and for identifying victims. In the present paper, authors describe osteological forensic findings from Linza secret cemetery in Tirana, where several ante mortem fractures prove the severe and cruel ill-treatment the victims suffered before the execution that was usually by bullet shot in the posterior region of the skull. PMID- 22057112 TI - CCL17 promotes intestinal inflammation in mice and counteracts regulatory T cell mediated protection from colitis. AB - BACKGROUND & AIMS: Priming of T cells by dendritic cells (DCs) in the intestinal mucosa and associated lymphoid tissues helps maintain mucosal tolerance but also contributes to the development of chronic intestinal inflammation. Chemokines regulate the intestinal immune response and can contribute to pathogenesis of inflammatory bowel diseases. We investigated the role of the chemokine CCL17, which is expressed by conventional DCs in the intestine and is up-regulated during colitis. METHODS: Colitis was induced by administration of dextran sodium sulfate (DSS) to mice or transfer of T cells to lymphopenic mice. Colitis activity was monitored by body weight assessment, histologic scoring, and cytokine profile analysis. The direct effects of CCL17 on DCs and the indirect effects on differentiation of T helper (Th) cells were determined in vitro and ex vivo. RESULTS: Mice that lacked CCL17 (Ccl17(E/E) mice) were protected from induction of severe colitis by DSS or T-cell transfer. Colonic mucosa and mesenteric lymph nodes from Ccl17-deficient mice produced lower levels of proinflammatory cytokines. The population of Foxp3(+) regulatory T cells (Tregs) was expanded in Ccl17(E/E) mice and required for long-term protection from colitis. CCR4 expression by transferred T cells was not required for induction of colitis, but CCR4 expression by the recipients was required. CCL17 promoted Toll like receptor-induced secretion of interleukin-12 and interleukin-23 by DCs in an autocrine manner, promoted differentiation of Th1 and Th17 cells, and reduced induction of Foxp3(+) Treg cells. CONCLUSIONS: The chemokine CCL17 is required for induction of intestinal inflammation in mice. CCL17 has an autocrine effect on DCs that promotes production of inflammatory cytokines and activation of Th1 and Th17 cells and reduces expansion of Treg cells. PMID- 22057113 TI - dysregulation of CD1d-restricted type ii natural killer T cells leads to spontaneous development of colitis in mice. AB - BACKGROUND & AIMS: CD1d-restricted natural killer (NK) T cells are a subset of immunoregulatory T cells that comprise type I (express the semi-invariant T-cell receptor [TCR] and can be detected using the alpha-galactosylceramide/CD1d tetramer) and type II (express diverse TCRs and cannot be directly identified). Studies in mouse models of inflammatory bowel disease revealed a complex role for type I NKT cells in the development of colitis. Type II NKT cells have been associated with intestinal inflammation in patients with ulcerative colitis. METHODS: To investigate whether dysregulation of type II NKT cells, caused by increased expression of CD1d, can contribute to colitis, we generated transgenic mice that express high levels of CD1d and a TCR from an autoreactive, type II NKT cell (CD1dTg/24alphabetaTg mice). RESULTS: CD1dTg/24alphabetaTg mice had reduced numbers of 24alphabeta T cells compared with 24alphabetaTg mice, indicating that negative selection increases among type II NKT cells engaged by abundant self antigen. The residual 24alphabeta T cells in CD1dTg/24alphabetaTg mice had an altered surface phenotype and acquired a cytokine profile distinct from that of equivalent cells in 24alphabetaTg mice. Interestingly, CD1dTg/24alphabetaTg mice spontaneously developed colitis; adoptive transfer experiments confirmed that type II NKT cells that develop in the context of increased CD1d expression are pathogenic. CONCLUSIONS: Aberrant type II NKT cell responses directly contribute to intestinal inflammation in mice, indicating the importance of CD1d expression levels in the development and regulation of type II NKT cells. PMID- 22057114 TI - Frequent aneuploidy among normal human hepatocytes. AB - Murine hepatocytes become polyploid and then undergo ploidy reversal and become aneuploid in a dynamic process called the ploidy conveyor. Although polyploidization occurs in some types of human cells, the degree of aneuploidy in human hepatocytes is not known. We isolated hepatocytes derived from healthy human liver samples and determined chromosome number and identity using traditional karyotyping and fluorescence in situ hybridization. Similar to murine hepatocytes, human hepatocytes are highly aneuploid. Moreover, imaging studies revealed multipolar spindles and chromosome segregation defects in dividing human hepatocytes. Aneuploidy therefore does not necessarily predispose liver cells to transformation but might promote genetic diversity among hepatocytes. PMID- 22057115 TI - Selective activation of nuclear bile acid receptor FXR in the intestine protects mice against cholestasis. AB - BACKGROUND & AIMS: Cholestasis is a liver disorder characterized by impaired bile flow, reduction of bile acids (BAs) in the intestine, and retention of BAs in the liver. The farnesoid X receptor (FXR) is the transcriptional regulator of BA homeostasis. Activation of FXR by BAs reduces circulating BA levels in a feedback mechanism, repressing hepatic cholesterol 7alpha-hydroxylase (Cyp7a1), the rate limiting enzyme for the conversion of cholesterol to BAs. This mechanism involves the hepatic nuclear receptor small heterodimer partner and the intestinal fibroblast growth factor (FGF) 19 and 15. We investigated the role of activation of intestine-specific FXR in reducing hepatic levels of BAs and protecting the liver from cholestasis in mice. METHODS: We generated transgenic mice that express a constitutively active FXR in the intestine. Using FXR gain- and loss-of function models, we studied the roles of intestinal FXR in mice with intrahepatic and extrahepatic cholestasis. RESULTS: Selective activation of intestinal FXR induced FGF15 and repressed hepatic Cyp7a1, reducing the pool size of BAs and changing the BA pool composition. Activation of intestinal FXR protected mice from obstructive extrahepatic cholestasis after bile duct ligation or administration of alpha-naphthylisothiocyanate. In Mdr2(-/-) mice, transgenic expression of activated FXR in the intestine protected against liver damage, whereas absence of FXR promoted progression of liver disease. CONCLUSIONS: Activation of FXR transcription in the intestine protects the liver from cholestasis in mice by inducing FGF15 expression and reducing the hepatic pool of BA; this approach might be developed to reverse cholestasis in patients. PMID- 22057116 TI - [Comprehensive Care Center Bonn from 1980 to 2009. Changes in the epidemiology and regional composition of the haemophilia population]. AB - The Bonn Haemophilia Care Center provides patient care on a superregional level. The centre's large service area is, in part, due to the introduction of haemophilia home treatment and related to this the individualized prophylaxis in children and adults by Egli and Brackmann in Bonn in the early 1970s, that represented a milestone in German haemophilia therapy. Epidemiologic patient data from the two selected time points, 1980 and 2009, are evaluated to illustrate the change in the composition of the patient clientele. In 1980 a total of 639 patients were treated at the Bonn Haemophilia Center. 529 patients exhibited a severe form and 110 a non-severe form of the respective clotting disorder. In 2009 the Bonn Haemophilia Center took care for a total of 837 patients. There were 445 patients who suffered from a severe form of the considered clotting disorder while 392 showed a non-severe course. The number of less severely affected patients has increased significantly in 2009. Patients in 1980 were predominantly suffering from a severe form and most had to travel more than 150 km from their homes to the treatment center. In 2009 the number of patients living a medium-long distance from the care provider has significantly increased while the number of patients living more than 150 km from the center has decreased. Comparing 2009 to 1980 a growth of the center's regional character becomes apparent, especially when patient age and severity of the coagulation disorder are taken into consideration. The regional character was more strongly pronounced with milder disease severity and lower patient age. Due to the existence of well established primary haemophilia care in CCCs in Germany, the trend for the recent years is that the proportion of young patients that choose haemophilia care providers closer to their homes is increasing. PMID- 22057117 TI - Evolution of the TOR pathway. AB - The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and provide a practical framework on which experimental evidence can be compared between species. Here we performed phylogenetic analyses on the components of the TOR pathway and determined their point of invention. We find that the two TOR complexes and a large part of the TOR pathway originated before the Last Eukaryotic Common Ancestor and form a core to which new inputs have been added during animal evolution. In addition, we provide insight into how duplications and sub functionalization of the S6K, RSK, SGK and PKB kinases shaped the complexity of the TOR pathway. In yeast we identify novel AGC kinases that are orthologous to the S6 kinase. These results demonstrate how a vital signaling pathway can be both highly conserved and flexible in eukaryotes. PMID- 22057118 TI - Mapping QTL controlling maize deep-seeding tolerance-related traits and confirmation of a major QTL for mesocotyl length. AB - Deep-seeding tolerant seeds can emerge from deep soil where the moisture is suitable for seed germination. Breeding deep-seeding tolerant cultivars is becoming increasingly important in arid and semi-arid regions. To dissect the quantitative trait loci (QTL) controlling deep-seeding tolerance traits, we selected a tolerant maize inbred line 3681-4 and crossed it with the elite inbred line-X178 to generate an F(2) population and the derivative F(2:3) families. A molecular linkage map composed of 179 molecular markers was constructed, and 25 QTL were detected including 10 QTL for sowing at 10 cm depth and 15 QTL for sowing at 20 cm depth. The QTL analysis results confirmed that deep-seeding tolerance was mainly caused by mesocotyl elongation and also revealed considerable overlap among QTL for different traits. To confirm a major QTL on chromosome 10 for mesocotyl length measured at 20 cm depth, we selected and self pollinated a BC(3)F(2) plant that was heterozygous at the markers around the target QTL and homozygous at other QTL to generate a BC(3)F(3) population. We found that this QTL explained more phenotypic variance in the BC(3)F(3) population than that in the F(2) population, which laid the foundation for fine mapping and NIL (near-isogenic line) construction. PMID- 22057119 TI - Cloning and expression analysis of the transforming growth factor-beta receptors type 1 and 2 in the rainbow trout Oncorhynchus mykiss. AB - Transforming growth factor-beta (TGF-beta) binding to the TGF-beta type I (TGFBR1) and type II (TGFBR2) receptors delivers a plethora of cell-type specific effects. Moreover, the responses to TGF-beta are tuned by regulatory mechanisms at the receptor level itself. To further elucidate TGF-beta family signal transduction in teleosts, we therefore cloned the first complete set of a putative TGF-beta receptor complex in salmonids. Rainbow trout TGFBR1 and TGFBR2 are transmembrane proteins with a serine/threonine kinase domain and are highly conserved within vertebrates. High expression levels in muscle and brain indicate regulation of the TGF-beta system in muscular and nervous systems. Lipopolysaccharide (LPS) induced expression of both receptor chains in RTgill cells while bacterial and viral mimics modulated the two receptors inversely in head kidney (HK) macrophages. In addition, T cell mitogens lowered receptor levels in HK leukocytes. These data provide the first insights into TGF-beta type I and II receptor modulation during immune responses in teleost fish. PMID- 22057120 TI - Malignant sinonasal papilloma with neck metastasis: a rare report and literature review. AB - Sinonasal papillomas are relatively rare, benign epithelial tumours of the nasal cavity. These lesions generate considerable interest because they are locally aggressive, have a tendency to recur and are associated with malignancy. The authors present a unique case of malignant sinonasal papilloma with neck metastasis. In the English literature only one case of such a presentation has been reported. PMID- 22057121 TI - Evaluation of postoperative function in patients undergoing reconstruction following resection of superior and lateral oropharyngeal cancer: long-term outcomes of reconstruction with the Gehanno method. AB - Resection of the superior or lateral wall of the cancer-affected oropharynx can often lead to disturbed nasal breathing, dysphagia, and dysarthria. The authors used the Gehanno method to reconstruct these surgical defects and achieved favourable functional recovery soon after surgery. The present study was undertaken to analyze the long-term outcome and usefulness of this method. Reconstruction was carried out using the Gehanno method in 36 patients during the 10-year period between 1997 and 2007. Both short-term and long-term evaluations of the postoperative function were performed in 12 of the 36 cases. The postoperative function was favourably maintained in all 12 cases, but gradual deterioration was noted in some cases in which the forearm flap had been used for reconstruction. Conventionally, the forearm flap is considered suitable for the reconstruction of complex structures such as the oropharynx because of its excellent flexibility. The results suggest that if the forearm flap is used for reconstruction using the Gehanno method, the surrounding tissue is likely to undergo change over time. The rectus abdominis myocutaneous flap should be considered as the first-choice flap for reconstruction using the Gehanno method. PMID- 22057122 TI - Mandibular central mucoepidermoid carcinoma with distant metastasis. AB - Mucoepidermoid carcinoma is the most common malignant salivary gland tumour. Central mucoepidermoid carcinomas (CMC) are an exceedingly rare subgroup, representing 2-4% of all cases. The authors report on a case of CMC in a patient who presented with trigeminal neuropathy, trismus and distant metastasis. The possible pathogenesis of CMC and criteria for diagnosis are discussed. PMID- 22057123 TI - Adipokines and cardiovascular risk in Cushing's syndrome. AB - Cushing's syndrome (CS) is associated with increased cardiovascular morbidity and mortality. Recent evidence also suggests that increased cardiovascular risk may persist even after long-term remission of CS. Increased central obesity, a typical feature of CS, is associated with altered production of adipokines, which contributes to the pathogenesis of several metabolic and cardiovascular complications observed in this condition. In vitro and in vivo studies have shown a relationship between cortisol and adipokines in several experimental settings. In patients with either active or 'cured' CS, an increase in leptin and resistin levels as well as the release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6, may be associated with increased cardiovascular risk. For other adipokines, including adiponectin, results are inconclusive. Studies are needed to further elucidate the interactions between clinical and subclinical increases in cortisol production and altered adipokine release in CS. PMID- 22057124 TI - Prolonged survival of patients with metastatic colorectal cancer following first line oxaliplatin-based chemotherapy with molecular targeting agents and curative surgery. AB - BACKGROUND: The ability of molecular targeting agents to improve overall survival (OS) in metastatic colorectal cancer (MCRC) patients who underwent oxaliplatin based chemotherapy remains controversial. METHODS: We retrospectively analyzed 331 patients with MCRC who underwent first-line oxaliplatin-based chemotherapy. Treatment outcomes were compared between patients who started chemotherapy from April 2005 to March 2007 (cohort A; n = 157) and those who started it from April 2007 to March 2009 (cohort B; n = 174). To evaluate the impact of exposure to agents, we applied time-varying covariate analysis to avoid possible lead-time bias. RESULTS: Median OS of cohorts A and B was 21.3 and 28.6 months, respectively (HR 0.66, 95% CI 0.50-0.87, p = 0.003). Exposure to bevacizumab (25 vs. 76%), anti-epidermal growth factor receptor (EGFR) (18 vs. 33%) or curative surgery after chemotherapy (4 vs. 10%) was significantly higher in cohort B. According to a multivariate Cox model with exposure to each agent or treatment as a time-varying covariate, hazard ratios of death were 0.71 (95% CI, 0.51-0.96; p = 0.03) for bevacizumab, 0.62 (95% CI, 0.40-0.89; p = 0.01) for anti-EGFR and 0.22 (95% CI, 0.06-0.57; p = 0.004) for surgery. CONCLUSIONS: Increased exposure to molecular targeting agents or surgery after chemotherapy appears to contribute to an improvement in OS in recent patients with MCRC who have undergone oxaliplatin-based chemotherapy. PMID- 22057125 TI - Coronary stent longitudinal deformation by compression: is this a new global stent failure, a specific failure of a particular stent design or simply an angiographic detection of an exceptional PCI complication? PMID- 22057126 TI - Structural basis of p38alpha regulation by hematopoietic tyrosine phosphatase. AB - MAP kinases regulate essential cellular events, including cell growth, differentiation and inflammation. The solution structure of a complete MAPK-MAPK regulatory protein complex, p38alpha-HePTP, was determined, enabling a comprehensive investigation of the molecular basis of specificity and fidelity in MAPK regulation. Structure determination was achieved by combining NMR spectroscopy and small-angle X-ray scattering data with a new ensemble calculation-refinement procedure. We identified 25 residues outside of the HePTP kinase interaction motif necessary for p38alpha recognition. The complex adopts an extended conformation in solution and rarely samples the conformation necessary for kinase deactivation. Complex formation also does not affect the N terminal lobe, the activation loop of p38alpha or the catalytic domain of HePTP. Together, these results show how the downstream tyrosine phosphatase HePTP regulates p38alpha and provide for fundamentally new insights into MAPK regulation and specificity. PMID- 22057127 TI - Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans. AB - The DAF-9 cytochrome P450 is a key regulator of dauer formation, developmental timing and longevity in the nematode Caenorhabditis elegans. Here we describe the first identified chemical inhibitor of DAF-9 and the first reported small molecule tool that robustly induces dauer formation in typical culture conditions. This molecule (called dafadine) also inhibits the mammalian ortholog of DAF-9(CYP27A1), suggesting that dafadine can be used to interrogate developmental control and longevity in other animals. PMID- 22057128 TI - Ratiometric fluorescence imaging for distinguishing chloride concentration between normal and ischemic ventricular myocytes. AB - We devised a new ratiometric fluorescent probe for the detection of chloride ions. This synthesized probe was applied to the ventricular myocytes to successfully realize dynamic imaging of Cl(-) concentration fluctuations during the myocardial ischemia course. PMID- 22057129 TI - Coordination-driven self-assembly of polyoxometalates into discrete supramolecular triangles. AB - Pd(II)-directed self-assembly of a 3-pyridyl grafted Lindqvist hexavanadate led to the formation of a unique trimeric species, as confirmed by a variety of techniques, including pulsed-field gradient NMR spectroscopy and high-resolution ESI mass spectrometry. PMID- 22057130 TI - Enhanced antibacterial activity of bimetallic gold-silver core-shell nanoparticles at low silver concentration. AB - Herein we report the development of bimetallic Au@Ag core-shell nanoparticles (NPs) where gold nanoparticles (Au NPs) served as the seeds for continuous deposition of silver atoms on its surface. The core-shell structure and morphology were examined by UV-Vis spectroscopy, transmission electron microscopy (TEM), energy dispersive X-ray (EDX) analysis and X-ray diffraction (XRD). The core-shell NPs showed antibacterial activity against both gram negative (Escherichia coli and Pseudomonas aeruginosa) and gram positive (Enterococcus faecalis and Pediococcus acidilactici) bacteria at low concentration of silver present in the shell, with more efficacy against gram negative bacteria. TEM and flow cytometric studies showed that the core-shell NPs attached to the bacterial surface and caused membrane damage leading to cell death. The enhanced antibacterial properties of Au@Ag core-shell NPs was possibly due to the more active silver atoms in the shell surrounding gold core due to high surface free energy of the surface Ag atoms owing to shell thinness in the bimetallic NP structure. PMID- 22057131 TI - Contribution of cystatin C gene polymorphisms to cerebral white matter lesions. AB - BACKGROUND: Vascular remodeling plays an important role in the development of arteriosclerosis and any of the resulting white matter lesions in the brain. An imbalance between cysteine proteases and the cysteine protease inhibitor cystatin C (CST3) may exacerbate vascular remodeling through degradation of extracellular matrix proteins. Therefore, we evaluated the association between functional polymorphisms in the CST3 gene and the development of cerebral white matter lesions. METHODS: In a total of 2,676 participants, 3 CST3 genepolymorphisms were genotyped in 92 cases with severe deep white matter hyperintensity (DWMH), and 184 subjects were randomly selected age- and sex-matched controls without any signs of DWMH. The genetic effects of these polymorphisms on DWMH and plasma CST3 levels were examined. CST3 expression vectors were transfected into an astrocytoma cell line and the expression level of CST3 mRNA was analyzed by quantitative RT-PCR. Intracellular and secreted levels of CST3 in the cell culture were quantified by Western blot and ELISA, respectively. RESULTS: A significant association was found between one CST3 gene haplotype and DWMH (p = 0.002). This haplotype was also associated with lower plasma CST3 levels (p = 0.01). An in vitro transfection study revealed that the +148A allele, which is included in the risk haplotype, significantly reduced the secretion and increased the intracellular accumulation of CST3; however, it had no effect on the mRNA expression. CONCLUSIONS: Our study shows that polymorphisms in the CST3 gene are significantly associated with the likelihood of DWMH. Substitution of A for G at +148 of the CST3 gene decreased the extracellular availability of CST3 in vitro, which might result in the activation of protease activity. PMID- 22057133 TI - Wire-shaped quantum dots-sensitized solar cells based on nanosheets and nanowires. AB - Wire-shaped quantum dots-sensitized solar cells (WS-QDSCs) based on nanosheets and nanowires were fabricated and investigated for this paper. The nanosheets grown on stainless steel (SS) wire by electrodeposition were mainly composed of Zn5(OH)8Cl2.H2O and most of the Zn5(OH)8Cl2.H2O was converted to ZnO by post treatment, and ZnO nanowires were directly grown on SS wire by the hydrothermal method. CdS QDs were deposited on nanosheets and nanowires by successive ionic layer adsorption and reaction method. The results of photoelectrochemical performance indicated that WS-QDSCs showed a similar conversion efficiency in polysulfide and Na2SO4 electrolytes, while the WS-QDSCs based on the Cu2S counter electrode achieved much higher performance than those based on SS and Cu counter electrodes. By optimizing electrodeposition duration, the WS-QDSCs based on nanosheets presented the highest conversion efficiency of 0.60% for the duration of 20 min. Performance comparison indicated that the WS-QDSC based on nanosheets showed very superior performance to that based on the nanowires with similar film thickness. PMID- 22057134 TI - Ibandronate for prevention and treatment of glucocorticoid-induced osteoporosis in rabbits. AB - The objective of this study is to evaluate the efficacy of ibandronate (IBN) in prevention and treatment of glucocorticoid-induced osteoporosis in rabbits. A total of 60 New Zealand white rabbits were randomly allocated into six groups. Twenty rabbits in the control group were injected with saline. Forty rabbits received dexamethasone (DX) treatment at a dose of 3 mg/kg twice weekly during the first 6 weeks, while 10 of these rabbits (group IBN&DX) were injected additionally with IBN at a dose of 2 mg/kg before DX treatment. At week 6, the rabbits from IBN&DX group, 10 rabbits from control group (group CNTR-1) and 10 rabbits treated with DX (group DX6) were killed. Half (10) of the remaining rabbits in DX group were continued for DX treatment at a dose of 3 mg/kg once weekly (group DX12), while the other half (10) rabbits (group DX&IBN) additionally received IBN injection (2 mg/kg) once before continuing DX treatment. The remaining rabbits (10) in an additional of control group (group CNTR-2) continuously received saline. At week 12, all rabbits were killed for bone biomechanical analysis and histological examination. At week 6, the analysis of bone biomechanical and histological results of group CNTR-1 and DX6 showed that GIOP rabbit models were successfully established. Compared with group DX6, bone volume/tissue volume (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th) of lumbar spine in group IBN&DX were increased by 100, 45.74 and 40.55%, respectively (P < 0.01). Meanwhile, BV/TV and Tb.N of femoral neck were increased by 30.29 and 16.86%, respectively (P < 0.01). The maximum compressive load, the maximum bending stress and the maximum torque were increased by 24.19, 29.91 and 37.24%, respectively (P < 0.01). At week 12, in comparison of the results between group DX12 and group DX6, the histomorphometric and mechanical analysis demonstrated that prolonged DX treatment could lead to further loss of bone mass and strength. Compared with group DX12, BV/TV, Tb.N and Tb.Th of lumbar spine in group DX&IBN were increased by 73.34, 39.02 and 23.87%, respectively (P < 0.05), the parameters of femoral neck were increased by 88.75, 31.29 and 42.01%, respectively (P < 0.01), and the biomechanical parameters were increased by 54.36, 21.38 and 105.75%, respectively (P < 0.05). IBN could effectively prevent and treat high-dosing glucocorticoid-induced loss of bone mass and strength in rabbits. PMID- 22057135 TI - Performance of ultrasounds compared with radiographs to detect chronic enthesitis signs in patients with ankylosing spondylitis. AB - To assess the performance of ultrasound in detecting erosion, swelling, and new bone comparing to radiographs in five lower limb entheses in patients with ankylosing spondylitis (AS). Prospective study of 60 patients meeting modified New York criteria for AS. Lateral radiographs of both knees and ankles followed by a high-resolution Doppler ultrasound examination with a high-frequency (15 MHz) linear probe were performed. Ultrasound had an excellent sensitivity, but specificity was very weak compared to radiographs for erosion, swelling, and new bone formation. Negative and positive predictive values were good only for erosion. Ultrasound seems to be a performant instrument in detecting signs of chronic enthesitis particularly when radiograph is normal. PMID- 22057136 TI - Osteoprotegerin and RANKL in the pathogenesis of rheumatoid arthritis-induced osteoporosis. AB - Osteoporosis represents an important cause of morbidity in adult rheumatoid arthritis (RA) patients who exhibit increased fracture risk. It is thought that osteoclast and its dysfunction which mediated by many cytokines are the principal pathogenesis of this bone disease, although the mechanisms are still not fully understood. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) have been revealed in the pathogenesis of primary osteoporosis and other metabolic bone diseases. Thus, the aim of this study was to investigate the possible role of the OPG/RANKL system in RA-related bone loss. A total of 64 Chinese patients with RA and 60 healthy control subjects were involved. Serum levels of OPG and RANKL were measured by ELISA. BMD of nondominant forearm, lumbar spine(L(1-4)) and proximal femur, including femoral neck, Wards triangle, greater trochanter were assessed using dual-energy X-ray absorptiometry. RA patients had a higher incidence of osteoporosis (23/64, 35.9%) than that in healthy controls (9/60, 15.0%) (P < 0.0001). They displayed lower BMD values than controls at positions of all detected region. Compared with healthy controls, RA group showed significantly higher serum levels of RANKL (48.4 +/- 12.5 vs. 23.0 +/- 11.2 pmol/l, P < 0.0001), lower serum levels of OPG (106.2 +/- 40.6 vs. 231.6 +/- 65.6 pg/ml, P < 0.0001), and OPG/RANKL ratio (2.4 +/- 0.7 vs. 7.0 +/- 1.1, P < 0.0001). Multiple linear regression analysis revealed that in RA group, plasma rheumatoid factor concentration (beta = -0.187, P = 0.031), swollen joint count (beta = 0.567, P = 0.029), BMD at forearm (beta = 0.324, P = 0.002), femoral Wards triangle (beta = 0.370, P < 0.0001), and lumbar spine (beta = 0.313, P = 0.003) were the contributors for serum OPG (R ( 2 ) = 0.718, P < 0.0001). Age (beta = 0.241, P = 0.042) and BMD at femoral Wards triangle (beta = -0.441, P < 0.0001) and lumbar spine (beta = -0.320, P = 0.013) were the determinants for serum RANKL (R ( 2 ) = 0.616, P < 0.0001), while swollen joint count (beta = 1.029, P = 0.019) and BMD at femoral neck (beta = 0.285, P = 0.042) for serum OPG/RANKL ratio (R ( 2 ) = 0.279, P < 0.011). Analysis of logistic regression showed age (P = 0.004, OR = 1.156, 95% CI: 1.047-1.276) and the level of C reactive protein (P = 0.028, OR = 1.019, CI 95%: 1.002-1.036) in peripheral blood of RA were the risk factors for the occurrence of osteoporosis in RA, while OPG/RANKL ratio (P = 0.007, OR = 0.035, CI 95%: 0.003-0.400) was the unique protective factor. These data suggest that, in Chinese RA patients, an altered modulation of the OPG/RANKL system resulting in increased RANKL and decreased OPG in peripheral blood, could contribute to the bone loss characteristic and the generation of osteoporosis in these patients. Changes of ratio of OPG/RANKL might be a protective mechanism against the accelerated bone loss in RA. PMID- 22057137 TI - Is there a real adrenal axis dysfunction in patients with amyloidosis associated with familial Mediterranean fever? AB - Systemic amyloidosis with AA-type amyloid deposition is the major complication of FMF, leading to end stage renal disease. There is no clear data on the prevalence of adrenal involvement in patients with FMF amyloidosis. The aim of this study is to determine the adrenal axis function in patients FMF with amyloidosis. Twenty patients with FMF with amyloidosis (F/M: 10/10, mean age; 38 +/- 11 SD years), twenty without amyloidosis (F/M: 14/6, mean age 32 +/- 10 years), and healthy controls (F/M: 12/8, mean age: 30 +/- 7.6 SD years) were recruited. A dose of 250 mg tetracosactide (Synacthen) was then administered intravenously and further blood samples collected 30 and 60 min later. Blood samples were separated and collected at 4 degrees C, and serum cortisol levels were measured. A normal cortisol response to Synacthen was defined as a post-stimulation peak cortisol value of >18 mg/d either at 30 or 60 min. sample. The mean disease duration was 8.8 +/- 6 SD years, (range, 2-21) in FMF patients without amyloidosis compared to 16 +/- 9.5 years (range, 0-30) in FMF with amyloidosis (P = 0.001). The cortisol concentrations increased significantly at 30 and 60 min compared to baseline after injection of synacthen in all groups. There were no statistically significant differences found among three groups, for basal, 30 and 60 min for cortisol levels (P = 0.154). FMF patients with amyloidosis do not exhibit overt adrenal insufficiency even though their basal cortisol levels were mildly lower. PMID- 22057138 TI - Increased finger skin vasoreactivity and stimulated vasomotion associated with simvastatin therapy in systemic sclerosis hypercholesterolemic patients. AB - We conducted an open-label trial to evaluate whether simvastatin therapy was, or was not, associated in systemic sclerosis hypercholesterolemic patients (SSc-Ps) with beneficial changes in finger skin microvascular function. 13 females SSc-Ps and 15 females healthy control subjects (CSs), age-matched with SSc-Ps, underwent finger skin post-occlusive reactive hyperaemia (PORH), using laser Doppler flowmetry (LDF). This test was repeated in SSc-Ps after about 10 weeks of simvastatin (20 mg/day) therapy (ST). At baseline and after ST, finger skin vasomotion was evaluated using spectral Fourier analysis of the LDF tracings. Endothelin-1 and cholesterol serum levels were also determined in SSc-Ps at baseline and after ST. At baseline, SSc-Ps had significantly lower basal finger skin blood flow (basal flow) and PORH, compared to CSs (18.9 +/- 11.7 PU vs. 28.5 +/- 17.5 PU, 58.6 +/- 31.0 PU vs. 93. 1 +/- 37.3; P < 0.05). After ST, SSc-Ps had a significant increase in basal flow and PORH compared to baseline (42.7 +/- 35.7 PU vs. 18.9 +/- 11.7 PU, 111.0 +/- 66.6 PU vs. 58.6 +/- 31.0 PU, respectively; P < 0.05), as well as a significant reduction in endothelin-1, total- and LDL cholesterol serum levels. After ST, SSc-Ps also showed a partially restored post ischaemic amplification in finger skin blood flow oscillations within 0.06-0.6 Hz, related to myogenic vasomotion. This study showed that a short time period of ST in hypercholesterolemic SSc-Ps resulted in increased finger skin vasoreactivity and in partially restored post-ischaemic amplification of finger skin vasomotion, suggesting that ST affects positively finger skin microvascular dysfunction in SSc-Ps. PMID- 22057139 TI - A haplotype derived from the common variants at the -1997G/T and Sp1 binding site of the COL1A1 gene influences risk of postmenopausal osteoporosis in India. AB - The aim of the present study was to investigate the association between Collagen 1 alpha 1 (COL1A1) polymorphism and osteoporosis in DEXA verified 349 (145 osteoporotic, 87 osteopenic and 117 normal) postmenopausal women of India, who were not taking hormone replacement therapy. Two single-nucleotide polymorphisms (SNPs), that is, -1997G/T (rs1107946) and +1245G/T (rs1800012, Sp1) of the COL1A1 gene, were analyzed. Minor allele frequencies of rs1107946 and rs1800012 were 0.15 and 0.20 in osteoporotic women, 0.18 and 0.18 in osteopenic and 0.20 and 0.17 in women having normal bone mass. An allele dose effect with BMD of lumbar spine has been exhibited by major allele G of rs1107946 (GG: 0.86 g/cm(2), GT: 0.91 g/cm(2) and TT: 0.93 g/cm(2)) and minor allele T of rs1800012 (GG: 0.91 g/cm(2), GT: 0.87 g/cm(2) and TT: 0.81 g/cm(2)). Disease association analysis revealed a haplotype GT that confers approximately threefold higher risk of osteoporosis in the carriers (OR 3.12, 95% CI 1.24-8.88, P = 0.008) after adjusting the confounding effect of age, BMI and years since menopause. These results suggest that GT haplotype of COL1A1 gene is associated with a higher risk of postmenopausal osteoporosis in Northwest Indian women. PMID- 22057140 TI - Sequelae of osteomyelitis variolosa: a case report. AB - Osteomyelitis variolosa is an osteoarticular complication of small pox infection. We are presenting a case of osteomyelitis variolosa, who presented to us with fracture of ankle on the involved side with other orthopedic sequelae of small pox infection, which he contracted during his childhood period. We have discussed the distinguishing clinical and radiological features of osteomyilitis variolosa. PMID- 22057141 TI - Prevalence of chronic widespread pain and fibromyalgia syndrome: a Korean hospital-based study. AB - This study was conducted to estimate the point prevalence of chronic widespread pain (CWP) and fibromyalgia syndrome (FMS) in a primary care center of a hospital in Korea. CWP was defined as pain lasting more than 3 months involving all the classified pain sites (axial, left and right, above and below waist). FMS was diagnosed by the American College of Rheumatology (ACR) criteria and also by clinical judgment of a physician. All 1,077 subjects were classified into three groups as no chronic pain (NCP), chronic regional pain (CRP), and CWP. CRP was defined as chronic pain with the exception of CWP. The point prevalence of CWP was 6.5% (95% confidence interval (CI) 0.2-12.8) and the point prevalence of FMS was 1.7% (95% CI 0.0-4.9) by ACR criteria and 2.3% (95% CI 0.0-6.1) by clinical judgment, respectively. We also analyzed the differential demographic characteristics among patients with NCP, CRP, and CWP. When compared to NCP, CWP was significantly associated with the female gender after adjusting for other variables (odds ratio 4.2; 95% CI 1.4-12.4, P = 0.009). Compared to NCP, CWP patients had lower levels of education (P = 0.018), a lower likelihood of a professional occupation (P = 0.014), infrequent alcohol intake (P = 0.014) and a lower proportion of current smokers (P = 0.003) based on a univariable analysis. In this Korean hospital-based study, CWP patients were common and had different demographic characteristics and life habits from NCP. PMID- 22057142 TI - Serum melatonin level in ankylosing spondylitis: is it increased in active disease? AB - In the recent years, the role of melatonin (MLT) in the pathogenesis of inflammatory arthritis has been investigated, and the serum levels of MLT have been evaluated, but clinical study concerning MLT and ankylosing spondylitis (AS) is little reported in literature. We aimed to investigate the serum levels of MLT and their relation with the disease activity parameters of patients with AS. Forty AS patients and 40 healthy controls (matched for age and sex with the patients) participated in this study. Demographic and clinical data were collected and assessed. Disease activity of AS patients was assessed clinically according to the Bath AS Disease Activity Index (BASDAI), while AS functional impairment was assessed using the Bath AS Functional Index (BASFI). Serum samples were collected from all subjects to evaluate serum MLT, ESR, and CRP. Serum MLT levels were significantly increased in AS patients as compared to healthy controls (95% CI: 4.63, 8.77, P < 0.001). ESR and CRP are significantly higher in the AS patients compared with the controls (P < 0.001). AS patients with active disease had significantly higher ESR (P = 0.0151), CRP (P = 0.0124), and BASFI (P = 0.0016). Also, the MLT serum level in AS patients with BASDAI >=40 was 39.7 +/- 6.2 pg/ml compared with 35.2 +/- 3.5 pg/ml in AS patients with BASDAI <40 (95% CI: 1.22, 7.78, P = 0.0106). Also, serum MLT level was significantly higher in the AS patients with enthesopathy than those without enthesopathy. Serum MLT levels were correlated with the duration of morning stiffness, BASDAI, BASFI, and CRP but not with ESR or duration of the disease. Serum levels of MLT were significantly increased in AS patients as compared to healthy controls. MLT levels correlated positively with BASDAI, BASFI, duration of morning stiffness, and CRP levels. Thus, it seems that MLT levels reflect the disease activity in AS patients. PMID- 22057143 TI - The major determinants of arterial stiffness in Korean patients with rheumatoid arthritis are age and systolic blood pressure, not disease-related factors. AB - Patients with rheumatoid arthritis are at increased risk of cardiovascular morbidity and mortality. This study was undertaken to investigate the prevalence of peripheral arterial disease, and to identify factors, especially those related to rheumatoid arthritis, influencing arterial stiffness in Korean patients with rheumatoid arthritis. A total of 262 patients with rheumatoid arthritis managed in a tertiary clinic were included. Ankle-brachial index and brachial-ankle pulse wave velocity were measured. Rheumatoid arthritis-related factors were determined, as well as the traditional cardiovascular risk factors. The prevalence of peripheral arterial disease was only 1.5%. Mean pulse wave velocity was 1,559 +/- 354 cm/s. Age, body mass index, blood pressure, lipid profile, and glucose, not rheumatoid arthritis-related factors such as disease duration, seropositivity and disease activity, were significantly correlated with pulse wave velocity. Moreover, stepwise multiple regression analysis revealed that only age over 65 (OR = 9.1, 95% CI 4.3-19.1, P < 0.001), systolic blood pressure over 140 mmHg (OR = 15.7, 95% CI 7.4-33.1, P < 0.001), and corticosteroid use (OR = 2.1, 95% CI 1.03-4.3, P = 0.04) were independent risk factors for high pulse wave velocity. The prevalence of peripheral arterial disease in Korean patients with rheumatoid arthritis is very low. Among the many factors related to arterial stiffness, only old age, high systolic blood pressure, and, to a certain extent, corticosteroid use appear to be major determinants, especially in clinical setting with relatively well controlled patients with rheumatoid arthritis. PMID- 22057144 TI - Assessment of hand functions in rheumatoid arthritis using SF-SACRAH (short form score for the assessment and quantification of chronic rheumatoid affections of the hands) and its correlation to disease activity. AB - Rheumatoid arthritis activity is generally evaluated by using DAS-28 score. But this does not reflect the extent of functional hand impairment, a decisive parameter for patient wellbeing as well as for work disability. Several questionnaires to quantify the hand involvement in RA have been elaborated, amongst which SACRAH has been popular since 2003. But this requires evaluating 23 questions on a visual analogue scale. The questions were reduced to 12 in modified-SACRAH (M-SACRAH) and to only five questions in short form SACRAH (SF SACRAH) so as to make it easily applicable in daily clinical practice. A study was planned to compare M-SACRAH (already validated) to SF-SACRAH in Indian population as no Indian data are available on the same. A total of 100 patients of RA were evaluated for disease activity using DAS-28 score and hand functions using M-SACRAH and SF-SACRAH. The M-SACRAH and SF-SACRAH were then compared based on DAS-28 scores; also M-SACRAH was compared to SF-SACRAH using Spearman's correlation coefficient. The mean value of DAS-28 score was 3.15 +/- 0.86. The mean value of SF-SACRAH was 8.065 +/- 7.44, and mean value of M-SACRAH was 201.7 +/- 201.1008. The correlation of DAS-28 score to SF-SACRAH and M-SACRAH was significant in moderate and high disease activity but insignificant in remission and low disease activity state. The correlation between M-SACRAH and SF-SACRAH showed a spearman's coefficient of 0.998 with a P value of <0.001 (significant correlation). Correlation was significant for all disease activity states and for remission. The study suggests that the disease activity of rheumatoid arthritis (as assessed by DAS-28 score) has a poor correlation with hand functions (as assessed by M-SACRAH and SF-SACRAH) especially in low disease activity and remission states. Further, M-SACRAH and SF-SACRAH are significantly correlated. Therefore, it is suggested that RA patients should be assessed by SF-SACRAH (which includes five questions only) in addition to DAS-28 scoring for better evaluation of hand functions, a detrimental factor in day to day performance of RA patients. PMID- 22057145 TI - The value of procalcitonin measurements in children with familial Mediterranean fever. AB - It is well known that the serum procalcitonin (PCT) levels increase in severe bacterial infections. However, there is little information about the levels of PCT in diverse diseases except mainly the infectious diseases. The aim of this study was to investigate the progress of serum levels of PCT together with traditional acute phase reactants in children with familial Mediterranean fever (FMF) during the attack and attack-free periods and to test whether PCT could help to diagnose the attack in FMF patients. The study group comprised 21 FMF patients (mean age 10 +/- 4.6 years) and 19 healthy controls (mean age 10.6 +/- 4.2 years). Serum levels of PCT and traditional acute phase reactants were measured during the attack and attack-free periods. Blood samples were obtained within the first 6-24 h of the attack period, 7 days later, and at least 2 months after the attack. Traditional acute phase reactants (hs-CRP, ESR, and fibrinogen) during the attack period were significantly higher than the attack-free levels and controls. PCT levels of the FMF patients during the attack period were also significantly higher than the attack-free and control group levels (median values, 0.044 ng/ml vs. 0.028 ng/ml and 0.031 ng/ml, P = 0.04, respectively). Although this difference was statistically significant (P = 0.04), median PCT values of the attack, attack-free period, and healthy subjects were lower than 0.05 ng/ml. As a result, these findings suggested that PCT levels were not conspicuously affected from inflammation and could not be used as a descriptive marker for attack in FMF patients. PMID- 22057146 TI - Clinical findings of vertebral osteomyelitis: Brucella spp. versus other etiologic agents. AB - We aimed to evaluate patients with vertebral osteomyelitis (VO) in our region and to compare the clinical and laboratory parameters of brucellar and non-brucellar VO patients (NBVO). This retrospective study included 80 patients with VO followed in our hospital between August 2004 and September 2010. The distribution of gender was 43 females (53.8%) and 37 males (46.2%) with average age of 52.5. Patients with brucellar vertebral VO (BVO; n = 30) accounted for 37.5% of all patients, and the rest (n = 50) were with NBVO. Co-morbidities existed in 32.5% of patients. In statistical comparison of VO patients who had the Brucella spp. as the infectious agent with patients of VO by non-brucellar pathogens, the following factors were found out to be significantly associated with BVO; low Charlson score (P = 0.0001), lower co-incidence with chronic renal failure (P = 0.001), high frequency of constitutional symptoms (P = 0.006), fever (P = 0.005), low-level inflammatory markers (WBC; Neutrophil; ESR; CRP, P values 0.006; 0.001; 0.022; 0.002, respectively), low-rate surgical treatment (P = 0.02) and culture positivity (P = 0.0001) and higher hemoglobin, total protein, albumin values (P = 0.002; 0.032; 0.016, respectively). VO may be strongly associated with brucellosis in patients presenting with fever and symptoms, low Charlson score and indistinct inflammatory markers. PMID- 22057147 TI - Unusual bridge ossification of pubic symphysis in diffuse idiopathic skeletal hyperostosis. PMID- 22057148 TI - Left or right hand of Cosimo I de' Medici? PMID- 22057149 TI - Lack of association between flow-mediated endothelium-dependent vasodilatation and biomarkers of endothelial dysfunction in patients with severe rheumatoid arthritis. PMID- 22057150 TI - [Does FVIII-activity increase with age in patients with haemophilia A and carriers of haemophilia A?]. AB - The retrospective cohort study surveys the influence of age, co-morbidity and laboratory values on FVIII-activity (FVIII:C) in patients with haemophilia A with (mild n = 48, moderate n = 10, severe n = 7 and carriers n = 23). Median observation was 19 years for patients with haemophilia A and 9,5 years for carriers. RESULTS: FVIII:C levels collected from patients with mild haemophilia A displayed a significant median increase of 6.5% with proceeding age (p = 0.0013). Patients with moderate haemophilia A (and carriers of haemophilia A) showed a non significant median increase of 1.05% (carriers 8%). Eight patients showed FVIII:C levels at last blood withdrawal that indicated a change of severity from moderate to mild haemophilia A. A significant correlation was found between FVIII:C and VWF:RCo (p = 0.0203) and AFP (p < 0.0005). The correlation between FVIII:C and triglycerides and LDH was significant negative (p < 0.0005). No significant correlation could be found for FVIII:C and co-morbidity, fibrinogen, cholesterol and VWF:Ag. PMID- 22057151 TI - Quality improvement guidelines for recording patient radiation dose in the medical record for fluoroscopically guided procedures. PMID- 22057152 TI - Psychophysiological and electrophysiological testing of olfactory and gustatory function in patients with multiple sclerosis. AB - The olfactory (OF) and gustatory function in multiple sclerosis (MS) patients and possible influencing variables of the disease, such as depression or fatigue, were determined. In an open prospective controlled clinical study 30 patients with MS and 30 healthy controls matched for age, sex and smoking-habits were investigated. With Mini Mental State Examination cognitive dysfunction was excluded, with Expanded Disability Status Scale the patient's ability to accomplish the tests was ensured. The severity of depression was measured with the self-reported Beck Depression Inventory. The orthonasal olfactory function was derived with olfactory event related potentials (OERP) and TDI-score (Threshold, Discrimination and Identification, Sniffin' Sticks). Retronasal olfactory function was tested with Taste-Powder-score, gustatory function with Taste-strip-score. There was a significant loss of olfactory function measured with TDI-score [12/30 (40%), p = 0.002] and gustatory function [5/23 (21.7%), p < 0.001] in MS-patients, 23.8% (5/21) of MS-patients showed hyposmia with OERPs, significantly correlating with the TDI-score (p = 0.03). The Expanded Disability Status scale score inversely correlated with the TDI-score (p = 0.002). This study confirms the incidence of olfactory disorder in MS-patients and reveals a frequent gustatory deficit. The Identification subtest can be proposed as a marker of the OF in MS-patients: it includes complex cognitive tasks and may be influenced by depression and fatigue, which are common symptoms of MS. It inversely correlates with the disability status. PMID- 22057153 TI - Reliability and efficacy of a new CO2 laser hollow fiber: a prospective study of 39 patients. AB - We present the first series of patients treated by transoral laser surgery (TLS) using the new AcuPulse 40WG CO(2) laser with the FiberLase flexible waveguide (CO(2) LWG) (Lumenis, Santa Clara, CA) with the objective to test its reliability and efficacy. Patients older than 18 years, with oral, pharyngo-laryngeal or tracheal benign or premalignant lesions were enrolled after signing an informed consent. This prospective study was conducted between October 2010 and May 2011 in two tertiary care university hospitals. Thirty-nine patients were enrolled in the study. The mean age was 47.9 years (range 18-86 years). There were 21 women and 18 men. Thirteen patients had hypertrophy of lymphoid tissue (palatine and or lingual), nine patients had granulomas, four patients had an exudative glottic lesion, three patients had severe dysplasia (glottic and supraglottic), three patients had leukoplakia, two patients had glottal cysts, two patients had laryngeal papilloma, two patients had bilateral paralysis of the vocal folds and one patient suffered from spasmodic dysphonia. Eighty-two percent of the procedures were performed under general anesthesia with laryngo-tracheal intubation. The CO(2) fiber passed through a handpiece was used with a microscope in the majority of the procedures. The laser delivery mode parameter used was: SuperPulse or Continuous Wave. Power levels were 3-15 Watts (W), continuous delivery. Each procedure utilized one CO(2) fiber which performed adequately throughout the procedure. No complications were noted with the use of this technology. A bipolar cautery was needed to control bleeding in eight procedures; all these procedures were tonsillectomies. The CO(2) LWG is a safe and reliable tool for TLS. It is durable enough to last through the entire surgical procedure without the need for replacement. Its use must be tailored depending on the type and location of the lesion, the CO(2) lasers tissue effects as well as the surgeon's experience. PMID- 22057154 TI - Suppression of spontaneous nystagmus during different visual fixation conditions. AB - Analysis of spontaneous nystagmus is important in the evaluation of dizzy patients. The aim was to measure how different visual conditions affect the properties of nystagmus using three-dimensional video-oculography (VOG). We compared prevalence, frequency and slow phase velocity (SPV) of the spontaneous nystagmus with gaze fixation allowed, with Frenzel's glasses, and in total darkness. Twenty-five patients (35 measurements) with the peripheral vestibular pathologies were included. The prevalence of nystagmus with the gaze fixation was 40%, and it increased significantly to 66% with Frenzel's glasses and regular room lights on (p < 0.01). The prevalence increased significantly to 83% when the regular room lights were switched off (p = 0.014), and further to 100% in total darkness (p = 0.025). The mean SPV of nystagmus with visual fixation allowed was 1.0 degrees /s. It increased to 2.4 degrees /s with Frenzel's glasses and room lights on, and additionally to 3.1 degrees /s, when the regular room lights were switched off. The mean SPV in total darkness was 6.9 degrees /s. The difference was highly significant between all test conditions (p < 0.01). The frequency of nystagmus was 0.7 beats/s with gaze fixation, 0.8 beats/s in both the test conditions with Frenzel's glasses on, and 1.2 beats/s in total darkness. The frequency in total darkness was significantly higher (p < 0.05) than with Frenzel's glasses, and more so than with visual fixation (p = 0.003). The VOG in total darkness is superior in detecting nystagmus, since Frenzel's glasses allow visual suppression to happen, and this effect is reinforced with gaze fixation allowed. Strict control of visual surroundings is essential in interpreting peripheral nystagmus. PMID- 22057155 TI - Effect of bariatric surgery on obesity-related infertility. AB - BACKGROUND: There is a strong association between obesity and infertility, and weight loss can increase fecundity in obese women. In an attempt to determine the effect of bariatric surgery on obesity-related infertility, we reviewed the fertility outcomes after intragastric balloon placement, adjustable gastric banding, sleeve gastrectomy, and gastric bypass in childbearing women with a diagnosis of infertility at a university hospital in Italy. METHODS: This was a retrospective study of 110 obese infertile women. We evaluated the effectiveness of bariatric surgery in improving fertility, assessing the influence of age, surgical technique, co-morbidities (hypertension and diabetes), weight loss, and body mass index before and after surgery. RESULTS: Of these 110 women who had tried unsuccessfully to become pregnant before weight loss, 69 became pregnant afterward. The pregnancies proceeded without complications and ended with a live birth. Only the weight loss (odds ratio 20.2, P = .001) and the achieved body mass index (P = .001) after surgery were the predictors of pregnancy. CONCLUSION: Bariatric surgery might be effective in young infertile obese women who wish to become pregnant. Weight loss appears to be independent from the surgical technique in determining the increase in the pregnancy rate as well as the body mass index achieved at pregnancy. PMID- 22057156 TI - Particulate matter neurotoxicity in culture is size-dependent. AB - Exposure to particulate matter (PM) air pollution produces inflammatory damage to the cardiopulmonary system. This toxicity appears to be inversely related to the size of the PM particles, with the ultrafine particle being more inflammatory than larger sizes. Exposure to PM has more recently been associated with neurotoxicity. This study examines if the size-dependent toxicity reported in cardiopulmonary systems also occurs in neural targets. For this study, PM ambient air was collected over a 2 week period from Sterling Forest State Park (Tuxedo, New York) and its particulates sized as Accumulation Mode, Fine (AMF) (>0.18 1MUm) or Ultrafine (UF) (<0.18MUm) samples. Rat dopaminergic neurons (N27) were exposed to suspensions of each PM fraction (0, 12.5, 25, 50MUm/ml) and cell loss (as measured by Hoechst nuclear stain) measured after 24h exposure. Neuronal loss occurred in response to all tested concentrations of UF (>12.5MUg/ml) but was only significant at the highest concentration of AMF (50MUg/ml). To examine if PM size-dependent neurotoxicity was retained in the presence of other cell types, dissociated brain cultures of embryonic rat striatum were exposed to AMF (80MUg/ml) or UF (8.0MUg/ml). After 24h exposure, a significant increase of reactive nitrogen species (nitrite) and morphology suggestive of apoptosis occurred in both treatment groups. However, morphometric analysis of neuron specific enolase staining indicated that only the UF exposure produced significant neuronal loss, relative to controls. Together, these data suggest that the inverse relationship between size and toxicity reported in cardiopulmonary systems occurs in cultures of isolated dopaminergic neurons and in primary cultures of the rat striatum. PMID- 22057157 TI - Incidence of Abcd1 level on the induction of cell death and organelle dysfunctions triggered by very long chain fatty acids and TNF-alpha on oligodendrocytes and astrocytes. AB - X-linked adrenoleukodystrophy (X-ALD) is characterized by ABCD1 deficiency. This disease is associated with elevated concentrations of very long chain fatty acids (C24:0 and C26:0) in the plasma and tissues of patients. Under its severe form, brain demyelination and inflammation are observed. Therefore, we determined the effects of C24:0 and C26:0 on glial cells:oligodendrocytes, which synthesize myelin, and astrocytes, which participate in immune response. So, 158N murine oligodendrocytes, rat C6 glioma cells, rat primary cultures of neuronal-glial cells, and of oligodendrocytes were treated for various periods of time in the absence or presence of C24:0 and C26:0 used at plasmatic concentrations found in X-ALD patients (1-5 MUM) and higher (10, 20, 40 MUM). To evaluate the importance of extrinsic and intrinsic factors, the part taken by TNF-alpha and reduced Abcd1 level was studied. Whatever the cells considered, no effects on cell growth and/or viability were detected at 1-5 MUM, more or less pronounced effects were identified at 10 MUM, and an induction of cell death with increased permeability to propidium iodide and loss of transmembrane mitochondrial potential was observed at 20-40 MUM. On 158N, cell death was characterized by (i) an increased superoxide anion production at the mitochondrial level; (ii) the presence of vacuoles of different sizes and shapes; a destabilization of lysosomal membrane and a cytoplasmic redistribution of lysosomes; (iii) a modulation of Abcd3/PMP70 and Acox-1 protein expression, and a decrease in catalase activity at the peroxisomal level. When TNF-alpha was combined with C24:0 or C26:0 and used on 158N cells, C6 cells, and on 158N cells after siRNA mediated knockdown of Abcd1, no or slight potentiation was revealed. Thus, on the different cell models used, an induction of cell death with marked cellular dysfunctions at the mitochondrial, lysosomal, and peroxisomal levels were found with C24:0 and C26:0 at 20 MUM and higher. However, in our experimental conditions, plasmatic concentrations of these fatty acids were unable to induce cell death, and organelle dysfunctions on oligodendrocytes and astrocytes, and additional intrinsic and environmental factors, such as reduced Abcd1 level and/or TNF alpha, were ineffective to potentiate their side effects. PMID- 22057158 TI - AURA: Atlas of UTR Regulatory Activity. AB - SUMMARY: The Atlas of UTR Regulatory Activity (AURA) is a manually curated and comprehensive catalog of human mRNA untranslated regions (UTRs) and UTR regulatory annotations. Through its intuitive web interface, it provides full access to a wealth of information on UTRs that integrates phylogenetic conservation, RNA sequence and structure data, single nucleotide variation, gene expression and gene functional descriptions from literature and specialized databases. AVAILABILITY: http://aura.science.unitn.it CONTACT: aura@science.unitn.it; dassi@science.unitn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22057159 TI - Gene Ontology-driven inference of protein-protein interactions using inducers. AB - MOTIVATION: Protein-protein interactions (PPIs) are pivotal for many biological processes and similarity in Gene Ontology (GO) annotation has been found to be one of the strongest indicators for PPI. Most GO-driven algorithms for PPI inference combine machine learning and semantic similarity techniques. We introduce the concept of inducers as a method to integrate both approaches more effectively, leading to superior prediction accuracies. RESULTS: An inducer (ULCA) in combination with a Random Forest classifier compares favorably to several sequence-based methods, semantic similarity measures and multi-kernel approaches. On a newly created set of high-quality interaction data, the proposed method achieves high cross-species prediction accuracies (Area under the ROC curve <= 0.88), rendering it a valuable companion to sequence-based methods. AVAILABILITY: Software and datasets are available at http://bioinformatics.org.au/go2ppi/ CONTACT: m.ragan@uq.edu.au. PMID- 22057160 TI - Large-scale motif discovery using DNA Gray code and equiprobable oligomers. AB - MOTIVATION: How to find motifs from genome-scale functional sequences, such as all the promoters in a genome, is a challenging problem. Word-based methods count the occurrences of oligomers to detect excessively represented ones. This approach is known to be fast and accurate compared with other methods. However, two problems have hampered the application of such methods to large-scale data. One is the computational cost necessary for clustering similar oligomers, and the other is the bias in the frequency of fixed-length oligomers, which complicates the detection of significant words. RESULTS: We introduce a method that uses a DNA Gray code and equiprobable oligomers, which solve the clustering problem and the oligomer bias, respectively. Our method can analyze 18 000 sequences of ~1 kbp long in 30 s. We also show that the accuracy of our method is superior to that of a leading method, especially for large-scale data and small fractions of motif-containing sequences. AVAILABILITY: The online and stand-alone versions of the application, named Hegma, are available at our website: http://www.genome.ist.i.kyoto-u.ac.jp/~ichinose/hegma/ CONTACT: ichinose@i.kyoto u.ac.jp; o.gotoh@i.kyoto-u.ac.jp PMID- 22057161 TI - Detecting differential binding of transcription factors with ChIP-seq. AB - SUMMARY: Increasing number of ChIP-seq experiments are investigating transcription factor binding under multiple experimental conditions, for example, various treatment conditions, several distinct time points and different treatment dosage levels. Hence, identifying differential binding sites across multiple conditions is of practical importance in biological and medical research. To this end, we have developed a powerful and flexible program, called DBChIP, to detect differentially bound sharp binding sites across multiple conditions, with or without matching control samples. By assigning uncertainty measure to the putative differential binding sites, DBChIP facilitates downstream analysis. DBChIP is implemented in R programming language and can work with a wide range of sequencing file formats. AVAILABILITY: R package DBChIP is available at http://pages.cs.wisc.edu/~kliang/DBChIP/ CONTACT: kliang@stat.wisc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22057162 TI - A robust clustering algorithm for identifying problematic samples in genome-wide association studies. AB - SUMMARY: High-throughput genotyping arrays provide an efficient way to survey single nucleotide polymorphisms (SNPs) across the genome in large numbers of individuals. Downstream analysis of the data, for example in genome-wide association studies (GWAS), often involves statistical models of genotype frequencies across individuals. The complexities of the sample collection process and the potential for errors in the experimental assay can lead to biases and artefacts in an individual's inferred genotypes. Rather than attempting to model these complications, it has become a standard practice to remove individuals whose genome-wide data differ from the sample at large. Here we describe a simple, but robust, statistical algorithm to identify samples with atypical summaries of genome-wide variation. Its use as a semi-automated quality control tool is demonstrated using several summary statistics, selected to identify different potential problems, and it is applied to two different genotyping platforms and sample collections. AVAILABILITY: The algorithm is written in R and is freely available at www.well.ox.ac.uk/chris-spencer CONTACT: chris.spencer@well.ox.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 22057163 TI - Synthesis and anticonvulsant evaluation of dimethylethanolamine analogues of valproic acid and its tetramethylcyclopropyl analogue. AB - BACKGROUND: Valproic acid (VPA) is a major antiepileptic drug (AED) that is less potent than other AEDs. 2,2,3,3-Tetramethylcyclopropanecarboxylic acid (TMCA) is an inactive cyclopropyl analogue of VPA that serves as a starting material for the synthesis of CNS-active compounds. METHODS: New conjugation products between N,N'-dimethylethanolamine to VPA and TMCA to form N,N-dimethylethanolamine valproate (DEVA) and N,N-dimethylethanolamine 2,2,3,3-tetramethylcyclopropionate were synthesized and their anticonvulsant activity was assessed in the maximal electroshock seizure (MES) and subcutaneous metrazol (scMet) seizure tests and the hippocampal kindling model in mice and/or rats. An amide analogue of DEVA (DEVAMIDE) was also synthesized and evaluated. The pharmacokinetics of DEVA and DEVAMIDE was comparatively evaluated in rats. RESULTS: In rats DEVA acted as a prodrug of VPA and had ED(50) values of 73 mg/kg and 158 mg/kg in the MES and the hippocampal kindling models, respectively. At these two anticonvulsant models DEVA was seven-times more potent than VPA. DEVAMIDE was active in the MES test at doses of 100 mg/kg (mice) and its rat-MES-ED(50)=38.6 mg/kg however, its protective index (PI=TD(50)/ED(50)) was twice lower than DEVA's PI. The TMCA analogues were inactive at the mice MES and scMet models. DEVA underwent rapid metabolic hydrolysis to VPA and consequently, in its pharmacokinetic analysis only VPA plasma levels were monitored. In contrast, DEVAMIDE was stable in whole blood. CONCLUSION: DEVA acts in rats as a prodrug of VPA yet shows a more potent anticonvulsant activity than VPA. DEVAMIDE acted as the drug on its own and was more potent than DEVA at the rat-MES test. PMID- 22057164 TI - Generation and biological properties of a recombinant dodecahedron containing the short fiber protein of the human adenovirus 41. AB - OBJECTIVE: In order to gain further insight into the function of the enteric adenovirus short fiber (SF), we have constructed a recombinant dodecahedron containing the SF protein of HAdV-41 and the HAdV-3 penton base. METHODS: Recombinant baculoviruses expressing the HAdV-41 SF protein and HAdV-3 penton base were cloned and amplified in Sf9 insect cells. Recombinant dodecahedra were expressed by coinfection of High FiveTM cells with both baculoviruses, 72 h post infection. Cell lysate was centrifuged on sucrose density gradient and the purified recombinant dodecahedra were recovered. RESULTS: Analysis by negative staining electron microscopy demonstrated that chimeric dodecahedra made of the HAdV-3 penton base and decorated with the HAdV-41 SF were successfully generated. Next, recombinant dodecahedra were digested with pepsin and analyzed by Western blot. A 'site-specific' proteolysis of the HAdV-41 SF was observed, while the HAdV-3 penton base core was completely digested. CONCLUSION: These results show that, in vitro, the HAdV-41 SF likely undergoes proteolysis in the gastrointestinal tract, its natural environment, which may facilitate the recognition of receptors in intestinal cells. The results obtained in the present study may be the basis for the development of gene therapy vectors towards the intestinal epithelium, as well as orally administered vaccine vectors, but also for the HAdV-41 SF partner identification. PMID- 22057165 TI - [Role of the kallikrein kinin system and its interrelationship with vasoactive systems in pregnancy]. AB - Glomerular hyperfiltration and increased sodium reabsorption are key factors for the development of the fetus and placenta in pregnancy. These adjustments result from hemodynamic and renal factors involving vasoactive systems. It was demonstrated in rats that activation of KKS precedes the installation of glomerular hyperfiltration as aprotinin prevents the increase in glomerular filtration. In addition, individual or associated inhibition of specific kallikrein kinin system effectors, prostaglandins (PGs) and nitric oxide (NO), confirm the glomerular filtration rate dependence of KKS during pregnancy. It was also found that the renin-angiotensin system (RAS) contributes to glomerular hyperfiltration as this is affected by the administration of RAS blockers. The peak of hyperfiltration maximum inhibition was obtained by the blockade of both systems (KKS and RAS). In addition, strategies used to alter the glomerular hyperfiltration and increased sodium reabsorption during pregnancy, showed abnormalities in the development of the fetus and placenta, fewer offspring, more fetus resorptions and intrauterine growth retardation. KKS inhibitors associated with RAS or nitric oxide blockers showed the greatest impact. As a consequence, it was demonstrated that KKS plays a central role in the adaptation phenomenom that accompanies normal pregnancy. The interplay of KKS with several vasoactive systems, seem to arrange a network involved in the hemodynamic adaptations to allow the proper development of pregnancy and the fetus and placenta. PMID- 22057166 TI - [Role of three ELISA tests using promastigote homogenates of Leishmania braziliensis, L. amazonensis and L. guyanensis in the diagnosis of tegumentary leishmaniasis]. AB - It is important to know whether the variability of species of Leishmania parasites circulating in a region affects the performance of the ELISA test for the diagnosis of leishmaniasis. Therefore, the aim of this study was to analyze the reactivity of the ELISA using homogenates of promastigotes of Leishmania (V.) braziliensis (ELISAb), Leishmania (L) amazonensis (ELISAa) and Leishmania (V.) guyanensis (ELISAg) against different sera groups. Samples from individuals with cutaneous leishmaniasis (n = 37), mucocutaneous leishmaniasis (n = 8), healthy controls (n = 52), persons infected with Trypanosoma cruzi (n = 11) and mixed infections (n = 14) were included in the study. We calculated sensitivities, specificities, cut offs, and predictive values for the three tests and compared them using ANOVA, kappa index, ROC curves comparison, and confidence intervals calculated by the bootstrap method. Significant differences were found when comparing the OD levels of sera from patients with cutaneous leishmaniasis against healthy controls, but there were no differences when comparing the different ELISAs. The sensitivities calculated for ELISAb and ELISAa were 84.6 and of 88.5% for ELISAg, while the value of specificity for the three tests was 96.2. The kappa index (0.87) and comparison of ROC curves showed similar performance for the three ELISAs (p = 0.225). The high reactivity obtained for these ELISAs in sera of patients with mucocutaneous leishmaniasis indicates this test as an important complement in the diagnosis of the disease. PMID- 22057167 TI - [Trichomonas vaginalis prevalence in sex workers]. AB - Trichomoniasis is a sexually transmitted infection (STI) usually associated to vaginitis, urethritis, cervicitis and pelvic inflammatory disease, which can cause infertility. The aim of this retrospective longitudinal study was to determine Trichomonas vaginalis prevalence in a population of male and female sex workers in Mendoza, Argentina. A cohort of 720 people who attended the STI Program in this province was retrospectively analyzed. From February 2007 up to June 2009, 1692 samples were processed using a reposition sampling method. The age and sex distribution of the population was: 687 women/33 men, from 15 to 65 years old. Trichomoniasis prevalence determined for this population at risk was 7.6% in women only, men did not present infection. The high prevalence shown for this risk group suggests a great vulnerability of this population to contract other more serious STIs. In another sense, it also shows a remarkable lack in the use of mechanical barriers to prevent sexually transmitted diseases (STDs). The present research justifies the elaboration of standardized procedures guide to diagnose T. vaginalis within the framework of the Reproductive Health Program (PROSAR). PMID- 22057168 TI - HIV and pregnancy: maternal and neonatal evolution. AB - Data regarding epidemiological aspects, antiretroviral drug safety, and outcomes of HIV-infected pregnant women and their newborns are limited in Argentina. We underwent a retrospective analysis of registries of HIV-infected pregnant women assisted at Helios Salud, Buenos Aires, Argentina (1997-2006). Variables associated with preterm delivery and neonatal complications were analyzed by univariate and logistic regression analyses. A total of 204 mother-child binomium were included. Maternal age (median): 29 years; 32.5% without prior diagnosis of HIV-infection. Baseline median CD4 T-cell count: 417 cell/ul; 98% received antiretroviral drugs during pregnancy [2 nucleoside analogs plus either nevirapine (55%) or a protease inhibitor (32%)]. Overall incidence of toxicity was 12.5%: rash (8%), anemia (3.5%) and hepatotoxicity (1%). Rash was associated with exposure to nevirapine. Eighty one percent and 50% reached HIV-viral loads <1000 and <50 copies/ml at the end of pregnancy, respectively. Twenty six percent had obstetric complications and 16% had preterm delivery. Of the newborns, 1.6% had congenital defects and 9% had neonatal complications. Overall neonatal mortality was 1% and perinatal transmission was 0.7%. Protease inhibitor use and obstetric complications were associated to preterm delivery while obstetric complications were associated with neonatal complications. In our population, hepatotoxicity was low despite frequent use of nevirapine. Protease inhibitor use was associated to preterm delivery. A favorable virological response and a low rate of perinatal transmission was observed, what supports the consensus that antiretroviral therapy benefits during pregnancy outweigh risks of maternal and neonatal adverse events. PMID- 22057169 TI - [Treatment of compression of the left main coronary artery in patients with pulmonary hypertension]. AB - Chest pain is a frequent symptom in patients with pulmonary hypertension of any etiology. Its pathophysiology has not been clearly established, the proposed causes are ischemia due to increased right ventricle wall stress, transient increased pulmonary hypertension resulting in acute pulmonary artery dilatation and external compression of the left main coronary artery (LMCA) by a dilated pulmonary artery. We report and discuss here three cases where the association between chest pain and compression of the LMCA by a dilated pulmonary artery could be shown, and they were treated with coronary stenting. PMID- 22057170 TI - [Contrast induced nephropathy in acute coronary syndrome]. AB - Contrast induced nephropathy (CIN) is one of the most frequent causes of acute renal failure in hospitalized patients. It is associated with an increase in morbidity and mortality in patients hospitalized for acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Risk factors and prevention strategies are not well defined. The aim of this study was to assess the incidence and clinical risk factors associated to the development of contrast induced nephropathy in patients hospitalized for ACS. In a retrospective cohort we analyzed consecutive patients hospitalized for ACS undergoing urgent PCI within 72 hours from the admission. CIN was defined as a 25% increase of creatinine levels from baseline at 48 hours from the PCI. The inclusion period was from January 1, 2004 to June 30, 2010. A total of 125 patients were analyzed, and CIN occurred in 13 (10.4%) patients. An independent association was found between age (OR 1.05; 95% CI 1.004 to 1.11; p = 0.034), multiple vessel angioplasty (OR 2.2; 95% IC 1.07 to 4.8; p = 0.03) and the volume of contrast infused (OR 1.007; 95% CI 1.001 to 1.01; p = 0.014) with the development of CIN. PMID- 22057171 TI - [Morbidity and mortality of carotid endarterectomy]. AB - Clinical trials in academic centers with high selected surgeons have demonstrated the effectiveness of carotid endarterectomy (CE) in addition to best medical treatment in symptomatic and asymptomatic patients with moderate to severe stenosis. International guidelines recommend that the procedure should be done in centers with morbidity and mortality rates of less than 6% for symptomatic and 3% for asymptomatic patients. We evaluated the morbidity and mortality of CE in our institution. This was defined by the presence of stroke, myocardial infarction and/or death within 30 days of surgery. Surgery was indicated in symptomatic patients with stenosis greater than 50%. For asymptomatic or symptomatic patients with stenosis = 50% treatment was decided on a case-by-case basis. All patients were examined by a neurologist with and a cardiologist before and after the procedure. Intraoperative monitoring with transcranial Doppler was routinely used in patients with adequate ultrasonic window. We evaluated 306 procedures. No deaths occurred. Perioperative morbidity was 2.6% for both, symptomatic and asymptomatic subjects. These numbers compared favorably with those reported by other centers in Latin America and Europe. In conclusion, CE can be performed in routine clinical practice with morbidity and mortality results within those recommended by international guidelines. PMID- 22057172 TI - [Fibrillary glomerulo-nephritis: a rare form of glomerular disease with organized deposits]. AB - We describe the case of a 67 year-old female who presented weakness and fatigue. Laboratory data showed nephrotic level of proteinuria and dyslipidemia. A renal biopsy was performed, and studied by light microscopy, immuno-fluorescence and electron microscopy. Ultra-structural analysis revealed the existence of organized fibrillary deposits, straight and without ramifications, the thickness of which ranged from 15 to 20 nm. These fibres were identified, by light microscopy, as slightly nodular mesangial expansions PAS positive, Congo red negative and weakly positive for IgG. Given the above findings, the diagnosis was fibrillary glomerulonephritis. Glomerular lesions with organized deposits may exhibit syndromic and pathological overlap. For this reason it is important to initially discriminate between positive and negative Congo red deposits, using, in the latter case, transmission electron microscopy to distinguish between immuno-tactoid and fibrillary glomerulonephritis. This differentiation relies not only on ultrastructural features, but on different clinical characteristics. Unlike what happens with fibrillary glomerulonephritis, the immuno-tactoid shows a strong association with lymphoproliferative processes. PMID- 22057173 TI - [Vertigo and vertical nystagmus associated with intrathecal morphine administration and resolution by naloxone]. AB - Combined regional anesthesia is frequently used as a tool for management of postoperative pain. The profile of side effects of the opioids used via this route is similar to those occurring after systemic administration. The onset of vertigo with vertical nystagmus is an adverse effect rarely described after the use of intrathecal, epidural or intravenous morphine. We report the case of a patient who presented this complication in the postoperative period of a partial nephrectomy, after the administration of intrathecal morphine, with complete resolution by intravenous naloxone. PMID- 22057174 TI - [Schwannoma of the brachial plexus resembling a breast adenocarcinoma metastasis]. AB - Schwanomas originating from the brachial plexus, although rare, may be mistaken for another type of tumour. A 40 year-old woman, who had been treated years earlier for a breast adenocarcinoma, showed in the 5-year follow-up magnetic resonance examination a localized lesion in the right brachial plexus. The presumptive radiological diagnosis was a metastasis from the primary adenocarcinoma. Following surgical access via the right axilla, a well circumscribed mass in the brachial plexus was detected. Under intraoperative electrophysiological guidance, the lesion was observed to depend on the ulnar nerve and its complete resection was possible without compromising nerve function. Histological findings indicated a schwannoma thus ruling out the presence of metastasis. The postoperative development was uneventful and six years after surgery, the patient is to date tumour-free. To the best of our knowledge, this is the first report of a brachial plexus schwannoma arising from the ulnar branch. Intraoperative electrophysiological monitoring is essential for a good surgical outcome. PMID- 22057175 TI - [Interstitial lymphoid pneumonia associated with common variable immunodeficiency]. AB - The interstitial lymphoid pneumonia (LIP) is an uncommon disorder, described as non-neoplastic lung lymphoid tissue hyperplasia and classified as an interstitial lung disease. It has been described in association with HIV infection, autoimmune disorders, policlonal hypergammaglobulinemia and less frequently, with hypogammaglobulinemia. We report the case of a 66 year old female patient with a history of diabetes, Sjogren syndrome and hypertension. She was referred to our hospital due to a dry cough and dyspnea (FC II-III). The physical examination showed bilateral dry crackles and splenomegaly. Laboratory studies showed thrombocytopenia (50 000/ mm3) and hypogammaglobulinemia. A computed tomography thoracic scan showed interstitial bilateral basal lung infiltrates with small peribroncovascular nodules. A lung biopsy was made by thoracoscopy and reported LIP. Initial treatment consisted of oral methilprednisone, 40 mg daily, and once a month intravenous gammaglobulin 500 mg/kg, with good clinical and radiological response. A splenectomy was done due to persistent thrombocytopenia associated with hypersplenism, with good response of the platelets counts. No lymphoid clonal or other associated disease was detected. PMID- 22057176 TI - [Cryoglobulinemic nephropathy CD68 positive in monocytes/glomerular macrophages]. PMID- 22057177 TI - [Primary central nervous system lymphoma]. PMID- 22057178 TI - [Pathophysiology of shock. New perspectives]. AB - Metabolic activity can be down-regulated throughout the reduction of mitochondrial population. Lowering O2 demand in cardiogenic, hemorrhagic and septic shock is here examined through clinical observations and trials. A decrease in the availability of O will be followed by reductions in mitochondrial population and, therefore, in a decrease in O2 demand. This response may lessen or prevent the acquisition of an O2 debt; until now, cornerstone in the pathophysiology of shock. The cost of this adaptation is less energy production, and the resulting energy deficit has been linked to multiple organ failure (MOF), a complication of acute inflammatory processes and shock. MOF is better tolerated than anaerobic metabolism and is potentially reversible if the triggering causes are reversed and the energy level is re-established through mitochondrial biogenesis.Decoupling of mitochondrial oxidative phosphorylation occurs in both experimental models and in clinical septic shock. In critical patients this phenomenon may be detected by an inordinate increase in VO2 in response to a therapeutically increased DO. This hipermetabolic stage can be mistakenly interpreted as the repayment phase of an O2 debt. PMID- 22057179 TI - Melatonin in Chagas' disease. Possible therapeutic value. AB - Chagas' disease is a severe health problem in Latin America, causing approximately 50 000 deaths a year, with approximately 18 million infected people. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. The protective response against T. cruzi depends on both innate and acquired immunity involving macrophages, natural killer cells, T and B lymphocytes, and the production of proinflammatory Th-1 cytokines. In addition, an increased nitric oxide (NO) production in macrophages leading to effective microbicidal action is needed to control parasitemia. Melatonin is detectable in T. cruzi and may play a role in promoting infection whereas, when administered in high doses during the acute phase of T. cruzi infection, it can decrease parasitemia while reducing NO production. During chronic disease progression, the sustained oxidative stress concomitant to myocardial damage could be reduced by administering melatonin. It is hypothesized that the coordinated administration of a melatonin agonist like the MT1 /MT2 agonist ramelteon, that lacks antioxidant activity and may not affect NO production during the acute phase, and of melatonin in doses high enough to decrease oxidative damage, to preserve mitochondrial and to prevent cardiomyopathy during the chronic phase, could be a novel add-on treatment of Chagas' disease. PMID- 22057180 TI - [Impact factor, its variants and its influence in academic promotion]. AB - Bibliometrics is a set of methods used to study or measure texts and information. While bibliometric methods are most often used in the field of library and information science, bibliometrics variables have wide applications in other areas. One popular bibliometric variable is Garfield's Impact Factor (IF). IF is used to explore the impact of a given field, the impact of a set of researchers, or the impact of a particular paper. This variable is used to assess academic output and it is believed to affect adversely the traditional approach and assessment of scientific research. In our country, the members of the evaluation committees of intensive research institutions, e.g. the National Scientific and Technical Research Council (CONICET) use IF to assess the quality of research. This article revises the exponential growth of bibliometrics and attempts to expose the overall dissatisfaction with the analytical quality of IF. Such dissatisfaction is expressed in the number of investigations attempting to obtain a better variable of improved analytical quality. PMID- 22057181 TI - [The war against cancer]. PMID- 22057182 TI - [Unexpected pause: what is the mechanism ?]. PMID- 22057183 TI - [Clinical judicial syndrome]. PMID- 22057184 TI - [It's the patient, stupid !]. PMID- 22057185 TI - Enzyme responsive luminescent ruthenium(II) cephalosporin probe for intracellular imaging and photoinactivation of antibiotics resistant bacteria. AB - The Forster resonance energy transfer (FRET) based luminescent ruthenium(II) cephalosporin probe has been designed and synthesized, which can be selectively activated by endogenous beta-lactamases and thus provided a localized and specific intracellular luminescence imaging and photoinactivation of drug resistant bacterial pathogens. PMID- 22057186 TI - Dual anticancer activity in a single compound: visible-light-induced apoptosis by an antiangiogenic iridium complex. AB - A metal complex is identified in which the metal fulfills two independent functions: as a structural scaffold for the specific molecular recognition of protein kinases resulting in antiangiogenic properties, together with a visible light-induced photoreactivity triggering apopotosis in cancer cells. PMID- 22057187 TI - Efficacy of oxaliplatin-based chemotherapy in curatively resected colorectal cancer with liver metastasis. AB - OBJECTIVES: Although surgical resection alone has been validated as a standard treatment for patients with liver metastases from colorectal cancer, a high rate of recurrence is still an issue to be overcome. We aimed to assess the efficacy of adjuvant chemotherapy using an oxaliplatin-based regimen in patients who underwent hepatic and primary colorectal cancer resection. METHODS: Sixty patients who received oxaliplatin-based postoperative chemotherapy combined with curative resection of primary colorectal cancer and synchronous liver metastases between January 2000 and February 2008 were retrospectively reviewed. The Kaplan Meier method was used to estimate survival, and prognostic factors were evaluated with the log-rank test. RESULTS: Median overall survival (OS) was 62.8 months [95% confidence interval (CI) 44.1-81.3], and median relapse-free survival (RFS) was 32.8 months (95% CI 5.8-59.6). The 1-, 3- and 5-year survival rates were 95.0, 68.8 and 55.5%, respectively. The relapse-free interval and modality of liver resection were independently associated with OS. CONCLUSIONS: Oxaliplatin based adjuvant chemotherapy after radical resection resulted in increased OS and RFS with acceptable tolerability compared to surgery alone. However, it is not yet clear whether postoperative oxaliplatin-based chemotherapy improves outcome compared to patients treated with 5-fluorouracil plus leucovorin. PMID- 22057188 TI - The Na(+)/Ca(2+) exchanger NCKX4 governs termination and adaptation of the mammalian olfactory response. AB - Sensory perception requires accurate encoding of stimulus information by sensory receptor cells. We identified NCKX4, a potassium-dependent Na(+)/Ca(2+) exchanger, as being necessary for rapid response termination and proper adaptation of vertebrate olfactory sensory neurons (OSNs). Nckx4(-/-) (also known as Slc24a4) mouse OSNs displayed substantially prolonged responses and stronger adaptation. Single-cell electrophysiological analyses revealed that the majority of Na(+)-dependent Ca(2+) exchange in OSNs relevant to sensory transduction is a result of NCKX4 and that Nckx4(-/-) mouse OSNs are deficient in encoding action potentials on repeated stimulation. Olfactory-specific Nckx4(-/-) mice had lower body weights and a reduced ability to locate an odorous source. These results establish the role of NCKX4 in shaping olfactory responses and suggest that rapid response termination and proper adaptation of peripheral sensory receptor cells tune the sensory system for optimal perception. PMID- 22057189 TI - Polymodal activation of the endocannabinoid system in the extended amygdala. AB - The reason why neurons synthesize more than one endocannabinoid (eCB) and how this is involved in the regulation of synaptic plasticity in a single neuron is not known. We found that 2-arachidonoylglycerol (2-AG) and anandamide mediate different forms of plasticity in the extended amygdala of rats. Dendritic L-type Ca(2+) channels and the subsequent release of 2-AG acting on presynaptic CB1 receptors triggered retrograde short-term depression. Long-term depression was mediated by postsynaptic mGluR5-dependent release of anandamide acting on postsynaptic TRPV1 receptors. In contrast, 2-AG/CB1R-mediated retrograde signaling mediated both forms of plasticity in the striatum. These data illustrate how the eCB system can function as a polymodal signal integrator to allow the diversification of synaptic plasticity in a single neuron. PMID- 22057190 TI - Evolutionary differences in food preference rely on Gr64e, a receptor for glycerol. AB - Very little is known about how stimuli that are typically not rich in sugars, such as beer, trigger attractive gustatory responses in Drosophila. We identified a member of the gustatory receptor family, Gr64e, as a receptor that is required for feeding preference for beer and other sources that have fermenting yeast. We found that Gr64e is required for neuronal and behavioral responses to glycerol, an abundant component of growing yeast and fermentation products. Ectopic expression of Gr64e in an olfactory neuron conferred responsiveness to glycerol. We also found that Drosophila species that are predicted to carry pseudogenes of Gr64e had reduced glycerol sensitivity. Our results provide insight into the molecular mechanisms of feeding acceptance of yeast products and raise the possibility that Gr64e contributes to specific evolutionary variations in appetitive selectivity across Drosophila species. PMID- 22057191 TI - Cholinergic modulation of a specific memory function of prefrontal cortex. AB - Deficits in prefrontal cholinergic function are implicated in cognitive impairment in many neuropsychiatric diseases, but acetylcholine's specific role remains elusive. Rhesus monkeys with selective lesions of cholinergic input to prefrontal cortex (PFC) were unimpaired in tests of decision making and episodic memory that require intact PFC, but were severely impaired on a spatial working memory task. These observations are consistent with a specific role for prefrontal acetylcholine in working memory. PMID- 22057192 TI - Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF. AB - Stress affects various forms of cognition. We found that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task. Ventromedial prefrontal cortex (vmPFC) lesions mimicked the effect of stress, whereas orbitofrontal and dorsolateral striatal lesions impaired reversal. Stress facilitation of reversal was prevented by BDNF infusion into the vmPFC. These findings suggest a mechanism by which stress-induced vmPFC dysfunction disinhibits learning by alternate (for example, striatal) systems. PMID- 22057193 TI - Orientation tuning of cytochrome oxidase patches in macaque primary visual cortex. AB - The abundant concentration of cytochrome oxidase in patches or blobs of primate striate cortex has never been explained. Patches are thought to contain unoriented, color-opponent neurons. Lacking orientation selectivity, these cells might endow patches with high metabolic activity because they respond to all contours in visual scenes. To test this idea, we measured orientation tuning in layer 2/3 of macaque cortical area V1 using acutely implanted 100-electrode arrays. Each electrode recording site was identified and assigned to the patch or interpatch compartment. The mean orientation bandwidth of cells was 28.4 degrees in patches and 25.8 degrees in interpatches. Neurons in patches were indeed less orientation selective, but the difference was subtle, indicating that the processing of form and color is not strictly segregated in V1. The most conspicuous finding was that patch cells had a 49% greater overall firing rate. This global difference in neuronal responsiveness, rather than an absence of orientation tuning, may account for the rich mitochondrial enzyme activity that defines patches. PMID- 22057194 TI - Periodontitis and diabetes: a two-way relationship. AB - Periodontitis is a common chronic inflammatory disease characterised by destruction of the supporting structures of the teeth (the periodontal ligament and alveolar bone). It is highly prevalent (severe periodontitis affects 10-15% of adults) and has multiple negative impacts on quality of life. Epidemiological data confirm that diabetes is a major risk factor for periodontitis; susceptibility to periodontitis is increased by approximately threefold in people with diabetes. There is a clear relationship between degree of hyperglycaemia and severity of periodontitis. The mechanisms that underpin the links between these two conditions are not completely understood, but involve aspects of immune functioning, neutrophil activity, and cytokine biology. There is emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control. Incidences of macroalbuminuria and end-stage renal disease are increased twofold and threefold, respectively, in diabetic individuals who also have severe periodontitis compared to diabetic individuals without severe periodontitis. Furthermore, the risk of cardiorenal mortality (ischaemic heart disease and diabetic nephropathy combined) is three times higher in diabetic people with severe periodontitis than in diabetic people without severe periodontitis. Treatment of periodontitis is associated with HbA(1c) reductions of approximately 0.4%. Oral and periodontal health should be promoted as integral components of diabetes management. PMID- 22057195 TI - Early adulthood television viewing and cardiometabolic risk profiles in early middle age: results from a population, prospective cohort study. AB - AIMS/HYPOTHESIS: Little research has been done on the long-term longitudinal associations between markers of sedentary behaviour and health risks. We hypothesised that television (TV) viewing in early to mid-adulthood predicts an adverse cardiometabolic risk factor profile in middle age independently of participation in physical activity. METHODS: We used prospective data from 5,972 (2,947 men) participants of the 1958 British Birth Cohort study. TV viewing and exercise frequency were obtained at age 23 years. Daily TV viewing and weekly moderate to vigorous physical activity were assessed at age 44 years, as well as HbA(1c), triacylglycerol, total and HDL-cholesterol, systolic and diastolic blood pressure, and waist circumference. We used generalised linear models and multiple linear regression to examine the associations between TV viewing at age 23 years and the cardiometabolic risk markers (including a clustered cardiometabolic risk score) at 44 years, while adjusting for sex, exercise participation and TV viewing at age 44 years, and other potential confounders. RESULTS: In the multivariable models, TV viewing frequency at age 23 years showed positive associations with C-reactive protein (generalised linear model change 12.6%, 95% CI 3.5, 22.8; p = 0.005), fibrinogen (change 1.8%, 95% CI 0.3, 3.3; p = 0.020), waist circumference (coefficient 1.17, 95% CI 0.32, 2.01; p = 0.004), systolic (coefficient 1.44, 95% CI 0.33, 2.54; p = 0.019) and diastolic (coefficient 0.75, 95% CI -0.01, 1.51; p = 0.053) blood pressure, and clustered cardiometabolic risk score (men only, coefficient 0.06, 95% CI 0.01, 0.11; p = 0.038). Adjustments for baseline (age 23 years) BMI attenuated these associations towards null. CONCLUSIONS/INTERPRETATION: TV viewing habits in early adulthood are associated with adverse cardiometabolic profiles in early middle adulthood that are independent of TV viewing habits and physical activity in middle age, but not independent of BMI in early adulthood. PMID- 22057196 TI - Five-year follow-up of a cohort of people with their first diabetic foot ulcer: the persistent effect of depression on mortality. AB - AIMS/HYPOTHESIS: Depressive disorders are associated with mortality within 18 months of presentation of diabetic foot ulcers (DFU). The main aim of this study was to determine whether depressive disorder is still associated with increased mortality in people with their first foot ulcer at 5 years. METHODS: This is a 5 year follow-up of a cohort of 253 patients presenting with their first DFU. At baseline, the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) 2.1 was used to define those who met DSM-IV (Diagnostic and Statistical Manual 4th edition) criteria for depressive disorder. Cox regression analysis controlled for potential covariates: age, sex, marital status, socioeconomic status, smoking, mean HbA(1c), diabetes complications and ulcer severity. The main outcome was mortality at 5 years. RESULTS: The prevalence of DSM-IV depressive disorder at baseline was 32.2% (n = 82). There were 92 (36.4%) deaths over the 5 years of follow-up. In the Cox regression (n = 246), after adjusting for covariates, baseline DSM-IV depressive disorder was significantly associated with a twofold increased risk of mortality for any depressive episode (HR 2.09, 95% CI 1.34, 3.25), minor (HR 1.93, 95% CI 1.00, 3.74) or major depressive disorders (HR 2.18, 95% CI 1.31, 3.65), compared with patients who were not depressed. CONCLUSIONS/INTERPRETATION: Depression is associated with a persistent twofold increased risk of mortality in people with their first DFU at 5 years. PMID- 22057197 TI - Building muscle, browning fat and preventing obesity by inhibiting myostatin. AB - The obesity epidemic is an overwhelming global health concern. Interventions to improve body weight and composition aim to restore balance between nutrient intake and energy expenditure. Myostatin, a powerful negative regulator of skeletal muscle mass, has emerged as a potential therapeutic target for obesity and type 2 diabetes mellitus because of the prominent role skeletal muscle plays in metabolic rate and insulin-mediated glucose disposal. In fact, inhibition of myostatin by genetic manipulation or pharmacological means leads to a hypermuscular and very lean build in mice. The resistance of myostatin-null mice to diet-induced obesity, fat mass accumulation and metabolic dysfunction has been presumed to be a result of their large skeletal muscle mass; however, in this issue of Diabetologia, Zhang et al. (doi: 10.1007/s00125-011-2304-4 ) provide evidence that myostatin inhibition also significantly impacts the phenotype of white adipose tissue (WAT). The authors reveal elevated expression of key metabolic genes of fatty acid transport and oxidation and, intriguingly, the presence of brown adipose tissue-like cells in WAT of myostatin-null mice. They also show that pharmacological inhibition of myostatin replicates several of the protective benefits conveyed by its genetic inactivation. Herein, these data, areas in need of further investigation and the evidence that implicates myostatin as a target for obesity and type 2 diabetes mellitus are discussed. PMID- 22057198 TI - Usefulness of ice massage in triggering the swallow reflex. AB - In Japan, ice massage is widely used as the prefeeding technique to facilitate dry swallowing, to improve swallowing apraxia for initiating the swallowing action, and in daily swallowing training. In a crossover study, we evaluated the usefulness of ice massage for eliciting the swallowing response. The subjects were 24 dysphagic patients with stroke and cerebrovascular disease. We measured the latency between the command of dry swallowing and the triggering of the swallow reflex by videofluoroscopic examination of swallowing, with and without ice massage. When a subject could not swallow all the 4 trials we recorded whether he or she could swallow or not. And we counted how many times he or she could swallow with and without ice massage. Our results suggest that ice massage significantly shortened the latency to triggering of the swallow reflex and often initiated swallowing even in those subjects who could not swallow without the massage. These results demonstrate that ice massage has an immediate effect on triggering of the swallow reflex. The effect of ice massage was especially remarkable in the 15 subjects who had supranuclear lesions compared with the subjects with nuclear lesions. Thus, ice massage could activate the damaged supranuclear tract and/or the normal nucleus and subnuclear tract for swallowing. Ice massage has proven useful in many clinical dysphagia training sessions. PMID- 22057199 TI - Adults with reading disabilities: converting a meta-analysis to practice. AB - This article reviews the results of a meta-analysis of the experimental published literature that compares the academic, cognitive, and behavioral performance of adults with reading disabilities (RD) with average achieving adult readers. The meta-analysis shows that deficits independent of the classification measures emerged for adults with RD on measures of vocabulary, math, spelling, and specific cognitive process related to naming speed, phonological processing, and verbal memory. The results also showed that adults with high verbal IQs (scores > 100) but low word recognition standard scores (< 90) yielded greater deficits related to their average reading counterparts when compared to studies that included adults with RD with verbal IQ and reading scores in the same low range. Implications of the findings related to assessment and intervention are discussed. PMID- 22057200 TI - The speed of articulatory movements involved in speech production in children with dyslexia. AB - A group of children with dyslexia (mean ages 9 and 14 years) was studied, together with group of children without dyslexia matched for age. Participants were monolingual native speakers of the Bosnian language with transparent orthography. In total, the diagnostic tests were performed with 41 children with dyslexia and 41 nondyslexic children. The participants were asked to produce monosyllables, /pa/, /ta/, and /ka/, and the trisyllable /pataka/, as fast as possible. Analysis was undertaken in four ways: (1) time of occlusion duration for plosives (duration of stop), (2) voice onset time for plosives, (3) diadochokinetic rate--articulators rate measured by pronunciation of monosyllables and the trisyllable, and (4) time of moving articulators from one gesture to another-time of interval length (from the explosion of one plosive to the start of the explosion of another plosive). The results suggest that children with dyslexia have significant problems with the speed of articulatory movements involved in speech production. PMID- 22057201 TI - The identification and performance of gifted students with learning disability diagnoses: a quantitative synthesis. AB - Much has been written about gifted students with learning disabilities, but there have been few large-scale empirical investigations, and the concept has proven controversial. The authors reviewed the available empirical literature on these students, focusing on (a) the criteria by which the students were identified and (b) the students' performance on standardized tests of ability and achievement. In addition, the test scores of these students were aggregated to determine typical performance levels. A total of 46 empirical articles were reviewed, and major findings included wide variability in identification criteria across studies, frequent reliance on dubious methods of learning disability identification, and a lack of academic impairment among the identified students. Implications for the "gifted/LD" category are discussed. PMID- 22057202 TI - Cobalt oxide polymorph growth on electrostatic self-assembled nanoparticle arrays for dually tunable nano-textures. AB - We report on a method for surface nano-texturing on a plastic substrate. Nano objects with a silica nanoparticle core and a textured cobalt oxide crown are created with selectable density on the plastic substrate. The resulting dual morphology is easily tuned over large areas, either by changing the parameters directing nanoparticle deposition through electrostatic self-arrangement for nano object density control, or the parameter directing cobalt oxide deposition for shape control. The entire process takes place at room temperature, with no chemicals harmful to the plastic substrate. The ready modulation of the dual morphology is used to control the wettability properties of the plastic film, which is covered by nano-objects. PMID- 22057203 TI - Polymyalgia rheumatica and the risk of stroke: a three-year follow-up study. AB - BACKGROUND: Polymyalgia rheumatica (PMR) is a relatively common rheumatic disease, particularly in the elderly. Vasculitis is associated with PMR and theoretically makes such patients susceptible to vascular events such as stroke. This study aims to explore the frequency and risk of stroke among patients with PMR through a population-based case-controlled study. METHODS: The study included 781 patients with PMR from the Taiwan Longitudinal Health Insurance Database between 2001 and 2005. We randomly extracted 3,905 other patients, matched with the study group in terms of sex and age, as a control population. Each subject was individually tracked for a three-year period to identify those who had strokes. Stratified Cox proportional hazard regression was employed to evaluate the risk of stroke, after adjusting for socio-demographic characteristics and comorbidities. RESULTS: We found that 386 out of 4,686 sampled patients (8.24%) had stroke during the three-year follow-up period, including 113 patients with PMR (14.47% of the PMR group) and 273 controls (6.98% of the control group). The stratified Cox proportional hazard regression showed that the adjusted hazard ratio of stroke for patients with PMR was 2.09 times that of controls (95% CI = 1.63-2.66, p <0.001), after adjusting for socio-demographic characteristics and comorbidities. CONCLUSIONS: PMR was associated with a significantly higher risk of stroke in the three-year follow-up period. Physicians should be aware of this potential association in clinical settings. PMID- 22057204 TI - Inhibition of calcium oxalate crystal deposition on kidneys of urolithiatic rats by Hibiscus sabdariffa L. extract. AB - The present study aims at systematic evaluation of the calyces of Hibiscus sabdariffa to establish its scientific validity for anti-urolithiatic property using ethylene glycol-induced hyperoxaluria model in male albino rats. Administration of a mixture of 0.75% ethylene glycol and 2% ammonium chloride resulted in hyperoxaluria as well as increased renal excretion of calcium and phosphate. The decrease in the serum calcium concentration indicates an increased calcium oxalate formation. Supplementation of aqueous extract of H. sabdariffa at different doses (250, 500 and 750 mg/kg body weight) significantly lowered the deposition of stone-forming constituents in the kidneys and serum of urolithiatic rats. These findings have been confirmed through histological investigations. Results of in vivo genotoxicity testing showed no significant chromosomal aberrations in the bone marrow cells of ethylene glycol-induced rats. The plant extracts at the doses investigated induced neither toxic nor lethal effects and are safe. It can be concluded that the calyces of H. sabdariffa are endowed with anti-urolithiatic activity and do not have genotoxic effects. Thus, it can be introduced in clinical practices and medicine in the form of orally administered syrup after further investigations and clinical trials. PMID- 22057205 TI - Stereotactic localisation system: a modified puncture technique for percutaneous nephrolithotomy. AB - The objective of the study was to establish and evaluate a modified puncture and dilation technique-"stereotaxic localisation" system-and the corresponding instruments for percutaneous nephrostomy. Four hundred patients were randomised to the intervention group (200 cases, stereotaxic location puncture and dilation procedures) and the traditional group (200 cases, traditional procedure) under X ray guidance. In the modified intervention system, the distance and horizontal angle of the puncture pathway between the puncture point and the target site were calculated accurately. The time for punctures, time with X-ray exposure and operation, success rate of each puncture to access the target, number of patients requiring blood transfusion, stone clearance, drops of haemoglobin and days of hospital stay were compared between the two groups. In the traditional and intervention groups, the time for puncture was 17 and 7 min, respectively; the X ray exposure time was 9.1 and 1.3 min; the cases requiring blood transfusion were 9 and 5; and the success rates for each puncture to access the target were 42.9 and 88.0%, all with statistical difference (p < 0.01). The other outcomes and complications revealed similar trends. The stereotaxic localisation system for puncture is statistically better than the traditional procedure used in this study. The stereotaxic localisation system in this study is safer and more accurate, and provides easier access to the target with less bleeding and reduced exposure to X-ray compared to the traditional puncture and dilation procedures of percutaneous nephrostomy. PMID- 22057206 TI - Ureteroscopic retrograde intrarenal surgery after previous open renal stone surgery: initial experience. AB - The management of renal calculi following previous open surgery represents a challenge for urologists. The aim of this study is to evaluate the outcomes and safety of ureteroscopic laser retrograde intrarenal surgery (RIRS) for renal calculi following prior open renal surgery. The charts of 53 patients who underwent RIRS for renal calculi following prior open surgery for urolithiasis were reviewed. Both flexible and semi-rigid ureteroscopes were utilized together with holmium: YAG laser for stone disintegration. Intravenous urography, computed tomography (CT) and ultrasound were used to evaluate the patient, perioperatively. Stone size ranged from 5 to 32 mm (mean 14.3 mm). The mean operative time was 86 min (20-130). The overall stone-free rate was 92.4%. The overall stone-free rates after one and two-procedures were 79.2% (42 cases) and 92.4% (49 cases), respectively. Four patients (7.5%) had larger residual fragments, 2 (3.8%) of them underwent SWL, and 2 (3.8%) cases were followed up conservatively. Major complications were reported in two patients (3.8%). Stone analysis revealed calcium oxalate in 39 patients, uric acid in 5, calcium phosphate in 4, struvite in 3, and cystine in 2 cases. Ureteroscopic retrograde intrarenal surgery for renal calculi following prior open renal surgery was a minimally invasive, safe procedure with a high success rate. It is a viable alternative for PNL in managing recurrent renal calculi efficiently. PMID- 22057207 TI - Palliative services, forgotten issue in postnuclear accident crisis. PMID- 22057208 TI - Pediatric palliative care instruction for residents: an introduction to IPPC. AB - A 1-day training event for pediatric residents with interdisciplinary staff was held, which was modeled after the Initiative for Pediatric Palliative Care (IPPC). Training included relational communication, cultural humility, pain symptom management, family-centered care, team problem solving, and strategic planning using didactic, small group, and plenary platforms. Two bereaved parents were co-learners and trainers. Twenty-six interdisciplinary staff participated. A positive impact was measured in new knowledge gained, value in collaborative learning with health care professionals and families, and ability to work with professionals outside participants' own unit. Confidence to advocate for improved pediatric palliative care was also noted. The IPPC curriculum is easily adapted for resident education. Incorporating family members as co-learners and teachers is valuable. Advocacy for pediatric palliative care may follow this type of experience. PMID- 22057209 TI - Quality of life in patients with advanced lung cancer treated at home and at a palliative care unit. AB - BACKGROUND: To assess quality of life (QOL) in patients with advanced lung cancer. PATIENTS AND METHODS: A prospective study of 78 patients cared at home and at a palliative care unit (PCU) with 2 QOL assessments was conducted. RESULTS: Fifty patients completed the study. In the EORTC QLQ-C30 role, cognitive, social functioning, global QOL, fatigue, pain, dyspnea, and appetite deteriorated; nausea/vomiting improved; dyspnea was more intense in the case of in-home patients. In the EORTC QLQ-LC13 hemoptysis improved; pain in other parts was more intense in the PCU patients. Pain (Visual Analogue scale) was more intense in the PCU patients; the level of activity (Karnofsky) decreased in the case of patients treated at home. CONCLUSIONS: QOL deteriorated with few differences between home and the PCU patients. PMID- 22057210 TI - Symptom prevalence in the last days of life in Germany: the role of place of death. AB - Investigations have shown that symptom prevalence varies according to the place of death. We sought to assess the symptom prevalence of chronically ill people in Germany and how this prevalence differs depending on the place of death. We sent questionnaires to 5000 bereaved people in Rhineland-Palatinate (Germany), whose relatives died between May 25 and August 24, 2008. In all, 3832 questionnaires were delivered and 1378 completed (response 36.0%). Most decedents had moderate to-severe weakness (94.5%), fatigue (93.5%), need for help in daily activities (87.9%), and appetite loss (87.4%). Pain and dyspnea were most severe in hospitals; fatigue, confusion/disorientation, and problems with wound care in nursing homes; and need for help in daily activities and overburden of family at home. Associations persisted after adjusting for potential confounders. PMID- 22057211 TI - New insights into the spliceosome by single molecule fluorescence microscopy. AB - Splicing is an essential eukaryotic process in which introns are excised from precursors to messenger RNAs and exons ligated together. This reaction is catalyzed by a multi-MegaDalton machine called the spliceosome, composed of 5 small nuclear RNAs (snRNAs) and a core set of ~100 proteins minimally required for activity. Because of the spliceosome's size, its low abundance in cellular extracts, and its highly dynamic assembly pathway, analysis of the kinetics of splicing and the conformational rearrangements occurring during spliceosome assembly and disassembly has proven extraordinarily challenging. Here, we review recent progress in combining chemical biology methodologies with single molecule fluorescence techniques to provide a window into splicing in real time. These methods complement ensemble measurements of splicing in vivo and in vitro to facilitate kinetic dissection of pre-mRNA splicing. PMID- 22057212 TI - Single-molecule analysis of telomerase structure and function. AB - The telomerase ribonucleoprotein is a specialized reverse transcriptase required to maintain protective chromosome end-capping structures called telomeres. In most cells, telomerase is not active and the natural shortening of telomeres with each round of DNA replication ultimately triggers cell growth arrest. In contrast, the presence of telomerase confers a high level of renewal capacity upon rapidly dividing cells. Telomerase is aberrantly activated in 90% of human cancers and thus represents an important target for anticancer therapeutics. However, the naturally low abundance of telomerase has hampered efforts to obtain high-resolution models for telomerase structure and function. To circumvent these challenges, single-molecule techniques have recently been employed to investigate telomerase assembly, structure, and catalysis. PMID- 22057214 TI - Standardisation of liver MDCT by tracking liver parenchyma enhancement to trigger imaging. AB - OBJECTIVE: To assess parenchymal bolus-triggering in terms of liver enhancement, lesion-to-liver conspicuity and inter-image variability across serial follow-up MDCTs. METHODS: We reviewed MDCTs of 50 patients with hepatic metastases who had a baseline CT and two follow-up examinations. In 25 consecutive patients CT data acquisition was initiated by liver parenchyma triggering at a 50-HU enhancement threshold. In a matched control group, imaging was performed with an empirical delay of 65 s. CT attenuation values were assessed in vessels, liver parenchyma and metastasis. Target lesions were classified according to five enhancement patterns. RESULTS: Compared with the control group, liver enhancement was significantly higher with parenchyma triggering (59.8 +/- 7.6 HU vs. 48.8 +/- 11.2 HU, P = 0.0002). The same was true for conspicuity (liver parenchyma - lesion attenuation) of hypo-enhancing lesions (72.2 +/- 15.9 HU vs. 52.7 +/- 19.4 HU, P = 0.0006). Liver triggering was associated with reduced variability for liver enhancement among different patients (P = 0.035) and across serial follow up examinations in individual patients (P < 0.0001). The number of patients presenting with uniform lesion enhancement pattern across serial examinations was significantly higher in the triggered group (20 vs. 11; P = 0.018). CONCLUSION: Liver parenchyma triggering provides superior lesion conspicuity and improves standardisation of image quality across follow-up examinations with greater uniformity of enhancement patterns. KEY POINTS: Liver parenchyma tracking improves liver enhancement and lesion-to-liver conspicuity in abdominal CT. In serial CT studies this technique reduces variability of conspicuity and enhancement patterns. Higher liver-to-lesion conspicuity is a prerequisite for reliable detection of liver lesions. Stabilisation of enhancement permits more accurate follow-up of oncology patients. PMID- 22057216 TI - Influence of GRIA1, GRIA2 and GRIA4 polymorphisms on diagnosis and response to treatment in patients with major depressive disorder. AB - The present study is aimed to exploring whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with major depressive disorder (MDD) and whether they could predict clinical outcomes in Korean in-patients, respectively, treated with antidepressants. One hundred forty five (145) patients with MDD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures, including the Montgomery-Asberg Depression Rating Scale (MADRS) for patients with MDD, were recorded. No association was observed between alleles, genotypes and haplotypes under investigation and clinical and demographical variables. As a secondary finding, a marginal association was observed between rs4302506 and rs4403097 alleles within GRIA2 and age of onset in patients with MDD. Our findings provide evidence for a possible association between rs4302506 and rs4403097 SNPs and age of onset in patients with MDD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions. PMID- 22057217 TI - How can grafted breast cancer models be optimized? AB - Breast cancer is the most frequent spontaneous malignancy diagnosed in women and is characterized by a broad histological diversity. Progression of the disease has a metastasizing trend and can be resistant to hormonal and chemotherapy. Animal models have provided some understanding of these features and have allowed new treatments to be proposed. However, these models need to be revised because they have some limitations in predicting the clinical efficacy of new therapies. In this review, we discuss the biological criteria to be taken into account for a realistic animal model of breast cancer graft (tumor implantation site, animal immune status, histological diversity, modern imaging). We emphasize the need for more stringent monitoring criteria, and suggest adopting the human RECIST (Response Evaluation Criteria in Solid Tumors) criteria to evaluate treatments in animal models. PMID- 22057218 TI - Development of inhibitors in haemophilia. Ongoing epidemiological study. AB - A number of 513 consecutive patients (494-haemophilia A and 19-haemophilia B) from eight haemophilia treatment centers have been investigated with Bethesda assay for the presence of factor VIII or IX inhibitors. The overall prevalence of inhibitors was 15.20%, 18.48% in severe, 5.60% in moderate and 12.24% in mild forms. The prevalence was higher than reported in most of the western countries. The age at start of substitution (p = 0.9775), the frequent switching of factor concentrates (p = 0.8931) were not relevant factors for the development of inhibitors. It is worth to be mentioned the unexpectedly occurrence of inhibitors in prior inhibitor negative (6/72) patients (during surgical interventions) probably due to their previous scarce substitution, occurrence which seems not being connected with the continuous infusion modality of factor VIII administration (p = 0.8341). In controversial situations, in the field of low titer (<= 1 BU/ml) inhibitors for a reliable interpretation of the results the performance of recovery index and half-life time assessment of FVIII/IX was undertaken. PMID- 22057219 TI - Urinary tract infection following kidney transplantation: frequency, risk factors and graft function. AB - The aim of this study was to determine the proportion of children who develop urinary tract infection (UTI) after kidney transplantation (KTx) and to identify the factors associated with UTI and its impact on graft function. To this end, we undertook a chart review of children who underwent KTx at Red Cross Children's Hospital between January 2003 and December 2009 and were followed-up for at least 6 months after transplantation. Sixty-two children (53.2% males) were followed-up for a mean (standard deviation) period of 36.9 (19.7) months. Mean age at transplantation was 10.0 (4.6) years. Twenty-five (40.3%) children had 89 UTI episodes during the study period, equivalent to 0.94 UTI episodes per one patient year of follow-up. Acute pyelonephritis occurred in 17 (27.4%) children; another 17 (27.4%) had multiple post-KTx UTI. Klebsiella (40.0%) and Escherichia (28.0%) were the commonest organisms. Those with post-KTx UTI were, at transplantation, younger (8.3 vs. 11.2 years; p = 0.017), had lower urinary tract abnormality (LUTA) (13 vs. 1; p = 0.000) and had pre-KTx UTI (13 vs. 5; p = 0.001). Multivariate analysis revealed that only age <5 years at transplantation and LUTA remained significant and that UTI KTx was not associated with worsening graft function. UTI is common after post-KTx. Among our patient cohort, younger age and LUTA were risk factors, but UTI did not affect graft function. PMID- 22057220 TI - Automatic analysis of EMG during clonus. AB - Clonus can disrupt daily activities after spinal cord injury. Here an algorithm was developed to automatically detect contractions during clonus in 24h electromyographic (EMG) records. Filters were created by non-linearly scaling a Mother (Morlet) wavelet to envelope the EMG using different frequency bands. The envelope for the intermediate band followed the EMG best (74.8-193.9 Hz). Threshold and time constraints were used to reduce the envelope peaks to one per contraction. Energy in the EMG was measured 50 ms either side of each envelope (contraction) peak. Energy values at 5% and 95% maximal defined EMG start and end time, respectively. The algorithm was as good as a person at identifying contractions during clonus (p=0.946, n=31 spasms, 7 subjects with cervical spinal cord injury), and marking start and end times to determine clonus frequency (intra class correlation coefficient, alpha: 0.949), contraction intensity using root mean square EMG (alpha: 0.997) and EMG duration (alpha: 0.852). On average the algorithm was 574 times faster than manual analysis performed independently by two people (p <= 0.001). This algorithm is an important tool for characterization of clonus in long-term EMG records. PMID- 22057221 TI - Histological and biochemical findings in membranous cataract. AB - BACKGROUND: In this report we present a patient with unilateral membranous cataract and describe the histological and biochemical findings accompanying this rare condition. METHODS: The patient underwent an uneventful cataract extraction. Aqueous humor (20 MUl) was aspirated from the anterior chamber intraoperatively and processed for fibroblast growth factor (FGF) and epidermal growth factor (EGF) using an immunoassay method (ELISA). The lens material was subjected to histological examination. RESULTS: The patient had increased levels of FGF and EGF in the aqueous humor, as measured by ELISA. Histological examination of the lens material showed a marked fibrous metaplasia and thickening of the anterior lens capsule, while the lens epithelial cells were transformed to active myofibroblasts which generated a fibrous matrix of collagen lamellae. Unfortunately, visual function was not restored postoperatively due to underlying amblyopia. CONCLUSIONS: Our histological and biochemical findings suggest that FGF and EGF may play a key role in the formation of membranous cataract, and therefore their impact on lens physiology should be further investigated. PMID- 22057222 TI - A controlled anion exchange strategy to synthesize Bi2S3 nanocrystals/BiOCl hybrid architectures with efficient visible light photoactivity. AB - Bi(2)S(3) nanocrystals/BiOCl hybrid architectures with tunable band gaps were synthesized by a controlled anion exchange approach and they displayed highly efficient visible light photoactivities, which is associated with suitable energetics and structural topotactic relationship that can benefit the interfacial charge transfer. PMID- 22057224 TI - Visible-light photocurrent response of TiO2-polyheptazine hybrids: evidence for interfacial charge-transfer absorption. AB - We investigated photoelectrodes based on TiO(2)-polyheptazine hybrid materials. Since both TiO(2) and polyheptazine are extremely chemically stable, these materials are highly promising candidates for fabrication of photoanodes for water photooxidation. The properties of the hybrids were experimentally determined by a careful analysis of optical absorption spectra, luminescence properties and photoelectrochemical measurements, and corroborated by quantum chemical calculations. We provide for the first time clear experimental evidence for the formation of an interfacial charge-transfer complex between polyheptazine (donor) and TiO(2) (acceptor), which is responsible for a significant red shift of absorption and photocurrent response of the hybrid as compared to both of the single components. The direct optical charge transfer from the HOMO of polyheptazine to the conduction band edge of TiO(2) gives rise to an absorption band centered at 2.3 eV (540 nm). The estimated potential of photogenerated holes (+1.7 V vs. NHE, pH 7) allows for photooxidation of water (+0.82 V vs. NHE, pH 7) as evidenced by visible light-driven (lambda > 420 nm) evolution of dioxygen on hybrid electrodes modified with IrO(2) nanoparticles as a co-catalyst. The quantum-chemical simulations demonstrate that the TiO(2)-polyheptazine interface is a complex and flexible system energetically favorable for proton-transfer processes required for water oxidation. Apart from water splitting, this type of hybrid materials may also find further applications in a broader research area of solar energy conversion and photo-responsive devices. PMID- 22057223 TI - An online resource of digital stories about cancer genetics: qualitative study of patient preferences and information needs. AB - BACKGROUND: The Cancer Genetics Service for Wales (CGSW) was established in 1998 as an all-Wales service for individuals with concerns about their family history of cancer. CGSW offers a range of services such as risk assessment, genetic counseling, and genetic testing. Individuals referred to cancer genetics services often have unmet information and support needs, and they value access to practical and experiential information from other patients and health professionals. As a result of the lifelong nature of genetic conditions, a fundamental challenge is to meet the ongoing needs of these patients by providing easily accessible and reliable information. OBJECTIVES: Our aims were to explore how the long-term information and support needs of CGSW patients could be met and to assess whether an online bank of digital stories about cancer genetics would be acceptable to patients. METHODS: In 2009, CGSW organized patient panels across Wales. During these events, 169 patients were asked for their feedback about a potential online resource of digital stories from CGSW patients and staff. A total of 75 patients registered to take part in the project and 23 people from across Wales agreed to share their story. All participants took part in a follow up interview. RESULTS: Patient preferences for an online collection of cancer genetics stories were collected at the patient panels. Key topics to be covered by the stories were identified, and this feedback informed the development of the website to ensure that patients' needs would be met. The 23 patient storytellers were aged between 28 and 75 years, and 19 were female. The digital stories reflect patients' experiences within CGSW and the implications of living with or at risk of cancer. Follow-up interviews with patient storytellers showed that they shared their experiences as a means of helping other patients and to increase understanding of the cancer genetics service. Digital stories were also collected from 12 members of staff working at CGSW. The digital stories provide reliable and easily accessible information about cancer genetics and are hosted on the StoryBank website (www.cancergeneticsstorybank.co.uk). CONCLUSIONS: The Internet is one mechanism through which the long-term information and support needs of cancer genetics patients can be met. The StoryBank is one of the first places where patient and staff stories have been allied to every aspect of a patient pathway through a service and provides patients with an experiential perspective of the cancer genetics "journey." The StoryBank was developed in direct response to patient feedback and is an innovative example of patient involvement in service development. The stories are a useful resource for newly referred patients, current patients, the general public, and health care professionals. PMID- 22057225 TI - Progression from mild to pronounced MCI is not associated with cerebrospinal fluid biomarker deviations. AB - BACKGROUND/AIM: Detection of cerebrospinal fluid (CSF) biomarker deviations improve prediction of progression from mild cognitive impairment (MCI) to dementia. However, it is not settled whether the same pattern exists in patients progressing from very mild to more pronounced MCI. Given that neurodegenerative processes occur very early in the disease course, we also expected to find biomarker deviations in these patients. METHODS: A total of 246 memory clinic patients with non-progressive (n = 161), progressive (n = 19), or converting (n = 66) MCI, 67 with stable dementia, and 80 controls were followed for 24 months. At baseline, CSF total tau (T-tau), beta-amyloid 1-42 (Abeta42) and the light subunit of neurofilament protein (NFL) were determined. RESULTS: Patients with converting MCI and stable dementia had lower CSF Abeta42 concentrations and higher T-tau concentrations and NFL in comparison with controls and non progressive/progressive MCI (p < 0.0005). No differences were found between progressive and non-progressive MCI. CONCLUSION: As expected, biomarker deviations predicted progression from MCI to dementia. Contrary to our hypothesis, progression from very mild MCI to more pronounced MCI was not reflected by biomarker deviations. The results suggest that the measured biomarkers are not early disease markers, or alternatively Alzheimer or vascular pathology is not the underlying cause in this patient group. PMID- 22057226 TI - Characteristics of polycyclic aromatic hydrocarbon emissions of particles of various sizes from smoldering incense. AB - Release of polycyclic aromatic hydrocarbons (PAHs) in particles of various sizes from smoldering incenses was determined. Among the three types of incense investigated, yielding the total PAH emission rate and factor ranges for PM0.25 were 2,139.7-6,595.6 ng/h and 1,762.2-8,094.9 ng/g, respectively. The PM0.25/PM2.5 ratio of total PAH emission factors and rates from smoldering three incenses was greater than 0.92. This study shows that total particle PAH emission rates and factors were mainly <0.25 MUm. Furthermore, the total toxic equivalency emission rates and factors of PAHs for PM0.25 were 241.3-469.7 and 198.8-576.2 ng/g from the three smoldering incenses. The benzo[a]pyrene accounted for 65.2% 68.0% of the total toxic equivalency emission factor of PM2.5 for the three incenses. Experimental results clearly indicate that the PAH emission rates and factors were influenced significantly by incense composition, including carbon and hydrogen content. The study concludes that smoldering incense with low atomic hydrogen/carbon ratios minimized the production of total polycyclic aromatic hydrocarbons of both PM2.5 and PM0.25. PMID- 22057227 TI - Guiana dolphins (Sotalia guianensis, Van Beneden 1864) as indicators of the bioaccumulation of total mercury along the coast of Rio de Janeiro state, Southeastern Brazil. AB - Total mercury (Hg) was determined in muscle tissue of 20 Guiana dolphins stranded along the coast of Rio de Janeiro state, Brazil, with a mean of 1.07 MUg/g wet weight. Mercury concentrations were positively related to body length, possibly related to the capacity of the dolphins to bioaccumulate this element throughout life. The Hg concentrations were not significantly different between males and females, although females (1.08 MUg/g) showed slightly higher levels than males (1.04 MUg/g). Concentrations were low when compared to results of studies carried out with small cetaceans in the Northern Hemisphere, and with previous studies in the Southeastern Brazil. PMID- 22057228 TI - Total mercury levels in selected tissues of some marine crustaceans from Persian Gulf, Iran: variations related to length, weight and sex. AB - Much of the variation in trace metal tissue concentrations in marine invertebrates has been attributed to the variety in individual organism size, age and sex. This study assessed the relationship between total mercury (Hg) concentrations in edible tissue, exoskeleton and viscera with length, weight and gender for 69 samples of crustaceans, Penaeus semisulcatus (n = 30), Thenus orientalis (n = 21) and Portunus pelagicus (n = 18) from the northern part of the Persian Gulf. Significant increase in the Hg level in muscle and viscera (r > 0.65, p < 0.01) with an increase in length and weight for all three species. No relationship was found between the Hg level in exoskeleton and length or weight. Significantly higher Hg levels (p < 0.01) were found in female P. semisulcatus than in males (muscle and viscera), but no gender differences were found for the other two species. PMID- 22057229 TI - Tissue concentrations of pesticides, PCBs and metals among ospreys, Pandion haliaetus, collected in France. AB - In this study, osprey (Pandion haliaetus) tissues collected in France were used for contaminants analyses by a non-invasive approach. 53 pesticides (organochlorine, organophosphate, carbamate, pyrethroids, herbicides, anticoagulant rodenticides), 13 PCBs, and 5 metals (mercury, lead, cadmium, copper and arsenic) were quantified in liver of 14 individual samples. PCBs and mercury were frequent (mean 0.5 mg/kg, range < d.l.-2.6 mg/kg and mean 3.4 mg/kg, range < d.l.-16.3 mg/kg wet weight, respectively). Inter-individual variations in contaminant diversity and amounts were noticed. Immediate conservation of the species in the country does not seem to be threatened by global contamination. PMID- 22057230 TI - Butyltin compounds in fish commonly sold in north of Iran. AB - Levels of tributyltin (TBT) and its degradation products, mono (MBT) and dibutyltin (DBT), were monitored in fish commonly consumed in Iran. Samples were purchased from fish markets at seasonal intervals in 2010 along the North coast of Iran. Concentration of MBT, DBT and TBT in the muscle of these fish were in the range of n.d. -1.01 +/- 0.84, n.d. -0.33 +/- 0.26 and n.d. -4.31 +/- 0.95 ngg(-1) (wet weight), respectively. Residue levels of butyltins were found lower than the tolerable average residue level of 100 ngg(-1) (wet weight). PMID- 22057231 TI - Determination of metal levels in thirteen fish species from Lakshadweep Sea. AB - A bio-monitoring study was performed to investigate the concentration of certain metals (cadmium, cobalt, copper, iron, magnesium, manganese, nickel, lead and zinc) in gill, skin and muscle of thirteen demersal fish species of Agatti Coast of Lakshadweep Sea. All the metal concentrations in gill are higher than skin and muscle. Concentrations of toxic metals such as Cd (0.61 +/- 0.67 MUg g(-1) in Gerres longirostris), Mn (0.83 +/- 1.21 MUg g(-1) in Lutjanus fulvus) and Ni (0.56 +/- 0.83 MUg g(-1) in L. bengalensis) were well above the permissible limits suggested by World Health Organization and Food and Agricultural Organizations. PMID- 22057232 TI - Association of clinical and genetical features in FMF with focus on MEFV strip assay sensitivity in 452 children from western Anatolia, Turkey. AB - The aim of this study was to determine the relationship between clinical findings and the most common mutated alleles of MEFV gene in a childhood population and to determine the sensitivity of the 12-mutation-strip assay test in familial Mediterranean fever (FMF). Records of 452 FMF children living in western Anatolia, Turkey, (12.3 +/- 4.7 years mean) were retrospectively reviewed. Of the 408 patients who met the Tel-Hashomer criteria, 364 were classified into two main groups (two-mutant/one-mutant allele) either of which had three subgroups. The two-mutant allele frequency was 51% and one-mutant allele 38%; 1% had complex mutant alleles and 10% no mutant-alleles. The mean severity score was 8.3 +/- 2.5. Most common clinical features were fever (81.9%), abdominal pain (86.3%) and myalgia (58.8%), and the least common ones: diarrhea (1.7%), protracted febrile myalgia (1.2%) and acute orchitis (1.5%). We detected 33 different genotypes of the MEFV gene: the most common mutant allele was M694V followed by symptomatic allele mutation of E148Q. Although not significantly associated with clinical findings, P369S mutation was not rare (7.5%). Phenotype-genotype correlation revealed that patients with two-allele mutations had more severe clinical presentation and high constipation rate (22.5%); 32.6% of patients with M694V/M694V had splenomegaly. Acute orchitis and protracted febrile myalgia as rare clinical findings were more common in M694V homozygotes. Comparisons of clinical findings among patients with one-mutation allele were made for the first time, but no significant association was found. Positive predictive value of strip assay screening for 12 mutations was recorded as 89%. We suggest that whole sequence analysis for supportive diagnosis of FMF should be performed for selected patients only. PMID- 22057233 TI - A novel automated indirect immunofluorescence autoantibody evaluation. AB - Autoantibodies (AAb), especially antinuclear (ANAs) and anticytoplasmatic antibodies (ACyA), are essential diagnosing markers for several autoimmune diseases. The current gold standard method for ANA detection is manual indirect immunofluorescence (IIF) on human epithelial-2 (HEp-2) cells. However, this technique is cost and time consuming, and characterized by considerable intra- and interlaboratory variability. Thus, an automated IIF-HEp-2 reader has been developed recently. In the current study, we compared the performance of the automated AAb IIF-HEp-2 interpretation to conventional detection methods. Autoantibody detection by IIF on HEp-2 cells was performed in a total of 260 sera of patients, including 34 with systemic lupus erythematosus, 111 with dermatomyositis or polymyositis, 74 with systemic sclerosis, 41 with rare AAb patterns, and 137 healthy individuals. Visual interpretation and routine immunoassays were compared with a novel automated IIF-HEp-2 system using Aklides pattern recognition algorithms. Positive AAbs were detected in 95-100% of rheumatic patients by automated interpretation, in 74-100% with manual reading, and in 64-100% by immunodot assay. Receiver operating characteristic curve analysis of fluorescent intensity revealed a high sensitivity and specificity for automated reading of AAb with an agreement ranging from 90% to 95% between manual and automated interpretation (kappa 0.554-0.69) for systemic sclerosis and myositis, respectively. This study demonstrates a good correlation between manual and automated interpretation of AAb including ANA and ACyA in patients with autoimmune diseases. Full automation of HEp-2 cell assay reading may minimize errors in ANA pattern interpretation and thus help in the standardization of ANA assessment. PMID- 22057234 TI - Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome. AB - Ollier disease and Maffucci syndrome are non-hereditary skeletal disorders characterized by multiple enchondromas (Ollier disease) combined with spindle cell hemangiomas (Maffucci syndrome). We report somatic heterozygous mutations in IDH1 (c.394C>T encoding an R132C substitution and c.395G>A encoding an R132H substitution) or IDH2 (c.516G>C encoding R172S) in 87% of enchondromas (benign cartilage tumors) and in 70% of spindle cell hemangiomas (benign vascular lesions). In total, 35 of 43 (81%) subjects with Ollier disease and 10 of 13 (77%) with Maffucci syndrome carried IDH1 (98%) or IDH2 (2%) mutations in their tumors. Fourteen of 16 subjects had identical mutations in separate lesions. Immunohistochemistry to detect mutant IDH1 R132H protein suggested intraneoplastic and somatic mosaicism. IDH1 mutations in cartilage tumors were associated with hypermethylation and downregulated expression of several genes. Mutations were also found in 40% of solitary central cartilaginous tumors and in four chondrosarcoma cell lines, which will enable functional studies to assess the role of IDH1 and IDH2 mutations in tumor formation. PMID- 22057235 TI - Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. AB - Using variants from the 1000 Genomes Project pilot European CEU dataset and data from additional resequencing studies, we densely genotyped 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease (cases) and 12,228 controls. We identified 13 new celiac disease risk loci reaching genome-wide significance, bringing the number of known loci (including the HLA locus) to 40. We found multiple independent association signals at over one-third of these loci, a finding that is attributable to a combination of common, low-frequency and rare genetic variants. Compared to previously available data such as those from HapMap3, our dense genotyping in a large sample collection provided a higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions. In particular, 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements. Altogether, we define the complex genetic architecture of the risk regions of and refine the risk signals for celiac disease, providing the next step toward uncovering the causal mechanisms of the disease. PMID- 22057236 TI - Ollier disease and Maffucci syndrome are caused by somatic mosaic mutations of IDH1 and IDH2. AB - Ollier disease and Maffucci syndrome are characterized by multiple central cartilaginous tumors that are accompanied by soft tissue hemangiomas in Maffucci syndrome. We show that in 37 of 40 individuals with these syndromes, at least one tumor has a mutation in isocitrate dehydrogenase 1 (IDH1) or in IDH2, 65% of which result in a R132C substitution in the protein. In 18 of 19 individuals with more than one tumor analyzed, all tumors from a given individual shared the same IDH1 mutation affecting Arg132. In 2 of 12 subjects, a low level of mutated DNA was identified in non-neoplastic tissue. The levels of the metabolite 2HG were measured in a series of central cartilaginous and vascular tumors, including samples from syndromic and nonsyndromic subjects, and these levels correlated strongly with the presence of IDH1 mutations. The findings are compatible with a model in which IDH1 or IDH2 mutations represent early post-zygotic occurrences in individuals with these syndromes. PMID- 22057237 TI - Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis. AB - The evolution of colorectal cancer suggests the involvement of many genes. To identify new drivers of intestinal cancer, we performed insertional mutagenesis using the Sleeping Beauty transposon system in mice carrying germline or somatic Apc mutations. By analyzing common insertion sites (CISs) isolated from 446 tumors, we identified many hundreds of candidate cancer drivers. Comparison to human data sets suggested that 234 CIS-targeted genes are also dysregulated in human colorectal cancers. In addition, we found 183 CIS-containing genes that are candidate Wnt targets and showed that 20 CISs-containing genes are newly discovered modifiers of canonical Wnt signaling. We also identified mutations associated with a subset of tumors containing an expanded number of Paneth cells, a hallmark of deregulated Wnt signaling, and genes associated with more severe dysplasia included those encoding members of the FGF signaling cascade. Some 70 genes had co-occurrence of CIS pairs, clustering into 38 sub-networks that may regulate tumor development. PMID- 22057238 TI - The trans-sutural distraction osteogenesis for 22 cases of craniosynostosis: a new, easy, safe, and efficient method in craniosynostosis surgery. AB - BACKGROUND: Distraction osteogenesis for the treatment of craniosynostosis is becoming more widely used as it is simple, there are less transfusions, and a decreased incidence of complications, although a secondary procedure for the removal of the distractors is necessary. However, to date all previous procedures have still been complicated. The authors present a novel trans-sutural distraction osteogenesis method (TSuDO) for the treatment of all types of craniosynostosis. METHODS: The TSuDO consisted of simple suturectomy of the pathologic suture followed by direct distraction of the suturectomy site only. Types of TSuDO conducted were sagittal TSuDO in 6 patients, coronal TSuDO in 5 patients, unilateral coronal TSuDO in 8 patients, lambdoid TSuDO in 2 patients, and metopic TSuDO in 1 patient (total = 22). Mean age was 9.3 +/- 12.7 months. RESULTS: The mean operation time was 143.6 +/- 50.2 min, and mean total transfusion volume of blood components was 131.1 +/- 78.3 ml. Immediate correction of the abnormal head contour after distraction was observed in all patients, and no complications were encountered except for 1 patient whose distractor malfunctioned and 2 who showed prolonged discharges from the pin sites (controlled by antibiotics). CONCLUSION: TSuDO is a simple, effective, and safe method for the treatment of all types of craniosynostosis, and is especially effective for the correction of unilateral coronal craniosynostosis. PMID- 22057239 TI - Low densities of serotonin and peptide YY cells in the colon of patients with irritable bowel syndrome. AB - BACKGROUND: The gut hormones are important in regulating gastrointestinal motility. Disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). Reduced endocrine cell density, as revealed by chromogranin A, has been reported in the colon of IBS patients. AIMS: To investigate a possible abnormality in the colonic endocrine cells of IBS patients. METHODS: A total of 41 patients with IBS according to Rome Criteria III and 20 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. The biopsies were immunostained for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), entroglucagon, and somatostatin cells. Cell densities were quantified by computerized image analysis. RESULTS: Serotonin and PYY cell densities were reduced in the colon of IBS patients. PP, entroglucagon, and somatostatin-immunoreactive cells were too few to enable reliable quantification. CONCLUSION: The cause of these observations could be primary genetic defect(s), secondary to altered serotonin and/or PYY signaling systems and/or subclinical inflammation. Serotonin activates the submucosal sensory branch of the enteric nervous system and controls gastrointestinal motility and chloride secretion via interneurons and motor neurons. PYY stimulates absorption of water and electrolytes, and inhibits prostaglandin (PG) E2, and vasoactive intestinal peptide, which stimulates intestinal fluid secretion and is a major regulator of the "ileal brake". Although the cause and effect relationship of these findings is difficult to elucidate, the abnormalities reported here might contribute to the symptoms associated with IBS. PMID- 22057240 TI - Levels of evidence in endoscopic ultrasonography: a systematic review. AB - BACKGROUND AND AIMS: A prolific trend currently designates endoscopic ultrasonography (EUS) literature. We aimed to record all EUS-studies published during the past decade and evaluate them in terms of scientific quality, creating a stratification based on levels of evidence (LE). METHODS: All articles on EUS published between January 2001 and December 2010 were retrieved using a Pubmed and Cochrane Library search. Inclusion criteria were: original research papers (randomized controlled trials-RCTs, prospective and retrospective studies), meta analyses, reviews and surveys pertinent to gastrointestinal EUS. Levels of evidence (LE) were assessed using the North of England evidence-based guidelines. RESULTS: Overall, 1,832 eligible articles were reviewed. The majority (46.1%) of reports comprised retrospective descriptive studies (LE III). Expert reviews and committee reports (LE IV) accounted for 28.9%, well-designed quasi-experimental studies (LE IIb) for 20.1%, RCTs (LE Ib) for 2.4%, prospective controlled trials (LE IIa) for 1.4%, and meta-analyses (LE Ia) for 1.1% of the total. High LE (Ia Ib) were assigned to loco-regional staging of luminal gastrointestinal cancers; mediastinal staging of lung cancer; diagnostic work-up of solid pancreatic tumors, suspected biliary obstruction and choledocholithiasis; celiac plexus neurolysis; and pancreatic pseudocysts drainage. Intermediate to low LE (IIa-IV) were assigned to submucosal tumors, pancreatic cysts, chronic pancreatitis and novel therapeutic applications (pancreato-biliary drainage, tumor ablation). CONCLUSIONS: Diagnostic and staging EUS has matured and has proven its clinical impact on patient management. Therapeutic or interventional EUS is still evolving and more quality research and data are needed to establish EUS as the best next intervention to perform once firm evidence is available. PMID- 22057241 TI - On the association between soft drink consumption and Helicobacter pylori infection. AB - BACKGROUND: The association between soft drink (SD) consumption and Helicobacter pylori infection remains unclear. AIM: To examine the relationship between SD consumption and H. pylori infection. METHODS: A prospective study included individuals who were referred for an upper gastrointestinal endoscopic examination because chronic dyspepsia within a period of 1 year. In addition to determining daily SD consumption and the risk factors for H. pylori infection by asking all study participants to complete a standard questionnaire about their diet, daily eating and drinking habits, and their lifestyle before undergoing the endoscopic examination. H. pylori infection was established by a positive result of the rapid urease test and histology. RESULTS: Of the 312 individuals who were referred for the endoscopic examination because chronic dyspepsia, 269 met the inclusion criteria. H. pylori infection was found in 164 (61%) of the 269 study participants, and, of these, 104/164 individuals were SD consumers with H. pylori infection versus 24/105 individuals without H. pylori infection (63 vs. 23%, respectively, P < 0.001). The results of the multiple logistic regression analysis showed that SD consumption (odds ratio = 4.0; 95 % confidence interval = 3.19-5.82,P < 0.001), was associated with H. pylori infection. CONCLUSION: SD consumption is associated with H. pylori infection in individuals with chronic dyspepsia. PMID- 22057242 TI - Age- and chamber-specific differences in oxidative stress after ischemic injury. AB - Each year, tens of thousands of children undergo cardiopulmonary bypass (CPB) to correct congenital heart defects. Although necessary for surgery, CPB involves stopping the heart and exposing it to ischemic conditions. On reoxygenation, the heart can experience effects similar to that of acute myocardial infarction. Although much is known about adult injury, little is known about the effects of global ischemia on newborn ventricles. We studied newborn (2 to 4 days old) and adult (>8 weeks old) rabbit hearts subjected to ischemia-reperfusion (30 min of ischemia and 60 min of reperfusion). Our data demonstrated chamber- and age specific changes in oxidative stress. During ischemia, hydrogen peroxide (H(2)O(2)) increased in both right-ventricular (RV) and left-ventricular (LV) myocytes of the newborn, although only the RV change was significant. In contrast, there was no significant increase in H(2)O(2) in either RV or LV myocytes of adults. There was a fivefold increase in H(2)O(2) formation in newborn RV myocytes compared with adults (P = 0.006). In whole-heart tissue, superoxide dismutase activity increased from sham versus ischemia in the left ventricle of both adult and newborn hearts, but it was increased only in the right ventricle of the newborn heart. Catalase activity was significantly increased after ischemia in both adult ventricles, whereas no increase was seen in newborn compared with sham hearts. In addition, catalase levels in newborns were significantly lower, indicating less scavenging potential. Nanoparticle encapsulated ebselen, given as an intracardiac injection into the right or left ventricle of newborn hearts, significantly increased functional recovery of developed pressure only in the right ventricle, indicating the potential for localized antioxidant therapy during and after pediatric surgical procedures. PMID- 22057243 TI - Improvement and defervescence of persistent fever after one course of intravenous immunoglobulin in a patient with bacterial infective endocarditis. PMID- 22057244 TI - Environmental factors and rheumatic heart disease in Fiji. AB - Rheumatic heart disease (RHD) is an important cause of cardiac morbidity and mortality globally, particularly in the Pacific region. Susceptibility to RHD is thought to be due to genetic factors that are influenced by environmental factors, such as crowding and poverty. However, there are few data relating to these environmental factors in the Pacific region. We conducted a case-control study of 80 cases of RHD with age- and sex-matched controls in Fiji using a questionnaire to investigate associations of RHD with a number of environmental factors. There was a trend toward increased risk of RHD in association with poor quality housing and lower socioeconomic status, but only one factor, maternal unemployment, reached statistical significance (OR 2.6, 95% confidence interval 1.2-5.8). Regarding crowding, little difference was observed between the two groups. Although our data do not allow firm conclusions, they do suggest that further studies of socioeconomic factors and RHD in the Pacific are warranted. They also suggest that genetic studies would provide an insight into susceptibility to RHD in this population. PMID- 22057245 TI - Impact of central hypovolemia on photoplethysmographic waveform parameters in healthy volunteers part 2: frequency domain analysis. AB - OBJECTIVE: The photoplethysmographic (PPG) waveforms are modulated by the respiratory, cardiac and autonomic nervous system. Lower body negative pressure (LBNP) has been used as an experimental tool to simulate loss of central blood volume in humans. The aim of our research is to understanding PPG waveform changes during progressive hypovolemia. METHODS: With IRB approval, 11 volunteers underwent a LBNP protocol at baseline, 30, 75, and 90 mmHg (or until the subject became symptomatic). Subjects were monitored with finger and ear pulse oximeter probes, ECG, and finger arterial blood pressure monitor (FABP). Heart rate variability (HRV) was analyzed to high frequency (HRV-HF) (0.12-0.4 Hz) and low frequency (HRV-LF) (0.04-0.12 Hz). Frequency analysis of PPG waveforms were computed to low (0.04-0.11 Hz) frequency (PPG-LF), intermediate (0.12-0.18 Hz) frequency (PPG-IF), respiratory (0.19-0.3 Hz) frequency (PPG-Resp.) and cardiac (0.75-2.5 Hz) frequency (PPG-Cardiac)during different phases of LBNP protocol RESULTS: Heart rate increased significantly while systolic, mean and pulse pressure of the FABP declined slowly together with significant reductions in HRV HF (0.12-0.4 Hz) and HRV-LF (0.04-0.12 Hz) power at LBNP(75). There was significant reduction in finger PPG-Cardiac modulation which is consistent with the reduction in the pulse pressure of the FABP. As the LBNP progress there was shift in the amplitude density of the ear PPG-Cardiac to PPG-Resp. Oscillation as an evidence of progressive hypovolemia with reduction in pulse pressure and increase in the respiratory induced variations. At LBNP(75), there were significant increased (>140% increase from the baseline) in ear PPG-IF (0.12-0.18 Hz) in the meantime HRV-HF showed significant reduction (>89%) from the baseline. At the symptomatic phase; there was a shift in ear PPG-IF to PPG-Resp. With an increase in the ear PPG-Resp. Modulation to >=175% from the baseline CONCLUSION: The pulse oximeter waveform contains a complex mixture of the effect of cardiac, venous, autonomic, and respiratory systems on the central and peripheral circulation. The occurrence of autonomic modulation needs to be taken into account when studying signals that have their origins from central sites (e.g. ear and forehead). PMID- 22057246 TI - Evaluation of a CO2 partial rebreathing functional residual capacity measurement method for use during mechanical ventilation. AB - OBJECTIVE: There is a need for an automated bedside functional residual capacity (FRC) measurement method that does not require a step change in inspired oxygen fraction. Such a method can be used for patients who require a high inspired oxygen fraction to maintain arterial oxygenation and for patients ventilated using a circle breathing system commonly found in operating rooms, which is not capable of step changes in oxygen. We developed a CO(2) rebreathing method for FRC measurement that is based on the change in partial pressure of end-tidal carbon dioxide and volume of CO(2) eliminated at the end of a partial rebreathing period. This study was designed to assess the accuracy and precision of the proposed FRC measurement system compared to body plethysmography and nitrogen washout FRC. METHODS: Accuracy and precision of measurements were assessed by comparing the CO(2) rebreathing FRC values to the gold standard, body plethysmography FRC, in twenty spontaneously breathing volunteers. The CO(2) rebreathing FRC measurements were then compared to nitrogen washout FRC in twenty intensive care patients whose lungs were mechanically ventilated. For each subject, an average value of CO(2) rebreathing FRC was compared to the average gold standard method. Measurements were accepted for statistical analysis if they had been recorded from periods of stable tidal ventilation, defined as a coefficient of variation of tidal volume of <0.13. RESULTS: Compared to body plethysmography, the accuracy (average error) for the CO(2) rebreathing method during stable ventilation (n = 8) was 0.03 L and precision (1 standard deviation of the error) was 0.29 L (0.8 +/- 7.6% of body plethysmography). During stable mechanical ventilation (n = 9), the accuracy was -0.02 L and precision was 0.26 L (-1.1 +/- 12.6% of nitrogen washout). CONCLUSIONS: The CO(2) rebreathing method for FRC measurement provides acceptable accuracy and precision during stable ventilation compared to the gold standards of body plethysmography and nitrogen washout. The results based on periods of stable ventilation best approximate the performance of the system in the likely areas of application during controlled mechanical ventilation. Further study of the CO(2) rebreathing method is needed to evaluate accuracy in a larger group of controlled mechanical ventilation patients, including patients with respiratory insufficiency and significant lung injury. PMID- 22057247 TI - The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia. AB - OBJECTIVE: Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and grey matter metabolites in a slab cranial to the ventricles and relate these to the outcome. METHODS: A standard 2D-chemical shift imaging protocol was used for measuring a transverse volume of interest located cranial to the ventricles allowing for direct comparison of the metabolites in white and grey matter brain tissue in 24 term asphyxiated newborns aged 3 to 16 days. RESULTS: Cho, NAA and Lact showed significant differences between four subgroups of asphyxiated infants with more and less favourable outcomes. High levels of Cho and Lact in the grey matter differentiated non-survivors from survivors (P = 0.003 and P = 0.017, respectively). CONCLUSION: In perinatal asphyxia the levels of Cho, NAA and Lact in both white and grey matter brain tissue are affected. The levels of Cho and Lact measured in the grey matter are the most indicative of survival. It is therefore advised to include grey matter brain tissue in the region of interest examined by multivoxel MR spectroscopy. KEY POINTS: Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia. Choline and lactate levels in grey matter seem the best indicators of survival. Both grey and white matter should be examined during spectroscopy for perinatal asphyxia. PMID- 22057248 TI - Hypervascular hepatocellular carcinomas: detection with gadoxetate disodium enhanced MR imaging and multiphasic multidetector CT. AB - OBJECTIVES: To retrospectively compare the accuracy of detection of hypervascular hepatocellular carcinoma (HCC) by multiphasic multidetector CT and by gadoxetate disodium-enhanced MR imaging. METHODS: After ethical approval, we analysed a total of 73 hypervascular HCC lesions from 31 patients suspected of having HCC, who underwent both gadoxetate disodium-enhanced MR imaging and multiphasic multidetector CT. Five blinded observers independently reviewed CT images, as well as dynamic MR images alone and combined with hepatobiliary phase MR images. Diagnostic accuracy (Az values), sensitivities and positive predictive values were compared by using the Scheffe post hoc test. RESULTS: The mean Az value for dynamic and hepatobiliary phase MR combined (0.81) or dynamic MR images alone (0.78) was significantly higher than that for CT images (0.67, P < 0.001, 0.005, respectively). The mean sensitivity of the combined MR images (0.67) was significantly higher than that of dynamic MR alone (0.52, P < 0.05) or CT images (0.44, P < 0.05). The mean positive predictive values were 0.96, 0.95 and 0.94, for CT, dynamic MR alone and combined MR images, respectively. CONCLUSIONS: Compared with multiphasic multidetector CT, gadoxetate disodium-enhanced MR imaging combining dynamic and hepatobiliary phase images results in significantly improved sensitivity and diagnostic accuracy for detection of hypervascular HCC. KEY POINTS: Gadoxetate disodium is a new liver-specific MR imaging contrast agent. Gadoxetate disodium-enhanced MRI helps the assessment of patients with liver disease. It showed high diagnostic accuracy for the detection of hepatocellular carcinoma. PMID- 22057250 TI - PFOS elicits transcriptional responses of the ER, AHR and PPAR pathways in Oryzias melastigma in a stage-specific manner. AB - Perfluorooctane sulfonate (PFOS) is widely distributed in seawater. However, the effects of PFOS on important receptors involved in the toxicity of POPs have not been fully defined, especially for the embryonic stages of marine fish. In this study, we examined the transcriptional responses and PFOS accumulation in the marine medaka embryos at the early and late developmental stages of 4 and 10 dpf upon PFOS exposure (1, 4, and 16mg/L). PFOS accumulated in the embryos, and the embryonic burdens of PFOS at 10 dpf were markedly higher than those at 4 dpf. Moreover, thirteen genes involved in three important POPs-related receptor pathways, including ER, AHR and PPAR, were cloned and investigated. The mRNA expression levels of ERalpha and ERgamma were not significantly altered, but the estrogenic marker genes were downregulated upon PFOS exposure at 4 dpf. Conversely, ERs and related marker genes all were significantly upregulated at 10 dpf. The expressions of ARNT and cyp1a were both upregulated at 4 dpf, while no obvious changes were detected at 10 dpf. The expressions of cyp19a and cyp19b were regulated by PFOS in a stage-specific manner. PFOS produced different effects on three isoforms of PPAR. PPARalpha and PPARbeta were first inhibited at 4 dpf and were induced at 10 dpf. PFOS did not elicit a change in PPARgamma expression at either stage. In conclusion, this study showed that PFOS has an estrogenic activity and endocrine-disruptive properties. Meanwhile, PFOS could elicit transcriptional responses on POPs-related pathways in a stage-specific manner. PMID- 22057251 TI - Imposex development in Nucella lapillus--evidence for the involvement of retinoid X receptor and androgen signalling pathways in vivo. AB - Imposex in female gastropods is a widely documented masculinisation phenomenon in response to tributyltin (TBT) exposure. Although it is generally accepted that imposex is a case of endocrine disruption the underlying mechanisms are controversially discussed with aromatase inhibition and retinoid X receptor (RXR) signalling pathways as two conflicting hypotheses. Hence, we performed injection experiments with the marine dogwhelk Nucella lapillus. As expected TBT induced imposex in all test specimens while the natural RXR ligand 9 cis-retinoic acid did not cause significant effects. Additionally, TBT effects were suppressed if the organotin compound was simultaneously injected with an androgen receptor inhibitor (cyproterone acetate) but not if co-administered with the synthetic RXR antagonist HX531. In contrast, the injection of the RXR agonist HX630 resulted in imposex development in nearly 100% females. Therefore, the results provide evidence for the involvement of the RXR and the androgen signalling pathway. Further investigations are necessary to resolve the biochemical mechanism of imposex development. PMID- 22057252 TI - Competition increases toxicant sensitivity and delays the recovery of two interacting populations. AB - We investigated how persistent competitive pressure alters toxicant sensitivity and recovery from a pesticide pulse at community level. Interacting populations of Daphnia (Daphnia magna) and Culex larvae (Culex pipiens molestus) were pulse exposed (48 h) to the pyrethroid fenvalerate. The abundance and biomass of the populations were monitored by non-invasive image analysis. Shortly after exposure, Daphnia showed a concentration-response relationship with the toxicant with an LC50 of 0.9 MUg/L. Culex larvae were slightly less sensitive with an LC50 of 1.7 MUg/L. For both species, toxicant sensitivity increased with the population biomass of the respective species before exposure, which is explained by intraspecific competition. Several weeks after exposure to the highest treatment concentration of 1 MUg/L, the slight differences in sensitivity between the two species were amplified to contrasting long-term effects due to interspecific competition: high interspecific competition impaired the recovery of Daphnia. Subsequently, Culex larvae profited from the slow recovery of Daphnia and showed an increased success of emergence. We conclude that, in natural systems where competition is present, such competitive processes might prolong the recovery of the community structure. Hence, natural communities might be disturbed for a longer period by toxic exposure than predicted from single species tests alone. PMID- 22057253 TI - Adaptation of copper community tolerance levels after biofilm transplantation in an urban river. AB - The Water Framework Directive requires the development of biological tools which can act as early-warning indicators of a sudden increase (accidental pollution) or decrease (recovery due to prevention) of the chemical status of aquatic systems. River biofilms, which respond quickly to modifications of environmental parameters and also play a key part in the functioning of aquatic ecosystems, are therefore good candidates to monitor an increase or a decrease of water pollution. In the present study, we investigated the biological response of biofilms transplanted either upstream (recovery) or downstream (deterioration of exposure levels) the urban area of Paris (France). Both modifications of Cu community tolerance levels and of global bacterial and eukaryotic community structure using automated ribosomal intergenic spacer analysis (ARISA) fingerprints were examined 15 and 30 days after the transplantation. Cu tolerance levels of the heterotrophic component of biofilms were assessed using a short term toxicity test based on beta-glucosidase (heterotrophic) activity. Cu tolerance increased for biofilms transplanted upstream to downstream Paris (5 fold increase on day 30) and conversely decreased for biofilms transplanted downstream to upstream (8-fold decrease on day 30). ARISA fingerprints revealed that bacterial and eukaryotic community structures of transplanted biofilms were closer to the structures of biofilms from the transplantation sites (or sites with similar contamination levels) than to biofilms from their sites of origin. Statistical analysis of the data confirmed that the key factor explaining biofilm Cu tolerance levels is the sampling site and not the site of origin. It also showed that Cu tolerance levels are related to the global urban contamination (both metals and nutrients). The study shows that biofilms adapt fast to modifications of their surroundings. In particular, community tolerance varies quickly and reflects the new exposure levels only 15 days after transplantation. Those results support the use of biofilms as reliable early-warning indicators of diffuse urban contamination. PMID- 22057254 TI - Biotransformation modulation and genotoxicity in white seabream upon exposure to paralytic shellfish toxins produced by Gymnodinium catenatum. AB - Fish are recurrently exposed to paralytic shellfish toxins (PSTs) produced by Gymnodinium catenatum. Nevertheless, the knowledge regarding metabolism of PSTs and their toxic effects in fish is scarce. Consequently, the current study aims to investigate the role of phase I and II detoxification enzymes on PST metabolism in the liver of white seabream (Diplodus sargus), assessing ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) activities. Moreover, the genotoxic potential of PSTs was examined through the erythrocytic nuclear abnormality (ENA) assay. Fish were intracoelomically (IC) injected with a nominal dose (expressed as saxitoxin equivalents) of 1.60 MUg STXeq kg-1 semipurified from a G. catenatum cell culture with previously determined toxin profile. Fish were sacrificed 2 and 6 days after IC injection. PST levels determined in fish liver were 15.2 and 12.2 MUg STXeq kg-1, respectively, at 2 and 6 days after the injection. Though several PSTs were administered, only dcSTX was detected in the liver after 2 and 6 days. This was regarded as an evidence that most of the N-sulfocarbamoyl and decarbamoyl toxins were rapidly biotransformed in D. sargus liver and/or eliminated. This was corroborated by a hepatic GST activity induction at 2 days after injection. Hepatic EROD activity was unresponsive to PSTs, suggesting that these toxins enter phase II of biotransformation directly. The genotoxic potential of PSTs was also demonstrated; these toxins were able to induce cytogenetic damage, such as chromosome (or chromatid) breaks or loss and segregational anomalies, measured by the ENA assay. Overall, this study pointed out the ecological risk associated with the contamination of fish with PSTs generated by G. catenatum blooms, providing the necessary first data for a proper interpretation of biomonitoring programs aiming to assess the impact of phytoplankton blooms in fish. PMID- 22057255 TI - Venlafaxine and atenolol disrupt epinephrine-stimulated glucose production in rainbow trout hepatocytes. AB - The beta-blocker atenolol (ATEN), and the selective serotonin and norepinephrine reuptake inhibitor, venlafaxine (VEN) are found in municipal wastewater effluents, but little is known about the effect of these pharmaceuticals on aquatic animals. We tested the hypothesis that VEN and ATEN disrupt acute stress mediated glucose production in fish liver. To this end, rainbow trout (Oncorhynchus mykiss) hepatocytes were exposed in vitro to different concentrations (0, 0.1, 10, 1000 nM) of VEN or ATEN and glucose production in response to either cortisol or epinephrine (two key stress hormones) was ascertained. Both VEN and ATEN did not affect either the unstimulated or cortisol (100 ng/mL)-stimulated glucose release over a 24 h period. The acute (3 h) unstimulated glucose production by isolated hepatocytes in suspension was also not modified by ATEN, while VEN (100 and 1000 nM) reduced basal glucose release. However, ATEN, even at concentration as low as 0.01 nM completely abolished epinephrine (1 MUM)-induced glucose production in trout hepatocytes. Interestingly, VEN also suppressed epinephrine-induced glucose production but only at higher concentrations (100 and 1000 nM). Neither VEN nor ATEN significantly impacted the glucose production in response to either 8-bromo-cAMP (cAMP analogue) or glucagon (a metabolic hormone that increases glucose production) stimulation. ATEN but not VEN attenuated the epinephrine-induced increase in glucose transporter 2 (GLUT2) mRNA abundance in trout hepatocytes. Taken together, our results suggest that the impact of ATEN and VEN on glucose production involves inhibition of beta-adrenoceptor signaling in trout hepatocytes. Overall, VEN and ATEN are beta-blockers and may disrupt the adaptive acute glucose response to a secondary stressor in rainbow trout. PMID- 22057257 TI - An activated immune and inflammatory response targets the pancreas of newborn pigs with cystic fibrosis. AB - BACKGROUND/AIMS: In cystic fibrosis (CF), pancreatic disease begins in utero and progresses over time to complete destruction of the organ. Although inflammatory cells have been detected in the pancreas of humans and pigs with CF, their subtypes have not been characterized. METHODS: Using four-color flow cytometry, we analyzed the surface antigens of leukocytes in pancreas, blood, and mesenteric lymph nodes (MLN) of newborn pigs with CF (CFTR(-/-) and CFTR(Delta)(F508/)(Delta)(F508)) and in those without CF (CFTR(+/-), CFTR(+/)(Delta)(F508), CFTR(+/+)). Pancreatic histopathology was examined with HE stain. RESULTS: CF pig pancreas had patchy distribution of inflammatory cells with neutrophils/macrophages in dilated acini, and lymphocytes in the interstitium compared to non-CF. B cells, effector (MHC-II(+)) and cytotoxic (CD2(+)CD8(+)) gammadelta T cells, activated (MHC-II(+) and/or CD25(+)) and effector (CD4(+)CD8(+)) alphabeta T helper cells, effector natural killer cells (MHC-II(+)CD3(-)CD8(+)), and monocytes/macrophages and neutrophils were increased in the CF pig pancreas compared to pigs without CF. Blood and MLN leukocyte populations were not different between CF and non-CF pigs. CONCLUSIONS: We discovered an activated immune response that was specific to the pancreas of newborn CF pigs; inflammation was not systemic. The presence of both innate and adaptive immune cells suggests that the disease process is complex and extensive. PMID- 22057258 TI - [Desmopressin parenteral in patients with VWD1, VWD 2A and thrombocytopathy]. AB - Desmopressin (DDAVP, Minirin(r) parenteral), which induces the release of von Willebrand factor from endogenous stores, is indicated in von Willebrand disease type 1 (VWD 1). In the present study effectiveness of DDAVP was tested and side effects were recorded in patients with VWD 1, von Willebrand disease type 2 (VWD 2) or thrombocytopathy (TCP). PATIENTS, METHODS: Subjects were analysed prior to and after Minirin parenteral infusion (0.4 MUg/kg body weight (b.w.) over 60 minutes) for partial thromboplastin time (PTT, seconds), ADP/epinephrine triggered platelet-function analyzer (PFA-100) occlusion time (seconds), factor VIII activity (FVIII, %), VWF as ristocetin cofactor activity (VWF:RCo, %) and VWF antigen (VWF:Ag, %). Side effects of DDAVP during operative interventions were recorded per questionnaires by the patients. RESULTS: The mean +/- standard deviation dose (n = 165 patients) of Minirin parenteral administered was 0.37 +/- 0.02 MUg/kg b.w., most often upcoming dental operations (57%) necessitated testing. Coagulation parameters of patients with VWD 1 or TCP normalised in almost all patients, but only in approximately 50% of patients with VWD 2 respectively. Appraisal of effectiveness of Minirin parenteral as good was 96% in case of VWD 1 and 95 % in case of TCP. During minor surgeries (n = 23) in 91% of the patients no complications and in 2 patients (9%) postoperative haemorrhages without need for further interventions occurred, but 83% of the patients reported adverse reactions in the questionnaires, although Minirin parenteral was well tolerated by all patients during DDAVP efficacy tests. CONCLUSION: Desmopressin is well tolerated and affective in patients with VWD 1 and thrombocytopathy. PMID- 22057259 TI - A carbon nanoparticle-based low-background biosensing platform for sensitive and label-free fluorescent assay of DNA methylation. AB - Combining a DNA intercalator, SYBR Green I, and enzyme-linkage reactions with carbon nanoparticles, a low-background biosensing platform for label-free and sensitive fluorescent assay of DNA methylation is reported. PMID- 22057260 TI - Influenza-related excess mortality necessitates an urgent call for action. PMID- 22057261 TI - Gastric wash-based molecular testing for antibiotic resistance in Helicobacter pylori. AB - BACKGROUND: A number of noninvasive tests have been developed to establish the presence of Helicobacter pylori infection. However, thus far these tests have only been capable of detecting its presence. An increasing number of antibiotic resistant H. pylori infections have been reported and they are known to be correlated with 23S rRNA single nucleotide polymorphisms (SNPs). We hypothesized that genomic analysis of H. pylori recovered from gastric washes could not only be less invasive, but also useful as a screening test and for assessing the outcome of eradication therapy. METHODS: Biopsy specimens and gastric washes were collected from 100 patients during endoscopic examination. Then we analyzed 23S rRNA, ureA, and cagA genes using PCR and high-throughput pyrosequencing analysis. RESULTS: Forty-five percent (44/97) of patients tested positive for ureA and 42.3% (41/97) tested positive by a rapid urease test. One hundred percent (35/35) of patients who tested positive by both methods were observed to have the cagA gene. Among these 35 patients, 23S rRNA SNPs were present in 34.3% (12/35). CONCLUSIONS: Gastric wash-based PCR and a pyrosequencing assay were used to rapidly detect and estimate the number of 23S rRNA SNPs in clinical isolates of H. pylori. Not only is this a less invasive technique, but it can also diagnose drug resistance. PMID- 22057262 TI - Development of sensitive single-round pol or env RT-PCR assays to screen for XMRV in multiple sample types. AB - The potential association between xenotropic murine leukemia virus-related virus (XMRV) and prostate cancer and chronic fatigue syndrome (CFS) has been much debated. To help resolve the potential role of XMRV in human disease, it is critical to develop sensitive and accurate reverse transcriptase (RT)-PCR assays to screen for the virus. Single-round RT-PCR assays were developed on the automated m2000TM system for detection of the pol or env regions of XMRV in whole blood, plasma, urine cell pellets and urogenital swab samples. Assay performance was assessed by testing two blinded panels, one comprised of whole blood and the other of plasma spiked with serial dilutions of XMRV-infected tissue culture cells and supernatant, respectively, prepared by the Blood XMRV Scientific Research Working Group (SRWG). For both whole blood and plasma panel testing, the assays showed excellent specificity and sensitivity as compared to the other tests included in the SRWG phase I study. Analytical specificity of the assays was also evaluated. Neither pol nor env PCR assays detected a panel of potential cross-reactive microorganisms, although some cross-reaction was observed with mouse genomic DNA. Screening of 196 normal human blood donor plasma, 214 HIV-1 seropositive plasma, 20 formalin-fixed paraffin-embedded (FFPE) prostate cancer specimens, 4 FFPE benign prostate specimens, 400 urine pellets from prostate cancer patients, 166 urine pellets from non-prostate cancer patients, and 135 cervical swab specimens, detected no samples as unequivocally XMRV positive. PMID- 22057263 TI - A retrospective review of 15 patients with familial myasthenia gravis over a period of 25 years. AB - We observed, during a 25-year period, 15 patients from 6 families with autoimmune myasthenia gravis (all Chinese Han from Guangdong Province) referred to our department. Their mean onset age was 13.4 years (range 2-25 years) with 10 patients with juvenile onset. The female:male ratio was 3:2. Acetylcholine receptors antibody titers were increased in 11 patients (range 1.62-19.8 nmol/L). Thymectomy was performed in six patients, who received corticosteroids /immune inhibitor plus pyridostigmine treatments after surgery. The other patients were placed on therapy with azathioprine, cyclophosphamide, corticosteroids and acetylcholinesterase inhibitors. All patients responded well to immunosuppressants, and psychiatric symptoms were observed only in one patient who received a high dose of corticosteroids. Patients with generalized type in the same family had different presentations with variable prognosis. HLA-A 0207 was found in 9 patients (9/15), HLA-B 4601 in 11 patients (11/15), and HLA-DRB1 0901 in 12 patients (12/15). When compared to familial autoimmune myasthenia gravis in other countries, we observed peculiar characteristics of Chinese populations, such as the within-family consistency was only found in families with ocular MG type (50% of all MG families), while the pathogenetic conditions and the prognoses of the generalized MG patients may differ greatly within the same family. These findings may shed new light on the genetic predisposition and the origin of immune abnormalities of MG patients. PMID- 22057264 TI - Position paper of the Italian Society for the study of Dementias (SINDEM) on the proposal of a new lexicon on Alzheimer disease. AB - A panel of Italian neurologists of the Italian Society for the study of Dementias (SINDEM) discussed the recently proposed new lexicon for Alzheimer disease (AD) and the related diagnostic criteria for the different phases of the disease (Preclinical AD, prodromal AD and Alzheimer's dementia) (Dubois et al. in Lancet Neurol 6:734-746, 2007; in Lancet Neurol 9:1118-1127, 2010). The aim of this discussion was to reach a consensus, among the Italian neurologists involved in the study and care of persons with dementia, in particular in reference to the potential use of the proposed diagnostic criteria in clinical practice. After having critically revised the scientific evidence related to the new lexicon and to the new proposed diagnostic criteria, the panel concluded that the proposed new diagnostic criteria and the new proposed lexicon for AD are conceptually attractive. However, the evidence about the instrumental and laboratory markers for the diagnosis of the preclinical and asymptomatic states of the disease are, until to now, insufficient to support the routine clinical use of these investigations. PMID- 22057265 TI - Fatal encephalitis associated with novel influenza A (H1N1) virus infection in a child. AB - A 4-year-old girl presented with fever, coughing, and vomiting; followed by unconsciousness. Magnetic resonance imaging showed hyperintense changes in the thalami bilaterally, brain stem, cerebellum, and subcortical cortex. Novel influenza A (H1N1) virus was identified by polymerase chain reaction in patient's nasopharyngeal swab specimen. We reported a rare case of clinically severe, novel influenza A-associated encephalitis. Novel influenza A should be considered in the differential diagnosis in patients with seizures and mental status changes, especially during an influenza outbreak. PMID- 22057266 TI - Anterior semicircular canal BPPV with positional downbeat nystagmus without latency, habituation and adaptation. PMID- 22057267 TI - Tumor cell metabolism: an integral view. AB - Cancer is a genetic disease that is caused by mutations in oncogenes, tumor suppressor genes and stability genes. The fact that the metabolism of tumor cells is altered has been known for many years. However, the mechanisms and consequences of metabolic reprogramming have just begun to be understood. In this review, an integral view of tumor cell metabolism is presented, showing how metabolic pathways are reprogrammed to satisfy tumor cell proliferation and survival requirements. In tumor cells, glycolysis is strongly enhanced to fulfill the high ATP demands of these cells; glucose carbons are the main building blocks in fatty acid and nucleotide biosynthesis. Glutaminolysis is also increased to satisfy NADPH regeneration, whereas glutamine carbons replenish the Krebs cycle, which produces metabolites that are constantly used for macromolecular biosynthesis. A characteristic feature of the tumor microenvironment is acidosis, which results from the local increase in lactic acid production by tumor cells. This phenomenon is attributed to the carbons from glutamine and glucose, which are also used for lactic acid production. Lactic acidosis also directs the metabolic reprogramming of tumor cells and serves as an additional selective pressure. Finally, we also discuss the role of mitochondria in supporting tumor cell metabolism. PMID- 22057268 TI - Identification of gene encoding Plasmodium knowlesi phosphatidylserine decarboxylase by genetic complementation in yeast and characterization of in vitro maturation of encoded enzyme. AB - The 23-megabase genome of Plasmodium falciparum, the causative agent of severe human malaria, contains ~5300 genes, most of unknown function or lacking homologs in other organisms. Identification of these gene functions will help in the discovery of novel targets for the development of antimalarial drugs and vaccines. The P. falciparum genome is unusually A+T-rich, which hampers cloning and expressing these genes in heterologous systems for functional analysis. The large repertoire of genetic tools available for Saccharomyces cerevisiae makes this yeast an ideal system for large scale functional complementation analyses of parasite genes. Here, we report the construction of a cDNA library from P. knowlesi, which has a lower A+T content compared with P. falciparum. This library was applied in a yeast complementation assay to identify malaria genes involved in the decarboxylation of phosphatidylserine. Transformation of a psd1Deltapsd2Deltadpl1Delta yeast strain, defective in phosphatidylethanolamine synthesis, with the P. knowlesi library led to identification of a new parasite phosphatidylserine decarboxylase (PkPSD). Unlike phosphatidylserine decarboxylase enzymes from other eukaryotes that are tightly associated with membranes, the PkPSD enzyme expressed in yeast was equally distributed between membrane and soluble fractions. In vitro studies reveal that truncated forms of PkPSD are soluble and undergo auto-endoproteolytic maturation in a phosphatidylserine dependent reaction that is inhibited by other anionic phospholipids. This study defines a new system for probing the function of Plasmodium genes by library based genetic complementation and its usefulness in revealing new biochemical properties of encoded proteins. PMID- 22057269 TI - Poly(ADP-ribose) polymerase 1 (PARP-1) binds to 8-oxoguanine-DNA glycosylase (OGG1). AB - Human 8-oxoguanine-DNA glycosylase (OGG1) plays a major role in the base excision repair pathway by removing 8-oxoguanine base lesions generated by reactive oxygen species. Here we report a novel interaction between OGG1 and Poly(ADP-ribose) polymerase 1 (PARP-1), a DNA-damage sensor protein involved in DNA repair and many other cellular processes. We found that OGG1 binds directly to PARP-1 through the N-terminal region of OGG1, and this interaction is enhanced by oxidative stress. Furthermore, OGG1 binds to PARP-1 through its BRCA1 C-terminal (BRCT) domain. OGG1 stimulated the poly(ADP-ribosyl)ation activity of PARP-1, whereas decreased poly(ADP-ribose) levels were observed in OGG1(-/-) cells compared with wild-type cells in response to DNA damage. Importantly, activated PARP-1 inhibits OGG1. Although the OGG1 polymorphic variant proteins R229Q and S326C bind to PARP-1, these proteins were defective in activating PARP-1. Furthermore, OGG1(-/-) cells were more sensitive to PARP inhibitors alone or in combination with a DNA-damaging agent. These findings indicate that OGG1 binding to PARP-1 plays a functional role in the repair of oxidative DNA damage. PMID- 22057270 TI - Lzts2 regulates embryonic cell movements and dorsoventral patterning through interaction with and export of nuclear beta-catenin in zebrafish. AB - Leucine zipper tumor suppressor 2 (Lzts2) functions in the development and progression of various tumors, but its activities in vertebrate embryogenesis remain unclear. Here, we demonstrate that lzts2 transcripts are of maternal origin in zebrafish embryos. Activation of BMP signaling up-regulates zygotic expression of lzts2, whereas canonical Wnt signaling acts upstream of BMP signaling to inhibit lzts2 expression. Abrogation of lzts2 expression by its specific morpholino-enhanced gastrula convergence and extension (CE) movements, dorsalized early embryos, and inhibited specification of midline progenitors for pancreas, liver, and heart. In contrast, ectopic expression of lzts2 led to the delay of CE movements and midline convergence of organ progenitors and resulted in a certain ratio of ventralized embryos. Mechanistically, Lzts2 regulates the migration of embryonic cells and dorsoventral patterning through its limitation of Wnt/beta-catenin activity, because it physically interacts with beta-catenin-1 and -2 and transports them out of the nucleus. In addition, both beta-catenin-1 and -2 exhibit redundant functions in activation of Stat3 signaling and in induction of Wnt5/11 expression through inhibition of BMP signaling and stimulation of Cyclops and Squint expression. Thus, Lzts2 regulates gastrula CE movements, dorsoventral patterning, and midline convergence and specification of organ precursors through interaction with and the export of nuclear beta-catenins in zebrafish. PMID- 22057271 TI - Identification of a cAMP-response element in the regulator of G-protein signaling 2 (RGS2) promoter as a key cis-regulatory element for RGS2 transcriptional regulation by angiotensin II in cultured vascular smooth muscles. AB - Mice deficient in regulator of G-protein signaling-2 (RGS2) have severe hypertension, and RGS2 genetic variations occur in hypertensive humans. A potentially important negative feedback loop in blood pressure homeostasis is that angiotensin II (Ang II) increases vascular smooth muscle cell (VSMC) RGS2 expression. We reported that Group VIA phospholipase A(2) (iPLA(2)beta) is required for this response (Xie, Z., Gong, M. C., Su, W., Turk, J., and Guo, Z. (2007) J. Biol. Chem. 282, 25278-25289), but the specific molecular causes and consequences of iPLA(2)beta activation are not known. Here we demonstrate that both protein kinases C (PKC) and A (PKA) participate in Ang II-induced VSMC RGS2 mRNA up-regulation, and that actions of PKC and PKA precede and follow iPLA(2)beta activation, respectively. Moreover, we identified a conserved cAMP response element (CRE) in the murine RGS2 promoter that is critical for cAMP response element-binding protein (CREB) binding and RGS2 promoter activation. Forskolin-stimulated RGS2 mRNA up-regulation is inhibited by CREB sequestration or specific disruption of the CREB-RGS2 promoter interaction, and Ang II-induced CREB phosphorylation and nuclear localization are blocked by iPLA(2)beta pharmacologic inhibition or genetic ablation. Ang II-induced intracellular cyclic AMP accumulation precedes CREB phosphorylation and is diminished by inhibiting iPLA(2), cyclooxygenase, or lipoxygenase. Moreover, three single nucleotide polymorphisms identified in hypertensive patients are located in the human RGS2 promoter CREB binding site. Point mutations corresponding to these single nucleotide polymorphisms interfere with stimulation of human RGS2 promoter activity by forskolin. Our studies thus delineate a negative feedback loop to attenuate Ang II signaling in VSMC with potential importance in blood pressure homeostasis and the pathogenesis of human essential hypertension. PMID- 22057272 TI - (Na+ + K+)-ATPase is a target for phosphoinositide 3-kinase/protein kinase B and protein kinase C pathways triggered by albumin. AB - In recent decades, evidence has confirmed the crucial role of albumin in the progression of renal disease. However, the possible role of signaling pathways triggered by physiologic concentrations of albumin in the modulation of proximal tubule (PT) sodium reabsorption has not been considered. In the present work, we have shown that a physiologic concentration of albumin increases the expression of the alpha1 subunit of (Na(+) + K(+))-ATPase in LLC-PK1 cells leading to an increase in enzyme activity. This process involves the sequential activation of PI3K/protein kinase B and protein kinase C pathways promoting inhibition of protein kinase A. This integrative network is inhibited when albumin concentration is increased, similar to renal disease, leading to a decrease in the alpha1 subunit of (Na(+) + K(+))-ATPase expression. Together, the results indicate that variation in albumin concentration in PT cells has an important effect on PT sodium reabsorption and, consequently, on renal sodium excretion. PMID- 22057273 TI - Real-time imaging reveals that P2Y2 and P2Y12 receptor agonists are not chemoattractants and macrophage chemotaxis to complement C5a is phosphatidylinositol 3-kinase (PI3K)- and p38 mitogen-activated protein kinase (MAPK)-independent. AB - Adenosine 5'-triphosphate (ATP) has been implicated in the recruitment of professional phagocytes (neutrophils and macrophages) to sites of infection and tissue injury in two distinct ways. First, ATP itself is thought to be a chemotactic "find me" signal released by dying cells, and second, autocrine ATP signaling is implicated as an amplifier mechanism for chemotactic navigation to end-target chemoattractants, such as complement C5a. Here we show using real-time chemotaxis assays that mouse peritoneal macrophages do not directionally migrate to stable analogs of ATP (adenosine-5'-(gamma-thio)-triphosphate (ATPgammaS)) or its hydrolysis product ADP (adenosine-5'-(beta-thio)-diphosphate (ADPbetaS)). HPLC revealed that these synthetic P2Y(2) (ATPgammaS) and P2Y(12) (ADPbetaS) receptor ligands were in fact slowly degraded. We also found that ATPgammaS, but not ADPbetaS, promoted chemokinesis (increased random migration). Furthermore, we found that photorelease of ATP or ADP induced lamellipodial membrane extensions. At the cell signaling level, C5a, but not ATPgammaS, activated Akt, whereas both ligands induced p38 MAPK activation. p38 MAPK and Akt activation are strongly implicated in neutrophil chemotaxis. However, we found that inhibitors of phosphatidylinositol 3-kinase (PI3K; upstream of Akt) and p38 MAPK (or conditional deletion of p38alpha MAPK) did not impair macrophage chemotactic efficiency or migration velocity. Our results suggest that PI3K and p38 MAPK are redundant for macrophage chemotaxis and that purinergic P2Y(2) and P2Y(12) receptor ligands are not chemotactic. We propose that ATP signaling is strictly autocrine or paracrine and that ATP and ADP may act as short-range "touch me" (rather than long-range find me) signals to promote phagocytic clearance via cell spreading. PMID- 22057274 TI - Plasticity in interactions of fibroblast growth factor 1 (FGF1) N terminus with FGF receptors underlies promiscuity of FGF1. AB - Tissue-specific alternative splicing in the second half of Ig-like domain 3 (D3) of fibroblast growth factor receptors 1-3 (FGFR1 to -3) generates epithelial FGFR1b-FGFR3b and mesenchymal FGFR1c-FGFR3c splice isoforms. This splicing event establishes a selectivity filter to restrict the ligand binding specificity of FGFRb and FGFRc isoforms to mesenchymally and epithelially derived fibroblast growth factors (FGFs), respectively. FGF1 is termed the "universal FGFR ligand" because it overrides this specificity barrier. To elucidate the molecular basis for FGF1 cross-reactivity with the "b" and "c" splice isoforms of FGFRs, we determined the first crystal structure of FGF1 in complex with an FGFRb isoform, FGFR2b, at 2.1 A resolution. Comparison of the FGF1-FGFR2b structure with the three previously published FGF1-FGFRc structures reveals that plasticity in the interactions of the N-terminal region of FGF1 with FGFR D3 is the main determinant of FGF1 cross-reactivity with both isoforms of FGFRs. In support of our structural data, we demonstrate that substitution of three N-terminal residues (Gly-19, His-25, and Phe-26) of FGF2 (a ligand that does not bind FGFR2b) for the corresponding residues of FGF1 (Phe-16, Asn-22, and Tyr-23) enables the FGF2 triple mutant to bind and activate FGFR2b. These findings taken together with our previous structural data on receptor binding specificity of FGF2, FGF8, and FGF10 conclusively show that sequence divergence at the N termini of FGFs is the primary regulator of the receptor binding specificity and promiscuity of FGFs. PMID- 22057275 TI - Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. AB - Recent demonstrations that the secretion, uptake, and interneuronal transfer of tau can be modulated by disease-associated tau modifications suggest that secretion may be an important element in tau-induced neurodegeneration. Here, we show that much of the tau secreted by M1C cells occurs via exosomal release, a widely characterized mechanism that mediates unconventional secretion of other aggregation-prone proteins (alpha-synuclein, prion protein, and beta-amyloid) in neurodegenerative disease. Exosome-associated tau is also present in human CSF samples and is phosphorylated at Thr-181 (AT270), an established phosphotau biomarker for Alzheimer disease (AD), in both M1C cells and in CSF samples from patients with mild (Braak stage 3) AD. A preliminary analysis of proteins co purified with tau in secreted exosomes identified several that are known to be involved in disease-associated tau misprocessing. Our results suggest that exosome-mediated secretion of phosphorylated tau may play a significant role in the abnormal processing of tau and in the genesis of elevated CSF tau in early AD. PMID- 22057276 TI - Nuclear localization of de novo thymidylate biosynthesis pathway is required to prevent uracil accumulation in DNA. AB - Uracil accumulates in DNA as a result of impaired folate-dependent de novo thymidylate biosynthesis, a pathway composed of the enzymes serine hydroxymethyltransferase (SHMT), thymidylate synthase (TYMS), and dihydrofolate reductase. In G1, this pathway is present in the cytoplasm and at S phase undergoes small ubiquitin-like modifier-dependent translocation to the nucleus. It is not known whether this pathway functions in the cytoplasm, nucleus, or both in vivo. SHMT1 generates 5,10-methylenetetrahydrofolate for de novo thymidylate biosynthesis, a limiting step in the pathway, but also tightly binds 5 methyltetrahydrofolate in the cytoplasm, a required cofactor for homocysteine remethylation. Overexpression of SHMT1 in cell cultures inhibits folate-dependent homocysteine remethylation and enhances thymidylate biosynthesis. In this study, the impact of increased Shmt1 expression on folate-mediated one-carbon metabolism was determined in mice that overexpress the Shmt1 cDNA (Shmt1tg+ mice). Compared with wild type mice, Shmt1tg+ mice exhibited elevated SHMT1 and TYMS protein levels in tissues and evidence for impaired homocysteine remethylation but surprisingly exhibited depressed levels of nuclear SHMT1 and TYMS, lower rates of nuclear de novo thymidylate biosynthesis, and a nearly 10-fold increase in uracil content in hepatic nuclear DNA when fed a folate- and choline-deficient diet. These results demonstrate that SHMT1 and TYMS localization to the nucleus is essential to prevent uracil accumulation in nuclear DNA and indicate that SHMT1 mediated nuclear de novo thymidylate synthesis is critical for maintaining DNA integrity. PMID- 22057277 TI - The Src family kinase Fyn mediates hyperosmolarity-induced Mrp2 and Bsep retrieval from canalicular membrane. AB - In perfused rat liver, hyperosmolarity induces Mrp2- (Kubitz, R., D'urso, D., Keppler, D., and Haussinger, D. (1997) Gastroenterology 113, 1438-1442) and Bsep retrieval (Schmitt, M., Kubitz, R., Lizun, S., Wettstein, M., and Haussinger, D. (2001) Hepatology 33, 509-518) from the canalicular membrane leading to cholestasis. The aim of this study was to elucidate the underlying signaling events. Hyperosmolarity-induced retrieval of Mrp2 and Bsep from the canalicular membrane in perfused rat liver was accompanied by an activating phosphorylation of the Src kinases Fyn and Yes but not of c-Src. Both hyperosmotic transporter retrieval and Src kinase activation were sensitive to apocynin (300 MUmol/liter), N-acetylcysteine (NAC; 10 mmol/liter), and SU6656 (1 MUmol/liter). Also PP-2 (250 nmol/liter), which inhibited hyperosmotic Fyn but not Yes activation, prevented hyperosmotic transporter retrieval from the canalicular membrane, suggesting that Fyn but not Yes mediates hyperosmotic Bsep and Mrp2 retrieval. Neither hyperosmotic Fyn activation nor Bsep/Mrp2 retrieval was observed in livers from p47(phox) knock-out mice. Hyperosmotic activation of JNKs was sensitive to apocynin and NAC but insensitive to SU6656 and PP-2, indicating that JNKs are not involved in transporter retrieval, as also evidenced by experiments using the JNK inhibitors L-JNKI-1 and SP6001255, respectively. Hyperosmotic transporter retrieval was accompanied by a NAC and Fyn knockdown-sensitive inhibition of biliary excretion of the glutathione conjugate of 1-chloro-2,4-dinitrobenzene in perfused rat liver and of cholyl-L-lysyl-fluorescein secretion into the pseudocanaliculi formed by hepatocyte couplets. Hyperosmolarity triggered an association between Fyn and cortactin and increased the amount of phosphorylated cortactin underneath the canalicular membrane. It is concluded that the hyperosmotic cholestasis is triggered by a NADPH oxidase-driven reactive oxygen species formation that mediates Fyn-dependent retrieval of the Mrp2 and Bsep from the canalicular membrane, which may involve an increased cortactin phosphorylation. PMID- 22057278 TI - Relative spatial positions of tryptophan and cationic residues in helical membrane-active peptides determine their cytotoxicity. AB - The cytotoxic activity of 10 analogs of the idealized amphipathic helical 21-mer peptide (KAAKKAA)3, where three of the Ala residues at different positions have been replaced with Trp residues, has been investigated. The peptide's cytotoxic activity was found to be markedly dependent upon the position of the Trp residues within the hydrophobic sector of an idealized alpha-helix. The peptides with Trp residues located opposite the cationic sector displayed no antitumor activity, whereas those peptides with two or three Trp residues located adjacent to the cationic sector exhibited high cytotoxic activity when tested against three different cancer cell lines. Dye release experiments revealed that in contrast to the peptides with Trp residues located opposite the cationic sector, the peptides with Trp residues located adjacent to the cationic sector induced a strong permeabilizing activity from liposomes composed of a mixture of zwitterionic phosphatidylcholine and negatively charged phosphatidylserine (1-palmitoyl-2 oleoyl-sn-glycero-3-phosphocholine (POPC)/1-palmitoyl-2-oleoyl-sn-glycero-3 phospho-l-serine (POPS)) (2:1) but not from liposomes composed of zwitterionic phosphatidylcholine, POPC. Fluorescence blue shift and quenching experiments revealed that Trp residues inserted deeper into the hydrophobic environment of POPC/POPS liposomes for peptides with high cytotoxic activity. Through circular dichroism studies, a correlation between the cytotoxic activity and the alpha helical propensity was established. Structural studies of one inactive and two active peptides in the presence of micelles using NMR spectroscopy showed that only the active peptides adopted highly coiled to helical structures when bound to a membrane surface. PMID- 22057279 TI - Effect of Microcystis aeruginosa on the rotifer Brachionus calyciflorus at different temperatures. AB - Rotifers are one of the smallest metazoans. They serve as a model organism for ecotoxicological studies. More than 60% of the lakes in China are increasingly eutrophic and they are susceptible to blooms of Microcystis aeruginosa. We investigated the effects of M. aeruginosa on the survival and reproduction of Brachionus calyciflorus using the life table method at different temperatures. The findings showed that concentration of M. aeruginosa significantly affected the intrinsic rate of increase (r(m)), net reproductive rate (R(0)), average lifespan (L) and offspring number (p < 0.05). Temperature also significantly affected the generation time (T), average lifespan (L) and offspring number (p < 0.05). Moreover, the interaction between temperature and concentration had statistically significant effects on offspring number (p < 0.05). M. aeruginosa suppressed the survival and reproduction of B. calyciflorus, particularly at a concentration of 10(6) cells/mL. The r(m) values of the rotifers exposed at 10(6) cells/mL decreased more than 200% compared with those of the control group. However, at a lower concentration, 10(4) cells/mL, M. aeruginosa may supply appropriate nourishment to rotifers. In addition, at concentrations of 10(5) and 10(6) cells/mL, the inhibition of rotifers by M. aeruginosa heightened with increasing temperature. PMID- 22057280 TI - Persistence behavior of combination mix crop protection agents in/on eggplant fruits. AB - Persistence behavior of two combination mix formulations of insecticides viz. profenofos + cypermethrin (Roket 44EC) and chlorpyrifos + cypermethrin (Nacraj 505) were studied in eggplant fruits following spray application at recommended and double dose. Half-life values were calculated from first order dissipation kinetics, in case of Roket 44EC, residues of cypermethrin on fruits dissipated with half-life of 2.15-2.31 days, whereas residues of profenofos dissipated with the half-life of 0.91-1.86 days. Profenofos residues persisted beyond 7 days in soil, whereas residues of cypermethrin were below detection limit on 0-day itself. Dissipation of chlorpyrifos residues in the combination mix with cypermethrin (Nacraj-505) followed first order kinetics with the half-life values of 3.27-3.10 days. In soil, chlorpyrifos residues were below detectable limit even on 0-day at recommended dose of application. More than 90% dissipation was recorded on 7 day, although residues persisted beyond 15 days at double the recommended dose. Half life of dissipation for cypermethrin calculated from first order dissipation kinetics varied from 2.19 to 3.27 days. In soil, no residues of cypermethrin were detected even on 0-day at recommended dose. PMID- 22057281 TI - Coartemether induced oxidative and hepatic damage in Plasmodium berghei strain Anka infected mice. AB - This study investigated the effect of coartemether on antioxidant and hepatotoxic biomarkers in Plasmodium berghei infected mice. Erythrocyte, hepatic and renal superoxide dismutase (2.71 +/- 0.51; 1.96 +/- 0.87; 2.84 +/- 0.22 Units/mg protein respectively) and catalase (4.10 +/- 0.10; 8.25 +/- 1.24; 6.28 +/- 0.11 Units/mg protein respectively) activities were significantly (p < 0.05) elevated in "parasitized and treated" (PnT) animals. Renal glutathione level (19.02 +/- 0.20 MUg/mL) was elevated in PnT animals. Glutathione S-transferase and malondialdehyde levels in hepatic (8.76 +/- 0.49 MUmol/min/mg; 527.23 +/- 24.56 mmol/dL) and renal (3.35 +/- 0.30 MUmol/min/mg; 464.42 +/- 59.13 mmol/dL) tissues were significantly high (p < 0.05) in coartemether-treated animals alone. Plasma aspartate transferase (9.45 +/- 3.59 U/L) and alanine transferase (5.78 +/- 2.36 U/L) were high in PnT animals. Therefore, data indicates that in the presence of P. berghei, coartemether could alter the antioxidant status and induce hepatotoxic damage in mice. PMID- 22057282 TI - Up-regulated expression of advanced glycation end-products and their receptor in the small intestine and colon of diabetic rats. AB - BACKGROUND AND AIMS: Gastrointestinal disorders and symptoms are common in diabetic patients. Advanced glycation end-products (AGEs) and their receptor (RAGE) have been proposed as an important pathological mechanism underlying diabetic complications, such as diabetic cardiopathy, retinopathy, nephropathy, etc. The aims were to study the distribution of AGE and RAGE in the normal and diabetic small intestine and colon in rats and the possible relationship between AGEs/RAGE and diabetes-induced intestinal structural remodeling. METHODS: Diabetic and age-matched normal rats survived for 56 days. The body weight and blood glucose were measured regularly until day 56. Jejunal, ileal, and colonic segments were excised. The wet weight per unit length and the layer thickness were measured. AGE and RAGE were detected by immunohistochemical staining. RESULTS: The wet weight per unit length in the three segments and the layer thickness in jejunum and ileum increased in the diabetic rats. The staining density of AGE in diabetic rats was higher in the villi of jejunum and ileum, and in the crypt and circumferential muscle layer of ileum compared to normal rats. The staining intensity of RAGE increased in ganglia, crypt, and brush border of diabetic jejunum and ileum as well as in ganglia of diabetic colon. Positive association was found between the accumulation of AGE and RAGE and the thickness of the different layers. CONCLUSIONS: The expression of AGE and RAGE is up regulated in the small intestine and colon of diabetic rats. The increased AGE and RAGE levels may contribute to diabetic GI dysfunction. PMID- 22057283 TI - Outcome predictors for thiopurine maintenance therapy in patients with Crohn's disease. AB - BACKGROUND: Little is known about the factors that predict clinical relapse in Crohn's disease patients receiving thiopurine therapy to maintain remission. The objective of this study was, therefore, to investigate these factors. METHODS: A total of 82 Crohn's disease patients who received their first course of azathioprine or 6-mercaptopurine treatment at Severance Hospital between June 1996 and July 2007 were recruited to the study. During the follow-up period (25.5 +/- 16.6 months) 19 patients (23.2%) discontinued the medication because of significant adverse effects. Forty-five patients who continued to receive thiopurines to maintain medically or surgically induced remission were enrolled in the study. After adjusting the maintenance dose, patients in remission were followed at 2-3 month intervals. Relapse was defined as a Crohn's disease activity index >= 150. RESULTS: The male-to-female ratio was 1.5:1 and the mean age was 26.3 +/- 7.1 years. Cumulative relapse was 18.0% after one year and 49.2% after three years. According to multivariate Cox regression analysis, younger age (<30 years) at thiopurine therapy and increased C-reactive protein level (>= 0.5 mg/dL) at remission were independent predictors of relapse (hazard ratio 19.751, 95%-confidence interval (CI) 1.996-195.402, P = 0.011 and hazard ratio 9.001, 95% CI 1.583-51.181, P = 0.013, respectively). CONCLUSIONS: Younger age (<30 years) and increased C-reactive protein level at remission were independent predictors of relapse in Crohn's disease patients receiving thiopurines to maintain remission. These high-risk groups warrant closer observation and possibly early introduction of biological agents. PMID- 22057284 TI - Lewis score correlates more closely with fecal calprotectin than Capsule Endoscopy Crohn's Disease Activity Index. AB - BACKGROUND: Small-bowel capsule endoscopy (SBCE) is an invaluable imaging method for the small bowel. The Lewis score (LS) and the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) have been developed to standardize the reporting of small-bowel inflammation. Fecal calprotectin (FC) represents a highly reliable biomarker of intestinal inflammation. AIM: To assess the performance of the two SBCE inflammation scoring systems by correlating them with FC. Furthermore, to define threshold levels for CECDAI. METHODS: Retrospective study; patients who underwent SBCE and had FC measurement shortly before or after SBCE. LS and CECDAI were calculated by a single reviewer and correlated [Spearman's (r ( s ))] with the FC results. Linear regression analysis was used to identify threshold levels for CECDAI. RESULTS: Forty-nine patients; three subgroups A, B and C (based on FC levels <100, 100-200, and >=200 MUg/g, respectively). LS appears to correlate with FC (r ( s ) = 0.448, p = 0.0014), unlike CECDAI, which does not demonstrate significant correlation (r ( s ) = 0.245, p = 0.089). Strongly positive correlation between FC and LS was observed in subgroup A (r ( s ) = 0.68, p = 0.0047), while in subgroups B and C, neither LS nor CECDAI showed correlation with FC. Significant correlation between LS and CECDAI was demonstrated (r ( s ) = 0. 6324, p < 0.0001). Linear regression analysis demonstrates that LS thresholds of 135 and 790 correspond with CECDAI levels of 3.8 and 5.8, respectively. CONCLUSIONS: LS performs better than CECDAI in describing small bowel inflammation, especially at FC levels of <100 MUg/g. Furthermore, CECDAI levels of 3.8 and 5.8 seem to correspond to LS thresholds of 135 and 790, respectively. PMID- 22057285 TI - Photodynamic therapy for unresectable cholangiocarcinoma. AB - Cholangiocarcinoma (CC) is a rare primary malignancy of the biliary tract with a dismal prognosis. Curative resection can only be applied to a small proportion of early diagnosed patients. Palliative biliary drainage by either percutaneous or endoscopic insertion of endoprostheses improves quality-of-life by reducing pruritis, cholangitis, and pain, but has been reported to improve survival time only slightly. Photodynamic therapy (PDT) is a relatively new local, minimally invasive palliative strategy for unresectable CC. PDT uses a photosensitive molecule that accumulates in proliferating tissue such as tumors. Activation of the photosensitizer by use of light of a specific wavelength generates reactive oxygen species leading to selective tumor-cell death. After initial feasibility studies and promising prospective phase II studies, results from two prospective randomized controlled trials comparing PDT after endoprostheses insertion with endoprostheses alone for patients with unresectable CC have been published. One study resulted in dramatically prolonged median survival in the PDT group (493 days) compared with the non-PDT group (98 days) (P < 0.0001), and significantly improved performance status (PS) in the PDT group. A second study with high baseline patients' PS confirmed the benefit of PDT for survival (630 days in the PDT group compared with 210 days for endoprostheses alone, P < 0.01). The procedures were generally well tolerated. PDT has also been reported to have a favorable outcome as adjuvant and neoadjuvant therapy for CC. Although accumulated data and local expertise are limited, PDT can be regarded as a standard palliative therapy for unresectable CC. PMID- 22057286 TI - Prospective assessment of risk of bacteremia following colorectal stent placement. AB - BACKGROUND: Colorectal stent insertion is an invasive endoscopic procedure. However, there are no reports regarding the incidence of bacteremia with colorectal stent. OBJECTIVE: This study was to evaluate the risk of bacteremia and infectious complications after stent insertion for colorectal obstruction. METHODS: Patients who underwent colorectal stent insertion were enrolled consecutively. Blood cultures were obtained before colorectal stent insertion and at 30 min after the procedure. Patients were monitored for 48 h after colorectal stent insertion to detect the development of infectious complications. Procedural data collected included location of obstruction, degree of bowel preparation, obstructive symptoms, and the time required for the procedure. RESULTS: Of 64 patients undergoing colorectal stent, four (6.3%) had a positive post-stent blood culture. All patients, including those with positive cultures, remained asymptomatic during the 48 h after the procedure. Site of obstruction, degree of bowel preparation, age, and underlying disease were not different between the two groups. Development of bacteremia was associated with long procedure time (p < 0.05). CONCLUSIONS: Colorectal stent insertion does not induce significant bacteremia in patients with colorectal obstruction. These findings suggest that the routine use of prophylactic antibiotics may not be necessary in colorectal stent insertion. PMID- 22057287 TI - Anxiety online: a virtual clinic: preliminary outcomes following completion of five fully automated treatment programs for anxiety disorders and symptoms. AB - BACKGROUND: The development of e-mental health interventions to treat or prevent mental illness and to enhance wellbeing has risen rapidly over the past decade. This development assists the public in sidestepping some of the obstacles that are often encountered when trying to access traditional face-to-face mental health care services. OBJECTIVE: The objective of our study was to investigate the posttreatment effectiveness of five fully automated self-help cognitive behavior e-therapy programs for generalized anxiety disorder (GAD), panic disorder with or without agoraphobia (PD/A), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (SAD) offered to the international public via Anxiety Online, an open-access full-service virtual psychology clinic for anxiety disorders. METHODS: We used a naturalistic participant choice, quasi-experimental design to evaluate each of the five Anxiety Online fully automated self-help e-therapy programs. Participants were required to have at least subclinical levels of one of the anxiety disorders to be offered the associated disorder-specific fully automated self-help e-therapy program. These programs are offered free of charge via Anxiety Online. RESULTS: A total of 225 people self-selected one of the five e-therapy programs (GAD, n = 88; SAD, n = 50; PD/A, n = 40; PTSD, n = 30; OCD, n = 17) and completed their 12 week posttreatment assessment. Significant improvements were found on 21/25 measures across the five fully automated self-help programs. At postassessment we observed significant reductions on all five anxiety disorder clinical disorder severity ratings (Cohen d range 0.72-1.22), increased confidence in managing one's own mental health care (Cohen d range 0.70-1.17), and decreases in the total number of clinical diagnoses (except for the PD/A program, where a positive trend was found) (Cohen d range 0.45-1.08). In addition, we found significant improvements in quality of life for the GAD, OCD, PTSD, and SAD e-therapy programs (Cohen d range 0.11-0.96) and significant reductions relating to general psychological distress levels for the GAD, PD/A, and PTSD e-therapy programs (Cohen d range 0.23-1.16). Overall, treatment satisfaction was good across all five e-therapy programs, and posttreatment assessment completers reported using their e-therapy program an average of 395.60 (SD 272.2) minutes over the 12-week treatment period. CONCLUSIONS: Overall, all five fully automated self-help e therapy programs appear to be delivering promising high-quality outcomes; however, the results require replication. PMID- 22057288 TI - Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells. AB - The transcriptional repressor Blimp-1 promotes the differentiation of CD8(+) T cells into short-lived effector cells (SLECs) that express the lectin-like receptor KLRG-1, but how it operates remains poorly defined. Here we show that Blimp-1 bound to and repressed the promoter of the gene encoding the DNA-binding inhibitor Id3 in SLECs. Repression of Id3 by Blimp-1 was dispensable for SLEC development but limited the ability of SLECs to persist as memory cells. Enforced expression of Id3 was sufficient to restore SLEC survival and enhanced recall responses. Id3 function was mediated in part through inhibition of the transcriptional activity of E2A and induction of genes regulating genome stability. Our findings identify the Blimp-1-Id3-E2A axis as a key molecular switch that determines whether effector CD8(+) T cells are programmed to die or enter the memory pool. PMID- 22057289 TI - The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. AB - During infection, naive CD8(+) T cells differentiate into effector cells, which are armed to eliminate pathogens, and memory cells, which are poised to protect against reinfection. The transcriptional program that regulates terminal differentiation into short-lived effector-memory versus long-lived memory cells is not clearly defined. Through the use of mice expressing reporters for the DNA binding inhibitors Id2 and Id3, we identified Id3(hi) precursors of long-lived memory cells before the peak of T cell population expansion or upregulation of cell-surface receptors that indicate memory potential. Deficiency in Id2 or Id3 resulted in loss of distinct CD8(+) effector and memory populations, which demonstrated unique roles for these inhibitors of E-protein transcription factors. Furthermore, cytokines altered the expression of Id2 and Id3 differently, which provides insight into how external cues influence gene expression. PMID- 22057290 TI - The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation. AB - Chronic inflammation has been strongly associated with tumor progression, but the underlying mechanisms remain elusive. Here we demonstrate that E3 ligase Itch and deubiquitinase Cyld formed a complex via interaction through 'WW-PPXY' motifs. The Itch-Cyld complex sequentially cleaved Lys63-linked ubiquitin chains and catalyzed Lys48-linked ubiquitination on the kinase Tak1 to terminate inflammatory signaling via tumor necrosis factor. Reconstitution of wild-type Cyld but not the mutant Cyld(Y485A), which cannot associate with Itch, blocked sustained Tak1 activation and proinflammatory cytokine production by Cyld(-/-) bone marrow-derived macrophages. Deficiency in Itch or Cyld led to chronic production of tumor-promoting cytokines by tumor-associated macrophages and aggressive growth of lung carcinoma. Thus, we have identified an Itch-Cyld mediated regulatory mechanism in innate inflammatory cells. PMID- 22057291 TI - Global concepts of bladder pain syndrome (interstitial cystitis). AB - BACKGROUND: Bladder pain syndrome (BPS), commonly referred to as "interstitial cystitis", is no longer considered a rare disorder. It may affect up to 2.7% of the adult female population (Ueda et al. in Int J Urol 10:1-70, 2003) with up to 20% of cases occurring in men. METHODS: The last two decades have seen a worldwide effort to try to standardize its nomenclature, definition, diagnosis, and treatment algorithm. The literature has been reviewed. RESULTS: In this article, we will detail current terminology, diagnostic approaches and treatment. Standard therapies will be discussed, and a section that concentrates on the management of the subset of patients with a Hunner's lesion will be highlighted. CONCLUSIONS: BPS is today viewed through a new paradigm. It is no longer considered primarily a bladder disease, but rather one of a number of chronic pain syndromes that is distinguished by being manifest through bladder-related symptoms. A distinct subgroup of patients with Hunner's lesion has specific characteristics, and successful treatment of this subgroup is available. PMID- 22057292 TI - A phosphino-oxazoline ligand as a P,N-bridge in palladium/cobalt or P,N-chelate in nickel complexes: catalytic ethylene oligomerization. AB - The Pd(II) complex [PdCl(2)(1)] [1 = ({oxazolin-2-yl}methyl)diphenylphosphine] was obtained by the 1:1 reaction of 1 with [PdCl(2)(NCPh)(2)]. Although this neutral complex is stable in the solid-state and in solution, it reacts with the dinuclear complex [CoCl(2)(MU-1)](2) to afford the heterometallic zwitterionic complex [{PdCl(1)}(+)(MU-1)(CoCl(3))(-)] (2). Under inert atmosphere, two equivalents of 1 reacted with [NiCl(2)(dme)] to give trans-[NiCl(2)(1)(2)] (3) in CH(2)Cl(2) but cis-[NiCl(2)(1)(2)] (4) in CHCl(3). When the latter reaction was performed in air, trans-[NiCl(2)(5)(2)] (6) [5 = ({oxazolin-2 yl}methyl)diphenylphosphine oxide] was obtained. All metal complexes, 2, 3, 4 and 6, have been structurally characterized by X-ray diffraction. Complexes 3, 4 and 6 have been evaluated as precatalysts for ethylene oligomerisation in the presence of AlEtCl(2) as cocatalyst. Complexes 3 and 6 yielded a turnover frequency (TOF) of 60,700 and 62,600 mol of C(2)H(4)/((mol of Ni).h), respectively, in the presence of 10 equiv. of AlEtCl(2). In the presence of only 6 equiv. of cocatalyst, these Ni complexes yielded TOF values of 41,500 and 58,000 mol of C(2)H(4)/((mol of Ni).h), respectively. PMID- 22057293 TI - Melamine-related urinary stones in 195 infants and young children: clinical features within 2 years of follow-up. AB - OBJECTIVE: To summarize the clinical features and follow-up, the effects of melamine-tainted milk powder (MMP) consumption on kidney and body growth in children who suffered from melamine-related urinary stones (MUS) 2 years earlier were checked. MEASUREMENTS: Body height and weight, kidney and bladder morphology monitored by ultrasound, urinalysis and renal function were recorded. Plain abdominal radiography was performed for differential diagnosis. The first follow up was carried out at 15 months and the second 2 years later for patients who showed any abnormality at the first follow-up. Two hundred age- and gender matched cohorts were included. RESULTS: All cases received conservative treatment in hospital. Fifteen months of follow-up was successfully carried out in 167 cases. 91 children had residual MUS at the time of discharge, 58 MUS disappeared completely, 25 dissolved partially, 1 increased in size, and 7 did not change. At 2 years of follow-up, the residual stones all disappeared except for 1 case; the patient who showed a delayed development with regard to height caught up at 24 months of follow-up. CONCLUSIONS: Conservative treatment shows a high effectiveness in cases with residual MUS. Consumption of MMP with timely treatment did not demonstrate an evident impact on kidney and bladder although body height is slightly affected in a few cases. PMID- 22057294 TI - Investigation and development of quantum dot-encoded microsphere bioconjugates for DNA detection by flow cytometry. AB - The development of screening assays continues to be an active area of research in molecular diagnostics. Fluorescent microspheres conjugated to biomarkers (nucleic acids, proteins, lipids, carbohydrates) and analyzed on flow cytometer instruments offered a new approach for multiplexed detection platform in a suspension format. Quantum dots encoded into synthetic microspheres have the potentials to improve current screening bioassays and specifically suspension array technology. In this paper, commercialized quantum dot-encoded microsphere were evaluated and optimized as fluorescent probes to address some of the limitations of suspension array technologies. A comprehensive study was undertaken to adapt the bioconjugation procedure to the quantum dot-encoded microsphere structural and optical properties. Both the leaching-out of quantum dots and microspheres degradation under bioconjugation experimental conditions were minimized. A rapid, efficient and reproducible conjugation method was developed for the detection of single-stranded DNA with the commercialized quantum dot-encoded microsphere. Approximately ten thousand microspheres were conjugated to short amino-modified DNA sequences in one hour with high efficiency. The bioconjugated microspheres acting as fluorescent probes successfully detected a DNA target in suspension with high specificity. Quantum dot-encoded microsphere commercial products are limited which strongly prevents reproducible and comparative studies between laboratories. The method developed here contributes to the understanding of quantum dot-encoded microsphere reactivity, and to the optimization of adapted experimental procedure. This step is essential in the development of this new fluorescent probe technology for multiplex genotyping assay and molecular diagnostic applications. PMID- 22057296 TI - Predictive models for tuberculous pleural effusions in a high tuberculosis prevalence region. AB - BACKGROUND: Patients with pleural effusions who reside in geographic areas with a high prevalence of tuberculosis frequently have similar clinical manifestations of other diseases. The aim of our study was to develop a simple but accurate clinical score for differential diagnosis of tuberculosis pleural effusion (TPE) from non-TB pleural effusion (NTPE). METHODS: This was an unblinded, prospective study of Turkish patients 18 years of age or older with pleural effusion of indeterminate etiology conducted from June 2003 to June 2005. Unconditional logistic regression models were used to discriminate TPE cases from NTPE cases. Standard errors for the area under the curve (AUC) were calculated using the Mann Whitney method. Data were statistically significance if two-tailed P < 0.05. RESULTS: A total of 63.3% (157/248) of the patients had TPE while 36.7% (91/248) of the patients had other etiologies for pleural effusions. We were able to provide a predictive model of TPE that included age <47 years and either pleural fluid adenosine deaminase enzyme (PADA) >35 U/l or pleural serum protein ratio >0.710. However, only the combination of age <47 and PADA >35 U/l was significant (odds ratio [OR]: 7.46; 95% confidence interval [CI]: 3.99-13.96). The generated summary score (range = 0-6) was significantly predictive of TPE (OR: 2.91; 95% CI: 2.18-3.89) and with high AUC (0.79). CONCLUSION: We propose an affordable model that includes age <47 years and PADA >35 U/l for timely diagnosis of TPE in geographical regions with a high prevalence of TB. PMID- 22057297 TI - The synthesis and spectral properties of a stimuli-responsive D-pi-A charge transfer dye based on indole donor and dicyanomethylene acceptor moiety. AB - A dual mode chemosensor dye 3 for detection of fluoride ion, based on the D-pi-A molecular framework by one-step condensation, presents high selectivity and sensitivity both in colorimetric and fluorometric analyses. Upon the addition of F(-) anion, the absorption band shows a remarkable red shift along with fluorescent intensity decreasing. The absorption and fluorescent intensities of the dye 3 can be reversibly selected by deprotonation/protonation of the amine moiety via control of intramolecular charge transfer (ICT), leading to a molecular switch with "on" and "off" states. (1)H NMR titration analysis and DMol(3) calculation were employed to reveal the intermolecular charge transfer system of dye 3-F(-) complex. PMID- 22057298 TI - Synthesis, structural determination and spectroscopic analysis of a novel 2D terbium coordination network with ethyleneglycol-bis-(2-aminoethylether) N,N,N',N'-tetraacetic acid. AB - A novel two-dimensional (2D) mononuclear complex, namely, (enH(2))[Tb(III)(egta)(H(2)O)](2).6H(2)O (H(4)egta=ethyleneglycol-bis-(2 aminoethylether)-N,N,N',N'-tetraacetic acid and en=ethylenediamine), was successfully synthesized and characterized by infrared spectrum, UV-vis spectrum, fluorescence spectrum, thermal analysis and single-crystal X-ray diffraction techniques. Single-crystal X-ray diffraction analysis reveals that the central Tb(III) ion is nine-coordinate in geometry of pseudo-monocapped square antiprismatic polyhedron. Furthermore, the hydrogen bonds play an important role in the fabrication of layer structure of the complex. Through hydrogen bonds between ethylenediamine cation (enH(2)(2+)) and [Tb(III)(egta)(H(2)O)](-) complex anion, the title complex forms a 2D layer network along [111] crystallographic direction. Particularly, the fluorescent property is also fully investigated, which indicates that the title complex would be a potential candidate as fluorescent materials. PMID- 22057299 TI - Sticking probability of CN(X2Sigma+) radicals onto amorphous carbon nitride films formed from the decomposition of BrCN induced by the microwave discharge flow of Ar. AB - The sticking probability, s, of CN(X(2)Sigma(+)) radicals onto amorphous carbon nitride (a-CN(x)) films with high [N]/([N]+[C]) ratios (<=0.5) was evaluated. CN(X(2)Sigma(+)) radicals were generated from the decomposition of BrCN with the microwave discharge flow of Ar in the two experimental configurations, I and II, where the distance between the tip of the nozzle introducing BrCN is close (~10 mm) to and distant (~0.3 m) from the laser-beam path or the Si substrate, respectively. For each configuration, s was evaluated both under the desiccated and H(2)O-added conditions from the number density of CN(X(2)Sigma(+)) evaluated from the intensity of the CN(A(2)Pi(i)-X(2)Sigma(+)) laser-induced fluorescence spectrum calibrated against Rayleigh scattering intensity of Ar, the flow speed measured by a time-resolved emission, and the film mass. The [N]/([N]+[C]) ratios of films were evaluated as 0.4-0.5 and 0.3 in the configurations I and II, respectively, from the compositional analysis using Rutherford back scattering and elastic recoil detection analysis together with the XPS analysis. The variation of s under various experimental conditions was discussed based on the electron densities in the reaction region and the relative density of the hydrogen-termination structures of the film surface. PMID- 22057300 TI - Physicochemical study and characterization of the trimethoprim/2-hydroxypropyl gamma-cyclodextrin inclusion complex. AB - Here we report the preparation of a trimethoprim/2-hydroxypropyl-gamma cyclodextrin inclusion complex along with a physicochemical study, structural characterization, and molecular modeling of the complex. As main results, we observed from phase-solubility studies at two temperatures (20 degrees C and 35 degrees C) that the association constants decrease with increasing temperature. Values for K(1:1) constant were of the same magnitude order of those found for the parent gamma-CD. The inclusion orientation as evidenced by ROESY measurements involves the inclusion of the 3,4,5-trimethoxybenzyl ring in the CD cavity from the larger rim. This is in agreement with semiempirical molecular modeling calculation. PMID- 22057301 TI - Study on the interaction of sodium morin-5-sulfonate with bovine serum albumin by spectroscopic techniques. AB - In the present investigation, an attempt has been made to study the interaction of sodium morin-5-sulfonate (NaMSA) with the transport proteins, bovine serum albumin (BSA) employing UV-vis, fluorometric and circular dichroism (CD) techniques. The experimental results indicated that the quenching mechanism of BSA by the compound was a static procedure. Various binding parameters were evaluated. The negative value of DeltaH, positive value of DeltaS and the negative value of DeltaG indicated that electrostatic interactions and hydrogen bonding play major roles in the binding of the NaMSA and BSA. Based on the Forster's theory of non-radiation energy transfer, the binding distance, r, between the donor (BSA) and acceptor (NaMSA) was evaluated. The results of CD and UV-vis spectroscopy showed that the binding of this complex to BSA induces some conformational changes in BSA. PMID- 22057302 TI - Radiologic features of NUT midline carcinoma in an adolescent. AB - We present a case of NUT midline carcinoma (NMC) mimicking lymphoma in an adolescent boy, with attention to multidetector CT appearance and pattern of metastasis on [F-18]2-fluoro-2-deoxyglucose positron emission tomography (FDG PET/CT). Few case reports have focused on the imaging characteristics of this rare tumor in the pediatric imaging literature. A newly described but increasingly recognized disease entity, NMC should enter the differential of pediatric midline tumors displaying particularly aggressive characteristics on imaging. PMID- 22057303 TI - An organometallic approach for microporous organic network (MON)-Co3O4 composites: enhanced stability as anode materials for lithium ion batteries. AB - Microporous organic network (MON)-Co(3)O(4) composites were obtained via organometallic complexation of cobalt carbonyl with MONs and showed enhanced stability as anode materials due to the buffering effect of MONs. PMID- 22057304 TI - A graphene nanoribbon network and its biosensing application. AB - Graphene oxide nanoribbons (GONRs) have been prepared by chemically unzipping multiwalled carbon nanotubes (MWCNTs). Thin-film networks of GONRs were fabricated by spray-coating, followed by a chemical or thermal reduction to form reduced graphene oxide nanoribbons (rGONRs). Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) characterizations indicate that the thermal reduction in the presence of ethanol vapor effectively restores the graphitic structure of the GONR as compared to chemical reduction with hydrazine vapor. Electrical measurements under a liquid-gate configuration demonstrates that rGONR network field-effect transistors exhibit much higher on/off ratios than a network of microsized reduced graphene oxides (rGOs) or a continuous film of single layered pristine or chemical vapor deposited (CVD) graphene. Furthermore, we demonstrated the potential applications of rGONR networks for biosensing, specifically, the real-time and sensitive detection of adenosine triphosphate (ATP) molecules. PMID- 22057305 TI - CpG and poly(I:C) stimulation of dendritic cells and fibroblasts limits herpes simplex virus type 1 infection in an IFNbeta-dependent and -independent way. AB - Viral activation of toll-like receptors (TLRs) on dendritic cells (DCs) leads to production of various cytokines, including antiviral type I interferons (IFNs). Synthetic ligands specific for TLRs are also able to induce the production of type I IFNs (IFNalpha/beta) by DCs, suggesting that these ligands have potential as antiviral drugs. In this in vitro study we extensively investigated the antiviral activity of various TLR ligands. Mouse bone marrow (BM) cells were differentiated into plasmacytoid and conventional DCs (pDCs and cDCs), stimulated with various TLR ligands and tested the antiviral abilities of collected supernatants in an in vitro herpes simplex virus type 1 (HSV-1) infection model. We observed a significant IFNbeta-, (but not IFNalpha-) dependent reduction in HSV-1 infection when a mixed pDC/cDC population was stimulated with the TLR9 ligand CpG. In the absence of pDCs, TLR stimulation resulted in less pronounced antiviral effects. The most pronounced antiviral effect was observed when both DC subsets were stimulated with poly(I:C). A similar noticeable antiviral effect was observed when fibroblasts (L929 cells) were stimulated directly with poly(I:C). These poly(I:C)-mediated antiviral effects were only partially IFNbeta-mediated and probably TLR independent. These data demonstrate that TLR ligands are not only able to produce type I IFN but can indeed act as antiviral drugs. In particular poly(I:C), which exerts its antiviral effects even in the absence of DCs, may become a promising drug e.g. to prevent respiratory infections by topical intranasal application. PMID- 22057306 TI - Identification of novel virus inhibitors by influenza A virus specific reporter cell based screening. AB - As influenza viruses have developed resistance towards current drugs, it is urgent to find potential novel antiviral inhibitors. Here we generated an influenza virus reporter cell line in which the luciferase gene was driven by the influenza virus promoter and screened a small compound library (NCI Diversity Set II). Ten compounds were identified to have inhibitory activity against influenza A virus H1N1. Among them, four compounds blocked influenza virus replication through inhibiting the activity of vRNP. The compound NSC 335506 inhibited HA mediated membrane fusion. It showed the inhibitory activity against H1N1, H9N2 and H5N1 subtype but not H3N2. Our results demonstrated that influenza virus reporter cell is a very useful tool to identify novel inhibitors against influenza A virus. PMID- 22057307 TI - Observations of adolescent peer resistance skills following a classroom-based healthy relationship program: a post-intervention comparison. AB - This study examines peer resistance skills following a 21-lesson classroom-based intervention to build healthy relationships and decrease abusive and health-risk behaviors among adolescents. The Fourth R instructs students in positive relationship skills, such as negotiation and delay, for navigating challenging peer and dating scenarios. Observational data from 196 grade 9 students participating in a larger cluster randomized controlled trial were used to evaluate post-intervention acquisition of peer resistance skills. Pairs of students engaged in a role play paradigm with older student actors, where they were subjected to increasing pressure to comply with peer requests related to drugs and alcohol, bullying, and sexual behavior. Specific and global measures of change in peer resistance responses were obtained from two independent sets of observers, blinded to condition. Specific peer resistance responses (negotiation, delay, yielding to pressure, refusal, and compliance) were coded by research assistants; global peer resistance responses were rated by teachers from other schools (thinking / inquiry, application, communication, and perceived efficacy). Students who received the intervention were more likely to demonstrate negotiation skills and less likely to yield to negative pressure relative to controls. Intervention students were also more likely to use delay than controls; control girls were more likely to use refusal responses; the number of times students complied with peer requests did not differ. Teacher ratings demonstrated significant main effects favoring intervention youth on all measures. Program and research implications are highlighted. PMID- 22057308 TI - Risk of falling in Parkinson's disease at the Hoehn-Yahr stage III. AB - BACKGROUND: It is difficult to predict the risk of falling, especially in patients with good motor ability, and the mechanisms underlying the relation between gait patterns and falling in Parkinson's disease (PD) remain unclear. We investigated factors related to falling, including walking speed and time, in patients with Hoehn-Yahr stage III PD. METHODS: We performed clinical assessments and evaluated balance in 30 patients with PD. Information on falling was obtained from questionnaires and personal interviews. Gait patterns were analyzed with the use of an originally designed, suddenly narrowed path. RESULTS: Gait velocity was slower in fallers than in non-fallers (p = 0.047). Unified Parkinson's Disease Rating Scale part II (UPDRS part II) score, fear of falling, and gait velocity were significantly related to falling on analysis with a single logistic model. When a multiple logistic model was used, the UPDRS part II score was significantly related to falling (OR: 1.48, p = 0.037, 95% CI: 1.02-2.16). CONCLUSIONS: Patients with Hoehn-Yahr stage III PD showed slow gait velocity attributed to fear of falling before arrival at a narrowed entrance or while walking on a narrowed path. The UPDRS part II score is significantly related to the risk of future falls. PMID- 22057309 TI - Comparison of the effects of fentanyl, remifentanil, and dexmedetomidine on neuromuscular blockade. AB - PURPOSE: The aim of our study was to compare the effects of fentanyl, remifentanil, and dexmedetomidine on neuromuscular blockade under sevoflurane anesthesia. METHODS: Eighty-four patients were randomized to fentanyl, remifentanil, and dexmedetomidine groups. In the fentanyl group, fentanyl 1.5 MUg/kg was given before induction of anesthesia, and additional 50-MUg boluses were administered. In the remifentanil group, the initial dose of remifentanil 1 MUg/kg was infused in 10 min before induction and 0.1 MUg/kg/min infusion was continued during anesthesia. In the dexmedetomidine group, the initial dose of dexmedetomidine 1 MUg/kg was infused in 10 min before induction and 1 MUg/kg/h infusion was continued during anesthesia. Heart rate, blood pressure, SpO(2), EtCO(2), and TOF (train-of-four) values of all patients were monitored during anesthesia. Times to reach TOF 0 and TOF 25% and intubation quality were recorded. RESULTS: T (0) times and quality of intubation were found to be similar among the groups. T (25) time was found to be significantly longer in the dexmedetomidine group than in the fentanyl and remifentanil groups. CONCLUSION: Dexmedetomidine infusion increased the duration of neuromuscular blockade with vecuronium during general anesthesia. In addition to analgesic and sedative effects, dexmedetomidine may enhance the duration of neuromuscular blockade and may be used as an adjuvant anesthetic during general anesthesia. PMID- 22057310 TI - Generic comparison of protein inference engines. AB - Protein identifications, instead of peptide-spectrum matches, constitute the biologically relevant result of shotgun proteomics studies. How to appropriately infer and report protein identifications has triggered a still ongoing debate. This debate has so far suffered from the lack of appropriate performance measures that allow us to objectively assess protein inference approaches. This study describes an intuitive, generic and yet formal performance measure and demonstrates how it enables experimentalists to select an optimal protein inference strategy for a given collection of fragment ion spectra. We applied the performance measure to systematically explore the benefit of excluding possibly unreliable protein identifications, such as single-hit wonders. Therefore, we defined a family of protein inference engines by extending a simple inference engine by thousands of pruning variants, each excluding a different specified set of possibly unreliable identifications. We benchmarked these protein inference engines on several data sets representing different proteomes and mass spectrometry platforms. Optimally performing inference engines retained all high confidence spectral evidence, without posterior exclusion of any type of protein identifications. Despite the diversity of studied data sets consistently supporting this rule, other data sets might behave differently. In order to ensure maximal reliable proteome coverage for data sets arising in other studies we advocate abstaining from rigid protein inference rules, such as exclusion of single-hit wonders, and instead consider several protein inference approaches and assess these with respect to the presented performance measure in the specific application context. PMID- 22057311 TI - Unusual genomic rearrangements in introns 1 and 22 of the F8 gene. AB - Intron 1 and intron 22 inversions, two large rearrangements of the factor VIII gene, are generally associated with a severe phenotype of haemophilia A and a high risk of inhibitor formation. In several haemophiliacs, diagnostic analyses for detection of these inversions revealed unusual band patterns. Upon further examination, different copy number variations were detected in the factor VIII gene of these patients by multiplex ligation-dependent probe amplification (MLPA). Since these duplications or deletions alone could not sufficiently explain the abnormal band patterns of the first analyses, we assumed a combination of intron 1 or intron 22 inversions together with a copy number variation. RESULT: We could confirm this hypothesis by specific long range PCRs but a detailed characterization of the breakpoints and the mechanisms for these complex rearrangements have yet to be elucidated. PMID- 22057312 TI - Isolated polio-like syndrome after tick-borne encephalitis presenting with acute hyperckemia. AB - Tick borne encephalitis virus infection usually shows a biphasic course. In the first stage of illness symptoms are similar to a flu-like syndrome, then after a defervescence period, fever may represent with neurological manifestations ranging from mild meningitis to severe encephalomyelitis. We report the clinical case of an adult man presented with an acute proximal hyposthenia, severe hyperckemia, clinical and laboratoristic evidence of acute tick borne virus infection. This virus has a favourite tropism for the anterior horn cells of the cervical spine segment. Polio-like syndrome, usually affecting the upper limbs, is the clinical phenotype of an infection of the cervical motoneurons. Usually myelitis is associated to severe encephalitis and a complete diagnosis may be difficult in comatose patients. Rarely, an isolated polio-like syndrome may be the sole neurological complication of tick-borne encephalitis. PMID- 22057313 TI - Laryngeal dystonia in the course of multiple system atrophy: a cause of postoperative respiratory insufficiency. AB - Multiple system atrophy (MSA) is an adult onset, incurable neurodegenerative disease, characterized by symptoms of nervous system failure. Occurrence of laryngeal dystonia indicates increased risk of sudden death caused by airway occlusion. We present the case report of 63-year-old patient with history of orthostatic hypotension, parkinsonism, progressive adynamia, and stridor. The patient was admitted to the hospital for diagnosis of orthostatic hypotension. A diagnosis of possible MSA was made. Because of patient's complaints, an X-ray of the hip joint was taken. It revealed femoral neck fracture. Endoprosthesis insertion under general anesthesia was performed. Two days later the patient presented progressive adynamy and respiratory insufficiency. Endotracheal intubation and respiratory support were required followed by extubation and one more intubation. After second extubation, stridor and acute respiratory insufficiency occurred. Urgent tracheostomy was performed. After 13 days in ICU, the patient was discharged to the rehabilitation center. PMID- 22057314 TI - The role of emergency neurology in Italy: outcome of a consensus meeting for a Intersociety position. AB - A possible definition of clinical, educational and organizing aspects of emergency neurology in Italy is reported in this position paper of Emergency Neurology Intersociety Group, created in 2008 among the two neurological Societies in Italy: Societa Italiana di Neurologia and Societa di Neuroscienze Ospedaliere. The aim of this Group has been the evaluation of the role of neurologist in the emergency setting of Italian hospitals, as well as of the description of different scenarios in which a ward dedicated to a semi-intensive care of neurological emergencies could have a role in the actual organization of academic or general hospitals in our Country. The actual great relevance of neurologist activity in the inpatients treatment, in fact, is actually misleaded as it is the considerable significance of neurological expertise, techniques and support in hospital care pathways also involving neurological manifestations throughout the course of other diseases. Finally, the possible contents of educational programs orienting neurological specialty towards a better comprehension and management of emergency neurological problems either in terms of specific formation or of techniques to be learned by emergency neurologist, are reported as a results of the Consensus Workshop hold in Castiglioncello (LI) in September 12th, 2009. PMID- 22057315 TI - Heatstroke in patients with Parkinson's disease. AB - We present two Parkinson's disease (PD) patients, who experienced heatstroke. Both patients manifested central nervous system dysfunction with elevated core temperature. Despite adequate lowering of the body temperature, multiorgan dysfunction syndrome including encephalopathy, rhabdomyolysis, acute renal failure, acute respiratory failure, and disseminated intravascular coagulopathy was noted in one patient, leading to permanent neurologic damage. Because the ensuing multiorgan dysfunction could determine the functional prognosis in heatstroke patients, it is important to provide information about the prevention of heatstroke to patients, who are isolated or are severely disabled in the advanced stages of PD. PMID- 22057316 TI - Crystal structure of HydF scaffold protein provides insights into [FeFe] hydrogenase maturation. AB - [FeFe]-hydrogenases catalyze the reversible production of H2 in some bacteria and unicellular eukaryotes. These enzymes require ancillary proteins to assemble the unique active site H-cluster, a complex structure composed of a 2Fe center bridged to a [4Fe-4S] cubane. The first crystal structure of a key factor in the maturation process, HydF, has been determined at 3 A resolution. The protein monomer present in the asymmetric unit of the crystal comprises three domains: a GTP-binding domain, a dimerization domain, and a metal cluster-binding domain, all characterized by similar folding motifs. Two monomers dimerize, giving rise to a stable dimer, held together mainly by the formation of a continuous beta sheet comprising eight beta-strands from two monomers. Moreover, in the structure presented, two dimers aggregate to form a supramolecular organization that represents an inactivated form of the HydF maturase. The crystal structure of the latter furnishes several clues about the events necessary for cluster generation/transfer and provides an excellent model to begin elucidating the structure/function of HydF in [FeFe]-hydrogenase maturation. PMID- 22057317 TI - PEDF effectively decreases VEGF to PEDF messenger RNA ratio of the inner edge of rat hepatocellular carcinoma induced by diethyl nitrosamine - an "in vivo" study. AB - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is hypervascular. Pigment epithelial derived factor (PEDF), a potent angiogenic inhibitor, usually coexists with the stimulator, vascular endothelial growth factor (VEGF). To assess the treatment effect of PEDF on growing HCCs we conducted this study. METHODOLOGY: Pathogen-free male LEW/SsN rats (n=150 in 5 groups), group A as control, groups B, C, D and E were given diethyl nitrosamine (DEN) to induce HCC. Group C received intraperitoneal injection (i.p.) of PEDF (0.3mg/kg/day) since induction. Group D received i.p. of PEDF (0.3mg/kg/day) since 18th week (wk). Group E received i.p. of normal saline. We examined VEGF mRNA and PEDF mRNA of livers of group A and 3 different areas (advancing edge, inner edge and central area) of HCC of other 4 groups at 24th wk. RESULTS: Tumor weight and metastasis score of group C were significantly lower (p=0.026). Comparing among 5 groups, the ratio of VEGF/PEDF mRNA of inner edge of HCC of group C and D were significantly lower (p=0.002 and p=0.011). By multivariate analysis, the difference of group C remains significant (p=0.030). CONCLUSIONS: PEDF significantly suppresses rat hepatocarcinogenesis if given simultaneously since cancer induction. The significant decrease of VEGF/PEDF mRNA is at the inner edge of HCC. PMID- 22057318 TI - Gastric motility and emptying in cirrhotic patients with portal hypersensitive gastropathy. AB - BACKGROUND/AIMS: Our aim was to clarify gastric motility and emptying in LC patients with PHG. METHODOLOGY: A total of 30 LC patients (18 with mild gastropathy type, 12 with severe gastropathy type) with a mean age with 65.8 yr were enrolled and 17 healthy participants were recruited as the control group. Electrogastrography was performed to examine gastric motility in the fasting, nocturnal and 2 hr postprandial phase. Subsequently, patients with LC and control were performed to measure gastric emptying of solids with the breath test using 13C for labeling the octanoic acid. Breath samples were obtained every 15 to 30 minutes for 5 hours. RESULTS: The mean frequency of the EGG while fasting with severe PHG was significantly increased compared to mild PHG (p<0.05). The mean frequency of the EGG at 1-hr and 2-hr postprandially with severe PHG was significantly increased compared to mild PHG. The half time of GE with both mild and severe PHG was significantly increased compared to controls. CONCLUSIONS: Postprandial EGG and GE in LC patients would be affected by PHG. PMID- 22057319 TI - Release of extracellular purines from plant roots and effect on ion fluxes. AB - Extracellular purine nucleotides appear capable of regulating plant development, defence and stress responses by acting in part as agonists of plasma membrane calcium channels. Factors stimulating ATP release include wounding, osmotic stress and elicitors. Here we show that exogenous abscisic acid and L-glutamate can also cause ATP accumulation around Arabidopsis thaliana roots. Release of ADP from root epidermis would trigger ionotropic receptor-like activity in the plasma membrane, resulting in transient elevation of cytosolic free calcium. Root epidermal protoplasts (expressing aequorin as a cytosolic free calcium reporter) can support an extracellular ADP-induced cytosolic calcium elevation in the presence of an extracellular reductant. This confirms that ADP could elicit calcium-based responses distinct to those of ATP, which have been shown previously to involve production of extracellular reactive oxygen species. PMID- 22057320 TI - Emerging aspects of ER organization in root hair tip growth: lessons from RHD3 and Atlastin. AB - Cell polarity is a fundamental aspect of eukaryotic cells. A central question for cell biologists is how the polarity of a cell is established and maintained. Root hairs are exceptionally polarized structures formed from specific root epidermal cells. The morphogenesis of root hairs is characterized by the localized cell growth in a small dome at the tip of the hair, a process called tip growth. Root hairs are thus an attractive model system to study the establishment and maintenance of cell polarity in eukaryotes. Research on Arabidopsis root hairs has identified a plethora of molecular and cellular components that are important for root hair tip growth. Recently, studies on RHD3 and Atlastin have revealed a surprising similarity with respect to the role of the tubular ER network in tip growth of root hairs in plants and the axonal outgrowth of corticospinal neurons in neurological disorders known as hereditary spastic paraplegia (HSP). In this mini-review, we highlight recent progress in understanding of the function and regulation of RHD3 in the generation of the tubular ER network and discussed ways in which RHD3 could be involved in the establishment and maintenance of root hair tip growth. PMID- 22057321 TI - Does brassinosteroid function require chromatin remodeling? AB - The phytohormone brassinosteroid (BR) is crucial for plant growth and development. Although genetic and molecular approaches have improved understanding of the cellular BR signaling pathway, we still do not have sufficient knowledge about the function of BR. Therefore, proteomic analysis was used to elucidate BR signaling and gene expression in the nuclei of suspended Arabidopsis cells treated with brassinolide, a bioactive BR, or brassinazole, a BR biosynthesis inhibitor. Interestingly, chromatin remodeling-related proteins, the abundance of which was altered in response to cellular BR levels, were identified. This suggested that BR-induced gene expression is regulated not only by transcription factors directly binding to cis-elements, but also by chromatin remodeling in response to BR signaling. In this addendum, we summarize the functions of our identified nuclear proteins in chromatin remodeling and discuss the need for chromatin remodeling regulated by BR signal transduction for expression of BR-induced genes. PMID- 22057322 TI - Roles of EDR1 in non-host resistance of Arabidopsis. AB - Entry control of Arabidopsis thaliana against non-adapted powdery mildews largely depends on the PEN1 secretion pathway and the PEN2-PEN3 antifungal metabolite pathway, and is critical for non-host resistance. In a recent study, we reported that ENHANCED DISEASE RESISTANCE 1 (EDR1) plays a role in entry control against a non-adapted anthracnose fungus, which exhibits an infection style distinct from that of powdery mildews. Results obtained using edr1 pen2 double mutants indicate that the contribution of EDR1 to non-host resistance is independent of that of the PEN2-mediated defence pathway. Comparative transcript profiling revealed that EDR1 is critical for expression of four plant defensin genes. The MYC2-encoded transcription factor represses defensin expression. Inactivation of MYC fully restored defensin expression in edr1 mutants, implying that EDR1 cancels MYC2 function to regulate defensin expression. These findings indicate that EDR1 exerts a critical role in non-host resistance, in part by inducing antifungal peptide expression via interference in MYC2-mediated repressor function. PMID- 22057323 TI - Potential but limited redundant roles of MtPIN4, MtPIN5 and MtPIN10/SLM1 in the development of Medicago truncatula. AB - Auxin polar transport is crucial in regulating plant growth and patterning. As auxin efflux carriers, the PIN FORMED (PIN) proteins are responsible for transportation of auxin out of the cell. There are eight and ten PIN members in Arabidopsis (AtPIN) and Medicago truncatula (MtPIN), respectively. Compared with MtPIN10/SMOOTH LEAF MARGIN1 (SLM1), MtPIN4 exhibits a closer relationship with AtPIN1 based phylogenetic analysis. In addition, the gene structure and distribution of transmembrane segments of MtPIN4, MtPIN5 and MtPIN10/SLM1 are similar, implying possible redundant roles among them. However, analysis using Gene Expression Atlas revealed different expression patterns among MtPIN4, MtPIN5 and MtPIN10/SLM1. Loss of function of MtPIN10/SLM1 in M. truncatula resulted in pleiotropic phenotypes in different organs, which are similar with the defects in the pin1 mutant of Arabidopsis, suggesting that the MtPIN10/SLM1 is a putative ortholog of AtPIN1. MtPIN4, MtPIN5 and MtPIN10/SLM1 may have limited redundant functions in the development of M. truncatula. The creation of double and triple mutants will help to elucidate their potential roles in auxin transport and plant development. PMID- 22057324 TI - Bisymmetry in the embryonic root is dependent on cotyledon number and position. AB - In the shoot pole of Arabidopsis embryos, radial symmetry is broken by cotyledon specification. Subsequently, the radial pattern of the embryo axis is converted to bisymmetric. In a recent publication, we showed that distinct boundaries of hormonal signalling output specify the vascular pattern in the root meristem through a mutually inhibitory feedback loop between the hormones auxin and cytokinin. We observed that during embryogenesis, symmetry breakage in the root pole coincided with an influx of auxin from the cotyledons. In this manuscript, we provide genetic data to support the role of the cotyledons in initiating symmetry breaking in the embryonic root pole. Mutants with alterations in cotyledon number fail to establish bisymmetry in the embryo axis. These data further support the idea that input from the cotyledons may be required for the propagation of bisymmetry from the cotyledons to the embryonic root. PMID- 22057325 TI - Plant lipid bodies and cell-cell signaling: a new role for an old organelle? AB - Plant lipid droplets are found in seeds and in post-embryonic tissues. Lipid droplets in seeds have been intensively studied, but those in post-embryonic tissues are less well characterised. Although known by a variety of names, here we will refer to all of them as lipid bodies (LBs). LBs are unique spherical organelles which bud off from the endoplasmic reticulum, and are composed of a single phospholipid (PL) layer enclosing a core of triacylglycerides. The PL monolayer is coated with oleosin, a structural protein that stabilizes the LB, restricts its size, and prevents fusion with adjacent LBs. Oleosin is uniquely present at LBs and is regarded as a LB marker. Although initially viewed as simple stores for energy and carbon, the emerging view is that LBs also function in cytoplasmic signalling, with the minor LB proteins caleosin and steroleosin in a prominent role. Apart from seeds, a variety of vegetative and floral structures contain LBs. Recently, it was found that numerous LBs emerge in the shoot apex of perennial plants during seasonal growth arrest and bud formation. They appear to function in dormancy release by reconstituting cell-cell signalling paths in the apex. As apices and orthodox seeds proceed through comparable cycles of dormancy and dehydration, the question arises to what degree LBs in apices share functions with those in seeds. We here review what is known about LBs, particularly in seeds, and speculate about possible unique functions of LBs in post-embryonic tissues in general and in apices in particular. PMID- 22057326 TI - Does polyamine catabolism influence root development and xylem differentiation under stress conditions? AB - Amine oxidases (AOs) oxidize polyamines (PAs) to aldehydes, simultaneously producing the removed amine moiety and hydrogen peroxide (H2O2). AOs, which include copper-containing amine oxidases (CuAOs) and flavin-containing amine oxidases (PAOs), are stress-inducible enzymes involved in both PA homeostasis and H2O2 production. Here, we suggest that H2O2 derived from PAO-mediated PA catabolism has a role in inducing root xylem differentiation during plant stress responses, whereas its involvement in this event during plant development under physiological conditions is not suitably supported by the currently available data. Moreover, we show that spermidine (Spd) supply leads to a higher induction of cell death in wild-type (WT) tobacco (Nicotiana tabacum) plants as compared to tobacco plants over-expressing maize (Zea mays) PAO (S-ZmPAO) in the cell wall, in apparent contradiction with the already reported results obtained by the analysis of the corresponding WT and S-ZmPAO Spd-untreated plants. Considering this last observation, we propose that PAs diversely affect plant development and stress responses depending on the expression levels of AOs, which in turn may lead to different plant responses by altering the PAs/H2O2 balance. PMID- 22057327 TI - Is GC bias in the nuclear genome of the carnivorous plant Utricularia driven by ROS-based mutation and biased gene conversion? AB - At less than 90 Mbp, the tiny nuclear genome of the carnivorous bladderwort plant Utricularia is an attractive model system for studying molecular evolutionary processes leading to genome miniaturization. Recently, we reported that expression of genes encoding DNA repair and reactive oxygen species (ROS) detoxification enzymes is highest in Utricularia traps, and we argued that ROS mutagenic action correlates with the high nucleotide substitution rates observed in the Utricularia plastid, mitochondrial, and nuclear genomes. Here, we extend our analysis of 100 nuclear genes from Utricularia and related asterid eudicots to examine nucleotide substitution biases and their potential correlation with ROS-induced DNA lesions. We discovered an unusual bias toward GC nucleotides, most prominently in transition substitutions at the third position of codons, which are presumably silent with respect to adaptation. Given the general tendency of biased gene conversion to drive GC bias, and of ROS to induce double strand breaks requiring recombinational repair, we propose that some of the unusual features of the bladderwort and its genome may be more reflective of these nonadaptive processes than of natural selection. PMID- 22057328 TI - Plant TOR signaling components. AB - Cell growth is a process that needs to be tightly regulated. Cells must be able to sense environmental factors like nutrient abundance, the energy level or stress signals and coordinate growth accordingly. The Target Of Rapamycin (TOR) pathway is a major controller of growth-related processes in all eukaryotes. If environmental conditions are favorable, the TOR pathway promotes cell and organ growth and restrains catabolic processes like autophagy. Rapamycin is a specific inhibitor of the TOR kinase and acts as a potent inhibitor of TOR signaling. As a consequence, interfering with TOR signaling has a strong impact on plant development. This review summarizes the progress in the understanding of the biological significance and the functional analysis of the TOR pathway in plants. PMID- 22057329 TI - Role of salicylic acid in induction of plant defense system in chickpea (Cicer arietinum L.). AB - Salicylic acid (SA), a plant hormone plays an important role in induction of plant defense against a variety of biotic and abiotic stresses through morphological, physiological and biochemical mechanisms. A series of experiments were carried out to evaluate the biochemical response of the chickpea (Cicer arietinum L.) plants to a range of SA concentrations (1, 1.5, and 2 mM). Water treated plants were maintained as control. Activities of peroxidase (POD) and polyphenol oxidase (PPO) were evaluated and amounts of total phenols, hydrogen peroxide (H2O2), and proteins were calculated after 96 h of treatment. Plants responded very quickly to SA at 1.5 mM and showed higher induction of POD and PPO activities, besides the higher accumulation of phenols, H2O2 and proteins. Plants treated with SA at 2 mM showed phytotoxic symptoms. These results suggest that SA at 1.5 mM is safe to these plants and could be utilized for the induction of plant defense. PMID- 22057330 TI - Cellulose synthesis in two secondary cell wall processes in a single cell type. AB - Plant cells have a rigid cell wall that constrains internal turgor pressure yet extends in a regulated and organized manner to allow the cell to acquire shape. The primary load-bearing macromolecule of a plant cell wall is cellulose, which forms crystalline microfibrils that are organized with respect to a cell's function and shape requirements. A primary cell wall is deposited during expansion whereas secondary cell wall is synthesized post expansion during differentiation. A complex form of asymmetrical cellular differentiation occurs in Arabidopsis seed coat epidermal cells, where we have recently shown that two secondary cell wall processes occur that utilize different cellulose synthase (CESA) proteins. One process is to produce pectinaceous mucilage that expands upon hydration and the other is a radial wall thickening that reinforced the epidermal cell structure. Our data illustrate polarized specialization of CESA5 in facilitating mucilage attachment to the parent seed and CESA2, CESA5 and CESA9 in radial cell wall thickening and formation of the columella. Herein, we present a model for the complexity of cellulose biosynthesis in this highly differentiated cell type with further evidence supporting each cellulosic secondary cell wall process. PMID- 22057331 TI - Plant responses to water stress: role of reactive oxygen species. AB - Responses of plants to water stress may be assigned as either injurious change or tolerance index. One of the primary and cardinal changes in response to drought stress is the generation of reactive oxygen species (ROS), which is being considered as the cause of cellular damage. However, recently a signaling role of such ROS in triggering the ROS scavenging system that may confer protection or tolerance against stress is emerging. Such scavenging system consists of antioxidant enzymes like SOD, catalase and peroxidases, and antioxidant compounds like ascorbate, reduced glutathione; a balance between ROS generation and scavenging ultimately determines the oxidative load. As revealed in case of defence against pathogen, signaling via ROS is initiated by NADPH oxidase catalyzed superoxide generation in the apoplastic space (cell wall) followed by conversion to hydrogen peroxide by the activity of cell wall-localized SOD. Wall peroxidase may also play role in ROS generation for signaling. Hydrogen peroxide may use Ca2+ and MAPK pathway as downstream signaling cascade. Plant hormones associated with stress responses like ABA and ethylene play their role possibly via a cross talk with ROS towards stress tolerance, thus projecting a dual role of ROS under drought stress. PMID- 22057332 TI - ARF-GTPase activating protein mediates auxin influx carrier AUX1 early endosome trafficking to regulate auxin dependent plant development. AB - Polar auxin transport (PAT) plays a critical role in the regulation of plant growth and development. Auxin influx carrier AUX1 is predominantly localized to the upper side of specific root cells in Arabidopsis. Overexpression of OsAGAP, an ARF-GTPase activating protein in rice, could induce the accumulation of AUX1. But the mechanism is poorly known. Here we reported that over-expression of ARF GAP could reduce the thickness and bundling of microfilament (MF) which possibly could greatly interfere with the endocytosis of AUX1 early endosome; but not the exocytosis of AUX1 recycling endosome. Therefore, AFR-GAP over-expression suppressed-MF bundling is likely involved in regulating endocytosis of Auxin influx carrier AUX1 and in mediating auxin dependent plant development. PMID- 22057333 TI - The reciprocal regulation of abscisic acid and ethylene biosyntheses. AB - Ethylene and abscisic acid (ABA) have compact effects on plant development and stress responses. It is not well understood about the mechanism of ABA modulation in ethylene biosynthesis. In our recent research, HY5-AtERF11 regulon was evidenced to connect the ABA action and ethylene biosynthesis. In this paper, by analyzing the expression of ABA biosynthesis genes and the ABA concentration in ethylene over-production mutants, we demonstrated that ethylene production affected by HY5-AtERF11 regulon targeted gene increased the expression of ABA biosynthesis genes and its contents. In addition, we discussed that HY5 might function as a convergence point of multiple hormones in response to light. PMID- 22057334 TI - Control of dicot leaf blade expansion by a WOX gene, STF. AB - WUSCHEL-RELATED HOMEOBOX (WOX) genes are plant specific transcription factors that serve as master switches controlling key developmental programs from embryo apical-basal asymmetric patterning to organizing stem cells and development of lateral organs. Recently, we reported the requirement of a WOX1/MAW-like gene, STENOFOLIA (STF), for blade outgrowth and leaf vascular patterning in Medicago truncatula and Nicotiana sylvestris. The stf mutant in Medicago produces narrow leaves where mediolateral outgrowth of the blade is severely curtailed while proximodistal growth and trifoliate identity remain unaffected. The lam1 mutant in N. sylvestris produces leaves devoid of blade tissue with just 1-2 layers of rudimentary strips and lacks stem elongation. stf and lam1 mutants have narrow petals and are female sterile due to defective ovule development. Morphological analysis of mutants and STF expression patterns suggest that STF regulates blade outgrowth mainly by controlling cell division in the margins of leaf primordium. Both the blade and flower phenotypes of lam1 can be complemented with WUS expressed under the STF promoter suggesting a conserved mechanism in stem cell maintenance and lateral organ development. PMID- 22057335 TI - Phototropin-dependent biased relocalization of cp-actin filaments can be induced even when chloroplast movement is inhibited. AB - In a recent publication using an actin-visualized line of Arabidopsis (Ichikawa et al. 2011, ref. 11), we reported a detailed analysis with higher time resolution on the dynamics of chloroplast actin filaments (cp-actin filaments) during chloroplast avoidance movement and demonstrated a good correlation between the biased configuration of cp-actin filaments and chloroplast movement. However, we could not conclusively determine whether the reorganization of cp-actin filaments into a biased configuration preceded actual chloroplast movement (and, thus, whether it could be a cause of the movement). In this report, we present clear evidence that the reorganization of cp-actin filaments into a biased distribution is induced even in the absence of the actual movement of chloroplasts. When the cells were treated with 2,3-butanedione monoxime (BDM), a potent inhibitor of myosin ATPase, chloroplast motility was completely suppressed. Nevertheless, the disappearance and biased relocalization of cp-actin filaments toward the side of the prospective movement direction were induced by irradiation with a strong blue light microbeam. The results definitively indicate that the reorganization of cp-actin filaments is not an effect of chloroplast movement; however, it is feasible that the biased localization of cp-actin filaments is an event leading to chloroplast movement. PMID- 22057336 TI - Modulation of root branching by a coumarin derivative. AB - A healthy root system is crucial to plant growth and survival. To maintain efficiency of root function, plants have to dynamically modulate root system architecture through various adaptive mechanisms such as lateral root formation to respond to a changing and diversified soil environment. Exogenous application of a coumarin derivative, 4-methylumbelliferone (4-MU), in Arabidopsis thaliana inhibits seed germination by mainly reducing primary root growth. UDP glycosyltransferases play an integral role in the biochemical mechanism of 4-MU detoxification in plant roots.1 However, 4-MU treatment also dramatically led to increased lateral root initiation, elongation and density. Moreover, marked root bending at the root-hypocotyl junction and auxin redistribution appeared to contribute to the 4-MU-mediated lateral root formation. We propose that 4-MU would serve as a useful chemical tool to study auxin-mediated root branching. PMID- 22057337 TI - sn-Glycerol-3-phosphate acyltransferases in plants. AB - sn-Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the acylation at sn-1 position of glycerol-3-phosphate to produce lysophosphatidic acid (LPA). LPA is an important intermediate for the formation of different types of acyl-lipids, such as extracellular lipid polyesters, storage and membrane lipids. Three types of GPAT have been found in plants, localizing to the plastid, endoplasmic reticulum, and mitochondria. These GPATs are involved in several lipid biosynthetic pathways and play important biological roles in plant development. In the present review, we will focus on the recent progress in studying the physiological functions of GPATs and their metabolic roles in glycerolipid biosynthesis. PMID- 22057338 TI - Glycinebetaine and abiotic stress tolerance in plants. AB - The accumulation of osmolytes like glycinebetaine (GB) in cell is known to protect organisms against abiotic stresses via osmoregulation or osmoprotection. Transgenic plants engineered to produce GB accumulate very low concentration of GB, which might not be sufficient for osmoregulation. Therefore, other roles of GB like cellular macromolecule protection and ROS detoxification have been suggested as mechanisms responsible for abiotic stress tolerance in transgenic plants. In addition, GB influences expression of several endogenous genes in transgenic plants. The new insights gained about the mechanism of stress tolerance in GB accumulating transgenic plants are discussed. PMID- 22057339 TI - How are tonoplast proteins degraded? AB - Protein turnover is fundamental both for development and cellular homeostasis. The mechanisms responsible for the turnover of integral membrane proteins in plant cells are however still largely unknown. Recently, considerable attention has been devoted to the degradation of plasma membrane proteins. We have now studied the turnover of a tonoplast protein, the potassium channel TPK1, in fully differentiated Arabidopsis leaf cells and showed that its degradation occurs upon internalization into the vacuole. Here, we discuss the possible mechanisms and triggering events involved. PMID- 22057340 TI - Pyrosequencing data reveals tissue-specific expression of lineage-specific transcripts in chickpea. AB - Chickpea is a very important crop legume plant, which provides a protein-rich supplement to cereal-based diets and has the ability to fix atmospheric nitrogen. Despite its economic importance, the functional genomic resources for chickpea are very limited. Recently, we reported the complete transcriptome of chickpea using next generation sequencing technologies. We analyzed the tissue-specific expression of chickpea transcripts based on RNA-seq data. In addition, we identified two sets of lineage-specific genes, including a total of 3,632 chickpea-specific and 741 as legume-specific transcripts based on sequence comparison with other species within plant kingdom. The study of lineage-specific genes provides insights into the species-/lineage-specific functions and evolutionary processes. In this study, we further analyze the expression profiles of legume- and chickpea-specific transcripts in various tissue samples. Several legume- and chickpea-specific transcripts showed preferential and/or specific expression in the tissue samples analyzed. Our analysis provides evidence for the role of legume- and chickpea-specific transcripts in various tissues and opens an important area of future research to elucidate the exact role of these genes. PMID- 22057341 TI - Comparative analysis of protein transport in the N. benthamiana vasculature reveals different destinations. AB - We investigated the vascular transport of exogenously applied proteins and compared their delivery to various aerial parts of the plant with carboxy fluorescein dye. Alexafluor tagged bovine serum albumin (Alexa-BSA) moves at a low level to upper parts of the plant and unloads to the apoplast. Alexafluor tagged Histone H1 (Alexa-Histone) moves rapidly throughout the plant and is retained in the phloem and phloem parenchyma. Both Alexa-Histone and -BSA were exported from leaf veins class II and III but they unloaded completely into the leaf lamina with barely any residual fluorescence left inside the leaf veins. Fluorescein tagged hepatitis C virus core protein (fluorescein-HCV) moves more rapidly than BSA through the plant and was restricted to the leaf veins. Fluorescein-HCV failed to unload to the leaf lamina. These combined data suggest that there is not a single default pathway for the transfer of exogenous proteins through the plant. Specific protein properties appear to determine their destination and transport properties within the phloem. PMID- 22057342 TI - Arabidopsis Pht1;5 plays an integral role in phosphate homeostasis. AB - The mobilization of inorganic phosphate (Pi) in planta is a complex process regulated by a number of developmental and environmental cues. Plants possess many Pi transporters that acquire Pi from the rhizosphere and translocate it throughout the plant. A few members of the high-affinity Pht1 family of Pi transporters have been functionally characterized and, for the most part, have been shown to be involved in Pi acquisition. We recently demonstrated that the Arabidopsis Pi transporter, Pht1;5, plays a key role in translocating Pi between tissues. Loss-of-function pht1;5 mutant seedlings accumulated more P in shoots relative to wild type but less in roots. In contrast, overexpression of Pht1;5 resulted in a lower P shoot:root ratio compared with wild type. Also, the rosette leaves of Pht1;5-overexpression plants senesced early and contained less P, whereas reproductive organs accumulated more P than those of wild type. Herein we report the molecular response of disrupting Pht1;5 expression on other factors known to modulate P distribution. The results reveal reciprocal mis-regulation of PHO1, miR399d, and At4 in the pht1;5 mutant and Pht1;5-overexpressor, consistent with the corresponding changes in P distribution in these lines. Together our studies reveal a complex role for Pht1;5 in regulating Pi homeostasis. PMID- 22057343 TI - Sample selection, preparation methods, and the apparent tensile properties of silkworm (B. mori) cocoon silk. AB - Reported literature values of the tensile properties of natural silk cover a wide range. While much of this inconsistency is the result of variability that is intrinsic to silk, some is also a consequence of differences in the way that silk is prepared for tensile tests. Here we explore how measured mechanical properties of Bombyx mori cocoon silk are affected by two intrinsic factors (the location from which the silk is collected within the cocoon, and the color of the silk), and two extrinsic factors (the storage conditions prior to testing, and different styles of reeling the fiber). We find that extrinsic and therefore controllable factors can affect the properties more than the intrinsic ones studied. Our results suggest that enhanced inter-laboratory collaborations, that lead to standardized sample collection, handling, and storage protocols prior to mechanical testing, would help to decrease unnecessary (and complicating) variation in reported tensile properties. PMID- 22057344 TI - ECIRS (Endoscopic Combined Intrarenal Surgery) in the Galdakao-modified supine Valdivia position: a new life for percutaneous surgery? AB - BACKGROUND: Percutaneous nephrolithotomy (PNL) is still the gold-standard treatment for large and/or complex renal stones. Evolution in the endoscopic instrumentation and innovation in the surgical skills improved its success rate and reduced perioperative morbidity. ECIRS (Endoscopic Combined IntraRenal Surgery) is a new way of affording PNL in a modified supine position, approaching antero-retrogradely to the renal cavities, and exploiting the full array of endourologic equipment. ECIRS summarizes the main issues recently debated about PNL. METHODS: The recent literature regarding supine PNL and ECIRS has been reviewed, namely about patient positioning, synergy between operators, procedures, instrumentation, accessories and diagnostic tools, step-by-step standardization along with versatility of the surgical sequence, minimization of radiation exposure, broadening to particular and/or complex patients, limitation of post-operative renal damage. RESULTS: Supine PNL and ECIRS are not superior to prone PNL in terms of urological results, but guarantee undeniable anesthesiological and management advantages for both patient and operators. In particular, ECIRS requires from the surgeon a permanent mental attitude to synergy, standardized surgical steps, versatility and adherence to the ongoing clinical requirements. ECIRS can be performed also in particular cases, irrespective to age or body habitus. The use of flexible endoscopes during ECIRS contributes to minimizing radiation exposure, hemorrhagic risk and post-PNL renal damage. CONCLUSIONS: ECIRS may be considered an evolution of the PNL procedure. Its proposal has the merit of having triggered the critical analysis of the various PNL steps and of patient positioning, and of having transformed the old static PNL into an updated approach. PMID- 22057345 TI - Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo. AB - Advancing understanding of human coronary artery disease requires new methods that can be used in patients for studying atherosclerotic plaque microstructure in relation to the molecular mechanisms that underlie its initiation, progression and clinical complications, including myocardial infarction and sudden cardiac death. Here we report a dual-modality intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo using a combination of optical frequency domain imaging (OFDI) and near-infrared fluorescence (NIRF) imaging. By providing simultaneous molecular information in the context of the surrounding tissue microstructure, this new catheter could provide new opportunities for investigating coronary atherosclerosis and stent healing and for identifying high risk biological and structural coronary arterial plaques in vivo. PMID- 22057346 TI - Identification of a central role for complement in osteoarthritis. AB - Osteoarthritis, characterized by the breakdown of articular cartilage in synovial joints, has long been viewed as the result of 'wear and tear'. Although low-grade inflammation is detected in osteoarthritis, its role is unclear. Here we identify a central role for the inflammatory complement system in the pathogenesis of osteoarthritis. Through proteomic and transcriptomic analyses of synovial fluids and membranes from individuals with osteoarthritis, we find that expression and activation of complement is abnormally high in human osteoarthritic joints. Using mice genetically deficient in complement component 5 (C5), C6 or the complement regulatory protein CD59a, we show that complement, specifically, the membrane attack complex (MAC)-mediated arm of complement, is crucial to the development of arthritis in three different mouse models of osteoarthritis. Pharmacological modulation of complement in wild-type mice confirmed the results obtained with genetically deficient mice. Expression of inflammatory and degradative molecules was lower in chondrocytes from destabilized joints from C5-deficient mice than C5 sufficient mice, and MAC induced production of these molecules in cultured chondrocytes. Further, MAC colocalized with matrix metalloprotease 13 (MMP13) and with activated extracellular signal-regulated kinase (ERK) around chondrocytes in human osteoarthritic cartilage. Our findings indicate that dysregulation of complement in synovial joints has a key role in the pathogenesis of osteoarthritis. PMID- 22057347 TI - Inhibition of proteasome deubiquitinating activity as a new cancer therapy. AB - Ubiquitin-tagged substrates are degraded by the 26S proteasome, which is a multisubunit complex comprising a proteolytic 20S core particle capped by 19S regulatory particles. The approval of bortezomib for the treatment of multiple myeloma validated the 20S core particle as an anticancer drug target. Here we describe the small molecule b-AP15 as a previously unidentified class of proteasome inhibitor that abrogates the deubiquitinating activity of the 19S regulatory particle. b-AP15 inhibited the activity of two 19S regulatory-particle associated deubiquitinases, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b-AP15 induced tumor cell apoptosis that was insensitive to TP53 status and overexpression of the apoptosis inhibitor BCL2. We show that treatment with b-AP15 inhibited tumor progression in four different in vivo solid tumor models and inhibited organ infiltration in an acute myeloid leukemia model. Our results show that the deubiquitinating activity of the 19S regulatory particle is a new anticancer drug target. PMID- 22057348 TI - Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. AB - Three major modes of cancer therapy (surgery, radiation and chemotherapy) are the mainstay of modern oncologic therapy. To minimize the side effects of these therapies, molecular-targeted cancer therapies, including armed antibody therapy, have been developed with limited success. In this study, we have developed a new type of molecular-targeted cancer therapy, photoimmunotherapy (PIT), that uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, conjugated to monoclonal antibodies (mAbs) targeting epidermal growth factor receptors. Cell death was induced immediately after irradiating mAb-IR700 bound target cells with NIR light. We observed in vivo tumor shrinkage after irradiation with NIR light in target cells expressing the epidermal growth factor receptor. The mAb-IR700 conjugates were most effective when bound to the cell membrane and produced no phototoxicity when not bound, suggesting a different mechanism for PIT as compared to conventional photodynamic therapies. Target selective PIT enables treatment of cancer based on mAb binding to the cell membrane. PMID- 22057349 TI - Glu-108 is essential for subunit assembly and dimer stability of D phosphoglycerate dehydrogenase from Entamoeba histolytica. AB - D-phosphoglycerate dehydrogenase catalyses the first step of phosphorylated serine biosynthesis pathway by oxidizing 3-phosphoglycerate, a glycolysis intermediate into phosphohydroxsy pyruvate. For Entamoeba histolytica this pathway is an integral part of the cysteine metabolism, which is considered to be vital for growth and survival of the parasite. Entamoeba histolytica D phosphoglycerate dehydrogenase (EhPGDH) exists as a homodimer at pH 7. Mild acidic conditions induce significant changes in the functional and structural features of the protein as observed by enzymatic activity, spectropolarimetric measurements and fluorescence spectroscopy. Most interestingly the oligomeric status of the protein was lost and a functionally inactive monomer was stabilized at pH 5. Computational modeling and molecular dynamic simulations show that dimeric assembly of EhPGDH was stabilized with the help of several inter-subunit non-covalent interactions and subunit dissociation at pH 5 can be attributed to protonation of acidic amino acid residues present at the dimer interface. Site directed mutagenesis studies suggest that Glu-108 is essential for subunit assembly as the E108A mutant existed as monomer even at pH 7. The studies unequivocally show that the electrostatic interactions at the dimer interface play a crucial role in the stability of the protein and a complete dimer is essentially required for optimal enzymatic activity. PMID- 22057350 TI - Characterization of acyl carrier protein and LytB in Babesia bovis apicoplast. AB - The apicoplast is a highly specialized organelle that mediates required functions in the growth and replication of apicomplexan parasites. Despite structural conservation of the apicoplast among different parasite genera and species, there are also critical differences in the metabolic requirements of different parasites and at different stages of the life cycle. To specifically compare apicoplast pathways between parasites that have both common and unique stages, we characterized the apicoplast in Babesia bovis, which has only intraerythrocytic asexual stages in the mammalian host, and compared it to that of Plasmodium falciparum, which has both asexual intraerythrocytic and hepatic stages. Specifically focusing on the type II fatty acid (FASII) and isoprenoid (MEP) biosynthesis pathways, we searched for pathway components and retention of active sites within the genome, localized key components [acyl carrier protein (ACP) and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB)] to the apicoplast, and demonstrated that the N-terminal bipartite signals of both proteins are required and sufficient for trafficking to the apicoplast lumen. Using specific pharmacologic inhibition, we demonstrated that MEP biosynthesis may be disrupted and its presence is required for intraerythrocytic growth of B. bovis asexual stages, consistent with the genomic pathway analysis and with its requirement in the asexual erythrocytic stages of P. falciparum. In contrast, FASII biosynthesis may or may not be present and specific drug targets did not have any inhibitory effect to B. bovis intraerythrocytic growth, which is consistent with the lack of requirement for P. falciparum intraerythrocytic growth. However, genomic analysis revealed the loss of FASII pathway components in B. bovis whereas the pathway is intact for P. falciparum but regulated to be expressed when needed (hepatic stages) and silent when not (intraerythrocytic stages). The results indicate specialized molding of apicoplast biosynthetic pathways to meet the requirements of individual apicomplexan parasites and their unique intracellular niches. PMID- 22057351 TI - Mid-term clinical results of alumina medial pivot total knee arthroplasty. AB - PURPOSE: The medial pivot total knee prosthesis has been designed to reproduce physiological knee kinematics. It has been reported that alumina ceramic femoral components reduce polyethylene wear. Thus, medial pivot total knee prostheses with alumina ceramic femoral components were introduced. The purpose of this study was to evaluate the clinical results of patients who underwent newly introduced alumina medial pivot total knee arthroplasties (TKA). METHODS: We evaluated the clinical results of 107 alumina medial pivot TKAs in 80 consecutive patients with a mean follow-up period of 5 years. RESULTS: Alumina medial pivot TKAs provided significant improvements in the patients' Knee Society knee scores, function scores and post-operative ranges of motion compared with their pre operative statuses (each, P < 0.05). There was no statistical correlation between the change in maximum knee flexion and the increase in posterior condylar offset. Revision surgery was required in one knee due to a post-operative fracture of the tibial plateau after a fall that occurred 2 years postoperatively. No knees had aseptic loosening, osteolysis, or ceramic fractures. The survival rate was 98.6% at 5 years. CONCLUSIONS: This study demonstrates satisfactory mid-term clinical results for patients receiving the alumina medial pivot prosthesis. LEVEL OF EVIDENCE: Therapeutic study, Level IV. PMID- 22057352 TI - Anteromedial versus central single-bundle graft position: which anatomic graft position to choose? AB - PURPOSE: To compare the time-zero stability of an anatomic anteromedial (AM) single-bundle ACL reconstruction to an anatomic central (CTR) single-bundle ACL reconstruction. METHODS: Twelve (6 paired) hip to knee cadaveric specimens were studied. Using custom ACL computer navigation software, a Lachman test and a previously validated, navigated mechanized pivot shift test were performed on 4 separate experimental groups in each specimen: (1) intact ACL, (2) ACL deficient with total medial and lateral meniscectomy, (3) following anatomic AM single bundle ACL reconstruction, and (4) after anatomic CTR single-bundle ACL reconstruction. Maximum anterior tibial translation in each group was measured. RESULTS: Lachman: No significant difference was observed between the AM and CTR reconstructions (n.s.) or between reconstruction and the intact ACL (3.4 +/- 1.7 mm) (n.s.). Pivot Shift: Both the AM and CTR ACL reconstructions significantly reduced anterior translation relative to the ACL/menisci-deficient condition (lateral compartment: 8.9 +/- 3.8 mm and 6.75 +/- 4.6 mm vs. 17.25 +/- 3.5 mm, respectively; P < 0.001 and medial compartment: -3.0 +/- 5.3 mm vs. -3.7 +/- 5.7 mm vs. 6.2 +/- 6.7 mm, P < 0.05). There was also a significant difference between the AM (P < 0.001) and CTR (P < 0.05) ACL reconstructions and the intact ACL (2.8 +/- 4.4 mm) for lateral compartment translation. Further, no difference was found between lateral or medial compartment translations in the AM versus CTR reconstructions (n.s.). CONCLUSIONS: It has been shown that there was no difference in the time-zero biomechanical stability between an anatomic anteromedial and anatomic central single-bundle ACL reconstruction. Given the current debate on the best anatomic ACL reconstruction technique, anatomic socket position in either the anteromedial or central locations provides similar time zero biomechanics. PMID- 22057353 TI - Gender difference of the femoral kinematics axis location and its relation to anterior cruciate ligament injury: a 3D-CT study. AB - PURPOSE: The variation of distal femur morphology has been often reported, especially in relation to ACL injury. However, it remains unknown how morphological differences affect knee kinematics and ACL function. The location of the transcondylar axis, a common anatomical reference line, may be a significant aspect of morphological variation. It was hypothesized that the location of this axis would be different between genders, and between ACL-injured and non-injured subjects. METHODS: 3D CT scans of contralateral healthy femurs in 38 unilateral soft tissue injured patients (20 men/18 women, 26 ACL injury/12 non ACL injury (7 with PCL injuries and 5 with medial meniscus root tears)) were analyzed three-dimensionally. Condyle offset was calculated as the distance between the transcondylar axis and the anatomical axis of the femur. Condyle offset ratio (COR) was then calculated by dividing the condyle offset by the condyle radius. Gender and ACL-injured and non-injured group differences were assessed. RESULTS: Larger COR was found in women, 1.10 +/- 0.14, than men, 0.96 +/- 0.08. In women, the ACL-injured group had significantly larger COR than the non-ACL injury group, but no difference was found in men. CONCLUSION: COR is a unique morphological feature which is measureable from 3D CT. COR is larger in women, and could be a possible risk indicator for ACL injury in the female population. LEVEL OF EVIDENCE: III. PMID- 22057354 TI - Less femorotibial rotation and AP translation in deep-dished total knee arthroplasty. An intraoperative kinematic study using navigation. AB - PURPOSE: Hyper-congruent inserts have been proposed as another means of posterior stabilization in total knee arthroplasty. Their kinematics, partially unexplored, is reported to be possibly erratic. The objectives of the present study were to detect whether prostheses with such a constrained design would provide antero posterior (AP) stability without interfering with high flexion. METHODS: The kinematics of 10 knees replaced with hyper-congruent inserts was tested intra operatively with a specially designed navigation system (Praxim, La Tronche, Isere, France), to measure AP displacements of femoro-tibial contact points at knee flexion. RESULTS: Femoro-tibial contact points in full extension were in a posterior position compared to their initial position before implantation (8 +/- 6 mm medially, 15 +/- 10 mm laterally, P < 0.004). AP displacements were different from pre-operative displacements (3 +/- 4 mm vs -5 +/- 2 mm for the medial condyle, P < 0.01 and -2 +/- 6 mm vs -22 +/- 8 mm for the lateral condyle, P < 0.001). Forward rolling persisted in four cases, with the medial condyle being involved in three of them (9, 9, and 6 mm, respectively). Post-operative flexion of 122 degrees on average was not correlated with AP displacements. CONCLUSIONS: Hyper-congruent prostheses partially stabilized femoral condyles at knee flexion. Posterior displacements were reduced with no consequence on range of flexion. Posterior stabilization was imperfect, and paradoxical displacements were detected by navigation, which could therefore help optimize knee balance. LEVEL OF EVIDENCE: Diagnostic study, Level II. PMID- 22057355 TI - Evaluation of a simulated pivot shift test: a biomechanical study. AB - PURPOSE: Double-bundle anterior cruciate reconstructions have led to an increased interest in quantifying anterolateral rotatory stability. The application of combined internal rotation and valgus torques to the knee can more nearly recreate the anterolateral subluxation that occurs in the pivot shift test in vitro compared to coupled internal rotation torque and anterior tibial loads. METHODS: Twelve non-paired cadaveric knees were biomechanically tested with the ACL intact and sectioned. For each test state, six-degree-of-freedom positional data were collected for two simulated pivot shift loads consisting of a 5-Nm internal rotation torque coupled with either a 10-Nm valgus torque or an 88 N anterior tibial load at 0 degrees , 20 degrees , 30 degrees , 60 degrees , and 90 degrees of knee flexion. RESULTS: The coupled internal rotation and valgus torques produced a significant increase in anterolateral subluxation between the ACL intact and sectioned states at all tested angles except 90o (5.9 +/- 0.4 mm at 0 degrees , 4.3 +/- 0.6 mm at 20 degrees , 3.5 +/- 0.6 mm at 30 degrees , 2.1 +/- 0.6 mm at 60 degrees ). The coupled internal rotation and an anterior tibial load produced significant increases between the ACL intact and sectioned states at all tested angles except 30o (5.4 +/- 0.5 mm at 0 degrees , 3.7 +/- 0.5 mm at 20 degrees , 2.1 +/- 0.8 mm at 60 degrees , 1.4 +/- 0.3 mm at 90 degrees ). CONCLUSIONS: We found that the coupled internal rotation and valgus torques best recreated the anterolateral subluxation that occurs in the pivot shift in vitro. This study describes an anterolateral subluxation test for ACL integrity in the laboratory setting. PMID- 22057356 TI - Factors affecting anterior knee pain following anatomic double-bundle anterior cruciate ligament reconstruction. AB - PURPOSE: The purpose of this study was to evaluate the prevalence of anterior knee pain in anatomic double-bundle anterior cruciate ligament (ACL) reconstruction and to identify critical factors affecting postoperative anterior knee pain development. METHODS: Subjects comprised 171 patients (171 knees) who underwent anatomic double-bundle ACL reconstruction with a follow-up period of >=2 years. The procedure used bone-patellar tendon-bone plus gracilis tendon (BTB G) in 56 knees, semitendinosus tendon (ST) in 71 knees, and ST-G in 44 knees. Clinical results and prevalence and severity of anterior knee pain were assessed at 3 months and 2 years postoperatively. Clinical variables influencing anterior knee pain development at each postoperative period were subjected to univariate analysis, followed by logistic regression analysis to identify risk factors for anterior knee pain. RESULTS: Overall prevalences of anterior knee pain at 3 months and 2 years postoperatively were 42.0 and 11.1%, respectively. Use of BTB G graft represented the highest prevalence of anterior knee pain between the 3 different grafts (P = 0.001); however, this statistical significance disappeared at 2 years postoperatively. Prevalence of postoperative extension deficit was significantly higher in anterior knee pain-positive cohort than in anterior knee pain-negative cohort at 3 months postoperatively. Level of quadriceps strength was significantly lower, and Lysholm score was significantly worse in anterior knee pain-positive cohort than in anterior knee pain-negative cohort at 2 years postoperatively. According to logistic regression analysis, knee extension deficit was a predisposing factor for the development of anterior knee pain at 3 months postoperatively (odds ratio, 2.76; P = 0.004); however, there was no significant predisposing factor for anterior knee pain at 2 years postoperatively. CONCLUSIONS: Knee extension deficit was an important predisposing factor for postoperative anterior knee pain in the early postoperative period, and anterior knee pain was associated with impaired quadriceps function and inferior subjective results over 2 years postoperatively. Early recovery of full extension may prevent postoperative development of anterior knee pain and achieve successful outcomes for ACL reconstruction. LEVEL OF EVIDENCE: Retrospective comparative study, Level III. PMID- 22057357 TI - Arthroscopic fixation of displaced greater tuberosity fracture of the proximal humerus. AB - Single-row fixation with two inverted mattress stitches was used to treat displaced fracture of the greater tuberosity of the proximal humerus. The inverted mattress sutures were passed through the bone-tendon junction of the fragment by suture passer and crossed over the bone fragment, locking the suture ends into the lateral cortex. PMID- 22057358 TI - Association of clinical and pathological variables with survival in thymoma. AB - Our aim was to evaluate clinical and pathological features in prognosis of thymoma patients with particular emphasis on patients with myasthenia gravis (MG). From 1995 to 2010, 140 thymoma patients (women/men: 63/77) with a median age of 46 years (11-80 years) were admitted to our institution. According to World Health Organization (WHO), there were 23 (17%) type A, 12 (9%) type AB, 24 (17%) type B1, 42 (31%) type B2 and 36 (26%) type B3. The distribution of Masaoka stages I, II, III and IV was 24 (17%), 71 (51%), 18 (13%) and 27 (19%), respectively. MG coexisted in 61% of patients. After a mean follow-up of 34 months (1-158 months), 102 (73%) patients are alive and well while 14 (10%) are alive with disease. Twenty-three patients (16%) have died, only 9 died of thymoma. In univariate analyses, completeness of resection (P < .001), WHO histology (P = .008), Masaoka stage (P < .001) and MG (P = .002) were significant prognostic factors for progression-free survival (PFS). Young age (P = .008); Masaoka stages 1 and 2 (P = .039); WHO types A, AB and B1 (P = .031); complete resection (P = .024) and presence of MG (P = .05) significantly correlated with overall survival (OS). In multivariate analysis, Masaoka stages 1 and 2 (P = .038) and presence of MG (P = .01) were significantly correlated with a longer PFS; MG (P = .021) and WHO subtype (P = .022) were found to be significant prognostic factors for OS. Adjuvant radiotherapy improved neither OS nor PFS in completely resected stage 2 thymoma. Masaoka staging, WHO and MG are major determinants of prognosis in Turkish thymoma patients. Additionally, radiotherapy did not provide survival advantage to stage 2 patients with complete resection. PMID- 22057359 TI - TP53 mutation is not an independent prognostic factor in patients with mantle cell lymphoma at advanced stage. AB - Mantle cell lymphoma (MCL) is incurable in most patients. Several molecular markers have been identified as possible prognostic factors in MCL, including TP53 mutations. Direct sequencing was used to detect 32 cases with leukemic presentation of MCL form exons 2-11 in order to explore the prognostic significance of TP53 mutations in Chinese patients. Within the MCL cohort, 6(18.8%) patients harbored TP53 mutations. TP53 mutations in the absence of del(17p13) were found in 5.0% of MCL cases (1 of 20) compared with 83.3% of MCL cases (5 of 6) with del(17p13). Compared with patients without TP53 mutations, TP53 mutations were associated with risk factors including age, higher serum lactate dehydrogenase, lymphocytosis, high-risk (HR) international prognostic index, HR mantle cell lymphoma international prognostic index, complex karyotype, and higher occurrence of TP53 deletions. In contrast, it is found that TP53 mutations were correlated with mutated immunoglobulin heavy-chain variable region status and CD38 negative. TP53 mutations were the significant factors in predicting survival in univariate analysis, but unfortunately they were not the unique variable associated with overall survival by multivariate Cox regression analysis. TP53 mutation was insufficiently an independent prognostic factor in patients with MCL at advanced stage. PMID- 22057360 TI - Carbon/metal nanotubes with tailored order and configuration by direct carbonization of inverse block copolymer micelles inside nanoporous alumina. AB - Carbonaceous nanotubes decorated with metal nanoparticles were obtained by heating inverse block copolymer micelles loaded with metal precursors inside nanoporous alumina. Simple changes in the applied temperature profile allowed tailoring of the wall morphology of the nanotubes and the spatial arrangement of the metal nanoparticles. PMID- 22057361 TI - Phrenic nerve injury after image-guided insertion of a tunnelled right internal jugular central venous catheter. AB - Central venous catheters (CVC) are now commonly inserted by radiologists. Although complications are infrequent, they must be avoided where possible and recognized when they occur. We present a 10-year-old boy who developed right hemidiaphragmatic paralysis, requiring surgical plication, following US-guided insertion of a tunnelled right internal jugular CVC. The needle trajectory for internal jugular puncture must be planned to avoid the phrenic nerve. PMID- 22057362 TI - Quality assurance: a comparison study of radiographic exposure for neonatal chest radiographs at 4 academic hospitals. AB - BACKGROUND: Little is known about exposure differences among hospitals. Large differences might identify outliers using excessive exposure. OBJECTIVE: We used the newly described exposure index and deviation index to compare the difference in existing radiographic exposures for neonatal portable chest radiographs among four academic children's hospitals. MATERIALS AND METHODS: For each hospital we determined the mean exposure index. We also set target exposure indices and then measured the deviation from this target. RESULTS: There was not a large difference in exposure index among sites. No site had an exposure index mean that was more than twice or less than half that of any other site. For all four sites combined, 92% of exposures had a deviation index within the range from -3 to +3. Thus exposures at each hospital were consistently within a reasonable narrow spectrum. CONCLUSION: Mean exposure index differences are caused by operational differences with mean values that varied by less than 50% among four hospitals. Ninety-two percent of all exposures were between half and double the target exposure. Although only one vendor's equipment was used, these data establish a practical reference range of exposures for neonatal portable radiographs that can be recommended to other hospitals for neonatal chest radiographs. PMID- 22057363 TI - Positional and temporal clustering in serial order memory. AB - The well-known finding that responses in serial recall tend to be clustered around the position of the target item has bolstered positional-coding theories of serial order memory. In the present study, we show that this effect is confounded with another well-known finding--that responses in serial recall tend to also be clustered around the position of the prior recall (temporal clustering). The confound can be alleviated by conditioning each analysis on the positional accuracy of the previously recalled item. The revised analyses show that temporal clustering is much more prevalent in serial recall than is positional clustering. A simple associative chaining model with asymmetric neighboring, remote associations, and a primacy gradient can account for these effects. Using the same parameter values, the model produces reasonable serial position curves and captures the changes in item and order information across study-test trials. In contrast, a prominent positional coding model cannot account for the pattern of clustering uncovered by the new analyses. PMID- 22057365 TI - Enteropathogens in acute diarrhea: a general practice-based study in a Nordic country. AB - The epidemiology of infectious diarrhea influences the microbiological investigation of the disease, and is best elucidated through prospective studies. We undertook such a study in a Nordic country. Patients of all age groups who had acute diarrhea were recruited prospectively from general practice clinics in Iceland. They completed a questionnaire and provided stool samples for the detection of pathogenic viruses, bacteria, and parasites. Of the 464 recruited patients, 211 (45%) had 224 infections. The most common pathogens were calici- and rotaviruses (23% and 18% of 224 infections, respectively), Campylobacter jejuni (17%), Cryptosporidium species (12%), and Salmonella serotypes (10%). Other agents found were Giardia lamblia, astro- and adenoviruses, and Yersinia enterocolitica. Viral pathogens were associated with vomiting, illness for <=7 days, and younger age groups, while bacterial pathogens were associated with fever, rectal pain, and local or foreign travel, and parasitic pathogens with illness for >7 days. Detection rates for viral infections in the elderly and for Cryptosporidium species were higher than expected. Our study indicates the existence of regional differences in pathogen prevalence that should be taken into account when implementing guidelines for stool testing in patients with acute diarrheal disease. PMID- 22057366 TI - Polymorph and isomer conversion of complexes based on CuI and PPh3 easily observed via luminescence. AB - Reactions between copper(I) iodide and triphenylphosphine have been explored in solution and in the solid state and six luminescent coordination complexes have been obtained and characterized by X-ray diffraction and UV-vis spectroscopy and photophysics. Solid-state reactions of CuI with PPh(3) in different conditions (kneading, vapour digestion) and stoichiometries resulted in the formation of high ratio ligand:metal compounds while tetrameric structures could be obtained only by solution reactions. Crystal structures were determined by single crystal X-ray diffraction while purity of the bulk product was checked by powder diffraction (XRPD). Three different tetrameric structures with 1:1 stoichiometry have been synthesized: two closed cubane-type polymorphs [CuI(PPh(3))](4) (form 1a) and [CuI(PPh(3))](4) (form 1b) and an open step-like isomer [CuI(PPh(3))](4) (form 2). The conversions between the polymorphs and isomers have been studied and characterized by XRPD. The most stable form [CuI(PPh(3))](4) (form 1b) can convert into the open step-like isomer [CuI(PPh(3))](4) (form 2) in a slurry experiment with EtOH or CH(2)Cl(2) or AcCN and converts back into [CuI(PPh(3))](4)1b when exposed to vapors of toluene. At room temperature all the tetrameric compounds exhibit luminescence in the solid state and, notably, the two polymorphs show a dissimilar dual emission at low temperature. The luminescence features in the solid state seem to be peculiarly related to the presence of the aromatic phosphine ligand and depend on the Cu-Cu distance in the cluster. PMID- 22057368 TI - Arousal and affective differences between student gamblers and non-gamblers during a card game. AB - The current study examined the differences in arousal (physiologically and subjectively) between gamblers and non-gamblers. Thirty students from a mid-sized university took part in the study for a chance to win money in a gambling task. Nearly half of the participants identified themselves as non-gamblers and slightly more than half of the participants considered themselves gamblers. Findings indicated that gamblers experienced a significantly higher increase in physiological arousal (heart rate) compared to non-gamblers during the gambling experience. The results suggests the possibility that physiological arousal may play a role in the appeal of gambling to certain types of people. Furthermore, when gamblers suffered a loss at the end of the game, they reported feeling worse as compared to the non-gamblers and relative to their state before playing. Moreover, this affective change explained 28.6% of the variance in gambling behavior according to self-reports. Findings suggest that gamblers in our study may have been more personally invested in the gambling tasks, such that losing was more disappointing to the habitual gamblers than the non-gamblers. PMID- 22057367 TI - Rescue of replication failure by Fanconi anaemia proteins. AB - Chromosomal aberrations are often associated with incomplete genome duplication, for instance at common fragile sites, or as a consequence of chemical alterations in the DNA template that block replication forks. Studies of the cancer-prone disease Fanconi anaemia (FA) have provided important insights into the resolution of replication problems. The repair of interstrand DNA crosslinks induced by chemotherapy drugs is coupled with DNA replication and controlled by FA proteins. We discuss here the recent discovery of new FA-associated proteins and the development of new tractable repair systems that have dramatically improved our understanding of crosslink repair. We focus also on how FA proteins protect against replication failure in the context of fragile sites and on the identification of reactive metabolites that account for the development of Fanconi anaemia symptoms. PMID- 22057370 TI - Tsunami lung. AB - We encountered three cases of lung disorders caused by drowning in the recent large tsunami that struck following the Great East Japan Earthquake. All three were females, and two of them were old elderly. All segments of both lungs were involved in all the three patients, necessitating ICU admission and endotracheal intubation and mechanical ventilation. All three died within 3 weeks. In at least two cases, misswallowing of oil was suspected from the features noted at the time of the detection. Sputum culture for bacteria yielded isolation of Stenotrophomonas maltophilia, Legionella pneumophila, Burkholderia cepacia, and Pseudomonas aeruginosa. The cause of tsunami lung may be a combination of chemical induced pneumonia and bacterial pneumonia. PMID- 22057371 TI - Public awareness about the connection between depression and physical health: specifically heart disease. AB - The medical community continues to acknowledge a connection between depression and physical health, for example, cardiac disease. This study addresses public awareness about depression's effects on physical health, the relationship between cardiac disease and depression, and preferred sources of health information, in an effort to inform future health education programs. A survey, administered to 816 adults ages 40-69, focused on public awareness, perception of depression as an illness, its impact on other illnesses such as heart disease, and sources of health information. (1) Eighty-three percent (83%) of respondents felt depression was an illness; (2) a slightly higher percentage (85.8%) felt a mental disorder, like depression, could affect the course of a physical illness; (3) respondents' awareness of links between depression and cardiac disease ranged from 29.8% (awareness of depression as a risk factor for coronary artery disease) to 31.6% (awareness that depression can increase the risk of having a second heart attack); (4) print media were the most frequently cited sources of health information (22.7%); and (5) more highly educated respondents were more informed about depression than respondents with less education. Although a majority of respondents (1) recognized depression as an illness (2) thought it could complicate recovery from a physical illness, less than a third of them were aware of links between cardiac disease and depression. Demographic groups differed in their preferred sources of health information, especially across educational levels, demonstrating a need for targeted health educational outreach in efforts to reach a variety of populations. PMID- 22057372 TI - Methylation status of lamin A/C in gastric cancer cell lines. AB - BACKGROUND/AIMS: Epigenetic regulations play a role in the development and progression of cancer. Therefore, discovering novel epigenetically regulated genes could provide useful information in understanding cancer. Lamin A/C is an intermediate filament protein whose expression is reported to be suppressed in tissues of gastro-intestinal malignancies. We examined expression of lamin A/C in gastric and colorectal cancer cell lines and its association with DNA methylation. METHODOLOGY: The methylation status of CpG island in 19 gastric, 5 colorectal cancer cells and 1 normal colon cell line were examined with methylation-specific PCR using paired methylated and unmethylated primers. The level of mRNA expression of lamin A/C was detected using RT-PCR. RESULTS: Eighteen gastric cancer cell lines showed 95% unmethylation of lamin A/C and 1 cell line showed partial methylation. In colorectal cancer, only 1 out of 5 cancer cell lines (20%) was partially methylated and the remaining cell lines, including 1 normal colon cell line was unmethylated. With RT-PCR, all cell lines demonstrated mRNA expression of lamin A/C regardless of methylation status. CONCLUSIONS: We observed that the expression of lamin A/C was not suppressed in gastrointestinal cancer cell lines different from hematologic malignant cells and it is not regulated through DNA methylation. PMID- 22057373 TI - Outcome of laparoscopy-assisted gastrectomy vs. open gastrectomy for gastric cancer: a retrospective comparative study. AB - BACKGROUND/AIMS: Laparoscopy-assisted gastrectomy is still controversial because of scant evidence of safety and feasibility. The objective of this study was to assess the feasibility of using the laparoscopy-assisted gastrectomy in treating gastric cancer and evaluate its outcome compared with conventional open gastrectomy. METHODOLOGY: Between November 2005 and November 2007, 31 patients underwent laparoscopy-assisted gastrectomy and 95 patients underwent open gastrectomy for gastric cancer. Clinicopathological characteristics, total number of lymph nodes retrieved and overall survival were retrospectively compared between the two groups. RESULTS: No significant differences were found in the total number of retrieved lymph nodes (26.3+/-11.6 vs. 27.6+/-10.4) between the two groups. The mean follow-up and overall survival time after surgery was 30.8 (range 4-47) months and 40.9 months (95% confidence interval, 38.5-43.2 months), respectively. The mean survival time in patients of the laparoscopy-assisted gastrectomy group was 42.4 months vs. 40.3 months in patients of the open surgery alone group (p=0.457). A logistic regression model revealed that node invasion (hazard ratio 1.149, p<0.001) and serosal invasion (hazard ratio 4.623, p=0.044) were associated with overall survival of gastric cancer patients. CONCLUSIONS: Laparoscopy-assisted gastrectomy with D2 lymph node dissection is a safe and feasible procedure with adequate lymphadenectomy for the treatment of gastric cancer. PMID- 22057374 TI - Cystatin C is a good predictor of hepatorenal syndrome and survival in patients with cirrhosis who have normal serum creatinine levels. AB - BACKGROUND/AIMS: We evaluated the usefulness of cystatin C as a prognostic marker in patients with liver cirrhosis and normal serum creatinine. METHODOLOGY: We retrospectively analyzed prospectively enrolled patients with liver cirrhosis and normal serum creatinine from February 2007 to March 2008. We checked liver function and kidney variables including serum creatinine, cystatin C and glomerular filtration rate from 51Cr-EDTA on the same day for all patients. The endpoints of the study were either development of hepatorenal syndrome or mortality. RESULTS: In total, 112 patients with liver cirrhosis were enrolled in the study (87 men and 25 women, age 52 +/- 12 years). Twelve (11%), 59 (53%) and 41 (36%) patients were in Child-Pugh class A, B and C, respectively. Cystatin C was better correlated with glomerular filtration rate from 51Cr-EDTA than creatinine. The 1-year cumulative incidence of hepatorenal syndrome and the 1 year survival rate of patients were 20.5% and 79.5%, respectively. Cystatin C, Model for End-Stage Liver Disease and serum sodium were the independent predictive factors for hepatorenal syndrome. Cystatin C, serum sodium and prothrombin time were the independent factors for predicting survival. CONCLUSIONS: In patients with liver cirrhosis and normal creatinine levels, cystatin C is a useful marker for predicting hepatorenal syndrome and survival. PMID- 22057375 TI - Inhibition of trauma-associated inflammatory liver damage by blocking NF-kappaB activity. AB - BACKGROUND/AIMS: NF-kappaB protein family members act as transcription facts and play a key role in regulating the immune response to infection and inflammatory signals. We proposed to determine the role of NF-kappaB in the development of trauma-associated liver damage and inflammation. METHODOLOGY: NF-kappaB DNA binding activity was inhibited using double-stranded oligodeoxynucleotides (ODN). A total of 288 Wistar rats were randomly divided into four groups: control (C), traumatic inflammation (T), traumatic inflammation plus NF-kappaB decoy (ODN) and traumatic inflammation plus mutant NF-kappaB decoy ODN (mODN). RESULTS: Our data shows that inhibition of NF-kappaB activation significantly reduces liver tissue damage as evidenced by serum ALT levels and histological changes using both light microscopy and transmission electron microscopy. Furthermore, EMSA results showed that NF-kappaB activation was reduced in Group ODN rats compared to Group T and Group mODN rats. Expression of TNF-a and IL-6 protein in Group ODN rats were also reduced compared to Group T and Group mODN rats. We demonstrated that NF-kappaB plays an important role in trauma-associated inflammation and liver tissue damage. CONCLUSIONS: Suppressing NF-kappaB activation effectively reduces the release of the pro-inflammatory cytokines TNF-a and IL-6 following liver trauma. PMID- 22057376 TI - Recipient splenic artery utilization for arterial re-anastomosis in living donor liver transplantation: single-center experience. AB - Thrombosis of recipient hepatic artery is a life threatening complication for liver transplantation. The etiology of hepatic arterial thrombosis is multi factorial and can be caused by intimal dissection, poor surgical technique and coagulopathies. The patency of hepatic arterial flow is very important for both graft survival and patient survival. Intraoperative diagnosis of inadequate hepatic arterial flow found with Doppler ultrasonography is essential in order to achieve good results after liver transplantation. Urgent re-anastomosis is necessary when the arterial blood flow is insufficient. We performed 317 living donor liver transplantations from July 2004 to July 2011. We used recipient splenic artery for hepatic artery reconstruction in six patients. These six patients were included in this study. Using the recipient splenic artery is a simple, safe and practical alternative for hepatic artery re-anastomosis in living donor liver transplantations. PMID- 22057377 TI - Management of choledochal cysts in adults: a retrospective analysis of 23 patients. AB - BACKGROUND/AIMS: Choledochal cysts are rare congenital anomalies of the pancreaticobiliary system, whose etiology remains unknown. We aimed to review patients with choledochal cysts and to compare our results with current literature. METHODOLOGY: Twenty-three patients diagnosed as having choledochal cysts between January 2004 and July 2010 were evaluated retrospectively. RESULTS: Thirteen patients had type I (56.5%), 3 patients type II (13%), 3 patients type III (13%), 1 patient type IV-A (8.3%) and the remaining 3 patients had type V (13%) choledochal cysts. All patients with type I cysts underwent cyst excision with Roux-en-Y hepaticojejunostomy. Two patients with type II cysts underwent cyst excision with choledochoduodenostomy, whereas cyst excision with T-tube drainage was applied to the other. Endoscopic unroofing was performed type III cysts. The patient with type IV-A cyst was not eligible for surgery due to low cardiopulmonary performance status but ERCP was applied successfully more than 3 times for the extraction of the stones which fell from the intrahepatic ducts into the common bile duct. Patients with Type V cysts underwent left hepatectomy, choledocoduodenostomy and cadaveric liver transplantation, respectively. Wound infection developed in 5 patients and anastomotic leakage occurred in 3; one died from sepsis. CONCLUSIONS: Choledochal cysts are rare congenital malformations. Although treatment varies depending on the type of the cysts, complete excision of the cysts should be performed if possible. PMID- 22057378 TI - Glue embolization for endoscopically unmanageable gastrointestinal haemorrhage. AB - BACKGROUND/AIMS: To evaluate the clinical feasibility of embolization with n butyl cyanoacrylate (NBCA) for endoscopically unmanageable non-variceal gastrointestinal hemorrhage (GIH). METHODOLOGY: Between June 2004 and May 2009, 61 patients with confirmed acute upper and/or lower GIH underwent emergency embolization for haemorrhage control; NBCA was used in 28 of these patients, all of whom were in shock despite receiving blood transfusions. The results were studied retrospectively. Clinical parameters and embolization data were assessed for technical success, clinical success and outcome. RESULTS: Technical success was achieved in all patients. Clinical success was achieved in 19 (68%) of the 28 patients. The mortality rate was 25% (7 patients). The cause of death was disseminated intravascular coagulation (DIC) in 6 patients and heart failure in 1. The presence of coagulopathy or DIC significantly decreased the degree of clinical success (p=0.015, p=0.001, respectively) and increased the mortality rate (p=0.013, p<0.001, respectively). Unfortunately, 86% patients who had DIC before embolization, died. CONCLUSIONS: NBCA embolization is technically feasible and is effective for the control of haemorrhage in endoscopically unmanageable GIH. However, the presence of coagulopathy or DIC significantly decreases the clinical success and increases the mortality rate. PMID- 22057379 TI - Electrophysiological studies in newly onset type 2 diabetes without visible vascular retinopathy. AB - The purpose of this study was to investigate the early alterations of retinal function, assessed with electrophysiology, in newly onset type 2 diabetes patients without vascular retinopathy. Seventeen patients with newly diagnosed type 2 diabetes (duration 7+/-3 months), without any vascular retinopathy in fundus photographs, were examined with full-field electroretinogram (ERG) and multifocal ERG (mfERG). The results were compared with those of age-matched subjects without diabetes. In the dark-adapted full-field ERG, the a-wave and the 30-Hz flicker implicit times were delayed in diabetes patients compared to controls, P=0.001 and P=0.020. In the first-order kernel of the mfERG, the first positive wave, P1, was delayed in all areas measured. The electrophysiological examinations demonstrate early alterations of retinal function characterised by a delayed a-wave implicit time in the dark-adapted full-field ERG, representing the rod signalling, and alterations in the multifocal ERG reflecting cone and/or postreceptoral function. PMID- 22057380 TI - Medical management of ischemic stuttering priapism: a contemporary review of the literature. AB - Priapism is defined as a prolonged and persistent erection of the penis without sexual stimulation. This is a poorly understood disease process with little information on the pathophysiology of this erectile disorder. Complications from this disorder are devastating due to the irreversible erectile damage and resultant erectile dysfunction (ED). Stuttering priapism, though relatively rare, affects a high prevalence of men with sickle-cell disease (SCD) and presents a challenging problem with guidelines for treatment lacking or resulting in permanent ED. The mechanisms involved in the development of priapism in this cohort are poorly characterized; therefore, medical management of priapism represents a therapeutic challenge to urologists. Additional research is warranted, so we can effectively target treatments for these patients with prevention as the goal. This review gives an introduction to stuttering priapism and its clinical significance, specifically with regards to the patient with SCD. Additionally, the proposed mechanisms behind its pathophysiology and a summary of the current and future targets for medical management are discussed. PMID- 22057381 TI - Altered histone retention and epigenetic modifications in the sperm of infertile men. PMID- 22057382 TI - Health-related quality of life outcomes in Scandinavian patients after radical prostatectomy or watchful waiting: a critical appraisal. PMID- 22057383 TI - Differentiation of murine male germ cells to spermatozoa in a soft agar culture system. AB - Establishment of an in vitro system that allows the development of testicular germ cells to sperm will be valuable for studies of spermatogenesis and future treatments for male infertility. In the present study, we developed in vitro culture conditions using three-dimensional agar culture system (SACS), which has the capacity to induce testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation. Seminiferous tubules from testes of 7-day-old mice were enzymatically dissociated, and intratubular cells were cultured in the upper layer of the SACS in RPMI medium supplemented with fetal calf serum (FCS). The lower layer of the SACS contained only RPMI medium supplemented with FCS. Colonies in the upper layer were isolated after 14 and 28 days of culture and were classified according to their size. Immunofluorescence and real-time PCR were used to analyse specific markers expressed in undifferentiated and differentiated spermatogonia (Vasa, Dazl, OCT-4, C-Kit, GFR alpha-1, CD9 and alpha-6-integrin), meiotic cells (LDH, Crem-1 and Boule) and post-meiotic cells (Protamine-1, Acrosin and SP-10). Our results reveal that it is possible to induce mouse testicular pre-meiotic germ cell expansion and induce their differentiation to spermatozoa in SACS. The spermatozoa showed normal morphology and contained acrosomes. Thus, our results demonstrate that SACS could be used as a novel in vitro system for the maturation of pre-meiotic mouse germ cells to post-meiotic stages and morphologically-normal spermatozoa. PMID- 22057384 TI - High-Tc ferromagnetism in a Co-doped ZnO system dominated by the formation of a zinc-blende type Co-rich ZnCoO phase. AB - The modulation of the distribution of magnetic ions embedded in the host is crucial for the functionality of dilute magnetic semiconductors. Through an element-specific structural characterization, we observe the formation and enhancement of an unrevealed Co-doped ZnO phase and consequently magnetic properties from paramagnetism to ferromagnetism are controlled by surface modification. PMID- 22057385 TI - Comparison of the tibiofemoral rotational alignment after mobile and fixed bearing total knee arthroplasty. AB - PURPOSE: The anatomical landmark for the anteroposterior (AP) axis of the proximal tibia and its variability was investigated in order to determine whether a certain landmark could be employed as a reference axis for the proximal tibia after the rotating platform mobile bearing and fixed bearing total knee arthroplasties (TKAs). METHODS: Eighty primary osteoarthritic knees were randomized to undergo either rotating platform mobile bearing (Group A, n = 40) or fixed bearing (Group B, n = 40) TKAs, and were followed up for 31 and 30 months, respectively. The AP axes were defined for the distal femur, proximal tibia, ankle, and each TKA component on the reconstructed CT scan and the angles between the distal femoral AP axis and those of each bone or component were estimated. Clinical and radiographic outcomes were evaluated during the follow up. RESULTS: A significant difference was seen between the preoperative and postoperative rotational position of the proximal tibia relative to the distal femur following rotating platform mobile bearing TKA (P = 0.014) whereas no such difference was seen after fixed bearing TKA. The mean postoperative alignment of the tibia differed between the two groups (Group A:Group B = -2.9:0.2, P = 0.010) and its variability was significantly greater in group A (P < 0.001). There were no differences in the clinical outcomes including range of motion, knee society score, function score, HSS, and WOMAC score as well as the mean postoperative coronal tibiofemoral alignment between the two groups. CONCLUSION: The unpredictable change in the rotational axis of the tibia and its broad variability after rotating platform mobile bearing TKA may provide a warning against the use of a fixed landmark for establishing tibial rotational alignment. PMID- 22057386 TI - Over-the-top double-bundle revision ACL reconstruction. AB - Revision ACL presents many technical issues that are not seen in the primary ACL reconstruction. A variety of surgical techniques for revising ACL reconstruction have been described in the literature to address these concerns. The purpose of this article is to present a novel technique consisting in a non-anatomic double bundle ACL revision reconstruction, using a fresh-frozen Achilles tendon allograft with soft tissue fixation. This technique is a valid treatment option when faced with a complex scenario such as ACL revision surgery. PMID- 22057387 TI - Solution-processed small-molecule solar cells with 6.7% efficiency. AB - Organic photovoltaic devices that can be fabricated by simple processing techniques are under intense investigation in academic and industrial laboratories because of their potential to enable mass production of flexible and cost-effective devices. Most of the attention has been focused on solution processed polymer bulk-heterojunction (BHJ) solar cells. A combination of polymer design, morphology control, structural insight and device engineering has led to power conversion efficiencies (PCEs) reaching the 6-8% range for conjugated polymer/fullerene blends. Solution-processed small-molecule BHJ (SM BHJ) solar cells have received less attention, and their efficiencies have remained below those of their polymeric counterparts. Here, we report efficient solution processed SM BHJ solar cells based on a new molecular donor, DTS(PTTh(2))(2). A record PCE of 6.7% under AM 1.5 G irradiation (100 mW cm(-2)) is achieved for small-molecule BHJ devices from DTS(PTTh(2))(2):PC(70)BM (donor to acceptor ratio of 7:3). This high efficiency was obtained by using remarkably small percentages of solvent additive (0.25% v/v of 1,8-diiodooctane, DIO) during the film-forming process, which leads to reduced domain sizes in the BHJ layer. These results provide important progress for solution-processed organic photovoltaics and demonstrate that solar cells fabricated from small donor molecules can compete with their polymeric counterparts. PMID- 22057388 TI - Universal energy-level alignment of molecules on metal oxides. AB - Transition-metal oxides improve power conversion efficiencies in organic photovoltaics and are used as low-resistance contacts in organic light-emitting diodes and organic thin-film transistors. What makes metal oxides useful in these technologies is the fact that their chemical and electronic properties can be tuned to enable charge exchange with a wide variety of organic molecules. Although it is known that charge exchange relies on the alignment of donor and acceptor energy levels, the mechanism for level alignment remains under debate. Here, we conclusively establish the principle of energy alignment between oxides and molecules. We observe a universal energy-alignment trend for a set of transition-metal oxides--representing a broad diversity in electronic properties- with several organic semiconductors. The trend demonstrates that, despite the variance in their electronic properties, oxide energy alignment is governed by one driving force: electron-chemical-potential equilibration. Using a combination of simple thermodynamics, electrostatics and Fermi statistics we derive a mathematical relation that describes the alignment. PMID- 22057389 TI - Lack of correlation between catalytic efficiency and basicity of amines during the reaction of aryl methyl ketones with DMF-DMA: an unprecedented supramolecular domino catalysis. AB - 1-Methylimidazole exhibits an unusually high efficiency in promoting the reaction of aryl methyl ketones with DMF-DMA to form (2E)-1-aryl-3-dimethylamino-2 propenones which lacks correlation between the catalytic efficiency and the basicity of 1-methylimidazole in comparison to other amines. An unprecedented supramolecular domino catalysis rationalises the lack of correlation between the catalytic efficiency and basicity of the amines. The supramolecular assemblies have been characterized by mass-spectrometric ion fishing. The time-dependent increase/decrease in the concentration (ion current) of the supramolecular species consolidated the mechanism. PMID- 22057390 TI - Two free radical pathways mediate chemical hypoxia-induced glutamate release in synaptosomes from the prefrontal cortex. AB - It has been known that the inhibition of mitochondrial cytochrome c oxidase is one of the earliest events occurring under hypoxia and this inhibition can lead to neuronal damages. Thus, the cytochrome c oxidase inhibitor sodium cyanide (NaCN) is widely used to produce a model of chemical hypoxia by inhibiting this enzyme. However, the downstream signaling pathways of the inhibition of the cytochrome c oxidase remain to be studied. In the present paper, we used sodium cyanide to mimic the inhibition of the mitochondrial cytochrome c oxidase and studied its effect on glutamate release in synaptosomes from the prefrontal cortex using on-line fluorimetry. We also further investigated the mechanisms underlying the enhancing effect of sodium cyanide on glutamate release using pharmacological approaches combined with other techniques. The results showed that sodium cyanide significantly increased glutamate release from synaptosomes of prefrontal cortex; the broad-spectrum free radical scavenger MnTBAP and melatonin completely abolished the effect of sodium cyanide on glutamate release; the H2O2-NMDA receptor pathway mediated one part, whereas the lipid peroxyl radicals-ATP synthase pathway mediated another part of the sodium cyanide-induced glutamate release; scavenging H2O2 and enhancing ATP synthase activity could completely abolish the sodium cyanide-induced glutamate release. PMID- 22057391 TI - Acquisition of mitochondrial dysregulation and resistance to mitochondrial mediated apoptosis after genotoxic insult in normal human fibroblasts: a possible model for early stage carcinogenesis. AB - Acquisition of death-resistance is critical in the evolution of neoplasia. Our aim was to model the early stages of carcinogenesis by examining intracellular alterations in cells that have acquired apoptosis-resistance after exposure to a complex genotoxin. We previously generated sub-populations of BJ-hTERT human diploid fibroblasts, which have acquired death-resistance following exposure to hexavalent chromium [Cr(VI)], a broad-spectrum genotoxicant. Long-term exposure to certain forms of Cr(VI) is associated with respiratory carcinogenesis. Here, we report on the death-sensitivity of subclonal populations derived from clonogenic survivors of BJ-hTERT cells treated with 5 MUM Cr(VI) (DR1, DR2), or selected by dilution-based cloning without treatment (CC1). Following Cr(VI) treatment, CC1 cells downregulated expression of the anti-apoptotic protein Bcl-2 and exhibited extensive expression of cleaved caspase 3. In contrast, the DR cells exhibited no cleaved caspase 3 expression and maintained expression of Bcl 2 following recovery from 24 h Cr(VI) exposure. The DR cells also exhibited attenuated mitochondrial-membrane depolarization and mitochondrial retention of cytochrome c and SMAC/DIABLO following Cr(VI) exposure. The DR cells exhibited less basal mtDNA damage, as compared to CC1 cells, which correlates with intrinsic (non-induced) death-resistance. Notably, there was no difference in p53 protein expression before or after treatment among all cell lines. Taken together, our data suggest the presence of more resilient mitochondria in death resistant cells, and that death-resistance can be acquired in normal human cells early after genotoxin exposure. We postulate that resistance to mitochondrial mediated cell death and mitochondrial dysregulation may be an initial phenotypic alteration observed in early stage carcinogenesis. PMID- 22057392 TI - A conserved cysteine cluster, essential for transcriptional activity, mediates homodimerization of human metal-responsive transcription factor-1 (MTF-1). AB - Metal-responsive transcription factor-1 (MTF-1) is a zinc finger protein that activates transcription in response to heavy metals such as Zn(II), Cd(II) and Cu(I) and is also involved in the response to hypoxia and oxidative stress. MTF-1 recognizes a specific DNA sequence motif termed the metal response element (MRE), located in the promoter/enhancer region of its target genes. The functional domains of MTF-1 include, besides the DNA-binding and activation domains and signals for subcellular localization (NLS and NES), a cysteine cluster 632CQCQCAC638 located near the C-terminus. Here we show that this cysteine cluster mediates homodimerization of human MTF-1, and that dimer formation in vivo is important for basal and especially metal-induced transcriptional activity. Neither nuclear translocation nor DNA binding is impaired in a mutant protein in which these cysteines are replaced by alanines. Although zinc supplementation induces MTF-1 dependent transcription it does not per se enhance dimerization, implying that actual zinc sensing is mediated by another domain. By contrast copper, which on its own activates MTF-1 only weakly in the cell lines tested, stabilizes the dimer by inducing intermolecular disulfide bond formation and synergizes with zinc to boost MTF-1 dependent transcription. PMID- 22057393 TI - Lowest instrumented vertebra selection in Lenke 3C and 6C scoliosis: what if we choose lumbar apical vertebra as distal fusion end? AB - PURPOSE: The aim of this study was to investigate whether or not post-op curve behaviour differs due to different choices of lowest instrumented vertebra (LIV) with reference to lumbar apical vertebra (LAV) in Lenke 3C and 6C scoliosis. METHODS: We reviewed all the AIS cases surgically treated in our institution from 2002 through 2008. Inclusion criteria were as follows: (1) patients with Lenke 3C or 6C scoliosis who were treated with posterior pedicle screw-only constructs; (2) 2-year radiographic follow-up. All the included patients were categorized into three groups based on the relative position of LIV and LAV: Group A-the LIV was above the LAV; Group B-the LIV was at the LAV; Group C-the LIV was below the LAV. All the radiographic parameters were then compared among the groups. All image data were available in our picture archiving and communication systems. Standing anteroposterior (AP) and lateral digital radiographs were reviewed at four times (pre-op, post-op, 3-month and 2-year). In each standing AP radiograph, centre sacral vertical line (CSVL, the vertical line that bisects the proximal sacrum) was first drawn, followed by measuring T1-CSVL, LIV-CSVL, (LIV + 1)-CSVL, LAV-CSVL and thoracic AV-CSVL distance. In addition, the Cobb angles of major thoracic and lumbar curves were measured at the four times and the correction rates were then calculated. RESULTS: Of the 278 patients reviewed, 40 met the inclusion criteria; 11 of these were included in Group A (LIV above LAV), another 11 in Group B (LIV at LAV) and the remaining 18 in Group C (LIV below LAV). At 2 year follow-up, the lumbar vertebrae such as LIV, LIV + 1 and LAV were all more deviated than before surgery in Group A (LIV above LAV), whereas in Group B and C (LIV at and below LAV) they were all less deviated than before surgery. No significant differences were found in thoracic or lumbar correction rate, global coronal balance and incidence rate of trunk shift among the three groups. CONCLUSION: In conclusion, in Lenke 3C and 6C scoliosis, post-op lumbar curve behaviour differs due to different choices of LIV with reference to LAV, that is, the deviation of lumbar curve improves when the LIV is either at or below the LAV but deteriorates when the LIV is above the LAV. Although the greatest correction occurs when the LIV is below the LAV, choosing LAV as LIV can still be the optimal option in certain cases, since it can yield similar correction while preserving more lumbar mobility and growth potential. PMID- 22057394 TI - A multicentric study on validation of spot testing kit. AB - OBJECTIVE: To assess the validity of the Spot testing kit (against the Standard iodometric titration) in the semi-quantitative estimation of iodine in salt. METHODS: The project was conducted at four centers in the country, namely, Vadodara, Jodhpur, Dibrugarh and New Delhi (AIIMS, coordinating centre). Uniform protocol was utilized at all the four centres. The school going children were asked to bring 30 g of iodine from their kitchen in an auto-seal polythene pouche with an identification slip. The iodine content of 3,010 salt samples (more than 700 salt samples from each center) was estimated independently by two different methods i.e., Iodometric Titration (used as reference standard) and Spot Testing Kit (STK) method, and the results were compared. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the STK method in relation to the Standard iodometric titration (SIT) were calculated. RESULTS: From total of 3,010 salt samples, majority (98%) of the salt samples collected were of powdered salt. The specificity of various research centers ranged from 60.5% to 88.9%. The positive predictive value of the various research centers ranged from 69.9% to 98%. The NPV of the various research centers ranged from 96.8% to 100%. The pooled sensitivity and specificity of the STK method (against IT method) for four centers together was 99.6% and 66.7%, respectively. CONCLUSIONS: The STK method is reliable for semi quantitative estimation of iodine content in salt and it can be used for monitoring the quality of iodized salt available in the community. PMID- 22057395 TI - Co-morbidity of Kawasaki disease. AB - Despite more than four decades of investigation, the etiology of Kawasaki disease remains obscure, and none of the proposed etiologic theories for the disease have achieved independent confirmation. Clinical and epidemiologic features support an infectious cause, but the etiology remains unclear. The authors present a case of Kawasaki disease associated with Epstein-Barr virus and Mycoplasma pneumoniae infection in a 3.5-y-old boy. He received two doses of intravenous immunoglobulin due to prolonged course of Kawasaki disease but later had complicated autoimmune haemolytic anaemia. His prolonged fever subsided after azithromycin administration. Epstein-Barr virus infection was confirmed by molecular microbiological pathology of cervical lymph node and serological tests. The serological tests for Mycoplasma pneumoniae also revealed a positive result. Thus, it is concluded that Mycoplasma pneumoniae and Epstein-Barr virus infections may occur simultaneously in a child with Kawasaki disease. In addition, autoimmune hemolytic anaemia may be noted in Kawasaki disease patients after high-dose IVIG administration. To the authors' knowledge, this is the first report of Kawasaki disease with Epstein-Barr virus and Mycoplasma pneumoniae in the English-language literature. PMID- 22057396 TI - Indications and outcome of flexible bronchoscopy in neonates. AB - OBJECTIVE: To analyse the indications, safety and outcome of flexible fiberoptic bronchoscopy (FOB) in neonates. METHODS: This descriptive study was conducted in Level III neonatal unit (ICH, Chennai) and included 84 neonates with various respiratory problems admitted over a 3 y period. RESULTS: The indications included stridor (18%), persistent radiological abnormalities (44%), unexplained wheeze/respiratory distress (21%) and others (17%). The mean age and weight were 25 d and 2.82 kg respectively. Bronchoscopy detected various anomalies like upper airway anomalies (10.7%), lower airway malacia (21%), synchronous airway malacias (19%) and miscellaneous anatomical abnormalities (18%). Bronchoalveolar lavage was done in 62% with microbiological yield in 54% cases.FOB helped in the revision of diagnosis in 57%. Resolution of atelectasis was observed in 13.5% cases. Except for transient hypoxemia in 2 neonates, no other complication was encountered. CONCLUSIONS: Flexible bronchoscopy is safe and useful both as diagnostic and therapeutic tool in neonates with respiratory problems. PMID- 22057397 TI - Use of oscillometric devices for the measurement of blood pressure-comparison with the gold standard. AB - The study was done to validate the use of automated devices (Datascope Duo) as a screening tool for measuring blood pressure. A cross sectional study was conducted in school children from urban slums of Bangalore. Blood pressure was recorded according to standard guidelines using a mercury sphygmomanometer and an automated device (Datascope Duo). The readings obtained using the two instruments were compared. One thousand four hundred eighty nine school children, both males and females, aged 5-16 y were included in the study. Readings with the Datascope Duo varied significantly when compared to the gold standard. The blood pressure measurements using Datascope Duo cannot be recommended as an accurate substitute for manual readings. PMID- 22057398 TI - Detection and identification of species-specific bacteria associated with synanthropic mites. AB - Internal bacterial communities of synanthropic mites Acarus siro, Dermatophagoides farinae, Lepidoglyphus destructor, and Tyrophagus putrescentiae (Acari: Astigmata) were analyzed by culturing and culture-independent approaches from specimens obtained from laboratory colonies. Homogenates of surface sterilized mites were used for cultivation on non-selective agar and DNA extraction. Isolated bacteria were identified by sequencing of the 16S rRNA gene. PCR amplified 16S rRNA genes were analyzed by terminal restriction fragment length polymorphism analysis (T-RFLP) and cloning sequencing. Fluorescence in situ hybridization using universal bacterial probes was used for direct bacterial localization. T-RFLP analysis of 16S rRNA gene revealed distinct species-specific bacterial communities. The results were further confirmed by cloning and sequencing (284 clones). L. destructor and D. farinae showed more diverse communities then A. siro and T. putrescentiae. In the cultivated part of the community, the mean CFUs from four mite species ranged from 5.2 * 10(2) to 1.4 * 10(3) per mite. D. farinae had significantly higher CFUs than the other species. Bacteria were located in the digestive and reproductive tract, parenchymatical tissue, and in bacteriocytes. Among the clones, Bartonella-like bacteria occurring in A. siro and T. putresecentiae represented a distinct group related to Bartonellaceae and to Bartonella-like symbionts of ants. The clones of high similarity to Xenorhabdus cabanillasii were found in L. destructor and D. farinae, and one clone related to Photorhabdus temperata in A. siro. Members of Sphingobacteriales cloned from D. farinae and A. siro clustered with the sequences of "Candidatus Cardinium hertigii" and as a separate novel cluster. PMID- 22057399 TI - Structural requirements for interaction of peroxisomal targeting signal 2 and its receptor PEX7. AB - The import of a subset of peroxisomal matrix proteins is mediated by the peroxisomal targeting signal 2 (PTS2). The results of our sequence and physical property analysis of known PTS2 signals and of a mutational study of the least characterized amino acids of a canonical PTS2 motif indicate that PTS2 forms an amphipathic helix accumulating all conserved residues on one side. Three dimensional structural modeling of the PTS2 receptor PEX7 reveals a groove with an evolutionarily conserved charge distribution complementary to PTS2 signals. Mammalian two-hybrid assays and cross-complementation of a mutation in PTS2 by a compensatory mutation in PEX7 confirm the interaction site. An unstructured linker region separates the PTS2 signal from the core protein. This additional information on PTS2 signals was used to generate a PTS2 prediction algorithm that enabled us to identify novel PTS2 signals within human proteins and to describe KChIP4 as a novel peroxisomal protein. PMID- 22057400 TI - Zoophilia and impulse control disorder in a patient with Parkinson disease. PMID- 22057401 TI - Clinical and MRI patterns of pericallosal artery infarctions: the significance of supplementary motor area lesions. AB - Cerebral infarctions in the anterior cerebral artery (ACA) territory account for only up to 3-5% of strokes. Subject to the affected ACA branches, different clinical patterns can be defined. We report a case series of patients with isolated infarctions of the pericallosal (PC) artery territory. We analyzed 36 consecutive patients presenting over a 10-year period with isolated PC artery territory infarctions (15 left-sided, 19 right-sided, 2 bilateral) regarding clinical symptoms as well as MRI findings. Analysis of DWI lesion pattern showed complete PC artery infarctions in three patients. The majority of patients had partial infarctions predominantly involving either the superior frontal gyrus (n = 12), the corpus callosum (n = 1) or both (n = 20). Hemodynamic lesion patterns were found in 13 patients, while multiple cortical emboli occurred in six. Distal pathology of the ACA (n = 13) was the most frequent MRA finding. Core symptom was contralateral hemiparesis with lower limb predominance (n = 29), partly associated with early-onset spasticity. Interestingly, motor evoked potential recording was abnormal in only five patients. Further characteristic symptoms were psychomotor slowing (n = 9), often with speech disturbances such as decreased verbal fluency, and confusional state (n = 4). Visual or motor hemineglect (n = 5) as well as apraxia (n = 5) was confined to a few patients only. Pericallosal artery infarctions are a rare localization of stroke, mostly occurring as partial infarctions due to distal ACA pathology. Clinically, they are mainly characterized by hemiparesis predominately in the lower limb caused by involvement of supplementary motor cortex areas without affection of the corticospinal tract. PMID- 22057402 TI - Use of intrathecal clonidine in patients with multiple sclerosis or spastic paraparesis. PMID- 22057403 TI - Detection of anti-glutamate receptor epsilon2 and anti-N-methyl-D: -aspartate receptor antibodies in a patient with sporadic Creutzfeldt-Jakob disease. PMID- 22057404 TI - Sporadic juvenile amyotrophic lateral sclerosis caused by mutant FUS/TLS: possible association of mental retardation with this mutation. AB - We present two cases of patients with juvenile amyotrophic lateral sclerosis (ALS), who had no history of familial ALS. The symptoms of both patients started as weakness of the unilateral upper limb and neck, and extended to bulbar and respiratory weakness in a relatively short period. Of note, the first patient was mentally retarded before the onset of weakness. Fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene analyses revealed mutations of p. G492EfsX527 (c. 1475delG), which is a novel deletion/frameshift mutation, in the first patient and p. R514S mutation (c. 1542G > T) in the second patient. Molecular analysis revealed that the mutant FUS/TLS, especially the deletion/frameshift mutation, showed significant cytoplasmic localization in transfected motor neuron-like cells. Our findings suggest the association of mental retardation with the FUS/TLS mutation. Further investigation, including the effect of FUS/TLS on cognitive function, would aid better understanding of FUS/TLS proteinopathies. PMID- 22057405 TI - Transcranial sonography in pantothenate kinase-associated neurodegeneration. AB - After it was reported that increased tissue iron concentrations were associated with increased echogenicity of the substantia nigra (SN) obtained with transcranial sonography (TCS) in animal and postmortem studies, our goal was to use this method in a disorder characterized with iron accumulation in human brain tissue. Therefore, magnetic resonance imaging (MRI) and TCS were conducted in 5 unrelated patients with pantothenate kinase-associated neurodegeneration (PKAN), caused by PANK2 mutations. All patients had an eye of the tiger sign. Hypointense lesions on the T2-weighted MRI images were restricted to the globus pallidus (GP) and SN. TCS also revealed bilateral hyperechogenicity restricted to the LN and SN, with normal DTV values. Both TCS and MRI studies in PKAN patients are in accordance with the pathological findings that accumulation of iron, even in advanced cases, is restricted to the GP and SN, suggesting selective involvement of these structures. PMID- 22057406 TI - The hemodynamic status within 24 h after intravenous thrombolysis predicts infarct growth in acute ischemic stroke. AB - A rapid and complete recanalization of the occluded artery is the ideal goal when intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is administrated to patients with acute ischemic stroke, i.e., limiting the ongoing ischemia to achieve a better outcome. We explored the effect of complete versus partial recanalization of the occluded intracranial artery after IV thrombolysis on the infarct growth and evaluated the functional impact. Using diffusion weighted (DWI) volumetric measurements before rt-PA administration (DWI(1)) and 24 h later (DWI(2)), we calculated the infarct growth in 36 consecutive patients with ischemic stroke treated with IV rt-PA, with the formula DWI(2)/DWI(1). Recanalization of the affected artery was assessed by transcranial Doppler (TCD) and magnetic resonance angiography (MRA) within 24 h of stroke onset. Three patients were eliminated from the analysis; 33 patients were fully analyzed (men: n = 23; mean (SD) age: 72.4 +/- 16 years; time from stroke onset to rt-PA: 179 +/ 54 min; mean NIHSS score at admission: 17). Patients achieving full recanalization by TCD had a smaller infarct growth, compared to those who had a partial or persistent occlusion after thrombolysis: 1.86 versus 2.91 (P = 0.017). This difference was not significant using MRA criteria: 2.01 versus 2.69 (P = 0.193). In the regression analysis, complete recanalization by TCD was an independent predictor of infarct growth (P = 0.045). Thus, complete recanalization measured by TCD within 24 h of IV thrombolysis was independently associated with smaller infarct growth. PMID- 22057407 TI - Factors related to recurrence of paradoxical cerebral embolism due to patent foramen ovale. AB - Patent foramen ovale (PFO) is an important etiology of ischemic stroke in young adults. We investigated factors contributing to recurrent ischemic stroke in patients with PFO. Subjects comprised 47 patients (mean age, 56.8 +/- 14.2 years; range 23-74 years) with ischemic stroke due to PFO who were admitted to our hospital between April 2007 and February 2011. Mean duration of follow-up was 34.5 +/- 13 months. Recurrence occurred in 11 cases. Annual recurrence rate was 23.4%. We investigated relationships between recurrence of ischemic stroke and size of PFO (large, >4 mm; medium, 2-3.9 mm; small, <1.9 mm; absent group), maximal number of microbubbles (determined as the number of microembolic signals: small, 0-5; moderate, 6-25; and multiple, >= 26), massive bubble on contrast transesophageal echocardiography or atrial septal aneurysm, D-dimer level and antithrombotic therapy. Univariate analysis showed size of the PFO (P = 0.013), number of microbubbles (P = 0.021), and presence of a massive bubble on echocardiography (P = 0.04) were related to recurrence of ischemic stroke. Logistic analysis identified size of the PFO (P < 0.05) and massive bubble on echocardiography (P < 0.05) as factors related to recurrence of ischemic stroke. In conclusion, size of the PFO and presence of a massive bubble were considered to be factors associated with recurrence of ischemic stroke due to PFO. PMID- 22057408 TI - A systematic analysis of the theory and practice of syndrome differentiation. AB - Syndrome differentiation is a methodology unique to Chinese medicine. It threads the diagnosis process with clinical treatment into a holistic web of links to determine and regulate the patterns of dysfunctions in the human body. It is seen as the essence of Chinese medicine because it takes into account the theoretical principles, diagnostic methodologies and the modality of treatment holistically. In this process the progressive development and changes of syndromes are also considered by the physician. This paper is a systematic study of the methodology of syndrome differentiation in relation to its clinical applications in the treatment of diseases. To illustrate the efficacy of syndrome differentiation, the relationship between pattern identification and diseases is analysed to provide a guiding principle for integration between Chinese medicine and Western medicine. Diseases being selected include cancer, cardiovascular and metabolic syndromes. A study of renal and hepatic diseases related to lifestyle is also included to highlight the clinical efficacy of syndrome differentiation. The paper also includes an analytical summary of the theoretical advancements made in integrative differentiation methodology during the past five decades which links to the recent clinical thinking and practice. PMID- 22057409 TI - Chinese medicine pattern diagnosis could lead to innovation in medical sciences. AB - Chinese medicine (CM) pattern diagnosis (Bian zheng or syndrome differentiation), as another patient classification approach, has been incorporated with biomedicine diagnosis in clinical practice in China, and the clinical experience has proven that the integration of biomedicine and CM is better in the treatment of many diseases. CM pattern diagnosis is completely different from the diagnosis in biomedicine, and it must take an active role in innovation for medical sciences. This paper is trying to discuss how CM pattern diagnosis lead to innovations in basic research, clinical research and new drug discovery. Scientific basis of CM pattern in innovation of basic research, clinical efficacy and safety, CM pattern based clinical trial design, CM pattern and clinical practice guideline in innovation of clinical study, CM pattern based indication finding, and CM pattern based network pharmacology in innovation of new drug discovery have been discussed. PMID- 22057410 TI - Chinese medicine pattern differentiation and its implications for clinical practice. AB - Chinese medicine practitioners apply the differentiation reasoning for decision making. The wide scope of Chinese medicine intervention provides coverage of methods and techniques with applications to primary, secondary and tertiary levels of prevention. The rapid evolution of mathematical and computational techniques allowed the implementation of several models for pattern differentiation that were tested for several physiologic systems. Concurrently, it is argued that pattern differentiation might improve the efficacy of either traditional or conventional medical interventions. This article reviewed the influence of pattern differentiation into clinical practice organized by medical field: general pattern differentiation; genitourinary (recurrent cystitis); cardiovascular (coronary heart disease; arterial hypertension; angina pectoris); neurology (stroke); surgery; metabolic (diabetes mellitus); hepatic (cirrhosis); gastrointestinal (chronic superficial gastritis); orthopedic (low back pain; rheumatoid arthritis; cervical spondylosis; elbow arthritis); oncology (gastric mucosal dysplasia; lung cancer); gynecologic and obstetric manifestations (nausea and vomiting). The reviewed studies presented achievements that have contributed to the integration of Chinese medicine and evidence-based medicine in the treatment of many mild and severe diseases. Target diseases considered as major public health problems were also investigated and the results are promising regarding the possibility to treat guided by pattern differentiation. PMID- 22057411 TI - An innovative method to accommodate Chinese medicine pattern diagnosis within the framework of evidence-based medical research. AB - Pattern diagnosis is an integral aspect of Chinese medicine (CM). CM differentiates biomedical diseases into patterns, based upon the patient's symptoms and signs. Pattern identification (PI) is used to diagnose, direct the treatment principle and determine the treatment protocol. Most CM research has used fixed formula treatments for Western-defined diseases with outcomes measured using objective biomedical markers. This article presents an innovative method used in a randomised controlled pilot study using acupuncture for participants with hepatitis C virus. Each participant's CM patterns were identified and quantified at baseline which directed the treatment protocol for the treatment group. Data identified that while each participant expressed different patterns at baseline all participants displayed multiple patterns. Six patterns showed some expression by all 16 participants; Liver (Gan) yin vacuity expressing a group aggregate mean percentage of 47.2, binding depression of Liver qi 46.9, and Liver Kidney (Shen) yin vacuity 45.1. Further sub category gender grouping revealed that pattern ranking changed with gender; Liver yin vacuity (male 53.4%, female 51.93%), binding depression of Liver qi (male 50.0%, female 42.86%) and Liver Kidney yin vacuity (male 42.9%, female 47.96%). The quantification of CM patterns described in this article permitted statistical evaluation of presenting CM patterns. Although this methodology is in its infancy it may have potential use in the integration of PI with rigorous evidence based clinical research. Biomedical markers often do not relate to symptom/signs and therefore this innovative measure may offer an additional CM evaluation methodology and further CM PI understanding. PMID- 22057412 TI - Clinical observation of the treatment of myelodysplastic syndrome mainly with Qinghuang Powder. AB - OBJECTIVE: To observe the clinical effectiveness of Qinghuang Powder (QHP) combined with Bupi Yishen Decoction (, BPYS) in treating myelodysplastic syndrome (MDS), and its relationship with France, America, and Britain (FAB) type, international prognosis scaling system (IPSS) risk, and chromosome karyotype. METHODS: There were 124 MDS patients subjected to the tests. By FAB typing, 91 patients were typed as refractory anemia (RA) type and 33 as refractory anemia with excess of blasts (RAEB) type; by IPSS scale, 21 were sorted to low risk, 77 to moderate risk I, 20 to moderate risk II, and 6 to high risk; 78 of them had normal chromosome and 46 with abnormal chromosome, including 26 of trisomy 8. All patients were treated with QHP+BPYS, and the changes of peripheral blood figure and bone marrow were observed. RESULTS: After treatment, the general effective rate was 72.58% (90/124), which in the patients of RA type was 80.22% (73/91) and in RAEB type 51.52% (17/33). The former was better than that in the later (P<0.01). For the analysis in the patients of different IPSS risk degrees, the effective rate was 95.24% (20/21) in the lowrisk group, 72.73% (56/77) in moderate risk I, 65.00% (13/20) in moderate-risk II, and 16.67% (1/6) in high risk group. Those in the first two groups were superior to that in the latter two (P<0.01). The effective rate was 79.49% (61/78) in the patients with normal chromosome and was 60.87% (28/46) in the patients with abnormal chromosome, showing a significant difference between them. While in the patients of trisomy 8, it was 73.08% (19/26), which was parallel to that in the patients with normal chromosome. CONCLUSION: The effectiveness of QHP+BPYS comprehensive therapy for MDS is unquestionably good, and it is markedly correlated with the FAB type and IPSS risk degree of the disease, as well as the normality of chromosome in the patient. PMID- 22057413 TI - Xiongshao capsule promotes angiogenesis of HUVEC via enhancing cell proliferation and up-regulating the expression of bFGF and VEGF. AB - OBJECTIVE: To evaluate the angiogenic effect of the Xiongshao capsule (XSC) in human umbilical vein endothelial cells (HUVEC), and to investigate the possible molecular mechanisms mediating its biological effect. METHODS: Serum pharmacology was applied in this study, in which different doses of XSC were administrated to rats orally and then XSC-containing serum (XSC-S) was collected for the following in vitro experiments. The viability of HUVEC was determined by the 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell density was observed via phase-contrast microscopy. Fluorescence-activated cell sorting analysis with propidium iodide staining was performed to determine cell cycle phase. Cell migration was determined by wound-healing method. Capillary tube formation by HUVEC was examined using ECMatrix gel-based assay. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression levels were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbant assay (ELISA) analyses. RESULTS: XSC-S dose-dependently stimulated proliferation of HUVEC by promoting the cell cycle G1 to S progression. In addition, XSC-S treatment dramatically increased the migration and capillary tube formation of HUVEC in a dose-dependent manner. Moreover, XSC-S enhanced the expression of VEGF and bFGF at both mRNA and protein levels. CONCLUSION: XSC can promote several features of angiogenesis in endothelial cells through up-regulating the expression of bFGF and VEGF, suggesting that XSC may be a potential novel therapeutic agent for the treatment of ischemic heart diseases. PMID- 22057414 TI - Scavenging effect of Naoerkang on amyloid beta-peptide deposition in the hippocampus in a rat model of Alzheimer's disease. AB - OBJECTIVE: To observe the effect of a Chinese medicine compound, Naoerkang (NEK), on amyloid-beta peptide (1-42; Abeta(1-42)) and matrix metalloproteinase-9 (MMP 9) expressions in the hippocampus of Alzheimer's disease (AD) model rats. METHODS: A total of 48 male Sprague Dawley (SD) rats were randomly divided into normal control, untreated, and piracetam groups, and low-dose, medium-dose, and high-dose NEK groups, with 8 rats in each group. The 5-MUL aggregated Abeta(1-42) (2 MUg/MUL) were injected into both CA1 areas of the hippocampus in the rats to establish an AD model, whereas the normal control was treated with the same dose of normal saline. The rats in the NEK groups were treated with a high, medium, or low dose of NEK [60 g/(kg.d), 30 g/(kg.d), and 15 g/(kg.d)], respectively, intragastrically for 28 days; piracetam (0.375 g/kg, intragastrically) was consecutively administered in the piracetam group; and normal saline was applied in the normal control and untreated groups. A Y-maze test was used for behavioral study to test the learning and memory abilities. Abeta(1-42) and MMP-9 expressions in the hippocampus was determined immunohistochemically, and the results were analyzed by image acquisition and an analysis system. RESULTS: Aggregated Abeta(1-42) induced obvious learning and memory dysfunction, as well as up-regulation of Abeta(1-42) expression in the hippocampus. Compared with those in the normal control group, the learning and memory abilities of rats in the untreated group significantly decreased (P<0.01), and the expression of Abeta(1-42) was significantly increased (P<0.01). Twenty-eight days after different treatments, compared with those in the untreated group, the learning and memory abilities of AD model rats in the piracetam, low-dose, medium-dose and high-dose NEK groups were significantly improved (P<0.01 or P<0.05), and the expression of Abeta(1-42) in the hippocampus decreased (P<0.01 or P<0.05), and MMP-9 increased (P<0.01 or P<0.05), especially in the high-dose NEK group. CONCLUSION: NEK might play a role of anti-dementia by increasing the expression of MMP-9 in the hippocampus of AD model rats, resulting in the reduction of the quantity of Abeta(1-42) and improvement in learning and memory ability in AD model rats. PMID- 22057415 TI - Protection of ultra-filtration extract from Danggui Buxue Decoction on oxidative damage in cardiomyocytes of neonatal rats and its mechanism. AB - OBJECTIVE: To investigate whether the administration of the ultra-filtration extract from Danggui Buxue Decoction (EDBD) was able to protect cardiomyocytes from oxidative injury of rats induced by hydrogen peroxide (H(2)O(2)) and its potential mechanism. METHODS: Myocardial cells from 1- to 2-day-old neonatal rats were cultured in Dulbecco's modified Eagle's medium low-glucose and Ham's F12 medium (1:1), and the cellular injury was induced by H(2)O(2). The ultra filtration extract mixture from Angelica sinensis and Hedysarum polybotrys was given in three doses of 3.75, 7.5, and 15 mg/mL. Morphological changes of cardiomyocytes were observed by microscope. Survival rate of myocardial cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cardiomyocyte damages were estimated by detecting lactate dehydrogenase (LDH) and creatine kinase (CK) releases in the medium, superoxide dismutase (SOD) activities, and intracellular malondialdehyde (MDA) and myeloperoxidase (MPO) contents. The levels of caspase-3 and heat shock protein 70 (hsp70) mRNA expression in cardiomyocytes were measured by reverse transcription polymerase chain reaction. RESULTS: The EDBD could protect the cardiomyocytes from H(2)O(2) injury in a dosedependent manner (3.75, 7.50, and 15.00 mg/mL). The EDBD could significantly decrease LDH and CK leakages and intracellular MDA and MPO contents, increase SOD activity, up-regulate hsp70 expression, and down regulate caspase-3 expression. CONCLUSION: The EDBD has protection on cardiomyocytes injured by H(2)O(2) through improving cell antioxidant ability, up regulating hsp70 expression, and inhibiting caspase-3 activity. PMID- 22057416 TI - Chinese ethics review system and Chinese medicine ethical review: past, present, and future. AB - The Chinese medical ethics committee and the ethical review system have made the following achievements: (1) enabled the institutionalization of medical ethics, (2) carried out the ethics review of Chinese medicine (CM) and integrative medicine extensively, (3) trained a large number of ethical professionals, (4) supported and protected the interests of patients and subjects, and (5) ensured the correct direction of biological research and provided ethical defense for the publication of its results. However, at the same time, they are also faced with some new problems and difficulties that need to be resolved in the following ways: (1) to refine the relevant rules of ethical review, (2) to develop the relevant standards of the CM and integrative medicine ethical review, (3) to enhance the independence and authority of ethics committee, (4) to emphasize innovation and to discover and solve new problems, and (5) to increase international exchanges and improve relevant research. PMID- 22057417 TI - 'The necessity must be convincingly shown to exist': standards for compulsory treatment for mental disorder under the Mental Health Act 1983. AB - Current English law has few controls on the involuntary treatment of persons detained under the Mental Health Act 1983. In 2001, R (Wilkinson) v. Broadmoor Special Hospital Authority provided some hope that, in conjunction with the Human Rights Act and the European Convention on Human Rights (ECHR), meaningful substantive and procedural standards for compulsory psychiatric treatment might be developed, but that hope has not been fulfilled. Using Wilkinson and the ECHR jurisprudence as a starting point, this article considers when, if at all, compulsory psychiatric treatment might be justified. In particular, it considers the difference between the 'appropriateness' standard of the English legislation and the ECHR requirement of 'therapeutic necessity', the requirements for appropriate procedure and appropriate legislative clarity, how the courts should deal with disagreements among treating physicians, and the relevance of the capacity and best interests of the detained person. PMID- 22057418 TI - Motor imagery in typing: effects of typing style and action familiarity. AB - The influences of typing style and action familiarity on executed and imagined typing were investigated. A group of touch typists and a group of hunt-and-peck typists were asked to imagine and execute typing texts of different lengths in two different styles: with ten fingers (familiar for touch typists, unfamiliar for hunt-and-peck typists) and with two fingers (unfamiliar for touch typists, familiar for hunt-and-peck typists). The imagination (but not the execution) of familiar and unfamiliar typing was correlated in both groups, indicating that participants used skill knowledge from the familiar action to imagine the unfamiliar action. Only when touch typists imagined familiar typing accurate motor imagery was observed (similar durations of and positive correlations between imagination and execution). When touch typists imagined unfamiliar typing, the average imagination durations resembled the execution durations, but correlations indicated individual differences in the processes of imagination and execution. Hunt-and-peck typists showed shorter imagination than execution durations with both familiar and unfamiliar typing, indicating that in both styles they did not imagine all details of typing. Also, they did not imagine some details specifically related to unfamiliar typing (reflected in particularly high percentages of absolute error). However, correlations indicated that individual difficulties in executing the unfamiliar action were reflected in the imagination durations. In conclusion, skill knowledge from familiar actions is used to imagine unfamiliar actions. Familiarity with actions promotes accurate motor imagery, but only if stable internal action representations have been acquired, and not if action control relies on online, step-by-step control. However, stable internal action representations of familiar actions may be detrimental for imagery of unfamiliar actions. PMID- 22057419 TI - Stenotrophomonas maltophilia in the respiratory tract of medical intensive care unit patients. AB - The purpose of this study was to investigate characteristics of critically ill patients with Stenotrophomonas maltophilia (S. maltophilia) isolated from the respiratory tract, to identify risk factors for S. maltophilia-pneumonia and intensive care unit (ICU) mortality and to analyze antibiotic susceptibility of S. maltophilia. This was a retrospective analysis of 64 medical ICU patients with S. maltophilia in the respiratory tract. Thirty-six patients fulfilled the criteria for diagnosis of pneumonia. A significantly higher lung injury score (LIS) was observed in patients with pneumonia compared to patients with colonization (p=0.010). Independent risk factors for S. maltophilia-pneumonia were higher Sequential Organ Failure Assessment (SOFA) score (p=0.009) and immunosuppression (p=0.014). Patients with S. maltophilia-pneumonia had higher ICU mortality within a 28-day follow-up (p=0.040) and higher hospital mortality (p=0.018) than patients with colonization. The highest antibiotic susceptibility rates were observed to trimethoprim-sulfamethoxazole, tigecycline, and moxifloxacin. Higher SOFA score when S. maltophilia was isolated (p=0.001) and development of renal failure (p=0.021) were independent risk factors for ICU mortality. Higher SOFA score and immunosuppression are independent risk factors for S. maltophilia-pneumonia. Patients with S. maltophilia-pneumonia have a significantly higher ICU mortality within a 28-day follow-up, hospital mortality and LIS compared to patients with S. maltophilia-colonization. PMID- 22057420 TI - Low prevalence of STEC autotransporter contributing to biofilm formation (Sab) in verocytotoxin-producing Escherichia coli isolates of humans and raw meats. AB - Escherichia coli autotransporters (AT) are known to confer adherence to eukaryotic extracellular matrix and may, therefore, be virulence-associated. Recently, the plasmid-borne STEC AT contributing to biofilm formation (Sab) was described in verocytotoxin (VT)-producing E. coli (VTEC) strains that do not carry the locus of enterocyte effacement (LEE). Using polymerase chain reaction (PCR), we investigated the prevalence of sab and other virulence genes, VT1 (vtx1), VT2 (vtx2), intimin (eae), enterohemolysin (ehxA), STEC autoagglutinating adhesin (saa), and subtilase cytotoxin (subA), in VTEC isolates from patients (n=263) and raw meats of ruminants and wildlife (n=104) in Belgium from 1990 to 2010. Overall, sab was detected in three (0.82%) of 367 VTEC strains comprising human isolates of serotypes O162:H28 (no clinical data available) and OX183:H18 (patient with abdominal pain), and one ground beef O181:H16 isolate. These three sab-positive isolates were eae-negative, but ehxA-, saa-, and subA-positive. Our data show that sab is uncommon in VTEC isolates. All sab-positive VTEC strains identified to date carried a comparable plasmid-bound virulence profile (ehxA-saa subA-sab), which may be transmitted to other strains. Sab may mediate intestinal adherence in some LEE-negative VTEC isolates, but more studies on its prevalence and function are needed. PMID- 22057421 TI - Carotid intima-media thickness, thrombin and atherosclerosis. PMID- 22057422 TI - American Indian/Alaska Native willingness to provide biological samples for research purposes. AB - This article examines the willingness of American Indian/Alaska Natives (AI/AN) to provide biological samples for research purposes. Prior cases of abuse and misuse of individuals, materials, and data highlight ethical research concerns. Investigators may be hesitant to engage AI/ANs in research projects. We conducted a survey of AI/ANs in the central plains region of the US over 1 year. This convenience sample completed a series of questions on biological samples and research. Survey results (N=998) indicate that 70.15% of AI/ANs would be willing to provide saliva/spit for a specific study with the proper consent and control of samples. In conclusion, researchers should find ways to work with and for AI/ANs, assuring participant input in the research process. PMID- 22057423 TI - A model program to reduce patient failure to keep scheduled medical appointments. AB - Community health center clinics that rely on scheduled appointments lose revenue and time when patients do not keep their appointments. Various approaches have been used to improve the rate of patient appointments kept. This article provides a model intervention program developed by a quality improvement committee at a Northwest Ohio community health center that is credited with significantly reducing rates of patient failure to keep scheduled medical and dental clinic appointments. The approach of this intervention program is different from others in that it was primarily designed to help patients learn how to become part of the solution to the problem. Community health center staff accomplishes this through engaging patients in a respectful and courteous manner and helping them understand the importance of their involvement in maintaining an efficient scheduling process to benefit all patients. Data collected from outpatient appointment records before and after implementation of the program indicate that missed appointments dropped to less than half the pre-intervention rate. PMID- 22057424 TI - Sugar and dietary fibre composition influence, by different hormonal response, the satiating capacity of a fruit-based and a beta-glucan-enriched beverage. AB - In this study the satiating capacity of three beverages containing 3 g barley beta-glucan, or 2.5 g dietary fibre (DF) from fruit, or without DF (control) was evaluated. Fourteen healthy volunteers were randomized to have isocaloric breakfasts including one of the beverages in different occasions. Appetite ratings over 3 h post-breakfast and energy intakes at ad libitum lunch, blood glucose, insulin, ghrelin, PYY, GLP-1, GIP, and PP concentrations, and 24 h food intake, were assessed. The bevaerages containing DF increased fullness and satiety over 3 h post-breakfast, but only the beta-glucan-enriched vs. the control significantly reduced energy intakes by 18% at lunch and 40% over the rest of the day. Blood ghrelin and PP responses were differently modulated by beverages. The fruit-based and the beta-glucan-enriched beverage suppressed by 8.9% and 8.1% ghrelin response over the 3 h and the first hour post-breakfast, respectively, while only the latter increased PP response by 34.6%, compared to the control. A sucrose-sweetened beverage providing 3 g barley beta-glucans can control food intake by modulating PP response and it can even reduce 24 h energy intake. Ghrelin suppression by fruit dietary fibre and mixed sugars was not sufficient to significantly reduce food intake compared to the control. PMID- 22057425 TI - Detection of the full-length transcript variant for neurokinin-1 receptor in human whole blood associated with enhanced reinforcement of clot by substance-P. AB - We have recently reported that a neurotransmitter for pain, substance-P (SP), promotes platelet-dependent clot formation through neurokinin-1 receptors (NK1Rs), in which leukocytes appear to be involved (J Thromb Thrombolysis 2009;27:280-6). Two naturally occurring splice isoforms of NK1R with different signal transduction potency, namely the full-length and the truncated NK1Rs are identified. It is known that human leukocytes express truncated NK1Rs, while in vivo expression of the full-length NK1R has not yet been fully clarified. Modulatory effects of alternative splicing for NK1Rs on clot formation also remain to be evaluated. Expression of the transcript variant mRNA for NK1Rs in human whole blood (n = 20) was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR). A 15 min time series of the strength of clot, formed after reloading of calcium in citrated whole blood with or without SP (10 nM) and a NK1R antagonist Spantide (1 MUM), was measured by using oscillating probe viscoelastometry. The full-length transcript variant was detected in 5 samples among 20. SP significantly increased the clot strength while Spantide suppressed the SP-derived change. The extent of modulation by SP/NK1R pathway in a subgroup with expression of the full-length transcript variant was three times as potent as those in another subgroup without expression. We conclude that expression of the full-length transcript variant for NK1R can be detected in human whole blood and that such expression is associated with the enhanced reinforcement of clot by SP. Further study is required to nominate this mRNA as a biomarker for prothrombotic risks in painful conditions such as perioperative period. PMID- 22057426 TI - Testicular toxicity of methyl thiophanate in the Italian wall lizard (Podarcis sicula): morphological and molecular evaluation. AB - The effects of the fungicide methyl thiophanate (MT) on testis were determined in the Italian wall lizard (Podarcis sicula) using morphological and molecular analyzes. Three experimental trials were performed: an acute test using six doses, a two-week chronic test, and "ecotoxicological" exposure (3 weeks). The minimal lethal dose (LD(50)) of pure MT, reached by the acute test, was 100 mg/kg body weight. Testicular histopathology of surviving animals showed a reduced lumen and several multinucleated giant cells 24 h after injection followed by large decreases in spermatogonia (72%) and secondary spermatocytes (58%) and a loss of spermatids and sperms 7 days after. In the chronic test, a dose equivalent to 1/100 of LD(50) was injected on alternate days. Complete shutting of the lumen and a great decrease in spermatogonia (82%) were observed. In "ecotoxicological" exposure, achieved with a commercial MT compound, testis showed a decrease in primary spermatocytes (20%) and several vacuoles. An increase in germ cell apoptosis was observed in all experimental groups using TUNEL assay. A decrease in expression of androgen and estrogen receptor (AR and ER) mRNAs was seen in all experimental groups. The reduction in AR and ER mRNAs was correlated to exposure time. Indeed, in the "ecotoxicological" treatment (30 days), the decrease reached 82 and 90% for AR and ER mRNAs, respectively. These data strongly indicate that treatment with MT, damaging the seminiferous epithelium and decreasing steroid receptor expression, might render exposed lizards infertile. PMID- 22057427 TI - Accuracy of the digital anal examination in women with fecal incontinence. AB - INTRODUCTION AND HYPOTHESIS: This study aims to determine the accuracy of digital rectal examination (DRE) to detect anal sphincter defects when compared to endoanal ultrasound (US) in women with fecal incontinence (FI). METHODS: Seventy four patients identified by retrospective chart review who presented with complaints of bothersome FI who underwent endoanal US are the subjects of this analysis. Sensitivity, specificity, and positive and negative likelihood ratios were calculated for the ability of the DRE to detect anal sphincter defects. RESULTS: Anal sphincter defect was suspected on DRE in 75%. At endoanal US, external sphincter defects were noted in all three segments in 41% (complete defect) while partial defects were noted in 30%. DRE demonstrated a sensitivity of 82%, specificity of 32%, +likelihood ratio 1.2 (95% confidence interval (CI), 0.95-1.16) and -likelihood ratio of 0.6 (95% CI, 0.2-1.24) for detecting a complete EAS defect on endoanal US. CONCLUSION: DRE has poor specificity for detecting anal sphincter defects seen on endoanal US. PMID- 22057428 TI - Sulfonamide carbazole receptors for anion recognition. AB - Carbazole-based receptors functionalized with two sulfonamide groups have been synthesized and their properties as anion receptors have been evaluated. The receptor with bis(trifluoromethyl)aniline groups has shown a very high affinity for halide ions, especially remarkable as only two hydrogen bonds are formed in the complexes. (1)H NMR and fluorescence titrations have been carried out and binding constants up to 7.9 * 10(6) M(-1) have been reached. X-ray structures have been obtained and a modelling study has shown the possible reasons for the large affinity of these compounds for halide anions. PMID- 22057429 TI - Review the role of terminal domains during storage and assembly of spider silk proteins. AB - Fibrous proteins in nature fulfill a wide variety of functions in different structures ranging from cellular scaffolds to very resilient structures like tendons and even extra-corporal fibers such as silks in spider webs or silkworm cocoons. Despite their different origins and sequence varieties many of these fibrous proteins share a common building principle: they consist of a large repetitive core domain flanked by relatively small non-repetitive terminal domains. Amongst protein fibers, spider dragline silk shows prominent mechanical properties that exceed those of man-made fibers like Kevlar. Spider silk fibers assemble in a spinning process allowing the transformation from an aqueous solution into a solid fiber within milliseconds. Here, we highlight the role of the non-repetitive terminal domains of spider dragline silk proteins during storage in the gland and initiation of the fiber assembly process. PMID- 22057430 TI - Fast lithium-ion conducting thin-film electrolytes integrated directly on flexible substrates for high-power solid-state batteries. AB - By utilizing an equilibrium processing strategy that enables co-firing of oxides and base metals, a means to integrate the lithium-stable fast lithium-ion conductor lanthanum lithium tantalate directly with a thin copper foil current collector appropriate for a solid-state battery is presented. This resulting thin film electrolyte possesses a room temperature lithium-ion conductivity of 1.5 * 10(-5) S cm(-1) , which has the potential to increase the power of a solid-state battery over current state of the art. PMID- 22057431 TI - Difference of intensity and disparity in impact of climate on several vascular diseases. AB - Several studies have reported the correlation between regional weather patterns and various vascular diseases. However, each vascular disease has inherent characteristics, and the difference of meteorological correlation between these diseases is not well known. This study was aimed at investigating the disparity and intensity of the relationship between meteorological factors and various vascular diseases. A total of 1113 events within 2 years were included in this study. Daily meteorological parameters with and without events were, respectively, compared in acute coronary syndrome (ACS), cerebral infarction (CI), cerebral embolism (CE), cerebral hemorrhage (CH), subarachnoid hemorrhage (SAH), aortic dissection (AD), and aortic aneurysm rupture (AAR). Days with CI onset correlated with fewer sunshine hours, fewer solar radiation factors, greater amounts of precipitation factors, and more humidity factors, whereas CH and CE only showed lower correlation in temperature factors. However, there was no relation seen between ACS, SAH, AD, AAR, and climatic parameters. Our findings suggest that climate affects various cardiovascular and cerebrovascular diseases differently. This finding may help in understanding the mechanism of how vascular events are triggered. PMID- 22057432 TI - Electrogenerated upconverted emission from doped organic nanowires. AB - The electrogenerated upconversion was achieved in the uniformly doped organic nanowires based on triplet energy transfer from tris(2,2'-bipyridyl)ruthenium(II) to 9,10-diphenylanthracene. PMID- 22057433 TI - Laparoscopic splenectomy for immune thrombocytopenia (ITP) patients with platelet counts lower than 1 * 109/L. AB - Laparoscopic splenectomy (LS) has become the gold-standard surgical intervention for the treatment of immune thrombocytopenia (ITP) and the patients who experienced medical relapse to steroid. Fewer series are available regarding LS for patients with an extremely low platelet count. The aim of this study is to investigate the feasibility and safety of laparoscopic splenectomy in the treatment of patients with a preoperative platelet count of less than 1 * 109/L. From April 2006 to Jan 2011, 10 patients were managed by laparoscopic splenectomy for idiopathic thrombocytopenia with an extremely low preoperative platelet count. Preoperative, perioperative, and postoperative medical management has been reviewed. Before laparoscopic splenectomy, all of the 10 patients had a platelet count of less than 1 * 109/L but a normal level of coagulation function. Emergency laparoscopic splenectomy was performed. The mean operating time was 157 min; the mean intraoperative blood loss was 44 mL. During the operations, transfusion was provided in two patients. No intraoperative complications ensued. The patients were followed up for a mean of 28 months and showed good recovery without any postoperative complications. Laparoscopic splenectomy is a feasible technique in the treatment of ITP patients, characterized by severe mucocutaneous bleeding, extremely low platelet count, and normal prothrombin time (PT) and activated partial thromboplastin time (APTT). PMID- 22057434 TI - Interconnected ordered nanoporous networks of colloidal crystals integrated on a microfluidic chip for highly efficient protein concentration. AB - We report a controllable method to fabricate silica colloidal crystals at defined position in microchannel of microuidic devices using simple surface modification. The formed PCs (photonic crystals) in microfluidic channels were stabilized by chemical cross-linking of Si-O-Si bond between neighboring silica beads. The voids among colloids in PCs integrated on microfluidic devices form interconnected nanoporous networks, which show special electroosmotic properties. Due to the "surface-charge induced ion depletion effect" mechanism, FITC-labeled proteins can be efficiently and selectively concentrated in the anodic boundary of the ion depletion zone. Using this device, about 10(3) - to 10(5)-fold protein concentration was achieved within 10 min. The present simple on chip protein concentration device could be a potential sample preparation component in microfluidic systems for practical biochemical assays. PMID- 22057435 TI - Antiplatelet activity of 3-butyl-6-bromo-1(3H)-isobenzofuranone on rat platelet aggregation. AB - This study aimed to explore the impact of 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) on rat platelet aggregation induced by arachidonic acid (AA). Anti platelet activities in vitro and ex vivo in rat platelets and the possible mechanism were also investigated. The 50% inhibitory concentration (IC(50)) of Br NBP was 84 MUM in washed platelet added AA (final concentration, 780 MUM) in vitro, meanwhile intravenous injection of Br-NBP also potently inhibited platelet aggregation ex vivo. Br-NBP significantly restrained thromboxane B(2) formation and Ca(2+) mobilization caused by AA, but failed to regulate 6-keto-prostaglandin F(1alpha) production and malonaldehyde content. Treatment of Br-NBP improved cAMP, cGMP levels and NO synthesis but prevented serotonin secretion and PF(4) release. Results suggested that Br-NBP inhibited rat platelet aggregation and that the anti-platelet activity was related to both arachidonic acid cascade and cGMP-NO signal path. PMID- 22057436 TI - In vitro detection of superoxide anions released from cancer cells based on potassium-doped carbon nanotubes-ionic liquid composite gels. AB - A newly developed electrochemical biosensor for the determination of superoxide anions (O(2)(-)) released from cancer cells using potassium-doped multi-walled carbon nanotubes (KMWNTs)-1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM]PF(6)) ionic liquid composite gels is demonstrated. The KMWNTs-[BMIM]PF(6) can electrocatalyze oxygen reduction to generate a strong current signal in neutral solution. Compared with KMWNTs without [BMIM]PF(6) or MWNTs-[BMIM]PF(6) composites, the KMWNTs-[BMIM]PF(6) can enhance the oxygen reduction peak current by 6.2-fold and 2.8-fold, which greatly increases the detection sensitivity of oxygen. Then, O(2)(-) biosensors are fabricated by mixing superoxide dismutase (SOD) in the KMWNTs-[BMIM]PF(6) gels via monitoring oxygen produced by an enzymic reaction between SOD/O(2)(-) without the help of electron mediators. The resulting biosensors show a linear range from 0.04 to 38 MUM with a high sensitivity of 98.2 MUA mM(-1), and a lower detection limit of 0.024 MUM. The common interferents such as hydrogen peroxide (H(2)O(2)), ascorbic acid (AA), uric acid (UA), and metabolites of neurotransmitters, do not interfere with the detection of O(2)(-). The proposed biosensor is tested to determine O(2)(-) in vitro and from liver cancer and leukemia cells and shows good application potential in biological electrochemistry. PMID- 22057437 TI - Gender- and region-specific variations of estrogen receptor alpha and beta expression in the growth plate of spine and limb during development and adulthood. AB - Although estrogen action is indispensable for normal bone growth in both genders, the roles of estrogen receptors (ERs) in mediating bone growth are not fully understood. The effects of ER inactivation on bone growth are sex and age dependent, and may differ between the axial and appendicular regions. In this study, the spatial and temporal expression of ERalpha and beta in the tibial and spinal growth plates of the female and male rats during postnatal development was examined to explore the possible mechanisms. The level of mRNA was examined and compared with quantitative real-time PCR. The spatial location was determined by immunohistochemical analysis. The 1-, 4-, 7-, 12- and 16-week age stages correspond to early life, puberty and early adulthood after puberty, respectively. Gender- and region-specific differences in ERalpha and beta expression were shown in the growth plates. Mainly nuclear staining of ERalpha and beta immunoreactivity was demonstrated in the spinal and tibial growth plate chondrocytes for both genders. Moreover, our study indicated significant effect of gender on temporal ERalpha and beta expression and of region on temporal ERalpha/ERbeta expression ratio. However, spatial differences of region-related ERalpha and beta expression were not observed. Gender-related spatial changes were detected only at 16 weeks of both spine and limb growth plates. ERalpha and beta immunoreactivity was detected in the resting, proliferative and prehypertrophic chondrocytes in the early life stage and during puberty. After puberty, ERalpha expression was mainly located in the late proliferative and hypertrophic chondrocytes in female, whereas the expression still extended from the resting to hypertrophic chondrocytes in males. Gender- and region-specific expression patterns of ERalpha and beta gene might be one possible reason for differences in sex- and region-related body growth phenotypes. Gender, age and region differences should be taken into consideration when the roles of ERs in the growth plate are investigated. PMID- 22057438 TI - Cell cycle-dependent expression and subcellular localization of fructose 1,6 bisphosphatase. AB - Recently a gluconeogenic enzyme was discovered-fructose 1,6-bisphosphatase (FBPase)-that localizes in the nucleus of a proliferating cell, but its physiological role in this compartment remains unclear. Here, we demonstrate the link between nuclear localization of FBPase and the cell cycle progression. Results of our studies indicate that in human and mouse squamous cell lung cancer, as well as in the HL-1 cardiomyocytes, FBPase nuclear localization correlates with nuclear localization of S and G2 phase cyclins. Additionally, activity and expression of the enzyme depends on cell cycle stages. Identification of FBPase interacting partners with mass spectrometry reveals a set of nuclear proteins involved in cell cycle regulation, mRNA processing and in stabilization of genomic DNA structure. To our knowledge, this is the first experimental evidence that muscle FBPase is involved in cell cycle events. PMID- 22057439 TI - Autoreactivity against myelin basic protein in patients with chronic paraplegia. AB - INTRODUCTION: Previous studies have shown the existence of either cellular or humoral MBP-reactive elements up to 5 years after spinal cord injury (SCI), but not the presence of both after 10 years. MATERIALS AND METHODS: Twelve SCI patients, with more than 10 years of evolution, and 18 healthy blood donors were studied. Lymphocyte proliferation (colorimetric-BrdU ELISA assay) and antibody titers against MBP (ELISA Human IgG MBP-specific assay) were assessed. RESULTS: SCI patients presented a significant T-cell proliferation against MBP (lymphocyte proliferation index: 3.7 +/- 1.5, mean +/- SD) compared to control individuals (0.7 +/- 0.3; P < 0.001). Humoral response analysis yielded a significant difference (P < 0.0001) between the antibody titers of controls and SCI patients. A significant correlation between cellular and humoral responses was observed. Finally, patients with an ASIA B presented the highest immune responses. CONCLUSION: This work demonstrates, for the first time, the existence of both cellular and humoral responses against MBP in the chronic stages (>10 years) of injury. PMID- 22057440 TI - Motor and bladder dysfunctions in patients with vertebral fractures at the thoracolumbar junction. AB - OBJECTIVE: To present the motor deficits and type of neurogenic bladder dysfunction (NBD) in patients with vertebral fractures at thoracolumbar junction. METHODS: Fifty-two patients with single level vertebra fracture over T11-L2 with onset duration of longer than 3 years were enrolled. All participants provided basic demographic data, ambulatory status and received neurologic examination and urodynamic studies. The differences in distribution of NBD types, neurologic injury sites and functional walkers in patients with different levels of vertebral injury were analyzed. Receiver operating characteristic curve analysis was used to define the cutoff value of lower extremities motor score (LEMS) in functional walker and non-walker. RESULTS: Of the 52 patients, the injured levels were 3 (5.8%) in T11, 21 (40.4%) in T12, 22 (42.3%) in L1, and 6 (11.5%) in L2 vertebrae. Eight (15.4%) patients had upper lumbar cord lesions, 26 (50.0%) had epiconus and lumbar roots lesions, 18 (34.6%) had conus medullaris or/and cauda equina lesions. Mean LEMS was 0 +/- 0, 5.4 +/- 7.7, 11.1 +/- 10.2, and 28.0 +/- 11.0 for patients with T11, T12, L1, and L2 fractures, respectively. Patients with L2 fractures had higher LEMS than other levels (p < 0.001). The cutoff value of LEMS for functional walking was set at 20, and both the sensitivity and specificity was 100%. Thirty-one (59.6%) patients had spastic NBD, 18 (35.6%) had flaccid NBD, and 3 (5.8%) had mixed type NBD. Positive prediction value of ankle spasticity for bladder and sphincter spasticity was 95.2 and 100%, respectively. CONCLUSION: Half of the patients had epiconus lesion following thoracolumbar junction fracture, and they had a clinical presentation of flaccid legs and spastic NBD. Patients with L2 fracture had higher LEMS than patients with T11, T12, and L1 fracture. Patients whose LEMS was higher than 20 could all walk functionally. Fracture at the thoracolumbar junction may cause spastic, flaccid, or mixed type NBD, and urodynamic study is an essential tool for the correct diagnosis and management. Ankle spasticity has a high positive predictive value for spastic bladder or sphincter. PMID- 22057441 TI - Introduction to cell culture. AB - The basics of cell culture as applied to human cells are discussed. Biosafety when working with human tissue, which is often pathogenic, is important. The requirements for a tissue culture laboratory are described, particularly the range of equipment needed to carry out cell isolation, purification, and culture. Steps must be taken to maintain aseptic conditions to prevent contamination of cultures with micro-organisms. Basic cell-handling techniques are discussed, including choice of media, primary culture, and cryopreservation of cells so they can be stored for future use. Common assays which are used to determine cell viability and activity are considered. PMID- 22057442 TI - Isolation and cultivation of dermal stem cells that differentiate into functional epidermal melanocytes. AB - Human melanocytes have been extensively studied, but a melanocyte stem cell reservoir in glabrous skin has not yet been found. Human dermis contains cells that are nonpigmented but can differentiate to several different cell types. We have recently shown that multipotent dermal stem cells isolated from human neonatal foreskins are able to differentiate to multiple cell lineages, including pigmented melanocytes. The dermal stem cells grow as three-dimensional spheres in human embryonic stem cell medium and express some neural crest stem cell and embryonic stem cell markers. Melanocytes derived from dermal stem cells express melanocytic markers and act the same way as mature epidermal melanocytes. Dermal spheres, embedded in the reconstructed dermis consisting of collagen with fibroblasts, can migrate to the basement membrane, where they become pigmented in the same way as epidermal melanocytes suggesting that dermal stem cells can give rise to epidermal melanocytes. PMID- 22057443 TI - Isolation, cultivation, and application of human alveolar epithelial cells. AB - The blood-air barrier formed by the alveolar epithelium of the peripheral lung is crucial for the pulmonary delivery of drugs. Most existing in vitro models mimicking the blood-air barrier are represented by tumor cells or immortalized cells and lack biological relevance due to their genetic alterations and underexpressed essential physiological functions. However, the increasing interest of aerosol administration of medicines to the respiratory system requires the development and use of representative in vitro models. Thereby, human alveolar epithelial cells (hAEpC) are a suitable test system allowing standardized toxicity and transport studies for newly developed compounds and delivery systems. The isolation, purification, and cultivation of hAEpC are described as well as their possible application in the so-called Pharmaceutical Aerosol Deposition Device On Cell Cultures (PADDOCC) mimicking the complete inhalation process of a powder aerosol in vitro. PMID- 22057444 TI - Culture of parathyroid cells. AB - The parathyroid cells are highly differentiated with more or less their only function to secrete parathyroid hormone in response to the extracellular calcium level. Tumours from the parathyroid glands are >99% benign, and have a slow proliferation rate. Culture of parathyroid cells is known to be very difficult most likely due to the high differentiation level. This chapter reveals some details in order how to get parathyroid cells to survive in culture after dispersion of normal bovine parathyroid glands or pathological human parathyroid tumours. Detailed protocols describing cell dispersion with collagenase, short term cultures, and establishment of long-term cultures are presented. PMID- 22057445 TI - Functional analysis of human islets of Langerhans maintained in culture. AB - Islets of Langerhans isolated from experimental animals, such as mice and rats, have contributed much to our understanding of the mechanisms by which pancreatic beta-cells secrete insulin in a regulated manner, and this knowledge is important in identifying potential novel therapies for Type 2 diabetes. However, although many of the signal transduction pathways identified in rodent islets are common to humans, some critical differences have been demonstrated experimentally. It is, therefore, essential that experiments are performed using islets isolated from human pancreas to provide robust data defining whether the key observations made in rodents are also applicable to the human situation. The rate-limiting factor in this area of research is the supply of high-quality human islets isolated from pancreases retrieved from organ donors, and the protocols described in this chapter aim to provide methods of maximising information that can be obtained when human islets are maintained in culture. PMID- 22057446 TI - Conversion of non-endocrine human pancreatic cells to insulin-producing cells for treatment of diabetes. AB - Type I diabetes results from the autoimmune destruction of the insulin-secreting pancreatic beta-cells, affecting many millions of people worldwide. The optimal treatment is to restore the endogenous supply of insulin either through the transplantation of pancreas or the transplantation of islets of langerhans or simply the beta-cells. However, the donated pancreas organs are limited and the available organs are only able to treat a small portion of the diabetes patients. Thus, glucose-responsive, insulin-producing cells from human origin are urgently needed. The aim of this chapter is to give some insight views to how to turn the potential human pancreatic non-endocrine cells into cells that are capable of secreting insulin in response to glucose and ameliorating insulin-deficient diabetes conditions after transplantation. PMID- 22057447 TI - Evaluation of cytochrome P450 activities in human hepatocytes in vitro. AB - Major hepatic cytochrome P450 activities (CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) can be simultaneously examined in human hepatocytes by incubation with a cocktail of multiple specific probes. Cocktail strategy in combination with mass spectrometry is shown to be a robust, fast, and sensitive procedure for P450 activity assessment. This procedure allows a drastic reduction of the number of cells required in the assay and sample analysis time and increases throughput and reproducibility. Major applications of the probe cocktail strategy are P450 phenotyping of hepatocytes and induction studies. PMID- 22057448 TI - Human hepatocytes: isolation, culture, and quality procedures. AB - The use of isolated human liver cells in research and development has gained increasing interest during the past years. The possible application may vary between elucidation of new biochemical pathways in liver diseases, drug development, safety issues, and new therapeutic strategies up to direct clinical translation for liver support. However, the isolation of human liver cells requires a well-developed logistic network among surgeons, biologists, and technicians to obtain a high quality of cells. Our laboratories have been involved in various applications of human liver cells and we have long-lasting experiences in human liver cell isolation and their application in R&D. We here summarize the present protocol of our laboratories for cell isolation from normal resected liver tissue, the most common tissue available. In addition, we discuss the necessary network in the clinic and quality controls to maintain human liver cells in culture and the effect of 3D extracellular matrix in cultured cells which results in preservation of hepatocyte epithelial polarity in the form of bile canaliculi and repression of epithelial to mesenchymal transitions occurring in 2D cultures. PMID- 22057449 TI - Preclinical testing of virotherapeutics for primary and secondary tumors of the liver. AB - Virotherapy offers a new treatment strategy using oncolytic viruses as self replicating, tumor-specific agents, which destroy tumors during their natural lytic replication process. To study potential oncolytic viruses, cell culture experiments give basic information about the lytic potential of a virus, measured as cell lysis or decreased viability. For further analysis, animal models are usually employed. As these in vivo experiments are often performed in immunocompromised animals, results have to be interpreted with caution. Therefore, to obtain deeper information of the oncolytic action of specific viruses in a patient's individual context we established a test platform based on human primary tissue slices. In this three-dimensional model, we observed a preferential tumor infection and the penetration of oncolytic measles vaccine virus into deeper cell layers of tumor tissues, which is an essential feature of an effective oncolytic virus. PMID- 22057450 TI - Isolation and functional studies of human fetal gastric epithelium in primary culture. AB - Our understanding of gastric epithelial physiology in man is limited by the absence of normal or appropriate cancer cell lines that could serve as an in vitro model. Research mostly relied on primary culture of gastric epithelial cells of animal species, enriched with surface mucous cells, and devoid of glandular zymogenic chief cells. We successfully applied a new nonenzymatic procedure using Matrisperse Cell Recovery Solution to dissociate the entire epithelium from human fetal stomach. Cultures were generated by seeding multicellular aggregates prepared by mechanical fragmentation. We further demonstrate that this simple and convenient technique allows for the maintenance of heterogenous gastric epithelial primary cultures on plastic without a biological matrix as well as the persistence of viable chief cells able to synthesize and secrete gastric digestive enzymes, i.e., pepsinogen and gastric lipase. In wounding experiments, epithelial restitution occurred in serum-reduced conditions and was modulated by exogenous agents. This culture system is thus representative of the foveolus-gland axis and offers new perspectives to establish the influence of individual growth factors and extracellular matrix components as well as their combinatory effects on gastric epithelium homeostasis. PMID- 22057451 TI - Isolation, characterization, and culture of normal human intestinal crypt and villus cells. AB - The intestinal epithelium is a highly dynamic tissue undergoing constant and rapid renewal. It consists of a functional villus compartment responsible for terminal digestion and nutrient absorption and a progenitor cell compartment located in the crypts that produce new cells. The mechanisms regulating cell proliferation in the crypt, their migration, and differentiation are still incompletely understood. Until recently, normal human intestinal cell models allowing the study of these mechanisms have been lacking. In our laboratory, using fetal human intestines obtained at mid-gestation, we have generated the first normal human intestinal epithelial crypt-like (HIEC) cell line and villus like primary cultures of differentiated enterocytes (PCDE). In this chapter, we provide a detailed description of the methodologies used to generate and characterize these normal intestinal crypt and villus cell models. PMID- 22057452 TI - Primary culture of human renal proximal tubule epithelial cells and interstitial fibroblasts. AB - Renal physiology and pathology are complex systems that are best studied in whole living organisms. This, however, is often restricted by our desire to limit the number of animal experiments undertaken and to replace them with relevant in vitro models that can be used as surrogates for the system under test. Primary culture cells are derived directly from the relevant tissue and therefore correlate more closely with the system under examination. Although the tissue of origin is not always readily available for culture and cells may quickly change their phenotype after only a few passages, they can be used in many circumstances to validate results obtained from closely related cell lines and to confirm vital protein expression patterns. This chapter outlines methods by which proximal tubular epithelial cells and renal interstitial fibroblasts can be isolated and characterized from human renal nephrectomy tissue. PMID- 22057453 TI - Glomerular epithelial and mesangial cell culture and characterization. AB - Culture of isolated kidney glomerular cells has been employed for almost four decades as a tool to dissect pathophysiological effects of individual cell types in renal disease. This chapter aims to highlight in detail the available techniques to isolate, culture, and characterize human glomerular epithelial and mesangial cells. To establish primary culture of these cells, glomeruli are isolated from the cortex of kidney by differential sieving and cellular outgrowths from cultured glomeruli further subcultured in appropriately coated tissue culture plates/flasks. Methods used for characterization of isolated glomerular mesangial and epithelial cells (podocytes) are described as are the phenotypic markers useful for identification. Other sources of isolated glomerular cells such as immortalized cell lines are briefly discussed. PMID- 22057454 TI - Culture of isolated human adipocytes and isolated adipose tissue. AB - Adipose tissue (AT) is no longer considered merely as insulation or padding for human organs. It is an endocrine organ in its own right, which includes composite cells with the ability to differentiate into multiple cell lines. In fact, there is increasing evidence to support the theory that the causation of obesity and its associated metabolic disorders originate at the cellular or tissue level. Adipocyte dysfunction and chronic inflammatory states are able to modulate triglyceride storage and mobilization directly through cytokine and adipokine release. Significant variability exists between adipocyte isolation and culture techniques which subsequently can impact experimental results. We aim to explain the importance of controlling these variables, to assist tailoring methodological choice towards the investigational outcomes, and modifications of the techniques used accordingly. The techniques described in this chapter yield cell and adipose tissue which can be utilised in many different ways, including adipose tissue stem cells for differentiation, DNA analysis, RT-PCR, immunohistochemistry, lipolysis, glucose uptake, and LPL activity. PMID- 22057455 TI - Primary culture of human adipocyte precursor cells: expansion and differentiation. AB - Culture of adipose tissue precursor cells allows gaining insight into the sequential processes involved in adipocyte development. Furthermore, the secretory properties associated with these cellular changes can be studied. Although clonal cell lines are valuable tools for the identification of mechanisms associated with proliferation or differentiation such models do not necessarily represent the complexity of adipose tissue physiology. Primary cell culture systems may be closer to physiology and circumvent some of these restrictions. One advantage is that phenotypic properties of the tissue donor such as gender, age, or body weight are still, at least partially retained in vitro. In primary culture, also differences between various adipose depots can be studied either as a condition per se or in the cellular context of the stromal vascular (SV) fraction. Furthermore, artificial stressors such as hypoxia and other relevant conditions can be applied to elucidate their functional role. Finally, cultures of human adipose precursor cells may also be used as a screening tool for potential novel drug targets to modulate adipocyte differentiation and biology. PMID- 22057456 TI - Primary culture of ovarian cells for research on cell interactions in the hormonal control of steroidogenesis. AB - Ovary is a polymorphic complex structure in which the cells are arranged in two essential endocrine mini glands: the follicle (F) and the corpus luteum (CL). Their secretory function creates an optimal milieu for growth, maturation, and selection of follicles and oocytes competent for ovulation. Monoculture of isolated ovarian cells has identified the secretory potential of the different cell types functioning in this complex gland in vivo. Primary culture of isolated ovarian cells is a good tool for the investigation of cell interactions and its impact on steroidogenesis, dynamics of steroidogenic enzymes, hormone receptors, changes in the cytoskeleton in granulosa cell populations, regulatory mechanisms, and the intracellular pathways of gonadotropin signaling in steroidogenic ovarian cells. Since the granulosa cell number recovered during isolation from the follicle is substantial, this makes primary culture fairly easy and enables many kinds of studies in vitro. Ovarian cells are highly differentiated and express characteristic functional specificity dependent on the dynamics of the sexual cycle. This is important so as not to produce artifacts in vitro. PMID- 22057457 TI - Human vascular smooth muscle cell culture. AB - Human vascular smooth muscle cells (VSMCs) in culture are an important tool in understanding how VSMCs function and contribute to vessel wall contraction as well as disease. In this chapter, we describe methodologies that enable the investigator to culture large numbers of proliferative VSMCs. These VSMCs are heterogeneous and vary in size, shape, and proliferative capacity depending on the disease state and location of the vessel of origin. Therefore, we also describe techniques to validate their identity as bone fide VSMCs. Briefly, the methods include information on how to dissect the blood vessel to remove the medial layer containing VSMCs, as well as methods on how to propagate these cells, by either allowing VSMCs to migrate from the explanted medial tissue or by enzymatically dispersing the cells from the tissue. Both methods are suitable for culturing VSMCs derived from most vessel types with modifications of the enzyme dispersal method suitable for the isolation of microvessel VSMCs. An important feature of VSMCs in culture is that they lose many of their in vivo contractile properties and so model disease-associated VSMCs in the vessel wall rather than a non-proliferative contractile cell. To overcome this limitation, we also describe alternate methods that enable the study of cultured VSMCs in their contractile state by allowing the VSMCs to remain within an intact vessel ring. Overall, these procedures enable the investigator to undertake a diverse array of experimental assays on cultured VSMCs. PMID- 22057458 TI - Culture of human endothelial cells from umbilical veins. AB - The present protocol offers an economical option for the isolation and culture of human endothelial cells for vascular cell biology research due to the non invasive collection procedure being devoid of ethical concerns and ease of the isolation technique, expansion and maintenance under standard cell culture conditions. The human umbilical vein endothelial cell (HUVEC) model is useful for any research on general properties of human endothelium, but as these cells are of foetal and venous origin, other sources could be more appropriate models for studies on specific pathological areas, for example, atherosclerosis or cancer angiogenesis. Nevertheless, HUVEC still represent the most simple and available human vascular cell type widely used in biomedical research. PMID- 22057459 TI - Human peripheral blood mononuclear cell culture for flow cytometric analysis of phosphorylated mitogen-activated protein kinases. AB - Lymphocyte activation and fine tuning of downstream signaling circuits for the regulation of cytokine expression are critical for a successful immune response. Hence, technical protocols permitting simultaneous testing of these attributes in peripheral blood lymphocytes are of paramount importance. Phospho-specific flow cytometry is a novel methodology that detects phosphorylation of signaling effectors in multiple, rare cellular populations within peripheral blood. In addition, it allows the quantification of phosphorylation levels for signaling proteins within each single cell, and therefore is superior compared to traditional biochemical approaches, such as Western blotting. One such important signaling pathway within immune cells is the p38 MAPK pathway involved in the regulation of cytokine expression, cell proliferation and apoptosis. In this chapter, we provide technical instructions for culturing human peripheral blood lymphocytes for simultaneous monitoring of p38 MAPK phosphorylation and associated cytokine expression, especially in rare cell populations, such as NK and NKT. PMID- 22057460 TI - Human CD4+CD25(high)CD127 (low/neg) regulatory T cells. AB - CD4+CD25(high)CD127(low/neg) regulatory T cells (Tregs) play a critical role in the maintenance of peripheral tolerance and in controlling the development of autoimmune diseases. A combination of surface and intracellular markers, namely, CD25, CD39/CD73, CD62L, CD45RO, CD127, glucocorticoid-induced tumor necrosis factor receptor (GITR), CTLA-4, and the forkhead/winged helix transcription factor (FOXP3), has been used to characterize Tregs. Tregs suppress T effector responses mainly in a direct cell-cell contact manner. However, other mechanisms independent from this manner cannot be excluded entirely. It has been shown that Tregs can undergo limited expansion in vitro after the stimulation of TCR in the presence of exogenous cytokines, e.g., IL-2. Expanded Tregs retain their suppression function. Human Tregs have demonstrated their great potential to be used as a therapeutic intervention in preventing graft rejection and treating autoimmune diseases. In this chapter, we have given a review on how to characterize, isolate, expand Tregs and assess their suppressive functions. PMID- 22057461 TI - Human chondrocyte cultures as models of cartilage-specific gene regulation. AB - The human adult articular chondrocyte is a unique cell type that has reached a fully differentiated state as an end point of development. Within the cartilage matrix, chondrocytes are normally quiescent and maintain the matrix constituents in a low-turnover state of equilibrium. Isolated chondrocytes in culture have provided useful models to study cellular responses to alterations in the environment such as those occurring in different forms of arthritis. However, expansion of primary chondrocytes in monolayer culture results in the loss of phenotype, particularly if high cell density is not maintained. This chapter describes strategies for maintaining or restoring differentiated phenotype by culture in suspension, gels, or scaffolds. Techniques for assessing phenotype involving primarily the analysis of synthesis of cartilage-specific matrix proteins as well as the corresponding mRNAs are also described. Approaches for studying gene regulation, including transfection of promoter-driven reporter genes with expression vectors for transcriptional and signaling regulators, chromatin immunoprecipitation, and DNA methylation are also described. PMID- 22057462 TI - Isolation and culture of human osteoblasts. AB - The skeleton is a dynamic organ that is constantly active throughout life. The highly coordinated actions of bone cells early in life determine the body's shape and form, whilst the constant remodelling (bone resorption followed by an equal amount of bone formation) during adulthood helps to maintain skeletal mass and repair microdamage. When the balance of bone resorption and bone formation becomes unequal, bone diseases, such as osteoporosis, occur. In order to develop drugs to combat bone disease, it is important to know the regulatory systems involved in normal bone formation and resorption. In this chapter, we concentrate on bone formation, providing a detailed guide to isolating and culturing primary human osteoblasts in bone explant cultures, as well as the methodology used to characterise and monitor the function of osteoblasts. In combination, these methods provide a powerful tool in bone cell biology and in the development of new novel treatments for bone disease. PMID- 22057463 TI - Human osteoclast culture and phenotypic characterization. AB - Bone remodelling occurs throughout life via the coupled actions of bone resorption and bone formation. When the balance of bone resorption and formation becomes unequal, bone diseases, such as osteoporosis occur, while the absence of functional osteoclasts leads to diseases such as osteopetrosis and pycnodysostosis. In order to develop effective treatments for bone disease the normal regulatory systems involved in bone resorption need to be fully elucidated. The only cell in the body capable of resorbing bone is the osteoclast - a highly specialized cell of haematopoietic origin. Until relatively recently, the ability to study the formation and function of human osteoclasts in vitro has been limited.In this chapter, we provide an up-to-date detailed guide to isolating and culturing primary osteoclasts from human peripheral blood. In addition, we detail the methodology used to characterize osteoclasts and how to quantify resorption in vitro. In combination these methods provide a powerful tool in the study of human osteoclasts and the development of new novel treatments for bone disease. PMID- 22057464 TI - Effects of temperature generated from the Holmium: YAG laser on human osteoblasts in monolayer tissue culture. AB - With the use of lasers for ablation purposes in spinal surgery, the tissue temperature increases above the boiling point of water, leading to tissue ablation by vaporisation. Due to the thermal environment engendered by the use of lasers, there is concern about the safety of the surrounding important structures, such as dura mater, dorsal root ganglia, and nerve roots. PMID- 22057465 TI - Laser microdissection microscopy: application to cell culture. AB - Laser microdissection (LMD) microscopy allows isolation of specific cell populations to target their -molecular profile. There are several different types of LMD microscopes, but they are all based on the same principle. A laser beam is used to cut out cells or tissues of interest from a histological section, cytology preparations, or live cells from tissue cultures. Live cells can be isolated using LMD and processed for downstream molecular work. RNA, DNA, and protein isolation is possible from a small number of cells and the material is suitable for further real-time PCR, ELISA, Western Blotting, and protein microarray analysis. PMID- 22057466 TI - Automated adherent human cell culture (mesenchymal stem cells). AB - Human cell culture processes developed at research laboratory scale need to be translated to large-scale production processes to achieve commercial application to a large market. To allow this transition of scale with consistent process performance and control of costs, it will be necessary to reduce manual processing and increase automation. There are a number of commercially available platforms that will reduce manual process intervention and improve process control for different culture formats. However, in many human cell-based applications, there is currently a need to remain close to the development format, usually adherent culture on cell culture plastic or matrix-coated wells or flasks due to deterioration of cell quality in other environments, such as suspension. This chapter presents an example method for adherent automated human stem cell culture using a specific automated flask handling platform, the CompacT SelecT. PMID- 22057467 TI - Culturing and differentiating human mesenchymal stem cells for biocompatible scaffolds in regenerative medicine. AB - Mesenchymal stem cells from a variety of sites are a natural resource that using appropriate skills can be cultured in the laboratory, in scaffolds, to provide differentiated-cell replacement tissues, for clinical application. To perform such work with human cells, strict ethical integrity must be observed at all stages. Adipocytes, osteocytes and chrondrocytes are amongst the most desirable end-point cells. Hydrolytic degradable scaffolds allow implanted cells to synthesise their own extracellular matrix in situ after implantation, degeneration of the foreign scaffold to temporally match creation of the new innate one. For preliminary in vitro stem cell differentiation protocols, initial investigation is commonly performed with stem cells in commercially available porous collagen sponges or cell-free small intestinal submucosa. Differentiation of stem cells to a specific phenotype is achieved by culturing them in apposite culture media under precise conditions. Once the cells have differentiated, they are checked and characterised in a wide variety of systems. This chapter describes differentiation media for adipocytes, osteocytes, chondrocytes, myocytes and neural precursors and methods of observing their characteristics by microscopy using phase contrast microscopy, standard light microscopy and electron microscopy with tinctorial, immunocytochemical and electron dense stains, respectively. Cell sorting techniques are not dealt with here. Immunocytochemistry/microscopy staining for specific differentiated-cell antigens is an invaluable procedure, and the range of commercially available antibodies is wide. Precautions need to be considered for using actively proliferating cells in vivo, so that implanted cells remain controlled by the body's molecular signals and avoid development of malignancy. PMID- 22057468 TI - Effects of a proximal base on water oxidation and proton reduction catalyzed by geometric isomers of [Ru(tpy)(pynap)(OH2)]2+. AB - Basic difference: The importance of a pendent base in promoting proton-coupled electron-transfer reactions with low activation barriers has been discussed for H(+) reduction or H(2) oxidation in acetonitrile. Investigation of the interaction between a base positioned in the second coordination sphere of a complex and a water ligand in water oxidation reactions using geometric isomers of [Ru(tpy)(pynap)(OH(2))](2+) (see picture) gave intriguing results. PMID- 22057469 TI - Imaging of neonatal brain emergencies: multisequence MRI analysis of pathologic spectrum including diffusion and MR spectroscopy. AB - The purpose of this pictorial essay is to review the normal neonatal brain MR anatomy and the MR imaging appearances of neonatal brain emergencies and discuss the advantages of individual MR imaging sequences and the clinical implications of utilizing MRI as a problem-solving modality in the neonatal intensive care unit. Here we briefly discuss the normal MR imaging anatomy and myelination pattern and normal MR spectroscopy findings in a neonate. The role of individual MR imaging sequences in evaluating various neonatal abnormalities is being emphasized. For example, the utility of diffusion-weighted imaging for the diagnosis of profound hypoxic-ischemic injury and other forms of hypoxic-ischemic encephalopathies and MR spectroscopy in the diagnosis of metabolic encephalopathies and genetic disorders including aminoacidurias is being presented. PMID- 22057470 TI - Analysis of serum and supplemented vitamin C and oxidative stress in HIV-infected children and adolescents. AB - OBJECTIVES: To assess adequacy of vitamin C intake in HIV-infected children and adolescents; to evaluate serum levels of vitamin C and indicators of oxidative stress; to compare with the uninfected group; to correlate serum vitamin C with oxidative stress and associate them according to the reference values. METHODS: Comparative cross-sectional study. Two groups of 27 children and adolescents each, aged between 3 to 19 years. Group 1 (G1) comprised individuals vertically infected with HIV seen at a regional outpatient clinic. Group 2 (G2) comprised invited individuals without history of HIV infection. The groups were matched for age, sex, and socioeconomic status. The following variables were analyzed: body mass index for age; micronutrient intake and consumption; and serum vitamin C, C reactive protein (CRP), and albumin. RESULTS: The mean age was 12 years old. Most subjects were female (17, 63%), and there was prevalence of the economic class C (27, 50%). The most prevalent nutritional status was normal weight in 20 individuals (74.1%) in G1 and 21 (77.8%) in G2. The intake of vitamin C was significantly higher in G1 (p = 0.006; t = 2.987) according to the 24-hour dietary recall method. There were significant differences in serum vitamin C concentration between the groups, with a lower level in G1 (p = 0.000; t = 7.309). In relation to oxidative stress, values of CRP in G1 were significantly higher (p = 0.007; t = 2.958). There was no association between deficiency of vitamin, CRP, and albumin. CONCLUSION: Our findings show that HIV-infected individuals have low levels of vitamin C; however, this deficiency is not related to eating habits, since the intake of this nutrient was higher in this group than in the control group. HIV-infected individuals have specific characteristics that increase their oxidative stress, which is evidenced by increased CRP. PMID- 22057471 TI - Interspecific resource competition-combined effects of radiation and nutrient limitation on two diazotrophic filamentous cyanobacteria. AB - The cyanobacterial blooms in the Baltic Sea are dominated by diazotrophic cyanobacteria, the potentially toxic species Aphanizomenon sp. and the toxic species Nodularia spumigena. The seasonal succession with peaks of Aphanizomenon sp., followed by peaks of N. spumigena, has been explained by the species specific niches of the two species. In a three-factorial outdoor experiment, we tested if nutrient and radiation conditions may impact physiological and biochemical responses of N. spumigena and Aphanizomenon sp. in the presence or absence of the other species. The two nutrient treatments were f/2 medium without NO (3) (-) (-N) and f/2 medium without PO (4) (3-) (-P), and the two ambient radiation treatments were photosynthetic active radiation >395 nm (PAR) and PAR + UV-A + UV-B >295 nm. The study showed that Aphanizomenon sp. was not negatively affected by the presence of N. spumigena and that N. spumigena was better adapted to both N and P limitation in interaction with ultraviolet radiation (UVR, 280 400 nm). In the Baltic Sea, these physical conditions are likely to prevail in the surface water during summer. Interestingly, the specific growth rate of N. spumigena was stimulated by the presence of Aphanizomenon sp. We suggest that the seasonal succession, with peaks of Aphanizomenon sp. followed by peaks of N. spumigena, is a result from species-specific preferences of environmental conditions and/or stimulation by Aphanizomenon sp. rather than an allelopathic effect of N. spumigena. The results from our study, together with a predicted stronger stratification due to effects of climate change in the Baltic Sea with increased temperature and increased precipitation and increased UV-B due to ozone losses, reflect a scenario with a continuing future dominance of the toxic N. spumigena. PMID- 22057472 TI - Pattern analysis and spatial distribution of neurons in culture. AB - The nervous system is a complex, highly-ordered, integrated network of cells. Dispersed cultures of neurons enable investigations into intrinsic cellular functions without the complexities inherent in the intact nervous system. This culture process generates a homogeneously dispersed population that is assumed to be spatially random. Despite the vast number of studies utilizing dispersed neurons, few studies address the spatial distribution of large populations of neurons, in vitro. We used ink-jet printing and surface chemistry to define patterned areas of poly-lysine adhesion (~50 MUm spots) juxtaposed against a fluorinated-silane background. We quantitatively analysed populations of patterned neurons on printed protein spots, and unpatterned neurons. Using a microarray scanner, we acquired large images (72 mm * 22 mm) of patterns, and neurons with and without patterns. Fast Fourier transformation (FFT) image analysis was used to determine global alignment of neurons to patterns. Through point pattern analysis, we described the spatial organization of dispersed neurons with, or without, patterned substrates. Patterned neurons show spatial organization characteristics reminiscent of printed patterns, with spatial distributions representative of unpatterned neurons. Most notably, both patterned and unpatterned neurons show departure from null models of complete spatial randomness (CSR; a homogeneous Poisson process) at shorter distances with conformity to CSR occurring at longer distances. Cellular morphometrics show that when compared to their unpatterned counterparts, spot-patterned neurons exhibit a significant increase (p < 0.0001) in the mean dendritic circularity and an increase in the number of more circular neurons. Through neurite tracing, we show that dendritic processes are also highly confined to patterned areas, and that they are on average 58% shorter than dendrites of neurons without patterns. Our findings show that patterned areas change the spatial organization of the somata and dendrites of cultured neurons, and that traditional neuronal cultures deviate from CSR. PMID- 22057473 TI - Patient outcomes associated with group and individual genetic counseling formats. AB - Identifying new methods to deliver cancer genetic counseling (GC) are needed to meet the growing interest in BRCA1/2 testing. The goal of this pilot feasibility study was designed to test the initial acceptability of group GC on selected patient outcomes (satisfaction, distress, perceived control) in a breast/ovarian cancer genetics clinic setting. Sixty-five participants at increased risk for hereditary breast/ovarian cancer (HBOC) agreed to participate in self-selected individual or group GC appointments. Forty-nine participants completed all study questionnaires and were included in the analyses. There were significant improvements for participants in both the individual and group GC formats with regard to perceived personal control, general psychological distress and cancer specific psychological distress scores. Participants in both the individual and group formats reported high satisfaction scores on the Genetic Counseling Satisfaction Scale. Study results suggest that group GC may be feasible and acceptable to high-risk women. PMID- 22057474 TI - First degree relatives and familial aggregation of gastric cancer: who to choose for control in case-control studies? AB - Gastric carcinogenesis is a multifactorial process involving host gene and environmental interactions. Diverse case-control studies using different types of controls addressed the familial aggregation role for gastric cancer development. Our aim is to discuss the advantages and expected bias according to the different type of eligible controls. A PubMed search of papers on a query on first degree relatives of gastric cancer patients was conducted. The retrieved studies were evaluated regarding quality based on STROBE checklist. Data concerning risk of premalignant lesions and Helicobacter pylori infection was retrieved as the type of controls used on each study. Nine case-control studies were selected. A variety of controls were used ranging from general population to dyspeptic patients and spouses of the cases. We have observed that, independently of the type of control, the risk for the prevalence of premalignant lesions and H. pylori infection was higher for the cases. However, all of the evaluated case control studies were average quality studies (mean 28 out of 45), with a small number of cases and controls (range from 39 to 300). Furthermore, concerning gene environment interaction, each of the discussed type of control (general population, dyspeptic, spouse and neighbor) has potential advantages and disadvantages. The current data suggests that selection of any type of the aforementioned controls is feasible and seems to be mainly related to the feasibility of recruitment more than the genetic or environmental backgrounds. General population and dyspeptic patients would be equally appropriate for studies on familial aggregation of gastric cancer. Nevertheless, high-quality cohort studies are needed to validate this assumption. PMID- 22057475 TI - Facile aromatic radiofluorination of [18F]flumazenil from diaryliodonium salts with evaluation of their stability and selectivity. AB - Aromatic radiofluorination of the diaryliodonium tosylate precursor with [(18)F]fluoride ions has been applied successfully to access [(18)F]flumazenil in high radiochemical yields of 67.2 +/- 2.7% (decay corrected). The stability and reactivity of the diaryliodonium tosylate precursor plays a key role in increasing the production of (18)F-labelled molecules under the fluorine-18 labelling condition. Various conditions were explored for the preparation of [(18)F]flumazenil from different diaryliodonium tosylate precursors. Optimum incorporation of [(18)F]fluoride ions in the 4-methylphenyl-mazenil iodonium tosylate precursor (5f) was achieved at 150 degrees C for 5 min by utilizing 4 mg of the precursor, K(2.2.2)/K(2)CO(3) complex, and the radical scavenger in N,N dimethylformamide. This approach was extended to a viable method for use in automated synthesis with a radiochemical yield of 63.5 +/- 3.2% (decay corrected, n = 26) within 60.0 +/- 1.1 min. [(18)F]Flumazenil was isolated by preparative HPLC after the reaction was conducted under improved conditions and exhibited sufficient specific activity of 370-450 GBq MUmol(-1), with a radiochemical purity of >99%, which will be suitable for human PET studies. PMID- 22057476 TI - Enhanced photoelectrochemical activity of the TiO2 /ITO nanocomposites grown onto single-walled carbon nanotubes at a low temperature by nanocluster deposition. AB - High-resolution transmission electron microscopy (HRTEM) is used to observe a TiO2/ITO-coated composite nanostructure grown onto single-walled carbon nanotubes (SWCNTs). The SWCNTs, indium tin oxide (ITO), and TiO2 mixtures of anatase (A) and rutile (R) are clearly distinguished in the HRTEM images. The thickness of the SWCNT was about 3 nm, and the TiO2 shell included different polycrystalline structures. PMID- 22057477 TI - An unprecedented organic-inorganic hybrid based on the first {Nb10V4O40(OH)2}(12 ) clusters and copper cations. AB - An unprecedented organic-inorganic hybrid {[Cu(6)L(6)(H(2)O)(3)][Nb(10)V(4)O(40)(OH)(2)]}(2).13H(2)O (1) (L = 1,10 phenanthroline) containing the unreported {Nb(10)V(4)O(40)(OH)(2)}(12-) building blocks has been successfully synthesized and its photoluminescent properties, IR spectra, thermogravimetric analyses and single-crystal X-ray diffraction were investigated. PMID- 22057478 TI - Rathke's cleft cysts in children: clinical, diagnostic, and surgical features. PMID- 22057479 TI - Electro-acupuncture therapy in a patient with a total artificial heart. AB - Interaction between the electrical system of implanted cardiovascular devices and electrical stimulation of acupuncture points (electro-acupuncture) can be life threatening. As a result, there is reluctance to use this modality in patients who have been implanted with any cardiac device. A patient with a total artificial heart was successfully treated with electro-acupuncture for inflammatory arthritis without any adverse events. This case illustrates the safety of electro-acupuncture in patients with a total artificial heart. PMID- 22057481 TI - Inhibition of endocytic processes by photodynamic therapy. AB - BACKGROUND AND OBJECTIVES: Recent studies have demonstrated an effect of photodamage on the endocytic pathway involved in recycling of membrane components. Using a series of agents with known sub-cellular targets, we explored the determinants of photodynamic inhibition of endocytic processes in three cell lines: A murine leukemia, a murine hepatoma, and a non-malignant epithelial cell line of human origin. STUDY DESIGN/MATERIALS AND METHODS: The PI-3 kinase antagonist wortmannin blocks endosomal processing pathway dependent on this enzyme, providing an indication of the "flux" of endocytosis. Microscopic observations were used to assess the effect of photodamage on this pathway. Photosensitizing agents specific for mitochondrial, endoplasmic reticulum (ER), lysosomal, and endosomal photodamage were employed. RESULTS: Sub-lethal photodamage directed against endosomes or lysosomes interrupted early steps in this endocytic process in the hepatoma cell line. A mechanism for these effects is proposed. Mitochondrial photodamage could interrupt endocytosis, but at levels that also induced apoptosis. ER photodamage did not affect endocytosis even at lethal levels. Somewhat similar results were obtained with other cell lines, but there were sufficient differences to indicate that the cell phenotype is, in part, a determinant of the endocytic response to PDT. CONCLUSIONS: PDT is therefore seen to have an effect on endocytic processes. Further work will be needed to delineate the role of these endocytic effects in the array of responses to photodynamic therapy. PMID- 22057482 TI - Fluorescence detection and depletion of T47D breast cancer cells from human mononuclear cell-enriched blood preparations by photodynamic treatment: Basic in vitro experiments towards the removal of circulating tumor cells. AB - OBJECTIVES: A major obstacle for permanent cancer eradication is the persistence of circulating tumor cells (CTCs) in blood, which often escape radio- or chemotherapy. Currently no efficient strategy to remove CTCs from peripheral blood in order to lower the risk of metastases or tumor recurrence exists. Photodynamic treatment (PDT) using aminolevulinic acid (ALA) induced protoporphyrin IX (PPIX) as photosensitizer offers an innovative approach to overcome this problem. This study aims at providing basic evidence towards fluorescence detection and photodynamic depletion of scattered cancer cells from blood preparations. METHODS: The breast cancer cell line T47D, endothelial GP8 cells, red blood cells (RBCs) and peripheral blood mononuclear cells (MNCs) have been tested for ALA-induced formation kinetics of PPIX by flow cytometry and microplate fluorescence analysis. The influence of the presence of RBCs on the PPIX-accumulation in cancer cells was evaluated by flow cytometry; the efficacy of PDT on cancer cells and MNCs has been tested by resazurin assay. Mixtures of T47D and GP8 cells and MNCs spiked with cancer cells were tested to determine the limit of fluorescence detection by flow cytometry and antibody co-staining. RESULTS: T47D cells accumulated significantly higher PPIX-amounts after ALA incubation than any other cell type tested. The presence of RBCs had no impact on PPIX-formation in T47D cells. Experiments towards the fluorescence detection of cancer cells in blood revealed that the sensitivity of this method is yet limited. Viability testing after PDT showed that cancer cells where almost completely eradicated after illumination whereas MNCs were almost spared. CONCLUSION: We clearly demonstrate in vitro tumor cell selectivity of PPIX accumulation over endothelial cells, MNCs and RBCs. Breast cancer cells are efficiently killed by PDT with minor depletion of MNCs. Our findings provide a basis for the PDT of blood samples for a future depletion of CTCs. PMID- 22057483 TI - RIP3 expression induces a death profile change in U2OS osteosarcoma cells after 5 ALA-PDT. AB - BACKGROUND AND OBJECTIVE: The receptor-interacting protein 3 (RIP3) has recently been outlined as a key necrosis mediator but is also thought to participate in the regulation of apoptosis. The aim of this study is to compare the cell death profile induced by 5-aminolevulic acid (5-ALA)-mediated photodynamic therapy (PDT) in the RIP3-deficient cell line U2OS and in U2OS cells in which the expression of RIP3 was restored. MATERIALS AND METHODS: RIP3-expressing U2OS cells (RIP3-U2OS) were obtained after transfection and antibiotic selection. Wild type and RIP3-U2OS cells were treated by 5-ALA-PDT. Overall cell viability was evaluated and different parameters characteristic of apoptosis, autophagy, and necrosis were studied. RESULTS: Surprisingly, the survival of RIP3-U2OS cells was higher compared to that of the wild type cells. In addition, RIP3-U2OS cell death was decreased by a zVAD-fmk pre-treatment. A higher cleavage of caspase-3, 7, 8, 9, and PARP was also detected in these cells, pointing out to the activation of caspase-dependent apoptosis. In parallel, a thrust of autophagy was clearly identified in the RIP3-U2OS cells. Conversely, RIP3-U2OS exhibited a lower level of necrosis than the wild types. Interestingly, necrostatin-1 efficiently decreased necrosis level in RIP3-U2OS but not in wild type cells. CONCLUSION: Expression of RIP3 in U2OS cells led to a better survival but also to a death profile change in response to PDT. The apoptotic and autophagic pathways were clearly up-regulated compared to the RIP3-deficient wild type cells. However, induction of necrosis was weaker in the RIP3-U2OS cells. In this context, autophagy is likely to play a protective role against PDT-induced cell death and to allow a better survival of RIP3-U2OS cells. This work also highlights the important role played by RIP3 in the apoptotic pathway, although the modalities are still widely unknown. PMID- 22057484 TI - Verteporfin-based photodynamic therapy overcomes gemcitabine insensitivity in a panel of pancreatic cancer cell lines. AB - BACKGROUND AND OBJECTIVE: Pancreatic cancer is notoriously difficult to treat and resistant to virtually all therapeutics including gemcitabine, the standard front line agent for palliative chemotherapy. Early clinical studies point to a potential role for photodynamic therapy (PDT) in the management of this deadly disease. Here we examine PDT with verteporfin for treatment of cells that are nonresponsive to gemcitabine and identify intracellular and extracellular factors that govern sensitivity to each modality. STUDY DESIGN: Using MTS we assess cytotoxicity of verteporfin-PDT in gemcitabine-treated nonresponsive populations from a panel of five pancreatic cancer cell lines representing a range of tumor histopathology and origin. We conduct Western blots for pro-/anti-apoptotic proteins bax and Bcl-XL to identify factors relevant to PDT and gemcitabine sensitivity. To examine the role of extracellular matrix influences we compare response to each modality in traditional cell culture conditions and cells grown on a laminin-rich basement membrane. RESULTS: All cell lines have gemcitabine nonresponsive populations (17-33%) at doses up to 1 mM while moderate total verteporfin PDT doses (1-6 uM J/cm2) produce nearly complete killing. Our data shows that cells that are nonresponsive to sustained gemcitabine incubation are sensitive to verteporfin PDT indicating that the latter is agnostic to gemcitabine sensitivity. Verteporfin-based PDT decreases Bcl-XL and increases the bax/Bcl-XL ratio toward a pro-apoptotic balance. Insensitivity to gemcitabine is increased in cells that are adherent to basement membrane relative to traditional tissue culture conditions. CONCLUSIONS: Collectively these results indicate the ability of verteporfin-based PDT to bypass intracellular and extracellular cues leading to gemcitabine resistance and point to the emerging role of this therapy for treatment of pancreatic cancer. PMID- 22057485 TI - Role of NF-kappaB/Snail/RKIP loop in the response of tumor cells to photodynamic therapy. AB - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is a therapeutic modality whose efficacy depends on several factors including type of photosensitizer, light fluence and cellular response. Cell recurrence is one of the problems still unsolved in PDT. In this work we found that in B78-H1 murine amelanotic melanoma cells there is a correlation between cell recurrence and the NF-kappaB/Snail/RKIP loop. MATERIALS AND METHODS: Proliferation and migration of surviving cells were analyzed by MTT and wound-scratch assays. The levels of ROS/NO in B78-H1 melanoma cells treated with pheophorbide a (Pba) and light (Pba/PDT) were measured by FACS, while expression of NF-kappaB, Snail and RKIP were determined by Western blots. The mechanism of cell death was investigated by caspase and microscopy assays. RESULTS: Our data show that after a low-dose Pba/PDT treatment, B78-H1 cells are able to recover. This correlates with a low level of NO production, which blocks apoptosis via NF-kappaB pathway. Western blot analyses showed that a low-dose Pba/PDT increases the expression of NF-kappaB and anti-apoptotic Snail, but reduces the expression of pro-apoptotic RKIP. The role played by NF-kappaB in the modulation of Snail and RKIP was investigated using DHMEQ: a NF-kappaB inhibitor which behaves as NO donor. DHMEQ caused a decrease of Snail and an increase of RKIP expression. When B78-H1 cells were treated with a low dose Pba/PDT and DHMEQ, the NO level strongly increased, with the result that Snail was down-regulated and RKIP was upregulated, as observed with a high-dose Pba/PDT. CONCLUSION: One major problem in PDT is the cellular rescue occurring in tissue regions receiving a low-dose PDT. To minimize this problem and sensitize cancer cells to PDT we propose a combined treatment in which the photosensitizer is delivered with a donor of NO acting on the NF-kappaB/Snail/RKIP loop. PMID- 22057486 TI - Molecular determinants of photodynamic therapy for lung cancers. AB - BACKGROUND AND OBJECTIVES: PDT induces apoptosis, inflammatory reactions, immune reactions, and damage to the microvasculature around the tumors. The mechanisms responsible for the anticancer effects of Photofrin-PDT and NPe6-PDT differ somewhat. To select a photosensitizer for lung cancer treatment and to improve the efficacy of PDT, the mechanisms of action for PDT using Photofrin or NPe6 must be elucidated and the phenomena validated by analyzing molecular determinants from clinical samples. STUDY DESIGN/MATERIALS AND METHODS: We examined the role of immunological reactions in the anti-tumor effects of PDT using cytokine-overexpressing cells and investigated whether the anti-apoptotic protein Bcl-2 may be a molecular target. Moreover, we investigated the association between ATP-binding cassette transporter proteins such as breast cancer-resistant protein (BCRP), which can pump out some types of photosensitizer, and the efficacy of PDT using clinical samples from 81 early lung cancer lesions treated with PDT between 1998 and 2006 at the Tokyo Medical University Hospital. RESULTS: Photofrin-PDT damaged Bcl-2 and rapidly induced apoptosis, but NPe6-PDT did not damage Bc-2 nor did it induce morphologically typical apoptosis. However, NPe6-PDT exerted a strong anti-tumor effect, regardless of the overexpression of Bcl-2. By analyzing the BCRP-overexpressing cells, Photofrin, but not NPe6, was found to be a substrate of BCRP. All 81 lung cancer lesions were BCRP-positive; as Photofrin was found to be a substrate of BCRP, the expression of BCRP significantly affected the efficacy of Photofrin PDT. However, NPe6-PDT exerted a strong antitumor effect regardless of BCRP expression, and the complete response rate after NPe6-PDT was much higher than that after Photofrin-PDT. CONCLUSIONS: Our translational research suggests that NPe6-PDT may be superior to Photofrin-PDT for the treatment of lung caner, and individualized approaches to PDT based on the expression status of Bcl-2 and/or BCRP may improve the efficacy of PDT in patients with lung cancers. PMID- 22057487 TI - Photodynamic effects of methylene blue-loaded polymeric nanoparticles on dental plaque bacteria. AB - BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) is increasingly being explored for treatment of oral infections. Here, we investigate the effect of PDT on human dental plaque bacteria in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles with a positive or negative charge and red light at 665 nm. STUDY DESIGN/MATERIALS AND METHODS: Dental plaque samples were obtained from 14 patients with chronic periodontitis. Suspensions of plaque microorganisms from seven patients were sensitized with anionic, cationic PLGA nanoparticles (50 ug/ml equivalent to MB) or free MB (50 ug/ml) for 20 min followed by exposure to red light for 5 min with a power density of 100 mW/cm2 . Polymicrobial oral biofilms, which were developed on blood agar in 96-well plates from dental plaque inocula obtained from seven patients, were also exposed to PDT as above. Following the treatment, survival fractions were calculated by counting the number of colony-forming units. RESULTS: The cationic MB-loaded nanoparticles exhibited greater bacterial phototoxicity in both planktonic and biofilm phase compared to anionic MB-loaded nanoparticles and free MB, but results were not significantly different (P > 0.05). CONCLUSION: Cationic MB-loaded PLGA nanoparticles have the potential to be used as carriers of MB for PDT systems. PMID- 22057488 TI - Vacata- and divacataporphyrin: new photosensitizers for application in photodynamic therapy-an in vitro study. AB - BACKGROUND AND OBJECTIVE: The photodynamic therapy is a well-known method of treatment of both malignant tumors and non-tumor lesions in human patients. In the present study, we aimed at evaluating the in vitro efficacy of the new photosensitizing agents, vacataporphyrin (VP), and divacataporphyrin (DVP). MATERIALS AND METHODS: The effectiveness of VP and DVP was compared to well-known photosensitizers, that is, hematoporphyrin derivative (HPD) and chlorin e6 (Ce6) in identical in vitro conditions. The experiment was performed on a well established breast cancer cell line, MCF-7 and compared to HCV 29T11-2-D1 cell line. Cells were incubated in standard conditions and they were exposed to different concentrations of VP, DVP, HPD, and Ce6, that is, 180, 90, 45, 22.5, and 10 ug/ml. After incubation with photosensitizers, the cells were washed, medium was exchanged and the cells were subjected to irradiation at the proper wavelengths, light intensity (100 mW/sq cm), and total light doses 4.5 and 9 J/sq cm. RESULTS: Our results showed that the VP and DVP are potent photosensitizers and the photocytotoxic effect after the incubation with DVP was much better than that of VP. The cytotoxic effects of VP and DVP were less intensive than these of HPD and Ce6. VP and DVP also accumulated well in the tumor cells. Our results also indicated that the VP and DVP effectiveness on MCF-7 cells was photosensitizer dose and light dose dependent. CONCLUSION: The overall properties revealed by both new porphyrins and particularly a possibility for excitation at a higher wavelength and thus a deeper tissue penetration, make them promising candidates for further in vivo experiments. PMID- 22057489 TI - Amplification of cancer cell apoptosis in photodynamic therapy-treated tumors by adjuvant ceramide analog LCL29. AB - BACKGROUND AND OBJECTIVES: C6-ceramide analog LCL29 was recently shown to improve the cure rates of mouse tumors treated by photodynamic therapy (PDT), but the mechanism underlying the therapeutic gain remains unclear. Since LCL29 is a pro apoptotic agent, the main objective of the present study was to determine how LCL29 affects cancer cell apoptosis in PDT-treated tumors. STUDY DESIGN/MATERIALS AND METHODS: Mice bearing SCCVII tumors (syngeneic squamous cell carcinomas) were treated by PDT with photosensitizer Foscan. Adjuvant LCL29 treatment (40 mg/kg) was 24 hours before PDT. The tumors were excised 3 hours after PDT, disaggregated into single cell suspensions that were stained for flow cytometry to detect apoptosis-related events in cancer cells (caspase activation, loss of mitochondrial transmembrane potential, and intracellular calcium). In addition, phagocytic activity in tumor-associated macrophages was assessed by phalloidin staining. RESULTS: While 5-10% apoptotic cancer cells were found in tumors treated by PDT or LCL29 alone, close to 40% of such cells were found in tumors treated by LCL29 combined with PDT. Mitochondrial depolarization was detected in PDT, LCL29, and LCL29 + PDT groups, reaching similar values in all groups. Intracellular calcium release triggered by PDT was more pronounced when PDT was combined with LCL29. Macrophage phagocytic activity, negatively affected by PDT, was stimulated by adjuvant LCL29. CONCLUSIONS: Combining LCL29 treatment with PDT can enhance intracellular calcium release in cancer cells and strongly amplify their apoptosis. PMID- 22057490 TI - Intracutaneous ALA photodynamic therapy: dose-dependent targeting of skin structures. AB - BACKGROUND: Photodynamic therapy (PDT) using topical aminolevulinic acid (ALA) depends on local drug uptake, metabolism to porphyrins, and depth of light penetration using different wavelengths. Topical ALA-PDT has limited depth of drug penetration. We studied induced porphyrin distribution and PDT after intradermal ALA administration using different drug concentrations followed by high-fluence red light irradiation. MATERIALS AND METHODS: Intradermal injections (~2 mm deep) of ALA concentrations from 0.0005% to 1% were studied in swine to evaluated porphyrin fluorescence before PDT and clinical and histological damage 24 hours after PDT. Porphyrin accumulation was measured by fluorescence microscopy of frozen section. PDT was performed 3 hours after intradermal injections using a 635 nm LED array at a fluence of 200 J/cm2 . Skin responses to PDT were observed grossly and by histology (blind evaluation). RESULTS: Intradermal ALA caused porphyrin accumulation in epidermis, hair follicles (HF), sebaceous glands (SG), sweat glands (eccrine glands, EG and apocrine glands, AG), and subcutaneous fat. Significant differences of fluorescence intensity were observed between different skin structures (P < 0.05), but there was no significant difference comparing HF to SG; epidermis with either HF or SG; and dermis with fat (P > 0.05). Intradermal ALA is potent. ALA concentrations >=0.25% followed by red light exposures caused a very intense vascular PDT reaction. Moderate doses of injected ALA concentration (~0.06%), selectively targeted EG. Low doses (<=0.016%) targeted fat; producing fat necrosis with minimal inflammation, manifested both clinically and histologically. In contrast to topical ALA-PDT, intradermal ALA-PDT can effectively photosensitize deep skin structures. CONCLUSION: Potentially, intradermal ALA-PDT using various ALA concentrations may be useful for treating vascular lesions (malformations, hemangiomas, tumors), EG/AG disorders, fat or deep targets in skin. PMID- 22057491 TI - Tumor response to mTHPC-mediated photodynamic therapy exhibits strong correlation with extracellular release of HSP70. AB - BACKGROUND AND OBJECTIVE: We investigated the relationship among heat shock protein 70 (hsp70) promoter activation, extracellular HSP70 protein levels, and tumor cure in an animal model of meso-tetrahydroxyphenyl chlorin (mTHPC; Foscan(r))-mediated photodynamic therapy (PDT). MATERIALS AND METHODS: Using Western blot analysis, we compared HSP70 protein levels in control and PDT treated EMT6 cells with the amplitude of hsp70-promoter driven green fluorescent protein (GFP) expression in identically treated, stably transfected hsp70 GFP/EMT6 cells. A clonogenic survival assay was performed to assess the relationship among promoter activation, HSP70 levels, and cell survival in vitro. Tumor growth studies with this transfected cell line were performed to examine responses to fluences from 0.1 to 10 J cm(-2) , which ranged from sub-curative to curative. In vivo stereofluorescence and confocal fluorescence imaging were used to assess the temporal kinetics in hsp70 activation in tumors subjected to these fluences and the intratumor spatial correlation between hsp70 induction and extracellular levels of HSP70, respectively. RESULTS: Maximum GFP expression and HSP protein levels in cells were observed at PDT doses that corresponded to 30% cell survival. The relative changes in GFP and HSP70 protein accumulation as analyzed using Western immunoblots agreed very well, thereby confirming the validity of fluorescent reporter assessment of gene expression in our studies. In vivo imaging revealed that hsp70 promoter-driven GFP expression and accumulation of extracellular HSP70 in PDT-treated tumors subjected to non-curative doses exhibit minimal spatial correlation. There is a strong correlation between mTHPC PDT doses that result in long-term tumor cure and those that cause high levels of surface exposed or extracellularly released HSP70s. CONCLUSION: Treatment conditions that induce strong promoter activation do not correspond to tumor cure. PDT doses that result in long-term tumor growth control also produce significant accumulation of extracellular HSP70. PMID- 22057492 TI - Pro-apoptotic and anti-inflammatory properties of the green tea constituent epigallocatechin gallate increase photodynamic therapy responsiveness. AB - BACKGROUND: A polyphenol constituent of green tea, epigallocatechin gallate (EGCG), has anti-carcinogenic properties. A growing number of studies document EGCG-mediated induction of apoptotic pathways and inhibition of pro-survival factors when combined with chemotherapy or radiation. We evaluated the efficacy of EGCG in modulating photofrin (PH)-mediated photodynamic therapy (PDT) responses. METHODS: Mouse mammary carcinoma (BA) cells and transplanted BA tumors growing in C3H mice were treated with PH-mediated PDT. Select groups of treated cells and mice also received EGCG and then cytotoxicity, tumor response, and expression of survival molecules were evaluated in all experimental groups. RESULTS: EGCG increased apoptosis and cytotoxicity in BA cells exposed to PH mediated PDT. The initial pro-survival phase of the unfolded protein response (UPR), characterized by increased expression of the 78 kDa glucose-regulated protein (GRP-78), was induced by PDT. The second pro-apoptotic phase of the UPR, characterized by phospho-c-Jun N-terminal kinase (p-JNK) expression, activation of caspases-3 and 7, poly ADP ribose polymerase (PARP) cleavage, and expression of C/EBP homologous protein was observed when PDT was combined with EGCG. EGCG also decreased the expression of the pro-survival proteins GRP-78 and survivin, and attenuated PDT-induced prostaglandin E2 (PGE2 ) expression in PDT-treated cells. Comparable responses also were observed when BA tumors were treated with PDT and EGCG. In addition, PDT-induced expression of metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) was down-regulated in treated tumor tissue by EGCG. CONCLUSIONS: The polyphenol EGCG improves PDT efficacy by increasing tumor apoptosis and decreasing expression of pro-survival and angiogenic molecules within the tumor microenvironment. PMID- 22057493 TI - Antiangiogenesis agents avastin and erbitux enhance the efficacy of photodynamic therapy in a murine bladder tumor model. AB - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) has been established as an alternative therapy for the treatment of various types of malignant disorders, including oesophageal, lung, and bladder cancer. However, one of the limitations of PDT is treatment-induced hypoxia that triggers angiogenesis. The objective of this study was to evaluate the effects of combination therapy with PDT and an antiangiogenic protocol using monoclonal antibodies against both vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). MATERIALS AND METHODS: In vitro angiogenesis assays and in vivo matrigel assay were performed to understand the inhibitory effects of the antiangiogenic agents. Tumor bearing mice were assigned to six different categories: Control, PDT only, Avastin + Erbitux, PDT + Avastin, PDT + Erbitux, and PDT + Avastin and Erbitux. Treated and control tumors were monitored for recurrence for up to 90 days. RESULTS: In vitro results provided valuable insight into the dynamics of endothelial cells in response to angiogenic stimulants and inhibitors to assess the angiogenesis processes. Addition of VEGF increased the migration of bladder cancer cells and addition of Avastin and Erbitux decreased cell migration significantly. Both inhibitors were also able to suppress invasion and tube formation in human umbilical vein endothelial cells (HUVEC). The in vivo tumor response for PDT with single inhibitor (Avastin or Erbitux) and double inhibitor (Avastin + Erbitux) was comparable; however, targeting both VEGF and EGFR pathways along with PDT resulted in more rapid response. Downregulation of VEGF and EGFR were observed in tumors treated with PDT in combination with Avastin and Erbitux respectively. CONCLUSION: Our results show that blocking the VEGF or EGFR pathway along with PDT can effectively suppress tumor growth and the combination of both VEGF and EGFR inhibitors along with PDT could be used to treat more aggressive tumors to achieve rapid response. PMID- 22057494 TI - Photodynamic therapy of disseminated non-small cell lung carcinoma in a murine model. AB - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) of thoracic malignancies involving the pleural surfaces is an active area of clinical investigation. The present report aims to characterize a model for PDT of disseminated non-small cell lung carcinoma (NSCLC) grown orthotopically in nude mice, and to evaluate the effect of PDT on tumor and normal tissues. STUDY DESIGN: H460 human NSCLC cells were injected percutaneously into the thoracic cavity of nude mice. HPPH PDT (1 mg/kg, 24 hours) was performed via the interstitial delivery (150 mW/cm) of 661 nm light to the thoracic cavity at fluences of 25-200 J/cm. RESULTS: H460 tumors exhibited exponential growth within the thoracic cavity consisting of diffuse, gross nodular disease within 9 days after intrathoracic injection. Tumor volume, measured by magnetic resonance imaging (MRI), was highly correlated with the aggregate tumor mass extracted from the corresponding animal. Intrathoracic PDT at fluences of >=50 J/cm produced significant decreases in tumor burden as compared to untreated controls, however, mortality increased with rising fluence. Accordingly, 50 J/cm was selected for MRI studies to measure intra-animal PDT effects. Tumor distribution favored the ventral (vs. dorsal), caudal (vs. cranial), and right (vs. left) sides of the thoracic cavity by MRI; PDT did not change this spatial pattern despite an overall effect on tumor burden. Histopathology revealed edema and fibrin deposition within the pulmonary interstitium and alveoli of the PDT-treated thoracic cavity, as well as occasional evidence of vascular disruption. Prominent neutrophil infiltration with a concomitant decline in the lymphocyte compartment was also noted in the lung parenchyma within 24 hours after PDT. CONCLUSION: HPPH-PDT of an orthotopic model of disseminated NSCLC is both feasible and effective using intracavitary light delivery. We establish this animal model, together with the treatment and monitoring approaches, as novel and valuable methods for the pre-clinical investigation of intrathoracic PDT of disseminated pleural malignancies. PMID- 22057495 TI - IL-6 potentiates tumor resistance to photodynamic therapy (PDT). AB - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is an anticancer modality approved for the treatment of early disease and palliation of late stage disease. PDT of tumors results in the generation of an acute inflammatory response. The extent and duration of the inflammatory response is dependent upon the PDT regimen employed and is characterized by rapid induction of proinflammatory cytokines, such as IL-6, and activation and mobilization of innate immune cells. The importance of innate immune cells in long-term PDT control of tumor growth has been well defined. In contrast the role of IL-6 in long-term tumor control by PDT is unclear. Previous studies have shown that IL-6 can diminish or have no effect on PDT antitumor efficacy. STUDY DESIGN/MATERIALS AND METHODS: In the current study we used mice deficient for IL-6, Il6(-/-) , to examine the role of IL-6 in activation of antitumor immunity and PDT efficacy by PDT regimens known to enhance antitumor immunity. RESULTS: Our studies have shown that elimination of IL-6 had no effect on innate cell mobilization into the treated tumor bed or tumor draining lymph node (TDLN) and did not affect primary antitumor T-cell activation by PDT. However, IL-6 does appear to negatively regulate the generation of antitumor immune memory and PDT efficacy against murine colon and mammary carcinoma models. The inhibition of PDT efficacy by IL-6 appears also to be related to regulation of Bax protein expression. Increased apoptosis was observed following treatment of tumors in Il6(-/-) mice 24 hours following PDT. CONCLUSIONS: The development of PDT regimens that enhance antitumor immunity has led to proposals for the use of PDT as an adjuvant treatment. However, our results show that the potential for PDT induced expression of IL-6 to enhance tumor survival following PDT must be considered. PMID- 22057496 TI - Novel methods to incorporate photosensitizers into nanocarriers for cancer treatment by photodynamic therapy. AB - OBJECTIVE: A hydrophobic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was loaded into nontoxic biodegradable amine functionalized polyacrylamide (AFPAA) nanoparticles using three different methods (encapsulation, conjugation, and post-loading), forming a stable aqueous dispersion. Each formulation was characterized for physicochemical properties as well as for photodynamic performance so as to determine the most effective nanocarrier formulation containing HPPH for photodynamic therapy (PDT). MATERIALS AND METHODS: HPPH or HPPH-linked acrylamide was added into monomer mixture and polymerized in a microemulsion for encapsulation and conjugation, respectively. For post-loading, HPPH was added to an aqueous suspension of pre-formed nanoparticles. Those nanoparticles were tested for optical characteristics, dye loading, dye leaching, particle size, singlet oxygen production, dark toxicity, in vitro photodynamic cell killing, whole body fluorescence imaging and in vivo PDT. RESULTS: HPPH was successfully encapsulated, conjugated or post-loaded into the AFPAA nanoparticles. The resultant nanoparticles were spherical with a mean diameter of 29 +/- 3 nm. The HPPH remained intact after entrapment and the HPPH leaching out of nanoparticles was negligible for all three formulations. The highest singlet oxygen production was achieved by the post-loaded formulation, which caused the highest phototoxicity in in vitro assays. No dark toxicity was observed. Post-loaded HPPH AFPAA nanoparticles were localized to tumors in a mouse colon carcinoma model, enabling fluorescence imaging, and producing a similar photodynamic tumor response to that of free HPPH in equivalent dose. CONCLUSIONS: Post-loading is the promising method for loading nanoparticles with hydrophobic photosensitizers to achieve effective in vitro and in vivo PDT. PMID- 22057497 TI - Leukocyte-endothelial cell interaction is necessary for photodynamic therapy induced vascular permeabilization. AB - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) affects vascular barrier function and thus increases vessel permeability. This phenomenon may be exploited to facilitate targeted drug delivery and may lead to a new clinical application of photodynamic therapy. Here, we investigate the role of leukocyte recruitment for PDT-induced vascular permeabilization. STUDY DESIGN/MATERIAL AND METHODS: Fluorescein isothiocyanate dextran (FITC-D, 2,000 kDa) was injected intravenously 120 minutes after focal PDT on striated muscle in nude mice bearing dorsal skinfold chambers (Visudyne(r) 800 ug/kg, fluence rate 300 mW/cm2 , light dose of 200 J/cm2). Leukocyte interaction with endothelial cells was inhibited by antibodies functionally blocking adhesion molecules ("MABS-PDT" group, n = 5); control animals had PDT but no antibody injection (group "PDT", n = 7). By intravital microscopy, we monitored leukocyte rolling and sticking in real-time before, 90 and 180 minutes after PDT. The extravasation of FITC-D from striated muscle vessels into the interstitial space was determined in vivo during 45 minutes to assess treatment-induced alterations of vascular permeability. RESULTS: PDT significantly increased the recruitment of leukocytes and enhanced the leakage of FITC-D. Neutralization of adhesion molecules before PDT suppressed the rolling of leukocytes along the venular endothelium and significantly reduced the extravasation of FITC-D as compared to control animals (156 +/- 27 vs. 11 +/- 2 (mean +/- SEM, number of WBC/30 seconds mm vessel circumference; P < 0.05) at 90 minutes after PDT and 194 +/- 21 vs. 14 +/- 4 at 180 minutes after PDT). In contrast, leukocyte sticking was not downregulated by the antibody treatment. CONCLUSION: Leukocyte recruitment plays an essential role in the permeability enhancing effect of PDT. PMID- 22057498 TI - Photodynamic therapy (PDT) using HPPH for the treatment of precancerous lesions associated with Barrett's esophagus. AB - BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) with porfimer sodium, FDA approved to treat premalignant lesions in Barrett's esophagus, causes photosensitivity for 6-8 weeks. HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) shows minimal photosensitization of short duration and promising efficacy in preclinical studies. Here we explore toxicity and optimal drug and light dose with endoscopic HPPH-PDT. We also want to know the efficacy of one time treatment with HPPH-PDT. STUDY DESIGN/MATERIALS AND METHODS: Two nonrandomized dose escalation studies were performed (18 patients each) with biopsy-proven high grade dysplasia or early intramucosal adenocarcinoma of esophagus. HPPH doses ranged from 3 to 6 mg/m2 . At 24 or 48 hours after HPPH administration the lesions received one endoscopic exposure to 150, 175, or 200 J/cm of 665 nm light. RESULTS: Most patients experienced mild to moderate chest pain requiring symptomatic treatment only. Six patients experienced grade 3 and 4 adverse events (16.6%). Three esophageal strictures were treated with dilatation. No clear pattern of dose dependence of toxicities emerged. In the drug dose ranging study (light dose of 150 J/cm at 48 hours), 3 and 4 mg/m2 of HPPH emerged as most effective. In the light dose ranging study (3 or 4 mg/m2 HPPH, light at 24 hours), complete response rates (disappearance of high grade dysplasia and early carcinoma) of 72% were achieved at 1 year, with all patients treated with 3 mg/m2 HPPH plus 175 J/cm and 4 mg/m2 HPPH plus 150 J/cm showing complete responses at 1 year. CONCLUSIONS: HPPH-PDT for precancerous lesions in Barrett's esophagus appears to be safe and showing promising efficacy. Further clinical studies are required to establish the use of HPPH-PDT. PMID- 22057499 TI - Treatment of high grade cervical intraepithelial neoplasia by photodynamic therapy using hexylaminolevulinate may be costeffective compared to conisation procedures due to decreased pregnancy-related morbidity. AB - BACKGROUND AND OBJECTIVES: Standard treatments of high-grade Cervical intraepithelial neoplasia (CIN) are conisation procedures. Theses methods have proven effectiveness but are associated with an increased risk of subsequent pregnancy complications. Recently, photodynamic therapy (PDT) of CIN using hexylaminolevulinate (HAL) may represent an alternative treatment without the risk of cervical insufficiency or scaring. This study aims to evaluate the economical aspect of CIN treatment including associated pregnancy complications by comparing both methods. MATERIALS AND METHODS: We developed model treatment pathways for both conisation procedures and PDT using HAL. Thereafter, we calculated total costs for both treatment pathways including necessary re treatments or alternative treatments. The estimated impact of conisation-related cervical insufficiency, prematurity, perinatal morbidity and life-long disability were determined. The total additional costs per conisation due to perinatal morbidity were calculated. RESULTS: The total cost of treatment for CIN with a conisation procedure alone was 1,473 ?, whereas the PDT procedure alone accounted for 1,386 ?, based of assumptions of a 50% re-PDT rate, a 70% response rate and costs of 500 ? for the PDT intervention itself. We computed 71, 144 and 545 newborns born prematurely due to conisation procedures <28, between 28 and <32 and between 32 and <37 weeks of gestation, leading to 18, 24 and 65 cases of severe, moderate and mild life-long disability. The attributable additional amount of maternofetal morbidity discounted by 3% for 7 years was 573 ? per conisation. The total costs for a conisation therefore added up to 2,046 ?, the total costs per treatment with PDT given the above-mentioned assumptions were 1,558 ?. CONCLUSION: For Germany, PDT has the potential to be a cost-effective treatment for high-grade CIN compared to conisation procedure. Most important, the increased perinatal morbidity, perinatal mortality and associated costs after conisation procedures are significant and may be reduced by the implementation of PDT in CIN treatment. PMID- 22057500 TI - Photochemical internalization of tumor-targeted protein toxins. AB - Photochemical internalization (PCI) is a method for intracellular delivery of hydrophilic macromolecular drugs with intracellular targets as well as other drugs with limited ability to penetrate cellular membranes. Such drugs enter cells by means of endocytosis and are to a large extent degraded by hydrolytic enzymes in the lysosomes unless they possess a mechanism for cytosolic translocation. PCI is based on photodynamic therapy (PDT) specifically targeting the endosomes and lysosomes of the cells, so that the drugs in these vesicles can escape into the cytosol from where they can reach their targets. The preferential retention of the photosensitizer (PS) in tumor tissue in combination with controlled light delivery makes PCI relatively selective for cancer tissue. The tumor specificity of PCI can be further increased by delivery of drugs that selectively target the tumors. Indeed, this has been shown by PCI delivery of several targeted protein toxins. Targeted protein toxins may be regarded as ideal drugs for PCI delivery, and may represent the clinical future for the PCI technology. PMID- 22057501 TI - Liposomal nanostructures for photosensitizer delivery. AB - BACKGROUND AND OBJECTIVE: In photodynamic therapy (PDT), photosensitizers are activated by light of a specific wavelength and produce cytotoxic molecules to damage diseased tissues. Most photosensitizers are hydrophobic and easily aggregate in aqueous solution. To maintain their photodynamic activity and to enhance delivery efficiency of photosensitizers, various pharmaceutical carriers and delivery systems have been investigated for photosensitizers. This review will focus on liposomal nanostructures for the delivery of photosensitizing agents. METHODS: The published literature of liposomal structures, formulations, and pharmaceutical applications for photosensitizer delivery was reviewed with the main focus on articles published between 2004 and 2011 after the two excellent reviews by Derycke et al., Adv Drug Deliv Rev 2004:56(1); 17-30 and Chen et al., Expert Opin Drug Deliv 2005:2(3);477-487. Many articles dating back to 1970s were also covered for the purpose of obtaining information about historoical development of liposomal formulations for photosensitizer delivery. The systematic search was performed using several electronic databases, including Pubmed and Medline with the key search terms including PDT, photosensitizer, liposome, nanoparticle, formulation, biodistribution, etc. RESULTS: This review focuses on liposomal nanostructures with an in depth discussion on the liposomal structure, size-related effect on blood circulation and composition of phospholipids. Different active targeting strategies will also be reviewed which serve to improve specific targeting of photosensitizers to diseased tissue. To further enhance the selective release and accumulation of photosensitizers at the targeted tissue, triggered release methods have been developed. Many other liposomal structure-based nanoparticles have been developed for improved delivery efficiency for topical and systemic administration of pharmaceutics. Finally, a new class of phototransducing liposomes called "porphysomes" will also be introduced, which achieves intrinsic multifunctionality together with structure simplicity. CONCLUSION: Liposomes have been proved to be efficient and safe organic carriers for photosensitizers. Multifunctional liposomal formulations, such as porphysome, are further explored for clinic theranostic applications. PMID- 22057502 TI - New aspects of photodynamic therapy for central type early stage lung cancer. AB - BACKGROUND: and Objective Photodynamic therapy (PDT) has come to be considered as the first choice of treatment for central type early stage lung cancer (CELC). Recent advances in the ability to diagnose CELC, and in photosensitizers, as well as sophisticated clinical management, may improve the therapeutic outcome and expand the indications of PDT. MATERIALS AND METHODS: We made the search for papers on PDT for lung cancer to select the most relevant articles. Based on this review and our recent data, we discussed the best available evidence for the diagnosis, the definition of indications, photosensitizers, and clinical management with regard to PDT. RESULTS: To obtain complete response (CR) by PDT, the selection of the indications is extremely important, including the extent of the tumor on the bronchial surface and the depth of invasion in the bronchial wall. The development of autofluorescence bronchoscopy (AFB) and endobronchial ultrasonography (EBUS) have had a large impact on diagnostic bronchoscopy for CELC. CELCs less than 1 cm in diameter showed a favorable cure rate by PDT, thus this is a good indication for PDT. The relatively newer photosensitizer NPe6, which has a stronger antitumor effect than Photofrin, showed similar treatment outcome even for large tumors >1.0 cm in diameter. Furthermore, comprehensive management including photodynamic diagnosis before and after PDT should be effective to minimize the possibility of local recurrence after PDT. CONCLUSION: The present guidelines of PDT for CELC were established based on the data obtained from studies in the 1980's. We postulate that comprehensive diagnosis and the new generation of photosensitizers may increase the CR rate and expand the indications of PDT for larger tumors. PMID- 22057504 TI - Photodynamic therapy for prostate cancer--an emerging approach for organ-confined disease. AB - Since the first report of the use of photodynamic therapy (PDT) for prostate cancer in 1990 it has been investigated as a primary and a salvage treatment, using either whole gland or focal approaches. Since 1990 advances in the transperineal approach to the prostate, coupled with photosensitizers which have a short drug-light interval and minimal skin phototoxicity, have resulted in major advances in the field. This review will look at the work done to date, and the ongoing studies which help to define the place of PDT as a useful treatment modality for organ-confined prostate cancer. PMID- 22057503 TI - Photodynamic therapy for infections: clinical applications. AB - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) was discovered over 100 years ago by its ability to kill various microorganisms when the appropriate dye and light were combined in the presence of oxygen. However it is only in relatively recent times that PDT has been studied as a treatment for various types of localized infections. This resurgence of interest has been partly motivated by the alarming increase in drug resistance amongst bacteria and other pathogens. This review will focus on the clinical applications of antimicrobial PDT. STUDY DESIGN/MATERIALS AND METHODS: The published peer-reviewed literature was reviewed between 1960 and 2011. RESULTS: The basics of antimicrobial PDT are discussed. Clinical applications of antimicrobial PDT to localized viral infections caused by herpes and papilloma viruses, and nonviral dermatological infections such as acne and other yeast, fungal and bacterial skin infections are covered. PDT has been used to treat bacterial infections in brain abscesses and non-healing ulcers. PDT for dental infections including periodontitis and endodontics has been well studied. PDT has also been used for cutaneous Leishmaniasis. Clinical trials of PDT and blue light alone therapy for gastric Helicobacter pylori infection are also covered. CONCLUSION: As yet clinical PDT for infections has been mainly in the field of dermatology using 5-aminolevulanic acid and in dentistry using phenothiazinium dyes. We expect more to see applications of PDT to more challenging infections using advanced antimicrobial photosensitizers targeted to microbial cells in the years to come. PMID- 22057505 TI - Photodynamic therapy for cholangiocarcinoma. AB - The only hope for cure in patients with cholangiocarcinoma is curative surgical resection. Unfortunately it can only performed in less than half of the patients. In the palliative setting endoprostheses insertion improves cholestasis. Survival time is not prolonged. The most promising conventional antitumoral therapy is chemotherapy with cisplatin and gemcitabine. However, randomized trials showing a clear survival advantage of chemo- or radiotherapy are missing. Photodynamic therapy utilizing photo-physical properties of light-absorbing drugs to efficiently generate reactive cytotoxic oxygen species has shown efficacy in several pilot studies, retrospective comparative studies and two prospective, randomized studies. Here, we review mechanism of action, technique, and efficacy of photodynamic therapy for cholangiocarcinoma. PMID- 22057506 TI - Feasibility of Pisum sativum as an expression system for pharmaceuticals. AB - Based on its high protein content and excellent storage capacity, pea (Pisum sativum), as well as other plants, is considered to be a suitable production platform for protein-based pharmaceuticals. Its capacity to produce high proportions of active recombinant proteins (up to 2% total soluble protein corresponding to approximately 8 mg/g fresh weight) has been proven using pea derived strong seed-specific promoters. The active antigens produced were also stable for more than 4 years. Pea can be used as a feed additive, up to a proportion of 30% to total feed, despite the presence of lectins. Thus, a low dosage of recombinant pea-based pharmaceuticals is non-hazardous. In addition, it is independent of N-fertilisation, has excellent biosafety characteristics and is accessible to gene transfer. Growth systems with a capacity for high yield are available for the greenhouse (5 t/ha) and, to a limited extent, also in the field (2.3 t/ha). The practicable establishment of pea seed banks allows a continuous production process. Although the use of a pea system is limited by complex transformation procedures, these advantages render pea a promising plant for the production of pharmaceuticals. PMID- 22057507 TI - Effects of induced fatigue on brain activity during sensorimotor control. AB - The aim of this study was to study if accuracy in sensorimotor control and cortical activity was influenced after induced fatigue during a knee joint reproduction task. Twelve volunteers performed a sensorimotor task before, directly after and 60 min after a prolonged exhaustive exercise protocol. The task consisted of an active reproduction of a target knee angle. After three practice trials, visual feedback was taken and the task was performed for 10 repetitions at a suitable pace. Reproduction accuracy was analyzed and EEG raw data were obtained from the frontal, central, temporal, parietal and occipital scalp locations during the task. The average power spectra in theta and alpha frequencies were computed across conditions for each participant. Task accuracy decreases significantly related to fatigue and increases after recovery. This is accompanied by a significant decrease in frontal theta, alpha-1 and alpha-2 frequencies after inducing fatigue. The power values in all frequency bands recovered after 60 min. Sensorimotor control was influenced by induced fatigue, which could be demonstrated in behavior and brain activity. Characteristics of brain activity demonstrated an increase in theta and a decrease in alpha-1 and alpha-2 frequency band power. The changes were discussed related to attentional recourses, alertness and somatosensory information processing mechanisms. PMID- 22057508 TI - Cold water immersion recovery following intermittent-sprint exercise in the heat. AB - This study examined the effects of cold water immersion (CWI) on recovery of neuromuscular function following simulated team-sport exercise in the heat. Ten male team-sport athletes performed two sessions of a 2 * 30-min intermittent sprint exercise (ISE) in 32 degrees C and 52% humidity, followed by a 20-min CWI intervention or passive recovery (CONT) in a randomized, crossover design. The ISE involved a 15-m sprint every minute separated by bouts of hard running, jogging and walking. Voluntary and evoked neuromuscular function, ratings of perceived muscle soreness (MS) and blood markers for muscle damage were measured pre- and post-exercise, immediately post-recovery, 2-h and 24-h post-recovery. Measures of core temperature (Tcore), heart rate (HR), capillary blood and perceptions of exertion, thermal strain and thirst were also recorded at the aforementioned time points. Post-exercise maximal voluntary contraction (MVC) and activation (VA) were reduced in both conditions and remained below pre-exercise values for the 24-h recovery (P < 0.05). Increased blood markers of muscle damage were observed post-exercise in both conditions and remained elevated for the 24-h recovery period (P < 0.05). Comparative to CONT, the post-recovery rate of reduction in Tcore, HR and MS was enhanced with CWI whilst increasing MVC and VA (P < 0.05). In contrast, 24-h post-recovery MVC and activation were significantly higher in CONT compared to CWI (P = 0.05). Following exercise in the heat, CWI accelerated the reduction in thermal and cardiovascular load, and improved MVC alongside increased central activation immediately and 2-h post-recovery. However, despite improved acute recovery CWI resulted in an attenuated MVC 24-h post-recovery. PMID- 22057509 TI - Successful treatment of lymphoid blastic crisis in chronic myelogenous leukemia with the additional bcr/abl transcript using imatinib-combined chemotherapy and high-dose chemotherapy with allogeneic bone marrow stem cell transplantation. AB - Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome. Although the major BCR/ABL transcript is present in majority of CML patients, the minor BCR/ABL transcript is rarely reported as an additional chromosomal abnormality related to the progression of CML. We describe the case of a 37-year-old woman who had CML and pain in the extremities. She was diagnosed with lymphoid blast crisis of CML on the basis of the following findings: presence of promyelocytes, myelocytes, and metamyelocytes in peripheral blood smear; detection of major and minor BCR/ABL transcripts by polymerase chain reaction analysis; proliferation of lymphoblastic cells with abnormal B-cell phenotype; and aberrant expression of myeloid antigens in the bone marrow. The patient underwent one course of idarubicin and cytosine arabinose therapy combined with imatinib followed by daunorubicin/cyclophosphamide plus vincristine and prednisone/L: -asparaginase (DNR/COP/L: -ASP) therapy, high-dose cytosine arabinose, and CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone). Subsequently, the patient underwent high-dose chemotherapy (total body irradiation and cyclophosphamide) followed by allogeneic bone marrow stem cell transplantation from a human leukocyte antigen (HLA)-matched unrelated donor. After these treatments, the patient was disease-free for 19 months. Our case suggests that these treatments may be feasible, safe, and effective for the treatment of patients with blast crisis CML expressing the minor BCR/ABL transcript. PMID- 22057510 TI - Symptomatic severe hypertriglyceridaemia with asparaginase therapy in acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma: is rechallenging safe? AB - Severe hyperlipidaemia with asparaginase therapy is rare. We report six cases, four of which developed significant problems with severe hyperlipidaemia during induction therapy for ALL and lymphoblastic lymphoma. The median triglyceride level was 22.3 mmol/L and the median cholesterol level was 12.3 mmol/L. None of the patients showed signs or symptoms of pancreatitis. Three children were re exposed with Peg asparaginase, and one with Erwinia asparaginase, without recurrence of hyperlipidaemia or other symptoms. These cases highlight the dilemma in managing such rare cases of symptomatic hypertriglyceridaemia secondary to asparaginase and steroid therapy. PMID- 22057511 TI - Synaptic protein expression is regulated by a pro-oxidant diet in APPxPS1 mice. AB - Dietary factors may play a role in Alzheimer's disease (AD) pathogenesis. In an effort to recapitulate some of the synaptic protein changes observed in the disease, AD transgenic and wild-type mice were fed either a normal or pro-oxidant diet for 3 months from three months of age. Pro-oxidant diet treatment resulted in altered expression of vesicular glutamate transporter-1 and glutamine synthetase, suggesting changes in glutamatergic synaptic function, and increased expression of urokinase plasminogen activator receptor, possibly reflecting oxidative stress. PMID- 22057512 TI - A new year--a new outlook. PMID- 22057514 TI - Recent advances and future challenges in glycan microarray technology. AB - Glycan microarrays, carrying hundreds of different sugars on chip surfaces, have become a standard tool for the study of interactions of biomolecules with carbohydrates. The chip-based format offers important advantages, including the ability to screen in parallel several thousand binding events on a single slide, the minimal amount of sample required for one experiment, and the multivalent display of sugars on the chip that mimics the presentation of carbohydrates in nature. This chapter presents recent advances and future challenges in glycan microarray technology. We describe different immobilization and detection methods as well as applications in glycomics, drug discovery, and biomedicine. PMID- 22057515 TI - Chemical synthesis of carbohydrates and their surface immobilization: a brief introduction. AB - For all carbohydrate microarrays, two important prerequisites are necessary: the carbohydrate of interest has to be obtained either by isolation from natural sources, enzymatic or chemical synthesis; an immobilization of the carbohydrate at the surface of the chip has to be achieved. This chapter provides a very brief overview of the chemical synthesis of carbohydrates (creation of building blocks, assembly, and deprotection) and of immobilization techniques. Numerous methods are known to construct oligosaccharides by chemical methods. A typical monosaccharide building block, used in oligosaccharide assembly, is equipped with different protecting groups that mask the hydroxyl and amine groups. In general, a good leaving group at the anomeric center that can easily be activated is mandatory; especially trichloroacetimidates, phosphates, and thioethers have been widely used for the creation of glycosidic bonds. After the complete assembly of the oligosaccharide, a global deprotection of all permanent protecting groups affords the desired target structure with free hydroxyl groups. Linkers, which were introduced during the synthesis, must often be modified at the end to create appropriate functionalities for surface immobilization. PMID- 22057516 TI - General consideration on sialic acid chemistry. AB - Sialic acids, also known as neuraminic acids, are a family of negatively charged alpha-keto acids with a nine-carbon backbone. These unique sugars have been found at the termini of many glycan chains of vertebrate cell surface, which play pivotal roles in mediating or modulating a variety of physiological and pathological processes. This brief review covers general approaches for synthesizing sialic acid containing structures. Recently developed synthetic methods along with structural diversities and biological functions of sialic acid are discussed. PMID- 22057517 TI - Synthesis of azido-functionalized carbohydrates for the design of glycoconjugates. AB - As carbohydrates play a major role in numerous biological processes through their interactions with lectins and also appear as one of the most crucial post translational modifications of proteins, chemists have developed several approaches for the design of glycoconjugates based on a series of conjugation methodologies. The recent development of copper(I)-catalyzed azide-alkyne cycloaddition (CuACC) paved the way to a novel conjugation strategy in which azido-functionalized carbohydrate derivatives can be readily connected to alkyne functionalized (bio)molecules. This so-called "click chemistry" methodology has now found numerous applications both in chemistry and biology. The azido moiety can be introduced either directly at the anomeric carbon of the carbohydrate derivative, or attached to a spacer arm. We describe here the syntheses of 2,3,4,6-tetra-O-acetyl-beta-D: -glucopyranosyl azide as well as 1-azido-3,6 dioxaoct-8-yl 2,3,4,6-tetra-O-acetyl-beta-D: -galactopyranoside and 1-azido-3,6 dioxaoct-8-yl 2,3,6,2',3',4',6'-hepta-O-acetyl-beta-D: -lactoside. These molecules can then be used in the construction of glycoconjugates to find applications in chemical biology. PMID- 22057518 TI - Polypyrrole-oligosaccharide microarray for the measurement of biomolecular interactions by surface plasmon resonance imaging. AB - The polypyrrole approach initially developed for the construction of DNA chips, has been extended to other biochemical compounds such as proteins and more recently oligosaccharides. The copolymerization of a pyrrole monomer with a biomolecule bearing a pyrrole group by an electrochemical process allows a very fast coupling of the biomolecule (probe) to a gold layer used as a working electrode. Fluorescence-based detection is the reference method to detect interactions on biochips; however an alternative label free method, could be more convenient for rapid screening of biointeractions. Surface Plasmon Resonance (SPRi) is a typical label-free method for real time detection of the binding of biological molecules onto functionalized surfaces. This surface sensitive optical method is based upon evanescent wave sensing on a thin metal layer. The SPR approach described herein is performed in an imaging geometry that allows simultaneous monitoring of biorecognition reactions occurring on an array of immobilized probes (chip). In a SPR imaging experiment, local changes in the reflectivity are recorded with a CCD camera and are exploited to monitor up to 100 different biological reactions occurring onto the molecules linked to the polypyrrole matrix. This method will be applied to oligosaccharide recognition. PMID- 22057519 TI - Glycosylated self-assembled monolayers for arrays and surface analysis. AB - Over the past few decades, carbohydrates (glycans) have received growing attention for their many roles in biological systems, including pathogenesis, receptor-ligand interactions, and cell signaling. To unravel the biology of this important category of biomolecules, a host of new tools have been developed for glycomics investigation. At the forefront is the carbohydrate microarray, developed to immobilize functional glycans on a solid substrate to rapidly screen a variety of potential binding partners (carbohydrates, proteins, nucleic acids, cells, and viruses). The essential role played by surface modification on glycan microarray performance requires new methods to rigorously characterize glycan surface chemistries. Due to their highly reproducible nature and well-studied properties, self-assembled monolayers (SAMs) on gold are powerful models for presenting glycans on a solid substrate, engineering biomimetic microenvironments and exploring the bioactivity of immobilized carbohydrates via surface plasmon resonance (SPR). However, it can be challenging to prepare high quality glycosylated SAMs (glyco-SAMs) that retain their biological function following surface immobilization. Herein, a selection of versatile methods for the preparation of glyco-SAMs using natural and chemically modified glycans is described. This chapter will highlight the following three immobilization techniques: (1) direct self assembly using thiolated glycosides onto gold, (2) tethering aminated glycosides onto -amine-reactive SAMs, and (3) conjugating natural glycan onto divinyl sulfone-activated SAMs. PMID- 22057520 TI - Carbohydrate microarrays for enzymatic reactions and quantification of binding affinities for glycan-protein interactions. AB - Glycans are involved in a variety of physiological and pathological processes through interactions with proteins. Thus, the molecular basis of glycan-protein interactions provides valuable information on understanding biological phenomena and exploiting more effective carbohydrate-based therapeutic agents and diagnostic tools. Carbohydrate microarray technology has become a powerful tool for evaluating glycan-mediated biological events in a high-throughput manner. This technology is mostly applied for rapid analysis of glycans-protein interactions in the field of functional glycomics. In order to expand application areas of glycan microarrays, we have used carbohydrate microarrays for measurement of binding affinities between glycans and proteins and profiling of glycosyltransferase activities. The glycan microarrays used for these studies are constructed by immobilizing maleimide or hydrazide-conjugated glycans on the thiol or hydrazide-derivatized glass slides, respectively. This protocol describes the fabrication of carbohydrate microarrays and their applications to enzymatic reactions and determination of quantitative binding affinities. PMID- 22057521 TI - Neoglycolipid-based oligosaccharide microarray system: preparation of NGLs and their noncovalent immobilization on nitrocellulose-coated glass slides for microarray analyses. AB - Carbohydrate microarrays, since their advent in 2002, are revolutionizing studies of the molecular basis of protein-carbohydrate interactions both in endogenous recognition systems and pathogen-host interactions. We have developed a unique carbohydrate microarray system based on the neoglycolipid (NGL) technology, a well-validated microscale approach for generating lipid-tagged oligosaccharide probes for use in carbohydrate recognition studies. This chapter provides an overview of the principles and key features of the NGL-based oligosaccharide microarrays, and describes in detail the basic techniques - from the preparation of NGL probes to the generation of microarrays using robotic arraying hardware, as well as a general protocol for probing the microarrays with carbohydrate binding proteins. PMID- 22057522 TI - Preparation of a mannose-6-phosphate glycan microarray through fluorescent derivatization, phosphorylation, and immobilization of natural high-mannose N glycans and application in ligand identification of P-type lectins. AB - Glycan microarrays prepared by immobilization of amino-functionalized glycans on NHS-activated glass slides have been successfully used to study protein-glycan interactions. Fluorescently tagged glycans with an amino functional group can be prepared from natural glycans released from glycoproteins. These tagged glycans can be enzymatically modified with various glycosyltransferases, phosphotransferases, sulfotransferases, etc., to quickly expand the size and diversity of the tagged glycan libraries (TGLs). The TGLs, presented in the format of microarrays, provide a convenient platform for identifying the glycan ligands of glycan-binding proteins (GBPs). The chapter provides the background to prepare a defined glycan microarray and uses as an example glycans generated as phosphodiesters and phosphomonoesters of high-mannose type N-glycans. The method describes the preparation of high-mannose type glycan-AEAB conjugates (GAEABs), the purification of their phosphodiesters, and the subsequent mild acid hydrolysis to obtain corresponding phosphomonoesters. These GAEABs are covalently printed as a phosphorylated glycan microarray and used for analysis of the glycan ligand specificities of P-type lectins, such as the mannose-6-phosphate receptors (Man-6-P receptors or MPRs). PMID- 22057523 TI - Production of fluorous-based microarrays with uncharged carbohydrates. AB - Fluorous-based carbohydrate microarrays provide an alternative to traditional covalent microarray -platforms for probing protein-carbohydrate-binding interactions. The most studied plant lectin, concanavalin A (ConA), is known to bind to terminally alpha-linked mannose. In the studies presented, the binding of ConA with alpha-mannose is analyzed using a microarray formed on a fluorous coated glass slide with the sugar containing a fluorous tag at the anomeric position. PMID- 22057524 TI - General procedure for the synthesis of neoglycoproteins and immobilization on epoxide-modified glass slides. AB - Neoglycoproteins, such as BSA-glycosides, contain carbohydrates covalently attached to a protein carrier via nonnaturally occurring linkages. These conjugates have been used for decades to study carbohydrate-protein interactions and are frequently used as immunogens to raise antibodies to carbohydrate antigens. In fact, neoglycoproteins have been used extensively as vaccine antigens and several have obtained FDA approval. More recently, neoglycoproteins have been used in the construction of glycan arrays to produce "neoglycoprotein microarrays." In this chapter, two methods for preparing neoglycoproteins are described along with methods to immobilize these conjugates on epoxide-coated glass microscope slides to produce arrays. PMID- 22057525 TI - Immobilization of polyacrylamide-based glycoconjugates on solid phase in immunosorbent assays. AB - Our experience in coating of solid surfaces with glycans, mainly for obtaining routine glycoarrays based on immunological plates, is summarized. Three polystyrene coating techniques are described: direct physical adsorption, covalent binding, and immobilization using the biotin tag. Protocols for studies on anticarbohydrate antibodies are considered, with special emphasis on the application niches of different immobilization techniques as related to the specificity of each method of glycan-binding protein assay, as well as the problems of background binding and quantitative estimation of the results. PMID- 22057526 TI - Surface plasmon resonance imaging analysis of protein binding to a sialoside based carbohydrate microarray. AB - Monitoring multiple biological interactions in a multiplexed array format has numerous advantages. However, converting well-developed surface chemistry for spectroscopic measurements to array-based, high-throughput screening is not a trivial process and often proves to be the bottleneck in method development. This chapter reports the fabrication and characterization of a new carbohydrate microarray with synthetic sialosides for surface plasmon resonance imaging analysis of lectin-carbohydrate interactions. Contact printing of functional sialosides on neutravidin-coated surfaces was carried out and the properties of the resulting elements were characterized by fluorescence microscopy. Sambucus nigra agglutinin (SNA) was used for testing on four different carbohydrate functionalized surfaces and differential binding was analyzed. Multiplexed detection of SNA/biotinylated sialoside interactions on arrays up to 400 elements has been performed with good data correlation, demonstrating the effectiveness of the biotin-neutravidin-based biointerface to control probe orientation for reproducible and efficient protein binding to carbohydrates. PMID- 22057527 TI - Glycoarray by DNA-directed immobilization. AB - Glycoarrays have become a powerful platform to investigate the interactions of many biological events involving carbohydrates. The carbohydrates immobilization on the surface of the substrates is a key step of glycoarray fabrication. Plenty of strategies have been applied to the immobilization process. Herein a protocol for the synthesis of oligonucleotide glycomimetic conjugates is proposed. The resulting molecules are immobilized by hybridization on a DNA microarray (DNA directed immobilization; DDI). DDI has been proved to be a very efficient and site-selective. This protocol provides detailed procedures for the preparation of fluorescent oligonucleotide trigalactosylmimetic conjugates and for the preparation of carbohydrate microarrays by DDI on glass slides. PMID- 22057528 TI - Fabrication of carbohydrate surfaces by using non-derivatised oligosaccharides. AB - Surface-based tools, such as microarrays and optical biosensors, are being increasingly applied to the analysis of carbohydrate-protein interactions. A key to these developments is the presentation of the carbohydrate to the protein target. Dual polarisation interferometry (DPI) is a surface-based technique that permits the real-time measurement of the changes in thickness, refractive index, and mass of adsorbates 100-nm thick or less on the surface of a functionalised waveguide. DPI has been used to design and characterise a surface on which the orientation and density of the immobilised carbohydrates are suitable for studying their interactions with proteins and where non-specific binding is reduced to less than 5% of total binding. A thiol-functionalised surface was derivatised with a heterobifunctional cross-linker to yield a hydrazide surface. This was treated with oligosaccharides, derived from keratan sulphate, chondroitin sulphate, and heparin that possess a reducing end. To block the unreacted hydrazide groups, the surface was treated with an aldehyde functionalised PEG, and the surfaces were then challenged with a variety of proteins. PMID- 22057529 TI - Polysaccharide microarrays: application to the identification of heparan sulphate mimetics. AB - The interaction of polysaccharides with proteins modulates or triggers many biological effects. In particular, heparan sulphate proteoglycans (HSPGs) have multiple regulatory interactions with growth factors, enzymes, enzyme inhibitors, and some components of the extracellular matrix. The important role played by HSPGs has motivated the synthesis and selection of HSPG mimetics for modulating the biological activity of HS-binding proteins. We present hereinafter an efficient polysaccharide microarray method that allows the screening of HS mimetic libraries towards HS-binding growth factors, a major class of polypeptides whose inhibition or potentiation is of high medical interest. PMID- 22057530 TI - Carbohydrate antigen microarrays. AB - This chapter describes one of my laboratory's working protocols for carbohydrate based microarrays. Using a standard microarray spotter, we print carbohydrate antigens directly on the nitrocellulose-coated bioarray substrates. Because these substrates support noncovalent immobilization of many spotted antigens, in general no chemical modification of the antigen is needed for microarray production. Thus, this bioarray platform is technically simple and applicable for high-throughput construction of carbohydrate antigen microarrays. A number of nitrocellulose-coated glass slides with different technical characteristics are commercially available. Given the structural diversity of carbohydrate antigens, examining each antigen preparation to determine the efficacy of its immobilization in a given type of substrate and the surface display of the desired glycoepitopes in a microarray assay is essential. PMID- 22057531 TI - Probing virus-glycan interactions using glycan microarrays. AB - Glycan microarrays are surfaces that contain immobilized oligosaccharides or glycoconjugates and have proven useful in probing the interactions between glycan binding proteins (GBPs) and individual glycans. Such glycan microarrays have been especially important in studying virus-glycan interactions, as most viruses express one or more GBPs important for pathogenesis. For studying interactions of influenza viruses with glycans, we describe protocols for fluorescent labeling of virus, addition of virus to a glycan microarray, analysis of a glycan microarray slide experiment, and interpretation of data. PMID- 22057532 TI - MALDI-ToF MS analysis of glycosyltransferase activities on gold surface arrays. AB - Glycan-processing enzymes such as glycosyltransferases and glycosidases are responsible for the makeup of the glycome. The definition of their substrate specificities is, therefore, a central task in glycomics. In addition, these enzymes are themselves useful synthetic tools for the generation of complex carbohydrate structures as an alternative to tedious chemical synthesis. There has been great interest in using microarrays for studying these glycoenzymes because it allows the specificity of the enzyme to be probed against a panel of immobilized potential substrates, and also expands the repertoire of sugar arrays available for further carbohydrate-protein interaction studies. In particular, self-assembled monolayers (SAMs) of alkanethiols on gold surfaces have proven to be a valuable platform for such studies due to their robustness and their biocompatible, well-defined structure. Furthermore, a direct observation of the change in mass of immobilized substrates due to enzymatic processing is possible through label-free MALDI-ToF MS (matrix-assisted laser desorption/ionization time of-flight mass spectrometry) technique. In this chapter, we describe the preparation of SAMs-coated gold surface arrays presenting carbohydrate or (glyco)peptide substrates, either pre-formed or directly synthesized on-chip, and MALDI-ToF MS analysis of glycosyltransferase activities on these immobilized substrates. PMID- 22057533 TI - Microarray technology using glycans extracted from natural sources for serum antibody fluorescent detection. AB - Glycan microarray technology enables the screening of large numbers of glycan samples for glycan-protein interactions, based on the presentation of immobilized glycans in a discrete pattern on a solid support. Here we describe a glycan microarray approach employing glycans enzymatically released from proteins and lipids of in vitro cultured cells and of human and animal tissues, followed by the detection of serum antibody binding. This approach may be used to detect autoantibodies in cancer as well as in autoimmune diseases. PMID- 22057534 TI - Studying modification of aminoglycoside antibiotics by resistance-causing enzymes via microarray. AB - Widespread bacterial resistance to antibiotics is a significant public health concern. To remain a step ahead of evolving bacteria, new methods to study resistance to antibacterials and to uncover novel antibiotics that evade resistance are urgently needed. Herein, microarray-based methods that have been developed to study aminoglycoside modification by resistance-causing enzymes are reviewed. These arrays can also be used to study the binding of aminoglycoside antibiotics to a mimic of their therapeutic target, the rRNA aminoacyl site (A site), and how modification by resistance-causing enzymes affects their abilities to bind RNA. PMID- 22057535 TI - Microarray method for the rapid detection of glycosaminoglycan-protein interactions. AB - Glycosaminoglycans (GAGs) perform numerous vital functions within the body. As major components of the extracellular matrix, these polysaccharides participate in a diverse array of cell-signaling events. We have developed a simple microarray assay for the evaluation of protein binding to various GAG subclasses. In a single experiment, the binding to all members of the GAG family can be rapidly determined, giving insight into the relative specificity of the interactions and the importance of specific sulfation motifs. The arrays are facile to prepare from commercially available materials. PMID- 22057536 TI - Neoglycolipid-based "designer" oligosaccharide microarrays to define beta-glucan ligands for Dectin-1. AB - In this chapter, we describe the key steps of the "designer" oligosaccharide microarray approach we followed to prove the carbohydrate binding activity and define the oligosaccharide ligands for Dectin-1, an atypical C-type lectin-like signaling receptor of the mammalian innate immune system with a key role in anti fungal immunity. The term "designer" microarray, which we introduced in the course of the Dectin-1 study refers to a microarray of oligosaccharide probes generated from ligand-bearing glycoconjugates to reveal the oligosaccharide ligands they harbor, so that these can be isolated and characterized. Oligosaccharide probes were generated from two polysaccharides, one that was bound by Dectin-1 and known to be rich in beta1,3-glucose sequence and another that was not bound and was rich in beta1,6-glucose sequence and served as a negative control. The approach involved: classic ELISA-type binding assays to select the polysaccharides; partial depolymerization of the polysaccharides by chemical hydrolysis; fractionation by size of the glucan oligosaccharides obtained and determination of their chain lengths by mass spectrometry; detection of Dectin-1 ligand-positive and ligand-negative oligosaccharides using the neoglycolipid (NGL) technology; methylation analysis of oligosaccharides to derive glucose linkage information, and incorporation of the newly generated glucan oligosaccharide probes into microarrays encompassing diverse mammalian type and exogenous sequences for microarray analysis of Dectin-1. PMID- 22057537 TI - Measurement of antibodies to pneumococcal polysaccharides with Luminex xMAP microsphere-based liquid arrays. AB - The 23 valent pneumococcal polysaccharide vaccine (PPV) is often used to assess an individual's ability to produce antibodies to polysaccharides. The Luminex xMAP microsphere-based liquid array system, when applied to the determination of antibodies to pneumococcal polysaccharides (PnPs), allows for the antibody response to the 23 serotypes to be determined simultaneously. Multiplexing saves considerable time and expense over the traditional method of testing each PnPs serotype individually by the enzyme-linked immunosorbent assay (ELISA). This chapter describes methods for (a) conjugation of poly-L: -lysine (PLL) to PnPs, (b) coupling of PnPs-PLL conjugates to Luminex microspheres, and (c) a multiplex Luminex assay for the measurement of serotype-specific IgG concentrations to pneumococcal serotypes. PMID- 22057538 TI - Carbohydrate microarrays in 96-well polystyrene microtiter plates. AB - A method for the preparation of carbohydrate microarrays inside 96-well polystyrene microtiter plates is described. The key step in this strategy represents the synthesis of carbohydrate-dextran conjugates by copper (I) catalyzed [3 + 2] cycloaddition between alkyne carbohydrate derivative and a specially designed azido dextran polymer. The conjugates adsorb efficiently on polystyrene surface and can be printed inside 96-well plates using a non-contact piezoelectric microarrayer. Model interactions with a selection of lectins (concanavalin A, wheat germ agglutinin, Erythrina Cristagalli) display the efficiency of the immobilization method, its reproducibility and the specificity of biomolecular interactions occurring at the polystyrene-water interface. PMID- 22057539 TI - Photoimmobilization of saccharides. AB - Interest in understanding the biological information content of carbohydrates has led to the development of a variety of methodologies for preparing carbohydrate microarrays. A key challenge is to find a general method to make carbohydrate molecules adhere to a solid chip in a stable manner while preserving the biorecognition properties present when in their native biological environment. The complexity of carbohydrates makes chemical modification prior to surface deposition rigorous when large libraries of surface-immobilized sugars are desired. In this report, we review a versatile photochemical method to carbohydrate immobilization that does not require premodification of the carbohydrate. The method utilizes surfaces modified with photoactive carbonyls that can insert into C-H bonds upon photoexcitation. PMID- 22057540 TI - Microwave-assisted method for fabrication of carbohydrate cluster microarrays on 3-dimensional hydrazide-dendrimer substrate. AB - We present here a method for construction of carbohydrate cluster microarrays. This technology utilizes a 3-dimensional poly(amidoamine) starburst dendrimer monolayer assembled on glass surface, which is functionalized with terminal hydrazide groups for site-specific coupling of carbohydrates without prior chemical derivatization. Microwave radiation energy is applied to accelerate carbohydrate coupling on chips. Since this bioarray platform is designed to present sugar chains in defined orientation and cluster configurations, it is particularly suitable for exploration of the structural and conformational diversities of glycoepitopes and their functional properties. PMID- 22057541 TI - Combinatorial glycoarray. AB - Glycolipid-protein interactions are increasingly recognised as critical to numerous and diverse biological processes, including immune recognition, cell cell signalling, pathogen adherence, and virulence factor binding. Previously, such carbohydrate-lectin interactions have been assessed in vitro largely by assaying protein binding against purified preparations of single glycolipids. Recent observations show that certain disease-associated autoantibodies and other lectins bind only to complexes formed by two different gangliosides. However, investigating such 1:1 glycolipid complexes can prove technically arduous. To address this problem, we have developed a semi-automated system for assaying lectin binding to large numbers of glycolipid complexes simultaneously. This employs an automated thin-layer chromatography sampler. Single glycolipids and their heterodimeric complexes are prepared in microvials. The autosampler is then used to print reproducible arrays of glycolipid complexes onto polyvinylidene difluoride membranes affixed to glass slides. A printing density of 300 antigen spots per slide is achievable. Following overnight drying, these arrays can then be probed with the lectin(s) of interest. Detection of binding is by way of a horseradish peroxidase-linked secondary antibody driving a chemiluminescent reaction rendered on radiographic film. Image analysis software can then be used to measure signal intensity for quantification. PMID- 22057542 TI - Evaluation of acute cervical spine imaging based on ACR Appropriateness Criteria(r). AB - The objectives of this study were to determine the rate of acute blunt cervical spine injury at an academic urban level 1 trauma center and to evaluate the utilization of cervical spine imaging based on the established American College of Radiology (ACR) Appropriateness Criteria(r). We retrospectively reviewed all radiography and CT imaging of the cervical spine performed over a year period in adult patients presenting with acute blunt cervical spine trauma. Exclusion criteria were children <=17 years, non-acute trauma of >=72 h, and penetrating trauma. Any fracture, dislocation, or ligamentous instability demonstrated by diagnostic imaging and requiring stabilization or specialized follow-up was defined as clinically significant cervical spine injury. A total of 1,325 cervical spine studies were reviewed in 1,245 patients; 32.7% (433/1,325) were cervical spine radiographs and 67.3% (892/1,325) were CT examinations. Approximately 1.5% (19/1,245) of the patients demonstrated clinically significant acute cervical spine injury. There were 6.4% (80/1,245) patients who received both cervical spine radiographs and CT as imaging evaluation. Based on the ACR Appropriateness Criteria(r), all of the cervical spine radiographs performed (433) were determined to be "inappropriate" imaging in the setting of acute cervical spine injury. PMID- 22057543 TI - Protein secretion in Pichia pastoris and advances in protein production. AB - Yeast expression systems have been successfully used for over 20 years for the production of recombinant proteins. With the growing interest in recombinant protein expression for various uses, yeast expression systems, such as the popular Pichia pastoris, are becoming increasingly important. Although P. pastoris has been successfully used in the production of many secreted and intracellular recombinant proteins, there is still room for improvement of this expression system. In particular, secretion of recombinant proteins is still one of the main reasons for using P. pastoris. Therefore, endoplasmic reticulum protein folding, correct glycosylation, vesicular transport to the plasma membrane, gene dosage, secretion signal sequences, and secretome studies are important considerations for improved recombinant protein production. PMID- 22057544 TI - Direct and cell signaling-based, geometry-induced neuronal differentiation of neural stem cells. AB - Neural Stem Cells (NSCs) are multipotent precursors inhabiting the subventricular and hippocampal subgranular regions of the adult mammalian brain, able to self renew and differentiate into neurons, astrocytes, and oligodendrocytes, the three primary neural cell types of the adult brain. NSC fate is influenced by the physical and chemical microenvironment experienced by the cell, both in vitro and in vivo. Towards characterizing the influence of topographical, geometric cues on NSC fate, we fabricated highly aligned, single- and double-layer polystyrene nanofiber meshes. Seeding of NSCs on laminin-coated fibers induces polarized NSC morphology and cellular elongation in the directions of fiber alignment, with cells extending membranous processes over hundreds of microns along the fiber surfaces. Additionally, these aligned fiber substrates promote neuronal lineage specification of NSCs with an efficiency of 82.3 +/- 11.1% within days of seeding. Moreover, not only do cells on fibers yield neurons, but also neighboring cells in close proximity to those differentiating on aligned fibers, with an efficiency of 72.8 +/- 9.7%. This neighboring, cell-induced differentiation occurs without cell-cell contact over millimetres away from the fibers, suggesting a paracrine signaling effect not previously reported for NSCs undergoing neurogenesis. In contrast, NSCs farther away from these fiber substrates nearly uniformly yield glia. PMID- 22057545 TI - High efficient expression of bioactive human BMP-14 in E. coli using SUMO fusion partner. AB - Bone morphogenetic proteins (BMPs) are cytokines from the TGF-beta superfamily, with important roles during embryonic development and in the induction of bone and cartilage tissue differentiation in the adult body. In this contribution, We report here the application of small ubiquitin-related modifier (SUMO) fusion technology to the expression and purification of human BMP-14. The fusion protein expressed in a soluble form was purified to a purity of 90% by Ni-IDA chromatography. After the SUMO-BMP14 fusion protein was cleaved by the SUMO protease at 30 degrees C for 1 h, the cleaved sample was re-applied to a Ni-IDA. Finally, about 45 mg recombinant hBMP-14 was obtained from 1 litre bacterial culture with no less than 95% purity. The purified hBMP-14 dimer was over 90% purity and could induce the expression of alkaline phosphatase activity in C2C12 cells in a dose-dependent manner. Thus the SUMO-mediated peptide expression and purification system potentially could be employed for the production of other homodimeric proteins. PMID- 22057546 TI - Electrochemical control of growth factor presentation to steer neural stem cell differentiation. AB - Let it grow: The conjugated polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was synthesized with heparin as the counterion to form a cell culture substrate. The surface of PEDOT:heparin in the neutral state associated biologically active growth factors. Electrochemical in situ oxidation of PEDOT during live cell culture decreased the bioavailability of the growth factor and created an exact onset of neural stem cell differentiation. PMID- 22057547 TI - Molecular cloning, characterization expression of P450c17-I and P450c17-II and their functions analysis during the reproductive cycle in males of barfin flounder (Verasper moseri). AB - P450c17, a key steroidogenic enzyme, plays important roles in the production of sex steroid and cortisol. In teleost, there are two types of P450c17, P450c17-I possessing 17alpha-hydroxylase and 17, 20-lyase activities, and P450c17-II only possessing 17alpha-hydroxylase activity. This work describes the molecular cloning of the cDNA encoding the barfin flounder (Verasper moseri) P450c17-I and P450c17-II by means of RT-PCR and 5' and 3' rapid amplification of cDNA ends (RACE) analyses and mRNA expression profiles analyzing by semiquantitative RT PCR. Respectively, P450c17-I and P450c17-II mRNA levels in the testes correlated with serum testosterone (T) level, as well as gonadosomatic index (GSI) of males during specific stages of spermatogenesis. P450c17-I and P450c17-II mRNA were expressed in the testis and ovary, suggesting that both of them participate in the production of sex steroid in barfin flounder gonads. P450c17-I mRNA was undetectable; in contrast, P450c17-II mRNA was detected at the highest level in the head kidney, meaning that only P450c17-II is involved in the production of cortisol in barfin flounder. The results demonstrated that both of P450c17-I and P450c17-II participate in the production of sex steroid in male barfin flounder gonads. PMID- 22057548 TI - A significant association exists between receptor tyrosine kinase-like orphan receptor 2 gene variants and the OPG/RANKL ratio in human plasma. AB - SUMMARY: There is a paucity of studies investigating association between ROR2 gene variants and osteoporosis and osteoarthritis-related phenotypes. The published literature suggests that osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) are essential for bone metabolism and correlate with osteoarthritis manifestation and progression. The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma. The present results also suggest significant association between ROR2 polymorphisms and severity of radiographic hand osteoarthritis. INTRODUCTION: Despite the importance of the ROR-2 in skeletal physiology, there is a paucity of studies investigating the potential association of ROR2 gene variants with phenotypes relevant to osteoporosis and osteoarthritis. On the other hand, there is a considerable body of literature suggesting that OPG and RANKL and their ratio (OPG/RANKL) are essential for regulating bone resorption. This is also correlated with osteoarthritis manifestation and progression. The present study therefore examines whether ROR2 polymorphisms may be associated with the OPG/RANKL ratio and hand osteoarthritis (HOA). METHODS: The study was conducted in a family-based sample of 1,515 Caucasian individuals, assessed for radiographic hand osteoarthritis, using the Kellgren/Lawrence score. Of these, 865 individuals were genotyped for 19 SNPs, relatively equally covering the ROR2 locus, and their plasma levels of OPG and RANKL were assayed. The association between the selected SNPs and OPG, along with the OPG/RANKL ratio and HOA, was explored using the pedigree disequilibrium test. RESULTS: Of the total of 57 tests, 16 nominally significant results (p < 0.05) were obtained, which is considerably more than the three normally expected for type I error. The significant association signals for all three phenotypes were mapped to the intron 1 region. The most significant results were detected between OPG/RANKL and rs7048756 (p < 0.0005) and between adjacent rs4744107 and Kellgren/Lawrence score (p = 0.006). CONCLUSIONS: The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma and also suggests ROR2 association with HOA. PMID- 22057549 TI - Risk factors for osteoporosis in long-term survivors of intracranial germ cell tumors. AB - SUMMARY: We measured bone mineral densities in 28 intracranial germ cell tumor long-term survivors. There was the high prevalence of osteoporosis and osteopenia, 25.0% and 42.9%, respectively, and three additional risk factors, male sex, a low lean mass, and adult growth hormone replacement, were identified. INTRODUCTION: Intracranial germ cell tumor long-term survivors (iGCTLS) have many risk factors for osteoporosis, including irradiation from cancer therapy and multiple hormone deficiencies. However, no study of bone mineral density (BMD) has been conducted in iGCTLS because these tumors are rare. The aims of this study were to evaluate the prevalence of osteoporosis and to identify risk factors associated with reduced bone mass in iGCTLS. METHODS: We evaluated BMD and body composition of 28 iGCTLS (10.9 +/- 5.2 years after cancer treatment; 13 males) using dual-energy X-ray absorptiometry. To determine risk factors, we analyzed the medical history, including the nature of the tumor, treatment modality, endocrine status, hormone replacement therapy, lifestyle, and biochemical parameters. RESULTS: Twenty-five percent of iGCTLS were diagnosed with osteoporosis and 42.9% with osteopenia. Most males (92.3%) had low BMD. Lean mass (LM) was positively correlated with BMD in all regions of interest, and the starting age of adult growth hormone (GH) replacement was negatively correlated with the BMD Z-score at the femur neck. In logistic regression analysis, male sex and low LM were related to low BMD. CONCLUSIONS: The iGCTLS had a high prevalence of low BMD. We found that male sex, low LM, and delayed start of adult GH replacement were risk factors for osteoporosis. Therefore, the BMD of all iGCTLS should be evaluated, and if it is low, proper management should be started early. PMID- 22057550 TI - Relationship of femoral neck areal bone mineral density to volumetric bone mineral density, bone size, and femoral strength in men and women. AB - Using combined dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography, we demonstrate that men matched with women for femoral neck (FN) areal bone mineral density (aBMD) have lower volumetric BMD (vBMD), higher bone cross-sectional area, and relatively similar values for finite element (FE) derived bone strength. INTRODUCTION: aBMD by DXA is widely used to identify patients at risk for osteoporotic fractures. aBMD is influenced by bone size (i.e., matched for vBMD, larger bones have higher aBMD), and increasing evidence indicates that absolute aBMD predicts a similar risk of fracture in men and women. Thus, we sought to define the relationships between FN aBMD (assessed by DXA) and vBMD, bone size, and FE-derived femoral strength obtained from quantitative computed tomography scans in men versus women. METHODS: We studied men and women aged 40 to 90 years and not on osteoporosis medications. RESULTS: In 114 men and 114 women matched for FN aBMD, FN total cross-sectional area was 38% higher (P < 0.0001) and vBMD was 16% lower (P < 0.0001) in the men. FE models constructed in a subset of 28 women and 28 men matched for FN aBMD showed relatively similar values for bone strength and the load-to-strength ratio in the two groups. CONCLUSIONS: In this cohort of young and old men and women from Rochester, MN, USA who are matched by FN aBMD, because of the offsetting effects of bone size and vBMD, femoral strength and the load-to-strength ratio tended to be relatively similar across the sexes. PMID- 22057552 TI - High prevalence of Eimeria infection in dairy goats in Shaanxi province, northwestern China. AB - A survey of dairy goats for infection with Eimeria species of coccidia was conducted in the Shaanxi province, northwestern China between December and November 2010, including Saanen and Guanzhong breeds. A total of 584 fecal samples (250 and 334 from Saanen and Guanzhong dairy goats, respectively) in six farms were collected. Eimeria oocysts were seen in 568 (97.3%) fecal samples, with six species, namely Eimeria jolchijevi, Eimeria arloingi, Eimeria alijevi, Eimeria caprina, Eimeria hirci, and Eimeria christenseni. The most prevalent were E. arloingi in Saanen and Guanzhong dairy goats, with an overall prevalence of 83.3% and 84.4%, and the lowest prevalence were E. christenseni (26.9%) and E. hirci (20.7%) for Saanen and Guanzhong Dairy goats, respectively. Two or more Eimeria species were commonly presented in all the age groups; 80.0% and 81.4% of positive Saanen and Guanzhong dairy goats carried more than two species, and 1.6% and 6.5% of two breeds had six species. The results of the present survey suggested that Eimeria infection is wide and severe in the Saanen and Guanzhong dairy goats, which suggested that integrated strategies should be implemented to prevent and control coccidial infection in dairy goats in this province. PMID- 22057551 TI - The evolution of menstruation: a new model for genetic assimilation: explaining molecular origins of maternal responses to fetal invasiveness. AB - Why do humans menstruate while most mammals do not? Here, we present our answer to this long-debated question, arguing that (i) menstruation occurs as a mechanistic consequence of hormone-induced differentiation of the endometrium (referred to as spontaneous decidualization, or SD); (ii) SD evolved because of maternal-fetal conflict; and (iii) SD evolved by genetic assimilation of the decidualization reaction, which is induced by the fetus in non-menstruating species. The idea that menstruation occurs as a consequence of SD has been proposed in the past, but here we present a novel hypothesis on how SD evolved. We argue that decidualization became genetically stabilized in menstruating lineages, allowing females to prepare for pregnancy without any signal from the fetus. We present three models for the evolution of SD by genetic assimilation, based on recent advances in our understanding of the mechanisms of endometrial differentiation and implantation. Testing these models will ultimately shed light on the evolutionary significance of menstruation, as well as on the etiology of human reproductive disorders like endometriosis and recurrent pregnancy loss. PMID- 22057553 TI - Titanium dioxide-assisted photocatalytic induction of prophages to lytic cycle. AB - The investigations on the kinetics of photocatalytic inactivation of bacteriophages, lactic bacteria and lysogenic lactic bacteria have shown that the rate of bacterial inactivation is ca. 10 times less than the inactivation of bacteriophages. Titania-assisted photorelease of bacteriophages from lysogenic bacteria proves that photogenerated reactive oxygen species affect the deoxyribonucleic acid (DNA) of bacteria before their deactivation. On this basis a novel photocatalytic method of a prophage induction to the lytic cycle and detection of lysogenic bacteria is proposed. PMID- 22057554 TI - Reference curves for the Brazilian Alberta Infant Motor Scale: percentiles for clinical description and follow-up over time. AB - OBJECTIVES: To compare Alberta Infant Motor Scale scores for Brazilian infants with the Canadian norm and to construct sex-specific reference curves and percentiles for motor development for a Brazilian population. METHODS: This study recruited 795 children aged 0 to 18 months from a number of different towns in Brazil. Infants were assessed by an experienced researcher in a silent room using the Alberta Infant Motor Scale. Sex-specific percentiles (P5, P10, P25, P50, P75 and P90) were calculated and analyzed for each age in months from 0 to 18 months. RESULTS: No significant differences (p > 0.05) between boys and girls were observed for the majority of ages. The exception was 14 months, where the girls scored higher for overall motor performance (p = 0.015) and had a higher development percentile (0.021). It was observed that the development curves demonstrated a tendency to nonlinear development in both sexes and for both typical and atypical children. Variation in motor acquisition was minimal at the extremes of the age range: during the first two months of life and from 15 months onwards. CONCLUSIONS: Although the Alberta Infant Motor Scale is widely used in both research and clinical practice, it has certain limitations in terms of behavioral differentiation before 2 months and after 15 months. This reduced sensitivity at the extremes of the age range may be related to the number of motor items assessed at these ages and their difficulty. It is suggested that other screening instruments be employed for children over the age of 15 months. PMID- 22057555 TI - Thermally stable, dye-bridged nanohybrid-based white light-emitting diodes. AB - Thermally stable red and green light-emitting nanohybrids are introduced as an organic luminescent converter with broad color tunability and a high color rendering index for white light-emitting diodes (LEDs). Nanohybrid-based white LEDs are thermally stable and the color coordination is not changed by heat exposure. PMID- 22057556 TI - Thymic stromal lymphopoietin (TSLP) acts as a potent mucosal adjuvant for HIV-1 gp140 vaccination in mice. AB - The development of a successful vaccine against HIV is likely to require the induction of strong and long-lasting humoral immune responses at the mucosal portal of virus entry. Hence, the design of a vaccine strategy able to induce mucosal antibodies and in particular specific IgA, may be crucial to providing immune protection. Nasal immunisation is known to induce specific IgG and IgA responses in the cervicovaginal mucosa; however, there is an urgent need for the development of safe, effective and accessible mucosal adjuvants for nasal application in humans. To reduce the potential for adverse events associated with some nasal adjuvants, we have assessed whether the B-cell-activating cytokines APRIL, BAFF and TSLP enhance humoral immune responses to HIV-1 gp140. Following intranasal immunisation, TSLP but not APRIL or BAFF induced strong humoral responses both in serum and mucosa. The adjuvant effect of TSLP on humoral responses was similar to that of cholera toxin (CT). The use of TSLP as an adjuvant skewed both the cellular and humoral immune responses towards Th2 cells. This is the first time that TSLP has been demonstrated to have a positive effect as a mucosal adjuvant, and specifically to promote mucosal and systemic responses to HIV gp140. PMID- 22057557 TI - Overview of mitochondrial bioenergetics. AB - Bioenergetic Science started in seventh century with the pioneer works by Joseph Priestley and Antoine Lavoisier on photosynthesis and respiration, respectively. New developments were implemented by Pasteur in 1860s with the description of fermentations associated to microorganisms, further documented by Buchner brothers who discovered that fermentations also occurred in cell extracts in the absence of living cells. In the beginning of twentieth century, Harden and Young demonstrated that orthophosphate and other heat-resistant compounds (cozymase), later identified as NAD, ADP, and metal ions, were mandatory in the fermentation of glucose. The full glycolysis pathway has been detailed in 1940s with the contributions of Embden, Meyeroff, Parnas, Warburg, among others. Studies on the citric acid cycle started in 1910 (Thunberg) and were elucidated by Krebs et al. in the 1940s. Mitochondrial bioenergetics gained emphasis in the late 1940s and 1950s with the works of Lenhinger, Racker, Chance, Boyer, Ernster, and Slater, among others. The prevalent "chemical coupling hypothesis" of energy conservation in oxidative phosphorylation was challenged and replaced by the "chemiosmotic hypothesis" originally formulated in 1960s by Mitchell and later substantiated and extended to energy conservation in bacteria and chloroplasts, besides mitochondria, with clear-cut identification of molecular proton pumps. After identification of most reactive mechanisms, emphasis has been directed to structure resolution of molecular complex clusters, e.g., cytochrome c oxidase, complex III, complex II, ATP synthase, photosystem I, photosynthetic water splitting center, and energy collecting antennae of several photosynthetic systems. Modern trends concern to the reactivity of radical and other active species in association with bioenergetic activities. A promising trend concentrates on the cell redox status quantified in terms of redox potentials. In spite of significant development and advances of bioenergetic knowledge, major issues remain mainly related with poor experimental designs not representative of the real native cell conditions. Therefore, a major effort has to be implemented regarding direct observations in situ. PMID- 22057558 TI - Evaluation of respiration with clark type electrode in isolated mitochondria and permeabilized animal cells. AB - In many studies, the evaluation of mitochondrial function is critical to understand how disease conditions or xenobiotics alter mitochondrial function. One of the classic end-points that can be assessed is oxygen consumption, which can be performed under controlled, yet artificial conditions. Oxygen is the terminal acceptor in the mitochondrial respiratory chain, namely at an enzyme called cytochrome oxidase, which produces water in the process and pumps protons from the matrix to the intermembrane space. Several techniques are available to measure oxygen consumption, including polarography with oxygen electrodes or fluorescent/luminescent probes. The present chapter will deal with the determination of mitochondrial oxygen consumption by means of the Clark-type electrode, which has been widely used in the literature and that still remains to be the most reliable technique. We focus our technical description in the measurement of oxygen consumption by isolated mitochondrial fractions and by permeabilized cells. PMID- 22057559 TI - High-resolution respirometry: OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle. AB - Protocols for high-resolution respirometry (HRR) of intact cells, permeabilized cells, and permeabilized muscle fibers offer sensitive diagnostic tests of integrated mitochondrial function using standard cell culture techniques and small needle biopsies of muscle. Multiple substrate-uncoupler-inhibitor titration (SUIT) protocols for analysis of oxidative phosphorylation improve our understanding of mitochondrial respiratory control and the pathophysiology of mitochondrial diseases. Respiratory states are defined in functional terms to account for the network of metabolic interactions in complex SUIT protocols with stepwise modulation of coupling and substrate control. A regulated degree of intrinsic uncoupling is a hallmark of oxidative phosphorylation, whereas pathological and toxicological dyscoupling is evaluated as a mitochondrial defect. The noncoupled state of maximum respiration is experimentally induced by titration of established uncouplers (FCCP, DNP) to collapse the proton gradient across the mitochondrial inner membrane and measure the capacity of the electron transfer system (ETS, open-circuit operation of respiration). Intrinsic uncoupling and dyscoupling are evaluated as the flux control ratio between nonphosphorylating LEAK respiration (electron flow coupled to proton pumping to compensate for proton leaks) and ETS capacity. If OXPHOS capacity (maximally ADP stimulated oxygen flux) is less than ETS capacity, the phosphorylation system contributes to flux control. Physiological Complex I + II substrate combinations are required to reconstitute TCA cycle function. This supports maximum ETS and OXPHOS capacities, due to the additive effect of multiple electron supply pathways converging at the Q-junction. Substrate control with electron entry separately through Complex I (pyruvate + malate or glutamate + malate) or Complex II (succinate + rotenone) restricts ETS capacity and artificially enhances flux control upstream of the Q-cycle, providing diagnostic information on specific branches of the ETS. Oxygen levels are maintained above air saturation in protocols with permeabilized muscle fibers to avoid experimental oxygen limitation of respiration. Standardized two-point calibration of the polarographic oxygen sensor (static sensor calibration), calibration of the sensor response time (dynamic sensor calibration), and evaluation of instrumental background oxygen flux (systemic flux compensation) provide the unique experimental basis for high accuracy of quantitative results and quality control in HRR. PMID- 22057560 TI - High-throughput analysis of mitochondrial oxygen consumption. AB - Interest in the investigation of mitochondrial dysfunction has seen a resurgence over recent years due to the implication of such dysfunction in both drug-induced toxicity and a variety of disease states. Here, we describe a methodology to assist in such investigations whereby the oxygen consumption of isolated mitochondria is assessed in a high-throughput fashion using a phosphorescent oxygen-sensitive probe, standard microtitre plates, and plate reader detection. The protocols provided describe the required isolation procedures, initial assay optimization, and subsequent compound screening. Typical data is also provided illustrating the expected activity levels as well as recommended plate maps and data analysis approaches. PMID- 22057561 TI - Modulation of cellular respiration by endogenously produced nitric oxide in rat hippocampal slices. AB - Nitric oxide (*NO) is a ubiquitous signaling molecule that participates in neuromolecular phenomena associated with memory formation as well as in excitotoxicity. In the hippocampus, neuronal *NO production is coupled to the activation of the NMDA-type of glutamate receptor. More recently, Cytochrome c oxidase has emerged as a novel target for *NO, which competes with O 2 for binding to this mitochondrial complex. This reaction establishes *NO not only as a regulator of cellular metabolism but possibly also as a regulator of mitochondrial production of reactive oxygen species which participate in cellular signaling. A major gap in the understanding of *NO bioactivity, namely, in the hippocampus, has been the lack of knowledge of its concentration dynamics. Here, we present a detailed description of the simultaneous recording of *NO and O2 concentration dynamics in rat hippocampal slices. Carbon fi ber microelectrodes are fabricated and applied for real-time measurements of both gases in a system close to in vivo models. This approach allows for a better understanding of the current paradigm by which an intricate interplay between *NO and O 2 regulates cellular respiration. PMID- 22057562 TI - Mitochondrial membrane potential (DeltaPsi) fluctuations associated with the metabolic states of mitochondria. AB - The study of the mitochondrial membrane potential (DeltaPsi) is essential for an integrated appraisal of mitochondrial function, since it reflects differences in electrical potential and represents the main component of the proton electrochemical gradient accounting for more than 90% of the total available respiratory energy. Numerous methods have been used to estimate mitochondrial membrane potential (DeltaPsi), including fluorescent methods and electrochemical probes. In this chapter, we describe several practical approaches that allow mitochondrial membrane potential (DeltaPsi) evaluation, by using a tetraphenylphosphonium (TPP(+))-selective electrode. The main focus is given to the evaluation of DeltaPsi in isolated mitochondria. PMID- 22057563 TI - Safranine as a fluorescent probe for the evaluation of mitochondrial membrane potential in isolated organelles and permeabilized cells. AB - The mitochondrial electrical membrane potential (Deltapsi) is the main component of the proton motive force (Deltap) generated across the inner mitochondrial membrane during electron flow through the respiratory chain. Among the techniques available to assess Deltapsi, methods that rely on the spectrophotofluorometric responses of dyes are widely employed for whole suspensions of isolated mitochondria or permeabilized cells. Safranine is one of the dyes currently used most often for this purpose. Safranine is a lipophilic cationic dye that undergoes optical shifts upon its potential-dependent distribution between the external medium and the intramitochondrial compartment and on its stacking to inner mitochondrial membrane anionic sites. The association between the optical changes of safranine and the membrane potential allows unknown Deltapsi values to be estimated from an equation describing their relationship. Here, we describe the use of safranine as a fluorescent indicator of Deltapsi in isolated mitochondria and digitonin-permeabilized cells. We present suitable conditions to employ safranine as a Deltapsi indicator. PMID- 22057564 TI - Fluorescence measurement of mitochondrial membrane potential changes in cultured cells. AB - The mitochondrial membrane potential is the dominant component of the proton motive force that is the potential term in the proton circuit linking electron transport to ATP synthesis and other energy-dependent mitochondrial processes. Cationic fluorescent probes have been used for many years to detect gross qualitative changes in mitochondrial membrane potentials in intact cell culture. In this chapter, I describe how these fluorescence signals may be used to obtain a semiquantitative measure of changes in mitochondrial membrane potential. PMID- 22057565 TI - Phenomenological kinetic and control analysis of oxidative phosphorylation in isolated mitochondria. AB - Metabolic control analysis provides a quantitative framework for analyzing regulatory properties of enzymes in various metabolic pathways. It has been used for estimation of control parameters of the enzymatic pathways at isolated enzyme, cellular, or whole organism levels. This chapter describes how control and elasticities analysis can be experimentally applied to measure control properties of the components of the oxidative phosphorylation system and how a variant of such analysis - phenomenological kinetic analysis - can be used to investigate the effects of various factors (physiological or pathological) on the system of oxidative phosphorylation in isolated mitochondria. PMID- 22057566 TI - Expression of uncoupling proteins in a mammalian cell culture system (HEK293) and assessment of their protein function. AB - Immortalised cultured cells are powerful tools to assess the function of ectopically expressed proteins. However, it must be ensured that the protein of interest is functional in the host system and display native behaviour. In particular, mitochondrial uncoupling proteins (UCPs) displayed (non-native) artefactual uncoupling when expressed in yeast or can possess functions upon reconstitution in proteoliposomes that cannot be reproduced in isolated mitochondria. In the light of newly discovered UCP1 orthologues and paralogues (UCP2, UCP3, plant UCP), comparative functional studies require a system with identical mitochondrial, cellular, and genetic backgrounds. In this chapter, the protocols for the ectopic expression of mouse UCP1 in the human embryonic kidney (HEK293) cell line are introduced. In isolated cell culture mitochondria, the proton leak can be measured and modulators of UCP1 activity can be tested. As mouse UCP1 in this system shows native behaviour, this may be a suitable system to directly compare the functional relationships between different UCPs. PMID- 22057567 TI - Measurement of proton leak and electron leak in isolated mitochondria. AB - Oxidative phosphorylation is an important energy-conserving mechanism coupling mitochondrial electron transfer to ATP synthesis. Coupling between respiration and phosphorylation is not fully efficient due to proton and electron leaks. In this chapter, methods are presented to measure proton and electron leak activities in isolated mitochondria. The relative strength of a modular kinetic approach to probe oxidative phosphorylation is emphasised. PMID- 22057568 TI - Relation between mitochondrial membrane potential and ROS formation. AB - Mitochondria are considered as the main source of reactive oxygen species (ROS) in the cell. For this reason, they have been recognized as a source of various pathological conditions as well as aging. Chronic increase in the rate of ROS production is responsible for the accumulation of ROS-associated damages in DNA, proteins, and lipids, and may result in progressive cell dysfunctions and, in a consequence, apoptosis, increasing the overall probability of an organism's pathological conditions. The superoxide anion is the main undesired by-product of mitochondrial oxidative phosphorylation. Its production is triggered by a leak of electrons from the mitochondrial respiratory chain and the reaction of these electrons with O(2). Superoxide dismutase (MnSOD, SOD2) from the mitochondrial matrix as well as superoxide dismutase (Cu/ZnSOD, SOD1) present in small amounts in the mitochondrial intramembrane space, convert superoxide anion to hydrogen peroxide, which can be then converted by catalase to harmless H(2)O. In this chapter, we describe a relation between mitochondrial membrane potential and the rate of ROS formation. We present different methods applicable for isolated mitochondria or intact cells. We also present experiments demonstrating that a magnitude and a direction (increase or decrease) of a change in mitochondrial ROS production depends on the metabolic state of this organelle. PMID- 22057569 TI - Use of a calcium-sensitive electrode for studies on mitochondrial calcium transport. AB - Ca(2+)-sensitive electrode as a practical approach is used to follow Ca(2+) changes in the medium and particularly useful to study mitochondrial Ca(2+) uptake (or release); this method permits the continuous recording of Ca(2+) movements through the mitochondrial inner membrane. In this chapter, it is described how to prepare a Ca(2+)-sensitive electrode, and its application on mitochondrial studies with emphasis on the mitochondrial permeability transition. PMID- 22057570 TI - Imaging mitochondrial calcium signalling with fluorescent probes and single or two photon confocal microscopy. AB - The concentration of calcium ions in the mitochondria has a profound impact on mitochondrial function, modulating respiratory activity at physiological concentrations, while causing lethal damage during calcium overload. The "rhod" series of calcium sensitive fluorescent dyes tend to accumulate preferentially in mitochondria, although the reliability of mitochondrial calcium measurements depends critically on the partitioning of dye within the mitochondria which can vary between preparations. Methods are described to aid verification and quantification of the mitochondrial calcium concentration using single or two photon confocal microscopy and combining the imaging with another cytosolic calcium sensing dye. The method of linear unmixing to separate fluorescent signals based on either differing excitation or emission spectra is outlined and for the purposes of illustration is applied to the separation of rhod-2 signals originating from dye within the mitochondrial and nucleoli. PMID- 22057571 TI - Mitochondrial permeability transition pore and calcium handling. AB - Opening of a large conductance channel in the inner mitochondrial membrane, known as the mitochondrial permeability transition (MPT) pore, has been shown to be a primary mediator of cell death in the heart subjected to ischemia-reperfusion injury. Inhibitors of the MPT have been shown to reduce cardiac ischemia reperfusion injury. Furthermore, most cardioprotective strategies appear to reduce ischemic cell death either by reducing the triggers for the opening of the MPT, such as reducing calcium overload or reactive oxygen species, or by more direct inhibition of the MPT. This chapter focuses on key issues in the study of the MPT and provides some methods for measuring MPT opening in isolated mitochondria. PMID- 22057572 TI - Imaging of mitochondrial pH using SNARF-1. AB - Laser scanning confocal microscopy provides the ability to image submicron sections in living cells and tissues. In conjunction with pH-indicating fluorescent probes, confocal microscopy can be used to visualize the distribution of pH inside living cells. Here, we describe a confocal microscopic technique to image intracellular pH in living cells using SNARF-1, a ratiometric pH-indicating fluorescent probe. SNARF-1 is ester-loaded into the cytosol and mitochondria of adult cardiac myocytes. Using 568-nm excitation, emitted fluorescence longer and shorter than 595-nm are imaged and then ratioed after background subtraction. Ratio values for each pixel are converted to values of pH using a standard curve (lookup table). Images of the intracellular distribution of pH show cytosolic and nuclear areas to have a pH of ~7.1, but in regions corresponding to mitochondria, pH is 8.0, giving a mitochondrial DeltapH of 0.9. During hypoxia, mitochondrial pH decreases to cytosolic values, signifying the collapse of DeltapH. These results illustrate the ability of laser scanning confocal microscopy to image the intracellular distribution of pH in living cells and to determine mitochondrial DeltapH. PMID- 22057573 TI - Redox equivalents and mitochondrial bioenergetics. AB - Mitochondrial energy metabolism depends upon high-flux and low-flux electron transfer pathways. The former provide the energy to support chemiosmotic coupling for oxidative phosphorylation. The latter provide mechanisms for signaling and control of mitochondrial functions. Few practical methods are available to measure rates of individual mitochondrial electron transfer reactions; however, a number of approaches are available to measure steady-state redox potentials (E (h)) of donor/acceptor couples, and these can be used to gain insight into rate controlling reactions as well as mitochondrial bioenergetics. Redox changes within the respiratory electron transfer pathway are quantified by optical spectroscopy and measurement of changes in autofluorescence. Low-flux pathways involving thiol/disulfide redox couples are measured by redox western blot and mass spectrometry-based redox proteomics. Together, the approaches provide the opportunity to develop integrated systems biology descriptions of mitochondrial redox signaling and control mechanisms. PMID- 22057574 TI - NMR methodologies for studying mitochondrial bioenergetics. AB - Nuclear magnetic resonance (NMR) spectroscopy is a technique with an increasing importance in the study of metabolic diseases. Its initial important role in the determination of chemical structures (1, 2) has been considerably overcome by its potential for the in vivo study of metabolism (3-5). The main characteristic that makes this technique so attractive is its noninvasiveness. Only nuclei capable of transitioning between energy states, in the presence of an intense and constant magnetic field, are studied. This includes abundant nuclei such as proton ((1)H) and phosphorous ((31)P), as well as stable isotopes such as deuterium ((2)H) and carbon 13 ((13)C). This allows a wide range of applications that vary from the determination of water distribution in tissues (as obtained in a magnetic resonance imaging scan) to the calculation of metabolic fluxes under ex vivo and in vivo conditions without the need to use radioactive tracers or tissue biopsies (as in a magnetic resonance spectroscopy (MRS) scan). In this chapter, some technical aspects of the methodology of an NMR/MRS experiment as well as how it can be used to study mitochondrial bioenergetics are overviewed. Advantages and disadvantages of in vivo MRS versus high-resolution NMR using proton high rotation magic angle spinning (HRMAS) of tissue biopsies and tissue extracts are also discussed. PMID- 22057575 TI - Computational modeling of mitochondrial function. AB - The advent of techniques with the ability to scan massive changes in cellular makeup (genomics, proteomics, etc.) has revealed the compelling need for analytical methods to interpret and make sense of those changes. Computational models built on sound physico-chemical mechanistic basis are unavoidable at the time of integrating, interpreting, and simulating high-throughput experimental data. Another powerful role of computational models is predicting new behavior provided they are adequately validated.Mitochondrial energy transduction has been traditionally studied with thermodynamic models. More recently, kinetic or thermo kinetic models have been proposed, leading the path toward an understanding of the control and regulation of mitochondrial energy metabolism and its interaction with cytoplasmic and other compartments. In this work, we outline the methods, step-by-step, that should be followed to build a computational model of mitochondrial energetics in isolation or integrated to a network of cellular processes. Depending on the question addressed by the modeler, the methodology explained herein can be applied with different levels of detail, from the mitochondrial energy producing machinery in a network of cellular processes to the dynamics of a single enzyme during its catalytic cycle. PMID- 22057576 TI - Matriderm(r) 1 mm versus Integra(r) Single Layer 1.3 mm for one-step closure of full thickness skin defects: a comparative experimental study in rats. AB - PURPOSE: Dermal templates, such as Matriderm(r) and Integra(r), are widely used in plastic and reconstructive surgery, often as two-step procedures. A recent development is the application of thin dermal templates covered with split thickness skin grafts in one-step procedures. In this experimental study, we compare the two thin matrices Matriderm(r) 1 mm and Integra(r) Single Layer in a one-step procedure with particular focus on neodermis formation. METHODS: Matriderm(r) 1 mm and Integra(r) Dermal Regeneration Template-Single Layer (1.3 mm) were compared in a rat model. In three groups of five animals each, a full thickness wound was covered with (a) Matriderm(r) 1 mm and neonatal rat epidermis, (b) Integra(r) Single Layer and neonatal rat epidermis, or, (c) neonatal rat epidermis only (control). Histological sections 2 weeks post transplantation were analyzed with regard to take of template and epidermis, neodermal thickness, collagen deposition, vascularization, and inflammatory response. RESULTS: Take of both templates was complete in all animals. The Matriderm(r)-based neodermis was thinner but showed a higher cell density than the Integra(r)-based neodermis. The other parameters were similar in both matrices. CONCLUSION: The two templates demonstrate a comparable biological behavior early after transplantation. The only difference was found regarding neodermal thickness, probably resulting from faster degradation of Matriderm(r). These preliminary data suggest that both dermal templates appear similarly suitable for transplantation in a one-step procedure. PMID- 22057577 TI - Suitability of Soxhlet extraction to quantify microalgal Fatty acids as determined by comparison with in situ transesterification. AB - To assess Soxhlet extraction as a method for quantifying fatty acids (FA) of microalgae, crude lipid, FA content from Soxhlet extracts and FA content from in situ transesterification (ISTE) were compared. In most cases, gravimetric lipid content was considerably greater (up to sevenfold) than the FA content of the crude lipid extract. FA content from Soxhlet lipid extraction and ISTE were similar in 12/18 samples, whereas in 6/18 samples, total FA content from Soxhlet extraction was less than the ISTE procedure. Re-extraction of residual biomass from Soxhlet extraction with ISTE liberated a quantity of FA equivalent to this discrepancy. Employing acid hydrolysis before Soxhlet extraction yielded FA content roughly equivalent to ISTE, indicating that acidic conditions of ISTE are responsible for this observed greater recovery of FA. While crude lipid derived from Soxhlet extraction was not a useful proxy for FA content for the species tested, it is effective in most strains at extracting total saponifiable lipid. Lipid class analysis showed the source of FA was primarily polar lipids in most samples (12/18 lipid extracts contained <5% TAG), even in cases where total FA content was high (>15%). This investigation confirms the usefulness of ISTE, reveals limitations of gravimetric methods for projecting biodiesel potential of microalgae, and reinforces the need for intelligent screening using both FA and lipid class analysis. PMID- 22057578 TI - Two genetically related begomoviruses causing tomato leaf curl disease in Togo and Nigeria differ in virulence and host range but do not require a betasatellite for induction of disease symptoms. AB - Tomato leaf curl disease (ToLCD) has emerged as a major constraint on tomato production in some parts of West Africa. In this study, begomoviruses associated with ToLCD in Togo and Nigeria were characterized, as well as a betasatellite associated with the disease in Togo. The genome organization of both viruses is typical of Old World monopartite begomoviruses. Sequence analysis revealed that the begomovirus from Togo is a variant of tomato leaf curl Kumasi virus (ToLCKuV) from Ghana, and it is designated ToLCKuV-[Togo:Pagouda:2006] (ToLCKuV [TG:Pag:06]). The begomovirus from Nigeria has a recombinant genome, composed of sequences of ToLCKuV (major parent) and a cotton leaf curl Gezira virus (CLCuGV) like virus, and possesses an unusual non-reiterated replication-associated protein (Rep) binding site. Moreover, because the sequence has <89% identity with those of previously characterized begomoviruses, it is a new species and is designated tomato leaf curl Nigeria virus-[Nigeria:Odogbo:2006] (ToLCNGV [NG:Odo:06]). The cloned DNAs of ToLCKuV-TG and ToLCNGV were infectious and induced leaf curl symptoms in tomato plants, but ToLCNGV was comparatively more virulent. Both viruses also induced stunted growth and leaf curl symptoms in other solanaceous species (various Nicotiana spp. and Datura stramonium), whereas ToLCNGV but not ToLCKuV-TG induced symptoms in common bean plants. The betasatellite associated with ToLCD in Togo is genetically distinct (i.e., <78% nucleotide sequence identity with previously identified betasatellites) and is designated tomato leaf curl Togo betasatellite-[Togo:Pagouda:2006] (ToLCTGB [TG:Pag:06]). Replication and systemic spread of ToLCTGB in tomato was mediated by ToLCKuV-TG and ToLCNGV; however, the betasatellite had no effect on disease symptoms induced by either begomovirus. In contrast, ToLCTGB increased symptom severity induced by both viruses in Nicotiana spp. and D. stramonium. Thus, although ToLCTGB increased symptom severity in a host-dependent manner, it does not appear to play a role in ToLCD and may have been present with ToLCKuV-TG as a reassortant. PMID- 22057579 TI - Immunomodulatory effect of NSAID in geriatric patients with acute infection: effects of piroxicam on chemokine/cytokine secretion patterns and levels of heat shock proteins. A double-blind randomized controlled trial. (ISRCTN58517443). AB - Inflammation in older persons is associated with frailty, cachexia, and disability. We hypothesized that NSAID treatment in addition to antibiotics in older patients with acute infection might rapidly reduce inflammatory cytokines and might be of therapeutic potential to improve outcomes. A double-blind controlled trial was conducted in geriatric patients admitted for acute infection. Patients were randomized to receive either 10 mg piroxicam or placebo. Patients >=70 years with CRP levels >10 mg/L of acute infectious origin were eligible. Twenty-five cyto-/chemokines as well as heat shock proteins Hsp27 (HSPB1) and Hsp70 (HSPA1A) were measured the first 4 days and then weekly until discharge, with a maximum of 3 weeks. Thirty Caucasian patients were included (median age 84.5 years, 67% female, median CRP 87.5 mg/L). In the piroxicam group, IL-6 and IP-10/CXCL10 decreased significantly during the study period. Relationships between cytokines were disrupted in the piroxicam group: for 12 out of 20 cytokines the number of correlations between changes in serum levels was significantly lower compared to placebo. Serum Hsp70 levels decreased significantly in the piroxicam group, but not in the placebo group. Without heat challenge, intracellular levels of Hsp70 in monocytes decreased in both groups, whereas HsP27 in monocytes increased with piroxicam with a significant difference compared to placebo at 3 weeks. Piroxicam in this setting cannot be considered merely as an anti-inflammatory drug, but rather as an immunomodulator. Further studies are needed to establish whether these effects can change functional outcomes in geriatric patients. PMID- 22057580 TI - Subchondral bone density distribution in the human femoral head. AB - OBJECTIVE: This study aims to quantitatively characterize the distribution of subchondral bone density across the human femoral head using a computed tomography derived measurement of bone density and a common reference coordinate system. MATERIALS AND METHODS: Femoral head surfaces were created bilaterally for 30 patients (14 males, 16 females, mean age 67.2 years) through semi-automatic segmentation of reconstructed CT data and used to map bone density, by shrinking them into the subchondral bone and averaging the greyscale values (linearly related to bone density) within 5 mm of the articular surface. Density maps were then oriented with the center of the head at the origin, the femoral mechanical axis (FMA) aligned with the vertical, and the posterior condylar axis (PCA) aligned with the horizontal. Twelve regions were created by dividing the density maps into three concentric rings at increments of 30 degrees from the horizontal, then splitting into four quadrants along the anterior-posterior and medial-lateral axes. Mean values for each region were compared using repeated measures ANOVA and a Bonferroni post hoc test, and side-to-side correlations were analyzed using a Pearson's correlation. RESULTS: The regions representing the medial side of the femoral head's superior portion were found to have significantly higher densities compared to other regions (p < 0.05). Significant side-to-side correlations were found for all regions (r(2) = 0.81 to r(2) = 0.16), with strong correlations for the highest density regions. Side-to-side differences in measured bone density were seen for two regions in the anterio lateral portion of the femoral head (p < 0.05). CONCLUSIONS: The high correlation found between the left and right sides indicates that this tool may be useful for understanding 'normal' density patterns in hips affected by unilateral pathologies such as avascular necrosis, fracture, developmental dysplasia of the hip, Perthes disease, and slipped capital femoral head epiphysis. PMID- 22057581 TI - Evaluation of articular cartilage in patients with femoroacetabular impingement (FAI) using T2* mapping at different time points at 3.0 Tesla MRI: a feasibility study. AB - OBJECTIVES: To define the feasibility of utilizing T2* mapping for assessment of early cartilage degeneration prior to surgery in patients with symptomatic femoroacetabular impingement (FAI), we compared cartilage of the hip joint in patients with FAI and healthy volunteers using T2* mapping at 3.0 Tesla over time. MATERIALS AND METHODS: Twenty-two patients (13 females and 9 males; mean age 28.1 years) with clinical signs of FAI and Tonnis grade <= 1 on anterior posterior x-ray and 35 healthy age-matched volunteers were examined at a 3 T MRI using a flexible body coil. T2* maps were calculated from sagittal- and coronal oriented gradient-multi-echo sequences using six echoes (TR 125, TE 4.41/8.49/12.57/16.65/20.73/24.81, scan time 4.02 min), both measured at beginning and end of the scan (45 min time span between measurements). Region of interest analysis was manually performed on four consecutive slices for superior and anterior cartilage. Mean T2* values were compared among patients and volunteers, as well as over time using analysis of variance and Student's t-test. RESULTS: Whereas quantitative T2* values for the first measurement did not reveal significant differences between patients and volunteers, either for sagittal (p = 0.644) or coronal images (p = 0.987), at the first measurement, a highly significant difference (p <= 0.004) was found for both measurements with time after unloading of the joint. Over time we found decreasing mean T2* values for patients, in contrast to increasing mean T2* relaxation times in volunteers. CONCLUSION: The study proved the feasibility of utilizing T2* mapping for assessment of early cartilage degeneration in the hip joint in FAI patients at 3 Tesla to predict possible success of joint-preserving surgery. However, we suggest the time point for measuring T2* as an MR biomarker for cartilage and the changes in T2* over time to be of crucial importance for designing an MR protocol in patients with FAI. PMID- 22057582 TI - Risk factor profiles based on estimated glomerular filtration rate and dipstick proteinuria among participants of the Specific Health Check and Guidance System in Japan 2008. AB - BACKGROUND: Estimated glomerular filtration rate (eGFR) and albuminuria (proteinuria) are both important determinants of the risk of cardiovascular disease (CVD), end-stage renal disease (ESRD), and mortality. Few studies, however, have examined the risk factor profiles based on eGFR and proteinuria among the general population. METHODS: Data of the newly developed nationwide screening program of the Specific Health Check-up and Guidance System (Tokutei Kensin) initiated in 2008 were used in this study. The aim of this screening, targeting people 40-74 years of age, was to detect those with metabolic syndrome and to offer those services regarding lifestyle modifications that will lead to the reduction of diabetes mellitus (DM) and DM-related ESRD. Individual records of 580,000 participants in 69 cities and towns and 3 union cohorts throughout Japan were anonymously provided and included in the present study. RESULTS: Details of 332,174 participants (57.3% of the total) with both serum creatinine and dipstick urine test data were analyzed. Mean (SD) age was 63.6 (8.3) years and 40.6% were men. The mean (SD) eGFR was 75.0 (16.2) ml/min/1.73 m(2) and 5.4% had proteinuria. The prevalence of chronic kidney disease (CKD) stage 3, 4, and 5 was 14.2%, 0.2%, and 0.07%, respectively. The prevalence of DM, hypertension, and history of stroke and heart disease was correlated with the combination of eGFR and degree of proteinuria. CONCLUSION: The findings of the present study indicate that CKD and risk factors for CVD are quite common among middle-aged Japanese. CKD classification based on eGFR and proteinuria may be useful for predicting CVD, mortality rate, and ESRD in the Japanese population. PMID- 22057583 TI - Recent advances in the treatment of lupus nephritis. AB - Lupus nephritis is a common complication of systemic lupus erythematosus (SLE) which is associated with significant morbidity and mortality. The concept of two phases of therapy for lupus nephritis, such as an induction phase and a maintenance phase, is widely accepted. Since the renal involvement in SLE is heterogeneous, the treatment of lupus nephritis is governed by its pathological type and ranges from nonspecific measures, such as maintenance of adequate blood pressure control and blockade of the renin-angiotensin-aldosterone system, to the use of immunosuppressive agents. Cyclophosphamide (CYC) in combination with prednisone has been the standard method of treatment of the proliferative forms of lupus nephritis. However, the high rates of progression to end-stage renal disease coupled with the adverse effects of CYC and prednisone have led to an intensive search for more effective and less toxic therapies for lupus nephritis. We review the options available for the treatment of proliferative and membranous lupus nephritis and summarize the results of recently published clinical trials that add new perspectives to the management of kidney disease in SLE. PMID- 22057584 TI - Firewall function of the endothelial glycocalyx in the regulation of sodium homeostasis. AB - Plasma sodium, slightly above normal and in presence of aldosterone, stiffens vascular endothelium and reduces nitric oxide release with the consequence of endothelial dysfunction. This process is mediated by epithelial sodium channels (ENaC) and, most likely, the endothelial Na(+)/K(+)-ATPase. Both, ENaC and Na(+)/K(+)-ATPase, are located in the plasma membrane of endothelial cells and embedded in the endothelial glycocalyx (eGC). This negatively charged biopolymer is directly exposed to the blood stream and selectively buffers sodium ions. We hypothesize that the glycocalyx could interfere with endothelial sodium transport when extracellular sodium varies in the physiological range. Therefore, we modeled the endothelial cell as a pump-leak system measuring changes of intracellular sodium in cultured human endothelial cells. Experiments were performed under low/high extracellular sodium conditions before and after enzymatic eGC removal, and with inhibition of Na(+)/K(+)-ATPase and ENaC, respectively. Three major observations were made: (1) eGC removal by heparinase treatment facilitates sodium to enter/exit the endothelial cells. (2) The direction of net sodium movement across the endothelial plasma membrane depends on the concentration of extracellular sodium which regulates both the Na(+)/K(+) ATPase and ENaC activity. (3) Removal of eGC and inhibition of sodium transport modify the electrical resistance of endothelial cells. We conclude that the eGC serves as a potential "firewall" preventing uncontrolled access of sodium to the pump-leak system of the endothelial cell. After eGC removal, sodium access to the system is facilitated. Thus the pump-leak system could be regulated by ambient sodium and control vascular permeability in pathophysiological conditions. PMID- 22057585 TI - Purinergic activation of rat skeletal muscle membranes increases Vmax and Na+ affinity of the Na,K-ATPase and phosphorylates phospholemman and alpha1 subunits. AB - Muscle activity is associated with an increase in extracellular purines (ATP, ADP), which are involved in signalling mechanisms. The present study investigates the effect of purines on the function of Na,K-ATPase (Na,K-pump) in rat skeletal muscle. Na,K-ATPase activity was quantified by measuring the release of inorganic phosphate in the presence of ATP and variable Na(+) concentrations. In membranes purified from glycolytic muscle fibres, purinergic stimulation increases V (max) and decreases the K (m) (higher Na(+) affinity) of the Na,K-ATPase. Stimulatory effects were obtained using ATP, ADP, 2-methylthio-ADP and UPT, but not UDP and adenosine. The effect of ADP on V (max) can be inhibited by the non-specific P2Y receptor antagonists, suramin and PPADS. Moreover, the P2Y(13) receptor antagonist MRS 2211 strongly inhibited the response to ADP, whereas the specific P2Y(1) receptor antagonist MRS 2500 had less effect. Based on results from these agonists and antagonists, we conclude that P2Y(13) receptors mediate the main effects observed, that P2Y1 receptors are also involved and that some P2Y(2)/P2Y(4) receptors also appear to be involved. Receptor antagonists had no effect on ADP-induced subunit (phospholemman and alpha1) phosphorylation and changes in K (m) (Na(+) affinity). Thus, the stimulatory effects of purines are mediated by two independent mechanisms: P2Y receptor-mediated increase in Na,K ATPase capacity (increased V (max)) and P2Y receptor-independent phosphorylation of Na,K-ATPase phospholemman and alpha1 subunits, which induce changes in ion affinity. These mechanisms may contribute to up-regulation of Na,K-ATPase during muscle activity. PMID- 22057586 TI - Synthesis of 3-substituted 1,5-aldehyde esters via an organocatalytic highly enantioselective conjugate addition of new carbonylmethyl 2-pyridinylsulfone to enals. AB - A highly enantioselective organocatalytic protocol for conjugate addition of new nucleophilic carbonylmethyl 2-pyridinylsulfone to enals has been developed in good yields and with high enantioselectivities. The resulting Michael adducts are versatile building blocks for a variety of organic transformations. PMID- 22057587 TI - Carcinogenic potency of perfluorooctane sulfonate (PFOS) on Syrian hamster embryo (SHE) cells. AB - Perfluorooctane sulfonate (PFOS) is the degradation product of many fluoroderivatives and a widespread environmental contaminant. Its persistence, its long half-life in humans and its toxicity explain high concerns on human health side effects in future. PFOS is suspected to be a non-genotoxic carcinogen. In the present work, we assessed carcinogenic potential of PFOS by studying morphological transformation in Syrian hamster embryo (SHE) cells; cell transformation of SHE cells is an in vitro assay recommended by the Organization for Economic Cooperation and Development to detect carcinogens, genotoxic or not. Genotoxicity of PFOS and expression of PPARs genes in SHE cells were also measured. PFOS was shown to induce cell transformation (P < 0.05) at non cytotoxic concentrations (0.2 and 2 MUg/mL) (P <= 0.01). No genotoxic effect was recorded in the range of PFOS concentrations tested (2 * 10(-4) to 50 MUg/mL) using the single-cell gel electrophoresis (comet) assay after 5 and 24 h of exposure. The expression of PPARs genes was measured by qPCR within the first 24 h and after 7 days of PFOS treatment. Results indicated an increased expression of ppar-beta/delta isoform as early as 24 h. After 7 days, the increase of ppar beta/delta mRNA was significant at the concentrations inducing cell transformation (0.2 and 2 MUg/mL), while overexpression of ppar-gamma and ppar alpha did not closely relate to effective concentrations. The results indicate that PFOS behave as a non-genotoxic carcinogen and impacted PPARs genes. Its cell transforming potential paralleled an increased expression of ppar-beta/delta. PMID- 22057588 TI - Constraints for monocyte-derived dendritic cell functions under inflammatory conditions. AB - The activation of TLRs expressed by macrophages or DCs, in the long run, leads to persistently impaired functionality. TLR signals activate a wide range of negative feedback mechanisms; it is not known, however, which of these can lead to long-lasting tolerance for further stimulatory signals. In addition, it is not yet understood how the functionality of monocyte-derived DCs (MoDCs) is influenced in inflamed tissues by the continuous presence of stimulatory signals during their differentiation. Here we studied the role of a wide range of DC inhibitory mechanisms in a simple and robust model of MoDC inactivation induced by early TLR signals during differentiation. We show that the activation-induced suppressor of cytokine signaling 1 (SOCS1), IL-10, STAT3, miR146a and CD150 (SLAM) molecules possessed short-term inhibitory effects on cytokine production but did not induce persistent DC inactivation. On the contrary, the LPS-induced IRAK-1 downregulation could alone lead to persistent MoDC inactivation. Studying cellular functions in line with the activation-induced negative feedback mechanisms, we show that early activation of developing MoDCs allowed only a transient cytokine production that was followed by the downregulation of effector functions and the preservation of a tissue-resident non-migratory phenotype. PMID- 22057589 TI - Signal-pair correlation analysis of single-molecule trajectories. AB - There you go: How to get kinetic information from trajectories of single biomolecules? A method based on correlating signal ranges (here for a three-state DNA hairpin with F = folded, I = intermediate, and U = unfolded state) is reported and shows how to get the kinetic scheme and the corresponding rates, even for states with low occupancy or very short lifetime, states which overlap because of noise, and systems with very similar or very different rates. PMID- 22057590 TI - Prospective evaluation of unidirectional barbed suture for various indications in surgeon-controlled robotic reconstructive urologic surgery: Wake Forest University experience. AB - PURPOSE: To evaluate the usage of unidirectional barbed suture and its related implications in various surgeon-controlled robotic reconstructive urologic surgeries. METHODS: From March 2010 to March 2011, all patients undergoing various surgeon-controlled robotic reconstructive urologic surgeries utilizing barbed sutures were prospectively enrolled in this study. Type and number of procedure performed were noted. Intraoperative and peri-operative outcomes potentially related to suture technique and material were recorded. RESULTS: This study reports on 210 patients, in whom barbed suture was used during this period. These included partial nephrectomy (20), pyeloplasty (9), ureteric tailoring and reimplantation (1), closure of bladder after Nephroureterectomy with excision of bladder cuff (8), closure of vaginal cuff in female radical cystectomy (12), partial cystectomy (1), radical prostatectomy (152), simple prostatectomy (2), vesicovaginal fistula repair (3), sacrocolpopexy (1), and hernia repair (1). We encountered 5 instances (2.38%) of tissue cut through possibly attributable to the use of barbed suture and 4 instances of misplacement of suture occurred, of these two required a new suture, whereas retrograde pull back of suture and needle was performed in 2 cases. No instance of slip back/loosening of suture was noted once it was tightened. At mean follow-up of 6.8 (1-14 months) months, we did not encounter any complications of urinary leakage, stone formation or fistula or any clinical evidence of urinary tract obstruction due to the use of barbed suture. CONCLUSION: Use of unidirectional barbed suture is safe, feasible, and efficient at short-term follow-up for reconstructive part of urological procedures. PMID- 22057591 TI - Failure of polymyxin B and fosfomycin combination to eradicate extensively antibiotic Klebsiella pneumoniae from the urine despite in-vitro activity. PMID- 22057592 TI - Can Feldenkrais exercises ameliorate subclinical depressive symptoms in older adults? A pilot study. PMID- 22057593 TI - Interprofessional team practices, attitudes, and educational experiences of medical faculty. PMID- 22057594 TI - Vitamin D deficiency assessment in a rural, Hispanic community in South Carolina. PMID- 22057595 TI - A first-principles theoretical approach to heterogeneous nanocatalysis. AB - A theoretical approach to heterogeneous catalysis by sub-nanometre supported metal clusters and alloys is presented and discussed. Its goal is to perform a computational sampling of the reaction paths in nanocatalysis via a global search in the phase space of structures and stoichiometry combined with filtering which takes into account the given experimental conditions (catalytically relevant temperature and reactant pressure), and corresponds to an incremental exploration of the disconnectivity diagram of the system. The approach is implemented and applied to the study of propylene partial oxidation by Ag(3) supported on MgO(100). First-principles density-functional theory calculations coupled with a Reactive Global Optimization algorithm are performed, finding that: (1) the presence of an oxide support drastically changes the potential energy landscape of the system with respect to the gas phase, favoring configurations which interact positively with the electrostatic field generated by the surface; (2) the reaction energy barriers for the various mechanisms are crucial in the competition between thermodynamically and kinetically favored reaction products; (3) a topological database of structures and saddle points is produced which has general validity and can serve for future studies or for deriving general trends; (4) the MgO(100) surface captures some major features of the effect of an oxide support and appears to be a good model of a simple oxide substrate; (5) strong cooperative effects are found in the co-adsorption of O(2) and other ligands on small metal clusters. The proposed approach appears as a viable route to advance the role of predictive computational science in the field of heterogeneous nanocatalysis. PMID- 22057596 TI - n-Doping of organic electronic materials using air-stable organometallics. AB - Air-stable dimers of sandwich compounds including rhodocene and (pentamethylcyclopentadienyl)(arene)ruthenium and iron derivatives can be used for n-doping electron-transport materials with electron affinities as small as 2.8 eV. A p-i-n homojunction diode based on copper phthalocyanine and using rhodocene dimer as n-dopant shows a rectification ratio of greater than 10(6) at 4 V. PMID- 22057597 TI - Kikuchi-Fujimoto disease. Histiocytic necrotizing lymphadenitis. AB - Kikuchi-Fujimoto disease (KFD), or histiocytic necrotizing lymphadenitis, is a self-limited disease of complex and unclear etiology. Clinically and microscopically, it may mimic malignant lymphoma and other non-malignant diseases. Recognition of this entity is crucial, as mistaking this disease as lymphoma has major clinical consequences. Although KFD is a well-recognized entity in the literature, many clinicians and pathologists are still unaware of its existence. In this article, a review of KFD is provided with special emphasis on the pathogenesis and pathological differential diagnosis of this disease. PMID- 22057598 TI - In vitro efficacy of acetohydroxyacid synthase inhibitors against clinical strains of Mycobacterium tuberculosis isolated from a hospital in Beijing, China. AB - OBJECTIVE: To assess the efficacy of acetohydroxyacid synthase (AHAS) inhibitors against Mycobacterium tuberculosis from China, including multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains. METHODS: In this study, the tube dilution method and Middlebrook 7H10 agar media were used to describe the in vitro efficacy of 3 AHAS inhibitors (sulfometuron methyl, monosulfuron, and monosulfuron-ester) against H37Rv and 26 clinical isolates, which include MDR-TB and XDR-TB strains, from the 309th Hospital of Chinese People's Liberation Army (PLA 309), Beijing, China. Cytotoxity of these compounds were then evaluated using the 3-[4,5 dimethylthiazol-2yl]-2,5-dipheny tetrazolium bromide assay with HBE cells. All the experiments were performed from January 2010 to November 2010 in the Department of Clinical Laboratory of the PLA 309 hospital. RESULTS: Sulfometuron methyl (minimum inhibitory concentration [MIC] range, 8-16 mg/L), monosulfuron ester (MIC range, 8-16 mg/L), and monosulfuron (MIC range, 16-64 mg/L) showed significant activity against all Mycobacterium tuberculosis strains tested in this study in vitro, and they exhibited the same degree of activity against MDR and XDR isolates with that shown against the susceptible strains. All 3 compounds showed little cytotoxicity, with an IC50 against HBE cells greater than 300 mg/L. CONCLUSION: The results suggest that AHAS could serve as a target protein for the development of novel anti-TB therapeutics in China. PMID- 22057599 TI - Use of laryngeal mask airway in anesthesia for treatment of retinopathy of prematurity. AB - OBJECTIVE: To review clinical experience of anesthesia management using laryngeal mask airway (LMA) during retinopathy of prematurity (ROP) photocoagulation. METHODS: After obtaining the ethical approval from the Ethics Committee, we retrospectively reviewed the anesthesia records of 85 infants who underwent laser photocoagulation for ROP between June 2004 and June 2010 at the Department of Anesthesiology and Intensive Care, School of Medicine, Dokuz Eylul University, Izmir, Turkey. Anesthesia records were reviewed for airway management and respiratory complications in addition to medical and demographic data. RESULTS: The mean gestational age was 28.61+/-2.62 weeks, birth weight was 1205.24+/ 384.51 g, post-conceptional age was 38.21+/-7.01 weeks, and weight at the time of operation was 2323.9+/-588.6 g. Laryngeal mask airway was used with minimal complications in all patients, even in patients with chronic lung disease including bronchopulmonary dysplasia. After the ROP treatment, the LMA was successfully removed in all infants under deep anesthesia and none of the patients needed endotracheal intubation or ventilatory support. CONCLUSION: Laryngeal mask airway is a safe and easy to use alternative for airway management during laser photocoagulation procedure in infants with ROP. PMID- 22057600 TI - Significance of serum total prostate specific antigen and digital rectal examination in the diagnosis of prostate cancer. AB - OBJECTIVE: To assess the significance of serum total prostate specific antigen (tPSA) and digital rectal examination (DRE) in the diagnosis of prostate cancer (PC). METHODS: One hundred and eighteen patients with serum tPSA ranging between 2.5 and 10 ng/ml with lower urinary tract symptoms presented at the Urology Clinic of Soba University Hospital, Khartoum, Sudan from August 2008 and January 2010 were included in the study. Serum tPSA was measured using enzyme immunoassay method, and accordingly, the patients were classified into 2 groups: patients that had tPSA between 2.5-4.0 ng/ml; and patients that had tPSA between 4.1-10 ng/ml. The DRE was performed on all patients by a qualified urologist, and were recorded as a group with suspicion of PC, and a group with no suspicion of PC. All patients underwent transrectal sextant prostate biopsy. RESULTS: The DRE alone showed 63.8% sensitivity and 68% specificity with 46.9% positive predictive value (PPV) for the diagnosis of PC. The tPSA test revealed 91.6% sensitivity and 24% specificity with PPV of 34%. However, when combining DRE and tPSA, the sensitivity reached 100% and the specificity increased to 92% with PPV of 49%. CONCLUSION: Combining DRE and tPSA test increases the sensitivity, specificity, and PPV of PC detection. PMID- 22057601 TI - The incidence and spectrum of central nervous system malformations in newborns over a decade (2001-2010) in the Central Region of Saudi Arabia. AB - OBJECTIVE: To study the incidence and spectrum of central nervous system (CNS) malformations confirmed by computerized tomography (CT), or magnetic resonance imaging (MRI) in a Saudi newborn population of Riyadh over a 10-year period, and to compare our findings with those in the published literature. METHODS: This is a retrospective analysis of prospectively collected data on all inborn babies admitted to the Neonatal Intensive Care Unit in Riyadh Military Hospital, Riyadh, Kingdom of Saudi Arabia that underwent CT or MRI of the brain and spine from January 2001 to December 2010. Out born babies, babies who sustained birth asphyxia, and premature babies were excluded from the study. RESULTS: During the study period, 849 imaging studies were carried out, and from these 248 babies with CNS malformations were identified. Specific syndromes associated with CNS malformations occurred in 58 (23.4%). Dysraphism was found in 42 babies (16.9%) (25 spinal and 17 cranial). Hydrocephalus was present in 30 (12.1%), cortical malformations occurred in 31 (12.5%), which was dominated by abnormal cell migration in 20. Cerebellar and posterior fossa abnormalities were diagnosed in 44 (17.7%), Dandy-Walker syndrome in 15, and Joubert syndrome in 12. Prosencephalic pathology was seen in 39 (15.7%), commissural abnormalities in 29, while there was holoprosencephaly in 12. Vascular malformations were found in 4 babies (1.4%). CONCLUSION: This study showed a wide spectrum of malformations, with all CNS malformations confirmed by advanced imaging techniques. PMID- 22057602 TI - Normal knee angles in the adult Saudi population. AB - OBJECTIVE: To study knee angles in the adult Saudi population and compare their values to the published data from other populations. METHODS: Antero-posterior bilateral radiographs of 333 normal knees of 120 males and 213 females, with age range of 18-65 years, were studied retrospectively at King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from January 2009 to December 2009. Tibiofemoral (TFA), lateral distal femoral (LDFA), and lateral proximal tibial (LPTA) angles were measured and the mean of each angle was calculated. The relationship between each angle and age, gender, and side of the body was tested, and compared with the international figures. RESULTS: The mean for TFA in Saudis was 174.41 degrees , LDFA was 90.07 degrees and LPTA was 89.42 degrees . All angles were not significantly related to gender. Significant relations existed between TFA and side of the body, and between LDFA and age. Variations in means and ranges of knee angles between the Saudi and other populations were determined. A significant difference existed between means of TFA, LDFA, and LPTA of Saudis and those of Caucasians, between mean of TFA of Saudis and that of Chinese, and between mean of LPTA of Saudi males and that of Chinese males. The means of TFA of selected age groups in Saudis differed significantly when compared to those in the corresponding age groups in Japanese and Australian Caucasians. CONCLUSION: Knee angles are like many other skeletal angles that may have ethnic variation between different populations. The study reinforces the need for reference values of knee angles in a given population. PMID- 22057603 TI - Venous thromboembolism risk and prophylaxis in a Saudi hospital. AB - OBJECTIVE: To evaluate the risk factors and physician's compliance to American College of Chest Physicians (ACCP) guidelines recommendations for venous thromboembolism (VTE) prevention at our hospital. METHODS: This retrospective cohort study was conducted at King Abdulaziz Hospital, Al-Ahsa, Saudi Arabia from November 2009 to December 2009. We used the American College of Chest Physicians (ACCP) 2008 guidelines and Caprini's scores to assess VTE risk and to determine whether patients had received recommended prophylaxis. All hospital in-patients aged 15 years or above were assessed for risk of VTE by reviewing the hospital chart. A data sheet was developed to obtain the data on demographics, VTE prophylaxis medication, dose, route, duration, and associated risk factors. The primary endpoint was the rate of appropriate thromboprophylaxis. RESULTS: Nine hundred and sixty-eight patients were included. The mean age was 40 +/- 18.7 years, and 647 (66.8%) were women. According to the ACCP criteria, 547 (56.5%) patients were at risk for VTE. Of 210 patients that qualified for prophylaxis, 117 (55.7%) received some form of prophylaxis. However, 46 (39.3%) of them received ACCP-recommended VTE prophylaxis. In contrast, 25.6% of patients with no risk, according to Caprini score, had thromboprophylaxis prescribed. CONCLUSION: This study demonstrates that only a small proportion of eligible patients received the recommended VTE prophylaxis. Efforts should be made to develop strategies to improve patient safety practices. PMID- 22057604 TI - Knowledge, attitudes, and practices regarding cervical cancer screening among physicians in the Western Region of Saudi Arabia. AB - OBJECTIVE: To evaluate knowledge and practice of the Pap test, the role of HPV in the etiology of cervical cancer, and attitudes regarding the HPV vaccine of female physicians in the Western Region of Saudi Arabia. METHODS: A cross sectional descriptive study using an interview with a structured questionnaire to obtain information regarding cervical cancer, practice in screening for cervical cancer, and attitudes of female physicians regarding the HPV vaccine in different health facilities in Saudi Arabia. The study was performed in the Department of Obstetrics and Gynecology, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia, between May and December 2009. RESULTS: Of the 200 respondents, 70 (35%) physicians comprised gynecological doctors (GDs) group I, and 130 (65%) physicians comprised the non-gynecological doctors (NGDs) group II. The mean age was 36 years. A total of 63 (90%) in group I, and 87 (60.5%) in group II knew that HPV is a cause for cervical cancer. Forty five (64.3%) in group I, and 44 (33.8%) in group II believed that cervical cancer was curable (p<0.05). A total of 182 (91%) physicians in the GDs and NGDs group knew that the Pap smear test is used as a screening method for cervical cancer. A total of 97 (48.5%) physicians knew about the HPV vaccine. When the physicians were provided with information regarding the HPV vaccine, 100 (50%) physicians stated they would recommend the vaccine to their patients. CONCLUSION: Physicians in Saudi Arabia would benefit from further education regarding the available screening, prevention for HPV, and cervical cancer. PMID- 22057605 TI - Awareness of healthcare workers regarding preventive measures of communicable diseases among Hajj pilgrims at the entry point in Western Saudi Arabia. AB - OBJECTIVE: To determine the level of knowledge of healthcare workers (HCWs) towards preventive measures for communicable diseases among pilgrims, and to highlight the difficulties faced by HCWs in implementing preventive measures at entry point. METHODS: A cross-sectional study was conducted at King Abdulaziz International Airport Hajj Terminals in Jeddah, Kingdom of Saudi Arabia during Hajj season from October to November 2009 including 325 healthcare workers (HCWs). Data were collected using a self-administered questionnaire. RESULTS: Difficulties reported by HCWs were refusal of vaccine, or chemoprophylaxis by some pilgrims, language barriers, and difficulties in organizing pilgrims. The different items related to meningococcal meningitis were answered correctly by most HCWs except for preventive measures applied to infants and children. Less than one half were aware of the period of validity for Yellow Fever vaccine certificate and measures to be taken for unvaccinated pilgrims. Only 32.9% were aware of preventive measures that should be applied against influenza A (H1N1). Physicians, those reading guidelines, and those with high experience a showed significantly better level of knowledge than other categories. CONCLUSION: The HCWs have difficulties in some preventive measures, especially among non physicians, those with less years of experience, and those who did not read the written guidelines, which highlighted the importance of training courses before Hajj season. PMID- 22057606 TI - Study of risky behaviors leading to unintentional injuries among high school students in Tehran, Iran. AB - OBJECTIVE: To determine risky behaviors leading to unintentional injuries among Tehrani high school students in 2009. METHODS: This cross-sectional study was carried out berween October and December 2009. Out of 237,300 (185151 governmental, 52149 non governmental) Tehrani high school students in both genders, 727 subjects were selected by multistage randomized sampling. Among 20 education districts, 8 districts were selected and divided by stratified sampling into 3 areas: North, Center, and South. Data were collected by cluster random sampling in each district using the standard questionnaire of the Management Diseases Center of America, which had been validated in Iran. Subjects were healthy students aged 12-18 years. Risky behaviors including fall, burn, poisoning, and road traffic injuries were studied. RESULTS: The mean age of subjects was 16.8+/-1.2, range 12-18 years. Overall, 44% of boys and 38% of girls were exposed to risky behaviors leading to unintentional injuries. Significant differences were observed in driving without licence among boys and in governmental schools (p=0.000). Using a motorcycle was more prevalent in the south of Tehran (p=0.000). Significant differences were observed among boys related to poisoning substance exposure, driving without a licence, motorcycle driving, and non-helmet use during motorcycle driving (p=0.000). CONCLUSION: Approximately half of the boys and more than one-third of the girls were exposed to risky behaviors leading to unintentional injuries. Prevention of unintentional injuries caused by children's risky behaviors is crucial, particularly among boys and those from deprived areas. PMID- 22057607 TI - Comparison of jeopardy game format versus traditional lecture format as a teaching methodology in medical education. AB - OBJECTIVE: To compare students' performance, satisfaction, and retention of knowledge between a 'jeopardy game format' and a 'didactic lecture format' in teaching viral exanthema to fifth-year medical students. METHODS: We conducted a parallel-group randomized controlled trial in the Department of Pediatrics, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia from November 2008 to January 2009. We randomized fifth-year medical students into 2 groups. We taught viral exanthema to group one in lecture format, while group 2 received the same instruction in a jeopardy style game format. Both groups underwent a pretest, post-test I, and satisfaction survey. We conducted post-test II after 2 months to assess the retention of knowledge. The satisfaction survey consisted of 5 questions using a 5 point Likert scale. We used the paired sample t-test, and independent sample t-test to compare the results. RESULTS: Eighty-two students participated in the study (41 in each group). Both groups showed significant improvement in their knowledge on the post-test I compared with the pre-test scores. However, the post-test II conducted after 2 months showed that retention of knowledge was significantly better in the game format. The satisfaction survey showed that the game format was more enjoyable and fun. CONCLUSION: The game format teaching strategy has an added advantage in retaining knowledge of the subject for a longer time compared with a lecture format. PMID- 22057608 TI - Characterization of Yemeni patients treated for oral and pharyngeal cancers in Saudi Arabia. AB - OBJECTIVE: To determine the relative frequency and rank of oral cancer (OC) and pharyngeal cancer (PC) among Yemeni cancer patients who were treated and registered in the Kingdom of Saudi Arabia (KSA) over 14 years, and to characterize these patients by different grouping factors. METHODS: In this retrospective study, the Saudi Cancer Registry, Riyadh, KSA officially provided the data regarding all Yemeni patients registered between 1994 and 2007. These data were reclassified and analyzed to present the cancer distribution by the main sites adopted by Globocan 2008. The OC and PC patients were statistically described and analyzed according to the demographic data and tumor details. This study was conducted at the Oral Medicine, Medically Compromised and Research Clinic, Department of Dentistry, Riyadh Military Hospital, Saudi Arabia between January and April 2011. RESULTS: There were 5862 Yemenis registered with malignancies. The OC ranked the eighth most common malignancy (215, 3.7%) with 1.65:1 male to female ratio, whereas PC ranked the seventh (245, 4.2%) with 2.06:1 male to female ratio. The most affected oral sub-site was the tongue (91, 42.3%) while the nasopharynx accounted for 79% (194) of PC. The PC patients were significantly younger than those with OC (45.88+/-16.72 versus 55.6+/-15.75). The squamous cell carcinoma was the most frequent morphological type (289, 63.5%) but significantly more frequent in OC. Approximately 56% (255 patients) were diagnosed at advanced stage, however, significantly more frequent in PC (155, 64.6%). CONCLUSION: The relative frequencies of oral and pharyngeal cancers in Yemen are quite high. The demographic and tumor characteristics of these cancers are obviously different. PMID- 22057609 TI - Photodynamic therapy as an adjunctive to scaling and root planing in treatment of chronic periodontitis in smokers. AB - OBJECTIVE: To compare photodynamic therapy (PDT) as an adjunctive treatment of chronic periodontitis with scaling and root planing (Sc/Rp) in smokers. METHODS: This is a split-mouth, single-masked randomized controlled clinical trial conducted at the Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia between May 2010 and March 2011. Fifty-four teeth with probing depth of >=5mm at one or more periodontal sites in 20 smokers diagnosed with moderate to severe chronic periodontitis were selected. In each patient, at least one tooth was randomly assigned to Sc/Rp plus PDT (test group) and the contra-lateral tooth was assigned to Sc/Rp only (control). Plaque index (PI), bleeding on probing (BOP), probing depth (PD), recession and clinical attachment level (CAL) were recorded at baseline and 3 months after the periodontal treatment. Descriptive statistics and Wilcoxon signed ranked test were used for data analysis. RESULTS: There was a statistically significant improvement in PD, CAL, BOP, and PI after periodontal treatment in both groups. No statistically significant differences between the 2 groups in any of the periodontal parameters were found at baseline (p>0.05), but a statistically significant greater reduction in PD (p=0.028) and CAL (p=0.044) in the test compared to the control group was found at the 3-month follow up. CONCLUSION: Photodynamic therapy might have an additional benefit to scaling and root planing when treating smokers affected with periodontitis. PMID- 22057610 TI - Biliopleural fistula with cholethorax. A rare complication of percutaneous transhepatic biliary drainage. AB - Biliopleural fistula leading to cholethorax formation is a rare complication of percutaneous transhepatic cholangiography (PTC). Ideally it should be treated conservatively as it closes spontaneously in most patients. However, in complicated cases it may require surgical intervention. We report a 35-year-old male with right biliopleural fistula with cholethorax following PTC. The patient complained of shortness of breath, right pleuritic chest pain, and cough after removal of PTC catheter. Chest radiograph showed an extensive right pleural effusion. The diagnosis was confirmed by drainage of dark green pleural fluid with high bilirubin content. The initial treatment with chest tube and drainage was unsuccessful. He underwent video assisted thoracoscopic intervention. Diagnostic modalities and management options for biliopleural fistula are discussed along with a review of literature. PMID- 22057611 TI - Hemangiopericytoma of the adult male breast. AB - Hemangiopericytoma (HPC) is a rare tumor originated from the vascular pericytes, and it is uncommon in the breast. Only 2 cases of HPC in the male breast have been reported in the literature. This report presents a case of a 24-year-old man with a mass in his right breast. Under local anesthesia, the tumor was excised and diagnosed as 'malignant tumor of the breast, perhaps originated from the vessel tissues' based on pathological examination. Finally, a modified radical mastectomy and an axilla fossa sampling were performed, and 4 lymph nodes showed symptoms of reactive hyperplasia. We followed the patient without any treatment and no local recurrence or metastasis has been observed. We also review the literature and discuss the characteristics, immuno-phenotype, and prognosis of HPC. The accurate diagnosis of HPC depends on the appropriate histological and immunohistochemical examination. PMID- 22057612 TI - Dose-dependent profile of ethanolic extracts of Iranian propolis on radiation induced mucositis in rats. PMID- 22057613 TI - Insulin-like growth factor-I gene poly-morphisms and left ventricular function in Turkish obese women with insulin resistance. PMID- 22057614 TI - Tumor necrosis factor-receptor 2 and TROY gene expression patterns in cutaneous squamous cell carcinoma in a Tunisian population. PMID- 22057615 TI - An infant with renal and hepatic cysts. PMID- 22057616 TI - HBeAg negativity is not equal to the presence of pre core mutations in chronic hepatitis B patients. PMID- 22057617 TI - Incidence of cleft lip and palate in Iran. A meta-analysis. PMID- 22057618 TI - New and known mutations associated with inborn errors of metabolism in a heterogeneous Middle Eastern population. PMID- 22057619 TI - Prevalence of IgG antibodies against Toxoplasma gondii among Syrian females of childbearing age. PMID- 22057620 TI - Vitamin D levels in Saudi children with type 1 diabetes. PMID- 22057621 TI - Abdominal compartment syndrome in childhood: the role of near infrared spectroscopy for the early detection of the organ dysfunction. PMID- 22057622 TI - Adolescent substance misuse: neurobiology and evidence-based interventions. AB - This chapter reviews empirical research on risk-factors for adolescent onset of substance use and misuse, with a particular focus on a recent body of literature aimed at understanding the link between early onset substance use, neuropsychological impairment and future addiction risk. The evidence suggests a causal pathway with some studies showing that adolescents might be more sensitive to the neurotoxic effects of substances, which contributes to their heightened addiction vulnerability. While questions remain pertaining to the extent to which cognitive precursors to early onset substance use account for these impairments, the evidence from a few studies suggests that early substance misuse produces some cognitive or emotional processing impairment beyond these premorbid deficits. The possible interaction between premorbid deficits and the effects of substance use on cognitive development might also explain why early onset substance use so rapidly spirals into substance abuse and dependence and provides a strong rationale for preventing early onset substance use, particularly among those at risk. This chapter then reviews the different approaches to drug and alcohol prevention, the evidence-base for current programs and the essential intervention components that lead to beneficial outcomes and high implementation fidelity. PMID- 22057623 TI - Pharmacological MRI approaches to understanding mechanisms of drug action. AB - Functional neuroimaging is a novel technique for the study of drug action in the brain. The emerging role of this method is intimately tied to the unique challenges to advancing drug development for neuropsychiatric disorders. This chapter first presents a brief overview of the important treatment needs that remain to be met, which serve as clinical targets for drug development. Important factors that hinder progress in drug development, which arise from clinical, scientific and economic issues, are acknowledged. This sets the stage for the unique advantages of functional neuroimaging modalities such as functional MRI (fMRI) as a biomarker and drug development tool, in both clinical and preclinical phases. The physiological basis of the fMRI signal is briefly outlined, and aspects of neural signaling related to this signal change, with emphasis on implications for pharmacology studies. The utility of fMRI for evaluating the full anatomic extent of central neurotransmitter systems in a dynamic manner is then described. This is a critical advantage, and particularly important for studies of how systems such as the monoamines modulate distributed neural networks during cognitive processes in both health and illness, and how these actions are modified with pharmacological intervention. Central catecholamine systems are seen as paradigmatic targets amenable to pharmacologic fMRI. fMRI is observed to occupy a unique position in the armamentarium of methods available to the pharmacologist and the drug development process, and poised to play an expanding role in basic and clinical neuroscience. PMID- 22057624 TI - Indeterminate 1-2-cm nodules found on hepatocellular carcinoma surveillance: biopsy for all, some, or none? AB - In the latest hepatocellular carcinoma (HCC) management guidelines by the American Association for the Study of Liver Diseases, biopsy is advocated for all nodules deemed indeterminate after imaging work-up by contrast-enhanced scans. However, the latest guidelines' imaging work-up algorithm has been shown to improve sensitivity of characterization of HCC for 1-2-cm nodules, decreasing the proportion of HCCs that remain indeterminate after imaging work-up. We undertook a study of 1-2-cm indeterminate nodules to determine what proportions are malignant and which variables can be used to limit biopsy to a subset of nodules at higher risk of malignancy. Eighty consecutive patients with 93 indeterminate nodules were included. Final diagnosis was established in 85 nodules, with 13 malignant (9 by biopsy, 4 by growth) and 72 benign (stability of >=18 months). Cause of liver disease, ethnicity, size, arterial hypervascularity, venous hypoenhancement, and presence of synchronous typical HCC were analyzed by univariate logistic analysis to determine significant predictors of malignancy. Rate of malignancy among indeterminate 1-2-cm nodules was found to be 14%-23%. Only arterial hypervascularity [odds ratio (OR), 3.7) and presence of synchronous HCC (OR, 7.1) were significant predictors of malignancy. A strategy of limiting biopsy to nodules that had either feature would result in 23 biopsies and potentially detect 8 of 13 malignant nodules, yielding a sensitivity of 62% and specificity of 79%. CONCLUSION: The prevalence of malignancy among 1-2-cm indeterminate nodules is low (14%-23%), and biopsy of all such nodules results in many negative results. Limiting biopsy to nodules with arterial hypervascularity or in the presence of a synchronous typical HCC would detect the majority of HCCs while substantially reducing the number of biopsies. PMID- 22057625 TI - Floral ontogeny in Astragalus compactus (Leguminosae: Papilionoideae: Galegeae): variable occurrence of bracteoles and variable patterns of sepal initiation. AB - Comparative studies of floral ontogeny represent a growing field that promise to provide new insights on floral evolution. Floral ontogenetic information has been used successfully in Leguminosae for re-examining phylogenetic relationships at different levels. Using epi-illumination light microscopy, we present original ontogenetic data in Astragalus compactus, which was chosen because of its unusual arrangement of inflorescence and variable occurrence of bracteoles on flowers. Based on our results, uncommon ontogeny of the inflorescence led to the arrangement of flowers in four different positions. Variation was observed not only in the presence of bracteoles, but also in the order of sepal initiation in flowers of the same inflorescence. Surprisingly, besides the widely stated unidirectional pattern, bidirectional, sequential and an atypical unreported order were observed. High degree of overlapping between whorls and formation of two types of common primordia also were found. The variable occurrence of bracteoles suggests that the species is in an intermediate state towards fully lacking of bracteoles. We propose that the variability of the sequence of sepal initiation is possibly a consequence of the function of mechanical forces generated by surrounding leaves. Relationships between mechanical force and auxin signalling are discussed. PMID- 22057626 TI - Phosphate ligands in the gold(I)-catalysed activation of enynes. AB - Gold(I) forms neutral complexes with binol phosphates that are unreactive in the catalytic cyclisation of enynes. Reaction in protic solvents or activation by silver(I) restores the catalytic activity. PMID- 22057627 TI - Changes observed in radionuclide bone scans during and after teriparatide treatment for osteoporosis. AB - PURPOSE: Visual changes on radionuclide bone scans have been reported with teriparatide treatment. To assess this, serial studies were evaluated and quantified in ten postmenopausal women with osteoporosis treated with teriparatide (20 MUg/day subcutaneous) who had (99m)Tc-methylene diphosphonate (MDP) bone scans (baseline, 3 and 18 months, then after 6 months off therapy). METHODS: Women were injected with 600 MBq (99m)Tc-MDP, and diagnostic bone scan images were assessed at 3.5 h. Additional whole-body scans (10 min, 1, 2, 3 and 4 h) were analysed for (99m)Tc-MDP skeletal plasma clearance (K(bone)). Regional K(bone) differences were obtained for the whole skeleton and six regions (calvarium, mandible, spine, pelvis, upper and lower extremities). Bone turnover markers (BTM) were also measured. RESULTS: Most subjects showed visual changes on 3- and 18-month bone scan images that disappeared after 6 months off therapy. Enhanced uptake was seen predominantly in the calvarium and lower extremities. Whole skeleton K(bone) displayed a median increase of 22% (3 months, p = 0.004) and 34% (18 months, p = 0.002) decreasing to 0.7% (6 months off therapy). Calvarium K(bone) changes were three times larger than other sites. After 6 months off therapy, all K(bone) and BTM values returned towards baseline. CONCLUSION: The increased (99m)Tc-MDP skeletal uptake with teriparatide indicated increased bone formation which was supported by BTM increases. After 6 months off therapy, metabolic activity diminished towards baseline. The modulation of (99m)Tc-MDP skeletal uptake during treatment was the result of teriparatide's metabolic activity. These findings may aid the radiological evaluation of similar teriparatide patients having radionuclide bone scans. PMID- 22057628 TI - Molecular characterization of a genomic interval with highly uneven recombination distribution on maize chromosome 10 L. AB - Homologous recombination in meiosis provides the evolutionary driving force in eukaryotic organisms by generating genetic variability. Meiotic recombination does not always occur evenly across the chromosome, and therefore genetic and physical distances are not consistently in proportion. We discovered a 278 kb interval on the long arm of chromosome 10 (10 L) through analyzed 13,933 descendants of backcross population. The recombinant events distributed unevenly in the interval. The ratio of genetic to physical distance in the interval fluctuated about 47-fold. With the assistance of molecular markers, the interval was divided into several subintervals for further characterization. In agreement with previous observations, high gene-density regions such as subinterval A and B were also genetic recombination hot subintervals, and repetitive sequence-riched region such as subinterval C was also found to be recombination inert at the detection level of the study. However, we found an unusual subinterval D, in which the 72-kb region contained 6 genes. The gene-density of subinterval D was 5.8 times that of the genome-wide average. The ratio of genetic to physical distance in subinterval D was 0.58 cM/Mb, only about 3/4 of the genome average. We carried out an analysis of sequence polymorphisms and methylation status in subinterval D, and the potential causes of recombination suppression were discussed. This study was another case of a detailed genetic analysis of an unusual recombination region in the maize genome. PMID- 22057629 TI - The missing link: do cortical microtubules define plasma membrane nanodomains that modulate cellulose biosynthesis? AB - Cellulose production is a crucial aspect of plant growth and development. It is functionally linked to cortical microtubules, which self-organize into highly ordered arrays often situated in close proximity to plasma membrane-bound cellulose synthase complexes (CSCs). Although most models put forward to explain the microtubule-cellulose relationship have considered mechanisms by which cortical microtubule arrays influence the orientation of cellulose microfibrils, little attention has been paid to how microtubules affect the physicochemical properties of cellulose. A recent study using the model system Arabidopsis, however, indicates that microtubules can modulate the crystalline and amorphous content of cellulose microfibrils. Microtubules are required during rapid growth for reducing crystalline content, which is predicted to increase the degree to which cellulose is tethered by hemicellulosic polysaccharides. Such tethering is, in turn, critical for maintaining unidirectional cell expansion. In this article, we hypothesize that cortical microtubules influence the crystalline content of cellulose either by controlling plasma membrane fluidity or by modulating the deposition of noncellulosic wall components in the vicinity of the CSCs. We discuss the current limitations of imaging technology to address these hypotheses and identify the image acquisition and processing strategies that will integrate live imaging with super resolution three-dimensional information. PMID- 22057630 TI - The structure and functioning of the couplon in the mammalian cardiomyocyte. AB - The couplons of the cardiomyocyte form nanospaces within the cell that place the L-type calcium channel (Ca(v)1.2), situated on the plasmalemma, in opposition to the type 2 ryanodine receptor (RyR2), situated on the sarcoplasmic reticulum. These two molecules, which form the basis of excitation-contraction coupling, are separated by a very limited space, which allows a few Ca(2+) ions passing through Ca(v)1.2 to activate the RyR2 at concentration levels that would be deleterious to the whole cell. The limited space also allows Ca(2+) inactivation of Ca(v)1.2. We have found that not all couplons are the same and that their properties are likely determined by their molecular partners which, in turn, determine their excitability. In particular, there are a class of couplons that lie outside the RyR2-Ca(v)1.2 dyad; in this case, the RyR2 is close to caveolin-3 rather than Ca(v)1.2. These extra-dyadic couplons are probably controlled by the multitude of molecules associated with caveolin-3 and may modulate contractile force under situations such as stress. It has long been assumed that like the skeletal muscle, the RyR2 in the couplon are arranged in a structured array with the RyR2 interacting with each other via domain 6 of the RyR2 molecule. This arrangement was thought to provide local control of RyR2 excitability. Using 3D electron tomography of the couplon, we show that the RyR2 in the couplon do not form an ordered pattern, but are scattered throughout it. Relatively few are in a checkerboard pattern--many RyR2 sit edge-to-edge, a configuration which might preclude their controlling each other's excitability. The discovery of this structure makes many models of cardiac couplon function moot and is a current avenue of further research. PMID- 22057631 TI - Lyn deficiency affects B-cell maturation as well as survival. AB - Lyn, an Src-family protein tyrosine kinase expressed in B lymphocytes, contributes to initiation of BCR signaling and is also responsible for feedback inhibition of BCR signaling. Lyn-deficient mice have a decreased number of follicular B cells and also spontaneously develop a lupus-like autoimmunity. We used flow cytometric analysis, BrdU labeling and our mathematical models of B cell population dynamics, to analyze how Lyn deficiency impacts B-cell maturation and survival. We found that Lyn-deficient transitional 1 (T1) cells develop normally, but T2 cells develop primarily from the T1 subset in the spleen and fail to also develop directly from BM immature B cells. Lyn-deficient T2 cells either mature to the follicular B-cell type at a close to normal rate, or die in this compartment rather than access the T3 anergic subset. The ~ 40% of WT follicular cells that were short-lived exited primarily by joining the T3 anergic subset, whereas the ~ 15% Lyn(-/-) follicular cells that were not long lived had a high death rate and died in this compartment rather than entering the T3 subset. We hypothesize that exaggerated BCR signaling resulting from weak interactions with self-antigens is largely responsible for these alterations in Lyn-deficient B cells. PMID- 22057632 TI - How do MYBPC3 mutations cause hypertrophic cardiomyopathy? AB - It is well established that MYBPC3 mutations are the most common cause of hypertrophic cardiomyopathy, accounting for about half of identified mutations. However, when compared with mutations in other myofibrillar proteins that cause hypertrophic cardiomyopathy, MYBPC3 mutations seem to be the odd one out. The most striking characteristic of HCM mutations in MYBPC3 is that many are within introns and are predicted to cause aberrant splicing leading to a frameshift and a premature chain termination, yet the truncated peptides have never been identified in human heart tissue carrying these mutations. Instead of expression of a poison peptide we consistently observe haploinsufficiency of MyBP-C in MYBPC3 mutant human heart muscle. In this review we investigate the mechanism for MyBP-C haploinsufficiency and consider how this haploinsufficiency could cause hypertrophic cardiomyopathy. PMID- 22057633 TI - Divergent biophysical properties, gating mechanisms, and possible functions of the two skeletal muscle Ca(V)1.1 calcium channel splice variants. AB - Voltage-gated calcium channels are multi-subunit protein complexes that specifically allow calcium ions to enter the cell in response to membrane depolarization. But, for many years it seemed that the skeletal muscle calcium channel Ca(V)1.1 is the exception. The classical splice variant Ca(V)1.1a activates slowly, has a very small current amplitude and poor voltage sensitivity. In fact adult muscle fibers work perfectly well even in the absence of calcium influx. Recently a new splice variant of the skeletal muscle calcium channel Ca(V)1.1e has been characterized. The lack of the 19 amino acid exon 29 in this splice variant results in a rapidly activating calcium channel with high current amplitude and good voltage sensitivity. Ca(V)1.1e is the dominant channel in embryonic muscle, where the expression of this high calcium-conducting Ca(V)1.1 isoform readily explains developmental processes depending on L-type calcium currents. Moreover, the availability of these two structurally similar but functionally distinct channel variants facilitates the analysis of the molecular mechanisms underlying the unique current properties of the classical Ca(V)1.1a channel. PMID- 22057634 TI - Ahnak1 abnormally localizes in muscular dystrophies and contributes to muscle vesicle release. AB - Ahnak1 is a giant, ubiquitously expressed, plasma membrane support protein whose function in skeletal muscle is largely unknown. Therefore, we investigated whether ahnak would be influenced by alterations of the sarcolemma exemplified by dysferlin mutations known to render the sarcolemma vulnerable or by mutations in calpain3, a protease known to cleave ahnak. Human muscle biopsy specimens obtained from patients with limb girdle muscular dystrophy (LGMD) caused by mutations in dysferlin (LGMD2B) and calpain3 (LGMD2A) were investigated for ahnak expression and localization. We found that ahnak1 has lost its sarcolemmal localization in LGMD2B but not in LGMD2A. Instead ahnak1 appeared in muscle connective tissue surrounding the extracellular site of the muscle fiber in both muscular dystrophies. The entire giant ahnak1 molecule was present outside the muscle fiber and did only partially colocalize with CD45-positive immune cell infiltration and the extracelluar matrix proteins fibronectin and collagenVI. Further, vesicles shedded in response to Ca(2+) by primary human myotubes were purified and their protein content was analysed. Ahnak1 was prominently present in these vesicles. Electron microscopy revealed a homogenous population of vesicles with a diameter of about 150 nm. This is the first study demonstrating vesicle release from human myotubes that may be one mechanism underlying abnormally localized ahnak1. Taken together, our results define ahnak1 in muscle connective tissue as a novel feature of two genetically distinct muscular dystrophies that might contribute to disease pathology. PMID- 22057635 TI - Prospective monitoring of Epstein-Barr virus and other herpesviruses in patients with juvenile idiopathic arthritis treated with methotrexate and tocilizumab. AB - Methotrexate (MTX) is widely used for the treatment of articular-type juvenile idiopathic arthritis (JIA), but patients receiving MTX for rheumatoid arthritis have been reported to be at increased risk of reactivation of Epstein-Barr virus (EBV) and the development of lymphoproliferative disorder. The association between MTX and reactivation of herpesviruses in pediatric patients is not yet understood. We prospectively monitored the viral load of EBV, cytomegalovirus (CMV), and herpesvirus 6 (HHV-6) in four JIA patients treated with MTX for 12-24 months. Tocilizumab, an anti-interleukin 6 receptor monoclonal antibody, was added to the therapeutic regimen in three patients during the observation period. Prior to the administration of MTX, EBV and HHV-6 were detected by PCR in two patients. Significant increases in EBV and HHV-6 load were not observed following the administration of MTX or tocilizumab. In one patient, a relatively high EBV load remained detectable during 21 months of observation in the absence of clinical symptoms. CMV was not detected throughout the observation period in any patient. This is the first report monitoring the longitudinal DNA loads of EBV and other herpesviruses in JIA patients. EBV and HHV-6 were often detectable, but treatment with MTX and tocilizumab did not appear to influence the viral load. PMID- 22057636 TI - Outcome of pregnancy in type 1 diabetes mellitus (T1DMP): results from combined diabetes-obstetrical clinics in Dublin in three university teaching hospitals (1995-2006). AB - OBJECTIVE: To compare the pregnancy outcomes in all T1DMP attending at combined (diabetes-obstetric) outpatients clinics in three university teaching hospitals in Dublin from 1995 to 2006 with a non-diabetic control population (C) attending at antenatal outpatient clinics at the same hospitals over the same period. METHODS: T1DMP (n = 600) were compared with control non-diabetic pregnancies (n = 142,498). RESULTS: The spontaneous abortion rate was 15% in T1DMP versus 8% in C (p < 0.0001). Perinatal mortality rate was 3.3% in T1DMP compared to 0.9% in C (p < 0.001). The incidence of foetal macrosomia was 29% in T1DMP versus 16% in C (p < 0.001). CONCLUSIONS: Pregnancy outcomes in T1DMP remain worse than in the general population despite management of T1DMP in combined obstetric/diabetes clinics in a single centre using similar management protocols. These outcomes in our study population of T1DMP in Dublin appear better than some previously reported studies. PMID- 22057637 TI - Clozapine-induced leukopenia: arguments for rechallenge. PMID- 22057638 TI - Stromal caveolin-1 expression in breast carcinoma. Correlation with early tumor recurrence and clinical outcome. AB - Caveolin- (cav-1) has been linked to tumor progression and clinical outcome in breast cancer, but its role as a prognostic marker is still unclear. We evaluated stromal and tumor caveolin-1 expression in 91 breast carcinomas, and assessed the association between their expression and clinicopathologic variables as well as patient outcome and early tumor recurrence. Absence of stromal caveolin-1 expression was detected in 18.7% of cases, while 25.3% of cases revealed tumor epithelial caveolin-1 expression. Combined stromal and tumor caveolin-1 immunopositivity was seen in 24.2% of cases. Absence of stromal cav-1 associated with larger tumor size, higher grade, higher nodal stage, higher number of positive nodes, higher TNM stage, positive HER2 status, higher recurrence rate, and shorter mean progression free survival (PFS). Stromal cav-1 status was a significant predictor of PFS in ER+, PR +, and HER2 + tumors. In tamoxifen treated patients, absence of stromal Cav-1 was a significant predictor of poor clinical outcome, suggestive of tamoxifen resistance. Conversely, tumor epithelial and combined caveolin-1 expression, didnot associate with patient outcome. In multivariate analysis, only TNM stage independently associated with survival. Loss of stromal caveolin-1 is a novel breast cancer biomarker that can predict early tumor recurrence, short PFS, and tamoxifen- resistance. Thus, its use as a predictive biomarker, especially in lower grade, lower stage, ER+, PR+, HER2+, and tamoxifen treated patients may allow for early interventions with more aggressive therapies. Thus, stromal marker expression and epithelial-stromal cross talk may be critical for tumor progression and metastasis. PMID- 22057639 TI - Effect of intramammary infusion of rbGM-CSF on SCC and expression of polymorphonuclear neutrophil adhesion molecules in subclinical mastitis cows. AB - The effect of rbGM-CSF intramammary infusion on the subclinical mastitis was evaluated by the somatic cell count (SCC) and expression of adhesion molecules (CD62L and CD11b) on the surface of neutrophils (PMN) in blood and milk. Fifteen cows diagnosed to have subclinical mastitis were used in this study. Seven cows showed a decrease in the SCC (decreased group), whereas 8 cows showed an increase in the SCC (increased group) 7 days after infusion of rbGM-CSF compared to pre infusion level. The percentage of CD62+ cells tended to be lower and CD11b+cells tended to be higher at 6 h on blood PMN in the decreased group of cows. Increased group of cows showed opposite tendencies. The mean fluorescent intensity of these adhesion molecules expressed on PMN in blood and milk was similar in both groups. These results suggested some association between expression of adhesion molecules and changes in SCC by rbGM-CSF. Responsiveness of PMN adhesion molecules to rbGM CSF might determine the changes in SCC of the subclinical mastitic cows after infusion of rbGM-CSF. PMID- 22057640 TI - Ultrasmall rigid particles as multimodal probes for medical applications. PMID- 22057641 TI - Interfacial self-assembly of amino acids and peptides: scanning tunneling microscopy investigation. AB - Proteins play important roles in human daily life. To take advantage of the lessons learned from nature, it is essential to investigate the self-assembly of subunits of proteins, i.e., amino acids and polypeptides. Due to its high resolution and versatility of working environment, scanning tunneling microscopy (STM) has become a powerful tool for studying interfacial molecular assembly structures. This review is intended to reflect the progress in studying interfacial self-assembly of amino acids and peptides by STM. In particular, we focus on environment-induced polymorphism, chiral recognition, and coadsorption behavior with molecular templates. These studies would be highly beneficial to research endeavors exploring the mechanism and nanoscale-controlling molecular assemblies of amino acids and polypeptides on surfaces, understanding the origin of life, unravelling the essence of disease at the molecular level and deeming what is necessary for the "bottom-up" nanofabrication of molecular devices and biosensors being constructed with useful properties and desired performance. PMID- 22057642 TI - A message to the millennial generation: suggestions for a successful transition into medicine as a profession. PMID- 22057643 TI - Use of seniors as mentors to medical students: a collaboration between the University of South Carolina School of Medicine and the Medical University of South Carolina. PMID- 22057644 TI - The "next medicine"? PMID- 22057645 TI - The state of pediatric traumatic brain injury in SC. PMID- 22057646 TI - Does health plan type contribute to difference in diabetes care? PMID- 22057647 TI - Practical roadmap and limits to nanostructured photovoltaics. AB - The significant research interest in the engineering of photovoltaic (PV) structures at the nanoscale is directed toward enabling reductions in PV module fabrication and installation costs as well as improving cell power conversion efficiency (PCE). With the emergence of a multitude of nanostructured photovoltaic (nano-PV) device architectures, the question has arisen of where both the practical and the fundamental limits of performance reside in these new systems. Here, the former is addressed a posteriori. The specific challenges associated with improving the electrical power conversion efficiency of various nano-PV technologies are discussed and several approaches to reduce their thermal losses beyond the single bandgap limit are reviewed. Critical considerations related to the module lifetime and cost that are unique to nano-PV architectures are also addressed. The analysis suggests that a practical single-junction laboratory power conversion efficiency limit of 17% and a two-cell tandem power conversion efficiency limit of 24% are possible for nano-PVs, which, when combined with operating lifetimes of 10 to 15 years, could position them as a transformational technology for solar energy markets. PMID- 22057648 TI - Prison medicine, public health policy and ethics: the Geneva experience. AB - The health care of prisoners represents a public health priority. However, in many countries, the pursuit of public health goals in prison is not granted. Introducing condom distribution and syringe exchange in prisons remains the exception. This article describes the example of a Swiss canton in which the legal framework enables health-care personnel to put into practice health care that is equivalent to the care available to non imprisoned persons including harm reduction measures for prisoners. The article describes the medical institutions in charge of health care for prisoners and the legal and ethical framework, its repercussions on the clinical and public health context, as well as persisting difficulties. The Geneva experience shows that in spite of the legal context, preventive measures, free informed consent and confidentiality have to be constantly defended by physicians and public health authorities. Both need to be regularly educated on their obligations towards prisoner patients. A complaint mechanism granted to detainees as part of the legal framework is important to adapt existing practice to new challenges. PMID- 22057649 TI - [Homo erectus haemophilus - the haemophilic arthropathy of the leg]. AB - The haemophilic arthropathy of the hip, the knee and the ankle makes a painful loss of the degree of movement. Especially the muscles which bend these joints are contracted. This means a loss of posture and quality of life as well. This article demonstrates the possibilities of the conservative and operative treatment and represents an algorithm of the indication of operative measurements. Finally, there is a report about the straighten up and the re socialisation of a patient with haemophilia by total hip and knee arthroplasty. PMID- 22057650 TI - Conjugated polymers containing a 2,2'-biimidazole moiety--a novel fluorescent sensing platform. AB - Two novel conjugated polymers containing a 2,2'-biimidazole moiety have been designed, synthesized, and demonstrated to be used as an effective fluorescent sensing platform for detection of Ag(+) and cysteine. This is the first example utilizing a fluorescent conjugated polymer-Ag(+) complex to selectively detect Cys with a nanomolar range detection limit. PMID- 22057651 TI - Action mirroring and action understanding: an ideomotor and attentional account. AB - Research over the last years has provided compelling evidence that the perception of an action leads to an activation of the perceiver's own motor system. Furthermore, it has been suggested that such a mirroring process supports the understanding of the other's action. However, the precise neurocognitive mechanisms behind this process remained unclear. Moreover, the hypothesis that activation in the motor system is directly related to the ascription of an intention to another person has been repeatedly criticized on conceptual grounds. This article suggests a conceptual framework that deals with both issues. Applying the ideomotor theory to the realm of action perception, it is suggested that the activation of one's own motor system through the perception of another person's action leads to an activation of the associated representation of the action's typical effect. This activation, in turn, modulates (visual) attention and leads to a facilitated processing of potentially relevant information in the environment and may so contribute to action understanding. PMID- 22057652 TI - Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study. AB - BACKGROUND: Diuretic treatment for heart failure may lead to an increased urinary thiamine excretion and in long-term thiamine deficiency, which may further compromise cardiac function. This study evaluated the effect of high dose thiamine supplementation in heart failure patients. METHODS: Nine patients with diuretic treatment for symptomatic chronic heart failure and a left ventricular ejection fraction (LVEF) <40% were randomly assigned to receive thiamine (300 mg/day) or placebo for 28 days. After a wash-out of 6 weeks, the patients crossed over to a second treatment period. The primary outcome was a change in LVEF. RESULTS: Mean age was 56.7 +/- 9.2 years (range 44.9-75.4 years). Baseline LVEF was similar for both treatment groups (29.5% in the thiamine group and 29.5% in the placebo group, P = 0.911). After 28 days of thiamine treatment, the LVEF increased to 32.8% which was significantly (P = 0.024) different from the LVEF in the placebo group (28.8%). This corresponds to a treatment effect for LVEF of 3.9% in absolute terms. CONCLUSIONS: This study suggests that thiamine supplementation has beneficial effects on cardiac function in patients with diuretic drugs for symptomatic chronic heart failure. Subclinical thiamine deficiency is probably an underestimated issue in these outpatients. PMID- 22057653 TI - Evaluation of defibrillation safety margin in modern implantable cardioverter defibrillators after administration of amiodarone. AB - AIM: The adjunctive medication with amiodarone plays a major role in patients with an implantable cardioverter defibrillator (ICD). Amiodarone as class III antiarrhythmic drug may significantly alter the defibrillation threshold (DFT). Conflicting results exist on the clinical relevance of a DFT rise on amiodarone. The only prospective study on this issue included only a small number of patients on amiodarone. The purpose of this study was to assess the safety and clinical relevance of repeat defibrillator testing after initiation of amiodarone in modern defibrillator systems. METHODS AND RESULTS: We assessed risks and clinical consequences of retesting defibrillation safety margin after initiation of amiodarone in 130 consecutive patients. All patients underwent intraoperative testing at the time of first ICD implantation. A repeated VF induction and defibrillator test (by protocol with a single shock and 10 J safety margin) after a total dose of at least 10 g amiodarone 4-6 weeks after initiation of medication was performed. DFT testing after initiation of amiodarone was safe as there were no complications that led to a prolonged hospital stay. In 4 of 114 patients with a left-sided device (1.6%) and 3 of 7 patients with a right-sided device (42.8%), a 10 J safety margin could not be achieved. As a result 4 patients (3.1% of study collective) had a revision of the system. CONCLUSION: Repeat defibrillation testing after administration of amiodarone therapy rarely fails in patients with left-sided devices. We observed a higher test failure in patients with a device in the right-subpectoral position although this subgroup was small. Repeat defibrillator testing is safe as no relevant complications were observed. PMID- 22057654 TI - Immunization induces activation of bone marrow eosinophils required for plasma cell survival. AB - Eosinophils not only have multiple functions as effector cells of the innate immune system but also as modulators of immune responses. As producers of cytokines required for plasma cell survival, they are essential for the long-term maintenance of plasma cells in the BM. Here we show that the activation of eosinophils both in vitro and in vivo enhances the expression of the plasma cell survival factors APRIL, IL-6, IL-4, IL-10 and TNF-alpha. The in vivo activation of eosinophils was independent of the type of adjuvant used for primary immunization. Although eosinophils were activated by adjuvant itself, a stable activation and a constant increase in BM eosinophils were observed only in the presence of antigen. Thus, the numbers and the quality of eosinophils were dependent on priming the adaptive immune system. With secondary immunization and re-activation of antigen-dependent memory cells, the ability of eosinophils to promote plasma cell survival was further increased. These findings suggest that in T-cell-dependent immune responses eosinophils are conditioned to support the long-term survival of plasma cells in the BM, and furthermore imply that through accelerated numbers of eosinophils, stable plasma cell survival niches are established and the long-term survival of plasma cells is ensured. PMID- 22057655 TI - Intracranial transplantation of monocyte-derived multipotential cells enhances recovery after ischemic stroke in rats. AB - Cell transplantation has emerged as a potential therapy to reduce the neurological deficits caused by ischemic stroke. We previously reported a primitive cell population, monocyte-derived multipotential cells (MOMCs), which can differentiate into mesenchymal, neuronal, and endothelial lineages. In this study, MOMCs and macrophages were prepared from rat peripheral blood and transplanted intracranially into the ischemic core of syngeneic rats that had undergone a left middle cerebral artery occlusion procedure. Neurological deficits, as evaluated by the corner test, were less severe in the MOMC transplanted rats than in macrophage-transplanted or mock-treated rats. Histological evaluations revealed that the number of microvessels that had formed in the ischemic boundary area by 4 weeks after transplantation was significantly greater in the MOMC-transplanted rats than in the control groups. The blood vessel formation was preceded by the appearance of round CD31(+) cells, which we confirmed were derived from the transplanted MOMCs. Small numbers of bloodvessels incorporating MOMC-derived endothelial cells expressing a mature endothelial marker RECA-1 were detected at 4 weeks after transplantation. In addition, MOMCs expressed a series of angiogenic factors, including vascular endothelial growth factor, angiopoetin-1, and placenta growth factor (PlGF). These findings provide evidence that the intracranial delivery of MOMCs enhances functional recovery by promoting neovascularization in a rat model for ischemic stroke. PMID- 22057656 TI - Relationship between birth spacing, child maltreatment, and child behavior and development outcomes among at-risk families. AB - Prior research indicates that closely spaced births are associated with poor outcomes for the mother and subsequent child. Limited research has focused on outcomes for the index child (the child born immediately prior to a subsequent child in a birth interval). The objectives are to assess the association of short birth intervals in at-risk families with: (1) indicators of harsh and neglectful parenting behaviors towards the index child, including substantiated maltreatment reports across 6 years; and (2) the index child's behavior and development in first grade. This is a longitudinal study of 658 women screened to be at-risk for child maltreatment. Twenty percent of women had a rapid repeat birth (RRB), defined as the birth of a subsequent child within 24 months of the index child. Generalized estimating equations, survival analyses, and linear and logistic regression models were used to assess the associations between RRB and index child outcomes. Women with an RRB were more likely than those without an RRB to report neglectful parenting of the index child. Children of mothers with an RRB were more likely than children of mothers without an RRB to have more behavioral problems and lower cognitive functioning in first grade. This study is among the first to focus on the associations of birth spacing with maltreatment, behavior and development outcomes in the index child. Future work regarding the effects of birth spacing should include a focus on the index child. PMID- 22057657 TI - Attitudes toward birth spacing among low-income, postpartum women: a qualitative analysis. AB - To explore attitudes about birth spacing among low-income, recently postpartum women, using qualitative methods, seven focus groups among postpartum women were conducted, probing knowledge and attitudes related to desired birth spacing. Transcripts of the discussions were reviewed and coded for salient themes using a Grounded Theory approach. In regards to whether to pursue pregnancy in the future, major themes included the availability of adequate resources, current family composition and the role of partners. With respect to when to have a next pregnancy, themes centered around the desire for particular intervals between siblings. Discussions of the effect of spacing on the health of the mother or child did not emerge frequently. Themes underlying postpartum women's desire for particular birth spacing are varied, but social and family considerations seem to predominate over concerns or knowledge about potential health effects. Improving women's knowledge about these consequences could lead to lowering the incidence of short interpregnancy intervals, known to be associated with adverse perinatal outcomes. PMID- 22057658 TI - Profiling of serum antibodies with printed glycan array: room for data misinterpretation. AB - Using an example of Galbeta1-3GlcNAc (Le(C)) related glycans, we here demonstrate a risk of data misinterpretation when polyclonal antibodies are probed for their glycan-binding specificities with help of a printed glycan array (PGA). Affinity isolation of antibodies from human serum using Le(C)-Sepharose or 3'-O-SuLe(C) Sepharose in conditions of excess of the adsorbents generated identical material regardless of the affinity ligand, with the antibodies equally capable of binding to Le(C) and to 3'-O-SuLe(C) disaccharides, as well as to 3'-O-SiaLe(C) trisaccharide. More detailed profiling has shown that the isolated antibodies bind to the inner part of Galbeta1-3GlcNAc disaccharide. We therefore conclude that serum does not contain different subsets of antibodies specific either to Le(C) or to 3'-O-SuLe(C), despite their visibly different binding signals to these glycans on PGA. PMID- 22057659 TI - Identification and characterization of the short variable region of the Japanese encephalitis virus 3' NTR. AB - Since the 1980s, the Japanese encephalitis virus (JEV) variants with slightly short variable regions (VR) of the 3' non-translated region (NTR) have been found; however, the implications of these short VR remain unclear. We recently identified two novel types of short VR (5 and 9 nt shorter than that of major group of genotype I JEV strains) of genotype I JEV isolates. To elucidate the impact of these short VR on the replication and virulence of JEV, we generated five recombinant JEV viruses: M41-d5 and M41-d9 have deletions in the VR that correspond to those observed in some recent JEV isolates, M41-d5d9 has both the 5 and 9-nt deletions in the VR, M41-d27 has a large deletion that encompasses both the 5- and 9-nt deletion regions, and M41-a13 has a 13-nt sequence insertion of the genotype III JEV strain Beijing-1 into the parent genotype I JEV strain Mie/41/2002 genome. The recombinant viruses and the parent virus, except for the M41-d27 mutant, showed similar growth properties in mammalian and mosquito cell lines. Mouse challenge experiments indicated that no significant differences among the recombinant viruses M41-d5d9, M41-d27, M41-a13, and the parent virus. Our results suggest that the short VR in JEV 3' NTR do not affect its growth in vitro or its pathogenicity in mice. PMID- 22057660 TI - Antibiotic prophylaxis for transrectal ultrasound biopsy of the prostate in Ireland. AB - INTRODUCTION: Prostate cancer is the most common solid cancer affecting men in Ireland. Transrectal ultrasound (TRUS) biopsies of the prostate are routinely performed to diagnose prostate cancer. They are, in general, a safe procedure but are associated with a significant risk of infective complications ranging from fever, urinary tract infection to severe urosepsis. At present, there are no recommended national guidelines on the use of antibiotic prophylaxis to minimise the risk of infective complications post-TRUS biopsy. AIM: To review the antibiotic prophylaxis for TRUS biopsy used in Irish hospitals. METHOD: We used a standard telephone questionnaire to establish what antibiotic protocol is in use in each hospital. RESULTS: 40 hospitals were contacted, of which 29 perform TRUS biopsies. In the majority of hospitals, TRUS biopsies are carried out in the radiology department. All hospitals administer antibiotic prophylaxis but there is wide variation in the protocols used. There are five different antibiotics prescribed, ciprofloxacin being the most common. Treatment protocols vary from 1 to 10 days antibiotic cover post procedure. CONCLUSION: There is a lack of standardisation of antibiotic prophylaxis in Irish hospitals. There is a need for guidelines to clarify the most appropriate antibiotic, route of administration and duration of treatment. PMID- 22057663 TI - The effect of methylphenidate and rearing environment on behavioral inhibition in adult male rats. AB - RATIONALE: The ability to withhold reinforced responses-behavioral inhibition-is impaired in various psychiatric conditions including Attention Deficit Hyperactivity Disorder (ADHD). Methodological and analytical limitations have constrained our understanding of the effects of pharmacological and environmental factors on behavioral inhibition. OBJECTIVES: To determine the effects of acute methylphenidate (MPH) administration and rearing conditions (isolated vs. pair housed) on behavioral inhibition in adult rats. METHODS: Inhibitory capacity was evaluated using two response-withholding tasks, differential reinforcement of low rates (DRL) and fixed minimum interval (FMI) schedules of reinforcement. Both tasks made sugar pellets contingent on intervals longer than 6 s between consecutive responses. Inferences on inhibitory and timing capacities were drawn from the distribution of withholding times (interresponse times, or IRTs). RESULTS: MPH increased the number of intervals produced in both tasks. Estimates of behavioral inhibition increased with MPH dose in FMI and with social isolation in DRL. Nonetheless, burst responding in DRL and the divergence of DRL data relative to past studies, among other limitations, undermined the reliability of DRL data as the basis for inferences on behavioral inhibition. CONCLUSIONS: Inhibitory capacity was more precisely estimated from FMI than from DRL performance. Based on FMI data, MPH, but not a socially enriched environment, appears to improve inhibitory capacity. The highest dose of MPH tested, 8 mg/kg, did not reduce inhibitory capacity but reduced the responsiveness to waiting contingencies. These results support the use of the FMI schedule, complemented with appropriate analytic techniques, for the assessment of behavioral inhibition in animal models. PMID- 22057662 TI - Similarities and differences between pathological gambling and substance use disorders: a focus on impulsivity and compulsivity. AB - RATIONALE: Pathological gambling (PG) has recently been considered as a "behavioral" or nonsubstance addiction. A comparison of the characteristics of PG and substance use disorders (SUDs) has clinical ramifications and could help advance future research on these conditions. Specific relationships with impulsivity and compulsivity may be central to understanding PG and SUDs. OBJECTIVES: This review was conducted to compare and contrast research findings in PG and SUDs pertaining to neurocognitive tasks, brain function, and neurochemistry, with a focus on impulsivity and compulsivity. RESULTS: Multiple similarities were found between PG and SUDs, including poor performance on neurocognitive tasks, specifically with respect to impulsive choice and response tendencies and compulsive features (e.g., response perseveration and action with diminished relationship to goals or reward). Findings suggest dysfunction involving similar brain regions, including the ventromedial prefrontal cortex and striatum and similar neurotransmitter systems, including dopaminergic and serotonergic. Unique features exist which may in part reflect influences of acute or chronic exposures to specific substances. CONCLUSIONS: Both similarities and differences exist between PG and SUDs. Understanding these similarities more precisely may facilitate treatment development across addictions, whereas understanding differences may provide insight into treatment development for specific disorders. Individual differences in features of impulsivity and compulsivity may represent important endophenotypic targets for prevention and treatment strategies. PMID- 22057664 TI - Distinct regulation of stearoyl-CoA desaturase 1 gene expression by cis and trans C18:1 fatty acids in human aortic smooth muscle cells. AB - Consumption of trans fatty acids is positively correlated with cardiovascular diseases and with atherogenic risk factors. Trans fatty acids might play their atherogenic effects through lipid metabolism alteration of vascular cells. Accumulation of lipids in vascular smooth muscle cells is a feature of atherosclerosis and a consequence of lipid metabolism alteration. Stearoyl-CoA desaturase 1 (scd1) catalyses the production of monounsaturated fatty acids (e.g. oleic acid) and its expression is associated with lipogenesis induction and with atherosclerosis development. We were interested in analysing the regulation of delta-9 desaturation rate and scd1 expression in human aortic smooth muscle cells (HASMC) exposed to cis and trans C18:1 fatty acid isomers (cis-9 oleic acid, trans-11 vaccenic acid or trans-9 elaidic acid) for 48 h at 100 MUM. Treatment of HASMC with these C18:1 fatty acid isomers led to differential effects on delta-9 desaturation; oleic acid repressed the desaturation rate more potently than trans 11 vaccenic acid, whereas trans-9 elaidic acid increased the delta-9 desaturation rate. We then correlated the delta-9 desaturation rate with the expression of scd1 protein and mRNA. We showed that C18:1 fatty acids controlled the expression of scd1 at the transcriptional level in HASMC, leading to an increase in scd1 mRNA content by trans-9 elaidic acid treatment, whereas a decrease in scd1 mRNA content was observed with cis-9 oleic acid and trans-11 vaccenic acid treatments. Altogether, this work highlights a differential capability of C18:1 fatty acid isomers to control scd1 gene expression, which presumes of different consequent effects on cell functions. PMID- 22057665 TI - The impact of using different tariffs to value EQ-5D health state descriptions: an example from a study of acute cough/lower respiratory tract infections in seven countries. AB - When using the EQ-5D in European cross-national studies, there is no consensus over whether the European value set (EVS), country specific value sets (CVS) or UK value set (UKVS) should be used. Data on health outcomes were collected in 7 countries. EQ-5D index scores were generated for each country using all three value sets. QALYs gained over 4 weeks based on EQ-5D scores were also generated in order to investigate the implications for cost-utility analysis. EQ-5D scores obtained using the EVS were similar to values obtained using the CVS and UKVS in all countries. CVS-based EQ-5D scores were on average associated with a smaller baseline-to-week 4 change/improvement in all countries (except in Wales and Belgium) while UKVS-based EQ-5D scores showed the largest improvement over the same period for every country. With regards to cost-utility analysis, the results suggest that in most countries (with the exception of Belgium and Finland), using different tariffs to value EQ-5D would not have made a difference to the decisions based on the results of cost-utility analysis. PMID- 22057666 TI - An analysis of the influence of framework aspects on the study design of health economic modeling evaluations. AB - Research and practical guidelines have many implications for how to structure a health economic study. A major focus in recent decades has been the quality of health economic research. In practice, the factors influencing a study design are not limited to the quest for quality. Moreover, the framework of the study is important. This research addresses three major questions related to these framework aspects. First, we want to know whether the design of health economic studies has changed over time. Second, we want to know how the subject of a study, whether it is a process or product innovation, influences the parameters of the study design. Third, one of the most important questions we will answer is whether and how the study's source of funding has an impact on the design of the research. To answer these questions, a total of 234 health economic studies were analyzed using a correspondence analysis and a logistic regression analysis. All three categories of framework factors have an influence on the aspects of the study design. Health economic studies have evolved over time, leading to the use of more advanced methods like complex sensitivity analyses. Additionally, the patient's point of view has increased in importance. The evaluation of product innovations has focused more on utility concepts. On the other hand, the source of funding may influence only a few aspects of the study design, such as the use of evaluation methods, the source of data, and the use of certain utility measures. The most important trends in health care, such as the emphasis on the patients' point of view, become increasingly established in health economic evaluations with the passage of time. Although methodological challenges remain, modern information and communication technologies provide a basis for increasing the complexity and quality of health economic studies if used frequently. PMID- 22057667 TI - Exploiting diverse stereochemistry of beta-amino acids: toward a rational design of sheet-forming beta-peptide systems. AB - Due to the two methylene groups in their backbone, beta-amino acids can adopt numerous secondary structures, including helices, sheets and nanotubes. Chirality introduced by the additional side chains can significantly influence the folding preference of beta-peptides composed of chiral beta-amino acids. However, only conceptual suggestions are present in the literature about the effect of chirality on folding preferences. Summarizing both the experimental and computational results, Seebach (Chem Biodivers 1:1111-1240, 2004) has proposed the first selection rule on the effect of side chain chirality, on the folding preference of beta-peptides. In order to extend and fine-tune the aforementioned predictions of Seebach, we have investigated its validity to the novel type of apolar sheet proposed recently (Pohl et al. in J Phys Chem B 114:9338-9348, 2010). In order to facilitate the rational design of sheet-like structures, a systematic study on the effect of chirality on "apolar" sheet stability is presented on disubstituted [HCO-beta-Ala-beta(2,3)-hAla-beta-Ala-NH(2)](2) model peptides calculated at the M05-2X/6-311++G(d,p)//M05-2X/6-31G(d) and B3LYP/6 311++G(d,p)//B3LYP/6-31G(d) levels of theory both in vacuum and in polar and apolar solvents. In addition, both types of "apolar" sheets were investigated; the one with two strands of identical (AA) and enantiomeric (AB) backbone structure. Our results show that heterochirally disubstituted sheets have the greatest preference for sheet formation (DeltaG ~ -11 kcal mol(-1)). However, in contrast to Seebach's predictions, "homochiral disubstitution" itself does not necessarily disrupt the sheet structure, rather it could result stable fold (DeltaG ~ -5 kcal mol(-1)). Results indicate that both the methyl group orientation and the local conformational effect of substitution affects sheet stability, as point chirality was found to have influence only on the backbone torsional angles. These results enabled us to extend and generalize Seebach's predictions and to propose a more general and accurate "rule of thumb" describing the effect of chirality on sheet stability. This offers an easy-to-use summary on how to design beta-peptide sheet structures. We conclude that heterochirally disubstituted models are the best candidates for sheet formation, if the two strands are substituted in a way to create identical torsional angle sets on the two backbones for ideal hydrogen-bonding pattern. With adequately selected side chains, homochirally disubtituted derivatives may also form sheet structures, and the position of methyl groups would prevent assembly of more than two strands making it ideal to create hairpins. PMID- 22057668 TI - Electronic bond-to-bond fluxes in pericyclic reactions: synchronous or asynchronous? AB - One at a time or all at once? Electronic fluxes during a pericyclic reaction in the electronic ground state--exemplified for the degenerate Cope rearrangement of semibullvalene--may proceed either synchronously or asynchronously. Quantum simulations show that the mechanism is determined by the preparation of the reactants, for example, synchronous at cryogenic temperatures (tunneling) but asynchronous when induced by selective laser pulses (with energy over the barrier). PMID- 22057669 TI - Indications to teriparatide treatment in patients with osteoporosis. AB - To prevent osteoporotic fracture occurrence, a variety of treatment regimens with different mechanisms of action is available. The antiresorptive bisphosphonate drugs are currently the most commonly prescribed agents in the management of patients with osteoporosis. The recombinant amino-terminal fragment of human parathyroid hormone (Teriparatide) is a bone anabolic agent which reduces fracture risk by increasing bone mass and improving bone microarchitecture. Teriparatide treatment reduces vertebral and non-vertebral fracture risk markedly in women and men with idiopathic osteoporosis, or with glucocorticoid-induced osteoporosis. Teriparatide should thus be considered as first line treatment for postmenopausal women and for men with severe osteoporosis. PMID- 22057670 TI - The integration of nasoalveolar molding in the treatment of cleft lip and palate: a comprehensive treatment of children born with cleft lip and palate. PMID- 22057671 TI - Behcet's disease with recurrent erythema multiforme in a 20 year-old African American male. PMID- 22057672 TI - Improving compliance: does it matter to your patients if you are spiritual? PMID- 22057673 TI - Eleanor W. Townsend, MD. PMID- 22057674 TI - Mending Medicaid. PMID- 22057675 TI - The ubiquitin-like protein, ISG15, is a novel tumor-associated antigen for cancer immunotherapy. AB - The recent announcement of the first FDA-approved therapeutic vaccine for prostate cancer, Sipuleucel-T, is a watershed moment for the field of tumor immunotherapy. However, while Sipuleucel-T provides a powerful tool to clinicians for the most prevalent form of cancer in men, there remains an unmet need for a similar therapeutic strategy against breast cancer, the most prevalent cancer in women. While current breast cancer vaccines in development target several antigens, the most prevalent is the tumor-associated antigen, HER2. Initial results with HER2 vaccines appear promising in terms of efficacy; however, the lack of HER2 overexpression by a majority of breast tumors and the safety concerns associated with current HER2-targeted immunotherapy suggest that additional therapeutic strategies would be beneficial. Recently, several studies have identified ISG15 as a molecule highly expressed in numerous malignancies. ISG15 is a small ubiquitin-like protein regulated by type-I interferon and classically associated with viral defense. Elevated ISG15 expression in breast cancer is especially well documented and is independent of HER2, progesterone receptor, and estrogen receptor status. Additionally, high ISG15 expression in breast cancer correlates with an unfavorable prognosis and poor responses to traditional treatment strategies such as chemotherapy and radiation. To overcome these challenges, we employ a novel strategy to specifically target tumor associated ISG15 expression with immunotherapy. We demonstrate that vaccination against ISG15 results in significant CD8-mediated reductions in both primary and metastatic mammary tumor burden. These results validate ISG15 as a tumor associated antigen for cancer immunotherapy. PMID- 22057676 TI - Scutellaria extract and wogonin inhibit tumor-mediated induction of T(reg) cells via inhibition of TGF-beta1 activity. AB - A number of studies have implicated tumor-induced T(reg) cell activity in the sub optimal response to therapeutic vaccines. Development of neo-adjuvant strategies targeting T(reg) cells is therefore imperative. Scutellaria extracts or constituent flavonoids have shown encouraging efficacy against various tumors, including gliomas, in both pre-clinical and clinical studies. We report here, for the first time, that Scutellaria ocmulgee leaf extract (SocL) and flavonoid wogonin could inhibit TGF-beta1-induced T(reg) activity in malignant gliomas. F344 rats, subcutaneously transplanted with F98 gliomas, were treated with SocL. There was a significant inhibition of intra-tumoral TGF-beta1 and T(reg) cell frequency as well as peripheral blood TGF-beta1 levels in SocL-treated animals compared to the controls. SocL extract and wogonin also inhibited glioma-induced, TGF-beta1-mediated T(reg) activity in vitro. SocL extract and wogonin also inhibited the secretion of IL-10 in T(reg) culture; whereas the level of IL-2 was either unchanged or marginally enhanced. We also observed an inhibition of Smad 3, GSK-3beta and ERK1/2 signaling by SocL and wogonin in T(reg) cells, while phosphorylation of P38 MAPK was considerably enhanced, indicating that SocL or wogonin could inhibit the T cells' response to TGF-beta1 via modulation of both Smad and non-Smad signaling pathways. Overall, this study suggests that Scutellaria can potentially reverse tumor-mediated immune suppression via inhibition of TGF-beta1 secretion as well as via inhibition of T cells' response to TGF-beta1. This may provide an opportunity for developing a novel adjuvant therapeutic strategy for malignant gliomas, combining Scutellaria with immunotherapy and chemo/radio-therapeutic regimen, which could potentially improve the disease outcome. PMID- 22057677 TI - Epitope-targeted cytotoxic T cells mediate lineage-specific antitumor efficacy induced by the cancer mucosa antigen GUCY2C. AB - Guanylyl cyclase C (GUCY2C) is the index cancer mucosa antigen, an emerging class of immunotherapeutic targets for the prevention of recurrent metastases originating in visceral epithelia. GUCY2C is an autoantigen principally expressed by intestinal epithelium, and universally by primary and metastatic colorectal tumors. Immunization with adenovirus expressing the structurally unique GUCY2C extracellular domain (GUCY2C(ECD); Ad5-GUCY2C) produces prophylactic and therapeutic protection against GUCY2C-expressing colon cancer metastases in mice, without collateral autoimmunity. GUCY2C antitumor efficacy is mediated by a unique immunological mechanism involving lineage-specific induction of antigen targeted CD8(+) T cells, without CD4(+) T cells or B cells. Here, the unusual lineage specificity of this response was explored by integrating high-throughput peptide screening and bioinformatics, revealing the role for GUCY2C-directed CD8(+) T cells targeting specific epitopes in antitumor efficacy. In BALB/c mice vaccinated with Ad5-GUCY2C, CD8(+) T cells recognize the dominant GUCY2C(254-262) epitope in the context of H-2K(d), driving critical effector functions including interferon gamma secretion, cytolysis ex vivo and in vivo, and antitumor efficacy. The ability of GUCY2C to induce lineage-specific responses targeted to cytotoxic CD8(+) T cells recognizing a single epitope mediating antitumor efficacy without autoimmunity highlights the immediate translational potential of cancer mucosa antigen-based vaccines for preventing metastases of mucosa-derived cancers. PMID- 22057679 TI - Virus-like particles induce robust human T-helper cell responses. AB - Among synthetic vaccines, virus-like particles (VLPs) are used for their ability to induce strong humoral responses. Very little is reported on VLP-based-vaccine induced CD4(+) T-cell responses, despite the requirement of helper T cells for antibody isotype switching. Further knowledge on helper T cells is also needed for optimization of CD8(+) T-cell vaccination. Here, we analysed human CD4(+) T cell responses to vaccination with MelQbG10, which is a Qbeta-VLP covalently linked to a long peptide derived from the melanoma self-antigen Melan-A. In all analysed patients, we found strong antibody responses of mainly IgG1 and IgG3 isotypes, and concomitant Th1-biased CD4(+) T-cell responses specific for Qbeta. Although less strong, comparable B- and CD4(+) T-cell responses were also found specific for the Melan-A cargo peptide. Further optimization is required to shift the response more towards the cargo peptide. Nevertheless, the data demonstrate the high potential of VLPs for inducing humoral and cellular immune responses by mounting powerful CD4(+) T-cell help. PMID- 22057678 TI - Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen. AB - Twenty-seven subjects with squamous cell cancer of the head and neck received the neoadjuvant IRX-2 immunotherapy regimen prior to surgery in a Phase 2 trial. Pretreatment tumor biopsies were compared with the primary tumor surgical specimens for lymphocyte infiltration, necrosis and fibrosis, using hematoxylin and eosin stain and immunohistochemistry in 25 subjects. Sections were examined by three pathologists. Relative to pretreatment biopsies, increases in lymphocyte infiltration (LI) were seen using H and E or immunohistochemistry. CD3+ CD4+ T cells and CD20+ B cells were primarily found in the peritumoral stroma and CD3+ CD8+ T cells and CD68+ macrophages were mainly intratumoral. LI in the surgical specimens were associated with reductions in the primary tumor size. Improved survival at 5 years was correlated with high overall LI in the tumor specimens. Neoadjuvant IRX-2 immunotherapy regimen may restore immune responsiveness presumably by mobilizing tumor infiltrating effector lymphocytes and macrophages into the tumor. PMID- 22057680 TI - Nutrient and food intakes of middle-aged adults at low risk of cardiovascular disease: the international study of macro-/micronutrients and blood pressure (INTERMAP). AB - PURPOSE: Individuals with favorable levels of readily measured cardiovascular disease (CVD) risk factors (low risk, LR) experience low long-term rates of CVD mortality and greater longevity. The purpose of the current study was to compare nutrient/food intakes of LR participants with participants not LR in the INTERMAP study. METHODS: Men and women (40-59 years) from 17 population samples in four countries (China, Japan, UK, US) provided four 24-h dietary recalls and two timed 24-h urine collections. LR was defined as meeting all of the following CVD risk criteria: systolic/diastolic blood pressure (BP) <= 120/ <= 80 mmHg; no drug treatment for high BP, hyperlipidemia, or CVD; non-smoking; BMI <25.0 kg/m(2) (US, UK) or <23.0 kg/m(2) (China, Japan); alcohol consumption <26.0 g/day (men)/<13.0 g/day (women); and no history of diabetes or CVD. Multivariate logistic regression was used to examine associations of nutrient/food intakes with LR. RESULTS: LR individuals reported higher intake of vegetable protein, fiber, magnesium, non-heme iron, potassium; lower energy intake; lower intake of cholesterol, saturated fatty acids, animal protein; and lower 24-h urinary sodium compared with individuals not LR. With regard to foods, LR individuals reported higher intake of fruits, vegetables, grains, pasta/rice, fish; lower intakes of meats, processed meats, high-fat dairy, and sugar-sweetened beverages than individuals not LR. CONCLUSIONS: Lower energy intake and differential intake of multiple specific nutrients and foods are characteristic of individuals at low risk for developing CVD. Identification of dietary habits associated with LR is important for further development of public health efforts aimed at reduction/prevention of CVD. PMID- 22057681 TI - The expression of PCNA, c-erbB-2, p53, ER and PR as well as atypical hyperplasia in tissues nearby the breast cancer. AB - To examine the proper margin for breast conservative surgery in Chinese women population. 40 breast cancer specimens were collected and each sample was dissected into several groups: primary tumor group, 1 cm paracarcinoma, 2 cm paracarcinoma, 3 cm paracarcinoma and excessive 3 cm paracarcinoma groups. The immunohistochemistry staining was performed to measure the expression levels of proliferating cell nuclear antigen (PCNA), c-erbB-2, p53, estrogen receptor (ER) and progesterone receptor (PR). The gene expressions of PCNA, c-erbB-2, and p53 gradually decreased with the increased distance from primary tumor (P < 0.05). The 1 and 2 cm paracarcinoma group (no differences between the two, P > 0.05) showed higher risk factors (c-erbB-2, p53) than the 3 cm and excessive 3 cm paracarcinoma groups (P < 0.05). The expression of PCNA, ER, and PR showed no correlation with cancer progression (P > 0.05). Beyond the paracarcinoma 2 cm distance, the tissues showed significant decreases in tumor gene expression, which could represent the appropriate region for breast conservative surgery. PMID- 22057682 TI - Induction of interferon-gamma contributes to Toll-like receptor 3-mediated herpes simplex virus type 1 inhibition in astrocytes. AB - Toll-like receptor 3 (TLR3) recognizes double-stranded RNA and induces type I interferon (IFN)-mediated antiviral immunity against a number of viral infections. Type III IFN (IFN-lambda) is a newly identified antiviral cytokine that has biological functions similar to those of type I IFNs. We thus investigated the role of IFN-lambda in TLR3 activation-mediated inhibition of herpes simplex virus type 1 (HSV-1) in human primary astrocytes. Human astrocytes express endogenous IFN-lambda1 and IFN-lambda receptor complex, interleukin-28 receptor alpha subunit (IL-28Ralpha), and IL-10Rbeta. The activation of TLR3 by poly-I:C treatment significantly induced the expression of IFN-lambda1 and IFN lambda2/3 in astrocytes. The induction of IFN-lambda contributed to TLR3 activation-mediated HSV-1 inhibition in astrocytes. Investigation of the mechanisms showed that treatment of astrocytes with specific antibody against IFN lambda receptor attenuated the anti-HSV-1 activity of poly-I:C, indicating that endogenous IFN-lambda contributes to the anti-HSV-1 effect of TLR3 activation. The anti-HSV-1 effect of endogenous IFN-lambda was also confirmed by the finding that recombinant IFN-lambda treatment inhibited HSV-1 infection of astrocytes. These results provide direct and compelling evidence that endogenous IFN-lambda participates in TLR3-mediated antiviral activity, which may have important implications in host cell innate immunity against HSV-1 infection in the CNS. PMID- 22057683 TI - A meta-analysis on the effect of corticosteroid therapy in Kawasaki disease. AB - The current recommended therapy for Kawasaki disease (KD) is the combination of intravenous immunoglobulin (IVIG) and aspirin. However, the role of corticosteroid therapy in KD remains controversial. Using meta-analysis, this study aimed to investigate the efficacy of corticosteroid therapy in KD by comparing it with standard IVIG and aspirin therapy. We included all related randomized and quasi-randomized controlled trials by searching Medline, the Cochrane Central Register of Controlled Trials, EMBASE, Pub Med, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and the Japanese database (Japan Science and Technology) as well as hand searches of selected references. Data collection and meta-analysis were performed to evaluate the effect of corticosteroids. Our search yielded 11 studies; 7 of which evaluated the effect of corticosteroid for primary therapy in KD, and 4 investigated the effect of corticosteroid therapy in IVIG-resistant patients. Meta-analysis of these studies revealed a significant reduction in the rates of initial treatment failure among patients who received corticosteroid therapy in combination with IVIG compared to IVIG alone (odds ratio (OR) = 0.50; 95% CI, 0.32~0.79; p = 0.003). Furthermore, the use of corticosteroids reduced the duration of fever and the time required for C-reactive protein to return to normal. Our data did not show any significant increase in the incidence of coronary artery lesions or coronary aneurysms (OR = 0.67; 95% CI, 0.35~1.28; p = 0.23) in the corticosteroid group. CONCLUSION: Corticosteroid combined with IVIG in primary treatment or as treatment of IVIG-resistant patients improved clinical course without increasing coronary artery lesions in children with acute KD. PMID- 22057684 TI - Mica, a potential two-dimensional-crystal gate insulator for organic field-effect transistors. AB - 2D mica crystals (with thickness < 100 nm) obtained by mechanical exfoliation are incorporated for the first time into the design of organic thin film field-effect transistor arrays and organic single crystal transistors as a gate insulator. The size of mica crystals could be up to the dimensions of an A4 piece of paper. All devices so fabricated exhibited high mobility and low operating voltage, indicating the high quality of the crystals and the great potential of mica crystals as a flexible, low-cost, transparent insulator for organic electronics. PMID- 22057685 TI - Patients with isolated prolonged in vitro bleeding time. Clinical symptoms. AB - In patients with isolated prolonged in vitro bleeding time there is no standardised treatment concept. With this study we characterized the extent of bleeding symptoms. PATIENTS, METHODS: All diagnoses known to cause prolonged in vitro bleeding time (PFA-100) (epinephrine-cartridge >160 s, ADP-cartridge > 120 s) have been excluded, such as platelet function disorders, effects of medications, nutrition or von Willebrand disease. 75 patients (77%, n = 58 women; 23%, n = 17 men, median age 46 (16-81) years were included. All bleeding symptoms have been stored in a databank with help of a comprehensive questionnaire. RESULTS: 78% (n = 54) of all patients reported of having had an operation, 69.8% (n = 37) of them described postoperative bleedings (p = 0.0373). 13.5% (n = 5) of the 54 could remember having been randomly treated by the administration of a transfusion and only 2.7% (n = 1) were treated by substitution of von Willebrand factor. 71% (n = 51) patients indicated haematoma (p = 0.8116). About 33.8% (n = 24) patients had gum bleeding and 40.8% (n = 29, p = 0.7808) patients reported bleeding after the dentist. 41.4% (n = 29) patients suffered under frequent epistaxis (p = 0.0212). There was no correlation between prolonged epinephrine bleeding time to VWF:Ag (rho = 0.16) nor to VWF:RCo (rho = 0.12) nor between prolonged epinephrine and ADP bleeding time (rho = 0.01) nor to ROTEM(r) analysis. CONCLUSION: Patients with isolated prolonged PFA are mainly women and can be affected by all kinds of bleedings while haematoma is the main symptom. VWD might not be causal. PMID- 22057686 TI - Solvent-free microextraction techniques in gas chromatography. AB - Microextraction techniques represent a major part of modern sample preparation in the analysis of organic micropollutants. This article provides a short overview of recent developments in solvent-free microextraction techniques. From the first open-tubular trap techniques in the mid-1980s to recent packed-needle devices, different implementations of in-needle packings for microextraction are discussed with their characteristic benefits, shortcomings and possible sampling modes. Special emphasis is placed on methods providing full automation and solvent exclusion. In this context, in-tube extraction and the needle trap are discussed, with an overview of current research on new sorbent materials, together with the requirements for more efficient method development. PMID- 22057687 TI - Low-dose cardiovascular computed tomography: where are the limits? AB - Since its introduction in the 1970s, diagnostic computed tomography (CT) imaging has grown rapidly and developed into a standard diagnostic test for a wide variety of cardiovascular conditions. Although this has undoubtedly led to improved medical care, it has also been associated with a significant increase in population-based radiation exposure and the potential downstream increase in cancer is a justified concern. For cardiovascular CT, new CT scanner technologies were initially directed toward maximizing image quality rather than minimizing radiation exposure. Only more recently have technologic advances yielded dose saving protocols for cardiovascular applications, with impressive reduction of radiation exposure. The achievable limits of population-based exposure are dependent on responsible, evidence-based use of CT for cardiovascular imaging as well as exploitation of available and emerging dose-saving strategies. PMID- 22057688 TI - Meeting review: cardiomyocyte regeneration and protection, La Jolla, California, June 2011. PMID- 22057689 TI - Role of antiplatelet therapy in secondary prevention of acute coronary syndrome. AB - Cardiovascular disease is one of the major causes of death in developed countries, mainly related to coronary artery disease and its acute complications. Platelets play a great role in the pathogenesis of acute thrombotic events of coronary artery disease when silent chronic disease becomes acutely symptomatic. Platelet importance in coronary artery disease and pathophysiology of acute events support the large benefit of antiplatelet agents for both acute management of ACS and secondary prevention. Recent developments in oral antiplatelet therapy raised questions about the choice of the molecules, the use of single or double therapy, and the optimal dosing and duration of treatment. The present review aims to provide a current appraisal of antiplatelet therapy use after ACS and to summarize available scientific evidence for an optimal use of antiplatelet agents in daily practice, including the new P2Y12 blockers. PMID- 22057690 TI - Intramolecular electron transfer in sulfite-oxidizing enzymes: probing the role of aromatic amino acids. AB - Sulfite oxidase (SO) is a molybdoheme enzyme that is important in sulfur catabolism, and mutations in the active site region are known to cause SO deficiency disorder in humans. This investigation probes the effects that mutating aromatic residues (Y273, W338, and H337) in the molybdenum-containing domain of human SO have on both the intramolecular electron transfer (IET) rate between the molybdenum and iron centers using laser flash photolysis and on catalytic turnover via steady-state kinetic analysis. The W338 and H337 mutants show large decreases in their IET rate constants (k (ET)) relative to the wild type values, suggesting the importance of these residues for rapid IET. In contrast, these mutants are catalytically competent and exhibit higher k (cat) values than their corresponding k (ET), implying that these two processes involve different conformational states of the protein. Redox potential investigations using spectroelectrochemistry revealed that these aromatic residues close to the molybdenum center affect the potential of the presumably distant heme center in the resting state (as shown by the crystal structure of chicken SO), suggesting that the heme may be interacting with these residues during IET and/or catalytic turnover. These combined results suggest that in solution human SO may adopt different conformations for IET and for catalysis in the presence of the substrate. For IET the H337/W338 surface residues may serve as an alternative docking site for the heme domain. The similarities between the mutant and wild type EPR spectra indicate that the active site geometry around the Mo(V) center is not changed by the mutations studied here. PMID- 22057691 TI - Altered IL-10 and TNF-alpha production in peripheral blood mononuclear cells of systemic lupus erythematosus patients after Toll-like receptor 2, 4, or 9 activation. AB - Toll-like receptor (TLR) activation and cytokines have been linked to the disease flare of systemic lupus erythematosus (SLE), yet the expression profiles of TLRs and cytokines in response to TLR activation in SLE patients remain unclear. In this study, we evaluated the expression levels of IL-10, TNF-alpha, interferon gamma (IFN-gamma), TLR-2, TLR-4, and TLR-9 in peripheral blood mononuclear cells (PBMCs) from SLE patients and normal controls after PBMCs were stimulated with a TLR-2, TLR-4, or TLR-9 agonist. The expression levels in SLE patient group were statistically compared with those in normal control group. It was found in SLE patients that the IL-10 protein production was down-regulated after the activation of TLR-2, TLR-4, or TLR-9 and that the TNF-alpha protein production was decreased after the activation of TLR-2 or TLR-9, but not TLR-4. However, the transcript levels of IL-10 and TNF-alpha as well as the protein and transcript levels of IFN-gamma were comparable between SLE and normal control groups. In addition, the TLR-2 transcript levels seem to be diminished after the activation of TLR-2, TLR-4, or TLR-9, but TLR-4 and TLR-9 transcript levels were not altered. The results indicate that the cytokine production from PBMCs in response to TLR activation is dysregulated in SLE patients, supporting the possibility that TLR activation may influence lupus disease activity through regulating cytokine production. PMID- 22057692 TI - ATPaceTM: injectable adenosine 5'-triphosphate : Diagnostic and therapeutic indications. AB - ATPaceTM, a novel injectable formulation of adenosine 5'-triphosphate (ATP), is developed by Cordex Pharma, Inc. (Cordex) as a diagnostic and therapeutic drug for the management of cardiac bradyarrhythmias. Extracellular ATP exerts multiple effects in various cell types by activating cell-surface receptors known as P2 receptors. In the heart, ATP suppresses the automaticity of cardiac pacemakers and atrioventricular (AV) nodal conduction via adenosine, the product of its degradation by ecto-enzymes, as well as by triggering a cardio-cardiac vagal reflex. ATP, given as a rapid intravenous bolus injection, has been used since the late 1940s as a highly effective and safe therapeutic agent for the acute termination of reentrant paroxysmal supraventricular tachycardia (PSVT) involving the AV node. In addition, preliminary studies have shown that ATP can also be used as a diagnostic agent for the identification of several cardiac disorders including sinus node dysfunction (sick sinus syndrome), dual AV nodal pathways, long QT syndrome, and bradycardic syncope. The US Food and Drug Administration has approved Cordex formulation for ATP as an Investigational New Drug and two pathways for its marketing approval; one therapeutic, i.e., acute termination of paroxysmal PSVT, and the other diagnostic, i.e., the identification of patients with bradycardic syncope who can benefit from pacemaker therapy. The scientific rationale for the development of ATPaceTM is discussed. PMID- 22057693 TI - Determination of the structures of small gold clusters on stepped magnesia by density functional calculations. AB - The structural modifications of small supported gold clusters caused by realistic surface defects (steps) in the MgO(001) support are investigated by computational methods. The most stable gold cluster structures on a stepped MgO(001) surface are searched for in the size range up to 24 Au atoms, and locally optimized by density-functional calculations. Several structural motifs are found within energy differences of 1 eV: inclined leaflets, arched leaflets, pyramidal hollow cages and compact structures. We show that the interaction with the step clearly modifies the structures with respect to adsorption on the flat defect-free surface. We find that leaflet structures clearly dominate for smaller sizes. These leaflets are either inclined and quasi-horizontal, or arched, at variance with the case of the flat surface in which vertical leaflets prevail. With increasing cluster size pyramidal hollow cages begin to compete against leaflet structures. Cage structures become more and more favourable as size increases. The only exception is size 20, at which the tetrahedron is found as the most stable isomer. This tetrahedron is however quite distorted. The comparison of two different exchange-correlation functionals (Perdew-Burke-Ernzerhof and local density approximation) show the same qualitative trends. PMID- 22057694 TI - Induction of point chirality by E/Z photoisomerization. PMID- 22057696 TI - An overview of nitrogen cycling in a semiarid savanna: some implications for management and conservation in a large African park. AB - Nitrogen (N) is a major control on primary productivity and hence on the productivity and diversity of secondary producers and consumers. As such, ecosystem structure and function cannot be understood without a comprehensive understanding of N cycling and dynamics. This overview describes the factors that govern N distribution and dynamics and the consequences that variable N dynamics have for structure, function and thresholds of potential concern (TPCs) for management of a semiarid southern African savanna. We focus on the Kruger National Park (KNP), a relatively intact savanna, noted for its wide array of animal and plant species and a prized tourist destination. KNP's large size ensures integrity of most ecosystem processes and much can be learned about drivers of ecosystem structure and function using this park as a baseline. Our overview shows that large scale variability in substrates exists, but do not necessarily have predictable consequences for N cycling. The impact of major drivers such as fire is complex; at a landscape scale little differences in stocks and cycling were found, though at a smaller scale changes in woody cover can lead to concomitant changes in total N. Contrasting impacts of browsers and grazers on N turnover has been recorded. Due to the complexity of this ecosystem, we conclude that it will be complicated to draw up TPCs for most transformations and pools involved with the N cycle. However, we highlight in which cases the development of TPCs will be possible. PMID- 22057697 TI - Tackling contentious invasive plant species: a case study of buffel grass in Australia. AB - Introduced plants that have both production values and negative impacts can be contentious. Generally they are either treated as weeds and their use prohibited; or unfettered exploitation is permitted and land managers must individually contend with any negative effects. Buffel grass (Cenchrus ciliaris) is contentious in Australia and there has been no attempt to broadly and systematically address the issues surrounding it. However, recent research indicates that there is some mutual acceptance by proponents and opponents of each others' perspectives and we contend that this provides the basis for a national approach. It would require thorough and on-going consultation with stakeholders and development of realistic goals that are applicable across a range of scales and responsive to regional differences in costs, benefits and socio-economic and biophysical circumstances. It would be necessary to clearly allocate responsibilities and ascertain the most appropriate balance between legislative and non-legislative mechanisms. A national approach could involve avoiding the introduction of additional genetic material, countering proliferation in regions where the species is sparse, preventing incursion into conservation reserves where it is absent, containing strategically located populations and managing communities to prevent or reduce dominance by buffel grass. This approach could be applied to other contentious plant species. PMID- 22057698 TI - [Intraoperative awareness: nightmare or harmless complication?]. PMID- 22057699 TI - Can we really use beta-lactam/beta-lactam inhibitor combinations for the treatment of infections caused by extended-spectrum beta-lactamase-producing bacteria? PMID- 22057700 TI - Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations. AB - BACKGROUND: Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence. METHODS: Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range). RESULTS: Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (<11%). Confounder-adjusted Cox regression confirmed that first-line EFV plus AZT (reference) was associated with a higher median hazard for resistance emergence, compared with other treatments: EFV plus TDF (hazard ratio [HR], 0.57; range, 0.42-0.76), LPV plus AZT (HR, 0.63; range, 0.45-0.89), LPV plus TDF (HR, 0.55; range, 0.33-0.83), ATZ/r plus TDF (HR, 0.43; range, 0.17-0.83). Two-thirds of resistance events were associated with detectable HIV RNA level <=500 copies/mL during treatment, and only one-third with virological failure (HIV RNA level, >500 copies/mL). CONCLUSIONS: The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of resistance emergence, most likely because of improved tolerability and pharmacokinetics resulting from a once-daily dosage. PMID- 22057701 TI - beta-Lactam/beta-lactam inhibitor combinations for the treatment of bacteremia due to extended-spectrum beta-lactamase-producing Escherichia coli: a post hoc analysis of prospective cohorts. AB - BACKGROUND: Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is an important cause of invasive infections. Alternatives to carbapenems- considered the drugs of choice--are needed because of the emergence of carbapenemase-producing enterobacteria. The efficacy of beta-lactam/beta-lactam inhibitors (BLBLI) in such infections is controversial. METHODS: The authors performed a post hoc analysis of patients with bloodstream infections due to ESBL EC from 6 published prospective cohorts. Mortality and length of hospital stay in patients treated with an active BLBLI (amoxicillin-clavulanic acid [AMC] and piperacillin-tazobactam [PTZ]) or carbapenem were compared in 2 cohorts: the empirical therapy cohort (ETC) and the definitive therapy cohort (DTC). Confounding was controlled by multivariate analysis; for patients in the ETC, a propensity score for receiving carbapenem was also used. RESULTS: The ETC included 103 patients (BLBLI, 72; carbapenem, 31), and the DTC included 174 (BLBLI, 54; carbapenem, 120). Mortality rates at day 30 for those treated with BLBLI versus carbapenems were 9.7% versus 19.4% for the ETC and 9.3% versus 16.7% for the DTC, respectively (P > .2, log-rank test). After adjustment for confounders, no association was found between either empirical therapy with BLBLI (adjusted hazard ratio [HR], 1.14; 95% confidence interval [CI], .29-4.40; P = .84) or definitive therapy (adjusted HR, 0.76; 95% CI, .28-2.07; P = .5) and increased mortality. Furthermore, BLBLI therapy, with respect to carbapenem, was not found to influence length of hospital stay. CONCLUSIONS: These results suggest that AMC and PTZ are suitable alternatives to carbapenems for treating patients with bloodstream infections due to ESBL-EC if active in vitro and would be particularly useful as definitive therapy. PMID- 22057702 TI - Clinical features and epidemiology of melioidosis pneumonia: results from a 21 year study and review of the literature. AB - BACKGROUND: Melioidosis is an important cause of community-acquired sepsis in Southeast Asia and northern Australia, and pneumonia is the most common presentation. Clinical manifestations range from acute fulminant sepsis to chronic infection mimicking tuberculosis. Pneumonia may be the primary presenting feature, or it can develop secondary to initial disease at a distant focus. METHODS: A prospective database of all melioidosis patients at Royal Darwin Hospital (Australia) between 1989 and 2010 was reviewed. RESULTS: Of 624 patients with culture-confirmed melioidosis, 319 (51%) presented with pneumonia as the primary diagnosis. Acute/subacute presentations accounted for the majority of primary pneumonia cases (91%); chronic disease was seen less commonly (9%). Secondary pneumonia developed in 20% of patients with other primary melioidosis presentations and was particularly common in those with positive blood cultures. Risk factors for presentation with primary pneumonia (compared with other primary presentations) were rheumatic heart disease or congestive cardiac failure, chronic obstructive pulmonary disease, smoking, and diabetes mellitus, with P < .05 for these conditions in a multivariate logistic regression model. Patients presenting with pneumonia more frequently developed septic shock (33% vs 10%; P < .001) and died (20% vs 8%; P <.001) compared with patients with other primary presentations. Multilobar disease occurred in 28% of primary pneumonia patients and was associated with greater mortality (32%) than in those with single-lobe disease (14%; P < .001). CONCLUSIONS: Melioidosis pneumonia is often a rapidly progressive illness with high mortality, particularly among those with multilobar disease. Risk factors have been identified, and early diagnosis and treatment should be priorities. PMID- 22057703 TI - Serology as an adjunct to polymerase chain reaction assays for surveillance of acute respiratory virus infections. PMID- 22057704 TI - Identification of false-positive QuantiFERON-TB Gold In-Tube assays by repeat testing in HIV-infected patients at low risk for tuberculosis. AB - The QuantiFERON-TB Gold In-Tube assay (QFT) is increasingly being used for latent tuberculosis screening in patients infected with human immunodeficiency virus (HIV) in the United States. This is a retrospective analysis of repeating positive QFT assays as a strategy to identify false-positive results in HIV infected patients at low risk for tuberculosis. PMID- 22057705 TI - Appropriate medical standards of crisis care. PMID- 22057706 TI - Creating a standardized system for allocation of scarce clinical resources in response to an all hazards mass casualty disaster. PMID- 22057707 TI - Surge capability: CHPTER and SC healthcare worker preparedness. PMID- 22057708 TI - Efficacy and safety of influenza vaccines. PMID- 22057709 TI - Influenza 2010-2011 in one South Carolina community: report of four cases in young adults and plea for wider immunization. PMID- 22057710 TI - Cost containment and policy changes for HIV services in a resource limited setting. PMID- 22057711 TI - All-hazards COOP for medical facilities. PMID- 22057712 TI - Is there much limited legal liability protection for physicians in crisis standards of care in SC? PMID- 22057713 TI - All hazards planning and response in the Veterans Administration. PMID- 22057714 TI - Dose dependence of intratumoral perivascular distribution of monoclonal antibodies. AB - Intravenously delivered antibodies have been previously found to distribute in a perivascular fashion in a variety of tumor types and despite targeting a range of different antigens. Properties of both the antibody and the targeted antigen, such as the administered dose, binding affinity, and antigen metabolic half-life, are predicted to influence the observed perivascular distribution. Here, the effect of antibody dose on the perivascular distribution is determined using an unbiased image analysis approach to quantify the microscopic distribution of the antibody around thousands of blood vessels per tumor. This method allows the quantitative determination of the localization of blood vessels, extravasated antibody, and tumor antigen following the administration of antibody doses covering two orders of magnitude in the dose range commonly utilized in preclinical studies. A mathematical model of antibody extravasation, diffusion, binding, and endocytosis in a Krogh cylinder geometry with parameters directly measured or taken from the literature is quantitatively consistent with the experimentally determined profiles. A previously reported scaling analysis is employed to extend these results to any tumor model in which the antigen density and turnover rate are known, allowing facile quantitative prediction of the minimum antibody dose required for complete tumor saturation. PMID- 22057715 TI - Spectroscopic analysis of immobilised redox enzymes under direct electrochemical control. AB - This article reviews recent developments in spectroscopic analysis of electrode immobilised enzymes under direct, unmediated electrochemical control. These methods unite the suite of spectroscopic methods available for characterisation of structural, electronic and coordination changes in proteins with the exquisite control over complex redox enzymes that can be achieved in protein film electrochemistry in which immobilised protein molecules exchange electrons directly with an electrode. This combination is particularly powerful in studies of highly active enzymes where redox states can be controlled even under fast electrocatalytic turnover. We examine examples in which UV-visible, IR, Raman and MCD spectroscopy have been combined with direct electrochemistry to probe redox dependent chemistry, and consider future opportunities for 'direct' spectroelectrochemistry of immobilised enzymes. PMID- 22057716 TI - Left ventricular remodeling in swine after myocardial infarction: a transcriptional genomics approach. AB - Despite the apparent appropriateness of left ventricular (LV) remodeling following myocardial infarction (MI), it poses an independent risk factor for development of heart failure. There is a paucity of studies into the molecular mechanisms of LV remodeling in large animal species. We took an unbiased molecular approach to identify candidate transcription factors (TFs) mediating the genetic reprogramming involved in post-MI LV remodeling in swine. Left ventricular tissue was collected from remote, non-infarcted myocardium, 3 weeks after MI-induction or sham-surgery. Microarray analysis identified 285 upregulated and 278 downregulated genes (FDR < 0.05). Of these differentially expressed genes, the promoter regions of the human homologs were searched for common TF binding sites (TFBS). Eighteen TFBS were overrepresented >two-fold (p < 0.01) in upregulated and 13 in downregulated genes. Left ventricular nuclear protein extracts were assayed for DNA-binding activity by protein/DNA array. Out of 345 DNA probes, 30 showed signal intensity changes >two-fold. Five TFs were identified in both TFBS and protein/DNA array analyses, which showed matching changes for COUP-TFII and glucocorticoid receptor (GR) only. Treatment of swine with the GR antagonist mifepristone after MI reduced the post-MI increase in LV mass, but LV dilation remained unaffected. Thus, using an unbiased approach to study post-MI LV remodeling in a physiologically relevant large animal model, we identified COUP-TFII and GR as potential key mediators of post-MI remodeling. PMID- 22057717 TI - TDP-43 toxicity is mediated by the unfolded protein response-unrelated induction of C/EBP homologous protein expression. AB - Transactive response DNA-binding protein-43 (TDP-43) neuronal toxicity plays an essential role in the pathogenesis of amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. In our previous study, we showed that low-grade overexpression of TDP-43, which is thought to mimic the gain-of-function of TDP-43, caused neuronal death, mediated by the upregulation of Bim and the downregulation of Bcl-xL in vitro. In this study, we show that TDP-43 overexpression caused the upregulation of C/EBP homologous protein (CHOP) and that disruption of the CHOP gene markedly attenuated TDP-43-induced cell death. These results indicate that increases in CHOP expression contribute to TDP-43-induced cell death. We also show that the TDP-43-induced upregulation of CHOP expression is mediated by both the upregulation of the mRNA level of CHOP and the attenuation of thedegradation of CHOP, which is independent on the PERK/eIF2alpha/ATF4 or other pathway related to the unfolded protein response (UPR) to endoplasmic reticulum stress. This study provides the first example of the CHOP-mediated cell death that is independent of the UPR. (c) 2011 Wiley Periodicals, Inc. PMID- 22057718 TI - On the stability of the bioactive flavonoids quercetin and luteolin under oxygen free conditions. AB - The natural flavonoid compounds quercetin (3,3',4',5,7-pentahydroxyflavone) and luteolin (3',4',5,7-tetrahydroxyflavone) are important bioactive compounds with antioxidative, anti-allergic, and anti-inflammatory properties. However, both are unstable when exposed to atmospheric oxygen, which causes degradation and complicates their analytical determinations. The oxidative change of these flavonoids was observed and followed by UV-visible spectrophotometry, both in aqueous and ethanolic solutions. The distribution of the degradation products in aqueous media was monitored by LC-MS and LC-DAD analysis. The amounts of oxidative reaction products increase with the exposure time. The oxidative degradation reduces the pharmacological efficiency of these antioxidants and renders analytical determination inaccurate. The oxidative changes in flavonoid test solutions can explain the inconsistent dissociation constants reported in the literature. Dissociation constants of quercetin and luteolin were determined both by alkalimetric titration and by UV-visible spectrophotometry under deaerated conditions. The values pK(1) = 5.87 +/- 0.14 and pK(2) = 8.48 +/- 0.09 for quercetin, and pK(1) = 5.99 +/- 0.32 and pK(2) = 8.40 +/- 0.42 for luteolin were found. PMID- 22057719 TI - Ultrasound-enhanced surfactant-assisted dispersive liquid-liquid microextraction and high-performance liquid chromatography for determination of ketoconazole and econazole nitrate in human blood. AB - A simple and efficient method, based on ultrasound-enhanced surfactant-assisted dispersive liquid-liquid microextraction (UESA-DLLME) followed by high performance liquid chromatography (HPLC) has been developed for extraction and determination of ketoconazole and econazole nitrate in human blood samples. In this method, a common cationic surfactant, cetyltrimethylammonium bromide (CTAB), was used as dispersant. Chloroform (40 MUL) as extraction solvent was added rapidly to 5 mL blood containing 0.068 mg mL(-1) CTAB. The mixture was then sonicated for 2 min to disperse the organic chloroform phase. After the extraction procedure, the mixture was centrifuged to sediment the organic chloroform phase, which was collected for HPLC analysis. Several conditions, including type and volume of extraction solvent, type and concentration of the surfactant, ultrasound time, extraction temperature, pH, and ionic strength were studied and optimized. Under the optimum conditions, linear calibration curves were obtained in the ranges 4-5000 MUg L(-1) for ketoconazole and 8-5000 MUg L( 1) for econazole nitrate, with linear correlation coefficients for both >0.99. The limits of detection (LODs, S/N = 3) and enrichment factors (EFs) were 1.1 and 2.3 MUg L(-1), and 129 and 140 for ketoconazole and econazole nitrate, respectively. Reproducibility and recovery were good. The method was successfully applied to the determination of ketoconazole and econazole nitrate in human blood samples. PMID- 22057720 TI - Ultra-thin layer MALDI mass spectrometry of membrane proteins in nanodiscs. AB - Nanodiscs have become a leading technology to solubilize membrane proteins for biophysical, enzymatic, and structural investigations. Nanodiscs are nanoscale, discoidal lipid bilayers surrounded by an amphipathic membrane scaffold protein (MSP) belt. A variety of analytical tools has been applied to membrane proteins in nanodiscs, including several recent mass spectrometry studies. Mass spectrometry of full-length proteins is an important technique for analyzing protein modifications, for structural studies, and for identification of proteins present in binding assays. However, traditional matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry methods for analyzing full-length membrane proteins solubilized in nanodiscs are limited by strong signal from the MSP belt and weak signal from the membrane protein inside the nanodisc. Herein, we show that an optimized ultra-thin layer MALDI sample preparation technique dramatically enhances the membrane protein signal and nearly completely eliminates the MSP signal. First-shot MALDI and MALDI imaging are used to characterize the spots formed by the ultra-thin layer method. Furthermore, the membrane protein enhancement and MSP suppression are shown to be independent of the type of membrane protein and are applicable to mixtures of membrane proteins in nanodiscs. PMID- 22057721 TI - Data processing for image-based chemical sensors: unsupervised region of interest selection and background noise compensation. AB - Natural olfaction suggests that numerous replicas of small sensors can achieve large sensitivity. This concept of sensor redundancy can be exploited by use of optical chemical sensors whose use of image sensors enables the simultaneous measurement of several spatially distributed indicators. Digital image sensors split the framed scene into hundreds of thousands of pixels each corresponding to a portion of the sensing layer. The signal from each pixel can be regarded as an independent sensor, which leads to a highly redundant sensor array. Such redundancy can eventually be exploited to increase the signal-to-noise ratio. In this paper we report an algorithm for reduction of the noise of pixel signals. For this purpose, the algorithm processes the output of groups of pixels whose signals share the same time behavior, as is the case for signals related to the same indicator. To define these groups of pixels, unsupervised clustering, based on classification of the indicator colors, is proposed here. This approach to signal processing is tested in experiments on the chemical sensitivity of replicas of eight indicators spotted on to a plastic substrate. Results show that the groups of pixels can be defined independently of the geometrical arrangement of the sensing spots, and substantial improvement of the signal-to-noise ratio is obtained, enabling the detection of volatile compounds at any location on the distributed sensing layer. PMID- 22057722 TI - Iron topochemistry and surface reactivity of amphibole asbestos: relations with in vitro toxicity. AB - Chemical reactivity of asbestos tremolite from Italy and USA localities and Union Internationale Contre le Cancer (UICC) crocidolite was studied in relation to Fe content, oxidation state, and structural coordination. Direct correlation between amount of Fe(2+) at the exposed M(1) and M(2) sites of the amphibole structure and fiber chemical reactivity was established. The in vitro toxicity of the same samples was investigated on human alveolar A549 cell line. Relationship between crystal-chemical features and cell toxicity is not straightforward. UICC crocidolite has Fe content and chemical reactivity largely higher than that of tremolite samples, but all show comparable in vitro toxic potential. Results obtained evidenced that Fe topochemistry is not a primary factor for induced cell toxicity, though it accounts for asbestos chemical reactivity (and possibly genotoxicity). PMID- 22057724 TI - mTOR-rictor is the Ser473 kinase for AKT1 in mouse one-cell stage embryos. AB - Mammalian target of rapamycin (mTOR) controls cell growth and proliferation via the raptor-mTOR (TORC1) and rictor-mTOR (TORC2) protein complexes. The mTORC2 containing mTOR and rictor is thought to be rapamycin insensitive and it is recently shown that both rictor and mTORC2 are essential for the development of both embryonic and extra embryonic tissues. To explore rictor function in the early development of mouse embryos, we disrupted the expression of rictor, a specific component of mTORC2, in mouse fertilized eggs by using rictor shRNA. Our results showed that one-cell stage eggs that were lack of rictor could not enter into the two-cell stage normally. Recent biochemical studies suggests that TORC2 is the elusive PDK2 (3'-phosphoinositide-dependent kinase 2) for AKT/PKB Ser473 phosphorylation, which is deemed necessary for AKT function, so we microinjected AKT-S473A into mouse fertilized eggs to investigate whether AKT-S473A is downstream effector of mTOR.rictor to regulate the mitotic division. Our findings revealed that the rictor induced phosphorylation of AKT in Ser473 is required for TORC2 function in early development of mouse embryos. PMID- 22057725 TI - Clinical evaluation of the OptiVisTM multifocal intraocular lens. AB - INTRODUCTION: The purpose of this study was to evaluate the efficacy of the OptiVisTM Multifocal Intraocular Lens (IOL) in patients undergoing bilateral crystalline lens replacement following extracapsular extraction by phacoemulsification. METHODS: This was a prospective 6-month, open-label, nonrandomized clinical trial of subjects undergoing bilateral implantation with the OptiVis Multifocal IOL. Of the 121 eyes enrolled, 88 eyes of 44 subjects completed the entire 6-month trial. RESULTS: After 6 months, the majority of eyes had a distance best-corrected visual acuity of 20/20 or better, with 89.8% achieving that outcome, and 100% with 20/32 or better. At an intermediate distance, most eyes (90.9%) had a distance corrected intermediate visual acuity of 20/40 or better, and 53.4% had an acuity of 20/32 or better. At a near distance, most eyes (95.5%) had a distance corrected near visual acuity of 20/40 or better by month 6. The most commonly reported adverse event was mild-to moderate halos (n = 30, 36%) and mild-to-moderate glare (n = 15, 18%). In addition, there was one case of cystoid macular edema, one posterior capsular opacification, and one case of severe corneal edema. Postoperative contrast sensitivity was comparable with normal phakic subjects >= 60 years of age. CONCLUSION: The OptiVis Multifocal IOL provided satisfactory visual acuity at distance, near, and intermediate with no apparent reduction in contrast sensitivity. Additional, longer-term follow-up studies are planned. PMID- 22057726 TI - Effects of escitalopram on sleep problems in patients with major depression or generalized anxiety disorder. AB - INTRODUCTION: Disturbed sleep is a key symptom in major depressive disorder (MDD) and generalized anxiety disorder (GAD). First-line antidepressants, including the selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs), may have different effects on sleep. METHODS: Data from 22 randomized, controlled trials comparing escitalopram with SSRIs, SNRIs, or placebo in the treatment of adult MDD or GAD were included. Both last observation carried forward (LOCF) and repeated measurements (MMRM) were used to analyze the sleep item of the Montgomery Asberg Depression Rating Scale (MADRS) or Hamilton Anxiety Rating Scale (HAM-A) after 8 weeks of treatment. Sleep related treatment-emergent adverse events were also compared across groups. RESULTS: For patients with MDD (n = 5133), the treatment difference on MADRS item 4 ("reduced sleep") was significantly in favor of escitalopram versus placebo (LOCF [P = 0.0017] and MMRM [P = 0.0002]), versus SSRIs (LOCF [P = 0.0020] and MMRM [P < 0.0031]), and versus SNRIs (LOCF [P = 0.0002] and MMRM [P = 0.0352]). For the 53% of patients with MDD who suffered from sleep problems at baseline (baseline MADRS item 4 score >= 4), the improvement in sleep symptoms was significantly in favor of escitalopram versus placebo (LOCF [P = 0.0022] and MMRM [P < 0.0005]), versus SSRIs (LOCF [P = 0.0001] and MMRM [P = 0.0002]), and versus SNRIs (LOCF [P < 0.0067] but not MMRM [P > 0.0787]). For patients with GAD (n = 2052) the treatment difference in sleep symptoms measured by HAM-A item 4 ("insomnia") was significantly in favor of escitalopram versus placebo (LOCF [P = 0.0005] and MMRM [P < 0.0001]), but not different to paroxetine or venlafaxine. The same pattern was seen for the large proportion (67%-82%) of GAD patients reporting sleep problems at baseline (baseline HAM-A item 4 score >= 2). In MDD, the rate of insomnia as an adverse event after escitalopram was higher than placebo, similar to SSRIs, and lower than SNRIs. CONCLUSIONS: Additional research assessing the comparative effects of antidepressants with polysomnography is needed. In the interim, from a clinical perspective, escitalopram appears to be beneficial for the treatment of sleep problems in MDD and GAD. PMID- 22057727 TI - Oseltamivir in seasonal, pandemic, and avian influenza: a comprehensive review of 10-years clinical experience. AB - Oseltamivir (Tamiflu(r); F. Hoffmann-La Roche Ltd, Basel, Switzerland) is an orally administered antiviral for the treatment and prevention of influenza A and B infections that is registered in more than 100 countries worldwide. More than 83 million patients have been exposed to the product since its introduction. Oseltamivir is recommended by the World Health Organization (WHO) for use in the clinical management of pandemic and seasonal influenza of varying severity, and as the primary antiviral agent for treatment of avian H5N1 influenza infection in humans. This article is a nonsystematic review of the experience gained from the first 10 years of using oseltamivir for influenza infections since its launch in early 2000, emphasizing recent advances in our understanding of the product and its clinical utility in five main areas. The article reviews the pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate, including information on special populations such as children and elderly adults, and the co-administration of oseltamivir with other agents. This is followed by a summary of data on the effectiveness of oseltamivir treatment and prophylaxis in patients with all types of influenza, including pandemic (H1N1) 2009 and avian H5N1 influenza. The implications of changes in susceptibility of circulating influenza viruses to oseltamivir and other antiviral agents are also described, as is the emergence of antiviral resistance during and after the 2009 pandemic. The fourth main section deals with the safety profile of oseltamivir in standard and special patient populations, and reviews spontaneously reported adverse event data from the pandemic and pre-pandemic periods and the topical issue of neuropsychiatric adverse events. Finally, the article considers the pharmacoeconomics of oseltamivir in comparison with vaccination and usual care regimens, and as a component of pandemic influenza mitigation strategies. PMID- 22057729 TI - Dissolution and pharmacokinetics of a novel micronized aspirin formulation. AB - Aspirin (acetylsalicylic acid, ASA) has been used as an analgesic, antipyretic and antiinflammatory drug for many years. A new 500 mg aspirin tablet formulation containing micronized active ingredient and an effervescent component has been developed for potential improvement in the onset of action for acute pain treatment. This paper describes the dissolution and the pharmacokinetics of the new formulation in comparison with regular aspirin tablets, aspirin granules and aspirin effervescent tablets. Micronized aspirin tablets dissolve significantly faster over a pH range from 1.2 to 6.8 compared to regular 500 mg aspirin tablets. Plasma concentration time curve comparison to regular 500 mg aspirin tablets showed a substantial improvement in the time to maximum plasma concentrations (T(max)) (ASA 17.5 min vs. 45 min) and an increase in maximum plasma concentration (C(max)) (ASA 13.8 MUg/ml vs. 4.4 MUg/ml) while the overall extent of exposure (AUC) remains almost unchanged. The data suggest a potential improvement for onset of action in treating acute pain with the new micronized aspirin formulation. PMID- 22057730 TI - Water ingestion reduces skin blood flow through sympathetic vasoconstriction. AB - OBJECTIVE: Water ingestion induces a pressor effect in patients with efferent baroreflex impairment and a mild pressor effect in elderly healthy subjects. However, water raised the total peripheral vascular resistance (TPR) without a prominent change in blood pressure in young healthy subjects. We try to investigate whether water elicits a cardiovascular response via regulating regional skin blood flow (SkBF) in young healthy subjects. METHODS: In a randomized, controlled, crossover fashion, 15 healthy male subjects (19-27 years old) ingested either 500 (water session) or 50 ml of water (control). The heart rate, blood pressure, cardiac index, and TPR were measured using a Task Force Monitor. A laser Doppler velocimeter was used to determine the change in the SkBF at the left thenar eminence. Plasma catecholamines and their metabolites were also measured. RESULTS: At 25 min after ingestion of 500 ml water, the cardiac index and SkBF significantly decreased compared to control. In contrast, the TPR significantly increased after ingestion of 500 ml water. Plasma dihydroxyphenylalanine significantly increased at 25 min after water. INTERPRETATION: Water ingestion decreases the cardiac index to compensate for the increase in the TPR, leading to no net change in blood pressure in young healthy subjects. This study suggests that water decreases the SkBF, a mechanism that might account partly for the nature of osmopressor response to water in young healthy subjects. PMID- 22057731 TI - Replacing a battery by a nanogenerator with 20 V output. PMID- 22057732 TI - How to determine post-RCHOP therapy for risk-tailored adult patients with diffuse large B-cell lymphoma, addition of maintenance rituximab or observation: multicenter experience. AB - BACKGROUND: In international prognostic index (IPI) risk-tailored adult patients with diffuse large B-cell lymphoma (DLBCL), it is still unclear whether the addition of maintenance rituximab (MR) improves progression-free (PFS) and overall survival (OS), after RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. METHODS: In our study, 207 patients (age: 21 59 years) received six 14-day cycles of RCHOP and gained overall response. After RCHOP, 98 patients were enrolled in the observation (OBS) arm. 109 patients continued to receive MR therapy. RESULTS: In IPI risk <2 profile, PFS at 5 years reached 72.9% (MR arm) versus 56% (OBS arm) (P = 0.033). In IPI risk >=2 profile, PFS estimation at 5 years was 44.9% (MR arm) versus 33.5% (OBS arm) (P = 0.006). It is noteworthy that patients with IPI >=2 who received MR achieved PFS similar to that for patients in the OBS arm with the IPI <2, 44.9% versus 56% (P = 0.97). In patients with an IPI <2, OS at 5 years was 83.2% (MR arm) versus 81.2% (OBS arm) (P = 0.708). In patients with an IPI >=2, 5-year OS estimation was 44.6% (MR arm) versus 40.5% (OBS arm) (P = 0.067). Subgroup analysis of patients with an IPI >=3 risk profile shows a survival benefit for patients receiving MR. OS at 5 years was 62% (MR arm) versus 49% (OBS arm), (P = 0.033). CONCLUSIONS: In conclusion, maintenance rituximab after RCHOP improves progression-free survival. In addition, overall survival is improved for patients with an IPI >=3 risk profile receiving MR. PMID- 22057733 TI - The effects of vascular endothelial growth factor C knockdown in esophageal squamous cell carcinoma. AB - PURPOSE: We investigated the role of vascular endothelial growth factor C (VEGF C) in esophageal squamous cell carcinoma (ESCC) by knocking down VEGF-C expression in the ESCC cell line EC9706. METHODS: Immunohistochemistry and in situ hybridization techniques were used to detect the expression of VEGF-C expression in ESCC tissues. We also investigated the relationship between VEGF-C expression and lymph node metastasis. We designed a siRNA expression plasmid for VEGF-C and transfected it into EC9706 cells. Stable clones were selected, and VEGF-C expression was analyzed by RT-PCR and western blotting. Cells were inoculated into nude mice. The expression of VEGF-C in the resulting tumors was analyzed by immunohistochemistry and in situ hybridization. RESULTS: VEGF-C is highly expressed in ESCC and correlated with lymph node metastasis, as high levels were observed in patients presenting with lymph node metastases relative to those who did not (P < 0.01). Transfection with VEGF-C-siRNA decreased the expression of VEGF-C mRNA and protein. ESCC cells stably transfected with VEGF-C siRNA expressed very low levels of VEGF-C (P < 0.01 compared with control). This knockdown effect persisted when the cells were inoculated into nude mice and allowed to form tumors. CONCLUSIONS: The siRNA-targeted knockdown of VEGF-C led to a significant reduction in VEGF-C expression. This siRNA technique could be used for gene therapy in ESCC. PMID- 22057734 TI - Projected and observed diabetes epidemics in China and beyond. AB - Diabetes is one of the major noncommunicable diseases found worldwide. Different researchers have reported the predicted and observed prevalence of diabetes and the number of people with diabetes over different years in China and in other countries. This review provides a new insight into the growing epidemic of diabetes in recent decades and in the coming future by comparing projected and observed prevailing trends of this disease reported in the international literature. The review found that the projected burden of diabetes for China in each time point from 2000 to 2030 underestimated the epidemic of diabetes in terms of the prevalence and the total number of people with the disease. Based on a recent Chinese national survey, the observed prevalence and the total number of people with diabetes in 2008 (9.7% and 92.4 million, respectively) were remarkably higher than that expected for 2009 or 2010 (3.9% and 53.1 million for 2009, and 4.5% and 43.2 million for 2010).The observed 2008 figures were even much higher than the projected prevalence and the number of people with diabetes for 2030. The tendency to underestimate future diabetes epidemics also occurs in many other countries, especially those characterized by low and middle incomes. PMID- 22057735 TI - Editorial: Learning from top performers using a positive deviance approach. PMID- 22057736 TI - Inhibitor-immunology-study. Evaluation of inhibitor development in haemophilia B. AB - The development of inhibitors in haemophilia B is one of the most important complications of replacement therapy, affecting mortality and morbidity. Inhibitor development is based on complex immunological factors, and to date, only little is known about its underlying mechanisms. Here, we present first results of the haemophilia B group of our Inhibitor-Immunology study. PATIENTS, METHODS: So far we have analysed 15 patients with haemophilia B. Four of them developed a high titre inhibitor; the remaining 11 had no inhibitor. We evaluated 9 SNPs in 8 genes (CD40, CTLA-4 , IL-1beta, IL-10, TLR2 , TLR4, TLR9, TNF-alpha). We compared the distribution of these alleles between inhibitor and non-inhibitor haemophilia B patients and between haemophilia B patients and a normal male control population. HLA typing was performed in all patients. Results, discussion: There appears to be a trend towards a skewed distribution of TLR 9, IL-10 and CTLA4 alleles in haemophilia B patients. Due to the limited number these differences are, however, not statistically significant. The t-test of all patients with inhibitor versus without inhibitor was significant for HLA-A*03 and DPB1*0401 and borderline for DRB1*0201. PMID- 22057737 TI - Spontaneous femoral neck fracture associated with a low serum level of vitamin D. PMID- 22057738 TI - Arthroscopic gap distance can predict the degree of scapholunate ligament tears: a cadaver study. AB - BACKGROUND: Midcarpal joint arthroscopy is essential for diagnosing scapholunate (SL) instability, but a discrepancy may exist between the grade of arthroscopic evaluation and the extent of SL ligament tears. This study aimed to investigate whether the magnitude of arthroscopic SL gap distance could predict the extent of ligamentous disruptions in a simulated SL dissociation model. METHODS: Eight upper extremities of fresh cadavers were analyzed. Static and dynamic SL gap distances were measured with using custom-made probes via midcarpal arthroscopy in intact wrists following sequential sectioning of the SL stabilizing ligaments. Comparisons of static and dynamic SL gaps between stages were conducted using analysis of variance followed by the Games-Howell test. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic performance of the SL gap distance in identifying simulated ligament tears. RESULTS: There were no significant differences between stages in the static SL gap distance. Dynamic SL gap distance increased significantly following SL interosseous ligament (SLIL) sectioning. According to the ROC curve for dynamic SL gap distance, the area under the curve was 0.94 for the assessment of the diagnostic performances in identifying complete SLIL sectioning. A cut-off value of 1.4 mm for the dynamic SL gap showed the highest diagnostic accuracy rate (91%). The dynamic SL gap distance showed a high diagnostic performance in the detection of dorsal intercarpal ligament (DICL) sectioning. The highest accuracy rate (85%) was noted when the threshold value was set at 2.8 mm. CONCLUSION: The SLIL is the primary stabilizer of the SL joint in the viewpoint of arthroscopic measurement. Dynamic SL joint widening of more than 1.4 mm showed the best predictive ability for complete SLIL tears, while 2.8 mm widening made it possible to predict both DICL and SLIL tears. PMID- 22057739 TI - Transition-metal-catalyzed synthesis of diboranes(4). AB - The diboranes(4) bis(catecholato)diborane (B(2)Cat(2)) and bis(pinacolato)diborane (B(2)Pin(2)) are important precursors for organoboronic esters, which are versatile reagents for the formation of carbon-carbon bonds. A new catalytic synthesis for these compounds starts from catecholborane or pinacolborane and gives the dehydrocoupling products B(2)Cat(2) and B(2)Pin(2) with turnover numbers of up to 11,600 (see scheme). PMID- 22057740 TI - Good things in small packages: meeting the challenges of a lower volume congenital heart surgery program. PMID- 22057741 TI - Changes in cardiothoracic surgery education. PMID- 22057742 TI - Cardiac transplantation at MUSC: 24 years of experience and change. PMID- 22057743 TI - The development of a minimally invasive cardiac surgery program: the Greenville experience. PMID- 22057744 TI - The survival benefit of lung transplantation among patients with advanced pulmonary diseases. PMID- 22057745 TI - Experience with valve-sparing aortic root replacement at MUSC. PMID- 22057746 TI - The evolving role of thoracoscopic lobectomy for non-small cell lung cancer. PMID- 22057747 TI - Brain death, cardiac death, and the dead donor rule. PMID- 22057748 TI - Stem cells and cardiac surgery- the road ahead. PMID- 22057749 TI - Mitral valve repair with the american correction: the first 100 cases at Roper Hospital. PMID- 22057750 TI - Update on ventricular assist devices. PMID- 22057751 TI - Apicoaortic Conduits, an innovative solution to difficult aortic stenosis: the MUSC Experience. PMID- 22057752 TI - Systematic review of met and unmet need of surgical disease in rural sub-Saharan Africa. AB - BACKGROUND: Little is known about the burden of surgical disease in rural sub Saharan Africa, where district and rural hospitals are the main providers of care. The present study sought to analyze what is known about the met and unmet need of surgical disease. METHODS: The PubMed and EMBASE databases were searched for studies of surveys in rural areas, information on surgical admissions, and operations performed within rural and district hospitals. Data were extrapolated to calculate the amount of surgical disease per 100,000 population and the number of operations performed per 100,000 population. These extrapolations were used to estimate the total, the met, and the unmet need of surgical disease. RESULTS: The estimated overall incidence of nonfatal injury is at least 1,690/100,000 population per year. Morbidity as a result of injury is up to 190/100,000 population per year, and the annual mortality from injury is 53-92/100,000. District hospitals perform 6 fracture reductions (95% CI: 0.1-12)/100,000 population per year and 14 laparotomies (95% CI: 7-21)/100,000 per year. The incidence of peritonitis and bowel obstruction is unknown, although it may be as high as 1,364/100,000 population for the acute abdomen. The annual total need for inguinal hernia repair is estimated to be a minimum of 205/100,000 population. The average district hospital performs 30 hernia repairs (95% CI: 18-41)/100,000 population per year, leaving an unmet need of 175/100,000 population annually. CONCLUSIONS: District hospitals are not meeting the surgical needs of the populations they serve. Urgent intervention is required to build up their capacity, to train healthcare personnel in safe surgery and anesthesia, and to overcome obstacles to timely emergency care. PMID- 22057753 TI - Comparison of Limberg flap and tension-free primary closure during pilonidal sinus surgery. AB - BACKGROUND: Pilonidal disease is an inflammatory disease seen in the intergluteal region. In this study, our aim was to compare the efficacy of the Limberg flap versus a tension-free primary closure. METHODS: A total of 93 patients were included in this study. The patients were assigned consecutively by the closed envelope technique to one of two groups: 49 patients in group 1 (excision and Limberg flap) and 44 patients in group 2 (tension-free primary closure). Excision and reconstruction with the Limberg flap was performed in its classic form. For tension-free primary closure after excision of the sinus tract with an elliptical incision, the skin and subcutaneous tissue were released 2-3 cm away from the incision line. The subcutaneous tissue was closed twofold with 2/0 polyglactin sutures. The skin underwent 3/0 polypropylene mattress suturing. RESULTS: The median age was 25 years (17-43 years). The median follow-up period was 29.5 months (8-43 months). There was no significant difference between the groups in terms of age, sex, follow-up time, or anesthesia method. One patient in each group experienced wound infection. During the first 6 months of follow-up there was no recurrence. However, at later visits recurrences were seen in two patients in each group (4.1% in group 1, 4.5% in group 2). CONCLUSIONS: The lower rates of wound infection and recurrence associated with the Limberg flap reported elsewhere may be associated with healing of the tension-free procedure. In this study, tension-free primary closure was found to be as effective as the Limberg flap reconstruction. PMID- 22057754 TI - Incidence of malignancy in thyroid nodules determined to be follicular lesions of undetermined significance on fine-needle aspiration. AB - BACKGROUND: Fine-needle aspiration (FNA) for thyroid nodules is the most important method for determining a diagnosis. The system for reporting results is based on a cytopathologic classification that stratifies the risk of malignancy. METHODS: We retrospectively studied 197 patients who underwent FNA for diagnostic evaluation of a thyroid nodule and had their results reported as a follicular lesion of undetermined significance (FLUS) using the Bethesda classification system. The objective of the study was to analyze the incidence and histopathologic types of malignancy in these cases. RESULTS: The final histopathologic breakdown is as follows: 65 cases (32.9%) of follicular adenoma, 81 cases (41.1%) of microfollicular adenomatoid nodule, 19 cases (9.6%) of microfollicular adenomatoid nodule on the background of thyroiditis, 17 cases (8.6%) of follicular carcinoma, 9 cases (4.6%) of follicular variant papillary carcinoma, and 6 cases (3.1%) of classic papillary carcinoma, for a 16.2% incidence of malignancy. Beyond these diagnoses in the FNA-biopsied nodules, we observed 29 cases (14.7%) of incidental ipsilateral papillary thyroid microcarcinoma (PTM) and 13 cases (6.6%) of incidental contralateral thyroid lobe PTM. CONCLUSIONS: This study observed a 16.2% incidence of thyroid cancer in the nodule designated FLUS compared to the 5 to 15% rate reported by the Bethesda FNA classification. The overall incidence of incidental PTM in the thyroid gland was 21.3%. These data support considering surgical intervention for at least diagnostic purposes in a patient with the FNAB diagnosis of FLUS. PMID- 22057755 TI - Spontaneous adrenal hemorrhage with associated masses: etiology and management in 6 cases and a review of 133 reported cases. AB - BACKGROUND: Spontaneous adrenal hemorrhage associated with a mass is uncommon and treatment strategies are not standardized. Current treatment modalities range from supportive management and blood transfusion to embolization or immediate operative extirpation. Our objectives were to describe six cases from a single institution and to perform a literature review of the etiology of the condition and recommended management of patients with hemorrhagic adrenal masses. METHODS: Records from six patients diagnosed with adrenal hemorrhage and an associated mass at a single institution were reviewed. Clinical records and outcomes were analyzed. A comprehensive review of 133 reported cases in the literature was performed. RESULTS: Six patients presented with spontaneous adrenal hemorrhage that appeared to be associated with a mass, with tumor sizes ranging from 3.7 to 15 cm. Three patients underwent adrenalectomy for pheochromocytoma or adrenocortical cancer. Three patients did not undergo adrenalectomy: one had a metastasis from lung cancer, one underwent embolization, and one had resolution of the mass on interval imaging. A comprehensive review of the literature identified 133 cases, with pheochromocytoma the most commonly reported lesion (48%). CONCLUSIONS: Spontaneous adrenal hemorrhage is rare. When it does occur, a high level of suspicion for malignant disease or pheochromocytoma should be maintained. The possibility of a hematoma masquerading as a neoplasm should also be considered. In cases of ongoing hemorrhage, embolization may be a lifesaving temporizing measure. Acute surgical intervention should be considered in selected patients, and surgery may not be required in all patients. A cautious approach with a comprehensive biochemical and imaging work-up is advised prior to operation. PMID- 22057756 TI - Relation of lipid gene scores to longitudinal trends in lipid levels and incidence of abnormal lipid levels among individuals of European ancestry: the Atherosclerosis Risk in Communities (ARIC) study. AB - BACKGROUND: Multiple genetic loci have been associated with blood lipid levels. We tested the hypothesis that persons with an unfavorable lipid gene profile would experience a greater increase in lipid levels and a higher incidence of abnormal lipid levels relative to those with more-favorable lipid gene profiles. METHODS AND RESULTS: A total of 9328 individuals of European descent (aged 45-64 years) in the ARIC (Atherosclerosis Risk in Communities) study were followed for 9 years. Separate gene scores were created for each lipid phenotype on the basis of 95 loci identified in a published genome-wide association study of >100 000 people of European-descent. Adjusted linear and survival models were used to estimate associations with lipid levels and incidence of lipid-lowering medication or abnormal lipid levels. Age and sex interactions were also explored. The cross-sectional difference (mg/dL) per 1 SD was -1.89 for high-density lipoprotein cholesterol (HDL-C), 9.5 for low-density lipoprotein cholesterol (LDL C), and 22.8 for triglycerides (P<5*10(-34) for all). Longitudinally, overall triglyceride levels rose over time, and each 1-SD greater triglyceride gene score was associated with an average increase in triglyceride levels of 0.3 mg/dL (P=0.003) over 3 years. The HDL-C, LDL-C, and total cholesterol gene scores were not related to change. All lipid gene scores were positively related to incidence of abnormal lipid levels over follow-up (hazard ratios per SD range, 1.15-1.36). CONCLUSIONS: Associations of genetic variants with lipid levels over time are complex. The triglyceride gene score was positively related to change in triglycerides levels, but similar longitudinal results were not observed for LDL C or HDL-C levels. Unfavorable gene scores were nevertheless related to higher incidence of abnormal levels. PMID- 22057757 TI - Quality of colonoscopy: the real need is for universal quality measurement and common standards for certification and credentialing. PMID- 22057759 TI - Reflux disease and Barrett's esophagus. PMID- 22057760 TI - Endoscopic diagnosis and treatment of upper gastrointestinal tumors. AB - Early diagnosis, endoscopic differentiation of benign from malignant lesions, and removal of clinically significant tumors are increasingly considered to be major topics of interest in the upper gastrointestinal tract. This interest is mainly due to the development of better imaging tools and new resection techniques that fulfill surgical criteria. At this year's Digestive Disease Week (DDW; 7-10 May 2011, Chicago, Illinois, USA), more than 500 abstracts were presented that focused on better imaging, training, safety issues, luminal stenting, and indications and results in endoscopic submucosal dissection (ESD). This review highlights a selection of clinically relevant reports of the upper gastrointestinal tract, excluding Barrett's esophagus, which is covered in a separate report. Related abstracts that are not discussed in this review can be found in the additional references of interest. PMID- 22057761 TI - Gastrointestinal bleeding. AB - Gastrointestinal bleeding remains one of the most important emergencies in gastroenterology. Despite this, only about 100 abstracts concerning gastrointestinal bleeding (excluding bleeding complicating endoscopic procedures) were presented at this year's Digestive Disease Week (DDW; 7-10 May 2011; Chicago, Illinois, USA), accounting for less than 2% of all presented lectures and posters. It seems that the number of such abstracts has been decreasing over recent years. This may be due in part to the high level of medical care already achieved, especially in the areas of pharmacotherapy and endoscopic treatment of gastrointestinal bleeding. In this review of gastrointestinal bleeding, priority has been given to large epidemiological studies reflecting "real life," and abstracts dealing more or less directly with endoscopic management. PMID- 22057762 TI - Small-bowel endoscopy. PMID- 22057763 TI - Colon tumors and colonoscopy. AB - A large number of abstracts dealing with colonoscopy were presented at Digestive Disease Week (DDW; 7-10 May 2011; Chicago, Illinois, USA). Topics included: new techniques in colonoscopy, recent innovations in endoscopic ultrasonography (EUS), prevention of postpolypectomy bleeding, Raman spectroscopy, bowel preparation during colonoscopy, risk factors for high grade dysplasia (HGD) in colonic adenoma, recent advances in endoscopic treatment of colorectal cancer (CRC), and follow-up of HGD and CRC after endoscopic treatment. This review focuses on the most relevant presentations dealing with colon tumours and colonoscopy. PMID- 22057764 TI - Endoscopic retrograde cholangiopancreatography. PMID- 22057765 TI - The year of improved tissue acquisition, randomized trials, and endoscopic ultrasound-guided therapy. AB - Presentations at this year's Digestive Disease Week (DWW; 7-10 May, 2011; Chicago, Illinois, USA) reflected a very active year for endoscopic ultrasound (EUS). There were numerous abstracts on EUS-guided fine-needle aspiration (FNA) and core biopsy to improve tissue acquisition, improve diagnostic accuracy, and indeed go beyond routine cytology and tissue diagnosis. EUS-guided therapy including drainage, anastomoses, injection of therapeutic agents, and ablation were other common themes with a lot of new information presented, much of which was obtained from randomized trials. This review discusses in detail some of the abstracts that followed a common theme. Additional interesting abstracts on this topic are listed at the end of the review. PMID- 22057766 TI - Natural orifice transluminal endoscopic surgery. PMID- 22057768 TI - Is cold biopsy forceps resection of diminutive polyps really so inadequate? PMID- 22057770 TI - Peroral direct cholangioscopy with an ultraslim gastroscope in combination with a short double-balloon enteroscope for reconstructed biliary anatomy. PMID- 22057771 TI - The optimal timing for urgent endoscopy in nonvariceal upper gastrointestinal bleeding. PMID- 22057773 TI - Endoscopic rendezvous technique and esophageal fistulae: sometimes it is worth working in the dark! PMID- 22057776 TI - DNA polymerase-beta mediates the neurogenic effect of beta-amyloid protein in cultured subventricular zone neurospheres. AB - beta-Amyloid protein (Abeta) is thought to be responsible for neuronal apoptosis in Alzheimer's disease (AD). Paradoxically, Abeta can also promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells (NPCs) to differentiate into neurons. However, the mechanisms of Abeta-induced neurogenesis are unknown. Here we examined the role of DNA polymerase-beta (DNA pol-beta), a DNA repair enzyme that is required for proper neurogenesis during brain development and is also responsible for Abeta-induced neuronal apoptosis. In neurospheres obtained from the adult mouse subventricular zone (SVZ), the knockdown of DNA pol-beta or its pharmacological blockade showed that the enzyme functioned both to repress proliferation of early nestin(+) progenitor cells and to promote the maturation of TuJ-1(+) neuronal cells. In neurospheres challenged with oligomers of synthetic Abeta(42) , the expression levels of DNA pol-beta were rapidly increased. DNA pol-beta knockdown prevented the Abeta(42) -promoted differentiation of nestin(+) progenitor cells into nestin(+) /Dlx-2(+) neuroblasts. Moreover, when neurospheres were seeded to allow full differentiation of their elements, blockade of DNA pol-beta prevented Abeta(42) induced differentiation of progenitors into MAP-2(+) neurons. Thus, our data demonstrate that Abeta(42) arrests the proliferation of a subpopulation of nestin(+) cells via the induction of DNA pol-beta, thereby allowing for their differentiation toward the neuronal lineage. Our findings reveal a novel role of DNA pol-beta in Abeta(42) -induced neurogenesis and identify DNA pol-beta as a key mechanistic link between the neurogenic effect of Abeta(42) on NPCs and the proapoptotic effect of Abeta(42) on mature neurons. PMID- 22057777 TI - Changes in expression profiles of antioxidant enzymes in diabetic rat kidneys. AB - BACKGROUND: In diabetes mellitus, increased formation of reactive oxygen species due to high level of glucose in both blood plasma and tissues creates oxidative stress and damages the tissues. Antioxidants together with the antioxidant enzymes are very important in order to protect the cells against oxidative damage. METHODS: Differential expressions of both mRNA and proteins of major antioxidant enzymes in streptozotocin-induced diabetic rat kidneys were measured with the help of real-time polymerase chain reaction and western blot analysis, respectively. Furthermore, effects of two strong antioxidants alpha-lipoic acid, vitamin C and their combination on the regulation of both expressions and the activities of antioxidant enzymes were also studied. RESULTS: In diabetic rat kidney tissue, both catalase and glutathione peroxidase activities were reduced (although mRNA expression for both was greatly increased) when compared with controls. No significant change was observed in superoxide dismutase (SOD) activity. Alpha-lipoic acid increased catalase activity towards the control values. Combined administration of alpha-lipoic acid and vitamin C increased the activities of both catalase and SOD, demonstrating a posttranslational effect. Glutathione concentrations were decreased in diabetic kidney; alpha-lipoic acid treatment partially restored the glutathione levels. CONCLUSIONS: All data showed the importance of post-transcriptional and translational regulation of the antioxidant enzyme activities against oxidative stress that is associated with diabetes. PMID- 22057779 TI - The position of nitrogen in N-heteropentacenes matters. AB - An exploratory study on novel silylethynylated N-heteropentacenes, which have their N atoms on the terminal rings of the pentacene backbone, is reported. This study leads to both p- and n-channel organic thin-film transistors with high field-effect mobility and also reveals that the position of the N atoms plays an important role in tuning the structures and properties of organic semiconductors based on N-heteropentacenes. PMID- 22057780 TI - Prosaccade errors in the antisaccade task: differences between corrected and uncorrected errors and links to neuropsychological tests. AB - The relations among spatial memory, Stroop-like colour-word subtests, and errors on antisaccade and memory-guided saccadic eye-movement trials for older and younger adults were tested. Two types of errors in the antisaccade task were identified: short latency prosaccade errors that were immediately corrected and longer latency uncorrected prosaccade errors. The age groups did not differ on percentages of either corrected or uncorrected errors, but the latency and time to correct prosaccade errors were shorter for younger than older adults. Uncorrected prosaccade errors correlated significantly with spatial memory accuracy and errors on the colour-word subtests, but neither of these neuropsychological indices correlated with corrected prosaccade errors. These findings suggest that uncorrected prosaccade errors may be a result of cognitive factors involving a failure to maintain the goal of the antisaccade task in working memory. In contrast, corrected errors may be a consequence of a fixation system involving an initial failure to inhibit a reflexive prosaccade but with active goal maintenance enabling correction to take place. PMID- 22057781 TI - Hypnotizability-dependent accuracy in the reproduction of haptically explored paths. AB - The study assessed differences between highly (Highs) and low hypnotizable (Lows) subjects in the blindfolded reproduction of paths connected at acute or obtuse angles. Reproduction attempts were made after path exploration performed by one finger, with or without concomitant cognitive activities (mental computation or imagery of exploring an angle larger than the explored one). The variables analyzed were: subjective experience (scores of the exploring effort, reproduction difficulty, perceived accuracy of reproduction, attention to mental computation and efficacy of imagery), exploration time, relative error in reproduction (under or overestimation) and the percentage of "successful" trials (absolute error <10 degrees ). The results showed that the subjective experience of exploration/reproduction and the exploration times are similar in Highs and Lows and that all subjects underestimate the explored angles and reproduce the acute angle more accurately than the obtuse one. Exploration of the acute angle concomitant with imagery of a larger one reduced its underestimation in both groups. Highs exhibited a larger number of successful trials after exploration of the obtuse angle, while Lows (males) decreased their relative error in the reproduction of the acute angle. In conclusion, in the more demanding condition of reproducing an obtuse angle, the Highs' reproduction was more accurate and more independent of cognitive load than that of the Lows. PMID- 22057782 TI - What happens in the lab does not stay in the lab [corrected]: Applying midstream modulation to enhance critical reflection in the laboratory. AB - In response to widespread policy prescriptions for responsible innovation, social scientists and engineering ethicists, among others, have sought to engage natural scientists and engineers at the 'midstream': building interdisciplinary collaborations to integrate social and ethical considerations with research and development processes. Two 'laboratory engagement studies' have explored how applying the framework of midstream modulation could enhance the reflections of natural scientists on the socio-ethical context of their work. The results of these interdisciplinary collaborations confirm the utility of midstream modulation in encouraging both first- and second-order reflective learning. The potential for second-order reflective learning, in which underlying value systems become the object of reflection, is particularly significant with respect to addressing social responsibility in research practices. Midstream modulation served to render the socio-ethical context of research visible in the laboratory and helped enable research participants to more critically reflect on this broader context. While lab-based collaborations would benefit from being carried out in concert with activities at institutional and policy levels, midstream modulation could prove a valuable asset in the toolbox of interdisciplinary methods aimed at responsible innovation. PMID- 22057783 TI - Exploration of signals of positive selection derived from genotype-based human genome scans using re-sequencing data. AB - We have investigated whether regions of the genome showing signs of positive selection in scans based on haplotype structure also show evidence of positive selection when sequence-based tests are applied, whether the target of selection can be localized more precisely, and whether such extra evidence can lead to increased biological insights. We used two tools: simulations under neutrality or selection, and experimental investigation of two regions identified by the HapMap2 project as putatively selected in human populations. Simulations suggested that neutral and selected regions should be readily distinguished and that it should be possible to localize the selected variant to within 40 kb at least half of the time. Re-sequencing of two ~300 kb regions (chr4:158Mb and chr10:22Mb) lacking known targets of selection in HapMap CHB individuals provided strong evidence for positive selection within each and suggested the micro-RNA gene hsa-miR-548c as the best candidate target in one region, and changes in regulation of the sperm protein gene SPAG6 in the other. PMID- 22057784 TI - Selective tau tyrosine nitration in non-AD tauopathies. AB - Previously, we reported the characterization of two novel antibodies that react with tau nitrated at tyrosine 197 (Tau-nY197) and tyrosine 394 (Tau-nY394) in Alzheimer's disease (AD). In this report, we examined whether tau nitration at these sites also occurs in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and Pick's disease (PiD), three neurodegenerative tauopathies that contain abundant tau deposits within glial and neuronal cell types but lack amyloid deposition. The reactivity of these antibodies was also compared to two previously characterized antibodies Tau-nY18 and Tau-nY29, specific for tau nitrated at tyrosine 18 and tyrosine 29, respectively. In the present experiments, Tau-nY18 did not label the classical pathological lesions of CBD or PSP but did label the neuronal lesions associated with PiD to a limited extent. In contrast, Tau-nY29 revealed some, but not all classes of tau inclusions associated with both CBD and PSP but did label numerous Pick body inclusions in PiD. Tau-nY197 was restricted to the neuropil threads in both CBD and PSP; however, similar to Tau-nY29, extensive Pick body pathology was clearly labeled. Tau-nY394 did not detect any of the lesions associated with these disorders. In contrast, extensive neuronal and glial tau pathology within these diseases was labeled by Tau-Y197, a monoclonal antibody that reacts within the Y 197-containing proline-rich region of the molecule. Based on our Western and IHC experiments, it appears that nitration of tau at tyrosine 29 is a pathological modification that might be associated with neurodegeneration. Collectively, our data suggest that site-specific tau tyrosine nitration events occur in a disease and lesion-specific manner, indicating that nitration appears to be a highly controlled modification in AD and non-AD tauopathies. PMID- 22057785 TI - Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples. AB - The diagnosis of medulloblastoma likely encompasses several distinct entities, with recent evidence for the existence of at least four unique molecular subgroups that exhibit distinct genetic, transcriptional, demographic, and clinical features. Assignment of molecular subgroup through routine profiling of high-quality RNA on expression microarrays is likely impractical in the clinical setting. The planning and execution of medulloblastoma clinical trials that stratify by subgroup, or which are targeted to a specific subgroup requires technologies that can be economically, rapidly, reliably, and reproducibly applied to formalin-fixed paraffin embedded (FFPE) specimens. In the current study, we have developed an assay that accurately measures the expression level of 22 medulloblastoma subgroup-specific signature genes (CodeSet) using nanoString nCounter Technology. Comparison of the nanoString assay with Affymetrix expression array data on a training series of 101 medulloblastomas of known subgroup demonstrated a high concordance (Pearson correlation r = 0.86). The assay was validated on a second set of 130 non-overlapping medulloblastomas of known subgroup, correctly assigning 98% (127/130) of tumors to the appropriate subgroup. Reproducibility was demonstrated by repeating the assay in three independent laboratories in Canada, the United States, and Switzerland. Finally, the nanoString assay could confidently predict subgroup in 88% of recent FFPE cases, of which 100% had accurate subgroup assignment. We present an assay based on nanoString technology that is capable of rapidly, reliably, and reproducibly assigning clinical FFPE medulloblastoma samples to their molecular subgroup, and which is highly suited for future medulloblastoma clinical trials. PMID- 22057786 TI - Pathology of immune reconstitution inflammatory syndrome in multiple sclerosis with natalizumab-associated progressive multifocal leukoencephalopathy. AB - Natalizumab is an approved medication for highly active multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) may occur as a severe side effect of this drug. Here, we describe pathological and radiological characteristics of immune reconstitution inflammatory syndrome (IRIS), which occurs in natalizumab-associated PML after the cessation of therapy, and we differentiate it from ongoing PML. Brain biopsy tissue and MRI scans from five MS patients with natalizumab-associated PML were analyzed and their histology compared with non-MS PML. Histology showed an extensive CD8-dominated T cell infiltrate and numerous macrophages within lesions, and in nondemyelinated white and grey matter, in four out of five cases. Few or no virally infected cells were found. This was indicative of IRIS as known from HIV patients with PML. Outstandingly high numbers of plasma cells were present as compared to non-MS PML and typical MS lesions. MRI was compatible with IRIS, revealing enlarging lesions with a band-like or speckled contrast enhancement either at the lesion edge or within lesions. Only the fifth patient showed typical PML pathology, with low inflammation and high numbers of virally infected cells. This patient showed a similar interval between drug withdrawal and biopsy (3.5 months) to the rest of the cohort (range 2.5-4 months). MRI could not differentiate between PML associated IRIS and ongoing PML. We describe in detail the histopathology of IRIS in natalizumab-associated PML. PML-IRIS, ongoing PML infection, and MS exacerbation may be impossible to discern clinically alone. MRI may provide some clues for distinguishing different pathologies that can be differentiated histologically. In our individual cases, biopsy helped to clarify diagnoses in natalizumab-associated PML. PMID- 22057787 TI - Parkin, PINK1 and mitochondrial integrity: emerging concepts of mitochondrial dysfunction in Parkinson's disease. AB - Mitochondria are dynamic organelles which are essential for many cellular processes, such as ATP production by oxidative phosphorylation, lipid metabolism, assembly of iron sulfur clusters, regulation of calcium homeostasis, and cell death pathways. The dynamic changes in mitochondrial morphology, connectivity, and subcellular distribution are critically dependent on a highly regulated fusion and fission machinery. Mitochondrial function, dynamics, and quality control are vital for the maintenance of neuronal integrity. Indeed, there is mounting evidence that mitochondrial dysfunction plays a central role in several neurodegenerative diseases. In particular, the identification of genes linked to rare familial variants of Parkinson's disease has fueled research on mitochondrial aspects of the disease etiopathogenesis. Studies on the function of parkin and PINK1, which are associated with autosomal recessive parkinsonism, provided compelling evidence that these proteins can functionally interact to maintain mitochondrial integrity and to promote clearance of damaged and dysfunctional mitochondria. In this review we will summarize current knowledge about the impact of parkin and PINK1 on mitochondria. PMID- 22057788 TI - Embryonal tumor with abundant neuropil and true rosettes (ETANTR) with loss of morphological but retained genetic key features during progression. PMID- 22057789 TI - Ocular decompression retinopathy following post-trabeculectomy suture lysis and management with triamcinolone acetonide. AB - Ocular decompression retinopathy (ODR) is a rare complication of sudden lowering of intraocular pressure (IOP) in glaucoma and ocular hypertension. An 80-year male, a known case of chronic open-angle glaucoma for 13 years, had his IOP controlled by multiple topical antiglaucoma medications. There was an increase in IOP, progression of optic disc cupping and visual field loss along with cataract over the past 6 months. The patient underwent uneventful phacoemulsification with posterior chamber intraocular lens (PCIOL) and penetrating trabeculectomy. Postoperatively, the trabeculectomy bleb was flat and IOP was 44 mmHg and was not controlled by bleb massage. Bleb needling and suture lysis were performed after 2 weeks. The IOP dropped from 44 to 6 mmHg. Three days later the patient presented with a sudden decline in visual acuity (VA) from 0.5 to 1.225 logMAR. The fundus showed multiple retinal haemorrhages resembling ODR. Choroidal detachment also occurred after 3 weeks. Optical coherence tomography confirmed the presence of macular oedema which was treated with an orbital floor triamcinolone acetonide injection (OFTA). The haemorrhages, choroidal detachment and macular oedema resolved and VA improved in 6 months. This is the first case report of ODR following suture lysis and needling after an uneventful combined phacoemulsification with PCIOL implant and trabeculectomy. It also highlights the role of OFTA injections in the management of ODR. PMID- 22057790 TI - Dramatic dysesthetic overhanging bleb. AB - We report on a patient with an overhanging bleb several years following trabeculectomy surgery with mitomycin C. PMID- 22057791 TI - Magnetic nanoparticles catalyzed synthesis of diverse N-heterocycles. AB - A large library of diversified compounds (pyrano [2,3-d]pyrimidines, pyrido[2,3 d] pyrimidines and a variety of spirooxindoles) were synthesized through a very efficient, economical and environmentally benign process utilizing magnetic nanoparticles. Ease of recovery using an external magnetic field is an additional ecofriendly attribute of this catalytic system. Most of the compounds are new; therefore, could be further explored for their pharmaceutical application. Moreover, column chromatography and recrystallisation of the products is not required as the crude products are already highly pure and hence can be used for target oriented synthesis on a wide scale. PMID- 22057792 TI - Ricin and Shiga toxins: effects on host cell signal transduction. AB - Shiga toxins and ricin are potent inhibitors of protein synthesis. In addition to causing inhibition of protein synthesis, these toxins activate proinflammatory signaling cascades that may contribute to the severe diseases associated with toxin exposure. Treatment of cells with Shiga toxins and ricin have been shown to activate a number of signaling pathways including those associated with the ribotoxic stress response, Nuclear factor kappa B activation, inflammasome activation, the unfolded protein response, mTOR signaling, hemostasis, and retrograde trafficking. In this chapter, we review our current understanding of these signaling pathways as they pertain to intoxication by Shiga toxins and ricin. PMID- 22057793 TI - A photogrammetric method to evaluate nutritional status without capture in habituated free-ranging Japanese macaques (Macaca fuscata): a pilot study. AB - The quantification of nutritional status (e.g., total body fat) of animals is difficult, because the linear dimension (body length) required for the calculation of proxy parameters, such as the physique or body mass indices, cannot be measured without capture. One solution is photogrammetry of body length, provided the following two criteria are met: (1) the camera axes and subject are oriented vertically, and (2) anatomical landmarks are easily identified with low measurement error. By modifying Mori's (Primates 20:371-397, 1979) approach, we devised an accurate photogrammetric method that uses a horizontal bar with an attached ruler for the monkey to traverse, and the anatomical landmarks of the eye and upper border of the ischial callosity to measure body length. We tested the applicability of this method on 11 adult female, habituated, free-ranging Japanese macaques (Macaca fuscata). Somatometric body length (crown-rump length and anterior trunk length) was statistically compared with the body length obtained using photogrammetry. The significant correlation of the photogrammetric body length with each somatometric measurement verified that the former could be employed to calculate various indices that are used to characterize fat mass (nutritional status) in Japanese macaques. The advantages and disadvantages of photogrammetry are also discussed. PMID- 22057794 TI - Three-dimensional reconstruction of soft palate modeling from subject-specific magnetic resonance imaging data. AB - PURPOSE: The objectives of this study were to extract a computational three dimensional (3D) soft palate model from a set of magnetic resonance imaging (MRI) data and to identify an approach that generates a patient-specific model in a computerized visual platform. METHODS: Multiple MRI slices of the head and neck region of a young, non-overweight Caucasian male volunteer were taken in the supine position with a passive oral appliance in place. The DICOM (Digital Imaging and Communications) MRI slices were registered into a high-resolution volumetric data set for manually segmentation to generate a surface mesh and, with additional editing, a volume mesh. For biomechanical dynamic simulation and for physical simulation of the anatomical structures, the volume mesh format and multiple landmarks of each muscle were imported into ArtiSynth, a 3D biomechanical modeling toolkit. RESULTS: The segmented soft palate complex consisted of five groups of muscles: levator veli palatini, tensor veli palatini, palatoglossus, palatopharyngeous and musculus uvulae. The palatine tonsil between the pharyngopalatine and glossopalatine arches was included in the segmentation. CONCLUSIONS: The same procedure was used to build up a generic reference model of the dentition, tongue, mandible and airway from a mixture of medical records (CT and dental casts) of the same subject. This manual segmentation method eliminated the common errors that occur from an automatic segmentation although it was more time-consuming. It remains a fundamental process for analyzing the dynamic interaction between anatomical components in the oral, pharyngeal, and laryngeal areas. PMID- 22057795 TI - Liquid-crystalline hybrid materials based on [60]fullerene and bent-core structures. AB - What a core-ker! By the appropriate combination of promesogenic bent-core structures and the C(60) unit, lamellar polar liquid-crystal phases were induced. The supramolecular organization of the functional fullerene-based assemblies, the temperature range of the soft phase, the stabilization of the mesophase-like order at room temperature, and the molecular switching under an electric field can be tuned, depending on the molecular structure. PMID- 22057796 TI - [Analysis of muscle function with kinetic superficial EMG in children with haemophilia - recognizing subclinical changes, establishing individual therapy, quality control]. AB - Electromyography (EMG) measures muscle electricity. It depends on muscle contraction and central motor control. Muscles react very sensitive on external signals (e. g. bleeding), The resulting changes can be shown in EMG. PATIENTS, METHODS: A first study included 51 children and young adults from Costa Rica. They underwent a clinical examination and EMG of the hip, knee and ankle joints. Resting muscle tone, maximal isometric contraction and three typical isotonic movements of the joints were measured. First step of analysis was to characterize typical pathogenic changes in the muscles and to find a corresponding physical therapy to minimize these changes. RESULTS: It showed that EMG is a good marker for muscle condition. It helps to individualize therapy and improve effectivity of physical and physiotherapeutic treatment of the locomotive system of children and young adults with hemophilia. It can help to recognize early subclinical changes and to control the outcome of therapeutic modalities. PMID- 22057797 TI - An aberrant cerebellar artery originating from the internal carotid artery. AB - The aberrant origin of the cerebellar arteries from anterior cerebral circulation is a quite rare vascular variation. Herein, we report a 52-year-old white female with angiographically occult subarachnoid hemorrhage. Left superior and anterior inferior cerebellar arteries were not detected. An aberrant cerebellar artery was noted to arise from the left cavernous internal carotid artery and terminated in the distribution of the ipsilateral superior and anterior inferior cerebellar arteries. This variant artery might likely have resulted from an abnormal regression of fetal anterior-to-posterior circulation connections, and may represent a fetal-type cerebellar artery. A review of the anatomy and clinical significance of the variant is presented. PMID- 22057798 TI - Anatomical classification of the shape and topography of the stomach. AB - The aim of the study was to present the classification of anatomical variations of the stomach, based on the radiological and historical data. In years 2006 2010, 2,034 examinations of the upper digestive tract were performed. Normal stomach anatomy or different variations of the organ shape and/or topography without any organic radiologically detectable gastric lesions were revealed in 568 and 821 cases, respectively. Five primary groups were established: abnormal position along longitudinal (I) and horizontal axis (II), as well as abnormal shape (III) and stomach connections (IV) or mixed forms (V). The first group contains abnormalities most commonly observed among examined patients such as stomach rotation and translocation to the chest cavity, including sliding, paraesophageal, mixed-form and upside-down hiatal diaphragmatic hernias, as well as short esophagus, and the other diaphragmatic hernias, that were not found in the evaluated population. The second group includes the stomach cascade. The third and fourth groups comprise developmental variations and organ malformations that were not observed in evaluated patients. The last group (V) encloses mixed forms that connect two or more previous variations. PMID- 22057799 TI - Recent South Carolina AHEC Family Practice Residency Program graduates. PMID- 22057800 TI - Well child care in infancy and health care costs birth-six years for South Carolina Medicaid children. PMID- 22057801 TI - Personalized lung cancer treatment based on molecular determinants. PMID- 22057802 TI - What awaits tomorrow's medical graduates: perfect bliss or perfect storm? PMID- 22057803 TI - Preserving principle without impeding progress. PMID- 22057805 TI - The silence of the lambs. PMID- 22057804 TI - First World Congress on ultrasound in medical education hosted by the University of South Carolina School of Medicine. PMID- 22057806 TI - Going forth with PRIDE: the Graduating Oath Ceremony Address to the MUSC Class of 2009. PMID- 22057807 TI - Docosahexaenoic acid modulates inflammatory and antineurogenic functions of activated microglial cells. AB - The complex process of microglial activation encompasses several functional activation states associated either with neurotoxic/antineurogenic or with neurotrophic/proneurogenic properties, depending mainly on the extent of activation and the nature of the activating stimuli. Several studies have demonstrated that acute exposure to the prototypical activating agent lipopolysaccharide (LPS) confers antineurogenic properties upon microglial cells. Acutely activated microglia ortheir conditioned media (CM) reduce neural stem progenitor cell (NPC) survival and prevent NPC differentiation into neurons. The present study tested the hypothesis that docosahexaenoic acid (DHA), a long-chain polyunsatured fatty acid (L-PUFA) with potent immunomodulatory properties, could dampen microglial proinflammatory functions and modulate their antineurogenic effect. We demonstrate that DHA dose dependently inhibits the synthesis of inflammatory products in activated microglia without inducing an alternative antiinflammatory phenotype. Among the possible DHA mechanisms of action, we propose the inhibition of p38 MAPK phosphorylation and the activation of the nuclear receptor peroxisome proliferator activated receptor (PPAR)-gamma. The attenuation of M1 proinflammatory phenotype has relevant consequences for the survival and differentiation of NPC, because DHA reverses the antineurogenic activities of conditioned media from LPS-activated microglia. Our study identifies new relevant potentially protective and proneurogenic functions of DHA, exerted through the modulation of microglial functions, that could be exploited to sustain or promote neuroregenerative processes in damaged/aged brain. PMID- 22057809 TI - Paradoxical response in ocular bartonellosis. PMID- 22057810 TI - Corticosteroid-sparing therapy: practice patterns among uveitis specialists. AB - PURPOSE: This study aims to determine uveitis specialists' practice patterns, preferences, and perceptions of corticosteroid-sparing therapies for the initial treatment of chronic noninfectious uveitis. METHODS: A survey was distributed to the American Uveitis Society and Proctor email listservs in order to restrict the respondents to specialists who likely have extensive experience in the use of immunomodulatory therapy. Topics included effectiveness, usage, and preferences related to seven immunomodulatory treatments. RESULTS: Among the 45 responders, the majority (59%) had greater than 10 years of experience treating uveitis. Methotrexate was the most commonly used initial therapy for anterior, intermediate, and posterior/panuveitis (85%, 57%, and 37%), and the most preferred for anterior (55%). Mycophenolate mofetil was the most preferred for intermediate (35%) and posterior/panuveitis (42%). Primary reasons not to prescribe a treatment were effectiveness for azathioprine, safety/tolerability for cyclosporine and cyclophosphamide, and a mixture of cost, safety/tolerability, and difficulty of administration for the biologic drugs. CONCLUSIONS: Within the group of highly experienced uveitis specialists, methotrexate is still the most commonly used initial treatment. Although newer biologic drugs are seen as effective, they are not commonly used, or even preferred, as initial corticosteroid-sparing treatment. PMID- 22057812 TI - The inhibitory effect of honokiol, a natural plant product, on vestibular schwannoma cells. AB - OBJECTIVES/HYPOTHESIS: As the molecular biology of vestibular schwannoma (VS) is better understood, new means of targeting the pathways involved for intervention in schwannoma cells are being developed. Honokiol, a bioactive constituent of Magnolia officinalis, has attracted attention due to its diverse biological effects. This study was conducted to determine the inhibitory effect of honokiol on schwannoma cell proliferation. METHODS: HEI 193 cells were used to investigate the growth-inhibitory effects of honokiol. Cell proliferation was assessed by MTT assays. Apoptosis was measured by flow cytometry analysis and immunofluorescence staining including Hoechst 33342 and TUNEL. Western blot analysis was used to assess the potential inhibition of extracellular signal-regulated kinase (ERK) and AKT signaling by honokiol. RESULTS: Honokiol exhibited significant antiproliferative activity in a dose-dependent manner on HEI 193 cells. Significant apoptosis was detected on schwannoma cells with 7 mg/mL(IC50) honokiol. Western blot analysis showed significant inhibition of ERK phosphorylation. CONCLUSIONS: Honokiol, a low molecular weight natural product, inhibits cell proliferation and promotes apoptosis in schwannoma cells by targeting the ERK pathway. Our data suggest that honokiol can be evaluated as a chemotherapeutic agent for VS. PMID- 22057811 TI - Environment-dependent long-range structural distortion in a temperature-sensitive point mutant. AB - Extensive environment-dependent rearrangement of the helix-turn-helix DNA recognition region and adjacent L-tryptophan binding pocket is reported in the crystal structure of dimeric E. coli trp aporepressor with point mutation Leu75Phe. In one of two subunits, the eight residues immediately C-terminal to the mutation are shifted forward in helical register by three positions, and the five following residues form an extrahelical loop accommodating the register shift. In contrast, the second subunit has wildtype-like conformation, as do both subunits in an isomorphous wildtype control structure. Treated together as an ensemble pair, the distorted and wildtype-like conformations of the mutant apoprotein agree more fully than either conformation alone with previously reported NOE measurements, and account more completely for its diverse biochemical and biophysical properties. The register-shifted segment Ile79-Ala80 Thr81-Ile82-Thr83 is helical in both conformations despite low helical propensity, suggesting an important structural role for the steric constraints imposed by beta-branched residues in helical conformation. PMID- 22057813 TI - The distributions of "new" and "old" Alu sequences in the human genome: the solution of a "mystery". AB - The distribution in the human genome of the largest family of mobile elements, the Alu sequences, has been investigated for the past 30 years, and the vast majority of Alu sequences were shown to have the highest density in GC-rich isochores. Ten years ago, it was discovered, however, that the small "youngest" (most recently transposed) Alu families had a strikingly different distribution compared with the "old" families. This raised the question as to how this change took place in evolution. We solved what was considered to be a "mystery" by 1) revisiting our previous results on the integration and stability of retroviral sequences, and 2) assessing the densities of acceptor sites TTTT/AA in isochore families. We could conclude 1) that the open state of chromatin structure plays a crucial role in allowing not only the initial integration of retroviral sequences but also that of the youngest Alu sequences, and 2) that the distribution of old Alus can be explained as due to Alu sequences being unstable in the GC-poor isochores but stable in the compositionally matching GC-rich isochores, again in line with what happens in the case of retroviral sequences. PMID- 22057814 TI - Structural water in carbonated hydroxylapatite and fluorapatite: confirmation by solid state (2)H NMR. AB - Water is well recognized as an important component in bone, typically regarded as a constituent of collagen, a pore-filling fluid in bone, and an adsorbed species on the surface of bone crystallites. The possible siting and role of water within the structure of the apatite crystallites have not been fully explored. In our experiments, carbonated hydroxyl- and fluorapatites were prepared in D(2)O and characterized by elemental analysis, thermal gravimetric analysis, powder X-ray diffraction, and infrared and Raman spectroscopy. Two hydroxylapatites and two fluorapatites, with widely different amounts of carbonate were analyzed by solid state (2)H NMR spectroscopy using the quadrupole echo pulse sequence, and each spectrum showed one single line as well as a low-intensity powder pattern. The relaxation time of 7.1 ms for 5.9 wt% carbonated hydroxylapatite indicates that the single line is likely due to rapid, high-symmetry jumps in translationally rigid D(2)O molecules, indicative of structural incorporation within the lattice. Discrimination between structurally incorporated and adsorbed water is enhanced by the rapid exchange of surface D(2)O with atmospheric H(2)O. Moreover, a (2)H resonance was observed for samples dried under a variety of conditions, including in vacuo heating to 150 degrees C. In contrast, a sample heated to 500 degrees C produced no deuterium resonance, indicating that structural water had been released by that temperature. We propose that water is located in the c-axis channels. Because structural water is observed even for apatites with very low carbonate content, some of the water molecules must lie between the monovalent ions. PMID- 22057815 TI - FRAX((r)) with and without bone mineral density. AB - The use of FRAX, particularly in the absence of BMD, has been the subject of some debate and is the focus of this review. The clinical risk factors used in FRAX have high validity as judged from an evidence-based assessment and identify a risk that is responsive to pharmaceutical intervention. Moreover, treatment effects, with the possible exception of alendronate, are not dependent on baseline BMD and strongly suggest that FRAX identifies high-risk patients who respond to pharmaceutical interventions. In addition, the selection of high-risk individuals with FRAX, without knowledge of BMD, preferentially selects for low BMD. The prediction of fractures with the use of clinical risk factors alone in FRAX is comparable to the use of BMD alone to predict fractures and is suitable, therefore, in the many countries where DXA facilities are sparse. In countries where access to BMD is greater, FRAX can be used without BMD in the majority of cases and BMD tests reserved for those close to a probability-based intervention threshold. Whereas the efficacy for agents to reduce fracture risk has not been tested prospectively in randomized controlled trials in patients selected on the basis of FRAX probabilities, there is compelling evidence that FRAX with or without the use of BMD provides a well-validated instrument for targeting patients most likely to benefit from an intervention. PMID- 22057816 TI - Isolated AL bundle reconstruction of the PCL. AB - INTRODUCTION: The purpose of this study was to evaluate the clinical and radiologic results after isolated reconstruction of the posterior cruciate ligament (PCL) using the semitendinosus (ST) and gracilis (GR) tendons with the arthroscopic single-bundle technique. METHODS: All patients upon whom we had performed a single-bundle PCL reconstruction between 2002 and 2005 prospectively underwent a standardized follow-up examination after 2 years. Isolated PCL reconstruction was carried out on 41 patients during the observation period. Pre- and postoperative stress radiographs were taken using the Telos stress device in order to evaluate the dorsal translation. Knee joint function and degree of activity were recorded using the Tegner activity score, the subjective International Knee Documentation Committee (IKDC) score, and the overall IKDC score. RESULTS: 33 of 41 patients (80.4%, 17 men, 16 women) completed the study. The posterior tibial translation of -10.1 +/- 1.8 mm had an overall average improvement to a postoperative value of -5.0 +/- 2.5 mm (p < 0.001). The patients showed a significant improvement in the Tegner activity score from an average 2.8 +/- 0.8 points to 5.9 +/- 1.2 points (p < 0.001). Evaluation of the subjective IKDC showed a significant improvement from a preoperative score of 41.86 +/- 11.49 points to a postoperative score of 69.54 +/- 11.39 points (p < 0.001). In total, 24 patients (72.8%) exhibited a normal or nearly normal outcome. CONCLUSION: The abovementioned reconstruction technique can achieve a stable knee function in patients with isolated PCL insufficiency. The isolated single-bundle PCL reconstruction offers an improvement regarding the activity level and stability of the knee joint. LEVEL OF EVIDENCE: Level IV. PMID- 22057817 TI - Chronic ankle instability: diagnosis and treatment. AB - BACKGROUND: Chronic ankle instability (CAI) is a very common injury but still remains an area of debate. QUESTIONS: This review aims to define the current diagnosis and treatment of persons with CAI. METHODS: A PubMed (MEDLINE) search of the years 2010 and 2011 (1 January 2010 to 15 July 2011) was performed using three keywords: ankle and chronic and instability. The number of articles in English language that was identified was 57. RESULTS: Low reliability has been found in effectively testing CAI in a clinical setting. No single force-plate measure is very effective in predicting if an individual had CAI or not. Availability of a nonradiographic device (ankle arthrometer) to measure ankle instability could improve diagnostic accuracy and facilitate decision making in patients with CAI. The sensitivity of magnetic resonance imaging (MRI) may not be adequate to detect lesions in these patients before surgery. In a symptomatic patient, negative results on MRI must be viewed with caution and an arthroscopy may still be required for a definitive diagnosis and treatment. Conservative treatment (rehabilitation, taping, brace) may reduce the occurrence of recurrent ankle sprains and may be effective in managing CAI. In patients with CAI, strengthening of the muscles around the ankle with well-planned proprioceptive exercises helped the patients return to normal living and sports activities, and prevents unnecessary surgery, especially in cases with functional instability. There is no consensus regarding optimum surgical treatment for CAI, but all of them often have good results. CONCLUSIONS: Conservative treatment of patients with CAI must be the first-line therapy. Surgical treatment must be indicated only when conservative treatment fails. PMID- 22057818 TI - Histologic examinations of arthroplasty specimens are not cost-effective: a retrospective cohort study. AB - BACKGROUND: Many hospitals require all operative specimens be sent to pathologists for routine examination. Although previous studies indicate this practice increases medical cost, it remains unclear whether it alters patient management and whether it is cost-effective. QUESTIONS/PURPOSES: We therefore (1) determined the rate of discordance between clinical and histologic examinations of routine operative specimens during elective primary arthroplasties, (2) determined the cost of routine histologic screening, and (3) estimated its cost effectiveness in terms of cost per quality-adjusted life year gained, as compared with gross examination or no examination. METHODS: We retrospectively reviewed medical records of 1247 patients who underwent 1363 routine elective primary total joint arthroplasties between January 18, 2006 and March 15, 2010. We compared preoperative, postoperative, and histologic diagnoses for each patient and categorized them into three classes: concordant (clinical and histologic diagnoses agreed), discrepant (diagnoses differed but with no resultant change in treatment), and discordant (diagnoses differed with resultant change in treatment). Medicare reimbursements were determined through the pathology department's administrative office. RESULTS: In 1363 cases, 1335 (97.9%) clinical and histologic diagnoses were concordant, 28 (2.1%) were discrepant, and none were discordant. Total reimbursement for routine pathological examination was $139,532, or $102.37 per specimen. The average cost to identify each discrepant case was $4983.29. Routine histologic examination did not alter patient management, and there was no direct gain in quality-adjusted life years. CONCLUSIONS: Our observations show routine histologic examinations of routine operative specimens during elective primary arthroplasties increase medical cost but rarely alter patient management and are not cost-effective. LEVEL OF EVIDENCE: Level I, economic and decision analyses. See Guidelines for Authors for a complete description of levels of evidence. PMID- 22057819 TI - Shared decision-making in orthopaedic surgery. AB - BACKGROUND: The process of clinical decision-making and the patient-physician relationship continue to evolve. Increasing patient involvement in clinical decision-making is embodied in the concept of "shared decision-making" (SDM), in which the patient and physician share responsibility in the clinical decision making process. Various patients' decision aid tools have been developed to enhance this process. QUESTIONS/PURPOSES: We therefore (1) describe decision making models; (2) discuss the different types of patients' decision aids available to practice SDM; and (3) describe the practice and early impact of SDM on clinical orthopaedic surgery. METHODS: We performed a search of the literature using PubMed/MEDLINE and Cochrane Library. We identified studies related to shared decision-making and the use of patients' decision aids in orthopaedics. The search resulted in 113 titles, of which 21 were included with seven studies on patients' decision aid use specifically in orthopaedics. RESULTS: Although limited studies suggest the use of patients' decision aids may enhance decision making, conclusions about the use of these aids in orthopaedic clinical practice cannot be made and further research examining the best type, timing, and content of patients' decision aids that will lead to maximum patient involvement and knowledge gains with minimal clinical workflow interruption are needed. CONCLUSION: In clinical practice today, patients are increasingly involved in clinical decision-making. Further research on SDM in orthopaedic surgery examining the feasibility and impact on practice, on patients' willingness and ability to actively participate in shared decision-making, and the timing and type of patients' decision aids appropriate for use is still needed. PMID- 22057820 TI - Nonoperative versus operative treatment for thoracolumbar burst fractures without neurologic deficit: a meta-analysis. AB - BACKGROUND: Decision-making regarding nonoperative versus operative treatment of patients with thoracolumbar burst fractures in the absence of neurologic deficits is controversial. Lack of evidence-based practice may result in patients being treated inappropriately and being exposed to unnecessary adverse consequences. PURPOSE: Using meta-analysis, we therefore compared pain (VAS) and function (Roland Morris Disability Questionnaire) in patients with thoracolumbar burst fractures without neurologic deficit treated nonoperatively and operatively. Secondary outcomes included return to work, radiographic progression of kyphosis, radiographic progression of spinal canal stenosis, complications, cost, and length of hospitalization. METHODS: We searched MEDLINE, EMBASE((r)), and the Cochrane Central Register of Controlled Trials for 'thoracic fractures', 'lumbar fractures', 'non-operative', 'operative' and 'controlled clinical trials'. We established five criteria for inclusion. Data extraction and quality assessment were in accordance with Cochrane Collaboration guidelines. The main analyses were performed on individual patient data from randomized controlled trials. Sensitivity analyses were performed on VAS pain, Roland Morris Disability Questionnaire score, kyphosis, and return to work, including data from nonrandomized controlled trials and using fixed effects meta-analysis. We identified four trials, including two randomized controlled trials consisting of 79 patients (41 with operative treatment and 38 with nonoperative treatment). The mean followups ranged from 24 to 118 months. RESULTS: We found no between-group differences in baseline pain, kyphosis, and Roland Morris Disability Questionnaire scores. At last followup, there were no between-group differences in pain, Roland Morris Disability Questionnaire scores, and return to work rates. We found an improvement in kyphosis ranging from means of 12.8o to 11o in the operative group, but surgery was associated with higher complication rates and costs. CONCLUSIONS: Operative management of thoracolumbar burst fractures without neurologic deficit may improve residual kyphosis, but does not appear to improve pain or function at an average of 4 years after injury and is associated with higher complication rates and costs. LEVEL OF EVIDENCE: Level II, therapeutic study. See the Guidelines for Authors for a complete description of level of evidence. PMID- 22057821 TI - When do patient-reported assessments peak after revision knee arthroplasty? AB - BACKGROUND: The best timing for patient visits after revision TKA is unclear. Predictors of pain and function reported in the literature typically look at the influence at a given time that might not be ideal if the score is not at a peak or the earliest possible time. Moreover, most reports of predictors include revisions for infection, which typically have a poorer outcome, or for other indications with variable outcome. QUESTIONS/PURPOSES: We therefore determined (1) the trend of recovery after revision TKA to determine the best time to measure the peak patient-reported pain and function scores and (2) the influence of comorbidities and age on the patterns of recovery. METHODS: We prospectively followed 120 patients who had revision TKAs from 2003 to 2008. The patients were assessed within 6 weeks before surgery and at 12 weeks, 1 year, and annually thereafter. We obtained WOMAC and SF-36 scores at each visit. We used a linear mixed model analysis to assess predictors. The minimum followup was 2 years (mean, 3 years; range, 2-7 years). RESULTS: The majority of improvements in the WOMAC and SF-36 scores occurred during the first year after surgery after which the scores stabilized. One of the seven independent preoperative variables studied (comorbidities) predicted a trend toward improvement of WOMAC pain, WOMAC function, and SF-36 bodily pain scores. The greater the numbers of comorbidities, the worse were the scores. Age, gender, BMI, indication for surgery, and surgeon did not independently influence the WOMAC or SF-36. CONCLUSION: Our data suggest that one of the times for patient visits after revision TKA should be 1 year after surgery. This time allows for key discrimination of implant performance. The data also confirm that patients with a greater number of comorbidities had less functional benefit from revision surgery. LEVEL OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID- 22057822 TI - Usefulness of colonoscopic examination with indigo carmine in diagnosing microscopic colitis. AB - Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is epitomized by chronic watery diarrhea, endoscopically normal colonic mucosa, and characteristic histopathological features. Reports on chromoendoscopic findings in microscopic colitis are scarce and in this paper we describe such findings. We have examined 13 patients with microscopic colitis by means of chromoendoscopy with indigo carmine 0.2 % - 0.5 %. In all 13 cases continuous mucosal changes were seen, with disappearance of innominate grooves or with irregularity of grooves. The segmental distribution of abnormal chromoendoscopic findings corresponded almost completely with the microscopic features. A diffuse mosaic pattern was found in five of 10 cases of collagenous colitis and in all three cases of lymphocytic colitis. Uneven surface was seen in four cases of collagenous colitis, one of collagenous colitis in remission, and one of lymphocytic colitis, and a nodular surface was recorded in five cases of collagenous colitis but in none of the lymphocytic colitis cases. If these findings can be reproduced in larger series of microscopic colitis cases, the need for biopsies as a diagnostic tool might be restricted to patients where chromoendoscopy shows clear mucosal changes, thereby saving costs and limiting possible complications associated with multiple biopsies. PMID- 22057823 TI - Endoscopic ultrasound-guided anterograde treatment of biliary stones following gastric bypass. AB - Endoscopic treatment of bile duct stones in gastric bypass patients is challenging. We describe a novel method involving endoscopic ultrasound (EUS) guided anterograde interventions. After prior experience with EUS-guided rendezvous endoscopic retrograde cholangiopancreatography (ERCP) and direct EUS guided anterograde stenting for malignant biliary obstruction, we have attempted EUS-guided treatment of biliary stones as first-line therapy following gastric bypass. Our approach involves: (i) EUS-fine needle aspiration (FNA) puncture into an intrahepatic bile duct; (ii) EUS-guided cholangiography; (iii) guide wire advancement across the ampulla; (iv) catheter dilation of the transhepatic transgastric access tract; (v) anterograde balloon sphincteroplasty; and (vi) anterograde advancement of stones across the ampulla using a balloon catheter. We reviewed outcomes and complications of this technique. Six patients with previous Roux-en-Y gastric bypass were referred for treatment of symptomatic choledocholithiasis. EUS-guided transhepatic puncture and cholangiography was successful in 100 %, and revealed choledocholithiasis in all patients. Tract dilation, anterograde balloon sphincteroplasty, and stone extraction were successful in four (67 %). Anterograde sphincteroplasty failed in two patients due to inability to advance the transhepatic dilation catheters. In both cases, wires were advanced down the afferent limb, and rendezvous ERCP using double balloon enteroscopy was successful. Five patients experienced no complications. One patient in whom EUS anterograde therapy failed due to difficulty in advancing the transhepatic dilation catheter, developed a subcapsular hepatic hematoma. This was managed conservatively. Direct EUS-guided treatment of biliary stones after gastric bypass appears safe and feasible. Further studies are needed to confirm the safety and efficacy of this technique. PMID- 22057824 TI - Retinal surface imaging provided by Cirrus high-definition optical coherence tomography prominently visualizes a dissociated optic nerve fiber layer appearance after macular hole surgery. AB - To investigate whether retinal surface imaging by Cirrus high-definition optical coherence tomography (HD-OCT) clearly depicts the development process of a dissociated optic nerve fiber layer (DONFL) appearance after macular hole (MH) surgery. We reviewed the medical records of the patients who underwent MH surgery with internal limiting membrane peeling. The cases were then selected using three principal criteria: (1) surgeries performed by the same surgeon (S. K.), (2) pre- and postoperative Cirrus HD-OCT imaging, and (3) minimal follow-up of 3 months. All cases received a complete ophthalmologic examination. The presence/absence of a DONFL appearance was determined using a retinal surface image provided by Cirrus HD-OCT. Color fundus photographs were also used for determination if available. Fifteen cases met the criteria. A DONFL appearance was identified in 11 (73%) cases during the postoperative course by retinal surface imaging. A DONFL appearance was not detected in any OCT retinal surface image within the first postoperative month, gradually became distinct between 1 and 3 months after surgery, and remained detectable thereafter in all cases but one whose DONFL appearance became less detectable at 12 months. Indentations of the innermost retinal layer became apparent on cross-sectional OCT images as a DONFL appearance developed on OCT retinal surface images. There were two cases in which the DONFL appearance was not observed on color fundus photographs but detected on OCT retinal surface images. Retinal surface imaging provided by Cirrus HD-OCT appeared to be a promising option in evaluating a DONFL appearance after MH surgery. PMID- 22057825 TI - Highly twisted arenes by Scholl cyclizations with unexpected regioselectivity. AB - Let's twist! The Scholl reaction with quinquephenyl derivatives has been shown to have an unexpectedly strong preference for forming twisted, helicene aromatic polycycles, instead of their flat counterparts. This tendency is so strong that it will overcome even severe steric hindrance, and the procedure can be used in the efficient synthesis of hexa-tert-butylhexabenzotriphenylene from a simple biaryl starting material (see scheme). PMID- 22057826 TI - Association of IFNGR2 gene polymorphisms with pulmonary tuberculosis among the Vietnamese. AB - Interferon-gamma (IFN-gamma) is a key molecule of T helper 1 (Th1)-immune response against tuberculosis (TB), and rare genetic defects of IFN-gamma receptors cause disseminated mycobacterial infection. The aim of the present study was to investigate whether genetic polymorphisms found in the Th1-immune response genes play a role in TB. In our study, DNA samples were collected from two series of cases including 832 patients with new smear-positive TB and 506 unrelated individuals with no history of TB in the general population of Hanoi, Vietnam. Alleles of eight microsatellite markers located around Th1-immune response-related genes and single nucleotide polymorphisms near the promising microsatellites were genotyped. A set of polymorphisms within the interferon gamma receptor 2 gene (IFNGR2) showed a significant association with protection against TB (P = 0.00054). Resistant alleles tend to be less frequently found in younger age at diagnosis (P = 0.011). Luciferase assays revealed high transcriptional activity of the promoter segment in linkage disequilibrium with resistant alleles. We conclude that the polymorphisms of IFNGR2 may confer resistance to the TB development of newly infected individuals. Contribution of the genetic factors to TB appeared to be different depending on age at diagnosis. PMID- 22057827 TI - Size effect of endohedral cluster on fullerene cage: preparation and structural studies of Y3N@C78-C2. AB - A new metallofullerene Y(3)N@C(78)-C(2) was synthesized and characterized. It was shown that Y(3)N@C(78) has an unconventional C(78)-C(2) cage with two pairs of fused pentagons closely bonded with two yttrium atoms. DFT calculations showed that the size of the ionic radii of the metals forming the caged cluster plays an important role in the non-isolated-pentagon-rule-feature of the C(78) cage. PMID- 22057828 TI - [Von Willebrand disease type 1 and pregnancy]. AB - The von Willebrand-Jurgens syndrome (VWJS) type 1 is a common hereditary bleeding disorder with a bleeding tendency located especially in the mucous membranes. Women suffering from VWJS type 1 show menorrhagia and prolonged postoperative bleedings. During pregnancy the clinical presentation varies by the increase of the von Willebrand factors. In this article the laboratory findings and the clinical presentation of patients with VWJS during pregnancy was examined. The necessity of interventions during pregnancy and at the time of delivery was under consideration. PMID- 22057829 TI - Inhaled NO and sildenafil combination in cardiac surgery patients with out-of proportion pulmonary hypertension: acute effects on postoperative gas exchange and hemodynamics. AB - BACKGROUND: The goal of this study was to examine the effects of coadministration of sildenafil and inhaled nitric oxide (iNO) in patients with out-of-proportion pulmonary hypertension who underwent cardiac valve replacement surgery. METHODS AND RESULTS: Twenty consecutive cardiac surgery patients with out-of-proportion pulmonary hypertension were randomly assigned postoperatively into 2 groups: group A received 10 ppm of iNO followed by sildenafil (100 mg) orally 30 minutes later, and group B initially received sildenafil (100 mg) orally followed by 10 ppm of iNO 60 minutes later. Hemodynamic and gas exchange data were obtained at baseline, after administration of either iNO or sildenafil alone, and at 90 minutes from baseline. In group A, iNO resulted in a significant reduction in mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance index (PVRI) (by 9.6% and 20.8%, respectively). In group B, sildenafil administration also resulted in a significant decrease in mean arterial pressure, MPAP, pulmonary artery occlusive pressure, PVRI, and systemic vascular resistance index but also in the PaO(2)/inspired fraction of oxygen ratio (by 18.7%, 22.0%, 15.7%, 31.6%, 21.3%, and 14%, respectively). In both groups, the coadministration of the 2 drugs resulted in a significant further reduction of mean arterial pressure, MPAP, pulmonary artery occlusive pressure, systemic vascular resistance index, and PVRI, whereas cardiac index and mixed venous oxygen saturation remained unchanged. The hypoxemia after sildenafil administration in group B improved after the coadministration of iNO, and thus PaO(2)/inspired fraction of oxygen returned to values near baseline. CONCLUSION: In this study, the postoperative coadministration of iNO and oral sildenafil in patients with out-of-proportion pulmonary hypertension undergoing cardiac surgery is safe and results in an additive favorable effect on pulmonary arterial pressure and pulmonary vascular resistance, without systemic hypotension and ventilation/perfusion mismatch. PMID- 22057830 TI - Involvement of N-methyl-D-aspartate receptor subunits in zinc-mediated modification of CA1 long-term potentiation in the developing hippocampus. AB - Zinc is an endogenous N-methyl-D-aspartate (NMDA) receptor blocker. It is possible that zinc-mediated modification of hippocampal CA1 long-term potentiation (LTP) is linked to the expression of NMDA receptor subunits, which varies with postnatal development. In the present study, the effect of ZnCl(2) and CaEDTA, a membrane-impermeable zinc chelator, on CA1 LTP induction was examined in hippocampal slices from immature (3-week-old) and young (6-week-old) rats. Tetanus (10-100 Hz, 1 sec)-induced CA1 LTP was more greatly enhanced in 3 week-old rats. CA1 LTP was inhibited in the presence of 2-amino-5 phosphonovalerate (APV), an NMDA receptor antagonist, and CaEDTA in 3-week-old rats, as in the case of 6-week-old rats reported previously. In 3-week-old rats, on the other hand, 5 MUM ZnCl(2) attenuated NMDA receptor-mediated EPSPs more than in 6-week-old rats and significantly attenuated CA1 LTP. Moreover, 5 MUM ZnCl(2) significantly attenuated CA1 LTP in the presence of (2R,4S)-4-(3 phosphonopropyl)-2-piperidinecarboxylic acid (PPPA), an NR2A antagonist, in 3 week-old rats, but not that in the presence of ifenprodil, an NR2B antagonist, suggesting that zinc-mediated attenuation of CA1 LTP is associated with the preferential expression of NR2B subunit in 3-week-old rats. In 6-week-old rats, however, 5 MUM ZnCl(2) significantly potentiated CA1 LTP and also CA1 LTP in the presence of PPPA. The present study demonstrates that endogenous zinc may participate in the induction of CA1 LTP. It is likely that the changes in expression of NMDA receptor subunits are involved in the zinc-mediated modification of CA1 LTP in the developing hippocampus. PMID- 22057831 TI - Cryptococcus gattii infection in an immunocompetent patient from Southern Italy. AB - Cryptococcus gattii has becoming more prevalent in temperate climate zones, during the past decades. We describe a C. gattii serotype B infection in an immunocompetent Italian patient with sclerosing cholangitis. The patient traveled once to Eastern Canada and otherwise no other countries than Italy were visited. Molecular analysis revealed that the C. gattii isolate belong to genotype AFLP4/VGI and has mating-type alpha which is the most common genotype in the Mediterranean environment. The C. gattii strain was found to be closely related, but not identical, to other C. gattii strains from the Mediterranean area. PMID- 22057833 TI - Kinetics of anaerobic elemental sulfur oxidation by ferric iron in Acidithiobacillus ferrooxidans and protein identification by comparative 2-DE MS/MS. AB - Elemental sulfur oxidation by ferric iron in Acidithiobacillus ferrooxidans was investigated. The apparent Michaelis constant for ferric iron was 18.6 mM. An absence of anaerobic ferric iron reduction ability was observed in bacteria maintained on elemental sulfur for an extended period of time. Upon transition from ferrous iron to elemental sulfur medium, the cells exhibited similar kinetic characteristics of ferric iron reduction under anaerobic conditions to those of cells that were originally maintained on ferrous iron. Nevertheless, a total loss of anaerobic ferric iron reduction ability after the sixth passage in elemental sulfur medium was demonstrated. The first proteomic screening of total cell lysates of anaerobically incubated bacteria resulted in the detection of 1599 protein spots in the master two-dimensional electrophoresis gel. A set of 59 more abundant and 49 less abundant protein spots that changed their protein abundances in an anaerobiosis-dependent manner was identified and compared to iron- and sulfur-grown cells, respectively. Proteomic analysis detected a significant increase in abundance under anoxic conditions of electron transporters, such as rusticyanin and cytochrome c(552), involved in the ferrous iron oxidation pathway. Therefore we suggest the incorporation of rus-operon encoded proteins in the anaerobic respiration pathway. Two sulfur metabolism proteins were identified, pyridine nucleotide-disulfide oxidoreductase and sulfide-quinone reductase. The important transcription regulator, ferric uptake regulation protein, was anaerobically more abundant. The anaerobic expression of several proteins involved in cell envelope formation indicated a gradual adaptation to elemental sulfur oxidation. PMID- 22057832 TI - Occurrence and toxicity of antimicrobial triclosan and by-products in the environment. AB - INTRODUCTION AND AIMS: A review was undertaken on the occurrence, toxicity, and degradation of triclosan (TCS; 5-chloro-2,4-dichlorophenoxy)phenol) in the environment. TCS is a synthetic, broad-spectrum antibacterial agent incorporated in a wide variety of household and personal care products such as hand soap, toothpaste, and deodorants but also in textile fibers used in a range of other consumer products (e.g., toys, undergarments and cutting boards among other things). OCCURRENCE: Because of its partial elimination in sewage treatment plants, most reports describe TCS as one of the most commonly encountered substances in solid and water environmental compartments. It has been detected in a microgram per liter or microgram per kilogram level in sewage treatment plants (influents, effluents, and sludges), natural waters (rivers, lakes, and estuarine waters), and sediments as well as in drinking water. TOXICITY: Moreover, due to its high hydrophobicity, TCS can accumulate in fatty tissues and has been found in fish and human samples (urine, breast milk, and serum). TCS is known to be biodegradable, photo-unstable, and reactive towards chlorine and ozone. DISCUSSION: As a consequence, it can be transformed into potentially more toxic and persistent compounds, such as chlorinated phenols and biphenyl ethers after chlorination, methyl triclosan after biological methylation, and chlorinated dibenzodioxins after photooxidation. The toxicity of TCS toward aquatic organisms like fish, crustaceans, and algae has been demonstrated with EC50 values near TCS environmental concentrations. It has even been shown to produce cytotoxic, genotoxic, and endocrine disruptor effects. CONCLUSION: Furthermore, the excessive use of TCS is suspected to increase the risk of emergence of TCS resistant bacteria and the selection of resistant strains. PMID- 22057834 TI - A geometry force field which converts low-resolution X-ray models to structures with properties found at ultra high resolution. AB - A geometry optimization force field was developed using ultra high-resolution structures and tested using high- and low-resolution X-ray structures. Protein and small molecule X-ray data was used. When applied to ultra high-resolution structures the force field conserves the internal geometry and local strain energy. When applied to low-resolution structures there is a small change in geometry accompanied by a large drop in local strain energy. Although optimization causes only small structural changes in low-resolution X-ray models, it dramatically modifies profiles for hydrogen bonding, Van der Waals contact, bonded geometry, and local strain energy, making them almost indistinguishable from those found at high resolution. Further insight into the effect of the force field was obtained by comparing geometries of homologous proteins before and after geometry optimization. Optimization causes homologous regions of structures to become similar in internal geometry and energies. Once again, the changes only require small atomic movements. These findings provide insights into the structure of molecular complexes. The new force field contains only short-range interatomic potential functions. Its effectiveness shows that local geometries are determined by short-range interactions which are well modeled by the force field. Potential applications of this study include detection of possible structural errors, correction of errors with minimal change in geometry, improved understanding and prediction of the effects of modifying ligands or proteins, and computational addition of structural water. PMID- 22057835 TI - Use of Angio-Seal closure device when the arteriotomy is above or below the common femoral artery. AB - BACKGROUND: The majority of vascular complications during diagnostic coronary angiography occur while accessing the femoral artery. Angio-Seal vascular closure devices are indicated for closure of arteriotomies of the femoral artery, but not when the puncture site is above or below the femoral artery. HYPOTHESIS: Under certain circumstances, use of the Angio-Seal closure device above or below the common femoral artery may be safe and effective. METHODS: Consecutive patients at a single high-volume medical center having documented high or low arteriotomies were closed using an Angio-Seal closure device. Patients were chosen when they received a single arterial puncture, the arteriotomy was away from branch vessels, and the diameter of the artery at the site of sheath entry was of large enough caliber to suggest placement would be successful. Patients were then followed longitudinally for complications. RESULTS: Sixty-two patients had non femoral artery sheath placement. Twenty-two patients had "high" puncture sites, and 40 patients had "low" puncture sites. All were successfully closed using the Angio-Seal vascular closure device and had no complications. CONCLUSIONS: Although not approved for placement in areas above or below the femoral artery, off-label use of the Angio-Seal arteriotomy closure may be safely performed when patient characteristics are favorable. PMID- 22057836 TI - Effect of individualized worksite exercise training on aerobic capacity and muscle strength among construction workers--a randomized controlled intervention study. AB - OBJECTIVES: The combination of high physical work demands and low physical capacity has been shown to increase the risk for cardiovascular disease and musculoskeletal disorders. The aim of this study was to assess the physical capacity of construction workers and evaluate the effect of individually tailored exercise programs on their physical fitness and muscular capacity. METHOD: The study was a randomized controlled trial of male constructions workers allocated to either an exercise or control group. The intervention lasted 12 weeks, and the exercise group trained 3 x 20 minutes a week. The participants completed health checks before and after the intervention period. Data from the first health check were used to tailor the exercise in the interventions. RESULTS: At baseline, participants had maximal oxygen consumption (VO(2max)) of 2.9 [standard deviation (SD) 0.7] l/min and body mass index (BMI) of 28.3 (SD 4.7). Compared to representative data on employees in Denmark (N=78), this study population (N=67) had significantly lower relative aerobic capacity [difference in z-score -1.13 , standard error (SE) 0.1, P<0.001] and higher BMI [difference in z-score 1.10, SE 0.2, P<0.001] at baseline. With respect to the intervention, group x time analyses showed a significant difference in estimated change in VO(2max)of 0.4 l/min for the exercise group and 0.0 l/min for the control group (P<0.001). Body mass and other general health measures remained unchanged. CONCLUSION: Training for 20 minutes, 3 times a week significantly increased VO(2max)with a clinically relevant magnitude regarding risk of cardiometabolic disorders. This study demonstrates a good effectiveness for integrating short exercise bouts into organizational routines among constructions workers. PMID- 22057837 TI - The shape of the myelosuppression time profile is related to the probability of developing neutropenic fever in patients with docetaxel-induced grade IV neutropenia. AB - PURPOSE: Chemotherapy-induced neutropenia is associated with the risk of developing febrile neutropenia (FN). The aim was to describe the time course of myelosuppression in breast cancer patients treated with docetaxel and to investigate how the shape of the predicted myelosuppression time course and earlier proposed risk factors influence the probability of developing FN. METHODS: Neutrophil counts from 140 breast cancer patients with observed grade IV neutropenia during the first course of docetaxel treatment were included. Twenty six of the patients (19%) experienced FN. The myelosuppression time course was described using a semi-mechanistic myelosuppression model in NONMEM. The individual myelosuppression model parameters [baseline neutrophil count, mean transit time (MTT) and drug effect parameter (EC(50))], myelosuppression descriptors (nadir, duration of grade IV neutropenia) and earlier suggested risk factors (age, performance status, haemoglobin and liver function) were explored to be related to FN by logistic regression. RESULTS: The neutrophil time course following docetaxel treatment was well described by the model. EC(50) and MTT were both significantly related to the probability of developing FN where low parameter values result in a rapid decline, low nadir and an increased risk of FN. None of the evaluated risk factors or myelosuppression descriptors were significant. CONCLUSION: The probability to develop FN in patients who experience grade IV neutropenia was dependent on the myelosuppression time profile. Patients with a rapid neutrophil decline and high drug sensitivity had a higher probability to develop FN. Model-based parameter estimates were superior predictors over descriptive values such as the nadir or duration of neutropenia. PMID- 22057838 TI - Treatments for relapsing-remitting multiple sclerosis: summarising current information by network meta-analysis. AB - OBJECTIVES: Oral drugs for relapsing-remitting multiple sclerosis (RRMS) have been recently investigated and, one of these, fingolimod, is already available in several countries. In this framework, an analysis of the data in terms of the comparative effectiveness for all treatments thus far approved for RRMS can be useful to reappraise their place in therapy. METHODS: After a MEDLINE search, we selected all randomised trials studying the effectiveness of drugs for RRMS and included in our analysis those randomised trials in which interferon, glatiramer, natalizumab or fingolimod were studied. The end-point was the relapse-free rate at 12 months, which was compared between the various treatments. Direct comparisons, based on actual randomised trials, were handled by calculating the trial-specific hazard ratio (HR) or the meta-analytic value of HR (when at least 2 trials were available). Indirect comparisons for which data from actual trials were missing were instead managed through a network meta-analysis. RESULTS: Ten randomised trials met the criteria set for our analysis. All active treatments were found to be significantly more effective than placebo (direct comparisons) in terms of freedom from relapse at the 12-month follow-up assessments; the values of HR ranged from 1.28 for glatiramer to 1.53 for interferon beta. The comparisons between active agents revealed that fingolimod was superior to interferon (HR = 1.18; direct comparison) and glatiramer (HR = 1.23; indirect comparison), while the other four head-to-head comparisons of treatments revealed no significant difference. CONCLUSIONS: On the basis of the effectiveness data presently available, fingolimod seems to offer the advantage of oral administration together with the most favorable profile in terms of relapse-free rate at the 1-year follow-up assessment. PMID- 22057840 TI - Advancing the paradigm for cardiovascular imaging research. PMID- 22057841 TI - Haemophilia patients with HIV- and HCV-infection. Long term survival. AB - At present (2010), we investigate in a long term study on psychosocial aspects of haemophilia at the Munich Haemophilia Centre factors which could be held responsible for the large number of still living HIV+ patients while many patients died from AIDS or from diseases caused by HCV during the 1990ies. PATIENTS, METHODS: We retrospectively compare medical and psychosocial data of 15 HIV+ long term survivors (L-S), 15 HIV+ later on deceased patients and 15 HIV-, all of them deriving from the original investigation group from 1985 including 52 patients (30 HIV+, 22 HIV-). We prove the validity of our psychosocial factors by the SF 36 which currently serves as gold standard. The actual psychosocial factors and medical parameters of the 15 L-S are checked against the data of the 15 HIV- patients. RESULTS, CONCLUSION: In 1985 already, we retrospectively found significantly higher values regarding psychosocial factors within the group of the L-S as opposed to the later on deceased ones. Highly significant are the facts that more than 90 % of HIV+ L-S have had a good relationship to their fathers and are still employed today in contrast to the deceased HIV+ patients. At present, the differences regarding psychosocial factors between HIV+ L-S and HIV-negative patients are vanishing. PMID- 22057842 TI - Aggression among children with ADHD, anxiety, or co-occurring symptoms: competing exacerbation and attenuation hypotheses. AB - Competing hypotheses for explaining the role of anxiety in the relation between attention-deficit/hyperactivity disorder (ADHD) symptoms and childhood aggression were evaluated. Two studies tested whether anxiety exacerbated, attenuated, or had no effect on the relation between ADHD and aggression subtypes among psychiatrically hospitalized children. In Study 1 (N = 99), children who scored above clinical cut-off levels for anxiety only, ADHD only, and co-occurring ADHD and anxiety were compared on aggression subtypes (i.e., reactive, proactive, overt, and relational aggression). In Study 2, the moderating role of anxiety on the relation between ADHD and aggression subtypes was examined with a larger sample (N = 265) and with continuous variables. No support was found for either the attenuation or exacerbation hypothesis, and results remained consistent when separately examining hyperactivity/impulsivity and inattention symptoms of ADHD. Although ADHD symptoms were significantly associated with all aggression subtypes, this association did not remain when including symptoms of oppositional defiant disorder. PMID- 22057843 TI - Carbon dioxide hydrogenation to formic acid by using a heterogeneous gold catalyst. AB - AUROlite, consisting of gold supported on titania (picture shows extrudates in a steel net cage), is a robust catalyst for the production of catalyst-free HCOOH/NEt(3) adducts from H(2), CO(2), and neat NEt(3). Pure HCOOH is freed from the adducts by amine exchange. PMID- 22057844 TI - Biosynthetic concepts for the production of beta-lactam antibiotics in Penicillium chrysogenum. AB - Industrial production of beta-lactam antibiotics by the filamentous fungus Penicillium chrysogenum is based on successive classical strain improvement cycles. This review summarizes our current knowledge on the results of this classical strain improvement process, and discusses avenues to improve beta lactam biosynthesis and to exploit P. chrysogenum as an industrial host for the production of other antibiotics and peptide products. Genomic and transcriptional analysis of strain lineages has led to the identification of several important alterations in high-yielding strains, including the amplification of the penicillin biosynthetic gene cluster, elevated transcription of genes involved in biosynthesis of penicillin and amino acid precursors, and genes encoding microbody proliferation factors. In recent years, successful metabolic engineering and synthetic biology approaches have resulted in the redirection of the penicillin pathway towards the production of cephalosporins. This sets a new direction in industrial antibiotics productions towards more sustainable methods for the fermentative production of unnatural antibiotics and related compounds. PMID- 22057845 TI - Roles of the N- and C-terminal sequences in Hsp27 self-association and chaperone activity. AB - The small heat shock protein 27 (Hsp27 or HSPB1) is an oligomeric molecular chaperone in vitro that is associated with several neuromuscular, neurological, and neoplastic diseases. Although aspects of Hsp27 biology are increasingly well known, understanding of the structural basis for these involvements or of the functional properties of the protein remains limited. As all 11 human small heat shock proteins (sHsps) possess an alpha-crystallin domain, their varied functional and physiological characteristics must arise from contributions of their nonconserved sequences. To evaluate the role of two such sequences in Hsp27, we have studied three Hsp27 truncation variants to assess the functional contributions of the nonconserved N- and C-terminal sequences. The N-terminal variants Delta1-14 and Delta1-24 exhibit little chaperone activity, somewhat slower but temperature-dependent subunit exchange kinetics, and temperature independent self-association with formation of smaller oligomers than wild-type Hsp27. The C-terminal truncation variants exhibit chaperone activity at 40 degrees C but none at 20 degrees C, limited subunit exchange, and temperature independent self-association with an oligomer distribution at 40 degrees C that is very similar to that of wild-type Hsp27. We conclude that more of the N terminal sequence than simply the WPDF domain is essential in the formation of larger, native-like oligomers after binding of substrate and/or in binding of Hsp27 to unfolding peptides. On the other hand, the intrinsically flexible C terminal region drives subunit exchange and thermally-induced unfolding, both of which are essential to chaperone activity at low temperature and are linked to the temperature dependence of Hsp27 self-association. PMID- 22057846 TI - Minocycline-induced reduction of brain-derived neurotrophic factor expression in relation to cancer-induced bone pain in rats. AB - Previous studies have suggested that the release of brain-derived neurotrophic factor (BDNF) from microglia in spinal cord is necessary for maintaining pain hypersensitivity after nerve injury. However, little is known about its role in cancer-induced bone pain (CIBP), which is in some ways unique. This study demonstrates a critical role of minocycline (a potent inhibitor of microglial activation)-modulated BDNF in the induction and maintenance of behavioral hypersensitivity in a rat model of CIBP. We assessed mechanical threshold and spontaneous pain of CIBP rats. Moreover, minocycline was administered intrathecally from day 4 to day 6 (early stage) or from day 10 to day 12 (later stage), after carcinoma cell inoculation. Real-time PCR, Western blots, and double immunofluorescence were used to detect the expression of OX-42 (marker of activated microglia), phosphorylated p38-MAPK (p-p38), and BDNF. We found that intrathecal minocycline could prevent CIBP at an early stage of tumor growth (from day 4 to day 6). However, at the late stage (from day 10 to day 12), intrathecal minocycline had no effect. Moreover, the expression of OX-42 and BDNF under CIBP, peaking on day 6, were all reduced after minocycline injection from day 4 to day 6. The ability of minocycline-induced reduction of BDNF in the induction of behavioral hypersensitivity could provide an opportunity for alleviating CIBP. PMID- 22057847 TI - Mating genes of the Trichophyton mentagrophytes complex. AB - The mating type (-)-specific gene of the alpha-box and the mating type (+) specific gene of the high-mobility group (HMG) DNA-binding domain were confirmed in zoophilic dematophytes of Arthroderma simii and A. vanbreuseghemii. The sequence of the alpha-box gene was 1,375 bp, containing 2 exons (from 172 to 463 bp and from 513 to 1,375 bp) in the A. simii (-) mating type strain and 1,380 bp, containing 2 exons (from 177 to 468 bp and from 518 to 1,380 bp) in the A. vanbreuseghemii (-) mating type strain. The sequence of the HMG gene was 1,871 bp, containing 2 exons (from 181 to 362 bp and from 426 to 1,440 bp, coding a protein of 398 amino acids) in the A. simii (+) mating type strain and 1,811 bp containing 2 exons (from 158 to 339 bp and from 403 to 1,381 bp, coding a protein of 386 amino acids) in the A. vanbreuseghemii (+) mating type strain. Of 15 animal isolates and 72 human isolates examined, the alpha-box gene was detected in five of the animal isolates and in none of the human isolates, while the HMG gene was detected in the other 10 of the animal isolates and in all of the human isolates. Phylogenetic analysis of the alpha-box and HMG genes of Trichophyton mentagrophytes complex strains and the Microsporum gypseum strain revealed that these strains were divided into 4 clusters; the first cluster consisting of A. vanbreuseghemii and the isolates from animals and humans, the second cluster consisting of A. simii, the third cluster consisting of A. benhamiae and the fourth cluster consisting of M. gypseum. These results indicate that anthropophilic T. mentagrophytes evolved from the A. vanbreuseghemii (+) mating strain. PMID- 22057848 TI - Identification of vimentin- and elastin-like transcripts specifically expressed in developing notochord of Atlantic salmon (Salmo salar L.). AB - The notochord functions as the midline structural element of all vertebrate embryos, and allows movement and growth at early developmental stages. Moreover, during embryonic development, notochord cells produce secreted factors that provide positional and fate information to a broad variety of cells within adjacent tissues, for instance those of the vertebrae, central nervous system and somites. Due to the large size of the embryo, the salmon notochord is useful to study as a model for exploring notochord development. To investigate factors that might be involved in notochord development, a normalized cDNA library was constructed from a mix of notochords from ~500 to ~800 day degrees . From the 1968 Sanger-sequenced transcripts, 22 genes were identified to be predominantly expressed in the notochord compared to other organs of salmon. Twelve of these genes were found to show expressional regulation around mineralization of the notochord sheath; 11 genes were up-regulated and one gene was down-regulated. Two genes were found to be specifically expressed in the notochord; these genes showed similarity to vimentin (acc. no GT297094) and elastin (acc. no GT297478). In-situ results showed that the vimentin- like transcript was expressed in both chordocytes and chordoblasts, whereas the elastin- like transcript was uniquely expressed in the chordoblasts lining the notochordal sheath. In salmon aquaculture, vertebral deformities are a common problem, and some malformations have been linked to the notochord. The expression of identified transcripts provides further insight into processes taking place in the developing notochord, prior to and during the early mineralization period. PMID- 22057850 TI - Pesticide removal from waste spray-tank water by organoclay adsorption after field application: an approach for a formulation of cyprodinil containing antifoaming/defoaming agents. AB - PURPOSE: Many reports on purification of water containing pesticides are based on studies using unformulated active ingredients. However, most commercial formulations contain additives/adjuvants or are manufactured using microencapsulation which may influence the purification process. Therefore, the main objective of this work was to develop and test a pilot scheme for decontaminating water containing pesticides formulated with antifoaming/defoaming agents. METHODS: The Freundlich adsorption coefficients of formulation of cyprodinil, a new-generation fungicide, onto the organoclay Cloisite 20A have been determined in the laboratory in order to predict the efficiency of this organoclay in removing the fungicide from waste spray-tank water. Subsequently, the adsorption tests were repeated in the pilot system in order to test the practical operation of the purification scheme. RESULTS: The laboratory adsorption tests successfully predicted the efficiency of the pilot purification system, which removed more than 96% cyprodinil over a few hours. The passing of the organoclay-cyprodinil suspension through a layer of biomass gave 100% recovery of the organoclay at the surface of the biomass after 1 week. The organoclay was composted after the treatment to try to break down the fungicide so as to allow safe disposal of the waste, but cyprodinil was not significantly dissipated after 90 days. CONCLUSION: The purification scheme proved to be efficient for decontaminating water containing cyprodinil formulated with antifoaming/defoaming agents, but additional treatments for the adsorbed residues still appear to be necessary even for a moderately persistent pesticide such as cyprodinil. Furthermore, a significant conclusion of this study concerns the high influence of pesticide formulations on the process of purification of water containing these compounds, which should be taken into account when developing innovative decontamination schemes, especially for practical applications. PMID- 22057851 TI - Optimization of ethylenediamine-grafted multiwalled carbon nanotubes for solid phase extraction of lead cations. AB - INTRODUCTION: Ethylenediamine-grafted multiwalled carbon nanotubes (MWCNTs-EDA-I and MWCNTs-EDA-II) are optimized and employed to investigate the preconcentration of lead ions (Pb(II)) in trace level. RESULTS: The results show that Pb(II) can be adsorbed quantitatively on the optimized MWCNTs in the range of pH 4-7 and MWCNTs-EDA-I has a higher maximum Pb(II) adsorption capacity (157.19 mg/g) than MWCNTs-EDA-II (89.16 mg/g). The adsorbed Pb(II) can be eluted completely using 5 mL of 1 mol/L HNO(3). DISCUSSION: A new approach using a microcolumn packed with the obtained MWCNTs-EDA-I has been developed for the preconcentration of trace amount of Pb(II). Parameters influencing the preconcentration of Pb(II), such as pH of the sample, sample volume, elution solution, and interfering ions, have been examined and optimized in detail. Under optimum experimental conditions, the limit of detection is 0.30 ng/mL with the enrichment factor of 60. The relative standard deviation (R.S.D) was 2.6% at the 20 ng/mL Pb(II) level. CONCLUSION: The method has been applied for the preconcentration of trace amount of Pb(II) in environmental water samples with satisfying results. PMID- 22057852 TI - The effect of food on the bioavailability of panobinostat, an orally active pan histone deacetylase inhibitor, in patients with advanced cancer. AB - PURPOSE: Panobinostat is a novel oral pan-deacetylase inhibitor with promising anti-cancer activity. The study aimed to determine the influence of food on the oral bioavailability of panobinostat. METHODS: This multicenter study consisted of a randomized, three-way crossover, food-effect study period (cycle 1) followed by single-agent panobinostat continual treatment phase in patients with advanced cancer. Patients received panobinostat 20 mg twice weekly, and panobinostat pharmacokinetics was investigated on days 1, 8, and 15 with a randomly assigned sequence of three prandial states (fasting, high-fat, and normal breakfast). RESULTS: Thirty-six patients were assessed for the food effect on pharmacokinetics and safety in cycle 1, after which 29 patients continued treatment, receiving single-agent panobinostat. Safety and antitumor activity were assessed during the extension period. Panobinostat systemic exposure was marginally reduced (14-16%) following food [geometric mean ratio (GMR) of the AUC(0-infinity)/high-fat breakfast/fasting, 0.84 (90% confidence interval {CI}, 0.74-0.96); normal breakfast/fasting, 0.86 (90% CI, 0.75-1.00)], and interpatient variability (coefficient of variation, 59%) remained essentially unchanged with or without food. Panobinostat C (max) was reduced by 44% (high-fat) and 36% (normal) with median T (max) prolonged by 1-1.5 h following food. Panobinostat was well tolerated, with thrombocytopenia, fatigue, nausea, and vomiting as common adverse events, and demonstrated antitumor activity with one patient with a partial response and six patients with stable disease as best response. CONCLUSIONS: Food produced minor changes in oral panobinostat exposure; thus, panobinostat can be given without regard to food intake in future clinical studies. PMID- 22057853 TI - A phase I pharmacokinetic study of bexarotene with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer (NSCLC). AB - PURPOSE: Preclinical data suggest that the synthetic retinoid bexarotene may be an effective chemopreventive agent and that it may act synergistically in combination with platinum-based chemotherapy. The primary objective of this study was to determine whether repeated doses of bexarotene capsules affect pharmacokinetic parameters of paclitaxel or carboplatin in patients with advanced non-small cell lung cancer. METHODS: Patients received treatment with paclitaxel (200 mg/m(2)) and carboplatin to provide a target AUC of 6 mg min/mL (day 1) every 3 weeks. Continuous oral bexarotene therapy (400 mg/m(2)/day) was initiated on Day 4, and patients started lipid-lowering therapy prior to beginning chemotherapy. Blood sampling to characterize the pharmacokinetic profiles of the chemotherapeutic agents with or without bexarotene was performed during cycle 1 (without concomitant bexarotene) and during cycle 2 (with concomitant bexarotene). RESULTS: An analysis of drug concentration data from 16 patients indicated that bexarotene did not affect the pharmacokinetics of paclitaxel, free carboplatin, or total carboplatin concentrations. However, both maximal plasma concentrations and total exposure of bexarotene increased by 80% in the presence of paclitaxel-carboplatin by an, as of yet, unexplained mechanism. The toxicities observed resembled those of either the chemotherapy regimen or bexarotene alone, and there was no evidence for an enhancement of any drug-related toxicity with the combined treatment. CONCLUSIONS: The administration of bexarotene, paclitaxel, and carboplatin is feasible and safe; however, the increased bexarotene plasma concentrations and exposure warrant further investigation if this combination is to be utilized clinically. PMID- 22057854 TI - A phase I pharmacokinetic study of bexarotene with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer (NSCLC). AB - PURPOSE: This is a phase I study of the retinoid X receptor agonist bexarotene (Targretin((r))) in combination with the chemotherapeutic drugs cisplatin and vinorelbine and lipid-lowering therapy. This study looked for pharmacokinetic (PK) interactions between the agents in parallel with a phase III study of the combination. METHODS: Patients (n = 26) with advanced-stage non-small-cell lung cancer received intravenous cisplatin 100 mg/m(2) on day 1 and at 4-week intervals plus intravenous vinorelbine 25 mg/m(2) weekly. Continuous oral bexarotene therapy (400 mg/m(2)/day) was initiated at day 4. Lipid-lowering therapy was initiated in all patients due to hypertriglyceridemia associated with bexarotene use. PK profiles of the chemotherapeutic agents were obtained on day 1 (without bexarotene) and during cycles 2-4 (with bexarotene). Vinorelbine (n = 18) and free cisplatin (n = 17) PK parameters in evaluable patients were determined using non-compartmental methods. RESULTS: Mean vinorelbine and free cisplatin clearance and dose-corrected AUC values with bexarotene were within 20% of respective values without concomitant bexarotene. Bexarotene levels did not vary with or without co-administration of the chemotherapeutic agents. There was no evidence of increased toxicity when bexarotene was co-administered with the chemotherapeutic agents. CONCLUSIONS: Bexarotene does not substantially affect vinorelbine or cisplatin PK, and the combination is well tolerated. The results are consistent with the mechanisms of elimination of vinorelbine (high metabolic clearance) and cisplatin (non-enzymatic and renal elimination). PMID- 22057855 TI - The effect of bexarotene on atorvastatin pharmacokinetics: results from a phase I trial of bexarotene plus chemotherapy in patients with advanced non-small cell lung cancer. AB - PURPOSE: Bexarotene (Targretin((r)) capsules) is a retinoid-X-receptor agonist and an inducer of CYP3A4-mediated metabolism. This phase I trial evaluated the pharmacokinetic (PK) and drug-drug interactions of bexarotene with chemotherapy and a lipid-lowering agent (atorvastatin or fenofibrate). This trial was run in parallel with phase III trials of the combinations to determine whether repeated doses of bexarotene capsules affect the pharmacokinetics (PK) of the chemotherapeutic or the lipid-lowering agents. METHODS: Patients (n = 48) with advanced non-small cell lung cancer were treated with repetitive cycles of either paclitaxel/carboplatin or cisplatin/vinorelbine chemotherapy, bexarotene (400 mg/m(2)/day) administered continuously starting on day 4 of chemotherapy, and a lipid-lowering drug, either atorvastatin or fenofibrate, starting at least 5 days before chemotherapy due to hypertriglyceridemia induced by bexarotene. Extensive plasma sampling to characterize the PK profiles of the lipid-lowering drugs, relevant chemotherapy agents was performed on day 1 (without bexarotene) and during chemotherapy cycles 2 or 3 (with bexarotene). RESULTS: Here, we report the drug-drug interactions between the lipid-lowering agents and bexarotene. Mean atorvastatin clearance and dose-corrected AUC values were reduced by nearly 50% with the addition of concomitant bexarotene. As fenofibrate was less effective at controlling hypertriglyceridemia, too few patients received this agent to make any meaningful conclusions about drug-drug interactions. CONCLUSIONS: A drug-drug interaction was seen in this trial with bexarotene co-administration leading to a significant reduction in the AUC of atorvastatin. The likely mechanism for this interaction is through induction of CYP3A4 by bexarotene given the role of this enzyme in the metabolism of atorvastatin. Knowledge of this interaction is important for optimizing lipid management with atorvastatin for patients receiving bexarotene. PMID- 22057856 TI - Intravascular ultrasound-guided primary percutaneous coronary intervention with drug-eluting stent implantation in patients with ST-segment elevation myocardial infarction. AB - BACKGROUND: Studies investigating the clinical outcome of intravascular ultrasound (IVUS)-guided primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) show conflicting results. The aim of our study was to evaluate whether IVUS-guidedPPCI with drug eluting stents (DESs) in STEMI patients improves clinical outcome. HYPOTHESIS: IVUS-guided PPCI is superior to angio-guided PPCI. METHODS: Three hundred forty one patients who underwent PPCI for STEMI and survived the hospitalization were enrolled in this study. Two hundred sixteen (63.3%) patients were treated with angio-guided PPCI and 125 (36.7%) patients were treated with IVUS-guided PPCI. The primary endpoint was defined as the composite of death, myocardial infarction, target vessel revascularization, and target lesion revascularization at the 3-year follow-up visit. RESULTS: Male gender, dyslipidemia, and smoking were frequent in the IVUS-guided PPCI group. These patients had a higher rate of radial approach, adjunctive ballooning, thrombectomy, and the use of a glycoprotein IIb/IIIa inhibitor. The number and length of implanted stents were higher in the IVUS-guided PPCI group. The primary end point (18.1% vs 12.8%, P = 0.22) and stent thrombosis (2.8% vs 2.4%, P = 1.00) was not different between the groups. CONCLUSIONS: In our observational study, IVUS-guided PPCI with DESs in patients with STEMI did not improve clinical outcome or stent thrombosis. PMID- 22057857 TI - Associations of mental, and medical illnesses with against medical advice discharges: the National Hospital Discharge Survey, 1988-2006. AB - This study examined the association of mental and medical illnesses with the odds for leaving against medical advice (AMA) in a national sample of adult patients who left general hospitals between 1988 and 2006. Leaving AMA was first examined as a function of year and mental illness. Multiple logistic regression analysis was then used to adjust for patient and hospital characteristics when associating mental and major medical diagnoses with AMA discharges. The results indicated that leaving AMA was most strongly associated with mental health problems. However, the impact of mental illness was attenuated after adjusting for medical illnesses, patient and hospital characteristics. The strongest predictors of AMA discharge included being self-pay, having Medicaid insurance, being young and male, and the regional location of the hospital (Northeast). When substance abuse conditions were excluded from the mental illness discharge diagnoses, mental illness had lower odds for leaving AMA. The results may be of value to clinicians, and hospital administrators in helping to profile and target patients at risk for treatment-compliance problems. Prospective primary data collection that would include patient, physician, and hospital variables is recommended. PMID- 22057858 TI - Influence of CYP2B6 516G>T polymorphism and interoccasion variability (IOV) on the population pharmacokinetics of efavirenz in HIV-infected South African children. AB - OBJECTIVE: To investigate the influence of CYP2B6 516G>T polymorphism, as a covariate, and of interoccasion variability (IOV) on the oral clearance (CL/F) of efavirenz (EFV) in treatment-naive black South African children over a period of 24 months post-antiretroviral therapy (ART) initiation. METHODS: HIV-infected black children (n = 60, aged 3-16 years), with no prior exposure to ART, eligible to commence ART and attending an outpatient clinic were enrolled into this study. Blood samples were taken at mid-dose interval at 1, 3, 6, 12, 18 and 24 months post-ART initiation. EFV plasma samples were determined with an adapted and validated LC/MS/MS method. Genotyping of the CYP2B6 G516T single nucleotide polymorphism (SNP) was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). NONMEM was used for the population pharmacokinetic modelling. RESULTS: EFV concentrations below 1 MUg/mL accounted for 18% (116/649), EFV concentrations >4 MUg/mL accounted for 29.5% (192/649) and concentrations within the therapeutic range (1-4 MUg/mL) represented 52.5% (341/649) of all the samples determined. The covariates age, weight and CYP2B6 G516Tgenotype were included in the final model with population estimates for CL/F determined as 2.46, 4.60 and 7.33 L/h for the T/T, G/T and G/G genotype groups respectively. CONCLUSIONS: The inclusion of both age and weight to predict accurate EFV CL values for the respective genotype groups within this paediatric population was required, whereas the addition of gender and body surface area did not improve the predictions. The importance of introducing IOV in a PK model for a longitudinal study with sparsely collected data was again highlighted by this investigation. PMID- 22057859 TI - Comparing satisfaction rates of Microwave and Bipolar Impedance controlled endometrial ablation. AB - PURPOSE: To compare the satisfaction rates of Microwave and Bipolar Impedance controlled endometrial ablations. METHODS: Anonymized questionnaires were sent to patients who had undergone endometrial ablations in a two and a half year period, which ended 6 months prior to the start of the study. The same questionnaires printed in pink and white sheets of paper were sent to patients who had undergone Bipolar Impedance controlled and Microwave endometrial ablations, respectively. Returned questionnaires were then analysed. RESULTS: There were no statistically significant differences in satisfaction rates of Microwave or Bipolar Impedance controlled endometrial ablations, where control of pain or menstrual bleeding was concerned. Similarly there was no difference in hysterectomy rates and the percentage of women in each group recommending the procedure to others as well as those reporting a significant improvement in quality of life after the procedure. CONCLUSIONS: Microwave endometrial ablation and Bipolar Impedance controlled endometrial ablation are both equally successful at controlling heavy menstrual bleeding with satisfaction rates around 80% for both procedures. PMID- 22057860 TI - Dynamic nuclear polarization: new methodology and applications. AB - One way to overcome the intrinsically low sensitivity of Nuclear Magnetic Resonance spectroscopy is to enhance the signal by dynamic nuclear polarization (DNP), where the polarization of high-gyromagnetic ratio (gamma) electrons is transferred to the surrounding nuclei using microwave (MW) irradiation. Recent developments in DNP instrumentations and applications have shown that DNP is one of the most effective methods to increase the nuclear spin polarization in inorganic, organic, and biological materials. It is possible to obtain a solution of molecules containing hyperpolarized nuclei in combination with methods to dissolve rapidly the polarized solid sample. In this chapter, a brief introduction on a theoretical basis and some of new DNP applications in NMR spectroscopy as well as medical applications in Magnetic Resonance Imaging (MRI) are described. PMID- 22057861 TI - Vanillin catabolism in Rhodococcus jostii RHA1. AB - Genes encoding vanillin dehydrogenase (vdh) and vanillate O-demethylase (vanAB) were identified in Rhodococcus jostii RHA1 using gene disruption and enzyme activities. During growth on vanillin or vanillate, vanA was highly upregulated while vdh was not. This study contributes to our understanding of lignin degradation by RHA1 and other actinomycetes. PMID- 22057862 TI - Live diatom silica immobilization of multimeric and redox-active enzymes. AB - Living organisms are adept in forming inorganic materials (biominerals) with unique structures and properties that exceed the capabilities of engineered materials. Biomimetic materials syntheses are being developed that aim at replicating the advantageous properties of biominerals in vitro and endow them with additional functionalities. Recently, proof-of-concept was provided for an alternative approach that allows for the production of biomineral-based functional materials in vivo. In this approach, the cellular machinery for the biosynthesis of nano-/micropatterned SiO2 (silica) structures in diatoms was genetically engineered to incorporate a monomeric, cofactor-independent ("simple") enzyme, HabB, into diatom silica. In the present work, it is demonstrated that this approach is also applicable for enzymes with "complex" activity requirements, including oligomerization, metal ions, organic redox cofactors, and posttranslational modifications. Functional expression of the enzymes beta-glucuronidase, glucose oxidase, galactose oxidase, and horseradish peroxidase in the diatom Thalassiosira pseudonana was accomplished, and 66 to 78% of the expressed enzymes were stably incorporated into the biosilica. The in vivo incorporated enzymes represent approximately 0.1% (wt/wt) of the diatom biosilica and are stabilized against denaturation and proteolytic degradation. Furthermore, it is demonstrated that the gene construct for in vivo immobilization of glucose oxidase can be utilized as the first negative selection marker for diatom genetic engineering. PMID- 22057863 TI - Disease dynamics and persistence of Musca domestica salivary gland hypertrophy virus infections in laboratory house fly (Musca domestica) populations. AB - Past surveys of feral house fly populations have shown that Musca domestica salivary gland hypertrophy virus (MdSGHV) has a worldwide distribution, with an average prevalence varying between 0.5% and 10%. How this adult-specific virus persists in nature is unknown. In the present study, experiments were conducted to examine short-term transmission efficiency and long-term persistence of symptomatic MdSGHV infections in confined house fly populations. Average rates of disease transmission from virus-infected to healthy flies in small populations of 50 or 100 flies ranged from 3% to 24% and did not vary between three tested geographical strains that originated from different continents. Introduction of an initial proportion of 40% infected flies into fly populations did not result in epizootics. Instead, long-term observations demonstrated that MdSGHV infection levels declined over time, resulting in a 10% infection rate after passing through 10 filial generations. In all experiments, induced disease rates were significantly higher in male flies than in female flies and might be explained by male-specific behaviors that increased contact with viremic flies and/or virus contaminated surfaces. PMID- 22057864 TI - Culture and molecular method for detection of Mycobacterium tuberculosis complex and Mycobacterium avium subsp. paratuberculosis in milk and dairy products. AB - A combined molecular and cultural method for the detection of the Mycobacterium tuberculosis complex (MTBC) and Mycobacterium avium subsp. paratuberculosis was developed and tested with artificially contaminated milk and dairy products. Results indicate that the method can be used for a reliable detection as a basis for first risk assessments. PMID- 22057865 TI - Rapid identification of Pseudallescheria and Scedosporium strains by using rolling circle amplification. AB - The Pseudallescheria boydii complex, comprising environmental pathogens with Scedosporium anamorphs, has recently been subdivided into five main species: Scedosporium dehoogii, S. aurantiacum, Pseudallescheria minutispora, P. apiosperma, and P. boydii, while the validity of some other taxa is being debated. Several Pseudallescheria and Scedosporium species are indicator organisms of pollution in soil and water. Scedosporium dehoogii in particular is enriched in soils contaminated by aliphatic hydrocarbons. In addition, the fungi may cause life-threatening infections involving the central nervous system in severely impaired patients. For screening purposes, rapid and economic tools for species recognition are needed. Our aim is to establish rolling circle amplification (RCA) as a screening tool for species-specific identification of Pseudallescheria and Scedosporium. With this aim, a set of padlock probes was designed on the basis of the internal transcribed spacer (ITS) region, differing by up to 13 fixed mutations. Padlock probes were unique as judged from sequence comparison by BLAST search in GenBank and in dedicated research databases at CBS (Centraalbureau voor Schimmelcultures Fungal Biodiversity Centre). RCA was applied as an in vitro tool, tested with pure DNA amplified from cultures. The species-specific padlock probes designed in this study yielded 100% specificity. The method presented here was found to be an attractive alternative to identification by restriction fragment length polymorphism (RFLP) or sequencing. The rapidity (<1 day), specificity, and low costs make RCA a promising screening tool for environmentally and clinically relevant fungi. PMID- 22057866 TI - Characterization of Streptomyces padanus JAU4234, a producer of actinomycin X2, fungichromin, and a new polyene macrolide antibiotic. AB - Strain JAU4234, identified as Streptomyces padanus, was isolated from soil collected in Jiangxi Province, China. It produced actinomycin X2, fungichromin, and a new polyene macrolide compound with antifungal activity, antifungalmycin 702. Antifungalmycin 702 had good general antifungal activity and may have potential future agricultural and/or clinical applications. PMID- 22057867 TI - Molecular survey and genetic identification of Anaplasma species in goats from central and southern China. AB - Anaplasma species are obligate intracellular rickettsial pathogens that impact the health of humans and animals. Few studies have been carried out on Anaplasma infections in central and southern China. This study was conducted to determine the coinfection rates of Anaplasma ovis, A. bovis, and A. phagocytophilum from 262 field blood samples of goats in these regions. The average prevalences of single infection of A. ovis, A. bovis, and A. phagocytophilum were 15.3, 16.0, and 6.1%, respectively. Coinfection of A. ovis and A. bovis was dominant, with an infection rate of 27.1%. Coinfection of A. ovis and A. phagocytophilum was 1.9% and that of A. bovis and A. phagocytophilum was 4.2%. Three-pathogen coinfection was found in three of four investigated provinces with a prevalence between 0 and 5.3%. The accuracy of the PCR results was corroborated by sequencing. Analysis of the 16S rRNA gene sequences of A. bovis and A. phagocytophilum confirmed the presence of these pathogens at the investigated sites and indicated the possible genetic diversity of A. phagocytophilum. Field blood inoculation of experimental animals led to successful identification and observation of the morphological shapes of A. bovis in the infected monocytes of sheep. Phylogenetic study with msp4 sequences of A. ovis indicated that the A. ovis genotypes from sheep in the north differed from the genotypes of goats in the investigated sites. PMID- 22057868 TI - Locked nucleic acid and flow cytometry-fluorescence in situ hybridization for the detection of bacterial small noncoding RNAs. AB - We describe the development and testing of a high-throughput method that enables the detection of small noncoding RNAs (ncRNAs) from single bacterial cells using locked nucleic acid probes (LNA) and flow cytometry-fluorescence in situ hybridization (flow-FISH). The LNA flow-FISH method and quantitative reverse transcription-PCR (qRT-PCR) were used to monitor the expression of three ncRNAs (6S, CsrB, and TPP-2) in Vibrio campbellii ATCC BAA-1116 cultures during lag phase, mid-log phase, and stationary phase. Both LNA flow-FISH and qRT-PCR revealed that CsrB and TPP-2 were highly expressed during lag phase but markedly reduced in mid-log phase and stationary phase, whereas 6S demonstrated no to little expression during lag phase but increased thereafter. Importantly, while LNA flow-FISH and qRT-PCR demonstrated similar overall expression trends, only LNA flow-FISH, which enabled the detection of ncRNAs in individual cells as opposed to the lysate-based ensemble measurements generated by qRT-PCR, was able to capture the cell-to-cell heterogeneity in ncRNA expression. As such, this study demonstrates a new method that simultaneously enables the in situ detection of ncRNAs and the determination of gene expression heterogeneity within an isogenic bacterial population. PMID- 22057869 TI - Factors influencing the microbial composition of metalworking fluids and potential implications for machine operator's lung. AB - Hypersensitivity pneumonitis, also known as "machine operator's lung" (MOL), has been related to microorganisms growing in metalworking fluids (MWFs), especially Mycobacterium immunogenum. We aimed to (i) describe the microbiological contamination of MWFs and (ii) look for chemical, physical, and environmental parameters associated with variations in microbiological profiles. We microbiologically analyzed 180 MWF samples from nonautomotive plants (e.g., screw machining or metal-cutting plants) in the Franche-Comte region in eastern France and 165 samples from three French automotive plants in which cases of MOL had been proven. Our results revealed two types of microbial biomes: the first was from the nonautomotive industry, showed predominantly Gram-negative rods (GNR), and was associated with a low risk of MOL, and the second came from the automotive industry that was affected by cases of MOL and showed predominantly Gram-positive rods (GPR). Traces of M. immunogenum were sporadically detected in the first type, while it was highly prevalent in the automotive sector, with up to 38% of samples testing positive. The use of chromium, nickel, or iron was associated with growth of Gram-negative rods; conversely, growth of Gram-positive rods was associated with the absence of these metals. Synthetic MWFs were more frequently sterile than emulsions. Vegetable oil-based emulsions were associated with GNR, while mineral ones were associated with GPR. Our results suggest that metal types and the nature of MWF play a part in MWF contamination, and this work shall be followed by further in vitro simulation experiments on the kinetics of microbial populations, focusing on the phenomena of inhibition and synergy. PMID- 22057870 TI - Association of constitutive hyperphosphorylation of Hsf1p with a defective ethanol stress response in Saccharomyces cerevisiae sake yeast strains. AB - Modern sake yeast strains, which produce high concentrations of ethanol, are unexpectedly sensitive to environmental stress during sake brewing. To reveal the underlying mechanism, we investigated a well-characterized yeast stress response mediated by a heat shock element (HSE) and heat shock transcription factor Hsf1p in Saccharomyces cerevisiae sake yeast. The HSE-lacZ activity of sake yeast during sake fermentation and under acute ethanol stress was severely impaired compared to that of laboratory yeast. Moreover, the Hsf1p of modern sake yeast was highly and constitutively hyperphosphorylated, irrespective of the extracellular stress. Since HSF1 allele replacement did not significantly affect the HSE-mediated ethanol stress response or Hsf1p phosphorylation patterns in either sake or laboratory yeast, the regulatory machinery of Hsf1p is presumed to function differently between these types of yeast. To identify phosphatases whose loss affected the control of Hsf1p, we screened a series of phosphatase gene deletion mutants in a laboratory strain background. Among the 29 mutants, a Deltappt1 mutant exhibited constitutive hyperphosphorylation of Hsf1p, similarly to the modern sake yeast strains, which lack the entire PPT1 gene locus. We confirmed that the expression of laboratory yeast-derived functional PPT1 recovered the HSE-mediated stress response of sake yeast. In addition, deletion of PPT1 in laboratory yeast resulted in enhanced fermentation ability. Taken together, these data demonstrate that hyperphosphorylation of Hsf1p caused by loss of the PPT1 gene at least partly accounts for the defective stress response and high ethanol productivity of modern sake yeast strains. PMID- 22057871 TI - New approaches for isolation of previously uncultivated oral bacteria. AB - A significant number of microorganisms from the human oral cavity remain uncultivated. This is a major impediment to the study of human health since some of the uncultivated species may be involved in a variety of systemic diseases. We used a range of innovations previously developed to cultivate microorganisms from the human oral cavity, focusing on anaerobic species. These innovations include (i) in vivo cultivation to specifically enrich for species actively growing in the oral cavity (the "minitrap" method), (ii) single-cell long-term cultivation to minimize the effect of fast-growing microorganisms, and (iii) modifications of conventional enrichment techniques, using media that did not contain sugar, including glucose. To enable cultivation of obligate anaerobes, we maintained strict anaerobic conditions in most of our cultivation experiments. We report that, on a per cell basis, the most successful recovery was achieved using minitrap enrichment (11%), followed by single-cell cultivation (3%) and conventional plating (1%). Taxonomically, the richest collection was obtained using the single-cell cultivation method, followed by minitrap and conventional enrichment, comprising representatives of 13, 9, and 4 genera, respectively. Interestingly, no single species was isolated by all three methods, indicating method complementarity. An important result is the isolation and maintenance in pure culture of 10 strains previously only known by their molecular signatures, as well as representatives of what are likely to be three new microbial genera. We conclude that the ensemble of new methods we introduced will likely help close the gap between cultivated and uncultivated species from the human oral cavity. PMID- 22057872 TI - The effects of leflunomide on CD4(+)CD25 (+)Foxp3 (+) T regulatory cells in mice receiving allogeneic bone marrow transplantation. AB - OBJECTIVE AND DESIGN: Leflunomide (LEF) is effective not only in different animal models of autoimmune diseases and the therapy of patients with rheumatoid arthritisbut also in graft rejection. The effect of LEF on CD4(+)CD25(+)T regulatory cells (Treg) was determined in a mouse model of allogeneic bone marrow transplantation. MATERIAL OR SUBJECTS: BALB/c and C57BL/6 mice were used as donors and recipients, respectively. TREATMENT: C57BL/6 mice were given 2 Gy total-body irradiation, followed by an intravenous injection of 2 * 10(7) BALB/c bone marrow cells (BMCs). Mice were treated with LEF daily at a dose of 30 mg/kg/day for 2 weeks. RESULTS: In naive mice, LEF significantly decreased the percentage of CD4(+)CD25(+) Treg cells in spleens (P < 0.05), but not in lymph nodes, though LEF enhanced the percentages of CD4(+)CD25(+) Treg cells in CD4 single positive cells in the thymocytes and blood (P < 0.05). Furthermore, LEF significantly decreased the percentage of CD4(+)CD25(+) Treg cells in the spleens of mice that received allogeneic BMCs. CONCLUSIONS: LEF decreases peripheral CD4(+)CD25(+) Treg cells in un-immunizing and immunizing recipients, indicating that LEF might not be an ideal candidate for the treatment of autoimmune diseases or graft rejection with respect to induction of immune tolerance. PMID- 22057873 TI - Nanomedicine: evolutionary and revolutionary developments in the treatment of certain inflammatory diseases. AB - Nanomedicine, although in a nascent stage of development at present, is already a reality. Several pharmaceutical products using this modern technology are already on the market. Nanotechnology offers many potential benefits to medical research. Nanoparticle-based drug carriers can increase the efficacy and safety of drugs by enhancing capacity, improving solubility, combining multiple drugs, protecting against metabolism, and controlling release. Nanoparticles can also form the basis of multifunctional drug delivery vehicles by combining targeting, imaging, and therapeutic moieties. Multifunctional nanoparticles have tremendous potential to treat human diseases. The use of non-viral carriers (nanoparticles) can also improve the cellular/nuclear uptake of corresponding nucleotides. Preclinical characterization of nanoparticles intended for medical applications is complicated-due to the variety of materials used, their unique surface properties, and multifunctional nature. It is hard to predict what precise course nanomedicine will take in years to come. It is, however, very likely that this relatively young research area will become a driving force behind a vast revolution in medical treatment. PMID- 22057874 TI - The Flex-TipTM tracheal tube does not reduce the incidence of postoperative sore throat: a randomized controlled trial. AB - PURPOSE: Sore throat after tracheal intubation is common with an incidence of 30 70%. The Parker Flex-TipTM endotracheal tube (ETT) is designed to reduce trauma during ETT placement. This randomized single-blinded trial was designed to assess whether using the Flex-Tip ETT would reduce the incidence of postoperative sore throat and/or vocal change. METHODS: A Flex-Tip or a Mallinckrodt Hi-Lo(r) cuffed ETT was used by random allocation in 200 patients with normal-appearing airways requiring elective orotracheal intubation. On the second postoperative day, a blinded assessor recorded the incidence and severity of postoperative sore throat and voice alteration. The primary outcome was the incidence of moderate or severe sore throat. Secondary outcomes included vocal change, time to intubation, number of attempts/failures, incidence of oropharyngeal bleeding, and subjective ease of intubation. RESULTS: Demographic data were similar between the two groups. Moderate or severe sore throat was observed in 12% of patients with the Flex-Tip ETT and 6% of patients with the Mallinckrodt Hi-Lo ETT (odds ratio [OR] 2.1; 95% confidence intervals [CI] 0.70 to 7.1; P = 0.14). The incidence of moderate or severe vocal change was 6% and 3%, respectively (OR 2.0; 95% CI 0.42 to 12.9; P = 0.50). Time to intubation, number of intubation attempts, incidence of oropharyngeal bleeding, and ease of intubation did not differ significantly between groups. CONCLUSION: In this study involving experienced clinicians, no significant difference was observed in the incidence of postoperative sore throat or vocal change between the Flex-Tip ETT and the standard Mallinckrodt Hi-Lo cuffed ETT. This trial was registered at www.clinicaltrials.gov , NCT01095861. PMID- 22057875 TI - Remifentanil versus fentanyl for intravenous patient-controlled labour analgesia: an observational study. AB - PURPOSE: We undertook a retrospective study to compare the analgesic efficacy and effects on neonatal outcome of administering either remifentanil or fentanyl intravenous patient-controlled analgesia (IVPCA) during labour. METHODS: A five year retrospective cohort study was undertaken of women with more than 24 weeks of gestation who had received either IVPCA remifentanil or fentanyl for labour analgesia at Mount Sinai Hospital. The sampling timeframe was from November 2005 to March 2010. The standard IVPCA regimen for the remifentanil group consisted of a PCA bolus 0.25 MUg.kg(-1) with a lockout interval of two minutes, a four-hour limit of 3 mg, and a background infusion of 0.025-0.05 MUg.kg(-1).min(-1), whereas the standard IVPCA regimen for the fentanyl group consisted of a PCA bolus 25-50 MUg with a lockout interval of three to six minutes and a four-hour limit of 1-1.5 mg. The following data were compared: maternal hourly pain scores (verbal pain score scale 0-10), sedation scores (scale 0-3), adverse effects, and neonatal outcomes. Mixed linear modelling was used to analyze longitudinal data on pain scores over time. The exact Wilcoxon test and the Fisher's exact test were used for other comparisons. RESULTS: Ninety-eight women were studied. There was no significant difference in the model-adjusted pain scores between the two groups (P = 0.86). There was a moderate decrease in pain scores in both groups compared with the baseline values. There was no difference in maternal side effects between the two groups, although transient oxygen desaturation was observed more frequently in the remifentanil group than in the fentanyl group (13% vs 2%, respectively; odds ratio, 7.32; 95% confidence interval [CI], 0.85 to 63.3). A larger number of neonates in the fentanyl group required resuscitation compared with neonates in the remifentanil group (59% vs 25%, respectively; odds ratio, 4.33; 95% CI, 1.75 to 10.76); adjusted (44% vs 8%, respectively; odds ratio, 8.56; 95% CI, 2.17 to 33.77). CONCLUSIONS: Intravenous patient-controlled analgesia with either remifentanil or fentanyl provides a moderate degree of labour analgesia, whereas transient maternal oxygen desaturation is observed more commonly with remifentanil. Fentanyl is associated with a higher need for neonatal resuscitation. PMID- 22057876 TI - Markers of plaque instability in the early diagnosis and risk stratification of acute myocardial infarction. AB - BACKGROUND: Plaque erosion and plaque rupture occur early in the pathophysiology of acute myocardial infarction (AMI). We hypothesized that markers of plaque instability might be useful in the early diagnosis and risk stratification of AMI. METHODS: In this multicenter study, we examined 4 markers of plaque instability, myeloperoxidase (MPO), myeloid-related protein 8/14 (MRP-8/14), pregnancy-associated plasma protein-A (PAPP-A), and C-reactive protein (CRP) in 398 consecutive patients presenting to the emergency department with acute chest pain and compared them to normal and high-sensitivity cardiac troponin T (cTnT and hs-cTnT). The final diagnosis was adjudicated by 2 independent cardiologists. Primary prognostic end point was death during a median follow-up of 27 months. RESULTS: The adjudicated final diagnosis was AMI in 76 patients (19%). At emergency department presentation, concentrations of all 4 biomarkers of plaque instability were significantly higher in patients with AMI than in patients with other diagnoses. However, their diagnostic accuracy as quantified by the area under the ROC curve (AUC) was low (MPO 0.63, MRP-8/14 0.65, PAPP-A 0.62, CRP 0.59) and inferior to both normal and high-sensitivity cardiac troponin T (cTnT 0.88, hs-cTnT 0.96; P<0.001 for all comparisons). Thirty-nine patients (10%) died during follow-up. Concentrations of MPO, MRP-8/14, and CRP were higher in nonsurvivors than in survivors and predicted all-cause mortality with moderate accuracy. CONCLUSIONS: Biomarkers of plaque instability do not seem helpful in the early diagnosis of AMI but may provide some incremental value in the risk stratification of patients with acute chest pain. PMID- 22057877 TI - Therapy refractory menorrhagia as first manifestation of Hermansky-Pudlak syndrome. AB - INTRODUCTION: Oculocutaneous albinism (OCA) in combination with a platelet function defect caused by a disturbed release reaction from platelet delta granules (storage pool defect - SPD) is typical for the autosomal recessive inherited Hermansky-Pudlak syndrome (HPS). CASE REPORT: A girl (age: 13 years) with OCA was hospitalized with transfusion-requiring menorrhagia. The suspicion of HPS was confirmed by results of lumi-aggregometry. Suspecting a disorder in primary haemostasis treatment with tranexamic acid (10 mg/kg body weight every 8 h i. v.), desmopressin (0.3 ug/kg body weight every 8 to 12 h) and hormonal therapy (norethisterone) was started but the menorrhagia persisted. Clinical response was finally achieved by a single injection of 100 ug/kg body weight recombinant factor VIIa (rFVIIa). CONCLUSION: The diagnosis of HPS should be suspected in patients with OCA and bleeding symptoms and is confirmed by the proof of SPD. In case of absent clinical response to desmopressin the application of rFVIIa should be considered. Hormones and antifibrinolytics are useful options in the treatment of extensive menorrhagia. PMID- 22057878 TI - Biosynthesis of lactate-containing polyesters by metabolically engineered bacteria. AB - Due to increasing concerns about environmental problems, climate change and limited fossil resources, bio-based production of chemicals and polymers is gaining attention as one of the solutions to these problems. Polyhydroxyalkanoates (PHAs) are polyesters that can be produced by microbial fermentation. PHAs are synthesized using monomer precursors provided from diverse metabolic pathways and are accumulated as distinct granules inside the cells. On the other hand, most so-called bio-based polymers including polybutylene succinate, polytrimethylene terephthalate, and polylactic acid (PLA) are synthesized by a chemical process using monomers produced by fermentation. PLA, an attractive biomass-derived plastic, is currently synthesized by heavy metal catalyzed ring opening polymerization of L-lactide that is made from fermentation derived L-lactic acid. Recently, a complete biological process for the production of PLA and PLA copolymers from renewable resources has been developed by direct fermentation of recombinant bacteria employing PHA biosynthetic pathways coupled with a novel metabolic pathway. This could be accomplished by establishing a pathway for generating lactyl-CoA and engineering PHA synthase to accept lactyl CoA as a substrate combined with systems metabolic engineering. In this article, we review recent advances in the production of lactate-containing homo- and co polyesters. Challenges remaining to efficiently produce PLA and its copolymers and strategies to overcome these challenges through metabolic engineering combined with enzyme engineering are discussed. PMID- 22057879 TI - Practitioner's guide to assessment of autism spectrum disorders in infants and toddlers. AB - Recent advances in clinical research have made it possible to diagnosis autism spectrum disorders (ASD) as early as the second year of life. The diagnostic process early in development is often complex, and thus, familiarity with the most recent findings in clinical assessment instruments, early symptoms, and developmental trajectories of young children with autism is essential. This paper provides an empirically based practitioner's guide to issues and concerns related to early diagnosis of ASD in very young children, documentation of the course and patterns of ASD symptomatology in infants and toddlers, and current understanding in the field of diagnostic outcomes of children identified in the first and second year of life. PMID- 22057880 TI - Nitrile alkylations through sulfinyl-metal exchange. PMID- 22057888 TI - Transplant-mediated repair properties of rat olfactory mucosal OM-I and OM-II sphere-forming cells. AB - Olfactory mucosa is a source of cells for transplant-mediated repair of spinal cord injury (SCI) and is currently being assessed in clinical trials. We previously reported that olfactory mucosa can generate two types of sphere forming cells with stem cell-like properties. Here we have assessed the repair potential of these cells in a rodent SCI model. Sphere-forming cells transplanted into a dorsal column injury integrated with the host spinal cord, filling the injury cavity, but showed no evidence of differentiation in vivo. Moreover, transplants supported robust axonal regeneration, particularly when suspensions of smaller spheres, rather than large aggregates, were transplanted. However, tract-tracing of dorsal column fibers showed that regenerating axons did not extend beyond the transplant. These observations show that undifferentiated olfactory spheres, though capable of supporting axonal regeneration, do not show any advantage over olfactory ensheathing cells isolated from adult olfactory tissue. In addition, olfactory spheres induced a greater astrocytic hypertrophy at the injury site than previously observed for purified olfactory ensheathing cells. PMID- 22057887 TI - Innate and adaptive immune responses against Staphylococcus aureus skin infections. AB - Staphylococcus aureus is an important human pathogen that is responsible for the vast majority of bacterial skin and soft tissue infections in humans. S. aureus can also become more invasive and cause life-threatening infections such as bacteremia, pneumonia, abscesses of various organs, meningitis, osteomyelitis, endocarditis, and sepsis. These infections represent a major public health threat due to the enormous numbers of these infections and the widespread emergence of methicillin-resistant S. aureus (MRSA) strains. MSRA is endemic in hospitals worldwide and is rapidly spreading throughout the normal human population in the community. The increasing frequency of MRSA infections has complicated treatment as these strains are more virulent and are increasingly becoming resistant to multiple different classes of antibiotics. The important role of the immune response against S. aureus infections cannot be overemphasized as humans with certain genetic and acquired immunodeficiency disorders are at an increased risk for infection. Understanding the cutaneous immune responses against S. aureus is essential as most of these infections occur or originate from a site of infection or colonization of the skin and mucosa. This review will summarize the innate immune responses against S. aureus skin infections, including antimicrobial peptides that have direct antimicrobial activity against S. aureus as well as pattern recognition receptors and proinflammatory cytokines that promote neutrophil abscess formation in the skin, which is required for bacterial clearance. Finally, we will discuss the recent discoveries involving IL-17 mediated responses, which provide a key link between cutaneous innate and adaptive immune responses against S. aureus skin infections. PMID- 22057889 TI - hRpn13, a newly identified component of the 19S particle, regulates proliferation, differentiation, and function in the human osteoblast-like cell line MG63. [corrected]. AB - The 26S proteasome is a key component of the ubiquitin-proteasome system, a process responsible for the majority of cellular protein degradation. The function of the proteasomal ubiquitin receptor hRpn13, a component of the 26S proteasome, is not completely understood. To investigate the role of hRpn13 in the ubiquitin-proteasome system in osteoblasts, the effects of suppressing and overexpressing the hRpn13 gene on proliferation, differentiation, and function of human osteoblast-like MG63 cells were examined. After knockdown of hRpn13 by small interfering RNA, changes in osteoblast proliferation were evaluated by methyl-thiazolyl-tetrazolium assay. There was an increase in markers for osteoblast proliferation, specifically alkaline phosphatase activity, and elevated protein levels of osteocalcin, proliferating cell nuclear antigen (PCNA), and ubiquitin. Furthermore, hRpn13 knockdown also resulted in a decrease in the ratio between the gene expressions of RANKL and OPG, key players in the pathogenesis of bone diseases that influence the normal balance between bone formation and resorption. In contrast, overexpression of hRpn13 inhibited the proliferation of MG63 cells, and decreased alkaline phosphatase activity as well as protein levels of osteocalcin, PCNA, and ubiquitin while the ratio of RANKL to OPG expression increased. To confirm the function of hRpn13 in the ubiquitin proteasome pathway, osteoblast proliferation enhancement and ubiquitin accumulation after hRpn2 knockdown was assessed. The results suggest that overexpression of hRpn13 negatively influences proliferation and osteogenic differentiation in MG63 cells. The evidence implies that hRpn13 modulates the influence of osteoblasts on osteoclasts by controlling the stability of regulatory proteins in osteoblasts. In summary, overexpression of hRpn13 promoted the activity of the ubiquitin-proteasome system. PMID- 22057890 TI - Giant cell tumour of the ovary in a 70-year-old nulliparous woman: a case report and review of literature. PMID- 22057891 TI - The investigation of ABO and Rh blood groups distribution in patients with endometriosis needs new project design. AB - We carefully studied all the three published papers in your journal as "ABO and Rh Blood group distribution in patients with endometriosis" and "Associations of ABO blood groups with various gynecologic diseases" and would like to express our point of view about them. PMID- 22057892 TI - Impact of prior bariatric surgery on maternal and fetal outcomes among obese and non-obese mothers. AB - PURPOSE: To assess the association between bariatric surgery and pregnancy related outcomes among obese and non-obese women in the state of Florida. METHODS: We conducted a population-based, retrospective cohort analysis using vital records and hospital discharge data in Florida during 2004-2007. Women were categorized based on prior bariatric surgery and pre-pregnancy obesity status. Maternal complications (i.e., anemia, pre-eclampsia, gestational diabetes, chronic hypertension, endocrine disorders, cesarean section, prolonged hospital stay) and fetal morbidities [macrosomia, preterm birth, small for gestational age (SGA)] were the outcomes of interest. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) were computed. RESULTS: Mothers with a prior history of bariatric surgery, regardless of obesity status, were more likely to have anemia, chronic hypertension, endocrine disorders, and SGA infants. Classification based on prior history of bariatric surgery and obesity status showed that non-obese mothers with prior bariatric surgery were more likely to have anemia, chronic hypertension, endocrine disorders, and SGA infants, whereas obese mothers without prior bariatric surgery were at greater risk of having gestational diabetes, chronic hypertension, macrosomic infants (AOR = 1.69, 95% CI = 1.65-1.73), and prolonged hospital stay as compared to non-obese mother without prior bariatric surgery. CONCLUSIONS: Although prior bariatric surgery is associated with multiple negative maternal and fetal outcomes, it is protective against infant macrosomia in obese mothers. Our findings support the need for preconception/interconception services tailored for former bariatric surgery patients to improve maternal and feto-infant health outcomes. PMID- 22057893 TI - A conserved interaction with the chromophore of fluorescent proteins. AB - The chromophore of fluorescent proteins, including the green fluorescent protein (GFP), contains a highly conjugated imidazolidinone ring. In many fluorescent proteins, the carbonyl group of the imidazolidinone ring engages in a hydrogen bond with the side chain of an arginine residue. Prior studies have indicated that such an electrophilic carbonyl group in a protein often accepts electron density from a main-chain oxygen. A survey of high-resolution structures of fluorescent proteins indicates that electron lone pairs of a main-chain oxygen Thr62 in GFP-donate electron density into an antibonding orbital of the imidazolidinone carbonyl group. This n->pi* electron delocalization prevents structural distortion during chromophore excitation that could otherwise lead to fluorescence quenching. In addition, this interaction is present in on-pathway intermediates leading to the chromophore, and thus could direct its biogenesis. Accordingly, this n->pi* interaction merits inclusion in computational and photophysical analyses of the chromophore, and in speculations about the molecular evolution of fluorescent proteins. PMID- 22057894 TI - Managing emissions of active pharmaceutical ingredients from manufacturing facilities: an environmental quality standard approach. AB - Active pharmaceutical ingredient (API) residues have been found to be widespread in the aquatic environment, albeit in most cases at trace levels, with the route to the environment predominantly being via therapeutic use and subsequent excretion to sewer. Although manufacturing discharges may be a low overall contributor to environmental concentrations, they need to be managed effectively so that they do not adversely affect the local receiving environment. In order to achieve this, a risk-based approach is proposed that identifies the long-term and short-term concentrations, referred to as environmental reference concentrations (ERCs) and maximum tolerable concentrations (MTCs), respectively, of an API which should not be exceeded in the aquatic environment receiving effluent from pharmaceutical manufacturing sites. The ERC approach is based on established environmental quality standard concepts currently used in much national and international legislation. Building on these concepts, the approach takes into account indirect exposure of potential consumers such as fish-eating mammals and humans, as well as primary producers (e.g., algae) and primary and secondary consumers (e.g., invertebrates and fish). Although chronic toxicity data are preferred for ERC derivation, acute data, with appropriate considerations of uncertainty, may be used when chronic data are not available. This approach takes all available information into account, particularly for older established medicines that may predate current regulatory requirements for environmental data, and consequently helps prioritize resources for environmental testing. The ERC approach has been applied to 30 of AstraZeneca's APIs. Merits of the approach are discussed together with opportunities for potential future refinement. PMID- 22057895 TI - Glial molecular alterations with mouse brain development and aging: up-regulation of the Kir4.1 and aquaporin-4. AB - Glial cells, besides participating as passive supporting matrix, are also proposed to be involved in the optimization of the interstitial space for synaptic transmission by tight control of ionic and water homeostasis. In adult mouse brain, inwardly rectifying K+ (Kir4.1) and aquaporin-4 (AQP4) channels localize to astroglial endfeets in contact with brain microvessels and glutamate synapses, optimizing clearance of extracellular K(+) and water from the synaptic layers. However, it is still unclear whether there is an age-dependent difference in the expressions of Kir4.1 and AQP4 channels specifically during postnatal development and aging when various marked changes occur in brain and if these changes region specific. RT-PCR and immunoblotting was conducted to compare the relative expression of Kir4.1 and AQP4 mRNA and protein in the early and mature postnatal (0-, 15-, 45-day), adult (20-week), and old age (70-week) mice cerebral and cerebellar cortices. Expressions of Kir4.1 and AQP4 mRNA and protein are very low at 0-day. A pronounced and continuous increase was observed by mature postnatal ages (15-, 45-days). However, in the 70-week-old mice, expressions are significantly up-regulated as compared to 20-week-old mice. Both genes follow the same age-related pattern in both cerebral and cerebellar cortices. The time course and expression pattern suggests that Kir4.1 and AQP4 channels may play an important role in brain K(+) and water homeostasis in early postnatal weeks after birth and during aging. PMID- 22057896 TI - Postprandial antioxidant gene expression is modified by Mediterranean diet supplemented with coenzyme Q(10) in elderly men and women. AB - Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial gene expression and protein levels involved in oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) improves this situation in an elderly population. Twenty participants were randomized to receive three isocaloric diets each for 4 weeks: Mediterranean diet supplemented with CoQ (Med + CoQ diet), Mediterranean diet (Med diet), saturated fatty acid rich diet (SFA diet). After 12-h fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Nrf2, p22(phox) and p47(phox), superoxide dismutase 1 and 2 (SOD1 and SOD2), glutathione peroxidase 1 (GPx1), thiorredoxin reductase (TrxR) gene expression and Kelch-like ECH associating protein 1 (Keap-1) and citoplasmic and nuclear Nrf2 protein levels were determined. Med and Med + CoQ diets induced lower Nrf2, p22(phox), p47(phox), SOD1, SOD2 and TrxR gene expression and higher cytoplasmic Nrf2 and Keap-1 protein levels compared to the SFA diet. Moreover, Med + CoQ diet produced lower postprandial Nrf2 gene expression and lower nuclear Nrf2 protein levels compared to the other diets and lower GPx1 gene expression than the SFA diet. Our results support the antioxidant effect of a Med diet and that exogenous CoQ supplementation has a protective effects against free radical overgeneration through the lowering of postprandial oxidative stress modifying the postprandial antioxidant protein levels and reducing the postprandial expression of antioxidant genes in peripheral blood mononuclear cells. PMID- 22057897 TI - Insulin receptor signaling mediates APP processing and beta-amyloid accumulation without altering survival in a transgenic mouse model of Alzheimer's disease. AB - In brains from patients with Alzheimer's disease (AD), expression of insulin receptor (IR), insulin-like growth factor-1 receptor (IGF-1R), and insulin receptor substrate proteins is downregulated. A key step in the pathogenesis of AD is the accumulation of amyloid precursor protein (APP) cleavage products, beta amyloid (Abeta)(1-42) and Abeta(1-40). Recently, we and others have shown that central IGF-1 resistance reduces Abeta accumulation as well as Abeta toxicity and promotes survival. To define the role of IR in this context, we crossed neuron specific IR knockout mice (nIR(-/-)) with Tg2576 mice, a well-established mouse model of an AD-like pathology. Here, we show that neuronal IR deficiency in Tg2576 (nIR(-/-)Tg2576) mice leads to markedly decreased Abeta burden but does not rescue premature mortality of Tg2576 mice. Analyzing APP C-terminal fragments (CTF) revealed decreased alpha-/beta-CTFs in the brains of nIR(-/-)Tg2576 mice suggesting decreased APP processing. Cell based experiments showed that inhibition of the PI3-kinase pathway suppresses endosomal APP cleavage and decreases alpha- as well as beta-secretase activity. Deletion of only one copy of the neuronal IGF-1R partially rescues the premature mortality of Tg2576 mice without altering total amyloid load. Analysis of Tg2576 mice expressing either a dominant negative or constitutively active form of forkhead box-O (FoxO)1 did not reveal any alteration of amyloid burden, APP processing and did not rescue premature mortality in these mice. Thus, our findings identified IR signaling as a potent regulator of Abeta accumulation in vivo. But exclusively decreased IGF 1R expression reduces AD-associated mortality independent of beta-amyloid accumulation and FoxO1-mediated transcription. PMID- 22057898 TI - Protein storage and root:shoot reallocation provide tolerance to damage in a hybrid willow system. AB - To determine the mechanistic basis of tolerance, we evaluated six candidate traits for tolerance to damage using F(2) interspecific hybrids in a willow hybrid system. A distinction was made between reproductive tolerance and biomass tolerance; reproductive tolerance was designated as a plant's proportional change in catkin production following damage, while biomass tolerance referred to a plant's proportional change in biomass (i.e., regrowth) following damage. F(2) hybrids were generated to increase variation and independence among candidate traits. Using three clonally identical individuals, pre-damage candidate traits for tolerance to damage (root:shoot ratio, total nonstructural carbohydrate, and total available protein) and post-damage candidate traits (relative root:shoot ratio, phenolic ratio, and specific leaf area ratio) were measured. The range of variation for these six candidate traits was broad. Biomass was significantly increased two years after 50% shoot length removal, and catkin production was not significantly reduced when damaged, suggesting that F(2) hybrids had great biomass tolerance and reproductive tolerance. Based on multiple regression methods, increased reproductive tolerance was associated with increased protein storage and decreased relative root:shoot ratio (reduced root allocation after damage). In addition, a positive relationship between biomass tolerance and condensed tannins was detected, and both traits were associated with increased reproductive tolerance. These four factors explained 57% of the variance in the reproductive tolerance of F(2) hybrids, but biomass tolerance explained the majority of the variance in reproductive tolerance. Changes in plant architecture in response to plant damage may be the underlying mechanism that explains biomass tolerance. PMID- 22057899 TI - Can plant resistance to specialist herbivores be explained by plant chemistry or resource use strategy? AB - At both a macro- and micro-evolutionary level, selection of and performance on host plants by specialist herbivores are thought to be governed partially by host plant chemistry. Thus far, there is little evidence to suggest that specialists can detect small structural differences in secondary metabolites of their hosts, or that such differences affect host choice or performance of specialists. We tested whether phytochemical differences between closely related plant species are correlated with specialist host choice. We conducted no-choice feeding trials using 17 plant species of three genera of tribe Senecioneae (Jacobaea, Packera, and Senecio; Asteraceae) and a more distantly related species (Cynoglossum officinale; Boraginaceae) containing pyrrolizidine alkaloids (PAs), and four PA sequestering specialist herbivores of the genus Longitarsus (Chrysomelidae). We also assessed whether variation in feeding by specialist herbivores is attributable to different resource use strategies of the tested plant species. Plant resource use strategy was quantified by measuring leaf dry matter content, which is related to both plant nutritive value and to plant investment in quantitative defences. We found no evidence that intra-generic differences in PA profiles affect feeding by specialist herbivores. Instead, our results indicate that decisions to begin feeding are related to plant resource use strategy, while decisions to continue feeding are not based on any plant characteristics measured in this study. These findings imply that PA composition does not significantly affect host choice by these specialist herbivores. Leaf dry matter content is somewhat phylogenetically conserved, indicating that plants may have difficulty altering resource use strategy in response to selection pressure by herbivores and other environmental factors on an evolutionary time scale. PMID- 22057900 TI - Effects of habitat characteristics and interspecific interactions on co occurrence patterns of saproxylic beetles breeding in tree boles after forest fire: null model analyses. AB - It is often suggested that habitat attributes and interspecific interactions can cause non-random species co-occurrence patterns, but quantifying their contributions can be difficult. Null models that systematically exclude and include habitat effects can give information on the contribution of these factors to community assembly. In the boreal forest, saproxylic beetles are known to be attracted to recently burned forests where they breed in dead and dying trees. We examined whether species co-occurrences of saproxylic beetles that develop in, and emerge from, boles of recently burned trees show non-random patterns. We also estimated the extent to which both the post-fire habitat attributes and interspecific interactions among beetles contribute to such patterns. We sampled tree boles encompassing key attributes (tree species, tree size/dbh and burn severity) that are thought to characterize species-habitat associations of saproxylic beetles, a proposition that we tested using indicator species analysis. Two null models with no habitat constraints ("unconstrained") indicated that a total of 29.4% of the species pairs tested had significant co-occurrence patterns. Habitat-constrained null models indicated that most of the detected species aggregations (72%) and segregations (59%) can be explained by shared and distinct species-habitat relationships, respectively. The assembly pattern was also driven by interspecific interactions, of which some were modulated by habitat; for example, predator and prey species tended to co-occur in large-sized trees (a proxy of available bark/wood food resource primarily for the prey). In addition, some species segregation suggesting antagonistic, competitive, or prey predator interactions were evident after accounting for the species' affinities for the same tree species. Overall, our results suggest that an intimate link between habitat and interspecific interactions can have important roles for community assembly of saproxylic assemblages even following disturbance by fire. We also show that a systematic application of null models can offer insight into the mechanisms behind the assembly of ecological communities. PMID- 22057901 TI - Analysis of glucose metabolism in cynomolgus monkeys during aging. AB - This study was designed to investigate the effect of aging on the glucose metabolism on cynomolgus (Macaca fascicularis) monkeys. A total of 33 cynomolgus monkeys in three aged groups were monitored for glucose levels, serum parameters in fasting state and somatometric measurements. Intravenous glucose tolerance test (IVGTT) and insulin tolerance test (ITT) were also performed. Aging associated changes lies in the less secretion of insulin and C-peptide during IVGTT in cynomolgus monkeys. It was also found that impaired insulin sensitivity occurred in female monkeys during aging based on HOMA-IR and K(ITT) value. In addition, triglyceride level also rose with the increase of age. Less insulin secretion and impaired insulin sensitivity in female were the characteristic during the aging of cynomolgus monkeys in this study. Body mass index, weight and waist hip rate may be the relevant factors in insulin resistance of cynomolgus monkeys. PMID- 22057902 TI - N-Acetylcysteine prevents baker's-yeast-induced inflammation and fever. AB - OBJECTIVE AND DESIGN: To investigate whether N-acetylcysteine (NAC) alters baker's-yeast-induced fever and inflammation. MATERIAL OR SUBJECTS: Male Wistar rats (26-28 days old) injected with baker's yeast (135 mg/kg, intraperitoneal) or prostaglandin E(2) (300 ng/100 MUL, intrathecal). TREATMENT: Rats were injected with NAC (500 mg/kg, subcutaneous, or 50 MUg/100 MUL, intrathecal) 1 h before, or 2 h after, pyrogen injection. METHODS: Rectal temperature changes induced by baker's yeast, PGE(2) and NAC were followed up over time. Four hours after baker's yeast injection, total leukocytes, protein, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and nonprotein thiol content were assessed in peritoneal lavage and hypothalamus. RESULTS: Systemic administration of NAC decreased leukocytes, protein, IL-1beta and TNF-alpha levels in peritoneal lavage, and decreased IL-1beta levels in the hypothalamus. The central administration of NAC prevented baker's-yeast-induced fever, but did not alter the febrile response elicited by prostaglandin E(2). CONCLUSION: These results suggest an anti-inflammatory and antipyretic role for NAC in yeast-induced peritonitis. PMID- 22057903 TI - Postnatal expression of an apamin-sensitive k(ca) current in vestibular calyx terminals. AB - Afferent innervation patterns in the vestibular periphery are complex, and vestibular afferents show a large variation in their regularity of firing. Calyx fibers terminate on type I vestibular hair cells and have firing characteristics distinct from the bouton fibers that innervate type II hair cells. Whole-cell patch clamp was used to investigate ionic currents that could influence firing patterns in calyx terminals. Underlying K(Ca) conductances have been described in vestibular ganglion cells, but their presence in afferent terminals has not been investigated previously. Apamin, a selective blocker of SK-type calcium-activated K(+) channels, was tested on calyx afferent terminals isolated from gerbil semicircular canals during postnatal days 1-50. Lowering extracellular calcium or application of apamin (20-500 nM) reduced slowly activating outward currents in voltage clamp. Apamin also reduced the action potential afterhyperpolarization (AHP) in whole-cell current clamp, but only after the first two postnatal weeks. K(+) channel expression increased during the first postnatal month, and SK channels were found to contribute to the AHP, which may in turn influence discharge regularity in calyx vestibular afferents. PMID- 22057904 TI - Tumor growth inhibited by low-voltage amplitude and 5-kHz frequency electrochemotherapy. AB - The most important unpleasant sensation of electrochemotherapy is muscle contraction. One of the causes of this discomfort is electrochemotherapy in the low-frequency range (1 Hz). To resolve this problem, there are two solutions: first, increasing the repetition frequency of electric pulses above the tetanic frequency and, second, reducing the voltage amplitude. This study examines the antitumor effectiveness of treatment using low electric fields and high frequency in the presence and absence of chemotherapeutic agents. High-voltage amplitude electrochemotherapy was performed by eight pulses, at 1,000 V/cm, of 100-MUs duration at 1-Hz and 5-kHz repetition frequency. In the low-voltage amplitude protocol, 4,000 pulses, of 100-MUs duration at 5-kHz repetition frequency with 70, 100 and 150 V/cm were delivered to invasive ductal carcinoma tumors after intratumoral injection of bleomycin. Our data demonstrate significant differences in tumor volumes and the curability rate between mice treated by 70 V/cm compared to other groups. Electrochemotherapy, which is specified by a higher repetition frequency of electric pulses (5 kHz) and low voltage, inhibits tumor growth. This protocol has a comparable effect to 1-Hz pulse repetition electric pulses with high voltage. Based on these results, the 4,000 pulses of 70 V/cm with 5-kHz frequency are most effective. This protocol demonstrates inhibition of tumor growth without any need for drug administration. PMID- 22057905 TI - Dynamics of catalytic tubular microjet engines: dependence on geometry and chemical environment. AB - Strain-engineered tubular microjet engines with various geometric dimensions hold interesting autonomous motions in an aqueous fuel solution when propelled by catalytic decomposition of hydrogen peroxide to oxygen and water. The catalytically-generated oxygen bubbles expelled from microtubular cavities propel the microjet step by step in discrete increments. We focus on the dynamics of our tubular microjets in one step and build up a body deformation model to elucidate the interaction between tubular microjets and the bubbles they produce. The average microjet velocity is calculated analytically based on our model and the obtained results demonstrate that the velocity of the microjet increases linearly with the concentration of hydrogen peroxide. The geometric dimensions of the microjet, such as length and radius, also influence its dynamic characteristics significantly. A close consistency between experimental and calculated results is achieved despite a small deviation due to the existence of an approximation in the model. The results presented in this work improve our understanding regarding catalytic motions of tubular microjets and demonstrate the controllability of the microjet which may have potential applications in drug delivery and biology. PMID- 22057906 TI - Lipids containing polyunsaturated fatty acids synthesized by zygomycetes grown on glycerol. AB - Several strains of Zygomycetes cultivated on glycerol produced mycelia rich in lipids containing higher amounts of neutral lipids (NL) than glycolipids plus sphingolipids and phospholipids (P), while biosynthesis of P in Mortierella ramanniana, Mucor sp., and Cunninghamella echinulata occurred though NL accumulation process was in progress. Polyunsaturated fatty acids (PUFA) concentration gradually decreased in all lipid fractions of M. ramanniana during growth. In contrast, in C. echinulata concentration of both linoleic and gamma linolenic acids increased with time, especially in P. Taking for granted that the main function of PUFA is associated to their participation in mycelial membranes, we could suppose that biosynthesis of these fatty acids is associated to mycelial growth. However, this is accurate only for some Zygomycetes, e.g., M. ramanniana. On the contrary, PUFA biosynthesis in C. echinulata persists after growth cessation, suggesting that in this species biosynthetic ability is not a strictly growth-associated process. Phosphatidyl-inositol and phosphatidyl-choline were the major P classes in C. echinulata and M. ramanniana, respectively. In M. ramanniana, a decrease of PUFA concentration was noticed even when mycelia were incubated in low temperature (conditions that normally favor PUFA biosynthesis), indicating that PUFA biosynthesis in this fungus is associated to primary metabolism. PMID- 22057907 TI - Decolorization of Remazol Brilliant Blue R by a purified laccase of Polyporus brumalis. AB - A white rot basidiomycete Polyporus brumalis has been reported to induce two laccase genes under degradation conditions of dibutylphthalate. When this fungus was grown in a minimal medium, one laccase enzyme was detected by the native polyacrylamide gel electrophoresis. A laccase was purified through ammonium sulfate precipitation and ion exchange chromatography, and the estimated molecular weight was 70 kDa. The optimum pH and temperature of the purified laccase was pH 4.0 and 20 degrees C, respectively. The K (m) value of the enzyme was 685.0 MUM, and the V (max) was 0.147 ODmin(-1) unit(-1) for o-tolidine. Purified laccase showed effective decolorization of a dye, Remazol Brilliant Blue R (RBBR), without any laccase mediator. However, this effect was reduced by a laccase inhibitor, kojic acid, which confirmed that the laccase was directly involved in the decolorization of RBBR. PMID- 22057908 TI - A galactomannan-driven enhancement of the in vitro multiplication rate for the Marubakaido apple rootstock (Malus prunifolia (Willd.) Borkh) is not related to the degradation of the exogenous galactomannan. AB - Agar is a complex mixture of gel-forming polysaccharides. Gelling agents are very often used to provide proper support for plants grown in semisolid culture media. And agar is the most frequently used gelling agent in plant tissue culture media. Galactomannans, another group of gel-forming polysaccharides, consists of a (1 -> 4)-linked beta-D: -mannopyranosyl backbone partially substituted at O-6 with D: galactopyranosyl side groups. In this work, we demonstrate that a statistically significant 2.7-fold increase on the multiplication rate (MR) for in vitro-grown Marubakaido (Malus prunifolia) shoots was associated with a 12.5% replacement of agar in the semi-solid culture media for a galactomannan obtained from seeds of Schizolobium paraybae. This increase on MR was due mainly to a 1.9-fold increase in the number of main branches and an 8.6-fold increase in the number of primary lateral branches. Gas liquid chromatography and thin layer chromatography analyzes demonstrated that the galactomannan-driven enhancement of the in vitro multiplication rate of the Marubakaido apple rootstock was not related to the galactomannan degradation. To the best of our knowledge, this is the first report on the successful use of partial replacement of high quality agar by a galactomannan from S. paraybae in a micropropagation system for a tree species. PMID- 22057909 TI - Preliminary studies for cephamycin C purification technique. AB - A study was made for purification of cephamycin C from fermentation of Streptomyces clavuligerus. Initially, the culture broth was clarified by microfiltration and ultrafiltration, after which the resulting permeates were subjected to nonspecific adsorption and ion-exchange chromatography on resin columns. The antibiotic activity was measured by the biological method at each stage by assaying its activity against the Escherichia coli ESS, super sensitive to beta-lactam antibiotic. The purification processes were assessed in relation to the variables affecting each step. The purification efficiency by nonspecific adsorption was monitored by UV spectrophotometry, while the ion-exchange adsorption fractions were assessed by NMR spectroscopy. Some of the fractions obtained during purification were also analyzed by mass spectrometry (LC/MS and LC/MS/MS) to identify the cephamycin C molecule. These preliminary results proved the process feasibility. PMID- 22057910 TI - Pharmacologic prophylaxis for venous thromboembolism and 30-day outcomes among older patients hospitalized with heart failure: an analysis from the ADHERE national registry linked to Medicare claims. AB - BACKGROUND: Hospitalized medically ill patients are at greater risk for venous thromboembolism (VTE). Although pharmacologic prophylaxis regimens have reduced VTE risk in medically ill patients, associations with early postdischarge adverse clinical outcomes among patients with heart failure are unknown. HYPOTHESIS: We hypothesized that patients receiving pharmacologic VTE prophylaxis during hospitalization for heart failure would have lower rates of postdischarge adverse clinical outcomes than patients not receiving prophylaxis. METHODS: Using data from the Acute Decompensated Heart Failure (ADHERE) registry linked to Medicare claims, we estimated 30-day postdischarge outcome rates for patients who received in-hospital subcutaneous heparin compared with patients who did not receive in hospital VTE prophylaxis. We excluded patients who received warfarin or intravenous heparin. Outcomes included mortality, thromboembolic events, major adverse cardiovascular events, and all-cause readmission. We used propensity score methods to estimate associations between VTE prophylaxis and each outcome. In a secondary analysis, we compared outcomes of patients receiving pharmacologic prophylaxis with unfractionated heparin (UFH) vs low-molecular-weight heparin (LMWH). RESULTS: Of 36 799 eligible patients in 265 hospitals, 12 169 (33%) received pharmacologic VTE prophylaxis during the hospitalization. In unadjusted analysis and after weighting by the inverse probability of treatment, VTE prophylaxis was not associated with 30-day postdischarge mortality, thromboembolic events, major adverse cardiovascular events, or all-cause readmission. There were no differences in outcomes between patients receiving UFH and those receiving LMWH. CONCLUSIONS: Pharmacologic VTE prophylaxis is provided to one-third of older patients hospitalized with heart failure. Treatment with LMWH or UFH did not have a statistically significant association with 30-day postdischarge outcomes. PMID- 22057911 TI - Terminating the amyloid zipper by design. PMID- 22057912 TI - Repeated coagulation testing in children. Does it improve the diagnostic value? AB - BACKGROUND: Mild bleeding disorders (BD) such as von Willebrand disease (VWD) type I are often difficult to diagnose because of inconclusive laboratory results. Our study examines the diagnostic value of repeated testing. PATIENTS, METHODS: Prospective study on 200 children. Extensive laboratory testing was done twice and a standardized history was taken. RESULTS: 165 patients completed the study (median age 5.6 years). Main reason for referral was aPTT prolongation (n = 109). The initial diagnosis was upheld in 74/165 (44.8%) children. Of 18 patients rated normal, 8 had to be reclassified as possible VWD later. Ten patients were diagnosed VWD I. In 36 patients possible VWD was found, 13 of these had normal results at the second visit while in 6 VWD became more likely. The main diagnosis was lupus-anticoagulant (n=79), normalizing in 24. A total of 88 children underwent surgery during the study period. CONCLUSION: Our study shows frequent changes in the diagnosis and highlights the limitations of single laboratory tests in detecting mild BD. Clinical and laboratory abnormalities have to be followed and tests must be repeated in unclear cases. Normal values at one point do not exclude a BD. PMID- 22057913 TI - Obstetric outcomes of IVF trichorionic triamniotic triplets which are spontaneously or electively reduced to twins. AB - PURPOSE: To assess the obstetric outcome of IVF triplets which are spontaneously or electively reduced to twins. METHODS: Retrospective study of trichorionic triplets (TT) and dichorionic twins (DT) conceived with IVF. RESULTS: Compared to TT without reduction, TT with spontaneous reduction (SR) (OR: 5.6, 95% CI: 1.6 19.9) or elective reduction (ER) (OR: 14.0, 95% CI: 3.92-50.02) to twins were significantly more likely to be delivered at >=34 weeks. Compared to DT likelihood of delivery >=34 weeks was similar for SR and ER. Compared to TT without reduction, the risk of pregnancy loss before 24 weeks was not increased with SR or ER. Compared to DT the risk of pregnancy loss before 24 weeks was not significantly increased for SR or ER. CONCLUSION: Obstetric outcome of IVF triplets with SR is better than ongoing triplets and is similar to that of ER of TT and DT. PMID- 22057914 TI - MK-2206, a novel allosteric inhibitor of Akt, synergizes with gefitinib against malignant glioma via modulating both autophagy and apoptosis. AB - Gefitinib, a small molecule inhibitor of the epidermal growth factor receptor tyrosine kinase, has been shown to induce autophagy as well as apoptosis in tumor cells. Yet, how to use autophagy and apoptosis to improve therapeutic efficacy of this drug against cancer remains to be explored. We reported here that MK-2206, a potent allosteric Akt inhibitor currently in phase I trials in patients with solid tumors, could reinforce the cytocidal effect of gefitinib against glioma. We found that cotreatment with gefitinib and MK-2206 increased the cytotoxicity of this growth factor receptor inhibitor in the glioma cells, and the CompuSyn synergism/antagonism analysis showed that MK-2206 acted synergistically with gefitinib. The benefit of the combinatorial treatment was also shown in an intracranial glioma mouse model. In the presence of MK-2206, there was a significant increase in apoptosis in glioma cells treated with gefitinib. MK-2206 also augmented the autophagy-inducing effect of gefitinib, as evidenced by increased levels of the autophagy marker, LC3-II. Inhibition of autophagy by silencing of the key autophagy gene, beclin 1 or 3-MA, further increased the cytotoxicity of this combinatorial treatment, suggesting that autophagy induced by these agents plays a cytoprotective role. Notably, at 48 hours following the combinatorial treatment, the level of LC3-II began to decrease but Bim was significantly elevated, suggesting a switch from autophagy to apoptosis. On the basis of the synergistic effect of MK-2206 on gefitinib observed in this study, the combination of these two drugs may be utilized as a new therapeutic regimen for malignant glioma. PMID- 22057915 TI - Rapamycin induces Bad phosphorylation in association with its resistance to human lung cancer cells. AB - Inhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal-regulated kinase 1 or 2 (ERK1/2) and Akt in various types of cancer cells, which contributes to rapamycin resistance. However, the downstream effect of rapamycin-activated ERKs and Akt on survival or death substrate(s) remains unclear. We discovered that treatment of human lung cancer cells with rapamycin results in enhanced phosphorylation of Bad at serine (S) 112 and S136 but not S155 in association with activation of ERK1/2 and Akt. A higher level of Bad phosphorylation was observed in rapamycin-resistant cells compared with parental rapamycin-sensitive cells. Thus, Bad phosphorylation may contribute to rapamycin resistance. Mechanistically, rapamycin promotes Bad accumulation in the cytosol, enhances Bad/14-3-3 interaction, and reduces Bad/Bcl-XL binding. Rapamycin-induced Bad phosphorylation promotes its ubiquitination and degradation, with a significant reduction of its half-life (i.e., from 53.3-37.5 hours). Inhibition of MEK/ERK by PD98059 or depletion of Akt by RNA interference blocks rapamycin-induced Bad phosphorylation at S112 or S136, respectively. Simultaneous blockage of S112 and S136 phosphorylation of Bad by PD98059 and silencing of Akt significantly enhances rapamycin-induced growth inhibition in vitro and synergistically increases the antitumor efficacy of rapamycin in lung cancer xenografts. Intriguingly, either suppression of Bad phosphorylation at S112 and S136 sites or expression of the nonphosphorylatable Bad mutant (S112A/S136A) can reverse rapamycin resistance. These findings uncover a novel mechanism of rapamycin resistance, which may promote the development of new strategies for overcoming rapamycin resistance by manipulating Bad phosphorylation at S112 and S136 in human lung cancer. PMID- 22057916 TI - Tumor suppressor microRNA-493 decreases cell motility and migration ability in human bladder cancer cells by downregulating RhoC and FZD4. AB - The purpose of this study was to identify new tumor suppressor microRNAs (miRNA; miR) in bladder cancer, conduct functional analysis of their suppressive role, and identify their specific target genes. To explore tumor suppressor miRs in bladder cancer, miR microarray was conducted using SV-HUC-1, T24, J82, and TCCSUP cells. Expression of miR-493 in bladder cancer (T24, J82, and TCCSUP) cells was downregulated compared with normal SV-HUC-1 cells. Also, the expression of miR 493 was significantly lower in bladder cancer tissues than in their corresponding noncancerous tissues. Transfection of miR-493 into T24 or J82 cells decreased their cell growth and migration abilities. On the basis of this result, to identify potential miR-493 target genes, we used target scan algorithms to identify target oncogenes related to invasion and migration. miR-493 decreased 3' untranslated region luciferase activity and protein expression of FZD4 and RhoC. miR-493 also decreased binding of RhoC and Rock-1. miR-493 is a new tumor suppressor miRNA in bladder cancer and inhibits cell motility through downregulation of RhoC and FZD4. PMID- 22057917 TI - Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case-control study. AB - We evaluated the efficacy and safety of gamma knife stereotactic radiosurgery (GKSR) followed by bevacizumab combined with chemotherapy in 11 patients with recurrent glioblastoma multiforme who experienced tumor progression despite aggressive initial multi-modality treatment. Our experience included eight male and three female patients. The median patient age at GKSR was 62 years (range 46 72 years). At the time of GKSR, seven patients had a first recurrence and four had two or more recurrences. The median interval from the initial diagnosis until GKSR was 17 months (range 5-34.5 months). The median tumor volume was 13.6 cm(3) (range 1.2-45.1 cm(3)) and the median margin dose of GKSR was 16 Gy (range 13-18 Gy). Following GKSR, bevacizumab was administrated with irinotecan in nine patients and with temozolomide in one patient. One patient was treated with bevacizumab monotherapy. The treatment outcomes were compared to 44 case-matched controls who underwent GKSR without additional bevacizumab. At a median of 13.7 months (range 4.6-28.3 months) after radiosurgery, tumor progression was evident in seven patients. The median progression-free survival (PFS) was 15 months (95% confidential interval (CI), 6.5-23.3 months). Six-month and 1-year PFS rates were 73 and 55%, respectively. The median overall survival (OS) from GKSR was 18 months (95% CI, 10.1-25.7 months) and 1-year OS rate was 73%. One patient (9%) experienced grade III toxicity and one patient (9%) had major adverse radiation effects. Compared with patients who did not receive bevacizumab, the patients who received bevacizumab had significantly prolonged PFS (15 months vs. 7 months, P = 0.035) and OS (18 months vs. 12 months, P = 0.005), and were less likely to develop an adverse radiation effect (9 vs. 46%, P = 0.037). The combination of salvage GKSR followed by bevacizumab added potential benefit and little additional risk in a small group of patients with progressive glioblastoma. Further experience is needed to define the efficacy and long-term toxicity with this strategy. PMID- 22057918 TI - Antibacterial activity and cytotoxicity of selected Egyptian medicinal plants. AB - Medicinal plants have been used as a source of remedies since ancient times in Egypt. The present study was designed to investigate the antibacterial activity and the cytotoxicity of the organic extracts from 16 selected medicinal plants of Egypt. The study was also extended to the isolation of the antiproliferative compound jaeschkeanadiol p-hydroxybenzoate (FH-25) from Ferula hermonis. The microbroth dilution was used to determine the minimal inhibitory concentration (MIC) of the samples against twelve bacterial strains belonging to four species, Providencia stuartii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, while a resazurin assay was used to assess the cytotoxicity of the extracts on the human pancreatic cancer cell line MiaPaCa-2, breast cancer cell line MCF-7, CCRF-CEM leukemia cells, and their multidrug resistant subline, CEM/ADR5000. The results of the MIC determination indicated that all the studied crude extracts were able to inhibit the growth of at least one of the tested bacterial species, the best activity being recorded with the crude extracts from F. hermonis and Vitis vinifera, whichwere active against 91.7% and 83.3% of the studied bacteria, respectively. The lowest MIC value of 128 MUg/mL was recorded against P. stuartii ATCC 29916 and E. coli ATCC 10536 with the extract from V. vinifera and Commiphora molmol, respectively. In the cytotoxicity study, IC50 values below 20 MUg/mL were recorded for the crude extract of F. hermonis on all four studied cancer cell lines. FH-25 also showed good cytotoxicity against MCF-7 cells (IC50: 2.47 MUg/mL). Finally, the results of the present investigation provided supportive data for the possible use of the plant extracts investigated herein, mostly F. hermonis and V. vinifera in the treatment of bacterial infections and jaeschkeanadiol p-hydroxybenzoate in the control of cancer diseases. PMID- 22057919 TI - Re-annotation of two hyperthermophilic archaea Pyrococcus abyssi GE5 and Pyrococcus furiosus DSM 3638. AB - Pyrococcus abyssi GE5 (P. aby) and Pyrococcus furiosus DSM 3638 (P. fur) are two model hyperthermophilic archaea. However, their annotations in public databases are unsatisfactory. In this article, the two genomes were re-annotated according to the following steps. (i) All "hypothetical genes" in the original annotation were re-identified based on the Z-curve method, and some of them were recognized as non-coding open reading frames (ORFs). Evidence showed that the recognized non coding ORFs were highly unlikely to encode proteins. (ii) The translation initiation sites (TISs) of all the annotated genes were re-located, and more than 10% of the TISs were shifted to 5'-upstream or 3'-downstream regions. (iii) The functions of the refined "hypothetical genes" were predicted using sequence alignment tools, more than 200 originally annotated "hypothetical genes" in either of the two hyperthermophiles were assigned functions. A large number of these functions have reference support or experimentally characterized homologues. All the refined information will serve as a valuable resource for research on P. aby and P. fur, which may be helpful in the exploration of thermal adaptation mechanisms. The complete re-annotation files of P. aby and P. fur are available at http://211.69.128.148/download/ . PMID- 22057920 TI - Long-term survival of Bacillus spores in alcohol and identification of 90% ethanol as relatively more spori/bactericidal. AB - This study was taken up with a view to generate basic information on spore hardiness to ethanol in various Bacillus species and related genera, and to assess the effectiveness of different levels of ethanol as a bacterial disinfectant. Predominantly spore-bearing cultures of five Bacillus spp. (B. pumilus, B. subtilis, B. megaterium, B. fusiformis and B. flexus) that were isolated from the spent-alcohol used during plant tissue culture work were challenged with aqueous ethanol (25, 50, 60, 70, 80 and 90% v/v) in 1 ml volumes at 1010-11 CFU ml-1. Monitoring the spore endurance through spotting and plating revealed prolonged tolerance (>12 months) at different alcohol levels depending on the organism except in 90% where no survival was observed beyond 2-12 months. Spores of related genera like Paenibacillus and Lysinibacillus also showed long term ethanol survival. Alcohol tolerance of spore-forming organisms depended on the extent of spores and spore hardiness, which in turn varied with the organism, strain, age of culture, growing conditions and other factors as authenticated with ATCC strains of B. pumilus and B. subtilis. Aqueous 90% ethanol caused instant inactivation of vegetative cells in different spore formers and twelve other non-sporulating Gram-positive and Gram-negative organisms tested. Taking into account both vegetative cells and spores, the appropriate concentration of ethanol as a disinfectant emerged to be 90% followed by absolute ethanol compared with the generally recommended 70-80% level. PMID- 22057921 TI - Isolation and identification of endophytic fungi in roots of nine Holcoglossum plants (Orchidaceae) collected from Yunnan, Guangxi, and Hainan provinces of China. AB - Holcoglossum is one of the smaller genera of Orchidaceae, mainly distributed in southwest China. Some members of this genus as well as H. rupestre and H. flavescens are endemic and rare Chinese orchids. As far as we know, little work has been done concerning the relationships between the Holcoglossum plants and endophytic microorganisms. In this study, 46 culturable fungal endophytes were isolated and identified from roots of nine Holcoglossum plants collected from Yunnan, Guangxi, and Hainan provinces of China based on molecular techniques. The results showed that all strains belonged to four classes, i.e., Sordariomycetes (41.30%), Dothideomycetes (36.96%), Agaricomycetes (17.39%), Leotiomycetes (4.35%). Thirty-six strains were identified at the genus level, including Alternaria, Cladosporium, Clonostachys, Colletotrichum, Cosmospora, Cryptosporiopsis, Cylindrocarpon, Didymella, Epulorhiza (Anamorphic Tulasnella), Fusarium, Myrmecridium, Leptosphaeria, Paraconiothyrium, Phomopsis, Pyrenochaeta, and Stephanonectria. Fusarium and Epulorhiza (Anamorphic Tulasnella) were the dominant fungal endophytes. Some orchids mycorrhizal fungi as well as Tulasnella calospora and Epulorhiza sp. were found in roots. This is the first report concerning endophytic fungi from Holcoglossum plants (Orchidaceae), suggesting that endophytic fungi in Holcoglossum plants are very abundant. PMID- 22057922 TI - Biologically inhibitory effects of VEGF siRNA on endometrial carcinoma cells. AB - OBJECTIVE: To study the biological effects of small inhibitory RNA (siRNA) on endometrial carcinoma cells through disrupting the mRNA of Vascular endothelial growth factor (VEGF), and its inhibitory functions on tumor cells' proliferation. METHODS: The sequence-specific siRNA of VEGF165 and the mock siRNA were designed, they were transfected into the endometrial carcinoma cell line, Ishikawa cells. Total cell RNAs were extracted from the transfected cells. The mRNA levels of VEGF were then analyzed utilizing real-time fluorescence quantitative RT-PCR (FQ PCR) post-transfection at 12, 24, 48, 72, and 168 h, respectively. Simultaneously its protein levels were also determined by western blot. Cell proliferations were monitored by MTT assay and cytopathological effects (CPE) were determined by Multispect Imaging System. RESULT: The mRNA and protein levels of VEGF declined post-transfection at 12, 24, 48, 72 h, respectively, with a maximum decrease post transfection at 48 h. The proliferation of Ishikawa cells was significantly inhibited in a similar manner during this time window. All the data were repeated at least three independent times and similar results were achieved. CONCLUSION: The small siRNA of VEGF165 can effectively down-regulate its target mRNA and protein levels; consequently proliferation of Ishikawa cells was inhibited. The data strongly imply that VEGF may be involved in the genesis of endometrial carcinoma, which provides a new pathway to treat human endometrial caners. PMID- 22057923 TI - CONTSOR--a new knowledge-based fold recognition potential, based on side chain orientation and contacts between residue terminal groups. AB - Recognizing the structural similarity without significant sequence identity (fold recognition) is an effective method for protein structure prediction. Previously, we developed a fold recognition potential called SORDIS, which incorporated side chain orientation in relation to hydrophobic core centers, distance of the residues from the protein globule center and secondary structure terms. But this potential does not include terms, based on close contacts between residues. In this paper a new fold recognition potential CONTSOR was presented, which based on SORDIS terms and the term, based on contacts between amino acid terminal groups. The performance of this potential was evaluated on SABmark benchmark for alignment accuracy and on SABmark and Lindahl benchmarks for fold recognition. The results show that CONTSOR has the best performance among other potentials on SABmark benchmark both for alignment accuracy and fold recognition and one of the best performances on Lindahl benchmark. CONTSOR software package is available for download at http://www.lifescience.org.ge/downloads/contsor.zip. PMID- 22057924 TI - Epithelia, an evolutionary novelty of metazoans. AB - At the point in animal evolution when cells began to adhere to each other they presumably initially functioned as colonies. The formation of an epithelium that enclosed and controlled an internal milieu would have been the first event to distinguish an individual animal from a colony. To better understand when the first epithelium arose and what its characteristics were, we evaluate the morphological, functional, and molecular characters of epithelia in sponges, considered here the extant representatives of the first metazoans. In particular, we show new claudin-like sequences from sponges align most closely with sequences from Drosophila that have a barrier function in septate junctions. We also show that type IV collagen, the main component of the basement membrane (BM), is present in calcareous sponges, and we confirm the presence of type IV-like collagen (spongin short chain collagen) in other sponges. Though in sponges as in other metazoans the epithelium has grades of specialization with varying complexity of junctions and the BM, the main character of a functional epithelium, the ability to seal and control the ionic composition of the internal milieu, is a property of even the simplest sponge epithelium, and therefore the first metazoans likely also had epithelia with these characteristics, which we consider a "true" epithelium. PMID- 22057925 TI - Bacteriologic and nutritional evaluation of a commercial raw meat diet as part of a raw meat safety program. AB - This study evaluated selected bacteriologic and nutritional components of a commercially prepared ground raw horsemeat diet as part of a raw meat safety program. Six lots of meat were analyzed in triplicate. Frozen meat samples were thawed for 44 hr at 5 degrees C. Meat samples were tested at three times during thawing (t = 0, 24, 44 hr) for selected bacteria. Samples were screened for Salmonella sp. using an enzyme-linked immunosorbent assay. Escherichia coli and total coliform bacteria were quantified using a ready-made culture medium system. Proximate, energy, macro and trace mineral composition was determined at a reference laboratory. Salmonella sp. antigen was detected in one sample of meat at t = 0 hr. Frozen meat samples had low average maximum expected numbers of E. coli and coliforms. The average maximum number of E. coli did not change significantly at t = 24 or 44 hr, but the average maximum number of coliforms increased significantly by t = 44 hr. These bacteriologic tests were easily incorporated into a raw meat safety program. Median concentrations of moisture, dry matter, crude protein, crude fat, ash, calcium, and phosphorus conformed to the guaranteed analysis but median crude fiber exceeded the guaranteed maximum. Median magnesium, potassium, and sodium concentrations conformed to the approximate nutrient content. Median concentrations of copper exceeded, whereas iron, zinc, and manganese fell below, the approximate nutrient content. Median copper and manganese concentrations exceeded the National Research Council's recommendation for adult domestic cats, whereas iron and zinc were below the National Research Council's recommendations for adult cats. PMID- 22057926 TI - Health, migration and border management: analysis and capacity-building at Europe's borders. AB - OBJECTIVES: Three key elements were analysed in Hungary, Poland and Slovakia as a basis for strengthening the capacity of staff and structures related to health, migration and border management: public health concerns linked to migration, health needs and rights of migrants and the occupational health of staff. METHODS: This IOM project was implemented through an in-depth situation analysis as well as the development of training modules and public health guidelines. RESULTS: Findings indicate a paucity of existing data, gaps in the health care for migrants and few existing tools for border officials and health professionals. Sets of training modules were developed for each of these groups, including common modules on migration and the right to health and intercultural communication, as well as targeted health modules. The guidelines promote good practices in the context of border management and detention. CONCLUSIONS: The EU is working towards a common immigration policy and integrated border management; however, a harmonized approach to migration and health is still lacking. Further research and piloting of the developed materials is needed to fully establish an adaptable, common toolkit. PMID- 22057927 TI - Experimental climate warming decreases photosynthetic efficiency of lichens in an arid South African ecosystem. AB - Elevated temperatures and diminished precipitation amounts accompanying climate warming in arid ecosystems are expected to have adverse effects on the photosynthesis of lichen species sensitive to elevated temperature and/or water limitation. This premise was tested by artificially elevating temperatures (increase 2.1-3.8 degrees C) and reducing the amounts of fog and dew precipitation (decrease 30.1-31.9%), in an approximation of future climate warming scenarios, using transparent hexagonal open-top warming chambers placed around natural populations of four lichen species (Xanthoparmelia austroafricana, X. hyporhytida , Xanthoparmelia. sp., Xanthomaculina hottentotta) at a dry inland site and two lichen species (Teloschistes capensis and Ramalina sp.) at a humid coastal site in the arid South African Succulent Karoo Biome. Effective photosynthetic quantum yields ([Formula: see text]) were measured hourly throughout the day at monthly intervals in pre-hydrated lichens present in the open-top warming chambers and in controls which comprised demarcated plots of equivalent open-top warming chamber dimensions constructed from 5-cm-diameter mesh steel fencing. The cumulative effects of the elevated temperatures and diminished precipitation amounts in the open-top warming chambers resulted in significant decreases in lichen [Formula: see text]. The decreases were more pronounced in lichens from the dry inland site (decline 34.1-46.1%) than in those from the humid coastal site (decline 11.3-13.7%), most frequent and prominent in lichens at both sites during the dry summer season, and generally of greatest magnitude at or after the solar noon in all seasons. Based on these results, we conclude that climate warming interacting with reduced precipitation will negatively affect carbon balances in endemic lichens by increasing desiccation damage and reducing photosynthetic activity time, leading to increased incidences of mortality. PMID- 22057928 TI - [Preparedness for influenza A/H5N1 pandemic in Niger: a study on health care workers' knowledge and global organization of health activities]. AB - In industrialized countries, the emergence of potentially pandemic influenza virus has invited reactions consistent with the potential threat represented by these infectious agents. However, with globalization, controlling epidemics depends as much on an effective global coordination of control methods as on preparedness of northern and southern national health care systems, at the core of which are health care workers. Our study was conducted in the National Hospital of Niamey, the main Nigerian hospital. Its objective was to evaluate the knowledge of health care professionals regarding flu pandemic and control of infection. We interviewed 178 nursing staff, doctors and paramedics on the basis of a survey. This study - the first to our knowledge to explore these issues in the African context-revealed that caregivers have a rather good mastery of theoretical knowledge. Nevertheless, beyond theoretical knowledge, miscellaneous factors compromise the effectiveness of the health care structure. Some of them seem to occupy a critical position, particularly the absence of shared references among sanitary authorities and health care professionals, and the weaknesses of global coordination of preventive activities and case management. PMID- 22057929 TI - The fate of arsenic in soil-plant systems. AB - Arsenic is a natural trace element found in the environment. In some cases and places, human activities have increased the soil concentration of As to levels that exceed hazard thresholds. Amongst the main contributing sources of As contamination of soil and water are the following: geologic origin, pyriticmining, agriculture, and coal burning. Arsenic speciation in soils occurs and is relatively complex. Soils contain both organic and inorganic arsenic species. Inorganic As species include arsenite and arsenate, which are the most abundant forms found in the environment. The majority of As in aerated soils exists as H2AsO4- (acid soils) or HAsO42- (neutral species and basic). However, HA3sO3 is the predomiant anaerobic soils, where arsenic availability is higher and As(III) is more weakly retained in the soil matrix than is As(V). The availability of As in soils is usually driven by multiple factors. Among these factors is the presence of Fe-oxides and/or phosphorus, (co)precipitation in salts, pH, organic matter, clay content, rainfall amount, etc. The available and most labile As fraction can potentially be taken up by plant roots, although the concentration of this fraction is usually low. Arsenic has no known biological function in plants. Once inside root cells, As(V) is quickly reduced to As(III), and, in many plant species, becomes complexed. Phosphorus nutrition influences As(V) uptake and toxicity in plants, whilst silicon has similar influences on As(III). Plants cope with As contamination in their tissues by possessing detoxification mechanisms. Such mechanisms include complexation and compartmentalization. However, once these mechanisms are saturated, symptoms of phytotoxicity appear. Phytotoxic effects commonly observed from As exposure includes growth inhibition, chlorophyll degradation, nutrient depletion and oxidative stress. Plants vary in their ability to accumulate and tolerate As (from tolerant hyperaccumulators to sensitive excluders), and some plants are useful for soil reclamation and in sustainable agriculture, The status of current scientific knowledge allows us to manage As contamination in the soil-plant system and to mitigate arsenic's effects. Phytoremediation is an emerging technology suitable for reclaiming As-contaminated soils and waters. Phytoextraction has been used to clean As-contaminated soils, although its applicability has not yet reached maturity. Phytostabilization has been employed to reduce environmental risk by confining As as an inert form in soils and has shown success in both laboratory experiments and in field trials. Phytofiltration has been used to treat As-enriched waters. Such treatment removes As when it is accumulated in plants grown in or on water. In agricultural food production, appropriate soil management and plant variety/species selection can minimize As associated human dis- eases and the transfer of As within the food chain. Selecting suitable plants for use on As-contaminated soils may also enhance alternative land use, such as for energy or raw material production. PMID- 22057930 TI - Evaluating the toxicity of selected types of nanochemicals. AB - Nanotechnology is a fast growing field that provides for the development of materials that have new dimensions, novel properties, and a broader array of applications. Various scientific groups are keen about this technology and are devoting themselves to the development of more, new, and better nanomaterials. In the near future, expectations are that no field will be left untouched by the magical benefits available through application of nanotechnology. Presently, there is only limited knowledge concerning the toxicological effects of NPs. However, it is now known that the toxic behavior of NPs differ from their bulk counterparts. Even NPs that have the same chemical composition differ in their toxicological properties; the differences in toxicity depend upon size, shape, and surface covering. Hence, before NPs are commercially used it is most important that they be subjected to appropriate toxicity evaluation. Among the parameters of NPs that must be evaluated for their effect on toxicity are surface charges, types of coating material, and reactivity of NPs. In this article, we have reviewed the literature pertinent to the toxicity of metal oxide NPs, metallic NPs, quantum dots (QDs), silica (SiO2) NPs, carbon nanotubes (CNTs), and certain other carbon nanomaterials (NMs). These NPs have already found a wide range of applications around the world. In vitro and in vivo studies on NPs have revealed that most are toxic to animals. However, their toxic behavior varies with their size, shape, surface charge, type of coating material and reactivity. Dose, route of administration, and exposure are critical factors that affect the degree of toxicity produced by any particular type of NP. It is for this reason that we believe a careful and rigorous toxicity testing is necessary before any NP is declared to be safe for broad use. We also believe that an agreed upon testing system is needed that can be used to suitably, accurately, and economically assess the toxicity of NPs. NPs have produced an array of different toxic effects in many different types of in vivo and in vitro studies. The types of effects that NPs have produced are those on the pulmonary, cardiac, reproductive, renal and cutaneous systems, as well as on various cell lines. After exposures, significant accumulations of NPs have been found in the lungs, brain, liver, spleen, and bones of test species. It has been well established that the degree of toxicity produced by NPs is linked to their surface properties. Soluble NPs are rendered toxic because of their constituents; however, the situation is entirely different for insoluble NPs. Stable metal oxides do not show any toxicity, whereas metallic NPs that have redox potential may be cytotoxic and genotoxic. The available data on NP toxicity is unfortunately limited, and hence, does not allow scientists to yet make a significant quantitative risk assessment of the safety of synthesized NPs. In this review, we have endeavored to illustrate the importance of having and using results from existing nanotoxicological studies and for developing new and more useful future risk assessment systems. Increased efforts of both an individual and collective nature are required to explore the future pros and cons of nanotechnology. PMID- 22057931 TI - Adsorption and desorption of chlorpyrifos to soils and sediments. AB - Chlorpyrifos, one of the most widely used insecticides, has been detected in air, rain, marine sediments, surface waters, drinking water wells, and solid and liquid dietary samples collected from urban and rural areas. Its metabolite, TCP, has also been widely detected in urinary samples collected from people of various age groups. With a goal of elucidating the factors that control the environmental contamination, impact, persistence, and ecotoxicity of chlorpyrifos, we examine, in this review, the peer-reviewed literature relating to chlorpyrifos adsorption and desorption behavior in various solid-phase matrices. Adsorption tends to reduce chlorpyrifos mobility, but adsorption to erodible particulates, dissolved organic matter, or mobile inorganic colloids enhances its mobility. Adsorption to suspended sediments and particulates constitutes a major off-site migration route for chlorpyrifos to surface waters, wherein it poses a potential danger to aquatic organisms. Adsorption increases the persistence of chlorpyrifos in the environment by reducing its avail- ability to a wide range of dissipative and degradative forces, whereas the effect of adsorption on its ecotoxicity is dependent upon the route of exposure. Chlorpyrifos adsorbs to soils, aquatic sediments, organic matter, and clay minerals to differing degrees. Its adsorption strongly correlates with organic carbon con- tent of the soils and sediments. A comprehensive review of studies that relied on the batch equilibrium technique yields mean and median Kd values for chlorpyrifos of 271 and 116 L/kg for soils, and 385 and 403 L/kg for aquatic sediments. Chlorpyrifos adsorption coefficients spanned two orders of magnitude in soils. Normalizing the partition coefficient to organic content failed to substantially reduce variability to commonly acceptable level of variation. Mean and median values for chlorpyrifos partition coefficients normalized to organic carbon, K, were 8,163 and 7,227 L/kg for soils and 13,439 and 15,500 L/kg for sediipents. This variation may result from several factors, including various experimental artifacts, variation in quality of soil organic matter, and inconsistencies in experimental methodologies. Based on this review, there appears to be no definitive quantification of chlorpyrifos adsorption or desorption characteristics. Thus, it is difficult to predict its adsorptive behavior with certainty, without resorting to experimental methods specific to the soil or sediment of interest. This limitation should be recognized in the context of current efforts to predict the risk, fate, and transport of chlorpyrifos based upon published partition coefficients. Based on a comprehensive review of the peer-reviewed literature related to adsorption and desorption of chlorpyrifos, we propose the following key areas for future research. From this review, it becomes increasingly evident that pesticide partitioning cannot be fully accounted for by the fraction of soil or solid matrix organic matter or carbon content. Therefore, research that probes the variation in the nature and quality of soil organic matter on pesticide adsorption is highly desirable. Pesticide persistence and bioavailability depend on insights into desorption capacity. Therefore, understanding the fate and environmental impact of hydrophobic pesticides is incomplete without new research being performed to improve insights into pesticide desorption from soils and sediments. There is also a need for greater attention and consistency in developing experimental methods aimed at estimating partition coefficients. Moreover, in such testing, choosing initial concentrations and liquid-solid ratios that are more representative of environmental conditions could improve usefulness and interpretation of data that are obtained. Future monitoring efforts should include the sampling and analysis of suspended particulates to account for suspended solid-phase CPF, a commonly underestimated fraction in surface water quality monitoring programs. Finally, management practices related to the reduction of off-site migration of CPF should be further evaluated, including alternative agricultural practices leading to reduction in soil erosion and structural best management practices, such as sedimentation ponds, treatment wetlands, and vegetated edge-of-field strips. PMID- 22057932 TI - Specific alterations of the HtrA2/HAX-1 ratio in the penumbra upon focal cerebral ischemia in mice. AB - HAX-1 is a mitochondrial protein which acts as an antiapoptotic protein in HeLa- and Jurkat cells after Fas-treatment, irradiation or serum deprivation. This underlines the evidence that HAX-1 might be involved in several apoptotic pathways. In this context, it is known that cell death executed by cerebral ischemia involves both receptor- and mitochondrial apoptotic mechanisms. In this study, we performed focal cerebral ischemia in mice and investigated principally the dynamic changes of HAX-1 expression and other apoptotic agents such as HtrA2, AIF and caspase-3. Western blot and immunohistochemistry analysis revealed that HAX-1 was expressed at very low levels under normal conditions. Focal cerebral ischemia significantly decreased cytosolic accumulation of HAX-1, induced an upregulation of HtrA2, an upregulation of AIF and activation of caspase-3. Taken together, these results suggested that HAX-1 is probably involved in the pathophysiology of cell death induced by focal ischemia. PMID- 22057933 TI - Secondary prevention of hyperkalemia with sodium polystyrene sulfonate in cardiac and kidney patients on renin-angiotensin-aldosterone system inhibition therapy. AB - BACKGROUND: Hyperkalemia, induced by renin-angiotensin-aldosterone system inhibition (RAAS-I) in patients with chronic kidney disease (CKD), or cardiac disease often leads to withdrawal of RAAS-I therapy. Sodium polystyrene sulfonate (SPS) is a potassium-binding resin used for the treatment of hyperkalemia. Recently, concerns about the safety and efficacy of SPS were raised. We report here a follow-up of 14 patients with CKD and heart disease on RAAS-I treatment who were treated with low-dose daily SPS to prevent recurrence of hyperkalemia. HYPOTHESIS: Daily SPS is safe and effective for secondary prevention of hyperkalemia induced by RAAS-I therapy in CKD patients with heart disease. METHODS: We reviewed the medical charts of the patients with CKD (nondialysis patients) and heart disease treated in our CKD clinic from 2005 to 2010 and identified all patients on RAAS-I therapy who were treated with daily SPS (sorbitol-free) after episodes of hyperkalemia. Data on hospitalizations, symptoms that may be attributed to SPS therapy, and electrolyte concentration levels were obtained. RESULTS: Fourteen patients were treated with low-dose SPS therapy for a total of 289 months (median length of follow-up, 14.5 months). None of the patients developed colonic necrosis or life-threatening events that could be attributed to SPS use. Mild hypokalemia was noted in 2 patients and responded to reducing the dose of SPS. No further episodes of hyperkalemia were recorded while patients were on the therapy. SPS was well-tolerated during the follow-up without need for withdrawal or reduction of the dose of RAAS-I therapy by any patients. CONCLUSIONS: Low-dose SPS was safe and effective as a secondary preventive measure for hyperkalemia induced by RAAS-I in CKD patients with heart disease. PMID- 22057934 TI - Bacterial expression, purification and characterization of a rice voltage dependent, anion-selective channel isoform, OsVDAC4. AB - The voltage-dependent anion-selective channel (VDAC) is the most abundant protein in the mitochondrial outer membrane and forms the major conduit for metabolite transport across this membrane. VDACs from different sources show varied primary sequence but conserved functional properties. Here, we report on the characterization of a rice channel, OsVDAC4, which complements a VDAC1 deficiency in yeast. We present a consensus secondary structure prediction of an N-terminal alpha-helix and 19 beta-strands. Bacterially expressed OsVDAC4 was purified from inclusion bodies into detergent-containing solution, where it is largely helical. Detergent-solubilized OsVDAC4 inserts spontaneously into artificial membranes of two topologies-spherical liposomes and planar bilayers. Insertion into liposomes results in an increase in beta-structure. Transport of polyethylene glycols was used to estimate a pore diameter of ~2.6 nm in liposomes. Channels formed in planar bilayers exhibit large conductance (4.6 +/- 0.3 nS in 1 M KCl), strong voltage dependence and weak anion selectivity. The open state of the channel is shown to be permeable to ATP. These data are consistent with a large beta-barrel pore formed by OsVDAC4 on inserting into membranes. This study forms a platform to carry out studies of the interaction of OsVDAC4 with putative modulators. PMID- 22057935 TI - On-line characterization of metabolic state in batch cultivation of Clostridium diolis for 1,3-propanediol production using NADH+H+ fluorescence. AB - NADH is a coenzyme which plays a central role in cellular growth and metabolism. It is an intracellular fluorophore which fluoresces at 460 nm when cells are irradiated by 340 nm wavelength of light. The application of NADH+H(+) fluorescence measurement for characterization of biomass and its metabolic activity during batch fermentation of 1,3-propanediol (1,3-PD) using Clostridium diolis was investigated in this study. A linear correlation between net fluorescence and biomass concentration was observed during both the initial and final phases of 1,3-PD fermentation. This could be used as an on-line indicator of biomass concentration inside the bioreactor thereby eliminating the need for sampling and off-line analysis for establishing biomass concentration during these phases. Also a sharp decline in the NADH+H(+) fluorescence value was obtained towards the end of fermentation which could be a significant on-line, in situ signal of substrate depletion in the bioreactor and therefore possible fresh nutrient feed for enhanced production of 1,3-PD by repetitive and/or various fed batch cultivation(s). This is the first report on the use of NADH + H(+) fluorescence measurement technique for 1,3-PD fermentation. PMID- 22057936 TI - Molecular analysis of OsLEA4 and its contributions to improve E. coli viability. AB - OsLEA4, a late embryogenesis abundant (LEA) protein gene from rice (Oryza sativa L.), contains a 312-bp open reading frame encoding a putative polypeptide of 103 amino acids with a calculated molecular mass of 11.19 kDa and a theoretical pI of 10.04. OsLEA4 polypeptide is rich in Ala (22%), Lys (15%), Glu (9%), His (8%), Thr (8%), and Arg (7%) and lacking in Trp, Cys, Asn, and Phe residues. OsLEA4 protein contains a Pfam:LEA_1 domain architecture at positions 1-73 with three alpha-helical domains and without beta-sheet domain. In silico predictions showed that OsLEA4 protein was strongly hydrophilic with the grand average of hydropathy value of -0.816 and instability index of 27.31. The hydrophilic regions were found in the conserved motif of OsLEA4. OsLEA4 gene was introduced into Escherichia coli, and a fusion protein (~29.4 kDa) was expressed after isopropylthio-beta-D: -galactoside inducting by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis. OsLEA4 protein enhanced the tolerance of E. coli recombinant to high salinity, heat, freezing, and UV radiation, which suggested that OsLEA4 protein may play a protective role under stressed conditions. This is the first successful use of E. coli as a prokaryotic system for LEA production from rice. PMID- 22057937 TI - Trifluoroethanol-induced changes in activity and conformation of manganese containing superoxide dismutase. AB - Superoxide dismutase (SOD, EC 1.15.1.1) plays an important role in antioxidant defense in organisms exposed to oxygen. However, there is a lack of research into the regulation of SOD activity and structural changes during folding, especially for SOD originating from extremophiles. We studied the inhibitory effects of trifluoroethanol (TFE) on the activity and conformation of manganese-containing SOD (Mn-SOD) from Thermus thermophilus. TFE decreased the degree of secondary structure of Mn-SOD, which directly resulted in enzyme inactivation and disrupted the tertiary structure of Mn-SOD. The kinetic studies showed that TFE-induced inactivation of Mn-SOD is a first-order reaction and that the regional Mn contained active site is very stable compared to the overall structure. We further simulated the docking between Mn-SOD and TFE (binding energy for Dock 6.3, -9.68 kcal/mol) and predicted that the LEU9, TYR13, and HIS29 residues outside of the active site interact with TFE. Our results provide insight into the inactivation of Mn-SOD during unfolding in the presence of TFE and allow us to describe ligand binding via inhibition kinetics combined with computational predictions. PMID- 22057938 TI - Selection of a new whole cell biocatalyst for the synthesis of 2-deoxyribose 5 phosphate. AB - 2-deoxyribose 5-phosphate (DR5P) is a key intermediate in the biocatalyzed preparation of deoxyribonucleosides. Therefore, DR5P production by means of simpler, cleaner, and economic pathways becomes highly interesting. One strategy involves the use of bacterial whole cells containing DR5P aldolase as biocatalyst for the aldol addition between acetaldehyde and D: -glyceraldehyde 3-phosphate or glycolytic intermediates that in situ generate the acceptor substrate. In this work, diverse microorganisms capable of synthesizing DR5P were selected by screening several bacteria genera. In particular, Erwinia carotovora ATCC 33260 was identified as a new biocatalyst that afforded 14.1-mM DR5P starting from a cheap raw material like glucose. PMID- 22057939 TI - Molecular cloning and characterization of a putative cDNA encoding endoglucanase IV from Trichoderma viride and its expression in Bombyx mori. AB - The development of cellulase production technology has greatly contributed to the successful use of cellulosic materials as renewable carbon sources. In this study, a putative endoglucanase IV (EG IV) complementary DNA was cloned from the mycelium of a strain of the filamentous fungus Trichoderma viride using a PCR based exon-splicing method and expressed in both a silkworm BmN cell line and in silkworm larvae. Western blot analysis detected a band of 42 kDa in BmN cells after infection with a recombinant mBacmid/BmNPV/EG IV baculovirus. Sequence alignment analysis of the T. viride EG IV gene showed two domains that were highly conserved with glycosyl hydrolases and a funga-type cellulose-binding domain. Analysis of variance showed that silkworms infected with recombinant baculoviruses exhibited significantly higher enzyme activity that was 48.84% higher than silkworms infected with blank baculoviruses and 46.61% higher than normal silkworms. The expressed bioactive EG IV was also stable at the pH range from 5.0 to 10.0. The availability of large quantities of bioactive EG IV in silkworm provided a possibility to produce cellulase transgenic silkworm, which express bioactive cellulase specially in its digestive tract and improve its metabolism efficiency of mulberry leaves. Its application in the sericulture industry may be very promising. PMID- 22057940 TI - Production, partial characterization, and use of a red biochrome produced by Serratia sakuensis subsp. nov strain KRED for dyeing natural fibers. AB - We have described a novel red biochrome, 514 Da in size, produced by solid-state cultivation of a bacterial isolate obtained from garden soil. The growth requirements of the isolate, the chemical characteristics of the biochrome produced, and the application of the biochrome in dying of silk, wool, and cotton fabrics have been studied. The biochrome obtained after 52 h of incubation and having a lambda (max) of 535 nm was used for dyeing the fabrics. We found that silk, wool, and cotton fabrics dyed with this new natural red compound have high color strength values and dye uptake along with good color fastness as well as antibacterial activity. PMID- 22057941 TI - Postural control, motor skills, and health-related quality of life in children with hearing impairment: a systematic review. AB - Children with hearing impairment have balance and motor deficits primarily due to concomitant damage to the vestibular structures. Psycho-intellectual and social developmental disorders, as well as elimination of social activities and participation may diminish health-related quality of life in these children. Despite the documentation, assessment of balance, motor deficits, and health related quality of life of these children are not included in the educational program, unless obvious neurological or orthopedic disorders are diagnosed. The objective of this review was to systematically analyze the available information in the literatures regarding the postural control, motor skills, and health related quality of life in children with hearing impairment. Searches of data sources PubMed, MEDLINE, CINHAL, EMBASE, SCOPUS, ISI of web science, Cochrane Library, and AMED database were performed from the earliest to 7 February 2011. Study eligibility criteria included non-interventional studies that addressed postural control, motor skills, and health-related quality of life in children with hearing impairment. For each eligible article, data were extracted using custom-designed forms by a single investigator. Collected data included study demographics, study design, study population, sample size, outcome measures, and results. A total of 11,872 articles were retrieved, and 17 articles were found to be eligible for inclusion. Of the 17 articles included, five articles analyzed health-related quality of life alone, two articles analyzed balance alone, two articles analyzed motor performance alone, two articles analyzed vestibular dysfunction alone, two articles included both vestibular dysfunction and balance, two articles included both motor performance and balance, and two articles investigated vestibular, balance as well as motor impairments. Heterogeneity of the studies prevented us from performing methodological quality assessment and meta-analysis. The results of this review suggest that children with hearing impairment exhibit suboptimal levels of function in postural control, motor skill performance, and health-related quality of life. PMID- 22057942 TI - Robert Mulvey. PMID- 22057943 TI - An iterative self-refining and self-evaluating approach for protein model quality estimation. AB - Evaluating or predicting the quality of protein models (i.e., predicted protein tertiary structures) without knowing their native structures is important for selecting and appropriately using protein models. We describe an iterative approach that improves the performances of protein Model Quality Assurance Programs (MQAPs). Given the initial quality scores of a list of models assigned by a MQAP, the method iteratively refines the scores until the ranking of the models does not change. We applied the method to the model quality assessment data generated by 30 MQAPs during the Eighth Critical Assessment of Techniques for Protein Structure Prediction. To various degrees, our method increased the average correlation between predicted and real quality scores of 25 out of 30 MQAPs and reduced the average loss (i.e., the difference between the top ranked model and the best model) for 28 MQAPs. Particularly, for MQAPs with low average correlations (<0.4), the correlation can be increased by several times. Similar experiments conducted on the CASP9 MQAPs also demonstrated the effectiveness of the method. Our method is a hybrid method that combines the original method of a MQAP and the pair-wise comparison clustering method. It can achieve a high accuracy similar to a full pair-wise clustering method, but with much less computation time when evaluating hundreds of models. Furthermore, without knowing native structures, the iterative refining method can evaluate the performance of a MQAP by analyzing its model quality predictions. PMID- 22057944 TI - Efficacy comparisons of the intraarticular steroidal agents in the patients with knee osteoarthritis. AB - Osteoarthritis is a chronic disease that causes serious pain and limitations in activities. Intraarticular corticosteroid injections combined with pharmacological treatment and physiotherapy have been used for years to control the local inflammation and relieve pain in the patients with osteoarthritis. There are several animal experiments which suggested that the intraarticular corticosteroid injections impair cartilage protein synthesis. However, there are no serious evidences suggesting the increase of cartilage impairment. The aim of our study was to compare the efficacy of placebo and intraarticular corticosteroid agents in the patients with symptomatic knee osteoarthritis. One hundred and twenty patients with painful knee osteoarthritis were included in the prospective, randomized, controlled study. The patients were randomized into four groups. Each group consisted of thirty patients. Intraarticular single dose of methylprednisolone acetate (40 mg, 1 ml), Betametazone disodium phosphate (3 mg, 1 ml), Triamsinolon acetonate (40 mg, 1 ml), and serum physiological (0.09% NaCl, 1 ml) were administrated to the groups, respectively. The patients were evaluated by Visual Analog Scale (0-10 cm [VAS]) for the pain severity, and by Lequesne Functional Index for functional state before treatment, and at the 1st, 3rd, 6th, and 12th weeks. Our results showed that single doses of three agents provided symptomatic and functional relief and their effects reduced at the 12th week. However, methylprednisolone acetate was a statistically more effective analgesic as compared to the other agents until the sixth week. PMID- 22057945 TI - Micro-ring structures stabilize microdroplets to enable long term spheroid culture in 384 hanging drop array plates. AB - Using stereolithography, 20 different structural variations comprised of millimeter diameter holes surrounded by trenches, plateaus, or micro-ring structures were prepared and tested for their ability to stably hold arrays of microliter sized droplets within the structures over an extended period of time. The micro-ring structures were the most effective in stabilizing droplets against mechanical and chemical perturbations. After confirming the importance of micro ring structures using rapid prototyping, we developed an injection molding tool for mass production of polystyrene 3D cell culture plates with an array of 384 such micro-ring surrounded through-hole structures. These newly designed and injection molded polystyrene 384 hanging drop array plates with micro-rings were stable and robust against mechanical perturbations as well as surface fouling facilitated droplet spreading making them capable of long term cell spheroid culture of up to 22 days within the droplet array. This is a significant improvement over previously reported 384 hanging drop array plates which are susceptible to small mechanical shocks and could not reliably maintain hanging drops for longer than a few days. With enhanced droplet stability, the hanging drop array plates with micro-ring structures provide better platforms and open up new opportunities for high-throughput preparation of microscale 3D cell constructs for drug screening and cell analysis. PMID- 22057946 TI - Evidence of prophylaxis treatment in adult haemophiliacs. Need of this treatment strategy? AB - In contrast to children with haemophilia the scientific evidence of prophylaxis treatment in adults is not yet proven. Existing studies are of observational character and mostly retrospectively designed. Therefore, opinion leaders in this field postulate prospectively designed, randomized, controlled and multicentric studies to set up urgently needed guidelines. Evidence according to the Canadian task force ranking is assessed as level III with a recommendation grade C by the authors. The recognition of benefits of health care providers in accordance with the German Federal Joint Committee generally demands a Grade-Ia to Ib evidence. As long as the actual evidence of prophylaxis in adult haemophiliacs does not meet the postulated criteria of the German Federal Joint Committee, prophylactic replacement therapy of the individual case has to be well documented and reasonably explained. PMID- 22057947 TI - Comparison of three protocols for superovulation of brown brocket deer (Mazama gouazoubira). AB - This study aims to evaluate the ovulation rate and the presence of functional corpora lutea after treatment by three different protocols designed to cause superovulation in brown brocket deer. Six female received an intravaginal device containing 0.33 g of progesterone (CIDR(r)) for 8 days, followed by 0.5 mg injection of estradiol benzoate at the time of insertion and 265 ug of cloprostenol at the time of removal. Afterwards, the hinds were divided into three groups (n = 2): Treatment A received injection of 600 IU eCG on Day 4 after CIDR(r) insertion; Treatment B received injection of 300 IU eCG at the same time; and Treatment C received injection of 250 IU FSH dissolved in PVP, also on Day 4 post-insertion. The treatments were crossed over with 44-48 day intervals after CIDR(r) removal, such that all the deer were submitted to all three treatments. The mean ovulation rate (Treatment A = 3.40 +/- 0.68, Treatment B = 1.40 +/- 0.24, Treatment C = 0.80 +/- 0.49), total ovarian stimulation (Treatment A = 4.80 +/- 1.02, Treatment B = 1.80 +/- 0.37, Treatment C = 1.40 +/- 0.60), and mean CL diameter (Treatment A = 7.33 +/- 0.76 mm, Treatment B = 3.94 +/- 0.19 mm, Treatment C = 2.18 +/- 0.49 mm) in Treatment A were significantly higher than the mean ovulation rates, total ovarian stimulation, and mean CL diameter in Treatments B and C. The mean fecal progesterone metabolites at the luteal phase in Treatment A (6,277.94+/-2,232.47 ng/g feces) was significantly different from Treatment C (1,374.82+/-401.77 ng/g feces). Thus, although fertility was not evaluated directly, Treatment A proved capable of induce superovulation in the species Mazama gouazoubira, presenting the greatest mean ovulation rates, with the formation of functional corpora lutea. PMID- 22057948 TI - N-cadherin and M-cadherin are sequentially expressed in myoblast populations contributing to the first and second waves of myogenesis in the trout (Oncorhynchus mykiss). AB - The objective of this study was to investigate the expression of two promyogenic cell surface adhesion receptors, N- and M-cadherin, in developing trout (Oncorhynchus mykiss) somite, taking account of the recent identification of a dermomyotome-like epithelium in teleosts. In situ hybridization showed that N cadherin was expressed throughout the paraxial mesoderm and nascent somite. As the somite matured, N-cadherin expression disappeared ventrally from the sclerotome, and then mediolaterally from the differentiating slow and fast muscle cells of the embryonic myotome, to become finally restricted to the undifferentiated myogenic precursors forming the dermomyotome-like epithelium that surrounds the embryonic myotome. By contrast, M-cadherin, which was transcribed in the differentiating embryonic myotome, was never expressed in the dermomyotome-like epithelium. In late-stage trout embryos, M-cadherin transcript was only detected at the periphery of the expanding myotome, where muscle cells stemming from the N-cadherin positive dermomyotome-like epithelium differentiate. Collectively, our results support the view that, in trout embryo, N-cadherin is associated with muscle cell immaturity while M-cadherin is associated with muscle cell maturation and differentiation and this during the two successive phases of myogenesis. PMID- 22057949 TI - Optimization production of acid urease by Enterobacter sp. in an approach to reduce urea in Chinese rice wine. AB - Urea in alcoholic beverages is a precursor of ethyl carbamate, which is carcinogenic. Acid urease (EC 3.5.1.5) is regarded as a good approach to scavenge the urea. The acid urease of Enterobacter sp. R-SYB082, with lower optimum pH than the widely used commercial acid urease, exhibited a urea removal rate of 66.5% in Chinese rice wine, which was higher than that of the commercial acid urease (58.9%). The production of the acid urease was optimized from 1,100 to 2,504 U L(-1) by an approach which includes the optimization of initial glucose concentration, the elevation of anaerobic level of the reactor by charging CO(2) and in vitro natural activation of the target enzyme by simple cold storage (4 degrees C). These would open up the possibility for developing industrial application of this acid urease for producing high-quality Chinese rice wine. PMID- 22057950 TI - Selecting against antibiotic-resistant pathogens: optimal treatments in the presence of commensal bacteria. AB - Using optimal control theory as the basic theoretical tool, we investigate the efficacy of different antibiotic treatment protocols in the most exacting of circumstances, described as follows. Viewing a continuous culture device as a proxy for a much more complex host organism, we first inoculate the device with a single bacterial species and deem this the 'commensal' bacterium of our host. We then force the commensal to compete for a single carbon source with a rapidly evolving and fitter 'pathogenic bacterium', the latter so-named because we wish to use a bacteriostatic antibiotic to drive the pathogen toward low population densities. Constructing a mathematical model to mimic the biology, we do so in such a way that the commensal would be eventually excluded by the pathogen if no antibiotic treatment were given to the host or if the antibiotic were over deployed. Indeed, in our model, all fixed-dose antibiotic treatment regimens will lead to the eventual loss of the commensal from the host proxy. Despite the obvious gravity of the situation for the commensal bacterium, we show by example that it is possible to design drug deployment protocols that support the commensal and reduce the pathogen load. This may be achieved by appropriately fluctuating the concentration of drug in the environment; a result that is to be anticipated from the theory optimal control where bang-bang solutions may be interpreted as intermittent periods of either maximal and minimal drug deployment. While such 'antibiotic pulsing' is near-optimal for a wide range of treatment objectives, we also use this model to evaluate the efficacy of different antibiotic usage strategies to show that dynamically changing antimicrobial therapies may be effective in clearing a bacterial infection even when every 'static monotherapy' fails. PMID- 22057951 TI - Response to "blood levels of methemoglobin in patients with aluminum phosphide poisoning and its correlation with patient's outcome". PMID- 22057952 TI - A novel marine silk. AB - The discovery of a novel silk production system in a marine amphipod provides insights into the wider potential of natural silks. The tube-building corophioid amphipod Crassicorophium bonellii produces from its legs fibrous, adhesive underwater threads that combine barnacle cement biology with aspects of spider silk thread extrusion spinning. We characterised the filamentous silk as a mixture of mucopolysaccharides and protein deriving from glands representing two distinct types. The carbohydrate and protein silk secretion is dominated by complex beta-sheet structures and a high content of charged amino acid residues. The filamentous secretion product exits the gland through a pore near the tip of the secretory leg after having moved through a duct, which subdivides into several small ductules all terminating in a spindle-shaped chamber. This chamber communicates with the exterior and may be considered the silk reservoir and processing/mixing space, in which the silk is mechanically and potentially chemically altered and becomes fibrous. We assert that further study of this probably independently evolved, marine arthropod silk processing and secretion system can provide not only important insights into the more complex arachnid and insect silks but also into crustacean adhesion cements. PMID- 22057953 TI - Predictive value of preoperative electrocardiography for perioperative cardiovascular outcomes in patients undergoing noncardiac, nonvascular surgery. AB - BACKGROUND: The utility of routine preoperative electrocardiography (ECG) for assessing perioperative cardiovascular risk in patients undergoing noncardiac, nonvascular surgery (NCNVS) is unclear. HYPOTHESIS: There would be an association between preoperative ECG and perioperative cardiovascular outcomes in patients undergoing NCNVS. METHODS: A total of 660 patients undergoing NCNVS were prospectively evaluated. Patients age >18 years who underwent an elective, nonday case, open surgical procedure were enrolled. Troponin I concentrations and 12 lead ECG were evaluated the day before surgery, immediately after surgery, and on the first 5 postoperative days. Preoperative ECG showing atrial fibrillation, left or right bundle branch block, left ventricular hypertrophy, frequent premature ventricular complexes, pacemaker rhythm, Q-wave, ST-segment changes, or sinus tachycardia or bradycardia were classified as abnormal. The patients were followed up during hospitalization and were evaluated for the presence of perioperative cardiovascular events (PCE). RESULTS: Eighty patients (12.1%) experienced PCE. Patients with abnormal ECG findings had a greater incidence of PCE than those with normal ECG results (16% vs 6.4%; P < 0.001). Mean QTc interval was significantly longer in the patients who had PCE (436.6 +/- 31.4 vs 413.3 +/- 16.7 ms; P < 0.001). Univariate analysis showed a significant association between preoperative atrial fibrillation, pacemaker rhythm, ST segment changes, QTc prolongation, and in-hospital PCE. However, only QTc prolongation (odds ratio: 1.15, 95% confidence interval: 1.06-1.2, P < 0.001) was an independent predictor of PCE according to the multivariate analysis. Every 10 ms increase in QTc interval was related to a 13% increase for PCE. CONCLUSIONS: Prolongation of the QTc interval on the preoperative ECG was related with PCE in patients undergoing NCNVS. PMID- 22057954 TI - Cervical abscess in an immunocompetent patient with Mycobacterium malmoense pulmonary disease. AB - BACKGROUND: Mycobacterium malmoense is a nontuberculous mycobacteria seen mainly in two age groups and with different clinical presentations. Most patients are male adults presenting clinical symptoms and signs similar to those of pulmonary tuberculosis. The second group is formed by immunocompetent children with localized cervical lymphadenitis. Although cervical adenitis is the main extrapulmonary manifestation of M. malmoense, virtually all cases of cervical disease were documented in children. Disseminated disease is rare and has been reported in patients with severely impaired immunity. CASE REPORT: We report a case of a 47-year-old immunocompetent man with a cervical abscess, in whom we identified a M. malmoense pulmonary disease with multiple cervical, thoracic and abdominal adenopathies. CONCLUSION: Extrapulmonary infection due to M. Malmoense needs to be considered on the differential diagnosis of cervical masses and adenopathies, not only in pediatric patients but also in adults with no impaired immunity. A high index of suspicion for nontuberculous mycobacteria is essential for the diagnosis and prognosis. PMID- 22057955 TI - Use of molecular markers in reciprocal recurrent selection of maize increases heterosis effects. AB - We examined the effect of incorporation of molecular markers on variability between and within populations in order to maximize heterotic effects and longevity of a maize reciprocal recurrent selection program. Molecular variability was quantified by inter-simple sequence repeat (ISSR) markers between and within the maize populations Cimmyt and Piranao in the 10th cycle of a reciprocal recurrent selection program. Forty-two S(1) progenies of each population were analyzed, these being families of full-sibs selected according to their agronomic traits. Thirteen primers were selected, which produced 140 bands; 114 of them were polymorphic and 26 monomorphic. Based on UPGMA grouping analysis and by genetic distances, it was possible to identify "contaminant" progenies. These progenies belong to the Piranao or Cimmyt groups, but cluster in the opposite heterotic group. Identification of "contaminant" progenies is relevant for selection, because, besides identifying genotypes that should be eliminated at the recombination stage, it allows increased heterosis expression in crosses between more genetically distinct individuals. After the elimination of the "contaminant" progenies and those that were allocated between the heterotic groups, a new statistical analysis was carried out, which demonstrated increased genetic distances between the populations. It was concluded that the application of molecular markers in reciprocal recurrent selection programs allows the optimization of the monitoring of genetic variability within and between populations, favoring recombination between more distant progenies, besides ensuring increased longevity of the reciprocal recurrent selection program. PMID- 22057956 TI - A66G and C524T polymorphisms of the methionine synthase reductase gene are associated with congenital heart defects in the Chinese Han population. AB - Congenital heart defects (CHDs) are the most common birth defects; genes involved in homocysteine/folate metabolism may play important roles in CHDs. Methionine synthase reductase (MTRR) is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine. We investigated whether two polymorphisms (A66G and C524T) of the MTRR gene are associated with CHDs. A total of 599 children with CHDs and 672 healthy children were included; the polymorphisms were detected by PCR and RFLP analysis. Significant differences in the distributions of A66G and C524T alleles were observed between CHD cases and controls, and slightly increased risks of CHD were associated with 66GG and 524CT genotypes (odds ratios = 1.545 and 1.419, respectively). The genotype frequencies of 524CT in the VSD subgroup, 66GG and 524CT in the PDA subgroup were significantly different from those of controls. In addition, the combined 66AA/524CT, 66AG/524CT and 66GG/524CT in CHDs had odds ratios = 1.589, 1.422 and 1.934, respectively. Increased risks were also observed in 66AA/524CT and 66GG/524CT for ASD, 66AG/524CT for VSD, as well as 66GG/524CT for PDA. In conclusion, MTRR A66G and C524T polymorphisms are associated with increased risk of CHDs. PMID- 22057957 TI - Two genetic stocks of Steindachneridion melanodermatum living in sympatry in nature and genetic variability of wild parents and F1 generation. AB - Steindachneridion melanodermatum is a large Brazilian catfish, highly prized for sport fishing and for its meat. Specimens of this species, both caught in nature from Iguacu River and F(1) fish born in captivity, were analyzed with regard to patterns of RAPD molecular markers. Genetic similarity ranged from 0.57 to 0.95; two groups were determined for the wild specimens. The results suggest different genetic lineages in sympatry in nature. Heterozygosity and percentage of polymorphic loci were 0.31 and 79% and 0.23 and 62%, respectively, for the two populations of wild specimens and 0.26 and 66%, respectively, for those born in captivity. PMID- 22057958 TI - Genome-wide identification, phylogeny and expression analysis of the lipoxygenase gene family in cucumber. AB - Plant lipoxygenase (LOX) is involved in growth and developmental control processes, through the biosynthesis of regulatory molecules and defense responses to pathogens, wounding and stress. To date, few LOX proteins and little tissue expression profiling have been reported in detail for cucumber (Cucumis sativus L.). Recent completion of the cucumber genome sequence now permits genome-wide analysis of the LOX gene family in cucumber as well as comparison with LOX in Arabidopsis and rice. We identified 23 candidate LOX genes in the cucumber genome; phylogenetic analysis indicated that these LOX members cluster into two groups, designated types 1 and 2, as expected from previous studies. Sequence analysis showed that five binding sites of iron, including two consensus histidines in the LOX domain, are highly conserved in the cucumber LOX proteins. Analysis of chromosomal localization and genome distribution suggested that tandem duplication and/or polyploidal duplication contributed to the expansion of the cucumber LOX gene family. Based on intron/exon structure analysis, only a few of the extant intron patterns existed in the ancestor of monocots and eudicots. Expression data showed widespread distribution of the cucumber LOX gene family within plant tissues, suggesting that they perform different functions in different tissues. PMID- 22057959 TI - Functional characterization and signal transduction ability of nucleotide-binding site-leucine-rich repeat resistance genes in plants. AB - Pathogen infection in plants is often limited by a multifaceted defense response triggered by resistance genes. The most prevalent class of resistance proteins includes those that contain a nucleotide-binding site-leucine-rich repeat (NBS LRR) domain. Over the past 15 years, more than 50 novel NBS-LRR class resistance genes have been isolated and characterized; they play a significant role in activating conserved defense-signaling networks. Recent molecular research on NBS-LRR resistance proteins and their signaling networks has the potential to broaden the use of resistance genes for disease control. Various transgenic approaches have been tested to broaden the disease resistance spectrum using NBS LRR genes. This review highlights the recent progress in understanding the structure, function, signal transduction ability of NBS-LRR resistance genes in different host-pathogen systems and suggests new strategies for engineering pathogen resistance in crop plants. PMID- 22057960 TI - Detection of fetal RHD pseudogene (RHDPsi) and hybrid RHD-CE-Ds from RHD-negative pregnant women with a free DNA fetal kit. AB - Hemolytic disease of the newborn is a clinical condition in which maternal and paternal Rh blood group antigens are incompatible and the mother is negative for the antigen whereas the father is positive. Analysis of fetal cells recovered from maternal plasma can provide a highly sensitive prenatal diagnosis. The fetal RHD gene in plasma DNA is detected by real-time PCR amplification of two different segments of the RHD gene (exons 7 and 10). Each amplicon is revealed with specific probes. We examined 40 female blood samples to verify the specificity of RHD exons (7 and 10) amplified by real-time PCR. Thirty fetuses were predicted to be RHD-positive based on analysis of plasma DNA. Seven fetuses were predicted to be RHD-negative. One fetus was negative for RHD on exon 10, and positive for RHD on exon 7 (early gestation age); two fetuses were RHD negative on exon 7, and RHD-positive on exon 10 (RHD-CE-D(s) or RHDPsi), indicative of a maternal RHD allele. We conclude that it is necessary to analyze at least two exon regions in the RHD gene. PMID- 22057961 TI - Using PCR for early diagnosis of bovine leukemia virus infection in some native cattle. AB - Bovine leukemia virus (BLV), the causative agent of enzootic bovine leukosis, is an exogenous, B lymphotropic retrovirus belonging to the Retroviridae family that induces persistent lymphocytosis in cattle and sheep. PCR has proven to be particularly suitable for investigating herds of cattle with a very low incidence of BLV infection and for clarifying doubtful serological results obtained by immunodiffusion or ELISA. The native Iranian and Russian cattle have a series of valuable traits that discriminate them as unique breeds that are well able to compete with western analogues. However, their gene pools have not been analyzed with molecular markers, including detection of BLV by PCR. Two pairs of primers were used: gag1 and gag2, and pol1 and pol2, which encompass 347- and 599-bp fragments of the BLV gene, respectively. Sixty-five Iranian Sistani, 120 Yaroslavl, 50 Mongolian, and 35 Black Pied cows were investigated. Among these 270 animals, we obtained 42 positive and 15 doubtful results in the first PCR. The second PCR was very effective in increasing BLV test reliability data to support detection of BLV. PMID- 22057962 TI - Smith-Magenis syndrome: clinical evaluation in seven Brazilian patients. AB - Smith-Magenis syndrome (SMS) is a complex congenital anomaly characterized by craniofacial anomalies, neurological and behavioral disorders. SMS is caused by a deletion in region 17p11.2, which includes the RAI1 gene (90% of cases), or by point mutation in the RAI1 gene (10% of cases). Laboratory diagnosis is through cytogenetic analysis by GTG banding and molecular cytogenetic analysis by FISH. We carried out an active search for patients in Associations of Parents and Friends of Exceptional Children (APAE) of Sao Paulo and genetic centers in Brazil. Forty-eight patients were screened for mental retardation, craniofacial abnormalities and stereotyped behavior with a diagnosis of SMS. In seven of them, chromosome banding at high resolution demonstrated chromosome 17p11.2 deletions, confirmed by FISH. We also made a meta-analysis of 165 cases reported between 1982 and 2010 to compare with the clinical data of our sample. We demonstrated differences between the frequencies of clinical signs among the cases reported and seven Brazilian cases of this study, such as dental anomalies, strabismus, ear infections, deep hoarse voice, hearing loss, and cardiac defects. Although the gold standard for diagnosis of SMS is FISH, we found that the GTG banding technique developed to evaluate chromosome 17 can be used for the SMS diagnosis in areas where the FISH technique is not available. PMID- 22057963 TI - Chemical synthesis and improved expression of recombinant human granulocyte colony-stimulating factor cDNA. AB - Recently, granulocyte colony-stimulating factor (G-CSF) has been recognized as a useful molecule for the treatment of a wide range of complex ailments, such as cancer, AIDS, H1N1 influenza, cardiac and neurological diseases. The vast therapeutic potential of G-CSF has induced scientists to develop biotechnological approaches for the synthesis of this pharmacologically active agent. We used a synthetic G-CSF cDNA molecule to produce the target protein by a simple cloning protocol. We constructed the synthetic cDNA using a DNA synthesizer with the aim to increase its expression level by specific sequence modifications at the 5' end of the G-CSF-coding region, decreasing the GC content without altering the predicted amino acid sequences. The identity of the resulting protein was confirmed by a highly specific enzyme-linked immunosorbent assay. In conclusion, a synthetic G-CSF cDNA in combination with the recombinant DNA protocol offers a rapid and reliable strategy for synthesizing the target protein. However, commercial utilization of this methodology will require rigorous validation and quality control. PMID- 22057964 TI - Microbial diversity in the larval gut of field and laboratory populations of the sugarcane weevil Sphenophorus levis (Coleoptera, Curculionidae). AB - The sugarcane weevil, Sphenophorus levis, is a wide-spread sugarcane pest in Brazil. Sphenophorus levis may depend on microorganisms that inhabit its intestinal tract. We examined the diversity of the gut microbiota of S. levis, which was characterized using culture-dependent and culture-independent methods. Analysis of 16S rRNA amplified directly from the gut community revealed the presence of 14 genera, one group from the Candidatus category, one uncultured group assigned to the family Flavobacteriaceae, and one uncultured group assigned to the family Enterobacteriaceae; all of them are members of the Alpha Proteobacteria, Beta-Proteobacteria, Gamma-Proteobacteria, Firmicutes, and Bacteroidetes phyla. Microorganisms isolated through culture-dependent methods were classified according to morphological parameters and by 16S rRNA gene sequences. In addition to bacteria, four filamentous fungi were isolated. A higher bacterial diversity was observed in field populations of larvae than in laboratory populations, according to the Shannon index (Field H' = 3.36; Laboratory H' = 3.26). Five genera of bacteria and two filamentous fungi were found to have cellulolytic activity. This is the first report of S. levis gut microbiota; it may contribute to development of strategies for controlling this sugarcane pest. PMID- 22057965 TI - Iron-catalyzed C-H and C-C bond cleavage: a direct approach to amides from simple hydrocarbons. AB - Something functional: The title reaction proceeds in the presence of azide and water to deliver amides in high yields, and it can be used in a ring-expansion strategy to generate lactams. A mechanism is proposed based on experimental results. This reaction offers a new approach to functionalizing simple and readily available hydrocarbons. DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. PMID- 22057966 TI - Endocrine changes after pediatric traumatic brain injury. AB - Traumatic brain injury (TBI) is a very common occurrence in childhood, and can lead to devastating long term consequences. Recent research has focused on the potential endocrine consequences of TBI in adults. The research in children is less robust. This paper reviews current literature regarding TBI and possible hypothalamic and pituitary deficiencies in childhood. Acute endocrine changes are commonly found after TBI in pediatric patients, which can include changes in hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release. In the long term, both temporary and permanent alterations in pituitary function have been found. About 30% of children have hypopituitarism up to 5 years after injury. Growth hormone deficiency and disturbances in puberty are the most common, but children can also experience ACTH deficiency, diabetes insipidus, central hypothyroidism, and elevated prolactin. Every hormonal axis can be affected after TBI in children, although growth hormone deficiency and alterations in puberty are the most common. Because transient and permanent hypopituitarism is common after TBI, survivors should be screened serially for possible endocrine disturbances. These children should undergo routine surveillance at least 1 year after injury to ensure early detection of deficiencies in hormonal production in order to permit normal growth and development. PMID- 22057967 TI - ACTH-secreting pituitary adenomas: size does not correlate with hormonal activity. AB - ACTH-secreting pituitary adenomas (Cushing's disease, CD) are the most frequent cause of Cushing's syndrome. To test whether the size of ACTH-secreting adenomas correlates with the degree of biochemical and clinical features of hypercortisolism, we retrospectively reviewed all newly diagnosed CD patients seen at our institution by two neuro-endocrinologists over a 10-year time period. We documented the number of clinical manifestations and baseline hormonal measurements. There were 37 microadenomas (MUAs) and 16 macroadenomas (MAs). We sought to characterize the relationship between tumor size (MUA vs. MA) and number of signs and symptoms of hypercortisolism and biochemical assessment of hypercortisolemia. There were no significant differences in mean age, BMI, or prevalence of hypertension and type 2 diabetes between the MUA and MA groups. However, the MAs had fewer clinical manifestations of hypercortisolism (29.4% vs. 36.1%, P = 0.02) compared to MUAs. There was a higher prevalence of easy bruisability and proximal muscle weakness in the MUAs, but otherwise the prevalence of signs and symptoms were similar between groups. The MAs had a lower random serum cortisol (18.2 +/- 2.4 vs. 25.9 +/- 1.8 mcg/dl, P = 0.018), lower cortisol:ACTH ratio (0.25 +/- 0.03 vs. 0.42 +/- 0.05, P < 0.048), and lower cortisol:tumor diameter ratio (14.1 +/- 2.2 vs. 56.8 +/- 7.2, P < 0.0001) than the MUAs. We conclude that tumor size does not directly correlate with the extent of hormonal activity in ACTH-secreting adenomas. Biochemical activity and clinical manifestations may be mild even in larger tumors, and therefore a high index of suspicion may be necessary to recognize hypercortisolism in pituitary MAs. PMID- 22057968 TI - Synthesis and characterization of hydrolytically degradable copolyester biomaterials based on glycolic acid, sebacic acid and ethylene glycol. AB - Copolyesters of glycolic acid (G) combined with sebacic acid (S) and ethylene glycol were synthesized in different molar ratios (G: 0-100% and S: 100-0%) and their hydrolytic degradation was studied and correlated with their structures. Based on the FTIR spectra of the homopolyesters and copolyesters and the normalized peak intensity of the I(2918), I(2848) and I(1087) for the corresponding wavenumbers, it is concluded that the I(2918) and the I(2848) are in accordance with the mean number degree of polymerization of ethylene sebacate units and the I(1087) is in accordance with the mean number degree of polymerization of glycolate units. Based on the XRD diffractograms, poly(ethylene sebacate) and poly(glycolic acid) belong to the monoclinic and the orthorhombic crystal system, respectively and both have higher crystallinity than the copolyesters. The experimental data of the hydrolytic degradation were fitted with exponential rise to maximum type functions using two-parameter model and four-parameter model. Three regions can been distinguished for the hydrolytic degradation by decreasing the molar feed ratio of sebacic acid, which are correlated with the changes of crystallinity. Two copolyesters are proposed: first the copolyester with high amount of glycolate units (S10G90) having higher hydrolytic degradation than G100 and second the copolyester with equal amount of glycolate and ethylene sebacate units (S50G50), having lower hydrolytic degradation than G100. These hydrolytically degradable copolyesters are soluble in common organic solvents, opposite to poly(glycolic acid) and could have perspectives for biomedical applications. PMID- 22057969 TI - A shape memory stent of poly(epsilon-caprolactone-co-DL-lactide) copolymer for potential treatment of esophageal stenosis. AB - Biodegradable polymer stent with shape memory effect is expected to be developed in the treatment of esophageal stenosis, most likely due to traditional stents having such shortages as considerable rigidity and nondegradation. A tubular stent with the inner and outer diameters of 28 and 30 mm was manufactured from biodegradable poly(epsilon-caprolactone-co-DL-lactide) (PCLA) copolymer consisting of epsilon-caprolactone and DL-lactide at a weight ratio of 10/90. A series of tests were accomplished to investigate its properties including shape memory effects (SMEs), compression property and influence of in vitro degradation of polymer matrix on its shape recovery and dilation force. Significantly, an implantation of the stent into a dog model was performed to evaluate its function for the treatment of esophageal stenosis. The deformed stent needs about 36 s to recover its initial shape in vitro in 37 degrees C warm water. The primary animal experiment in vivo has revealed that the implanted deformed stent could be triggered by body temperature and expectedly returned to a nearly-round shape to support esophageal wall. Therefore, the biodegradable intelligent polymer stent may be great potential to displace the conventional metallic stents for the esophageal stenosis therapy. PMID- 22057970 TI - Human platelet rich plasma plus Persian Gulf coral effects on experimental bone healing in rabbit model: radiological, histological, macroscopical and biomechanical evaluation. AB - Coral is an osteoconductive material used as a bone graft extender and human platelet rich plasma has been used as a source of osteoinductive factor. A combination of human platelet rich plasma and coral is expected to create a composite with both osteoconductive and osteoinductive properties. This study examined the effect of a combination of human platelet rich plasma and coral on osteogenesis in vivo using rabbit model of bone healing. A critical size defect of 10 mm elongation was created in the radial diaphysis of 36 rabbit and either supplied with coral-human PRP, or coral alone or left empty (control group). The platelets in the PRP were about 10.1 fold compared to normal blood. Radiographs of each forelimb was taken postoperatively on 1st day and then at the 2nd, 4th, 6th and 8th weeks post injury to evaluate bone formation, union and remodeling of the defect. The operated radiuses were removed on 56th postoperative day and were grossly and histopathologically evaluated. In addition, biomechanical test was conducted on the operated and normal forearms of the rabbits. This study demonstrated that coral-human PRP (hPRP), could promote bone regeneration in critical size defects with a high regenerative capacity. The results of the present study demonstrated that coral-hPRP could be an attractive alternative for reconstruction of the major diaphyseal defects of the long bones in animal models. PMID- 22057971 TI - Real time analysis of protein location and function: a Golgi-specific PKD sensor. PMID- 22057972 TI - High level of miR-21, miR-10b, and miR-31 expression in bilateral vs. unilateral breast carcinomas. AB - We analyzed the expression of several microRNAs (miRs) implicated in breast cancer (BC) pathogenesis (miR-21, miR-10b, miR17-5p, mir-31, miR-155, miR-200c, miR-18a, miR-205, and miR-27a) in 80 breast carcinomas obtained from patients with bilateral BC (biBC) and 40 cases of unilateral BC (uBC). Unexpectedly, three miRs (miR-21, miR-10b and miR-31) demonstrated significantly higher level of expression in biBC vs. uBC (P = 0.0001, 0.00004 and 0.0002, respectively). Increased contents of miR-21, miR-10b and miR-31 were observed in all categories of biBC tumors, i.e., in synchronous biBC as well as in first and second tumors from metachronous biBC cases. Synchronous biBC showed more similarity of miR expression profiles within pairs that the metachronous doublets (P = 0.004). This study suggests that bilateral breast tumors have somewhat distinct pattern of molecular events as compared to the unilateral disease. PMID- 22057973 TI - Role of interleukin-10 in breast cancer. AB - Cytokines are low molecular weight regulatory proteins or glycoprotein that modulates the intensity and duration of immune response by stimulating or inhibiting the activation, proliferation, and/or differentiation of target cells. Different cytokines are known to have diverse role in breast cancer initiation and progression. Interleukin-10 (IL-10), a pleiotropic anti-inflammatory cytokine, induces immunosuppression and assists in escape from tumor immune surveillance. Like several other cytokines, IL-10 also can exert dual proliferative and inhibitory effect on breast tumor cells indicating a complex role of IL-10 in breast cancer initiation and progression. In this review, we tried to put together a comprehensive current view on significance of IL-10 in promotion, inhibition, and importance as prognosticator in breast cancer based on in vitro, in vivo, and clinical evidences. For literature collection, we conducted PubMed search with keywords "IL-10" and "breast cancer". PMID- 22057974 TI - Ultrasonographic differentiation of malignant from benign breast lesions: a meta analytic comparison of elasticity and BIRADS scoring. AB - There has been controversy regarding the accuracy of breast ultrasound elastography (USE) compared to conventional B-mode Ultrasound (USB). The purpose of this study was to conduct a direct comparative effectiveness analysis of USB versus USE or their combination in differentiating breast lesions through systematically reviewing recent literature. An extensive literature search of PubMed and other medical and general purpose databases from inception through August 2011 was conducted. Published studies that reported a direct comparison of the diagnostic performance of USE, using elasticity score versus USB, using breast imaging reporting and data system (BIRADS) for characterization of focal breast lesions were included. Summary diagnostic performance measures were assessed for each of the tests and their combination using bivariate generalized linear mixed modeling. The two tests were combined as: (1) conjunctive, where the outcome of the combination of tests is positive only if both test results are positive; (2) disjunctive, where the outcome of a combination of tests is negative only if both tests are negative. Twenty nine studies provided relevant information on 5,511 breast masses (2,065 cancers, 3,446 benign lesions). Sensitivity of USB, USE, and their conjunctive and disjunctive combinations were 96% (95% credible interval (CrI), 93-98%), 79% (95% CrI, 74-83%), 73% (95% CrI, 67-78%), and 99% (95% CrI, 98-99%), respectively. Specificity of USB, USE, and their conjunctive and disjunctive combinations were 70% (95% CrI, 55-83%), 88% (95% CrI, 82-92%), 97% (95% CrI, 95-99%), and 56% (95% CrI, 43-69%), respectively. The application of USE as a single test is not superior to USB alone. However, in low risk patients it is recommended to perform an USE following a positive USB result to decrease the rate of unnecessary biopsies. PMID- 22057977 TI - Chief resident year as stepping stone to attending academic hospitalist. PMID- 22057975 TI - Assessing anxious features in depressed outpatients. AB - Both the 17-item Hamilton Rating Scale for Depression (HRSD(17)) and 30-item Inventory of Depressive Symptomatology - Clinician-rated (IDS-C(30) ) contain a subscale that assesses anxious symptoms. We used classical test theory and item response theory methods to assess and compare the psychometric properties of the two anxiety subscales (HRSD(ANX) and IDS-C(ANX)) in a large sample (N = 3453) of outpatients with non-psychotic major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Approximately 48% of evaluable participants had at least one concurrent anxiety disorder by the self report Psychiatric Diagnostic Screening Questionnaire (PDSQ). The HRSD(ANX) and IDS-C(ANX) were highly correlated (r = 0.75) and both had moderate internal consistency given their limited number of items (HRSD(ANX) Cronbach's alpha = 0.48; IDS-C(ANX) Cronbach's alpha = 0.58). The optimal threshold for ascribing the presence/absence of anxious features was found at a total score of eight or nine for the HRSD(ANX) and seven or eight for the IDS-C(ANX) . It would seem beneficial to delete item 17 (loss of insight) from the HRSD(ANX) as it negatively correlated with the scale's total score. Both the HRSD(ANX) and IDS C(ANX) subscales have acceptable psychometric properties and can be used to identify anxious features for clinical or research purposes. PMID- 22057978 TI - Inhibition of sodium current by taurine magnesium coordination compound prevents cesium chloride-induced arrhythmias. AB - The mechanism(s) by which taurine magnesium coordination compound (TMCC) inhibits experimental arrhythmias remains poorly understood. The purpose of this study was to observe the effects of TMCC against cesium chloride-induced arrhythmia in the rabbit heart and find whether the antiarrhythmic activity is related to inhibition of sodium current. Early afterdepolarization was induced by 1.5 mM cesium chloride (1 ml kg(-1)) through intravenous injection. The monophasic action potentials (MAP) and electrocardiograms were simultaneously recorded. The effect of TMCC on functional refractory periods (FRPs) in the left atrium was also observed in vitro. Arrhythmias onset was significantly retarded by TMCC. The number of ventricular premature contractions and incidence of monophasic ventricular tachycardia and polyphasic ventricular tachycardia in 10 min were decreased by TMCC. These effects can be abolished by veratridine (10 MUg kg(-1)). MAP duration at 90% repolarization was significantly prolonged by TMCC, which can be prolonged even longer by veratridine (10 MUg kg(-1)). In vitro experiments showed that FRPs was prolonged by TMCC which can be cancelled by veratridine (10 MUg kg(-1)). TMCC prevents cesium chloride-induced arrhythmias, and inhibition of sodium current, in part, contributes to the antiarrhythmic effect of TMCC. PMID- 22057979 TI - Myofibroblast cells are preferentially expressed early in a rabbit model of joint contracture. AB - Studies have demonstrated increased myofibroblasts in contractures. However, the timeline is largely unknown. The aim of this study was to determine the number of myofibroblasts in contracting joint capsules at 3-time points over a 24-week period. Eighteen rabbits subjected to a surgical procedure designed to elicit a knee joint contracture were divided into three groups of six. Rabbits were sacrificed at each respective time point and myofibroblasts in the joint capsules were quantified using immunohistochemistry. The percent of myofibroblasts was significantly elevated in the operated limbs compared to the control limbs at 2 weeks (20% vs. 7%, respectively; p = 0.014). There was no difference in the percent of myofibroblasts between the operated and control limbs at 8 or 24 weeks (p = 0.96 and 0.07, respectively). The percent of myofibroblasts dropped from 20% at 2 weeks to 3.0% at 8 weeks (p < 0.001). The decrease from 8 to 24 weeks was not significant (p = 0.19). A large proportion of myofibroblasts are present in contracted joints at 2 weeks. By week 8, the proportion of myofibroblasts seem to return to normal. Interventions aimed at affecting the myofibroblast cell in order to prevent fibrosis should be instituted early. PMID- 22057980 TI - Infantile midaortic syndrome with aortic occlusion. AB - Mid aortic syndrome (MAS) is a rare condition often presenting with severe hypertension. It is characterized by narrowing of the abdominal aorta. We here describe a case of complete occlusion of the abdominal aorta presenting in infancy. This child presented at four months of age with heart failure and hypertension. CT angiogram showed total narrowing of the abdominal aorta. This was initially felt to be too severe for surgical treatment and he was planned for palliative care. We were however able to improve his blood pressure with antihypertensive agents and he underwent succesful angioplasty at five and a half months of age. He has required three further angioplasty procedures and still needs two antihypertensive agents to control his blood pressure. His renal function remains normal and at age six years he has excellent quality of life with normal growth and development. This case illustrates that the combination of medical treatment and angioplasty can give an excellent long-term treatment response even in children with extremely severe MAS. This boy now has normal blood pressure and has experienced normal growth, development and quality of life. PMID- 22057981 TI - Urinary N-acetyl-beta-D glucosaminidase (NAG) level in idiopathic nephrotic syndrome. AB - Urinary N-acetyl-beta-D: glucosaminidase (NAG) is a sensitive biomarker of renal parenchymal disease. The aim of this study was to investigate variations in the levels of NAG excretion among different sub-groups of nephrotic syndrome (first episode, relapsers, and resistant) and its prediction based on proteinuria. Thirty-five patients with idiopathic nephrotic syndrome, aged 1-12 years, as well as 15 age- and gender-matched normal children (controls) were enrolled in the study. Among the 35 patients, ten were classified with first episode nephrotic syndrome (FENS), 17 with relapsing nephrotic syndrome (RNS), and eight with steroid-resistant nephrotic syndrome (SRNS). Urinary NAG/creatinine levels were significantly increased in SRNS patients as compared to FENS and RNS patients (p < 0.001); the FENS and RNS groups had comparable levels. A urinary NAG/creatinine value of <=108.9 U/g was found to identify steroid-sensitive patients with a sensitivity, specificity, positive predictive value, and negative predictive value of 78.8, 100, 100 and 77.7%, respectively. Significant correlations were found between experimental and predicted values of urinary NAG/creatinine in steroid sensitive nephrotic syndrome (SSNS) (R (2) = 0.9643) and SRNS patients (R (2) = 0.9823). Urinary NAG/creatinine values were found to be higher in SRNS than SSNS patients and have moderate predictive value for steroid responsiveness. This level can be obtained based on urinary protein/creatinine ratio or 24 h urinary protein levels. PMID- 22057983 TI - Phonological awareness, reading skills, and vocabulary knowledge in children who use cochlear implants. AB - In hearing children, reading skills have been found to be closely related to phonological awareness. We used several standardized tests to investigate the reading and phonological awareness skills of 27 deaf school-age children who were experienced cochlear implant users. Approximately two-thirds of the children performed at or above the level of their hearing peers on the phonological awareness and reading tasks. Reading scores were found to be strongly correlated with measures of phonological awareness. These correlations remained the same when we statistically controlled for potentially confounding demographic variables such as age at testing and speech perception skills. However, these correlations decreased even after we statistically controlled for vocabulary size. This finding suggests that lexicon size is a mediating factor in the relationship between the children's phonological awareness and reading skills, a finding that has also been reported for typically developing hearing children. PMID- 22057984 TI - Contribution of a contralateral hearing aid to perception of consonant voicing, intonation, and emotional state in adult cochlear implantees. AB - Binaural hearing in cochlear implant (CI) users can be achieved either by bilateral implantation or bimodally with a contralateral hearing aid (HA). Binaural-bimodal hearing has the advantage of complementing the high-frequency electric information from the CI by low-frequency acoustic information from the HA. We examined the contribution of a contralateral HA in 25 adult implantees to their perception of fundamental frequency-cued speech characteristics (initial consonant voicing, intonation, and emotions). Testing with CI alone, HA alone, and bimodal hearing showed that all three characteristics were best perceived under the bimodal condition. Significant differences were recorded between bimodal and HA conditions in the initial voicing test, between bimodal and CI conditions in the intonation test, and between both bimodal and CI conditions and between bimodal and HA conditions in the emotion-in-speech test. These findings confirmed that such binaural-bimodal hearing enhances perception of these speech characteristics and suggest that implantees with residual hearing in the contralateral ear may benefit from a HA in that ear. PMID- 22057985 TI - Public and professional educational needs for downstaging breast cancer in Egypt. AB - We conducted focus groups with women from urban and rural areas in the Nile Delta region to investigate their attitudes regarding breast cancer diagnosis, treatment, and screening. Six 60-min focus groups, each group comprised of 6-10 women with ages between 20-69 years, were conducted. Discussions included breast health, breast cancer diagnosis, treatment, early detection and screening, and communication for breast health. Almost all urban and rural women reported that women do not see physicians until they are seriously ill or have advanced cancer. They reported that oncologists or gynecologists were important to be seen first if a woman suspected breast cancer and primary care physician are not the primary line of cancer diagnosis. Other deterring factors besides distrust in primary care physicians included attitude that breast cancer equals death and lack of knowledge of early detection and screening techniques. Women felt that public education campaigns must be implemented to improve early detection and screening methods for breast cancer. The majority of beliefs regarding breast cancer and screening were common among urban and rural women. Culture-specific and tailored professional and public education programs in developing countries are essential for achieving downstaging cancer. PMID- 22057986 TI - A DVD program on fall prevention skills training for cancer family caregivers. AB - This feasibility study tested an instructional DVD program for improving cancer family caregivers' knowledge and preparedness in fall prevention and reducing fall occurrence among the patients they care for at home. DVD program features included training caregivers on safe mobility skills. Family caregivers of cancer patients were surveyed before and after viewing the DVD program on "Moving Safely" in the home. Cancer patients were followed 4 months postintervention to determine if fall occurrence was reduced. There was a decrease in the number of patients who fell postintervention compared with those who fell preintervention. Caregivers' perceptions of knowledge about fall prevention improved significantly after viewing the DVD. An instructional DVD program is an effective educational tool for preparing family caregivers with the knowledge and skills needed to reduce the incidence of falls in the home setting. Educators must develop programs for preparing family caregivers to perform nursing skills within the home. PMID- 22057987 TI - Arabidopsis TTR1 causes LRR-dependent lethal systemic necrosis, rather than systemic acquired resistance, to Tobacco ringspot virus. AB - Most Arabidopsis ecotypes display tolerance to the Tobacco ringspot virus (TRSV), but a subset of Arabidopsis ecotypes, including Estland (Est), develop lethal systemic necrosis (LSN), which differs from the localized hypersensitive responses (HRs) or systemic acquired resistance (SAR) characteristic of incompatible reactions. Neither viral replication nor the systemic movement of TRSV was restricted in tolerant or sensitive Arabidopsis ecotypes; therefore, the LSN phenotype shown in the sensitive ecotypes might not be due to viral accumulation. In the present study, we identified the Est TTR1 gene (tolerance to Tobacco ringspot virus 1) encoding a TIR-NBS-LRR protein that controls the ecotype-dependent tolerant/sensitive phenotypes by a map-based cloning method. The tolerant Col-0 ecotype Arabidopsis transformed with the sensitive Est TTR1 allele developed an LSN phenotype upon TRSV infection, suggesting that the Est TTR1 allele is dominant over the tolerant ttr1 allele of Col-0. Multiple sequence alignments of 10 tolerant ecotypes from those of eight sensitive ecotypes showed that 10 LRR amino acid polymorphisms were consistently distributed across the TTR1/ttr1 alleles. Site-directed mutagenesis of these amino acids in the LRR region revealed that two sites, L956S and K1124Q, completely abolished the LSN phenotype. VIGS study revealed that TTR1 is dependent on SGT1, rather than EDS1. The LSN phenotype by TTR1 was shown to be transferred to Nicotiana benthamiana, demonstrating functional conservation of TTR1 across plant families, which are involved in SGT-dependent defense responses, rather than EDS1-dependent signaling pathways. PMID- 22057988 TI - Regulation of cotton fiber elongation by xyloglucan endotransglycosylase/hydrolase genes. AB - Ligon lintless mutant (li1li1) with super-short fibers (5-8 mm in length) and its wild type (Li1Li1) with normal fibers (30 mm in length) were used to study the function of xyloglucan endotransglycosylase/hydrolase (XTH) genes during fiber elongation in cotton. Wild-type cotton attained the fiber elongation stage earlier (5 days post-anthesis, DPA), than the Ligon lintless mutant (12 DPA) with a higher fiber elongation velocity of about 1.76 mm/day. Xyloglucan contents in Ligon lintless mutant fibers were 5-fold higher than the wild type during 9-15 DPA. It was also observed that the activity of XTH in wild-type cotton fibers was about 2-fold higher than that of the Ligon lintless mutant with a peak at 12 DPA. DNA blot analysis indicated that the XTH gene in the Ligon lintless mutant and its wild type belonged to a multiple allelic series. However, RNA blot analysis and quantitative real-time PCR exhibited an earlier expression (10 DPA) of XTH in wild type as compared to delayed (15 DPA) expression in the Ligon lintless mutant. The study also revealed that 9-15 DPA might be a key phase for upregulation of fiber elongation via increasing XTH activity. Higher XTH activity can cleave down the xyloglucan-cellulose chains thus loosening fiber cell wall and promoting fiber cell elongation in wild type as compared to its mutant. PMID- 22057989 TI - Association between matrix metalloproteinase-3 polymorphism and anterior cruciate ligament ruptures. AB - Anterior cruciate ligament (ACL) ruptures are considered to be the most severe joint injury in sports. However, the precise etiologies of ACL injuries are not fully understood. Recently, the gene encoding the matrix metalloproteinase-3 (MMP-3, stromelysin-1) was shown to be associated with anterior cruciate ligament ruptures. The 5A/6A polymorphism in the promoter of the MMP-3 gene affects the regulation of MMP-3 gene expression. We examined the association between polymorphism within -1612 of the MMP-3 gene and ACL rupture in an independent population. Eighty-six participants between 20 and 40 years of age with surgically diagnosed ACL ruptures and 100 healthy controls between 18 and 28 years of age without history of ligament or tendon injuries were recruited for the study. All participants were genotyped for the MMP-3 polymorphism (-1612 5A/6A). Statistical analyses of genotype frequencies between patients and healthy controls were performed by the chi-square test. A significant difference was found between ACL rupture subgroups in terms of genotype association (5A+ (5A/5A, 5A/6A): 37.5% in contact sports vs 20% in non-contact sports; P = 0.02). In allelic association, there were significant differences (6A: 81.2% in contact sports vs 89.1% in non-contact sports, 5A: 18.8% in contact sports vs 10.9% in non-contact sports, P = 0.01). The 5A+ genotype of MMP-3 was represented in ACL ruptures in contact sport participants. We propose that this sequence variant is a specific genetic element that should be included in a multifactorial model to understand the etiologies and risk factors for ACL rupture. PMID- 22057990 TI - Coagulation factor III (tissue factor) is required for vascularization in zebrafish embryos. AB - Tissue factor (coagulation factor III) is a cell surface receptor for coagulation factor VII/VIIa; it was initially recognized as an initiator of the extrinsic coagulation pathway. Recently, the zebrafish tissue factor gene (TF) has been cloned. Paralogs encode coagulation factors IIIa and IIIb; both show remarkable sequence identity to the human and mouse coagulation factor III gene. It has been reported that TF could have additional properties that are essential for normal embryonic development, since knockout of the murine coagulation factor III gene resulted in 90% embryonic lethality. We examined the role of coagulation factor IIIb (f3b) during zebrafish embryonic development. Expression analysis revealed that endogenous f3b was chronologically expressed in the pectoral fins and in the vicinity of the pharynx. Knockout of f3b by injection of an f3b morpholino at the one-to-two cell stage caused distinctive morphological defects in embryos, including edema in the fourth brain ventricle at early embryonic stages and occasional bleeding at later stages. Furthermore, f3b morphants displayed abnormal vascular patterning. We conclude that f3b is required for brain vascular development and for development of part of the somatic vasculature during embryogenesis in the zebrafish. PMID- 22057991 TI - Limited efficiency of universal mini-barcode primers for DNA amplification from desert reptiles, birds and mammals. AB - In recent years, DNA barcoding has emerged as a powerful tool for species identification. We report an extended validation of a universal DNA mini-barcode for amplification of 130-bp COI segments from 23 specimens collected from a desert environment, including 11 reptiles, five mammals and seven birds. Besides the standard double-annealing protocol, we also tested a more stringent single annealing protocol. The PCR success rate for the amplification of the mini barcode region was: mammals (4/5), reptiles (5/11) and birds (4/7). These findings demonstrate the limited utility of universal primers for mini barcoding, at least for these vertebrate taxa that we collected from the Saudi Arabian desert. PMID- 22057992 TI - Random regression models using different functions to model test-day milk yield of Brazilian Holstein cows. AB - We analyzed 152,145 test-day records from 7317 first lactations of Holstein cows recorded from 1995 to 2003. Our objective was to model variations in test-day milk yield during the first lactation of Holstein cows by random regression model (RRM), using various functions in order to obtain adequate and parsimonious models for the estimation of genetic parameters. Test-day milk yields were grouped into weekly classes of days in milk, ranging from 1 to 44 weeks. The contemporary groups were defined as herd-test-day. The analyses were performed using a single-trait RRM, including the direct additive, permanent environmental and residual random effects. In addition, contemporary group and linear and quadratic effects of the age of cow at calving were included as fixed effects. The mean trend of milk yield was modeled with a fourth-order orthogonal Legendre polynomial. The additive genetic and permanent environmental covariance functions were estimated by random regression on two parametric functions, Ali and Schaeffer and Wilmink, and on B-spline functions of days in milk. The covariance components and the genetic parameters were estimated by the restricted maximum likelihood method. Results from RRM parametric and B-spline functions were compared to RRM on Legendre polynomials and with a multi-trait analysis, using the same data set. Heritability estimates presented similar trends during mid-lactation (13 to 31 weeks) and between week 37 and the end of lactation, for all RRM. Heritabilities obtained by multi-trait analysis were of a lower magnitude than those estimated by RRM. The RRMs with a higher number of parameters were more useful to describe the genetic variation of test-day milk yield throughout the lactation. RRM using B-spline and Legendre polynomials as base functions appears to be the most adequate to describe the covariance structure of the data. PMID- 22057993 TI - Virulence characteristics and antimicrobial susceptibility of uropathogenic Escherichia coli strains. AB - Eight virulence factors associated with uropathogenic Escherichia coli (UPEC) were investigated in 204 clinical isolates of E. coli recovered from urine cultures at counts >=10(5). The bacteria were classified into two groups according to the number of leukocytes in urine samples from which they were isolated: group I <=8 leukocytes/hpf, 104 strains; group II >8 leukocytes/hpf, 100 strains. Two multiplex PCR systems were used to detect genes encoding adhesin P (pap), adhesin S (sfa), afimbrial adhesin I (afa), siderophore aerobactin (aer), alpha-hemolysin (hly), cytotoxic necrotizing factor type 1 (cnf1), and traT associated with serum resistance. The PAI marker for the virulence island identified in strains CFT072 and CVD432, a marker of enteroaggregative E. coli, was also investigated using PCR. The susceptibility profile of E. coli strains was determined by disk diffusion method. Ninety percent UPEC showed at least one of the virulence genes, the prevalence being traT (76%), aer (41%), PAI (32%), sfa (26%), pap (25%), cnf1 (18%), afa (6%), and hly (5%). There was no significant difference in the distribution of virulence genes between groups I and II. A significantly higher degree of virulence was detected in UPEC group II. The CVD432 gene was not detected in any of the UPECs. Fifty-nine percent of the strains were resistant to at least one of the antimicrobials that we tested; the most common being resistance to ampicillin (51%) and trimethoprim-sulfamethoxazole (44%). PMID- 22057994 TI - Association between interleukin 21 and Graves' disease. AB - Graves' disease (GD) is an organ-specific autoimmune thyroid disease; 25-50% of GD patients will develop Graves' ophthalmopathy (GO). The etiology of GD and GO may be multifactorial, but the immune response plays a central role. Many studies have reported that IL-21 has crucial roles in autoimmune diseases. We examined whether IL-21 is associated with the development of GD and GO. The serum concentration of IL-21 was tested in 40 primary GD patients, 42 treated GO patients and 24 healthy controls. Our data show that the serum level of IL-21 is associated with the development of GD. We also made an association study with the IL-21 gene polymorphisms rs4833837, rs907715 and rs13143866 in a comparison of 633 patients and 612 healthy controls from the Chinese population. This case control association study demonstrated that rs907715 SNP is significantly associated with GD, while the rs13143866 A allele is significantly associated with GO. The haplotypes A-G-G and A-A-A were found at higher and lower frequencies, respectively, in GD patients, suggesting a protective role for A-A A. However, there were no significant differences in the frequencies of these haplotypes between the GO patients and the control group. We found no association between IL-21 gene polymorphisms and the age of GD onset. We conclude that IL-21 is associated with GD and GO. PMID- 22057995 TI - Phylogenetic relationships of the Hucul horse from Romania inferred from mitochondrial D-loop variation. AB - The existence of the Hucul horse on Romanian territory has been documented from the very distant past; today Hucul is a unique breed that is part of the FAO Program for the Preservation of Animal Genetic Resources. We compared Hucul with several primitive European and Asiatic breeds in order to elucidate the origin of these horses. We analyzed a 683-bp mitochondrial DNA (mtDNA) D-loop fragment in a population of Hucul horses and compared the polymorphic sites with sequences from other primitive breeds, including Exmoor, Icelandic Pony, Sorraia, Przewalski Horse, Mongolian Wild Horse, Konik, and Shetland Pony, as well as with Arabian, Akhal Teke and Caspian Pony. The sequences were truncated to 247 bp to accommodate short sequence data for the other species. Eighty horses were analyzed; 35 polymorphic sites representing 33 haplotypes were observed. The mean percentage of polymorphic sites was 14.2% for this mtDNA fragment. A neighbor-joining phylogenetic tree was constructed based on Kimura two-parameter distances and the Network 3.111 software was used for phylogenetic analysis. The Hucul horse was classified separately from all other primitive breeds. It is possible that the Hucul horse is not part of the pony class, as it segregated apart from all primitive pony breeds. We found multiple origins in the maternal lineage of domestic horse breeds and demonstrated the uniqueness of the Hucul breed; its origins remain unclear. PMID- 22057996 TI - Diversity of pea (Pisum sativum) accessions based on morphological data for sustainable field pea breeding in Argentina. AB - We characterized 13 accessions of dry peas of different origins from various growing regions in Argentina, based on three replications of 20 plants cultivated in 2009 and 2010 in a greenhouse, with the objective of selecting those with favorable characteristics for use in breeding programs. Significant differences were found for length and width of stipule and pod, length of the internodes and leaflets, plant height, total number of nodes, number of nodes at the first pod, number of days to flowering and to harvest, number of pods and seeds per pod, 100-seed weight and grain diameter, demonstrating a high degree of genetic variability. Phenotypic correlation analysis demonstrated that large pods produced more seeds per pod, but the seed weight decreased. Plants with smaller number of nodes in the first pod were more productive. Estimates of genotypic correlation coefficients indicated a strong inherent association among the different traits. Clustering methods grouped the accessions into five clusters. Cluster 5 included two accessions and showed the highest values for length and width of stipules (4.9 and 4.5 cm, respectively), length of leaflets (7.43 cm) and days to flowering (122.6), while cluster 3, with one accession, and cluster 4, with two accessions, showed the highest values for number of seeds per pod (3.78 and 4.39), number of pods per plant (5.33 and 5.70), length of pods (5.54 and 5.72 cm), and width of pods (1.21 and 1.20 cm, respectively). We conclude that accessions in clusters 3 and 4 would be useful for crosses with other cultivars in pea breeding programs. PMID- 22057997 TI - Genetic and environmental effects on age at first farrowing in sows in southeastern Brazil. AB - We evaluated genetic and environmental factors affecting age at first farrowing of sows in the Brazilian southeast. For this purpose, 466 observations regarding the age at first farrowing were made for Dalland-C40(c) animals belonging to two herds. The effects of the environmental factors on this trait were assessed by means of a model that included, as random effects, the influence of the sow's father and mother and, as fixed effects, the influence the year of birth, the herd and the birth season, along with the covariable litter size at birth. The variance components were estimated using the derivative-free restricted maximum likelihood method. The estimated mean was 354.8 +/- 25.87 days, with a coefficient of variation of 7.29%. Significant effects on the trait were observed for the herd, the year and the season of birth; but a linear effect of litter size at birth on the age at first farrowing was not observed. The boar did not significantly contribute to the variation occurring among the sows, whereas the sow's mother caused significant variation. The heritability estimate for the age at first farrowing was 0.44 +/- 0.15, which is considered high. We concluded that herd effect and year and season of birth should be taken into consideration for an accurate genetic comparison; consequently, the animals should be joined into contemporary groups. PMID- 22057998 TI - Identification of neutral genes at pollen sterility loci Sd and Se of cultivated rice (Oryza sativa) with wild rice (O. rufipogon) origin. AB - Pollen sterility is one of the main hindrances against the utilization of strong intersubspecific (indica-japonica) heterosis in rice. We looked for neutral alleles at known pollen sterility loci Sd and Se that could overcome this pollen sterility characteristic. Taichung 65, a typical japonica cultivar, and its near isogenic lines E7 and E8 for pollen sterility loci Sd and Se were employed as tester lines for crossing with 13 accessions of wild rice (O. rufipogon). Pollen fertility and genotypic segregations of the molecular markers tightly linked with Sd and Se loci were analyzed in the paired F(1)s and F(2) populations. One accession of wild rice (GZW054) had high pollen fertility in the paired F(1)s between Taichung 65 and E7 or E8. Genotypic segregations of the molecular markers tightly linked with Sd and Se loci fit the expected Mendelian ratio (1:2:1), and non-significances were shown among the mean pollen fertilities with the maternal, parental, and heterozygous genotypes of each molecular markers tightly linked with Sd and Se loci. Evidentially, it indicated that the alleles of Sd and Se loci for GZW054 did not interact with those of Taichung 65 and its near isogenic lines, and, thus were identified as neutral alleles Sd(n) and Se(n). These neutral genes could become important germplasm resources for overcoming pollen sterility in indica-japonica hybrids, making utilization of strong heterosis in such hybrids viable. PMID- 22057999 TI - Meta-analysis of an association of codon 72 polymorphisms of the p53 gene with increased endometrial cancer risk. AB - Polymorphisms of the p53 gene have been associated with susceptibility to endometrial cancer. However, whether there is a specific association is still controversial. We investigated a possible association between p53 codon 72 polymorphism and endometrial cancer risk by conducting a meta-analysis. Publications addressing this association were selected from the Pubmed, Embase and CBM databases (up to January 2011). Data were extracted from the studies by two independent reviewers. The meta-analysis was performed using RevMan 5.0.25 and STATA 9.2 softwares. The odds ratio (OR) with 95% confidence intervals (CI) was calculated. Then, 10 case-control studies were retrieved, with a total of 917 endometrial cancer patients and 1680 healthy controls. Meta-analysis results showed that the Pro allele and Pro carrier (Arg/Pro + Pro/Pro) of p53 codon 72 polymorphism were significantly related with endometrial cancer risk (OR = 1.25, 95%CI = 1.10-1.41, P = 0.0005; OR = 1.34, 95%CI = 1.12-1.59, P = 0.001, respectively). In the subgroup analysis, based on ethnicity, studies were divided into Asian and Caucasian populations; the Pro allele and Pro carrier (Arg/Pro + Pro/Pro) of p53 codon 72 polymorphism were significantly related with endometrial cancer risk in Asian populations (OR = 1.41, 95%CI = 1.19-1.66, P < 0.0001; OR = 1.66, 95%CI = 1.30-2.13, P < 0.0001, respectively), but not in Caucasian populations (both P > 0.05). We concluded that the Pro allele (Arg/Pro + Pro/Pro) of p53 codon 72 polymorphism is a potential risk factor for endometrial cancer. PMID- 22058000 TI - Lack of association between catalase gene polymorphism (T/C exon 9) and susceptibility to vitiligo in a Turkish population. AB - Accumulation of hydrogen peroxide (H(2)O(2)) and low catalase (CAT) activity have been demonstrated in the epidermis of vitiligo patients. We investigated a possible association between the CAT exon 9 (Asp-389) gene and vitiligo susceptibility in the Turkish population. Thirty-four patients with vitiligo and 49 gender, age and ethnic matched controls were enrolled in the study. Genotyping was done by PCR-RFLP. The CAT exon 9 (Asp-389) genotype and allele frequencies of vitiligo patients did not differ significantly from those of healthy controls. We found no association between CAT (Asp-389) gene polymorphism and vitiligo susceptibility in Turkish vitiligo patients. PMID- 22058001 TI - Vascular endothelial growth factor gene polymorphisms and colorectal cancer risk: a meta-analysis. AB - Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in a number of pathologic processes, including angiogenesis, tumor growth and metastasis. Polymorphisms of the VEGF gene have been associated with susceptibility to colorectal cancer (CRC). However, the specific association still remains controversial. We made a meta-analysis of the association between VEGF gene polymorphisms and CRC risk. Only eight case control studies were retrieved, with a total of 2337 CRC patients and 2032 healthy controls. Six VEGF gene polymorphisms were addressed in all studies included, +936C>T (rs3025039), -2578C>A (rs699947), -1154G>A (rs1570360), 634G>C (rs2010963), -460C>T (rs833061), and +405C>G (rs2010963). There was a significant association between -2578C>A polymorphism and susceptibility to CRC in the comparison of C allele carriers (CC + CA) versus AA (odds ratio = 0.77, 95% confidence interval = 0.62-0.96, P = 0.02). No association was found between +936C>T, -1154G>A, -634G>C, -460C>T, and +405C>G with susceptibility to CRC. We conclude that the C allele carrier (CC + CA) of VEGF -2578C>A polymorphism appears to be a protective factor for CRC. PMID- 22058002 TI - Influence of glutathione S-transferase polymorphisms on type-2 diabetes mellitus risk. AB - Glutathione S-transferase (GST) protects cells against oxidative stress. We evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing type-2 diabetes mellitus and on glycemic control. We also investigated the effects of smoking combined with these polymorphisms on type-2 diabetes mellitus risk. We enrolled 100 type-2 diabetes mellitus patients and 100 healthy controls matched for age, gender and origin, from the Sinai area of Egypt. Fasting serum glucose, HbA(1c) and lipid profiles were determined. Two polymorphisms were identified by multiplex PCR within the GST genes: GSTM1 and GSTT1. The proportion of the GSTT1- and GSTM1-null genotypes was significantly greater in diabetic patients when compared to controls. Patients carrying both null polymorphisms had a 3.17-fold increased risk of having type-2 diabetes mellitus compared to those with normal genotypes of these two genes (P = 0.009). Additionally, patients with the GSTT1-null genotype had higher levels of triglycerides and very low-density lipoprotein cholesterol compared to those with the GSTT1-present genotype. On the other hand, patients with the GSTM1- null genotype had significantly higher levels of HbA(1c) and significantly higher diastolic blood pressure compared to those with the GSTM1- present genotype. The interaction between these genotypes and smoking status was not significant. These results give evidence that the GSTT1- and GSTM1-null genotypes, alone or combined, are associated with increased risk of type-2 diabetes mellitus, regardless of smoking status. Only the GSTM1-null genotype had an effect on glycemic control. PMID- 22058003 TI - Quantitative trait loci affecting lactose and total solids on chromosome 6 in Brazilian Gir dairy cattle. AB - Fourteen Brazilian Gir sire families with 657 daughters were analyzed for quantitative trait loci (QTL) on chromosome 6 affecting lactose and total solids. Cows and sires were genotyped with 27 microsatellites with a mean spacing between markers of 4.9 cM. We used a 1% chromosome-wide threshold for QTL qualification. A QTL for lactose yield was found close to marker MNB66 in three families. A QTL for total solid yield was identified close to marker BMS2508 in three families. A QTL for lactose percentage, close to marker DIK1182, was identified in two families. A QTL for total solid percentage, close to marker MNB208, was identified in four families. These QTLs could be used for selection of animals in dairy production systems. PMID- 22058004 TI - Microsatellite analysis as a tool for discriminating an interfamily hybrid between olive flounder and starry flounder. AB - An interspecific artificial hybrid was produced between two economically important aquaculture flatfish: olive flounder (Paralichthys olivaceus) and starry flounder (P. stellatus). This hybrid displays the rapid growth characteristic of the former and tolerance to low temperatures and low salinity of the latter, but the genetics of inheritance in this hybrid have not been elucidated. Polymorphic microsatellite markers developed for P. olivaceus and P. stellatus were tested to determine if these markers can be used for analysis of parentage and genetic inheritance. Multiplex PCR using two primer sets that were specific to each species produced PCR products of different sizes; these could be used for the identification of interspecific hybrids. Among the 192 primers derived from olive flounder, 25.5% of the primer sets successfully amplified genomic DNA from starry flounder, and 23% of the 56 primer sets originating from starry flounder amplified DNA from olive flounder. Analysis of genetic inheritance in the hybrid using seven of the 62 microsatellite markers common to both species demonstrated classic Mendelian inheritance of these markers in the hybrid progeny, with the exception of one locus identified as a null allele in the hybrid. These results demonstrate that cross-specific microsatellite markers can be used tools for parentage analysis of hybrid flatfish, for mapping quantitative trait loci, for marker-assisted selective breeding, and for studies of the evolution of fish. PMID- 22058005 TI - Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective? AB - The widespread use of systemic and local therapies aimed at spinal metastatic lesions secondary to breast cancer has increased the incidence of mixed osteolytic/osteoblastic patterns of bony disease. The complex structure of these lesions requires novel therapeutic approaches to both reduce tumor burden and restore structural stability. In photodynamic therapy (PDT), a minimally invasive approach can be used to employ light to activate a photosensitizing agent that preferentially accumulates in tumor tissue, leading to cell toxicity and death. Previous work in an osteolytic rat model (MT-1) demonstrated that PDT effectively ablates tumor and improves vertebral structural properties. The aim of this study was to assess the efficacy of PDT in a rat model of mixed osteolytic/osteoblastic spinal metastases. Mixed spinal metastases were generated through intracardiac injection of Ace-1 canine prostate cancer cells into female athymic rats (day 0). A single PDT treatment was applied to lumbar vertebra L2 of tumor-bearing and healthy control rats (day 14). PDT-treated and untreated control rats were euthanized and excised spines imaged with MUCT to assess bone quality (day 21). Spines were mechanically tested or histologically processed to assess mechanical integrity, tumor burden, and remodelling properties. Untreated tumor-bearing vertebrae showed large areas of osteolysis and areas of immature, new bone formation. The overall bone quality resulting from these lesions consisted of decreased structural properties but without a significant reduction in mechanical integrity. PDT was shown to significantly decrease tumor burden and osteoclastic activity, thereby improving vertebral bone structural properties. While non-tumor bearing vertebrae exhibited significantly more new bone formation following PDT, the already heightened level of new bone formation in the mixed tumor-bearing vertebrae was not further increased. As such, the effect of PDT on mixed metastases may be more influenced by suppression of osteoclastic resorption as opposed to the triggering of new bone formation. PMID- 22058006 TI - Designing N-heterocyclic carbenes: simultaneous enhancement of reactivity and enantioselectivity in the asymmetric hydroacylation of cyclopropenes. AB - Faster, higher, stronger! The N-heterocyclic carbene (NHC) catalyzed diastereo- and enantioselective hydroacylation of cyclopropenes affords structurally valuable acylcyclopropanes. A new family of electron-rich, 2,6-dimethoxyphenyl substituted NHCs induces excellent reactivity and enantioselectivity. Preliminary kinetic studies unambiguously demonstrated the superiority of this family of catalysts over known NHCs in this challenging transformation. PMID- 22058007 TI - Psychological distress in cancer survivors: the further development of an item bank. AB - OBJECTIVE: Assessment of psychological distress by patient report is necessary to meet patients' needs throughout the cancer journey. We have previously developed an item bank to assess psychological distress but not evaluated it for cancer survivors. Our first aim in this study was to test whether we could extend our item bank to include cancer survivors. The second aim was to examine whether the item bank could assess positive affect as a single construct alongside negative psychological symptoms. METHODS: Responses from 1315 cancer survivors to the Hospital Anxiety and Depression Scale (HADS) and the Positive and Negative Affect Scale (PANAS) were considered for inclusion in a pre-existing item bank created from a heterogeneous sample of 4914 cancer patients. Differential item functioning (DIF) was used to assess whether HADS responses drawn from the two samples were equivalent. Common-item equating was used to anchor the shared (HADS) items, whilst the PANAS items were added. Item fit was evaluated at each stage, and misfitting items were removed. Unidimensionality was assessed with a principal components factor analysis. RESULTS: The DIF analysis did not reveal any differences between the HADS item locations from the two samples. Three misfitting PANAS items were removed, resulting in a final unidimensional bank of 80 items with good internal reliability (alpha = 0.85). CONCLUSION: The new item bank is valid for use across the cancer journey, including cancer survivors, and modestly improves the assessment of all levels of psychological distress and positive psychological function. PMID- 22058008 TI - Glucose status in patients with acromegaly receiving primary treatment with the somatostatin analog lanreotide. AB - To describe glucose status changes in patients with acromegaly receiving somatostatin analog lanreotide as primary treatment. This retrospective, single center study conducted during 1996-2008, included acromegalic patients receiving primary lanreotide treatment. Baseline and last follow-up visit assessments included glucose status (according to American Diabetes Association criteria), growth hormone (GH), and insulin-like growth factor-1 (IGF-1) levels. Glucose control was considered improved when fasting plasma glucose or antidiabetic treatments were reduced, and deteriorated if fasting glucose was the same/higher but with increased antidiabetic treatments. 42 patients (median age 50 years; range 29-75 years) were included. At baseline, 26 (62%) were normoglycemic, eight (19%) had impaired glucose tolerance/fasting glycemia, and eight (19%) had diabetes mellitus; family history of diabetes mellitus was significantly associated with abnormal glucose status. At final visit, the mean (SE) lanreotide dose was 108 (21) mg/month. Median treatment duration was 23 months, range 3-138 months, and 74% of patients received the 120-mg dose. Median GH levels decreased significantly (baseline, 12 [5-20] MUg/l; final visit, 2.1 [1.0-4.7] MUg/l; P < 0.0001); IGF-1 levels were age- and sex-normalized in 33% of patients. Glucose control deteriorated in seven patients (17%) and improved from abnormal levels in 10 (24%). Deterioration was associated with smaller GH decreases (median change, 3.4 MUg/l vs. -10.7 MUg/l, P = 0.014) and improvement with trend to lower BMI and younger age. During primary lanreotide treated acromegalic patients 60% had no change, 24% had an improvement and 17% had a worsening of glucose status. Deterioration was significantly associated with smaller GH decreases during primary lanreotide treatment. PMID- 22058009 TI - Effect of retreatment on the end-stage sudden deafness. AB - Microcirculatory disturbance of inner ear is probably one of the important etiological factors of sudden deafness. The purpose of this study was to evaluate the effect of retreatment on the end-stage sudden deafness. For this purpose, the patients who met with the criteria for sudden deafness and showed poor response to conventional therapy over 2 months were assigned randomly to the retreatment group. Pure tone audiometry was conducted before and after retreatment among the 103 patients (112 ears). Sodium bicarbonate and dexamethasone were injected by intravenous drip for 2 days and batroxobin 5BU for 6 days. Data were analyzed using analysis of variance and t test to determine the efficacy of retreatment. These data show that the efficacy rate in retreatment group was 46.43% and the difference between before and after retreatment was significant (P < 0.01). It was, therefore, concluded that retreatment of the end-stage sudden deafness could improve the audition of the patients and should be valuable in clinics. In this regard, the combination of sodium bicarbonate and dexamethasone proved a rational therapeutic regimen for the end-stage sudden deafness. However, further large size multicenter studies will be required for independent validation of these findings. PMID- 22058011 TI - Economic impact of enoxaparin versus unfractionated heparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke: a hospital perspective of the PREVAIL trial. AB - BACKGROUND: The PREVAIL (Prevention of VTE [venous thromboembolism] after acute ischemic stroke with LMWH [low-molecular-weight heparin] and UFH [unfractionated heparin]) study demonstrated a 43% VTE risk reduction with enoxaparin versus UFH in patients with acute ischemic stroke (AIS). A 1% rate of symptomatic intracranial and major extracranial hemorrhage was observed in both groups. OBJECTIVE: To determine the economic impact, from a hospital perspective, of enoxaparin versus UFH for VTE prophylaxis after AIS. DESIGN: A decision-analytic model was constructed and hospital-based costs analyzed using clinical information from PREVAIL. Total hospital costs were calculated based on mean costs in the PremierTM database and from wholesalers acquisition data. Costs were also compared in patients with severe stroke (National Institutes of Health Stroke Scale [NIHSS] score >=14) and less severe stroke (NIHSS score <14). RESULTS: The average cost per patient due to VTE or bleeding events was lower with enoxaparin versus UFH ($422 vs $662, respectively; net savings $240). The average anticoagulant cost, including drug-administration cost per patient, was lower with UFH versus enoxaparin ($259 vs $360, respectively; net savings $101). However, when both clinical events and drug-acquisition costs were considered, the total hospital cost was lower with enoxaparin versus UFH ($782 vs $922, respectively; savings $140). Hospital cost-savings were greatest ($287) in patients with NIHSS scores >=14. CONCLUSIONS: The higher drug cost of enoxaparin was offset by the reduction in clinical events as compared to the use of UFH for VTE prophylaxis after an AIS, particularly in patients with severe stroke. PMID- 22058013 TI - Long-term oral administration of glucosamine or chondroitin sulfate reduces destruction of cartilage and up-regulation of MMP-3 mRNA in a model of spontaneous osteoarthritis in Hartley guinea pigs. AB - Histological and molecular changes were examined to investigate the effects of long-term administration of glucosamine (GlcN) and chondroitin sulfate (CS) in a model of spontaneous osteoarthritis (OA) in Hartley guinea pigs. Three groups of female 3-week-old Hartley guinea pigs received GlcN, CS, and neither agent, respectively. Five animals in each group were sacrificed at 8, 12, and 18 months of age. At 8 months of age, Hartley guinea pigs had severe degeneration of knee joint cartilage, chondrocyte apoptosis, marked reduction of tissue total RNA, decreases of aggrecan and collagen type 2 mRNAs, and increases in MMP-3 and MMP-8 mRNAs. Long-term administration of GlcN and CS reduced cartilage degeneration at 8 months of age. The marked loss of total RNA and the increase in MMP-3 mRNA were also inhibited by GlcN and CS. Thus, long-term oral administration of GlcN or CS inhibits OA progression, maintains total RNA and down-regulates MMP-3 mRNA in a spontaneous OA model in Hartley guinea pigs. PMID- 22058014 TI - A novel nonsense mutation in PAX9 is associated with sporadic hypodontia. AB - The most important events during the regulation of tooth development were inductive interactions between the epithelial and mesenchymal tissues. The expression of Pax9 had been shown to specifically mark the mesenchymal regions at the prospective sites of all teeth prior to any morphological manifestations. Here, we investigated the PAX9 gene as a candidate gene for hypodontia in five unrelated Chinese patients with tooth agenesis. Direct sequencing and restriction enzyme analysis revealed a novel heterozygous mutation c.480C>G (p.160Tyr>X, Y160X) in a patient who was missing 20 permanent teeth (the third molars excluded) and 6 primary teeth. The mutation was a nonsense mutation, leading to a premature stop codon in exon 2 of PAX9 gene. PCR analysis of complementary DNA from cultured lymphocytes of the affected individual could not indicate the complete degradation of the mutated transcript. Promoter reporter assays revealed reduced transcriptional activity of the mutated PAX9 protein suggesting that the severe phenotype may result from haploinsufficiency of PAX9. In another patient with 15 missing permanent teeth (the third molars excluded), we found the c.219insG mutation previously reported by Stockton. PMID- 22058015 TI - An adaptation of the human HepaRG cells to the in vitro micronucleus assay. AB - The in vitro micronucleus test is considered as an attractive tool for genotoxicity testing of chemicals because of its simplicity of scoring and wide applicability in different cell types. However, most of the cells currently in use are devoid of the enzyme equipment required for activation of promutagens in the genotoxic metabolites. We postulated that the human HepaRG cell line, which can express xenobiotic metabolising enzymes at levels close to those found in primary human hepatocytes and has retained the indefinite growth capacity of transformed cells, could represent a more suitable model for genotoxicity testing of chemicals requiring metabolic activation. Based on the recommendations of the Organisation for Economic Co-operation and Development test guideline TG 487 for testing of chemicals, HepaRG cell cultures containing >80% mature hepatocytes were treated in situ with various chemicals for 24 h followed by a 3-day mitogenic stimulation with epidermal growth factor without cytokinesis block. In such culture conditions, HepaRG cells underwent >1.5 cell cycle per cell during the mitogenic stimulation. While non-genotoxic compounds (mannitol and staurosporine) did not increase the rate of micronucleated mononucleated cells, all aneugens (colchicine, nocodazole and dichlorodiphenyldichloroethylene) as well as the direct acting clastogen methyl methanesulfonate and clastogens requiring metabolic activation (aflatoxin B1, benzo(a)pyrene and 2-nitrofluorene) induced a statistically significant concentration-related increase in the number of mono-micronucleated cells. The micronucleus test was also performed after 7 day repeat exposure of HepaRG cells to the chemicals. Noticeably, a time dependent effect was obtained with the three clastogens requiring metabolic activation. In conclusion, our results obtained with HepaRG hepatocytes exposed to various genotoxic compounds requiring or not bioactivation, compared favorably with those reported in various other cell types. They support the view that metabolically competent HepaRG cells have unique potential benefits for testing genotoxic compounds using the in vitro micronucleus assay. PMID- 22058016 TI - Simvastatin promotes osteogenic differentiation of mouse embryonic stem cells via canonical Wnt/beta-catenin signaling. AB - Simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, has been known to reduce cholesterol biosynthesis. However, recent studies demonstrate that simvastatin shows diverse cholesterol-independent functions including cellular differentiation. In this study, we investigated the stimulatory effect of simvastatin on the osteogenic differentiation of mouse embryonic stem cells (ESCs). The osteogenic effect of simvastatin was observed at relatively low doses (ranging from 1 nM to 200 nM). Incubation of ESCs in simvastatin-supplemented osteogenic medium significantly increased alkaline phosphatase (ALP) activity at day 7. The matrix mineralization was also augmented and demonstrated pivotal levels after 14 days incubation of simvastatin. Osteogenic differentiation of ESCs by simvastatin was determined by upregulation of the mRNA expression of runtrelated gene 2 (Runx2), osterix (OSX), and osteocalcin (OCN) as osteogenic transcription factors. Moreover, the increased protein expression of OCN, osteopontin (OPN), and collagen type I (Coll I) was assessed using Western blot analysis and immunocytochemistry. However, the blockage of canonical Wnt signaling by DKK-1 downregulated simvastatin-induced ALP activity and the mRNA expression of each osteogenic transcription factor. Furthermore, the beta-catenin specific siRNA transfection decreased the protein levels of OCN, OPN, and Coll I. Collectively, these findings suggest that simvastatin enhances the differentiation of ESCs toward osteogenic lineage through activation of canonical Wnt/beta-catenin signaling. PMID- 22058017 TI - DNA aptamers against the receptor binding region of hemagglutinin prevent avian influenza viral infection. AB - The entrance of influenza virus into host cells is facilitated by the attachment of the globular region of viral hemagglutinin to the sialic acid receptors on host cell surfaces. In this study, we have cloned the cDNA fragment encoding the entire globular region (residues 101-257) of hemagglutinin of the H9N2 type avian influenza virus (A/ck/Korea/ms96/96). The protein segment (denoted as the H9 peptide), which was expressed and purified in E. coli, was used for the immunization of BALB/c mice to obtain the anti-H9 antiserum. To identify specific DNA aptamers with high affinity to H9 peptide, we conducted the SELEX method; 19 aptamers were newly isolated. A random mixture of these aptamers showed an increased level of binding affinity to the H9 peptide. The sequence alignment analysis of these aptamers revealed that 6 aptamers have highly conserved consensus sequences. Among these, aptamer C7 showed the highest similarity to the consensus sequences. Therefore, based on the C7 aptamer, we synthesized a new modified aptamer designated as C7-35M. This new aptamer showed strong binding capability to the viral particles. Furthermore, it could prevent MDCK cells from viral infection by strong binding to the viral particles. These results suggest that our aptamers can recognize the hemagglutinin protein of avian influenza virus and inhibit the binding of the virus to target receptors required for the penetration of host cells. PMID- 22058018 TI - Selection and optimization of asymmetric siRNA targeting the human c-MET gene. AB - The silencing of specific oncogenes via RNA interference (RNAi) holds great promise for the future of cancer therapy. RNAi is commonly carried out using small interfering RNA (siRNA) composed of a 19 bp duplex region with a 2 nucleotide overhang at each 3' end. This classical siRNA structure, however, can trigger non-specific effects, which has hampered the development of specific and safe RNAi therapeutics. Previously, we developed a novel siRNA structure, called asymmetric shorter-duplex siRNA (asiRNA), which did not cause the non-specific effects triggered by conventional siRNA, such as off-target gene silencing mediated by the sense strand. In this study, we first screened potent asiRNA molecules targeting the human c-MET gene, a promising anticancer target. Next, the activity of a selected asiRNA was further optimized by introducing a locked nucleic acid (LNA) to maximize the gene silencing potency. The optimized asiRNA targeted to c-MET may have potential as a specific and safe anticancer RNAi therapeutic. PMID- 22058019 TI - A subset of OsSERK genes, including OsBAK1, affects normal growth and leaf development of rice. AB - Since the identification of BRI1-Associated receptor Kinase 1 (BAK1), a member of the Somatic Embryogenesis Receptor Kinase (SERK) family, the dual functions of BAK1 in BR signaling and innate immunity in Arabidopsis have attracted considerable attention as clues for understanding developmental processes that must be balanced between growth and defense over the life of plants. Here, we extended our research to study cellular functions of OsSERKs in rice. As it was difficult to identify an authentic ortholog of AtBAK1 in rice, we generated transgenic rice in which the expression of multiple OsSERK genes, including OsBAK1, was reduced by OsBAK1 RNA interference. Resulting transgenic rice showed reduced levels of Os-BAK1 and decreased sensitivity to BL, leading to semidwarfism in overall growth. Moreover, they resulted in abnormal growth patterns, especially in leaf development. Most of the OsBAK1RNAi transgenic rice plants were defective in the development of bulliform cells in the leaf epidermal layer. They also showed increased expression level of pathogenesis-related gene and enhanced susceptibility to a rice blast-causing fungal pathogen, Magnaporthe oryzae. These results indicate that OsSERK genes, such as OsBAK1, play versatile roles in rice growth and development. PMID- 22058020 TI - Buffered memory: a hypothesis for the maintenance of functional, virus-specific CD8(+) T cells during cytomegalovirus infection. AB - Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and both CD4(+) and CD8(+) CMV-specific T cells are essential. These virus-specific T cells persist in exceptionally large numbers during the infection, traffic into peripheral tissues and remain functional, making CMV an attractive vaccine vector for driving "CMV-like" T cell responses against recombinant antigens of choice. However, the mechanisms by which these T cells persist and differentiate while remaining functional are still poorly understood, and we have no means to promote their development in immune-compromised patients at risk for CMV disease. In this review, I will briefly summarize our current knowledge of CMV-specific CD8(+) T cells and propose a mechanism that may explain their maintenance and preservation of function during chronic infection. PMID- 22058021 TI - Mechanisms controlling granule-mediated cytolytic activity of cytotoxic T lymphocytes. AB - Cytotoxic T lymphocytes (CTL) play a critical role in immunity against viruses and cancer. The antigen receptor or T-cell receptor (TCR) on CTL determines the specificity toward target cells. The CD8 co-receptor functions in concert with the TCR to enhance TCR-mediated signaling, accounting for the remarkable sensitivity and swift signaling kinetics of the CTL response. The latter ensures efficient delivery and release of lytic granules, resulting in sensitive and rapid destruction of target cells. PMID- 22058022 TI - Influence of body condition on reproductive output in the guinea pig. AB - Reproduction is expensive. Substantial body reserves (i.e. high body condition) are usually required for females to undertake offspring production. In many vertebrates, maternal body condition positively influences reproductive output, and emaciated individuals skip reproduction. However, the impact of extremely high body condition, more specifically obesity, on animal reproductive performance remains poorly understood and research has generated contradictory results. For instance, obesity negatively affects fertility in women, but does not influence reproductive capacity or reproductive output in laboratory rodents. We examined the influence of high body condition on reproductive status and reproductive output in the guinea pig. In captivity, when fed ad libitum, guinea pigs store large amounts of fat tissues and exhibit a tendency for obesity. Our results show that obesity negatively affected reproduction in this species: both the proportion of fertile females and litter size were lower in the fattest females. Therefore, guinea pigs may represent suitable organisms to better understand the negative effect of obesity on reproduction. PMID- 22058023 TI - Microporous aluminoborates with large channels: structural and catalytic properties. AB - Channel zapping: PKU-1 and newly synthesized PKU-2 (Al(2)B(5)O(9)(OH)(3)?n H(2)O; see picture) possess microporous structures with 18-ring and 24-ring channels, respectively. They show high reactivity and size selectivity in the cyanosilylation of aldehydes as heterogeneous Lewis acid catalysts. The different channel sizes determine the substrate selectivity. These examples demonstrate the potential of octahedron-based aluminoborate channels in catalysis. PMID- 22058024 TI - Nucleostemin-like 1 is required for embryogenesis and leaf development in Arabidopsis. AB - Arabidopsis NSN1 encodes a nucleolar GTP-binding protein and is required for flower development. Defective flowers were formed in heterozygous nsn1/+ plants. Homozygous nsn1 plants were dwarf and exhibited severe defects in reproduction. Arrests in embryo development in nsn1 could occur at any stage of embryogenesis. Cotyledon initiation and development during embryogenesis were distorted in nsn1 plants. At the seedling stage, cotyledons and leaves of nsn1 formed upward curls. The curled leaves developed meristem-like outgrowths or hyperplasia tissues in the adaxial epidermis. Long and enlarged pavement cells, characteristic of the abaxial epidermis of wild type plants, were found in the adaxial epidermis in nsn1 leaves, suggesting a disoriented leaf polarity in the mutant. The important role of NSN1 in embryo development and leaf differentiation was consistent with the high level expression of the NSN1 gene in the developing embryos and the primordia of cotyledons and leaves. The CLAVATA 3 (CLV3) gene, a stem cell marker in the Arabidopsis shoot apical meristem (SAM), was expressed in expanded regions surrounding the SAM of nsn1 plants, and induced ectopically in the meristem-like outgrowths in cotyledons and leaves. The nsn1 mutation up-regulated the expression levels of several genes implicated in the meristem identity and the abaxial cell fate, and repressed the expression of other genes related to the specification of cotyledon boundary and abaxial identity. These results demonstrate that NSN1 represents a novel GTPase required for embryogenesis, leaf development and leaf polarity establishment in Arabidopsis. PMID- 22058025 TI - Karyotyping of barley chromosomes by a new fluorescence banding technique combined with scanning probe microscopy. AB - Fluorescence banding has been used to classify chromosomes, except those of barley. Four of the seven barley chromosomes are indistinguishable by length or arm ratio. C-banding has been used for classification; however, it requires a long aging period. Here, we describe a new fluorescence banding method for barley. The chromosomes are treated with warm acetate followed by staining with a fluorescent dye, YOYO-1. Using this method, all seven barley chromosomes can be clearly distinguished. Atomic force microscopy and scanning near-field microscopy analyses revealed that the surfaces of the banded chromosomes were flat, indicating that the fluorescence intensity reflected the internal DNA density or condensation of chromatin. PMID- 22058026 TI - Should we shift toward higher blood pressure targets in patients with chronic kidney disease? AB - Hypertension is the leading cause of death worldwide and is responsible for a significantly increased burden of cardiovascular events and progression to end stage kidney disease in patients with chronic kidney disease (CKD). The fundamentals of therapeutics in patients with hypertension and CKD are both the use of specific renal protecting agents and the achievement of tight blood pressure control - i.e., blood pressure values below 130/80 mm Hg. When the evidence underpinning a "tight blood pressure target control" recommendation is analyzed, hypertension guidelines appear to be largely extrapolating to people with CKD the key findings of large trials conducted in the general population and other high cardiovascular risk populations, while renal societies guidelines are primarily influenced by observational data reporting renal outcomes and small scale randomized studies, and have not always incorporated recent evidence from systematic reviews. In this narrative review, we present existing guidelines and evidence for 2 crucial clinical questions in the management of hypertension of CKD: (i) should we, and by how much should we, lower blood pressure in people with CKD and (ii) are there agents which are specifically beneficial in the CKD population, independent of blood pressure control. PMID- 22058027 TI - Targeted therapies in diabetic nephropathy: an update. AB - Diabetic nephropathy is the most common cause of end-stage renal disease worldwide. Various pathways in addition to the renin-angiotensinogen system have been implicated in the pathogenesis of diabetic nephropathy. Strategies to interrupt these pathophysiological pathways are a key to the development of new targeted therapies to prevent progression of diabetic nephropathy and are on the horizon. The various pharmacological drugs tried include aliskiren, a direct renin inhibitor blocking the first step in the renin pathway, and pentoxifylline and mammalian target of rapamycin inhibitors, which have antiinflammatory properties and have shown some promising results in management of diabetic nephropathy. Others include endothelin antagonists and vitamin D analogs which have been shown to decrease urinary albumin excretion. Inhibitors of advanced glycation and oxidative stress and plasminogen activator inhibitor-1 have proved useful in animal models of diabetic nephropathy. Others include ruboxistaurin, which blocks protein kinase C overexpression. Such targeted therapies would halt and might even reverse progression of diabetic nephropathy. PMID- 22058028 TI - Simultaneous multicystic kidney and Anderson-Fabry disease: 2 separate entities or same side of the coin. AB - We present the case of a 54-year-old man with multicystic kidney and concomitant Anderson-Fabry disease. He was referred to our hospital with multiple renal and hepatic cysts, without apparent family history of autosomal dominant polycystic kidney disease. His clinical history suggested Anderson-Fabry disease, so an extensive work-up for Anderson-Fabry disease was subsequently undertaken. The alpha-galactosidase activity in his serum was low, and a final diagnosis of Anderson-Fabry disease with concomitant multicystic kidney was confirmed by genetic analysis. PMID- 22058029 TI - Youyou Tu honored by the Lasker award. PMID- 22058030 TI - Systematic temperature signaling regulates behavior plasticity. PMID- 22058031 TI - Genetic engineering and enzyme research in lignocellulosic ethanol production. PMID- 22058032 TI - Romance of the three kingdoms: RORgammat allies with HIF1alpha against FoxP3 in regulating T cell metabolism and differentiation. AB - Regulatory T (Treg) cells play an essential role in immune homeostasis by controlling the function of various immune effector cells, including RAR-related orphan receptor gammat(+) (RORgammat(+)) T helper 17 (Th17) cells. Foekhead box P(3) (FoxP(3)) is the master regulator of Treg cell function, while RORgammat is the key transcription factor for the induction of the interleukin (IL)-17 family of cytokines during Th17 cell differentiation. FoxP3 can directly interact with and negatively regulate the function of RORgammat, to determine the balance between induced Treg (iTreg) and Th17 cell polarization. Two recent independent studies from the Pan and Chi Labs have shown how hypoxia-inducible factor 1 alpha (HIF1alpha) is able to tip the balance of T cell differentiation toward the Th17 lineage by responding to the local changes in metabolic shift or an increase in proinflammatory mediators in the microenvironment. By allying with HIF1alpha, RORgammat wins the fight against FoxP3 and Treg cell commitment. PMID- 22058033 TI - Role of plant autophagy in stress response. AB - Autophagy is a conserved pathway for the bulk degradation of cytoplasmic components in all eukaryotes. This process plays a critical role in the adaptation of plants to drastic changing environmental stresses such as starvation, oxidative stress, drought, salt, and pathogen invasion. This paper summarizes the current knowledge about the mechanism and roles of plant autophagy in various plant stress responses. PMID- 22058034 TI - Mechanism and methods to induce pluripotency. AB - Pluripotent stem cells are able to self-renew indefinitely and differentiate into all types of cells in the body. They can thus be an inexhaustible source for future cell transplantation therapy to treat degenerative diseases which currently have no cure. However, non-autologous cells will cause immune rejection. Induced pluripotent stem cell (iPSC) technology can convert somatic cells to the pluripotent state, and therefore offers a solution to this problem. Since the first generation of iPSCs, there has been an explosion of relevant research, from which we have learned much about the genetic networks and epigenetic landscape of pluripotency, as well as how to manipulate genes, epigenetics, and microRNAs to obtain iPSCs. In this review, we focus on the mechanism of cellular reprogramming and current methods to induce pluripotency. We also highlight new problems emerging from iPSCs. Better understanding of the fundamental mechanisms underlying pluripotenty and refining the methodology of iPSC generation will have a significant impact on future development of regenerative medicine. PMID- 22058035 TI - Expanding neurotransmitters in the hypothalamic neurocircuitry for energy balance regulation. AB - The current epidemic of obesity and its associated metabolic syndromes impose unprecedented challenges to our society. Despite intensive research on obesity pathogenesis, an effective therapeutic strategy to treat and cure obesity is still lacking. Exciting studies in last decades have established the importance of the leptin neural pathway in the hypothalamus in the regulation of body weight homeostasis. Important hypothalamic neuropeptides have been identified as critical neurotransmitters from leptin-sensitive neurons to mediate leptin action. Recent research advance has significantly expanded the list of neurotransmitters involved in body weight-regulating neural pathways, including fast-acting neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate. Given the limited knowledge on the leptin neural pathway for body weight homeostasis, understanding the function of neurotransmitters released from key neurons for energy balance regulation is essential for delineating leptin neural pathway and eventually for designing effective therapeutic drugs against the obesity epidemic. PMID- 22058036 TI - Crystal structure of human Gadd45gamma [corrected] reveals an active dimer. AB - The human Gadd45 protein family plays critical roles in DNA repair, negative growth control, genomic stability, cell cycle checkpoints and apoptosis. Here we report the crystal structure of human Gadd45gamma [corrected], revealing a unique dimer formed via a bundle of four parallel helices, involving the most conserved residues among the Gadd45 isoforms. Mutational analysis of human Gadd45gamma [corrected] identified a conserved, highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen (PCNA), p21 and cdc2, suggesting that the parallel dimer is the active form for the interaction. Cellular assays indicate that: (1) dimerization of Gadd45gamma [corrected] is necessary for apoptosis as well as growth inhibition, and that cell growth inhibition is caused by both cell cycle arrest and apoptosis; (2) a conserved and highly acidic patch on the dimer surface, including the important residues Glu87 and Asp89, is a putative interface for binding proteins related to the cell cycle, DNA repair and apoptosis. These results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function. PMID- 22058037 TI - Structural insight into substrate specificity of human intestinal maltase glucoamylase. AB - Human maltase-glucoamylase (MGAM) hydrolyzes linear alpha-1,4-linked oligosaccharide substrates, playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity. The amino- and carboxyl-terminal portions of MGAM (MGAM-N and MGAM-C) carry out the same catalytic reaction but have different substrate specificities. In this study, we report crystal structures of MGAM-C alone at a resolution of 3.1 A, and in complex with its inhibitor acarbose at a resolution of 2.9 A. Structural studies, combined with biochemical analysis, revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites (+ 2 and + 3 subsites), accounting for the preference for longer substrates of MAGM C compared with that of MGAM-N. Moreover, we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides. These results provide important information for understanding the substrate specificity of alpha-glucosidases during the process of terminal starch digestion, and for designing more efficient drugs to control type 2 diabetes or obesity. PMID- 22058038 TI - Programmed cell death may act as a surveillance mechanism to safeguard male gametophyte development in Arabidopsis. AB - Programmed cell death (PCD) plays an important role in plant growth and development as well as in stress responses. During male gametophyte development, it has been proposed that PCD may act as a cellular surveillance mechanism to ensure successful progression of male gametogenesis, and this suicide protective machinery is repressed under favorable growth conditions. However, the regulatory mechanism of male gametophyte-specific PCD remains unknown. Here, we report the use of a TdT-mediated dUTP nick-end labeling-based strategy for genetic screening of Arabidopsis mutants that present PCD phenotype during male gametophyte development. By using this approach, we identified 12 mutants, designated as pcd in male gametogenesis (pig). pig mutants are defective at various stages of male gametophyte development, among which nine pig mutants show a microspore-specific PCD phenotype occurring mainly around pollen mitosis I or the bicellular stage. The PIG1 gene was identified by map-based cloning, and was found to be identical to ATAXIA TELANGIECTASIA MUTATED (ATM), a highly conserved gene in eukaryotes and a key regulator of the DNA damage response. Our results suggest that PCD may act as a general mechanism to safeguard the entire process of male gametophyte development. PMID- 22058040 TI - Risk factors of workplace violence at hospitals in Japan. AB - BACKGROUND: Patients and their relatives exposed to mental stress caused by hospitalization or illness might use violence against healthcare staff and interfere with quality healthcare. OBJECTIVE: The aim of this study was to investigate incidences of workplace violence and the attributes of healthcare staff who are at high risk. DESIGN: A questionnaire-based, anonymous, and self administered cross-sectional survey. SETTING: Healthcare staff (n = 11,095) of 19 hospitals in Japan. MEASUREMENTS: Incidence rates and adjusted odd ratios of workplace violence were calculated to examine the effect of attributes of healthcare staff to workplace violence by using logistic regression analysis. RESULTS: The response rate for survey completion was 79.1% (8711/11,095). Among the respondents, 36.4% experienced workplace violence by patients or their relatives in the past year; 15.9% experienced physical aggression, 29.8% experienced verbal abuse, and 9.9% experienced sexual harassment. Adjusted odds ratios of physical aggression were significantly high in psychiatric wards, critical care centers/intensive care units (ICU)/cardiac care units (CCU), long term care wards, for nurses, nursing aides/care workers, and for longer working hours. Adjusted odds ratios of verbal abuse were significantly high in psychiatric wards, long-term care wards, outpatient departments, dialysis departments, and for longer years of work experience, and for longer working hours. Adjusted odds ratios of sexual harassment were significantly high in dialysis departments, for nurses, nursing aides/care workers, technicians, therapists and females. The general ward and direct interaction with patients were common risk factors for each type of workplace violence. CONCLUSIONS: The mechanisms and the countermeasures for each type of workplace violence at those high-risk areas should be investigated. PMID- 22058039 TI - SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion. AB - Bone marrow mesenchymal stem cells (MSCs) are considered as a promising cell source to treat the acute myocardial infarction. However, over 90% of the stem cells usually die in the first three days of transplantation. Survival potential, migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment. We hypothesized that stromal-derived factor-1 (SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes. In this study, apoptosis was induced by exposure of MSCs to H(2)O(2) for 2 h. After re-oxygenation, the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation. SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor. Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio. These protective effects were partially inhibited by AMD3100, an antagonist of CXCR4.We conclude that the SDF-1/CXCR4 axis is critical for MSC survival, migration and cytokine secretion. PMID- 22058041 TI - Role of hydrogen sulfide as a gasotransmitter in modulating contractile activity of circular muscle of rat jejunum. AB - AIM: Our aim was to determine mechanisms of action of the gasotransmitter hydrogen sulfide (H(2)S) on contractile activity in circular muscle of rat jejunum. METHODS: Jejunal circular muscle strips were prepared to measure isometric contractions. Effects of sodium hydrosulfide (NaHS), a H(2)S donor, were evaluated on spontaneous contractile activity and after pre-contraction with bethanechol. L-cysteine was evaluated as an endogenous H(2)S donor. We evaluated extrinsic nerves, enteric nervous system, visceral afferent nerves, nitric oxide, K(ATP)+ and K(Ca)+ channels, and myosin light chain phosphatase on action of H(2)S using non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, L N(G)-nitro arginine (L-NNA), glibenclamide, apamin, and calyculin A, respectively, and electrical field stimulation (EFS). RESULTS: NaHS dose dependently and reversibly inhibited spontaneous and bethanechol-stimulated contractile activity (p < 0.05). L-cysteine had a dose-dependent inhibitory effect. Non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, L NNA, or apamin had no effect on contractile inhibition by NaHS; in contrast, low dose glibenclamide and calyculin A prevented NaHS-induced inhibition. We could not demonstrate H(2)S release by EFS. CONCLUSIONS: H(2)S inhibits contractile activity of jejunal circular muscle dose-dependently, in part by K(ATP)+ channels and via myosin light chain phosphatase, but not via pathways mediated by the extrinsic or enteric nervous system, visceral afferent nerves, nitric oxide, or K(Ca)+ channels. PMID- 22058042 TI - Oncologic colorectal resection, not advanced endoscopic polypectomy, is the best treatment for large dysplastic adenomas. AB - INTRODUCTION: Endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and partial circumference resection are used for large benign polyps to avoid an "Oncologic" Colorectal Resection (OCR); polyps with invasive cancer require OCR. This review of polyp patients who had OCR was done to stratify polyps into risk groups to guide treatment. METHODS: Colonoscopy, operative, and pathology reports of patients with adenoma (+/- dysplasia) who had OCR were reviewed. Polyp size, location, and pathology were assessed. RESULTS: Three hundred eighty-six polyp patients who had OCR were studied. Polyp locations were: right, 263 (68.1%); transverse, 33 (8.6%); sigmoid, 38 (9.8%); rectum, 23 (6.0%); and multiple sites, 13 (3.4%). The preoperative diagnosis was adenoma for 288 (74.6%) and dysplastic adenoma for 98 patients (25.4%). Final pathology revealed 62 invasive cancers (16.1%); 35% (34 out of 98) with dysplasia preoperatively had cancer versus 9.7% (28 out of 288) with adenoma alone (p < 0.0001). The mean lymph node count was 16.0 +/- 10.2. Cancer stage breakdown was: stage 1, 74%; stage 2, 8.1%; stage 3, 16%; and stage 4, 1.6%. The mean benign polyp size was 3.0 +/- 1.9 versus 3.9 +/- 2.4 cm for malignant polyps (p = 0.0008). CONCLUSION: Over one out of three of dysplastic polyps and 10% of adenomas were invasive cancers. OCR is advised for dysplastic polyps; ESD, EMR, and wedge resection are appropriate for non-dysplastic adenomas. PMID- 22058043 TI - Extended follow-up and outcomes of patients undergoing pancreaticoduodenectomy for nonmalignant disease. AB - BACKGROUND: Due to improved surgical outcomes and increased detection of pancreatic lesions, the resection of nonmalignant and indeterminate lesions of the pancreas has increased. AIMS: This study aims to assess the outcomes over an extended period of time and the clinical consequences of pancreaticoduodenectomy (PD) performed for nonmalignant indications. METHODS: Patients undergoing a PD between 2006 and 2010 were retrospectively identified and asked to complete a symptom survey. Charts were reviewed for hospital admissions, emergency room visits, complications, and procedures performed. RESULTS: A total of 132 patients were identified through database review with a median follow-up of 2.8 years. Forty-two patients (31.1%) completed the phone survey. Pain and diarrhea were the most common symptoms reported, negatively impacting the patient's daily life in 4.9% and 7.3% of patients, respectively. Diabetes developed or worsened in 19.5%, with new insulin required in 12.2%. Complications were rare, with abdominal abscess (7.6%) occurring most commonly. CONCLUSIONS: Although some patients experienced symptoms that negatively impacted their daily life or had diabetic issues following surgery, the outcome of patients undergoing PD for nonmalignant indications was generally favorable. Further prospective study is warranted. PMID- 22058044 TI - Stopping smoking in the weeks prior to surgery has no effect on the risk of postoperative complications. PMID- 22058045 TI - Low-magnitude high-frequency loading via whole body vibration enhances bone implant osseointegration in ovariectomized rats. AB - Osseointegration is vital to avoid long-time implants loosening after implantation surgery. This study investigated the effect of low-magnitude high frequency (LMHF) loading via whole body vibration on bone-implant osseointegration in osteoporotic rats, and a comparison was made between LMHF vibration and alendronate on their effects. Thirty rats were ovariectomized to induce osteoporosis, and then treated with LMHF vibration (VIB) or alendronate (ALN) or a control treatment (OVX). Another 10 rats underwent sham operation to establish Sham control group. Prior to treatment, hydroxyapatite (HA)-coated titanium implants were inserted into proximal tibiae bilaterally. Both LMHF vibration and alendronate treatment lasted for 8 weeks. Histomorphometrical assess showed that both group VIB, ALN and Sham significantly increased bone-to implant contact and peri-implant bone fraction (p < 0.05) when compared with group OVX. Nevertheless the bone-to-implant contact and peri-implant bone fraction of group VIB were inferior to group ALN and Sham (p < 0.05). Biomechanical tests also revealed similar results in maximum push out force and interfacial shear strength. Accordingly, it is concluded that LMHF loading via whole body vibration enhances bone-to-implant osseointegration in ovariectomized rats, but its effectiveness is weaker than alendronate. PMID- 22058046 TI - Sleep contributes to dendritic spine formation and elimination in the developing mouse somatosensory cortex. AB - Sleep is maximal during early postnatal life when rapid and extensive synapse remodeling occurs. It remains unknown whether and how sleep affects synapse development and plasticity. Using transcranial two-photon microscopy, we examined the formation and elimination of fluorescently labeled dendritic spines and filopodia of Layer 5 pyramidal neurons in the barrel cortex of 3-week-old mice during wakefulness and sleep. We observed high turnover of dendritic protrusions over 2 h in both wake and sleep states. The formation rate of dendritic spines or filopodia over 2 h was comparable between the two states. The elimination rate of dendritic spines or filopodia was lower during 2-h wakefulness than during 2-h sleep. Similar results were observed on dendritic protrusion dynamics over 12-h light/dark cycle when mice spent more time asleep or awake. The substantial remodeling of dendritic protrusions during the sleep state supports the notion that sleep plays an important role in the development and plasticity of synaptic connections in the mouse cortex. PMID- 22058047 TI - Catalytic asymmetric diastereodivergent deracemization. AB - Your wish is my command: Deracemization is a powerful strategy wherein a racemate is converted into a 100 % yield of a single enantiopure product. A new concept in catalytic deracemization is presented, in which a racemate with n stereogenic elements can be selectively converted into each one of 2(m) (m = number of chiral centers of the product) different enantiopure products, by simple tuning of the reaction conditions. PMID- 22058048 TI - Acinar Cell Carcinoma Responding to Carboplatin/Etoposide Chemotherapy. PMID- 22058049 TI - Rapid microparticle patterning by enhanced dielectrophoresis effect on a double layer electrode substrate. AB - We present a feasible dielectrophoresis (DEP) approach for rapid patterning of microparticles on a reusable double-layer electrode substrate in microfluidics. Simulation analysis demonstrated that the DEP force was dramatically enhanced by the induced electric field on top interdigitated electrodes. By adjusting electric field intensity through the bottom electrodes on thin glass substrate (100 MUm), polystyrene particles (10 MUm) were effectively patterned by top electrodes within several seconds (<5 s). The particle average velocity can reach a maximum value of about 20.0+/-3.0 MUm/s at 1 MHz with the strongest DEP force of 1.68 pN. This approach implements integration of functional electrodes into one substrate and avoids direct electrical connection to biological objects, providing a potential lab-on-chip system for biological applications. PMID- 22058050 TI - Pharmacokinetics of vitexin-4"-O-glucoside in rats after intravenous application. AB - Vitexin-4"-O-glucoside (VOG), being a main component in the leaves of Crataegus pinnatifida Bge. var. major, was isolated and then three different doses (20, 40, and 60 mg/kg) of VOG were administered intravenously to rats. To study its pharmacokinetics, a simple and rapid HPLC method was developed using hesperidin as internal standard and the relative parameters were calculated by both compartmental and non-compartmental approach. The results showed that VOG fitted a two-compartment open model. The values of AUC increased proportionally within the range of 20-60 mg/kg. Additionally, alpha half-life, beta half-life, (a)CL, MRT(0->t ), MRT(0->infinity ), and terminal half-life of VOG in rats showed significant differences between 20 mg/kg and other doses. Thereby, VOG presented a dose-dependent pharmacokinetics in the range of 20-60 mg/kg and non-linear pharmacokinetics at lower dose. PMID- 22058051 TI - The COL7A1 mutation database. AB - Dystrophic Epidermolysis Bullosa (DEB) is a genetic disease caused by mutations in the COL7A1 gene that is inherited in the autosomal dominant or recessive mode. We have developed a curated, freely accessible COL7A1 specific database (http://www.col7.info), which contains more than 730 reported and unpublished sequence variants of the gene. Molecular defects are reported according to HGVS recommendation. The clinical description module is provided with an advanced search tool together with a CSV (comm. separated values) data format download option. This compilation of COL7A1 data and nomenclature is aimed at assisting molecular and clinical geneticists to enhance the collaboration between researchers worldwide. PMID- 22058052 TI - Excess dietary iodine differentially affects thyroid gene expression in diabetes, thyroiditis-prone versus -resistant BioBreeding (BB) rats. AB - SCOPE: To identify genes involved in the susceptibility to iodine-induced autoimmune thyroiditis. METHODS AND RESULTS: Diabetes, thyroiditis-prone (BBdp) and -resistant (BBc) rats were fed either a control or a high-iodine diet for 9 wk. Excess iodine intake increased the incidence of insulitis and thyroiditis in BBdp rats. BBdp rats fed the high-iodine diet that did not develop thyroiditis had higher mRNA levels of Fabp4, Cidec, perilipin, Ppargamma and Slc36a2 than BBdp rats fed the control diet and BBc rats fed either the control or the high iodine diet. BBdp rats fed the high-iodine diet that did develop thyroiditis had higher mRNA levels of Cidec, Icam1, Ifitm1, and Slpi than BBdp rats fed the control diet and BBc rats fed either the control or the high-iodine diet. BBdp rats that did develop thyroiditis had lower mRNA levels of Fabp4, perilipin and Slc36a2 but higher mRNA levels of Icam1, Ifitm1 and Slpi than BBdp that did not develop thyroiditis. Excess dietary iodine also increased the protein levels of Fabp4, Cidec and perilipin in BBdp rats. CONCLUSION: Differential expression of thyroid genes in BBdp versus BBc rats caused by excess dietary iodine may be implicated in autoimmune thyroiditis and insulitis pathogenesis. PMID- 22058053 TI - Methods to assess neuroinflammation. AB - Neuroinflammation is observed in many brain pathologies: in neurodegenerative diseases and multiple sclerosis as well as in chemically induced lesions. It is characterized by the reactivity of microglial cells and astrocytes, activation of inducible NO-synthase (i-NOS), and increased expression and/or release of cytokines and chemokines. Clearly, cell-to-cell signaling between the different brain cell types plays an important role in the initiation and propagation of neuroinflammation, but despite the growing list of known molecular actors, the underlying pathways and the sequence of events remain to be fully elucidated. The present chapter presents an example of how to assess neuroinflammation in complex brain tissues, using aggregating brain cell cultures as an in vitro model. This three-dimensional cell culture system provides optimal cell-to-cell interactions crucial for histotypic cellular maturation and control of neuroinflammatory processes. The techniques described here comprise immunocytochemistry to assess the reactivity of microglia and astrocytes and the expression of cytokines; quantitative RT-PCR to measure the mRNA expression of cytokines (TNF-alpha, IL 1beta, IL-6, IL-1ra, TGF-beta, IL-15, IFN-gamma), chemokines (ccl5, cxcl1, cxcl2), and i-NOS; and immunoblotting to assess MAP kinase pathway activation (phosphorylation of p38 and p44/42 MAP kinases). PMID- 22058054 TI - Murine embryonic stem cell derivation, in vitro pluripotency characterization, and in vivo teratoma formation. AB - The derivation of embryonic stem (ES) cells represents one of the most important breakthroughs in mammalian developmental biology. In addition to their utility in a wide array of in vitro studies, ES cells are also one of the most useful starting materials for the generation of mutants by homologous recombination in mice (Thomson and Solter, 1988). When ES cells are injected into host blastocysts and transferred to the uterus of a pseudo-pregnant mouse, they can contribute to different types of tissues in chimeric mice, including the germ line (Bradley et al., 1984). Hundreds of genes have been studied through genetic manipulation of ES cells to model human genetic diseases. In this unit, the ES cell lines are derived from the 129SvEv mice strain, which has a high probability of promoting germ line transmission. Procedures for validating and characterizing ES cell pluripotency are also described in detail. PMID- 22058055 TI - Preparation of epithelial and mesenchymal stem cells from murine mammary gland. AB - The mammary gland is a complex organ consisting of multiple cell types that undergo extensive remodeling during pregnancy and involution, cyclical changes that suggest the existence of a resident stem cell population that is responsible for remarkable tissue regeneration. The basic functional unit of the mammary gland is the terminal duct lobular unit, which invades the stromal tissue (fat, connective tissue, blood vessels, etc.). Luminal epithelial cells line the ducts while outer myoepithelial cells secrete the basal lamina that separates the mammary gland parenchyma from the mesenchymal cells of the stroma. Within the epithelial cell population of the ducts resides the mammary gland stem cells and it is believed that this population is the origin of the mammary gland cancer stem cells as well. In the mouse, epithelial stem cells can be separated from mesenchymal cells on the basis of CD24, CD44, and CD49f expression. This allows for the determination of both normal and cancer stem cell potential of these two populations and permits investigation into their interaction in tumor development. PMID- 22058056 TI - Human platelet-rich plasma stimulates migration and chondrogenic differentiation of human subchondral progenitor cells. AB - In cartilage repair, platelet-rich plasma (PRP) is used in one-step approaches utilizing microfracture and matrix-induced chondrogenesis procedures, bone marrow derived cell transplantation, or intra-articular injection. The aim of our study was to evaluate the effect of human PRP on the migration and chondrogenic differentiation of human subchondral progenitors. Human progenitors were derived from subchondral cortico-spongious bone (CSP), were analyzed for their migration capacity upon PRP treatment in 96-well chemotaxis assays and cultured in high density pellet cultures under serum-free conditions in the presence of 5% PRP. Chemotaxis assays showed that 0.1-100% PRP significantly (p < 0.05) stimulate the migration of CSP compared to untreated controls. Histological staining of proteoglycan and immuno-staining of type II collagen indicated that progenitors stimulated with PRP show significantly increased cartilage matrix formation compared to untreated progenitors. Real-time gene expression analysis of typical chondrocyte marker genes as well as osteogenic and adipogenic markers like osteocalcin and fatty acid binding protein showed that PRP induces the chondrogenic differentiation sequence of human progenitors in high-density pellet cultures, while osteogenic or adipogenic differentiation was not evident. These results suggest that human PRP may enhance the migration and stimulate the chondrogenic differentiation of human subchondral progenitor cells known from microfracture. PMID- 22058057 TI - Review: more research needed on early intervention for psychosis. PMID- 22058058 TI - Zebrafish neurobiology: from development to circuit function and behaviour. PMID- 22058059 TI - The interleukin-10-1082 promoter polymorphism and cancer risk: a meta-analysis. AB - Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and anti-angiogenic properties and play an important role in the pathogenesis of cancer. IL-10-1082A>G polymorphism is the most extensively studied polymorphism in the IL-10 gene in cancer susceptibility. To date, a number of case-control studies were conducted to investigate the association between IL-10-1082A>G polymorphism and cancer risk in humans. However, the association between the IL 10-1082A>G polymorphism and cancer risk is still ambiguous. In an effort to solve this controversy, we performed a meta-analysis based on 61 case-control studies, including 14,499 cancer cases and 16,967 controls. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. In the stratified analyses by specific cancer type, increased risk was found in lung cancer (OR = 3.16, 95% CI = 1.16-8.63 for GA versus AA; OR = 2.07, 95% CI = 1.16 3.70 for GG versus AA; OR = 3.17, 95% CI = 1.31-7.68 for GA/GG versus AA) and non Hodgkin's lymphoma (OR = 1.18, 95% CI = 1.02-1.36 for GA versus AA; OR = 1.17, 95% CI = 1.02-1.35 for GA/GG versus AA). The meta-analysis also indicated that the variant genotypes were associated with a moderately increased risk in Asians in all genetic models (OR = 1.80, 95% CI = 1.17-2.76 for GA versus AA; OR = 3.32, 95% CI = 1.62-6.82 for GG versus AA; OR = 1.67, 95% CI = 1.07-2.60 for GA/GG versus AA; OR= 2.93, 95% CI = 1.43-6.03 for GG versus AA/GA). The meta-analysis suggested that the IL-10-1082A>G polymorphism was associated with increased risk of cancer in Asians and lung cancer and non-Hodgkin's lymphoma. To draw comprehensive and true conclusions, more researches with larger numbers of worldwide participants are needed to examine associations between IL-10-1082A>G polymorphism and cancer risk. PMID- 22058060 TI - A unique bicyclic monosaccharide from the Bradyrhizobium lipopolysaccharide and its role in the molecular interaction with plants. AB - Sugar coat: The nitrogen-fixing soil bacterium Bradyrhizobium sp. BTAi1 is coated with a unique lipopolysaccharide that does not induce innate immune responses in its host plant Aeschynomene indica or in different plant families. The chemical nature of the monosaccharide forming the polymer (see picture) is unprecedented in nature, which helps to avoid "harmful" recognition by its symbiotic host. PMID- 22058062 TI - Identification of human herpesviruses 1 to 8 in Tunisian multiple sclerosis patients and healthy blood donors. AB - Members of the human Herpesviridae family are candidates for representing the macroenvironmental factors associated with multiple sclerosis (MS) pathogenesis. To verify the possible role of human herpesviruses (HHVs) as triggering or aggravating factors in relapsing-remitting multiple sclerosis clinical outcome, we studied the prevalence of all eight human herpesviruses in whole blood samples collected from 51 MS patients and from 51 healthy controls. The presence of DNA of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7) and human herpesvirus 8 (HHV-8) was searched by specific nested polymerase chain reaction. HHVs were significantly more prevalent in the blood of MS patients than in those of the controls (P < 10( 4)). HSV-1, HSV-2, HCMV and HHV-8 were negative in both MS patients and controls samples. In MS patients, EBV, HHV-7, HHV-6 and VZV were detected in 31.3%, 33.3%, 5.8% and 7.8% of samples, respectively, compared with 3.9%, 9.8%, 1.96% and 1.96%, respectively, of samples from controls. We found a statistically significant difference only for EBV DNA and for HHV-7 DNA prevalence (P < 0.001 and P = 0.03). Although these results indicate lack of apparent association in terms of gender, type of diagnosis, symptoms, disease score and beta interferon treatment between EBV or HHV-7 to MS among Tunisian patients, heterogeneity related to genetic polymorphism as well as geographical distribution of the disease and of pathogens may be of significance. PMID- 22058061 TI - CSF biomarkers for amyloid and tau pathology in Alzheimer's disease. AB - Reliable biomarkers for Alzheimer's disease (AD) are highly needed in the clinic. As a fluid surrounding the brain and reflecting the major neuropathological features characteristic to the AD brain, the cerebrospinal fluid (CSF) provides the natural source for AD biomarkers. The expected use of an ideal AD biomarker is for the following purposes: (1) diagnosis, (2) prediction, (3) monitoring of disease progression, and (4) drug discovery. Review of the literature revealed that CSF analysis, specifically amyloid-beta (Abeta42, total (T)-tau, and phosphorylated (P)-tau, are reliable markers for AD diagnosis, even at very early stages, particularly vs. healthy controls, while more limited evidence for distinguishing from other dementias. As for prediction, abnormal CSF markers are predictors of cognitive decline in healthy subjects, converting from MCI to development of AD, and of the rate of cognitive decline in mild AD. Regarding monitoring disease progression, the use of CSF biomarkers does not seem very promising since a comparison of the marker levels between baseline and following years of follow-up revealed a remarkable stability of biomarker levels in CSF. As for the use in drug discovery, it is estimated that using CSF markers for the selection of subjects for clinical trials may reduce robustly sample size and trial costs. Yet, since no effective drug is currently available, the contribution of CSF AD biomarkers in drug discovery cannot be currently fully assessed. Nevertheless, testing CSF for evidence of CNS inflammation may help safety monitoring in AD clinical trials. Factors affecting CSF biomarker levels that should be taken into account are assay variability as well as effects of age, gender, apoE and other genetic variations, education, and time of day. Much effort has been and is still being dedicated into developing and validating CSF AD biomarkers by many centers in the world. Identifying additional CSF components, reflecting not only the lesions characteristic to AD (plaques and tangles) but also more functional and structural brain parameters, may provide a wider profile of the changes taking place in AD brains, and be further used as reliable CSF biomarkers for AD monitoring. PMID- 22058063 TI - A comparative study of interfaces for microchip micellar electrokinetic chromatography-electrospray ionization mass spectrometry using the surfactant ammonium dodecyl sulfate. AB - Using ammonium dodecyl sulfate (ADS) as the surfactant, the response of three common interfaces in the direct coupling of microchip micellar electrokinetic chromatography with electrospray ionization mass spectrometry was studied. In the range of 10-40 mM surfactant, a conventional sheath liquid interface provided poorer sensitivity than both sheathless interface and low-sheath-flow interface. At a surfactant concentration <20 mM, a low-sheath-flow interface exhibited less sensitivity than a sheathless interface; however, it outperformed the sheathless interface above a concentration of 20 mM. At a surfactant concentration above 20 mM, signal reduction due to dilution of the analyte compensated by signal enhancement gained from a reduction in ion suppression effect. The difference in responses of the interfaces was mainly due to the dilution effect, whereas the effect of flow rate became an important factor when the difference in responses between the interfaces was not significant. The utility of the PMMA microchip MEKC/MS using a low-sheath-flow interface was demonstrated by the analysis of sulfonamides at a concentration of 40 mM. The interday precision was in the range of 4.9-14.5%, and the LOD was in the range of 0.34-1.03 ng/mL (MEKC/MS/MS). PMID- 22058064 TI - Chronic family stress interacts with 5-HTTLPR to predict prospective depressive symptoms among youth. AB - BACKGROUND: Previous research, predominantly with adults, has shown that the serotonin transporter gene (5-HTTLPR) interacts with stress (G * E) to predict depressive symptoms; however, few G * E studies have been conducted with youth using rigorous methods, particularly a prospective design and contextual interview to assess stress. This study examined the interaction between 5-HTTLPR and stress, both chronic and episodic, to predict longitudinal change in depressive symptoms among children and adolescents. METHODS: A general community sample of youth (N = 200; 57% girls; mean age: 12.09 years old) was genotyped for 5-HTTLPR (rs 25531) at baseline. They were interviewed via contextual stress procedures to ascertain chronic family stress and episodic stressors and completed depressive symptoms questionnaires at baseline and 6 months later. RESULTS: A significant G * E showed that chronic family stress predicted prospective increases in depressive symptoms over 6 months among youth possessing the high-risk S allele. This G * E was not found for episodic stressors occurring in the last 6 months. There was no moderation by sex or pubertal status. CONCLUSIONS: These findings advance knowledge on G * E effects in depression among youth. This is the first study to show that chronic family stress, but not episodic stressors, when ascertained by rigorous stress interview, interacts with 5-HTTLPR to prospectively predict depressive symptoms among children and adolescents. PMID- 22058065 TI - Prebiotic effects and intestinal fermentation of cereal arabinoxylans and arabinoxylan oligosaccharides in rats depend strongly on their structural properties and joint presence. AB - SCOPE: Cereal arabinoxylan (AX) is one of the main dietary fibers in a balanced human diet. To gain insight into the importance of structural features of AX for their prebiotic potential and intestinal fermentation properties, a rat trial was performed. METHODS AND RESULTS: A water unextractable AX-rich preparation (WU-AX, 40% purity), water extractable AX (WE-AX, 81% purity), AX oligosaccharides (AXOS, 79% purity) and combinations thereof were included in a standardized diet at a 5% AX level. WU-AX was only partially fermented in the ceco-colon and increased the level of butyrate and of butyrate producing Roseburia/E. rectale spp. Extensive fermentation of WE-AX and/or AXOS reduced the pH, suppressed relevant markers of the proteolytic breakdown and induced a selective bifidogenic response. Compared with WE-AX, AXOS showed a slightly less pronounced effect in the colon as its fermentation was virtually complete in the cecum. Combining WU-AX and AXOS caused a striking synergistic increase in cecal butyrate levels. WU-AX, WE-AX and AXOS together combined a selective bifidogenic effect in the colon with elevated butyrate levels, a reduced pH and suppressed proteolytic metabolites. CONCLUSION: The prebiotic potential and fermentation characteristics of cereal AX depend strongly on their structural properties and joint presence. PMID- 22058066 TI - Sucrose in aqueous solution revisited, Part 2: adaptively biased molecular dynamics simulations and computational analysis of NMR relaxation. AB - We report 100 ns molecular dynamics simulations, at various temperatures, of sucrose in water (with concentrations of sucrose ranging from 0.02 to 4M), and in a 7:3 water-DMSO mixture. Convergence of the resulting conformational ensembles was checked using adaptive-biased simulations along the glycosidic Phi and psi torsion angles. NMR relaxation parameters, including longitudinal (R1) and transverse (R2) relaxation rates, nuclear Overhauser enhancements (NOE), and generalized order parameter (S2) were computed from the resulting time correlation functions. The amplitude and time scales of molecular motions change with temperature and concentration in ways that track closely with experimental results, and are consistent with a model in which sucrose conformational fluctuations are limited (with 80-90% of the conformations having phi-psi values within 20 degrees of an average conformation), but with some important differences in conformation between pure water and DMSO-water mixtures. PMID- 22058067 TI - Variation in initial kidney replacement therapy for end-stage renal disease due to lupus nephritis in the United States. AB - OBJECTIVE: Little is known about the patterns of use of initial kidney replacement therapies among patients with lupus nephritis (LN) end-stage renal disease (ESRD). We aimed to identify sociodemographic and clinical factors associated with variation in initial kidney replacement therapies among LN ESRD patients. METHODS: Patients with incident LN ESRD (1995-2006) were identified in the US Renal Data System. Age, sex, race, ethnicity, medical insurance, employment status, residential region, clinical factors, and comorbidities were considered as potential predictors of ESRD treatment choice, i.e., peritoneal dialysis (PD), hemodialysis (HD), or preemptive kidney transplantation in age adjusted and multivariable-adjusted logistic regression analyses. RESULTS: Of the 11,317 individuals with incident LN ESRD, 82.0% initiated HD, 12.2% initiated PD, and 2.8% underwent preemptive kidney transplantation. Receiving initial PD was significantly associated with earlier calendar year, female sex, higher albumin and hemoglobin levels, and lower serum creatinine levels. African Americans (versus whites), Medicaid beneficiaries and those with no health insurance (versus private insurance), and those unemployed (versus employed) had significantly reduced PD initiation. Comorbidities including congestive heart failure, peripheral vascular disease, and the inability to ambulate were also associated with decreased PD. Many sociodemographic and clinical factors favoring PD were associated with preemptive kidney transplant (versus dialysis) as well. CONCLUSION: Few patients with LN ESRD receive initial PD or preemptive kidney transplantation. Race, ethnicity, employment, and medical insurance type are strongly associated with initial kidney replacement therapy choice. Future studies need to investigate the appropriateness of sociodemographic and clinical variation and the comparative effectiveness of kidney replacement therapies for LN ESRD. PMID- 22058068 TI - Selective artificial transmembrane channels for protons by formation of water wires. AB - Lined up water molecules: Artificial transmembrane channels from pillar[5]arene monomeric and dimeric derivatives have been prepared. Single-channel conductance measurements and isotope effect experiments under acidic conditions showed selective proton transport through the channels, which were mediated by water wires formed in the pillar[5]arene backbones (see picture). PMID- 22058070 TI - Microwave-assisted synthesis of colloidal inorganic nanocrystals. AB - Colloidal inorganic nanocrystals stand out as an important class of advanced nanomaterials owing to the flexibility with which their physical-chemical properties can be controlled through size, shape, and compositional engineering in the synthesis stage and the versatility with which they can be implemented into technological applications in fields as diverse as optoelectronics, energy conversion/production, catalysis, and biomedicine. The use of microwave irradiation as a non-classical energy source has become increasingly popular in the preparation of nanocrystals (which generally involves complex and time consuming processing of molecular precursors in the presence of solvents, ligands and/or surfactants at elevated temperatures). Similar to its now widespread use in organic chemistry, the efficiency of "microwave flash heating" in dramatically reducing overall processing times is one of the main advantages associated with this technique. This Review illustrates microwave-assisted methods that have been developed to synthesize colloidal inorganic nanocrystals and critically evaluates the specific roles that microwave irradiation may play in the formation of these nanomaterials. PMID- 22058071 TI - Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism. AB - SCOPE: Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Stains are widely prescribed to lower cholesterol levels, but natural dietary compounds may also be effective. Therefore, we studied the effect of the natural dietary compound curcumin on atherosclerosis and its underlying mechanisms based on plasma and hepatic lipid metabolism. METHODS AND RESULTS: LDLR(-/-) mice were fed a high-cholesterol diet and treated with curcumin, lovastatin or control (n=10 per group) for 18 wk. Aortic arch sections revealed curcumin ameliorated early atherosclerotic lesions, lipid infiltration, ICAM-1 and VCAM-1 localization, similar to lovastatin treatment. Furthermore, curcumin lowered plasma cholesterol, triglycerides, LDL cholesterol and Apo B levels as well as CETP activity, while curcumin increased plasma HDL cholesterol and liver Apo A-I expression, similar to lovastatin treatment. Curcumin caused transcriptional inhibition of HMG-CoA reductase, independent of ACAT1 and ACAT2 expression. Hepatic PPARalpha and LXRalpha expression was upregulated by curcumin treatment. Hepatic complement factor D (Cfd) and systemic CRP levels, markers of immune complement pathway activation, were significantly reduced by curcumin treatment. CONCLUSION: Long-term curcumin treatment lowers plasma and hepatic cholesterol and suppresses early atherosclerotic lesions comparable to the protective effects of lovastatin. The anti-atherogenic effect of curcumin is mediated via multiple mechanisms including altered lipid, cholesterol and immune gene expression. PMID- 22058072 TI - Effects of maternal food restriction on offspring lung extracellular matrix deposition and long term pulmonary function in an experimental rat model. AB - Intrauterine growth restriction (IUGR) increases the risk of respiratory compromise throughout postnatal life. However, the molecular mechanism(s) underlying the respiratory compromise in offspring following IUGR is not known. We hypothesized that IUGR following maternal food restriction (MFR) would affect extracellular matrix deposition in the lung, explaining the long-term impairment in pulmonary function in the IUGR offspring. Using a well-established rat model of MFR during gestation to produce IUGR pups, we found that at postnatal day 21, and at 9 months (9M) of age the expression and abundance of elastin and alpha smooth muscle actin (alphaSMA), two key extracellular matrix proteins, were increased in IUGR lungs when compared to controls (P < 0.05, n = 6), as determined by both Western and immunohistochemistry analyses. Compared to controls, the MFR group showed no significant change in pulmonary resistance at baseline, but did have significantly decreased pulmonary compliance at 9M (P < 0.05 vs. control, n = 5). In addition, MFR lungs exhibited increased responsiveness to methacholine challenge. Furthermore, exposing cultured fetal rat lung fibroblasts to serum deprivation increased the expression of elastin and elastin-related genes, which was blocked by serum albumin supplementation, suggesting protein deficiency as the predominant mechanism for increased pulmonary elastin deposition in IUGR lungs. We conclude that accompanying the changes in lung function, consistent with bronchial hyperresponsiveness, expression of the key alveolar extracellular matrix proteins elastin and alphaSMA increased in the IUGR lung, thus providing a potential explanation for the compromised lung function in IUGR offspring. PMID- 22058073 TI - Photoactivatable caged cyclic RGD peptide for triggering integrin binding and cell adhesion to surfaces. AB - We report the synthesis and properties of a photoactivatable caged RGD peptide and its application for phototriggering integrin- and cell-binding to surfaces. We analysed in detail 1) the differences in the integrin-binding affinity of the caged and uncaged forms by quartz crystal microbalance (QCM) studies, 2) the efficiency and yield of the photolytic uncaging reaction, 3) the biocompatibility of the photolysis by-products and irradiation conditions, 4) the possibility of site, temporal and density control of integrin-binding and therefore human cell attachment, and 5) the possibility of in situ generation of cell patterns and cell gradients by controlling the UV exposure. These studies provide a clear picture of the potential and limitations of caged RGD for integrin-mediated cell adhesion and demonstrate the application of this approach to the control and study of cell interactions and responses. PMID- 22058074 TI - A kangaroo and your research toolbox. PMID- 22058075 TI - Hardening of the nanoparticle-protein corona in metal (Au, Ag) and oxide (Fe3O4, CoO, and CeO2) nanoparticles. AB - The surface modifications of metal and metal oxide nanoparticles with sizes ranging from 7 to 20 nm dispersed in commonly used cell culture medium supplemented with serum are investigated. All the tested nanoparticles adsorb proteins onto their surface, thereby forming a protein corona through a dynamic process evolving towards an irreversible coating (hard protein corona). Despite the fact that the studied nanomaterials have similar characteristics of hydrophobicity and surface charge, different temporal patterns of the protein corona formation are observed that can be considered a fingerprint for nanoparticle identification. Some of the biological and toxicological implications of the formation of the nanoparticle-protein corona are studied using the human monocytic cell line THP-1 exposed to cobalt oxide nanoparticles. Results show that production of reactive oxygen species is decreased if the nanoparticles are preincubated for 48 h with serum. PMID- 22058076 TI - Evaluation of association between exercise-induced bronchoconstriction and childhood asthma control test questionnaire scores in children. AB - OBJECTIVE: Asthma control represents a major challenge in the management of asthmatic children; however, correct perception of control is poor. The aim of the study was to evaluate the association between subjective answers given to the Childhood Asthma Control Test (C-ACT) and objective evaluation of exercise induced bronchonstriction (EIB) by standardized treadmill exercise challenge. METHODS: EIB was evaluated by standardized treadmill exercise challenge and related to C-ACT scores in 92 asthmatic children. RESULTS: Of the 92 studied children only six children had a concordance between a positive challenge test (DeltaFEV1 >= 13%) and a positive response to the exercise-related issue of the C ACT questionnaire (C-ACT total score <= 19). There was no significant association between the degree of EIB and the scores relative to the single question on exercise-related problems while a significant association was found when considering the whole questionnaire with C-ACT total score > 19 (r = -0.40, P < 0.001). The two single questions showing a significant association were those focusing on nocturnal asthma. The areas under the ROC curve (AUC) for the sum of the scores of these questions in relationship to a positive response to the exercise test was 0.74. The AUC of the C-ACT total score was 0.76 and 0.55 for the specific question on EIB related problems. CONCLUSION: The discrimination power of the C-ACT total score in relationship to EIB was moderately good, and C ACT questionnaire was capable of correctly predicting the absence of EIB in children reporting a global score > 19. However, direct questions on EIB are associated with a high number of false positive and negative responses; better associations are found questioning on the presence on nocturnal symptoms. PMID- 22058077 TI - Bottom-up preparation of porous metal-oxide ultrathin sheets with adjustable composition/phases and their applications. AB - A facile bottom-up synthesis approach is developed to prepare porous metal-oxide ultrathin sheets, e.g., SnO(2), Fe(2)O(3), and SnO(2)-Fe(2)O(3), with thicknesses of ~5 nm. Graphene sheets are used as the sacrificing template. Such a process can be extended to the synthesis of multiphased porous metal-oxide thin sheets. These porous thin sheets show interesting applications as gas sensors, effective platforms for matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, and supercapacitors. PMID- 22058078 TI - A TLR5 (g.1174C > T) variant that encodes a stop codon (R392X) is associated with bronchopulmonary dysplasia. AB - Current evidence supports a major role for inherited factors in determining bronchopulmonary dysplasia (BPD) susceptibility. The Toll-like receptor (TLR) family of proteins maintain pulmonary homeostasis in the developing lung by aiding pathogen recognition and clearance, regulating inflammation, and facilitating reparative tissue growth. We hypothesized that sequence variation in the TLR pathway genes would alter the susceptibility/severity of BPD in preterm infants. Very low birth-weight infants were recruited prospectively in a multi center study involving collection of blood samples and clinical information. Nine TLR pathway single-nucleotide polymorphisms were genotyped using a multiplexed single-base extension assay. BPD outcomes were compared among infants with and without the variant allele using Chi-square or Fisher's exact tests. In our cohort (n = 289), 66 (23.6%) infants developed BPD, out of which 32 (11.2%) developed severe BPD. The TLR5 (g.1174C > T) variant was associated with BPD (P = 0.03) and severe BPD (P = 0.004). The TIRAP (g.2054C > T) variant was associated with BPD (P = 0.04). Infants heterozygous for the X-linked IRAK1 (g.6435T > C) variant had a lower incidence of BPD compared to infants homozygous for either the reference or variant allele (P = 0.03). In regression models that controlled for potential epidemiological confounders, the TIRAP variant was associated with BPD, and the TLR5 variant was associated with severe BPD. Our data support the hypothesis that aberrant pathogen recognition in premature infants arising from TLR pathway genetic variation can contribute to BPD pathogenesis. PMID- 22058079 TI - Prevalence of cardiovascular disease risk amongst the population eligible for the NHS Health Check Programme. AB - BACKGROUND: The National Health Service (NHS) Health Check Programme aims to identify and manage patients in England aged 40-74 years with a 10-year cardiovascular disease (CVD) risk score over 20%. We aimed to assess the prevalence of high CVD risk in the English population, using the two CVD risk scores and the 20% cut off mandated in national policy, and the prevalence of risk factors within this population. DESIGN: Modelling study using patients registered in general practice in England. METHODS: Using data from the Health Survey for England, we modelled the prevalence of high CVD risk in general practice populations. RESULTS: Of those eligible for an NHS Health Check, 10.5% (2,012,000) had a risk score greater than 20% using the QRISK2 risk score; 22.0% (4,267,000) using Joint British Societies' (JBS2) score. There was a median of 206 (range 0-1693) and 447 (0-3321) patients per practice at high risk respectively, with wide geographic variation. Within the high-risk population, there was a high prevalence of CVD risk factors; in the QRISK2 population, for example 82.6% were physically inactive. To reduce risk in those at high CVD risk, we estimate the total costs of the Programme to be L176 million using QRISK2 or L378 million using JBS2. CONCLUSIONS: A large number of high-risk patients will be identified by the Programme; health service commissioners must ensure the adequate provision and the targeted allocation of risk reduction services for the Programme to be effective. The NHS must consider whether extra costs using JBS2 are warranted. The Programme must be fully monitored to ensure its cost effectiveness and appropriate outcomes such as the numbers at high risk assessed. PMID- 22058080 TI - Robust depth-based estimation in the time warping model. AB - In functional data analysis, the time warping model aims at representing a set of curves exhibiting phase and amplitude variation with respect to a common continuous process. Many biological processes, when observed across the time among different individuals, fit into this concept. The observed curves are modeled as the composition of an "amplitude process," which governs the common behavior, and a "warping process" that induces time distortion among the individuals. We aim at characterizing the first one. Because of the phase variation present among the curves, classical sample statistics computed on the observed sample provide poor representations of the amplitude process. Existing methods to estimate the mean behavior of the amplitude process consist on aligning the curves, that is, eliminating time variation, before estimation. However, since they rely on the use of sample means, they are very sensitive to the presence of outliers. In this article, we propose the use of a functional depth-based median as a robust estimator of the central behavior of the amplitude process. We investigate its properties in the time warping model, and we evaluate its performance in different simulation studies where we compare it to existing estimators, and we show its robustness against atypical observations. Finally, we illustrate its use with real data on a yeast time course microarray data set. PMID- 22058081 TI - Fatal and non-fatal adverse events of glucocorticoid therapy for Graves' orbitopathy: a questionnaire survey among members of the European Thyroid Association. AB - OBJECTIVE: The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO). DESIGN: A questionnaire-based survey among members of the European Thyroid Association (ETA) who treat GO. RESULTS: A response was obtained from 128 ETA members of which 115 used GC therapy for GO. The majority of respondents (83/115, 72%) used intravenous (i.v.) GC, with a relatively wide variety of therapeutic regimens. The cumulative dose of methylprednisolone ranged between 0.5 and 12 g (median 4.5 g) for i.v.GC and between 1.0 and 4.9 g (median 2.4 g) for oral GC. Adverse events were often reported during oral GCs (26/32, 81%); most side effects were non-severe, but ten respondents reported severe adverse events (hepatic, cardiovascular, and cerebrovascular complications), including two fatal cases, both receiving a total of 2.3 g prednisone. Adverse events were less common in i.v.GC (32/83 respondents, 39%), but mostly consisted of severe events, including seven fatal cases. All but one fatal event occurred in cumulative i.v.GC doses (>8 g) higher than those currently recommended. CONCLUSIONS: GCs are preferentially administered i.v. for the treatment of GO in Europe. Both oral and i.v.GC may be associated with severe adverse effects, including fatal cases, which are more frequently reported in daily or alternate day i.v.GC. IvGC therapy should be undertaken in centers with appropriate expertise. Patients should be carefully examined for risk factors before treatment and monitored for side effects, which may be asymptomatic, both during and after treatment. PMID- 22058082 TI - 3D self-assembled plasmonic superstructures of gold nanospheres: synthesis and characterization at the single-particle level. AB - The synthesis of 3D self-assembled plasmonic superstructures of gold nanospheres as well as the characterization of their structural and optical properties at the single-particle level is presented. This experimental work is complemented by FEM (finite element method) simulations of elastic scattering spectra and the spatial |E|(4) distribution for establishing structure-activity correlations in these complex 3D nanoclusters. PMID- 22058083 TI - Diffusion of bacteriophages through artificial biofilm models. AB - The simple two-chamber diffusion method was improved to study the diffusion properties of bacteriophage (phage) T4 through a model biofilm agarose gel membrane (AGM) embedded with dead host Escherichia coli K12 cells. The apparent diffusion coefficient (D(app) ) of phage T4 was calculated to be 2.4 * 10(-12) m(2) /s in 0.5% AGM, which was lower than the coefficient of 4.2 * 10(-12) m(2) /s in 0.5% AGM without host cells. The phage adsorption process by dead host cells slowed the apparent phage diffusion. The Langmuir adsorption equation was used to simulate phage adsorption under different multiplicity of infections (MOIs); the maximum adsorbed phage MOI was calculated to be 417 PFU/CFU, and the Langmuir adsorption constant K(L) was 6.9 * 10(-4) CFU/PFU. To evaluate the effects of phage proliferation on diffusion, a simple syringe-based biofilm model was developed. The phage was added into this homogenous biofilm model when the host cells were in an exponential growth phase, and the apparent diffusion coefficient was greatly enhanced. We concluded that D(app) of phages through biofilms could be distinctly affected by phage adsorption and proliferation, and that the idea of D(app) and these methods can be used to study diffusion properties through real biofilms. PMID- 22058084 TI - Incorporating neutralizing antibody assays into routine clinical practice: a long and arduous road. PMID- 22058085 TI - Multiple sclerosis and depression. AB - Clinically significant depression can affect up to 50% of patients with multiple sclerosis over the course of their lifetime. It is associated with an increased morbidity and mortality and is regarded by patients as one of the main determinants of their quality of life. This review summarizes current perspectives relating to diagnosis, the utility of self report screening questionnaires, warning signs of suicidal intent and the biological and psychosocial variables implicated in mood change. In particular, the association between depression and structural brain abnormalities, including those derived from diffusion tensor imaging, is highlighted. Depression is treatable, as the results from randomized controlled trials of antidepressant medication, cognitive behavior therapy and mindfulness therapy, reveal. These positive findings are offset by data showing that depression in a neurological setting is often overlooked and under treated. PMID- 22058086 TI - Rationale, challenges, and participants in a Phase II trial of a botanical product for chronic hepatitis C. AB - BACKGROUND: Chronic hepatitis C is associated with significant morbidity and mortality as a consequence of progression to cirrhosis, hepatocellular carcinoma, and liver failure. Current treatment for chronic hepatitis C with pegylated interferon (IFN) and ribavirin is associated with suboptimal responses and numerous adverse effects. A number of botanical products have been used to treat hepatic disorders. Silymarin, extracted from the milk thistle plant, Silybum marianum (L) Gaertn. (Asteraceae), has been most widely used for various liver disorders, including chronic hepatitis C, B, and alcoholic liver disease. However, the safety and efficacy of silymarin have not been studied systematically in chronic hepatitis C. PURPOSE: We describe our strategy for a phased approach for studying the impact of silymarin in hepatitis C, in the context of the unique challenges of botanical product clinical trials and the development of specific and curative antiviral therapy. METHODS: This multicenter, randomized, double-masked, placebo-controlled trial was conducted with four clinical centers and a data-coordinating center in the United States, to assess the impact of silymarin therapy in patients with chronic hepatitis C who failed conventional antiviral therapy. RESULTS: Key aspects relevant to performing clinical trials of botanical products include early identification of an appropriate product with standard product chemistry, acquisition of pharmacokinetic and dosing information, selection of the appropriate study group, and choosing rigorous outcome variables. POTENTIAL LIMITATIONS: Trial participants were chronic hepatitis C patients who were nonsustained virologic responders to IFN-based therapy; therefore, the findings are not generalizable to all hepatitis C populations. Further, alanine aminotransferase, a biochemical liver test, rather than hepatitis viral RNA or liver histology was the primary end point. CONCLUSIONS: The challenges identified and addressed during development of this United States multicenter Phase II trial to evaluate silymarin for treatment of patients with chronic hepatitis C infection who had failed to respond successfully to previous IFN-based therapy are common and must be addressed to conduct rigorous trials of botanical products. PMID- 22058087 TI - Searching for the main anti-bacterial components in artificial Calculus bovis using UPLC and microcalorimetry coupled with multi-linear regression analysis. AB - The fingerprints of artificial Calculus bovis extracts from different solvents were established by ultra-performance liquid chromatography (UPLC) and the anti bacterial activities of artificial C. bovis extracts on Staphylococcus aureus (S. aureus) growth were studied by microcalorimetry. The UPLC fingerprints were evaluated using hierarchical clustering analysis. Some quantitative parameters obtained from the thermogenic curves of S. aureus growth affected by artificial C. bovis extracts were analyzed using principal component analysis. The spectrum effect relationships between UPLC fingerprints and anti-bacterial activities were investigated using multi-linear regression analysis. The results showed that peak 1 (taurocholate sodium), peak 3 (unknown compound), peak 4 (cholic acid), and peak 6 (chenodeoxycholic acid) are more significant than the other peaks with the standard parameter estimate 0.453, -0.166, 0.749, 0.025, respectively. So, compounds cholic acid, taurocholate sodium, and chenodeoxycholic acid might be the major anti-bacterial components in artificial C. bovis. Altogether, this work provides a general model of the combination of UPLC chromatography and anti bacterial effect to study the spectrum-effect relationships of artificial C. bovis extracts, which can be used to discover the main anti-bacterial components in artificial C. bovis or other Chinese herbal medicines with anti-bacterial effects. PMID- 22058088 TI - Bicuspid aortic valve with vertical opening and double raphe. PMID- 22058089 TI - Validation of a multi-marker model for the prediction of incident type 2 diabetes mellitus: combined results of the Inter99 and Botnia studies. AB - PURPOSE: To assess performance of a biomarker-based score that predicts the five year risk of diabetes (Diabetes Risk Score, DRS) in an independent cohort that included 15-year follow-up. METHOD: DRS was developed on the Inter99 cohort, and validated on the Botnia cohort. Performance was benchmarked against other risk assessment tools comparing calibration, time to event analysis, and net reclassification. RESULTS: The area under the receiver-operating characteristic curve (AUC) was 0.84 for the Inter99 cohort and 0.78 for the Botnia cohort. In the Botnia cohort, DRS provided better discrimination than fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance, oral glucose tolerance test or risk scores derived from Framingham or San Antonio Study cohorts. Overall reclassification with DRS was significantly better than using FPG and glucose tolerance status (p < 0.0001). In time to event analysis, rates of conversion to diabetes in low, moderate, and high DRS groups were significantly different (p < 0.001). CONCLUSION: This study validates DRS performance in an independent population, and provides a more accurate assessment of T2DM risk than other methods. PMID- 22058090 TI - Civilian firearm injury and death in England and Wales. AB - INTRODUCTION: There is currently concern in the UK that injuries and deaths caused by firearms are increasing. This is supported by small local studies but not by wider research to inform targeted prevention programmes. METHODS: A retrospective analysis was performed of firearm injuries from the Trauma Audit and Research Network (TARN) database (1998-2007), the largest national registry of serious injuries. Data were analysed to determine temporal trends in the prevalence of firearm injuries and demographic characteristics of firearm victims. The UK Office of National Statistics provided data on all deaths by firearms as TARN does not record prehospital deaths. RESULTS: Of 91 232 cases in the TARN database, 487 (0.53%) were due to firearm injury. There were 435 men and 52 women of median age 30 years. The median New Injury Severity Score in men was 18 with a mortality of 7.4%, compared with 15.5 and 3.8% for women. The highest rate of firearm injuries as a proportion of all injuries was submitted from London (1.4%), with the South East (0.23%) submitting the lowest rate. 90.5% resided in urban areas, 78% presented outside 'normal' hours and 90% were alleged assaults. As a proportion of all injuries submitted, a small upward trend in the prevalence of deaths due to firearms was demonstrated over the study period. An increase in homicides since 2000 was also noted with an increasingly younger population being involved. In contrast, data from the Office of National Statistics showed that the greatest number of deaths were self-inflicted rather than homicides (984 vs 527), with Wales having the highest number of such deaths and predominantly involving older men. CONCLUSIONS: Deaths and serious injuries caused by firearms remain rare in the civilian population of England and Wales, although an upward trend can be described. Victims of assault and homicide are predominantly young men living in urban areas and the population involved is getting younger. However, of all deaths, self-inflicted wounds are nearly twice as common as assaults, affecting predominantly older men living in more rural areas. PMID- 22058091 TI - Mycobacterium bovis bacilli Calmette-Guerin regulates leukocyte recruitment by modulating alveolar inflammatory responses. AB - Leukocyte migration into the epithelial compartment is an important feature in the active phase of mycobacterial infections. In this study, we used the Transwell model to investigate the mechanisms behind mycobacteria-induced leukocyte recruitment and investigated the role of TLR2 and TLR4 in this process. Infection of epithelial cells resulted in significantly increased secretion of the neutrophil chemotactic CXCL8 and IL-6, but no secretion of monocyte chemotactic CCL2 or TNF-alpha was observed. In contrast to epithelial response, mycobacteria-infected neutrophils and monocytes secreted all these cytokines. Corresponding with epithelial cytokine response, mycobacterial infection of the epithelial cells increased neutrophil diapedesis, but decreased monocyte recruitment. However, monocyte recruitment towards mycobacteria infected epithelial cells significantly increased following addition of neutrophil pre conditioned medium. Mycobacterial infection also increases alveolar epithelial expression of TLR2, but not TLR4, as analyzed by flow cytometry, Western blotting and visualized by confocal microscopy. Blocking of TLR2 inhibited neutrophil recruitment and cytokine secretion, while blocking of TLR4 had a lesser effect. To summarize, we found that primary alveolar epithelial cells produced a selective TLR2-dependent cytokine secretion upon mycobacterial infection. Furthermore, we found that cooperation between cells of the innate immunity is required in mounting proper antimicrobial defence. PMID- 22058092 TI - Deferiprone approved for iron overload. PMID- 22058093 TI - Drug shortage solutions elude stakeholders. PMID- 22058094 TI - Bacteremia outbreak tied to improper filtration by compounding pharmacy. PMID- 22058096 TI - Role of the pharmacist in perinatal management of HIV disease. PMID- 22058097 TI - Managing underperformers. PMID- 22058098 TI - Too many, already. PMID- 22058099 TI - New treatment options for acute edema attacks caused by hereditary angioedema. AB - PURPOSE: New treatment options for acute edema attacks caused by hereditary angioedema (HAE) are reviewed. SUMMARY: HAE is characterized by mutations in the C1 inhibitor gene leading to either a reduced expression of C1 inhibitor in the plasma or expression of a functionally impaired C1 inhibitor. HAE is classified into two major types based on the cause of the C1 inhibitor deficiency. Type I HAE is defined by a reduced expression of C1 inhibitor in the plasma, whereas type II HAE is characterized by the expression of a dysfunctional C1 inhibitor protein. Clinical data were reviewed for C1 inhibitor, ecallantide, and icatibant in the treatment of acute edema attacks caused by HAE. C1 inhibitor leads to a faster onset of edema relief and is effective in decreasing the duration of edema. Dosing strategies include fixed dosing and weight-based dosing. Optimal dosing strategies have not been established, but fixed dosing (500-1000 units) or 20 units/kg has been effective in clinical trials and reports. No comparative trials suggest that one strategy is superior to another; however, the approved labeling for acute treatment is based on weight. Ecallantide is also efficacious for treating acute episodes; however, the available evidence is limited to a single published trial. Icatibant has shown variable effects in two trials with placebo and active controls. CONCLUSION: In patients with HAE, most edema episodes only involve the skin and gastrointestinal tract, though airway obstruction caused by laryngeal angioedema is the most common cause of death. I.V. C1 inhibitor should be considered first-line treatment for acute edema attacks because of its fast onset of action and effectiveness, though it is not clear whether fixed or weight-based dosing is preferred. Ecallantide can be considered as a second-line treatment option. PMID- 22058100 TI - Risk of cancer associated with the use of angiotensin II-receptor blockers. AB - PURPOSE: The proposed mechanism by which angiotensin II and angiotensin II receptor blockers (ARBs) may influence the risk of cancer and the literature describing a possible causal relationship between ARB use and specific types of cancers are reviewed. SUMMARY: A number of cell-signaling pathways have been identified to establish a relationship between angiotensin II and cancer. Preclinical data support agonism of the angiotensin type-1 receptor by angiotensin II and unopposed stimulation of the angiotensin type-2 receptor as possible causes of proliferative and angiogenic processes. Results from a large meta-analysis suggested that ARB use is associated with a modest increase in risk of new cancer incidence. The publication of that meta-analysis led to subsequent large population analyses. A comprehensive literature review was conducted to identify studies evaluating the relationships among angiotensin II, ARBs, cancer, and malignancy. Preclinical studies evaluating the effects of angiotensin II and ARBs on proliferation and angiogenesis were selected to review how the renin angiotensin system is involved in cellular proliferation and growth. Human studies evaluating the role of ARBs in specific types of cancer were also analyzed. The literature review found limited patient-specific data in humans to support the association. The Food and Drug Administration has concluded that there is no evidence of an increased risk of cancer with ARBs. CONCLUSION: At this time there is insufficient evidence to conclude that ARBs increase the risk of cancer. Blockade of the angiotensin system through both AT(1) and AT(2) receptors may have a protective effect against malignancy. PMID- 22058101 TI - Effect of food on the single-dose pharmacokinetics and tolerability of dalfampridine extended-release tablets in healthy volunteers. AB - PURPOSE: The pharmacokinetics, bioavailability, and tolerability of dalfampridine extended-release tablets in healthy adults under fed and fasted conditions were evaluated. METHODS: The study participants (n = 30) were randomly assigned to receive one 10-mg dalfampridine tablet in a fasted condition (no food for 10-12 hours) or a fed condition (after a high-fat meal); after a seven-day washout period, participants received the same dalfampridine dosage under the converse condition. The endpoints were the maximum plasma drug concentration (C(max)) and areas under the plasma-concentration curve (AUC) for 24-hour exposure (AUC(0-24)) and total exposure (AUC(0-infinity)). A 90% two-sided confidence interval (CI) within predefined limits for the fed:fasted ratio of the geometric mean values was used as the standard for determining the absence of a significant food effect. RESULTS: Among the participants who received both treatments (n = 28), food intake was associated with a 23% increase in the log-transformed geometric mean C(max) of dalfampridine (p <= 0.10) but no significant change in mean AUC values. Eight (26.7%) of the study participants reported a total of 13 adverse events (AEs), of which only dizziness and upper abdominal pain occurred in more than one participant; all AEs were of mild-to-moderate severity. CONCLUSION: When a single 10-mg dose of dalfampridine was given to healthy volunteers after a high fat meal, a significant increase in C(max) was observed. However, overall differences in dalfampridine pharmacokinetics when the drug was administered to participants under fasting and fed conditions did not exceed predefined limits, indicating that the extended-release formulation may be taken without regard to meals. PMID- 22058102 TI - Compatibility of ceftaroline fosamil for injection with selected drugs during simulated Y-site administration. AB - PURPOSE: The physical compatibility of ceftaroline fosamil with commonly used medications and diluents (a total of 73 drugs in 219 admixtures) during simulated Y-site administration was evaluated. METHODS: Duplicate 5-mL samples of ceftaroline fosamil (2.22 mg/mL) in 5% dextrose injection, 0.9% sodium chloride injection, and lactated Ringer's injection were combined at a 1:1 ratio with samples of 73 drugs (diluted or undiluted). Visual examinations were performed with the unaided eye in fluorescent light and with the aid of a Tyndall beam; the turbidity and particulate content of each sample were also measured. The compatibility of ceftaroline fosamil with propofol was evaluated by visually inspecting for emulsion separation and particle formation after centrifugation. All evaluations were performed within 15 minutes of sample preparation and at one and four hours after preparation. RESULTS: Ceftaroline fosamil was physically compatible with 64 drugs in a combination of 196 admixtures for at least four hours, exhibiting color, clarity, turbidity, and microparticle content similar to those of control solutions. Signs of physical incompatibility, including visible precipitation, increased turbidity, and microparticle formation, were observed with 9 drugs in 23 admixtures during the four-hour observation period. CONCLUSION: Of the 73 drugs evaluated, 64 were compatible and 7 were incompatible with ceftaroline fosamil 2.22 mg/mL in 3 standard infusion solutions. Nine drugs in 23 admixtures were observed to exhibit signs of incompatibility with ceftaroline fosamil within four hours of mixing; those drugs should not be simultaneously administered via a Y-site with ceftaroline preparations. PMID- 22058103 TI - Improving patient care through implementation of an antimicrobial stewardship program. AB - PURPOSE: The implementation of an antimicrobial stewardship program at a health system is described. SUMMARY: In 2008, the Center for Antimicrobial Stewardship and Epidemiology (CASE) was formed at St. Luke's Episcopal Hospital (SLEH) to improve the quality of care for patients as it related to antimicrobial therapy. The charter of CASE contained specific aims for improving patient care, furthering clinical research, and training the next generation of clinical infectious diseases pharmacists. The CASE team consists of at least two infectious diseases pharmacists and one physician (the medical director) who provide direct oversight for antimicrobial utilization within the hospital. The CASE medical director, an infectious diseases physician, is responsible for overseeing the activities of the center. With the oversight of the CASE advisory board, the medical director develops and implements the antimicrobial stewardship and management policies for SLEH. Another key innovative feature of CASE is its extensive involvement in training new infectious diseases pharmacists and conducting research. CASE uses a model in which a clinical scenario or problem is identified, a research project is undertaken to further elucidate the problem, and policy changes are made to improve patient outcomes. The CASE team is supported by a CASE advisory board, a CASE research collaborative including university faculty, and a dedicated training program for pharmacy fellows, residents, and students. CONCLUSION: Implementation of an antimicrobial stewardship program at a health system helped decrease the inappropriate use of antibiotics, improve patient care and outcomes, further clinical research, and increase training opportunities for future clinical infectious diseases pharmacists. PMID- 22058104 TI - Standardizing i.v. infusion concentrations: National survey results. AB - PURPOSE: The results of a 2008 survey by the U.S. Pharmacopeia (USP) Safe Medication Use Expert Committee assessing the use of standardized i.v. drug concentrations at U.S. health care institutions are presented. METHODS: To evaluate progress toward the goal of standardizing and limiting the number of i.v. infusion concentrations of high-risk medications, particularly those commonly used in pediatric patients, a USP-appointed expert committee surveyed a nationally representative sample of hospital and health-system pharmacy directors; 229 usable survey responses and 174 requested lists of routinely used or "standard" concentrations (i.e., those designed to meet the needs of at least 90% of the target adult, pediatric, and neonatal populations) were received. RESULTS: The survey responses indicated that multiple concentrations of high-risk drugs are still commonly used; in some instances, as many as four standard concentrations of a single medication were reported to be in use for a particular age group. Depending on the drug and target group, the proportion of respondents reporting the use of one standard concentration for a given drug ranged from 15% to 79%. The survey data informed and helped focus the USP expert committee's efforts to develop recommended standard concentrations for 10 high-alert drugs. Also presented in this article are general principles drafted by the USP committee to guide the development of local and national standard concentrations. CONCLUSION: The results of a national USP survey indicate that many institutions do not use standard i.v. infusion concentrations of commonly used high-risk medications in adult, pediatric, or neonatal patient populations. PMID- 22058105 TI - Improving adherence to best-practice guidelines for venous thromboembolism risk assessment and prevention. AB - PURPOSE: The effectiveness of a program to improve adherence to best-practice guidelines for venous thromboembolism (VTE) risk assessment and prevention in a community hospital setting was evaluated. SUMMARY: Variation in the use of best practice guidelines for VTE risk assessment and prevention with regard to the frequency of VTE risk assessment and the risk score assigned, as well as the communication of the risk of VTE and the need for prophylaxis to treating physicians, was found. To improve adherence to established guidelines, the responsibilities of a nurse case manager were expanded to serve as a single point of contact who was accountable for identifying high-risk patients and advocating for appropriate pharmacologic prophylaxis in the absence of contraindications. To facilitate the role of the nurse case manager, an automated VTE-risk-assessment tool was developed to reliably identify high-risk patients in real time. This intervention was evaluated from January 1 to June 30, 2010. Before the intervention, contraindications to anticoagulation were reported for 19.1% of high-risk patients not receiving prophylaxis and pharmacologic prophylaxis was ordered for 47.9% of high-risk patients without contraindications. During the course of the intervention, contraindications to anticoagulation were reported for 36.2% of high-risk patients not receiving prophylaxis and pharmacologic prophylaxis was ordered for 64.9% of high-risk patients without contraindications. CONCLUSION: The appointment of a nurse case manager trained in anticoagulation and the development of an automated VTE-risk-assessment tool to identify patients at high risk of VTE were associated with improved adherence to best-practice guidelines for VTE risk assessment and prevention. PMID- 22058106 TI - Evaluating the mind's eye: the metacognition of visual imagery. AB - Can people evaluate phenomenal qualities of internally generated experiences, such as whether a mental image is vivid or detailed? This question exemplifies a problem of metacognition: How well do people know their own thoughts? In the study reported here, participants were instructed to imagine a specific visual pattern and rate its vividness, after which they were presented with an ambiguous rivalry display that consisted of the previously imagined pattern plus an orthogonal pattern. On individual trials, higher ratings of vividness predicted a greater likelihood that the imagined pattern would appear dominant when the participant was subsequently presented with the binocular rivalry display. Off line self-report questionnaires measuring imagery vividness also predicted individual differences in the strength of imagery bias over the entire study. Perceptual bias due to mental imagery could not be attributed to demand characteristics, as no bias was observed on catch-trial presentations of mock rivalry displays. Our findings provide novel evidence that people have a good metacognitive understanding of their own mental imagery and can reliably evaluate the vividness of single episodes of imagination. PMID- 22058107 TI - Immunizing against prejudice: effects of disease protection on attitudes toward out-groups. AB - Contemporary interpersonal biases are partially derived from psychological mechanisms that evolved to protect people against the threat of contagious disease. This behavioral immune system effectively promotes disease avoidance but also results in an overgeneralized prejudice toward people who are not legitimate carriers of disease. In three studies, we tested whether experiences with two modern forms of disease protection (vaccination and hand washing) attenuate the relationship between concerns about disease and prejudice against out-groups. Study 1 demonstrated that when threatened with disease, vaccinated participants exhibited less prejudice toward immigrants than unvaccinated participants did. In Study 2, we found that framing vaccination messages in terms of immunity eliminated the relationship between chronic germ aversion and prejudice. In Study 3, we directly manipulated participants' protection from disease by having some participants wash their hands and found that this intervention significantly influenced participants' perceptions of out-group members. Our research suggests that public-health interventions can benefit society in areas beyond immediate health-related domains by informing novel, modern remedies for prejudice. PMID- 22058108 TI - Status, race, and money: the impact of racial hierarchy on willingness to pay. AB - A deeply entrenched status hierarchy in the United States classifies African Americans as lower status than Caucasians. Concurrently, African Americans face marketplace discrimination; they are treated as inferior and poor. Because having money and spending money signify status, we explored whether African Americans might elevate their willingness to pay for products in order to fulfill status needs. In Studies 1 and 2, explicit activation of the race concept led some African Americans to pay more than they would otherwise pay and also more than Caucasians. Individual differences in perceived status disadvantage and racial identification moderated this result. In Study 3, when race was salient, an overt status threat (inferior treatment in a purchasing context) similarly led African Americans, but not Caucasians, to pay more than they would otherwise pay. This research illustrates how African Americans whose status is threatened use spending as a way to assert status. PMID- 22058109 TI - Sick body, vigilant mind: the biological immune system activates the behavioral immune system. AB - Activation of the behavioral immune system has been shown to promote activation of the biological immune system. The current research tested the hypothesis that activation of the biological immune system (as a result of recent illness) promotes activation of the behavioral immune system. Participants who had recently been ill, and had therefore recently experienced activation of their biological immune system, displayed heightened attention to (Study 1) and avoidance of (Study 2) disfigured individuals--cognitive and behavioral processes reflecting activation of the behavioral immune system. These findings shed light on the interactive nature of biological and psychological mechanisms designed to help people overcome the threat of disease. PMID- 22058110 TI - Effect of monomer composition of polymer matrix on flexural properties of glass fibre-reinforced orthodontic archwire. AB - To compare force levels obtained from glass fibre-reinforced composite (FRC) archwires. Specifically, FRC wires were compared with polymer matrices having different dimethacrylate monomer compositions. FRC material (E-glass provided by Stick Tech Ltd, Turku, Finland) with continuous unidirectional glass fibres and four different types of dimethacrylate monomer compositions for the resin matrix were tested. Cross-sectionally round FRC archwires fitting into the 0.3 mm slot of a bracket were divided into 16 groups with six specimens in each group. Glass fibres were impregnated by the manufacturer, and they were initially light-cured by hand light-curing unit or additionally post-cured in light-curing oven. The FRC archwire specimens were tested at 37 degrees C according to a three-point bending test in dry and wet conditions using a span length of 10 mm and a crosshead speed of 1.0 mm/minute. The wires were loaded until final failure. The data were statistically analysed using analysis of variance (ANOVA). The dry FRC archwire specimens revealed higher load values than water stored ones, regardless of the polymer matrix. A majority of the FRC archwires showed higher load values after being post-cured. ANOVA revealed that the polymer matrix, curing method, and water storage had a significant effect (P < 0.05) on the flexural behaviour of the FRC archwire. Polymer matrix composition, curing method, and water storage affected the flexural properties and thus, force level and working range which could be obtained from the FRC archwire. PMID- 22058111 TI - Automated analysis and classification of infected macrophages using bright-field amplitude contrast data. AB - This article presents a methodology for acquisition and analysis of bright-field amplitude contrast image data in high-throughput screening (HTS) for the measurement of cell density, cell viability, and classification of individual cells into phenotypic classes. We present a robust image analysis pipeline, where the original data are subjected to image standardization, image enhancement, and segmentation by region growing. This work develops new imaging and analysis techniques for cell analysis in HTS and successfully addresses a particular need for direct measurement of cell density and other features without using dyes. PMID- 22058112 TI - A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion in familial atypical hemolytic uremic syndrome. AB - Genomic disorders affecting the genes encoding factor H (fH) and the 5 factor H related proteins have been described in association with atypical hemolytic uremic syndrome. These include deletions of CFHR3, CFHR1, and CFHR4 in association with fH autoantibodies and the formation of a hybrid CFH/CFHR1 gene. These occur through nonallelic homologous recombination secondary to the presence of large segmental duplications (macrohomology) in this region. Using multiplex ligation-dependent probe amplification to screen for such genomic disorders, we have identified a large atypical hemolytic uremic syndrome family where a deletion has occurred through microhomology-mediated end joining rather than nonallelic homologous recombination. In the 3 affected persons of this family, we have shown that the deletion results in formation of a CFH/CFHR3 gene. We have shown that the protein product of this is a 24 SCR protein that is secreted with normal fluid-phase activity but marked loss of complement regulation at cell surfaces despite increased heparin binding. In this study, we have therefore shown that microhomology in this area of chromosome 1 predisposes to disease associated genomic disorders and that the complement regulatory function of fH at the cell surface is critically dependent on the structural integrity of the whole molecule. PMID- 22058113 TI - Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts. AB - Diamond-Blackfan anemia (DBA) is associated with developmental defects and profound anemia. Mutations in genes encoding a ribosomal protein of the small (e.g., RPS19) or large (e.g., RPL11) ribosomal subunit are found in more than half of these patients. The mutations cause ribosomal haploinsufficiency, which reduces overall translation efficiency of cellular mRNAs. We reduced the expression of Rps19 or Rpl11 in mouse erythroblasts and investigated mRNA polyribosome association, which revealed deregulated translation initiation of specific transcripts. Among these were Bag1, encoding a Hsp70 cochaperone, and Csde1, encoding an RNA-binding protein, and both were expressed at increased levels in erythroblasts. Their translation initiation is cap independent and starts from an internal ribosomal entry site, which appeared sensitive to knockdown of Rps19 or Rpl11. Mouse embryos lacking Bag1 die at embryonic day 13.5, with reduced erythroid colony forming cells in the fetal liver, and low Bag1 expression impairs erythroid differentiation in vitro. Reduced expression of Csde1 impairs the proliferation and differentiation of erythroid blasts. Protein but not mRNA expression of BAG1 and CSDE1 was reduced in erythroblasts cultured from DBA patients. Our data suggest that impaired internal ribosomal entry site mediated translation of mRNAs expressed at increased levels in erythroblasts contributes to the erythroid phenotype of DBA. PMID- 22058114 TI - Rituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment. AB - Cancer patients are often encouraged to receive seasonal influenza vaccination. The monoclonal antibody rituximab is widely used in treatment of non-Hodgkin lymphoma. This results in a prolonged depletion of normal B cells, which might impair humoral responses. The aim of the present study was to investigate whether lymphoma patients undergoing rituximab-containing treatment regimens or having received such regimens within the past 6 months were able to mount protective antibody responses to the influenza A(H1N1) 2009 virus vaccine Pandemrix during the 2009 "swine flu" pandemic. Contrary to the control group, where 82% responded adequately to the vaccine, none of the 67 patients achieved protective antibody titers, suggesting that lymphoma patients receiving rituximab-containing regimens might not benefit from this vaccine. It is important that doctors who care for such patients are aware that they may fail to respond not only to the influenza vaccine, but also to other common vaccines. PMID- 22058115 TI - Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program. AB - The Tax oncoprotein encoded by the human T-cell leukemia virus type 1 plays a pivotal role in viral persistence and pathogenesis. Human T-cell leukemia virus type 1-infected cells proliferate faster than normal lymphocytes, expand through mitotic division, and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax modulates the spatiotemporal program of origin activation and fires supplementary origins at the onset of S phase. Thereby, Tax increases the DNA replication rate, accelerates S phase progression, but also generates a replicative stress characterized by the presence of genomic lesions. Mechanistically, Tax favors p300 recruitment and histone hyperacetylation at late replication domains, advancing their replication timing in early S phase. PMID- 22058116 TI - Protumoral role of monocytes in human B-cell precursor acute lymphoblastic leukemia: involvement of the chemokine CXCL10. AB - Myelomonocytic cells play a key role in the progression of many solid tumors. However, very little is known about their contribution to the progression of hematopoietic cancers. We investigated the role of monocytes in the progression of human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). We demonstrated that coculturing human monocytes in vitro with CD19+ BCP-ALL blasts from patients "conditioned" them to an inflammatory phenotype characterized by significant up regulation of the chemokine, CXCL10. This phenotype was also observable ex vivo in monocytes isolated from BCP-ALL patients, which show elevated CXCL10 production compared with monocytes from healthy donors. Functionally, the "conditioned" monocytes promoted migration and invasive capacity of BCP-ALL cells. Increased invasion was mediated by matrix metalloproteinase 9 expression and activity in the BCP-ALL cells induced by the monocyte-derived CXCL10. However, neither the "conditioned" monocytes nor the CXCL10 produced by these cells had any effect on the proliferation/viability of BCP-ALL cells and angiogenesis. Collectively, our results strongly suggest a protumoral role for human monocytes in BCP-ALL, orchestrated by CXCL10 and its effect on tumor cell migration and invasion. These observations highlight the importance of the CXCL10/CXCR3 chemokine circuit in BCP-ALL progression. PMID- 22058117 TI - Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML. AB - Deletions of chromosome 5q are associated with poor outcomes in acute myeloid leukemia (AML) suggesting the presence of tumor suppressor(s) at the locus. However, definitive identification of putative tumor suppressor genes remains controversial. Here we show that a 106-nucleotide noncoding RNA vault RNA2-1 (vtRNA2-1), previously misannotated as miR886, could potentially play a role in the biology and prognosis of AML. vtRNA2-1 is transcribed by polymerase III and is monoallelically methylated in 75% of healthy individuals whereas the remaining 25% of the population have biallelic hypomethylation. AML patients without methylation of VTRNA2-1 have a considerably better outcome than those with monoallelic or biallelic methylation (n = 101, P = .001). We show that methylation is inversely correlated with vtRNA2-1 expression, and that 5 azanucleosides induce vtRNA2-1 and down-regulate the phosphorylated RNA-dependent protein kinase (pPKR), whose activity has been shown to be modulated by vtRNA2-1. Because pPKR promotes cell survival in AML, the data are consistent with vtRNA2-1 being a tumor suppressor in AML. This is the first study to show that vtRNA2-1 might play a significant role in AML, that it is either mono- or biallelically expressed in the blood cells of healthy individuals, and that its methylation state predicts outcome in AML. PMID- 22058118 TI - Carbodiimide cross-linking inactivates soluble and matrix-bound MMPs, in vitro. AB - Matrix metalloproteinases (MMPs) cause collagen degradation in hybrid layers created by dentin adhesives. This in vitro study evaluated the feasibility of using a cross-linking agent, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), to inactivate soluble rhMMP-9, as an example of dentin MMPs, and matrix bound dentin proteases. The inhibitory effects of 5 EDC concentrations (0.01-0.3 M) and 5 incubation times (1-30 min) on soluble rhMMP-9 were screened with an MMP assay kit. The same EDC concentrations were used to evaluate their inhibitory effects on endogenous proteinases from completely demineralized dentin beams that were incubated in simulated body fluid for 30 days. Decreases in modulus of elasticity (E) and dry mass of the beams, and increases in hydroxyproline content of hydrolysates derived from the incubation medium were used as indirect measures of matrix collagen hydrolysis. All EDC concentrations and pre-treatment times inactivated MMP-9 by 98% to 100% (p < 0.05) compared with non-cross-linked controls. Dentin beams incubated in 0.3 M EDC showed only a 9% decrease in E (45% decrease in control), a 3.6% to 5% loss of dry mass (18% loss in control), and significantly less solubilized hydroxyproline when compared with the control without EDC cross-linking (p < 0.05). It is concluded that EDC application for 1 min may be a clinically relevant and effective means for inactivating soluble rhMMP-9 and matrix-bound dentin proteinases if further studies demonstrate that EDC is not toxic to pulpal tissues. PMID- 22058119 TI - Rapid estrogenic effects on TMJ-responsive brainstem neurons. AB - Estrogen status is a risk factor for temporomandibular muscle and joint disorders (TMJD) and other craniofacial pain conditions. The basis for estrogen modulation of pain is poorly understood and has often been attributed to long-term genomic effects. However, estrogens also act rapidly through membrane-initiated mechanisms to alter neural activity. To assess if estrogens act rapidly to affect TMJ-responsive neurons, we applied 17beta-estradiol (E2) directly at the spinomedullary (Vc/C(1-2)) region, the initial brainstem site for synaptic integration of TMJ sensory signals, while recording single neuron activity. In ovariectomized female rats, E2 rapidly (within 10 minutes) and reversibly reduced TMJ-evoked neural activity at the Vc/C(1-2) region. The effect was estrogen receptor (ER) subtype-specific, since ERbeta agonists inhibited, while an ERbeta agonist enhanced, evoked activity. A membrane-mediated mechanism was indicated, since the membrane-impermeable analogue, E(2)-BSA, mimicked the inhibitory effect of E2 and was prevented by an ER antagonist. This study demonstrated that E2 acted rapidly, through membrane-mediated pathways, and locally at the Vc/C(1-2) region, to modulate sensory signals from the TMJ region. These results were consistent with the hypothesis that estrogens can act rapidly at the level of the trigeminal brainstem complex to influence sensory integration of TMJ-related information. PMID- 22058120 TI - Determinants of exclusive breastfeeding in a cohort of primiparous periurban peruvian mothers. AB - The authors aimed to identify factors associated with exclusive breastfeeding (EBF) among 117 Peruvian mothers planning to breastfeed exclusively. Data were collected on days 0 and 3, and months 1, 3, and 6. Exclusive breastfeeding status was evaluated with a 24-hour recall of infant diet. Exclusive breastfeeding rates were 74%, 72%, and 35% at 1, 3, and 6 months, respectively. At 3 months, lower maternal education, greater breastfeeding frequency (day 3), greater breast pain (day 3), and depot medroxyprogesterone acetate use (3 months) were associated with EBF, after adjusting for EBF intentions. At 6 months, greater infant birth weight and mother-not employed were associated with EBF, after controlling for EBF intentions. More educated and working mothers, and infants with lower birth weight should be targeted in interventions to promote EBF in urban Peru. Research is also warranted to explore the factors linking depot medroxyprogesterone acetate use and breast pain with EBF duration. PMID- 22058121 TI - Molecularly imprinted solid-phase extraction for the selective HPLC determination of ractopamine in pig urine. AB - A method was developed for the determination of ractopamine in pig urine using molecularly imprinted solid-phase extraction (MISPE) as the sample clean-up technique combined with high-performance liquid chromatography. The molecularly imprinted polymer (MIP) was synthesized in acetonitrile-triethylamine system using ractopamine (RAC) as the template and acrylamide as the monomer. The binding capacity of the polymer toward RAC was found to be about 2.57 mg of ractopamine/g of polymer. The optimal procedures for MISPE consisted of conditioning with 3 mL methanol, equilibrating with 3 mL of water, loading volume of <10 mL of aqueous sample (pH 7), washing with 3 mL water and 3 mL methanol, and eluting with 5 mL of 5% ammonia in methanol. In the four spiked samples with the levels of 0.01, 0.1, 1.0 and 5.0 MUg/mL, the mean recoveries of analyte on the MIP were higher than 90% with relative standard deviation <10%, and significant differences between imprinted and non-imprinted materials were observed. The MIP selectivity was evaluated by checking 11 drugs with similar and different molecular structures to that of RAC. The characteristics of three dimensional cavities and hydrogen bond interaction were regarded as the main factors that dominated the retention of RAC on the MISPE cartridge. PMID- 22058122 TI - Quality of care in independent sector treatment centres. PMID- 22058123 TI - Number of children admitted to hospital with viral disease rose markedly last year. PMID- 22058124 TI - House of Lords' vote on health secretary's responsibility for NHS services is delayed. PMID- 22058125 TI - Treatment of man with mental illness at UK detention centre breached human rights. PMID- 22058126 TI - Strong epigenetic similarity between maize centromeric and pericentromeric regions at the level of small RNAs, DNA methylation and H3 chromatin modifications. AB - Both kinetochore function and sister chromatid cohesion can depend upon pericentromere chromatin structure, and factors associated with heterochromatin have been proposed to have general, conserved roles in distinguishing centromeres and pericentromeres and in conferring pericentromere-intrinsic functions. We applied genome-wide sequencing approaches to quantify RNA expression, DNA methylation and histone modification distributions in maize (Zea mays), focusing on two maize chromosomes with nearly fully sequenced centromeres and pericentromeres. Aside from the presence of the Histone H3 variant common to all centromeres, Centromeric Histone H3 (CENH3), we found no RNA expression or chromatin modifications that clearly differentiate pericentromeres from either centromeres or from chromosome arms, nor did we identify an epigenetic signature that accurately predicts CENH3 location. RNA expression and chromatin modification frequencies were broadly associated with distance from centromeres, gradually peaking or dipping toward arms. When interpreted in the context of experimental data from other systems, our results suggest that centromeres may confer essential functions (such as cohesion retention) to flanking sequence regardless of the local heterochromatin profile. PMID- 22058127 TI - MACiE: exploring the diversity of biochemical reactions. AB - MACiE (which stands for Mechanism, Annotation and Classification in Enzymes) is a database of enzyme reaction mechanisms, and can be accessed from http://www.ebi.ac.uk/thornton-srv/databases/MACiE/. This article presents the release of Version 3 of MACiE, which not only extends the dataset to 335 entries, covering 182 of the EC sub-subclasses with a crystal structure available (~90%), but also incorporates greater chemical and structural detail. This version of MACiE represents a shift in emphasis for new entries, from non-homologous representatives covering EC reaction space to enzymes with mechanisms of interest to our users and collaborators with a view to exploring the chemical diversity of life. We present new tools for exploring the data in MACiE and comparing entries as well as new analyses of the data and new searches, many of which can now be accessed via dedicated Perl scripts. PMID- 22058128 TI - Characterization of the kinetic and thermodynamic landscape of RNA folding using a novel application of isothermal titration calorimetry. AB - A novel isothermal titration calorimetry (ITC) method was applied to investigate RNA helical packing driven by the GAAA tetraloop-receptor interaction in magnesium and potassium solutions. Both the kinetics and thermodynamics were obtained in individual ITC experiments, and analysis of the kinetic data over a range of temperatures provided Arrhenius activation energies (DeltaH(?)) and Eyring transition state entropies (DeltaS(?)). The resulting rich dataset reveals strongly contrasting kinetic and thermodynamic profiles for this RNA folding system when stabilized by potassium versus magnesium. In potassium, association is highly exothermic (DeltaH(25 degrees C) = -41.6 +/- 1.2 kcal/mol in 150 mM KCl) and the transition state is enthalpically barrierless (DeltaH(?) = -0.6 +/- 0.5). These parameters are significantly positively shifted in magnesium (DeltaH(25 degrees C) = -20.5 +/- 2.1 kcal/mol, DeltaH(?) = 7.3 +/- 2.2 kcal/mol in 0.5 mM MgCl(2)). Mixed salt solutions approximating physiological conditions exhibit an intermediate thermodynamic character. The cation-dependent thermodynamic landscape may reflect either a salt-dependent unbound receptor conformation, or alternatively and more generally, it may reflect a small per cation enthalpic penalty associated with folding-coupled magnesium uptake. PMID- 22058129 TI - DistiLD Database: diseases and traits in linkage disequilibrium blocks. AB - Genome-wide association studies (GWAS) have identified thousands of single nucleotide polymorphisms (SNPs) associated with the risk of hundreds of diseases. However, there is currently no database that enables non-specialists to answer the following simple questions: which SNPs associated with diseases are in linkage disequilibrium (LD) with a gene of interest? Which chromosomal regions have been associated with a given disease, and which are the potentially causal genes in each region? To answer these questions, we use data from the HapMap Project to partition each chromosome into so-called LD blocks, so that SNPs in LD with each other are preferentially in the same block, whereas SNPs not in LD are in different blocks. By projecting SNPs and genes onto LD blocks, the DistiLD database aims to increase usage of existing GWAS results by making it easy to query and visualize disease-associated SNPs and genes in their chromosomal context. The database is available at http://distild.jensenlab.org/. PMID- 22058130 TI - pre-miRNA profiles obtained through application of locked nucleic acids and deep sequencing reveals complex 5'/3' arm variation including concomitant cleavage and polyuridylation patterns. AB - Recent research hints at an underappreciated complexity in pre-miRNA processing and regulation. Global profiling of pre-miRNA and its potential to increase understanding of the pre-miRNA landscape is impeded by overlap with highly expressed classes of other non coding (nc) RNA. Here, we present a data set excluding these RNA before sequencing through locked nucleic acids (LNA), greatly increasing pre-miRNA sequence counts with no discernable effect on pre-miRNA or mature miRNA sequencing. Analysis of profiles generated in total, nuclear and cytoplasmic cell fractions reveals that pre-miRNAs are subject to a wide range of regulatory processes involving loci-specific 3'- and 5'-end variation entailing complex cleavage patterns with co-occurring polyuridylation. Additionally, examination of nuclear-enriched flanking sequences of pre-miRNA, particularly those derived from polycistronic miRNA transcripts, provides insight into miRNA and miRNA-offset (moRNA) production, specifically identifying novel classes of RNA potentially functioning as moRNA precursors. Our findings point to particularly intricate regulation of the let-7 family in many ways reminiscent of DICER1-independent, pre-mir-451-like processing, introduce novel and unify known forms of pre-miRNA regulation and processing, and shed new light on overlooked products of miRNA processing pathways. PMID- 22058131 TI - 959 Nematode Genomes: a semantic wiki for coordinating sequencing projects. AB - Genome sequencing has been democratized by second-generation technologies, and even small labs can sequence metazoan genomes now. In this article, we describe '959 Nematode Genomes'--a community-curated semantic wiki to coordinate the sequencing efforts of individual labs to collectively sequence 959 genomes spanning the phylum Nematoda. The main goal of the wiki is to track sequencing projects that have been proposed, are in progress, or have been completed. Wiki pages for species and strains are linked to pages for people and organizations, using machine- and human-readable metadata that users can query to see the status of their favourite worm. The site is based on the same platform that runs Wikipedia, with semantic extensions that allow the underlying taxonomy and data storage models to be maintained and updated with ease compared with a conventional database-driven web site. The wiki also provides a way to track and share preliminary data if those data are not polished enough to be submitted to the official sequence repositories. In just over a year, this wiki has already fostered new international collaborations and attracted newcomers to the enthusiastic community of nematode genomicists. www.nematodegenomes.org. PMID- 22058132 TI - PlantNATsDB: a comprehensive database of plant natural antisense transcripts. AB - Natural antisense transcripts (NATs), as one type of regulatory RNAs, occur prevalently in plant genomes and play significant roles in physiological and pathological processes. Although their important biological functions have been reported widely, a comprehensive database is lacking up to now. Consequently, we constructed a plant NAT database (PlantNATsDB) involving approximately 2 million NAT pairs in 69 plant species. GO annotation and high-throughput small RNA sequencing data currently available were integrated to investigate the biological function of NATs. PlantNATsDB provides various user-friendly web interfaces to facilitate the presentation of NATs and an integrated, graphical network browser to display the complex networks formed by different NATs. Moreover, a 'Gene Set Analysis' module based on GO annotation was designed to dig out the statistical significantly overrepresented GO categories from the specific NAT network. PlantNATsDB is currently the most comprehensive resource of NATs in the plant kingdom, which can serve as a reference database to investigate the regulatory function of NATs. The PlantNATsDB is freely available at http://bis.zju.edu.cn/pnatdb/. PMID- 22058133 TI - ConoServer: updated content, knowledge, and discovery tools in the conopeptide database. AB - ConoServer (http://www.conoserver.org) is a database specializing in the sequences and structures of conopeptides, which are toxins expressed by marine cone snails. Cone snails are carnivorous gastropods, which hunt their prey using a cocktail of toxins that potently subvert nervous system function. The ability of these toxins to specifically target receptors, channels and transporters of the nervous system has attracted considerable interest for their use in physiological research and as drug leads. Since the founding publication on ConoServer in 2008, the number of entries in the database has nearly doubled, the interface has been redesigned and new annotations have been added, including a more detailed description of cone snail species, biological activity measurements and information regarding the identification of each sequence. Automatically updated statistics on classification schemes, three-dimensional structures, conopeptide-bearing species and endoplasmic reticulum signal sequence conservation trends, provide a convenient overview of current knowledge on conopeptides. Transcriptomics and proteomics have began generating massive numbers of new conopeptide sequences, and two dedicated tools have been recently implemented in ConoServer to standardize the analysis of conopeptide precursor sequences and to help in the identification by mass spectrometry of toxins whose sequences were predicted at the nucleic acid level. PMID- 22058134 TI - Effect of exercise referral schemes in primary care on physical activity and improving health outcomes: systematic review and meta-analysis. AB - OBJECTIVE: To assess the impact of exercise referral schemes on physical activity and health outcomes. Design Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, PsycINFO, Cochrane Library, ISI Web of Science, SPORTDiscus, and ongoing trial registries up to October 2009. We also checked study references. Study selection Design: randomised controlled trials or non-randomised controlled (cluster or individual) studies published in peer review journals. POPULATION: sedentary individuals with or without medical diagnosis. Exercise referral schemes defined as: clear referrals by primary care professionals to third party service providers to increase physical activity or exercise, physical activity or exercise programmes tailored to individuals, and initial assessment and monitoring throughout programmes. Comparators: usual care, no intervention, or alternative exercise referral schemes. RESULTS: Eight randomised controlled trials met the inclusion criteria, comparing exercise referral schemes with usual care (six trials), alternative physical activity intervention (two), and an exercise referral scheme plus a self determination theory intervention (one). Compared with usual care, follow-up data for exercise referral schemes showed an increased number of participants who achieved 90-150 minutes of physical activity of at least moderate intensity per week (pooled relative risk 1.16, 95% confidence intervals 1.03 to 1.30) and a reduced level of depression (pooled standardised mean difference -0.82, -1.28 to -0.35). Evidence of a between group difference in physical activity of moderate or vigorous intensity or in other health outcomes was inconsistent at follow-up. We did not find any difference in outcomes between exercise referral schemes and the other two comparator groups. None of the included trials separately reported outcomes in individuals with specific medical diagnoses. Substantial heterogeneity in the quality and nature of the exercise referral schemes across studies might have contributed to the inconsistency in outcome findings. Conclusions Considerable uncertainty remains as to the effectiveness of exercise referral schemes for increasing physical activity, fitness, or health indicators, or whether they are an efficient use of resources for sedentary people with or without a medical diagnosis. PMID- 22058135 TI - Promoting physical activity in primary care. PMID- 22058136 TI - Epidemiology of chronic kidney disease in children in Serbia. AB - BACKGROUND: The epidemiological information from well-defined populations regarding childhood chronic kidney disease (CKD), particularly those concerning non-terminal stages, are scanty. The epidemiology of CKD in children is often based on renal replacement therapy (RRT) data, which means that a considerable number of children in earlier stages of CKD are missed as they will reach end stage renal disease (ESRD) in adulthood. Here, we report the basic epidemiological data on childhood CKD in Serbia, gathered over the 10-year period of activity of the Serbian Pediatric Registry of Chronic Kidney Disease. METHODS: Since 2000-09, data on incidence, prevalence, aetiology, treatment modalities and outcome of children aged 0-18 years, with CKD Stages 2-4 and CKD Stage 5, were collected by reporting index cases from paediatric centres. RESULTS: Three hundred and thirty-six children were registered (211 boys, 125 girls, male/female ratio 1.7). The median age at registration was 9.0 years [interquartile range (IQR) 3-13]. Median follow-up was 4.0 years (IQR, 1-9). The median glomerular filtration rate (GFR) at the time of the registration was 39.6 mL/min/1.73m(2) (IQR, 13.8-65.4). Median annual incidence of CKD 2-5 stages was 14.3 per million age-related population (p.m.a.r.p.), while those of CKD 2-4 or CKD 5 were 9.1 and 5.7 p.m.a.r.p., respectively. The median prevalence of CKD 2-5 was 96.1 p.m.a.r.p., 52.8 p.m.a.r.p. in CKD 2-4 and 62.2 p.m.a.r.p. in CKD 5. The main causes of CKD were congenital anomalies of kidney and urinary tract and hereditary nephropathies. Kidney survival was the worst in children with glomerular diseases and in those with advanced CKD. Haemodialysis was the most common first modality of RRT. Mortality rate was 4.5%, mainly due to cardiovascular and infectious complications. CONCLUSIONS: Epidemiology of paediatric CKD in Serbia is similar to that reported from developed European countries. The knowledge of the epidemiology of earlier stages of CKD is essential for both institution of renoprotective therapy and planning of RRT, a fact of paramount importance in countries with limited resources. PMID- 22058137 TI - Diagnosis and management of anal intraepithelial neoplasia and anal cancer. PMID- 22058138 TI - Four in 10 cases of alleged abuse of vulnerable adults occur in own homes. PMID- 22058139 TI - Central nervous system recruitment of effector memory CD8+ T lymphocytes during neuroinflammation is dependent on alpha4 integrin. AB - Clonally expanded CD8(+) T lymphocytes are present in multiple sclerosis lesions, as well as in the cerebrospinal fluid of patients with multiple sclerosis. In experimental autoimmune encephalomyelitis, CD8(+) T lymphocytes are found in spinal cord and brainstem lesions. However, the exact phenotype of central nervous system-infiltrating CD8(+) T lymphocytes and the mechanism by which these cells cross the blood-brain barrier remain largely unknown. Using cerebrospinal fluid from patients with multiple sclerosis, spinal cord from experimental autoimmune encephalomyelitis and coronavirus-induced encephalitis, we demonstrate that central nervous system-infiltrating CD8(+) T lymphocytes are mostly of the effector memory phenotype (CD62L(-) CCR7(-) granzymeB(hi)). We further show that purified human effector memory CD8(+) T lymphocytes transmigrate more readily across blood-brain barrier-endothelial cells than non-effector memory CD8(+) T lymphocytes, and that blood-brain barrier endothelium promotes the selective recruitment of effector memory CD8(+) T lymphocytes. Furthermore, we provide evidence for the recruitment of interferon-gamma- and interleukin-17-secreting CD8(+) T lymphocytes by human and mouse blood-brain barrier endothelium. Finally, we show that in vitro migration of CD8(+) T lymphocytes across blood-brain barrier-endothelial cells is dependent on alpha4 integrin, but independent of intercellular adhesion molecule-1/leucocyte function-associated antigen-1, activated leucocyte cell adhesion molecule/CD6 and the chemokine monocyte chemotactic protein-1/CCL2. We also demonstrate that in vivo neutralization of very late antigen-4 restricts central nervous system infiltration of CD8(+) T lymphocytes in active immunization and adoptive transfer experimental autoimmune encephalomyelitis, and in coronavirus-induced encephalitis. Our study thus demonstrates an active role of the blood-brain barrier in the recruitment of effector memory CD8(+) T lymphocytes to the CNS compartment and defines alpha4 integrin as a major contributor of CD8(+) T lymphocyte entry into the brain. PMID- 22058140 TI - alpha1,3 glucans are dispensable in Aspergillus fumigatus. AB - A triple alpha1,3 glucan synthase mutant of Aspergillus fumigatus obtained by successive deletions of the three alpha1,3 glucan synthase genes (AGS1, AGS2, and AGS3) has a cell wall devoid of alpha1,3 glucans. The lack of alpha1,3 glucans affects neither conidial germination nor mycelial vegetative growth and is compensated by an increase in beta1,3 glucan and/or chitin content. PMID- 22058141 TI - A trypanosomal pentatricopeptide repeat protein stabilizes the mitochondrial mRNAs of cytochrome oxidase subunits 1 and 2. AB - The pentatricopeptide repeat (PPR) protein family consists of organellar proteins predicted to bind to specific RNA sequences. Plants have hundreds of distinct PPR proteins, whereas other eukaryotes generally have many fewer. The genome of the parasitic protozoon Trypanosoma brucei is predicted to encode more than 30 different PPR proteins, which is an extraordinarily high number for a nonplant organism. Here we report the characterization T. brucei PPR9 (TbPPR9). Epitope tagging shows that the protein is exclusively mitochondrially localized. Interestingly, while in induced RNA interference cell lines TbPPR9 is efficiently downregulated, the level of its mRNA is not affected. Ablation of TbPPR9 selectively abolishes oxidative but not mitochondrial substrate-level phosphorylation. The molecular basis of this phenotype is the fact that TbPPR9 is required for the stability of the cytochrome oxidase subunit 1 (COX1) and COX2 mRNAs. This is supported by the observation that ablation of TbPPR9 destabilizes the COX complex but not the cytochrome bc1 or the ATP synthase complex. Moreover, it was shown by blue native gel electrophoresis that TbPPR9 is present in a large complex of unknown composition. PMID- 22058142 TI - The Neurospora crassa DCC-1 protein, a putative histidine kinase, is required for normal sexual and asexual development and carotenogenesis. AB - Two-component signaling pathways based on phosphoryl group transfer between histidine kinase and response regulator proteins regulate environmental responses in bacteria, archaea, plants, slime molds, and fungi. Here we characterize a mutant form of DCC-1, a putative histidine kinase encoded by the NCU00939 gene of the filamentous fungus Neurospora crassa. We show that this protein participates in the regulation of processes such as conidiation, perithecial development, and, to a certain degree, carotenogenesis. Furthermore, DCC-1 is suggested to exert its effect by promoting cyclic AMP production, thereby placing this protein within the context of a signaling pathway. PMID- 22058143 TI - Proteomic analysis of Trichoderma atroviride reveals independent roles for transcription factors BLR-1 and BLR-2 in light and darkness. AB - The genus Trichoderma is one of the most widely used biological control agents of plant-pathogenic fungi. The main mechanism for survival and dispersal of Trichoderma is through the production of asexual spores (conidia). The transition from filamentous growth to conidiation can be triggered by light, nutrient deprivation, and mechanical damage of the mycelium. We conducted proteomic profiling analyses of Trichoderma atroviride after a blue light pulse. The use of two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) analysis allowed us to identify 72 proteins whose expression was affected by blue light. Functional category analysis showed that the various proteins are involved in metabolism, cell rescue, and protein synthesis. We determined the relationship between mRNA levels of selected genes 30 min after a light pulse and protein expression levels at different times after the pulse and found this correlation to be very weak. The correlation was highest when protein and mRNA levels were compared for the same time point. The transcription factors BLR-1 and BLR-2 are vital to the photoconidiation process; here we demonstrate that both BLR proteins are active in darkness and affect several elements at both the transcript and protein levels. Unexpectedly, in darkness, downregulation of proteins prevailed in the Deltablr-1 mutant, while upregulation of proteins predominated in the Deltablr-2 mutant. Our data demonstrate that the BLR proteins play roles individually and as a complex. PMID- 22058144 TI - Risks and benefits of thoracic epidural anaesthesia. AB - Thoracic epidural anaesthesia (TEA) reduces cardiac and splanchnic sympathetic activity and thereby influences perioperative function of vital organ systems. A recent meta-analysis suggested that TEA decreased postoperative cardiac morbidity and mortality. TEA appears to ameliorate gut injury in major surgery as long as the systemic haemodynamic effects of TEA are adequately controlled. The functional benefit in fast-track and laparoscopic surgery needs to be clarified. Better pain control with TEA is established in a wide range of surgical procedures. In a setting of advanced surgical techniques, fast-track regimens and a low overall event rate, the number needed to treat to prevent one death by TEA is high. The risk of harm by TEA is even lower, and other methods used to control perioperative pain and stress response also carry specific risks. To optimize the risk-benefit balance of TEA, safe time intervals regarding the use of concomitant anticoagulants and consideration of reduced renal function impairing their elimination must be observed. Infection is a rare complication and is associated with better prognosis. Close monitoring and a predefined algorithm for the diagnosis and treatment of spinal compression or infection are crucial to ensure patient safety with TEA. The risk-benefit balance of analgesia by TEA is favourable and should foster clinical use. PMID- 22058145 TI - Risk modification of colorectal adenoma by CYP7A1 polymorphisms and the role of bile acid metabolism in carcinogenesis. AB - Cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids, is a postulated gene modifier of colorectal cancer risk and target for the therapeutic bile acid, ursodeoxycholic acid (UDCA). We investigated associations between CYP7A1 polymorphisms and fecal bile acids, colorectal adenoma (CRA), and UDCA efficacy for CRA prevention. Seven tagging, single-nucleotide polymorphisms (SNP) in CYP7A1 were measured in 703 (355 UDCA, 348 placebo) participants of a phase III chemoprevention trial, of which 495 had known baseline fecal bile acid concentrations. In the placebo arm, participants with two minor G(rs8192871) alleles (tag for a low activity promoter polymorphism at -204) had lower odds of high secondary bile acids (OR = 0.26, 95% CI: 0.10-0.69), and CRA at 3 years' follow-up (OR = 0.41, 95% CI: 0.19-0.89), than AA carriers. Haplotype construction from the six polymorphic SNPs showed participants with the third most common haplotype (C(rs10957057)C(rs8192879)G(rs8192877)T(rs11786580)A(rs8192871)G(rs13251096)) had higher odds of high primary bile acids (OR = 2.34, 95% CI: 1.12-4.89) and CRA (OR = 1.89, 95% CI: 1.00-3.57) than those with the most common CTACAG haplotype. Furthermore, three SNPs (rs8192877, rs8192871, and rs13251096) each modified UDCA efficacy for CRA prevention, and CCGTAG-haplotype carriers experienced 71% lower odds of CRA recurrence with UDCA treatment, an effect not present for other haplotypes (test for UDCA-haplotype interaction, P = 0.020). Our findings support CYP7A1 polymorphisms as determinants of fecal bile acids and risk factors for CRA. Furthermore, UDCA efficacy for CRA prevention may be modified by genetic variation in CYP7A1, limiting treatment benefit to a subgroup of the population. PMID- 22058146 TI - A combined array-based comparative genomic hybridization and functional library screening approach identifies mir-30d as an oncomir in cancer. AB - Oncomirs are microRNAs (miRNA) that acts as oncogenes or tumor suppressor genes. Efficient identification of oncomirs remains a challenge. Here we report a novel, clinically guided genetic screening approach for the identification of oncomirs, identifying mir-30d through this strategy. mir-30d regulates tumor cell proliferation, apoptosis, senescence, and migration. The chromosomal locus harboring mir-30d was amplified in more than 30% of multiple types of human solid tumors (n = 1,283). Importantly, higher levels of mir-30d expression were associated significantly with poor clinical outcomes in ovarian cancer patients (n = 330, P = 0.0016). Mechanistic investigations suggested that mir-30d regulates a large number of cancer-associated genes, including the apoptotic caspase CASP3. The guided genetic screening approach validated by this study offers a powerful tool to identify oncomirs that may have utility as biomarkers or targets for drug development. PMID- 22058147 TI - Defective NF-kappaB signaling in metastatic head and neck cancer cells leads to enhanced apoptosis by double-stranded RNA. AB - Ligands to several Toll-like receptors (TLR), which mediate innate immune responses and chronic inflammation have been used as adjuvants to immunotherapy to enhance their antitumor activity. In particular, double-stranded RNAs that are cognate ligands of TLR3 have been used to trigger proapoptotic activity in cancer cells. However, a mechanistic understanding of TLR3-mediated apoptosis and its potential involvement in controlling tumor metastasis has been lacking. In this study, we used paired cell lines and fresh tumor specimens, derived from autologous primary and metastatic head and neck squamous cell carcinoma, to investigate the role of TLR3 signaling in metastatic progression. Compared with primary tumor cells, metastatic tumor cells were highly sensitive to TLR3 mediated apoptosis after double-stranded RNA treatment. Enhanced apoptosis in metastatic cells was dependent on double-stranded RNA and TLR3 and also the TLR3 effector signaling protein TRIF. Downstream responses requiring NF-kappaB were critical for apoptosis in metastatic cells, the defects in which could be resuscitated by alternative pathways of NF-kappaB activation. By elucidating how TLR3 ligands trigger apoptosis in metastatic cells, our findings suggest insights into how to improve their clinical use. PMID- 22058148 TI - Angiopoietin-2 promotes inflammatory lymphangiogenesis and its effect can be blocked by the specific inhibitor L1-10. AB - Angiopoietin (Ang)-2, a ligand of the receptor tyrosine kinase Tie2, is known to be involved in the regulation of embryonic lymphangiogenesis. However, the role of Ang-2 in postnatal pathological lymphangiogenesis, such as inflammation, is largely unknown. We used a combination of imaging, molecular, and cellular approaches to investigate whether Ang-2 is involved in inflammatory lymphangiogenesis. We observed strong and continuous expression of Ang-2 on newly generated lymphatic vessels for 2 wk in sutured corneas of BALB/c mice. This expression was concurrent with an increased number of lymphatic vessels. TNF alpha expression also increased, with peak TNF-alpha expression occurring before peak Ang-2 expression was reached. In vitro experiments showed that TNF-alpha stimulates Ang-2 and Tie2 and ICAM-1 expression on human lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs). Ang-2 alone did not affect the biological behavior of LECs, whereas Ang-2 combined with TNF-alpha significantly promoted the proliferation of LECs but not BECs. In mouse models, blockade of Ang-2 with L1-10, an Ang-2-specific inhibitor, significantly inhibited lymphangiogenesis but promoted angiogenesis. These results clearly indicate that Ang-2 acts as a crucial regulator of inflammatory lymphangiogenesis by sensitizing the lymphatic vasculature to inflammatory stimuli, thereby directly promoting lymphangiogenesis. The involvement of Ang-2 in inflammatory lymphangiogenesis provides a strong rationale for the exploitation of anti-Ang-2 treatment in the prevention and treatment of tumor metastasis and transplant rejection. PMID- 22058149 TI - Diabetes-induced vascular dysfunction involves arginase I. AB - Arginase can cause vascular dysfunction by competing with nitric oxide synthase for l-arginine and by increasing cell proliferation and collagen formation, which promote vascular fibrosis/stiffening. We have shown that increased arginase expression/activity contribute to vascular endothelial cell (EC) dysfunction. Here, we examined the roles of the two arginase isoforms, arginase I and II (AI and AII, respectively), in this process. Experiments were performed using streptozotocin-induced diabetic mice: wild-type (WT) mice and knockout mice lacking the AII isoform alone (AI(+/+)AII(-/-)) or in combination with partial deletion of AI (AI(+/-)AII (-/-)). EC-dependent vasorelaxation of aortic rings and arterial fibrosis and stiffness were assessed in relation to arginase activity and expression. Diabetes reduced mean EC-dependent vasorelaxation markedly in diabetic WT and AI(+/+)AII(-/-) aortas (53% and 44% vs. controls, respectively) compared with a 27% decrease in AI(+/-)AII (-/-) vessels. Coronary fibrosis was also increased in diabetic WT and AI(+/+)AII(-/-) mice (1.9- and 1.7 fold vs. controls, respectively) but was not altered in AI(+/-)AII (-/-) diabetic mice. Carotid stiffness was increased by 142% in WT diabetic mice compared with 51% in AI(+/+)AII(-/-) mice and 19% in AI(+/-)AII (-/-) mice. In diabetic WT and AI(+/+)AII(-/-) mice, aortic arginase activity and AI expression were significantly increased compared with control mice, but neither parameter was altered in AI(+/-)AII (-/-) mice. In summary, AI(+/-)AII (-/-) mice exhibit better EC-dependent vasodilation and less vascular stiffness and coronary fibrosis compared with diabetic WT and AI(+/+)AII(-/-) mice. These data indicate a major involvement of AI in diabetes-induced vascular dysfunction. PMID- 22058150 TI - Role of soluble adenylyl cyclase in the heart. AB - This review discusses the potential place of soluble adenylyl cyclase (sAC) in the framework of signaling in the cardiovascular system. cAMP has been studied as a critical and pleiotropic second messenger in cardiomyocytes, endothelial cells, and smooth muscle vascular cells for many years. It is involved in the transduction of signaling by catecholamines, prostaglandins, adenosine, and glucagon, just to name a few. These hormones can act via cAMP by binding to a G protein-coupled receptor on the plasma membrane with subsequent activation of a heterotrimeric G protein and its downstream effector, transmembrane adenylyl cyclase. This has long been the canonical standard for cAMP production in a cell. However, the relatively recent discovery of a unique source of cAMP, sAC, creates the potential for a shift in this signaling paradigm. In fact, sAC has been shown to play a role in apoptosis in coronary endothelial cells and cardiomyocytes. Additionally, it links nutrient utilization with ATP production in the liver and brain, which suggests one of many potential roles for sAC in cardiac function. The possibility of producing cAMP from a source distal to the plasma membrane provides a critical new building block for reconstructing the cellular signaling infrastructure. PMID- 22058151 TI - Chronic Akt blockade aggravates pathological hypertrophy and inhibits physiological hypertrophy. AB - The attenuation of adverse myocardial remodeling and pathological left ventricular (LV) hypertrophy is one of the hallmarks for improving the prognosis after myocardial infarction (MI). The protein kinase Akt plays a central role in regulating cardiac hypertrophy, but the in vivo effects of chronic pharmacological inhibition of Akt are unknown. We investigated the effect of chronic Akt blockade with deguelin on the development of pathological [MI and aortic banding (AB)] and physiological (controlled treadmill running) hypertrophy. Primary cardiomyocyte cultures were incubated with 10 MUmol deguelin for 48 h, and Wistar rats were treated orally with deguelin (4.0 mg.kg(-1).day( 1)) for 4 wk starting 1 day after the induction of MI or AB. Exercise-trained animals received deguelin for 4 wk during the training period. In vitro, we observed reduced phosphorylation of Akt and glycogen synthase kinase (GSK)-3beta after an incubation with deguelin, whereas MAPK signaling was not significantly affected. In vivo, treatment with deguelin led to attenuated phosphorylation of Akt and GSK-3beta 4 wk after MI. These animals showed significantly increased heart weights and impaired LV function with increased end-diastolic diameters (12.0 +/- 0.3 vs. 11.1 +/- 0.3 mm, P < 0.05), end-diastolic volumes (439 +/- 8 vs. 388 +/- 18 MUl, P < 0.05), and cardiomyocyte sizes (+20%, P < 0.05) compared with MI animals receiving vehicle treatment. Furthermore, activation of Ca(2+)/calmodulin-dependent kinase II in deguelin-treated MI animals was increased compared with the vehicle-treated group. Four wk after AB, we observed an augmentation of pathological hypertrophy in the deguelin-treated group with a significant increase in heart weights and cardiomyocyte sizes (>20%, P < 0.05). In contrast, the development of physiological hypertrophy was inhibited by deguelin treatment in exercise-trained animals. In conclusion, chronic Akt blockade with deguelin aggravates adverse myocardial remodeling and antagonizes physiological hypertrophy. PMID- 22058152 TI - Morelloflavone, a biflavonoid inhibitor of migration-related kinases, ameliorates atherosclerosis in mice. AB - While macrophages take up modified LDL to form foam cells and multiply to develop fatty streaks, vascular smooth muscle cells (VSMC) migrate from the media to intima, secrete extracellular matrix, and increase the volume of atherosclerotic lesions. A medicinal plant Garcinia dulcis has been used in traditional Thai medicine for centuries to treat various chronic human diseases. Morelloflavone, a biflavonoid and an active ingredient of the plant, has been shown to inhibit VSMC migration through its inhibition of multiple migration-related kinases such as focal adhesion kinase, c-Src, ERK, and RhoA. However, the exact role of morelloflavone in atherosclerogenesis was unknown. We fed Ldlr(-/-)Apobec1(-/-) mice with either normal chow or chow containing 0.003% morelloflavone for 8 mo and assessed the extent of atherosclerosis by the en face and cross-sectional analyses. A cell composition analysis of atherosclerotic tissue was carried out using immunohistochemical staining. Oral morelloflavone therapy significantly reduced the atherosclerotic areas of the mouse aortas (a 26% reduction), without changing plasma lipid profiles or weights. Immunohistochemical analyses showed that morelloflavone reduced the number of VSMC in the atherosclerotic lesion while it did not change the density of macrophages in the lesion or the percentages of proliferating and apoptotic cells. Oral, low-dose, morelloflavone therapy retards atherosclerogenesis by limiting the migration of VSMC into the intima in the mouse model of human atherosclerosis. Upon further investigation, morelloflavone may be found to be a novel oral antiatherosclerotic agent and a viable addition to the conventional therapies such as statins in humans. PMID- 22058153 TI - The PTPN11 loss-of-function mutation Q510E-Shp2 causes hypertrophic cardiomyopathy by dysregulating mTOR signaling. AB - The identification of mutations in PTPN11 (encoding the protein tyrosine phosphatase Shp2) in families with congenital heart disease has facilitated mechanistic studies of various cardiovascular defects. However, the roles of normal and mutant Shp2 in the developing heart are still poorly understood. Furthermore, it remains unclear how Shp2 loss-of-function (LOF) mutations cause LEOPARD Syndrome (also termed Noonan Syndrome with multiple lentigines), which is characterized by congenital heart defects such as pulmonary valve stenosis and hypertrophic cardiomyopathy (HCM). In normal hearts, Shp2 controls cardiomyocyte size by regulating signaling through protein kinase B (Akt) and mammalian target of rapamycin (mTOR). We hypothesized that Shp2 LOF mutations dysregulate this pathway, resulting in HCM. For our studies, we chose the Shp2 mutation Q510E, a dominant-negative LOF mutation associated with severe early onset HCM. Newborn mice with cardiomyocyte-specific overexpression of Q510E-Shp2 starting before birth displayed increased cardiomyocyte sizes, heart-to-body weight ratios, interventricular septum thickness, and cardiomyocyte disarray. In 3-mo-old hearts, interstitial fibrosis was detected. Echocardiographically, ventricular walls were thickened and contractile function was depressed. In ventricular tissue samples, signaling through Akt/mTOR was hyperactivated, indicating that the presence of Q510E-Shp2 led to upregulation of this pathway. Importantly, rapamycin treatment started shortly after birth rescued the Q510E-Shp2-induced phenotype in vivo. If rapamycin was started at 6 wk of age, HCM was also ameliorated. We also generated a second mouse model in which cardiomyocyte specific Q510E-Shp2 overexpression started after birth. In contrast to the first model, these mice did not develop HCM. In summary, our studies establish a role for mTOR signaling in HCM caused by Q510E-Shp2. Q510E-Shp2 overexpression in the cardiomyocyte population alone was sufficient to induce the phenotype. Furthermore, the pathomechanism was triggered pre- but not postnatally. However, postnatal rapamycin treatment could still reverse already established HCM, which may have important therapeutic implications. PMID- 22058155 TI - Displacement-encoded and manganese-enhanced cardiac MRI reveal that nNOS, not eNOS, plays a dominant role in modulating contraction and calcium influx in the mammalian heart. AB - Within cardiomyocytes, endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) are thought to modulate L-type calcium channel (LTCC) function and sarcoplasmic reticulum calcium cycling, respectively. However, divergent results from mostly invasive prior studies suggest more complex roles. To elucidate the roles of nNOS and eNOS in vivo, we applied noninvasive cardiac MRI to study wild-type (WT), eNOS(-/-), and nNOS(-/-) mice. An in vivo index of LTCC flux (LTCCI) was measured at baseline (Bsl), dobutamine (Dob), and dobutamine + carbacholamine (Dob + CCh) using manganese-enhanced MRI. Displacement-encoded MRI assessed contractile function by measuring circumferential strain (E(cc)) and systolic (dE(cc)/dt) and diastolic (dE(cc)/dt(diastolic)) strain rates at Bsl, Dob, and Dob + CCh. Bsl LTCCI was highest in nNOS(-/-) mice (P < 0.05 vs. WT and eNOS(-/-)) and increased only in WT and eNOS(-/-) mice with Dob (P < 0.05 vs. Bsl). LTCCI decreased significantly from Dob levels with Dob + CCh in all mice. Contractile function, as assessed by E(cc), was similar in all mice at Bsl. With Dob, E(cc) increased significantly in WT and eNOS(-/-) but not nNOS(-/-) mice (P < 0.05 vs. WT and eNOS(-/-)). With Dob + CCh, E(cc) returned to baseline levels in all mice. Systolic blood pressure, measured via tail plethysmography, was highest in eNOS(-/-) mice (P < 0.05 vs. WT and nNOS(-/-)). Mice deficient in nNOS demonstrate increased Bsl LTCC function and an attenuated contractile reserve to Dob, whereas eNOS(-/-) mice demonstrate normal LTCC and contractile function under all conditions. These results suggest that nNOS, not eNOS, plays the dominant role in modulating Ca(2+) cycling in the heart. PMID- 22058154 TI - How NaCl raises blood pressure: a new paradigm for the pathogenesis of salt dependent hypertension. AB - Excess dietary salt is a major cause of hypertension. Nevertheless, the specific mechanisms by which salt increases arterial constriction and peripheral vascular resistance, and thereby raises blood pressure (BP), are poorly understood. Here we summarize recent evidence that defines specific molecular links between Na(+) and the elevated vascular resistance that directly produces high BP. In this new paradigm, high dietary salt raises cerebrospinal fluid [Na(+)]. This leads, via the Na(+)-sensing circumventricular organs of the brain, to increased sympathetic nerve activity (SNA), a major trigger of vasoconstriction. Plasma levels of endogenous ouabain (EO), the Na(+) pump ligand, also become elevated. Remarkably, high cerebrospinal fluid [Na(+)]-evoked, locally secreted (hypothalamic) EO participates in a pathway that mediates the sustained increase in SNA. This hypothalamic signaling chain includes aldosterone, epithelial Na(+) channels, EO, ouabain-sensitive alpha(2) Na(+) pumps, and angiotensin II (ANG II). The EO increases (e.g.) hypothalamic ANG-II type-1 receptor and NADPH oxidase and decreases neuronal nitric oxide synthase protein expression. The aldosterone epithelial Na(+) channel-EO-alpha(2) Na(+) pump-ANG-II pathway modulates the activity of brain cardiovascular control centers that regulate the BP set point and induce sustained changes in SNA. In the periphery, the EO secreted by the adrenal cortex directly enhances vasoconstriction via an EO-alpha(2) Na(+) pump Na(+)/Ca(2+) exchanger-Ca(2+) signaling pathway. Circulating EO also activates an EO-alpha(2) Na(+) pump-Src kinase signaling cascade. This increases the expression of the Na(+)/Ca(2+) exchanger-transient receptor potential cation channel Ca(2+) signaling pathway in arterial smooth muscle but decreases the expression of endothelial vasodilator mechanisms. Additionally, EO is a growth factor and may directly participate in the arterial structural remodeling and lumen narrowing that is frequently observed in established hypertension. These several central and peripheral mechanisms are coordinated, in part by EO, to effect and maintain the salt-induced elevation of BP. PMID- 22058156 TI - Current perspectives on cardiac amyloidosis. AB - Amyloidosis represents a group of diseases in which proteins undergo misfolding to form insoluble fibrils with subsequent tissue deposition. While almost all deposited amyloid fibers share a common nonbranched morphology, the affected end organs, clinical presentation, treatment strategies, and prognosis vary greatly among this group of diseases and are largely dependent on the specific amyloid precursor protein. To date, at least 27 precursor proteins have been identified to result in either local tissue or systemic amyloidosis, with nine of them manifesting in cardiac deposition and resulting in a syndrome termed "cardiac amyloidosis" or "amyloid cardiomyopathy." Although cardiac amyloidosis has been traditionally considered to be a rare disorder, as clinical appreciation and understanding continues to grow, so too has the prevalence, suggesting that this disease may be greatly underdiagnosed. The most common form of cardiac amyloidosis is associated with circulating amyloidogenic monoclonal immunoglobulin light chain proteins. Other major cardiac amyloidoses result from a misfolding of products of mutated or wild-type transthyretin protein. While the various cardiac amyloidoses share a common functional consequence, namely, an infiltrative cardiomyopathy with restrictive pathophysiology leading to progressive heart failure, the underlying pathophysiology and clinical syndrome varies with each precursor protein. Herein, we aim to provide an up-to-date overview of cardiac amyloidosis from nomenclature to molecular mechanisms and treatment options, with a particular focus on amyloidogenic immunoglobulin light chain protein cardiac amyloidosis. PMID- 22058157 TI - Electromechanical feedback with reduced cellular connectivity alters electrical activity in an infarct injured left ventricle: a finite element model study. AB - Myocardial infarction (MI) significantly alters the structure and function of the heart. As abnormal strain may drive heart failure and the generation of arrhythmias, we used computational methods to simulate a left ventricle with an MI over the course of a heartbeat to investigate strains and their potential implications to electrophysiology. We created a fully coupled finite element model of myocardial electromechanics consisting of a cellular physiological model, a bidomain electrical diffusion solver, and a nonlinear mechanics solver. A geometric mesh built from magnetic resonance imaging (MRI) measurements of an ovine left ventricle suffering from a surgically induced anteroapical infarct was used in the model, cycled through the cardiac loop of inflation, isovolumic contraction, ejection, and isovolumic relaxation. Stretch-activated currents were added as a mechanism of mechanoelectric feedback. Elevated fiber and cross fiber strains were observed in the area immediately adjacent to the aneurysm throughout the cardiac cycle, with a more dramatic increase in cross fiber strain than fiber strain. Stretch-activated channels decreased action potential (AP) dispersion in the remote myocardium while increasing it in the border zone. Decreases in electrical connectivity dramatically increased the changes in AP dispersion. The role of cross fiber strain in MI-injured hearts should be investigated more closely, since results indicate that these are more highly elevated than fiber strain in the border of the infarct. Decreases in connectivity may play an important role in the development of altered electrophysiology in the high stretch regions of the heart. PMID- 22058158 TI - Phosphodiesterase type-2 and NO-dependent S-nitrosylation mediate the cardioinhibition of the antihypertensive catestatin. AB - The chromogranin A (CHGA)-derived peptide catestatin (CST: hCHGA(352-372)) is a noncompetitive catecholamine-release inhibitor that exerts vasodilator, antihypertensive, and cardiosuppressive actions. We have shown that CST directly influences the basal performance of the vertebrate heart where CST dose dependently induced a nitric oxide-cGMP-dependent cardiosuppression and counteracted the effects of adrenergic stimulation through a noncompetitive antagonism. Here, we sought to determine the specific intracardiac signaling activated by CST in the rat heart. Physiological analyses performed on isolated, Langendorff-perfused cardiac preparations revealed that CST-induced negative inotropism and lusitropism involve beta(2)/beta(3)-adrenergic receptors (beta(2)/beta(3)-AR), showing a higher affinity for beta(2)-AR. Interaction with beta(2)-AR activated phosphatidylinositol 3-kinase/endothelial nitric oxide synthase (eNOS), increased cGMP levels, and induced activation of phosphodiesterases type 2 (PDE2), which was found to be involved in the antiadrenergic action of CST as evidenced by the decreased cAMP levels. CST dependent negative cardiomodulation was abolished by functional denudation of the endothelium with Triton. CST also increased the eNOS expression in cardiac tissue and human umbilical vein endothelial cells. cells, confirming the involvement of the vascular endothelium. In ventricular extracts, CST increased S-nitrosylation of both phospholamban and beta-arrestin, suggesting an additional mechanism for intracellular calcium modulation and beta-adrenergic responsiveness. We conclude that PDE2 and S-nitrosylation play crucial roles in the CST regulation of cardiac function. Our results are of importance in relation to the putative application of CST as a cardioprotective agent against stress, including excessive sympathochromaffin overactivation. PMID- 22058159 TI - Differential effect of atorvastatin and tacrolimus on proliferation of vascular smooth muscle and endothelial cells. AB - Although considered promising for use in drug-eluting stents (DES), tacrolimus failed clinically. Tacrolimus inhibits growth factor production but can also act as a growth factor on vascular smooth muscle cells (VSMC). This unexpected proliferative stimulus could reverse the beneficial effects of the drug on restenosis. We hypothesized that tacrolimus' association with statins, which lower cholesterol and impair cell proliferation, could restore tacrolimus' beneficial effect by abrogating the aberrant proliferative stimulus. Additionally, since maintenance of endothelial function represents a challenge for new-generation DES, we investigated the combined effect of tacrolimus and atorvastatin on endothelial cells. Human VSMC and umbilical vein endothelial cells (HUVEC) were incubated with 100 nM tacrolimus and increasing doses of atorvastatin (0-3.0 MUM). Atorvastatin plus tacrolimus dose-dependently inhibited VSMC proliferation. The percentage of cells incorporating 5-bromo-2'-deoxyuridine (BrdU) in their DNA was 49 +/- 14% under basal conditions, 62 +/- 15% (P = 0.01) with tacrolimus, 40 +/- 22% with 3 MUM atorvastatin, and 30 +/- 7% (P < 0.05) with 3 MUM atorvastatin plus tacrolimus. Atorvastatin downregulated beta-catenin, Erk1 and Erk2, and cyclin B in tacrolimus-stimulated VSMC. In contrast, atorvastatin plus tacrolimus did not affect proliferation of endothelial cells. The percentage of HUVEC incorporating BrdU in their DNA was 47 +/- 8% under basal conditions, 58 +/- 6% (P = 0.01) with tacrolimus, 45 +/- 4% with 3 MUM atorvastatin, and 49 +/- 1% with 3 MUM atorvastatin plus tacrolimus. Both agents stimulated endoglin production by HUVEC. Taken together, these results suggest that, when combined with tacrolimus, atorvastatin exerts a dose-dependent antiproliferative effect on VSMC. In contrast, atorvastatin acts in concert with tacrolimus in HUVEC to stimulate production of endoglin, a factor that has an important role in endothelial repair. Our study supports the conclusion that prevention of postcoronary in-stent restenosis and late thrombosis may benefit of concomitant association of tacrolimus and high doses of atorvastatin. PMID- 22058160 TI - Contribution of arterial blood pressure and PaCO2 to the cerebrovascular responses to motor stimulation. AB - Motor stimulation induces a neurovascular response that can be detected by continuous measurement of cerebral blood flow (CBF). Simultaneous changes in arterial blood pressure (ABP) and Pa(CO(2)) have been reported, but their influence on the CBF response has not been quantified. Continuous bilateral recordings of CBF velocity (CBFV), ABP, and end-tidal CO(2) (ET(CO(2))) were obtained in 10 healthy middle-aged subjects at rest and during 60 s of repetitive, metronome-controlled (1 Hz) elbow flexion. A multivariate autoregressive-moving average model was adopted to quantify the relationship between beat-to-beat changes in ABP, breath-by-breath ET(CO(2)), and the motor stimulus, represented by the metronome on-off signal (inputs), and the CBFV response to stimulation (output). All three inputs contributed to explain CBFV variance following stimulation. For the ipsi- and contralateral hemispheres, ABP explained 20.3 +/- 17.3% (P = 0.0007) and 19.5 +/- 17.2% (P = 0.01) of CBFV variance, respectively. Corresponding values for ET(CO(2)) and metronome signals were 22.0 +/- 24.2% (P = 0.008), 24.0 +/- 24.1% (P = 0.037), 32.7 +/- 22.5% (P = 0.0015), and 43.2 +/- 25.1% (P = 0.013), respectively. Synchronized population averages suggest that the initial sudden change in CBFV was largely due to ABP, while the influence of ET(CO(2)) was more erratic. The component due to elbow flexion showed a well-defined pattern, with rise time slower than the main CBFV change but reaching a stable plateau after 15 s of stimulation. Identifying and removing the influences of ABP and Pa(CO(2)) to motor-induced changes in CBF should lead to more robust estimates of neurovascular coupling and better understanding of its physiological covariates. PMID- 22058161 TI - Molecular chaperones and heat shock proteins in atherosclerosis. AB - In response to stress stimuli, mammalian cells activate an ancient signaling pathway leading to the transient expression of heat shock proteins (HSPs). HSPs are a family of proteins serving as molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures. Physiologically, HSPs play a protective role in the homeostasis of the vessel wall but have an impact on immunoinflammatory processes in pathological conditions involved in the development of atherosclerosis. For instance, some members of HSPs have been shown to have immunoregulatory properties and modification of innate and adaptive response to HSPs, and can protect the vessel wall from the disease. On the other hand, a high degree of sequence homology between microbial and mammalian HSPs, due to evolutionary conservation, carries a risk of misdirected autoimmunity against HSPs expressed on the stressed cells of vascular endothelium. Furthermore, HSPs and anti-HSP antibodies have been shown to elicit production of proinflammatory cytokines. Potential therapeutic use of HSP in prevention of atherosclerosis involves achieving optimal balance between protective and immunogenic effects of HSPs and in the progress of research on vaccination. In this review, we update the progress of studies on HSPs and the integrity of the vessel wall, discuss the mechanism by which HSPs exert their role in the disease development, and highlight the potential clinic translation in the research field. PMID- 22058162 TI - Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice. AB - Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (epsilon2, epsilon3, and epsilon4) reflecting single amino acid substitutions at amino acids 112 and 158. The objective of this study was to assess whether the human apoE alleles modify airway responses to repeated nasal HDM challenges. Mice expressing the human apoE epsilon2 (huApoE2), epsilon3 (huApoE3), or epsilon4 (huApoE4) alleles received nasal HDM challenges, and airway responses were compared with mice expressing the endogenous murine apoE gene (muApoE). huApoE3 mice displayed significant reductions in AHR, mucous cell metaplasia, and airway inflammation compared with muApoE mice. The attenuated severity of airway inflammation in huApoE3 mice was associated with reductions in lung mRNA levels of Th2 and Th17 cytokines, as well as chemokines (CCL7, CCL11, CCL24). huApoE4 mice had an intermediate phenotype, with attenuated AHR and IgE production, compared with muApoE mice, whereas airway inflammation and mucous cell metaplasia were not reduced. In contrast, HDM induced airway responses were not modified in mice expressing the huApoE2 allele. We conclude that the polymorphic huApoE alleles differentially modulate HDM induced airway disease, which can be stratified, in rank order of increasing disease severity, epsilon3 < epsilon4 < epsilon2. These results raise the possibility that the polymorphic apoE alleles may modify disease severity in human asthma. PMID- 22058166 TI - The exercise pressor reflex in animals. AB - This report summarizes work concerning the exercise pressor reflex performed in my laboratory over the past 20 years or so. It is part of a symposium held to celebrate the 40th anniversary of two publications by Dr Jere Mitchell that appeared in The Journal of Physiology. For the most part, this report concerns itself with the discharge properties of group III and IV muscle afferents. Particular attention has been paid to their responses to arterial injection of putative metabolic byproducts of muscular contraction as well as their responses to both static contraction and dynamic exercise. PMID- 22058167 TI - Muscle afferent activation causes ventilatory and cardiovascular responses during concurrent hypercapnia in humans. AB - Respiratory and cardiovascular responses to muscle mechanoreflex (passive calf stretch) and metaboreflex activation (local circulatory occlusion) were examined during inhalation of a hypercapnic gas mixture in four trials. These controlled for the effects of central command, metabolite sensitization of muscle afferents and hypercapnia-induced elevation of central respiratory drive. In an isokinetic dynamometer, with circulation through the right leg occluded by inflation of a thigh cuff, 13 participants either rested (control trial; CON) or plantarflexed their ankle at 50% maximal force for 1.5 min (voluntary exercise trial; EX). Thereafter, circulatory occlusion was maintained and the calf passively stretched before return to the resting position. Both trials were performed while breathing air, as well as while breathing a normoxic, hypercapnic (5% CO(2)) gas mixture (CO(2) trial and CO(2)+EX trial). Hypercapnic gas inhalation increased baseline minute ventilation (V), heart rate and mean arterial pressure (+27.67 +/- 1.74 l min(-1), +7 +/- 0.85 beats min(-1) and +13 +/- 3.41 mmHg, respectively; means +/- SEM) above control values (9.78 +/- 0.86 l min(-1), 62 +/- 2.3 beats min(-1) and 88 +/- 2.6 mmHg, respectively). Voluntary exercise further increased these variables from baseline during both trials (P < 0.05). During the continued circulatory occlusion after voluntary exercise, mean arterial pressure remained significantly elevated (P < 0.05). Minute ventilation returned to baseline during circulatory occlusion following exercise in the EX trial, but in the CO(2)+EX trial the V remained elevated at end-exercise levels during this period (+7.12 +/ 1.13 l min(-1)). Passive stretch caused further increases in V during CO(2)+EX and CO(2) trials but not in CON and EX. These results indicate that in the absence of central command, either muscle metaboreflex and/or mechanoreflex activation stimulates ventilation during concurrent hypercapnia. PMID- 22058168 TI - Exercise training attenuates the hypermuscular phenotype and restores skeletal muscle function in the myostatin null mouse. AB - Myostatin regulates both muscle mass and muscle metabolism. The myostatin null (MSTN(-/-)) mouse has a hypermuscular phenotype owing to both hypertrophy and hyperplasia of the myofibres. The enlarged muscles display a reliance on glycolysis for energy production; however, enlarged muscles that develop in the absence of myostatin have compromised force-generating capacity. Recent evidence has suggested that endurance exercise training increases the oxidative properties of muscle. Here, we aimed to identify key changes in the muscle phenotype of MSTN(-/-) mice that can be induced by training. To this end, we subjected MSTN(-/ ) mice to two different forms of training, namely voluntary wheel running and swimming, and compared the response at the morphological, myocellular and molecular levels. We found that both regimes normalized changes of myostatin deficiency and restored muscle function. We showed that both exercise training regimes increased muscle capillary density and the expression of Ucp3, Cpt1alpha, Pdk4 and Errgamma, key markers for oxidative metabolism. Cross-sectional area of hypertrophic myofibres from MSTN(-/-) mice decreased towards wild-type values in response to exercise and, in this context, Bnip3, a key autophagy-related gene, was upregulated. This reduction in myofibre size caused an increase of the nuclear-to-cytoplasmic ratio towards wild-type values. Importantly, both training regimes increased muscle force in MSTN(-/-) mice. We conclude that impaired skeletal muscle function in myostatin-deficient mice can be improved through endurance exercise-mediated remodelling of muscle fibre size and metabolic profile. PMID- 22058169 TI - The financial impact of health information exchange on emergency department care. AB - OBJECTIVE: To examine the financial impact health information exchange (HIE) in emergency departments (EDs). MATERIALS AND METHODS: We studied all ED encounters over a 13-month period in which HIE data were accessed in all major emergency departments Memphis, Tennessee. HIE access encounter records were matched with similar encounter records without HIE access. Outcomes studied were ED-originated hospital admissions, admissions for observation, laboratory testing, head CT, body CT, ankle radiographs, chest radiographs, and echocardiograms. Our estimates employed generalized estimating equations for logistic regression models adjusted for admission type, length of stay, and Charlson co-morbidity index. Marginal probabilities were used to calculate changes in outcome variables and their financial consequences. RESULTS: HIE data were accessed in approximately 6.8% of ED visits across 12 EDs studied. In 11 EDs directly accessing HIE data only through a secure Web browser, access was associated with a decrease in hospital admissions (adjusted odds ratio (OR)=0.27; p<0001). In a 12th ED relying more on print summaries, HIE access was associated with a decrease in hospital admissions (OR=0.48; p<0001) and statistically significant decreases in head CT use, body CT use, and laboratory test ordering. DISCUSSION: Applied only to the study population, HIE access was associated with an annual cost savings of $1.9 million. Net of annual operating costs, HIE access reduced overall costs by $1.07 million. Hospital admission reductions accounted for 97.6% of total cost reductions. CONCLUSION: Access to additional clinical data through HIE in emergency department settings is associated with net societal saving. PMID- 22058170 TI - Time points may also count in assessment of the difference between prescribed and delivered dose. PMID- 22058171 TI - The reason why mother nature provided us with two kidneys: the risks of a congenital solitary functioning kidney. PMID- 22058172 TI - Effect of steroid-free low concentration calcineurin inhibitor maintenance immunosuppression regimen on renal allograft histopathology and function. AB - BACKGROUND: The most common cause of late kidney transplant failure is insidiously progressive renal dysfunction associated with organ scarring and fibrosis. Advanced donor age, delayed graft function, calcineurin toxicity and repeated acute rejection episodes are risk factors for this pathophysiology. METHODS: We employed 3, 12 and 24 months surveillance renal biopsies, scored using the Chronic Allograft Damage Index (CADI), with periodic estimates of glomerular filtration rate (eGFR) to assess the effect of a steroid-free maintenance immunosuppression regimen on allograft histology and function. Ninety one patients were induced with Alemtuzumab and then treated with mycophenolate sodium and low trough concentrations of tacrolimus. RESULTS: Fifty-six of 91 patients followed for 24 months showed no clinical rejection and in 16 more only minimal histological or borderline changes as defined by Banff criteria were observed. Histologically acute rejection was observed in 14 patients including two detected on surveillance biopsy. Five patients refused biopsies but showed stable eGFR for 24 months. Graft histopathology in the group with no rejection did not worsen. In contrast, nearly half the patients with acute rejection showed progression of CADI scores and a total of four grafts were lost over the 2 years. The 16 patients with borderline rejection changes exhibited stable glomerular filtration rate throughout, but 12.5% showed progression of CADI scores in the 12 to 24-month period. CONCLUSIONS: Following Alemtuzumab induction and in conjunction with low-dose tacrolimus and mycophenolate, continuous steroid therapy was not required to prevent progressive injury or preservation of graft function in patients without biopsy-proven acute rejection. Scored surveillance renal biopsies provide a useful tool to monitor transplanted kidneys. PMID- 22058173 TI - Suppression of neointimal hyperplasia by sirolimus-eluting expanded polytetrafluoroethylene (ePTFE) haemodialysis grafts in comparison with paclitaxel-coated grafts. AB - BACKGROUND: Haemodialysis vascular access dysfunction caused by aggressive venous neointimal hyperplasia is a major problem for haemodialysis patients with synthetic arteriovenous (AV) grafts. Several different strategies to prevent venous stenosis by inhibiting smooth muscle cell proliferation and migration using local delivery of potent antiproliferative agents are currently under investigation. We performed this study to evaluate the efficacy of sirolimus eluting vascular grafts in preventing stenosis and to compare the effectiveness of sirolimus-coated grafts with that of paclitaxel-coated vascular grafts that we characterized in a previous study. METHODS: AV grafts were implanted laterally between the common carotid artery and external jugular vein of 14 female Landrace pigs. Three types of grafts were implanted: grafts coated with 1.08 MUg/mm(2) sirolimus (low dose, n = 6), grafts coated with 2.41 MUg/mm(2) sirolimus (high dose, n = 2) and uncoated control grafts (n = 6). Animals were sacrificed 6 weeks after surgery. Cross-sections of the venous anastomoses were analysed to determine the percentage of luminal stenosis in each group, and immunohistochemistry was performed to identify the cellular phenotypes of the neointimal hyperplasia and tissues adjacent to the implanted grafts. RESULTS: Compared with the control group, neointimal hyperplasia in the venous anastomoses of the groups implanted with sirolimus-coated vascular grafts was significantly suppressed without infection. The mean +/- standard error values for the percentage of luminal stenosis were 75.7 +/- 12.7% in the control group and 22.2 +/- 1.41% in the low-dose sirolimus-coated group. Myofibroblasts and fibroblasts were the major cell types found in the neointimal hyperplasia. CONCLUSIONS: Neointimal hyperplasia was effectively suppressed by sirolimus-eluting grafts. However, the inhibitory effects of sirolimus-eluting grafts were weaker than those observed for paclitaxel-coated grafts in our previous study. PMID- 22058174 TI - Psychosocial variables are associated with being wait-listed, but not with receiving a kidney transplant in the Dialysis Outcomes and Practice Patterns Study (DOPPS). AB - BACKGROUND: Psychosocial factors are associated with clinical outcomes in patients with end-stage renal disease. It is not known if self-reported depression and quality of life influence the likelihood of being wait-listed and receiving a transplant. METHODS: Prevalent cross section of 18- to 65-year-old hemodialysis (HD) patients in the USA (N = 2033) and seven European countries (N = 4350) from the Dialysis Outcomes and Practice Patterns Study phase II and III was analyzed. Wait-listed patients (N = 1838) were followed until kidney transplantation. Self-reported depressive symptoms were assessed by the Center for Epidemiologic Studies-Depression scale, 10-item version (CES-D) and health related quality of life (HR-QoL) by the Kidney Disease Quality of Life Short Form 12 scale Physical Component Score (PCS). RESULTS: At study entry, 27% (USA) to 53% (UK) of patients were wait-listed in participating countries. Variables associated with lower odds of being on the waiting list included worse HR-QoL, more severe depressive symptoms, older age, fewer years of education, lower serum albumin, lower hemoglobin, shorter time on dialysis and presence of multiple comorbid conditions. Among wait-listed patients, significantly lower transplantation rates were seen for females, blacks, patients having prior transplantation and multiple comorbid conditions but not PCS or CES-D. CONCLUSIONS: Fewer depressive symptoms and better HR-QoL are associated with being on the waiting list in prevalent HD patients but not with receiving a kidney transplant among wait-listed dialysis patients. Regular assessment of subjective well-being may help identify patients with reduced access to wait listing and kidney transplantation. PMID- 22058175 TI - Rostral overnight fluid shift in end-stage renal disease: relationship with obstructive sleep apnea. AB - BACKGROUND: In both healthy male subjects and men with heart failure, the severity of obstructive sleep apnea (OSA) is related to the amount of fluid displaced from their legs into the neck overnight. Whether overnight rostral fluid shift contributes to the pathogenesis of OSA in patients with end-stage renal disease (ESRD) is unknown. We hypothesized that the change in neck circumference (NC) and severity of OSA are related to the extent of overnight change in leg fluid volume (LFV) in patients with ESRD. METHODS: We studied 26 patients with ESRD (14 men) on conventional hemodialysis. All subjects underwent polysomnography. LFV was measured by bioelectric impedance at bedtime and repeated in the next morning on awakening. RESULTS: Our cohort's overall apnea hypopnea index was 22.8+/-26.8 episodes/h of sleep. Their overnight change in LFV was -243+/-278 mL. The change in LFV correlated with apnea-hypopnea time (AHT) (P=0.001) and NC (P=0.0016). Other independent factors associated with AHT included age (P=0.005), baseline neck (P=0.0002), sitting time (P=0.008) and male gender. Stepwise multiple regression analysis revealed that age, change in LFV and male gender remained independent related to AHT. CONCLUSIONS: Nocturnal rostral fluid shift is associated with the severity of OSA in ESRD. Prospective evaluation of the effect of reducing fluid overload and severity of OSA in ESRD patients warrants further examination. PMID- 22058176 TI - Association between cold dialysis and cardiovascular survival in hemodialysis patients. AB - BACKGROUND: Higher cardiovascular mortality has been noted in patients with chronic kidney disease (CKD). CKD patients are also known to have impaired energy expenditure but the role of energy expenditure in cardiovascular disease is not yet known. Furthermore, the association between cold dialysis (CD) and clinical outcomes in hemodialysis patients is unclear. METHODS: This was a single-center retrospective cohort study consisting of two groups: a CD group with dialyzate temperature <35.5 degrees C and a standard dialysis (SD) group with dialyzate temperature between 35.5 and 37 degrees C. The end points of the study were overall mortality, cardiac mortality and non-cardiac mortality. The study analyzed the associations between dialyzate temperature and long-term survival in CD and SD groups. Propensity score analysis was used to control for intergroup baseline differences. RESULTS: Baseline characteristics of both groups were similar. Kaplan-Meier analysis showed that CD was significantly associated with a lower risk for overall mortality (P = 0.006) and cardiac mortality (P = 0.023) but not for non-cardiac mortality or infectious mortality. After multivariate Cox regression analysis, adjusting for propensity scores and other possible confounding factors, CD remained a significant beneficial factor for overall mortality (P = 0.030) and cardiac mortality (P = 0.034). CONCLUSION: Our studies show that CD is significantly and independently associated with a lower risk for overall mortality and cardiac mortality. PMID- 22058177 TI - A study of the natural history of diabetic kidney disease (DKD). AB - BACKGROUND: In view of the alarming increase in the number of people with diabetes mellitus (DM), a rising number of patients with diabetic kidney disease (DKD), end-stage renal disease (ESRD) and cardiovascular disease (CVD) is forecasted. It is therefore imperative to re-visit the natural history of DKD and to identify potential risk factors, which may enhance the progression of the disease and its complications. METHODS: The medical records of 270 Type 2 diabetic chronic kidney disease patients followed up at the Sheffield Kidney Institute between 2000 and 2008 were reviewed. Various socio-demographic, clinical and biochemical parameters (baseline and follow-up parameters) were retrospectively collected from the patients' database. Progression of DKD was evaluated by evaluation of the rate of decline of estimated glomerular filtration rate (eGFR) as calculated from the simplified Modification of Diet in Renal Disease formula [progressors: loss of glomerular filtration rate (GFR) >2 mL/min/1.73m(2)/year] as well as by the progression pattern based on the slope of GFR changes. Variables associated with progression in univariate analysis were examined by multivariate analysis to determine the factors independently associated with DKD progression. RESULTS: The majority of the study populations were males (66.7%) and Caucasians (88%). Ninety-four patients (34.8%) had progressive, whereas 176 (65.2%) had non-progressive DKD. The rate of eGFR decline in progressors was -3.57 +/- 1.45 mL/min/1.73m(2)/year compared to -1.31 +/- 0.23 mL/min/1.73m(2)/year in non-progressors. The following parameters discriminated progressors from non-progressors by univariate analysis: baseline blood pressure (BP) parameters, eGFR and proteinuria as well as serum uric acid. We also observed that area under the curve for follow-up systolic blood pressure (SBP), glycosylated haemoglobin (HbA1c) and proteinuria were significantly higher among the progressors (P = 0.043, P = 0.02 and P = 0.001, respectively). Independent determinants of DKD progression in this study in an adjusted logistic regression model were baseline HbA1c [odds ratio (OR), 2.27; 95% confidence interval (CI), 1.14-4.54], baseline SBP (OR, 1.23; 95% CI, 1.06-1.41), baseline proteinuria (OR, 3.24; 95% CI, 2.1-5.38), baseline serum uric acid (OR, 1.16; 95% CI, 1.09-1.39) and vascular co-morbidities (OR, 1.61; 95% CI, 1.02-2.54). Percentage changes in the key parameters (BP, HbA1c and proteinuria) during the first year of the study did not affect the rate of eGFR decline. CONCLUSIONS: Baseline HbA1c, SBP, proteinuria and serum uric acid together with the presence of vascular co-morbidities are strongly and independently associated with faster DKD progression. A further prospective observational study is currently undertaken to evaluate these findings and to determine the predictive value of other biochemical peptides and cellular markers on DKD outcome. PMID- 22058178 TI - Early-onset group B Streptococcal sepsis: new recommendations from the Centres for Disease Control and Prevention. PMID- 22058179 TI - Bifidobacterium septicaemia in an extremely low-birthweight infant under probiotic therapy. PMID- 22058180 TI - Development of microsatellite loci for the endangered species Pityopsis ruthii (Asteraceae). AB - PREMISE OF THE STUDY: Microsatellite loci were developed for the endangered species Pityopsis ruthii and will permit genetic and conservation studies of the species. METHODS AND RESULTS: A microsatellite-enriched library was used to develop 12 polymorphic microsatellite loci for P. ruthii. The loci amplified perfect and imperfect repeats with three to seven alleles per locus. Observed heterozygosity ranged from 0.05 to 0.80 and expected heterozygosity ranged from 0.23 to 0.75. CONCLUSIONS: These microsatellite loci provide a sufficient set of markers for further investigation of population genetics of P. ruthii. PMID- 22058181 TI - Genomics of Compositae weeds: EST libraries, microarrays, and evidence of introgression. AB - PREMISE OF STUDY: Weeds cause considerable environmental and economic damage. However, genomic characterization of weeds has lagged behind that of model plants and crop species. Here we describe the development of genomic tools and resources for 11 weeds from the Compositae family that will serve as a basis for subsequent population and comparative genomic analyses. Because hybridization has been suggested as a stimulus for the evolution of invasiveness, we also analyze these genomic data for evidence of hybridization. METHODS: We generated 22 expressed sequence tag (EST) libraries for the 11 targeted weeds using Sanger, 454, and Illumina sequencing, compared the coverage and quality of sequence assemblies, and developed NimbleGen microarrays for expression analyses in five taxa. When possible, we also compared the distributions of Ks values between orthologs of congeneric taxa to detect and quantify hybridization and introgression. RESULTS: Gene discovery was enhanced by sequencing from multiple tissues, normalization of cDNA libraries, and especially greater sequencing depth. However, assemblies from short sequence reads sometimes failed to resolve close paralogs. Substantial introgression was detected in Centaurea and Helianthus, but not in Ambrosia and Lactuca. CONCLUSIONS: Transcriptome sequencing using next-generation platforms has greatly reduced the cost of genomic studies of nonmodel organisms, and the ESTs and microarrays reported here will accelerate evolutionary and molecular investigations of Compositae weeds. Our study also shows how ortholog comparisons can be used to approximately estimate the genome-wide extent of introgression and to identify genes that have been exchanged between hybridizing taxa. PMID- 22058182 TI - Complex shaped detachable platinum coil system for the treatment of cerebral aneurysms: the Codman Trufill DCS and Trufill DCS Orbit Detachable Coil System COMPLEX Registry final results. AB - OBJECTIVE: To report on an electronic database with longitudinal information on the use of bare platinum coils for the endovascular occlusion of cerebral aneurysms. We report here the final analysis of the data. METHODS: From 1 May 2004 to 10 July 2007, a global registry was conducted at 36 centers in the USA, Europe and Latin America. 303 patients were enrolled, of whom 299 patients were treated with bare detachable platinum coils (mostly Trufill Detachable Coil System (DCS) Orbit coils). Short and long term anatomical and clinical data were collected. Logistic regression analysis was used to examine the association of selected patient characteristics to outcomes of recanalization and retreatment. RESULTS: 313 aneurysms, ruptured and unruptured, were treated in the 299 patients. Follow-up data were available on 185 patients: 150 (81%) had a 3-6 month follow-up, 63 (34%) had a 1 year follow-up and five (3%) had a 2 year follow-up. This paper reviews the status of 185 patients with follow-up data available at this time. Immediately postprocedure, 114 (58%) aneurysms were completely obliterated, 40 (20%) residual neck, 23 (12%) residual aneurysm and 19 (10%) dog ear. Of 174 aneurysms in 167 patients with angiographic follow-up, 137 (79%) remained stable or improved, nine (5%) showed aneurysm regrowth, 26 (15%) showed compaction and two (1%) had migrated. At 3-6 months, 11 of the 174 (6%) aneurysms were re-treated. CONCLUSION: These results confirm previous outcome data of endovascular occlusion of cerebral aneurysms with Trufill DCS Orbit complex shaped detachable platinum coils. Complications related to the device were rare. PMID- 22058184 TI - Health impact assessment of fine particle pollution at the regional level. AB - Since the year 2000, evaluation of the impact of air pollution on people's health has drawn the attention of the general public and has led decision-makers to develop specific health policies. In most of the health impact assessment literature, investigators have reported on long- and short-term effects of air pollution. Here the authors present results of a health impact assessment of short-term effects of particulate matter <=10 MUm in diameter (PM(10)) in the Lombardy region of Italy (2003-2006). The impact was evaluated in terms of numbers of attributable deaths under several counterfactual scenarios of air pollution reduction based on World Health Organization guidelines and European Union limits. The authors found that annual average PM(10) levels exceeding the World Health Organization threshold of 20 MUg/m(3) and the European Union limit of 40 MUg/m(3) were responsible for 302 and 109 attributable deaths per year, corresponding to attributable community rates of 13 and 5 deaths per 100,000 inhabitants per year, respectively. A 20% reduction in existing PM(10) levels could reduce by more than 30% the burden of short-term deaths linked to ambient air pollution. Therefore, policies for air pollution reduction appear to be necessary in order to protect and improve individual and community health. PMID- 22058183 TI - Organ and cell type-specific complementary expression patterns and regulatory neofunctionalization between duplicated genes in Arabidopsis thaliana. AB - Duplicated genes can contribute to the evolution of new functions and they are common in eukaryotic genomes. After duplication, genes can show divergence in their sequence and/or expression patterns. Qualitative complementary expression, or reciprocal expression, is when only one copy is expressed in some organ or tissue types and only the other copy is expressed in others, indicative of regulatory subfunctionalization or neofunctionalization. From analyses of two microarray data sets with 83 different organ types, developmental stages, and cell types in Arabidopsis thaliana, we determined that 30% of whole-genome duplicate pairs and 38% of tandem duplicate pairs show reciprocal expression patterns. We reconstructed the ancestral state of expression patterns to infer that considerably more cases of reciprocal expression resulted from gain of a new expression pattern (regulatory neofunctionalization) than from partitioning of ancestral expression patterns (regulatory subfunctionalization). Pollen was an especially common organ type for expression gain, resulting in contrasting expression of some duplicates in pollen. Many of the gene pairs with reciprocal expression showed asymmetric sequence rate evolution, consistent with neofunctionalization, and the more rapidly evolving copy often showed a more restricted expression pattern. A gene with reciprocal expression in pollen, involved in brassinosteroid signal transduction, has evolved more rapidly than its paralog, and it shows evidence for a new function in pollen. This study indicates the evolutionary importance of reciprocal expression patterns between gene duplicates, showing that they are common, often associated with regulatory neofunctionalization, and may be a factor allowing for retention and divergence of duplicated genes. PMID- 22058185 TI - The marrow of life. PMID- 22058186 TI - Nursing-home-acquired pneumonia in Germany: an 8-year prospective multicentre study. AB - OBJECTIVE: To determine differences in aetiologies, initial antimicrobial treatment choices and outcomes in patients with nursing-home-acquired pneumonia (NHAP) compared with patients with community-acquired pneumonia (CAP), which is a controversial issue. METHODS: Data from the prospective multicentre Competence Network for Community-acquired pneumonia (CAPNETZ) database were analysed for hospitalised patients aged >=65 years with CAP or NHAP. Potential differences in baseline characteristics, comorbidities, physical examination findings, severity at presentation, initial laboratory investigations, blood gases, microbial investigations, aetiologies, antimicrobial treatment and outcomes were determined between the two groups. RESULTS: Patients with NHAP presented with more severe pneumonia as assessed by CRB-65 (confusion, respiratory rate, blood pressure, 65 years and older) score than patients with CAP but received the same frequency of mechanical ventilation and less antimicrobial combination treatment. There were no clinically relevant differences in aetiology, with Streptococcus pneumoniae the most important pathogen in both groups, and potential multidrug-resistant pathogens were very rare (<5%). Only Staphylococcus aureus was more frequent in the NHAP group (n=12, 2.3% of the total population, 3.1% of those with microbial sampling compared with 0.7% and 0.8% in the CAP group, respectively). Short-term and long-term mortality in the NHAP group was higher than in the CAP group for patients aged >=65 years (26.6% vs 7.2% and 43.8% vs 14.6%, respectively). However, there was no association between excess mortality and potential multidrug-resistant pathogens. CONCLUSIONS: Excess mortality in patients with NHAP cannot be attributed to a different microbial pattern but appears to result from increased comorbidities, and consequently, pneumonia is frequently considered and managed as a terminal event. PMID- 22058187 TI - Therapeutic advances in non-small cell lung cancer. AB - Despite decades of research, therapeutic advances in non-small cell lung cancer (NSCLC) have progressed at a painstaking slow rate with few improvements in standard surgical resection for early stage disease and chemotherapy or radiotherapy for patients with advanced disease. In the past 18 months, however, we seemed to have reached an inflexion point: therapeutic advances that are centred on improvements in the understanding of patient selection, surgery that is undertaken through smaller incisions, identification of candidate mutations accompanied by the development of targeted anticancer treatments with a focus on personalised medicine, improvements to radiotherapy technology, emergence of radiofrequency ablation (RFA), and last but by no means least, the recognition of palliative care as a therapeutic modality in its own right. The contributors to this review are a distinguished international panel of experts who highlight recent advances in each of the major disciplines. PMID- 22058188 TI - Fixing cystic fibrosis CFTR with correctors and potentiators. Off to a good start. PMID- 22058189 TI - Smoking accessories for cessation? Mixed messages in Hong Kong. PMID- 22058190 TI - Front-loaded versus weekly counseling for treatment of tobacco addiction. AB - INTRODUCTION: Approximately 60%-70% of cigarette smokers who try to quit relapse by 2 weeks postcessation. We tested the efficacy of a front-loaded (FL) counseling intervention whose goal was to increase the likelihood of successful early abstinence and subsequent long-term abstinence. METHODS: We randomized 278 adult smokers to an FL or weekly behavioral smoking cessation counseling schedule. The total number of sessions across treatment was the same for both groups. However, those assigned to the FL schedule received 6 counseling sessions in the first 2 weeks postcessation, while those in the weekly condition received 2 sessions. Participants in both groups also received standard nicotine patch treatment. RESULTS: At 1 year postcessation, FL participants were significantly less likely to have relapsed when continuous abstinence was used as the definition of abstinence/relapse (11.7% abstinent vs. 6.3%, hazard ratio [HR] = 0.69, p = .007); and there were nonsignificant trends for FL subjects to have better outcomes when abstinence was defined as never smoking for 7 or more consecutive days nor for 7 or more consecutive episodes (18.4% abstinent vs. 14.8%, HR = 0.83, p = .20) and as point prevalence abstinence (15.6% abstinent vs. 12.9%, p = .11). The relationship between FL counseling treatment and continuous abstinence was partially mediated by higher postcessation levels of social support perceived from counseling and greater use of cessation-related coping strategies. CONCLUSIONS: We conclude that FL counseling is a promising treatment model that should be evaluated further, perhaps using modifications of the FL schedule used in this study. PMID- 22058191 TI - Arsenic exposure to killifish during embryogenesis alters muscle development. AB - Epidemiological studies have correlated arsenic exposure in drinking water with adverse developmental outcomes such as stillbirths, spontaneous abortions, neonatal mortality, low birth weight, delays in the use of musculature, and altered locomotor activity. Killifish (Fundulus heteroclitus) were used as a model to help to determine the mechanisms by which arsenic could impact development. Killifish embryos were exposed to three different sodium arsenite concentrations and were collected at 32 h post-fertilization (hpf), 42 hpf, 168 hpf, or < 24 h post-hatch. A killifish oligo microarray was developed and used to examine gene expression changes between control and 25-ppm arsenic-exposed hatchlings. With artificial neural network analysis of the transcriptomic data, accurate prediction of each group (control vs. arsenic-exposed embryos) was obtained using a small subset of only 332 genes. The genes differentially expressed include those involved in cell cycle, development, ubiquitination, and the musculature. Several of the genes involved in cell cycle regulation and muscle formation, such as fetuin B, cyclin D-binding protein 1, and CapZ, were differentially expressed in the embryos in a time- and dose-dependent manner. Examining muscle structure in the hatchlings showed that arsenic exposure during embryogenesis significantly reduces the average muscle fiber size, which is coupled with a significant 2.1- and 1.6-fold upregulation of skeletal myosin light and heavy chains, respectively. These findings collectively indicate that arsenic exposure during embryogenesis can initiate molecular changes that appear to lead to aberrant muscle formation. PMID- 22058192 TI - Psychosocial stress among Danish vicars. AB - BACKGROUND: Burnout and depression are common among clergy members of several religions and denominations. Despite this, no studies have analysed whether differences in psychosocial workloads between vicars and others explain their higher prevalence of stress-related symptoms. AIMS: To test the hypothesis that elements of the job strain model (high work demands, low decision latitude and/or low job support) are mediators of the excess prevalence of stress-related health complaints among vicars compared with other employees in the Church of Denmark. METHODS: Data for this cross-sectional study were collected by means of a self administered questionnaire sent to all employees in 500 Danish parishes (n = 2254). RESULTS: The study response rate was 73%, 35% of respondents were vicars and 43% were female. Compared with other employees, vicars felt quiet and relaxed less often (53 versus 67%), had less time for pleasure and relaxation (28 versus 11%) and felt happy and satisfied (53 versus 67%) less often. Vicars had significantly higher quantitative, cognitive and emotional work demands, lower work support, less influence on whom to collaborate with and less influence on their workload. Psychosocial workloads were more favourable for the vicars who had greater influence on job decisions and on job organization. The higher prevalence of stress-related symptoms among vicars was strongly modified by high work demands, in particular high quantitative demands. CONCLUSIONS: The higher prevalence of stress-related symptoms among vicars could largely be attributed to high-quantitative work demands. PMID- 22058193 TI - Unhealthy and healthy weight control behaviours among bus operators. AB - BACKGROUND: Urban bus operators are an occupational group with high rates of overweight and obesity. Understanding methods bus operators use for weight control may be important; there may be increased risk for these workers to engage in less healthy weight management behaviours due to stressful working conditions. AIMS: To examine the prevalence of unhealthy and healthy weight control behaviours used by bus operators and examine associations between use of unhealthy weight control behaviours and work-related and sociodemographic variables. METHODS: Bus operators from four different transit garages were invited to complete a self-administered survey; height and weight were measured by research staff. Unhealthy and healthy weight control behaviours, work hours, work schedule and social support were measured with self-report items on the employee survey. Logistic regression analysis was conducted to estimate associations. RESULTS: Nearly 60% of bus operators endorsed at least one unhealthy method; over 50% reported skipping meals, 30% fasted and 10% reported taking diet pills in the past year. Bus operator gender, race, body mass index status and hours worked per week showed significant associations with using at least one unhealthy weight control behaviour. CONCLUSIONS: Worksite interventions should emphasize the benefit of healthy eating and physical activity but should also address the use of less healthy methods for weight control for individuals employed in transportation occupations. PMID- 22058194 TI - Hypocellular acute myeloid leukemia in adults: analysis of the clinical outcome of 123 patients. AB - BACKGROUND: The hypocellular variant of acute myeloid leukemia accounts for less than 10% of all cases of adult acute myeloid leukemia. It is defined by having less than 20 percent of cellular bone marrow in a biopsy at presentation. It is unclear in the literature whether the outcome of hypocellular acute myeloid leukemia differs from that of non-hypocellular acute myeloid leukemia. DESIGN AND METHODS: We retrospectively analyzed all the cases reported to be hypocellular acute myeloid leukemia between 2000 and 2009. A second pathology review was conducted and the diagnosis was confirmed in all cases. RESULTS: One hundred twenty-three (9%) patients were identified: patients with hypocellular acute myeloid leukemia were older than those with non-hypocellular acute myeloid leukemia (P=0.009) and more frequently presented with cytopenias (P<0.001). Forty one patients with hypocellular acute myeloid leukemia had an antecedent hematologic disorder and 11 patients had received prior chemo-radiotherapy for non-hematopoietic neoplasms. On multivariate analysis, overall survival, remission duration and event-free survival were comparable to those of other patients with acute myeloid leukemia. CONCLUSIONS: The outcome of hypocellular acute myeloid leukemia does not differ from that of non-hypocellular acute myeloid leukemia. PMID- 22058195 TI - p185(BCR/ABL) has a lower sensitivity than p210(BCR/ABL) to the allosteric inhibitor GNF-2 in Philadelphia chromosome-positive acute lymphatic leukemia. AB - BACKGROUND: The t(9;22) translocation leads to the formation of the chimeric breakpoint cluster region/c-abl oncogene 1 (BCR/ABL) fusion gene on der22, the Philadelphia chromosome. The p185(BCR/ABL) or the p210(BCR/ABL) fusion proteins are encoded as a result of the translocation, depending on whether a "minor" or "major" breakpoint occurs, respectively. Both p185(BCR/ABL) and p210(BCR/ABL) exhibit constitutively activated ABL kinase activity. Through fusion to BCR the ABL kinase in p185(BCR/ABL) and p210(BCR/ABL) "escapes" the auto-inhibition mechanisms of c-ABL, such as allosteric inhibition. A novel class of compounds including GNF-2 restores allosteric inhibition of the kinase activity and the transformation potential of BCR/ABL. Here we investigated whether there are differences between p185(BCR/ABL) and p210(BCR/ABL) regarding their sensitivity towards allosteric inhibition by GNF-2 in models of Philadelphia chromosome positive acute lymphatic leukemia. DESIGN AND METHODS: We investigated the anti proliferative activity of GNF-2 in different Philadelphia chromosome-positive acute lymphatic leukemia models, such as cell lines, patient-derived long-term cultures and factor-dependent lymphatic Ba/F3 cells expressing either p185(BCR/ABL) or p210(BCR/ABL) and their resistance mutants. RESULTS: The inhibitory effects of GNF-2 differed constantly between p185(BCR/ABL) and p210(BCR/ABL) expressing cells. In all three Philadelphia chromosome-positive acute lymphatic leukemia models, p210(BCR/ABL)-transformed cells were more sensitive to GNF-2 than were p185BCR/ABL-positive cells. Similar results were obtained for p185(BCR/ABL) and the p210(BCR/ABL) harboring resistance mutations. CONCLUSIONS: Our data provide the first evidence of a differential response of p185(BCR/ABL)- and p210(BCR/ABL)- transformed cells to allosteric inhibition by GNF-2, which is of importance for the treatment of patients with Philadelphia chromosome-positive acute lymphatic leukemia. PMID- 22058196 TI - Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC. AB - ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyro-sine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAAT-enhancer binding protein alpha(CEBPalpha), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent the same treatment, and evaluate its prognostic impact. Independent factors for survival were age (P=0.0126), ATP-binding cassette transporter activity (P=0.018) and duplications in the fms-like tyrosine kinase 3 (P=0.0273). In the 66 patients without fms-like tyrosine kinase 3 duplication and without nucleophosmin mutation, independent prognostic factors for complete remission achievement and survival were age and ATP-binding cassette transporter activity. In conclusion, ATP-binding cassette transporter activity remains an independent prognostic factor, and could assist treatment decisions in patients with no nucleophosmin mutation and no fms-like tyrosine kinase 3 duplication. PMID- 22058197 TI - Membrane microdomain sphingolipids are required for anti-CD20-induced death of chronic lymphocytic leukemia B cells. AB - BACKGROUND: Chronic lymphocytic leukemia remains incurable, despite the addition of rituximab to chemotherapy as an available means of treatment. The resistance of certain patients to this monoclonal antibody prompted us to set up in vitro studies of another CD20-specific monoclonal antibody, B1 (later termed tositumomab). We hypothesized that the membrane lipid organization of leukemic B cells might be instrumental in the cells' sensitivity to the B1 monoclonal antibody. DESIGN AND METHODS: B lymphocytes from 36 patients with chronic lymphocytic leukemia and 13 patients with non-Hodgkin's lymphoma were investigated for B1-triggered cell death. Membrane components, such as sphingomyelin and ganglioside M1, were investigated by flow cytometry, immunofluorescence and co-immunoprecipitation, together with the Csk-binding protein. RESULTS: Chronic lymphocytic leukemia patients segregated into two groups: B cells from one group were sensitive to B1, whereas those from the second group were not. Further results ascribed the resistance of these latter cases to a defective recruitment of Csk-binding protein, resulting in a lack of sphingomyelin and ganglioside M1 at the outer leaflet of the plasma membrane of their malignant B cells. Sphingolipids were indeed retained in the cytoplasm, because of lowered activity of P-glycoprotein. Supporting this mechanism, rifampicin, an inducer of P-glycoprotein, improved the activity of this transmembrane efflux pump, normalized the quantity of sphingomyelin within the membrane, and thereby restored the efficacy of the B1 monoclonal antibody in the formerly B1-resistant cases of chronic lymphocytic leukemia. CONCLUSIONS: The lipid organization of membranes of B cells from patients with chronic lymphocytic leukemia differs from one patient to another. In practice, given the relevance of the membrane lipid distribution to the efficacy of biotherapies, this observation is of potential importance. PMID- 22058198 TI - Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period. AB - Post-induction aplasia for acute myeloid leukemia/myelodysplastic syndrome is a high-risk period for invasive fungal diseases. The effectiveness of fluconazole, itraconazole solution, voriconazole and posaconazole prophylaxis used consecutively from December 1998 to January 2010 in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing remission-induction chemotherapy was retrospectively evaluated. A total of 216 consecutive patients received 573 prophylaxis courses. Breakthrough-invasive fungal disease incidence in fluconazole, itraconazole, voriconazole, posaconazole recipients was 25%, 16%, 14% and 3%, respectively. Voriconazole/posconazole versus fluconazole/itraconazole combined was associated with significant reductions in breakthrough-invasive fungal disease incidence (20% vs. 8%, P=0.011), premature discontinuations (46% vs. 22% P<0.001) and empiric antifungal treatment (31% vs. 8.5%, P<0.001). Microbiologically confirmed infections were molds. Posaconazole compared to other drugs was associated with fewer courses requiring computed tomography (43% vs. 26%, P<0.001). Adoption of voriconazole/posaconazole has decreased invasive fungal disease incidence, empiric antifungal treatment and for posaconazole, computed-tomography demand, with effectiveness of posaconazole comparable to clinical trial experience. PMID- 22058199 TI - Mimicking the functional hematopoietic stem cell niche in vitro: recapitulation of marrow physiology by hydrogel-based three-dimensional cultures of mesenchymal stromal cells. AB - BACKGROUND: A culture system that closely recapitulates marrow physiology is essential to study the niche-mediated regulation of hematopoietic stem cell fate at a molecular level. We investigated the key features that play a crucial role in the formation of a functional niche in vitro. DESIGN AND METHODS: Hydrogel based cultures of human placenta-derived mesenchymal stromal cells were established to recapitulate the fibrous three-dimensional architecture of the marrow. Plastic-adherent mesenchymal stromal cells were used as controls. Human bone marrow-derived CD34(+) cells were co-cultured with them. The output hematopoietic cells were characterized by various stem cell-specific phenotypic and functional parameters. RESULTS: The hydrogel-cultures harbored a large pool of primitive hematopoietic stem cells with superior phenotypic and functional attributes. Most importantly, like the situation in vivo, a significant fraction of these cells remained quiescent in the face of a robust multi-lineage hematopoiesis. The retention of a high percentage of primitive stem cells by the hydrogel-cultures was attributed to the presence of CXCR4-SDF1alpha axis and integrin beta1-mediated adhesive interactions. The hydrogel-grown mesenchymal stromal cells expressed high levels of several molecules that are known to support the maintenance of hematopoietic stem cells. Yet another physiologically relevant property exhibited by the hydrogel cultures was the formation of hypoxia gradient. Destruction of hypoxia-gradient by incubating these cultures in a hypoxia chamber destroyed their specialized niche properties. CONCLUSIONS: Our data show that hydrogel-based cultures of mesenchymal stromal cells form a functional in vitro niche by mimicking key features of marrow physiology. PMID- 22058200 TI - Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neo angiogenic biomarkers. AB - BACKGROUND: Preclinical studies have highlighted the activity of lenalidomide in mantle cell lymphoma and its anti-proliferative synergy with dexamethasone. DESIGN AND METHODS: In this prospective, multicenter, phase II study, patients with relapsed/refractory mantle cell lymphoma who were not eligible for, or had relapsed after, intensive treatments received lenalidomide 25 mg/day (days 1-21 of each 28-day cycle) and dexamethasone (40 mg/day on days 1, 8, 15, and 22) for up to 12 months. RESULTS: The primary end-points, overall and complete response rates, were achieved by 17 of 33 (52%; 95% confidence interval [CI], 35-68%) and 8 of 33 patients (24%; 95% CI, 13-41%), respectively, by the end of treatment. Fifteen patients (45%) discontinued treatment prematurely, 13 due to lack of response. The median progression-free and overall survival were 12 months (95% CI, 5-19 months) and 20 months (95% CI, 12 months to not estimable), respectively. Treatment resulted in a significant increase in microvessel density (P=0.033) and non-significant increases in macrophage and natural killer cell counts, while serum levels of neoangiogenic factors did not change significantly. Grade 3/4 adverse events were neutropenia (53%), leukopenia (25%), thrombocytopenia (22%), infections (12%), and febrile neutropenia (12%). CONCLUSIONS: These results confirm a favorable safety and activity profile of lenalidomide in relapsed/refractory mantle cell lymphoma. The contribution of dexamethasone in achieving these results is unclear because of its possible detrimental effect on the immune activation generated by lenalidomide and a higher risk of developing infectious complications. (clinicaltrials.gov identifier: NCT00786851). PMID- 22058201 TI - Characterization of a pediatric T-cell acute lymphoblastic leukemia patient with simultaneous LYL1 and LMO2 rearrangements. AB - Translocation of the LYL1 oncogene are rare in T-cell acute lymphoblastic leukemia, whereas the homologous TAL1 gene is rearranged in approximately 20% of patients. Previous gene-expression studies have identified an immature T-cell acute lymphoblastic leukemia subgroup with high LYL1 expression in the absence of chromosomal aberrations. Molecular characterization of a t(7;19)(q34;p13) in a pediatric T-cell acute lymphoblastic leukemia patient led to the identification of a translocation between the TRB@ and LYL1 loci. Similar to incidental T-cell acute lymphoblastic leukemia cases with synergistic, double translocations affecting TAL1/2 and LMO1/2 oncogenes, this LYL1-translocated patient also had an LMO2 rearrangement pointing to oncogenic cooperation between LYL1 and LMO2. In hierarchical cluster analyses based on gene-expression data, this sample consistently clustered along with cases having TAL1 or LMO2 rearrangements. Therefore, LYL1-rearranged cases are not necessarily associated with immature T cell development, despite high LYL1 levels, but elicit a TALLMO expression signature. PMID- 22058202 TI - Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach. AB - BACKGROUND: Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients' risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. DESIGN AND METHODS: This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. RESULTS: Eighty five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. CONCLUSIONS: Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell transplant, the approach is useful for identifying patients who are not likely to develop invasive fungal infection and do not, therefore, require antifungal therapy. The effectiveness of the strategy is similar to that of universal empirical antifungal therapy reported in controlled trials. PMID- 22058203 TI - In situ mantle cell lymphoma: clinical implications of an incidental finding with indolent clinical behavior. AB - BACKGROUND: Cyclin D1-positive B cells are occasionally found in the mantle zones of reactive lymphoid follicles, a condition that has been called "in situ mantle cell lymphoma". The clinical significance of this lesion remains uncertain. DESIGN AND METHODS: The clinical and pathological characteristics, including SOX11 expression, of 23 cases initially diagnosed as in situ mantle cell lymphoma were studied. RESULTS: Seventeen of the 23 cases fulfilled the criteria for in situ mantle cell lymphoma. In most cases, the lesions were incidental findings in reactive lymph nodes. The t(11;14) was detected in all eight cases examined. SOX11 was positive in seven of 16 cases (44%). Five cases were associated with other small B-cell lymphomas. In two cases, both SOX11-positive, the in situ mantle cell lymphoma lesions were discovered after the diagnosis of overt lymphoma; one 4 years earlier, and one 3 years later. Twelve of the remaining 15 patients had a follow-up of at least 1 year (median 2 years; range, 1-19.5), of whom 11 showed no evidence of progression, including seven who were not treated. Only one of 12 patients with an in situ mantle cell lymphoma lesion and no diagnosis of mantle cell lymphoma at the time developed an overt lymphoma, 4 years later; this case was also SOX11-positive. The six remaining cases were diagnosed as mantle cell lymphoma with a mantle zone pattern. Five were SOX11 positive and four of them were associated with lymphoma without a mantle zone pattern. CONCLUSIONS: In situ mantle cell lymphoma lesions are usually an incidental finding with a very indolent behavior. These cases must be distinguished from mantle cell lymphoma with a mantle zone pattern and overt mantle cell lymphoma because they may not require therapeutic intervention. PMID- 22058204 TI - MicroRNAs are shaping the hematopoietic landscape. AB - Hematopoiesis is regulated by microRNAs (miRNAs). These small regulatory RNAs are master regulators of developmental processes that modulate expression of several target genes post-transcriptionally. Various miRNAs are up-regulated at specific stages during hematopoietic development and the functional relevance of miRNAs has been proven at many different stages of lineage specification. Knockout of specific miRNAs can produce dramatic phenotypes leading to severe hematopoietic defects. Furthermore, several studies demonstrated that specific miRNAs are differentially expressed in hematopoietic stem cells. However, the emerging picture is extremely complex due to differences between species, cell type dependent variation in miRNA expression and differential expression of diverse target genes that are involved in various regulatory networks. There is also evidence that miRNAs play a role in cellular aging or in the inter-cellular crosstalk between hematopoietic cells and their microenvironment. The field is rapidly evolving due to new profiling tools and deep sequencing technology. The expression profiles of miRNAs are of diagnostic relevance for classification of different diseases. Recent reports on the generation of induced pluripotent stem cells with miRNAs have fuelled the hope that specific miRNAs and culture conditions facilitate directed differentiation or culture expansion of the hematopoietic stem cell pool. This review summarizes our current knowledge about miRNA expression in hematopoietic stem and progenitor cells, and their role in the hematopoietic stem cell niche. PMID- 22058205 TI - Oxygen tension plays a critical role in the hematopoietic microenvironment in vitro. AB - BACKGROUND: In the bone marrow mesenchymal stromal cells and osteoblasts form functional niches for hematopoietic stem and progenitor cells. This microenvironment can be partially mimicked using in vitro co-culture systems. In this study, we examined the oxygen tension in three distinct compartments in a co culture system of purified CD34(+) cells and mesenchymal stromal cells with regard to different spatial localizations. DESIGN AND METHODS: Hypoxic cells in the co-culture were visualized by pimonidazole staining. Hematopoietic cell distribution, and functional and phenotypic characteristics were analyzed by flow cytometry. The secretion of vascular endothelial growth factor and stromal derived factor-1 by mesenchymal stromal cells in low oxygen co-cultures was determined by an enzyme-linked immunosorbent assay. The effect of co-culture medium on the hematopoietic cell migration potential was tested in a transwell assay. RESULTS: In co-cultures under atmospheric oxygen tension, regions of low oxygen tension could be detected beneath the feeder layer in which a reservoir of phenotypically more primitive hematopoietic cells is located in vitro. In low oxygen co-culture, the adhesion of hematopoietic cells to the feeder layer was decreased, whereas hematopoietic cell transmigration beneath mesenchymal stromal cells was favored. Increased vascular endothelial growth factor-A secretion by mesenchymal stromal cells under low oxygen conditions, which increased the permeability of the monolayer, was responsible for this effect. Furthermore, vascular endothelial growth factor-A expression in low oxygen mesenchymal stromal cells was induced via hypoxia-inducible factor signaling. However, stromal cell derived factor-1 secretion by mesenchymal stromal cells was down-regulated under low oxygen conditions in a hypoxia-inducible factor-independent manner. CONCLUSIONS: We demonstrate for the first time that differences in oxygen tension cause selective modification of hematopoietic cell and mesenchymal stromal cell interactions in a co-culture system, thus confirming that oxygen tension plays a critical role in the interaction between hematopoietic cells and the niche environment. PMID- 22058206 TI - Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: a Chronic Graft-versus-Host Disease Consortium study. AB - BACKGROUND: The National Institutes of Health Consensus Conference proposed the term "overlap" graft-versus-host disease to describe the situation when both acute and chronic graft-versus-host disease are present. DESIGN AND METHODS: We examined whether the overlap subtype of graft-versus-host disease was associated with a different prognosis, functional limitations, or patient-reported outcomes compared to "classic" chronic graft-versus-host disease without any acute features. RESULTS: Prospective data were collected from 427 patients from nine centers. Patients were classified as having overlap (n=352) or classic chronic (n=75) graft-versus-host disease based on reported organ involvement. Overlap cases had a significantly shorter median time from transplantation to cohort enrollment (P=0.01), were more likely to be incident cases (P<0.001), and had a lower platelet count at onset of the graft-versus-host disease (P<0.001). Patients with overlap graft-versus-host disease had significantly greater functional impairment measured by a 2-minute walk test, higher symptom burden and lower Human Activity Profile scores. Quality of life was similar, except patients with overlap graft-versus-host disease had worse social functioning, assessed by the Short Form-36. Multivariable analysis utilizing time-varying covariates demonstrated that the overlap subtype of graft-versus-host disease was associated with worse overall survival (HR 2.1, 95% CI 1.1-4.7; P=0.03) and higher non relapse mortality (HR 2.8, 95% CI 1.2-8.3; P=0.02) than classic chronic graft versus-host disease. CONCLUSIONS: These findings suggest that the presence of acute features in patients with chronic graft-versus-host disease is a marker of adverse prognosis, greater functional impairment, and higher symptom burden. PMID- 22058207 TI - Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value. AB - Somatic mutations in the additional sex comb-like 1 (ASXL1) gene have been described in various types of myeloid malignancies, including acute myeloid leukemia. Analysis of novel markers, such as ASXL1 mutations, in independent clinical trials is indispensable before considering them for clinical decision making. We analyzed 882 well-characterized acute myeloid leukemia cases to determine the prevalence and prognostic impact of ASXL1 exon12 mutations. Truncating ASXL1 mutations were present in 46 cases (5.3%). ASXL1 mutations were inversely associated with FLT3 internal tandem duplications and mutually exclusive with NPM1 mutations. ASXL1 mutations were an unfavorable prognostic factor as regards survival (median overall survival 15.9 months vs. 22.3 months; P=0.019), with a significantly lower complete response rate (61% vs. 79.6%; P=0.004). In multivariate analyses, ASXL1 mutations were independently associated with inferior poor overall survival (HR 1.52, P=0.032). In conclusion, ASXL1 mutations are common mutations in acute myeloid leukemia and indicate a poor therapy outcome. PMID- 22058208 TI - Epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia modulates proliferation, cell survival and chemosensitivity. AB - BACKGROUND: Altered regulation of many transcription factors has been shown to be important in the development of leukemia. TWIST2 modulates the activity of a number of important transcription factors and is known to be a regulator of hematopoietic differentiation. Here, we investigated the significance of epigenetic regulation of TWIST2 in the control of cell growth and survival and in response to cytotoxic agents in acute lymphoblastic leukemia. DESIGN AND METHODS: TWIST2 promoter methylation status was assessed quantitatively, by combined bisulfite and restriction analysis (COBRA) and pyrosequencing assays, in multiple types of leukemia and TWIST2 expression was determined by quantitative reverse transcriptase polymerase chain reaction analysis. The functional role of TWIST2 in cell proliferation, survival and response to chemotherapy was assessed in transient and stable expression systems. RESULTS: We found that TWIST2 was inactivated in more than 50% of cases of childhood and adult acute lymphoblastic leukemia through promoter hypermethylation and that this epigenetic regulation was especially prevalent in RUNX1-ETV6-driven cases. Re-expression of TWIST2 in cell lines resulted in a dramatic reduction in cell growth and induction of apoptosis in the Reh cell line. Furthermore, re-expression of TWIST2 resulted in increased sensitivity to the chemotherapeutic agents etoposide, daunorubicin and dexamethasone and TWIST2 hypermethylation was almost invariably found in relapsed adult acute lymphoblastic leukemia (91% of samples hypermethylated). CONCLUSIONS: This study suggests a dual role for epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia, initially through altering cell growth and survival properties and subsequently by increasing resistance to chemotherapy. PMID- 22058210 TI - t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34. AB - Genetic events underlying pathogenesis of nodal and extranodal marginal zone lymphoma are not completely understood. We report here a novel t(X;14)(p11.4;q32.33) identified in 4 lymphoma cases: 2 with a mucosa-associated lymphoid tissue lymphoma, one with a nodal marginal zone lymphoma and one with gastric diffuse large B-cell lymphoma. In all cases, lymphoma evolved from a previous auto-immune disorder. Fluorescence in situ hybridization and molecular studies showed that t(X;14), which is mediated by immunoglobulin heavy chain locus, targets the GPR34 gene at Xp11.4. Upregulation of GPR34 mRNA and aberrant expression of GPR34 protein has been demonstrated in 3 presented cases by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. GPR34 belongs to the largest family of cell surface molecules involved in signal transmission that play important roles in many physiological and pathological processes, including tumorigenesis. Although functional consequences of t(X;14) have not been identified, our studies suggest that up regulated GPR34 activate neither nuclear factor-kappaB nor ELK-related tyrosine kinase. PMID- 22058209 TI - Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results. AB - BACKGROUND: Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. DESIGN AND METHODS: Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. RESULTS: The post-induction overall response rate (>= partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44-2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. CONCLUSIONS: The cyclophosphamide thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111). PMID- 22058211 TI - POEMS syndrome with severe neurological damage clinically recovered with lenalidomide. PMID- 22058212 TI - Functional analysis of the NUP98-CCDC28A fusion protein. AB - BACKGROUND: The nucleoporin gene NUP98 is rearranged in more than 27 chromosomal abnormalities observed in childhood and adult, de novo and therapy-related acute leukemias of myeloid and T-lymphoid origins, resulting in the creation of fusion genes and the expression of chimeric proteins. We report here the functional analysis of the NUP98-coiled-coil domain-containing protein 28A (NUP98-CCDC28A) fusion protein, expressed as the consequence of a recurrent t(6;11)(q24.1;p15.5) translocation. DESIGN AND METHODS: To gain insight into the function of the native CCDC28A gene, we collected information on any differential expression of CCDC28A among normal hematologic cell types and within subgroups of acute leukemia. To assess the in vivo effects of the NUP98-CCDC28A fusion, NUP98 CCDC28A or full length CCDC28A were retrovirally transduced into primary murine bone marrow cells and transduced cells were next transplanted into sub-lethally irradiated recipient mice. RESULTS: Our in silico analyses supported a contribution of CCDC28A to discrete stages of murine hematopoietic development. They also suggested selective enrichment of CCDC28A in the French-American British M6 class of human acute leukemia. Primary murine hematopoietic progenitor cells transduced with NUP98-CCDC28A generated a fully penetrant and transplantable myeloproliferative neoplasm-like myeloid leukemia and induced selective expansion of granulocyte/macrophage progenitors in the bone marrow of transplanted recipients, showing that NUP98-CCDC28A promotes the proliferative capacity and self-renewal potential of myeloid progenitors. In addition, the transformation mediated by NUP98-CCDC28A was not associated with deregulation of the Hoxa-Meis1 pathway, a feature shared by a diverse set of NUP98 fusions. CONCLUSIONS: Our results demonstrate that the recurrent NUP98-CCDC28A is an oncogene that induces a rapid and transplantable myeloid neoplasm in recipient mice. They also provide additional evidence for an alternative leukemogenic mechanism for NUP98 oncogenes. PMID- 22058213 TI - Diagnostic power of laboratory tests for hereditary spherocytosis: a comparison study in 150 patients grouped according to molecular and clinical characteristics. AB - BACKGROUND: The laboratory diagnosis of hereditary spherocytosis commonly relies on NaCl-based or glycerol-based red cell osmotic fragility tests; more recently, an assay directly targeting the hereditary spherocytosis molecular defect (eosin 5'-maleimide-binding test) has been proposed. None of the available tests identifies all cases of hereditary spherocytosis. DESIGN AND METHODS: We compared the performances of the eosin-5'-maleimide-binding test, NaCl-osmotic fragility studies on fresh and incubated blood, the glycerol lysis test, the acidified glycerol lysis test, and the Pink test on a series of 150 patients with hereditary spherocytosis grouped according to clinical phenotype and the defective protein, with the final aim of finding the combination of tests associated with the highest diagnostic power, even in the mildest cases of hereditary spherocytosis. RESULTS: The eosin-5'-maleimide-binding test had a sensitivity of 93% and a specificity of 98% for detecting hereditary spherocytosis: the sensitivity was independent of the type and amount of molecular defect and of the clinical phenotype. The acidified glycerol lysis test and Pink test showed comparable sensitivity (95% and 91%). The sensitivity of NaCl osmotic fragility tests, commonly considered the gold standard for the diagnosis of hereditary spherocytosis, was 68% on fresh blood and 81% on incubated blood, and further decreased in compensated cases (53% and 64%, respectively). The combination of the eosin-5'-maleimide-binding test and acidified glycerol lysis test enabled all patients with hereditary spherocytosis to be identified. The eosin-5'-maleimide-binding test showed the greatest disease specificity. CONCLUSIONS: Each type of test fails to diagnose some cases of hereditary spherocytosis. The association of an eosin-5'-maleimide-binding test and an acidified glycerol lysis test enabled identification of all patients with hereditary spherocytosis in this series and, therefore, represents a currently effective diagnostic strategy for hereditary spherocytosis including mild/compensated cases. PMID- 22058214 TI - Plasma thymus and activation-regulated chemokine as an early response marker in classical Hodgkin's lymphoma. AB - BACKGROUND: Plasma thymus and activation-regulated chemokine is a potential biomarker for classical Hodgkin's lymphoma. To define its value as a marker to monitor treatment response, we correlated serial plasma thymus and activation regulated chemokine levels with clinical response in newly diagnosed and relapsed classical Hodgkin's lymphoma patients. DESIGN AND METHODS: Plasma was collected from 60 (39 early stage and 21 advanced stage) newly diagnosed classical Hodgkin's lymphoma patients before, during, and after treatment, and from 12 relapsed patients before and after treatment. Plasma thymus and activation regulated chemokine levels were determined by enzyme-linked immunosorbent assay and were related to pre-treatment metabolic tumor volume, as measured by quantification of 2-[18F]fluoro-2-deoxyglucose positron emission tomography images, and to treatment response. RESULTS: Baseline plasma thymus and activation regulated chemokine levels correlated with stage of disease and bulky disease, and more closely with metabolic tumor volume. Response to treatment was observed among 38 of 39 early stage and 19 of 21 advanced stage patients. Reduction in plasma thymus and activation-regulated chemokine to normal range levels could be observed as early as after one cycle of chemotherapy in all responsive patients, while plasma levels remained elevated during and after treatment in the 3 non responsive patients. Plasma thymus and activation-regulated chemokine was elevated in all 12 relapsed patients at time of relapse and remained elevated after salvage treatment in the 4 non-responsive patients. CONCLUSIONS: Baseline plasma thymus and activation-regulated chemokine levels correlate with classical Hodgkin's lymphoma tumor burden and serial levels correlate with response to treatment in patients with classical Hodgkin's lymphoma. PMID- 22058215 TI - European Bone Marrow Working Group trial on reproducibility of World Health Organization criteria to discriminate essential thrombocythemia from prefibrotic primary myelofibrosis. AB - BACKGROUND: The World Health Organization classification of myeloproliferative neoplasms discriminates between essential thrombocythemia and the prefibrotic phase of primary myelofibrosis. This discrimination is clinically relevant because essential thrombocythemia is associated with a favorable prognosis whereas patients with primary myelofibrosis have a higher risk of progression to myelofibrosis or blast crisis. DESIGN AND METHODS: To assess the reproducibility of the classification, six hematopathologists from five European countries re classified 102 non-fibrotic bone marrow trephines, obtained because of sustained thrombocytosis. RESULTS: Consensus on histological classification defined as at least four identical diagnoses occurred for 63% of the samples. Inter-observer agreement showed low to moderate kappa values (0.28 to 0.57, average 0.41). The percentage of unclassifiable myeloproliferative neoplasms rose from 2% to 23% when minor criteria for primary myelofibrosis were taken into account. In contrast, the frequency of primary myelofibrosis dropped from 23% to 7%, indicating that the majority of patients with a histological diagnosis of primary myelofibrosis did not fulfill the complete criteria for this disease. Thus, over 50% of cases in this series either could not be reproducibly classified or fell into the category of unclassifiable myeloproliferative neoplasms. CONCLUSIONS: World Health Organization criteria for discrimination of essential thrombocythemia from prefibrotic primary myelofibrosis are poorly to only moderately reproducible and lead to a higher proportion of non-classifiable myeloproliferative neoplasms than histology alone. PMID- 22058216 TI - A risk of essential thrombocythemia in carriers of constitutional CHEK2 gene mutations. AB - Germline mutations of the CHEK2 gene have been reported in some myeloid and lymphoid malignancies, but their impact on development of essential thrombocythemia has not been studied. In 16 out of 106 (15.1%) consecutive patients, newly diagnosed with essential thrombocythemia, we found one of four analyzed CHEK2 mutations: I157T, 1100delC, IVS2+1G>A or del5395. They were associated with the increased risk of disease (OR=3.8; P=0.002). The median age at ET diagnosis among CHEK2+/JAK2V617F+ patients was seven years lower than that among CHEK2-/JAK2V617F+ (52 vs. 59 years; P=0.04), whereas there was no difference in the medians of hematologic parameters between these groups. The results obtained suggest that CHEK2 mutations could potentially contribute to the susceptibility to essential thrombocythemia. The germline inactivation of CHEK2, as it seems, has no direct impact on the development of disease, but it could cause disruption of cell cycle checkpoints and initiate or support the cancerogenic process of essential thrombocythemia at a younger age. PMID- 22058217 TI - CD20 expression has no prognostic role in Philadelphia-negative B-precursor acute lymphoblastic leukemia: new insights from the molecular study of minimal residual disease. AB - The prognostic significance of CD20 expression in acute lymphoblastic leukemia has been investigated in children and adults but is still a subject of debate. The aim of our study was to correlate CD20 expression with clinical-biological characteristics and outcome in 172 Philadelphia chromosome negative patients prospectively treated in a multicenter trial introducing the molecular evaluation of minimal residual disease for therapeutic purposes. We considered 20% as the threshold for CD20 positivity. Complete remission rate, minimal residual disease negativity rate at weeks 10, 16 and 22, and disease-free and overall survival were similar among CD20-positive and -negative patients, even considering minimal residual disease results and related therapeutic choices. Our study failed to demonstrate any prognostic significance for CD20 expression in Philadelphia chromosome negative acute lymphoblastic leukemia. This conclusion is supported for the first time by a comparable minimal residual disease response rate among CD20-positive and -negative and positive patients. PMID- 22058218 TI - Younger donor's age and upfront tandem are two independent prognostic factors for survival in multiple myeloma patients treated by tandem autologous-allogeneic stem cell transplantation: a retrospective study from the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC). AB - BACKGROUND: How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC). DESIGN AND METHODS: This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure. RESULTS: Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2-132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39-57 %) and 27% (95% CI 19-36), respectively. Eighteen patients (12%) experienced grade III-IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant related mortality rate at 1 year was 15% (95% CI 10-22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor's age <= 50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor's age <= 50 years and full chimerism were independent prognostic factors for better outcome. CONCLUSIONS: We confirmed the feasibility of tandem autologour-allogeneic transplantation in heavily treated patients with multiple myeloma. We identified younger donor's age and upfront tandem transplantation as two independent prognostic factors for survival which could be further explored in prospective studies. PMID- 22058219 TI - A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy. AB - BACKGROUND: The treatment of acute myeloid leukemia of older, medically non-fit patients still poses a highly unmet clinical need, and only few large, prospective studies have been performed in this setting. Given the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine (decitabine) in myelodysplastic syndromes and acute myeloid leukemia with 20-30% bone marrow blasts, we investigated whether this drug is also active in patients with more than 30% blasts. DESIGN AND METHODS: To evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy, 227 patients (median age, 72 years), many with comorbidities, adverse cytogenetics and/or preceding myelodysplastic syndrome were treated with this hypomethylating agent. During the initial decitabine treatment (135 mg/m(2) total dose infused intravenously over 72 hours every 6 weeks), a median of two cycles was administered (range, 1-4). All-trans retinoic acid was administered to 100 patients during course 2. Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses (range, 1-19) with a lower dose of decitabine (20 mg/m(2)) infused over 1 hour on 3 consecutive days every 4-6 weeks. RESULTS: The complete and partial remission rate was 26%, 95% CI (20%, 32%), and an antileukemic effect was noted in 26% of patients. Response rates did not differ between patients with or without adverse cytogenetics; patients with monosomal karyotypes also responded. The median overall survival from the start of decitabine treatment was 5.5 months (range, 0-57.5+) and the 1-year survival rate was 28%, 95%CI (22%,34%). Toxicities were predominantly hematologic. CONCLUSIONS: Decitabine is well tolerated by older, medically non-fit patients with acute myeloid leukemia; myelosuppression is the major toxicity. The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome. Because of these encouraging results, randomized studies evaluating single-agent decitabine versus conventional treatment are warranted. The study is registered with the German Clinical Trials Registry, number DRKS00000069. PMID- 22058220 TI - Telomere length is associated with disease severity and declines with age in dyskeratosis congenita. AB - BACKGROUND: Dyskeratosis congenita is a cancer-prone bone marrow failure syndrome caused by aberrations in telomere biology. DESIGN AND METHODS: We studied 65 patients with dyskeratosis congenita and 127 unaffected relatives. Telomere length was measured by automated multicolor flow fluorescence in situ hybridization in peripheral blood leukocyte subsets. We age-adjusted telomere length using Z-scores (standard deviations from the mean for age). RESULTS: We confirmed that telomere lengths below the first percentile for age are very sensitive and specific for the diagnosis of dyskeratosis congenita. We provide evidence that lymphocytes alone and not granulocytes may suffice for clinical screening, while lymphocyte subsets may be required for challenging cases, including identification of silent carriers. We show for the first time using flow fluorescence in situ hybridization that the shortest telomeres are associated with severe variants (Hoyeraal-Hreidarsson and Revesz syndromes), mutations in DKC1, TINF2, or unknown genes, and moderate or severe aplastic anemia. In the first longitudinal follow up of dyskeratosis congenita patients, we demonstrate that telomere lengths decline with age, in contrast to the apparent stable telomere length observed in cross-sectional data. CONCLUSIONS: Telomere length by flow fluorescence in situ hybridization is an important diagnostic test for dyskeratosis congenita; age-adjusted values provide a quantitative measure of disease severity (clinical subset, mutated gene, and degree of bone marrow failure). Patients with dyskeratosis congenita have accelerated telomere shortening. This study is registered at www.clinicaltrials.gov (identifier: NCT00027274). PMID- 22058221 TI - AMD3100 disrupts the cross-talk between chronic lymphocytic leukemia cells and a mesenchymal stromal or nurse-like cell-based microenvironment: pre-clinical evidence for its association with chronic lymphocytic leukemia treatments. AB - BACKGROUND: Interactions with the microenvironment, such as bone marrow mesenchymal stromal cells and nurse-like cells, protect chronic lymphocytic leukemia cells from spontaneous and drug-induced apoptosis. This protection is partially mediated by the chemokine SDF-1alpha (CXCL12) and its receptor CXCR4 (CD184) present on the chronic lymphocytic leukemia cell surface. DESIGN AND METHODS: Here, we investigated the ability of AMD3100, a CXCR4 antagonist, to sensitize chronic lymphocytic leukemia cells to chemotherapy in a chronic lymphocytic leukemia/mesenchymal stromal cell based or nurse-like cell based microenvironment co-culture model. RESULTS: AMD3100 decreased CXCR4 expression signal (n=15, P=0.0078) and inhibited actin polymerization/migration in response to SDF-1alpha (n=8, P<0.01) and pseudoemperipolesis (n=10, P=0.0010), suggesting that AMD3100 interferes with chronic lymphocytic leukemia cell trafficking. AMD3100 did not have a direct effect on apoptosis when chronic lymphocytic leukemia cells were cultured alone (n=10, P=0.8812). However, when they were cultured with SDF-1alpha, mesenchymal stromal cells or nurse-like cells (protecting them from apoptosis, P<0.001), chronic lymphocytic leukemia cell pre treatment with AMD3100 significantly inhibited these protective effects (n=8, P<0.01) and decreased the expression of the anti-apoptotic proteins MCL-1 and FLIP. Furthermore, combining AMD3100 with various drugs (fludarabine, cladribine, valproic acid, bortezomib, flavopiridol, methylprednisolone) in our mesenchymal stromal cell co-culture model enhanced drug-induced apoptosis (n=8, P<0.05) indicating that AMD3100 could mobilize chronic lymphocytic leukemia cells away from their protective microenvironment, making them more accessible to conventional therapies. CONCLUSIONS: Taken together, these data demonstrate that interfering with the SDF-1alpha/CXCR4 axis by using AMD3100 inhibited chronic lymphocytic leukemia cell trafficking and microenvironment-mediated protective effects. Combining AMD3100 with other drugs may, therefore, represent a promising therapeutic approach to kill chronic lymphocytic leukemia cells. PMID- 22058222 TI - Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance. AB - BACKGROUND: The levels and clinical relevance of Th17 cells and other interleukin 17-producing cells have not been analyzed in chronic lymphocytic leukemia. The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome. DESIGN AND METHODS: Intracellular interleukin-17A was assessed in blood and splenic mononuclear cells from patients with chronic lymphocytic leukemia and healthy subjects using flow cytometry. Interleukin-17A producing cells were analyzed in formalin-fixed, paraffin-embedded spleen and lymph node sections using immunohistochemistry and immunofluorescence. RESULTS: The absolute numbers of Th17 cells in peripheral blood mononuclear cells and the percentages of Th17 cells in spleen cell suspensions were higher in patients with chronic lymphocytic leukemia than in healthy subjects; in six out of eight paired chronic lymphocytic leukemia blood and spleen sample comparisons, Th17 cells were enriched in spleen suspensions. Circulating Th17 levels correlated with better prognostic markers and longer overall survival of the patients. Two "non-Th17" interleukin-17-expressing cells were identified in chronic lymphocytic leukemia spleens: proliferating cells of the granulocytic lineage and mature mast cells. Granulocytes and mast cells in normal spleens did not express interleukin-17. Conversely, both chronic lymphocytic leukemia and healthy lymph nodes contained similar numbers of interleukin-17+ mast cells as well as Th17 cells. CONCLUSIONS: Th17 cells are elevated in chronic lymphocytic leukemia patients with better prognostic markers and correlate with longer survival. Furthermore, non-Th17 interleukin-17A-expressing cells exist in chronic lymphocytic leukemia spleens as maturing granulocytes and mature mast cells, suggesting that the microenvironmental milieu in leukemic spleens promotes the recruitment and/or expansion of Th17 and other IL-17-expressing cells. The pathophysiology of Th17 and non-Th17-interleukin-producing cells in chronic lymphocytic leukemia and their distributions and roles in this disease merit further study. PMID- 22058223 TI - Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease. AB - BACKGROUND: Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease. DESIGN AND METHODS: In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (>= 25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria. RESULTS: There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively). CONCLUSIONS: Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease. PMID- 22058224 TI - Low platelet counts after induction therapy for childhood acute lymphoblastic leukemia are strongly associated with poor early response to treatment as measured by minimal residual disease and are prognostic for treatment outcome. AB - BACKGROUND: Numerous reports have been published on the association between kinetics of leukemic cells during early treatment of childhood acute lymphoblastic leukemia and therapeutic outcome. In contrast, little is known about the prognostic relevance of normal blood counts in this setting. DESIGN AND METHODS: Normal hematopoiesis during and after induction treatment (days 8, 15 and 33) was correlated with therapeutic outcome in a cohort of 256 children with acute lymphoblastic leukemia treated in one of three consecutive ALL-BFM trials at a single institute. Replication analysis of positive findings was performed in an independent cohort of 475 patients from the ALL-BFM 2000 multicenter trial. RESULTS: A platelet count in the first quartile on treatment day 33 and a neutrophil count above the median on day 8 were significantly associated with treatment outcome, conferring multivariate risk ratios for an event of 3.27 (95% confidence interval 1.60-6.69) and 2.26 (95% confidence interval 1.23-4.29), respectively. Replication analysis confirmed the prognostic effect of platelet count on treatment day 33 and demonstrated a strong association with minimal residual disease-based risk group distribution (P<0.00001). CONCLUSIONS: Platelet counts after induction treatment may improve treatment stratification for patients with childhood acute lymphoblastic leukemia and be of particular interest in non-minimal residual disease-based trials. (ALL-BFM 2000 is registered at: ClinicalTrials.gov: NCT00430118. National Cancer Institute: Protocol ID 68529). PMID- 22058225 TI - Thousands of cis-regulatory sequence combinations are shared by Arabidopsis and poplar. AB - The identification of cis-regulatory modules (CRMs) can greatly advance our understanding of gene regulatory mechanisms. Despite the existence of binding sites of more than three transcription factors (TFs) in a CRM, studies in plants often consider only the cooccurrence of binding sites of one or two TFs. In addition, CRM studies in plants are limited to combinations of only a few families of TFs. It is thus not clear how widespread plant TFs work together, which TFs work together to regulate plant genes, and how the combinations of these TFs are shared by different plants. To fill these gaps, we applied a frequent pattern-mining-based approach to identify frequently used cis-regulatory sequence combinations in the promoter sequences of two plant species, Arabidopsis (Arabidopsis thaliana) and poplar (Populus trichocarpa). A cis-regulatory sequence here corresponds to a DNA motif bound by a TF. We identified 18,638 combinations composed of two to six cis-regulatory sequences that are shared by the two plant species. In addition, with known cis-regulatory sequence combinations, gene function annotation, gene expression data, and known functional gene sets, we showed that the functionality of at least 96.8% and 65.2% of these shared combinations in Arabidopsis are partially supported, under a false discovery rate of 0.1 and 0.05, respectively. Finally, we discovered that 796 of the 18,638 combinations might relate to functions that are important in bioenergy research. Our work will facilitate the study of gene transcriptional regulation in plants. PMID- 22058226 TI - Nicotinamide mononucleotide adenylyl transferase 1 protects against acute neurodegeneration in developing CNS by inhibiting excitotoxic-necrotic cell death. AB - Hypoxic-ischemic (H-I) injury to the developing brain is a significant cause of morbidity and mortality in humans. Other than hypothermia, there is no effective treatment to prevent or lessen the consequences of neonatal H-I. Increased expression of the NAD synthesizing enzyme nicotinamide mononucleotide adenylyl transferase 1 (Nmnat1) has been shown to be neuroprotective against axonal injury in the peripheral nervous system. To investigate the neuroprotective role of Nmnat1 against acute neurodegeneration in the developing CNS, we exposed wild type mice and mice overexpressing Nmnat1 in the cytoplasm (cytNmnat1-Tg mice) to a well-characterized model of neonatal H-I brain injury. As early as 6 h after H I, cytNmnat1-Tg mice had strikingly less injury detected by MRI. CytNmnat1-Tg mice had markedly less injury in hippocampus, cortex, and striatum than wild-type mice as assessed by loss of tissue volume 7 d days after H-I. The dramatic protection mediated by cytNmnat1 is not mediated through modulating caspase3 dependent cell death in cytNmnat1-Tg brains. CytNmnat1 protected neuronal cell bodies and processes against NMDA-induced excitotoxicity, whereas caspase inhibition or B-cell lymphoma-extra large (Bcl-XL) protein overexpression had no protective effects in cultured cortical neurons. These results suggest that cytNmnat1 protects against neonatal HI-induced CNS injury by inhibiting excitotoxicity-induced, caspase-independent injury to neuronal processes and cell bodies. As such, the Nmnat1 protective pathway could be a useful therapeutic target for acute and chronic neurodegenerative insults mediated by excitotoxicity. PMID- 22058227 TI - Burn control, an adipocyte-specific function for galectin-12. PMID- 22058229 TI - The nerve injury and the dying neurons: diagnosis and prevention. AB - Following distal nerve injury significant sensory neuronal cell death occurs in the dorsal root ganglia, while after a more proximal injury, such as brachial plexus injury, a sizeable proportion of spinal motoneurons also undergo cell death. This phenomenon has been undervalued for a long time, but it has a significant role in the lack of functional recuperation, as neuronal cells cannot divide and be replaced, hence the resulting nerve regeneration is usually suboptimal. It is now accepted that this cell death is due to apoptosis, as indicated by analysis of specific genes involved in the apoptotic signalling cascade. Immediate nerve repair, either by direct suturing or nerve grafting, gives a degree of neuroprotection, but this approach does not fully prevent neuronal cell death and importantly it is not always possible. Our work has shown that pharmacological intervention using either acetyl-L-carnitine (ALCAR) or N acetyl-cysteine (NAC) give complete neuroprotection in different types of peripheral nerve injury. Both compounds are clinically safe and experimental work has defined the best dose, timing after injury and duration of administration. The efficacy of neuroprotection of ALCAR and NAC can be monitored non-invasively using MRI, as demonstrated experimentally and more recently by clinical studies of the volume of dorsal root ganglia. Translation to patients of this pharmacological intervention requires further work, but the available results indicate that this approach will help to secure a better functional outcome following peripheral nerve injury and repair. PMID- 22058230 TI - The surgical management of painful nerves of the upper limb: a unit perspective. AB - Some patients develop excessive peripheral nerve pain beyond that normally experienced after injury or surgery. Managing this pain can be a difficult and frustrating experience for both the surgeon and patient concerned. We present a system for the classification, assessment and treatment of painful neuromas of the upper limb. PMID- 22058231 TI - A weighting approach to causal effects and additive interaction in case-control studies: marginal structural linear odds models. AB - Estimates of additive interaction from case-control data are often obtained by logistic regression; such models can also be used to adjust for covariates. This approach to estimating additive interaction has come under some criticism because of possible misspecification of the logistic model: If the underlying model is linear, the logistic model will be misspecified. The authors propose an inverse probability of treatment weighting approach to causal effects and additive interaction in case-control studies. Under the assumption of no unmeasured confounding, the approach amounts to fitting a marginal structural linear odds model. The approach allows for the estimation of measures of additive interaction between dichotomous exposures, such as the relative excess risk due to interaction, using case-control data without having to rely on modeling assumptions for the outcome conditional on the exposures and covariates. Rather than using conditional models for the outcome, models are instead specified for the exposures conditional on the covariates. The approach is illustrated by assessing additive interaction between genetic and environmental factors using data from a case-control study. PMID- 22058232 TI - Call to phase out prophylactic use of antimicrobials in livestock. PMID- 22058235 TI - Minister leads topping out of 'world-class' facility at Pirbright. PMID- 22058237 TI - Ups and downs for vulnerable breeds. PMID- 22058238 TI - Veterinary ethics and the humane treatment of animals. PMID- 22058239 TI - Concern expressed about AHVLA's plans for laboratory services. PMID- 22058241 TI - Preventing lungworm. PMID- 22058242 TI - Antimicrobials in the balance: prudence and the precautionary principle. PMID- 22058243 TI - Reducing surgical complications using a safety checklist. PMID- 22058244 TI - Dog breeding. PMID- 22058245 TI - Ingestion of multiple magnets by a dog. PMID- 22058253 TI - [Research on the integration of psychotherapies]. AB - The author analyses metanalytic studies published after 2000, dealing with the common factors of psychotherapeutic interventions. Most studies conclude that there are common factors responsible for the most part of therapeutic effectiveness of the different psychotherapeutic methods. The significance of the specific techniques of the different methods, on the other hand, seems to be secondary, playing role only in the advanced phase of the therapeutic process. The integration of psychotherapies comes into the limelight on the basis of research of common factors. The integration view makes the appearance of new concepts possible, which are presented in short. A further synthesis of higher order concerning the philosophy of psychotherapies becomes possible as well. PMID- 22058254 TI - [Classification of endogenous psychoses. Predictive validity of initial diagnosis based on 5 and 21-33-years of follow-up in a long-term prospective study (Budapest 2000)]. AB - As regards the clinical psychopathological diagnostics, Leonhard's classification of endogenous psychoses published in 1957 contained description of a detailed nosology with claims that the diagnostic categories included in this classification system involve differentiated predictions of course and outcome of the illness. The principal investigator (BP) chose Leonhard's classification system to test these nosological hypotheses via a prospective study of psychotic patients based on their clinical and life history in 1966-67. Validity of the categorial diagnoses given at baseline (female patients n=222; healthy control persons n=54; 1968-1976) was proven by combination of assessments of psychopathological symptoms and personality types at the 5-year follow-up. Moreover, "pure defect" also proved to be valid (84,6%). At the time of the long term follow-up in 1997-2002 (patients: n=125; healthy control persons: n=38) predictive validity of the nine categories was measured empirically and by using a stochastic (Markovian) model, thus combining validity and reliability. Hebephrenias, group of normal persons and of schizophrenias proved to be valid, with diagnostic stabilities of 0,93, 0,89, and 0,93, for the three groups, respectively. In addition, bipolar manic-depressive psychoses and cycloid psychoses were also valid (diagnostic stability of 0,76 in both cases). Unipolar depression was valid (diagnostic stability=0,84) only by forming a "nosological family" based on diagnostic stability and on current status and clinical presentation during the period preceeding the follow-up with regard to other moodcongruent disorders and outcome-diagnosis "healthy control". Validity of systematic paraphrenias (diagnostic stability =0,68) was also in the moderate range. Division of schizophrenias in "systematic vs. non-systematic" nosological categories was inconclusive; the categories of affect-laden paraphrenia, periodic catatonia and systematic catatonias could not be confirmed reliably in this study. PMID- 22058255 TI - [Problematic and pathologic gambling in Hungary: the Hungarian version and use of the South Oaks Gambling Screen (SOGS-HU)]. AB - BACKGROUND AND AIM: Gambling is a form of entertainment with a history of thousand years that has a significant potential for development and has become a widely spread global industry recently. Excessive gambling can take the form of problem, or even pathological gambling. The South Oaks Gambling Screen (SOGS) is the most common measure used for the assessment of problem and pathological gambling. The aim of our study was the development and psychometric analysis of the Hungarian version of the instrument, and its verification on a representative population sample. METHOD: The administration of the instrument was conducted within the frame of the National Household Survey on Addiction Problems, where 2710 persons were interviewed from Hungarian population between 18 and 64 years. RESULTS: The psychometric properties of SOGS-HU are adequate. 65.3% of the respondents had ever gambled. The most popular games are lottery and other number draw games. According to the data obtained by SOGS 1.9 % of the sample was considered to be problem gambler, and 1.4 % of the sample was considered to be pathological gambler. In both groups the proportion of man was higher, while additional risk factors were lower income, lower expected level of education and legal / illegal substance use. CONCLUSION: Based on these results Hungary can be found in the middle-rank of Europe regarding the prevalence of problem and pathological gambling. PMID- 22058256 TI - [Body dissatisfaction and its risk factors: Hungarian adaptation of the Body Shape Questionnaire Short Form 14]. AB - INTRODUCTION: Body dissatisfaction has severe impact on obesity related psychological distress and other mental health problem. The main goals of this study were to present psychometric analysis of the Hungarian version of Body Shape Questionnaire Short Form 14 (BSQ-14), and to explore the risk factors of body dissatisfaction in participants of a health promotion program. METHODS: The study design is a cross-sectional analysis nested in a prospective study. Our respondents (n=377; 61% women; the mean age=38.8 SD=9.58, BMI=27.0 kg/m2 SD=5.52) participate in a countrywide worksite health promotion program targeting weight problems and physical inactivity. Measures included the Hungarian version of Body Shape Questionnaire Short Form 14, Eating Disorder Inventory Bulimia scale, body weight, body high, self-reported lifetime jojo effect (weight cycling), weight dissatisfaction. RESULTS: The one-factor measurement model is supported by confirmatory factor analysis with inclusion two error covariances. Internal consistency of this scale is excellent (Chronbach alpha=0.95). A multivariate analysis revealed that gender (female), actual weight, bulimic tendency, self reported lifetime jojo effect and higher educational attainment are associated with higher body dissatisfaction. CONCLUSIONS: The reliability and construct validity of the Hungarian version of Body Shape Questionnaire Short Form 14 are supported in the present study. Measuring body dissatisfaction might provide a good tool to identify high risk groups and risk factors for psychological distress and to develop optimal intervention programs. PMID- 22058257 TI - [Sleep disturbances and nightmares as risk factors for suicidal behavior among men and women]. AB - INTRODUCTION: Today, more and more international studies analyze the connection between sleep disturbances, including nightmares, and the risk of suicide. The majority of these studies focuses on patients with depression and PTSD; a few studies use community samples. The present paper is based on a community sample research; it examines gender differences in the relationship between nightmares and suicidal behavior (ideation and attempt) during the three years preceding the study. METHODS: The database was derived from the data of the national representative survey Hungaro study 2006, the objective of which was the health status of the Hungarian adult population (N=4642). The five-item version of Athens Insomnia Scale was used for the examination of sleep disturbances; depression was measured with the shortened version of the Beck depression questionnaire. The questions dealing with nightmares were part of the Sleep Quality Questionnaire. Sleep problems, nightmares and depression were considered as risk factors for both suicidal ideation and suicide attempts. Associations were analyzed by logistic regression. The data were corrected for age, gender, education, and financial situation. RESULTS: Our analysis verified the connections between suicidal thoughts and attempts, and nightmares. The results show that the frequent occurrence of nightmares is associated with a nearly four times higher risk of suicide attempts among men (OR=3,89) and a threefold increase among women (OR=1,74). For suicidal thoughts, nightmares correlate with a three times higher risk for men (OR=2,97) and one and the half higher risk for women (OR=1,58). In our sample, frequent nightmares and sleep disorders increase the risk of suicidal behavior more than depression. CONCLUSION: After clinical studies proved the influence of sleep problems in various patient groups, our epidemiological study seem to confirm that nightmares have an independent role in the formation of suicidal behavior. PMID- 22058258 TI - [Association of the different types of substance use behaviors in the Hungarian adult population]. AB - BACKGROUND, AIMS: There are several examples in international literature dealing with the connection between different types of substance use behaviors. Studies mostly report the strengthening effect of one type of substance use on other types as well among Hungarian high school students. In our study the relationship between different substance use behaviors are analyzed on adult population. METHOD: The analysis was carried out within the framework of the Hungarian Population Survey on Addiction Problems (OLAAP) on a sample of 2710 persons from the Hungarian population between 18 and 64 years of age. RESULTS: Lifetime prevalence of abstinence regarding all substance use behaviors in the 18-64 years population is 7.5%. 848% of all subjects have drunk alcohol ever, 55.6% have smoked, 13.1% have consumed prescription drugs and 9.3% have used illicit drugs at least once while lifetime prevalence of abusive prescription drug use is 6.1%. One fourth (24.8%) of the surveyed persons have not used any of the studied substances in the last month. Socio-demographic pattern of different substance use behaviors is rather heterogenic, however descriptive analyses on the relationship between different actual (last month) substance use behaviors in line with the cluster analysis carried out on prevalence data of different substance use behaviors indicate the relatedness of substance use behaviors. CONCLUSION: Our results support the phenomenon called multiple drug use in literature that was observed on a Hungarian high school student sample as well. At the same time however, based on the substance use data regarding adult population, a slightly different cluster structure was identified. PMID- 22058259 TI - Clinical molecular medicine has finally arrived. PMID- 22058260 TI - Dermatomyositis and polymyositis: new treatment targets on the horizon. AB - Polymyositis (PM) and dermatomyositis (DM) are rare idiopathic inflammatory myopathies (IIM) with a presumed autoimmune pathogenesis. Typical features are subacute onset, proximal, symmetric muscle weakness, elevated serum creatine kinase, and mononuclear cell infiltrates in the muscle biopsy. Strong support for an autoimmune pathogenesis comes from histopathological findings in biopsies of affected muscles. Furthermore, the association with autoantibodies supports the notion that immune-mediated inflammation is involved. PM and DM may occur in isolation or in connection with a connective tissue disease or cancer. The current treatment for IIM consists of first-line high-dose steroids and various conventional second-line treatments. Improvements in treatment for IIM are hampered by difficulties in the design of trials and the low incidence and prevalence of the disease. Cytokines and chemokines are factors involved in the inflammatory process in IIM, and are candidates for future therapeutic targets. Preliminary data with anti-tumour necrosis factor therapy are not very promising, but results of blockers of the lymphotoxin signalling pathway are to be awaited. Anti-B cell therapy may be a valuable therapeutic option for treatment of refractory IIM. The effects of anti-interferon-alpha in IIM are to be awaited, as are results of other anti-cytokine therapies and anti-chemokine therapy. Outcome measures to be used in clinical trials in II M include at present the core sets of outcome proposed by the International Myositis Assessment Clinical Study Group (IMACS). PMID- 22058261 TI - Dutch guidelines for diagnosis and treatment of chronic lymphocytic leukaemia 2011. AB - One of the principal responsibilities of the Chronic Lymphocytic Leukaemia (CLL) Working Party of the Dutch/Belgium Haemato-Oncology Foundation for Adults in the Netherlands (HOVON) is to create up-to-date guidelines for CLL . In this article, the revised guidelines for diagnosis and treatment are summarised. Despite recent expansion in treatment options for patients with CLL , the disease remains incurable in most cases and the optimal treatment approach for several subgroups of patients is still unclear. Therefore, it remains highly important to treat patients within clinical studies as much as possible. In this article, the current studies initiated by the HOVON CLL working party are emphasised. PMID- 22058262 TI - New insights into the pathogenesis of chronic myeloid leukaemia: towards a path to cure. PMID- 22058263 TI - Clinical effects of leucoreduction of blood transfusions. AB - For many years filtration for removal of leucocytes from red blood cell (RBC) and platelet transfusions was applied for selected patients to prevent cytomegalovirus (CMV) (re)activation, HLA immunisation and recurrent febrile nonhaemolytic transfusion reactions (FNHTR ). Since the 1980s, there was also growing concern about cancer recurrence and postoperative infections. In this review we discuss the studies on possible benefits of leucoreduction. In 2001 the Dutch Health Council decided that all blood products should undergo leucoreduction by filtration, as a precautionary measure to reduce possible transmission of variant Creutzfeld-Jacob disease (vCJD). The incidences of transfusion-transmitted CMV infection, HLA immunisation and FN HTR are decreased by universal leucoreduction. However, transfusion-related immunomodulation with presumed negative effects on cancer immunosurveillance, postoperative infections or aggravating organ failure, investigated in randomised controlled trials, revealed no support for extended indications for leucoreduction. An exception was seen in cardiac surgery where leucoreduction reduced short-term mortality by approximately 50%. The exact mechanism(s) for this effect is (are) not known. Pro inf lammatory cytokines induced by eucocytecontaining RBC transfusions in combination with the inflammatory response after cardiac surgery may aggravate morbidity and could lead to mortality. In this review we discuss the evidence for the benefits of universal leucoreduction. Based on the available evidence, reversal to the use of buffy-coat depleted RBCs and restricted indications for leucoreduction by filtration (extended with open-heart surgery) is a safe option. PMID- 22058264 TI - Feverless red neck: why worry? Retropharyngeal abscess (RPA) with GABHS. PMID- 22058265 TI - Skin lesions in a HIV-positive female. Cellulitis of the groin region secondary to the skin lesions. PMID- 22058266 TI - A rare cause of abdominal pain. Epiploic appendagitis. PMID- 22058267 TI - Fever and persisting cough. Amoebic liver abscess. PMID- 22058268 TI - Equations estimating renal function in patients with diabetes. PMID- 22058269 TI - Listeria peritonitis in patients on peritoneal dialysis: two cases and a review of the literature. AB - Two cases are reported of patients on continuous ambulatory peritoneal dialysis who presented with peritonitis caused by Listeria monocytogenes. They were successfully treated with intraperitoneal and intravenous administration of amoxicillin. In patients on peritoneal dialysis, Listeria monocytogenes is a very rare cause of peritonitis, with only 11 cases reported to date, and mainly occurring in immunocompromised patients. In contrast to the majority of the reported cases, neither of our patients had received immunosuppressive drugs. To our knowledge, these are the first two cases of Listeria peritonitis reported in the Netherlands. PMID- 22058270 TI - Needlestick injuries and infectious patients in a major academic medical centre from 2003 to 2010. AB - To implement adequate preventive measures in a hospital, the number and nature of occupational exposures to blood must be known. In the Amsterdam Academic Medical Centre a standardised procedure was used to assess all reported occupational exposures to blood from 2003 to 2010. 1601 incidents were reported of which 66% were needlestick accidents. Thirty-five percent of the incidents concerned persons in training and 27% concerned experienced nurses. Twenty-nine percent of accidents occurred during cleaning up after a medical procedure, including the recapping of needles in 6%. In 8% of the accidents the patient was known or found to be infected with hepatitis B or C virus or HIV and in 86% of accidents the personnel were immune to HBV. One case of HCV transmission occurred. The number and nature of the occupational exposures indicate that preventive measures must focus on the replacement of needles by safety devices and on awareness training of experienced nurses and of persons in training. PMID- 22058271 TI - Clinical pathological conference: a non-Hodgkin's lymphoma patient with persistent anaemia after chemotherapy. PMID- 22058272 TI - Inhibitory feedback promotes stability in an oscillatory network. AB - Reliability and variability of neuronal activity are both thought to be important for the proper function of neuronal networks. The crustacean pyloric rhythm (~1 Hz) is driven by a group of pacemaker neurons (AB/PD) that inhibit and burst out of phase with all follower pyloric neurons. The only known chemical synaptic feedback to the pacemakers is an inhibitory synapse from the follower lateral pyloric (LP) neuron. Although this synapse has been studied extensively, its role in the generation and coordination of the pyloric rhythm is unknown. We examine the hypothesis that this synapse acts to stabilize the oscillation by reducing the variability in cycle period on a cycle-by-cycle basis. Our experimental data show that functionally removing the LP-pyloric dilator (PD) synapse by hyperpolarizing the LP neuron increases the pyloric period variability. The increase in pyloric rhythm stability in the presence of the LP-PD synapse is demonstrated by a decrease in the amplitude of the phase response curve of the PD neuron. These experimental results are explained by a reduced mathematical model. Phase plane analysis of this model demonstrates that the effect of the periodic inhibition is to produce asymptotic stability in the oscillation phase, which leads to a reduction in variability of the oscillation cycle period. PMID- 22058273 TI - Explaining pathological changes in axonal excitability through dynamical analysis of conductance-based models. AB - Neurons rely on action potentials, or spikes, to relay information. Pathological changes in spike generation likely contribute to certain enigmatic features of neurological disease, like paroxysmal attacks of pain and muscle spasm. Paroxysmal symptoms are characterized by abrupt onset and short duration, and are associated with abnormal spiking although the exact pathophysiology remains unclear. To help decipher the biophysical basis for 'paroxysmal' spiking, we replicated afterdischarge (i.e. continued spiking after a brief stimulus) in a minimal conductance-based axon model. We then applied nonlinear dynamical analysis to explain the dynamical basis for initiation and termination of afterdischarge. A perturbation could abruptly switch the system between two (quasi-)stable attractor states: rest and repetitive spiking. This bistability was a consequence of slow positive feedback mediated by persistent inward current. Initiation of afterdischarge was explained by activation of the persistent inward current forcing the system to cross a saddle point that separates the basins of attraction associated with each attractor. Termination of afterdischarge was explained by the attractor associated with repetitive spiking being destroyed. This occurred when ultra-slow negative feedback, such as intracellular sodium accumulation, caused the saddle point and stable limit cycle to collide; in that regard, the active attractor is not truly stable when the slowest dynamics are taken into account. The model also explains other features of paroxysmal symptoms, including temporal summation and refractoriness. PMID- 22058274 TI - A dynamical systems analysis of afferent control in a neuromechanical model of locomotion: I. Rhythm generation. AB - Locomotion in mammals is controlled by a spinal central pattern generator (CPG) coupled to a biomechanical limb system, with afferent feedback to the spinal circuits and CPG closing the control loop. We have considered a simplified model of this system, in which the CPG establishes a rhythm when a supra-spinal activating drive is present and afferent signals from a single-joint limb feed back to affect CPG operation. Using dynamical system methods, in a series of two papers we analyze the mechanisms by which this model produces oscillations, and the characteristics of these oscillations, in the closed- and open-loop regimes. In this first paper, we analyze the phase transition mechanisms operating within the CPG and use the results to explain how afferent feedback allows oscillations to occur at a wider range of drive values to the CPG than the range over which oscillations occur in the CPG without feedback, and then to comment on why stronger feedback leads to faster oscillations. Linking these transitions to structures in the phase plane associated with the limb segment clarifies how increased weights of afferent feedback to the CPG can restore locomotion after removal of supra-spinal drive to simulate spinal cord injury. PMID- 22058275 TI - A dynamical systems analysis of afferent control in a neuromechanical model of locomotion: II. Phase asymmetry. AB - In this paper we analyze a closed loop neuromechanical model of locomotor rhythm generation. The model is composed of a spinal central pattern generator (CPG) and a single-joint limb, with CPG outputs projecting via motoneurons to muscles that control the limb and afferent signals from the muscles feeding back to the CPG. In a preceding companion paper (Spardy et al 2011 J. Neural Eng. 8 065003), we analyzed how the model generates oscillations in the presence or absence of feedback, identified curves in a phase plane associated with the limb that signify where feedback levels induce phase transitions within the CPG, and explained how increasing feedback strength restores oscillations in a model representation of spinal cord injury; from these steps, we derived insights about features of locomotor rhythms in several scenarios and made predictions about rhythm responses to various perturbations. In this paper, we exploit our analytical observations to construct a reduced model that retains important characteristics from the original system. We prove the existence of an oscillatory solution to the reduced model using a novel version of a Melnikov function, adapted for discontinuous systems, and also comment on the uniqueness and stability of this solution. Our analysis yields a deeper understanding of how the model must be tuned to generate oscillations and how the details of the limb dynamics shape overall model behavior. In particular, we explain how, due to the feedback signals in the model, changes in the strength of a tonic supra-spinal drive to the CPG yield asymmetric alterations in the durations of different locomotor phases, despite symmetry within the CPG itself. PMID- 22058276 TI - The delayed and noisy nervous system: implications for neural control. AB - Recent advances in the study of delay differential equations draw attention to the potential benefits of the interplay between random perturbations ('noise') and delay in neural control. The phenomena include transient stabilizations of unstable steady states by noise, control of fast movements using time-delayed feedback and the occurrence of long-lived delay-induced transients. In particular, this research suggests that the interplay between noise and delay necessitates the use of intermittent, discontinuous control strategies in which corrective movements are made only when controlled variables cross certain thresholds. A potential benefit of such strategies is that they may be optimal for minimizing energy expenditures associated with control. In this paper, the concepts are made accessible by introducing them through simple illustrative examples that can be readily reproduced using software packages, such as XPPAUT. PMID- 22058277 TI - A sequential Monte Carlo approach to estimate biophysical neural models from spikes. AB - Realistic computational models of neuronal activity typically involve many variables and parameters, most of which remain unknown or poorly constrained. Moreover, experimental observations of the neuronal system are typically limited to the times of action potentials, or spikes. One important component of developing a computational model is the optimal incorporation of these sparse experimental data. Here, we use point process statistical theory to develop a procedure for estimating parameters and hidden variables in neuronal computational models given only the observed spike times. We discuss the implementation of a sequential Monte Carlo method for this procedure and apply it to three simulated examples of neuronal spiking activity. We also address the issues of model identification and misspecification, and show that accurate estimates of model parameters and hidden variables are possible given only spike time data. PMID- 22058278 TI - As iron goes, so goes disease? PMID- 22058279 TI - Beta-thalassemia: from genotype to phenotype. PMID- 22058280 TI - The JAK2 46/1 haplotype: a marker of inappropriate myelomonocytic response to cytokine stimulation, leading to increased risk of inflammation, myeloid neoplasm, and impaired defense against infection? PMID- 22058281 TI - Atypical autoimmune hemolytic anemia. PMID- 22058282 TI - If it ain't broke, don't fix it! PMID- 22058283 TI - Cardiac adaptation to acute and chronic participation in endurance sports. AB - The pervasive public health message is that moderate amounts of endurance exercise help maintain optimal health and reduce cardiovascular risk. While not enough people meet national physical activity guidelines, there are some at the opposite end of the activity spectrum who far exceed the recommended 'dose' of exercise. The cardiovascular health consequences of single and/or multiple (lifelong) 'doses' of high-volume endurance exercise are currently being debated. Recent commentaries, case reports and case series data have posed the question whether you can 'overdose on exercise', and that is the focus of this brief review. PMID- 22058284 TI - Contemporary and evolving risk scoring algorithms for percutaneous coronary intervention. AB - Risk stratification is an essential part of appropriately informing patients electing to undergo percutaneous coronary intervention (PCI). This process is also an integral part of the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery)-pioneered heart team approach in determining the most appropriate revascularisation modality for patients with complex coronary artery disease. The SYNTAX score was pioneered as an anatomical-based risk score to aid in this decision-making process; the lack of clinical variables in this score has, however, been its main limitation. This review examines the important established and evolving contemporary risk models used to aid this risk-stratification process. Risk scores based on clinical and anatomical variables alone and in combination-the latter of which is the subject of continuing research-are all explored. Other areas of discussion include risk scores based on the completeness of revascularisation and emerging concepts such as functional anatomical risk scores and the patient-empowered risk-benefit trade-off between PCI and coronary artery bypass grafting, to help personalise the choice of revascularisation modality. PMID- 22058285 TI - Almanac 2011: cardiomyopathies. The national society journals present selected research that has driven recent advances in clinical cardiology. PMID- 22058286 TI - Diagnosis and management of peripartum cardiomyopathy. PMID- 22058287 TI - Left atrial function: pathophysiology, echocardiographic assessment, and clinical applications. PMID- 22058288 TI - Influence of recruitment strategy on the reach and effect of a web-based multiple tailored smoking cessation intervention among Dutch adult smokers. AB - This study investigated the influence of two different recruitment strategies on the reach and effect of a web-based multiple tailored smoking cessation program. From May 2009 until June 2010, Dutch adult smokers were recruited via mass media or general practices. Those who completed the baseline questionnaire were followed up during 6 weeks (two follow-ups). Differences between the two samples were assessed regarding baseline characteristics, retention rates, quit attempts and 24-hour point prevalence abstinence. Smokers recruited via general practices (N = 409) were significantly lower educated, less addicted, more motivated to quit smoking and to maintain non-smoking, more often female and more often suffering from cardiovascular or respiratory diseases than mass media respondents (N = 1154). They showed higher retention rates and were more likely to report a quit attempt (64.3 versus 50.7%) and abstinence (43.3 versus 33.1%). More respondents could be recruited via mass media, while general practices respondents showed higher retention rates and were more successful in quitting smoking, though these effects became non-significant when controlling for experimental condition and baseline differences. The choice for a particular recruitment strategy appeared to determine the number and type of smokers recruited and might consequently influence the intervention's potential public health impact. PMID- 22058289 TI - Derivation of new human embryonic stem cell lines reveals rapid epigenetic progression in vitro that can be prevented by chemical modification of chromatin. AB - Human embryonic stem cells (hESCs) are pluripotent cell types derived from the inner cell mass of human blastocysts. Recent data indicate that the majority of established female XX hESC lines have undergone X chromosome inactivation (XCI) prior to differentiation, and XCI of hESCs can be either XIST-dependent (class II) or XIST-independent (class III). XCI of female hESCs precludes the use of XX hESCs as a cell-based model for examining mechanisms of XCI, and will be a challenge for studying X-linked diseases unless strategies are developed to reactivate the inactive X. In order to recover nuclei with two active X chromosomes (class I), we developed a reprogramming strategy by supplementing hESC media with the small molecules sodium butyrate and 3-deazaneplanocin A (DZNep). Our data demonstrate that successful reprogramming can occur from the XIST-dependent class II nuclear state but not class III nuclear state. To determine whether these small molecules prevent XCI, we derived six new hESC lines under normoxic conditions (UCLA1-UCLA6). We show that class I nuclei are present within the first 20 passages of hESC derivation prior to cryopreservation, and that supplementation with either sodium butyrate or DZNep preserve class I nuclei in the self-renewing state. Together, our data demonstrate that self-renewal and survival of class I nuclei are compatible with normoxic hESC derivation, and that chemical supplementation after derivation provides a strategy to prevent epigenetic progression and retain nuclei with two active X chromosomes in the self-renewing state. PMID- 22058290 TI - The accumulation and not the specific activity of telomerase ribonucleoprotein determines telomere maintenance deficiency in X-linked dyskeratosis congenita. AB - X-linked dyskeratosis congenita (X-DC) is caused by mutations in the housekeeping nucleolar protein dyskerin. Amino acid changes associated with X-DC are remarkably heterogeneous. Peripheral mononuclear blood cells and fibroblasts isolated from X-DC patients harbor lower steady-state telomerase RNA (TER) levels and shorter telomeres than healthy age-matched controls. Previously, we showed that retroviral expression of recombinant TER, together with expression of recombinant telomerase reverse transcriptase, restored telomere maintenance and proliferative capacity in X-DC patient cells. Using rare X-DC isoforms (DeltaL37 and A386T dyskerin), we showed that telomere maintenance defects observed in X-DC are solely due to decreased steady-state levels of TER. Disease-associated reductions in steady-state TER levels cause deficiencies in telomere maintenance. Here, we confirm these findings in other primary X-DC patient cell lines coding for the most common (A353V dyskerin) and more clinically severe (K314R and A353V dyskerin) X-DC isoforms. Using cell lines derived from these patients, we also examined the steady-state levels of other hinge-ACA motif RNAs and did not find differences in their in vivo accumulations. We show, for the first time, that purified telomerase holoenzyme complexes from different X-DC cells have normal catalytic activity. Our data confirm that dyskerin promotes TER stability in vivo, endorsing the development of TER supplementation strategies for the treatment of X-DC. PMID- 22058291 TI - Displaced fracture of the waist of the scaphoid. AB - A displaced fracture of the scaphoid is one in which the fragments have moved from their anatomical position or there is movement between them when stressed by physiological loads. Displacement is seen in about 20% of fractures of the waist of the scaphoid, as shown by translation, a gap, angulation or rotation. A CT scan in the true longitudinal axis of the scaphoid demonstrates the shape of the bone and displacement of the fracture more accurately than do plain radiographs. Displaced fractures can be treated in a plaster cast, accepting the risk of malunion and nonunion. Surgically the displacement can be reduced, checked radiologically, arthroscopically or visually, and stabilised with headless screws or wires. However, rates of union and deformity are unknown. Mild malunion is well tolerated, but the long-term outcome of a displaced fracture that healed in malalignment has not been established. This paper summarises aspects of the assessment, treatment and outcome of displaced fractures of the waist of the scaphoid. PMID- 22058292 TI - Extra-articular techniques in anterior cruciate ligament reconstruction: a literature review. AB - This annotation considers the place of extra-articular reconstruction in the treatment of anterior cruciate ligament (ACL) deficiency. Extra-articular reconstruction has been employed over the last century to address ACL deficiency. However, the technique has not gained favour, primarily due to residual instability and the subsequent development of degenerative changes in the lateral compartment of the knee. Thus intra-articular reconstruction has become the technique of choice. However, intra-articular reconstruction does not restore normal knee kinematics. Some authors have recommended extra-articular reconstruction in conjunction with an intra-articular technique. The anatomy and biomechanics of the anterolateral structures of the knee remain largely undetermined. Further studies to establish the structure and function of the anterolateral structures may lead to more anatomical extra-articular reconstruction techniques that supplement intra-articular reconstruction. This might reduce residual pivot shift after an intra-articular reconstruction and thus improve the post-operative kinematics of the knee. PMID- 22058293 TI - Effect of intra-articular lesions on the outcome of periacetabular osteotomy in patients with symptomatic hip dysplasia. AB - In order to clarify how intra-articular lesions influence the survival of a periacetabular osteotomy in patients with dysplasia of the hip, we performed an observational study of 121 patients (121 hips) who underwent a transposition osteotomy of the acetabulum combined with an arthroscopy. Their mean age was 40.2 years (13 to 64) and the mean follow-up was 9.9 years (2 to 18). Labral and cartilage degeneration tended to originate from the anterosuperior part of the acetabulum, followed by the femoral side. In all, eight hips (6.6%) had post operative progression to Kellgren-Lawrence grade 4 changes, and these hips were associated with the following factors: moderate osteoarthritis, decreased width of the joint space, joint incongruity, and advanced intra-articular lesions (subchondral bone exposure in the cartilage and a full-thickness labral tear). Multivariate analysis indicated subchondral bone exposure on the femoral head as an independent risk factor for progression of osteoarthritis (p = 0.003). In hips with early stage osteoarthritis, femoral subchondral bone exposure was a risk factor for progression of the grade of osteoarthritis. Although the outcome of transposition osteotomy of the acetabulum was satisfactory, post-operative progression of osteoarthritis occurred at a high rate in hips with advanced intra articular lesions, particularly in those where the degenerative process had reached the point of femoral subchondral bone exposure. PMID- 22058294 TI - The extent of the bone defect affects the outcome of femoral reconstruction in revision surgery with impacted bone grafting: a five- to 17-year follow-up study. AB - We report the results of 79 patients (81 hips) who underwent impaction grafting at revision hip replacement using the Exeter femoral stem. Their mean age was 64 years (31 to 83). According to the Endoklinik classification, 20 hips had a type 2 bone defect, 40 had type 3, and 21 had type 4. The mean follow-up for unrevised stems was 10.4 years (5 to 17). There were 12 re-operations due to intra- and post-operative fractures, infection (one hip) and aseptic loosening (one hip). All re-operations affected type 3 (6 hips) and 4 (6 hips) bone defects. The survival rate for re-operation for any cause was 100% for type 2, 81.2% (95% confidence interval (CI) 67.1 to 95.3) for type 3, and 70.8% (95% CI 51.1 to 90.5) for type 4 defects at 14 years. The survival rate with further revision for aseptic loosening as the end point was 98.6% (95% CI 95.8 to 100). The final clinical score was higher for patients with type 2 bone defects than type 4 regarding pain, function and range of movement. Limp was most frequent in the type 4 group (p < 0.001). The mean subsidence of the stem was 2.3 mm (SD 3.7) for hips with a type 2 defect, 4.3 mm (SD 7.2) for type 3 and 9.6 mm (SD 10.8) for type 4 (p = 0.022). The impacted bone grafting technique has good clinical results in femoral revision. However, major bone defects affect clinical outcome and also result in more operative complications. PMID- 22058295 TI - The effect of aspirin and low-molecular-weight heparin on venous thromboembolism after hip replacement: a non-randomised comparison from information in the National Joint Registry. AB - We compared thromboembolic events, major haemorrhage and death after total hip replacement in patients receiving either aspirin or low-molecular-weight heparin (LMWH). We analysed data from the National Joint Registry for England and Wales linked to an administrative database of hospital admissions in the English National Health Service. A total of 108,584 patients operated on between April 2003 and September 2008 were included and followed up for 90 days. Multivariable risk modelling and propensity score matching were used to estimate odds ratios (OR) adjusted for baseline risk factors. An OR < 1 indicates that rates are lower with LMWH than with aspirin. In all, 21.1% of patients were prescribed aspirin and 78.9% LMWH. Without adjustment, we found no statistically significant differences. The rate of pulmonary embolism was 0.68% in both groups and 90-day mortality was 0.65% with aspirin and 0.61% with LMWH (OR 0.93; 95% CI 0.77 to 1.11). With risk adjustment, the difference in mortality increased (OR 0.84; 95% CI 0.69 to 1.01). With propensity score matching the mortality difference increased even further to 0.65% with aspirin and 0.51% with LMWH (OR 0.77; 95% CI 0.61 to 0.98). These results should be considered when the conflicting recommendations of existing guidelines for thromboprophylaxis after hip replacement are being addressed. PMID- 22058296 TI - Anatomy of the medial femoral circumflex artery with respect to the vascularity of the femoral head. AB - We performed a series of 16 anatomical dissections on Caucasian cadaver material to determine the surgical anatomy of the medial femoral circumflex artery (MFCA) and its anastomoses. These confirmed that the femoral head receives its blood supply primarily from the MFCA via a group of posterior superior nutrient arteries and the posterior inferior nutrient artery. In terms of anastomoses that may also contribute to the blood supply, the anastomosis with the inferior gluteal artery, via the piriformis branch, is the most important. These dissections provide a base of knowledge for further radiological studies on the vascularity of the normal femoral head and its vascularity after dislocation of the hip. PMID- 22058297 TI - The influence of the tibial slope and the size of the intercondylar notch on rupture of the anterior cruciate ligament. AB - It has been suggested that an increased posterior tibial slope (PTS) and a narrow notch width index (NWI) increase the risk of anterior cruciate ligament (ACL) injury. The aim of this study was to establish why there are conflicting reports on their significance. A total of fifty patients with a ruptured ACL and 50 patients with an intact ACL were included in the study. The group with ACL rupture had a statistically significantly increased PTS (p < 0.001) and a smaller NWI (p < 0.001) than the control group. When a high PTS and/or a narrow NWI were defined as risk factors for an ACL rupture, 80% of patients had at least one risk factor present; only 24% had both factors present. In both groups the PTS was negatively correlated to the NWI (correlation coefficient = -0.28, p = 0.0052). Using a univariate model, PTS and NWI appear to be correlated to rupture of the ACL. Using a logistic regression model, the PTS (p = 0.006) and the NWI (p < 0.0001) remain significant risk factors. From these results, either a steep PTS or a narrow NWI predisposes an individual to ACL injury. Future studies should consider these factors in combination rather than in isolation. PMID- 22058298 TI - Simultaneous cemented and cementless total knee replacement in the same patients: a prospective comparison of long-term outcomes using an identical design of NexGen prosthesis. AB - The purpose of this prospective, randomised study was to evaluate the clinical and radiological results comparing the identical cemented or cementless NexGen total knee prostheses implanted bilaterally in the same patient. Sequential simultaneous bilateral total knee replacements were performed in 50 patients (100 knees). There were 39 women and 11 men with a mean age of 58.4 years (51 to 67) who received a cemented prosthesis in one knee and a cementless prosthesis in the other. The mean follow-up was 13.6 years (13 to 14). At final review, the mean Knee Society scores (96.2 (82 to 100) versus 97.7 (90 to 100)), the mean Western Ontario and McMaster Universities osteoarthritis index (34.5 (4 to 59) versus 35.6 (5 to 51)), the mean ranges of knee movement (124 degrees (100 degrees to 140 degrees ) versus 128 degrees (110 degrees to 140 degrees )), mean patient satisfaction (8.1 (SD 1.9) versus 8.3 (SD 1.7)), and radiological results were similar in both groups. The rate of survival of the femoral components was 100% in both groups at 14 years. The rate of survival of the cemented tibial component was 100% and 98% in the cementless tibial component. No osteolysis was identified in either group. Our data have shown no advantage of cementless over cemented components in total knee replacement. PMID- 22058299 TI - The long-term results of a two-stage protocol for revision of an infected total knee replacement. AB - We report the long-term results of the management of neglected chronically infected total knee replacements with a two-stage re-implantation protocol. In 18 of 34 patients (53%) a resistant organism was isolated. All cases were treated by the same surgical team in a specialist centre and had a mean follow-up of 12.1 years (10 to 14). They were evaluated clinically and radiologically using the Knee Society Score (KSS) and the American Knee Society Roentgenographic scoring system, respectively. One patient died after eight years from an unrelated cause and two were lost to follow-up. Three patients (8.8%) developed a recurrent infection for which further surgery was required. The infection was eradicated successfully in 31 patients (91.1%). There was one case of aseptic loosening after 13 years. We found a significant improvement in the KSS at final follow-up (p < 0.001). PMID- 22058300 TI - Management of tibial bone defects with metal augmentation in primary total knee replacement: a minimum five-year review. AB - Bone defects are occasionally encountered during primary total knee replacement (TKR) and cause difficulty in establishing a stable well-aligned bone-implant interface. Between March 1999 and November 2005, 59 knees in 43 patients underwent primary TKR with a metal block augmentation for tibial bone deficiency. In all, six patients (eight knees) died less than four years post-operatively, and four patients (five knees) were lost to follow-up leaving 46 knees in 33 patients available for review at a mean of 78.6 months (62 to 129). The clinical results obtained, including range of movement, American Knee Society and Oxford knee scores, and the Western Ontario and McMaster Universities osteoarthritis index, were good to excellent, with no failures. Radiolucent lines at the block cement-bone interface were noted in five knees (11%) during the first post operative year, but these did not progress. Modular rectangular metal augmentation for tibial bone deficiency is a useful option. No deterioration of the block-prosthesis or block-cement-bone interface was seen at minimum of five years follow-up. PMID- 22058301 TI - Warfarin management in patients on continuous anticoagulation therapy undergoing total knee replacement. AB - We evaluated the safety and efficacy of total knee replacement in patients receiving continuous warfarin therapy. We identified 24 consecutive patients receiving long-term warfarin therapy who underwent total knee replacement between 2006 and 2008 and compared them with a group of age- and gender-matched patients not on long-term anticoagulation. Primary observations were changes in haemoglobin, transfusion rates and complications. Secondary observations were fluctuations in the international normalised ratio (INR) and post-operative range of movement. There was no significant difference between the two groups in pre- or post-operative haemoglobin, incidence of transfusion or incidence of post operative complications. There were no surgical delays due to a high INR level. The mean change in INR during the peri-operative phase was minimal (mean 0.4; SD 0.7). There was no significant difference in the range of movement between the two groups after day two post-operatively. Current American College of Chest Physicians guidelines recommend bridging therapy for high-risk patients receiving oral anticoagulation and undergoing major orthopaedic procedures. We have shown that a safe alternative is to continue the steady-state warfarin peri-operatively in patients on long-term anticoagulation requiring total knee replacement. PMID- 22058302 TI - Safety and outcome of surgical debridement of insertional Achilles tendinopathy using a transverse (Cincinnati) incision. AB - This is a prospective analysis on 30 physically active individuals with a mean age of 48.9 years (35 to 64) with chronic insertional tendinopathy of the tendo Achillis. Using a transverse incision, the tendon was debrided and an osteotomy of the posterosuperior corner of the calcaneus was performed in all patients. At a minimum post-operative follow-up of three years, the Victorian Institute of Sports Assessment scale-Achilles tendon scores were significantly improved compared to the baseline status. In two patients a superficial infection of the wound developed which resolved on antibiotics. There were no other wound complications, no nerve related complications, and no secondary avulsions of the tendo Achillis. In all, 26 patients had returned to their pre-injury level of activity and the remaining four modified their sporting activity. At the last appointment, the mean pain threshold and the mean post-operative tenderness were also significantly improved from the baseline (p < 0.001). In patients with insertional tendo Achillis a transverse incision allows a wide exposure and adequate debridement of the tendo Achillis insertion, less soft-tissue injury from aggressive retraction and a safe osteotomy of the posterosuperior corner of the calcaneum. PMID- 22058303 TI - Heterotopic ossification after total ankle arthroplasty. AB - We evaluated the incidence of heterotopic ossification following total ankle replacement to determine whether the degree of ossification was associated with the clinical outcome. We evaluated 90 ankles in 81 consecutive patients who underwent total ankle replacement, and heterotopic ossification was assessed according to proportional involvement of the ankle joint. Correlation analysis was used to investigate the association between heterotopic ossification and outcome. No significant association was found between the formation of heterotopic ossification and the clinical outcome. The degree of heterotopic ossification in the posterior ankle joint was not significantly correlated with posterior ankle pain (p = 0.929), the American Orthopaedic Foot and Ankle Society score (p = 0.454) or range of movement (p = 0.283). This study indicates that caution should be observed in attributing symptoms and functional limitation to the presence of heterotopic ossification in the posterior ankle joint when considering excision of heterotopic bone after total ankle replacement. PMID- 22058304 TI - Revision surgery following total shoulder arthroplasty: analysis of 2588 shoulders over three decades (1976 to 2008). AB - Our objective was to examine the rate of revision and its predictive factors in patients undergoing total shoulder arthroplasty (TSA). We used prospectively collected data from the Mayo Clinic Total Joint Registry to examine five-, ten- and 20-year revision-free survival following TSA and the predictive factors. We examined patient characteristics (age, gender, body mass index, comorbidity), implant fixation (cemented versus uncemented), American Society of Anesthesiologists class and underlying diagnosis. Univariate and multivariable adjusted hazard rates were calculated using Cox regression analysis. A total of 2207 patients underwent 2588 TSAs. Their mean age was 65.0 years (19 to 91) and 1163 (53%) were women; osteoarthritis was the underlying diagnosis in 1640 shoulders (63%). In all, 212 TSAs (8.2%) were revised during the follow-up period. At five, ten and 20 years, survival rates were 94.2% (95% confidence interval (CI) 93.2 to 95.3), 90.2% (95% CI 88.7 to 91.7) and 81.4% (95% CI 78.4 to 84.5), respectively. In multivariable analyses men had a higher hazard ratio of revision of 1.72 (95% CI 1.28 to 2.31) (p < 0.01) compared with women, and those with rotator cuff disease had a hazard ratio of 4.71 (95% CI 2.09 to 10.59) (p < 0.001) compared with patients with rheumatoid arthritis. We concluded that male gender and rotator cuff disease are independent risk factors for revision after TSA. Future studies are needed to understand the biological rationale for these differences. PMID- 22058305 TI - Efficacy of less invasive posterior lumbar interbody fusion as revision surgery for patients with recurrent symptoms after discectomy. AB - Recurrence of back or leg pain after discectomy is a well-recognised problem with an incidence of up to 28%. Once conservative measures have failed, several surgical options are available and have been tried with varying degrees of success. In this study, 42 patients with recurrent symptoms after discectomy underwent less invasive posterior lumbar interbody fusion (LI-PLIF). Clinical outcome was measured using the Oswestry Disability Index (ODI), Short Form 36 (SF 36) questionnaires and visual analogue scales for back (VAS-BP) and leg pain (VAS LP). There was a statistically significant improvement in all outcome measures (p < 0.001). The debate around which procedure is the most effective for these patients remains controversial. Our results show that LI-PLIF is as effective as any other surgical procedure. However, given that it is less invasive, we feel that it should be considered as the preferred option. PMID- 22058306 TI - Accurate placement of a pelvic binder improves reduction of unstable fractures of the pelvic ring. AB - The aim of this study was to assess the accuracy of placement of pelvic binders and to determine whether circumferential compression at the level of the greater trochanters is the best method of reducing a symphyseal diastasis. Patients were identified by a retrospective review of all pelvic radiographs performed at a military hospital over a period of 30 months. We analysed any pelvic radiograph on which the buckle of the pelvic binder was clearly visible. The patients were divided into groups according to the position of the buckle in relation to the greater trochanters: high, trochanteric or low. Reduction of the symphyseal diastasis was measured in a subgroup of patients with an open-book fracture, which consisted of an injury to the symphysis and disruption of the posterior pelvic arch (AO/OTA 61-B/C). We identified 172 radiographs with a visible pelvic binder. Five cases were excluded due to inadequate radiographs. In 83 (50%) the binder was positioned at the level of the greater trochanters. A high position was the most common site of inaccurate placement, occurring in 65 (39%). Seventeen patients were identified as a subgroup to assess the effect of the position of the binder on reduction of the diastasis. The mean gap was 2.8 times greater (mean difference 22 mm) in the high group compared with the trochanteric group (p < 0.01). Application of a pelvic binder above the level of the greater trochanters is common and is an inadequate method of reducing pelvic fractures and is likely to delay cardiovascular recovery in these seriously injured patients. PMID- 22058307 TI - Physical, mechanical and pharmacological properties of coloured bone cement with and without antibiotics. AB - Coloured bone cements have been introduced to make the removal of cement debris easier at the time of primary and revision joint replacement. We evaluated the physical, mechanical and pharmacological effects of adding methylene blue to bone cement with or without antibiotics (gentamicin, vancomycin or both). The addition of methylene blue to plain cement significantly decreased its mean setting time (570 seconds (SD 4) vs 775 seconds (SD 11), p = 0.01), mean compression strength (95.4 MPa (SD 3) vs 100.1 MPa (SD 6), p = 0.03), and mean bending strength (65.2 MPa (SD 5) vs 76.6 MPa (SD 4), p < 0.001) as well as its mean elastic modulus (2744 MPa (SD 97) vs 3281 MPa (SD 110), p < 0.001). The supplementation of the coloured cement with vancomycin and gentamicin decreased its mean bending resistance (55.7 MPa (SD 4) vs 65.2 MPa (SD 5), p < 0.001).The methylene blue significantly decreased the mean release of gentamicin alone (228.2 ug (SD 24) vs 385.5 ug (SD 26), p < 0.001) or in combination with vancomycin (498.5 ug (SD 70) vs 613 ug (SD 25), p = 0.018) from the bone cement. This study demonstrates several theoretical disadvantages of the antibiotic-loaded bone cement coloured with methylene blue. PMID- 22058308 TI - Forced-air warming and ultra-clean ventilation do not mix: an investigation of theatre ventilation, patient warming and joint replacement infection in orthopaedics. AB - We investigated the capacity of patient warming devices to disrupt the ultra clean airflow system. We compared the effects of two patient warming technologies, forced-air and conductive fabric, on operating theatre ventilation during simulated hip replacement and lumbar spinal procedures using a mannequin as a patient. Infection data were reviewed to determine whether joint infection rates were associated with the type of patient warming device that was used. Neutral-buoyancy detergent bubbles were released adjacent to the mannequin's head and at floor level to assess the movement of non-sterile air into the clean airflow over the surgical site. During simulated hip replacement, bubble counts over the surgical site were greater for forced-air than for conductive fabric warming when the anaesthesia/surgery drape was laid down (p = 0.010) and at half height (p < 0.001). For lumbar surgery, forced-air warming generated convection currents that mobilised floor air into the surgical site area. Conductive fabric warming had no such effect. A significant increase in deep joint infection, as demonstrated by an elevated infection odds ratio (3.8, p = 0.024), was identified during a period when forced-air warming was used compared to a period when conductive fabric warming was used. Air-free warming is, therefore, recommended over forced-air warming for orthopaedic procedures. PMID- 22058309 TI - Intramedullary and total femur replacement in revision arthroplasty as a last limb-saving option: is there any benefit from the less invasive intramedullary replacement? AB - There has been a substantial increase in the number of hip and knee prostheses implanted in recent years, with a consequent increase in the number of revisions required. Total femur replacement (TFR) following destruction of the entire femur, usually after several previous revision operations, is a rare procedure but is the only way of avoiding amputation. Intramedullary femur replacement (IFR) with preservation of the femoral diaphysis is a modification of TFR. Between 1999 and 2010, 27 patients with non-oncological conditions underwent surgery in our department with either IFR (n = 15) or TFR (n = 12) and were included in this study retrospectively. The aim of the study was to assess the indications, complications and outcomes of IFR and TFR in revision cases. The mean follow-up period was 31.3 months (6 to 90). Complications developed in 37% of cases, 33% in the IFR group and 4% in the TFR group. Despite a trend towards a slightly better functional outcome compared with TFR, the indication for intramedullary femur replacement should be established on a very strict basis in view of the procedure's much higher complication rate. PMID- 22058310 TI - Forearm lengthening by distraction osteogenesis in children: a report of 22 cases. AB - We present our experience of forearm lengthening in children with various conditions performed by a single surgeon between 1995 and 2009. A total of 19 children with a mean age of 9.8 years (2.1 to 15.9) at the time of surgery had 22 forearm lengthenings using either an Ilizarov/spatial and Ilizarov circular frame or a monolateral external fixator. The patients were divided into two groups: group A, in whom the purpose of treatment was to restore the relationship between the radius and the ulna, and group B, in whom the objective was to gain forearm length. The mean follow-up after removal of the frame was 26 months (13 to 53). There were ten patients (11 forearms) in group A with a mean radioulnar discrepancy of 2.4 cm (1.5 to 3.3) and nine patients (11 forearms) in group B. In group A, the mean lengthening achieved was 2.7 cm (1.0 to 5.5), with a lengthening index of 11.1 weeks/cm. Equalisation or overcorrection of the discrepancy was achieved in seven of 11 forearms, but lengthening was only partially successful at preventing subluxation or dislocation of the radial head. In group B, the mean lengthening achieved was 3.8 cm (1.9 to 6.8), with a lengthening index of 7.25 weeks/cm. Common complications in both groups were pin site infection and poor regenerate formation. Forearm lengthening by distraction osteogenesis is a worthwhile procedure in children that can improve cosmesis and function, particularly in patients with shortening of both radius and ulna. PMID- 22058311 TI - The use of CRP within a clinical prediction algorithm for the differentiation of septic arthritis and transient synovitis in children. AB - Clinical prediction algorithms are used to differentiate transient synovitis from septic arthritis. These algorithms typically include the erythrocyte sedimentation rate (ESR), although in clinical practice measurement of the C reactive protein (CRP) has largely replaced the ESR. We evaluated the use of CRP in a predictive algorithm. The records of 311 children with an effusion of the hip, which was confirmed on ultrasound, were reviewed (mean age 5.3 years (0.2 to 15.1)). Of these, 269 resolved without intervention and without long-term sequelae and were considered to have had transient synovitis. The remaining 42 underwent arthrotomy because of suspicion of septic arthritis. Infection was confirmed in 29 (18 had micro-organisms isolated and 11 had a high synovial fluid white cell count). In the remaining 13 no evidence of infection was found and they were also considered to have had transient synovitis. In total 29 hips were categorised as septic arthritis and 282 as transient synovitis. The temperature, weight-bearing status, peripheral white blood cell count and CRP was reviewed in each patient. A CRP > 20 mg/l was the strongest independent risk factor for septic arthritis (odds ratio 81.9, p < 0.001). A multivariable prediction model revealed that only two determinants (weight-bearing status and CRP > 20 mg/l) were independent in differentiating septic arthritis from transient synovitis. Individuals with neither predictor had a < 1% probability of septic arthritis, but those with both had a 74% probability of septic arthritis. A two-variable algorithm can therefore quantify the risk of septic arthritis, and is an excellent negative predictor. PMID- 22058312 TI - A comparison of methods of post-operative analgesia in children undergoing limb reconstruction with circular frames. AB - This retrospective study compared post-operative epidural analgesia (E), continuous peripheral nerve blocks (CPNB) and morphine infusion (M) in 68 children undergoing limb reconstruction with circular frames. The data collected included episodes of severe pain, post-operative duration of analgesia, requirement for top-up analgesia, number of osteotomies, side effects and complications. There was a significant difference between the number of episodes of severe pain in patients receiving a morphine infusion and those receiving epidurals or CPNB (M vs E, p < 0.0001; M vs CPNB, p = 0.018). The CPNB group was associated with the lowest incidence of episodes of severe pain and top-up analgesia. Epidural analgesia was associated with significantly more nausea and vomiting than morphine infusion (p = 0.053) and CPNB (p = 0.023). It also had a significantly higher incidence of motor blockade than CPNB (p < 0.01). We found that the most effective method of post-operative analgesia for children undergoing lower limb reconstruction was sciatic nerve catheterisation and continuous infusion. PMID- 22058313 TI - Progressive limitation of knee flexion secondary to an accessory quinticeps femoris muscle in a child: a case report and literature review. AB - We describe a symptomatic, progressive restriction of knee flexion due to an accessory quadriceps femoris in a nine-year-old girl. There was no history or findings of post-injection fibrosis, nor any obvious swelling of the affected quadriceps. At arthroscopy no intra-articular pathology was found. An accessory 'quinticeps femoris' was diagnosed by ultrasonography and MRI. Following excision of the muscle and tendon full flexion of the knee was regained and there was no recurrence of the contracture. PMID- 22058314 TI - Posterior occipitocervical fixation under skull-femoral traction for the treatment of basilar impression in a child with Klippel-Feil syndrome. AB - We present the case of a 15-year-old boy with symptoms due to Klippel-Feil syndrome. Radiographs and CT scans demonstrated basilar impression, occipitalisation of C1 and fusion of C2/C3. MRI showed ventral compression of the medullocervical junction. Skull traction was undertaken pre-operatively to determine whether the basilar impression could be safely reduced. During traction, the C3/C4 junction migrated 12 mm caudally and spasticity resolved. Peri-operative skull-femoral traction enabled posterior occipitocervical fixation without decompression. Following surgery, cervical alignment was restored and spasticity remained absent. One year after surgery he was not limited in his activities. The surgical strategy for patients with basilar impression and congenital anomalies remains controversial. The anterior approach with decompression is often recommended for patients with ventral compression of the medullocervical region, but such procedures are technically demanding and carry a significant risk of complications. Our surgical strategy was an alternative solution. Prior to a posterior cervical fixation, without decompression, skull traction was used to confirm that the deformity was reducible and effective in resolving associated myelopathy. PMID- 22058316 TI - Pectinatus brassicae sp. nov., a Gram-negative, anaerobic bacterium isolated from salty wastewater. AB - A novel Gram-negative, non-spore-forming, strictly anaerobic, heterotrophic bacterium, strain TY(T), was isolated from salty pickle wastewater. Cells were rod-shaped with comb-like flagella, slightly curved and very variable in length. Optimal growth occurred at 28 degrees C and pH 6.5. Cells were resistant to up to 50 g NaCl l(-1). Strain TY(T) produced acid from glycerol, sucrose, glucose, fructose and mannitol. The main fermentation products from glucose were acetic and propionic acids. Tests for acid phosphatase and naphthol-AS-BI phosphohydrolase activities were positive. The major fatty acids were C(14 : 0) DMA (18.7 %), C(15 : 0) (15.4 %), anteiso-C(18 : 1) (15.2 %), C(11 : 0) (13.3 %) and summed feature 5 (C(17 : 1)omega7c and/or C(17 : 2)) (11.0 %). The DNA G+C content was 35.9 mol%. 16S rRNA gene sequence-based phylogenetic analysis indicated that strain TY(T) represented a novel species of the genus Pectinatus (sequence similarity to other members of the genus ranged from 93.2 to 94.8 %). Based on its phenotypic, genotypic and phylogenetic characteristics, strain TY(T) is proposed to represent a novel species, named Pectinatus brassicae sp. nov. (type strain TY(T) = JCM 17499(T) = DSM 24661(T)). PMID- 22058317 TI - Promicromonospora thailandica sp. nov., isolated from marine sediment. AB - A novel actinomycete, strain S7F-02(T), which produced primary branched hyphae and fragmented into V- and Y-shaped bacillary cells, was isolated from marine sediment collected in the Andaman Sea, Trang Province, Thailand. Lysine was found to be the diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell sugars of strain S7F-02(T) were ribose, arabinose and glucose. The characteristic phospholipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. The predominant menaquinone was MK-9(H(4)). The predominant cellular fatty acids were anteiso-C(15 : 0) and iso-C(15 : 0). The G+C content of the genomic DNA of strain S7F-02(T) was 70.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain S7F-02(T) should be classified in the genus Promicromonospora. This strain formed a close association with Promicromonospora citrea DSM 43110(T), with which it shared 99.2 % 16S rRNA gene sequence similarity. DNA-DNA hybridization data together with physiological and biochemical properties showed that strain S7F-02(T) could be readily distinguished from its closest phylogenetic relatives. On the basis of these phenotypic and genotypic data, strain S7F-02(T) is considered to represent a novel species of the genus Promicromonospora, for which the name Promicromonospora thailandica sp. nov. is proposed. The type strain is S7F-02(T) (= BCC 41922(T) = JCM 17130(T)). PMID- 22058318 TI - Kerstersia similis sp. nov., isolated from human clinical samples. AB - Analysis of gyrB gene sequences, (GTG)(5)-primed PCR fingerprinting and biochemical characteristics determined in the Biolog GEN III microtest system were used to differentiate an unnamed Kerstersia species from Kerstersia gyiorum, the type and only named species in this genus. The inability to oxidize D galacturonic and D-glucuronic acids and the ability to oxidize D-serine, along with gyrB gene sequence analysis and (GTG)(5)-PCR fingerprints, readily differentiated the unnamed taxon from the type species. Therefore, we propose to formally classify this unnamed taxon as Kerstersia similis sp. nov. with strain LMG 5890(T) (= CCUG 46999(T)), isolated from a leg wound in the USA in 1983, as the type strain. PMID- 22058319 TI - Exiguobacterium aquaticum sp. nov., a member of the genus Exiguobacterium. AB - A Gram-positive, motile, short rod-shaped, orange pigmented bacterium, designated strain IMTB-3094(T), was isolated from a water sample collected from Tikkar Tal Lake, Haryana, and subjected to detailed polyphasic taxonomic analysis. Strain IMTB-3094(T) possessed most of the phenotypic and chemotaxonomic properties of the genus Exiguobacterium and, based on 16S rRNA gene sequence analysis, was assigned to this genus. Strain IMTB-3094(T) exhibited the highest 16S rRNA gene sequence similarity to Exiguobacterium mexicanum MTCC 7759(T) (99.5 %) followed by Exiguobacterium aurantiacum MTCC 6414(T) (99.1 %), Exiguobacterium aestuarii MTCC 7750(T) (98.0 %), Exiguobacterium profundum MTCC 10851(T) (98.0 %) and Exiguobacterium marinum MTCC 7751(T) (98.0 %). The G+C content of the genomic DNA of strain IMTB-3094(T) was 53.2 mol% and a DNA-DNA relatedness study confirmed that it represents a novel species. The major fatty acids of strain IMTB-3094(T) were iso-C(17 : 0) (16.1 %), anteiso-C(13 : 0) (19.0 %), iso-C(13 : 0) (11.9 %), iso-C(15 : 0) (9.8 %) and iso-C(17 : 1) (12.7 %). The predominant quinones were MK-7 (55.0 %) and MK-6 (26.0 %) with minor amounts of MK-8 (12.0 %). Based on phenotypic, chemotaxonomic and phylogenetic analyses, strain IMTB-3094(T) represents a novel species of the genus Exiguobacterium, for which the name Exiguobacterium aquaticum sp. nov. is proposed. The type strain is IMTB-3094(T) (= MTCC 10958(T) = JCM 17977(T)). PMID- 22058320 TI - Halobacterium piscisalsi Yachai et al. 2008 is a later heterotypic synonym of Halobacterium salinarum Elazari-Volcani 1957. AB - Halobacterium piscisalsi was proposed by Yachai et al. (2008), with a single strain, HPC1-2(T) (= BCC 24372(T) = JCM 14661(T) = PCU 302(T)), which was isolated from fermented fish (pla-ra) in Thailand. According to Yachai et al. (2008), the strain was closely related to Halobacterium salinarum based on 16S rRNA gene sequence comparisons and could be differentiated by low DNA-DNA relatedness values and different biochemical profiles compared with other species of the genus. The reanalysis of the 16S rRNA gene sequences and the DNA-DNA relatedness among H. piscisalsi JCM 14661(T) and H. salinarum strains JCM 8978(T), R1 and NRC-1 revealed that they all had exactly the same 16S rRNA gene sequence and shared more than 70 % DNA-DNA relatedness. In addition, the full length DNA-dependent RNA polymerase subunit B (RpoB) protein sequence of H. piscisalsi JCM 14661(T) (607 amino acids) was the same as that of H. salinarum JCM 8978(T) and showed 94.7 and 96.7 % similarities with those of Halobacterium noricense JCM 15102(T) and Halobacterium jilantaiense JCM 13558(T), respectively. Despite the different biochemical properties described by Yachai et al. (2008), the characteristic phenotypic properties of H. piscisalsi agreed with those in the description of H. salinarum emended by Gruber et al. (2004). Therefore, H. piscisalsi Yachai et al. (2008) should be regarded as a later heterotypic synonym of H. salinarum Elazari-Volcani 1957. PMID- 22058321 TI - Salinisphaera halophila sp. nov., a moderately halophilic bacterium isolated from brine of a salt well. AB - A Gram-stain-negative, moderately halophilic, strictly aerobic bacterium, designated YIM 95161(T), was isolated from brine of a salt well in Yunnan province, China, and subjected to a taxonomic study using a polyphasic approach. Cells of strain YIM 95161(T) were short rods, approximately 0.9-1.4 um long and 0.4-0.6 um wide. Strain YIM 95161(T) grew at 15-40 degrees C (optimum, 25-30 degrees C), 6-29 % (w/v) NaCl (optimum, 14-19 %) and at pH 5.0-8.0 (optimum, pH 7.0). The predominant isoprenoid quinone was Q-8. The major fatty acids (>10 %) were summed feature 8 (C(18 : 1)omega6c and/or C(18 : 1)omega7c) and C(14 : 0). The polar lipids consisted of diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, one unknown phosphoglycolipid and two unknown lipids. The DNA G+C content was 69.5 %. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YIM 95161(T) was a member of the genus Salinisphaera and exhibited sequence similarities of 96.7 %, 95.6 % and 95.4 % to Salinisphaera shabanensis E1L3A(T), Salinisphaera dokdonensis CL ES53(T) and Salinisphaera hydrothermalis EPR70(T), respectively. On the basis of phylogenetic, physiological and chemotaxonomic analysis, strain YIM 95161(T) represents a novel species of the genus Salinisphaera, for which the name Salinisphaera halophila sp. nov. is proposed. The type strain is YIM 95161(T) (= CCTCC AB 2011132(T) = JCM 17431(T)). PMID- 22058322 TI - Enterococcus rivorum sp. nov., from water of pristine brooks. AB - A significant number of Enterococcus strains from pristine waters of two brooks in Finland formed a distinct cluster on the basis of whole-cell protein fingerprinting by one-dimensional SDS-PAGE. The strains shared the following characteristics. Cells were ovoid, Gram-positive-staining and non-spore-forming, appearing singly or in pairs or chains. They were facultatively anaerobic and catalase-negative. Growth in broth containing 6.5 % NaCl or at 45 degrees C was weak or absent. Production of D antigen was variable. The strains tolerated 60 degrees C for 30 min, 40 % bile and tellurite, hydrolysed aesculin strongly and gelatin weakly, produced no acid from hippurate and did not reduce it, grew weakly at 10 degrees C, showed a strong reaction for the Voges-Proskauer test and produced acid from methyl alpha-d-glucoside, mannitol, sorbitol and sucrose, with weak or no production of acid from methyl alpha-d-mannoside, l-arabinose, gluconate and l-xylose. Several of the strains were selected for identification on the basis of sequencing of almost the whole 16S rRNA gene and partial atpA and pheS genes and of (GTG)(5)-PCR fingerprints. Partial atpA and pheS gene sequencing was also performed for those type strains of Enterococcus species without available sequences in the database. The pristine brook isolates formed a novel species, for which the name Enterococcus rivorum sp. nov. (type strain S299(T) = HAMBI 3055(T) = LMG 25899(T) = CCM 7986(T)) is proposed. On the basis of 16S rRNA gene sequence similarity, E. rivorum sp. nov. is related to the Enterococcus faecalis genogoup. It is distinguished from described Enterococcus species on the basis of 16S rRNA, atpA and pheS gene sequences and whole-cell protein and (GTG)(5)-PCR fingerprints. It is most closely related to E. faecalis, but DNA-DNA hybridization confirms it to represent a novel species. PMID- 22058323 TI - Namhaeicola litoreus gen. nov., sp. nov., a member of the family Flavobacteriaceae isolated from seawater. AB - A Gram-staining-negative, non-flagellated, non-gliding and pleomorphic bacterial strain, designated DPG-25(T), was isolated from seawater in a seaweed farm in the South Sea in Korea and its taxonomic position was investigated by using a polyphasic approach. Strain DPG-25(T) grew optimally at 25 degrees C, at pH 7.0 7.5 and in the presence of 2 % (w/v) NaCl. Flexirubin-type pigments were not produced. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain DPG-25(T) formed a cluster with the type strains of Actibacter sediminis, Aestuariicola saemankumensis and Lutimonas vermicola. Strain DPG-25(T) exhibited 16S rRNA gene sequence similarity values of 95.3, 93.1 and 93.6 % to the type strains of Actibacter sediminis, Aestuariicola saemankumensis and L. vermicola, respectively. Strain DPG-25(T) contained MK-6 as the predominant menaquinone and iso-C(15 : 0) and iso-C(17 : 0) 3-OH as the major fatty acids. The major polar lipids detected in strain DPG-25(T) were phosphatidylethanolamine and one unidentified lipid. The DNA G+C content was 39.9 mol%. Differential phenotypic properties and the phylogenetic distinctiveness of strain DPG-25(T) demonstrated that this strain is distinguishable from Actibacter sediminis, Aestuariicola saemankumensis and L. vermicola. On the basis of the data presented here, strain DPG-25(T) represents a novel species in a novel genus of the family Flavobacteriaceae, for which the name Namhaeicola litoreus gen. nov., sp. nov. is proposed. The type strain of Namhaeicola litoreus is DPG-25(T) (= KCTC 23702(T) = CCUG 61485(T)). PMID- 22058324 TI - Mesorhizobium silamurunense sp. nov., isolated from root nodules of Astragalus species. AB - Four rhizobial strains representing a previously defined novel group in the genus Mesorhizobium and isolated from Astragalus species in China were further characterized using a polyphasic approach. Phylogenetic analysis of 16S rRNA gene sequences showed that these Gram-negative bacteria belonged to the genus Mesorhizobium, with Mesorhizobium plurifarium LMG 11892(T) as the closest neighbour sharing a sequence similarity of 99.8 %. Comparative sequence analysis of the atpD, recA, glnII, rpoB, nodC and nifH genes, SDS-PAGE of whole-cell soluble proteins, DNA-DNA hybridization, fatty acid profiles and a series of phenotypic and physiological tests differentiated the novel group from all recognized species of the genus Mesorhizobium. Based on the data obtained in the present and previous studies, this group represents a novel species within the genus Mesorhizobium, for which the name Mesorhizobium silamurunense sp. nov. is proposed. The type strain is CCBAU 01550(T) (= HAMBI 3029(T) = LMG 24822(T)), and could form effective nodules on Astragalus membranaceus, Astragalus adsurgens and Caragana intermedia, and ineffective nodules on Phaseolus vulgaris in cross nodulation tests. PMID- 22058325 TI - Granulicella arctica sp. nov., Granulicella mallensis sp. nov., Granulicella tundricola sp. nov. and Granulicella sapmiensis sp. nov., novel acidobacteria from tundra soil. AB - Four aerobic bacteria, designated MP5ACTX2(T), MP5ACTX8(T), MP5ACTX9(T) and S6CTX5A(T), were isolated from tundra soil of north-western Finland (69 degrees 03' N 20 degrees 50' E). Cells of all isolates were Gram-negative, non-motile rods. Phylogenetic analysis indicated that they belonged to the genus Granulicella of subdivision 1 of the phylum Acidobacteriahttp://dx.doi.org/10.1601/nm.7918. 16S rRNA gene sequence similarity between the new isolates and the type strains of Granulicella aggregans, Granulicella paludicola, Granulicella pectinivorans and Granulicella rosea ranged from 94 to 99 %. Analysis of the RNA polymerase beta subunit (rpoB) gene sequence indicated that the isolates represented novel species of the genus Granulicella (<92 % rpoB sequence similarity between the isolates and members of the genus Granulicella). This was also confirmed by low DNA-DNA relatedness (31 %) between strain S6CTX5A(T) and the type strain of G. pectinivorans, which exhibited 99.1 % 16S rRNA gene sequence similarity and 91.7 % rpoB gene sequence similarity. The isolates grew at pH 3.5-6.5 and at 4-26 degrees C. Sugars were the preferred growth substrates. The major cellular fatty acids were iso-C(15 : 0), C(16 : 1)omega7c and C(16 : 0) and the major isoprenoid quinone was MK-8. The DNA G+C content was 56-60 mol%. On the basis of phylogenetic analysis and chemotaxonomic and physiological data, the isolates represent four novel species of the genus Granulicella, for which the names Granulicella arctica MP5ACTX2(T) (= ATCC BAA 1858(T) = DSM 23128(T)), Granulicella mallensis MP5ACTX8(T) (= ATCC BAA-1857(T) = DSM 23137(T)), Granulicella tundricola MP5ACTX9(T) (ATCC BAA-1859(T) = DSM 23138(T)) and Granulicella sapmiensis S6CTX5A(T) (= LMG 26174(T) = DSM 23136(T)) are proposed. An emended description of the genus Granulicella is also presented. PMID- 22058326 TI - Microbacterium immunditiarum sp. nov., an actinobacterium isolated from landfill surface soil, and emended description of the genus Microbacterium. AB - A Gram-positive, non-endospore-forming bacterium, designated strain SK 18(T), was isolated from surface soil of a landfill site by dilution plating on trypticase soy broth agar. Preliminary characterization of strain SK 18(T) via biochemical tests, analysis of fatty acid methyl esters and partial 16S rRNA gene sequencing placed it within the genus Microbacterium. Analysis of the cell wall indicated that the peptidoglycan was of cross-linkage type B, containing the amino acids lysine and ornithine and with muramic acid in the N-glycolyl form. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, an unidentified phospholipid and an unidentified glycolipid. The major fatty acids of the cell membrane were anteiso-C(17 : 0), anteiso-C(15 : 0) and iso-C(16 : 0). These data further strengthened placement of the strain within the genus Microbacterium. Strain SK 18(T) shared highest 16S rRNA gene sequence similarity (97.2 %) with Microbacterium ulmi DSM 16931(T). Levels of similarity with the type strains of all other recognized Microbacterium species were less than 97.0 %. DNA-DNA hybridization experiments with strain SK 18(T) and its closest relative, M. ulmi DSM 16931(T), revealed a low reassociation value of 39.0 % (sigma = 3.8 %). Moreover, strain SK 18(T) showed a number of differences in phenotypic characteristics (colony colour, catalase activity, hydrolysis of polymers, acid production from sugars and oxidation of various substrates), and its DNA G+C content was also higher than that of M. ulmi DSM 16931(T). These data indicated that strain SK 18(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium immunditiarum sp. nov. is proposed. The type strain is SK 18(T) (= MTCC 7185(T) = JCM 14034(T)). An emended description of the genus Microbacterium is also provided. PMID- 22058327 TI - Identification of a second mimicry epitope from Acanthamoeba castellanii that induces CNS autoimmunity by generating cross-reactive T cells for MBP 89-101 in SJL mice. AB - We had previously reported that Acanthamoeba castellanii (ACA) contains a mimicry epitope for proteolipid protein 139-151 capable of inducing central nervous system (CNS) autoimmunity in SJL/J mice. We now present evidence that ACA also contains a mimicry epitope for myelin basic protein (MBP) 89-101, a derivative from amoebic nicotinamide adenine dinucleotide dehydrogenase subunit 2 (NAD). The epitope, NAD 108-120, contains a discontinuous stretch of six amino acids in the core region (VVFFKNIILIGFL) sharing 46% identity with MBP 89-101 (VHFFKNIVTPRTP; identical residues are underlined). SJL mice immunized with NAD 108-120 develop encephalomyelitis similar to the disease induced by the cognate peptide. We demonstrate that NAD 108-120 induces T cells that cross-react with MBP 89-101; the antigen-sensitized T cells, which produce predominantly T helper (T(h)) 1 and T(h)17 cytokines, transfer disease in naive SJL recipients reminiscent of the disease induced with MBP 89-101. This is the first report to demonstrate that a solitary microbe can induce CNS autoimmunity by generating cross-reactive T cells for multiple myelin antigens. PMID- 22058328 TI - The CD40-CD40L axis and IFN-gamma play critical roles in Langhans giant cell formation. AB - The presence of Langhans giant cells (LGCs) is one of the signatures of systemic granulomatous disorders such as tuberculosis and sarcoidosis. However, the pathophysiological mechanism leading to LGC formation, especially the contribution of the T cells abundantly found in granulomas, has not been fully elucidated. To examine the role of T cells in LGC formation, a new in vitro method for the induction of LGCs was developed by co-culturing human monocytes with autologous T cells in the presence of concanavalin A (ConA). This system required close contact between monocytes and T cells, and CD4+ T cells were more potent than CD8+ T cells in inducing LGC formation. Antibody inhibition revealed that a CD40-CD40 ligand (CD40L) interaction and IFN-gamma were essential for LGC formation, and the combination of exogenous soluble CD40L (sCD40L) and IFN-gamma efficiently replaced the role of T cells. Dendritic cell-specific transmembrane protein (DC-STAMP), a known fusion-related molecule in monocytes, was up regulated during LGC formation. Moreover, knock-down of DC-STAMP by siRNA inhibited LGC formation, revealing that DC-STAMP was directly involved in LGC formation. Taken together, these results demonstrate that T cells played a pivotal role in a new in vitro LGC formation system, in which DC-STAMP was involved, and occurred via a molecular mechanism that involved CD40-CD40L interaction and IFN-gamma secretion. PMID- 22058329 TI - Endogenous osteopontin involvement in laser-induced choroidal neovascularization in mice. AB - PURPOSE: To evaluate the effects of the lack of osteopontin (OPN) and the administration of anti-OPN antibody on inflammation and vascular endothelial growth factor (VEGF) expression in choroidal tissue and on the development of choroidal neovascularization (CNV) after retinal photocoagulation in mice. METHODS: CNV was induced in one eye each of 20 C57BL/6-background OPN-deficient mice or 20 wild-type littermates. In another series of experiments, CNV was induced in 40 C57BL/6 mice treated with intraperitoneal administration of 400 MUg anti-OPN (SLAYGLR) neutralizing antibody or control IgG. Four laser spots were prepared in each eye. At day 14, the size of the CNV was evaluated by high resolution angiography with fluorescein isothiocyanate (FITC)-dextran. Six wild type or six knockout mice also received photocoagulation and processed for histology. mRNA expression of OPN, VEGF, and F4/80 macrophage antigen in laser irradiated choroidal tissues was analyzed at day 3 in wild-type or knockout mice as well as in wild-type mice treated with anti-OPN antibody or control antibody. RESULTS: Photocoagulation upregulated OPN expression in choroidal tissue. Histology did not uncover the effects of the lack of OPN on the healing of laser injury in choroid. The lack of OPN or systemic administration of anti-OPN antibody suppressed mRNA expression of VEGF and macrophage invasion in choroidal tissue. FITC-dextran angiography showed that lacking OPN or systemic anti-OPN antibody reduced the size of laser-induced CNV. CONCLUSIONS: OPN is upregulated in laser-irradiated choroidal tissue. Endogenous OPN is required for macrophage inflammation and VEGF expression in choroidal tissue and for CNV development after retinal photocoagulation in mice. PMID- 22058330 TI - Binocular coordination during reading of blurred and nonblurred text. AB - PURPOSE: Reading a text requires vergence angle adjustments, so that the images in the two eyes fall on corresponding retinal areas. Vergence adjustments bring the two retinal images into Panum's fusional area and therefore, small remaining errors or regulations do not lead to double vision. The present study evaluated dynamic and static aspects of the binocular coordination when upcoming text was blurred. METHODS: Binocular eye movements and accommodation responses were simultaneously measured for 20 participants while reading single, nonblurred sentences and while the text was blurred as if it were seen by a person in whom the combination of refraction and accommodation deviated from the stimulus plane by 0.5 D. RESULTS: Text comprehension did not change, even though fixation times increased for reading blurred sentences. The disconjugacy during saccades was also not affected by blurred text presentations, but the vergence adjustment during fixations was reduced. Further, for blurred text, the overall vergence angle shifted in the exo direction, and this shift correlated with the individual heterophoria. Accommodation measures showed that the lag of accommodation was slightly larger for reading blurred sentences and that the shift in vergence angle was larger when the individual lag of accommodation was also larger. CONCLUSIONS: The results suggest that reading comprehension is robust against changes in binocular coordination that result from moderate text degradation; nevertheless, these changes are likely to be linked to the development of fatigue and visual strain in near reading conditions. PMID- 22058331 TI - Extracellular matrix elasticity modulates TGF-beta-induced p38 activation and myofibroblast transdifferentiation in human tenon fibroblasts. AB - PURPOSE: Extracellular matrix and the cytokine TGF-beta influence scar formation in an interdependent fashion. In this study, the impact of extracellular matrix elasticity on TGF-beta-induced signal transduction and myofibroblast transdifferentiation was examined. METHODS: Primary human tenon fibroblasts were seeded on collagen-coated glass coverslips (rigid environment) or collagen or polyacrylamide gels (elastic environment) of different compliance and stimulated with TGF-beta. Myofibroblast transdifferentiation was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis for the marker gene alpha-smooth muscle actin (SMA), and SMA incorporation into stress fibers was determined by confocal immunofluorescence microscopy. CTGF transcription was assessed by RT-qPCR. Signaling pathways were examined by Western blot using phosphospecific antibodies and by immunofluorescence microscopy. RESULTS: TGF-beta-dependent myofibroblast transdifferentiation was enhanced in a stiff environment. Increasing matrix elasticity attenuated TGF-beta-induced myofibroblast transdifferentiation and the associated CTGF expression. TGF-beta-induced p38 activation was reduced on elastic substrates. CONCLUSIONS: The results suggest that matrix elasticity influences TGF-beta-dependent activation of p38 signaling and subsequent myofibroblast transdifferentiation. Biomechanical cues represent an important determinant of scarring processes. Therefore, cellular signals elicited by mechanotransduction deserve consideration in the design of novel antifibrotic strategies. PMID- 22058332 TI - Roles of AMP-activated protein kinase in diabetes-induced retinal inflammation. AB - PURPOSE: AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. The purpose of the present study was to elucidate the roles of AMPK in the pathogenesis of diabetic retinopathy using the known AMPK activators resveratrol and AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) in a mouse model. METHODS: C57BL/6 mice with streptozotocin-induced diabetes were treated with resveratrol orally at 50 mg/kg for 7 days or with AICAR intraperitoneally at 100 mg/kg 24 hours before death. Retinal protein levels of phosphorylated and total AMPK, phosphorylated nuclear factor (NF)-kappaB p65, intercellular adhesion molecule (ICAM)-1, and vascular endothelial growth factor (VEGF) were evaluated by Western blot analysis or enzyme-linked immunosorbent assay. Retinal activity of sirtuin (SIRT)1 was measured by deacetylase fluorometric assay. Leukocyte adhesion to the retinal vasculature was examined with a concanavalin A lectin perfusion-labeling technique. RESULTS: Induction of diabetes in mice led to retinal AMPK dephosphorylation, which was significantly reversed by either resveratrol or AICAR. Either resveratrol or AICAR significantly reversed SIRT1 deactivation and NF-kappaB phosphorylation, both of which were induced in the diabetic retina. Administration of resveratrol to diabetic mice significantly reduced diabetes-induced retinal leukocyte adhesion, together with retinal expression of ICAM-1 and VEGF. CONCLUSIONS: The present findings reveal that diabetes-induced retinal inflammation stems from downregulation of the AMPK pathway, leading subsequently to SIRT1 deactivation and NF-kappaB activation. The data also suggest the potential use of the AMPK activator resveratrol as a therapeutic agent for diabetic retinopathy. PMID- 22058333 TI - The development of crowding and interocular interactions in a resolution acuity task. AB - PURPOSE: To investigate the impact of interocular similarities of a surround stimulus on foveal resolution acuity in the normally developing visual system. METHODS: Liquid crystal shutter goggles synchronized with the monitor frame rate were used to present a Landolt C and surround bars to one or both eyes, in monocular, dichoptic, half-binocular, and binocular viewing conditions. Resolution acuity was measured under each condition in 56 normally sighted children (7 to 14 years of age) and 22 adults (21 to 38 years of age). The effect of the surround bars (crowding) was tested in a subgroup of nine children, and 10 adults. RESULTS: Across all age groups resolution acuity was significantly better in the binocular condition than in the other three viewing conditions (binocular summation), and was significantly better in the half-binocular (with target presented to the test eye and bars presented to both eyes) than in the dichoptic condition (target presented to test eye and bars presented to the nontested eye only). In children, but not in adults, resolution acuity was significantly better without than with bars. CONCLUSIONS: The interocular similarities may explain the better visual resolution in the half-binocular condition than in the dichoptic condition for all age groups tested. The results suggest that interocular interactions underpinning resolution acuity under these viewing conditions are developed in early childhood. The foveal crowding effect was found to be apparent at the beginning of school age, and diminished with maturation. PMID- 22058334 TI - Expression and role of VEGF in the adult retinal pigment epithelium. AB - PURPOSE: Despite a lack of active angiogenesis, VEGF is expressed in nearly every adult tissue, and recent evidence suggests that VEGF may serve as a survival factor for both vascular and nonvascular tissues. VEGF blockade is a widely used treatment for neovascular diseases such as wet age-related macular degeneration (AMD). Therefore, it was sought in this study to evaluate the expression and role of endogenous VEGF in RPE. METHODS: VEGF and VEGFR2 expression in the murine retina were assessed during development. Bevacizumab was used to neutralize VEGF in ARPE-19 cells, and the effects on cell survival and apical microvill were assessed by TUNEL and SEM, respectively. VEGF was systemically neutralized in vivo by adenoviral-mediated overexpression of soluble VEGFR1 (sFlt). RPE and choriocapillaris were analyzed by transmission electron microscopy (TEM). Changes in gene expression were evaluated by quantitative real-time PCR. RESULTS: VEGF expression was detected in the developing RPE as early as embryonic day (E) 9.5, whereas VEGFR2 expression by RPE began nonuniformly between postnatal (P) day 6.5 and P8.5. VEGF neutralization in vitro led to increased apoptosis and reduced microvilli density and length. Systemic VEGF neutralization led to transient degenerative changes; RPE were vacuolated and separated from photoreceptor outer segments, and choriocapillaris fenestrations were decreased. VEGF levels were elevated in RPE of Ad-sFlt1 mice at day 4 postinfection, and there was increased expression of the neurotrophic factor CD59a at day 14. CONCLUSIONS: These results indicate that VEGF plays a critical role in survival and maintenance of RPE integrity. Potential undesired off-target effects should be considered with chronic use of anti-VEGF agents. PMID- 22058335 TI - Effect of acute intraocular pressure elevation on the monkey optic nerve head as detected by spectral domain optical coherence tomography. AB - PURPOSE: To determine whether acutely elevated IOP alters optic nerve head (ONH) structural parameters characterized in vivo using spectral domain optical coherence tomography (SD-OCT). METHODS: Five rhesus macaques were tested under isoflurane anesthesia. SD-OCT images of the ONH of both eyes were acquired 30 minutes after IOP was stabilized to 10 mm Hg and 60 minutes after stabilization to 45 mm Hg. The internal limiting membrane, Bruch's membrane/retinal pigment epithelium, neural canal opening (NCO), and anterior lamina cribrosa surface (ALCS) were delineated using custom software. Differences in SD-OCT structural parameters between the two IOP levels were assessed using generalized estimating equations. In six eyes of three animals, images were acquired after 10 minutes and 30 minutes of IOP stabilization to 10 mm Hg (control experiment). RESULTS: Acute IOP elevation resulted in a reduction in prelaminar tissue thickness (mean, -47 MUm; SD, 25 MUm; P = 0.002), rim volume (-0.05 mm(3), 0.02 mm(3); P = 0.002), rim width (-30 MUm, 7 MUm; P = 0.002), and in an increase in NCO depth (38 MUm, 15 MUm; P = 0.002). An increase in ALCS depth was significant relative to peripheral Bruch's membrane (48 MUm, 24 MUm; P = 0.002) but not relative to the NCO. No significant parameter changes were detected in the control eyes. CONCLUSIONS: Surface compliance changes in the normal monkey ONH primarily reflect prelaminar and peripapillary deformation. SD-OCT compliance testing will further our understanding of the effects of IOP on the ONH and help improve and validate numerical models of ONH biomechanics. PMID- 22058336 TI - Associations between genetic polymorphisms of insulin-like growth factor axis genes and risk for age-related macular degeneration. AB - PURPOSE: To investigate whether insulin-like growth factor (IGF) axis genes, together with a novel dietary risk factor, the dietary glycemic index (dGI), and body mass index (BMI) affect the risk for age-related macular degeneration (AMD). METHODS: This case-control study involved 962 subjects originally recruited through the Age-Related Eye Disease Study (AREDS) Genetic Repository. After those with missing covariates or invalid calorie intake (n = 23), diabetes (n = 59), and non-Caucasian race (n = 16) were excluded, 864 participants were used, including 209 AREDS category 1 participants (control group), 354 category 2 or 3 participants (drusen group), and 301 category 4 participants (advanced AMD group). A total of 25 single-nucleotide polymorphisms (SNPs) selected from IGF-1 (n = 9), IGF-2 (n = 1), IGF binding protein 1 (IGFBP1; n = 3), IGFBP3 (n = 3), acid-labile subunit of IGFBP (IGFALS; n = 2), IGF1 receptor (IGF1R; n = 4), and IGF2R (n = 3) were genotyped. SNP-AMD associations were measured with genotype, allele chi(2) tests and Armitage's trend test. Odds ratios (OR), 95% confidence intervals (CIs), and SNP-exposure interactions were evaluated by multivariate logistic regression. RESULTS: One SNP (rs2872060) in IGF1R revealed a significant association with advanced AMD (P-allele = 0.0009, P-trend = 0.0008; the significance level was set at 0.05/25 = 0.002 for multiple comparisons). The risk allele (G) in the heterozygous and homozygous states (OR, 1.67 and 2.93; 95% CI, 1.03-2.71 and 1.60-5.36, respectively) suggests susceptibility and an additive effect on AMD risk. Further stratification analysis remained significant for both neovascularization (OR, 1.49 and 2.61; 95% CI, 0.90-2.48 and 1.39-4.90, respectively) and geographic atrophy (OR, 2.57 and 4.52; 95% CI, 0.99-6.71 and 1.49-13.74, respectively). The G allele interaction analysis with BMI was significant for neovascularization (P = 0.042) but not for geographic atrophy (P = 0.47). No significant interaction was found with dGI. CONCLUSIONS: These data suggest a role of IGF1R on the risk for advanced AMD in this group of subjects. PMID- 22058337 TI - Polarized distribution of heme transporters in retinal pigment epithelium and their regulation in the iron-overload disease hemochromatosis. AB - PURPOSE: FLVCR, BCRP, and PCFT/HCP-1 represent the three heme transporters identified thus far in mammalian cells, but there is very little known about their expression and regulation in the retina. In this study, the expression of these transporters in mouse retina and retinal pigment epithelium (RPE) and their regulation in the iron-overload disease hemochromatosis were examined. METHODS: The expression of FLVCR, BCRP, and PCFT in mouse retina and primary mouse RPE cells was studied by RT-PCR and immunofluorescence. Polarized localization of the transporters in RPE was studied by co-localization using a specific marker of the RPE apical membrane. Uptake of heme in primary RPE cells was determined using zinc-mesoporphyrin, a fluorescent heme analogue. The regulation of heme transporters by iron overload was studied in two genetic models of hemochromatosis (HFE-null mouse and HJV-null mouse) and in two nongenetic models of iron overload (cytomegalovirus infection and treatment with ferric ammonium citrate). RESULTS: All three heme transporters were expressed in the retina and RPE. In the RPE, the expression of FLVCR was restricted to the apical membrane, and the expression of BCRP and PCFT was restricted to the basolateral membrane. In all cases of iron overload, the expression of FLVCR and PCFT was upregulated and that of BCRP was downregulated. CONCLUSIONS: Hemochromatosis is associated not only with excessive accumulation of free iron in the retina and RPE but also with excessive accumulation of heme. Since heme is toxic at high levels, as is free iron, heme-induced oxidative damage may also play a role in hemochromatosis associated retinal pathology. PMID- 22058338 TI - Responses of rabbit retinal ganglion cells to subretinal electrical stimulation using a silicon-based microphotodiode array. AB - PURPOSE: With subretinal prostheses, retinal ganglion cells (RGCs) are activated by electrical stimulation of the retinal neural network. The aim of this study was to evaluate the efficacy of silicon-based solar cells in evoking RGC responses by electrically stimulating the photoreceptor side of an isolated retina. METHODS: A light-bleached retina of an adult New Zealand White rabbit was placed with its photoreceptor side down onto a silicon chip that consisted of a 4 * 4 microphotodiode array (MPDA). The stimulating current was elicited by activating the solar cell with a 532-nm laser light source. Responses of the ON and OFF alpha RGCs on electrical stimulation were recorded extracellularly. Recorded RGCs were then injected with 4% N-(2-aminoethyl)-biotinamide hydrochloride to allow cell type identification. RESULTS: Using a design that includes a circumvented ground electrode, the authors successfully evoked spiking responses by the ON and OFF alpha RGCs in an isolated rabbit retina using low light power to activate the MPDA (equivalent to 39 MUC/cm(2)). The charge density dependent response and the frequency-dependent pair-pulse suppression were characterized. The spike latency of the RGC responses triggered by electrical stimulation was equivalent to the latency of its light response, which supports the hypothesis that the activation is mediated by the retinal neural network. CONCLUSIONS: Reliable activation of RGCs by electrical stimulation in vitro using an MPDA demonstrates the feasibility of developing solar cell-based subretinal prostheses that potentially could be developed into a power-free device able to restore vision. PMID- 22058339 TI - Light-initiated bonding of amniotic membrane to cornea. AB - PURPOSE: Suturing amniotic membrane to cornea during surgery is time consuming, and sutures may further damage the eye. The authors introduce a novel sutureless, light-activated technique that securely attaches amnion to cornea through protein protein crosslinks. METHODS: Cryopreserved human amniotic membrane, stained with Rose Bengal (RB), was placed over a full-thickness wound in deepithelialized rabbit cornea and was treated with green laser. The intraocular pressure that broke the seal (IOP(L)) was measured, and adhesion was measured with a peel test. The influences on bonding strength of fluence, irradiance, RB concentration, and amnion surface bonded were measured. Epithelial cell migration on treated amnion and keratocyte viability after bonding were also measured. The involvement in the bonding mechanism of oxygen, singlet oxygen, and association of RB with stromal collagen was investigated. RESULTS: Sealing amniotic membrane over cornea using 0.1% RB and 150 J/cm(2) at 532 nm produced an IOP(L) of 261 +/- 77 mm Hg ex vivo and 448 mm +/- 212 mm Hg in vivo. The ex vivo IOP(L) increased with increasing fluence (50-150 J/cm(2)). Equivalent IOP(L) was produced for bonding basement membrane or stromal amnion surfaces. The bonding treatment was not toxic to keratocytes but slightly reduced the migration of corneal epithelial cells on amnion ex vivo. Mechanism studies indicated that RB forms two complexes with amnion stromal collagen, that bonding requires oxygen, and that singlet oxygen mediates protein crosslinking. CONCLUSIONS: A rapid, light-activated technique produces strong, immediate bonding between amnion and cornea and merits further evaluation for ocular surface surgeries. PMID- 22058340 TI - Intraocular safety and pharmacokinetics of hexadecyloxypropyl-cidofovir (HDP-CDV) as a long-lasting intravitreal antiviral drug. AB - PURPOSE: To evaluate the intraocular safety and pharmacokinetics of hexadecyloxypropyl-cidofovir (HDP-CDV), the hydrolysis product of HDP-cyclic-CDV, a long-lasting intravitreal cidofovir prodrug for cytomegalovirus (CMV) retinitis. METHODS: HDP-cyclic-CDV was suspended in phosphate-buffered saline (PBS) at 37 degrees C and formation of HDP-CDV was monitored by high-performance liquid chromatography (HPLC) analysis for 30 weeks. The safety and pharmacokinetics of HDP-CDV intravitreal injections were studied using New Zealand Red rabbits and (14)C labeled HDP-CDV. Ocular tissues from five time points (1, 3, 7, 14, and 35 days) were analyzed by scintillation counting and HPLC to characterize the pharmacokinetics. RESULTS: During the hydrolysis study, approximately 35% of the HDP-cyclic-CDV was converted to HDP-CDV. Evaluation of safety found no toxicity after intravitreal injection of HDP-CDV up to 28 MUg/eye. Intravitreal pharmacokinetics of HDP-CDV in the retina, choroid, and vitreous followed a two-phase elimination process and elimination half-lives of 8.4 days (retina), 6.9 days (choroid), and 6.2 days (vitreous). In the retina, cidofovir and an unknown metabolite were detected in the first 2 weeks, and the maximum metabolite concentrations were present 48 hours after the maximum HDP-CDV concentration. CONCLUSIONS: HDP-cyclic CDV, under simulated physiologic conditions, slowly converts to HDP-CDV, another potent anti-CMV prodrug that may be taken up by retinal cells and metabolized further to the active antiviral metabolite, cidofovir diphosphate. Taken together, these observations help to explain the ability of a single intravitreal dose of HDP-cyclic-CDV to prevent viral retinitis for up to 68 days in a rabbit model. PMID- 22058341 TI - Assessing efficacy of combined riboflavin and UV-A light (365 nm) treatment of Acanthamoeba trophozoites. AB - PURPOSE: To assess the Acanthamoeba trophozoite viability in vitro and treatment of Acanthamoeba keratitis in a hamster model using ultraviolet light A (UV-A) and riboflavin (B2). METHODS: A sample of Acanthamoeba sp. cultured was transferred to a 96-well plate and exposed to B2 and the UV-A light (365 nm wavelength) at a power density of 3 mW/cm(2), 8 mm spot diameter, for 30 minutes. The exposure was done in triplicate. Control groups were prepared in triplicate as well: blank control, UV-A only, riboflavin only, and dead control. Cell viability assessment was done using the trypan blue dye exclusion method. Acanthamoeba keratitis was induced in Chinese hamsters; who were randomly assigned to one of the animal groups: UV-A + B2, propamidine isethionate (Brolene; Sanofi-Aventis, Ellerslie, Auckland, Australia), UV-A + B2 + propamidine isethionate (Brolene), only UV-A, only B2, and blank. Throughout the 14 days after treatment the animals were examined clinically. Histology and clinical scores of all groups were compared. RESULTS: The in vitro study showed no difference between the treatment group UV-A + B2 and the control groups. In the hamster keratitis model a significant improvement of clinical score was observed for the groups propamidine isethionate (Brolene) and UV-A + B2 + propamidine isethionate (Brolene) (P = 0.0067). Also a significant worsening of clinical score was observed in the other groups: UV-A + B2 group (P = 0.0084), only UV-A (P = 0.0078), B2 only (P = 0.0084), and blank (P = 0.0082). No difference was observed between propamidine isethionate (Brolene) and UV-A + B2 + propamidine isethionate (Brolene). CONCLUSIONS: The adjunctive use of UV-A and B2 therapy did not demonstrate antitrophozoite activity; in vivo UV-A and B2 did not demonstrate efficacy in this model. PMID- 22058342 TI - Choroidal thickness in healthy Chinese subjects. AB - PURPOSE: To study posterior choroidal thickness and its profile based on location in a healthy Chinese population and to determine its correlation with age and refractive error. METHODS: A total of 210 healthy volunteers (420 eyes) with no ophthalmic disease history were recruited. Choroidal scans were obtained for all eyes using enhanced depth imaging spectral-domain optical coherence tomography. Subfoveal choroidal thickness (SFCT) and choroidal thickness at 1 mm/3 mm temporal, nasal, superior, and inferior to the fovea were measured. RESULTS: The choroid was thickest underneath the fovea (261.93 +/- 88.42 MUm). At 1 mm and 3 mm to the fovea, the choroid temporally was thicker than nasally. Mean SFCT in subjects younger than 60 years of age were 294.63 +/- 75.90 MUm, and no correlation between SFCT and age was noted. Mean SFCT in subjects older than 60 years of age was 196.52 +/- 74.42 MUm, much thinner than that for subjects younger than 60 years of age. A significant negative correlation was found between SFCT and age in subjects older than 60 years of age. CONCLUSIONS: Age is critical for evaluation of choroidal thickness. However, SFCT has no correlation with age in subjects younger than 60 years of age. In subjects older than 60 years of age, SFCT was significantly negatively correlated with age, and decreased by 5.40 MUm for each year of life. PMID- 22058343 TI - AAHA anesthesia guidelines for dogs and cats. AB - Safe and effective anesthesia of dogs and cats rely on preanesthetic patient assessment and preparation. Patients should be premedicated with drugs that provide sedation and analgesia prior to anesthetic induction with drugs that allow endotracheal intubation. Maintenance is typically with a volatile anesthetic such as isoflurane or sevoflurane delivered via an endotracheal tube. In addition, local anesthetic nerve blocks; epidural administration of opioids; and constant rate infusions of lidocaine, ketamine, and opioids are useful to enhance analgesia. Cardiovascular, respiratory, and central nervous system functions are continuously monitored so that anesthetic depth can be modified as needed. Emergency drugs and equipment, as well as an action plan for their use, should be available throughout the perianesthetic period. Additionally, intravenous access and crystalloid or colloids are administered to maintain circulating blood volume. Someone trained in the detection of recovery abnormalities should monitor patients throughout recovery. Postoperatively attention is given to body temperature, level of sedation, and appropriate analgesia. PMID- 22058344 TI - Exposure circumstances and outcomes of 48 households with 57 cats exposed to toxic lily species. AB - Ingestion of Lilium or Hemerocallis spp. by cats can result in renal failure. The objectives of this study were to determine the foreknowledge of lily toxicity of owners of cats that were exposed to lilies and to obtain historical, clinical and outcome information on the exposures. A survey was done of cat owners reporting indoor exposures to lilies to the Animal Poison Control Center (APCC) during April 2009. Forty eight individuals, (57 cats) were included. Sixty nine percent of cat owners said they could recognize a lily and 27% knew that lilies were toxic prior to their cats' exposures. Most lilies were obtained from grocery or other stores, and were purchased by the owners or as gifts to the cat owners. Owners who were unaware of lily toxicity frequently left the flowers where the cats had access to them, whereas in households where the toxicity was known the cats actively sought out the flowers. Of the cats in this study 93% received prompt veterinary care, and 87% either developed no signs or had brief signs that resolved. Five percent had evidence of renal insufficiency at final follow-up and another 5 percent of cats were euthanized due to renal failure. PMID- 22058345 TI - Pilot evaluation of a vacuum-assisted biopsy instrument for percutaneous renal biopsy in dogs. AB - Kidney biopsies in dogs are commonly obtained using automated spring-loaded biopsy instruments. Interpretation of biopsies from dogs with glomerular disease requires examination of at least 5-10 glomeruli, with at least two biopsies usually required for full evaluation. The purpose of this study was to compare quality and interpretability of renal biopsies obtained from healthy dogs with a large-gauge, vacuum-assisted biopsy instrument versus two biopsies obtained with a spring-loaded biopsy needle. Twenty dogs were randomized into two groups, and percutaneous, ultrasound-guided renal biopsies were evaluated using standard criteria. There were no significant differences in the number of biopsies that contained renal tissue, cortex, or medulla. Biopsies obtained with either instrument contained an adequate number of glomeruli and an equivalent number of arterioles and severity of tissue compression. Differences included easier penetration of the renal capsule and collection of sufficient tissue for interpretation with only one instrument pass when using the vacuum-assisted device (vs two passes required with the spring-loaded instrument). Before use in client-owned dogs, future studies should evaluate whether these differences are clinically relevant advantages in the diagnostic evaluation of dogs with kidney disease, and determine the prevalence and severity of complications when using this larger gauge device. PMID- 22058346 TI - Comparison of subjective and objective intradermal allergy test scoring methods in dogs with atopic dermatitis. AB - An intradermal allergy test (IDT) is an important diagnostic tool for identifying offending allergens in canine atopic dermatitis. No standardized method of scoring an IDT has been described. The purpose of this study was to determine whether there is a correlation between a conventional, subjective IDT scoring method based on perceived wheal diameter, erythema, and turgor (0-4+) and an objective scoring method based on measuring wheal diameter alone. Thirty-four atopic dogs were skin tested with 68 different allergens. All skin tests were performed according to standard procedures, and any IDT score >=2+ was considered clinically significant. When the subjective IDT scores were compared with the objective IDT scores in all dogs, there was a moderate level of correlation overall (r=0.457; P <0.0001). The highest level of agreement between subjective and objective scores was noted with the reactions assigned subjective scores of "0" and "2+." Overall, there was a slight level of agreement between subjective and objective scores based on clinical significance (i.e., subjective scores >=2+; kappa=0.20; P <0.0001). In conclusion, the authors believe that the objective scoring method used in this study may provide a point of reference for inexperienced individuals (dermatology residents, veterinarians, technicians) when learning to grade an IDT. PMID- 22058347 TI - Presurgical antiseptic efficacy of chlorhexidine diacetate and providone-iodine in the canine preputial cavity. AB - Antiseptic flushing of the canine prepuce and its exclusion from the surgical field are recommended before abdominal surgery to reduce the risk of bacterial contamination. The authors cultured the preputial cavity of 60 dogs prior to and following flushing with 0.05% chlorhexidine diacetate, 1% povidone-iodine, or 0.9% saline control. Bacterial growth was evaluated using a semiquantitative method, and bacterial organisms were subsequently identified. There were no significant differences between povidone-iodine and the saline control in any of the variables assessed. Chlorhexidine resulted in a significant decrease in the proportion of positive postflush cultures compared with povidone-iodine. Although not significant, the difference in adverse reactions between povidone-iodine (25%) and chlorhexidine diacetate (5%) suggests clinical relevance. Based on the results of this study, a 2 min flush with 0.05% chlorhexidine diacetate is recommended for presurgical preparation of the preputial cavity. PMID- 22058348 TI - Blastomyces dermatitidis prostatic and testicular infection in eight dogs (1992 2005). AB - This was a retrospective case study of eight dogs diagnosed with prostatic or testicular B. dermatitidis infection. Signalment, clinical presentation, diagnostic procedures, and treatment options were evaluated. Review of medical records of dogs diagnosed with blastomycosis at the University of Illinois Veterinary Teaching Hospital from 1992 to 2005 yielded four dogs with prostatic blastomycosis (PB) and four dogs with testicular blastomycosis (TB). Three of the four dogs with PB and all four dogs with TB had evidence of urogenital disease. Three dogs with PB had an elevated body temperature and all had systemic disease. All dogs with TB had a normal body temperature, and three had systemic disease and one had clinical signs limited to testicular disease. Cytology or histopathology was used to diagnose PB or TB. Treatment included itraconazole or fluconazole with or without nonsteroidal anti-inflammatory drugs. PB and TB are infrequently recognized and may be under diagnosed due to failure to specifically evaluate these tissues. PB or TB should be considered in the evaluation and staging of male dogs with blastomycosis. Male dogs with urogenital signs should be evaluated via prostatic or testicular cytology or histopathology since proper identification and management of PB or TB may improve overall treatment success. PMID- 22058349 TI - Hyperadrenocorticism in 10 dogs with skin lesions as the only presenting clinical signs. AB - Ten dogs that had skin lesions as the only presenting signs of hyperadrenocorticism (HAC) and as the owners' primary complaint are described. Dogs were included if the initial examination was for skin disease, there were no signs of systemic illness on initial presentation and there was a confirmed diagnosis of HAC by specific screening tests. Dogs were excluded if they had a severe disease that might interfere with screening tests for HAC or if the screening tests were not diagnostic. There were five males and five females; six dogs were intact. Nine dogs were diagnosed at >=7 years. Eight dogs weighed <=10 kg. Alopecia was present in nine dogs. Eight dogs had bacterial pyoderma, five had hyperpigmentation, and four had thin skin. One dog had unresolved dermatophytosis. Skin lesions resolved after treatment in eight dogs. One dog was not treated and one was lost to follow-up. This study showed that skin lesions may be the only clinical signs of HAC. The presence of the more common clinical signs of HAC, such as a non-pruritic, truncal alopecia and/or thin skin, without any systemic signs of HAC and/or the presence of poorly responsive skin infections warrant screening for this disease. PMID- 22058350 TI - Elective and emergency surgical management of adrenal gland tumors: 60 cases (1999-2006). AB - Sixty-one adrenal gland tumors were surgically removed from 60 dogs. Fifty-two dogs underwent elective adrenalectomy and 8 dogs underwent emergency adrenalectomy for acute adrenal hemorrhage. Size of adrenal tumors ranged from 10 mm to 80 mm. Histopathology confirmed a diagnosis of adrenocortical tumor in 47 dogs, 26 of which were malignant. Pheochromocytoma was diagnosed in 11 dogs. Six dogs had tumor invasion of the caudal vena cava. Of the seven dogs that did not survive the perioperative period, four underwent emergency adrenalectomy. No dogs with tumor invasion of the caudal vena cava died perioperatively. Perioperative morality rates were 5.7% for dogs that underwent elective adrenalectomy and 50% for dogs that underwent emergency adrenalectomy for acute adrenal hemorrhage. Median survival time was 492 days for the 53 dogs that survived the perioperative period. Of the factors analyzed, only adrenal tumor size and the presence of acute adrenal hemorrhage had predictive values for perioperative mortality. Those dogs that survived the perioperative period had extended survival times of up to 1,590 days. The mortality rate associated with elective adrenalectomy in dogs may be lower than previously reported. Dogs with very large tumors or acute adrenal hemorrhage may have a more guarded prognosis. PMID- 22058351 TI - Severe esophageal injuries occurring after general anesthesia in two cats: case report and literature review. AB - Two healthy cats underwent elective surgical procedures under general anesthesia. One developed severe esophagitis leading to esophageal rupture, mediastinitis, and pyothorax. The other cat developed esophageal stricture, diverticulum formation, and suspected iatrogenic perforation. Both cats had signs of dysphagia and regurgitation beginning a few days after anesthesia. The first cat also had severe dyspnea due to septic pleural effusion and pneumomediastinum. In the second cat, endoscopy revealed diffuse esophagitis, an esophageal stricture, and a large esophageal diverticulum. Rupture of the esophageal wall occurred while inflating the esophagus for inspection. Due to the poor prognosis, both cats were euthanized. Necropsy revealed severe esophageal changes. Postanesthetic esophagitis has been previously described in dogs and cats; however, severe life threatening esophageal injuries rarely occur as a sequel to general anesthesia. To the authors' knowledge, esophageal rupture secondary to perianesthetic reflux has never been reported in cats. PMID- 22058352 TI - Alveolar rhabdomyosarcoma in a juvenile labrador retriever: case report and literature review. AB - A 7 mo old Labrador retriever presented for evaluation of facial swelling associated with a 5 cm oral mass extending caudally from the upper third premolar on the left side. Cytology revealed an atypical population of round cells of undetermined origin. A diagnosis of alveolar rhabdomyosarcoma (RMS) was reached via histopathology and confirmed with positive immunohistochemical staining for desmin. In humans, RMSs have a well-described round cell cytologic appearance. Few descriptions of veterinary cases of RMS exist. This report describes the cytologic appearance of alveolar RMS in a young dog and both summarizes and compares findings throughout the veterinary and human literature. PMID- 22058353 TI - Oronasal fistula repair utilizing a temporalis muscle flap in a dog with severe trismus. AB - A 9 yr old spayed female cocker spaniel presented for evaluation of an invasive maxillary squamous cell carcinoma. Curative intent surgery and radiation therapy allowed for local control of the neoplasm; however, the development of a persistent oronasal fistula prevented a complete recovery. A temporalis myofascial rotation flap allowed for successful resolution of the maxillary defect. Implementation of the flap was relatively simple and was associated with few complications. PMID- 22058354 TI - Severe ulcerative and granulomatous pinnal lesions with granulomatous sebaceous adenitis in unrelated vizslas. AB - Granulomatous sebaceous adenitis (GSA) is uncommon in dogs; however, certain breed predilections exist. In this report, three cases of GSA in unrelated vizslas have been described. All cases initially presented with episodes of otitis externa followed by severe inner pinnal lesions. In one case, multifocal coalescing inner pinnal ulceration appeared 4 wk prior to the occurrence of the skin lesions. The other two cases presented with simultaneous pinnal and skin lesions following episodes of bilateral otitis. The pinnae were diffusely erythematous and had multiple coalescing erosions and ulcers. The body lesions consisted of multifocal alopecia, papules, and fine scales. Biopsies of the skin and pinnae confirmed GSA. Two dogs responded to treatment with synthetic retinoids and cyclosporin A, respectively. One dog was not treated, and the owners preferred euthanasia when the ear lesions recurred and did not respond to glucocorticoids. To the best of the authors' knowledge, GSA with multifocal coalescing ulcerative pinnal lesions has not previously been reported. PMID- 22058355 TI - Remifentanil/isoflurane anesthesia in five dogs with liver disease undergoing liver biopsy. AB - Remifentanil is a synthetic opioid with direct action on MU opioid receptors. It has an ultrashort duration of action, and its elimination is independent of hepatic or renal function. The anesthetic management of five dogs with nonuniform liver disease and requiring liver biopsy via celiotomy is described. Remifentanil and isoflurane were used for induction and maintenance of anesthesia. Intraoperative analgesia was provided by a constant rate infusion of remifentanil. Remifentanil, in combination with isoflurane, was safely and successfully used in five cases for the balanced anesthesia of dogs with hepatic diseases requiring liver biopsy via celiotomy. PMID- 22058356 TI - Clinical resolution of nasal aspergillosis following therapy with a homeopathic remedy in a dog. AB - A 6 yr old, male, neutered Weimaraner was treated homeopathically for nasal aspergillosis after failing to respond to two treatments of topical (intranasal) clotrimazole and oral amoxicillin trihydrate/clavulanate potassium. Computed tomography, rhinoscopy, fungal culture, and cytology previously confirmed the diagnosis. At presentation for homeopathic treatment, the dog had aggressive left sided sinusitis and rhinitis with destruction of nasal turbinates and severe bouts of epistaxis. Erosion and depigmentation of the nasal planum were evident. After two treatments with homeopathic aurum metallicum, resolution of clinical signs occurred and clearance of the aspergillosis organisms was documented by computed tomographic scan, rhinoscopy, and histopathology. Homeopathic aurum metallicum may be beneficial in treating cases of canine nasal aspergillosis. PMID- 22058357 TI - Cutaneous and systemic blastomycosis, hypercalcemia, and excess synthesis of calcitriol in a domestic shorthair cat. AB - A 9 yr old domestic shorthair cat was diagnosed with cutaneous and pulmonic blastomycosis. Severe persistent ionized hypercalcemia and excess circulating concentration of calcitriol were documented in association with blastomycosis. Ionized hypercalcemia resolved when the granulomatous lesions of blastomycosis resolved and the calcitriol levels decreased. PMID- 22058358 TI - Infectious endocarditis and chylothorax in a cat. AB - A 6 yr old domestic longhair cat was evaluated for progressive weight loss, weakness, and dyspnea. Results of a physical examination and electrocardiogram were suggestive of cardiac disease. Thoracic radiographs revealed pleural effusion, which thoracocentesis revealed was consistent with chyle. An echocardiogram was performed, and aortic valve endocarditis with secondary aortic insufficiency was presumptively diagnosed. The cat was treated with broad spectrum oral antibiotics and palliative cardiac medications. Two days after discharge, the cat's dyspnea returned, and it died suddenly. Histopathology and culture confirmed Pseudomonas bacterial endocarditis of the aortic valve. Bacterial endocarditis in the cat has rarely been reported in the literature. This case described heart failure and chylothorax resulting from bacterial endocarditis. PMID- 22058359 TI - Intrathoracic lipoma in a cat. AB - A 10 yr old female cat presented for an acute onset of back arching, regurgitation, and open mouth breathing. Radiographs indicated the presence of a large intrathoracic mass. Computed tomography confirmed the presence of a large mass of fatty density in the dorso-caudal mediastinum. The mass was removed via right intercostal thoracotomy, and histopathology confirmed the mass as a lipoma. The cat was continuing to recover well as of 21 mo after surgery. This is the first reported case of an intrathoracic lipoma in a cat. PMID- 22058360 TI - Computed tomography of a cat with primary intratracheal lymphosarcoma before and after systemic chemotherapy. AB - A 12 yr old male neutered domestic shorthair cat presented with worsening tachypnea of 1 mo duration and open mouth breathing. Radiographs revealed tracheal narrowing at the thoracic inlet. Computed tomography (CT) revealed a contrast enhancing 8-cm long fusiform mass within the dorsal tracheal membrane. Tracheobronchoscopy confirmed the presence of the tracheal mass at the thoracic inlet, and lymphoma was diagnosed based on uniformly atypical lymphoid cells on aspirated bronchoalveolar lavage fluid. The cat was treated with combination chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin, and prednisolone. Thoracic radiographs and CT performed 1 mo after completion of the 6 mo chemotherapy protocol revealed resolution of the tracheal mass. The cat remained clinically normal at 21 mo after treatment. PMID- 22058361 TI - Resolution of a proteinuric nephropathy associated with Babesia gibsoni infection in a dog. AB - A 4 yr old male castrated Labrador retriever was evaluated for a short history of inappetance, lethargy, small-bowel diarrhea, polyuria, and polydipsia. Clinicopathologic abnormalities were consistent with protein-losing nephropathy and renal azotemia. Expansive infectious disease testing implicated Babesia gibsoni via whole blood polymerase chain reaction. Renal histopathology results were consistent with membranoproliferative glomerulonephritis and immune complex deposition. The dog was treated with azithromycin, atovaquone, and one dose of corticosteroids/cyclophosphamide. Three months after therapy was completed, the dog was clinically healthy, and all clinicopathologic abnormalities (including Babesia species polymerase chain reaction) had resolved. Atypical presentations of Babesia gibsoni should be considered with proteinuric nephropathy. PMID- 22058362 TI - Intramedullary epidermoid cyst in the thoracic spine of a dog. AB - A 5 yr old female spayed mastiff was evaluated for a 3-4 mo history of paraparesis and 3 days of acutely worse paraparesis and incontinence. On magnetic resonance imaging, a spinal cord lesion was present at the ninth thoracic vertebra. The lesion was hyperintense on T2-weighted images (T2-W), and a hyperintense rim was present on T1-weighted postcontrast images. Histologic examination showed a cystic mass lined by squamous epithelial cells. Histopathologic diagnosis was an intramedullary epidermoid spinal cyst. Epidermoid cyst should be a differential diagnosis in young dogs with a myelopathy and an intramedullary spinal cord lesion on magnetic resonance imaging examination. PMID- 22058363 TI - Ophthalmomyiasis externa in a puppy due to Cuterebra infestation. AB - An 8 wk old Scottish terrier was evaluated for a 2*2 cm mass located directly adjacent to the lateral canthus of the right eye. Examination revealed a well developed Cuterebra larva at the lateral aspect of the orbital cavity, anchored at the lateral canthus. The larva was manually removed under general anesthesia, and the eyelid margin was repaired. Systemic and topical antibiotics along with systemic anti-inflammatory treatment were instituted. The lesion healed completely, revealing a normal functional right eye 10 days after removal of the Cuterebra larva. Careful manual removal of the larva is recommended along with correction of any resultant conformational defects. The remaining cavity can be left to heal; however, antibiotic therapy is recommended. PMID- 22058364 TI - Endoscopic diagnosis of a pylorogastric intussusception with spontaneous resolution. AB - A 7 mo old intact female golden retriever was evaluated for acute vomiting. Abdominal radiographs revealed a possible gastric foreign body. Upper gastrointestinal endoscopy revealed an edematous, tubular antral mass, which on further evaluation was determined to be a pylorogastric intussusception based on radiographic, endoscopic, and surgical findings. Spontaneous resolution of the intussusception occurred upon surgical exploration of the abdomen. Histopathology of a full-thickness gastric biopsy revealed vascular congestion consistent with an intussusception, but did not indicate the primary cause. The dog recovered uneventfully from surgery and had no further vomiting during the 6 mo follow-up period. This case was significant as it was the first report of pylorogastric intussusception diagnosed using endoscopy. This description of the unique endoscopic appearance of pylorogastric intussusception will be useful for the veterinary endoscopist. PMID- 22058365 TI - Leptospirosis in a dog with uveitis and presumed cholecystitis. AB - A 7 yr old castrated male Australian shepherd dog was examined for acute change in iris color, lethargy, and anorexia. Uveitis, acute renal failure, and presumed cholecystitis were diagnosed. Based on clinical findings, leptosporosis was suspected, and the dog was treated with antibiotics and supportive care. The dog made a complete recovery, and leptospirosis was confirmed on convalescent titers. Due to the zoonotic potential, leptospirosis should be considered in cases of uveitis, as well as possible cholecystitis. PMID- 22058366 TI - Mesenteric vascular thrombosis associated with disseminated abdominal visceral hemangiosarcoma in a cat. AB - An adult castrated male cat was evaluated because of a 4 day history of lethargy and partial anorexia. Physical examination revealed abdominal pain with a palpable fluid wave. Cytologic and biochemical analyses of peritoneal effusion were suggestive of septic peritonitis. On surgical exploration of the abdomen, the mesenteric vessels had no palpable pulses and they contained gross thromboses. The intestines were white with no visible peristalsis. Necropsy findings included disseminated, poorly differentiated hemangiosarcoma throughout the abdomen. Mesenteric arterioles contained fibrin thrombi. To the author's knowledge, no previous reports exist of complete mesenteric vascular thrombosis associated with disseminated abdominal visceral hemangiosarcoma in a cat. PMID- 22058367 TI - Hypocalcemia following surgical treatment of metastatic anal sac adenocarcinoma in a dog. AB - A 9 yr old neutered male mixed-breed dog was presented for an anal sac apocrine gland adenocarcinoma with regional nodal metastases. At presentation, ionized calcium was 1.91 mmol/L (NOVA Stat reference range, 1.1-1.3 mmol/L). Surgical excision of the primary tumor and metastatic lymph nodes was performed. Following surgery, symptomatic hypocalcemia was noted. Repeated ionized calcium measurements confirmed hypocalcemia, and hypercalcemia of malignancy panels suggested parathyroid gland suppression as the cause. The calcium normalized with parenteral calcium administration, but calcium later became elevated with tumor recurrence and an increase in the parathormone-related peptide. Disrupted calcium homeostasis is a potential complication following the treatment of long-standing humoral hypercalcemia of malignancy. PMID- 22058368 TI - Fanconi syndrome in four non-basenji dogs exposed to chicken jerky treats. AB - Four small-breed dogs were diagnosed with acquired Fanconi syndrome. All dogs ate varying amounts of chicken jerky treats. All dogs were examined for similar clinical signs that included, but were not limited to, lethargy, vomiting, anorexia, diarrhea, and altered thirst and urination. The quantity of chicken jerky consumed could not be determined; however, based on the histories obtained, the chicken jerky treats were a significant part of the diet and were consumed daily by all dogs. Extensive diagnostic testing eliminated other causes of the observed clinical signs, such as urinary tract infection and rickettsial disease. Glucosuria in the face of euglycemia or hypoglycemia, aminoaciduria, and metabolic acidosis confirmed the diagnosis of Fanconi syndrome. All dogs received supportive care, including IV fluids, antibiotics, gastroprotectants, and oral nutritional supplements. Three dogs exhibited complete resolution of glucosuria, proteinuria, and the associated azotemia; however, one dog remained azotemic, resulting in a diagnosis of chronic kidney disease. PMID- 22058369 TI - Treatment of a malignant pheochromocytoma in a dog using 131I metaiodobenzylguanidine. AB - A 12 yr old castrated male Yorkshire terrier was presented with a history of an inoperable pheochromocytoma. Physical examination revealed a large, midabdominal mass. Neurologic examination was normal at presentation. An abdominal computed tomography scan revealed a 215 cm(3) mass in the region of the right kidney. Forty-eight hours after IV injection of 370 megabecquerels (MBq, equivalent to10 millicuries [mCi]) of metaiodobenzylguanidine labeled with radioactive iodine ([(131)I]MIBG), standard planar scintigraphy was performed. A diffuse area of moderate uptake was noted in the midabdominal region. The dog experienced stable disease for 1.5 mo after injection based on a follow-up computed tomography (CT) scan; however, 5 mo after injection, repeat CT imaging revealed progression of the tumor, and a second IV injection of 370 MBq (10 mCi) of [(131)I]MIBG was administered. The dog died 3 wk after the second injection as a result of gastrointestinal blood loss that was believed to be caused by compression-induced bowel ischemia by the mass. A full necropsy was not performed, but the mass was removed for histologic evaluation, which confirmed the diagnosis of pheochromocytoma. This report is the first to document the treatment of canine pheochromocytoma using [(131)I]MIBG. PMID- 22058370 TI - Two cases of paraprostatic cysts in castrated male dogs. AB - Two castrated male dogs presented for evaluation of tenesmus. Presurgical evaluations included complete physical examinations, serum biochemistry, abdominal ultrasonography, and MRI (case 2 only). Paraprostatic cysts were diagnosed in both cases based on the results of abdominal ultrasonography, MRI, and histopathology of tissue samples obtained during exploratory laparotomy. To the authors' knowledge, the two cases presented herein are the first documented cases of paraprostatic cysts that developed after castration in male dogs. Paraprostatic cysts should be considered in the differential diagnoses for castrated male dogs with prostatic disease. PMID- 22058371 TI - Fusion podoplasty for the management of chronic pedal conditions in seven dogs and one cat. AB - Eight animals underwent fusion podoplasties for the treatment of chronic interdigital furunculosis (n=3), ectrodactyly (n=1), digit abnormalities associated with tendonectomy (n=1), redundant indertigital skin (n=1), conformational deformity (n=1), and necrotizing fasciitis of the paw (n=1). Median duration of bandaging was 14 days, and median duration of hospitalization was 5 days. Four dogs had dehiscence, which occurred at a mean time of 11 days after surgery. Clinical abnormalities necessitating podoplasty resolved in six animals and improved in two. Six animals had normal ambulation and two dogs had slight weight-bearing lameness after a median follow-up time of 29 mo. Fusion podoplasty may be recommended as a salvage procedure for the treatment of various chronic pedal diseases in dogs and cats. PMID- 22058372 TI - Typical and atypical manifestations of Anaplasma phagocytophilum infection in dogs. AB - Eighteen clinically ill dogs, naturally infected with Anaplasma phagocytophilum, were examined at a veterinary practice in Baxter, Minnesota. A clinical examination, complete blood cell count, enzyme- linked immunosorbent assay (ELISA) for A phagocytophilum, Borrelia burgdorferi, and Ehrlichia canis antibodies and Dirofilaria immitis antigen, and a polymerase chain reaction test for A phagocytophilum DNA were obtained for all dogs. Physical examination findings included fever, arthropathy, lymphadenopathy, epistaxis, acute gastritis, cervical hyperpathia, and central nervous system dysfunction. Complete blood cell count abnormalities included thrombocytopenia, morulae in neutrophils, anemia, leukopenia, eosinopenia, lymphopenia, and monocytosis. Seroreactivity to A phagocytophilum was found in 61%, B burgdorferi antibodies in 17%, and D immitis antigen in 5% of the dogs. Fever, arthropathy, neurologic dysfunction, and epistaxis are clinical syndromes that can be associated with A phagocytophilum infection. Treatment with doxycycline resulted in rapid resolution of clinical signs in all dogs. PMID- 22058373 TI - Canine schistosomiasis in Kansas: five cases (2000-2009). AB - This is a retrospective case series consisting of five dogs diagnosed with schistosomiasis. The purpose of this article is to report the presence of naturally occurring canine schistosomiasis in Kansas and to provide clinical details regarding schistosomiasis. Medical records of dogs diagnosed with schistosomiasis from 2000 to 2009 were reviewed, and information extracted included signalment, history, clinical signs, diagnostic test results, treatment, and outcome. Affected dogs were primarily medium to large breed and young to middle aged. All dogs were considered outdoor dogs, with three having known access to surface water. Common clinical signs included gastrointestinal disease and signs associated with hypercalcemia. Fecal flotation was negative in all dogs in contrast to fecal saline sedimentation and fecal polymerase chain reaction, which were both positive in all dogs in which it was performed. All dogs treated specifically for schistosomiasis fully recovered. This article describes the first reported cases of canine schistosomiasis in the Midwest and the first reported case of intestinal intussusception secondary to schistosomiasis. Recognizing that canine schistosomiasis is present in Kansas and possibly other Midwestern states should prompt veterinarians to perform appropriate diagnostic investigation in suspect animals as the diagnosis is straight forward and relatively inexpensive. PMID- 22058374 TI - Extended-spectrum beta-lactamases in German isolates belonging to the emerging monophasic Salmonella enterica subsp. enterica serovar Typhimurium 4,[5],12:i:- European clone. PMID- 22058375 TI - Update in hyper- and hypogonadotropic amenorrhea. AB - BACKGROUND: Amenorrhea is a relatively common condition that is present in up to 5% of adult women at any time. The clinical significance of a lack of regular menstrual cycles extends beyond reproductive concerns. Episodes of amenorrhea as short as 90 d may have implications for bone and cardiovascular health. Prolonged amenorrhea, depending upon its underlying cause, can be a harbinger of substantial cardiovascular risk. MATERIALS AND METHODS: This is an update of recent medical literature on this topic. RESULTS: The past few years have been marked by a greater appreciation of the early presentation of common ovulatory disorders, such as polycystic ovary syndrome, and less common disorders, such as premature ovarian insufficiency/failure. The long-term implications of functional hypothalamic amenorrhea and its genetic origins have also been further elucidated. Finally, health consequences of these and other menstrual disorders are increasingly well defined, with firmer clinical endpoints rather than merely risk factor assessments. PMID- 22058376 TI - Approach to the patient with new-onset diabetes after transplant (NODAT). AB - New-onset diabetes after transplantation (NODAT) refers to the occurrence of diabetes in previously nondiabetic persons after organ transplantation. The incidence rates of NODAT vary by organ transplanted and posttransplant interval. The estimated rates at 12 months posttransplant are 20-50% for kidney transplants, 9-21% for liver transplants, and approximately 20% for lung transplants. NODAT is associated with increased risks of graft rejection, infection, cardiovascular disease, and death. Besides the traditional risk factors for type 2 diabetes (age, family history, obesity, and ethnicity), exposure to immunosuppressive agents often precedes the occurrence of NODAT. Identification of risk factors through pretransplant screening is desirable, as is prompt diagnosis and appropriate treatment. NODAT is consistent with type 2 diabetes and responds to the usual antidiabetes agents. However, severe hyperglycemia during the early posttransplant period may necessitate the use of iv insulin infusion. Also, high-dose glucocorticoid therapy for induction of immunosuppression (or treatment of acute rejection) may require the use of insulin therapy for glycemic control. After hospital discharge, close monitoring of blood glucose during the first month and every 3 months for the first year is recommended. Consideration should be given to drug toxicities or interactions when prescribing antidiabetes agents in the posttransplant patient. In addition to hyperglycemia, the control of comorbidities such as dyslipidemia and hypertension needs to be optimized. Future areas of investigation include the development of immunosuppressive regimens with minimal diabetogenic effects, determination of the role of glycemic control on graft survival, and interventions for primary prevention of NODAT. PMID- 22058377 TI - Squeezing the pituitary gland. PMID- 22058378 TI - (18)F-FDG-PET/CT imaging of ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) demonstrating increased (18)F-FDG uptake. PMID- 22058379 TI - Management of adolescents with polycystic ovary syndrome. PMID- 22058380 TI - The response to hypoglycemia: a role for the opioid system? PMID- 22058386 TI - Vaginal atrophy. PMID- 22058388 TI - Bupivacaine extended release liposome injection does not prolong QTc interval in a thorough QT/QTc study in healthy volunteers. PMID- 22058389 TI - A case completion curriculum for clinical dental education: replacing numerical requirements with patient-based comprehensive care. AB - The aim of this article is to describe the development and implementation of a case completion curriculum as a new clinical education model for the predoctoral program at Harvard School of Dental Medicine. In this innovative model, students conduct patient-based comprehensive care and complete assigned patient cases on which their performance is assessed, in contrast with a traditional model based on procedural numerical requirements. In our new model, senior tutors, who are full-time faculty members, act as group leaders responsible for patient assignment, treatment planning, monitoring of student performance, and verification of patient care. The number of completed patient cases in this new comprehensive care system increased from a previous average of 12.8 cases per student prior to graduation to 22.8 cases. Additionally, the number of patients who had to be transferred due to outstanding or pending treatment when their student provider graduated or because of students' need to fulfill discipline requirements has decreased from an average of 16.4 to 4.6. PMID- 22058390 TI - Testing the educational potential of 3D visualization software in oral radiographic interpretation. AB - There is heightened optimism about the potential of 3D visualization software as an alternative learning resource in radiology education. The purpose of this study was to investigate the effect of 3D visualization software on students' learning of oral radiographic interpretation from 2D radiographic images. Fourth year dental students underwent a learning intervention phase of radiographic interpretation of oral pathoses using 3D visualization software. The success of the educational intervention was assessed by quantitative means, using a radiographic interpretation test, and by qualitative means, using a structured Likert-scale survey, asking students to evaluate their own learning outcomes. It was anticipated that training with the rotational mode of 3D visualization software would provide additional depth cues, enabling students to create spatial mental models of anatomy that they can apply to 2D radiographic interpretation of oral pathoses. Although quantitative assessment did not support this, questionnaire evaluations demonstrated a positive effect of the 3D visualization software by enhancing students' learning about radiographic interpretation. Despite much optimism about the educational potential of 3D visualization software, it is important to understand the interactions between learners and such new technologies in order to identify potential advantages and limitations prior to embracing them as learning resources. PMID- 22058391 TI - An innovative HIV training program for dental students. AB - Dentists need to be able to give people with HIV/AIDS compassionate and comprehensive care. Previous studies have shown that many dental students have negative attitudes towards treating such individuals. This article addresses the effectiveness of a program that trains dental students in the issues of treating this population. All predoctoral students at the Loma Linda University School of Dentistry are required to receive this training. Students complete a pre-session survey during their third year and a post-session survey as they complete the training during their fourth year. The survey was administered from 2003 to 2009 during which 386 students completed responses to the post-session survey. Five questions in the survey address self-evaluation of knowledge, attitudes, and confidence in the efficacy of universal precautions and post-exposure prophylaxis following bloodborne exposures. This study reports on five two-year testing cycles and shows significant shifts in all five areas surveyed. The most significant gains were in the two areas that are not addressed in much detail in other courses in the dental school curriculum. These are familiarity with post exposure prophylaxis (PEP) and confidence in the efficacy of PEP. These data support the usefulness of such a program in preparing future dentists to deliver appropriate care to persons living with HIV/AIDS. PMID- 22058392 TI - Dental students' attitudes toward the design of a computer-based treatment planning tool. AB - The purpose of this study was to identify and evaluate the attitudes of a cohort of fourth- and fifth-year dental students (n=53) at Griffith University in Australia to a proposed computer-based Case Study and Treatment Planning (CSTP) tool. The tool would allow students to work through the process of comprehensive, multidisciplinary treatment planning for patients in a structured and logical manner. A questionnaire was designed to investigate the students' perceived needs, attitudes, and factors deemed to be important in the design of such a tool. Students responded on a seven-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). The survey was supplemented by two focus groups, one of fourth-year and one of fifth-year students. The survey results indicated strong agreement that there is a need for such a tool (fourth-year mean=6.24; fifth-year mean=5.75) and the likelihood that it would be used after hours and for extra treatment planning practice (fourth-year mean=5.82; fifth-year mean=5.45). The themes that emerged from the focus groups revealed students' agreement that a CSTP tool would be beneficial both for training and for faculty assessment of students' treatment planning skills. The type of concerns raised included whether a rigid treatment planning template might hamper the flexibility needed to deal with complex patient cases. Additionally, there was some concern that students' personal interaction with tutors would be reduced if this mode of computer-based treatment planning were to be used exclusively. In conclusion, the overall attitude of dental students was positive towards a CSTP tool. This study's findings provide guidance as to how such software could be developed and which features to include. PMID- 22058393 TI - Faculty impressions of dental students' performance with and without virtual reality simulation. AB - This study compared faculty perceptions and expectations of dental students' abilities using virtual reality simulation (VRS) to those who did not use virtual reality simulation (non-VRS) in an operative dentistry preclinical course. A sixteen-item survey with a ten-point rating scale and three open-ended questions asked about students' abilities in ergonomics, confidence level, performance, preparation, and self-assessment. The surveys were administered three times to a small group of preclinical faculty members. First, faculty members (n=12, 92 percent response rate) gave their perceptions of non-VRS students' abilities at the end of their traditional course. Secondly, faculty members (n=13, 100 percent response rate) gave their expectations of the next incoming class's abilities (VRS students) prior to the start of the course with traditional and VRS components. Finally, faculty members (n=13, 100 percent response rate) gave their perceptions of VRS students' abilities after completion of the course. A Tukey's test for multiple comparisons measured significance among survey items. Faculty perceptions of VRS students' abilities were higher than for non-VRS students for most abilities examined. However, the faculty members' expectations of VRS training were higher than their perceptions of the students' abilities after VRS training for most abilities examined. Since ergonomic development and technical performance were positively impacted by VRS training, these results support the use of VRS in a preclinical dental curriculum. PMID- 22058394 TI - Intraoral cameras as a computer-aided diagnosis tool for root canal orifices. AB - The aim of this study was to evaluate the diagnostic advantage of a new software tool in combination with an intraoral camera for automatic detection of root canal orifices in life videos via the access cavity of extracted human molars. The performance of a predoctoral dental student analyzing the images of the camera (without automatic detection) was compared with that of an experienced observer. Sensitivity and confidence intervals were provided and compared with histological slices of 200 teeth used for evaluation. The software's sensitivity for detection of root canal orifices was 0.957 (95 percent confidence interval: 0.936 to 0.972). The sensitivity for the observer was 0.906 (95 percent confidence interval: 0.877 to 0.929) compared to 0.847 (95 percent confidence interval: 0.813 to 0.877) achieved by the predoctoral student. The tested software reaches a high sensitivity for automatic real-time detection of root canal orifices with intraoral cameras in direct comparison to histological images. The system might be a useful help for both pre-and postdoctoral students as an aid for the detection of second mesiobuccal root canal orifices. PMID- 22058395 TI - A survey of U.S. dental school programs that help students consider academic careers. AB - The faculty shortage in dental education has been reported for many years and is expected to increase. Some dental schools have developed "grow your own" programs that introduce students to academic careers and give them teaching experiences. These programs generally consist of teaching assistant, fellowship, and peer tutoring opportunities. In this study, a nineteen-item survey was sent to fifty six U.S. dental schools to determine the extent to which such programs were being implemented. Thirty-six out of fifty-six dental schools responded, a response rate of 64 percent. Twenty-five schools or 69 percent of the respondents reported the existence of a formal teaching assistant, fellowship, or peer tutoring program in which students teach in some capacity. The main reasons reported for implementing these programs were to expose students to academia and to address faculty shortages. The respondents reported that positive outcomes for dental student teachers and their students were academic benefits and increased interest in academic life. Among the barriers reported were securing faculty and financial support and problems with scheduling. PMID- 22058396 TI - Beginning the socialization to a new workforce model: dental students' preliminary knowledge of and attitudes about the role of the dental therapist. AB - The purpose of the study reported here was to assess first- and second-year dental students' knowledge of and attitudes about the role of the dental therapist in the oral health care delivery system. The results of this study are informing the continued development and implementation of a new dental workforce training model at the University of Minnesota. Dental students at the university (Classes of 2012 and 2013) were surveyed in 2009, with follow-up surveys planned for the subsequent five years. Multiple-choice questions and statements to be ranked using a Likert scale were used to determine what the students knew and thought about dental therapists' scope of practice, care delivery, work quality, cost-effectiveness, and role in reducing disparities in oral health care access. The results suggest that the students had generally neutral or uncertain attitudes about dental therapy, based on minimal knowledge about the role of dental therapists. In addition, we found little difference in attitudes between the two classes, the only exception being that the first-year students less often perceived the therapists as a solution to access problems. These baseline data are guiding the intraprofessional training of dental, dental hygiene, and dental therapy students toward the goal of positive socialization to a new workforce model and affirmation of the dental therapist as a member of the oral health care team. PMID- 22058397 TI - Differences between ADEA Annual Session poster abstracts and their corresponding full published articles. AB - The purpose of this study was to investigate differences between abstracts of posters presented at the 79(th) (2002) and 80(th) (2003) Annual Session & Exhibition of the American Dental Education Association (ADEA) and the published full-length articles resulting from the same studies. The abstracts for poster presentation sessions were downloaded, and basic characteristics of the abstracts and their authors were determined. A PubMed search was then performed to identify the publication of full-length articles based on those abstracts in a peer reviewed journal. The differences between the abstract and the article were examined and categorized as major and minor differences. Differences identified included authorship, title, materials and methods, results, conclusions, and funding. Data were analyzed with both descriptive and analytic statistics. Overall, 89 percent of the abstracts had at least one variation from its corresponding article, and 65 percent and 76 percent of the abstracts had at least one major and minor variation, respectively, from its corresponding article. The most prevalent major variation was in study results, and the most prevalent minor variation was change in the number of authors. The discussion speculates on some possible reasons for these differences. PMID- 22058398 TI - The impact of service-learning on two groups of South African dental students. AB - Service-learning has become an important component in the education of medical and dental students around the world. Dental students at the University of Witwatersrand, South Africa, provide dental services to rural communities via the Phelophepa train or a Public Oral Health Facility (POHF). The Phelophepa train is a mobile primary health care facility offering dental, pharmacy, nursing, and medical services provided by health professions students. The objective of this study was to determine the impact this experience with service-learning has had on dental students. Final-year dental students in 2008 and 2009 participated in the study by completing a self-administered questionnaire. There was a 100 percent response rate (N=55) on the demographic questions and a 98 percent response rate (N=54) on the opinion questions. Students on the Phelophepa train performed more extractions and examinations than those at the POHFs. Most students (95 percent), both on the train and at the clinics, reported that their clinical skills and efficiency had improved, and 96 percent felt more aware of the communities' needs. Almost all the students (96 percent) reported that the experience had helped them define their personal strengths and weaknesses. Complaints they mentioned included large numbers of patients (87 percent), long working hours (60 percent), and equipment being inadequate (48 percent) or not working (40 percent). This program positively impacted these students and enhanced their personal growth and social responsibility by exposing them to the needs of rural and urban communities in South Africa. PMID- 22058399 TI - Attitudes of Iranian dental students toward their future careers: an exploratory study. AB - Students' attitudes toward and reasons for choosing careers are of great interest for educational systems around the world. The aims of this study were to investigate Iranian dental students' motivations in choosing dentistry as a career and their attitudes toward their future profession. A cross-sectional study of a group of 219 out of 225 (response rate: 97 percent) final-year dental students in four accredited dental schools in Tehran was conducted using a self administered, structured questionnaire. The data were analyzed using SPSS version 11.5 and the Mann-Whitney test. The most popular reasons for these students' choice of dentistry as a career were a general interest in medicine and desire to enter a prestigious profession with high social status. The majority of the students planned to enter private practice; fewer intended to pursue specialty education abroad. Most of the female students planned to work in a group practice environment such as a clinic rather than a solo practice. Single students showed greater enthusiasm than married ones for pursuing further studies abroad after graduation. Overall, these dental students appeared to have positive attitudes about the dental profession. PMID- 22058400 TI - Creating an effective PBL case in oral and maxillofacial surgery at a Chinese dental school: a dental education primer. AB - Problem-based learning (PBL) is a widely accepted educational method centered on the discussion and learning that emerge from a clinically based problem; however, little has been reported on the details of PBL case-writing in the dental education literature. This article outlines some principles of writing a PBL case as it is practiced at a Chinese dental school and presents, as an example, an actual case based on a clinical problem (ameloblastoma of the jaw) intended to provide a learning focus for predoctoral dental students. A good PBL case should allow for progressive, interdependent actions to be taken in the evaluation and overall management of the patient in context and should trigger inquiry and discussion among students in both the basic sciences (anatomy, physiology, biochemistry, pharmacology, pathophysiology, etc.) and related clinical sciences. The epidemiological, sociological, and ethical considerations related to each problem should also be emphasized as an essential component of effective health care provision. PMID- 22058401 TI - Effectiveness of a five-step method for teaching clinical skills to students in a dental college in India. AB - This study conducted at the PDM Dental College and Research Institute, Haryana, India, had the purpose of developing a teaching method based upon a five-step method for teaching clinical skills to students proposed by the American College of Surgeons. This five-step teaching method was used to place fissure sealants as an initial procedure by dental students in clinics. The sealant retention was used as an objective evaluation of the skill learnt by the students. The sealant retention was 92 percent at six- and twelve-month evaluations and 90 percent at the eighteen-month evaluation. These results indicate that simple methods can be devised for teaching clinical skills and achieve high success rates in clinical procedures requiring multiple steps. PMID- 22058402 TI - Greece's high dentist to population ratio: comparisons, causes, and effects. AB - Reaching the optimal dentist to population ratio is a common health policy challenge around the world, but while many countries have too few dentists for their populations, Greece is facing the opposite problem. This study was designed to describe and analyze trends in the number and distribution of dentists in Greece over the last thirty years and compare the Greek dentist to population ratio with that of the other twenty-six European Union (EU) countries. Demographic data for Greece were obtained from the Hellenic Dental Association and the National Statistical Service of Greece and were analyzed using nonparametric statistical tests. Data for the other EU countries were derived from various authoritative sources. In Greece, the number of dentists per 10,000 inhabitants increased significantly (p<0.05) from 1982 (7.7) to 2007 (13.0), ranking Greece first (in 2008) among the EU countries. The proportional increase in the number of dentists during the decade 1979-88 (30.4 percent) was significant (p<0.05), compared to the decade 1989-98 (22.3 percent) and the nine year period 1999-2007 (23.6 percent). In 1982 and 1992, the majority of dentists practiced in the Attica Prefecture (Athens) (55.2 percent and 52.6 percent, respectively), but this situation changed significantly in 2007 (p<0.05) (40.1 percent for Attica). The percentage of female dentists remained almost the same from 1982 until 2007, but female dentists' location of practice changed significantly (p<0.05) between 1992 and 2007. After reporting the data, we examine some of the reasons for and effects of the situation and consider the problem that, even with a high dentist to population ratio, Greece has significant oral health access problems. PMID- 22058403 TI - The single functional blast resistance gene Pi54 activates a complex defence mechanism in rice. AB - The Pi54 gene (Pi-k(h)) confers a high degree of resistance to diverse strains of the fungus Magnaporthe oryzae. In order to understand the genome-wide co expression of genes in the transgenic rice plant Taipei 309 (TP) containing the Pi54 gene, microarray analysis was performed at 72 h post-inoculation of the M. oryzae strain PLP-1. A total of 1154 differentially expressing genes were identified in TP-Pi54 plants. Of these, 587 were up-regulated, whereas 567 genes were found to be down-regulated. 107 genes were found that were exclusively up regulated and 58 genes that were down- regulated in the case of TP-Pi54. Various defence response genes, such as callose, laccase, PAL, and peroxidase, and genes related to transcription factors like NAC6, Dof zinc finger, MAD box, bZIP, and WRKY were found to be up-regulated in the transgenic line. The enzymatic activities of six plant defence response enzymes, such as peroxidase, polyphenol oxidase, phenylalanine ammonia lyase, beta-glucosidase, beta-1,3-glucanase, and chitinase, were found to be significantly high in TP-Pi54 at different stages of inoculation by M. oryzae. The total phenol content also increased significantly in resistant transgenic plants after pathogen inoculation. This study suggests the activation of defence response and transcription factor-related genes and a higher expression of key enzymes involved in the defence response pathway in the rice line TP-Pi54, thus leading to incompatible host-pathogen interaction. PMID- 22058404 TI - Early agricultural pathways: moving outside the 'core area' hypothesis in Southwest Asia. AB - The origins of agriculture in the Near East has been associated with a 'core area', located in south-eastern Turkey, in which all major crops were brought into domestication within the same local domestication system operated by a single cultural group. Such an origin leads to a scenario of rapid invention of agriculture by a select cultural group and typically monophyletic origins for most crops. Surprisingly, support for a core area has never been directly tested with archaeological evidence. Over the past decade a large amount of new archaeological and genetic evidence has been discovered which brings new light on the origins of agriculture. In this review, this new evidence was brought together in order to evaluate whether a core region of origin is supported. Evidence shows that origins began earlier than previously assumed, and included 'false starts' and dead ends that involved many more species than the typical eight founder crops associated with the core area. The rates at which domestication syndrome traits became fixed were generally slow, rather than rapid, and occurred over a geographically wide range that included the North and South Levant as well as the core area. Finally, a survey of the estimated ages of archaeological sites and the onset of domestication indicates that the domestication process was ongoing in parallel outside of the core area earlier than within it. Overall, evidence suggests a scenario in which crops were domesticated slowly in different locations around the Near East rather than emanating from a core area. PMID- 22058405 TI - Metabolism control over growth: a case for trehalose-6-phosphate in plants. AB - How plants relate their requirements for energy with the reducing power necessary to fuel growth is not understood. The activated glucose forms and NADPH are key precursors in pathways yielding, respectively, energy and reducing power for anabolic metabolism. Moreover, they are substrates or allosteric regulators of trehalose-phosphate synthase (TPS1) in fungi and probably also in plants. TPS1 synthesizes the signalling metabolite trehalose-6-phosphate (T6P) and, therefore, has the potential to relate reducing power with energy metabolism to fuel growth. A working model is discussed where trehalose-6-phosphate (T6P) inhibition of SnRK1 is part of a growth-regulating loop in young and metabolically active heterotrophic plant tissues. SnRK1 is the Snf1 Related Kinase 1 and the plant homologue of the AMP-dependent protein kinase of animals, a central energy gauge. T6P accumulation in response to high sucrose levels in a cell inhibits SnRK1 activity, thus promoting anabolic processes and growth. When T6P levels drop due to low glucose-6-phosphate, uridine-diphosphoglucose, and altered NADPH or due to restricted TPS1 activity, active SnRK1 promotes catabolic processes required to respond to energy and carbon deprivation. The model explains why too little or too much T6P has been found to be growth inhibitory: Arabidopsis thaliana embryos and seedlings without TPS1 are growth arrested and Arabidopsis seedlings accumulating T6P on a trehalose medium are growth arrested. Finally, the insight gained with respect to the possible role of T6P metabolism, where it is known to alter developmental and environmental responses of plants, is discussed. PMID- 22058406 TI - In Posidonia oceanica cadmium induces changes in DNA methylation and chromatin patterning. AB - In mammals, cadmium is widely considered as a non-genotoxic carcinogen acting through a methylation-dependent epigenetic mechanism. Here, the effects of Cd treatment on the DNA methylation patten are examined together with its effect on chromatin reconfiguration in Posidonia oceanica. DNA methylation level and pattern were analysed in actively growing organs, under short- (6 h) and long- (2 d or 4 d) term and low (10 MUM) and high (50 MUM) doses of Cd, through a Methylation-Sensitive Amplification Polymorphism technique and an immunocytological approach, respectively. The expression of one member of the CHROMOMETHYLASE (CMT) family, a DNA methyltransferase, was also assessed by qRT PCR. Nuclear chromatin ultrastructure was investigated by transmission electron microscopy. Cd treatment induced a DNA hypermethylation, as well as an up regulation of CMT, indicating that de novo methylation did indeed occur. Moreover, a high dose of Cd led to a progressive heterochromatinization of interphase nuclei and apoptotic figures were also observed after long-term treatment. The data demonstrate that Cd perturbs the DNA methylation status through the involvement of a specific methyltransferase. Such changes are linked to nuclear chromatin reconfiguration likely to establish a new balance of expressed/repressed chromatin. Overall, the data show an epigenetic basis to the mechanism underlying Cd toxicity in plants. PMID- 22058407 TI - Induction of root Fe(lll) reductase activity and proton extrusion by iron deficiency is mediated by auxin-based systemic signalling in Malus xiaojinensis. AB - Iron is a critical cofactor for a number of metalloenzymes involved in respiration and photosynthesis, but plants often suffer from iron deficiency due to limited supplies of soluble iron in the soil. Iron deficiency induces a series of adaptive responses in various plant species, but the mechanisms by which they are triggered remain largely unknown. Using pH imaging and hormone localization techniques, it has been demonstrated here that root Fe(III) reductase activity and proton extrusion upon iron deficiency are up-regulated by systemic auxin signalling in a Fe-efficient woody plant, Malus xiaojinensis. Split-root experiments demonstrated that Fe-deprivation in a portion of the root system induced a dramatic increase in Fe(III) reductase activity and proton extrusion in the Fe-supplied portion, suggesting that the iron deficiency responses were mediated by a systemic signalling. Reciprocal grafting experiments of M. xiaojinensis with Malus baccata, a plant with no capability to produce the corresponding responses, indicate that the initiation of the systemic signalling is likely to be determined by roots rather than shoots. Iron deficiency induced a substantial increase in the IAA content in the shoot apex and supplying exogenous IAA analogues (NAA) to the shoot apex could mimic the iron deficiency to trigger the corresponding responses. Conversely, preventing IAA transport from shoot to roots blocked the iron deficiency responses. These results strongly indicate that the iron deficiency-induced physiological responses are mediated by systemic auxin signalling. PMID- 22058408 TI - Low-temperature-modulated fruit ripening is independent of ethylene in 'Sanuki Gold' kiwifruit. AB - Fruit ripening in response to treatments with propylene, 1-methycyclopropene (1 MCP), and low temperature was characterized in 'Sanuki Gold' kiwifruit, Actinidia chinensis Planch. Propylene treatment immediately induced rapid fruit softening, increased AC-PG (polygalacturonase) and AC-EXP (expansin) mRNA accumulation, and stimulated an increase in the soluble solid concentration (SSC) and a decrease in titratable acidity (TA). After 3 d exposure to propylene, ethylene production and AC-PL (pectate lyase) mRNA accumulation were observed. 1-MCP treatment after 24 h exposure to propylene eliminated AC-PG mRNA accumulation and suppressed continued changes in SSC and TA. Application of 1-MCP at the start of the treatment, followed by continuous propylene exposure, markedly delayed fruit softening, and the expression of the cell wall-modifying genes, and changes in the SSC and TA, indicating that kiwifruit become insensitive to ethylene at least for 3 d following 1-MCP exposure. Surprisingly, significant fruit softening, mRNA accumulation of AC-PG, AC-PL, and AC-EXP, and decreased TA were observed without ethylene production in intact fruit stored at low temperature for 1 month, but not in fruit stored at room temperature. Repeated 1-MCP treatments (twice a week) failed to inhibit the changes that occurred in low temperature storage. These observations indicate that low temperature modulates the ripening of kiwifruit in an ethylene-independent manner, suggesting that kiwifruit ripening is inducible by either ethylene or low temperature signals. PMID- 22058409 TI - Biogeography in a continental island: population structure of the relict endemic centipede Craterostigmus tasmanianus (Chilopoda, Craterostigmomorpha) in Tasmania using 16S rRNA and COI. AB - We used 16S ribosomal RNA (rRNA) and cytochrome c oxidase subunit I (COI) sequence data to investigate the population structure in the centipede Craterostigmus tasmanianus Pocock, 1902 (Chilopoda: Craterostigmomorpha: Craterostigmidae) and to look for possible barriers to gene flow on the island of Tasmania, where C. tasmanianus is a widespread endemic. We first confirmed a molecular diagnostic character in 28S rRNA separating Tasmanian Craterostigmus from its sister species Craterostigmus crabilli (Edgecombe and Giribet 2008) in New Zealand and found no shared polymorphism in this marker for the 2 species. In Tasmania, analysis of molecular variance analysis showed little variation at the 16S rRNA and COI loci within populations (6% and 13%, respectively), but substantial variation (56% and 48%, respectively) among populations divided geographically into groups. We found no clear evidence of isolation by distance using a Mantel test. Bayesian clustering and gene network analysis both group the C. tasmanianus populations in patterns which are broadly concordant with previously known biogeographical divisions within Tasmania, but we did not find that genetic distance varied in a simple way across cluster boundaries. The coarse-scale geographical sampling on which this study was based should be followed in the future by sampling at a finer spatial scale and to investigate genetic structure within clusters and across cluster boundaries. PMID- 22058410 TI - First analysis of multiple paternity in an oviparous shark, the small-spotted catshark (Scyliorhinus canicula L.). AB - Multiple paternity (MP) has been demonstrated in a variety of sharks, although its prevalence and the number of sires per litter vary considerably among species. To date, such analyses have focused on viviparous species that possess only part of the wide spectrum of reproductive strategies developed in elasmobranchs. We analyzed MP in an oviparous species, the small-spotted catshark (Scyliorhinus canicula). In total, 150 neonates originating from 13 different mothers were genotyped using 12 microsatellite loci. MP was commonplace, with progeny from 92% of females sired by multiple males. This result is consistent with the reproductive biology of the species, particularly its protracted breeding season and potential for long-term sperm storage. The significance of these findings is discussed in light of small-spotted catshark behavior, which suggests that the cost of avoiding mating attempts initiated by males may be high and is therefore supportive of convenience polyandry as an explanation for MP. Eggs were followed from the time they were laid to when they hatched, offering a rare opportunity to investigate juvenile development in more detail. PMID- 22058411 TI - Escape from CD8+ T cell response by natural variants of an immunodominant epitope from Theileria parva is predominantly due to loss of TCR recognition. AB - Polymorphism of immunodominant CD8(+) T cell epitopes can facilitate escape from immune recognition of pathogens, leading to strain-specific immunity. In this study, we examined the TCR beta-chain (TRB) diversity of the CD8(+) T cell responses of cattle against two immunodominant epitopes from Theileria parva (Tp1(214-224) and Tp2(49-59)) and investigated the role of TCR recognition and MHC binding in determining differential recognition of a series of natural variants of the highly polymorphic Tp2(49-59) epitope by CD8(+) T cell clones of defined TRB genotype. Our results show that both Tp1(214-224) and Tp2(49-59) elicited CD8(+) T cell responses using diverse TRB repertoires that showed a high level of stability following repeated pathogenic challenge over a 3-y period. Analysis of single-alanine substituted versions of the Tp2(49-59) peptide demonstrated that Tp2(49-59)-specific clonotypes had a broad range of fine specificities for the epitope. Despite this diversity, all natural variants exhibited partial or total escape from immune recognition, which was predominantly due to abrogation of TCR recognition, with mutation resulting in loss of the lysine residue at P8, playing a particularly dominant role in escape. The levels of heterozygosity in individual Tp2(49-59) residues correlated closely with loss of immune recognition, suggesting that immune selection has contributed to epitope polymorphism. PMID- 22058412 TI - Inflammasome activation of IL-18 results in endothelial progenitor cell dysfunction in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous manifestations including severe organ damage and vascular dysfunction leading to premature atherosclerosis. IFN-alpha has been proposed to have an important role in the development of lupus and lupus-related cardiovascular disease, partly by repression of IL-1 pathways leading to impairments in vascular repair induced by endothelial progenitor cells (EPCs) and circulating angiogenic cells (CACs). Counterintuitively, SLE patients also display transcriptional upregulation of the IL-1beta/IL-18 processing machinery, the inflammasome. To understand this dichotomy and its impact on SLE-related cardiovascular disease, we examined cultures of human and murine control or lupus EPC/CACs to determine the role of the inflammasome in endothelial differentiation. We show that caspase-1 inhibition improves dysfunctional SLE EPC/CAC differentiation into mature endothelial cells and blocks IFN-alpha-mediated repression of this differentiation, implicating inflammasome activation as a crucial downstream pathway leading to aberrant vasculogenesis. Furthermore, serum IL-18 levels are elevated in SLE and correlate with EPC/CAC dysfunction. Exogenous IL-18 inhibits endothelial differentiation in control EPC/CACs and neutralization of IL-18 in SLE EPC/CAC cultures restores their capacity to differentiate into mature endothelial cells, supporting a deleterious effect of IL-18 on vascular repair in vivo. Upregulation of the inflammasome machinery was operational in vivo, as evidenced by gene array analysis of lupus nephritis biopsies. Thus, the effects of IFN-alpha are complex and contribute to an elevated risk of cardiovascular disease by suppression of IL-1beta pathways and by upregulation of the inflammasome machinery and potentiation of IL-18 activation. PMID- 22058413 TI - C5a regulates NKT and NK cell functions in sepsis. AB - Complement, NKT, and NK cells play critical roles in the first line defense against pathogens. Functional roles for both C5a receptors, that is, complement receptor C5a (C5aR) and C5a receptor-like 2 (C5L2), in sepsis have been demonstrated. However, the role of C5a in innate lymphocyte activation during sepsis remains elusive. In this article, we show that naive NKT and NK cells already express high levels of C5aR and minor levels of C5L2 mRNA, but no protein. Upon Escherichia coli-induced sepsis, we found C5aR surface expression on subpopulations of NKT and NK cells, suggesting rapid translation into C5aR protein on bacterial encounter. Importantly, significantly increased survival in the absence of C5aR, NKT, and NK cells, but not of C5L2, was associated with reduced IFN-gamma and TNF-alpha serum levels. Sepsis induction in C5aR(+)/C5aR(-) mixed bone marrow chimeras identified cognate engagement of C5aR on NKT cells as an important factor for the recruitment of NKT cells. Furthermore, we found synergistic interaction between C5aR and TLRs enhancing the production of TNF alpha and IFN-gamma from NKT and NK cells in cocultures with dendritic cells. Our results identify C5aR activation as a novel pathway driving detrimental effects of NKT and NK cells during early experimental sepsis. PMID- 22058414 TI - Pathogenic and protective functions of TNF in neuroinflammation are defined by its expression in T lymphocytes and myeloid cells. AB - TNF displays pathogenic activities in many autoimmune disorders. However, anti TNF therapy in multiple sclerosis patients failed because of poorly understood reasons. We used a panel of gene-targeted mice that allowed cell-type specific ablation of TNF to uncover pathogenic and protective contributions of this cytokine during autoimmune disease of the CNS. T cells and myeloid cells were found to be critical cellular sources of TNF during experimental autoimmune encephalomyelitis (EAE). TNF produced by myeloid cells accelerated the onset of disease by regulation of chemokine expression in the CNS, driving the recruitment of inflammatory cells into the target organ. TNF produced by T cells exacerbated the damage to the CNS during EAE by regulating infiltration of inflammatory myeloid cells into the CNS. In secondary lymphoid organs, TNF expressed by myeloid cells and T cells acted in synergy to dampen IL-12p40 and IL-6 production by APCs, subsequently inhibiting the development of encephalitogenic T cell responses of Th1 and Th17 types. This dual role of TNF during EAE (protective in lymphoid organs and pathogenic in CNS) suggests that global TNF blockade might be inefficient in multiple sclerosis patients because augmented autoreactive T cell development in lymphoid tissues might overwhelm the beneficial effects resulting from TNF inhibition in the CNS. PMID- 22058415 TI - Uric acid-driven Th17 differentiation requires inflammasome-derived IL-1 and IL 18. AB - Uric acid is released from damaged cells and serves as a danger signal that alerts the immune system to potential threats, even in the absence of microbial infection. Uric acid modulation of innate immune responses has been extensively studied, but the impact of this damage-associated molecular pattern on adaptive responses remains largely unknown. In this study, we report that, in the presence of NF-kappaB signaling, uric acid crystals were capable of stimulating dendritic cells to promote the release of cytokines associated with Th17 polarization. Accordingly, naive CD4(+) T cells cocultured with uric acid-treated dendritic cells differentiated toward the Th17 lineage. Th17 differentiation required the inflammasome-dependent cytokines IL-1alpha/beta and IL-18 in both in vitro and in vivo models, and the inflammasome adaptor protein ASC and caspase-1 were essential for Th17 responses. Collectively, our findings indicate a novel role for the danger signal uric acid, in cooperation with NF-kappaB activation, in driving proinflammatory Th17 differentiation. Our data indicate that sterile inflammation shapes adaptive immunity, in addition to influencing early innate responses. PMID- 22058416 TI - Regulation of IFN-lambda1 promoter activity (IFN-lambda1/IL-29) in human airway epithelial cells. AB - The type III (lambda) IFNs (IFN-lambda1, IFN-lambda2, and IFN-lambda3) and their receptor are the most recently discovered IFN family. They are induced by viruses and mediate antiviral activity, but type III IFNs have an important, specific functional niche at the immune/epithelial interface, as well as in the regulation of Th2 cytokines. Their expression appears diminished in bronchial epithelial cells of rhinovirus-infected asthmatic individuals. We investigated the regulation of IFN-lambda1 expression in human airway epithelial cells using reporter genes analysis, chromatin immunoprecipitation, small interfering RNA knockdown, and DNase footprinting. In this article, we define the c-REL/p65 NF kappaB heterodimer and IRF-1 as key transcriptional activators and ZEB1, B lymphocyte-induced maturation protein 1, and the p50 NF-kappaB homodimer as key repressors of the IFN-lambda1 gene. We further show that ZEB1 selectively regulates type III IFNs. To our knowledge, this study presents the first characterization of any type III IFN promoter in its native context and conformation in epithelial cells and can now be applied to understanding pathogenic dysregulation of IFN-lambda1 in human disease. PMID- 22058417 TI - Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. AB - We identify in this article a new class of lung tissue-resident memory CD4 T cells that exhibit tissue tropism and retention independent of Ag or inflammation. Tissue-resident memory CD4 T cells in the lung did not circulate or emigrate from the lung in parabiosis experiments, were protected from in vivo Ab labeling, and expressed elevated levels of CD69 and CD11a compared with those of circulating memory populations. Importantly, influenza-specific lung-resident memory CD4 T cells served as in situ protectors to respiratory viral challenge, mediating enhanced viral clearance and survival to lethal influenza infection. By contrast, memory CD4 T cells isolated from spleen recirculated among multiple tissues without retention and failed to mediate protection to influenza infection, despite their ability to expand and migrate to the lung. Our results reveal tissue compartmentalization as a major determining factor for immune mediated protection in a key mucosal site, important for targeting local protective responses in vaccines and immunotherapies. PMID- 22058418 TI - Multiple human papillomavirus infections and type competition in men. AB - BACKGROUND: There is little information on multiple human papillomavirus (HPV) infections and the potential for type competition in men, yet competition may impact the type-specific efficacy of HPV vaccination. METHODS: Among 2702 uncircumcised men in Kisumu, Kenya, who were seronegative for human immunodeficiency virus, the observed numbers of HPV types detected were compared with the expected number, which was simulated under the assumption of independent infections. To assess the potential for HPV type competition, adjusted odds ratios for pairwise combinations of prevalent HPV type infections were estimated using semi-Bayesian methods. RESULTS: Half of all men were HPV positive, of whom 57% had multiple HPV types. We observed men without HPV infection and with >=4 HPV types more often than expected if infections were independent. No negative associations between individual HPV types were observed. HPV types 31, 39, 56, 58, and 59 were positively associated with both carcinogenic vaccine types HPV-16 and HPV-18 (2-sided P value <.05). CONCLUSIONS: Men who were HPV infected were likely to test positive for >1 HPV type. Cross-sectional associations between individual HPV types were positive and did not appear to be type-specific. Thus, we did not identify HPV types that are candidates for potential HPV type competition in men. PMID- 22058419 TI - Erlotinib for pretreated squamous cell carcinoma of the lung in Japanese patients. AB - OBJECTIVE: Erlotinib has demonstrated survival benefit in patients with not only adenocarcinoma but also squamous cell carcinoma. Epidermal growth factor receptor tyrosine kinase inhibitors are more effective in Asian populations, including the Japanese than in western populations. However, a higher incidence of interstitial lung disease has been reported as a fatal adverse event in the Japanese population. There is little data on erlotinib for Japanese patients with pretreated squamous cell carcinoma. METHODS: Between January 2004 and October 2010, we retrospectively evaluated the efficacy and toxicity of erlotinib administered as the first epidermal growth factor receptor-tyrosine kinase inhibitors for 41 Japanese patients with pretreated squamous cell carcinoma. Patients with pre-existing interstitial lung disease were carefully excluded by several examinations including high-resolution computed tomography. RESULTS: The response rate and disease control rate were 9.7% [95% confidence interval: 2.7 23.1%) and 43.9% (95% confidence interval: 28.5-60.2%], respectively. Median time to treatment failure and overall survival were 2.2 months (95% confidence interval: 1.0-2.8 months) and 11.0 months (95% confidence interval: 5.7-15.7 months), respectively. Interstitial lung disease (Grade 5) was observed in one (2.4%) patient. Patients with Grade 0-1 skin rashes vs. patients with Grades 2-3 exhibited disease control rates of 28 vs. 83% (P = 0.0017), and median time to treatment failure of 1.2 months vs. 3.4 months (P = 0.0099). CONCLUSIONS: Erlotinib has moderate efficacy for pretreated squamous cell carcinoma in Japanese patients. A higher grade of skin rash was associated with clinical benefit. Careful exclusion of pre-existing interstitial lung disease can minimize the occurrence of interstitial lung disease. PMID- 22058420 TI - Pivotal advance: peritoneal cavity B-1 B cells have phagocytic and microbicidal capacities and present phagocytosed antigen to CD4+ T cells. AB - Breaking the long-held paradigm that primary B cells are not phagocytic, several studies have demonstrated recently that B cells from fish, amphibians, and reptilians have a significant phagocytic capacity. Whether such capacity has remained conserved in certain mammalian B cell subsets is presently an enigma. Here, we report a previously unrecognized ability of PerC B-1a and B-1b lymphocytes to phagocytose latex beads and bacteria. In contrast, B-2 lymphocytes had an almost negligible ability to internalize these particles. Upon phagocytosis, B-1a and B-1b cells were able to mature their phagosomes into phagolysosomes and displayed the ability to kill internalized bacteria. Importantly, B-1a and B-1b cells effectively present antigen recovered from phagocytosed particles to CD4(+) T cells. However, these cells showed a much lower competence to present soluble antigen or antigen from large, noninternalized particles. B-1 B cells presented particulate and soluble antigen to CD4(+) T cells more efficiently than macrophages, whereas DCs were the most potent APCs. The novel phagocytic and microbicidal abilities identified in B-1 B lymphocytes strengthen the innate nature that has long been attributed to these cells. In the context of adaptive immunity, we show that these innate immune processes are relevant, as they enable B-1 B cells to present phagocytosable particulate antigen. These capacities position these cells at the crossroads that link innate with adaptive immune processes. In a broader context, these newly identified capacities of B-1 B cells further support the previously recognized functional, developmental, and evolutionary relationships between these cells and macrophages. PMID- 22058421 TI - Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation. AB - Chemoattractants are pivotal mediators of host defense, orchestrating the recruitment of immune cells into sites of infection and inflammation. Chemoattractants display vast chemical diversity and include bioactive lipids, proteolytic fragments of serum proteins, and chemokines (chemotactic cytokines). All chemoattractants induce chemotaxis by activating seven-transmembrane-spanning GPCRs expressed on immune cells, establishing the concept that all chemoattractants are related in function. However, although chemoattractants have overlapping functions in vitro, recent in vivo data have revealed that they function, in many cases, nonredundantly in vivo. The chemically diverse nature of chemoattractants contributes to the fine control of leukocyte trafficking in vivo, with sequential chemoattractant use guiding immune cell recruitment into inflammatory sites. Lipid mediators frequently function as initiators of leukocyte recruitment, attracting the first immune cells into tissues. These initial responding immune cells produce cytokines locally, which in turn, induce the local release of chemokines. Local chemokine production then markedly amplifies subsequent waves of leukocyte recruitment. These new discoveries establish a paradigm for leukocyte recruitment in inflammation--described as lipid-cytokine-chemokine cascades--as a driving force in the effector phase of immune responses. PMID- 22058422 TI - TLR9 and TLR7 agonists mediate distinct type I IFN responses in humans and nonhuman primates in vitro and in vivo. AB - Human I-IFNs include IFN-beta and 13 independently regulated subtypes of IFN alpha (I-IFNs). TLR7 and -9 induce I-IFNs, but it is unknown whether their subtype repertoire is similar. This study used new PCR arrays that selectively amplify individual I-IFN subtype genes of human and nonhuman primates to characterize the TLR7- and -9-mediated IFN response in vitro and in vivo. We show that in human PBMCs, TLR7 agonists induce a rapid burst of I-IFN transcripts, consisting primarily of IFN-alpha1/13, -alpha2, and -alpha14. In contrast, TLR9 agonists, regardless of the type used (CpG C-, B-, or D-ODN), prompted slower but sustained expression of IFN-alpha1/13, -alpha2, -alpha7, -alpha8, -alpha10, alpha14, -alpha16, and -alpha21. These qualitative differences were translated downstream as differences in the pattern of IFN-inducible genes. In macaque PBMCs, imiquimod produced a short burst of IFN mRNA, dominated by IFN-alpha8, whereas C- or D-ODN induced a greater than tenfold increase in transcripts for all I-IFN subtypes by 12 h of culture. Differences were more evident in vivo, where TLR7 and -9 agonists induced significantly different levels of I-IFN transcripts in skin. Although the rates of gene transcription differed significantly for individual TLR9 agonists, their IFN-alpha subtype signature was almost identical, indicating that the type of receptor dictates the quality of the I-IFN response in vitro and in vivo. These results may underlie the differential therapeutic effects of TLR7 and -9 agonists and should inform future clinical studies. PMID- 22058423 TI - Pivotal advance: characterization of mouse liver phagocytic B cells in innate immunity. AB - Although B cells in vertebrates have been thought to lack phagocytic activity, there has been a recent report of such ability by the B cells of early vertebrates such as fish and frogs. Here, we show for the first time that mouse liver IgM(+) B cells actively phagocytose microsphere beads and Escherichia coli and that they effectively kill bacterial cells. Such phagocytic activity is not observed in other liver MNCs, except for F4/80(+) Kupffer cells. In the presence of fresh mouse serum (but not heat-inactivated serum), the heat-killed E. coli phagocytic activity of liver B cells increased significantly but was inhibited significantly by anticomplement component C3 antibody, suggesting E. coli opsonization by serum factors, including complement components. Upon i.v. injection of FITC-labeled E. coli into mice, a substantial proportion of liver B cells phagocytosed the bacteria, as compared with spleen B cells. Functional phagolysosome formation in liver B cells was supported by several reagents showing an acidic change and lysosomes in the phagocytosed vacuoles. Indeed, mouse liver B cells killed viable E. coli more efficiently than did spleen B cells in vitro. Further, E. coli-phagocytic liver B cells produced a substantial amount of IL-12. These results indicate that liver B cells have phagocytic and bactericidal activities similar to those of dedicated phagocytes and may contribute to bacterial clearance. PMID- 22058424 TI - Murine bone marrow-derived macrophages differentiated with GM-CSF become foam cells by PI3Kgamma-dependent fluid-phase pinocytosis of native LDL. AB - Accumulation of cholesterol by macrophage uptake of LDL is a key event in the formation of atherosclerotic plaques. Previous research has shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) is present in atherosclerotic plaques and promotes aortic lipid accumulation. However, it has not been determined whether murine GM-CSF-differentiated macrophages take up LDL to become foam cells. GM-CSF-differentiated macrophages from LDL receptor-null mice were incubated with LDL, resulting in massive macrophage cholesterol accumulation. Incubation of LDL receptor-null or wild-type macrophages with increasing concentrations of 125I-LDL showed nonsaturable macrophage LDL uptake that was linearly related to the amount of LDL added, indicating that LDL uptake was mediated by fluid-phase pinocytosis. Previous studies suggest that phosphoinositide 3-kinases (PI3K) mediate macrophage fluid-phase pinocytosis, although the isoform mediating this process has not been determined. Because PI3Kgamma is known to promote aortic lipid accumulation, we investigated its role in mediating macrophage fluid-phase pinocytosis of LDL. Wild-type macrophages incubated with LDL and the PI3Kgamma inhibitor AS605240 or PI3Kgamma-null macrophages incubated with LDL showed an ~50% reduction in LDL uptake and cholesterol accumulation compared with wild-type macrophages incubated with LDL only. These results show that GM-CSF-differentiated murine macrophages become foam cells by fluid-phase pinocytosis of LDL and identify PI3Kgamma as contributing to this process. PMID- 22058425 TI - Structural characterization of wax esters by electron ionization mass spectrometry. AB - The interpretation of the electron ionization mass spectra of straight-chain and methyl-branched saturated and unsaturated wax esters (WEs) is discussed in this study based on the spectra of 154 standards. The most important fragments indicative of the structure of the acid and alcohol chains are identified and summarized for WEs with various number of double bonds in the chains. Briefly, most WEs provide acylium ions allowing structural characterization of the acid part, whereas the alcohol part gives corresponding alkyl radical cations. The elemental composition of selected important fragments is established from a high resolution accurate mass analysis. The ion abundances are discussed with respect to the length and unsaturation of the aliphatic chains. The interpretation of the spectra of branched or unsaturated WEs requires the recognition of small but important peaks that are difficult to discern among the other fragments. We demonstrate that such fragments are easily detected in differential mass spectra. This approach requires spectra of WE standards (e.g., straight-chain analogs in the case of branched WEs) recorded under the same experimental conditions. The WEs mass spectral database provided in the supplemental data can be used as a reference for the analysis of the GC/EI-MS data. PMID- 22058426 TI - Property-based design of a glucosylceramide synthase inhibitor that reduces glucosylceramide in the brain. AB - Synthesis inhibition is the basis for the treatment of type 1 Gaucher disease by the glucosylceramide synthase (GCS) inhibitor eliglustat tartrate. However, the extended use of eliglustat and related compounds for the treatment of glycosphingolipid storage diseases with CNS manifestations is limited by the lack of brain penetration of this drug. Property modeling around the D-threo-1-phenyl 2-decanoylamino-3-morpholino-propanol (PDMP) pharmacophore was employed in a search for compounds of comparable activity against the GCS but lacking P glycoprotein (MDR1) recognition. Modifications of the carboxamide N-acyl group were made to lower total polar surface area and rotatable bond number. Compounds were screened for inhibition of GCS in crude enzyme and whole cell assays and for MDR1 substrate recognition. One analog, 2-(2,3-dihydro-1H-inden-2-yl)-N-((1R,2R) 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-hydroxy-3-(pyrrolidin-1-yl)propan-2 yl)acetamide (CCG-203586), was identified that inhibited GCS at low nanomolar concentrations with little to no apparent recognition by MDR1. Intraperitoneal administration of this compound to mice for 3 days resulted in a significant dose dependent decrease in brain glucosylceramide content, an effect not seen in mice dosed in parallel with eliglustat tartrate. PMID- 22058427 TI - Relationship of glucose and oleate metabolism to cardiac function in lipin-1 deficient (fld) mice. AB - Lipin-1 is the major phosphatidate phosphatase (PAP) in the heart and a transcriptional coactivator that regulates fatty acid (FA) oxidation in the liver. As the control of FA metabolism is essential for maintaining cardiac function, we investigated whether lipin-1 deficiency affects cardiac metabolism and performance. Cardiac PAP activity in lipin-1 deficient [fatty liver dystrophy (fld)] mice was decreased by >80% compared with controls. Surprisingly, oleate oxidation and incorporation in triacylglycerol (TG), as well as glucose oxidation, were not significantly different in perfused working fld hearts. Despite this, [3H]oleate accumulation in phosphatidate and phosphatidylinositol was increased in fld hearts, reflecting the decreased PAP activity. Phosphatidate accumulation was linked to increased cardiac mammalian target of rapamycin complex 1 (mTORC1) signaling and endoplasmic reticulum (ER) stress. Transthoracic echocardiography showed decreased cardiac function in fld mice; however, cardiac dysfunction was not observed in ex vivo perfused working fld hearts. This showed that changes in systemic factors due to the global absence of lipin-1 could contribute to the decreased cardiac function in vivo. Collectively, this study shows that fld hearts exhibit unchanged oleate esterification, as well as oleate and glucose oxidation, despite the absence of lipin-1. However, lipin-1 deficiency increases the accumulation of newly synthesized phosphatidate and induces aberrant cell signaling. PMID- 22058428 TI - CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women. AB - BACKGROUND: Mutations in the CHEK2 gene confer a moderately increased breast cancer risk. The risk for female carriers of the CHEK2*1100delC mutation is twofold increased. Breast cancer risk for carrier women is higher in a familial breast cancer setting which is due to coinheritance of additional genetic risk factors. This study investigated the occurrence of homozygosity for the CHEK2*1100delC allele among familial breast cancer cases and the associated breast cancer risk. METHODS AND RESULTS: Homozygosity for the CHEK2*1100delC allele was identified in 8/2554 Dutch independent familial non-BRCA1/2 breast cancer cases. The genotype relative risk for breast cancer of homozygous and heterozygous familial breast cancer cases was 101.34 (95% CI 4.47 to 121 000) and 4.04 (95% CI 0.88 to 21.0), respectively. Female homozygotes appeared to have a greater than twofold increased breast cancer risk compared to familial CHEK2*1100delC heterozygotes (p=0.044). These results and the occurrence of multiple primary tumours in 7/10 homozygotes indicate a high cancer risk in homozygous women from non-BRCA1/2 families. CONCLUSIONS: Intensive breast surveillance is therefore justified in these homozygous women. It is concluded that diagnostic testing for biallelic mutations in CHEK2 is indicated in non BRCA1/2 breast cancer families, especially in populations with a relatively high prevalence of deleterious mutations in CHEK2. PMID- 22058429 TI - Linkage and association analyses of glaucoma related traits in a large pedigree from a Dutch genetically isolated population. AB - BACKGROUND: Despite extensive research on the genetic determinants of glaucoma, the genes identified to date explain only a small proportion of cases in the general population. METHODS: Genome-wide linkage and association analyses of quantitative traits related to glaucoma were performed: intraocular pressure, size and morphology of the optic disc (individual and combined by method of principal components) and thickness of the retinal nerve fibre layer (RNFL), in a large pedigree from a genetically isolated Dutch population. RESULTS: For the size of the optic disc, the study demonstrated a significant linkage signal (logarithm of odds (LOD)=3.6) at the LRP1B region on chromosome 2q21.2-q22.2 and significant association (p=8.95*10(-12)) with the previously reported CDC7/TGFBR3 locus at 1p22. For parameters describing morphology of the optic disc, the study obtained significant linkage signal (LOD=4.6) at regions SIRPA and RNF24/PANK2 at 20p13 (false discovery rate (FDR) based q value <0.05) and genome-wide significant association (p=2.38*10(-9)) with a common variant in the RERE gene at 1p36. Suggestive linkage and association signals indicated loci for morphology of the optic disc at 2q31-q33 (IGFBP2 locus) and for RNFL thickness at 3p22.2 (DCLK3 locus) and 14q22-q23 (SIX1 locus). CONCLUSION: This study identified new linkage regions at 20p13 (SIRPA and RNF24/PANK2 loci) and 2q33-q34 (IGFBP2 locus) for parameters describing morphology of the optic disc. The results of the study also suggested common genetic control of these parameters and RNFL thickness by SIX1 and doublecotin family genes. Finally, association signals for the recently reported RERE and LRP1B loci and the well known CDC7, TGFBR3, and ATOH7 loci were replicated. PMID- 22058431 TI - IDENTIFICATION OF READING PROBLEMS IN FIRST GRADE WITHIN A RESPONSE-TO INTERVENTION FRAMEWORK. AB - Models of Response to Intervention (RTI) include parameters of assessment and instruction. This study focuses on assessment with the purpose of developing a screening battery that validly and efficiently identifies first-grade children at risk for reading problems. In an RTI model, these children would be candidates for early intervention. We examined accuracy, fluency, growth, and teacher rating measures as predictors of child status (at risk, not at risk) at the end of the school year based on an unselected sample of 243 children. The prediction model that best fit our selection criteria included 2-word fluency measures and a teacher rating of reading problems. Word-fluency growth was an equally plausible choice statistically, but, because the measure would require an additional data point, it was not the most efficient choice. The receiver-operator characteristic curve analysis yielded an area-under-the-curve index of .96, which indicates the selected 3-variable model is highly accurate. PMID- 22058430 TI - Genetic basis of pain variability: recent advances. AB - An estimated 15-50% of the population experiences pain at any given time, at great personal and societal cost. Pain is the most common reason patients seek medical attention, and there is a high degree of individual variability in reporting the incidence and severity of symptoms. Research suggests that pain sensitivity and risk for chronic pain are complex heritable traits of polygenic origin. Animal studies and candidate gene testing in humans have provided some progress in understanding the heritability of pain, but the application of the genome-wide association methodology offers a new tool for further elucidating the genetic contributions to normal pain responding and pain in clinical populations. Although the determination of the genetics of pain is still in its infancy, it is clear that a number of genes play a critical role in determining pain sensitivity or susceptibility to chronic pain. This review presents an update of the most recent findings that associate genetic variation with variability in pain and an overview of the candidate genes with the highest translational potential. PMID- 22058432 TI - High-Speed Nonlinear Interferometric Vibrational Imaging of Biological Tissue With Comparison to Raman Microscopy. AB - Vibrational contrast imaging of the distribution of complex biological molecules requires the use of techniques that provide broadband spectra with sufficient resolution. Coherent anti-Stokes Raman scattering (CARS) microscopy is currently limited in meeting these requirements due to the presence of a nonresonant background and its inability to target multiple resonances simultaneously. We present nonlinear interferometric vibrational imaging (NIVI), a technique based on CARS that uses femtosecond pump and Stokes pulses to retrieve broadband vibrational spectra over 200 cm(-1) (full-width at half maximum). By chirping the pump and performing spectral interferometric detection, the anti-Stokes pulses are resolved in time. This phase-sensitive detection allows suppression of not only the nonresonant background, but also of the real part of the nonlinear susceptibility chi((3)), improving the spectral resolution and features to make them comparable to those acquired with spontaneous Raman microscopy, as shown for a material sample and mammary tissue. PMID- 22058433 TI - Research in India. PMID- 22058434 TI - The concept of bisexuality and psychiatry. PMID- 22058435 TI - Gita and mental sciences. PMID- 22058436 TI - The problems of Indian psychiatrists in an alien culture. PMID- 22058437 TI - A family and genetic study of primary affective disorders. PMID- 22058438 TI - Description and quantification of multiple family group interaction. AB - Multiple Family Group Interaction as a method of Family Therapy is reported with reference to its development, technique and procedure. A rating system for the categorization and quantification of the therapeutic processes is discussed. The main findings of analysis of 85 sessions are presented. PMID- 22058439 TI - Life events in depression. PMID- 22058440 TI - Neuroticism profile in coronary heart disease. AB - Thirty seven cases of coronary heart disease and 30 normal healthy controls were administered Hindi version of MHQ. The coronary heart disease patients scored significantly higher on total neuroticism, free-floating anxiety and somatic anxiety subscales of MHQ. PMID- 22058441 TI - A clinical study of 276 patients diagnosed as suffering from hysteria. AB - A clinical study of 276 patients diagnosed as Hysteria in the Department of Psychiatry, Unit-2, Christian Medical College, Vellore, during the period of 1970 1974 is described.This group of 276 patients formed 10.81% of the total new consultations during this period. 61.2% of these were females. The peak age of onset was 10-20 years. The majority were married. 75% of them had conversion symptoms, 20.3% had dissociative states, and 4.7% had both features. 52.5% showed possible precipitating factors. 66.0% h i d features of extraversion in their personality make up. 14.1% showed evidence of parental deprivation. There was over-representation of the early born. Somatic symptoms (aches and pains) was the most common mode of presentation. The other common clinical manifestations were fainting attacks, "fits", vomiting, involuntary movements and paralysis of limbs. The immediate follow up showed that 11 patients recovered, 120 improved, 3 were unchanged and 1 patient became worse. Only 93 patients could be contacted for the final follow up. Among these, 28 recovered completely; 50 were improved; 2 became worse and 2 died.It is emphasized that Hysteria continues to remain a clinical entity. PMID- 22058442 TI - Depressive disorders and family constellation. PMID- 22058443 TI - Morbid grief-its clinical manifestation and proposed classification. PMID- 22058444 TI - Study of suicidal risk factors in depressive illness. AB - A statistical analysis was done to study the association of some environmental factors with Depressive illness, and suicidal tendency. All the factors studies were statistically significant. PMID- 22058445 TI - Junenile delinquency in girls ii. The application of the jesness inventory. AB - The use of the Inventory with 3 groups of girls is described-75 normal girls studying in 10(th) standard, 75 girls in an approved school with criminal record and 75 girls in the approved school requiring 'care and protection'. The results indicate that most of the sub-tests of the Inventory discriminate the delinquents from the normals. The results are compared with American and British studies. The usefulness of the Inventory in an Indian Setting indicated and future research trends are identified. PMID- 22058446 TI - Mental morbidity among graduate and research students : an epidemiological study. AB - A cross sectional epidemiological study of mental morbidity among 1160 postgraduate and research students was done by census method. Goldberg's 60 item GHQ was used as screening tool and a person scoring 12 and above was taken as a case. The response rate was 92.5%. A prevalence rate of 16.63 was found. The relationship between mental morbidity and selected socio-demographic, motivational psychological variables; certain life experiences in the campus was studied. The results are discussed. This study is first of its kind in our country. PMID- 22058447 TI - Changing psychiatric manifestations of neurosyphilis over a period of 23 years. AB - Cases diagnosed as general paralysis of insane at the psychiatric services of NIMHANS for 23 years from 1955 to 1977 were studied to analyse the trends of age distribution, sex proportion, annual admission rate and clinical categories. It was found that the mean age and the proportion of females did not show any impressive change during these years.Among the clinical categories the simple dementia type showed a considerable rise over the years.The acute confusional type showed a definite decrease during this period. A less impressive but definite decrease was found in the expansive type. Depressive form of GPI found in a considerable proportion of cases earlier has rarely been seen over the last one decade.The schizophrenic type has not shown any significant change.These findings are discussed in comparison with the earlier studies both in India and abroad. The possible causes of these trends are outlined. PMID- 22058448 TI - Helping the chronic schizophrenic and their families in the community-intial observations. AB - There is a growing interest in the problems of mentally ill persons in the community in order to understand and organize services for them. Schizophrenia continues to form the most important problems in the community. The present prospective study involved thirty patients with chronic schizophrenia and their families. The study involved the intensive understanding of the social problems of the patients and families as well as the interventions to manage the problems isolated.THE STUDY REVEALED THE FOLLOWING AREAS TO THE SOURCE OF PROBLEMS OF ADJUSTMENT: (i) High expectations of the family, (ii) Excessive emotional involvement, (iii) Marital disturbances, (iv) Problems of employment and (v) Problems relating to long term treatment.The techniques employed in the management were, in addition to long-acting phenothiazines were: (i) periodic and regular home visits, (ii) family financial counselling, (iii) explanation about the illness to enhance treatment acceptance, and (iv) contact with social welfare agencies. The paper is largely descriptive and illustrations of cases are included to highlight the salient aspects of the experience. PMID- 22058449 TI - Inter-relationship between drug use, anomie, alienation and autthoritarianism amongst university students. AB - The degree of addictive substance usage score and three personality variables, namely, authoritarianism, alienation, and anomie were measured in 197 university students through a self-administered questionnaire. WHO's Youth Survey Questionnaire for drag use, Varma et al.'s scale of Authoritarianism, Srole's scale of Anomie, and Pearlin's scale of Alienation, were used. A study of the relationship between the co-variables was studied and is discussed. PMID- 22058450 TI - A study of psychiatric referrals in a general hospital. AB - In-patient as well as out-patient psychiatric referrals at Safdarjang Hospital, New Delhi were studied during a short period of 21/2 months. The data were analysed with respect to referral rate, sources of referral and psychiatric diagnosis as made by the referring unit, compared with the diagnosis arrived at the department of Psychiatry. The results have been discussed in the study. PMID- 22058451 TI - Healing practices in psychiatric patients. PMID- 22058452 TI - The problem-oriented approach in psychiatry. AB - The problem-oriented approach to record keeping developed by Lawrence Weed is having a significant impact on the practice of Psychiatry. In this system, the physician is required to identify list and number all the patient's psychiatric, social and physical problems. The problem list is kept at the front of the record, much like a table of contents. All subsequent data including the clinician's plans and progress notes arc cross-indexed to the numbered problems. A plan for approaching each problem is constructed with the help of the list of assets and resources which include patient's existing or potential characterological strengths, vocational skills and talents, as well as resources and supportive factors within the family and community. At regular intervals progress notes are made which may be classified as subjective, objective or related to the treatment plan.This system is aimed at effective patient-care because the information can be easily retrievable and thus can be thoroughly analysed, correlated and synthesized into an ongoing treatment plan. Some problems posed by the system are discussed and the author offers a simple practical mode of recording. PMID- 22058453 TI - A comparative evaluation of dothiepin (prothieden) and imipramine. PMID- 22058454 TI - 1981-year of the handicapped. PMID- 22058455 TI - Depressive illness in children-a review. PMID- 22058456 TI - Electrocardiographic changes during lithium treatment. PMID- 22058457 TI - Sex chromosome aberrations in schizophrenia. AB - Research on sex chromosome aberrations has made considerable progress. There are evidences that possession of an extra X chromosome may affect the mental health of an individual. All the male schizophrenia patients registered during the period of study, who were not under treatment, constituted the patient sample. They numbered two hundered eighty seven. A properly matched control sample of two hundred thirty three healthy persons was also examined. Nuclear sexing and Karyotype was done for (a) all the chromatin positive cases in patient as well as control sample (b) ten per cent cases of normal XY individual's of patient sample(28) and control sample (23) Photography was done for the positive slides. The patients who showed chromation positive XXY pattern were studied further clinically along with Rorschach test and Bhatia battery. The schizophrenics showed more prevalence of chromatin positive than the control sample. PMID- 22058458 TI - Habituation of alpha attenuation responeses in depressed patients and normal subjects. AB - Habituation of alpha attenuation responses (AAR) obtained from a group of 20 depressed patients was compared with a group of 20 matched normal controls. The slope of the AAR habituation curve over trial showed that the normals habituated much quickly than those of patients. The findings were interpreted in terms of the level of arousal of the patients/subjects tested. PMID- 22058459 TI - Guilt and hostility in depression. PMID- 22058460 TI - d-AMPHETAMINE AS A PREDICTOR FOR RESPONSE TO IMIPRAMINE AND AMITRIPTYLINE. AB - Patients with endogenous depression fulfilling Feighner's criteria were included in the trial. All had pretrial scores above 20 on Hamilton's depression rating scale.Drugs were divided into groups A and B. Group A comprised of placebo and d amphetamine. It was found that all patients who improved with d-amphetamine also improved with tricyclics. Two who did not improve with d-amphetamine did not improve with tricyclics. PMID- 22058461 TI - EVALUTION OF UNILATERAL ELECTRO-CONVULSIVE THERAPY (A double blind study). AB - A double blind study of one hundred twenty patients ( ninety schizophrenics and thirty depressives )-who were divided equally into three groups, who received either (a) bilateral ECT or (b) unilateral application of electrodes on non dominant hemisphere or (c) unilateral on dominant hemisphere was conducted. The three groups were compared regarding efficacy of the therapy, effects on memory, speed of recovery from each shock session and lastly changes in the electro encephalogram.It was found that all the three techniques were more or less equal in therapeutic efficacy. There was no significant difference between them in the speed of recovery, nor in the EEG changes. Only difference was that in the field of memory, unilateral non-dominant group showed significant improvement in the 'immediate verbal recall' component of memory in particular. Results have been discussed in view of the current literature on the subject. PMID- 22058462 TI - Sintamil in the treatment of depression : a comparison of single vs. Divided dose administration. PMID- 22058463 TI - Thyroid function in different psychiatric disorders. AB - Thyroid function viz. estimation of T(3), T(4) & TSH (Thyroid Stimulating Hormone) were studied in cases of depression, mania and schizophrenia, each category numbering thirty one. These values were compared with corresponding values estimated in norm.al control group of individuals of identical age, sex and socio economic status. The depressives and schizophrenics showed subclinical or chemical hypothyroidism while the manic showed slightly higher values for T(3), and T(4), when compared to normal control subjects. PMID- 22058464 TI - Suicide in madras. AB - Eighty seven cases of suicides were investigated in the present study. Of the 87 cases 44.% were males and 56.2% were females. 7%of the females were below 30 years and most of them were married. The chosen choice for the fatal self destruction in both sexes was hanging and the selected fateful hour in a considerable proportion of cases was between 6.00 P.M. and 12.00 midnight Some of the notable causes are discussed. PMID- 22058465 TI - The scientific investigation of rebirth cases problems of field work and in the analysis of data. PMID- 22058466 TI - HYSTERIA OR HYPOGLYCAEMIA (A case Report of Insulinoma). AB - A case of Insulinoma is presented here because of the uncommon and peculiar clinical manifestation in the form of fits of unconsciousness with bizzare movements of limbs, which were considered to be due to Conversion Reaction and treated as such for a period of two years without any success. She recovered and was relieved of symptoms after surgery. PMID- 22058467 TI - Trichobezoar and mental retardation. PMID- 22058468 TI - A plea for national institute of psychiatry. PMID- 22058469 TI - Psychiatric morbidity among parents of schizophrenic patients. PMID- 22058470 TI - A psychoticism scale in hindi : I. Construction and initial tryouts. AB - A psychoticism questionnaire was designed constituting 110 questions framed on the basis of the following constructs: desocialization, paranoia, thought disorder, depression, perceptual disturbance, superstitions and mania. In the initial tryout, it was administered to 40 psychotics, 40 neurotics and 40 normals and 40 items inadequately discriminating between psychotics and normals/neurotics were deleted. The revised questionnaire was administered, in second tryout, to 50 psychotics, 50 neurotics and 50 normals. The results were again subjected to item analysis and 10 more items were deleted as they could not discriminate significantly between neurotics and psychotics or where they discriminated between normals and neurotics. Kuder-Richardson formula 20 was used for reliability and criterion validity was assessed by comparing the three diagnositic groups with one another. Both these were satisfactory. Thus a psychoticism questionnaire of 60 items was constructed. PMID- 22058471 TI - A psychoticism scale in hindi : ii. Standardization. AB - A psychoticism questionnaire in Hindi consisting of 60 items was standardised by administering it to 100 psychotics (schizophrenics and manic-depressives), 100 neurotics, 100 psychiatrically normal relatives of psychotics and 100 normals. The mean psychoticism score (P-score) of psychotics, neurotics, relatives and normals were 30.69, 13.63, 13.85 and 8.83 respectively, were significantly different from one another except for the difference between neurotics and relatives. The scores in each diagnostic group were normally distributed. Reliability as measured by Kuder-Richardson formula, split half, and test-retest methods gave coefficients between .62 and .88. Criterion validity as measured by comparing the diagnostic groups according to proportion of subjects in top, middle and bottom thirds; concurrent validity as assessed by correlating the P score with scores obtained on PEN scale and on Paranoid and Depression sub-scales of Personality Traits Inventory nad cross-validity studied by comparing our scores on psychotics with those obtained at three other centres in India were satisfactory. The questionnaire could well discriminate between psychotics and non-psychotics, and a satisfactory cut-off point has been suggested for this.On the basis of above findings we can conclude that the questionnaire constructed is a valid measure of psychoticism.Since a personality trait is presumed to have a normal distribution in the population, and we have obtained normal distribution on psychoticism score for each of the groups separately, psychoticism score studied here may refleet a personality trait. PMID- 22058472 TI - An opinion survey about the causes and treatment of mental illness and the social acceptance of the mentally ill patients. AB - In the present study assessment of Public Opinion of two groups, relatives and non-relatives attending the out patient department with the patients, were done. Analysis of the data revealed that both groups held heredity as the cause of mental illness and both groups preferred, significantly the efficacy of Psychiatric treatment like E.C.T. and drugs to that of Homoeopathic and Ayurvedic treatment, Magic and faith healing procedure, not preferred to any significant extent. Regarding efficacy of treatment of the mentally ill we find that significantly more number of relatives did favour E.C.T. and drugs. Psychotherapy has yet to make a mark. PMID- 22058473 TI - Clinical aspects of dyskinesia. PMID- 22058474 TI - Phenomenology of 'escape' from a mental hospital in India. AB - Escape phenomenon is studied in a mental hospital in a retrospective design. From among the 3892 admissions of 1977, 128 case files of patients who were escapees according to the definition used, were picked up. The incidence of escape for the year 1977 was 3.3%. Results on different variables were compared with hospital admission statistics for the year 1977 to draw inferences. Using a Chi-aquare test it was found that escape incidence was significantly high in the below 30yr. age group, males, free voluntary boarders, manics and schizophrenics. The type of ward from where escape was made, the duration of their stay in the hospital before escape, and the clinical status at the time of escape were also examined. The implications of the results are discussed. PMID- 22058475 TI - Psycho-social problems of long stay mental patients. AB - One hundred and ten inpatients (80 males and 30 females) of Agra Mental Hospital with continuous stay of more than two years formed the study population. Majority of them were schizophrenics. Demographic data of these patients, their current social contacts inside and outside hospital, attitude of hospital staff and family members toward them, self care, sexual problems, future plans, social acceptability and their employability have been reported. PMID- 22058476 TI - Non-intellectual factors in learning disability. AB - 100 cases of learning disability are investigated to study non-intellectual factors associated with it. The study reveals that urban area, middle class, unitary and small family show high incidence. Impaired relationship with the parents is the most significant factor, followed by adverse influences in school. The findings are discussed. PMID- 22058477 TI - Functional neurosurgery in psychiatric illnesses. PMID- 22058478 TI - Psychiatric morbidity in a children's home. AB - Sixty-two inmates of a children's home were examined by using a symptom check list and Hindi adaptation of Stanford Binet Intelligence Scale-Form LM (1960). A high proportion (69.4%) of the inmates had one or other psychiatric problem. Mild mental retardation (I. Q. 50-70) was most common (40.3%), 11.3% were diagnosed as having unsocialized disturbance of conduct. Four most common psychiatric symptoms were stealing, quarrelsome behaviour, destructive behaviour and bed wetting. No significant correlation was found between psychiatric illnesses and present age, duration of stay and age at entry into the home. PMID- 22058479 TI - Social adjustment of 116 adult epileptics. AB - Social adjustment of 116 adult epileptics who had attended the out patient department of Agra Mental Hospital during a period of 3 years was studied through a follow-up investigation. Adjustment was recorded 'good' in 34.5%, fair in 19.8%, poor in 22.4% and very poor in remaining 23.3% cases. PMID- 22058480 TI - Intraocular pressure changes following modified e.C.T. AB - Intraocular pressure changes following modified ECT with and without succinylcholine were studied in Sixty cases. The pressure rose in both the conditions though the rise was more marked and longer lasting when succinylcholine was used. PMID- 22058481 TI - Post-psychotic depression in schizophrenics: (a prospective study). AB - The study consists of 44 Schizophrenic patients. All the patients were the first admission cases and treated for the first time within 6 months of their illness. The subtype Schizo affective schizophrenia was not included. Cases were studied and treated initially in the hospital. After recovery from the psychotic episode, they were followed up in the community for a minimum period of one year, during which 4 cases went into an unequivocal, depression. Pheaomenological aspects of the depression and a prediction of variables in terms of socio-demographicand the clinical state of cohort has been attempted. PMID- 22058482 TI - Therapeutic efficacy of doxepin in divided and single dose regime. PMID- 22058483 TI - MURDER IN TAMIL NADU(A Study of Murder Trials of 1968). AB - The murder trials of 1968 in Tamil Nadu totalling 526 are studied and assessed on the pattern of the U. K. Home Office study. The results showed that there were six psychotic murderers, 16 murderers who attempted suicide, 483 'normal' male murderers, 20 female murderers and 6 youthful murderers. Age, sex, method of killing and motives of the murderers are discussed. The implications of the study with reference to the penal institutions and prevention of crime are dealt with. PMID- 22058484 TI - Psychiatric morbidity and referral in general practice-a survey of general practitioners in bangalore city. AB - 60 General practitioners having M.B., B.S. qualification from all age group practicing in Bangalore city's centrally located locality were personally visited and a specially designed proforma was administered to find out whether they come across Psychiatric patients in their general practice, if yes what percentage of their practice ? Whether they referred any cases for Psychiatric consultation, what factors determined their decision to refer a case to the psychiatrist.9% General practitioners reportedly were seeing Psychiatric cases, on an average 10% of total patients seen by GP's were suffering from Psychiatric illness. 85% GP's had referred cases for Psychiatric consultation and factors which determined GP's decision to refer a case were : Request from patient to see a Specialist, patient was excited and unmanageable, pressure from relatives of patients serious impirsonment of patients' working capacity, patient finds it more acceptable to be told by a Specialist that he has nervous trouble, lack of emotional support from family of patient. Less commonly given reasons inlcuded inability to diagnose a case, for confirmation of diagnosis and treatment, for detailed examination and investigation, for better managment, resistant casses and lack of time to deal with Psychiatric problems. These findings have been discussed and their implications in planning further services have been highlighted. PMID- 22058485 TI - A COMPARATIVE STUDY OF MMPI PROFILES OF PSYCHIATRIC PG's v/s MEDICAL PG's. AB - MMPI profiles of 10 psychiatric PG's have been compared with 10 medical PG's. The findings are discussed statistically and otherwise. Both the groups fall within the range of normal. Some interesting findings are not unexpected, if a larger section of population could be studied preferably over a span of few years. PMID- 22058486 TI - Non-medical drug use among interns and house-officers. AB - Self-administered questionnaire was given to a sample of 105 interns and house officers working in Govt. Medical College, Jammu. Questionnaire was designed to obtain information about socio-demographic characteristics, the frequency of non medical drug use during the last one year and to enquire about "reasons" for drug intake. It was found that drugs commonly used were alcohol, tobacco, tranquillizers, amphetamines, cannabis. Most of the subjects used the same for 'company', festivity or curiosity. PMID- 22058488 TI - Psychic seizures-a case report. PMID- 22058487 TI - Lithium neurotoxicity at 'therapeutic' levels a case report. AB - A case of a young manic patient who developed severe neurotoxicity when on lithium alone has been presented. Investigations did not reveal presence of any infection, electrolyte imbalance or rise in lithium level.The possibility of lithium producing neurotoxicity at therapeutic levels for as yet unknown reasons is pointed out. It is suggested that this element of risk be considered when starting lithium for therapy or prophylaxis of affective disorders. PMID- 22058489 TI - Training for mental health team. PMID- 22058490 TI - Psychiatric services through peripheral health centres. PMID- 22058491 TI - The study of efficacy of family ward treatment in hysteria in comparison with the open ward and the outpatient treatment. AB - A comparative study of the efficacy of treatment of hysterical patients is made among three group of patients-patients treated in family wards, open wards and out-patients. The number of patients is fifteen in each group and they are matched for age, sex, per capita income, duration of illness and type of illness. Significant differences among three groups on certain parameters like personality have been eliminated. The results are discussed. PMID- 22058492 TI - Mental morbidity and urban life-an epidemiological study. AB - A survey of the mental morbidity of an urban group and two rural groups was made with the same method, same operational definition of a case and by the same team. The aim was to find out the nature and extent of the difference in their rates of morbidity and to identify the psychosocial variables associated with this difference. It was found that the rate of total morbidity was significantly higher in the urban group than in the rural groups. Psychosis was, however, commoner among the Brahmins, a rural group. The wide difference in the rates of mental morbidity between the urban and rural groups was mainly due to the difference in the rate of neurosis (165.3/1000, 51.6/1000 and 1.5/1000 respectively). The rate of neurosis in its turn was considered to be positively correlated with certain psychosocial characteristics irrespective of urban or rural residence of the group concerned. PMID- 22058493 TI - Extent and pattern of alcohol use and alcohol-related problems in north India. AB - A structured questionnaire was verbally administered individually to a random sample of the general population, 18 years of age and older, of rural and urban Chandigarh and of two villages in Jullundur district, Punjab. Out of a total of 1031 respondents, 23.7 percent were current users, 16.0 percent admitted of alcohol use in the past but were not current users, and 60.3 percent had never had alcoholic beverages. 19.0 percent of Chandigarh urban sample, 31.4 percent of Chandigarh rural sample and 45.9 percent of Jullundur rucal sample were current users. These findings have been discussed in terms of various socio-demographic variables. PMID- 22058494 TI - Alcoholic hallucinosis and paranoid schizophrenia-a comparative (clinical and follow up) study. AB - In a Study Of 90 patients of Alcoholic Hallucinosis and 30 patients of Paranoid Schizophrenia, it was found that delusions, delusions of infidelity, third person and running commentary auditory hallucinations and insight were not different in the two groups.Delusions of grandeur, passivity, thought echo and thought broadcast were significantly more frequent in paranoid schizophrenic patients. Anxiety, visual iiafracinatians and hallucinations in more than one modality at the same time were commoner in alcoholic hallucionsis. Recovery from acute symptoms was much earlier in alcoholic hallucinosis.Number of first degree relatives with schizophrenia was much higher in the paranoid schizophrenic group.In a mean follow up period of 18 months, it was found that patients with alcoholic hallucinosis did much better than patients with paranoid schizophrenia. PMID- 22058495 TI - ANDROGYNAE, 17 KETOSTEROID EXCRETION AND M-f PROFILE IN MENTAL ILLNESS. AB - For centuries it has been a common belief that any abnormality of physique is an accompaniment of mental illness. Recently interest has been focussed on the degree of masculinity or conversely feminity in the constitution. An index of this parameter called 'androgynae' can be derived from Taner's formula. Physique acts as a manifestation of the gene complex mediated possibly through endocrines and hence should reflect on the excretion pattern of 17 ketosteroids. Personality being a constitutional variation, it ought to be related to physique and in turn to the androgenic activities. M-f profile of the MMPI should locate such variation in that case. Present work was planned to find out implication of each of these parameters and to see if there is any correlation between them. It was seen that the psychiatric patients had low androgynae scores than the normals but the 17 ketosteroid excretion was higher. This was unexpected. M-f profile of the patients did not show any significant difference from the control. Results are discussed in the light of available literature. PMID- 22058496 TI - A study of delinquent boys using jesness inventory. AB - The Jesness Inventory was administered to two groups; one consisting of 100 institutionalised delinquents and the other of 100 students of the school leaving class in a local school. The results suggest that some of the sub-tests of the inventory significantly discriminate between the delinquent and the non delinquent normal boys.These results have been studied in the light of earlier data of British and American Workers. PMID- 22058497 TI - Thyroid function in depression. AB - Studies on thyroid functions were performed on patients suffering from depression and compared with normal control group. 31 different cases of depression were studied for their thyroid function andshowed a diminished level of T(3) and T(4) with a concomitant rise in TSH level. When the female population of these 31 cases was compared with their male counterparts the females showed a significantly lower thyroidal functional status than the males. PMID- 22058498 TI - Socio-demographic factors of depressive disorders in India: a comparative appraisal. AB - Socio-demographic study of 173 cases of depression was carried out prospectively over one year's period from January 1977 to December 1977, at the psychiatric out patient department of Kasturba Medical College Hospital, Manipal, Karnataka. The findings are compared with the data reported from other centres in India and the results are discussed. PMID- 22058500 TI - A comparative study to evaluate the efficacy of spaced v/s daily electroconvulsive therapy in schizophrenia. PMID- 22058499 TI - Neurotic disorders in children: a psycho-social study. AB - Thirty neurotic children and their parents seen consecutively at the C.G.C., Institute of Medical Sciences, Varanasi, were studied with the help of a structured interview schedule and were subjected to detailed psychiatric assessment. The results were compared with that of thirty normal children and their parents who were studied in a like manner. Hysteria was found to be the commonest type of neurosis seen in C.G.C. population, followed by anxiety neurosis. In a number of cases there was a close similarity between symptoms presented by the children and the symptoms of parents who were suffering from neurotic or physical illness at the same time. The relevance of these findings are discussed. PMID- 22058501 TI - Suicide in rural community. AB - 51 suicides in a rural community of Northern Karnataka were studied for incidence, age and sex distribution, methods adopted for suicides, and causes of suicides. Suicides in rural area did not show any difference from urban suicide pattern. PMID- 22058502 TI - Value of propanidid in electro convulsive therapy (comparison with thiopentone). AB - Propanidid due to its fast induction, early recovery and absence of cumulative action avoiding post recovery hangover is a useful agent and a better substitute for the established inducing agent, thiopentone It has all the advantages of thiopentone but lacks tbe disadvantages of the same. Its extremely short duration of action suits the short procedure of electroconvulsive therapy which gets over within one or two minutes. Use of propanidid will allow more number of E. C. Ts to be given in out patient department and will help in reducing the load on the hospital staff without compromising the safety of the patients. PMID- 22058503 TI - Response of pineal gland in clinical cases of psychological stress. AB - The present study includes 50 patients suffering from psychological stress disorders like thyrotoxicosis and anxiety neurosis. Biochemical estimation of melatonin was done in all these cases prior to treatment and 3 months after appropriate treatment. A significant increase in the level of melatonin was observed in thyrotoxic and anxiety neurotic cases. In all these cases, after therapy the level of melatonin was found to be within the normal limits. These observations confirm the finding that there is a pineal response to psychic stress. PMID- 22058504 TI - Tricyclic anti-depressant induced mania. AB - The authors report four cases of Monopolar Depressed patients who developed manic features for the first time while on tricyclic antidepressant therapy. The phenomenon is viewed as tricyclic antidepressant induced mania. The manic symptoms occurred late in therapy, with moderate doses of tricyclic antidepressants (125-150 mg per day) and were easily controlled with antipsychotic medication. Factors relating to age of patients, metabolic products of tricyclic antidepressants and central nor-adrenergic and dopaminergic systems are considered important and their role has been discussed. PMID- 22058505 TI - Prevalence of psychiatric disorders in ahmedabad (an epidemiological study). AB - A psychiatric survey was carried out in an urban area of Ahmedabad which consisted mainly of middle class population. 461 families were surveyed which consisted of a total number of 2712 persons.The data was collected in a predetermined form. The index cases were individually evaluated in detail with the help of a structured Psychiatric proforma, case work and psychiatric examination by a consultant for psychiatric diagnosis. Out of the total of 2712 persons surveyed, 128 were found to be suffering from psychiatric disorders, the prevalance rate being 4.7% (47.2 per thousand). PMID- 22058506 TI - Behavioural and tetratogenic effects of solar eclipse. PMID- 22058507 TI - Teenage drinking-a plea for intervention. PMID- 22058508 TI - Body/Mind from dichotomy to double-bind. PMID- 22058509 TI - Mental health and ageing in India. PMID- 22058510 TI - Family structure and mental illness in old age. AB - A random sample of subjects aged over 60 in the community was studied. Out of 181 subjects studied 50 were found to suffer from functional disorders such as depression and anxiety, and 11 from organic brain syndrome. 120 are found psychiatrically normal. Over 50% of the elderly subjects studied were widowed and about 70% were unemployed and nearly 80% belonged to lower middle class and low socio-economic group.The families of the elderly subjects and their living condition were studied in detail. The family was divided into 'joint', 'nuclear' and loosely joint' on the basis of living arrangement financial support and other help they received. Functional disorder was found high in old age subjects living in nuclear family and living alone. 33 psychosocial variables affecting the health of the elderly subjects were studied and their correlation to psychiatric illness was determined, by computer. Further factorial analysis was carried out, and three factors were extracted. It was found that Factor II and Factor III were about family and living conditions. Hence it could be stated that the family and living conditions are significant factors affecting the mental health of the elderly subjects. PMID- 22058511 TI - Social dysfunctioning as a measure of severity of psychiatric illness. AB - A study was carried out to examine the validity of social dysfunctioning as a measure of severity of illness. Modified version of KAS, R2 inventory was used to measure social functioning. Since there can be no absolute measure of severity of psychiatric illness, the validity was tested through indirect means. It was decided that if the scores on social dysfunctioning were higher amongst the mentally ill compared to normals, higher in Psychotics compared to Neurotics and higher in those assessed by a relative as well as the Consultant Pyshciatrist to be more severely ill than those judged as less severely ill, the validity of social dysfunctioning as a measure of severity of Psychiatric illness would stand established. This was indeed found to be the case in the study which was carried out with 200 consecutive patients from a psychiatric out-patient department and their matched normal controls. PMID- 22058512 TI - Social interaction and neuroses (the family and the primary group): a pilot study. AB - The present work examines the social interaction with the primary group of 30 neurotic patients and 30 matched controls. A comparison of the degree of family jointness in the two groups was also done keeping in view the nature of Indian family system and to find out the association, if any, it bears to social interaction. Evaluation instruments were Social Interaction Schedule (Henderson et al., 1978) and Khatri's Scale to Measure Jointness of Families in India (1970). The findings indicate that neurotic patients do not have a deficient primary group, as far as the numerical size and the duration and type of interaction is concerned. However, the patients appear to be less active than controls in making contacts with members of their primary group outside their household. Further, our group of patients perceived their personal lives to be deficient in some respects. Patients and controls did not differ with regard to the degree of family jointness as measured on Khatri's Scale. PMID- 22058513 TI - Psychiatric morbidity in general practice-a preliminary report. AB - No study of psychiatric morbidity in general practices is reported in India. A three phase study of psychiatric morbidity in General practice is nearing completion in a group general practice in Bangalore. This preliminary report covering the available data from the first phase indicates a psychiatric morbidity of about 36% in general practice. PMID- 22058514 TI - Do the psychiatric patients reject themselves? AB - Five statements measuring social distance from and prejudice against the ex mentally ill were read to 137 psychiatric patients and relatives from urban background. Their agreement and disagreement with the five statements was analysed and compared with controls from an orthopaedic clinic.Maximum social distance was found on statements about establishing marital relationship with an ex-mental patient. The social distance was found less frequently in working in a mental hospital; sharing same house, falling in love and working with an ex mental patient respectively. The psychiatric patients and their relatives are more rejecting than the controls. PMID- 22058515 TI - Hysteria-a psychodemographic study. AB - The study refers to Sixty five cases, diagnosed as Hysteria in the course of one year in a general hospital clinic. High occurrence was seen in the age group of 16-20 years. Mean age was 19.1 years. Females formed the majority of the patients (63.1%). Occurrence was higher in unmarried males and females. Illness was more common in persons with lower education and socio-economic status. Nuclear families harboured greater number of the patients. Various psychogenic factors and the symptoms observed are discussed. During the follow up period, which was spread over a period of two years, it was observed that twenty two patients (33.8%) got rid of their symptoms altogether whereas fourteen of them (21.5%) had only partial relief. PMID- 22058516 TI - LITHIUM AND KIDNEY: (A study of renal biopsy in Lithium patients). AB - A study of renal biopsy in 13 lithium treated patients is reported. The light microscopic changes were non-specific and comprised glomerular hypercellularity; cloudy swelling of the tubular epithelium and interstitial fibrosis. Correlation between structural changes and functional alterations could not be established. The duration of therapy did not have any bearing on the intensity of the structural changes. No case of renal failure occurred in well controlled series as ours. PMID- 22058517 TI - Lithium treatment in affective disorders. AB - 50 manic patients of unipolar and bipolar affective illness were placed on oral lithium 600-1500 mg daily and serum levels in the range of 0.49-1.23 mEq/L. A better response in bipolar disorders than unipolar was observed. Besides, a much better response to lithium therapy is observed in patients with disease of longer duration and a positive history of affective illness in blood relations. Therapeutic effect had no relationship in terms of age or sex of the patients. PMID- 22058518 TI - Psychiatric disorders in children with temporal lobe epilepsy: a controlled investigation. AB - Twenty five children each with temporal lobe epilepsy and grand mal epilepsy, both diagnosed electroencephalographically were studied for psychiatric disorders. Temporal lobe epileptics had such disturbances much more oftener. The commonest diagnostic label in both the groups was behaviour disorder, followed by neuroses. Schizophrenia was seen only in temporal lobe epileptics. PMID- 22058519 TI - Psychiatric morbidity in pulmonary tuberculosis-a clinical study. AB - The prevalence of psychiatric morbidity in patients with pulmonary tuberculosis is significantly high. Depressive Neurosis is the commonest among them. The psychiatric morbidity is related to the duration of illness, the degree of incapacitation and the knowledge of sputum AFB positive status. More attention has to be paid to the psychiatric manifestations in chronic illnesses like tuberculosis in order to alleviate the mental sufferings of these patients. PMID- 22058520 TI - Psychiatric illness in suicide attempters. AB - Sample consisted of a series of 100 cases of attempted suicide who were hospitalized in medical or psychiatric wards of the two hospitals of Lucknow city during a period of two years. The study revealed about 80% subjects were in the age range of 15-34 years. Psychiatric disorders were observed in 62% of these subjects. 58% subjects had shown clinical features of abnormal personalities, usually of schizoid, hysterical or passive-aggressive type. Socio-demographic variables associated with self-destructive impulse were investigated. The enquiry also incorporates certain clinical impressions about 61% subjects who were followed-up for a period of two years. Two of the attempters committed suicide during the follow-up. PMID- 22058521 TI - Habituation of skin conductance responses in patients with anxiety States. AB - Habituation of the GSR responses obtained from a group of 20 patients sufferings from anxiety states was compared with a group of 20 matched normals, selected for lack of anxiety. Habituation parameter did differentiate the two groups very distinctly, where very fast habituation WP.S noted in the normals. Findings were interpreted in terms of the level of arousal of the patients/subjects tested. PMID- 22058522 TI - Nitrazepam in emotional disorders of childhood. AB - The therapeutic results obtained with Nitrazepam in 30 children with emotional disorders between 4 and 14 years of age are reported, 17 children with habit disorders, 6 with behaviour, 5 with personality and 2 with Neurosis. Employing a flexible dosage schedule, a dose of 1/4 tablet to 1 tablet of 5 mg. Nitrazepam once to thrice daily was effective and safe. 24 of the 30 children (80%) showed recovery or marked improvement with over 50% fall in percentage reduction in total score based on assessing the target symptoms. PMID- 22058523 TI - Depression in wilson's disease. AB - This study comprise of 23 patients of Wilson's Disease, who were assessed individually by a psychiatrist and neurologist separately. Clinically discernable psychiatric symptoms were detected in 11 patients. Depressed affect was the commonest finding in the series. While four out of five young patients showed depressive symptomatology, none of the six patients showed any depression. All four patients who had severely depressed affect were also patients who had most severe extrapyramidal features. PMID- 22058524 TI - Koro-like syndrome: a case report. PMID- 22058525 TI - Rabbit syndrome: patchy disapperance in stage 1 nrem sleep. AB - A case which fulfilled the clinical description of Rabbit Syndrome investigated with sleep E.E.G is presented. Unlike the earlier reports, a patchy disappearance of the movement disorder during Stage 1 NREM sleep was noticed. The clinical differentiating features from tardive dyskinesia are discussed. PMID- 22058526 TI - Family planning and mental health. PMID- 22058527 TI - Emotional factors in bronchial asthma. AB - Controlled study on 30 patients of bronchial asthma was conducted at General Medicine Dept. of Civil Hospital, Ahmedabad. It has been observed that parental loss or deprivation in childhood per se is a significantly important factor in asthmatics. Asthmatics are found to be reserved, detached, affected by feelings, emotionally less stable, mild, accommodating, shy, timid, tender-minded, dependent, tense and frustrated in comparison to the control cases. PMID- 22058528 TI - A comparative study of relative effectiveness of biofeedback and shavasana (yoga) in tension headache. PMID- 22058529 TI - Reliability of saliva lithium level-a prospective study. AB - 140 synchronous samples of serum and saliva, collected from 28 patients undergoing lithium therapy, were studied. The mean saliva/serum lithium ratio calculated for the first 120 synchronous samples from 24 patients was found to be 2.68 (population mean ratio). Regression line equation calculated for the same population came out to be Y=0.325 + 0.22X. Predictive value of saliva lithium level was tested by applying this regression equation and the population mean ratio on 20 samples from the next 4 patients. Prediction was also tried in the 24 patients who had given more than 3 synchronous samples by using the individual mean saliva/serum lithium ratio. An individual's mean ratio was calculated from the initial 3 synchronous samples and the predictive value of saliva was tested on subsequent samples in the same patient by using his mean ratio. This method of prediction was found to be better than predicting on the basis of population figures. But no method was found to be consistently reliable and therefore saliva lithium level is not a reliable indicator of serum lithium concentration. PMID- 22058530 TI - Is Western training relevant to Indian psychiatry? PMID- 22058531 TI - Prediction of response to tricyclic antidepressants with a single injection of methyleamphetamine. AB - Twenty five patients of endogenous depression fulfilling Feighner's criteria were selected for this study. It was found that the patients who improved with methylamphetamine responded to imipramine and those who did not improve with methylamphetamine improved with amitriptyline. PMID- 22058532 TI - Psychiatric evaluation of the spouses of female neurotics. AB - Fifty married female neurotics from outpatient clinic of G. M. & Associated Hospitals, Lucknow and their husbands were evaluated to investigate psychological disturbances in these husbands and to find out its relationship with the nature, severity and duration, of psychiatric illness in the wives. Personality characteristics and neurotic symptoms of the spouses were assessed on Eysenck Personality Inventory and Middlesex Hospital Questionnaire. 30 husbands were found to be sick but their illness does not seem to be related with the duration of marriage, severity and nature of wives' illness. Higher interspouse correlation on N-Scale of EPI was observed with increasing duration of illness in wives. PMID- 22058533 TI - A profile of the follow up of the rural mentally ill. AB - 108 Psychotic and 268 epileptic patients were followed up for 31/2 years as a part of an ongoing rural mental health care programme. Some of the observed situations, possible limitations and reasons for the evolved follow up pattern in this endeavour of non-institutional, family centred and community oriented treatment programme, are reported. The strategies to improve the follow up rate among the rural patients are discussed. PMID- 22058534 TI - Correlation between the adi self rating scale, the hamilton rating scale and clinical assessment of depression. PMID- 22058535 TI - Employability and work adjustment of epileptic patients. AB - Employability and work adjustment of all the 116 adult epileptics patients of Agra District who had attended the out-patient department of Agra Mental Hospital during a period of 3 years was studied through a follow-up investigation. 32.76% patients were found to be unemployed and among the gainfully employed patients and housewives 44.6% had satisfactory work adjustment, 32.4% had slight impairment, 28.6% moderate and 1.4% showed severe impairment and their occupational functioning. PMID- 22058536 TI - Mental health by the year 2000 a.d. PMID- 22058537 TI - Efficacy of lithium in schizophrenia. AB - 60 Schizophrenic patients were given LiCo(3)/Chlorpromazine for 4 weeks, in a double blind cross over study with two placebo crossovers of 1 week before and two weeks after active treatment. Several core schizophrenic features showed significant reduction in severity with lithium. However, CPZ treatment was superior in terms of improvement, as compared to the other group on MBPRS and CGIS. Target symptoms may be one situation, where lithium could be tried and these results are discussed. PMID- 22058538 TI - Acute schizophrenic episodes-are they schizophrenic? PMID- 22058539 TI - Attitude of parents towards their mentally retarded children. AB - Parents of 50 mentally retarded children were investigated for their attitudes towards their retarded children. Both the parents showed more negative attitudes toward their severely retarded child. In general mothers exhibited more negative attitude than the fathers. PMID- 22058540 TI - Role of walk-in-clinic in general hospital psychiatric units. PMID- 22058541 TI - Possession syndrome: an epidemiological study in west karnataka. AB - A house to house survey was conducted for a population of 1158 in west Karnataka to determine the prevalence of possession syndrome and to study people's attitude towards the same. One year period prevalence was found to be 3.7%. 90% of the respondents believed in possession. Women more than men shared this belief. Spirit possession was reported to be troublesome but God possession as helpful. Number of God possession cases exceeded tint of spirit possession. Female sex, young age, low education appeared to predispose an individual to get possessed in such atmosphere. PMID- 22058542 TI - Aspects of psychiatric morbidity in the out patient population of a general hospital in sri lanka. AB - A psychiatric morbidity study of a general hospital outpatient department population in Sri Lanka was done.A two stage sampling method was used. Questions which differentiated the psychiatrically morbid group were identified. The disease pattern was compared and contrasted with that presenting at psychiatric facilities in the area.Neurotic illness, the commonest being hypochondriasis was found to predominate in the general outpatient psychiatrically ill population in contrast to the population at in and out patient psychiatric facilities where schizophrenia was the major diagnostic category. PMID- 22058543 TI - Long term effects of cannabis. AB - 50 chronic cannabis users were studied for their physical, mental, cognitive and socio-economic aspects of health. They were given W.M.S., Bhatia Battery of intelligence and B.G.T. It was observed that only 12% provided clue for suspecting cognitive deficiency. No social breakdown phenomenon was observed in the sample. Also, no significant physical illness was detected in the subjects. PMID- 22058544 TI - Ect-chlorpromazine combination compared with chlorpromazine only in schizophrenia. AB - Forty-four hospitalized schizophrenic patients, 22 in each of two groups, were treated for a period of 6 weeks with either EGT-GPZ combination or CPZ alone. Ratings on RP scale (Rockland and Pollin, 1S65) showed that the KGT-receiving group was significantly better en several measure at second week and also had an earlier onset of beneficial response on "Affect and Mood." However, at the end of 6 weeks, these differences disappeared and on clinical Global Impression of Improvement the two groups did not differ significantly. The implications are discussed. PMID- 22058545 TI - Fluphenazine decanoate in chronic schizophrenia. PMID- 22058546 TI - Psychotic jealously: a phenomenological study. AB - Sociodemographic, clinical, marital and sexual characteristics of 50 consecutive patients having delusions of infidelity were studied. Females outnumbered males after excluding alcoholics. Most of the patients were older than 30 yrs. and the onset occured more than 20 yrs. after marriage in about half the patients. Male patients were more often eldest siblings as compared to females. About one third of the patients had a history of marital and sexual difficulties prior to onset. The "third person" involved in the delusion was often a family member, particularly in patients coming from joint families. Possible causes of tie-in between delusion of jealousy and social factors are discussed. PMID- 22058547 TI - Psychiatric morbidity and the menopause. AB - A sample consisting of Menopausal, pre menopausal and post menopausal women in the age range of 36 to 50 years was studied using a two stage screening procedure for identifying and assessing psychiatric morbidity. The screening device, General Health questionnaire (GHQ) identified 21 of the 105 women studied as 'possible cases'. On further interviews using standard psychiatric interview (SPI) a higher proportion of menopausal women were found to be psychiatrically ill. The predominant symptom in the Menopausal group was depression. Both menopausal women and women who had undergone hysterectomy (surgical menopause) received higher mean ratings on SPI. The inter-rater reliability of SPI was found to be high and was comparable to those reported by original authors. PMID- 22058548 TI - A psychiatric study of patients attending mehandipur balaji temple. AB - In the present study 100 cases, randomly selected were studied at famous shrine of Rajasthan, the Mehandipur Balaji. As regards the sociodemographic variables, patients were mainly between 15-39 years of age, 80% were educated, 82% had Urban domicile, 98% were Hindus and Females were 54%. Majority of the visitors being from Northern part of India. Failure of modern treatment and influence of family members and friends were the main motivating factors. Majority of patients were Neurotic (48%), followed by Psychotics (28%). Patients who developed trance (possession) were Neurotics. One quarter of the patients who were mainly psychoneurotics, showed improvement. PMID- 22058549 TI - Stability of serum lithium levels-usefulness and relevance in Indian conditions. AB - Two groups of patients on regular lithium therapy were studied to find out the stability in values of serum lithium over a period of time. Serum samples of one group was stored at -4 degrees C while that of other group at room temperature. These samples were subsequently analysed over a period of eight days and subjected to statistical analysis. It was seen that values on the first day did not differ significantly from values of subsequent days. Implications of this findings are discussed in Indian conditions as lithium estimation facilities are available only at a few centres. PMID- 22058550 TI - Pre-operative anxiety and its management in dentistry. PMID- 22058551 TI - Chronic mania following polioencephalomyelitis-a case report. AB - An interesting case of Chronic Mania following polioencephalomyelitis is presented. The case responded very well to conventional Lithium therapy. The case is reported because of its rarity. PMID- 22058552 TI - Treatment of encopresis with operant conditioning: a case report. PMID- 22058553 TI - Laurence-moon-biedl syndrome with schizophrenia (a case report). PMID- 22058554 TI - Dawn of precision in psychiatry. PMID- 22058555 TI - "Late paraphrenia" (a report from the geropsychiatric clinic, madurai, India). AB - A brief review of literature on Late Paraphrenia is offered. An analysis was made on 15 cases of late paraphrenia with reference to its frequency, sex distribution, hallucinations, delusions and sensory impairment. Late Paraphrenia formed 4% of all Geropsychiatry cases. All the cases had hallucinations (100%) while 14 had delusions (93%). An associated auditory and/or visual defect was noticed in 13 of the cases (87%).Follow up findings revealed a sustained remission for 4 to 5 years with drugs in 12 patients (75%) and one patient died from cerebral stroke. PMID- 22058556 TI - Evaluation of cognitive effects of ect (preliminary observations). AB - The aim of present double blind controlled study is to evaluate the effects of ECT in Schizophrenia and Depression. 20 depressed and 20 schizophrenic patients of either sex, in the age group 18 to 65 years fulfilling the inclusion and exclusion criteria were taken for study. The psychiatric evaluations were carried out before the treatment, and at the end of 3, 6, 8 and 10 treatments. Cognitive test battery was administered before the treatment and 48 hours after the last treatment. No Post ECT cognitive deficit was observed on the test battery though some patients did complain of forgetfulness subjectively. PMID- 22058557 TI - General hospital psychiatric clinic versus mental hospital setting: a study of socio-demographic variables in a novel experience. AB - A retrospective analysis of data showed that patients in general stayed for shorter duration in general hospital psychiatric clinic than in mental hospital. PMID- 22058558 TI - Life events and depression. AB - The life events occurring in a 6 month period preceding onset of illness in 50 OPD primary depressives were inquired into by a Life Events Inventory and compared with those in a corresponding time period of 50 matched controls. The relation between life events and the depth of depression at initial interview was also studied. The results are analysed and the probable pitfalls discussed. PMID- 22058559 TI - Life events, physical illness and psychiatric morbidity. AB - Sixty patients of pulmonary tuberculosis selected through a specified selection procedure from T. B. Hospital, Bikaner, were assessed by P. S. E. (Present State Examination). An open ended life event schedule was used to record the life events of past one year, which had some impact on the patient. Results indicate that the patients who had experienced life events had significantly more psychiatric symptom scores as compared to those who did not report a life event (p<.001). Further analysis showed that the significant difference were among the patients, who had more than one life events as compared to those who had no life event or only one life event (p<.01). Implications of the findings are discussed. PMID- 22058560 TI - Popular attitudes towards alcohol use and alcoholism. AB - In a study involving individual verbal administration of a structured questionnaire to 1031 respondents comprising a random sample of general population, 18 years of age and older, of urban and rural Chandigarh and two villages in Jullundur district, Punjab, 45.0 per cent felt that people could drink "none at all" without it having a bad effect on their health, and 26.2 per cent thought that they could have a few drinks once or twice a month. To another question, 32.1 and 34.1 per cent felt that it was "normal" to have one drink and two drinks respectively, on any one occasion, and only 16.9 percent responded that it was "normal" to drink "none at all". Alcoholics were identified by such behaviours as "being dead drunk", "drinking too much", having "arguments/fights" and being a "public nuisance".Current users gave the most permissive and non users the most restrictive responses as regards the norms of drinking. PMID- 22058561 TI - Plasma creatine phosphokinase in schizophrenia. AB - Plasma creatine phosphokinase (GPK) was estimated from unmedicated schizophrenics to evaluate its significance in the diagnosis. The mean value of CPK in schizophrenics is 78.41+/-5.78 IU/L (n=49) as against control value of 27.45+/ 2.27 IU/L (n = 36). The statistical analysis showed significance (p<0.05). The study finds its importance in view of the earlier reports suggesting the diagnostic value of C.P.K. PMID- 22058562 TI - Insight and lithium compliance. AB - In a study of lithium compliance in 35 patients with Manic Depressive Psychosis on prophylactic lithium it was found that insight into the nature of illness and drug compliance were unrelated. PMID- 22058563 TI - A comparison of a divided and a single dose regime of dothiepin and its therapeutic efficacy. AB - In a double-blind study the advantages of a once-a-day dosage of a tricyclic antidepressant as against a thrice daily dosage regimen was evaluated using dothiepin (Prothiaden) and matching placebo tablets. Twenty eight adult patients of both sexes participated in the study and were randomly allocated to drug treatment. Out of 28 patients who received dothiepin, 17 showed good improvement, in 6 improvement was fair and in 5 there was no improvement. These findings show that the response to dotheipin was satisfactory. Further, both treatments were equally effective in relieving symptoms of depression. PMID- 22058564 TI - Mental illness in 30 married couples. AB - Diagnostic characteristics, personality pattern and certain psychosocial variables of 30 married couples where both partners were mentally ill (group A) were compared with the findings with another group of 30 couples where only one partner was psychiatric patient (Group B). Results revealed that couples in the Group A had significantly longer duration of marriage as compared to Group B. Significantly higher number of pairs in the Group A were from the higher socio economic status. Nearly two third of the secondary partners (those developing illness later) in the Group A were wives. Primary partners of Group A (those developing illness earlier) had a significantly longer duration of illness than the sick spouses of Group B. PMID- 22058565 TI - Acute porphyria amongst psychiatric patients. AB - A total of 519 consecutive patients, admitted to psychiatric wards of two different hospitals, were screened for evidence of increased excretion of porphobilinogen in the urine by original Watson Schwartz test and modified Watson Schwartz test supported with quantitative estimation of porphobilinogen by Remington's method in search of cases of acute porphyria amongst psychiatric patients. An additional 273 normal healthy volunteers were also screened as controls. Two cases (0.38%) were found which could be unequivocally diagnosed to be suffering from acute intermittent porphyria amongst psychiatric patients. These cases belonged to the category of missed diagnosis being labelled as hysterical. Seven more cases were positive by modified Watson Schwartz test but the test was only transiently positive and the Ehrlichaldehyde reactor substance was unstable. In the absence of detailed enzymatic and family studies, these cases have been kept under the category of suspected prophyria. A significant number of psychiatric patients (12.9%) gave positive original Watson-Schwartz test but were negative for modified test. Similar reaction was seen in 2.6% of healthy controls. The significance of this finding needs to be evaluated. PMID- 22058566 TI - A victim of an epidemic of possession syndrome. AB - A case of young man who got possessed by a god and two spirits alternatively is reported. He was one of the four victims of an epidemic of possession by two spirits (Mohini). The epidemic occurred following the prediction that the two women who committed suicide, would become Mohinis and liaunt adult men. It appeared that the strong belief and expectation in the local culture made the index person who was otherwise well adjusted in life to get possessed. The implication of this finding is discussed. PMID- 22058567 TI - A case of de clerambault's syndrome with capgras phenomenon. PMID- 22058568 TI - Clonidine for opiate withdrawal. PMID- 22058569 TI - Psychosis in systemic lupus erythematosus-a brief review and case report. PMID- 22058570 TI - Kinetics of Neuraminidase Action on Glycoproteins by 1D and 2D NMR. AB - The surfaces of mammalian cells are coated with complex carbohydrates, many terminated with a negatively charged N-acetylneuraminic acid residue. This motif is specifically targeted by pathogens, including influenza viruses and many pathogenic bacteria, to gain entry into the cell. A necessary step in the influenza virus life cycle is the release of viral particles from the cell surface; this is achieved by cleaving N-acetylneuraminic acid from cell surface glycans with a virally-produced neuraminidase. Here we present a laboratory exercise to model this process using a glycoprotein as a glycan carrier and using real time nuclear magnetic resonance (NMR) spectroscopy to monitor N acetylneuraminic acid release as catalyzed by neuraminidase. A time-resolved two dimensional data processing technique, statistical total correlation spectroscopy (STOCSY), enhances the resolution of the complicated 1D glycoprotein spectrum and isolates characteristic peaks corresponding to substrates and products. This exercise is relatively straightforward and leads students through a wide range of biologically and chemically relevant procedures, including use of NMR spectroscopy, enzymology and data processing techniques. PMID- 22058571 TI - Parental Work Schedules and Children's Cognitive Trajectories. AB - Previous work has shown an association between mothers' nonstandard work schedules and children's well-being. We built on this research by examining the relationship between parental shift work and children's reading and math trajectories from age 5/6 to 13/14. Using data (N=7,105) from the National Longitudinal Survey of Youth and growth curve modeling, we found that children's math and reading trajectories were related to parents' type of nonstandard shifts (i.e., evening, night, or variable). We found that having a mother who worked more years at a night shift was associated with lower reading scores, having a mother work more years at evening or night shifts was associated with reduced math trajectories, and having a father work more years at an evening shift was associated with reduced math scores. Mediation tests suggest that eating meals together, parental knowledge about children's whereabouts, and certain after school activities might help explain these results. PMID- 22058572 TI - Unemployment in Families: The Case of Housework. AB - Unemployment has consequences for individuals, but its impacts also reverberate through families. This paper examines how families adapt to unemployment in one area of life-time in housework. Using 74,881 observations from 10,390 couples in the Panel Study of Income Dynamics, we estimate fixed effects models and find that individuals spend between 3 and 7 hours more per week in housework when unemployed than when employed, with corresponding decreases of 1 to 2 hours per week in the housework hours of unemployed individuals' spouses. We are the first to show that unemployment is associated both with a reallocation of housework to the unemployed spouse and an increase in the family's total household production time. The results also provide evidence for gender differences in adjustments to the division of labor during unemployment, with wives' unemployment associated with an increase in housework hours that is double the increase for unemployed husbands. PMID- 22058573 TI - Mobility of Nonsticky Nanoparticles in Polymer Liquids. AB - We use scaling theory to derive the time dependence of the mean-square displacement of a spherical probe particle of size d experiencing thermal motion in polymer solutions and melts. Particles with size smaller than solution correlation length xi undergo ordinary diffusion ( ~ t) with diffusion coefficient similar to that in pure solvent. The motion of particles of intermediate size (xi < d < a), where a is the tube diameter for entangled polymer liquids, is sub-diffusive ( ~ t1/2) at short time scales since their motion is affected by sub-sections of polymer chains. At long time scales the motion of these particles is diffusive and their diffusion coefficient is determined by the effective viscosity of a polymer liquid with chains of size comparable to the particle diameter d. The motion of particles larger than the tube diameter a at time scales shorter than the relaxation time tau e of an entanglement strand is similar to the motion of particles of intermediate size. At longer time scales (t > tau e ) large particles (d > a) are trapped by entanglement mesh and to move further they have to wait for the surrounding polymer chains to relax at the reptation time scale taurep. At longer times t > taurep, the motion of such large particles (d > a) is diffusive with diffusion coefficient determined by the bulk viscosity of the entangled polymer liquids. Our predictions are in agreement with the results of experiments and computer simulations. PMID- 22058574 TI - Tunable Encapsulation of Proteins within Charged Microgels. AB - The binding of cytochrome c to pH and thermoresponsive colloidal hydrogels was investigated using multiangle light scattering, measuring loading through changes in particle molar mass and root mean square radius. Loosely cross-linked microgels [composed of a random copolymer of N-isopropylacrylamide (NIPAm) and acrylic acid (AAc)] demonstrated a high loading capacity for protein. Encapsulation was dependent on both the charge characteristics of the network and the salinity of the medium. Under favorable binding conditions (neutral pH, low ionic strength), microgels containing the highest studied charge density (30 mol% AAc) were capable of encapsulating greater than 9.7 * 10(5) cytochrome c molecules per particle. Binding resulted in the formation of a polymer-protein complex and condensation of the polymer. Anionic microgels demonstrated a change in density ~20-fold in the presence of oppositely charged proteins. These studies of cytochrome c encapsulation represent a significant step towards direct measurement of encapsulation efficiency in complex media as we pursue responsive nanogels and microgels for the delivery of macromolecular therapeutic agents. PMID- 22058575 TI - Welfare Program Implementation and Parents' Depression. AB - This study examines how the frontline practices in welfare offices explain variation in program impacts on parents' depression. The study uses data from four large-scale experimental studies and conducts multilevel statistical modeling on 6,761 families in 22 local welfare offices. Analyses examine the ways that two program implementation practices (emphasis on quick job entry and personal client attention) are associated with program impacts on parents' depressive symptoms. Effects vary by the age composition of the parents' children, such that programmatic emphasis on quick job entry is associated with increases in depression among parents with preschool-age children but not among parents with school-age children. Findings have implications for research, policy, and practice. PMID- 22058576 TI - Aryliodine (III) Diacetates as Substrates for Pd-Ag Catalyzed Arylation of Alkenes. AB - An unprecedented application of aryliodine (III) diacetates as substrates in Pd Ag catalyzed arylation of alkenes is described. The mechanistic studies revealed that the binary Pd-Ag catalysis leads to the decomposition of aryliodine (III) diacetates to oxygen and aryl iodides followed by arylation of alkenes forming Heck-type products. Under optimized conditions both electron-rich and electron deficient alkenes undergo arylation in high yields. Advantageously, the reaction proceeds smoothly in water as a solvent and neither organic ligands nor inert atmosphere are required. PMID- 22058577 TI - NHC-catalyzed dehydrogenative self-coupling of diphenylsilane: A facile synthesis of octaphenylcyclotetra(siloxane). AB - A unique application of the CuIPr N-heterocyclic carbene (NHC) to the dehydrogenative self-coupling of diphenylsilane has been discovered. This transformation is carried out open to air at room temperature, yielding octaphenylcyclotetra(siloxane) quantitatively in one hour. This preparation constitutes a significant improvement over existing methods for the preparation of this compound and demonstrates a novel mode of reactivity for CuIPr. The diphenylsilanone tetramer is the precursor to a number of industrially significant polymers. PMID- 22058579 TI - ToF-SIMS imaging and depth profiling of HeLa cells treated with bromodeoxyuridine. AB - Time of flight secondary ion mass spectrometry 2D images and molecular depth profiles of human HeLa cells treated with bromodeoxyuridine (BrdU) were acquired in the dual beam mode (Bi(3) (+) analysis beam, C(60) (+) etching beam). Several preparation protocols were investigated and were compared to a simple wash-and dry method. The feasibility of using C(60) to clean the samples prior to imaging with Bi was also investigated quantitatively by calibrating full depth profiles of the cells using atomic force microscopy. BrdU was used as a marker for the cell nucleus, facilitating identification and localization of sub-cellular features during depth profiling. Results show that C(60) can be used to remove the surface contamination and to access different layers within the cells for 2D imaging. For a 1 nA, 10 keV C(60) (+) beam incident at 45 degrees and rastered over a 500 * 500 MUm(2) area, ~1 nm of biological material was sputtered every second. Our results show that HeLa cells were completely removed after etching with 1.3*10(15) C(60) (+) ions per cm(2), giving an average etching rate of 3.9 nm for every 10(13) C(60) per cm(2) at 10 keV and 45 degrees incidence. PMID- 22058580 TI - Sampling in Qualitative Research: Rationale, Issues, and Methods. AB - In gerontology the most recognized and elaborate discourse about sampling is generally thought to be in quantitative research associated with survey research and medical research. But sampling has long been a central concern in the social and humanistic inquiry, albeit in a different guise suited to the different goals. There is a need for more explicit discussion of qualitative sampling issues. This article will outline the guiding principles and rationales, features, and practices of sampling in qualitative research. It then describes common questions about sampling in qualitative research. In conclusion it proposes the concept of qualitative clarity as a set of principles (analogous to statistical power) to guide assessments of qualitative sampling in a particular study or proposal. PMID- 22058578 TI - Natural and Genetically Engineered Proteins for Tissue Engineering. AB - To overcome the limitations of traditionally used autografts, allografts and, to a lesser extent, synthetic materials, there is the need to develop a new generation of scaffolds with adequate mechanical and structural support, control of cell attachment, migration, proliferation and differentiation and with bio resorbable features. This suite of properties would allow the body to heal itself at the same rate as implant degradation. Genetic engineering offers a route to this level of control of biomaterial systems. The possibility of expressing biological components in nature and to modify or bioengineer them further, offers a path towards multifunctional biomaterial systems. This includes opportunities to generate new protein sequences, new self-assembling peptides or fusions of different bioactive domains or protein motifs. New protein sequences with tunable properties can be generated that can be used as new biomaterials. In this review we address some of the most frequently used proteins for tissue engineering and biomedical applications and describe the techniques most commonly used to functionalize protein-based biomaterials by combining them with bioactive molecules to enhance biological performance. We also highlight the use of genetic engineering, for protein heterologous expression and the synthesis of new protein based biopolymers, focusing the advantages of these functionalized biopolymers when compared with their counterparts extracted directly from nature and modified by techniques such as physical adsorption or chemical modification. PMID- 22058581 TI - Parallelization of Nullspace Algorithm for the computation of metabolic pathways. AB - Elementary mode analysis is a useful metabolic pathway analysis tool in understanding and analyzing cellular metabolism, since elementary modes can represent metabolic pathways with unique and minimal sets of enzyme-catalyzed reactions of a metabolic network under steady state conditions. However, computation of the elementary modes of a genome- scale metabolic network with 100 1000 reactions is very expensive and sometimes not feasible with the commonly used serial Nullspace Algorithm. In this work, we develop a distributed memory parallelization of the Nullspace Algorithm to handle efficiently the computation of the elementary modes of a large metabolic network. We give an implementation in C++ language with the support of MPI library functions for the parallel communication. Our proposed algorithm is accompanied with an analysis of the complexity and identification of major bottlenecks during computation of all possible pathways of a large metabolic network. The algorithm includes methods to achieve load balancing among the compute-nodes and specific communication patterns to reduce the communication overhead and improve efficiency. PMID- 22058582 TI - Dirichlet Component Regression and its Applications to Psychiatric Data. AB - We describe a Dirichlet multivariable regression method useful for modeling data representing components as a percentage of a total. This model is motivated by the unmet need in psychiatry and other areas to simultaneously assess the effects of covariates on the relative contributions of different components of a measure. The model is illustrated using the Positive and Negative Syndrome Scale (PANSS) for assessment of schizophrenia symptoms which, like many other metrics in psychiatry, is composed of a sum of scores on several components, each in turn, made up of sums of evaluations on several questions. We simultaneously examine the effects of baseline socio-demographic and co-morbid correlates on all of the components of the total PANSS score of patients from a schizophrenia clinical trial and identify variables associated with increasing or decreasing relative contributions of each component. Several definitions of residuals are provided. Diagnostics include measures of overdispersion, Cook's distance, and a local jackknife influence metric. PMID- 22058584 TI - What is New in the "New Rural Co-operative Medical System"? An Assessment in One Kazak County of the Xinjiang Uyghur Autonomous Region. AB - In 2002, the Chinese leadership announced a change in national welfare policy: Voluntary medical schemes at county level, called the "New Rural Co-operative Medical System" should cover all counties by 2010. This article addresses the main characteristics of this system, analyses the introduction of local schemes based on our own field studies in one Kazak county of the Xinjiang Uyghur Autonomous Region since 2006, and argues that the fast progressing of the local scheme and the flexibility shown by local administrators in considering structural and procedural adjustments are not the result of central directives but of local initiatives. Recentralization from the township governments to functional departments in the provincial and the central state administration is only one aspect of current rural governance. Complementary forms of locally embedded responsiveness to the needs of health care recipients are crucial in restructuring the administration and discharge of health care. These new modes of governance are different from the hierarchical control and institutionalized representation of interests of the local population. PMID- 22058585 TI - Raman spectroscopy as a potentialmethod for the detection of extremely halophilic archaea embedded in halite in terrestrial and possibly extraterrestrial samples. AB - Evidence for the widespread occurrence of extraterrestrial halite, particularly on Mars, has led to speculations on the possibility of halophilic microbial forms of life; these ideas have been strengthened by reports of viable haloarchaea from sediments of geological age (millions of years). Raman spectroscopy, being a sensitive detection method for future astrobiological investigations onsite, has been used in the current study for the detection of nine different extremely halophilic archaeal strains which had been embedded in laboratory-made halite crystals in order to simulate evaporitic conditions. The cells accumulated preferentially in tiny fluid inclusions, in simulation of the precipitation of salt in natural brines. FT-Raman spectroscopy using laser excitation at 1064 nm and dispersive micro Raman spectroscopy at 514.5 nm were applied. The spectra showed prominent peaks at 1507, 1152 and 1002 cm(-1) which are attributed to haloarchaeal C(50) carotenoid compounds (mainly bacterioruberins). Their intensity varied from strain to strain at 1064-nm laser excitation. Other distinguishable features were peaks due to peptide bonds (amide I, amide III) and to nucleic acids. No evidence for fatty acids was detected, consistent with their general absence in all archaea.These results contribute to a growing database on Raman spectra of terrestrial microorganisms from hypersaline environments and highlight the influence of the different macromolecular composition of diverse strains on these spectra. PMID- 22058586 TI - Autologous fat injection to face and neck: from soft tissue augmentation to regenerative medicine. AB - Minimally-invasive autologous fat injection of the head and neck region can be considered a valid alternative to major invasive surgical procedures both for aesthetic and functional purposes. The favourable outcomes of autologous fat injection in otolaryngological practice are due to the filling of soft tissue and, mainly, to the potential regenerative effect of adipose-derived mesenchymal stem cells. Herewith, some important biological preliminary remarks are described underlying the potential of autologous fat injection in regenerative medicine, and personal experience in using it for both consolidated clinical applications, such as fat grafting to the face and vocal fold augmentation in the treatment of glottic incompetence, and more recent applications including the treatment of post-parotidectomy Frey syndrome and velopharyngeal insufficiency. PMID- 22058587 TI - Management of acute idiopathic sensorineural hearing loss: a survey of UK ENT consultants. AB - Acute sensorineural hearing loss is a rare event. As yet, there is no standard agreed treatment of this condition because there appears to be little reliable evidence that any one treatment will improve the hearing in these cases. This postal questionnaire was conducted to ascertain the current management of unilateral, acute, idiopathic sensorineural hearing loss by ENT consultants in the UK to see if there is at least a consensus of approach which might lay the foundation for an agreed treatment. Approximately 60% of consultants would admit a patient presenting with these symptoms and only 2% would not prescribe any form of treatment. Of those who do treat the patient, virtually all (99.2%) would prescribe steroids. PMID- 22058588 TI - Caloric stimulation with near infrared radiation does not induce paradoxical nystagmus. AB - Near infrared radiation can be used for warm stimulation in caloric irrigation of the equilibrium organ. Aim of this study was to determine whether near infrared radiation offers effective stimulation of the vestibular organ, whether it is well tolerated by the patients and especially whether it is a viable alternative to warm air stimulation in patients with defects of the tympanic membrane and radical mastoid cavities. Patients with perforations of the tympanic membrane (n = 15) and with radical mastoid cavities (n = 13) were tested both with near infrared radiation and warm dry air. A caloric-induced nystagmus could be seen equally effectively and rapidly in all patients. Contrary to stimulation with warm dry air, no paradoxical nystagmus was observed following caloric irrigation with a warm stimulus (near infrared radiation). Results of a questionnaire showed excellent patient acceptance of near infrared stimulation with no arousal effects or unpleasant feeling. In conclusion, near infrared radiation proved to be an alternative method of caloric irrigation to warm dry air in patients with tympanic membrane defects and radical mastoid cavities. Near infrared radiation is pleasant, quick, contact free, sterile and quiet. With this method an effective caloric warm stimulus is available. If near infrared radiation is used for caloric stimulus no evaporative heat loss occurs. PMID- 22058590 TI - Status of level IIb lymph nodes of the neck in squamous cell carcinoma of the oral tongue in patients who underwent modified radical neck dissection and lymph node sentinel biopsy. AB - Status of lymph nodes of level IIb was examined to identify the incidence of nodal metastasis and the lymphatic drainage in squamous cell carcinoma of the oral tongue in patients undergoing modified radical neck dissection (MRND) and sentinel node biopsy (SNB). Overall, 72 patients were divided into two groups; 38 patients (Group A) of any T and N+ or T3-T4- N0 stage underwent MRND. The surgical specimens were sent to the Pathology Department, divided into specific levels (I, IIa, IIb, III, IV, V) and labelled. The remaining 34 patients (Group B) T1-T2 -N0 stage were submitted to SNB. The histological examination of the specimens of the two groups was performed by staining with haematoxylin and eosin several sections from each node at different levels and then using a molecular marker such as cytokeratin and Epithelial Membrane Antigen (EMA). In Group A: In N0 there were no occult metastases at level IIb; in N+ neck, 8 cases (33.3%) showed metastasis at level IIb (P = 0.04). Metastases at level IIb were observed only in combination with other levels (P = 0.03). In Group B, direct lymphatic drainage was found in 2 patients (5.9%) at level IIb. There were no occult metastases at level IIb. Out of the 54 sentinel nodes harvested, 4 lymph nodes (7.4%) were found to be metastatic; these 4 sentinel nodes were found respectively in 4 patients, 1 at level III, 3 at level II a with an occult metastasis rate of 11.7%. In conclusion, SNB has prospected a new concept of lymphatic drainage that is variable and individual. SNB has demonstrated that direct lymphatic drainage is possible to level II b. In our experience with early cancer of the tongue (T1-T2 NO ), SNB aided with lympho-scintigraphy seems to be a good technique for staging the neck with minimal morbidity. PMID- 22058591 TI - Clinical approach and treatment of benign and malignant parotid masses, personal experience. AB - Parotid gland tumours account for 80% of all salivary gland neoplasms, 20% of these are malignant, but in daily clinical practice most parotid masses are operated on before obtaining the final histological diagnosis. This clinical setting further complicates the critical point of parotid surgery, which is the management of the facial nerve. In the present study, data were evaluated referring to 540 patients who underwent parotidectomy for a mass which was discovered to be a benign (470 cases) or a malignant (70 cases) neoplasm, between November 1994 and December 2007, at our Institution. The most significant single parameter in this series of malignancies regarding disease specific survival was the clinical involvement of the facial nerve at diagnosis (p = 0.006). Also for this reason, as there is no evidence that liberal VIIth nerve sacrifice improves prognosis, when it is not clinically involved, every attempt is made to dissect and preserve it. At present, the most complicated situation concerning nerve preservation may be, on the other hand, recurrence of a benign tumour, in particular pleomorphic adenoma, which, in our series, has a higher incidence (8.3%) of permanent facial dysfunction, than surgery with nerve preservation for malignancy (3.7%). PMID- 22058592 TI - Diagnostic and therapeutic iter in paediatric OSAS: personal experience. AB - Obstructive sleep apnoea syndrome in a child is characterized by prolonged episodes of obstructive hypopnoea and/or apnoea of upper airway leading to morbidity. The most common risk factor is adeno-tonsillar hypertrophy. Obstructive sleep apnoea syndrome diagnosis is based on clinical ENT evaluation and an instrumental approach, such as pulse oximetry or the gold standard overnight polysomnography. The aim is to establish, in a population of children with suspected obstructive sleep apnoea syndrome, the frequency of this disorder, the effect of adenotonsillectomy and the risk of post-operative complications. A total of 481 patients (297 male, 184 female) with suspected obstructive sleep apnoea syndrome (aged 2-14 years) were evaluated between March 2007 and April 2010 and divided into 3 morphological phenotypes: classic, adult and congenital. All patients underwent ENT assessment and a pulse oximetry with 4 channels cardiopulmonary monitoring. The examination following the Brouillette criteria was defined as negative, positive or inconclusive; when positive, adenotonsillectomy was the first therapeutic approach. At 6 months after surgery, all patients underwent check-up pulse oximetry. Of the overall sample, 96% of the patients had a classical phenotype, 3% an adult type and 1% a congenital type. The monitoring resulted pathological in 19% (17% of them were at increased post operative risk), negative in 61% and inconclusive in 20%. All 5 patients with congenital phenotype were positive. Of the positive patients, 86% underwent adenotonsillectomy and a control pulse oximetry 6 months thereafter, 96% resulted negative. Pulse oximetry was efficient in order to avoid incorrect surgery indications, improving appropriateness and safety of adenotonsillectomy in children with obstructive sleep apnoea syndrome. Adenotonsillectomy showed a success rate of 96% and there were no episodes of post-surgery complications in particular in those patients at increased risk. PMID- 22058593 TI - About muscle insertions in man (Proposal for a new nomenclature of striated muscle). AB - Some plastic surgeons are limited in their technical knowledge on the mimetic muscle and conversely appear to vindicate a distinct priority in the problem of surgical rejuvenation, or, in general, in the effects of ageing, always involving the mimetic muscles included in the skin. Anatomists have worked better in research on mimetic muscles that we would like to indicate as not inserted, free to move in a different way from that of inserted or semi-inserted. Otolaryngologists and maxillo-facial surgeons, in the practice of surgery on the salivary glands, seem to have studied mimetic muscles before and in more detailed manner than plastic surgeons. PMID- 22058594 TI - Basaloid squamous cell carcinoma of the larynx: report of a early laryngeal cancer. AB - Basaloid squamous cell carcinoma is a recently recognized, rare and aggressive variant of squamous cell carcinoma with a predilection to occur in base of the tongue, hypopharynx and larynx (especially the supraglottic tract). It is usually diagnosed in advanced stage, frequently with distant metastases, requiring aggressive surgical intervention. The prognosis is remarkably poor even after the association of radiotherapy or chemotherapy. Nevertheless recently it has been reported that in the early stage this neoplasm seems to have a behaviour less aggressive, similar to conventional squamous carcinoma. The therapeutic approach is not clearly defined when the neoplasm is diagnosed at an early stage. We present a case of early stage of basaloid squamous cell carcinoma of the supraglottic larynx. PMID- 22058595 TI - Granular cell tumour of the tongue in a 14-year-old boy: case report. AB - Granular cell tumour is a rare soft tissue neoplasm that can virtually affect any site of the body. Its histological origin is controversial, since several studies have shown that different cells are involved. Granular cell tumour was initially described as myoblastoma, but, at present, a neural origin is supported by most Authors, due to the immunohistochemical pattern. Even if the biological behaviour of granular cell tumours is usually benign, accurate histological examination is mandatory, because in a small number of cases they can be malignant. Here, a case is described of granular cell tumour in a 14-year-old boy, which is a very rare occurrence, since these tumours typically manifest in subjects between the third and sixth decade. Histopathological features, differential diagnosis and therapeutic implications of granular cell tumour are discussed, together with a brief review of the recent literature. PMID- 22058596 TI - Bilateral deep neck space infection in the paediatric age group: a case report and review of the literature. AB - Deep neck space infections can occur at any age but require more intimate management in the paediatric age group because of their rapidly progressive nature. Concurrent abscess in distinct neck spaces has rarely been reported in healthy children. Herewith, a rare case of bilateral neck abscess is reported in a 16-month-old female and the clinical presentation and management are discussed with a review of the literature. PMID- 22058597 TI - Primary haemangiopericytoma of the parapharyngeal space: an unusual tumour and review of the literature. AB - Haemangiopericytoma is a rare soft tissue tumour, with great histological variability and unpredictable clinical and biological behaviour. The precise cell type origin is uncertain. One third of haemangiopericytomas occur in the head and neck area, but only a few cases have been reported regarding localization at the parapharyngeal space. Herewith, case is presented of a 54-year-old female, referred to our Department due to a parapharyngeal space tumour with non-specific imaging characteristics. The patient underwent radical excision of the tumour with a trans-cervical sub-mandibular approach. The histolopathologic examination revealed a neoplasm with the characteristic features of haemangiopericytoma. One year later, during the scheduled follow-up, the computerized tomography scan showed no evidence of recurrence or residual disease. The pre-operative evaluation of a haemangiopericytoma must include a thorough imaging evaluation with computerized tomography and magnetic resonance imaging, even if results may not be specific for haemangiopericytoma. Angiography and pre-operative embolization may be performed in cases of large tumours with significant vascularity. The treatment of choice is radical excision. The follow-up includes clinical evaluation every 6 months and annual magnetic resonance imaging for at least 3 years. PMID- 22058598 TI - Letter from Editor-in-Chief. PMID- 22058599 TI - Effectiveness and pitfalls of elective neck dissection in N0 laryngeal cancer. AB - The aim of the study was to evaluate the efficacy and potential pitfalls of selective neck dissection of levels II-IV in controlling occult neck disease in clinically negative neck (cN0) of patients with laryngeal squamous cell carcinoma. Charts of 96 consecutive cN0 laryngeal cancer patients undergoing 122 neck dissections at the University of Florence from January 2000 to December 2004 were reviewed. N0 neck was defined with contrast enhanced computed tomography scan. Occult neck disease rate was 12.5%, involvement per level was: 47.6% at level II, 38.1% at level III, 9.5% at level IV. Six patients developed neck recurrence (6.25%) after selective neck dissection of levels II-IV within the first two years after treatment. In conclusion, selective neck dissection of levels II-IV is effective in N0 laryngeal squamous cell carcinoma; posterior limits of surgical resection are missing therefore if post-operative radiation is required, the field should be extended beyond the dissected levels. The low incidence of occult neck disease indicates the need to refine treatment strategy, restricting elective neck dissection only to supraglottic T2 with epilaryngeal involvement, supraglottic T3-4 and glottic T4 tumours, and considering a "wait and see" protocol implemented with imaging techniques and cytological assessments for other lesions. PMID- 22058600 TI - Transnasal endoscopic removal of malformation of the odontoid process in a patient with type I Arnold-Chiari malformation: a case report. AB - The endoscopic endonasal approach is emerging as a feasible alternative to the trans-oral route for the resection of the odontoid process, when the latter produces a compression of the brainstem and cervicomedullary junction. This type of approach has some advantages, such as excellent pre-vertebral exposure of the cranio-vertebral junction in patients with small oral cavities and the possibility to avoid the use of mouth retractors. A typical case of a 24-year-old male patient with a previous diagnosis of type I Arnold-Chiari Malformation, suffering from a posterior dislocation of the odontoid process causing severe anterior compression of the brainstem, is presented to stress the potential of this technique. Trans-nasal endoscopic removal of the odontoid process was performed and resolution of the ventral compression of the brainstem was achieved. This report demonstrates that in selected cases, an endoscopic endonasal approach should now be considered an excellent alternative to the traditional trans-oral approach. PMID- 22058601 TI - Bilateral SMAS rhytidectomy in parotid recurrent pleomorphic adenoma. AB - A case is presented of a young female with parotid recurrent pleomorphic adenoma and skin infiltration treated with subtotal parotidectomy combined with a bilateral superficial muscular aponeurotic system rhytidectomy. PMID- 22058602 TI - Intermarriage and the Intergenerational Transmission of Ethnic Identity and Human Capital for Mexican Americans. AB - We investigate whether selective intermarriage and endogenous ethnic identification interact to hide some of the intergenerational progress achieved by the Mexican-origin population in the United States. In part, we do this by comparing an "objective" indicator of Mexican descent (based on the countries of birth of the respondent and his parents and grandparents) with the standard "subjective" measure of Mexican self-identification (based on the respondent's answer to the Hispanic origin question). For third-generation Mexican-American youth, we show that ethnic attrition is substantial and could produce significant downward bias in standard measures of attainment which rely on ethnic self identification. PMID- 22058603 TI - THE DEFENSIVE NATURE OF BENEFIT FINDING DURING ONGOING TERRORISM: AN EXAMINATION OF A NATIONAL SAMPLE OF ISRAELI JEWS. AB - A study examining the effects of terrorism on a national sample of 1,136 Jewish adults was conducted in Israel via telephone surveys, during the Second Intifada. The relationship between reports of positive changes occurring subsequent to terrorism exposure (i.e., Benefit finding), posttraumatic stress disorder (PTSD) symptom severity, and negative outgroup attitudes toward Palestinian citizens of Israel (PCI) was examined. Benefit finding was related to greater PTSD symptom severity. Further, Benefit finding was related to greater threat perception of PCI and ethnic exclusionism of PCI. Findings were consistent with hypotheses derived from theories of outgroup bias and support the anxiety buffering role of social affiliation posited by terror management theory. This study suggests that benefit finding may be a defensive coping strategy when expressed under the conditions of ongoing terrorism and external threat. PMID- 22058604 TI - Factor Structure Validation of the Alcohol Dependence Scale in a Heavy Drinking College Sample. AB - The prevalence of alcohol use disorders in college students necessitates that adequate measures exist to assess students for abuse and dependence. The Alcohol Dependence Scale (ADS) is a continuous measure of the severity of alcohol involvement found to have a unidimensional factor structure in clinical samples. The latent factor structure of the ADS in college drinkers has not been examined and this study sought to replicate unidimensionality. Heavy college drinkers (N=343) completed the ADS. Performance was examined using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). The CFA did not support a single factor solution. Follow-up EFA revealed a two factor structure. The first, termed "Acute Excessive Drinking" consisted of relatively commonly endorsed items relating to loss of behavioral control, blackouts, and obsessive/compulsive drinking. The second, termed "Severe Withdrawal Symptoms," consisted of relatively infrequently endorsed items relating to withdrawal symptoms. The ADS does not appear to have the same factor structure in college and clinical samples, making it inadvisable as a linear measure of alcohol problems within a college population. PMID- 22058605 TI - Psychosocial Consequences of Intimate Partner Violence (IPV) Exposure in Maltreated Adolescents: Assessing More than IPV Occurrence. AB - The majority of research on the psychosocial impact of intimate partner violence (IPV) exposure for children has focused on IPV occurrence. The current study extended this research by examining three dimensions of IPV exposure: frequency, proximity, and severity, and tested whether these dimensions predicted variance in adolescents' psychosocial problems over-and-above that accounted for by IPV occurrence. Participants included 140 adolescents and their caregivers, who were recruited for an intervention involving maltreated youth placed in out-of-home care. After controlling for IPV occurrence, exposure to community violence, and severity of maltreatment, results indicated a positive association between the multidimensional IPV index and youth report of psychosocial problems. There was also a trend for a positive association between the IPV index and caregiver report of psychosocial problems for boys. The study's results are discussed in terms of their implications for prevention researchers and child welfare agencies. PMID- 22058606 TI - Food composition database harmonization for between-country comparisons of nutrient data in the TEDDY Study. AB - The Environmental Determinants of Diabetes in the Young Study (TEDDY) aims at examining the associations between islet autoimmunity and various environmental exposures, (e.g. diet) in Finland, Germany, Sweden and the United States (US). In order to produce comparable results from dietary assessments, the national food composition databases (FCDB) must contain mutually comparable food composition data. Systematic comparison (definition, unit of measurement, and method of analysis) of energy, protein, fats, carbohydrates, cholesterol, fiber, 13 vitamins, and 8 minerals was carried out among the FCDB of the four countries. Total fat, cholesterol, vitamin A: retinol equivalents and beta-carotene, thiamin, riboflavin, pyridoxine, vitamin B(12), calcium, phosphorus, potassium, magnesium, iron, and zinc are comparable across all four databases. Carbohydrates, fiber, sugars, fatty acids, vitamin D, vitamin E: alpha tocopherol, vitamin K, vitamin C, pantothenic acid, niacin, manganese, and copper are comparable or can be converted comparable at least across three of the databases. Vitamin E: alpha-tocopherol equivalents, will be comparable across all databases after Finland and Germany subtract tocotrienols from their values. Nitrogen values were added to the Swedish and US databases. After recalculation of protein from nitrogen (Sweden and US), and subtraction of fiber from the total carbohydrate (Finland) followed by recalculations of energy, these values will be comparable across the countries. Starch and folate are not comparable. PMID- 22058607 TI - COMPARING THE IMPAIRMENT PROFILES OF OLDER DRIVERS AND NON-DRIVERS: TOWARD THE DEVELOPMENT OF A FITNESS-TO-DRIVE MODEL. AB - The purpose of this research effort was to compare older driver and non-driver functional impairment profiles across some 60 assessment metrics in an initial effort to contribute to the development of fitness-to-drive assessment models. Of the metrics evaluated, 21 showed statistically significant differences, almost all favoring the drivers. Also, it was shown that a logistic regression model comprised of five of the assessment scores could completely and accurately separate the two groups. The results of this study imply that older drivers are far less functionally impaired than non-drivers of similar ages, and that a parsimonious model can accurately assign individuals to either group. With such models, any driver classified or diagnosed as a non-driver would be a strong candidate for further investigation and intervention. PMID- 22058608 TI - Wear Performance of Laser Processed Tantalum Coatings. AB - This first generation investigation evaluates the in vitro tribological performance of laser-processed Ta coatings on Ti for load-bearing implant applications. Linear reciprocating wear tests in simulated body fluid showed one order of magnitude less wear rate, of the order of 10(-4)mm(3)(N.m)(-1), for Ta coatings compared to Ti. Our results demonstrate that Ta coatings can potentially minimize the early-stage bone-implant interface micro-motion induced wear debris generation due to their excellent bioactivity comparable to that of hydroxyapatite (HA), high wear resistance and toughness compared to popular HA coatings. PMID- 22058609 TI - Hydraulic efficiency compromises compression strength perpendicular to the grain in Norway spruce trunkwood. AB - The aim of this study was to investigate bending stiffness and compression strength perpendicular to the grain of Norway spruce (Picea abies (L.) Karst.) trunkwood with different anatomical and hydraulic properties. Hydraulically less safe mature sapwood had bigger hydraulic lumen diameters and higher specific hydraulic conductivities than hydraulically safer juvenile wood. Bending stiffness (MOE) was higher, whereas radial compression strength lower in mature than in juvenile wood. A density-based tradeoff between MOE and hydraulic efficiency was apparent in mature wood only. Across cambial age, bending stiffness did not compromise hydraulic efficiency due to variation in latewood percent and because of the structural demands of the tree top (e.g. high flexibility). Radial compression strength compromised, however, hydraulic efficiency because it was extremely dependent on the characteristics of the "weakest" wood part, the highly conductive earlywood. An increase in conduit wall reinforcement of earlywood tracheids would be too costly for the tree. Increasing radial compression strength by modification of microfibril angles or ray cell number could result in a decrease of MOE, which would negatively affect the trunk's capability to support the crown. We propose that radial compression strength could be an easily assessable and highly predictive parameter for the resistance against implosion or vulnerability to cavitation across conifer species, which should be topic of further studies. PMID- 22058610 TI - Photonic Shell-Crosslinked Nanoparticle Probes for Optical Imaging and Monitoring. AB - A pH-insensitive fluorophore is made to give pH-driven responses through its covalent incorporation within a nanostructure derived from pH-responsive polymers. Fluorophore-shell-crosslinked nanoparticles (SCKs) demonstrate notable enhancement of photophysical properties, in the physiological pH region. Fluorophore-SCKs are designed to swell at higher pH and shrink as the pH is lowered, producing high fluorescence vs. low fluorescence outputs, respectively. PMID- 22058611 TI - Extent and implications of the academia-industry connection. PMID- 22058612 TI - Of money and trust in biomedical care. PMID- 22058613 TI - Academia, journal publishing and the bio-medical industry. PMID- 22058615 TI - Footprints to follow. PMID- 22058614 TI - The ICMJE and URM: Providing Independent Advice for the Conduct of Biomedical Research and Publication. AB - The International Committee of Medical Journal Editors (ICMJE) is a working group of editors of selected medical journals that meets annually. Founded in Vancouver, Canada, in 1978, it currently consists of 11 member journals and a representative of the US National Library of Medicine. The major purpose of the Committee is to address and provide guidance for the conduct and publishing of biomedical research and the ethical tenets underpinning these activities. This advice is detailed in the Committee's Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication (URM).Recently, the ICMJE has adopted an interventionist role to ensure transparency of conflict of interest revelations in the conduct and publication of industry supported research. It also pursues a policy for the lodgement with trial registries of specified details of Phase III clinical trials. Failure to comply would jeopardise publication of trial outcomes in ICMJE member journals. This policy has resulted in the coming on stream of trial registries, international agreement on trial minimal datasets and compliance with trial registration requirements. PMID- 22058616 TI - Guidelines, editors, pharma and the biological paradigm shift. AB - Private investment in biomedical research has increased over the last few decades. At most places it has been welcomed as the next best thing to technology itself. Much of the intellectual talent from academic institutions is getting absorbed in lucrative positions in industry. Applied research finds willing collaborators in venture capital funded industry, so a symbiotic growth is ensured for both.There are significant costs involved too. As academia interacts with industry, major areas of conflict of interest especially applicable to biomedical research have arisen. They are related to disputes over patents and royalty, hostile encounters between academia and industry, as also between public and private enterprise, legal tangles, research misconduct of various types, antagonistic press and patient-advocate lobbies and a general atmosphere in which commercial interest get precedence over patient welfare.Pharma image stinks because of a number of errors of omission and commission. A recent example is suppression of negative findings about Bayer's Trasylol (Aprotinin) and the marketing maneuvers of Eli Lilly's Xigris (rhAPC). Whenever there is a conflict between patient vulnerability and profit motives, pharma often tends to tilt towards the latter. Moreover there are documents that bring to light how companies frequently cross the line between patient welfare and profit seeking behaviour.A voluntary moratorium over pharma spending to pamper drug prescribers is necessary. A code of conduct adopted recently by OPPI in India to limit pharma company expenses over junkets and trinkets is a welcome step.Clinical practice guidelines (CPG) are considered important as they guide the diagnostic/therapeutic regimen of a large number of medical professionals and hospitals and provide recommendations on drugs, their dosages and criteria for selection. Along with clinical trials, they are another area of growing influence by the pharmaceutical industry. For example, in a relatively recent survey of 2002, it was found that about 60% of 192 authors of clinical practice guidelines reported they had financial connections with the companies whose drugs were under consideration. There is a strong case for making CPGs based not just on effectivity but cost effectivity. The various ramifications of this need to be spelt out. Work of bodies like the Appraisal of Guidelines Research and Evaluation (AGREE) Collaboration and Guidelines Advisory Committee (GAC) are also worth a close look.Even the actions of Foundations that work for disease amelioration have come under scrutiny. The process of setting up 'Best Practices' Guidelines for interactions between the pharmaceutical industry and clinicians has already begun and can have important consequences for patient care. Similarly, Good Publication Practice (GPP) for pharmaceutical companies have also been set up aimed at improving the behaviour of drug companies while reporting drug trialsThe rapidly increasing trend toward influence and control by industry has become a concern for many. It is of such importance that the Association of American Medical Colleges has issued two relatively new documents - one, in 2001, on how to deal with individual conflicts of interest; and the other, in 2002, on how to deal with institutional conflicts of interest in the conduct of clinical research. Academic Medical Centers (AMCs), as also medical education and research institutions at other places, have to adopt means that minimize their conflicts of interest.Both medical associations and research journal editors are getting concerned with individual and institutional conflicts of interest in the conduct of clinical research and documents are now available which address these issues. The 2001 ICMJE revision calls for full disclosure of the sponsor's role in research, as well as assurance that the investigators are independent of the sponsor, are fully accountable for the design and conduct of the trial, have independent access to all trial data and control all editorial and publication decisions. However the findings of a 2002 study suggest that academic institutions routinely participate in clinical research that does not adhere to ICMJE standards of accountability, access to data and control of publication.There is an inevitable slant to produce not necessarily useful but marketable products which ensure the profitability of industry and research grants outflow to academia. Industry supports new, not traditional, therapies, irrespective of what is effective. Whatever traditional therapy is supported is most probably because the company concerned has a product with a big stake there, which has remained a 'gold standard' or which that player thinks has still some 'juice' left.Industry sponsorship is mainly for potential medications, not for trying to determine whether there may be non-pharmacological interventions that may be equally good, if not better. In the paradigm shift towards biological psychiatry, the role of industry sponsorship is not overt but probably more pervasive than many have realised, or the right thinking may consider good, for the health of the branch in the long run.An issue of major concern is protection of the interests of research subjects. Patients agree to become research subjects not only for personal medical benefit but, as an extension, to benefit the rest of the patient population and also advance medical research.We all accept that industry profits have to be made, and investment in research and development by the pharma industry is massive. However, we must also accept there is a fundamental difference between marketing strategies for other entities and those for drugs.The ultimate barometer is patient welfare and no drug that compromises it can stand the test of time. So, how does it make even commercial sense in the long term to market substandard products? The greatest mistake long-term players in industry may make is try to adopt the shady techniques of the upstart new entrant. Secrecy of marketing/sales tactics, of the process of manufacture, of other strategies and plans of business expansion, of strategies to tackle competition are fine business tactics. But it is critical that secrecy as a tactic not extend to reporting of research findings, especially those contrary to one's product.Pharma has no option but to make a quality product, do comprehensive adverse reaction profiles, and market it only if it passes both tests.Why does pharma adopt questionable tactics? The reasons are essentially two:What with all the constraints, a drug comes to the pharmacy after huge investments. There are crippling overheads and infrastructure costs to be recovered. And there are massive profit margins to be maintained. If these were to be dependent only on genuine drug discoveries, that would be taking too great a risk.Industry players have to strike the right balance between profit making and credibility. In profit making, the marketing champions play their role. In credibility ratings, researchers and paid spokes-persons play their role. All is hunky dory till marketing is based on credibility. When there is nothing available to make for credibility, something is projected as one and marketing carried out, in the calculated hope that profits can accrue, since profit making must continue endlessly. That is what makes pharma adopt even questionable means to make profits.Essentially, there are four types of drugs. First, drugs that work and have minimal side-effects; second, drugs which work but have serious side-effects; third, drugs that do not work and have minimal side-effects; and fourth, drugs which work minimally but have serious side-effects. It is the second and fourth types that create major hassles for industry. Often, industry may try to project the fourth type as the second to escape censure.The major cat and mouse game being played by conscientious researchers is in exposing the third and fourth for what they are and not allowing industry to palm them off as the first and second type respectively. The other major game is in preventing the second type from being projected as the first. The third type are essentially harmless, so they attract censure all right and some merriment at the antics to market them. But they escape anything more than a light rap on the knuckles, except when they are projected as the first type.What is necessary for industry captains and long-term players is to realise:Their major propelling force can only be producing the first type. 2. They accept the second type only till they can lay their hands on the first. 3. The third type can be occasionally played around with to shore up profits, but never by projecting them as the first type. 4. The fourth type are the laggards, real threat to credibility and therefore do not deserve any market hype or promotion.In finding out why most pharma indulges in questionable tactics, we are lead to some interesting solutions to prevent such tactics with the least amount of hassles for all concerned, even as both profits and credibility are kept intact. PMID- 22058617 TI - The image of pharma. PMID- 22058618 TI - Clinical practice guidelines and industry. PMID- 22058619 TI - Guideline standardisation, cost effectiveness, industry needs and conflict of interest. PMID- 22058620 TI - Foundations and task forces. PMID- 22058621 TI - Concerned Journals, Editors And ICMJE. PMID- 22058622 TI - Ethical obligation towards research subjects. PMID- 22058623 TI - Useful and marketable, new and traditional. PMID- 22058624 TI - Biological psychiatry, research and industry. PMID- 22058625 TI - What propels the pharma industry? PMID- 22058626 TI - Concluding remarks. PMID- 22058627 TI - Questions that this monograph raises. PMID- 22058628 TI - What psychoanalysis, culture and society mean to me. AB - The paper reviews some ways that the social and psychic have been understood in psychoanalysis and argues that a model for understanding the relation between the psychic and the social must account both for the ways that we internalize oppressive norms as well as the ways we resist them. The author proposes that we build our identities in relation to other identities circulating in our culture and that cultural hierarchies of sexism, racism, classism push us to split off part of what it means to be human, thereby creating painful individual and relational repetition compulsions. These "normative unconscious processes" replicate the unjust social norms that cause psychic pain in the first place. The paper concludes with thoughts about contemporary US culture, in which the government has abdicated responsibility toward its most vulnerable citizens and has thus rendered vulnerability and dependence shameful states. PMID- 22058629 TI - What the cognitive neurosciences mean to me. AB - Cognitive Neuroscience is an interdisciplinary area of research that combines measurement of brain activity (mostly by means of neuroimaging) with a simultaneous performance of cognitive tasks by human subjects. These investigations have been successful in the task of connecting the sciences of the brain (Neurosciences) and the sciences of the mind (Cognitive Sciences). Advances on this kind of research provide a map of localization of cognitive functions in the human brain. Do these results help us to understand how mind relates to the brain? In my view, the results obtained by the Cognitive Neurosciences lead to new investigations in the domain of Molecular Neurobiology, aimed at discovering biophysical mechanisms that generate the activity measured by neuroimaging instruments. In this context, I argue that the understanding of how ionic/molecular processes support cognition and consciousness cannot be made by means of the standard reductionist explanations. Knowledge of ionic/molecular mechanisms can contribute to our understanding of the human mind as long as we assume an alternative form of explanation, based on psycho-physical similarities, together with an ontological view of mentality and spirituality as embedded in physical nature (and not outside nature, as frequently assumed in western culture). PMID- 22058630 TI - What medical writing means to me. AB - This is a personal account based on many years experience as a medical writer. It considers aspects of medical writing with particular focus on the intellectual and ethical dilemmas it can raise. What makes medical writing both so interesting and so challenging is the fact that it often takes place at the border between different disciplines. For example, it straddles both science and art. Ethical issues also arise at the boundaries between academia and commerce. Until recently there have been few guidelines to help navigate such potentially dangerous territory. I have been privileged to be involved in developing two such guidelines and I describe how I hope the Good Publication Practice guidelines for pharmaceutical companies and the European Medical Writers Association guidelines may improve the practice of this fascinating profession, Medical Writing. PMID- 22058631 TI - What psychiatry means to me. AB - Moving in early career from public health physician to psychiatrist gives me a public health view of psychiatry and an interest in pursuing the goals of widening access to community-based services for people with mental disorders and promoting mental health in communities. Training in social medicine in the UK and psychiatry in Australia lead to studies of homelessness in people living with psychotic disorders, the health of family caregivers, assessing quality of life and mental health promotion.Work with the World Health Organization (WHO) in the Western Pacific Region and the World Psychiatric Association (WPA) worldwide has given me opportunities to work with psychiatrists, mental health workers, service users and others in governments and non-government organisations implementing the recommendations of the World Health Report 2001 in countries with limited resources. My work as WPA Secretary for Publications seeks to improve information exchange in countries irrespective of their wealth. This is an exciting time to be working in a global village with technical capacity to reach into its furthest corners. Psychiatrists supported by WPA can help ensure that vulnerable people and communities and people living with mental disorders are well served in this new environment and no longer left out and left behind. PMID- 22058633 TI - Questions that this paper raises. PMID- 22058632 TI - Recollections of a journey through a psychotic episode: or, mental illness and creativity. PMID- 22058634 TI - A Discussion in the Mensanamonographs e-group. PMID- 22058635 TI - Doctor at work, late evening. PMID- 22058636 TI - Taking care of time. PMID- 22058637 TI - Ravinder lal kapur, m.d. (1938-2006). PMID- 22058638 TI - Open reduction and internal fixation of clavicular nonunions with allograft bone substitute. AB - BACKGROUND: Biologic augmentation with allograft has shown equivalent healing rates to autograft in several nonunion models. No literature exists clearly demonstrating this in the clavicle. The purpose of this study was to evaluate the healing and complication rates of clavicle nonunions treated solely with open reduction and internal fixation (ORIF) and allograft. MATERIALS AND METHODS: Nineteen clavicle nonunions treated with ORIF and allograft were evaluated retrospectively to assess healing rates and complications based on clinical symptoms and radiographic findings. RESULTS: For the 19 patients included and treated with ORIF and allograft, clinical follow-up averaged 15 months. Seven patients were smokers. Although complete radiographic healing was achieved in only 68% of patients, clinical success occurred in 16 (84%) patients who demonstrated full range of motion and strength without pain. The three patients who did not demonstrate full radiographic healing were completely pain free. Five patients experienced complications (26%). Two underwent hardware removal due to persistent irritation after union. Three had a persistent painful nonunion. Each of these three patients was a smoker (P=0.08). Two proceeded to union after revision fixation. The other had hardware failure, which was removed, with a persistent nonunion and did not wish any further treatment. CONCLUSION: ORIF with allograft bone substitute is an acceptable treatment alternative to iliac crest bone graft for clavicle nonunions. However, we did not demonstrate equivalent healing rates to published results utilizing autograft. Smokers were identified to have a trend toward higher failure rates with ORIF augmented with allograft and therefore these patients may be better served by augmenting fixation with autograft. LEVEL OF EVIDENCE: IV; retrospective comparative study. PMID- 22058639 TI - Arthroscopic evaluation and treatment of biceps brachii long head tendon injuries: A survey of the MOON shoulder group. AB - CONTEXT: Injuries to the biceps brachii long head tendon commonly occur in conjunction with tears in the rotator cuff and glenoid labrum. Consensus on treatment of varying levels of severity is undetermined. SETTINGS AND DESIGN: We surveyed members of the Multicenter Orthopedic Outcomes Network (MOON) Shoulder Group, to determine a consensus on arthroscopic grading and treatment. AIMS: We hypothesized that the Lafosse classification system would show a high level of inter- and intraobserver agreement regarding grading/treatment. MATERIALS AND METHODS: Arthroscopic videos of 30 patients determined to have biceps brachii long head tendon injuries were viewed by 13 surgeons. The surgeons graded the severity of the injury macrostructure based on the Lafosse classification system and chose from a list of treatment options. Four months later the same surgeons viewed the same videos and repeated the survey. STATISTICAL ANALYSIS USED: Analysis with weighted and non-weighted Kappa values was performed to determine intra- and interobserver reliability for severity grading and to determine the preferred treatments for each level of severity. RESULTS: Intraobserver reliability testing for the Lafosse system showed substantial agreement after two rounds (81.28%, K=0.7006). Interobserver testing demonstrated substantial agreement for Grade 0 (K=0.7152), fair agreement for Grade 1 (K=0.3803), and moderate agreement for Grade 2 (K=0.5156). Combined responses recommended no surgical treatment for 95.4% of the lesions classified as grade 0 (62/65). No surgical treatment was recommended for Grade 1 lesions in 24.1% of the cases (35/145), debridement in 38.6% (56/145), and tenotomy or tenodesis in 37.2% (54/145). Evaluators preferred tenotomy or tenodesis for 98.3% of the Grade 2 lesions (177/180). CONCLUSIONS: Analysis of the Lafosse system indicated substantial intraobserver reliability for all grades. As Grades 1 and 2 showed only fair and moderate agreement, a need for a reliable grading system still exists. Grade 2 lesions should be treated with tenotomy or tenodesis. A preferred treatment for Grade 1 lesions could not be determined given the high variability of responses. Higher-powered surveys may help determine the ideal treatment of Grade 1 injuries. PMID- 22058640 TI - Combined single photon emission computerized tomography and conventional computerized tomography: Clinical value for the shoulder surgeons? AB - With the cases described, we strive to introduce single photon emission computerized tomography in combination with conventional computer tomography (SPECT/CT) to shoulder surgeons, illustrate the possible clinical value it may offer as new diagnostic radiologic modality, and discuss its limitations. SPECT/CT may facilitate the establishment of diagnosis, process of decision making, and further treatment for complex shoulder pathologies. Some of these advantages were highlighted in cases that are frequently seen in most shoulder clinics. PMID- 22058641 TI - Innovative use of computer-assisted tomography in the management of an irreducible anterior shoulder dislocation. AB - Anterior dislocation of the shoulder is a common injury which is often reduced in the emergency department, without specialist orthopedic input. We report a case of an irreducible locked anterior glenohumeral dislocation with impaction of the humeral head onto the antero-inferior glenoid rim and subsequent generation of a Hill-Sachs lesion. To our knowledge, we describe the first reported case of using computer-assisted tomography to generate a sequence of movements to safely disimpact the locked dislocation without causing further iatrogenic injury or a fracture through the humeral articular surface. This novel image-assisted closed reduction technique spared the patient from the morbidity associated with performing open reduction surgery. At 6-month follow-up, the patient reported no re-dislocations, returned to work and had excellent range of motion. PMID- 22058642 TI - Isolated supraspinatus muscle atrophy and fatty infiltration associated with recurrent anterior shoulder instability: A case report and review of the literature. AB - Supraspinatus muscle atrophy and fatty infiltration are two distinct muscle abnormalities which can be seen after a chronic massive tear or suprascapular neuropathy. Isolated supraspinatus muscle denervation due to suprascapular nerve injury after shoulder dislocation is extremely rare. We report on a patient who developed isolated supraspinatus muscle atrophy and fatty infiltration after traumatic anterior shoulder instability. Possible explanations and etiologies of this rare condition are discussed in this report. PMID- 22058643 TI - From the Editor's Desk. PMID- 22058644 TI - Tamoxifen: An alternative to clomiphene in women with polycystic ovary syndrome. AB - BACKGROUND: Clomiphene citrate is commonly used for ovulation induction in women with anovulatory infertility. However, pregnancy rates with this drug are not as good as ovulation rates. Tamoxifen may be a better choice in some patients who fail to either ovulate or conceive with clomiphene due to its favorable effect on the cervical mucus and endometrium. This study was conducted to evaluate the role of tamoxifen in women with anovulatory infertility and find out the optimum dose needed for achieving the best outcome. MATERIALS AND METHODS: 160 women attending the infertility clinic and suffering from anovulatory infertility were recruited for the study. Tamoxifen was administered in the dose of 40 mg daily and ovulation monitored. In case of anovulation, the dose was increased to 80 mg daily. Ovulation and pregnancy rates were calculated. RESULTS: Twenty-three out of 160 women who received 40 mg of tamoxifen conceived, giving a pregnancy rate of 14.38% and pregnancy rate per ovulatory cycle as 14.94%. 32 out of 80 women who received 80 mg of tamoxifen conceived, giving a pregnancy rate of 40% and pregnancy rate per cycle as 33.68%. This difference in the pregnancy rate between the two groups was statistically significant. 35 women out of 90 with polycystic ovary syndrome (PCOS) became pregnant with a pregnancy rate of 38.8% and 20 out of 70 women with clomiphene citrate failure conceived, giving a pregnancy rate of 28.5%. CONCLUSIONS: Tamoxifen is a good alternative to clomiphene in women with PCOS and clomiphene-resistant cases. PMID- 22058645 TI - Effect of epilepsy on female fertility and reproductive abnormalities. PMID- 22058646 TI - Finasteride and male fertility. PMID- 22058647 TI - Feature Guided Motion Artifact Reduction with Structure-Awareness in 4D CT Images. AB - In this paper, we propose a novel method to reduce the magnitude of 4D CT artifacts by stitching two images with a data-driven regularization constrain, which helps preserve the local anatomy structures. Our method first computes an interface seam for the stitching in the overlapping region of the first image, which passes through the "smoothest" region, to reduce the structure complexity along the stitching interface. Then, we compute the displacements of the seam by matching the corresponding interface seam in the second image. We use sparse 3D features as the structure cues to guide the seam matching, in which a regularization term is incorporated to keep the structure consistency. The energy function is minimized by solving a multiple-label problem in Markov Random Fields with an anatomical structure preserving regularization term. The displacements are propagated to the rest of second image and the two image are stitched along the interface seams based on the computed displacement field. The method was tested on both simulated data and clinical 4D CT images. The experiments on simulated data demonstrated that the proposed method was able to reduce the landmark distance error on average from 2.9 mm to 1.3 mm, outperforming the registration-based method by about 55%. For clinical 4D CT image data, the image quality was evaluated by three medical experts, and all identified much fewer artifacts from the resulting images by our method than from those by the compared method. PMID- 22058648 TI - Validation of the Marijuana Effect Expectancy Questionnaire-Brief. AB - The purpose of this study was to evaluate a brief version of the Marijuana Effect Expectancy Questionnaire (MEEQ; Schafer & Brown, 1991). The original MEEQ was reduced to 6 items (MEEQ-B). Principal component analysis (PCA) was performed and two factors were identified (positive effects and negative effects) accounting for 52.3% of the variance. Internal consistencies (0.42 to 0.60) were slightly lower than those of the original MEEQ. The negative effect expectancy scale correlated with criterion variables that assess marijuana use (p <= .05). This measure is a helpful tool for clinicians to use when assessing youth expectancies. Replication across different samples of adjudicated youth is recommended. PMID- 22058649 TI - Design and Control of a 1-DOF MRI Compatible Pneumatically Actuated Robot with Long Transmission Lines. AB - This paper presents the design and control of an MRI-compatible 1-DOF needle driver robot and its precise position control using pneumatic actuation with long transmission lines. MRI provides superior image quality compared to other imaging modalities such as CT or ultrasound, but imposes severe limitations on the material and actuator choice (to prevent image distortion) due to its strong magnetic field. We are primarily interested in developing a pneumatically actuated breast biopsy robot with a large force bandwidth and precise targeting capability during radio-frequency ablation (RFA) of breast tumor, and exploring the possibility of using long pneumatic transmission lines from outside the MRI room to the device in the magnet to prevent any image distortion whatsoever. This paper presents a model of the entire pneumatic system. The pneumatic lines are approximated by a first order system with time delay, because its dynamics are governed by the telegraph equation with varying coefficients and boundary conditions, which cannot be solved precisely. The slow response of long pneumatic lines and valve subsystems make position control challenging. This is further compounded by the presence of non-uniform friction in the device. Sliding mode control (SMC) was adopted, where friction was treated as an uncertainty term to drive the system onto the sliding surface. Three different controllers were designed, developed, and evaluated to achieve precise position control of the RFA probe. Experimental results revealed that all SMCs gave satisfactory performance with long transmission lines. We also performed several experiments with a 3-DOF fiber-optic force sensor attached to the needle driver to evaluate the performance of the device in the MRI under continuous imaging. PMID- 22058650 TI - Profiles and majority voting-based ensemble method for protein secondary structure prediction. AB - Machine learning techniques have been widely applied to solve the problem of predicting protein secondary structure from the amino acid sequence. They have gained substantial success in this research area. Many methods have been used including k-Nearest Neighbors (k-NNs), Hidden Markov Models (HMMs), Artificial Neural Networks (ANNs) and Support Vector Machines (SVMs), which have attracted attention recently. Today, the main goal remains to improve the prediction quality of the secondary structure elements. The prediction accuracy has been continuously improved over the years, especially by using hybrid or ensemble methods and incorporating evolutionary information in the form of profiles extracted from alignments of multiple homologous sequences. In this paper, we investigate how best to combine k-NNs, ANNs and Multi-class SVMs (M-SVMs) to improve secondary structure prediction of globular proteins. An ensemble method which combines the outputs of two feed-forward ANNs, k-NN and three M-SVM classifiers has been applied. Ensemble members are combined using two variants of majority voting rule. An heuristic based filter has also been applied to refine the prediction. To investigate how much improvement the general ensemble method can give rather than the individual classifiers that make up the ensemble, we have experimented with the proposed system on the two widely used benchmark datasets RS126 and CB513 using cross-validation tests by including PSI-BLAST position-specific scoring matrix (PSSM) profiles as inputs. The experimental results reveal that the proposed system yields significant performance gains when compared with the best individual classifier. PMID- 22058651 TI - Alternative methods in toxicology: pre-validated and validated methods. AB - The development of alternative methods to animal experimentation has progressed rapidly over the last 20 years. Today, in vitro and in silico methods have an important role in the hazard identification and assessment of toxicology profile of compounds. Advanced alternative methods and their combinations are also used for safety assessment of final products. Several alternative methods, which were scientifically validated and accepted by competent regulatory bodies, can be used for regulatory toxicology purposes, thus reducing or fully replacing living animals in toxicology experimentation. The acceptance of the alternative methods as valuable tools of modern toxicology has been recognized by regulators, including OECD, FDA and EPA.This paper provides a brief overview of the topic "alternative methods in toxicology" and focuses on pre-validated and validated alternative methods and their position in the modern toxicology. PMID- 22058652 TI - Flavonoids in prevention of diseases with respect to modulation of Ca-pump function. AB - Flavonoids, natural phenolic compounds, are known as agents with strong antioxidant properties. In many diseases associated with oxidative/nitrosative stress and aging they provide multiple biological health benefits. Ca(2+)-ATPases belong to the main calcium regulating proteins involved in the balance of calcium homeostasis, which is impaired in oxidative/nitrosative stress and related diseases or aging. The mechanisms of Ca(2+)-ATPases dysfunction are discussed, focusing on cystein oxidation and tyrosine nitration. Flavonoids act not only as antioxidants but are also able to bind directly to Ca(2+)-ATPases, thus changing their conformation, which results in modulation of enzyme activity.Dysfunction of Ca(2+)-ATPases is summarized with respect to their posttranslational and conformational changes in diseases related to oxidative/nitrosative stress and aging. Ca(2+)-ATPases are discussed as a therapeutic tool and the possible role of flavonoids in this process is suggested. PMID- 22058653 TI - Effect of N'-nitrosodimethylamine on red blood cell rheology and proteomic profiles of brain in male albino rats. AB - We investigated the effects of N'-nitrosodimethylamine (NDMA) induced toxicity on red blood cell rheology in male rats and identified bands in proteomic profiles of brain which can be used as novel markers. Polyacrylamide gel electrophoresis (PAGE) profiles exhibited constitutive as well as induced expression of the polypeptides. Remarkably, the molecular weight range of the polypeptides (8-150 kDa) corresponded to that of the family of heat shock proteins. Our results revealed significant changes in blood parameters and showed the presence of acanthocytes, tear drop cells, spicules and cobot rings in the treated categories. Lactate dehydrogenase and esterase zymograms displayed a shift to anaerobic metabolism generating hypoxia-like conditions. This study strongly suggests that NDMA treatment causes acute toxicity leading to cell membrane destruction and alters protein profiles in rats. It is therefore recommended that caution should be exercised in using NDMA to avoid risks, and if at all necessary strategies should be designed to combat such conditions. PMID- 22058654 TI - Differential effects of alprazolam and clonazepam on the immune system and blood vessels of non-stressed and stressed adult male albino rats. AB - Benzodiazepines belongs to one of the most commonly used anxiolytic and anticonvulsant drugs in the world. Full description of toxic effects on different organs is lacking for nearly all the current benzodiazepines. The aim of the current work was to study the immunologic and vascular changes induced by sub chronic administration of alprazolam and clonazepam in non-stressed and stressed adult male albino rats. Forty-two adult male albino rats were divided into 6 groups (I): (Ia) Negative control rats, (Ib): Positive control rats received distilled water, (II): Stressed rats, (III): Non-stressed rats received daily oral dose of clonazepam (0.5 mg/kg), (IV): Stressed rats received daily oral dose of clonazepam (0.5 mg/kg), (V): Non-stressed rats received daily oral dose of alprazolam (0.3 mg/kg). (VI): Stressed rats received daily oral dose of alprazolam (0.3 mg/kg). At the end of the 4th week, total leukocyte count (WBCs) and differential count were determined, anti-sheep RBC antibody (Anti-SRBC) titer and interleukin-2 (IL-2) level were assessed, thymus glands, lymph nodes, spleens and abdominal aortae were submitted to histopathological examination. Alprazolam was found to induce a significant increase in neutrophil count and a significant decrease in lymphocytes, anti-SRBC titer and IL-2 level with severe depletion of the splenic, thymal and nodal lymphocytes, accompanied by congestion and eosinophilic vasculitis of all organs tested in comparison to clonazepam treated rats. Stress enhanced the toxic effects. It was concluded that the immune system and blood vessels can be adversely affected to a greater extent by short-term chronic administration of alprazolam than by clonazepam, and these toxic effects are aggravated by stress. PMID- 22058655 TI - Plasma and whole brain cholinesterase activities in three wild bird species in Mosul, IRAQ: In vitro inhibition by insecticides. AB - Plasma and brain cholinesterase activities were determined in three wild bird species to assess their exposure to organophosphate and carbamate insecticides which are used in agriculture and public health. In the present study, we used an electrometric method for measurement of cholinesterase activities in the plasma and whole brain of three indigenous wild birds commonly found in northern Iraq. The birds used were apparently healthy adults of both sexes (8 birds/species, comprising 3-5 from each sex) of quail (Coturnix coturnix), collard dove (Streptopelia decaocto) and rock dove (Columba livia gaddi), which were captured in Mosul, Iraq. The mean respective cholinesterase activities (Delta pH/30 minutes) in the plasma and whole brain of the birds were as follows: quail (0.96 and 0.29), collard dove (0.97and 0.82) and rock dove (1.44 and 1.42). We examined the potential susceptibility of the plasma or whole brain cholinesterases to inhibition by selected insecticides. The technique of in vitro cholinesterase inhibition for 10 minutes by the organophosphate insecticides dichlorvos, malathion and monocrotophos (0.5 and 1.0 uM) and the carbamate insecticide carbaryl (5 and10 uM) in the enzyme reaction mixtures showed significant inhibition of plasma and whole brain cholinesterase activities to various extents. The data further support and add to the reported cholinesterase activities determined electrometrically in wild birds in northern Iraq. The plasma and whole brain cholinesterases of the birds are highly susceptible to inhibition by organophosphate and carbamate insecticides as determined by the described electrometric method, and the results further suggest the usefulness of the method in biomonitoring wild bird cholinesterases. PMID- 22058656 TI - Oxidative stress biomarkers and acetylcholinesterase activity in human erythrocytes exposed to clomazone (in vitro). AB - The aim of this study was to investigate the effect of clomazone herbicide on oxidative stress biomarkers and acetylcholinesterase activity in human erythrocytes in in vitro conditions. The activity of catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE), as well as the levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were measured in human erythrocytes exposed (in vitro) to clomazone at varying concentrations in the range of 0, 100, 250 and 500 ug/L for 1 h at 37 degrees C.TBARS levels were significantly higher in erythrocytes incubated with clomazone at 100, 250 and 500 ug/L. However, erythrocyte CAT and AChE activities were decreased at all concentrations tested. SOD activity was increased only at 100 ug/L of clomazone. GSH levels did not change with clomazone exposure. These results clearly showed clomazone to induce oxidative stress and AChE inhibition in human erythrocytes (in vitro). We, thus, suggest a possible role of ROS on toxicity mechanism induced by clomazone in humans. PMID- 22058657 TI - Effect of saliva from horse fly Hybomitra bimaculata on kinetic properties of Na,K-ATPase: possible role in regulation of relaxation. AB - The possible involvement of salivary gland extract (SGE) from horse flies in modifying hyperpolarization and relaxation via alterations in functional properties of sarcolemmal Na,K-ATPase in the host tissue was tested in vitro by application of various amounts of SGE from Hybomitra bimaculata.SGE in the amount of 3 ug proteins representing approximately the equivalent of one salivary gland of Hybomitra bimaculata induced a stimulatory effect on Na,K-ATPase at all ATP concentrations applied. This effect resulted from the improved ATP-binding site affinity in the Na,K-ATPase molecule, as implicated by the reduction in K(M). Increasing the amount of SGE to 6.5 ug resulted in inhibition of the enzyme, which was characterized by reduction in V(max) and also K(M). This suggests that in the presence of relatively high Hybomitra bimaculata SGE concentration some SGE components affect Na,K-ATPase, when ATP is already bound to the enzyme.Our results indicate that SGE from the horse fly Hybomitra bimaculata contain at least two different biologically active compounds modifying the acute recovery and maintenance of excitability during contractile activity in the host tissue by affecting Na,K-ATPase with opposite effects, depending on the ratio of SGE proteins to proteins of the host tissue. PMID- 22058658 TI - Effect of methyl methanesulfonate on hsp70 expression and tissue damage in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ) Bg. AB - Methyl methanesulfonate (MMS) is an anti-carcinogenic drug and its toxicity has been reported in various experimental models. The hsp70s are a family of ubiquitously expressed heat shock proteins. In the recent years, hsp70 has been considered to be one of the candidate genes for predicting cytotoxicity against environmental chemicals. Nowadays emphasis is given to the use of alternatives to mammals in testing, research and education. The European Centre for the Validation of Alternative Methods (EVCAM) has recommended the use of Drosophila as an alternative model for scientific studies. Almost all living organisms possess proteins with a similar structure to that of hsp70s. In the present study, the toxicity of MMS was evaluated by quantifying hsp70 expression and tissue damage in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ) Bg(9), at different doses and hours of exposure. We studied the effect of 0.25, 0.50, 0.75 and 1.0 ul/ml of MMS at 2, 4, 24 and 48 hours of exposure on hsp70 expression by using the soluble O-nitrophenyl-beta-D galactopyranoside (ONPG) assay and on establishing the tissue damage by the Trypan blue exclusion assay in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ) Bg(9). A dose-dependent increase in the expression of hsp70 was observed at 0.25, 0.50, and 0.75 ul/ml of MMS compared to the control. At the highest dose, i.e. 1.0 ul/ml of MMS, the activity of hsp70 was decreased due to tissue damage. PMID- 22058659 TI - The Subjective Experience of Social Class and Upward Mobility Among African American Men in Graduate School. AB - We used Consensual Qualitative Research Methodology to analyze responses from 14 African American men (Mdn(Age) = 25 years-old) in graduate school at a predominantly-White university in the Midwestern region of the United Sates regarding how they acquired awareness of their social-class status; how social class was related to their sense of masculinity; how social class was related to race and skin tone; and the role that education and a romantic partner could play in upward mobility. School peers were the main source for their early awareness of social class. Many believed that discrimination maintains social class stratification that disadvantages racial minorities and that one's race will always trump any personal characteristics-including having light-complected skin and an advanced degree. Finally many overcame several obstacles during their educational career, and most believed that a romantic relationship with a woman from a privileged background could facilitate upward mobility. Psychological scientists and practitioners are encouraged to consider the role that social class plays when examining men's well-being. PMID- 22058660 TI - Mussel-Inspired Adhesives and Coatings. AB - Mussels attach to solid surfaces in the sea. Their adhesion must be rapid, strong, and tough, or else they will be dislodged and dashed to pieces by the next incoming wave. Given the dearth of synthetic adhesives for wet polar surfaces, much effort has been directed to characterizing and mimicking essential features of the adhesive chemistry practiced by mussels. Studies of these organisms have uncovered important adaptive strategies that help to circumvent the high dielectric and solvation properties of water that typically frustrate adhesion. In a chemical vein, the adhesive proteins of mussels are heavily decorated with Dopa, a catecholic functionality. Various synthetic polymers have been functionalized with catechols to provide diverse adhesive, sealant, coating, and anchoring properties, particularly for critical biomedical applications. PMID- 22058661 TI - Parameterization of a B3LYP specific correction for non-covalent interactions and basis set superposition error on a gigantic dataset of CCSD(T) quality non covalent interaction energies. AB - A vast number of non-covalent interaction energies at the counterpoise corrected CCSD(T) level have been collected from the literature to build a diverse new dataset. The whole dataset, which consists of 2027 CCSD(T) energies, includes most of the published data at this level. A large subset of the data was then used to train a novel, B3LYP specific, empirical correction scheme for non covalent interactions and basis set superposition error (abbreviated as B3LYP MM). Results obtained with our new correction scheme were directly compared to benchmark results obtained with B3LYP-D3(1) and M06-2X(2) (two popular density functions designed specifically to accurately model non-covalent interactions). For non-covalent complexes dominated by dispersion or dipole-dipole interactions all three tested methods give accurate results with the medium size aug-cc-pVDZ(3 6) basis set with MUE's of 0.27 (B3LYP-MM), 0.32 (B3LYP-D3) and 0.47 kcal/mol (M06-2X) (with explicit counterpoise corrections). These results validate both B3LYP-D3 and M06-2X for interactions of this type using a much larger data set than was presented in prior work. However, our new dispersion correction scheme shows some clear advantages for dispersion and dipole-dipole dominated complexes with the small LACVP* basis set, which is very popular in use due to its low associated computational cost: The MUE for B3LYP-MM with the LACVP* basis set for this subset of complexes (without explicit counterpoise corrections) is only 0.28 kcal/mol, compared to 0.65 kcal/mol for M06-2X or 1.16 kcal/mol for B3LYP-D3. Additionally, our new correction scheme also shows major improvements in accuracy for hydrogen-bonded systems and for systems involving ionic interactions, for example cation-pi interactions. Compared to B3LYP-D3 and M06-2X, we also find that our new B3LYP-MM correction scheme gives results of higher or equal accuracy for a large dataset of conformer energies of di- and tripeptides, sugars, and cysteine. PMID- 22058662 TI - Are There Racial Ethnic Differences in Indigent, Inner-City Clients With Dual Diagnosis? AB - OBJECTIVE: An exploratory, cross-sectional study examined personal, clinical, and treatment characteristics among non-Hispanic Caucasian, non-Hispanic African American, and Hispanic indigent, inner-city clients with co-occurring disorders. METHODS: Men and women, 20-50 years old who met DSM-IV criteria for concurrent mood and substance use disorders were eligible. Inpatients, persons in detoxification programs, or incarcerated inmates were excluded. Assessments covered sociodemographic characteristics, clinical diagnoses, substance use, psychosocial variables, health care utilization and treatment history. RESULTS: Two hundred volunteers were screened, and 145 were eligible to enroll. Racial ethnic group differences in the distribution of mood and substance use disorders and medical diseases were evident. Receiving psychiatric treatment and psychiatric medications significantly differed among racial ethnic groups with Caucasians more likely to receive these services than African Americans or Hispanics. African Americans and Hispanics were also more likely than Caucasians to test positive for their drug of choice and for other drugs as well. Serious medical illnesses were evident in about half of the sample, and the distributions of these illnesses significantly differed among racial ethnic groups. There were no significant differences in hospitalization or emergency room visits among racial ethnic groups. CONCLUSIONS: Indigent, inner-city clients have multiple psychiatric and medical problems that warrant continuity of care. However, few doctor's visits for medical illnesses, lack of psychotropic medications, staggering unemployment, and homelessness were common in our sample. These results present healthcare and social service professionals with potentially serious treatment challenges. Better recognition and understanding of racial ethnic needs in those with co-occurring disorders are needed. PMID- 22058663 TI - Black men have lower rates than white men of biochemical failure with primary androgen-deprivation therapy. AB - INTRODUCTION: Black men have a higher incidence of advanced stage at diagnosis and mortality from prostate cancer than do men in other racial groups. Given that androgen-deprivation therapy (ADT) is one of the mainstays of treatment for advanced prostate cancer, we investigated the development of biochemical failure, or recurrence of elevated prostate-specific antigen (PSA) levels, among different races in men receiving ADT. METHODS: Patients with prostate cancer who received ADT in the Kaiser Permanente Southern California Cancer Registry between January 2003 and December 2006 were eligible for inclusion in our study. Patients who had prior treatment for their cancer with surgery or radiation were excluded. Treatment failure was defined as an increase in PSA of >2 ng/mL from PSA nadir, with no subsequent decrease in PSA. We compared the biochemical failure rate in white patients to those in black, Hispanic, and Asian/other patients. The Cox proportional hazards regression model was used to estimate hazards ratios. RESULTS: Our study population consisted of 681 patients: 416 (61%) were white; 107 (16%) were black; 107 (16%) were Hispanic; and 51 (7%) were Asian or another race. After we controlled for all demographic variables and for variables related to prostate cancer, blacks were the only group with a lower risk of treatment failure compared with whites. The hazard ratios for treatment failure were as follows: black versus white, 0.66 (p = 0.03); Hispanic versus white, 1.00 (p = 0.8); Asian/other race versus white, 1.5 (p = 0.1). In this multivariate analysis, pretreatment PSA level and cancer stage were the only other variables associated with a higher risk of treatment failure. CONCLUSION: Among patients receiving ADT as primary monotherapy for prostate cancer, blacks may have a lower rate of biochemical failure compared with whites. Although the etiology of this finding is unclear, it suggests the possibility that prostate cancer in black men may be more androgen sensitive than it is in white men. PMID- 22058664 TI - Building teams in primary care: what do nonlicensed allied health workers want? AB - INTRODUCTION: Nonlicensed allied health workers are becoming increasingly important in collaborative team care, yet we know little about their experiences while filling these roles. To explore their perceptions of working as health coaches in a chronic-disease collaborative team, the teamlet model, we conducted a qualitative study to understand the nature and dynamics of this emerging role. METHODS: During semistructured interviews, 11 health coaches reflected on their yearlong experience in the teamlet model at an urban underserved primary care clinic. Investigators conducted a thematic analysis of transcriptions of the interviews using a grounded theory process. RESULTS: Four themes emerged: 1) health-coach roles and responsibilities included acting as a patient liaison between visits, providing patient education and cultural brokering during medical visits, and helping patients navigate the health care system; 2) communication and relationships in the teamlet model of care were defined by a triad of the patient, health coach, and resident physician; 3) interest in the teamlet model was influenced by allied health workers' prior education and health care roles; and 4) factors influencing the effectiveness of the model were related to clinical and administrative time pressures and competing demands of other work responsibilities. CONCLUSION: Nonlicensed allied health workers participating in collaborative teams have an important role in liaising between patients and their primary care physicians, advocating for patients through cultural brokering, and helping patients navigate the health care system. To maximize their job satisfaction, their selection should involve strong consideration of motivation to participate in these expanded roles, and protected time must be provided for them to carry out their responsibilities and optimize their effectiveness. PMID- 22058665 TI - Coffee, caffeine, and risk of hospitalization for arrhythmias. AB - CONTEXT: Population study data about relations of coffee drinking to arrhythmia are sparse. OBJECTIVE: To study relations of coffee drinking to risk of cardiac arrhythmia in 130,054 persons with previous data about coffee habits.Design and Outcome Measure: We used Cox proportional hazards models with 8 covariates to study coffee-related risk in 3137 persons hospitalized for cardiac arrhythmia. We conducted a similar analysis of total caffeine-related risk in a subgroup with data about other caffeine intake (11,679 study participants; 198 hospitalized). RESULTS: With non-coffee-drinkers as the referent, the adjusted hazard ratio (HR) for any arrhythmia at the level of <1 cup of coffee per day was 1.0 (95% confidence interval [CI] = 0.9-1.1; p = 0.7); for 1-3 cups/day, it was 0.9 (CI, 0.8-1.0; p = 0.2), and for >=4 cups/day, it was 0.8 (CI, 0.7-0.9; p = 0.002). With coffee intake as a continuous variable, the HR per cup per day was 0.97 (CI, 0.95-0.99; p = 0.001). RESULTS were similar for several strata, including persons with history or symptoms of possible cardiore-spiratory disease and those without such history or symptoms. Coffee had similar relations to atrial fibrillation (48% of participants with arrhythmia) and most other specific arrhythmia diagnoses. Controlled for number of cups of coffee per day, total caffeine intake was inversely related to risk (HR highest quartile vs lowest = 0.6; p = 0.03). CONCLUSION: The inverse relations of coffee and caffeine intake to hospitalization for arrhythmias make it unlikely that moderate caffeine intake increases arrhythmia risk. PMID- 22058666 TI - Optimizing Treatment of Intra-amniotic Infection and Early-Onset Postpartum Endometritis: Advantages of Single-Agent Therapy. AB - INTRODUCTION: Intra-amniotic infection (IAI) and early-onset postpartum endometritis (PPE) require prompt antibiotic treatment and are generally treated by either of two regimens. A complicated multi-agent regimen is most commonly used, despite a lack of clear evidence that it produces better outcomes than a simpler single-agent regimen. OBJECTIVE: We compared treatment outcomes between a multi-agent regimen of ampicillin, gentamicin, and clindamycin versus a single agent regimen of ampicillin/sulbactam for IAI and early-onset PPE. METHODS: We conducted an observational retrospective cohort study by collecting data from the records of all patients at Denver Health Medical Center treated for IAI or PPE during two 6-month periods: a baseline period during which a regimen of ampicillin, gentamicin, and clindamycin was used and a subsequent period when ampicillin/sulbactam was used. Primary outcomes were prolonged antibiotic treatment and readmission for endometritis or wound cellulitis. RESULTS: Of potential study participants, 323 women met inclusion criteria; 179 were treated with the multi-agent regimen and 144 were treated with the single-agent regimen. The groups were statistically similar for demographic and intrapartum characteristics, except for a lower rate of premature rupture of membranes in the single-agent treatment group. Twelve patients required prolonged treatment, and 2 were readmitted; these subgroups were combined for statistical analyses. The primary outcomes were significantly associated with cesarean delivery and blood loss >500 mL for vaginal deliveries and >1000 mL for cesarean deliveries; however, there was no significant difference in the incidence of the primary outcomes between the 2 treatment groups when adjusted for these variables. Treatment with ampicillin/sulbactam resulted in fewer antibiotic doses administered to patients with an uncomplicated treatment course. CONCLUSION: Ampicillin/sulbactam treatment of IAI and early-onset PPE reduces the number of antibiotic doses administered and results in patient outcomes similar to those for the standard multi-agent therapy of ampicillin, gentamicin, and clindamycin. PMID- 22058667 TI - Virtual visitation in the neonatal intensive care: experience with the use of internet and telemedicine in a tertiary neonatal unit. AB - INTRODUCTION: Globally about 8% to 10% of newborns require neonatal intensive care (NICU) care. Families face emotional and financial difficulties when their sick newborns are hospitalized for prolonged periods in a NICU. METHODS: We conducted a study to assess the feasibility and acceptance of an Internet-based telemedicine program in an intensive care setting and to evaluate its impact on newborns' length of stay (LOS) in hospitals. We identified eligible newborns and obtained their parents' written consent before installing a Web camera by the babies' beds. Using child-specific, confidential passwords, families viewed real time video images of their newborns through a secure portal via an Internet browser or 3G (third-generation) cell phone. Parents of study subjects completed a survey that detailed the performance of the system. Frequency of parental visits and LOS of babies were tracked and compared with the same data for similar high-risk newborns matched for gestation and birth weight. RESULTS: Parents responded favorably to the stability of the system and clarity of the image. Eighty percent requested a larger image frame. Frequencies of hospital visits made by parents of newborns in the study group and of those made by parents in the control group were not statistically different. LOS and postmenstrual age on discharge of study infants were not statistically different compared with infants in the control group. CONCLUSION: Virtual visitation is well accepted by families with sick newborns requiring prolonged hospitalization. Inclusion of information technology to optimize NICU visitation resulted in no significant decrease in duration of hospitalization; however, its role in improving post-discharge transition care must be evaluated further. PMID- 22058668 TI - Building a System of Care: Integration across the Heart Failure Care Continuum. AB - CONTEXT: MaineHealth provides chronic disease programs using The Planned Care Model as its framework. Over time, programs have evolved from working in silos to integrating across care arenas and organizations, resulting in a coordinated, reliable, and standardized system of care. Nowhere is this more apparent than in the system's heart failure (HF) programs. For years, disparate HF services existed across MaineHealth. The system lacked a comprehensive, integrated approach to support patients and families transitioning across multiple care environments. OBJECTIVE: Develop and implement a systemwide set of interventions to facilitate communication between clinicians in different care environments, consistent approaches to patient and clinician education, and improvement of clinical performance. DESIGN: An interdisciplinary Joint Heart Failure Workgroup was convened. Relationships were developed between "champions" from diverse care settings and professions. Champions assisted MaineHealth in leading the workgroup, creating a comprehensive set of strategies that better linked HF activities and care settings across the health system. MAIN OUTCOME MEASURES: Readmission rates, core measures, use of home telemonitoring, patient confidence in self management. RESULTS: The impact of collaboration and integration has been substantial, resulting in better communication, coordination, reliability, and standardization of HF care. CONCLUSION: Through the use of a comprehensive set of improvement strategies, MaineHealth has been successful in overcoming many cultural and structural barriers to increase communication and integration across programs and care settings, and leveraging resources to improve outcomes in patients with HF. PMID- 22058669 TI - Qualitative Assessment of the Impact of Implementing Reiki Training in a Supported Residence for People Older Than 50 Years with HIV/AIDS. AB - INTRODUCTION: Reiki is a Japanese form of energy healing that has become popular in the US. Reiki training involves three stages-levels I, II, and III-to a master practitioner level and requires both giving and receiving Reiki. We set out to implement a program to train clients of a supported residence in Brooklyn, NY. They were all older than age 50 years and had HIV/AIDS and substance-abuse and/or mental-health disorders. METHODS: A qualitative, narrative-inquiry study was conducted. The Reiki master kept a journal of her 3 years of providing 90 minutes of Reiki treatment and/or training once weekly at the residence. Forty-five of 50 potential participants attended these sessions with various frequencies. Stories were collected from 35 participants regarding their experience of Reiki training. We posited success as continued involvement in the program. RESULTS: All 35 participants reported receiving benefit from participation in Reiki. Participants first took part in training because of the offered subway tokens; however, 40 continued their involvement despite a lack of compensation. When asked why they continued, participants reported life-changing experiences, including a greater ability to cope with addictions, a greater ability to manage counseling, healing of wounds, improvement of T-cell counts, and improved skills of daily living. CONCLUSION: Reiki training can be successfully implemented in a supported housing facility with people with HIV/AIDS and comorbid disorders. Some people in our study population reported areas of improvement and life-changing experiences. Our study did not establish the efficacy of Reiki, but our findings support the effect of the entire gestalt of implementing a program related to spirituality and healing and supports the goal of implementing a larger randomized, controlled trial in this setting to establish the efficacy of Reiki. PMID- 22058670 TI - Hospital Medicine's Evolution: Literature Search and Interview Study with Practices. AB - INTRODUCTION: Hospital medicine is a young specialty that is still evolving. In its early years, research focused on clinical outcomes, efficiency, and cost effectiveness. As the specialty matures, increasing attention is being given to the patient and hospitalist experience with the hospitalist model of care. METHODS: In 2008, we conducted a literature search to identify patients' and hospitalists' satisfaction concerns and potential strategies for their resolution. We used our findings to develop a semistructured interview guide as a basis for a wide-ranging discussion with Kaiser Permanente (KP) hospitalists and physician leaders and KP and non-KP subject-matter experts on their priorities, concerns, and successful practices. RESULTS: Respondents identified sustainability and communications in coordinating care as their high-priority concerns with sustainability as the top priority. Within these broad concerns, they identified contributing factors and their interrelationships. Factors influencing sustainability of the hospitalist model include hospitalist scheduling, workload, comanagement responsibilities, and recruitment and retention. Regarding communications in coordinating care, respondents viewed themselves as being in the center of a web involving communication with patients, physicians in other services, nurses, and other hospitalists. CONCLUSION: Promising approaches have been developed to address sustainability concerns and for communicating with patients, physicians in other services, nurses, and other hospitalists. However, getting reliable feedback on patient satisfaction surveys for individual hospitalists is a continuing challenge. Despite the use of brochures and business cards to introduce themselves to patients and explain their role, there are difficulties in establishing a hospitalist-patient bond. PMID- 22058671 TI - The role of minimally invasive surgery and outcomes in colorectal cancer. AB - For some time now, there has been significant interest in understanding and defining the role of minimally invasive surgery in colorectal cancer. Laparoscopic surgery has been shown to have similar or better outcomes compared with open surgery. Recently, prospective randomized trials have demonstrated oncologic outcomes of laparoscopic colon surgery equivalent to those for open surgery. However, the technical challenges of performing laparoscopic resection of rectal cancers and the uncertainty of the oncologic quality of the surgical resection have hindered the growth of minimally invasive rectal surgery. Robotic rectal surgery has recently emerged as an attractive alternative to laparoscopic surgery because it allows for superior visualization within a narrow pelvic field and more precise dissection. Studies of robotic rectal resection have suggested similar or potentially improved short-term oncologic outcomes when compared with laparoscopic rectal resection. Ongoing randomized studies will provide additional insight into the role of laparoscopic and minimally invasive robotic surgery for rectal cancer. PMID- 22058672 TI - Improving diagnostic reasoning to improve patient safety. AB - Both clinicians and patients rely on an accurate diagnostic process to identify the correct illness and craft a treatment plan. Achieving improved diagnostic accuracy also fulfills organizational fiscal, safety, and legal objectives. It is frequently assumed that clinical experience and knowledge are sufficient to improve a clinician's diagnostic ability, but studies from fields where decision making and judgment are optimized suggest that additional effort beyond daily work is required for excellence. This article reviews the cognitive psychology of diagnostic reasoning and proposes steps that clinicians and health care systems can take to improve diagnostic accuracy. PMID- 22058673 TI - The treatment of black widow spider envenomation with antivenin latrodectus mactans: a case series. AB - Black widow spiders (Latrodectus mactans) are found throughout the US. Though bites are relatively uncommon, they pose a significant health problem with over 2500 reported to American poison control centers annually. Black widow spider bites cause a characteristic envenomation syndrome consisting of severe pain, muscle cramping, abdominal pain, and back pain. The significant pain associated with envenomation is often refractory to traditional analgesics. Antivenom (Antivenin Latrodectus mactans) is available and effective, but is often withheld because of a fear of acute hypersensitivity reactions. We report four cases of symptomatic black widow spider envenomation. One of the reported cases was managed without antivenom, and, in contrast, three were treated successfully with Antivenin Latrodectus mactans. We believe that these cases demonstrate safe and effective use of black widow antivenom. This article presents the rationale for use of antivenom in these cases, and a nonsystematic review of the pertinent literature. PMID- 22058674 TI - Acute Myocardial Infarction due to Coronary Artery Embolism in a Patient with a Tissue Aortic Valve Replacement. AB - Acute occlusive embolism to the coronary arteries resulting in acute myocardial infarction (AMI) is an uncommon occurrence. Although cases of patients with mechanical prosthetic heart valves resulting in this phenomenon have been reported in the setting of inadequate anticoagulation, reported cases resulting years after tissue aortic valve replacement (AVR) are rare. We report the case of a 50-year-old man who underwent a tissue AVR four years earlier and presented to the Emergency Department (ED) with an ST-segment elevation myocardial infarction. ED door-to-balloon time was delayed (at 115 minutes) because of pre-existing left bundle branch block on electrocardiogram. Emergent coronary angiography demonstrated complete occlusion of the left anterior descending coronary artery by a coronary embolus. The patient was successfully treated with percutaneous transluminal coronary angioplasty and aspiration thrombectomy, and subsequently underwent a transesophageal echocardiogram demonstrating thrombus on the tissue aortic valve prosthesis. This case demonstrates that coronary embolism resulting in AMI, while rare, can occur in patients years after tissue AVR surgery. PMID- 22058675 TI - Climate Change: It's Not About the Weather-Continuing Medical Education and Maintenance of Certification and Licensure. PMID- 22058676 TI - When Disaster Strikes, Humanity Becomes our Patient. PMID- 22058677 TI - Innovation in Our Nation's Public Hospitals: Three-Year Follow-Up Interview with Five CEOs and Medical Directors-Part 2. PMID- 22058678 TI - Notice of retraction. PMID- 22058679 TI - Retraction of articles. AB - This article reports the retraction of five articles published in Acta Crystallographica Section E between 2004 and 2011. PMID- 22058680 TI - A new langbeinite-type phosphate: K(2)AlSn(PO(4))(3). AB - Single crystals of the title compound, dipotassium aluminium tin(IV) tris [phosphate(V)], K(2)AlSn(PO(4))(3), were synthesized by a high temperature reaction in a platinum crucible. In the structure, the Al(III) and Sn(IV) atoms occupy the same site on a threefold rotation axis with occupational disorder in a 1:1 ratio. In the three-dimensional structure, Al/SnO(6) octa-hedra and PO(4) tetra-hedra are inter-connected via their vertices, yielding a [Al/SnP(3)O(12)](n) framework. The K atoms (site symmetry 3) reside in the large cavities delimited by the [Al/SnP(3)O(12)](n) framework, and are surrounded by 12 O atoms. PMID- 22058681 TI - Potassium deca-borate monohydrate. AB - In the crystal structure of the title compound, K(2)[B(10)O(14)(OH)(4)].H(2)O, the polyborate [B(10)O(14)(OH)(4)](2-) anions are linked together through their common O atoms, forming a helical chain-like structure. Adjacent chains are further connected into a three-dimensional structure by O-H?O hydrogen bonds. The water mol-ecules and potassium cations are located between these chains. Further O-H?O hydrogen bonds occur between the anions and the water mol-ecules. PMID- 22058682 TI - Thorium divanadate dihydrate, Th(V(2)O(7))(H(2)O)(2). AB - The title compound, Th(V(2)O(7))(H(2)O)(2), was synthesized by a hydro-thermal reaction. The crystal structure consists of ThO(7)(OH(2))(2) tricapped trigonal prisms that share edges, forming [ThO(5)(OH(2))(2)](n) chains along [010]. The edge-sharing ThO(7)(OH(2))(2) polyhedra share one edge and five vertices with the V(2)O(7) divanadate anions having a nearly ecliptic conformation parallel to [001]. This results in an open framework with the water mol-ecules located in channels. O-H?O hydrogen bonding between water molecules and framework O atoms is observed. Bond-valence-sum calculations are in good agreement with the chemical formula of the title compound. PMID- 22058683 TI - A second polymorph of chlorido(hydroxy-diphenyl-phosphane)gold(I). AB - The title complex, [AuCl{(C(6)H(5))(2)P(OH)-kappaP}] or [AuCl(C(12)H(11)OP)], contains two independent mol-ecules in the asymmetric unit and is a polymorph of a previously reported structure [Hollatz et al. (1999 ?) J. Chem. Soc. Dalton Trans. pp. 111-114]. The crystal structure exhibits inter-molecular Au?Au inter actions with alternate distances of 3.0112 (3) A and 3.0375 (2) A. The Cl-Au-P bond angle varies between different mol-ecular units, depending on the degree of influence of the intra-molecular the O-H?Cl hydrogen bond; the angle thus varies between negligible distortion from linearity at 179.23 (3) degrees and more significant distortion at 170.39 (4) degrees , which differs from the previously reported polymorph in which both these angles are approximately 170 degrees . The Au-Cl [2.3366 (9) and 2.3131 (10)A] and Au-P [2.2304 (10) and 2.2254 (10) A] bond lengths vary slightly between the two independent mol-ecules but overall, the bond lengths are in good agreement with those in the previously reported polymorph. PMID- 22058684 TI - catena-Poly[[triaqua-nickel(II)]-MU-5-carb-oxy-benzene-1,3-dicarboxyl-ato kappaO:O]. AB - In the title compound, [Ni(C(9)H(4)O(6))(H(2)O)(3)](n), the Ni(II) ion has a distorted NiO(5) square-pyramidal geometry, the maximum deviation from the least squares plane formed by the basal atoms being 0.9351 (13) A. The basal plane is formed by two O atoms from carboxyl-ate residues of the 5-carb-oxy-benzene-1,3 dicarboxyl-ate ligand and by two O atoms from water mol-ecules. The O atom of the third water mol-ecule is axially positioned, 1.7890 (19) A perpendicular to the basal plane. The 5-carb-oxy-benzene-1,3-dicarboxyl-ate ligand bridges the metal atoms, forming a polymeric chain along the b axis. O-H?O hydrogen bonds between the water mol-ecules and carboxyl-ate groups stabilize the crystal structure. PMID- 22058685 TI - Diaqua-iodido(2,3,5,6-tetra-2-pyridyl-pyrazine-kappaN,N,N)manganese(II) iodide monohydrate. AB - The asymmetric unit of the title compound, [MnI(C(24)H(16)N(6))(H(2)O)(2)]I.H(2)O, consists of a cationic Mn(II) complex, an I(-) anion and a solvent water mol-ecule. In the complex, the Mn(II) ion is six coordinated in a considerably distorted octa-hedral environment defined by three N atoms of the tridentate 2,3,5,6-tetra-2-pyridyl-pyrazine (tppz) ligand, one I( ) anion and two O atoms of two water ligands. The dihedral angles between the pyridyl rings [maximum deviation = 0.034 (6) A] and their carrier pyrazine ring [maximum deviation = 0.020 (6) A] are 26.5 (2) and 27.0 (2) degrees for the coordinated pyridyl rings, and 51.3 (3) and 43.2 (2) degrees for the uncoordinated pyridyl rings. Inter-molecular O-H?O, O-H?N and O-H?I hydrogen bonds stabilize the crystal structure. PMID- 22058686 TI - Bis(MU-2-phenyl-acetato-kappaO:O)bis-[(2,2'-bipyridyl-kappaN,N')(2-phenyl-acetato kappaO)copper(II)] dihydrate. AB - The mol-ecule of the binuclear title complex, [Cu(2)(C(8)H(7)O(2))(4)(C(10)H(8)N(2))(2)].2H(2)O, is located on an inversion centre. The Cu atoms are bridged by two O atoms of the monodentate phenyl-acetate groups [Cu-O = 1.9808 (14) and 2.3668 (14) A]. The longer of the two bridging Cu O bonds takes the apical position of the distorted square-pyramidal environment of the Cu atom, which is completed by two N atoms of the chelate 2,2'-bipyridine ligand [Cu-N = 2.0107 (17) and 2.0234 (16) A]. The mol-ecules are assembled into stacks along [100] through pi-pi inter-actions with inter-planar distances of 3.630 (4) and 3.407 (3) A; the resulting stacks are further connected into a three-dimensional supra-molecular architecture by O-H?O and C-H?O hydrogen bonding inter-actions. PMID- 22058687 TI - Bis(acrylonitrile-kappaN)dichlorido(eta-cyclo-octa-1,5-diene)ruthenium(II). AB - In the title complex, [RuCl(2)(C(8)H(12))(C(3)H(3)N)(2)], the metal ion is coordinated to centers of each of the double bonds of the cyclo-octa-1,5-diene ligand, to two chloride ions (in cis positions) and to two N-atom donors from two acrylonitrile mol-ecules that complete the coordination sphere for the neutral complex. The coordination about the Ru(II) atom can thus be considered octa hedral with slight trigonal distortion. The three C atoms of one of the acrylonitrile ligands are disordered over two sets of sites in a 0.581 (13):0.419 (13) ratio. PMID- 22058688 TI - trans-Bis[4-amino-3,5-bis-(2-pyrid-yl)-4H-1,2,4-triazole-kappaN]diaqua-cobalt(II) bis-(3-carb-oxy-5-nitro-benzoate). AB - The title complex, [Co(C(12)H(10)N(6))(2)(H(2)O)(2)](C(8)H(4)NO(6))(2), is composed of a mononuclear cobalt(II) cation and two 3-carb-oxy-5-nitro-benzoate anions for charge balance. In the cation, the Co(II) atom is six-coordinated in a distorted octa-hedral geometry. It bonds to two O atoms of two water mol-ecules, and two pairs of N atoms from two 4-amino-3,5-bis-(2-pyrid-yl)-4H-1,2,4-triazole mol-ecules, which behave as bidentate chelating ligands. There are intra molecular N-H?N hydrogen bonds in the cation. In the crystal, there are a number of inter-molecular N-H?O and O-H?O hydrogen bonds, as well as inter-molecular pi pi stacking inter-actions [centroid-centroid distances = 3.657 (2) and 3.847 (2) A], that link the mol-ecules into two-dimensional networks lying parallel to the ab plane. The presence of C-H?O inter-actions leads to the formation of a three dimensional network. PMID- 22058689 TI - Poly[[MU(7)-l-cysteato(2-)]disodium]. AB - The title compound {systematic name: poly[[MU(7)-(2R)-2-amino-3-sulfonato-propano ato]disodium]}, [Na(2)(C(3)H(5)NO(5)S)](n), was obtained through solvent-thermal reaction of l-cysteic acid and aqueous sodium hydroxide. The monomer consists of two Na(+) cations that are coordinated to the deprotonated amino acid. The latter acts as donor utilizing all available coordination sites, viz. the amino, the carboxyl-ate and the sulfonate residues, so producing a monomeric framework in which the two coordinated Na(+) ions have different coordination spheres and geometries. One of the Na(+) ions has an O(5) coordination sphere with a typical geometric arrangement, inter-mediate between trigonal-bipyramidal and square pyramidal; all the O atoms from the amino acid (three from the sulfonate and two from the caboxylate residues) act as donors. The second Na(+) ion is tetracoordinated within an NO(3) coordination sphere. The Na(+) ion binds to the amino N atom, to one of the O atom of the carb-oxy-lic residue and to two O atoms of the sulfonate group in a distorted tetra-hedral arrangement. As the sulfonate O atoms bind to both Na(+) ions, a three-dimensional polymeric framework is obtained. PMID- 22058690 TI - cis-Dichloridobis{[4-(dimethyl-amino)-phen-yl]diphenyl-phosphane kappaP}platinum(II) ethyl acetate monosolvate. AB - The title compound, [PtCl(2)(C(20)H(20)P)(2)].C(4)H(8)O(2), crystallizes with the Pt atom in a distorted cis-square-planar geometry. The Pt-P bond lengths are 2.2490 (19) and 2.253 (2) A, and the Pt-Cl bond lengths are 2.344 (2) and 2.3475 (18) A. Some weak C-H?Cl and C-H?O inter-actions involving the solvate mol-ecule were observed. PMID- 22058691 TI - Tetra-kis(MU(2)-2-phen-oxy-propionato)-kappaO,O':O';kappaO:O,O';kappaO:O'-bis [(1,10-phenanthroline-kappaN,N')(2-phen-oxy-propionato-kappaO,O')lanthanum(III)]. AB - In the centrosymmetric binuclear title complex, [La(2)(C(9)H(9)O(3))(6)(C(12)H(8)N(2))(2)], the two La(III) ions are linked by four 2-phen-oxy-propionate (L) groups in bi- and tridentate bridging modes. Each La(III) ion is nine-coordinated by one 1,10-phenanthroline mol-ecule, one bidentate chelating carboxyl-ate group and four bridging carboxyl-ate groups in a distorted LaN(2)O(7) monocapped square-anti-prismatic geometry. PMID- 22058692 TI - Bis(MU(2)-2-phen-oxy-propionato-kappaO:O')bis-[(1,10-phenanthroline-kappaN,N')bis (2-phen-oxy-propionato-kappaO,O')ytterbium(III)]. AB - In the centrosymmetric binuclear title complex, [Yb(2)(C(9)H(9)O(3))(6)(C(12)H(8)N(2))(2)], the two Yb(III) ions are linked by two 2-phen-oxy-propionate (L) groups in a bidentate bridging mode. Each Yb(III) ion is eight-coordinated by two O atoms from two bridging L ligands, four O atoms from two chelating L groups and two N atoms from one chelating phen mol-ecule in a distorted YbN(2)O(6) dodeca-hedral geometry. PMID- 22058693 TI - Tri-MU-chlorido-bis-[(eta-hexa-methyl-benzene)-ruthenium(II)] tetra-chlorido ferrate(III). AB - The mol-ecular geometry of the complex cation in the title structure, [(MU Cl)(3){Ru(II)(eta(6)-C(6)Me(6))}(2)][Fe(III)Cl(4)], compares very well with that reported earlier for the corresponding PF(6) (-) salt [Pandey et al. (1999 ?). J. Organomet. Chem.592, 278-282]. The [FeCl(4)](-) counter ion has a rather regular tetra-hedral geometry with Fe-Cl distances and Cl-Fe-Cl angles in the range 2.1891 (7)-2.2018 (8) A and 107.10 (3)-110.56 (3) degrees , respectively. There are no significant inter-molecular inter-actions in the crystal except for some weak C-H?Cl contacts, which in turn indicates that the crystal packing is determined predominantly by electrostatic inter-actions between the ionic constituents. PMID- 22058694 TI - Bis(MU-3-chloro-benzene-1,2-dicarboxyl-ato-kappaO:O)bis-[diaqua-(5,5'-dimethyl 2,2'-bipyridine-kappaN,N')copper(II)]. AB - In the centrosymmetric binuclear title compound, [Cu(2)(C(8)H(3)ClO(4))(2)(C(12)H(12)N(2))(2)(H(2)O)(4)], the Cu(II) ion is six coordinated by two N atoms from a 5,5'-dimethyl-2,2'-bipyridine ligand, two bridging O atoms from two 3-chloro-benzene-1,2-dicarboxyl-ate ligands and two water mol-ecules in a distorted octa-hedral geometry. The binuclear complex mol ecules are linked together by inter-molecular O-H?O hydrogen bonds into a layer parallel to (100). The layers are connected by C-H?Cl hydrogen bonds. Intra molecular O-H?O hydrogen bonds and pi-pi inter-actions [centroid-centroid distance = 3.5958 (16) A] are also present. PMID- 22058695 TI - Poly[[diaqua-bis-(2,2'-bipyridine)-bis-(MU(3)-5-hy-droxy-isophthalato)(MU(2)-5-hy droxy-isophthalato)digadolinium(III)] trihydrate]. AB - The asymmetric unit of the title coordination polymer, {[Gd(2)(C(8)H(4)O(5))(3)(C(10)H(8)N(2))(2)(H(2)O)(2)].3H(2)O}(n), contains two Gd(III) cations, one of which is surrounded by three 5-hy-droxy-isophthalate anions, one 2,2'-bipyridine ligand and two water mol-ecules in a distorted N(2)O(7) tricapped trigonal-prismatic coordination geometry. The other Gd cation is coordinated by four 5-hy-droxy-isophthalate anions and one 2,2'-bipyridine ligand in a distorted N(2)O(7) tricapped trigonal-prismatic coordination geometry. The 5-hy-droxy-isophthalate anions bridge the Gd cations, forming a layer structure. The layers are further connected by extensive O-H?O hydrogen bonding, assembling a three-dimensional supra-molecular network. PMID- 22058696 TI - catena-Poly[[dichloridozinc(II)]-MU-1,4-bis-(pyridin-2-ylmeth-oxy)benzene kappaN:N']. AB - In the title compound, [ZnCl(2)(C(18)H(16)N(2)O(2))](n), the Zn(II) ion is tetra hedrally coordinated by two Cl atoms and by two N atoms from different 1,4-bis (pyridin-2-ylmeth-oxy)benzene ligands. The ligand shows a non-planar configuration, in which the dihedral angles between the two terminal pyridine rings and the linking benzene ring are 7.86 (12) and 70.74 (11) degrees . The flexible ligand coordinates to the Zn(II) ions, generating an infinite chain propagating along [001]. PMID- 22058697 TI - (R,R(Fc),S(Ru))-Chlorido(eta-p-cymene){1-[1-(diphenyl-phosphanyl)ethyl]-2-[2 (diphenyl-phosphanyl)phenyl]ferrocene-kappaP,P'}ruthenium(II) hexa-fluorido phosphate. AB - The asymmetric unit of the title compound, [FeRuCl(C(5)H(5))(C(10)H(14))(C(37)H(31)P(2))]PF(6), contains two independent, geometrically similar Ru(II) complexes of a chiral ferrocenyldiphosphane with piano-stool coordination through the eta(6)-bound p-cymene ligand, two chelating phospho-rus donor atoms, and an exo-oriented chloride ion. The mean bond lengths of the two Ru complexes are Ru-C = 2.276 A, Ru-P = 2.3816 A, and Ru-Cl = 2.3924 A. Both chloride ligands form only intra-molecular C-H?Cl inter-actions. Seven weak inter-molecular C-H?F inter-actions involving mainly arene H atoms consolidate the crystal packing, which reveals an approximate c/2 pseudo translation relating the two independent Ru complex mol-ecules. PMID- 22058698 TI - MU-Acetato-aqua-MU-(5-bromo-2-{1,3-bis-[2-(5-bromo-2-oxidobenzyl-idene-amino)-eth yl]imidazolidin-2-yl}phenolato)methano-ldinickel(II) methanol disolvate monohydrate. AB - The crystal structure of the title compound, [Ni(2)(C(27)H(24)Br(3)N(4)O(3))(CH(3)CO(2))(CH(3)OH)(H(2)O)].2CH(3)OH.H(2)O contains [L(OAc){(CH(3)OH)Ni}{(H(2)O)Ni}] mol-ecules {H(3)L = 2-(5-bromo-2-hy droxy-phen-yl)-1,3-bis-[4-(5-bromo-2-hy-droxy-phen-yl)-3-aza-but-3-en-yl]-1,3 imidazolidine} with additional water and two methanol solvent mol-ecules. In this instance, one of the two Ni atoms is coordinated to a water and the other to a methanol mol-ecule. The Ni-O and Ni-N distances, as well as the angles about the metal atoms, show quite regular octa-hedra around the central ions. The Ni O(phenol)-Ni and Ni-O(acetate)-Ni angles are not similar [95.26 (13) and 97.34 (13) degrees , respectively], indicating that this subtle solvate exchange induces significant differences in the conformation adopted. The coordinated methanol ligand is involved in an intra-molecular hydrogen bond to the uncoordinated O atom of the bridging acetate ligand, while the coordinated water mol-ecule forms a hydrogen bond with the one of the methanol solvent mol-ecules. The water solvent mol-ecule forms strong hydrogen bonds to both phenolate O atoms. The remaining methanol solvent mol-ecule also forms a hydrogen bond with this solvent water mol-ecule. PMID- 22058699 TI - catena-Poly[[(triphenyl-phosphane)copper(I)]-di-MU-iodido-[(triphenyl phosphane)copper(I)]-MU-{1,2-bis-[1-(pyridin-4-yl)ethyl-idene]hydrazine}]. AB - In the title coordination polymer, [Cu(2)I(2)(C(14)H(14)N(4))(C(18)H(15)P)(2)](n), the Cu(I) atom is coordinated by two I atoms, one P atom and one N atom in a fairly regular tetra-hedral arrangement. A crystallographic inversion centre generates a Cu(2)I(2) diamond with a Cu-Cu separation of 3.0120 (5) A. The complete N,N'-(1-pyridin-4-yl ethethyl-idene)-hydrazine mol-ecule is also generated by inversion symmetry, and this bridging ligand leads to [011] polymeric chains in the crystal structure. PMID- 22058700 TI - Dichlorido{2-[(thio-phen-2-ylmeth-yl)imino-meth-yl]pyridine kappaN,N'}palladium(II). AB - In the title compound, [PdCl(2)(C(11)H(10)N(2)S)], the Pd(II) ion is four coordinated in a distorted square-planar environment by two N atoms of the chelating 2-[(thio-phen-2-ylmeth-yl)imino-meth-yl]pyridine ligand and two chloride anions. The thio-phene ring is rotationally disordered over two orientations in a 1:1 ratio. The crystal packing exhibits weak inter-molecular C H?Cl and C-H?S hydrogen bonds. PMID- 22058701 TI - Bis(3-benzoyl-1,1-di-sec-butyl-thio-ureato-kappaO,S)palladium(II). AB - The complex mol-ecule of the title complex, [Pd(C(16)H(23)N(2)OS)(2)], is completed by crystallographic twofold symmetry with the metal atom lying on the rotation axis. The Pd(II) atom exists within a slightly distorted square-planar geometry defined by a cis-O(2)S(2) donor set. The dihedral angle formed between the mean planes of the symmetry-related six-membered chelate rings is 12.88 (7) degrees and the bond lengths within the rings are indicative of significant electron delocalization. In the crystal, mol-ecules aggregate into dimers linked by four C-H?O inter-actions. PMID- 22058702 TI - Di-MU-chlorido-bis-[diacetonitrile-chlorido-oxidovanadium(IV)]. AB - The title compound, [V(2)Cl(4)O(2)(CH(3)CN)(4)], is a centrosymmetric dinuclear V(IV) complex associated with four mol-ecules of acetonitrile. The coordination around both V(IV) atoms is essentially square-planar, involving three Cl atoms and one O atom [maximum deviation = 0.017 (3) A for the O atom]. The augmented octahedral coordination of the metal atom is completed by the N atoms of acetonitrile ligands. The V(IV) atoms are linked by two Cl atoms, acting as bridging atoms. The crystal studied was a non-merohedral twin with a ratio of the two twin components of 0.8200 (3):0.1800 (3). Although Cl and O atoms are present as potential acceptors in the title compound, no hydrogen bonds were observed in the crystal structure. PMID- 22058703 TI - Tris(2,2'-bi-1H-imidazole-kappaN,N)cobalt(II) hydrogen phosphate. AB - The title compound, [Co(C(6)H(6)N(4))(3)]HPO(4), was synthesized under hydro thermal conditions. In the cation, the Co(II) atom is octa-hedrally coordinated by six N atoms from three 2,2'-bi-1H-imidazole ligands [Co-N bond lengths are in the range 2.084 (5)-2.133 (6) A]. Inter-molecular N-H?O hydrogen bonds form an extensive hydrogen-bonding network, which links cations and anions into a three dimensional crystal structure. PMID- 22058704 TI - Tetra-kis(MU-2-phen-oxy-propionato)-kappaO,O':O';kappaO:O,O';kappaO:O'-bis-[(1,10 phenanthroline-kappaN,N')(2-phen-oxy-propionato-kappaO,O')holmium(III)]. AB - The title compound, [Ho(2)(C(9)H(9)O(3))(6)(C(12)H(8)N(2))(2)], lies about a centre of symmetry and is comprised of six 2-phen-oxy-propionate (POPA) anions and two 1,10-phenanthroline (phen) ligands. The two Ho(III) ions are linked by four POPA groups utilizing both bi- and tridentate bridging modes to form an inversion-symmetric dimer. Each Ho(III) ion is nine-coordinate, with a chelating 1,10-phenanthroline mol-ecule, one bidentate chelating carboxyl-ate group, two bidentate bridging carboxyl-ate groups and two tridentate bridging carboxyl-ate groups in a distorted mono-capped square anti-prism geometry. There are weak pi pi aromatic inter-actions between the phen groups and aromatic rings of the POPA ligands [centroid-centroid distance = 3.829 (1) A]. PMID- 22058705 TI - A new mono-functionalized organoimido hexa-molybdate derivative: bis-(tetra-n butyl-ammonium) (5-chloro-2-methyl-phenyl-imido)-MU(6)-oxido-dodeca-MU(2)-oxido penta-oxidohexa-molybdate(VI). AB - The title complex, [(C(4)H(9))(4)N](2)[Mo(6)(C(7)H(6)ClN)O(18)], was prepared by the reaction of (Bu(4)N)(4)[alpha-Mo(8)O(26)] and 2-methyl-5-chloro-aniline hydro chloride with N,N'-dicyclo-hexyl-carbodiimide as dehydrating agent in dry acetonitrile solution. The aryl-imido ligand is linked to an Mo atom of the Lindqvist-type hexamolybdate anion by an Mo N triple bond, with a bond length of 1.732 (4) A and an Mo N-C bond angle of 169.1 (4) degrees , typical for monodentate imido groups in such hybrid complexes. Due to the inter-action between one H atom in the aryl group and an O atom of a symmetry-related hexa molybdate cluster, the anions form centrosymmetric dimers in the crystal structure. Weak C-H?O contacts are observed between the cations and anions. Unresolved disorder in some of the butyl chains of the ammonium cation is noted. PMID- 22058706 TI - Diiodidobis{4-[2-(2-methyl-phen-yl)ethen-yl]pyridine-kappaN}cadmium. AB - In the title complex, [CdI(2)(C(14)H(13)N)(2)], the Cd atom lies on a twofold rotation axis that relates the I atom and the 4-(2-methyl-styr-yl)pyridine ligand to their counterparts. Therefore the asymmetric unit contains one crystallographically independent half-mol-ecule. The Cd atom adopts a tetra hedral coordination geometry, coordinated by two I atoms and two N atoms from the symmetry-related 4-(2-methyl-styr-yl)pyridine ligands. PMID- 22058707 TI - Bis(9-amino-acridinium) bis-(pyridine-2,6-dicarboxyl-ato-kappaO,N,O)manganate(II) trihydrate. AB - The asymmetric unit of the title compound, (C(13)H(11)N(2))(2)[Mn(C(7)H(3)NO(4))(2)].3H(2)O, consists of a discrete mononuclear [Mn(2,6-pydc)(2)](2-) anionic complex (2,6-pydc is pyridine-2,6 dicarboxyl-ate) associated with two 9-amino-acridinium counter-ions for neutralization of charge and three uncoordin-ated water mol-ecules. The Mn(II) atom is six-coordinated by (2,6-pydc)(2-) anions in a tridentate fashion and is at the centre of a distorted octa-hedron formed by the MnO(4)N(2) bonding set. In the crystal, various inter-molecular inter-actions between different moieties can be found, such as different kinds of hydrogen bonds, offset or slipped pi-pi [centroid-centroid distances in the range 3.3704 (12) to 3.8674 (13)A] and C=O?pi [3.563 A] inter-actions, which lead to the formation of a three-dimensional supra molecular network. PMID- 22058708 TI - Di-MU(3)-chlorido-tetra-MU(2)-chlorido-dichloridobis(dimethyl-formamide kappaO)hexa-kis-(1H-imidazole-kappaN)tetra-cadmium. AB - The centrosymmetric mol-ecule of the title complex, [Cd(4)Cl(8)(C(3)H(4)N(2))(6)(C(3)H(7)NO)(2)], contains four Cd(II) atoms, six imidazole, two dimethyl-formamide and eight chloride ligands. The structure shows a novel chloride-bridged tetra-nuclear cadmium quasi-cubane cluster. The coordination geometry of all Cd(II) atoms is distorted octa-hedral, with the two metal atoms in the asymmetric unit in different coordination environments. One of the Cd(2+) ions is coordinated by five Cl(-) ions and by one N atom from an imidazole ligand, while the second is coordinated by three chloride ligands, two N atoms from two imidazole ligands and one O atom from a dimethyl-formamide mol ecule. Inter-molecular N-H?Cl hydrogen bonds link the mol-ecules into a two dimensional polymeric structure parallel to the ab plane. PMID- 22058709 TI - Bis(MU-azido-kappaN:N)bis-{(acetato-kappaO,O')[2,4,6-tris-(2-pyrid-yl)-1,3,5 triazine-kappaN,N,N]lead(II)}. AB - The complete dinuclear title complex, [Pb(2)(C(2)H(3)O(2))(2)(N(3))(2)(C(18)H(12)N(6))(2)], is generated by the application of a crystallographic centre of inversion. The Pb(II) atom is coordinated by three N atoms of the tridentate ligand, two O atoms derived from an asymmetrically coordinating acetate ligand, and two azido-N atoms derived from two asymmetrically bridging azido ligands. The metal coordination geometry can be described as a square anti-prism with one position occupied by an unseen lone pair of electrons. In the ligand, the two coordinating pyridine rings are almost co-planar with the central pyrazine ring [dihedral angles = 0.47 (17) and 0.83 (18) degrees ], but the terminal ring is twisted [dihedral angle = 19.76 (18) degrees ]. In the crystal, the presence of pi-pi inter-actions [ring centroid distance between pyridyl rings = 3.581 (2) A] leads to supra-molecular chains along the a-axis direction. PMID- 22058710 TI - Tetra-kis(5,7-dimethyl-quinolin-8-olato-kappaN,O)hafnium(IV) dimethyl-formamide disolvate. AB - In the title compound, [Hf(C(11)H(10)NO)(4)].2C(3)H(7)NO, the Hf(IV) atom is coordinated by four N,O-donating bidentate 5,7-dimethyl-8-quinolino-late (Ox(-)) ligands arranged to give a distorted square-anti-prismatic coordination polyhedron. The average Hf-O and Hf-N distances are 2.098 and 2.298 A, respectively, and the average O-Hf-N bite angle is 70.2 degrees . The crystal packing is controlled by pi-pi inter-actions between Ox(-) ligands of neighbouring mol-ecules, giving rise to a three-dimensional supra-molecular grid network. The inter-planar distances vary from 3.441 (1) to 3.509 (1) A, while the centroid-centroid distances vary from 3.688 (2) to 3.759 (12) A. A non-classical C-H?O hydrogen bond is observed between the complex and one of the solvate mol ecules. PMID- 22058711 TI - Diaqua-bis-(5-methyl-pyrazine-2-carboxyl-ato-kappaN,O)cobalt(II) dihydrate. AB - In the title complex, [Co(C(6)H(5)N(2)O(2))(2)(H(2)O)(2)].2H(2)O, the coordination geometry of the Co(2+) cation is distorted octa-hedral, with two N atoms and two O atoms from two 5-methyl-pyrazine-2-carboxyl-ate ligands in the equatorial plane. The two remaining coordination sites are occupied by two water mol-ecules. In addition, there are two uncoordinated water mol-ecules in the asymmetric unit. The crystal structure is stabilized by a network of O-H?O and O H?N hydrogen-bonding inter-actions, forming a three-dimensional structure. PMID- 22058712 TI - Poly[diaquabis-(MU(4)-fumarato-kappaO:O:O:O)(MU(4)-fumarato kappaO:O,O:O:O,O)(MU(2)-fumaric acid-kappaO:O)dipraseodymium(III)]. AB - The title complex, [Pr(2)(C(4)H(2)O(4))(3)(C(4)H(4)O(4))(H(2)O)(2)](n), was synthesized by reaction of praseodymium(III) nitrate hexa-hydrate with fumaric acid in a water-ethanol (4:1) solution. The asymmetric unit comprises a Pr(3+) cation, one and a half fumarate dianions (L(2-)), one half-mol-ecule of fumaric acid (H(2)L) and one coordinated water mol-ecule. The carboxyl-ate groups of the fumarate dianion and fumaric acid exhibit different coordination modes. In one fumarate dianion, two carboxyl-ate groups are chelating with two Pr(3+) cations, and the other two O atoms each coordinate a Pr(3+) cation. Each O atom of the second fumarate dianion binds to a different Pr(3+) cation. The fumaric acid employs one O atom at each end to bridge two Pr(3+) cations. The Pr(3+) cation is coordinated in a distorted tricapped trigonal-prismatic environment by eight O atoms of fumarate dianion or fumaric acid ligands and one water O atom. The PrO(9) coordination polyhedra are edge-shared through one carboxyl-ate O atom and two carboxyl-ate groups, generating infinite praseodymium-oxygen chains, which are further connected by the ligands into a three-dimensional framework. The crystal structure is stabilized by O-H?O hydrogen-bond inter-actions between the coordin-ated water mol-ecule and the carboxyl-ate O atoms. PMID- 22058713 TI - Poly[trans-diaquabis-[MU(2)-2-(pyridin-3-yl)acetato-kappaN:O]-zinc]. AB - In the title coordination polymer, [Zn(C(7)H(6)NO(2))(2)(H(2)O)(2)](n), the Zn(II) cation is located on an inversion center and is coordinated by four pyridyl-acetate anions and two water mol-ecules in a distorted ZnN(2)O(4) octa hedral geometry. The pyridine-N and carboxyl-ate-O atoms of the pyridyl-acetate anion connect to two Zn(II) cations, forming a two-dimensional polymeric complex extending parallel to (212). Inter-molecular O-H?O and weak C-H?O hydrogen bonding is present in the crystal structure. PMID- 22058714 TI - MU-Oxalato-bis-[bis-(2,2'-bipyridine)-manganese(II)] bis(perchlorate) 2,2' bipyridine solvate. AB - The unit cell of the title compound, [Mn(2)(C(2)O(4))(C(10)H(8)N(2))(4)](ClO(4))(2).C(10)H(8)N(2), consists of a binuclear cation, two perchlor-ate anions, and one solvent 2,2'-bipyridine (bpy) mol-ecule. In the complex cation [Mn(2)(C(2)O(4))(C(10)N(2)H(8))(4)](2+), two Mn(II) atoms are bridged by a bis-(bidentate) oxalate ligand, each Mn(II) atom being further coordinated by two bpy ligands in a distorted octa-hedral geometry. The distance between the two six-coordinated metal atoms is 5.583 (1) A. pi-pi stacking inter-actions [inter-planar distances between bpy rings = 3.739 (1) A] are essential to the supramolecular assembly. There are extensive inter-ionic C H?O inter-actions between the cations and between the cation and anion. Three of the four perchlorate O atoms are disordered over two sets of sites with occupancy ratios of 0.852 (6):0.148 (6). PMID- 22058715 TI - {5,5'-Dimeth-oxy-2,2'-[1,1'-(2,2-dimethyl-propane-1,3-diyldinitrilo)-diethyl idyne]diphenolato-kappaO,N,N',O'}copper(II) monohydrate. AB - The tetra-dentate dianion in the title complex hydrate, [Cu(C(23)H(28)N(2)O(4))].H(2)O, provides the Cu(II) atom with a cis-N(2)O(2) donor set. There is a significant twist from a regular square-planar geometry with the dihedral angle formed between the two six-membered CuOC(3)N chelate rings being 32.14 (8) degrees . The water mol-ecule forms hydrogen bonds to each of the coordinating O atoms of a given complex mol-ecule. Supra-molecular layers in the bc plane are formed in the crystal packing through C-H?O and C-H?pi inter actions. PMID- 22058716 TI - Acetyl-ferrocene-2-chloro-1-ferrocenyl-ethanone (1/1). AB - In the title co-crystal, [Fe(C(5)H(5))(C(7)H(6)ClO)][Fe(C(5)H(5))(C(7)H(7)O)], both substituted ferrocene mol-ecules show the expected sandwich structure. The crystal packing exhibits weak inter-molecular Cl?Cl contacts of 3.279 (4) A, pi pi inter-actions between the substituted Cp rings of two neighbouring 2-chloro-1 ferrocenyl-ethanone mol-ecules [centroid-centroid distance = 3.534 (3) A], and weak inter-molecular C-H?O and C-H?Cl hydrogen bonds. PMID- 22058717 TI - [Mn(bpb)(DMAP)(NO)], an {Mn-NO} nitrosyl with Z' = 8. AB - The structure of the title compound octa-kis-{[4-(dimethyl-amino) pyridine](nitros-yl)[N,N'-(o-phenyl-ene)bis-(pyridine-2 carboxamidato)]manganese(II)} ethanol hepta-solvate 3.5-hydrate, [Mn(C(18)H(12)N(4)O(2))(C(7)H(10)N(2))(NO)](8).7C(2)H(5)OH.3.5H(2)O, or 8[Mn(bpb)(DMAP)(NO)].7EtOH.3.5H(2)O, is an unusual example of a structure with Z' = 8. The tetra-dentate bpb ligand, together with the nitrosyl and dimethyl-amino pyridine ligands, gives rise to a distorted octa-hedral coordination environment for the Mn(II) ion. The average Mn-N((N=O)) bond length is 1.631 (13) A. The eight mol-ecules in the asymmetric unit differ mainly in the rotation of the DMAP pyridine plane with respect to a reference plane of the Mn and three N atoms, one of which is the N atom of the NO group. The dihedral angles between the normals to these planes range from a minimum of 28.0 (2) degrees to a maximum of 64.2 (2) degrees . There are also some differences in O-H?O hydrogen bonding inter actions. For example, of the sixteen C=O acceptors, there are seven different inter-actions with EtOH donors and two inter-actions with H(2)O donors. The crystal studied was found to be a two-component twin, with a 179.9 degrees rotation about the real axis [-0.535, 0.004, 1.000]. Due to the presence of a superlattice and, consequently, the large number of weak reflections, the refinement utilized rigid solvate groups and isotropic displacement parameters for all except the Mn atoms. H atoms were not located for hydrate molecules. PMID- 22058718 TI - catena-Poly[[MU(2)-aqua-diaqua-bis-(MU(4)-pyridazine-3,6-dicarboxyl-ato)tetra lithium] monohydrate]. AB - In the polymeric structure of the title compound {[Li(2)(C(6)H(2)N(2)O(4))(2)Li(H(2)O)(2)Li(H(2)O)].H(2)O}(n), the coordination of two independent Li(I) ions is distorted trigonal-bipyramidal and that of the other two independent Li(I) ions is distorted tetra-hedral. The former two Li(I) ions are bridged by hetero-ring N atoms of two independent pyridazine-3,6 dicarboxyl-ate ligands, making a dimeric moiety. The carboxyl-ato-O atoms of both bidentate ligands bridge the dimers to adjacent independent aqua-coordinated Li(I) ions, forming mol-ecular ribbons. The latter are bridged by ligand carboxyl ato and aqua O atoms, forming mol-ecular layers parallel to (100) which are held together by an extended system of O-H?O hydrogen bonds. PMID- 22058719 TI - Tetra-aqua-bis-(2-{[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]sulfan-yl}acetato) iron(II). AB - In the title compound, [Fe(C(9)H(6)N(3)O(3)S)(2)(H(2)O)(4)] or [Fe(POA)(2)(H(2)O)(4)], the Fe(II) atom is located on an inversion center and is ligated by four O atoms of coordinated water mol-ecules in the equatorial plane while two POA ligands acting as monodentate ligands occupy the axial positions through their pyridyl N atoms, completing a slightly distorted octa-hedral coordination geometry. A three-dimensional supra-molecular network is formed by multiple O-H?O hydrogen-bonding inter-actions between the coordinated water donors and the uncoordinated carboxyl acceptors. PMID- 22058720 TI - catena-Poly[iron(II)-bis-{MU-5-carb-oxy-2-[(1H-1,2,4-triazol-1-yl)meth-yl]-1H imidazole-4-carboxyl-ato}]. AB - In the title coordination polymer, [Fe(C(8)H(6)N(5)O(4))(2)](n) {or [FeL(2)](n),where HL = 2-[(1H-1,2,4-triazol-1-yl) meth-yl]-1H-imidazole-4,5 dicarb-oxy-lic acid)}, the Fe(II) ion, located on an inversion centre, is six coordinated by two O atoms and four N atoms from two L(-) ligands in a distorted octa-hedral geometry [Fe-O = 2.1452 (13), Fe-N = 2.1316 (14) and 2.2484 (15) A]. There is an intra-molecular O-H?O hydrogen bond in each L(-) ligand. Being an effective tridentate bridging ligand, the deprotonated L(-) anions link two Fe(II) atoms, yielding a chain-like polymer propagating along [100]. In the crystal, these polymer chains are linked via N-H?N hydrogen bonds, forming a two dimensional network. PMID- 22058721 TI - Poly[tris-(MU(3)-2-amino-ethane-sulfonato)-cobalt(II)potassium]. AB - The title compound, [CoK(C(2)H(6)NO(3)S)(3)](n), is isotypic with its Ni(II) analogue. The Co(II) atom is chelated by the three taurinate ligands in a distorted octa-hedral geometry and in a facial manner. Each taurinate ligand bridges two K(+) ions via its sulfonate group, forming a three-dimensional framework. Weak N-H?O hydrogen bonding is observed in the crystal structure. PMID- 22058722 TI - Disodium diaqua-bis-(methyl-enedi-phos-pho-nato-kappaO,O')cobaltate(II) dihydrate. AB - In the title compound, Na(2)[Co(CH(4)O(6)P(2))(2)(H(2)O)(2)].2H(2)O, the asymmetric unit is composed of one methyl-enediphospho-nate ligand and one water mol-ecule, which both are coordinated to a Co(II) atom, as well as a non coordinated water mol-ecule and a sodium cation. The Co(II) atom occupies a special position on a crystallographic inversion centre. The slightly distorted Co(II)O(6) octa-hedral coordination environment is composed of two bidentate methyl-enediphospho-nate ligands and two coordinated water mol-ecules in trans positions. The sodium ion is octa-hedrally coordinated to six O atoms with Na-O distances ranging from 2.3149 (12) to 2.6243 (12) A. An extensive three dimensional network of inter-molecular as well as intra-molecular O-H?O and C-H?O hydrogen bonding inter-acions is present. PMID- 22058723 TI - Bis(4-amino-benzoato)-kappaO,O';kappaO-(2,2'-bipyridine-kappaN,N')zinc. AB - In the title complex, [Zn(C(7)H(6)NO(2))(2)(C(10)H(8)N(2))], the Zn(II) cation is coordinated by two amino-benzoate anions and one 2,2'-bipyridine ligand in a distorted trigonal-bipyramidal geometry. The carboxyl-ate group of one aminobenzoate anion coordinates to the Zn(II) cation in a monodentate manner, whereas the carboxyl-ate group of the other amino-benzoate anion chelates the Zn cation with different Zn-O bond lengths. Inter-molecular N-H?N and N-H?O hydrogen bonding is present in the crystal structure. PMID- 22058724 TI - Poly[[[MU(2)-1,1'-(butane-1,4-di-yl)bis-(1H-imidazole)-kappaN:N](MU(2)-2,6-di methyl-pyridine-3,5-dicarboxyl-ato-kappaO:O)zinc] dihydrate]. AB - In the title coordination polymer, {[Zn(C(9)H(7)NO(4))(C(10)H(14)N(4))].2H(2)O}(n), the Zn(II) ion displays a distorted tetra-hedral geometry with two imidazole N atoms from two 1,1'-(butane 1,4-di-yl)bis-(imidazole) (bbi) ligands and two carboxyl-ate O atoms from two 2,6 dimethyl-pyridine-3,5-dicarboxyl-ate (dpdc) ligands. The bbi and dpdc ligands bridge the Zn(II) ions, forming layers parallel to (011). O-H?O and O-H?N hydrogen bonds and pi-pi inter-actions between the imidazole rings [centroid centroid distance = 3.807 (5) A] connect the layers. Two of the three uncoordinated water mol-ecules are disordered, each over two 0.25-occupancy positions. PMID- 22058725 TI - Poly[[diaquabis(2,2'-bipyridine-kappaN,N')(MU(3)-5-hydroxyisophthalato kappaO,O:O,O:O)(MU(3)-5-hydroxy-isophthalato-kappaO,O:O:O)(MU(2)-5 hydroxyisophthalato-kappaO,O:O)didysprosium(III)] dihydrate]. AB - The polymeric title compound, {[Dy(2)(C(8)H(4)O(5))(3)(C(10)H(8)N(2))(2)(H(2)O)(2)].2H(2)O}(n), contains two independent Dy(III) ions, both of which are nine-coordinated in a distorted tricapped trigonal-prismatic geometry. One Dy(III) ion is coordinated by five 5 hy-droxy-isophthalate (hip) ligands and one 2,2'-bipyridine (bpy) ligand and the other by three hip ligands, one bpy ligand and two water mol-ecules. The Dy(III) ions are bridged by the carboxyl-ate groups of the hip ligands, forming a three dimensional framework. O-H?O hydrogen bonds are present in the crystal structure. PMID- 22058726 TI - Bis(triphenyl-lambda-phosphanylidene)ammonium hydrogen dichloride. AB - In the title compound, [(Ph(3)P)(2)N](+).[Cl-H-Cl](-) or C(36)H(30)NP(2) (+).Cl(2)H(-), the H atom of the [Cl-H-Cl](-) anion and the N atom of the [(Ph(3)P)(2)N](+) cation are located on a twofold axis, yielding overall symmetry 2 for both the cation and the anion. The central P-N-P angle [144.12 (13) degrees ] of the cation is in the expected range and indicates only weak cation-anion inter-actions. The almost linear [Cl-H-Cl](-) anion is a rare example of a symmetric hydrogen bridge in a hydrogen dichloride anion. The Cl?Cl distance and two equal Cl-H bonds are typical of such a symmetric hydrogen dichloride anion. PMID- 22058727 TI - 4-Dimethyl-amino-N'-(2-hy-droxy-3,5-diiodo-benzyl-idene)benzohydrazide. AB - The title mol-ecule, C(16)H(15)I(2)N(3)O(2), adopts an E configuration about the C=N bond. The dihedral angle between the two benzene rings is 6.4 (2) degrees . An intra-molecular O-H?N hydrogen bond occurs. In the crystal, mol-ecules are linked through inter-molecular N-H?O hydrogen bonds, forming chains propagating in the c-axis direction. PMID- 22058728 TI - 6-Benzyl-2-[(triphenyl-lambda-phosphanyl-idene)amino]-4,5,6,7-tetra-hydro thieno[2,3-c]pyridine-3-carbonitrile. AB - In the title compound, C(33)H(28)N(3)PS, the P atom has a distorted tetra-hedral PNC(3) environment, formed by the N atom and three aryl rings. No inter-molecular hydrogen-bonding inter-actions or pi-pi stacking inter-actions are present in the crystal structure. PMID- 22058729 TI - 6-Chloro-3-(3-methyl-phen-yl)-1,2,4-triazolo[4,3-b]pyridazine. AB - The title compound, C(12)H(9)ClN(4), was prepared from dichloro-pyridazine and tolyl-tetra-zole in a nucleophilic biaryl coupling followed by thermal ring transformation. The mol-ecule is essentially planar (r.m.s. deviation for all non H atoms = 0.036 A) and an intra-molecular C-H?N hydrogen bond occurs. In the crystal, the mol-ecules form dimers connected via pi-pi inter-actions [centroid centroid distance = 3.699 (2) A], which are further connected to neighbouring mol ecules via C-H-N bonds. The bond lengths in the pyridazine ring system indicate a strong localization of the double bonds and there is a weak C-Cl bond [1.732 (3) A]. PMID- 22058730 TI - 2-Phenyl-3-(trimethyl-sil-yl)propan-1-aminium chloride. AB - The title compound, C(12)H(22)NSi(+).Cl(-), contains two formula units in the asymmetric unit and is a hydro-chloride salt in which the amine N atom is protonated and the NH(3) (+) group forms hydrogen bonds with the Cl(-) anion, forming a ribbon in the c-axis direction. PMID- 22058731 TI - 2,2'-Bipyrimidine-1,1'-diium bis-(tri-iodide)-2,2'-bipyrimidine-water (1/2/2). AB - In the crystal of the title compound, C(8)H(8)N(4) (2+).2I(3) ( ).2C(8)H(6)N(4).2H(2)O, inversion centres are located at the centroids of the central C-C bonds of the cation and the bpym mol-ecules, as well as at the central I atoms of both anions. Inter-molecular O-H?N and N-H?O hydrogen bonds are observed in the crystal structure. PMID- 22058732 TI - N,N-Dimethyl-5-nitro-N,N-diphenyl-pyrimidine-4,6-diamine. AB - In the title compound, C(18)H(17)N(5)O(2), the pyrimidine ring makes dihedral angles of 66.09 (12), 71.39 (13) and 56.7 (3) degrees with two phenyl rings and the nitro group, respectively. The dihedral angle between the two phenyl rings is 44.05 (14) degrees . PMID- 22058733 TI - 3-{[(Benz-yloxy)carbon-yl]amino}-butanoic acid. AB - In the title compound, C(12)H(15)NO(4), the butyric acid group has a stretched trans conformation. The dihedral angle between the phenyl ring and the oxycarb oxy-amino N-(C=O)-O-C plane is 56.6 (2) degrees . In the crystal, an inversion dimer is formed by a pair of O-H?O hydrogen bonds. The dimers are further linked by N-H?O hydrogen bonds between amide groups, forming a tape along the b axis. PMID- 22058734 TI - 2-Imino-3-(2-nitro-phen-yl)-1,3-thia-zolidin-4-one. AB - In the title compound, C(9)H(7)N(3)O(3)S, the nitro and thia-zolidinone moieties are inclined with respect to the aromatic ring at dihedral angles of 9.57 (16) and 78.42 (4) degrees , respectively. In the crystal, N-H?O hydrogen bonding connects the mol-ecules along the c and a axes to form a two-dimensional polymeric network. A weak S?O inter-action [3.2443 (11) A] and phenyl ring to phenyl ring off-set pi?pi stacking [with centroid-centroid separation of 3.6890 (7) A and ring slippage of 1.479 A] link the polymeric chains along the b and a axes, respectively. PMID- 22058735 TI - 4,6,10,12,16,18,22,24-Octa-O-methyl-2,8,14,20-tetra-pentylresorcin[4]arene. AB - The complete molecule of the title compound, C(56)H(80)O(8), is generated by a crystallographic inversion centre. The dihedral angle between the aromatic ring and the unique half of the molecule is 81.52 (16) degrees . There are no pi-pi inter-actions in the crystal structure. PMID- 22058736 TI - Hexane-1,6-diaminium bis-[3,4,5,6-tetra-bromo-2-(meth-oxy-carbon-yl)benzoate] methanol disolvate. AB - In the title compound, C(6)H(18)N(2) (2+).2C(9)H(3)Br(4)O(4) (-).2CH(4)O, the carboxyl-ate and meth-oxy-carbonyl groups in one of the anions form dihedral angles of 71.9 (3) and 60.7 (3) degrees , respectively, with the aromatic ring while in the other anion these angles are 68.4 (3) and 56.8 (3) degrees , respectively. In the crystal, the constituent units are linked into a two dimensional network parallel to the ab plane by N-H?O and O-H?O hydrogen bonds. PMID- 22058737 TI - Ethyl 2-[2-(2-meth-oxy-phen-yl)hydrazinyl-idene]-3-oxobutano-ate. AB - In the title compound, C(13)H(16)N(2)O(4), an intra-molecular N-H?O hydrogen bond generates an S(6) ring. The mol-ecule adopts an E configuration with respect to the central C=N double bond. In the crystal, symmetry-related mol-ecules are connected into chains along [010] via weak C-H?N hydrogen bonds. The crystal structure is further stabilized by weak C-H?pi inter-actions. PMID- 22058738 TI - 2-Amino-4,6-dimethyl-pyridinium chloride dihydrate. AB - In the title hydrated mol-ecular salt, C(7)H(11)N(2) (+).Cl(-).2H(2)O, the pyridine N atom of the 2-amino-4,6-dimethyl-pyridine mol-ecule is protonated. The cation is essentially planar, with a maximum deviation of 0.006 (2) A. In the crystal, the components are linked by N-H?O, N-H?Cl and O-H?Cl hydrogen bonds, thereby forming sheets lying parallel to (100). The crystal structure is further stabilized by aromatic pi-pi stacking inter-actions between the pyridinium rings [centroid-centroid distance = 3.4789 (9) A]. PMID- 22058739 TI - Quinoline-2-carbaldehyde. AB - The title compound, C(10)H(7)NO, crystallizes with two almost planar mol-ecules (A and B) in the asymmetric unit (r.m.s. deviations = 0.018 and 0.020 A). In the crystal, the A mol-ecules are linked by weak C-H?O inter-actions, thereby generating C(9) [001] chains. The B mol-ecules do not exhibit any directional bonding inter-actions. PMID- 22058740 TI - N-(4-Chloro-phen-yl)-4-ethyl-piperazine-1-carboxamide. AB - In the title mol-ecule, C(13)H(18)ClN(3)O, the piperazine ring has a chair conformation. In the crystal, mol-ecules are linked into chains along [100] by N H?O hydrogen bonds. PMID- 22058741 TI - N-(4-Chloro-phen-yl)-4-(pyrimidin-2-yl)piperazine-1-carboxamide. AB - The title compound, C(15)H(16)ClN(5)O, contains two mol-ecules, A and B, in the asymmetric unit, in which the dihedral angles between the terminal aromatic rings are 42.41 (17) and 45.77 (18) degrees . The central six-membered ring in both mol ecules has a chair conformation with equatorial substituents. In the crystal, mol ecules are linked into [100] C(4) chains of alternating A and B mol-ecules by N H?O hydrogen bonds. PMID- 22058742 TI - (3Z)-3-Hydrazinylideneindolin-2-one. AB - The title mol-ecule, C(8)H(7)N(3)O, is almost planar, with a maximum deviation of 0.0232 (2) A from the least-squares plane. The Z conformation of the C=N double bond is stabilized by an intra-molecular N-H?O hydrogen bond. In the crystal, adjacent mol-ecules are linked by inter-molecular N-H?N and N-H?O hydrogen bonds, forming zigzag sheets parallel to the c axis; the sheets are further stabilized by pi-pi inter-actions [centroid-centroid distance = 3.7390 (10) A]. PMID- 22058743 TI - (E)-N-(Anthracen-9-yl-methyl-idene)-4-nitro-aniline. AB - In the title molecule, C(21)H(14)N(2)O(2), the anthracenyl system is approximately planar [maximum deviation = 0.056 (4) A] and is oriented at a dihedral angle of 73.6 (1) degrees with respect to the benzene ring. An intra molecular C-H?N hydrogen bond generates an S(6) ring motif. The crystal packing is stabilized by C-H?pi and pi-pi inter-actions [centroid-centroid distances of 3.688 (2), 3.656 (1) and 3.716 (2) A]. PMID- 22058744 TI - 1-(4-Methyl-benzo-yl)-3-{2-[3-(4-methyl-benzo-yl)thio-ureido]phen-yl}thio-urea. AB - In the title compound, C(24)H(22)N(4)O(2)S(2), the dihedral angles formed by the thio-ureido groups with the attached benzene ring are 43.81 (13) and 75.25 (13) degrees . The dihedral angle between the thio-ureido groups is 85.48 (10) degrees . The mol-ecule is stabilized by intra-molecular N-H?S, N-H?O and C-H?S hydrogen bonds. In the crystal, molecules are linked by intermolecular N-H?S hydrogen bonds together with C-H?pi inter-actions. PMID- 22058745 TI - (E)-Methyl N'-(3-hy-droxy-benzyl-idene)hydrazinecarboxyl-ate dihydrate. AB - The title compound, C(9)H(10)N(2)O(3).2H(2)O, crystallizes with two organic mol ecules and four water mol-ecules in the asymmetric unit. Both organic mol-ecules adopt a trans conformation with respect to the C=N bond and are close to planar [dihedral angles between the side chain and the aromatic ring = 9.34 (8) and 4.96 (8) degrees ]. In the crystal, the components are linked into three-dimensional network by N-H?O and O-H?O hydrogen bonds. PMID- 22058746 TI - 2-[(1H-Imidazol-2-yl)disulfan-yl]-1H-imidazole. AB - In the title molecule, C(6)H(6)N(4)S(2), a twofold rotation axis passes through the mid-point of the S-S bond. The C-S-S-C torsion angle is 83.62 (17) degrees . pi-pi stacking between imidazole rings of adjacent mol-ecules is observed in the crystal structure, the centroid-centroid distance being 3.447 (2) A. Inter molecular N-H?S hydrogen bonding results in the formation of a linear chain in the c-axis direction. PMID- 22058747 TI - 1,4-Dimethyl-2-phenyl-6,7-dihydro-1H-pyrazolo-[4,3-b]pyridine-3,5(2H,4H)-dione. AB - The mean plane of the pyrazolone ring [maximum deviation = 0.054 (1) A] of the title compound, C(14)H(15)N(3)O(2), is oriented at a dihedral angle of 36.05 (7) degrees with respect to the phenyl ring. The methyl group is slightly disposed [distance = 0.864 (2) A] out of the mean plane of the pyrazolone ring to which it is attached. PMID- 22058748 TI - 2-Meth-oxy-4-methyl-1-[1-(phenyl-sulfon-yl)propan-2-yl]benzene. AB - The title mol-ecule, C(17)H(20)O(3)S, displays a U-shaped structure; the two benzene rings are nearly parallel and partially overlapped to each other, the dihedral angle and centroid-to-centroid distance being 15.0 (2) degrees and 3.723 (2) A. In the crystal, weak inter-molecular C-H?O hydrogen bonds link the mol-ecules, forming supra-molecular chains running along the a axis. PMID- 22058749 TI - Hydrogen-bond inter-actions in morpholinium bromide. AB - In the title compound, C(4)H(10)NO(+).Br(-), which was synthesized by dehydration of diethano-lamine with HBr, morpholinium and bromide ions are linked into chains by N-H?Br hydrogen bonds describing a C(2) (1)(4) graph-set motif. Weaker bifurcated N-H?Br inter-actions join centrosymmetrically related chains through alternating binary graph-set R(4) (2)(8) and R(2) (2)(4) motifs, to form ladders along [100]. In addition, C-H?O inter-actions between centrosymmetric morpholinium cations link ladders, via[Formula: see text](8) motifs, to yield sheets parallel to (101), which in turn are crosslinked by weak C-H?O inter actions, related across a glide plane, to form a three-dimensional network. PMID- 22058750 TI - Tetra-n-butyl-ammonium bromide: a redetermination at 150 K addressing the merohedral twinning. AB - The redetermined, low temperature (150 K), structure of tetra-n-butyl-ammonium bromide, (C(4)H(9))(4)N(+).Br(-), has been found to be merohedrally twinned via twin law -1 0 0, 0 - 1 0, 1 0 1. The structure was previously determined, with low precision, no inclusion of H atoms and only the bromide ion refined with anisotropic displacement parameters, by Wang et al. (1995 ?). Mol. Cryst. Liq. Cryst. Sci. Tech. A, 264, 115-129. The redetermined structure has considerably improved precision in all geometrical parameters, has all non-H atoms refined anisotropically, H atoms included, and is isomorphous with the iodide analogue. The structure is otherwise routine, with the shortest cation to anion contacts being between the bromide anion and the CH atoms close to the ammonium nitro-gen centre at a distance of ca. 2.98-3.11 A. Each anion makes eight such contacts to four different anions. The n-butyl chains are fully extended, adopting an all anti conformation with approximate S(4) point symmetry. PMID- 22058751 TI - [3-(5-Hy-droxy-5H-dibenzo[a,d]cyclo-hepten-5-yl)prop-yl]dimethyl-ammonium 3 carboxyprop-2-enoate. AB - In the cation of the title salt, C(20)H(24)NO(+).C(4)H(3)O(4) (-), the N atom in the dimethyl-ammonium group is protonated. The dihedral angle between the mean planes of the two six-membered rings fused to the cyclo-hepten-5-yl ring is 54.4 (1) degrees . An intra-molecular O-H?O hydrogen bond occurs in the anion. The crystal packing is stabilized by inter-molecular O-H?O and N-H?(O,O) hydrogen bonds and weak C-H?O inter-actions, forming a two-dimensional network. PMID- 22058752 TI - N-(3-Chloro-4-fluoro-phen-yl)-2,2-diphenyl-acetamide. AB - In the title compound, C(20)H(15)ClFNO, the dihedral angles between the mean planes of the acetamide group and the chloro-fluoro-substituted benzene ring and the two phenyl rings are 10.8 (8), 81.9 (7) and 85.8 (5) degrees , respectively. The crystal packing is stabilized by N-H?O hydrogen bonds and weak C-H?O inter molecular inter-actions, forming infinite chains along the c axis. PMID- 22058753 TI - (3E,5E)-3,5-Dibenzyl-idene-1-phenethyl-piperidin-4-one. AB - In the title compound, C(27)H(25)NO, the piperidine ring adopts an envelope conformation with the N atom at the flap position. The two benzylidene-benzene rings are oriented at a dihedral angle of 8.5 (1) degrees . In the crystal, the mol-ecules are linked into centrosymmetric dimers by pairs of inter-molecular C H?O hydrogen bonds. The dimers are connected via C-H?pi inter-actions involving the phenyl rings. PMID- 22058754 TI - Ethyl 4-[3-(1H-imidazol-1-yl)propyl-amino]-3-nitro-benzoate. AB - In the title compound, C(15)H(18)N(4)O(4), the 1H-imidazole ring forms a dihedral angle of 67.12 (8) degrees with the benzene ring. An S(6) ring motif is formed via an intra-molecular N-H?O hydrogen bond. In the crystal, neighbouring mol ecules are linked by a pair of inter-molecular N-H?N hydrogen bonds, forming an inversion dimer. The dimers are further linked by a pair of C-H?O hydrogen bonds, leading to the formation of chain along [021]. A C-H?pi inter-action involving the centroid of the benzene ring is also observed between the chains. PMID- 22058755 TI - N-(4-Chloro-butano-yl)-N'-(2,5-dimeth-oxy-phen-yl)thio-urea. AB - The title mol-ecule, C(13)H(17)ClN(2)O(3)S, shows an anti and syn disposition of the butanoyl and 2,5-dimethoxyphenyl groups with respect to the thione and is stabilized by intra-molecular N-H?O and weak C-H?S hydrogen bonds. In the crystal, inter-molecular N-H?S hydrogen bonds link the mol-ecules into centrosymmetric dimers. The crystal structure is stabilized by weak C-H?O and C H?S contacts. PMID- 22058756 TI - 2-(6-Phenyl-7H-1,2,4-triazolo[3,4-b][1,3,4]thia-diazin-3-yl)-1,3-benzothia-zole. AB - In the title compound, C(17)H(11)N(5)S(2), the dihedral angles formed between the triazole ring and the benzene ring and the 1,3-benzothia-zole ring system are 8.67 (8) and 13.90 (9) degrees , respectively. The conformation of the triazolo thia-diazin-3-yl fused ring system is a twisted half-chair. Overall, the mol ecule adopts a flattened shape. Supra-molecular helical chains along the a axis sustained by C-H?N inter-actions are found in the crystal structure. These are linked via C-H?pi contacts as well as pi-pi [centroid-centroid distance = 3.5911 (12) A] inter-actions between the triazole and thia-zole rings. PMID- 22058757 TI - 1,7-Diethyl-4,10-diisopropyl-tetra-cene. AB - The mol-ecule of the title compound, C(28)H(32), is located on a crystallographic inversion center. The ethyl groups are essentially coplanar with the tetra-cene ring, making a torsion angle of -0.4 (4) degrees . The isopropyl groups adopt an asymmetric conformation with their terminal methyl groups positioned on opposite sides of the tetra-cene plane [the Me-C-C-C torsion angles are -22.5 (4) and 100.9 (3) degrees ]. In the crystal, the mol-ecules adopt an arrangement without significant pi-pi inter-actions along the stacking direction (y axis). PMID- 22058758 TI - N'-[(E)-2-Chloro-benzyl-idene]-2-[(1,3,4-thia-diazol-2-yl)sulfan yl]acetohydrazide. AB - In the title compound, C(11)H(9)ClN(4)OS(2), the thia-diazole and chloro-phenyl rings are oriented at an angle of 43.1 (1) degrees . The sum of the bond angles around the amide N atom (359.8 degrees ) of the acetohydrazide group is in accordance with a model of sp(2) hybridization. In the crystal, inversion dimers linked by pairs of N-H?O hydrogen bonds generate R(2) (2)(8) loops. Weak C-H?pi inter-actions also occur. PMID- 22058759 TI - 2-Methyl-1-phenyl-sulfonyl-1H-indole-3-carbaldehyde. AB - In the title compound, C(16)H(13)NO(3)S, the sulfonyl-bound phenyl ring forms a dihedral angle of 84.17 (6) degrees with the indole ring system. An intra molecular C-H?O hydrogen bond generates an S(6) ring motif. The crystal structure exhibits weak inter-molecular C-H?O hydrogen bonds and pi-pi inter-actions between the five- and six-membered rings of the indole group [centroid-centroid distance = 3.6871 (9) A]. PMID- 22058760 TI - 2-De-oxy-alpha-d-arabino-hexopyran-ose. AB - The title compound, C(6)H(12)O(5), is the alpha-pyran-ose form of the reducing aldose 2-de-oxy-d-arabino-hexose. The six-membered pyran-ose ring adopts a (4)C(1) conformation, with the anomeric hy-droxy group in axial and the other substituents in equatorial positions. In the crystal, each of the four hy-droxy groups acts as an inter-molecular hydrogen-bond donor function, resulting in a three-dimensional hydrogen-bonded network. PMID- 22058761 TI - 7-Amino-4-hy-droxy-4-trifluoro-methyl-3,4-dihydro-quinolin-2(1H)-one. AB - The title compound, C(10)H(9)F(3)N(2)O(2), was prepared by the reaction of m phenyl-enediamine and ethyl 4,4,4-trifluoro-acetoacetate. In the crystal, inter molecular C-H? F, N-H?F, O-H?N and N-H?O inter-actions contribute to the crystal packing. PMID- 22058762 TI - 1-{(1Z)-1-[6-(4-Chloro-phen-oxy)hex-y-l-oxy]-1-(2,4-difluoro-phen-yl)prop-1-en-2 yl}-1H-1,2,4-triazol-4-ium nitrate. AB - In the title compound, C(23)H(25)ClF(2)N(3)O(2) (+).NO(3) (-), the triazole ring makes dihedral angles of 60.9 (4) and 25.0 (3) degrees with the 6-chloro-phenyl and 2,4-difluoro-phenyl rings, respectively. The mol-ecule adopts a Z configuration about the C=C double bond. In the crystal, the cations and anions are linked by N-H?O hydrogen bonds and weak C-H?O inter-actions. PMID- 22058763 TI - 2,4-Dibromo-6-tert-butyl-benzene-1,3-diol. AB - In the title compound, C(10)H(12)Br(2)O(2), a multiply substituted bromo-arene, the C-C-C angles within the aromatic ring are in the range 115.7 (7)-122.4 (7) degrees . In the crystal, mol-ecules are linked by O-H?O hydrogen bonds, but no pi-pi stacking is observed. PMID- 22058764 TI - (4,6-Diamino-1,3-phenyl-ene)bis-(phenyl-methanone). AB - In the mol-ecule of the title compound, C(20)H(16)N(2)O(2), two intra-molecular N H?O inter-actions occur. The mol-ecular chains are linked by N-H?pi and C-H?pi inter-actions into a three-dimensional network, which seems to be very effective in the stabilization of the crystal structure. PMID- 22058765 TI - 1-(2-Amino-eth-yl)-3-phenyl-thio-urea. AB - In the crystal structure of the title compound, C(9)H(13)N(3)S, mol-ecules are linked through N-H?S and N-H?N hydrogen bonds, forming hydrogen-bonded tapes along the b axis. The dihedral angle between the phenyl ring and the thiourea group is 44.9 (2) degrees . PMID- 22058766 TI - Ethyl 1-(4-methyl-phen-yl)-5-phenyl-4-phenyl-sulfon-yl-1H-pyrazole-3-carboxyl ate. AB - The title compound, C(25)H(22)N(2)O(4)S, features a tetra-substituted pyrazole ring. The dihedral angles formed between the five-membered ring (r.m.s. deviation = 0.007 A) and the N- and C-bound phenyl rings are 48.10 (7) and 72.01 (7) degrees , respectively, indicating that the planes through the residues are significantly twisted from the plane through the heterocycle. The ester-CO(2) group is also twisted out of this plane, with an O-C-C-N torsion angle of -29.04 (11) degrees . The sulfonyl-O atoms lie to one side of the pyrazole plane and the sulfonyl-phenyl ring to the other. The dihedral angle between the two ring planes is 70.63 (7) degrees . Supra-molecular arrays are formed in the crystal structure sustained by C-H?O and C-H?pi(pyrazole) inter-actions and methyl-C H?pi(N-bound benzene) contacts. PMID- 22058767 TI - Bis(guanidinium) chloranilate. AB - The asymmetric unit of the title co-crystal, 2CH(6)N(3) (+).C(6)Cl(2)O(4) (2-), contains one half of a chloranilate anion and one guanidinium cation, which are connected by strong N-H?O hydrogen bonds into a two-dimensional network. PMID- 22058768 TI - 1-(3-Chloro-phen-yl)-2-methyl-4-nitro-1H-imidazole-5-carboxamide. AB - In the crystal structure of the title compound, C(11)H(9)ClN(4)O(3), pairs of N H?N(imidazole) hydrogen bonds connect the mol-ecules into centrosymmetric dimers, which are further connected by N-H?O(carbamo-yl) hydrogen bonds into C(4) chains along [010]. Inter-play of these two kinds of hydrogen bonds connect the mol ecules into layers perpendicular to [101]. The imidazole [maximum deviation 0.0069 (9) A] and phenyl rings are inclined at a dihedral angle of 58.44 (6) degrees ; the nitro group is almost coplanar [dihedral angle 5.8 (2) degrees ] with the imidazole ring while the carbamoyl group is almost perpendicular [70.15 (13) degrees ] to it. PMID- 22058769 TI - 2-(Tritylsulfan-yl)ethyl 3-iodo-benzoate. AB - The triphenyl-methyl group in the title compound, C(28)H(23)IO(2)S, has the methine carbon slightly flattened out [SigmaC(phen-yl)-C-C(phen-yl) = 332.8 (6) degrees ]. The -C-O-C-C-S- chain connecting the triphenyl-methyl group and the aromatic ring adopts an extended zigzag conformation, these five atoms being approximately co-planar (r.m.s. deviation 0.260 A). PMID- 22058770 TI - 1-{3-[1-(Hydroxyimino)ethyl]-4-methyl-1H-pyrazol-5-yl}ethanone. AB - In the title compound, C(8)H(11)N(3)O(2), the oxime and the acetyl groups adopt a transoid conformation, while the pyrazole H atom is localized in the proximity of the acetyl group and is cis with respect to the acetyl O atom. In the crystal, dimers are formed as the result of hydrogen-bonding inter-actions involving the pyrazole NH group of one mol-ecule and the carbonyl O atom of another. The dimers are associated into sheets via O-H?N hydrogen bonds involving the oxime hydroxyl and the unprotonated pyrazole N atom, generating a macrocyclic motif with six mol ecules. PMID- 22058771 TI - 1-Bromo-4-methyl-2-nitro-benzene. AB - In the title compound, C(7)H(6)BrNO(2), the dihedral angle between the nitro group and the phenyl ring is 14.9 (11) degrees . PMID- 22058772 TI - tert-Butyl N-(4-hy-droxy-benz-yl)-N-[4-(prop-2-yn-yloxy)benz-yl]carbamate. AB - In the crystal structure of the title compound, C(22)H(25)NO(4), inter-molecular O-H?O hydrogen bonds involving the hy-droxy group of the 4-(amimometh-yl)phenol fragment and the C=O group connect the mol-ecules into infinite chains along the c axis. Two C atoms of the propyne group are disordered over two sites with occupancy factors of 0.53 (2) and 0.47 (2). PMID- 22058773 TI - N,N,N',N'-Tetra-ethyl-N''-(2-fluoro-benzo-yl)phospho-ric triamide. AB - In the title compound, C(15)H(25)FN(3)O(2)P, the phosphoryl group is in an anti and syn orientation to the C=O and N-H groups, respectively. The P atom is in a distorted tetra-hedral environment. One of the ethyl groups is disordered over two sets of sites with refined occupancies of 0.755 (6) and 0.245 (6). In addition, the F atom was refined as disordered with occupancies fixed at 0.9 and 0.1. This disorder corresponds to a rotation of approximately 180 degrees of the fluoro-benzene ring about its connecting C-C bond. In the crystal, pairs of inter molecular N-H?O(=P) hydrogen bonds form centrosymmetric dimers. PMID- 22058774 TI - 4-Chloro-N-(2,4-dimethyl-phen-yl)-2-methyl-benzene-sulfonamide. AB - In the title compound, C(15)H(16)ClNO(2)S, the C-SO(2)-NH-C torsion angle is 67.45 (17) degrees . The two aromatic rings are tilted relative to each other by 44.5 (1) degrees . The crystal structure features inversion-related dimers linked by pairs of N-H?O hydrogen bonds.. PMID- 22058775 TI - 3-(4-Bromo-phen-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde. AB - In the title compound, C(16)H(11)BrN(2)O, the phenyl and chloro-benzene rings are twisted out of the mean plane of the pyrazole ring, forming dihedral angles of 13.70 (10) and 36.48 (10) degrees , respectively. The carbaldehyde group is also twisted out of the pyrazole plane [the C-C-C-O torsion angle is 7.9 (3) degrees ]. A helical supra-molecular chain along the b axis and mediated by C-H?O inter actions is the most prominent feature of the crystal packing. PMID- 22058776 TI - 2-Ethyl-piperidinium chloride. AB - In the title molecular salt, C(7)H(16)N(+).Cl(-), the piperidinium ring adopts a chair conformation. In the crystal, the two components are connected by N-H?Cl and C-H?Cl hydrogen bonds, forming a supra-molecular double-chain structure along the c axis. PMID- 22058777 TI - 2-Azido-1-(3,6-dichloro-9H-fluoren-1-yl)ethanone. AB - In the title compound, C(15)H(9)Cl(2)N(3)O, an intra-molecular C-H?O inter-action generates an S(7) ring motif. The cyclo-penta-1,3-diene ring forms dihedral angles of 1.93 (6) and 2.78 (6) degrees with its attached benzene rings. In the crystal, mol-ecules are linked by C-H?N and C-H?O hydrogen bonds, thereby forming layers lying parallel to the ac plane. The crystal also features a pi-pi inter action with a centroid-centroid distance of 3.5612 (6) A. PMID- 22058778 TI - 2-Methyl-3-{2-nitro-1-[2-(prop-2-yn-1-yl-oxy)phen-yl]eth-yl}-1H-indole. AB - In the title compound, C(20)H(18)N(2)O(3), the indole unit is essentially planar, with a maximum deviation of 0.0197 (18) A for the N atom and forms a dihedral angle of 78.09 (9) degrees with the propyne-subsituted phenyl ring. The propyne group is almost linear, the C-C C angle being 176.5 (2) degrees , and is also in the flagpole position on the O atom. In the crystal, mol-ecules are linked via N H?O and C-H?O inter-molecular hydrogen bonds involving the nitro-group O atoms as acceptors. PMID- 22058779 TI - (7R,8S,9S,12S)-1-Benz-yloxy-13,14-didehydro-12-hy-droxy-2,13-dimeth-oxy-N-methyl morphinane. AB - In the title compound, C(26)H(31)NO(4), a sinomenine derivative, the angle between the two aromatic rings is 53.34 (4) degrees . The N-containing ring is in a chair conformation, while the other two non-planar rings are in a half-boat conformation. In the crystal, mol-ecules are linked by O-H?N inter-actions into a C(8) chain along [100]. PMID- 22058780 TI - 1-(6,8-Dibromo-2-methyl-quinolin-3-yl)ethanone. AB - Two independent mol-ecules,1 and 2, with similar conformations comprise the asymmetric unit in the title compound, C(12)H(9)Br(2)NO. The major difference between the mol-ecules relates to the relative orientation of the ketone-methyl groups [the C-C-C-C torsion angles are -1.7 (6) and -16.8 (6) degrees for mol ecules 1 and 2, respectively]; in each case, the ketone O atom is directed towards the ring-bound methyl group. The crystal packing comprises layers of mol ecules, sustained by C-H?O and pi-pi {ring centroid(C(6)) of molecule 2 with NC(5) of molecule 1 [3.584 (3) A] and NC(5) of molecule 2 [3.615 (3) A]} interactions. C-H?Br contacts also occur. PMID- 22058781 TI - (2E)-1-(5-Chloro-thio-phen-2-yl)-3-(2,3-dimeth-oxy-phen-yl)prop-2-en-1-one. AB - In the title compound, C(15)H(13)ClO(3)S, the chloro-thio-phene and dimeth-oxy phenyl groups are linked by a prop-2-en-1-one group. The C=C double bond exhibits an E conformation. The mol-ecule is non-planar, with a dihedral angle of 31.12 (5) degrees between the chloro-thio-phene and dimeth-oxy-phenyl rings. The meth oxy group at position 3 is coplanar with the benzene ring to which it is attached, with a C-O-C-C torsion angle of -3.8 (3) degrees . The meth-oxy group attached at position 2 of the benzene ring is in a (+)synclinal conformation, as indicated by the C-O-C-C torsion angle of -73.6 (2) degrees . In the crystal, two different C-H?O inter-molecular inter-actions generate chains of mol-ecules extending along the b axis. PMID- 22058782 TI - 4-[2-(4-Chloro-phen-yl)hydrazinyl-idene]-3-methyl-1H-pyrazol-5(4H)-one. AB - In the title compound, C(10)H(9)ClN(4)O, the pyrazole ring [maximum deviation = 0.014 (2) A] forms a dihedral angle of 7.06 (14) degrees with the chloro-benzene ring. The mol-ecular conformation is stabilized by an intra-molecular N-H?O hydrogen bond, which generates an S(6) ring motif. In the crystal, inversion dimers linked by pairs of C-H?O hydrogen bonds generate R(2) (2)(16) ring motifs. The dimers are further connected by N-H?N hydrogen bonds, thereby forming layers lying parallel to the bc plane. PMID- 22058783 TI - rac-3,9-Bis(3-chloro-phen-yl)-2,4,8,10-tetra-oxaspiro-[5.5]undeca-ne. AB - In the title compound, C(19)H(18)Cl(2)O(4), the two non-planar six-membered heterocycles passing through the spiro-C atom both adopt chair conformations, and the dihedral angle between the two benzene rings is 7.2 (1) degrees . In the crystal, the enanti-omers with R and S configurations are generated by the symmetry elements of the centrosymmetric space group, forming a racemic crystal. Inter-molecular C-H?pi and weak C-H?O inter-actions link the mol-ecules in the crystal structure. PMID- 22058784 TI - 1-(1-Benzofuran-2-yl)-2-(phenyl-sulfon-yl)ethanone. AB - The overall mol-ecular conformation of the title compound, C(16)H(12)O(4)S, is elongated, the dihedral angle formed between the benzofuran (r.m.s. deviation = 0.018 A) and benzene rings being 24.81 (6) degrees . Both sulfonyl O atoms lie to one side of the S-bound benzene ring, and the carbonyl and furan O atoms are syn to each other. Supra-molecular arrays parallel to (101) sustained by C-H?O contacts feature in the crystal packing. PMID- 22058785 TI - 1,3-Dicyclo-hexyl-3-[(pyridin-2-yl)carbon-yl]urea monohydrate from synchrotron radiation. AB - The title urea derivative crystallizes as a monohydrate, C(19)H(27)N(3)O(2).H(2)O. The central C(3)N grouping is almost planar (r.m.s. deviation = 0.0092 A), and the amide and pyridine groups are substanti-ally twisted out this plane [dihedral angles = 62.80 (12) and 34.98 (10) degrees , respectively]. Supra-molecular double chains propagating along the b-axis direction feature in the crystal packing whereby linear chains sustained by N-H?O hydrogen bonds formed between the amide groups are linked by helical chains of water mol-ecules (linked by O-H?O hydrogen bonds). The H atom that participates in these water chains is disordered over two positions of equal occupancy. The double chains are connected into a two-dimensional array by C-H?O contacts and the layers stack along the a axis. PMID- 22058786 TI - N-Diphenyl-phosphanyl-N-{[diphen-yl(2-pyridyl-imino)-lambda-phosphan-yl]meth yl}pyridin-2-amine. AB - In the title compound, C(35)H(30)N(4)P(2), the diphenyl-phosphanyl and diphen yl(2-pyridyl-imino)-lambda(5)-phosphanyl groups are attached to the central methyl C atom with a P-C-N angle of 114.09 (16) degrees . The mol-ecules stack along the b axis and inter-connect through C-H(pyrid-yl)?N(pyrid-yl) inter actions, forming an infinite chain structure. The parallel chains are further inter-connected via C-H(benzene)?N(amino) and C-H(benzene)?pi inter-actions, forming a three-dimensional framework. PMID- 22058787 TI - 7-Amino-heptyl-aza-nium iodide. AB - The absolute structure of the title compound, [H(3)N-(CH(2))(7)-NH(2)]I, has been determined from the diffraction experiment, the Flack parameter refining to -0.02 (2). In the crystal, adjacent symmetry-related cations are connected by head-to tail R'H(2)N(+)-H?NH(2)R hydrogen bonds, forming chains along [010]. The remaining four H atoms attached to the amino and the aza-nium group form weak hydrogen bonds to neighbouring iodide anions, producing a three-dimensional hydrogen-bonded network. The amino group and the aliphatic chain of the 7-amino heptyl-aza-nium cation show an exact all-trans conformation, within experimental uncertainties. The aza-nium group, to fulfill the needs of hydrogen bonding, is twisted out of the plane defined by the C atoms of the aliphatic chain, the C-C-C N torsion angle being -65.4 (4) degrees . PMID- 22058788 TI - (E)-2-(3-Cinnamoyl-thio-ureido)acetic acid dimethyl sulfoxide disolvate. AB - In the title compound, C(12)H(12)N(2)O(3)S.2C(2)H(6)OS, the acetic acid and cinnamoyl groups adopt Z and E configurations, respectively, with respect to the thio group about the C-N bonds. The components of the asymmetric unit are connected by N-H?O and O-H?O hydrogen bonds and in the crystal weak inter molecular C-H?O and C-H?S hydrogen bonds further connect the components into chains along the b axis. In the main mol-ecule, an intra-molecular N-H?O hydrogen bond is also present. PMID- 22058789 TI - (E)-2-[1-(1-Benzothio-phen-2-yl)ethyl-idene]-N-phenyl-hydrazinecarboxamide. AB - The title compound, C(17)H(15)N(3)OS, crystallizes with two unique mol-ecules, denoted 1 and 2, in the asymmetric unit. The two mol-ecules are closely similar and overlay with an r.m.s. deviation of 0.053 A. Both mol-ecules adopt E configurations with respect to the C=N bonds. The dihedral angles between the benzothio-phene groups and N-bound phenyl rings are 36.36 (9) degrees for mol ecule 1 and 29.71 (9) degrees for mol-ecule 2. The C=N-NH-C(O)NH ethyl-idene hydrazinecarboxamide units are also reasonably planar, with r.m.s. deviations of 0.061 and 0.056 A, respectively, for the two mol-ecules. The methyl substituents lie 0.338 (3) and 0.396 (3) A, respectively, from these planes. The C=N-NH-C(O)NH planes are inclined to the phenyl rings at 13.65 (11) and 15.56 (11) degrees , respectively, in mol-ecules 1 and 2. This conformation is enhanced by weak intra molecular C-H?O hydrogen bonds between ortho-H atoms of the two phenyl rings and the carbonyl O atoms, which generate S(6) rings in each mol-ecule. In the crystal, pairs of mol-ecules are linked by pairs of inter-molecular N-H?O hydrogen bonds into dimers. Alternating dimers are further inter-connected by weak C-H?O contacts into zigzag rows along b. The rows are stacked along a by C H?pi contacts involving the benzene ring from molecule 2 and the thiophene ring from molecule 1 of adjacent benzothio-phene units. PMID- 22058790 TI - [(4-Dimethyl-amino-2-methyl-5-phenyl-furan-3-yl)meth-yl]diethyl-methyl-aza-nium iodide. AB - In the title compound, C(19)H(29)N(2)O(+).I(-), the dihedral angle between the mean planes of the essentially planar furan (r.m.s. deviation = 0.007 A) and phenyl rings is 48.4 (1) degrees . In the crystal, cations and anions are arranged in layers lying parallel to (100). PMID- 22058791 TI - 2-(4-Hy-droxy-phen-yl)-3-(trimethyl-sil-yl)propanaminium chloride. AB - In the title crystal structure, C(12)H(22)NOSi(+).Cl(-), anions and cations are linked via O-H?Cl, N-H?Cl and N-H?O hydrogen bonds to form a two-dimensional network parallel to (101). Within the hydrogen-bonded network, R(4) (2)(22) ring motifs are stacked along [010]. PMID- 22058792 TI - 3,6-Dibromo-naphthalene-2,7-diyl bis-(trifluoro-methane-sulfonate). AB - The naphthalene fused ring of the title compound, C(12)H(4)Br(2)F(6)O(6)S(2), is slightly buckled (r.m.s. deviation = 0.036 A) along the common C-C bond and the benzene rings are twisted by 3.2 (3) degrees . The two trifluoro-methyl-sulfonyl groups lie on opposite sides of the fused-ring system. The crystal structure features short inter-molecular F?F contacts [2.715 (4) and 2.832 (4) A]. PMID- 22058793 TI - 2-{(1S,2S,4aR,8R,8aR)-8-Hy-droxy-4a,8-dimethyl-1-[(2E)-2-methyl-but-2-eno-yl oxy]perhydro-naphthalen-2-yl}acrylic acid from Sclerorhachis platyrachis. AB - The eudesmane-type terpenoid, C(20)H(30)O(5), isolated from Sclerorhachis platyrachis, has a deca-lin skeleton whose six-membered rings adopt chair conformations. The two methyl substituents occupy axial positions, whereas the other three substituents occupy equatorial positions. The hy-droxy group is an intra-molecular hydrogen-bond donor to the single-bond ester O atom; adjacent mol ecules are linked through the carb-oxy-lic acid interacting with the hydroxyl group, forming a hydrogen-bonded chain running along the c axis. PMID- 22058794 TI - Ethyl 1-(2-hy-droxy-eth-yl)-2-propyl-1H-benzimidazole-5-carboxyl-ate. AB - In the title compound, C(15)H(20)N(2)O(3), the benzimidazole ring is essentially planar, with a maximum deviation from the mean plane of 0.012 (1) A. The crystal structure is stabilized by inter-molecular O-H?N hydrogen bonds, forming centrosymmetric dimers, which are connected in the [100] direction through weak C H?O contacts. PMID- 22058795 TI - 1,4-Bis(1,1-dimethyl-prop-yl)-2,5-dimeth-oxy-benzene. AB - The title compound, C(18)H(30)O(2), was prepared by Friedel-Crafts alkyl-ation of 1,4-dimeth-oxy-benzene with 2-methyl-2-butanol. The complete mol-ecule is generated by the application of a crystallographic centre of inversion. The two meth-oxy groups are oriented in the same plane of the aromatic ring [C-C-O-C torsion angle = 9.14 (16) degrees ]. While one methyl group of the tert-pentyl substituent is coplanar with the benzene ring [C-C-C-C = 0.45 (15) degrees ] and lies towards the less-hindered H atom, the other methyl and ethyl groups are directed to either side of the benzene ring [C-C-C-C torsion angles = 118.78 (12) and 59.11 (14) degrees , respectively]. In the crystal, the hydro-phobic mol ecules pack to form a brick-wall-like architecture. PMID- 22058796 TI - 1-Diphenyl-methyl-4-[3-(4-fluoro-benzo-yl)prop-yl]piperazine-1,4-diium dichloride monohydrate. AB - In the title compound, C(27)H(31)FN(2)O(2+).2Cl(-).H(2)O, the piperazine ring adopts a chair conformation and both N atoms are protonated. The Cl(-) anions form strong hydrogen bonds to these protons. O/N-H?Cl and C-H?O hydrogen bonds link the anions, cations and water of hydration into a three-dimensional network. PMID- 22058797 TI - rac-3-{4-[(2-Hy-droxy-benzyl-idene)amino]-3-phenyl-5-sulfanyl-idene-4,5-dihydro 1H-1,2,4-triazol-1-yl}-1,3-diphenyl-propan-1-one. AB - In the title compound, C(30)H(24)N(4)O(2)S, the four phenyl rings of the substituent groups make dihedral angles of 88.1 (2), 81.0 (2), 21.4 (2) and 44.6 (2) degrees with the triazole group. An intra-molecular hy-droxy-imino O-H?N hydrogen bond results in the formation of an approximately planar (r.m.s deviation = 0.0230 A) six-membered ring. PMID- 22058798 TI - rac-3-{4-[(4-Nitro-benzyl-idene)amino]-3-phenyl-5-sulfanyl-idene-4,5-dihydro-1H 1,2,4-triazol-1-yl}-1,3-diphenyl-propan-1-one. AB - In the title mol-ecule, C(30)H(23)N(5)O(3)S, the 1,2,4-triazole ring is approximately planar (r.m.s. deviation = 0.006 A), and forms dihedral angles of 66.0 (2), 65.1 (2), 30.1 (2) and 28.1 (2) degrees with the four phenyl rings. The phenyl ring of the benzyl group directly attached to the triazole ring is almost perpendicular to the nitro-phenyl ring, making a dihedral angle of 84.9 (2) degrees . PMID- 22058799 TI - Bis(2,4,6-trimethyl-anilinium) sulfate monohydrate. AB - In the crystal structure of the title compound, 2C(9)H(14)N(+).SO(4) (2-).H(2)O, the components are linked by inter-molecular N-H?O and O-H?O hydrogen bonds. N H?S and O-H?S inter-actions also occur. PMID- 22058800 TI - 3-(3-Chloro-2-hy-droxy-phen-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde. AB - In the title compound, C(16)H(11)ClN(2)O(2), the pyrazole ring makes dihedral angles of 11.88 (13) and 22.33 (13) degrees with the 3-chloro-2-hy-droxy-benzene group and phenyl rings, respectively. The phenolic hy-droxy group forms an intra molecular O-H?N hydrogen bond with the imine N atom of the pyrazole unit. The formyl group is virtually coplanar with the pyrazole ring [dihedral angle = 4.5 (19) degrees ] and acts as an acceptor in an intra-molecular C-H?O hydrogen bond closing seven-membered ring. In the crystal, adjacent mol-ecules are linked through C-H?O hydrogen bonds into infinite chains along the b axis. PMID- 22058801 TI - (Z)-Methyl 3-(2,4-dichloro-phen-yl)-2-[(2-formyl-phen-oxy)meth-yl]acrylate. AB - In the title compound, C(18)H(14)Cl(2)O(4), the mean planes of the methyl acrylate unit and the phenyl ring of the benzaldehyde are approximately orthogonal to each other, making a dihedral angle of 83.31 (6) degrees . The O atom of the aldehyde group is displaced significantly from the phenyl ring plane by 0.226 (2) A. The methyl acrylate group adopts an E conformation. In the crystal, inversion dimers linked by pairs of C-H?O hydrogen bonds generate R(2) (2)(24) loops. PMID- 22058802 TI - 4-[2-(4-Chloro-phen-yl)hydrazinyl-idene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1 carbothio-amide. AB - In the title mol-ecule, C(11)H(10)ClN(5)OS, an intra-molecular N-H?O hydrogen forms an S(6) ring motif. The dihedral angle between the pyrazole ring and the benzene ring is 3.77 (8) degrees . In the crystal, mol-ecules are linked by N-H?S and N-H?O hydrogen bonds into layers parallel to the bc plane. PMID- 22058803 TI - 4-[Bis(3-phenyl-1H-pyrazol-1-yl)meth-yl]benzene-1,2-diol. AB - The title compound, C(25)H(20)N(4)O(2), is a ditopic ortho-hydro-quinone-based bis-(pyrazol-1-yl)methane ligand. The dihedral angles between the planes of the pyrazole rings and their attached phenyl rings are 17.4 (3) and 5.9 (4) degrees . The pyrazole rings make a dihedral angle of 87.84 (16) degrees . One of the two hy-droxy groups forms an intra-molecular hydrogen bond to the other hy-droxy group, whereas the second is involved in an inter-molecular O-H?N hydrogen bond. As a result of these inter-molecular hydrogen bonds, helical chains running along the b axis are formed. PMID- 22058804 TI - 2-(5-Bromo-pyridin-3-yl)-5-[3-(4,5,6,7-tetra-hydro-thieno[3,2-c]pyridine-5 ylsulfon-yl)thio-phen-2-yl]-1,3,4-oxa-diazole. AB - In the title compound, C(18)H(13)BrN(4)O(3)S(3), the tetra-hydro-pyridine ring adopts a half-chair conformation with the central methyl-ene-C atom of the NCH(2)CH(2) unit at the flap. The dihedral angles between the tetra-hydro pyridine ring and the pyridine and two thio-phene rings are 69.34 (13) 5.66 (13) and 68.63 (13) degrees , respectively, while the dihedral angle between the 1,3,4 oxadiazole and tetra-hydro-pyridine rings is 54.76 (13) degrees . The mol-ecule is stabilized by an intra-molecular C-H?N inter-action. In the crystal, adjacent mol-ecules are connected via bifurcated C-H?(N,O) hydrogen bonds, forming a chain along the b axis. PMID- 22058805 TI - 3-Amino-1-(4-bromo-phen-yl)-9,10-dihydro-phenanthrene-2,4-dicarbonitrile. AB - In the title compound, C(22)H(14)BrN(3), the fused-ring system is buckled owing to the ethyl-ene linkage in the central ring; the two flanking aromatic rings are twisted by 25.9 (1) degrees with respect to each other. The phenyl ring is twisted by 77.0 (1) degrees relative to the amino- and cyano-bearing aromatic ring. In the crystal, adjacent mol-ecules are linked by two N-H?N hydrogen bonds, generating a zigzag chain along [101]. PMID- 22058806 TI - 2-Ethyl-imidazolium terephthalate. AB - The asymmetric unit of the title compound, C(5)H(9)N(2) (+).C(8)H(5)O(4) (-), consists of one protonated 2-ethyl-imidazolium cation and two half terephthalate anions. The anions and cations are linked through N-H?O hydrogen bonds while the anions are associated via O-H?O inter-actions, resulting in a layered structure. The ethyl group of the cation is disordered over twosites of occupancies 0.812 (14) and 0.188 (14). The hydroxy H atoms of the anions are equally disordered over two symmetry-related sites. PMID- 22058807 TI - 1,1-Dimethyl-hydrazin-1-ium picrate. AB - In the title compound, C(2)H(9)N(2) (+).C(6)H(2)N(3)O(7) (-), the dihedral angles between the mean planes of the three nitro groups and the benzene ring are 63.5 (3), 10.5 (2) and 10.4 (2) degrees . In the crystal, mol-ecules are linked by N H?O hydrogen bonds into a two-dimensional network parallel to (001). PMID- 22058808 TI - Methyl N-(4-chloro-phen-yl)carbamate. AB - In the title compound, C(8)H(8)ClNO(2), the dihedral angle between the chloro benzene ring and the side chain is 8.79 (11) degrees . In the crystal, mol-ecules are linked by N-H?O hydrogen bonds into a C(4) chain propagating in the b-axis direction. PMID- 22058809 TI - 4a-Hydroxy-9-(4-hydroxyphenyl)-4,4a,5,6,9,9a-hexahydro-3H-xanthene-1,8(2H,7H) dione. AB - The title compound, C(19)H(20)O(5), was synthesized by the reaction of 1,3-cyclo hexa-nedione and 4-hy-droxy-benzaldehyde in the presence of PdCl(2) and thio urea. The tetra-hydro-pyran ring and the six-membered cyclo-hexene ring adopt envelope conformations, and the six-membered cyclo-hexane ring is in a chair conformation. The crystal packing is stabilized by classical inter-molecular O H?O hydrogen bonds and weak C-H?O inter-actions. PMID- 22058810 TI - 11alpha,15alpha-Dihy-droxy-androst-4-ene-3,17-dione. AB - The title compound, C(19)H(26)O(4), was biotransformed from androstenedione. In the crystal, inter-molecular O-H?O hydrogen bonds link molecules into a corrugated sheet, which lies parallel to the ab plane. Ring A has a slightly distorted half-chair conformation, rings B and C adopt chair conformations, while the cyclo-pentane ring D adopts a 14alpha-envelope conformation. PMID- 22058811 TI - (E)-Methyl 3-(4-ethyl-phen-yl)-2-{2-[(E)-(hy-droxy-imino)-meth-yl]phen-oxy-meth yl}acrylate. AB - In the title compound, C(20)H(21)NO(4), the two benzene rings are almost perpendicular to each other, making a dihedral angle of 86.1 (7) degrees . The hy droxy-ethanimine group is essentially coplanar with the benzene ring, the largest deviation from the mean plane of the hy-droxy-ethanimine [C=N-OH] group being 0.011 (1) A for the O atom. An intra-molecular C-H?O hydrogen bond occurs. The mol-ecules are linked into cyclic centrosymmetric R(2) (2)(6) dimers via O-H?N hydrogen bonds. Inter-molecular C-H?O hydrogen bonds link the mol-ecules, forming a C(8) chain along the a axis. The crystal packing is further stabilized by C H?pi inter-actions. PMID- 22058812 TI - 2-{(1E)-1-[(3-{(E)-[1-(2-Hy-droxy-4-meth-oxy-phen-yl)ethyl-idene]amino}-2,2-di methyl-prop-yl)imino]-eth-yl}-5-meth-oxy-phenol. AB - Mol-ecules of the title compound, C(23)H(30)N(2)O(4), are located on a crystallographic mirror plane. The mol-ecule has a curved shape with the dihedral angle formed between the two benzene rings being 55.26 (5) degrees . Intra molecular O-H?N hydrogen bonds are noted. In the crystal, supra-molecular layers are formed in the ac plane owing to the presence of C-H?pi inter-actions. PMID- 22058813 TI - 2,4-Diamino-6-methyl-1,3,5-triazin-1-ium tetra-fluoro-borate. AB - In the crystal structure of the title salt, C(4)H(8)N(5) (+).BF(4) (-), centrosymmetrically related cations undergo base pairing via a pair of N-H?N hydrogen bonds, forming an R(2) (2)(8) ring motif. The cations and anions inter act via N-H?F hydrogen bonds, generating supra-molecular layers parallel to ([Formula: see text]20), which are in turn linked into a three-dimensional network, forming rings of R(6) (6)(24) graph-set motif. The crystal structure is further stabilized by pi-pi stacking inter-actions [centroid-centroid distance = 3.3361 (12) A]. PMID- 22058814 TI - (S)-5-Oxo-N-phenyl-pyrrolidine-2-carboxamide. AB - The title compound, C(11)H(12)N(2)O(2), shows an S configuration, in which the pyrrolidinone ring is twisted with respect to the phenyl plane, making a dihedral angle of 70.73 (7) degrees . In the crystal, mol-ecules are linked by N-H?O hydrogen bonds, building up a layer parallel to (001). PMID- 22058815 TI - Ethyl 5-hy-droxy-6-oxo-4-phenyl-5,6-dihydro-4H-cyclo-penta-[b]thio-phene-5 carboxyl-ate. AB - In the title mol-ecule, C(16)H(14)O(4)S, the dihydro-cyclo-penta-thio-phenone ring system is almost planar, with an r.m.s. deviation of 0.060 A from the best fit plane through all nine non-H atoms. The cyclo-penta-none ring adopts a severely flattened envelope conformation with the C atom carrying the OH and ethylcarboxylate substituents at the flap. This atom lies only 0.185 (3) A from the plane through the other four C atoms. The phenyl substituent is inclined at 43.37 (5) degrees to the dihydro-cyclo-penta-thio-phenone mean plane. In the crystal, mol-ecules are linked by pairs of O-H?O hydrogen bonds, forming inversion dimers with R(2) (2)(10) ring motifs. Weak C-H?O hydrogen bonds also link mol-ecules into chains along c, while an approximately orthogonal set of C H?O contacts form chains along b, resulting in layers lying parallel to (100). Inversion dimers also form through weaker R(2) (2)(12) C-H?S contacts, which combine with C-H?O contacts to form stacks along b. PMID- 22058816 TI - 9-Hy-droxy-4,8-dimethyl-12-(piperidin-1-ylmeth-yl)-3,14-dioxatricyclo [9.3.0.0]tetra-dec-7-en-13-one. AB - The title compound, C(20)H(31)NO(4), was synthesized from 9alpha-hy-droxy parthenolide (9alpha-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo [9.3.0.0(2,4)]tetra-dec-7-en-13-one), which was isolated from the chloro-form extract of the aerial parts of Anvillea radiata. The mol-ecule is built up from fused five-and ten-membered rings with the pipyridin-1-yl-methyl group as a substituent. The ten-membered ring adopts an approximate chair-chair conformation, while the six-membered ring display a chair conformation and the five-membered ring an envelope conformation with the C(H)-C-C(H) atom at the flap. The dihedral angle between the ten-membered ring and the lactone ring is 21.7 (4) degrees . The mol-ecular conformation is stabilized by an O-H?N hydrogen bond and the crystal structure is stabilized by weak inter-molecular C-H?O inter actions. PMID- 22058817 TI - Moxifloxacinium chloride monohydrate. AB - The title compound {systematic name: 7-[(1S,6S)-8-aza-2-azonia-bicyclo-[4.3.0]non 8-yl]-1-cyclo-propyl-6-fluoro-8-meth-oxy-4-oxo-1,4-dihydro-quinoline-3-carb-oxy lic acid chloride monohydrate}, C(21)H(25)FN(3)O(4) (+).Cl(-).H(2)O, crystallizes with two moxi-floxa-cinium cations, two chloride ions and two uncoordinated water mol-ecules in the unit cell. The crystal structure has a pseudo-inversion center except for the chloride ions. In both moxi-floxa-cinium cations, the quinoline rings are approximately planar, the maximum atomic deviations being 0.107 (3) and 0.118 (3) A. The piperidine rings adopt a chair conformation while the pyrrolidine rings display a half-chair conformation. In the crystal, the carboxyl groups, the protonated piperidyl groups, the uncoordinated water mol-ecule and chloride anions participate in O-H?O, O-H?Cl and N-H?Cl hydrogen bonding; weak inter-molecular C-H?O and C-H?Cl hydrogen bonding is also present in the crystal structure. PMID- 22058818 TI - 5-O-Acetyl-d-ribono-1,4-lactone. AB - The title compound, C(7)H(10)O(6), was obtained from a regioselective enzyme catalysed acyl-ation of d-ribono-1,4-lactone. The five-membered ring of the acyl ated sugar shows an envelope conformation. In the crystal, the mol-ecules are linked by inter-molecular O-H?O hydrogen-bonds, forming a one-dimensional polymeric structure parallel to [010]. In addition, packing analysis shows stacking along the b axis. PMID- 22058819 TI - N-Cyclo-hexyl-4-[(2-nitro-anilino)-meth-yl]thio-phene-2-sulfonamide. AB - In the title compound, C(17)H(21)N(3)O(4)S(2), an intra-molecular N-H?O hydrogen bond involving the proximate amine and nitro groups is observed. In the crystal, inter-molecular N-H?O hydrogen bonds involving the amine and SO(2) groups occur. One of the notro O atoms is disordered over two conformations with occupancies of 0.578 (12) and 0.422 (12). PMID- 22058820 TI - 2-(Biphenyl-4-yl)-5-[3-(4,5,6,7-tetra-hydro-thieno[3,2-c]pyridine-5-ylsulfon yl)thio-phen-2-yl]-1,3,4-oxa-diazole. AB - In the title mol-ecule, C(25)H(19)N(3)O(3)S(3), the tetra-hydro-pyridine ring adopts a half-chair conformation. The dihedral angle between the least-squares plane through the tetra-hydro-pyridine ring and two thio-phene and two benzene rings are 6.25 (9), 89.49 (9), 76.43 (9) and 84.93 (8) degrees , respectively, while the dihedral angle between the 1,3,4-oxadiazole and tetra-hydro-pyridine rings is 81.14 (9) degrees . In the crystal, adjacent mol-ecules are connected via weak C-H?N hydrogen bonds, forming a chain along the b axis. PMID- 22058821 TI - Monoclinic polymorph of 4-[(1H-benz-imidazol-1-yl)meth-yl]benzoic acid. AB - Three polymorphs of the title compound, C(15)H(12)N(2)O(2), were obtained accidentally as single crystals in the hydro-thermal reaction of the title compound with manganese bromide in the presence of N,N'-dimethyl-formamide at 373 K. Here we report the structure of the first polymorph. The benzimidazole ring is almost planar, the maximum deviation from the mean plane being 0.016 (1) A. The benzimidazole and benzene rings are approximately perpendicular, making a dihedral angle 85.56 (7) degrees , which is a reflection of the axial rotation of the flexible benzimidazolyl arm. In the crystal, adjacent mol-ecules are connected through O-H?N hydrogen bonds into a chain along [100], and neighboring chains are further linked by via weak C-H?O hydrogen-bonding inter-actions, forming a two-dimensional network. PMID- 22058822 TI - 4-Sulfamoylanilinium nitrate. AB - In the crystal structure of the title compound, C(6)H(9)N(2)O(2)S(+).NO(3) (-), the cations and anions are connected by N-H?O hydrogen bonds into a three dimensional network. PMID- 22058823 TI - 4-Amino-pyridinium cis-2-carb-oxy-cyclo-hexane-1-carboxyl-ate. AB - In the structure of the title molecular salt, C(5)H(7)N(2) (+).C(8)H(11)O(4) (-), the cis monoanions associate through short O-H?O hydrogen bonds in the carb-oxy lic acid groups [graph set C(7)], forming zigzag chains which extend along the c axis. These are inter-linked through pyridinium and amine N-H?O hydrogen bonds, giving a three-dimensional network structure. PMID- 22058824 TI - 9-p-Tolyl-9H-carbazole-3-carbonitrile. AB - In the title compound, C(20)H(14)N(2), the carbazole ring system is essentially planar (r.m.s. deviation = 0.187 A) and is inclined at an angle of 54.33 (4) degrees with respect to the benzene ring. The crystal packing is stabilized by weak C-H?N and C-H?pi inter-actions. PMID- 22058825 TI - 7H-1-Benzofuro[2,3-b]carbazole. AB - In the title compound, C(18)H(11)NO, the carbazole and benzofuran rings are almost co-planar, making a dihedral angle of 3.31 (3) degrees . The crystal structure is stabilized by weak C-H?pi inter-actions. PMID- 22058826 TI - 7-Phenyl-7H-dinaphtho-[2,1-b:1',2'-d]phosphole 7-oxide. AB - In the title compound, C(26)H(17)OP, the naphthyl ring systems are bent away from each other [dihedral angle = 30.81 (8) degrees ]. In the crystal, weak inter molecular C-H?O inter-actions link the mol-ecules into helical chains along the 2(1) screw axis. PMID- 22058827 TI - Benzyl 2-{4-[2-(4-chloro-benzoyl-amino)-eth-yl]phen-oxy}-2-methyl-propionate. AB - In the title compound, C(26)H(26)ClNO(4), the central phenyl-ene ring is oriented at dihedral angles of 5.06 (14) and 64.14 (5) degrees , respectively, with respect to aromatic rings of the benzyl and chloro-phenyl groups. The centroid centroid distance between the central phenyl-ene ring and the aromatic ring of the benzyl group is 4.028 (12) A. In the crystal, inter-molecular N-H?O hydrogen bond generate a chain along (100). C-H?O inter-actions are also observed. PMID- 22058828 TI - 3-tert-Butyl-2-oxo-1-oxaspiro-[4.5]dec-3-en-4-yl 4-chloro-benzoate. AB - The title tetronic acid derivative, C(20)H(23)ClO(4), which is a spiro-diclofen analogue, has two crystallographically independent mol-ecules in the asymmetric unit (Z' = 2). The cyclo-hexane rings in the respective mol-ecules A and B adopt chair conformations [four C atoms are planar with mean deviations of 0.013 (2) and 0.001 (2) A, and the flap positions deviate by 0.653 (4) and -0.663 (3) A (mol-ecule A) and 0.642 (4) and -0.643 (5) A (mol-ecule B) from the plane]. The furan ring makes dihedral angles of 86.9 (1) (mol-ecule A) and 85.4 (1) degrees (mol-ecule B) with the respective benzene rings. PMID- 22058829 TI - 5-Chloro-3-cyclo-pentyl-sulfonyl-2-methyl-1-benzofuran. AB - In the title compound, C(14)H(15)ClO(3)S, the cyclo-penyl ring adopts an envelope conformation. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds into dual chains propagating in [100]. The dual chains arise from pairs of the same or different hydrogen bonds between adjacent molecules. PMID- 22058830 TI - Isopropyl 4-nitro-benzoate. AB - In the mol-ecule of the title compound, C(10)H(11)NO(4), the nitro group is approximately coplanar with the benzene ring [dihedral angle = 4.57 (10) degrees ], while the carboxyl-ate group is slightly twisted, making an angle of 12.16 (8) degrees . In the crystal, weak inter-molecular C-H?O hydrogen bonding and pi-pi stacking inter-actions [centroid-centroid distances = 3.670 (2) and 3.665 (2) A] are observed. PMID- 22058831 TI - 7-Chloro-3-phenyl-benzo[4,5]thia-zolo[2,3-c][1,2,4]triazole. AB - In the title compound, C(14)H(8)ClN(3)S, the dihedral angle between the approximately planar triple-fused ring system (r.m.s. deviation = 0.065 A) and the pendant phenyl ring is 62.25 (5) degrees . In the crystal, mol-ecules are linked into infinite chains along the c-axis direction by C-H?N hydrogen bonds. Aromatic pi-pi stacking inter-actions [centroid-centroid distances = 3.7499 (8) and 3.5644 (8) A] and weak C-H?pi inter-actions are also observed. PMID- 22058832 TI - Manganese(II) octa-uranium(IV) hepta-deca-sulfide. AB - Single crystals of manganese(II) octa-uranium(IV) hepta-deca-sulfide, MnU(8)S(17), were grown from the reaction of the elements in a RbCl flux. MnU(8)S(17) crystallizes in the space group C2/m in the CrU(8)S(17) structure type. The asymmetric unit is composed of the following atoms with site symmetries shown: U1 (1), U2 (m), U3 (m), Mn1 (2/m), S1 (1), S2 (1); S3 (m), S4 (m), S5 (m), S6 (m) and S7 (2/m). The three U(IV) atoms are each coordinated by eight S atoms in a bicapped trigonal-prismatic arrangement. The Mn(II) atom is coordinated by six S atoms in a distorted octa-hedral arrangement. PMID- 22058833 TI - (4,5-Diaza-fluoren-9-one-kappaN,N')bis-(1H-imidazole-kappaN)bis-(thio-cyanato kappaN)cobalt(II). AB - In the title complex, [Co(NCS)(2)(C(3)H(4)N(2))(2)(C(11)H(6)N(2)O)], the Co(II) atom has a distorted octa-hedral coordination with the N atoms of the 4,5-diaza fluoren-9-one ligand and two N atoms from imidazole ligands in the equatorial positions and the axial sites occupied by two N atoms of the thio-cyanate ligand. Inter-molecular N-H?O hydrogen bonding forms a one-dimensional motif parallel to the cell ab diagonal. PMID- 22058834 TI - catena-Poly[[bis-(N,N-dimethyl-formamide-kappaO)zinc]-MU(2)-oxalato kappaO,O:O,O]. AB - In the crystal structure of the title compound, [Zn(C(2)O(4))(C(3)H(7)NO)(2)](n), the Zn(II) ion is situated on a twofold rotation axis and has a distorted octa hedral coordination geometry defined by the O atoms of two dimethyl-formamide mol ecules and four O atoms of two bidentate oxalate ligands. The oxalate anion is located on an inversion centre and bridges two metal ions, resulting in a polymeric structure with infinite zigzag chains extending parallel to [010]. PMID- 22058835 TI - Poly[[{MU(3)-2-[4-(2-hy-droxy-eth-yl)piperazin-1-yl]ethane-sulfonato}-silver(I)] trihydrate]. AB - Ethane-sulfonic acid-based buffers like 2-[4-(2-hy-droxy-eth-yl)-piperazin-1 yl]ethane-sulfonic acid (HEPES) are commonly used in biological experiments because of their ability to act as non-coordinating ligands towards metal ions. However, recent work has shown that some of these buffers may in fact coordinate metal ions. The title complex, {[Ag(C(8)H(17)N(2)O(4)S)].3H(2)O}(n), is a metal organic framework formed from HEPES and a silver(I) ion. In this polymeric complex, each Ag atom is primarily coordinated by two N atoms in a distorted linear geometry. Weaker secondary bonding inter-actions from the hy-droxy and sulfate O atoms of HEPES complete a distorted seesaw geometry. The crystal structure is stabilized by O-H?O hydrogen-bonding interactions. PMID- 22058836 TI - Di-MU-chlorido-bis-{[4-amino-3,5-bis-(2-pyrid-yl)-4H-1,2,4-triazole kappaN]chloridomercury(II)}. AB - In the centrosymmetric binuclear title complex, [Hg(2)Cl(4)(C(12)H(10)N(6))(2)], the Hg(II) ion is five-coordinated by two N atoms and three chloride ions with a distorted square-pyramidal geometry. In the complex, there is an intra-molecular N-H?N hydrogen bond. In the crystal, the binuclear units are connected by inter molecular N-H?Cl hydrogen bonds, as well as pi-pi stacking inter-actions [centroid-centroid distances = 3.526 (2) and 3.696 (2) A], forming a two dimensional layered structure parallel to (010). PMID- 22058837 TI - MU-Acetato-diacetato{MU-6,6'-dimethoxy-2,2'-[o phenylenebis(nitrilomethanylylidene)]diphenolato}gadolinium(III)zinc. AB - In the heterodinuclear title complex, [GdZn(C(22)H(18)N(2)O(4))(CH(3)COO)(3)], the Zn(II) ion is five-coordinated in a square-pyramidal environment defined by two O atoms and two N atoms from the ligand, forming the square plane, and one acetate O atom serving as the apex, while the Gd(III) ion is nine-coordinated in an approximate mono-capped tetra-gonal-anti-prismatic environment defined by four O atoms from the ligand and five acetate O atoms. PMID- 22058838 TI - trans-Diaqua-bis-[5-carb-oxy-2-(3-pyrid-yl)-1H-imidazole-4-carboxyl-ato kappaN,O]cobalt(II). AB - In the title complex, [Co(C(10)H(6)N(3)O(4))(2)(H(2)O)(2)], the Co(II) atom is located on an inversion centre and displays a distorted octa-hedral coordination geometry defined by two N,O-bidentate ligands in the equatorial plane and two water mol-ecules in the axial positions. The conformation is stabilized by intra molecular O-H?O hydrogen bonds. Inter-molecular N-H?O hydrogen bonds link the mol ecules into chains, which are further connected by inter-molecular O-H?O and O H?N hydrogen-bonding inter-actions, forming a two-dimensional supra-molecular network parallel to (110). PMID- 22058839 TI - [6-(4-Bromo-phen-yl)-2,2'-bipyridine-kappaN,N']bis-(triphenyl-phosphane kappaP)copper(I) tetra-fluoridoborate. AB - The title compound, [Cu(C(16)H(11)BrN(2))(C(18)H(15)P)(2)]BF(4), is composed of one Cu(I) atom, one 6-(4-bromo-phen-yl)-2,2'-bipyridine (L) ligand, two triphenyl phosphane mol-ecules and one tetra-fluoridoborate anion. The Cu(I) ion is four coordinated in a distorted tetra-hedral configuration by two N atoms from L and two P atoms from triphenyl-phosphane ligands. In the L ligand, the two pyridine rings are not coplanar; the mean planes making a dihedral angle of 15.3 (5) degrees . In the crystal, the ions are linked by weak C-H?F inter-actions. PMID- 22058840 TI - Diaqua-tris-[4,4,4-trifluoro-3-oxo-1-(thio-phen-2-yl)but-1-en-1 olato]neodymium(III) acetonitrile monosolvate. AB - The title complex, [Nd(C(8)H(4)F(3)O(2)S)(3)(H(2)O)(2)].CH(3)CN, consists of an Nd(III) ion surrounded by three 4,4,4-trifluoro-3-oxo-1-(thio-phen-2-yl)but-1-en 1-olate ligands, coordinated through the O atoms, and two water mol-ecules. The Nd-O bond lengths range from 2.372 (2) to 2.513 (2) A. The metal ion displays a coordination number of eight and a square-anti-prismatic coordination geometry. A single uncoordinated acetonitrile mol-ecule is present in the asymmetric unit. Two of the three thio-phene rings are disordered, resulting from a 180 degrees rotation with respect to the beta-diketonate moiety. The coordinated water mol ecules act as hydrogen-bond donors towards the acetonitrile N atom and the beta diketonate O atoms. PMID- 22058841 TI - Bis-(chloro-acetato-kappaO)bis(trimethyl-silylmethyl)tin(IV). AB - In the title complex, [Sn(C(2)H(2)ClO(2))(2)(C(4)H(11)Si)(2)], the Sn(IV) ion is coordinated in a distorted tetra-hedral environment formed by two O atoms from two monodenate chloro-acetato ligands and two C atoms from two trimethyl silyl ligands. Two further weak intra-molecular Sn?O contacts [2.744 (2) and 2.655 (2) A] are formed by the chloro-acetato ligands. PMID- 22058842 TI - Di-MU-but-2-enoato-bis-[diaqua-bis(but-2-enoato)neodymium(III)] 2,6-diamino purine disolvate. AB - The title Nd complex [Nd(2)(C(4)H(5)O(2))(6)(H(2)O)(4)].2C(5)H(6)N(6) is isotypic with two previously reported Dy and Ho isologues. It is composed of [Nd(crot)(3)(H(2)O)(2)](2) dimers [crot(onate) = but-2-enoate = C(4)H(5)O(2)], built up around symmetry centres and completed by 2,6-diamine-purine mol-ecules acting as solvates. The neodymium cations are coordinated by three chelating crotonato units and two water mol-ecules. One of the chelating carboxyl-ates acts also in a bridging mode, sharing one oxygen with both cations, and the final result is a pair of NdO(9) tricapped prismatic polyhedra linked to each other through a central (Nd-O)(2) loop. A most attractive aspect of the structures resides in the existence of a complex inter-molecular hydrogen-bonding interaction scheme involving two sets of tightly inter-linked, non-inter-secting one-dimensional structures, one of them formed by the [Nd(crot)(3)(H(2)O)(2)](2) dimers running along [100] and the second by the solvate mol-ecules evolving along [010]. PMID- 22058843 TI - Dichloridobis[2-methyl-sulfanyl-4-(pyridin-2-yl)pyrimidine-kappaN,N]cobalt(II). AB - The asymmetric unit of the title compound, [CoCl(2)(C(10)H(9)N(3)S)(2)], contains one half-mol-ecule with the Co(II) atom situtated on a twofold rotational axis. The Co(II) atom, in an octa-hedral enviroment, is coordinated by four N atoms from two 2-methyl-sulfanyl-4-(pyridin-2-yl)pyrimidine ligands and two Cl atoms. PMID- 22058844 TI - MU-Bromido-bis{MU-2,2'-[4,7-diaza-decane-1,10-diylbis(nitrilo-methanylyl idene)]diphenolato}tricopper(II) bromide dimethyl-formamide disolvate. AB - The complex mol-ecule of the title compound, [Cu(3)Br(C(22)H(28)N(4)O(2))(2)]Br.2C(3)H(7)NO, contains three copper atoms, two of which are five-coordinate within a square-pyramidal environment and linked by a bridging Br atom occupying the apical position in each square pyramid. The remaining Cu atom is four-coordinate but with considerable tetra-hedral disortion [the dihedral angle between the two chelate planes is 69.21 (7) degrees ]. There are two mol-ecules of dimethyl-formamide (DMF) present as solvent mol-ecules, one of which is disordered over two equivalent conformations with occupancies of 0.603 (5) and 0.397 (5). The amine H atoms are involved in both inter- and intra molecular hydrogen-bonding inter-actions with the Br and O atoms of the cation, as well as with the O atom of the ordered DMF mol-ecule. PMID- 22058845 TI - catena-Poly[[bis-[[bis-(3-amino-prop-yl)amine-kappaN,N',N''](thio-cyanato kappaN)cadmium]-MU(4)-sulfato-kappaO,O:O',O'] methanol hemisolvate]. AB - The asymmetric unit of the title compound, {[Cd(2)(NCS)(2)(SO(4))(C(6)H(17)N(3))(2)].0.5CH(3)OH}(n), consists of two Cd(2+) cations, two thio-cyanate and one sulfate anion, two bis-(3-amino-prop-yl)amine co-ligands and one methanol molecule with half-occupancy. Each Cd(2+) cation is coordinated by four N atoms of one terminal N-bonded thio-cyanate anion and one bis-(3-amino-prop-yl)amine co-ligand, and by two O atoms of two symmetry-related sulfate anions, defining a slightly distorted octa-hedral coordination polyhedron. Each two Cd(2+) cations are connected into dimers, which are located on centres of inversion and which are further MU-1,1:3,3-bridged via the sulfate anions into polymeric zigzag chains along the a axis. PMID- 22058846 TI - Bis[2-(2-amino-ethyl-amino)-ethanol]copper(II) dinitrate. AB - In the title compound, [Cu(C(4)H(12)N(2)O)(2)](NO(3))(2), the central Cu(II) atom has a distorted octa-hedral coordination geometry and is surrounded by four N atoms and two O atoms from the two inversion-related 2-(2-amino-ethyl-amino) ethanol ligands. In the crystal, mol-ecules are held together by inter-molecular O-H?O and N-H?O hydrogen bonds, leading to the formation of a three-dimensional network. PMID- 22058847 TI - trans-Dibromidobis(1-ethyl-3-methyl-imidazol-2-yl-idene)palladium(II). AB - The title compound, trans-[PdBr(2)(C(6)H(10)N(2))(2)], was synthesized ionothermally in the ionic liquid solvent 1-ethyl-3-methyl-imidazolium bromide. In the crystal, the Pd(II) atoms are square-planarly coordinated to two Br atoms and two neutral (C(6)H(10)N(2)) ligands. The Pd(II) atom is located on an inversion centre. PMID- 22058848 TI - Bis[4-(1-imino-eth-yl)-3-methyl-1-phenyl-1H-pyrazol-5-olato-kappaO,N]copper(II). AB - In the title complex, [Cu(C(12)H(12)N(3)O)(2)], the Cu(II) ion is tetra coordinated by two N atoms and two O atoms from two bis-chelating 4-(1-imino-eth yl)-3-methyl-1-phenyl-1H-pyrazol-5-olate ligands in a square-planar geometry. The two N atoms and two O atoms around the Cu(II) atom are trans to each other, as the Cu(II) atom lies on an inversion centre. The six-membered ring composed of the Cu, an O, an N and three C atoms of the ligand and the pyrazole ring is nearly planar, the largest deviation being 0.037 (4) A for an N atom. In the crystal, weak inter-molecular C-H?N hydrogen-bonding inter-actions link the mol ecules into chains along the c axis. PMID- 22058849 TI - Bis{2-[(2-hy-droxy-2-methyl-prop-yl)imino-meth-yl]-4-nitro-phenolato}nickel(II) dimethyl-formamide monosolvate. AB - In the title compound, [Ni(C(11)H(13)N(2)O(4))(2)].C(3)H(7)NO, the Ni(II) ion is octa-hedrally coordinated in an N(2)O(4) environment by two identical Schiff base ligands. The Ni-O bond lengths range from 2.004 (2) to 2.106 (2) A, while the Ni N bond lengths are 2.038 (2) and 2.0465 (19) A. The cis bond angles range from 78.64 (8) to 97.30 (8) degrees , with the former being due to the small bite of the amino-alcohol ligand, while the trans bond angles range from 167.86 (8) to 171.23 (8) degrees . One of the alcohol H atoms forms a hydrogen bond with the dimethyl-formamide (DMF) solvent mol-ecule, while the other links mol-ecules into chains along the b axis through inter-molecular O-H?O hydrogen bonds. There are bifurcated C-H?O inter-actions involving one of the nitro groups between parallel stacks of mol-ecules in the b-axis direction. PMID- 22058850 TI - {MU-6,6'-Dimeth-oxy-2,2'-[butane-1,4-diylbis(nitrilo-methanylyl idene)]diphenolato}trinitratocopper(II)samarium(III). AB - In the monomeric dinuclear title complex, [CuSm(C(20)H(22)N(2)O(4))(NO(3))(3)], the four-coordinate Cu(II) ion has a square-planar geometry involving two O atoms and two N atoms of the deprotonated Schiff base ligand. The Sm(III) ion is ten coordinate, chelated by four O donor atoms of the Schiff base and two O atoms each from three bidentate nitrate groups, one of which is disordered over two sites in a 0.55 (7):0.45 (7) ratio. PMID- 22058851 TI - Bis[bis-(diphenyl-phosphino-yl)acetonitrile-kappaO,O']copper(II). AB - The title complex, [Cu(C(26)H(20)NO(2)P(2))(2)], contains a central Cu(II) atom surrounded by two homoleptic bidentate ligands, which form two five-membered chelate rings. The Cu atom binds to four O atoms, resulting in a four-coordinate square-planar complex. The asymmetric unit contains half of the complex, the other half being completed by inversion symmetry. The Cu-O bond lengths have similar distances, viz. 1.9153 (10) A for the pair opposite (trans) each other and 1.9373 (10) A for the other (trans) pair. The P-O bond lengths are 1.5250 (11) A, indicating significant electron delocalization across the O-P-C-P-O atoms in the chelate ring, resulting in a longer P-O bond length when compared to a formal double-bond P=O character (much shorter at approximately 1.47 A). The two inter-secting O-Cu-O angles are both linear at 180 degrees , whilst the remaining L-shaped O-Cu-O bond angles are 88.26 (5) and 91.74 (5) degrees . The C-C N fragment is slightly distorted from linearity at 177.44 (19) degrees and the C N bond length of 1.151 (2) A indicates predominantly triple-bond character. PMID- 22058852 TI - Poly[di-MU-glycinato-copper(II)]: a two-dimensional coordination polymer. AB - The title coordination polymer, [Cu(C(2)H(4)NO(2))(2)](n), is two-dimensional and consists of a distorted octa-hedral copper coordination polyhedron with two bidentate glycine ligands chelating the metal through the O and N atoms in a trans-square-planar configuration. The two axial coordination sites are occupied by carbonyl O atoms of neighbouring glycine mol-ecules. The Cu-O distances for the axial O atoms [2.648 (2) and 2.837 (2) A] are considerably longer than both the Cu-O [1.9475 (17) and 1.9483 (18) A] and Cu-N [1.988 (2) and 1.948 (2) A] distances in the equatorial plane, which indicates a strong Jahn-Teller effect. In the crystal, the two-dimensional networks are arranged parallel to (001) and are linked via N-H?O hydrogen bonds, forming a three-dimensional arrangement. PMID- 22058853 TI - 4-(Dimethyl-amino)-pyridinium tetra-chlorido(quinoline-2-carboxyl-ato kappaN,O)stannate(IV). AB - In the title salt, (C(7)H(11)N(2))[SnCl(4)(C(10)H(6)NO(2))], the Sn(IV) atom is chelated by the N,O-bidentate carboxyl-ate ions and four chloride ions, showing a distorted octa-hedral SnNOCl(4) coordination. In the crystal, the cation and anion are linked by a pyridinium-carboxyl-ate N-H?O hydrogen bond. PMID- 22058854 TI - Bis{4-bromo-2-[(2-hy-droxy-eth-yl)imino-meth-yl]phenolato}nickel(II) monohydrate. AB - The title mononuclear nickel complex, [Ni(C(9)H(9)BrNO(2))(2)].H(2)O, was obtained by the reaction of 5-bromo-salicyl-aldehyde, 2-amino-ethanol and nickel nitrate in methanol. The Ni(II) atom is six-coordinated by two phenolate O, two imine N and two hy-droxy O atoms from two crystallographically different Schiff base ligands, forming an octa-hedral geometry. In the crystal, mol-ecules are linked by inter-molecular O-H?O and O-H?Br hydrogen bonds, forming a three dimensional network. PMID- 22058855 TI - Bis{4-chloro-2-[(2-hy-droxy-eth-yl)imino-meth-yl]phenolato}nickel(II) monohydrate. AB - The title mononuclear nickel(II) complex, [Ni(C(9)H(9)ClNO(2))(2)].H(2)O, was obtained by the reaction of 5-chloro-salicyl-aldehyde, 2-amino-ethanol and nickel nitrate in methanol. The Ni atom is six-coordinated by two phenolate O, two imine N and two hy-droxy O atoms from two crystallographically different Schiff base ligands, forming an octa-hedral geometry. In the crystal, mol-ecules are linked through inter-molecular O-H?O and O-H?Cl hydrogen bonds. PMID- 22058856 TI - Dibromido(2,3-di-2-pyridyl-pyrazine-kappaN,N)platinum(II). AB - The Pt(II) ion in the title complex, [PtBr(2)(C(14)H(10)N(4))], is four coordinated in a distorted square-planar environment by two N atoms of a chelating 2,3-di-2-pyridyl-pyrazine ligand and two bromide anions. In the crystal, the pyridyl ring coordinated to the Pt atom is inclined slightly to its carrier pyrazine ring [dihedral angle = 14.7 (2) degrees ], whereas the uncoordinated pyridyl ring is inclined considerably to the pyrazine ring [dihedral angle = 51.9 (3) degrees ]. The dihedral angle between the two pyridyl rings is 57.7 (3) degrees . Two complex mol-ecules are assembled through inter molecular C-H?N hydrogen bonds, forming a dimer-type species. Intra-molecular C H?Br and C-H?N hydrogen bonds are also present. PMID- 22058857 TI - (eta-Isopropyl N-phenyl-carbamate)(eta-penta-methyl-cyclo-penta-dien yl)ruthenium(II) tetra-phenyl-borate acetone monosolvate. AB - The title complex, [Ru(C(10)H(15))(C(10)H(13)NO(2))](C(24)H(20)B).C(3)H(6)O, is related to the analogous O-methyl complex. The average Ru-C distance to the penta methyl-cyclo-penta-dienyl (Cp*) group is 2.19 (3) A, and 2.21 (1) A to the ortho, meta and para C atoms of the arene ring. The Ru-C(ipso) bond length of 2.272 (3) A is significantly longer, reflecting movement of the Ru atom away from the C atoms with electronegative substituents attached. The amide H atom in the cation forms an inter-molecular N-H?O hydrogen bond with the carbonyl O atom of the acetone solvent mol-ecule. A C-H?O inter-action also occurs. PMID- 22058858 TI - Tetra-kis(MU-2-phen-oxy-propionato)-kappaO,O':O';kappaO:O,O';kappaO:O'-bis-[(1,10 phenanthroline-kappaN,N')(2-phen-oxy-propionato-kappaO,O')terbium(III)]. AB - In the centrosymmetric binuclear title complex, [Tb(2)(C(9)H(9)O(3))(6)(C(12)H(8)N(2))(2)], the two Tb(III) ions are linked by four 2-phen-oxy-propionate (L) groups through their bi- and tridentate bridging modes. Each Tb(III) ion is nine-coordinated by one 1,10-phenanthroline mol-ecule, one bidentate carboxyl-ate group and four bridging carboxyl-ate groups in a distorted TbN(2)O(7) monocapped square-anti-prismatic geometry. PMID- 22058859 TI - catena-Poly[[tetra-kis-(MU-penta-fluoro-benzoato-kappaO:O')dimolybdenum(II)]-MU 4,4'-bipyridine-kappaN:N']. AB - In the title compound, [Mo(2)(C(7)F(5)O(2))(4)(C(10)H(8)N(2))](n), the mol-ecule forms a paddle-wheel-type structure. Each Mo(2) (4+) unit is equatorially coordinated by four pentafluoro-benzoate groups, while the axial positions are occupied by two 4,4'-bipyridine mol-ecules. The Mo-Mo bond length of 2.1227 (4) A is representative of a dimolybdenum quadruple bond. An infinite linear chain parallel to [110] is formed by the Mo(2) (4+) unit coordinating axially to the two N atoms of the 4,4'-bipyridine ligand [Mo-N = 2.594 (2) A]. The crystal packing shows mol-ecules linked together into a three-dimensional network via Mo N coordination inter-actions and weak pi-pi stacking inter-actions between perfluoro-phenyl rings [centroid-centroid distance = 3.7280 (3) A and centroid-to plane distance = 3.6103 (12) A between two penta-fluoro-phenyl rings]. PMID- 22058860 TI - Diacetato-kappaO;kappaO,O'-aqua-(2,4,6-tri-2-pyridyl-1,3,5-triazine kappaN,N,N)manganese(II) monohydrate. AB - The Mn(II) ion in the title compound, [Mn(CH(3)CO(2))(2)(C(18)H(12)N(6))(H(2)O)].H(2)O, is seven-coordinated in an approximately penta-gonal-bipyramidal geometry by three N atoms of the tridentate 2,4,6-tri-2-pyridyl-1,3,5-triazine ligand and four O atoms from two distinct anionic acetato ligands and a water mol-ecule. One acetate anion chelates the Mn atom via two O atoms occupying equatorial positions, and the other anion coordinates the Mn atom as a monodentate ligand via one O atom. The complex and solvent water mol-ecules are linked by inter- and intra-molecular O-H?O, O-H?N and C-H?O hydrogen bonds into a three-dimensional network. PMID- 22058861 TI - Di-MU-acetato-kappaO,O':O';kappaO:O,O'-bis-[(acetato-kappaO,O')bis-(5-nitro-1,10 phenanthroline-kappaN,N')cadmium]. AB - In the binuclear title compound, [Cd(2)(C(2)H(3)O(2))(4)(C(12)H(7)N(3)O(2))(2)], the Cd(II) cations are linked by carboxyl-ate O atoms into a four-membered Cd(2)O(2) rhombic ring with a Cd? Cd separation of 3.7515 (5) A. Each Cd(II) atom is seven-coordinated by a bidentate 5-nitro-1,10-phenanthroline (5-NO(2)-phen) ligand and two bidentate acetate anions, one of which also acts as a bridge linking the two Cd atoms. The crystal packing is stabilized by pi-pi inter actions between the phen rings of neighboring mol-ecules, with centroid-centroid distances of 3.491 (2) (intra-molecular) and 3.598 (2) A (inter-molecular). PMID- 22058862 TI - Poly[diaqua-(MU-4,4'-bipyridine-kappaN:N')[MU-2,2'-(p-phenyl-enedi-oxy)diacetato kappaO:O']cadmium]. AB - In the title compound, [Cd(C(10)H(8)O(6))(C(10)H(8)N(2))(H(2)O)(2)](n), the Cd(II) ion has inversion symmetry and is coordinated by O atoms from two water mol-ecules and two bridging 2,2'-(MU-p-phenyl-enedi-oxy)diacetate ligands and two N atoms from two 4,4'-bipyridine ligands, giving a slightly distorted octa-hedral geometry. The diacetate and 4,4'-bipyridine ligands also lie across inversion centers. The bridging ligands form layers parallel to (11[Formula: see text]), with adjacent layers inter-connected via O-H?O hydrogen bonds between the coordinated water mol-ecules and the carboxyl-ate O atoms, giving a three dimensional supra-molecular architecture. PMID- 22058863 TI - catena-Poly[[aqua-bis-(N-benzyl-adenine-kappaN)copper(II)]-MU-benzene-1,4 dicarboxyl-ato-kappaO:O]. AB - In the title compound, [Cu(C(8)H(4)O(4))(C(12)H(11)N(5))(2)(H(2)O)](n), the Cu(II) ion is five-coordinated by two carboxyl-ate O atoms from two symmetry related benzene-1,4-dicarboxyl-ate ligands, two N atoms from two symmetry-related N(6)-benzyl-adenine ligands and one water O atom in a square-pyramidal environment. The Cu(II) and water O atoms lie on a twofold rotation axis, and the benzene-1,4-dicarboxyl-ate ligand lies on an inversion center. The water O atom occupies the apical position and the basal plane is occupied by two O atoms and two N atoms. Each benzene-1,4-dicarboxyl-ate anion acts as a bis-monodentate ligand that binds two Cu(II) cations, forming an infinite chain extending parallel to [001]. The N(6)-benzyl-adenine ligands are attached on both sides of the chain. Neighboring chains are further inter-connected into the resulting three-dimensional supra-molecular architecture via O-H?O, N-H?O and N-H?N hydrogen bonds. PMID- 22058864 TI - Tetra-aqua-{1-[(1H-1,2,3-benzotriazol-1-yl)meth-yl]-1H-1,2,4-triazole}sulfato cadmium dihydrate. AB - In the title complex, [Cd(SO(4))(C(9)H(8)N(6))(H(2)O)(4)].2H(2)O, the Cd(II) ion is six-coordinated by one N atom from a 1-[(1H-1,2,3-benzotriazol-1-yl)meth-yl] 1H-1,2,4-triazole ligand and by five O atoms from four water mol-ecules and one monodentate sulfate anion in a distorted octa-hedral geometry. The sulfate tetra hedron is rotationally disordered over two positions in a 0.651 (12):0.349 (12) ratio. In the crystal, adjacent mol-ecules are linked through O-H?O and O-H?N hydrogen bonds into a three-dimensional network. PMID- 22058865 TI - (MU-Formato-kappaO:O')bis-[dicarbon-yl(eta-cyclo-penta-dien-yl)iron(II)] tetra fluoridoborate. AB - In the structure of the title compound [Fe(2)(C(5)H(5))(2)(CHO(2))(CO)(4)]BF(4), each Fe(II) atom is coordinated in a pseudo-octa-hedral three-legged piano-stool fashion. The cyclo-penta-dienyl ligand occupies three fac coordination sites while the two carbonyl ligands and formate O atom occupy the remaining three sites. PMID- 22058866 TI - catena-Poly[[diaqua-copper(II)]-MU-hy-drox-ido-kappaO:O-MU-[4-(4H-1,2,4-triazol-4 yl)benzoato]-kappaN:N]. AB - The title compound, [Cu(C(9)H(6)N(3)O(2))(OH)(H(2)O)(2)](n), adopts a chain motif along [010] in which the Cu(II) atoms are bridged by hy-droxy groups and 4-(1,2,4 triazol-4-yl)benzoate (tab) ligands. The Cu(II) atom lies on an inversion center and is six-coordinated by two N atoms from two tab ligands, two hy-droxy groups and two water mol-ecules, giving a distorted octa-hedral geometry. The hy-droxy group and the tab ligand are located on a mirror plane. One of the water H atoms is disordered over two positions with equal occupancy factors. Inter-molecular O H?O hydrogen bonds extend the chains into a layer parallel to (100) and C-H?O hydrogen bonds connect the layers into a three-dimensional network. PMID- 22058867 TI - trans-Diaqua-bis-[4-carboxy-5-carboxyl-ato-2-(pyridin-1-ium-4-yl)-1H-imidazol-1 ido-kappaN,O]cobalt(II). AB - In the title compound, [Co(C(10)H(6)N(3)O(4))(2)(H(2)O)(2)], the Co(II) ion is coordinated by two O atoms of two water mol-ecules, two imidazole nitro-gen atoms and two carboxyl-ate O atoms of the two trans-standing chelate ligands, displaying a distorted octa-hedral coordination geometry. A three-dimensional supra-molecular framework is generated through N-H?O, O-H?N and O-H?O hydrogen bonding inter-actions. PMID- 22058868 TI - [2-((R)-{2-[(S)-1-Benzylpyrrolidin-2-ylcarbonylazanidyl]-phen-yl}(phen-yl)methyl idene-amino)-4-hy-droxy-butano-ato-kappaN,N',N'',O]nickel(II) toluene disolvate. AB - The central Ni atom in the title compound, [Ni(C(29)H(29)N(3)O(4))].2C(7)H(8), is coordinated in a distorted square-planar environment by three N atoms [Ni-N = 1.942 (3), 1.843 (3) and 1.853 (3) A] and one O atom [1.868 (3) A] of the tetradentate ligand. The conformation of the hy-droxy-butano-ate side chain is controlled by an inter-molecular hydrogen bond. PMID- 22058869 TI - cyclo-Tetra-kis(MU-3-acetyl-4-methyl-1H-pyrazole-5-carboxyl-ato kappaN,O:N,O)tetra-kis[aqua-copper(II)] tetra-deca-hydrate. AB - The title compound, [Cu(4)(C(7)H(6)N(2)O(3))(4)(H(2)O)(4)].14H(2)O, a tetra nuclear [2 * 2] grid-type complex with S4 symmetry, contains four Cu(II) atoms which are bridged by four pyrazole-carboxyl-ate ligand anions and are additionally bonded to a water molecule. Each Cu(II) atom is coordinated by two O atoms of the carboxyl-ate and acetyl groups, two pyrazole N atoms of doubly deprotonated 3-acetyl-4-methyl-1H-pyrazole-5-carb-oxy-lic acid and one O atom of a water mol-ecule. The geometry at each Cu(II) atom is distorted square pyramidal, with the two N and two O atoms in the equatorial plane and O atoms in the axial positions. O-H?O hydrogen-bonding interactions additionally stabilize the structure. One of the uncoordinated water molecules shows half-occupancy. PMID- 22058870 TI - Diaqua-bis-(2-hy-droxy-5-meth-oxy-benzoato-kappaO)zinc. AB - The title compound, [Zn(C(8)H(7)O(4))(2)(H(2)O)(2)], has been synthesized by hydro-thermal methods. The Zn(II) atom, whose symmetry element is a twofold axis, is four coordinated by two O atoms from 5-meth-oxy-salicylate anions and two aqua O atoms in a distorted tetra-hedral geometry. In the crystal, mol-ecules are linked into a layer by O-H?O hydrogen bonds, which stabilize the packing. PMID- 22058871 TI - Bis(N,N'-dimethyl-ethylenediammonium) tris-(oxalato-kappaO,O)cobaltate(II) dihydrate: an ion-pair complex. AB - The Co(II) ion in the title complex, (C(4)H(14)N(2))(2)[Co(C(2)O(4))(3)].2H(2)O, is coordinated by three oxalate ions, resulting in a distorted octa-hedral geometry. Two uncoordinated water mol-ecules are present in asymmetric unit. Inter-molecular N-H?O and O-H?O hydrogen bonds between the different entities stabilize the crystal structure. PMID- 22058872 TI - trans-Chlorido(phenanthren-9-yl)bis-(triphenyl-phosphane)nickel(II). AB - The title compound, [Ni(C(14)H(9))Cl(C(18)H(15)P)(2)], was synthesized from the reaction between 9-chloro-phenanthrene, NiCl(2).6H(2)O and triphenyl-phosphane in ethanol. The bond angles around the Ni(II) atom indicate that it exists in a slightly distorted square-planar geometry. PMID- 22058873 TI - Dichlorido[3-meth-oxy-methyl-4-phenyl-5-(2-pyrid-yl)-4H-1,2,4-triazole kappaN,N]copper(II). AB - In the title complex, [CuCl(2)(C(15)H(14)N(4)O)], the Cu(II) atom possesses a highly distorted square-planar geometry with N-Cu-N and Cl-Cu-Cl angles of 79.86 (8) and 98.65 (3) degrees , respectively, while the Cl-Cu-N angles fall into two distinct groups with values of 95.26 (6), 98.75 (6), 150.56 (6) and 152.04 (6) degrees . The pyridyl ring is twisted by 9.4 (2) degrees with respect to the triazole ring, which is oriented at approximately right angles [84.66 (8) degrees ] with respect to the phenyl ring. PMID- 22058874 TI - A cationic rhodium(I) N-heterocyclic carbene complex isolated as an aqua adduct. AB - The title complex, aqua-[1,3-bis-(2,6-diiso-propyl-phen-yl)imid-az-ol-2-yl idene](eta(4)-cyclo-octa-1,5-diene)rhodium(I) tetra-fluor-ido-borate, [Rh(C(8)H(12))(C(27)H(36)N(2))(H(2)O)]BF(4), exihibits a square-planar geometry around the Rh(I) atom, formed by a bidentate cyclo-octa-1,5-diene (cod) ligand, an N-heterocylcic carbene and an aqua ligand. The complex is cationic and a BF(4) (-) anion balances the charge. The structure exists as a hydrogen-bonded dimer in the solid state, formed via inter-actions between the aqua ligand H atoms and the BF(4) (-) F atoms. PMID- 22058875 TI - catena-Poly[[cadmium-bis-(MU-triethyl-ene-tetra-mine-kappaN,N':N'',N''')-cadmium (MU-triethyl-ene-tetra-mine-kappaN,N':N'',N''')] hexa-fluoridogermanate]. AB - The title fluoridogermanate, {[Cd(2)(C(6)H(18)N(4))(3)][GeF(6)]}(n), was synthesized hydro-thermally. The crystal structure comprises undulated cationic [Cd(2)(TETA)(3)](4+) chains (TETA is triethyl-ene-tetra-mine) propagating parallel to [101]. The central Cd(II) atom is six-coordinated in a CdN(6) set by three TETA ligands. The isolated [GeF(6)](2-) units, serving as counter-anions, occupy the inter-chain spaces and simultaneously link adjacent chains into a three-dimensional network through extensive N-H?F hydrogen-bonding inter-actions. One of the ethyl-ene bridges of one TETA ligand is disordered around a twofold rotation axis. PMID- 22058876 TI - 8-Hy-droxy-2-methyl-quinolinium dichlorido(2-methyl-quinolin-8-olato kappaN,O)zincate acetonitrile disolvate. AB - The reaction of 2-methyl-8-hy-droxy-quinoline and zinc chloride in acetonitrile affords the title solvated salt, (C(10)H(10)NO)[Zn(C(10)H(8)NO)Cl(2)].2CH(3)CN, in which the Zn(II) atom is coordinated by an- N,O-chelating 2-methyl-quinolin-8 olate ligand and two chloride ligands in a distorted tetra-hedral geometry. The cation is linked to the heterocyclic anion by an O-H?O hydrogen bond and the quinolinium H atom forms a inter-molecular N-H?N hydrogen bond with one of the acetonitrile solvent mol-ecules. PMID- 22058877 TI - 8-Hy-droxy-2-methyl-quinolinium dibromido(2-methyl-quinolin-8-olato kappaN,O)zincate acetonitrile mono-solvate. AB - The reaction of 2-methyl-8-hy-droxy-quinoline and zinc bromide in acetonitrile affords the title solvated salt, (C(10)H(10)NO)[ZnBr(2)(C(10)H(8)NO)].CH(3)CN, in which the Zn(II) ion is coordinated by a N,O-chelating 2-methyl-quinolin-8-olate ligand and two bromide ligands in a distorted tetra-hedral geometry. The cation is linked to the anion by an O-H?O hydrogen bond and the quinolinium H atom forms an inter-molecular N-H?N hydrogen bond with the acetonitrile solvent mol-ecule. PMID- 22058878 TI - Chlorido(8-hy-droxy-quinoline-kappaN,O)(quinolin-8-olato-kappaN,O)zinc methanol monosolvate. AB - In the title compound, [Zn(C(9)H(6)NO)Cl(C(9)H(7)NO)].CH(3)OH, the Zn(II) ion is N,O-chelated by both a neutral and a deprotonated quinolin-8-ol ligand, with a chloride ligand in the apical site completing the square-pyramidal coordination geometry. The Zn(II) ion is displaced by 0.586 A in the direction of the chloride ligand from the atoms forming the square plane. In the crystal, the components are linked by inter-molecular O-H?O hydrogen bonds, generating chains along the b axis. PMID- 22058879 TI - A double salt of iodo-bis-muthate: cis-aqua-iodidobis(1,10 phenanthroline)cobalt(II) tris-(1,10-phenanthroline)cobalt(II) trans-hexa-MU(2) iodido-hexa-iodidotribismuthate(III). AB - In the title complex, [Co(C(12)H(8)N(2))(3)][CoI(C(12)H(8)N(2))(2)(H(2)O)][Bi(3)I(12)], conventionally abbreviated [Co(phen)(3)][CoI(phen)(2)(H(2)O)][Bi(3)I(12)], where phen is 1,10 phenanthroline, the Co(II) atom in one cation is coordinated by six N atoms from three phen ligands in an octa-hedral coordination while the Co(II) atom in the other cation is coordinated octa-hedrally by four N atoms from two phen ligands, one water O atom and one I atom. In the anion, three Bi(III) ions adopt an octa hedral coordination constructed by six I(-) ligands. The three BiI(6) octa-hedra are fused together through trans face-sharing. PMID- 22058880 TI - trans-Carbonyl-chloridobis[dicyclo-hex-yl(4-isopropyl-phen yl)phosphane]rhodium(I) acetone monosolvate. AB - The title rhodium Vaska-type complex, trans-[RhCl{P(C(6)H(11))(2)(C(6)H(4)-4 C(3)H(7))(2)}(2)(CO)], crystallizes with an accompanying acetone solvent mol ecule. The metal atom shows a distorted square-planar coordination environment with selected important geometrical parameters of Rh-P = 2.3237 (6) and 2.3253 (6) A, Rh-Cl = 2.3724 (6) A, Rh-C = 1.802 (2) A, P-Rh-P = 173.42 (2) degrees and Cl-Rh-C = 179.13 (7) degrees . Effective cone angles for the two P atoms are 165 and 161 degrees , respectively. Both isopropyl groups and the acetone mol-ecule are disordered with occupancy values of 0.523 (5):0.477 (5), 0.554 (8):0.446 (8) and 0.735 (4):0.265 (4), respectively. The crystal packing is stabilized by weak C-H?O and C-H?Cl contacts. PMID- 22058881 TI - catena-Poly[copper(I)-bis-[MU-3-(1H-imidazol-2-yl)pyridine]-copper(I)-di-MU iodido]. AB - The title polymeric compound, [Cu(2)I(2)(C(8)H(7)N(3))(2)](n) [C(8)H(7)N(3) = 3 (1H-imidazol-2-yl)pyridine (HIPy), where HIPy comes from the in situ deca rboxylation of 2-(pyridin-3-yl)-1H-imidazole-4,5-dicarb-oxy-lic acid (H(3)PyIDC)], was obtained under solvo-thermal conditions. Each Cu(I) cation is in a distorted tetra-hedral coordination environment defined by two iodide anions and two nitro-gen atoms from two individual HIPy ligands. Two Cu(I) atoms are connected by two HIPy ligands to form a dimer and these dimers are further bridged through the iodide atoms, leading to a chain structure extending parallel to [100]. Moreover, inter-molecular N-H?I hydrogen bonds and weak pi-pi stacking inter-actions [centroid?centroid distances of 3.809 (4) A, an inter-planar separation of 3.345 (3) A and a ring slippage of 1.822 A] between pyridyl rings link the chains into a two-dimensional supra-molecular network in the ac plane. PMID- 22058882 TI - Tetra-kis(MU-penta-fluoro-benzoato-kappaO:O')bis-[(tetra-hydro-furan kappaO)molybdenum(II)]. AB - In the asymmetric unit of the title compound, [Mo(2)(C(7)F(5)O(2))(4)(C(4)H(8)O)(2)], two independent half-mol-ecules are present, which are completed by a crystallographically imposed center of inversion between the individual Mo atoms. In each mol-ecule, four penta-fluoro benzoate anions bridge the quadruply bonded Mo(2) (4+) unit that is, in addition, axially coordinated by two O atoms of tetra-hydro-furan (THF) mol-ecules. In the two independent mol-ecules, the mean Mo-Mo bond length is 2.110 A. Since the THF mol-ecules are equally disordered over two sets of sites, there are four different Mo-O distances in both half-mol-ecules with an overall mean of 2.542 A. A zigzag chain is formed by pi-pi stacking inter-actions between penta-fluoro phenyl rings, indicated by a centroid-centroid distance of 3.7054 (11) A and a centroid-to-plane distance of 3.4169 (3) A. The extension of the unit gives a three-dimensional network structure with the THF mol-ecules located in the voids. PMID- 22058883 TI - catena-Poly[[[triaqua-europium(III)]-MU-(1H-benzimidazole-5,6-dicarboxyl-ato kappaO:O)-MU-(1H,3H-benzimidazol-3-ium-5,6-dicarboxyl-ato-kappaO:O,O)] dihydrate]. AB - In the title one-dimensional coordination polymer, {[Eu(C(9)H(4)N(2)O(4))(C(9)H(5)N(2)O(4))(H(2)O)(3)].2H(2)O}(n), one of the 1H benzimidazole-5,6-dicarboxyl-ate (Hbdc) ligands is protonated at the imidazole group (H(2)bdc). The Eu(III) ion is eight-coordinated by two O atoms from two Hbdc ligands, three O atoms from two H(2)bdc ligands and three water mol-ecules, showing a distorted square-anti-prismatic geometry. The Eu(III) ions are bridged by the carboxyl-ate groups of the Hbdc and H(2)bdc ligands, forming a chain along [110], with an Eu?Eu separation of 5.4594 (3) A. These chains are further connected by inter-molecular O-H?O, N-H?O and N-H?N hydrogen bonds, as well as pi pi inter-actions between the imidazole and benzene rings [centroid-centroid distances = 3.558 (3), 3.906 (2), 3.397 (3), 3.796 (2) and 3.898 (2) A], into a three-dimensional supra-molecular network. PMID- 22058884 TI - Di-MU-chlorido-bis-(chlorido{2-[(4-ethyl-phen-yl)imino-meth-yl]pyridine kappaN,N'}copper(II)). AB - The binuclear title complex, [Cu(2)Cl(4)(C(14)H(14)N(2))(2)], is located on a crystallographic inversion centre. The Cu(II) ion is in a distorted square pyramid coordination environment formed by the bichelating N-heterocyclic ligand, two bridging Cl atoms and one terminal Cl atom. One of the bridging Cu-Cl bonds is significantly longer than the other. PMID- 22058885 TI - 1-Bromo-methyl-1,4-diazo-niabicyclo-[2.2.2]octane tetra-chloridozincate. AB - The reaction of 1-bromo-methyl-1,4-diazo-niabicyclo-[2.2.2]octane bromide, zinc chloride and hydro-chloric acid in water yields the title compound, (C(7)H(15)BrN(2))[ZnCl(4)]. In the crystal, the components are linked by N-H?Cl hydrogen bonds. The Zn(II) atom has an approximately tetra-hedral coordination geometry. PMID- 22058886 TI - Poly[[[MU(3)-5-(pyridine-4-carboxamido)-isophthalato]{MU(3)-5-[(pyridin-1-ium-4 yl)carbonyl-amino]-isophthalato}-neodymium(III)] dihydrate]. AB - In the title compound, {[Nd(C(14)H(9)N(2)O(5))(C(14)H(8)N(2)O(5))].2H(2)O}(n), the Nd(III) atom is eight-coordinated as it is surrounded by eight carboxyl-ate O atoms from six ligands in a distorted square-anti-prismatic arrangement. The Nd(III) atoms are linked by HL(-) and L(2-) ligands [H(2)L is 5-(pyridine-4 carboxamido)-isophthalic acid], forming a bilayer network. The layers are linked into a three-demensional network through N-H?O and O-H?O hydrogen bonds. PMID- 22058887 TI - Tris(3-amino-pyrazine-2-carboxyl-ato-kappaN,O)diaqua-erbium(III) tetra-hydrate. AB - The water-coordinated Er(III) atom in the title compound, [Er(C(5)H(4)N(3)O(2))(3)(H(2)O)(2)].4H(2)O, is N,O-chelated by three 3-amino pyrazine-2-carboxyl-ate ions and has a square-anti-prismatic geometry. The mononuclear mol-ecule inter-acts with the solvent water mol-ecules to generate a three-dimensional hydrogen-bonded network. PMID- 22058888 TI - Poly[[(MU-3-amino-pyrazine-2-carboxyl-ato-kappaN,O:O')diaqua-(MU-oxalato kappaO,O:O,O)lanthanum(III)] monohydrate]. AB - The water-coordinated La(III) atom in the title compound, {[La(C(5)H(4)N(3)O(2))(C(2)O(4))(H(2)O)(2)].H(2)O}(n), is N,O-chelated by a 3 amino-pyrazine-2-carboxyl-ate ion; this ion links adjacent metal atoms to form a chain parallel to [010]. The oxalate ion serves as a bis-bidentate chelate that links adjacent metal atoms to form a chain parallel to [001]. The two bridging ions give rise to a layer motif parallel to (100) in which the La(III) atom exists in a distorted tricapped trigonal prismatic geometry. Extensive hydrogen bonding between the constituents stabilizes the structure. PMID- 22058889 TI - catena-Poly[copper(II)-bis-(MU-2-ethyl-5-methyl-imidazole-4-sulfonato kappaN,O:O)]. AB - In the title compound, [Cu(C(6)H(9)N(2)O(3)S)(2)](n), the copper(II) ion sits on an inversion center and is chelated by the imidazole N and sulfonate O atoms of two ligands in equatorial positions. O atoms of adjacent mol-ecules coordinate in the axial positions. Jahn-Teller tetra-gonal distortion is evident in the coordination geometry [Cu-N and Cu-O equatorial distances of 1.971 (3) and 2.045 (2) A, respectively, with a Cu-O axial distance of 2.433 (3) A]. The structure is propagated by an infinite chain of eight-membered (Cu-O-S-O)(2) ring systems along the a axis. Only N-H?O hydrogen bonding exists between the chains. PMID- 22058890 TI - (Acetyl-acetonato-kappaO,O')bis-[2-(naphth[1,2-d][1,3]oxazol-2-yl)phenyl kappaC,N]iridium(III). AB - In the crystal structure of the title compound, [Ir(C(17)H(10)NO)(2)(C(5)H(7)O(2))], the Ir(III) atom is O,O'-chelated by the acetyl-acetonate group and C,N-chelated by the 2-aryl-naphth[1,2-d]oxazole groups. The six-coordinate metal atom displays a distorted octa-hedral geometry. PMID- 22058891 TI - Dibromido(2,3-di-2-pyridyl-pyrazine-kappaN,N)platinum(II). AB - The Pt(II) ion in the title complex, [PtBr(2)(C(14)H(10)N(4))], has a slightly distorted square-planar environment defined by the two pyridyl N atoms of the chelating 2,3-di-2-pyridyl-pyrazine ligand and two bromide anions. In the crystal, the pyridyl rings are considerably inclined to the least-squares plane of the PtBr(2)N(2) unit [maximum deviation = 0.064 (2) A] with dihedral angles of 65.2 (2) and 66.0 (2) degrees . The nearly planar pyrazine ring [maximum deviation = 0.020 (5) A] is almost perpendicular to the unit plane with a dihedral angle of 89.2 (2) degrees . Two independent weak inter-molecular C-H?Br hydrogen bonds, both involving the same Br atom as a hydrogen-bond acceptor, give rise to chains running along the a and b axes, forming a layer structure extending parallel to (001). The complexes are stacked in columns along the a axis. When viewed down the b axis, the successive complexes stack in the opposite direction. PMID- 22058892 TI - A one-dimensional triaqua-europium(III)-1H,3H-benzimidazol-3-ium-5,6-dicarboxyl ate-sulfate polymeric structure. AB - In the title coordination polymer, catena-poly[[[triaqua-europium(III)]-bis-(MU 1H,3H-benzimidazol-3-ium-5,6-dicarb-oxyl-ato-kappa(3)O(5),O(5'):O(6))-[triaqua europium(III)]-di-MU-sulfato-kappa(3)O:O,O';kappa(3)O,O':O'] hexahydrate], [Eu(2)(C(9)H(5)N(2)O(4))(2)(SO(4))(2)(H(2)O)(6)].6H(2)O}(n), the 1H,3H benzimidazol-3-ium-5,6-dicarb-oxy-l-ate ligand is protonated at the imidazole group (H(2)bdc). The Eu(III) ion is coordinated by nine O atoms from two H(2)bdc ligands, two sulfate anions and three water mol-ecules, displaying a bicapped trigonal prismatic geometry. The carboxyl-ate groups of the H(2)bdc ligands and the sulfate anions link the Eu(III) ions, forming a chain along [010]. These chains are further connected by N-H?O and O-H?O hydrogen bonds and pi-pi inter actions between the imidazole and benzene rings [centroid-centroid distances = 3.997 (4), 3.829 (4) and 3.573 (4) A] into a three-dimensional supra-molecular network. PMID- 22058893 TI - Poly[MU-aqua-diaqua(MU(3)-1H-benzimid-azole-5-carboxylato-kappaN:O,O')(MU(2)-1H benzimidazole-5-carboxylato-kappaN:O:O')-MU(5)-sulfato-MU(4)-sulfato-tri cadmium]. AB - The asymmetric unit of the title compound, [Cd(3)(C(8)H(5)N(2)O(2))(2)(SO(4))(2)(H(2)O)(3)](n), contains three Cd(II) ions, two sulfate anions, two 1H-benzimidazole-5-carboxyl-ate (H(2)bic) ligands and three coordinated water mol-ecules. One Cd(II) ion is six-coordinated and exhibits a distorted octa-hedral geometry, while the other two Cd(II) ions are seven-coordinated, displaying a distorted penta-gonal-bipyramidal geometry. The Cd(II) ions are bridged by two types of sulfate anions, producing inorganic chains along [100]. These chains are further connected by the H(2)bic ligands, leading to a three-dimensional framework. N-H?O and O-H?O hydrogen bonds and pi pi inter-actions between the imidazole and benzene rings [centroid-centroid distances = 3.953 (2), 3.507 (2), 3.407 (2) and 3.561 (2) A] further stabilize the crystal structure. PMID- 22058894 TI - Diaqua-bis-(4-bromo-benzoato-kappaO)bis-(N,N-diethyl-nicotinamide kappaN)copper(II). AB - The title Cu(II) complex, [Cu(C(7)H(4)BrO(2))(2)(C(10)H(14)N(2)O)(2)(H(2)O)(2)], contains two 4-bromo-benzoate (PBB), two diethyl-nicotinamide (DENA) monodentate ligands and two water mol-ecules. The four O atoms in the equatorial plane around the Cu(II) ion form a slightly distorted square-planar arrangement, while the slightly distorted octa-hedral coordination is completed by two N atoms of the DENA ligands in the axial positions. Intra-molecular O-H?O hydrogen bonds link the water mol-ecules to the carboxyl-ate groups. The dihedral angles between the carboxyl-ate groups and the adjacent benzene rings are 3.1 (3) and 3.74 (17) degrees , while the pyridine rings and the benzene rings are oriented at dihedral angles of 6.81 (10) and 3.38 (12) degrees . In the crystal, inter-molecular O-H?O hydrogen bonds link the mol-ecules into double chains along the b axis. C-H?O inter-actions are also observed. pi-pi contacts between pyridine rings [centroid centroid distance = 3.485 (2) A] may further stabilize the crystal structure. PMID- 22058895 TI - Tetra-kis(MU-2-phen-oxy-propionato)-kappaO,O':O';kappaO:O,O',kappaO:O'-bis-[(1,10 phenanthroline-kappaN,N')(2-phen-oxy-propionato-kappaO,O')dysprosium(III)]. AB - In the centrosymmetric binuclear title complex, [Dy(2)(C(9)H(9)O(3))(6)(C(12)H(8)N(2))(2)], the two Dy(III) ions are linked by four 2-phen-oxy-propionate (L) groups through their bi- and tridentate bridging modes. Each Dy(III) ion is nine-coordinated by one 1,10-phenanthroline mol-ecule, one bidentate carboxyl-ate group and four bridging carboxyl-ate groups in a distorted DyN(2)O(7) monocapped square-anti-prismatic geometry. The title compound is isotypic with its terbium-containing analogue. PMID- 22058896 TI - Tetra-kis(MU-2-phen-oxy-propionato)-kappaO,O':O';kappaO:O,O',kappaO:O'-bis-[(1,10 phenanthroline-kappaN,N')(2-phen-oxy-propionato-kappaO,O')praseodymium(III)]. AB - In the centrosymmetric binuclear title complex, [Pr(2)(C(9)H(9)O(3))(6)(C(12)H(8)N(2))(2)], the two Pr(III) ions are linked by four 2-phen-oxy-propionate (L) groups through their bi- and tridentate bridging modes. Each Pr(III) ion is nine-coordinated by one 1,10-phenanthroline mol-ecule, one bidentate carboxyl-ate group and four bridging carboxyl-ate groups in a distorted PrN(2)O(7) monocapped square-anti-prismatic geometry. The title compound is isotypic with its terbium- and dysprosium-containing analogues. PMID- 22058897 TI - Bis(MU(2)-pyridine-2-carboxamide oximato)bis-[(pyridine-2-carboxamide oxime)zinc] dinitrate. AB - In the title dinuclear compound, [Zn(2)(C(6)H(6)N(3)O)(2)(C(6)H(7)N(3)O)(2)](NO(3))(2), the Zn(II) cation is N,N' chelated by one pyridine-2-carboxamide oximate anion and one pyridine-2 carboxamide oxime mol-ecule, and is further bridged by an oxime O atom from the adjacent pyridine-2-carboxamide oximate anion, forming a distorted trigonal bipyramidal coordination. Two pyridine-2-carboxamide oximate anions bridge two Zn(II) cations to form the centrosymmetric dinuclear mol-ecule. Extensive O-H?O, N-H?O and O-H?N hydrogen bonds are present in the crystal structure. PMID- 22058898 TI - Bis(benzyl-trimethyl-ammonium) tetra-bromidocuprate(II). AB - In the title mol-ecular salt, (C(10)H(16)N)(2)[CuBr(4)], the Cu(II) ion adopts a squashed tetra-hedral geometry with Br-Cu-Br angles varying between 99.29 (3) and 132.53 (3) degrees . In the crystal, the components are linked by C-H?Br inter actions, thereby generating a three-dimensional network. PMID- 22058899 TI - (2E,4E)-1-(2-Hy-droxy-phen-yl)-5-phenyl-penta-2,4-dien-1-one. AB - In the structure of the title chalcone, C(17)H(14)O(2), derived from cinnamaldehyde, the olefine group has a trans configuration. The mol-ecular conformation is stabilized by an intra-molecular O-H?O hydrogen-bond inter-action with graph-set motif S(6). PMID- 22058900 TI - Methyl 2,2'-dimethyl-4'-[2-(methyl-sulfan-yl)eth-yl]-1,3-dioxo-2,3-dihydro-1H,4'H spiro-[isoquinoline-4,5'-oxazole]-4'-carboxyl-ate. AB - In the isoquinoline ring system of the title mol-ecule, C(18)H(20)N(2)O(5)S, the fused N-heterocyclic ring is distorted towards a half-boat conformation. The methyl formate moiety is disordered over two sets of sites with refined occupancies of 0.882 (5) and 0.118 (5). In the crystal, mol-ecules are linked via weak inter-molecular C-H?O hydrogen bonds into one-dimensional chains along [010]. PMID- 22058901 TI - 2-(3,3,4,4-Tetra-fluoro-pyrrolidin-1-yl)aniline. AB - In the title fluorinated pyrrolidine derivative, C(10)H(10)F(4)N(2), the dihedral angle between the best planes of the benzene and pyrrolidine rings is 62.6 (1) degrees . The crystal packing features inter-molecular N-H?F hydrogen bonds. PMID- 22058902 TI - 2-(4-Methyl-phen-yl)-1-phenyl-sulfonyl-3-nitro-1,2-dihydro-quinoline. AB - In the title compound, C(22)H(18)N(2)O(4)S, the dihedral angle between the phenyl sulfonyl ring and the methyl-phenyl ring is 67.78 (7) degrees . In the crystal, mol-ecules are linked by weak inter-molecular C-H?O inter-actions into a zigzag chain along the [101] direction. PMID- 22058903 TI - 3,4,5-Trihy-droxy-benzohydrazidium perchlorate-3,4,5-trihy-droxy-benzohydrazide water (1/1/1). AB - The crystal studied of the title compound, C(7)H(9)N(2)O(4) (+).ClO(4) ( ).C(7)H(8)N(2)O(4).H(2)O, was found to be a racemic twin with a 0.72 (18):0.28 (18) domain ratio. The hydrazidium group is close to planar, with an r.m.s deviation of 0.105 A; the hydrazide group deviates more from planarity, with an r.m.s deviation of 0.174 A. In the crystal, the hydrazidium cation, hydrazide mol ecule, perchlorate anions and water mol-ecules are linked through O-H?O, N-H?O and C-H?O hydrogen bonds into a three-dimensional supra-molecular network. In addition, the benzene rings of the hydrazidium and hydrazide units are connected via pi-pi inter-actions into infinite chains along the c axis; the centroid centroid distances are 3.486 (3) and 3.559 (3) A. PMID- 22058904 TI - rac-2-{[1-(1-Adamant-yl)eth-yl]imino-meth-yl}-5-meth-oxy-phenol. AB - A novel Schiff base compound, C(20)H(27)NO(2), was obtained by a condensation of rimantadine and 2-hy-droxy-4-meth-oxy-benzaldehyde. An intra-molecular O-H?N hydrogen bond supports the phenol-imine tautomeric form. The adamantane and imino methyl-4-meth-oxy-phenol units are arranged in a folded conformation [C-N-C-C torsion angle = 110.9 (3) degrees ]. In the crystal, highly hydro-phobic adamantane moieties are inserted between the imino-methyl-4-meth-oxy-phenol units in a sandwich-like arrangement along the c axis. PMID- 22058905 TI - A second monoclinic polymorph of 1-benzyl-N-methyl-1H-pyrrole-2-carboxamide. AB - In the title compound, C(13)H(14)N(2)O, the N(pyrrole)-C(H(2))-C-C torsion angle is -7.7 (3) degrees and the dihedral angle between the pyrrole and benzene rings is 83.6 (2) degrees . In the crystal, inter-molecular N-H?O hydrogen bonds link the mol-ecules into chains extending along the c axis. We have previously reported another polymorphic form of this title compound, which has the same space group with different cell parameters: a = 9.8285 (18) A, b = 23.588 (4) A, c = 9.9230 (17) A, beta = 90.107 (3) degrees , Z = 8 and V = 2300.5 (7) A(3) [Zeng et al. (2010 ?). Acta Cryst. E66, o2051]. PMID- 22058906 TI - 2-[(3-Propyl-sulfanyl-5-p-tolyl-4H-1,2,4-triazol-4-yl)imino-meth-yl]phenol. AB - In the title mol-ecule, C(19)H(20)N(4)OS, the two benzene rings form dihedral angles of 16.2 (1) and 12.0 (1) degrees , respectively, with the central triazole ring. In the crystal, inter-molecular O-H?N hydrogen bonds link mol-ecules into chains in the [010] direction. PMID- 22058907 TI - Bis[N-cyclohexyl-1-(2-{1-[(cyclohexyl-amino)carbonyl]cyclohexyl}-3,5-dioxo-1,2 oxazolidin-4-yl)cyclopentanecarbox-amide] monohydrate. AB - The reaction of cyclo-hexyl isocyanide and alkyl-idene Meldrum's acid (systematic name 2,2-dimethyl-1,3-dioxane-4,6-dione) in the presence of cyclo-hexyl ketoxime and dichloro-methane as solvent resulted in the title compound, 2C(28)H(43)N(3)O(5).H(2)O. One methyl-ene group of the cyclo-pentane ring was found to be disordered and was refined with occupancies 0.75:0.25. Intra molecular N-H?O hydrogen bonds occur. The crystal structure is stabilized by inter-molecular N-H?O and O-H?O hydrogen bonds. PMID- 22058908 TI - The 1:1 adduct of caffeine and 2-(1,3-dioxoisoindolin-2-yl)acetic acid. AB - IN THE CRYSTAL STRUCTURE OF THE TITLE ADDUCT [SYSTEMATIC NAME: 2-(1,3 dioxoisoindolin-2-yl)acetic acid-1,3,7-trimethyl-1,2,3,6-tetra-hydro-7H-purine 2,6-dione (1/1)], C(8)H(10)N(4)O(2).C(10)H(7)NO(4), the components are linked by an O-H?N hydrogen-bond and no proton transfer occurs. PMID- 22058909 TI - N,N'-(Ethane-1,2-di-yl)bis-(4-chloro-benzene-sulfonamide). AB - The title mol-ecule, C(14)H(14)Cl(2)N(2)O(4)S(2), lies on an inversion center. The mol-ecule is twisted in the region of the sulfonamide group with a C-S-N-C torsion angle of -67.49 (16) degrees . In the crystal, mol-ecules are connected via inter-molecular N-H?O and weak C-H?O hydrogen bonds, forming layers parallel to (100). PMID- 22058910 TI - 2-(5,6-Dihydro-benzimidazo[1,2-c]quinazolin-6-yl)phenol. AB - The asymmetric unit of the title compound, C(20)H(15)N(3)O, contains two independent mol-ecules, each of which is disordered over two sets of sites corresponding to a rotation of approximately 180 degrees of the dihydro benzimidazoquinazoline moiety, with refined site occupancies of 0.7479 (13) and 0.2521 (12) for both mol-ecules. The pyrimidine rings are in sofa conformations. In one mol-ecule, the hy-droxy-substituted benzene ring forms dihedral angles of 83.9 (3) and 82.4 (4) degrees for the major and minor components, respectively, with the mean plane of the benzimidazole ring system. The corres-ponding dihedral angles in the other mol-ecule are 88.31 (14) and 85.8 (6) degrees . In the crystal, mol-ecules are linked via inter-molecular O-H?N and N-H..O hydrogen bonds into chains along [100]. PMID- 22058911 TI - 4-[(4-Meth-oxy-benzene-sulfonamido)-meth-yl]cyclo-hexane-1-carb-oxy-lic acid. AB - In the title compound, C(15)H(21)NO(5)S, two crystallographically independent mol ecules are linked into a dimer by a pair of N-H?O hydrogen bonds, forming an R(2) (2)(8) ring motif. In the crystal, mol-ecules are further linked by inter molecular O-H?O hydrogen bonds into a two-dimensional network parallel to (012). Additional stabilization is provided by weak inter-molecular C-H?O hydrogen bonds. PMID- 22058912 TI - A centrosymmetric monoclinic polymorph of N,N-bis-(pyridin-3-yl-methyl idene)benzene-1,4-diamine. AB - The complete molecule of the title compound, C(18)H(14)N(4), is generated by the application of a centre of inversion. The dihedral angle between the central benzene ring and the pyridine ring is 31.88 (7) degrees . In the crystal, mol ecules are stacked in columns along the c axis and several inter-molecular pi-pi inter-actions are present between the six-membered rings, the shortest centroid centroid distance being 3.937 (2) A. The structure reported herein represents a centrosymmetric polymorph of the previously reported non-centrosymmetric (P2(1)) form [Kim et al. (2005 ?). Bull. Korean Chem. Soc.26, 892-898]. PMID- 22058913 TI - 2-[(4-Chloro-benzyl-idene)amino]-4,5,6,7-tetra-hydro-1-benzothio-phene-3 carbonitrile. AB - In the title compound, C(16)H(13)ClN(2)S, the dihedral angle between the 4-chloro benzaldehyde moiety and the heterocyclic five-membered ring is 7.21 (17) degrees . In the crystal, mol-ecules are linked by weak C-H?pi inter-actions, generating [100] chains. PMID- 22058914 TI - 5-(4-Bromo-2-nitro-phen-yl)-1,3,4-thia-diazol-2-amine. AB - The title compound, C(8)H(5)BrN(4)O(2)S, was synthesized by the reaction of 4 bromo-2-nitro-benzoic acid with thio-semi-carbazide. The dihedral angle between the thia-diazole and benzene rings is 40.5 (2) degrees . In the crystal, the strongest N-H?N inter-molecular hydrogen bond, between the amine group and one thia-diazole N atom, forms centrosymmetric dimers. The other amine H atom extends the supra-molecular network, forming an N-H?N contact with the other thia-diazole N atom. PMID- 22058915 TI - 4,4'-Diiodo-2,2'-[(3aR,7aR)-2,3,3a,4,5,6,7,7a-octa-hydro-1H-1,3-benzimidazole-1,3 di-yl)bis-(methyl-ene)]diphenol. AB - In the crystal structure of the title compound, C(21)H(24)I(2)N(2)O(2), the two N atoms of the imidazolidine moiety are linked to the hy-droxy groups by intra molecular O-H?N hydrogen-bonding inter-actions. The cyclo-hexane ring adopts a chair conformation and the heterocyclic ring to which it is fused has a twisted envelope conformation. PMID- 22058916 TI - 4,4'-Dibromo-2,2'-[octane-1,8-diylbis(nitrilo-methanylyl-idene)]diphenol. AB - The title compound, C(22)H(26)Br(2)N(2)O(2), has a centre of inversion that is located in the middle of the octyl chain; the chain displays an extended zigzag conformation. A short intra-molecular O-H?N hydrogen bond occurs. PMID- 22058917 TI - N-(2,6-Dimethyl-phen-yl)-2,4-dimethyl-benzene-sulfonamide. AB - Mol-ecules of the title compound, C(16)H(19)NO(2)S, are bent at the S atom with a C-SO(2)-NH-C torsion angle of -60.0 (2) degrees . The dihedral angle between the phenyl-sulfonyl and aniline rings is 41.7 (1) degrees . In the crystal, mol ecules are packed into centrosymmetric dimers through pairs of N-H?O(S) hydrogen bonds. PMID- 22058918 TI - 2-(1,3-Benzothia-zol-2-yl)-6-eth-oxy-phenol. AB - In the title compound, C(15)H(13)NO(2)S, the benzothia-zole unit is essentially planar [maximum deviation = -0.0099 (5) A for the S atom] and is oriented at a dihedral angle of 4.8 (5) degrees with respect to the benzene ring. An intra molecular O-H?N hydrogen bond generates an S(6) ring motif. The crystal packing is stabilized by C-H?pi inter-actions. PMID- 22058919 TI - rac-cis-Cyclo-hexane-1,2-dicarb-oxy-lic acid-isoquinoline (1/1). AB - In the crystal structure of the title mol-ecular adduct, C(9)H(7)N.C(8)H(12)O(4), the two species are -linked through a carb-oxy-lic acid-isoquinoline O-H?N hydrogen bond. These mol-ecular pairs then inter-associate through the second acid group of the cis-cyclo-hexane-1,2-dicarb-oxy-lic acid molecules, forming a classic centrosymmetric cyclic head-to-head carb-oxy-lic acid-carboxyl O-H?O hydrogen-bonding association [graph-set R(2) (2)(8)], giving a zero-dimensional (cluster) structure, consisting of two of each species. PMID- 22058920 TI - 3-Cyclo-hexyl-sulfonyl-2-methyl-5-propyl-1-benzofuran. AB - In the title compound, C(18)H(24)O(3)S, the cyclo-hexyl ring adopts a chair conformation. In the crystal, mol-ecules are linked through weak inter-molecular C-H?O hydrogen bonds and C-H?pi inter-actions. In the propyl group, one C atom is disordered over two sites with site-occupancy factors of 0.546 (8) and 0.454 (8). PMID- 22058921 TI - (S)-(-)-1-Phenyl-ethanaminium 4-(4,4-di-fluoro-1,3,5,7-tetra-methyl-3a,4a-diaza-4 borata-s-indacen-8-yl)benzoate. AB - The title compound, C(8)H(12)N(+).C(20)H(18)BF(2)N(2)O(2) (-), crystallizes with a significant amount of void space [4.0 (5)%] in the unit cell. The structure displays N-H?O hydrogen bonding between the components. The plane formed by the benzoic acid moiety of the BODIPY-CO(2) (-) is twisted by 80.71 (6) degrees relative to the plane formed by the ring C and N atoms of the tetramethyldipyrrin portion of the molecule. PMID- 22058922 TI - (Z)-(1,2-Dichloro-vin-yl)diphenyl-phosphine oxide. AB - The title compound, C(14)H(11)Cl(2)OP, was synthesized by the reaction of diphenyl-phosphine oxide with 1,2-dichloro-ethyne under CuI catalysis. The reaction provided the Z isomer regioselectively. Two O-P-C bond angles [114.3 (1) and 112.5 (1) degrees ] are significantly larger than the C-P-C [107.7 (1), 105.6 (1) and 106.6 (1) degrees ] and another O-P-C angle [109.5 (1) degrees ], indicating significant distortion of the tetra-hedral configuration of the P atom. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds into centrosymmetric dimers, which are connected by further C-H?O inter-actions into chains along [101]. PMID- 22058923 TI - Diethyl 1-benzyl-2,2-dioxo-4-phenyl-3,4,6,7,8,8a-hexa-hydro-1H-pyrrolo-[2,1 c][1,4]thia-zine-1,3-dicarboxyl-ate. AB - In the title compound, C(26)H(31)NO(6)S, the five-membered pyrrolidine ring adopts an envelope conformation and the six-membered thia-zine ring is in a distorted chair conformation. The crystal packing is stabilized through an inter molecular C-H?O inter-action, generating inversion-related R(2) (2)(10) ring motifs. PMID- 22058924 TI - 2-Oxochromen-4-yl 4-(dimethyl-amino)-benzoate. AB - In the title mol-ecule, C(18)H(15)NO(4), the benzoate ring is oriented at a dihedral angle of 43.43 (6) degrees with respect to the planar [maximum deviation = 0.038 (2) A] chromene ring. The crystal structure features R(2) (2)(12) centrosymetric dimers formed via C-H?O inter-actions and these dimeric aggregates are connected by C-H?pi inter-actions. PMID- 22058925 TI - 2,5-Dimethyl-1,3-dinitro-benzene. AB - The title compound, C(8)H(8)N(2)O(4), was prepared via the nitration of p-xylene. The mol-ecules are stacked along the c axis in an antiparallel manner. The two nitro groups are rotated relative to the benzene ring with dihedral angles of 44.50 (7) and 31.67 (8) degrees . The tilt of the nitro groups allows the formation of C-H?O inter-actions between the ring C-H and nitro groups of adjacent mol-ecules creating puckered sheets perpendicular to the c axis. The H atoms of the methyl group in the 5-position are disordered (60 degrees rotation) with an occupancy of 0.616 (19) for the major component. The crystal was found to be a non-merohedral twin with a twin law [-1 -0.002 0.005, 0.00031 -1 0.002, 0.118 -0.007 1] corresponding to a rotation of 180 degrees about the reciprocal axis (001) and refined to give a minor component fraction of 0.320 (2). PMID- 22058926 TI - N,N'-Bis(3-chloro-phen-yl)malonamide. AB - The asymmetric unit of the title compound, C(15)H(12)Cl(2)N(2)O(2), contains two independent mol-ecules. In both independent mol-ecules, the N-H bond in one of the amide fragments is anti to the meta-chloro group of the adjacent benzene ring and that in the other amide group is syn to the other meta-chloro group. Furthermore, in both mol-ecules, each amide group is almost coplanar with the adjacent phenyl ring, making dihedral angles of 10.5 (2) and 8.7 (2) degrees in one molecule and 9.0 (2) and 9.6 (2) degrees in the other. The planes of the amide groups are inclined at dihedral angles of 83.4 (1) and 87.4 (1) degrees in the two mol-ecules. In the crystal, mol-ecules are linked into a chain by inter molecular N-H?O hydrogen bonds. PMID- 22058927 TI - 1,2-Bis{[3,5-bis-(2,6-diisopropyl-phen-yl)phen-yl]imino}-acenaphthene toluene monosolvate. AB - In the title compound, C(72)H(80)N(2).C(7)H(8), the acenaphthene ring system is essentially planar, with a maximum deviation of 0.041 (3) A. The benzene rings bonded to the the N atoms are essentially parallel, forming a dihedral angle of 0.80 (11) degrees , and these rings form dihedral angles of 87.49 (9) and 88.25 (10) degrees with the mean plane of the acenaphthene ring system. The methyl C atoms of three of the isopropyl groups are disordered of two sets of sites of equal occupancy. PMID- 22058928 TI - N,N'-Bis[3,5-bis-(2,6-diisopropyl-phen-yl)phen-yl]butane-2,3-diimine. AB - The title mol-ecule, C(64)H(80)N(2), lies on an inversion center wherein the central butane-diimine fragment [N=C(Me)-C(Me)=N] is essentially planar [maximum deviation = 0.002 (2) A] and its mean plane forms a dihedral of 70.88 (10) degrees with the attached benzene ring. In the symmetry-unique part of the mol ecule, the dihedral angles between the benzene ring bonded to the N atom and the other two benzene rings are 89.61 (6) and 82.77 (6) degrees . PMID- 22058929 TI - 1,4-Bis(1H-benzimidazol-1-yl)benzene. AB - In the title compound, C(20)H(14)N(4), the dihedral angles between the central benzene ring and the pendant benzimidazole ring systems are 46.60 (15) and 47.89 (16) degrees . The dihedral angle between the benzimidazole ring systems is 85.62 (12) degrees and the N atoms lie to the same side of the mol-ecule. In the crystal, mol-ecules are linked by C-H?N inter-actions and weak aromatic pi-pi stacking [shortest centroid-centroid separation = 3.770 (2) A] is observed. PMID- 22058930 TI - (E)-1-(2-Hy-droxy-phen-yl)-3-(2,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one. AB - In the title chalcone derivative, C(18)H(18)O(5), the dihedral angle between the hy-droxy-substituted benzene ring and the trimeth-oxy-substituted benzene ring is 16.3 (1) degrees . The three meth-oxy groups are essentially coplanar with the benzene ring to which they are attached, with an r.m.s. deviation of 0.0208 A. An intra-molecular O-H?O hydrogen bond generates an S(6) ring motif. In the crystal, weak C-H?O inter-actions link mol-ecules into helical chains along the b axis. These chains are connected into sheets parallel to the bc plane by further weak C H?O inter-actions. PMID- 22058931 TI - Caffeinium bis-ulfate monohydrate. AB - IN THE TITLE COMPOUND (SYSTEMATIC NAME: 1,3,7-trimethyl-2,6-dioxo-7H-purin-9-ium hydrogen sulfate monohydrate), C(8)H(11)N(4)O(2) (+).HSO(4) (-).H(2)O, the crystal packing is stabilized through N-H?O and O-H?O hydrogen bonds. PMID- 22058932 TI - 6-(4-Chloro-phen-yl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-carbaldehyde. AB - The 4-chloro-phenyl residue in the title compound, C(20)H(16)ClNO, is oriented at a dihedral angle of 53.6 (3) degrees towards the phenyl ring and 42.0 (9) degrees towards the pyrrole ring of the pyrrolizine template. The phenyl ring is oriented at a dihedral angle of 45.4 (4) degrees towards the pyrrole ring. PMID- 22058933 TI - 4,6-Dihy-droxy-4,6-dimethyl-1,3-diazinane-2-thione. AB - In the title compound, C(6)H(12)N(2)O(2)S, the heterocyclic ring has a sofa conformation. The mol-ecular conformation is stabilized by an intra-molecular O H?O hydrogen-bond inter-action with graph-set motif S(6). In the crystal, mol ecules are linked by O-H?S, N-H?S and N-H?O hydrogen-bond inter-actions, forming an extended two-dimensional framework parallel to the ac plane. PMID- 22058934 TI - Di-n-butyl 4,4'-dihy-droxy-3,3'-{[(3aRS,7aRS)-2,3,3a,4,5,6,7,7a-octa-hydro-1H-1,3 benzimidazole-1,3-di-yl]bis-(methyl-ene)}dibenzoate. AB - The complete molecule of the title compound, C(31)H(42)N(2)O(6), is generated by crystallographic twofold symmetry, with one C atom lying on the axis. The dihedral angle between the aromatic rings is 57.03 (6) degrees . The central heterocyclic ring adopts a half-chair conformation. The mol-ecular conformation is stabilized by two intra-molecular O-H?N hydrogen bonds with the N atoms of the heterocyclic ring as the acceptors. In the crystal, mol-ecules are linked into chains along the c axis by non-classical C-H?O hydrogen bonds. PMID- 22058935 TI - (E)-3-[3,4-Bis(meth-oxy-methoxy)phen-yl]-1-(7-hy-droxy-5-meth-oxy-2,2-dimethyl chroman-8-yl)prop-2-en-1-one. AB - The reaction of 5,6-(2,2-dimethyl-chroman-yl)-2-hy-droxy-4-meth-oxy-acetophenone and 3,4-bis-(meth-oxy-meth-yloxy)benzaldehyde affords the intense orange title chalcone derivative, C(25)H(30)O(8). The two benzene rings are connected through a -C(=O)-CH=CH- (propenone) unit, which is in an E conformation; the ring with the hy-droxy substitutent is aligned at 19.5 (2) degrees with respect to this unit, whereas the ring with the meth-oxy-meth-yloxy substituent is aligned at 9.3 (3) degrees . The dihedral angle between the rings is 19.38 (10) degrees . The hy droxy group engages in an intra-molecular O-H?O hydrogen bond with the carbonyl O atom of the propenone unit, generating an S(5) ring. PMID- 22058936 TI - (E)-3-(2H-1,3-Benzodioxol-5-yl)-1-(7-hy-droxy-5-meth-oxy-2,2-dimethyl-chroman-8 yl)prop-2-en-1-one. AB - The reaction of 5,6-(2,2-dimethyl-chromane)-2-hy-droxy-4-meth-oxy-acetophenone and 3,4-methlene-dioxy-benzaldehyde affords the title chalcone derivative, C(22)H(22)O(6). The two benzene rings are connected through a -C(=O)-CH=CH- (propenone) unit, which is in an E conformation; the ring with the hy-droxy substitutent is aligned at 6.2 (1) degrees with respect to this unit, whereas the ring with the methyl-enedi-oxy substituent is aligned at 8.2 (1) degrees . The dihdral angle between the rings is 14.32 (7) degrees . The hy-droxy group engages in an intra-molecular hydrogen bond with the carbonyl O atom of the propenone unit, generating an S(5) ring. PMID- 22058937 TI - Diethyl 2,5-bis-[(1E)-(1H-pyrrol-2-yl-methyl-idene)amino]-thio-phene-3,4 dicarboxyl-ate. AB - In the crystal structure of the title compound, C(20)H(20)N(4)O(4)S, the azomethine group adopt E conformations. The pyrrole units are twisted by 10.31 (4) and 18.90 (5) degrees with respect to the central thio-phene ring. The three dimensional network is close packed and involves N-H?O, N-H?N, C-H?N and C-H?O hydrogen bonding. PMID- 22058938 TI - N'-[(E)-2-Hy-droxy-3,5-diiodo-benzyl-idene]pyridine-3-carbohydrazide. AB - In the title compound, C(13)H(9)I(2)N(3)O(2), the dihedral angle between the two aromatic rings is 10.5 (2) degrees . The mol-ecule displays a trans configuration with respect to the C=N bond. An intra-molecular O-H?N hydrogen bond occurs. The crystal packing is stabilized by N-H?O and C-H?O hydrogen bonds. PMID- 22058939 TI - N-[(E)-1,3-Benzodioxol-5-yl-methyl-idene]-3,4-dimethyl-1,2-oxazol-5-amine. AB - In the title compound, C(13)H(12)N(2)O(3), the dihedral angle between the aromatic rings is 7.94 (12) degrees . In the crystal, inversion dimers linked by pairs of C-H?O hydrogen bonds generate R(2) (2)(6) loops. Weak pi-pi [centroid centroid separations = 3.7480 (13) and 3.9047 (13) A] and C-H?pi inter-actions help to consolidate the packing. PMID- 22058940 TI - (E)-2-(4-Bromo-benzyl-idene)indan-1-one. AB - In the title compound, C(16)H(11)BrO, the dihydro-indene ring system is approximately planar, with a maximum deviation of 0.008 (2) A. The mean plane of this ring system forms a dihedral angle of 3.73 (11) degrees , with the bromo substituted benzene ring. In the crystal, weak inter-molecular C-H?O hydrogen bonds link the mol-ecules into sheets parallel to the ab plane and further stabilization is provided by weak C-H?pi inter-actions involving the bromo substituted benzene rings. PMID- 22058941 TI - 2-Phenyl-ethyl 1-thio-beta-d-galactopyran-oside hemihydrate. AB - The title compound, C(14)H(20)O(5)S.0.5H(2)O, crystallizes with two organic mol ecules and a solvent water mol-ecule in the asymmetric unit. In both mol-ecules, the hexa-pyranosyl rings adopt a slightly distorted chair conformation ((5)C(2)) with four substituents in equatorial positions and one substituent in an axial position. The main difference between the organic mol-ecules is the dihedral angle between the phenyl ring and the best plane defined by the O-C(1)-C(2)-C(3) atoms (r.m.s deviations = 0.003 and 0.043 A) of the hexa-pyranosyl rings [47.4 (4) and 86.5 (4) degrees ]. In the asymmetric unit, mol-ecules are linked by two strong O-H?O hydrogen bonds. In the crystal, the components are linked by a total of 10 distinct O-H?O hydrogen bonds, resulting in the formation of a two dimensional network parallel to the ab plane. PMID- 22058942 TI - 3-(4-Chloro-phen-yl)quinazolin-4(3H)-one. AB - In the title compound, C(14)H(9)ClN(2)O, the quinazoline unit is essentially planar, with a mean deviation from the least-squares plane defined by the ten constituent ring atoms of 0.027 (2) A. The dihedral angle between the mean plane of the quinazoline ring system and the 4-chloro-phenyl ring is 44.63 (5) degrees . In the crystal, mol-ecules are linked by inter-molecular C-H?N and C-H?O hydrogen bonds, forming infinite chains of alternating R(2) (2)(6) dimers and R(2) (2)(14) ring motifs. PMID- 22058943 TI - Ethyl (2E)-2-cyano-3-(1-methyl-1H-pyrrol-2-yl)prop-2-enoate. AB - The 15 non-H atoms of the title compound, C(11)H(12)N(2)O(2), are approximately coplanar, the r.m.s. deviation being 0.145 A. The major deviation from coplanarity is seen in a twist between the ethene (E configuration) and pyrrole rings [C-C-N-C torsion angle = -8.26 (18) degrees ]. The carbonyl O and cyano N atoms are syn to each other. In the crystal, supra-molecular linear tapes linked by C-H?O and C-H?N inter-actions are further connected by C-H?pi(pyrrole) inter actions. PMID- 22058944 TI - Ethyl 5-((1E)-1-{(E)-2-[1-(4-eth-oxy-carbonyl-3-methyl-1,2-oxazol-5-yl)ethyl idene]hydrazin-1-yl-idene}eth-yl)-3-methyl-1,2-oxazole-4-carboxyl-ate. AB - The complete mol-ecule of the title compound, C(18)H(22)N(4)O(6), is generated by the application of a twofold axis of symmetry. Twists are evident in the mol ecule, i.e. between each -C=N-N group and the adjacent oxazole ring [dihedral angle = 46.08 (12) degrees ] and between the latter and attached ester group [excluding the terminal methyl group; dihedral angle = 24.4 (7) degrees ]. In the crystal, C-H?O and pi-pi [3.5990 (11) A] contacts connect mol-ecules into supra-molecular arrays in the ac plane. These stack along the b axis, being connected by weak pi-pi [3.3903 (11) A] inter-actions. PMID- 22058945 TI - N'-[(1E,2E)-1-(2-Phenyl-hydrazin-1-yl-idene)-1-(phenyl-sulfon-yl)propan-2-yl idene]benzohydrazide. AB - The configuration about each C=N bond in the title compound, C(22)H(20)N(4)O(3)S, is E. While to a first approximation the phenyl-hydrazin-1-yl-idene and benzohydrazide residues are coplanar, in part due to the presence of an intra molecular N-H?N hydrogen bond, significant twists are evident in the orientations of the hydrazine [N-N-C-C torsion angle = -170.74 (11) degrees ] and benzoyl benzene [N-C-C-C = -21.72 (18) degrees ] rings. The sulfonyl benzene ring occupies a position almost normal to the rest of the mol-ecule [C-S-C-N = -92.28 (10) degrees ]. Centrosymmetric aggregates mediated by pairs of hydrazide sulfonyl N-H?O hydrogen bonds are the predominant packing motif in the crystal. These are connected into linear supra-molecular chains via C-H?O inter-actions which are, in turn, linked into layers in the ac plane via C-H?pi inter-actions. Connections between layers along the b-axis direction are of the pi-pi type and occur between centrosymmetrically related hydrazine-bound benzene rings [centroid centroid separation = 3.7425 (9) A]. PMID- 22058946 TI - 2-{(E)-[(4-Methyl-phen-yl)imino]-meth-yl}-4-nitro-phenol-2-{(E)-[(4-methyl-phen yl)iminio]meth-yl}-4-nitro-phenolate (0.60/0.40). AB - The crystal of the title compound, 0.6C(14)H(12)N(2)O(3).0.4C(14)H(12)N(2)O(3), contains a mixture of its neutral (OH containing) and zwitterionic (NH containing) forms, in a 0.60 (4):0.40 (4) ratio. The former generates an S(6) loop via an intra-molecular O-H?N hydrogen bond and the latter generates an S(6) loop via an N-H?O hydro-gren bond. The aromatic rings are oriented at a dihedral angle of 42.52 (10) degrees . In the crystal, C-H?pi inter-actions occur and aromatic pi-pi stacking inter-actions [centroid-centroid separations = 3.7106 (12) and 3.9177 (13) A] consolidate the packing. PMID- 22058947 TI - A 1:1 co-crystal of the herbicide triflusulfuron-methyl and its degradation product triazine amine. AB - The herbicide triflusulfuron-methyl (systematic name: methyl 2-{[4-dimethyl-amino 6-(2,2,2-trifluoro-eth-oxy)-1,3,5-triazin-2-yl]carbamoylsulfamo-yl}-3-methyl benzoate) and its degradation product triazine amine [systematic name: 2-amino-4 dimethyl-amino-6-(2,2,2-trifluoro-eth-oxy)-1,3,5-triazine] form a triclinic 1:1 co-crystal of the title compound, C(7)H(10)F(3)N(5)O.C(17)H(19)F(3)N(6)O(6)S, in which its two components are connected via a pair of complementary N-H?N hydrogen bonds, similar to the monoclinic crystal structure of the parent compound triflusulfuron-methyl [Mereiter (2011 ?). Acta Cryst. E67, o1778-o1779] in which a pair of mol-ecules related by a twofold axis are linked by two N-H?N bonds. The triflusulfuron-methyl mol-ecules of both crystal structures are similar in geometric parameters and conformation, which is due to stiffening by a short intra-molecular N-H?N bond [N?N = 2.620 (4) A] and an intra-molecular dipole dipole inter-action between the sulfamide and the carboxyl moieties, with O(s)?C(c) = 2.802 (5) A and O(c)?N(s) = 2.846 (4) A. Inter-molecular N-H?O hydrogen bonds and slipped pi-pi stacking inter-actions between the diamino triazine moieties [perpendicular distances of 3.25 A within hydrogen-bonded tetra mers and 3.27 A between adjacent tetra-mers] link the two constituents of the co crystal into columns parallel to the a axis. An intra-molecular C-H?O hydrogen bond occurs in the triflusulfuron-methyl mol-ecule and inter-molecular C-H?O inter-actions between triflusulfuron-methyl mol-ecules occur in the crystal structure. In the triflusulfuron-methyl molecule the dihedral angle between the least-squares planes of the two rings is 75.8 (1) degrees . In the triazine molecule, the CF(3) group is partly orientationally disordered. PMID- 22058948 TI - 2,3,6,3',4'-Penta-O-acetyl-4,1',6'-tri-chloro-4,1',6'-tride-oxy-sucrose. AB - In the title compound, C(22)H(29)Cl(3)O(13), the glucopyran ring exists in the chair conformation while the glucofuran ring adopts an envelope conformation. Intra-molecular C-H?O hydrogen bonds occur. In the crystal, adjacent mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds. PMID- 22058949 TI - 2-[(tert-But-oxy-carbonyl-amino)-oxy]acetic acid. AB - The title compound, C(7)H(13)NO(5), was prepared by the condensation of O-(carb oxy-meth-yl)hydroxyl-amine and (Boc)(2)O (Boc = but-oxy-carbon-yl).In the crystal, mol-ecules are linked by weak inter-molecular N-H?O hydrogen bonds. PMID- 22058950 TI - (2S)-3-(1H-Indol-3-yl)-2-(4-methyl-benzene-sulfonamido)-propionic acid monohydrate. AB - In the title compound, C(18)H(18)N(2)O(4)S.H(2)O, the indole and toluene ring systems are oriented at a dihedral angle of 84.51 (9) degrees . In the crystal, the components are linked by N-H?O, O-H?O, C-H?O and N-H?pi inter-actions. These include a short link from the alpha-C atom of the amino acid fragment. PMID- 22058951 TI - (E)-1-(2-Iodo-phen-yl)-2-phenyl-diazene. AB - The mol-ecule of the title compound, C(12)H(9)IN(2), is approximately planar [maximum deviation = 0.020 (5) A] with a trans arrangement of the groups around the N=N double bond. This double bond is rotated away from the iodine substiuent. PMID- 22058952 TI - 3-(3-Fluoro-phenyl-sulfin-yl)-2,4,5,6-tetra-methyl-1-benzofuran. AB - In the title compound, C(18)H(17)FO(2)S, the 3-fluoro-phenyl ring makes a dihedral angle of 78.60 (5) degrees with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds and weak inter-molecular C-S?pi [3.490 (2) A] inter-actions. PMID- 22058953 TI - 3-(3,4-Dimeth-oxy-phen-yl)-4-(2-meth-oxy-anilino)furan-2(5H)-one. AB - In the title compound, C(19)H(19)NO(5), the furan-one unit makes a dihedral angle of 30.93 (6) degrees with the benzene ring and a dihedral angle of 9.51 (6) degrees with the aniline ring. In the crystal, inter-molecular C-H?O hydrogen bonds and C-H?pi contacts link the mol-ecules into sheets. A weak intramolecular hydrogen bond is also observed. PMID- 22058954 TI - 3-(4-Bromo-phen-yl)-4-(4-hy-droxy-anilino)furan-2(5H)-one. AB - In the title compound, C(16)H(12)BrNO(3), the butyrolactone core adopts the furan 2(5H)-one structure and forms dihedral angles of 44.80 (17) and 65.73 (18) degrees with the bromo-benzene and phenol rings, respectively. In the crystal, N H?O and O-H?O hydrogen bonds link the mol-ecules, generating R(4) (3)(26) loops The edge-fused rings extend to form a chain running along the b-axis direction and C-H?pi contacts help to consolidate the packing. PMID- 22058955 TI - 1-Isobutyl-4-meth-oxy-1H-imidazo[4,5-c]quinoline. AB - In the title compound, C(15)H(17)N(3)O, the 1H-imidazo[4,5-c]quinoline ring system is approximately planar, with a maximum deviation of 0.036 (1) A. The C-N C-C torsion angles formed between this ring system and the isobutyl unit are 99.77 (16) and 79.71 (17) degrees . In the crystal, inter-molecular C-H?O hydrogen bonds link the mol-ecules into chains along the c axis. PMID- 22058956 TI - (E)-N-[(6-Bromo-pyridin-2-yl)methyl-idene]-4-methyl-aniline. AB - The title compound, C(13)H(11)BrN(2), a Schiff base obtained from 6-bromo picolinaldehyde and p-toluidine, has an E configuration about the C=N bond. The dihedral angle between the benzene and pyridine rings is 30.4 (1) degrees . PMID- 22058957 TI - Ethyl 4-chloro-2'-fluoro-3-hy-droxy-5-methyl-biphenyl-2-carboxyl-ate. AB - In the title compound, C(16)H(14)ClFO(3), the dihedral angle between the mean planes of the two benzene rings is 71.50 (5) degrees . Due to an intra-molecular O-H?O hydrogen bond between the hy-droxy group and the carbonyl O atom of the ethyl ester group, the ethyl ester group lies within the ring plane. The crystal structure is consolidated by inter-molecular C-H?O and C-H?F inter-actions. PMID- 22058958 TI - (E)-3-Hy-droxy-5,5-dimethyl-2-(3-phenyl-prop-2-en-1-yl)cyclo-hex-2-en-1-one. AB - Five of the atoms of the six-membered cyclo-hexene ring of the title compound, C(17)H(20)O(2), are essentially coplanar (r.m.s. deviation = 0.006 A), with the sixth (the dimethyl-methyl C atom) deviating from the mean plane of the five atoms by 0.610 (2) A. This plane is nearly perpendicular to the cinnamyl portion, the two planes being aligned at 85.1 (1) degrees . Two mol-ecules are linked by an O-H?O hydrogen bond about a center of inversion. The cyclo-hexene ring is disordered over two directly overlapping positions. As a result, the hy-droxy group and the keto O atom cannot be distinguished from one another. PMID- 22058959 TI - (E)-2-Bromo-benzaldehyde oxime. AB - The configuration of the C=N double bond of the title compound, C(7)H(6)BrNO, is E; the non-H atoms are approximately coplanar (r.m.s. deviation = 0.038 A). In the crystal, pairs of mol-ecules are linked by a pair of O-H?N hydrogen bonds about a center of inversion, generating hydrogen-bonded dimers. PMID- 22058960 TI - N,N-Bis(pyridin-3-ylmeth-yl)isophthalamide dihydrate. AB - The complete organic molecule in the title dihydrate, C(20)H(22)N(4)O(4), is generated by crystallographic twofold symmetry, with two C atoms lying on the rotation axis. The symmetry unique pyridine ring forms a dihedral angle of 83.16 (8) degrees with the central benzene ring. In the crystal, inter-molecular N H?O, O-H?N and O-H?O hydrogen bonds connect the components into a two-dimensional network lying parallel to (101). PMID- 22058961 TI - 2-{Hy-droxy[1-(4-meth-oxy-phen-yl)-4-oxo-3-phenyl-azetidin-2-yl]meth yl}acrylonitrile. AB - In the title compound, C(20)H(18)N(2)O(3), the beta-lactam ring is essentially planar, having a maximum deviation of 0.0291 (15) A for the N atom, and perpendicular to the phenyl ring [dihedral angle = 85.55 (11) degrees ]. The carbonitrile side chain is almost linear, the C-C-N angle being 176.8 (2) degrees . The crystal packing is stabilized by inter-molecular O-H?O and C-H?O inter actions. PMID- 22058962 TI - 5-Benzyl-5H-pyrido[3,2-b]indole. AB - The title compound, C(18)H(14)N(2), was prepared by twofold Pd-catalyzed aryl amination of a cyclic pyrido-benzo-iodo-lium salt. In the crystal, two mol-ecules of 9-benzyl-delta-carboline form centrosymmetrical dimers with distances of 3.651 (2) A between the centroids of the pyridine rings and 3.961 (2) A between the centroids of the pyrrole and pyridine rings. The phenyl rings point to the other mol-ecule in the dimer and the carboline core is essentially planar [maximum deviation of 0.027 (2) A]. PMID- 22058963 TI - 3-{1-[2-(2-Chloro-phen-yl)hydrazinyl-idene]-2,2,2-trifluoro-eth-yl}-7-diethyl amino-2H-chromen-2-one. AB - The title compound, C(21)H(19)ClF(3)N(3)O(2), has a structure related to other coumarin derivatives that have been used as fluorescent probes of metal ions. The dihedral angle between the coumarin ring system and the chlorobenzene ring is 42.99 (9) degrees . Intra-molecular hydrogen bonding occurs via N-H?O and N-H?Cl inter-actions, generating S(7) and S(5) rings, respectively. The crystal packing is stabilized by weak C-H?O hydrogen bonds. PMID- 22058964 TI - 8-(2-Hy-droxy-phen-yl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione. AB - The title compound, C(13)H(12)N(4)O(3), is an imidazole derivative featuring an annealed purine ring system. The benzimidazole-inspired moiety is essentially planar (r.m.s. of all fitted non-H atoms = 0.0205 A). An intra-molecular O-H?N hydrogen bond occurs. In the crystal, inter-molecular N-H?O and C-H?O hydrogen bonds are observed, which connect the mol-ecules into chains along [110]. The shortest centroid-centroid distance between two aromatic systems is 3.7771 (11) A. PMID- 22058965 TI - (4-Methyl-phen-yl)[2-(thio-phen-2-ylcarbon-yl)phen-yl]methanone. AB - The crystal studied of the title compound, C(19)H(14)O(2)S, was an inversion twin with a 0.7 (1):0.3 (1) domain ratio. The central benzene ring makes dihedral angles of 63.31 (9) and 60.86 (9) degrees , respectively, with the 4-methyl phenyl and thio-phene rings. In the crystal, mol-ecules are linked by weak inter molecular C-H?O hydrogen bonds and S?pi [3.609 (3) A] inter-actions. PMID- 22058966 TI - 2,4-Dioxo-1-(prop-2-yn-yl)-1,2,3,4-tetra-hydro-pyrimidine-5-carbaldehyde. AB - In the crystal structure of the title compound, C(8)H(6)N(2)O(3), the mol-ecules are linked by a pairs of inter-molecular N-H?O hydrogen bonds, forming inversion dimers. The aldehyde group is in the same plane as the pyrimidine ring [with a maximum deviation of 0.083 (2) A for the O atom), and the linear propargyl group [C-C-C = 178.99 (19) degrees ] makes a dihedral angle of 74.36 (13) degrees with the ring. PMID- 22058967 TI - Tramadol hydro-chloride-benzoic acid (1/1). AB - In the cation of the title co-crystal salt {systematic name: [2-hydroxy-2-(3-meth oxy-phen-yl)cyclo-hexyl-meth-yl]dimethyl-aza-nium chloride-benzoic acid (1/1)}, C(16)H(31)NO(2) (+).Cl(-).C(7)H(6)O(2), the N atom is protonated and the six membered cyclo-hexane ring adopts a slightly distorted chair conformation. The dihedral angle between the mean planes of the benzene rings in the cation and the benzoic acid mol-ecule is 75.5 (9) degrees . The crystal packing is stabilized by weak inter-molecular O-H?Cl, N-H?Cl and C-H?pi inter-actions, forming a two dimensional chain network along the b axis. The benzoic acid mol-ecule is not involved in the usual head-to-tail dimer bonding, but instead is linked to the ammonium cation through mutual hydrogen-bonding inter-actions with the chloride anion. PMID- 22058968 TI - Ethyl 6-amino-8-(4-chloro-phen-yl)-9-nitro-2,3,4,8-tetra-hydro-pyrido[2,1 b][1,3]thia-zine-7-carboxyl-ate. AB - In the structure of the title compound, C(17)H(18)ClN(3)O(4)S, the thia-zinane ring displays a twist-boat conformation. The 1,4-dihydro-pyridine ring is approximately perpendicular to the benzene ring [dihedral angle = 88.3 (1) degrees ]. The mol-ecular conformation is stabilized by an intra-molecular N-H?O hydrogen bond. In the crystal, mol-ecules are linked by N-H?O inter-actions into a C(8) chain along [100]. PMID- 22058969 TI - (1E,4E)-1,5-Bis(thio-phen-3-yl)penta-1,4-dien-3-one. AB - The title compound, C(13)H(10)OS(2), exhibits twists between the central C(3)O and ethene residues [O-C-C-C torsion angles = -8.4 (3) and 11.8 (3) degrees ], and between the ethene and adjacent thio-phenyl residues [C-C-C-C torsion angles = -4.2 (3) and 10.5 (3) degrees ]. As a result, the mol-ecule is non-planar, the dihedral angle formed between the terminal thio-phenyl groups being 15.45 (10) degrees . The presence of C-H?O inter-actions involving the bifurcated carbonyl O atom leads to supra-molecular arrays in the ac plane. These are linked into a three-dimensional architecture by C-H?pi inter-actions involving both thio-phenyl residues. PMID- 22058970 TI - 1-Benzyl-2,5-diphenyl-3-tosylimidazol-idin-4-one. AB - In the title compound, C(29)H(26)N(2)O(3)S, the central imidazolidine ring adopts an envelope conformation with the N atom bearing the benzyl ring at the flap. The S atom has distorted tetra-hedral geometry. The benzyl and tosyl rings are oriented at a dihedral angle of 52.1 (1) degrees . The phenyl rings connected to the imidazolidine ring form a dihedral angle of 28.7 (1) degrees . PMID- 22058971 TI - 2-[(4-Chloro-phenyl)-amino-meth-yl]phenol. AB - In the title mol-ecule, C(13)H(12)ClNO, the two benzene rings are twisted from each other by a dihedral angle of 68.60 (8) degrees . In the crystal structure, the hy-droxy and amino H atoms are involved in inter-molecular hydrogen bonds, O H?N and N-H?O, respectively, resulting in R(4) (4)(8) loops about inversion centers. PMID- 22058972 TI - Naphthalen-1-aminium chloride. AB - In the crystal structure of the title compound, C(10)H(10)N(+).Cl(-), the two components are connected via N-H?Cl hydrogen bonds, forming a layer parallel to the bc plane. PMID- 22058973 TI - 1-(4-Chloro-benzo-yl)-3-(3-methyl-pyridin-2-yl)thio-urea. AB - The mol-ecule of the title compound, C(14)H(12)ClN(3)OS, consists of three approximately planar fragments: the central thio-urea group, the chloro-phenyl group and the picolyl (3-methyl-pyridin-2-yl) group with a maximum of 0.035 (2) degrees for an N atom from the mean square plane of the central thiourea group. The central fragment forms dihedral angles of 33.30 (8) and 76.78 (8) degrees with the chloro-phenyl and picolyl groups, respectively. With respect to the thio urea C-N bonds, the 4-chloro-benzoyl group is positioned trans to the thiono S atoms, whereas the picolyl group lies in a cis position to it. The mol-ecular conformation is stabilized by an intra-molecular N-H?O hydrogen bond. In the crystal, mol-ecules are linked by inter-molecular C-H?N hydrogen bonds, forming chains along the a axis. PMID- 22058974 TI - 1-Iodo-triptycene. AB - The title compound, C(20)H(13)I, is a halogenated derivative of triptycene. The mol-ecule shows crystallographic as well as non-crystallographic C(3) symmetry. The asymmetric unit comprises one third of the mol-ecule. Dispersive I?I contacts [I?I = 3.6389 (3) A] connect the mol-ecules into dimers. The shortest centroid centroid distance between two pi-systems is 3.8403 (12) A. PMID- 22058975 TI - 1-Phenyl-5-{[2-(trimethyl-sil-yl)eth-yl]sulfon-yl}-1H-tetra-zole. AB - The title compound, C(12)H(18)N(4)O(2)SSi, was synthesized to be employed in a Julia-Kocienski olefination. In the mol-ecule, the dihedral angle between the phenyl ring and the tetra-zole ring is 41.50 (5) degrees . The significantly longer Si-C(methyl-ene) bond [1.8786 (13) A] and the shortened adjacent C-C bond [1.5172 (18) A], as well as the significant deviation of the corresponding Si-C-C angle [114.16 (9) degrees ] from the ideal tetra-hedral angle, can be attributed to the beta-effect of silicon. In the crystal, mol-ecules are held together by van der Waals inter-actions. PMID- 22058976 TI - 2,2'-Bis(meth-oxy-meth-oxy)-3-methyl-1,1'-binaphth-yl. AB - The title compound, C(25)H(24)O(4), a meth-oxy-methyl (MOM) bis-protected BINOL derivative containing a methyl substituent in position 3, is a key inter-mediate for the synthesis of a great variety of chiral auxiliaries. The planes of the naphthyl aromatic rings are at an angle of 70.74 (3) degrees . There are no conventional hydrogen bonds binding the mol-ecules. PMID- 22058977 TI - N,N'-(Propane-1,3-di-yl)bis-(p-toluene-sulfonamide). AB - The complete mol-ecule of the title compound, C(17)H(22)N(2)O(4)S(2), is generated by crystallographic twofold symmetry, with one C atom lying on the rotation axis. The dihedral angle between the benzene rings is 44.04 (7) degrees and the conformation of the central N-C-C-C group is gauche. In the crystal, mol ecules are linked by N-H?O hydrogen bonds, generating corrugated (010) sheets, and weak C-H?O inter-actions consolidate the packing. PMID- 22058978 TI - 5-[(E)-(2-Fluoro-benzyl-idene)amino]-2-hy-droxy-benzoic acid. AB - In the title compound, C(14)H(10)FNO(3), the dihedral angle between the two benzene rings is 32.66 (14) degrees . An S(6) ring motif is formed due to an intra-molecular O-H?O hydrogen bond between the hy-droxy and carbonyl groups. In the crystal, mol-ecules are consolidated into dimers with R(2) (2)(8) ring motifs by pairs of O-H?O hydrogen bonds. PMID- 22058979 TI - 2-(5,6-Dihydro-benzimidazo[1,2-c]quinazolin-6-yl)-5-methyl-phenol. AB - In the title compound, C(21)H(17)N(3)O, the imidazole ring is essentially planar, with a maximum deviation of 0.009 (1) A. The mol-ecule is disordered over two sites corresponding to a rotation of approximately 180 degrees with a refined occupancy ratio of 0.9180 (14):0.0820 (14). The central pyrim-idine ring makes dihedral angles of 5.02 (5), 3.97 (5) and 6.28 (5) degrees , respectively, with the planes of the imidazole and the terminal phenyl rings for the major component; the values for the minor component are 5.8 (7), 5.0 (6) and 8.5 (6) degrees , respectively. Part of the observed planarity is accounted for in terms of an intra-molecular N-H?O hydrogen bond. In the crystal, mol-ecules of the major component are connected by O-H?N hydrogen bonds, forming supra-molecular chains along the c axis. PMID- 22058980 TI - 2,4,6-Trimethyl-pyridinium 4-nitro-benzoate-4-nitro-benzoic acid (1/1). AB - The asymmetric unit of the title co-crystal, C(8)H(12)N(+).C(7)H(4)NO(4) ( ).C(7)H(5)NO(4), contains two cations, two anions and two neutral 4-nitro-benzoic acid mol-ecules. In the crystal, O-H?O, N-H?O and C-H?O hydrogen bonds connect the ions and mol-ecules, forming a three-dimensional network. PMID- 22058981 TI - 3,3'-Diphenyl-1,1'-(butane-1,4-di-yl)dithio-urea. AB - The asymmetric unit of the title compound, C(18)H(22)N(4)S(2), contains one half mol-ecule, the complete mol-ecule being generated by crystallographic inversion symmetry. The crystal structure features two inter-molecular N-H?S hydrogen bonding inter-actions, the first generating an infinite chain along the b axis and the second an infinite chain along the a axis, together forming an inter locking structure. PMID- 22058982 TI - 4'-[5-(4-Fluoro-phen-yl)pyridin-3-yl]-1'-methyl-dispiro-[indan-2,2'-pyrrolidine 3',2''-indan]-1,3,1''-trione. AB - In the title compound, C(32)H(23)FN(2)O(3), the pyrrolidine ring adopts an envelope conformation. The monoketo- and diketo-substituted five-membered rings are in envelope and half-chair conformations, respectively. The mol-ecular structure is stabilized by an intra-molecular C-H?O hydrogen bond, which generates an S(6) ring motif. In the crystal, mol-ecules are linked via inter molecular C-H?N and C-H?O hydrogen bonds into a three-dimensional network. The crystal structure is further consolidated by C-H?pi inter-actions. PMID- 22058983 TI - 4,10-Bis(pyridin-2-ylmeth-yl)-1,7-dithia-4,10-diazo-niacyclo-dodecane bis(perchlorate). AB - The asymmetric unit of the title compound C(20)H(30)N(4)S(2) (+). 2ClO(4) (-) comprises one macrocyclic cation and two perchlorate anions. In the cation, one of the protonated H atoms bound to the amide N atom is involved in an intra molecular N-H?N hydrogen bond. The O atoms in the two perchlorate anions are disordered over two sets of sites with occupancy ratios of 0.65 (3):0.35 (3) and 0.640 (15):0.360 (15). PMID- 22058984 TI - 5-Chloro-3-cyclo-hexyl-sulfinyl-2,7-dimethyl-1-benzofuran. AB - In the title compound, C(16)H(19)ClO(2)S, the cyclo-hexyl ring adopts a chair conformation and the aryl-sulfinyl unit is positioned equatorial relative to the cyclo-hexyl group. The least-squares plane through all six C atoms of the cyclo hexyl ring makes a dihedral angle of 74.80 (6) degrees with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked through inter molecular C-H?O hydrogen bonds. PMID- 22058985 TI - 9-(4-Chloro-phen-yl)-4a-hy-droxy-4,4a,5,6,9,9a-hexa-hydro-3H-xanthene-1,8(2H,7H) dione. AB - In the title compound, C(19)H(19)ClO(4), the central fused ring and the attached cyclo-hexene ring adopt envelope conformations, while the cyclo-hexane ring adopts a chair conformation. The crystal packing is stabilized by O-H?O hydrogen bonds, which link the mol-ecules into a chain along the b axis. Weak C-H?O bonds also occur. PMID- 22058986 TI - (E)-2-{[1-Carb-oxy-2-(1H-indol-3-yl)ethyl-iminio]meth-yl}-6-hy-droxy-phenolate. AB - In the zwitterionic title compound, C(18)H(16)N(2)O(4), the dihedral angle between the planes of the benzene and indole rings is 26.38 (10) degrees . An intra-molecular N-H?O hydrogen bond generates an S(6) ring motif. In the crystal, mol-ecules are linked through N-H?O, O-H?O and C-H?O hydrogen bonds into infinite chains propagating in [010]. PMID- 22058987 TI - 8-Phenyl-3,4,6,7,8,8a-hexahydro-1H-pyrrolo-[2,1-c][1,4]oxazin-6-one. AB - In the title compound, C(13)H(15)NO(2), the hexa-hydro-pyrrolo-[2,1 c][1,4]oxazine fragment is disordered over two conformations (A and B) in a 0.656 (5):0.344 (5) ratio. The five-membered ring is similarly disordered and adopts an envelope conformation in A, while in B this ring is nearly planar [maximum deviation = 0.088 (1) A]. The six-membered rings in both A and B exhibit chair conformations. In the crystal, weak inter-molecular C-H?O hydrogen bonds link the mol-ecules into ribbons propagating in [010]. PMID- 22058988 TI - 1,7,8,9,10,10-Hexachloro-4-(thio-phen-2-ylmeth-yl)-4-aza-tricyclo-[5.2.1.0]dec-8 ene-3,5-dione. AB - In the title compound, C(14)H(7)Cl(6)NO(2)S, the six-membered ring of the aza tricyclo system has a boat conformation whereas the five-membered rings have an envelope conformation. The thio-phene ring and the ring of the succinimide moiety enclose a dihedral angle of 67.2 (1) degrees . The crystal packing is stabilized by weak inter-molecular C-H?O hydrogen bonds. PMID- 22058989 TI - 3,3'-Dimethyl-1,1'-[2,2'-bipyridine-5,5'-diylbis(methyl-ene)]diimidazol-3-ium bis (hexa-fluoro-phosphate). AB - The title compound, C(20)H(22)N(6) (2+).2PF(6) (-), was prepared by the reaction of 5,5'-bis-(bromo-meth-yl)-2,2'-bipyridine with 1-methyl-imidazole. The main mol ecule lies on an inversion center located at the mid-point of the C-C bond joining the two pyridine rings. The asymmetric unit therefore contains one half mol-ecule and one hexa-fluoro-phosphate anion. The dihedral angle between the pyridine and imidazole rings is 76.93 (7) degrees . In the crystal, weak inter molecular C-H?F hydrogen bonds contribute to the stabilization of the packing. PMID- 22058990 TI - Phenyl 3-meth-oxy-4-phen-oxy-benzoate. AB - In the title mol-ecule, C(20)H(16)O(4), the two outermost phenyl rings form dihedral angles of 79.80 (7) and 69.35 (7) degrees with the central benzene ring. In the crystal structure, weak inter-molecular C-H?O inter-actions link the mol-ecules into ribbons propagating along [1[Formula: see text]0]. PMID- 22058991 TI - N-Methyl-l-leucyl-l-leucine hydro-chloride monohydrate. AB - In the title compound C(13)H(27)N(2)O(3) (+).Cl(-).H(2)O, obtained by deprotecting the amino and carboxyl groups of an inter-mediate in the synthesis of the cyclic penta-peptide Galaxamide, a number of hydrogen-bonding inter actions occur including aminium N-H?Cl, amide-carboxyl N-H?O, water O-H?Cl and carbox-yl-water O-H?O associations. The aminium N-H?Cl?H-N bridging extensions give rise to zigzag chains extending along the a axis, the overall two dimensional structure lying in the (110) plane. PMID- 22058992 TI - 9,9-Dimethyl-9,10-dihydroanthracene. AB - In the title compound, C(16)H(16), the central benzene ring adopts a boat conformation, with a dihedral angle of 34.7 (9) degrees between the mean planes of the two fused benzene rings. The two methyl groups at the apex of the central benzene ring are in axial and equatorial conformations. The crystal packing is stabilized by weak C-H?pi inter-molecular inter-actions. PMID- 22058993 TI - Ethyl 4-(phenyl-sulfon-yl)piperazine-1-carboxyl-ate. AB - In the title compound, C(13)H(18)N(2)O(4)S, the piperazine ring adopts a chair conformation. The dihedral angle between the least-squares planes through the piperazine and benzene rings is 73.23 (10) degrees . In the crystal, there are no classical hydrogen bonds but stabilization is provided by weak C-H?pi inter actions. PMID- 22058994 TI - 2-Amino-6-methyl-pyridinium 2-carb-oxy-benzoate. AB - In the title mol-ecular salt, C(6)H(9)N(2) (+).C(8)H(5)O(4) (-), an intra molecular O-H?O hydrogen bond occurs within the anion, thereby generating an S(7) ring, which may correlate with the fact that both the carb-oxy-lic acid and carboxyl-ate groups are almost coplanar with their attached rings [dihedral angles = 2.9 (3) and 5.2 (3) degrees , respectively]. In the crystal, each cation is linked to its adjacent anion by two N-H?O hydrogen bonds; the dihedral angle between the pyridine and benzene rings is 2.22 (10) degrees . The ion pairs are linked by further N-H?O inter-actions. PMID- 22058995 TI - (E)-1-(3,4-Dimeth-oxy-phen-yl)-3-[4-(methyl-sulfan-yl)phen-yl]prop-2-en-1-one. AB - In the title compound, C(18)H(18)O(3)S, the C=C double bond exists in an E configuration and the dihedral angle between the two benzene rings is 11.74 (8) degrees . In the crystal, mol-ecules are linked into a three-dimensional network by C-H?O hydrogen bonds. The crystal structure is also stabilized by weak C-H?pi inter-actions. PMID- 22058996 TI - Ethyl 1-[3-(1H-imidazol-1-yl)prop-yl]-2-(4-chloro-phen-yl)-1H-benzo[d]imidazole-5 carboxyl-ate dihydrate. AB - In the title compound, C(22)H(21)ClN(4)O(2).2H(2)O, the almost-planar benzimidazole ring system [maximum deviation 0.014 (1) A] is inclined at angles of 36.32 (5) and 74.75 (7) degrees with respect to the phenyl and imidazole rings, respectively. In the crystal structure, the water mol-ecules are linked to the organic mol-ecules to form a three-dimensional network via O-H?N and O-H?O hydrogen bonds. The packing is further consolidated by a pair of bifurcated C-H?O bonds, generating R(1) (2)(6) loops. C-H?pi inter-actions are also observed. PMID- 22058997 TI - (E)-1-(Pyridin-2-yl)-3-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one. AB - In the title heteroaryl chalcone derivative, C(17)H(17)NO(4), the dihedral angle between the pyridine and benzene rings is 10.82 (5) degrees . The two meth-oxy groups at the meta positions are essentially coplanar with the attached benzene rings [C-O-C-C torsion angles = -0.97 (14) and 179.47 (9) degrees ], whereas the meth-oxy group at the para position is twisted from the attached ring with a C-O C-C torsion angle of -104.48 (11) degrees . A C-H?O close contact involving two of the meth-oxy groups generates an S(6) ring motif. In the crystal, mol-ecules are linked by weak C-H?O inter-actions into columns along the b axis. PMID- 22058998 TI - Bis(4-fluoro-anilinium) sulfate. AB - In the crystal of the title molecular salt, 2C(6)H(7)FN(+).SO(4) (2-), the cations and anions are linked by N-H?O and C-H?O hydrogen bonds into sheets parallel to the ab plane. The crystal studied was found to be a racemic twin with a 0.50 (10):0.50 (10) domain ratio. PMID- 22058999 TI - 2-(5,6-Dihydro-benzimidazo[1,2-c]quinazolin-6-yl)-5-meth-oxy-phenol. AB - In the title quinazoline derivative, C(21)H(17)N(3)O(2), the benzimidazole unit makes dihedral angles of 8.29 (5) and 81.79 (5) degrees with the benzene rings of the quinazoline and meth-oxy-phenol units, respectively. The nitro-gen containing six-membered ring adopts a half-chair conformation. In the crystal, the mol-ecules are linked through O-H?N hydrogen bonds into screw chains along the b axis; adjacent chains are further connected by N-H?O hydrogen bonds, thereby forming a two-dimensional network lying parallel to the bc plane. Weak C H?pi and pi?pi inter-actions with centroid-centroid distances of 3.5258 (8) and 3.7184 (7) A are present and N?O [2.6816 (15) and 3.0519 (15) A] short contacts also occur. PMID- 22059000 TI - 2-[5-Methyl-2-(propan-2-yl)phen-oxy]-N'-{2-[5-methyl-2-(propan-2-yl)phen-oxy]acet yl}acetohydrazide. AB - The complete mol-ecule of the title compound, C(24)H(32)N(2)O(4), is generated by a crystallographic inversion center. The 1,2-diethyl-hydrazine moiety is nearly planar, with a maximum deviation of 0.024 (1) A, and is inclined at a dihedral angle of 54.20 (4) degrees with the phenyl ring. In the crystal, [001] chains are formed, with adjacent mol-ecules in the chain linked by pair of inter molecular N-H?O hydrogen bonds, generating R(2) (2)(10) ring motifs. Inter molecular C-H?O hydrogen bonds and C-H?pi inter-actions are also observed. PMID- 22059001 TI - Ethyl 5-methyl-1-(4-nitro-phen-yl)-1H-1,2,3-triazole-4-carboxyl-ate. AB - In the title compound, C(12)H(12)N(4)O(4), the 1,2,3-triazole ring and the nitro group form dihedral angles of 37.93 (5) and 8.97 (12) degrees , respectively, with the phenyl ring. The mol-ecular structure is stabilized by an intra molecular C-H?O hydrogen bond, which generates an S(6) ring motif. In the crystal, mol-ecules are linked by C-H?N hydrogen bonds into layers lying parallel to (100). The crystal structure is further consolidated by pi-pi [centroid centroid distance = 3.6059 (6) A] inter-actions. PMID- 22059002 TI - N-(4-Chloro-phen-yl)-N'-(3-methyl-phen-yl)succinamide monohydrate. AB - In the title hydrate, C(17)H(17)ClN(2)O(2).H(2)O, the dihedral angles formed by the aromatic rings of the chloro-benzene and methyl-benzene groups with the mean planes of their attached NH-C(O)-CH(2) fragments are 16.6 (2) and 22.8 (2) degrees , respectively. In the crystal, O-H?O and N-H?O hydrogen bonds link the components into a two-dimensional network parallel to the ab plane. PMID- 22059003 TI - N-(4-Chloro-phenyl)-N'-(4-methyl-phen-yl)succinamide. AB - The asymmetric unit of the title compound, C(17)H(17)ClN(2)O(2), contains one half-mol-ecule with a center of symmetry at the mid-point of the central C-C bond. The dihedral angle between the benzene ring and the adjacent NH-C(O)-CH(2) group is 39.9 (1) degrees . The methyl and Cl groups are disordered with respect to the para-positions of the benzene ring, with site-occupation factors of 0.5 each. In the crystal, inter-molecular N-H?O hydrogen bonds link the mol-ecules into chains parallel to the baxis. PMID- 22059004 TI - 4,4'-(Cyclo-hexane-1,1-di-yl)dianilinium dichloride monohydrate. AB - In the title compound, C(18)H(24)N(2) (2+).2Cl(-).H(2)O, both the cation and the water mol-ecule lie on a twofold crystallographic axis. In the cation, the two benzene rings are perpendicular to each other, making a symmetry-constrained dihedral angle of 90 degrees . In the crystal, N-H?Cl, O-H?Cl and N-H?O hydrogen bonds result in the formation of a three-dimensional network. PMID- 22059005 TI - 5-(4-Chloro-phen-yl)-1-methyl-3-phenyl-3,6,8,9-tetra-hydro-pyrazolo-[3,4-b]thio pyrano[4,3-d]pyridine. AB - The title compound, C(22)H(18)ClN(3)S, was synthesized by the reaction of 4 chloro-benzaldehyde, tetra-hydro-thio-pyran-4-one and 3-methyl-1-phenyl-1H pyrazol-5-amine in acetic acid without a catalyst. The pyridine and pyrazole rings are almost coplanar, the dihedral angle between their mean planes being 2.50 (1) degrees . The thio-pyran ring exhibits an envelope conformation. The crystal packing is stabilized by inter-molecular C-H?Cl hydrogen bonds and by C H?pi and pi-pi inter-actions [centroid-centroid distances of 3.825 (2) A between pyridine rings and 3.557 (2) A between pyrazole and pyridine rings. PMID- 22059006 TI - 4-(5-Phenyl-3-trifluoro-meth-yl-1H-pyrazol-1--yl)benzene-sulfonamide. AB - Significant twists between the aromatic rings are evident in the structure of the title compound, C(16)H(12)F(3)N(3)O(2)S. With reference to the pyrazole plane, the N- and C-bound benzene rings form dihedral angles of 57.12 (11) and 29.75 (11) degrees , respectively. The dihedral angle between the benzene rings is 52.82 (11) degrees . The presence of N-H?O(sulfonamide) and N-H?N(pyrazole) hydrogen bonds lead to supra-molecular tubes along the b-axis direction. These are connected into layers via C-H?O inter-actions involving a bifurcated O atom (not involved in the N-H?O hydrogen bonding). Layers stack along the a-axis direction. PMID- 22059007 TI - 4-(3-Methyl-5-phenyl-1H-pyrazol-1-yl)benzene-sulfonamide. AB - With respect to the planar five-membered ring of the title compound, C(16)H(15)N(3)O(2)S, the phenyl ring is aligned at 47.0 (1) degrees and the phenyl-ene ring at 37.6 (1) degrees . The amino group has the N atom in a pyramidal geometry; the group is a hydrogen-bond donor to the sulfonyl O atom of one mol-ecule and to the pyrazole N atom of another mol-ecule, resulting in the formation of a layer parallel to the bc plane. PMID- 22059008 TI - N,N'-Bis(2,3-dimeth-oxy-benzyl-idene)ethane-1,2-diamine. AB - The title compound, C(20)H(24)N(2)O(4), crystallizes with two half (centrosymmetric) mol-ecules in the asymmetric unit. There are only minor differences between the geometric parameters between these two mol-ecules. The two aromatic rings in both mol-ecules are mutually coplanar. PMID- 22059009 TI - (3-Benzoyl-phen-yl)(phen-yl)methanone. AB - Mol-ecules of the title compound, C(20)H(14)O(2), show approximate C(s) symmetry with the approximate mirror plane perpendicular to the central ring. The torsion angles about the acyclic bonds are 30.05 (15) and 30.77 (15) degrees in one half compared to -36.62 (14) and -18.60 (15) degrees in the other half of the mol ecule. The central aromatic ring makes dihedral angles of 47.78 (4) and 51.68 (3) degrees with the two terminal rings. PMID- 22059010 TI - (2RS,4'RS)-3'-(3-Chloro-4-meth-oxy-phen-yl)-4'-phenyl-4'H-spiro-[indene-2,5' isoxazol]-1(3H)-one ethanol monosolvate. AB - The title compound, C(23)H(17)ClN(2)O(3).C(2)H(6)O, is the stoichiometric 1:1 ethanol solvate of a racemic reaction product, which forms a conglomerate. The refined Flack parameter of 0.36 (3) indicates racemic twinning. In the structure, mol-ecules are linked into zigzag chains by a series of inter-molecular N-H?O and O-H?O hydrogen bonds. PMID- 22059011 TI - 3-Amino-1-(2H-1,3-benzodioxol-5-yl)-9,10-dihydro-phenanthrene-2,4-dicarbonitrile. AB - In the title compound, C(23)H(15)N(3)O(2), significant deviations from planarity are evidenced in the values of the dihedral angles formed between the amino benzene ring and the benzene rings of the 1,3-benzodioxole [65.38 (12) degrees ] and 1,2-dihydro-naphthalene [26.27 (14) degrees ] residues; the dioxole ring has an envelope conformation with the methyl-ene-C being the flap atom. The amino-H atoms form hydrogen bonds to one of the dioxole-O atoms and to one of the cyano-N atoms to generate a two-dimensional array with a zigzag topology that stacks along the ([Formula: see text] 0 2) plane. PMID- 22059012 TI - N,N'-Dibenzyl-N''-(2-chloro-acet-yl)-N,N'-dimethyl-phospho-ric triamide. AB - In the title mol-ecule, C(18)H(23)ClN(3)O(2)P, the P atom is bonded in a distorted tetra-hedral environment. The P=O and N-H groups are syn with respect to each other. The angles at the tertiary N atoms confirm their sp(2) character. In the crystal, pairs of inter-molecular P=O?H-N hydrogen bonds form centrosymmetric dimers. PMID- 22059013 TI - 5-Methyl-2-pyridone. AB - The crystal structure of the title compound, C(6)H(7)NO, is stabilized by inter molecular N-H?O hydrogen bonds, resulting in inversion dimers. The structure is further consolidated by weak C-H?O hydrogen bonds. PMID- 22059014 TI - (E)-2-Methyl-5-(thiophen-2-ylmethyl-idene)cyclopentan-1-one. AB - The exocyclic C=C double-bond in the title compound, C(11)H(12)OS, has an E configuration. The methyl-bearing C atom in the cyclo-pentane ring is disordered over two positions with a site-occupation factor of 0.899 (8) for the major occupied site. PMID- 22059015 TI - N-(2,6-Difluoro-benzo-yl)-P,P-bis-(pyrrolidin-1-yl)phosphinic amide. AB - The phosphoryl and carbonyl groups in the title compound, C(15)H(20)F(2)N(3)O(2)P, are anti with respect to each other (but the P- and C groups are separated by another atom) and the P atom is in a tetra-hedral coordination environment. Two C atoms in one of the pyrrolidinyl fragments are disordered over two sets of sites with occupancies of 0.746 (8) and 0.254 (8). The environments of the pyrrolidinyl N atoms show a slight deviation from planarity and none of the three N atoms is involved in any hydrogen bond as an acceptor. In the crystal, pairs of inter-molecular N-H?O hydrogen bonds form inversion dimers. PMID- 22059016 TI - 1-Benzoyl-3-(pyridin-2-yl)-1H-pyrazole. AB - In the title compound, C(15)H(11)N(3)O, the dihedral angle betwen the heterocyclic rings is 9.23 (5) degrees and the dihedral angle between the benzoyl and pyrazole rings is 58.64 (5) degrees . In the crystal, inversion dimers linked by pairs of C-H?O hydrogen bonds generate R(2) (2)(10) loops. The dimers stack into a column running parallel to the b-axis direction. PMID- 22059017 TI - 3-Amino-1-(4-meth-oxy-phen-yl)-9,10-dihydro-phenanthrene-2,4-dicarbonitrile. AB - In the title compound, C(23)H(17)N(3)O, significant deviations from planarity are evidenced. This is quanti-fied in the dihedral angles formed between the central amino-benzene ring and the benzene rings of the meth-oxy-benzene [67.93 (8) degrees ] and 1,2-dihydro-naphthalene [28.27 (8) degrees ] residues. In the crystal the amino-H atoms form hydrogen bonds to the meth-oxy-O atom and to one of the cyano-N atoms to generate a two-dimensional array with a zigzag topology that stacks along the ([Formula: see text][Formula: see text] 1) plane. PMID- 22059018 TI - Ethyl N-[4-(3-methyl-4,5-dihydro-benzo[g]indazol-1-yl)phenyl-sulfon-yl]thio carbam-ate ethanol monosolvate. AB - The title compound, C(21)H(20)N(3)O(3)S(2).CH(3)CH(2)OH, comprises two independent organic mol-ecules and two ethanol solvent mol-ecules. The mol-ecules are related by pseudo-mirror symmetry. In both mol-ecules, the N-bound benzene ring is twisted out of the plane of the pyrazole ring [the dihedral angles are 51.4 (3) and 44.1 (3) degrees , respectively]. Similarly, the benzene ring of the 1,2-dihydro-naphthalene residue is inclined with respect to the five-membered ring [dihedral angles 18.3 (3) and 22.2 (3) degrees ]. Overall, each mol-ecule has a flattened U shape. Dimeric aggregates mediated by O-H?N(pyrazole) and amide N-H?O hydrogen bonds feature in the crystal packing, whereby the ethanol mol ecules link the independent organic mol-ecules, leading to four-mol-ecule aggregates. PMID- 22059019 TI - 2,4-Bis(morpholin-4-yl)-6-phen-oxy-1,3,5-triazine. AB - In the title compound, C(17)H(21)N(5)O(3), the dihedral angle between the triazine and the phenyl ring is 80.31 (11) degrees . One of the morpholine rings is disordered over two orientations with site occupancies of 0.762 (10) and 0.238 (10). Both morpholine rings in the mol-ecule adopt chair conformations. PMID- 22059020 TI - N-Benzyl-1,3-dide-oxy-1,3-imino-l-xylitol. AB - The structure determination confirms the stereochemistry of the title compound, C(12)H(17)NO(3), which contains a four-membered azetidine ring system. The absolute configuration was determined by the use of d-glucose as the starting material. In the crystal, O-H?O and O-H?N hydrogen bonds link the mol-ecules into layers in the ab plane. PMID- 22059021 TI - N-(4-Chloro-phen-yl)-4-methyl-piperazine-1-carboxamide. AB - In the title compound, C(12)H(16)ClN(3)O, the piperazine ring has a chair conformation. Within this ring, the N-methyl nitro-gen atom has a pyramidal geometry and the N-carboxamide nitro-gen atom is almost planar (bond-angle sum = 359.8 degrees ). In the crystal, the mol-ecules are linked by N-H?O hydrogen bonds into C(4) chains propagating in [010]. PMID- 22059022 TI - 4-(Diphenyl-phosphan-yl)benzoic acid. AB - In the title compound, C(19)H(15)O(2)P, the dihedral angles between the benzoic acid ring and the phenyl rings are 75.64 (7) and 80.88 (7) degrees ; the dihedral angle between the phenyl rings is 81.35 (7) degrees . In the crystal, inversion dimers linked by pairs of O-H?O hydrogen bonds generate R(2) (2)(8) loops between the head-to-head carb-oxy-lic acid groups. PMID- 22059023 TI - N-[4-(Ethyl-sulfamo-yl)phen-yl]acetamide. AB - The title compound, C(10)H(14)N(2)O(3)S, crystallized with two mol-ecules (A and B) in the asymmetric unit. The terminal methyl group of the ethyl-sulfonamide moiety in mol-ecule B is disordered over two sets of sites with an occupancy ratio of 0.61 (1):0.39 (1). Both mol-ecules have L-shaped conformations. In mol ecule A, the dihedral angles between the benzene ring and its ethyl-sulfonamide and methyl-amide substituents are 83.5 (3) and 13.34 (18) degrees , respectively. Equivalent values for mol-ecule B are 87.9 (3) and 6.32 (16) degrees , respectively. The C-S-N-C torsion angles are 66.5 (3) degrees for A and -64.4 (3) degrees for B, indicating similar twists about the S-N bonds, but in opposite senses. In the crystal, the A mol-ecules are linked by pairs of N(s)-H?O (s = sulfonamide) hydrogen bonds, generating inversion dimers containing R(2) (2)(8) rings, while the B mol-ecules are linked by N(s)-H?O hydrogen bonds into C(10) [100] chains. Finally, N(a)-H?O (a = amide) hydrogen bonds link the A-mol ecule dimers and B-mol-ecule chains into a three-dimensional network. PMID- 22059024 TI - N-(2,3-Dimethyl-phen-yl)-4-methylbenzamide. AB - In the mol-ecule of the title compound, C(16)H(17)NO, the two aromatic rings are almost perpendicular to each other [dihedral angle 85.90 (5) degrees ]. The crystal structure is stabilized by inter-molecular N-H?O hydrogen bonds which link the mol-ecules, forming C(4) chains running along the c axis. PMID- 22059025 TI - N-Cyclo-propyl-N-[2-(2,4-difluoro-phen-yl)-2-hy-droxy-1-(1H-1,2,4-triazol-1 yl)prop-yl]-2-(5-methyl-2,4-dioxo-1,2,3,4-tetra-hydro-pyrimidin-1-yl)acetamide dichloro-methane 0.62-solvate. AB - In the title compound, C(21)H(22)F(2)N(6)O(4).0.62CH(2)Cl(2), the difluoro substituted benzene ring forms dihedral angles of 54.6 (3) degrees with the mean plane of the thymine ring and 50.9 (2) degrees with the triazole ring. The dihedral angle between the thymine and triazole rings is 7.4 (3) degrees . In the crystal, inter-molecular N-H?N and O-H?O hydrogen bonds link the main mol-ecules into chains along [10[Formula: see text]]. The CH(2)Cl(2) solvent mol-ecule was refined as partial occupancy over two sets of sites with refined occupancies of 0.308 (9) and 0.310 (8). PMID- 22059026 TI - N,N'-Bis[1-(thiophen-2-yl)ethylidene]ethane-1,2-diamine. AB - Mol-ecules of the title compound, C(14)H(16)N(2)S(2), have a centre of inversion in the middle of the -CH(2)-CH(2)- bond; the (C(4)H(3)S)(CH(3))C=N-CH(2)- moiety is almost planar (r.m.s. deviation for non-H atoms 0.027 A). PMID- 22059027 TI - 4-(3,7-Dimethyl-4-oxo-4,5-dihydro-isoxazolo[4,5-d]pyridazin-5-yl)benzene sulfonamide. AB - The nine-membered fused-ring system of the title pyridazine derivative, C(13)H(12)N(4)O(4)S, is approximately planar (r.m.s. deviation 0.027 A), and the benzene ring of the phenyl-sulfamide substituent is aligned at 43.5 (1) degrees to the fused-ring system. The amine group of the sulfonamide substituent forms an N-H?O hydrogen bond to the ketonic O atom of two neigboring mol-ecules to generate a chain running along the c axis. PMID- 22059028 TI - 2,7-Dimethyl-1,3-thia-zolo[4,5-d]pyridazin-4(5H)-one. AB - The nine-membered fused-ring system of the title pyridazine derivative, C(7)H(7)N(3)OS, is almost planar (r.m.s. deviation 0.012 A). In the crystal, the amino H atom forms a hydrogen bond to the ketonic O atom of a neighboring mol ecule to generate a centrosymmetric dimer. PMID- 22059029 TI - 4-(4-Meth-oxy-phen-yl)-2-oxo-1,2,5,6-tetra-hydro-benzo[h]quinoline-3-carbo nitrile. AB - In the mol-ecule of the title compound, C(21)H(16)N(2)O(2), the tetra-hydro benzo[h]quinoline fused-ring system is buckled owing to the ethyl-ene -CH(2)CH(2) fragment, the benzene ring and the pyridine ring being twisted by 19.7 (1) degrees . The 4-substituted aromatic ring is bent away from the pyridine ring by 50.3 (1) degrees in order to avoid crowding the cyanide substituent. In the crystal, two mol-ecules are linked by a pair of N-H?O hydrogen bonds to form a centrosymmetric dimer. PMID- 22059030 TI - 4-(5,3'-Dimethyl-5'-oxo-2-phenyl-2',5'-dihydro-2H-[3,4']bipyrazol-1'-yl)benzene sulfonamide monohydrate. AB - In the title compound, C(20)H(19)N(5)O(3)S.H(2)O, the pyrazole ring is connected to a pyrazolone ring, and the two five-membered rings are aligned at 45.0 (1) degrees . The pyrazole ring is connected to a phenyl ring and the two are twisted by 42.7 (1) degrees . Finally, the pyrazolone ring is connected to a benzene ring and the two are twisted by 19.5 (1) degrees . The N-H and -NH(2) portions and the solvent water mol-ecules are engaged in N-H?N, N-H?O and O-H?O hydrogen-bonding inter-actions to generate a three-dimensional network. PMID- 22059031 TI - 2-(Tritylsulfan-yl)ethyl 2-iodo-benzoate. AB - The methine C atom of the triphenyl-methyl group in the title compound, C(28)H(23)IO(2)S, is slightly flattened out [SigmaC(phen-yl)-C-C(phen-yl) = 335.6 (5) degrees ]. The -C-O-C-C-S- chain connecting the triphenyl-methyl group and the aromatic ring adopts an extended zigzag conformation, these five atoms lying on an approximate plane (r.m.s. deviation = 0.120 A). PMID- 22059032 TI - A triclinic modification of 3,4-dihy-droxy-benzoic acid monohydrate. AB - The unit cell of the title compound, C(7)H(6)O(4).H(2)O, features four independent formula units; the individual carb-oxy-lic acid mol-ecules themselves are nearly planar (r.m.s. deviations = 0.0189, 0.0334, 0.0356 and 0.0441 A). Two independent mol-ecules each form two hydrogen bonds by acid-carbonyl O-H?O inter actions and the dimers are also nearly planar (r.m.s. deviations = 0.039 and 0.049 A). The two independent dimers are aligned at 44.5 (1) degrees . Other O H?O inter-actions involving the hy-droxy groups and water mol-ecules give rise to a three-dimensional network. PMID- 22059033 TI - (2R)-N-(2-Benzoyl-phen-yl)-1-benzyl-pyrrolidine-2-carboxamide. AB - In the title compound, C(25)H(24)N(2)O(2), the dihedral angle between the two benzene rings of the benzophenone moiety is 59.10 (6) degrees . An intra molecular, bifurcated N-H?(O,N) hydrogen bond, which generates S(6) and S(5) rings, respectively, helps to establish the overall conformation of the mol ecule. PMID- 22059034 TI - 2-(4-Fluoro-phen-yl)-1-(phenyl-sulfin-yl)-naphtho-[2,1-b]furan. AB - In the title compound, C(24)H(15)FO(2)S, the 4-fluoro-phenyl ring makes a dihedral angle of 19.43 (4) degrees with the mean plane of the naphtho-furan fragment. The dihedral angle between the phenyl ring and the mean plane of the naphtho-furan fragment is 85.83 (4) degrees . In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds. PMID- 22059035 TI - (7R,8S,9S,12S)-1-(4-Chloro-benz-yloxy)-13,14-didehydro-12-hy-droxy-2,13-dimeth oxy-N-methyl-morphinane. AB - The title compound, C(26)H(30)ClNO(4), a sinomenine derivative, has five six membered rings, two of which are aromatic, with a dihedral angle of 34.13 (20) degrees between these. The N-containing ring and the fourth ring exhibit chair conformations, while the fifth ring approximates an envelope conformation. A single inter-molecular O-H?N hydrogen-bonding inter-action gives a one dimensional chain structure which extends along the a axis. The absolute configuration for the mol-ecule has been determined. PMID- 22059036 TI - Ethane-1,2-diaminium bis-{5-[4-(1H-tetra-zol-5-yl)phen-yl]tetra-zolide} dihydrate. AB - In the two anions of the title salt, C(2)H(10)N(2) (2+).2C(8)H(5)N(8) (-).2H(2)O, the central aromatic rings make dihedral angles of 13.53 (6) and 6.53 (7) degrees with the deprotonated tetra-zole rings, and 11.39 (6) and 10.41 (9) degrees with the other tetra-zole groups. In the crystal, the cations, anions and water mol-ecules are linked by an extensive O-H?N, N-H?O and N-H?N hydrogen-bond network into two-dimensional wave-like duplex sheets extending parallel to the bc plane. pi-pi stacking inter-actions between benzene rings [inter-centroid distances are 3.8482 (4) and 3.9621 (5) A] and between tetra-zole rings [inter centroid distances are 3.4350 (4) and 3.7169 (4) A] further consolidate the crystal structure. PMID- 22059037 TI - 3-[3-Methyl-4-(3-nitro-benzyl-idene-amino)-5-sulfanyl-idene-4,5-dihydro-1H-1,2,4 triazol-1-yl]-1,3-diphenyl-propan-1-one. AB - In the title mol-ecule, C(25)H(21)N(5)O(3)S, the triazole ring forms dihedral angles of 21.4 (2), 61.4 (2) and 102.4 (2) degrees with the nitro-phenyl and two phenyl rings, respectively. In the crystal, weak C-H?O hydrogen bonds and pi-pi inter-actions between the benzene rings from neighbouring mol-ecules [with a centroid-centroid distance of 3.571 (3) A] consolidate the crystal packing. PMID- 22059038 TI - 1-(Biphenyl-4-ylcarbon-yl)-3-(4-nitro-phen-yl)thio-urea. AB - In the title compound, C(20)H(15)N(3)O(3)S, the two benzene rings of the biphenyl group form a dihedral angle of 40.11 (15) degrees . The conformation of the mol ecule is trans-cis and is stabilized by two intra-molecular N-H?O and C-H?S hydrogen bonds. In the crystal structure, the mol-ecules are linked by weak pi-pi stacking inter-actions [centroid-centroid distance = 3.991 (2) A]. PMID- 22059039 TI - 11-Hy-droxy-9-(prop-2-en-1-yl)-9,10-dihydro-9,10-propano-anthracen-12-one. AB - In the title compound, C(20)H(18)O(2), the central six-membered ring adopts a boat conformation and the terminal benzene rings make a dihedral angle of 42.66 (4) degrees with each other. In the crystal structure, the O-H group forms both an intra- and an inter-molecular O-H?O hydrogen bond; the former generates an S(5) ring and the latter leads to inversion-generated R(2) (2)(10) loops. The dimers are further linked into ribbons propagating along the a axis by C-H?O inter-actions, and the packing is consolidated by weak C-H?pi inter-actions. PMID- 22059040 TI - (E)-2-[4-(Diethyl-amino)-styr-yl]-1-methyl-pyridinium 4-chloro-benzene-sulfonate monohydrate. AB - In the title hydrated mol-ecular salt, C(18)H(23)N(2) (+).C(6)H(4)ClO(3)S( ).H(2)O, which shows moderate biological activity against methicillin-resistant Staphylococcus aureus (MRSA), one ethyl group of the 2-[4-(diethyl-amino)-styr yl]-1-methyl-pyridinium cation is disordered over two orientations in a 0.604 (13):0.396 (13) ratio. The main part of the cation is nearly planar with a dihedral angle of 4.50 (10) degrees between the pyridinium and benzene rings. In the crystal, the components are linked by O-H?O hydrogen bonds and C-H?O weak inter-actions. Aromatic pi-pi stacking inter-actions with centroid-centroid separations of 3.7363 (12) and 3.7490 (13) A also occur. PMID- 22059041 TI - 2-Methyl-5-nitro-1H-benzimidazol-6-amine dihydrate. AB - The title benzimidazole mol-ecule, C(8)H(8)N(4)O(2).2H(2)O, is planar with a maximum deviation of 0.079 (2) A (for one of the O atoms in the nitro group). It crystallized as a dihydrate and inter-molecular O-H?O and N-H?O hydrogen bonds link the uncoordinated water mol-ecules, and the nitro and amine groups, respectively. In the crystal, N-H?O, O-H?N, O-H?O and C-H?O hydrogen bonds link the mol-ecules to form a three-dimensional network. A pi-pi contact between the benzene rings, [centroid-centroid distance = 3.588 (1) A] may further stabilize the crystal structure. PMID- 22059042 TI - N-(4-Chloro-phen-yl)morpholine-4-carboxamide. AB - In the title mol-ecule, C(11)H(13)ClN(2)O(2), the morpholine ring has a chair conformation. In the crystal, mol-ecules are linked into chains along [100] by N H?O hydrogen bonds. PMID- 22059043 TI - (E)-3-(2-Hy-droxy-5-methyl-phenyl-imino)-indolin-2-one. AB - In the title compound, C(15)H(12)N(2)O(2), the dihedral angle between the two benzene rings is 83.55 (11) degrees In the crystal, the molecules are linked by O-H?O and N-H?O hydrogen bonds. PMID- 22059044 TI - 3-(9H-Carbazol-9-yl)-2H-chromen-2-one. AB - The title compound, C(21)H(13)NO(2), was prepared as an example of a new synthesis of carbazoles from a cyclic dibenzo-iodo-lium salt via a twofold Pd catalysed aryl-ation of a primary amine. The two essentially planar pi-subsystems [maximum deviations from the mean square plane of 0.038 (2) A in the carbazole and 0.059 (2) A in the coumarine unit] open a dihedral angle of 63.05 (4) degrees . Two mol-ecules form a centrosymmetrical pair connected via pi-pi inter-actions between the pyrrole and pyrone rings [centroid-centroid distance = 3.882 (1) A] and one benzene of the carbazole and the pyrone unit [centroid-centroid distance 3.824 (1) A]. The lattice is stabilized by C-H?O bridging to both coumarin O atoms. PMID- 22059045 TI - 4,4'-Bipyridine-4-(p-toluene-sulfonamido)-benzoic acid (1/2). AB - In the title compound, C(14)H(13)NO(4)S.0.5C(10)H(8)N(2), the two benzene rings are nearly perpendicular to each other [dihedral angle = 83.21 (10) degrees ]. The bipyridine mol-ecule is centrosymmetric, the mid-point of the C-C bond linking the pyridine rings being located on an inversion center. Inter-molecular N-H?O and O-H?N hydrogen bonds and weak inter-molecular C-H?O hydrogen bonds are present in the crystal structure. PMID- 22059046 TI - 4alpha,6alpha-Dihy-droxy-1beta-methyl-sulfonyl-8alpha,9alpha-ep-oxy-2beta,12 epoxymethano-beta-dihydro-agarofuran. AB - The title mol-ecule, C(16)H(24)O(8)S, is a dihydro-agrofuran derivative and has a heteropolycyclic structure. One cyclohexane ring exhibits a chair conformation and the other a non-chair conformation. In the crystal structure there is an inter-molecular C-H?O hydrogen-bonding inter-action to stabilize the packing. PMID- 22059047 TI - Benzyl (E)-3-(2-methyl-benzyl-idene)dithio-carbazate. AB - The title compound, C(16)H(16)N(2)S(2), was obtained from the condensation reaction of benzyl dithio-carbazate and 2-methyl-benzaldehyde. The asymmetric unit contains two independent mol-ecules. In both mol-ecules, the methyl-phenyl ring and the dithio-carbazate fragment are located on opposite sides of the C=N bond, showing an E conformation. In each mol-ecule, the dithio-carbazate fragment is approximately planar, the r.m.s deviations being 0.018 and 0.025 A. The mean plane of dithio-carbazate group is oriented at dihedral angles of 7.9 (3) and 68.24 (12) degrees , respectively, to the methyl-phenyl and phenyl rings in one mol-ecule, while the corresponding angles in the other mol-ecule are 10.9 (3) and 69.76 (16) degrees . Inter-molecular N-H?S hydrogen bonding occurs in the crystal structure to generate inversion dimers for both molecules. PMID- 22059048 TI - (E)-N'-[1-(Thio-phen-2-yl)ethyl-idene]benzohydrazide. AB - The title compound, C(13)H(12)N(2)OS, was obtained from the condensation reaction of 2-acetyl-thio-phene and benzohydrazide. In the mol-ecule, the formohydrazide fragment is approximately planar (r.m.s deviation = 0.0146 A) and the mean plane is oriented at dihedral angles of 24.47 (11) and 28.86 (13) degrees , respectively, to the phenyl and thio-phene rings. The thio-phene and phenyl rings make a dihedral angle of 53.21 (8) degrees . The benzamide fragment and thio phene ring are located on the opposite sides of the C=N bond, showing an E conformation. Classical inter-molecular N-H?O hydrogen bonds and weak C-H?O inter actions are present in the crystal structure: three such bonds occur to the same O-atom acceptor. PMID- 22059049 TI - Methyl 3,5-dibromo-2-diacetyl-amino-benzoate. AB - The title methyl benzoate compound, C(12)H(11)Br(2)NO(4), consists of an ortho substituted diacetyl-amino group and meta-substituted Br atoms. The crystal packing is stabilized by weak inter-molecular C-H?O inter-actions. PMID- 22059050 TI - Bis(ethano-laminium) succinate-succinic acid (1/1). AB - The asymmetric unit of the title compound, 2C(2)H(8)NO(+).C(4)H(4)O(4) (2 ).C(4)H(6)O(4), consists of half a succinate anion, half a succinic acid mol ecule and one ethano-laminium cation. The succinate anion and succinic acid mol ecule, both of which are located on inversion centres, are linked by O-H?O hydrogen bonds, forming a chain along the [2[Formula: see text]0] direction. The chain and the ethano-laminium cation are further connected by O-H?O and N-H?O hydrogen bonds. PMID- 22059051 TI - 2-[(Naphthalen-1-yl-methyl-idene)amino]-5-methyl-phenol. AB - The title compound, C(18)H(15)NO, is a Schiff base prepared from an acid catalyzed condensation reaction between 1-naphthaldehyde and 6-amino-m-cresol. Intra-molecular hydrogen bonding occurs via an O-H?N inter-action, generating an S(5) ring motif. Neighboring phenol groups participate in inter-molecular hydrogen bonding through an O-H?O inter-action, forming chains. The O atom of the phenol group also participates in an intermolecular C-H?O interaction with an H atom of one of the naphthalene rings. The C-N=C-C torsion angle between the phenol and naphthalene rings is -179.8 (2) degrees . Crystal packing involves stacks with the mol-ecules inter-acting through the pi-systems of the C=N with both the phenol system and one of the naphthalene rings. PMID- 22059052 TI - 1-(4-Bromo-phen-yl)-2-methyl-1H-indole-3-carbonitrile. AB - In the title compound, C(16)H(11)BrN(2), the dihedral angle between the indole ring system and the phenyl ring is 58.85 (11) degrees . PMID- 22059053 TI - 2-Amino-pyridin-3-ol. AB - The molecule of the title pyridine derivative, C(5)H(6)N(2)O, shows approximate C(s) symmetry. Intra-cyclic angles cover the range 118.34 (10)-123.11 (10) degrees . In the crystal, O-H?N, N-H?O and N-H?N hydrogen bonds connect the mol ecules into double layers perpendicular to the a axis. The shortest centroid centroid distance between two pi-systems is 3.8887 (7) A. PMID- 22059054 TI - The 4-(3-chloro-4-methyl-phen-yl)-1,2,3,5-dithia-diazol-3-yl radical. AB - The asymmetric unit of the title compound, C(8)H(6)ClN(2)S(2), comprises two mol ecules forming a dimer via pi-pi stacking inter-actions [centroid-centroid distance = 3.634 (10) A] and intra-dimer S?S contacts [3.012 (4) and 3.158 (4) A] between the two mol-ecules in a cis-antarafacial arrangement. PMID- 22059055 TI - 2-(1-Adamant-yl)-1-(3-amino-phen-yl)ethanol. AB - In the crystal structure of the title compound, C(18)H(25)NO, mol-ecules are linked via O-H?N hydrogen bonds, forming chains parallel to the c axis. Additional weak N-H?O inter-actions stabilize the crystal packing. The adamantane cage consists of three fused cyclo-hexane rings in almost ideal chair conformations, with C-C-C angles in the range 107.9 (10)-111.3 (11) degrees . PMID- 22059056 TI - 7-Benzyl-2,7-diaza-spiro-[4.4]nonan-1-one. AB - In the title compound, C(14)H(18)N(2)O, both the spiro-linked five-membered rings adopt envelope conformations, with a C atom as the flap in one ring and an N atom in the other. The dihedral angle between the two four-atom planes is 80.46 (8) degrees . In the crystal, the mol-ecules are linked by N-H?O hydrogen bonds to generate C(4) chains propagating in [010]. PMID- 22059057 TI - 2-(5,6-Dihydro-benzimidazo[1,2-c]quinazolin-6-yl)-6-eth-oxy-phenol. AB - In the title compound, C(22)H(19)N(3)O(2), the phenol ring forms dihedral angles of 88.93 (10) and 87.95 (12) degrees with the benzimidazole system and the quinazoline benzene ring, respectively. In the crystal, mol-ecules are linked via O-H?N hydrogen bonds into infinite chains along [100]. An intra-molecular N-H?O hydrogen bond generates an S(6) ring. PMID- 22059058 TI - 3,5-Dimethyl-4-nitroso-1H-pyrazole. AB - In the unit cell of the title compound, C(5)H(7)N(3)O, there are two conformers (A and B) which differ in the position of the oxime group with respect to the protonated pyrazole nitro-gen (trans in the A conformer and cis in the B conformer) and in the geometric parameters. The oxime group exists in the nitroso form in both conformers. In the crystal, mol-ecules are linked by inter-molecular N-H?O and N-H?N hydrogen bonds into zigzag-like chains along the b axis. PMID- 22059059 TI - 8-(Naphthalen-1-yl)quinoline. AB - In the title mol-ecule, C(19)H(13)N, the angle between the mean planes of the naphthalene and quinoline ring systems is 68.59 (2) degrees . The compound is of inter-est with respect to its potential for spontaneous resolution. In the crystal structure, the R and S isomers are arranged in alternating homochiral layers. The mol-ecules of a given layer are oriented with their major axes (i.e. the axis perpendicular to the interannular bond) in the same direction and their naphthalene and quinoline ring systems are arranged parallel. Like the configurations, this orientation alternates in adjacent layers. PMID- 22059060 TI - rac-Phenyl (benzylamido)(p-tolyl-amido)-phosphinate. AB - The title compound, C(20)H(21)N(2)O(2)P, was synthesized from (RS) (C(6)H(5)O)P(O)Cl(NHC(6)H(4)-p-CH(3)) and benzyl-amine. The product crystallizes as a racemate in a polar space group. The phospho-rus atom has a distorted tetra hedral configuration: the bond angles at the P atom are in the range 103.2 (1) 118.4 (1) degrees . The P-N(benzyl-amido) bond [1.615 (2) A] is slightly shorter than the P-N(p-tolyl-amido) bond [1.630 (2) A]. Both N-H groups adopt an anti orientation relative to the phosphoryl group. In the crystal, the adjacent mol ecules are linked via N-H?O hydrogen bonds, forming R(2) (2)(8) rings, into a one dimensional arrangement parallel to the x axis. PMID- 22059061 TI - Chloro-bis-(naphthalen-1-yl)phosphane. AB - In the title compound, C(20)H(14)ClP, the dihedral angle between the naphthyl rings is 81.77 (6) degrees . The crystal packing suggests weak pi-pi stacking inter-actions between the naphthyl rings in adjacent units [minimum ring centroid separation 3.7625 (13) A]. PMID- 22059062 TI - Methyl 4-hy-droxy-2-meth-oxy-carbonyl-methyl-1,1-dioxo-1,2-dihydro-1lambda,2 benzothia-zine-3-carboxyl-ate. AB - There are two independent mol-ecules in the asymmetric unit of the title compound, C(13)H(13)NO(7)S, which have almost identical geometries. The thia-zine ring adopts a sofa conformation in both mol-ecules and the mol-ecular conformations are stabilized by intramolecular O-H?O hydrogen bonds. Inter molecular C-H?O hydrogen bonds stabilize the crystal packing. PMID- 22059063 TI - 3,5-Dimethyl-1H-pyrazole-2-hy-droxy-5-(phenyl-diazen-yl)benzoic acid (1/1). AB - There are two independent 3,5-dimethyl-pyrazole and two independent 2-hy-droxy-5 (phenyl-diazen-yl)benzoic acid mol-ecules [in which intra-molecular O-H?O bonds form S(6) graph-set motifs] in the asymmetric unit of the title compound, C(5)H(8)N(2).C(13)H(10)N(2)O(3). In the crystal, the components are linked by inter-molecular O-H?O, O-H?N and N-H?O hydrogen bonds, forming four-component clusters. Further stabilization is provided by weak C-H?pi inter-actions. PMID- 22059064 TI - 6-De-oxy-3,4-O-isopropyl-idene-2-C-methyl-l-galactono-1,5-lactone. AB - X-ray crystallography unequivocally confirmed the stereochemistry of the 2-C methyl group in the title mol-ecule, C(10)H(16)O(5), in which the 1,5-lactone ring exists in a boat conformation. The absolute stereochemistry was determined by the use of d-ribose in the synthesis. The crystal exists as O-H?O hydrogen bonded chains of mol-ecules running parallel to the a axis with each mol-ecule acting as a donor and acceptor for one hydrogen bond. PMID- 22059065 TI - 3-{4-[(2-Hy-droxy-benzyl-idene)amino]-3-methyl-5-sulfanyl-idene-4,5-dihydro-1H 1,2,4-triazol-1-yl}-1,3-diphenyl-propan-1-one. AB - There are two crystallographically independent mol-ecules (A and B) in the asymmetric unit of the title compound, C(25)H(22)N(4)O(2)S, with almost identical mol-ecular conformations. The hy-droxy-phenyl ring plane and the 1,2,4-triazole ring form dihedral angles of 17.1 (2) and 7.4 (2) degrees in A and B, respectively. The dihedral angles between 1,2,4-triazole ring and the other two phenyl rings are 89.6 (3) and 83.3 (2) degrees in mol-ecule A, and 89.2 (3) and 82.2 (2) degrees in mol-ecule B. One intra-molecular O-H?N hydrogen bond is present in each mol-ecule. Weak inter-molecular C-H?O hydrogen bonds consolidate the crystal packing. PMID- 22059066 TI - 3-{4-[(4-Meth-oxy-benzyl-idene)amino]-3-phenyl-5-sulfanyl-idene-4,5-dihydro-1H 1,2,4-triazol-1-yl}-1,3-diphenyl-propan-1-one. AB - In the title mol-ecule, C(31)H(26)N(4)O(2)S, the phenyl ring attached to the 1,2,4-triazole ring forms dihedral angles of 65.4 (2), 63.4 (2) and 62.2 (2) degrees with the other three rings. The 1,2,4-triazole ring makes dihedral angles of 78.0 (2), 87.9 (2), 24.9 (2) and 62.8 (2) degrees with three phenyl rings and the methoxyphenyl ring. PMID- 22059067 TI - 3-[2-(2,6-Dichloro-anilino)benz-yl]-4-[(4-meth-oxy-benzyl-idene)amino]-1H-1,2,4 triazole-5(4H)-thione. AB - In the title compound, C(23)H(19)Cl(2)N(5)OS, the triazole ring makes dihedral angles of 24.81 (18), 69.94 (19) and 35.68 (18) degrees with the dichloro phenyl, benzene and meth-oxy-phenyl rings, respectively. An intra-molecular N-H?N hydrogen bond occurs. In the crystal, inversion dimers linked by pairs of N-H?S hydrogen bonds occur. In addition, there are weak C-H?pi inter-actions involving the dichloro-phenyl and triazole rings. PMID- 22059068 TI - Bis(2-bromo-5-methyl-phen-oxy)methane. AB - The complete mol-ecule of the title compund, C(15)H(14)Br(2)O(2), is generated by the application of crystallographic twofold symmetry, with the central C atom lying on the rotation axis. The dihedral angle between the benzene rings is 62.4 (3) degrees . In the crystal, short Br?Br contacts [3.4885 (16) A] occur. PMID- 22059069 TI - 7-Amino-1,8-naphthyridin-2(1H)-one monohydrate. AB - In the crystal structure of the title compound, C(8)H(7)N(3)O.H(2)O, adjacent organic mol-ecules are linked together into a tape along the a axis through N-H?N and N-H?O hydrogen bonds. On the other hand, water mol-ecules are linked together to form a chain along the b axis through O-H?O hydrogen bonds. The water chains and the organic mol-ecular tapes are further connected by inter-molecular O-H?O hydrogen bonds, forming a three-dimensional network. In addition, a pi-pi stacking inter-action between the 1,8-naphthyridine ring systems with an inter planar separation of 3.246 (1) A and a centroid-centroid distance of 3.825 (2) A is observed. PMID- 22059070 TI - 1-Methyl-4-(4-nitro-benzo-yl)pyridinium perchlorate. AB - In the main mol-ecule of the title compound, C(13)H(11)N(2)O(3) (+).ClO(4) (-), the two aromatic rings are twisted by 56.19 (3) degrees relative to each other and the nitro group is not coplanar with the benzene ring [36.43 (4) degrees ]. The crystal packing is dominated by infinite aromatic stacks in the a-axis direction. These are formed by the benzene units of the mol-ecule featuring an alternating arrangement, which explains the two different distances of 3.3860 (4) and 3.4907 (4) A for the aromatic units (these are the perpendicular distances of the centroid of one aromatic ring on the mean plane of the other other aromatic ring). Adjacent stacks are connected by pi-pi stacking between two pyridinium units [3.5949 (4) A] and weak C-H?O inter-actions. The perchlorate anions are accomodated in the lattice voids connected to the cation via weak C-H?O contacts between the O atoms of the anion and various aromatic as well as methyl H atoms. PMID- 22059071 TI - The n250 brain potential to personally familiar and newly learned faces and objects. AB - Studies employing event-related potentials have shown that when participants are monitoring for a novel target face, the presentation of their own face elicits an enhanced negative brain potential in posterior channels approximately 250 ms after stimulus onset. Here, we investigate whether the own face N250 effect generalizes to other highly familiar objects, specifically, images of the participant's own dog and own car. In our experiments, participants were asked to monitor for a pre-experimentally unfamiliar target face (Joe), a target dog (Experiment 1: Joe's Dog) or a target car (Experiment 2: Joe's Car). The target face and object stimuli were presented with non-target foils that included novel face and object stimuli, the participant's own face, their own dog (Experiment 1), and their own car (Experiment 2). The consistent findings across the two experiments were the following: (1) the N250 potential differentiated the target faces and objects from the non-target face and object foils and (2) despite being non-targets, the own face and own objects produced an N250 response that was equal in magnitude to the target faces and objects by the end of the experiment. Thus, as indicated by its response to personally familiar and recently familiarized faces and objects, the N250 component is a sensitive index of individuated representations in visual memory. PMID- 22059072 TI - Awareness of Central Luminance Edge is Crucial for the Craik-O'Brien-Cornsweet Effect. AB - The Craik-O'Brien-Cornsweet (COC) effect demonstrates that perceived lightness depends not only on the retinal input at corresponding visual areas but also on distal retinal inputs. In the COC effect, the central edge of an opposing pair of luminance gradients (COC edge) makes adjoining regions with identical luminance appear to be different. To investigate the underlying mechanisms of the effect, we examined whether the subjective awareness of the COC edge is necessary for the generation of the effect. We manipulated the visibility of the COC edge using visual backward masking and continuous flash suppression while monitoring subjective reports regarding online percepts and aftereffects of adaptation. Psychophysical results showed that the online percept of the COC effect nearly vanishes in conditions where the COC edge is rendered invisible. On the other hand, the results of adaptation experiments showed that the COC edge is still processed at the early stage even under the perceptual suppression. These results suggest that processing of the COC edge at the early stage is not sufficient for generating the COC effect, and that subjective awareness of the COC edge is necessary. PMID- 22059073 TI - A case of angioleiomyoma with epithelioid granuloma. AB - We describe a 61-year-old Japanese woman who had been aware of a lesion on her left thigh for 10 years. Pathological examination demonstrated a well circumscribed encapsulated nodule at the dermal-subcutaneous boundary, composed of eosinophilic spindle cell bundles, connective tissue, and numerous small vessels. Immunohistochemically, these eosinophilic cells were positive for a smooth muscle actin. The granulomatous areas in the tumor were composed focally of epithelioid cells and lymphocytes. The epithelioid cells were negative for a smooth muscle actin. We diagnosed this case as an angioleiomyoma with epithelioid granuloma. Malignant tumors with granulomatous change have sometimes been reported in the literature, but benign tumors with epithelioid granuloma, such as the present one, are rare. We thought that epithelioid cell granuloma might transform to angioleiomyoma through the action of IL-1 released from vascular smooth muscle cells. PMID- 22059074 TI - Complete Healing of a Giant Wart in a Severely Immune-Compromised Patient with HIV Infection Treated with Acupuncture. AB - Giant warts are infrequent dermatological viral infections caused by Papillomavirus (HPV) in immune-compromised patients. Treatment may often be difficult and unsatisfactory, either by surgery or cytotoxic agents, because of poor immune control of viral activity in such hosts. Here we report on the case of a patient with advanced and persistent immune suppression caused by HIV disease, who developed a monstrous wart covering the entirety of the radial district of his right hand. He was completely healed after a long treatment with traditional Chinese acupuncture, in spite of minimal immune recovery induced by efficacious antiretroviral therapy. To the best of our knowledge, therefore, the present report may be the first direct clinical evidence that acupuncture may be effective in the treatment of cutaneous warts also in HIV-infected patients. PMID- 22059075 TI - Targeting GIRK Channels for the Development of New Therapeutic Agents. AB - G protein-coupled inward rectifier K(+) (GIRK) channels represent novel targets for the development of new therapeutic agents. GIRK channels are activated by a large number of G protein-coupled receptors (GPCRs) and regulate the electrical activity of neurons, cardiac myocytes, and beta-pancreatic cells. Abnormalities in GIRK channel function have been implicated in the patho-physiology of neuropathic pain, drug addiction, cardiac arrhythmias, and other disorders. However, the pharmacology of these channels remains largely unexplored. In this paper we describe the development of a screening assay for identifying new modulators of neuronal and cardiac GIRK channels. Pituitary (AtT20) and cardiac (HL-1) cell lines expressing GIRK channels were cultured in 96-well plates, loaded with oxonol membrane potential-sensitive dyes and measured using a fluorescent imaging plate reader. Activation of the endogenous GPCRs in the cells caused a rapid, time-dependent decrease in the fluorescent signal; indicative of K(+) efflux through the GIRK channels (GPCR stimulation versus control, Z'-factor = 0.5-0.7). As expected this signal was inhibited by addition of Ba(2+) and the GIRK channel toxin tertiapin-Q. To test the utility of the assay for screening GIRK channel blockers, cells were incubated for 5 min with a compound library of Na(+) and K(+) channel modulators. Ion transporter inhibitors such as 5-(N,N hexamethylene)-amiloride and SCH-28080 were identified as blockers of the GIRK channel at sub-micromolar concentrations. Thus, the screening assay will be useful for expanding the limited pharmacology of the GIRK channel and in developing new agents for the treatment of GIRK channelopathies. PMID- 22059076 TI - Engineering Parvalbumin for the Heart: Optimizing the Mg Binding Properties of Rat beta-Parvalbumin. AB - Parvalbumin (PV), an EF-hand protein family member, is a delayed calcium buffer that exchanges magnesium for calcium to facilitate fast skeletal muscle relaxation. Genetic approaches that express parvalbumin in the heart also enhance relaxation and show promise of being therapeutic against various cardiac diseases where relaxation is compromised. Unfortunately, skeletal muscle PVs have very slow rates of Ca(2+) dissociation and are prone to becoming saturated with Ca(2+), eventually losing their buffering capability within the constantly beating heart. In order for PV to have a more therapeutic potential in the heart, a PV with faster rates of calcium dissociation and high Mg(2+) affinity is needed. We demonstrate that at 35 degrees C, rat beta-PV has an ~30-fold faster rate of Ca(2+) dissociation compared to rat skeletal muscle alpha-PV, and still possesses a physiologically relevant Ca(2+) affinity (~100 nM). However, rat beta PV will not be a delayed Ca(2+) buffer since its Mg(2+) affinity is too low (~1 mM). We have engineered two mutations into rat beta-PV, S55D and E62D, when observed alone increase Mg(2+) affinity up to fivefold, but when combined increase Mg(2+) affinity ~13-fold, well within a physiologically relevant affinity. Furthermore, the Mg(2+) dissociation rate (172/s) from the engineered S55D, E62D PV is slow enough for delayed Ca(2+) buffering. Additionally, the engineered PV retains a high Ca(2+) affinity (132 nM) and fast rate of Ca(2+) dissociation (64/s). These PV design strategies hold promise for the development of new therapies to remediate relaxation abnormalities in different heart diseases and heart failure. PMID- 22059077 TI - Individual differences in audio-vocal speech imitation aptitude in late bilinguals: functional neuro-imaging and brain morphology. AB - An unanswered question in adult language learning or late bi and multilingualism is why individuals show marked differences in their ability to imitate foreign accents. While recent research acknowledges that more adults than previously assumed can still acquire a "native" foreign accent, very little is known about the neuro-cognitive correlates of this special ability. We investigated 140 German-speaking individuals displaying varying degrees of "mimicking" capacity, based on natural language text, sentence, and word imitations either in their second language English or in Hindi and Tamil, languages they had never been exposed to. The large subject pool was strictly controlled for previous language experience prior to magnetic resonance imaging. The late-onset (around 10 years) bilinguals showed significant individual differences as to how they employed their left-hemisphere speech areas: higher hemodynamic activation in a distinct fronto-parietal network accompanied low ability, while high ability paralleled enhanced gray matter volume in these areas concomitant with decreased hemodynamic responses. Finally and unexpectedly, males were found to be more talented foreign speech mimics. PMID- 22059078 TI - Improved Visual Cognition through Stroboscopic Training. AB - Humans have a remarkable capacity to learn and adapt, but surprisingly little research has demonstrated generalized learning in which new skills and strategies can be used flexibly across a range of tasks and contexts. In the present work we examined whether generalized learning could result from visual-motor training under stroboscopic visual conditions. Individuals were assigned to either an experimental condition that trained with stroboscopic eyewear or to a control condition that underwent identical training with non-stroboscopic eyewear. The training consisted of multiple sessions of athletic activities during which participants performed simple drills such as throwing and catching. To determine if training led to generalized benefits, we used computerized measures to assess perceptual and cognitive abilities on a variety of tasks before and after training. Computer-based assessments included measures of visual sensitivity (central and peripheral motion coherence thresholds), transient spatial attention (a useful field of view - dual task paradigm), and sustained attention (multiple object tracking). Results revealed that stroboscopic training led to significantly greater re-test improvement in central visual field motion sensitivity and transient attention abilities. No training benefits were observed for peripheral motion sensitivity or peripheral transient attention abilities, nor were benefits seen for sustained attention during multiple-object tracking. These findings suggest that stroboscopic training can effectively improve some, but not all aspects of visual perception and attention. PMID- 22059079 TI - Is reasoning in rats really unreasonable? Revisiting recent associative accounts. PMID- 22059080 TI - Individual Differences in Heart Rate Variability Predict the Degree of Slowing during Response Inhibition and Initiation in the Presence of Emotional Stimuli. AB - Response inhibition is a hallmark of executive control and crucial to support flexible behavior in a constantly changing environment. Recently, it has been shown that response inhibition is influenced by the presentation of emotional stimuli (Verbruggen and De Houwer, 2007). Healthy individuals typically differ in the degree to which they are able to regulate their emotional state, but it remains unknown whether individual differences in emotion regulation (ER) may alter the interplay between emotion and response inhibition. Here we address this issue by testing healthy volunteers who were equally divided in groups with high and low heart rate variability (HRV) during rest, a physiological measure that serves as proxy of ER. Both groups performed an emotional stop-signal task, in which negative high arousing pictures served as negative emotional stimuli and neutral low arousing pictures served as neutral non-emotional stimuli. We found that individuals with high HRV activated and inhibited their responses faster compared to individuals with low HRV, but only in the presence of negative stimuli. No group differences emerged for the neutral stimuli. Thus, individuals with low HRV are more susceptible to the adverse effects of negative emotion on response initiation and inhibition. The present research corroborates the idea that the presentation of emotional stimuli may interfere with inhibition and it also adds to previous research by demonstrating that the aforementioned relationship varies for individuals differing in HRV. We suggest that focusing on individual differences in HRV and its associative ER may shed more light on the dynamic interplay between emotion and cognition. PMID- 22059081 TI - Threat but not arousal narrows attention: evidence from pupil dilation and saccade control. AB - It has been shown that negative affect causes attentional narrowing. According to Easterbrook's (1959) influential hypothesis this effect is driven by the withdrawal motivation inherent to negative emotions and might be related to increases in arousal. We investigated whether valence-unspecific increases in physiological arousal, as measured by pupil dilation, could account for attentional narrowing effects in a cognitive control task. Following the presentation of a negative, positive, or neutral picture, participants performed a saccade task with a pro-saccade versus an anti-saccade instruction. The reaction time difference between pro- and anti-saccades was used to index attentional selectivity, and while pupil diameter was used as an index of physiological arousal. Pupil dilation was observed for both negative and positive pictures, which indicates increased physiological arousal. However, increased attentional selectivity was only observed following negative pictures. Our data show that motivational intensity effects on attentional narrowing can occur independently of physiological arousal effects. PMID- 22059082 TI - Mismatch brain response to speech sound changes in rats. AB - Understanding speech is based on neural representations of individual speech sounds. In humans, such representations are capable of supporting an automatic and memory-based mechanism for auditory change detection, as reflected by the mismatch negativity (MMN) of event-related potentials. There are also findings of neural representations of speech sounds in animals, but it is not known whether these representations can support the change detection mechanism analogous to that underlying the MMN in humans. To this end, we presented synthesized spoken syllables to urethane-anesthetized rats while local field potentials were epidurally recorded above their primary auditory cortex. In an oddball condition, a deviant stimulus /ga/ or /ba/ (probability 1:12 for each) was rarely and randomly interspersed between frequently presented standard stimulus /da/ (probability 10:12). In an equiprobable condition, 12 syllables, including /da/, /ga/, and /ba/, were presented in a random order (probability 1:12 for each). We found evoked responses of higher amplitude to the deviant /ba/, albeit not to /ga/, relative to the standard /da/ in the oddball condition. Furthermore, the responses to /ba/ were higher in amplitude in the oddball condition than in the equiprobable condition. The findings suggest that anesthetized rat's brain can form representations of human speech sounds, and that these representations can support the memory-based change detection mechanism analogous to that underlying the MMN in humans. Our findings show a striking parallel in speech processing between humans and rodents and may thus pave the way for feasible animal models of memory-based change detection. PMID- 22059083 TI - Language-mediated visual orienting behavior in low and high literates. AB - The influence of formal literacy on spoken language-mediated visual orienting was investigated by using a simple look and listen task which resembles every day behavior. In Experiment 1, high and low literates listened to spoken sentences containing a target word (e.g., "magar," crocodile) while at the same time looking at a visual display of four objects (a phonological competitor of the target word, e.g., "matar," peas; a semantic competitor, e.g., "kachuwa," turtle, and two unrelated distractors). In Experiment 2 the semantic competitor was replaced with another unrelated distractor. Both groups of participants shifted their eye gaze to the semantic competitors (Experiment 1). In both experiments high literates shifted their eye gaze toward phonological competitors as soon as phonological information became available and moved their eyes away as soon as the acoustic information mismatched. Low literates in contrast only used phonological information when semantic matches between spoken word and visual referent were not present (Experiment 2) but in contrast to high literates these phonologically mediated shifts in eye gaze were not closely time-locked to the speech input. These data provide further evidence that in high literates language mediated shifts in overt attention are co-determined by the type of information in the visual environment, the timing of cascaded processing in the word- and object-recognition systems, and the temporal unfolding of the spoken language. Our findings indicate that low literates exhibit a similar cognitive behavior but instead of participating in a tug-of-war among multiple types of cognitive representations, word-object mapping is achieved primarily at the semantic level. If forced, for instance by a situation in which semantic matches are not present (Experiment 2), low literates may on occasion have to rely on phonological information but do so in a much less proficient manner than their highly literate counterparts. PMID- 22059084 TI - The influence of expertise in simultaneous interpreting on non-verbal executive processes. AB - This study aimed to explore non-verbal executive processes in simultaneous interpreters. Simultaneous interpreters, bilinguals without any training in simultaneous interpreting, and control monolinguals performed the Wisconsin card sorting task (WCST; Experiment 1) and the Simon task (Experiment 2). Performance on WCST was thought to index cognitive flexibility while Simon task performance was considered an index of inhibitory processes. Simultaneous interpreters outperformed bilinguals and monolinguals on the WCST by showing reduced number of attempts to infer the rule, few errors, and few previous-category perseverations. However, simultaneous interpreters presented Simon effects similar to those found in bilinguals and monolinguals. Together, these results suggest that experience in interpreting is associated with changes in control processes required to perform interpreting tasks. PMID- 22059085 TI - Status and mating success amongst visual artists. AB - Geoffrey Miller has hypothesized that producing artwork functions as a mating display. Here we investigate the relationship between mating success and artistic success in a sample of 236 visual artists. Initially, we derived a measure of artistic success that covered a broad range of artistic behaviors and beliefs. As predicted by Miller's evolutionary theory, more successful male artists had more sexual partners than less successful artists but this did not hold for female artists. Also, male artists with greater artistic success had a mating strategy based on longer term relationships. Overall the results provide partial support for the sexual selection hypothesis for the function of visual art. PMID- 22059086 TI - Decision-making based on emotional images. AB - The emotional outcome of a choice affects subsequent decision making. While the relationship between decision making and emotion has attracted attention, studies on emotion and decision making have been independently developed. In this study, we investigated how the emotional valence of pictures, which was stochastically contingent on participants' choices, influenced subsequent decision making. In contrast to traditional value-based decision-making studies that used money or food as a reward, the "reward value" of the decision outcome, which guided the update of value for each choice, is unknown beforehand. To estimate the reward value of emotional pictures from participants' choice data, we used reinforcement learning models that have successfully been used in previous studies for modeling value-based decision making. Consequently, we found that the estimated reward value was asymmetric between positive and negative pictures. The negative reward value of negative pictures (relative to neutral pictures) was larger in magnitude than the positive reward value of positive pictures. This asymmetry was not observed in valence for an individual picture, which was rated by the participants regarding the emotion experienced upon viewing it. These results suggest that there may be a difference between experienced emotion and the effect of the experienced emotion on subsequent behavior. Our experimental and computational paradigm provides a novel way for quantifying how and what aspects of emotional events affect human behavior. The present study is a first step toward relating a large amount of knowledge in emotion science and in taking computational approaches to value-based decision making. PMID- 22059088 TI - Differentiation of Meat Samples from Domestic Horses (Equus caballus) and Asiatic Wild Asses (Equus hemionus) Using a Species-Specific Restriction Site in the Mitochondrial Cytochrome b Region. AB - Recent studies suggest that Asiatic wild asses (Equus hemionus) are being increasingly poached in a commercial fashion. Part of the meat is believed to reach the meat markets in the capital Ulaanbaatar. To test this hypothesis, we collected 500 meat samples between February and May 2006. To differentiate between domestic horse (Equus caballus) and wild ass meat, we developed a restriction fragment length polymorphism (RFLP) assay based on the polymerase chain reaction (PCR). We amplified and sequenced a cytochrome b fragment (335 bp) and carried out a multialignment of the generated sequences for the domestic horse, the Asiatic wild ass, the domestic donkey (Equus asinus) and the Przewalski's horse (Equus ferus przewalskii). We detected a species-specific restriction site (AatII) for the Asiatic wild ass, resulting in a specific restriction fragment length polymorphism (RFLP) band pattern. This RFLP assay represents a rapid and cost-effective method to detect wild ass meat. All of the 500 meat samples we collected and analysed within this pilot project proved to be domestic horsemeat as declared by the sales people. Thus, either the assumption that wild ass meat is sold as "cheap horse meat" is wrong, or we picked the wrong markets, products or season. PMID- 22059087 TI - Comparative and functional genomics of legionella identified eukaryotic like proteins as key players in host-pathogen interactions. AB - Although best known for its ability to cause severe pneumonia in people whose immune defenses are weakened, Legionella pneumophila and Legionella longbeachae are two species of a large genus of bacteria that are ubiquitous in nature, where they parasitize protozoa. Adaptation to the host environment and exploitation of host cell functions are critical for the success of these intracellular pathogens. The establishment and publication of the complete genome sequences of L. pneumophila and L. longbeachae isolates paved the way for major breakthroughs in understanding the biology of these organisms. In this review we present the knowledge gained from the analyses and comparison of the complete genome sequences of different L. pneumophila and L. longbeachae strains. Emphasis is given on putative virulence and Legionella life cycle related functions, such as the identification of an extended array of eukaryotic like proteins, many of which have been shown to modulate host cell functions to the pathogen's advantage. Surprisingly, many of the eukaryotic domain proteins identified in L. pneumophila as well as many substrates of the Dot/Icm type IV secretion system essential for intracellular replication are different between these two species, although they cause the same disease. Finally, evolutionary aspects regarding the eukaryotic like proteins in Legionella are discussed. PMID- 22059089 TI - Protease Activity and the Role of the Endothelial Glycocalyx in Inflammation. AB - A new paradigm for governance of leukocyte-endothelium (WBC-EC) adhesion during the inflammatory process is presented in which shedding of the endothelial glycocalyx exposes adhesion molecules on the EC surface, which promotes WBC-EC adhesion. It is postulated that the effector of this shedding is the activation of extracellular proteases, one of which may be a member of the matrix metalloproteinase (MMP) family of zinc dependent endopetidases. This model for the role of the glycocalyx as a barrier to WBC-EC adhesion includes the additional participation of normally active extracellular proteolytic enzymes, i.e. sheddases, which may cleave proteoglycans or activate lyases that cleave GAG chains in the glycocalyx. In support of this hypothesis, studies are examined which have established the concurrent activation of MMP proenzymes on the EC surface, shedding of the glycocalyx, and enhanced WBC-EC adhesion. PMID- 22059090 TI - Optofluidic Microsystems for Chemical and Biological Analysis. AB - Optofluidics - the synergistic integration of photonics and microfluidics - has recently emerged as a new analytical field that provides a number of unique characteristics for enhanced sensing performance and simplification of microsystems. In this review, we describe various optofluidic architectures developed in the past five years, emphasize the mechanisms by which optofluidics enhances bio/chemical analysis capabilities, including sensing and the precise control of biological micro/nanoparticles, and envision new research directions to which optofluidics leads. PMID- 22059091 TI - An Initial Psychometric Evaluation of the CBCL 6-18 in a Sample of Youth with Autism Spectrum Disorders. AB - Individuals with an autism spectrum disorder (ASD) often present with co occurring emotional and behavioral disorders (EBD). The Child Behavior Checklist 6-18 (CBCL; Achenbach & Rescorla, 2001) is an EBD measure that contains several norm-referenced scales derived through factor analysis of data from the general pediatric population. The psychometric properties of this widely used and well researched measure have not been evaluated in samples of youth with ASD. This study evaluated the CBCL's internal structure, scale reliability, criterion related validity, and diagnostic accuracy using archival data from a well characterized sample of youth with ASD (N = 122). Confirmatory factor analyses supported the unidimensionality of the CBCL's syndrome scales and its Internalizing-Externalizing factor structure. Significance tests indicated that many scales discriminated between two subgroups: a group of individuals with ASD+EBD and a group with ASD alone. Diagnostic accuracy analyses indicated that the CBCL had good sensitivity but low specificity for detecting co-occurring disorders. Results supported the use of the CBCL in conjunction with other clinical data when assessing for EBD in youth with ASD. PMID- 22059092 TI - TACTILE RESPONSIVENESS PATTERNS AND THEIR ASSOCIATION WITH CORE FEATURES IN AUTISM SPECTRUM DISORDERS. AB - Autism spectrum disorders (ASD) are often associated with aberrant responses to sensory stimuli, which are thought to contribute to the social, communication, and repetitive behavior deficits that define ASD. However, there are few studies that separate aberrant sensory responses by individual sensory modality to assess modality-specific associations between sensory features and core symptoms. Differences in response to tactile stimuli are prevalent in ASD, and tactile contact early in infancy is a foundation for the development of social and communication skills affected by ASD. We assessed the association between three aberrant patterns of tactile responsiveness (hyper-responsiveness, hypo responsiveness, sensory seeking) and core symptoms of ASD. Both sensory and core features were measured with converging methods including both parent-report and direct observation. Our results demonstrate that for the tactile modality, sensory hypo-responsiveness correlates strongly with increased social and communication impairments, and to a lesser degree, repetitive behaviors. Sensory seeking was found to correlate strongly with social impairment, nonverbal communication impairment, and repetitive behaviors. Surprisingly, tactile hyper responsiveness did not significantly correlate with any core features of ASD. This differential association between specific tactile processing patterns and core features provides an important step in defining the significance of sensory symptoms in ASD, and may be useful in the development of sensory-based approaches for early detection and intervention. PMID- 22059093 TI - Risk Factors of Non-Hodgkin Lymphoma. AB - INTRODUCTION: Despite decades of intensive research, Non-Hodgkin Lymphoma (NHL) remains poorly understood and is largely incurable. NHL is a heterogeneous group of malignancies with multiple subtypes, each of which has distinct morphologic, immunophenotypic, and clinical features. Identifying the risk factors for NHL may improve our understanding of the underlying biological mechanisms and have an impact on clinical practice. AREAS COVERED: This article provides a review of several aspects of NHL, including epidemiology and subtype classification, clinical, environmental, genetic, and genomic risk factors identified for etiology and prognosis, and available statistical and bioinformatics tools for identification of genetic and genomic risk factors from the analysis of high throughput studies. EXPERT OPINION: Multiple clinical and environmental risk factors have been identified. However, they have failed to provide practically effective prediction. Genetic and genomic risk factors identified from high throughput studies have suffered a lack of reproducibility. The identification of genetic/genomic risk factors demands innovative statistical and bioinformatics tools. Although multiple analysis methods have been developed, there is still room for improvement. There is a critical need for well-designed, prospective, large-scale pangenomic studies. PMID- 22059095 TI - Effects of school reformon education and labor market performance: Evidence from Chile's universal voucher system. AB - This paper studies the effects of school reform in Chile, which adopted a nationwide school voucher program along with school decentralization reforms in 1981. Since then, Chile has had a relatively unregulated, competitive market in primary and secondary education. It therefore provides a unique setting in which to study how these reforms affected school attainment and labor market outcomes. This paper develops and estimates a dynamic model of school attendance and work decisions using panel data from the 2002 and 2004 waves of the Encuesta de Proteccion Social survey. Some individuals in the sample completed their schooling before the voucher reforms were introduced, while others had the option of using the vouchers over part or all of their schooling careers. The impacts of the voucher reform are identified from differences in the schooling and work choices made and earnings returns received by similar aged individuals who were differentially exposed to the voucher system. Simulations based on the estimated model show that the voucher reform significantly increased the demand for private subsidized schools and decreased the demand for both public and nonsubsidized private schools. It increased high school (grades 9-12) graduation rates by 3.6 percentage points and the percentage completing at least two years of college by 2.6 percentage points. Individuals from poor and non-poor backgrounds on average experienced similar schooling attainment gains. The reform also increased lifetime utility and modestly reduced earnings inequality. PMID- 22059094 TI - Testing for Rheumatological Diagnoses in Children. AB - Paediatricians often order laboratory and radiological tests to identify children with potential rheumatological disease prior to subspeciality referral. However, the pattern of testing suggests inadequate understanding of their diagnostic utility and limitations. Herein we will address some of the most common rheumatological diagnoses encountered in the subspeciality clinic - juvenile idiopathic arthritis (JIA), juvenile spondyloarthritis (JSpA) and systemic lupus erythematosus (SLE), and related connective tissue diseases - and the tests most frequently ordered to diagnose them: anti-nuclear antibodies (ANA), rheumatoid factor (RF), human leukocyte antigen (HLA)-B27 and radiological tests. This article will highlight the sensitivity, specificity and positive predictive value of the tests. In general, none of these tests were appropriate to use as rheumatological 'screens', as no individual test was diagnostic. Specific tests should be ordered only when there is a high clinical index of suspicion for a particular disease entity. Greater understanding of a test's diagnostic utility should decrease unnecessary testing, anxiety and expense and aid in interpretation. PMID- 22059096 TI - Applause and congratulations. PMID- 22059097 TI - Report on the international Primary Neurosurgical Life Support course in the eighth Asian Congress of Neurological Surgeons in Kuala Lumpur, Malaysia. AB - On November 22, 2010, a simulation-based hands-on education course for medical staff in the neurosurgical fields was held in 8(th) Asian Congress of Neurological Surgeons (ACNS) in Kuala Lumpur, Malaysia. The present education course called Primary Neurosurgical Life Support (PNLS) course had been started by the Japan Society of Neurosurgical Emergency since 2008. This report summarizes the international version of PNLS course in 8(th) ACNS. PMID- 22059098 TI - Progress of women in neurosurgery. AB - Despite advances in issues related to gender equity, barriers to recruiting and retaining women in neurosurgery continue to exist. At the same time, the overall projected shortage of neurosurgeons suggests that women will be vital to the long term success of the field. Attracting women to neurosurgery can capitalize on strategies, such as mentoring, teaching leadership and negotiating skills, and job sharing or dual training tracks to name a few, that would benefit both men and women passionate about pursuing neurosurgery. Ultimately, personal and institutional accountability must be evaluated to ensure that the best and brightest candidates, regardless of gender, are recruited to neurosurgical programs to promote the health of our challenging but most satisfying profession. PMID- 22059099 TI - Surgical Strategies and outcomes for distal anterior cerebral arteries aneurysms. AB - BACKGROUND: Distal anterior cerebral artery (DACA) aneurysms are rare and their surgical treatment presents some unique difficulties. In this report, we present our experience of cases with DACA aneurysms. MATERIALS AND METHODS: Among 80 patents with cerebral aneurysm operated on in the three-year period, 15 patients (18.75%) had DACA aneurysms, who were studied retrospectively. We analyze the specific clinical and radiological features, surgical strategies and prognostic factors affecting the surgical outcomes of these DACA aneurysms. RESULTS: There were 10 male and 5 female patients harboring 16 DACA aneurysms. All patients presented with subarachnoid hemorrhage, 11 patients (73%) had intracerebral hematoma in their initial CT scan and four of them had associated intraventricular hemorrhage. Thirteen of the ruptured DACA aneurysms (86%) were small in size (less than 7 mm in diameter). Three patients (20%) had other associate aneurysms. In 14 patients (93%), a unilateral interhemispheric approach was used in their treatment, while pterional approach was used in one patient. Eleven patients (73%) had favorable outcomes and only one patient (7%) died. The follow-up data suggested that poor admission grade and initial Intracerebral hematoma (ICH) on brain scan portend an unfavorable prognosis. CONCLUSIONS: DACA aneurysms are usually small even when ruptured, they are usually associated with ICH more frequently than intracranial aneurysms in other locations. They should be aggressively treated even if very small because of their tendency to early rupture. PMID- 22059100 TI - Surgical treatment of ventral and ventrolateral intradural extramedullary tumors of craniovertebral and upper cervical localization. AB - BACKGROUND: Surgical treatment of extramedullary craniovertebral and upper cervical tumors differs essentially, depending on the peculiarities of their localization. MATERIALS AND METHODS: In the Spinal Department of the Institute of Neurosurgery during the period from 2000 to 2010, 96 patients with ventral and ventrolateral intradural extramedullary craniovertebral tumors and tumors of upper cervical localization were examined and operated. RESULTS: The patients were distributed as follows. Tumors of the craniovertebral localization: These are neoplasms spreading in rostral direction up to the boundary of the lower third of the clivus and in caudal direction up to the upper edge body of the axis (C0-C1) - 12 patients; tumors at the C1-C2 level: 28 patients; and tumors at the C1-C2-C3 level: 56 patients. The tumors were divided into ventral (60) and ventrolateral (36). CONCLUSION: Therefore, the adequate choice of a surgical approach first depends on the localization of the tumor, its size and the extent to which it has spread. In most cases of extramedullary ventrolateral tumors of craniovertebral and upper cervical localization, far lateral and posterolateral approaches are the most optimum and the least traumatic. The extreme lateral approach is advisable in cases of big size ventral craniovertebral tumors. PMID- 22059101 TI - Role of magnesium sulfate in aneurysmal subarachnoid hemorrhage management: A meta-analysis of controlled clinical trials. AB - BACKGROUND: There has been longstanding controversy over the use of magnesium sulfate infusion in the medical management of aneurysmal subarachnoid hemorrhage (SAH). Several clinical trials evaluating the beneficial effects of magnesium on cerebral vasospasm and their poor outcome have been published. However, results from the majority of these studies have been inconclusive. This meta-analysis was performed to evaluate the effectiveness of magnesium on patient outcomes after aneurysmal SAH. MATERIALS AND METHODS: PubMed and the Cochrane library were searched for controlled clinical trials assessing the efficacy of magnesium sulfate infusion after aneurysmal SAH. Eight studies consisting of 936 patients were included. RESULTS: There was a decreased risk of poor outcome at 3-6 months after SAH in magnesium treatment groups when compared to placebo [0.78 (95% CI 0.66-0.93)]. Poor outcome was defined as severe disability, persistent vegetative state, or death, as measured by the Glasgow outcome scale (GOS), extended Glasgow outcome scale (GOSE) or modified Rankin scale (mRS). The risk of mortality after SAH was unaffected by magnesium treatment [RR 0.68 (95% CI 0.58-1.27)]. CONCLUSION: Magnesium sulfate infusion decreases risk of poor outcome after aneurysmal SAH. Current studies in the literature do not suggest a role for magnesium sulfate in mortality reduction after SAH. PMID- 22059102 TI - Advances in neurosurgery: The Fujita Health University experience. AB - In a world with rapidly changing technologies in the field of neurosurgery, Japan leads the world in many subspecialities like vascular neurosurgery. Apart from this, neuro-oncology and spinal surgeries are also among the premium quality operations performed in the region. I would like to share my experience of spending 3 months at the Fujita Health University, Nagoya, Japan, and the rich expertise and technologies encountered during the period, which made me understand Neurosurgery in a better way. PMID- 22059103 TI - Low velocity penetrating head injury with impacted foreign bodies in situ. AB - Penetrating head injury is a potentially life-threatening condition. Penetrating head injuries with impacted object (weapon) are rare. The mechanism of low velocity injury is different from high velocity missile injury. Impacted object (weapon) in situ poses some technical difficulties in the investigation and management of the victims, and if the anticipated problems are not managed properly, they may give rise to serious consequences. The management practice of eight patients with impacted object in situ in context of earlier reported similar cases in literature is presented. PMID- 22059104 TI - Transvenous embolization in spontaneous direct carotid-cavernous fistula in childhood. AB - Carotid cavernous fistula (CCF) is an abnormal arteriovenous communication in the cavernous sinus. Direct CCF results from a tear in the intracavernous carotid artery. Typically, it has a high flow and usually presents with oculo-orbital venous congestive features such as exophthalmos, chemosis, and sometimes oculomotor or abducens cranial nerve palsy. Indirect CCF generally occurs spontaneously with subtle signs. We report a rare case of spontaneous direct CCF in childhood who did not have the usual history of craniofacial trauma or connective tissue disorder but presented with progressive chemosis and exophthalmos of the right eye. This report aims also to describe the safety and success of transvenous embolization with coils of the superior ophthalmic vein and cavernous sinus through the inferior petrosal sinus. PMID- 22059105 TI - Intrathecal baclofen therapy in severe head injury, first time in Nepal, a technique suitable for underdeveloped countries. AB - Intrathecal baclofen (ITB) has been found to be helpful not only for spasticity but also for unconsciousness in a vegetative patient. This is the first case of ITB in Nepal, and here we discuss the effectiveness of ITB for spasticity in a patient in vegetative state. We also discuss about a simple technique for ITB used in Nepal where baclofen pump is not available. Here, we present a case of a 40-year-old male patient who had severe head injury with diffuse axonal injury treated conservatively. He went on to a vegetative state and subsequently developed severe spasticity of all the limbs. ITB was started under the guidance of one of the authors , Prof. Taira. Baclofen was injected to the spinal intrathecal space through a catheter which is used for spinal anesthesia. Spasticity improved significantly and his higher mental function also showed signs of improvement. He finally became fully conscious and well oriented. ITB is very useful in cases of severe spasticity and vegetative condition, a state of unconsciousness lasting longer than a few weeks. Even with a simple technique in the absence of baclofen pump, ITB can be used with its optimum effect. PMID- 22059106 TI - Sexual Risk Behaviors with Female and Male Partners Met in Different Sexual Venues Among Non-Gay-Identified, Non-Disclosing MSMW. AB - Despite considerable interest in the sexual behavior of non-disclosing men who have sex with men and women (MSMW), little is known about where they meet their male and female partners and whether their sexual risk behavior differs with partners met in different sexual venues (e.g., bars, Internet, parks). These issues were examined among 46 non-gay-identified MSMW who had not disclosed their same-sex behavior to female partners (i.e., men on the "down low"). The prevalence of unprotected vaginal sex was nearly identical with women met in bars/clubs as with women met through friends, work, or the neighborhood. In contrast, the prevalence of unprotected anal sex was higher with male partners met on the Internet, in bars/clubs, and through friends/work/neighborhood as compared with partners met in parks/restrooms or gyms. This is largely due to MSMW avoiding anal sex in parks, restrooms, and gyms, in favor of oral sex. These findings provide important insights into the role of venues on sexual risk and the locations where risk reduction interventions for MSMW may be provided. PMID- 22059107 TI - Fasting Triglyceride Concentrations are Associated with Early Mortality Following Antiretroviral Therapy in Zambia. AB - BACKGROUND: In developing countries, 8 to 71% of patients initiating highly active antiretroviral therapy (HAART) die within the first year of treatment. Apart from baseline CD4 count, viral load, hemoglobin, BMI and stage of the disease, there may be other variables that contribute to AIDS-related mortality. We investigated the potential role of nutrition, lipids and insulin resistance related phenotypes in predicting early mortality. METHODS: We recruited 210 HAART-naive HIV/AIDS patients in Lusaka, Zambia. Dietary intake, anthropometric measurements, fasting serum insulin, glucose, and lipid profiles were assessed at baseline. Mortality was assessed after 90 days of follow-up. We used logistic regression models to identify variables associated with mortality. RESULTS: The mean+/-SD for age, BMI and CD4 count at baseline were 34+/-7.4 y, 20+/-3 kg/m(2) and 138+/-52 cells/MUL, respectively. Sixteen patients (7.6%) died during follow up. Triglyceride concentrations were associated with increased mortality [odds ratio (OR) for 1 mmol/L increase in triglyceride concentration=2.51; 95% CI: 1.34 4.71]. This association remained significant (OR=3.24; 95% CI: 1.51-6.95) after adjusting for age, gender, smoking, alcohol use, total cholesterol, BMI, CD4 count and n3 fatty acid intake. Apart from higher n3 fat intake which was inversely associated with mortality (survivors: 1.81+/-0.99% total energy/day vs. non-survivors 1.28+/-0.66% energy/day, P=0.04), there were no other macronutrients associated with mortality. CONCLUSION: Triglyceride concentrations at the time of initiating HAART are independently associated with increased risk for early mortality. If this association is confirmed in larger studies, assessment of triglycerides could become part of routine care of HIV patients initiating HAART in developing countries. PMID- 22059108 TI - Budd-Chiari syndrome management: Lights and shadows. AB - Budd-Chiari syndrome (BCS) is a rare disease whose management should follow a step by step strategy. Anticoagulation and medical therapy should be the first line treatment. Revascularization or TIPS are indicated in case of no response to medical therapy. OLT should be indicated as a rescue therapy and anticoagulation be started soon after OLT. However, no clear indication can actually be given about the timing of different treatments. Moreover, there is some concern about treatment of some subgroup of patients, especially regarding the risk of recurrence after liver transplantation. The topic of this paper is to critically review the actual knowledge of BCS management. PMID- 22059109 TI - Role of ezetimibe in non-alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis, advanced fibrosis and inflammatory changes. Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes. The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1). Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol. Ezetimibe exerts beneficial effects on several metabolic variables. Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers. The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients. Our group investigated the ezetimibe orlistat combination treatment in overweight and obese patients with hypercholesterolemia, with beneficial effects on NAFLD biochemical markers. These results are promising for patients with NAFLD, who usually have increased cardiovascular disease risk and need a multifactorial treatment. However, it should be mentioned that most results are from animal studies and, although modest elevation of liver function tests may raise the suspicion of NAFLD, none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy. PMID- 22059110 TI - Bee sting therapy-induced hepatotoxicity: A case report. AB - The use of bee venom as a therapeutic agent for the relief of joint pains dates back to Hippocrates, and references to the treatment can be found in ancient Egyptian and Greek medical writings as well. Also known as apitherapy, the technique is widely used in Eastern Europe, Asia, and South America. The beneficial effects of bee stings can be attributed to mellitinin, an anti inflammatory agent, known to be hundred times stronger than cortisone. Unfortunately, certain substances in the bee venom trigger allergic reactions which can be life threatening in a sensitized individual. Multiple stings are known to cause hemolysis, kidney injury, hepatotoxicity and myocardial infarction. The toxicity can be immediate or can manifest itself only weeks after the exposure. We describe hepatotoxicity in a 35-year-old female, following bee sting therapy for multiple sclerosis. She presented to our clinic 3 wk after therapy with a history of progressive jaundice. The patient subsequently improved, and has been attending our clinic now for the last 9 mo. PMID- 22059111 TI - A histologically proven case of progressive liver sarcoidosis with variceal rupture. AB - Sarcoidosis is a chronic multi-systemic granulomatous disease, and liver involvement frequently occurs. in most cases, no evidence of liver dysfunction is observed, and portal hypertension due to sarcoid liver diseases is a rareoccurrence. Moreover, no case of liver sarcoidosis has ever been reported with confirmation of the disease progression. Herein we describe a patient having hepatic sarcoidosis with severe portal hypertension and liver dysfunction. The diagnosis was histologically confirmed from granulomatous status to established liver cirrhosis over 10 years. A 46-year-old woman developed massive hematemesis due to the rupture of gastric cardial varices. She underwent emergency endoscopic injection sclerotherapy, and clear evidence of chronic hepatic failure. Twelve years ago, she was diagnosed as having sarcoidosis with respiratory clinicalsymptoms. Liver biopsy revealed asymptomatic incidental granulomas without fibrosis development. After a couple of years, features of liver dysfunction were manifest and progressed. Ten years after the first biopsy, a second liver biopsy was performed, and well established dense fibrosis was revealed. Although significant liver dysfunction with portal hypertension is rarely seen in sarcoidosis, this case indicates that we have to consider the possibility that sarcoidosis may cause end-stage liver cirrhosis. PMID- 22059112 TI - Revisiting acute liver injury associated with herbalife products. AB - In the November 27, 2010 issue of the World Journal of Hepatology (WJH), three case reports were published which involved patients who had consumed various dietary supplements and conventional foods generally marketed as weight loss products. The reference to Herbalife products as contaminated and generally comparable to all dietary supplements or weight loss products is not scientifically supported. The authors provided an insufficient amount of information regarding patient histories, concomitant medications and other compounds, dechallenge results, and product specifications and usage. This information is necessary to fully assess the association of Herbalife products in the WJH case reports. Therefore, the article does not objectively support a causal relationship between the reported cases of liver injury and Herbalife products or ingredients. PMID- 22059113 TI - Mechanism of Inhibition of the GluA2 AMPA Receptor Channel Opening: the Role of 4 Methyl versus 4-Carbonyl Group on the Diazepine Ring of 2,3-Benzodiazepine Derivatives. AB - 2,3-Benzodiazepine derivatives are synthesized as drug candidates for a potential treatment of various neurodegenerative diseases involving the excessive activity of AMPA receptors. Here, we describe a rapid kinetic investigation of the mechanism of inhibition of the GluA2Q(flip) AMPA receptor channel opening by two 2,3-benzodiazepine derivatives, i.e. the prototypic 2,3-benzodiazepine compound GYKI 52466 [(1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3 benzodiazepine)] and 1-(4-aminophenyl)-3,5-dihydro-7,8-methylenedioxy-4H-2,3 benzodiazepin-4-one (BDZ-2). GYKI 52466 and BDZ-2 are structurally similar in that the 4-methyl group in the diazepine ring of GYKI 52466 is replaced by a carbonyl group, yielding BDZ-2. Using a laser-pulse photolysis technique with ~60 MUs time resolution, we characterize the effect of the two compounds individually on the channel-opening process of the GluA2Q(flip) receptor expressed in HEK-293 cells. We find that BDZ-2 preferentially inhibits the open-channel state, whereas GYKI 52466 is more selective for the closed-channel state of the GluA2Q(flip) receptors. Each inhibitor binds independently to its own noncompetitive site, yet the two sites do not interact allosterically. The significance of these results in the context of both the structure-activity relationship and the properties of the GluA2Q(flip) receptor channels is presented. PMID- 22059114 TI - Phase-shift, stimuli-responsive drug carriers for targeted delivery. AB - The intersection of particles and directed energy is a rich source of novel and useful technology that is only recently being realized for medicine. One of the most promising applications is directed drug delivery. This review focuses on phase-shift nanoparticles (that is, particles of submicron size) as well as micron-scale particles whose action depends on an external-energy triggered, first-order phase shift from a liquid to gas state of either the particle itself or of the surrounding medium. These particles have tremendous potential for actively disrupting their environment for altering transport properties and unloading drugs. This review covers in detail ultrasound and laser-activated phase-shift nano- and micro-particles and their use in drug delivery. Phase-shift based drug-delivery mechanisms and competing technologies are discussed. PMID- 22059115 TI - Neural correlates of emotion-cognition interactions: A review of evidence from brain imaging investigations. AB - Complex dynamic behaviour involves reciprocal influences between emotion and cognition. On the one hand, emotion is a "double-edged sword" that may affect various aspects of our cognition and behaviour, by enhancing or hindering them and exerting both transient and long-term influences. On the other hand, emotion processing is also susceptible to cognitive influences, typically exerted in the form of emotion regulation. Noteworthy, both of these reciprocal influences are subjective to individual differences that may affect the way we perceive, experience, and eventually remember emotional experiences, or respond to emotionally challenging situations. Understanding these relationships is critical, as unbalanced emotion-cognition interactions may lead to devastating effects, such as those observed in mood and anxiety disorders. The present review analyses the reciprocal relationships between emotion and cognition, based on evidence derived from brain imaging investigations focusing on three main topics: (1) the impact of emotion on cognition, (2) the impact of cognition on emotion, and (3) the role of individual differences in emotion-cognition interactions. This evidence will be discussed in the context of identifying aspects that are fundamental to understanding the mechanisms underlying emotion-cognition interactions in healthy functioning, and to understanding changes associated with affective disorders. PMID- 22059116 TI - Temperature-responsive biocompatible copolymers incorporating hyperbranched polyglycerols for adjustable functionality. AB - Temperature-triggered copolymers are proposed for a number of bio-applications but there is no ideal material platform, especially for injectable drug delivery. Options are needed for degradable biomaterials that not only respond to temperature but also easily accommodate linkage of active molecules. A first step toward realizing this goal is the design and synthesis of the novel materials reported herein. A multifunctional macromer, methacrylated hyperbranched polyglycerol (HPG-MA) with an average of one acrylate unit per copolymer, was synthesized and copolymerized with N-isopropylacrylamide (NIPAAm), hydroxyethyl methacrylate-polylactide (HEMAPLA) and acrylic acid (AAc). The potential to fully exploit the copolymers by modification of the multiple HPG hydroxyl groups will not be discussed here. Instead, this report focuses on the thermoresponsive, biocompatible, and degradation properties of the material. Poly(NIPAAm-co-HEMAPLA co-AAc-co-HPG-MA) displayed increasing lower critical solution temperatures (LCST) as the HPG content increased over a range of macromer ratios. For the copolymer with the maximum HPG incorporation (17%), the LCST was ~30 degrees C. In addition, this sample showed no toxicity when human uterine fibroid cells were co-cultured with the copolymer for up to 72 h. This copolymer lost approximately 92% of its mass after 17 hours at 37 degrees C. Thus, the reported biomaterials offer attractive properties for the design of drug delivery systems where orthogonally triggered mechanisms of therapeutic release in relatively short time periods would be attractive. PMID- 22059118 TI - Cranioplasty after decompressive craniectomy: An institutional audit and analysis of factors related to complications. AB - BACKGROUND: Although a relatively simple procedure, cranioplasties have been associated with high complication rates. Keeping this in perspective, we aimed to determine the factors associated with immediate and long-term complications of cranioplasties at our institution. METHODS: A retrospective review of patient records was carried out for patients having undergone reconstructive cranioplasties at our institution during the last 10 years (2001-2010). All case notes, records, and investigations were reviewed and the data were recorded in a predesigned questionnaire. Complications were recorded along with existing comorbids and measures taken for their prevention and management. Univariate and multivariate logistic regression analysis was performed to determine possible predictors of complications. RESULTS: A total of 96 patients with a mean age of 33 + 15 years were included in the study. Of the sample, 76% (n = 73) had no comorbids. The leading primary pathology was blunt traumatic brain injuries in 46% (n = 44), followed by cerebrovascular incidents in 24% (n = 23), penetrating traumatic brain injuries in 12% (n = 11), and tumors in 10% (n = 10) of cases, with 41% (n = 39) of patients requiring multiple craniotomies. In a mean follow up of 386 +/- 615 days, complications were noted in 36.5% (n = 35) of the patients. Twenty six percent of patients (n = 25) had minor complications which included breakthrough seizures (15.6%, n = 15), subgaleal collections (3.1%, n = 3), and superficial wound infections (3.1%, n = 3), whereas major complications (10.4% n = 10) included hydrocephalus (3.1%, n = 3), transient neurological deficits (3.1%, n = 3), and osteomyelitis (2.1%, n = 2). Univariate and multivariate analysis revealed External Ventricular Drain (EVD) placement and parietal flaps to be associated with complications. This could be explained by the fact that the patients requiring EVD usually have relatively severe head injuries, increasing the possibility of hydrocephalus. CONCLUSION: We have found a higher risk of complications of cranioplasty in patients who had EVD placement and removal prior to their constructive surgery. We however did not find any association between risks of complications in any other studied variable. We also did not find any association between intraoperative placement of subgaleal drains and postoperative risk of subgaleal fluid collections. Overall, our results are comparable with other reported series on cranioplasties. PMID- 22059117 TI - Approaches to Fungal Genome Annotation. AB - Fungal genome annotation is the starting point for analysis of genome content. This generally involves the application of diverse methods to identify features on a genome assembly such as protein-coding and non-coding genes, repeats and transposable elements, and pseudogenes. Here we describe tools and methods leveraged for eukaryotic genome annotation with a focus on the annotation of fungal nuclear and mitochondrial genomes. We highlight the application of the latest technologies and tools to improve the quality of predicted gene sets. The Broad Institute eukaryotic genome annotation pipeline is described as one example of how such methods and tools are integrated into a sequencing center's production genome annotation environment. PMID- 22059119 TI - Unilateral subfrontal approach to anterior communicating artery aneurysms: A review of 28 patients. AB - BACKGROUND: The pterional approach is the most common for AComm aneurysms, but we present a unilateral approach to a midline region for addressing the AComm complex. The pure subfrontal approach eliminates the lateral anatomic dissection requirements without sacrificing exposure. The subfrontal approach is not favored in the US compared to Asia and Europe. We describe our experience with the subfrontal approach for AComm aneurysms treated at a single institution. METHODS: We identified 28 patients treated for AComm aneurysms through the subfrontal approach. Patient records and imaging studies were reviewed. Demographics and case data, as well as clinical outcome at 6 weeks and 1 year were collected. RESULTS: Mean patient age was 48 (range 21-75) years and 64% suffered subarachnoid hemorrhage (SAH). All aneurysms were successfully clipped. Gyrus rectus was resected in 57% of cases, more commonly in ruptured cases. Intraoperative rupture occurred in 11% of cases. The average operative time was 171 minutes. There were two patient deaths. Ninety-two percent of patients had a Glasgow Outcome Scale (GOS) of 5 at 6 weeks. All unruptured patients had a GOS of 5. At 12 months, 96% of all patients had a GOS of 5. CONCLUSIONS: The subfrontal approach provides an efficient avenue to the AComm region, which reduces opening and closing friction but still yields a comprehensive operative window for access to the anterior communicating region. PMID- 22059120 TI - Treatment of aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysms by neurosurgeons in Colombia: A survey. AB - BACKGROUND: Trends in management of aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysms among neurosurgeons is very variable and had not been previously described in any Latin American country. This study was conducted to determine the preferences of Colombian neurosurgeons in pharmacologic, surgical, and endovascular management of patients with aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysms. METHODS: A survey based descriptive study was performed in a sample of members from the Colombian Association of Neurosurgery. Questions about pharmacologic, surgical, and endovascular management of aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysm were carried out. We calculated the mean and the standard deviation of the results obtained from the continuous variables. The results of the categorical variables are presented as percentages. RESULTS: The preference of medication with poor clinical evidence, such as magnesium sulfate, aspirin, statins, and anti-fibrinolytics was lower than 10%. The use of intravenous nimodipine and systemic glucocorticoids was as high as 31%. The availability of endovascular therapy was 69%. The indication for treatment of patients with unruptured intracranial aneurysms that required intervention was less than 13.8%. In patients with ruptured or unruptured intracranial aneurysms, coiling was the preferred method for exclusion. CONCLUSIONS: Reported compliance of evidence based clinical guidelines was similar to that described in developed countries, and even better. However, there is little agreement in treating patients with unruptured intracranial aneurysms. For other issues, the conducts reported by Colombian neurosurgeons are in accordance with the current guidelines. PMID- 22059121 TI - Ruptured cerebral aneurysm associated with a persistent primitive trigeminal artery variant. AB - BACKGROUND: Primitive trigeminal artery variants (PTAVs) are one of the rare persistent fetal anastomoses between the carotid and vertebrobasilar circulations. They originate from the internal carotid artery and join one of the cerebellar arteries instead of the basilar artery. CASE DESCRIPTION: We present an 82-year-old woman with subarachnoid hemorrhage due to a ruptured aneurysm originating at a PTAV. Three-dimensional computed tomography angiogram and cerebral angiography revealed bilateral PTAV and two aneurysms originating at the left PTAV. The proximal and distal aneurysms were saccular and fusiform, respectively. She underwent surgical treatment and her postoperative course was uneventful. CONCLUSION: Our case demonstrates that extremely rare cerebral aneurysms associated with PTAV can be addressed successfully by surgical intervention. PMID- 22059122 TI - Multiple non-branching dissecting aneurysms of the mid-basilar trunk presenting with sequential subarachnoid hemorrhages. AB - OBJECTIVE: We describe a rare case of a patient with subarachnoid hemorrhage (SAH) due to a ventral dissecting mid-basilar aneurysm that was treated surgically. One week after surgery, the patient experienced sudden deterioration due to a new SAH caused by the development of a new aneurysm of the basilar trunk distinct from the previously clipped aneurysm. CASE DESCRIPTION: A 54-year-old woman with acute subarachnoid hemorrhage was found to have a small, broad-based aneurysm arising from the ventral aspect of the mid-basilar artery. This complicated lesion was treated with a microsurgical clipping via a translabyrinthine pre-sigmoidal sub-temporal approach. One week postoperatively, the patient suffered a new SAH and was found to have developed a distinct basilar artery aneurysm. The patient was returned to the Operating Room for microsurgical clipping via the previous craniotomy. After surgery, the patient made a slow, but steady, recovery. She underwent repeated angiographic imaging, demonstrating a stable appearance. Two years post surgery, the patient had returned to work and had no obvious neurological deficit, with the exception of unilateral iatrogenic hearing loss. CONCLUSION: We describe a rare case of multiple aneurysms originating in relation to a mid-basilar dissection, resulting in multiple episodes of SAH. These are difficult and dangerous lesions that can be treated with open microsurgical reconstruction or possibly via an endovascular approach. The intricate location of the lesions poses a particular challenge to neurosurgeons attempting to directly treat mid-basilar lesions. PMID- 22059123 TI - Nucleus caudalis lesioning: Case report of chronic traumatic headache relief. AB - BACKGROUND: The nucleus caudalis dorsal root entry zone (DREZ) surgery is used to treat intractable central craniofacial pain. This is the first journal publication of DREZ lesioning used for the long-term relief of an intractable chronic traumatic headache. CASE DESCRIPTION: A 40-year-old female experienced new-onset bi-temporal headaches following a traumatic head injury. Despite medical treatment, her pain was severe on over 20 days per month, 3 years after the injury. The patient underwent trigeminal nucleus caudalis DREZ lesioning. Bilateral single-row lesions were made at 1-mm interval between the level of the obex and the C2 dorsal nerve roots, using angled radiofrequency electrodes, brought to 80 degrees C for 15 seconds each, along a path 1 to 1.2 mm posterior to the accessory nerve rootlets. The headache improved, but gradually returned. Five years later, her headaches were severe on over 24 days per month. The DREZ surgery was then repeated. Her headaches improved and the relief has continued for 5 additional years. She has remained functional, with no limitation in instrumental activities of daily living. CONCLUSIONS: The nucleus caudalis DREZ surgery brought long-term relief to a patient suffering from chronic traumatic headache. PMID- 22059124 TI - Sacral laminoplasty and cystic fenestration in the treatment of symptomatic sacral perineural (Tarlov) cysts: Technical case report. AB - BACKGROUND: Perineural cysts of the sacrum, or Tarlov cysts, are cerebrospinal fluid (CSF)-filled sacs that commonly occur at the intersection of the dorsal root ganglion and posterior nerve root in the lumbosacral spine. Although often asymptomatic, these cysts have the potential to produce significant symptoms, including pain, weakness, and/or bowel or bladder incontinence. We present a case in which the sacral roof is removed and reconstructed via plated laminoplasty and describe how this technique could be of potential use in maximizing outcomes. METHODS: We describe technical aspects of a sacral laminoplasty in conjunction with cyst fenestration for a symptomatic sacral perineural cyst in a 50-year-old female with severe sacral pain, lumbosacral radiculopathy, and progressive incontinence. This patient had magnetic resonance imaging (MRI) and computed tomography (CT)-myelographic evidence of a non-filling, 1.7 * 1.4 cm perineural cyst that was causing significant compression of the cauda equina and sacral nerve roots. This surgical technique was also employed in a total of 18 patients for symptomatic tarlov cysts with their radiographic and clinical results followed in a prospective fashion. RESULTS: Intraoperative images, drawings, and video are presented to demonstrate both the technical aspects of this technique and the regional anatomy. Postoperative MRI scan demonstrated complete removal of the Tarlov cyst. The patient's symptoms improved dramatically and she regained normal bladder function. There was no evidence of radiographic recurrence at 12 months. At an average 16 month followup interval 10/18 patients had significant relief with mild or no residual complaints, 3/18 reported relief but had persistent coccydynia around the surgical area, 2/18 had primary relief but developed new low back pain and/or lumbar radiculopathy, 2/18 remained at their preoperative level of symptoms, and 1/18 had relief of their preoperative leg pain but developed new pain and neurological deficits. CONCLUSIONS: Sacral laminoplasty and microscopic cystic fenestration is a feasible approach in the operative treatment of this difficult, and often controversial, spinal pathology. This technique may be used further and studied in an attempt to minimize potential surgical morbidity, including CSF leaks, cyst recurrence, and sacral insufficiency fractures. PMID- 22059125 TI - Post-transplantation primary central nervous system lymphoma: A case report and review of the literature. AB - BACKGROUND: Post-transplantation primary central nervous system lymphoma (PT PCNSL) is a rare neoplasm that can develop within months to years after transplantation, and imaging often reveals multiple lesions with homogeneous or ring enhancement. The clinical and imaging presentation of PT-PCNSL can often be nonspecific and present a diagnostic challenge. CASE DESCRIPTION: A 56-year-old woman presented to a tertiary university emergency room with altered mental status 15 months after undergoing renal transplantation. On brain MRI, she was found to have three rim-enhancing mass lesions, and biopsy revealed PT-PCNSL. CONCLUSION: There has been a steady increase in the number of patients living following organ transplantation in the United States and an increasing likelihood that PT-PCNSL will increasingly be encountered in neurosurgical practice. We present here a case of PT-PCNSL and a brief review of the relevant clinical characteristics, treatment options, and prognosis of PT-PCNSL. PMID- 22059126 TI - The importance of testing deep brain stimulation lead impedances before final lead implantation. AB - BACKGROUND: In the setting of a deep brain stimulation (DBS) lead with defective electrical circuitry, potential patient morbidity and additional surgery may be avoided if impedance testing of the brain lead is performed prior to final lead implantation. In the present report, detection of a short circuit upon lead placement and prior to lead anchoring was detected utilizing recently released DBS hardware and software (Medtronic, Minneapolis, MN). This report suggests that neurosurgeons need to be aware and consider the use of the newly available DBS testing equipment. METHODS: During the first DBS lead placement in a 69-year-old man with advanced idiopathic Parkinson's disease undergoing bilateral subthalamic nucleus DBS over staged procedures, test stimulation and lead impedance testing were accomplished prior to lead anchoring. An external neurostimulator (ENS) was affixed to an updated clinician programmer and connected to the DBS lead with a screening cable specific for the ENS and DBS. RESULTS: Impedance testing demonstrated a short circuit involving the 1 and 3 lead-electrode bipolar combination in a visually intact lead. The lead was replaced, repeat impedance testing and test stimulation were completed and the intact lead was secured. Subsequent DBS surgeries were completed uneventfully. The lead abnormality was verified by the manufacturer. CONCLUSIONS: This case highlights a new method to test DBS lead circuitry at the time of placement. The method may also be employed to directly test lead integrity when localizing a DBS system short or open circuit of unclear etiology. Our case suggests that the method is valuable and should be utilized. PMID- 22059127 TI - Post-surgical spine syndrome. PMID- 22059128 TI - A role for motor and somatosensory evoked potentials during anterior cervical discectomy and fusion for patients without myelopathy: Analysis of 57 consecutive cases. AB - BACKGROUND: Although the usage of combined motor and sensory intraoperative monitoring has been shown to improve the surgical outcome of patients with cervical myelopathy, the role of transcranial electric motor evoked potentials (tceMEP) used in conjunction with somatosensory evoked potentials (SSEP) in patients presenting with radiculopathy but without myelopathy has been less clear. METHODS: We retrospectively reviewed all patients (n = 57) with radiculopathy but without myelopathy, undergoing anterior cervical decompression and fusion at a single institution over the past 3 years, who had intraoperative monitoring with both tceMEPs and SSEPs. RESULTS: Fifty-seven (100%) patients presented with radiculopathy, 53 (93.0%) with mechanical neck pain, 35 (61.4%) with motor dysfunction, and 29 (50.9%) with sensory deficits. Intraoperatively, 3 (5.3%) patients experienced decreases in SSEP signal amplitudes and 4 (6.9%) had tceMEP signal changes. There were three instances where a change in neuromonitoring signal required intraoperative alteration of the surgical procedure: these were deemed clinically significant events/true positives. SSEP monitoring showed two false positives and two false negatives, whereas tceMEP monitoring only had one false positive and no false negatives. Thus, tceMEP monitoring exhibited higher sensitivity (33.3% vs. 100%), specificity (95.6% vs. 98.1%), positive predictive value (33.3% vs. 75.0%), negative predictive value (97.7% vs. 100%), and efficiency (91.7% vs. 98.2%) compared to SSEP monitoring alone. CONCLUSIONS: Here, we present a retrospective series of 57 patients where tceMEP/SSEP monitoring likely prevented irreversible neurologic damage. Though further prospective studies are needed, there may be a role for combined tceMEP/SSEP monitoring for patients undergoing anterior cervical decompression without myelopathy. PMID- 22059129 TI - "Real-world" comparison of non-invasive imaging to conventional catheter angiography in the diagnosis of cerebral aneurysms. AB - BACKGROUND: Based on numerous reports citing high sensitivity and specificity of non-invasive imaging [e.g. computed tomography angiography (CTA) or magnetic resonance angiography (MRA)] in the detection of intracranial aneurysms, it has become increasingly difficult to justify the role of conventional angiography [digital subtraction angiography (DSA)] for diagnostic purposes. The current literature, however, largely fails to demonstrate the practical application of these technologies within the context of a "real-world" neurosurgical practice. We sought to determine the proportion of patients for whom the additional information gleaned from 3D rotational DSA (3DRA) led to a change in treatment. METHODS: We analyzed the medical records of the last 361 consecutive patients referred to a neurosurgeon at our institution for evaluation of "possible intracranial aneurysm" or subarachnoid hemorrhage (SAH). Only those who underwent non-invasive vascular imaging within 3 months prior to DSA were included in the study. For asymptomatic patients without a history of SAH, aneurysms less than 5 mm were followed conservatively. Treatment was advocated for patients with unruptured, non-cavernous aneurysms measuring 5 mm or larger and for any non cavernous aneurysm in the setting of acute SAH. RESULTS: For those who underwent CTA or MRA, the treatment plan was changed in 17/90 (18.9%) and 22/73 (30.1%), respectively, based on subsequent information gleaned from DSA. Several reasons exist for the change in the treatment plan, including size and location discrepancies (e.g. cavernous versus supraclinoid), or detection of a benign vascular variant rather than a true aneurysm. CONCLUSIONS: In a "real-world" analysis of intracranial aneurysms, DSA continues to play an important role in determining the optimal management strategy. PMID- 22059130 TI - Thrombosed giant aneurysm of the distal anterior cerebral artery treated with aneurysm resection and proximal pericallosal artery-callosomarginal artery end-to end anastomosis: Case report and review of the literature. AB - BACKGROUND: Giant distal anterior cerebral artery (DACA) aneurysms are extremely rare, with only 32 cases reported in the literature. Most giant DACA aneurysms have features that make standard neck clipping difficult, and bypass surgery is sometimes required, although this surgery was performed in only three reported cases. This report presents the fourth case treated with bypass surgery. CASE DESCRIPTION: A 69-year-old female presented with an unruptured thrombosed giant DACA aneurysm. She underwent wrapping operation 7 years before, but radiological imaging revealed enlargement of the aneurysm at the left pericallosal artery (PerA)-callosomarginal artery (CMA) junction. Before operation, three different strategies were considered for bypass surgery in case the neck could not be clipped. Aneurysm resection and left proximal PerA-CMA end-to-end anastomosis were successfully performed under intraoperative digital subtraction angiography (DSA) and motor-evoked potential (MEP) monitoring. CONCLUSION: Most DACA aneurysms are located at the PerA-CMA junction. In some cases, adequate retrograde flow to the distal PerA from the posterior or middle cerebral artery can be expected, making distal PerA reconstruction unnecessary. Moreover, when the distal PerA is cut, proximal PerA-CMA end-to-end anastomosis can be easily performed because of reduced tension in both vessels. We therefore conclude that this strategy should be utilized for treating such patients. We also presented here the effectiveness of intraoperative modalities, such as intraoperative DSA and MEP monitoring, for performing a safe operation. PMID- 22059131 TI - Malignant psammomatous melanotic schwannoma of the spine: A component of Carney complex. AB - BACKGROUND: Psammomatous melanotic schwannomas (PMS) of the spine may be a component of the Carney complex in 50% of cases and is inherited in an autosomal dominant manner. Most PMS are benign and frequently associated with lentiginous pigmentation; cardiac, cutaneous, or breast myxomas; endocrine overactivity; and cutaneous blue nevi. These tumors are characterized by melanin containing cells having ultrastructural characteristics of Schwann cells. CASE DESCRIPTION: Two patients had spinal PMS that were surgically resected with adjacent local radiotherapy, followed by local recurrence and metastasis. The aggressive nature of this tumor is reported. CONCLUSION: Spinal PMS are rarely malignant with local recurrence and distal metastases. Inquiry into the patient's and family members' hereditary background for the Carney complex is important to avoid overlooking potential lethal associated abnormalities. PMID- 22059132 TI - Thoraco-lumbar artery aneurysms associated with a metameric paraspinal lesion presenting with retroperitoneal hemorrhage: Endovascular management. AB - BACKGROUND: Retroperitoneal hemorrhage is a life-threatening condition. This is the first reported case of rupture of one of multiple thoraco-lumbar artery aneurysms associated with a metameric paraspinal vascular lesion. CASE DESCRIPTION: A 77-year-old female patient presented to the emergency room with a new onset of left-sided low back pain shooting down the leg associated with weakness, numbness, and inability to walk. On physical examination, there was a notable left paraspinal swelling with a harsh bruit audible in the same area, left flank ecchymosis and a positive straight leg raising test. A computed tomography (CT) scan showed a large retroperitoneal hematoma. Digital subtraction angiography showed a large left paraspinal high-flow arteriovenous lesion, with large arterial aneurysms of the left T11, T12, and L1 segmental arteries. The patient was successfully treated with endovascular aneurysm embolization using coils and Onyx-34. Six months following the procedure, the patient had fully recovered, and a follow-up angiogram showed no residual or recurrent aneurysms. CONCLUSION: Thoraco-lumbar artery aneurysms have never previously been described in association with a metameric paraspinal vascular malformation. We report a case of retroperitoneal hemorrhage due to rupture of one of several high-flow artery aneurysms of a paraspinal arteriovenous malformation (AVM). The diagnosis was made on CTA, MRI, and angiography, and the lesion was successfully treated by transarterial embolization. PMID- 22059133 TI - Spontaneous C1 anterior arch fracture as a postoperative complication of foramen magnum decompression for Chiari malformation type 1. AB - BACKGROUND: C1 fracture accounts for 2% of all spinal column injuries and 10% of cervical spine fractures, and is most frequently caused by motor vehicle accidents and falls. We present a rare case of C1 anterior arch fracture following standard foramen magnum decompression for Chiari malformation type 1. CASE DESCRIPTION: A 63-year-old man underwent standard foramen magnum decompression (suboccipital craniectomy and C1 laminectomy) under a diagnosis of Chiari malformation type 1 with syringomyelia in June 2009. The postoperative course was uneventful until the patient noticed progressive posterior cervical pain 5 months after the operation. Computed tomography of the upper cervical spine obtained 7 months after the operation revealed left C1 anterior arch fracture. The patient was referred to our hospital at the end of January 2010 and C1-C2 posterior fusion with C1 lateral mass screws and C2 laminar screws was carried out in March 2010. Complete pain relief was achieved immediately after the second operation, and the patient resumed his daily activities. CONCLUSION: Anterior atlas fracture following foramen magnum decompression for Chiari malformation type 1 is very rare, but C1 laminectomy carries the risk of anterior arch fracture. Neurosurgeons should recognize that fracture of the atlas, which commonly results from an axial loading force, can occur in the postoperative period in patients with Chiari malformation. PMID- 22059134 TI - Impact of total disc arthroplasty on the surgical management of lumbar degenerative disc disease: Analysis of the Nationwide Inpatient Sample from 2000 to 2008. AB - BACKGROUND: Spinal fusion is the most rapidly increasing type of lumbar spine surgery for various lumbar degenerative pathologies. The surgical treatment of lumbar spine degenerative disc disease may involve decompression, stabilization, or arthroplasty procedures. Lumbar disc athroplasty is a recent technological advance in the field of lumbar surgery. This study seeks to determine the clinical impact of anterior lumbar disc replacement on the surgical treatment of lumbar spine degenerative pathology. This is a retrospective assessment of the Nationwide Inpatient Sample (NIS). METHODS: The NIS was searched for ICD-9 codes for lumbar and lumbosacral fusion (81.06), anterior lumbar interbody fusion (81.07), and posterolateral lumbar fusion (81.08), as well as for procedure codes for revision fusion surgery in the lumbar and lumbosacral spine (81.36, 81.37, and 81.38). To assess lumbar arthroplasty, procedure codes for the insertion or replacement of lumbar artificial discs (84.60, 84.65, and 84.68) were queried. Results were assayed from 2000 through 2008, the last year with available data. Analysis was done using the lme4 package in the R programming language for statistical computing. RESULTS: A total of nearly 300,000 lumbar spine fusion procedures were reported in the NIS database from 2000 to 2008; assuming a representative cross-section of the US health care market, this models approximately 1.5 million procedures performed over this time period. In 2005, the first year of its widespread use, there were 911 lumbar arthroplasty procedures performed, representing 3% of posterolateral fusions performed in this year. Since introduction, the number of lumbar spine arthroplasty procedures has consistently declined, to 653 total procedures recorded in the NIS in 2008. From 2005 to 2008, lumbar arthroplasties comprised approximately 2% of lumbar posterolateral fusions. Arthroplasty patients were younger than posterior lumbar fusion patients (42.8 +/- 11.5 vs. 55.9 +/- 15.1 years, P < 0.0000001). The distribution of arthroplasty procedures was even between academic and private urban facilities (48.5% and 48.9%, respectively). While rates of posterolateral lumbar spine fusion steadily grew during the period (OR 1.06, 95% CI: 1.05-1.06, P < 0.0000001), rates of revision surgery and anterior spinal fusion remained static. CONCLUSIONS: The impact of lumbar arthroplasty procedures has been minimal. Measured as a percentage of more common lumbar posterior arthrodesis procedures, lumbar arthroplasty comprises only approximately 2% of lumbar spine surgeries performed in the United States. Over the first 4 years following the Food and Drug Administration (FDA) approval, the frequency of lumbar disc arthroplasty has decreased while the number of all lumbar spinal fusions has increased. PMID- 22059135 TI - Anterior clinoidectomy: Description of an alternative hybrid method and a review of the current techniques with an emphasis on complication avoidance. AB - BACKGROUND: Anterior clinoidectomy is a difficult but important part of surgery for a variety of parasellar, proximal carotid and central skull base pathologies. First developed intradurally nearly 60 years ago, the promotion of an extradural technique decades later offered an approach with a different set of difficulties, risks and benefits. Many recent studies have demonstrated that there is no consensus about the "correct side" of the dura from which to remove the anterior clinoid process in a number of pathologies. Here, we review and compare the current techniques for intra- and extradural clinoidectomy and describe a hybrid alternative technique. METHODS: We used a hybrid method to potentially engage the advantages of the intradural and extradural techniques. The hybrid method starts with an extradural sphenoid wing osteotomy to the level of the superior orbital fissure (SOF). The dura is then incised parallel to the sphenoid wing lateral to the SOF, and the need for further bony removal, including clinoidectomy, is assessed after gentle elevation of the frontal lobe and release of cerebrospinal fluid through opening the optico-carotid cisterns and inspection of the pathology in relation to the clinoid. Sylvian fissure may be dissected to relieve retraction on the frontal lobe. RESULTS: The hybrid method allows an early identification of the optic nerve and its protection during clinoidectomy. The operator leaves the dura medial to the SOF intact and the clionoidectomy proceeds in an extradural fashion while intradural inspection periodically is performed to assess the extent of necessary extradural bony removal. CONCLUSION: The hybrid method theoretically can be used as a versatile method under some circumstances. Cutting the dura along the sphenoid wing will prevent the dural layers from obscuring the clinoid and offers intradural visualization to monitor the lesion and potentially tailor bony removal. PMID- 22059136 TI - Relocation of ventricular catheter trough ventriculostomy due to congenital unilateral hydrocephalus: Nine year follow-up. AB - BACKGROUND: Congenital unilateral hydrocephalus is an uncommon entity occurring almost exclusively in children. Atresia, stenosis, membranous occlusion and even functional obstruction of the foramen of Monro have been described to be the main cause of this type of hydrocephalus. There are two options available in the surgical management of unilateral hydrocephalus: one is the placement of shunt CSF diversion from the dilated ventricle and the other is fenestration of the occluded foramen of Monro or septum pellucidum by endoscopy or by stereotactic method. Migration of the ventriculoperitoneal (VP) shunt in or out of ventricles is not so uncommon, but the relocation of the ventricular tip of a catheter from the ventricle into the quadrigeminal cisterns and superior vermis in association with ventriculostomy is extremely rare. Spontaneous ventriculostomy is a rare event and results from spontaneous rupture of a ventricle into the subarachnoid space. CASE DESCRIPTION: A 51/2-month-old baby with a right-sided congenital unilateral hydrocephalus underwent a VP shunt andhad experienced an uneventful outcome. Four years later on an MR imaging examination, the tip of the ventricular catheter passing through the medial wall of the ventricle and the quadrigeminal cistern was found to be situated in the superior vermis. During the follow-up period, there were no neurological difficulties. The cognitive and motor skill development corresponded well with the child's age. It transpired that the hydrocephalic ventricle reduced its size dramatically to normal. CONCLUSION: We have described the extremely rare site of the relocation of the ventricular catheter after the treatment of the congenital unilateral hydrocephalus by VP shunting. Spontaneous ventriculostomy as a rare phenomenon may be the explanation of the relocation of the ventricular catheter. PMID- 22059137 TI - Use of preoperative magnetic resonance imaging T1 and T2 sequences to determine intraoperative meningioma consistency. AB - BACKGROUND: Meningioma firmness is a critical factor that influences ease of resection and risk, notably when operating on tumors intimate with neurovascular structures such as the mesial sphenoid wing. This study develops a predictive tool using preoperative magnetic resonance imaging (MRI) characteristics to determine meningioma consistency. METHODS: 101 patients with intracranial meningioma (50 soft/51 firm) were included. MRI characteristics of 38 tumors (19 soft/19 firm) were retrospectively reviewed to identify preoperative imaging features that were then correlated with intraoperative description of the tumor as either "soft and/or suckable" or "firm and/or fibrous". Criteria were developed to predict consistency and then blindly applied to the remaining 63 meningiomas (31 soft/32 firm). RESULTS: The overall sensitivities for detecting soft and firm consistency were 90% and 56%, respectively (95% CI = 73-97% and 38 73%; P < 0.001). Compared to gray matter, meningiomas that were T2 hypointense were almost always firm. Soft meningiomas were hyperintense on T2 and hypointense on T1. Soft meningiomas were slightly larger and less likely to be associated with edema. There was a slight preponderance of firm meningiomas in the infratentorial compartment. Grade of meningioma was not predictive. Contrast enhancement, diffusion restriction, changes in overlying bone, intratumoral cysts, and angiographic features were not predictable. CONCLUSIONS: This tool using T1 and T2 series predicts meningioma consistency. Such knowledge should assist the surgeon in preoperative planning and counseling. PMID- 22059138 TI - A review of skin incisions and scalp flaps for the retromastoid approach and description of an alternative technique. AB - BACKGROUND: The retromastoid approach has been effective in exposing the cerebellopontine angle for resection of a variety of lesions, including vestibular schwannomas and decompression of cranial nerves. The following incisions and their variations have been most commonly used for the retromastoid approach: linear (and its variations, such as "lazy S-shaped") and "C-shaped" incision. METHODS: Herein, we describe a curvilinear incision and compare its advantages and disadvantages with the other previously described incisions based on the senior author's experience with 120 retromastoid operations. RESULTS: The senior author has used the curvilinear incision for the last 70 of 120 patients who underwent retromastoid operations. Of these, one patient encountered postoperative cerebrospinal fluid (CSF) leakage through the incision, requiring a repeat operative wound revision, and one patient suffered from a soft asymptomatic pseudomeningocele. Among the initial 50 patients who underwent a linear incision, one patient suffered from a CSF leakage managed with local wound care and another patient required a repeat operation for a tense pseudomeningocele. No wound breakdown or infection was encountered in either group. CONCLUSIONS: The curvilinear incision is simple and efficient and may provide a shorter working distance and protect the suboccipital muscles and associated neurovascular bundle. PMID- 22059139 TI - Ocular melanoma: Keep your eyes open for late brain metastases. AB - BACKGROUND: The most frequent intraocular malignant tumor is choroidal melanoma (CM). Although brain metastasis is a common feature of other types of cancers, metastasis of CM to the brain is a rare entity. CASE DESCRIPTION: The authors report a case of a 28-year-old woman presenting with a single brain metastasis, 10 years after the treatment of a CM. She underwent a total en-bloc resection of the lesion, and the diagnosis was confirmed histopathologically. The patient concomitantly received whole-brain irradiation therapy combined with chemotherapy, with a survival period of 24 months. CONCLUSION: The present case report draws attention to the necessity of a close and lifelong follow-up of patients treated for this malignancy. The international literature is also reviewed. PMID- 22059140 TI - Ectopic pineal chordoma. AB - BACKGROUND: Chordomas are rare tumors that arise from the remnants of embryonic notochord anywhere along the neuroaxis. Even though they may occur in an extraosseous intradural location, the most common sites include the sacrococcygeal and clivus regions. The authors report a unique presentation encompassing the pineal region with metastasis to the peritoneum after a ventriculoperitoneal (VP) shunt procedure and review the current knowledge about their pathophysiology and management. The presentation and clinical history endorse the idea that intradural extraosseous chordomas may be distinct from ecchordosis physaliphora and probably do not derive from it. CASE DESCRIPTION: An 18-year-old male with previous history of VP shunt presented to the emergency room with pain and abdominal distension. Computed tomography (CT) scans revealed a mass in the pineal region and in the abdominal cavity. Histopathologic exams showed chordoma in both abdominal and cranial samples. The patient died due to systemic complications. CONCLUSION: The authors hypothesized that notochord remnants may subsist within the brain and occasionally may generate a neoplastic lesion. PMID- 22059142 TI - Rare case of intracranial Salmonella enteritidis abscess following glioblastoma resection: Case report and review of the literature. AB - BACKGROUND: Worldwide, Salmonella enteritidis (SE) is becoming a common cause of gastrointestinal infections by contaminated food products, mainly eggs. Extra intestinal manifestations such as brain abscess are more commonly associated with Salmonella typhimurium and are rare in adults. We report the clinical features, treatment outcomes and risk factors predisposing our patient to Salmonella enteritidis brain abscess and discuss relevant literature. CASE DESCRIPTION: A 57 year-old-man developed SE subdural empyema, abscess and possible ventriculitis following reoperation for progression of a right temporal glioblastoma. He initially presented with rapidly worsening headaches over a few days, with a wound discharge and associated meningeal signs. An emergent wound washout revealed pus in the epidural, subdural space and resection cavity. An external ventricular drain (EVD) was placed and cultures revealed gram negative rods. Timely intervention, EVD, and antibiotics resulted in complete resolution. Nine cases of Salmonella abscess associated with primary brain tumor have been reported in literature, most frequently caused by SE in association with glioblastoma multiforme (GBM). We describe our management and outcome in addition to discussing neurosurgical literature on the reported cases. CONCLUSIONS: Re operative tumor surgery has a higher incidence of post-operative infections, with Gram positive cocci being the most common pathogens. Predisposing factors reported for intracranial salmonellosis include compromised immunity, diabetes, HIV, and recent travel. Chronic corticosteroid use, multiple regimens of chemotherapy, and regions of tumor necrosis likely potentiate this rare infection in GBM patients. PMID- 22059143 TI - Decompressive craniectomy bone flap hinged on the temporalis muscle: A new inexpensive use for an old neurosurgical technique. AB - BACKGROUND: The neurosurgical procedure of hinge decompressive craniectomy (hDC), or hinge craniotomy (HC), as described from units in the advanced countries makes use of metallic implants, usually titanium plates and screws, which may not be economically viable in resource-limited practice settings. METHODS: We describe our surgical techniques for performing this same procedure of hDC in a developing country using the patient's own temporalis muscle instead of any other potentially costly implants. RESULTS: The technique as described appears to be successful in achieving intracranial decompression in cases of traumatic brain swelling in which it has been used. Clinical and radiological illustrations of the feasibility, and practical utility, of the procedures in four clinical scenarios of traumatic brain injury are presented. Like all other techniques of HC, this new surgical technique of hDC temporalis saves the survivors the added imperative of future cranioplasty of the usual postcraniectomy skull defect. Unlike the others, the procedure eliminates the added cost of the metallic implants needed to perform the former techniques. CONCLUSIONS: The procedure of hDC temporalis appears to be a viable option for performing the surgical procedure of HC and has added cost-cutting economic benefits for resource-limited practice settings. PMID- 22059141 TI - Stuck at the bench: Potential natural neuroprotective compounds for concussion. AB - BACKGROUND: While numerous laboratory studies have searched for neuroprotective treatment approaches to traumatic brain injury, no therapies have successfully translated from the bench to the bedside. Concussion is a unique form of brain injury, in that the current mainstay of treatment focuses on both physical and cognitive rest. Treatments for concussion are lacking. The concept of neuro prophylactic compounds or supplements is also an intriguing one, especially as we are learning more about the relationship of numerous sub-concussive blows and/or repetitive concussive impacts and the development of chronic neurodegenerative disease. The use of dietary supplements and herbal remedies has become more common place. METHODS: A literature search was conducted with the objective of identifying and reviewing the pre-clinical and clinical studies investigating the neuroprotective properties of a few of the more widely known compounds and supplements. RESULTS: There are an abundance of pre-clinical studies demonstrating the neuroprotective properties of a variety of these compounds and we review some of those here. While there are an increasing number of well designed studies investigating the therapeutic potential of these nutraceutical preparations, the clinical evidence is still fairly thin. CONCLUSION: There are encouraging results from laboratory studies demonstrating the multi-mechanistic neuroprotective properties of many naturally occurring compounds. Similarly, there are some intriguing clinical observational studies that potentially suggest both acute and chronic neuroprotective effects. Thus, there is a need for future trials exploring the potential therapeutic benefits of these compounds in the treatment of traumatic brain injury, particularly concussion. PMID- 22059144 TI - Choroid plexus papilloma originating from the cerebrum parenchyma. AB - BACKGROUND: Choroid plexus papilloma (CPP) can develop at a primary intraparenchymal location completely unrelated to the ventricular system. Here, we present a case of CPP that was difficult to diagnose preoperatively. CASE DESCRIPTION: Preoperative imaging and operative findings showed that the tumor originated entirely within the cerebrum parenchyma, with no connections between the tumor and the ventricular system. Histopathological examination of the tumor revealed a papillary structure with a single layer of well-differentiated columnar epithelium in the lesion. Furthermore, part of this lesion had infiltrated the cerebral parenchyma. Therefore, the tumor was diagnosed as CPP, and the diagnosis was confirmed by immunohistological examination. CONCLUSIONS: CPP originating as intraparenchymal growths are extremely rare. Origins of extraventricular CCP are discussed in the context of the literature. PMID- 22059145 TI - Autofocus methods of whole slide imaging systems and the introduction of a second generation independent dual sensor scanning method. AB - Accurate focusing is a critical challenge of whole slide imaging, primarily due to inherent tissue topography variability. Traditional line scanning and tile based scanning systems are limited in their ability to acquire a high degree of focus points while still maintaining high throughput. This review examines limitations with first-generation whole slide scanning systems and explores a novel approach that employs continuous autofocus, referred to as independent dual sensor scanning. This "second-generation" concept decouples image acquisition from focusing, allowing for rapid scanning while maintaining continuous accurate focus. The technical concepts, merits, and limitations of this method are explained and compared to that of a traditional whole slide scanning system. PMID- 22059146 TI - High-definition hematoxylin and eosin staining in a transition to digital pathology. AB - INTRODUCTION: A lot of attention has been generated in recent years by digital pathology and telepathology. Multiple reasons for and barriers to effective adoption are discussed in the current literature. Digital slides are the most promising medium at this time. The goal of our study was to evaluate whether the change in the methodology, particularly utilizing the so-called high-definition hematoxylin and eosin (H and E) slides, enhanced the quality of the final digital slide, and whether pathologists who tested the results perceived this as a difference in quality. METHODS: THE STUDY WAS A BLINDED COMPARISON OF DIGITAL SLIDES PREPARED USING TWO METHODS: standard H&E batch staining and automated individual "high definition" HD HE staining. Four pathologists have compared 80 cases stained with each method. RESULTS: The results discussed in this study show potential promise that the utilization of protocol(s) adapted for tissue and for imaging might be preferable for digital pathology in at least some of the pathology subspecialties. In particular, the protocol evaluated here was capable of turning out digital slides that had more contrast and detail, and therefore were perceived to provide enhanced diagnostically significant information for the pathologist. PMID- 22059147 TI - Evaluation and optimization for liquid-based preparation cytology in whole slide imaging. AB - BACKGROUND: Cytology poses different obstacles in whole slide imaging compared to surgical pathology slides. A single focal plane suffices for most of the latter, but cytology slides are thicker, potentially requiring multiple focal planes for adequate diagnostic information. Multiple focal planes adversely impact scanning time per slide, evaluation times, and file sizes. In this pilot study, we evaluated and compared the multilayer stack method to the extended focus algorithm as an alternative which collapses multiple focal planes into a single image, retaining only focused areas from each plane. MATERIALS AND METHODS: 10 SurePath((r)) cervical cytology slides were scanned at three thickness settings: 18, 24, and 30 MUm. Three scanners were used: (1) Hamamatsu Nanozoomer 2.0-HT, (2) 3DHISTECH Mirax scan, and (3) Bioimagene iScan Coreo Au. The Nanozoomer and iScan utilized multilayer stacking, while the Mirax files were composited by extended focus. Scan times and file sizes were recorded, and image quality compared. RESULTS: The Nanozoomer stacks averaged 1.58 gb and around 25 min for each slide, while the iScan stacks ranged from 6.23 to 9.3 gb and took 34-50 min to scan. The Mirax images averaged 210 mb and took 13-20 min to scan. Multilayer stack image quality from both Nanozoomer and iScan was fairly comparable. The iScan revealed significant mechanical issues that did not correspond to user settings. The Mirax images showed worrisome loss of crisp focus detail, worsening with increasing focal planes and impacting assessment of nuclear contours and chromatin detail. CONCLUSIONS: The optimal number of focal planes remains unknown for cytology. Multilayer stacks require excessive scanning time, network bandwidth, and file storage. Extended focus was evaluated as an alternative, but significant image quality issues were revealed. Further large-scale studies are needed to assess their clinical impact. PMID- 22059148 TI - Imaging findings in Chiari I malformation with syringomyelia in a case of charcot shoulder. AB - Neuropathic arthropathy of the shoulder is reported in only 5% of cases. Here, we report a rare case of neuropathic arthropathy of the shoulder, secondary to Chiari malformation Type I with associated syringomyelia, that remained undetected for four years. A 38-year-old female presented to our Department with a swelling over the right shoulder that had persisted for four years. X-ray of the joint showed destruction of the head of the right humerus, with typical blunt amputated appearance of the bone and increased joint space. Magnetic resonance imaging showed destruction and lateral dislocation of the head of the humerus. Large amount of fluid collection was seen in and around the right shoulder joint. Neuropathic osteoarthropathy can be defined as bone and joint changes that occurs secondary to loss of sensation. In our case, neuropathic shoulder joint was secondary to syringomyelia associated with Chiari I malformation. PMID- 22059149 TI - Congenital agenesis of the left lung: a rare case. AB - Pulmonary agenesis is a rare congenital anomaly, the etiology of which is not clearly known. Other systemic comorbidities such as cardiovascular, gastrointestinal, musculoskeletal, and urogenital system anomalies can be observed in more than half of the patients. It is usually diagnosed during childhood. Diagnosis in adulthood is very rare. We present a case of pulmonary agenesis diagnosed in an adult. PMID- 22059150 TI - Breast MR Imaging: What the Radiologist Needs to Know. AB - Magnetic resonance imaging (MRI) of the breast is being performed more frequently to improve primary and recurrent tumor detection, characterization, and response to therapy. Sensitivity of this test approaches 90% and the specificity ranges from 37% to 100%. We present a concise tutorial for the general radiologist with a pictorial review of common lesions identified with breast MRI. PMID- 22059151 TI - Imaging acute appendicitis: state of the art. AB - The goal of this review is to present the state of the art in imaging tests for the diagnosis of acute appendicitis. Relevant publications regarding performance and advantages/disadvantages of imaging modalities for the diagnosis of appendicitis in different clinical situations were reviewed. Articles were extracted from a computerized database (MEDLINE) with the following activated limits: Humans, English, core clinical journals, and published in the last five years. Reference lists of relevant studies were checked manually to identify additional, related articles. Ultrasound (US) examination should be the first imaging test performed, particularly among the pediatric and young adult populations, who represent the main targets for appendicitis, as well as in pregnant patients. A positive US examination for appendicitis or an alternative diagnosis of possible gastrointestinal or urological origin, or a negative US, either showing a normal appendix or presenting low clinical suspicion of appendicitis, should lead to a final diagnosis. A negative or indeterminate examination with a strong clinical suspicion of appendicitis should be followed by a computed tomography (CT) scan or alternatively, a magnetic resonanace imaging (MRI) scan in a pregnant patient. A second US examination in a patient with persistent symptoms, especially if the first one was performed by a less experienced imaging professional, is a valid alternative to a CT. PMID- 22059152 TI - An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. AB - Glioblastoma (GBM) is the most common malignant primary brain tumor of adults and one of the most lethal of all cancers. Epidermal growth factor receptor (EGFR) mutations (EGFRvIII) and phosphoinositide 3-kinase (PI3K) hyperactivation are common in GBM, promoting tumor growth and survival, including through sterol regulatory element-binding protein 1 (SREBP-1)-dependent lipogenesis. The role of cholesterol metabolism in GBM pathogenesis, its association with EGFR/PI3K signaling, and its potential therapeutic targetability are unknown. In our investigation, studies of GBM cell lines, xenograft models, and GBM clinical samples, including those from patients treated with the EGFR tyrosine kinase inhibitor lapatinib, uncovered an EGFRvIII-activated, PI3K/SREBP-1-dependent tumor survival pathway through the low-density lipoprotein receptor (LDLR). Targeting LDLR with the liver X receptor (LXR) agonist GW3965 caused inducible degrader of LDLR (IDOL)-mediated LDLR degradation and increased expression of the ABCA1 cholesterol efflux transporter, potently promoting tumor cell death in an in vivo GBM model. These results show that EGFRvIII can promote tumor survival through PI3K/SREBP-1-dependent upregulation of LDLR and suggest a role for LXR agonists in the treatment of GBM patients. PMID- 22059153 TI - Extracellular/circulating microRNAs and their potential role in cardiovascular disease. AB - microRNAs (miRs, miRNAs) are small non-coding RNAs that regulate hundreds of gene expression. Numerous studies have demonstrated that miRNAs are not only found intracellularly, but also detectable outside cells, including various body fluids (i.e. serum, plasma, saliva, urine, breast milk, and tears). Interestingly, ~90% of extracellular miRNAs are packaged with proteins (i.e. Ago2, HDL, and other RNA binding proteins) and ~10% are wrapped in small membranous particles (i.e. exosomes, microvesicles, and apoptotic bodies). It is believed that these extracellular miRNAs mediate cell-to-cell communication. Recent studies further indicated that the level and composition of these extracellular/circulating miRNAs correlated well with disease or injurious conditions. Uncovering the potential role of extracellular miRNAs in the heart is just emerging. This review will highlight recent exciting findings in the regulation of miRNA biogenesis and secretion, their functional roles in paracrine signaling, and the potential as non-invasive biomarkers for cardiovascular disease. PMID- 22059154 TI - Primary pancreatic lymphoma: a rare cause of massive upper gastrointestinal hemorrhage. PMID- 22059156 TI - Canadian patients with chronic hepatitis B cannot access appropriate drug treatments: a call for change. PMID- 22059157 TI - Helicobacter pylori treatment in the hospital setting: a potential model for developing quality improvement initiatives to prevent missed test results. PMID- 22059158 TI - How well is Helicobacter pylori treated in usual practice? AB - BACKGROUND: Helicobacter pylori is a WHO class I carcinogen also associated with nonmalignant gastrointestinal diseases. Effective treatment exists, and all persons infected with H pylori should receive treatment. However, data regarding the rates of treatment prescription in clinical practice are lacking. OBJECTIVE: To determine the rates of H pylori treatment in usual practice. METHODS: Patients with histological evidence of H pylori infection between January 1, 2007, and December 31, 2007, at Sunnybrook Health Sciences Centre (Toronto, Ontario) were identified. Charts were reviewed to determine the rates of H pylori treatment and confirmation of eradication, when indicated. Questionnaires were subsequently sent to endoscopists of patients identified as not having received treatment to determine the reasons for lack of treatment. RESULTS: A total of 102 patients were H pylori positive and were appropriate candidates for treatment, of whom 58 (57%) were male and 78 (76%) were outpatients, with 92 (90%) receiving eradication therapy. When indicated, 15 of 22 (68%) patients received confirmation of eradication, 13 of 18 (72%) patients underwent repeat endoscopy and 86% received complete therapy. Outpatients were more likely to receive eradication therapy (OR 10.3 [95% CI 2.6 to 40.4]; P=0.001) and complete therapy (OR 13.2 [95% CI 3.8 to 45.7]; P=0.0001) compared with inpatients. Having a follow-up appointment resulted in higher treatment rates (OR 12.0 [95% CI 3.0 to 47.5]; P=0.001). CONCLUSION: During the time period studied, adequate rates of H pylori treatment were achieved in outpatients and patients who had formal follow up at Sunnybrook Health Sciences Centre. However, some aspects of care remain suboptimal including treatment of inpatients and care following treatment. Additional studies are required to identify strategies to improve the care of patients infected with H pylori. PMID- 22059159 TI - Development and implementation of a comprehensive quality assurance program at a community endoscopy facility. AB - Quality assurance (QA) is a process that includes the systematic evaluation of a service, institution of improvements and ongoing evaluation to ensure that effective changes were made. QA is a fundamental component of any organized colorectal cancer screening program. However, it should play an equally important role in opportunistic screening. Establishing the processes and procedures for a comprehensive QA program can be a daunting proposition for an endoscopy unit. The present article describes the steps taken to establish a QA program at the Forzani & MacPhail Colon Cancer Screening Centre (Calgary, Alberta) - a colorectal cancer screening centre and nonhospital endoscopy unit that is dedicated to providing colorectal cancer screening-related colonoscopies. Lessons drawn from the authors' experience may help others develop their own initiatives. The Global Rating Scale, a quality assessment and improvement tool developed for the gastrointestinal endoscopy services of the United Kingdom's National Health Service, was used as the framework to develop the QA program. QA activities include monitoring the patient experience through surveys, creating endoscopist report cards on colonoscopy performance, tracking and evaluating adverse events and monitoring wait times. PMID- 22059160 TI - Retrospective analysis of radiation exposure during endoscopic retrograde cholagiopancreatography: critical determinants. AB - BACKGROUND: Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) has a logarithmic relationship with radiation exposure, and carries a known risk of radiation exposure to patients and staff. Factors associated with prolonged fluoroscopy duration have not been well delineated. OBJECTIVES: To determine the specific patient, physician and procedural factors that affect fluoroscopy duration. METHODS: A retrospective analysis of 1071 ERCPs performed at two tertiary care referral hospitals over an 18-month period was conducted. Patient, physician and procedural variables were recorded at the time of the procedure. RESULTS: The mean duration of 969 fluoroscopy procedures was 4.66 min (95% CI 4.38 to 4.93). Multivariable analysis showed that the specific patient factors associated with prolonged fluoroscopy duration included age and diagnosis (both P<0.0001). The endoscopist was found to play an important role in the duration of fluoroscopy (ie, all endoscopists studied had a mean fluoroscopy duration significantly different from the reference endoscopist). In addition, the following procedural variables were found to be significant: number of procedures, basket use, biopsies, papillotomy (all P<0.0001) and use of a tritome (P=0.004). Mean fluoroscopy duration (in minutes) with 95% CIs for different diagnoses were as follows: common bile duct stones (n=443) 5.12 (3.05 to 4.07); benign biliary strictures (n=135) 3.94 (3.26 to 4.63); malignant biliary strictures (n=124) 5.82 (4.80 to 6.85); chronic pancreatitis (n=49) 4.53 (3.44 to 5.63); bile leak (n=26) 3.67 (2.23 to 5.09); and ampullary mass (n=11) 3.88 (1.28 to 6.48). When no pathology was found (n=195), the mean fluoroscopy time was 3.56 min (95% CI 3.05 to 4.07). Comparison using t tests determined that the only two diagnoses for which fluoroscopy duration was significantly different from the reference diagnosis of 'no pathology found' were common bile duct stones (P<0.0001) and malignant strictures (P<0.0001). CONCLUSIONS: Factors that significantly affected fluoroscopy duration included age, diagnosis, endoscopist, and the number and nature of procedures performed. Elderly patients with biliary stones or a malignant stricture were likely to require the longest duration of fluoroscopy. These identified variables may help endoscopists predict which procedures are associated with prolonged fluoroscopy duration so that appropriate precautions can be undertaken. PMID- 22059161 TI - Strategic plan of the Canadian Institutes of Health Research Institute of Nutrition, Metabolism, and Diabetes. AB - The present document provides the new and updated strategic plan for the Institute of Nutrition, Metabolism, and Diabetes (INMD) of the Canadian Institutes of Health Research. This plan provides an overarching map for the strategic activities of the INMD during the five years from 2010 to 2014. These strategic priorities will guide the way that the INMD uses its resources over this period of time, and will provide opportunities to build new partnerships and strategic alliances that enhance and leverage the capacity to fund targeted research initiatives. PMID- 22059162 TI - Medical management of inflammatory bowel disease among Canadian gastroenterologists. AB - BACKGROUND: Little is known about physician perceptions of and practices in using infliximab - a biological agent that was approved in Canada for the treatment of Crohn's disease in 2001, and for ulcerative colitis in 2006. OBJECTIVES: To describe Canadian gastroenterologists' use and perceptions of infliximab in the treatment of refractory inflammatory bowel disease (IBD), and to identify factors that may influence a gastroenterologist's decision to initiate infliximab therapy. METHODS: A postal questionnaire was distributed to all practicing clinicians captured in the 2007 membership of the Canadian Association of Gastroenterology. Each physician was contacted up to a maximum of three times. RESULTS: Of 466 questionnaires mailed out, responses were received from 336 (72%), with 292 respondents (63%) returning fully completed surveys. For 80% of respondents, IBD patients comprised less than 30% of their clinical practice. Most prescribed infliximab at an initial dose of 5 mg/kg (97%), prescribed loading doses at 0, 2 and 6 weeks (88%), premedicated with corticosteroids (74%), administered maintenance infusions at eight-week intervals (89%), co-administered immunosuppressive agents (81%) and continued infliximab 'indefinitely' as long as it was effective and well tolerated (76%). Most gastroenterologists (>70%) identified lack of drug insurance coverage and provincial funding criteria as important barriers to prescribing infliximab. CONCLUSIONS: Most Canadian gastroenterologists exhibited similar practice patterns with respect to the use of infliximab for induction and maintenance therapy of IBD. Common barriers to the initiation of infliximab therapy were identified. PMID- 22059164 TI - Hepatitis A vaccination of patients with chronic liver disease admitted to hospital: a University of British Columbia medical resident quality assurance pilot project. PMID- 22059165 TI - Superior mesenteric artery syndrome. PMID- 22059166 TI - A bibliometric analysis of digestive health research in Canada: "fair is foul, and foul is fair". PMID- 22059167 TI - Clinical parameters predicting survival duration after hepatectomy for intrahepatic cholangiocarcinoma. AB - BACKGROUND: Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision. OBJECTIVE: To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration. METHODS: Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration. RESULTS: Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level greater than 37 U/mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, respectively. CONCLUSIONS: The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies. PMID- 22059168 TI - A bibliometric analysis of digestive health research in Canada. AB - Measurement of the impact and influence of medical/scientific journals, and of individual researchers has become more widely practiced in recent decades. This is driven, in part, by the increased availability of data regarding citations of research articles, and by increased competition for research funding. Digestive disease research has been identified as a particularly strong discipline in Canada. The authors collected quantitative data on the impact and influence of Canadian digestive health research. The present study involved an analysis of the research impact (Hirsch factor) and research influence (Influence factor) of 106 digestive health researchers in Canada. Rankings of the top 25 researchers on the basis of the two metrics were dominated by the larger research groups at the University of Toronto (Toronto, Ontario), McMaster University (Hamilton, Ontario), and the Universities of Calgary (Calgary, Alberta) and Alberta (Edmonton, Alberta), but with representation by other research groups at the Universities of Manitoba (Winnipeg, Manitoba), Western Ontario (London, Ontario) and McGill University (Montreal, Quebec). Female and male researchers had similar scores for the two metrics, as did basic scientists versus clinical investigators. Strategic recruitment, particularly of established investigators, can have a major impact on the ranking of research groups. Comparing these metrics over different time frames can provide insights into the vulnerabilities and strengths of research groups. PMID- 22059169 TI - 'Short' double-balloon enteroscope endoscopic retrograde cholangiopancreatography in patients with a surgically altered upper gastrointestinal tract. AB - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) remains a challenge for endoscopists in patients with surgically altered anatomy of the upper gastrointestinal tract. Double-balloon enteroscopes (DBEs) have revolutionized the ability to access the small bowel. The indication for its therapeutic use is expanding to include ERCP for patients who have undergone small bowel reconstruction. Most of the published experiences in DBE-assisted ERCP have used conventional double-balloon enteroscopes that are 200 cm in length, which do not permit use of the standard ERCP accessories. The authors report their experience with DBE-assisted ERCP using a 'short' DBE in patients with surgically altered anatomy. METHODS: A retrospective review of patients with previous small bowel reconstruction who underwent ERCP with a 'short' DBE at the Centre for Therapeutic Endoscopy and Endoscopic Oncology (Toronto, Ontario) between February 2007 and November 2008 was performed. RESULTS: A total of 20 patients (10 men) with a mean age of 57.9 years (range 26 to 85 years) underwent 29 sessions of ERCP with a DBE. Six patients underwent Billroth II gastroenterostomy, seven patients Roux-en-Y hepaticojejunostomy, five patients Roux-en-Y gastrojejunostomy, one patient Roux-en-Y esophagojejunostomy and one patient a Whipple's operation with choledochojejunostomy. Some patients (n=12 [60%]) underwent previous attempts at ERCP in which the papilla of Vater or bilioenteric anastomosis could not be reached with either a duodenoscope or pediatric colonoscope. All procedures were performed with a commercially available DBE (working length 152 cm, distal end diameter 9.4 mm, channel diameter 2.8 mm). The procedures were performed under conscious sedation with intravenous midazolam, fentanyl and diazepam, except in one patient in whom general anesthesia was administered. Either the papilla of Vater or bilioenteric anastomosis was reached in 25 of 29 cases (86.2%) in a mean duration of 20.8 min (range 5 min to 82 min). Bile duct cannulation was successful in 24 of 25 cases in which the papilla or bilioenteric anastomosis was reached. Therapeutic interventions were successful in 15 patients (24 procedures) including sphincterotomy (n=7), stone extraction (n=9), biliary dilation (n=8), stent placement (n=9) and stent removal (n=8). The mean total duration of the procedures was 70.7 min (range 30 min to 117 min). There were no procedure related complications. CONCLUSION: DBEs enable successful diagnostic and therapeutic ERCP in patients with a surgically altered anatomy of the upper gastrointestinal tract. It is a safe, feasible and less invasive therapeutic option in this group of patients. Standard 'long' DBEs have limitations of long working length and the need for modified ERCP accessories. 'Short' DBEs are equally as effective in reaching the target limb as standard 'long' DBEs, and overcomes some limitations of long DBEs to result in high success rates for endoscopic therapy. PMID- 22059170 TI - Usefulness of endoscopic ultrasonography in hepatology. AB - Endoscopic ultrasonography (EUS) is used to evaluate patients with hepatobiliary diseases. The technique is useful for the diagnosis of esogastric varices in selected cases of portal hypertension, and to evaluate the pathogenic role and prognostic value of the collateral circulation in patients with this condition. When coupled with the Doppler technique, EUS can be used to guide injection sclerotherapy and to verify the obliteration of varices (particularly fundal varices) after endoscopic treatment. Hemodynamic changes induced in the collateral circulation by vasoactive drugs can also be measured with Doppler-EUS. Fine-needle aspiration under EUS guidance is useful in the diagnosis of focal liver lesions and perihepatic adenopathy, and in the evaluation of biliary tract diseases. New indications can be developed in the future after adequate experimental validation. PMID- 22059171 TI - Endoscopic treatment of obesity. AB - BACKGROUND: The increasing incidence of obesity and overweight among children and adolescents will be reflected by the imminent increase in the number of obese patients who require more definitive methods of treatment. There is great interest in new, safe, simple, nonsurgical procedures for weight loss. OBJECTIVE: To provide an overview of new endoscopic methods for the treatment of obesity. METHODS: An English-language literature search on endoscopic interventions, endoscopically placed devices and patient safety was performed in the MEDLINE and Cochrane Library databases. RESULTS: The literature search yielded the following weight loss methods: space-occupying devices (widely used), gastric capacity reduction, modifying gastric motor function and malabsorptive procedures. A commercially available intragastric balloon was the most commonly used device for weight loss. In specific subgroups of patients, it improved quality of life, decreased comorbidities and served as a bridge to surgery. More evidence regarding the potential benefits and safety of other commercially available intragastric balloons is needed to clarify whether they are superior to the most commonly used one. Moreover, early experiences with transoral gastroplasty, the duodenal-jejunal bypass sleeve and an adjustable, totally implantable intragastric prosthesis, indicate that they may be viable options for obesity treatment. Other agents, such as botulinum toxin and a device known as the 'butterfly', are currently at the experimental stage. CONCLUSION: New endoscopic methods for weight loss may be valuable in the treatment of obesity; however, more clinical experience and technical improvements are necessary before implementing their widespread use. PMID- 22059177 TI - Telehealth technology: an emerging method of delivering pulmonary rehabilitation to patients with chronic obstructive pulmonary disease. PMID- 22059179 TI - Using Telehealth technology to deliver pulmonary rehabilitation in chronic obstructive pulmonary disease patients. AB - BACKGROUND: Pulmonary rehabilitation (PR) is an effective therapeutic strategy to improve health outcomes in patients with chronic obstructive pulmonary disease (COPD); however, there is insufficient PR capacity to service all COPD patients, thus necessitating creative solutions to increase the availability of PR. OBJECTIVE: To examine the efficacy of PR delivered via Telehealth (Telehealth-PR) compared with PR delivered in person through a standard outpatient hospital-based program (Standard-PR). METHODS: One hundred forty-seven COPD patients participated in an eight-week rural PR program delivered via Telehealth-PR. Data were compared with a parallel group of 262 COPD patients who attended Standard PR. Education sessions were administered two days per week via Telehealth, and patients exercised at their satellite centre under direct supervision. Standard PR patients viewed the same education sessions in person and exercised at the main PR site. The primary outcome measure was change in quality of life as evaluated by the St George's Respiratory Questionnaire (SGRQ). A noninferiority analysis was performed using both intention-to-treat and per-protocol approaches. RESULTS: Both Telehealth-PR and Standard-PR resulted in clinically and statistically significant improvements in SGRQ scores (4.5 +/- 0.8% versus 4.1 +/ 0.6%; P<0.05 versus baseline for both groups), and the improvement in SGRQ was not different between the two programs. Similarly, exercise capacity, as assessed by 12 min walk test, improved equally in both Telehealth-PR and Standard-PR programs (81+/-10 m versus 82 +/- 10 m; P<0.05 versus baseline for both groups). CONCLUSION: Telehealth-PR was an effective tool for increasing COPD PR services, and demonstrated improvements in quality of life and exercise capacity comparable with Standard-PR. PMID- 22059178 TI - Home mechanical ventilation: a Canadian Thoracic Society clinical practice guideline. AB - Increasing numbers of patients are surviving episodes of prolonged mechanical ventilation or benefitting from the recent availability of userfriendly noninvasive ventilators. Although many publications pertaining to specific aspects of home mechanical ventilation (HMV) exist, very few comprehensive guidelines that bring together all of the current literature on patients at risk for or using mechanical ventilatory support are available. The Canadian Thoracic Society HMV Guideline Committee has reviewed the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. The guideline provides a disease-specific review of illnesses including amyotrophic lateral sclerosis, spinal cord injury, muscular dystrophies, myotonic dystrophy, kyphoscoliosis, post-polio syndrome, central hypoventilation syndrome, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease as well as important common themes such as airway clearance and the process of transition to home. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information. PMID- 22059180 TI - Persistent sputum cellularity and neutrophils may predict bronchiectasis. AB - BACKGROUND: Quantitative cell counts in sputum provide an accurate assessment of the type and severity of bronchitis. OBJECTIVE: To examine whether sputum cell counts could identify bronchiectasis in patients with recurrent bronchitis. METHODS: A retrospective survey of a clinical database (January 2004 to January 2005) of quantitative cell counts from sputum selected from expectorate in patients with obstructive airways diseases was used to identify predictors of bronchiectasis using ROC curves. This was prospectively evaluated (February 2005 to April 2008) using high-resolution computed tomography scans of thorax that were independently scored by a radiologist who was blinded to the clinical details. RESULTS: The retrospective survey identified 41 patients with bronchiectasis among 490 patients with airway diseases. Total cell count of 60 * 106/g or greater of the selected sputum with predominant neutrophils on two occasions had a sensitivity of 86.7%, a specificity of 87.5%, and positive and negative predictive values of 93% and 78%, respectively, to identify bronchiectasis. In the prospective study, 10 of 14 (71%) patients who met these criteria were identified to have bronchiectasis. Both total cell count and the percentage of neutrophils correlated with radiographic bronchiectasis severity. CONCLUSIONS: Persistent or recurrent intense sputum cellularity with neutrophilia is suggestive of bronchiectasis. PMID- 22059181 TI - Therapeutic drug monitoring in the treatment of active tuberculosis. AB - BACKGROUND: Therapeutic drug monitoring (TDM) is used to optimize dosing that maximizes therapeutic benefit while minimizing toxicity. In the treatment of active tuberculosis (TB), TDM is not routine, yet low levels of anti-TB drugs can be associated with poorer treatment outcomes. METHODS: In a retrospective case control study, patients with active TB in whom TDM was performed were considered cases and compared with controls who did not undergo TDM, and matched according to year of diagnosis and the results of direct smear microscopy. Medical records were reviewed to abstract demographic, clinical, radiographic and microbiological data including time until smear and culture conversion. RESULTS: In total, 20 patients were identified in whom TDM was performed, of whom 17 (87%) had at least one low drug concentration. Overall, 27 of 45 (60%) initial drug concentrations were low and resulted in an increased drug dosage. Low drug levels were found in 13 of 15 (87%) isoniazid, four of five (80%) rifabutin and eight of 12 (67%) rifampin measurements, but in only two of 13 (15%) pyrazinamide measurements. Within cases only, the 17 patients with low serum drug levels were significantly more likely to have comorbid illnesses, be smear positive, have lower serum albumin levels and had nonsignificantly longer time to culture conversion, compared with the three cases in whom all drug levels were within therapeutic ranges. CONCLUSIONS: TB drug levels were frequently below clinically acceptable levels in patients with active TB, particularly in those with HIV infection or other comorbidities. TDM is potentially useful for the treatment of active TB, but is currently underused. PMID- 22059182 TI - Assessing response to therapy in idiopathic pulmonary arterial hypertension: a consensus survey of Canadian pulmonary hypertension physicians. AB - BACKGROUND: Many treatment options are now available for patients with idiopathic pulmonary arterial hypertension (IPAH). Data regarding the optimal combination of therapies are lacking, as is consensus on how to assess response to therapy and when to change therapeutic regimens. OBJECTIVES: To gather the opinions of Canadian pulmonary hypertension (PH) experts regarding standard practice in the care of IPAH patients after therapy is initiated. METHODS: Canadian PH physicians were surveyed using short questionnaires to assess their opinions and practices in the care of IPAH patients. A Delphi forecasting approach was used to gain consensus among Canadian physicians on the most important clinical parameters to consider when assessing patients after the initiation of therapy. RESULTS: Twenty six of 37 Canadian PH experts who were invited to participate completed the study. All endorsed the use of combination therapy for IPAH patients despite the lack of universal provincial coverage for this approach. By consensus, WHO functional class, 6 min walk distance and hospitalization for right heart failure were the most important clinical parameters. The most highly rated physical examination parameters were jugular venous pressure, peripheral edema, the presence of ascites and body weight. CONCLUSIONS: The overall approach to care of IPAH patients is similar across PH centres in Canada. A limited number of clinical and physical examination parameters were considered to be most important to reassess patients after therapy is initiated. These parameters, along with definition of threshold values, will facilitate the development of standard practice guidelines for IPAH patients in Canada. PMID- 22059183 TI - Management of pulmonary embolism with rheolytic thrombectomy. AB - BACKGROUND: Catheter thrombectomy combining thrombus destruction with local thrombolysis has been used in patients with pulmonary embolism (PE) who are unstable or have significant right heart dysfunction, but have contraindications to systemic thrombolytic therapy. OBJECTIVES: To assess the outcomes of patients who underwent pulmonary embolectomy using a commercially available thrombectomy device. METHODS: A retrospective chart review of patients who underwent pulmonary embolectomy between March 2007 and August 2009 was performed. Patients were classified as having clinical massive or submassive PE, and moderate or severe right ventricular dysfunction. Data collected included pre- and postprocedure shock index (heart rate divided by systolic blood pressure) and mean pulmonary artery pressure. RESULTS: Sixteen patients with a mean (+/- SD) age of 54.4 +/- 15.8 years underwent embolectomy. Five had clinical massive PE (two in cardiogenic shock) and three of 11 submassive cases had severe right ventricular dysfunction. All were deemed to have contraindications to systemic lysis. Both shock index (1.02 +/- 33 preintervention versus 0.71 +/- 0.2 postintervention [P=0.001]) and mean pulmonary artery pressure (34.5 +/- 9.9 mmHg preintervention versus 27.1 +/- 7.1 postintervention [P=0.01]) improved. In the massive PE group, one patient died and two survivors experienced retroperitoneal bleeding and transient renal failure. At follow-up (17.3 +/- 7.8 months), two patients in the massive PE group demonstrated evidence of mild cor pulmonale. CONCLUSION: Rheolytic thrombectomy is an effective strategy in managing massive PE, particularly in patients who have well-defined contraindications to systemic lytic therapy. The effectiveness of rheolytic thrombectomy for submassive PE is not as well defined, but warrants a comparison with systemic lytic therapy. PMID- 22059184 TI - Acute respiratory distress following intravenous injection of an oil-steroid solution. AB - A case of acute respiratory distress and hypoxemia following accidental intravenous injection of an oil-steroid solution in a body builder is presented. Chest roentography at the time of presentation showed diffuse bilateral opacities, and computed tomography revealed predominantly peripheral ground-glass opacifications. The patient's symptoms gradually improved over 48 h and imaging of the chest was unremarkable one week later. The pathophysiology, diagnosis and treatment of this rare but potentially lifethreatening complication of intravenous oil injection are discussed. PMID- 22059185 TI - Coinfection with Cryptococcus gattii and Mycobacterium tuberculosis in an otherwise healthy 18-year-old woman. AB - A case of Cryptococcus gattii (pulmonary and central nervous system) and Mycobacterium tuberculosis (pulmonary) coinfection in an otherwise healthy young woman is reported. The patient presented with a two-month history of dry cough. She had an unremarkable medical history. Both tuberculosis and cryptococcosis were diagnosed following bronchoscopy, and a subsequent lumbar puncture revealed C gattii in the cerebrospinal fluid. There is evidence that both M tuberculosis and C gattii may have suppressive effects on the host immune system. This suggests a mechanism by which an otherwise healthy individual developed these two infections. PMID- 22059186 TI - Burkholderia gladioli - a predictor of poor outcome in cystic fibrosis patients who receive lung transplants? A case of locally invasive rhinosinusitis and persistent bacteremia in a 36-year-old lung transplant recipient with cystic fibrosis. AB - There have been very few reports describing postlung transplant outcomes in patients' infected/colonized with Burkholderia gladioli pretransplant. A case involving a lung transplant recipient with cystic fibrosis who ultimately died as a result of severe rhinosinusitis due to B gladioli infection in the context of postlung transplant immunosuppression is reported. PMID- 22059187 TI - Transient elevation of the ipsilateral hemidiaphragm associated with pneumonia. AB - Seventeen children with lobar or segmental pneumonia and ispilateral elevation of the diaphragm are described. These children did not differ significantly with respect to clinical and laboratory findings from their counterparts with pneumonia but without elevation of the hemidiaphragm. The elevation was transient and resolved by the time the repeat chest x-ray was taken six to eight weeks later. PMID- 22059188 TI - Yellow nail syndrome: dystrophic nails, peripheral lymphedema and chronic cough. AB - A case involving a 41-year-old man with yellow nail syndrome (YNS) is reported. YNS is a rare disorder characterized by yellow, dystrophic nails, peripheral lymphedema and bronchiectasis with recurrent lower respiratory tract infections. YNS is often misdiagnosed because the syndrome is not well known. An interdisciplinary approach is required to recognize and collate the components of the syndrome accurately. Correct diagnosis is of utmost clinical importance because YNS can occur secondary to malignancies and autoimmune disorders. Hence, the diagnosis of YNS must prompt further investigation. PMID- 22059189 TI - A milestone achieved. PMID- 22059191 TI - Examining nurse empathy for infant procedural pain: Testing a new video measure. AB - BACKGROUND: Research reporting effective pain care strategies exists, yet it is not translated to care. Little is known about how repeated pain exposure has affected nurses' ability to be empathetic and use their knowledge to provide evidence-based care. Concerns have been raised regarding the validity of self report empathy instruments; therefore, a novel video program was developed for testing. It was hypothesized that those who viewed infants in painful and nonpainful states would have a measureable empathy (pain rating) response correlating to the level of pain expressed by the infants. OBJECTIVE: To validate the newly developed Empathy for Infant Pain video program (EIPvp) by determining whether nurse and non-nurse control groups' pain scores of 24 video clips showing infants undergoing real medical procedures were equal. DESIGN: A descriptive cross-sectional video judgement study. METHODS: Fifty female participants (25 nurses and 25 allied health controls) were asked to score the infant procedural pain level displayed in the EIPvp using a visual analogue scale and a composite score of known infant pain cues. Participants also scored their own sensitivity to painful events. RESULTS: Participants rated the videos contained in the EIPvp similarly in three categories (no, low or high pain); however, there were consistent differences between groups within the categories. Nurses scored facial cues for all categories higher than the control group. Nurses scored their own pain in hypothetical situations and that of the infants consistently higher than the control group. CONCLUSION: The EIPvp yielded predictable responses from both the nurse and non-nurse control groups when scoring the pain expressed in the video clips. Nurses' detection of pain more often than controls may have been an indication that they have greater knowledge of pain cues, or their empathy levels may have been different as a result of their exposure to, or their perceived relationship with, patients. The EIPvp was validated and has promising potential for training and research purposes. PMID- 22059192 TI - The influence of culture on maternal soothing behaviours and infant pain expression in the immunization context. AB - OBJECTIVE: To investigate how maternal culture (ie, individualist versus collectivist) influences soothing techniques and infant distress. METHODS: Archival data were analyzed using a subsample of 80 motherinfant dyads selected from a larger database of infant pain expression. RESULTS: Mothers belonging to the individualist group used more affection behaviours when attempting to regulate their infants' distress. No differences were observed in mothers' touching, holding, rocking, vocalizing, caregiving or distracting their infants. Mothers' culture did not appear to be related to the level of distress expressed by their infants. CONCLUSIONS: These results suggest that the similarities in soothing and infant pain expression between individualist and collectivist cultures are more prominent than their differences. PMID- 22059193 TI - Improving the usefulness of the Multidimensional Pain Inventory. AB - BACKGROUND: The Multidimensional Pain Inventory (MPI) is a reliable and valid self-report instrument that measures the impact of pain on an individual's life, quality of social support and general activity. Criticism of the MPI has focused on this instrument's internal structure and the stability of its classification taxonomy. OBJECTIVES: To determine whether empirical summary scales could be developed for the MPI based on a large sample of respondents diagnosed with fibromyalgia syndrome. It was hypothesized that summary scales would improve the psychometric quality of the MPI and increase the stability of respondents' taxonomy profiles across time. METHODS: Respondents completed the MPI on two occasions before their admission to a multidisciplinary pain management program. RESULTS AND CONCLUSIONS: Based on principal components analysis, three summary scales were developed that reflected level of impairment, social support and activity. Summary scales possessed good psychometric qualities and, when cluster analyzed, replicated the MPI taxonomy. Exploratory analyses of the MPI taxonomy revealed that goodness-of-fit values generally became less reliable as respondent profiles approached the overall sample mean. When the relative distance between respondents fit to taxonomy profiles and the distance from the sample mean was considered, profile stability using summary scales was predicted with good precision. These results suggest that summary scales may enhance the usefulness of the MPI, and that the traditional method of determining profile fit within the MPI is not stable and needs to be reconsidered. PMID- 22059194 TI - Post hoc analyses of data from a 90-day clinical trial evaluating the tolerability and efficacy of tapentadol immediate release and oxycodone immediate release for the relief of moderate to severe pain in elderly and nonelderly patients. AB - OBJECTIVE: To evaluate the tolerability and efficacy of tapentadol immediate release (IR) and oxycodone IR for relief of moderate to severe pain in elderly and nonelderly patients. METHODS: Post hoc data analyses were conducted on a 90 day randomized, phase 3, double-blind, flexible-dose study (ClinicalTrials.gov: NCT00364546) of adults with moderate to severe lower back pain or osteoarthritis pain who received tapentadol IR 50 mg or 100 mg, or oxycodone HCl IR 10 mg or 15 mg every 4 h to 6 h as needed for pain relief. Treatment-emergent adverse events and study discontinuations were recorded. RESULTS: Data from 849 patients randomly assigned (4:1 ratio) to treatment with a study drug (tapentadol IR [n=679] or oxycodone IR [n=170]) were analyzed according to age (younger than 65 years of age [nonelderly], or 65 years of age or older [elderly]) and treatment group. Among elderly patients, incidences of constipation (19.0% versus 35.6%) and nausea or vomiting (30.4% versus 51.1%) were significantly lower with tapentadol IR versus oxycodone IR (all P<0.05). Initial onsets of nausea and constipation occurred significantly later with tapentadol IR versus oxycodone IR (both P<=0.031). Tapentadol IR-treated elderly patients had a lower percentage of days with constipation than oxycodone IR-treated patients (P=0.020). For tapentadol IR- and oxycodone IR-treated elderly patients, respectively, incidences of study discontinuation due to gastrointestinal treatment-emergent adverse events were 15.8% and 24.4% (P=0.190). Tapentadol IR and oxycodone IR provided similar pain relief, with no overall age-dependent efficacy differences (mean pain scores [11-point numerical rating scale] decreased from 7.0 and 7.2 at baseline, to 4.9 and 5.2 at end point, respectively). CONCLUSIONS: Tapentadol IR was safe and effective for the relief of lower back pain and osteoarthritis pain in elderly patients, and was associated with a better gastrointestinal tolerability profile than oxycodone IR. PMID- 22059195 TI - Representations of OxyContin in North American newspapers and medical journals. AB - BACKGROUND: There are public concerns regarding OxyContin (Purdue Pharma, Canada) and charges within the pain medicine community that media coverage of the drug has been biased. OBJECTIVE: To analyze and compare representations of OxyContin in medical journals and North American newspapers in an attempt to shed light on how each contributes to the 'social problem' associated with OxyContin. METHODS: Using searches of newspaper and medical literature databases, two samples were drawn: 924 stories published between 1995 and 2005 in 27 North American newspapers, and 197 articles published between 1995 and 2007 in 33 medical journals in the fields of addiction/substance abuse, pain/anesthesiology and general/internal medicine. The foci, themes, perspectives represented and evaluations of OxyContin presented in these texts were analyzed statistically. RESULTS: Newspaper coverage of OxyContin emphasized negative evaluations of the drug, focusing on abuse, addiction, crime and death rather than the use of OxyContin for the legitimate treatment of pain. Newspaper stories most often conveyed the perspectives of law enforcement and courts, and much less often represented the perspectives of physicians. However, analysis of physician perspectives represented in newspaper stories and in medical journals revealed a high degree of inconsistency, especially across the fields of pain medicine and addiction medicine. CONCLUSION: The prevalence of negative representations of OxyContin is often blamed on biased media coverage and an ignorant public. However, the proliferation of inconsistent messages regarding the drug from physicians plays a role in the drug's persistent status as a social problem. PMID- 22059196 TI - Treatment of neuropathic pain with 5% lidocaine-medicated plaster: Five years of clinical experience. AB - BACKGROUND: Neuropathic pain is often severe and adversely affects patients' quality of life. OBJECTIVE: To perform a retrospective, observational study investigating the efficacy and safety of treating refractory chronic neuropathic pain with 5% lidocaine-medicated plaster, in patients attending pain centres. METHODS: Medical records from 467 patients treated with 5% lidocaine-medicated plaster were evaluated for efficacy (maximum and minimum pain intensities and coanalgesic consumption) and adverse events. Data from an initial assessment and at least one follow-up visit had to be available, and separate analyses were conducted for the general population and the subpopulation older than 70 years of age. RESULTS: Of the patients enrolled, 25.0% were older than 70 years of age. While 20.6% had postherpetic neuralgia, 76.3% had other types of peripheral pain. Approximately 78.1% of cases of peripheral neuropathic pain followed surgery, and 23% were post-traumatic pain. The time from onset to referral was more than one year in two- thirds of cases. All patients experienced pain of at least moderate severity (mean [+/- SD] 11-point numerical rating scale score 5.2 +/- 2.4 to 8.2 +/- 1.6). Treatment with 5% lidocaine-medicated plaster reduced pain intensity by more than 50% in 45.5% of patients, and by at least 30% in 82.2%. Of note, the consumption of analgesics and coanalgesics was significantly reduced. Results were similar in both the general population and the subpopulation older than 70 years of age, at high risk and often receiving multiple medications. CONCLUSIONS: Treatment of refractory neuropathic pain with 5% lidocaine-medicated plaster clearly demonstrated efficacy and an excellent safety profile in patients with refractory neuropathic pain. PMID- 22059198 TI - Catastrophizers with chronic pain display more pain behaviour when in a relationship with a low catastrophizing spouse. AB - The present study examined the relationship between couple concordance of catastrophizing and adverse pain outcomes. Possible mechanisms underlying the relationship between couple concordance of catastrophizing and pain outcomes were also explored. Fifty-eight couples were recruited for the study. The chronic pain patients were filmed while lifting a series of weighted canisters. The spouse was later invited to view the video and answer questions about the pain experience of their partner. Median splits on Pain Catastrophizing Scale scores were used to create four 'catastrophizing concordance' groups: low catastrophizing patient-low catastrophizing spouse; low catastrophizing patient-high catastrophizing spouse; high catastrophizing patient-low catastrophizing spouse; and high catastrophizing patient-high catastrophizing spouse. Analyses revealed that high catastrophizing pain patients who were in a relationship with a low catastrophizing spouse displayed more pain behaviours than patients in all other groups. These findings suggest that high catastrophizing chronic pain patients may need to increase the 'volume' of pain communication to compensate for low catastrophizing spouses' tendency to underestimate the severity of their pain experience. Patients' perceived solicitousness and punitive response from the spouse could not explain the group differences in pain behaviour. Theoretical and clinical implications of the findings are discussed. PMID- 22059200 TI - Persistent pain in a community-based sample of children and adolescents. AB - BACKGROUND: Very few studies have investigated the psychological factors associated with the pain experiences of children and adolescents in community samples. OBJECTIVES: To examine the lifetime prevalence of, and psychological variables associated with, persistent pain in a community sample of children and adolescents, and to explore differences according to sex, age and pain history. METHODS: Participants completed the Childhood Anxiety Sensitivity Index (CASI), the Child Pain Anxiety Symptoms Scale (CPASS), the Multidimensional Anxiety Scale for Children-10 (MASC-10), the Pain Catastrophizing Scale for Children (PCS-C) and a pain history questionnaire that assessed chronicity and pain frequency. After research ethics board approval, informed consent/assent was obtained from 1022 individuals recruited to participate in a study conducted at the Ontario Science Centre (Toronto, Ontario). RESULTS: Of the 1006 participants (54% female, mean [+/- SD] age 11.6+/-2.7 years) who provided complete data, 27% reported having experienced pain that lasted for three months or longer. A 2*2*2 (pain history, age and sex) multivariate ANOVA was conducted, with the total scores on the CASI, the CPASS, the MASC-10 and the PCS-C as dependent variables. Girls with a history of persistent pain expressed higher levels of anxiety sensitivity (P<0.001) and pain catastrophizing (P<0.001) than both girls without a pain history and boys regardless of pain history. This same pattern of results was found for anxiety and pain anxiety in the older, but not the younger, age group. CONCLUSIONS: Boys and girls appear to differ in terms of how age and pain history relate to the expression of pain-related psychological variables. Given the prevalence of persistent pain found in the study, more research is needed regarding the developmental implications of persistent pain in childhood and adolescence. PMID- 22059201 TI - Opioid analgesics suppress male gonadal function but opioid use in males and females does not correlate with symptoms of sexual dysfunction. AB - BACKGROUND: Opioid analgesia impairs gonadal function in men and women, but the correlation with symptoms and hormonal measurements of hypogonadism is not well established. OBJECTIVE: To determine the frequency of impaired gonadal function in men and women using opioids for chronic pain, and to determine the correlation of symptoms with hormonal measurements of gonadal function. METHODS: A prospective study of patients attending a multidisciplinary pain clinic was conducted. A total of 65 women (47 opioid users and 18 nonopioid analgesic controls) and 32 men (26 opioid users and six controls) were enrolled. Histories of sexual dysfunction and hormonal testing (men: total testosterone [TT], free testosterone [FT], prolactin and luteinizing hormone; women: FT, TT, prolactin, dehydroepiandrosterone sulphate, sex hormone- binding globulin, progesterone, luteinizing hormone and follicle- stimulating hormone, and estradiol) were obtained. RESULTS: In men, a low FT level was more common in opioid users (20/26; P=0.04). In men with abnormal hormone levels, there was no difference in the frequency of sexual dysfunction compared with men with normal hormone levels, and no difference in the frequency of opioid versus nonopioid use. In women, opioid users had lower FT levels (P=0.02). Low dehydroepiandrosterone sulphate was more frequent in women on opioids (P=0.03) in the menopausal group only (P=0.046). Premenopausal women taking opioids more frequently had a low TT level (P=0.03). The frequency of female sexual dysfunction was the same in opioid users (32/47) and controls (13/18; P=0.75), and also did not relate to any hormone abnormality. DISCUSSION: Men taking opioids had lower FT and higher prolactin levels, and women taking opioids had lower FT levels. Frequency of sexual dysfunction did not correlate with hormone levels in either men or women taking opioids. CONCLUSION: Opioids frequently cause low FT levels in men, but there is no relationship between abnormal hormone levels and symptoms of sexual dysfunction. Therefore, all men should be screened for low FT levels. Women on opioids had lower FT levels, but this did not correlate with sexual dysfunction symptoms. Therefore, measurements of FT or other hormones were not considered to be useful in women. PMID- 22059202 TI - Current states of opinion and future directions on the epidemiology of sex differences in human pain. AB - One of the most commonly neglected findings in the human pain literature is the observation of sex differences in the mechanisms that support the phenotypic expression of pain. The present commentary describes an assessment of the prevalence of observed sex differences in various pain processes, and of how expert pain researchers interpret the epidemiology and, hence, the proximate and ultimate causes of such differences. Forty-two pain investigators completed an anonymous survey on the epidemiology of sex differences in the human pain experience. Investigator responses indicated that sex differences are pervasive across various areas of pain research, that sex differences are particularly pronounced in the area of situational influences on pain behaviors, and that contemporary pain researchers largely disagree on the epidemiology of, and hence, proximate and ultimate causes of the differences. The relevance of social situational factors on sex differences in pain behaviours is discussed in the context of evolutionary, developmental, social psychology and pain sensory systems that may function, in part, for regulating interpersonal intimacy. PMID- 22059203 TI - Pain control in infants and young children. PMID- 22059204 TI - Nonpharmacological management of procedural pain in infants and young children: an abridged Cochrane review. AB - BACKGROUND: Acute pain and distress during medical procedures are commonplace for young children. OBJECTIVE: To assess the efficacy of nonpharmacological interventions for acute procedural pain in children up to three years of age. METHODS: Study inclusion criteria were: participants <3 years of age, involved in a randomized controlled or crossover trial, and use of a 'no treatment' control group (51 studies; n=3396). Additional studies meeting all criteria except for study design (eg, use of active control group) were qualitatively described (n=20). RESULTS: For every intervention, data were analyzed separately according to age group (preterm-born, term-born neonate and older infant / young child) and type of pain response (pain reactivity, immediate pain-related regulation). The largest standardized mean differences (SMD) for pain reactivity were as follows: sucking-related interventions (preterm: -0.42 [95% CI -0.68 to -0.15]; neonate 1.45 [CI -2.34 to -0.57]), kangaroo care (preterm -1.12 [95% CI -2.04 to -0.21]), and swaddling / facilitated tucking (preterm -0.97 [95% CI -1.63 to -0.31]). For immediate pain-related regulation, the largest SMDs were: sucking-related interventions (preterm -0.38 [95% CI -0.59 to -0.17]; neonate -0.90 [CI -1.54 to 0.25]), kangaroo care 0.77 (95% CI -1.50 to -0.03]), swaddling / facilitated tucking (preterm -0.75 [95% CI -1.14 to -0.36]), and rocking / holding (neonate 0.75 [95% CI -1.20 to -0.30]). The presence of significant heterogeneity limited confidence in nonsignificant findings for certain other analyses. CONCLUSIONS: Although a number of nonpharmacological treatments have sufficient evidence supporting their efficacy with preterm infants and healthy neonates, no treatments had sufficient evidence to support efficacy with healthy older infants / young children. PMID- 22059205 TI - Cerebral near-infrared spectroscopy as a measure of nociceptive evoked activity in critically ill infants. AB - Signs of pain may be subtle or absent in a critically ill infant. The complex nature of pain may further obscure its identification and measurement. Because the use of monitoring and neuroimaging techniques has become more common in pain research, an understanding of these specialized technologies is important. Near infrared spectroscopy (NIRS) is a noninvasive technique for monitoring tissue hemodynamics and oxygenation. There are indications that NIRS is capable of detecting the cerebral hemodynamic changes associated with sensory stimuli, including pain, in infants. These developments suggest that NIRS may play an important role in research focusing on pain perception in critically ill infants. The present review briefly describes the cortical responses to noxious stimuli, which parallel cerebral hemodynamic responses to various stimuli. This is followed by an overview of NIRS technology including a summary of the literature on functional studies that have used NIRS in infants. Current NIRS techniques have well-recognized limitations that must be considered carefully during the measurement and interpretation of the signals. Nonetheless, until more advanced NIRS techniques emerge, the current devices have strengths that should be exploited. PMID- 22059206 TI - A comparison between enriched and nonenriched enrollment randomized withdrawal trials of opioids for chronic noncancer pain. AB - BACKGROUND: An enriched enrollment randomized withdrawal (EERW) design excludes potential participants who are nonresponders or who cannot tolerate the experimental drug before random assignment. It is unclear whether EERW design has an influence on the efficacy and safety of opioids for chronic noncancer pain (CNCP). OBJECTIVES: The primary objective was to compare the results from EERW and non-EERW trials of opioids for CNCP. Secondary objectives were to compare weak versus strong opioids, subgroups of patients with different types of pain, and the efficacy of opiods compared with placebo versus other drugs. METHODS: MEDLINE, EMBASE and CENTRAL were searched up to July 2009, for randomized controlled trials of any opioid for CNCP. Metaanalyses and meta-regressions were conducted to compare the results. Treatment efficacy was assessed by effect sizes (small, medium and large) and the incidence of adverse effects was assessed by a clinically relevant mean difference of 10% or greater. RESULTS: Sixty-two randomized trials were included. In 61 trials, the duration was less than 16 weeks. There was no difference in efficacy between EERW and non-EERW trials for both pain (P=0.6) and function (P=0.3). However, EERW trials failed to detect a clinically relevant difference for nausea, vomiting, somnolence, dizziness and dry skin/itching compared with non-EERW. Opioids were more effective than placebo in patients with nociceptive pain (effect size=0.60, 95% CI 0.49 to 0.72) and neuropathic pain (effect size=0.56, 95% CI 0.38 to 0.73). CONCLUSION: EERW trial designs appear not to bias the results of efficacy, but they underestimate the adverse effects. The present updated meta- analysis shows that weak and strong opioids are effective for CNCP of both nociceptive and neuropathic origin. PMID- 22059207 TI - Postoperative respiratory depression with pregabalin: a case series and a preoperative decision algorithm. AB - Pregabalin is gaining popularity in the perioperative period for its usefulness in treating neuropathic pain and its apparent opioid- sparing effect. The present report describes the perioperative course of three patients who received pregabalin and experienced significant respiratory depression in the postoperative period. All three patients consented to the report and publication of the present case series. The first patient was elderly with borderline renal dysfunction. She experienced respiratory arrest in the immediate postoperative period following a craniotomy for tumour excision. The second patient presented with severe respiratory depression 12 h after receiving a spinal anesthetic for joint replacement, and was later found to have clinically significant obstructive sleep apnea. The third patient, who was an otherwise healthy elderly individual on benzodiazepines for anxiety, experienced respiratory arrest in the postanesthesia care unit after an uneventful anesthesia for lumbar spine decompression. All of these patients were treated successfully with standard resuscitation measures. Although other causes of respiratory depression in these patients were considered, there appears to be an association between pregabalin and this complication. The present article briefly reviews the evidence regarding the perioperative use of pregabalin. Based on the authors' experience and the available evidence, they believe that pregabalin may be useful in the management of acute pain in carefully selected patients undergoing certain surgeries. A clinical algorithm has been developed to guide the perioperative use of pregabalin. This algorithm may be helpful in increasing the safety of perioperative pregabalin use. PMID- 22059208 TI - Identification of a persistent primitive trigeminal artery following the transposition technique for trigeminal neuralgia: a case report. AB - A patient who presented with trigeminal neuralgia associated with a persistent primitive trigeminal artery (PPTA) is presented. A 62-year-old woman suffering from right orbital pain was admitted to the hospital. Medical treatment for three months was ineffective, and her neuralgia had deteriorated and gradually spread in the maxillary division. Magnetic resonance imaging demonstrated the flow void signal attached to the right trigeminal nerve. Thus, microvascular decompression was performed. The superior cerebellar artery was the responsible artery, and it was transposed to decompress the trigeminal nerve. After this manoeuvre, an artery was identified running parallel to the trigeminal nerve toward Meckel's cave. The artery, which turned out to be a PPTA, communicated with the basilar artery. The PPTA was carefully observed, and it was found not to be the artery causing the neuralgia because it did not compress the nerve at surgical observation. No additional procedure between the PPTA and the trigeminal nerve was performed. The patient's symptom improved dramatically following surgery, and her postoperative course was uneventful. Postoperative three-dimensional computed tomography showed the PPTA. The findings in the present case suggest that transposition of the responsible artery effectively decompresses the root entry zone and assists in determining whether the PPTA is affecting the trigeminal nerve. PMID- 22059209 TI - Asking the important questions. PMID- 22059210 TI - Unintended pregnancies - Reducing rates by improving access to contraception. AB - Unintended pregnancies have significant social, health and financial costs. Importantly, there is surprisingly little information available about the prevalence of unintended pregnancy in Australia. We are currently investigating unintended pregnancy and access to contraception among women aged 18-23 years in rural and urban areas of New South Wales. This is the first step toward understanding how access to effective contraception can be improved and could act as a pilot study for a regular survey of fertility. PMID- 22059211 TI - Intimate partner violence - identification and response in general practice. AB - BACKGROUND: Intimate partner violence is a common problem among women attending general practice, with around one in 10 women currently experiencing physical, sexual or emotional abuse by a partner. Abused women frequently present with physical and psychosocial issues. Yet intimate partner violence often remains concealed and addressing it poses challenges for the clinician and patient alike. OBJECTIVE: Although some of the general recommendations in this review may also apply to same-sex relationships and to women who abuse men, this article discusses identifying intimate partner violence in women who present to general practice. DISCUSSION: Identifying intimate partner violence is important in clinical practice as it underlies many common physical and mental health presentations. Facilitating disclosure and responding effectively requires good communication skills. Safety assessment of women and their families, pinpointing level of readiness to contemplate action, and providing appropriate referral options and ongoing nonjudgmental support are elements of an effective response. General practitioners have the potential to identify women and support them safely on a pathway to recovery, thereby avoiding the long term impacts of intimate partner violence. PMID- 22059212 TI - Nonaccidental injury in childhood. AB - BACKGROUND: Nonaccidental injury is a significant cause of mortality and morbidity, especially in infants and young children. OBJECTIVE: This article focuses on physical injuries that are commonly observed when children have been physically harmed as a result of abuse and neglect. DISCUSSION: In 2009-2010 statutory child protection agencies in Australia received 187 314 notifications regarding suspected child abuse and neglect, of which 31 295 were substantiated. Substantiated child abuse and neglect occurred for 6.1 per 1000 Australian children. The good news is that these data represent a 10% reduction in the number of notifications and a 4% reduction in the number of substantiated reports compared to 2008-2009 data. Children are vulnerable and child abuse is common. It is therefore important for all general practitioners to be skilled in recognising and responding to child abuse and neglect. PMID- 22059213 TI - Benzodiazepines - Their role in aggression and why GPs should prescribe with caution. AB - BACKGROUND: Benzodiazepines are widely prescribed in Australia, despite concerns about their potential for abuse and dependence. Paradoxical reactions, disinhibition and amnesia are all associated with benzodiazepine use, misuse and intoxication. While violent and aggressive behaviour may be a consequence of such disinhibition, there is limited information available regarding the links between benzodiazepine use and violence. OBJECTIVE: This article aims to examine the existing evidence on the relationship between benzodiazepines, violence and aggression. DISCUSSION: While current evidence suggests that benzodiazepines rarely induce violence, it is important to note that the available literature is limited in its scope and that benzodiazepine related violence is often severe and of potential concern to frontline workers. Mediating risk factors for benzodiazepine related violence include concurrent alcohol use, benzodiazepine dose, a history of aggression and underlying impulsivity. Comprehensive assessment and alternate nonpharmacological treatment options should be considered before prescribing benzodiazepines within primary care. PMID- 22059214 TI - Aggressive behaviour - prevention and management in the general practice environment. AB - BACKGROUND: Aggressive behaviour is commonly encountered in the general practice setting and can often be de-escalated using good communication skills. OBJECTIVE: This article provides strategies to reduce and manage early aggression in the general practice environment. DISCUSSION: Aggressive behaviour usually occurs when a person feels unfairly treated. Having a systematic approach to the problem can improve safety for both staff and patients. This includes patient centred practice, identifying and managing the early signs of aggression to prevent escalation, having a plan to seek assistance if required, setting limits using a calm respectful manner and reinforcing limits using behaviour contracts when required. The physical layout of the practice and restraint of aggressive people are beyond the scope of this article. PMID- 22059215 TI - The prepubertal hymen. AB - Not so long ago, some doctors believed that they could determine, on the basis of examination of a girl's genitals, whether or not the girl had engaged in sexual intercourse. Even today, 'virginity checks' are conducted by doctors in some countries. Some Australian doctors still believe that it should be possible to determine, on the basis of examination findings, whether a child has been sexually abused. This article sets out to describe some of the common variations in hymenal anatomy in order to dispel myths and misperceptions surrounding genital examination findings in young girls. PMID- 22059216 TI - Ambulatory blood pressure monitoring. AB - This article forms part of our 'Tests and results' series for 2011 which aims to provide information about common tests that general practitioners order regularly. It considers areas such as indications, what to tell the patient, what the test can and cannot tell you, and interpretation of results. PMID- 22059217 TI - Primary hyperparathyroidism - is vitamin D supplementation safe? AB - BACKGROUND: Vitamin D deficiency is commonly seen in patients with primary hyperparathyroidism. However, there is a widespread reluctance to provide vitamin D supplementation to this group of patients. OBJECTIVE: This article examines the relationship between vitamin D deficiency and primary hyperparathyroidism and the effects of vitamin D supplementation. CONCLUSION: Vitamin D deficiency exacerbates primary hyperparathyroidism and vice versa. With care, vitamin D supplementation can safely be given to selected patients with asymptomatic primary hyperparathyroidism and is suggested before deciding on medical or surgical management. Monitoring serum calcium concentration and urinary calcium excretion is recommended while achieving vitamin D repletion. PMID- 22059218 TI - Obstructive sleep apnoea and snoring - is examination necessary? AB - This article outlines two cases of snoring and obstructive sleep apnoea (OSA) secondary to parapharyngeal space tumours. Both patients were referred to a specialist sleep clinic where oropharyngeal masses were seen and biopsied. Both underwent surgery and this was curative of both their snoring and their OSA. Parapharyngeal space tumours are an extremely rare cause of OSA and snoring. However, all patients with OSA and snoring should have a full head and neck examination before referral; in rare cases this could enable early detection of a parapharyngeal space tumour. PMID- 22059219 TI - Steroid associated infective keratitis - case studies for caution. PMID- 22059220 TI - Occupational violence. AB - The problem of violence directed toward general practitioners and their practice staff is acknowledged worldwide. In Australia, the tragic 2006 murder of a Melbourne GP while practising in her surgery highlighted the seriousness of the issue. PMID- 22059221 TI - Patient centred care - are international medical graduates 'expert novices'? AB - BACKGROUND: Depending on their previous training, international medical graduates (IMGs) may be unfamiliar with patient centred care (PCC). This study explores the PCC skills that IMGs demonstrated during observed role play. METHODS: Qualitative observational data were collected during an IMG communication skills course and IMGs' perceptions of PCC were explored in semistructured interviews. Analysis followed principles of grounded theory and focused specifically on the elements of Candlin's (2002) quality of discourse. RESULTS: Many of the IMGs observed in this study used discourse features that identify them as novices in PCC: they framed consultations as interviews as opposed to conversations, maintained topic control instead of allowing digressions, and focused on achieving simple coherence rather than seeing the consultation as a whole. DISCUSSION: This study suggests that some IMGs may be novices in PCC while being experts in medical knowledge. A view of IMGs as 'expert novices' may be useful to inform the development of bridging courses. PMID- 22059222 TI - Lifestyle intervention - a study on maintenance in general practice. AB - AIM: This article aims to explore the factors contributing to sustained or nonsustained behaviour change following a lifestyle intervention in general practice. METHODS: Twenty patients who had participated in a general practice health check and group lifestyle support program were interviewed by telephone after 12 months. The interviews were transcribed and analysed thematically. RESULTS: Patients reported positive effects of the intervention on their behaviour change, especially the group peer support. However, their maintenance of these changes varied. Factors that contributed to sustained behaviour change included social support and self efficacy. Factors contributing to relapse included competing demands on time, comorbidity and stress. DISCUSSION: Greater attention needs to be given to maintenance of behaviour change in lifestyle management programs. Following completion of the program, there needs to be greater support for relapse prevention and management and effective integration back into general practice. PMID- 22059223 TI - Treating chronic fatigue syndrome - a study into the scientific evidence for pharmacological treatments. AB - BACKGROUND: Chronic fatigue syndrome, or myalgic encephalomyelitis (CFS), is a severe disabling condition. Patients with CFS usually trial many different medicines, both conventional and complementary. An overview of the pharmacological treatments used by CFS patients and the available evidence underpinning the use of these treatments would be of great value to both patients and their healthcare providers. METHODS: Ninety-four CFS patients recruited into an Australian study investigating immunological biomarkers filled out a questionnaire assessing the medicines they were taking. Evidence from randomised clinical trials was sought in biomedical databases. RESULTS: The 94 CFS patients used 474 different medicines and supplements. The most commonly used medicines were antidepressants, analgesics, sedatives, and B vitamins. We identified 20 randomised controlled trials studying these medicines in CFS patients. DISCUSSION: While conventional and complementary medicines are widely used by CFS patients, the evidence for effectiveness in CFS is very limited. PMID- 22059224 TI - Web based diabetes care planning - sociotechnical barriers to implementation in general practice. AB - BACKGROUND: This research explored the sociotechnical barriers in the implementation of web based diabetes care plans in general practice from the perspective of implementing stakeholders. METHODS: A qualitative case study design was use to explore the sociotechnical barriers. Twenty-one stakeholders were purposely recruited and interviewed. RESULTS: Technological barriers included rudimentary IT applications in general practice; standardisation and interoperability issues; and 'bugs' in the system. The role of practice managers as gatekeepers influenced the uptake of the technology. General practitioners were noted to be time poor, while practice nurses preferred to stick with paper based ways of doing care plans. The relationship between allied health professionals and GPs also influenced the adoption process. DISCUSSION: Implementers had significant insight into the sociotechnical barriers to diabetes web based care planning in general practice. Future research should examine the roles of the stakeholders involved in determining standards and the interoperability of systems. PMID- 22059225 TI - Child abuse - mandatory reporting requirements. AB - All Australian states and territories have legislation that requires medical practitioners to report cases of child abuse to the appropriate child protection service. This article outlines the obligations of medical practitioners to report child abuse and highlights the differences that exist in the legislative requirements in each state and territory. PMID- 22059226 TI - Advanced rural skills training - the value of an addiction medicine rotation. AB - BACKGROUND: General practitioners are ideally placed to address drug and alcohol problems in the Australian population. Lack of adequate undergraduate and postgraduate training has been suggested as a key barrier limiting their involvement in addiction medicine. OBJECTIVE: This article describes the establishment and operations of an advanced rural skills training program at the Lyndon Community - a rural drug and alcohol treatment organisation in New South Wales. DISCUSSION: An addiction medicine rotation offers general practice registrars the opportunity to develop skills and experience in psychosocial interventions as well as physical and mental health issues common in the treatment population. Registrars participating in the Lyndon Community program perceived that the training period had influenced and enhanced their future practice. PMID- 22059227 TI - Fitness to drive forms - a guide for GPs. AB - The effect of medical conditions on fitness to drive and crash risk has long been recognised. Therefore doctors and other health professionals play an important role in public health and safety when advising patients about fitness to drive and when providing information to driver licensing authorities to support their decision making in this regard. Various forms support communication between the doctor, patient and driver licensing authority. PMID- 22059228 TI - Rapid detection of apoptosis in mammalian cells by using intact cell MALDI mass spectrometry. AB - Detection of cell death has extensive applications and is of great commercial value. However, most current high-throughput cell viability assays cannot distinguish the two major forms of cell death: apoptosis and necrosis. Many apoptosis-specific detection methods exist but they are time consuming and labour intensive. In this work, we proposed a novel approach based on Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) for the specific detection of apoptosis in cultured mammalian cells. Buffer washed cells were directly mixed with a matrix solution and subsequently deposited onto the stainless steel target for MALDI analysis. The resulting mass spectrometric profiles were highly reproducible and can be used to reflect cell viability. Remarkably, the mass spectrometric profiles generated from apoptotic cells were distinct from those from either normal or necrotic cells. The apoptosis-specific features of the mass spectra were proportional to the percentage of apoptotic cells in the culture, but are independent of the drugs used to stimulate apoptosis. This is the first report on the utilization of intact cell MALDI mass spectrometry in detecting mammalian cell apoptosis, and can be used as a basis for the development of a reliable, fast, label-free and high-throughput method for detecting apoptotic cell death. PMID- 22059229 TI - Sensitive and selective voltammetric measurement of Hg2+ by rational covalent functionalization of graphene oxide with cysteamine. AB - We report here a new voltammetric method for the sensitive and selective determination of Hg(2+) based on rational covalent functionalization of graphene oxide with cysteamine to form cysteamine-functionalized graphene through nucleophilic ring-opening reaction between the epoxy of graphene oxide and the amino group of cysteamine in KOH solution. PMID- 22059230 TI - A highly effective polymerase chain reaction enhancer based on dendrimer entrapped gold nanoparticles. AB - In molecular biology, polymerase chain reaction (PCR) has played an important role but suffers a general problem of low efficiency and specificity. Development of suitable PCR additives to improve the specificity and efficiency still remains a great challenge. Here we report the use of dendrimer-entrapped gold nanoparticles (Au DENPs) as a novel class of enhancers to improve the specificity and efficiency of PCR. We show that the Au DENPs prepared using amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH(2)) as templates are much more effective than the same dendrimers without AuNPs entrapped in improving the specificity and efficiency of an error-prone two-round PCR system. With the increase of the molar ratio between Au atom and G5.NH(2) dendrimer in the Au DENPs, the optimum concentration of Au DENPs used to improve the PCR specificity and efficiency is decreased and can be as low as 0.37 nM when the Au atom/G5.NH(2) dendrimer molar ratio reaches 100:1. Our PCR results along with the dynamic light scattering data suggest that unlike the flexible soft dendrimers without NPs entrapped that may display a non-spherical shape when interacting with the PCR components, the Au DENPs with increasing Au atom/dendrimer molar ratio are able to reserve the spherical shape of dendrimers, enabling much more efficient interaction with the PCR components. Therefore, as a NP-based PCR enhancer, both the surface charge and the shape of the particles should be responsible for effective interaction with the PCR components for improving the PCR specificity and efficiency. Furthermore, the used Au DENPs were proved to be stable after the PCR process, enabling them to be potentially used for enhancing different PCR systems. PMID- 22059231 TI - Evaluation of antibacterial effect and mode of Coptidis rhizoma by microcalorimetry coupled with chemometric techniques. AB - In this study, the antibacterial effect and mode of Coptidis rhizoma on Escherichia coli was evaluated by microcalorimetry coupled with chemometric techniques. Using an isothermal microcalorimeter, the metabolic profiles of E. coli growth at 37 degrees C affected by 15 batches of C. rhizoma were measured. Through principal component analysis (PCA) on nine quantitative thermo-kinetic parameters obtained from the metabolic power-time profiles of E. coli, the antibacterial effects of C. rhizoma from various sources could be easily evaluated by analyzing the change of the two main thermo-kinetic parameters, growth rate constant k(2) and maximum heat-output power P(2)(m), in the second exponential phase of E. coli growth. Then, hierarchical clustering analysis (HCA) was carried out on the two parameters to distinguish those C. rhizoma samples in respect to their antibacterial effects. Clear results were obtained to show that all 15 C. rhizoma samples with different antibacterial effects could be successfully grouped in accordance with their origins. Ranked in decreasing order, the antibacterial mode of C. rhizoma samples that were from Sichuan province had the strongest antibacterial effects, followed by samples from Chongqing city and Hubei province. Our results revealed that the developed microcalorimetry with chemometric techniques had the potential perspective for evaluating the effect and mode of Coptidis rhizoma and other Chinese materia medicas. PMID- 22059232 TI - Polymer-capped fiber-optic Raman probe for non-invasive Raman spectroscopy. AB - Advances in fiber optic probe design are moving Raman spectroscopy into the clinic, although there remain important practical problems. While much effort has been devoted to minimizing Raman and fluorescence background from fibers, less attention has been given to the need to generate reference Raman signals that can correct for variations in tissue albedo, which is important in quantifying changes in tissue composition. To address this shortcoming, we have developed a fiber optic probe that incorporates a fluorinated ethylene-propylene copolymer (FEP) cap at the end of each excitation fiber. Transmission of laser light through the transparent cap generates a 732 cm(-1) Raman band whose intensity scales linearly with the laser power delivered to the tissue of interest. In our first design, the FEP cap functions as a waveguide with only a small insertion loss (~5%). Laser transmission through 1 mm of the polymer is sufficient to generate a usable reference Raman signal. We show the application of the probe to quantitative non-invasive Raman spectroscopy of animal tissues using rat leg phantoms as models. Ex-vivo Raman spectroscopy of excised rat tibia supports the use of the probe for spectroscopy of various tissues. These results provide proof of principle that the Raman probe can be used in multiple spectroscopic applications. PMID- 22059233 TI - Effect of HER2 status on risk of recurrence in women with small, node-negative breast tumours. AB - BACKGROUND: Adjuvant trastuzumab for small, node-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains controversial. The purpose of this study was to investigate the risk of recurrence in women with pathological tumour node (pTN) T1 N0 tumours. METHODS: Patients with pT1 N0 breast cancer diagnosed at the National Kyushu Cancer Centre between 2001 and 2007 were reviewed. Patients were categorized according to HER2 status. RESULTS: Four hundred and fifty-four patients who had pT1 N0 tumours, and had not received adjuvant trastuzumab, were identified. The HER2-negative and -positive groups comprised 376 and 78 patients (17.2 per cent) respectively. At a median follow-up of 46.3 months, there were 18 recurrences.The 5-year relapse-free survival (RFS) rates were 97.2 and 88 per cent in the HER2-negative and -positive groups respectively (P < 0.001). Multivariable analysis identified HER2-positive tumour as an independent predictor of RFS in patients with pT1 N0 tumours (hazard ratio 6.65, 95 per cent confidence interval 2.53 to 17.49; P < 0.001). CONCLUSION: Women with pT1 N0 HER2-positive breast cancer have a high risk of recurrence. PMID- 22059234 TI - Retraction: De Hert SG, Lorsomradee S, vanden Eede H, Cromheecke S, Van der Linden PJ. A randomized trial evaluating different modalities of levosimendan administration in cardiac surgery patients with myocardial dysfunction. J Cardiothorac Vasc Anesth 2008;22:699-705. PMID- 22059235 TI - Healthcare resource use and medical costs for the management of oesophageal cancer. AB - BACKGROUND: This study examined the interaction between natural history, current practice patterns in diagnosis, monitoring and treatment of oesophageal cancer, and associated health resource utilization and costs. METHODS: A cost analysis of a prospective population-based cohort of 1100 patients with a primary diagnosis of oesophageal cancer was performed using chart review from the Australian Cancer Study Clinical Follow-Up Study. The analysis enabled estimation of healthcare resources and associated costs in 2009 euros by stage of disease and treatment pathway. RESULTS: Most patients (88.5 per cent) presented with stage II, III or IV cancer; 61.1 per cent (672 of 1100) were treated surgically. Overall mean costs were ?37,195 (median ?29,114) for patients undergoing surgery and ?17,281 (median ?13,066) for those treated without surgery. Surgery contributed 66.4 per cent of the total costs (mean ?24,697 per patient) in the surgical group. In the non-surgical group, use of chemotherapy was more prevalent (81.9 per cent of patients) and contributed 61.1 per cent of the total costs. Other important cost determinants were gastro-oesophageal junction tumours, treatment location and tumour stage. Mean costs of those monitored for Barrett's oesophagus (7.3 per cent of patients) were lower, although about one-third still presented with advanced-stage cancer. CONCLUSION: Overall costs for managing oesophageal cancer were high and dominated by surgery costs in patients treated surgically and by chemotherapy costs in patients treated without surgery. Radiotherapy, treatment location and cancer subtype were also important. Monitoring for Barrett's oesophagus and earlier-stage detection were associated with lower management costs, but the potential net benefit from surveillance strategies needs further investigation. PMID- 22059236 TI - From branch to bedside: Youyou Tu is awarded the 2011 Lasker~DeBakey Clinical Medical Research Award for discovering artemisinin as a treatment for malaria. PMID- 22059237 TI - A mystery unfolds: Franz-Ulrich Hartl and Arthur L. Horwich win the 2011 Albert Lasker Basic Medical Research Award. PMID- 22059238 TI - True dedication to clinical research: the Clinical Center of the National Institutes of Health receives the 2011 Mary Woodard Lasker Award for Public Service. PMID- 22059239 TI - [Bulletin INFOVAC-France]. PMID- 22059240 TI - Person--environment fit and functioning among older adults in a long-term care setting. PMID- 22059241 TI - Assisted living nurse competencies. PMID- 22059243 TI - [Molecular probes for the diagnosis of bacteremia]. PMID- 22059242 TI - Images of health care. PMID- 22059244 TI - [Colistin for the treatment of ventilator-associated pneumonia]. PMID- 22059245 TI - [Bacteremia/fungemia associated to a peripherally inserted venous central catheter]. PMID- 22059246 TI - The context and development of a global framework for plant conservation. AB - A new international initiative for plant conservation was first called for as a resolution of the International Botanical Congress in 1999. The natural home for such an initiative was considered to be the Convention on Biological Diversity (CBD), and the Conference of the Parties (COP) to the CBD agreed to consider a Global Strategy for Plant Conservation (GSPC) at its 5th meeting in 2000. It was proposed that the GSPC could provide an innovative model approach for target setting within the CBD and, prior to COP5, a series of inter-sessional papers on proposed targets and their justification were developed by plant conservation experts. Key factors that ensured the adoption of the GSPC by the CBD in 2002 included: (1) ensuring that prior to and during COP5, key Parties in each region were supportive of the Strategy; (2) setting targets at the global level and not attempting to impose these nationally; and (3) the offer by Botanic Gardens Conservation International (BGCI) to support a GSPC position in the CBD Secretariat for 3 years, which provided a clear indication of the support for the GSPC from non-governmental organizations (NGO). PMID- 22059247 TI - What more can plant scientists do to help save the green stuff? AB - The Global Strategy for Plant Conservation (GSPC) was the first such effort under the Convention on Biological Diversity (CBD), and had gone through a 3-year process to reach the level of maturity that enabled it to be approved by consensus by all Governments present at the key session in The Hague in April 2002. It provided a model for subsequent CBD workplans, with targets, and undoubtedly contributed to the 2010 target of reducing the rate of biodiversity loss. In the event, few of the targets were achieved, because of numerous constraints at both policy and implementation levels. Even so, the GSPC stands as an important milestone in the global effort to conserve biodiversity. However, few plant scientists can be satisfied that the essential steps are being taken to ensure the conservation of plants, although, of course, plant scientists are only one part of the complex effort that will be required. This paper offers some suggestions that might be worth consideration, building on the basic principle in politics that a strong constituency is necessary to victory. In other words, although plant scientists play a crucial role, plant conservation is too important to leave in their hands alone; far broader support is required, including from the private sector, agriculture, forestry, trade, economics, tourism and even the military. Although botanical science provides a solid foundation, other branches of science are also important, ranging from anthropology to zoology. The legal profession also has important contributions to make (as well as the ability to hamper progress - for example through using issues such as access and benefit sharing to limit the exchange of genetic materials for even noncommercial use). 2010 was the United Nations Year of Biodiversity, and the GSPC targets reached their due date. It therefore seems timely to add some additional perspectives to the effort to update the GSPC. This paper suggests ways to reach a far broader constituency, provides tools to those who are expected to achieve the targets, and suggests ways to build a strong international constituency to conserve the world's botanical wealth. PMID- 22059248 TI - Strengthening the scientific contribution of botanic gardens to the second phase of the Global Strategy for Plant Conservation. AB - The need for action on the global environment is now well understood and governments, agencies, non-governmental organizations and botanic gardens have all been working in their various ways to promote environmental sustainability and reduce species and habitat loss for at least 10-20 years. The Global Strategy for Plant Conservation (GSPC) has been widely adopted, particularly by the botanic garden community, and has resulted in many successes despite failing to achieve its ultimate goal of halting the loss of plant biodiversity. The objectives and targets for Phase 2 of the GSPC, running from 2010 to 2020, mirror those of Phase 1 and had been largely agreed prior to their formal adoption at the Conference of the Parties to the Convention on Biological Diversity in Nagoya in October 2010. However, to be successful, the scientific contribution of botanic gardens needs to be strengthened, as does government policy and commitment. Botanic garden research to underpin conservation action, including the role of botanic garden horticulture, training and international capacity building, has a major part to play and needs to be better understood and better coordinated. We provide examples based on the experience of the Royal Botanic Garden Edinburgh in the UK and overseas. Government policy, at national and international levels, needs to reflect the fundamental importance of plant diversity in maintaining the biosphere and supporting humanity. The commitment of significant new resources is an essential prerequisite for success, but this needs to be well coordinated, inclusive of all stakeholders and carefully targeted. A further challenge is the need to integrate better the plant diversity related activities of what are currently diverse and disconnected sectors, including agriculture, forestry, protected area management and botanic gardens. PMID- 22059249 TI - Plant diversity and conservation in China: planning a strategic bioresource for a sustainable future. AB - China is one of the richest countries for plant diversity with approximately 33 000 vascular plant species, ranking second in the world. However, the plant diversity in China is increasingly threatened, with an estimated 4000-5000 plant species being threatened or on the verge of extinction, making China, proportionally, one of the highest priorities for global plant biodiversity conservation. Coming in the face of the current ecological crisis, it is timely that China has launched China's Strategy for Plant Conservation (CSPC). China has increasingly recognized the importance of plant diversity in efforts to conserve and sustainably use its plant diversity. More than 3000 nature reserves have been established, covering approximately 16% of the land surface of China. These natural reserves play important roles in plant conservation, covering more than 85% of types of terrestrial natural ecosystems, 40% of types of natural wetlands, 20% of native forests and 65% of natural communities of vascular plants. Meanwhile, the flora conserved in botanical gardens is also extensive. A recent survey shows that the 10 largest botanical gardens have living collections of 43 502 taxa, with a total of 24 667 species in ex situ conservation. These provide an important reserve of plant resources for sustainable economic and social development in China. Plant diversity is the basis for bioresources and sustainable utilization. The 21st century is predicted to be an era of bio economy driven by advances of bioscience and biotechnology. Bio-economy may become the fourth economy form after agricultural, industrial, and information and information technology economies, having far-reaching impacts on sustainable development in agriculture, forestry, environmental protection, light industry, food supply and health care and other micro-economy aspects. Thus, a strategic and forward vision for conservation of plant diversity and sustainable use of plant resources in the 21st century is of far-reaching significance for sustainable development of Chinese economy and society. PMID- 22059250 TI - Informing and influencing the interface between biodiversity science and biodiversity policy in South Africa. AB - South Africa, as a megadiverse country (+/-21 700 vascular plants, 4800 vertebrates and 68 900 invertebrates described), is presently engaged with an extended, modified Global Strategy for Plant Conservation (GSPC). The country is fortunate in having a strong tradition of systematics research and, inter alia, houses several million preserved plant specimens (+/-1 million databased and georeferenced), allowing taxonomists and conservationists to track both the occurrence and distribution of indigenous and naturalized plant species. These rich local resources have been extensively drawn upon to deliver, with varying degrees of success, the 16 outcome-oriented GSPC 2010 Targets. The National Environmental Management: Biodiversity Act (NEMBA, 2004), the National Biodiversity Strategy and Action Plan (NBSAP) and the National Biodiversity Framework (NBF) have provided a robust legislative, enabling and policy framework for making operational and advancing GSPC-related efforts. However, within an emerging economy, the conservation of biodiversity has competed for government resources with housing, sanitation, primary education, basic health care and crime prevention, delivery of which translates to the currency of politicians: votes. A key challenge identified by local (and global) biodiversity scientists for the current GSPC phase is broad-scale advocacy, communicating the changing state of nature, and the inter-relatedness of biodiversity and human well-being. The nature of meeting this challenge is explored. PMID- 22059251 TI - How has government policy post-Global Strategy for Plant Conservation impacted on science? The Ethiopian perspective. AB - In this paper, existing relevant Ethiopian government biodiversity-related policies and strategies, and mandates of various institutions prior to GSPC targets, are reviewed. Response to whether or not institutions responded to GSPC targets as the result of new policies or rebranded their work to fit within the context of existing policies and adjust their outcomes to fit into the GSPC targets is provided. The Ethiopian national report of 2009 submitted to the Convention of Biological Diversity Secretariat is reviewed and gaps analysed. The policies of the Federal government (and implementing institutions) post-GSPC so far have had only a limited impact on science, but research institutions have aligned their outputs to fit with the GSPC targets. Suggestions, conclusions and recommendations are made in order to work effectively towards the realization of the GSPC targets beyond 2010 in Ethiopia. PMID- 22059252 TI - Definition and insertion of the GSPC in the political context of Mexico. AB - Mexico as a megadiverse country houses between 6 and 8% of the world's flora. However, the Mexican flora is facing challenges, including the presence of at least 981 threatened plant species and 618 exotic plant species, habitat loss, pollution, overexploitation of natural resources and the adverse effects of climate change, which are compromising its conservation and sustainable use. Mexico has been actively involved in the development and update of the Global Strategy for Plant Conservation (GSPC) adopted by the Convention on Biological Diversity (CBD). As a party to CBD, Mexico has established a Coordinating Committee for the Mexican Strategy for Plant Conservation (MSPC), which has adapted the GSPC to fit national needs and drafted a number of projects, indicators, means of verification and actors to ensure that the MSPC, as a public policy tool, really drives conservation and sustainable use actions among all sectors and lasts beyond the current administration. An agenda is being developed with activities that include the following: approaching Congress, identifying the relevance of the MSPC in the National Development Plan and the Mexican Biodiversity Strategy, making use of current environmental policies and an aggressive awareness programme. The MSPC includes simultaneous programmes of technical and political work. PMID- 22059253 TI - Criminal sittings - rape in the colony, New Zealand, 1862. AB - In 1862 His Honor, Justice Johnston, issued his instructions to the jury of the New Zealand Supreme Court for two simultaneous rape trials - the alleged rape of a European woman by two Maori men, and an alleged "assault with intent to commit a rape" of a Maori woman by a European man. This article argues that those instructions should be read within an historiographical critique of British colonial expansion, print capitalism and violence. Drawing on feminist postcolonial theorizing the question posed here, is, "What is the historical, ideological context for a newspaper reporting of the possible rape of a Maori woman in 1862? PMID- 22059254 TI - Cell phones and brain cancer: should you be worried? Statement linking cell phones to brain tumors causes fear, confusion. PMID- 22059255 TI - New technologies brighten up low vision. PMID- 22059256 TI - Artificial pancreas: outlook is promising. PMID- 22059257 TI - Smoking and prostate cancer. Research suggests that smoking makes prostate cancer worse. PMID- 22059258 TI - Xarelto: a new drug for new joints. Hip and knee recipients can avoid postsurgical clots without undergoing painful injections. PMID- 22059259 TI - I've been diagnosed with chronic prostatitis. What can I do for my frequent nighttime urination? PMID- 22059260 TI - Can the bisphosphonate I'm taking for osteoporosis actually cause a bone fracture? PMID- 22059261 TI - I've tried rattlesnake, frog legs and other exotic foods. Are there any I should avoid? PMID- 22059262 TI - Introduction: educational topics important to medical and graduate students. PMID- 22059263 TI - Questions regarding management of cardiopulmonary arrest. PMID- 22059264 TI - Thoughts on techniques for the removal of cystic and urethral calculi. PMID- 22059265 TI - Comments on transurethral cystoscopy and on clinical practice. PMID- 22059266 TI - Public charity and public piety: the missionary vocation of the daughters of charity as Catholic-reformation missionaries. PMID- 22059267 TI - Swishing on the "boulevards exterieures": representations of male same-sex desire in "fin-de-siecle" popular culture. PMID- 22059268 TI - "The lungs of Paris": urban reform, hygienic strategies, and the politics of parks, 1902-1920. PMID- 22059269 TI - The Paris municipal parks from empire to republic. The political transformation of public space, 1871-1900. PMID- 22059270 TI - The pathology of extravagant behavior. PMID- 22059271 TI - The police and the subculture: same-sex sexuality as crime in Paris in the 1870s. PMID- 22059272 TI - "There are no safe women": prostitution in France during the Great War. PMID- 22059273 TI - "To repress the exuberance of their characters": self-control and the definition of womanhood in nineteenth-century France. PMID- 22059274 TI - Treating illness in the nineteenth century: the work of doctors Itard and Blanchet and the medicalization of the French deaf population. PMID- 22059275 TI - Writing home: French troops, family correspondence, and the First World War. PMID- 22059276 TI - Are Europe's cities better? PMID- 22059277 TI - [Characteristics of urbanization in modern China]. PMID- 22059278 TI - Jung's psychology in the light of his personal myth. PMID- 22059279 TI - [The supervision of psychiatric patients in Poland in the second half of the 18th century]. PMID- 22059280 TI - Medicare program; home health prospective payment system rate update for calendar year 2012. Final rule. AB - This final rule sets forth updates to the home health prospective payment system (HH PPS) rates, including: the national standardized 60-day episode rates; the national per-visit rates; and the low utilization payment amount (LUPA) under the Medicare PPS for home health agencies effective January 1, 2012. This rule applies a 1.4 percent update factor to the episode rates, which reflects a 1 percent reduction applied to the 2.4 percent market basket update factor, as mandated by the Affordable Care Act. This rule also updates the wage index used under the HH PPS, and further reduces home health payments to account for continued nominal growth in case-mix which is unrelated to changes in patient health status. This rule removes two hypertension codes from the HH PPS case-mix system, thereby requiring recalibration of the case-mix weights. In addition, the rule implements two structural changes designed to decrease incentives to upcode and provide unneeded therapy services. Finally, this rule incorporates additional flexibility regarding face-to-face encounters with providers related to home health care. PMID- 22059281 TI - Electronic consultations between primary and specialty care clinicians: early insights. AB - Electronic consultation (e-consultation) is an emerging tool that primary care clinicians can use to communicate with specialists about patients asynchronously- that is, at different times that are convenient for each physician. To conduct an e-consultation, clinicians use either a Web-based program or a shared electronic medical record. Early adopters of e-consultation describe positive experiences for patients, clinicians, and health systems, including improved continuity of care, access to specialists, convenience, and information transfer. E consultation presents opportunities to improve health care quality and reduce specialty care costs, but dissemination will be limited unless incentives are created and clinicians are encouraged to use e-consultation through financial reimbursement. PMID- 22059282 TI - Reconstructive pelvic surgery. PMID- 22059283 TI - Sports medicine. PMID- 22059284 TI - Child neurology. PMID- 22059285 TI - Notice of redundant publication. Nuclear reprogramming in cell-free extracts. PMID- 22059286 TI - Comparison of DNA isolation methods and detection of Salmonella spp. from animal faeces and dust using invA real-time PCR. AB - There is a strong interest to reduce the expenditure for the detection of Salmonella spp. from animal faeces and environmental samples from primary production according to ISO 6579:2002 Annex D by including a rapid and effective method to detect Salmonella spp. already after pre-enrichment in BPW. It has been shown that real-time PCR methods are very effective to detect Salmonella organisms after pre-enrichment of foods. However, materials from primary animal production compose of much higher amounts of substances which might inhibit the sensitivity of real-time PCR. Different techniques of DNA isolation after pre enrichment of artificially inoculated bovine faecal material were used to compare their detection limit and detection probability using an invA 5' nuclease real time PCR approach. A detection probability of 100% was shown at 10(5) cfu/ml using the QIAamp DNA Stool Mini Kit (Qiagen, Germany), at 10(4) cfu/ml using the High Pure PCR Template Preparation Kit (Roche, Germany) and at 10(3) cfu/ml using thermal cell lysis or an in-house lab protocol, respectively. In comparison DNA isolation by thermal cell lysis revealed a very good detection limit, low costs and almost no risks of contamination. Furthermore, caecal contents from pigs were analysed by ISO 6579:2002 Annex D and the invA real-time PCR using thermal cell lysis for DNA extraction. As a result neither false positive nor false negative findings were obtained. Inclusion of the real-time PCR after pre-enrichment of samples in BPW followed by bacterial detection of Salmonella only with samples positive with real-time PCR might be a valuable tool to fulfil the international standard of ISO 6579:2002 Annex D but also to diminish the expenditures. However, it must be stated that the modification of an international standard method and its use in routine diagnostic requires the validation and registration of national and/or international competent authorities. PMID- 22059287 TI - Two outbreaks of virulent systemic feline calicivirus infection in cats in Germany. AB - Over the last years, several outbreaks of virulent systemic feline calicivirus (VS-FCV) infection have been described in the USA and several European countries. The paper describes two outbreaks of VS-FCV infection in cats in Germany. Data concerning clinical, laboratory, and histopathological features ofVS-FCV infection were collected from two outbreaks affecting 55 and 4 cats, respectively. Presence of feline calicivirus was confirmed by PCR followed by sequencing of the PCR-products. Clinical signs were variable, including severe upper respiratory tract infection, dyspnoea, oral and footpad ulceration, facial oedema, enteritis, pneumonia, bleeding disorder, high fever, and icterus. Both outbreaks were characterized by a high mortality rate.The present report describes the first documented outbreaks of VS-FCV infection in cats in Germany. Clinical and histopathological features are comparable to outbreaks described in the USA and Europe. However, phylogenetic analysis of the virus genome suggests that virus strains involved in these outbreaks were different from each other and from virulent strains isolated before, confirming the known genetic variability of FCV. PMID- 22059288 TI - Investigation of serum protein profiles in sheep naturally infected with foot-and mouth disease virus. AB - This study was carried out to determine serum protein profiles in naturally infected sheep with foot-and-mouth disease virus (FMDV). The study material consisted of twelve healthy and 36 sheep with foot-and-mouth disease (FMD). FMD had been diagnosed on the basis of clinical findings and results of serological examination. Serotypes serologically detected in the FMDV-infected sheep were as follows: O (n = 11), A (n = 8) and mixed infection with serotypes O, A and Asia-1 (n = 17).The total protein, albumin and globulin concentrations as well as Albumin/Globulin ratio were slightly different among the groups (P < 0.05). Three protein bands of 66 kDa, 45 kDa and 20 kDa were remarkable. Moderate differences were determined between healthy and infected sheep for proportion of distribution in serum proteins. In conclusion, serum protein concentrations and serum protein profiles were slightly changed and no specific serum protein profile occurred in sheep infected with either O or A or in sheep mixed infected with the O and A and Asia-1 serotypes of FMDV compared to healthy ones. PMID- 22059289 TI - Antimicrobial susceptibility testing of German Campylobacter fetus subsp. venerealis isolates by agar disk diffusion method. AB - Campylobacter fetus subsp. venerealis is the causative agent of bovine genital campylobacteriosis and is transmitted by asymptomatic carrier bulls via contaminated semen during artificial insemination. The aim of the present study was to determine the in vitro susceptibility of Campylobacter fetus subsp. venerealis isolated from bovine specimens in the years from 2000 to 2009 in Germany to antibiotics generally used in semen treatment. The susceptibilities of 50 strains to spectinomycin (10 microg), gentamicin (10 microg), streptomycin (25 microg), penicillin (10 microg), lincomycin (10 microg), ciprofloxacin (5 microg), erythromycin (30 microg) and tetracycline (30 microg) were determined using a disk diffusion susceptibility test. All strains were susceptible to gentamicin. A considerably reduced susceptibility to one or more antimicrobial agents was detected in seven out of 50 isolates (14%) with the most frequent reduction in susceptibility to lincomycin and spectinomycin. Furthermore, strains with reduced susceptibility to more than one antimicrobial agent were always associated with reduced susceptibility to lincomycin. It is recommended to determine the antimicrobial susceptibility of Campylobacter fetus subsp. venerealis isolates in order to evaluate the efficacy of the generally used antibiotic treatment of bull semen and to detect possible resistances. PMID- 22059290 TI - Cloning of equine herpesvirus type 1 438/77 strain genome as a bacterial artificial chromosome. AB - Equine herpesvirus type 1 (EHV-1) is a major cause of respiratory and reproductive diseases in horses worldwide. The genome of EHV-1 strain 438/77 (isolated from an aborted equine fetus) was cloned as a bacterial artificial chromosome (BAC) in E. coli without any gene deletions. The mini-F plasmid sequence was inserted in the middle of ORF19 and 20 via homologous recombination following co-transfection of viral DNA and plasmid pE19_20/HA into RK13 cells. Circular viral DNA was extracted from RK13 cells infected with purified recombinant virus expressing green fluorescent protein (GFP) and electrophorated into E. coli DH10B cells. The clone harboring the BAC was screened and analyzed by PCR and RFLP. Reconstitution of the recombinant virus was achieved successfully by transfection of the BAC DNA into RK13 cells. The mini-F sequence in the reconstituted virus was subsequently removed by homologous recombination between virus DNA and plasmid pE1920XM, inducing a point mutation in the Xbal site in ORF19. Comparison of RFLP profiles of the rescued, recovered and the wild type viral genome demonstrated that no unexpected changes occurred during mutagenesis. In vitro replication assays showed that BAC-reconstituted virus mutant growth kinetics and plaque formation morphology/size were indistinguishable to those measured for wild-type virus. PMID- 22059291 TI - Avian polyomavirus infection of a fledgling budgerigar (Melopsittacus undulatus) and differential diagnoses of viral inclusions in psittacine birds--case report and mini-review. AB - A two-week-old budgerigar (Melopsittacus undulatus) of an outdoor aviary died suddenly and was submitted for determination the cause of illness and death. Macroscopically, the sparsely feathered animal was in a poor body condition. Histopathological examination revealed in various mesenchymal and epithelial tissues, numerous up to 15 microm in diameter large intranuclear, amphophilic to basophilic inclusion bodies with a clearing of the centre. Additionally, a feather dysplasia and retention hyperkeratosis of feather follicles was found. Ultrastructurally, viral particles of approximately 35 nm in diameter were detected in the feather follicle epithelium. A PCR for Avian Polyomavirus on fresh skin samples was negative whereas on formalin-fixed kidney samples with a high amount of viral inclusion bodies yielded a positive result. In addition, viral inclusion body diseases, like Avian Poxvirus, Psittacine Beak and Feather disease virus, Avian Adenovirus, Psittacine Herpesvirus and papillomavirus of psittacines are summarized and compared in the present article. PMID- 22059292 TI - [Outbreak of subclinical mastitis due to beta hemolytic group L streptococci (S. dysgalactiae ssp. equisimilis) in an Austrian dairy herd]. AB - This study is reporting an outbreak of subclinical mastitis due to beta-hemolytic group L streptococci in an Austrian dairy herd with a history of high somatic cell count. At the first survey 16 of 33 lactating cows (28 quarters of 132) were cultured positive for beta-hemolytic, CAMP and esculin negative cocci that grew on Columbia blood agar with small grey catalase negative colonies. With the commercial API 20 Strep system (bioMerieux, F) isolates were classified as members of streptococci group L. All tested strains (eight of 28) produced acid from ribose, lactose, trehalose, amidon and glycogen; they hydrolysed hippurate and showed beta-glucuronidase, beta-galactosidase, alkaline phosphatase, leucinaminopeptidase and arginindehydrolase activity. Isolates were sensitive to bacitracin but resistant to tetracycline. Using phenotypic characterisation as well as sequence analysis of the 16S-23S intergenic spacer region of a representative strain, recovered isolates were identified as Streptococcus (S.) dysgalactiae ssp. equisimilis. Mastitis was characterized by normal milk secretions and absence of clinical abnormalities but high elevations of somatic cell count. Based on the characteristics of the strains and on the observations during the first herd survey, contagious transmission during milking as a result of poor milking hygiene was assumed. The mastitis was controlled through implementation of a strict hygiene protocol including use of single-use udder towels, post milking teat desinfection and cluster disinfection between milking cows in combination with antibiotic treatment of infected udders. PMID- 22059293 TI - A pilot study on ethanol-polyethylene glycol-formalin fixation of farm animal cadavers. AB - Most embalming of cadavers for anatomical dissection in veterinary medicine has used 6-10% formaldehyde resulting in discoloured and rigid specimens. This project produced teaching specimens of sheep, horse and calf cadavers having their musculoskeletal and visceral structures with a natural appearance using a fixation solution with lowered concentrations of formaldehyde (2% and 3%) together with ethanol and polyethylene glycols. Fixation parameters (palpable consistency, flexibility, colour, tissue hydration and odour) were assessed qualitatively by twice weekly dissections over two months for sheep and three months for horses and calf. Formaldehyde levels, measured in the breathing zone, were below the maximum allowable concentration in all specimens except for a 300 kg horse cadaver. To evaluate the effectiveness of the fixation solution in microbial inhibition, tissue samples were taken and analyzed for the presence of culturable aerobic and anaerobic bacteria, yeasts and moulds. Single colonies of Pseudomonas oryzihabitans, Chryseobacterium sp., Acinetobacter sp. were isolated from lungs, and Micrococcus sp. and Bacillus sp. were isolated from one muscle sample. PMID- 22059294 TI - A spatial assessment of Culicoides spp. distribution and bluetongue disease risk areas in Austria. AB - Bluetongue disease (BT) was introduced into Central Europe in the summer of 2006 and has since affected most European countries. In this study we analysed the distribution of the biting midge vector Culicoides spp. in Austria and modelled Bluetongue disease risk zones. Culicoides spp. abundance data was collected from weekly catches of 14 months from 54 trapping locations. The corresponding weather data mean temperature (p < 0.001), wind (p < 0.001), relative humidity (p = 0.019) and altitude (p = 0.059) were identified as predictors on Culicoides spp. distribution in a regression model (R 2.8.0). The majority of catches were detected at temperatures above 10 degrees C and at relative humidities between 65 80%. The point data of these parameters originating from 186 meteorological stations were interpolated using the Geostatistical Analyst Kriging tool (ESRI ArcGIS 9.3). To create seasonal risk maps we overlaid regions with optimal temperature and humidity conditions with domestic ruminants density data. Our results show that the summer season holds the greatest risk of a BT epidemic with 25.9% of the analysed area providing optimal conditions for vector abundance and 12.4% showing contact risk with ruminant hosts. This project (1) provides fundamental data on the Culicoides spp. distribution in Austria, (2) determines limiting climatic parameters on vector abundance and (3) identifies risk areas by including areas of possible host-parasite-interactions. These high-risk areas can subsequently be given special attention for precautionary monitoring and surveillance measures. PMID- 22059295 TI - Analysis of bacterial load and prevalence of mixed infections with Lawsonia intracellularis, Brachyspira hyodysenteriae and/or Brachyspira pilosicoli in German pigs with diarrhoea. AB - Lawsonia (L.) intracellularis, Brachyspira (B.) hyodysenteriae and B. pilosicoli are important pathogens in domestic pig production world-wide, responsible for porcine intestinal adenomatosis, swine dysentery, and porcine intestinal spirochetosis, respectively. Conventional PCR is the major diagnostic tool in the detection of the three pathogens, but the sole detection of bacterial DNA might lead to misinterpretations of results with respect to their clinical relevance, especially with mixed infections. Thus, the present study targeted the detection and quantification of the three pathogens in samples from herds with a case history of diarrhoea. Herds and samples were selected by the practitioners on a voluntary basis. Results were based on 1176 individual samples from 95 herds from Southern Germany. The pathogens were detected simultaneously by multiplex real time PCR. The overall prevalence for L. intracellularis, B. hyodysenteriae and B. pilosicoli was 12.6%, 8.4% and 3.2% in faecal samples and 48.4%, 24.2% and 31.6% in herds, respectively. Sixty one percent, 82.6%, and 73.4% of herds positive for L. intracellularis, B. hyodysenteriae, and B. pilosicoli, respectively, had mixed infections. Median log values of DNA equivalents/g of faeces for L. intracellularis, B. hyodysenteriae and B. pilosicoli were 3.3, 5.9 and 3.2, with maxima of 8.3, 8.0 and 6.3, respectively. Within herd prevalence of B. hyodysenteriae and B. pilosicoli as well as the load of B. hyodysenteriae were significantly associated with the severity of diarrhoea. PMID- 22059296 TI - Presence of porcine parvovirus in sera from pigs is independent of antibody titers. AB - Porcine parvovirus (PPV) is a widespread DNA virus that causes reproductive failure in swine. The aim of the present study was to investigate the presence of PPV in sera of nursery piglets (healthy n = 191 and wasting n = 132) and regularly vaccinated sows (with different parity rank [PR] n = 129), collected from different herds. Altogether, 452 animals were sampled in 27 herds owned by five companies. All sera were analyzed for the presence of PPV DNA by nested-PCR. The samples from sows were in addition tested for the presence of antibodies by Hemagglutination Inhibition (HI). PPV DNA was detected in healthy piglets (15.7%), wasting piglets (18.2%) and sows (17.8%). 25 herds had at least one positive sample and four companies had positive animals. The serology revealed that 84.7% of the sows had detectable antibodies and the fourth PR sows had the highest mean PPV antibody titers. Thirteen sows (19.1%) were found to be positive for DNA detection in the presence of high levels of antibody titers (> 512). This finding indicates that PPV DNA can be detected in different swine production categories irrespective of antibody titers. PMID- 22059297 TI - [Comparison of different applications of the sonographic contrast medium Levovist]. AB - The influence of the application modes (bolus injection, infusion) of the sonographic signal enhancers Levovist was investigated in a total of 24 dogs. The animals in the bolus group were given 0.2 ml/kg body mass Levovist at a concentration of 300 mg/ml while in the other group the same amount was continuously injected over a time of two minutes. Signal enhancement was measured by an audiodoppler. Contrast duration above six, twelve, 18 and 24 dB and maximum signal enhancement were determined for each application mode. The comparison of these parameters showed that a statistically significant longer contrast duration (significance level p less than 0,05) at 0 and 6 dB can be achieved by continuous injection. Bolus application, on the other hand, resulted in significantly higher maximum contrast enhancement. With time consuming investigations (perfusiondiagnostic, shuntdiagnostic) the contrast effect can be partly extended with continuous injection but the technical requirements are higher and there is the risk that the acoustic properties of the microbubbles are negatively influenced. PMID- 22059298 TI - [Influence of exercise on horses' limb volume, measured by an optoelectronic device]. AB - This study tested for the first time an optoelectronic device (Perometer*) measuring limb volume of horses. An analysis of its application was performed regarding the influence of different types of physical exercise on the volume of the extremities. 40 horses were divided into four groups often horses, each group being exposed to exercise, differing in kind and duration of lunging, horse ridden and riderless. The volume measurement was performed by determining the inactive value (I) after a twelfe-hour standing period, the load value (II) immediately after exercise and recovery value (III) one hour after exercise. The results showed a highly significant decrease in limb volume of 5.7% between values (I) and (II), as well as a highly significant increase of 68% between (II) and (III). The volume changes observed in male horses were significantly higher than in female horses. Volume changes in horse-ridden groups were higher than riderless ones, but not significant. There were fewer leg volume changes at low ambient temperatures (1-12 degrees C) compared to high temperatures (23-31 degrees C), but these were not statistically significant. Well-trained horses showed lower volume changes than less trained horses (not statistically significant). The Perometer is a fast and reliable tool for measuring limb volume of horses. The ICC (Interclass Correlation Coefficient) calculated a high measurement reproducibility of 0.996. A variance analysis showed no significant differences between the three repeated leg measurements. Thus, the Perometer can be used for monitoring and quantifying edema and documenting limb volume changes resulting from training, wearing compression stockings or bandages, manual lymph drainage. PMID- 22059299 TI - Learning about faces: effects of trustworthiness on affective evaluation. AB - The results of two studies on the relationship between evaluations of trustworthiness, valence and arousal of faces are reported. In Experiment 1, valence and trustworthiness judgments of faces were positively correlated, while arousal was negatively correlated with both trustworthiness and valence. In Experiment 2, learning about faces based on their emotional expression and the extent to which this learning is influenced by perceived trustworthiness was investigated. Neutral faces of different models differing in trustworthiness were repeatedly associated with happy or with angry expressions and the participants were asked to categorize each neutral face as belonging to a "friend" or to an "enemy" based on these associations. Four pairing conditions were defined in terms of the congruency between trustworthiness level and expression: Trustworthy congruent, trustworthy-incongruent, untrustworthy-congruent and untrustworthy incongruent. Categorization accuracy during the learning phase and face evaluation after learning were measured. During learning, participants learned to categorize with similar efficiency trustworthy and untrustworthy faces as friends or enemies and thus no effects of congruency were found. In the evaluation phase, faces of enemies were rated as more negative and arousing than those of friends, thus showing that learning was effective to change the affective value of the faces. However, faces of untrustworthy models were still judged on average more negative and arousing than those of trustworthy ones. In conclusion, although face trustworthiness did not influence learning of associations between faces and positive or negative social information it did have a significant influence on face evaluation that was manifest even after that learning. PMID- 22059300 TI - Anticipated emotions and personal experience for predicting behavioral intentions and behavioral expectations. AB - We tested how anticipated emotions interact with personal experience in risk behavior to improve predictions from TPB on behavioral intention (BI) and behavioral expectation (BE) for sex without condom (Study 1) and excessive drinking (Study 2). In the moderate-high experience group, anticipated emotional profiles (AEPs) improve TPB prediction from 28% to 45% in the case of BI and from 19% to 40% in that of BE in relation to sexual risk behavior (Study 1), and from 23% to 36% in the case of BI and from 17% to 31% in that of BE in relation to binge drinking (Study 2). However, in the low-experience group (Study 2) AEPs improve TPB predictions for BI (12% to 34%) but not for BE, showing that in less experienced people BI and BE are not equivalent: anticipated emotions have different relevance in their prediction. These results were replicated using a general negative anticipated emotion index (averaging emotional categories). PMID- 22059301 TI - Cost of mental set reconfiguration between digits and their photisms in synaesthesia. AB - In this study we present an experiment investigating the reconfiguration process elicited by the task switching paradigm in synaesthesia. We study the time course of the operations involved in the activation of photisms. In the experimental Group, four digit-color synaesthetes alternated between an odd-even task and a color task (to indicate the photism elicited by each digit). In both tasks, the target stimuli were numbers between 1 and 9 written in white. One of the control groups ran the same tasks but this time with colored numbers (Naive Control Group). The results of these studies showed the expected pattern for the control group in the case of regular shift: a significant task switch cost with an abrupt offset and a cost reduction in long RSI. However for the experimental group, we found switch cost asymmetry in the short RSI and non-significant cost in the long RSI. A second control group performed exactly the same tasks as the experimental group (with white numbers as targets and a second imaginary color task) -Trained Control Group-. We found no cost for this second control group. This means that the cost of mental set reconfiguration between numbers (inducers) and their photisms (concurrent sensations) occurs, that there is a specific cost asymmetry (from photisms to inducers) and that this cost cannot be explained by associative learning. The results are discussed in terms of exogenous and endogenous components of mental set reconfiguration. PMID- 22059302 TI - Interference in visual perception by verbal and spatial cognitive activity. AB - In two experiments we tested the hypothesis that cognitive processing based on spatial imagery produces more deterioration of visual perception than cognitive processing based on verbal codes. So, we studied the effect on visual perception of two cognitive tasks, one of spatial imagery and the other a verbal task. In the first one, with 30 participants, we analyzed the mental load and ocular behaviors in both cognitive tasks. In the second experiment, with 29 participants, we studied the effect of both tasks on a visual search task, using a dual-task experimental paradigm. The verbal task presented higher mental load than the imagery task when both tasks were carried out with visual search task, and there was more deterioration in stimulus detection with the verbal task. We can conclude that: (1) cognitive tasks produce important deterioration in the capacities of visual search and identification of stimuli; (2) this deterioration has two components: (a) an inefficient search, associated with alterations of the gaze patterns while performing cognitive tasks, and (b) a general interference, nonspecific to spatial codes, in the process of identification of looked-at stimuli; (3) this cognitive interference is related to the mental load or effort required by the cognitive task. PMID- 22059303 TI - The semantics of 'unless' conditionals: evidence from 'unless' and disjunctive inferences. AB - We report the results of an experiment investigating conditional inferences from conditional assertions such as 'Juan won't go to Leon unless Nuria goes to Madrid' and 'Either Nuria goes to Madrid or Juan won't go to Leon'. This experiment addresses Dancygier's claims about the semantics of 'unless' by examining inferential endorsements of 'not-A unless B' and 'Either B or not-A' in the canonical order, presenting the categorical premise after the conditional assertions, and in the inverse order, presenting the categorical premise before the conditional assertions. The results of the experiment confirm that the representation of 'unless' includes two possibilities, although as Dancygier holds one of the possibilities may not be complete. The implications of the results are discussed in the context of the strategic nature of conditional reasoning and recent convergent theories of linguistic processing. PMID- 22059304 TI - Inhibitory processes, working memory, phonological awareness, naming speed, and early arithmetic achievement. AB - This study identified the cognitive processes that underlie the individual differences in early mathematical performance in elementary school children. Taking into account the Baddeley framework multicomponent model, the inhibitory processes, working memory, phonological awareness, and naming speed are considered to be related to early math learning. To examine this relationship, we compared the performance of a total of 424 typically developing middle-class children, aged between 4 and 7 years in a battery of cognitive and early numeric tests: The Utrecht Early Numeracy Test, the Rapid Automatized Naming Test, Spanish version of the Stroop task, the Numeracy Interference Test, Digit Span test, and Phonological Knowledge Test. The mean age of the participants was 72.21 months (sd = 14.8), and 48.6% were male and 51.4% were female. The results demonstrated that children performing worst on central executive, phonological processing, and inhibitory processes showed lower results in early mathematical tasks measured by The Utrecht Early Numeracy Test. Results supported the notion that the executive system is an important predictor of children's mathematical performance. PMID- 22059305 TI - Semantic priming effects in a lexical decision task: comparing third graders and college students in two different stimulus onset asynchronies. AB - Differences in the semantic priming effect comparing child and adult performance have been found by some studies. However, these differences are not well established, mostly because of the variety of methods used by researchers around the world. One of the main issues concerns the absence of semantic priming effects on children at stimulus onset asynchrony (SOA) smaller than 300ms. The aim of this study was to compare the semantic priming effect between third graders and college students at two different SOAs: 250ms and 500ms. Participants performed lexical decisions to targets which were preceded by semantic related or unrelated primes. Semantic priming effects were found at both SOAs in the third graders' group and in college students. Despite the fact that there was no difference between groups in the magnitude of semantic priming effects when SOA was 250ms, at the 500ms SOA their magnitude was bigger in children, corroborating previous studies. Hypotheses which could explain the presence of semantic priming effects in children's performance when SOA was 250ms are discussed, as well as hypotheses for the larger magnitude of semantic priming effects in children when SOA was 500ms. PMID- 22059306 TI - Thermal sensitivity and cardiovascular reactivity to stress in healthy males. AB - This paper examines the association of cardiovascular reactivity with thermal thresholds (detection and unpleasantness). Heart period (HP), systolic (SBP) and diastolic (DBP) blood pressure of 42 health young males were recorded during a cardiovascular reactivity task (a videogame based upon Sidman's avoidance paradigm). Thermal sensitivity, assessing detection and unpleasantness thresholds with radiant heat in the forearm was also estimated for participants. Participants with differential scores in the cardiovascular variables from base line to task > or = P65 were considered as reactors and those how have differential scores < or = P35 were considered as non-reactors. Significant differences were observed between groups in the unpleasantness thresholds in blood pressure (BP) but not in HP. Reactors exhibited significant higher unpleasantness thresholds than non-reactors. No significant differences were obtained in detection thresholds between groups. PMID- 22059307 TI - Effects of a play program on creative thinking of preschool children. AB - The purpose of this study was to evaluate the effects of a play program in the creative thinking of preschool children. The study used a repeated measures experimental pretest-posttest design with control groups. The sample included 86 participants aged 5 to 6 years (53 experimental and 33 control participants). Before and after administering the program, two evaluation instruments were applied: The Torrance Test of Creative Thinking (Torrance, 1990) and Behaviors and Traits of Creative Personality Scale (Garaigordobil & Berrueco, 2007). The program consisted of a weekly 75-minute play session throughout the school year. ANOVA results showed that the program significantly increased the verbal creativity (fluency, flexibility, originality), graphic creativity (elaboration, fluency, originality), and behaviors and traits of creative personality. In the pretest phase, there were no differences in the creativity of boys and girls, and the program stimulated a similar level of change in both sexes. The discussion focuses on the importance of implementing creative programs with preschool children. PMID- 22059308 TI - Functions of the pointing gesture in mothers and their 12 to 36-month-old children during everyday activities. AB - This study longitudinally examined the production of pointing in four Spanish 1 year-old and four Spanish 2-year-old children in interactive situations with their mothers at home over the course of one year. Three aspects were analyzed: a) the functions of the pointing gesture, their accurate comprehension by the interlocutor (mother or child), and their order of emergence in the child; b) whether or not there were differences in the production of pointing according to who initiated the interaction; and c) whether maternal and child speech were related to maternal and child pointing production. The results showed that the pointing function of showing is the most frequent for both children and mothers from groups 1 and 2, and the first to emerge followed by the informing, requesting object, requesting action, and requesting cooperation functions. The accuracy with which these intentions were comprehended was found to be very high for both mother and child. Pointing production was greater when the speaker initiated the interaction than when the other person did, indicating that gestures follow the turn-taking system. Finally, the production of pointing to showing in children and mothers was found to be related to maternal and child speech, while pointing to request cooperation triggered the process of joint activity between mother and child. PMID- 22059309 TI - Infant-mother attachment can be improved through group intervention: a preliminary evaluation in Spain in a non-randomized controlled trial. AB - The quality of infant-mother attachment has been linked to competence in different domains of child development. Research indicates that early intervention can enhance the quality of infant-mother attachment, though its efficacy in a group format has yet to be evaluated. The current study is aimed at examining the usefulness of a group intervention in enhancing infant-mother attachment. An intervention aimed at addressing aspects such as maternal responsivity, sensitivity and childrearing behaviour was developed by the researchers and experienced psychologists. The intervention spanned a period of 14 months starting from the third quarter of pregnancy. The intervention was evaluated among 24 mothers from the Basque region of Spain. The sample consisted of children of both genders in a similar proportion: 45.8% were boys and 54.2% were girls. The children in this sample were full-term born and did not present symptoms of any serious pre- or postnatal complications. The intervention had a statistically non-significant medium effect. Infants whose mothers had received the intervention showed higher rates of secure attachment compared to children from the control group, as assessed by the Strange Situation observation procedure. A potentially significant confounding variable, maternal attachment, was balanced across the intervention and comparison groups. We can tentatively point out that a group intervention may enhance the quality of infant-mother attachment. Nevertheless, because the study design was not randomized, the results of this study remain preliminary and need replication in a full randomized controlled trial designed study. PMID- 22059310 TI - Father involvement and marital relationship during transition to parenthood: differences between dual and single-earner families. AB - Research into the process of becoming mother or father shows very conclusively that this important life transition is accompanied by both a decrease in marital quality and a more traditional division of labour. In this paper these changes are analyzed with special emphasis on the relationships between them and exploring the role played in this process by the mother's work status. Results showed a significant link between the development of marital quality and violated expectations regarding father involvement on childrearing. Dual-earner families were characterized by a specific pattern of changes, with greater stability than single-earner families in marital and parental roles during transition to parenthood and a significant role played by spouse support as a partner, but not as a parent. PMID- 22059311 TI - A confirmatory factor analysis of the "Autoconcepto Forma 5" questionnaire in young adults from Spain and Chile. AB - The aim of this work is to examine the pentafactorial validity of the AF5 Self Concept Questionnaire in Spanish and Chilean young adults. From the responses of a total of 4,383 young adults aged 17 to 22 years (1,918 Spanish, 44%, and 2,465 Chilean, 56%) it was analyzed the reliability of the instrument, the compared validity of the 5 oblique factor model proposed by the authors versus the unifactorial and the orthogonal alternative models, and was studied the invariance of one Chilean sample. The results of confirmatory factor analyses supported the authors' pentafactorial model. The multi-group factorial invariance showed that Chilean sample of the AF5 does not change neither the Spanish factor weights, nor the variances and covariances of the factors, or the error variances of items. Finally, the internal consistency of the five scales was good in the samples of both countries. PMID- 22059312 TI - The five and seven factors personality models: differences and similitude between the TCI-R, NEO-FFI-R and ZKPQ-50-CC. AB - The present study tests the relationships between the three frequently used personality models evaluated by the Temperament Character Inventory-Revised (TCI R), Neuroticism Extraversion Openness Five Factor Inventory - Revised (NEO-FFI-R) and Zuckerman-Kuhlman Personality Questionnaire-50- Cross-Cultural (ZKPQ-50-CC). The results were obtained with a sample of 928 volunteer subjects from the general population aged between 17 and 28 years old. Frequency distributions and alpha reliabilities with the three instruments were acceptable. Correlational and factorial analyses showed that several scales in the three instruments share an appreciable amount of common variance. Five factors emerged from principal components analysis. The first factor was integrated by A (Agreeableness), Co (Cooperativeness) and Agg-Host (Aggressiveness-Hostility), with secondary loadings in C (Conscientiousness) and SD (Self-directiveness) from other factors. The second factor was composed by N (Neuroticism), N-Anx (Neuroticism-Anxiety), HA (Harm Avoidance) and SD (Self-directiveness). The third factor was integrated by Sy (Sociability), E (Extraversion), RD (Reward Dependence), ImpSS (Impulsive Sensation Seeking) and NS (novelty Seeking). The fourth factor was integrated by Ps (Persistence), Act (Activity), and C, whereas the fifth and last factor was composed by O (Openness) and ST (Self- Transcendence). Confirmatory factor analyses indicate that the scales in each model are highly interrelated and define the specified latent dimension well. Similarities and differences between these three instruments are further discussed. PMID- 22059313 TI - Personality and job stress: a comparison of direct effects on parenting. AB - The impact of personality and job characteristics on parental rearing styles was compared in 353 employees. Hypotheses concerning the relationships between personality and job variables were formulated in accordance with findings in past research and the Belsky's model (1984). Structural equation nested models showed that Aggression-hostility, Sociability and job Demand were predictive of Rejection and Emotional Warmth parenting styles, providing support for some of the hypothesized relationships. The findings suggest a well-balanced association of personality variables with both parenting styles: Aggression-Hostility was positively related to Rejection and negatively to Emotional Warmth, whereas Sociability was positively related to Emotional Warmth and negatively related to Rejection. Personality dimensions explained a higher amount of variance in observed parenting styles. However, a model that considered both, personality and job dimensions as antecedent variables of parenting was the best representation of observed data, as both systems play a role in the prediction of parenting behavior. PMID- 22059314 TI - Dynamics of the general factor of personality in response to a single dose of caffeine. AB - General Factor of Personality (GFP) research is an emergent field in personality research. This paper uses a theoretical mathematical model to predict the short term effects of a dose of a stimulant drug on GFP and reports the results of an experiment showing how caffeine achieves this. This study considers the General Factor of Personality Questionnaire (GFPQ) a good psychometric approach to assess GFP. The GFP dynamic mechanism of change is based on the Unique Trait Personality Theory (UTPT). This theory proposes the existence of GFP which occupies the apex of the hierarchy of personality, and extends from an impulsiveness-and aggressiveness pole (approach tendency) to an anxiety-and-introversion pole (avoidance tendency). An experiment with 25 volunteers was performed. All the participants completed the GFPQ and the Sensation-Seeking Scale list of adjectives from the trait version of MAACL-R (Multiple Affect Adjective Checklist Revised) on an empty stomach. The participants in the experimental group (20) received 330 mg of caffeine. All the participants filled in a state version form with the sensation-seeking adjectives every 4.5 minutes. This study considers that the Sensation-Seeking Scale list of adjectives from the MAACL-R, available in both trait and state versions, is a good psychometric approach to assess GFP. The results show that GFP is modified by a single dose of caffeine in the direction predicted by the UTPT. PMID- 22059315 TI - Personality patterns of suicide attempters: gender differences in Ukraine. AB - In the present study, an attempt has been made to investigate the complete 'pattern' of a suicide attempter (SA) within the set of Big Five traits. Two models were used: M1, which includes the five main dimensions of Big Five in the analysis; and M2, which includes facets of those dimensions which were identified as important in M1. The study consisted of a group of SA (men - 326, women - 299) and a group of healthy volunteers (HV) (men - 143, women - 190) with a similar age range. Discriminant analysis (DA) showed that the factors most significant in discriminating the personality pattern of a male SA are (in decreasing order): (E) Extraversion, (N) Neuroticism, (C) Conscientiousness and (O) Openness; and for a female SA these factors were (E) Extraversion, (C) Conscientiousness and (A) Agreeableness. In M2 for men, the largest contribution to pattern recognition is (N3) Depression. Moreover, in M2 for men significant characteristics were (in descending order): (E6) Positive Emotions, (O1) Fantasy, (E4) Activity, and also (N2) Angry Hostility, (C3) Dutifulness, (C4) Achievement Striving, (C2) Order and (O6) Values; and for women: (E4) Activity, (C6) Deliberation, (C2) Order, (A6) Tender-Mindedness, (E5) Excitement Seeking, (E6) Positive Emotions, (C4) Achievement Striving, (A2) Straightforwardness, (C5) Self-Discipline and (E1) Warmth. Analysis of the obtained data demonstrates that suicide attempts amongst males, can largely be associated with personality variables reflecting negative emotions; while female suicide attempts are primarily associated with variables regarding activity and self-regulation. PMID- 22059316 TI - Risk profiles and peer violence in the context of school and leisure time. AB - Though violence at school is by no means a new phenomenon, there has been growing social and scientific concern about this issue in recent years. The present study builds on prior analysis of the roles adolescents play in peer harassment, and the relationship between violence occurring at school and during free time. A representative sample of students between the ages of 14 and 18 was selected in the Community of Madrid (N = 1622) through random cluster sampling (school was the unit of analysis). Participants completed the C.E.V.E.O. questionnaire, which presents fifteen situations involving peer violence. The results reveal a relationship between violent situations occurring at school and during free time, and between the roles of aggressor and victim during free time. A profile analysis yielded three different categories: the "minimal violence exposure" type (1126 adolescents), the "psychological violence exposure" type (413 adolescents), and the "high risk of violence" type (83 adolescents). Judging from these results, we posit that interventions must be designed which tailor to each group and their respective risk situations. PMID- 22059317 TI - Eating habits, physical activity, consumption of substances and eating disorders in adolescents. AB - The aim of this study was to evaluate the differences between adolescents with a high or low risk of developing an eating disorder (ED) in different health behaviors (eating habits, physical activity and the consumption of substances) per gender. The EAT-40 and the Inventory of Behavioral Health in Scholars were applied to 2142 middle school students from Alicante (Spain), of whom 52.8% were girls and 47.2% were boys, with an average age of 13.92 years old (Sd = 1.34). Results indicated that girls with a high risk of developing an ED consumed fewer meals, ate fewer unhealthy foods, followed more diets and paid more attention to nutritional components. Furthermore, they also performed more physical activity with the objective of losing weight, and consumed more tobacco, alcohol and medicines. Boys at high risk of developing an ED followed more diets and paid more attention to nutritional components. For boys, no more differences were found. These results suggest that any program directed at the prevention of ED should not only include nutritional education, but should also seek to promote regular physical activity with objectives other than weight loss or the burning of calories. PMID- 22059318 TI - Drug awareness in adolescents attending a mental health service: analysis of longitudinal data. AB - One of the procedures used most recently with longitudinal data is linear mixed models. In the context of health research the increasing number of studies that now use these models bears witness to the growing interest in this type of analysis. This paper describes the application of linear mixed models to a longitudinal study of a sample of Spanish adolescents attending a mental health service, the aim being to investigate their knowledge about the consumption of alcohol and other drugs. More specifically, the main objective was to compare the efficacy of a motivational interviewing programme with a standard approach to drug awareness. The models used to analyse the overall indicator of drug awareness were as follows: (a) unconditional linear growth curve model; (b) growth model with subject-associated variables; and (c) individual curve model with predictive variables. The results showed that awareness increased over time and that the variable 'schooling years' explained part of the between-subjects variation. The effect of motivational interviewing was also significant. PMID- 22059319 TI - The classification of Spanish adolescents based on substance consumption patterns and the analysis of the relationships within their social developmental contexts. AB - This research is part of the 2006 edition of the Health Behavior in School-aged Children (HBSC) study. The data presented were composed of a sample of 15942 Spanish adolescents ranging from 13 to 18 years of age. The instruments used included a variety of questions related to substance consumption among adolescents, their bio-psycho-social adjustment and developmental contexts, all of which are part of the HBSC study instrument bank. Through classification analysis, as well as significance and effect size tests, we obtained relevant information about the current epidemiology of substance consumption among Spanish adolescents. These results are representative of the Spanish adolescent population which allows the typical risk profile attributed to young people to be clarified. A gradual adjustment can be seen in terms of substance consumption levels in youth and that same level in their friends. Likewise, the analysis of the developmental context (family, friends and school) provides important information when it comes to preventing substance consumption, thus showing the advantages that coherence and connection have between the different environments where youth live, grow up and develop. PMID- 22059320 TI - Psychosocial correlates of condom use and their relationship with worry about STI and HIV in native and immigrant adolescents in Spain. AB - The goal of this study was to analyze how worry about sexually-transmitted infections (STI) and HIV influences attitudes and self-efficacy towards condom use, HIV-related knowledge, HIV-perceived susceptibility and HIV-misconceptions in a multicultural sample in Spain. The sample was composed of 3,051 adolescents aged between 14 and 19 years old who lived in Spain. Of these, 67.7% were native Spaniards and the remaining 32.3% were Latin American immigrants. Results showed that worry about STI and HIV has a direct influence on condom use self-efficacy and HIV-knowledge and HIV-perceived susceptibility. Native Spanish adolescents showed higher positive attitudes towards condom use, greater HIV-knowledge and HIV-perceived susceptibility, and lower negative attitudes towards condoms use and HIV-misconceptions than Latin American adolescents. In the discussion, the importance of worry about STI and HIV is highlighted as a mediator variable that can predict risky sexual behavior and is related to cultural origin. PMID- 22059321 TI - Hand gestures and perceived influence in small group interaction. AB - A laboratory study was carried out to establish the relative importance of verbal and gestural behavior, as well as their interaction, for perceived social influence in more or less competitive small groups. Forty women (psychology students) participated in leaderless small group discussions of different sizes (four-member and eight-member): at the end, each member rated the perceived influence in decision-making of every other member. Verbal dominance coding is based on traditional quantitative conversational dominance (number of talk turns). Gestural coding (conversational, ideational, object-adaptor, self-adaptor gestures) is based on classical gesture classifications. Beside a substantial effect of verbal dominance, the main result is that frequency of object-adaptors and conversational (only in large groups) and ideational (in both small and large groups) gestures increases perceived influence scores particularly when the verbal dominance of the speaker is low. PMID- 22059322 TI - I control therefore I am: effects of mortality salience on control attributions. AB - Terror Management Theory posits that when individuals are faced with their own mortality, they use several defense mechanisms to reduce the existential anxiety caused by the thought of their own death. In this paper, we examined one such mechanism: Control attributions. To do so, we ran an experiment (n = 140) in which we manipulated mortality salience and type of failure (relevant vs. irrelevant consequences) with which participants were faced. Participants were then instructed to evaluate the possible causes of their failure. The results indicated that participants assigned to the mortality salience condition, compared to those assigned to the control group, were more prone to making controllable attributions. That is, even in situations in which individuals are motivated to avoid responsibility (i.e., a relevant failure), mortality salience increased perceived controllability. These results suggest that attributions might serve as a control mechanism to compensate for the sheer uncontrollability of death. PMID- 22059323 TI - Predicting team output using indices at group level. AB - The present study explores the usefulness of dyadic quantification of group characteristics to predict team work performance. After reviewing the literature regarding team member characteristics predicting group performance, percentages of explained variance between 3% and 18% were found. These studies have followed an individualistic approach to measure group characteristics (e. g., mean and variance), based on aggregation. The aim of the present work was testing whether by means of dyadic measures group output prediction percentage could be increased. The basis of dyadic measures is data obtained from an interdependent pairs of individuals. Specifically, the present research was intended to develop a new dyadic index to measure personality dissimilarity in groups and to explore whether dyadic measurements allow improving groups' outcome predictions compared to individualistic methods. By means of linear regression, 49.5 % of group performance variance was explained using the skew-symmetry and the proposed dissimilarity index in personality as predictors. These results support the usefulness of the dyadic approach for predicting group outcomes. PMID- 22059324 TI - Effective behaviors to de-escalate organizational conflicts in the process of escalation. AB - The goal of the present study was to determine what behaviors negotiators can use to help to quell an escalating conflict. In doing so, we formed a sample of professionals who took on the role of negotiator when we provoked an organizational conflict between a superior and subordinate that escalates due to the intervention of research confederates. Trained judges analyzed the negotiators' behaviors that most effectively mitigated the intensity of the conflict in which they were involved. The results demonstrate that the behaviors most effective at de-escalating an escalating conflict are problem-solving and accommodation, especially when said conflict has escalated considerably. Similarly, jointly employing problem-solving and direct fighting behaviors also seems to help de-escalate conflict. The results do not, however, consistently support using a forceful behavioral strategy to de-escalate a conflict in the early stages of escalation. PMID- 22059325 TI - Assessing the impact of dispositional resistance to change on organizational attraction. AB - In recent years there has been an increasing interest among researchers and practitioners to analyze what makes a firm attractive in the eyes of university students, and if individual differences such as personality traits have an impact on this general affect towards a particular organization. The main goal of the present research is to demonstrate that a recently conceptualized narrow trait of personality named dispositional resistance to change (RTC), that is, the inherent tendency of individuals to avoid and oppose changes (Oreg, 2003), can predict organizational attraction of university students to firms that are perceived as innovative or conservative. Three complementary studies were carried out using a total sample of 443 college students from Mexico. In addition to validating the hypotheses, our findings suggest that as the formation of the images of organizations in students' minds is done through social cognitions, simple stimuli such as physical artifacts, when used in an isolated manner, do not have a significant impact on organizational attraction. PMID- 22059326 TI - Exploring the role of national culture on knowledge practices: a comparison between Spain and the UK. AB - In the context of a competitive knowledge-based economy, the knowledge provided by a firm's founders is one of the most important measures of success. This paper aims to identify the role of national culture on a founder's knowledge practices in a modern organisation. Using data collected from 258 Small to Medium sized Enterprises (SME(S)) in the Spanish and UK telecommunication industries (130 from Spain and 128 from the UK), we propose three knowledge management practices to be analysed; namely transfer, transformation and open-mindedness. This paper provides evidence that while Spanish SME(S) are more positively associated with higher levels of transfer and transformation of knowledge, UK SME(S) are more positively associated with higher levels of open-mindedness. Hence, this study serves as an important contribution to the small amount of literature currently available in this field by examining different practices that can be explained by the cultural characteristics of both countries. PMID- 22059327 TI - Consequences of job insecurity and the moderator role of occupational group. AB - In recent decades, transformations in organizations and the labour market have produced an increase in employee job insecurity. In response to this situation, workers present different negative reactions. However, the intensity of these reactions varies across studies that have investigated the outcomes of job insecurity. One possible explanation for this inconsistency may lie in the influence of other factors, such as the occupational group (Sverke et al., 2002). The aim of this study is to provide additional evidence about the relationship between job insecurity and its outcomes (i.e., life satisfaction, job satisfaction, perceived performance and organizational commitment), and examine the moderator role of occupational group in this relationship. The sample was composed of 321 employees from different Spanish organizations. The results showed that job insecurity was directly and negatively related to life satisfaction, job satisfaction and organizational commitment, and they suggest that occupational group moderated relations between job insecurity and three studied outcomes. In the case of life satisfaction and perceived performance, this relationship was stronger among blue collar workers. The relationship between job insecurity and job satisfaction was stronger in white collar workers. The implications and limitations of this study are discussed. PMID- 22059328 TI - The contribution of social rank and attachment theory to depression in a non clinical sample of adolescents. AB - This study explores the relative contribution of the overall quality of attachment to the mother, to the father and to peers (Inventory of Parent and Peer Attachment scales), the style of attachment towards peers (Attachment Questionnaire for Children scale), the social rank variables (submissive behavior and social comparison), and sex and age variables in predicting the depression score (Center of Epidemiological Studies Depression Scale) on a non-psychiatric sample of 13-18 year old adolescents (n = 225). Results of our integrated model (adjusted R-Square of .50) show that attachment variables (overall quality of attachment to the father and to the mother), social rank variables (social comparison and submissive behavior), age and sex are important in predicting depressive symptoms during adolescence. Moreover, the attachment to peers variables (quality of attachment to peers, secure and ambivalent style of attachment) and sex are mediated by the social rank variables (social comparison and submissive behavior). PMID- 22059329 TI - Latin-American immigrant women and mental health: differences according to their rural or urban origin. AB - Spain is one of the EU countries that receive most immigrants, especially from Latin America. The process of migration implies a high level of stress what may have repercussions for the mental health of immigrants. The purposes of this study were: (a) to determine whether the degree of mental health of immigrant women differs according to their rural or urban origin, (b) to compare the mental health of immigrant women with that of the female normative sample of host population (Spain). A sample of 186 Latin American immigrant women (142 from urban areas and 44 from rural areas) was recruited in Barcelona by means of a consecutive case method. A structured interview and the SCL-90-R were administered. The results indicated that the immigrant women from rural origin reported higher levels of psychological symptomatology than those from urban areas. Immigrants reported higher levels of psychological symptomatology than the native female population and in most of the psychological symptoms exceeded 90% of the native Spanish population. Migration is a powerful stressor which may lead to psychological distress. Being female of rural origin and being in an illegal situation is related with an increase in symptomatology. PMID- 22059330 TI - High and low trait anger, and the recognition of anger problems. AB - This study compared three groups of people: (a) high trait anger individuals who recognized personal anger problems (HR); (b) high trait anger individuals who did not recognize personal anger problems (HNR); and (c) low trait anger individuals not reporting personal anger problems (LNR). Compared to LNR participants, HR and HNR groups reported more anger-out (i.e., outward negative expression of anger such as arguing with others), anger-in (i.e., anger suppression and harboring grudges), greater desire to use and actual use of physically aggressive anger expression (e.g., pushing or shoving someone), and less anger control-in (i.e., emotionally focused strategies to lower anger such as relaxation) and anger control-out (i.e., behaviorally focused strategies such as being patient with others). HR individuals reported more trait anger (i.e., higher propensity to experience anger) and less anger control-out than the HNR group. Gender did not relate to the recognition of anger problems. Findings were discussed with regard to theory and clinical implications. PMID- 22059331 TI - Assessment of executive functions in a Brazilian sample of bipolar subjects. AB - Research has demonstrated impairments in executive functions in Bipolar Mood Disorder patients. Evidence shows that this impairment is present in both periods of active symptoms of the disorder, as well as euthymic stages, and is compounded by mood episodes, especially manic phases. The purpose of this study was to compare the executive performance of a sample of Brazilian bipolar patients in depressive episodes, (44 participants), euthymia (37 participants), and in controls (43 participants). The main instrument for evaluation was the Wisconsin Card Sorting Test. Significant differences were found in performance on the Wisconsin Card Sorting Test between Bipolar subjects (Type I) (both in depression and euthymia) and the controls. No significant correlations were found between the number of manic episodes and the performance on execute measurement variables. The findings suggest that the executive dysfunctions in Bipolar Disorder may be related to both transitory and permanent deficits. PMID- 22059332 TI - The contingent negative variation laterality and dynamics in antisaccade task in normal and unmedicated schizophrenic subjects. AB - Contingent negative variation (CNV) topography, hemispheric asymmetry and time course were investigated in healthy subjects and non-medicated paranoid schizophrenic patients in two antisaccade paradigms with the short (800-1000 ms) and long (1200-1400 ms) durations of the fixation period. EEG and electrooculogram (EOG) were recorded. Saccade characteristics and mean amplitudes of slow cortical potentials time-locked to peripheral target were analyzed in 23 healthy volunteers and 19 schizophrenic patients. Compared to healthy control subjects, schizophrenic patients had significantly slower antisaccades and committed significantly more erroneous saccades in the both antisaccade tasks. The prolongation of the fixation period resulted in noticeable decrease of error percent in patients group. The analysis of CNV time-course has revealed two distinct stages in both groups. The early CNV stage was represented by a negative wave with the maximal amplitude over midline fronto-central area, and the late stage was characterized by increased CNV amplitude at the midline and left parietal electrode sites. In healthy subjects the simultaneous activation of frontal and parietal areas was observed in the paradigm with the shorter fixation interval; the increase of the fixation period produced consecutive activation of these areas. Schizophrenic patients' CNV amplitude was generally smaller than that of healthy subjects. The most pronounced between-group differences of the negative shift amplitude were revealed at frontal electrode sites during the early CNV stage in both modifications of the antisaccade task. The deficit of frontal activation revealed in patients at the early stage of antisaccade preparatory set in both antisaccadic paradigms may be related to pathogenesis of paranoid schizophrenia. PMID- 22059333 TI - Perceptions of breastfeeding in mothers of babies born preterm in comparison to mothers of full-term babies. AB - The purpose of the present study was: a) to describe the theme of verbalizations about breastfeeding in mothers' pre-term (M-PT) and full-term (M-FT) infants; b) to examine the association between these themes and mother's anxiety and depression indicators and socio-demographic characteristics and, neonatal characteristics of the infants. The sample consisted of 50 M-PT and 25 M-FT. The mothers were assessed through State-Trait Anxiety Inventory and Beck Depression Inventory and were interviewed using a Guide focusing breastfeeding issues. The M PT group had significantly more mothers with clinical symptom of anxiety than the M-FT group. The M-PT reported more uncertainties and worries about breastfeeding and figured out more obstacles for the successful breastfeeding than the M-FT. These reports were associated positively with the infants' risk neonatal status; lower birth-weight, higher neonatal clinical risk, and more length time stay in NICU were associated with more mothers' worries and seeing obstacles for breastfeeding. In conclusion, the strategies to enhance the breastfeeding rate in the preterm population have to take into account the mothers' psychological status and their ideas in addition to offering information about the advantages of breastfeeding for child development. PMID- 22059334 TI - Objective assessment of gender roles: Gender Roles Test (GRT-36). AB - This study was designed to develop a computerized test to assess gender roles. This test is presented as a decision-making task to mask its purpose. Each item displays a picture representing an activity and a brief sentence that describes it. Participants have to choose the most suitable sex to perform each activity: man or woman. The test (Gender Roles Test, GRT-36) consists of 36 items/activities. The program registers both the choices made and their response times (RTs). Responses are considered as stereotyped when the chosen sex fits stereotyped roles and non-stereotyped when the chosen sex does not fit stereotyped roles. Individual means (RTs) were computed for stereotyped and non stereotyped responses, differentiating between domestic and work spheres. A "D" score, reflecting the strength of association between activities and sex, was calculated for each sphere and sex. The study incorporated 78 participants (69% women and 31% men) ranging from 19 to 59 years old. The results show that: (a) reading speed does not explain the variability in the RTs; (b) RTs show good internal consistency; (c) RTs are shorter for stereotyped than for neutral stimuli; (d) RTs are shorter for stereotyped than for non-stereotyped responses. Intended goals are supported by obtained results. Scores provided by the task facilitate both group and individual detailed analysis of gender role, differentiating the gender role assigned to men from that assigned to women, at the domestic and work spheres. Obtained data fall within the scope of the genderology and their implications are discussed. PMID- 22059335 TI - Spanish validation of the Acceptance of Modern Myths about Sexual Aggression scale (AMMSA). AB - Two studies were conducted with college students to validate the Spanish-language version of the "Acceptance of Modern Myths about Sexual Aggression" scale (AMMSA) (Gerger, Kley, Bohner & Siebler, 2007). This scale assesses modern myths about sexual aggression in a subtle way. In Study 1, 305 students completed the Spanish AMMSA and other scales with related content. In Study 2, 263 participants completed the Spanish AMMSA and answered questions about a hypothetical sexual assault perpetrated by a young man against a female acquaintance. The Spanish AMMSA showed high internal consistency and adequate evidence of validity in both studies. Compared to traditional scales of rape myth acceptance, mean scores on the AMMSA were higher and their distributions more closely approximated normality. These findings suggest that the Spanish version of the AMMSA scale is a useful instrument to study the social perception of sexual aggression. PMID- 22059336 TI - Spanish validation of the Affective Neuroscience Personality Scales. AB - The Affective Neuroscience Personality Scales have been designed to provide a personality assessment tool based on six distinct affective systems. The six neural systems involved were labeled PLAY, SEEK, CARE, FEAR, ANGER and SADNESS. Spirituality has been integrated into the questionnaire as a seventh dimension because, in opinion of Panksepp and his colleagues is one of the most interesting human emotion. The aim of the present paper was introduce the validation of the Spanish version of Affective Neuroscience Personality Scales and their first psychometric results in a sample of 411 college students. Participants completed the Spanish version of ANPS, just as a personality scale of five factors (NEO-FFI R), and the Scales of Positive and Negative Affect (PANAS). The factor structure obtained and psychometric properties of the scales indicate that the Spanish version of the scales provides an effective tool to measure the seven dimensions of personality proposal in the original questionnaire. PMID- 22059337 TI - Intelligence impairment, personality features and psychopathology disturbances in a family affected with CADASIL. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a small-vessel disease of the brain that is characterized by headache, recurring lacunar strokes, mood changes and progressive cognitive deterioration. The disease is transmitted with an autosomal dominant pattern and usually starts during midadulthood (at 30-50 years of age). Cognitive deficits in patients with CADASIL develop slowly. The dementia causes frontal-like symptoms and it typically develops after a history of recurrent stroke. We describe three patients from one Spanish family affected by this disease. All three cases underwent comprehensive clinical and neuropsychological examination, and were monitored for seven years. The results obtained in this study describe a) a significant loss of the intelligence quotient (IQ) and noticeable damage to abstract ability (g factor), b) mood and psychopathological disturbances (major depression and dysthymia), and c) a personality with neurotic features. PMID- 22059338 TI - Psychometric analysis of the Catalan version of the Alabama Parenting Questionnaire (APQ) in a community sample. AB - The aim of this study was to adapt to Catalan the parents' and children's global report forms of the Alabama Parenting Questionnaire (APQ), using a community sample of 364 children between 10 and 15 years old and their families. Sociodemographic information (from parents) and the presence of externalizing problems (from parents and teachers) were collected. The results suggest a 3 factor structure corresponding to the scales of Positive Parenting Practices (PPP), Inconsistent and Negative Discipline (IND) and Poor Monitoring/Supervision (PMS). The internal consistency is acceptable in all the scales, except for the IND in the children's format. The scales also present good convergent and discriminant validity, and the relations with the external variable studied pointed in the expected direction: inefficient parenting practices are related to the presence of more behavior problems in children. To sum up, the Catalan version of the parents' and children's global report forms of the APQ are considered suitable for use in the area of children's and adolescents' behavior problems. PMID- 22059339 TI - Psychometric properties of the Turkish adaptation of the Mathematics Teacher Efficacy Belief Instrument for in-service teachers. AB - Teaching efficacy beliefs have attracted researchers' attention in recent decades because of its close association with and potential impact on the implementation of new ideas and skills in education. In the present study, we have explored the psychometric properties and construct validity of the Turkish adaptation of the Mathematics Teacher Efficacy Belief Instrument developed by Enochs, Smith, & Huinker (2000) for in-service mathematics teachers. The instrument distinguishes between two dimensions of efficacy beliefs for mathematics teachers: personal mathematics teaching efficacy and mathematics teaching outcome expectancy. The sample consisted of 1355 in-service elementary school teachers and middle school mathematics teachers from 368 schools. Exploratory and confirmatory factor analysis revealed a two-factor structure similar to that found in other studies. Also, scores from the two subscales indicated acceptable internal consistency. PMID- 22059340 TI - Psychometric properties of the Spanish version of the Running Addiction Scale (RAS). AB - Despite the growing number of Spanish people who organize their lives to prepare and participate in marathons, bringing to it a very committed lifestyle that, sometimes, go in detriment of their own health. In this instrumental paper, we the adaptation and testing of the psychometric properties of the Running Addiction Scale (RAS) in Spanish. To this end, we conducted two independent studies. The aim of the first was to present the first preliminary psychometric data (pilot sample of 174 marathon runners). Explained the process of translation, adaptation and content validity of items, we carried out a statistical analysis of these, an exploration of dimensional structure and analysis of the reliability of the instrument. In the second study (sample of 975 marathon runners), the aim was to analyze the internal structure of the instrument with confirmatory procedures. The Spanish version of the RAS showed acceptable levels of internal consistency, temporal stability, inter-item correlations and total scale score. Also provides evidences of construct validity. Slight differences were obtained by sex and age. These findings support the use of the Spanish version of RAS to assess individual differences in negative addiction to running. PMID- 22059341 TI - Psychometric update of the Social Anxiety Screening Scale (SASS/EDAS) in a Spanish adolescent population. AB - The aim of this work was to update the validation of the Social Anxiety Screening Scale (SASS/EDAS) in a sample of Spanish adolescents. To achieve this, one study with a sample of 1489 students in secondary education, of ages 14 to 17 years, were carried out. The psychometric properties of EDAS were examined through confirmatory factor analysis, reliability (Cronbach's alpha), temporal stability (test-retest), and concurrent criterion validity. The results supported the three independent-factor structure (avoidance, distress and interference), that showed best fit indices compared to alternative models. They also showed that the scores of participants on EDAS scales were reliable in terms of internal consistency (alpha > .80) and moderately reliable concerning temporal stability (r = .48-.60) over a five-week period. The correlations between the EDAS factors and other social anxiety measures were positive and significant. Data provide empirical evidence of the estimation of reliability and validity of this scale. Future work should extend the validation of the EDAS in clinical samples. PMID- 22059342 TI - Validity of the Parenting Stress Index-Short Form in a sample of Spanish fathers. AB - The purpose of this study was to analyze the psychometric properties of the Spanish version of the Parenting Stress Index-Short Form in a sample of 115 fathers of infants aged between ten and thirty-nine months old. The exploratory factor analysis revealed three reasonably distinct factors, as in the original version of the instrument. The three extracted factors: Parental Distress, Parent Child Dysfunctional Interaction and Difficult Child accounted for 47.48 % of the variance. The internal consistency coefficients were high in each factor or subscale. These results provided empirical evidence in favour of the reliability and validity of the Parenting Stress Index-Short Form in Spanish fathers, and can be useful to elucidate the mechanisms through which stress impacts parenting and permitting to develop more targeted interventions for infants and their families. PMID- 22059343 TI - Avoidance and activation as keys to depression: adaptation of the Behavioral Activation for Depression Scale in a Spanish sample. AB - In this paper we present the adaptation of the Behavioral Activation for Depression Scale (BADS), developed by Kanter, Mulick, Busch, Berlin, and Martell (2007), in a Spanish sample. The psychometric properties were tested in a sample of 263 participants (124 clinical and 139 non-clinical). The results show that, just as in the original English version, the Spanish BADS is a valid and internally consistent scale. Construct validity was examined by correlation with the BDI-II, AAQ, ATQ, MCQ-30, STAI and EROS. Factor analysis justified the four dimensions of the original instrument (Activation, Avoidance/Rumination, Work/School Impairment and Social Impairment), although with some differences in the factor loadings of the items. Further considerations about the usefulness of the BADS in the clinical treatment of depressed patients are also suggested. PMID- 22059344 TI - Factorial validity of the Job Expectations Questionnaire in a sample of Mexican workers. AB - The aim of this study was to examine the factorial validity of the Job Expectations Questionnaire (Cuestionario de Expectativas Laborales CEL) in a sample of Mexican workers. Following a cross validation approach, two samples were used in the study. The first sample consisted of 380 professionals who mainly performed administrative work in the Health Services in Puebla-Mexico. The second sample comprised 400 health professionals from the Hospital de la Mujer in Puebla-Mexico. Exploratory factor analysis yielded a three-factor solution, accounting for 51.8% of the variance. The results of confirmatory factorial analysis indicate that the three-factor model provided the best fit with the data (CFI = .96, GFI = .95, NNFI = .95, RMSEA = .04), maintaining the structure with 12 items. The reliability of the questionnaire and the diverse subscales showed high internal consistency. Significant correlations were found between job expectations and autonomy, vigor, dedication, and absorption, providing evidence of its construct validity. The evaluation of the psychometric qualities confirms this questionnaire as a valid and specific instrument to measure job expectations. PMID- 22059345 TI - A new approach for differential item functioning detection using Mantel-Haenszel methods. The GMHDIF program. AB - To date, the statistical software designed for assessing differential item functioning (DIF) with Mantel-Haenszel procedures has employed the following statistics: the Mantel-Haenszel chi-square statistic, the generalized Mantel Haenszel test and the Mantel test. These statistics permit detecting DIF in dichotomous and polytomous items, although they limit the analysis to two groups. On the contrary, this article describes a new approach (and the related software) that, using the generalized Mantel-Haenszel statistic proposed by Landis, Heyman, and Koch (1978), permits DIF assessment in multiple groups, both for dichotomous and polytomous items. The program is free of charge and is available in the following languages: Spanish, English and Portuguese. PMID- 22059346 TI - Testing equivalence with repeated measures: tests of the difference model of two alternative forced-choice performance. AB - Solving theoretical or empirical issues sometimes involves establishing the equality of two variables with repeated measures. This defies the logic of null hypothesis significance testing, which aims at assessing evidence against the null hypothesis of equality, not for it. In some contexts, equivalence is assessed through regression analysis by testing for zero intercept and unit slope (or simply for unit slope in case that regression is forced through the origin). This paper shows that this approach renders highly inflated Type I error rates under the most common sampling models implied in studies of equivalence. We propose an alternative approach based on omnibus tests of equality of means and variances and in subject-by-subject analyses (where applicable), and we show that these tests have adequate Type I error rates and power. The approach is illustrated with a re-analysis of published data from a signal detection theory experiment with which several hypotheses of equivalence had been tested using only regression analysis. Some further errors and inadequacies of the original analyses are described, and further scrutiny of the data contradict the conclusions raised through inadequate application of regression analyses. PMID- 22059347 TI - The use of the effect size in JCR Spanish journals of psychology: from theory to fact. AB - In 1999, Wilkinson and the Task Force on Statistical Inference published "Statistical Methods and Psychology: Guidelines and Explanation." The authors made several recommendations about how to improve the quality of Psychology research papers. One of these was to report some effect-size index in the results of the research. In 2001, the fifth edition of the Publication Manual of the American Psychological Association included this recommendation. In Spain, in 2003, scientific journals like Psicothema or the International Journal of Clinical and Health Psychology (IJCHP) published editorials and papers expressing the need to calculate the effect size in the research papers. The aim of this study is to determine whether the papers published from 2003 to 2008 in the four Spanish journals indexed in the Journal Citation Reports have reported some effect-size index of their results. The findings indicate that, in general, the followup of the norm has been scanty, though the evolution over the analyzed period is different depending on the journal. PMID- 22059348 TI - Innate immunity in obese asthmatic allergic and nonallergic adults. AB - Obesity is characterized by activation of the innate immune responses and low grade systemic inflammation with increased levels of inflammatory cytokines. In the past two decades, the prevalence of both asthma and obesity has increased dramatically. The aim of the present study is to examine the relationship between innate immunity, obesity and asthma in allergic and non allergic obese persons by estimating interleukin-6 (IL-6) and C-reactive protein (CRP) levels as markers of innate immunity. The study included 2 groups of asthmatic patients; 50 obese asthmatic and 50 lean asthmatic patients. The obese asthmatic group included 25 allergic obese and 25 non-allergic obese asthmatics. Similarly the lean asthmatic group included 25 allergic and 25 non-allergic lean asthmatics. Body mass index (BMI), skin prick test, serum total IgE, peak expiratory flow rate (PEFR), interleukin-6 (IL-6) and C-reactive protein (CRP) levels were all assessed. A significant difference was found between allergic and non-allergic obese asthmatics and between allergic and non-allergic lean asthmatics as regards IgE, IL-6 and CRP (P=0.000). Comparison between allergic obese asthmatics and allergic lean asthmatics as regards BMI, IL-6 and CRP revealed high significant differences (P=0.000). In contrast no significant differences existed between them as regards IgE, PEFR (P=0.621, P=0.321 respectively). Comparison between non allergic obese asthmatics and non-allergic lean asthmatics as regards BMI, IL-6 and CRP levels revealed highly significant differences (P=0.000). While no significant difference existed between them as regards IgE and PEFR (P=0.14, P=0.336 respectively). A significant negative correlation was found between PEFR and IgE in all groups (P=0.000) and negative correlation between PEFR and IL-6, CRP in all groups (P=0.000) except for allergic obese asthmatics group. Meanwhile, there was a significant positive correlation between BMI and IL-6 and CRP in both allergic and non-allergic obese asthmatics (P=0.000). In conclusion, obesity is associated with activation of the innate immune system leading to release of inflammatory cytokines more in non-allergic obese than allergic obese asthmatics. Control of obesity in such patients may lead to control of asthma. PMID- 22059349 TI - CD11c+ and CD123+ dendritic cell subsets in peripheral blood of lung cancer patients. AB - Dendritic cells (DCs) play a central role in antitumor immune responses. Recent studies however have emphasized an immunosuppressive tumor influence on DCs in various types of cancer. We evaluated the percentages of myeloid and plasmacytoid related DCs in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Myeloid CD11c+ DCs (mDC) and plasmacytoid CD123+ DCs (pDC) cells were assessed by Flowcytometry in peripheral blood of twenty untreated lung cancer patients (13 NSCLC and 7 SCLC) and 15 healthy subjects. Lower percentages of pDCs and mDCs were found in patient with NSCLC and SCLC as compared to controls, with significant value only between NSCLC patients and controls (P= 0.001and P=0.000 respectively). The percentages of pDCs and mDCs subsets were significantly lower in patient with SCLC than NSCLC (P=0.013 and P=0.005 for pDCs and mDCs respectively). Our results suggest that NSCLC and SCLC might hamper the maturation of DCs, thus escaping an efficient immune response. PMID- 22059350 TI - Diminished absolute counts of CD56dim and CD56bright natural killer cells in peripheral blood from Egyptian patients with hepatocellular carcinoma. AB - Natural killer cells (NK) as components of the innate immunity substantially contribute to anti-tumor immune responses, NK cell subpopulations can be defined on the basis of the relative expression of CD16 and CD56 markers. Earlier research demonstrated a dramatic reduction in the frequency of peripheral blood CD56dimCD16+ NK subsets in hepatocellular carcinoma (HCC) patients compared with healthy subjects. We aim to assess the relative and absolute counts of natural killer cells subsets in hepatitis C-related HCC among Egyptian patients. Flowcytometric analysis of peripheral blood NK subsets was performed for HCV with HCC patients (n=20) and HCV without HCC patients (n=14) as compared to healthy control subjects (n=152). We found that HCC patients displayed a marked reduction in the relative frequency of peripheral CD56im subsets compared with healthy subjects. Moreover, there was a significant reduction in the absolute counts of CD56dim16+, CD56dim16- and CD56bright. In conclusion, this study demonstrated that the absolute counts of dim and bright NK cell subsets were decreased in different proportions in patients with HCV-related HCC that refers to a possible role for these cells, particularly CD 56 bright cells, in the immune response to HCC. This might aid in developing new therapeutic strategies targeting both NK subsets for HCC. PMID- 22059351 TI - CD40 ligand, Bcl-2 and apoptosis in B-chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is a haematopoetic neoplasm caused primarily by defects in apoptosis mechanisms and complicated by progressive marrow failure, immunosupression and increased resistance to chemotherapy. The CD40-CD40 ligand (CD40L) interaction has been shown to significantly increase antigen presentation in normal and malignant B-cells and it is a powerful regulator of cell survival. Bcl-2 expression is common in CLL and is associated with decreased overall survival. Our objective was to asses CD40 ligand (CD154) and Bcl-2 expressions and their correlation with clinical and laboratory features in CLL patients. This study was conducted on 40 subjects, including 10 healthy volunteers as the control group and 30 patients presented with de novo chronic lymphocytic leukemia (CLL), all of them were subjected to thorough history taking, full clinical examinations, routine laboratory investigations and flowcytometric assessment of CD40L and Bcl-2 on lymphocytes. There was a highly significant increase in TLC, absolute lymphocytic count, serum LDH, B2-microglobulin and Bcl-2 expression (P<0.001); there was a significant increase in CD40L expression (P<0.05); whereas there was a highly significant decrease in hemoglobin concentration and platelets count between the study group (P<0.001). There was no significant difference as regard direct Coombs' test between both groups. There was no significant relation between CD154 expression and clinical findings, Rai staging system and other laboratory parameters. CD40L expression is increased with staging of Modified Rai staging system but not reaching the significant level. There was no significant correlation between CD154 expression and some of clinical and laboratory parameters, whereas there was only significantly negative correlation between Bcl 2 expression and both haemoglobin concentration and platelets count (P<0.001). Combination of Bcl-2 antisense oligonucleotide with conventional chemotherapeutic drugs may enhance the cytotoxicity of these drugs and induces apoptosis. PMID- 22059352 TI - Tumor-derived CCL-2 and CXCL-8 as possible prognostic markers of breast cancer: correlation with estrogen and progestrone receptor phenotyping. AB - Prognosis of breast cancer is believed to be a multifactorial process best achieved by complex factors including host and tumor-derived biomarkers together with traditional clinicopathological parameters and tumor histologic markers. The present study aimed at evaluating the prognostic significance of chemokine ligand 2 (CCL-2) and interleukin-8 (CXCL-8) expression in extracts of breast carcinomas through correlation with clinicopathological aspects as well as estrogen receptor (ER) and progesterone receptor (PR) phenotyping. The study was conducted on 30 Egyptian breast cancer patients diagnosed by fine needle aspiration cytology (FNAC) and subjected to modified radical mastectomy. Excised tissues were used to prepare tissue sections and extracts for histopathological and immunohistochemical studies. Expression of CCL-2 and CXCL-8 was determined by enzyme-linked immunosorbent assay (ELISA). 26 patients had invasive ductal carcinoma, grades II and III with metastasis to axillary lymph nodes and ER and PR positive phenotype. Expression of CCL-2 and CXCL-8 was significantly influenced by patient's age, menopausal status, nodal involvement, tumor grade and the ER phenotype. In contrast, it was not affected by either tumor size or PR staining pattern. Both chemokines correlated positively to each other and to tumor grade and negatively to age, menopausal status of patients and ER phenotyping. It is concluded that the angiogenic chemokine CXCL-8 and the macrophage chemoattractant CCL-2 might be useful prognostic markers where their routine follow up might be of importance in assessment of tumor aggressiveness in clinical settings. PMID- 22059353 TI - Investigation of adult-sera for the presence of anti-Cryptosporidium antibodies. AB - Cryptosporidiosis is an acute diarrhoeal disease caused by Cryptosporidium spp for both human and animals. Typically, the duration of diarrhoeal illness and ultimate outcome of intestinal cryptosporidiosis depend on the immune status of the patient. Random serology-based studies in humans and animals have suggested that infection with this organism is common during a life time. 130 serum samples of adults, (18-30 years) from two main public hospitals at Jeddah City, Saudi Arabia were recruited to participate in the study. The aim was to identify the sero-prevalence of cryptosporidiosis infection and determine factors associated with increased risk of the infection. Western Blot analysis (WB) with two different Cryptosporidium antigen markers; the 15-17 KDa and the 27 KDa, were used. Among participants, 8.5 % had antibodies to the 15 KDa, 23.8 % had antibodies to the 27 kDa, 34.6 % were sero-positive to both antigens, and 33.1 % were sero-negative to both antigens. Source of drinking water with a strong association with drinking tap water was the only factor significantly associated with seropositivity to cryptosporidiosis infection (OR= 37.33, P< 0.001). PMID- 22059354 TI - Peripheral blood mononuclear cells serve as a possible extrahepatic site for hepatitis C virus replication. AB - Hepatitis C virus (HCV) is thought to have a strong tropism for hepatic tissue but also replicative intermediates are found in extrahepatic tissues suggesting active viral replication in these cells. The aim of the study is to confirm that HCV can infect and replicate in the peripheral blood mononuclear cells (PBMCs) as one of the possible sites of extrahepatic hepatitis C virus replication during the natural course of infection which may serve as a source of virions causing reinfection. Reverse transcriptase Polymerase chain reaction (RT-PCR) for detection of positive and negative strands of HCV-RNA in PBMCs was done for 30 patients with chronic HCV infection admitted to Ain Shams University Hospitals and the results were compared with those from 20 healthy controls matched in age and sex. Our results revealed statistically significant association between both HCV-RNA positive strand and negative strand and both serum HCV-RNA and HCV Antibody (Ab) (P<0.01).Moreover the association between the presence of HCV positive- and negative-strand RNA in PBMCs was statistically significant (P<0.01). Finally the correlation between HCV positive and negative stranded RNA in PBMCs and extrahepatic complications was statistically significant (P<0 .01). In conclusion our results support previous observations indicating that HCV can infect PBMCs. This is reflected by a higher frequency of extrahepatic complications and diseases associated with chronic HCV infection. PMID- 22059355 TI - Immunomodulatory effects of secondary hyperparathyroidism on circulating CD4+ and CD8+ T-lymphocytes in chronic renal failure patients. AB - The immunomodulatory effects of parathyroid hormone (PTH) in patients with end stage renal disease (ESRD) is controversial. This study was carried out to investigate the effect of PTH levels on the circulating CD4+, CD8+ T cell counts (%) in patients with chronic renal failure (CRF) on regular hemodialysis ((HD). The study included 22 patients with serum levels of PTH < 300 pg/ml (group 1), 18 patients with PTH > 300 pg/ml (group II) and 10 age and sex matched normal controls (group III). Chemiluminescence and flowcytometry assays were performed for determination of serum PTH levels and T cell subset counts respectively. The mean (%) of total lymphocyte, CD4+, CD8+ and CD4?CD8 ratio of group I were (81.68+/- 9.38), (52.00+/-6.24), (27.13+/- 6.31) and (1.99+/-0.42) respectively, as compared to (73.83+/-13.30), (46.05+/-8.59), (23.05+/-4.63) and (2.03+/-0.41) respectively in group II. Values of group I and II were significantly (P<0.001) lower than controls (88.50 +/- 6.02), (63.30 +/- 6.44), (36.80 +/- 6.44) and (1.76+/-0.36) respectively. In group II, the reduction was significantly (P<0.001) prominent in patients with high PTH levels, with significant inverse correlations (P<0.001) between PTH and % of total lymphocyte (r= -0.93), CD4+ (r= -0.74) and CD8+ % (r=-0.69). In conclusion, increased level of PTH in CRF patients on hemodialysis is associated with lymphopenia and reduction in CD4+ & CD8+ subsets of T cells. Monitoring circulating PTH levels in such patients can restore their immune competence. PMID- 22059356 TI - Soluble intercellular adhesion molecule-1 (slCAM-1) for early diagnosis of neonatal infections. AB - We investigated the validity of circulating soluble intercellular adhesion molecule-1 (slCAM-1) as an early immunological marker of neonatal sepsis as compared to C-reactive protein (CRP), immature to total neutrophils ratio (IlT) and blood culture assays. The study included 28 full term neonates with clinical manifestations of sepsis, 10 of them had suspected sepsis "Group I" with negative blood culture, positive CRP during 1st week of life and one or more risk factors for infections. The other 18 neonates had proven sepsis "Group II"; with positive blood culture and positive CRP. 14 normal age and sex matched controls "Group III" were also included. Serum slCAM-1 concentrations (ng/ml) were measured using enzyme linked immunosorbent assay (ELISA) in two successive blood samples; before (S1) and one week after (S2) the start of antibiotics respectively. The mean value of I/T ratio was significantly higher in both SI and S2 (P<0.05; P<0.001 respectively) in septic neonates compared with controls. In addition, a significant difference (P<0.05) was detected in S2 between mean CRP levels in group I (9.6+/-15.7 mg/dl) and group II (17.3+/-30.0 mg/dl). The mean values of slCAM-1 in (Sl) of septic groups I and II (445.7+/-138.5 and 512.8+240.9 ng/ml respectively) were significantly higher (P<0.05) than those of control group (364.0+/-67.4). In contrast, in (S2) insignificant differences were detected between both groups (392.6+/-149.8 and 420.0+/-184.7 respectively) and controls. A positive correlation was revealed between CRP and slCAM-1 values in (Sl) (r=0.3, P<0.05). Positive correlations were also detected between slCAM-1 levels and leukocytic counts (r=0.3, P<0.05) and CRP (r=0.5, P<0.001) in (S2) while, negative correlation was detected between slCAM-1 levels and platelet counts (r= 0.5, P<0.001). In conclusion, serum concentration of ICAM-1 is a potential marker for diagnosis of neonatal sepsis at its early stages. PMID- 22059357 TI - Dendritic cells-based T-cell immune response for the variable region of immunoglobulin light chain of myeloma and lymphoma cell lines. AB - The present work supported and extended a previous study (used VLIg gene segment type VkappaIV) and indicated that a considerable (P<0.001) and specific autologous T-cell proliferation, proliferative index (PI) ranged from 386.0 to 399.5 at 20% dendritic cells (DCs):T-cells ratio, restricted mainly (>80%) to the major histocompatibility complex (MHC) class-I molecules can be elicited in vitro against other different VLg gene segments (VkappaI, VkappaIII and Vlambda2) of myeloma and lymphoma cell lines through a retroviral transduction of human DCs generated from CD34+ progenitor cells by phorbol ester (PMA) and under serum-free conditions. This study also showed a lesser proliferation, but significant (P<0.05), restricted to MHC class-II molecules and specific for VLIg gene segments. The obtained proliferation was almost completely blocked (approximately 95%, P<0.001) by anti-CD86 monoclonal antibodies, which confirmed the critical role of the CD86 costimulatory molecules in the activation of naive T-cells. The resulting immune responses did not significantly differ (P>0.05) among the different types of VLIg gene segments, as VLIg-transduced DCs equally coexpressed the VLIg genes and CD86 costimulatory molecules. In conclusion, the present study could provide the basis of a VLIg-based immunotherapy in plasma cell and B-cell malignancies. PMID- 22059358 TI - Human leukocyte antigen and autoantibodies association with juvenile systemic lupus erythematosus. AB - In this study we investigated the association between autoantibodies production and MHC class II alleles in fifty three Egyptian children patients with systemic lupus erythematosus (SLE). A significant association was found between expression of HLA-DR4 and HLA-DR13 genes and the generation of anti-ribonucleoprotein and IgG cardiolipin antibodies respectively, in contrast to the negative association of antinuclear antibodies (ANA) with HLA-DR8 and HLA-DR14. Analysis of HLA-DR alleles and autoantibodies frequencies in relation to different clinical manifestations revealed significant association between HLA-DR13 and vasculitis, while, HLA-DR1 and HLA-DR3 were significantly associated with seizures. In contrast, HLA-DR8, HLA-DR4 and HLA-DR52 alleles were associated with significant protection from arthritis, abnormal kidney function and neuropsychiatric disorders, respectively. SLE autoantibodies, namely anti-DNA antibodies were significantly associated with disturbed kidney function tests and the occurrence of seizures. In contrast, nucleosome antibodies showed no association with renal involvement in childhood onset systemic lupus erythematosus. PMID- 22059359 TI - Influence of HCV infection on insulin-like growth factor 1 and proinflammatory cytokines: association with risk for growth hormone resistance development. AB - Communications between the endocrine, immune systems and the liver have been postulated. The liver is the central organ in growth hormone/insulin-like growth factor (GH-IGF) axis. Infection with hepatitis C virus (HCV) can lead to liver problems. Although proinflammatory cytokines are an integral part of inflammation in chronic liver diseases, their involvement in mediating hepatic GH resistance during HCV infection remains to be elucidated. To address this issue, our study aimed at evaluating the influence of HCV infection on serum profile of IGF-1, TNF alpha and IL-6 to assess their possible relation to hepatic dysfunction and GH resistance development. Twenty-five chronic HCV patients were studied together with 15 healthy control subjects. Serum concentration of IGF-1, TNF-alpha and IL 6 was determined by ELISA. HCV viral load was assessed by Real-time polymerase chain reaction using TaqMan probe technology. Basal serum GH levels were determined by a chemiluminescence assay and serum aminotransferases' activities were also measured. TNF-alpha and IL-6 demonstrated higher serum levels, while IGF-1 levels were significantly lower in HCV patients compared to healthy controls. A statistically significant positive correlation was observed between GH and IL-6 levels (P<0.05), a similar trend was found between GH levels, GH/IGF 1 ratio and AST/ALT ratio (P<0.01, P<0.01, respectively). A significant negative correlation was observed between HCV viral load and GH levels (P<0.05). The progressive increase in HCV viral load matches the decrease in circulating IGF-1 levels but without reaching statistical significance. We conclude that the GH insensitivity could be induced by HCV infection and mediated by proinflammatory cytokines through their possible role in blunting the hepatic response to GH. This crosstalk between proinflammatory cytokines and GH-IGF-1 axis could be responsible for triggering impaired glucose metabolism and diabetes later on in chronic HCV infection. PMID- 22059360 TI - Association of beta-defensin 1 single nucleotide polymorphism with atopic dermatitis. AB - Atopic dermatitis (AD) is a chronic relapsing, pruritic, inflammatory skin disease, which results from a complex interplay between genetic and environmental factors. Defensins are broadly dispersed family of antimicrobial peptides which are classified into 2 distinct families: the alpha-defensins and the beta defensins. The primary function of defensins is to protect the skin from invasion by foreign pathogens. Previous studies suggested that single nucleotide polymorphisms (SNPs) of the beta-defensin 1 gene (DEFB1) could be involved in the development of AD. The Aim of the study is to examine DEFB1 gene to gain a better understanding of their role in the pathophysiology of AD patients and their involvement in AD susceptibility and severity. 35 atopic patients and 10 healthy volunteers as controls were investigated. They were subjected to analysis of absolute eosinophil count, total and specific IgE and detection of Beta-defensin 1 gene polymorphism at position 692 and 1654 using PCR amplification and restriction analysis. We observed significant difference in the distribution of the DEFB1 AIG polymorphism at 692 (P<0.01) in AD patients compared to controls, but not at 1654. A statistical significant association between DEFB1 692 GG genotype and elevated total serum IgE level (P<0.01), and between DEFB1 692 GG and AG genotypes & 1654 AA genotype and high absolute eosinophil count (P<0.05) were found. Concerning Specific IgE there was significant association between DEFB1 692 GG genotype and positive specific IgE to dermatophytes and HDM (House Dust Mite) (P1<0.01) while DEFB1 1654AA genotype shows significant association with positive specific IgE to cockroaches (P<0.05). Regarding SCORAD severity index, there was significant statistical association between DEFB1 692 GG and AG & DEFB1 1654 AA and AG genotype with severe AD disease (P<0.05). The correlation between atopic markers and SCORAD severity index shows that there was a significant statistical relationship between serum levels of total IgE (P<0.01), absolute eosinophil count (P<0.01), specific IgE to cat (P<0.05), HDM (P<0.01) and cockroaches (P<0.01) and SCORAD. Our findings support previously studies suggesting that DEFB1 gene is one of the candidate genes for atopy. G allele at site 692& AA genotype at site 1654 may be useful as markers for AD susceptibility and severity PMID- 22059361 TI - Preparation and evaluation of specific polyclonal antibodies to H5N1 subtype of the avian influenza virus in Egypt. AB - Influenza A virus continue to cause widespread morbidity and mortality. The unprecedented spread of highly pathogenic avian influenza virus subtype H5N1 in Egypt is threatening poultry and public health systems. Effective diagnosis and control management are needed to control the disease. To this end, polyclonal antibodies (PAbs) were developed against the H5N1 avian influenza virus (AIV) and used in an enzyme-linked immunosorbent assay (ELISA) to detect the H5 viral antigen. A group of rabbits were immunized with H5N1 vaccine to obtain PAbs as the detector antibody after conjugation with horse radish peroxidase and fluorescein isothiocyanate (FITC). The conjugated PAbs proved to be specific for the detection of AIV in field specimens, and results were confirmed using reference antisera obtained from Veterinary Lab in Weybridge. Specimens collected from different governorates of Egypt and tested positive for AIV by haemagglutination test were used to evaluate the produced PAbs. The detection limit of ELISA using the prepared peroxidase conjugated PAbs was 1:100,000, while the limit using fluorescein conjugated PAbs was 1:10,000. Extracts from pharyngeal-tracheal mucus of apparently healthy chickens mixed with H5 AIVs also yielded positive signals in ELISA. Such data suggest that these PAbs are useful in the surveillance and diagnosis of AIV in birds in Egypt. PMID- 22059362 TI - [Functional magnetic resonance imaging for cortical mapping in epilepsy]. AB - It is not only the total curative resection of pathological tissue or the minimization of symptoms to be considered in epilepsy surgery or other neurosurgical procedures, it is equally desirable to maintain the best possible quality of life. Cortical mapping methods can help achieve this goal by delineating eloquent areas, i.e. brain regions that are vital for providing an acceptable quality of life, albeit not prone to compensatory reorganization. These areas include among others the Broca and Wernicke regions for speech, the primary motor, sensory and visual cortices. Functional MRI gained importance in the last decade as a non-invasive clinical cortical mapping technique. This method is capable of localizing cortical areas selectively activated by a given task condition. Thus, selecting appropriate tasks can help mapping eloquent brain regions. Using functional MRI provides information that is complementary to other mapping methods. Moreover, it can replace invasive methods such as the Wada test. Here, we explain the background of functional MRI, compare it to other clinical mapping methods, explain the intricacies of paradigm selection, and show the limitations of the technique while also pointing out alternative uses. PMID- 22059363 TI - [Magnetic resonance measuring and analitic methods in epilepsy]. AB - Neuroradiology and magnetic resonance imaging (MRI) as its leading tool play a basic role in the diagnostics of epilepsy. The result of the MRI examination is of utmost importance in patients with therapy resistent focal epilepsy possibly requiring neurosurgical intervention. Based on the continuously developing MRI techniques, we can use an optimal imaging protocol. Cerebral structures can be evaluated on a microanatomical level on high-resolution images with thin slices. The three-dimensional (3D) sequence has high spatial resolution, properly distinguishes cerebral grey and white matter, provides the possibility of surface rendering and volumetry, as well as an anatomical basis for other methods like tractography, functional MRI and neuronavigation. Diffusion weighted and diffusion tensor imaging (DWI, DTI) and tractography has an important role in differential diagnostics and tractography visualizes the main white matter tracts and their relation with brain pathologies. MR perfusion (MRP) provides help in differential diagnostics and may have a future role in the determination of the epileptogenic focus in multifocal pathologies. MR spectroscopy (MRS) is important in differential diagnostics, lateralization of focal epilepsy and in the confirmation of hippocampal sclerosis. Several of these methods need special hardware, software and expertise, but the basic MRI protocol for epilepsy can be implemented in all modern MR scanners of middle or high field strength. PMID- 22059364 TI - [LORETA (low resolution electromagnetic tomography): a three-dimensional EEG source localization method]. AB - The author presents a brief overview of the EEG source localization method LORETA (Low Resolution Electromagnetic Tomography) with special reference to the not widely discussed data. PMID- 22059365 TI - [The methodology and objectives of registrating high frequency oscillation in epilepsy]. AB - Technological advances in digital EEG allowed the recording the full frequency band of the EEG. Activity beyond the traditional 0.3-70 Hz band reflects both physiological and pathological processes. High frequency activity recorded from the epileptic brain has been related to both epileptogenicity and epileptogenesis. The article reviews research avenues, clinical applications, and the methodology of detecting and quantifying high frequency activity. PMID- 22059366 TI - [Prolonged EEG-monitoring]. AB - Prolonged EEG monitoring and video-EEG monitoring are basic methods on the level of epilepsy centers. These methods are able to make differences between epilepsy and non epileptic paroxysmal manifestations like psychogenic non epileptic seizures, parasomniac phenomena, narcolepsy. The application of the method, at least the video-EEG variant, needs team work, high level organisation, highly educated staff and high tech electrographic devices. Running the method even with these requirements is beneficial from the cost-benefit aspect as well. PMID- 22059367 TI - [Role of deep brain stimulation in epilepsy]. AB - The deep brain stimulation (DBS) is an emerging treatment option in brain disorders in which randomized multicenter trials proved its efficacy leading to licensing different DBS methods in various brain diseases. More recently more and more brain structures have become candidates for being "target" in a possible DBS treatment of epilepsy. At present, only the DBS of the anterior nucleus of the thalamus (ANT) can be considered as a proved method for epilepsy treatment. Other potential targets for DBS treatment in epilepsy are the subthalamic nuclei, and the amygdala-hippocampus complex. There are some ongoing randomized studies to investigating their therapeutical role. The therapeutical outcome of ANT-DBS treatment in drug-resistant epilepsy seems to be better than the new antiepileptic drugs, but much worse than the results of a potential epilepsy surgery. At about 10% of patients may become seizure-free and 50% of patients may have a significant improvement. Nowadays ANT-DBS should be considered as an "ultima ratio" in those adult drug-resistant epilepsy patients with normal intelligence in which neither new antiepileptic drugs nor resective epilepsy surgery are a reasonable therapeutical options. PMID- 22059368 TI - [The clinical utility of genetic testing in epilepsy]. AB - We summarize those epilepsies, in which genetic testing has clinical significance. Different types of genetic tests are presented. Na-channel epilepsies include different clinical entities, the exact genetic diagnosis is relevant in the prognosis, genetic counseling, as well in the therapeutic decision--as Na-channel blockers may worsen them. Molecular genetic tests are available for most of the malformations of cortical development, important for genetic counseling and prenatal diagnosis. Molecular genetic testing of progressive myoclonic epilepsies, which may be difficult to differentiate clinically is almost complete. For some neonatal/infantile epileptic encephalopathies, for most of the neurometabolic disorders, molecular genetic tests are available, so are cytogenetic tests for chromosomal abnormalities accompanied with epilepsy. The clinical significance of the genetic diagnostic of rare, focal inherited epilepsies is limited, their importance is mostly in epilepsy pathophysiology research. The genetic background of the common idiopathic generalized epilepsies is unrevealed so far. PMID- 22059369 TI - [Critical analysis of types and objectives of phamacological trials]. AB - Antiepileptic drug randomized controlled trial (RCT) design has been criticized in the near past. Designs emphasize conventions and regulations more than clinical aspects. In the new study that scrutinized RCT patient recruitment has also raised important ethical issues. The time has come when changes in RCT design seem imperative. PMID- 22059370 TI - [New antiepileptic drugs, and therapeutic considerations]. AB - Epilepsy is not a singular disease, but a variety of disorders. It affects up to 0.5% of the population. Over the past decade, researchers have made great advances in the field of epilepsy. These have been accompanied by the licensing of a great number of antiepileptic drugs. However, despite these efforts, up to 15-20% of patients have refractory epilepsy. The novel antiepileptic drugs must suit several requirements: higher efficacy, especially in resistant cases, better tolerability, and improved pharmacokinetic properties. Recently, three new drugs have been introduced to the market. Retigabine is a carbamic derivate, and its anticonvulsive properties are largely due to its ability to prolong the opening of neuronal voltage-gated potassium Kv7.2 and Kv7.3 channels. Lacosamide is a functionalized amino acid, and selectively enhances voltage-gated sodium channel slow inactivation. Eslicarbazepine acetate is a new member of the dibenzazepine family, and blocks the fast inactivated voltage-gated sodium channel. All three of them differ from the foregoing agents in several important ways, including new mechanism of action (retigabine, lacosamide), or pharmacokinetics (eslicarbazepine acetate). These novel anticonvulsants appear to be a safe and effective addition to the armamentarium for the treatment of patients with refractory epilepsy. However, it will take the consideration of new concepts in shaping the new therapeutic algorithm. PMID- 22059371 TI - [The role of neuronavigation in the assessment and surgical treatment of drug resistant epilepsy]. AB - For localizing the epileptogenic zone in cases of focal epilepsies detailed clinical investigations, imaging studies and electrophysiological methods are in use. In lesional epilepsies the intrapreoperative localization of the lesion and it's location to the eloquent cortex is essential for the neurosurgeon. The development in image guided neurosurgery lead us to use neuronavigation systems to localize intracerebral lesions or functionally eloquent cortical areas or subcortical pathways during surgery. Neuronavigation brought changes in preoperative evaluation and in resective surgery in epilepsy as well. In this article we describe the basics of neuronavigation and enhance the advantages of the technique in epilepsy surgery during the presurgical evaluation with invasive electrodes, in resective surgery and DBS for epilepsy. PMID- 22059372 TI - [Neuropsychological methods and trends in epilepsy management]. AB - Neuropsychological assessment makes its own valuable contribution to diagnosis in epilepsy, and the integration of those findings with the data from multiple sources provides the most comprehensive picture for a given epilepsy patient. The objective of this paper is to define and summarize the role and methods of neuropsychological assessment, and to present recommendations on themes for future clinical research in the neuropsychology of epilepsy. PMID- 22059373 TI - [Oligoepilepsy: a real entity or the benign form of epileptic disorder?]. AB - BACKGROUND AND PURPOSE: Although oligoepilepsy (OLE) is a used term in many protocols, guidelines and the everyday routine, it is found practically nowhere in the scientific literature. The aim of our study is to investigate and evaluate of the main characteristics of his subcategory of epilepsy. We try to find answer to the basic question of not only theoretical but also great practical importance whether the OLE does really exist, is it an independent entity of epilepsy or only its general benign clinical presentation. METHODS: We considered OLE if the patients had two seizures maximally in the last year of their course. We counted only the two most severe clinical types, the generalized tonic-clonic and the complex partial seizures. We divided the OLE into two subtypes: those patients who had OLE from the beginning of their epilepsy (OLE1) and those in whom the OLE was the result of the treatment (OLE2). We retrospectively analysed the data of 817 "OLE-suspicious" patients taken from our EPIMED database. RESULTS: We found 47 patients met the inclusion criteria (OLE1 = 34, OLE2 = 13). OLE patients did not differ from the general epileptic population according to the age and gender, the type of seizures, the electro-clinical diagnosis and the possible cause of their first seizure. But we found statistically significant differences in two measures. In OLE, far less seizure provoking factors were found in the sporadic seizures. Concerning the social conditions: while the range of employees was equal, the vast majority of OLE patients were able to work at their level of education. CONCLUSION: We found that more than 5% of people with epilepsy can belong to the OLE category. In the majority of OLE patients the seizure frequency is low from the beginning of the disease. The sporadic seizures in OLE are generally not provoked. The chances of OLE patients in the world of job are better for the OLE patients. In our opinion OLE rather seems to be an independent entity among epilepsy. Therefore larger prospective studies are needed to the exact description of OLE and to establish the special standards for the everyday medical practice. PMID- 22059374 TI - [New generation antiepileptics: what do they offer in terms of improved tolerability and safety?]. PMID- 22059375 TI - Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes. AB - Systematic ligand development has led to the identification of novel mono-N protected amino acid ligands for Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes. A diverse range of organoboron reagents can be used as coupling partners, and the reaction proceeds under mild conditions. These results provide a new retrosynthetic disconnection for the construction of enantioenriched cis substituted cyclopropanecarboxylic acids. PMID- 22059376 TI - Distinguishing groups of children with persistent speech disorder: findings from a prospective population study. AB - As part of a large-scale study of children's development, 7390 children were assessed on a range of speech tasks. These were used to identify three groups of children with speech errors within the sample: persistent speech disorder (PSD); speech errors but below the threshold for classification as persistent speech disorder (non-PSD); and common clinical distortions only (CCD). These three groups were compared on demographic factors, performance on IQ, non-word repetition, and diadochokinetic tests. Findings showed that the PSD group and the non-PSD group were most similar for gender, socio-economic status, IQ, and non word repetition. In the diadochokinetic tasks, the PSD group and the CCD groups were more similar. Implications for these findings in terms of clinical practice are discussed. PMID- 22059377 TI - Computational study of the reactions of methanol with the hydroperoxyl and methyl radicals. 2. Accurate thermal rate constants. AB - Multistructural canonical variational-transition-state theory with multidimensional tunneling (MS-CVT/MT) is employed to calculate thermal rate constants for the abstraction of hydrogen atoms from both positions of methanol by the hydroperoxyl and methyl radicals over the temperature range 100-3000 K. The M08-HX hybrid meta-generalized gradient approximation density functional and M08-HX with specific reaction parameters, both with the maug-cc-pVTZ basis set, were validated in part 1 of this study (Alecu, I. M.; Truhlar, D. G. J. Phys. Chem. A2011, 115, 2811) against highly accurate CCSDT(2)(Q)/CBS calculations for the energetics of these reactions, and they are used here to compute the properties of all stationary points and the energies, gradients, and Hessians of nonstationary points along each considered reaction path. The internal rotations in some of the transition states are found to be highly anharmonic and strongly coupled to each other, and they generate multiple structures (conformations) whose contributions are included in the partition function. It is shown that the previous estimates for these rate constants used to build kinetic models for the combustion of methanol, some of which were based on transition state theory calculations with one-dimensional tunneling corrections and harmonic-oscillator approximations or separable one-dimensional hindered rotor treatments of torsions, are appreciably different than the ones presently calculated using MS CVT/MT. The rate constants obtained from the best MS-CVT/MT calculations carried out in this study, in which the important effects of corner cutting due to small and large reaction path curvature are captured via a microcanonical optimized multidimensional tunneling (MUOMT) treatment, are recommended for future refinement of the kinetic model for methanol combustion. PMID- 22059378 TI - Adjacent central venous catheters can result in immediate aspiration of infused drugs during renal replacement therapy. AB - Dual-lumen haemodiafiltration catheters enable continuous renal replacement therapy in the critically ill and are often co-located with central venous catheters used to infuse drugs. The extent to which infusions are immediately aspirated by an adjacent haemodiafiltration catheter remains unknown. A bench model was constructed to evaluate this effect. A central venous catheter and a haemodiafiltration catheter were inserted into a simulated central vein and flow generated using centrifugal pumps within the simulated vein and haemodiafiltration circuit. Ink was used as a visual tracer and creatinine solution as a quantifiable tracer. Tracers were completely aspirated by the haemodiafiltration catheter unless the infusion was at least 1 cm downstream to the arterial port. No tracer was aspirated from catheters infusing at least 2 cm downstream. Orientation of side ports did not affect tracer elimination. Co location of central venous and haemodiafiltration catheters may lead to complete aspiration of infusions into the haemodiafilter with resultant drug under-dosing. PMID- 22059379 TI - APRIL and BAFF proteins increase proliferation of human adipose-derived stem cells through activation of Erk1/2 MAP kinase. AB - Human adipose-derived stem cells (hASC) are mesenchymal stem cells with reduced immunogenicity and the ability to modulate immune responses. APRIL and BAFF proteins are overexpressed in inflammatory and autoimmune diseases for which allogeneic hASC therapy is currently under clinical investigation. Modification of hASC properties by the tissue microenvironment could be a critical factor in patient outcome and is still not well understood. Our aim was to characterize the APRIL/BAFF system in hASC by analyzing the ligand and receptor expression patterns, the effects mediated by APRIL and BAFF on hASC, and the underlying signaling. We found that hASC express the tumor necrosis factor proteins APRIL (a proliferation-inducing ligand) and BAFF (B cell-activator factor) as well as their receptors TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor), BCMA (B cell maturation antigen) and the BAFF specific receptor (BAFF-R). APRIL and BAFF secretion was differentially enhanced by CXCL12 and interferon (IFN)-gamma, implicated in hASC-mediated migration and immunosuppression, respectively. In addition, APRIL and BAFF induced rapid phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and Akt kinases and promoted an increase in hASC proliferation, without affecting the immunosuppressive capacity of these cells. The use of specific chemical inhibitors indicated that the PI3K transduction pathway is involved in hASC basal growth and that APRIL- and BAFF-mediated effects are ERK-dependent. These results provide new information about the molecular mechanisms that underlie APRIL and BAFF secretion and signaling in hASC, and are of special relevance for the use of allogeneic hASC as therapeutic tools. PMID- 22059380 TI - Helminth and leech community structure in tadpoles and caudatan larvae of two amphibian species from Western Nebraska. AB - Currently no comparative studies exist on helminth and leech community structure among sympatric anuran tadpoles and salamander larvae. During June-August 2007 2009, we examined 50 bullfrog tadpoles, Rana catesbeiana , 50 barred tiger salamander larvae, Ambystoma mavortium , and 3 species of snails from Nevens Pond, Keith County, Nebraska for helminth and leech infections. The helminth and leech compound community of this larval amphibian assemblage consisted of at least 7 species, 4 in bullfrog tadpoles and 4 in barred tiger salamander larvae. Bullfrog tadpoles were infected with 2 species of nematodes ( Gyrinicola batrachiensis and Spiroxys sp.) and 2 types of metacercariae ( Telorchis sp. and echinostomatids), whereas barred tiger salamander larva were infected with 1 species of leech ( Placobdella picta ), 2 species of adult trematodes ( Telorchis corti and Halipegus sp.), and 1 species of an unidentified metacercaria. The component community of bullfrog tadpoles was dominated by helminths acquired through active penetration, or incidentally ingested through respiratory currents, or both, whereas the component community of larval salamanders was dominated by helminths acquired through ingestion of intermediate hosts (chi2 = 3,455.00, P < 0.00001). Differences in amphibian larval developmental time (2-3 yr for bullfrog tadpoles versus 2-5 mo for salamander larvae), the ephemeral nature of intermediate hosts in Nevens Pond, and the ability of bullfrog tadpole to eliminate echinostome infections had significant effects on mean helminth species richness among amphibian species and years (t = 12.31, P < 0.0001; t = 2.09, P = 0.04). Differences in herbivorous and carnivorous diet and time to metamorphosis among bullfrog tadpoles and barred tiger salamander larvae were important factors in structuring helminth communities among the larval stages of these 2 sympatric amphibian species, whereas size was important in structuring helminth and leech communities in larval salamanders, but not in bullfrog tadpoles. PMID- 22059381 TI - Coffee components inhibit amyloid formation of human islet amyloid polypeptide in vitro: possible link between coffee consumption and diabetes mellitus. AB - Global epidemic studies have suggested that coffee consumption is reversely correlated with the incidence of type 2 diabetes mellitus (T2DM), a metabolic disease. The misfolding of human islet amyloid polypeptide (hIAPP) is regarded as one of the causative factors of T2DM. Coffee extracts have three major active components: caffeine, caffeic acid (CA), and chlorogenic acid (CGA). In this study, the effects of these major coffee components, as well as dihydrocaffeic acid (DHCA) (a major metabolite of CGA and CA), on the amyloidogenicity of hIAPP were investigated by thioflavin-T based fluorescence emission, transmission electronic microscopy, circular dichroism, light-induced cross-linking, dynamic light scattering, and MTT-based cell viability assays. The results suggest that all components show varied inhibitory effects on the formation of toxic hIAPP amyloids, in which CA shows the highest potency in delaying the conformational transition of the hIAPP molecule with the most prolonged lag time, whereas caffeine shows the lowest potency. At a 5-fold excess molar ratio of compound to hIAPP, all coffee-derived compounds affect the secondary structures of incubated hIAPP as suggested by the circular dichroism spectra and CDPro deconvolution analysis. Further photoinduced cross-linking based oligomerization and dynamic light scattering studies suggested CA and CGA significantly suppressed the formation of hIAPP oligomers, whereas caffeine showed no significant effect on oligomerization. Cell protection effects were also observed for all three compounds, with the protection efficiency being greatest for CA and least for CGA. These findings suggest that the beneficial effects of coffee consumption on T2DM may be partly due to the ability of the major coffee components and metabolites to inhibit the toxic aggregation of hIAPP. PMID- 22059382 TI - Enhancement of dissolution rate and bioavailability of sulfamethoxazole by complexation with beta-cyclodextrin. AB - The purpose of this study was to improve the solubility and dissolution rate of sulfamethoxazole (SMZ) with inclusion compound of beta-cyclodextrin (beta-CD). The interaction between SMZ and beta-CD in solution was studied by the phase solubility method. The phase-solubility studies revealed the formation of inclusion complexes with poor solubility with an inclusion complex of 1:1 molar ratio and a stability constant of 122.3 M(-1). The solid complexes of SMZ with beta-CD were prepared by using kneading and coprecipitation methods. The physical mixture of these chemicals was also prepared for comparison. Inclusion complexation was confirmed by the results from the studies of infrared spectoroscopy (IR) and differential scanning calorimetry (DSC). The effect of water-soluble polymers i.e., polyethylene glycol 20000 and non-ionic surfactants i.e., polysorbate 20 on the complexation of SMZ with beta-CD was also investigated by the same methods. The rates of release of the active material from the complexes were determined from dissolution studies using USP XXII paddle method. The formulation, that provided delivery of active material near to the target value in six healthy volunteers and in vivo tests, clearly revealed that the bioavailability of active material was found to be enhanced by preparing ternary mixtures. PMID- 22059383 TI - Asymmetric introgression between the M and S forms of the malaria vector, Anopheles gambiae, maintains divergence despite extensive hybridization. AB - The suggestion that genetic divergence can arise and/or be maintained in the face of gene flow has been contentious since first proposed. This controversy and a rarity of good examples have limited our understanding of this process. Partially reproductively isolated taxa have been highlighted as offering unique opportunities for identifying the mechanisms underlying divergence with gene flow. The African malaria vector, Anopheles gambiae s.s., is widely regarded as consisting of two sympatric forms, thought by many to represent incipient species, the M and S molecular forms. However, there has been much debate about the extent of reproductive isolation between M and S, with one view positing that divergence may have arisen and is being maintained in the presence of gene flow, and the other proposing a more advanced speciation process with little realized gene flow because of low hybrid fitness. These hypotheses have been difficult to address because hybrids are typically rare (<1%). Here, we assess samples from an area of high hybridization and demonstrate that hybrids are fit and responsible for extensive introgression. Nonetheless, we show that strong divergent selection at a subset of loci combined with highly asymmetric introgression has enabled M and S to remain genetically differentiated despite extensive gene flow. We propose that the extent of reproductive isolation between M and S varies across West Africa resulting in a 'geographic mosaic of reproductive isolation'; a finding which adds further complexity to our understanding of divergence in this taxon and which has considerable implications for transgenic control strategies. PMID- 22059384 TI - Measuring healthcare disparities and racial segregation in Missouri nursing homes. AB - Measuring and, ultimately, addressing disparities in long-term care quality continue to be a challenge. Although literature suggests that disparities in healthcare quality exist and nursing homes remain relatively segregated, healthcare professionals and policymakers stand to benefit from improvements in measuring both racial segregation and healthcare disparities. This paper quantifies the relationships between healthcare disparities and racial segregation using the disparities quality index and dissimilarity index. Results suggested that the more segregated the nursing homes, the greater the observed disparities. Multivariate regression analysis indicated that the proportion of Black residents in nursing homes is the variable that best predicts disparities. PMID- 22059385 TI - Inhibition mechanism of human galectin-7 by a novel galactose-benzylphosphate inhibitor. AB - Galectins are involved in many cellular processes due to their ability to bind carbohydrates. Understanding their functions has shown the necessity for potent and specific galectin inhibitors. Human galectin-7 (hGal-7), in particular, has been highlighted as an important marker in many types of cancer by either inhibiting or promoting tumour growth. Producing ligands able to selectively target hGal-7 will offer promising tools for deciphering cancer processes in which hGal-7 is involved as well as present potential solutions for future therapeutics. Here we report the high resolution crystal structure of hGal-7 in complex with a synthetic 2-O-benzylphosphate-galactoside inhibitor (which is > 60 fold more potent than its parent galactoside). The high resolution crystallographic analysis highlights the validity of using saccharide derivatives, conserving properties of the galactose binding, while enhanced affinity and specificity is provided by the added phosphate group. This structural information will allow the design of further inhibitors with improved potency and specificity. PMID- 22059386 TI - Occupational stress amongst audiologists: compassion satisfaction, compassion fatigue, and burnout. AB - OBJECTIVE: This study aimed to investigate occupational stress amongst audiologists, along with quantification of their professional quality of life: Burnout, compassion fatigue, and compassion satisfaction. DESIGN: A cross sectional postal survey research design using an audiology occupational stress questionnaire (AOSQ), and the professional quality of life (ProQOL) instrument. STUDY SAMPLE: The sample consisted of members of the New Zealand Audiological Society. One hundred and forty-five questionnaires were mailed, 82 responses were received. RESULTS: The main findings suggest that six stress factors dominate clinical audiology: (1) time demand, (2) audiological management, (3) patient contact, (4) clinical protocol, (5) patient accountability, and (6) administration or equipment. A significant relationship was found between increasing age of the audiologist and risk of acquiring burnout (chi-square (1)=6.119, p<0.05). Pearson's correlation's revealed time demand was the strongest predictor of low compassion satisfaction (r=0.327) and burnout (r=0.463), while stress associated with patient contact was the strongest predictor of compassion fatigue (r=0.352). CONCLUSIONS: This study identifies sources of stress for clinical audiologists and different factors that contribute to professional quality of life. PMID- 22059387 TI - Fatigue in out-patients with inflammatory bowel disease is common and multifactorial. AB - BACKGROUND: Patients with inflammatory bowel disease (IBD) often complain of fatigue. AIM: To investigate the prevalence and characteristics of fatigue among IBD out-patients in Scandinavia and to provide normative values for fatigue in IBD patients. METHODS: A cross-sectional study was conducted on 425 IBD patients from six out-patient centres in Denmark, Norway and Sweden. Fatigue was measured using the Multidimensional Fatigue Inventory. The patients were also screened for anaemia and iron deficiency. Each centre included approximately 5% of their IBD cohort. The patients were enrolled consecutively from the out-patient clinics, regardless of disease activity and whether the visit was scheduled. The fatigue analysis was stratified for age and gender. RESULTS: Using the 95th percentile of the score of the general population as a cut-off, approximately 44% of the patients were fatigued. When comparing the IBD patients with disease activity to the IBD patients in remission, all dimensions of fatigue were statistically significant (P < 0.05). Being anaemic or iron deficient was not associated with increased fatigue. Being a male patient with ulcerative colitis treated with corticosteroids was a strong determinant for increased fatigue. The normative ranges for IBD fatigue were calculated. CONCLUSIONS: Fatigue in IBD is common regardless of anaemia or iron deficiency. Fatigue in IBD is most marked for patients < 60 years of age. Stratifying for gender and age is necessary when analysing fatigue, as fatigue is expressed differently between groups. PMID- 22059388 TI - Improvement of phosphoproteome analyses using FAIMS and decision tree fragmentation. application to the insulin signaling pathway in Drosophila melanogaster S2 cells. AB - This report examines the analytical benefits of high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to liquid chromatography mass spectrometry (LC-MS) for phosphoproteomics analyses. The ability of FAIMS to separate multiply charged peptide ions from chemical interferences confers a unique advantage in phosphoproteomics by enhancing the detection of low abundance phosphopeptides. LC-FAIMS-MS experiments performed on TiO(2)-enriched tryptic digests from Drosophila melanogaster provided a 50% increase in phosphopeptide identification compared to conventional LC-MS analysis. Also, FAIMS can be used to select different population of multiply charged phosphopeptide ions prior to their activation with either collision activated dissociation (CAD) or electron transfer dissociation (ETD). Importantly, FAIMS enabled the resolution of coeluting phosphoisomers of different abundances to facilitate their unambiguous identification using conventional database search engines. The benefits of FAIMS in large-scale phosphoproteomics of D. melanogaster are further investigated using label-free quantitation to identify differentially regulated phosphoproteins in response to insulin stimulation. PMID- 22059389 TI - Control of Ostwald ripening by using surfactants with high surface modulus. AB - We describe results from systematic measurements of the rate of bubble Ostwald ripening in foams with air volume fraction of 90%. Several surfactant systems, with high and low surface modulus, were used to clarify the effect of the surfactant adsorption layer on the gas permeability across the foam films. In one series of experiments, glycerol was added to the foaming solutions to clarify how changes in the composition of the aqueous phase affect the rate of bubble coarsening. The experimental results are interpreted by a new theoretical model, which allowed us to determine the overall gas permeability of the foam films in the systems studied, and to decompose the film permeability into contributions coming from the surfactant adsorption layers and from the aqueous core of the films. For verification of the theoretical model, the gas permeability determined from the experiments with bulk foams are compared with values, determined in an independent set of measurements with the diminishing bubble method (single bubble attached at large air-water interface) and reasonably good agreement between the results obtained by the two methods is found. The analysis of the experimental data showed that the rate of bubble Ostwald ripening in the studied foams depends on (1) type of used surfactant-surfactants with high surface modulus lead to much slower rate of Ostwald ripening, which is explained by the reduced gas permeability of the adsorption layers in these systems; (2) presence of glycerol which reduces the gas solubility and diffusivity in the aqueous core of the foam film (without affecting the permeability of the adsorption layers), thus also leading to slower Ostwald ripening. Direct measurements showed that the foam films in the studied systems had very similar thicknesses, thus ruling out the possible explanation that the observed differences in the Ostwald ripening are due to different film thicknesses. Experiments with the Langmuir trough were used to demonstrate that the possible differences in the surface tensions of the shrinking and expanding bubbles in a given foam are too small to strongly affect the rate of Ostwald ripening in the specific systems studied here, despite the fact that some of the surfactant solutions have rather high surface modulus. The main reason for the latter observation is that the rate of surface deformation of the coarsening bubbles is extremely low, on the order of 10(-4) s(-1), so that the relaxation of the surface tension (though also slow for the high surface modulus systems) is still able to reduce the surface tension variations down to several mN/m. Thus, we conclude that the main reason for the reduced rate of bubble Ostwald ripening in the systems with high surface modulus is the low solubility and diffusivity of the gas molecules in the respective condensed adsorption layers (which have solid rather than fluid molecular packing). PMID- 22059390 TI - Aspiration thrombectomy during primary percutaneous coronary intervention as adjunctive therapy to early (in-ambulance) abciximab administration in patients with acute ST elevation myocardial infarction: an analysis from Leiden MISSION! acute myocardial infarction treatment optimization program. AB - BACKGROUND: The benefits of early abciximab administration and thrombus aspiration in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI) have previously been elaborated. However, whether there is an adjunctive effect of thrombus aspiration among STEMI patients, with angiographic evidence of thrombus, receiving early prehospital abciximab remains unclear. METHODS: In the context of a fixed protocol for PPCI, 158 consecutive patients with STEMI were enrolled, in whom abciximab was started early before hospital arrival (in-ambulance); 79 patients who had PPCI with thrombus aspiration (thrombectomy-facilitated PCI group), were compared to 79 who had PPCI without thrombus aspiration (conventional PCI group) in a prospective nonrandomized study. The primary end-point was complete ST segment resolution within 90 minutes. Secondary end points included distal embolization, enzymatic infarct size as well as left ventricular ejection fraction (LVEF) assessed by gated single-photon emission computed tomography. Major adverse cardiac events (MACEs) were evaluated up to 12 months. RESULTS: Both groups were comparable for baseline characteristics. ST-segment resolution was significantly higher in the thrombectomy-facilitated group (P = 0.002), and multivariate analysis identified thrombectomy as an independent predictor of ST segment resolution (OR = 9.4, 95% CI = 2.6-33.5, P = 0.001). Distal embolization was higher in the conventional PCI group among patients with higher thrombus grades. No difference was observed between both groups in infarct size assessed by peak creatine kinase (p = 0.689) and peak Tn-T levels (P = 0.435). Also, the LVEF at 3 months was similar (P = 0.957). At 12 month clinical follow-up, thrombus aspiration was, however, associated with reduced all-cause mortality (log-rank p = 0.032). CONCLUSION: Among STEMI patients treated with PPCI and in ambulance abciximab, it appears that a selective strategy of thrombus aspiration still has additive benefit. PMID- 22059391 TI - Low prevalence of Helicobacter pylori-negative gastric cancer among Japanese. AB - BACKGROUND AND AIMS: The true prevalence of Helicobacter pylori-negative gastric cancer (HpNGC) is unknown. We attempt to clarify the prevalence and clinicopathologic features of HpNGC in Japanese. METHODS: Helicobacter pylori infection was detected by antibody titer and microscopic observation. In addition, we confirmed the lack of endoscopic atrophy and histologic gastritis. In these cases, we added urea breath test or rapid urease test to confirm the absence of H. pylori. The mucus phenotype of gastric cancer tissue was also evaluated by immunohistochemistry. RESULTS: We screened 3161 gastric cancer cases from 1996 to 2010, and 21 cases were regarded as H. pylori negative. Clinically, patients with HpNGC were younger than patients with H. pylori-positive gastric cancer (controls), and revealed a lack of male dominancy. Histologically, diffuse type was frequently found. All patients examined were pepsinogen negative. Among HpNGC cases with endoscopic resection, the depressed macroscopic appearance was dominant. The prevalence of HpNGC was calculated as 0.66% (95% confidence interval = 0.41-1.01). The mucus phenotype of HpNGC was similar to that of the controls. CONCLUSION: The prevalence of HpNGC is very low and its pathological characteristics are different from common gastric cancer. PMID- 22059392 TI - Randomized trial on 14 versus 7 days of esomeprazole, moxifloxacin, and amoxicillin for second-line or rescue treatment of Helicobacter pylori infection. AB - BACKGROUND: Triple therapy with a proton pump inhibitor, moxifloxacin, and amoxicillin has been proven effective in first-line treatment of Helicobacter pylori infection. AIM: To explore 1, the value of triple therapy with esomeprazole, moxifloxacin, and amoxicillin in second-line or rescue treatment of Caucasian patients and 2, the impact of treatment duration on eradication success. METHODS: H. pylori-infected patients with at least one previous treatment failure were randomized to oral esomeprazole 20 mg b.i.d., moxifloxacin 400 mg o.d., and amoxicillin 1000 mg b.i.d. for either 7 (EMA-7) or 14 days (EMA 14). Eradication was confirmed by 13C urea breath test. Antimicrobial susceptibility testing was performed in all patients at baseline and in patients who failed treatment. RESULTS: Eighty patients were randomized, and 60% had >= 2 previous treatment failures. Pretreatment resistance against clarithromycin and metronidazole was found in 70.5 and 61.5% of cases, respectively. The intention to-treat eradication rate was significantly higher after EMA-14 compared with EMA 7 (95.0 vs 78.9%, p = .036). No independent risk factor for treatment failure could be identified. There were no serious adverse events. Five of the EMA-14 patients (12.5%) compared with none of the EMA-7 patients discontinued prematurely because of adverse events (p = .031). Post-treatment resistance against moxifloxacin was found in one of seven patients with isolated organisms (14.3%). CONCLUSION: Second-line/rescue H. pylori eradication therapy with esomeprazole, moxifloxacin, and amoxicillin is very effective and well tolerated. Fourteen days of treatment significantly increase the eradication rate but also the rate of adverse events. PMID- 22059393 TI - Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status. AB - BACKGROUND: The clinical significance of Helicobacter pylori antibody titer has been controversial, and the association between the extent of gastric atrophy or acid secretion and H. pylori antibody concentration has not been elucidated. MATERIALS AND METHODS: Serum pepsinogen, H. pylori antibody concentration, and fasting gastric pH (as an indicator of acid secretion) were measured in 231 patients undergoing upper gastrointestinal endoscopy. "Atrophic" pepsinogen was defined as pepsinogen-I < 70 ng/mL and pepsinogen-I/II ratio < 3. Other levels of pepsinogen were defined as "normal". Fasting gastric pH was analyzed in subjects stratified by pepsinogen level and by H. pylori antibody concentration. RESULTS: Helicobacter pylori antibody concentration showed no significant relationship with fasting gastric pH when all subjects were analyzed together. In H. pylori seronegative subjects, fasting gastric pH was within the normal range, irrespective of the extent of mucosal atrophy. In H. pylori-seropositive subjects, H. pylori antibody concentration was positively correlated with fasting gastric pH in subjects with "normal" pepsinogen, but inversely correlated in those with "atrophic" pepsinogen. Particularly in subjects with low H. pylori antibody concentration and atrophic mucosa, a group reportedly at high risk of noncardia cancer, the most impaired acid secretion was shown among subjects with atrophic mucosa. CONCLUSIONS: The relationship between acid secretion and H. pylori antibody concentration differs depending on the presence of mucosal atrophy. Our findings provide a possible rationalization for measuring both serum pepsinogen levels and H. pylori antibody concentration in gastric cancer screening. PMID- 22059394 TI - Antibacterial effects of the urushiol component in the sap of the lacquer tree (Rhus verniciflua Stokes) on Helicobacter pylori. AB - BACKGROUND: Urushiol is a major component of the lacquer tree which has been used as a folk remedy for the relief of abdominal discomfort in Korea. The aim of this study was to evaluate the antibacterial effects of the urushiol on Helicobacter pylori. MATERIALS AND METHODS: Monomer and 2-4 polymer urushiol were used. In the in vitro study, pH- and concentration-dependent antibacterial activity of the urushiol against H. pylori were investigated. In addition, the serial morphological effects of urushiol on H. pylori were examined by electron microscopy. In vivo animal study was performed for the safety, eradication rate, and the effect on gastritis of urushiol. The expression of pro-inflammatory cytokines was checked. RESULTS: All strains survived within a pH 6.0-9.0. The minimal inhibitory concentrations of the extract against strains ranged 0.064 0.256 mg/mL. Urushiol caused separation of the membrane and lysis of H. pylori within 10 minutes. Urushiol (0.128 mg/mL * 7 days) did not cause complications on mice. The eradication rates were 33% in the urushiol monotherapy, 75% in the triple therapy (omeprazole + clarithromycin + metronidazole), and 100% in the urushiol + triple therapy, respectively. H. pylori-induced gastritis was not changed by urushiol but reduced by eradication. Only the expression of interleukin-1beta in the gastric tissue was significantly increased by H. pylori infection and reduced by the urushiol and H. pylori eradication (p = .014). CONCLUSIONS: The urushiol has an antibacterial effect against H. pylori infection and can be used safely for H. pylori eradication in a mouse model. PMID- 22059395 TI - Histopathology of gastric erosions. Association with etiological factors and chronicity. AB - BACKGROUND: The histopathologic characteristics of the antral erosions, and a comparison with samples systematically collected from the background antral mucosa, have not been studied previously. Similarly, unknown is the association of these features with suspected etiological factors and chronicity of erosion. MATERIAL AND METHODS: We studied 117 patients with gastric erosions in the absence of peptic ulcer disease. With 28 patients available for a follow-up 19 years later, sites of erosions and background mucosa were biopsied and histopathology of both independently assessed at both visits. Helicobacter pylori status was examined from the biopsies taken in the initial and follow-up gastroscopies. Only subjects originally displaying antral erosions were included. The presence of Herpes simplex virus (HSV) antibodies was analyzed and use of nonsteroidal anti-inflammatory drug (NSAID) was inquired. RESULTS: Initially, the inflammation was more active in the region of erosions than elsewhere in antral mucosa. More active inflammation in the erosion was associated with HSV seropositivity, Helicobacter pylori infection, and the recent use of NSAIDs. In the follow-up visit, antral erosions were present in 38% (3/8) of Helicobacter pylori negatives and in 35% (7/20) of positives (p = ns). The Helicobacter pylori positive subjects with chronic or recurrent erosions had initially higher scores of neutrophils compared to subjects with nonrecurrent or nonchronic erosions (2.7 +/- 0.5 vs 1.2 +/- 1.0; p = .002). CONCLUSIONS: Focally enhanced inflammation is characteristic for gastric erosions. This focal inflammation was associated with HSV seropositivity or NSAID use suggesting that such inflammation may be important in the pathogenesis of gastric antral erosions. Highly active inflammation in the erosions associates with their chronicity. PMID- 22059396 TI - Protease-activated receptor-2 (PAR2) in human gastric mucosa as mediator of proinflammatory effects in Helicobacter pylori infection. AB - INTRODUCTION: Protease-activated receptors (PAR) are seven transmembrane receptors that are expressed throughout the gastrointestinal tract. In vitro experiments using gastric tumor cell lines, murine models and one clinical study provided evidence for a potential role of PAR2 in Helicobacter pylori-induced gastritis. AIM: To investigate PAR2 expression in H. pylori-infected patients and correlation with proinflammatory IL-8, IL-1beta as well as histologic changes of the mucosa. Furthermore, PAR2 expression was studied in context to mucosal amounts of secretory leukocyte protease inhibitor (SLPI), a putative regulator of PAR2. METHODS: Twenty-two H. pylori-infected patients and 72 H. pylori-negative subjects underwent upper GI endoscopy. In antrum-derived mucosal biopsies, PAR2, IL-1beta, IL-8, and SLPI expression was analyzed by quantitative RT-PCR, and in part by ELISA and immunohistochemistry. Histopathologic evaluation of gastritis was performed according to the updated Sydney classification. RESULTS: IL-8 gene expression was 5-fold increased in the mucosa of H. pylori-infected patients compared with non-infected (p < .0001), whereas no differences for PAR2 and IL 1beta mRNA amounts were observed between both groups. PAR2 gene expression correlated positively with transcript levels of IL-8, IL-1beta as well mucosal SLPI levels in H. pylori-infected patients (r: 0.47-0.84; p < .0001), whereas no correlation was found with the degree of gastritis. CONCLUSIONS: PAR2 represents an additive pathway of IL-8 secretion and proinflammatory effects in H. pylori induced gastritis. Reduced SLPI levels leading to higher serine protease activities in the mucosa of infected subjects might regulate PAR2 activation. PMID- 22059397 TI - Characterization and functional activity of murine monoclonal antibodies specific for alpha1,6-glucan chain of Helicobacter pylori lipopolysaccharide. AB - BACKGROUND: The outer core region of H. pylori lipopolysaccharide (LPS) contains alpha1,6-glucan previously shown to contribute to colonizing efficiency of a mouse stomach. The aim of the present study was to generate monoclonal antibodies (mAbs) specific for alpha1,6-glucan and characterize their binding properties and functional activity. MATERIALS AND METHODS: BALB/c mice were injected intraperitoneally with 10(8) formalin-fixed H. pylori O:3 0826::Kan cells 3* over 56 days to achieve significant titer. Anti-alpha1,6-glucan-producing hybridomas were screened by indirect ELISA using purified H. pylori O:3 0826::Kan LPS. One clone, 1C4F9, was selected for further characterization. The specificities of mAbs were determined by indirect and inhibition ELISA using structurally defined H. pylori LPS and synthetic oligosaccharides, and whole-cell indirect ELISA (WCE) of clinical isolates. They were further characterized by indirect immunofluorescent (IF) microscopy and their functional activity in vitro determined by serum bactericidal assays against wild-type and mutant strains of H. pylori. RESULTS: The generated anti-alpha1,6-glucan IgM, 1C4F9, has demonstrated an excellent specificity for the glucan chain containing 5 to 6 alpha1,6-linked glucose residues and showed surface accessibility by IF microscopy with H. pylori cells adherent to gastric adenocarcinoma cells monolayers. Of 38 isolates from Chile, 17 strains reacted with antiglucan mAbs in WCE (OD450 >= 0.2). Bactericidal activity was observed against selective wild type and mutant H. pylori strains exhibiting OD450 values of >= 0.45 in WCE. CONCLUSIONS: Anti-alpha1,6-glucan mAbs could have potential application in typing and surveillance of H. pylori isolates as well as offer insights into structural requirements for the development of LPS-based vaccine against H. pylori infections. PMID- 22059398 TI - First-time urea breath tests performed at home by 36,629 patients: a study of Helicobacter pylori prevalence in primary care. AB - BACKGROUND: The aim of the current study was (1) to describe the use of a (13) C urea breath test (UBT) that was performed by patients at their homes as a part of a test-and-treat strategy in primary care and (2) to investigate the prevalence of Helicobacter pylori in patients taking a first-time UBT. MATERIAL AND METHODS: The patients performed UBTs at home based on the discretion of the general practitioner and mailed the breath bags to a central laboratory for analysis. Each patient was identified by a unique civil registration number. The study was population-based, and the background population was approximately 700,000 people. RESULTS: From 2003 to 2009, 44,487 UBTs were performed. Of these, 36,629 were first-time UBTs. In total, 726 of 45,213 breath bags received (1.6%) were unable to be analyzed because of errors with the bags. For both women and men who were <= 45 years of age, positive H. pylori declined over the time course of the study (women: 19.6% in 2003 to 17.6% in 2009, p < .01; men: 20.7% in 2003 to 16.9% in 2009, p < .001). Patients who were older than 45 years had significantly higher positive H. pylori results than younger patients. CONCLUSIONS: A test-and-treat system was possible to implement that allowed patients to perform UBTs at their homes. The results of the first-time UBTs demonstrated that approximately one of five patients who presented with dyspepsia in the clinical setting of Danish primary care was infected with H. pylori. PMID- 22059399 TI - Genotypic and phenotypic variation of Lewis antigen expression in geographically diverse Helicobacter pylori isolates. AB - BACKGROUND: Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. MATERIALS AND METHODS: From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and beta (1,3)galT loci in 113 H. pylori strains. RESULTS: Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le(a) and Le(b) ) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). CONCLUSION: These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression. PMID- 22059401 TI - The relationship of muscle fibre size to tenderness of beef. AB - Steaks were removed from loins of beef carcasses at 1, 3, 6 or 14 days post mortem for fragmentation index (MFI), Warner-Bratzler Shear Force (SF) and sensory panel tenderness evaluation. Also, after 1 day of storage, samples were removed for histological observations. Greatest improvement in tenderness, SF and MFI occurred within the first 6 days of storage. Sensory panel tenderness was correlated (P < 0.01) with SF and MFI. Average muscle fibre size was correlated (P < 0.01) with tenderness and SF at days 1 and 3, but not at days 6 and 14. Evidently, muscle fibre size is important to tenderness prior to post-mortem storage of meat and proteolysis, but becomes less of a factor in tenderness after 6 days of storage. PMID- 22059402 TI - Some parameters involved in production of Zousoon-A semi-dry, long fibered pork product. AB - The production of Zousoon, which is a semi-dry, long-fibered (5-8 cm) pork product, is described as traditionally produced in Taiwan. The production process is an empirical one and is more of an art than a science. The present paper describes a modified clothes dryer developed to tumble and dry the product, which was shown to result in improved heat transfer and greater shear forces that gave better control of evaporation of water while causing the muscle bundles to disintegrate into smaller subunits. Color development and finishing to a final a(w) of 0.60 to 0.65 for the predried product was found to be best achieved by heating with steam at 150 degrees C for 7 min. The predried product was finished in a steam-heated dryer-finisher while adding fat. The final product had a yellowish-brown color and a fibrous appearance, being more uniform in color and texture than that produced in the traditional gas-fired, scraping-frypan. PMID- 22059403 TI - Use of perfused isolated muscle, as studied by (31)P NMR, to investigate metabolism and post-mortem changes. AB - An experimental system was designed to study as independently as possible the effects of various in-vivo or post-mortem factors susceptible to influence muscle metabolism. This system was made up of an NMR probe, a physiological stimulator, a perfusion system and a force monitoring device. Rabbit muscles were isolated and perfused with bovine red cells, then put into the NMR probe to follow the evolution of pH and phosphorylated compounds. It was possible to keep muscle metabolism stable for 2 h. Death was simulated by stopping the perfusion which allowed post-mortem changes to be followed. The effects of adrenaline perfusion or of a 5 s tetanus on some traits of metabolism and on changes following muscle death were studied. Tetanus immediately before perfusion was stopped accelerated changes in pH and in phosphocreatine and ATP contents; adrenaline perfusion during 30 min before perfusion was stopped had little effect on these traits. PMID- 22059404 TI - A comparison of some muscle metabolites in stress susceptible and resistant Landrace gilts after halothane exposure or exercise stress. AB - Sixty-six South African Landrace gilts were used in the experiments. At the age of 21 weeks, 47 of the pigs were challenged with halothane exposure. As a result 17 of the pigs died, and were classified stress susceptible (SS), whereas the 30 survivors were classified stress resistant (SR). The other 19 pigs were subjected to treadmill exercise. Four of the exercised pigs died. The pigs that survived the treadmill exercise were later exposed to halothane. The pigs that died as a result of the halothane exposure (n = 5) or the treadmill exercise (n = 4), were classified SS (n = 9) and the survivors as SR (n = 10). A biopsy of the M. semitendinosus was used for measurement of difference in muscle lactate, ATP, glucose 6-phosphate, phosphocreatine, glucose and glycogen concentrations. The results show that in all pigs exercise resulted in the higher stimulation of glycogenolysis than did halothane exposure. However, SS pigs overall showed a greater stimulation of glycogenolysis and glycolysis and general anaerobic metabolism, compared to SR pigs. Under halothane exposure, glycogenolysis and anaerobic metabolism were stimulated in the SS pigs to a much greater extent than in SR pigs, with significant differences between all the muscle metabolites determined. However, treadmill exercise, although sufficient to cause death in some pigs, resulted only in significantly higher lactate and glucose 6-phosphate concentrations. SR pigs exposed to halothane had significantly higher ATP, phosphocreatine and glycogen concentrations, but a lower glucose concentration than exercised SR pigs, indicating less severe stimulation of glycogenolysis by halothane than exercise. No significant differences were found in the determined muscle metabolites in SS pigs exposed to halothane compared to exercised SS pigs. In conclusion, these differences suggest that different mechanisms of stimulation of metabolism on exposure to halothane and exercise may exist, although both types of stress cause stimulation of glycogenolysis. PMID- 22059405 TI - An HPLC method using FMOC-ADAM for determination of hydroxyproline in muscle. AB - An HPLC method using 9-fluorenylmethyl chloroformate-1-amino-adamantane (FMOC ADAM) for the determination of hydroxyproline (HYP) in muscle hydrolyzates is described. The HYP was converted to a stable fluorescent derivative with FMOC after removal of all primary amino acids with ortho-phthaldialdehyde and 2 mercaptoethanol. Excess FMOC was reacted with a hydrophobic amine, ADAM, thus eliminating the need for pentane or diethyl ether extraction. The method was performed without the use of controlled temperature derivatizations or extra equipment (e.g. column switching valves). Analysis of HYP was complete after 3 min, with a total analysis time of 7.5 min. The HYP content of various muscle samples obtained with the HPLC procedure compared very well with values obtained using a colorimetric assay. PMID- 22059406 TI - Differentiation of closely related species by DNA hybridization. AB - The specificity of genomic DNA probes for species differentiation by slot blot hybridization has been investigated. Experiments have been performed investigating species differentiation between monkey and human and between cattle, goat and sheep. It is demonstrated that cross hybridization between probe and DNA sequences from closely related species is reduced by addition of unlabelled DNA from the cross hybridizing species. Quantitative species differentiation is shown possible for all species although with different detection limits. For differentiation between cattle and sheep or goat the detection limits are determined to less than 0.01% whereas the detection limits for differentiation between the closely related species sheep and goat are about 10%. PMID- 22059407 TI - Study of proteolysis during the processing of a dry fermented pork sausage. AB - Dry pork sausage was formulated, fermented and dried for 41 days. Gross composition was determined and proteolysis was monitored by assaying the following N fractions: water-soluble nitrogen (WSN), salt-soluble nitrogen (SSN), ultrafiltration (UF) permeates of WSN and SSN, phosphotungstic acid (PTA)-soluble and -insoluble fractions and free amino acids. Meat and sausages, water- and salt insoluble components, UF-retentates of WSN and SSN were assessed by SDS-PAGE at different stages of ripening. The amount of WSN, WSN permeate, PTA-soluble N and free amino acids increased during processing, while the SSN and PTA-insoluble N decreased. The electrophoretic studies demonstrated that proteolysis of the heavy myosin chain, alpha-actinin and actin was most prominent. The increased insolubility of meat proteins was confirmed by SDS-PAGE. PMID- 22059409 TI - A randomised controlled trial of probiotics for the prevention of spontaneous preterm delivery associated with bacterial vaginosis: preliminary results. AB - BACKGROUND: Bacterial vaginosis increases the risk of spontaneous preterm delivery at less than 34 weeks of gestation. OBJECTIVE: The purpose of this study was to evaluate the efficacy of the early administration of selected lactobacilli strains (probiotics) to pregnant women with asymptomatic bacterial vaginosis/intermediate-degree infections to prevent spontaneous premature delivery and associated neonatal morbidity. METHODS/DESIGN: Asymptomatic pregnant women at less than 20 weeks of gestation, with no indication of elective preterm delivery, with a vaginal pH >= 4.5 and Nugent score > 3 were randomly assigned to the placebo or intervention group (oral administration of selected lactobacilli up to the 24th to 26th week of gestation). The randomisation was stratified for the history of premature delivery (HPD) and blocked. The allocation was concealed, and the participating health professionals and patients were blinded. The primary outcome was preterm delivery (<34 to <32 weeks), and the secondary outcomes were associated neonatal complications. RESULTS: In total, 4,204 pregnant women were screened; 320 and 324 individuals were respectively randomly assigned to the placebo and intervention groups, and 62% finished the trial. None of the randomised patients were lost to follow-up. For the non-HPD stratum, the intent-to-treat relative risks of spontaneous premature birth at < 34 and < 37 weeks' gestation were 0.33 (0.03, 3.16) and 0.49 (0.17, 1.44), respectively, and they were non-significant (ns) with p = 0.31 and 0.14. The corresponding actual treatment figures were zero and 0.32 (0.09, 1.19), which were ns with p = 0.12 and 0.06. The intent-to-treat relative risk of spontaneous premature birth at < 37 weeks of gestation for the trial as a whole, including HPD and non-HPD participants, was 0.69 (0.26, 1.78), p = 0.30 (ns). The neonatal complications under evaluation occurred in only one infant (< 34 weeks; placebo group) who presented with respiratory distress syndrome and suspected early neonatal sepsis. The recorded adverse events were minor and relatively non-specific. CONCLUSIONS: The efficacy of the tested probiotics to prevent preterm delivery among women without a history of preterm delivery was not determined because the study sample was insufficient to estimate statistically significant intent-to-treat effects; additional studies are needed to evaluate this intervention among these women. TRIAL REGISTRATION: Trial registration at NIH register: NCT00303082. Sources of funding: the Brazilian Health Ministry and the State of Rio de Janeiro Research Foundation. PMID- 22059410 TI - Effects of feed treatment and gender on the flavour and texture profiles of cured and uncured pork cuts. I. Ractopamine treatment and dietary protein level. AB - Equal numbers of barrows (64) and gilts (64) were randomly allocated to two separate diets containing 17.6 and 19.6% crude protein. Subsequently within each gender/diet treatment group, pigs were equally and randomly assigned to two ractopamine treatment groups (i.e. 0 or 20 ppm ractopamine), resulting in 16 pigs per gender/diet/ractopamine subgroup. The feeding trial lasted an average of 41 days, and the pigs went on trial at an average weight of 64.5 kg and were slaughtered at an average weight of 98.2 kg. Five barrows and five gilts were subsampled at random from each gender/diet/ractopamine subgroup for palatability evaluations. Comprehensive palatability evaluations were conducted on both cured and uncured pork cuts. Results revealed no meaningful differences in flavour, texture, or cooking properties attributable to dietary protein level (17.6 vs 19.6% crude protein) or to ractopamine. Thus, within the context of conditions employed in the present study, ractopamine can be administered with different dietary crude protein levels to improve production efficiency and carcass composition, without influencing palatability and cooking properties or consumer acceptance. Gender effects have been reported elsewhere (Jeremiah et al., 1994). PMID- 22059411 TI - Effects of feed treatment and gender on the flavour and texture profiles of cured and uncured pork cuts. II. Ractopamine treatment and dietary protein source. AB - A total of 128 barrows and 128 gilts were equally and randomly allocated to two separate barley-based diets containing two distinct protein sources (soybean meal and canola meal). Subsequently, the pigs within each gender/ diet treatment subgroup were equally and randomly assigned to two ractopamine treatment groups (0 or 20 ppm). The feeding trial lasted an average of 42 days. The pigs went on trial at an average weight of 67.9 kg and were slaughtered at an average weight of 101.9 kg. Ten pigs selected at random from each gender/diet/ractopamine subgroup were utilized for detailed palatability evaluation. These comprehensive palatability evaluations were conducted on both cured and uncured pork cuts. Results revealed no differences of practical importance in flavour, texture, or cooking properties attributable to dietary protein source or to administration of ractopamine, despite the fact a few statistically significant differences were observed. Thus, ractopamine can be administered with different dietary protein sources to improve production efficiency and improve carcass composition, without influencing palatability and cooking properties, or consumer acceptance. Gender effects have been reported elsewhere (Jeremiah et al., 1994b). PMID- 22059412 TI - The effects of feed treatment and gender on the flavour and texture profiles of cured and uncured pork cuts. III. Effects of gender. AB - A total of 384 pigs (192 barrows and 192 gilts) was utilized to evaluate the effects of gender on the flavour and texture profiles of cured and uncured pork cuts. Observed differences in all cuts indicated the incidence, intensity, and/or order of appearance of flavour character notes were more appropriate, in samples from barrows than in samples from gilts; differences observed in all cuts also indicated textural properties were more appropriate, in samples from barrows than in samples from gilts. However, the magnitude of such differences in all cuts, was insufficient to influence flavour and texture amplitude ratings. Consequently, even though cuts from barrows are marginally superior to cuts from gilts in both flavour and texture, this superiority is unlikely to be of practical importance. The effects of ractopamine treatment and protein level (Jeremiah et al., 1994a) and ractopamine treatment and protein source (Jeremiah et al., 1994b) have been previously covered. PMID- 22059413 TI - Kinetic studies of the effect of muscle fiber type and tripolyphosphate on the aggregation of porcine salt-soluble proteins. AB - The kinetics of thermal aggregation of salt-soluble proteins (SSP) isolated from porcine Longissimus dorsi (75% white fiber, Serratus ventralis (43% red fiber, and Vastus intermedius (76% red fiber) muscles were studied in the presence of sodium tripolyphosphate (TPP). SSP solutions containing 0-2.0% TPP were heated at constant temperatures between 40 degrees and 70 degrees C, and protein aggregation was monitored using turbidity measurements. SSP aggregation followed first-order kinetics, and the rate and extent of aggregation increased with the red fiber content. Addition of TPP generally increased the aggregation temperature for both white and red muscle SSP, but the changes in the aggregation rate varied depending on the specific temperature and muscle type. Arrhenius plots revealed 10.2-11.5% reduction in the activation energy for SSP aggregation caused by 0.5% TPP. These results indicate that SSPs from red and white muscle types differ in thermal properties and response to phosphate treatments. PMID- 22059414 TI - The molecular location of Ehrlich chromogen and pyridinoline cross-links in bovine perimysial collagen. AB - Collagenous peptides containing the Ehrlich chromogen (EC), a trifunctional cross link of proposed pyrrolic structure, were selectively isolated from a tryptic digest of bovine perimysial collagen by coupling to a diazotised support. Peptides containing pyridinoline (Pyr), another trifunctional cross-link but based on a 3-hydroxypyridinium ring, were isolated from the uncoupled material. The isolated cross-linked peptides were purified by chromatographic procedures and subsequently characterised by amino acid and sequence analyses. EC occurred in stoichiometric amounts in three-chained peptides derived from type I collagen cross-link regions. In contrast, Pyr was found in non-stoichiometric amounts in three-chained peptides where two of the chains were identified as the 76 amino terminal residues of the alpha1 (III) collagen chain. The third chain in these Pyr cross-linked peptides was derived from the C-terminal helical cross-link region of either type III collagen or the corresponding region of type I collagen, with the former region predominating. These findings suggest that EC and Pyr cross-links of perimysial collagen are associated mainly with type I and type III collagen respectively. PMID- 22059415 TI - Shelf-life of vacuum-packaged wild boar meat in relation to that of vacuum packaged pork: Relevance of intrinsic factors. AB - In order to study the factors influencing the relatively poor keepability of pork compared with beef, a study with wild boar meat was carried out. Microbiological and sensory quality traits of vacuum-stored wild boar (Sus scrofa scrofa) cuts of M. longissimus dorsi (longissimus) at 0 degrees C were determined after 1, 10, 28, 42, 56, 70, 84 and 98 days and of tenderloins after 3, 35, 49 and 63 days. The amount of glycogen, glucose and glucose-6-phosphate in the longissimus cuts was measured during storage, in order to study the processes that determine shelf life. Tenderloins developed off-odours after 35 days, probably due to Enterobacteriaceae growth. Unacceptable discolouration of longissimus cuts and off-odour development were noticed after 84-98 days. Shelf-life comparison between wild boar meat and pork stored under similar conditions indicates that the relatively poor keepability of pork is due to intrinsic factors. Glucose depletion is probably triggering the onset of spoilage processes. PMID- 22059416 TI - Observations on some chemical and physical characteristics of buffalo meat. AB - Proximate composition, sarcoplasmic and myofibrillar protein fractions of buffalo meat were similar to those of beef. Buffalo meat was also rich in lysine. Meat from young animals had a lower collagen content than that from old ones. As the temperature of holding the carcasses was increased, the rate of pH fall was faster. Meat from stressed animals showed a higher ultimate pH. Percentage of cooking loss and thermal shrinkage was higher in muscles of old animals than in young ones, which probably reflected the poor condition of the older animals. Meat cooked by pressure cooking showed lower Warner-Bratzler shear values as compared with meat cooked in boiling water. PMID- 22059417 TI - The influence of low temperature, type of muscle and electrical stimulation on the course of rigor mortis, ageing and tenderness of beef muscles. AB - The course of rigor mortis, ageing and tenderness have been evaluated for two beef muscles, M. semimembranosus (SM) and M. longissimus dorsi (LD), when entering rigor at constant temperatures in the cold-shortening region (1, 4, 7 and 10 degrees C). The influence of electrical stimulation (ES) was also examined. Post-mortem changes were registered by shortening and isometric tension and by following the decline of pH, ATP and creatine phosphate. The effect of ageing on tenderness was recorded by measuring shear-force (2, 8 and 15 days post mortem) and the sensory properties were assessed 15 days post mortem. It was found that shortening increased with decreasing temperature, resulting in decreased tenderness. Tenderness for LD, but not for SM, was improved by ES at 1 and 4 degrees C, whereas ES did not give rise to any decrease in the degree of shortening during rigor mortis development. This suggests that ES influences tenderization more than it prevents cold-shortening. The samples with a pre-rigor mortis temperature of 1 degrees C could not be tenderized, when stored up to 15 days, whereas this was the case for the muscles entering rigor mortis at the other higher temperatures. The results show that under the conditions used in this study, the course of rigor mortis is more important for the ultimate tenderness than the course of ageing. PMID- 22059418 TI - The effect of high post-mortem temperature on the development of pale, soft and exudative pork: Interaction with ultimate pH. AB - The effects of post-mortem temperature and ultimate pH (pH(u), 24 h post mortem) on the development of the pale, soft and exudative (PSE) characteristics in pig longissimus dorsi muscle were studied. Ten out of the 13 pigs used received pre slaughter injections of adrenaline in order to deplete muscle glycogen stores. The two muscles from each pig were held at 12 or 35 degrees C during rigor mortis development. Results from covariance analysis, using pH(u) as covariate, showed that a high temperature (35 degrees C) resulted in a dramatic increase in internal light scattering (FOP) 24 h post mortem and a significant decrease in water- and salt-soluble proteins. Cooking loss, sarcomere length and drip loss did not vary significantly with rigor temperature. Interaction between temperature and pH(u) was estimated by assessing the relationship between pH(u) and the difference between the two rigor temperatures for selected traits. The best predictive model was a segmented quadratic model with a plateau which gave significant results for FOP, drip loss, water- and salt-soluble proteins. The effect of temperature decreased curvilinearly when pH increased until a constant value above which no noticeable difference was recorded (drip loss, water- and salt-soluble proteins) or a constant difference was reached (FOP). The pH values corresponding to the convergence points differed from one trait to another. They ranged from 5.72 to 6.22. These results illustrate the importance of muscle glycogen content at slaughter and subsequent pH(u) with regard to the development of temperature-induced PSE meat. PMID- 22059419 TI - Fatty acid composition of the meat and fat of the one-humped camel (camelus dromedarius). AB - The fatty acid composition of lean raw meat taken from the hind leg of seven young (1-3 years of age) male one-humped camels (Camelus dromedarius) has been determined by capillary gas-liquid chromatography; fat samples taken from the hump of these seven camels were also analysed. The saturated fatty acids in the meat account for 51.5% of the total fatty acids, while the monosaturated and polyunsaturated chains constitute 29.9 and 18.6%, respectively. The major fatty acids in camel meat are palmitic (26.0%), oleic (18.9%) and linoleic (12.1%), with smaller amounts of other fatty acids, both normal and branched, that range in chain lengths from C(14) to C(22). The fatty acids of dromedary fat are dominated by saturated even-numbered chains with smaller amounts (5.4%) of odd numbered normal and branched chains. The main fatty acid of the hump fat is palmitic (34.4%) followed by oleic (28.2%), myristic (10.3%) and stearic (10.0%). PMID- 22059420 TI - Obituary. PMID- 22059421 TI - Unexpected decline in tuberculosis cases coincident with economic recession - United States, 2009. AB - BACKGROUND: Since 1953, through the cooperation of state and local health departments, the U.S. Centers for Disease Control and Prevention (CDC) has collected information on incident cases of tuberculosis (TB) disease in the United States. In 2009, TB case rates declined -11.4%, compared to an average annual -3.8% decline since 2000. The unexpectedly large decline raised concerns that TB cases may have gone unreported. To address the unexpected decline, we examined trends from multiple sources on TB treatment initiation, medication sales, and laboratory and genotyping data on culture-positive TB. METHODS: We analyzed 142,174 incident TB cases reported to the U. S. National Tuberculosis Surveillance System (NTSS) during January 1, 2000-December 31, 2009; TB control program data from 59 public health reporting areas; self-reported data from 50 CDC-funded public health laboratories; monthly electronic prescription claims for new TB therapy prescriptions; and complete genotyping results available for NTSS cases. Accounting for prior trends using regression and time-series analyses, we calculated the deviation between observed and expected TB cases in 2009 according to patient and clinical characteristics, and assessed at what point in time the deviation occurred. RESULTS: The overall deviation in TB cases in 2009 was -7.9%, with -994 fewer cases reported than expected (P < .001). We ruled out evidence of surveillance underreporting since declines were seen in states that used new software for case reporting in 2009 as well as states that did not, and we found no cases unreported to CDC in our examination of over 5400 individual line-listed reports in 11 areas. TB cases decreased substantially among both foreign-born and U.S.-born persons. The unexpected decline began in late 2008 or early 2009, and may have begun to reverse in late 2009. The decline was greater in terms of case counts among foreign-born than U.S.-born persons; among the foreign-born, the declines were greatest in terms of percentage deviation from expected among persons who had been in the United States less than 2 years. Among U.S.-born persons, the declines in percentage deviation from expected were greatest among homeless persons and substance users. Independent information systems (NTSS, TB prescription claims, and public health laboratories) reported similar patterns of declines. Genotyping data did not suggest sudden decreases in recent transmission. CONCLUSIONS: Our assessments show that the decline in reported TB was not an artifact of changes in surveillance methods; rather, similar declines were found through multiple data sources. While the steady decline of TB cases before 2009 suggests ongoing improvement in TB control, we were not able to identify any substantial change in TB control activities or TB transmission that would account for the abrupt decline in 2009. It is possible that other multiple causes coincident with economic recession in the United States, including decreased immigration and delayed access to medical care, could be related to TB declines. Our findings underscore important needs in addressing health disparities as we move towards TB elimination in the United States. PMID- 22059422 TI - Diagnosis of pilonidal sinus on fine needle aspiration cytology. PMID- 22059423 TI - The convergence of type 1 and type 2 diabetes in childhood: the accelerator hypothesis. AB - It seems likely that type 1 and type 2 diabetes lie at different points of the same spectrum, separated by the misunderstanding that one belongs to childhood and the other to adulthood. The spectrum is that of tempo--the rate at which beta cell function is lost over time. A combination of beta cell up-regulation (insulin demand, largely determined by obesity) and the genetically-determined immune response to it ('autoimmunity') determines tempo, ranging from slow to fast with every variant in between. There is good evidence that people who go on to develop type 1 (fast) diabetes are, like those who develop type 2 (slow diabetes), insulin resistant, and overwhelming evidence that body mass plays a key role. The prevention of type 1 diabetes may lie in weight restriction from an early age. PMID- 22059424 TI - Ipsilateral printing in children's mirror-writing: a cause of specific learning disabilities? AB - Previous research has demonstrated that young children produce mirror-image letter-reversals when printing their names in a leftward direction from the midline or right margin of their writing paper. This ability is postulated to be an epiphenomenon of a symmetric, proximal (arm) stage of motor development that ontogenetically precedes lateralization of fine-motor distal (finger) control-a stage in which each arm can be controlled by either side of the brain. From this view, canonical writing in right hemi-space is contralaterally mediated by the left hemisphere and mirror-writing in left hemi-space is ipsilaterally mediated by the right hemisphere. However, evidence of right hemisphere canonical letter processing in dyslexia suggests that this is not always the case. Concordantly, an early study corrected reversals by having children print these errors canonically in left hemi-space and then rightward across the midline into right hemi-space. To further understand this behaviour, the present study investigated mirror-writing in three schools (Public, Montessori, and Waldorf) each differing in how writing is introduced. It was hypothesised that there would be no school differences in mirror-writing if printing had been learned before school-entry and that some children would produce reversals in right hemi-space that were canonically written in left-hemi-space (inverse reversals)-the opposite of the normal pattern. The results showed that 39% of the children demonstrated these inverse reversals. It is discussed how this unexpectedly high incidence may be foundational in the development of the phonologically proficient and deficient subtypes of dyslexia, spelling-dysgraphia, and the left-hand inverted writing posture. PMID- 22059425 TI - gamma-Glutamyl transferase and high-molecular-weight adiponectin levels are synergistically associated with metabolic syndrome and insulin resistance in community-dwelling persons. AB - BACKGROUND: Metabolic syndrome is associated with an increased risk of major cardiovascular events. Decreased high-molecular-weight (HMW) adiponectin levels are associated with metabolic syndrome and its components. Changes in gamma glutamyl transferase (GGT) levels are also associated with metabolic syndrome and could be modulated by HMW adiponectin. METHODS: From a single community, we recruited 822 men (mean age, 61+/-14 years) and 1,097 women (63+/-12 years) during their annual health examination. We investigated whether increased GGT and decreased HMW adiponectin levels are synergistically associated with metabolic syndrome and insulin resistance as evaluated by homeostasis of model assessment of insulin resistance (HOMA-IR). RESULTS: Of these subjects, 141 men (17.2%) and 170 women (15.5%) had metabolic syndrome. In men, the odds ratios (ORs) [(95% confidence interval (CI)] for metabolic syndrome across tertiles of GGT and HMW adiponectin were 1.00, 2.31 (1.25-4.24) and 3.39 (1.75-6.55) and 1.00, 0.51 (0.32 0.82) and 0.30 (0.17-0.54), respectively. In women, the ORs (95% CI) for metabolic syndrome across tertiles of GGT and HMW adiponectin were 1.00, 1.39 (0.81-2.40) and 1.79 (1.06-3.01) and 1.00, 0.35 (0.22-0.55) and 0.27 (0.15-0.46), respectively. The ORs for insulin resistance were increased in relation to GGT only in women, and decreased significantly in relation to HMW adiponectin in both genders. The interaction between increased GGT and decreased HMW adiponectin was a significant and independent determinant for metabolic syndrome and insulin resistance. CONCLUSIONS: These results suggested that higher GGT and lower HMW adiponectin levels are synergistically associated with metabolic syndrome and insulin resistance. PMID- 22059426 TI - Perceiving a calling, living a calling, and job satisfaction: testing a moderated, multiple mediator model. AB - The current study examined the relation between perceiving a calling, living a calling, and job satisfaction among a diverse group of employed adults who completed an online survey (N = 201). Perceiving a calling and living a calling were positively correlated with career commitment, work meaning, and job satisfaction. Living a calling moderated the relations of perceiving a calling with career commitment and work meaning, such that these relations were more robust for those with a stronger sense they were living their calling. Additionally, a moderated, multiple mediator model was run to examine the mediating role of career commitment and work meaning in the relation of perceiving a calling and job satisfaction, while accounting for the moderating role of living a calling. Results indicated that work meaning and career commitment fully mediated the relation between perceiving a calling and job satisfaction. However, the indirect effects of work meaning and career commitment were only significant for individuals with high levels of living a calling, indicating the importance of living a calling in the link between perceiving a calling and job satisfaction. Implications for research and practice are discussed. PMID- 22059427 TI - Perceived racism and mental health among Black American adults: a meta-analytic review. AB - The literature indicates that perceived racism tends to be associated with adverse psychological and physiological outcomes; however, findings in this area are not yet conclusive. In this meta-analysis, we systematically reviewed 66 studies (total sample size of 18,140 across studies), published between January 1996 and April 2011, on the associations between racism and mental health among Black Americans. Using a random-effects model, we found a positive association between perceived racism and psychological distress (r = .20). We found a moderation effect for psychological outcomes, with anxiety, depression, and other psychiatric symptoms having a significantly stronger association than quality of life indicators. We did not detect moderation effects for type of racism scale, measurement precision, sample type, or type of publication. Implications for research and practice are discussed. PMID- 22059428 TI - Therapeutic immediacy across long-term psychodynamic psychotherapy: an evidence based case study. AB - C. E. Hill (2004) recently developed the concept of therapist immediacy to capture discussion by the therapist about the therapeutic relationship that occurs in the here-and-now of a therapy session. This concept has been expanded to include discussion about the therapeutic relationship by both the client and therapist, captured by the term therapeutic immediacy (K. Kuutmann & M. Hilsenroth, 2011). Although prior research has examined the use of therapeutic immediacy across short-term treatment, the present study is the first to examine the use of immediacy across a long-term (4 years) psychotherapy. Also, this is the first study to assess the interrater reliability of therapeutic immediacy, which was found to achieve good to excellent levels across raters. The most frequently used categories of client and therapist immediacy are presented. Finally, the authors provide an in-depth qualitative examination of 5 therapeutic immediacy segments across the treatment judged by the raters to have high levels of depth/intensity (4.5 or higher out of 5) to examine the role of therapeutic immediacy in exploring meaningful treatment issues. Clinical utility, potential limitations, and future research on therapeutic immediacy are discussed. PMID- 22059429 TI - Disentangling the effects of depression symptoms and adult attachment on emotional disclosure. AB - Individuals with high levels of depression symptoms and individuals with insecure attachment orientations have been shown to limit their use of emotional disclosure as a means of emotion regulation. However, little is known about how depression symptoms and insecure attachment orientations might jointly predict whether individuals engage in emotional disclosure. The authors addressed this question using both inter- and intraindividual approaches. College students (N = 121) completed measures of depression symptoms, adult attachment orientation, and generalized disclosure tendencies. To obtain an intraindividual measure of emotional disclosure, participants also completed an online daily diary in which they rated the intensity of the day's most unpleasant event and their disclosure of that event for 7 days. Results indicated that depression symptoms were negatively related to generalized disclosure tendencies and to intraindividual daily intensity-disclosure slopes. Attachment avoidance was negatively related to both generalized disclosure tendencies and to daily disclosure, and attachment anxiety moderated the relation between daily event intensity and disclosure. The authors discuss the implications for theory and counseling psychology practice. PMID- 22059430 TI - A new allocreadiid (Trematoda) species from freshwater fish Heterandria bimaculata (Teleostei: Poeciliidae) in Southeastern Mexico. AB - Paracreptotrema heterandriae n. sp. (Trematoda: Allocreadiidae) is described from the intestine of the freshwater fish Heterandria bimaculata (Teleostei: Poeciliidae) from the upper basin of Rio La Antigua, in Veracruz, Mexico. The new species is distinguished from the 3 others in the Paracreptotrema Choudhury, Perez-Ponce de Leon, Brooks, and Daverdin, 2006 , mainly by having a feeble membranous cirrus sac containing an uncoiled seminal vesicle, instead of a well developed muscular cirrus sac that encloses coiled seminal vesicle, pars prostatica, and ejaculatory duct as in the previously 3 nominal species. Moreover, eggs of the new species are larger than all others ([measurements in micrometers] eggs of P. heterandriae n. sp. 72.5 [70-75] * 40 [35-41]; P. blancoi 55.4 [52.5-62.5] * 38.5 [32.5-42.5]; P. mendezi 46 * 37; P. profundulusi 57 [52 60] * 27.8 [25-30]). PMID- 22059431 TI - Java-based diabetes type 2 prediction tool for better diagnosis. AB - BACKGROUND: The concept of classification of clinical data can be utilized in the development of an effective diagnosis system by taking the advantage of computational intelligence. Diabetes disease diagnosis via proper interpretation of the diabetes data is an important problem in neural networks. Unfortunately, although several classification studies have been carried out with significant performance, many of the current methods often fail to reach out to patients. Graphical user interface-enabled tools need to be developed through which medical practitioners can simply enter the health profiles of their patients and receive an instant diabetes prediction with an acceptable degree of confidence. METHODS: In this study, the neural network approach was used for a dataset of 768 persons from a Pima Indian population living near Phoenix, AZ. A neural network mixture of experts model was trained with these data using the expectation-minimization algorithm. RESULTS: The mixture of experts method was used to train the algorithm with 97% accuracy. A graphical user interface was developed that would work in conjunction with the trained network to provide the output in a presentable format. CONCLUSIONS: This study provides a machine-implementable approach that can be used by physicians and patients to minimize the extent of error in diagnosis. The authors are hopeful that replication of results of this study in other populations may lead to improved diagnosis. Physicians can simply enter the health profile of patients and get the diagnosis for diabetes type 2. PMID- 22059432 TI - Food choice: beyond the chemical content. AB - How are food choices formulated? Which are the factors that mostly affect food choice? These questions are crucially important both for efforts in food innovation and for institutions that face consequences and costs of diets that are harmful to human health and to the environment. On these matters, several reports have been developed following the angel of various disciplines, focusing on the analysis of the factors affecting food choices. Large-scale research on consumption behaviours has neither stopped the growing number of unsuccessful products entering the market, nor provided adequate support for institutions that are taking elaborate actions towards promoting health-orientated behaviours. These preliminary remarks highlight the need to think about the approaches and categories with which research programmes on food choices should be updated. This article discusses the reasons why food choices are determined by beliefs and identity, are conditioned by social images that influence preferences by indicating to individuals what foods are 'good' and 'right'; belong to the field of individual choice, and therefore, cannot be assimilated into medical prescriptions or merely reduced to a question of rules. Taste involves beliefs and identity as well as perceptions. This is why it has to be analyzed as a cultural and relational object. This paper aims to explore the complex mix of influences on food choice stressing that food choice is a matter of identity. PMID- 22059433 TI - HIV type 1 genetic diversity in newly diagnosed Cuban patients. AB - Knowledge of the genetic diversity of HIV-1 constitutes a fundamental premise in the epidemiological surveillance. In the present study, the HIV-1 genetic variability from 142 Cuban patients who were diagnosed with HIV-1 infection during 2009 and 2010 was determined. HIV-1 subtypes were determined by partial RT PCR and sequencing of the HIV-1 pol gene. The phylogenetic analysis showed that 47 (33.1 %) samples were subtypes B and 95 (66.9 %) were non-B subtypes, where G, H, and C subtypes, as well as the recombinant forms CRF19_cpx, CRF18_cpx, and CRFs BG, were included. The circulation of CRF05_DF was detected for the first time in Cuba. The analyses of recombinants showed the presence of recombinant CRF18_cpx/CRF19_cpx. The study confirms the high genetic diversity of HIV-1 and the circulation of new genetic variants in the studied population, which indicates the importance of maintaining constant epidemiological surveillance in Cuba. PMID- 22059434 TI - Multimerization and aggregation of native-state insulin: effect of zinc. AB - The aggregation of insulin is complicated by the coexistence of various multimers, especially in the presence of Zn(2+). Most investigations of insulin multimerization tend to overlook aggregation kinetics, while studies of insulin aggregation generally pay little attention to multimerization. A clear understanding of the starting multimer state of insulin is necessary for the elucidation of its aggregation mechanism. In this work, the native-state aggregation of insulin as either the Zn-insulin hexamer or the Zn-free dimer was studied by turbidimetry and dynamic light scattering, at low ionic strength and pH near pI. The two states were achieved by varying the Zn(2+) content of insulin at low concentrations, in accordance with size-exclusion chromatography results and literature findings (Tantipolphan, R.; Romeijn, S.; Engelsman, J. d.; Torosantucci, R.; Rasmussen, T.; Jiskoot, W. J. Pharm. Biomed. 2010, 52, 195). The much greater aggregation rate and limiting turbidity (tau(infinity)) for the Zn-insulin hexamer relative to the Zn-free dimer was explained by their different aggregation mechanisms. Sequential first-order kinetic regimes and the concentration dependence of tau(infinity) for the Zn-insulin hexamer indicate a nucleation and growth mechanism, as proposed by Wang and Kurganov (Wang, K.; Kurganov, B. I. Biophys. Chem. 2003, 106, 97). The pure second-order process for the Zn-free dimer suggests isodesmic aggregation, consistent with the literature. The aggregation behavior at an intermediate Zn(2+) concentration appears to be the sum of the two processes. PMID- 22059435 TI - Gyroidal metal-organic frameworks. AB - The gyroid is ubiquitous for underlying the construction of natural substance and artificial zeolites, but it has been, surprisingly, overlooked by chemists who work in the field of metal-organic frameworks (MOFs). In this work, a series of gyroidal MOFs with gie topology, constructed from 1,2-bis((5H-imidazol-4 yl)methylene)hydrazine and octahedral metal ions, such as Zn(II), Mn(II), Cu(II), and Ni(II), have been synthesized. The Zn(II) analogue, named as STU-1, shows exceptional thermal and chemical stabilities, and exhibits permanent porosity and CO(2) capture ability. PMID- 22059436 TI - Carbon dioxide coordination and activation by niobium oxide molecules. AB - Carbon dioxide coordination and activation by niobium oxide molecules were studied by matrix isolation infrared spectroscopy. It was found that the niobium monoxide molecule reacted with carbon dioxide to form the niobium dioxide carbonyl complex NbO(2)(eta(1)-CO) spontaneously on annealing in solid neon. The observation of the spontaneous reaction is consistent with theoretical predictions that this carbon dioxide activation process is both thermodynamically exothermic and kinetically facile. In contrast, four niobium dioxide-carbon dioxide complexes exhibiting three different coordination modes of CO(2) were formed from the reactions between niobium dioxide and carbon dioxide, which proceeded with the initial formation of the eta(1)-O bound NbO(2)(eta(1)-OCO) and NbO(2)(eta(1)-OCO)(2) complexes on annealing. The NbO(2)(eta(1)-OCO) complex rearranged to the eta(2)-O,O bound NbO(2)(eta(2)-O(2)C) isomer under visible light irradiation, while the NbO(2)(eta(1)-OCO)(2) complex isomerized to the NbO(2)(eta(1)-OCO)(eta(2)-OC)O structure involving an eta(2)-C,O ligand under IR excitation. In these niobium dioxide carbon dioxide complexes, the eta(1)-O coordinated CO(2) ligand serves as an electron donor, whereas both the eta(2)-C,O and eta(2)-O,O coordinated CO(2) ligands act as electron acceptors. PMID- 22059437 TI - Comprehensive comparison of iTRAQ and label-free LC-based quantitative proteomics approaches using two Chlamydomonas reinhardtii strains of interest for biofuels engineering. AB - Comprehensive comparisons of quantitative proteomics techniques are rare in the literature, yet they are crucially important for optimal selection of approaches and methodologies that are ideal for a given proteomics initiative. In this study, two LC-based quantitative proteomics approaches--iTRAQ and label-free- were implemented using the LTQ-Orbitrap Velos platform. For this comparison, the model used was the total protein content from two Chlamydomonas reinhardtii strains in the context of alternative biofuels production. The strain comparison includes sta6 (a starch-less mutant of cw15) that produces twice as many lipid bodies (LB) containing triacylglycerols (TAGs) as its parental strain cw15 (a cell wall-deficient C. reinhardtii strain) under nitrogen starvation. Internal standard addition was used to rigorously assess the quantitation accuracy and precision of each method. Results from iTRAQ-4plex labeling using HCD (higher energy collision-induced dissociation) fragmentation were compared to those obtained using a label-free approach based on the peak area of intact peptides and collision-induced dissociation. The accuracy and precision, number of identified/quantified proteins and statistically significant protein differences detected, as well as efficiency of these two quantitative proteomics methods were evaluated and compared. Four technical and three biological replicates of each strain were performed to assess both the technical and biological variation of both approaches. A total of 896 and 639 proteins were identified with high confidence, and 329 and 124 proteins were quantified significantly with label free and iTRAQ, respectively, using biological replicates. The results showed that both iTRAQ labeling and label-free methods provide high quality quantitative and qualitative data using nano-LC coupled with the LTQ-Orbitrap Velos mass spectrometer, but the selection of the optimal approach is dependent on experimental design and the biological question to be addressed. The functional categorization of the differential proteins between cw15 and sta6 reveals already known but also new mechanisms likely responsible for the production of lipids in sta6 and sets the baseline for future studies aimed at engineering these strains for high oil production. PMID- 22059438 TI - Catalytic, enantioselective intramolecular hydroamination of primary amines tethered to di- and trisubstituted alkenes. AB - The in situ preparation of chiral amido alkyl ate yttrium complexes from an array of chiral N-benzyl-like-substituted binaphthyldiamines is reported. These chiral heteroleptic complexes are shown to be efficient catalysts for the enantioselective intramolecular hydroamination of primary amines tethered to sterically demanding alkenes at high reaction temperatures. Fine tuning of their chiral environment allowed up to 77% ee to be reached for the cyclization of aminoalkenes bearing 1,2-dialkyl-substituted carbon-carbon double bonds. These chiral complexes also demonstrate the ability to promote the cyclization of amine tethered trisubstituted alkenes in up to 55% ee, as the first report of the formation of enantioenriched quaternary centers by an hydroamination reaction. PMID- 22059439 TI - Cross-linked perylene diimide-based n-type interfacial layer for inverted organic photovoltaic devices. AB - This contribution describes the synthesis and characterization of a perylene diimide (PDI)-based n-type semiconductor and its application to organic photovoltaic (OPV) devices having inverted architecture. Films of N,N'-bis(3 trimethoxysilylpropyl)-1,6,7,12-tetrachloroperylene-3,4,9,10-tetracarboxyldiimide (Cl(4)PSi(2)) and blends of this material with various polymers are solution deposited on tin-doped indium oxide (ITO) substrates as interfacial layers (IFLs). The organic IFL described in this work is based on the air- and light stable PDI core, annealed at low temperatures compatible with flexible substrates, and crosslinks in air for compatibility with device fabrication. Morphological, optical, and electrochemical analysis of these IFL films demonstrate predominantly smooth surfaces and HOMO and LUMO energies of ~4.5 and 7.0 eV, respectively, which are ideal for accepting electrons and blocking holes in inverted devices. A cationic silane species is added to the Cl(4)PSi(2) at an optimum ~2-5 wt % to reduce IFL series resistance and enhance device performance. Also, a short light soaking procedure is necessary for completed devices to achieve high fill factors in current density-voltage analysis, a phenomenon previously only observed for inverted devices having an n-type inorganic IFL. PMID- 22059440 TI - The influence of clinical risk factors on pre-operative B-type natriuretic peptide risk stratification of vascular surgical patients. AB - The role of the revised cardiac risk index in risk stratification has recently been challenged by studies reporting on the superior predictive ability of pre operative B-type natriuretic peptides. We found that in 850 vascular surgical patients initially risk stratified using B-type natriuretic peptides, reclassification with the number of revised cardiac risk index risk factors worsened risk stratification (p < 0.05 for > 0, > 2, > 3 and > 4 risk factors, and p = 0.23 for > 1 risk factor). When evaluated with pre-operative B-type natriuretic peptides, none of the revised cardiac risk index risk factors were independent predictors of major adverse cardiac events in vascular patients. The only independent predictor was B-type natriuretic peptide stratification (OR 5.1, 95% CI 1.8-15 for the intermediate class, and OR 25, 95% CI 8.7-70 for the high risk class). The clinical risk factors in the revised cardiac risk index cannot improve a risk stratification model based on B-type natriuretic peptides. PMID- 22059441 TI - Mood, motivation, and misinformation: aging and affective state influences on memory. AB - Normative age differences in memory have typically been attributed to declines in basic cognitive and cortical mechanisms. The present study examined the degree to which dominant everyday affect might also be associated with age-related memory errors using the misinformation paradigm. Younger and older adults viewed a positive and a negative event, and then were exposed to misinformation about each event. Older adults exhibited a higher likelihood than young adults of falsely identifying misinformation as having occurred in the events. Consistent with expectations, strength of the misinformation effect was positively associated with dominant mood, and controlling for mood eliminated any age effects. Also, motivation to engage in complex cognitive activity was negatively associated with susceptibility to misinformation, and susceptibility was stronger for negative than for positive events. We argue that motivational processes underlie all of the observed effects, and that such processes are useful in understanding age differences in memory performance. PMID- 22059442 TI - Structural properties of hydrolyzed high-amylose rice starch by alpha-amylase from Bacillus licheniformis. AB - High-amylose cereal starch has a great benefit on human health through its resistant starch (RS) content. Enzyme hydrolysis of native starch is very helpful in understanding the structure of starch granules and utilizing them. In this paper, native starch granules were isolated from a transgenic rice line (TRS) enriched with amylose and RS and hydrolyzed by alpha-amylase. Structural properties of hydrolyzed TRS starches were studied by X-ray powder diffraction, Fourier transform infrared, and differential scanning calorimetry. The A-type polymorph of TRS C-type starch was hydrolyzed faster than the B-type polymorph, but the crystallinity did not significantly change during enzyme hydrolysis. The degree of order in the external region of starch granule increased with increasing enzyme hydrolysis time. The amylose content decreased at first and then went back up during enzyme hydrolysis. The hydrolyzed starches exhibited increased onset and peak gelatinization temperatures and decreased gelatinization enthalpy on hydrolysis. These results suggested that the B-type polymorph and high amylose that formed the double helices and amylose-lipid complex increased the resistance to BAA hydrolysis. Furthermore, the spectrum results of RS from TRS native starch digested by pancreatic alpha-amylase and amyloglucosidase also supported the above conclusion. PMID- 22059443 TI - Management of acute coronary syndromes at hospital discharge: do targeted educational interventions improve practice quality? AB - Evidence-based guidelines exist for the management of patients with acute coronary syndromes (ACS), yet adherence is suboptimal. The Discharge Management of Acute Coronary Syndrome project used a quality improvement approach, with targeted intervention strategies to optimize: prescription of guideline recommended medications; education regarding lifestyle modifications, including cardiac rehabilitation (CR); and communication between hospital staff, patients, and general practitioners. Hospitals across Australia participated in a quality improvement cycle of audit, feedback, intervention, and reaudit. Interventions involved educational meetings, academic detailing and point-of-care reminders, and feedback of baseline audit results. Outcome measures included prescription of guideline-recommended medications, referral to CR, and documentation and communication of management plan. At baseline, 49 hospitals recruited 1,545 patients, and postintervention, 45 hospitals remained active in the project and recruited 1,589 patients. Three thousand and thirty-four hospital staff attended group education or academic detailing sessions. Postintervention, there was a significant increase in the prescription of all four guideline-recommended medications (69% vs. 57%; p<.0001); short-acting nitrates (68% vs. 56%; p<.0001); and documented referral to CR (68% vs. 57%; p<.0001). There were significant increases in documented discharge medication counselling, smoking cessation counselling, and communication of management plans. Targeted educational interventions used as part of a quality improvement cycle can enhance adherence to evidence-based guidelines for the management of patients with ACS. PMID- 22059444 TI - History and structures of telecommunication in pathology, focusing on open access platforms. AB - BACKGROUND: Telecommunication has matured to a broadly applied tool in diagnostic pathology. TECHNOLOGY AND SYSTEMS: Contemporary with the development of fast electronic communication lines (Integrated digital network services (ISDN), broad band connections, and fibre optics, as well as the digital imaging technology (digital camera), telecommunication in tissue--based diagnosis (telepathology) has matured. Open access (internet) and server--based communication have induced the development of specific medical information platforms, such as iPATH, UICC TPCC (telepathology consultation centre of the Union International against Cancer), or the Armed Forces Institute of Pathology (AFIP) teleconsultation system. They have been closed, and are subject to be replaced by specific open access forums (Medical Electronic Expert Communication System (MECES) with embedded virtual slide (VS) technology). MECES uses php language, data base driven mySqL architecture, X/L-AMPP infrastructure, and browser friendly W3C conform standards. EXPERIENCES: The server--based medical communication systems (AFIP, iPATH, UICC-TPCC) have been reported to be a useful and easy to handle tool for expert consultation. Correct sampling and evaluation of transmitted still images by experts reported revealed no or only minor differences to the original images and good practice of the involved experts. beta tests with the new generation medical expert consultation systems (MECES) revealed superior results in terms of performance, still image viewing, and system handling, especially as this is closely related to the use of so--called social forums (facebook, youtube, etc.). BENEFITS AND EXPECTATIONS: In addition to the acknowledged advantages of the former established systems (assistance of pathologists working in developing countries, diagnosis confirmation, international information exchange, etc.), the new generation offers additional benefits such as acoustic information transfer, assistance in image screening, VS technology, and teaching in diagnostic sampling, judgement, and verification. PMID- 22059445 TI - The guanine cap of human guanylate-binding protein 1 is responsible for dimerization and self-activation of GTP hydrolysis. AB - Human guanylate-binding protein 1 (hGBP1) belongs to the superfamily of large, dynamin-related GTPases. The expression of hGBP1 is induced by stimulation with interferons (mainly interferon-gamma), and it plays a role in different cellular responses to inflammatory cytokines, e.g. pathogen defence, control of proliferation, and angiogenesis. Although other members of the dynamin superfamily show a diversity of cellular functions, they share a common GTPase mechanism that relies on nucleotide-controlled oligomerization and self activation of the GTPase. Previous structural studies on hGBP1 have suggested a mechanism of GTPase and GDPase activity that, as a critical step, involves dimerization of the large GTP-binding domains. In this study, we show that the guanine cap of hGBP1 is the key structural element responsible for dimerization, and is thereby essential for self-activation of the GTPase activity. Studies of concentration-dependent GTP hydrolysis showed that mutations of residues in the guanine cap, in particular Arg240 and Arg244, resulted in higher dissociation constants of the dimer, whereas the maximum hydrolytic activity was largely unaffected. Additionally, we identified an intramolecular polar contact (Lys62 Asp255) whose mutation leads to a loss of self-activation capability and controlled oligomer formation. We suggest that this contact structurally couples the guanine cap to the switch regions of the GTPase, translating the structural changes that occur upon nucleotide binding to a change in oligomerization and self-activation. PMID- 22059446 TI - Study protocol of a Dutch smoking cessation e-health program. AB - BACKGROUND: The study aims to test the differential effects of a web-based text and a web-based video-driven computer-tailored approach for lower socio-economic status (LSES) and higher socio-economic status (HSES) smokers which incorporate multiple computer-tailored feedback moments. The two programs differ only in the mode of delivery (video- versus text-based messages). The paper aims to describe the development and design of the two computer-tailored programs. METHODS/DESIGN: Respondents who smoked at the time of the study inclusion, who were motivated to quit within the following six months and who were aged 18 or older were included in the program. The study is a randomized control trial with a 2 (video/text) * 2(LSES/HSES) design. Respondents were assigned either to one of the intervention groups (text versus video tailored feedback) or to the control group (non tailored generic advice). In all three conditions participants were asked to fill in the baseline questionnaire based on the I-Change model. The questionnaire assessed socio-demographics, attitude towards smoking, knowledge, self-efficacy, social influence, depression, level of addiction, action planning, goal actions, intention to quit smoking, seven-day point prevalence and continued abstinence. Follow-up measurements were conducted at six and twelve months after baseline. DISCUSSION: The present paper describes the development of the two computer tailored smoking cessation programs, their components and the design of the study. The study results reveal different working mechanisms of multiple tailored smoking cessation interventions and will help us to gain more insight into effective strategies to target different subgroups, especially smokers with a lower socio-economic status. TRIAL REGISTRATION: Dutch Trial Register NTR3102. PMID- 22059447 TI - Effects of categorical labels on similarity judgments: a critical analysis of similarity-based approaches. AB - Our goal in the present study was to evaluate the claim that category labels affect children's judgments of visual similarity. We presented preschool children with discriminable and identical sets of animal pictures and asked them to make perceptual judgments in the presence or absence of labels. Our findings indicate that children who are asked to make perceptual judgments about identical items judge discriminable items less accurately when making subsequent similarity judgments. Thus, labels do not generally affect children's perceptual similarity judgments; rather, children's reliance on labels to make similarity judgments appears to be attributable to flaws in the methodological approaches used in prior studies. These results have implications for the role of perceptual and conceptual information in children's categorization and induction. PMID- 22059448 TI - Socialization in context: exploring longitudinal correlates of mothers' value messages of compassion and caution. AB - This study examined correlates of mothers' value messages using mother and adolescent reports across 3 years (N =1,638 dyads). Two fundamental socialization dimensions were assessed: compassion messages (e.g., caring for others) and caution messages (e.g., being wary of others). Multilevel models revealed distinct between-person and within-person correlates for mothers' compassion and caution messages. Individual differences in compassion messages were predicted by family context (e.g., mothers' knowledge of friends and concerns for their child's future) and neighborhood cohesion. Within-person effects demonstrated that compassion declined in concert with adolescents' experiences of being bullied. Caution messages were predicted by mothers' education levels, race/ethnicity, and marital status, and increased in relation to mothers' concerns and perceptions that illegal substances were easily attainable in the community. Tests of age, period, and cohort effects unexpectedly revealed that longitudinal changes in compassion and caution were best explained by period effects. Consistent with new developments in value socialization theory, results suggest that mothers place emphasis on certain values on the basis of their backgrounds, their children's characteristics, and the broader social context. PMID- 22059449 TI - Weathering the great recession: psychological and behavioral trajectories in the transition from school to work. AB - Studies of career development highlight the importance of finding a good "fit" between individual values, needs, and abilities and the experiences and rewards to be found in particular occupations. Rapid economic change and labor market turbulence make career choice and development life-long processes. Still, early careers are particularly unstable, as young workers move from "survival jobs" to "career jobs" in their quest for a good person-job fit. Little is known, however, about the psychological orientations and behaviors in the postadolescent period that foster longer term success in the world of work. The maintenance of high aspirations, crystallization of career goals, and intensive job search may be particularly important. Using multilevel latent class analysis applied to longitudinal data obtained from 1,010 youth surveyed by the ongoing Youth Development Study (YDS), we examine the interrelations of psychological orientations and behaviors indicative of agentic striving from age 18 to 31 years. In addition, we assess how these trajectories influence adaptation to declining labor market conditions during the severe economic recession that began in 2007. We find that those who maintain high aspiration and certainty over career goals were better insulated against unemployment between 2007 and 2009 (ages 33-35), even when educational and self-identified career attainments, adolescent achievement orientations, and social background variables indicative of advantage are controlled. They also had higher hourly wages in 2009. PMID- 22059450 TI - Adult age differences in categorization and multiple-cue judgment. AB - We often need to infer unknown properties of objects from observable ones, just like detectives must infer guilt from observable clues and behavior. But how do inferential processes change with age? We examined young and older adults' reliance on rule-based and similarity-based processes in an inference task that can be considered either a categorization or a multiple-cue judgment task, depending on the nature of the criterion (binary vs. continuous). Both older and young adults relied on rule-based processes in the multiple-cue judgment task. In the categorization task, however, the majority of older adults relied on rule based processes while young adults preferred similarity-based processes. Moreover, older adults who relied on rule-based processes performed poorly compared with young adults who relied on the same process, suggesting that aging is associated with deficits in applying rule-based processes. PMID- 22059451 TI - Interactions between serotonin transporter gene haplotypes and quality of mothers' parenting predict the development of children's noncompliance. AB - The LPR and STin2 polymorphisms of the serotonin transporter gene (SLC6A4) were combined into haplotypes that, together with quality of maternal parenting, were used to predict initial levels and linear change in children's (N = 138) noncompliance and aggression from age 18-54 months. Quality of mothers' parenting behavior was observed when children were 18 months old, and nonparental caregivers' reports of noncompliance and aggression were collected annually from 18 to 54 months of age. Quality of early parenting was negatively related to the slope of noncompliance only for children with the LPR-S/STin2-10 haplotype and to 18-month noncompliance only for children with haplotypes that did not include LPR S. The findings support the notion that SLC6A4 haplotypes index differential susceptibility to variability in parenting quality, with certain haplotypes showing greater reactivity to both supportive and unsupportive environments. These different genetic backgrounds likely reflect an evolutionary response to variation in the parenting environment. PMID- 22059452 TI - Boechera, a model system for ecological genomics. AB - The selection and development of a study system for evolutionary and ecological functional genomics (EEFG) depend on a variety of factors. Here, we present the genus Boechera as an exemplary system with which to address ecological and evolutionary questions. Our focus on Boechera is based on several characteristics as follows: (i) native populations in undisturbed habitats where current environments reflect historical conditions over several thousand years; (ii) functional genomics benefitting from its close relationship to Arabidopsis thaliana; (iii) inbreeding tolerance enabling development of recombinant inbred lines, near-isogenic lines and positional cloning; (iv) interspecific crosses permitting mapping for genetic analysis of speciation; (v) apomixis (asexual reproduction by seeds) in a genetically tractable diploid; and (vi) broad geographic distribution in North America, permitting ecological genetics for a large research community. These characteristics, along with the current sequencing of three Boechera species by the Joint Genome Institute, position Boechera as a rapidly advancing system for EEFG studies. PMID- 22059453 TI - Caffeine is protective in patients with non-alcoholic fatty liver disease. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is the most common cause of primary liver disease. Although recent studies have found that coffee drinking is protective against end stage chronic liver disease, there are scarce caffeine intake data in NAFLD specifically. AIM: To investigate the effects of dietary behaviour in NAFLD patients, using four continuous cycles of the National Health and Nutrition Examination Surveys (NHANES 2001-2008). METHODS: Using data from four continuous cycles of NHANES, dietary intake questionnaires that list 62 nutrition components. Logistic regression was used to identify independent predictors of NAFLD among nutrition components after adjustment for potential clinical confounders. All analyses were run using sas 9.1 and SUDAAN 10.0 (SAS Institute Inc., Cary, NC, USA). RESULTS: Of the 62 nutrient components used for the univariate analysis, 38% were significant (P-value <0.05) in NAFLD with caffeine consumption being higher in the control group (P-value <0.001). The multivariate analysis using demographics, clinical parameters and nutritional components found five factors independently associated with NAFLD [African American Race P-value <0.001); Male gender P-value <0.001); Obesity (BMI >= 30) P-value <0.001); Caffeine intake (mg) P-value <0.001) and total plain water consumption (g) P value <= 0.02)]. CONCLUSIONS: Our analysis shows that caffeine intake is independently associated with a lower risk for NAFLD suggesting a potential protective effect. These data necessitate further research to elucidate the mechanism by which caffeine can protect against NAFLD. PMID- 22059454 TI - A multi-residue method for the determination of 90 pesticides in matrices with a high water content by LC-MS/MS without clean-up. AB - A method using QuEChERS extraction and LC-MS/MS in electrospray positive ionisation mode was developed and validated for the analysis of 90 pesticides in a high water content matrix (tomato) in a single chromatographic run. To assess the intra-laboratory reproducibility of the method, validation was conducted on four different days by two different analysts. The validation data was treated using a spreadsheet developed in-house, which sets the most appropriate model for linear fit by determining whether the residuals of the calibration curves are homocedastic or heterocedastic. A statistical test for the significance of regression was also carried out. Calibration was always matrix-matched and the curves were obtained over the range 0.0075-0.10 or 0.020-0.125 mg kg(-1). Identification of analytes was based on retention times and MRM ratios. Recoveries were assessed at four different levels for each analyte and were between 73 and 106%, with relative standard deviations under reproducibility conditions of <20%. The measurement uncertainties of the method for each pesticide analysed were below 50%. Previous validation of the same method, applied to papaya samples and satisfactory results obtained in various proficiency tests with different high water content matrices, demonstrated the applicability of the method to these classes of commodities, without clean-up. The validated method will be applied routinely in the pesticide residues monitoring programme that constitutes the National Residue and Contaminant Control Plan of Brazil. PMID- 22059456 TI - Support of the failing left ventricle: extracorporeal life support plus blade and balloon atrioseptostomy as an alternative option. PMID- 22059457 TI - Lidocaine toxicity secondary to local anesthesia administered in the community for elective circumcision. AB - We report three previously healthy infants aged, respectively, 23 days, 6 weeks, and 3 months with systemic lidocaine toxicity following administration of subcutaneous lidocaine for regional anesthesia during an elective circumcision. The patients developed a generalized seizure requiring endotracheal intubation but recovered fully with supportive care. We report the clinical details of these cases as well as a review of lidocaine toxicity. PMID- 22059458 TI - The role of asymmetric dimethyl arginine and oxidant/antioxidant system in preeclampsia. AB - Preeclampsia is a syndrome characterized by hypertension and proteinuria. The aim of this study is to find the relationship between preeclampsia, asymmetric dimethyl arginine (ADMA), and the oxidant/antioxidant system. Twenty-one preeclamptic and 28 normal pregnant women were included in this study. In cord bloods, ADMA and oxidant/antioxidant parameters were measured. Asymmetric dimethyl arginine levels were significantly increased in preeclamptic pregnancies compared to the control group (p = 0.006). The activities of antioxidant enzymes and malondialdehyde levels were increased in the preeclamptic group compared to the control group (p < 0.001, p = 0.022, p < 0.001, p < 0.001, respectively). Development of endothelial dysfunction and oxidative stress may play a role in developing preeclampsia. PMID- 22059459 TI - Evaluation of fetal lungs and stomach in the determination of amniotic sac infection. AB - This study evaluated neutrophils in fetal lung/stomach, in association with chorioamnionitis. Reports/slides from fetuses 13-24 weeks with a confirmed histologic diagnosis of placental chorioamnionitis were reviewed. There were 94 cases with no neutrophils in the lungs or stomach, and 106 with neutrophils in lungs, stomach, or both (53%). Thirteen percent showed neutrophils in the lungs only. Fetuses with no neutrophils were older than those with neutrophils in the stomach only (p = 0.008). Neutrophils in fetal lungs/stomach are common, and may confirm chorioamnionitis when the placenta is not available. Submission of gastric sections increases identification of chorioamnionitis. PMID- 22059460 TI - Unilateral sclerocornea and tracheal stenosis: unusual findings in a patient with Goldenhar anomaly. AB - The Goldenhar anomaly (GA) is a heterogeneous field defect of uncertain cause and wide variability of expression, characterized by facial phenotypes, usually asymmetric and unilateral, accompanied by various combinations and gradations of cardiac, skeletal, renal, and central nervous system defects. We report the pathologic findings in a 5-month-old boy with GA, tracheal stenosis, and left unilateral sclerocornea. To the best of our knowledge this is the first description of sclerocornea in a patient with GA. PMID- 22059461 TI - Ganglia/nerve fibers ratio correlates with the need for surgery in patients diagnosed with Hirschsprung's disease allied disorder (HAD). AB - Treatment in Hirschsprung's disease allied disorder (HAD) is surgical. In HAD, surgery is always a question. We investigated the value of ganglia/nerve fibers ratio in prediction of the need for invasive procedures in HAD. Sections of full thickness bowel specimens of 14 patients were stained with antibodies marking ganglia (Anti-Neuron-Specific Enolase, Anti-NSE) and marking nerve fibers (S 100). Six out of seven patients indicated for surgery had low ganglia/nerve fibers ratio. Five out of seven patients, not showing the need for surgery, had high ganglia/nerve fibers ratio. We propose that a lower ganglia/nerve fiber ratio can be used as a predictor of increased need for surgery in HAD. PMID- 22059462 TI - Funisitis and chorionic vasculitis: relation to chorioamnionitis, timing and scoring. AB - Five hundred consecutive cases with histologic chorioamnionitis and umbilical cord inflammation were analyzed to develop a staging system for funisitis and to correlate stage of funisitis with stage of chorioamnionitis in order to estimate the timing of various stages of funisitis. Funisitis progresses through venous involvement (with or without Wharton's jelly inflammation) to arterial involvement without Wharton's jelly and then full involvement of all three vessels and surrounding Wharton's jelly. Arterial involvement and full funisitis are strongly associated with stage III/IV chorioamnionitis, and imply a significant time interval following the onset of amniotic cavity inflammation. PMID- 22059463 TI - The fallacy of reduction. AB - The "accelerator hypothesis" has made a significant impact on research into the etiology of type 1 diabetes. Some, but not all prospective studies have confirmed a weak association between insulin resistance and faster progression to diabetes among persons with advanced islet autoimmunity. However, there is hardly any evidence that insulin resistance can cause development of islet autoimmunity, thus be responsible for the ongoing pandemic of type 1 diabetes in children. PMID- 22059464 TI - Survey: immune function and immunotoxicity assessment in dogs. AB - While immunotoxicology evaluations are often conducted in either rodents or non human primates, findings in standard toxicology studies may trigger additional investigations in dogs. A survey sponsored by the HESI Immunotoxicology Technical Committee, and described herein, was conducted to gather information regarding the extent and nature of immunology and immunotoxicity assessments available in the dog, and the need thereof. The survey was issued via e-mail to scientists affiliated with 39 organizations in industry and academia, including contract research organizations, academic research organizations, pharmaceutical companies, and veterinary practices. Fifteen institutions responded, including 10 biotechnology or pharmaceutical industry organizations, 4 contract research organizations, and 1 academic institution. Responses indicated that indeed, immunological assessments in dogs are necessary for research and/or toxicology purposes. The survey demonstrated that multiple types of assays are used in the dog model, including assessment of T-cell-dependent antibody responses, immunoglobulins, complement CH(50), cytokines and cytokine mRNAs, lymphocyte proliferation in response to T-cell mitogens, neutrophil activation, phagocytosis, and immunophenotyping of several cell types. The survey also revealed that certain assays/endpoints are not available in the dog (complement components, NK immunophenotyping, T-cell activation and memory immunophenotyping) or require further optimization (ex vivo cytolysis assays such as CTL and NK function, B-cell proliferation in response to LPS). In addition, the survey indicated that a greater understanding of the specificity of the available immunophenotyping reagents is needed. PMID- 22059465 TI - Resistance, mobilization and militancy: nurses on strike. AB - Drawing on nurses' strikes in many countries, this paper explores nurse militancy with reference to professionalism and the commitment to service; patriarchal practices and gendered subordination; and proletarianization and the confrontation with healthcare restructuring. These deeply entangled trajectories have had a significant impact on the work, consciousness and militancy of nurses and have shaped occupation-specific forms of resistance. They have produced a pattern of overlapping solidarities--occupational solidarity, gendered alliances and coalitions around healthcare restructuring--which have supported, indeed promoted, militancy among nurses, despite the multiple forces arrayed against them. The professional commitments of nurses to the provision of care have confronted healthcare restructuring, nursing shortages, intensification of work, precarious employment and gendered hierarchies with a militant discourse around the public interest, and a reconstitution and reclamation of 'caring', what I call the politicisation of caring. In fact, nurses' dedication to caring work in the late twentieth and early twenty-first centuries may encourage rather than dissuade them from going on strike. This paper uses a trans-disciplinary methodology, qualitative material in the form of strike narratives constructed from newspaper archives, and references to the popular and scholarly literature on nursing militancy. PMID- 22059466 TI - A genetic variant in the promoter region of Toll-like receptor 9 and cervical cancer susceptibility. AB - The Toll-like receptors (TLRs) are important for the innate immune system by recognizing pathogen-associated molecular patterns expressed in infectious agents. E6 and E7 protein from HPV16 suppress the host immune response by regulating the TLR9 transcript. Therefore, we hypothesized that a single nucleotide polymorphism in TLR9 may contribute to cervical cancer. We genotyped TLR9 -1486T/C (rs187084) in a case-control study of 712 cervical cancer cases and 717 cancer-free controls in Chinese women. Logistic regression analyses showed that the rs187084 heterozygote TC was associated with a significantly increased risk of cervical cancer (adjusted OR=1.28, 95% CI=1.01-1.62), compared with the TT genotype. Although the variant homozygote was associated with a nonsignificantly increased cervical cancer risk, the TC/CC genotypes contributed to the risk of cervical cancer in the dominant genetic model (adjusted OR=1.24, 95% CI=1.01-1.53). The findings indicate that TLR9 -1486T/C (rs187084) may contribute to cervical cancer carcinogenesis. PMID- 22059467 TI - A semi-automated method for bone age assessment using cervical vertebral maturation. AB - OBJECTIVE: To propose a semi-automated method for pattern classification to predict individuals' stage of growth based on morphologic characteristics that are described in the modified cervical vertebral maturation (CVM) method of Baccetti et al. MATERIALS AND METHODS: A total of 188 lateral cephalograms were collected, digitized, evaluated manually, and grouped into cervical stages by two expert examiners. Landmarks were located on each image and measured. Three pattern classifiers based on the Naive Bayes algorithm were built and assessed using a software program. The classifier with the greatest accuracy according to the weighted kappa test was considered best. RESULTS: The classifier showed a weighted kappa coefficient of 0.861 +/- 0.020. If an adjacent estimated pre-stage or poststage value was taken to be acceptable, the classifier would show a weighted kappa coefficient of 0.992 +/- 0.019. CONCLUSION: Results from this study show that the proposed semi-automated pattern classification method can help orthodontists identify the stage of CVM. However, additional studies are needed before this semi-automated classification method for CVM assessment can be implemented in clinical practice. PMID- 22059468 TI - Active and passive self-ligation: a myth? Part 1: torque control. AB - OBJECTIVE: To determine the amount of torque expressed by various self-ligating brackets and to evaluate the influence of active clip designs. MATERIALS AND METHODS: Torque moments were measured for nine different bracket types in combination with a 0.019 * 0.025 inch stainless-steel archwire. All active brackets were measured in an open and a closed configuration to evaluate the influence of the self-ligating spring clip. In addition, slot dimensions were optically measured and compared to the torque expression. RESULTS: Moments between 3.1 Nmm and 22.6 Nmm were observed at an angulation of 30 degrees between archwire and slot. The amount of torque contributed by the spring clip of active self-ligating brackets was approximately 1 Nmm; 10 Nmm of torque was achieved with most brackets with a 20 degrees -25 degrees angulation between archwire and slot. The slot dimensions ranged from 0.0222 inch (0.563 mm) to 0.0241 inch (0.613 mm). CONCLUSION: The influence of the ligature or the active or passive self-ligating mechanism is minimal, and slot dimensions are far more important for the transmission of torque. The amount of torque exerted by the active spring clip is approximately 1/10th of the torquing moments recommended in the literature. PMID- 22059469 TI - Selective molecular sequestration with concurrent natural product functionalization and derivatization: from crude natural product extracts to a single natural product derivative in one step. AB - A resin-bound nitroso compound sequestered a single unexpected component from crude plant seed extracts. Several plants, including Piper nigrum, Eugenia caryophyllata, and Pimenta dioica, were extracted with organic solvent in the presence of a nitroso-containing resin. The nitroso resin selectively sequestered a single compound, beta-caryophyllene, via a chemo- and regioselective ene reaction. The ene product was released from the resin, and proper selection of the solid-phase linker and cleavage cocktail allowed concomitant further transformation of the primary ene product to a novel functionalized polycycle. Preliminary studies indicate that the new hydroxylamine-containing natural product derivatives have antibiotic activity. PMID- 22059470 TI - Iridium-catalyzed allylic fluorination of trichloroacetimidates. AB - A rapid allylic fluorination method utilizing trichloroacetimidates in conjunction with an iridium catalyst has been developed. The reaction is conducted at room temperature under ambient air and relies on Et(3)N.3HF reagent to provide branched allylic fluorides with complete regioselectivity. This high yielding reaction can be conducted on a multigram scale and shows considerable functional group tolerance. The use of [(18)F]KF.Kryptofix allowed (18)F(-) incorporation in 10 min. PMID- 22059475 TI - Evaluating correlation-based metric for surrogate marker qualification within a causal correlation framework. AB - Biomarkers play an increasing role in the clinical development of new therapeutics. Earlier clinical decisions facilitated by biomarkers can lead to reduced costs and duration of drug development. Associations between biomarkers and clinical endpoints are often viewed as initial evidence supporting the intended purpose. As a result, even though it is widely understood that correlation is not proof of a causal relationship, correlation continues to be used as a metric for biomarker qualification in practice. In this article, we introduce a causal correlation framework where two different types of correlations are defined at the individual level. We show that the correlation estimate is a composite of different components, and needs to be interpreted with caution when used for biomarker qualification to avoid misleading conclusions. Otherwise, a significant correlation can be concluded even in the absence of a true underlying association. We also show how the causal quantities of interest are testable in a crossover design and provide discussion on the challenges that exist in a parallel group setting. PMID- 22059476 TI - Bleeding and first-year mortality following hip fracture surgery and preoperative use of low-dose acetylsalicylic acid: an observational cohort study. AB - BACKGROUND: Hip fracture is associated with high mortality. Cardiovascular disease and other comorbidities requiring long-term anticoagulant medication are common in these mostly elderly patients. The objective of our observational cohort study of patients undergoing surgery for hip fracture was to study the association between preoperative use of low-dose acetylsalicylic acid (LdAA) and intraoperative blood loss, blood transfusion and first-year all-cause mortality. METHODS: An observational cohort study was conducted on patients with hip fracture (cervical requiring hemiarthroplasty or pertrochanteric or subtrochanteric requiring internal fixation) participating in a randomized trial that found lack of efficacy of a compression bandage in reducing postoperative bleeding. The participants were 255 patients (>=50 years) of whom 118 (46%) were using LdAA (defined as <=320 mg daily) preoperatively. Bleeding variables in patients with and without LdAA treatment at time of fracture were measured and blood transfusions given were compared using logistic regression. The association between first-year mortality and preoperative use of LdAA was analyzed with Cox regression adjusting for age, sex, type of fracture, baseline renal dysfunction and baseline cardiovascular and/or cerebrovascular disease. RESULTS: Blood transfusions were given postoperatively to 74 (62.7%) LdAA-treated and 76 (54%) non-treated patients; the adjusted odds ratio was 1.8 (95% CI 1.04 to 3.3). First year mortality was significantly higher in LdAA-treated patients; the adjusted hazard ratio (HR) was 2.35 (95% CI 1.23 to 4.49). The mortality was also higher with baseline cardiovascular and/or cerebrovascular disease, adjusted HR 2.78 (95% CI 1.31 to 5.88). Patients treated with LdAA preoperatively were significantly more likely to suffer thromboembolic events (5.7% vs. 0.7%, P = 0.03). CONCLUSIONS: In patients with hip fracture (cervical treated with hemiarthroplasty or pertrochanteric or subtrochanteric treated with internal fixation) preoperative use of low-dose acetylsalicylic acid was associated with significantly increased need for postoperative blood transfusions and significantly higher all-cause mortality during one year after surgery. PMID- 22059477 TI - In-house validation of PremiTest, a microbiological screening test with solvent extraction, for the detection of antimicrobial residues in poultry muscles. AB - PremiTest, a microbial inhibition test for the screening of antimicrobial residues, was validated according to the criteria established by Decision 2002/657/EC. Sensitivity, detection capability (CCbeta), specificity, selectivity, robustness and applicability were evaluated. The methodology involves the technique of solvent extraction, which increases the detection capability of the test for a wider range of antibiotics. The following CCbeta values in poultry muscle were found: penicillin G <= 12.5 ug kg(-1), total sulfonamides <= 75 ug kg(-1), erythromycin 75 ug kg(-1) and lincomycin 50 ug kg( 1). The detection capability of chlortetracycline was equal to its maximum residue limit (100 ug kg(-1)) and the method did not detect gentamicin (1000 ug kg(-1)), for which no MRL is established in poultry muscle. Specificity evaluated in relation to different analytes and matrices did not detect any interferences in the tests results; whilst the robustness showed that the pH neutralisation point of the extract affects the analytical results and the kits' performance. Only the screening of tetracyclines requires the analysis of extracts without pH neutralisation. The results of the validation process showed that this method is acceptable for screening beta-lactam, sulfonamide and macrolide antimicrobial groups in the National Residues and Contaminants Control Programme (PNCRC), and that for this it is fit for purpose. PMID- 22059478 TI - Activities identification for activity-based cost/management applications of the diagnostics outpatient procedures. AB - One of the most challenging problems facing healthcare providers is to determine the actual cost for their procedures, which is important for internal accounting and price justification to insurers. The objective of this paper is to find suitable categories to identify the diagnostic outpatient medical procedures and translate them from functional orientation to process orientation. A hierarchal task tree is developed based on a classification schema of procedural activities. Each procedure is seen as a process consisting of a number of activities. This makes a powerful foundation for activity-based cost/management implementation and provides enough information to discover the value-added and non-value-added activities that assist in process improvement and eventually may lead to cost reduction. Work measurement techniques are used to identify the standard time of each activity at the lowest level of the task tree. A real case study at a private hospital is presented to demonstrate the proposed methodology. PMID- 22059479 TI - Identification of interleukin-1 receptor-associated kinase 1 as a critical component that induces post-transcriptional activation of IkappaB-zeta. AB - IkappaB-zeta, an essential inflammatory regulator, is specifically induced by Toll-like receptor ligands or interleukin (IL)-1beta by post-transcriptional activation mediated via a 165-nucleotide element in IkappaB-zeta mRNA. Here, we analyzed the Toll-like receptor-IL-1 receptor signaling components involved in the post-transcriptional regulation of IkappaB-zeta with mutated estrogen receptor [ER(T2)] fusion proteins. Upon 4-hydroxytamoxifen treatment, the ER(T2) fusion proteins with IL-1 receptor-associated kinase (IRAK)1 and IRAK4 elicited specific activation of a reporter gene for the post-transcriptional regulation of IkappaB-zeta. The tumor necrosis factor receptor-associated factor (TRAF)6-ER(T2) protein activated nuclear factor-kappaB, but not post-transcriptional regulation, indicating that activation of IRAK1/4, but not of TRAF6, is sufficient to activate the 165-nucleotide element-mediated post-transcriptional mechanism. Interestingly, the post-transcriptional mechanism was not activated in TRAF6 deficient cells, indicating an essential role for TRAF6. Thus, the signaling pathway leading to nuclear factor-kappaB activation and the post-transcriptional activation bifurcates at IRAK1, suggesting a new pathway activated by IRAK1. PMID- 22059480 TI - Phylogenetic patterns in zopherine beetles are related to ecological niche width and dispersal limitation. AB - Niche conservatism has been proposed as the mechanism driving speciation in temperate montane clades through range fragmentation during climatic oscillations. Thus, a negative relationship between speciation rates and niche width is expected. Here, we test this prediction using American zopherine beetles. Our phylogenetic analyses recovered two clades in addition to that of the genus Zopherus: the genera Verodes and Phloeodes, which originated most likely in the Eocene, and diversified during the Miocene and the Pliocene. The assessment of clade niche width in relation to clade diversity supported the proposition of narrow niches leading to a higher probability of range fragmentation during climatic oscillations, thus increasing speciation. Additionally, almost all current populations of Phloeodes and Verodes are located within regions that retained favourable climatic conditions across warm and cold Pleistocene periods, suggesting that dispersal limitation is a strong factor controlling clade distribution. In sum, our results suggest that (i) niche width is a major determinant of the probability of speciation in temperate montane clades, by controlling the probability of potential range fragmentation and (ii) dispersal limitation is also a major determinant of the speciation process, by increasing the fragmentation of realized ranges even when potential distributions are cyclically fused during climatic oscillations. When dispersal limitation is extreme, as in zopherine beetles, populations persist just in those areas that have retained suitable conditions during extremes of past climatic oscillations. Paradoxically, this relict condition confers zopherine beetles great resilience for facing future climate change. PMID- 22059481 TI - Emergency preparedness for those who care for infants in developed country contexts. AB - Emergency management organisations recognise the vulnerability of infants in emergencies, even in developed countries. However, thus far, those who care for infants have not been provided with detailed information on what emergency preparedness entails. Emergency management authorities should provide those who care for infants with accurate and detailed information on the supplies necessary to care for them in an emergency, distinguishing between the needs of breastfed infants and the needs of formula fed infants. Those who care for formula fed infants should be provided with detailed information on the supplies necessary for an emergency preparedness kit and with information on how to prepare formula feeds in an emergency. An emergency preparedness kit for exclusively breastfed infants should include 100 nappies and 200 nappy wipes. The contents of an emergency preparedness for formula fed infants will vary depending upon whether ready-to-use liquid infant formula or powdered infant formula is used. If ready to-use liquid infant formula is used, an emergency kit should include: 56 serves of ready-to-use liquid infant formula, 84 L water, storage container, metal knife, small bowl, 56 feeding bottles and teats/cups, 56 zip-lock plastic bags, 220 paper towels, detergent, 120 antiseptic wipes, 100 nappies and 200 nappy wipes. If powdered infant formula is used, an emergency preparedness kit should include: two 900 g tins powdered infant formula, 170 L drinking water, storage container, large cooking pot with lid, kettle, gas stove, box of matches/lighter, 14 kg liquid petroleum gas, measuring container, metal knife, metal tongs, feeding cup, 300 large sheets paper towel, detergent, 100 nappies and 200 nappy wipes. Great care with regards hygiene should be taken in the preparation of formula feeds. Child protection organisations should ensure that foster carers responsible for infants have the resources necessary to formula feed in the event of an emergency. Exclusive and continued breastfeeding should be promoted as an emergency preparedness activity by emergency management organisations as well as health authorities. The greater the proportion of infants exclusively breastfed when an emergency occurs, the more resilient the community, and the easier it will be to provide effective aid to the caregivers of formula fed infants. PMID- 22059482 TI - Getting the most from pleural fluid analysis. AB - Virtually, every pulmonary disease and most non-pulmonary diseases may be associated with a pleural effusion. The presence of a pleural effusion allows the clinician to 'diagnose' or narrow the differential diagnosis and aetiology of the fluid collection. However, pleural fluid analysis (PFA) in isolation rarely provides a definitive diagnosis. This review discusses the rationale for evaluating patients with a pleural effusion. If the clinician obtains a detailed history, performs a comprehensive physical examination, reviews pertinent blood tests, and evaluates the chest imaging findings prior to thoracentesis, there should be a high likelihood of establishing a firm clinical diagnosis based on the appropriate PFA. This manuscript reviews the clinical presentation, chest imaging findings, duration and natural course of specific pleural effusions to help narrow the range of pre-thoracentesis diagnoses. A diagnosis of transudative effusion confirms an imbalance in hydrostatic and oncotic pressures, normal pleura and a limited differential diagnosis, which is typically apparent from the clinical presentation. Exudates are the result of infections, malignancies, inflammation, impaired lymphatic drainage or the effects of drugs, and pose a greater diagnostic challenge. The differential diagnosis for a pleural exudate can be narrowed if LDH levels exceed 1000 IU/L, the proportion of lymphocytes is >=80%, pleural fluid pH is <7.30 or there is pleural eosinophilia of >10%. PMID- 22059483 TI - The components of the putative iron transport system in the cyanobacterium Anabaena sp. PCC 7120. AB - Iron uptake in Gram-negative bacteria involves four distinct steps: (i) siderophore synthesis, (ii) siderophore secretion into the extracellular space, (iii) iron chelation by the siderophores, and (iv) siderophore/iron uptake via complexes in the outer membrane and the intermembrane space as well as in the plasma membrane. This process is well characterized for some proteobacterial systems, but largely unexplored and scarcely investigated in cyanobacteria such as the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120. Two putative siderophore synthesis clusters have been recently identified in this cyanobacterium. In addition, the export system for the main siderophore, schizokinen, secreted by Anabaena sp. PCC 7120 was described as well as the outer membrane transporter for its import from the extracellular space. We present the identification of components of three additional systems involved in siderophore mediated iron uptake under iron-limiting conditions, namely TonB3, the ExbB3/ExbD3 and the Fhu systems. The transcription level of these genes is elevated under iron limitations and decreased under excess iron, while the expression levels of other members of these gene families and systems are impacted in distinct ways by other environmental conditions. Mutants of the tonB3, exbB3/exbD3 and fhu genes show an iron starvation phenotype. Thus, Anabaena sp. has a similar, yet distinct system for siderophore-dependent iron uptake compared with other proteobacteria. PMID- 22059484 TI - Don't worry, be active: positive affect and habitual physical activity. AB - OBJECTIVE: The aim of ths study was to examine the association between habitual physical activity and positive and negative affect. METHOD: This cross-sectional study included 276 women aged 20 +, from the Geelong Osteoporosis Study. Habitual physical activity and other lifestyle exposures were assessed by questionnaire, concurrent with anthropometric assessments. Physical activity was categorized as very active, moderately active or sedentary. Positive and negative affect scores were derived from the validated 20 item Positive and Negative Affect Schedule (PANAS) self-report and were categorized into tertiles. RESULTS: There was a pattern of lower positive affect scores for lower levels of physical activity. With very active as the reference category, the odds for having a positive affect score in the highest tertile were sequentially lower for those who were moderately active (OR = 0.53, 95%CI 0.28-1.01) and sedentary (OR = 0.28, 95%CI 0.10-0.75). Associations were sustained after adjusting for body mass index and polypharmacy (OR = 0.50, 95%CI 0.26-0.96 and OR = 0.25, 95%CI 0.09-0.72, respectively). These associations were not explained by age, negative affect score or other exposures. No association was detected between physical activity and negative affect scores. CONCLUSIONS: This study reports that higher positive affect scores, encompassing emotions such as interest, excitement, enthusiasm and alertness, are associated with higher levels of habitual physical activity. These observations warrant further investigations into possible mechanistic interplay between neurobiological and psychosocial factors that underpin this association. PMID- 22059485 TI - In vitro absorption of dietary trans-resveratrol from boiled and roasted peanuts in Caco-2 cells. AB - Previous studies on the transport and absorption of resveratrol (3,5,4-O trihydroxystilbene) were done using the pure compound. In this study, the absorption of resveratrol in digested peanut micellar from boiled and roasted peanuts was investigated using a human intestinal Caco-2 cell monolayer. The amount transported and rate of transport of both resveratrol glycosides and its hydrolytic product were quantified by a reverse-phase high-performance liquid chromatography method with mass spectrometric detection. Four peaks were identified in the digested peanut micellar of both boiled and roasted peanuts: two resveratrol glycosides, one resveratrol diglycoside, and possibly an acylated resveratrol glycoside. Resveratrol from roasted peanut micellar had a higher transport rate than those from the boiled peanut. This implies that resveratrol from roasted peanut is better absorbed than from boiled peanut. Also, the rate of transport and amount of resveratrol transported were higher for the hydrolytic product than the nonhydrolyzed glycosides. This has strong implications for in vivo absorption as the enzymatic activity of gut microflora could enhance the bioavailability of beta-glycosides of dietary polyphenols. PMID- 22059486 TI - Effect of landiolol hydrochloride, an ultra-short-acting beta 1-selective blocker, on supraventricular tachycardia, atrial fibrillation and flutter after pulmonary resection. AB - WHAT IS KNOWN AND OBJECTIVE: Supraventricular tachycardia is a common complication after pulmonary resection. The objective of this study was to investigate the efficacy of landiolol hydrochloride, an ultra-short-acting beta1 blocker, in patients with post-operative supraventricular tachycardia after pulmonary resection. METHODS: The response to continuous intravenous infusion of landiolol was evaluated in 25 patients who developed post-operative atrial fibrillation or atrial flutter after major pulmonary resection. Four patients had preoperative rate-controlled chronic atrial fibrillation. The heart rate and blood pressure were compared before and after infusion of landiolol. Side effects and recurrence of supraventricular tachycardia after termination of landiolol infusion were also monitored. RESULTS AND DISCUSSION: The heart rate was reduced from 135+/-24 bpm before landiolol infusion to a plateau rate of 85+/-19 bpm during infusion (P<0.0001). Heart rate reduction occurred in all but two patients. Conversion to normal sinus rhythm from supraventricular tachycardia occurred in 14 patients (56%). Recurrence of supraventricular tachycardia after stopping landiolol infusion was observed in 17 patients (68%), but all patients without preoperative AF were cured of post-operative AF. There were no detectable side effects, including no adverse influence on the circulatory and respiratory systems. WHAT IS NEW AND CONCLUSION: Continuous intravenous infusion of landiolol was found to be effective and safe for supraventricular tachycardia after pulmonary resection. PMID- 22059487 TI - The DinB superfamily includes novel mycothiol, bacillithiol, and glutathione S transferases. AB - The superfamily of glutathione S-transferases has been the subject of extensive study; however, Actinobacteria produce mycothiol (MSH) in place of glutathione, and no mycothiol S-transferase (MST) has been identified. Using mycothiol and monochlorobimane as substrates, an MST activity was detected in extracts of Mycobacterium smegmatis and purified sufficiently to allow identification of MSMEG_0887, a member the DUF664 family of the DinB superfamily, as the MST. The identity of the M. smegmatis and homologous Mycobacterium tuberculosis (Rv0443) enzymes was confirmed by cloning, and the expressed proteins were found to be active with MSH but not bacillithiol (BSH) or glutathione (GSH). Bacillus subtilis YfiT is another member of the DinB superfamily, but this bacterium produces BSH. The YfiT protein was shown to have S-transferase activity with monochlorobimane when assayed with BSH but not with MSH or GSH. Enterococcus faecalis EF_3021 shares some homology with MSMEG_0887, but En. faecalis produces GSH but not MSH or BSH. Cloned and expressed EF_0321 was active with monochlorobimane and GSH but not with MSH or BSH. MDMPI_2 is another member of the DinB superfamily and has been previously shown to have mycothiol-dependent maleylpyruvate isomerase activity. Three of the eight families of the DinB superfamily include proteins shown to catalyze thiol-dependent metabolic or detoxification activities. Because more than two-thirds of the sequences assigned to the DinB superfamily are members of these families, it seems likely that such activity is dominant in the DinB superfamily. PMID- 22059488 TI - Multifunctional gold-silica nanostructures for ultrasensitive electrochemical immunoassay of streptomycin residues. AB - A facile and simple electrochemical immunoassay for ultrasensitive determination of streptomycin residues (STR) in food was designed by using nanogold-assembled mesoporous silica (GMSNs) as bionanolabels on a three-dimensional redox-active organosilica-functionalized sensing interface. To construct such a sensing interface, we initially synthesized organosilica colloids by using wet chemical method, and then utilized the prepared colloidal organosilica nanocomposites for the immobilization of monoclonal anti-STR antibodies on a glassy carbon electrode based on a sol-gel method. The bionanolabels were prepared based on coimmobilization of horseradish peroxidase (HRP) and STR-bovine serum albumin conjugates (STR-BSA) on the GMSNs. With a competitive-type immunoassay format, the assay toward STR analyte was carried out in pH 5.5 acetate acid buffer (ABS) by using redox-active organosilica nanocomposites as electron mediators, biofunctionalized GMSNs as traces, and hydrogen peroxide (H(2)O(2)) as enzyme substrate. Under optimal conditions, the reduction current of the electrochemical immunosensor decreased with the increase in STR level in the sample, and displayed a wide dynamic range of 0.05-50 ng mL(-1) with a low detection limit (LOD) of 5 pg mL(-1) at 3s(B). Intra- and interassay coefficients of variation were less than 8.7 and 9.3% for STR detection, respectively. In addition, the methodology was validated with STR spiked samples including honey, milk, kidney, and muscle, receiving a good correspondence with the results obtained from high performance liquid chromatography (HPLC). PMID- 22059489 TI - Enzyme-linked bridging assay method for the quantification of oligonucleotide based drugs in biological matrices. AB - With ongoing efforts to develop oligonucleotide-based (ODN-based) therapeutics, there is a need for a sensitive, high-throughput method of quantification of ODN based drugs in biological matrices. To overcome the insufficient sensitivity and time-consuming sample extraction procedures involved in conventional capillary gel electrophoresis (CGE) and high-performance liquid chromatography (HPLC), we developed a nucleic acid hybridization-based enzyme-linked bridging assay (ELBA), which shows significant advantages over CGE methods in evaluating ODN-based drugs in plasma and tissue: (1) It has higher sensitivity; (2) it involves easier sample extraction procedures; (3) it is suitable for many ODN-based drugs, even those with different secondary structures and modifications, including phosphorothioate oligonucleotide (PSODN), mixed backbones with 2'-O-Me (MBO), locked nucleic acid (LNA) modifications, and B- and C-type CpG sequences; and (4) it is highly selective, even during simultaneous quantification, with regard to intact ODNs and their 3'-metabolites. This universal design produces a rapid, sensitive, specific assay with minimal method development time. It is well suited to high-throughput analysis of various ODN-based drugs. PMID- 22059490 TI - D-pi-A-A-pi-D prototype 2,2'-bipyridine dyads exhibiting large structure and environment-sensitive fluorescence: synthesis, photophysics, and computation. AB - A series of 4,4'-pi-conjugated-2,2'-bipyridine chromophores (MS 1-8) were synthesized, and their photophysical and thermal properties were investigated. The title "push-pull' chromophores", except MS 1, were integrated with both alkoxy and alkylamino donor functionalities that differ in their donation capabilities. The oligophenylenevinylene (OPV) chromophores MS 4-8 are associated with a pi-extended backbone in which the position and the number of alkoxy donors were systematically varied. All of the studied systems possess a D-pi-A-A-pi-D dyad archetype in which the A-A is the central 2,2'-bipyridine acceptor core that is electronically attached with the donor termini through pi-linkers. The fluorescence quantum yields of the synthesized chromophores are found to be sensitive to the molecular archetype and the solvent medium. Out of the eight fluorescent compounds reported in this article, the compound MS 5 exhibits fluorescence in the solid state also. The modulating effect of the nature, position, and number of donor functionalities on the optical properties of these classes of compounds has further been comprehended on the basis of DFT and TD-DFT computation in a solvent reaction field. PMID- 22059491 TI - Changes in carcass and meat quality traits of Danish friesian cull cows with the increase of their age and body condition. AB - Data from 98 Danish cull cows were used in this study. Cows were divided into three age groups: 'very young' (<3 years), 'young' (3-5 years) and 'mature' (>4.5 years) and three body condition classes: 'thin', 'normal' and 'fat'. Independent of body condition, age had no significant effect on carcass scores related to conformation or to fatness. However, as the cow dvances in age, the carsass (lean and fat) colour tends to become darker yellow and the longissimus dorsi has a greater area with thicker cover-fat. Meat quality appeared to be independent of age with regards to its colour-related traits and its content of dry matter and intramuscular fat. However, the meat showed an increase in shear force value with age. Independent of age, the classification of cows according to their condition score prior to slaughter revaled significant differences in the quality of carcass and meat. While passing from 'thin' to 'normal' then to 'fat' condition, the carcasses showed better conformation score, a darker yellow colour, higher score of fatness and larger longissimus dorsi area with thicker cover-fat. The mean from 'fat' cows had similar shear force. PMID- 22059492 TI - An assessment of simple referee methods for the prediction of lean in pig carcasses. AB - A study was carried out in which carcass characteristics of 36 gilts were evaluated: 18 originated from the Hungarian 'Hungahyb' cross-breed, another 18, with undefined genetic background, from small private household plots. Two, rather simple substitute reference methods, called referee methods, were evaluated: measurement of carcass weight without skin and subcutaneous fat ('meat + bone'), and measurement of carcass weight without skin, subcutaneous fat and bone ('boneless meat'). Both methods gave a rather close relationship with the Kulmbach reference lean; however, removal of bone had presumably a beneficial effect on stability of prediction. The importance of preliminary information in quantitative form, giving a theoretical background for prediction equations, was presented as an example. Simple material balances could be formulated between reference lean and 'meat + bone' or 'boneless meat' content. Such material balances could not be set up with the indirect, rapid surrogate methods using mainly linear measurements (e.g. fat and muscle thickness, etc.) For this reason, as several other publications demonstrated, these latter methods seem to be more susceptible to bias than the referee methods. By determining the lipid content of the homogenised 'boneless meat' component, a 'lean' value adjusted to 3% fat content could be calculated from data which was compared to the dissected reference lean standardised also to contain 3% fat. These relationships, for several reasons discussed in this paper, were not as close as expected. So, further studies are needed to reveal these discrepancies. PMID- 22059493 TI - Effect of oral loading of acid or base on the incidence of pale soft exudative pork (PSE) in stress-susceptible pigs. AB - Thirty-three halothane-positive pigs were assigned to one of three ad libitum water treatments 4 days prior to slaughter: control, sodium bicarbonate (12.6 g litre(-1)), or ammonium chloride (8 g litre(-1)) to study the effect of an oral acid or base load on post-mortem changes in the longissimus dorsi muscle and on ultimate pork quality. Eight halothane-negative pigs were also slaughtered as negative controls. Dietary ammonium chloride caused a metabolic acidosis as indicated by lower blood and urine pH, and lower blood bicarbonate in treated pigs. In halothane-positive pigs, dietary treatments had no significant effect on post-mortem muscle pH changes or on measurements of muscle quality (colour, drip loss, texture scores or protein solubility). There was a weak to modest relationship between the blood gas measurements and meat quality indicators. Blood pH (r = 0.566) and bicarbonate (r = 0.514) were positively correlated with subjective texture scores and a trend was seen for blood PCO(2) and bicarbonate to be positively related to 45 min pH and subjective colour. These observations suggest that pigs with increased blood pH and bicarbonate may show an improvement in meat quality. Further research is necessary to find the optimum time and level of treatment to maximize the response. PMID- 22059494 TI - Evaluation of Longissimus dorsi muscle pH at three hours Post mortem as a predictor of beef tenderness. AB - The objective of this study was to determine the relationship of beef longissimus dorsi muscle (LM) pH at 3 h post mortem (pH(3)) and aged LM tenderness. The cattle (n = 444) sampled for this experiment represented various breed types, sex classes, feeding regimes, and post-mortem handling practices. The phenotypic diversity of the cattle used provided a great amount of variation in Warner Bratzler shear (WBS) force (Coefficient of variation for pH, temperature, and sarcomere length measurements were much smaller than the coefficient of variation for WBS force). None of the parameters measured (LM pH at 3 and 48 h post mortem, temperature at 3 h post mortem and sarcomere length) was strongly related to tenderness. These results do not support the use of pH(3) as a criterion for sorting beef carcasses into expected tenderness groups. PMID- 22059495 TI - Effect of oxidized dietary lipid and vitamin E on the colour stability of pork chops. AB - The effect of oxidized corn oil and vitamin E (alpha-tocopheryl acetate) in pig diets on the oxidative stability of muscle lipids and on the surface colour characteristics of fresh and previously frozen pork chops in refrigerated storage was investigated. Lipid oxidation (TBARS values) and surface redness (Hunter 'a' values) were significantly influenced (P < 0.01) by dietary alpha-tocopheryl acetate levels but not by degree of oxidation of dietary corn oil. Lipid oxidation and colour deterioration during refrigerated storage were greater in previously frozen chops compared to fresh chops. TBARS values were lower and Hunter 'a' values higher in pork chops from pigs fed 100 and 200 mg alpha tocopheryl acetate/kg diet compared to pigs fed 10 mg/kg diet after 2, 4, 6 and 8 days of refrigerated storage. Hunter 'a' values were significantly correlated (P < 0.01) with the logarithm of TBARS values. The results suggest that oxidation of myoglobin precedes oxidation of muscle lipids in pork chops stored at 4 degrees C. PMID- 22059496 TI - Hydrolysis and loss of extractability of proteins during ripening of iberian ham. AB - To elucidate the extent of the hydrolysis and loss of extractability of protein during the traditional ripening of Iberian ham, the evolution during processing of non-protein nitrogen (NPN) and protein fractions soluble in 0.03 m pH 7.1 phosphate and 1.1 KI + 0.1 m phosphate pH 7.4 buffers and 6 m urea was followed from Semimembranosus and Biceps femoris muscles. The NPN steadily increased during processing, showing maximum intensity at salting and drying. Electrophoretic study of the proteins extracted, and microscopical examination of the pellet obtained after consecutive extractions with the above buffers, revealed that hydrolysis and insolubilization are more intense in myofibrillar than in sarcoplasmic proteins. Protein aggregation involves mainly the myofibrillar fraction, and occurs during the first stage of processing. PMID- 22059497 TI - Relations between compositional traits and sensory qualities of French dry-cured ham. AB - The left hams of 20 pig carcasses were processed by dry-curing for either 179 (n = 10) or 273 days (n = 10). The Biceps femoris was taken at the end of the processing and submitted to chemical and sensory analyses. The following chemical traits were determined: pH, moisture, salt content, fatty acid content and composition of lipid classes (triglycerides, phospholipids, free fatty acids), nitrogen fractions (soluble and insoluble protein, non-protein nitrogen, free amino acids) and volatile compounds. Sensory analysis was performed by a panel of 12 trained members, who scored texture traits (firmness, dryness, fibrousness, mellowness), taste (salty, acid), intensity of aromas (typical of dry ham, fresh meat, fat, cured meat, rancid, metal), persistence of dry ham aroma, persistence of taste after deglutition, persistence of astringency, persistence of metallic taste. The sensory qualities of dry-cured ham showed noticeable changes between days 179 and 273. Firmness, dryness and intensities of aromas typical of dry cured ham and cured meat were enhanced with time. Neither pH, moisture nor salt content played a noticeable role in determining the sensory quality of dry-cured ham. Among the volatile compounds, the levels of several ketones and 1-butanol were significantly correlated with the aromas of dry ham and cured meat, while rancid aroma was related to aldehydes, ethylacetate, 2,3-pentanedione and nonane. Therefore, the aromas of dry ham and cured meat appeared to be determined mainly by the products of lipid oxidation. However, they were related also to unidentified volatile compounds, whose identification would be of particular interest. PMID- 22059498 TI - Time-related changes in intramuscular lipids of French dry-cured ham. AB - The aim of this study was to investigate the changes in intramuscular lipids during the processing of French dry-cured hams. In the fresh biceps femoris muscle, the lipid content was on average, 105 mg/g DM with a large individual variation. Glycerides accounted for about 75% of total lipids. During processing for 273 days, phospholipid content decreased markedly whereas free fatty acid content rose from 1.9 mg/g DM to 9.4 mg/g DM. Little change affected the fatty acid composition of both glycerides and phospholipids during processing. After a decrease in the proportion of polyunsaturated fatty acids during the first 2 months, free fatty acid composition remained stable. The results suggest that lipid alteration during dry-curing of hams is due to lipolysis and that lipid oxidation is limited. PMID- 22059499 TI - Effects of distribution packaging method and storage time on the physical properties and retail display characteristics of pork. AB - The sensory characteristics of pork chops from bone-in loins and Boston butts (n = 65 each) were affected little by primal loin and the butt packaging method (paper wrap, vacuum pack and gas flush) and storage time (7, 10 and 14 days) under industry conditions. However, loin chops fabricated from vacuum-packaged loins after 14 days of storage had less (P < 0.05) discoloration and two-toning than chops fabricated from other loins. All loin chops were placed in retail display and overwrapped with a polyvinyl chloride film after fabrication at each storage time. Vacuum-packed butts stored for 10 and 14 days produced chops with less discoloration and two-toning, and higher overall appearance scores (P < 0.05) compared to chops from paper-wrapped or gas-flushed cuts. Vacuum-packaging resulted in higher quality retail cuts than paper-wrapped or gas-flushed packaging. Thus, it is recommended that the pork industry and retail distribution system utilize vacuum-packaging as the primary method to store and ship fresh pork before retail sale. PMID- 22059500 TI - The effect of acidification on myofibrillar proteins. AB - Isolated myofibrillar proteins of mutton, beef and chicken were treated with an acidulent to give various pH values and stored at 5 degrees C for 20 h before analysing the proteins using sodium dodecylsulphate polyacrylamide gel electrophoresis. It was found that protein degradation occurred below pH 4.5, with a decrease in band intensity of all major myofibrillar proteins, particularly myosin heavy chain, and the appearance of new bands at approximately 140 and 70 kd. The degradation had an optimum around pH 3.0 and was inhibited by a high temperature pre-treatment or the presence of the endopeptidase inhibitors pepstatin A and leupeptin. Results are discussed in terms of the action of acid proteinase enzymes. PMID- 22059501 TI - The display of retail packs of ground beef after their storage in master packages under various atmospheres. AB - Batches of coarsely ground beef trimmings were each divided into four portions. One portion from each batch was vacuum packaged, then stored at -1.5 degrees C. The other portions were finely ground and distributed in retail packs. The retail packs were master packaged under atmospheres of N(2), CO(2) or O(2) + CO(2) (2:1, v/v), then stored at 2 degrees C. The product was assessed after storage times of up to 32 days. For each assessment, a vacuum pack and a master pack of each type, each containing products from the same batch, were withdrawn from storage. The vacuum packaged product was finely ground and distributed into retail packs. The newly prepared retail packs and those from the master packs were displayed in a retail cabinet in which air temperatures averaged 4 +/- 2 degrees C. The appearance of the displayed product from each storage packaging was assessed twice daily until it was judged to be unacceptable. At the beginning and end of the display, the product in each pack was assessed for discoloration and off odours, the chemical states of the muscle pigment at the exposed surface were estimated, and the surface microflora was characterized. The appearance of the product displayed after storage in a vacuum pack, for times up to 32 days, became unacceptable within 48 h. A product stored in any of the master packs for 1 day appeared unacceptable after 6 h of display. The display life of products stored under N(2) or CO(2) was similar to that of the vacuum packaged products when storage times were between 2 and 24 days but the display life was shorter when the storage times were 28 or 32 days. The display life of products stored under O(2) + CO(2) was similar to that of the vacuum packaged product when storage times were 2, 4 or 6 days, but the appearance of products stored under O(2) + CO(2) for 8 days or longer was unacceptable when master packs were opened. Apart from those latter packs, a product was not discoloured when storage packs were opened. However, all products were discoloured, and the metmyoglobin fractions of the surface pigments had increased, when the product was withdrawn from display. The products in all storage packagings developed flora dominated by lactic acid bacteria. The spoiage flora on products stored in vacuum pack or under O(2) + CO(2) did not attain the maximum numbers of 10(7)/g during either storage or display. Those maximum numbers were attained on products stored under N(2) and CO(2) after 16 and 28 days storage respectively. Some products stored under N(2) for 16 days or longer developed moderate or strong off-odours during display that were ascribable to microbial action. Other products developed only slight, non microbial off-odours during display. Retail-ready packs or ground beef master packaged under an oxygen-depleted atmosphere could then have a useful storage life of about 30 days in commercial circumstances. PMID- 22059502 TI - Pyridinoline in ovine intramuscular collagen. AB - Pyridinoline, a mature crosslink of collagen, was measured in intramuscular connective tissue isolated from ovine semimembranosus, a muscle noted for its highly insoluble collagen. Concentration ranged between 0.25 and 0.59 mol/mol of collagen, on the high side of concentrations reported in the literature for this and other muscles in various species. Pyridinoline concentration was inversely related to collagen solubility in muscle homogenates (P < 0.0). In a comparison between semimembranosus, biceps femoris and gluteus medius, pyridinoline concentration was again inversely related to collage solubility. For all these muscles, pyridinoline remained insoluble in a heat-dependent solubility test, but it is argued that pyridinoline does not explain all the solubility properties of ovine intramuscular collagen. Pyridinoline concentration was not significantly correlated with sensory or shear properties of cooked semimembranosus, confirming the importance of other heat-stable crosslinks. PMID- 22059503 TI - Authentication of African green monkey cell lines using human short tandem repeat markers. AB - BACKGROUND: Tools for authenticating cell lines are critical for quality control in cell-based biological experiments. Currently there are methods to authenticate human cell lines using short tandem repeat (STR) markers based on the technology and procedures successfully used in the forensic community for human identification, but there are no STR based methods for authenticating nonhuman cell lines to date. There is significant homology between the human and vervet monkey genome and we utilized these similarities to design the first multiplex assay based on human STR markers for vervet cell line identification. RESULTS: The following STR markers were incorporated into the vervet multiplex PCR assay: D17S1304, D5S1467, D19S245, D1S518, D8S1106, D4S2408, D6S1017, and DYS389. The eight markers were successful in uniquely identifying sixty-two vervet monkey DNA samples and confirmed that Vero76 cells and COS-7 cells were derived from Vero and CV-1 cells, respectively. The multiplex assay shows specificity for vervet DNA within the determined allele range for vervet monkeys; however, the primers will also amplify human DNA for each marker resulting in amplicons outside the vervet allele range in several of the loci. The STR markers showed genetic stability in over sixty-nine passages of Vero cells, suggesting low mutation rates in the targeted STR sequences in the Vero cell line. CONCLUSIONS: A functional vervet multiplex assay consisting of eight human STR markers with heterozygosity values ranging from 0.53-0.79 was successful in uniquely identifying sixty-two vervet monkey samples. The probability of a random match using these eight markers between any two vervet samples is approximately 1 in 1.9 million. While authenticating a vervet cell line, the multiplex assay may also be a useful indicator for human cell line contamination since the assay is based on human STR markers. PMID- 22059504 TI - End-functionalized polymerization of 2-vinylpyridine through initial C-H bond activation of N-heteroaromatics and internal alkynes by yttrium ene-diamido complexes. AB - We successfully introduced end-capping functional groups to poly(2 vinylpyridine)s by initial introduction of the functional groups on yttrium catalysts through C-H bond activation of heteroaromatics and internal alkynes to the Y center via alkylyttrium-mediated sigma-bond metathesis. PMID- 22059505 TI - Muscle fibre characteristics and metabolic response at slaughter in pigs of different halothane genotypes and their relation to meat quality. AB - Muscle samples for histochemical and biochemical analyses were taken immediately at slaughter from M. longissimus dorsi of pigs with different halothane genotypes (NN and nn). Fibre type composition was similar between groups but the nn genotype had larger mean fibre areas and lower capillary density than the NN genotype. At exsanguination the nn-genotype had lower muscle pH (pH(e)), higher lactate and ammonia and lower glycogen and phosphagen (ATP and CP) concentrations and twice as many glycogen-depleted type IIA and IIB fibres as compared with the NN-genotype. Muscle pH(e) was correlated positively to capillary density, glycogen and phosphagen concentrations and negatively to mean fibre area, ammonia and lactate concentrations. Ammonia concentrations were correlated negatively to ATP concentrations and positively to the percentage of glycogen-depleted IIB fibres. The highest reflectance and drip loss values were seen in the nn genotype. The reflectance values were correlated positively to the percentage of glycogen-depleted type IIB fibres in muscle and the values for drip loss were correlated negatively to pH(e). These data show that fibre size and capillary density in muscle seem to be important factors that influence the metabolic response at slaughter and thus meat quality. PMID- 22059506 TI - The effects of preblending time on physical and textural properties of coarse ground sausages. AB - The effects of preblending storage time on physical and textural properties of coarse ground sausages were characterized. Raw materials (pork, beef) were preblended at 0-2 degrees C and held for 0, 4, 8, 12, 16, 48, 96, 144, 196 or 240 h just prior to manufacture into Polish sausages. Expressible moisture (EM), raw batter stability, processing yield (PY), Instron compression (CO) and protein solubilization (SEM micrographs) increased from 0 to 16 h. No differences were observed for EM, PY and CO and in SEM micrographs for the 48-240 h interval. The effects of storage of preblends on sausage physical and textural properties (raw batter stability, yield, cohesiveness, SEM micrographs) occurred rapidly (0-16h), reached a maximum and either remained constant or diminished as storage time increased from 48 to 240 h. PMID- 22059507 TI - Effect of processing and storage on neutral lipids of buffalo meat. AB - Three muscles viz. Triceps brachii (TB), Longissimus dorsi (LD) and Biceps femoris (BF) from different anatomical locations of adult male buffaloes were stored after broiling and pressure cooking under refrigerated (4 degrees C) condition for 3, 6, 9 days and 30, 60, 90 days under frozen (-10 degrees C) storage. At the end of each storage interval they were analysed for total lipids, cholesterol contents and glyceride fractions i.e. monoglycerides (MG), diglycerides (DG), and triglycerides (TG). Muscles differed significantly in total lipids as well as contents of all glyceride fractions. Muscle LD had significantly higher total lipid content than TB and BF. Muscles differed significantly in their esterfied cholesterol (EC) contents. Heat processing increased total lipids, cholesterol, MG, DG and TG contents of all the buffalo muscles studied. Total cholesterol contents remained unchanged during refrigerated and frozen storage. However, EC, MG, DG and TG contents declined during storage. The influence of anatomical locations on fatty acid composition of neutral lipids was observed. The ratio of unsaturated to saturated fatty acids increased due to cooking. A gradual decrease in mono- and polyunsaturated fatty acids was recorded during refrigerated and frozen storage. PMID- 22059508 TI - Collagen and its rational content in meat products: Part 1. Analytical studies. AB - Computer-assisted simulation has been used to study the effect of collagen content on the biological value of meat proteins. It has been shown that an increase in the collagen content from 2.5% to 15-20% of the total amount of proteins contained in minced meat tangibly enhances protein utilization for tissue synthesis. Hence, the above collagen content in meat products heightens their nutritional and biological value and renders them more suited for human metabolism. PMID- 22059509 TI - Physical, chemical and organoleptic characteristics of Turkish style frankfurters made with an emulsion containing Turkish soy flour. AB - The possibility of using Turkish Defatted Soy Flour (DSF) to replace part of the meat in Turkish style frankfurters was studied and the technological, physical, chemical, nutritional, sensory and quality characteristics of these sausages produced under Turkish conditions were determined. No significant difference in physical and sensory properties between the control group (all meat) and treatment groups (5, 10 and 20% soy flour) was found. DSF up to the level used significantly (P > 0.01) increased moisture and protein and decreased fat levels of the sausages. The amino acid and PER results also indicated that replacing meat with DSF in sausages did not significantly alter the nutritional value of the sausages. PMID- 22059510 TI - Modelling post-mortem tenderisation-I: Texture of electrically stimulated and non stimulated beef. AB - Texture in electrically stimulated and non-stimulated beef M Pectoralis profundus, stored under a range of temperatures from 0 to 30 degrees C, while avoiding muscle shortening, was measured from 1 to 21 days after stunning. The pre-rigor temperature (from 0 to 30 degrees C), maintained until the pH had fallen to 6.4 and then held at 15 degrees C, had no effect on the toughness nor on the rate of tenderisation after rigor. Modelling toughness prior to 24 h suggested that toughness of all muscles could be rationalised and that first order tenderisation began when the muscles reached pH 6.1 when the toughness of all the muscles was projected to be 12.5 kg. After pH 6.1, the rate of tenderisation at 30 degrees C was 10-fold higher than at 1 degrees C and was not affected by variations in pH from 6.1 to 5.5. At the higher temperatures, the ultimate toughness of aged meat was slightly higher than at the lower temperatures. PMID- 22059511 TI - Modelling post-mortem tenderisation-II: Enzyme changes during storage of electrically stimulated and non-stimulated beef. AB - Levels of calpains I and II, cathepsins B and L and beta-glucuronidase were determined in extracts of electrically stimulated and control beef M. Pectoralis profundus stored at temperatures between 0 and 30 degrees C and varied to avoid muscle shortening. The level of lysosomal enzymes remained essentially unchanged throughout storage. The levels of calpain II were largely unaffected by the early treatments and decreased slightly throughout ageing. The level of calpain I, in both stimulated and control meats, was unaffected by temperature prior to the attainment of about pH 6.2 and thereafter the loss was accelerated at higher temperatures. In the extreme case studied, that of stimulated meat held at 15 degrees C, 73% of the activity was lost in the first 24 h. After ageing, the level was about 11% of the initial when stored at 1 degrees C and 25% when stored at 15 degrees C. The exponential decay constants for the decrease in the levels of calpain I were 0.01 h(-1) at 1 degrees C and 0.06 h(-1) at 15 degrees C, and were the same as those for the previously determined rate of tenderisation. This suggested that the rate of proteolysis by calpain I was linked to the rate of tenderisation. PMID- 22059512 TI - Modelling post-mortem tenderisation-III: Role of calpain I in conditioning. AB - A simple model is developed to show how proteolysis by calpain I can account for the variations in tenderness in electrically stimulated and nonstimulated beef pectoralis profundus muscles stored between 0 degrees C and 30 degrees C. As the pH of the muscle falls to about 6.1, calpain I is activated and causes proteolysis and tenderisation. The rate of tenderisation is then proportional to the concentration of calpain I which is autolysed slowly reducing its concentration and the rate of tenderisation. The activation energy for the inactivation (autolysis) of calpain I is slightly higher than that for its activity in tenderisation (proteolysis) and therefore, at higher temperatures, less tenderisation occurs. Proteolysis and tenderisation continue at a rate governed by the concentration of calpain I and the temperature until calpain I is depleted when tenderisation stops. Parameters for the activity and inactivation of calpain I were derived and were shown to predict 68% of the variation in toughness. PMID- 22059513 TI - Effect of animal sex and size on effort when pelting lambs. AB - Pelting load data were collected and analysed for 304 lambs (comprising 46% ewes, 26% cryptorchids and 28% rams), all of which came from one farm. Although typically about 24% more impulse (Ns) had to be applied for pelting ram lambs than for ewe or cryptorchid lambs, only one-third of this increase was attributable to the distinct sexual category of rams; the rest was due to rams being heavier. Carcass size had a much greater effect on pelting load than animal sex: a change in dressed carcass weight of slightly less than 1 kg has the same effect on impulse requirement as the net sex effect. These findings suggest that the differences in pelting effort associated with animal sex are of relatively minor significance compared with the large differences occurring over the range of lamb size normally processed. PMID- 22059514 TI - Microstructural manifestations of two unusual phenomena detected in experimental roast pork: A scanning and transmission electron microscopy study. AB - Loin roasts L. dorsi from both barrows and gilts from a breeding and feeding experiment were cooked, cut, presented to sensory evaluation panelists and the excess meat stored at 4 degrees C in tied plastic bags. An interesting phenomenon observed was that a deposit remained on the cutter blade after slicing the experimental roasts, but no deposit remained in the blade after cutting control roasts. Similarly, slices of experimental roast adhered together after refrigeration, but slices of control roast stored under identical conditions did not stick together. Electron microscopic examination showed that the experimental samples were made up of three zones consisting of fat, collagen and muscle tissue. The thickness of the middle (collagen) zone varied with the sex of the animals and possibly with their genetic background. Where the experimental roast slices adhered, they always did so only at the middle collagen layer. In contrast, control samples were made up of only two layers: fat and muscle, with the collagen layer between them being absent or much reduced in thickness. PMID- 22059515 TI - Lipopolysaccharide-induced sickness behaviour evaluated in different models of anxiety and innate fear in rats. AB - The fact that there is a complex and bidirectional communication between the immune and nervous systems has been well demonstrated. Lipopolysaccharide (LPS), a component of gram-negative bacteria, is widely used to systematically stimulate the immune system and generate profound physiological and behavioural changes, also known as 'sickness behaviour' (e.g. anhedonia, lethargy, loss of appetite, anxiety, sleepiness). Different ethological tools have been used to analyse the behavioural modifications induced by LPS; however, many researchers analysed only individual tests, a single LPS dose or a unique ethological parameter, thus leading to disagreements regarding the data. In the present study, we investigated the effects of different doses of LPS (10, 50, 200 and 500 MUg/kg, i.p.) in young male Wistar rats (weighing 180-200 g; 8-9 weeks old) on the ethological and spatiotemporal parameters of the elevated plus maze, light-dark box, elevated T maze, open-field tests and emission of ultrasound vocalizations. There was a dose-dependent increase in anxiety-like behaviours caused by LPS, forming an inverted U curve peaked at LPS 200 MUg/kg dose. However, these anxiety like behaviours were detected only by complementary ethological analysis (stretching, grooming, immobility responses and alarm calls), and these reactions seem to be a very sensitive tool in assessing the first signs of sickness behaviour. In summary, the present work clearly showed that there are resting and alertness reactions induced by opposite neuroimmune mechanisms (neuroimmune bias) that could lead to anxiety behaviours, suggesting that misunderstanding data could occur when only few ethological variables or single doses of LPS are analysed. Finally, it is hypothesized that this bias is an evolutionary tool that increases animals' security while the body recovers from a systemic infection. PMID- 22059516 TI - Boechera Summit 2011. AB - Ecological model systems provide a conduit to understand the ecological impact of information gained from laboratory model species. Here, I review a 2011 meeting which focused on the systematic, ecological, evolutionary and developmental biology of the ecological model genus Boechera. PMID- 22059517 TI - Emotion expression in body action and posture. AB - Emotion communication research strongly focuses on the face and voice as expressive modalities, leaving the rest of the body relatively understudied. Contrary to the early assumption that body movement only indicates emotional intensity, recent studies have shown that body movement and posture also conveys emotion specific information. However, a deeper understanding of the underlying mechanisms is hampered by a lack of production studies informed by a theoretical framework. In this research we adopted the Body Action and Posture (BAP) coding system to examine the types and patterns of body movement that are employed by 10 professional actors to portray a set of 12 emotions. We investigated to what extent these expression patterns support explicit or implicit predictions from basic emotion theory, bidimensional theory, and componential appraisal theory. The overall results showed partial support for the different theoretical approaches. They revealed that several patterns of body movement systematically occur in portrayals of specific emotions, allowing emotion differentiation. Although a few emotions were prototypically expressed by one particular pattern, most emotions were variably expressed by multiple patterns, many of which can be explained as reflecting functional components of emotion such as modes of appraisal and action readiness. It is concluded that further work in this largely underdeveloped area should be guided by an appropriate theoretical framework to allow a more systematic design of experiments and clear hypothesis testing. PMID- 22059518 TI - Threat facilitates subsequent executive control during anxious mood. AB - Dual competition framework (DCF) posits that low-level threat may facilitate behavioral performance by influencing executive control functions. Anxiety is thought to strengthen this effect by enhancing threat's affective significance. To test these ideas directly, we examined the effects of low-level threat and experimentally induced anxiety on one executive control function, the efficiency of response inhibition. In Study 1, briefly presented stimuli that were mildly threatening (i.e., fearful faces) relative to nonthreatening (i.e., neutral faces) led to facilitated executive control efficiency during experimentally induced anxiety. No such effect was observed during an equally arousing, experimentally induced happy mood state. In Study 2, we assessed the effects of low-level threat, experimentally induced anxiety, and individual differences in trait anxiety on executive control efficiency. Consistent with Study 1, fearful relative to neutral faces led to facilitated executive control efficiency during experimentally induced anxiety. No such effect was observed during an experimentally induced neutral mood state. Moreover, individual differences in trait anxiety did not moderate the effects of threat and anxiety on executive control efficiency. The findings are partially consistent with the predictions of DCF in that low-level threat improved executive control, at least during a state of anxiety. PMID- 22059519 TI - Visual attention and emotional memory: recall of aversive pictures is partially mediated by concurrent task performance. AB - The emotional enhancement of memory is often thought to be determined by attention. However, recent evidence using divided attention paradigms suggests that attention does not play a significant role in the formation of memories for aversive pictures. We report a study that investigated this question using a paradigm in which participants had to encode lists of randomly intermixed negative and neutral pictures under conditions of full attention and divided attention followed by a free recall test. Attention was divided by a highly demanding concurrent task tapping visual processing resources. Results showed that the advantage in recall for aversive pictures was still present in the DA condition. However, mediation analyses also revealed that concurrent task performance significantly mediated the emotional enhancement of memory under divided attention. This finding suggests that visual attentional processes play a significant role in the formation of emotional memories. PMID- 22059520 TI - Can an anger face also be scared? Malleability of facial expressions. AB - Do people always interpret a facial expression as communicating a single emotion (e.g., the anger face as only angry) or is that interpretation malleable? The current study investigated preschoolers' (N = 60; 3-4 years) and adults' (N = 20) categorization of facial expressions. On each of five trials, participants selected from an array of 10 facial expressions (an open-mouthed, high arousal expression and a closed-mouthed, low arousal expression each for happiness, sadness, anger, fear, and disgust) all those that displayed the target emotion. Children's interpretation of facial expressions was malleable: 48% of children who selected the fear, anger, sadness, and disgust faces for the "correct" category also selected these same faces for another emotion category; 47% of adults did so for the sadness and disgust faces. The emotion children and adults attribute to facial expressions is influenced by the emotion category for which they are looking. PMID- 22059521 TI - Enhanced attentional capture in trait anxiety. AB - Attentional Control Theory (ACT) proposes that anxiety is specifically associated with more attentional distraction by salient stimuli. Moreover, there is some suggestion that worry is one mechanism whereby anxiety impairs attentional control. However, direct evidence for these hypotheses is lacking. In the current study we addressed limitations of previous work by examining the relationships between trait anxiety and worry and attentional distraction by a salient, task irrelevant color singleton in a visual search task. Results revealed that trait anxiety, but not worry, was related to increased attentional distraction (i.e., capture) by the color singleton. The current results suggest that anxiety is associated with a general enhancement of bottom-up processes involved in motivational significance detection. (PsycINFO Database Record (c) 2012 APA, all rights reserved). PMID- 22059522 TI - Predicting arsenic relative bioavailability in contaminated soils using meta analysis and relative bioavailability-bioaccessibility regression models. AB - A number of in vitro assays are available for the determination of arsenic (As) bioaccessibility and prediction of As relative bioavailability (RBA) to quantify exposure for site-specific risk assessment. These data are usually considered in isolation; however, meta analysis may provide predictive capabilities for source specific As bioaccessibility and RBA. The objectives of this study were to predict As RBA using previously published in vivo/in vitro correlations and to assess the influence of As sources on As RBA independent of geographical location. Data representing 351 soils (classified based on As source) and 514 independent bioaccessibility values were retrieved from the literature for comparison. Arsenic RBA was predicted using published in vivo/in vitro regression models, and 90th and 95th percentiles were determined for each As source classification and in vitro methodology. Differences in predicted mean As RBA were observed among soils contaminated from different As sources and within source materials when various in vitro methodologies were utilized. However, when in vitro data were standardized by transforming SBRC intestinal, IVG, and PBET data to SBRC gastric phase values (through linear regression models), predicted As RBA values for As sources followed the order CCA posts >= herbicide/pesticide > mining/smelting > gossan soils with 95th percentiles for predicted As RBA of 78.0, 78.4, 67.0, and 23.7%, respectively. PMID- 22059523 TI - Root cause analyses performed in a children's hospital: events, action plan strength, and implementation rates. AB - This study describes the types of events leading to the performance of root cause analyses (RCA) and the implementation rate and quality of the action plans developed for RCAs performed at a free standing children's hospital. Twenty serious adverse events resulting in RCAs took place between January 2007 and June 2009. A wide variety of events triggered RCAs however, 30% involved medication errors. Seventy-eight action plans were developed with an average of 3.9 +/- 1.3 per RCA. Action plans were classified as weaker 46% of the time, intermediate 44% of the time, and stronger 10% of the time. Intermediate or stronger action plans were developed to address 90% of the events. Ninety-five percent of the action plans were implemented. This study demonstrates that RCA can be effectively utilized to consistently generate moderate and high impact action plans to address a diverse array of adverse events within a children's hospital. Near complete implementation of action plans can be achieved. PMID- 22059524 TI - Use of a Monte Carlo analysis within a physiologically based pharmacokinetic model to predict doxycycline residue withdrawal time in edible tissues in swine. AB - The pharmacokinetics of doxycycline were studied following a single intravenous (I.V.) and intramuscular (I.M.) injection of 10 mg/kg into eight healthy pigs. The steady-state tissue/plasma partition coefficients were obtained via a 3-h constant rate infusion (CRI) in four pigs. Based on the results of in vivo studies and the parameters derived from published work, a physiologically based pharmacokinetic (PBPK) model was developed to predict the drug concentration in edible tissues. The predicted values were then compared with those derived from a previous study. To account for individual differences in the processes of drug metabolism and/or diffusion, a Monte Carlo (MC) run of 1000 simulations was incorporated into the PBPK model to predict the doxycycline residue withdrawal times in edible tissues in swine. The withdrawal periods were compared with those derived from linear regression analysis. The PBPK model presented here provided accurate predictions of the observed concentrations in all tissues except for the injection site. The withdrawal times in all edible tissues derived from the MC analysis were longer than those from linear regression analysis. Based on the residues in the injection site and muscle tissue, the MC analysis predicted a withdrawal time of 33 days. Here, we illustrate that MC analysis can be incorporated into the PBPK model to accurately predict doxycycline residue withdrawal time in edible tissues in swine. PMID- 22059525 TI - Usefulness of a semi-quantitative procalcitonin test and the A-DROP Japanese prognostic scale for predicting mortality among adults hospitalized with community-acquired pneumonia. AB - BACKGROUND AND OBJECTIVE: The solid-phase immunoassay, semi-quantitative procalcitonin (PCT) test (B R A H M S PCT-Q) can be used to rapidly categorize PCT levels into four grades. However, the usefulness of this kit for determining the prognosis of adult patients with community-acquired pneumonia (CAP) is unclear. METHODS: A prospective study was conducted in two Japanese hospitals to evaluate the usefulness of this PCT test in determining the prognosis of adult patients with CAP. The accuracy of the age, dehydration, respiratory failure, orientation disturbance, pressure (A-DROP) scale proposed by the Japanese Respiratory Society for prediction of mortality due to CAP was also investigated. Hospitalized CAP patients (n = 226) were enrolled in the study. Comprehensive examinations were performed to determine PCT and CRP concentrations, disease severity based on the A-DROP, pneumonia severity index (PSI) and confusion, urea, respiratory rate, blood pressure, age >=65 (CURB-65) scales and the causative pathogens. The usefulness of the biomarkers and prognostic scales for predicting each outcome were then examined. RESULTS: Twenty of the 170 eligible patients died. PCT levels were strongly positively correlated with PSI (rho = 0.56, P < 0.0001), A-DROP (rho = 0.61, P < 0.0001) and CURB-65 scores (rho = 0.58, P < 0.0001). The areas under the receiver operating characteristic curves (95% CI) for prediction of survival, for CRP, PCT, A-DROP, CURB-65, and PSI were 0.54 (0.42-0.67), 0.80 (0.70-0.90), 0.88 (0.82-0.94), 0.88 (0.82-0.94), and 0.89 (0.85 0.94), respectively. The 30-day mortality among patients who were PCT-positive (>=0.5 ng/mL) was significantly higher than that among PCT-negative patients (log rank test, P < 0.001). CONCLUSIONS: The semi-quantitative PCT test and the A-DROP scale were found to be useful for predicting mortality in adult patients with CAP. PMID- 22059526 TI - Effect of surgical repair on testosterone production in infertile men with varicocele: a meta-analysis. AB - OBJECTIVES: To determine the effect of surgical varicocele repair in improving testicular Leydig cell function as shown by increased testosterone production. METHODS: Eligible studies were searched in Medline and the Pubmed database, and cross-referenced as of 31 May 2011 using the terms "varicocele,""testosterone" and "surgery." The database search, quality assessment and data extraction were independently carried out by two reviewers. Only studies including patients with testosterone evaluation before and after surgery were considered for the analysis. A systematic review and meta-analysis was carried out for continues variables using random effect models. RESULTS: Out of 125 studies, a total of nine were selected, including 814 patients. The combined analysis showed that mean serum testosterone levels after surgical treatment increased by 97.48 ng/dL (95% confidence interval 43.73-151.22, P=0.0004) compared with preoperative levels. CONCLUSIONS: Surgical treatment of varicocele significantly increases testosterone production and improves testicular Leydig cell function. PMID- 22059527 TI - Empirical likelihood for cumulative hazard ratio estimation with covariate adjustment. AB - In medical studies, it is often of scientific interest to evaluate the treatment effect via the ratio of cumulative hazards, especially when those hazards may be nonproportional. To deal with nonproportionality in the Cox regression model, investigators usually assume that the treatment effect has some functional form. However, to do so may create a model misspecification problem because it is generally difficult to justify the specific parametric form chosen for the treatment effect. In this article, we employ empirical likelihood (EL) to develop a nonparametric estimator of the cumulative hazard ratio with covariate adjustment under two nonproportional hazard models, one that is stratified, as well as a less restrictive framework involving group-specific treatment adjustment. The asymptotic properties of the EL ratio statistic are derived in each situation and the finite-sample properties of EL-based estimators are assessed via simulation studies. Simultaneous confidence bands for all values of the adjusted cumulative hazard ratio in a fixed interval of interest are also developed. The proposed methods are illustrated using two different datasets concerning the survival experience of patients with non-Hodgkin's lymphoma or ovarian cancer. PMID- 22059528 TI - Evidence-informed decision-making by professionals working in addiction agencies serving women: a descriptive qualitative study. AB - BACKGROUND: Effective approaches to the prevention and treatment of substance abuse among mothers have been developed but not widely implemented. Implementation studies suggest that the adoption of evidence-based practices in the field of addictions remains low. There is a need, therefore, to better understand decision making processes in addiction agencies in order to develop more effective approaches to promote the translation of knowledge gained from addictions research into clinical practice. METHODS: A descriptive qualitative study was conducted to explore: 1) the types and sources of evidence used to inform practice-related decisions within Canadian addiction agencies serving women; 2) how decision makers at different levels report using research evidence; and 3) factors that influence evidence-informed decision making. A purposeful sample of 26 decision-makers providing addiction treatment services to women completed in-depth qualitative interviews. Interview data were coded and analyzed using directed and summative content analysis strategies as well as constant comparison techniques. RESULTS: Across all groups, individuals reported locating and using multiple types of evidence to inform decisions. Some decision-makers rely on their experiential knowledge of addiction and recovery in decision making. Research evidence is often used directly in decision-making at program management and senior administrative levels. Information for decision-making is accessed from a range of sources, including web-based resources and experts in the field. Individual and organizational facilitators and barriers to using research evidence in decision making were identified. CONCLUSIONS: There is support at administrative levels for integrating EIDM in addiction agencies. Knowledge transfer and exchange strategies should be focussed towards program managers and administrators and include capacity building for locating, appraising and using research evidence, knowledge brokering, and for partnering with universities. Resources are required to maintain web-based databases of searchable evidence to facilitate access to research evidence. A need exists to address the perception that there is a paucity of research evidence available to inform program decisions. Finally, there is a need to consider how experiential knowledge influences decision-making and what guidance research evidence has to offer regarding the implementation of different treatment approaches within the field of addictions. PMID- 22059529 TI - Analysis of two marine metagenomes reveals the diversity of plasmids in oceanic environments. AB - Plasmid diversity is still poorly understood in pelagic marine environments. Metagenomic approaches have the potential to reveal the genetic diversity of microbes actually present in an environment and the contribution of mobile genetic elements such as plasmids. By searching metagenomic datasets from flow cytometry-sorted coastal California seawater samples dominated by cyanobacteria (SynMeta) and from the Global Ocean Survey (GOS) putative marine plasmid sequences were identified as well as their possible hosts in the same samples. Based on conserved plasmid replication protein sequences predicted from the SynMeta metagenomes, PCR primers were designed for amplification of one plasmid family and used to confirm that metagenomic contigs of this family were derived from plasmids. These results suggest that the majority of plasmids in SynMeta metagenomes were small and cryptic, encoding mostly their own replication proteins. In contrast, probable plasmid sequences identified in the GOS dataset showed more complexity, consistent with a much more diverse microbial population, and included genes involved in plasmid transfer, mobilization, stability and partitioning. Phylogenetic trees were constructed based on common replication protein functional domains and, even within one replication domain family, substantial diversity was found within and between different samples. However, some replication protein domain families appear to be rare in the marine environment. PMID- 22059530 TI - In vitro evaluation of flavonoids from Eriodictyon californicum for antagonist activity against the bitterness receptor hTAS2R31. AB - The leaves of the native North American plant, Eriodictyon californicum, were once used to mask the bitter taste of pharmaceuticals, an application currently of importance. Ten flavonoids (1-10) were isolated from the leaves of E. californicum, of which the structure and absolute configuration of 6 methoxyhesperetin (8) were assigned for the first time. In addition, the absolute configurations at C-2 were established for 4'-isobutyrylhomoeriodictyol (3) and 6 methoxyhomoeriodictyol (7). Using a cell-based assay, it was determined that the 7-methoxylated flavanones, sakuranetin (2) and 6-methoxysakuranetin (9), and the flavone, jaceosidin (10), are antagonists of hTAS2R31. PMID- 22059531 TI - A study of neurocognition in bulimia nervosa and eating disorder not otherwise specified-bulimia type. AB - Neurocognition in bulimia nervosa (BN) is under-researched. This study investigated aspects of attention (d2-Letter Cancellation Task), inhibitory control (Stroop and go/no-go task), and decision making (Game of Dice Task) in 40 people with BN, 30 with eating disorder not otherwise specified-BN type (EDNOS BN), and 65 healthy controls (HCs). The National Adult Reading Test (NART) and Depression Anxiety Stress Scale (DASS-21) were also administered. Analyses of covariance (covariates: age, NART, and DASS-21) showed that people with BN and EDNOS-BN performed as well as HCs on all tasks. Attention task performance was poorer in the EDNOS-BN than in the BN group. PMID- 22059532 TI - Statins after recent stroke reduces recurrence and improves survival in an aging Mediterranean population without known coronary heart disease. AB - WHAT IS KNOWN AND OBJECTIVE: The effect of a statin-based medical intervention on prevention of fatal and non-fatal stroke recurrence and the incidence of all causes mortality have been explored previously in aging populations within the scope of clinical trials research. However, such evidence needs to be explored under conditions of routine clinical practice. The objective of this study was to determine whether statin therapy in patients with a first stroke episode reduces the incidence of 6-year recurrent fatal or non-fatal stroke and all-cause mortality in an aging Mediterranean population without known coronary heart disease followed in routine medical practice. METHODS: A retrospective study was carried out using records on death, hospitalizations owing to stroke and history of statin therapy included in the Badalona Serveis Assistencials (BSA) database. The cohort studied consisted of consecutive patients covered by the BSA health provider plan with a first-ever acute stroke episode during January 2003 until December 2008, for whom there was available information covering the 6-year follow-up period. Recurrence rate (RR) and incidence rate (IR) of fatal/non-fatal stroke and all-causes mortality were computed. Association with statin therapy was assessed by means of calculation of relative risk (RR) and hazard ratio (HR) using multivariate logistic regression and Cox proportional hazards models controlling for confounding covariates. RESULTS AND DISCUSSION: The cohort comprised a series of 601 consecutive patients [57% men, 75.9 (12.4) years old (88% >60 years)]. Of these, 32% received statins, which were associated with lower fatal/non-fatal recurrent stroke RR; 7% vs. 18% [adjusted RR=0.32 (CI: 0.16 0.61), P=0.001] and lower IR; 16.78 vs. 45.22 events/year-1000 subjects [adjusted HR=0.35 (0.19-0.64), P=0.001]. Similarly, observed all-causes mortality was lower in the cohort receiving statins; 11% vs. 16% [adjusted RR=0.29 (CI: 0.08-1.12), P=0.072], and also mortality rate; 26.09 vs. 36.25 deaths/year-1000 subjects [adjusted HR=0.23 (0.08-0.67), P=0.007]. WHAT IS NEW AND CONCLUSIONS: Statin therapy in patients with first-ever acute stroke lowers the risk of 6-year stroke recurrence and improves survival in an aging Mediterranean cohort. These results add additional evidence in routine clinical practice to the observed effects of statins in clinical trials. PMID- 22059533 TI - Induction of methionine-sulfoxide reductases protects neurons from amyloid beta protein insults in vitro and in vivo. AB - Self-assembly of amyloid beta-protein (Abeta) into toxic oligomers and fibrillar polymers is believed to cause Alzheimer's disease (AD). In the AD brain, a high percentage of Abeta contains Met-sulfoxide at position 35, though the role this modification plays in AD is not clear. Oxidation of Met(35) to sulfoxide has been reported to decrease the extent of Abeta assembly and neurotoxicity, whereas surprisingly, oxidation of Met(35) to sulfone yields a toxicity similar to that of unoxidized Abeta. We hypothesized that the lower toxicity of Abeta-sulfoxide might result not only from structural alteration of the C-terminal region but also from activation of methionine-sulfoxide reductase (Msr), an important component of the cellular antioxidant system. Supporting this hypothesis, we found that the low toxicity of Abeta-sulfoxide correlated with induction of Msr activity. In agreement with these observations, in MsrA(-/-) mice the difference in toxicity between native Abeta and Abeta-sulfoxide was essentially eliminated. Subsequently, we found that treatment with N-acetyl-Met-sulfoxide could induce Msr activity and protect neuronal cells from Abeta toxicity. In addition, we measured Msr activity in a double-transgenic mouse model of AD and found that it was increased significantly relative to that of nontransgenic mice. Immunization with a novel Met-sulfoxide-rich antigen for 6 months led to antibody production, decreased Msr activity, and lowered hippocampal plaque burden. The data suggest an important neuroprotective role for the Msr system in the AD brain, which may lead to development of new therapeutic approaches for AD. PMID- 22059534 TI - Automated assessment of the neutrophil and platelet activation status in patients with essential thrombocythemia. AB - Neutrophil and platelet activation are consistently found in essential thrombocythemia (ET), but the techniques employed to demonstrate such abnormalities are complex. To ascertain whether the ADVIA 120 analyzer can be employed to assess neutrophil and platelet activation status in ET, 55 such patients and the same number of matched healthy individuals were studied and the results correlated with neutrophil CD11b and platelet P-selectin expressions measured by flow cytometry. Compared with controls, ET patients had significantly higher values of neutrophil myeloperoxidase index (MPXI), mean platelet volume (MPV), platelet distribution width (PDW), and platelet component distribution width, and significantly lower values of neutrophil lobularity index and mean platelet component (MPC). Patients with the JAK2 mutation had significantly lower values of MPC and higher values of MPV and PDW than those with wild-type allele. A positive correlation was observed between MPXI and neutrophil CD11b expression and a negative correlation between MPC and platelet P-selectin expression. The intensity of the agreement between the variables obtained by the two methods was moderate. These results support the possible value of MPC as surrogate parameter of platelet activation in ET. PMID- 22059535 TI - A review on the use of hyaluronic acid in tympanic membrane wound healing. AB - INTRODUCTION: Tympanic membrane perforation represents a significant morbidity, especially if it occurs during a child's speech and language development. Recently, there has been an increased interest in hyaluronic-acid-related research and products as a potential therapeutic option for tympanic membrane perforation repair. AREAS COVERED: This review describes the physical and chemical properties of hyaluronic acid and examines the role of hyaluronic acid in wound healing, in particular on the tympanic membrane. It also reviews the safety and efficacy of hyaluronic acid and its derivatives in animal studies as well as in clinical trials. Finally, it considers the potential future clinical applications in tympanic membrane perforation repair. EXPERT OPINION: Hyaluronic acid has been found to accelerate tympanic membrane perforation closure, shorten the period of healing, produce a better quality neo-membrane and improve hearing. More importantly, hyaluronic acid is biodegradable, safe and biocompatible in the ear. Recently, there has been a trend towards the use of modified hyaluronic acid. However, there is a lack of higher-level evidence to support the use of hyaluronic acid in tympanic membrane perforations in the clinical setting. More large-scale randomised control trials are warranted before these bio-devices will be used routinely. PMID- 22059536 TI - Reversible switching of a cobalt complex by thermal, pressure, and electrochemical stimuli: abrupt, complete, hysteretic spin crossover. AB - Triply switchable [Co(II)(dpzca)(2)] shows an abrupt, reversible, and hysteretic spin crossover (T(1/2)? = 168 K, T(1/2)? = 179 K, and DeltaT(1/2) = 11 K) between the high-spin (HS) and low-spin (LS) states of cobalt(II), both of which have been structurally characterized. The spin transition is also reversibly triggered by pressure changes. Moreover, in a third reversible switching mechanism for this complex, the magnetic properties can be switched between HS cobalt(II) and LS cobalt(III) by redox. PMID- 22059537 TI - Inhibition of Yersinia enterocolitica by Lactobacillus sake strains of meat origin. AB - The growth of Yersinia enterocolitica at 4, 8, 15 and 24 degrees C, in mixed cultures with Lactobacillus sake strains previously isolated from Spanish dry fermented sausages was investigated. Growth of Y. enterocolitica was affected by L. sake strains at all temperatures studied. The inhibition was higher as the incubation temperature increased. L. sake 148, a bacteriocinogenic strain, was less inhibitory to Y. enterocolitica growth than L. sake 23, a stronger lactic acid producer strain. The low pH and the lactic acid produced by the lactobacilli seem to be major factors contributing to the inhibition of Y. enterocolitica strains. PMID- 22059538 TI - Relationships between post-mortem pH changes and some traits of sensory quality in veal. AB - The aim of this study was to evaluate the relationships between the rate and extent of post-mortem pH changes and the colour, the cooking loss and the eating quality of veal. The experiment used 12 calves aged 18 weeks. Variations in ultimate pH were induced by adrenalin administration (0.1-0.4 mg/kg liveweight) to six of the animals. Measurements were made on the Longissimus thoracis muscle. pH and osmotic pressure were measured at 0.5 h, 4 h and 29 h after slaughter. Pigment content, drip loss and cooking loss were measured at 29 h after slaughter, and colour was measured at 2 days and 9 days after slaughter. Cooking loss, tenderness, juiciness and flavour of roasts were assessed at 9 days after slaughter. Correlations between colour traits and pH values were higher with ultimate pH than with pH at 0.5 h or 4 h after slaughter. Lightness, redness and reflectance decreased when the ultimate pH increased. Drip loss was correlated with the rate of pH fall (r = -0.80, P < 0.01 with pH at 4 h), while cooking loss was correlated with ultimate pH (r = -0.94, P < 0.01). Ultimate pH and the sensory quality traits were linearity and positively correlated (r = 0.83) for tenderness, 0.81 for juiciness and 0.71 for flavour, respectively). PMID- 22059539 TI - Absence of volatile N-nitrosamines in cooked nitrite-free cured muscle foods. AB - Nitrite-free cured pork systems were prepared using the preformed cooked cured meat pigment (CCMP) and sodium ascorbate. Absence of volatile N-nitrosamines in cooked nitrite-free systems was confirmed using a gas chromatography-thermal energy analyzer (GC-TEA) methodology. Similar results were obtained when cod, cod surimi or mixtures containing pork with 15 or 50% cod or cod surimi were used. However, counterpart samples cured with sodium nitrite (156 ppm) and sodium ascorbate (550 ppm) produced N-nitrosodimethylamine at 1.0 ppb levels or less. Results demonstrate that nitrite-free curing of meat and meat/fish systems containing the preformed CCMP is successful in yielding products devoid of volatile N-nitrosamines. PMID- 22059540 TI - Polymerase chain reaction assay for detection of sheep and goat meats. AB - Polymerase Chain Reaction (PCR) was applied to a qualitative differentiation between sheep, goat and bovine meats. Oligonucleotide primers were designed for the amplification of sheep satellite I DNA sequence. The PCR amplified 374 bp fragments from sheep and goat DNA, but no fragment from bovine, water buffalo, sika deer, pig, horse, rabbit and chicken DNA. Sheep DNA (10 pg) was detected by 4% agarose gel electrophoresis following PCR amplification. Althoug cooking of the sample meats reduced the PCR products, sheep DNA was detected in the meat heated at 120 degrees C. In order to differentiate between sheep and goat meats, nucleotide sequences of the PCR products were determined directly by cycle sequencing. The sequence of PCR products showed 92% of homology between sheep and goat. They were differentiated by ApaI digestion of the PCR products because sheep had one ApaI site and goat had no site in the PCR products. PMID- 22059541 TI - Studies on processing and refrigerated storage of 'Rista'. AB - Effects of mutton fat levels, hot-boned versus cold-boned meat and manual versus machine mincing were studied on the quality of 'Rista'-a popular emulsion type ground meat product of Kashmir (India). Incorporation of lamb fat at 20% level was found optimum for processing Rista. Both pre-rigor and chilled (post-rigor) meat were utilised for product manufacture. Addition of 0.5% sodium tripolyphosphate improved product binding, texture and yield. All these effects were more pronounced in machine minced Rista samples processed from cold-boned lamb meat, as compared with hot-processed and hand minced product. Cooked Rista was stored in low density polyethylene bags (0.25 MUm thickness) at 4 +/- 1 degrees C in satifactory condition for 4 days. PMID- 22059542 TI - Effects of high pressure treatment on the flavour-related components in meat. AB - This paper describes the effects of high-pressure treatment on the water-soluble components of meat responsible for the flavor of meat. The amounts of peptides and amino acids as estimated by phenol reagent positive materials (PPM) apparently increased with increasing pressure applied to the muscle up to 300 MPa, but the differences between each treatment were not statistically significant. When the muscles were stored at 2 degrees C for 7 days after the pressurization, increases in the amount of PPM were observed both in untreated and pressurized muscles. Apparently the contents of serine, glutamic acid, glutamine, glycine and alanine gradually increased in the extracts from pressurized muscle as the pressure increased up to 200 MPa, and some of them, especially glutamine and alanine, tended to decrease in the muscle pressurized at 300 MPa. When the muscles were stored for 7 days after the pressurization, apparent increases of the contents of aspartic acid, serine, proline, alanine and lysine were observed in the extracts both from untreated and pressurized muscles. However, significant differences were not observed in the contents of each amino acid between each treatment. The content of inosinic acid, which is considered to contribute to the 'umani' taste of the meat, was not reduced by the pressurization. High performance liquid chromatograph (HPLC) of soluble peptides revealed no significant changes in any fraction from the pressurized muscles up to 200 MPa and a significant decrease of the peptide fraction (approx. molecular weight 500) from the muscle pressurized at 300 and 400 MPa. When the muscles were stored after pressurization, significant increases in the peptide fraction of molecular weight 300 and the amino acid fraction, and a decrease of the peptide fraction of molecular weight 3000 were observed in the extracts both from the untreated and pressurized muscles. From the results, it is suggested that high pressure treatment on the post mortem muscle causes almost the same changes in the components responsible for the flavor of meat as those observed in conditioned muscle. PMID- 22059543 TI - The use of a high pressure waterjet combined with electroimmobilization for the stunning of slaughter pigs: Some aspects of meat quality. AB - It is considered that waterjet stunning may be a humane stunning method to apply in slaughter facilities. An experiment was conducted in a slaughterhouse to examine the effects of waterjet stunning combined with electroimmobilization during exsanguination on the occurrence of haemorrhages in the muscles and on meat quality. Slaughter pigs (n = 31) were stunned by waterjet (3900 bar) in a V type restrainer and immobilized electrically (40 V) during exsanguination. Control animals (n = 39) were stunned automatically and electrically (600 V) using the same restraint device. At 45 min post mortem the pH in the semimembranosus (SM) and longissimus dorsi (LD) muscles was significantly lower (p < 0.01), while rigor mortis and temperature in the SM and LD were significantly higher (p < 0.05 and p < 0.01, respectively) in the carcasses of pigs stunned with the waterjet as compared to control pigs. At 18 h post mortem the ultimate pH of the LD was lower (p < 0.05), while scatter (fibre optic probe) and filter paper test values of the LD were higher (p < 0.01) in carcasses of pigs stunned with the waterjet. Fewer haemorrhages were observed in the shoulders of pigs stunned with the waterjet. The results of this experiment suggest that waterjet stunning, when combined with electroimmobilization, may be a suitable method to stun pigs in a slaughterhouse. However, further studies are required to improve the meat quality. PMID- 22059544 TI - Modelling post-mortem tenderisation-V: Inactivation of calpains. AB - The calpain-activity model, which allows computation of the in-situ activities of calpains, was used to predict tenderisation. Tenderisation results from the net proteolysis which is governed by the relative activities and the intramolecular inactivation of calpains. The activity increases non-interactively with increase in pH and increase in temperature. The rate of inactivation depends interactively upon pH and temperature. At high temperature, inactivation is high and almost independent of pH. The rate of inactivation decreases with decrease in temperature, but below about 10 degrees C it increases at low pH. Rapid rigor development produces rapid activation and tenderisation but it may be short lived, particularly in slowly-chilled meat, producing tough meat. Rapid cooling causes rapid inactivation of calpains and can give rise to very tough meat. Therefore, the calpain-activity model predicts the toughness often observed in PSE meats and rapidly-chilled meats without evoking structural changes dependent upon water-holding capacity or the degree of overlap of actin and myosin. Furthermore, the model demonstrates the known interactions of ageing with these conditions, interactions which cannot be explained by those structural changes alone. Variations in post-mortem activity of calpains therefore provide a single concept accounting for the variations in texture arising from variations in animal production, chilling and ageing and their interactions. PMID- 22059545 TI - Objective assessment of pork quality. AB - Several objective methods for estimating pork quality were studied: internal light scattering (FOP), electrical conductivity (EC), pH, colour, water holding capacity (WHC), soluble proteins (SP), pigment content, intramuscular fat (i.m. fat), and moisture. The measurements were made on the Semimembranosus and Longissimus thoracis at 45 min and 24 h post mortem in some cases and on the Semimembranosus in others. Most of the measurements are significantly different between normal, PSE and DFD quality categories. There is a good correlation between pH values in both muscles: pH(45)SM-pH(45)LT (r=0.74) and pH(24)SM pH(24)LT (r=0.71). At 45 min the correlation of EC with FOP and pH was r=0.56 and r=0.48 respectively. Lower correlations were found in other parameters. The results from principal component analysis (PCA) showed that the three first components explained 60.3% of the total variation and the most important variables for the first PC were pH(45) and EC(45). PMID- 22059546 TI - Objective meat quality measurements of ham: A practical classification method on the slaughterline. AB - Meat quality is one of the principal problems in Spanish dry cured ham productuon. At the experimental level, there are well developed objective instrumental measurements which can be made on the slaughterline and then, by applying the correct statistical treatment, these measurements can be used to classify hams with an acceptable degree of accuracy. These treatments, however, are not easy to apply in the industry. In this work, 312 pork carcasses were tested at three industrial abbatoirs. Ham meat quality was determined by internal light scattering (FOP), electrical conductivity (EC) and pH measurements in Semimembranosus (SM) muscle at 45 min and 24 h post mortem. The results obtained were: 21 (6.7%) DFD; 168 (53.9%) slightly DFD; 104 (33.3%) normal; 11 (3.5%) slightly PSE; and 8 (2.6%) PSE. A simplified method has been developed for classifying hams into quality categories, by deriving a theoretical quality value (Q) based on a simple statistical treatment of values for FOP, EC and pH. The multiple linear regression coefficient of Q was R(2) = 0.85 (P<0.001) with respect to the experimental variables. PMID- 22059547 TI - The effects of antifreeze proteins on chilled and frozen meat. AB - The effects of cryoprotectant proteins, trivially termed 'antifreeze proteins', from the Antarctic Cod and the Winter Flounder were assessed in meat during chilling and freezing. In light-microscopy studies, bovine muscle (Sternomandibularis) samples were soaked in phosphate buffered saline with and without 0.1 mg/ml antifreeze protein. Samples were then held frozen (-20 degrees C) or chilled (2 degrees C) for 3 days. Samples were freeze-substituted, embedded in resin and sectioned. With antifreeze protein present, transverse sections of frozen samples had many small intracellular spaces, probably representing ice crystals. Frozen controls had much larger intracellular single spaces. Antifreeze protein had no effect on chilled samples. Similarly treated samples were examined by scanning electron microscopy using a cryostage attachment. Chilled ovine muscle samples (Peroneus longus) were soaked for various periods (0-7 days) in 0.9% saline containing various concentrations of antifreeze proteins (0-1 mg/ml). Samples were then held frozen (-20 degrees C) or chilled (2 degrees C) for 5 or 7 days. With frozen samples, antifreeze proteins reduced the size of ice crystals, compared to the control. This effect depended upon the concentration used and the period of soaking before the samples were frozen, but was independent of source. Antifreeze proteins had no effect on chilled samples. PMID- 22059548 TI - Effect of gamma radiation on total tocopherols in fresh chicken breast muscle. AB - Chicken breasts were irradiated in air with a (137)Cs source at 0.0., 1.0, 3.0, 5.6 and 10.0 kGy at 0-2 degrees C. The fresh muscle tissue was saponified and the total tocopherols were isolated and quantitated using normal phase high performance liquid chromatography with a fluorescence detector. Gamma irradiation of the chicken resulted in a decrease in alpha tocopherol with increasing dose. At 3 kGy and 2 degrees C, the radiation level approved by the FDA to process poultry, there was a 6% reduction in the alpha tocopherol level. No significant changes were observed for gamma tocopherol. PMID- 22059549 TI - Time-related changes in nitrogen fractions and free amino acids of lean tissue of frech dry-cured ham. AB - The 80 hams of 40 pig carcasses from one slaughter batch were taken on the day after slaughter. The 40 left hams were dry-cured. Groups of 10 hams were taken for analysis at 74 days (end of rest), 81 days (end of heating), 179 days (mid seasoning) and 273 days (end of seasoning) after the beginning of processing. A slice of about 150 g was taken in the middle of the Biceps femoris and used for analysis of nitrogen fractions and free amino acids by HPLC. Levels of insoluble nitrogen compounds did not vary significantly, while levels of soluble protein nitrogen decreased strongly from 26 to 16% of total nitrogen, with the fastest decrease observed between days 179 and 273. Levels of non-protein nitrogen increased regularly during the processing from 12 to 23% of total nitrogen. Nitrogen of free amino acids ranged from 3.6% in fresh muscle to 16.6% of total nitrogen at day 179, then decreased to 4.4% of the total nitrogen at the end of the processing. The HPLC method allowed the identification of 29 compounds, among which 27 were amino acids and 2 were dipeptides. The average levels of free amino acids of non-protein origin tended to decrease before day 74, then to increase until day 179 and to decrease again. The levels of compounds of protein origin increased or tended to increase from the beginning until day 179, then decreased. PMID- 22059552 TI - Stereoselective synthesis of uridine-derived nucleosyl amino acids. AB - Novel hybrid structures of 5'-deoxyuridine and glycine were conceived and synthesized. Such nucleosyl amino acids (NAAs) represent simplified analogues of the core structure of muraymycin nucleoside antibiotics, making them useful synthetic building blocks for structure-activity relationship (SAR) studies. The key step of the developed synthetic route was the efficient and highly diastereoselective asymmetric hydrogenation of didehydro amino acid precursors toward protected NAAs. It was anticipated that the synthesis of unprotected muraymycin derivatives via this route would require a suitable intermediate protecting group at the N-3 of the uracil base. After initial attempts using PMB- and BOM-N-3 protection, both of which resulted in problematic deprotection steps, an N-3 protecting group-free route was envisaged. In spite of the pronounced acidity of the uracil-3-NH, this route worked equally efficient and with identical stereoselectivities as the initial strategies involving N-3 protection. The obtained NAA building blocks were employed for the synthesis of truncated 5' deoxymuraymycin analogues. PMID- 22059554 TI - A model of habitability within the Milky Way galaxy. AB - We present a model of the galactic habitable zone (GHZ), described in terms of the spatial and temporal dimensions of the Galaxy that may favor the development of complex life. The Milky Way galaxy was modeled using a computational approach by populating stars and their planetary systems on an individual basis by employing Monte Carlo methods. We began with well-established properties of the disk of the Milky Way, such as the stellar number density distribution, the initial mass function, the star formation history, and the metallicity gradient as a function of radial position and time. We varied some of these properties and created four models to test the sensitivity of our assumptions. To assess habitability on the galactic scale, we modeled supernova rates, planet formation, and the time required for complex life to evolve. Our study has improved on other literature on the GHZ by populating stars on an individual basis and modeling Type II supernova (SNII) and Type Ia supernova (SNIa) sterilizations by selecting their progenitors from within this preexisting stellar population. Furthermore, we considered habitability on tidally locked and non-tidally locked planets separately and studied habitability as a function of height above and below the galactic midplane. In the model that most accurately reproduces the properties of the Galaxy, the results indicate that an individual SNIa is ~5.6* more lethal than an individual SNII on average. In addition, we predict that ~1.2% of all stars host a planet that may have been capable of supporting complex life at some point in the history of the Galaxy. Of those stars with a habitable planet, ~75% of planets are predicted to be in a tidally locked configuration with their host star. The majority of these planets that may support complex life are found toward the inner Galaxy, distributed within, and significantly above and below, the galactic midplane. PMID- 22059553 TI - VEGF signaling mediates bladder neuroplasticity and inflammation in response to BCG. AB - BACKGROUND: This work tests the hypothesis that increased levels of vascular endothelial growth factor (VEGF) observed during bladder inflammation modulates nerve plasticity. METHODS: Chronic inflammation was induced by intravesical instillations of Bacillus Calmette-Guerin (BCG) into the urinary bladder and the density of nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) or pan-neuronal marker PGP9.5 was used to quantify alterations in peripheral nerve plasticity. Some mice were treated with B20, a VEGF neutralizing antibody to reduce the participation of VEGF. Additional mice were treated systemically with antibodies engineered to specifically block the binding of VEGF to NRP1 (anti-NRP1B) and NRP2 (NRP2B), or the binding of semaphorins to NRP1 (anti-NRP1 A) to diminish activity of axon guidance molecules such as neuropilins (NRPs) and semaphorins (SEMAs). To confirm that VEGF is capable of inducing inflammation and neuronal plasticity, another group of mice was instilled with recombinant VEGF165 or VEGF121 into the urinary bladder. RESULTS: The major finding of this work was that chronic BCG instillation resulted in inflammation and an overwhelming increase in both PGP9.5 and TRPV1 immunoreactivity, primarily in the sub-urothelium of the urinary bladder. Treatment of mice with anti-VEGF neutralizing antibody (B20) abolished the effect of BCG on inflammation and nerve density.NRP1A and NRP1B antibodies, known to reduce BCG-induced inflammation, failed to block BCG-induced increase in nerve fibers. However, the NRP2B antibody dramatically potentiated the effects of BCG in increasing PGP9.5-, TRPV1-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactivity (IR). Finally, instillation of VEGF121 or VEGF165 into the mouse bladder recapitulated the effects of BCG and resulted in a significant inflammation and increase in nerve density. CONCLUSIONS: For the first time, evidence is being presented supporting that chronic BCG instillation into the mouse bladder promotes a significant increase in peripheral nerve density that was mimicked by VEGF instillation. Effects of BCG were abolished by pre-treatment with neutralizing VEGF antibody. The present results implicate the VEGF pathway as a key modulator of inflammation and nerve plasticity, introduces a new animal model for investigation of VEGF-induced nerve plasticity, and suggests putative mechanisms underlying this phenomenon. PMID- 22059555 TI - Human leucocyte antigen typing: techniques and technology, a critical appraisal. AB - Methods for the identification of Human Leukocyte Antigens (HLA) have changed significantly since this group of polymorphic proteins were first characterized by serological reagents in the 1960s and 1970s. The invention and development of the Polymerase Chain Reaction (PCR) has been key in the progress of methods for HLA genotyping. As the complexity of HLA polymorphism has unravelled so it has exposed the weaknesses in techniques such as PCR - Restriction Fragment Length Polymorphism (RFLP) and Reference Strand Mediated Conformation Analysis (RSCA), which are no longer in use today. Methods which have been considered routine laboratory tools in recent years, such as Sequence-Specific Primer - PCR and Sequencing Based Typing (SBT) are now also threatened with extinction, not only because of the depth of HLA variation but also because of the rapid development of Next Generation Sequencing and technologies which will follow this. This review describes the merits and disadvantages of current technologies available to HLA Typing laboratories, future trends and the problems posed by new alleles. PMID- 22059556 TI - Asthma-related SNP in FCER2 is associated with increased expression of IL-4R on human B cells. AB - A SNP (rs2228137) (R62W) in FCER2 has been linked with severe exacerbations in asthmatics. Transfectants expressing the SNP exhibited increased IL-4Ralpha expression after stimulation through CD23 compared with wild-type. Our data suggest that the SNP may favour increased IgE production through increased responsiveness to IL-4 in patients possessing this genotype. PMID- 22059557 TI - Asthma severity, child security, and child internalizing: using story stem techniques to assess the meaning children give to family and disease-specific events. AB - Children with persistent asthma are at increased risk for mental health problems. Although mechanisms of effect are not yet known, it may be that children are less trusting of the family as a source of support and security when they have more severe asthma. This study tested whether asthma severity is related to children's perceptions of insecurity in the family, and whether insecurity is in turn associated with child adjustment. Children (N = 168; mean age = 8 years) completed story stems pertaining to routine family events (e.g., mealtimes) and ambiguous but potentially threatening asthma events such as tightness in the chest. Responses were evaluated for the extent to which appraisals portrayed the family as responding in cohesive, security-provoking ways. Asthma severity was assessed by both objective lung function testing and primary caregiver report. Caregivers reported child symptomatology. Beyond medication adherence, caregiver education, and child age and gender, greater asthma severity predicted more internalizing and externalizing symptoms. Greater asthma severity, assessed using spirometry (but not parent report), was related to less secure child narratives of the family, which in turn related to more child internalizing symptoms. Results suggest that asthma can take a considerable toll on children's feelings of security and mental health. Furthermore, given the difficulty in assessing young children's perceptions, this study helps demonstrate the potential of story stem techniques in assessing children's appraisals of illness threat and management in the family. PMID- 22059558 TI - Critical outcomes: clinical and team performance across acute illness scenarios in emergency departments of critical access hospitals. AB - In their provision of acute care services, emergency department (ED) providers in critical access hospitals (CAHs) are uniquely challenged by limitations in personnel, facility resources, and available expertise. We sought to define the impact of team behaviors among ED staff in CAHs on clinical performance by studying the relationship between team and clinical performance scores across 100 simulated scenarios. Team and clinical performance scores were calculated for each scenario using standardized checklists to quantify goal achievement and aggregated across teams and scenario types. These scores were compared using bivariate analysis and correlated with clinical and team performance outcomes using Pearson's correlation (r coefficient). There was a positive correlation between team and clinical performance across all scenarios; the relationship was statistically significant (p<.05) in 3 scenarios: acute coronary syndrome (r=.69; p=.027); abdominal aortic aneurysm (r=.77; p=.009); and nonaccidental trauma (r=.75; p=.013). The wide correlation between clinical and team performance may be a function of the critical care event itself or the unique characteristics of CAHs that make them more vulnerable when faced with high acuity, complex, and infrequently encountered clinical scenarios. PMID- 22059559 TI - Online detection and quantification of ergot bodies in cereals using near infrared hyperspectral imaging. AB - The occurrence of ergot bodies (sclerotia of Claviceps purpurea) in cereals presents a high toxicity risk for animals and humans due to the alkaloid content. To reduce this risk, the European Commission fixed an ergot concentration limit of 0.1% in all feedstuffs containing unground cereals, and a limit of 0.05% in 'intervention' cereals destined for humans. This study sought to develop a procedure based on near infrared hyperspectral imaging and multivariate image analysis to detect and quantify ergot contamination in cereals. Hyperspectral images were collected using an NIR hyperspectral line scan combined with a conveyor belt. All images consisted of lines of 320 pixels that were acquired at 209 wavelength channels (1100-2400 nm). To test the procedure, several wheat samples with different levels of ergot contamination were prepared. The results showed a correlation higher than 0.99 between the predicted values obtained using chemometric tools such as partial least squares discriminant analysis or support vector machine and the reference values. For a wheat sample with a level of ergot contamination as low as 0.01 %, it was possible to identify groups of pixels detected as ergot to conclude that the sample was contaminated. In addition, no false positives were obtained with non-contaminated samples. The limit of detection was found to be 145 mg/kg and the limit of quantification 341 mg/kg. The reproducibility tests of the measurements performed over several weeks showed that the results were always within the limits allowed. Additional studies were done to optimise the parameters in terms of number of samples analysed per unit of time or conveyor belt speed. It was shown that ergot can be detected using a speed of 1-100 mm/s and that a sample of 250 g can be analysed in 1 min. PMID- 22059560 TI - Beach monitoring criteria: reading the fine print. AB - Beach monitoring programs aim to decrease swimming-related illnesses resulting from exposure to harmful microbes in recreational waters, while providing maximum beach access. Managers are advised by the U.S. EPA to estimate microbiological water quality based on a 5-day geometric mean of fecal indicator bacteria (FIB) concentrations or on a jurisdiction-specific single-sample maximum; however, most opt instead to apply a default single-sample maximum to ease application. We examined whether re-evaluation of the U.S. EPA ambient water quality criteria (AWQC) and the epidemiological studies on which they are based could increase public beach access without affecting presumed health risk. Single-sample maxima were calculated using historic monitoring data for 50 beaches along coastal Lake Michigan on various temporal and spatial groupings to assess flexibility in the application of the AWQC. No calculation on either scale was as low as the default maximum (235 CFU/100 mL) that managers typically use, indicating that current applications may be more conservative than the outlined AWQC. It was notable that beaches subject to point source FIB contamination had lower variation, highlighting the bias in the standards for these beaches. Until new water quality standards are promulgated, more site-specific application of the AWQC may benefit beach managers by allowing swimmers greater access to beaches. This issue will be an important consideration in addressing the forthcoming beach monitoring standards. PMID- 22059561 TI - Geographic variation in the structure of oak hybrid zones provides insights into the dynamics of speciation. AB - Studying geographic variation in the rate of hybridization between closely related species could provide a useful window on the evolution of reproductive isolation. Reinforcement theory predicts greater prezygotic isolation in areas of prolonged contact between recently diverged species than in areas of recent contact, which implies that old contact zones would be dominated by parental phenotypes with few hybrids (bimodal hybrid zones), whereas recent contact zones would be characterized by hybrid swarms (unimodal hybrid zones). Here, we investigate how the hybrid zones of two closely related Chinese oaks, Quercus mongolica and Q. liaotungensis, are structured geographically using both nuclear and chloroplast markers. We found that populations of Q. liaotungensis located around the Changbai Mountains in Northeast China, an inferred glacial refugium, were introgressed by genes from Q. mongolica, suggesting historical contact between the two species in this region. However, these introgressed populations form sharp bimodal hybrid zones with Q. mongolica. In contrast, populations of Q. liaotungensis located in North China, which show no sign of ancient introgression with Q. mongolica, form unimodal hybrid zones with Q. mongolica. These results are consistent with the hypothesis that selection against hybrids has had sufficient time to reinforce the reproductive barriers between Q. liaotungensis and Q. mongolica in Northeast China but not in North China. PMID- 22059562 TI - Microstructure of fermented sausage. AB - A protein matrix is necessary for the desired texture of fermented sausages suitable for slicing. The formation of this network is predominantly induced by myosin and actin proteins. A change in the structure of native muscle proteins results from different technological processes such as chopping, salting, and fermentation. During chopping with simultaneous release of meat proteins, the salt brings about a change in the original structure of proteins by swelling and partial solution of myofibrils. The dissolved proteins are transformed into a thin fluid colloidal transition state, the so-called 'sol-state' with unstable coagulation bonds. During sausage ripening, as a result of denaturation by lactic acid and due to gradual loss of water (drying), the unstable bonds are replaced by condensation bonds, and thus the sol-state is converted into the 'gel-state'. Both gel formation (condensation structure) and water evaporation (syneresis) result in the development of a matrix in fermented sausage and, consequently, in the texture of the sliceable product. PMID- 22059563 TI - Characteristics of some intermediate moisture smoked meats. AB - Intermediate moisture smoked beef was prepared by cook-soak/equilibration in a solution containing sodium chloride, sodium nitrite and potassium sorbate. Two further solutions contained glycerol and glycerol + 'onion' in addition to the above ingredients. Half the samples in each treatment group were smoked for 18 h (heavy smoking) and the others for 4 h (light smoking) at 50 degrees C. All samples developed the pink-red colour of nitrite cured meat but those treated with glycerol were darker, presumably due to decreased moisture contents. Glycerol increased the apparent moisture, fat and sodium dodecyl sulphate (SDS) soluble protein contents and also improved the conversion of haemoproteins to the cooked cured form but decreased the percent soluble hydroxyproline. Smoking caused a marked decrease in moisture, SDS-soluble protein and soluble hydroxyproline contents and slightly decreased the available lysine and percent conversion of the haemoproteins to the cured nitrose forms. Smoking also caused increased darkening and hardness of the samples. Total viable aerobes, coliforms and fungi were below the levels of detection while TBA values were low and all samples possessed no detectable rancidity. Electrophoretograms of the samples indicated that cooking/equilibration had no significant effects on the proteins present but smoking led to a slight loss of some of the protein components. PMID- 22059564 TI - Collagen and its rational content in meat products 2: Experiments with growing rats. AB - Experiments with growing rats have been carried out to determine the specific changes in the biological value of finely minced meat following an increase in the total ratio of collagen from 6.1% to 21.2% of the total proteins. It has been established that within the above range the biological value and net protein utilization tended to drop, the difference being statistically insignificant. At the same time, an increase in the collagen content to 14.5% did not reduce the efficiency of tissue protein biosynthesis. It has been demonstrated that the above differences in the biological value for humans and rats are due to their varied requirements for protein composition. Therefore, the results obtained do not contradict the conclusion favouring a positive effect of a 15-20% increase in the total ratio of collagen on the efficiency of utilizing meat proteins for the human body's biosynthesis. PMID- 22059565 TI - A response surface investigation of the effects of sodium chloride and tripolyphosphate on the thermal properties of beef muscle. AB - A response surface investigation, utilizing a central composite rotatable design, measured the thermal response of beef muscle samples treated with sodium chloride (NaCl, 0.5-2%) and sodium tripolyphosphate (TPP, 0.2-0.6%). Low temperature transitions were reduced in enthalpy and transition temperature by increased salt concentration. Enthalpy was raised by increased TPP levels. Total enthalpy, over the temperature range 45-90 degrees C, demonstrated the strong stabilizing effect of TPP at salt levels below 1%, and the lack of effect of TPP concentrations over 0.5% with salt levels greater than 1.25%. NaCl and TPP concentrations in excess of 1.5 and 0.4%, respectively, show little additional effect on thermal response. PMID- 22059566 TI - (31)P NMR study of post mortem changes in pig muscle. AB - The rate and the extent of post mortem pH changes in pig muscle largely determine pork quality. Fast pH fall combined with low ultimate pH leads to pale soft exudative (PSE) meat; high ultimate pH leads to dark firm dry (DFD) meat. Post mortem metabolism was studied in pig muscle using(31)P NMR. Fifteen pigs, i.e. 7 Large White pigs and 8 Pietrain pigs, were used. Five pigs of each breed were slaughtered, taking care to minimize preslaughter stress. The other pigs (3 Large Whites and 2 Pietrains) were injected with 0.1 mg adrenaline per kg liveweight before slaughter, in order to increase meat ultimate pH. All the animals were killed by electronarcosis and exsanguination. Three of the adrenaline-treated pigs (1 Large White and 2 Pietrains) gave meat with ultimate pH above 6 (DFD meat). The pigs with normal muscle ultimate pH, i.e. 6 Large Whites and 6 Pietrains, had very variable rates of post mortem muscle metabolism (pH at 30 min after slaughter: 6.17-6.85 in Large Whites; 6.04-6.23 in Pietrains). The relationships between pH and ATP changes were similar in all pigs showing normal muscle ultimate pH, whereas ATP disappeared at a high pH value (on average pH 6.4) in pigs with high ultimate pH. The course of post mortem biochemical changes in a given animal could be predicted rather well by examination of a single(31)P NMR spectrum obtained around 30 min after death. At this time, muscle with a low rate of metabolism simultaneously showed medium to high pH, high ATP content (4 6.8 MUmol/g) and rather low Pi content (6-14 MUmol/g); muscle with a fast rate of metabolism (PSE-prone muscle) had low pH, low to medium ATP content (1.1-4 MUmol/g) and generally high phosphomonoester (PME) content (9-23 MUmol/g); muscle with high ultimate pH (DFD-prone muscle) had high pH, low PME content (4-8 MUmol/g) and high Pi content (22-27 MUmol/g). PMID- 22059567 TI - Identification and evaluation of volatile compounds of vacuum and modified atmosphere packaged beef strip loins. AB - Beef strip loins were packaged and stored for up to 28 days at 3 degrees C in high-oxygen barrier film under vacuum and in 100% CO(2), 40% CO(2)/60% N(2) and 20% CO(2)/80% O(2). As storage progressed, loins packaged and stored in 20% CO(2)/80% O(2) developed strong off-odors. 1-hexene, methyl thiirane, ethyl acetate, benzene and 1-heptene were detected in these packaged loins beginning at 7 to 14 days of storage. With the exception of 1-hexene, these compounds were not consistently detected in loins stored in vacuum, in 100% CO(2), or in 40% CO(2)/60% N(2), and these packaged loins developed much less off-odor during storage than loins packaged and stored in 20% CO(2)/80% O(2). A large number of volatile compounds from the headspace of the packaged loins originated from the packaging material. Lactobacillus plantarum became the dominant flora on loins stored under vacuum and under 40% CO(2)/60% N(2) while Leuconostoc mesenteroides subsp. mesenteroides predominated in loins stored in 100% CO(2). Pseudomonas putida eventually dominated on loins stored in 20% CO(2)/80% O(2). PMID- 22059568 TI - Thermal denaturation of Turkey breast myosin under different conditions: Effect of temperature and pH, and reversibility of the denaturation. AB - The thermal denaturation and renaturation of turkey breast myosin (TBM) under different conditions of pH and temperature was evaluated by circular dichroism. TBM unfolds upon heating, and the degree of unfolding was dependent on the pH and temperature. The transition temperature (T(m)) of TBM at pH values of 6 and 12 was found to be 40 degrees C, suggesting that TBM is more temperature sensitive than other myosins. Full reversibility of the thermal denaturation of TBM was usually present when TBM was heated for 5-30 min at 40 degrees C for 5 min at 50 degrees C and incubated for 24 h at 4 degrees C. PMID- 22059569 TI - The minimum quantity of nitrite required to stain sliced and homogenised cooked pork. AB - The levels of nitrite used in curing pork are in excess of those required to produce an adequate cured colour, but the minimum level for pink coloration to be visible has not been established experimentally. This paper demonstrates the effect of low nitrite levels from local surface application to pork muscle, simulating inadvertent contamination from work surfaces. An homogenate is used for comparison in which the nitrite was evenly distributed throughout the product. The results indicate that surface contact with nitrite produces essentially the same pattern of colour change as in the homogenate. Visible pink coloration was evident from 1-2 mg kg(-1) sodium nitrite absorbed. PMID- 22059570 TI - Beta-endorphin and cortisol concentrations in plasma of blood samples collected during exsanguination of cattle. AB - Blood samples were collected during exsanguination from a group of 36 cattle slaughtered at a research abattoir and from a group of 36 cattle slaughtered at a commercial abattoir. Beta-endorphin and cortisol values were measured in plasma from all blood samples. The mean beta-endorphin values for the two groups of animals (19.2 and 20.9 pmol/litre) did not differ significantly. The mean cortisol values for the two groups of cattle did differ significantly (P < 0.001), with the commercial abattoir group having the greater mean value (123 nmol/litre versus 41 nmol/litre). Although the commercial abattoir group had an elevated mean cortisol value there were no dark cutting carcasses in the group. PMID- 22059571 TI - Effects of exogenous porcine somatotropin (pST) administration on pork meat quality. AB - Two experiments were conducted on Large White pigs in order to assess the effect of porcine somatotropin (pST) administration upon meat quality criteria. No clear trend was observed concerning pH1 or pH2 measurements in Longissimus dorsi (LD), Adductor femoris (AF) and Semi spinalis (SS) muscles or drip loss in LD. Cooking loss in LD was not affected by pST treatment. Intramuscular lipid content was decreased by pST in LD and AF. Only non-polar lipids were affected by pST, whereas polar lipid content was similar in control and pST treated pigs. Percentage polyunsaturated fatty acids was significantly increased by pST in backfat and LD lipids, whereas no clear trend was observed concerning fatty acid composition of AF lipids. PMID- 22059572 TI - Influence of dietary fat and alpha-tocopherol supplementation on lipid oxidation in pork. AB - Sixty-four pigs, approximately 3 weeks old, were fed diets containing 3% beef tallow or 3% soya oil with either a basal (10-50 mg/kg diet) or supplemented (200 mg/kg diet) level of alpha-tocopheral acetate. In pigs fed the soya oil diet the neutral and polar lipid fractions of muscle tissue and the total lipid fraction of adipose tissue had significantly (P < 0.05) higher C18:2/C18:1 ratios when compared to pigs fed the tallow diet. Muscle from pigs fed the soya oil diet was significantly more susceptible (P < 0.05) to lipid oxidation than muscle from pigs fed the tallow diet. In pigs receiving the alpha-tocopherol supplemented diet, alpha-tocopherol levels were approximately 3.3, 2.8 and 2-times higher in plasma, muscle and adipose tissue, respectively, when compared to pigs fed the basal level of alpha-tocopherol acetate. alpha-Tocopherol supplementation significantly increased (P < 0.05) the oxidative stability of muscle from pigs fed both the tallow and soya oil diets. PMID- 22059573 TI - How far and how fast can genomics take us towards precision breeding? PMID- 22059574 TI - Using the genomic relationship matrix to predict the accuracy of genomic selection. AB - Estimated breeding values (EBVs) using data from genetic markers can be predicted using a genomic relationship matrix, derived from animal's genotypes, and best linear unbiased prediction. However, if the accuracy of the EBVs is calculated in the usual manner (from the inverse element of the coefficient matrix), it is likely to be overestimated owing to sampling errors in elements of the genomic relationship matrix. We show here that the correct accuracy can be obtained by regressing the relationship matrix towards the pedigree relationship matrix so that it is an unbiased estimate of the relationships at the QTL controlling the trait. This method shows how the accuracy increases as the number of markers used increases because the regression coefficient (of genomic relationship towards pedigree relationship) increases. We also present a deterministic method for predicting the accuracy of such genomic EBVs before data on individual animals are collected. This method estimates the proportion of genetic variance explained by the markers, which is equal to the regression coefficient described above, and the accuracy with which marker effects are estimated. The latter depends on the variance in relationship between pairs of animals, which equals the mean linkage disequilibrium over all pairs of loci. The theory was validated using simulated data and data on fat concentration in the milk of Holstein cattle. PMID- 22059575 TI - Efficient computation of the genomic relationship matrix and other matrices used in single-step evaluation. AB - Genomic evaluations can be calculated using a unified procedure that combines phenotypic, pedigree and genomic information. Implementation of such a procedure requires the inverse of the relationship matrix based on pedigree and genomic relationships. The objective of this study was to investigate efficient computing options to create relationship matrices based on genomic markers and pedigree information as well as their inverses. SNP maker information was simulated for a panel of 40 K SNPs, with the number of genotyped animals up to 30 000. Matrix multiplication in the computation of the genomic relationship was by a simple 'do' loop, by two optimized versions of the loop, and by a specific matrix multiplication subroutine. Inversion was by a generalized inverse algorithm and by a LAPACK subroutine. With the most efficient choices and parallel processing, creation of matrices for 30 000 animals would take a few hours. Matrices required to implement a unified approach can be computed efficiently. Optimizations can be either by modifications of existing code or by the use of efficient automatic optimizations provided by open source or third-party libraries. PMID- 22059576 TI - The unified approach to the use of genomic and pedigree information in genomic evaluations revisited. AB - Previous proposals for a unified approach for amalgamating information from animals with or without genotypes have combined the numerator relationship matrix A with the genomic relationship G estimated from the markers. These approaches have resulted in biased genomic EBV (GEBV), and methodology was developed to overcome these problems. Firstly, a relationship matrix, G(FG) , based on linkage analysis was derived using the same base population as A, which (i) utilizes the genomic information on the same scale as the pedigree information and (ii) permits the regression coefficients used to propagate the genomic data from the genotyped to ungenotyped individuals to be calculated in the light of the genomic information, rather than ignoring it. Secondly, the elements of G were regressed back towards their expected values in the A matrix to allow for their estimation errors. These developments were combined in a methodology LDLAb and tested on simulated populations where either parents were phenotyped and offspring genotyped or vice versa. The LDLAb method was demonstrated to be a unified approach that maximized accuracy of GEBV compared to previous methodologies and removed the bias in the GEBV. Although LDLAb is computationally much more demanding than MLAC, it demonstrates how to make best use the marker information and also shows the computational problems that need to be solved in the future to make best use of the marker data. PMID- 22059577 TI - The impact of the rank of marker variance-covariance matrix in principal component evaluation for genomic selection applications. AB - In genomic selection (GS) programmes, direct genomic values (DGV) are evaluated using information provided by high-density SNP chip. Being DGV accuracy strictly dependent on SNP density, it is likely that an increase in the number of markers per chip will result in severe computational consequences. Aim of present work was to test the effectiveness of principal component analysis (PCA) carried out by chromosome in reducing the marker dimensionality for GS purposes. A simulated data set of 5700 individuals with an equal number of SNP distributed over six chromosomes was used. PCs were extracted both genome-wide (ALL) and separately by chromosome (CHR) and used to predict DGVs. In the ALL scenario, the SNP variance covariance matrix (S) was singular, positive semi-definite and contained null information which introduces 'spuriousness' in the derived results. On the contrary, the S matrix for each chromosome (CHR scenario) had a full rank. Obtained DGV accuracies were always better for CHR than ALL. Moreover, in the latter scenario, DGV accuracies became soon unsettled as the number of animals decreases, whereas in CHR, they remain stable till 900-1000 individuals. In real applications where a 54k SNP chip is used, the largest number of markers per chromosome is approximately 2500. Thus, a number of around 3000 genotyped animals could lead to reliable results when the original SNP variables are replaced by a reduced number of PCs. PMID- 22059578 TI - Use of haplotypes to estimate Mendelian sampling effects and selection limits. AB - Limits to selection and Mendelian sampling (MS) terms can be calculated using haplotypes by summing the individual additive effects on each chromosome. Haplotypes were imputed for 43 382 single-nucleotide polymorphisms (SNP) in 1455 Brown Swiss, 40 351 Holstein and 4064 Jersey bulls and cows using the Fortran program findhap.f90, which combines population and pedigree haplotyping methods. Lower and upper bounds of MS variance were calculated for daughter pregnancy rate (a measure of fertility), milk yield, lifetime net merit (a measure of profitability) and protein yield assuming either no or complete linkage among SNP on the same chromosome. Calculated selection limits were greater than the largest direct genomic values observed in all breeds studied. The best chromosomal genotypes generally consisted of two copies of the same haplotype even after adjustment for inbreeding. Selection of animals rather than chromosomes may result in slower progress, but limits may be the same because most chromosomes will become homozygous with either strategy. Selection on functions of MS could be used to change variances in later generations. PMID- 22059579 TI - Using genome-wide information to minimize the loss of diversity in conservation programmes. AB - We study here the effect of using genome-wide marker data versus genealogical data in population management for the maintenance of diversity in conservation schemes using optimal contributions. We re-examine the benefits of using molecular data for different population and genome sizes and compare different management strategies according to the group of individuals where we take decisions (parents or offspring). We also study the consequences of using estimated genealogical coancestries calculated from molecular information. Using genome-wide marker data performed usually better than using genealogical data or estimated genealogical coancestry to maintain expected and observed heterozygosity. Furthermore, when we could take decisions acting on the offspring, a larger heterozygosity was maintained than when we based our decisions on the potential parents. PMID- 22059580 TI - Maximization of total genetic variance in breed conservation programmes. AB - The preservation of the maximum genetic diversity in a population is one of the main objectives within a breed conservation programme. We applied the maximum variance total (MVT) method to a unique population in order to maximize the total genetic variance. The function maximization was performed by the annealing algorithm. We have selected the parents and the mating scheme at the same time simply maximizing the total genetic variance (a mate selection problem). The scenario was compared with a scenario of full-sib lines, a MVT scenario with a rate of inbreeding restriction, and with a minimum coancestry selection scenario. The MVT method produces sublines in a population attaining a similar scheme as the full-sib sublining that agrees with other authors that the maximum genetic diversity in a population (the lowest overall coancestry) is attained in the long term by subdividing it in as many isolated groups as possible. The application of a restriction on the rate of inbreeding jointly with the MVT method avoids the consequences of inbreeding depression and maintains the effective size at an acceptable minimum. The scenario of minimum coancestry selection gave higher effective size values, but a lower total genetic variance. A maximization of the total genetic variance ensures more genetic variation for extreme traits, which could be useful in case the population needs to adapt to a new environment/production system. PMID- 22059581 TI - Consequences for diversity when prioritizing animals for conservation with pedigree or genomic information. AB - Up to now, prioritization of animals for conservation has been mainly based on pedigree information; however, genomic information may improve prioritization. In this study, we used two Holstein populations to investigate the consequences for genetic diversity when animals are prioritized with optimal contributions based on pedigree or genomic data and whether consequences are different at the chromosomal level. Selection with genomic kinships resulted in a higher conserved diversity, but differences were small. Largest differences were found when few animals were prioritized and when pedigree errors were present. We found more differences at the chromosomal level, where selection based on genomic kinships resulted in a higher conserved diversity for most chromosomes, but for some chromosomes, pedigree-based selection resulted in a higher conserved diversity. To optimize conservation strategies, genomic information can help to improve the selection of animals for conservation in those situations where pedigree information is unreliable or absent or when we want to conserve diversity at specific genome regions. PMID- 22059582 TI - Use of a microsatellite-based pedigree in estimation of heritabilities for economic traits in Australian blue mussel, Mytilus galloprovincialis. AB - This study aimed to estimate the heritabilities of three economically important traits (total weight, shell shape and meat yield) in Australian blue mussels. The estimates were derived using a pedigree reconstructed from a suite of both published and newly developed microsatellite markers. A total of 135 microsatellite loci were tested, of which 10 loci produced consistent PCR amplification and reliable results across all samples (74 full-sibling families including 74 pairs of parents and 2536 offspring). Lack of polymorphism at the non-repetitive region of the adhesive protein gene confirmed that the broodstock were derived from a single species. A total of 1538 progenies (62.5%) could be assigned to single parent pairs, and the remainder were assigned to two families or more, so were discarded from further analysis. Heritabilities for total weight, shell shape and meat yield were low (0.051 +/- 0.027, 0.085 +/- 0.038 and 0.049 +/- 0.028, respectively) but reflected large environmental variation rather than limited genetic variation, suggesting a family-based breeding programme could improve these traits. The genetic correlation between weight and meat yield, expressed as percentage of total mussel which was not shell, was negative, while the genetic correlation between meat yield and shell shape was weakly positive. PMID- 22059583 TI - Y chromosome genetic diversity in the Lidia bovine breed: a highly fragmented population. AB - To assess the paternal gene pool in the Lidia bovine breed (or fighting bull), a total of 603 animals belonging to 81 herds classified in 33 lineages were genotyped for six Y chromosome microsatellites, one single nucleotide polymorphism and one indel. A total of 10 haplotypes were determined with a high level of frequency variation between them, ranging from 0.2 to 74%. All the haplotypes identified belong to two previously defined major haplogroups (Y1 and Y2). Two major paternal influences were identified, corresponding to the two most common haplotypes (H1Y1 and H3Y2) with frequencies of 74 and 18%, respectively. The detection of the INRA189-104 allele evidenced an African influence in the Lidia bovine breed. Low levels of haplotype diversity have been achieved and only eight lineages showed more than one haplotype. Analysis of molecular variance showed a high level of interlineage variance (F(ST) = 86%). Network results evidenced two main clusters made for those haplotypes belonging to Y1 and Y2 haplogroups, respectively. The findings support a high level of genetic structure together with a low level of genetic diversity in the Lidia bovine breed. PMID- 22059585 TI - Ionic liquid-supported aldehyde: a highly efficient scavenger for primary amines. AB - Novel aldehyde-functionalized ionic liquids have been synthesized and used as scavengers for primary amines in the synthesis of secondary amines. The yields of secondary amines are high (82-90%) with high purity. The advantages of the protocol over that with a polymer-supported aldehyde scavenger are the shorter reaction time, the homogeneous reaction medium, the high level of loading of the aldehyde group, easy monitoring of reaction, and characterization of intermediates. PMID- 22059586 TI - Letter to the editor of biometrics on "joint regression analysis for discrete longitudinal data" by Madsen and Fang. PMID- 22059587 TI - Implications of sampling design and sample size for national carbon accounting systems. AB - BACKGROUND: Countries willing to adopt a REDD regime need to establish a national Measurement, Reporting and Verification (MRV) system that provides information on forest carbon stocks and carbon stock changes. Due to the extensive areas covered by forests the information is generally obtained by sample based surveys. Most operational sampling approaches utilize a combination of earth-observation data and in-situ field assessments as data sources. RESULTS: We compared the cost efficiency of four different sampling design alternatives (simple random sampling, regression estimators, stratified sampling, 2-phase sampling with regression estimators) that have been proposed in the scope of REDD. Three of the design alternatives provide for a combination of in-situ and earth-observation data. Under different settings of remote sensing coverage, cost per field plot, cost of remote sensing imagery, correlation between attributes quantified in remote sensing and field data, as well as population variability and the percent standard error over total survey cost was calculated. The cost-efficiency of forest carbon stock assessments is driven by the sampling design chosen. Our results indicate that the cost of remote sensing imagery is decisive for the cost efficiency of a sampling design. The variability of the sample population impairs cost-efficiency, but does not reverse the pattern of cost-efficiency of the individual design alternatives. CONCLUSIONS, BRIEF SUMMARY AND POTENTIAL IMPLICATIONS: Our results clearly indicate that it is important to consider cost efficiency in the development of forest carbon stock assessments and the selection of remote sensing techniques. The development of MRV-systems for REDD need to be based on a sound optimization process that compares different data sources and sampling designs with respect to their cost-efficiency. This helps to reduce the uncertainties related with the quantification of carbon stocks and to increase the financial benefits from adopting a REDD regime. PMID- 22059588 TI - Lipopolysaccharide biosynthesis without the lipids: recognition promiscuity of Escherichia coli heptosyltransferase I. AB - Heptosyltransferase I (HepI) is responsible for the transfer of l-glycero-d-manno heptose to a 3-deoxy-alpha-D-oct-2-ulopyranosonic acid (Kdo) of the growing core region of lipopolysaccharide (LPS). The catalytic efficiency of HepI with the fully deacylated analogue of Escherichia coli HepI LipidA is 12-fold greater than with the fully acylated substrate, with a k(cat)/K(m) of 2.7 * 10(6) M(-1) s(-1), compared to a value of 2.2 * 10(5) M(-1) s(-1) for the Kdo(2)-LipidA substrate. Not only is this is the first demonstration that an LPS biosynthetic enzyme is catalytically enhanced by the absence of lipids, this result has significant implications for downstream enzymes that are now thought to utilize deacylated substrates. PMID- 22059589 TI - Responses in digestion, rumen fermentation and microbial populations to inhibition of methane formation by a halogenated methane analogue. AB - The effects of the anti-methanogenic compound, bromochloromethane (BCM), on rumen microbial fermentation and ecology were examined in vivo. Japanese goats were fed a diet of 50 % Timothy grass and 50 % concentrate and then sequentially adapted to low, mid and high doses of BCM. The goats were placed into the respiration chambers for analysis of rumen microbial function and methane and H2 production. The levels of methane production were reduced by 5, 71 and 91 %, and H2 production was estimated at 545, 2941 and 3496 mmol/head per d, in response to low, mid and high doses of BCM, respectively, with no effect on maintenance feed intake and digestibility. Real-time PCR quantification of microbial groups showed a significant decrease relative to controls in abundance of methanogens and rumen fungi, whereas there were increases in Prevotella spp. and Fibrobacter succinogenes, a decrease in Ruminococcus albus and R. flavefaciens was unchanged. The numbers of protozoa were also unaffected. Denaturing gradient gel electrophoresis and quantitative PCR analysis revealed that several Prevotella spp. were the bacteria that increased most in response to BCM treatment. It is concluded that the methane-inhibited rumen adapts to high hydrogen levels by shifting fermentation to propionate via Prevotella spp., but the majority of metabolic hydrogen is expelled as H2 gas. PMID- 22059594 TI - Compensation scheme for complementary and alternative medicine use in asbestos related diseases in New South Wales, Australia. AB - WHAT IS KNOWN AND OBJECTIVE: Asbestos use has resulted in a high global incidence rate of asbestos-related diseases (ARDs). These diseases require high costs of compensation and medical expense, although definite cures have yet to be found. Complementary and alternative medicine (CAM) has been used as a means to attenuate symptoms of ARDs. Our objective is to describe the compensation scheme for CAM use for a population with ARDs in New South Wales (NSW), Australia. COMMENT: Expenses of CAM have conditionally been compensated by the workers compensation dust-diseases board (DDB) to a population with ARDs. The DDB approves patients' claim for the use of CAM if it is justifiable and related to compensable ARDs. To obtain the DDB's approval for the CAM cost, a written recommendation letter by the treating medical doctors is required that justifies the use of CAM and that this option does not pose any adverse effects on the compensated patients. WHAT IS NEW AND CONCLUSION: The use of CAM in a subject with ARDs does not have significant benefits of overall survival but does somewhat improve quality of life. However, awareness of the provisions of the compensation scheme for CAM use in a population with ARDs should be carefully informed and also emphasized any side effects on progress of ARDs. PMID- 22059595 TI - Influence of cell surface structures on crenarchaeal biofilm formation using a thermostable green fluorescent protein. AB - The thermoacidophilic crenarchaeote Sulfolobus acidocaldarius displays three distinct type IV pili-like structures on its surface: (i) the flagellum, (ii) the UV-induced pili and (iii) the adhesive pili. In bacteria, surface appendages play an important role in the spatial organization of cells from initial surface attachment to the development of mature community structures. To investigate the influence of the diverse set of type IV pili-like structures in S. acidocaldarius, single, double and triple mutants lacking the cell surface appendages were constructed and analysed for their behaviour in attachment assays and during biofilm formation. A heat stable green fluorescent protein was employed the first time in a hyperthermophilic archaeon. A codon adjusted eCGP123 was expressed to study mixed biofilms of different deletion mutants to understand the interplay of the surface structures during biofilm formation. During this process the deletion of the adhesive pili and UV-induced pili led to the most pronounced effects, either an increase in cell density or increased cluster formation respectively. However, all three cell surface appendages played a role in the colonization of surfaces and only the interplay of all three appendages leads to the observed wild-type biofilm phenotype. PMID- 22059596 TI - Arabidopsis lonely guy (LOG) multiple mutants reveal a central role of the LOG dependent pathway in cytokinin activation. AB - Cytokinins are phytohormones that play key roles in the maintenance of stem cell activity in plants. Although alternative single-step and two-step activation pathways for cytokinin have been proposed, the significance of the single-step pathway which is catalyzed by LONELY GUY (LOG), is not fully understood. We analyzed the metabolic flow of cytokinin activation in Arabidopsis log multiple mutants using stable isotope-labeled tracers and characterized the mutants' morphological and developmental phenotypes. In tracer experiments, cytokinin activation was inhibited most pronouncedly by log7, while the other log mutations had cumulative effects. Although sextuple or lower-order mutants did not show drastic phenotypes in vegetative growth, the log1log2log3log4log5log7log8 septuple T-DNA insertion mutant in which the LOG-dependent pathway is impaired, displayed severe retardation of shoot and root growth with defects in the maintenance of the apical meristems. Detailed observation of the mutants showed that LOG7 was required for the maintenance of shoot apical meristem size. LOG7 was also suggested to play a role for normal primary root growth together with LOG3 and LOG4. These results suggest a dominant role of the single-step activation pathway mediated by LOGs for cytokinin production, and overlapping but differentiated functions of the members of the LOG gene family in growth and development. PMID- 22059597 TI - sigma/sigma- And pi/pi-interactions are equally important: multilayered graphanes. AB - The properties of single-sheet [n]graphanes, their double-layered forms (diamondoids), and their van der Waals (vdW) complexes (multilayered [n]graphanes) were studied for n = 10-97 at the dispersion-corrected density functional theory (DFT) level utilizing B97D with a 6-31G(d,p) basis set; for comparison, we also computed a series of structures at M06-2X/6-31G(d,p) as well as B3LYP-D3/6-31G(d,p) and evaluated SCS-MP2/cc-pVDZ single-point energies. The association energies for the vdW complexes reach 120 kcal mol(-1) already at 2 nm particle size ([97]graphane dimer), and graphanes adopt layered structures similar to that of graphenes. The association energies of multilayered graphanes per carbon atom are rather similar and independent of the number of layers (ca. 1.2 kcal mol(-1)). Graphanes show quantum confinement effects as the HOMO-LUMO gaps decrease from 8.2 eV for [10]graphane to 5.7 eV for [97]graphane, asymptotically approaching 5.4 eV previously obtained for bulk graphane. Similar trends were found for layered graphanes, where the differences in the electronic properties of double-sheet CH/sigma vdW and double-layered CC/sigma diamondoids vanish at particles sizes of 1 nm. For comparison, we studied the parent CC/pi systems, i.e., the single- and double-sheet [n]graphenes (n = 10-130) for which the association energies demonstrate the same trends as in the case of [n]graphanes; in both cases the band gaps decrease with an increase in system size. The [112]graphene dimer (HOMO-LUMO gap = 0.5 eV) already approaches the 2D metallic properties of graphite. PMID- 22059598 TI - Mental distress, alcohol use and help-seeking among medical and business students: a cross-sectional comparative study. AB - BACKGROUND: Stress and distress among medical students are thoroughly studied and presumed to be particularly high, but comparative studies including other student groups are rare. METHODS: A web-based survey was distributed to 500 medical students and 500 business students. We compared levels of study stress (HESI), burnout (OLBI), alcohol habits (AUDIT) and depression (MDI), and analysed their relationship with self-assessed mental health problems by logistic regression, with respect to gender. RESULTS: Medical students' response rate was 81.6% and that of business students 69.4%. Business students scored higher on several study stress factors and on disengagement. Depression (OR 0.61, CI95 0.37;0.98) and harmful alcohol use (OR 0.55, CI95 0.37; 0.75) were both less common among medical students. However, harmful alcohol use was highly prevalent among male students in both groups (medical students 28.0%, business students 35.4%), and among female business students (25.0%). Mental health problems in need of treatment were equally common in both groups; 22.1% and 19.3%, respectively, and was associated with female sex (OR 2.01, CI95 1.32;3.04), exhaustion (OR 2.56, CI95 1.60;4.10), lower commitment to studies (OR 1.95, CI95 1.09;3.51) and financial concerns (OR 1.81 CI95 1.18;2.80) CONCLUSIONS: Medical students may not be more stressed than other high achieving student populations. The more cohesive structure of medical school and a higher awareness of a healthy lifestyle may be beneficial factors. PMID- 22059599 TI - Effect of dietary nitrogen content on the urine metabolite profile of dairy cows assessed by nuclear magnetic resonance (NMR)-based metabolomics. AB - NMR-based metabolomics was applied on urine samples from 32 cows that were fed four levels of crude protein (124, 135, 151, and 166 g/kg DM, respectively) in a crossover design with the aim of identifying urinary metabolites related to nitrogen intake and nitrogen efficiency. Principal component analysis (PCA) on selected regions of the obtained (1)H NMR spectra revealed an effect of crude protein intake on NMR signals in the 0.5-3.0 and 5.0-10.0 ppm regions. Partial least-squares (PLS) regressions confirmed a correlation between the NMR metabolite profile and both nitrogen intake and efficiency. The NMR signals that correlated with nitrogen intake and efficiency included urea, hippurate, phenylacetylglutamine, and p-cresol sulfate, which all contributed to the prediction of nitrogen intake and efficiency. Thus, it was not possible to identify a single metabolite that could be used as a marker to predict nitrogen efficiency, and it can be concluded that a wide-ranging urinary metabolite profile is needed to evaluate nitrogen efficiency in ruminants. PMID- 22059600 TI - One-legged endurance training: leg blood flow and oxygen extraction during cycling exercise. AB - AIM: As a consequence of enhanced local vascular conductance, perfusion of muscles increases with exercise intensity to suffice the oxygen demand. However, when maximal oxygen uptake (VO(2)max) and cardiac output are approached, the increase in conductance is blunted. Endurance training increases muscle metabolic capacity, but to what extent that affects the regulation of muscle vascular conductance during exercise is unknown. METHODS: Seven weeks of one-legged endurance training was carried out by twelve subjects. Pulmonary VO(2) during cycling and one-legged cycling was tested before and after training, while VO(2) of the trained leg (TL) and control leg (CL) during cycling was determined after training. RESULTS: VO(2) max for cycling was unaffected by training, although one legged VO(2) max became 6.7 (2.3)% (mean +/- SE) larger with TL than with CL. Also TL citrate synthase activity was higher [30 (12)%; P < 0.05]. With the two legs working at precisely the same power during cycling at high intensity (n = 8), leg oxygen uptake was 21 (8)% larger for TL than for CL (P < 0.05) with oxygen extraction being 3.5 (1.1)% higher (P < 0.05) and leg blood flow tended to be higher by 16.0 (7.0)% (P = 0.06). CONCLUSION: That enhanced VO(2) max for the trained leg had no implication for cycling VO(2) max supports that there is a central limitation to VO(2) max during whole-body exercise. However, the metabolic balance between the legs was changed during high-intensity exercise as oxygen delivery and oxygen extraction were higher in the trained leg, suggesting that endurance training ameliorates blunting of leg blood flow and oxygen uptake during whole-body exercise. PMID- 22059601 TI - Spin-state dependent radical stabilization in nitrenes: the unusually small singlet-triplet splitting in 2-furanylnitrene. AB - Geometries and energies of the triplet and singlet states of 2-furanylnitrene and 3-furanylnitrene have been calculated by using spin-flip coupled-cluster methods. Calculations with triple-zeta basis sets predict a singlet-triplet splitting of 10.9 kcal/mol for 2-furanylnitrene, 4.5 kcal/mol smaller than that in phenylnitrene. In contrast, the singlet-triplet splitting in 3-furanylnitrene is computed to be 1.9 kcal/mol larger than that in phenylnitrene. The differences in the singlet-triplet splittings for the furanylnitrenes are attributed to the differences in the radical stabilizing abilities of the 2-furanyl- and 3-furanyl groups compared to a phenyl ring. Comparison of the singlet-triplet splittings of more than 20 substituted aromatic nitrenes and the radical stabilizing ability of the aromatic systems reveals a high degree of correlation between the singlet triplet splitting and the radical stabilizing ability, indicating that singlet states of aromatic nitrenes are preferentially stabilized by radical stabilizing substituents. The preferential stabilization of the singlet states is attributed to the decrease in electron pair repulsion resulting from increased delocalization of the radical electron. PMID- 22059603 TI - Editorial. PMID- 22059602 TI - Targeting cognitive deficits in schizophrenia: a review of the development of a new class of medicines from the perspective of community mental health researchers. AB - INTRODUCTION: Schizophrenia is a chronic disorder associated with positive and negative symptoms and wide-ranging deficits in neurocognitive function. Neurocognitive deficits are considered to be the core pathophysiological symptoms of the illness. Neurocognitive deficits are also closely associated with functional outcome. At present, cognitive deficits remain one of the most important unmet therapeutic needs in schizophrenia. AREAS COVERED: Neuroscientific discoveries over the past decades have enriched our understanding of the neurobiological mechanism underlying cognitive deficits in schizophrenia. This research has identified new molecular mechanisms and processes as promising pharmacological targets. However, in spite of extensive efforts to develop a new class of cognitive-enhancing medicines for the treatment of schizophrenia over the past 5 years, no novel pharmacological agents have received the regulatory approvals required by the Food and Drug Administration. The efficacy and safety outcomes from selective Phase II clinical trials are reviewed. EXPERT OPINION: The evolving concept of neurocognition and the current guidelines for the design and methodology of clinical trials of cognitive-enhancing drugs for the treatment of individuals with schizophrenia are critically examined. The future directions in the development of cognitive-enhancing medicines for the treatment of schizophrenia from the perspective of clinicians and researchers from community mental health settings are discussed. PMID- 22059604 TI - Effect of dietary vitamin E on pigment and lipid stability of frozen beef: A kinetic analysis. AB - The effect of vitamin E supplementation on pigment and lipid stability was evaluated with beef wrapped in high or low oxygen permeability films and stored in the dark or under constant illumination at -20 degrees C. Dietary vitamin E supplementation improved pigment and lipid stability in both cases. Illumination increased metmyoglobin accumulation but did not affect lipid oxidation rate in both control and supplemented beef. A predisplay dark storage period of 30 days delayed metmyoglobin accumulation during subsequent display. Kinetic analysis showed that vitamin E supplementation stabilized the oxymyoglobin complex by enhancing the deoxymyoglobin oxygenation rate and by decreasing oxymyoglobin autoxidation rate. PMID- 22059605 TI - Inhibition of Listeria monocytogenes by Lactobacillus sake strains of meat origin. AB - The ability of two Lactobacillus sake strains of meat origin to inhibit the growth of Listeria monocytogenes at 4, 8, 15, 24 and 32 degrees C in a conventional liquid media was investigated. Growth of L. monocytogenes was affected by Lac. sake strains at all temperatures. The inhibition was higher at 15, 24 and 32 degrees C than at refrigeration temperatures. The inhibitory activity of both lactobacilli was similar perhaps due to the fact that Lac. sake 148 produces a bacteriocin inhibitory to L. monocytogenes, while Lac. sake 23 is a strong lactic acid producer. The antagonism exhibited by the lactobacilli on the L. monocytogenes strains seems to display a bacteriostatic rather than a bacteriocidal effect. PMID- 22059606 TI - Incorporation of sardine surimi in Bologna sausage containing different fat levels. AB - The object of this research was to assess the effects produced on binding properties, texture and microstructure by the incorporation of varying proportions of sardine surimi (0%, 6.5%, 13% and 20%) as an ingredient in Bologna sausage containing various levels of fat (4.8%, 10.6% and 20.8%). When the fat level is reduced, there is a significant decline both the in binding properties and in the shear force and penetration force of the products. These phenomena are consistent with the formation of microstructures presenting a less dense matrix. The incorporation of surimi produces scarcely any alteration in the fat and water binding properties and the rheological characteristics of meat products. PMID- 22059607 TI - Aroma components from dried sausages fermented with Staphylococcus xylosus. AB - Sausages with and without Staphylococcus xylosus were manufactured with four replicates. Antibiotics and a fungicide to inhibit growth of naturally occuring microorganisms were added to the control sausages. The volatile compounds from the sausages were collected and identified by gas chromatography/mass spectrometry, the effluent evaluated by sniffing and the sausages assessed by a trained panel. The study showed that sausages fermented with Staphylococcus xylosus contained several fragrant esters that were not found in control sausages without microbial growth. Control sausages had an unpleasant, rancid odour compared to sausages with Staphylococcus xylosus, indicating that the esterase activity of Staphylococcus xylosus or other microorganisms is very important in order to obtain the proper fermented sausage aroma. Although sausages with Staphylococcus xylosus contained the highest amounts of free fatty acids, it seemed to be of no importance to the aroma development. It is therefore questionable whether lipolytic activity of starter cultures has any influence on sausage flavour. PMID- 22059608 TI - Growth, composition and eating quality of Longissimus dorsi from young bulls fed the beta-agonist cimaterol at consecutive developmental stages. AB - The objective was to investigate the effect of the beta-adrenergic agonist, cimaterol, on gain, composition and meat quality of primerib (M. longissimus dorsi) from Friesian young bulls slaughtered at different developmental stages. Twelve pairs of monozygotic twins were allocated to three liveweight (LW) groups (162, 299 and 407 kg, respectively). Within each pair, one animal was given 0.056 mg cimaterol per kg LW for 90 days, while the other served as a control. Cimaterol treatment increased the estimated gain and the weight of primerib by 55 and 20%, respectively (both P < 0.001), and lean and protein content of the longissimus dorsi muscle by 26 and 25%, respectively (both P < 0.001), and concomitantly reduced fat content of primerib by 16% (P < 0.01) and intramuscular fat in longissimus dorsi by 36% (P < 0.001). Cimaterol treatment reduced total collagen content (P < 0.02), but not collagen solubility (P > 0.55). Meat colour was slightly lighter (lightness, P < 0.06), but pH(24) and pH(final) was not affected by cimaterol. Cimaterol increased Volodkevich shear force values (P < 0.001). In general, the effect of cimaterol on meat quality characteristics was evident in all three LW groups, and LW only affected percent fat in primerib, intramuscular fat content in longissimus dorsi, meat colour and absolute contents of protein, fat and bone. PMID- 22059609 TI - Prediction of sensory characteristics of beef by near-infrared spectroscopy. AB - Sensory hardness, tenderness and juiciness of M. Longissimus dorsi muscles from 10 beef carcasses at three ageing stages were predicted by near-infrared (NIR) spectroscopic analysis in the reflection (NIRR) and transmission modes (NIRT) during 14 days ageing at 2 degrees C. Predicting the sensory variables hardness and tenderness from NIRR measurements using principal component regression (PCR), yielded correlation coefficients in the range 0.80-0.90. The root mean square errors of prediction for the predictions of hardness and tenderness were in the range 0.5-0.7, given in sensory assessment units. Juiciness was not well predicted. Prediction of sensory variables from NIRT measurements did not give satisfactory results. Including samples from all carcasses, cows and young bulls in the models resulted in good predictions from NIRR measurements of frozen and thawed samples. However, the best prediction results were generally obtained from separate calibrations of the samples from the bulls. The potential of NIR spectroscopy in the prediction of sensory variables in whole meat needs to be further investigated on a larger number of samples with different breeds, animals and process treatments included. PMID- 22059610 TI - Performance characteristics of three different pre-evisceration wash regimes applied to the forequarters of ovine carcasses in an inverted dressing system. AB - The performance of three pre-evisceration wash regimes applied to the forequarters of ovine carcasses in an inverted dressing system was assessed. Washing regimes consisted of a high-pressure jet wash, a low-pressure sluice wash, and both washes applied in series. Visible contamination incidences prior to the wash were between 64 and 71% at the carcass level; wool was the predominant contaminant, while faecal material and ingesta were rare. All wash regimes reduced the incidence of carcass contamination by 62.8 to 70.5%, primarily through the removal of wool. A secondary effect was the redistribution of some wool from other areas of the forequarter to the inside leg. The sluice wash was superior to the jet wash in removing visible contamination. Bacterial numbers ranged from 3.64 to 4.03 log(10)CFU/cm(2) prior to washing and were reduced to between 3.24 and 3.75 log(10)CFU/cm(2) immediately after the pre evisceration wash; the three wash regimes performed in an equivalent, but commercially non-significant manner. Further reductions of between 0.20 and 0.58 log(10)CFU/cm(2) were effected by post-dressing events, including 12 h chilling. The low-pressure wash performance was considered superior to that of the jet wash, and no further improvement in carcass quality was demonstrated by the use of both washes in series. PMID- 22059611 TI - Muscle glycogen depletion pattern in halothane-gene-free pigs at slaughter and its relation to meat quality. AB - Muscle fibre type composition and glycogen depletion pattern at slaughter as related to meat quality, were studied in M. longissimus dorsi of halothane-gene free Swedish Yorkshire pigs fed a high (n=19; 10 entire males and 9 gilts) or a low (n=18; 10 entire males and 8 gilts) protein diet. The muscle consisted of, on average, 8% type I, 9% type IIA and 83% type IIB fibres. Muscle fibre areas were significantly smaller in entire male pigs than in gilts irrespective of fibre type. There were no marked differences in muscle characteristics between pigs fed the low and high protein diets. Low glycogen concentrations were found in most type I and type IIA muscle fibres, while a greater variation in glycogen content was evident in type IIB fibres. The pigs were divided into two groups according to the proportion of glycogen depleted IIB fibres (more or less than 30% depleted IIB fibres). In the group where 30% or more of the type IIB fibres were glycogen depleted, a tendency toward DFD meat (dry, firm, dark) was seen, as the meat had higher ultimate pH (5.62 vs 5.52; p=0.02), lower drip loss (2.7% vs 4.4%; p=0.007) and lower reflectance value (darker meat; 16.5 vs 20.6 EEL units; p=0.0005), compared with the group with less than 30% depleted IIB fibres. No difference in total glycogen content was found between these two groups. This indicates that the distribution of glycogen in different fibre types seems to be of importance for the ultimate meat quality. PMID- 22059612 TI - Mechanical and microstructural characteristics of meat doughs, either heated by a continuous process in a radio-frequency field or conventionally in a waterbath. AB - Meat doughs, all having the same chemical composition, were pasteurised to a comparable heat intensity (calculated as Cook values: target level of 5 min at 100 degrees C): (i) while flowing through a glass tube (inner diameter 50 mm) mounted in a special radio-frequency (27 MHz) heating section; (ii) after flowing unheated through the glass tube at the same rate and heated in a waterbath; and (iii) after sampling immediately after the pump and heated in a waterbath. The cooked products were sampled in the core and at the rim of the product for rheological (oscillation and uniaxial compression tests at small strain), fracture measurements (uniaxial compression tests at high strain) and microstructural evaluation (light microscopy and video image analysis). Additional core samples were used for a sensory evaluation (triangle tests) of the texture of the differently processed doughs. The fast heating rate (25-30 K/min) at a mass flow of the dough of 100 kg/h (mean velocity 0.014 m/s) during dielectrical pasteurisation affected the mechanical character, the microstructure and the triangle test results of core samples from the sausages, compared to heating in a waterbath. Flow of the unheated dough through the tube of the continuous processing equipment, followed by heating in a waterbath, had little effect on the results of the mechanical tests, the microscopical evaluation and the triangle tests. The radio-frequency heated products had both higher storage and loss moduli (were more firm), fractured at higher stress values and were considered more firm in the sensory evaluation. The microstructure of dielectrically heated versus other samples displayed a more open structure of the protein matrix with larger irregularly shaped fat particles that were surrounded by relatively thin and compact protein bridges. The effects of flow and heating method on the behaviour of rim samples were very similar to their effects on the core of the products. A comparison of the mechanical behaviour of core and rim samples only was significant for radio-frequency heated doughs. The rim samples had lower storage and loss moduli and fractured at lower stress values than the core samples. Micrographs of the dielectrically heated rim versus core samples displayed more orientation of connective tissue particles in the direction of flow and of elongated, larger and irregularly shaped fat particles. Probably, shear at the wall of the tube affected the characteristics of the rim samples. All heated doughs displayed hardly and cooking losses. The radio-frequency heated products always displayed a thin layer of moisture on their surface and occasionally a little fat separation. PMID- 22059613 TI - Relationship between cathepsin B activity and compositional parameters in dry cured hams of normal and defective texture. AB - Thirty-eight Italian dry-cured hams were analysed for cathepsin B activity, proximate composition and proteolysis index and results were related to lean tissue texture, as assessed by an expert panel, in order to search for relationships between excessive softness, a major problem in the raw ham industry, and chemical parameters. Softness was found to be related to protein breakdown which, in turn, was linked with higher residual cathepsin B activity and, to a lesser extent, to lower salt content. Results suggest that the use of raw ham of controlled enzyme activity would improve the texture quality of the end product. PMID- 22059614 TI - Fatty acids in the subcutaneous adipose tissue of intensively fed SA Mutton Merino and Dorper wethers. AB - Recent ambiguity about the role of animal fat in causing coronary heart disease, coupled with the controversy regarding the effect of various levels of energy nutrition on ruminant depot fats, prompted an investigation into the influence of high-energy nutrition, breed and slaughter weight on the fatty acid profiles of ruminants. Two isonitrogenous and isomineral diets containing 11.76 MJ ME/kg DM and 10.18 MJ ME/kg DM were fed to Dorper and SA Mutton Merino wethers of +/- 20 kg to 37 and 43 kg live weight. Subcutaneous fat samples and feed samples were collected for fatty acid analysis. Treatment significantly affected the subcutaneous fatty acid profiles of wethers, which includes C15:0, C16:0, C17:0, C17:1, C18:0, C18:1, C18:2 and C18:3. Treatment also influenced the concentration of saturated and unsaturated fatty acids in the subcutaneous adipose tissue as well as the concentration of trans-fatty acids. The results obtained suggest that dietary energy levels may significantly affect the fatty acids in the subcutaneous fat of wethers. Breed differences, after correcting for carcass fatness, occurred in C16:0. PMID- 22059615 TI - Calcium chloride in vitro effects on isolated myofibrillar proteins. AB - The objective of this study was to determine the effect of 30 mM CaCl(2) on the solubilization of those structural proteins that contribute to myofibril stability. Ovine M. longissimus dorsi (longissimus) samples were obtained immediately post-exsanguination, myofibrils were isolated, glycerated, and frozen until needed. Myofibrils were washed, diluted and incubated in 0.1 m KCl, 10 mm Tris, pH 7.0 buffer for 24, 48 and 72 h. Treatments consisted of: (1) control, (2) 1 mm E(64), (3) 30 mm CaCl(2), and (4) 1 mm E(64) + 30 mm CaCl(2). Results (SDS-PAGE) indicated that myosin heavy chain (though not to a great extent), M protein, C-protein, alpha-actinin, actin, troponin-T, tropomyosin isoforms, troponin-I and 72, 70, 62, 33, 32, 30, and 22 kDa unidentified bands were solubilized from myofibrils incubated in KCl buffer for 72 h. The addition of CaCl(2) hastened the appearance of some of the proteins in the supernatant fractions, but no differences were observed at 72 h among the treatments. The addition of E(64) had no effect on which proteins were released. Thus, in the absence of proteolysis it appears that a general solubilization of thick-and-thin filament ancillary proteins occurs in the presence of 30 mm CaCl(2). However, the contribution to tenderness should be minimal, because solubilized proteins are not part of the cytoskeletal elements that are responsible for maintaining structural integrity of the tissue. PMID- 22059616 TI - Stability of haem pigments in model systems and cooked meat. AB - The stability of sheep haemoglobin and myoglobin in aqueous solution at 80, 100 and 121 degrees C for 1 h was measured by subjecting portions of the heated solutions to electrospray mass spectrometry (ESMS). ESMS dissociates haem proteins into the globin chains and the haem moiety and, with haemoglobin, degradation of the alpha-(15047.5 Da) and beta-(16073.3 Da) chains was observed at all heating temperatures. Under the same conditions, sheep myoglobin dissociated into the globin (16923.2 Da) and haem parts but the globin was stable and few degradation products were observed in the ESMS trace (mass range 4-20 kDa) even after 1 h at 121 degrees C. There did seem to be limited breakdown of the globin due to loss of 170 Da. From the amino acid sequence, it is postulated that this is due to loss of GLY-LEU from the N-terminus. Methods for extracting myoglobin from raw and cooked meat were then investigated. Water was adequate for myoglobin extraction from raw meat but urea solution was required for adequate extraction of cooked meat samples. Sheep meat was heated at 80, 100 and 121 degrees C in sealed cans, extracted and the mass profile in the range 4-20 kDa measured. Myoglobin was the major peak when samples were heated for 10, 20, 30 and 40 min. After that time, other peaks appeared although the myoglobin globin chain was still apparent. The results are discussed in relation to using myoglobin as a marker for meat speciation. PMID- 22059617 TI - HIV/AIDS-related institutional mistrust among multiethnic men who have sex with men: effects on HIV testing and risk behaviors. AB - OBJECTIVE: To investigate relationships between institutional mistrust (systematic discrimination, organizational suspicion, and conspiracy beliefs), HIV risk behaviors, and HIV testing in a multiethnic sample of men who have sex with men (MSM), and to test whether perceived susceptibility to HIV mediates these relationships for White and ethnic minority MSM. METHOD: Participants were 394 MSM residing in Central Arizona (M age = 37 years). Three dimensions of mistrust were examined, including organizational suspicion, conspiracy beliefs, and systematic discrimination. Assessments of sexual risk behavior, HIV testing, and perceived susceptibility to HIV were made at study entry (T1) and again 6 months later (T2). RESULTS: There were no main effects of institutional mistrust dimensions or ethnic minority status on T2 risk behavior, but the interaction of systematic discrimination and conspiracy beliefs with minority status was significant such that higher levels of systematic discrimination and more conspiracy beliefs were associated with increased risk only among ethnic minority MSM. Higher levels of systematic discrimination were significantly related to lower likelihood for HIV testing, and the interaction of organizational suspicion with minority status was significant such that greater levels of organizational suspicion were related to less likelihood of having been tested for HIV among ethnic minority MSM. Perceived susceptibility did not mediate these relationships. CONCLUSION: Findings suggest that it is important to look further into the differential effects of institutional mistrust across marginalized groups, including sexual and ethnic minorities. Aspects of mistrust should be addressed in HIV prevention and counseling efforts. PMID- 22059618 TI - An application of the theory of planned behavior--a randomized controlled food safety pilot intervention for young adults. AB - OBJECTIVE: Approximately 48 million Americans are affected by foodborne illness each year. Evidence suggests that the application of health psychology theory to food safety interventions can increase behaviors that reduce the incidence of illness such as adequately keeping hands, surfaces and equipment clean. This aim of this pilot study was to be the first to explore the effectiveness of a food safety intervention based on the Theory of Planned Behavior (TPB). METHODS: Young adult participants (N = 45) were randomly allocated to intervention, general control or mere measurement control conditions. Food safety observations and TPB measures were taken at baseline and at 4-week follow-up. Within and between group differences on target variables were considered and regression analyses were conducted to determine the relationship between condition, behavior and the TPB intention constructs; attitude, subjective norm, perceived behavioral control (PBC). RESULTS: TPB variables at baseline predicted observed food safety behaviors. At follow-up, the intervention led to significant increases in PBC (p = .024) and observed behaviors (p = .001) compared to both control conditions. Furthermore, correlations were found between observed and self-reported behaviors (p = .008). CONCLUSIONS: The pilot intervention supports the utility of the TPB as a method of improving food safety behavior. Changes in TPB cognitions appear to be best translated to behavior via behavioral intentions and PBC. Further research should be conducted to increase effectiveness of translating TPB variables to food safety behaviors. The additional finding of a correlation between self-reported and observed behavior also has implications for future research as it provides evidence toward the construct validity of self-reported behavioral measures. PMID- 22059619 TI - A longitudinal investigation of the impact of disordered eating on young women's quality of life. AB - OBJECTIVE: The extent to which subclinical levels of disordered eating affect quality of life (QOL) was assessed. METHOD: Four waves of self-report data from Survey 2 (S2) to 5 (S5) of a national longitudinal survey of young Australian women (N = 9,688) were used to assess the impact of any level of disordered eating at S2 on QOL over the following 9 years, and to evaluate any moderating effects of social support and of depression. RESULTS: At baseline, 23% of the women exhibited some level of disordered eating, and they scored significantly lower on both the physical and the mental component scores of the SF-36 at every survey; differences in mental health were still clinically meaningful at S5. Social support and depressive symptoms each acted as a moderator of the mental component scores. Women with both disordered eating and low social support, or disordered eating and depression, had the worst initial scores; although they improved the most over time, they still had the lowest scores at S5. Higher social support at baseline resulted in women with disordered eating being largely indistinguishable from women without disordered eating who had low social support. Lower levels of depression resulted in women with disordered eating having a significantly better QOL than women with high levels of depression, regardless of eating status. CONCLUSIONS: This is the first study to examine the long-term impact of subclinical levels of disordered eating on QOL, and it suggests that even apparently minor levels of symptomatology are associated with significant and far-reaching deficits in well-being. PMID- 22059620 TI - Socioeconomic status, psychosocial resources and risk, and cardiometabolic risk in Mexican-American women. AB - OBJECTIVES: The current study examined the contributions of psychosocial factors to the association between socioeconomic status (SES) and metabolic syndrome (MetSyn) risk, in a randomly selected community cohort of 304 middle-aged (40-65 years old) Mexican-American women, a population at elevated cardiometabolic risk. METHODS: Participants underwent a clinical exam and measures of demographic factors and psychosocial resource (i.e., personal and social resources) and risk (i.e., negative emotions and cognitions) variables. Confirmatory factor analysis (CFA) and structural equation models (SEMs) were performed in the total sample and in more- and less-U.S.-acculturated women (defined by language preference) separately. RESULTS: CFAs revealed single latent constructs for SES (i.e., income, education) and psychosocial resources/risk. Three-factor solution was identified, with blood pressure (systolic diastolic), lipids (high-density lipoprotein cholesterol triglycerides), and metabolic variables (glucose waist circumference) forming separate factors. SEMs showed that an indirect effects model with SES relating to MetSyn factors through psychosocial resources/risk provided a reasonable descriptive and statistical fit in the full and more acculturated sample (root mean square error of approximation [RMSEA] and standardized root-mean-square residual < .08); fit in the less-acculturated sample was marginal according to RMSEA = .09. A significant mediated path from low SES to higher waist circumference/fasting glucose via lower psychosocial resources/higher psychosocial risk was identified in the overall and more acculturated samples (p < .05). CONCLUSIONS: In this cohort of healthy, middle aged Mexican-American women, contributions of psychosocial factors to SES-MetSyn associations were limited to the core underlying metabolic mechanisms, and to more-U.S.-acculturated women. PMID- 22059621 TI - A systematic review of psychological interventions for adolescents and young adults living with chronic illness. AB - OBJECTIVE: There is increasing recognition that adolescents and young adults (AYAs) with chronic illnesses experience common psychological challenges. This article reviewed published psychological interventions for AYAs with cancer, diabetes, juvenile idiopathic arthritis, sickle cell disease, and asthma. Common, efficacious intervention components were examined to generate clearer recommendations for future age-appropriate, evidence-based intervention development. METHODS: Five databases including MEDLINE, MEDLINE In Process & Non Indexed Citations, PsycINFO, EMBASE, and CINAHL, were searched for studies involving AYAs aged 10-30 years, using quantitative two-group methods, published from 1979-2010. Of 1,233 abstracts, 87 were extracted for further analysis and a final 25 studies were eligible for inclusion. Thirteen of these studies included AYAs with diabetes, 7 studies involved AYAs with cancer, and 5 included AYAs with other illnesses. RESULTS: Educational interventions showed some significant positive results, particularly when targeted knowledge outcomes were measured. Several skills-based programs, some including parents, showed positive results, with moderate effect sizes. Interventions which taught communication skills, incorporated practical components (e.g., role-plays, homework), involved >=6 sessions, and spanned at least 3 months in length, appeared more likely to achieve positive outcomes. CONCLUSIONS: Skills-based interventions delivered over multiple sessions may yield the most positive results in AYAs with chronic illness. Given the few peer-support groups eligible for review, their efficacy remains unclear. This review points to the need for intervention development that teaches adaptive coping skills, is grounded in theoretical frameworks, and adheres to strict randomization and independent assessments to evaluate efficacy in assisting AYAs adjust to chronic illness. PMID- 22059622 TI - The multidimensional nature of perceived barriers: global versus practical barriers to HPV vaccination. AB - OBJECTIVE: Perceived barriers are one of the strongest determinants of health behavior. The current study presents a novel conceptualization of perceived barriers by testing the following hypotheses: (a) perceived barriers are multidimensional and thus should cluster into distinct factors; (b) practical barriers should be salient for individuals intending to engage in a particular health behavior, whereas global barriers should be salient for individuals not intending to enact the behavior; and (c) whereas global barriers should be negatively associated with behavioral intentions, practical barriers should be positively related to intentions. METHODS: The context for this investigation was young adult women's perceived barriers to human papillomavirus (HPV) vaccination. Two months after viewing an educational video about HPV vaccination, women (aged 18-26) who had not received any doses of the HPV vaccine (n = 703) reported their perceived barriers to HPV vaccination and intentions to receive the vaccine. RESULTS: Relative to the conventional single-factor approach, a five-factor model provided a better fit to the data and accounted for a larger proportion of variance in vaccination intentions. The relative salience of different perceived barriers varied as a function of women's intentions. Participants who were not intending to get vaccinated cited global concerns about vaccine safety and low perceived need for the vaccine. In contrast, participants intending to get vaccinated cited practical concerns (cost, logistical barriers) related to carrying out their intentions. Moreover, whereas global perceived barriers were associated with lower intentions, practical barriers were associated with higher intentions. CONCLUSIONS: Perceived barriers are multidimensional and vary systematically as a function of people's behavioral intentions. PMID- 22059623 TI - Validation of a quantitative and confirmatory method for residue analysis of aminoglycoside antibiotics in poultry, bovine, equine and swine kidney through liquid chromatography-tandem mass spectrometry. AB - The use of aminoglycoside antibiotics in food animals is approved in Brazil. Accordingly, Brazilian food safety legislation sets maximum levels for these drugs in tissues from these animals in an effort to guarantee that food safety is not compromised. Aiming to monitor the levels of these drugs in tissues from food animals, the validation of a quantitative, confirmatory method for the detection of residues of 10 aminoglycosides antibiotics in poultry, swine, equine and bovine kidney, with extraction using a solid phase and detection and quantification by LC-MS/MS was performed. The procedure is an adaptation of the US Department of Agriculture, Food Safety and Inspection Service (USDA-FSIS) qualitative method, with the inclusion of additional clean-up and quantification at lower levels, which proved more efficient. Extraction was performed using a phosphate buffer containing trifluoroacetic acid followed by neutralization, purification on a cationic exchange SPE cartridge, with elution with methanol/acetic acid, evaporation, and dilution in ion-pair solvent. The method was validated according to the criteria and requirements of the European Commission Decision 2002/657/EC, showing selectivity with no matrix interference. Linearity was established for all analytes using the method of weighted minimum squares. CCalpha and CCbeta varied between 1036 and 12,293 ug kg(-1), and between 1073 and 14,588 ug kg(-1), respectively. The limits of quantification varied between 27 and 688 ug kg(-1). The values of recovery for all analytes in poultry kidney, fortified in the range of 500-1500 ug kg(-1), were higher than 90%, and the relative standard deviations were lower than 15%, except spectinomycin (21.8%). Uncertainty was estimated using a simplified methodology of 'bottom-up' and 'top-down' strategies. The results showed that this method is effective for the quantification and confirmation of aminoglycoside residues and could be used by the Brazilian programme of residue control. PMID- 22059624 TI - Coordination-driven inversion of handedness in ligand-modified PNA. AB - Peptide nucleic acid (PNA) is a synthetic analogue of DNA, which has the same nucleobases as DNA but typically has a backbone based on aminoethyl glycine (Aeg). PNA forms duplexes by Watson Crick hybridization. The Aeg-based PNA duplexes adopt a chiral helical structure but do not have a preferred handedness because they do not contain a chiral center. An L-lysine situated at the C-end of one or both strands of a PNA duplex causes the duplex to preferably adopt a left handed structure. We have introduced into the PNA duplexes both a C-terminal L lysine and one or two PNA monomers that have a gamma-(S)-methyl-aminoethyl glycine backbone, which is known to induce a preference for a right-handed structure. Indeed, we found that in these duplexes the gamma-methyl monomer exerts the dominant chiral induction effect causing the duplexes to adopt a right handed structure. The chiral PNA monomer had a 2,2':6',2''-terpyridine (Tpy) ligand instead of a nucleobase and PNA duplexes that contained one or two Tpys formed [Cu(Tpy)(2)](2+) complexes in the presence of Cu(2+). The CD spectroscopy studies showed that these metal-coordinated duplexes were right-handed due to the chiral induction effect exerted by the S-Tpy PNA monomer(s) except for the cases when the [Cu(Tpy)(2)](2+) complex was formed with Tpy ligands from two different PNA duplexes. In the latter case, the metal complex bridged the two PNA duplexes and the duplexes were left-handed. The results of this study show that the preferred handedness of a ligand-modified PNA can be switched as a consequence of metal coordination to the ligand. This finding could be used as a tool in the design of functional nucleic-acid based nanostructures. PMID- 22059625 TI - Working memory and two-digit number processing. AB - The processing of two-digit numbers in comparison tasks involves the activation and manipulation of magnitude information to decide which number is larger. The present study explored the role of different working memory (WM) components and skills in the processing of two-digit numbers by examining the unit-decade compatibility effect with Arabic digits and number words. In the study, the unit decade compatibility effect and different WM components were evaluated. The results indicated that the unit-decade compatibility effect was associated to specific WM skills depending on the number format (Arabic digits and number words). We discussed the implications of these results for the decomposed view of two-digit numbers. PMID- 22059626 TI - The stability of some intermediate moisture smoked meats during storage at 30 degrees C and 38 degrees C. AB - Intermediate moisture smoked beef was prepared by cook/soak equilibration in solution, with or without glycerol followed by smoking for 4 h or 18 h at 50 degrees C. During storage for 12 weeks at 30 and 38 degrees C all reactions except the change in pH were significatlyy slower at 30 degrees C. This suggests that certain reactions; namely, hydroxyproline solubilization and protein crosslinking, have different temperature dependencies and opposing effects on pH. Heavy smoking and glycerol both reduce the rate of protein crosslinking, as measured by solubility in 3% sodium dodecyl sulphate + 1% beta-mercaptoethanol. Glycerol accelerates hydroxyproline breakdown but helps retain moisture, available lysine and tenderness. Heavy (18 h) smoking had a reverse effect on these reactions. Browning occurs in these products, as well as rapid pigment loss. PMID- 22059627 TI - On the water condition in pork meat. AB - The water condition of cured and uncured pork, having different ageing times, was studied in the process of heating to 80 degrees C, using nuclear-magnetic resonance methods. In the transverse magnetization decay functions five components could be distinguished, differing from each other by their relative weights and relaxation times. The greatest relative weight (60-70%) was characteristic of the component having relaxation time 35-45 ms ('d'), which could be related to immobilized water. The change of the component's 'd' relative weight while heating was significantly dependent on the ageing time of meat and the factor of curing or not curing before heating. It was shown that the greatest amount of immobilized water and its strongest bonding were observed in uncured pork during the first 6-7 h and after 48 h post mortem. Cured meat possesses the highest amount of immobilized water at room temperature after 48-96 h post mortem, however, its bonding at heating is higher in the case of meat which is cured during the first hours and after 96 h post mortem. PMID- 22059628 TI - Volatile compounds of dry hams from Iberian pigs. AB - A study on volatile compounds from three batches of dry hams from Iberian pigs ('montanera', fed on acorns and pasture; 'recebo', fed on acorns, pasture and a commercial diet; and 'pienso', fed on a commercial diet) has been made. Over 64 compounds were identified in the headspace volatiles from all three batches, including aldehydes, alcohols, short-chain fatty acids, furan derivatives, lactones and other miscellaneous compounds. Significant differences were found between batches at several levels (P<0.0005, P<0.005, P<0.05) for many volatile compounds, mainly between 'montanera' and 'pienso' batches. Overall quantitative differences, but not qualitative ones, were observed between batches. PMID- 22059629 TI - Storage and display characteristics of electrically stimulated, hot-boned and nonstimulated, cold-boned beef. AB - One side, randomly selected from each of 33 carcasses from forage-fed steers, was electrically stimulated within 30 min of exsanguination and hot-bonded (ESHB). Opposite sides were not electrically stimulated and were cold-boned (NESCB) following a 24 h chill (0 degrees C). From 17 ESHB sides, portions of the longissimus dorsi (LD) and semimembranosus (SM) muscles were removed and immediately vacuum packaged. LD and SM muscles were removed from the remaining 16 ESHB sides, wrapped in polyvinyl chloride film, chilled (0 degrees C) for 22 h and then vacuum packaged. LD and SM muscles from NESCB sides (n = 33) were removed and the vacuum packed at 24 h post mortem. Whole muscle characteristics were evaluated initially and after storage periods of 7, 14 or 21 days and steaks were displayesd for 5 years thereafter. Neither hot versus cold-boning nor storage for 21 days affected retail display characteristics of LD and SM steaks (P > 0.05). As retail display time increased, retail lean color, fat color and overall appearance scores decreased. PMID- 22059630 TI - Effect of time between adrenaline injection and slaughter on the rate and extent of post-mortem metabolism in porcine skeletal muscle. AB - The aim of this work was to study the effect of time between adrenaline injection and slaughter on the rate and extent of post-mortem metabolism in pig muscle. Five pigs were subcutaneously injected with adrenaline (0.3 mg/kg) or with a saline solution 4 h, 1 h or 15 min prior to slaughter. pH(1), pH(u) and FOP(u) were measured in Longissimus dorsi (LD) and Biceps femoris (BF) muscles. m.LD samples were taken 20 days before slaughter using biopsy sampling, immediately after bleeding and 45 min post mortem for biochemical analysis. m.LD glycolytic potential (very close to glycogen content) was decreased by the injection of adrenaline 4 h and 1 h prior to slaughter, when comparing values at rest (20 days before slaughter) and values determined immediately after bleeding. The depletion was greater fro the injection performed 4 h before slaughter. In this group pH(u) was higher foe adrenaline-injected pigs (5.69 versus 5.47 for pigs injected with saline solution) but the difference was not significant. Pigs injected with adrenaline 1 h prior to slaughter exhibited higher glucose, glucose-6-phosphate and lactate levels immediately after slaughter, lower pH(1) and higher FOP values in m.LD than control pigs. Since the differences in pH(1) were not explained by differences in the rate of build-up of lactate, it was hypothesized that pigs injected with adrenaline 1 h prior to slaughter had lower muscle pH at slaughter. It was concluded that the rate or the extent of post mortem metabolism in pig muscle may be affected independently, by manipulating the time between adrenaline injection and slaughter. PMID- 22059631 TI - Relationship between myosin denaturation and the colour of low-voltage electrically-stimulated beef. AB - The semimembranosus muscles of low-voltage-electrically-stimulated beef carcases when subjected to relatively slow chill-freeze cooling were found to be significantly lighter (paler) than the equivalent muscles from unstimulated controls subjected to the same chilling procedure. There was a significant correlation (r > 0.75) between the lightness as measured by the Hunter 'L' values and the degree of denaturation of the myosin as estimated by differential scanning calorimetry. Hot or cold boning did not have a significant effect on the observed effects. In a further experiment, in which hot-boned meat was subjected to very rapid chilling and freezing, no difference in either colour or extent of myosin denaturation between stimulated and unstimulated samples was seen. However, cold-boned, slow chilled, stimulated samples were still measurably paler than the unstimulated controls. It is concluded that exposure of myosin to relatively high temperatures and pH values of 6 or less induces some unfolding of myosin which probably contributes to the observed 'paleness' of these samples. However, other factors may also contribute to the observed paleness. PMID- 22059632 TI - Effect of electrical stunning or sticking without stunning on the microstructure of zousoon, a Chinese semi-dry pork product. AB - The microstructure of muscle fibers from pigs killed following electrical stunning was compared to that from pigs killed after tying-resting and sticking. Examination of the muscle fibers demonstrated that electrical stunning resulted in contracture bands that caused tearing and fragmentation of the myofibers/myofibrils. On the other hand, tying-resting and sticking was not accompanied by microstructural fragmentation of the muscle fibers. Results indicate that electrical stunning of hogs causes fragmentation and breakage of the muscle fibers so that the meat is not suitable for production of Zousoon-a semi-dry shredded Chinese pork product and other similar items prepared from prerigor pig muscle. Heating and drying intensify the deteachment of the myofibrils from the muscle fiber bundles, which is caused mainly by electrical stunning or stimulation and improper conditioning following slaughter. The combined effects of electrical stunning and heating-drying appear to be responsible for the fragmentation of the muscle fibers/myofibrils and contribute to the unsuitability of prerigor muscle from electrically stunned pigs for use in the production of Zousoon. Since sticking of pigs without stunning does not meet humane slaughter standards, alternative animal welfare slaughter procedures should be examined from the standpoint of their usefulness in producing Zousoon. PMID- 22059633 TI - Carcass composition and meat quality of brush-tail possums (Trichosurus vulpecula). AB - One-hundred-and-thirty-nine possums, balanced as far as possible for sex (68 male, 71 female) and age (1 year, 42; 2-4 years, 61; 5+ years, 36), were slaughtered and the dissected carcass composition, muscle, and cooked meat composition measured. Possums were slaughtered at time in captivity TIC 0 (n = 58), TIC 14 days (n = 20) and TIC 28 days (n = 61). Compared with the 5+ years (mature) age group the 1 year olds (juveniles) were 67% and the 2-4 year olds (immature) 96% of the live weight of the mature possums. Carcass composition was characterised by high lean (78-80%) and low fat (around 1-2%). The cooked meat from possums is very high in protein (~ 25%) and low in fat, suggesting it should be a valuable source of animal protein with a low total fat, high unsaturated fat content. In all cases cooked meat was rated as tender, based on shear force values, despite having a pH of around 6.3. PMID- 22059634 TI - Evaluation of invasive instruments for assessment of veal colour at time of classification. AB - In a random selection of 480 veal carcasses, invasive measurements were made on the longissimus lumborum (LL) and biceps femoris (BF) with the Colormet, Hennessy Grading Probe (HGP4; LL only) and Invasive Meat Colour Meter. Surface colour of the rectus abdominis (RA) was determined instrumentally with the Minolta Chromameter and Surface Meat Colour Meter and visually by two persons, using a colour standard. All measurements were made at 30-40 min post mortem. Of the measurements made on the RA, the Surface Meat Colour Meter was best related to both visual judgements (r = -0.79; -0.73). The correlation coefficient between both visual judgements was 0.77. Clear differences were found between the invasive instruments in their ability to determine veal colour. The correlation coefficients between the invasive measurements and both visual judgements varied for the Colormet L (*)-value from -0.18 to -0.35, for the HGP4 from -0.40 to 0.49, and for the Invasive Meat Colour Meter from -0.69 to -0.74. Both for LL and BF the best relationships were found between the Invasive Meat Colour Meter and the Surface Meat Colour Meter (RA). PMID- 22059635 TI - Pigment oxidation in ground veal: Influence of lipid oxidation, iron and zinc. AB - The color stability of fresh ground veal from four different muscles (biceps femoris, longissimus dorsi, psoas major and supraspinatus) was characterized, and the effects of lipid oxidation, iron and zinc on this degradative process were investigated. Samples were minced and prepared in a manner consistent with retail production and analyzed for pH, myoglobin concentration, total and nonheme iron, and zinc. Pigment and lipid oxidation were measured on days 0, 3 and 6 of 4 degrees C storage. B. femoris demonstrated the greatest extent of lipid oxidation, and was more color-labile than p. major or supraspinatus (P < 0.05), but no different from l. dorsi (P > 0.05). Total iron and myoglobin concentrations were lowest for l. dorsi (P<0.05). Zinc concentration in the four muscles followed the order supraspinatus ? b. femoris ? l. dorsi ? p. major (P < 0.05). Data analysis revealed that initial metmyoglobin formation (days 0 to 3) was significantly correlated with total iron (r = 0.69) or nonheme iron (r = 0.68) in b. femoris, but not any of the other muscles. Correlations between lipid and pigment oxidation in each of the four muscles were performed and the data support a strong relationship between these degradative processes in ground veal. PMID- 22059637 TI - NF-kappaB activity in perinatal brain during infectious and hypoxic-ischemic insults revealed by a reporter mouse. AB - Infants suffering from infection or hypoxia-ischemia around the time of birth can develop brain damage resulting in life-long impairment such as cerebral palsy, epilepsy and cognitive disability. Inflammation appears to be an important contributor irrespective of whether the primary event is infection or hypoxia ischemia. Activation of the transcription factor NF-kappaB is a hallmark of inflammation. To study perinatal brain inflammation, we developed a transgenic reporter mouse for imaging NF-kappaB activity in live animals and tissue samples. The reporter genes firefly luciferase and a destabilized version of enhanced GFP (dEGFP) were regulated by common NF-kappaB sites using a bidirectional promoter. Luciferase activity was imaged in vivo, while dEGFP was detected at cellular level in tissue sections. In newborn mice subjected to experimental models of infections or hypoxia-ischemia; luciferase signal increased in brains of live animals. In brain sections dEGFP expression, revealing NF-kappaB activation was observed in the endothelial cells of the blood-brain barrier in all disease models. In meningitis and hypoxia-ischemia expression of dEGFP was also induced in perivascular astrocytes. In conclusion, by using this transgenic reporter mouse in experimental models of perinatal complications, we could assess NF kappaB activity in vivo and subsequently determine the cellular origin in the tissues. PMID- 22059638 TI - Does the crowded cell-like environment reduce the chaperone-like activity of alpha-crystallin? AB - The effect of crowding on the chaperone-like activity of alpha-crystallin has been studied using aggregation of UV-irradiated glycogen phosphorylase b (Phb) from rabbit skeletal muscle as an aggregation test system. The merit of this test system is the possibility of testing agents that directly affect the stage of aggregation of the protein molecules. It was shown that the solution of Phb denatured by UV contained aggregates with a hydrodynamic radius of 10.4 nm. These aggregates are relatively stable at 20 degrees C; however, they reveal a tendency to stick further in the presence of crowding agents. The study of the effect of alpha-crystallin on the aggregation of UV-irradiated Phb in the presence of the crowding agents by dynamic light scattering at 37 degrees C showed that under crowding conditions the antiaggregation ability of alpha crystallin was weakened. On the basis of the analytical ultracentrifugation, size exclusion chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis data, the scheme of interaction of UV-irradiated Phb and alpha crystallin has been proposed. It is assumed that chaperone-target protein complexes of two types are formed, namely, the complexes of dissociated forms of alpha-crystallin with a protein substrate and high-mass alpha-crystallin denatured protein complexes. The complexes of the first type reveal a weak propensity to aggregate even under crowding conditions. The complexes of the second type are characterized by the lower rate of aggregation in comparison with that of original UV-irradiated Phb. However, crowding stimulates the rate of aggregation of these complexes, resulting in the above-mentioned decrease in the chaperone-like activity of alpha-crystallin. PMID- 22059639 TI - A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD. AB - Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction >= 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation. PMID- 22059640 TI - Operating room team members' views of workload, case difficulty, and nonroutine events. AB - Interventions such as mandatory "time-outs" have contributed to intraoperative safety but improvements are still necessary. We present data provided by 3 professions always present in the intraoperative setting that suggest next steps in the quest for improvements. We describe the differences and similarities in operating room (OR) nurses', anesthesia providers', and surgeons' beliefs about team function, case difficulty, nonroutine event (NRE), and error causation using a qualitative design at 3 Veterans' Administration hospitals. Intraoperative errors are costly in lives, suffering, and dollars. A quality improvement tenet states that workers are a rich information source regarding the context within which quality can be improved. Identifying and describing OR providers' beliefs are necessary steps in devising novel approaches to quality improvement. Intraoperative NRE and error prevention opportunities exist within and outside of the OR. There may be "cascade" and "perfect storm conditions" before and during operative procedures that increase the likelihood of NREs. Confirmation of these phenomena could improve prediction and prevention of NREs. Exploration of differences in team definition and team performance ratings by provider type may also identify avenues for improvement. PMID- 22059641 TI - Prebiotic significance of extraterrestrial ice photochemistry: detection of hydantoin in organic residues. AB - The delivery of extraterrestrial organic materials to primitive Earth from meteorites or micrometeorites has long been postulated to be one of the origins of the prebiotic molecules involved in the subsequent apparition of life. Here, we report on experiments in which vacuum UV photo-irradiation of interstellar/circumstellar ice analogues containing H(2)O, CH(3)OH, and NH(3) led to the production of several molecules of prebiotic interest. These were recovered at room temperature in the semi-refractory, water-soluble residues after evaporation of the ice. In particular, we detected small quantities of hydantoin (2,4-imidazolidinedione), a species suspected to play an important role in the formation of poly- and oligopeptides. In addition, hydantoin is known to form under extraterrestrial, abiotic conditions, since it has been detected, along with various other derivatives, in the soluble part of organic matter of primitive carbonaceous meteorites. This result, together with other related experiments reported recently, points to the potential importance of the photochemistry of interstellar "dirty" ices in the formation of organics in Solar System materials. Such molecules could then have been delivered to the surface of primitive Earth, as well as other telluric (exo-) planets, to help trigger first prebiotic reactions with the capacity to lead to some form of primitive biomolecular activity. PMID- 22059642 TI - Comparison of the roles of nucleotide synthesis, polymerization, and recombination in the origin of autocatalytic sets of RNAs. AB - Ribozymes that act as polymerases and nucleotide synthases are known experimentally, even though no fully self-replicating system has yet been found. If the RNA World hypothesis is true, ribozymes must have arisen initially from within a random abiotic polymerization system. To investigate the origin of the RNA world, we studied a mathematical model of a chemical reaction system describing RNA polymerization. It is supposed that, in absence of ribozymes, polymerization occurs at a small spontaneous rate, and that in the presence of polymerase ribozymes, polymerization occurs at a faster rate that is proportional to the ribozyme concentration. Chains must be longer than a minimum threshold length in order to have the possibility of acting as ribozymes. The reaction system has two stable states that we term dead and living. The dead state is controlled by the small spontaneous rate and has negligible concentration of ribozymes. The living state has high concentration of ribozymes, and the reaction rates are determined by the ribozymes; thus, the system is autocatalytic. Concentration fluctuations in a finite volume can cause a transition to occur from the dead to the living state, that is, an origin of life occurs within this model. We also consider ribozymes that catalyze nucleotide synthesis. We show that living and dead states arise in the presence of synthase ribozymes in the same way as for polymerases. It has been proposed that recombination reactions are a way of generating long RNA chains in the early stages of life. We show that if the possibility of random reversible recombination reactions is added to our model, this does not lead to an increase in long polymer concentration. Thus, if recombination is fully reversible, there is no autocatalytic state controlled by recombination. Nevertheless, recombination can play an important role in ribozyme synthesis if there is an additional process that keeps the recombination reactions out of equilibrium. We modeled a case studied experimentally in which building block strands of moderate length associate due to RNA secondary structure formation. A recombination reaction then occurs between these strands to form a longer sequence that catalyzes its own formation via the recombination reaction. This system has an autocatalytic state, and it is possible for it to arise within our random polymerization system. If complexes formed by associations of shorter strands can act as catalysts without the requirement that the strands be covalently linked, this would alleviate the need for synthesis of very long strands; hence, it makes the emergence of an autocatalytic system from an abiotic random polymerization system much more likely. PMID- 22059643 TI - Mucopolysaccharidosis type II: European recommendations for the diagnosis and multidisciplinary management of a rare disease. AB - Mucopolysaccharidosis type II (MPS II) is a rare, life-limiting, X-linked recessive disease characterised by deficiency of the lysosomal enzyme iduronate-2 sulfatase. Consequent accumulation of glycosaminoglycans leads to pathological changes in multiple body systems. Age at onset, signs and symptoms, and disease progression are heterogeneous, and patients may present with many different manifestations to a wide range of specialists. Expertise in diagnosing and managing MPS II varies widely between countries, and substantial delays between disease onset and diagnosis can occur. In recent years, disease-specific treatments such as enzyme replacement therapy and stem cell transplantation have helped to address the underlying enzyme deficiency in patients with MPS II. However, the multisystem nature of this disorder and the irreversibility of some manifestations mean that most patients require substantial medical support from many different specialists, even if they are receiving treatment. This article presents an overview of how to recognise, diagnose, and care for patients with MPS II. Particular focus is given to the multidisciplinary nature of patient management, which requires input from paediatricians, specialist nurses, otorhinolaryngologists, orthopaedic surgeons, ophthalmologists, cardiologists, pneumologists, anaesthesiologists, neurologists, physiotherapists, occupational therapists, speech therapists, psychologists, social workers, homecare companies and patient societies. TAKE-HOME MESSAGE: Expertise in recognising and treating patients with MPS II varies widely between countries. This article presents pan European recommendations for the diagnosis and management of this life-limiting disease. PMID- 22059644 TI - Effects of acute ingestion of different fats on oxidative stress and inflammation in overweight and obese adults. AB - BACKGROUND: Studies show that obese individuals have prolonged elevations in postprandial lipemia and an exacerbated inflammatory response to high fat meals, which can increase risk for cardiovascular diseases. As epidemiological studies indicate an association between type of fat and circulating inflammatory markers, the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals. METHODS: Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat (MFA), saturated fat (SFA), or long-chain omega 3 polyunsaturated fat (O3FA) in random order. Blood samples collected at baseline, 1, 2, 4, and 6 hours postprandial were analyzed for markers of inflammation (soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor- alpha (TNF-alpha), and C-reactive protein (CRP)), oxidative stress (8-epi-prostaglandin-F2alpha (8-epi) and nuclear factor-kappaB (NF-kappaB)), and metabolic factors (glucose, insulin, non esterified free fatty acids, and triglycerides (TG)). RESULTS: O3FA enhanced NF kB activation compared to SFA, but did not increase any inflammatory factors measured. Conversely, SFA led to higher ICAM-1 levels than MFA (p = 0.051), while MFA increased TG more than SFA (p < 0.05). CRP increased while TNF-alpha and 8 epi decreased with no difference between treatments. CONCLUSIONS: While most of the inflammatory factors measured had modest or no change following the meal, ICAM-1 and NF-kappaB responded differently by meal type. These results are provocative and suggest that type of fat in meals may differentially influence postprandial inflammation and endothelial activation. PMID- 22059645 TI - Mass-dependent bond vibrational dynamics influence catalysis by HIV-1 protease. AB - Protein motions that occur on the microsecond to millisecond time scale have been linked to enzymatic rates observed for catalytic turnovers, but not to transition state barrier crossing. It has been hypothesized that enzyme motions on the femtosecond time scale of bond vibrations play a role in transition state formation. Here, we perturb femtosecond motion by substituting all nonexchangeable carbon, nitrogen, and hydrogen atoms with (13)C, (15)N, and (2)H and observe the catalytic effects in HIV-1 protease. According to the Born Oppenheimer approximation, isotopic substitution alters vibrational frequency with unchanged electrostatic properties. With the use of a fluorescent peptide to report on multiple steps in the reaction, we observe significantly reduced rates in the heavy enzyme relative to the light enzyme. A possible interpretation of our results is that there exists a dynamic link between mass-dependent bond vibrations of the enzyme and events in the reaction coordinate. PMID- 22059646 TI - Severe ranitidine-induced anaphylaxis: a case report and literature review. AB - WHAT IS KNOWN AND OBJECTIVE: Ranitidine is a generally well-tolerated drug, and serious side effects are rare. However, ranitidine-induced anaphylaxis has been reported on rare occasions. We report on such a case and review other cases reported in the literature. CASE SUMMARY: A 36-year-old man with no history of other medications, illnesses or allergic diseases, especially to drugs, consulted our emergency department because of renal colic and epigastric discomfort. He was given 50 mg of ranitidine as a slow intravenous bolus and 20 mg of piroxicam intramuscularly. Within the first minute, the patient developed a cold sweat, trembling, dyspnoea and deterioration of his consciousness. The condition was considered as an anaphylactic shock, and cardiopulmonary resuscitation and inotropic support were immediately commenced. Two days later, he was weaned off the ventilator as he was haemodynamically stable. He was discharged after 7 days. Four weeks later, skin prick tests to ranitidine and piroxicam were performed on the forearm of the patient. He reacted strongly to ranitidine about 10 min later but not to piroxicam. To assess cross-reactivity to other H2- and H1-receptor antagonists in our patient, we subsequently performed prick tests to famotidine, cimetidine and desloratadine and all were negative. WHAT IS NEW AND CONCLUSION: We re-emphasize a potentially serious, albeit very rare, adverse effect of ranitidine and summarize other reported cases. This case demonstrates that commonly used, generally safe drugs may on occasions cause serious adverse effects. PMID- 22059647 TI - Pharmacokinetic evaluation of roflumilast. AB - INTRODUCTION: Roflumilast is a selective PDE4 inhibitor recently approved for oral, once-daily treatment of severe chronic obstructive pulmonary disease (COPD). Clinical trials have demonstrated the effect of roflumilast on reducing exacerbation frequency and improving lung function in COPD, while its mode of action may offer the potential to target the inflammatory processes underlying COPD. Roflumilast is, therefore, an important addition to current therapeutic options. It is catalyzed by cytochrome P450 (CYP) 1A2 and 3A4 to its active metabolite, roflumilast N-oxide, which accounts for > 90% of roflumilast total PDE4 inhibitory activity. AREAS COVERED: This article reviews the pharmacokinetics of roflumilast and considers the effects of co-administration with CYP inhibitors or inducers, and other medications commonly used in patients with COPD, on the pharmacokinetics of roflumilast and roflumilast N-oxide. EXPERT OPINION: Roflumilast has novel anti-inflammatory activity in COPD that provides the physician with a treatment option beyond bronchodilation. It can be co administered with many medications commonly used by patients with COPD and its anti-inflammatory activity provides incremental benefits on top of existing therapies. Future research will further elucidate the impact of roflumilast on COPD and beyond, while alternative dosing regimens may offer a means to ameliorate transient tolerability issues. PMID- 22059648 TI - Synthesis and properties of a bridged nucleic acid with a perhydro-1,2-oxazin-3 one ring. AB - A novel derivative of 2',4'-bridged nucleic acid, named hydroxamate-bridged nucleic acid (HxNA), containing a six-membered perhydro-1,2-oxazin-3-one ring, was designed and synthesized. The introduction of a carbonyl function along with an N-O linkage in the six-membered bridged structure is the unique structural feature of the novel 2',4'-bridged nucleic acid analogue. The design was carried out to restrict the flexibility of the sugar moiety through the trigonal planarity of carbonyl function, which would improve the properties of the modification. The synthesized monomer was incorporated into oligonucleotides, and their properties were examined. The HxNA-modified oligonucleotides exhibited selectively high affinity toward complementary ssRNA. Furthermore, the nuclease resistance of the HxNA-modified oligonucleotide was found to be higher than that of the corresponding natural and 2',4'-BNA/LNA-modified oligonucleotides. Interestingly, exposure of HxNA modified oligonucleotide to 3'-exonuclease resulted in gradual opening of the bridge, which stopped further digestion. Moreover, ring-opening of only one modification at the 3'-end of the oligonucleotides was observed, even if two or three HxNA modifications were present in the sequence. The results demonstrate the strong potential of the HxNA modification as a switch for the generation of highly nuclease-resistant RNA selective oligonucleotide in situ, which could have potential applications in antisense technology. PMID- 22059649 TI - Dual task performance of working memory and postural control in major depressive disorder. AB - OBJECTIVE: Previous studies with patients diagnosed with Major Depressive Disorder (MDD) revealed deficits in working memory and executive functions. In the present study we investigated whether patients with MDD have the ability to allocate cognitive resources in dual task performance of a highly challenging cognitive task (working memory) and a task that is seemingly automatic in nature (postural control). METHOD: Fifteen young (18-35 years old) patients with MDD and 24 healthy age-matched controls performed a working memory task and two postural control tasks (standing on a stable or on a moving platform) both separately (single task) and concurrently (dual task). RESULTS: Postural stability under single task conditions was similar in the two groups, and in line with earlier studies, MDD patients recalled fewer working memory items than controls. To equate working memory challenges for patients and controls, task difficulty (number of items presented) in dual task was individually adjusted such that accuracy of working memory performance was similar for the two groups under single task conditions. Patients showed greater postural instability in dual task performance on the stable platform, and more importantly when posture task difficulty increased (moving platform) they showed deficits in both working memory accuracy and postural stability compared with healthy controls. CONCLUSIONS: We interpret our results as evidence for executive control deficits in MDD patients that affect their task coordination. In multitasking, these deficits affect not only cognitive but also sensorimotor task performance. PMID- 22059651 TI - Progression rate of newly diagnosed impaired fasting glycemia to type 2 diabetes mellitus: a study using the National Healthcare Group Diabetes Registry in Singapore. AB - BACKGROUND: The aims of the present study were to estimate the rate of progression from newly diagnosed impaired fasting glycemia (IFG) to type 2 diabetes mellitus (T2DM) in Singapore and to identify factors associated with the progression to T2DM in individuals with newly diagnosed IFG. METHODS: The present study was a retrospective cohort study of newly diagnosed IFG from the National Healthcare Group Diabetes Registry between 1 January 2006 and 31 December 2007 to estimated the rate of progression to T2DM. Univariate survival analysis, followed by multivariate survival analysis, was performed and interactions were tested in the final model. RESULTS: Over a mean follow-up period of 1.65 +/- 0.13 years, 85 of 490 participants with newly diagnosed IFG developed T2DM, giving an annual progression rate of 6.8%. The factors associated with the development of T2DM were higher fasting plasma glucose level in the year of IFG diagnosis (hazard ratio [HR] = 14.6; 95% confidence interval [CI] 5.66-37.5), Chinese race (HR = 2.70; 95% CI 1.44-5.06), and body mass index (HR = 1.11; 95% CI, 1.06-1.15). CONCLUSIONS: The progression rate to T2DM is high in subjects with newly diagnosed IFG. Intensive lifestyle modification can be incorporated into their current yearly follow-up to prevent progression to T2DM, which is a growing problem in Singapore. PMID- 22059650 TI - Deconstructing spatial working memory and attention deficits in multiple sclerosis. AB - OBJECTIVE: To investigate whether spatial working memory (WM) is impaired in multiple sclerosis (MS), and, if it is, to localize impairment to specific cognitive subprocess(es). METHOD: In Experiment 1, MS and control participants performed computerized memory-span and visuomotor tasks. WM subprocesses were taxed by manipulating (1) the requirement to remember serial order, (2) delay duration, and (3) the presence of irrelevant stimuli during target presentation. In Experiment 2, recall and recognition tests varied the difficulty of WM retrieval. In Experiment 3, an attention-cueing task tested the ability to voluntarily and rapidly reorient attention. RESULTS: Performance was worse for MS than for control participants in both spatial recall (Exp. 1 span: 95% CIMS = [5.11, 5.57], 95% CIControls = [5.58, 6.03], p = .003, 1-tailed; Exp. 2 span: 95% CIMS = [4.44, 5.54], 95% CIControls = [5.47, 6.57], p = .006, 1-tailed) and recognition (accuracy: 95% CIMS = [0.71, 0.81], 95% CIControls = [0.79, 0.88], p = .01, 1-tailed) tests. However, there was no evidence for deficits in spatiotemporal binding, maintenance, retrieval, distractor suppression, or visuomotor processing. In contrast, MS participants were abnormally slow to reorient attention (cueing effect (ms): 95% CIMS: [90, 169], 95% CIControls: [29, 107], p = .015, 1-tailed). CONCLUSIONS: Results suggest that, whereas spatial WM is impaired in MS, once spatial information has been adequately encoded into WM, individuals with MS are, on average, able to maintain and retrieve this information. Impoverished encoding of spatial information, however, may be due to inefficient voluntary orienting of attention. PMID- 22059652 TI - Associations between low literacy and health status measures: cross-sectional analyses of two physical activity trials. AB - Arthritis researchers have thoroughly documented a powerful relationship between years of education and health outcomes, but they have not documented the role of literacy. The authors examined the associations between literacy and arthritis health status measures. Participants were recruited from southeastern urban and rural areas. Rapid Estimate of Adult Literacy in Medicine, which provides an estimate of reading level in less than 3 minutes, was administered to 447 participants at baseline in 2 community-based randomized controlled trials of lifestyle interventions designed for aging sedentary adults with arthritis. Those who read below ninth grade were considered to have low literacy. Among the 447 study participants, the median sample age was 69 years. A majority of the participants were women (86%), Caucasian (80%), overweight or obese (72%). Of all participants, 20% had low literacy. Significantly more African Americans (54%) than Caucasians (12%) had low literacy levels (p < .001). Individuals with low literacy did not have significantly worse disability or arthritis symptoms than individuals with adequate literacy (all ps > .05). Among our study participants, 1 in 5 had low literacy, but literacy was not associated with health status in this population. PMID- 22059653 TI - Ruthenium complexes of thiaporphyrin and dithiaporphyrin. AB - Successful synthesis and characterization of the six-coordinated complex [Ru(STTP)(CO)Cl] (1; STTP = 5,10,15,20-tetratolyl-21-thiaporphyrinato) allowed the development of the coordination chemistry of ruthenium-thiaporphyrin through dechlorination and metathesis reactions. Accordingly, [Ru(II)(STTP)(CO)X] (X = NO(3)(-) (2), NO(2)(-) (3), and N(3)(-) (4)) was synthesized and analyzed by single-crystal X-ray structural determination and NMR, UV-vis, and FT-IR spectroscopic methods. An independent reaction of STPPH and [Ru(COD)Cl(2)] led to [Ru(III)(STTP)Cl(2)] (5), which possessed a higher-valent Ru(III) center and exhibited good stability in the solution state. This stability allowed reversible redox processes in a cyclic voltammetric study. Reactions of [Ru(S(2)TTP)Cl(2)] (S(2)TTP = 5,10,15,20-tetratolyl-21,23-dithiaporphyrinato) with AgNO(3) and NaSePh, also via the metathesis strategy, resulted in novel dithiaporphyrin complexes [Ru(II)(S(2)TTP)(NO(3))(2)] (6) and [Ru(0)(S(2)TTP)(PhSeCH(2)SePh)(2)] (7), respectively. The structures of 6 and 7 were corroborated by X-ray crystallographic analyses. Complex 7 is an unprecedented ruthenium(0) dithiaporphyrin with two bis(phenylseleno)methanes as axial ligands. A comparison of the analyses of the crude products from reactions of NaSePh and CH(2)Cl(2) with or without [Ru(S(2)TTP)Cl(2)], further supported by UV-vis spectral changes under stoichiometric reactions between [Ru(S(2)TTP)Cl(2)] and NaSePh, suggested a reaction sequence in the order of (1) formation of a putative [Ru(II)(S(2)TTP)(SePh)(2)] intermediate, followed by (2) the concerted formation of PhSe-CH(2)Cl and simultaneously a reduction of Ru(II) to Ru(0) and finally (3) nucleophilic substitution of PhSeCH(2)Cl by excess PhSe(-), resulting in PhSeCH(2)SePh, which readily coordinated to the Ru(0) and completed the formation of bis(phenylseleno)methane complex 7. PMID- 22059654 TI - Microbiological examination of pre-storage and post-storage intervention beef. AB - Intervention processing involves processing techniques substantially different from traditional carcass dressing operations. Microbiological analysis of the bacterial flora of intervention beef found that this product had a bacterial population which was similar to that typically encountered on chill stored carcass beef. Counts obtained from freshly processed boned out forequarters displayed mean log(10) counts in the range 3.62-5.37 per gram dependent on enumeration conditions. Post-storage counts were of similar magnitudes. Pre- and post-storage samples demonstrated great genus diversity. Genera diversity was preserved throughout frozen storage yielding a product contaminated with pathogen containing genera in sizeable proportions. Reasons for the broad similarity in microbial loading, despite numerous divergencies from standard slaughter techniques, between intervention beef and aerobically chill stored beef are discussed. PMID- 22059655 TI - Quality of fresh retail pork cuts stored in modified atmosphere under temperature conditions simulating export to distant markets. AB - The effect of storage temperature on microbial and sensory quality of retail cuts of pork was determined on samples stored under temperature regimens designed to simulate conditions that could be encountered in accessing distant markets with retail-ready product. Samples were packaged in modified atmosphere with 100% CO(2) and <200 ppm O(2) in plastic film with extremely low gas transmission rates. All samples were stored at -1.5 degrees C for three weeks. Reference samples were held at -1.5 degrees C for the duration of the study; experimental samples were transferred to 4 degrees C (-1.5 4 degrees C ) or 7 degrees C (-1. 517 degrees C ) and analyzed for microbial content and sebsory attributes including appearance, confinement and meat odours. Storage life of reference samples at -1.5 degrees C was seven weeks before rejection for loss of acceptable appearance. With transfer of samples to 4 and 7 degrees C after three weeks at 1.5 degrees C, samples remained acceptable for retail sale for two weeks and one week, restpectively. The microbial flora was dominated by lactic acid bacteria under all three storage conditions. Appearance of the cuts was the principal criterion limiting storage life. Discoloration of the meat was not a problem in this study, but purge and odour, including sour and sulphur notes, became a problem with time. The study indicated that export of retail-ready pork cuts to distant markets with a three-week time for delivery to market at -1.5 degrees C can be achieved with one to two weeks of marketing time at retail market at 4 to 7 degrees C. PMID- 22059656 TI - Effect of temperature on porcine-muscle metabolism studied in isolated muscle fibre strips. AB - In the period before and after slaughter, muscle temperature differs between pigs, which is likely to influence muscle metabolism. Muscle-fibre strips were isolated under anaesthesia from six halothane-negative Large White pigs and eight halothane-positive Pietrain pigs and kept in oxygenated Krebs medium at 38, 40, or 42 degrees C, to study the effects of temperature on muscle metabolism. During a period of oxygenation, contraction measurements were carried out to assess the physiological state of the muscle-fibre strips. Aerated Krebs solution was replaced by paraffin oil at the same temperature to simulate post-mortem muscle metabolism. Pietrain muscle-fibre strips were more affected by preparation methods than Large White muscle strips, which led to a higher metabolite breakdown at the time of cessation of the oxygen supply. Pietrain muscle-fibre strips also showed a larger decrease in twitch-force contraction during the period of oxygenation. A moderate effect of temperature on energy metabolism could be seen in muscle-fibre strips of both types of pig, with increasing post mortem metabolite breakdown at higher temperatures. However, this effect can play only a limited role in the tremendous acceleration of the post-mortem pH fall as observed in PSE muscle (up to five to ten times the normal rate). PMID- 22059657 TI - Is colour brightness (L-value) a reliable indicator of water-holding capacity in porcine muscle? AB - A total of 265 pork carcasses representing a broad variation in quality was used to examine the relationship between colour (L-value) and water-holding capacity (WHC) in the longissimus thoracis et lumborum. Thirty-four samples appeared to possess 'normal' reddish pink colour (L-value 52.0-58.0) but had 'unacceptable' WHC (>5.0% drip loss). Conversely, 25 samples were pale in colour (L-value >58.0) but were 'acceptable' in WHC. When muscles were dark (L-value 52.0) the WHC was always acceptable. Some samples were subjected to further analysis. Variations in iron content, haematin content, sarcomere length and degree of soluble protein denaturation failed to explain why brightness and WHC were not more closely related. When L-value and WHC were compared to pH(45) (pH, 45 min post mortem), WHC exhibited a biphasic relationship to pH(45) whereas L-value did not. These results indicate that WHC and brightness are determined by independent pre-rigor biological phenomena, strengthening the argument that brightness is not necessarily a reliable predictor of WHC. Researchers selecting pork for specific investigations, or commercial companies using fresh pork for either further processing or for retail, should not rely on colour brightness alone to insure that other quality properties such as WHC and firmness will also be acceptable. PMID- 22059658 TI - Lipolysis, proteolysis and formation of volatile components during ripening of a fermented sausage with Pediococcus pentosaceus and Staphylococcus xylosus as starter cultures. AB - Bacterial growth, formation of acids, lipolysis, proteolysis, fat oxidation, formation of volatile compounds and flavour characteristics were followed during ripening and storage of a fermented sausage. The starter culture used was composed of Pediococcus pentosaceus and Staphylococcus xylosus. The number of Pediococcus sp. increased by 1.5 log cfu/g during the first day of processing and remained constant at this level for 3 weeks. The corresponding initial increase in the numbers of Staphylococcus sp., 0.4 log cfu/g, was followed by a rapid decrease in the viable numbers. Lactic acid, mainly d-lactic acid, and acetic acid were formed during ripening. The triglycerides were hydrolysed to 1,2 diglycerides and free fatty acids at the beginning of ripening, followed by the formation of 1,3-diglycerides and monoglycerides, indicating lipolytic activity. Moreover, the nonprotein nitrogen increased during ripening as a result of the proteolytic activity. Most of the changes with respect to pH, formation of d lactic acid, acetic acid, peroxides and flavour development occurred during the initial 3 days of ripening, when growth of Pediococcus sp. and Staphylococcus sp. occurred. Lipolysis as well as proteolysis continued after this initial period. The volatile compounds identified belonged to several chemical families, viz. aliphatic and aromatic hydrocarbons, aldehydes, ketones, alcohols, phenols, carboxylic acids, esters, nitrogen compounds, sulphur compounds, chloride compounds, terpenes and furans. Many of the volatile compounds probably originated from smoke and seasoning (onion/garlic and pepper), while others were a result of the activities of muscle enzymes and bacteria. PMID- 22059659 TI - Effects of high pressure treatment on the proteolytic enzymes in meat. AB - This paper describes the effects of high-pressure treatment on proteolytic enzymes in muscle, especially catheptic enzymes which influence meat tenderization, and on acid phosphatase, used as an index of disruption of lysosomal membranes. Acid phosphatase activity in the extract from pressurized muscle increased with increasing pressure applied to the muscle up to 500 MPa. Activity of cathepsin B, D and L increased up to 400 MPa, then tended to decrease at 500 MPa. Cathepsin H and aminopeptidase B decreased with the increasing pressure. Measurements of enzymic activity in the pressurized crude extract, to investigate the pressure effect on the enzymes themselves, showed that all enzymes studied in this paper lost their enzymic activity as applied pressure increased. When the pressurized extracts were subjected to the gel-filtration chromatography, a decrease in the activities of cathepsin H and aminopeptidase B and an increase in the activities of cathepsins B and L and acid phosphatase were observed. It seems that the decrease in activity of the enzymes eluted early from the column (cathepsin H and aminopeptidase B) is due to decrease in the amount of protein eluted by the pressure treatment, whereas the increase in activity of the enzymes eluted late (cathepsin B, L and acid phosphatase) is due to an increase in the amount of protein eluted. From the results, it was concluded that the pressure-induced increase in the amount of protease activity in the muscle was due to the release of the enzymes from lysosomes. PMID- 22059660 TI - Parameters determining the quality of charqui, an intermediate moisture meat product. AB - Charqui is a typical Brazilian meat product obtained by salting and sun-drying beef samples. The chemical, physical and microbiological characteristics of the charqui were evaluated throughout processing and storage. The results confirm charqui is an intermediate moisture meat product (A(w) = 0.70-0.75). A close relationship between moisture, pretein and ash vaiues was found, suggesting the possibility of using the resulting charqui A(w) value as a parameter to define the product instead of the official moisture and mineral residue contents. The TBA determination, which expresses the state of lipid oxidation, rapidly reached the maximum value, corroborating the previous observations on the salt pro oxidant role, and then decreased gradually. A gradual decrease in microorganism count during processing and storage of charqui was also observed. These results indicate the feasibility of obtaining a final product with a low level of microbial count when raw materials of good quality, and adequate handling conditions, are used for charqui production. PMID- 22059661 TI - Predicting the weight of lean meat in lamb carcasses and the suitability of this characteristic as a basis for valuing carcasses. AB - The carcasses of 138 lambs were dissected into fat, muscle and bone as the basis for developing a model to estimate the weight of lean meat (muscle and intramuscular fat). The lambs represented two sexes (70 wethers, 68 ewes) and three sire genotypes (67 Poll Dorset, 39 Suffolk, 32 Wiltshire Horn) all from Border Leicester * Polwarth * Booroola type ewes. Hot carcass weight (HWT) was found to explain the majority of the variation in the weight of lean meat. When measures of subcutaneous fat depth at different sites were used as predictors in addition to HWT, the accuracy with which lean meat yield could be estimated was found to increase by a small amount. There was, however, little difference in their individual value as predictors. The area of the M. longissimus thoracis et lumborum at the twelfth-thirteenth rib was found to account for the significant breed type difference between Poll Dorset and Suffolk sired lambs when included in a multiple regression with HWT and the GR measurement (tissue thickness at the twelfth rib 110 mm from the midline). The final model produced an R(2) = 0.92 and an RSD = 0.45 kg for the 106 lambs. Using the model for the 106 lambs, the estimated (from the model) and actual values of lean meat for the Wiltshire Horn sired lambs were compared. The correlation coefficient between the values was r = 0.97 and the RSD was 0.31 kg. This shows that for second cross lambs as used in this study the fitted model exhibits a degree of general validity and stability. An overall model for the 138 lambs produced an R(2) = 0.92 an RSD = 0.43 kg. The potential for pricing meat on the basis of lean meat yield is discussed, with particular emphasis on the current developments in assessment of lamb carcasses in Australia. PMID- 22059662 TI - Effect of chitosan in meat preservation. AB - The effect of chitosan in meat preservation, including microbiological, chemical, sensory and color qualities, was examined. In liquid medium, chitosan (0.01%) inhibited the growth of some spoilage bacteria such as Bacillus subtilis IFO 3025, Escherichia coli RB, Pseudomonas fragi IFO 3458 and Staphylococcus aureus IAM 1011. At higher concentrations (0.1 and 1.0%) it inhibited the growth of the meat starter cultures, Lactobacillus plantarium IAM 1216, Pediococcus pentosaceus IAM 12296 and Micrococcus varians IFO 3765. In meat, during incubation at 30 degrees C for 48 h or storage at 4 degrees C for 10 days, 0.5-1.0% chitosan inhibited the growth of spoilage bacteria, reduced lipid oxidation and putrefaction, and resulted in better sensory attributes. Chitosan also had a good effect on the development of the red color of meat during storage. PMID- 22059663 TI - Effects of double-muscling on carcass quality, beef tenderness and myofibrillar protein degradation in Belgian Blue White bulls. AB - Carcass properties and meat quality characteristics of 32 Belgian Blue White double-muscled bulls (DM) were compared with those of 59 bulls of the same breed with normal conformation (N). DM showed superior carcass quality as revealed in increased dressing percentage, meat production yield, conformation grade, muscle/fat and muscle/bone ratios (all P < 0.001). Longissimus dorsi (LD) shear force values, drip and cooking losses at 8 days post mortem (pm) were significantly higher (P < 0.001) for DM, whereas sarcomere lengths were not different. Calpain 1 and calpastatin levels at 1 h and 24 h pm were tremendously decreased in DM as were also cathepsin B and L levels at 1 and 8 days pm (P < 0.001). As evident from semi-quantitative SDS-PAGE, these differences were accompanied by higher titin and lower 30 kDa levels (P < 0.001) in DM. Troponin-t levels were not different, but very low. Intramuscular collagen content was significantly lower in DM (P < 0.001). This suggests that lower background toughness in DM was compensated for by reduced post-mortem proteolytic tenderization. Discrepancy with literature reports regarding tenderness of DM might be related to the extreme muscularity of the Belgian Blue White breed, compared to other DM breeds. The results also suggest that reduced protein turnover might be involved in the muscle hypertrophy phenomenon within this breed, because of likely reduced levels of calpains and cathepsins in living DM animals. PMID- 22059664 TI - Intramuscular fat and muscle fibre lipid contents in halothane-gene-free pigs fed high or low protein diets and its relation to meat quality. AB - Immediately after exsanguination, samples were taken from M. longissimus dorsi (LD) and M. biceps fermorsi (BF) of halothane-gene-free Swedish Yorkshire pigs (entire males and gilts) fed a high-protein (18.5% crude protein, 0.96% lysine; n = 20) or a low-protein diet (13.1% crude protein, 0.64% lysine; n = 20). The lipid content, measured as triglyceride (TG), was analysed after the samples had been freeze-dried and dissected free from blood, fat and connective tissue. Fibre type composition (type I, IIA, IIB, IIC) was analysed by histochemical staining on all samples. In 14 samples of LD, representing the entire variation of the intramuscular fat content (IMF) among the 40 animals, fibre areas, lipid content and oxidative capacity within the fibre types were evaluated. IMF, meat colour and drip loss were measured in both muscles. Shear force was measured on cooked meat samples from LD. IMF was higher in both LD (2.5%) and BF (2.0%) from pigs on the low-protein diet compared with LD (1.5%) and BF (1.3%) from pigs on the high protein diet. TG content did not differ between diets in BF but was higher in LD from pigs on low- vis-a-vis high protein diet. A significant correlation was seen in LD between IMF and TG content (r = 0.57; P < 0.001). Fibre type composition did not differ between pigs on the two diets. BF had a higher proportion of type I and IIA fibres and a lower proportion of IIB fibres, compared with LD. TG content in muscle was not correlated with fibre type composition or staining intensity for lipids and oxidative capacity. High staining intensity for lipid in LD was seen in all type I fibres and in some type IIA fibres. Meat quality parameters did not differ between groups except shear force, which was higher in pigs fed the high- vis-a-vis low-protein diet (4.7 and 4.0 kg/cm(2), respectively). Shear force was correlated significantly with TG content (r = 0.42; P < 0.01) and IMF (r = -0.43; P < 0.01) in LD. The results of this study show that lipids are stored mainly in type I fibres and in some type IIA fibres. Intracellular triglycerides account for only a small fraction of IMF. The results indicate that IMF and TG content in muscle fibres may be related to shear force. PMID- 22059665 TI - Incidence of different pork quality categories in a Portuguese slaughterhouse: A survey. AB - This study was designed to evaluate the incidence of the PSE/DFD status in a Portuguese pig slaughterhouse, covering two seasons of the year (spring and summer) in order to find out if the proportions of those poor meat quality categories were sufficient to concern the meat industry. Meat quality classification was based on the measurements of the pH(60), pH(24), drip losses and colour (L, a, b) in the longissimus dorsi muscle (between the last third and fourth ribs) of 380 pigs randomly chosen from the line. The high global incidence of PSE and likely PSE (30%) as well as DFD (10%) carcasses and the enormous variation of the meat quality between the different days of analysis proves that the pig population presents a great variation of halothane genotype and that handling procedures have to be optimized in order to decrease stress and glycogen store depletion. The percentage of PSE carcasses during the summer season was double that found in the spring, probably due to a higher environmental temperature and relative humidity. PMID- 22059666 TI - Physiological aspects of androstenone and skatole formation in the boar-A review with experimental data. AB - The advantages of boars in fattening performance and carcass traits when compared with the other sexes are explained by testicular anabolic hormones. The steroid androstenone with a pronounced urine-like odour is the main objection against boar meat. More recently skatole (faecal odour) has been identified as another contributor to off-odour of pork. Androstenone is synthesized in the testes, secreted into the circulation and accumulated in adipose tissue due to its lipophilic property. Its biosynthesis is linked to the synthesis of anabolic testicular hormones. Therefore no practical method is available to maintain the sex-dependent anabolic potential of boars and to suppress androstenone selectively. Skatole is formed from tryptophan by specialized microbes in the colon when energy in the colon is limited. Gonadal hormones, but also growth hormone and IGF-1, favour its formation. Oestrogens, which are synthesized in high amounts in boar testes, decrease voluntary food intake, thus lowering the intestinal passage rate. Additionally oestrogens probably influence directly intestinal contractions via specific gut receptors. It appears, however, that glucocorticoids are more important. They counteract mitogenic hormones, such as IGF-1, ultimately leading to gut mucosal cell degradation. The resulting cell debris probably is the main source of tryptophan for microbial skatole formation. In contrast to androstenone, skatole formation can be easily suppressed by dietary means. PMID- 22059667 TI - Influence of low dose irradiation on the quality of fresh buffalo meat stored at 0-3 degrees C. AB - The effect of low dose irradiation on the microbiological, chemical and sensory qualities of fresh buffalo meat stored at 0-3 degrees C was studied. Meat slices packed in polyethylene bags subjected to 2.5 kGy dose had a shelf-life of 4 weeks with acceptable sensory score, low total volatile basic nitrogen values and remarkable improvement in microbiological quality. Irradiated meat was completely free of Pseudomonas spp. and Enterobacteriaceae throughout storage. In contrast, the unirradiated control meat spoiled within 2 weeks. PMID- 22059668 TI - Structural changes in endomysium and perimysium during post-mortem aging of chicken Semitendinosus muscle-Contribution of structural weakening of intramuscular connective tissue to meat tenderization. AB - Post-mortem changes in endomysium and perimysium were investigated during aging of chicken semitendinosus muscle at 4 degrees C. Although the shear-force value of raw meat decreased rapidly within 5 h post mortem and gradually thereafter, the solubility of collagen and the ratio of each chain of soluble collagen remained unchanged during 24 h post mortem. Light microscopic studies showed that structures of endomysium and perimysium disintegrated into several thin sheets within 12 h post mortem, and that many gaps opened in the cross-section of endomysium and perimysium. While endomysium and perimysium were not stained by periodic acid Schiff reagent in fresh muscle, they were markedly stained in muscle 12 h post mortem. These results provide direct evidence for the structural weakening of endomysium and perimysium during post-mortem aging of chicken. Therefore, we conclude that the structural weakening of the intramuscular connective tissue is closely related to tenderization of chicken. PMID- 22059669 TI - Relationships between subjective and objective assessments of stress at slaughter and meat quality in pigs. AB - A study was carried out to relate subjective and objective measures of stress at slaughter and meat quality in pigs. Thirteen slaughter plants were visited. The systems used for handling the pigs pre-slaughter and the levels of stress experienced by the animals were subjectively assessed. The sound level immediately before stunning was also measured. Generally, systems that were rated as being most stressful also produced higher levels of sound, probably because of the vocalisations of the pigs. As the size of plant increased, there was a tendency for the level of stress, and the recorded sound level, to increase. This appeared to be because larger plants operated faster and were more likely to use restraining conveyors supplied by races to handle the animals before stunning. The restraint associated with these seems stressful to pigs. Five plants were selected for further study. Two had been assessed as having handling systems that produced a low level of stress in the pigs, one as having a system producing a medium level, and two as having poor systems producing high levels of stress. Blood samples were collected at exsanguination, and meat quality was assessed. As the level of subjectively assessed stress experienced by the pigs increased, so did the average blood levels of lactate and creatine phosphokinase (CPK). There was also a progressive increase in the potential incidence of pale, soft, exudative (PSE) and dark, firm, dry (DFD) meat in the plants using more stressful handling systems. Additionally, there were positive relationships between sound level and lactate and CPK, and sound level and indices of poorer meat quality. Cortisol concentrations were not different in pigs killed in the different systems and probably reflect events earlier in the handling process, such as in transport and lairage, rather than the stress experienced immediately before stunning. The overall conclusion was that subjective assessments of the stress suffered by pigs correlate well with objective measures and that higher stress levels are associated with poorer meat quality. PMID- 22059670 TI - Water activity of Spanish intermediate-moisture meat products. AB - On the basis of considering foods with water activity from 0.600 to 0.910 to be intermediate-moisture foods (IMF), we determined the water activity, pH, and some chemical parameters for 70 samples from 17 different selected types of Spanish intermediate-moisture meat products. Even though the salt content is the main water-activity depressor, the sodium chloride molality in the overall amount of water of the product cannot be used to calculate the a(w) value of these types of meat products of intermediate moisture. PMID- 22059671 TI - Measurements of pH(60) in pork using ISFET/REFET and glass electrode methods. AB - pH values of 180 pork longissimus dorsi muscles were obtained using different measurement methods. A glass combined penetration electrode and an ISFET/REFET pH sensor system were used directly in the muscle, whereas in the homogenate, pH was assessed with a glass combined electrode. The results showed that no statistically significant differences were obtained between the methods in all tested samples. However, samples where pH(60) stood below 5.9, produced a better agreement between methods. Comparing the values obtained from the two direct puncture methods in the first group of samples (pH<5.9) the I/R probe appeared to agree with those obtained from the homogenates. While working, the ISFET/REFET system proved to be a good device to detect carcasses with fast post mortem pH decline. Nevertheless, the excessive time required display stabilisation prohibits its use for continuous measurements on high speed slaughter-lines. PMID- 22059672 TI - Muscle pH(60), colour (L, a, b) and water-holding capacity and the influence of post-mortem meat temperature. AB - The use of the pH(60) and colour parameters (L, a, b) as chilled pork drip loss predictors 24 h post-mortem as well as the influence on this meat characteristic of an early blast cooling regime (90 min post-mortem) were investigated. Despite the best correlation found with pH(60) (-0.647), both indicators were found to be poor for this purpose, it being impossible to use them alone for pork quality classification (PSE/DFD status). Comparing the evolution between the drip losses on chilled and early deep frozen (-60 degrees C) longissimus dorsi pork cuts, the results indicate that both the thawing regime and the time the samples stay in refrigeration, influence the observed trends significantly. The general drip loss enhancement seen after thawing as well as the increasing meat toughness, judged subjectively, must be due to cold-shortening and/or thaw rigor phenomena. PMID- 22059673 TI - Relationship between Japanese beef marbling standard and intramuscular lipid in the M. longissimus thoracis of Japanese Black and American Wagyu Cattle. AB - Japanese Black and American Wagyu steers (n = 155) were slaughtered and graded under typical Japanese production conditions, and then analyzed for percentage ether-extractable fat at the 6th thoracic vertebra. The percentage of intramuscular lipid was used to develop a prediction equation for the Japanese beef marbling standard (BMS) with R(2) = 0.7619. PMID- 22059674 TI - Obituary: v. M. Gorbatov. PMID- 22059675 TI - Increasing incidence of Trichophyton tonsurans in Paris, France: a 15-year retrospective study. PMID- 22059676 TI - Dynamic SERS imaging of cellular transport pathways with endocytosed gold nanoparticles. AB - Dynamic SERS imaging inside a living cell is demonstrated with the use of a gold nanoparticle, which travels through the intracellular space to probe local molecular information over time. Simultaneous tracking of particle motion and SERS spectroscopy allows us to detect intracellular molecules at 65 nm spatial resolution and 50 ms temporal resolution, providing molecular maps of organelle transport and lisosomal accumulation. Multiplex spectral and trajectory imaging will enable imaging of specific dynamic biological functions such as membrane protein diffusion, nuclear entry, and rearrangement of cellular cytoskeleton. PMID- 22059677 TI - Assessing the confidence level of public domain compound activity data and the impact of alternative potency measurements on SAR analysis. AB - Publicly available compound activity data have been analyzed to distinguish between compounds for which single or multiple potency measurements were available and gain insight into data confidence levels. Different potency measurements with defined end points and alternative ways to represent multiple potency values for active compounds have been evaluated in the context of SAR analysis. Approximately 78% of all compounds with multiple potency measurements were found to represent high-confidence data, which corresponded to ~10% of all activity data. The use of different types of potency measurements and alternative representations of multiple potency values changed the SAR information content of compound data sets and resulted in different activity cliff distributions. Thus, the types of activity measurements that were available and how they were used substantially impacted SAR analysis. Compounds with multiple K(i) measurements provided the most reliable basis for SAR exploration. PMID- 22059678 TI - Super-resolution microscopy reveals cell wall dynamics and peptidoglycan architecture in ovococcal bacteria. AB - Cell morphology and viability in Eubacteria is dictated by the architecture of peptidoglycan, the major and essential structural component of the cell wall. Although the biochemical composition of peptidoglycan is well understood, how the peptidoglycan architecture can accommodate the dynamics of growth and division while maintaining cell shape remains largely unknown. Here, we elucidate the peptidoglycan architecture and dynamics of bacteria with ovoid cell shape (ovococci), which includes a number of important pathogens, by combining biochemical analyses with atomic force and super-resolution microscopies. Atomic force microscopy analysis showed preferential orientation of the peptidoglycan network parallel to the short axis of the cell, with distinct architectural features associated with septal and peripheral wall synthesis. Super-resolution three-dimensional structured illumination fluorescence microscopy was applied for the first time in bacteria to unravel the dynamics of peptidoglycan assembly in ovococci. The ovococci have a unique peptidoglycan architecture and growth mode not observed in other model organisms. PMID- 22059679 TI - What does dual pathway Wenckebach mean? PMID- 22059680 TI - Ultrastructural findings on the skeletal muscles of pigs following ultrarapid chilling in the initial phase of meat maturation. AB - The purpose of this study was to show the structural alterations in the short term frozen surface musculature of slaughtered pigs followed ultrarapid chilling methods. In muscles with normal glycolysis the short-term freezing of the musculature following ultrarapid chilling within 3 h 45 min post mortem led to cold shortening and in some areas to considerable changes in the transverse striation. The interstitial and interfibrillar spaces revealed severe oedema. The organelles showed, almost without exception, extreme vacuolar alterations and the cell membranes appeared fragmented. The non-frozen musculature of the more slowly chilled control group revealed similar changes but of a minor or less serious nature. In the muscle samples with accelerated glycolytic rates only minor differences were observed between the ultrarapidly chilled and the control musculature. Final evaluation of the effect of these chilling methods can only take place after studying the influence of the ultrastructural changes on the water binding capacity and tenderness of the musculature. PMID- 22059681 TI - Effect of different electrical stimulation and chilling treatments on pork quality. AB - The effect of different chilling and electrical stimulation (ES) treatments on the carcass and eating quality of pork has been examined. Preliminary trials (Study I), with a variety of ES treatments, indicated that, on the basis of pH fall, drip loss and tenderness, the most effective was that using 700 V peak at 12.5 Hz for 90 s applied at 20 min post-slaughter. These ES parameters were used throughout the main study (II) using 80 pigs, one side of which was stimulated and the other not, before being chilled rapidly (10 degrees C in deep loin within 2-3 h of slaughter) or conventionally (10 degrees C in deep loin within 5 h of slaughter). Changes in pH and temperature during chilling were observed and, after chilling, quality assessments on LD and Sm muscles included drip loss, muscle opacity and instrumental toughness at 3 days post-slaughter. Electrical stimulation, 20 min post-slaughter, improved tenderness of the LD and, to a lesser extent, the Sm of rapidly chilled pig sides. This advantage was gained without producing PSE pork. In fact, drip loss from the LD was consistently less from the sides which had been stimulated. PMID- 22059682 TI - The effect of ractopamine on myofibre distribution and morphology and their relation to meat quality in swine. AB - One hundred and twenty-eight purebred Lacombe pigs (equal number of barrows and gilts) were assigned to one of four treatments at 64 kg and fed a commercial grower-finisher diet ad libitum to which ractopamine (RAC) was incorporated (0, 10, 15 or 20 mg kg(-1)). Pigs were slaughtered at 100 kg. Histological samples were collected from the semimembranosus (SM) and the psoas major (PM) muscles from the 0 and 20 mg kg(-1) RAC groups. Meat quality and muscle composition data were collected for all pigs. A significant 3-way interaction for muscle weight involving treatment, muscle and gender (P = 0.01) indicated that for the SM, gilts appeared to respond to RAC at a lower level of incorporation (10 mg kg(-1)) than barrows. Despite these differences in response at the gross muscle level, responses were similar at the cellular level for both muscles. The proportion of red fibres did not change (P = 0.21), the proportion of intermediate fibres decreased (P = 0.01) and the proportion of white muscle fibres increased (P = 0.02) in the mg kg(-1) RAC group compared to the controls. In addition, when compared to controls, average fibre diameters in the 20 mg kg(-1) RAC group remained constant in the red fibres, and increased significantly in both the intermediate and white fibres (P = 0.01 and 0.02, respectively). Over both muscles Kramer Press values were significantly higher (P = 0.030 in the RAC-fed pigs than in the controls. Incorporation of RAC into the diet did not result in any changes to crude protein or total and soluble hydroxyproline levels. Crude fat tended to increase in the 15 mg kg(-1) RAC treatment in the SM and decreased in the 20 mg kg(-1) RAC treatment in the PM. The shift in fibre type, and the associated changes in fibre size, may contribute to the increased shear values found in RAC-fed pigs. PMID- 22059683 TI - Distribution of volatile branched-chain fatty acids in various lamb tissues. AB - Volatile fatty acids (C4-C11) including even-, odd-, and branched-chain members in lamb tissues were quantitatively analyzed. Volatile branched-chain fatty acids (BCFA) were more concentrated in subcutaneous adipose tissue samples (rump, shoulder, breast) than in perinepheric adipose or muscle tissues. Perinepheric adipose tissue contained relatively high quantities of n-chain, even-numbered fatty acids and very low levels of BCFA. Greater variation existed in fatty acid profiles among similar subcutaneous adipose tissues from different lambs than between samples of adipose tissue from different carcass sites from a given lamb sample. 4-Methyl- and 4-ethyloctanoic acids were present at concentrations greatly above threshold levels in all lamb fats tested, and thus upon hydrolysis would contribute species-related flavors to lamb. 4-Methylnonanoic concentrations in lamb fats ranged from nondetectable to greater than the threshold level, and therefore this compound would not always contribute to the species-related flavors of lamb. Lean meat samples contained very low concentrations of 4-methyl- and 4-ethyloctanoic acids. PMID- 22059684 TI - The Use of principal component analysis (PCA) for evaluating results from pig meat quality measurements. AB - The relationships between different meat quality methods, i.e. pH, meat colour, protein extractability and pigment content, measured on Swedish pig carcasses, were analysed by principal component analysis (PCA). The result indicated that when using PCA for selection among the meat quality methods used, the ultimate internal reflectance explained the greatest proportion of the total variance. The results of this study show that PCA is a simple method of finding objects with different characteristics (e.g. outliers and various quality classes) and for variable selection. PMID- 22059685 TI - Secondary sexual development (Masculinity) of bovine males: 1. Influence on carcass composition, cutability, economic value and certain muscles. AB - Differences in carcass composition, cutability, economic value of the carcass and distribution of certain muscle groups, between bulls with secondary sexual characteristics (bulls(+)), those without (bulls(-)), and steers were investigated. Two carcass mass groups (250-300 and 301-350 kg) were compared. Five carcasses of either mass group were studied within each sex condition group. Bulls(+) had a higher meat percentage (P < 0.05) than bulls(-) or steers. They also had a lower bone percentage than steers (P < 0.05), but non-significant differences were found between bulls(+) and bulls(-) for bone percentage. Significant differences (P < 0.05) between sex condition groups were found for percentages of hindquarter, as well as for distribution of high-priced cuts. Steers had the most favourable distribution and bulls(+) the least favourable. Bulls(-) were intermediate. Masculinity significantly (P < 0.05) influenced the distribution of the chuck, neck, brisket and hind shin cuts, whilst mass had a significant effect on the percentage hind shin and percentage thin flank. It was found that the M. rhomboideus was the only muscle of those studied that was significantly affected by masculinity and it was concluded that this muscle could be used as an indicator of the masculinity of the carcass. The economic values of the carcasses of steers, bulls without secondary sexual development and bulls with secondary sexual development differed non-significantly. PMID- 22059686 TI - Secondary sexual development (Masculinity) of bovine males: 2. Influence on certain meat quality characteristics. AB - Differences in meat quality traits between bulls with secondary sexual development (bulls(+), n = 10), those without this development (bulls(-), n = 10) and steers (n = 10) were investigated. All animals had no permanent incisors (A age group). Significant differences (P < 0.05) between bulls(+) and bulls(-) were found for the cooking loss percentage of the M. splenius (27.83% versus 31.11%, respectively), iron content of the M. splenius (56.02MUg/g versus 49.43MUg/g, respectively) and total collagen content of the M. splenius (3.74 versus 4.73 measured as Hyp N/Tot N x 1000, respectively). Drip loss of the wingrib cut (4.01% versus 5.18%, respectively) was also significantly different between bulls(+) and bulls(-). For the M. longissimus thoracis, no significant (P < 0.05) differences in any of the quality-indicating parameters investigated could be found. It is concluded that the M. splenius can be used as an indicator muscle for masculinity, based on meat quality attributes. This is supported by the correlation coefficients obtained between masculinity and the intramuscular collagen content of the M. splenius (r = -0.55) and the iron content of the M. splenius (r = 0.46). For all the other quality attributes investigated, non significant (P > 0.05) differences between the three sex condition groups were found. It is concluded that the influence of masculinity on meat quality traits of young bulls is of little practical importance in a classification and grading system. PMID- 22059687 TI - Survival of ropy slime-producing lactic acid bacteria in heat processes used in the meat industry. AB - The study reported here deals with the survival of ropy slime-producing lactic acid bacteria in two different heat processes used in the Finnish meat industry. In both processes tested, ropiness was prevented in products inoculated with the bacteria before cooking. The bacterial count in the sausages decreased during processing over 4-5 log units/g. The bacteria were evidently unable to survive the processes, and the contamination of the products apparently takes place after cooking. Heat treatment given to vacuum-packed grill sausages after packing could delay the formation of ropy slime. PMID- 22059688 TI - Effect of dietary crude protein content on skatole concentration in boar serum. AB - Forty-eight Yorkshire * Chester White crossbred boars, 28 days of age, were assigned to one of four diets differing in crude protein content. Dietary crude protein content was 23% initially and then adjusted to 14, 17, 20 or 23% at 9 weeks of animal age, and 12, 15, 18 or 21% at 14 weeks of age, respectively. The skatole concentrations in serum of the boars was measured at 24, 32 and 40 weeks of age. Results showed that serum skatole concentrations declined (P < 0.05) with increasing age (0.034, 0.027 and 0.021 MUg/ml at 24, 32 and 40 weeks, respectively) and also decreased (P < 0.059) with increasing dietary crude protein concentration (0.033, 0.026, 0.022 and 0.021 MUg/ml at 12, 15, 18 and 21% in finishing diets, respectively). PMID- 22059689 TI - The effectiveness of high frequency electrical stunning in pigs. AB - Two commercially-available high frequency electrical stunners producing either AC sinewaves (146 V; 1592 Hz) or DC squarewaves (162V; 1642 Hz) having different waveforms were tested for their effectiveness in stunning pigs and compared with conventional 50 Hz sinusoidal waveforms. Seventy-nine pigs were stunned using the highest voltage settings, allowed to recover, and the duration of insensibility was assessed from behavioural signs. It was found that the pigs were adequately stunned by this method even though some physical responses differed from 50 Hz stunning. An additional experiment was conducted on three pigs to examine whether the epileptic brain activity (indicative of unconsciousness) occurred following high frequency stunning and to assess the effects on visually evoked responses. It was confirmed that high frequency stunning produced epilepsy and unconsciousness and appeared therefore to be acceptable from an animal welfare standpoint. However, the average stunning to sticking intervals were shorter with high frequency stunning compared with 50 Hz stunning. PMID- 22059690 TI - Individualized prediction of illness course at the first psychotic episode: a support vector machine MRI study. AB - BACKGROUND: To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode. METHOD: One hundred patients at their first psychotic episode and 91 healthy controls had an MRI scan. Patients were re evaluated 6.2 years (s.d.=2.3) later, and were classified as having a continuous, episodic or intermediate illness course. Twenty-eight subjects with a continuous course were compared with 28 patients with an episodic course and with 28 healthy controls. We trained each SVM classifier independently for the following contrasts: continuous versus episodic, continuous versus healthy controls, and episodic versus healthy controls. RESULTS: At baseline, patients with a continuous course were already distinguishable, with significance above chance level, from both patients with an episodic course (p=0.004, sensitivity=71, specificity=68) and healthy individuals (p=0.01, sensitivity=71, specificity=61). Patients with an episodic course could not be distinguished from healthy individuals. When patients with an intermediate outcome were classified according to the discriminating pattern episodic versus continuous, 74% of those who did not develop other episodes were classified as episodic, and 65% of those who did develop further episodes were classified as continuous (p=0.035). CONCLUSIONS: We provide preliminary evidence of MRI application in the individualized prediction of future illness course, using a simple and automated SVM pipeline. When replicated and validated in larger groups, this could enable targeted clinical decisions based on imaging data. PMID- 22059691 TI - Integrated care facilitation model reduces use of hospital resources by patients with pediatric asthma. AB - This evaluation assessed a model of care for pediatric asthma patients that aimed to promote health and reduce their preventable and avoidable use of acute hospital services. Pediatric asthma patients (n=223) were allocated care facilitators who provided assistance in the promotion of carer/self-management, education and linkage to an integrated healthcare system, comprising of acute and community-based healthcare providers. Patients' use of acute hospital services (emergency department [ED] presentations, admissions, and bed-days) pre- and postrecruitment were compared using Wilcoxon signed rank tests. The pediatric asthma care givers quality of life questionnaire' was used to assess changes in health and quality of life. The patients displayed a 57% reduction in ED presentations, 74% in admissions, and a 71% reduction in bed-days. Whereas a comparator group displayed 27%, 32%, and 14% increases, respectively. Patients also reported significant improvements in quality of life domains of activity limitation (+5.6, p<.001) and emotional function (+9.1, p<.001). The reduction in the use of hospital services was attributed to the aversion of preventable presentations and admissions, via the enhancement of carer/self-management and access to community health services. These outcomes were supported by indicators of improved patient health and quality of life, and comments by the participant's carers. PMID- 22059692 TI - Survival of Deinococcus radiodurans against laboratory-simulated solar wind charged particles. AB - In this experimental study, cells of the radiation-resistant bacterium Deinococcus radiodurans were exposed to several different sources of radiation chosen to replicate the charged particles found in the solar wind. Naked cells or cells mixed with dust grains (basalt or sandstone) differing in elemental composition were exposed to electrons, protons, and ions to determine the probability of cell survival after irradiation. Doses necessary to reduce the viability of cell population to 10% (LD(10)) were determined under different experimental conditions. The results of this study indicate that low-energy particle radiation (2-4 keV), typically present in the slow component of the solar wind, had no effect on dehydrated cells, even if exposed at fluences only reached in more than 1000 years at Sun-Earth distance (1 AU). Higher-energy ions (200 keV) found in solar flares would inactivate 90% of exposed cells after several events in less than 1 year at 1 AU. When mixed with dust grains, LD(10) increases about 10-fold. These results show that, compared to the highly deleterious effects of UV radiation, solar wind charged particles are relatively benign, and organisms protected under grains from UV radiation would also be protected from the charged particles considered in this study. PMID- 22059693 TI - Life on Venus. PMID- 22059694 TI - Effect of the antipsychotic agent amisulpride on glucose lowering and insulin secretion. AB - AIMS: To investigate the effects of the second generation antipsychotic (R/S) amisulpride, and the chirally purified enantiomers, on glucose homeostasis in diet-induced obese (DIO) mice. METHODS: Normal and DIO mice were treated with pharmacologically relevant doses of amisulpride prior to oral glucose tolerance tests (OGTTs). Blood glucose, insulin, glucagon-like peptide-1, prolactin and amisulpride drug levels were determined. RESULTS: Racemic amisulpride significantly reduced glucose excursions during OGTT in both normal and DIO mice. This potent effect was preserved with the 'off-isomer', R-amisulpride (ED(50) 1 mg/kg). Insulin secretion was significantly increased with R-amisulpride with only a minor increase in prolactin levels. CONCLUSIONS: Amisulpride has antidiabetic actions in DIO mice resulting from increased insulin secretion. This provides some explanation for why amisulpride, unlike other atypical antipsychotics, is not diabetogenic in man. Furthermore, the observation that R amisulpride is also antidiabetic and has minimal impact on prolactin levels presents the opportunity for development of this isomer as an antidiabetic agent. PMID- 22059695 TI - Reflections on the journey: six short stories. AB - One of the goals of the 2011 International Year of Chemistry is to celebrate the contributions of women to science. A question that has been frequently asked in this regard is... Why is it necessary to highlight women in the "age of equality"? The reasons are varied but the facts are that many women scientists worked in obscurity throughout the 19th and even well into the 20th century, sometimes publishing anonymously to be heard. This celebration of Women in Science is one way to recognize both the resiliency and passion of these women. As part of this celebration, Chemistry Central Journal's Thematic Series of "Women in Chemistry" includes this article describing the path several women took as they pursued chemistry careers spanning the latter part of the 20th century and into the early 21st century. Sharon Haynie, Nancy Jones, Cheryl Martin, Paula Olsiewski, Mary Roberts and Amber Hinkle each have unique story of their personal journey from childhood to adulthood. As you read these stories, listen generously, and feel free to share your own stories, comments and thoughts. PMID- 22059696 TI - The quality and use of regulatory analysis in 2008. AB - This article assesses the quality and apparent use of regulatory analysis for economically significant regulations proposed by federal agencies in 2008. A nine member research team used a six-point (0-5) scale to evaluate regulatory analyses according to criteria drawn from Executive Order 12866 and Office of Management and Budget Circular A-4. Principal findings include: (1) the average quality of regulatory analysis, though not high, is somewhat better than previous regulatory scorecards have shown; (2) quality varies widely; (3) biggest strengths are accessibility and clarity; (4) biggest weaknesses are analysis of the systemic problem and retrospective analysis; (5) budget or "transfer" regulations usually receive low-quality analysis; (6) a minority of the regulations contain evidence that the agency used the analysis in significant decisions; (7) quality of analysis is positively correlated with the apparent use of the analysis in regulatory decisions; and (8) greater diffusion of best practices could significantly improve the overall quality of regulatory analysis. PMID- 22059697 TI - Nonlinear Heart Rate Variability features for real-life stress detection. Case study: students under stress due to university examination. AB - BACKGROUND: This study investigates the variations of Heart Rate Variability (HRV) due to a real-life stressor and proposes a classifier based on nonlinear features of HRV for automatic stress detection. METHODS: 42 students volunteered to participate to the study about HRV and stress. For each student, two recordings were performed: one during an on-going university examination, assumed as a real-life stressor, and one after holidays. Nonlinear analysis of HRV was performed by using Poincare Plot, Approximate Entropy, Correlation dimension, Detrended Fluctuation Analysis, Recurrence Plot. For statistical comparison, we adopted the Wilcoxon Signed Rank test and for development of a classifier we adopted the Linear Discriminant Analysis (LDA). RESULTS: Almost all HRV features measuring heart rate complexity were significantly decreased in the stress session. LDA generated a simple classifier based on the two Poincare Plot parameters and Approximate Entropy, which enables stress detection with a total classification accuracy, a sensitivity and a specificity rate of 90%, 86%, and 95% respectively. CONCLUSIONS: The results of the current study suggest that nonlinear HRV analysis using short term ECG recording could be effective in automatically detecting real-life stress condition, such as a university examination. PMID- 22059698 TI - Anterior and posterior reconstruction technique and its impact on early return of continence after robot-assisted radical prostatectomy. AB - BACKGROUND AND PURPOSE: Urinary incontinence is a significant cause of morbidity after robot-assisted radical prostatectomy (RARP). Several techniques have been developed to improve continence rates. In this study, we compared the continence rates of patients who underwent RARP with total reconstruction and without reconstruction. PATIENTS AND METHODS: Between March 2005 and September 2009, 245 patients underwent RARP at our institution. The initial 120 patients (control group) underwent standard RARP without reconstruction and the last 125 patients (reconstruction group) underwent a total reconstruction technique, which included an anterior and posterior reconstruction. Patients were followed for 1, 4, 12, 24, 36, and 52 weeks after the operation. Continence was defined with strict criteria-no usage of pads and no leakage of urine. RESULTS: In the reconstruction group, the continence rates at, 1, 4, 12, 24, 36, and 52 weeks postoperatively were 71%, 72%, 80%, 84%, 86%, and 91%, respectively; in the control group, the continence rates were 23%, 49%, 76%, 80%, 85%, and 88%, respectively. CONCLUSION: The overall continence rates were similar in both groups at 52 weeks of follow up. Patients in the total reconstruction group, however, had higher early continence rates compared with patients in the control group. The total reconstruction procedure is an efficient way to achieve an early return to continence. PMID- 22059699 TI - Diastereo- and enantioselective catalytic vinylogous Mukaiyama-Mannich reactions of pyrrole-based silyl dienolates with alkyl-substituted aldehydes. AB - A reliable, catalytic asymmetric vinylogous Mukaiyama-Mannich reaction of pyrrole based silyl dienolates is introduced that is particularly apt for alkyl- and alpha-alkoxyalkyl-substituted aldehydes. The reaction course is effectively orchestrated by the Hoveyda-Snapper amino acid-based chiral ligand/silver(I) catalyst combination to produce valuable vicinal diamino carbonyl compounds in high yields, with virtually complete gamma-site- and anti-selectivity and significant catalyst-to-product chirality transfer. The utility of the Mannich products can be seen in the synthesis of an unprecedented perhydrofuro[3,2 b]pyrrolone product, an aza-analogue of naturally occurring (+)-goniofufurone. PMID- 22059701 TI - Effects of nutritional planes and brees on intramuscular-lipid deposition in M. longissimus dorsi of steers. AB - The influences of nutritional planes and breeds on intramuscular-lipid (IML) deposition in M. longissimus dorsi were investigated by comparing the relationships between intramuscular lipid percentages (IMLP) in the muscle and side-carcass weight (SCW), carcass-fat percentage (CFP), and slaughter age (SA). Japanese Black (JB) and Japanese Shorthorn (JS) steers were fattened under two (medium-high and high) nutritional planes, which were different only in JB and when the adjusted IMLPs were compared on the basis of SCW or CFP. Breed effects on IML deposition were investigated by using three pure breeds and four crossbred steer groups. The means of IMLPs in the muscle adjusted to three criteria were significantly different among breeds, the IMLPs of JB and their backcrosses being higher than those of JS and Charolais crosses. IML deposition in steers was highly dependent on the genetic potential of the breeds or bulls used. PMID- 22059700 TI - Real-time PCR to quantify composition of arbuscular mycorrhizal fungal communities--marker design, verification, calibration and field validation. AB - Quantitative real-time PCR (qPCR) is slowly becoming established as a tool to quantify abundance of different arbuscular mycorrhizal fungal (AMF) taxa in roots and in soil. Here, we describe the development and field validation of qPCR markers (i.e. primers with associated hydrolysis probes), targeting taxon specific motifs in the nuclear large ribosomal subunit RNA genes. Design of such markers is complicated by the multinuclear and multigenomic cellular organization of these fungi and the high DNA sequence diversity within the smallest biologically relevant units (i.e. single-spore isolates). These limitations are further compounded by inefficient biomass production of these fungi, resulting in limited availability of pure genomic DNA (gDNA) of well-defined isolates for cross-specificity testing of the markers. Here we demonstrate, using a number of AMF isolates, the possibility to establish stringent qPCR running conditions allowing quantification of phylogenetically disjunctive AMF taxa. Further, we show that these markers can more generally be used to quantify abundance (i.e. number of target gene copies or amount of gDNA) of what is usually considered the level of AMF species, regardless of the isolate identities. We also illustrate the range of variation within qPCR signal strength across different AMF taxa with respect to the detected number of gene copies per unit amount of gDNA. This information is paramount for interpretation of the qPCR analyses of field samples. Finally, the field validation of these markers confirmed their potential to assess composition of field AMF communities and monitor the changes owing to agricultural practices such as soil tillage. PMID- 22059702 TI - Identification of halothane genotypes by calcium accumulation and their meat quality using live pigs. AB - The three halothane genotypes (NN, Nn, and nm) were identified by measuring the capacity for Ca(2+) accumulation by sarcoplasmic reticulum in whole muscle homogenate preparations of M. longissimus dorsi with a Ca(2+) specific electrode at 35 degrees C. Significant differences (P < 0.001) in deterioration (%) of Ca(2+) accumulation, 12% for NN, 35% for Nn, and 81% for nn pigs, were observed after ageing the whole muscle homogenate preparations for 24 h in ice. Predictions of meat quality in live pigs (n = 34) based on the values for water holding capacity, assessed as fluid (g/0.5 g wet wt LD), and pH (fluid) by using small biopsy LD samples (Cheah et al. 1993) were performed on all the halothane genotypes. The halothane genotype NN (n = 11) showed a fluid value of 0.37 +/- 0.01 and a pH (fluid) value of 6.62 +/- 0.03 as compared with 0.61 +/- 0.02 and 5.84 +/- 0.04, respectively, for the halothane genotype nn (n = 13). The Nn pigs (n = 10) showed fluid (0.49 +/- 0.03) and pH (fluid) (6.19 +/- 0.11) values between those values observed for the two homozygotes (NN and nn). Predictions of meat quality in live pigs from biopsy LD muscles were confirmed from assessments on post-mortem LD muscles based on pH(1) and fibre optic probe (FOP) measurements. The extent of deterioration (%) in Ca(2+) accumulation showed high correlations with fluid (r = -0.861) and pH (fluid) (r = -0.831) in the biopsy LD samples, and with pH(1) (r = 0.663), FOP (r = -0.812), and drip (%) loss (r = 0.777) in the post-mortem LD samples. PMID- 22059703 TI - The display life of retail-packaged beef steaks after their storage in master packs under various atmospheres. AB - Beef strip loins were divided into four portions. One portion of each loin was vacuum-packaged and then stored at -1.5 degrees C. The other portions were each divided into three steaks, which were retail-packaged. The retail packs were master-packaged under atmospheres of N(2), CO(2), or O(2) + CO(2) (2 : 1, v/v) and then stored at 2 degrees C. Product was assessed after storage times of up to 60 days. At each assessment, a vacuum pack and a master pack of each type, each containing product from the same loin, were withdrawn from storage. The vacuum packaged product was cut into three steaks, which were retail-packaged. The newly prepared retail packs and those from the master packs were displayed in a retail cabinet, at air temperatures that averaged between 3 and 5.7 degrees C, and were assessed twice daily until the product was judged to be unacceptable. When first assessed, steaks cut from vacuum-packaged product were generally considered desirable, with little metmyoglobin in the surface pigment, although the edges of same steaks were discoloured. Steaks stored under N(2) or CO(2) for 4 days or less were only slightly desirable at best, with metmyoglobin forming relatively large fractions of the surface pigment. However, after storage under N(2) or CO(2) for 6 days or more, metmyoglobin fractions were low, and the steaks bloomed to a desirable red colour. Steaks stored under O(2) + CO(2) had lower metmyoglobin fractions, and were desirable after storage for up to 8 days. However, the fractions of metmyoglobin increased, and steaks were judged to be less desirable after longer storage times. Steaks stored under O(2) + CO(2) for 20 days were unacceptable. After storage, the numbers of bacteria on steaks from vacuum packs and N(2), CO(2), and O(2) + CO(2) atmospheres were, respectively, <10(4), <10(6), <10(5), and <10(4) CFU/cm(2). The flora from steaks stored under CO(2) were composed wholly of lactic acid bacteria. Other flora were dominated by lactic acid bacteria, but contained fractions of enterobacteria and/or Brochothrix thermosphacta. The appearance of product from vacuum packs generally was unacceptable after 72 h of display. The display life of steaks stored under N(2) or CO(2) was shorter than that of the product from vacuum packs when product was stored for 2 days or less, or 46 days or more. After other storage times, the product from vacuum packs or master packs with N(2) or CO(2) atmospheres had a similar display life. The display life of product stored under O(2) + CO(2) was similar to that of product from vacuum packs or CO(2) or O(2) + CO(2) was similar to that of product from vacuum packs after storage times of 8 days or less but was shorter after storage times of 12 or 16 days. The flora on displayed product from vacuum packs or CO(2) or O(2) + CO(2). atmospheres did not attain the maximum number of 10(7) CFU/cm(2). and the product did not develop off-odours of microbial origin. However, numbers of 10(7) CFU/cm(2) were approached or attained during display of product stored under N(2) for 28 days or longer, and some of that product developed moderate off-odours. It then appears that, under temperature regimes that are common in commercial practice, retail-packaged strip loin steaks with a display life of 2 days or longer can be obtained from master packs after storage periods of up to about 2, 4, or 7 weeks, respectively, with master-pack atmospheres of O(2) + COPin2 (2 : 1, v/v), N(2), or CO(2). PMID- 22059704 TI - Consumer acceptance of display packs of beef stored under N(2) or CO(2) in master packs. AB - Display-packaged samples of beef steak and of ground beef were delivered to the homes of 120 panelists. Each panelist received a set of samples of each meat. Each set consisted of one sample freshly prepared for retail display from vacuum packaged product, one retail-packaged and then stored in a master pack under N(2) and one retail-packaged and the stored under CO(2). The samples in each set were prepared from the same strip loin or batch of coarsely ground beef and had been stored for between 21 and 23 days at 2 degrees C. The panelists completed questionnaires on the attributes of the meats while they were packaged, when they were unpackaged for cooking, and when they were eaten. The responses to each question were tabulated, and the probability of the chi(2) statistics was calculated for each table. There were no significant differences in the general acceptability of the steaks from the three storage treatments. Significant numbers of panelists judged that ground beef prepared from vacuum-packaged product was of better colour and had less exudate, but was of poorer eating quality than the product from master packs. However, the majority of panelists did not distinguish between ground beef from the three storage treatments. The consumer responses indicate that controlled-atmosphere master packaging of display packs may offer a means of preserving display-ready beef for times that would allow wide distribution of the product through current commercial systems. PMID- 22059705 TI - Effects of Kramer-shear-press-test conditions on the shear properties of beef products. AB - Tenderness parameters of bologna, salami, and pastrami were measured by Kramer shear tests. Three levels of sample size and crosshead speed were used. The initial yield force did not change significantly as the sample size changed. The friction between the sample and press, and the sample's stress and strain changes, were studied to explain the effect of sample size on shear properties. Peak-force distance (PD) increased proportionally to the increase in fill percentage. Peak force (PF) and initial-yield distance (IYD) increased partly as the fill percentage increased. The slope changed with the change in IYD, and break area (BA) changed proportionally to the changes in PF and PD. Recommended test conditions for bologna are 50% fill percentage at any crosshead speed; those for salami are 25% fill percentage at 150-mm/min crosshead speed; and those for pastrami are 75% fill percentage at 250-mm/min crosshead speed. PMID- 22059706 TI - Carcass and meat quality of finishing Friesian steers fed the beta-adrenergic agonist L-644,969. AB - The effect of the beta-adrenergic agonist L-644,969 on selected parameters of carcass and meat quality was examined in Friesian steers. Four groups of 18 steers were individually offered ad libitum a pelleted diet that contained 0, 0.25, 1.0, or 4.0 ppm L-644,969 for 12 weeks prior to slaughter. L-644,969 quadratically increased carcass weight (3.7, 9.3, and 8.5%, P < 0.001) and altered the distribution of lean meat such that a greater (0.3-5%; P < 0.01) proportion was in the more valuable cuts. There were no effects of L-644,969 on carcass-chill loss and on the water-holding capacity of the longissimus thoracis et lumborum (LTL) muscle. The intramuscular-fat concentration of the LTL was decreased (27-50%; P < 0.01) and the effects on muscle ultimate pH were small and commercially unimportant. Fibre-optic-probe measurements of the LTL indicated darker (P < 0.01) meat due to beta-agonist treatment. L-644,969 increased the shear force required to cut through cooked muscle from the LTL (159%, 209%, and 217%, P < 0.001). It is concluded that L-644,969 treatment improved the quantity and distribution of lean in the carcass but impaired meat quality, primarily through a reduction in tenderness. PMID- 22059707 TI - Electrical stunning by direct brain stimulation in pigs. AB - The effects of electrical stunning of slaughter pigs by electrodes shot into the brain, on sensibility and on the incidence of haemorrhages in the shoulder postmortem, were studied. To determine the efficiency of this method 37 slaughter pigs were equipped with EEG (electroencephalograph) and ECG (electrocardiograph) electrodes and stunned twice via the EEG electrodes. In the first experiment the pigs were stunned with 25 V and in the second with 25 V followed by a relaxation current. The day after slaughter the shoulders were scored for haemorrhages. Under more practical conditions three groups of 10 pigs each were electrically stunned via electrodes shot into the brain using 25, 50 or 75 V, followed by a relaxation current. The day after stunning the shoulders were scored for haemorrhages. The pigs did not react to shooting electrodes frontally into the head. After stunning all animals showed a general epileptiform seizure. However, after the second stun the tonic and clonic muscle cramps were impaired. The heart rate increased significantly (P < 0.01) after stunning, and extra systolae and irregular heart rates were observed. In the shoulders of 27% of the carcasses no haemorrhages were found and in the remainder only minor haemorrhages were seen. Under practical conditions a voltage of 87(+/- 2) V and a current of 511(+/-20) mA seemed to be necessary for an effective stun. When lower voltages were applied fewer carcasses with shoulder haemorrhages were found. It may be concluded from these experiments that 25 V (~134 mA; 150 Hz) is sufficient for effective stunning of slaughter pigs when electrodes are in direct contact with the brain. But as the optimum position of the electrodes may not be reached under practical conditions a voltage of approximately 90 V (~550 mA; 150 Hz) is recommended. After this stunning method only a few haemorrhages were observed in the shoulders. PMID- 22059708 TI - Evaluation of calcium chloride and lactic acid injection on chemical, microbiological and descriptive attributes of mature cow beef. AB - The effect of calcium chloride, lactic acid or their combination on palatability, microbiological, and flavor characteristics of mature cow semimembranosus muscle was investigated. Regardless of aging time, a 10% injection of equal volumes of 0.3 m calcium chloride and 0.3 m lactic acid into hot-boned semimembranous muscle improved (P < 0.05) shear force values (approximately 35%) compared to hot- and cold-boned control cuts. Microbiological characteristics for all treatments were similar. Control cuts retained more desirable flavor (beefy and serumy/bloody) and less off-flavor (liver, sour, bitter and astringent) than calcium-chloride- or lactic-acid-injected cuts. PMID- 22059709 TI - Changes in lightness of porcine lean meat batters during processing. AB - The pattern of changes of lightness (L(*)) for porcine lean meat batters (PLMBs) with time was divided in two phases: chopping process (Phase 1) resulting in a sharp increase of L(*), and the subsequent storage of the batters for 24 h at 15 degrees C (Phase 2). During Phase 2, L(*)-values decreased with time approximating a plateau. The subjects of study were effects on the course of L(*) of: (1) added sodium chloride and phosphate in Phase 2, (2) the fate of air bubbles embedded in the batters in Phases 1 and 2, and (3) changes in light absorption by the pigment myoglobin in Phase 2. (1) Sodium chloride and phosphate appeared to have very little impact on the changes in L(*) during storage of the PLMBs at 15 degrees C, although microstructural changes were distinct. (2) Continuous entrapment of air during the chopping process had a major effect on the increase of L(*) in Phase 1, air bubbles being scattering elements in the PLMB. Disproportionation caused a decrease in the number of small air bubbles, resulting in a decrease of L(*) during the early stage of Phase 2 (about 35 min), immediately after the chopping stage was finished. (3) Strong evidence was obtained that shifts in the absorption traits of pigments (red nitric oxide myoglobin was formed at the cost of grey met-myoglobin) during the period from 1 to 5 h, caused a marked decrease in the pattern of L(*) during Phase 2. PMID- 22059710 TI - The effect of post-exsanguination infusion on the composition, exudation, color and post-mortem metabolic changes in lamb. AB - Twenty-four lamb carcasses were assigned to three treatment groups: (1) control (Ctr), (2) infused with 10% (vol/wt) of a tenderizing blend (NCa), and (3) NCa plus 0.015 m CaCl(2) (WCa). Results indicated that the infused carcass solution was retained in the following order: shoulder > lion > leg. Infusion had no effect (P > 0.05) on drip and cooking losses in refrigerated samples. Samples frozen and then thawed from infused carcasses had greater thaw drip (P < 0.05) and cooking losses (P < 0.01) than control samples. The amounts of drip and cooking losses were in the order: WCa > NCa > Ctr. Frozen storage preserved the red color but lowered the lightness and yellowness of ovine muscles; the opposite effect was observed following refrigerated storage. Infused samples were lighter and yellower than control in both fresh and frozen samples (P < 0.01). WCa had less red color (P < 0.01) than NCa and Ctr at all times and storage conditions. Infusion lowered (P < 0.05) the temperature of carcasses over the first 3 h postmortem (pm) compared with Ctr. The rate of glycolysis was higher in infraspinatus (IS) than in longissimus thoracis et lumborum muscle (LTL or longissimus). In both IS and LTL, glycolysis was completed within the first 6 h postmortem in NCa, whereas in Ctr and WCa, it took 12-24 h for glycolysis to be completed. The rate of glycolysis was in the order: NCa > WCa > Ctr. PMID- 22059711 TI - Composition of minced meat part A: Methods. AB - A simplified rapid electrophoretic method is described for the identification of venison, pork, and beef in samples of only a few grams of minced meat. The method is based on the species-specific separation patterns obtained upon electrophoresis of the proteins. Venison, beef, and pork can be identified easily and readily from the patterns given by their raw water-extractable proteins. PMID- 22059712 TI - Composition of minced meat part B: A survey of commercial ground meat. AB - A modified polyacrylamide-gel electrophoretic method was used to differentiate qualitatively various species of meat such as beef, pork, venison, reindeer, and mutton. The composition of commercial minced meat was examined; and illegal adulterations of minced beef with pork were detected. PMID- 22059713 TI - Growth modelling of the predominant microbial groups in hamburgers in relation to the modulation of atmosphere composition, storage temperature, and diameter of meat particle. AB - The gas composition, storage temperature, and diameter of meat particles in modified-atmosphere-packaged hamburgers were modulated according to a Central Composite Design with the aim of assessing the effects of these variables and their interaction on the predominant spoilage microbial groups, gas atmosphere and colour modifications. The parameters of the growth curves, analyzed according to the Gompertz equation, as well as the rate of gas composition and colour modification, were analyzed in order to obtain polynomial equations. The model obtained emphasized the role attributable to a structural variable such as the diameter of particles and to its interaction with atmosphere composition and temperature. Brochothrix thermosphacta was the organism endowed with the highest growth potential in the three-dimensional space defined by the range of the variables taken into consideration. The iso-response surfaces obtained and a comparison of the responses of the various groups permit the identification of the conditions able to reduce the growth of potentially hazardous micro organisms. PMID- 22059714 TI - Competitiveness across the life span: the feisty fifties. AB - Existing theories on life span changes in confidence or motivation suggest that individuals' preferences to enter competitive situations should gradually decline with age. We examined competitive preferences in a field experiment using real financial stakes in 25- to 75-year-olds (N = 543). The critical dependent variable was whether participants chose to perform a simple mental arithmetic task either under a piece-rate payment schedule (i.e., $.25 per solved item) or a competitive payment schedule ($.50 per solved item if the overall score is better than that of a randomly selected opponent, $0 otherwise). Results revealed that competitive preferences increased across the life span until they peaked around age 50, and dropped thereafter. We also found that throughout, men had a substantially larger preference for competing than women-extending previous findings on college-aged participants. The age/gender differences in preferences were neither accounted for by actual differences in performance nor individuals' subjective confidence. This first systematic attempt to characterize age differences in competitive behavior suggests that a simple decline conception of competitiveness needs to be reconsidered. PMID- 22059715 TI - Managing daily life with age-related sensory loss: cognitive resources gain in importance. AB - This paper investigates the role of cognitive resources in everyday functioning, comparing visually impaired, hearing impaired, and sensory unimpaired older adults. According to arguments that cognitive resources are of increased importance and a greater awareness of cognitive restrictions exists among sensory impaired individuals, in particular among visually impaired individuals, we hypothesized differential relationships between resources and outcomes when comparing sensory impaired and sensory unimpaired older adults. Findings are based on samples of 121 visually impaired, 116 hearing impaired, and 150 sensory unimpaired older adults (M = 82 years). Results from a sample of 43 dual sensory impaired older adults are reported for comparison. Assessment relied on established instruments (e.g., WAIS-R, ADL/IADL). Structural equation modeling showed that cognitive resources and behavior-related everyday functioning were more strongly related in the sensory impaired groups as compared to the sensory unimpaired group. Cognitive resources and evaluation of everyday functioning were significantly linked only among the sensory impaired groups. When medical condition was controlled for, these effects persisted. It is concluded that both cognitive training as well as psychosocial support may serve as important additions to classic vision and hearing loss rehabilitation. PMID- 22059716 TI - Luminance affects age-related deficits in object detection: implications for computerized psychological assessments. AB - As psychological instruments are converted for administration on computers, differences in luminance and contrast of these displays may affect performance. Specifically, high-luminance assessments may mask age-group differences that are apparent under lower luminance conditions. We examined the effects of luminance and contrast on object detection using computerized and naturalistic assessments. Younger and older adults displayed more differences in performance across differing contrast levels in conditions that were matched for luminance, despite the conditions appearing perceptually different. These findings indicate that computerized assessments should be created with luminance levels that are similar to those of the tasks they purport to simulate in order to enhance their validity. PMID- 22059717 TI - Interstitial granulomatous dermatitis: a distinct entity with characteristic histological and clinical pattern. AB - BACKGROUND: Interstitial granulomatous dermatitis (IGD) is a rare disease for which a clinical-pathological correlation is essential to establish diagnosis. OBJECTIVES: To describe the histological and clinical features of patients with IGD seen in our department from 2004 to 2010, and to undertake a literature review and critical analysis of additional cases. METHODS: Twelve adult patients (nine women and three men; mean age 58.5 years; range 32-73 years) with IGD were enrolled. Lesions consisted of asymptomatic erythematous papules and plaques, symmetrically distributed on the trunk and the proximal limbs. Two patients had skin-coloured papules. Six patients had articular involvement (arthralgias, spondyloarthritis, rheumatoid arthritis) and three patients had cancer. RESULTS: All cases showed a predominant CD68-positive macrophage infiltrate distributed between collagen bundles of the mid- and deep dermis. Macrophages were also surrounding degenerated collagen fibres. A few neutrophils and/or eosinophils were also present. No vasculitis or significant mucin deposition was observed. Of the 62 cases of IGD reported since 1993, 53 fulfilled stringent diagnostic criteria. Erythematous papules and plaques on the trunk and proximal limbs were the dominant manifestation. Approximately 10% of patients had cord-like lesions. More than 50% of patients with IGD had arthralgia or arthritis, and less commonly other rheumatic disorders. Disease duration is months to years, but long-term prognosis seems favourable. CONCLUSIONS: IGD is a distinct entity with a typical histological and clinical pattern. The importance and the nature of the association with extracutaneous diseases remains to be clarified. Patients should be screened for rheumatic and autoimmune diseases. PMID- 22059718 TI - Modeling the mechanism of the glutathione peroxidase mimic ebselen. AB - Ebselen (1), the quintessential mimic of the antioxidant selenoenzyme glutathione peroxidase (GPx), is a potential chemopreventative for various diseases associated with oxidative stress. Density-functional theory (DFT) and solvent assisted proton exchange (SAPE) are used to model the complex mechanism for scavenging of reactive oxygen species by 1. SAPE is a microsolvation method designed to approximate the role of bulk solvent in chemical processes involving proton transfer. Consistent with experimental studies, SAPE studies predict the reaction of 1 with thiol (RSH) to form a selenenyl sulfide 2 to be preferred under most conditions, with an alternate pathway through a selenoxide 3 possible at high reactive oxygen species (ROS) concentrations ([ROS] ? [RSH]). The reduction of 2 to the selenol 4, known to be rate-determining in the protein, has a high SAPE activation barrier due to a strong Se...O interaction which reduces the electrophilicity of the sulfur center of the -SeS- bond of 2. Thiols, such as dithiols and peptide-based thiols, are expected to overcome this barrier through structural features that increase the probability of attack at this sulfur. Thus, in vivo, the GPx-like pathway is the most likely mechanism for 1 under most circumstances, except, perhaps, under extreme oxidative stress where initial oxidation to 3 could compete with formation of 2. Simple thiols, used in various in vitro studies, are predicted by SAPE modeling to proceed through oxidation of 2 to a seleninyl sulfide intermediate. Overall, SAPE modeling provides a realistic interpretation of the redox mechanism of 1 and holds promise for further exploration of complex aqueous-phase reaction mechanisms. PMID- 22059719 TI - Evaluation of non-contact infrared thermometry for measuring the temperature of pig carcasses in chillers. AB - An OPTEX Thermo Hunter infrared (IR) non-contact hand-held thermometer was examined to determine its suitability for measuring porcine carcass surface temperatures during chilling. The manufacturer claims that the unit has the capability of measuring a range of temperature between -50 degrees C and 500 degrees C, with a resolution of 0.1 degrees C. The device allows for an automatic determination and adjustment of unknown emissivities of objects to be measured. The stability of the device was tested in the laboratory at 4 and 18 degrees C and for accuracy against a known surface temperature. Tests were conducted in a commercial chiller to determined whether the device could detect temperature differences between carcasses, sites on one carcass and chillers. The results obtained were also examined for repeatability. The thermometer required a minimum initial stabilisation period of 120 min after which the results compared favourably with known surface temperatures. The chiller tests indicated that temperature differences could be detected between the various carcasses, sites on one carcass and chillers, and that the readings were reproducible. The device is best suited for determining temperature trends when overall accuracy is not essential. The device could also be useful in evaluating chiller performance. PMID- 22059720 TI - The influence of different centralised pre-packaging systems on the shelf-life of fresh pork. AB - The influence of different centralised pre-packaging systems (PVC, modified atmosphere packaging (MAP), 25% CO(2) and 75% O(2), vacuum skin packaging (VSP) and the mother bag concept, 100% CO(2)) on the shelf-life (0, 7, 14 and 21 days at 0 degrees C) of fresh pork was determined using microbiological, colour, odour and acceptability characteristics. All the packaging treatments were equally efficient for the first 4 days of retail display. In the extended shelf-life study (7, 14 and 21 days) the mother bag centralised packaging system gave the most promising shelf-life results (21 days) and was also judged superior in terms of odour. Modified atmosphere packaging (14 days) and VSP (7 days) may be considered as other possible options. PMID- 22059721 TI - The influence of additives on the oxidation of pork back fat and its effect on water and fat binding in finely comminuted batters. AB - We have found in previous experiments that slaughter-fresh processed pork back fat enhances batter stability in frankfurter-type sausages. In an attempt to clarify whether the decrease of batter stability with storage time of the fatty tissue is due to the fat oxidation a series of experiments was conducted using sodium nitrite and nitrate, 6- O -palmitoyl- l -ascorbic acid and dl-ga tocopherol as additives to the fatty tissue. It was found that sodium nitrite and nitrate, although the first is regarded as an antioxidant in meat, had a pro oxidant effect when added to the fatty tissue. The palmitoyl-l-ascorbic acid showed the best antioxidative activity, and the dl-alpha-tocopherol was less effective as an antioxidant. Contrary to its effect on the increase in fat oxidation, sodium nitrite addition gave a remarkable improvement in batter stability, expressed as jelly and fat separation, which was more pronounced on the second day of storage of the fatty tissue. The pro-oxidant effect of nitrite increased up to a concentration of 375 ppm added to the fatty tissue. Concentrations of nitrite in fatty tissue up to 125 ppm had no influence on jelly release but at higher concentrations the jelly separation decreased. All nitrite concentrations, from 62.5 to 2250 ppm, showed significantly lower fat separation than for the control treatment, especially on the eighth and 15th day of storage of the fatty tissue. The results show that fat oxidation has little effect on batter stability. Further experiments are needed to clarify the mode of action of nitrite in improving batter stability. PMID- 22059722 TI - Thermal scanning rheology of myofibrillar proteins from muscles of defined fibre type. AB - Emulsion meat products are made with little regard to rheological properties of different muscles. Here the rheology of gels made from three classes of muscle defined by myosin type (fast twitch, slow twitch and heart) are compared. Myofibrillar fractions were prepared from representative bovine muscles-cutaneus trunci, masseter and heart-by a procedure that removed connective tissue, fat and sarcoplasmic proteins. Complicating effects of nongelling agents were thus minimized. Fractions were mixed with NaCl and pyrophosphate at concentrations typical of those used in processed meats. Rigidity and elasticity of the gelling mixtures were monitored during heating from 10 to 84 degrees C over a range of pH values. Several indices of gelation showed that masseter and heart (slow muscle group) gelations were similar to each other but distinct from cutaneus trunci (fast) gelation. Gelation temperature was 10 degrees C lower for fast than slow, perhaps explainable by one of two hypotheses: differential salt extraction or lower thermal stability of fast myosin rod. Cutaneus trunci gels were also more rigid at all pH values. Slow group gels suffered from proteolysis, which was combated with cathepsin inhibitors. For both fast and slow groups, rigidity increased as pH decreased, analogous to results reported for purified myosin in dilute solution. Texture also changed. Below pH 5.7 slow group gels were brittle and granular, with low water-holding capacity. Above that pH, gels were elastic and smooth. The equivalent point for cutaneus trunci gels was pH 5.5. Around pH 7, pyrophosphate had a fluidizing effect at pregelation temperatures, but elasticity data indicated that this ion plays no part in final gelation. PMID- 22059723 TI - The influence of pre-slaughter oral loading of acid or base on post-mortem changes in Longissimus Dorsi muscle of pork. AB - Twenty-four pigs were assigned to one of four ad libitum water treatments: control, sodium bicarbonate (12.6 g/litre), low ammonium chloride (4 g/litre) or high ammonium chloride (8 g/litre) for 5 days, to study the influence of an oral acid or base load on post-mortem changes in longissimus dorsi muscle and ultimate pork quality. Physiological changes before slaughter were monitored by measuring blood pH, pCO(2) and HCO(3)(-). The influence of dietary treatments on post mortem changes and ultimate meat quality was determined by measuring glycolytic enzymes and intermediates, and muscle pH, color and water-holding capacity (WHC). As expected, sodium bicarbonate generated a metabolic alkalosis, whereas ammonium chloride resulted in a metabolic acidosis. Pre-slaughter acid-base status was positively correlated with muscle WHC (P < 0.05). However, no significant dietary treatment effect was observed in muscle quality traits such as color (a, b, L) and WHC. Muscle pH(45) was significantly (P < 0.05) higher in bicarbonate than control and high ammonium chloride treatments. The activity of Ca(2+)-dependent protein kinase was significantly (P < 0.05) higher at 45 min post-mortem but that of pyruvate kinase was significantly lower at 2 and 4 h post mortem in bicarbonate-treated pigs. At 45 min post mortem, the activity of fructose-1,6 diphosphatase in the control pigs was significantly higher (P < 0.05) than on other treatments. The concentration of glycogen was significantly (P < 0.05) higher in bicarbonate and high ammonium chloride pigs; bicarbonate-treated pigs also has significantly higher adenosine-5'-triphosphate (ATP) and pH values than other treatment groups (P < 0.05) at early post-mortem. It was concluded that pre slaughter oral loading of acid or base could induce changes in muscle metabolism and post-mortem muscle pH. Further research is required to confirm that altering diet acidogenicity or alkalinogenicity may be a means of enhancing ultimate pork quality. PMID- 22059724 TI - The variation in pig muscle glycolytic potential during lairage-an in-vivo study. AB - The variations in glycolytic potential (GP, very close to glycogen content) were studied during lairage in pig m. longissimus dorsi using biopsy sampling. Pigs were sampled on arrival at the abattoor and after treatment. Post-mortem measurements including pH(1), pH(u) and FOP(u) were performed on both longissimus dorsi (LD) and biceps femoris (BF) muscles. The animals underwent one of the following treatments: 2 h lairage mixed or unmixed; 24 h lairage mixed or unmixed with access to water only; 24 h lairage mixed or unmixed with access to a sugar solution. A significant depletion in GP occurred during lairage except when pigs were fed liquid sugar. The extent of this depletion was irrespective of lairage duration or mixing. Pigs lairaged 24 h with access to water only exhibited a significantly lower pH(1) in m. BF suggesting a higher propensity to develop PSE meat. Values of pH(u) were low (pH < 5.5), and did not vary significantly between the treatments since muscle GP remained high, despite the depletion induced by lairage. This was attributed to the high level of muscle glycogen characterizing the Hampshire crossbred pigs used in this experiment. These results suggest that interaction between breed and handling procedure may be important regarding meat pH(u). PMID- 22059725 TI - The use of proteases from extreme thermophiles for meat tenderisation. AB - The potential use of the thermophile enzymes E A.1 protease (from Bacillus strain E A.1), 4-1.A protease (from Thermus strain Rt4-1.A) and caldolysin (from Thermus strain T-351) in meat tenderisation has been investigated. Temperature-activity relationships illustrated that E A.1 and 4-1.A proteases were more active on collagen than on meat powder at cooking temperatures (70-90 degrees C), whereas caldoysin was more active on meat powder. The potential of E A.1 and 4-1.A proteases was therefore investigated further using sensory and mechanical evaluation. An Instron Universal Testing Machine was used to quantitatively investigate the effect of cooking temperature and protease concentration on homogenised meat patties. With a cooking time of 30 min, the best protease concentrations (of those used) were found to be 0.75 U/g meat for E A.1 protease and 1.5 U/g meat for 4-1.A protease. The optimum cooking temperature was 80 degrees C in both cases. Sensory analysis confirmed that these concentrations (and also 0.38 U/g meat for E A.1 protease) improved the tenderness significantly. At high concentrations the proteases had a detrimental effect on the mouthfeel of the patties. At lower concentrations this effect was less marked, and good tenderisation was obtained. PMID- 22059726 TI - Lipid composition of adipose tissue and muscle in pigs with an increasing proportion of Meishan genes. AB - The purpose of this study was to estimate the effect of the proportion of Meishan (MS) genes upon the lipid composition of longissimus dorsi and trapezius muscles and perirenal and s.c. dorsal adipose tissues. Five groups of 11-15 pigs with 0, 12.5, 25, 37.5 and 50% MS genes were made up from a large herd of crossbred animals (0-100% MS dams * Pietrain sires). Results showed that: (1) the i.m. lipid content was higher in 1 2 MS than in controls and 1 4 MS pigs. Differences in the fatty acid composition of i.m. lipids, as related to genotype, depended more particularly on muscle fatness as the fatty acid compositions of triglycerides and phospholipids were little affected by the genotype. (2) The weight of perirenal and s.c. dorsal adipose tissues increased with the proportion of MS genes. Differences in the chemical composition of the adipose tissues were not related to the proportion of MS genes. The fatty acid composition was little affected by the genotype. Although the levels of polyunsaturated fatty acids decreased with increasing proportion of MS genes, these small variations had no marked influence on adipose tissue quality. PMID- 22059727 TI - Protein C, protein S and von Willebrand factor levels correlate with bleeding symptoms: a population-based study. AB - Although natural anticoagulant deficiencies are the established causes of thrombosis, their roles in bleeding are not fully studied. The objective is to correlate haemostatic factors with haemorrhagic symptoms quantified by a standardized questionnaire. Adult subjects were recruited from Bangkok and nearby provinces as part of routine health surveys/checkups. The validated MCMDM-1VWD form was used to assess their bleeding symptoms. At the same time, von Willebrand factor (VWF) activity, free protein S levels and protein C activity were measured. There were 5196 individuals. The mean age was 44.3 years (range 15-99) and 41% were male subjects. The mean bleeding score was -0.28 and 95% of subjects had scores between -2 and +2. The scores were lower in female subjects than in male subjects (-0.35 vs. -0.16, P < 0.001). Bleeding scores correlated negatively with age, VWF and protein C activities (Spearman's rho-0.258, -0.091 and -0.098, respectively, all P < 0.001), but did not significantly correlate with protein S levels. Using multivariate analysis, female gender, VWF below 100 IU dL(-1), protein C below 100 IU dL(-1) and protein S over 150 IU dL(-1) significantly related to high (>=3) bleeding scores (adjusted odds ratio 1.95, 1.83, 1.56 and 2.84, P = 0.001, 0.001, 0.039 and 0.017, respectively). These findings may suggest interacting roles of VWF and natural anticoagulants in modifying bleeding symptoms. PMID- 22059728 TI - cAMP-CRP co-ordinates the expression of the protein acetylation pathway with central metabolism in Escherichia coli. AB - Lysine acetylation is a well-established post-translational modification widely conserved and distributed in bacteria. Although multiple regulatory roles have been proved, little is known about its regulation. Here, we present evidence that the transcription of the Gcn5-like acetyltransferase YfiQ of Escherichia coli (proposed name: PatZ) is regulated by cAMP-CRP and its implications on acetate metabolism regulation. The acetate scavenging acetyl-CoA synthetase (Acs) is regulated at the transcriptional and post-translational levels. Post translational regulation depends on a protein acetyltransferase (yfiQ) and an NAD(+) -dependent deacetylase (cobB). We have studied their expression under different environmental conditions. cobB is constitutively expressed from a promoter located upstream nagK. The expression of yfiQ occurs from its own promoter; it is upregulated in the stationary phase and in the presence of non PTS carbon sources and is positively regulated by cAMP-CRP. Two putative CRP binding sites are necessary for its full activity. Gene deletion revealed that cobB is essential for growth on acetate, yfiQ deletion restoring growth of the cobB mutant. The fine tuning of metabolic enzymes results from the integration of multiple mechanisms, and redundant systems may exist. Despite the existence of divergent catabolite repression systems, this may be a conserved strategy common to both Gram-positive and -negative bacteria. PMID- 22059729 TI - Esperanza y Vida: a culturally and linguistically customized breast and cervical education program for diverse Latinas at three different United States sites. AB - Breast cancer is the most common cause of cancer and the leading cause of cancer death among Latinas in the United States. In addition, Latinas experience a disproportionate burden of cervical cancer incidence, morbidity, and mortality compared with non-Hispanic White women. Lower use of breast and cervical cancer screening services may contribute to these disparities. To address the underutilization of breast and cervical cancer screening among diverse subgroups of Latinas, a peer-led education program called Esperanza y Vida ("Hope and Life") was developed and administered at 3 sites (2 in New York and 1 in Arkansas). Immigrant Latina women and their partners were educated about the importance of breast and cervical cancer screening, with the goals of increasing their knowledge about these cancers and their screening behavior. An analysis of the intervention's findings at baseline among female participants demonstrated significant sociodemographic, interpersonal, cultural, health care system, and program variability in 3 distinct geographic regions in the United States. These data indicate the need for and feasibility of customizing cancer outreach and educational programs for diverse Latina subgroups living in various U.S. regions, with implications for informing the expansion and replication of the program in other regions of the country. PMID- 22059730 TI - Ablation catheter entrapment by chordae tendineae in the mitral valve during ventricular tachycardia ablation. AB - We report on the entrapment of an ablation catheter by chordae tendineae in the mitral valve during radiofrequency (RF) ablation of ventricular tachycardia. The entrapped tip had to be removed via open surgery. Great care must be taken when performing radiofrequency ablation around the mitral valve apparatus. PMID- 22059731 TI - Examining structural and clinical factors associated with implementation of standing orders for adult immunization. AB - A proven method to increase vaccination rates in primary care is a standing orders program (SOP) for nonphysician staff to assess and vaccinate eligible individuals without a specific written physician order. This study describes a mixed methods approach to examining physicians' beliefs and attitudes about and adoption of SOPs for adult immunizations, specifically, influenza and pneumococcal polysaccharide vaccine. Focus groups and in-depth interviews of physicians, nurses, practice managers, and the medical director of a managed care health plan were conducted. Results were used to enrich a concise survey based on the Awareness-to-Adherence model of physician behavior and previous research, which was mailed to 1,640 general internists and family physicians nationwide. Barriers to SOPs identified through qualitative methods were lack of interest in changing the status quo, a physician-dominated hierarchy, and fear of malpractice. Facilitators included having an electronic medical record and a practice culture that was open to change. The survey (response rate 67%) confirmed the facilitators and further identified patient, physician, and practice factors that served as barriers to establishing and maintaining SOPs. This mixed methods approach provided the opportunity to develop a tailored and practice-oriented survey for examining the contextual factors influencing clinical providers' decisions to implement SOPs for adult immunization. PMID- 22059732 TI - The influence of story context on a working memory span task. AB - The purpose of the present study was to examine factors that could influence whether recall performance in the reading span task (Daneman & Carpenter, 1980 ) would benefit from the contextual information from the sentences in the processing component of the task. More specifically, we investigated whether people would benefit from sentence sets that formed short stories or when the entire span task was one continuous story. Overall, there was a clear benefit for contextually related sentence sets (i.e., the story span tasks) compared to the traditional reading span task. However, the benefit was eliminated when the entire set formed one continuous story. These results support the recall reconstruction hypothesis for working memory (Towse, Cowan, Hitch, & Horton, 2008 ), which suggests that people may strategically use the content of the sentences from the processing component of the reading span task as memorial cues to reconstruct the target words of the storage component. However, this benefit is constrained to scenarios when the contextual cues are unique to a specific set. PMID- 22059733 TI - Template-free synthesis and encapsulation technique for layer-by-layer polymer nanocarrier fabrication. AB - The encapsulation of therapeutic molecules within multiple layers of biocompatible and biodegradable polymeric excipients allows exquisite design of their release profile, to the extent the drug can be selectively delivered to a specific target location in vivo. Here, we develop a novel technique for the assembly of multilayer polyelectrolyte nanocarriers based on surface acoustic wave atomization as a rapid and efficient alternative to conventional layer-by layer assembly, which requires the use of a sacrificial colloidal template over which consecutive polyelectrolyte layers are deposited. Polymer nanocarriers are synthesized by atomizing a polymer solution and suspending them within a complementary polymer solution of opposite charge subsequent to their solidification in-flight as the solvent evaporates; reatomizing this suspension produces nanocarriers with a layer of the second polymer deposited over the initial polymer core. Successive atomization-suspension layering steps can then be repeated to produce as many additional layers as desired. Specifically, we synthesize nanocarriers comprising two and three, and up to eight, alternating layers of chitosan (or polyethyleneimine) and carboxymethyl cellulose within which plasmid DNA is encapsulated and show in vitro DNA release profiles over several days. Evidence that the plasmid's viability is preserved and hence the potential of the technique for gene delivery is illustrated through efficient in vitro transfection of the encapsulated plasmid in human mesenchymal progenitor and COS-7 cells. PMID- 22059734 TI - Design, measures and sample characteristics of the CadeViMa-Spain survey on quality of life in community-dwelling older adults. AB - BACKGROUND: The survey "Quality of life in older adults-Spain" (CadeViMa-Spain) was designed to obtain information about objective and subjective determinants of Quality of Life (QoL) in old age, from a multidimensional perspective. This paper presents the overall description, methodology, sample characteristics and reliability of the measures used. METHODS: A cross-sectional survey was carried out in a representative sample of 1106 community-dwelling adults aged 60 years and over in Spain. The sample was obtained by a geodemographically-based proportional multistage stratified sampling. A home-based questionnaire included validated scales and questions about sociodemographic characteristics, global QoL, health, family and social networks, financial means and retirement, leisure and social participation, residential environment, and satisfaction with those issues. Face-to-face semi-structured interviews were conducted. Cronbach's alpha coefficients were used to assess internal consistency of the scales. RESULTS: This nationally representative survey furnishes information about global QoL, health-related QoL, resources availability, living conditions, and satisfaction with the assessed aspects, including life domains most valued by this group. In general, community-dwelling older adults reported positive assessments of health, living conditions, and high levels of satisfaction with the different aspects of QoL. The reliability of the measures in this population was good. CONCLUSIONS: This survey provides comprehensive and useful information, based on the view of older people themselves, with potential to contribute to health and social policies towards promoting active aging. The database is available for in-depth comparisons. PMID- 22059735 TI - Synchronous fluorescence spectrofluorimetric method for the simultaneous determination of metoprolol and felodipine in combined pharmaceutical preparation. AB - A rapid, simple and sensitive synchronous specrtofluorimetric method has been developed for the simultaneous analysis of binary mixture of metoprolol (MTP) and felodipine (FDP). The method is based upon measurement of the synchronous fluorescence intensity of the two drugs at Deltalambda of 70 nm in aqueous solution. The different experimental parameters affecting the synchronous fluorescence intensities of the two drugs were carefully studied and optimized. The fluorescence intensity-concentration plots were rectilinear over the ranges of 0.5-10 MUg/mL and 0.2-2 MUg/mL for MTP and FDP, respectively. The limits of detection were 0.11 and 0.02 MUg/mL and quantification limits were 0.32 and 0.06 MUg/mL for MTP and FDP, respectively. The proposed method was successfully applied for the determination of the two compounds in their commercial tablets and the results obtained were favorably compared to those obtained with a comparison method. PMID- 22059736 TI - Initial therapy with the fixed-dose combination of sitagliptin and metformin results in greater improvement in glycaemic control compared with pioglitazone monotherapy in patients with type 2 diabetes. AB - AIMS: To evaluate the efficacy and safety of initial therapy with a fixed-dose combination (FDC) of sitagliptin and metformin compared with pioglitazone in drug naIve patients with type 2 diabetes. METHODS: After a 2-week single-blind placebo run-in period, patients with type 2 diabetes, HbA1c of 7.5-12% and not on antihyperglycaemic agent therapy were randomized in a double-blind manner to initial treatment with a FDC of sitagliptin/metformin 50/500 mg twice daily (N = 261) or pioglitazone 30 mg per day (N = 256). Sitagliptin/metformin and pioglitazone were up-titrated over 4 weeks to doses of 50/1000 mg twice daily and 45 mg per day, respectively. Both treatments were then continued for an additional 28 weeks. RESULTS: From a mean baseline HbA1c of 8.9% in both groups, least squares (LS) mean changes in HbA1c at week 32 were -1.9 and -1.4% for sitagliptin/metformin and pioglitazone, respectively (between-group difference = 0.5%; p < 0.001). A greater proportion of patients had an HbA1c of <7% at week 32 with sitagliptin/metformin vs. pioglitazone (57% vs. 43%, p < 0.001). Compared with pioglitazone, sitagliptin/metformin treatment resulted in greater LS mean reductions in fasting plasma glucose (FPG) [-56.0 mg/dl (-3.11 mmol/l) vs. -44.0 mg/dl (-2.45 mmol/l), p < 0.001] and in 2-h post-meal glucose [-102.2 mg/dl ( 5.68 mmol/l) vs. -82.0 mg/dl (-4.56 mmol/l), p < 0.001] at week 32. A substantially greater reduction in FPG [-40.5 mg/dl (-2.25 mmol/l) vs. -13.0 mg/dl (-0.72 mmol/l), p < 0.001] was observed at week 1 with sitagliptin/metformin vs. pioglitazone. A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of beta-cell function (HOMA-beta) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin. Both sitagliptin/metformin and pioglitazone were generally well tolerated. Sitagliptin/metformin led to weight loss (-1.4 kg), while pioglitazone led to weight gain (3.0 kg) (p < 0.001 for the between-group difference). Higher incidences of diarrhoea (15.3% vs. 4.3%, p < 0.001), nausea (4.6% vs. 1.2%, p = 0.02) and vomiting (1.9% vs. 0.0%, p = 0.026), and a lower incidence of oedema (1.1% vs. 7.0%, p < 0.001), were observed with sitagliptin/metformin vs. pioglitazone. The between-group difference in the incidence of hypoglycaemia did not reach statistical significance (8.4 and 4.3% with sitagliptin/metformin and pioglitazone, respectively; p = 0.055). CONCLUSION: Compared with pioglitazone, initial therapy with a FDC of sitagliptin and metformin led to significantly greater improvement in glycaemic control as well as a higher incidence of prespecified gastrointestinal adverse events, a lower incidence of oedema and weight loss vs. weight gain. PMID- 22059738 TI - Protein conjugated with aldehydes derived from lipid peroxidation as an independent parameter of the carbonyl stress in the kidney damage. AB - BACKGROUND: One of the well-defined and characterized protein modifications usually produced by oxidation is carbonylation, an irreversible non-enzymatic modification of proteins. However, carbonyl groups can be introduced into proteins by non-oxidative mechanisms. Reactive carbonyl compounds have been observed to have increased in patients with renal failure. In the present work we have described a procedure designed as aldehyde capture to calculate the protein carbonyl stress derived solely from lipid peroxidation. METHODS: Acrolein-albumin adduct was prepared as standard at alkaline pH. Rat liver microsomal membranes and serum samples from patients with diabetic nephropathy were subjected to the aldehyde capture procedure and aldol-protein formation. Before alkalinization and incubation, samples were precipitated and redisolved in 6M guanidine. The absorbances of the samples were read with a spectrophotometer at 266 nm against a blank of guanidine. RESULTS: Evidence showed abundance of unsaturated aldehydes derived from lipid peroxidation in rat liver microsomal membranes and in the serum of diabetic patients with advanced chronic kidney disease. Carbonyl protein and aldol-proteins resulted higher in the diabetic nephropathy patients (p < 0.004 and p < 0.0001 respectively). CONCLUSION: The aldehyde-protein adduct represents a non oxidative component of carbonyl stress, independent of the direct amino acid oxidation and could constitute a practical and novelty strategy to measure the carbonyl stress derived solely from lipid peroxidation and particularly in diabetic nephropathy patients. In addition, we are in a position to propose an alternative explanation of why alkalinization of urine attenuates rhabdomyolysis-induced renal dysfunction. PMID- 22059739 TI - Concomitant endoureterotomy and dextranomer/hyaluronic acid subureteral injection for management of obstructive refluxing megaureter. AB - PURPOSE: To present the results of our experience with combined endoureterotomy and endoscopic injection of dextranomer/hyaluronic acid (Deflux) for the treatment of primary obstructive refluxing megaureter (PORM). PATIENTS AND METHODS: Eighteen children (12 female, 6 male; mean age-14 months) with 20 PORM units underwent concomitant endoureterotomy and endoscopic subureteral Deflux injection. All patients underwent endoureterotomy at the 6-o'clock position with insertion of a 3F Double-J ureteral stent into the obstructed segment of ureter and subureteral injection of Deflux at the 5-o'clock and 7-o'clock positions. The Double-J stent was left in place with its distal tip fixed with a single knot to the external genitalia for easy removal after 1 week. Patients with refluxing nonobstructive ureter on the contralateral side of the PORM unit (seven children) underwent simultaneous endoscopic subureteral injection of Deflux. Voiding cystourethrography (VCUG) was performed at 6 months, and ultrasonography was performed at 1 week 3, 6, and 12 months postoperatively. RESULTS: With a mean follow-up of 30 months, the procedure was uneventful in all patients. Follow-up VCUG showed no evidence of reflux in 15 ureterorenal (75%), significant decrease in reflux grade in 2 (10%), and no change in 3 (15%) in the endoscopic treated PORM units. No evidence of reflux was observed in the treated contralateral refluxing nonobstructive ureters. Ultrasonography revealed no ureterovesical junction obstruction. In 19 ureterorenal (95%) units, there was a complete resolution or decrease in hydroureteronephrosis. CONCLUSIONS: The results of this study demonstrate that combined endoureterotomy and subureteral injection of Deflux is safe and effective in the treatment of PORM in selected patients. PMID- 22059740 TI - Evidence of clinical competence. AB - This cross-sectional research used a qualitative questionnaire to explore clinical competence in nursing. The aim was to look for evidence of how clinical competence showed itself in practice. In the research, the views from both education and working life are combined to broadly explore and describe clinical competence from the perspective of students, clinical preceptors and teachers. The questions were formulated on how clinical competence is characterised and experienced, what contributes to it and how it is maintained, and on the relation between clinical competence and evidence-based care. The answers were analysed by inductive content analysis. The results showed that clinical competence in practice is encountering, knowing, performing, maturing and improving. Clinical competence is an ongoing process, rather than a state and manifests itself in an ontological and a contextual dimension. PMID- 22059741 TI - MicroRNA-1 induces apoptosis by targeting prothymosin alpha in nasopharyngeal carcinoma cells. AB - BACKGROUND: MiR-1 (microRNA-1) has been used as a positive control in some microRNA experiments. We found that miR-1 transfection of nasopharyngeal carcinoma cells reveals a typical apoptotic process as shown by time-lapse microscopy so we investigated the mechanisms of miR-1 inducing apoptosis. METHODS: To confirm that miR-1 induces apoptosis, we used Annexin V and TUNEL staining and caspase assay. To determine that miR-1 directly targets genes that involve in apoptosis, we analyzed microRNA and pathway databases, and cDNA expression microarrays from miR-1 transfected cells. To demonstrate candidate miR 1 targeted genes, we used qRT-PCR analysis and luciferase reporter vector assays. To assess the miR-1 target gene PTMA (prothymosin alpha, ProTalpha) involves in apoptosis, we used PTMA siRNA to knock down PTMA. RESULTS: Annexin V and TUNEL staining and caspase assay confirm that miR-1 induces nasopharyngeal carcinoma cell apoptosis. MiR-1 transfection of HeLa, Cal-27, KYSE30 and NPC-TW06 cell lines which express low levels of endogenous miR-1 also induces apoptosis. However, miR-1 transfection of cell lines such as SW620, HepG2, HEK-293T, SAS and PC-13 which express high levels of endogenous miR-1 does not result in apoptosis. MiR-1 directly targets PTMA gene. PTMA siRNA and miR-1 accelerate the apoptotic process in cells treated with apoptosis inducers. CONCLUSIONS: The exogenous expression of miR-1 induces apoptosis in a number of cell lines. This is a model of microRNA-induced cell apoptosis. The PTMA is one of miR-1 target genes which involve in miR-1 inducing apoptosis. The apoptotic inducers including actinomycin D, camptothecin and etoposide are also the chemotherapeutic drugs in clinical cancer therapy and PTMA siRNA can accelerate apoptotic progression in cells treated with those apoptosis inducers. Therefore PTMA siRNA may have potential applications as an adjuvant in cancer chemotherapy. PMID- 22059742 TI - Ni(COD)2/PCy3 catalyzed cross-coupling of aryl and heteroaryl neopentylglycolboronates with aryl and heteroaryl mesylates and sulfamates in THF at room temperature. AB - Reaction conditions for the Ni(COD)(2)/PCy(3) catalyzed cross-coupling of aryl neopentylglycolboronates with aryl mesylates were developed. By using optimized reaction conditions, Ni(COD)(2)/PCy(3) was shown to be a versatile catalyst for the cross-coupling of a diversity of aryl neopentylglycolboronates with aryl and heteroaryl mesylates and sulfamates containing both electron-donating and electron-withdrawing substituents in their para, ortho, and meta positions in THF at room temperature. This Ni-catalyzed cross-coupling of aryl neopentylglycolboronates is also effective for the synthesis of heterobiaryls and biaryls containing electrophilic functionalities sensitive to organolithium and organomagnesium derivatives. In combination with the recently developed Ni catalyzed neopentylglycolborylation, all Ni-catalyzed routes to functional biaryls and heterobiaryls are now easily accessible. PMID- 22059743 TI - Friction and adhesion forces of Bacillus thuringiensis spores on planar surfaces in atmospheric systems. AB - The kinetic friction force and the adhesion force of Bacillus thuringiensis spores on planar surfaces in atmospheric systems were studied using atomic force microscopy. The influence of relative humidity (RH) on these forces varied for different surface properties including hydrophobicity, roughness, and surface charge. The friction force of the spore was greater on a rougher surface than on mica, which is atomically flat. As RH increases, the friction force of the spores decreases on mica whereas it increases on rough surfaces. The influence of RH on the interaction forces between hydrophobic surfaces is not as strong as for hydrophilic surfaces. The friction force of the spore is linear to the sum of the adhesion force and normal load on the hydrophobic surface. The poorly defined surface structure of the spore and the adsorption of contaminants from the surrounding atmosphere are believed to cause a discrepancy between the calculated and measured adhesion forces. PMID- 22059744 TI - Radiation therapy in the management of unilesional primary cutaneous T-cell lymphomas. PMID- 22059745 TI - A technique for muscle biopsy sampling on pigs to assess intramuscular fat. AB - The objective of the research was to develop a rapid, convenient method for sampling the muscle of live young pigs. A biopsy needle has been developed. It consists of two parts, a hollow outer cylinder and an inner stick. From female piglets (10-25 kg) a biopsy sample of 108 +/- 42 mg was taken from the biceps femoris. No infections or mobility problems were observed. The sample can be used for further i.m. fat analysis. The mean fat content in the biceps femoris is 2.24 +/- 1.12%. This i.m. fat content was measured by extraction in a Soxhlet apparatus and was determined by a Fourier transform Infrared (FTIR) method. Fatty acid composition was determined by gas-liquid chromatography. PMID- 22059746 TI - Glycogen content, buffering capacity and resting pH in live muscles of pigs of different halothane genotypes (a pilot project). AB - The development of PSE (pale, soft and exudative) meat is characterized by a rapid decrease in pH post-mortem and/or a low ultimate pH. We investigated some physiological properties of the live muscle (the glycogen content, the non bicarbonate buffering capacity and 'resting pH'), which could influence both the decrease in pH and the ultimate pH. Measurements were performed on three halothane genotypes, hal(N)hal(N), hal(N)hal(n) and hal(n)hal(n), with their known predispositions for PSE meat. It was demonstrated that the glycogen content in both the groups of double recessive and heterozygous individuals was higher than the levels in the group of homozygous dominant pigs. No difference was found in non-bicarbonate buffering capacity between the groups. The groups with the highest glycogen levels also had the lowest 'resting pH' values. The results indicate that measurement of glycogen content in vivo may be superior to the halothane test in detecting PSE-prone individuals. The lower pH values of carriers of the hal(n) gene further indicate that the characteristic rapid decrease after slaughter may not be as fast as generally accepted, as even very low pH values can be observed in the muscles of live pigs. PMID- 22059747 TI - On the assessment of water-holding capacity of hot- vs cold-boned pork. AB - The effects of time of boning and storage period on creatine kinase (CK) activity, transmission value, drip losses and water-holding capacity (WHC) measured by various methods was investigated. At 40 min post-mortem 30 pig carcasses with pH values > 6.2 in the loin were selected. The right loin of each carcass was hot boned and vacuum packaged immediately. The left loin was cold boned and packaged after overnight chilling at 2 +/- 2 degrees C. After 1, 5 and 12 days of storage at 0 +/- 1 degrees C, 10 hot- and cold-boned loins were unpacked and sampled. Time of boning did not affect drip losses. At 1 day post mortem the CK activity was higher in hot- than in cold-boned pork. Sarcomere lengths were not affected by time of boning. The WHC was investigated by two controlled methods. A filter-paper press method was not sensitive enough to assess differences in WHC of hot- vs cold-boned pork. The results of a gravimetric method depended on the sample location. Results of the gravimetric test decreased with increasing storage periods. The results suggest that under the experimental conditions the chilling rates of hot-boned vs carcass-attached muscles were similar. PMID- 22059748 TI - The effects of ante-mortem feed and water withdrawal, ante-mortem electrolyte supplementation, and post-mortem electrical stimulation on the palatability and consumer acceptance of bull beef after ageing (6 days at 1 degrees C). AB - A total of 120 bulls each weighing approximately 500 kg were used to evaluate the effects of withholding feed and water for various intervals pre-slaughter, ante mortem supplementation with an electrolyte solution, and post-mortem electrical stimulation on the cooking and palatability attributes and consumer acceptance of boneless rib steaks aged for 6 days at 1 degrees C. The results clearly showed the detrimental effects of withholding feed and water pre-slaughter and the beneficial effects of post-mortem electrical stimulation on the eating quality of bull beef aged for 6 days at 1 degrees C. Taste panel ratings of palatability attributes between electrolyte-treated and untreated animals did not differ significantly. However, consumer evaluations indicated a lower overall palatability rating for electrolyte-treated bulls. The results clearly indicate that feed and water deprivation is detrimental to the palatability attributes and consumer acceptance of aged bull beef. PMID- 22059749 TI - Effects of ultrarapid chilling and ageing on length of sarcomeres, and tenderness of pork. AB - In this study, the m. longissimus dorsi and the m. semimembranosus of pigs with normal and accelerated glycolysis (pale, soft and exudative, PSE) were used to evaluate the effect of ultrarapid chilling methods (with short-term freezing of the muscle surface) and ageing up to 72 h post-mortem on length of sarcomeres, Warner Bratzler shear force and firmness. The short-term freezing after ultrarapid chilling of musculature with normal glycolysis led to cold shortening with contraction of the sarcomeres by 33.5% (m. longissimus dorsi) and 38.3% (m. semimembranosus). At the same time, a massive increase in shear force and firmness was observed. After ageing up to 48h post-mortem the sarcomeres increased in length, whereby, in comparison with the measurements before the beginning of the chilling, 88 and 84% of the original length was attained, respectively. In addition, ageing led to a significant improvement of tenderness. After ageing for more than 72h the shear force and the firmness of meat specimens chilled under normal and ultrarapid conditions became more similar. The lenghts of the sarcomeres and the shear force of musculature with accelerated glycolysis were glycolysis were not affected by the chilling procedure. PMID- 22059750 TI - Effect of pre-scalding brushing on contamination level of pork carcasses during the slaughtering process. AB - The number of aerobic bacteria on the skin of pork carcasses was measured at seven different points on the slaughtering line in order to study the hygienic effect of pre-scalding brushing on the contamination level of carcasses. Eighty carcasses were investigated, of which 40 were brushed before scalding and 40 served as controls. Samples were excised from three sites: back, abdomen and ham. The total number of samples was 1368. The cleaning monitoring of the pre-scalding brushing machine and the blackscraping machine was done at the same time. After singeing and blackscraping there were significant differences (P<0.05) between brushed and non-brushed ham sites. After singeing, brushed ham sites had a contamination level of 2.11 (log(10) cm(-2)) and non-brushed ham sites a level of 1.57. After blackscraping the contamination of brushed ham sites was 3.45 (log(10) cm(-2)) and that of non-brushed ham sites 3.26. At the end of the slaughtering line brushed carcasses were more contaminated than those not brushed, although this difference was not significant. PMID- 22059751 TI - The effect of boning and plant cleaning on the contamination of beef cuts in a commercial boning hall. AB - A series of experiments was carried out to determine the effect of boning and trimming on the bacteriology of a number of beef cuts. At the same time the plant cleaning programme was investigated to determine its efficiency in reducing bacterial numbers on different surfaces within the boning hall. The hygiene of the personnel involved in boning was also studied. The work showed that the level of contamination varied with the different cuts of meat. On the striploin and fillet the level of contamination was higher than on the inside or outside rounds. This variation resulted mainly from the amount of handling the meat received. The cleaning programme in the plant was shown to be very inefficient in reducing bacterial contamination. Personnel hygiene was also considered inadequate. It is probable that both surfaces and personnel were sources of contamination of the meat. PMID- 22059752 TI - A note on the use of subjective methods for assessing pig meat quality on the slaughterline. AB - The relationships between assessment of exudation from the intrascope hole, seen as a discolouration on the surface of the skin at 20h post mortem, subjective assessment of meat quality in the longissimus dorsi (LD), gluteus medius (GM) and rectus femoris (RF) muscles and objective measures of raw meat quality in the LD were determined on 100 pig carcasses representing a wide range of quality. The relationships between subjective exudation assessment and objective measures of quality were good with the best correlations being found with those measures indicating pale, soft, exudative (PSE), those with objective indicators of dark, firm, dry (DFD) being poorer. The relationships between subjective assessment of quality in the LD, GM and RF and all objective measures of meat quality in the LD were high. The appearance of any of the muscles could be used to predict overall meat quality in the carcasses after cutting. The subjective assessment of exudation was therefore a good, non-invasive predictor of severe PSE, but not DFD meat, which could be applied on the line after overnight chilling. After butchery, subjective assessment of LD, GM or RF muscles could be used to identify both PSE and DFD carcasses. PMID- 22059753 TI - Improvement of shelf-life and wholesomeness of ground beef by irradiation 1. Microbial aspects. AB - Various doses of ionizing radiation (cobalt-60) were used to improve the microbiological quality of commercial ground beef. The study included the isolation and identification of the natural microbial flora. The radioresistance of the individual strains was investigated. D(10) values, obtained in a saline solution, showed values ranging from 0.035 to 1.827 kGy. Treatment of ground beef with gamma radiation at doses of 1.0, 2.5 and 5.0 kGy resulted in extended shelf life at 4 degrees C of 4, 10 and 15 days, respectively while the control samples already exceeded 10(7) colony forming units (CFU)/g on day 0. Dominant groups of bacteria shifted from Gram-negative bacilli to Gram-positive cocci as the irradiation dose increased. Gram-negative cocci as well as yeasts and moulds also developed in greater proportion during storage of the irradiated samples. PMID- 22059754 TI - The influence of mincing and temperature of storage on the oxidation of pork back fat and its effect on water- and fat-binding in finely comminuted batters. AB - Besides the ability of swollen and dissolved meat proteins to form a heatstable network in finely comminuted sausage batters, the fat in the batter is an additional factor of batter stability. Fat cell integrity and the melting point of fat are regarded in the literature as essential for fat retention. In practice, however, butchers report that slaughterfresh pork back fat, whilst within a few hours post mortem and still hot, enhances batter stability compared with chilled and stored back fat. Experiments confirmed this observation. There could be several reasons for this behaviour. One would be the oxidation processes in pork fat which occur on storage. The experiments reported here show that rancidity of fat has little or no influence on batter stability. Disintegration of fat cells by mincing and/or fat softness by increased temperature, enhance batter stability. The conclusion drawn emphasizes the importance of the early formation of small fat particles in the batter for batter stability. PMID- 22059755 TI - A rapid and simple method for preparing pork with very low bacterial contamination. AB - A method for obtaining essentially bacteria-free raw meat is described. A technique of this type is necessary if intrinsic meat processes during storage are to be studied. Four cold-boned loins (M. longissimus dorsi, ML) of two pigs were fried for 2 min in frying fat at 180 degrees C and divided aseptically into eight cuts. These cuts were vacuum packaged and stored at 0 and 20 degrees C. The total aerobic count of all cuts was below 10(4) colony forming units (CFU)/cm(2) after 8 weeks of storage at 0 degrees C. At 20 degrees C, these values were much higher. Essentially the same results were found in a similar experiment in which the fried parts of the chops were removed aseptically. In a third experiment it was shown that the bacterial contamination of the cuts remained below 10(4) CFU/cm(2) during 4-6 weeks of storage at 5 degrees C. A control experiment included temperature measurement during and after frying. It was shown that after frying the ML must be cut immediately. Microscopic examination at different depths showed protein denaturation to a depth of 10 mm, indicating the necessity of removal of the outer layer. Frying appears to be a simple and rapid method of achieving virtually bacteria-free meat. Adaptation of the frying time is expected to be necessary to make the method applicable for muscles other than the ML. PMID- 22059756 TI - Pressure-induced conversion of alpha-connectin to beta-connectin. AB - The mechanism of the pressure-induced tenderization of meat has not been fully established in spite of its beneficial effect. To detect the changes in the large structural proteins of the myofibrils induced by pressurization without heat treatment, high hydrostatic pressure (100-300 MPa) was applied to rabbit at-death skeletal muscle for 10 min at low temperature (0-2 degrees C). Significant differences in the electrophoretic pattern of connectin (also called titin) in isolated myofibrils were observed between the control and pressurized muscle samples. The conversion of alpha-connectin (2800 kDa) to beta-connectin (2100 kDa) was accelerated with increasing pressure applied to the muscle; also nebulin (800 kDa) was degraded by pressure treatment. From the results it is clear that the degradation of connectin is induced by pressurization alone without heat treatment. If the conversion of alpha-connectin to beta-connectin during conditioning has some influence on meat tenderization, the pressure-induced conversion of alpha- to beta-connectin is possibly one of the causes of pressure induced tenderization of meat. PMID- 22059757 TI - Structure, bonding, and phase relations in Bi2Sn2O7 and Bi2Ti2O7 pyrochlores: new insights from high pressure and high temperature studies. AB - One of the key points of interest in pyrochlore materials containing bismuth derives from the dielectric properties of some such materials that are linked to the displacements of the bismuth atoms from the ideal site. This study uses high pressure to probe the variations in, and causes of, these displacements. Under compression Bi(2)Ti(2)O(7) does not undergo any phase changes, but Bi(2)Sn(2)O(7) undergoes a similar series of changes to those observed during heating. The trigonal beta-Bi(2)Sn(2)O(7) structure is solved from high temperature powder neutron diffraction data and hence the sequence of phases observed in Bi(2)Sn(2)O(7) is discussed for the first time. The variation in Bi displacements can be considered in terms of the frustration of the tetrahedral lattice that accommodates them. It can also be inferred that the main driver for Bi displacement is a deficiency in the bond valence sum of bismuth. PMID- 22059758 TI - Effects of gamma irradiation on the distribution of calcium ions in grass shrimp (Phenaeus monodon F.) muscle. AB - Effects of medium-dose (5 kGy) irradiation on the calcium ion distribution in shrimp muscle were studied using an electron microprobe (EDX) and an electron microscope. In irradiated shrimp muscle cells, the calcium ions in the sarcoplasmic reticulum and nuclei were not released to the myofibrils, and remained in situ during 8 days storage at 4 degrees C after irradiation. However, without irradiation the concentration of calcium ions in the myofibrils of muscle cells increased after the same storage period. The distribution of calcium ions could play a role in the softening of shrimp meat, induced by proteinase. PMID- 22059759 TI - Influence of processing temperature on the formation of biogenic amines in dry sausages. AB - Temperature is known to have a clear influence on the formation of biogenic amines in the fishing industry and in cheese fermentation In this work, the effect of processing temperature on the formation of amines in dry sausages was studied in pilot and factory trials. Sausages made from the same batch of raw materials, were divided into two groups each fermented at different processing temperatures. The influence of raw materials on amine formation was evident. When commercial preparations of starter cultures containing lactic acid bacteria and Staphylococcus carnosus were used, a lower processing temperature resulted in higher levels of amines and delayed pH decrease in comparison with the higher temperature. However, more amines were formed at the higher processing temperature when glucono-delta-lactone with S. carnosus was used. According to these results not only the selection of raw materials, but also the choice of optimal processing temperature for the amine-negative starter culture used, are important critical control points in preventing the formation of high levels of biogenic amines in dry sausages. PMID- 22059760 TI - Rheological changes during isothermal holding of salted beef homogenates. AB - The gelation of lean meat homogenates was examined in a thermal scanning rheology monitor, a device that non-destructively measures rigidity and elasticity, as response to a repetitive small movement. Salted (NaCl and pyrophosphate) homogenates were scanned from 10 degrees C to 85 degrees C at 1 degrees C/min, continuously or with an isothermal hold period at 25, 35, 45, 50 or 55 degrees C. The intention of isothermal holding was to visualize key features of the gelation process. Whatever the thermal path, the final properties of the gel were substantially the same. This indicates that heat-mediated gelation follows only one path and is complete by 85 degrees C. The hold at 55 degrees C yielded the most information on gelation. During the hold, gelation was very nearly complete while rigidity steadily increased. This showed that transition from the sol state to the gel and rigidity development are separate events. Samples held at 25 degrees C underwent pH-dependent transitions in rheological properties but at higher hold temperatures these transitions were often not observed. They were caused by a progressive loss of pyrophosphate due to an endogenous pyrophosphatase. The pH and temperature dependencies of the transitions were easily explained by classic enzymology. The enzyme activity could be inhibited by 10 mm NaF. Under these conditions the onset of final gelation occurred at a slightly, but significantly, lower temperature. Models to explain this and another subtle effect of pyrophosphate are presented. At a given pH, although gelation is subtly affected by pyrophosphate, the final rigidity and elasticity are much the same in its presence or absence. Pyrophosphate is in near universal use in salted meat products. Presumably its reported advantages, better water holding capacity and greater gel strength, are not revealed by the thermal scanning technique. PMID- 22059761 TI - Effects of Postmortem time of calcium chloride injection on beef tenderness and drip, cooking, and total loss. AB - The effect of postmortem time of calcium chloride (CaCl(2)) injection in conjunction with postmortem aging was determined on 16 beef semimembranosus muscles. Each muscle was cut into four equal segments that were randomly assigned: (1) no injection (control); (2) CaCl(2) at 1 h postmortem; (3) CaCl(2) at 12 h postmortem; or (4) CaCl(2) at 24 h postmortem. Samples were injected with a 0.3 m solution of CaCl(2) at 10% by weight. At 24 h postmortem, each segment was divided into two pieces that were randomly assigned to either a 10-day aging period (2 degrees C) or to frozen storage (-29 degrees C). Shear force values were higher (P < 0.01) in control samples compared with injected samples and increased linearly (P < 0.05) with time of injection. Drip loss was lower (P < 0.01) in control samples compared with injected samples. A linear (P < 0.05) effect was found for the increases in cooking and total loss due to injection time. Aging decreased (P < 0.05) shear force values and cooking loss. CaCl(2) injection at 1 h postmortem was most effective in reducing shear force values and preventing excessive moisture loss. However, injection at 12 or 24 h postmortem was also effective in lowering shear force values. PMID- 22059762 TI - Differences of post-mortem ATP turnover in skeletal muscle of normal and heterozygote malignant-hyperthermia pigs: Comparison of (31)P-NMR and analytical biochemical measurements. AB - Energy metabolism of the biceps femoris muscle of normal and heterozygote malignant-hyperthermia pigs was studied post-mortem after in-vivo exposure to a combination of halothane and succinylcholine. The pigs were anaesthetized with halothane and subsequently captive-bolt-stunned immediately after intravenous administration of succinylcholine. Cardiac arrest occurred within one minute after the depolarizing neuromuscular blocking with succinylcholine. During the following 2-5 hours post mortem, the level of several metabolites, reflecting the rate of muscle glycogenolysis and glycolysis, was measured by analytical biochemical techniques and by in situ (31)P-NMR spectroscopy. Both techniques demonstrated more than three-fold-accelerated PCr decay, matched by a similar increase of P(i) in heterozygotes compared with normal pigs. The rate of pH decrease and of lactate accumulation was also three to five times higher in the heterozygotes, all-in-all demonstrating a significantly increased ATP turnover post mortem in these animals when exposed to a combination of halothane and succinylcholine. The results are consistent with the notion of increased excitability of skeletal muscle due to a genetically altered calcium-channel protein. In addition, the results suggest that NMR identification of heterozygote malignant-hyperthermia pigs is possible. PMID- 22059763 TI - Physical and sensory characteristics of Najdi-camel meat. AB - Steaks were fabricated from three wholesale cuts: rib, chuck and leg of 18 Najdi male camels averaging eight, 16 and 26 months of age. The influence of age, type of cut, freezing and cooking method on the physical and palatability traits of meat has been investigated. The results indicated that age had a significant influence on cooking loss and shear value, but there was no significant effect on drip loss, expressible moisture and organoleptic properties (tenderness, juiciness and flavour). However, steaks from younger camels were more acceptable. The results also showed that wholesale cut significantly affects cooking loss, shear force value, tenderness, juiciness and flavour, but the effect on drip loss and expressible moisture was not significant. Generally, the ribeye steak had the lowest cooking loss and shear value, also the highest organoleptic scores. Except for cooking loss, freezing and cooking method had no significant effect on shear value and organoletic properties. The acceptability of camburger was also studied. Added fat resulted in higher cooking loss, but the sensory panel ratings were not significantly affected. PMID- 22059764 TI - Nutrient composition of Najdi-camel meat. AB - The proximate composition, amino-acid composition, and inorganic nutrients of different wholesale cuts and organs of 18 (six each at eight, 16, and 26 months) Najdi male camels have been determined. Skeletal muscles contained 68.8-76% moisture; 19.4-20.5% protein; 4.1-10.6% fat, and 1.0-1.1% ash. In proximate composition, camel meat is generally similar to beef. Significant differences (p < 0.05) in moisture, fat, potassium, sodium, magnesium, iron, and zinc were found between samples. The meat protein tended to have a higher percentage of the amino acid proline than literature values for other red meats, and lower values for tryptophan, aspartic acid, and tyrosine. Differences were observed between skeletal muscles and organs in nutrient content. Organs have higher percentages of ash, sodium, and iron than skeletal muscles. Among organs, kidneys contained higher quantities of moisture, calcium, and sodium but lower values of protein, magnesium, and potassium than liver and heart meats. PMID- 22059765 TI - Comparison of some components of pigs kept in natural (free-range) and large scale conditions. AB - A new pig genotype of Hungarian Large White (75%) * Mangalica (pig with curly bristles, 25%) was used in the experiments. The experimental group was kept in a farming system under strictly natural circumstances until a body weight of 120 kg was attained. Neither antibiotics nor yield-increasing hormones were given to this group. The control group was kept in the usual large-scale farming conditions until body weight of 120 kg was attained. In most cases, protein, zinc, and copper levels and, in some cases, iron levels were significantly higher in some major cuts (neck-end (Boston-butt), loin, ham) of the 'free-range' pigs (n = 12) in comparison with the control animals kept in large-scale farming conditions. There was, on average, 15% less cholesterol in the muscles and 30% less cholesterol in the liver and less linoleic acid in all tissues of 'free range' pigs than in the control group. There was less fat, but the amount of thiamin and riboflavin in the liver of the naturally kept pigs was twice that in the controls. In respect of TBA-reactive compounds, there were no significant differences between the two groups, but superoxide dismutase (SOD) showed significantly higher activities in all cuts from pigs kept in a large-scale farming system. This may be the effect of a higher level of linoleic acid in the fat. PMID- 22059766 TI - Relationship between USDA and Japanese beef grades. AB - Angus steers (n = 78) were feedlot-finished to approximately 703 kg live weight. The finished steers were slaughtered at a commercial packing plant, chilled, and evaluated for USDA and Japanese yield and quality-grade characteristics. The resulting carcasses were excessively heavy and fat for the domestic (US) beef industry. Over 70% of the carcasses were US Yield Grade 5, and almost 40% were Japanese Yield Score 'C'. Although excessively fat externally, fewer than 50% of the carcasses qualified for US Prime, and none of the carcasses qualified for Japanese Meat Quality Score 5. Moderate to high correlations were observed between US twelfth-rib carcass traits and Japanese sixth-rib traits; however, multiple-regression equations based on USDA carcass characteristics explained only 46 and 25% of the observed variation in Japanese marbling score and estimated percentage wholesale-cut yield, respectively. PMID- 22059767 TI - Rheological parameters as predictors of protein functionality: A model study using myofibrils of different fibre-type composition. AB - The rheology of myofibrils from a typical red muscle, m. masseter, and a typical white muscle, m. cutaneus trunci, has been studied at different pH values and salt and myofibrillar-protein concentrations. The storage modulus G' and the phase angle delta were related to the parameters pH, salt, and muscle, by using partial-least-square-two-block modelling. At high and low temperatures, G' was largely affected by pH and salt, respectively. For delta, the reverse was observed. The peak G' observed at temperatures between 40 and 60 degrees C is an indicator of salt addition above the physiological salt level for both types of myofibrillar system. The magnitude of the change in G' per degree, in the temperature range 40-60 degrees C, was the most muscle-specific parameter observed, and the peak was larger for cutaneus trunci than masseter myofibrils. At high temperatures (80 degrees C), the cutaneus trunci myofibrils, for technical relevant conditions, formed stronger gels than masseter myofibrils. The cutaneus trunci systems also aggregated more strongly and exuded more water than systems of masseter myofibrils. The effect of strain on G' was generally larger for cutaneus trunci than for masseter myofibrillar systems. Many observations on myofibrillar systems were transferable to real-meat systems, which were also examined. PMID- 22059768 TI - Sugar-beet pulp as an alternative ingredient of barley in rabbit diets and its effect on rabbit meat. AB - The effects of rabbit diets with four different levels of barley and sugar-beet pulp on the dressing percentage, chemical and fatty acid composition of meat from rabbits slaughtered at a liveweight of 2000 and 2500 g have been studied. Results revealed detectable (P < 0.05) effects of the total substitution of barley by sugar-beet pulp for carcass weight, dressing percentage and dry matter from animals slaughtered at a liveweight of 2000 g. No significant differences (P > 0.05) among batches were observed when slaughter weight was 2500 g. No influence of the diet on the total lipid fatty acids was found. In general, similar results were found when rabbit diets were formulated with 50% barley and 0% sugar-beet pulp, 30% barley and 0% sugar-beet pulp or 15% barley and 15% sugar-beet pulp. PMID- 22059769 TI - Sex-specific identification of raw meat from cattle, buffalo, sheep and goat. AB - A simple and reliable method has been developed for accurate identification of male and female raw meats in cattle, buffalo, sheep and goat using the polymerase chain reaction (PCR) technique. The PCR assay was conducted on genomic DNA extracted from raw muscle tissue of male and female animals. The method has been found to be accurate, reliable and quick. PMID- 22059770 TI - Structural weakening of intramuscular connective tissue during conditioning of beef. AB - The structural changes in intramuscular connective tissues endomysium and perimysium during conditioning of beef were investigated using an improved technique of scanning electron microscopy. In beef conditioned for 28 days of 4 degrees C, the endomysium resolved into individual collagen fibrils and the thick sheets of perimysium separated into collagen fibres of 4-8 MUm in diameter. These results provide direct evidence for the structural weakening of endomysium and perimysium during conditioning. The structural changes in the intramuscular connective tissue were minimal until 10 days post mortem, but clearly observable after 14 days post mortem. Therefore, it is concluded that intramuscular connective tissue shows the effect on tenderisation of extended conditioning (2-4 weeks) of beef. PMID- 22059771 TI - Structural weakening of intramuscular connective tissue during post mortem ageing of chicken Semitendinosus muscle. AB - The structural changes in intramuscular connective tissues endomysium and perimysium during post mortem ageing in chicken semitendinosus muscle were investigated using an improved technique of scanning electron microscopy. In post mortem chicken aged for 12 h at 4 degrees C, the endomysium resolved into individual collagen fibrils and the perimysial sheets separated into collagen fibres. These results provide direct evidence for the structural weakening of endomysium and perimysium during post mortem ageing. The structural changes in the intramuscular connective tissue were minimal until 6 h post mortem, but clearly observable after 12 h post mortem. It was concluded that this disintegration of the intramuscular connective tissue is the chief mechanism in tenderisation during extended post mortem ageing of chicken. PMID- 22059772 TI - Sensory evaluation of beef-flavor-intensity, tenderness, and juiciness among major muscles. AB - Twelve muscles from eight USDA Select/Choice grade steers were evaluated for beef flavor intensity, tenderness, and juiciness. The biceps femoris, psoas major, gluteus medius, semimembranosus, and triceps brachii were similar in beef-flavor intensity (P > 0.05) and were ranked as the most intensely flavored of all muscles. The rectus femoris, longissimus lumborum, serratus ventralis, infraspinatus, semitendinosus, pectoralis profundus, and supraspinatus generally were less intense in beef-flavor than the other muscles and were ranked from highest to lowest intensity in that order. The psoas major was the most tender (P > 0.05) followed by the infraspinatus, longissimus lumborum, and rectus femoris, which were similar (P > 0.05). Generally, muscles from the chuck and loin were juicier than those from the round. PMID- 22059773 TI - Microbial growth and biochemical changes on naturally contaminated chilled-beef subcutaneous adipose tissue stored aerobically. AB - Naturally contaminated beef-brisket fat showed a psychrotroph count of 4 * 10(9) CFU/cm(2) after 14 days of aerobic refrigerated storage (5 degrees C +/- 1 degrees C). Pseudomonas was the predominating genus. Other micro-organisms, such as Enterobacteriaceae and Brochothrix thermosphacta, grew up to 2.5 * 10(8) cfu/cm(2) and 1.6 * 10(8) cfu/cm(2), respectively. Concentrations of different substrates that could support microbial growth were measured. Glucose concentration dropped to approximately one-third of the initial level during the first week of storage. Lactic acid also declined. Free fatty acids increased significantly (P < 0.05) during refrigeration. However, other lipid-deterioration indices, such as the thiobarbituric acid number and the peroxide value, remained unchanged. Beef subcutaneous fat had a high initial microbial load and a capacity to support extensive bacterial growth. It may therefore constitute an important source of contamination for meat and manufactured meat products. PMID- 22059774 TI - Obituary: ronald harry locker (1927-1994). PMID- 22059775 TI - Sulfoquinovose synthase - an important enzyme in the N-glycosylation pathway of Sulfolobus acidocaldarius. AB - Recently, the Surface (S)-layer glycoprotein of the thermoacidophilic crenarchaeote Sulfolobus acidocaldarius was found to be N-glycosylated with a heterogeneous family of glycans, with the largest having a composition Glc(1)Man(2)GlcNAc(2) plus 6-sulfoquinovose. However, genetic analyses of genes involved in the N-glycosylation process in Crenarchaeota were missing so far. In this study we identify a gene cluster involved in the biosynthesis of sulfoquinovose and important for the assembly of the S-layer N-glycans. A successful markerless in-frame deletion of agl3 resulted in a decreased molecular mass of the S-layer glycoprotein SlaA and the flagellin FlaB, indicating a change in the N-glycan composition. Analyses with nanoLC ES-MS/MS confirmed the presence of only a reduced trisaccharide structure composed of Man(1) GlcNAc(2) , missing the sulfoquinovose, a mannose and glucose. Biochemical studies of the recombinant Agl3 confirmed the proposed function as a UDP-sulfoquinovose synthase. Furthermore, S. acidocaldarius cells lacking agl3 had a significantly lower growth rate at elevated salt concentrations compared with the background strain, underlining the importance of the N-glycosylation to maintain an intact and stable cell envelope, to enable the survival of S. acidocaldarius in its extreme environment. PMID- 22059776 TI - Remission of acquired von Willebrand syndrome after successful treatment of gastric MALT lymphoma. PMID- 22059777 TI - The Wartegg Zeichen Test: a literature overview and a meta-analysis of reliability and validity. AB - All available studies on the Wartegg Zeichen Test (WZT; Wartegg, 1939) were collected and evaluated through a literature overview and a meta-analysis. The literature overview shows that the history of the WZT reflects the geographical and language-based processes of marginalization where relatively isolated traditions have lived and vanished in different parts of the world. The meta analytic review indicates a high average interscorer reliability of rw = .74 and high validity effect size for studies with clear hypotheses of rw = .33. Although the results were strong, we conclude that the WZT research has not been able to establish cumulative knowledge of the method because of the isolation of research traditions. PMID- 22059778 TI - Atrial dysfunction and interatrial dyssynchrony predict atrial high rate episodes: insight into the distinct effects of right atrial appendage pacing. AB - INTRODUCTION: Right atrial (RA) appendage pacing may prolong atrial conduction time (ACT). This study aimed to investigate if RA appendage pacing can induce intra- and interatrial dyssynchrony and if atrial dysfunction and dyssynchrony can predict atrial high rate episodes (AHREs) in the first year after pacing. METHODS AND RESULTS: Patients implanted with dual-chamber pacemakers for symptomatic bradycardia were enrolled. Cumulative percentage of RA appendage pacing (Cum%AP) during 1-year follow-up and AHREs were recorded. Full Doppler echocardiography studies were performed before implantation and 1 year after pacing. ACT and peak atrial velocities (Sm-la, Em-la, Am-la) were measured. One hundred ten patients (age 70.5 +/- 11 years; 53 males) were recruited and completed 1-year follow-up. ACT of both RA and left atrial (LA) were more prolonged in patients with Cum%AP > 75% than those with <25%. Intra- and interatrial dyssynchrony was more obvious in patients with Cum%AP > 75% (22.3 +/- 12.2 milliseconds vs 9.5 +/- 6.2 milliseconds; 53.9 +/- 29.7 milliseconds vs 19.7 +/- 17.3 milliseconds; both P < 0.001). AHREs occurred in 29% of patients. Atrial pump function and interatrial dyssynchrony independently predicted AHREs in multivariate analysis. Receiver operating characteristic curve provided a cutoff value of Am-la <5.3 cm/s, which predicted AHREs with a sensitivity of 71% and a specificity of 75% (area under the curve, 0.822; P < 0.001). CONCLUSION: RA appendage pacing causes atrial conduction delay with intra- and interatrial dyssynchrony. Atrial dysfunction and interatrial dyssynchrony are related to AHREs in the first year after pacing. PMID- 22059779 TI - Improving the electrical conductivity of carbon nanotube networks: a first principles study. AB - We address the issue of the low electrical conductivity observed in carbon nanotube networks using first-principles calculations of the structure, stability, and ballistic transport of different nanotube junctions. We first study covalent linkers, using the nitrene-pyrazine case as a model for conductance-preserving [2 + 1] cycloadditions, and discuss the reasons for their poor performance. We then characterize the role of transition-metal adsorbates in improving mechanical coupling and electrical tunneling between the tubes. We show that the strong hybridization between the transition-metal d orbitals with the pi orbitals of the nanotube can provide an excellent electrical bridge for nanotube nanotube junctions. This effect is maximized in the case of nitrogen-doped nanotubes, thanks to the strong mechanical coupling between the tubes mediated by a single transition metal adatom. Our results suggest effective strategies to optimize the performance of carbon nanotube networks. PMID- 22059780 TI - Using theory to identify beliefs associated with support for policies to raise the price of high-fat and high-sugar foods. AB - Public policies designed to dramatically raise the price of high-fat and high sugar foods have received substantial attention from researchers and the media. Although econometric studies suggest that these policies could reduce obesity rates, they are likely to face substantial public opposition. This study used the theory of perceived responsibility and social motivation as a framework to analyze data from a politically diverse convenience sample of 500 adults in upstate New York. The authors examined associations between attribution beliefs and policy support to identify what types of scientific evidence and accompanying messages appear most likely to generate public support for price-raising policies. Results suggest that public health advocates and health communicators could benefit from an increased emphasis on advertising for unhealthy foods as a cause of obesity and the food industry's (manufacturers, advertisers, markets, and restaurants) responsibility for addressing the problem. PMID- 22059781 TI - Implementing a pathway for the management of acute coronary syndrome leads to improved compliance with guidelines and a decrease in angina symptoms. AB - We describe our experience with the Advanced Cardiac Admission Program (ACAP) at our institution. The ACAP program is a hospital-wide implementation of critical pathways-based management of all cardiac patients. Data review of patients admitted for acute coronary syndromes from the ACAP-PAIN database and a comparative study of outcomes before and after implementation of the pathways based assessment and treatment protocols. In the pre-ACAP and post-ACAP patient groups, antiplatelet use at admission improved from 50% to 75% (p<.01), ACE-I use improved from 32% to 54% (p<.0001), statins use increased from 35% to 62% (p<.0001), and smoking cessation awareness increased from 15% to 86% (p<.0001). At 1-year follow-up, 84% of patients with CAD were treated with statins, and 47% had LDL cholesterol <100 mg/dL, compared with 20% and 9%, respectively, with conventional treatment before ACAP implementation (p<.0001). Recurrent angina symptoms and nonfatal myocardial infarction rates decreased from 28.5% to 13% (p = .02), and 15% to 5% (p = 0.03), respectively. Pathway-based programs like ACAP significantly enhance administration of guidelines-based cardioprotective medications both during hospital stay and at 1-year follow-up. PMID- 22059783 TI - Less RAAS is more, or not. PMID- 22059784 TI - Will apoA-I-based therapies step up to cure coronary artery disease? PMID- 22059786 TI - Diltiazem in the treatment of hypertension and ischemic heart disease. AB - Treatment of patients with hypertension and ischemic heart disease should be focused not only on the control of overall cardiovascular risk factors, particularly blood pressure, but also on eliminating anginal symptoms, or at least reducing them, as angina symptoms have a crucial prognostic value. Although the amount of blood pressure reduction, rather than the choice of antihypertensive drug, is the major determinant of reduction of cardiovascular risk, some drugs such as ?-blockers should be preferably used in patients with angina. However, ?-blockers are contraindicated or produce intolerable side effects in many patients. Although, in the last years, new drugs for the treatment of stable angina have emerged, diltiazem should remain as a good alternative in the treatment of these patients. In this article, available evidence regarding diltiazem in the treatment of hypertension and ischemic heart disease is updated. PMID- 22059787 TI - Clinical experience with rosuvastatin in the management of hyperlipidemia and the reduction of cardiovascular risk. AB - On the basis of large randomized clinical trials, pharmacological antagonists of HMG-CoA reductase (statins) have become increasingly used in clinical practice for the prevention of cardiovascular disease. Rosuvastatin was developed as a potent statin, which appeared to raise levels of HDL-cholesterol, in addition to marked reductions in levels of LDL-cholesterol. These effects on lipids are associated with a beneficial impact of rosuvastatin on progression of various stages of atherosclerosis and cardiovascular outcomes in clinical trials. The clinical experience of rosuvastatin will be reviewed in this article. PMID- 22059788 TI - Atrial fibrillation catheter ablation in females: same hardware, different findings. AB - Atrial fibrillation catheter ablation has gained a significant role in the management of the frequent arrhythmia and has been shown to be safe and effective. As with many other interventional therapies, gender bias is present and females are referred for catheter ablation less frequently than their male counterparts. Women referred for catheter ablation tend to be older, more symptomatic, have failed more antiarrhythmic agents and may have poorer procedure success and increased vascular complication rates. Efforts to close this referral gap are clearly needed and it is likely that early referral will reduce gender differences in atrial fibrillation catheter ablation success rates. PMID- 22059789 TI - Should the blood pressure or the blood vessel be the target of therapy? AB - Measured blood pressure is an insensitive and moderately nonspecific guide to the presence of vascular or cardiac diseases likely to progress to cardiovascular morbid events. Since the goal of the diagnosis and treatment of hypertension is to prevent or forestall such morbid events, blood pressure measurements should be supplemented by studies of the health of the cardiovascular system in defining the syndrome of hypertension and in monitoring its response to therapy. PMID- 22059790 TI - Antiplatelet options for secondary prevention in acute coronary syndromes. AB - Current guidelines recommend dual antiplatelet therapy, a combination of aspirin and a P2Y(12) inhibitor, for 6?12 months after percutaneous coronary intervention with drug-eluting stent implantation in all patients and for 1 year in all patients after an acute coronary syndrome (ACS), irrespective of revascularization strategy. Clopidogrel has a pharmacokinetic and pharmacodynamic profile that results in a delayed and/or subtherapeutic antiplatelet effect, and wide variability in antiplatelet response. New P2Y(12) inhibitors, such as prasugrel and ticagrelor, have favorable pharmacodynamics and clinical efficacy over clopidogrel and offer an alternative antiplatelet treatment strategy in specific patients. Prasugrel has more potent, rapid, and consistent effects on inhibiting ADP-induced platelet aggregation than clopidogrel. Ticagrelor also appears to have more rapid and consistent antiplatelet effects than clopidogrel. The higher levels of antiplatelet inhibition provided by prasugrel and ticagrelor compared with standard-dose clopidogrel result in improved ischemic outcomes in patients with ACS. Despite an increase in bleeding risk, prasugrel and ticagrelor appear to have a better net clinical benefit, especially in higher-risk patients with ACS. PMID- 22059791 TI - Heart rate recovery: a practical clinical indicator of abnormal cardiac autonomic function. AB - The autonomic nervous system (ANS) and cardiovascular function are intricately and closely related. One of the most frequently used diagnostic and prognostic tools for evaluating cardiovascular function is the exercise stress test. Exercise is associated with increased sympathetic and decreased parasympathetic activity and the period of recovery after maximum exercise is characterized by a combination of sympathetic withdrawal and parasympathetic reactivation, which are the two main arms of the ANS. Heart rate recovery after graded exercise is one of the commonly used techniques that reflects autonomic activity and predicts cardiovascular events and mortality, not only in cardiovascular system disorders, but also in various systemic disorders. In this article, the definition, applications and protocols of heart rate recovery and its value in various diseases, in addition to exercise physiology, the ANS and their relationship, will be discussed. PMID- 22059792 TI - Advances in 3D echocardiography for mitral valve. AB - The advent of real-time (RT) 3D transesophageal echocardiography (TEE) in 2007 has enhanced our understanding of the location and extent of the pathology of the native, as well as prosthetic, mitral valve (MV), particularly for MV prolapse and the anatomy of perivalvular dehiscence with prosthetic MV. MV quantification programs provide precise assessment of many quantitative MV parameters allowing 3D echocardiography to determine and quantify the geometry of mitral apparatus, including mitral annulus and periannular region, leaflet volume and anatomy, tethering distances, and tenting volumes. The detailed, accurate and optimal RT spatial visualization of the MV with 3D TEE gives greater confidence to the echocardiographer, interventionalist and the surgeon alike, facilitating medical and surgical treatment decisions. This article highlights recent advances in RT 3D TEE and transthoracic echocardiography echocardiographic imaging of the MV. PMID- 22059793 TI - Pulmonary valve interventions. AB - The last decade has generated enormous advances in the diagnostic and therapeutic possibilities for diseases of the pulmonary valve. There have been advances in all age groups from fetus to adult, with not only the development of novel treatments (fetal interventions, new surgical strategies and percutaneous pulmonary valve implantation), but also an improved understanding of the long term sequelae of pulmonary valve disease. In this article, we discuss treatments of the native valve in the fetus and neonate and the management of the consequences of early interventions in later life, with the particular focus on the introduction of percutaneous pulmonary valve implantation, its follow-up and the development of new devices to treat pulmonary stenosis and incompetence without the need for open-heart surgery. PMID- 22059794 TI - Transcatheter rehabilitation of pulmonary arteries. AB - Pulmonary arterial stenoses commonly occur in patients with congenital heart disease. Indications for treatment are based around reduction of right ventricular hypertension and equalization of flow to each lung and its constituent segments. There are many treatment approaches for these lesions depending on the anatomy, location and the age of the patient. Although surgical reconstruction remains an option, it is technically challenging and in many cases, the results are disappointing. In the modern era, the majority of these patients are treated with transcatheter therapy, including balloon angioplasty, and increasingly, the use of intravascular stents. In this article, we discuss these issues and deal with both the technical approach to transcatheter therapy and up-to-date results. PMID- 22059796 TI - Current perspectives in endoscopic vessel harvesting for coronary artery bypass grafting. AB - Coronary artery bypass grafting is still the most commonly performed procedure in cardiac surgery. Minimally invasive or endoscopic vessel harvesting was developed a decade ago. It has been shown that these less traumatic techniques significantly reduce wound healing problems and improve patient satisfaction. However, there are some concerns regarding bypass patency and long-term outcomes. The aim of this article is to describe the historic development of endoscopic vessel harvesting, different harvesting techniques and to give an update of the scientific evidence and the current debate regarding outcome and safety of these minimally invasive techniques. PMID- 22059795 TI - Myocardial therapeutic angiogenesis: a review of the state of development and future obstacles. AB - A significant percentage of patients have coronary artery disease that is too advanced or diffuse for percutaneous or surgical intervention. Therapeutic angiogenesis is a treatment modality to induce vessel formation that is being developed for patients with advanced coronary disease not amenable to currently available interventions. A number of approaches to induce coronary collateralization are being developed. These include gene, protein, cellular and miRNA modalities, each of which have advantages and disadvantages. At this time, no modality has emerged as the single clear choice, and combination therapies may provide synergistic benefits. However, there have been a number of recent studies advancing our knowledge as to how we can refine procollateralizing treatments. In this article, we will examine some recent successes and future obstacles in the effort to bring therapeutic angiogenesis to patients. PMID- 22059798 TI - Osteoarthritis of the talonavicular joint with pseudarthrosis of the navicular bone: a case report. AB - INTRODUCTION: Osteoarthritis of the talonavicular joint caused by inflammatory, degenerative, and post-traumatic arthritis has been commonly described, and isolated arthrodesis for talonavicular joint has usually been performed for such conditions. However, arthritis accompanied by pseudarthrosis of the navicular bone is an extremely rare case, and to the best of our knowledge, isolated arthrodesis for this situation has not been previously described in any published reports. CASE PRESENTATION: The patient was a 39-year-old Japanese man. He had complained of pain in his left middle foot since a fall from his motorcycle six months previously. Radiographs and computed tomography (CT) scans revealed pseudarthrosis of the navicular bone. MRI indicated mild arthritic change in the talonavicular joint and avascular necrosis of the navicular bone. We performed an isolated arthrodesis of the talonavicular joint with two 6.5 mm cancellous screws. One year after the operation, radiographical bone union had been obtained, and the patient reported no pain and complete satisfaction with the result. CONCLUSIONS: Isolated talonavicular arthrodesis is one of the effective procedures for the treatment of traumatic talonavicular arthritis with pseudarthrosis of the navicular bone both in providing pain relief and functional improvement. PMID- 22059799 TI - A novel stress monitoring method through stress-induced respiratory alterations: non-contact measurement of respiratory V(T)/T(I) alterations induced by stressful sound using a 10 GHz microwave radar. AB - We have developed a non-contact stress monitoring system which measures respiratory V(T)/T(I) (tidal volume/inspiration time) alterations using a 10 GHz microwave radar. The measurable distance of the system is 50 cm, which is 10 times longer than our previously developed stress monitoring system which measures heart rate variability using a 24-GHz microwave-radar. The study was conducted with eight subjects (23 +/- 1 years old) to evaluate the efficacy of the system. An audio stimulus at 95 dB sound pressure level was presented to the subjects following a silent period of 120 seconds. During the silent period, V(T)/T(I) averaged 826 +/- 384 ml s(-1), while it increased significantly (p < 0.05) with an average of 1227 +/- 704?ml s(-1) during audio stimulus low frequency component (LF)/high frequency component (HF), which reflects sympatho vagal valance, showed a peak during audio stimuli. This paper aims to study the efficacy of the non-contact stress monitoring system for its future applications in many fields including health and safety. PMID- 22059800 TI - Assessing the cumulative effects of exposure to selected benzodiazepines on the risk of fall-related injuries in the elderly. AB - BACKGROUND: The use of benzodiazepines is associated with increased risk of fall related injuries in the elderly. However, it is unclear if the risks vary across the products and how they depend on the pattern of use and dosage. Specifically, the possibility of cumulative effects of past benzodiazepine use has not been thoroughly investigated. METHODS: We used the administrative database for a cohort of 23,765 new users of benzodiazepines, aged 65 years and older, in Quebec, Canada, between 1990 and 1994. The associations between the use of seven benzodiazepines and the risk of fall-related injuries were assessed using several statistical models, including a novel weighted cumulative exposure model. That model assigns to each dose taken in the past a weight that represents the importance of that dose in explaining the current risk of fall. RESULTS: For flurazepam, the best-fitting model indicated a cumulative effect of doses taken in the last two weeks. Uninterrupted use of flurazepam in the past months was associated with a highly significant increase in the risk of fall-related injuries (HR = 2.83, 95% CI: 1.45-4.34). The cumulative effect of a 30-day exposure to alprazolam was 1.27 (1.13-1.42). For temazepam, the results suggested a potential withdrawal effect. CONCLUSIONS: Mechanisms affecting the risk of falls differ across benzodiazepines, and may include cumulative effects of use in the previous few weeks. Thus, benzodiazepine-specific analyses that account for individual patterns of use should be preferred over simpler analyses that group different benzodiazepines together and limit exposure to current use or current dose. PMID- 22059802 TI - Seeing minds: A neurophilosophical investigation of the role of perception-action coupling in social perception. AB - This paper proposes an empirical hypothesis that in some cases of social interaction we have an immediate perceptual access to others' minds in the perception of their embodied intentionality. Our point of departure is the phenomenological insight that there is an experiential difference in the perception of embodied intentionality and the perception of non-intentionality. The other's embodied intentionality is perceptually given in a way that is different from the givenness of non-intentionality. We claim that the phenomenological difference in the perception of embodied intentionality and non intentionality translates into an account of how, in some cases of social cognition, we perceive mental properties in the perception of embodied intentionality. The hypothesis derives support from a host of recent empirical studies in social neuroscience which demonstrate the importance of embodied engagements in understanding other minds. These studies reveal that embodied intersubjective interaction often builds on our ability to understand other minds in an immediate perceptual way not adequately investigated by theory-theory (TT) and simulation theories (ST) of mind-reading. We argue that there is a genuine, nontrivial difference in the informational content of the perception of embodied intentionality and the perception of non-intentionality which leads to a further difference in the way information is processed in the case of perception of embodied intentionality as opposed to the perception of non-intentionality. The full significance of such difference is appreciated only within an account of perception which views perception and action as tightly coupled. Thus, we propose an "action-oriented account of social perception" to develop a neurophilosophical account of the perceptual knowledge of other minds. PMID- 22059801 TI - Measurement properties of physical function scales validated for use in patients with rheumatoid arthritis: a systematic review of the literature. AB - BACKGROUND: The aim of this study was to systematically review the content validity and measurement properties of all physical function (PF) scales which are currently validated for use with patients with rheumatoid arthritis (RA). METHODS: Systematic literature searches were performed in the Scopus and PubMed databases to identify articles on the development or psychometric evaluation of PF scales for patients with RA. The content validity of included scales was evaluated by linking their items to the International Classification of Functioning Disability and Health (ICF). Furthermore, available evidence of the reliability, validity, responsiveness, and interpretability of the included scales was rated according to published quality criteria. RESULTS: The search identified 26 questionnaires with PF scales. Ten questionnaires were rated to have adequate content validity. Construct validity, internal consistency, test retest reliability and responsiveness was rated favourably for respectively 15, 11, 5, and 6 of the investigated scales. Information about the absolute measurement error and minimal important change scores were rarely reported. CONCLUSION: Based on this literature review, the disease-specificHAQ and the generic SF-36 can currently be most confidently recommended to measure PF in RA for most research purposes. The HAQ, however, was frequently associated with considerable ceiling effects while the SF-36 has limited content coverage. Alternative scales that might be better suited for specific research purposes are identified along with future directions for research. PMID- 22059803 TI - Low HDL predicts differential blood pressure effects from two weight-loss approaches: a secondary analysis of blood pressure from a randomized, clinical weight-loss trial. AB - Examining predictors of blood-pressure (BP) response to weight-loss diets might provide insight into mechanisms and help guide clinical care. We examined whether certain baseline patient characteristics (e.g. diet, medical history and laboratory tests) predicted BP response to two weight-loss diet approaches that differ in macronutrient content. One hundred and forty-six overweight adult outpatients were randomized to either a low-carbohydrate diet (N = 72) or orlistat plus a low-fat diet (N = 74) for 48 weeks. Predictors of BP reduction were evaluated using a structured approach and random effects regression models. Participants were 56% African-American, 72% male and 53 (+/-10) years-old. Of the variables considered, low baseline high-density lipoprotein (HDL) predicted greater reduction in BP in those patients who received the low-carbohydrate diet (p = 0.03 for systolic BP; p = 0.03 for diastolic BP and p = 0.02 for mean arterial pressure). A low HDL level may identify patients who will have greater BP improvement on a low-carbohydrate diet. PMID- 22059804 TI - Impact of moderate vs stringent TSH suppression on survival in advanced differentiated thyroid carcinoma. AB - OBJECTIVES: To assess (i) the influence of Thyrotropin (TSH) suppression at a level of <0.1 mU/l and (ii) whether FT3 and FT4 levels have a prognostic significance independently of TSH values with regard to survival in patients with differentiated thyroid carcinoma (DTC) and distant metastases. PATIENTS AND METHODS: In a retrospective patient chart study, we reviewed survival in 157 DTC patients with distant metastases treated between September 1985 and 1 July 2010. Patients with at least three available FT3 and FT4 values during TSH suppression were eligible. RESULTS: Fifty-three of 157 patients died from DTC. DTC-specific survival was significantly better in patients with a median TSH level <=0.1 mU/l (median survival 15.8 years) than those with a non-suppressed TSH level (median survival 7.1 years; P < 0.001). However, there was no further improvement in survival caused by TSH suppression to a level <= 0.03 mU/l (P = 0.24). FT3 and FT4 levels were also significantly associated with poorer survival; of these, only the prognostic value of FT3 was independent from that of TSH levels. CONCLUSION: The care of patients with DTC and distant metastases is like walking an endocrinological tightrope: non-suppressed TSH levels, that is, >0.1 mU/l, are associated with an impaired prognosis. There is, however, no prognostic benefit from suppressing TSH to levels lower than 0.1 mU/l. On the contrary, an improvement in prognosis might be achieved by keeping FT3 levels as low as possible. PMID- 22059805 TI - Metastable patterning of plasma nanocomposite films by incorporating cellulose nanowhiskers. AB - A new method is presented for developing patterned, thin nanocomposite films by introducing cellulose nanowhiskers during the pulsed plasma polymerization of maleic anhydride. Metastable film structures develop as a combination of dewetting and buckling phenomena. By controlling the maleic anhydride monomer to cellulose nanowhisker weight ratio, the whiskers can be incorporated into a homogeneously covering patterned polymer film. Excess nanowhiskers are required to prevent complete dewetting and deposit dimensionally stable films. The formation of anchoring points is assumed to stabilize the film through a "pinning" effect to the substrate. The latter control the in-plane film stresses, similar to the effects of surface inhomogeneities such as artificial scratches. The different morphologies are evaluated by optical microscopy, AFM, contact angle measurements, and ellipsometry. Further analysis by infrared spectroscopy and XPS suggests esterification between the maleic anhydride and cellulose moieties. PMID- 22059806 TI - Synthesis of alpha-glycosyl thiols by stereospecific ring-opening of 1,6 anhydrosugars. AB - Treatment of 1,6-anhydrosugars with commercially available bis(trimethylsilyl) sulfide in the presence of trimethylsilyl triflate led to the formation of alpha glycosyl thiols. All the reactions were highly stereoselective and afforded the alpha-glycosyl thiols in good to excellent yields. By this procedure, a variety of 1,6-anhydrosugars, differing in their sugar units, glycosidic linkages, and protecting group pattern, were converted smoothly into the corresponding alpha glycosyl thiols, which could be of great utility in thioglycoside chemistry. It is noteworthy that 1,6-anhydrosugars carrying the 2-O-acyl group and 1,6 anhydrosugar-containing oligosaccharides could also be ring-opened stereospecifically under the same conditions to give rise to the corresponding 1 thiosugars in high yields. Thus, a very concise and efficient access to alpha glycosyl thiols of great value was established. PMID- 22059807 TI - Acute intratracheal Pseudomonas aeruginosa infection in cystic fibrosis mice is age-independent. AB - BACKGROUND: Since the discovery of the human CFTR gene in 1989 various mouse models for cystic fibrosis (CF) have been generated and used as a very suitable and popular tool to approach research on this life-threatening disease. Age related changes regarding the course of disease and susceptibility towards pulmonary infections have been discussed in numerous studies. METHODS: Here, we investigated CftrTgH(neoim)Hgu and Cftrtm1Unc-Tg(FABPCFTR)1Jaw/J CF mice and their non-CF littermates during an acute lung infection with Pseudomonas aeruginosa for age dependent effects of their lung function and immune response.Mice younger than three or older than six months were intratracheally infected with P. aeruginosa TBCF10839. The infection was monitored by lung function of the animals using non-invasive head-out spirometry and the time course of physiological parameters over 192 hours. Quantitative bacteriology and lung histopathology of a subgroup of animals were used as endpoint parameters. RESULTS: Age-dependent changes in lung function and characteristic features for CF like a shallower, faster breathing pattern were observed in both CF mouse models in uninfected state. In contrast infected CF mice did not significantly differ from their non-CF littermates in susceptibility and severity of lung infection in both mouse models and age groups. The transgenic Cftrtm1Unc Tg(FABPCFTR)1Jaw/J and their non-CF littermates showed a milder course of infection than the CftrTgH(neoim)Hgu CF and their congenic C57Bl/6J non-CF mice suggesting that the genetic background was more important for outcome than Cftr dysfunction. CONCLUSIONS: Previous investigations of the same mouse lines have shown a higher airway susceptibility of older CF mice to intranasally applied P. aeruginosa. The different outcome of intranasal and intratracheal instillation of bacteria implies that infected CF epithelium is impaired during the initial colonization of upper airways, but not in the subsequent response of host defense. PMID- 22059808 TI - Erythrocyte sedimentation rate as an independent prognostic factor in mycosis fungoides. AB - BACKGROUND: Mycosis fungoides has a characteristically indolent clinical course, with a slow progression from patches over plaques to tumours. In advanced stages, with generalized skin involvement or tumours, the prognosis is poor. Well defined prognostic parameters for the individual risc stratifications are rare. OBJECTIVES: To determine prognostic factors for mycosis fungoides. METHODS: In a retrospective monocenter study, we reevaluated 97 consecutive cases of mycosis fungoides seen at our clinic. We correlated various routinely accessed parameters with survival data. The parameters were "sex", "age at time of diagnosis", "age adjusted erythrocyte sedimentation rate"?(ESR), and "anemia". RESULTS: We identified ESR as a highly significant prognostic marker for MF that also affects overall survival and disease specific survival (P = 0.0014). The five-years disease specific survival was 100% for patients without elevation of ESR, and 52.83% for patients with elevated ESR above normal range (P < 0.001). It is of main interest that the ESR is a significant prognostic marker also in the T2 stage of MF. For the other parameters there was no significant impact on disease specific survival. CONCLUSIONS: ESR has turned out as independent prognostic factor in mycosis fungoides. PMID- 22059809 TI - Graphene gate electrode for MOS structure-based electronic devices. AB - We demonstrate that the use of a monolayer graphene as a gate electrode on top of a high-kappa gate dielectric eliminates mechanical-stress-induced-gate dielectric degradation, resulting in a quantum leap of gate dielectric reliability. The high work function of hole-doped graphene also helps reduce the quantum mechanical tunneling current from the gate electrode. This concept is applied to nonvolatile Flash memory devices, whose performance is critically affected by the quality of the gate dielectric. Charge-trap flash (CTF) memory with a graphene gate electrode shows superior data retention and program/erase performance that current CTF devices cannot achieve. The findings of this study can lead to new applications of graphene, not only for Flash memory devices but also for other high-performance and mass-producible electronic devices based on MOS structure which is the mainstream of the electronic device industry. PMID- 22059811 TI - Pig slaughtering procedures: Head-to-back stunning. AB - High voltage head-to-back electrical stunning can induce vertebral compression fractures, blood splash and poor meat quality in pigs. This experiment was designed to determine the optimum position of the rear electrode which would not only stun and kill pork and bacon weight pigs with a 1.3 A 50 Hz sinewave but would also produce a good carcass with desirable meat quality. Although there was a trend for less breaks to occur the further forward the rear electrode was positioned, there was no position which gave 100% cardiac fibrillation and an absence of breaks. The incidence of blood splash, muscle haemorrhages and the variations in meat colour were not related to electrode position and fell in the 'normal' range quoted by other workers. The severity and incidence of kicking after stunning was reduced the more caudal the electrode position. This was in direct contrast to the effect on compression fractures where a reduction was seen with the more rostral applications. PMID- 22059812 TI - Effect of ionizing radiation on unesterified tocopherols in fresh chicken breast muscle. AB - The effect of ionizing radiation on free tocopherols in chicken was determined Raw chicken breast muscle with skin and adipose tissue removed was subjected to gamma radiation from a (137)Cs source at 1, 2.25, 5.0, and 10.0 kGy. The chicken was packaged aerobically, and irradiated at 4 degrees C. Free tocopherols were extracted directly from the meat without a saponification step. The tocopherols were resolved using normal phase, high performance liquid chromatography by spectrophotofluorometric detection. Irradiation resulted in a significant linear decrease in alpha and gamma tocopherol with increasing dose levels. At 3 kGy, the maximum level approved by the FDA for poultry, a 15% reduction of free gamma tocopherol and a 30% reduction for free alpha tocopherol were observed. PMID- 22059813 TI - Classification of pig myofibres and assessment of post-mortem glycogen depletion according to fibre type by computerized image analysis. AB - A computer-aided method for muscle fibre type determination and qualitative analysis of glycogen at a cellular level is described. The operational system consists of a microscope, a CCD videocamera, an image analysis card, a colour monitor and a standard workstation computer (32 Mb central memory, 22 mips) running under the UNIX operating system. The programme was developed with 512 * 512 pixel images. Four main steps can be distinguished: digitization, network extraction, network matching and measurement of staining intensities. The data generated for each analysed fibre included, diameter, cross-sectional area, ATPase staining intensity and type. Ten minutes of batch processing and 36-41 min of interactive work were needed to analyse 200-300 fibres. Results have shown that this image analysis system can distinguish four types of myofibres denoted I, IIA, IIB and IIC, on the basis of myosin ATPase sensitivity at three preincubation pH values (4.10, 4.35 and 10.4). Preliminary results have also shown that the image analysis system can be used to measure post-mortem glycogen depletion according to fibre type. PMID- 22059814 TI - Effect of nitrate, nitrite and ascorbate on colour and colour stability of dry, fermented sausage prepared using 'back slopping'. AB - The effect of various levels of nitrite and nitrate, with and without ascorbate, in sausages prepared using 'back slopping' as inocluation, was investigated in three series of experiments. In all experiments, nitrite was rapidly depleted and nitrate formed. Nitrate was not used, probably because of the lack of (active?) micrococci in the starter sausage. Surface colour was found to be darker with increasing levels of nitrite. Irrespective of nitrate, colour stability was mainly promoted by residual ascorbate. The latter decreased with increasing nitrite levels. PMID- 22059815 TI - Effects of aqueous washings on colour and nutrient quality of mechanically deboned chicken meat. AB - Mechanically deboned chicken meat (MDCM) was washed with water, 0.5% NaCl or 0.5% NaHCO(3) solutions. Approximately 75.5% of the total hemoprotein pigments were removed by washing of MDCM with a sodium bicarbonate solution which resulted in the best colour improvements in the samples. Approximately 18.7% of total lipids were removed as a result of aqueous washing. The yield of proteins ranged from 56.5% after one washing with water to 43.4% after washing with water and then with a sodium bicarbonate solution. The Hunter L and a colour parameters of the samples correlated well with the total hemoproteins (correlation coefficients 0.984 and +0.947, respectively); corresponding correlation coefficient with the Hunter b value was only +0.693. PMID- 22059816 TI - Comparative action of cathepsins B and L on intramuscular collagen as assessed by differential scanning calorimetry. AB - Intramuscular beef collagen of different degrees of reticulation was treated with cathepsin L obtained from chicken liver and a commercial cathepsin B prepared from beef spleen. It was shown that, in the absence of calcium, both proteinases caused a decrease in the initial temperature of denaturation whereas the total enthalpy of denaturation was unaffected. Treatment with cathepsin B resulted in the appearance of a new peak of denaturation at a lower temperature (~ 44 degrees C), a change wholly comparable with that obtained previously when intramuscular beef collagen was treated with a collagenase from Clostridium histolyticum. There was no such change with cathepsin L. The addition of 20 mM CaCl(2) to the incubation buffer brought about a shift in the total enthalpy of denaturation when collagen was treated with cathepsin L; in contrast, no additional effect was observed in cathepsin B treatments. These findings led to the suggestion that cathepsins B and L have a different mode of action on collagen and that there may be a similarity in the mechanism of action between cathepsin B and the bacterial collagenase. PMID- 22059817 TI - Haematological and clinico-chemical profiles of barrows at the farm and at slaughter. AB - Haematological and clinico-chemical profiles of blood of healthy stress-resistant swine collected at the farm and at slaughter were determined to investigate whether values of blood variables can be used to establish stress. The values of most variables investigated showed highly significant changes. It is concluded that haematological and clinico-chemical values may be useful in studies to detect, quantify and reduce stress-provoking conditions in stress-resistant swine. PMID- 22059818 TI - The assessment of pre-slaughter and slaughter treatments of livestock by measurement of plasma constituents-A review of recent work. AB - The measurement of plasma constituents in a blood sample can provide information on the stress status of the animal. The interpretation of results obtained for constituents of blood samples collected at exsanguination must consider the effect of the slaughter process on the constituent. Both electrical and mechanical stunning methods can cause dramatic increases in catecholamine levels and minor increases in glucose levels. Thus, there are difficulties in the interpretation of catecholamine and, to a lesser extent, glucose, values in blood samples collected post-stunning. Cortisol levels appear to be unaffected by stunning methods and measurement of this constituent in post-slaughter blood samples has been used to assist in the evaluation of transport and abattoir treatments. Beta-hydroxybutyrate concentrations may assist in evaluating nutritional stress prior to slaughter while the limited evidence available suggests that beta-endorphin measurements will be of value in assessing pain and other stressors prior to slaughter. Adreno-corticotrophic hormone, calcium and magnesium, free fatty acids, glucose, lactate and thyroid hormones have all been used on occasions to assist in the evaluation of stress status. In some cases it was not possible to demonstrate a clear relationship between plasma constituents that indicate stress, and stress-related meat quality defects. PMID- 22059819 TI - Autoxidation of purified myoglobin from two bovine muscles. AB - To elucidate the behavioural differences between beef muscles from the viewpoint of colour stability, oxymyoglobin was extracted at 2 h post mortem, purified from two different muscles (longissimus lumborum (LL), stable and psoas major (PM), unstable) and the autoxidation rate was measured. Oxymyoglobin was isolated after separation from metmyoglobin by chromatography on DEAE-Sepharose and TSK SW 2000 columns, and its purity was controlled by electrophoresis and IEF. Over a wide range of pH values (5-9), temperatures (20-50 degrees C) and ionic strength (0 500 mM), no difference was noted between autoxidation rates of LL and PM oxymyoglobin extracted at 2 h post mortem. Conversely, when myoglobin was extracted at 192 h post mortem, the autoxidation rate of PM oxymyoglobin was higher than LL myoglobin, particularly at elevated temperatures. These differences in autoxidation rates after extraction of myoglobin at 2h and 192 h post mortem were not associated with differences in Ea (approximately 23 kcal/mol). PMID- 22059820 TI - Heme pigment content in meat as affected by the addition of curing agents. AB - The effects of curing agents on the content of heme pigments (HP) in meat were examined. Minced porcine skeletal muscle was treated with NaCl, NaNO(2) and sodium ascorbate (NaAsA), separately or in combination, and stored at 2-3 degrees C for 7 days. HP content decreased with increase in NaCl concentration and the decrease was about 50% and 80% at NaCl concentrations of 2% and 10%, respectively. Two percent NaCl prevented HP destruction, when previously mixed with 100 ppm NaNO(2) or 0.1% NaAsA. Although some decrease in HP content was noted following application of a mixture of NaCl, NaNO(2) and NaAsA, it was essentially the same as that of the control during 7 days of refrigerated storage. In a model solution containing the same curing agents as those applied to the meat. NaCl had no effect and myoglobin (Mb) content remained constant during storage. From the present results, endogenous muscle constituents appear to act in concert with NaCl to bring about a decrease in HP content. PMID- 22059821 TI - Marbling, intramuscular fat and meat colour of Dutch pork. AB - The amounts of intramuscular (i.m.) fat in the lean meat of the lumbar region of 21 slaughterpigs have been determined according to the Soxhlet method as a reference, and compared with those determined with the faster Foss-let procedure. These methods were highly correlated, over the lower range of fat concentrations (0.30-4.35%) studied. Although the Foss-Let values were on average slightly lower than the Soxhlet values, the Foss-Let procedure can be recommended for the determination of i.m. fat in pork. Furthermore, chemically determined i.m. fat was found to be significantly correlated with marbling. The sensory evaluations of pork colour were significantly correlated with each other and with the instrumentally determined colour lightness. PMID- 22059822 TI - A probe to measure GR in lamb carcasses at chain speed. AB - The GR (total tissue thickness at the twelfth rib, 110 mm from the midline) was measured with the AUS-MEAT sheep probe (ASP) on lamb carcasses at chain speed by an abattoir operator in two experiments, both at the same abattoir. In both experiments, GR was also measured on the carcass by an independent operator using a GR knife. For experiment 1, a total of 779 lamb carcasses were measured over four occasions and for experiment 2 data on 607 lamb carcasses were obtained on two occasions, twelve months after experiment 1. In both experiments, one operator measured the manual GR and a different operator used the ASP. A new version of the ASP was used in the second experiment. In only 30% of cases in experiment 1 did the operator probe at the correct rib, and in the majority of cases the thirteenth rib was used as the probing site. In only a small percentage of cases (2%) was the operator more than one rib away from the twelfth rib. In 67% of the cases for experiment 1, the operator probed at the correct site with respect to distance from the midline. Models were developed to describe the relationship between the manual and ASP GR measurements. In experiment 2, the amount of variation in manual GR explained by ASP measurements was greater than that in experiment 1 (R(2) = 0.80 compared with 0.72), and the accuracy of the estimates was significantly increased (+/- 1.54 mm compared with 2.31 mm). The better over-all performance of the ASP in the second experiments was indicated by the fact that for 90% of the sample the ASP measurements were within +/-2 mm of the manual GR measurements whereas, for experiment 1, the level was less than 70%. Measurement time (day), which could be described as an operator 'effect', was identified as an important factor influencing the accuracy of GR estimates but location of the probed site with respect to the GR site was not found important. The significance of operator training and monitoring is discussed on the basis of the results, as are the implications of the findings for objective purchasing systems. PMID- 22059823 TI - Use of electronic probes for classifying lamb carcasses. AB - Three commercially available electronic lamb carcass grading probes (Hennessy Grading Probe, AUS-Meat Sheep Probe, Swedish FTC Lamb Probe) and one developmental probe (Ruakura GR lamb probe) were assessed for accuracy and suitability for use on-line on the lamb dressing chain for objectively classifying lamb carcasses. GR is the total tissue thickness over the 12th rib taken at a distance 11 cm from the mid-line, used to define fatness in lamb carcass grading in New Zealand. Probe measurements were compared with manually measured GR (sometimes used at present) and Toland probe measurements (total tissue depth between the ribs) for accuracy of predicting both GR on the right side of the carcass and also carcass water (indicating muscle) and fat content. Probes were tested on six occasions, each having approximately 50 lambs. All probes combined with carcass weight accounted for over 70% of the variation (R(2)) of GR right, with GR left accounting for 92% of the variation of GR right. Inclusion of a quadratic probe term was not quite as useful as inclusion of carcass weight for predicting GR right. The three commercial electronic probes individually when combined with carcass weight could account for 36-49% of the variation in the percentage of water and fat in the carcass, with the manual GR probe (right) on the chilled carcass accounting for 55% of the variation in water and 58% of the variation in fat percentages. Chilled carcass measurements are expected to give better results than readings on hot carcasses. The use of a quadratic probe coefficient instead of carcass weight with the probe readings gave similar accuracy of prediction of carcass composition. There was little difference between the two sides in the accuracy of prediction. Small differences were found between regressions relating probe readings to GR and composition for the different probing occasions. The electronic probe results from this trial are consistent with overseas results where probes are in use for objectively grading the carcasses of meat animals. PMID- 22059824 TI - Quantification of beef myofibrillar proteins by SDS-PAGE. AB - A semi-quantitative determination of beef myofibrillar proteins using sodium, dodecyl sulphate polyacrylamide gel electrophoresis is described. Bovine serum albumin was used as internal standard. Results indicate a linear relationship between densitometric readings after staining with Coomassie brilliant blue R(250) and protein content. Recoveries of four pure proteins, loaded within a range of 0.5-4 MUg, were between 92 and 110%. Heating of beef myofibrillar protein samples during dissolution is shown to be unnecessary. The method allows the quantitative study of myofibrillar degradation during beef aging, without overlapping of troponin-T with tropomyosin bands. PMID- 22059825 TI - Basic chemical characteristics of fresh, non-packed and vacuum-packed sheep-tail and tail-fat stored frozen for different periods. AB - Fatty tails were obtained after the slaughter of Morkaraman sheep, which are a common breed of fatty-tailed sheep in Turkey. Fat obtained from sheep tails, (called tail-fat) is used either in fresh condition or after frozen storage. This fat is commonly used as a food source in many countries in which fat-tail sheep breeds are raised; but there has been no detailed research on fatty tails or the tail-fat. In this work some quality criteria such as water, fat and nitrogen content, 2-thiobarbituric acid and peroxide numbers, free fatty acids, melting point, iodine and saponification numbers were studied in sheep tails and sheep tail-fat, both in the fresh condition and after storage at -18 +/- 1 degrees C for up to 60 days. The effect of vacuum packaging versus storage in netting bags (no-protection, non-packed), was also determined. The fat content of the tails was around 94%. Thus, the tail is a concentrated fat source. Some quality criteria of the tail and the tail-fat were determined and are given in the text. Overall results indicated that both the tail and the tail-fat can be effectively used in various types of food and food processing, especially after performing some technological and refining processing. If the fatty tail has to be stored, it should be vacuum packed and stored frozen. At -18 degrees C, vacuum-packed tail samples could be stored around 45 days, but in the netting bags, this storage period should not exceed 30 days. PMID- 22059826 TI - Localization of metmyoglobin-reducing enzyme (NADH-cytochrome b(5) reductase) system components in bovine skeletal muscle. AB - Localization of metmyoglobin-reducing enzyme system components (NADH-cytochrome b(5) reductase, cytochrome b(5) outer mitochondrial membrane cytochrome b) was demonstrated in bovine skeletal muscle by immunohistochemical techniques. Both NADH-cytochrome b(5) reductase and OM cytochrome b were located in red fibers. However, localization of cytochrome b(5) did not show a definite difference between fiber types. Using an immunoblotting technique. NADH-cytochrome b(5) reductase was found predominantly in the mitochondrial fraction, but it was also detected at lower levels in the microsomal fraction. OM cytochrome b was found predominantly in the mitochondrial fraction, but cytochrome b(5) was detected only in the microsomal fraction. The results from this study, along with previous work about the localization of myoglobin in muscle, suggest that NADH-cytochrome b(5) reductase reduces metmyoglobin by using OM cytochrome b at the mitochondrial surface and, in part, by using cytochrome b(5) at the sarcoplasmic reticulum. PMID- 22059827 TI - Optimum conditions for beef carcass chilling. AB - Optimum chilling schemes for a two- or three-stage chilling system were developed using a validated heat and mass transfer model and a pattern search algorithm. The optimization was performed for the ambient temperature during each stage for an air velocity of 0.5 m/s and 90% relative humidity. The experiments were conducted to evaluate the effect of the optimum conditions on beef quality after ageing. PMID- 22059828 TI - Grinding as a method of meat texture evaluation. AB - An electric grinder equipped with a torque/speed sensor was used to evaluate maximum grinding torque (T(max)) and total energy (TE) necessary to grind 150 g of uncooked meat. Texture profile analysis (TPA), relaxation and cutting tests were carried out and sample compositions were also determined. The degree of dependence between grinding, TPA, relaxation, cutting parameters and sample composition was checked. Results showed that grinding parameters (T(max) and TE) correlated better with TPA, relaxation and cutting parameters than with composition. In particular correlation coefficient of -0.92, -0.92 and 0.97 were obtained, respectively, between T(max) and relaxation percentage (%R), T(max) and destructuring coefficient at 25% conmpression (De(25)) and between T(max) and maximum cutting force (F(c)). PMID- 22059829 TI - Plasma and muscle cortisol measurements as indicators of meat quality and stress in pigs. AB - Post-slaughter blood samples and muscle samples were collected from pigs slaughtered at the completion of a live-animal performance trial. There were two lines of pigs in which the halothane allele (n) was segregating. The lines were a lean line selected for rapid lean growth and an unselected fat line. There were homozygous normal (NN), homozygous halothane positive (nn) and heterozygous (Nn) genotypes in both lnes. Cortisol was measured in the plasma of the blood samples and in muscle juice obtained by high-speed centrifugation. Meat quality was assessed using pH, colour, fibre-optic probe, drip loss and cure yield measurements. Plasma cortisol concentrations in the fat line were significantly (P < 0.05) greater than thosein the lean line but concentrations did not differ significantly for the three halothane genotypes. Carcasses classified as dark, firm and dry (DFD) had significantly (P < 0.05) greater muscle cortisol concentrations than those classified as normal. Plasma and muscle cortisol concentrations of carcases classified as pale, soft and exudative (PSE) did not differ significantly from those classified as normal. Correlations between muscle cortisol and meat quality attributes were generally highly significant (r = 0.31 to r = 0.51, P < 0.001) There was a highly significant correlation (r = 0.73, P < 0.0001) between plasma and muscle cortisol concentrations. PMID- 22059830 TI - Effectson carcass weight and meat quality of pigs dehaired by scalding or singering post-mortem. AB - Two experiments were designed to compare the effects of two pig dehairing techniques. In the first experiment, 120 pigs were slaughtered in the same abattoir in five weekly sereis. One half of each series was dehaired by singeing (the usual technique in this abattoir), while the other half was dehaired in a scalding-dehairing combination. In the second experiment, 48 pigs were slaughtered in two series, one-half of each series in an abattoir practising singeing, the other half in an abattoir practising scalding. Temperature and pH were measured 30 min after slaughter in the longissimus lumborum. Meat quality was assessed the day after slaughter in various muscles. One ham was cured and cooked, while the other one was processed by dry-curing. In both experiments, carcass weights and yields were noticeably higher after singeing. Hams were heavier in singed carcasses, but their proportions in the carcasses were little or not at all affected by the dehairing technique. Proportions of loins, shoulders and bellies were similar with both dehairing techniques. The dehairing technique affected neither temperature nor rate of post-mortem pH fall. Meat quality as assessed on fresh meat was slightly better in singed carcasses. Weights of cooked ham and dry ham per side were higher in singed carcasses, due to the higher initial ham weight, but processing yields were not affected by the dehairing technique. PMID- 22059831 TI - Effect of dietary supplementation of vitamin E on pig meat quality. AB - The effect of vitamin E on pig meat quality was investigated using British Landrace (NN and nn), Landrace * Large White (NN and Nn) and Pietrain (nn) pigs. Daily dietary supplementation of 500 mg vitamin E/kg diet for 46 days could reduce drip loss in unfrozen longissimus thoracis (LT) by 45% and 54% in Nn and NN pigs, respectively. In PSE-prone Landrace * Large White Nn pigs, daily supplementation of 1000 mg vitamin E/kg diet for the same period could significantly (P < 0.001) reduce excess release of Ca(2+) and prevent the formation of PSE carcasses, evaluated from both biopsy and post- mortem LT samples. Experimental evidence from erythrocyte fragility and water-holding capacity of biopsy LT samples suggested that vitamin E improved pig meat quality by its ability to stabilize membranes. Stabilization of membrane integrity in isolated mitochondria of LT by vitamin E was associated with inhibition of phospholipase A(2) activity. PMID- 22059832 TI - The effects of spray-chilling on carcass mass loss and surface associated bacteriology. AB - The effect of spray-chilling on carcass mass loss and bacteriology was tested in this trial. The spray-chill treatment consisted of intermittent spraying of carcasses for either 60 or 120 s every 15 min, for 10, 14 or 17 h. The 17 h/120 s spray-chill treatment gave the highest and 10 h/60 s the lowest moisture savings after 18 h of chilling. Due to insufficient drying time between the end of spraying (17 h) and the end of chilling (18 h) the carcass sides of the 17 h/60 s and 120 s treatments appeared pale and wet; this was not the case with the other treatments. Regarding microbial analyses, the results indicated that, except for the 17 h/20 s spray-chill treatment, the mean total and Enterobacteriaceae counts of the spray-chill treatments were similar to their respective control groups (conventionally chilled). The mean total and Enterobacteriaceae counts of the 17 h/20 s spray-chill treatments increased, while those of the controls decreased. PMID- 22059833 TI - Physico-chemical and processing quality of porcine M. longissimus dorsi frozen at different temperatures. AB - Longissimus dorsi muscle from six pigs (24 h post-mortem) was cut into portions of similar size and shape (c. 700 g) and vacuum-packed in polyfilm. The muscle specimens were divided into three samples, one frozen at -20 degrees C, another at -80 degrees C and the third served as the control (not frozen). The meat sample frozen at -80 degrees C was transferred to the -20 degrees C freezer. After one month, both frozen pork samples were thawed at -2 degrees C and drip loss (%) was measured. Hunter colour, metmyoglobin (MetMb) formation (%), water holding capacity (WHC), TBA value, transmission value (TM) and myofibril fragmentation were also determined. There was no significant difference in drip loss for the two frozen samples. No MetMb formation could be detected and Hunter values were basically the same for all three samples. WHC, TBA value and TM were essentially the same for all three samples. TBA value was quite low for each frozen sample, indicating that lipid oxidation did not occur during freezing. Histological examination of both frozen samples indicated inter- and intracellular ice crystal formation at -20 degrees C, and intracellular ice at 80 degrees C, the extent being less than at -20 degrees C. At -20 degrees C, ice crystals were larger and muscle fibre diameter smaller than for the control or 80 degrees C sample. Myofibril fragmentation in both frozen samples was significantly higher than in the control. Pork sausage was prepared from all three samples by adding 2% NaCl and 100 ppm NaNO(2). Cooking loss and colour forming ratios were essentially the same. The sausage sample made from the -20 degrees C frozen meat was harder than that of the other two samples according to rheological measurement. PMID- 22059834 TI - The basal toughness of unaged lamb. AB - Identification of the commencement of aging in relation to the rigor process was determined on lamb loin muscles by injecting a zinc-TRIS solution, which inhibits meat aging, into the muscle over the period when the pH was falling. Aging was evaluated by measuring the tenderness of cooked meat samples using a MIRINZ tenderometer. When zinc was injected into muscle above pH 6.5, the sarcomeres shortened and the cooked meat had an average shear force of 19 kgF (shear force is the force required to shear through at 1 cm cross-section sample). When sinc was injected into the muscle at pH values below 6.5 the sarcomeres did not shorten, and down to the ultimate pH, the shear force remained at approximately 15 kfF. Aging did not take place pre-rigor. The same relationships occurred for electrically stimulated muscle. The data indicate that the basal shear-force value of lamb loin prior to aging, i.e. the basal toughness level, is 15 kgF. PMID- 22059835 TI - Variations in meat quality in live halothane heterozygotes identified by biopsy samples of M. longissimus dorsi. AB - The meat quality of halothane heterozygotes (Nn) was investigated using British Landrace (n = 18) and Landrace * Large White pigs (n = 67). Normal and PSE meat were identified in both breeds using M. longissimus dorsi (LD). In Landrace * Large White Nn pigs, the potential meat quality identified using small biopsy LD samples (500 mg) showed a wide spectrum in water-holding capacity (WHC), ranging from normal (43%) to PSE (57%). Predictions of meat quality in live pigs were confirmed from post-mortem assessments of LD samples based on pH(1) and fibre optic probe measurements. Our results show that Nn pigs have the propensity to produce a higher proportion of PSE than normal carcasses. The predictive meat quality test performed on small biopsy LD samples offers an opportunity not currently available to the pig industry, to select Nn pigs with the potential to produce pork of superior WHC. PMID- 22059836 TI - Functionality of high and low voltage electrically stimulated beef chilled under moderate and rapid chilling regimes. AB - Chuck muscles from 24 beef carcasses electrically stimulated (ES) with either high or low voltage, or a combination of both, and submitted to conventional or rapid chilling regimes were used in a model system study (pH, salt-solubloe protein extraction, emulsifying capacity) and in frank-further fabrication and analysis (yield, color, texture). Glycolytic rates measured in the loin had no effects on the functional parameters or on the quality of frankfurters. The ultimate pH values of unstimulated carcasses remained higher than in any ES carcasses, and led to higher protein extraction (P <= 0.05). However, ES had no further influence on the emulsifying capacity or on frankfurter yield and quality parameters independently of the voltage used (P > 0.05). Chilling regimes had no influence on the functional parameters of the model system but slightly influenced the yield and chewiness of the frankfurters (P <= 0.05). Therefore, the use of any type of ES in combination with either conventional (Canadian) or more rapid chilling is unlikely to have commercial significance on the yield or quality of frankfurters. PMID- 22059837 TI - Additives in finnish sausges and other meat products. AB - Additives such as sodium nitrate, potassium nitrate, sodium nitrite, phosphates and sodium chloride in sausages and various meat products were examined. Nitrate, nitrite and phosphate concentrations were below the maximum permitted levels, but most of the samples examined contained large amounts of sodium chloride and were thus "extra salted". Sausage factories should lower the salt concentrations in their products. PMID- 22059838 TI - Food safety 1993 Food Research Institute, Department of Food Microbiology and Toxicology, University of Wisconsin. Published by Marcel Dekker, New York, US$165.00. PMID- 22059839 TI - Psychosocial aspects of haemophilia: a systematic review of methodologies and findings. AB - Psychosocial factors have a significant impact on quality of life for patients with chronic diseases such as haemophilia. Interventions to support the psychosocial needs of patients and their families, such as offering information and assistance, clarifying doubts, and teaching coping strategies to minimize the impact of disabilities, may help to maximize patient outcomes and improve quality of life for their families. The aim of this study was to evaluate the current literature on psychosocial aspects of haemophilia. Literature searches were performed using the PubMed database to identify studies evaluating psychosocial stressors in persons with haemophilia. Articles pertaining to the HIV epidemic were excluded from the analysis, as were those published before 1997. The literature reviews identified 24 studies, covering a range of different populations, generally with small cohorts (n < 100). Most studies were questionnaire based, with almost no overlap in terms of the instruments used. Only one study combined questionnaire techniques with qualitative methods. Except for two European studies, all publications reported data from a single country. Overall, studies tended to show that quality of life is reduced in persons with haemophilia, with a potential impact on education and employment, particularly when prophylactic treatment is not available. Carrier status in women may have a psychosocial impact and affect reproductive choices. Data on psychosocial aspects of the haemophilia life cycle are lacking in the published literature, along with data from developing countries. There is a need for more international, multifaceted research to explore and quantify the social and psychological aspects of life with haemophilia. PMID- 22059840 TI - Face the noise: embodied responses to nonverbal vocalizations of discrete emotions. AB - Extensive prior research has shown that the perception of an emotional facial expression automatically elicits a corresponding facial expression in the observer. Theories of embodied emotion, however, suggest that such reactions might also occur across expressive channels, because simulation is based on integrated motoric and affective representations of that emotion. In the present studies, we examined this idea by focusing on facial and experiential reactions to nonverbal emotion vocalizations. In Studies 1 and 2, we showed that both hearing and reproducing vocalizations of anger, disgust, happiness, and sadness resulted in specific facial behaviors, as well as congruent self-reported emotions (Study 2). In Studies 3 and 4, we showed that the inhibition of congruent facial actions impaired listeners' processing of emotion vocalizations (Study 3), as well as their experiences of a concordant subjective state (Study 4). Results support the idea that cross-channel simulations of others' states serve facilitative functions similar to more strict imitations of observed expressive behavior, suggesting flexibility in the motoric and affective systems involved in emotion processing and interpersonal emotion transfer. We discuss implications for embodiment research and the social consequences of expressing and matching emotions across nonverbal channels. PMID- 22059841 TI - Do you believe in atheists? Distrust is central to anti-atheist prejudice. AB - Recent polls indicate that atheists are among the least liked people in areas with religious majorities (i.e., in most of the world). The sociofunctional approach to prejudice, combined with a cultural evolutionary theory of religion's effects on cooperation, suggest that anti-atheist prejudice is particularly motivated by distrust. Consistent with this theoretical framework, a broad sample of American adults revealed that distrust characterized anti-atheist prejudice but not anti-gay prejudice (Study 1). In subsequent studies, distrust of atheists generalized even to participants from more liberal, secular populations. A description of a criminally untrustworthy individual was seen as comparably representative of atheists and rapists but not representative of Christians, Muslims, Jewish people, feminists, or homosexuals (Studies 2-4). In addition, results were consistent with the hypothesis that the relationship between belief in God and atheist distrust was fully mediated by the belief that people behave better if they feel that God is watching them (Study 4). In implicit measures, participants strongly associated atheists with distrust, and belief in God was more strongly associated with implicit distrust of atheists than with implicit dislike of atheists (Study 5). Finally, atheists were systematically socially excluded only in high-trust domains; belief in God, but not authoritarianism, predicted this discriminatory decision-making against atheists in high trust domains (Study 6). These 6 studies are the first to systematically explore the social psychological underpinnings of anti-atheist prejudice, and converge to indicate the centrality of distrust in this phenomenon. PMID- 22059842 TI - Seeing isn't believing: the effect of intergroup exposure on children's essentialist beliefs about ethnic categories. AB - Adults and children seem to essentialize certain social categories. Three studies investigated whether, and how, exposure to ethnic diversity affects this bias. Participants were 516 kindergarten, 2nd grade, and 6th grade Israeli Jewish and Arab children attending regular (mono-cultural) or integrated schools. Study 1 revealed that exposure increased the salience of ethnicity, especially for Jewish children. Study 2 showed no differences among groups at kindergarten regarding the relevance of recalling a story character's ethnicity, but by 2nd grade, Jewish children attending integrated schools were the most likely to mention such information. Finally, Study 3 revealed that while all kindergarteners started off at a similar level of essentialism towards ethnicity, exposure affected Arab, but especially Jewish, children's essentialist beliefs. Moreover, there were negative correlations between the salience of and essentialism towards ethnicity. Thus, interethnic exposure alleviated children's essentialist bias towards ethnicity and did so via making children aware of, rather than blind to, ethnic categories. PMID- 22059844 TI - Seeing failure in your life: Imagery perspective determines whether self-esteem shapes reactions to recalled and imagined failure. AB - The present research reveals that when it comes to recalling and imagining failure in one's life, changing how one looks at the event can change its impact on well-being; however, the nature of the effect depends on an aspect of one's self-concept, namely, self-esteem. Five studies measured or manipulated the visual perspective (internal first-person vs. external third-person) individuals used to mentally image recalled or imagined personal failures. It has been proposed that imagery perspective determines whether people's reactions to an event are shaped bottom-up by concrete features of the event (first-person) or top-down by their self-concept (third-person; L. K. Libby & R. P. Eibach, 2011b). Evidence suggests that differences in the self-concepts of individuals with low and high self-esteem (LSEs and HSEs) are responsible for self-esteem differences in reaction to failure, leading LSEs to have more negative thoughts and feelings about themselves (e.g., M. H. Kernis, J. Brockner, & B. S. Frankel, 1989). Thus, the authors predicted, and found, that low self-esteem was associated with greater overgeneralization--operationalized as negativity in accessible self knowledge and feelings of shame--only when participants had pictured failure from the third-person perspective and not from the first-person. Further, picturing failure from the third-person, rather than first-person, perspective, increased shame and the negativity of accessible knowledge among LSEs, whereas it decreased shame among HSEs. Results help to distinguish between different theoretical accounts of how imagery perspective functions and have implications for the study of top-down and bottom-up influences on self-judgment and emotion, as well as for the role of perspective and abstraction in coping. PMID- 22059843 TI - Subjective well-being and adaptation to life events: a meta-analysis. AB - Previous research has shown that major life events can have short- and long-term effects on subjective well-being (SWB). The present meta-analysis examines (a) whether life events have different effects on affective and cognitive well-being and (b) how the rate of adaptation varies across different life events. Longitudinal data from 188 publications (313 samples, N = 65,911) were integrated to describe the reaction and adaptation to 4 family events (marriage, divorce, bereavement, childbirth) and 4 work events (unemployment, reemployment, retirement, relocation/migration). The findings show that life events have very different effects on affective and cognitive well-being and that for most events the effects of life events on cognitive well-being are stronger and more consistent across samples. Different life events differ in their effects on SWB, but these effects are not a function of the alleged desirability of events. The results are discussed with respect to their theoretical implications, and recommendations for future studies on adaptation are given. PMID- 22059845 TI - Construal level mind-sets moderate self- and social stereotyping. AB - Construal level theory suggests that events and objects can be represented at either a higher, more abstract level involving consideration of superordinate goals, desirability, global processing, and broad categorizations or a lower, more concrete level involving consideration of subordinate goals, feasibility, local processing, and narrow categorizations. Analogously, social targets (including the self) can be represented more broadly, as members of a group, or more narrowly, as individuals. Because abstract construals induce a similarity focus, they were predicted to increase the perceived fit between social targets and a salient social category. Accordingly, placing individuals into a more abstract construal mind-set via an unrelated task increased the activation and use of stereotypes of salient social groups, stereotype-consistent trait ratings of the self, group identification, and stereotype-consistent performance relative to more concrete construal mind-sets. Thus, nonsocial contextual influences (construal level mind-sets) affect stereotyping of self and others. PMID- 22059846 TI - On the perpetuation of ignorance: system dependence, system justification, and the motivated avoidance of sociopolitical information. AB - How do people cope when they feel uninformed or unable to understand important social issues, such as the environment, energy concerns, or the economy? Do they seek out information, or do they simply ignore the threatening issue at hand? One would intuitively expect that a lack of knowledge would motivate an increased, unbiased search for information, thereby facilitating participation and engagement in these issues-especially when they are consequential, pressing, and self-relevant. However, there appears to be a discrepancy between the importance/self-relevance of social issues and people's willingness to engage with and learn about them. Leveraging the literature on system justification theory (Jost & Banaji, 1994), the authors hypothesized that, rather than motivating an increased search for information, a lack of knowledge about a specific sociopolitical issue will (a) foster feelings of dependence on the government, which will (b) increase system justification and government trust, which will (c) increase desires to avoid learning about the relevant issue when information is negative or when information valence is unknown. In other words, the authors suggest that ignorance-as a function of the system justifying tendencies it may activate-may, ironically, breed more ignorance. In the contexts of energy, environmental, and economic issues, the authors present 5 studies that (a) provide evidence for this specific psychological chain (i.e., ignorance about an issue -> dependence -> government trust -> avoidance of information about that issue); (b) shed light on the role of threat and motivation in driving the second and third links in this chain; and (c) illustrate the unfortunate consequences of this process for individual action in those contexts that may need it most. PMID- 22059847 TI - In perfect harmony: synchronizing the self to activated social categories. AB - The self-concept is one of the main organizing constructs in the behavioral sciences because it influences how people interpret their environment, the choices they make, whether and how they initiate action, and the pursuit of specific goals. Because belonging to social groups and feeling interconnected is critical to human survival, the authors propose that people spontaneously change their working self-concept so that they are more similar to salient social categories. Specifically, 4 studies investigated whether activating a variety of social categories (i.e., jocks, hippies, the overweight, Blacks, and Asians) increased associations between the self and the target category. Whereas Studies 1 and 2 focused on associations between stereotypic traits and the self, Studies 3 and 4 examined self-perceptions and self-categorizations, respectively. The results provide consistent evidence that following social category priming, people synchronized the self to the activated category. Furthermore, the findings indicate that factors that influence category activation, such as social goals, and factors that induce a focus on the interconnectedness of the self, such as an interdependent vs. independent self-construal, can impact this process. The implications of changes to the working self-concept for intergroup relations are discussed. PMID- 22059848 TI - More than a body: mind perception and the nature of objectification. AB - According to models of objectification, viewing someone as a body induces de mentalization, stripping away their psychological traits. Here evidence is presented for an alternative account, where a body focus does not diminish the attribution of all mental capacities but, instead, leads perceivers to infer a different kind of mind. Drawing on the distinction in mind perception between agency and experience, it is found that focusing on someone's body reduces perceptions of agency (self-control and action) but increases perceptions of experience (emotion and sensation). These effects were found when comparing targets represented by both revealing versus nonrevealing pictures (Experiments 1, 3, and 4) or by simply directing attention toward physical characteristics (Experiment 2). The effect of a body focus on mind perception also influenced moral intuitions, with those represented as a body seen to be less morally responsible (i.e., lesser moral agents) but more sensitive to harm (i.e., greater moral patients; Experiments 5 and 6). These effects suggest that a body focus does not cause objectification per se but, instead, leads to a redistribution of perceived mind. PMID- 22059849 TI - Visual perspective influences the use of metacognitive information in temporal comparisons. AB - Four studies test the proposition that when people look back to past selves as a means of gauging current status, the visual perspective they assume determines the kind of information that they consider in making their judgments of change. In this way, visual perspective, coupled with the kind of change for which people are looking, determines how much change is perceived. The studies demonstrate that in the first-person perspective, experiential information is weighted more heavily than content information, whereas in the third-person perspective, the converse is true. In addition, the effects of perceived change on behavior are revealed, such that greater perceived positive change is associated with behaviors that are congruent with that change, whereas greater perceived negative change is associated with behaviors that are incongruent with that change. Theoretical implications, as well as implications for behavioral interventions, are discussed. PMID- 22059850 TI - Short-chain fatty acids induce pro-inflammatory cytokine production alone and in combination with toll-like receptor ligands. AB - PROBLEM: Short-chain fatty acids (SCFAs), produced at relatively high levels by anaerobic bacteria in bacterial vaginosis (BV), are believed to be anti inflammatory. BV, a common alteration in the genital microbiota associated with increased susceptibility to HIV infection, is characterized by increased levels of both pro-inflammatory cytokines and SCFAs. We investigated how SCFAs alone or together with Toll-like receptor (TLR) ligands affected pro-inflammatory cytokine secretion. METHOD OF STUDY: Cytokines were measured by ELISA. Flow was used for phenotyping and reactive oxygen species (ROS) measurement. RESULTS: Short-chain fatty acids, at 20 mM, induced interleukin (IL)-8, IL-6, and IL-1beta release, while lower levels (0.02-2 mM) did not induce cytokine secretion. Levels >20 mM were toxic to cells. Interestingly, lower levels of SCFAs significantly enhanced TLR2 ligand- and TLR7 ligand-induced production of IL-8 and TNFalpha in a time- and dose-dependent manner, but had little effect on lipopolysaccharide-induced cytokine release. SCFAs mediated their effects on pro-inflammatory cytokine production at least in part by inducing the generation of ROS. CONCLUSION: Our data suggest that SCFAs, especially when combined with specific TLR ligands, contribute to a pro-inflammatory milieu in the lower genital tract and help further our understanding of how BV affects susceptibility to microbial infections. PMID- 22059851 TI - Hydrophilic Cu9S5 nanocrystals: a photothermal agent with a 25.7% heat conversion efficiency for photothermal ablation of cancer cells in vivo. AB - Photothermal ablation (PTA) therapy has a great potential to revolutionize conventional therapeutic approaches for cancers, but it has been limited by difficulties in obtaining biocompatible photothermal agents that have low cost, small size (<100 nm), and high photothermal conversion efficiency. Herein, we have developed hydrophilic plate-like Cu(9)S(5) nanocrystals (NCs, a mean size of ~70 nm * 13 nm) as a new photothermal agent, which are synthesized by combining a thermal decomposition and ligand exchange route. The aqueous dispersion of as synthesized Cu(9)S(5) NCs exhibits an enhanced absorption (e.g., ~1.2 * 10(9) M( 1) cm(-1) at 980 nm) with the increase of wavelength in near-infrared (NIR) region, which should be attributed to localized surface plasmon resonances (SPR) arising from p-type carriers. The exposure of the aqueous dispersion of Cu(9)S(5) NCs (40 ppm) to 980 nm laser with a power density of 0.51 W/cm(2) can elevate its temperature by 15.1 degrees C in 7 min; a 980 nm laser heat conversion efficiency reaches as high as 25.7%, which is higher than that of the as synthesized Au nanorods (23.7% from 980 nm laser) and the recently reported Cu(2 x)Se NCs (22% from 808 nm laser). Importantly, under the irradiation of 980 nm laser with the conservative and safe power density over a short period (~10 min), cancer cells in vivo can be efficiently killed by the photothermal effects of the Cu(9)S(5) NCs. The present finding demonstrates the promising application of the Cu(9)S(5) NCs as an ideal photothermal agent in the PTA of in vivo tumor tissues. PMID- 22059853 TI - Schisandrin B, attenuates cisplatin-induced oxidative stress, genotoxicity and neurotoxicity through modulating NF-kappaB pathway in mice. AB - This study aimed to investigate the potential beneficial effect of an antioxidant lignan, Schisandrin B (Sch B), against cisplatin (cDDP) induced oxidative stress mediated geno- and neuro-toxicities. A dose of 10 mg/kg cDDP induced considerable genotoxicity in mice, and Sch B treatment attenuated the cDDP-induced DNA damage as assessed by the comet assay in the brain. The frequency of micro-nucleated erythrocyte production in bone marrow was also significantly reduced by Sch B treatment in cDDP-treated mice. In neurobehavioral studies, Sch B significantly prevented the memory deficits induced by cDDP, and had an anxiolytic effect in the elevated plus maze task. Sch B treatment significantly attenuated lipid peroxidation, acetylcholinesterase activity and nitrite levels induced by cDDP. Furthermore, Sch B effectively inhibited NF-kappaB and p53 activation, and cleaved caspase-3 expression in cDDP-treated mice. Hence, Sch B with potent antioxidant and neuro-protective property with no mutagenic activity would be beneficial complementary food factor against cDDP induced oxidative stress. PMID- 22059854 TI - Deep vein thrombosis/pulmonary embolism: a survey of self-reported prevention practices among hospitals. AB - Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major causes of preventable complications for hospitalized patients worldwide. The National Quality Forum (NQF) recommends that all patients be assessed for DVT/PE risk upon admission, periodically thereafter, and receive evidence-based pharmacologic prophylaxis. Objectives of this study were to capture information about hospital practices related to detection, prevention, and treatment of DVT/PE and to explore relationships between hospital characteristics and an applicable patient safety indicator (PSI) #12 postoperative DVT/PE. Two study phases were conducted in the south-central region of the United States. First, a survey tailored to gather information about the study objectives from subject matter experts was administered, and then, using the subject matter expert results, an online survey of performance improvement professionals was deployed. Using this 5-point Likert scale online survey, respondents at each hospital reflected their DVT/PE prevention practices approach and status. Results provided insight for trends in hospital-based DVT/PE prevention practice, associated hospital characteristics, relationship among domains of prevention practice, and how electronic DVT/PE order sets related to DVT/PE outcomes. Relationship of all these characteristics to hospital overall PSI #12 postoperative DVT/PE rates were compared. Future study and survey development recommendations were discussed. PMID- 22059855 TI - Acute treatment with kerosene damages the dermal barrier and alters the distribution of topically applied benzo(a)pyrene in mice. AB - The dermal route is important in many occupational exposures. Some materials may reduce the barrier function of the skin to enhance absorption and effect on internal organs. We have reported previously that kerosene cleaning following treatment with used engine oil increased DNA adduct levels in the lungs of mice compared with animals treated with used oil alone. To investigate what other physiological parameters might be affected by kerosene, we conducted in vitro and in vivo measurements of skin barrier function. We also topically applied (3)H BAP(100 nM in 25 MUL acetone) and washed half the mice with 25 MUL kerosene 1 hr after carcinogen application. Groups of four mice were euthanized from 1 to 72 hr after treatment. Skin, lungs, and livers were harvested from each animal and stored separately. Kerosene application reduced the barrier function of the skin in vitro beyond the effect of the acetone vehicle and the vehicle plus BAP. In vivo studies indicated that kerosene treatment reduced the barrier function at 4 and 8 hr post application and that the barrier function recovered at 24 hr after a single treatment. The fraction of the radiolabel remaining in the skin of animals treated with (3)H-BAP and washed with kerosene was significantly less than those not washed, beginning at 24 hr (p< 0.05). Fractional distribution to the lungs and livers of these animals became significantly elevated at this time. Kerosene treatment compromises dermal barrier function and the ability of the skin to retain water, enhances carcinogen absorption, and alters organ distribution. This appears to contribute to the increase in BAP DNA adducts we reported earlier. PMID- 22059856 TI - Identifying barriers to mental health system improvements: an examination of community participation in assertive community treatment programs. AB - BACKGROUND: Integrating the best available evidence into program standards is essential if system-wide improvements in the delivery of community-based mental health services are to be achieved. Since the beginning of the Assertive Community Treatment (ACT) program movement, program standards have included a role for the community. In particular, ACT program standards have sought to ensure that members of the local community are involved in governance and that former clients participate in service delivery as "Peer Support Specialists". This paper reports on the extent to which ACT program standards related to community participation have been implemented and identifies barriers to full compliance. METHODS: Qualitative and quantitative data were collected through a telephone survey of ACT Program Coordinators in Ontario, Canada, using a census sample of the existing 66 ACT programs. A thematic approach to content analysis was used to analyze respondents' qualitative comments. Quantitative data were analyzed using SPSS 16.0 and included means, frequencies, independent t-tests and Pearson Correlations. RESULTS: An 85% response rate was achieved. Of the 33 program standards, the two that received the lowest perceived compliance ratings were the two standards directly concerning community participation. Specifically, the standard to have a functioning Community Advisory Body and the standard requiring the inclusion of a Peer Support Specialist. The three major themes that emerged from the survey data with respect to the barriers to fully implementing the Community Advisory Body were: external issues; standard related issues; and, organizational/structural related issues. The three major themes concerning barriers to implementing the Peer Support Specialist role were: human resource related issues; organizational/structural related issues; and, standard related issues. CONCLUSIONS: The reasons for low compliance of ACT programs with community participation standards are complex and are tied to structural and human resources barriers (both internal and external to the ACT programs) as well as to the requirements of the standards themselves. In order for improvements to the mental health system to be achieved there is a need to identify and address these barriers. Failure to do so will result in less than optimal client, family and economic efficiency outcomes. PMID- 22059857 TI - Bi-auricular myxoma associated with atrioventricular dissociation in an 18-year old boy: a case report. AB - Primary cardiac tumours are rarely found and have an incidence of 0.3% in all open-heart surgeries. Among those, approximately 70% are myxomas, most of them in the left atrium. The reported incidence of cardiac tumours in autopsy series is 0.001-0.28%. Right atrial myxomas are uncommon, but when present they often originate from the interatrial septum, and conduction disturbances are rarely noted as an accompanying feature in this condition. We report the case of an 18 year-old boy with a myxoma in both left and right atrium associated with atrioventricular dissociation. PMID- 22059858 TI - Ocular pharmacokinetics profile of different indomethacin topical formulations. AB - PURPOSE: This study evaluated the ocular pharmacokinetics of indomethacin following topical administration of two different formulations present in the market. METHODS: Rabbits received a multiple topical instillation (30 MUL) of indomethacin ophthalmic suspension containing hydroxypropylmethylcellulose (IND HPMC; IndomTM Alfa-Intes) or indomethacin ophthalmic solution with hydroxypropyl beta-cyclodextrin (IND-CD; IndocollirioTM Bausch & Lomb). Aqueous humor, vitreous humor, and retina were collected from animals at fixed time intervals after dosing. Indomethacin ocular levels were measured by liquid chromatography mass spectrometry (LC-MS/MS), and the pharmacokinetic parameters--peak drug concentration (C(max)), time to peak value (T(max)), and area under the concentration-time curve between 0 and 240 min (AUC(0-240))--were determined. All of the animals were treated according to the Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use of Animals in Ophthalmic and Vision Research. RESULTS: Peak concentrations of indomethacin in aqueous and vitreous were achieved within 30 min and 60 min after a single instillation of IND-HPMC and IND-CD, respectively. Retinal T(max) was 30 min and 120 min in the IND-HPMC-treated group and the IND-CD-treated group, respectively. Higher levels of indomethacin were found in retina after IND-HPMC administration compared to IND-CD (AUC(0-240) 272.9 ng/g per min vs. AUC(0-240) 73.5 ng/g/min, respectively; P<0.01). Also in the aqueous and vitreous, the drug levels were statistically higher (P<0.01) in the IND-HPMC group in comparison with the IND-CD group (AUC(0 240) 2039 ng/mL per min vs. AUC(0-240) 427.3 ng/mL per min, AUC(0-240) 53.8 ng/mL per min vs. AUC(0-240) 12.5 ng/mL per min, respectively). The highest drug levels in the ocular tissues were found following IND-HPMC administration compared with IND-CD (retina: C(max) 73.7+/-6.4 ng/g vs. 25.5+/-1.73 ng/g; aqueous: C(max) 952+/-6.8 ng/mL vs. 163+/-4.1 ng/mL; vitreous C(max) 31+/-3.5 ng/mL vs. 6.37+/ 3.6 ng/mL). CONCLUSIONS: IND-HPMC treatment demonstrates a nonclinical ocular pharmacokinetic profile of indomethacin characterized by higher concentrations of drug in ocular tissues (4.7-, 4.3- and 3.7-fold higher in aqueous, vitreous, and retina, respectively) compared to the ND-CD-treated group. Taken together, these data seem to indicate that IND-HPMC formulation has good ocular distribution reaching relevant indomethacin levels in the back of the eye, and suggest that this formulation may be very useful for clinicians to manage retinal conditions. PMID- 22059859 TI - A rare case of recurrent ovarian cancer presenting as a round ligament metastasis. AB - We report a rare case of recurrent ovarian cancer presenting as a round ligament metastasis. A 44-year-old woman presented with a lower abdominal mass. Computed tomography showed a pelvic mass. Primary surgery was performed. A histopathological examination showed an ovarian serous adenocarcinoma of Stage IIIb. The patient received 6 cycles of paclitaxel and carboplatin. Almost 2 years after the initial operation, the patient noticed a left inguinal mass. Computed tomography showed a left inguinal mass, 18 mm in size. An excisional biopsy was performed and the tumor was found to originate in the left round ligament. A histopathological examination showed serous adenocarcinoma and there was no evidence of lymph node tissue. Recurrence of ovarian cancer in the round ligament is extremely rare. This unique case suggests, however, that the round ligament in rare cases may be a recurrence site for ovarian cancer, and that accurate differentiation including confirmation by diagnostic imaging and excisional biopsy, is necessary for a definitive pathological diagnosis. PMID- 22059860 TI - Neurolaw: Differential brain activity for black and white faces predicts damage awards in hypothetical employment discrimination cases. AB - Currently, potential jurors' racial biases are measured by explicit questioning- a poor measure because people often hide their views to adhere to social norms, and people have implicit views they are not consciously aware of. In this experiment, we investigated whether two alternative methods of measuring racial bias--a standard black/white, good/bad implicit association test (IAT) and neural activity, measured by fMRI, in response to seeing faces of black and white individuals--could predict how much money subjects would award Black victims in hypothetical employment discrimination cases. IAT scores failed to predict how much money subjects awarded victims. However, in right inferior parietal lobule (BA 40) and in right superior/middle frontal gyrus (BA 9/10)--which have both previously been implicated in measuring biases and implicit preferences--the difference in neural activity between when subjects viewed black faces paired with neutral adjectives and when subjects viewed white faces paired with neutral adjectives was positively correlated with the amount of money the subjects awarded victims. This suggests that brain activity measures racial bias with more practical validity, at least in this situation and with our sample size, than a common behavioral measure (the IAT). PMID- 22059861 TI - Abdominal surgery for chronic constipation. PMID- 22059862 TI - Commentary on Murad-Regadas et al. PMID- 22059866 TI - Stereoselective synthesis of C-substituted morpholine derivatives using reductive etherification reaction: total synthesis of chelonin C. AB - A general strategy is developed for the stereoselective synthesis of C substituted morpholine derivatives using intramolecular reductive etherification reaction. The method is extended to the first stereoselective total synthesis of (+/-)-chelonin C. PMID- 22059867 TI - Oral health condition of French elderly and risk of dementia: a longitudinal cohort study. AB - OBJECTIVES: Oral condition could be associated with cognitive impairment, but this is not yet well documented. We therefore hypothesized that people with poor oral condition would be more at risk to develop dementia. The objective of this study thus was to describe the oral condition of French community-dwelling elderly persons and to assess its relationship with the occurrence of dementia. METHODS: Oral examination was conducted on a sample of individuals aged 66-80 years followed-up prospectively for screening of dementia over 15 years in Gironde, France. Univariate and multivariate analyses of the risk of dementia were performed using a Cox proportional hazard model with delayed entry. RESULTS: Data from 405 individuals were analyzed; 45.4% men; median age at baseline: 70 years [interquartile range (IQR): 68-75]. The median number of decayed, missing, and filled teeth was 18 (IQR: 13-24) and was higher in women (median: 20 versus 17, P = 0.004) and in persons with lower school level (median: 21 versus 17, P = 0.003). Among 348 persons with sextant eligible for periodontal assessment, 2/3 required periodontal care: 5.2% had bleeding observed, 44.8% calculus, 17.8% 4-5 mm pockets, and 2.9%>= 6 mm pockets. The incidence of dementia during a median follow-up of 10 years (IQR: 6.5-13.7) was 19 per 1000 person-years. The adjusted hazard ratio for a number of missing teeth >= 11 (median) on the risk of dementia was 1.13 (95% confidence interval, CI = [0.60-2.12]) in people with higher education (n = 312) and 0.30 (CI = 0.11-0.79) in persons with lower school level (n = 93) (P for modification effect = 0.0002). CONCLUSIONS: Having eleven or more missing teeth seemed to be associated with a lower risk of dementia in people with lower education possibly owing to the suppression of source of chronic inflammation. PMID- 22059868 TI - On the behavior of dew drops. AB - It may be observed that, when dew drops form, although they may be positioned randomly on flat leaves, they tend to accumulate at the pointed ends of thin, slightly conical growths. We discuss here the basic physics leading to this phenomenon. PMID- 22059869 TI - Confocal laser scanning microscopy, optical coherence tomography and transonychial water loss for in vivo investigation of nails. AB - BACKGROUND: Nail disorders can be diagnostically challenging to the dermatologist. Noninvasive methods might help to avoid nail biopsies. More knowledge of the typical features of healthy nails with these techniques is needed for comparison with nail diseases. OBJECTIVES: To describe the typical morphology of healthy nails in optical coherence tomography (OCT) and confocal laser scanning microscopy (CLSM) and to examine the influence of exposure to water on OCT features, nail thickness as well as on transonychial water loss (TOWL) before and after a hand bath. Material and methods In the first part healthy nail plates were investigated with OCT and CLSM. The thickness of layers as well as structural details were defined. Secondly, in a prospective study 30 healthy volunteers conducted 10 hand baths with water within a 2-week period. Measurements of nail thickness and signal intensity by OCT as well as of the TOWL were performed over time. RESULTS: In OCT the unaffected nail plate appears as a band-like, layered structure, yet with some individual differences. In addition, CLSM is able to display single corneocytes and the integrity of their borders. Exposure to water led to a transient rise of TOWL and in nail thickness. CONCLUSIONS: OCT, CLSM and TOWL offer valuable noninvasive diagnostic tools for the examination of nails. Using CLSM, microscopic features like integrity of single corneocytes can be investigated. OCT allows determination of nail plate thickness and both OCT and TOWL measurements are able to detect short-term effects after exposure to water. PMID- 22059870 TI - The effect of low voltage and high voltageelectrical stimulation on pork quality. AB - Carcasses from 36 Large White gilts, 70-80 kg live weight, were randomly allocated to three experimental groups. Pigs in the first group were electrically stimulated with low voltage during bleeding (85v, 14Hz for 64 s) and split before cooling. The left sides were rapidly chilled in air at -15 degrees C for 75 min and then at 1 degrees C until 24 h post-slaughter; right sides were chilled conventionally in air at 1 degrees C for 24 h. In the second group, two different treatments were used 20 min post-slaughter: left sides were stimulated with low voltage, and right sides with high voltage (700 v, 12.5 Hz for 90 s). Both sets of sides were chilled rapidly. Carcasses from the third group were not stimulated, and sides chilled either rapidly or conventionally. Drip loss, colour and texture were measured in M. longissimus thoracis et lumborum at 3 and 10 days post-slaughter. At 3 days post-slaughter the high voltage, treatment gave meat which was the most tender, was not pale and lost no more drip than unstimulated controls. Low voltage stimulation during bleeding gave meat which was 18% more tender than the unstimulated controls, but the improvement in tenderness was not as great as the 28% achieved with high voltage. Unexpectedly, low voltage stimulation applied 20 min after slaughter, was almost as effective in improving tenderness (by 17%) as low voltage applied during bleeding. Tenderness improved from 3 days to 10 days in all stimulated samples, but not in unstimulated controls. The results suggest a degree of coldtoughening in the latter, even with conventional chilling, and a positive effect of electrical stimulation on tenderness, independent of its protective action against cold-shortening. PMID- 22059871 TI - Improving pork quality by electricalstimulation or pelvic suspension ofcarcasses. AB - This investigation compared the separate and combined effects on meat quality of electrical stimulation (ES) and pelvic suspension of pig carcasses chilled rapidly or conventionally. Sides from 80 pigs, 80-90 kg live weight, were allocated to one of four treatments followed by either conventional chilling (1 degrees C for 24 h) or rapid chilling (-20 degrees C for 2-3 h, before 1 degrees C until 24 h post-slaughter). The four treatments were: Achilles suspended, with and without high voltage ES, and pelvic suspended, with and without ES. The quality attributes: pH, colour and opacity, drip loss, instrumental and sensory texture were measured in M. longissimus thoracis et lumborum, at 10 days post slaughter. Rapid chilling reduced the evaporative weight loss by 0.5% There were no significant effects of treatment on colour or opacity, although ES samples were slightly paler. Drip loss was also slightly greater with ES, particularly when combined with pelvic suspension, but in no case was the meat classified as PSE. Instrumental measurements of 'texture showed improved tenderness from both ES and pelvic suspension, even after 10 days ageing. The improvement was less pronounced when ES and pelvic suspension were combined Taste panelling confirmed that samples treated by ES or pelvic suspension, separately or combined, were significantly more tender than samples from non-ES, Achilles hung sides. ES and pelvic suspension were equally effective in improving the tenderness of pork loin. Pelvic suspension did not suffer the disadvantage of increased drip loss that occurred with ES in this study. PMID- 22059872 TI - The effect of chilling, electrical stimulation and conditioning on pork eating quality. AB - The effect of three different post-slaughter treatments and subsequent conditioning times on the eating quality of pork was studied, using a total of 72 pigs (80-90 kg live wt). The treatments were: (A) holding in air at > 10 degrees C for 3 h, followed by chilling in air at 1 degrees C; (B) chilling in air at 1 degrees C; (C) high voltage electrical stimulation (ES) at 20 min post-slaughter, followed by Treatment B. The quality attributes were measured in M. longissimus thoracis et lumborum (LTL) and in M. semimembranosus (Sm). There was little difference in cooling rate between the three treatments; the major effect on quality came from the use of ES in Treatment C. ES reduced pH at 45 min by approximately 0.3 units, and achieved pH values at 3 h post-slaughter of 5.64 (LTL) and 5.87 (Sm) but did not produce PSE meat. Drip losses were generally low, but were slightly higher with Treatment C. By all three instrumental texture parameters, LTL from Treatment C was significantly more tender than from A and B at 4, 7 and 12 days post-slaughter, suggesting that either some cold toughening with A and B was overcome by ES in treatment C or that ES had some other beneficial action. Conditioning at 1 degrees C improved the tenderness of LTL from 4 to 7 days and further to 12 days. Taste panelling of loin chops and Sm roasts confirmed that Treatment C gave significantly more tender meat than A and B, and that ageing from 4 to 7 days and further to 12 days significantly improved tenderness. High voltage electrical stimulation at 20 min post-slaughter followed by cooling in air at 1 degrees C (Treatment C) produced loin muscle which was more tender at 4 days than at 12 days with the other treatments. PMID- 22059873 TI - Changes in sugars during storage of sausages. AB - The shelf-life of fresh British sausages is determined by the production of off odours and colour changes due to microflora in the sausage. From work on meat, and in pure culture, it is known that the carbon source of the principal spoilage microorganism (Brochothrix thermosphacta) can affect its metabolism and change the nature of the secondary metabolic products. The sugar content of sausages was determined immediately after manufacture and during storage at 4 degrees C. Reducing-sugar content (measured by dinitrophenol phenolate, or DNP) increased in the first few days after manufacture, then decreased. The apparent increase in reducing sugar was due to hydrolysis of rusk components (oligo- or polysaccharides) either by meat or microbial enzymes. Thus, the amounts and types of sugar available for microbial growth change during storage. The effect of sulphite on the sugar assay and on sugar utilisation was also measured. Sulphite affected the DNP reducing sugar assay and caused a small increase in the absorbance at 510 nm. Addition of sulphite to the sausage formulation also caused some changes in the reducing-sugar content during storage at 4 degrees C. PMID- 22059874 TI - Measuring water-holding capacity in pork musculature with a tensiometer. AB - The water-holding capacity (WHC) of post-mortem porcine musculature is an important quality trait, and it is desirable for the industry to assess its variations ,for purposes of evaluating and processing pork products. There are several procedures to accurately determine WHC, but most are either too slow, too expensive or are impractical for commercial application. Since WHC is also important when examining the characteristics of soil, scientists routinely use an instrument called a tensiometer for this measurement. Therefore, we explored the potential application of this technique for assessing WHC in post-rigor pork muscle. The cost, potential speed and invasive application of the tensiometer in muscle were attractive characteristics. A sample (29) of pork loins, representing considerable variation in WHC were used to test the applicability of a commercial tensiometer. When tensiometer measurements were compared to 48 h drip loss, the results indicated the tensiometer could accurately detect the variations in free fluids expressed in muscle and that the procedure could be applied quickly and invasively without altering the commercial value of the product. However, particles (primarily protein and fat) in the muscle fluid became imbedded in the pores of the tensiometer ceramic tip, thus impairing the repeated use of the instrument. A plastic filter was developed to prevent clogging, but it could not be molded adequately to permit rapid insertion and removal for on-line measurements of WHC. Therefore, despite the various desirable features of the tensiometer, it failed to meet some requirements considered essential for further testing as a potential commercial, on-line procedure. First, the clogging problem must be resolved The study also indicated that the filter paper test would be more appropriate than the tensiometer for use in field tests to predict WHC when limited numbers of samples were to be tested. PMID- 22059875 TI - The influence of porcine growth hormone on muscle fibre characteristics, metabolic potential and meat quality. AB - Treatment of lean female pigs with porcine growth hormone (placebo or 80 MUg pGH per kg body weight per day) for 6 weeks from 50 kg to 86 kg body weight did not change the frequency and the percentage area of muscle fibre types (ST, FTa and FTb fibres) and muscle capillarity of M. longissimus dorsi, M. gluteus medius and M. psoas major. The mean fibre cross-sectional area increased 5.3%, albeit nonsignificantly, corresponding to a 6.6% increase in carcass meat. The muscles contained slightly less dry matter and protein, and the lipid content of M. longissimus dorsi decreased 19% after pGH treatment. In the backfat the fatty acid composition changed towards a higher ratio of polyunsaturated to saturated fatty acids. The pH(u) of M. longissimus dorsi was unaltered, while the pH(45) was reduced by pGH. The muscle glycogen level and the activity of lactate dehydrogenase (LDH), citrate synthetase (CS), and 3-OH-acyl-CoA-dehydrogenase (HAD) of M. longissimus dorsi were unchanged by pGH. The haem pigment, shear force, sarcomere length and eating quality of loin chops, were unaffected by pGH treatment. The results show that pGH treatment did not change the muscle characteristics in a way that affects the meat quality of M. longissimus dorsi in lean female pigs. PMID- 22059876 TI - The effects of residual oxygen concentration and temperature on the degradation of the colour of beef packaged under oxygen-depleted atmospheres. AB - Samples of beef longissimus dorsi (LD), approximately 5 * 5 * 1 cm, were packaged in pairs under 10 litre volumes of N(2) or CO(2) containing O(2) at concentrations between 100 and 1000 ppm. The packaged samples were stored at temperatures of 5, 1, 0 or -1.5 degrees C, for times between 4 and 48 h. Samples of beef psoas major (PM) were packaged under N(2) or CO(2) containing O(2) at between 100 and 600 ppm, and stored at -1.5 degrees C for 24 or 48 h. After storage, each sample was assessed for colour deterioration and discoloration, and for the fraction of metmyoglobin in the surface pigment. The results obtained with N(2) and CO(2) atmospheres were similar. The colours of all LD samples had deteriorated after 4 h storage at 5 or 1 degrees C, although the degree of deterioration increased with increasing O(2) concentration. All LD samples stored for 12 h at 5 or 1 degrees C were extensively discoloured, with metmyoglobin fractions generally exceeding 60%, but those stored at -1.5 degrees C for 48 h or less, under O(2) concentrations <= 400 ppm had undergraded colours. The colours of some LD samples stored at -1.5 degrees C under about 600 ppm of O(2) were also undergraded, but the colours of samples stored under 800 or 1000 ppm had deteriorated by 24 h. The colours of LD samples stored at 0 degrees C under > 200 ppm had deteriorated after 24 h storage, and the colours of samples stored under 100 ppm O(2) had deteriorated after 48 h storage. All PM samples were wholly discoloured after storage at -1.5 degrees C. Evidently, the colour of beef muscle of high colour stability is resistant to degradation by atmospheres containing < 600 ppm of O(2) when the meat is stored at sub-zero temperatures, but not when the storage temperature is at or above 0 degrees C. Beef muscle of low colour stability, such as the PM, will discolour at all low concentrations of O(2) irrespective of the storage temperature. PMID- 22059877 TI - Post-weaning evolution of muscle energy metabolism and related physico-chemical traits in the rabbit. AB - Metabolic differentiation in muscles was analysed in 50 rabbits of New Zealand White breed (strain INRA 1077) slaughtered at 28, 42, 56, 70 or 84 days. The activity of enzymes representing the glycolytic (fructose 1,6-diP aldolase) and the oxidative (NADP-isocitrate dehydrogenase) (ICDH) energy metabolism pathways, and two related physico-chemical traits, haem pigment content and ultimate pH, were estimated in semimembranosus proprius + soleus, psoas major and longissimus lumborum muscles. Aldolase activity was lowest in semimbranosus proprius + soleus, which are pure betaR and the most precociously developed muscles, whereas haem pigment content and ultimate pH were highest; however, physico-chemical traits changed moderately during growth. In the psoas major (pure alphaW) and in the longissimus lumborum (mixed muscle), which develop later, aldolase activity increased until the 56th and 70th day respectively. The decrease in ICDH activity lasted longer, especially in the longissimus lumborum muscle. A significant negative relationship between aldolase activity and ultimate pH may explain why the ultimate pH decreased during fattening. PMID- 22059878 TI - A comparison of some metabolitesin skeletal muscle of different halothane sensitivity withmeat quality traits of pigs using a capillary isotachophoresis technique. AB - Isotachophoretic (ITP) measurements were made on biopsy samples from live muscle M. longissimus lumborum and carcasses of pigs. Two experiments were performed. In Experiment 1, the methodological aspects of ITP measurements from skeletal muscle, were studied. In Experiment 2, ITP measurements on muscle and carcass samples were made. The muscle and carcass samples were obtained by shot or spring loaded biopsy from the Longissimus lumborum muscle of 30 Belgium Landrace * Duroc pigs, of which 10 were halothane-positive. The pigs were slaughtered by electro stunning and manguination at approximately 105 kg body l. w. The potential meat quality in live pigs and after slaughter using small biopsy samples of M. longissimus lumborum was also determined. The experimental results show that ITP (mainly inosinemonophosphate and lactate) and meat quality data (water-holding capacity test, pH and R value) can differentiate halo thane-positive from halothane-negative pigs. Out results confirmed previous results which showed that the water-holding capacity test defined as fluid volume', pH and R value measurements on biopsy samples can also predict the potential meat quality in live pigs. PMID- 22059879 TI - Inter-animal variation in the biological characteristics of muscle tissue in male limousin cattle. AB - The biochemical, metabolic and contractile characteristics of semitendinosus (ST) and longissimus thoracicus (LT) muscles were studied in 147 male Limousin cattle. The animals, which were slaughtered at 16 months, were the offspring of 15 different sires. Weight gain and carcass tissue composition (proportion of muscle and adipose tissue) were also measured. The biochemical characteristics of the two muscles studied had coefficients of variation between 13 and 30% markedly higher than for proximate characteristics of the carcass, in which coefficients were all lower than 18%. There were significant differences between the two muscles: ST had a higher protein/DNA ratio and greater lactate dehydrogenase (LDH) activity than LT, also a lower isocitrate dehydrogenase (ICDH) activity and lower slow myosin heavy chain (MHCI) content. The percentage of MHC 1 was positively correlated with ICDH activity and negatively with LDH activity and protein/DNA ratio. These muscle characteristics were also correlated with weight gain: animals with greater weight gain had a higher protein/DNA ratio and lower oxidative activity, with differences in the level of significance of the correlations according to muscles. Selection of animals on the basis of muscle growth may therefore be a means of improving the quality of meat. PMID- 22059881 TI - Editorial. PMID- 22059880 TI - Meat composition in genetically selected a control cattle from a serial slaughter experiment. AB - Young bulls from an Angus yearling-weight selection herd (ASl) and from the contemporary control herd (ACO), differing in average slaughter weight by 16.8%, were allocated for slaughter on one or six occasions between 7.5 and 25 months of age. The M. longissimus lumborum from the left side of each animal was measured for cholesterol, fatty acid composition, and protein, fat and ash contents in both raw and cooked samples; the pH and tenderness were also recorded. All meat was generally lean, averaging 4% fat in raw samples and 2.4% fat in cooked samples. There was a trend, though not significant, for a slightly lower percentage of fat at a fixed age in raw and cooked meat from the AS] herd than from the A CO herd. There were no significant selection effects on cholesterol content or fatty acid content, in either raw or cooked meat samples. The pH was significantly, higher in meat from the ASl than the A CO herd, although the difference was small (0.11 units), and there were no significant herd differences in tenderness. Overall, the herd effects on chemical composition and tenderness were very small and unlikely to be detected by consumers. PMID- 22059882 TI - 5-Lipoxygenase-activating protein (FLAP) inhibitors. Part 4: development of 3-[3 tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2 ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor. AB - The potent 5-lipoxygenase-activating protein (FLAP) inhibitor 3-[3-tert butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy) 1H-indol-2-yl]-2,2-dimethylpropionic acid 11cc is described (AM803, now GSK2190915). Building upon AM103 (1) (Hutchinson et al. J. Med Chem.2009, 52, 5803-5815; Stock et al. Bioorg. Med. Chem. Lett. 2010, 20, 213-217; Stock et al. Bioorg. Med. Chem. Lett.2010, 20, 4598-4601), SAR studies centering around the pyridine moiety led to the discovery of compounds that exhibit significantly increased potency in a human whole blood assay measuring LTB(4) inhibition with longer drug preincubation times (15 min vs 5 h). Further studies identified 11cc with a potency of 2.9 nM in FLAP binding, an IC(50) of 76 nM for inhibition of LTB(4) in human blood (5 h incubation) and excellent preclinical toxicology and pharmacokinetics in rat and dog. 11cc also demonstrated an extended pharmacodynamic effect in a rodent bronchoalveolar lavage (BAL) model. This compound has successfully completed phase 1 clinical studies in healthy volunteers and is currently undergoing phase 2 trials in asthmatic patients. PMID- 22059883 TI - Evolution of iridium-based molecular catalysts during water oxidation with ceric ammonium nitrate. AB - Organometallic iridium complexes have been reported as water oxidation catalysts (WOCs) in the presence of ceric ammonium nitrate (CAN). One challenge for all WOCs regardless of the metal used is stability. Here we provide evidence for extensive modification of many Ir-based WOCs even after exposure to only 5 or 15 equiv of Ce(IV) (whereas typically 100-10000 equiv are employed during WOC testing). We also show formation of Ir-rich nanoparticles (likely IrO(x)) even in the first 20 min of reaction, associated with a Ce matrix. A combination of UV vis and NMR spectroscopy, scanning transmission electron microscopy, and powder X ray diffraction is used. Even simple IrCl(3) is an excellent catalyst. Our results point to the pitfalls of studying Ir WOCs using CAN. PMID- 22059884 TI - Social networking for adolescents with severe haemophilia. AB - Access to modern treatments allows adolescents with haemophilia to manage their haemophilia at home, with improved treatment outcomes and quality of life, but has reduced peer support and the potential for experiential learning from older peers. Social networking, aided by modern communication technologies, may offer health benefits through peer support. We sought to assess whether or not disease specific social networking could benefit adolescents with severe haemophilia. A total of 150 adolescents (aged 10-18) with severe haemophilia A or B from 11 UK treatment centres or those who had attended focus groups to explore the potential for a social network designed specifically for their use were surveyed. Teenage boys with severe haemophilia in the UK who responded to an online and paper questionnaire (n = 47; 31% response rate) rarely knew of or socialized with others with haemophilia outside their families. Two-thirds of respondents said they would like to meet others. For 70% of boys, parents were the major source of information about haemophilia, yet more than half said they often had trouble finding answers to their questions. These boys frequently used online social networks to chat with friends. Adolescents with severe haemophilia frequently have limited contact with others and many wish to have greater contact. They may benefit from peer support and experiential learning gained through online social networking. The SixVibe restricted access social network is to be launched in 2011. It includes features designed to promote and facilitate the development of peer-to peer disease management skills for adolescents with severe haemophilia. PMID- 22059885 TI - The two-component histidine kinases DrkA and SlnA are required for in vivo growth in the human pathogen Penicillium marneffei. AB - In order to cause disease fungal pathogens must be capable of evading or tolerating the host immune defence system. One commonly utilized evasion mechanism is the ability to continually reside within macrophages of the innate immune system and survive subsequent phagocytic destruction. For intracellular growth to occur, fungal pathogens which typically grow in a filamentous hyphal form in the environment must be able to switch growth to a unicellular yeast growth form in a process known as dimorphic switching. The cue to undergo dimorphic switching relies on the recognition of, and response to, the intracellular host environment. Two-component signalling systems are utilized by eukaryotes to sense and respond to changes in the external environment. This study has investigated the role of the hybrid histidine kinase components encoded by drkA and slnA, in the dimorphic pathogen Penicillium marneffei. Both SlnA and DrkA are required for stress adaptation but are uniquely required for different aspects of asexual development, hyphal morphogenesis and cell wall integrity. Importantly, slnA and drkA are both essential for the generation of yeast cells in vivo, with slnA required for the germination of conidia and drkA required for dimorphic switching during macrophage infection. PMID- 22059886 TI - A parallel method for enumerating amino acid compositions and masses of all theoretical peptides. AB - BACKGROUND: Enumeration of all theoretically possible amino acid compositions is an important problem in several proteomics workflows, including peptide mass fingerprinting, mass defect labeling, mass defect filtering, and de novo peptide sequencing. Because of the high computational complexity of this task, reported methods for peptide enumeration were restricted to cover limited mass ranges (below 2 kDa). In addition, implementation details of these methods as well as their computational performance have not been provided. The increasing availability of parallel (multi-core) computers in all fields of research makes the development of parallel methods for peptide enumeration a timely topic. RESULTS: We describe a parallel method for enumerating all amino acid compositions up to a given length. We present recursive procedures which are at the core of the method, and show that a single task of enumeration of all peptide compositions can be divided into smaller subtasks that can be executed in parallel. The computational complexity of the subtasks is compared with the computational complexity of the whole task. Pseudocodes of processes (a master and workers) that are used to execute the enumerating procedure in parallel are given. We present computational times for our method executed on a computer cluster with 12 Intel Xeon X5650 CPUs (72 cores) running Windows HPC Server. Our method has been implemented as a 32- and 64-bit Windows application using Microsoft Visual C++ and the Message Passing Interface. It is available for download at https://ispace.utmb.edu/users/rgsadygo/Proteomics/ParallelMethod. CONCLUSION: We describe implementation of a parallel method for generating mass distributions of all theoretically possible amino acid compositions. PMID- 22059887 TI - Tenderisation of lamb meat: Effect of rapid postmortem temperature drop on muscle conditioning and aging. AB - Lamb Longissimus dorsi muscles were excised from carcasses of 9-12 kg and 16-20 kg weight and brought to internal temperatures of either 0 degrees C, 4 degrees C, 10 degrees C, 15 degrees C, 20 degrees C or 36 degrees C within 3-4h post mortem. After rigor completion they were allowed to age at 4 degrees C for 7 days. Sensory panel scores obtained on the first day of post-rigor aging showed that meat from heavier animals was tougher than that of lighter ones at any temperature. In all cases aging for 7 days had a marked tenderising effect which was similar at all studied temperatures, and greater in heavier animals. Tenderness was also dependent on the temperature at conditioning, as shortening caused by either high or low temperature resulted in meat toughening. The sole and surprising exception to this fact was, however, the high sensory scores obtained in 0 degrees C experiments, even though shortening occurred as expected. In fact, a more intense proteolysis was evident in this case, which was already apparent on the first day of aging. The effect of a rapid drop of muscle temperature to 0 degrees C on the fast and intense proteolysis, capable of even overcoming toughness due to cold shortening, was explained by the higher pH and the dramatic increase of the sarcoplasmic Ca(++) level induced early post mortem by chilling and which might result in the activation of calpain. PMID- 22059888 TI - Effect of mixing male sex types of cattle on their meat quality and stress related parameters. AB - Mixing of male cattle prior to slaughter results in increased physical activity, particularly homosexual behaviour, teasing and mounting. The number of mounts exhibited during the initial 4 h after mixing showed statistically significant correlations with serum enzyme levels at slaughter, pHu, glycolytic metabolites, colour and pigment proportions of M. longissumus dorsi at 48 h post-mortem. The amount of teasing showed significant correlations with pHu, glycolytic metabolites, colour and pigment proportions. The aggressive behaviour, pushing and butting, occurred only as retaliative acts and did not seem to affect meat quality. Among the male types used in this study, the vasectomised bulls were found to be more homosexually hyperactive and thus produced the highest number of dark-cutting carcasses, suggesting that the vasectomised bulls are more prone to dark-cutting due to mounting that occurs during pre-slaughter mixing. PMID- 22059889 TI - Performance and carcass characteristics of bulls as influenced by exogenous hormones. AB - One-hundred and forty-four weanling bulls of Angus (A, n = 48), Simmental x Hereford (SH, n = 8) and Simmental (S, n = 48) breeding were either castrated, left intact, left intact and implanted with Ralgro or left intact and implanted with Synovex S. Cattle were slaughtered after 190, 246 or 315 days of high-energy feeding. The right side of each carcass was electrically stimulated. Steers were inferior to intact treatments for most performance and carcass cutability traits, but steers were superior in marbling and lean quality (P < 0.05). There were no differences (P>0.05) in dressing percentage or ribeye area per 100 kg of carcass weight among treatments. Relative to intact bulls, Ralgro and Synovex S increased carcass masculinity. Implanted intact treatments did not differ from nonimplanted intacts for feed conversion, average daily gain, yield grade characteristics, percent longissimus dorsi chemical fat and 9-10dash11th rib composition (P >0.05). PMID- 22059890 TI - Palatability of beef from bulls administered exogenous hormones. AB - One-hundred and forty four weanling bulls of Angus (A, n = 48), Simmental x Hereford (SH, n = 48) and Simmental (S, n = 48) breeding were either castrated, left intact, left intact and implanted with Ralgro or left intact and implanted with Synovex S. Cattle were slaughtered after either 190, 246 or 315 days of high energy feeding, and the right side of each carcass was electrically stimulated. Sensory analysis was conducted on longissimus dorsi steaks after 5 days aging and Warner-Bratzler shear force (WBS) was measured after 5, 10 and 15 days aging. Steers had lower (P < 0.05) WBS and more desirable sensory panel scores for juiciness, ease of fragmentation, amount of connective tissue and overall tenderness than all intact treatments. The implanting of weanling bulls with synthetic steroid hormone compounds did not make a practical improvement in beef tenderness. PMID- 22059891 TI - Consumer attitudes to selected lamb cuts. AB - Analysis of responses by 151 people to five questions about meat and, in particular, lamb, showed that consumption of lamb on a weekly basis varied widely between consumers. There was some evidence that people who produce their own meat have a higher consumption of lamb than those who do not. A clear preference for either traditional or alternative lamb cuts according to the sex of the respondent was not found. Overall 60% of respondents preferred bone-in as opposed to bone-out leg, 72% preferred midloin to valentine chops and 73% preferred bone out as opposed to bone-in forequarters. PMID- 22059892 TI - Microbiological effects of acid decontamination of pork carcasses at various locations in processing. AB - The microbiological effect of hot (55 degrees C), 1% (v/v) lactic acid sprayed on the surface of pork carcasses (n = 36) immediately after dehairing, after evisceration (immediately before chilling) or at both locations in slaughter/ processing was determined. Mean aerobic plate counts (APCs) of all acid-treated carcass surfaces were numerically lower than those of control carcasses: however, in most cases these reductions were not statistically significant (P>0.05). All samples tested for the presence of Salmonella and Listeria were negative. No significant differences in sensory characteristics or microbiological counts were evident for acid-treated and control carcass loins that were vacuum packaged and stored 0-14 days post-fabrication. Mean pH value and scores of sensory attributes such as lean color, surface discoloration, fat color, overall appearance and off odor of chops from acid-treated carcasses were not significantly and/or consistently different from chops of comparable control carcasses. The role of bacterial attachment to pork skin and its effect on the decontaminating efficiency of lactic acid are discussed. PMID- 22059893 TI - The microbiology of sheep carcasses processed in a modern Indian abattoir. AB - A study has been conducted on the microbiology of sheep carcasses processed in a modern abattoir. The data revealed that careful handling at the different stages of processing of sheep reduced the level of microbial contamination of carcasses. Processing steps such as evisceration and washing did not increase the microbial counts on the carcass surface. Sources of microbial contamination in the abattoir were examined. It was observed that skin, floor washings, intestinal contents and gambrels were the major sources of microbial contamination. Seasonality did not have any effect on the microbial contamination of carcasses. The study revealed that total plate counts in 86.6% of the carcasses ranged between 3.0 4.9log/cm(2). The counts of coliforms, staphylococci, enterococci and psychrotrophs were low. Pathogens such as Salmonella were not detected. The microbial counts were well within the generally acceptable levels. These findings demonstrated hygienic handling of carcasses. Shoulder and neck are the critical points for microbiological sampling as these sites showed higher microbial counts. Micrococcus and Staphylococcus predominated among microorganisms associated with carcasses. It was noted that differences occurred in microbial types of carcasses processed in tropical and temperate climates. The data generated in a model facility procided useful information for improving meat handling practices. PMID- 22059894 TI - The microbiological and technological properties of bruised beef. AB - Currently, bruised beef is condemned under meat hygiene regulations within Australia. The aim of this study was to determine whether bruised beef was microbiologically and technologically sound and therefore suitable for use in processed meat products. Paired samples of bruised and unbruised beef from sides processed through three abattoirs were collected over an 18 month period, and analysed for a range of microbiological, chemical and physical parameters. There were no differences in the microbiological loads or growth rates of micro organisms, and only small differences in the compositional and processing properties between the two tissues. There appears to be no microbiological or technological reason for the condemnation of bruised beef. PMID- 22059895 TI - Fatty acid composition of subcutaneous and intramuscular adipose tissues and M. longissimus dorsi of Wagyu cattle. AB - Three experiments were conducted to document the fatty acid composition of tissues from purebred Wagyu cattle from Japan and North American crossbred Wagyu. In experiment 1, subcutaneous (s.c.) adipose tissues (n = 23) were obtained from Japanese cattle representing the five Japanese fat quality grades. The monounsaturated:saturated fatty acid ratio (MUFA:SFA) was greatest in fat quality grade 5 samples (2.57) and least in the fat quality grade 3 samples (2.08; P < 0.05). In experiment 2, M. longissimus dorsi and the associated intramuscular (i.m.) and s.c. adipose tissues were obtained from carcasses of Wagyu crossbred steers (1/2-7/8) raised in the USA. Fatty acid composition varied among depots, but the MUFA:SFA ratio in s.c. adipose tissue (1.46) was not different from values reported for other breeds of cattle. In experiment 3, samples of M. longissimus dorsi ribsteaks were obtained from three regions in Japan. Samples from the Gunma region had the greatest (P < 0.05) MUFA:SFA ratio (2.10), relative to samples from the Kagoshima (1.82) and Miyazaki (1.65) regions. The data indicate that beef from purebred Wagyu cattle raised in Japan is enriched in monounsaturated fatty acids, and that the degree of enrichment depends upon the region of Japan from which the samples were obtained. PMID- 22059896 TI - Determination of the antioxidative activity of substituted 5-aminopyrimidines. AB - The aminopyrimidine structural motif can be found in diverse biologically active compounds. This study aimed to describe the antioxidant activity of a series of di- and tri-substituted 5-aminopyrimidines using in vitro (TEAC, LPO) and cell based assays. 2,4,6-trisubstituted 5-aminopyrimidines displayed the highest activity in the TEAC and LPO assays whereas compounds with protected 5-aminogroup were active in the cellular assay. This is most likely because of their better membrane permeability and intracellular metabolic activation. In summary, we have identified the antioxidant activity of a series of substituted 5-aminopyrimidines and their potential prodrugs which may have implications in the treatment of oxidative stress-related diseases. PMID- 22059897 TI - Nanoparticle attachment on silver corrugated-wire nanoantenna for large increases of surface-enhanced Raman scattering. AB - Using three-dimensional finite-difference time-domain (FDTD) simulation, we described a systematic investigation on the electric field enhancement of the silver corrugated nanowires. The enhancement factor (EF) of surface-enhanced Raman scattering (SERS) for corrugated nanowires can be markedly increased by 1 or 2 orders of magnitude as compared with the smooth nanowires. Moreover, the EF can be further increased with nanoparticle attachment on the corrugated Ag nanowires owing to the coupling between the discrete plasmon state of the nanoparticles and continuum plasmon states of the corrugated nanowire or the crossed corrugated nanowires. The surface plasmonic field distribution of Ag nanowires can be effectively controlled by the polarization of the incident light. Raman spectrum measurements show that the relatively dense corrugated nanowires exhibit a relatively high reproducibility and SERS enhancement attributed to the elimination of polarization-dependent SERS-anisotropic enhancement via the overlapping of randomly distributed Ag nanowires. Such nanostructures as potential nanoantennas offer a route to optimize plasmon coupling for designing miniaturization integration. PMID- 22059898 TI - Common variable immunodeficiency complicated with hemolytic uremic syndrome. AB - Common variable immunodeficiency is a primary immunodeficiency disease characterized by reduced serum immunoglobulins and heterogeneous clinical features. Recurrent pyogenic infections of upper and lower respiratory tracts are the main clinical manifestations of common variable immunodeficiency. Hemolytic uremic syndrome is a multisystemic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia due to platelet aggregation in the arterial microvasculature. This is one of the rare cases of patients diagnosed with common variable immunodeficiency, which was complicated by hemolytic uremic syndrome. PMID- 22059899 TI - Cranial repair: how complicated is filling a "hole"? AB - In general, cranioplasty is viewed as a straightforward surgical procedure, and for many years the complications associated with the procedure have been underestimated. We reviewed our 5-year experience consisting of 218 cranioplasties. Study outcomes focused specifically on the occurrence of complications after cranioplasty. Autologous bone-assisted and prosthetic cranioplasties were considered. Variables described by other authors to be associated with complications were studied, including history of previous cranioplasty, wider craniectomy size, bifrontal craniectomy, and delayed cranioplasty. We also analyzed the influence of material used for craniectomy on the occurrence of complications. The overall complication rate was 19.7%. Nineteen cases of infection (8.7%), 5 cases of postoperative wound dehiscence (2.3%), 6 cases of epidural hemorrhage (2.8%), and 13 cases of cranioplasty dislocation (5.9%) were observed. Bifrontal cranioplasties were more frequently associated with complications (p=0.01; Fisher's exact test) and infection (p<0.0001; Fisher's exact test). Postoperative wound dehiscence was more frequently observed with hand-made or custom-made cranioplasties compared with autologous cranioplasties (p=0.02). Early cranioplasty (<3 months from craniectomy) was significantly associated with cranioplasty dislocation (p=0.03). Logistical regression analysis showed that the only factor independently associated with complication was the site of cranioplasty (p=0.01). In particular, patients with a bifrontal cranioplasty had a 2-fold increased risk of complication (CI 95 1.1-3.6, p=0.017) and a 2.5-fold increased risk of developing infection (CI 95 1.3-4.9, p=0.009) compared with hemispheric/bihemispheric cranioplasty. Our analysis confirms that cranioplasty is burdened by a significant complication rate. In this context, bifrontal cranioplasty is related to a higher risk of complication and, in particular, infection. PMID- 22059900 TI - Curvature and the visual perception of shape: theory on information along object boundaries and the minima rule revisited. AB - Previous empirical studies have shown that information along visual contours is known to be concentrated in regions of high magnitude of curvature, and, for closed contours, segments of negative curvature (i.e., concave segments) carry greater perceptual relevance than corresponding regions of positive curvature (i.e., convex segments). Lately, Feldman and Singh (2005, Psychological Review, 112, 243-252) proposed a mathematical derivation to yield information content as a function of curvature along a contour. Here, we highlight several fundamental errors in their derivation and in its associated implementation, which are problematic in both mathematical and psychological senses. Instead, we propose an alternative mathematical formulation for information measure of contour curvature that addresses these issues. Additionally, unlike in previous work, we extend this approach to 3-dimensional (3D) shape by providing a formal measure of information content for surface curvature and outline a modified version of the minima rule relating to part segmentation using curvature in 3D shape. PMID- 22059901 TI - A stochastic detection and retrieval model for the study of metacognition. AB - We present a signal detection-like model termed the stochastic detection and retrieval model (SDRM) for use in studying metacognition. Focusing on paradigms that relate retrieval (e.g., recall or recognition) and confidence judgments, the SDRM measures (1) variance in the retrieval process, (2) variance in the confidence process, (3) the extent to which different sources of information underlie each response, (4) simple bias (i.e., increasing or decreasing confidence criteria across conditions), and (5) metacognitive bias (i.e., contraction or expansion of the confidence criteria across conditions). In the metacognition literature, gamma correlations have been used to measure the accuracy of confidence judgments. However, gamma cannot distinguish between the first 3 attributes, and it cannot measure either form of bias. In contrast, the SDRM can distinguish among the attributes, and it can measure both forms of bias. In this way, the SDRM can be used to test competing process theories by determining the attribute that best accounts for a change across conditions. To demonstrate the SDRM's usefulness, we investigated judgments of learning (JOLs) followed by cued-recall. Through a series of nested and non-nested model comparisons applied to a new experiment, the SDRM determined that a reduction in variance during the confidence process is the most likely explanation of the delayed-JOL effect, and a stronger relation between information underlying JOLs and recall is the most likely explanation of the testing-JOL effect. Following a brief discussion of implications for JOL theories, we conclude with a broader discussion of how the SDRM can benefit metacognition research. PMID- 22059902 TI - Robotic surgery claims on United States hospital websites. AB - To examine the prevalence and content of robotic surgery information presented on websites of U.S. hospitals. We completed a systematic analysis of 400 randomly selected U.S. hospital websites in June of 2010. Data were collected on the presence and location of robotic surgery information on a hospital's website; use of images or text provided by the manufacturer; use of direct link to manufacturer website; statements of clinical superiority; statements of improved cancer outcome; mention of a comparison group for a statement; citation of supporting data and mention of specific risks. Forty-one percent of hospital websites described robotic surgery. Among these, 37% percent presented robotic surgery on their homepage, 73% used manufacturer-provided stock images or text, and 33% linked to a manufacturer website. Statements of clinical superiority were made on 86% of websites, with 32% describing improved cancer control, and 2% described a reference group. No hospital website mentioned risks. Materials provided by hospitals regarding the surgical robot overestimate benefits, largely ignore risks and are strongly influenced by the manufacturer. PMID- 22059903 TI - Parametric analysis of a novel semi-circular microfluidic CD-ELISA valve. AB - CD-ELISA uses the microfluidic ranking method and centrifugal force to control the testing solution as it flows into the reaction region. The most challenging part of CD-ELISA is controlling the flow process for different biological testing solutions, i.e. the controlling sequence for the microfluidic channel valves. The microfluidic channel valve is therefore the most important fluid channel structure for CD-ELISA. In this study, we propose a valve design suitable for a wide range rotational speeds which can be applied for mass production (molding). Together with supporting experiments, simulation based on two-phase flow theory is used in this study, and the feasibility of this novel valve design is confirmed. Influencing design factors for the microfluidic channel valves in CD ELISA are investigated, including various shapes of the arc, distance d, radius r, the location of the center of the circle, and the contact angle. From both the experimental results and the simulated results, it is evident that the narrowest channel width and the contact angle are the primary factors influencing valve burst frequency. These can be used as the main controlling factors during the design. PMID- 22059904 TI - Functional and anatomic response of the retina and the choroid to intravitreal bevacizumab for macular edema. AB - PURPOSE: This study evaluated the rate of change of best corrected visual acuity (BCVA), central retinal sensitivity, and retinal and choroidal thickness in patients with macular edema after intravitreal bevacizumab. METHODS: This was a prospective, nonrandomized, interventional study. Thirty-four consecutive eyes (34 patients) with macular edema were included in the study. Choroidal neovascularization was present in 21 cases, stage 1 retinal angiomatous proliferation in 6 cases, branch retinal vein occlusion in 4 cases, and diabetic edema in 3 cases. Evaluation of BCVA (Early Treatment Diabetic Retinopathy Study [ETDRS] logarithm of the minimum angle of resolution [LogMAR]), central retinochoroidal thickness (RCT) at standardized A-scan, combined optical coherence tomography/microperimetric assessment of central retinal thickness (RT), central scotoma, and fixation behavior was performed during 12 months after treatment. Choroidal thickness was considered as the difference between RCT and RT. All patients received two initial intravitreal bevacizumab injections (1.25 mg/0.05 mL) at a 1-month interval. RESULTS: BCVA and RT during follow-up were significantly better than at baseline. BCVA was improved of 0.32+/-0.3 LogMAR (P<0.001) at month 1, 0.18+/-0.4 LogMAR (P=0.05) at month 6, and 0.14+/-0.2 (P=0.09) at month 12. RT was reduced by 172.9+/-192.8 MUm (P<0.001) at month 1, 157.7+/-134.2 MUm (P=0.003) at month 6, and 164.3+/-122.3 (P=0.002) at month 12. Mean retinal sensitivity significantly increased during the first month; it decreased afterward, but an improvement if compared with baseline was present at each visit during follow-up. In 23.5% of cases, a choroidal thinning was present during follow-up, and in this group visual acuity at baseline and final visual improvement were significantly greater if compared with patients showing a choroidal thickening. CONCLUSION: Intravitreal bevacizumab for macular edema determines significant functional and anatomic improvement at the 12-month follow up. Visual acuity at baseline and following treatment could be influenced by the choroidal involvement. PMID- 22059905 TI - Current development of the second generation of mTOR inhibitors as anticancer agents. AB - The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, acts as a "master switch" for cellular anabolic and catabolic processes, regulating the rate of cell growth and proliferation. Dysregulation of the mTOR signaling pathway occurs frequently in a variety of human tumors, and thus, mTOR has emerged as an important target for the design of anticancer agents. mTOR is found in two distinct multiprotein complexes within cells, mTORC1 and mTORC2. These two complexes consist of unique mTOR-interacting proteins and are regulated by different mechanisms. Enormous advances have been made in the development of drugs known as mTOR inhibitors. Rapamycin, the first defined inhibitor of mTOR, showed effectiveness as an anticancer agent in various preclinical models. Rapamycin analogues (rapalogs) with better pharmacologic properties have been developed. However, the clinical success of rapalogs has been limited to a few types of cancer. The discovery that mTORC2 directly phosphorylates Akt, an important survival kinase, adds new insight into the role of mTORC2 in cancer. This novel finding prompted efforts to develop the second generation of mTOR inhibitors that are able to target both mTORC1 and mTORC2. Here, we review the recent advances in the mTOR field and focus specifically on the current development of the second generation of mTOR inhibitors as anticancer agents. PMID- 22059906 TI - Recent progress in the study of methylated tumor suppressor genes in gastric cancer. AB - Gastric cancer is one of the most common malignancies and a leading cause of cancer mortality worldwide. The pathogenesis mechanisms of gastric cancer are still not fully clear. Inactivation of tumor suppressor genes and activation of oncogenes caused by genetic and epigenetic alterations are known to play significant roles in carcinogenesis. Accumulating evidence has shown that epigenetic silencing of the tumor suppressor genes, particularly caused by hypermethylation of CpG islands in promoters, is critical to carcinogenesis and metastasis. Here, we review the recent progress in the study of methylations of tumor suppressor genes involved in the pathogenesis of gastric cancer. We also briefly describe the mechanisms that induce tumor suppressor gene methylation and the status of translating these molecular mechanisms into clinical applications. PMID- 22059907 TI - Epigenetic changes in colorectal cancer. AB - Epigenetic changes frequently occur in human colorectal cancer. Genomic global hypomethylation, gene promoter region hypermethylation, histone modifications, and alteration of miRNA patterns are major epigenetic changes in colorectal cancer. Loss of imprinting(LOI) is associated with colorectal neoplasia. Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation. HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment. Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer. This review is mainly focused on DNA methylation, histone modification, and microRNA changes in colorectal cancer. PMID- 22059908 TI - Aberrant promoter CpG methylation and its translational applications in breast cancer. AB - Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations. Recent studies revealed that abnormal gene expression induced by epigenetic changes, including aberrant promoter methylation and histone modification, plays a critical role in human breast carcinogenesis. Silencing of tumor suppressor genes (TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression, thus directly contributing to breast tumorigenesis. Usually, aberrant promoter methylation of TSGs, which can be reversed by pharmacological reagents, occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer. In this review, we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer. PMID- 22059909 TI - Local recurrence of a parosteal osteosarcoma 21 years after incomplete resection. AB - Parosteal osteosarcoma (POS) is the most common form of surface osteosarcoma. Its symptoms are insidious and its duration prior to diagnosis is considerably longer than that of other types of osteosarcoma. We report a case of POS with a growing mass but no evidence of metastasis. This tumor, which was diagnosed as calcified hematoma with benign characteristics, was incompletely resected in our hospital 21 years before the diagnosis of recurrence. The patient underwent a wide en bloc resection in our hospital and was free of symptoms, with no signs of tumor recurrence or metastasis during a 53-month follow-up. PMID- 22059910 TI - The evolution of phase I trials in cancer medicine: a critical review of the last decade. AB - The advent of targeted therapies, combined with an unsustainable rate of failure in oncology drug development, has resulted in a number of new approaches to clinical trials. Early clinical trials are no exception, with efforts to improve the eventual success rate of late stage trials through evolving phase I trial methodologies, the addition of extensive pharmacodynamic studies, and early adoption of patient selection strategies. Unfortunately, some of these new approaches have met with mixed results. Furthermore, no clear metrics are available to determine whether these designs are more successful than previous strategies. This review examines the evolution of phase I trials and draws upon several examples of strategies that have been successful as well as those that have not, and outlines a pragmatic approach to phase I trials as our understanding of the molecular biology of individual malignancies emerges. PMID- 22059911 TI - Potential of vesicular stomatitis virus as an oncolytic therapy for recurrent and drug-resistant ovarian cancer. AB - In the last decade, we have gained significant understanding of the mechanism by which vesicular stomatitis virus (VSV) specifically kills cancer cells. Dysregulation of translation and defective innate immunity are both thought to contribute to VSV oncolysis. Safety and efficacy are important objectives to consider in evaluating VSV as a therapy for malignant disease. Ongoing efforts may enable VSV virotherapy to be considered in the near future to treat drug resistant ovarian cancer when other options have been exhausted. In this article, we review the development of VSV as a potential therapeutic approach for recurrent or drug-resistant ovarian cancer. PMID- 22059912 TI - Anti-tumor effect of oncolytic herpes simplex virus G47delta on human nasopharyngeal carcinoma. AB - Oncolytic herpes simplex virus (HSV) can replicate in and kill cancer cells without harming normal tissue. G47delta is a third-generation HSV vector. In this study, the therapeutic effects of G47delta on human nasopharyngeal carcinoma (NPC) were determined in vitro and in vivo. The human NPC cell lines CNE-2 and SUNE-1, primary normal nasopharyngeal epithelial cells (NPECs), and immortalized nasopharyngeal cells NP-69 and NPEC2/Bmi1 were infected with G47delta at different multiplicities of infection (MOIs). The survival of infected cells was observed daily. Two subcutaneous models of NPC were established with CNE-2 and SUNE-1 in Balb/c nude mice. G47delta or virus buffer as control was injected into the subcutaneous tumors. Tumor size was measured twice a week, and animals were euthanized when the diameter of their tumors exceeded 18 mm or when the animals appeared moribund. For the NPC cell lines CNE-2 and SUNE-1, more than 85% and 95% of cells were killed on day 5 after G47delta infection at MOI = 0.01 and MOI = 0.1, respectively. Similar results were observed for an immortalized cell line NPEC2/Bmi-1. A moderate effect of G47delta was also found on another immortalized cell line NP-69, of which only 27.7% and 75.9% of cells were killed at MOI = 0.01 and MOI = 0.1, respectively. On the contrary, there was almost no effect observed on NPECs. The in vivo experiments showed that tumors in mice in the G47delta treated group regressed completely, and the mice exhibited much longer survival time than those in the control groups. Our results suggest that the potential therapeutic effects of G47delta would be applicable for treatment of NPC patients in the future. PMID- 22059914 TI - Relationship of physically separable lean with chemical lean in pig carcasses. AB - This study was conducted to examine the relationships between 'physically separable lean' (carried out by the Kulmbach reference technique) and 'lean' determined by moisture or lipid analysis (called chemical lean). Five major cuts (ham, shoulder, loin, belly and neck), originating from the Hungarian cross-breed 'Hungahyb', were dissected and the weights recorded. The moisture and lipid contents of three tissue groups (lean, intermuscular fatty tissue and remainder) were determined by common laboratory methods. Adequate estimators (predictors) were then developed for the assessment of standardized or non-standardized lean content in the 'boneless cut' (without skin and subcutaneous fatty tissue). It was shown that the concept of moisture-standardized lean is analogous to that of the fat-standardized one. It appears that unbiased estimators could be obtained if the interdependences between the chemical composition (moisture or lipid content) of the lean, the 'residue' (intermuscular fatty tissue + remainder) and that of the 'boneless cut' are included in the respective equations. If these interdependences are neglected and only the corresponding means are used in these equations, biased estimates have been obtained for the standardized or non standardized lean content in the 'boneless cut'. Difficulties arising at practical application of these concepts are also discussed in this paper. PMID- 22059915 TI - The estimation of beef carcass muscle using cross-sectional area of M. longissimus dorsi at the fifth rib. AB - The improvements in the accuracy of prediction of side muscle (weight and proportion) using measurements of eye muscle area at the 10th rib (EMA(10)) and eye muscle area at the 5th rib (EMA(5)), were compared in 48 steers, grain-fed for the Japanese market. For side muscle proportion the addition of EMA(10) to hot side weight and a fat thickness measurement did not improve prediction but the addition of EMA(5) did. P8 fat thickness together with hot side weight and EMA(5) (each, P<0.001) predicted side muscle proportion with an SEE of 2.05% and an R(2) of 61%, while the values for 10th rib thickness together with hot side weight and EMA(5) (each, P<0.001) were 2.09% and 68%, respectively. For the prediction of side muscle weight a fat thickness measurement and hot side weight (both, P<0.001) explained 77-84% of variance; the addition of an eye muscle area measurement further improved prediction with the most accurate being P8 fat thickness together with hot side weight and EMA(5). PMID- 22059916 TI - Sex and crossbreed effects on the characteristics of dry-cured ham. AB - The right ham of 76 gilts and 82 barrows from five different crossbreeds, which included Duroc (DU), Landrace (LR), Large White (LW) and Belgian Landrace (BL) lines - DUx(LRxLW), LWx(DUxLW), LWx(LRxLW), BLx(DUxLW) and BLx(LRxLW) - were processed to produce dry cured hams. The external appearance of the hams, and the colour and thickness of the subcutaneous fat were determined. Chemical analyses, appearance, texture, flavour and odour were evaluated on biceps femoris (BF) muscle. The hams from the barrows showed a thicker and whiter layer of subcutaneous fat, higher marbling and lower processing loss than those from gilts. Hams from DU-sired pigs presented the highest marbling, but the worst texture characteristics. The texture characteristics of the hams from the LBx(LRxLW) cross were similar to those of the hams from DU-sired pigs. The hams from the LW-sired crosses showed the highest intensity of holes surrounding the coxo-femoral joint. The LBx(DUxLW) could be the most suitable among the five crosses studied for dry-cured ham production under the processing conditions used in this study. PMID- 22059917 TI - Atmosphere and blooming time affect color and lipid stability of frozen beef from steers supplemented with Vitamin E. AB - The influence of blooming time (1, 6 or 48 h) and atmosphere (air or 100% oxygen) on color and lipid stability of frozen Longissimus lumborum (LL) from control and vitamin E supplemented steers was studied. Samples were stored at -20 degrees C with or without illumination. Blooming control LL for 48 h in air followed by dark storage increased discoloration. Supplementation and blooming in oxygen, separately or combined, increased color display life. Illumination increased discoloration. Supplementation coupled with blooming for 6 or 48 h in 100% oxygen provided the highest color stability in both dark and illuminated storage. Color display lives for supplemented LL bloomed for 6 and 48 h in oxygen were 182 and 212 days for dark storage, and 21 and 73 days for illuminated display. Supplementation decreased lipid oxidation in illuminated LL, but blooming for 48 h in oxygen minimized this effect. PMID- 22059918 TI - Partial replacement of sodium chloride with potassium chloride in dry fermented sausages: Influence on carbohydrate fermentation and the nitrosation process. AB - Two types of dry fermented sausages were manufactured: type A with traditional formulation and type B with reduced sodium content. pH and a(w) values and the counts of aerobic mesophiles, Enterobacteriaceae and lactobacilli micro-organisms during the ripening of both fermented sausages were similar. Final lactic acid contents were also similar, but carbohydrate content was significantly lower in type B sausage. Content of acetic, propionic and butyric acids were significantly higher in type B, suggesting a higher heterofermentative activity. Also type B sausage showed lower nitrate level and higher chemical conversion percentage, suggesting a higher nitrosation intensity. PMID- 22059919 TI - Dry fermented sausages elaborated with lipase from Candida cylindracea. Comparison with traditional formulations. AB - The addition of microbial lipase to fermented sausages was studied. A sausage with lipase from Candida cylindracea and a control sausage with starter (Lactobacillus plantarum and Staphylococcus carnosus) were produced in a pilot plant. The acidity value and the amounts of the different free fatty acids (FFA) showed a higher intensity of lipolytic activity in sausages with lipase than in sausages with starter. In sausages with lipase, the percentage of saturated FFA was greater and that of polyunsaturated FFA was lower than in sausage with starter. Mono-unsaturated FFA percentage was similar in both sausages. TBA and peroxide values indicated that the increase of FFA produced by lipase action did not increase the rancidity. A slight increase in acetic, propionic and butyric acids was observed in sausage with lipase but this was not sufficient to develop excessive acidity in the product. PMID- 22059920 TI - The measurement of meat pigments by fibre-optic reflectance spectrophotometry using the Kubelka-Munk equation. AB - A reflectance spectrophotometry system with an adhesive pad type fibreoptic probe was developed to measure a wide range of absorbance. The performance of the instrument was evaluated by undertaking in vitro measurements of the reflectance spectra of metmyoglobin solution and meat pastes containing known amounts of oxy , deoxy- and metmyoglobin. The absorbance of metmyoglobin solution in the range of 0-4 mg/dl as successfully distinguised, but at the upper range of 4 mg/ml the reflectance results were not in proportion to the concentration. All absorbances at 525 nm for meat pastes were also not in proportion to the concentration. These non-linearities were considered to be a result of back-scattering. Therefore, the K/S value of the Kubelka-Munk equation was applied in an effort the refine the fibre optic reflectance method. Positive correlations between the myoglobin concentration and the K/S values obtained from spectra of meat pastes were found. PMID- 22059921 TI - The influence of controlled atmosphere and vacuum packaging upon chilled pork keeping quality. AB - A total of 48 pork loin section (1 kg) with normal inherent muscle quality were utilized to evaluate and compare the effects of a vacuum packaging system and a CO(2) controlled atmosphere packaging system on keeping quality of chilled pork stored at -1.5 degrees C. Results indicated based upon appearance CO(2) packaged porl loin had a storage life of greated than 15 weeks and vacuum packaged pork loid had a storage life of slightly over 12 weeks. However, off-flavor development coinciding with lactic acid bacteria reaching maximum numbers presently restricts the actual storage life of pork loin stored at -1.5 degrees C to 9 weeks in both packaging treatments. Therefore, if microbial contamination on the commercial product can be reduced significantly to prevent spoilage organisms, including lactics, from rapidly growing to maximum numbers, storage life of pork loin at -1.5 degrees C can be extended sufficiently to accomodate all domestic and export applications using either vacuum or CO(2) packaging. PMID- 22059922 TI - Lipid and cholesterol oxidation in Chinese-style sausage using vacuum and modified atmosphere packaging. AB - The oxidation of lipid and cholesterol in Chinese-style sausage in vacuum packaging (VP) and modified atmosphere packaging (MAP) stored at 4 degrees C and 15 degrees C, respectively, for 5 months was investigated. The 2-thiobarbitaric acid reactive substance (TBARS) and peroxide value (POV) of sausage were variable with packaging treatments during storage. TBARS and POV in sausage stored at 15 degrees C were significantly greater (p < 0.05) than at 4 degrees C, and the MAP treatment was more stable than the VP treatment. In addition, the polyunsaturated fatty acids (PUFA) in sausage decreased with storage for both treatments. The content of cholesterol decreased significantly after 3 months of storage. 7-beta hydroxycholesterol, 7-ketocholesterol and 22-ketocholesterol were the major cholesterol oxidation products (COPs), but there was no detectable (< 1 MUg/100 g) 25-hydroxycholesterol or cholestanetriol with either treatment. PMID- 22059923 TI - Quality of beef from commercial fattening systems in Northern Germany. AB - The objectives of this study were to gather information on the quality of beef carcasses representative of commercial fattening systems and a new fattening regime for intensively fattened heifers. Data on the classification of the carcasses into the EC beef categories were analysed. In all 48 carcasses from the following categories were analysed: 10 intensively fattened heifers, eight young bulls, eight steers, eight heifers, eight dairy cows, and six once-bred heifers. Various approaches of univariate and multivariate analysis were conducted to analyse beef quality of M. longissimus dorsi and M. semitendinosus. The analysis reveals that variation of beef quality assessments is great within and between categories. A significant interaction between category and cooking condition was recorded for M. longissimus dorsi tenderness. As opposed to beef of intensively fattened heifers the sample of dairy cows is darkest with the lowest soluble collagen and the highest shear values. Assessments of the remaining categories are between these categories. The difference between intensively fattened heifers and dairy cows of shear work done was 0.218 J, of lightness (L) was 8.6 and of solubility of collagen was 11.8%. Meat prepared at low temperature is much more tender (shear work done was 11% lower) and had just 30% cooking loss compared to beef of samples prepared at internal temperatures above 70 degrees C. Clustering based segmentation provides a lower variation of beef quality within clusters than the variation of beef quality within EC categories. PMID- 22059924 TI - Muscle glycogen level and meat quality in pigs of different halothane genotypes. AB - The halothane genotype of 22 Polish landrace pigs was determined using halothane test and blood typing. Eight homozygous normal (NN), eight hetero-zygotes (Nn) and six homozygous recessive (nn) were identified. The levels of glycogen and lactate were measured in biopsy samples taken from the longissimus lumborum using a shot biopsy technique. pH (pH(1)) and IMP/ATP ratio (R) were determined at 30 min after slaughter, while pH, meat colour and water holding capacity were determined on the day after slaughter. The halothane genotype did not affect intra vitam glycogen level. The nn pigs had a higher R value and lower pH(1) than both Nn and NN animals. Heterozygous animals were intermediate between both homo zygotes for biopsy lactate level and meat colour. The lactate content of biopsy samples was significantly correlated with pH(1) (r = -0.68; P < 0.01), R (r = 0.68; P < 0.01), meat colour (r = 0.57; P < 0.01) and water holding capacity (r = 0.45; P . 0.05). PMID- 22059925 TI - Dipyrrolylmethane-based macrobicyclic azacryptand: synthesis, X-ray structures, conformational and anion binding properties. AB - A new class of macrobicyclic azacryptand containing dipyrrolylmethane subunits with nitrogen bridgeheads was synthesized by the Mannich reaction of the dipyrrolylmethane in the presence of aqueous ammonia. The azacryptand exhibits a staggered conformation in the solid state, but is in a dynamic equilibrium with the eclipsed conformation in solution studied by the variable-temperature (1)H NMR methods. The azacryptand has a specific size suitable only for fluoride ion; large anions such as NO(3)(-) bind in the clefts of the macrobicycle as shown by the X-ray structures of its fluoride ion inclusion and the nitrate anion complexes. The anion binding studies showed that it has high selectivity and affinity for fluoride ion in acetone over other anions studied, which was supported by (1)H and (19)F NMR methods. The azacryptand has fast fluoride ion mediated proton-deuterium exchanges with acetone-d(6) studied by the (19)F NMR method. PMID- 22059926 TI - Surgical treatment of primitive gastro-intestinal lymphomas: a systematic review. AB - Primitive Gastrointestinal Lymphomas (PGIL) are uncommon tumours, although time trend analyses have demonstrated an increase. The role of surgery in the management of lymphoproliferative diseases has changed over the past 40 years. Nowadays their management is centred on systemic treatments as chemo /radiotherapy. Surgery is restricted to very selected indications, always discussed in a multidisciplinary setting. The aim of this systematic review is to evaluate the actual role of surgery in the treatment of PGIL. A systematic review of literature was conducted according to the recommendations of The Cochrane Collaboration. Main outcomes analysed were overall survival (OS) and disease free survival (DFS). There are currently 1 RCT and 4 non-randomised prospective controlled studies comparing surgical versus medical treatment for PGIL. Seven hundred and one patients were analysed, divided into two groups: 318 who underwent to surgery alone or associated with chemotherapy and/or radiotherapy (surgical group) versus 383 who were treated with chemotherapy and/or radiotherapy (medical group). Despite the OS at 10 years between surgical and medical groups did not show relevant differences, the DFS was significantly better in the medical group (P=0.00001). Accordingly a trend was noticed in the recurrence rate, which was lower in the medical group (6.06 vs. 8.57%); and an higher mortality was revealed in the surgical group (4.51% vs. 1.50%).The chemotherapy confirms its primary role in the management of PGIL as part of systemic treatment in the medical group. Surgery remains the treatment of choice in case of PGIL acutely complicated, although there is no evidence in literature regarding the utility of preventive surgery. PMID- 22059927 TI - Enzymatically degradable mussel-inspired adhesive hydrogel. AB - Mussel-inspired adhesive hydrogels represent innovative candidate medical sealants or glues. In the present work, we describe an enzyme-degradable mussel inspired adhesive hydrogel formulation, achieved by incorporating minimal elastase substrate peptide Ala-Ala into the branched poly(ethylene glycol) (PEG) macromonomer structure. The system takes advantage of neutrophil elastase expression upregulation and secretion from neutrophils upon recruitment to wounded or inflamed tissue. By integrating adhesive degradation behaviors that respond to cellular cues, we expand the functional range of our mussel-inspired adhesive hydrogel platforms. Rapid (<1 min) and simultaneous gelation and adhesion of the proteolytically active, catechol-terminated precursor macromonomer was achieved by addition of sodium periodate oxidant. Rheological analysis and equilibrium swelling studies demonstrated that the hydrogel is appropriate for soft tissue-contacting applications. Notably, hydrogel storage modulus (G') achieved values on the order of 10 kPa, and strain at failure exceeded 200% strain. Lap shear testing confirmed the material's adhesive behavior (shear strength: 30.4 +/- 3.39 kPa). Although adhesive hydrogel degradation was not observed during short-term (27 h) in vitro treatment with neutrophil elastase, in vivo degradation proceeded over several months following dorsal subcutaneous implantation in mice. This work represents the first example of an enzymatically degradable mussel-inspired adhesive and expands the potential biomedical applications of this family of materials. PMID- 22059928 TI - Production of porous silica microparticles by membrane emulsification. AB - A method for the production of near-monodispersed spherical silica particles with controllable porosity based on the formation of uniform emulsion droplets using membrane emulsification is described. A hydrophobic metal membrane with a 15 MUm pore size and 200 MUm pore spacing was used to produce near-monodispersed droplets, with a mean size that could be controlled between 65 and 240 MUm containing acidified sodium silicate solution (with 4 and 6 wt % SiO(2)) in kerosene. After drying and shrinking, the final silica particles had a mean size in the range between 30 and 70 MUm. The coefficient of variation for both the droplets and the particles did not exceed 35%. The most uniform particles had a mean diameter of 40 MUm and coefficient of variation of 17%. By altering the pH of the sodium silicate solution and aging the gel particles in water or acetone, the internal structure of the silica particles was successfully modified, and both micro- and mesoporous near-monodispersed spherical particles were produced with an average internal pore size between 1 and 6 nm and an average surface area between 360 and 750 m(2) g(-1). A material balance and particle size analysis provided identical values for the internal voidage of the particles, when compared to the voidage as determined by BET analysis. PMID- 22059929 TI - Altering the electrostatic potential in the major groove: thermodynamic and structural characterization of 7-deaza-2'-deoxyadenosine:dT base pairing in DNA. AB - As part of an ongoing effort to explore the effect of major groove electrostatics on the thermodynamic stability and structure of DNA, a 7-deaza-2' deoxyadenosine:dT (7-deaza-dA:dT) base pair in the Dickerson-Drew dodecamer (DDD) was studied. The removal of the electronegative N7 atom on dA and the replacement with an electropositive C-H in the major groove was expected to have a significant effect on major groove electrostatics. The structure of the 7-deaza dA:dT base pair was determined at 1.1 A resolution in the presence of Mg(2+). The 7-deaza-dA, which is isosteric for dA, had minimal effect on the base pairing geometry and the conformation of the DDD in the crystalline state. There was no major groove cation association with the 7-deaza-dA heterocycle. In solution, circular dichroism showed a positive Cotton effect centered at 280 nm and a negative Cotton effect centered at 250 nm that were characteristic of a right handed helix in the B-conformation. However, temperature-dependent NMR studies showed increased exchange between the thymine N3 imino proton of the 7-deaza dA:dT base pair and water, suggesting reduced stacking interactions and an increased rate of base pair opening. This correlated with the observed thermodynamic destabilization of the 7-deaza-dA modified duplex relative to the DDD. A combination of UV melting and differential scanning calorimetry experiments were conducted to evaluate the relative contributions of enthalpy and entropy in the thermodynamic destabilization of the DDD. The most significant contribution arose from an unfavorable enthalpy term, which probably results from less favorable stacking interactions in the modified duplex, which was accompanied by a significant reduction in the release of water and cations from the 7-deaza-dA modified DNA. PMID- 22059930 TI - Expression of matrix metalloproteinases, type IV collagen, and interleukin-10 in rabbits treated with morphine after lamellar keratectomy. AB - PURPOSE: To study the effects of topical administration of 1% morphine on corneal analgesia in rabbits submitted to lamellar keratectomy and to assess the expression of matrix metalloproteinase-1, metalloproteinase-2, metalloproteinase 9 (MMPs), type IV collagen, and interleukin-10 (IL-10) during the treatment. METHODS: Morphine group (MG) received 50 MUL of topical 1% morphine four times daily, while the control group received saline instead. Corneal touch threshold (CTT) and the wound area were assessed until corneal healing. Corneal samples were processed for routine histology, immunohistochemistry, zymography, and ELISA. RESULTS: Following keratectomy, CTT increased significantly from 6 to 96 h time points. Mean corneal re-epithelization rate and scores of leukocyte infiltration did not differ significantly between treatment groups. Immunolabeling pattern for MMP-1, MMP-9, and type IV collagen was similar in both treatment groups. In the MG, zymography indicated significantly higher levels of active MMP-2 on days 6 and 12; and in the latent MMP-9, on days 3 and 6, and in the active MMP-9, on day 6. Latent MMP-2 and MMP-9, and active MMP-9 decreased to values close to those of healthy corneas on day 12, but levels of active MMP-2 remained significantly elevated in the MG. IL-10 levels measured on days 1-6 were reduced as compared to those of healthy corneal tissue and returned to levels close to those of healthy corneas on day 12. CONCLUSION: Topical morphine promoted corneal analgesia for up to 4 days and did not delay corneal re epithelization. The re-establishment of MMPs and IL-10 to levels close to baseline values at the end of the study and the expression of type IV collagen in both groups reinforce that, with caution, 1% morphine can be used after lamellar keratectomy in rabbits. PMID- 22059931 TI - Ligand-promoted C3-selective arylation of pyridines with Pd catalysts: gram-scale synthesis of (+/-)-preclamol. AB - The first example of Pd-catalyzed, C3-selective arylation of unprotected pyridines has been developed by employing a catalytic system consisting of Pd(OAc)(2) and 1,10-phenanthroline. This protocol provides an expeditious route to an important class of 3-arylpyridines and 3-arylpiperidines frequently found in bioactive compounds. A brief synthesis of the drug molecule (+/-)-preclamol is also reported. PMID- 22059932 TI - Treatment with probiotics in experimental oral colonization by Candida albicans in murine model (DBA/2). AB - The aim of this study is to evaluate the oral colonization by Candida albicans in experimental murine immunosuppressed DBA/2 and treatment with probiotic bacteria. To achieve these objectives, 152 DBA/2-immunosuppressed mice were orally inoculated with a suspension of C. albicans containing 10(8) viable yeast cells, the animals were treated with nystatin or with the probiotics (Lactobacillus acidophilus and Lactobacillus rhamnosus). Evaluations were performed by Candida count from oral mucosa swabbing. The oral mucosa colonization by C. albicans started at day 1 after inoculation, remained maximal from day 3 until day 7, and then decreased significantly. Probiotics reduced the C. albicans colonization significantly on the oral mucosa in comparison with the untreated animal group. In the group treated with L. rhamnosus, the reduction in yeast colonization was significantly higher compared with that of the group receiving nystatin. Immunosuppressed animal model DBA/2 is a relevant model for experimental Candida oral colonization, and the treatment with probiotics in this model may be an effective alternative to prevent it. PMID- 22059933 TI - A preliminary randomized controlled study to determine the application frequency of a new lymphoedema bandaging system. AB - BACKGROUND: Bandaging plays an important role in the treatment of lymphoedema. OBJECTIVE: To investigate efficacy and safety of the 3MTM CobanTM 2 compression system (Coban 2 system) with different application frequencies in comparison to short-stretch bandaging. METHODS: A multicentre, randomized, prospective study was performed with 82 patients suffering from arm or leg lymphoedema stage II or late stage II. Patients were allocated to traditional short-stretch bandaging five times per week or to the Coban 2 system applied two, three or five times per week for 19 days. Limb volume and adverse events were recorded at each study visit. The primary endpoint was percentage volume reduction. RESULTS: The highest lymphoedema volume reduction was achieved with the Coban 2 system applied two times per week. A mean reduction of 18.7% (SD 14.5) in legs and 10.5% (SD 8.3) in arms was achieved. More frequent bandage changes of three and five times per week did not demonstrate additional benefits. Short-stretch bandaging five times per week showed a mean volume reduction of 10.9% (SD 5.2) and 8.2% (SD 3.1) for legs and arms, respectively. Bandage slippage was low for all treatment groups. A relevant change in overall mobility was achieved during the use of the Coban 2 system. The adverse reactions were in agreement with already known side-effects and did not differ remarkably between the treatment groups. CONCLUSION: The 3MTM CobanTM 2 compression system applied twice weekly demonstrated a high rate of volume reduction and a good safety profile. Oedema reduction was still effective with 4 days between bandage change, which allows a constant therapeutic effect in routine practice. This should give the patient a high degree of independence and mobility. PMID- 22059935 TI - A pilot genome wide association and gene expression array study of suicide with and without major depression. AB - OBJECTIVES: Suicide is partly heritable but the responsible genes have not been identified. We conducted a gene-centric, low coverage single nucleotide polymorphism (SNP) pilot genome-wide association study (GWAS) seeking new candidate regions in suicides with and without depression, combined with gene expression assay of brain tissue. METHODS: Ninety-nine Caucasian subjects, including 68 who completed suicide and 31 who died suddenly from other causes, were genotyped postmortem using GeneChip(r) Mapping 50K Xba. Clinical data were obtained from relatives. SNPs with Hardy-Weinberg equilibrium P values below 0.001 were excluded from analysis. Illumina chip expression arrays assayed the transcriptome in prefrontal cortex in a drug-free subgroup. RESULTS: GWAS analysis (cutoff P < 0.001) yielded 58 SNPs, 22 of them in or near 19 known genes, with risk allele-associated odds ratios between 2.7 and 6.9. Diagnosis of mood disorder did not explain the associations. Some of the SNPs matched into four functional groups in gene ontology. Gene expression in the prefrontal and the anterior cingulate cortex for these 19 genes was measured on a separate, though overlapping, sample of suicides and seven of 19 genes showed altered expression in suicides as compared with controls, especially in immune system related genes. CONCLUSIONS: Matching GWAS findings with expression data assesses functional effect of new candidate genes in suicide, and is an alternative form of confirmation or replication study. Results highlight a role for neuroimmunological effects in suicidal behaviour. PMID- 22059936 TI - An international survey of reported prescribing practice in the treatment of patients with generalised anxiety disorder. AB - OBJECTIVE: To gain insight into the experience and practice of psychiatrists in the pharmacological management of patients with generalized anxiety disorder (GAD). METHODS: Multiple-choice questionnaire completed by 501 psychiatrists (representing a 45% response rate) from 18 countries, selected by pharmaceutical company representatives to attend a scientific meeting, through having an interest in anxiety disorders. RESULTS: Use of screening tools, routine structured diagnostic interviews, and practice guidelines was infrequent. Over one-third of patients did not receive their initial psychiatric consultation within a month after referral. A total of 45% of patients had symptoms for 2 years or longer before being diagnosed and treated. Most patients had been treated with benzodiazepines before referral. 80% of respondents always or often prescribed selective serotonin reuptake inhibitors (SSRIs), 43% serotonin norepinephrine reuptake inhibitors (SNRIs), or pregabalin (35%) as first-line treatments. The most frequently recommended second-line treatments were SNRIs (41%) and pregabalin (36%). Concentration difficulties, fatigue, excessive worrying and pain were reported as the symptoms most difficult to manage. CONCLUSIONS: Patients with GAD have frequently been treated with benzodiazepines before referral to a psychiatrist. SSRIs were the preferred first-line treatment, and SNRIs and pregabalin preferred second-line treatments. Reported practice in this sample appears largely consistent with recent evidence-based treatment guidelines. PMID- 22059937 TI - Treatment with levetiracetam in a patient with pervasive developmental disorders, severe intellectual disability, self-injurious behavior, and seizures: a case report. AB - Pervasive developmental disorder is characterized by various symptoms that often include self-injurious behavior (SIB). Episodes of SIB occur in the context of high emotional arousal, anger, or fear and may be related to epilepsy. We report the case of a 20-year-old man with pervasive developmental disorder presenting with SIB non-responsive to antipsychotic medication. Positron emission tomography showed a right temporoparietal hypometabolic focal lesion suggestive of an epileptic focus. Two weeks after initiation of levetiracetam (Keppra(r)), SIB disappeared, without recurrence 24 months later. Levetiracetam (Keppra(r)) may be beneficial for such patients. PMID- 22059938 TI - Impact of emotional approach coping and hope on PTSD and depression symptoms in a trauma exposed sample of Veterans receiving outpatient VA mental health care services. AB - The present investigation evaluates the relationship between coping style, dispositional hope, and posttraumatic stress disorder (PTSD) and depression symptom severity in a trauma-exposed Veteran sample. Specifically, we evaluated the adaptive value of emotional avoidant and approach coping strategies and perceptions of hope in a sample of 209 trauma-exposed Veterans receiving outpatient mental health care at a VA facility. Participants completed a life events questionnaire and inventories assessing coping, dispositional hope, and PTSD and depression symptom severity. Hierarchical regression analyses were conducted controlling for relevant demographic variables. Greater levels of emotional avoidance and lower levels of emotional expression were significantly associated with increased PTSD and depression symptom severity. Dispositional hope was positively associated with depression symptoms only and perceptions of hope moderated the association between emotional avoidance coping and depression symptoms. Findings highlight the value of emotional coping strategies and perceptions of hope in posttraumatic adjustment. Specifically, employing coping techniques that encourage emotional expression may promote improved adjustment among trauma-exposed individuals, while reduced perceptions of hope and the use of avoidant coping strategies may place individuals at greater risk for depression following exposure to traumatic events. PMID- 22059940 TI - Effect of heating rate on shortening, ultrastructure, and fracture behavior of prerigor beef muscle. AB - Rapidly heated prerigor beef is tender because of incompletely described myofibrillar disruption and tissue fracture. This study was designed to evaluate the effects of heating rate on heat-induced myofibrillar shortening, ultrastructural changes, and fracture behavior in prerigor triceps brachii muscle. Rapid heating (2 degrees C/2 min) to 53 degrees C caused (P < 0.05) more severe myofibrillar shortening in a shorter time and at higher muscle pH and temperature, less muscle weight loss, and shorter sarcomeres than slow heating (2 degrees C/12 min) to 47 or 53 degrees C. Rapid heating caused more extensive degradation of A and I bands, greater loss of the tridimensional pattern of myofibrils, more fragmentation and melting of myofibrils, widened intermyofibrillar spaces, and maximum separation of fiber bundles as compared to slow heating. Slow heating caused extensive shortening but not extensive degradation and disruption of myofibrils. Muscles slowly heated to 53 degrees C sustained greater loss of structural integrity than those slowly heated to 47 degrees C, but fracture behavior was similar. Separation and fracture occurred near the perimysial/endomysial junction in all heated samples, but the perimysium remained affixed to the endomysium at one side of the interface in many rapidly heated samples. Longitudinal fractures showed a granular endomysium and large numbers of supercontraction nodes alternating with areas of sarcolemmal membrane fragmentation and fiber tearing in rapidly heated samples. Alterations of myofibrillar ultrastructure and fiber structure, and separation of bundles, may account for enhanced tenderness of rapidly heated prerigor muscle. PMID- 22059941 TI - Investigation of the levels of free purine and pyrimidine bases and metabolites in mechanically recovered meats. AB - Levels of free purine and pyrimidine bases and metabolites, in particular xanthine, have been investigated in poultry meat and MRM as potential qualitative or quantitative markers for the presence of MRM in meat products. Only xanthine was found to exhibit significantly different levels between the source meat and MRM product where, for example, it was found to be present at approximately 100 MUg/g in turkey MRM but only 57, 33 and 14 MUg/g in the neck, leg and breast meat respectively. The wide variation in levels within a cut, together with the overlap between figures for source meat and MRM, preclude the use of xanthine as a robust qualitative or quantitative marker. Processing of turkey meat by subjecting it to an increasing level of comminution does not appear to elevate the indigenous level of free xanthine. PMID- 22059942 TI - Titin content of beef in relation to tenderness. AB - Steaks obtained from the longissimus dorsi muscle of 24 crossbred steers were subjected to four treatments (unaged raw, aged raw, unaged cooked, aged cooked) and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Titin migrated primarily as a single protein band in unaged raw samples (48 h post mortem), as a doublet in aged (16 days) raw samples, and as a triplet in unaged and aged cooked samples. Total titin band density remained constant among steaks that varied widely in Warner-Bratzler shear value, suggesting that beef steaks varying in tenderness contain the same amount of titin. It is concluded that titin content, as determined by gel electrophoresis, does not distinguish 'tough' from 'tender' beef. PMID- 22059943 TI - The effect of bruised beef addition on the quality of processed meat products. AB - The aim of this study was to determine the levels of bruised beef that could be incorporated into processed meat products without detrimental effects on product quality. Bruised beef was incorporated into fresh sausages, Devon and semi-dry salami, and compared to products containing unbruised beef. Up to 30%, 25% and 65% of the unbruised beef in fresh sausages, Devon and semidry salami respectively can be replaced with bruised beef with no detrimental effect on product quality (as assessed by a sensory panel), either initially or over the shelf-life of the product at 4 degrees C. The level of bruised beef which can be incorporated into meat products is predominantly limited by its effect on product colour. The microbiological and compositional qualities of meat products containing bruised beef are similar to those containing unbruised beef. PMID- 22059944 TI - Heat-induced gelation of actomyosin. AB - Rheological properties of actomyosin gels were markedly affected by protein concentration, pH and heating temperature. Gel strength increased with increasing protein concentration (30-60 mg ml(-1)) and heating temperature (55-75 degrees C), but decreased with increasing pH (5.5-9.0). Low heating temperatures (50-55 degrees C) favoured the formation of more cohesive actomyosin gels than the higher heating temperatures (60-75 degrees C). Gels formed at low pH (5.5 and 6.0) were less cohesive than those formed at high pH (7.5-9.0). Addition of ATP and pyrophosphate (10 mm) prior to heating decreased gel strength and cohesiveness, whereas EDTA (1-5 mM) reduced gel strength but did not affect gel cohesiveness. PMID- 22059945 TI - Potential of electrospray mass spectrometry for meat pigment identification. AB - The potential of electrospray mass spectrometry (ESMS) to identify haem pigments from different species has been investigated. Purified haemoglobin and myoglobin from various sources (pig, beef, sheep and horse) were analysed by ESMS. The spectra showed ions corresponding to the molecular weights of the globin portions of the haemoproteins. When boiled and then analysed by ESMS, the globin chains remained intact but, on autoclaving for 1 h at 121 degrees C, partial hydrolysis was observed, although the fragments could still be used to identify the origin of the haemoglobin. ESMS is a rapid, sensitive technique and may have potential as an analytical method for meat speciation. PMID- 22059946 TI - Nitrite stabilization of lipids in cured pork. AB - Peroxidation studies indicated that phospholipids, microsomes and mitochondria from cured pork samples are less susceptible to metmyoglobin/hydrogen peroxide catalyzed peroxidation than their counterparts from nitrite-free pork samples. The reaction of phospholipids and polyunsaturated fatty acid ethyl esters with dinitrogen trioxide increased their stability to peroxidative changes. Phospholipids from cured pork and those lipids reacted with dinitrogen trioxide were capable of nitrosating a secondary amine. These data, together with infrared analyses, indicate that nitrite or dinitrogen trioxide reacts with unsaturated lipids to form nitro-nitroso derivatives, thus stabilizing the lipids toward peroxidation changes. This mechanism can, in part, explain the antioxidant role of nitrite in cured meats. PMID- 22059947 TI - Meat quality and muscle fibre type characteristics of Southdown Rams from high and low backfat selection lines. AB - Characteristics of the meat of 15-18-month Southdown rams from lines selected for high or low backfat depths (assessed ultrasonically at position C over the last rib) were compared. Half of the carcasses were electrically stimulated (ES) and within each carcass post-mortem treatments chosen to produce effects on meat tenderness were ageing periods of 1 or 15 days (Semimembranosus), early or delayed chilling (Biceps femoris), and trimming of the s.c. fat cover (Longissimus dorsi). These treatments had the expected effects on shear values, but the sizes of the effects were little affected by selection line or ES treatment. Selection line did not have any direct effects on shear values, reflectance values at several wavelengths, waterholding capacity, cooking loss or sarcomere length. The Semitendinosus muscle had a higher proportion of predominantly oxidative fibres for the high-backfat line, based on succinic dehydrogenase activity (P < 0.05), but there was no line difference in alkaline stable ATPase activity in the same muscle. Muscle fibre diameter was similar for the two lines. PMID- 22059948 TI - Further studies on n-nitrosopyrrolidine and its precursors: Effects of ascorbic acid and vitamin E on tumor development in mice as related to consumption of cured meat. AB - Two experiments were carried out to ascertain if supplementation of a semipurified diet to Swiss-ICR mice with either ascorbic acid (AA), vitamin E (Vit E) or a combination of the two would modulate the carcinogenic effects of N nitrosopyrrolidine (NPyr) and of its probable precursors (nitrite-N0(2) and pyrrolidine-Pyr) in Experiment I or of NPyr in Experiment II. Results indicated that neither AA nor Vit E modulated the carcinogenic effects of NPyr or of its probable precursors (NO(2) and Pyr). Results verified a previous report from our laboratory showing that NPyr increased the number of malignant tumors by some 5-8 fold over controls. There was a lower incidence of tumors in the control group on the semi-purfied diet than in the groups given NO(2) and Pyr, although both treatments had a low frequency of malignant tumors (1 63 versus 5 72 survivors). Results support our earlier study suggesting that neither NO(2) nor Pyr alone or in combination together contribute to cancer-at least in the laboratory mouse. PMID- 22059949 TI - Studies on thermostable antigens, production of species-specific antiadrenal sera and comparison of immunological techniques in meat speciation. AB - Heat-stable antigens (BE forms: resistant to heat and ethanol precipitation) of adrenal and muscle tissues of cattle, buffalo, sheep, goat and pig were prepared for use in detection of adulteration in meats. The physico-chemical characteristics of these antigens revealed that the antigens of adrenals had only one component corresponding to 'Troponin T'. Muscle antigens also contained a major troponin T component but were associated with low molecular weight fractions. Rabbit antiadrenal BE sera were developed and made species specific by immunoabsorption. The species-specific antisera were employed for identification of origin of fresh and cooked meats and their mixtures, using an immunodiffusion test-agar gel precipitation test (AGPT), counterimmunoelectrophoresis (CIEP), enzyme-linked immunosorbent assay (ELISA) and the unlabelled antibody peroxidase antiperoxidase (PAP) technique. The results indicated that absorbed antisera could successfully differentiate the fresh, cooked meats and the meat mixtures from the species under study. AGPT and CIEP were useful in identification of 5 10% addition, using water extracts of fresh meats and BE forms of cooked meats, whereas ELISA and PAP could detect adulteration down to the level of 1% when water extracts were used. Among the tests employed in the study, the PAP technique proved to be most sensitive. The antisera were also proved useful in identifying the species in canned meat products, milk, serum, plasma, semen, urine, organs, skin and spoilt flesh, employing AGPT and CIEP. PMID- 22059950 TI - Editorial. PMID- 22059951 TI - Assessment of exposure to Plasmodium falciparum transmission in a low endemicity area by using multiplex fluorescent microsphere-based serological assays. AB - BACKGROUND: The evaluation of malaria transmission intensity is a crucial indicator for estimating the burden of malarial disease. In this respect, entomological and parasitological methods present limitations, especially in low transmission areas. The present study used a sensitive multiplex assay to assess the exposure to Plasmodium falciparum infection in children living in an area of low endemicity. In three Senegalese villages, specific antibody (IgG) responses to 13 pre-erythrocytic P. falciparum peptides derived from Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, Csp and Pf11.1 proteins were simultaneously evaluated before (June), at the peak (September) and after (December) the period of malaria transmission, in children aged from 1 to 8 years. RESULTS: Compared to other antigens, a high percentage of seropositivity and specific antibody levels were detected with Glurp, Salsa1, Lsa3NR2, and Lsa1J antigens. The seropositivity increased with age for all tested antigens. Specific IgG levels to Glurp, Salsa1, Lsa3NR2, and Lsa1J were significantly higher in P. falciparum infected children compared to non-infected and this increase is significantly correlated with parasite density. CONCLUSION: The multiplex assay represents a useful technology for a serological assessment of rapid variations in malaria transmission intensity, especially in a context of low parasite rates. The use of such combined serological markers (i.e. Glurp, Lsa1, Lsa3, and Salsa) could offer the opportunity to examine these variations over time, and to evaluate the efficacy of integrated malaria control strategies. PMID- 22059952 TI - The emergence of complexity and restricted pleiotropy in adapting networks. AB - BACKGROUND: The emergence of organismal complexity has been a difficult subject for researchers because it is not readily amenable to investigation by experimental approaches. Complexity has a myriad of untested definitions and our understanding of its evolution comes primarily from static snapshots gleaned from organisms ranked on an intuitive scale. Fisher's geometric model of adaptation, which defines complexity as the number of phenotypes an organism exposes to natural selection, provides a theoretical framework to study complexity. Yet investigations of this model reveal phenotypic complexity as costly and therefore unlikely to emerge. RESULTS: We have developed a computational approach to study the emergence of complexity by subjecting neural networks to adaptive evolution in environments exacting different levels of demands. We monitored complexity by a variety of metrics. Top down metrics derived from Fisher's geometric model correlated better with the environmental demands than bottom up ones such as network size. Phenotypic complexity was found to increase towards an environment dependent level through the emergence of restricted pleiotropy. Such pleiotropy, which confined the action of mutations to only a subset of traits, better tuned phenotypes in challenging environments. However, restricted pleiotropy also came at a cost in the form of a higher genetic load, as it required the maintenance by natural selection of more independent traits. Consequently, networks of different sizes converged in complexity when facing similar environment. CONCLUSIONS: Phenotypic complexity evolved as a function of the demands of the selective pressures, rather than the physical properties of the network architecture, such as functional size. Our results show that complexity may be more predictable, and understandable, if analyzed from the perspective of the integrated task the organism performs, rather than the physical architecture used to accomplish such tasks. Thus, top down metrics emphasizing selection may be better for describing biological complexity than bottom up ones representing size and other physical attributes. PMID- 22059953 TI - Mycosis fungoides exhibiting features of a dermatofibroma: a case report and review of the literature. AB - We present the case of a 60-year-old male with known stage IA mycosis fungoides (MF) who developed a suspicious tumor within a pre-existing lymphomatous plaque of the right forearm. Microscopy revealed an unusual mixed fibrohistiocytic proliferation as well as atypical intraepidermal and dermal lymphocytes. There was no evidence of large-cell transformation. Histopathological, immunohistochemical and clinical clues suggest this lesion might not have represented a dermatofibroma, but rather a hitherto unreported dermatofibroma like process arising within a lesion of MF. The potential impact of this atypical lesion on the prognosis and clinical management of this patient highlights the importance of recognizing unusual clinical presentations of more common, benign lesions within this patient population. PMID- 22059954 TI - Helping children correctly say "I don't know" to unanswerable questions. AB - Adults ask children questions in a variety of contexts, for example, in the classroom, in the forensic context, or in experimental research. In such situations children will inevitably be asked some questions to which they do not know the answer, because they do not have the required information ("unanswerable" questions). When asked unanswerable questions, it is important that children indicate that they do not have the required information to provide an answer. These 2 studies investigated whether preinterview instructions (Experiment 1) or establishing a memory narrative (Experiment 2) helped children correctly indicate a lack of knowledge to unanswerable questions. In both studies, 6- and 8-year-olds participated in a classroom-based event about which they were subsequently interviewed. Some of the questions were answerable, and some were unanswerable. Results showed that preinterview instructions increased the number of younger children's appropriate "don't know" responses to unanswerable questions, without decreasing correct responses to answerable questions. This suggests that demand characteristics affect children's tendency correctly to say "I don't know." The opportunity to provide a narrative account increased children's appropriate "don't know" responses to unanswerable yes/no questions, and increased the number of younger children's correct responses to answerable questions. This suggests that cognitive factors also contribute to children's tendency correctly to say "I don't know." These results have implications for any context where adults need to obtain information from children through questioning, for example, a health practitioner asking about a medical condition, in classroom discourse, in the investigative interview, and in developmental psychology research. PMID- 22059955 TI - Insulin sensitisers in the treatment of non-alcoholic fatty liver disease: a systematic review. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely linked with obesity and the prevalence of NAFLD is about 17% to 33% in the Western world. There is a strong association of NAFLD with insulin resistance and, hence, insulin sensitisers have been tried. This systematic review examined the clinical effectiveness of insulin sensitisers in patients with NAFLD, to help decide whether or not a trial or trials of the insulin sensitisers was necessary and also to explore whether or not non-invasive alternatives to liver biopsy were available that could be used in a large trial of the insulin sensitisers. OBJECTIVE: To review the use of insulin sensitisers in the treatment of NAFLD. REVIEW METHODS: A systematic review of the clinical effectiveness of metformin, rosiglitazone and pioglitazone was carried out, including reviews and randomised controlled trials (RCTs). Databases searched were MEDLINE, 1950 to June 2010; EMBASE, 1980 to June 2010; Science Citation Index Expanded, June 2010; Conference Proceedings Citation Index - Science June 2010; The Cochrane Library 2005-10. Abstracts were screened independently by two researchers. A narrative review of diagnostic methods was conducted. RESULTS: Clinical effectiveness. We identified 15 RCTs (one available as abstract). Four papers explored efficacy of pioglitazone, one rosiglitazone, eight metformin; two compared metformin and rosiglitazone, although one used both metformin and rosiglitazone. The duration of most trials was between 6 and 12 months. Many trials had a small number of participants and the quality of the studies was mixed. Pioglitazone improved all parameters of liver histology. Metformin showed mixed results, with ultrasound changes in two studies showing some improvement in steatosis, whereas there were no changes in the other two. Metformin, however, showed no improvement in non alcoholic steatohepatitis (NASH) stages. Metformin showed greater reduction in glycosylated haemoglobin (-0.23% to -1.2% vs -0.2% to -0.7%) and fasting plasma glucose (+0.05 to -3.19 mmol/l vs -0.17 to -1.11 mmol/l) compared with pioglitazone. Metformin led to weight reduction (-4.3 to -6.7 kg), whereas participants on pioglitazone gained weight (+2.5 to +4.7 kg). Alanine aminotransferase levels were reduced with both metformin and pioglitazone; however, the reduction in levels with pioglitazone was not different to that caused by vitamin E. Most studies suggested that metformin led to a significant reduction in insulin resistance. Diagnosis. Non-invasive methods of diagnosing NAFLD without liver biopsy, using combinations of clinical history, laboratory tests and ultrasound, have been explored, but so far liver biopsy is the only proven method of distinguishing simple steatosis from NASH. Transient elastography appears useful, but less so in obese individuals. Magnetic resonance spectroscopy shows promise, but is expensive and not readily available. LIMITATIONS: Mixed quality of trials, with lack of detail as to how some trials were conducted. Many trials had small numbers of patients. CONCLUSIONS: The main need for drug trials is at the NASH stage. However, at present, any trial in the more advanced forms of NAFLD would have to use liver biopsy. The highest priority for research may, therefore, be in the diagnosis of NAFLD, and the differentiation between steatosis and NASH. The newer agents, the glucagon-like peptide-1 analogues such as liraglutide, may be more worthy of a trial. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 22059956 TI - A Toxoplasma gondii mutant highlights the importance of translational regulation in the apicoplast during animal infection. AB - Toxoplasma gondii is an obligate intracellular parasite of all warm-blooded animals. We previously described a forward genetic screen to identify T. gondii mutants defective in the establishment of a chronic infection. One of the mutants isolated was disrupted in the 3' untranslated region (3'UTR) of an orthologue of bacterial translation elongation factor G (EFG). The mutant does not have a growth defect in tissue culture. Genetic complementation of this mutant with the genomic locus of TgEFG restores virulence in an acute infection mouse model. Epitope tagged TgEFG localized to the apicoplast, via a non-canonical targeting signal, where it functions as an elongation factor for translation in the apicoplast. Comparisons of TgEFG expression constructs with wild-type or mutant 3'UTRs showed that a wild-type 3'UTR is necessary for translation of TgEFG. In tissue culture, the TgEFG transcript is equally abundant in wild-type and mutant parasites; however, during an animal infection, the TgEFG transcript is increased more than threefold in the mutant. These results highlight that in tissue culture, translation in the apicoplast can be diminished, but during an animal infection, translation in the apicoplast must be fully functional. PMID- 22059957 TI - Vitamin d and metabolic syndrome risk factors: evidence and mechanisms. AB - The metabolic syndrome develops in an individual with any three of the following risk factors: obesity, diabetes, inflammation, hypertension, dyslipidemia, and thrombosis. Recent evidence suggests that vitamin D may play a role in the development of some of these risk factors. The metabolic syndrome is more common in western societies than the underdeveloped countries. Individuals in western societies usually consume a high calorie diet that lacks essential nutrients and, by virtue of being located in the northern hemisphere, they have limited sun exposures which restrict their vitamin D synthesis. Moreover, the lifestyle of these societies is considered sedentary. These dietary and environmental factors coupled with the sedentary lifestyle predispose them to metabolic syndrome risk factors. Active research revealed the role of vitamin D in the development of obesity, diabetes, inflammation, and hypertension. On the other hand, limited research has been done on the role of vitamin D in other risk factors such as dyslipidemia and thrombosis. The scientific community proposes to increase the current vitamin D fortification level in foods to reduce the risk factors of the metabolic syndrome. PMID- 22059958 TI - Substitution of saturated fat in processed meat products: a review. AB - The food industry is increasingly directing its efforts to produce and commercialize functional foods where the reduction or even elimination of saturated fat is an important goal. This situation arises from the concern of many institutions and individuals worldwide on the growth of non-transmissible diseases, particularly cardiovascular ones. This article presents a revision of the most important research carried out on processed meat products production and looks at the topic from two principal points of view: the nutritional and technological function of fat and the way in which it is gradually being replaced in the above-mentioned products. Many ingredients have been used to substitute fat but while the results concerning the nutritional composition of the final products are generally acceptable, the sensory aspects are not completely solved. This review emphasizes the use of plastic fats because they allow the highest fat substitution levels during its process and consumption without affecting the product behavior. PMID- 22059959 TI - Application of ultra high pressure (UHP) in starch chemistry. AB - Ultra high pressure (UHP) processing is an attractive non-thermal technique for food treatment and preservation at room temperature, with the potential to achieve interesting functional effects. The majority of UHP process applications in food systems have focused on shelf-life extension associated with non-thermal sterilization and a reduction or increase in enzymatic activity. Only a few studies have investigated modifications of structural characteristics and/or protein functionalities. Despite the rapid expansion of UHP applications in food systems, limited information is available on the effects of UHP on the structural and physicochemical properties of starch and/or its chemical derivatives included in most processed foods as major ingredients or minor additives. Starch and its chemical derivatives are responsible for textural and physical properties of food systems, impacting their end-use quality and/or shelf-life. This article reviews UHP processes for native (unmodified) starch granules and their effects on the physicochemical properties of UHP-treated starch. Furthermore, functional roles of UHP in acid-hydrolysis, hydroxypropylation, acetylation, and cross-linking reactions of starch granules, as well as the physicochemical properties of UHP assisted starch chemical derivatives, are discussed. PMID- 22059960 TI - The stability and degradation of dietary DNA in the gastrointestinal tract of mammals: implications for horizontal gene transfer and the biosafety of GMOs. AB - The fate of dietary DNA in the gastrointestinal tract (GIT) of animals has gained renewed interest after the commercial introduction of genetically modified organisms (GMO). Among the concerns regarding GM food, are the possible consequences of horizontal gene transfer (HGT) of recombinant dietary DNA to bacteria or animal cells. The exposure of the GIT to dietary DNA is related to the extent of food processing, food composition, and to the level of intake. Animal feeding studies have demonstrated that a minor amount of fragmented dietary DNA may resist the digestive process. Mammals have been shown to take up dietary DNA from the GIT, but stable integration and expression of internalized DNA has not been demonstrated. Despite the ability of several bacterial species to acquire external DNA by natural transformation, in vivo transfer of dietary DNA to bacteria in the intestine has not been detected in the few experimental studies conducted so far. However, major methodological limitations and knowledge gaps of the mechanistic aspects of HGT calls for methodological improvements and further studies to understand the fate of various types of dietary DNA in the GIT. PMID- 22059961 TI - Antioxidants in food: mere myth or magic medicine? AB - The powerful action of antioxidants in preventing premature lipid oxidation in food suggests that the same compounds, when consumed with the daily diet, could unfold antioxidative/anti-aging effects in the human body. Therefore, it has been hypothesized that antioxidants are helpful in preventing various diseases. More detailed chemical and physiological examination of antioxidants shows, however, that the extrapolation of in vitro data to in vivo behavior may be misleading. Indeed, such a procedure fails to take into account the mismatch between most in vitro models (e.g., cell cultures) and in vivo systems. For example, the physiological relevance of pro-oxidative and other physiological activities of antioxidants have been largely underestimated. Actually, contrary to the antioxidant hypothesis, clinical trials testing the health benefits of dietary antioxidants have reported rather mixed or negative results. Many clinical studies have not taken into account the nutrikinetic and nutridynamic nature of antioxidants. Further, oxidative stress is not only an inevitable event in a healthy human cell, but responsible for the functioning of vital metabolic processes, such as insulin signaling and erythropoietin production. In the light of recent physiological studies it appears more advisable to maintain the delicate redox balance of the cell than to interfere with the antioxidant homeostasis by a non-physiological, excessive exogenous supply of antioxidants in healthy humans. PMID- 22059962 TI - Nutritional modulation of insulin resistance in the true carnivorous cat: a review. AB - Cats are strict carnivores that rely on nutrients in animal tissues to meet their specific and unique nutritional requirements. In their natural habitat, cats consume prey high in protein with moderate amounts of fat and minimal carbohydrates in contrast to commercial diets, which are sometimes moderate to high in carbohydrates. This change in diet has been accompanied by a shift from an outdoor environment to an indoor lifestyle and decreased physical activity, because cats no longer need to hunt to obtain food. This transformation of the lifestyle of cats is thought to be responsible for the recent increase in incidence of obesity, insulin resistance, and diabetes mellitus in domestic cats. At first, an overview of the evolutionary physiological adaptations of carbohydrate digestion in the feline digestive tract and of the hepatic carbohydrate and protein metabolism reflecting the true carnivorous nature of cats is given. Secondly, this literature review deals with nutritional modulation of insulin sensitivity, focusing on dietary macronutrients, carbohydrate sources, and dietary fiber for prevention and treatment of insulin resistance. PMID- 22059963 TI - Probiotic fermentation of plant based products: possibilities and opportunities. AB - Functional foods are claimed to have several health-specific advantages. In addition to their basic nutritive value, they contain a proper balance of ingredients which help in the prevention and treatment of illnesses and diseases. Within this category, products containing lactic acid bacteria or probiotics are increasingly gaining importance. The recognition of the beneficial effects of dairy products containing probiotics has been well established. The allergy to dairy products, lactose intolerance, and cholesterol content are the major drawbacks related to the use of fermented dairy products for a large percentage of consumers. Modern consumers are increasingly interested in their personal health, and expect the food that they eat to be healthy or even capable of preventing illness. Because of this, probiotic food products made out of fermentation of cereals and fruits and vegetables is receiving attention from the scientific world as well as consumers and constitutes the major part of this review. The use of mathematical models for the probiotic fermentation will help in reducing the time and effort involved in the optimization of the probiotic fermentation process. We have tried to summarize the developments in the use of mathematical models for probiotic fermentation. Future technological prospects exist in innovations which represent solutions for the stability and viability problems of probiotics in new food environments. Current research on novel probiotic formulations and microencapsulation technologies exploiting biological carrier and barrier materials has also been discussed. PMID- 22059964 TI - Polymerizable fluorescein derivatives: synthesis of fluorescent particles and their cellular uptake. AB - Fluorescent particles are used for a diverse number of biochemical assays including intracellular imaging, cellular tracking, as well as detection of a variety of biomolecules. They are typically prepared by postpolymerization conjugations of dyes onto preformed particles. Herein we report the synthesis of aminomethyl-functionalized fluorescent particles via the synthesis and application of polymerizable fluorescein monomers. These monomers allowed high and controllable fluorophore loading into the particles, resulting in enhanced fluorescence properties in comparison with more commonly used carboxyfluorescein conjugated particles. Furthermore, the particles were rapidly taken up by cells with enhanced fluorescence. The herein presented results demonstrate the advantages of dye polymerization in contrast with more conventional conjugation strategies for fluorescent particle generation with applications in the life sciences. PMID- 22059965 TI - The effect of cooking conditions on the eating quality of pork. AB - Two experiments were conducted to examine the effects of cooking parameters, including final internal temperature (65, 72.5 or 80 degrees C), on the eating quality of pork. Assessments were made by a 10-member trained taste panel. In Experiment 1 on loin steaks (m. longissimus) from 28 carcasses weighing 66 +/- 1.9 (SD) kg, increasing the final internal temperature from 65 to 80 degrees C had the following effects on mean scores (1-8): tenderness -1.0; juiciness -1.5, pork flavour +0.6 and abnormal flavour -0.5. The medium temperature of 72.5 degrees C was suggested as ideal. In Experiment 2 on leg roasts (m. gluteobiceps) from 96 carcasses weighing 65 + 2.7 (SD) kg, increasing the final internal temperature from 65 to 80 degrees C had the following effects on mean scores (1 8): tenderness -0.2 (not significant), juiciness -0.6, pork flavour +0.3 and abnormal flavour -0.5. The effects of final internal temperature were therefore smaller in roasts and temperatures towards the upper end of the range would be recommended for ideal eating quality, balancing small losses in tenderness and juiciness against gains in flavour scores. Although the experiments were not designed to examine source and sex effects there was evidence that tenderness can be improved through the use of Duroc genes and pelvic suspension of carcasses and no evidence of differences in eating quality between entire males and females. PMID- 22059966 TI - The effect of electrical head-only stun duration on electroencephalographic measured seizure and brain amino acid neurotransmitter release. AB - Effective electrical head-only stunning produces a seizure-like state followed by a period of analgesia seen in animals allowed to recover. Passing of a 1.0 A current (50 Hz, 500 V) for less than 0.2 s, through the head of a sheep does not produce a seizure-like state as evidenced by recorded electroencephalogram. Corresponding to this lack of seizure-like state, the release of the neurotransmitters glutamate and aspartate, in the brain, occurs to levels associated with arousal rather than seizure. At a duration of 0.2 s, the same stun parameters as above produce a seizure-like state and the release of glutamate and aspartate rises dramatically. The length of the seizure-like state, and the levels of release of glutamate, aspartate and a third neurotransmitter gamma amino-4-butyric acid (GABA), increased with stun duration until 4.0 s duration, where a peak in these parameters was seen. Stun durations of 2.0, 4.0, 8.0 and 12.0 s all produce similar effects. At a duration of 20 s, however, the length of the seizure-like state and the release of neurotransmitters is less than at shorter stun durations. For welfare purposes a head-only electrical stun, of 1.0 A, at a duration as low as 0.2 s produces unconsciousness and analgesia to subsequent slaughter procedures. However, maximum welfare benefits appear attainable at durations between 2.0 and 20.0 s. PMID- 22059967 TI - Influence of temperature variation on the metabolism of pig muscle in situ and after excision. AB - The experiment involved six halothane-positive (HP) and six halothane-negative (HN) pigs of about 100 kg liveweight. Under general anaesthesia the tibialis cranialis was exposed. The temperature of the muscle was maintained at either 35 or 40 degrees C (in situ). The muscle was stimulated via the peroneal nerve at 0.1 Hz for 10 min then 1 Hz for 10 further min. Twitch contractions were recorded throughout the stimulation, after which the muscle was excised and split into two parts which were kept in paraffin oil at either 35 or 40 degrees C (post-excision temperature) for 2 h. Samples were taken just before and after the 20 min stimulation period, and at 1 and 2 h after muscle excision for determination of pH and concentrations of PC, ATP, IMP, glycogen, G-6-P and lactate. As soon as one muscle was removed, the operation was repeated on the other leg. Both temperatures (35 and 40 degrees C) were applied to each animal in a balanced design. However data were obtained from only 11 pigs at 40 degrees C as one HP pig died accidentally at the beginning of the 40 degrees C experiment. Halothane sensitivity influenced the pH value and the levels of PC, G-6-P and lactate of the muscle in situ (P < 0.01 in all cases). Temperature affected contrction time (P < 0.01). Both halothane sensitivity and Post-excision temperature affected the pH values and the levels of PC, ATP, IMP, G-6-P and lactate (P < 0.01 in all cases) in the excised muscle. By contrast, the in situ temperature treatments did not affect any of the muscle traits measured after excision. It was concluded that the effects of the various treatments on the rate of metabolism in the excised muscle were wholly explainable in terms of temperature from the time of excision, and that the in situ temperature treatments may not be responsible for the differences after excision. PMID- 22059968 TI - Effect of the addition of pancreatic lipase on the ripening of dry-fermented sausages - Part 1. Microbial, physico-chemical and lipolytic changes. AB - The effect of the addition of nine different amounts (3-500 units) of pancreatic lipase on the microbial and physico-chemical parameters and lipid fractions during the ripening of dry fermented sausages has been studied. No differences between conventional and lipase-added sausages were found for pH, dry matter and water activity. The addition of lipase caused a greater accumulation of products resulting from the triglyceride breakdown, mainly diglycerides and free fatty acids (FFA). The maximum rate of lipolysis was observed during the first week of the ripening process, specially in the fermentation phase. The greater the pancreatic lipase added, the higher lipolysis observed. At the end of the ripening, the levels of total FFA were clearly higher (1.5 to 5-fold) in all lipase-added batches than in the controls. This fact gave rise to the accumulation of a great amount of FFA, which can contribute either by themselves to the flavour of the sausage or can be available as substrates for further transformations which may generate other flavour compounds. PMID- 22059969 TI - Tenderisation of pork as affected by degree of cold-induced shortening. AB - Porcine M. longissimus dorsi from 12 carcasses were used to study the effect of ante mortem exercise treatment, time of boning and different ageing periods on tenderness and tenderisation in pork. The pigs were randomly allocated into three groups, of which the pigs (in two of them) were exposed to work on a treadmill: (1) 30 min rest after work, then slaughtered; (2) slaughtered without rest after work; and (3) controls, which were not exposed to work before slaughter. At 1 and 6 h post-stunning, samples from right side of each carcass were excised and immediately chilled in icewater until 24 h post-stunning. The left side loins were used as controls and were chilled on the carcasses at 12-14 degrees C for 90 min and then at 2 degrees C before boning at 24 h post-stunning. The effect of ageing, 0 or 7 days at 2 degrees C, was studied. No parameter in this study was significantly affected by ante mortem treatment. WB shear force decreased significantly with increasing boning time and was correlated to the degree of muscle shortening in unaged excised samples. Muscle shortening for the 1 h excised cuts showed an average value of 27.4%, while an average value of only 6.1% was obtained for 6 h excised cuts. Ageing for 7 days resulted in only minor (7.3%) tenderness improvement for the 1 h excised cuts as compared to the 24.5% decrease in WB shear force obtained from the 6 h excised, less cold-shortened cuts. These differences in ageing rate, however, did not result in detectable changes in the degradation profile of myofibrillar proteins as analysed by SDS PAGE. PMID- 22059970 TI - Predictive value of slaughterhouse measurements of ultimate pork quality in seven halothane negative Yorkshire populations. AB - An experiment with 1969 pigs, belonging to Yorkshire sire lines, was set up in cooperation with seven Dutch breeding organizations. The pigs, which were claimed to be halothane negative, were slaughtered in weekly batches. Light reflectance was determined with the Hennessy Grading Probe (HGP) and Fibre Optic Probe (FOP), in addition to pH(1) and rigor mortis at 45 min post mortem (p.m.). Further meat quality determinations were performed either in the slaughterhouse at 20 h p.m., or in the laboratory at 24 h p.m.. At first sight, both the scatter of light (HGP PSE, FOP) and pH, measured at 45 min p.m., appeared to be indicative of the ultimate meat quality score. More accurate analyses, however, showed that the value of reflectance values is limited and less suitable in comparison to pH(1), especially with reference to the prediction of ultimate quality characteristics of water holding capacity. The correlations for pH(1) with drip loss were rather consistent, ranging from -0.34 to -0.52 per breeding population. In contrast, HGP reflectance values ranged from -0.27 to 0.34, while those based on FOP(1) had a range from nearly zero (0.02) to 0.20. The proportion of variation (R(2) * 100%) in drip loss, explained by a set of slaughterline measurements, ranged from 13 to about 28% per breeding population. The use of measurements carried out at 20 h p.m. improved the R(2) * 100% for drip loss to a range from 50 to 62%. PMID- 22059971 TI - Chilling pig carcasses: Effects on temperature, weight loss and ultimate meat quality. AB - Effects of conventional (4 degrees C, air velocity 0.5 m/s) and forced chilling at -5 degrees C (120 min) or -30 degrees C (30 min) with air velocities of 1, 2 or 4 m/s, followed by conventional chilling till 24 h post mortem on temperatures, meat quality and weight losses, were studied. Experiments were carried out in six batches of six slaughter pigs each (crossbred gilts, weighing 105-110 kg. The subcutaneous temperature decreased very rapidly to values below 0 degrees C when 'ultra' rapid chilling (-30 degrees C) at high air velocities (4 m/s was used. Immediately after rapid chilling, when the carcasses were railed into a conventional chiller, the subcutaneous temperature increased above the air temperature, after which the decline in temperature was continued. Temperature inside the biceps femoris muscle decreased from the start of chilling rather slowly according to an asymptotic curve until ultimate values of 4 degrees C were reached. Theoretically calculated temperatures during slaughter and chilling were comparable with the measured values; indicating that a finite-element calculation method in combination with a cylindrical model for heat transport can be used to predict muscle temperatures for various chilling regimes. Losses in carcass weight, 24 h after conventional and forced chilling at -5 degrees C, were about 2%. After 'ultra' rapid chilling (-30 degrees C) the losses were reduced to 1.3% when air velocity was increased to 4 m/s. Meat quality of the longissimus lumborum muscle was not significantly affected by the various chilling regimes except for the variables related to tenderness. The Warner-Bratzler shear forces were higher (P < 0.05) together with shorter sarcomere lengths (P < 0.10) after 'ultra' rapid chilling at a high (4 m/s) air velocity, indicating an increased risk of cold shortening. PMID- 22059972 TI - Differentiation between fresh and thawed meat by an enzyme profile test. AB - Exudates from fresh (stored at +4 degrees C) and thawed pork and beef (frozen and stored below -20 degrees C) was assayed by the rapid test kit API-ZYM(TM) to determine enzyme profiles. The test kit consists of 20 wells for different enzyme substrates. Of altogether 1040 results, only few reactions of the enzymes differed in their intensity between frozen and thawed pork or beef. Fresh pork showed a more intensive beta-galactosidase and N-acetyl-beta-glucosaminidase reaction while with fresh beef a more intensive reaction could only be detected for N-acetyl-beta-glucosaminidase. Only N-acetyl-beta-glucosaminidase showed significant differences between fresh and frozen meat in both species (alpha = 0.01). Considering the indistinct results of the test kit differentiation between frozen and thawed meat, the API-ZYM(TM) test kit is considered not suitable for distinguishing frozen from thawed pork or beef. PMID- 22059973 TI - Distribution of intramuscular lipid throughout M. longissimus thoracis et lumborum in Japanese Black, Japanese Shorthorn, Holstein and Japanese Black crossbreds. AB - Intramuscular lipid content of M. longissimus thoracis et lumborum was determined at five locations within the ribeye muscle from 267 Japanese Black, Japanese Shorthorn, Holstein and Japanese Black crossbred steers and heifers or cows in order to investigate the distribution of marbling. Breed was a highly significant (P < 0.001) source of variation for amount of marbling at each of the locations measured. Percentage of lipid was higher at the extremities of the muscle than in the middle part and was not affected by sex at any location except for opposite the 6th rib (P > 0.05). Regression equations were derived which relate the percentage of lipid at various locations within M. longissimus thoracis et lumborum to that opposite the 6th rib. A substantial portion of the variation in marbling observed at the other locations could be accounted for by marbling at the 6th rib (R(2) = 0.73-0.90). These data confirm that marbling varies within the ribeye muscle but suggest that it is rather consistent in the distribution pattern exhibited by Japanese Black cattle and their crosses. PMID- 22059974 TI - Structural and mechanical changes in raw and cooked single porcine muscle fibres extended to fracture. AB - Tensile tests on single muscle fibres from raw and cooked porcine longissimus thoracis muscle were performed to explore the structural mechanisms responsible for their deformation and fracture properties. Measurements of load and deformation were made simultaneously with light microscopy observations of the structural changes which occur on extension. On extending the fibres to fracture, an r-shaped stress-strain curve was observed and the structural changes which occurred during this process could be divided into three phases. Phase one, was characterised by a rapid increase in stress with little change in strain and ended at the yield point. Sarcomere length was uniform along the fibre in this initial phase. Raw fibres yielded at strains of between 2 and 5% of their resting lengths and cooked fibres at strains of between 10 and 20%. In phase two, there was rapid increase in strain with minimal changes in stress. In most fibres this phase was characterised by multiple cracks on the fibre surface and unequal sarcomere stretching. Sarcomeres in the regions where the surface had ruptured extended faster than those in areas still covered by the surface membrane, where sarcomere length remained relatively unchanged. In some cooked fibres, there was little or no surface cracking and all the sarcomeres in these fibres extended almost uniformly. Phase three was characterised by a rise in stress as strain increased and then a final fall in stress at the breaking point. This was accompanied by myofibrillar failure and finally breakage of the whole fibre. The myofibrils did not always fail as one unit; a progressive snapping of small bundles of myofibrils was seen in some raw fibres. Muscle fibres could be stretched to 10.9 +/- 1.45% of their resting length before breaking when raw, but to 130 +/- 42% of their rest lengths after they were cooked for 1 h at 80 degrees C. Where multiple surface cracking was observed in phase two, sarcomeres in some cracked areas lengthened faster than others and the cracked areas which extended fastest were usually the focus of the eventual failure of the fibre. In raw fibres, sarcomeres in the areas where the fibre surface had ruptured could be stretched up to 107.7% before failure, while those in areas of the fibre with an intact surface remained relatively unchanged. In cracked areas of cooked fibres the sarcomeres were more extensible and could be stretched to 169.7% before breaking. The order-of-magnitude increase in overall extension to failure of fibres resulting from cooking is only partially due to this increase in sarcomere extensibility in cracked areas. Mechanically demembranating raw fibres depressed the stress at which yielding occurred and doubled their breaking strain. However, this process had no effect on the stress at which the fibres fractured. The results show that deformation is not uniform along individual fibres, especially in the raw case and that the endomysium has an important contribution to this non uniform deformation. PMID- 22059975 TI - Influence of storage time on parameters of colour stability of beef. AB - Direct measurements of the oxygen partial pressure profiles at the surface of the longissimus dorsi muscle of six bulls were obtained by means of a solid-state probe after 1 min and 5 h exposure to air at 5 degrees C. Changes in muscle colour were examined at the same time. The results show the profiles of oxygen partial pressure at the muscle surface after differing storage times (1, 3, 5, 7, 11 and 13 days at 5 degrees C). Up to 5 days post mortem, increases in oxygen partial pressure with lengthening storage periods also led to higher percentages of oxymyoglobin, following exposure to air 1 min to 5 h. Further storage for up to 13 days decreased oxygenation, despite higher oxygen partial pressures. There was no evidence of rapid autoxidation to metmyoglobin during a 5-h period of exposure to air. Obvious connections between oxygenation and measurements of a value were not found. The Lab-values increased dependent on the length of storage time. PMID- 22059976 TI - Influence on meat colour of spray-chilling the surface of pig carcasses. AB - The present study examines the influence of spray-chilling on the surface colour of the musculature, skin and spinal spongiosa of swine carcass halves. Thirty swine halves, of the commercial classification U, were divided into six experimental groups and chilled under varying conditions over a period of 20 h. Three of the experimental groups were sprayed periodically with 810 g drinking water within a 4-h chilling phase. The other three served as unsprayed control groups. Oxygenation of the myoglobin to oxymyoglobin was accelerated by spraying the surface of the musculature. Spray-chilling conditions had no influence on the formation of metmyoglobin. The colour of the sprayed ham musculature became lighter after 4 h of chilling. Red- and yellow-values decreased. There were no significant differences in the colour values after 20 h of chilling. The surface of the skin became lighter after spray-chilling. The spraying had no influence on the colour of the spinal spongiosa. PMID- 22059977 TI - The relationship between carcass, meat and eating quality of three pig genotypes. AB - The relation between the intrinsic carcass and meat quality and the organoleptical characteristics of three genotypes of pigs was studied. In total 411 pigs, consisting of 121 BL-genotype pigs, 115 hybrids (Seghers Hybrid) and 175 Large White-genotype pigs, were screened. Slaughter day and genetic background had a great impact on the intrinsic meat quality parameters. The factor 'slaughter day' implies the stunning method besides the total specific transport and slaughter conditions. Whatever the genetic background is, halothane susceptibility is obviously the crucial factor. Selection against the halothane gene positively influences the intrinsic and sensory meat quality parameters. This study also suggests that an increase in the intramuscular fat content, if desirable in the interest of the sensory meat quality, can be achieved without deterioration of the zoo-technical performance and the carcass quality of the pigs. PMID- 22059978 TI - The effect of transport on some metabolic parameters and meat quality in pigs. AB - Two groups of 40 castrated male pigs were selected at random in an abattoir from pigs arriving from two farms, situated 650 km (group A) and 180 km (group B) from the plant, respectively. The animals were kept in lairage overnight and slaughtered the following morning. At slaughter, samples of blood were collected to determine serum levels of some enzymes [lactic dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT) and glutamic phosphatase transaminase (GPT)]. Measurements of pH were then taken on the Longissimus thoracis at the level of the last rib 45 min, 3 h and 24 h post mortem. After overnight chilling of the sides at +2 degrees C, a portion of the Longissimus thoracis was removed for colour and drip measurements. Results show that distance travelled affects pH values at 45 min and 24 h, group A presenting higher values than group B (P < 0.001). Drip loss did not differ significantly between the two groups, while group A showed lower values of L (*) and higher a (*) values than group B (P < 0.05 and P < 0.01, respectively), with no differences in the mean values of b (*). In group A, a higher value of LDH was observed (P < 0.001) than in group B. GOT and GPT showed no significant difference between the two groups. It is concluded that, although some significant effects of treatment were recorded on some quality traits, the magnitude of the differences are not considered of much practical significance. PMID- 22059979 TI - Formation of oxo- and hydroxyfatty acids in irradiated chickens. AB - Finely ground chicken skin and subcutaneous fat exposed to gamma radiation from (137)Cs at 0-2 degrees C for up to 10 kGy generated oxofatty acids (OFA) and hydroxyfatty acids (HFA) in the glycerides. Both classes were determined as colored derivatives; OFA as 2,4-dinitrophenylhydrazones, and HFA as esters of pyruvic acid 2,6-dinitrophenylhydrazone. The concentration of OFA increased with increasing irradiation dose but not always linearly. Variations in the concentration of both classes were noted and some chicken lipids failed to form both classes. In the samples where OFA were generated in significant quantities, the absorption maximum of the derivatives shifted toward a higher wavelength with increasing dose due ostensibly to the formation of double bond(s) in conjugation with the oxo group. This shift in absorption maximum was initially considered to be a means for detecting irradiation as well as indicating the dose received with fair accuracy. However, in several instances irradiation of a chicken sample did not result in the formation of significant increases in OFA and therefore this method cannot be used as a definitive test. PMID- 22059980 TI - Biological effects and adaptive response from single and repeated computed tomography scans in reticulocytes and bone marrow of C57BL/6 mice. AB - This study investigated the biological effects and adaptive responses induced by single and repeated in vivo computed tomography (CT) scans. We postulated that, through the induction of low-level oxidative stress, repeated low-dose CT scans (20 mGy, 2 days/week, 10 weeks) could protect mice (C57BL/6) from acute effects of high-dose radiation (1 Gy, 2 Gy). The micronucleated reticulocyte (MN-RET) count increased linearly after exposure to single CT scans of doses ranging from 20 to 80 mGy (P = 0.033). Ten weeks of repeated CT scans (total dose 400 mGy) produced a slight reduction in spontaneous MN-RET levels relative to levels in sham CT-scanned mice (P = 0.04). Decreases of nearly 10% in gamma-H2AX fluorescence levels were observed in the repeated CT-scanned mice after an in vitro challenge dose of 1 Gy (P = 0.017) and 2 Gy (P = 0.026). Spontaneous apoptosis levels (caspase 3 and 7 activation) were also significantly lower in the repeated CT-scanned mice than the sham CT-scanned mice (P < 0.01). In contrast, mice receiving only a single CT scan showed a 19% elevation in apoptosis (P < 0.02) and a 10% increase in gamma-H2AX fluorescence levels after a 2-Gy challenge (P < 0.05) relative to sham CT controls. Overall, repeated CT scans seemed to confer resistance to larger doses in mice, whereas mice exposed to single CT scans exhibited transient genotoxicity, enhanced apoptosis, and characteristics of radiation sensitization. PMID- 22059981 TI - The disaster at Japan's Fukushima-Daiichi nuclear power plant after the March 11, 2011 earthquake and tsunami, and the resulting spread of radioisotope contamination. AB - On March 11, 2011 eastern Japan was struck by a magnitude 9.0 earthquake and an enormous tsunami, over 13 m in height, which together killed over 20,500 people and resulted in the evacuation of over 320,000 people from the devastated areas. This paper describes the damage sustained by the Fukushima-Daiichi nuclear power plant during this unpredicted major natural disaster and the events that happened in the months after this accident. The events occurring at the Fukushima-Daiichi nuclear power plant, the actions taken to minimize the effects of the damage to the plant and to protect the public, and the points at which the responses proved to be inadequate all offer lessons that will be of value to those planning for and responding to future natural disasters and accidents in Japan and around the world. PMID- 22059982 TI - A case of HER-2-positive recurrent breast cancer showing a clinically complete response to trastuzumab-containing chemotherapy after primary treatment of triple negative breast cancer. AB - We report a case of HER-2-positive recurrent breast cancer showing a clinically complete response to trastuzumab-containing chemotherapy 6 years after primary treatment of triple-negative breast cancer. The primary tumor was negative for HER-2 as determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) (1+, and ratio, 1.1), but examination of the recurrent lymph node metastasis showed positivity for HER-2 by FISH (ratio, 5.2). No lesions were detected in either her left breast or in other organs, and the patient was diagnosed as having HER-2-positive recurrent disease. Combination chemotherapy using weekly paclitaxel and trastuzumab was initiated, and a clinically complete response was achieved. This report suggests the benefit of routine evaluation of HER-2 status in recurrent breast cancer with the introduction of HER-2-targeting agents. PMID- 22059983 TI - Thiazolides as novel antiviral agents. 2. Inhibition of hepatitis C virus replication. AB - We report the activities of a number of thiazolides [2-hydroxyaroyl-N-(thiazol-2 yl)amides] against hepatitis C virus (HCV) genotypes IA and IB, using replicon assays. The structure-activity relationships (SARs) of thiazolides against HCV are less predictable than against hepatitis B virus (HBV), though an electron withdrawing group at C(5') generally correlates with potency. Among the related salicyloylanilides, the m-fluorophenyl analogue was most promising; niclosamide and close analogues suffered from very low solubility and bioavailability. Nitazoxanide (NTZ) 1 has performed well in clinical trials against HCV. We show here that the 5'-Cl analogue 4 has closely comparable in vitro activity and a good cell safety index. By use of support vector analysis, a quantitative structure-activity relationship (QSAR) model was obtained, showing good predictive models for cell safety. We conclude by updating the mode of action of the thiazolides and explain the candidate selection that has led to compound 4 entering preclinical development. PMID- 22059984 TI - Bioconjugation of protein-repellent zwitterionic polymer brushes grafted from silicon nitride. AB - A new method for attaching antibodies to protein-repellent zwitterionic polymer brushes aimed at recognizing microorganisms while preventing the nonspecific adsorption of proteins is presented. The poly(sulfobetaine methacrylate) (SBMA) brushes were grafted from alpha-bromo isobutyryl initiator-functionalized silicon nitride (Si(x)N(4), x >= 3) surfaces via controlled atom-transfer radical polymerization (ATRP). A trifunctional tris(2-aminoethyl)amine linker was reacted with the terminal alkylbromide of polySBMA chains. N-Hydroxysuccinimide (NHS) functionalization was achieved by reacting the resultant amine-terminated polySBMA brush with bifunctional suberic acid bis(N-hydroxysuccinimide ester). Anti-Salmonella antibodies were subsequently immobilized onto polySBMA-grafted Si(x)N(4) surfaces through these NHS linkers. The protein-repellent properties of the polySBMA-grafted surface after antibody attachment were evaluated by exposing the surfaces to Alexa Fluor 488-labeled fibrinogen (FIB) solution (0.1 g.L(-1)) for 1 h at room temperature. Confocal laser scanning microscopy (CLSM) images revealed the minimal adsorption of FIB onto the antibody-coated polySBMA in comparison with that of antibody-coated epoxide monolayers and also bare Si(x)N(4) surfaces. Subsequently, the interaction of antibodies immobilized onto polySBMA with SYTO9-stained Salmonella solution without using blocking solution was examined by CLSM. The fluorescent images showed that antibody-coated polySBMA efficiently captured Salmonella with only low background noise as compared to antibody-coated monolayers lacking the polymer brush. Finally, the antibody coated polySBMA surfaces were exposed to a mixture of Alexa Fluor 647-labeled FIB and Salmonella without the prior use of a blocking solution to evaluate the ability of the surfaces to capture bacteria while simultaneously repelling proteins. The fluorescent images showed the capture of Salmonella with no adsorption of FIB as compared to antibody-coated epoxide surfaces, demonstrating the potential of the zwitterionic layer in preventing the nonspecific adsorption of the proteins during the detection of bacteria in complex matrices. PMID- 22059986 TI - Tracking of the polyproline folding by density functional computations and Raman optical activity spectra. AB - Polyprolines offer many opportunities to study factors influencing peptide and protein folding and structure. Longer chains can adopt two well-defined forms (PPI and PPII), but shorter peptides are quite flexible. To understand in detail the dependence of the secondary structure on the length and the interplay between the side chain and main chain conformation, zwitterionic (Pro)(N) models (with N = 2, 3, 4, 6, 9, 12 and longer inhomogeneous chains) were studied by a combination of the Raman and Raman optical activity (ROA) spectroscopy with the density functional theory (DFT). Potential surfaces were systematically explored for the shorter oligoprolines, and Boltzmann conformational ratios were obtained both for the main chain and the proline ring puckering. The predictions were verified by comparison of the experimental and simulated ROA spectra. The conformer ratios extracted from a decomposition of the experimental ROA into scaled computed spectra well reproduced Boltzmann populations calculated from relative energies. For example, an "A" puckering of the proline ring was found prevalent, relatively independent of the length, whereas the cis-amide backbone form adopted by shorter peptides rapidly disappeared for N > 4. The results are consistent with previous NMR and vibrational circular dichroism (VCD) data. Delocalized exciton vibrations along the peptide chain often enhance the ROA signal, and can thus be used to indicate a longer regular peptide structure. The ROA technique appeared to be very sensitive to the ring puckering; less distinct spectral features were produced by changes in the main chain geometry. PMID- 22059985 TI - Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. AB - Plant cell culture systems were initially explored for use in commercial synthesis of several high-value secondary metabolites, allowing for sustainable production that was not limited by the low yields associated with natural harvest or the high cost associated with complex chemical synthesis. Although there have been some commercial successes, most notably paclitaxel production from Taxus sp., process limitations exist with regards to low product yields and inherent production variability. A variety of strategies are being developed to overcome these limitations including elicitation, in situ product removal and metabolic engineering with single genes and transcription factors. Recently, the plant cell culture production platform has been extended to pharmaceutically active heterologous proteins. Plant systems are beneficial because they are able to produce complex proteins that are properly glycosylated, folded and assembled without the risk of contamination by toxins that are associated with mammalian or microbial production systems. Additionally, plant cell culture isolates transgenic material from the environment, allows for more controllable conditions over field-grown crops and promotes secretion of proteins to the medium, reducing downstream purification costs. Despite these benefits, the increase in cost of heterologous protein synthesis in plant cell culture as opposed to field-grown crops is significant and therefore processes must be optimized with regard to maximizing secretion and enhancing protein stability in the cell culture media. This review discusses recent advancements in plant cell culture processing technology, focusing on progress towards overcoming the problems associated with commercialization of these production systems and highlighting recent commercial successes. PMID- 22059987 TI - Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjogren's syndrome. AB - Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by a progressive oral and ocular dryness that correlates poorly with the autoimmune damage of the glands. It has been proposed that a loss of homeostatic equilibrium in the glands is partly responsible for salivary dysfunction with acinar cells involved actively in the pathogenesis of SS. The non-obese diabetic (NOD) mouse model of Sjogren's syndrome develops secretory dysfunction and early loss of glandular homeostatic mechanisms, with mild infiltration of the glands. Based on the vasodilator, prosecretory and trophic effects of the vasoactive intestinal peptide (VIP) on acini as well as its anti-inflammatory properties we hypothesized that the local expression of VIP/vasoactive intestinal peptide receptor (VPAC) system in salivary glands could have a role in acinar cell apoptosis and macrophage function thus influencing gland homeostasis. Here we show a progressive decline of VIP expression in submandibular glands of NOD mice with no changes in VPAC receptor expression compared with normal mice. The deep loss of endogenous VIP was associated with a loss of acinar cells through apoptotic mechanisms that could be induced further by tumour necrosis factor (TNF)-alpha and reversed by VIP through a cyclic adenosine-5'-monophosphate (cAMP)/protein kinase A (PKA)-mediated pathway. The clearance of apoptotic acinar cells by macrophages was impaired for NOD macrophages but a shift from inflammatory to regulatory phenotype was induced in macrophages during phagocytosis of apoptotic acinar cells. These results support that the decline in endogenous VIP/VPAC local levels might influence the survival/apoptosis intracellular set point in NOD acinar cells and their clearance, thus contributing to gland homeostasis loss. PMID- 22059988 TI - Detection of four diabetes specific autoantibodies in a single radioimmunoassay: an innovative high-throughput approach for autoimmune diabetes screening. AB - Highly sensitive and specific radioimmunoassays have been validated for autoantibodies reacting with the four major autoantigens identified so far in autoimmune diabetes. However, the analysis of this large number of autoantigens has increased the costs and time necessary for complete autoantibody screenings. Our aim was to demonstrate that it is possible to detect the immunoreactivity against a combination of four different autoantigens by a single assay, this representing a rapid, low-cost first approach to evaluate humoral autoimmunity in diabetes. By using this novel multi-autoantigen radioimmunoassay (MAA), in subsequent steps we analysed 830 sera, 476 of known and 354 of unknown diabetes specific immunoreactivity, collected from various groups of individuals including type 1 and type 2 diabetes patients, autoantibody-positive patients with a clinical diagnosis of type 2 diabetes (LADA), prediabetic subjects, individuals at risk to develop autoimmune diabetes, siblings of type 1 diabetic patients, coeliac patients and healthy control subjects. All sera reacting with one or more of the four autoantigens by single assays also resulted positive with MAA, as well as eight of 24 type 1 diabetic patients classified initially as autoantibody negative at disease onset based on single autoantibody assays. In addition, MAA showed 92% sensitivity and 99% specificity by analysing 140 blinded sera from type 1 diabetic patients and control subjects provided in the 2010 Diabetes Autoantibody Standardization Program. MAA is the first combined method also able to evaluate, in addition to glutamic acid decarboxylase (GAD) and tyrosine phosphatase (IA)-2, insulin and islet beta-cell zinc cation efflux transporter (ZnT8) autoantibodies. It appears to be particularly appropriate as a first-line approach for large-scale population-based screenings of anti-islet autoimmunity. PMID- 22059989 TI - 2alpha-Methyl-19-nor-(20S)-1,25-dihydroxyvitamin D(3) protects the insulin 2 knockout non-obese diabetic mouse from developing type 1 diabetes without hypercalcaemia. AB - Type 1 diabetes (T1D) is an autoimmune disease that destroys the insulin producing beta-islet cells of the pancreas. Currently, there are no treatment modalities for prevention of T1D, and the mechanisms influencing disease inception and early progression are not well understood. We have used the insulin 2(-/-) non-obese diabetic (Ins2(-/-) NOD) model to study stages of T1D and to examine the protective effects of a potent analogue of 1alpha,25-dihydroxyvitamin D(3), 2alpha-methyl-19-nor-(20S)-1alpha,25-dihydroxyvitamin D(3) (2AMD). Pancreatic tissues from control and 2AMD-treated Ins2(-/-) NOD mice were obtained weekly from 5 to 16 weeks of age. Using immunohistochemical (IHC) analysis, samples were analysed for changes in beta cell survival, islet structure and T cell invasion. Weekly intraperitoneal glucose tolerance tests (IPGTT) were performed to assess comparative beta cell function in control and treated animals. IHC demonstrated progressive beta cell destruction in control mice. In contrast, 2AMD treatment preserved islet cell architecture, arrested intra-islet T cell invasion and prevented the transition from insulitis to diabetes. IPGTT results revealed progressive impairment of beta cell function with increasing age in control mice, while 2AMD treatment resulted in normal beta function throughout the study. These results demonstrate that the Ins2(-/-) NOD model provides a rapid and effective method for studying T1D and for assessing efficacy of anti diabetic agents. PMID- 22059990 TI - The major risk alleles of age-related macular degeneration (AMD) in CFH do not play a major role in rheumatoid arthritis (RA). AB - Because activation of the alternative pathway (AP) of the complement system is an important aspect of both age-related macular degeneration (AMD) and rheumatoid arthritis (RA), we wished to address the question whether genetic risk factors of the AP inhibitor complement factor H (CFH) for AMD would also be risk factors for RA. For this purpose we genotyped single nucleotide polymorphisms (SNPs) in a Dutch set of RA patients and controls. Similarly, a meta-analysis using a Spanish cohort of RA as well as six large genome-wide association studies (GWAS) studies was performed. For these SNPs we analysed more than 6000 patients and 20,000 controls. The CFH variants, I62V, Y402H, IVS1 and IVS10, known to associate strongly with AMD, did not show a significant association with the risk of developing RA despite a strong statistical power to detect such differences. In conclusion, the major risk alleles of AMD in CFH do not have a similar effect on developing RA. PMID- 22059991 TI - Role of tumour necrosis factor (TNF)-alpha and TNFRSF1A R92Q mutation in the pathogenesis of TNF receptor-associated periodic syndrome and multiple sclerosis. AB - It has long been known that tumour necrosis factor (TNF)/TNFRSF1A signalling is involved in the pathophysiology of multiple sclerosis (MS). Different genetic and clinical findings over the last few years have generated renewed interest in this relationship. This paper provides an update on these recent findings. Genome-wide association studies have identified the R92Q mutation in the TNFRSF1A gene as a genetic risk factor for MS (odds ratio 1.6). This allele, which is also common in the general population and in other inflammatory conditions, therefore only implies a modest risk for MS and provides yet another piece of the puzzle that defines the multiple genetic risk factors for this disease. TNFRSF1A mutations have been associated with an autoinflammatory disease known as TNF receptor associated periodic syndrome (TRAPS). Clinical observations have identified a group of MS patients carrying the R92Q mutation who have additional TRAPS symptoms. Hypothetically, the co-existence of MS and TRAPS or a co-morbidity relationship between the two could be mediated by this mutation. The TNFRSF1A R92Q mutation behaves as a genetic risk factor for MS and other inflammatory diseases, including TRAPS. Nevertheless, this mutation does not appear to be a severity marker of the disease, neither modifying the clinical progression of MS nor its therapeutic response. An alteration in TNF/TNFRS1A signalling may increase proinflammatory signals; the final clinical phenotype may possibly be determined by other genetic or environmental modifying factors that have not yet been identified. PMID- 22059992 TI - Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1beta in idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive interstitial lung disease of unknown aetiology. Interleukin (IL)-1beta plays an important role in inflammation and has been associated with fibrotic remodelling. We investigated the balance between IL-1beta and IL-1 receptor antagonist (IL-1Ra) in bronchoalveolar lavage fluid (BALF) and serum as well as the influence of genetic variability in the IL1B and IL1RN gene on disease susceptibility and cytokine levels. In 77 IPF patients and 349 healthy controls, single nucleotide polymorphisms (SNPs) in the IL1RN and IL1B genes were determined. Serum and BALF IL-1Ra and IL-1beta levels were measured using a multiplex suspension bead array system and were correlated with genotypes. Both in serum and BALF a significantly decreased IL-1Ra/IL-1beta ratio was found in IPF patients compared to healthy controls. In the IL1RN gene, one SNP was associated with both the susceptibility to IPF and reduced IL-1Ra/IL-1beta ratios in BALF. Our results show that genetic variability in the IL1RN gene may play a role in the pathogenesis of IPF and that this role may be more important than thought until recently. The imbalance between IL-1Ra and IL-1beta might contribute to a proinflammatory and pro fibrotic environment in their lungs. PMID- 22059993 TI - Neutralization of mitogenic lectins by intravenous immunoglobulin (IVIg) prevents T cell activation: does IVIg really have a direct effect on T cells? AB - Intravenous immunoglobulin (IVIg) is used for the treatment of an increasing number of autoimmune diseases. Clinical observations on IVIg-treated patients have revealed a modulation of T cell populations and functions in these patients. In vitro studies aimed at understanding the mechanisms underlying the effects of IVIg on T cells led to the conclusion that IVIg directly affected lectin activated T cell functions. However, more recent studies have suggested the absence of a direct effect of IVIg on T cells. In the present work, we revisited the effect of IVIg on T cells using lectin-stimulated human T cells and showed that IVIg inhibited T cell functions only when added simultaneously with the activating lectin. Further, we showed that IVIg depleted from lectin-reactive IgG was no longer inhibitory, suggesting that the effect of IVIg on T cells was the consequence of lectin neutralization, possibly by interaction with glycans present in F(ab')(2) portion of IgG molecules. Our results challenge the previously widely accepted notion that IVIg exerts its anti-inflammatory effects by acting directly on T cells and suggest that effects of IVIg observed in treated patients are rather a consequence of the recently reported inhibitory effect of IVIg on antigen presentation. PMID- 22059994 TI - Differential inhibition of trastuzumab- and cetuximab-induced cytotoxicity of cancer cells by immunoglobulin G1 expressing different GM allotypes. AB - Antibody-dependent cell-mediated cytotoxicity (ADCC), which links the innate and the adaptive arms of immunity, is a major host immunosurveillance mechanism against tumours, as well as the leading mechanism underlying the clinical efficacy of therapeutic antibodies such as cetuximab and trastuzumab, which target tumour antigens, human epidermal growth factor receptor (HER)1 and HER2, respectively. Immunoglobulin (Ig)G antibody-mediated ADCC is triggered upon ligation of Fcgamma receptor (FcgammaR) to the Fc region of IgG molecules. It follows that genetic variation in FcgammaR and Fc could contribute to the differences in the magnitude of ADCC. Genetic variation in FcgammaR is known to contribute to the differences in the magnitude of ADCC, but the contribution of natural genetic variation in Fc, GM allotypes, in this interaction has hitherto not been investigated. Using an ADCC inhibition assay, we show that IgG1 expressing the GM 3+, 1-, 2- allotypes was equally effective in inhibiting cetuximab- and trastuzumab-mediated ADCC of respective target cells, in the presence of natural killer (NK) cells expressing either valine or phenylalanine allele of FcgammaRIIIa. In contrast, IgG1 expressing the allelic GM 17+, 1+, 2+ allotypes was significantly more effective in inhibiting the ADCC - mediated by both monoclonal antibodies - when NK cells expressed the valine, rather than the phenylalanine, allele of FcgammaRIIIa. These findings have important implications for engineering antibodies (with human gamma1 constant region) against malignancies characterized by the over-expression of tumour antigens HER1 and HER2 - especially for patients who, because of their FcgammaRIIIa genotype, are unlikely to benefit from the currently available therapeutics. PMID- 22059995 TI - An engineered Plasmodium falciparum C-terminal 19-kilodalton merozoite surface protein 1 vaccine candidate induces high levels of interferon-gamma production associated with cellular immune responses to specific peptide sequences in Gambian adults naturally exposed to malaria. AB - The 19-kDa C-terminal region of merozoite surface protein 1 (MSP1(19)), a major blood stage malaria vaccine candidate, is the target of cellular and humoral immune responses in humans naturally infected with Plasmodium falciparum. We have previously described engineered variants of this protein, designed to be better vaccine candidates, but the human immune response to these proteins has not been characterized fully. Here we have investigated the antigenicity of one such variant compared to wild-type MSP1(19)-derived protein and peptides. Gambian adults produced both high T helper type 1 (Th1) [interferon (IFN)-gamma] and Th0/Th2 [interleukin (IL)-13 and sCD30] responses to the wild-type MSP1(19) and the modified protein as wells as to peptides derived from both forms. Response to the modified MSP1(19) (with three amino acid substitutions: Glu27Tyr, Leu31Arg and Glu43Leu) relative to the wild-type, included higher IFN-gamma production. Interestingly, some peptides evoked different patterns of cytokine responses. Modified peptides induced higher IL-13 production than the wild-type, while the conserved peptides P16 and P19 induced the highest IFN-gamma and IL-13 and/or sCD30 release, respectively. We identified P16 as the immunodominant peptide that was recognized by cells from 63% of the study population, and not restricted to any particular human leucocyte antigen D-related (HLA-DR) type. These findings provide new and very useful information for future vaccine development and formulation as well as potential Th1/Th2 immunmodulation using either wild-type or modified protein in combination with their peptides. PMID- 22059996 TI - Sildenafil treatment attenuates lung and kidney injury due to overproduction of oxidant activity in a rat model of sepsis: a biochemical and histopathological study. AB - Sepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on caecal ligation and puncture (CLP)-induced sepsis in rats. Four groups of rats were used, each composed of 10 rats: (i) 10 mg/kg SLD-treated CLP group; (ii) 20 mg/kg SLD treated CLP group; (iii) CLP group; and (iv) sham-operated control group. A CLP polymicrobial sepsis model was applied to the rats. All groups were killed 16 h later, and lung, kidney and blood samples were analysed histopathologically and biochemically. Sildenafil increased glutathione (GSH) and decreased the activation of myeloperoxidase (MPO) and of lipid peroxidase (LPO) and levels of superoxide dismutase (SOD) in the septic rats. We observed a significant decrease in LPO and MPO and a decrease in SOD activity in the sildenafil-treated CLP rats compared with the sham group. In addition, 20 mg/kg sildenafil treatment in the sham-operated rats improved the biochemical status of lungs and kidneys. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups, except the CLP + sildenafil 10 mg/kg group. The CLP + sildenafil 20 mg/kg group had the lowest inflammation score. Sildenafil treatment decreased the serum tumour necrosis factor (TNF) alpha level when compared to the CLP group. Our results indicate that sildenafil is a highly protective agent in preventing lung and kidney damage caused by CLP induced sepsis via maintenance of the oxidant-anti-oxidant status and decrease in the level of TNF-alpha. PMID- 22059997 TI - The effect of azithromycin on the maturation and function of murine bone marrow derived dendritic cells. AB - Dendritic cells (DCs) are professional antigen-presenting cells capable of initiating primary/adaptive immune responses and tolerance. DC functions are regulated by their state of maturation. However, the molecular pathways leading to DC development and maturation remain poorly understood. We attempted to determine whether inhibition of nuclear factor kappa B (NF-kappaB), which is one of the pivotal pathways underlying these processes, could induce immunophenotypic and functional changes in lipopolysaccharide-induced mature DCs derived from murine bone marrow. A comparative in vitro study of five clinically used drugs that are known to inhibit NF-kappaB demonstrated that azithromycin, a macrolide antibiotic, significantly inhibited expression of co-stimulatory molecules (CD40 and CD86) and major histocompatibility complex (MHC) class II by DCs. It also reduced Toll-like receptor 4 expression, interleukin-12 production and the allostimulatory capacity of DCs. These data suggest that azithromycin, as not only an NF-kappaB inhibitor but also an antibiotic, has potential as a novel drug for manipulation of allogeneic responses. PMID- 22059998 TI - Inequity in work and intimate relationships: a Spillover-Crossover model. AB - This study among 267 Greek teachers and their partners tested and expanded the recently proposed Spillover-Crossover model (SCM) of well-being. Accordingly, experiences built up at work spill over to the home domain, and then influence the partner. The authors integrated equity theory in the model by formulating hypotheses about exchange in interpersonal relationships. Structural equation modeling analyses supported the spillover hypothesis that teachers who lose their work engagement as a result of an inequitable relationship with their students invest less in the relationship with their partner. In addition, the results supported the crossover hypothesis that teachers' relationship investments, in turn, show a negative relationship with inequity in the intimate relationship as perceived by the partner; and inequity in the intimate relationship contributed to partner depression. The findings are discussed in light of the SCM of well being. PMID- 22060000 TI - Electrophilic aromatic sulfonation with SO3: concerted or classic S(E)Ar mechanism? AB - The electrophilic sulfonation of several arenes with SO(3) was examined by electronic structure computations at the M06-2X/6-311+G(2d,2p) and SCS-MP2/6 311+G(2d,2p) levels of theory. In contrast to the usual interpretations, the results provide clear evidence that in nonpolar media and in the absence of catalysts the mechanism of aromatic sulfonation with a single SO(3) is concerted and does not involve the conventionally depicted 1:1 sigma complex (Wheland) intermediate. Moreover, the computed activation energy for the 1:1 process is unrealistically high; barriers for alternative 2:1 mechanisms involving attack by two SO(3) molecules are 12-20 kcal/mol lower! A direct 2:1 sulfonation mechanism, involving a single essential transition state, but no Wheland type intermediate, is preferred generally at MP2 as well as at M06-2X in isolation (gas phase) or in noncomplexing solvents (such as CCl(4) or CFCl(3)). However, in polar, higher dielectric SO(3)-complexing media, M06-2X favors an S(E)Ar mechanism for the 2:1 reaction involving a Wheland-type arene-(SO(3))(2) dimer intermediate. The reaction is slower in complexing solvents, since the association energy, e.g., with nitromethane, must be overcome. But, in accord with the experimental kinetics (second-order in SO(3)), attack by two sulfur trioxide molecules is still favored energetically over reaction with a single SO(3) in CH(3)NO(2). The theoretical results also reproduce the experimental reactivity and regioselectivity trends for benzene, toluene, and naphthalene sulfonation accurately. PMID- 22060001 TI - Improvement of acetazolamide ocular permeation using ascorbyl laurate nanostructures as drug delivery system. AB - PURPOSE: To evaluate the performance of 6-O-Lauryl-l-ascorbic acid nanostructures (coagels) as vehicles for acetazolamide (AZM) in ophthalmic administration by in vitro and in vivo experimental tests. METHODS: The systems of coagel + AZM were evaluated in terms of their in vitro release (dialysis membrane), permeability (isolated cornea), pharmacological effectiveness [intraocular pressure (IOP) reduction in normotensive rabbits], and potential irritant effects. RESULTS: The results concerning AZM permeation were better when vehiculized in coagels compared with ringer solution, which was evident from the AZM steady-state flux and P(app) values (J=1.43 MUg/min and P(app)=3.04 cm.s(1)). As a consequence of this increase in permeation, the coagel-AZMs were more effective in lowering the IOP, according to the results obtained from the in vivo assays. Coagels loaded with 0.4% (W/W) of AZM showed a higher hypotensive effect in rabbits compared with the commercial formulation AZOPT((r)) (brinzolamide 1%), mainly due to the prolonged effect of the former. In all cases, the intensity of irritation was time dependent. The sodium lauryl sulphate solution (2%) used as a positive control produced serious injury 30 min postadministration. This effect caused irritation, which decreased slowly and even at 180 min, the discomfort was still considerable. However, in the case of coagels, a mild-to-moderate effect was observed. CONCLUSIONS: The incorporation of AZM in coagels seems to improve the ocular bioavailability of this drug. Coagel-AZM 0.4% showed a higher hypotensive effect, with a mild-to-moderate irritant effect. These systems could be administrated in human beings, although more detailed studies still need to be carried out. PMID- 22060002 TI - New understanding of memory poses challenges for retrospective research. PMID- 22060003 TI - Understanding the impact of early-life trauma in nursing home residents. AB - Reactions to early life trauma can reemerge or be exacerbated in later life as coping resources and abilities are compromised by age-related changes and declines in health. For newly admitted nursing home residents, this can impact their receptiveness to assistance with care and elicit challenging reactions to environmental and situational triggers. Unfortunately, current assessment tools fail to account for reactions to early-life trauma. In this article, we review existing literature on early-life trauma and aging and introduce a hypothetical case to illustrate the importance of identifying nursing home residents with past trauma experiences. PMID- 22060004 TI - The living-dying interval in nursing home-based end-of-life care: family caregivers' experiences. AB - Guided by concepts from the living-dying interval ( Pattison, 1977 ) this study sought to explore family members' experiences with a dying nursing home resident. In-depth interviews were conducted with 31 caregivers of residents who had died. Interviews were audiotaped and transcribed. Themes that illuminated families' experiences on the living-dying interval were: an acute medical crisis (trigger events, accumulation of stressors, level of care crisis); the living-dying phase (advance care planning, hospitalization, end-stage decisions); and the terminal phase (beginning of the end, awareness of dying). The results illustrate critical periods for social work intervention with families of dying nursing home residents. PMID- 22060005 TI - Health and medical services use: a matched case comparison between CCRC residents and national health and retirement study samples. AB - Little is known about the health status of adults living in continuing care retirement communities (CCRC). Using matched-case control, 458 adults from the Health and Retirement Study (HRS) or a CCRC-based sample were compared on total comorbidity, self-rated health, home health services use, and hospitalizations. At year 2, the CCRC sample reported more comorbidities (96%) but significantly better self-rated health (96% good/excellent) than the HRS sample (93% comorbidity, 73% good/excellent; p < .01). There were no significant differences in frequency of home health use or hospitalization. Living in a CCRC appears to be associated with higher self-ratings of health in this sample. PMID- 22060006 TI - Giving courts the information necessary to implement limited guardianships: are we there yet? AB - A retrospective analysis of written court records and audiotapes of court testimony for adult guardianship cases in 2 Kentucky counties was conducted. Two hundred forty clinical assessments were reviewed for 80 court petitions. The purpose of this research was to learn how interdisciplinary assessment teams contributed to the guardianship process for older adults. Guardianship assessments and court testimony were reviewed to explore the comprehensiveness of reports to the court, the consideration of less restrictive alternatives, and the use of limited guardianships. Recommendations are given for ways in which social workers can improve information given to the courts and advocate for elders in this situation. The role of social work in this national phenomenon is discussed. PMID- 22060007 TI - Welfare reform and elderly immigrants' health insurance coverage: the roles of federal and state medicaid eligibility rules. AB - Immigrants' access to federally-funded Medicaid became limited after welfare reform imposed restrictive noncitizen eligibility rules. This study used a representative sample from the Current Population Survey (N = 105,873) and state level data to examine the effects of these policy changes on elderly immigrants. Triple difference-in-differences analyses show that federal restriction of eligibility had a significantly negative association with elderly immigrants' Medicaid coverage, and generous state eligibility had significantly positive relationships with Medicaid and any health insurance coverage. Findings indicate the important role of eligibility on elderly immigrants' health insurance coverage. Results call for social workers' actions to expand elderly immigrants' Medicaid eligibility. PMID- 22060010 TI - Variation in local institutional review board evaluations of a multicenter patient safety study. AB - Several highly visible quality improvement (QI) projects led to controversy over their ethical oversight, attracting attention from institutional review boards (IRBs) and the Office for Human Research Protection. While QI research has increased dramatically, there is limited empirical evidence regarding how multiple IRBs review the same study. This paper describes the variations in local IRB reviews for the same a multicenter QI study. The study, entitled "Locating Errors through Networked Surveillance", used multiple data collection methods to identify patient safety risks in cardiovascular operating room services. This study involved 2-day site visits to 5 hospitals by the research team to observe cardiac surgery procedures and interview staff regarding clinical practice and hazards. Surveys were self-administered. The IRB process varied widely across the 5 hospitals. Reviews ranged from full committee review and approval with verbal consent required from patients and operating room staff, to an IRB determining the study exempt from review and participant consent. The time to IRB approval ranged from 6 weeks to 6 months. This variation suggests there is wide interpretation of the Federal regulations put in place to guide IRBs. The adoption of uniformity would not only reduce inefficiencies but also attenuate the perceived arbitrary nature of current IRB review processes that often inappropriately influence hypothesis-generation and study design. PMID- 22060011 TI - Neurophysiological investigation of idiopathic acquired auditory-visual synesthesia. AB - We present a case of acquired auditory-visual synesthesia and its neurophysiological investigation in a healthy 42-year-old woman. She started experiencing persistent positive and intermittent negative visual phenomena at age 37 followed by auditory-visual synesthesia. Her neurophysiological investigation included video-EEG, fMRI, and MEG. Auditory stimuli (700 Hz, 50 ms duration, 0.5 s ISI) were presented binaurally at 60 db above the hearing threshold in a dark room. The patient had bilateral symmetrical auditory-evoked neuromagnetic responses followed by an occipital-evoked field 16.3 ms later. The activation of occipital cortex following auditory stimuli may represent recruitment of existing cross-modal sensory pathways. PMID- 22060012 TI - A 48 SNP set for grapevine cultivar identification. AB - BACKGROUND: Rapid and consistent genotyping is an important requirement for cultivar identification in many crop species. Among them grapevine cultivars have been the subject of multiple studies given the large number of synonyms and homonyms generated during many centuries of vegetative multiplication and exchange. Simple sequence repeat (SSR) markers have been preferred until now because of their high level of polymorphism, their codominant nature and their high profile repeatability. However, the rapid application of partial or complete genome sequencing approaches is identifying thousands of single nucleotide polymorphisms (SNP) that can be very useful for such purposes. Although SNP markers are bi-allelic, and therefore not as polymorphic as microsatellites, the high number of loci that can be multiplexed and the possibilities of automation as well as their highly repeatable results under any analytical procedure make them the future markers of choice for any type of genetic identification. RESULTS: We analyzed over 300 SNP in the genome of grapevine using a re sequencing strategy in a selection of 11 genotypes. Among the identified polymorphisms, we selected 48 SNP spread across all grapevine chromosomes with allele frequencies balanced enough as to provide sufficient information content for genetic identification in grapevine allowing for good genotyping success rate. Marker stability was tested in repeated analyses of a selected group of cultivars obtained worldwide to demonstrate their usefulness in genetic identification. CONCLUSIONS: We have selected a set of 48 stable SNP markers with a high discrimination power and a uniform genome distribution (2-3 markers/chromosome), which is proposed as a standard set for grapevine (Vitis vinifera L.) genotyping. Any previous problems derived from microsatellite allele confusion between labs or the need to run reference cultivars to identify allele sizes disappear using this type of marker. Furthermore, because SNP markers are bi-allelic, allele identification and genotype naming are extremely simple and genotypes obtained with different equipments and by different laboratories are always fully comparable. PMID- 22060013 TI - Comparative studies on the crystalline to fluid phase transitions of two equimolar cationic/anionic surfactant mixtures containing dodecylsulfonate and dodecylsulfate. AB - In this work, a cationic surfactant, dodecyltrimethylammonium bromide (DTAB), and an anionic surfactant, sodium dodecylsulfonate (SDSO(3)) or sodium dodecylsulfate (SDSO(4)), were mixed in an equimolar ratio to prepare SDSO(3)-DTAB and SDSO(4) DTAB binary mixtures. The phase behavior, structure, and morphology of these two surfactant mixtures were investigated by differential scanning calorimetry, synchrotron X-ray scattering, freeze-fracture electron microscopy, and Fourier transform infrared spectroscopy. It was found that upon heating, both of the two systems transform from multilamellar crystalline phase to liquid crystalline (or fluid) phase. It is interesting to find that, although SDSO(3) has a lower molecular weight, the crystalline phase of SDSO(3)-DTAB shows much higher thermostability as compared with that of SDSO(4)-DTAB. Other than this, we observed a large difference in the repeat distances of the two crystalline phases. More interestingly, at 60 degrees C in the fluid phases, cylindrical micelles formed in the SDSO(3)-DTAB system, while spherical micelles were observed in the SDSO(4)-DTAB system. Our present work demonstrates that a subtle difference in the headgroup structure of the anionic component markedly affects the thermostability, packing structure, and morphology of the surfactant mixtures, which suggests the importance of the match of the head-head and tail tail interactions between the cationic and anionic surfactants. PMID- 22060014 TI - Reporting of sex as a variable in cardiovascular studies using cultured cells. AB - BACKGROUND: Chromosomal complement, including that provided by the sex chromosomes, influences expression of proteins and molecular signaling in every cell. However, less than 50% of the scientific studies published in 2009 using experimental animals reported sex as a biological variable. Because every cell has a sex, we conducted a literature review to determine the extent to which sex is reported as a variable in cardiovascular studies on cultured cells. METHODS: Articles from 10 cardiovascular journals with high impact factors (Circulation, J Am Coll Cardiol, Eur Heart J, Circ Res, Arterioscler Thromb Vasc Biol, Cardiovasc Res, J Mol Cell Cardiol, Am J Physiol Heart Circ Physiol, J Heart Lung Transplant and J Cardiovasc Pharmacol) and published in 2010 were searched using terms 'cultured' and 'cells' in any order to determine if the sex of those cells was reported. Studies using established cell lines were excluded. RESULTS: Using two separate search strategies, we found that only 25 of 90 articles (28%) and 20 of 101 articles (19.8%) reported the sex of cells. Of those reporting the sex of cells, most (68.9%; n = 31) used only male cells and none used exclusively female cells. In studies reporting the sex of cells of cardiovascular origin, 40% used vascular smooth-muscle cells, and 30% used stem/progenitor cells. In studies using cells of human origin, 35% did not report the sex of those cells. None of the studies using neonatal cardiac myocytes reported the sex of those cells. CONCLUSIONS: The complement of sex chromosomes in cells studied in culture has the potential to affect expression of proteins and 'mechanistic' signaling pathways. Therefore, consistent with scientific excellence, editorial policies should require reporting sex of cells used in in vitro experiments. PMID- 22060015 TI - Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas ligand pathway. AB - BACKGROUND: The lack of effective treatments for gliomas makes them a significant health problem and highlights the need for the development of novel and innovative treatment approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells. However, the absence of well-characterized, highly immunogenic tumor rejection antigens (TRA) in gliomas has limited the implementation of targeted immune-based therapies. METHODS: We hypothesized that treatment with the demethylating agent, decitabine, would upregulate the expression of TRA on tumor cells, thereby facilitating enhanced surveillance by TRA-specific T cells. RESULTS AND DISCUSSION: Treatment of human glioma cells with decitabine increased the expression of NY-ESO-1 and other well characterized cancer testes antigens. The upregulation of NY-ESO-1 made these tumors susceptible to NY-ESO-1-specific T cell recognition and lysis. Interestingly, decitabine treatment of T98 glioma cells also sensitized them to Fas-dependent apoptosis with an agonistic antibody, while a Fas blocking antibody could largely prevent the enhanced functional recognition by NY-ESO-1 specific T cells. Thus, decitabine treatment transformed a non-immunogenic glioma cell into an immunogenic target that was efficiently recognized by NY-ESO-1--specific T cells. CONCLUSIONS: Such data supports the hypothesis that agents which alter epigenetic cellular processes may "immunosensitize" tumor cells to tumor-specific T cell-mediated lysis. PMID- 22060016 TI - A characterization of individual differences in prospective memory monitoring using the Complex Ongoing Serial Task. AB - Prospective memory--remembering to retrieve and execute future goals--is essential to daily life. Prospective remembering is often achieved through effortful monitoring; however, potential individual differences in monitoring patterns have not been characterized. We propose 3 candidate models to characterize the individual differences present in prospective memory monitoring: attentional focus, secondary memory retrieval, and information thresholding. Two experiments using a novel paradigm, the Complex Ongoing Serial Task (COST), investigated the resource allocation patterns underlying individual differences in monitoring. Individuals exhibited differential resource allocation patterns, and the differences remained relatively stable across experimental sessions. Resource allocation patterns associated with information thresholding (high prospective memory, preserved ongoing task performance) and attentional focus (high prospective memory, inefficient ongoing task performance) were superior to secondary memory retrieval (low prospective memory, very inefficient ongoing task performance). Importantly, personality (openness, prevention focus) and cognitive (primary, working, and secondary memory) individual differences influenced monitoring patterns. This research represents the first explicit attempt to elucidate individual differences in prospective memory monitoring patterns. PMID- 22060017 TI - Probing the mechanistic role of the long alpha-helix in subunit L of respiratory Complex I from Escherichia coli by site-directed mutagenesis. AB - The C-terminus of the NuoL subunit of Complex I includes a long amphipathic alpha helix positioned parallel to the membrane, which has been considered to function as a piston in the proton pumping machinery. Here, we have introduced three types of mutations into the nuoL gene to test the piston-like function. First, NuoL was truncated at its C- and N-termini, which resulted in low production of a fragile Complex I with negligible activity. Second, we mutated three partially conserved residues of the amphipathic alpha-helix: Asp and Lys residues and a Pro were substituted for acidic, basic or neutral residues. All these variants exhibited almost a wild-type phenotype. Third, several substitutions and insertions were made to reduce rigidity of the amphipathic alpha-helix, and/or to change its geometry. Most insertions/substitutions resulted in a normal growth phenotype, albeit often with reduced stability of Complex I. In contrast, insertion of six to seven amino acids at a site of the long alpha-helix between NuoL and M resulted in substantial loss of proton pumping efficiency. The implications of these results for the proton pumping mechanism of Complex I are discussed. PMID- 22060018 TI - Catalytic hydroacylation as an approach to homoaldol products. AB - A method has been developed for the intermolecular hydroacylation of homoallyl alcohols with salicylaldehydes to furnish homoaldol products in 50-98% yields. The method also applies to the hydroacylation of 2-hydroxystyrenes. This work highlights the use of hydroacylation as a unified approach to both aldol and homoaldol products. PMID- 22060020 TI - Analysis of mixed micellar behavior of cationic gemini alkanediyl-alpha,omega bis(dimethylcetylammonium bromide) series with ionic and nonionic hydrotropes in aqueous medium at different temperatures. AB - The interaction between cationic symmetrical gemini alkanediyl-alpha,omega bis(dimethylcetylammonium bromide) series (16-s-16, s = 5, 6, abbreviated as G5 and G6) with hydrotropes (cationic: aniline hydrochloride, para-toluidine hydrochloride, and ortho-toluidine hydrochloride; nonionic: phenol, resorcinol, and pyrogallol) in aqueous medium has been investigated at four different temperatures ranging from 298.15 to 313.15 K. Different physicochemical parameters such as critical micelle concentration (cmc), interaction parameter (beta(m), an energetic parameter that represents the excess Gibbs free energy of mixing), activity coefficients (f(i)), mole fraction of hydrotrope in mixed micelles at ideal mixing conditions (X(1)(ideal))(,) excess free energy of mixing (Delta(mix)G(E)), standard enthalpy (Delta(mic)H degrees ), entropy (Delta(mic)S degrees ), and Gibbs free energy (Delta(mic)G degrees ) of micellization were evaluated and then intracompared. For further understanding, similar studies were carried out with their conventional counterpart cetyltrimethyl ammonium bromide (CTAB) and then compared. The bulk behaviors were explored using different theoretical models of Clint, Rubingh, and Motomura for justification and comparison of results of different binary combinations of hydrotropes with the gemini series and CTAB. Synergistic interaction was observed in all binary combinations at all temperatures in the micelles which decreases slightly with increasing temperature. This study will give insight into the selection of surfactants in different applications as their properties get modified by interaction with hydrotropes, thus influencing their solution behavior which, in turn, modifying the phase-forming behavior, microemulsion, liquid crystal forming systems, clouding phenomenon, cleaning, and laundry processes besides solubilization. The ability of hydrotropes to dramatically alter the solubility of other molecules in a medium can be exploited for the purpose of selective encapsulation and release. PMID- 22060019 TI - Nitrate and ammonium lead to distinct global dynamic phosphorylation patterns when resupplied to nitrogen-starved Arabidopsis seedlings. AB - Nitrogen is an essential macronutrient for plant growth and development. Inorganic nitrogen and its assimilation products control various metabolic, physiological and developmental processes. Although the transcriptional responses induced by nitrogen have been extensively studied in the past, our work here focused on the discovery of candidate proteins for regulatory events that are complementary to transcriptional changes. Most signaling pathways involve modulation of protein abundance and/or activity by protein phosphorylation. Therefore, we analyzed the dynamic changes in protein phosphorylation in membrane and soluble proteins from plants exposed to rapid changes in nutrient availability over a time course of 30 min. Plants were starved of nitrogen and subsequently resupplied with nitrogen in the form of nitrate or ammonium. Proteins with maximum change in their phosphorylation level at up to 5 min after nitrogen resupply (fast responses) included GPI-anchored proteins, receptor kinases and transcription factors, while proteins with maximum change in their phosphorylation level after 10 min of nitrogen resupply (late responses) included proteins involved in protein synthesis and degradation, as well as proteins with functions in central metabolism and hormone metabolism. Resupply of nitrogen in the form of nitrate or ammonium resulted in distinct phosphorylation patterns, mainly of proteins with signaling functions, transcription factors and transporters. PMID- 22060021 TI - Investigation of methods to detect mechanically recovered meat in meat products - I: Chemical composition. AB - The proximate composition (fat, moisture, nitrogen, ash and collagen) and the calcium, iron and total purine contents of samples of mechanically recovered meat (MRM) derived from beef, lamb, pork, chicken and turkey were analysed. The data obtained illustrate the variability in the composition of mechanically recovered meats derived from different meat species. The effect of including a high proportion of bones containing marrow in the starting material, the effect of recovery machine type (Yieldmaster and Protecon) and the effect of employing different operating conditions, were investigated. MRM produced using the Yieldmaster machine was generally found to contain higher concentrations of ash and calcium than that produced using the Protecon machine. Although operating conditions appeared to have little effect on the composition of mechanically recovered chicken meat, some differences were identified in mechanically recovered turkey and pork produced under different conditions. Comparison of the composition of MRM with that of meat removed manually, from close to the bone, from similar source materials highlighted a number of differences between the. PMID- 22060022 TI - Investigation of methods to detect mechanically recovered meat in meat products - II: Gel electrophoresis. AB - This study investigated the use of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) as a method for differentiating between mechanically recovered and hand deboned meat. Twenty-nine samples of mechanically recovered meat (MRM), including some heat treated samples, were obtained. The samples were derived from several animal species and processed using different machine types and a range of processing conditions. They were examined using SDS-PAGE and the separation patterns obtained compared with those of hand deboned meat (HDM) reference samples. There were obvious differences in the relative intensities of several bands within the profiles obtained which distinguished MRM from HDM. These were more obvious for red meat than poultry meat samples. A few differences were found between MRM samples produced using different machines but no apparent differences between samples produced using different machine operating conditions were observed. The technique was tested using composite MRM-HDM mixtures. It was possible to suggest an order of percentage incorporation of MRM at levels of down to 5-10% for red meat and 25% for poultry meat. With further development and refinement, it may be possible to use the technique to detect and possibly quantify MRM present in all types of meat products, including cooked meat products. PMID- 22060023 TI - Investigation of methods to detect mechanically recovered meat in meat products - III: Microscopy. AB - This was a preliminary study to investigate whether hyaline cartilage could be easily identified in mechanically recovered meat (MRM) and whether its presence could be used as a possible marker for MRM in meat products. MRMs produced from beef, pork, lamb, chicken and turkey, using a variety of machine types and processing conditions, were compared to both minced and colloid milled hand deboned samples, using a chemical staining technique followed by examination using the light microscope. The methodology was tested on various mixtures of MRM and hand-deboned meat. Although this technique, as with most microscopy techniques generally, is not suitable for quantitative determinations, the results indicate that light microscopy could be used as a useful screening method. PMID- 22060024 TI - Investigation of methods to detect mechanically recovered meat in meat products - IV: Immunology. AB - The possibility of using immunological techniques as a method for the detection of mechanically recovered chicken meat in meat products has been investigated in this preliminary study. Antibodies were raised against a low molecular weight fraction (<= 30 kDa) of chicken bone marrow proteins and an enzyme-linked immunosorbent assay (ELISA) developed. The system was used to test for the presence of mechanically recovered meat (MRM) in a range of product types, from raw chicken meat through to heat processed samples. The results show that it is possible to raise antibodies to chicken bone marrow proteins which show a strong reactivity with chicken and turkey MRM but show little reaction with extracts of MRM and hand deboned meat of other common meat species. However, blood, skin and soya all affected the accuracy of the ELISA. This study has demonstrated the potential for the use of an immunological procedure as a rapid test for MRM. The selectivity of the antiserum would, however, have to be increased before this procedure could be considered as a suitable technique for the detection of MRM in meat products. PMID- 22060025 TI - Effects of dietary clenbuterol and salbutamol on meat quality in veal calves. AB - Sixty male calves were assigned to one of four treatments, including (1) an untreated control, (2) clenbuterol; 1.6 mg/(calf.day), (3) and (4) salbutamol: 60 and 100 mg/(calf.day). Animals were milk-fed during 24 weeks, and beta(2) agonists (BA) treatment occurred during the last 4 weeks including a 3-day withdrawal period before slaughter. Under identical feed intake amongst groups, treatments with BA had significantly positive effects on carcass weights and dressing percentages. BA induced muscle hypertrophy as evidenced by an improved EUROP carcass classification, 1 19-24% higher m. longissimus loin eye area and higher muscle protein/DNA and protein/RNA ratios. Through a dilution effect, this might explain the lower haem content of the m. semimembranosus and m. longissimus lumborum (LL) and diminished Hunter a(*) value (redness) of the latter muscle. A higher ultimate pH was found in the m. semitendinosus and m. psoas major of BA treated calves. The m. longissimus thoracis glycogen content appeared to be lowered by salbutamol. No effects of BA were encountered for water-holding properties of this muscle. Significantly higher shear force values (31-45%) for treated animals were measured for the LL which were parallelled by higher initial values for the calpain-inhibiting activity of calpastatin and a decrease of the MU-calpain/calpastatin ratio. EUROP fatness of carcasses and LL intramuscular fat content tended to be lowered by both BA. Effects of clenbuterol and of the higher salbutamol dose, which on a molecular base was administered at a 70 times higher level, were roughly of a comparable order. The lower dose mostly had intermediate effects. This means that in veal calves, clenbuterol is biologically more potent than salbutamol. PMID- 22060026 TI - Effect of the addition of pancreatic lipase on the ripening of dry-fermented sausages - Part 2. Free fatty acids, short-chain fatty acids, carbonyls and sensory quality. AB - The effect of the addition of nine different amounts (3-500 units) of pancreatic lipase on the composition of free fatty acids (FFA), short-chain fatty acids and carbonyls, as well as the sensory quality, has been studied on dry fermented sausages. The lipase produced a greater release of all fatty acids in relation to the control sausages. The greater the pancreatic lipase content, the higher the release of these fatty acids, the most important ones being myristic, palmitoleic and oleic acids. A lower release of linoleic acid was observed, probably because of its oxidative degradation. At the end of the ripening in all lipase-added batches, a clear increase of the carbonyl content was noticed in relation to conventional sausages. No consistent changes were observed in the short-chain fatty acid fraction. In the sensory evaluation, the highest significant differences (P < 0.01) between control sausages and lipase-added batches were observed when 60 and 90 lipase units were used. According to the chemical and sensory analyses, it can be concluded that the addition of 60 and 90 units to sausages seems to be useful to enhanced the flavour of these products. PMID- 22060027 TI - Sensory evaluation of beef patties and sausages containing lipids with various component fatty acids. AB - Sensory scores of beef patties and emulsion-type sausages containing varying levels of lipids with various component fatty acids were investigated. Sensory scores of beef patties containing solid fat were relatively constant at every fat level examined. However, scores of beef patties containing liquid oil decreased with increasing level of added oil. In the case of sausages, on the other hand, sensory evaluation scores markedly decreased with increasing the level of solid fat, while no significant change was observed in panel scores when liquid oil was mixed into sausages. Even 10% level of added lipids satisfactorily gave preferable acceptability to beef patties and sausages. PMID- 22060028 TI - Variability within intramuscular fat content of pigs as measured by gravimetry, FTIR and NMR spectroscopy. AB - In order to determine in vivo intramuscular fat content of pigs' biceps femoris, three methods were compared. Gravimetry and FTIR spectroscopy after total fat extraction from a biopsy (about 400 mg skeletal muscle tissue) and in vivo (1)H NMR spectroscopy after imaging and volume of interest selection were used. Mean values (g fat/100 g fresh tissue) were, respectively, 1.47 +/- 0.35 (gravimetry), 1.26 +/- 0.33 (FTIR) and 0.51 +/- 0.19 (NMR); but NMR-values represented only triglycerides. Within an intramuscular fat range from 1.1 to 2.7 g per 100 g fresh muscle tissue, possible to estimate a calibration line between the in vitro and in vivo data for hybrid piglets of about 18 kg. Repeated in vivo NMR measurements on the same muscle volume showed a mean coefficient of variation of 5.5 +/- 2.7%. The coefficient of variation of measurements on different volumes within the same muscle was 14 +/- 10%. The mean intramuscular fat content of 18 kg or 100 kg pigs was, respectively, 1.64 +/- 0.46 (biceps femoris) and 1.32 +/- 0.1 (longissimus dorsi) g per 100 g fresh muscle tissue. PMID- 22060029 TI - Microbial and chemical changes in 'Sobrasada' during ripening. AB - 'Sobrasada' is a raw-cured product typical of Mallorca (Balearic Islands). Throughout its ripening process the product, like other raw-cured sausages, undergoes a series of chemical and microbial changes which lead to the formation of its desirable final characteristics. In the 'sobrasada' studied, the breeds, feeding and casings used in the Balearic Islands were employed. The evolution of different groups of microorganisms was followed: mesophylic aerobic microorganisms, lactic acid bacteria, Enterobacteriaceae, yeasts and moulds, group D Streptococcus, proteolytic microorganisms and lipolytic microorganisms. It was found that the predominant flora, from the beginning to the end, was made up of lactic acid bacteria. Conversely, Enterobacteriaceae disappeared as ripening went on, and the rest of the microbial groups studied underwent little variation along the process. An important characteristics of the product is the fast fall of pH, from values near 6.0 to values around 5.3, in the first week. PMID- 22060030 TI - Biochemical changes in an intermediate moisture cecina-like meat during storage. AB - Biochemical and microbiological changes in two cecina-like products were evaluated during storage. Two products were prepared, one by salting and the other by infusion in a salt-glycerol solution. The samples were vacuum packed and tested monthly for pH, colour, haematin complex, soluble nitrogen and microbiological spoilage. Proteolysis and increase in pH showed a high correlation for both samples. Temperature-dependent changes in colour and concentration of haematin complex during storage were also found in both samples. The activation energy for haematin transformation was found to be around 1 kcal/mol. Based on the low activation energy for haematin complex degradation (around 1 kcal/mol) for both samples, this process may be regarded as a low energy biochemical process. PMID- 22060031 TI - Inoculation of lactic acid bacteria on meat surfaces as a means of decontamination in semitropical conditions. AB - Reduction of microbial populations on carcasses has been achieved and reported by some authors by spraying solutions of organic acids, mainly lactic acid, on the meat surface. However, in practice, lactic acid is very expensive. Production of lactic acid in situ by a controlled lactic fermentation seemed to be a feasible answer. The objective of the present study was to explore the viability of this concept at semitropical conditions, i.e. temperatures around 25 degrees C. In a first experiment, seven starters were tested for their ability to produce lactic acid and reducing the growth rate of pseudomonads, taking these microorganisms as indicators of contamination by spoilage microorganisms. The lactic acid bacteria strains were isolated from native Mexican maize-based beverages, and inoculated on the meat surface. Addition of sucrose and wrapping the samples in PVC film in order to induce a microaerophilic environment encouraged the over-growth of L. bulgaricus and P. pentosaceous over pseudomonads. A second experiment was designed to test a mixture of these two strains and a commercial starter with respect to lactic acid production, overgrowth of lactic acid bacteria over pseudomonads, decolouration and oxidation of the meat samples. It was concluded that a commercial starter (L. plantarum + M. kristinae-varians) resulted in a reduction of pseudomonas growth rate, without notably affecting meat colour and degree of oxidation. PMID- 22060032 TI - Relationship between the translocation of paratropomyosin and the restoration of rigor-shortened sarcomeres during post-mortem ageing of meat-A molecular mechanism of meat tenderization. AB - The weakening effect of paratropomyosin on rigor linkages formed between actin and myosin was determined by measuring the restoration of rigor-shortened sarcomeres of chicken, pork and beef. We observed the rate of the post-mortem translocation of paratropomyosin from the A-I junction region of sarcomeres onto the thin filaments in the A-band, where rigor linkages had been formed; this agreed well with the rate of increase in length of rigor-shortened sarcomeres. The sarcomere lengths were found to be maximum at 1, 7 and 10 days post-mortem in chicken, pork and beef, respectively. Thus, translocated paratropomyosin weakens rigor linkages and brings about the recovery in the length of rigor-shortened sarcomeres. Paratropomyosin stimulates the resolution of rigor mortis, and is a key factor in meat tenderization during post-rigor ageing. These results powerfully support the 'Calcium theory of meat tenderization' which we have proposed. PMID- 22060033 TI - 5-Amino-2-aroylquinolines as highly potent tubulin polymerization inhibitors. Part 2. The impact of bridging groups at position C-2. AB - A variety of studies on the modification of combretastatin A-4 triggered our interest in the impact of the linkers between the 3,4,5-trimethoxyphenyl ring and 5-amino-6-methoxyquinoline on biological activity. The replacement of the carbonyl group with bond, amine, ether, sulfide, and sulfone groups was evaluated in this study. The results showed that compounds 14 and 15 containing sulfide and sulfone groups between the 3,4,5-trimethoxyphenyl ring (A-ring) and 5-amino-6 methoxyquinoline exhibited substantial antiproliferative activity against KB, HT29, and MKN45 cells with mean IC50 values of 42 and 12 nM, respectively. 15 inhibited the tubulin polymerization with an IC50 value of 2.0 MUM, similar to that with CA4. The continued work on the C-5 substituents of 3',4',5' trimethoxybenzoyl-6-methoxyquinoline derivatives demonstrated that compound 7 possessing OH at C-5 exhibited excellent antiproliferative activity with mean IC50 values of 3.4 nM and microtubule destabilizing potency with an IC50 of 1.5 MUM, comparable to that of CA4 (IC50=1.9 MUM). It also exhibited substantial vascular disrupting effects. Compounds 7 and 15 exhibited significant efficacy against MDR/MRP-related drug-resistant cell lines (KB-vin10, KB-S15, and KB-7D) with mean IC50 values of 6.7 and 2.6 nM, respectively. PMID- 22060034 TI - The key to enabling biosurveillance is cooperative technology development. AB - The world population will continue to face biological threats, whether they are naturally occurring or intentional events. The speed with which diseases can emerge and spread presents serious challenges, because the impact on public health, the economy, and development can be huge. The U.S. government recognizes that global public health can also have an impact on national security. This global perspective manifests itself in U.S. policy documents that clearly articulate the importance of biosurveillance in providing early warning, detection, and situational awareness of infectious disease threats in order to mount a rapid response and save lives. In this commentary, we suggest that early recognition of infectious disease threats, whether naturally occurring or man made, requires a globally distributed array of interoperable hardware and software fielded in sufficient numbers to create a network of linked collection nodes. We argue that achievement of this end state will require a degree of cooperation that does not exist at this time-either across the U.S. federal government or among our global partners. Successful fielding of a family of interoperable technologies will require interagency research, development, and purchase ("acquisition") of biosurveillance systems through cooperative ventures that likely will involve our strategic allies and public-private partnerships. To this end, we propose leveraging an existing federal interagency group to integrate the acquisition of technologies to enable global biosurveillance. PMID- 22060035 TI - The Civil Air Patrol's role in medical countermeasure distribution in Michigan. AB - Michigan's unique geological features and highly variable climatic conditions make distribution of medical countermeasures during a public health emergency situation very challenging. To enhance distribution during these situations, the Civil Air Patrol (CAP) has agreed to support the state of Michigan by transporting life-saving medical countermeasures to remote areas of the state. The Michigan Strategic National Stockpile (MISNS) program has successfully developed, exercised, and enhanced its partnership with the CAP to include distribution of federally provided Strategic National Stockpile (SNS) assets. The CAP has proven to be a reliable and valuable partner, as well as a cost-effective and time-efficient means of transporting vital resources during a public health emergency. PMID- 22060036 TI - Unfinished business: efforts to define dual-use research of bioterrorism concern. AB - Biotechnological research poses a special security problem because of the duality between beneficial use and misuse. In order to find a balance between regulating potentially dangerous research and assuring scientific advancement, a number of assessments have tried to define which types of research are especially open to misuse and should therefore be considered dual-use research of special concern requiring rigorous oversight. So far, there has been no common understanding of what such activities are. Here we present a review of 27 assessments focusing on biological dual-use issues published between 1997 and 2008. Dual-use research activities identified by these assessments as being of special concern were compiled and compared. Moreover, from these 27 assessments, the primary research publications explicitly identified as examples of concerning research activities were extracted and analyzed. We extracted a core list of 11 activities of special concern and show that this list does not match with the reasons why primary research publications were identified as being of special concern. Additionally, we note that the 11 activities identified are not easily conducted or replicated, and therefore the likelihood of their being used in a high-tech mass casualty bioterrorism event should be reevaluated. PMID- 22060037 TI - Interferometric methods for label-free molecular interaction studies. PMID- 22060038 TI - Charge modifications to improve the emulsifying properties of whey protein isolate. AB - Whey protein isolate was modified by ethylene diamine in order to shift its isoelectric point to an alkaline pH. The extent of the modification was studied using SDS-PAGE and MALDI-TOF mass spectrometry. The modified whey proteins were used as an emulsifier to stabilize oil-in-water emulsions at acidic and neutral pH ranges, and their emulsifying properties were compared with that of the unmodified whey proteins and with the previously studied ethylene diamine modified sodium caseinate. The emulsifying activity of the modified whey proteins was similar to that of the unmodified ones, but the stability of an emulsion at pH 5 was significantly improved after the modification. Charge and coverage of droplet surface and the displacement of the interfacial proteins by surfactant Tween 20 were further studied as a function of pH. As compared with the unmodified whey proteins, the modified ones were proven to cover the interface more efficiently with extensive surface charge at pH 5, although the interfacial layer was less resistant to the surfactant displacement. PMID- 22060039 TI - Renal function after tandem high-dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor. AB - Despite increasing evidence that tandem HDCT and autoSCT might improve the survival of patients with high-risk solid tumors, patients with Wilms tumor may be at high risk of acute and chronic renal impairment during and after tandem HDCT/autoSCT because they usually have a single kidney. We investigated the feasibility of tandem HDCT/autoSCT in patients with Wilms tumor, focusing on renal function. Six patients with relapsed/progressed Wilms tumor were assigned to undergo tandem HDCT/autoSCT. One patient developed transient ARF during the first HDCT/autoSCT. All other patients underwent the second HDCT/autoSCT as scheduled. Acute renal dysfunction during the second HDCT/autoSCT was transient and manageable. Indicators of glomerular function such as creatinine clearance, serum creatinine, and albumin excretion were in the normal range at three yr after tandem HDCT/autoSCT. Subclinical tubular dysfunctions, such as increased excretion of beta-N-acetylglucosaminidase and beta2-microglobulin, were identified at one and three yr after tandem HDCT/autoSCT; however, no patient required treatment for these conditions. These results are helpful to consider tandem HDCT/autoSCT as a treatment option in patients with Wilms tumor. Longer duration of follow-up and close monitoring of tubular function are required if tandem HDCT/autoSCT is indicated in patients with Wilms tumor. PMID- 22060040 TI - Genetics and control of tomato fruit ripening and quality attributes. AB - Tomato ripening is a highly coordinated developmental process that coincides with seed maturation. Regulated expression of thousands of genes controls fruit softening as well as accumulation of pigments, sugars, acids, and volatile compounds that increase attraction to animals. A combination of molecular tools and ripening-affected mutants has permitted researchers to establish a framework for the control of ripening. Tomato is a climacteric fruit, with an absolute requirement for the phytohormone ethylene to ripen. This dependence upon ethylene has established tomato fruit ripening as a model system for study of regulation of its synthesis and perception. In addition, several important ripening mutants, including rin, nor, and Cnr, have provided novel insights into the control of ripening processes. Here, we describe how ethylene and the transcription factors associated with the ripening process fit together into a network controlling ripening. PMID- 22060041 TI - Toxin-antitoxin systems in bacteria and archaea. AB - Almost all bacteria and many archaea contain genes whose expression inhibits cell growth and may lead to cell death when overproduced, reminiscent of apoptotic genes in higher systems. The cellular targets of these toxins are quite diverse and include DNA replication, mRNA stability, protein synthesis, cell-wall biosynthesis, and ATP synthesis. These toxins are co-expressed and neutralized with their cognate antitoxins from a TA (toxin-antitoxin) operon in normally growing cells. Antitoxins are more labile than toxins and are readily degraded under stress conditions, allowing the toxins to exert their toxic effect. Presence of at least 33 TA systems in Escherichia coli and more than 60 TA systems in Mycobacterium tuberculosis suggests that the TA systems are involved not only in normal bacterial physiology but also in pathogenicity of bacteria. The elucidation of their cellular function and regulation is thus crucial for our understanding of bacterial physiology under various stress conditions. PMID- 22060042 TI - A genetic approach to the transcriptional regulation of Hox gene clusters. AB - The evolution of vertebrate genomes was accompanied by an astounding increase in the complexity of their regulatory modalities. Genetic redundancy resulting from large-scale genome duplications at the base of the chordate tree was repeatedly exploited by the functional redeployment of paralogous genes via innovations in their regulatory circuits. As a paradigm of such regulatory evolution, we have extensively studied those control mechanisms at work in-cis over vertebrate Hox gene clusters. Here, we review the portfolio of genetic strategies that have been developed to tackle the intricate relationship between genomic topography and the transcriptional activities in this gene family, and we describe some of the mechanistic insights we gained by using the HoxD cluster as an example. We discuss the high heuristic value of this system in our general understanding of how changes in transcriptional regulation can diversify gene function and thereby fuel morphological evolution. PMID- 22060043 TI - CRISPR-Cas systems in bacteria and archaea: versatile small RNAs for adaptive defense and regulation. AB - Bacteria and archaea have evolved defense and regulatory mechanisms to cope with various environmental stressors, including virus attack. This arsenal has been expanded by the recent discovery of the versatile CRISPR-Cas system, which has two novel features. First, the host can specifically incorporate short sequences from invading genetic elements (virus or plasmid) into a region of its genome that is distinguished by clustered regularly interspaced short palindromic repeats (CRISPRs). Second, when these sequences are transcribed and precisely processed into small RNAs, they guide a multifunctional protein complex (Cas proteins) to recognize and cleave incoming foreign genetic material. This adaptive immunity system, which uses a library of small noncoding RNAs as a potent weapon against fast-evolving viruses, is also used as a regulatory system by the host. Exciting breakthroughs in understanding the mechanisms of the CRISPR Cas system and its potential for biotechnological applications and understanding evolutionary dynamics are discussed. PMID- 22060045 TI - Formation mechanism and structure of a guanine-uracil DNA intrastrand cross-link. AB - The formation and structure of the 5'-G[8-5]U-3' intrastrand cross-link are studied using density functional theory and molecular dynamics simulations due to the potential role of this lesion in the activity of 5-halouracils in antitumor therapies. Upon UV irradiation of 5-halouracil-containing DNA, a guanine radical cation reacts with the uracil radical to form the cross-link, which involves phosphorescence or an intersystem crossing and a rate-determining step of bond formation. Following ionizing radiation, guanine and the uracil radical react, with a rate-limiting step involving hydrogen atom removal. Although cross-link formation from UV radiation is favored, comparison of calculated reaction thermokinetics with that for related experimentally observed purine-pyrimidine cross-links suggests this lesion is also likely to form from ionizing radiation. For the first time, the structure of 5'-G[8-5]U-3' within DNA is identified by molecular dynamics simulations. Furthermore, three conformations of cross-linked DNA are revealed, which differ in the configuration of the complementary bases. Distortions, such as unwinding, are localized to the cross-linked dinucleotide and complementary nucleotides, with minimal changes to the flanking bases. Global changes to the helix, such as bending and groove alterations, parallel cisplatin induced distortions, which indicate 5'-G[8-5]U-3', may contribute to the cytotoxicity of halouracils in tumor cell DNA using similar mechanisms. PMID- 22060046 TI - Clinical and microbiologic evaluation, by real-time polymerase chain reaction, of non-surgical treatment of aggressive periodontitis associated with amoxicillin and metronidazole. AB - BACKGROUND: The aim of the present study is to evaluate the clinical and microbiologic changes resulting from non-surgical periodontal treatment associated with amoxicillin and metronidazole in individuals with aggressive periodontitis. METHODS: Fifteen individuals with aggressive periodontitis received non-surgical periodontal treatment and 45 days after completion of treatment were treated with antibiotics. Clinical data and samples of subgingival plaque were collected at baseline, 45 days after the non-surgical periodontal treatment, and 1 month after the use of antimicrobial agents. After 3 and 6 months, only clinical data were collected. The presence and quantification of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), and Dialister pneumosintes were determined by real-time polymerase chain reaction. RESULTS: All clinical parameters, with the exception of clinical attachment level (CAL), had significantly (P <0.05) improved at the end of the third month after non-surgical therapy associated with antibiotics. There was significant (P <0.05) reduction in the quantities of Td and Tf. After 1 month, there were significant (P <0.05) reductions in the frequencies of Pg and Tf. CONCLUSION: Non-surgical mechanical treatment associated with the use of amoxicillin and metronidazole led to an improvement in all clinical parameters studied, except for CAL, and significantly reduced the amount of subgingival Tf and Td. PMID- 22060047 TI - Radiographic periodontal bone loss in chronic kidney disease. AB - BACKGROUND: We examined the extent and severity of radiographic periodontal bone loss in patients with different stages of chronic kidney disease (CKD) and explored a potential dose-response relationship between bone loss and CKD-related biomarkers. METHODS: Panoramic radiographs were obtained from 129 CKD patients (78 males and 51 females; mean age: 63.5 years, range: 24 to 91 years), including 63 patients undergoing dialysis for an average of 3.3 years (range: 0.5 to 14 years). Glomerular filtration rate (GFR), dialysis dose, and levels of serum biomarkers were obtained through a hospital database. Interproximal bone loss was assessed as a percentage of root length. RESULTS: Twenty-nine participants were edentulous (23.8% of those on dialysis versus 21.2% of those with residual kidney function; chi(2) test, P = 0.724). The extent of bone loss was higher among dialysis patients (analysis of variance [ANOVA], P = 0.007), but no clear dose response association between CKD stage and extent was evident. GFR, dialysis dose, and levels of serum biomarkers did not differ between edentulous and dentate individuals, and only serum albumin was lower in patients with extensive bone loss (ANOVA, P = 0.030). After adjusting for dialysis status, the severity of bone loss was positively associated with glucose levels (multiple regression, P = 0.019) and white blood cell count (P = 0.032), whereas the number of teeth present was positively associated with plasma phosphorus (P = 0.008) and negatively with glucose levels (P = 0.011). CONCLUSION: Despite a higher extent of bone loss in dialysis patients, the lack of a dose-response association between bone loss and CKD stage or the levels of CKD-related serum biomarkers underscores the complex relationship between the two conditions. PMID- 22060048 TI - Effect of maxillary sinus floor augmentation on sinus membrane thickness in computed tomography. AB - BACKGROUND: Little is known about maxillary sinus compliance, i.e., the intrinsic potential of the sinus membrane to resume its homeostatic status after the surgical trauma caused by sinus floor elevation. The aim of the present study is to investigate the effect of maxillary sinus floor augmentation on sinus membrane thickness. METHODS: Within-patient comparison of computed tomographic scans before bone grafting versus 4 to 6 months after bone grafting was performed. Changes in membrane thickness were evaluated in 65 maxillary sinus floor augmentation procedures via a lateral approach in 35 patients without clinical signs of sinus pathology at any time. RESULTS: Sinus membrane thickness differed significantly before (0.8 +/- 1.2 mm) versus after (1.5 +/- 1.3 mm) augmentation surgery (P <0.001), with a mean increase of 0.8 +/- 1.6 mm (maximum: 4.4 mm). Only 28% of augmented sinuses did not show membrane thickening. In non-augmented control sinuses, there was no evidence of membrane thickness increase. CONCLUSIONS: The results indicate that the maxillary sinus membrane, even in healthy clinical conditions, undergoes morphologic modifications after sinus floor elevation, yet membrane reactions demonstrate significant variability. Future research on the effect of augmentation surgery on maxillary sinus physiology is recommended. PMID- 22060049 TI - Measurement of atherosclerosis markers in patients with periodontitis: a case control study. AB - BACKGROUND: It is suggested that periodontitis enhances the process of vascular inflammation leading to atherosclerosis. The present study explores the effect of periodontitis in relation to the clinical and ultrasound markers of carotid atherosclerosis. METHODS: Sixty systemically healthy patients >45 years of age (30 with chronic periodontitis and 30 without periodontitis) were studied in a university dental school. Traditional cardiovascular risk factors for atherosclerosis were evaluated. Carotid intima-media thickness (IMT) was assessed by ultrasound. RESULTS: The internal carotid IMT was 0.77 and 0.81 mm in the periodontal disease and control groups, respectively, with no statistically significant differences between the two groups (P = 0.538). There were significant differences in the presence of carotid atheroma plaques and the severity of periodontitis (P = 0.003). In the logistic regression analysis, significant differences in terms of age and periodontitis were recorded in relation to the presence of atheroma plaques in the carotid intima. CONCLUSION: The severity of periodontitis was seen to influence the presence of carotid atheroma plaques. PMID- 22060050 TI - Periosteal distraction osteogenesis and barrier membrane application: an experimental study in the rat calvaria. AB - BACKGROUND: Distraction of the periosteum results in the formation of new bone in the gap between the periosteum and the original bone. We postulate that the use of a barrier membrane would be beneficial for new bone formation in periosteal distraction. METHODS: To selectively influence the contribution of the periosteum, a distraction plate with perforations was used alone or covered by a collagen barrier membrane. All animals were subjected to a 7-day latency period and a 10-day distraction period with a rate of 0.1 mm/day. Four animals per group with or without a barrier membrane were sacrificed at 2, 4, and 6 weeks after the end of the distraction. The height of new bone generated relative to the areas bound by the parent bone and the periosteum was determined by histomorphometric methods. RESULTS: New bone was found in all groups. At the periphery of the distraction plate, significant differences in bone height were found between the hinge and the distraction screw for the group without barrier membrane at 2 weeks (0.39 +/- 0.19 mm) compared to 4 weeks (0.84 +/- 0.44 mm; P = 0.002) and 6 weeks (1.06 +/- 0.39 mm; P = 0.004). Differences in maximum bone height with and without a barrier membrane were observed laterally to the distraction plate at 2 weeks (1.22 +/- 0.64 versus 0.55 +/- 0.14 mm; P = 0.019) and 6 weeks (1.61 +/- 0.56 versus 0.73 +/- 0.33 mm; P = 0.003) of the consolidation period. CONCLUSION: Within the limitations of the present study, the application of a barrier membrane may be considered beneficial for new bone formation induced by periosteal distraction. PMID- 22060052 TI - Age standardization in mapping adult overweight and obesity trends in the WHO European Region. AB - This study aims to improve comparability of available data within the World Health Organization (WHO) European Region taking into account differences related to the aging of the population. Surveys were included if they were conducted on adults aged 25-64 years between 1985 and 2010 in the WHO European Region. Overweight/obesity prevalences were adjusted to the European standard population aged 25-64. Data were entered for each of the 5-year categories between 1981 and 2010. Measured height and weight data were available for males in 16 and females in 24 of the 53 countries. The 50-64-year-olds had higher prevalence of overweight and obesity as compared to the 25-49-year-olds. This pattern occurs in every country, by male and female, in almost all surveys. Age-standardized overweight prevalence was higher among males than females in all countries. Trend data showed increases in most countries. Age-standardized maps were based on self reported data because of insufficient availability of measured data. Results showed more countries with available data as well as the higher category of obesity in the later surveys. Measured values are needed and age adjustment is important in documenting emerging overweight and obesity trends, independent of demographic changes, in the WHO European Region. PMID- 22060053 TI - Renal differentiation of amniotic fluid stem cells: perspectives for clinical application and for studies on specific human genetic diseases. AB - BACKGROUND: Owing to growing rates of diabetes, hypertension and the ageing population, the prevalence of end-stage renal disease, developed from earlier stages of chronic kidney disease, and of acute renal failure is dramatically increasing. Dialysis and preferable renal transplantation are widely applied therapies for this incurable condition. However these options are limited because of morbidity, shortage of compatible organs and costs. Therefore, stem cell-based approaches are becoming increasingly accepted as an alternative therapeutic strategy. DESIGN: This review summarizes the current findings on the nephrogenic potential of amniotic fluid stem (AFS) cells and their putative implications for clinical applications and for studies on specific human genetic diseases. RESULTS: Since their discovery in 2003, AFS cells have been shown to be pluripotent with the potential to form embryoid bodies. Compared to adult stem cells, induced pluripotent stem cells or embryonic stem cells, AFS cells harbour a variety of advantages, such as their high differentiation and proliferative potential, no need for ectopic induction of pluripotency and no somatic mutations and epigenetic memory of source cells, and no tumourigenic potential and associated ethical controversies, respectively. CONCLUSIONS: Recently, the results of different independent studies provided evidence that AFS cells could indeed be a powerful tool for renal regenerative medicine. PMID- 22060054 TI - NSW immunisation performance: continuing progress but no room for complacency. PMID- 22060055 TI - NSW annual vaccine-preventable disease report, 2010. AB - AIMS: To describe trends in case notification data for vaccine-preventable diseases in NSW for 2010. METHODS: Risk factor and vaccination status data were collected from cases through public health unit follow-up. Data from the NSW Notifiable Conditions Information Management System (NCIMS) were analysed by: local health district of residence; age; vaccination status; and sub-organism, where available. RESULTS: Outbreaks of measles and pertussis were notified in 2010, associated with unimmunised groups (measles) or as a result of waning immunity (pertussis). CONCLUSION: With the exception of pertussis, most vaccine preventable disease notifications remain low in NSW. Ensuring high levels of vaccination for travellers is important to prevent future outbreaks of vaccine preventable disease, particularly measles. PMID- 22060056 TI - NSW annual immunisation coverage report, 2010. AB - This annual report, the second in the series, documents trends in immunisation coverage in NSW for children, adolescents and the elderly, to the end of 2010. METHODS: Data from the Australian Childhood Immunisation Register, the NSW School Immunisation Program and the NSW Population Health Survey were used to calculate various measures of population coverage, coverage for Aboriginal children and vaccination timeliness for all children. RESULTS: Over 90% coverage has been reached for children at 12 and 24 months of age. For children at 5 years of age there was an improvement during 2010 in timeliness for vaccines due at 4 years and coverage almost reached 90%. Delayed receipt of vaccines is still an issue for Aboriginal children. For adolescents, there is good coverage for the first and second doses of human papillomavirus vaccine and the dose of diphtheria, tetanus and acellular pertussis. The pneumococcal vaccination rate in the elderly has been steadily rising, although it has remained lower than the influenza coverage estimates. CONCLUSION: Completion of the recommended immunisation schedule at the earliest appropriate age should be the next public health goal at both the state and local health district level. Official coverage assessments for 'fully immunised' should include the 7-valent pneumococcal conjugate and meningococcal C vaccines, and wider dissemination should be considered. PMID- 22060057 TI - NSW annual report describing adverse events following immunisation, 2010. AB - AIM: This report summarises Australian passive surveillance data for adverse events following immunisation in NSW for 2010. METHODS: Analysis of de-identified information on all adverse events following immunisation reported to the Therapeutic Goods Administration. RESULTS: 424 adverse events following immunisation were reported for vaccines administered in 2010; this is 6% lower than 2009 but 24% higher than 2008 and the second highest number since 2003. A total of 274 (65%) adverse events involved seasonal or pandemic influenza vaccines. Reports were predominantly of mild transient events: the most commonly reported reactions were fever, allergic reaction, injection site reaction, malaise and headache. Only 9% of the reported adverse events were serious in nature, including eight reports of febrile convulsions in children following seasonal influenza vaccine. CONCLUSION: The large number of reports in 2010 is attributable to the high rates of fever and febrile convulsions in children after vaccination with 2010 seasonal trivalent influenza vaccine, as well as pandemic (H1N1) 2009 influenza vaccine. PMID- 22060059 TI - Bug breakfast in the bulletin: trachoma. PMID- 22060060 TI - Communicable Diseases Report, NSW, July and August 2011. PMID- 22060061 TI - Implementation of routine rapid HIV testing within the U.S. Department of Veterans Affairs Healthcare System. AB - Current HIV testing methods can be ineffective; patients often do not return for results. HIV rapid testing (RT) provides accurate results in 20 min. Patients find nurse-initiated HIV rapid testing (NRT) more acceptable than current testing methods and increases receipt of test results. Translating research findings into sustainable practice poses widely recognized implementation challenges. To ascertain effectiveness of NRT implementation, formative and process evaluations were conducted within the U.S. Department of Veterans Affairs Healthcare System (VA). Nurses and physicians at 2 VA medical centers were trained to administer RT. A preimplementation formative evaluation was conducted at Site 1. Process evaluations of ongoing RT activities were conducted at Site 2. Interviews were conducted with key informants. Content and thematic analysis was conducted on the field notes. A variety of barriers and facilitators were discovered that impacted the implementation of NRT. Findings indicate concerns regarding training and incorporating NRT into workflow. Process interviews indicated that training concerns could be alleviated through various means. Finally, interviewees highlighted that other clinic settings might be a more preferred setting for NRT than primary care. Findings are currently being used for the implementation of additional NRT interventions, and can also guide NRT adoption in other facilities. PMID- 22060062 TI - Comment regarding the histopathology of terra firma-forme dermatosis. PMID- 22060063 TI - Clinical characterization of bvFTD due to FUS neuropathology. AB - In 2009, inclusions containing the fused in sarcoma (FUS) protein were identified as a third major molecular class of pathology underlying the behavioral variant frontotemporal dementia (bvFTD) syndrome. Due to the low prevalence of FUS pathology, few clinical descriptions have been published and none provides information about specific social-emotional deficits despite evidence for severe behavioral manifestations in this disorder. We evaluated a patient with bvFTD due to FUS pathology using a comprehensive battery of cognitive and social- emotional tests. A structural MRI scan and genetic tests for tau, progranulin, and FUS mutations were also performed. The patient showed preserved general cognitive functioning and superior working memory, but severe deficits in emotion attribution, sensitivity to punishment, and diminished capacity for interpersonal warmth and empathy. The gray matter atrophy pattern corresponded to this focal deficit profile, with preservation of dorsolateral fronto-parietal regions associated with executive functioning but severe damage to right worse than left frontoinsula, temporal pole, subgenual anterior cingulate, medial orbitofrontal cortex, amygdala, and caudate. This patient demonstrates the striking focality associated with FUS neuropathology in patients with bvFTD. PMID- 22060064 TI - Short-sightedness puts Australia at risk. PMID- 22060065 TI - NSAIDs and stroke risk. PMID- 22060066 TI - Multiresistant Escherichia coli in aged care: the gathering storm. PMID- 22060067 TI - A most trusted profession ...? PMID- 22060068 TI - Wind farms and health: who is fomenting community anxieties? PMID- 22060069 TI - Should doctors feel able to practise according to their personal views and beliefs?--Yes. PMID- 22060070 TI - Should doctors feel able to practise according to their personal values and beliefs?--No. PMID- 22060071 TI - Implementing electronic medication management at an Australian teaching hospital. AB - We describe the implementation of an electronic medication management system (eMMS) in an Australian teaching hospital, to inform future similar exercises. The success of eMMS implementation depends on: a positive workplace culture (leadership, teamwork and clinician ownership); acceptance of the major impact on work practices by all staff; timely system response to user feedback; training and support for clinicians; a usable system; adequate decision support. PMID- 22060072 TI - Borderline health: complexities of the Torres Strait treaty. PMID- 22060073 TI - A clinician's perspective on providing TB services in the Torres Strait. PMID- 22060074 TI - The slow-motion disaster that is breaking the bank. PMID- 22060075 TI - A Pandora's box: sustainable pharmaceutical supply. PMID- 22060076 TI - Doing the right thing for tuberculosis control in the Torres Strait Islands. PMID- 22060077 TI - Thunderstorm asthma--a timely reminder. PMID- 22060078 TI - Should opioids be used for chronic non-cancer pain? PMID- 22060079 TI - Is Australia ready to use glycated haemoglobin for the diagnosis of diabetes? PMID- 22060080 TI - Change of HbA1c reporting to the new SI units. PMID- 22060081 TI - Increasing ambulance demand requires enhanced indicators of quality and safety. PMID- 22060082 TI - Serious morbidity associated with misuse of over-the-counter codeine-ibuprofen analgesics. PMID- 22060083 TI - Death and morbidity from supratherapeutic dosing of colchicine. PMID- 22060084 TI - Practical neurology--4: Dizziness on head movement. AB - Benign positional vertigo (BPV) is the most common cause of episodic vertigo. It results from activation of semicircular canal receptors by the movement of calcium carbonate particles (otoconia) which dislodge from the otolith membranes. During changes in head position, the otoconia either float freely within the semicircular canal duct (canalithiasis) or adhere to and move with the cupula of the canal (cupulolithiasis). BPV from canalithiasis evokes brief spells of vertigo lasting seconds and can be diagnosed at the bedside by provoking paroxysmal vertigo and nystagmus on tilting the head in the plane of the affected canal. The nystagmus has a unique rotational axis perpendicular to the affected canal. The Dix-Hallpike test is a simple means of confirming the diagnosis in patients presenting with episodic vertigo or imbalance. Audiovestibular tests are only indicated if a symptomatic primary underlying inner ear disease is suspected. In over 80% of patients, BPV can be treated successfully with a single bedside Epley (particle-repositioning) manoeuvre, which can be performed by any medical practitioner. PMID- 22060085 TI - Cross-border patients with tuberculosis. PMID- 22060087 TI - Stroke risk and NSAIDs: an Australian population-based study. AB - OBJECTIVE: To determine the risk of stroke associated with non-steroidal anti inflammatory drug (NSAID) use. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of 162,065 Australian veterans with incident dispensing of an NSAID between 1 January 2001 and 31 December 2008, using prescription event sequence symmetry analysis. MAIN OUTCOME MEASURES: Hospitalisation for stroke, ischaemic stroke or haemorrhagic stroke. RESULTS: The absolute risk of stroke was low: 7.1/1000 people/year. Incident use of NSAIDs was associated with a 1.88 times increased risk (95% CI, 1.70-2.08) of hospitalisation for stroke (ischaemic or haemorrhagic) following first ever dispensing of an NSAID. This equates to an increased absolute risk of 13.4 strokes/1000 people/year. Significant positive associations between starting an NSAID and having a hospitalisation for stroke were found for most NSAIDs, with adjusted sequence ratios ranging from 1.44 (95% CI, 1.16-1.80) for indomethacin to 1.80 (95% CI, 1.59-2.04) for rofecoxib. CONCLUSIONS: Incident use of NSAIDs was associated with an increased risk of stroke. Increased awareness of the potential for serious adverse cardiovascular events, together with individual assessment of cardiovascular risk, careful deliberation of the balance between risk and benefits and appropriate supervision, is required when initiating NSAID therapy. PMID- 22060088 TI - Prevalence of antimicrobial-resistant organisms in residential aged care facilities. AB - OBJECTIVE: To assess the frequency of, and risk factors for, colonisation with vancomycin-resistant enterococci (VRE), Clostridium difficile and extended spectrum beta-lactamase (ESBL)-producing organisms in residential aged care facilities (RACFs). DESIGN, SETTING AND PARTICIPANTS: We conducted a point prevalence survey in October-November 2010 in three RACFs associated with our health service. A single faecal sample was collected from each participating resident and screened for the presence of VRE, C. difficile and ESBL-producing organisms. Presence of risk factors for antibiotic-resistant organisms was identified using a questionnaire. MAIN OUTCOME MEASURES: Prevalence of colonisation with VRE, C. difficile and ESBL-producing organisms; molecular typing of ESBL-producing organisms; prevalence of risk factors including presence of a urinary catheter, recent inpatient stay in an acute care setting and recent antibiotic consumption. RESULTS: Of 164 residents in the three facilities, 119 (73%) were screened. Mean age of screened residents was 79.2 years, and 61% were women; 74% had resided in the RACF for > 12 months, 21% had been given antibiotics within the past month and 12% had been in an acute care centre within the past 3 months. Overall rates of VRE (2%) and C. difficile (1%) colonisation were low, but ESBL-producing Escherichia coli was detected in 14 residents (12%) overall, with half of these residing in one wing of an RACF (27% of wing residents tested). Ten of the 14 ESBL-producing isolates had identical molecular typing patterns and belonged to genotye CTX-M-9. Eight of 13 residents had persistent colonisation on repeat testing 3 months later. CONCLUSION: We found a high prevalence of multiresistant ESBL-producing E. coli in RACF residents. A clonal relatedness of isolates suggests possible transmission within the facility. RACFs should have programs emphasising processes that will limit spread of these organisms, namely good hand hygiene compliance, enhanced environmental cleaning and dedicated antimicrobial stewardship programs. PMID- 22060089 TI - Is premigration health screening for tuberculosis worthwhile? AB - OBJECTIVE: To determine whether premigration screening for tuberculosis is worth undertaking in visa applicants, and whether screening resources are being appropriately directed towards intending migrants at highest risk of tuberculosis. DESIGN, SETTING AND PARTICIPANTS: A 12-month survey of all intending migrants with tuberculosis necessitating treatment detected during the premigration health assessment process, whose medical examinations were submitted to the Department of Immigration and Citizenship's Global Health Branch for assessment by a Medical Officer of the Commonwealth between 1 July 2009 and 30 June 2010. MAIN OUTCOME MEASURES: Individuals diagnosed with active tuberculosis; proportions diagnosed by sputum smear and culture tests or clinically, and with susceptibility test results; distribution of visa types among people diagnosed. RESULTS: In premigration assessments, 519 people were diagnosed with active tuberculosis (prevalence, 137 per 100,000 in examined population). The top source countries for people with tuberculosis were the Philippines (21.8%), India (16.8%), Vietnam (16.2%) and China (8.3%). Positive sputum smear test results were submitted for 67 cases (12.9%). Positive culture test results were obtained in 230 cases (44.3%), but only 95 of these (41.3%) had susceptibility test results, with 83 fully susceptible. Four people had multidrug-resistant tuberculosis (prevalence, 1.06 per 100 000 population). Five people had both active tuberculosis and HIV infection. Of all those diagnosed with tuberculosis, 162 (31.2%) were intending students, 82 (15.8%) were intending visitors, and 53 (10.2%) were applicants for humanitarian (refugee and Special Humanitarian Program) visas. CONCLUSIONS: Premigration health screening of intending migrants is identifying substantial numbers of people who would have required treatment for tuberculosis after arrival in Australia. The high proportion of students, visitors and refugee and humanitarian entrants with tuberculosis validates the current screening program. The screening is of benefit to the applicants, whose tuberculosis is treated earlier than it otherwise would have been, and to the Australian population, by averting exposure to people with active tuberculosis. PMID- 22060090 TI - Inpatient subacute care in Australia: perceptions of admission and discharge barriers. AB - OBJECTIVE: To determine perceptions of barriers to admission to subacute care from acute hospital care, and barriers to subsequent discharge from subacute care. DESIGN, PARTICIPANTS AND SETTING: Web-based survey of key stakeholders using Likert scales and closed questions. Prompts were emailed repeatedly to potential participants in Australia between 15 May and 24 July 2009. Participants were physicians working in inpatient rehabilitation medicine and aged care units, as well as senior hospital managers with responsibility for patient flow. MAIN OUTCOME MEASURES: Perceived admission and discharge barriers in subacute care. RESULTS: Half of the 101 respondents reported barriers to admission to subacute hospitals as moderate, severe or extreme, and 81% reported a similar grading of severity for barriers to discharge. There was no relationship between these perceptions and whether respondents worked only in the public hospital system (barriers to access: chi2 = 0.02 [df = 1; P = 1.0]; and barriers to discharge: chi2 = 0.0 [df = 1; P = 1.0]). The most commonly reported barriers to admission were: availability of beds (61% of respondents); physical, environmental and equipment inadequacies (62% of respondents); and allied health or nursing staff issues (55% of respondents). The most commonly reported barriers to discharge included: waiting for a more appropriate setting of care (76% of respondents) and funding for home modifications, equipment or carers (55% of respondents). There was no relationship between respondents' position and their reporting of various admission (chi2 = 6.2; df = 8; P = 0.6) or discharge barriers (chi2 = 13.8; df = 12; P = 0.3). CONCLUSION: There is a strong perception among key stakeholders in subacute care that there are major barriers to patient admission and discharge. Redistributing proposed funding for inpatient subacute beds to measures for overcoming these barriers is likely to improve patient flow though the whole hospital system. PMID- 22060091 TI - Flu fallout: what went wrong in 2010, and should we have seen it coming? PMID- 22060093 TI - The person inside. PMID- 22060096 TI - Structural studies of rigor bovine myofibrils using fluorescence microscopy. I. Procedures for purification and modification of bovine muscle proteins for use in fluorescence microscopy. AB - The myofibril is a fully competent fragment of the contractile apparatus of muscle, and its structure can be investigated with fluorescent-protein probes. Several purification and chemical modification techniques were developed for the synthesis of fluorescent myosin subfragment-1 (S1), actin and alphaactinin to be used as fluorescent probes of myofibril structure. Myosin was isolated from both rectus abdominis (RA) and cutaneus trunci (CT) and subjected to chymotryptic digestion to give S1 and myosin rod. Analysis of the time course of digestion by SDS-PAGE showed that S1 from RA myosin contained at least three heavy chain fragments while myosin from CT had essentially one. The S1 obtained from CT myosin was enzymatically characterized and used for fluorescent conjugation. Methods were adapted to conjugate thiol-specific fluorophores to actin, alpha actinin and S1. These fluorescent probes may be useful for structural studies on the isolated myofibril and on muscle in relation to its properties as a food. PMID- 22060097 TI - Structural studies of rigor bovine myofibrils using fluorescence microscopy. II. Influence of sarcomere length on the binding of myosin subfragment-1, alpha actinin and G-actin to rigor myofibrils. AB - Sarcomere length influences the textural quality of meat, yet the molecular basis for the mechanism of post-mortem shortening and the toughness associated with shortened muscle remain obscure. Bovine and rabbit myofibrillar structure was investigated over a range of sarcomere lengths (SL), using the high affinity of the myosin head for actin and of alpha-actinin for the Z-line. Myofibrils were incubated with fluorescent conjugates of myosin subfragment-1 (S1), alpha-actinin and actin. When S1 and alpha-actinin were added together, S1 bound in the I-band and A-band but not at the Z-line, while alpha-actinin bound at the Z-line. The pattern of S1 binding was highly influenced by SL, and could be explained using a model with the ratio of myofibrillar actin to myosin heads in the overlap region of 2:1 and thin filament penetration into opposing half sarcomeres. Double staining with S1 and actin demonstrated that, once the tip of the thin filament reached the bare zone, few intrinsic myosin heads were available for fluorescent actin. The patterns observed for both S1 and actin staining suggest that myofibrillar rigor bonds form even at very short SL. These observations lead to the hypothesis that the toughness associated with short sarcomeres is due to thick-filament interactions and not to the density of rigor bonds in the myofibril. Regulation of S1 binding was investigated by incubating myofibrils with low levels of fluorescent S1 in the presence and absence of calcium; S1 binding was in the overlap region when calcium was absent, but in the I-band when it was present. These results suggest that the thin filament can be activated for muscle shortening by the binding of myosin heads, a mechanism that may contribute to post-mortem muscle shortening. PMID- 22060098 TI - Performance, muscle composition and meat texture in veal calves administered a beta-agonist (clenbuterol). AB - The effect of clenbuterol administration on performance, muscle composition and meat texture was studied in veal calves. Three groups, of ten animals each, were assigned to the three following treatments for 27 days: control, administration of 0.3 and 1.0 ppm in the feed (dry matter basis). After a 14-day withdrawal period, the animals were slaughtered, and three muscles were sampled (M. longissumus thoracis; M. triceps brachii caput longum; M. rectus abdominis). During the period of clenbuterol administration, the treated calves exhibited a higher daily liveweight gain (DLWG) and a higher feed conversion efficiency (FCE) compared to those of the control calves, but these effects were reversed during the subsequent withdrawal period. At slaughter, the overall DLWG, FCE and carcass weight were similar in the three treatments, but the dressing percentage in the clenbuterol-treated calves was up to 5.7 points higher than that of the control calves. In the muscles studied, the clenbuterol had little effect on pH, sarcomere length, dry matter and nitrogen contents, collagen heat stability (solubility, isometric tension) or cooking loss; but it markedly reduced the content of lipids, collagen and haem pigments. The clenbuterol also affected myofibrillar strength after ageing, measured either on raw meat or on cooked meat. This was particularly evident in cooked meat which showed up to a two-fold increase in mechanical parameters (maximum stress, compression modulus) after the clenbuterol treatment. No dose effect was detected except for the mechanical parameters. It was concluded that clenbuterol administration affects, meat in two opposite ways, viz. a marked toughening effects, due to a reduction in the muscle ageing rate, that is not compensated by a concomitant tenderizing effect (through a decrease in the intramuscular collagen content). PMID- 22060099 TI - Extended shelf-life of unrefrigerated prerigor cooked meat. AB - Five experiments were conducted to evaluate the microbial quality of unrefrigerated cooked prerigor beef after the application of oxygen-permeable packaging. Specific objectives were to combine the beneficial effects of aerobic packaging, meat surface acidification and prerigor rapid cooking rates on meat storage stability at ambient temperature. In the experiments, the triceps brachii muscle was dissected from one side 45 min after exanguination of the animal, and samples of 2 * 3 * 5 cm were prepared. Bags made of a strong barrier, plastic film, and a highly oxygen permeable oriented polypropylene, were used. The cooking of the packaged samples covered a number of treatments ranging from cooking in a 70 degrees C water bath to an internal sample temperature of 65 degrees C to cooking in 100 degrees C water for 40 min. Reheating and multiple heat treatments were also included. The pH values of the cooked samples were determined and aerobic plate counts (log(10)/g) were determined for the cooked samples at various intervals during two weeks of storage at 22 degrees C or at 3 degrees C for the control samples. The results indicate that heat treatment alone did not improve shelf stability at 22 degrees C. However, dipping the samples in 80 degrees C solutions of 0.7% citric acid or 1.25% lactic acid for 1 min and draining for 1 min followed by packaging using oxygen permeable bags and cooking in 100 degrees C water for 40 min consistently resulted in shelf stable products at all 22 degrees C storage intervals. The lactic acid treatment was superior to the citric acid treatment because it completely decontaminated the samples and delayed spoilage, especially at 3 degrees C. PMID- 22060100 TI - Effects of feeding diets containing different fat supplements to swine on the visual properties and storage stability of low-fat sausage. AB - Sixty barrows and gilts were assigned to one of five dietary treatments consisting of a control diet of corn and soybean meal and four similar test diets that contained a 10% replacement of either animal fat, safflower oil, sunflower oil or canola oil, to determine the effects of high levels of oleic acid in the diet of swine on the storage stability of fresh pork sausage. Pork trim from each treatment was used to formulate sausage that contained two fat levels (25% and 35%), and two levels of added water (3% and 11%). Thiobarbituric acid values did not differ between the control, safflower oil or sunflower oil treatments and all treatments were acceptable after 10 weeks of storage. Microbial numbers increased with the level of added water and during time in storage (up to 3 weeks). Visual evaluation showed that the control was the most red and least discolored, while the canola oil treatment was the least red and the most discolored. Results from the present study suggest that a 105 replacement of a typical corn/soybean meal diet to swine with safflower or sunflower oil did not alter the storage-stability of fresh pork sausage. PMID- 22060101 TI - Effect of residual oxygen on the colour, odour and taste of carbon dioxide packaged beef, lamb and pork during short term storage at chill temperatures. AB - Samples of boneless pork, lamb, beef (high and normal pH) were packaged in '100%' carbon dioxide atmospheres in foil laminate pouches. These pouches were fitted with a septum and a gas sampling port that allowed the introduction of air and removal of gas samples for analysis from the sealed packs. After sealing, measured volumes of air were introduced into test packs that had been gassed at a carbon dioxide volume to meat weight ratio of either 1 litre/kg or 2 litres/kg, to give initial atmospheres containing approximately 0.1, 0.2 and 1.0% oxygen. After 24 and 168 h storage at -1.5 +/- 0.5 degrees C, test packs were removed and compared with similarly treated control packs without added oxygen with respect to meat odour, taste and colour. No significant differences between the test and control packs in respect to odour or taste were evident with any meat type. The tendency to develop browning in response to the presence of residual oxygen within packs, increased in the order: pork, normal pH beef, normal pH lamb, high pH beef. Beef and lamb developed noticeable browning in packs containing more than 0.15% total oxygen while pork was able to tolerate 1% oxygen without obvious detrimental effects. For all meat types, the colour stability was greater in packs gassed to the higher gas volume to meat weight ratio. PMID- 22060102 TI - The relationship between ATP and R-values in postmortem bovine Longissimus dorsi muscle. AB - To study the relationship between ATP and each of three R-values (R248, R250 and R258) in beef longissimus dorsi muscle data, appropriate mathematical functional forms were estimated by the Box-Cox transformation and then tested for linearity. Two separate tests for linearity indicated that the relationships between ATP and the three R-values were nonlinear. A shifting parameter restriction on the Box Cox model was used to produce a curve that was more parallel to the y axis in the lower range of x axis, but the restriction lowered the R(2) compared with the Box Cox model. ATP (1 MUmol) could be estimated by R248 of 0.925, R250 of 0.967 and R258 of 1.038 with standard errors of 0.033, 0.034 and 0.032, respectively. There were no significant differences among the three R-values for the prediction of ATP, but there was a suggestion that R258 was the preferred R-value for predicting ATP in beef muscle. PMID- 22060103 TI - Calcium chloride marination effects on beef steak tenderness and calpain proteolytic activity. AB - A study was conducted in three phases to examine the effect of calcium chloride marination on tenderness. Steaks obtained 5 days postmortem were marinated in a 150 mM calcium chloride solution for 24 h and 48 h in phase 1, and for 48 h in phases 2 and 3. The steaks utilized were obtained from mature cows 8-11 years of age-phase 1; four control and four beta-agonist fed steers-phase 2; and three Peidmontese and two Nelore 18-month-old steers-phase 3. Data were analyzed by analysis of variance for a split-plot design. In phase 1, marination failed to improve (P > 0.05) shear force values. However, shear force values were less than 5 kg which was uncommonly low for mature cows. In phase 2, marination improved (P < 0.05) meat tenderness regardless of diet. Yet, the steaks from the beta-agonist fed steers remained less tender, even after marination, than the steaks from the control steers. In phase 3, shear force requirements were decreased (P < 0.01) with marination. Also, the activities of m-calpain and calpastatin decreased (P < 0.05) with calcium marination. It appeared that the improvement in tenderness was through the activation of m-calpain. PMID- 22060104 TI - Detection of farnesyltransferase interface hot spots through computational alanine scanning mutagenesis. AB - In this study, we present a detailed characterization of the full alpha/beta interface in the farnesyltransferase (FTase) enzyme, an important target in drug design efforts. This characterization is presented in terms of hot spots, warm spots, and null spots and is based on the application of an improved variation of the computational alanine scanning mutagenesis methodology, complemented with extensive solvent-accessible surface area and interfacial hydrogen-bonding analysis. A total of 130 interface amino acid residues were considered in this analysis, a number that represents 16.0% of the total of 814 amino acid residues in the full enzyme. Globally, the results provide important clues on the most important structural and energetic determinants for dimer formation, suggesting several key targets at the subunit interface for the development of new molecules that aim to inhibit FTase activity through blocking the formation of the fully active FTase dimer, yielding useful indications for future drug design efforts. PMID- 22060105 TI - Slow-release insulin in cystic fibrosis patients with glucose intolerance: a randomized clinical trial. AB - BACKGROUND: Early stages of glucose metabolism impairment are a period at risk in the long-term prognosis of cystic fibrosis (CF). Slow-release synthetic insulin glargine can be a therapeutic tool in this metabolic condition. METHODS: In this phase 3 multicenter, controlled, two-arm, randomized clinical study, glargine was administered up to a dosage of 0.15 U/kg/die for a period of 18 months. Primary endpoint was the improvement of nutritional status [body mass index (BMI) Z score], while glucose tolerance [hemoglobin A1c (HbA1C) and respiratory function (FEV1 predicted] improvement were the secondary endpoints. RESULTS: Thirty-four subjects (18 in the glargine arm and 16 in the control arm) were evaluated. Adherence to insulin treatment was excellent. No significant adverse events were reported. There were no significant differences in BMI, HbA1C and FEV1 values between the two groups nor within groups, except for HbA1C improvement in the glargine arm at month +18 (p = 0.04). CONCLUSIONS: Glargine treatment was well accepted and tolerated. No real efficacy in improving clinical and glycometabolic conditions was demonstrated. Further studies are necessary to test glargine at higher dosage and for a longer follow-up period. PMID- 22060106 TI - A PORR domain protein required for rpl2 and ccmF(C) intron splicing and for the biogenesis of c-type cytochromes in Arabidopsis mitochondria. AB - Angiosperm mitochondria encode approximately 20 group II introns, which interrupt genes involved in the biogenesis and function of the respiratory chain. Nucleus encoded splicing factors have been identified for approximately half of these introns. The splicing factors derive from several protein families defined by atypical RNA binding domains that function primarily in organelles. We show here that the Arabidopsis protein WTF9 is essential for the splicing of group II introns in two mitochondrial genes for which splicing factors had not previously been identified: rpl2 and ccmF(C). WTF9 harbors a recently recognized RNA binding domain, the PORR domain, which was originally characterized in the chloroplast splicing factor WTF1. These findings show that the PORR domain family also functions in plant mitochondria, and highlight the parallels between the machineries for group II intron splicing in plant mitochondria and chloroplasts. In addition, we used the splicing defects in wtf9 mutants as a means to functionally characterize the mitochondrial rpl2 and ccmF(C) genes. Loss of ccmF(C) expression correlates with the loss of cytochromes c and c1, confirming a role for ccmF(C) in cytochrome biogenesis. By contrast, our results strongly suggest that splicing is not essential for the function of the mitochondrial rpl2 gene, and imply that the Rpl2 fragment encoded by rpl2 exon 1 functions in concert with a nuclear gene product that provides the remainder of this essential ribosomal protein in trans. PMID- 22060107 TI - Influence of production system on carcass characteristics of F(1) Wagyu * Angus steers and heifers. AB - American Wagyu * Angus steers (n = 15) and heifers (n = 26) were finished to typical Japanese market weight and degree of finish using two different feeding methods. The first method (deferred) consisted of two growing/ finishing phases: a forage-based diet for approximately 8 months followed by a high concentrate diet fed ad libitum for an additional 8 months while the second finishing method (linear) was designed to produce a linear rate of gain for the entire 16 months that the cattle were on feed. Even though there were substantial differences in daily weight gain (P < 0.05) within the two growing/finishing phases, total weight gain for the entire 16 months was not different between the two feeding methods (P > 0.05). Cattle produced by the linear growth method were superior to deferred growth cattle for carcass weight (as estimated by cold left side weight), rib thickness, dressing percentage, marbling score, fat color, fat luster, fat quality, as well as in scores for meat color, brightness, firmness and texture (P < 0.05). Fat thickness was not affected by treatment (P > 0.05). These data indicate that the linear method of production is more consistent with producing carcasses for the Japanese beef market. PMID- 22060108 TI - Determinants of tenderisation in beef Longissimus dorsi and Triceps brachii muscles. AB - Tenderisation of bovine Mm. longissimus dorsi and triceps brachii and factors impacting tenderisation were studied. Mm. longissimus dorsi and triceps brachii of 12 Friesian-Holstein cows (age 3-11 years; 212-349 kg carcass weight) were sampled at various times post mortem (p.m.) for determination of pH, temperature, fibre type and morphology, connective tissue distribution, SDS-PAGE of myofibrillar proteins, Warner-Bratzler shear force, sarcomere length and osmolality. The stretched position of the M. triceps brachii (sarcomere length 2.35 +/- 0.24 MUm) resulted in a relatively low shear force at 1 day p.m. (6.2 +/ 0.9 kg/cm(2)) with further storage having little additional effect. M. longissimus dorsi entered rigor in a more contracted state (sarcomere length 1.65 +/- 0.11 MUm), resulting in a relatively high shear force at 1 day p.m. (10.3 +/- 2.3). Stepwise linear regression was used to calculate the best 1- to 3-variable equations for shear force of M. longissimus dorsi at 1, 7 and 14 days p.m. and the decrease in shear force between 7 and 14 days p.m. Shear force at 1 day p.m. appeared to be determined mainly by the speed of pH- and temperature-decline. Proteolysis of myofibrillar proteins and animal age appeared to be the main determinants for shear force at 1 and 14 days p.m. The average surface area of type I fibres could explain part of the variation in the decrease in shear force between 1 and 14 days p.m. PMID- 22060109 TI - The use of oxygen scavengers to prevent the transient discolouration of ground beef packaged under controlled, oxygen-depleted atmospheres. AB - Rates of O(2) absorption from air were determined for a type of commercial O(2) scavenger that is formulated for rapid O(2) absorption at chiller temperatures. Rates of O(2) absorption from N(2) atmospheres containing 600 ppm O(2) were determined for trays that each contained 350 g of ground beef. Packs with controlled atmospheres of N(2) that contained ground beef and O(2) scavengers were prepared, to determine the conditions under which the scavengers could prevent the transient discolouration of the meat which arises from its reaction with the residual O(2) initially present in pack atmospheres. The rates of O(2) absorption by individual scavengers varied from the average by +/-50%. The rate of O(2) absorption declined with decreasing oxygen concentration, from an average value per scavenger of about 12 ml h(-1) when O(2) concentrations were between 20 and 10%. At O(2) concentrations <1% (10,000 ppm) the rate of O(2) absorption was directly proportioned to the O(2) concentration so that the O(2) concentration in an atmosphere in a gas-impermeable pouch declined exponentially with time. The absorption of O(2) by ground beef was similarly dependent on the O(2) concentration. At 2 degrees C, the transient discolouration of beef in atmospheres initially containing about 50 ppm O(2) was prevented by the presence of 17.5 scavengers per l of atmosphere. At -15 degrees C, discolouration was prevented by 5 scavengers per l. The findings indicate that the O(2) concentration in pack atmospheres has to be reduced below 10 ppm within 30 min at 2 degrees C, or 2 h at -1.5 degrees C if ground beef is not to transiently discolour. It is unlikely that the required rates of O(2) absorption could be obtained economically with currently available, commercial O(2) scavengers. PMID- 22060110 TI - Organ weights, muscle composition and fatty acid profiles in lambs fed salbutamol: Effect of a 5-day withdrawal period. AB - Lambs were fed ad libitum on a diet containing the beta-adrenergic agonist salbutamol (2 ppm) for 38 days to investigate its effects on organ weights, muscle composition and fatty acid profiles. The influence of a 5-day withdrawal period was also assessed. The oral administration of salbutamol did not increase muscle weights and no differences were found in liver, heart and lung proportions. However, kidney weight was higher in the salbutamol-not-withdrawn animals. In treated animals fat and collagen levels decreased (P < 0.05), while protein increased (P < 0.05) in the semitendinosus (ST) muscle when compared to controls. However, no effects of the beta-agonist treatment were found in the longissimus dorsi (LD) muscle. Intramuscular LD polyunsaturated fatty acids were higher (P < 0.05). Subcutaneous adipose tissue samples were higher (P < 0.05) in total unsaturated fatty acids and lower (P < 0.05) in total saturated fatty acids. All these changes in the fatty acid profiles of both intramuscular and adipose tissues were more marked after the 5-day salbutamol withdrawal period. PMID- 22060111 TI - Sorbic acid stability in meat products of reduced water activity. AB - This study investigated the behavior of sorbic acid in shelf-stable meats with 0.91 water activity during processing (70 degrees , 80 degrees , 90 degrees C) and accelerated storage (33 degrees , 45 degrees , 57 degrees C). In meat systems stored at 70 degrees , 80 degrees and 90 degrees C, after approximately 0.5-3 days, the destruction rate of sorbic acid diminished. This change in behavior (break) was probably caused by the limited availability of oxygen and/or the inhibitory action of nonenzymatic browning products on sorbate destruction. Before the break, the rate constants were found to be related to temperature, pH, the acid used to adjust it and the humectants added to depress water activity (NaCl, glycerol, the mixture NaCl 3.5% and glycerol). After the break, none of the above mentioned effects were observed. In meat systems stored at 33 degrees , 45 degrees and 57 degrees C the rate of destruction was constant with time. The rate constants of meat systems were higher than the ones obtained for aqueous systems of similar composition, revealing that meat components played an important role in the destruction of sorbates. PMID- 22060112 TI - Implant and biological type effects on beef carcass characteristics. AB - Beef carcasses (n = 1574) were evaluated at Excel Corp. beef slaughtering facility, Friona, Texas, to determine the effects of implants (double Revalor and Ralgro/Revalor) and biological type (Continental European, Continental European * British and British) on carcass characteristics. No differences (P > 0.05) were found between implants for marbling score, USDA quality grade, adjusted preliminary yield grade, percentage kidney, pelvic and heart fat, or carcass weight. Carcasses from cattle implanted with double Revalor had a larger (P < 0.05) ribeye area and a lower USDA yield grade. No differences were found among breed types for marbling score, USDA quality grade, preliminary yield grade, ribeye area or USDA yield grade (P > 0.05). Steers classed as continental European had the lowest adjusted preliminary yield grade and percentage kidney, pelvic and heart fat, the heaviest carcasses and were most muscular as determined by the Excel muscle score (P < 0.05). PMID- 22060113 TI - Potential interactions between the effects of preslaughter stress and post-mortem electrical stimulation of the carcasses on meat quality in pigs. AB - The experiment examined the influence on pork quality of the electrical stimulation of carcasses from pigs subjected to different ante-mortem handling treatments. The carcasses were subjected to a slow chilling regimen to reflect less than ideal commercial practice. A total of 288 pigs (mean live weight 89 kg) of both sexes and a range of genotypes were used. They came from the Meat and Livestock Commission 's Pig Development Unit at Stotfold and were processed in 12 equal batches. Prior to slaughter they were transported for 2 h (80 km) at a stocking density of 0.5 m(2)/100 kg live weight. Preslaughter handling included being mixed or not with unfamiliar animals and being given a 3 h rest in lairage or not. One group received handling to simulate that in stunning races immediately before slaughter. There were no material interactions between the effects of ante- and post-mortem handling. Pigs rested 3 h in lairage had lower plasma cortisol levels irrespective of whether mixed with unfamiliar animals. Plasma lactate concentrations increased with greater ante-mortem stress. Pigs subjected to the simulated stunning race treatment had elevated carcass temperature. Greater ante-mortem stress progressively elevated pHu in the muscles and tended to reduce eating quality. Electrical stimulation followed by slow chilling raised initial muscle temperature, reduced pH(45) and pHu, and produced meat that was paler, had higher hue and saturation values and lost more drip during storage. Neither instrumentally-determined texture nor taste panel texture was affected, but electrical stimulation decreased juiciness and increased pork flavour. Overall eating quality was not affected by stimulation. PMID- 22060114 TI - Fatty acids in carcass fat of steers treated with a beta-adrenergic agonist individually or in combination with trenbolone acetate + oestradiol-17beta. AB - Forty steers of medium maturity were allocated randomly to four treatment groups of 10 steers each (C = Control, betaA = beta-Agonist, TO = Trenbolone acetate + oestradiol-17beta and betaTO = beta-Agonist in combination with trenbolone acetate + oestradiol-17beta). After 56 days on treatment, the beta-Agonist treatment was stopped and the steers slaughtered on the ninth day after withdrawal. Samples of subcutaneous fat over the 13th rib and M. longissimus dorsi were stored in sealed polyethylene bags at -20 degrees C for fatty acid analysis. A greater proportion of oleic acid (C18: 1, P < 0.05) was deposited in the subcutaneous fat of steers treated with betaA as opposed to those treated with either TO or betaTO. Treatments altered the fatty acid composition of the M. longissimus dorsi, particularly through their effects on palmitic acid (C16:0, P < 0.01), palmitoleic acid (C16:1, P < 0.01) and oleic acid (C18:1, P < 0.01). The results suggest a shift (P < 0.01) towards saturated fatty acids in the M. longissimus dorsi of steers treated with either betaA or betaTO. PMID- 22060115 TI - Differences in the electrophoretic patterns of soluble pork proteins as a consequence of pig rearing conditions. AB - In recent years the importance of 'organic meat' has increased. Rigorous rearing conditions has raised the emphasis on meat quality problems. Pigs (genotype: Hungarian Large White 75% and Mangalica, pigs with curly bristles, 25%) were kept in a natural farming system, and did not receive growth promoters, hormones or antibiotics. The meat of these pigs is called 'organic meat', or 'bio meat'. Longissimus dorsi muscles of pigs kept under natural circumstances and under traditional conditions were compared using SDS polyacrylamide gel electrophoresis and isoelectric focusing. Electrophoretic separation, protein and esterase enzyme staining showed definite differences between the proteolysates of organic and control meat samples. PMID- 22060116 TI - Effects of live animal performance and hemoglobin level on special-fed veal carcass characteristics. AB - Growth and carcass characteristics were measured on 975 Holstein bull calves raised on four commercial veal farms (nine feeding groups). Average values for blood hemoglobin (Hb), live weight and gain, dressing percentage (DP; hide-on and hide-off), visual muscle color score, rib-eye-area (REA), and carcass conformation score were 7.8 g/dl, 187.1 kg, 1.46 kg/d, 67.4%, 60.4%, 1.42, 42.0 sq cm, and 11.7, respectively. Carcass weights averaged 127.6 and 112.4 kg for hide-on and hide-off, respectively. There were few significant correlations of Hb with growth performance, carcass weight or DP. Pre-slaughter Hb was correlated 0.54 (P < 0.01) with flank muscle color score. Calves which were either heavier or which gained weight more rapidly tended to have slightly lower muscle color scores, larger REA and higher carcass conformation scores. Results from this study suggest that pre-slaughter Hb levels are higher than previously reported in specialfed veal, and there is no apparent relationship of Hb value, red blood cell count or mean corpuscular hemoglobin with growth performance traits. Although final Hb values were moderately predictive of muscle color score (accounting for 29% of the within-group variance), apparently there are other factors both within and between farms which influence muscle color in special-fed veal carcasses. PMID- 22060117 TI - An efficient method for the isolation of intramuscular collagen. AB - Ultrasonic fragmentation of the myofibrils and subsequent solubilisation in buffer has been used to isolate intramuscular collagen (IMC) in high yield and purity. The method is superior to previously reported techniques in providing both a high yield of collagen and intact fibres. The material obtained is suitable for both physical and biochemical analysis in attempts to demonstrate its role in determining the tenderness of meat. PMID- 22060118 TI - Functional polymer laminates from hyperthermal hydrogen induced cross-linking. AB - The use of a hyperthermal hydrogen induced cross-linking process to prepare laminates comprising polypropylene, poly(isobutylene-co-isoprene), and poly(vinyl acetate) is described. In this new, milder alternative to conventional plasma techniques, neutral molecular hydrogen projectiles were used to create carbon radicals on impacted surfaces by collision-induced dissociation of C-H bonds, and this process was used to cross-link polymers on a polypropylene surface. It was demonstrated that multiple layers of cross-linked materials could be added, creating polymer laminates with each layer introducing new functionalities and properties. In particular, the present work shows that the process is largely nondestructive toward ester functionalities. First, the esters were grafted to become nonleachable. Then, the esters were subsequently hydrolyzed to convert the surface from hydrophobic to hydrophilic. Afterward, the esters could be recovered by simple esterification demonstrating that further chemical transformations were possible. PMID- 22060119 TI - Field modulation in Na-incorporated Cu(In,Ga)Se2 (CIGS) polycrystalline films influenced by alloy-hardening and pair-annihilation probabilities. AB - The influence of Na on Cu(In,Ga)Se2 (CIGS) solar cells was investigated. A gradient profile of the Na in the CIGS absorber layer can induce an electric field modulation and significantly strengthen the back surface field effect. This field modulation originates from a grain growth model introduced by a combination of alloy-hardening and pair-annihilation probabilities, wherein the Cu supply and Na diffusion together screen the driving force of the grain boundary motion (GBM) by alloy hardening, which indicates a specific GBM pinning by Cu and Na. The pair annihilation between the ubiquitously evolving GBMs has a coincident probability with the alloy-hardening event.PACS: 88. 40. H-, 81. 10. Aj, 81. 40. Cd. PMID- 22060120 TI - Photoinduced electron-transfer-promoted redox fragmentation of N alkoxyphthalimides. AB - A new photoinduced electron-transfer-promoted redox fragmentation of N alkoxyphthalimides has been developed. Mechanistic experiments have established that this reaction proceeds through a unique concerted intramolecular fragmentation process. This distinctive mechanism imparts many synthetic advantages, which are highlighted in the redox fragmentation of various heterocyclic substrates. PMID- 22060122 TI - Incorporation of 15N-labeled ammonia into glutamine amide groups by protein glutaminase and analysis of the reactivity for alpha-lactalbumin. AB - Protein-glutaminase (PG) is an enzyme that catalyzes the deamidation of protein bound glutamine residues. We found that an enzyme labeling technique (ELT), which is a stable isotope labeling method based on transglutaminase (TGase) reaction, is applicable for PG. PG catalyzed incorporation of (15)N-labeled ammonium ions into reactive glutamine amide groups in alpha-lactalbumin similarly to TGase and deamidated the most reactive glutamine amide group once labeled with (15)N. Furthermore, we investigated the effect of ammonium ions on the PG activity by peptide mapping, and more reactive glutamine residues were detected than were detected by the ELT in the presence of ammonium ions. This is probably because ammonium ions are competitive inhibitors, causing decreased reactivity for glutamine residues. We propose the reaction scheme of PG in the presence of the (15)N-labeled ammonium ions and show that the ELT method with PG is useful for evaluating the activity of PG. PMID- 22060123 TI - American political affiliation, 2003-43: a cohort component projection. AB - The recent rise in identification with American political parties has focused interest on the long-term dynamics of party support. Liberal commentators cite immigration and youth as forces that will produce a natural advantage for the Democrats in the future, while conservative writers highlight the importance of high fertility amongst Republicans in securing growth. These opinions are not based on demographic analysis. We addressed this omission by undertaking the first ever cohort component projection (up to 2043) of populations by American party allegiance, based on survey and census data. On current trends, we predict that American partisanship will change much less than the nation's ethnic composition because the parties are similar in age structure. Nevertheless, our projections suggest that the Democrats will gain 2-3 per cent more support than the Republicans by 2043, mainly through immigration, although the higher fertility of Republicans may eventually offset that advantage. PMID- 22060124 TI - Social suffering and anxiety: deciphering coughs and colds at Akan anti witchcraft shrines in Paris. AB - In treating illness and suffering, the Akan anti-witchcraft shrine is often presented as a model of unchanging, tightly bounded and antiquated ideals. This fails to acknowledge the extensive repertoire of Ghanaian witchcraft discourses and contemporary divinatory practices uncovered at Akan anti-witchcraft shrines. This paper analyses how one of the most popular Akan anti-witchcraft shrine in Europe, in an eastern banlieue of Paris, diagnoses the seemingly common and innocuous coughs and colds suffered by recently arrived, unskilled female Ghanaian migrants as something more socially and economically malignant, witchcraft. Successful treatment combines divinatory techniques, paracetamol medicines and positive thinking in order to empower clients and present them with the possibility of new social and gainful employment prospects. PMID- 22060125 TI - Pregnancy decision-making among HIV positive women in Northern Vietnam: reconsidering reproductive choice. AB - The global HIV epidemic confronts pregnant women with hard reproductive choices. This paper offers a theoretically innovative and ethnographically sensitive exploration of the social processes through which 20 HIV positive women living in Northern Vietnam decide whether to continue or terminate their pregnancies. Arguing that human agency must be seen as an outcome of intersubjective engagements in shared social worlds, this paper explores how these women came to the decisions that they had to make and shows that women's choices were configured through everyday social relations, shaped through intimate engagements with husbands, parents, siblings, and in-laws. Based on the findings, it is recommended that pregnancy counseling is offered not only to the woman herself, but also, if she desires, involves members of her extended family. PMID- 22060126 TI - Suffering of childless women in Bangladesh: the intersection of social identities of gender and class. AB - Research has documented that, around the world, women who are childless against their will suffer from an array of social, economic and emotional difficulties. The causes of this suffering are primarily related to their gender position in society and their gender identity. This paper addresses the impact of class differences on the gender-related suffering of childless women in the socially very hierarchically structured society of Bangladesh. The main method was gathering life histories of illiterate rural poor childless women and educated urban middle-class childless women. The rural childless women experience strong stigma in society, as their identity is devalued due to their inability to produce children. As a result, they suffer from feelings of guilt, role failure, loss of self-esteem, abandonment by the family, social isolation, and impoverishment. In contrast, because of their relatively high socio-economic status and good educational background, urban childless women have more opportunities to avail themselves of alternative social identities and thus avoid social isolation. Despite these differences, both groups of women lead frustrated lives, burdened with a deep sense of guilt for not being able to produce children. PMID- 22060127 TI - 'It is only a pinprick': (or is it?): childhood vaccinations in general practice as 'matter out of place'. AB - The analysis presented in this paper is part of a larger study, the aim of which is to describe the GPs' everyday taken-for-granted working life. The study is based on multi-sited anthropological fieldwork in Danish general practices. This paper analyses consultations where children are vaccinated and the analysis shows the way these consultations differ from other consultations in relation to flow and communication. Neither parents nor doctors question the value of the vaccination, but the manner in which they talk about it and handle it in the flow of the consultation points to them experiencing it as being problematic. Taking inspiration from Mary Douglas' theory on cultural classification the injection is interpreted as 'matter out of place'. The analysis identifies the infliction of pain and the discomfort this brings to the doctor and the parent as problematic as well as a breach of the doctor-patient relationship. The aim of vaccination is to prevent potential diseases in the future, but its function in the consultation, besides being fulfilment of national guidelines, is not immediately apparent. It has no real function in the consultation and this makes it problematic in the present, causing the ambiguity that both doctors and parents express. PMID- 22060128 TI - A cultural model of infidelity among African American and Puerto Rican young adults. AB - Having concurrent sexual partners is a risk factor for STIs and HIV/AIDS, yet few studies have investigated the cultural meanings and functions of concurrency. A multi-method qualitative/quantitative study of sexual ideas, attitudes, and behaviors among inner-city Puerto Rican and African American emergent adults (age 18-25) in Hartford, Connecticut, USA, suggests that having concurrent partners is common in this population. Using data from 12 focus groups and 40 participants in systematic data collection techniques (e.g., pile sorts), the underlying cognitive structure of concurrency and cheating/infidelity are explored. Results suggest that participants are less tolerant of multiple partners in more committed relationships, but that very few relationships can be considered committed. Furthermore, participants see cheating as inevitable even in committed relationships. Sexual transgressions are considered the most severe form of cheating. Having an outside partner for emotional reasons or to have access to one's child were seen as more acceptable/forgivable than doing so for sexual satisfaction, social status or material goods. Multiple partnerships must be seen in the context of the inner city where resources and opportunities are scarce and young adults attempt to protect themselves from emotional injury. Documenting new and changing social constructions of infidelity is important for understanding the social context of sexual behavior in our global world and for designing culturally appropriate health interventions. PMID- 22060132 TI - Multiplexed method to calibrate and quantitate fluorescence signal for allergen specific IgE. AB - Using a microarray platform for allergy diagnosis allows for testing of specific IgE sensitivity to a multitude of allergens, while requiring only small volumes of serum. However, variation of probe immobilization on microarrays hinders the ability to make quantitative, assertive, and statistically relevant conclusions necessary in immunodiagnostics. To address this problem, we have developed a calibrated, inexpensive, multiplexed, and rapid protein microarray method that directly correlates surface probe density to captured labeled secondary antibody in clinical samples. We have identified three major technological advantages of our calibrated fluorescence enhancement (CaFE) technique: (i) a significant increase in fluorescence emission over a broad range of fluorophores on a layered substrate optimized specifically for fluorescence; (ii) a method to perform label free quantification of the probes in each spot while maintaining fluorescence enhancement for a particular fluorophore; and (iii) a calibrated, quantitative technique that combines fluorescence and label-free modalities to accurately measure probe density and bound target for a variety of antibody-antigen pairs. In this paper, we establish the effectiveness of the CaFE method by presenting the strong linear dependence of the amount of bound protein to the resulting fluorescence signal of secondary antibody for IgG, beta-lactoglobulin, and allergen-specific IgEs to Ara h 1 (peanut major allergen) and Phl p 1 (timothy grass major allergen) in human serum. PMID- 22060134 TI - Clinical validation of the Acuros XB photon dose calculation algorithm, a grid based Boltzmann equation solver. AB - INTRODUCTION: A new algorithm that uses a grid-based technique to solve the linear Boltzmann transport equation (LBTE) has been developed to improve the accuracy and speed of external photon beam treatment planning calculations. The aim of this study was to test the accuracy of this algorithm in both heterogeneous and homogeneous media. MATERIAL AND METHODS: Output factors, depth dose curves and profiles for symmetric fields were measured in water using diamond and ionization chamber detectors. Furthermore, asymmetric fields, fields collimated with the multi-leaf collimator, enhanced dynamic wedge fields as well as fields with different source-skin distances were measured. Various test plans were created on a CIRS thorax phantom including tissue-equivalent inserts and corresponding dose distributions within the phantom were measured with radiochromic films. The new grid-based LBTE solver, Acuros XB (Eclipse version 10.0, Varian Medical Systems, CA, USA) was used to calculate dose distributions for all field configurations and plans, for both 6 MV and 15 MV photons. Calculations were also performed with AAA, a standard convolution algorithm. RESULTS: Compared to measurements, the output factors were within 1% for Acuros XB. For the depth doses, the average deviations were within 1% in dose and 1 mm in distance to agreement (DTA). For the profiles, the deviations were within 2%/1 mm except near the penumbra. Similar results were obtained for the other field configurations. Good agreement with AAA was also found. For the plans calculated on the CIRS phantom, the number of points meeting the gamma criterion of 3% in dose and 3 mm in DTA was higher with Acuros XB (98% for 6 MV; 100% for 15 MV) than with AAA (94% for 6 MV; 96% for 15 MV). CONCLUSION: Dose calculations with the Acuros XB algorithm in homogeneous media are in good agreement with both measurements and the AAA algorithm. In heterogeneous media, the Acuros XB algorithm is superior to AAA in both lung and bony material. PMID- 22060133 TI - alpha-Synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases. AB - Intracellular deposition of fibrillar aggregates of alpha-synuclein (alphaSyn) characterizes neurodegenerative diseases such as Parkinson's disease (PD) and dementia with Lewy bodies. However, recent evidence indicates that small alphaSyn oligomeric aggregates that precede fibril formation may be the most neurotoxic species and can be found extracellularly. This new evidence has changed the view of pathological alphaSyn aggregation from a self-contained cellular phenomenon to an extracellular event and prompted investigation of the putative effects of extracellular alphaSyn oligomers. In this study, we report that extracellular application of alphaSyn oligomers detrimentally impacts neuronal welfare and memory function. We found that oligomeric alphaSyn increased intracellular Ca(2+) levels, induced calcineurin (CaN) activity, decreased cAMP response element binding protein (CREB) transcriptional activity and resulted in calcineurin dependent death of human neuroblastoma cells. Similarly, CaN induction and CREB inhibition were observed when alphaSyn oligomers were applied to organotypic brain slices, which opposed hippocampal long-term potentiation. Furthermore, alphaSyn oligomers induced CaN, inhibited CREB and evoked memory impairments in mice that received acute intracerebroventricular injections. Notably, all these events were reversed by pharmacological inhibition of CaN. Moreover, we found decreased active CaN and reduced levels of phosphorylated CREB in autopsy brain tissue from patients affected by dementia with Lewy bodies, which is characterized by deposition of alphaSyn aggregates and progressive cognitive decline. These results indicate that exogenously applied alphaSyn oligomers impact neuronal function and produce memory deficits through mechanisms that involve CaN activation. PMID- 22060135 TI - Radiation induced myelopathy in a patient with tongue cancer: a case report. PMID- 22060136 TI - Phenolic compounds and antioxidant activity of olive leaf extracts. AB - The total phenolic content and antioxidant activities of olive leaf extracts were determined. Plant material was extracted with methanol and fractionated with solvents of increasing polarity, giving certain extracts. The qualitative changes in the composition of the extracts were determined after the storage of leaves for 22 h at 37 degrees C, before the extraction. Total polyphenol contents in extracts were determined by the Folin-Ciocalteu procedure. They were also analysed by liquid chromatography-mass spectrometry. Their antioxidant activities were evaluated using the diphenyl picrylhydrazyl method and the beta-carotene linoleate model assay. Moreover, the effects of different crude olive leaf extracts on the oxidative stability of sunflower oil at 40 degrees C and sunflower oil-in-water emulsions (10% o/w) at 37 degrees C, at a final concentration of crude extract 200 mg kg(-1) oil, were tested and compared with butylated hydroxyl toluene. PMID- 22060137 TI - Astrocyte elevated gene 1: biological functions and molecular mechanism in cancer and beyond. AB - Since its discovery, nearly one decade of research on astrocyte elevated gene 1 (AEG-1) has witnessed expanding knowledge of this molecule, ranging from its role in cancer biology to molecular mechanisms underlying the biological functions. As a multifunctional oncoprotein, AEG-1 has been shown to overexpress in multiple types of human cancer, and the elevation of AEG-1 in tumor cells leads to enhanced phenotypes characteristic of malignant aggressiveness, including increased abilities to proliferate robustly, to invade surrounding tissues, to migrate, to induce neovascularization, and to enhance chemoresistance. The multifunctional role of AEG-1 in tumor development and progression has been found to be associated with several signaling cascades, namely, 1) activation of NF kappa B, partially through direct interaction with p65; 2) PI3K/AKT signaling triggered by AEG-1 indirectly; 3) enhancement of the transcriptional activity of beta-catenin by indirect activation of MAPK and induction of LEF1; 4) regulation of mi/siRNA-mediated gene silencing by interacting with SND1; and 5) promotion of protective autophagy; in addition to possibly unknown mechanisms. Elevated AEG-1 expression is seen in nearly all tumor types, and in most cases AEG-1 positively correlates with tumor progression and poorer patient survival. Taken together, AEG-1 might represent a potential prognostic biomarker and therapeutic target. PMID- 22060139 TI - Structure-activity relationship studies of sulfonylpiperazine analogues as novel negative allosteric modulators of human neuronal nicotinic receptors. AB - Neuronal nicotinic receptors have been implicated in several diseases and disorders such as autism, Alzheimer's disease, Parkinson's disease, epilepsy, and various forms of addiction. To understand the role of nicotinic receptors in these conditions, it would be beneficial to have selective molecules that target specific nicotinic receptors in vitro and in vivo. Our laboratory has previously identified novel negative allosteric modulators of human alpha4beta2 (Halpha4beta2) and human alpha3beta4 (Halpha3beta4) nicotinic receptors. The effects of novel sulfonylpiperazine analogues that act as negative allosteric modulators on both Halpha4beta2 nAChRs and Halpha3beta4 nAChRs were investigated. This work, through structure-activity relationship (SAR) studies, describes the chemical features of these molecules that are important for both potency and selectivity on Halpha4beta2 nAChRs. PMID- 22060140 TI - Inhibition of 11beta-hydroxysteroid dehydrogenase 1 by carbenoxolone affects glucose homeostasis and obesity in db/db mice. AB - 1. One of the major causes of metabolic syndrome is elevated 11beta hydroxysteroid dehydrogenase 1 (11beta-HSD1) in the liver and adipose tissue. High 11beta-HSD1 expression contributes significantly to the diabetic phenotype in db/db mice. The purpose of the present study was to test the effect of the pharmacological inhibition of 11beta-HSD1 inhibition by carbenoxolone in db/db mice, a genetic model of diabetes. 2. Inhibition of 11beta-HSD1 by carbenoxolone was evaluated in liver homogenates obtained from untreated mice. At 0.4, 0.8, 1.6 and 3.2 MUmol/L, carbenoxolone reduced the conversion of cortisone to cortisol by 21%, 48%, 82% and 95%, respectively. 3. In another series of experiments in which female db/db mice were dosed orally with carbenoxolone (10, 25 and 50 mg/kg, twice daily) for 10 days, dose-dependent decreases were observed in 11beta-HSD1 activity in the brain, adipose and liver. In the case of 10 mg/kg carbenoxolone, the effects were not significant. In addition, the bodyweight of female db/db mice was reduced by 10% and 13% following treatment with 10 and 50 mg/kg carbenoxolone, respectively. Carbenoxolone treatment dose-dependently improved fat mass, energy expenditure, the serum lipid profile, serum leptin and insulin and glucose tolerance. Furthermore, 50 mg/kg carbenoxolone reduced both phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) activity in the liver by 75% and 52%, respectively. These decreases were associated with increased glucokinase protein expression and activity in the liver. 4. Carbenoxolone inhibition of 11beta-HSD1 in the liver, adipose and brain significantly improves the symptoms of metabolic syndrome in db/db mice. These improvements can be attributed to increased energy expenditure, decreased activity of the gluconeogenic enzymes PEPCK and G6Pase in the liver and improved glucokinase function in the liver and pancreas. PMID- 22060141 TI - Parafoveal processing of transposed-letter words and nonwords: evidence against parafoveal lexical activation. AB - The current experiments explored the parafoveal processing of transposed-letter (TL) neighbors by using an eye-movement-contingent boundary change paradigm. In Experiment 1 readers received a parafoveal preview of a target word (e.g., calm) that was either (1) identical to the target word (calm), (2) a TL-neighbor (clam), or (3) a substituted-letter (SL) nonword (chem). In Experiment 2 a further set of parafoveal preview conditions was explored including (4) an SL word condition (chum) and (5) a TL-nonword condition (caml). Across both experiments, readers' fixation durations on the target words were significantly longer when the previews were SL previews than when they were TL neighbors, suggesting that TL neighbors (when presented in the parafovea) facilitate processing rather than inhibit processing. Experiments 3 and 4 showed that this is in contrast to the inhibitory effects that are seen when TL neighbor previews appear in the fovea. PMID- 22060142 TI - The bivalency effect: evidence for flexible adjustment of cognitive control. AB - When bivalent stimuli (i.e., stimuli with features for two different tasks) appear occasionally, performance is slower on subsequent univalent stimuli. This "bivalency effect" reflects an adjustment of cognitive control arising from the more demanding context created by bivalent stimuli. So far, it has been investigated only on task switch trials, but not on task repetition trials. Here, we used a paradigm with predictable switches and repetitions on three tasks, with bivalent stimuli occasionally occurring on one task. In three experiments, we found a substantial bivalency effect for all trials with at least one source of conflict. However, this effect was reduced for the repetition trials sharing no features with bivalent stimuli, that is, for those without conflict. This confirms that the bivalency effect reflects an adjustment of cognitive control. The news is that this adjustment of cognitive control is sensitive to the presence of conflict, but neither to its amount nor to its source. PMID- 22060143 TI - The attentional blink is not affected by backward masking of T2, T2-mask SOA, or level of T2 impoverishment. AB - Identification of the second of two targets (T2) is impaired when presented shortly after the first (T1). This attentional blink (AB) is thought to arise from a delay in T2 processing during which T2 is vulnerable to masking. Conventional studies have measured T2 accuracy which is constrained by the 100% ceiling. We avoided this problem by using a dynamic threshold-tracking procedure that is inherently free from ceiling constraints. In two experiments we examined how AB magnitude is affected by three masking-related factors: (a) presence/absence of T2 mask, (b) T2-mask stimulus onset asynchrony (SOA), and (c) level of T2 impoverishment (signal-to-noise ratio [SNR]). In Experiment 1, overall accuracy decreased with T2-mask SOA. The magnitude of the AB, however, was invariant with SOA and with mask presence/absence. Experiment 2 further showed that the AB was invariant with T2 SNR. The relationship among mask presence/absence, SOA, and T2 SNR and the AB is encompassed in a qualitative model. PMID- 22060144 TI - Decomposing task-switching costs with the diffusion model. AB - In four experiments, task-switching processes were investigated with variants of the alternating runs paradigm and the explicit cueing paradigm. The classical diffusion model for binary decisions (Ratcliff, 1978) was used to dissociate different components of task-switching costs. Findings can be reconciled with the view that task-switching processes take place in successive phases as postulated by multiple-components models of task switching (e.g., Mayr & Kliegl, 2003; Ruthruff, Remington, & Johnston, 2001). At an earlier phase, task-set reconfiguration (Rogers & Monsell, 1995) or cue-encoding (Schneider & Logan, 2005) takes place, at a later phase, the response is selected in accord with constraints set in the first phase. Inertia effects (Allport, Styles, & Hsieh, 1994; Allport & Wylie, 2000) were shown to affect this later stage. Additionally, findings support the notion that response caution contributes to both global as well as to local switching costs when task switches are predictable. PMID- 22060145 TI - Unmixing the mixing cost: contributions from dimensional relevance and stimulus response suppression. AB - When participants repeat the same task in a context in which the task may also switch (a mixed block), performance deteriorates compared to when there is only one task repeating (a pure block). Three experiments were designed to assess how perceptual and motor transitions influenced this mixing cost. Experiment 1 provided three pure block baselines for perceptual and motor transitions. Experiments 2 and 3 examined these transitions in a mixed block. Results show that most of the mixing cost comes from two factors: (a) episodic interference in the mixed block when the stimulus changes and the response repeats, and (b) increased suppression in mixed blocks affecting trials where stimulus-response mappings repeat. We propose that these mechanisms are strategically applied when adopting a sustained "switching set" in mixed blocks. The purpose of this set would be to avoid perseveration errors in the most demanding trials (the task switching trials), but remaining active during task-repetitions. Results regarding the mixing cost are thus relevant to the assessment of models of task switching, which at present mainly rely on data from task switch trials. PMID- 22060146 TI - The role of gaze and road edge information during high-speed locomotion. AB - Robust control of skilled actions requires the flexible combination of multiple sources of information. Here we examined the role of gaze during high-speed locomotor steering and in particular the role of feedback from the visible road edges. Participants were required to maintain one of three lateral positions on the road when one or both edges were degraded (either by fading or removing them). Steering became increasingly impaired as road edge information was degraded, with gaze being predominantly directed toward the required road position. When either of the road edges were removed, we observed systematic shifts in steering and gaze direction dependent upon both the required road position and the visible edge. A second experiment required fixation on the road center or beyond the road edges. The results showed that the direction of gaze led to predictable steering biases, which increased as road edge information became degraded. A new steering model demonstrates that the direction of gaze and both road edges influence steering in a manner consistent with the flexible weighted combination of near road feedback information and prospective gaze information. PMID- 22060147 TI - Prediction of fluid losses from pork using subjective and objective paleness. AB - Meat paleness in pork Longissimus dorsi (LD) 1 day post-mortem (p-m) was measured subjectively using Japanese Pork Colour Scores (JPCS) and objectively using a Colormet fibre-optic (FO) meat probe (400-700 nm). Water-holding capacity (WHC), fluid loss during thin-slicing, and drip loss were measured in unfrozen and in frozen and thawed (FT) samples. FT caused a decrease in WHC, and an increase in slicing and drip loss (P < 0.001). FO interactance (i) was correlated (P < 0.01) with unfrozen WHC (R = 0.55), with FT WHC (r = -0.45 at 440 nm), with FT slicing loss (R = 0.81), with unfrozen drip loss (R = 0.66), and with FT drip loss (R = 0.61). Objective measurements proved that the development of pork paleness takes several days p-m and that paleness is increased by FT. Where fluid losses were predictable from paleness, the FO probe was superior to subjective evaluation by JPCS. PMID- 22060148 TI - Estimation of mutton carcass components using two predictors. AB - Carcass weight and the GR measurement (a measure of fatness) were used as predictors in models for estimating mutton carcass components. These parameters explained a moderate to large amount of the variation in component weights (r(2) = 0.47-0.93) except for trunk meat (of a 50% visual lean specification) with an r(2) = 0.15. The 557 carcasses used ranged in weight from 9.2 to 43.8 kg and in fat depth at the GR site from 0 to 41.0 mm. Analysis of the trunk meat components designated 50%, 80% and 90% visual lean showed that despite rigorous slicing the observed chemical lean percentage of the two former categories was less than expected. The application of the models for price setting of carcasses based on derived rather than nominal values is discussed. PMID- 22060149 TI - Definition of the optimum freezing rate-1. Investigation of structure and ultrastructure of beef M. longissimus dorsi frozen at different freezing rates. AB - The influence of freezing rate on location, shape and size of ice crystals formed during freezing of beef M. longissimus dorsi, as well as its influence on ultrastructure, were investigated. Muscle samples were frozen at different rates: 0.22 cm/h and 0.39 cm/h (cooling agent was chilled air), and 3.33 cm/h, 3.95 cm/h, 4.92 cm/h and 5.66 cm/h (cooling agent was liquid carbon dioxide which expanded in the sucking-pipe of the tunnel freezer). It was found that by slow freezing (freezing rates 0.22 cm/h and 0.39 cm/h) 30.00 MUm). An increase in the freezing rate was followed by a change in ice crystal location. In this case they had also been formed intracellularly. The number of crystals increased while their size decreased. The most intensive fibre damage was found in samples frozen at a rate of 0.22 cm/h, and the least in samples frozen at a rate of 3.95 cm/h with a freezing temperature of -50 degrees C. PMID- 22060150 TI - Definition of the optimal freezing rate-2. Investigation of the physico-chemical properties of beef M. longissimus dorsi frozen at different freezing rates. AB - The influence of freezing rate on weight loss during the freezing, thawing and cooking, on water-binding capacity, on sensory and other physico-chemical properties of beef M. longissimus dorsi was investigated. The changes in myofibrillar proteins in muscle samples frozen at different freezing rates were also investigated. The greatest weight losses during the freezing, thawing and cooking were registered at slow freezing procedures (freezing rate of 0.22 cm/h and 0.29 cm/h), when the meat was tougher and less soft. The solubility of myofibrillar proteins was least from those muscles frozen at such freezing rates. The freezing of samples at freezing rates of 3.33 cm/h and 3.95 cm/h had less influence on their physico-chemical characteristics. The solubility of the myofibrillar proteins from such samples was greatest, and the cooked samples were the most tender. From analysis of the results it was concluded that optimal conditions for meat freezing seem to be those when the average freezing rate is 2 5 cm/h. PMID- 22060151 TI - Post mortem evolution of myofilament spacing and extracellular space in veal muscle. AB - The post mortem evolution of water distribution was studied in muscle tissue from veal calves in two experiments. Myofilament spacing, extracellular space and rate and extent of pH fall were determined in Psoas major muscle in Experiment 1. Extracellular space and rate and extent of pH fall were determined in Longissimus dorsi, Psoas major and Trapezius muscles in Experiment 2. In Experiment 2, the variability of ultimate pH was increased by using adrenalin injections. The myofilament spacing decreased after slaughter when pH reached values around 5.9. In both experiments, the extracellular space began to increase soon after slaughter in close relation with the pH changes. The size of the ultimate extracellular space was significantly correlated with the rate of pH fall, but not with the ultimate pH. PMID- 22060152 TI - Use of polymerase chain reaction technology to detect a mutation associated with malignant hyperthermia in different pig tissues. AB - Refinements to a novel method to detect malignant hyperthermia in swine are described. Results show that the test can be performed on whole blood and that white blood cell isolation to generate template DNA is superfluous. Storage studies demonstrate that muscle samples are best utilized within 4 days if kept at 4 degrees C and that frozen storage at -20 degrees C is advised for longer periods. However freeze-thaw cycles should be avoided. Fat tissue was found to be much faster than other tissues to process, particularly to run the test on a large scale. MgCl(2) concentration and DNA polymerase source show small but non significant differences in polymerase chain reaction (PCR) product formation efficiency. An internal control is proposed in order to monitor endonuclease activity and to prevent partial digestions from being erroneously interpreted. In conclusion the test is very efficient in demonstrating the mutation associated with malignant hyperthermia. PMID- 22060153 TI - Quality attributes of major porcine muscles: A comparison with the Longissimus Lumborum. AB - Quality attributes of the longissimus lumborum (LL) were compared to the attributes of the muscles semimembranosus (SM), rectus femoris (RF), biceps femoris (BF), gluteus medius (GM) and the lateral portion of the semitendinosus (ST) in the ham, the psoas major (PM) in the loin and the supraspinatus (SS), infraspinatus (IS) and triceps brachii (TB) in the shoulder. Carcasses were allocated to quality groups based on measurements of muscle exudate and lightness (CIE-L(*)) in the LL. The SM, BF, GM and ST in the ham were similar to the LL (P > 0.05) in meat ultimate pH (pHu) and exudate and the GM, ST and LL were similar (P > 0.05) to the LL in lightness. The TB, RF, SS, PM and IS were similar (P > 0.05) in exudate, lightness and pHu and compared to the LL, were less exudative (P < 0.05) and darker (P < 0.05). When the LL was classed pale, and exudative, the GM, BF, SM and ST were also pale and exudative but the other muscles were darker and non-exudative. When the LL was classed dark and non-exudative, all other muscles were dark, non-exudative and the pHu was high. Therefore, the LL could serve as a reliable indicator of colour and exudate for all porcine musculature when the condition was dark and non-exudative (i.e. DFD). However, when the condition was pale and exudative (i.e. PSE), then the LL would serve as a reliable indicator only for the four major ham muscles, excluding the RF. PMID- 22060154 TI - Evaluation of halothane sensitivity and prediction of post-mortem muscle metabolism in pigs from a muscle biopsy using (31)P NMR spectroscopy. AB - Phosphorus nuclear magnetic resonance ((31)P NMR) measurements were made on biopsy samples from pig muscles. Two experiments were performed, one in France and one in Czechoslovakia. In experiment 1, the muscle samples were obtained by surgery from the Biceps femoris muscle of 10 pigs with various genetic types (5 Large White, 1 Large White * Landrace, 4 Pietrains). In experiment 2, the muscle samples were obtained by shot biopsy from the Longissimus dorsi muscle of 11 Belgian Landrace * Duroc pigs, of which 6 were halothane-negative and 5 halothane positive. The pigs were slaughtered by electrostunning and exsanguination respectively 3 weeks and 1 week after the biopsy, and meat quality traits (pH(1), reflectance and water holding capacity) were determined. The changes in adenosine triphosphate (ATP), creatine phosphate (CP), inorganic phosphate (P(i)) and pH, as deduced from NMR, were faster in Pietrains than in Large Whites, and in halothane-positive than in halothane-negative pigs. The value of the CP/P(i) ratio at 40 min after taking biopsy allowed discrimination between halothane positive and halothane-negative pigs. The values of pH, creatine phosphate and adenosine triphosphate, as measured at definite times on the biopsies, were correlated with the rate of post-mortem metabolism (r approx 0.8) and with meat quality traits. (31)P NMR measurements combined with a rapid and efficient biopsy technique appear as an alternative tool for assessment of both halothane sensitivity and prediction of meat quality in pigs. PMID- 22060155 TI - Carcass characteristics of Angus steers fed to Japanese market standards. AB - Japanese Black (Wagyu) cattle are characterized by an ability to consistently produce highly palatable, well-marbled beef. The Japanese utilize a unique management program which includes feeding the cattle a high roughage diet for extended periods of time, typically at least twice that of American feedlot practices. In this study, Angus steers were fed a typical US feedlot diet to the Japanese market endpoint of 680 kg. Carcasses were analyzed for marbling score, meat color and fat color by days on feed and adjusted to a common carcass weight. Results indicate that the quality traits studied did change (P < 0.05) with an increasing number of days on feed. The marbling score had a high standard error. PMID- 22060156 TI - The effect of spices and manganese on meat starter culture activity. AB - Three species, two proprietary spice blends and six starter preparations used in commercial salami manufacture were analysed for manganese and magnesium content. A mettwurst spices blend showed the highest levels of manganese (0.77 ppm expressed as effective product level assuming a 1% spice content) while mild and hot paprika and milano blend contained levels of manganese 1 4 - 1 3 lower. Magnesium levels for spices ranged from 3.14 to 25.81 ppm. Only two of the six meat starter cultures showed high levels of manganese (7.77 and 16.12 ppm as effective product level based on inoculation rate) while magnesium levels for all starter cultures did not exceed 0.37 ppm. The pH of salami products made with starter cultures containing no added manganese lagged behind that of products made with added mangenese (5 ppm) by 0.2 pH units at 48 h. The effect of manganese ions on the fermentation rate of starter bacteria was studied further in a salami model system, in the absence and presence of added spices. The mettwurst blend produced greatest stimulation and the milano the least. A level of 1.2 ppm of added manganese was sufficient to achieve an optimal (< 4.9 pH units within 48 h) fermentation in the presence of all five spices tested in the salami model system. PMID- 22060157 TI - A rapid method of oxymyoglobin purification. AB - Oxymyoglobin was isolated from bovine Longissimus lumborum muscle by precipitation with ammonium sulfate and purification in rapid conditions with only one chromatographic step on Mono-Q HR column with a HPLC system. Purity of oxymyoglobin was controlled by SDS-polyacrylamide gel electrophoresis and isoelectrofocusing. PMID- 22060158 TI - Inhibition of glutaminyl cyclase attenuates cell migration modulated by monocyte chemoattractant proteins. AB - QC (glutaminyl cyclase) catalyses the formation of N-terminal pGlu (pyroglutamate) in peptides and proteins. pGlu formation in chemoattractants may participate in the regulation of macrophage activation and migration. However, a clear molecular mechanism for the regulation is lacking. The present study examines the role of QC-mediated pGlu formation on MCPs (monocyte chemoattractant proteins) in inflammation. We demonstrated in vitro the pGlu formation on MCPs by QC using MS. A potent QC inhibitor, PBD150, significantly reduced the N-terminal uncyclized-MCP-stimulated monocyte migration, whereas pGlu-containing MCP-induced cell migration was unaffected. QC small interfering RNA revealed a similar inhibitory effect. Lastly, we demonstrated that inhibiting QC can attenuate cell migration by lipopolysaccharide. These results strongly suggest that QC-catalysed N-terminal pGlu formation of MCPs is required for monocyte migration and provide new insights into the role of QC in the inflammation process. Our results also suggest that QC could be a drug target for some inflammatory disorders. PMID- 22060159 TI - Attitudes towards massage modify effects of manual therapy in breast cancer survivors: a randomised clinical trial with crossover design. AB - Our aims were to investigate the immediate effect of myofascial release on heart rate variability and mood state, and the influence of attitude towards massage in breast cancer survivors with cancer-related fatigue. Twenty breast cancer survivors reporting moderate to high cancer-related fatigue participated in this crossover study. All patients presented to the laboratory at the same time of the day on two occasions separated by a 2-week interval. At each session, they received either a massage intervention or control intervention. Holter electrocardiogram recordings and Profile of Mood States questionnaire (six domains: tension-anxiety, depression-dejection, anger-hostility, vigour, fatigue, confusion) were obtained before and immediately after each intervention. The attitude towards massage scale was collected before the first session in all breast cancer survivors. The results showed a significant session * time interaction for standard deviation of the normal-to-normal interval (SDNN) (F= 5.063, P= 0.039), square root of mean squared differences of successive normal-to normal intervals (RMSSD) (F= 8.273, P= 0.010), high-frequency component (HF) (F= 7.571, P= 0.013), but not for index heart rate variability (F= 3.451, P= 0.080), low-frequency component (LF) (F= 0.014, P= 0.997) and ratio LF/HF (F= 3.680, P= 0.072): significant increases in SDNN, RMSSD and HF domain (P < 0.05) were observed after the manual therapy intervention, with no changes after placebo (P > 0.6). No influence of the attitude scale on heart rate variability results was found. A significant session * time interaction was also found for fatigue (F= 5.101, P= 0.036) and disturbance of mood (F= 6.690, P= 0.018) scales of the Profile of Mood States: patients showed a significant decrease in fatigue and disturbance of mood (P < 0.001) after manual therapy, with no changes after placebo (P > 0.50). A significant influence of the attitude scale was observed in tension-anxiety, depression-dejection and anger-hostility scales. This controlled trial suggests that massage leads to an immediate increase of heart rate variability and an improvement in mood in breast cancer survivors with cancer related fatigue. Further, the positive impact of massage on cancer-related fatigue is modulated by the attitude of the patient towards massage. PMID- 22060160 TI - Twenty-one years of prospective incidence of childhood type 1 diabetes in Hungary -the rising trend continues (or peaks and highlands?). AB - The aim of this study was to examine secular trends in the incidence of type 1 diabetes in children aged 0-14 yr in Hungary over the period 1989-2009. Newly diagnosed children with type 1 diabetes aged 0-14 yr in Hungary were prospectively registered from 1989 to 2009. Primary ascertainment of cases was by prospective registration using hospital notifications. Case ascertainment was over 96% complete using the capture-recapture method. Standardized incidence rates were calculated and secular trends estimated using Poisson regression analysis. In Hungary during 1989-2009 a total number of 3432 children were identified, giving a standardized incidence rate of 12.5 [95% confidence interval (CI) 12.1-12.9] per 100,000 person yr. The overall incidence rate has doubled from 7.7 (95% CI 6.4-9.15) per 100,000 per yr in 1989 to 18.2 (95% CI 15.7-20.9) per 100,000 per yr in 2009. A significant linear trend in incidence (p < 0.001) has been observed over time, with a mean annual increase of 4.4%. The increase in incidence was present in both genders and in all age groups, with the largest relative increase in the youngest age group (6.2%; p < 0.001). The incidence of type 1 diabetes in Hungarian children continues to increase, with the highest rate in the very young. Although it seems that transient periods of stabilization followed by increases in incidence are apparent, the long-term trend continues to be steadily upward. Incidence of childhood type 1 diabetes is a dynamic process, probably reflecting the changes of the environmental exposures and continued registration is necessary to recognize these trends. PMID- 22060161 TI - Welfare of calves - 1. Investigations into some aspects of calf slaughter. AB - The relationship between carotid occlusion, systemic blood pressure and brain function following electrical stunning and exsanguination (sticking) in slaughter calves (< 10 weeks) was assessed. Electrocorticograms, systemic blood pressure and evoked responses were measured in the chloralose. anaesthetised and the unanaesthetised states. Electrical stunning produced relatively short periods of measurable epilepsy in slaughter calves (18 s average). The pattern of decline in blood pressure after sticking showed variations between animals. However, the results indicated that two groups of animals could be recognised: a carotid occlusion (ballooning group) and no carotid occlusion (non-ballooning) group. The animals with ballooning (six out of 15 = 40%) developed occlusions of the caudal severed ends of the carotid arteries. These swellings, the so-called 'ballooning' effect, were characterised by large clots forming plugs at the severed ends of the arteries. When this phenomenon occurred the haemorrhaging was clearly impeded. This was reflected in the blood pressure traces which showed recovery episodes coinciding with the occurrence of the carotid occlusions. Our study indicates that in the worst possible case the development of a restriction to the outflow of blood can delay the rate of haemorrhaging and the decline in blood pressure. This can lead in turn to sustained brain function as evidenced by the continued presence of evoked responses following stun recovery and a long time to onset of the isoelectrical state in the electrocorticogram. PMID- 22060162 TI - Welfare of calves - 2. Increase in vertebral artery blood flow following exsanguination by neck sticking and evaluation of chest sticking as an alternative slaughter method. AB - The role of the vertebral arteries in delaying loss of sensibility following neck sticking in slaughter calves was investigated. Vertebral artery blood flow was measured using probes before, during and after electrical stunning and slaughter. Systemic blood pressure, electrocorticogram, visually evoked responses and the occurrence of carotid occlusions were also recorded. When carotid occlusion occurred, the time to onset of brain failure was delayed based on the development of an isoelectric state. In addition, when carotid occlusion occurred the mean arterial blood pressure was sustained for longer following slaughter, and concurrently vertebral artery blood flow could be maintained at about 30% of its initial level for up to 3 min. In some animals vertebral artery flow increased substantially following sticking. When chest sticking was used no occlusion of vessels occurred, mean arterial blood pressure fell promptly (within 8 s) and the onset of an isoelectric state did not extend beyond one minute. In addition, visually evoked responses were not present after 5 s following chest sticking. PMID- 22060163 TI - Post-natal changes in the biological characteristics of Semitendinosus muscle in male Limousin cattle. AB - Samples of semitendinosus muscle from 45 male Limousin cattle reared under similar conditions were taken at 1, 6 and 12 months of age (biopsy) and at 16 months (at slaughter). The development of biochemical (DNA, protein/DNA), enzymic (lactic dehydrogenase, isocitric dehydrogenase), and histochemical (ATPase, succunic dehydrogenase) characteristics was studied. Muscle fibres were classified according to their contractile and metabolic properties (SO = slow oxidative; FOG = fast oxidative glycolytic; FG = fast glycolytic). DNA accumulation or hyperplasia was observed up to the age of 16 months. The period of growth and development, between 1 and 12 months of age, was characterized by increased glycolytic metabolism, as evidenced by the conversion of FOG fibres into FG fibres, a decrease in ICDH activity and a rise in LDH activity. The period between 12 and 16 months, was characterized by a slowing down of the conversion of FOG fibres into FG fibres and an increase in ICDH activity. The presence of type IIC fibres at the four ages studied is discussed. Of the muscle characteristics studied, LDH activity seemed to be a discriminating factor between animals from an early age. It could thus be used as to predict animal muscle characteristics at birth. PMID- 22060164 TI - The value of carcass weight, fat depth measures and eye muscle area for predicting the percentage yield of saleable meat in Australian grass-fed beef carcasses for Japan. AB - The percentage saleable meat yield was determined for 42 carcasses from grass-fed steers representing a range of breed types purchased in Australia for the Japanese market. Their mean (s.d.) carcass weight and P8 fat depth were 329 (28.1) kg and 17.3 (4.3) mm, respectively. All measures of subcutaneous fat depth were significantly (P < 0.05) and moderately correlated with percentage saleable meat yield, with measures in the loin region showing a stronger association than those taken in the rump region. The association between P8 fat depth and the loin measures of subcutaneous fat were low and there was a significant (P < 0.05) association only between P8 and fat depth at the 10th rib (FD 10). The use of fat depth measurements from the loin region reduced the error associated with predicting saleable meat yield more than those from the rump region and significantly increased the amount of variation (R(2)) in saleable meat yield that was explained. Hot carcass weight (HCW) did not significantly (P > 0.05) improve prediction models when combined with subcutaneous fat depth measurements and overall, the R(2) values were low ranging from 0.19 to 0.42. The models indicated that fat depth measures and carcass weight are poor predictors of percentage meat yield in heavy-weight carcasses from mixed breed cattle as produced and processed in Australia. The prediction of percentage yield was in general significantly (P < 0.05) improved when measures of M. longissimus thoracis et lumborum (LD) area were added as independent variables to models based on hot carcass weight and subcutaneous fat depth measurements. With LD area added the amount of variation in yield that could be explained by the models increased by as much as 28%. Overall, the best model was based on fat depth at the 12th rib and LD area measured at the 5th rib for which the R(2) was 0.58 and the residual standard deviation was 1.63%. The next most accurate prediction of yield was provided by a model which included the independent variables used in the Australian Chiller Assessment Scheme namely HCW, FD10 and LD area at the 10th rib upon which breed type had no significant (P > 0.05) effect. PMID- 22060165 TI - Effects of pre-slaughter administration of antifreeze proteins on frozen meat quality. AB - The effects of pre-slaughter administration of antifreeze glycoproteins to lambs were assessed on lamb meat quality after thawing. Various concentrations of antifreeze glycoproteins (AFGP) from Antarctic Cod were injected intravenously into lambs (35 +/- 5 kg liveweight) at various times prior to slaughter. The lambs were electrically stunned, slaughtered, then subjected to high voltage electrical stimulation. The rate of glycolysis was assessed by monitoring the rate of pH fall and the ultimate pH. Longissimus dorsi muscles were removed from the carcasses 24 h post-slaughter. Samples were vacuum packed and stored frozen at -20 degrees C for 2-16 weeks. Upon thawing, samples were assessed for drip loss and sensory properties (foreign flavour, storage flavour, texture, tenderness, juiciness and overall acceptability). At certain times, frozen samples were examined by scanning electron microscopy after ice sublimation. Injection of AFGP had no effect on the rate of pH decline, and for all treatments the pH of samples was not significantly different. Injection of AFGP 10 min before slaughter had no effect at any of the concentrations of AFGP for any of the factors assessed, suggesting that 10 min was insufficient time for the AFGP to become associated with the muscle tissue. Injection of AFGP at either 1 or 24 h before slaughter reduced drip loss and ice crystal size. Crystals were smallest in the lambs injected to a final concentration of 0.01 MUg/kg AFGP, particularly when injected 24 h before slaughter. These results suggest that the addition of AFGP could reduce damage due to frozen storage of meat, if a cost-effective and consumer-acceptable method could be developed to incorporate these proteins into meat prior to freezing. PMID- 22060166 TI - Measurement of the components in meat patties by near infrared reflectance spectroscopy. AB - Near infrared calibrations have been derived and used routinely in the measurement of fat, moisture, protein, collagen free protein and starch in meat patties. The lower standard error of prediction (SEP) values for moisture, protein, fat and starch content determination were recorded with the first derivative calibration than with those of the second derivative treatment. The prediction for the moisture and protein content determinations with first derivative transforms were satisfactory, the correlation coefficients (r) being 0.99 and 0.98, respectively. Determining the fat content with both first and second derivative data showed excellent results, r amounting to more than 0.99. The result obtained for the starch and collagen free protein (CFP) content determination with the first derivative calibration, as well as with the second derivative treatment, showed a deviation from the chemical data and r was less than 0.97 in both cases. It is recommended that a sample preparation, such as demoisturizing or defatting, is needed to get a high correspondence with reference methods for starch and hydroxyproline determination in meat patties. PMID- 22060167 TI - Alteration of post-mortem ageing in beef by the addition of enzyme inhibitors and activators. AB - Twenty-four hours after stunning, slices of beef M. semitendinosus were soaked in buffers at 10 degrees C at different pH values containing enzyme inhibitors or calcium and magnesium salts and their enzyme levels and toughness determined up to 9 days. High pH meat was tender but appeared to have the same rate of ageing as meat of normal pH. Calcium chloride accelerated ageing and produced, after completion of conditioning, more tender meat than controls. In tenderising, sodium and potassium chlorides were 43% and MgCl(2) 73% as effective as Ca salts. Cysteine proteinase inhibitors were more effective in preventing ageing than serine or aspartate inhibitors. Cysteine and aspartate inhibitors together were the most effective in preventing ageing. The inhibition of ageing by cysteine inhibitors was overcome in the presence of 30 mM CaCl(2). The results suggest a main, but not exclusive, role for calpains in meat ageing and showed a synergistic non-enzymic tenderisation by the addition of high concentrations of salts. PMID- 22060168 TI - Dried sausages fermented with Staphylococcus xylosus at different temperatures and with different ingredient levels - Part I. Chemical and bacteriological data. AB - Sausages with added Staphylococcus xylosus were fermented at different temperatures and with different added levels of salt, glucose, nitrite, nitrate and Pediococcus pentosaceus in accordance with a six factor fractional design. The numbers of surviving Staphylococcus xylosus, lactic acid bacteria, pH, free fatty acids and residual amounts of nitrite and nitrate were measured. The effects of temperature and different ingredients on the chemical and bacterial data were tested using multiple linear regression and analysis of variance. The study showed that numbers of surviving Staphylococcus xylosus were reduced by high fermentation temperature, especially when salt concentration was low and glucose concentration high. High levels of nitrite and addition of Pediococcus pentosaceus had adverse effects as well. pH was lowered by high fermentation temperature, low salt concentration and addition of glucose and Pediococcus pentosaceus. On the other hand p H was increased by addition of nitrate. The pH lowering effect of glucose was small when temperature was low. The residual levels of nitrite and nitrate were increased by addition of nitrate, but then increased and decreased, respectively, by increasing temperature. Addition of glucose and Pedio coccus pentosaceus lowered the residual amount of nitrite. The level of free fatty acids was reduced by salt and increased by higher temperature. Of the individual acids, the amount of linoleic acid was also increased by addition of Pediococcus pentosaceus and decreased by nitrate. PMID- 22060169 TI - Dried sausages fermented with Staphylococcus xylosus at different temperatures and with different ingredient levels - Part II. Volatile components. AB - Sausages, with added Staphylococcus xylosus, were fermented at different temperatures and with different added levels of salt, glucose, nitrite, nitrate and Pediococcus pentosaceus in accordance with a six factor fractional design. The volatile compounds from the sausages were collected by dynamic headspace sampling and quantified and identified by gas chromatography and gas chromatography-mass spectrometry. The effects of temperature and different ingredients on the levels of individual volatiles were tested using multiple linear regression and analysis of variance. The study showed that sausages fermented under modern production conditions (high temperature, addition of glucose, nitrite, Pediococcus pentosaceus) in contrast to 'old-fashioned' sausages (added nitrate and fermented at low temperature) are likely to contain higher amounts of volatile acids, but lower levels of ethyl esters, certain short chain aldehydes as well as lipid autoxidation products. Several nitriles, nitro alkanes and one organic nitrate were identified for the first time in fermented sausages. Reaction mechanisms for those compounds and other classes of compounds are proposed and discussed in detail. PMID- 22060170 TI - Dried sausages fermented with Staphylococcus xylosus at different temperatures and with different ingredient levels - Part III. Sensory evaluation. AB - Sausages with added Staphylococcus xylosus were fermented at different temperatures and with different added levels of salt, glucose, nitrite, nitrate and Pediococcus pentosaceus in accordance with a six factor fractional design. The odour of the sausages was evaluated by a quantitative descriptive method with ten descriptors and by gas chromatography olfactometry. The sensory profile was correlated to the experimental design and the volatile compounds by partial least squares analysis. Also, the effects of temperature and different ingredients on the strength of the individual descriptors were tested using multiple linear regression and analysis of variance. The study showed that salami odour was more pronounced in sausages fermented at low temperature than in sausages fermented at high temperature and added nitrite, glucose and P. Pentosaceus. High temperature sausages had a more sour and cheesy aroma, but were less fatty and sourdough like. Salami odour was correlated with the presence of ethyl esters and 2 alkanones as well as with high numbers of Staphylococcus xylosus. 2- and 3 methylbutanal seemed to be influential as well. The sourish note to salami odour was especially caused by acetic and perhaps butanoic acid, the cheesy note by 2 methylpropionic, butanoic and 3-methylbutanoic acid. PMID- 22060171 TI - Comparative study of two classifications of muscle fibres: Consequences for the photometric determination of glycogen according to fibre type in red and white muscle of the pig. AB - The present experiment was designed to compare two classifications of myofibres in samples of muscles longissimus lumborum (LL) and semispinalis capitis (SC) taken at slaughter from 56 Large White pigs. Comparisons were made for the percentage and histological characteristics of the different types of myofibres and for the photometric determination of glycogen using periodic acid schiff (PAS) staining. Computerized image analysis was used (i) to classify the fibres on the basis of myosin ATPase activity [Brooke and Kaiser (1970) Arch. Neurol.23, 3669; types I, IIA and HB], or by combination of myosin ATPase and succino dehydrogenase (SDH) activities [Ashmore and Doerr (1971) Exp. Neurol.31, 408: types betaR, alphaR, and alphaW] and (ii) to compute the PAS staining luminance in individual fibres. Glycogen and related metabolites were determined in muscle homogenates using enzymatic techniques. The LL showed significantly higher glycogen and lactate contents than the SC and a significantly lower average PAS staining luminance (indicative of higher glycogen content). The LL was composed predominantly of fast-twitch (89%) and white (77.3%) fibres. The SC contained mainly red (61.1%) and fast-twitch (59.3%) fibres. In both muscles, the comparison of the two classifications indicates that all type I fibres showed high SDH activity and were therefore typed as betaR in Ashmore and Doerr's classification. However, in the LL, approximately 7% of the type IIB fibres showed a marked SDH activity and were thus typed as alphaR in Ashmore and Doerr's classification. Furthermore, significant differences were found between these two types for the cross sectional area of the fibres. In the SC, no significant differences were found for the pairwise comparisons of corresponding types between the two classifications. According to the photometric determination, fast twitch glycolytic fibres of the LL showed significantly higher glycogen content than red (fast- and slow-twitch) fibres, whereas in the SC, slow-twitch fibres had significantly lower glycogen levels than fast-twitch (red and white fibres). Corresponding types between the two classifications showed similar glycogen levels. PMID- 22060172 TI - Properties of nanocones formed on a surface of semiconductors by laser radiation: quantum confinement effect of electrons, phonons, and excitons. AB - On the basis of the analysis of experimental results, a two-stage mechanism of nanocones formation on the irradiated surface of semiconductors by Nd:YAG laser is proposed for elementary semiconductors and solid solutions, such as Si, Ge, SiGe, and CdZnTe. Properties observed are explained in the frame of quantum confinement effect. The first stage of the mechanism is characterized by the formation of a thin strained top layer, due to redistribution of point defects in temperature-gradient field induced by laser radiation. The second stage is characterized by mechanical plastic deformation of the stained top layer leading to arising of nanocones, due to selective laser absorption of the top layer. The nanocones formed on the irradiated surface of semiconductors by Nd:YAG laser possessing the properties of 1D graded bandgap have been found for Si, Ge, and SiGe as well, however QD structure in CdTe was observed. The model is confirmed by "blue shift" of bands in photoluminescence spectrum, "red shift" of longitudinal optical line in Raman back scattering spectrum of Ge crystal, appearance of Ge phase in SiGe solid solution after irradiation by the laser at intensity 20 MW/cm2, and non-monotonous dependence of Si crystal micro-hardness as function of the laser intensity. PMID- 22060174 TI - Mandatory ECG screening of athletes: is this question now resolved? AB - European and North American cardiologists have long debated the need for mandatory ECG screening of athletes in order to prevent sudden cardiac death. European investigators have recently adduced new evidence, which they believe supports the need for such screening. They note a decrease of sudden cardiac deaths among Italian athletes following the introduction of mandatory screening in that country, clearer definitions of resting ECG abnormalities in athletes, new and more encouraging calculations of cost/benefit ratios and direct comparisons of clinical examination alone against clinical examination plus ECG screening. Nevertheless, it seems that critical criteria for the success of any screening procedure (a substantial prevalence of the problem, coupled with an adequate test sensitivity and specificity) have yet to be satisfied. Very few athletes are liable to sudden cardiac death, only a few of those who are vulnerable will be identified by ECG screening, and even if all potential cases could be detected, restriction of their physical activity would be unlikely to have a major influence on their prognosis. At the same time, a requirement of mandatory testing would discourage engagement in physical activity, and would impose substantial direct costs on the community. Moreover, the large number of false positive test results could have important and undesirable consequences for both indirect medical costs and the overall health of competitors. ECG screening might become more effective if it could be focused on a smaller sub-group of vulnerable athletes, or if the problem of false positive tests could be addressed through an increase of test specificity. However, on the basis of current information, it would seem better to direct efforts in preventive medicine to more common causes of premature death in the young adult. PMID- 22060175 TI - Neural network modelling and dynamical system theory: are they relevant to study the governing dynamics of association football players? AB - Recent studies have explored the organization of player movements in team sports using a range of statistical tools. However, the factors that best explain the performance of association football teams remain elusive. Arguably, this is due to the high-dimensional behavioural outputs that illustrate the complex, evolving configurations typical of team games. According to dynamical system analysts, movement patterns in team sports exhibit nonlinear self-organizing features. Nonlinear processing tools (i.e. Artificial Neural Networks; ANNs) are becoming increasingly popular to investigate the coordination of participants in sports competitions. ANNs are well suited to describing high-dimensional data sets with nonlinear attributes, however, limited information concerning the processes required to apply ANNs exists. This review investigates the relative value of various ANN learning approaches used in sports performance analysis of team sports focusing on potential applications for association football. Sixty-two research sources were summarized and reviewed from electronic literature search engines such as SPORTDiscus, Google Scholar, IEEE Xplore, Scirus, ScienceDirect and Elsevier. Typical ANN learning algorithms can be adapted to perform pattern recognition and pattern classification. Particularly, dimensionality reduction by a Kohonen feature map (KFM) can compress chaotic high-dimensional datasets into low-dimensional relevant information. Such information would be useful for developing effective training drills that should enhance self-organizing coordination among players. We conclude that ANN-based qualitative analysis is a promising approach to understand the dynamical attributes of association football players. PMID- 22060176 TI - Assessing musculo-articular stiffness using free oscillations: theory, measurement and analysis. AB - Stiffness, the relationship between applied load and elastic deformation, is an important neuromechanical component related to muscular performance and injury risk. The free-oscillation technique is a popular method for stiffness assessment. There has been wide application of this technique assessing a variety of musculature, including the triceps surae, knee flexors, knee extensors and pectorals. The methodology involves the modelling of the system as a linear damped mass-spring system. The use of such a model has certain advantages and limitations that will be discussed within this review. Perhaps the major advantage of such a model is the specificity of the measure, whereby it is possible for the assessment conditions to simulate the type of loading witnessed during functional tasks and sporting situations. High levels of reliability and construct validity have typically been reported using such procedures. Despite these assurances of accuracy, a number of issues have also been identified. The literature reveals some concerns surrounding the use of a linear model for stiffness assessment. Further, procedural issues surrounding the administration of the perturbation, attention focus of the participant during the perturbation, signal collection, data processing and analysis, presentation of stiffness as a linear or torsional value, assessment load (single vs multiple vs maximal) and the stiffness-load relationship have been identified, and are all fundamentally related to the quality of the calculated output data. Finally, several important considerations for practitioners have been recommended to ensure the quality and consistency of stiffness data collection, processing and interpretation. PMID- 22060177 TI - Stability of haematological parameters and its relevance on the athlete's biological passport model. AB - The stability of haematological parameters is crucial to guarantee accurate and reliable data for implementing and interpreting the athlete's biological passport (ABP). In this model, the values of haemoglobin, reticulocytes and out-of-doping period (OFF)-score (Hb-60?Ret) are used to monitor the possible variations of those parameters, and also to compare the thresholds developed by the statistical model for the single athlete on the basis of its personal values and the variance of parameters in the modal group. Nevertheless, a critical review of the current scientific literature dealing with the stability of the haematological parameters included in the ABP programme, and which are used for evaluating the probability of anomalies in the athlete's profile, is currently lacking. In addition, we collected information from published studies, in order to supply a useful, practical and updated review to sports physicians and haematologists. There are some parameters that are highly stable, such as haemoglobin and erythrocytes (red blood cells [RBCs]), whereas others, (e.g. reticulocytes, mean RBC volume and haematocrit) appear less stable. Regardless of the methodology, the stability of haematological parameters is improved by sample refrigeration. The stability of all parameters is highly affected from high storage temperatures, whereas the stability of RBCs and haematocrit is affected by initial freezing followed by refrigeration. Transport and rotation of tubes do not substantially influence any haematological parameter except for reticulocytes. In all the studies we reviewed that used Sysmex instrumentation, which is recommended for ABP measurements, stability was shown for 72 hours at 4 degrees C for haemoglobin, RBCs and mean curpuscular haemoglobin concentration (MCHC); up to 48 hours for reticulocytes; and up to 24 hours for haematocrit. In one study, Sysmex instrumentation shows stability extended up to 72 hours at 4 degrees C for all the parameters. There are significant differences among methods and instruments: Siemens Advia shows lower stability than Sysmex as regards to reticulocytes. However, the limit of 36 hours from blood collection to analysis as recommended by ABP scientists is reasonable to guarantee analytical quality, when samples are transported at 4 degrees C and are accompanied by a certified steadiness of this temperature. There are some parameters that are highly stable, such as haemoglobin and RBCs; whereas others, such as reticulocytes, mean cell volume and haematocrit are more unstable. The stability of haematological parameters might be improved independently from the analytical methodology, by refrigeration of the specimens. PMID- 22060179 TI - Mechanistic studies of ethylene hydrophenylation catalyzed by bipyridyl Pt(II) complexes. AB - Cationic platinum(II) complexes [((t)bpy)Pt(Ph)(L)](+) [(t)bpy =4,4'-di-tert butyl-2,2'-bipyridyl; L = THF, NC(5)F(5), or NCMe] catalyze the hydrophenylation of ethylene to generate ethylbenzene and isomers of diethylbenzene. Using ethylene as the limiting reagent, an 89% yield of alkyl arene products is achieved after 4 h at 120 degrees C. Catalyst efficiency for ethylene hydrophenylation is diminished only slightly under aerobic conditions. Mechanistic studies support a reaction pathway that involves ethylene coordination to Pt(II), insertion of ethylene into the Pt-phenyl bond, and subsequent metal-mediated benzene C-H activation. Studies of stoichiometric benzene (C(6)H(6) or C(6)D(6)) C-H/C-D activation by [((t)bpy)Pt(Ph d(n))(THF)](+) (n = 0 or 5) indicate a k(H)/k(D) = 1.4(1), while comparative rates of ethylene hydrophenylation using C(6)H(6) and C(6)D(6) reveal k(H)/k(D) = 1.8(4) for the overall catalytic reaction. DFT calculations suggest that the transition state for benzene C-H activation is the highest energy species along the catalytic cycle. In CD(2)Cl(2), [((t)bpy)Pt(Ph)(THF)][BAr'(4)] [Ar' = 3,5 bis(trifluoromethyl)phenyl] reacts with ethylene to generate [((t)bpy)Pt(CH(2)CH(2)Ph)(eta(2)-C(2)H(4))][BAr'(4)] with k(obs) = 1.05(4) * 10( 3) s(-1) (23 degrees C, [C(2)H(4)] = 0.10(1) M). In the catalytic hydrophenylation of ethylene, substantial amounts of diethylbenzenes are produced, and experimental studies suggest that the selectivity for the monoalkylated arene is diminished due to a second aromatic C-H activation competing with ethylbenzene dissociation. PMID- 22060180 TI - C60 secondary ion Fourier transform ion cyclotron resonance mass spectrometry. AB - Secondary ion mass spectrometry (SIMS) has seen increased application for high spatial resolution chemical imaging of complex biological surfaces. The advent and commercial availability of cluster and polyatomic primary ion sources (e.g., Au and Bi cluster and buckminsterfullerene (C(60))) provide improved secondary ion yield and decreased fragmentation of surface species, thus improving accessibility of intact molecular ions for SIMS analysis. However, full exploitation of the advantages of these new primary ion sources has been limited, due to the use of low mass resolution mass spectrometers without tandem MS to enable enhanced structural identification capabilities. Similarly, high mass resolution and high mass measurement accuracy would greatly improve the chemical specificity of SIMS. Here we combine, for the first time, the advantages of a C(60) primary ion source with the ultrahigh mass resolving power and high mass measurement accuracy of Fourier transform ion cyclotron resonance mass spectrometry. Mass resolving power in excess of 100 000 (m/Deltam(50%)) is demonstrated, with a root-mean-square mass measurement accuracy below 1 part-per million. Imaging of mouse brain tissue at 40 MUm pixel size is shown. Tandem mass spectrometry of ions from biological tissue is demonstrated and molecular formulas were assigned for fragment ion identification. PMID- 22060178 TI - Antioxidant supplementation during exercise training: beneficial or detrimental? AB - High levels of reactive oxygen species (ROS) produced in skeletal muscle during exercise have been associated with muscle damage and impaired muscle function. Supporting endogenous defence systems with additional oral doses of antioxidants has received much attention as a noninvasive strategy to prevent or reduce oxidative stress, decrease muscle damage and improve exercise performance. Over 150 articles have been published on this topic, with almost all of these being small-scale, low-quality studies. The consistent finding is that antioxidant supplementation attenuates exercise-induced oxidative stress. However, any physiological implications of this have yet to be consistently demonstrated, with most studies reporting no effects on exercise-induced muscle damage and performance. Moreover, a growing body of evidence indicates detrimental effects of antioxidant supplementation on the health and performance benefits of exercise training. Indeed, although ROS are associated with harmful biological events, they are also essential to the development and optimal function of every cell. The aim of this review is to present and discuss 23 studies that have shown that antioxidant supplementation interferes with exercise training-induced adaptations. The main findings of these studies are that, in certain situations, loading the cell with high doses of antioxidants leads to a blunting of the positive effects of exercise training and interferes with important ROS-mediated physiological processes, such as vasodilation and insulin signalling. More research is needed to produce evidence-based guidelines regarding the use of antioxidant supplementation during exercise training. We recommend that an adequate intake of vitamins and minerals through a varied and balanced diet remains the best approach to maintain the optimal antioxidant status in exercising individuals. PMID- 22060181 TI - End-of-life care in the general wards of a Singaporean hospital: an Asian perspective. AB - BACKGROUND: Despite international differences in cultural perspectives on end-of life issues, little is known of the care for the dying in the general wards of acute hospitals in Asia. METHODS: We performed a retrospective medical chart review of all 683 adult patients who died without intensive care unit (ICU) admission in our Singaporean hospital in 2007. We first evaluated the prevalence of do-not-resuscitate (DNR) orders and orders for or against life-sustaining therapies; second, if such orders were discussed with the patients and/or family members; and third, the actual treatments provided before death. RESULTS: There were DNR orders for 66.2% of patients and neither commitment for DNR nor cardiopulmonary resuscitation (CPR) for 28.1%. Orders to limit life-sustaining therapies, including ICU admission, intubation, and vasopressors/inotropes were infrequent. Only 6.2% of the alert and conversant patients with DNR orders were involved in discussions on these orders. In contrast, such discussions with their family members occurred 82.9% of the time. Interventions in the last 24 hours of life included CPR (9.4%), intubation (6.4%), vasopressors/inotropes (14.8%), tube feeding (24.7%), and antibiotics (44.9%). Analgesia was provided in 29.1% of patients. CONCLUSIONS: There was a lack of commitment by doctors on orders for DNR/CPR and to limit life-sustaining therapies, infrequent discussions with patients on end-of-life decisions, and excessive burdensome interventions with inadequate palliative care for the dying. These findings may reflect certain Asian cultural biases. More work is required to improve our quality of end-of life care. PMID- 22060183 TI - Volatile organic compound adsorption on a nonporous silica surface: how do different probe molecules sense the same surface? AB - In this work, we compare experimental results to molecular simulation results of volatile organic compound (VOC) adsorption on nonporous silica. We adopted an effective model for the rough solid surface, obtained by a temperature annealing scheme, plus an experimental/simulation nitrogen adsorption tuning process over the silica energetic oxygen parameter. The measurement/prediction of selected VOCs, specifically, n-pentane and methylcyclohexane, is presented in terms of adsorption isotherms, with an emphasis on the angle distribution analysis of the three studied probe molecules with respect to the same modeled surface. PMID- 22060184 TI - Cellulosic biofuels and the road to energy security. PMID- 22060185 TI - Neuroprotection of paclitaxel against cerebral ischemia/reperfusion-induced brain injury through JNK3 signaling pathway. AB - In this study, we investigated the neuroprotective effects of paclitaxel in transient cerebral ischemia and possible regulatory mechanism of these neuroprotection. Our data showed that paclitaxel can down-regulate the increased MLK3, JNK3, c-Jun, Bcl-2, and caspase-3 phosphorylation induced by ischemia injury. Cresyl violet staining and immunohistochemistry results demonstrated that paclitaxel had neuroprotective effect against ischemia/reperfusion-induced neuronal cell death. These results indicated that paclitaxel has neuroprotection in ischemic injury through JNK3 signaling pathway and provided a novel possible drug in therapeutics of brain ischemia. PMID- 22060186 TI - Six-week consumption of a wild blueberry powder drink increases bifidobacteria in the human gut. AB - Wild blueberries are a rich source of polyphenols and other compounds that are highly metabolized by the intestinal microbiota and may, at the same time, affect the intestinal environment itself. A repeated-measure, crossover dietary intervention on human volunteers was designed to study the effect of six week consumption of a wild blueberry ( Vaccinium angustifolium ) drink, versus a placebo drink, in modulating the intestinal microbiota. Relative to total eubacteria, Bifidobacterium spp. significantly increased following blueberry treatment (P <= 0.05), while Lactobacillus acidophilus increased after both treatments (P <= 0.05). No significant differences were observed for Bacteroides spp., Prevotella spp., Enterococcus spp., and Clostridium coccoides . Bifidobacteria, which have been largely proposed to be of benefit for the host, appeared to be selectively favored suggesting an important role for the polyphenols and fiber present in wild blueberries. Results obtained suggest that regular consumption of a wild blueberry drink can positively modulate the composition of the intestinal microbiota. PMID- 22060187 TI - Production optimization of cyanophycinase ChpEal from Pseudomonas alcaligenes DIP1. AB - Pseudomonas alcaligenes DIP1 produces an extracellular cyanophycinase (CphEal). The corresponding gene (cphEal) was identified from subclones of a genomic DNA gene library by heterologously expressing the functionally active enzyme in Escherichia coli. The nucleotide sequence of the gene (1260 base pairs) was determined indicating a theoretical mass of 43.6 kDa (mature CphEal) plus a leader peptide of 2,6 kDa which corresponds well to the apparent molecular mass of 45 kDa as revealed by SDS-PAGE. The enzyme exhibited a high sequence identity of 91% with the extracellular cyanophycinase from P. anguilliseptica strain BI and carried an N-terminal Sec secretion signal peptide. Analysis of the amino acid sequence of cphE revealed a putative catalytic triad consisting of the serine motif GXSXG plus a histidine and a glutamate residue, suggesting a catalytic mechanism similar to serine-type proteases. The cyanophycinase (CphEal) was heterologously produced in two different E. coli strains (Top10 and BL21(DE3)) from two plasmid vectors (pBBR1MCS-4 and pET-23a(+)). The signal peptide of CphEal was cleaved in E. coli, suggesting active export of the protein at least to the periplasm. Substantial enzyme activity was also present in the culture supernatants. The extracellular cyanophycinase activities in E. coli were higher than activities in the wild type P. alcaligenes DIP1 in complex LB medium. Highest extracellular enzyme production was achieved with E. coli BL21(DE3) expressing CphEal from pBBR1MCS-4. Using M9 minimal medium was less effective, but the relatively low cost of mineral salt media makes these results important for the industrial-scale production of dipeptides from cyanophycin. PMID- 22060188 TI - Radiation induces up-regulation of somatostatin receptors 1, 2, and 5 in small cell lung cancer in vitro also at low absorbed doses. AB - BACKGROUND: Radiation can be used to up-regulate the expression of the somatostatin receptor (sstr) subtype 2 in small cell lung cancer (SCLC) cells at absorbed doses of 2-8 Gy. Increased sstr expression results in increased binding of radiolabeled somatostatin analogs to the tumor cell, which enhances the efficacy of systemic radionuclide therapy. The aim of this study was to determine if lower absorbed doses could up-regulate sstr2 expression, and possibly influence other sstr subtypes. METHODS: Human H69 SCLC cells were irradiated with an absorbed dose of 0.12-6.0 Gy and the sstr mRNA expression 3 days after irradiation was measured by quantitative real-time polymerase chain reaction for sstr1-5. At the same time point was the binding of [(177)Lu]-DOTA(0)-Tyr(3) octreotate to the cells measured after irradiation to an absorbed dose of 0.12 2.0 Gy and compared to the binding to nonirradiated cells. RESULTS: mRNA expression of sstr1, sstr2, and sstr5 was increased by a factor of 1.5-2 in cells irradiated with absorbed doses>=4 Gy and the binding of [(177)Lu]-DOTA(0)-Tyr(3) octreotate was, accordingly, 2-3 times higher to irradiated cells for all absorbed doses, except 0.25 Gy. CONCLUSION: The binding of [(177)Lu]-DOTA(0) Tyr(3)-octreotate was increased after radiation exposure. This increase was observed at low absorbed doses in parallel with up-regulation of sstr1, sstr2, and sstr5 mRNA. PMID- 22060189 TI - From retrospective assessment to prospective decisions in natural product isolation: HPLC-SPE-NMR analysis of Carthamus oxyacantha. AB - An extract of Carthamus oxyacantha (wild safflower) was investigated using two approaches: a traditional, nontarget fractionation by VLC and HPLC, and the hyphenated technique HPLC-PDA-HRMS-SPE-NMR followed by targeted isolation of selected constituents for inclusion in a screening library of pure natural products. While the nontarget fractionation involved considerable time spent on pursuing fractions containing well-known or undesired compounds, the hyphenated analysis was considerably faster and required less solvent and other consumables. The results were used to design and execute an optimized, HPLC-HRMS-guided, targeted isolation scheme aiming exclusively at a series of identified spiro compounds. Thus, HPLC-PDA-HRMS-SPE-NMR is a dereplication technique of choice, allowing economical acquisition of comprehensive data about compounds in crude extracts, which can be used for rational, prospective decisions about further isolation efforts. A total of 15 compounds were identified in the extract. Six spiro compounds, of which four have not previously been characterized, and tracheloside (a lignin glucoside) are presented with assigned 1H and 13C chemical shifts. PMID- 22060190 TI - Neuronal differentiation alters the ratio of Sp transcription factors recruited to the CYP46A1 promoter. AB - CYP46A1 is a neuron-specific cytochrome P450 that plays a pivotal role in maintaining cholesterol homeostasis in the CNS. However, the molecular mechanisms underlying human CYP46A1 expression are still poorly understood, partly because of the lack of a cellular model that expresses high levels of CYP46A1. Our previous studies demonstrated that specificity protein (Sp) transcription factors control CYP46A1 expression, and are probably responsible for cell-type specificity. Herein, we have differentiated Ntera2/cloneD1 cells into post mitotic neurons and identified for the first time a human cell model that expresses high levels of CYP46A1 mRNA. Our results show a decrease in Sp1 protein levels, concomitant with the increase in CYP46A1 mRNA levels. This decrease was correlated with changes in the ratio of Sp proteins associated to the CYP46A1 proximal promoter. To examine if the increase in (Sp3+Sp4)/Sp1 ratio was observed in other Sp-regulated promoters, we have selected four genes--reelin, glutamate receptor subunit zeta-1, glutamate receptor subunit epsilon-1 and MU-opioid receptor--known to be expressed in the human brain and analyzed the Sp proteins binding pattern to the promoter of these genes, in undifferentiated and differentiated Ntera2/cloneD1. Our data indicate that the dissociation of Sp1 from promoter regions is a common feature amongst Sp-regulated genes that are up regulated after neuronal differentiation. PMID- 22060191 TI - Choroideremia: effect of age on visual acuity in patients and female carriers. AB - BACKGROUND/AIMS: The extent and time course of vision loss in Choroideremia (CHM) is still unclear. We undertook this study to quantitate the change in visual acuity (VA) over time in order to gain a better understanding of the natural course of this retinal disorder. METHODS: Corrected VA of 120 males with CHM and 53 female carriers were collected from 24 studies and/or case reports published between 1981 and 2010, as well as from data on 15 patients examined at the Cole Eye Institute (Cleveland Clinic). Cross-sectional and longitudinal analyses were used to investigate the relationship between VA and age, as well as the progression rate of VA with age, respectively. Age grouping effects were investigated using ANOVA. RESULTS: The mean age of affected males was 36.6 +/- 17.7 years. The mean logMAR VA was 0.35 +/- 0.53. There was a significant 0.0072 decrease in logMAR VA per year (p = 1.22 * 10(-4)). There was a significant difference between VA of patients <50 years of age and those >50 years (0.27 +/- 0.39 vs. 0.61 +/- 0.81, p = 2.90 * 10(-5)). When we compared the rate of VA loss for patients <50 years vs. those >50 years, we also found a significant difference (0.01 +/- 0.04 vs. 0.06 +/- 0.08, p = 1.23 * 10(-2)). The average age of female carriers was 36.4 +/- 17.7 years, with an average logMAR VA of 0.36 +/- 0.6. There was no significant correlation between VA of female carriers and age (p = 0.12) with 46% of female carriers having a VA better than 20/20 at an average age of 33 years compared to 25% of affected males at 30 years. CONCLUSION: In affected males with CHM, VA decreases very slowly until subjects reach 50 years of age, at which time the rate and extent of vision loss become significantly higher. Additionally, VA decreases more rapidly as individuals get older. In contradistinction to affected males, VA loss in female carriers is much milder. PMID- 22060192 TI - Type 1 diabetes education and care: time for a rethink? PMID- 22060193 TI - Correlation of age at oral contraceptive pill start with age at breast cancer diagnosis. AB - Breast cancer is progressively diagnosed with increasing age. This study aimed to determine whether women who started using the oral contraceptive pill (OCP) at an early age developed breast cancer earlier than women who started using the OCP later in life. A database review of 1,010 breast cancer patients, who had used the OCP at some point in their life, was carried out. Associations of age at OCP start with age at breast cancer diagnosis were determined by multiple linear regression analysis, considering year of birth, year of diagnosis, age at first pregnancy, number of live births, age at menarche, and length of OCP use. There was evidence of a linear trend between age at OCP start and age at breast cancer diagnosis. Women who started using the OCP aged 18 years or younger were, on average, 4 years younger at breast cancer diagnosis than women who started using the OCP over the age of 30 years, and women who started using the OCP aged 22-25 years were, on average, 3 years younger (p-value for trend <0.001). The age when the OCP was started was positively associated with the age when breast cancer was first diagnosed. PMID- 22060194 TI - Phytochemical study of essential oil from the aerial parts of Coleus aromaticus Benth. AB - The essential oil composition of Coleus aromaticus Benth. (family Lamiaceae) was examined by capillary GC and GC-MS. Analyses revealed the presence of 28 constituents, of which 16 were identified. Thymol (83.39%) was found to be the major compound, while 1-octen-3-ol, terpine-4-ol, eugenol, trans-caryophyllene, caryophyllene oxide and alpha-cadinol were present as minor constituents. PMID- 22060195 TI - Dietary vitamin E supplementation and discoloration of pork bone and muscle following modified atmosphere packaging. AB - The effects of modified atmosphere (80% O(2): 20% CO(2)) and illumination on the discoloration rate of pork bone (lumbar vertebrae) and muscle (longissimus lumborum), and on muscle lipid stability were studied in vitamin E-supplemented and unsupplemented pigs. Bone-in pork chops were placed in 80% O(2): 20% CO(2) at 0 degrees C and stored for 5 days in the dark. The chops were then displayed under (a) fluorescent light in air or modified atmosphere or (b) in air with or without illumination. Lipid oxidation was increased by the modified atmosphere packaging but this detrimental effect was offset by vitamin E supplementation. Higher supplementation levels (198 and 207mg/kg) improved bone color stability regardless of the packaging atmosphere or the lighting conditions. Although vitamin E supplementation improved muscle color stability during display in air or modified atmosphere, the benefit of supplementation on muscle color was detectable only for illuminated storage. PMID- 22060196 TI - Levels of calpain and calpastatin in meat subjected to high pressure. AB - The levels of MU-, m-calpain and calpastatin were assayed in pressurized rabbit muscle. The crude calpain level from the pressurized muscle at 100 MPa was almost the same with that of control. Above 100 MPa, the level of calpain decreased rapidly with increased pressure. At 300 MPa, the calpain level was almost inactivated. When the crude extract was pressurized, the calpain level followed the same tendency as that in the pressurized muscle. When the extracts from control or pressurized muscle were subjected to DEAE-Sephacel column chromatography, MU- and m-calpains and calpastatin lost their activity with increasing pressure, but the degree of loss was different for each. Calpains resisted changes in pressurization at 200 MPa and were inactivated over 200 MPa. Inactivation of calpastatin at 100 MPa was faster than that of calpains. From the results, it was concluded that calpain levels remained in muscle pressurized up to 200 MPa, whereas calpastatin levels were decreased by the pressurization. Thus the total activities of calpains in pressurized muscle appear to have been increased by the pressure treatment and this may result in tenderization of meat. PMID- 22060197 TI - Effect of gamma radiation on levels of alpha-tocopherol in red meats and turkey. AB - The effect of low dose ionizing radiation on free alpha-tocopherol levels in beef, pork and lamb longissimus dorsi muscle and on turkey leg and breast muscle were determined. The samples were irradiated in air with a (137)Cs source at eight dose levels between 0 and 9.4 kGy at 5 degrees C. Irradiation resulted in a significant decrease in alpha-tocopherol levels in all of the meats studied. There were no statistically significant differences in the rate of loss of tocopherol due to species, with the exception of turkey breast. The rate of loss of tocopherol in turkey breast tissue was greater than the other meats. The information obtained in this study may be of use for 'chemiclearance' purposes since the relative effects due to species variation were examined. PMID- 22060198 TI - Ultrastructure of mechanically tenderised pork muscle. AB - Porcine biceps femoris muscles were mechanically tenderised by the use of a meat activator. The kind and degree of damage of muscle tissue were then examined under an electron microscope. It was observed that several changes, known from the studies of the post mortem muscles, were much more frequent in tenderised than in intact muscles. Additional changes were found as: disruption of the contractile system or its expansion till the A- and I-bands disconnected. Thus we suggest that mechanical tenderisation, by destroying several linkages between muscle fibres, between myofibrils and within myofibrils, may be responsible for lattice expansion and increase of brine uptake and overcoming the myofibrillar and connective tissue toughness of porcine meat. PMID- 22060199 TI - Determination of phospholipid content of intramuscular fat by Fourier Transform Infrared spectroscopy. AB - A method has been developed to determine the phospholipid content in fat extract with FTIR (Fourier Transform Infrared). l-alpha-Phosphatidylcholine from egg yolk in hexane solution was used as a reference for band identification at different concentrations. Phosphate bands were determined at different wavenumbers as described in the literature. A dilution series was made from meat extract and from 1-alpha-phosphatidylcholine. A linear calibration curve was obtained between the FTIR-results and the Iatroscan results, which were used as a reference. The band between 1282 cm(-1) and 1020 cm(-1) can be used for determination of phospholipid content. PMID- 22060200 TI - Impact of salt, phosphate and temperature on the effect of a transglutaminase (F XIIIa) on the texture of restructured meat. AB - The effect of the transglutaminase F XIIIa on texture parameters was analysed in meat model systems simulating a restructured meat product. Porcine M. longissimus dorsi at normal ultimate pH was obtained 2 days post mortem from pigs slaughtered at approx. 100 kg liveweight. The F XIIIa product used was a recombinant protein produced by fermentation of Saccharomyces cereviciae. In raw minced meat F XIIIa increased cohesion, hardness and elasticity when a time-temperature heat treatment of 37 degrees C and 90 min was used during processing, while processing at 10 degrees C for 23 h caused only minor texture changes. Salt and phosphate addition together with F XIIIa resulted in a remarkable increase in binding properties. Thus, the texture parameters increased particularly at salt levels between 2 and 4% and a phosphate level of 0.2%. Binding of meat pieces containing 0.2% phosphate, 1% salt and F XIIIa as 0.4% active enzyme to substrate showed significant effect on the tensile strength compared to the samples without F XIIIa, however, color deterioration of the product was observed when adding F XIIIa. PMID- 22060201 TI - Binding properties and colour of Bologna sausage made with varying fat levels, protein levels and cooking temperatures. AB - A little-studied procedure for adjusting the properties of low-fat products is to use the influence that both composition and certain processing factors exert on these properties. The object of the present work was to assess the effects of protein level (P, ranging from 10% to 16%), fat level (F, ranging from 10.1% to 22%) and cooking temperature (HT, ranging from 77 degrees C to 105 degrees C) on the binding properties and colour of meat emulsions. Protein content was the variable that most influenced total expressible fluid (TEF) and purge loss. Heating rate had scarcely any effect on the binding properties of Bologna sausages. Analysis of variance indicated that the regression models for parameters L, a and b were not significant. PMID- 22060202 TI - Presence of an unidentified myosin isoform in certain bovine foetal muscles. AB - Genetic variation in the establishment of bovine muscle fibre types was studied by comparing muscle differentiation at 210 days of foetal life in normal cattle and in 'culard' animals, which have muscular hypertrophy. The different fibre types were determined by histochemical and immunohistochemical analyses with monoclonal antibodies specific to different myosin heavy chain isoforms. The isoforms were separated by electrophoresis and quantified by the ELISA method. Four muscles with different contractile and metabolic characteristics were studied: Semitendinosus, Longissimus thoracis, Masseter (slow) and Cutaneus trunci (fast). Muscle fibres recognized by none of the antibodies used were observed in 'culard' foetuses in all the muscles studied and also in the Cutaneus trunci of normal animals. Electrophoretic analysis showed no particular myosin isoform in these muscles. It is possible therefore that the fibres contained a mysosin isoform until now unidentified in cattle, with a molecular weight the same as that of known isoforms. This newly observed isoform seems to be specific to muscles rich in IIB fibres such as Cutaneus trunci and to the muscles of adult 'culard' cattle. PMID- 22060203 TI - Modification of physico-chemical and colour parameters during the marketing of 'pate'. AB - The evolution of different physico-chemical parameters (iodine number, TBA test, residual nitrite level, pH and moisture) and CIE L (*)a (*)b (*) colour evolution, in pork liver 'pate', with and without sodium ascorbate addition, were studied. The samples were stored in an illuminated display cabinet at different lux intensities and in the dark. The regression equations were obtained for each one of the parameters under study, from the first day of exposure to light. The sodium ascorbate showed a protective effect on the photo-oxidation mechanism (measured by TBA test), but it did not have an influence on the samples in darkness. In both types of pate exposed to light, fading takes place and the most important variations in colour parameters are produced during the first 24 h of exposure to light. PMID- 22060204 TI - Effect of muscle type and food deprivation for 24 hours on the composition of the lipid fraction in muscles of Large White pigs. AB - The present study was designed to examine the lipid composition of a predominantly glycolytic (M. longissimus lumborum, LL) and a predominantly oxidative (M. semispinalis capitis, SC) muscle sampled at slaughter from Large White pigs fed or deprived of food for 24 h. The intramuscular lipid content was almost four-fold higher in the red SC than in the white LL. When expressed on a muscle tissue basis, the results indicated that the LL had significantly lower amount of tri-, di- and monoglycerides, free fatty acids, cholesterol and phospholipids than the SC. In both muscles, phosphatidylcholine represented the major constituent of the phospholipid fraction. The difference in phospholipid content between the LL and the SC was significant only for cardiolipin, phosphatidylethanolamine and phosphatidylinositol. When expressed on total lipid basis, the results showed that the SC contained significantly lower amount of phospholipids and higher amount of triglycerides than the LL, thus suggesting that the influence of muscle type on the content of intramuscular lipid was primarily due to a difference in the amount of triglycerides. Food deprivation for 24 h resulted in a significantly higher content of free fatty acids, as expressed on a muscle tissue basis, in both muscles. Relative to total lipid, food deprivation resulted in increased levels of free fatty acids and monoglycerides only in the LL. These results suggest that food deprivation for 24 h induced lipolysis in muscle, as evidenced by a modification in the relative composition of the neutral lipid fraction, but that this effect was muscle dependent. PMID- 22060205 TI - Estimation of the muscle to bone ratio of the bovine pelvic limb using a morphometric method. AB - Conformation is an indicator of carcass composition. The aim of this study was to derive an equation for estimating the composition of the bovine pelvic limb using morphometric variates. From a mixed group of 38 French bred bovines, the sample was chosen to have a wide range of conformation. The muscle to bone ratio (M B ) was used as an index of composition. The carcasses were weighed and the other variates of the equation were measured on carcass photographs: M B = 6.2 + 0.005W - 0.62EF AB + 12GH with W: carcass weight (kg); GH: medio-lateral diameter of the distal part of the leg (cm); EF AB : medio-lateral diameter of thigh (cm)/leg length(cm); (R(2) = 0.91 and rsd = 0.27). PMID- 22060206 TI - Characteristics of lamb carcasses of contrasting subjective muscularity. AB - In order to compare characteristics of lamb carcasses with superior muscularity (the European E class) with carcasses that did not fit the E specification, 114 E carcasses were individually matched for weight and fatness class with 114 Non-E carcasses. The carcasses (mean weight = 17 kg) were processed under commercial conditions into six trimmed, boneless cuts of the leg and saddle (inside, outside, knuckle, rump, striploin and tenderloin) and two bone-in cuts (hind shank and 7-rib rack). After adjustment for carcass weight, fatness (as assessed by fat depth C and tissue depth GR) and sex, the E-class group, relative to the Non-E group, had a 4.3% higher yield of leg and saddle cuts, a 14.2% higher leg muscularity index calculated from the weights of trimmed boneless cuts around the femur and femur length, a 13.6% higher muscle to bone ratio in the femur region, an 8.2% greater 'eye'-muscle depth (B), and a 3.7% greater 'eye'-muscle width (A) (all P < 0.001). All boneless cuts except the knuckle were heavier for the E group. Carcasses of female lambs had legs with higher muscle to bone ratios and a higher yield from the leg plus saddle (both P < 0.01), but the muscularity index was similar between sexes. It is concluded that although lamb carcasses subjectively selected as having higher muscularity will yield slightly more meat, this difference will be small compared with the greater muscle depth relative to bone length. The importance consumers attach to carcass or cut shape over and above any association with meat yield needs to be assessed. PMID- 22060208 TI - Structure and develoment of meat animals and poultry By H.G. Swatland. Published by Technomic Publishing Co Inc., Philadelphia, USA. 606 + xiii pp. 238 Swiss France (L118). PMID- 22060207 TI - Effect of electrical stimulation on post mortem biochemical characteristics and quality of Longissimus dorsi thoracis muscle from buffalo (Bubalus bubalis). AB - High voltage electrical stimulation (700 V, 1400 V peak, pulses 1 s on/1 s off, 60 Hz, 2 A) on buffalo carcasses resulted in a significantly more rapid pH fall in Longissimus dorsi thoracis muscle when compared to non stimulated controls (p < 0.01), during the first 24 h after slaughter. The IMP ATP ratio on the same period showed a much more rapid increase for the stimulated muscles (1.07 and 1.16 at times 1 and 2.5 hpost mortem vs control values of 0.77 and 0.83, respectively). Sensory and instrumental evaluation of texture of meat cooled by two distinct processes showed that tenderness at 24 hpost mortem was higher in the stimulated muscles compared to non-stimulated controls, irrespective of the cooling process adopted. High voltage stimulation significantly decreases cohesiveness, increases myofibril fragmentation; and SDS polyacrylamide gel electrophoresis of the myofibrillar proteins showed a weakening of Troponin T band during 6 days of ageing in non-stimulated control muscles, whereas electrical stimulation accelerated the process of ageing over 3 days. This is the first report on acceleration of conditioning in buffalo muscle and the conditions described here have a high potential for application in meat industry for buffalo slaughter. PMID- 22060209 TI - Investigation of methods to detect mechanically recovered meat in meat products - I: Chemical composition A. R. Crosland, R. L. S. Patterson, R. C. Higman, C. A. Stewart & K. D. Hargin (1995) Meat Science, 40(3), 289-302. PMID- 22060210 TI - Relationship of physically separable lean with chemical lean in pig carcasses E. Nagy, L. Kormendy, I.Elias, J.Czegledi-Janko & E.Zukal (1995) Meat Science, 40(1), 1-12. PMID- 22060211 TI - Comprehensive molecular analysis of Japanese patients with pediatric-onset MODY type diabetes mellitus. AB - BACKGROUND: In Asians, mutations in the known maturity-onset diabetes of the young (MODY) genes have been identified in only <15% of patients. These results were obtained mostly through studies on adult patients. OBJECTIVE: To investigate the molecular basis of Japanese patients with pediatric-onset MODY-type diabetes. SUBJECTS: Eighty Japanese patients with pediatric-onset MODY-type diabetes. METHODS: Mitochondrial 3243A>G mutation was first tested by the polymerase chain reaction restriction fragment length polymorphism analysis for maternally inherited families. Then, all coding exons and exon-intron boundaries of the HNF1A, HNF1B, GCK, and HNF4A genes were amplified from genomic DNA and directly sequenced. Multiplex ligation-dependent probe amplification analysis was also performed to detect whole-exon deletions. RESULTS: After excluding one patient with a mitochondrial 3243A>G, mutations were identified in 38 (48.1%) patients; 18 had GCK mutations, 11 had HNF1A mutations, 3 had HNF4A mutations, and 6 had HNF1B mutations. In patients aged <8 yr, mutations were detected mostly in GCK at a higher frequency (63.6%). In patients >9 yr of age, mutations were identified less frequently (45.1%), with HNF1A mutations being the most frequent. A large fraction of mutation-negative patients showed elevated homeostasis model assessment (HOMA) insulin-resistance and normal HOMA-beta indices. Most of the HNF1B mutations were large deletions, and, interestingly, renal cysts were undetectable in two patients with whole-gene deletion of HNF1B. CONCLUSION: In Japanese patients with pediatric-onset MODY-type diabetes, mutations in known genes were identified at a much higher frequency than previously reported for adult Asians. A fraction of mutation-negative patients presented with insulin resistance and normal insulin-secretory capacities resembling early-onset type 2 diabetes. PMID- 22060212 TI - Running in place: the challenge of prescribing medications today. PMID- 22060213 TI - From forgotten to mainstream: how a nurse-midwife's commitment to nitrous oxide changed practice. PMID- 22060214 TI - Regulation of prescriptive authority for certified nurse-midwives and certified midwives: a national overview. AB - INTRODUCTION: Certified nurse-midwives (CNMs) and certified midwives (CMs) provide primary care to women across the lifespan. Yet these primary care providers face barriers to practice that include restrictive state laws and regulations regarding prescriptive authority. The purpose of this review is to critically examine and report the regulatory requirements relative to prescriptive authority for CNMs/CMs in the United States. METHODS: State statutes and rules relative to midwifery practice were reviewed for all 50 United States and the District of Columbia. RESULTS: CNMs have been granted the authority to write prescriptions in all 50 United States and the District of Columbia, while CMs have been granted prescriptive authority only in the state of New York. Prescriptive authority for CNMs and CMs is regulated by individual state agencies and regulatory boards. Regulations regarding prescriptive authority for CNMs and CMs vary widely from state to state and are described, with a summary for each state presented. DISCUSSION: While CNMs are granted fully independent prescriptive authority in some states, the regulatory requirements relative to prescriptive authority for CNMs/CMs limit patients' access to necessary services in most states. PMID- 22060215 TI - Safety and risks of nitrous oxide labor analgesia: a review. AB - INTRODUCTION: This review of the safety and risks of nitrous oxide (N(2) O) labor analgesia presents results of a search for evidence of its effects on labor, the mother, the fetus, the neonate, breastfeeding, and maternal-infant bonding. Concerns about apoptotic damage to the brains of immature mammals exposed to high doses of N(2) O during late gestation, possible cardiovascular risks from hyperhomocysteinemia caused by N(2) O, a hypothesis that children exposed to N(2) O during birth are more likely to become addicted to amphetamine drugs as adults, and possible occupational risks for those who provide care to women using N(2) O/O(2) labor analgesia are discussed in detail. METHODS: Research relevant to the 4 special concerns and to the effects of N(2) O analgesia on labor and the mother child dyad were examined in depth. Three recent reviews of the biologic, toxicologic, anesthetic, analgesic, and anxiolytic effects of N(2) O; 3 reviews of the safety of 50% N(2) O/oxygen (O(2) ) in providing analgesia in a variety of health care settings; and a 2002 systematic review of N(2) O/O(2) labor analgesia were used. RESULTS: Nitrous oxide analgesia is safe for mothers, neonates, and those who care for women during childbirth if the N(2) O is delivered as a 50% blend with O(2) , is self-administered, and good occupational hygiene is practiced. Because of the strong correlation between dose and harm from exposure to N(2) O, concerns based on effects of long exposure to high anesthetic-level doses of N(2) O have only tenuous, hypothetical pertinence to the safety of N(2) O/O(2) labor analgesia. DISCUSSION: Nitrous oxide labor analgesia is safe for the mother, fetus, and neonate and can be made safe for caregivers. It is simple to administer, does not interfere with the release and function of endogenous oxytocin, and has no adverse effects on the normal physiology and progress of labor. PMID- 22060216 TI - Magnesium sulfate: past, present, and future. AB - First used anecdotally for the control of eclamptic seizures in the early 1900s, magnesium sulfate remains 1 of the most commonly used medications in obstetric practice today. Over the past 95 years, there have been countless research studies investigating the efficacy of magnesium sulfate for the management of eclampsia, preeclampsia, preterm labor, and most recently for prevention of cerebral palsy. The majority of this evidence undeniably supports the use of magnesium sulfate as the drug of choice for the prevention and treatment of eclampsia when evidence of severe disease is present. On the other hand, studies have not shown magnesium sulfate to be comparably more effective than other tocolytics for treating preterm labor, nor is there agreement on whether the evidence supports its use as a neuroprotective agent for prevention of cerebral palsy. The exact mechanism of action of magnesium sulfate remains largely hypothetical, and parenteral use has the potential to cause significant morbidity in high doses. This article reviews magnesium sulfate's remarkable history in obstetric practice and includes a summary of the evidence related to each of the controversies. An initial review of the physiology of magnesium sulfate is essential to understanding pharmacodynamic actions, dosing guidelines, and safety requirements. PMID- 22060217 TI - Bacterial vaginosis and preterm birth. AB - Although it has been clear for more than 2 decades that bacterial vaginosis increases the risk for preterm birth in some women, it is not yet fully understood why this association exists or how best to modify the risk. Incomplete understanding of this polymicrobial condition and difficulties in classification contribute to the challenge. The relationship between altered vaginal microflora and preterm birth is likely mediated by host immune responses. Because treatment of bacterial vaginosis during pregnancy does not improve preterm birth rates, and may in fact increase them, screening and treatment of asymptomatic pregnant women is discouraged. Symptomatic women should be treated for symptom relief. This article reviews the pathophysiology of bacterial vaginosis and controversy surrounding management during pregnancy. Agents currently recommended for treatment of this condition are reviewed. PMID- 22060218 TI - Omega-3 fatty acids and ginger in maternal health: pharmacology, efficacy, and safety. AB - Dietary supplements may be used by pregnant women if they perceive them to be natural and healthy products, if they are fearful of using prescription drugs, or if they are recommended by a health care provider. Usage surveys indicate that midwives feel comfortable in recommending some herbal products to their patients. There are sufficient data from randomized controlled trials on omega-3 fatty acids and ginger that their pharmacologic properties, efficacy, and safety data for specific indications in maternal health can be evaluated. Requests for information regarding these substances are likely to be encountered by health care providers who care for pregnant women. Omega-3 fatty acids benefit gestation, infant vision, and neurodevelopment, while effects on major depression in pregnancy and postpartum depression are less clear. Ginger is efficacious for nausea and vomiting in pregnancy but is limited in its safety data. Pharmacologic properties of each supplement and pathophysiology related to each indication are reviewed. It is recommended that pregnant and lactating women be advised to take an omega-3 fatty acid supplement daily, while the recommendation to use ginger is tentative and will likely be based on each practitioner's comfort level with the safety data that are presented. PMID- 22060219 TI - Antenatal corticosteroids at the beginning of the 21st century. AB - Corticosteroids administered to women in preterm labor are the standard of care for reducing neonatal morbidity and mortality associated with prematurity. These agents promote lung development and reduce the incidence of neonatal intraventricular hemorrhage. Several studies have investigated the method by which fetal lung fluid is cleared after birth. This exploration resulted in the elucidation of the Starling equation or the hypothesis that fluid filtration through capillary membranes is dependent on the balance between the pressure blood places on the capillary membranes and the osmotic pressure of the membranes. The clinical observation that a neonate experiences a vaginal squeeze during a vaginal birth may be important, but it can account for only a small percentage of the lung fluid absorbed. Perhaps more importantly, amiloride sensitive sodium transport channels (ENaCs) have emerged as key factors in the movement of alveolar fluid from the lung into the vascular system. Several potential clinical applications have been developed from this new knowledge about the physiology of lung fluid clearance at birth. Neonates born late preterm or at term by elective cesarean before the onset of labor are more likely to develop respiratory distress than those born vaginally. Based on the mechanism of action of antenatal corticosteroids, these drugs may be beneficial in the clearance of fetal lung fluid in this population. This article reviews how fetal lung fluid is cleared; the pharmacologic effects of corticosteroids on the fetus; and the risks, benefits, and controversies associated with corticosteroid use. PMID- 22060220 TI - United States medical eligibility criteria for contraceptive use 2010: a review of changes. AB - In the late 1990s, the World Health Organization (WHO) created the Medical Eligibility Criteria for Contraceptive Use (MEC), which provide evidence-based recommendations for safe and effective contraception in women with medical problems. The WHO MEC incorporate the best available evidence, are periodically updated, and are designed to be modified for specific populations. The US Centers for Disease Control and Prevention published US MEC in 2010. Changes to WHO guidelines for use in the US population include the following areas: breastfeeding, intrauterine device use, valvular heart disease, ovarian cancer, uterine fibroids, and venous thromboembolism. Medical conditions not covered by WHO recommendations but added to the US MEC include contraceptive guidance for women with inflammatory bowel disease, history of bariatric surgery, rheumatoid arthritis, endometrial hyperplasia, history of peripartum cardiomyopathy, and history of solid organ transplant. This article reviews the changes and additions to WHO MEC found in the US MEC. PMID- 22060221 TI - Strategies for partner management when treating sexually transmitted infection. AB - Chlamydia trachomatis and Neisseria gonorrhea are the most commonly reported bacterial sexually transmitted infections (STIs) in the United States, and reinfection accounts for 14% to 30% of all reported cases of these STIs. Treatment of both the woman and her partner is imperative to prevent long-term sequelae. This report examines the clinical course of a woman diagnosed with Chlamydia during pregnancy, and reviews various approaches to treating partners, including patient referral, provider referral, patient-delivered partner therapy, and accelerated partner therapy. PMID- 22060222 TI - Osteoporosis update. AB - INTRODUCTION: Osteoporosis is a chronic disease that is estimated to affect more than 75 million people worldwide. The US Department of Health and Human Services projects that the disease will impact more than 10 million women by 2020 if efforts to prevent it are ineffective. This article provides an overview of the pathophysiology of osteoporosis, prevention measures, and an update of the US Food and Drug Administration-approved medications that are used in the treatment of this widespread disease. METHODS: The current literature on the pathology, risks, and treatment of osteoporosis was reviewed. Studies providing the evidence for best practices are included in the following sections: prevention, diagnosis, and treatment of osteoporosis. Current national standards for diagnosis and treatment are highlighted. RESULTS: Bisphosphonates continue to be the most popular and widely used pharmacologic treatment for osteoporosis. However, when bisphosphonates are contraindicated or cause side effects so serious that it is not possible for some women to use them, alternative pharmacologic treatments and forms of dosing are available. DISCUSSION: When lifestyle and dietary modifications are insufficient to offset a diagnosis of osteoporosis, there are a variety of pharmaceutical options available that will provide safe and effective protection against fracture due to osteoporosis. PMID- 22060223 TI - Noncontraceptive uses of hormonal contraception. AB - Hormonal contraceptives are not only effective methods of birth control but also are effective at treating and/or preventing a variety of gynecologic and general disorders. Hormonal contraceptives can decrease the severity of acne, correct menstrual irregularities, treat endometriosis-associated pain, decrease bleeding associated with uterine myomas, decrease pain associated with menstrual periods, moderate symptoms associated with premenstrual syndrome, reduce menstrual migraine frequency, and increase bone mineral density as well as decrease the risk of specific cancers such as endometrial and ovarian cancer. Women need to receive this information to guide them in their decisions regarding choice of contraception as well as treatment options for gynecologic disorders. PMID- 22060224 TI - Counterfeit medications: impurities in the american drug supply. PMID- 22060225 TI - Current resources for evidence-based practice, November/December 2011. PMID- 22060226 TI - Calcium supplementation has cardiovascular risks for some women. PMID- 22060227 TI - Health care providers may not be following guidelines for human papillomavirus DNA testing. PMID- 22060228 TI - A high level of evidence supports care provided by certified nurse-midwives. PMID- 22060229 TI - Other literature of interest to midwives. PMID- 22060230 TI - Bacterial vaginosis. PMID- 22060232 TI - Non-medical prescribing: current and future contribution of pharmacists and nurses. PMID- 22060233 TI - Reporting natural health product related adverse drug reactions: is it the pharmacist's responsibility? AB - OBJECTIVES: Herbal medicines and other natural health products (NHPs) are sold in Canadian pharmacies as over-the-counter products, yet there is limited information on their safety and adverse effect profile. Signals of safety concerns associated with medicines can arise through analysis of reports of suspected adverse drug reactions (ADRs) submitted to national pharmacovigilance centres by health professionals, including pharmacists and the public. However, typically such systems experience substantial under-reporting for NHPs. The objective of this paper is to explore pharmacists' experiences with and responses to receiving or identifying reports of suspected ADRs associated with NHPs from pharmacy customers. METHODS: A qualitative study in which in-depth, semi structured interviews were conducted with 12 community pharmacists in Toronto, Canada. KEY FINDINGS: Pharmacists generally did not submit reports of adverse events associated with NHPs to the national ADR reporting system and cited several barriers, including lack of time, complexity of the reporting process and lack of knowledge about NHPs. Pharmacists who accepted responsibility for adverse event reporting appeared to have different perceptions of their professional role: they saw themselves as 'knowledge generators', contributing to overall healthcare knowledge. CONCLUSIONS: Reporting behaviour for suspected ADRs associated with NHPs may be explained by a pharmacist's perception of his/her professional role and perceptions of the relative importance of generating knowledge to share in the wider system of health care. PMID- 22060234 TI - Community pharmacy in the United Arab Emirates: characteristics and workforce issues. AB - OBJECTIVES: To determine the characteristics and workforce issues of community pharmacy practice in the United Arab Emirates (UAE). METHODS: Data collection was by anonymous cross-sectional survey. Questionnaires were distributed by hand to 700 community pharmacies to collect information about the participating pharmacists, pharmacy characteristics, the types of products and professional pharmacy services available to patients, and the barriers to offering professional services. KEY FINDINGS: A total of 344 pharmacists (49%) responded. Most were male (64%), had been in practice for less than 10 years (mean = 9.3, 95% confidence interval (CI) = 8.4-10.0) and were trained in India (35%) or Egypt (15%). The pharmacies were open for business 7 days/week (mean = 6.8, 95% CI = 6.7-8.8) with an average working day of 13 h (mean = 12.9, 95% CI = 12.7-13.2) and were mostly owned by independent non-pharmacists (70%). The pharmacies employed on average 2.6 full-time-equivalent (FTE) pharmacists (95% CI = 2.3-2.8) with 74% employing 1.8 FTE pharmacy assistants (95% CI = 1.7-2.0) and 47% employing trainee pharmacists (mean = 1.8 FTE, 95% CI = 1.6-2.0). Around three quarters of the pharmacies dispensed fewer than 100 prescriptions (75%) and responded to fewer than 100 requests for over-the-counter medicines (69%) per day. Most pharmacists encountered limited immediate access to up-to-date resources. CONCLUSIONS: This is the first study to explore the characteristics of community pharmacy practice in the UAE. The study provides baseline data which are critical to inform the development of strategies to improve the quality of community pharmacy services in the UAE. PMID- 22060235 TI - Patients' experience of hospital pharmaceutical services. AB - OBJECTIVE: This study aimed to investigate inpatients' and outpatients' need for information about medication, to what extent those needs were addressed and patient attitudes regarding pharmaceutical services. METHOD: Self-administered questionnaires were distributed to a sample of outpatients and inpatients in a UK district general hospital. Themes included satisfaction with information given about medication, potential confusion over medication prescribed by the general practitioner and by the hospital, access to a member of the pharmacy team and preferences on how information on medication should be given. KEY FINDINGS: Ninety-one outpatient and 126 inpatient questionnaires were available for analysis. All outpatients who responded acknowledged that they were told how long they might need to wait for their medicines to be dispensed, although approximately one-fifth felt they had to wait a long time. Nearly three-quarters of outpatients felt there was an opportunity to ask medication-related questions of the pharmacy team. Nearly three-quarters of inpatients reported they were encouraged to bring into any hospital any medication they were taking at home. Twenty-eight per cent of 95 inpatients reported that some of their existing medication was stopped while in hospital. For the inpatients who received information about new medication, this was explained to the patient verbally (76%) and both verbally and in writing (22%). Forty-two per cent of inpatients (and 36% of outpatients) expressed a preference to receive information about medication both verbally and in writing. Thirty-five (32%) of 110 inpatients were not aware that a pharmacy team had a presence on the ward. CONCLUSIONS: Overall the majority of both in- and outpatients appeared to be receiving appropriate pharmaceutical services. There is a need to raise the profile of the pharmacy team in regards to provision of medication advice for inpatients. Consideration needs to be given to better provision of written information about medication for patients. PMID- 22060236 TI - Sources of pre-admission medication information: observational study of accuracy and availability. AB - OBJECTIVE: To identify the accessibility of sources of pre-admission medication (PAM) information, to quantify agreement between the PAM list and the 'gold standard' PAM list (GS-PAML) and to categorise disagreements. METHODS: A random selection of patients with chronic illness admitted via accident and emergency to one of two study hospitals in the Republic of Ireland were recruited. For each patient, a GS-PAML was compiled and PAM lists were obtained from each relevant source, including patient own medications, general practitioner (GP) referral letter, past inpatient prescription (Kardex) and discharge summary, nursing home letter and personal communication with GP staff, community pharmacy staff and nursing home staff. Data were collected regarding availability for use of each source and allergy status. The GS-PAML was compared to each PAM, and disagreements were identified and categorised. KEY FINDINGS: Data were collected for 134 patients. Community pharmacy and nursing home staff were most accessible to researchers when undertaking the medication history (>90%), followed by GP staff (66%). Except for nursing home sources, agreement between PAML and GS-PAML was low (2-17% of patients, 44-77% of medications). The community pharmacy PAML most frequently agreed with the GS-PAML (17% of patients, 77% of medications) followed by GP staff (10% of patients, 69% of medications). Previous (within the last 6 months) discharge summaries (3% of patients, 49% of medications) and GP referral letters (2% of patients, 44% medications) agreed least frequently. Nursing home (100%) and GP (91%) staff provided most accurate allergy information. Drug omission (>35%) was the most common disagreement for all sources except nursing home staff. GP staff and community pharmacy PAMLs contained a considerable proportion of commission discrepancies. CONCLUSION: Community pharmacy and GP staff were identified as the most available and accurate sources of PAM information and should be prioritised when undertaking admission medication reconciliation in a busy clinical environment. PMID- 22060237 TI - Retrospective analysis of DATIX dispensing error reports from Scottish NHS hospitals. AB - AIM: The primary objective was to analyse reported dispensing errors, and contributing factors, in Scottish National Health Service hospitals by coding and quantifying error reports from the DATIX patient-safety software. The secondary objective was to gather managerial responses to dispensing error in order to gain a perspective on interventions already in place. METHODS: Incident reports collected from 23 Scottish hospitals over a 5-year period were analysed retrospectively. Reported incident types, contributory factors and managerial responses were categorised according to the event description, and the frequency of such factors calculated. KEY FINDINGS: Dispensing errors (n = 573), from both pharmacies and wards, were analysed. The main incident types were incorrect drug (19.2%, n = 110) and incorrect strength of drug (16.8%, n = 96). The main contributory factors were reported as drug name similarity (15.5%, n = 30) and busy wards/pharmacies (14.9%, n = 29). Patient-centred issues (6.1%, n = 12) also featured. Managerial responses to these errors took the form of meetings (16.7%, n = 42), increasing staff awareness (14.7%, n = 37) or staff reminders on the importance of checking procedures (17.9%, n = 45). CONCLUSIONS: The pattern of incidents reported is similar to previous research on the subject, but with a few key differences, such as, reports of errors associated with filling dosette boxes, and patient-centred issues. These differences indicate a potentially changing pattern of errors in response to new techniques in medicine management. Continued assessment of dispensing errors is required in order to develop practical interventions to improve medication safety. PMID- 22060238 TI - Factors affecting the views and attitudes of Scottish pharmacists to continuing professional development. AB - OBJECTIVES: To explore factors associated with Scottish pharmacists' views and attitudes to continuing professional development (CPD). METHODS: A retrospective principal component analysis of 552 (22.8%) questionnaires returned from a sample of 2420 Scottish pharmacists randomly selected from the 4300 pharmacists registered with the Royal Pharmaceutical Society of Great Britain and with a Scottish address. KEY FINDINGS: Principal component analysis of questionnaire items (n = 19) revealed four factors associated with Scottish pharmacists' views and attitudes to CPD: having positive support in the workplace, having access to resources and meeting learning needs, having confidence in the CPD process and motivation to participate in the CPD process. Community pharmacists were identified as the subgroup of pharmacists that needed most support for CPD regarding all four factors, while pharmacists working in primary care felt that they had most support in the workplace in comparison to other sectors (P < 0.05) and better access to resources and meeting learning needs when compared to community (P < 0.001) and hospital (P = 0.008) colleagues. Pharmacists working in primary care also felt more motivated to participate in the CPD process than those in the community (P < 0.001), and hospital pharmacists reported having more confidence in the CPD process compared to community pharmacists (P < 0.05). CONCLUSION: Using principal component analysis has identified four factors associated with Scottish pharmacists' views and attitudes to CPD. This may provide an approach to facilitate comparison of CPD views and attitudes with intra and inter professional groupings. Further study may allow identification of good practice and solutions to common CPD issues. PMID- 22060239 TI - Pharmacy professionalism and the digital age. AB - OBJECTIVES: To explore how the use of digital media could affect how people view professional behaviour. KEY FINDINGS: The growth in social networking sites has been phenomenal and they are now an extremely popular medium for interacting with others both commercially and privately. This as-yet-uncontrolled digital media provides ample opportunities for public and professional scrutiny for the unwary. Instances of employer screening and employee dismissal are already documented. All pharmacists who use digital media now need to be conscious that their virtual presence could be subject to regulator investigation. CONCLUSIONS: It is important that individuals are aware of the risks associated with using digital media and that pharmacy organisations begin to provide clear leadership to help pharmacists know what is and is not acceptable. PMID- 22060240 TI - Improving pharmacy counselling skills: an interdisciplinary model of support for students with English as an additional language. AB - OBJECTIVES: The pilot project, described in this paper, targeted English as an additional language (EAL) students to facilitate their development of patient counselling communication skills. METHODS: An interdisciplinary content-based model was developed drawing on an interactional sociolinguistic framework to map language use valued in pharmacy counselling. Evaluation included analysis of successive self-assessments and surveys of students, surveys of teaching staff and final test results. KEY FINDINGS: Evaluation indicated that the interdisciplinary model was highly successful in improving EAL students' competency in pharmacy counselling. CONCLUSIONS: The model may have possible wider application for education in health professional programmes. PMID- 22060241 TI - Implementation and faculty assessment of an oral examination in a therapeutics course in a distance synchronous education pharmacy programme. AB - OBJECTIVES: To describe the process and implementation of an oral exam in a large class with distance synchronous education technology and to evaluate the faculty's perspective of the development, administration, and assessment of the oral exam. METHODS: The Department of Pharmacy Practice at Nova Southeastern University, USA, created two patient cases for the oral exam per course over two semesters within the Therapeutics and Pathophysiology course sequence to be distributed across three campus sites. The faculty's perspective was evaluated utilizing a questionnaire distributed via an online survey. KEY FINDINGS: The oral exam was administered simultaneously across three campuses to a total of 464 students over two semesters. A total of 42 faculty members assisted in the exam process. Four cases were developed for the two exams, with detailed answer keys to minimize subjectivity in grading. Twenty-eight faculty members (66%) completed the assessment questionnaire. Most faculty were in support of continuing to administer the oral exam in subsequent therapeutic courses. CONCLUSIONS: Implementation of an oral exam in a large class with synchronous education via distance campuses is feasible. However, exam coordinators must take into account logistics such as time commitment from faculty, adequate facilities and detailed case and key development. PMID- 22060242 TI - Ellagic acid, a new antiglycating agent: its inhibition of Nepsilon (carboxymethyl)lysine. AB - Non-enzymatic glycation is a complex series of reactions between reducing sugars and amino groups of proteins. Accumulation of AGEs (advanced glycation end products) due to non-enzymatic glycation has been related to several diseases associated with aging and diabetes. The formation of AGEs is accelerated in hyperglycaemic conditions, which alters the structure and function of long-lived proteins, thereby contributing to long-term diabetic complications. The present study describes AGE inhibition and the mechanism of action of a new antiglycating agent, EA (ellagic acid), a flavonoid present in many dietary sources. Inhibition of AGE formation by EA was demonstrated with different proteins, namely eye lens TSP (total soluble protein), Hb (haemoglobin), lysozyme and BSA, using different glycating agents such as fructose, ribose and methylglyoxal by a set of complementary methods. These results suggest that the antiglycating action of EA seems to involve, apart from inhibition of a few fluorescent AGEs, predominantly inhibition of CEL [Nepsilon-(carboxyethyl)lysine] through scavenging of the dicarbonyl compounds. Furthermore, MALDI-TOF-MS (matrix-assisted laser-desorption ionisation-time-of-flight MS) analysis confirms inhibition of the formation of CEL on lysozyme on in vitro glycation by EA. Prevention of glycation-mediated beta-sheet formation in Hb and lysozyme by EA confirm its antiglycating ability. Inhibition of glycosylated Hb formation in human blood under ex vivo high-glucose conditions signifies the physiological antiglycating potential of EA. We have also determined the effectiveness of EA against loss of eye lens transparency through inhibition of AGEs in the lens organ culture system. These findings establish the antiglycating potential of EA and its in vivo utility in controlling AGE-mediated diabetic pathologies. PMID- 22060243 TI - Delay to celiac disease diagnosis and its implications for health-related quality of life. AB - BACKGROUND: To determine how the delay in diagnosing celiac disease (CD) has developed during recent decades and how this affects the burden of disease in terms of health-related quality of life (HRQoL), and also to consider differences with respect to sex and age. METHODS: In collaboration with the Swedish Society for Coeliacs, a questionnaire was sent to 1,560 randomly selected members, divided in equal-sized age- and sex strata, and 1,031 (66%) responded. HRQoL was measured with the EQ-5D descriptive system and was then translated to quality adjusted life year (QALY) scores. A general population survey was used as comparison. RESULTS: The mean delay to diagnosis from the first symptoms was 9.7 years, and from the first doctor visit it was 5.8 years. The delay has been reduced over time for some age groups, but is still quite long. The mean QALY score during the year prior to initiated treatment was 0.66; it improved after diagnosis and treatment to 0.86, and was then better than that of a general population (0.79). CONCLUSIONS: The delay from first symptoms to CD diagnosis is unacceptably long for many persons. Untreated CD results in poor HRQoL, which improves to the level of the general population if diagnosed and treated. By shortening the diagnostic delay it is possible to reduce this unnecessary burden of disease. Increased awareness of CD as a common health problem is needed, and active case finding should be intensified. Mass screening for CD might be an option in the future. PMID- 22060244 TI - Relationships between increasing outpatient encounters for neurological disorders and introductions of associated diagnostic codes, active duty military service members, 1998-2010. AB - Previous surveillance summaries of administrative data have indicated increases in the incidence and health care burdens of neurological disorders among active component U.S. military members during the last decade. Seventy-eight percent of the increase in average annual numbers of neurological disorders-related outpatient encounters during 2005-2010 is attributable to new diagnostic codes for three common conditions--sleep disorders, pain, and headache. The new codes were added to the International Classification of Diseases as "diseases of the nervous system" between 2005 and 2008. The pre-existing codes for these conditions are in most cases not classified as neurological. Visits for "organic sleep disorders" in particular represented nearly one-half of all outpatient encounters for neurological disorders in 2010. The use of the new diagnostic codes by healthcare providers can mask trends of the "true incidence" of illnesses and injuries and should be considered when interpreting surveillance analyses. PMID- 22060245 TI - Alcohol-related diagnoses, active component, U.S. Armed Forces, 2001-2010. AB - Alcohol abuse and dependence in the U.S. military are well-described public health problems. From 2001-2010, numbers and rates of incident alcohol-related diagnoses and alcohol-related medical encounters have increased among active component members, with the sharpest increases since 2007. Numbers of hospital bed days for acute alcohol diagnoses increased more than three-fold. Incidence rates of acute and chronic alcohol-related diagnoses were highest in 21-24-year old males in the Army, but among women rates were highest among those under 21. More than one-fifth (21%) of all acute alcohol-related encounters were recurrent diagnoses and the proportion of recurrences was higher among those in combat occupations (26%) and in the Air Force (35%). Recent increases in incident alcohol-related diagnoses may reflect increasing scrutiny of alcohol use among military members and a concomitant focus on referrals for evaluation of alcohol misuse. PMID- 22060246 TI - Update: cold weather injuries, U.S. Armed Forces, July 2006-June 2011. AB - From July 2010 through June 2011, the number of U.S. service members treated for cold injuries (n=557) was similar to recent prior years. The most frequently reported cold injury was hypothermia in the Marine Corps and frostbite in the other service branches. Cold injury rates were generally highest among service members who were less than 20 years old and of black, non-Hispanic race/ethnicity. Service members who train in wet and freezing conditions -- and their supervisors at all levels -- should know the signs of cold injury, ensure adequate hydration, and avoid tobacco, caffeine, and vasoconstrictive medications. PMID- 22060247 TI - Surveillance Snapshot: reportable medical events of heat injury in relation to heat index, June-September 2011. PMID- 22060248 TI - Internet-based treatment of depression: a randomized controlled trial comparing guided with unguided self-help. AB - Internet-delivered self-help for depression with therapist guidance has shown efficacy in several trials. Results from meta-analyses suggest that guidance is important and that self-help programs without support are less effective. However, there are no direct experimental comparisons between guided and unguided internet-based treatments for depression. The present study compared the benefits of a 10-week web-based unguided self-help treatment with the same intervention complemented with weekly therapist support via e-mail. A waiting-list control group was also included. Seventy-six individuals meeting the diagnostic criteria of major depression or dysthymia were randomly assigned to one of the three conditions. The Beck Depression Inventory (BDI-II) was used as the primary outcome measure. Secondary outcomes included general psychopathology, interpersonal problems, and quality of life. Sixty-nine participants (91%) completed the assessment at posttreatment and 59 (78%) at 6-month follow-up. Results showed significant symptom reductions in both treatment groups compared to the waiting-list control group. At posttreatment, between-group effect sizes on the BDI-II were d = .66 for unguided self-help versus waiting-list and d = 1.14 for guided self-help versus waiting-list controls. In the comparison of the two active treatments, small-to-moderate, but not statistically significant effects in favor of the guided condition were found on all measured dimensions. In both groups, treatment gains were maintained at 6-month follow-up. The findings provide evidence that internet-delivered treatments for depression can be effective whether support is added or not. However, all participants were interviewed in a structured diagnostic telephone interview before inclusion, which prohibits conclusions regarding unguided treatments that are without any human contact. PMID- 22060249 TI - Mindfulness and the attenuation of post-event processing in social phobia: an experimental investigation. AB - The present experimental study examined the ability of metacognitive strategies to reduce the distress associated with post-event processing (PEP). Individuals with DSM-IV generalized social phobia (N = 57) were randomly allocated to receive brief training in mindfulness, distraction, or no training (control group). Next, they underwent an experimental PEP induction. Following the induction, they were instructed to apply the metacognitive strategy (mindfulness or distraction) they were taught or to continue thinking about the social event the way they typically would following such an event (control). Participants rated their distress on a visual analogue scale prior to the PEP induction, and then every minute for 5 min while applying the metacognitive strategy. They also rated their affect immediately after applying the metacognitive strategy. Results suggest that mindfulness reduces distress significantly over the post-event period and results in significantly more positive affect than when receiving no training. In contrast, distraction does not reduce distress over the post-event period performs comparable to receiving no training. The results of this experimental investigation suggest that mindfulness has the potential to reduce distress associated with PEP and provide further support for the clinical utility of mindfulness in the treatment of generalized social phobia. PMID- 22060250 TI - Attention modification in persons with fibromyalgia: a double blind, randomized clinical trial. AB - Contemporary models of chronic musculoskeletal pain emphasize the critical roles of fear, anxiety, and avoidance as well as biases in attention in the development and maintenance of chronic pain disability. Evidence supports the influence of individual difference variables such as anxiety sensitivity, pain-related anxiety, and catastrophizing on the pain experience and on pain-related attentional biases. Changes in attentional biases have been associated with treatment gains in patients with clinically significant anxiety. The Attentional Modification Paradigm (AMP) is a modification of the dot-probe paradigm used to facilitate such changes in attentional biases. Given the relationship between chronic musculoskeletal pain and anxiety, AMP may be effective in reducing pain as well. Participants included persons (n = 17) with fibromyalgia and were randomly assigned to either an AMP condition or a control condition. The participants completed two 15-minute AMP sessions per week for 4 weeks. Those in the AMP condition reported statistically significant and substantial reductions on several individual difference variables relative to those in the control condition, and a greater proportion experienced clinically significant reductions in pain. These preliminary results offer a promising new avenue for treating chronic musculoskeletal pain that warrants additional research. Comprehensive results, limitations, and future directions are discussed. PMID- 22060255 TI - Predictors of recovery from prenatal depressive symptoms from pregnancy through postpartum. AB - BACKGROUND: Identifying predictors of the course of depressive symptoms from pregnancy through postpartum is important to inform clinical interventions. METHODS: This longitudinal study investigated predictors of recovery from prenatal elevated depressive symptoms in the postpartum period. Forty-one pregnant women completed demographic, interpersonal, and psychosocial self-report assessment measures at 32 weeks of gestation and again 12 weeks postpartum. RESULTS: Of those with elevated depressive symptoms, defined as a Beck Depression Inventory-II (BDI-II) score >=10, at the prenatal baseline, 39% (n=16) recovered to nonelevated symptom levels postpartum, whereas 61% (n=25) experienced sustained elevated symptoms. Women who recovered evidenced significantly lower baseline depression severity and more frequent engagement in physical activity and cohabitated with a romantic partner. In multiparous women (n=25), history of past postpartum depression (PPD) differentiated between those with transient and those with persisting symptoms, although history of lifetime depression did not. None of the additional demographic, interpersonal, or psychosocial variables investigated differentiated between groups. Logistic regression analysis showed prenatal depression severity and exercise frequency as predictors of recovery postpartum. CONCLUSIONS: Results suggest most women will not experience spontaneous recovery. Women with prenatal heightened symptom severity and previous experiences with PPD are acutely vulnerable to experience sustained symptoms. In contrast, having a cohabitating partner and engagement in prenatal exercise predicted symptom improvement. Physical exercise may be an important clinical recommendation, as it may improve mood. Given the small sample size, these results are preliminary. Implications and future research recommendations are discussed. PMID- 22060256 TI - Depressive symptoms and health-related quality of life in breast cancer survivors. AB - BACKGROUND: Breast cancer diagnosis and treatment can have a profound influence on a woman's physical, psychosocial, and overall well-being. We examined the prevalence of depressive symptoms and its association with health-related quality of life (HRQOL) in women who are survivors of breast cancer. We also assessed if factors, including metastasis, cancer recurrence, diagnosis of new primary cancers, and comorbid conditions, are associated with depressive symptoms. METHODS: The Patient Health Questionnaire (PHQ-8) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were mailed to assess depressive symptoms and HRQOL, respectively, in breast cancer patients who received cancer treatment in a large tertiary cancer center. RESULTS: Two hundred forty patients participated (56% response rate and 6-13 years since treatment). The mean score on the PHQ-8 scale was 4 points (standard deviation [SD] 4.8, median 2.0). Sixteen percent had PHQ-8 score >=10 and were categorized as depressed. Depression was inversely associated with HRQOL subscales for functioning, financial, and global health and positively associated with symptoms. Logistic regression showed that younger age (odds ratio [OR] age in years 0.92, 95% confidence interval [CI] 0.86- 0.99, p<0.02), rheumatoid arthritis (OR 8.4, 95%CI 1.3-57.4, p<0.03), and years from treatment (OR 0.70, 95% CI 0.46-0.99, p<0.05) were significant correlates of depression. CONCLUSIONS: Depression is a significant health concern for breast cancer survivors and is associated with lower HRQOL. The results suggest the need to monitor women with breast cancer for depression and provide resources for treating depression during the survival period. PMID- 22060257 TI - A study on the effect of different chemical routes on functionalization of MWCNTs by various groups (-COOH, -SO3H, -PO3H2). AB - Pristine multiwall carbon nanotubes [MWCNTs] have been functionalized with various groups (-COOH, -SO3H, -PO3H2) using different single- and double-step chemical routes. Various chemical treatments were given to MWCNTs using hydrochloric, nitric, phosphoric, and sulphuric acids, followed by a microwave treatment. The effect of the various chemical treatments and the dispersion using a surfactant via ultrasonication on the functionalization of MWCNTs has been studied. The results obtained have been compared with pristine MWCNTs. Scanning electron microscopy, energy dispersive X-ray [EDX] spectroscopy, and transmission electron microscopy confirm the dispersion and functionalization of MWCNTs. Their extent of functionalization with -SO3H and -PO3H2 groups from the EDX spectra has been observed to be higher for the samples functionalized with a double-step chemical route and a single-step chemical route, respectively. The ID/IG ratio calculated from Raman data shows a maximum defect concentration for the sample functionalized with the single-step chemical treatment using nitric acid. The dispersion of MWCNTs with the surfactant, Triton X-100, via ultrasonication helps in their unbundling, but the extent of functionalization mainly depends on the chemical route followed for their treatment. The functionalized carbon nanotubes can be used in proton conducting membranes for fuel cells. PMID- 22060259 TI - Quartz crystal impedance response of nonhomogenous composite electrodes in contact with liquids. AB - A new model of quartz-crystal impedance (QCI) of nonuniform layers composed of bumps of carbon particles (either porous or nonporous) and a polymeric binder layer has been proposed. The solid particles are modeled by semispherical and oblate semispheroid bumps embedded into the "sea" of a polymeric binder layer. On the basis of this model and elaborating on the principles of hydrodynamic spectroscopy of composite electrode materials, the geometric and porous structure parameters of nanoporous carbon and nonporous graphite composite electrodes in contact with liquids have been reliably determined. This work is believed to create a solid theoretical background for both advanced studies and optimized formulations of the composite electrodes suited to practical electrochemical devices and for the interpretation of the processes of ions and solvent insertion into nanoporous carbon electrodes uniquely probed by the QCI method (supercapacitive cells, desalination membranes). PMID- 22060260 TI - Molecular ordering of ethanol at the calcite surface. AB - To produce biominerals, such as shells, bones, and teeth, living beings create organic compounds that control the growth of the solid phase. Investigating the atomic scale behavior of individual functional groups at the mineral-fluid interface provides fundamental information that is useful for constructing accurate predictive models for natural systems. Previous investigations of the activity of coccolith-associated polysaccharides (CAP) on calcite, using atomic force microscopy (AFM) [Henriksen, K., Young, J. R., Bown, P. R., and Stipp, S. L. S. Palentology 2004, 43 (Part 3), 725-743] and molecular dynamics (MD) modeling [Yang, M., Stipp, S. L. S., and Harding, J. H. Cryst. Growth Des. 2008, 8 (11), 4066-4074], have suggested that OH functional groups control polysaccharide attachment. The purpose of this work was to characterize, using X ray reflectivity (XR) combined with molecular dynamics (MD) simulations, the structuring on calcite of a layer of the simplest carbon chain molecule that contains an OH group, ethanol (CH(3)-CH(2)-OH). We found evidence that EtOH forms a highly ordered structure at the calcite surface, where the first layer molecules bond with calcite. The ethanol molecules stand up perpendicularly at the interface or nearly so. As a consequence, the fatty, CH(3) ends form a new surface, about 6 A from the termination of the bulk calcite, and beyond that, there is a thin gap where ethanol density is low. Following is a more disordered layer that is two to three ethanol molecules thick, about 14 A, where density more resembles that of bulk liquid ethanol. The good agreement between theory and experiment gives confidence that a theoretical approach can offer information about behavior in more complex systems. PMID- 22060261 TI - The virtue of temperance: built-in negative regulators of quorum sensing in Pseudomonas. AB - Many bacteria are now believed to produce small signal molecules in order to communicate in a process called quorum sensing (QS), which mediates cooperative traits and a co-ordinated behaviour. Pseudomonads have been extensively studied for their QS response highlighting that it plays a major role in determining their lifestyle. The main QS signal molecules produced by Pseudomonas belong to the family of N-acyl-homoserine lactones (AHLs); these are synthesized by a LuxI family synthase and sensed by a LuxR-family regulator. Most often in Pseudomonas, repressor genes intergenically located between luxI and luxR form an integral part of QS system. Recent studies have highlighted an important role of these repressors (called RsaL and RsaM) in containing the QS response within cost effective levels; this is central for pseudomonads as they have very versatile genomes allowing them to live in constantly changing and highly dynamic environments. This review focuses on the role played by RsaL and RsaM repressors and discusses the important implications of this control of the QS response. PMID- 22060262 TI - Effects of fibrates on C-reactive protein concentrations: a meta-analysis of randomized controlled trials. AB - BACKGROUND: The effects of fibrates on C-reactive protein (CRP) are controversial. This meta-analysis was conducted to synthesize the available clinical trial evidence and summarize the effects of fibrates on CRP concentrations. In addition, this study assessed the relationship between changes in CRP and lipid measures. METHODS: A systematic search was conducted of randomized controlled trials on the effects of fibrates on CRP concentrations in the PubMed, Embase and Cochrane Library Database up to January 2011. A meta analysis was performed using a random effect model. Meta-regression analysis was employed to assess the relationships between average change in CRP and lipid profiles. RESULTS: Sixteen randomized controlled trials were included in the meta analysis. Compared with placebo, treatment with fibrates significantly decreased CRP concentrations (weighted mean difference -0.47 mg/L, 95% confidence interval 0.93 to -0.01 mg/L, p=0.046). Fibrates significantly reduced CRP concentrations in trials with a higher baseline CRP concentrations (>= 3 mg/L). There was a significant correlation between change in CRP and change in high-density lipoprotein cholesterol (regression coefficient or slope=-2.03, 95% CI -3.20 to 0.87, p=0.001). CONCLUSIONS: Fibrates can reduce CRP concentrations and change in CRP was correlated with change in high-density lipoprotein cholesterol but not with triglyceride. These findings suggest that patients with dyslipidemia could benefit from fibrates treatment by CRP lowering and this benefit is associated with lipid profile improving. PMID- 22060263 TI - Cold induced toughening in excised pork as affected by pH, R value and time at boning. AB - Porcine M. longissimus dorsi from paired sides of 87 carcasses representing a wide range of post-mortem glycolic rates were obtained to study the cold toughening potential in early excised cuts (right sides) as compared to a conventional, cold boning procedure (left sides). The pH, R value and time at boning were measured and evaluated for their effect on tenderness. The early excised cuts were chilled by two different chilling rates: fast chilling in ice water or chilling by air at 2-4 degrees C in a conventional chilling room. The cold toughening potential for excised fast chilled cuts was significantly (P < 0.001) affected by pH, R value and time at boning, the latter parameters however being significantly correlated (P < 0.001). From partial regression analysis, the R value appeared to be the main factor involved in tenderness variations. Thus the R value as measured at time of boning was found to be the parameter showing the highest predictive value for estimating the risk of cold toughening in early excised cuts. When early excised cuts were chilled in air at 2-4 degrees C, the results from the present study showed tenderness levels comparable to the conventional cold boning procedure, irrespective of pH, R value and time at boning. PMID- 22060264 TI - Quadratic relationship between early-post-mortem glycolytic rate and beef tenderness. AB - Post-mortem (PM) glycolytic rate in beef M. longissimus thoracis et lumborum (LTL) was controlled by applying low-voltage electrical stimulation (ES) for 1 min at different stages along the slaughter line. The ES treatments were as follows: (1) No electrical stimulation (NES); (2) 75 V to one side of the carcass immediately after splitting; (3) 20-40 V during exsanguination; (4) 75 V either during or following exsanguination. The study utilized 40 bulls and 40 steers. Loin steaks were aged in vacuum pouches 2, 4, 8 and 16 days PM. Quadratic equations utilizing pH at 3 h (pH(3)) gave the best estimate of Warner-Bratzler (WB) shear force for 2, 4, 8 and 16 day steaks. The rate of glycolysis is the primary determinant of LTL tenderness in this study. Temperature may only be important through its influence on early PM glycolytic rate. Optimum tenderness was produced by stimulating carcasses or sides to produce a pH(3) of 6.0. ES application to the carcass either just before or after splitting (treatment 2) produced more desirable and consistent pH(3) responses than either NES or ES during exsanguination. Aging has a differential effect whereby the WB shear values from tougher (leaner bulls) 2 day steaks improve to a greater degree, so they are not different from more tender (fatter steers) steaks by 16 day PM. PMID- 22060265 TI - 'Scharrel' (free range) pigs: Carcass composition, meat quality and taste-panel studies. AB - Carcass conformation, meat quality, fatty acid patterns of backfat and sensory quality characteristics (tenderness, juiciness, smell and taste) of scharrel (free range) pigs and animals from intensive fattening systems were compared. Both groups of pigs consisted of 80 animals, which were slaughtered in batches of 20 pigs per group. The measurements included hot carcass weight, HGP, pH and FOP measurements and a score for intrathoracal fat deposition, all performed early post mortem, and marbling, colour, drip and cooking loss and Warner-Bratzler shear force measurements in loin chops after 1 and 3 days of storage at 4 degrees C. Furthermore, 25% of the carcasses were used in taste-panel analyses. The feed rations used for these 25% of the pigs and their backfat samples were analysed for fatty acid patterns. The overall meat quality of scharrel pigs was not significantly different from that of pigs from intensive fattening systems. W-B shear force values of scharrel pigs were slightly higher. However, this did not coincide with differences in panel tenderness scores. The analytical panel assessed minor differences in taste and smell. The inconsistency of the descriptions concerning these differences did not allow any conclusions. An increase in the amount of linolenic acid was observed in the scharrel pigs' backfat. PMID- 22060266 TI - Determination of papain in raw meat by immunoassay. AB - An antibody raised to papain, a meat tenderising proteolytic enzyme obtained from papaya (Carica papaya), has been used in the development of an enzyme-linked immunoabsorbent assay (ELISA) for the determination of papain in raw meat. Quantitative determinations of papain up to 4 mg/kg of raw meat have been obtained using standard extracts prepared by the exogeneous addition of papain to raw beef. A sample of commercially treated 'tenderised beef' was shown to contain papain at the level of 0.40 mg/kg. In collaboration with a Public Analyst, a papain immunoassay kit has been used to assay 50 samples of beef bought from retail outlets, with a view to monitoring the use of this tenderiser by the meat industry. PMID- 22060267 TI - Objective measurements of pork quality: Evaluation of various techniques. AB - Research has been undertaken in which various methods for meat quality evaluation were compared. The measures used were pH (by homogenization and by combined electrode), light scattering conductivity, dielectric loss factor and colour. A very low incidence of PSE (Pale, Soft, Exudative) and DFD (Dark, Firm, Dry) cases was observed and the correlation between pH, as measured by homogenization and by combined electrode, did not appear to be completely satisfactory. Dielectric loss factor, as measured by the MS tester, seems to be specifically suited for PSE diagnosis. On the other hand, higher values of light scattering and conductivity measured at 24 h post mortem, are found to be linked to the rate of pH fall, even outside the range for PSE. Colour measurements, especially of the parameters L(*), a(*) and hue angle, have given interesting information. In fact, meat could be classified by colour intensity (a(*), psychometric chroma), by type of colour (hue angle) and by exudative phenomena (L(*)). No marked effects of rearing techniques have been observed, whereas the genetic background appears to influence some colour parameters. Slaughter conditions, on the other hand, could affect markedly all the meat quality parameters measured in this research. PMID- 22060268 TI - Objective evaluation of pork quality: Results of on-line measurements. AB - Research has been conducted on objective pork quality evaluation on line in an industrial slaughterhouse. The investigation, which involved more than 5000 pigs, lasted for 12 working days spread over four consecutive weeks between October and November. Measurements performed were Fat-o-Meat'er carcass classification (lean content, fat and muscle thicknesses), cold carcass weight, 24-h pH of Semimembranosus and Biceps femoris muscles and 24-h colour of Semimembranosus muscle. The results show that cold carcass weight and lean content are only slightly related to meat quality as evaluated by pH and colour. Cluster analysis has confirmed the importance of pH and colour parameters, such as L(*), a(*) and hue angle, for the evalaution of pork quality on line in an industrial context. PMID- 22060269 TI - Catalysis of lipid oxidation in muscle model systems by haem and inorganic iron. AB - The catalytic effect of haem proteins (haemoglobin and myoglobin) and inorganic iron (FeSO(4)) on lipid oxidation in a muscle model system was investigated. Haem proteins had a greater prooxidant effect than inorganic iron in raw and heated pork muscle residue when these prooxidants were present at levels approaching those in red meats. The rate of lipid oxidation catalysed by each prooxidant increased as the iron concentration increased over a range of 1-17 MUg/g muscle residue. The relative prooxidant effects of haem protein and inorganic iron were not affected by the mode of addition of the prooxidants to the muscle residue (addition in a concentrated form or dispersed in water), or by the method of cooking (fast versus slow cooking). PMID- 22060270 TI - Skeletal muscle cellularity and histochemistry in response to porcine somatotropin in finishing pigs. AB - The effects of long-term application of recombinant porcine somatotropin (pST) on the development of muscle structure characteristics were examined in finishing pigs from about 120 to 200 days of age. Shot biopsy samples from the longissimus dorsi (longissimus) muscle of 60 Landrace barrows were taken at the initiation of treatment and again after 5 to 10 weeks treatment. The injection of 2 mg pST/d and 4 mg pST/d caused an intense hypertrophy of muscle fibres and resulted in 11% thicker muscle fibres at the end of treatment. In the course of fibre growth, dose-dependent differences occurred. The total muscle fibre number, calculated by muscle cross sectional area and fibre number per unit area of carcass samples, was not influenced. There was a tendency for more nuclei per fibre, whereas the nucleus-cytoplasm ratio seemed to be unchanged, Generally the composition of muscle fibre types (white, intermediate, red or alphaW, alphaR, betaR) was not affected. In pST treatment groups, no more animals with giant fibres were found, nor were higher percentages of this structural anomaly in carcass muscle sections discovered. PMID- 22060271 TI - Influence of pig crossbreed on the composition, volatile compound content and flavour of dry cured ham. AB - The extraction of volatile compounds from dry-cured ham using a dynamic head space method coupled with gas chromatography mass-spectrometry (GC-MS) enabled the identification of a large number of components. Some of these compounds exhibited intense sensory characteristics during odour assessment. Using similar technology, the effect of pig crossbreeds: Landrace * Large-White, Duroc * Gascon Meishan, Pietrain * Gascon-Meishan and Large-White * Gascon-Meishan, on both volatiles and the flavour of dry-cured hams was limited, although differences were observed in aromatic compounds like 1-octen-3-ol (mushroom), 2,3-butanedione and acetoin (butter like). PMID- 22060272 TI - Influence of control parameters in VOCs evolution during MSW trimming residues composting. AB - The influence of control parameters (aeration, moisture, and C/N ratio) during composting of a municipal solid waste (MSW)-legume-trimming residue (LTR) mixture was studied at a pilot plant scale. Factors measured included the composition of the main volatile organic carbons (VOCs) emitted including limonene, beta-pinene, 2-butanone, undecane, phenol, toluene, and dimethyl disulfide. Polynomial models were found to reproduce the experimental results with errors at less than 10%. The relative influence of the independent variables on temperature and selected VOCs followed the order: aeration > moisture > C/N. A high aeration rate results in higher (strong negative effect) values on selected VOCs emissions (41-71% on emitted VOCs variation). Moisture had a positive and negative effect depending on the selected VOCs. A high C/N ratio caused lower production of VOCs except for undecane and 2-butanone. Providing an aerobic environment (0.05 Lair kg(-1) min( 1)), high C/N ratios (>50), and medium moisture (55%) minimize emitted VOCs during MSW composting, ultimately resulting in less odors in the surrounding environment. PMID- 22060273 TI - Evaluation of process- and input-output-based life cycle inventory data with regard to truncation and aggregation issues. AB - Life cycle assessments (LCA) and environmentally extended input-output (EEIO) analyses both strive to account for direct and indirect environmental impacts of goods and services. Different methods have been developed to hybridize these two techniques and minimize the impact of their respective shortcomings on final assessments. These weaknesses, however, have not been extensively studied in a quantitative manner, especially not for complete LCA and EEIO databases. To this end, we jointly analyzed process-based and input-output-based data sets. We first evaluated their complementarity. Though the LCA data was more detailed overall, some sectors of the economy were more precisely represented in the EEIO database. We then contrasted the representation of the different economic sectors in the LCA database with the economic, environmental, and structural importance of these sectors. The weakness of the correlation results led us to conclude that process inventory efforts have not been systematically directed at the most important sectors of the economy. The LCA data was also used to evaluate the sensitivity of EEIO data to aggregation uncertainty. This sensitivity proved highly inhomogeneous. We conclude the presence of important research inefficiencies stemming from the lack of hybrid perspective in the compilation of LCA and EEIO data. PMID- 22060274 TI - ARTEMIN synergizes with TWIST1 to promote metastasis and poor survival outcome in patients with ER negative mammary carcinoma. AB - INTRODUCTION: ARTEMIN (ARTN) is an estrogen regulated growth factor, the expression of which promotes resistance to antiestrogen therapies and predicts poorer survival outcome of patients with estrogen receptor (ER) positive mammary carcinoma (ER+MC) treated with tamoxifen. ARTN is also expressed in ER negative mammary carcinoma (ER-MC). Herein, we determined the role of ARTN in ER-MC and defined the mechanism of action producing poor patient prognosis. METHODS: We modulated the expression of ARTN in two ER- (mesenchymal/claudin-low) mammary carcinoma cell lines (BT549 and MDA-MB-231) by forced expression or small interfering RNA (siRNA) mediated depletion. The effects of modulation of ARTN expression were examined by various in vitro measures of oncogenicity, including the expression of TWIST1 messenger RNA (mRNA) and protein. In vitro results were correlated to xenograft studies in immunodeficient mice. Co-expression of ARTN and TWIST1 and their association to poor survival outcome were examined in a cohort of patients with ER-MC. Pathway analysis was performed by pharmacological inhibition of phosphorylation of AKT (pAKT-Ser 473) or modulation of TWIST1 expression. RESULTS: ARTN expression resulted in ER-MC cells with enhanced mesenchymal characteristics, including increased invasion and a gene expression profile consistent with enhanced mesenchymal phenotype. ARTN stimulated ER-MC cell anchorage independent and 3D matrigel growth, endothelial cell adhesion and transmigration of ER-MC cells through an endothelial cell barrier. Forced expression of ARTN produced a larger, locally invasive tumour mass with tumour emboli that produced distant metastasis. ARTN regulated TWIST1 expression in ER MC cells and ARTN expression was significantly correlated to TWIST1 expression in a panel of mammary carcinoma cell lines and in a cohort of patients with ER-MC. Low expression of both ARTN and TWIST1 predicted 100% relapse free and overall survival in patients with ER-MC, whereas high expression of both ARTN and TWIST1 was associated with a poor survival outcome. ARTN stimulated an increase in TWIST1 expression via increased AKT activity. siRNA mediated depletion of TWIST1 abrogated ARTN stimulated cellular behaviour associated with metastasis, and forced expression of TWIST1 abrogated the functional effects of ARTN depletion. CONCLUSIONS: ARTN and TWIST1 synergize to produce a worse outcome in ER-MC and combined inhibition of ARTN and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) may therefore provide a novel therapeutic strategy in this subtype of mammary carcinoma. PMID- 22060275 TI - Logic feels so good-I like it! Evidence for intuitive detection of logicality in syllogistic reasoning. AB - When people evaluate syllogisms, their judgments of validity are often biased by the believability of the conclusions of the problems. Thus, it has been suggested that syllogistic reasoning performance is based on an interplay between a conscious and effortful evaluation of logicality and an intuitive appreciation of the believability of the conclusions (e.g., Evans, Newstead, Allen, & Pollard, 1994). However, logic effects in syllogistic reasoning emerge even when participants are unlikely to carry out a full logical analysis of the problems (e.g., Shynkaruk & Thompson, 2006). There is also evidence that people can implicitly detect the conflict between their beliefs and the validity of the problems, even if they are unable to consciously produce a logical response (e.g., De Neys, Moyens, & Vansteenwegen, 2010). In 4 experiments we demonstrate that people intuitively detect the logicality of syllogisms, and this effect emerges independently of participants' conscious mindset and their cognitive capacity. This logic effect is also unrelated to the superficial structure of the problems. Additionally, we provide evidence that the logicality of the syllogisms is detected through slight changes in participants' affective states. In fact, subliminal affective priming had an effect on participants' subjective evaluations of the problems. Finally, when participants misattributed their emotional reactions to background music, this significantly reduced the logic effect. PMID- 22060276 TI - Why is test-restudy practice beneficial for memory? An evaluation of the mediator shift hypothesis. AB - Although the memorial benefits of testing are well established empirically, the mechanisms underlying this benefit are not well understood. The authors evaluated the mediator shift hypothesis, which states that test-restudy practice is beneficial for memory because retrieval failures during practice allow individuals to evaluate the effectiveness of mediators and to shift from less effective to more effective mediators. Across a series of experiments, participants used a keyword encoding strategy to learn word pairs with test restudy practice or restudy only. Robust testing effects were obtained in all experiments, and results supported predictions of the mediator shift hypothesis. First, a greater proportion of keyword shifts occurred during test-restudy practice versus restudy practice. Second, a greater proportion of keyword shifts occurred after retrieval failure trials versus retrieval success trials during test-restudy practice. Third, a greater proportion of keywords were recalled on a final keyword recall test after test-restudy versus restudy practice. PMID- 22060277 TI - Feature-based versus category-based induction with uncertain categories. AB - Previous research has suggested that when feature inferences have to be made about an instance whose category membership is uncertain, feature-based inductive reasoning is used to the exclusion of category-based induction. These results contrast with the observation that people can and do use category-based induction when category membership is known. The present experiments examined the conditions that drive feature-based and category-based strategies in induction under category uncertainty. Specifically, 2 experiments investigated whether reliance on feature-based inductive strategies is a product of the lack of coherence in the categories used in previous research or is due to the use of a decision-only induction procedure. Experiment 1 found that feature-based reasoning remained the preferred strategy even when categories with relatively high internal coherence were used. Experiment 2 found a shift toward category based reasoning when participants were trained to classify category members prior to feature induction. Together, these results suggest that an appropriate conceptual representation must be formed through experience with a category before it is likely to be used as a basis for feature induction. PMID- 22060278 TI - Lack of association between polymorphisms in the prostaglandin F2alpha receptor and solute carrier organic anion transporter family 2A1 genes and intraocular pressure response to prostaglandin analogs. AB - PURPOSE: To evaluate the association between variants in the prostaglandin F(alpha) receptor (PTGFR) and solute carrier organic anion transporter family 2A1 (SLCO2A1) genes and intraocular pressure (IOP) response to prostaglandin analogs. METHODS: The medical records of subjects with previously diagnosed open angle glaucoma or ocular hypertension were searched for intraocular pressure measurements before and after prescriptions of prostaglandin analogs. Stored DNA samples were genotyped for the following SNPs: rs3753380 (promoter region) and rs3766355 (intronic region) of the prostaglandin F(2alpha) receptor gene, and rs34550074 (Ala396Thr) of SLCO2A1. The mean change in IOP by genotype was measured. RESULTS: Prostaglandin analogs were prescribed to 267 subjects; 242 (204 right eyes, 205 left eyes) met the inclusion/exclusion criteria for the current study. There was no significant association between genotype and IOP response to prostaglandin analogs (p = 0.48, p = 0.54, p = 0.90). CONCLUSION: In summary, we found no indication for an association between SNPs in the prostaglandin F(2alpha) receptor gene or SLCO2A1 and IOP response to prostaglandin analogs in a population of European descent. PMID- 22060279 TI - Silicone breast implant with intracapsular rupture coexisting with locally advanced carcinoma. PMID- 22060280 TI - Alginate graft copolymers and alginate-co-excipient physical mixture in oral drug delivery. AB - OBJECTIVES: Use of alginate graft copolymers in oral drug delivery reduces dosage form manufacture complexity with reference to mixing or coating processes. It is deemed to give constant or approximately steady weight ratio of alginate to covalently attached co-excipient in copolymers, thereby leading to controllable matrix processing and drug release. This review describes various grafting approaches and their outcome on oral drug release behaviour of alginate graft copolymeric matrices. It examines drug release modulation mechanism of alginate graft copolymers against that of co-excipients in non-grafted formulations. KEY FINDINGS: Drug release from alginate matrices can be modulated through using either co-excipients or graft copolymers via changing their swelling, erosion, hydrophobicity/hydrophilicity, porosity and/or drug adsorption capacity. However, it is not known if the drug delivery performance of formulations prepared using alginate graft copolymers is superior to those incorporating graft-equivalent co excipient physically in a dosage form without grafting but at the corresponding graft weight, owing to limited studies being available. CONCLUSIONS: The value of alginate graft copolymers as the potential alternative to alginate-co-excipient physical mixture in oral drug delivery cannot be entirely defined by past and present research. Such an issue is complicated by the lack of green chemistry graft copolymer synthesis approach, high grafting process cost, complications and hazards, and the formed graft copolymers having unknown toxicity. Future research will need to address these matters to achieve a widespread commercialization and industrial application of alginate graft copolymers in oral drug delivery. PMID- 22060281 TI - Methods for co-culturing tumour and endothelial cells: systems and their applications. AB - OBJECTIVES: The high levels of morbidity and mortality associated with cancer can be attributed to two main processes; the tumour's ability to rapidly proliferate and the process of metastasis. These key processes are facilitated by tumour induced angiogenesis, which causes existing blood vessels to branch off and actively grow towards the tumour providing it with the nutrients and oxygen required for growth and the avenue through which it can metastasise to invade other tissues. This process involves complex interactions between tumour and endothelial cells and is at the forefront of modern biomedical research as anti angiogenic therapies may hold the key to preventing tumour growth and spread. This review looks at modern co-culture systems used in the study of the tumour endothelial cell relationship highlighting the applications and weaknesses of each model and analysing their uses in various tumour-endothelial cell investigations. KEY FINDINGS: The tumour-endothelial cell relationship can be studied in vitro using co-culture systems that involve growing endothelial and tumour cells together so that the effects of dynamic interaction (either by direct cell contact or molecular cross-talk) can be monitored. These co-culture assays are quite accurate indicators of in-vivo growth and therefore allow more effective trialling of therapeutic treatments. CONCLUSIONS: The application of co culture systems are of fundamental importance to understanding the tumour endothelial cell relationship as they offer a method of in-vitro testing that is highly indicative of in-vivo processes. Co-cultures allow accurate testing, which is cost effective and therefore can be utilised in almost all laboratories, is reproducible and technically simple to perform and most importantly has biological relevancy. The importance of this form of testing is such that it warrants further investment of both time and money to enhance the methodology such as to eliminate some of the levels of variability. PMID- 22060282 TI - Hemin-coupled iron(III)-hydroxide nanoparticles show increased uptake in Caco-2 cells. AB - OBJECTIVES: The absorption of commonly used ferrous iron salts from intestinal segments at neutral to slightly alkaline pH is low, mainly because soluble ferrous iron is easily oxidized to poorly soluble ferric iron and ferrous iron but not ferric iron is carried by the divalent metal transporter DMT-1. Moreover, ferrous iron frequently causes gastrointestinal side effects. In iron(III) hydroxide nanoparticles hundreds of ferric iron atoms are safely packed in nanoscaled cores surrounded by a solubilising carbohydrate shell, yet bioavailability from such particles is insufficient when compared with ferrous salts. To increase their intestinal uptake iron(III)-hydroxide nanoparticles were coupled in this study with the protoporphyrin hemin, which undergoes carrier mediated uptake in the intestine. METHODS: Uptake of iron(III)-hydroxide nanoparticles with hemin covalently coupled by DCC reaction was measured in Caco 2 cells with a colorimetric assay and visualized by transmission electron microscopy. KEY FINDINGS: Nanoparticles were taken up by carrier-mediated transport, since uptake was temperature-dependent and increased with an increasing hemin substitution grade. Furthermore, uptake decreased with an increasing concentration of free hemin, due to competition for carrier-mediated uptake. CONCLUSIONS: Hemin-coupled iron(III)-hydroxide nanoparticles were carried by a heme specific transport system, probably via receptor mediated endocytosis. It can be expected that this system shows improved absorption of iron compared with uncoupled iron(III)-hydroxide nanoparticles, which exist on the market today. PMID- 22060283 TI - Spray-dried oil-in-water emulsion to improve the intestinal absorption and oral bioavailability of ZLR-8, a nitric oxide-releasing derivative of diclofenac. AB - OBJECTIVES: Spray-dried emulsion (SDE) was prepared and characterized to improve the intestinal absorption and oral bioavailability of ZLR-8, a nitric oxide releasing derivative of diclofenac, currently under preclinical development. METHODS: The intestinal absorption of ZLR-8 was characterized by single pass intestinal perfusion technique to obtain its absorption and permeability parameters. SDE of ZLR-8 was prepared and characterized by particle size measurements and in-vitro release study. Accurate and precise RP-HPLC methods for the detection of ZLR-8 and its metabolite diclofenac were constructed to perform the bioavailability study. KEY FINDINGS: It was demonstrated that ZLR-8 was absorbed in the whole intestine, of which the duodenum segment exhibited the largest absorption ability. ZLR-8 can be classified into BCS Class 2. SDE significantly enhanced the intestinal absorption rate of ZLR-8 in duodenum and jejunum but had indistinctive effect on permeability. All concentrations of ZLR-8 in rat plasma was lower than the limit of detection. A bicompartment model gave the best fit to the plasma diclofenac concentration-time curves. Calculated on AUC(0-12h) , the mean relative bioavailability of SDE was 105.4-fold that of ZLR 8 suspension. CONCLUSIONS: SDE significantly improved the intestinal absorption of ZLR-8 and resulted in a dramatic improvement in its bioavailability. PMID- 22060284 TI - Formulation of solid dispersion of rebamipide evaluated in a rat model for improved bioavailability and efficacy. AB - OBJECTIVES: Rebamipide, a novel anti-ulcer agent, is listed in biopharmaceutics classification class IV because of its low aqueous solubility and permeability. Consequently, the bioavailability of rebamipide is under 10% in humans. The aim of this study was to increase the solubility and determine the effect of solubility enhancement on the bioavailability and efficacy of rebamipide (RBM). METHODS: After taking into account the physiochemical properties of RBM (solubility, melting point, dosage etc.), solid dispersion was chosen as the solubility enhancement method. A rebamipide solid dispersion system containing the drug, l-lysine, PVP-VA 64 and poloxamer 407 was obtained from a spray-drying method. Solubility enhancement of RBM from the solid dispersion was determined by a dissolution test in 900 ml at pH 1.2. The bioavailability and efficacy of RBM solid dispersion were evaluated in a rat model. KEY FINDINGS: The aqueous solubility of RBM was improved 62.17 times by solid dispersion. The oral bioavailability of the drug was also increased 1.74-fold from solid dispersion compared with the reference product in a rat model. With regard to the anti-ulcer effect, the percentage inhibition of the solid dispersion was 2.71 times higher than that of the reference product in the ulcer-induced rat model. CONCLUSIONS: A solid dispersion of rebamipide was successfully formulated using the spray-drying method. Bioavailability and efficacy of rebamipide were increased significantly by solubility enhancement of the drug. PMID- 22060285 TI - An investigation on the correlation between drug dissolution properties and the growth behaviour of granules in high shear mixer. AB - OBJECTIVES: The aim of this study was to investigate the correlation between the growth behaviour and in-vitro dissolution rate of water-insoluble drugs prepared with high-shear wet granulation. METHODS: Granules containing nimodipine, microcrystalline cellulose, low-substituted hydroxypropylcellulose and aqueous solution of hydroxypropylcellulose were prepared and the effects of independent process variables, including impeller speed and liquid-to-solid ratio were taken into consideration. The mean granule size, granule-size distribution (GSD), porosity and surface properties were monitored at different kneading times to identify the granule-growth mechanisms simultaneously. A computer-based method was applied to simulate the dissolution behaviour of polydisperse granules based on the GSD data. KEY FINDINGS: The in-vitro dissolution rate of drug was high for the early stages of granulation and sharply decreased when coalescence and consolidation of granules started, approaching a flat and low level when granules were sufficiently consolidated. The simulated dissolution results were in agreement with experimental observations and were significantly affected by the GSD, porosity and surface properties of granules during the granulation process. Moreover the GSD was directly related to the granule-growth behaviour and mechanisms. CONCLUSIONS: In general, it was concluded that the dissolution properties of nimodipine basically correlated with the growth behaviour of granules in a high-shear mixer. The simulation method based on GSD can be used as a convenient and rapid way to predict the dissolution properties for formulation development and granulation optimization. PMID- 22060286 TI - A sensitive liquid chromatography coupled with mass spectrometry method for the intracellular and plasma quantification of raltegravir after solid-phase extraction. AB - INTRODUCTION: Liquid chromatography coupled with mass spectrometry for the quantification of raltegravir in human plasma and peripheral blood mononuclear cells has been developed. METHODS: Sample preparations were based on a fully automated solid-phase extraction process. Mass spectrometric data were acquired in a single-ion monitoring method. Raltegravir and quinoxaline, the internal standard, were well separated in a gradient mode over 15 min. KEY FINDINGS: Validation study exhibited excellent linearity, with good intra- and inter-day precision and accuracy. CONCLUSIONS: The assay was successfully applied to the raltegravir quantification in HIV-infected patients. PMID- 22060287 TI - Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats. AB - OBJECTIVES: This study aimed to investigate the antioxidant and anti-inflammatory effects of caffeic acid phenethyl ester (CAPE) on the methotrexate (MTX)-induced hepatorenal oxidative damage in rats. METHODS: Following a single dose of methotrexate (20 mg/kg), either vehicle (MTX group) or CAPE (10 umol/kg, MTX + CAPE group) was administered for five days. In other rats, vehicle (control group) or CAPE was injected for five days, following a single dose of saline injection. After decapitation of the rats, trunk blood was obtained, and the liver and kidney tissues were removed for histological examination and for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels and myeloperoxidase (MPO) and sodium potassium-adenosine triphosphatase (Na(+)/K(+) ATPase) activity. TNF-alpha and IL-1beta levels were measured in the blood. KEY FINDINGS: Methotrexate administration increased the tissue MDA levels, MPO activity and decreased GSH levels and Na(+)/K(+) -ATPase activity, while these alterations were reversed in the CAPE-treated MTX group. Elevated TNF-alpha and IL-1beta levels were also reduced with CAPE treatment. CONCLUSIONS: The results of this study revealed that CAPE, through its anti-inflammatory and antioxidant actions, alleviates methotrexate-induced oxidative damage, which suggests that CAPE may be of therapeutic benefit when used with methotrexate. PMID- 22060288 TI - Analysing the role of COX-2 in acute oesophagitis and in melatonin-exerted protection against experimental reflux oesophagitis in rats. AB - OBJECTIVES: Cyclooxygenase(COX)-2 is implicated in variety of pathophysiological processes, although its role in acute reflux oesophagitis is debatable. This study was designed to evaluate the role of COX-2 during oesophagitis and in melatonin-elicited protection in rats. METHODS: Reflux oesophagitis was induced in rats by ligating the pyloric end and the limiting ridge of the stomach for 5 h. Celecoxib (COX-2 blocker; 10 mg/kg), 16,16-dimethyl prostaglandinE(2) (dmPGE(2); a synthetic analogue of PGE(2) ; 10 ug/kg), melatonin (20 and 40 mg/kg) and omeprazole (10 mg/kg) were given intra-peritoneally 45 min before induction of oesophagitis in rats. Alterations in COX-1 and 2 gene expression and protein levels level were analysed via RT-PCR and Western blotting, respectively. Mucosal PGE(2) level and myeloperoxidase (MPO) activity were measured using an enzyme immunoassay (EIA) kit and spectrophotometrically, respectively. KEY FINDINGS: COX-2 over-expression during reflux oesophagitis promotes inflammation of the oesophagus as celecoxib pretreatment significantly reduced tissue damage and MPO activity in rats with reflux oesophagitis (RE-rats). By contrast, dmPGE(2) pretreatment significantly exacerbated tissue injury and simultaneously increased COX-2 expression, PGE(2) levels and MPO activity in RE-rats. Further, melatonin pretreatment significantly reduced the tissue injury, COX-2 over expression, PGE(2) level and MPO activity in RE-rats. Melatonin offered more potent suppression of COX-2, PGE(2) and MPO activity than the proton-pump inhibitor omeprazole; however, both reduced the lesion injury to a similar extent. Melatonin at a dose of 20 mg/kg failed to inhibit significantly the dmPGE(2) -induced tissue damage, COX-2 expression, PGE(2) level and MPO activity in RE-rats while at a higher dose of 40 mg/kg it significantly attenuated these changes. CONCLUSION: Our results suggest that COX-2 plays an important pro inflammatory role during acute reflux oesophagitis in rats and its inhibition contributes significantly to melatonin-exerted protection against reflux oesophagitis. PMID- 22060289 TI - Ergosta-4,6,8(14),22-tetraen-3-one isolated from Polyporus umbellatus prevents early renal injury in aristolochic acid-induced nephropathy rats. AB - OBJECTIVES: Aristolochic acid (AA) nephropathy, first reported as Chinese herbs nephropathy, is a rapidly progressive tubulointerstitial nephropathy that results in severe anemia, interstitial fibrosis and end-stage renal disease. Tubulointerstitial injury was studied in a rat model of AA nephropathy to determine whether ergosta-4,6,8(14),22-tetraen-3-one (ergone) treatment prevents early renal injury in rats with aristolochic acid I-induced nephropathy. METHODS: Early renal injury via renal interstitial fibrosis was induced in rats by administration of aristolochic acid I (AAI) solution intragastrically for 8 weeks. Ninety-six rats were randomly divided into four groups (n = 24/group): (1) control (2) AAI (3) AAI + ergone (10 mg/kg) and (4) AAI + ergone (20 mg/kg). Blood and urine samples were collected and rat were sacrificed for histological assessment of the kidneys on at the end of weeks 2, 4, 6 and 8. KEY FINDINGS: AAI caused progressive elevation of blood urea nitrogen, creatinine, potassium, sodium, chlorine, proteinuria and urinary N-acetyl-beta-D-glucosaminidase (NAG). Ergone suppressed elevation of blood urea, nitrogen, creatinine, proteinuria and urinary NAG to some degree, but the AAI-ergone-treated group did not differ from AAI-treated group for body weight, serum potassium, sodium and chlorine. The progress of the lesions in the kidney after AAI administration was also observed by histopathological examinations, but kidneys from rats of AAI-ergone-treated group displayed fewer lesions. CONCLUSIONS: Ergone treatment conferred protection against early renal injury in a rat model of AA nephropathy. Early administration of ergone may prevent the progression of renal injury and the subsequent renal fibrosis in AA nephropathy. PMID- 22060290 TI - Monascus purpureus-fermented rice inhibits tumor necrosis factor-alpha-induced upregulation of matrix metalloproteinase 2 and 9 in human aortic smooth muscle cells. AB - OBJECTIVES: Inflammation is associated with atherosclerosis. Cholestin (Monascus purpureus-fermented rice) contains a naturally occurring statin, which has lipid modulating, anti-inflammatory and antioxidative effects. This study aimed to investigate the effects of Cholestin extract on the expression of matrix metalloproteinase (MMP)-2 and MMP-9 by tumor necrosis factor (TNF)-alpha-treated human aortic smooth muscle cells (HASMCs). METHODS: Zymography, reverse transcription polymerase chain reaction and immunoblot analyses were used for analysis of MMP expression of TNF-alpha-stimulated HASMCs. Gel shift assay was used for analysis of transcription factor nuclear factor-kappaB (NF-kappaB) activation. Intracellular reactive oxygen species (ROS) generation was also analysed. KEY FINDINGS: The supplement of HASMCs with Cholestin extract significantly suppresses enzymatic activities of MMP-2 and MMP-9 in TNF-alpha stimulated HASMCs. RT-PCR and immunoblot analyses show that Cholestin extract significantly attenuates TNF-alpha-induced mRNA and protein expressions of MMP-2 and MMP-9. Gel shift assays show that Cholestin treatment reduces TNF-alpha activated NF-kappaB. Furthermore, Cholestin also attenuates intracellular ROS generation in TNF-alpha-treated HASMCs. The supplement with an ROS scavenger N acetyl-cysteine (glutathione precursor) gives similar results to Cholestin. CONCLUSIONS: Cholestin reduces TNF-alpha-stimulated MMP-2 and MMP-9 expression as well as downregulating NF-kappaB activation and intracellular ROS formation in HASMCs, supporting the notion that the natural compound Cholestin may have potential application in clinical atherosclerosis disease. PMID- 22060291 TI - Effects of Ganoderma lucidum polysaccharides on IEC-6 cell proliferation, migration and morphology of differentiation benefiting intestinal epithelium healing in vitro. AB - OBJECTIVES: Restoration of epithelial continuity in the intestinal surface after extensive destruction is important since intestinal epithelial cells stand as a boundary between the body's internal and external environment. Polysaccharides from Ganoderma lucidum (Gl-PS) may benefit intestinal epithelial wound healing in different aspects, which awaits clarification. To identify potential effects, a non-transformed small-intestinal epithelial cell line, IEC-6 cells, was used. METHODS: Effects on epithelial cell proliferation, migration, morphology of differentiation and transforming growth factor beta (TGF-beta) protein expression, as well as the cellular ornithine decarboxylase (ODC) mRNA and c-Myc mRNA expression, were assessed, respectively, by MTT assay, wound model in vitro, observation under a microscope after hematoxylin and eosin staining, enzyme linked immunosorbent assay and reverse transcription-polymerase chain reaction assays. KEY FINDINGS: It was shown that Gl-PS stimulated IEC-6 cell proliferation and migration significantly in a dose-dependent manner; 10 ug/ml Gl-PS improved the morphology of differentiation in IEC-6 cells. Inefficacy in expression of TGF beta in IEC-6 cells indicated a possible TGF-beta independent action of Gl-PS. However, Gl-PS increased ODC mRNA and c-Myc mRNA expression in a dose-dependent manner, indicating, at least partially possible involvement of ODC and c-Myc gene expression in improvement of intestinal wound healing. CONCLUSIONS: These results suggest the potential usefulness of Gl-PS to cure intestinal disorders characterized by injury and ineffective repair of the intestinal mucosa. PMID- 22060292 TI - Curcumin: a potential therapeutic polyphenol, prevents noradrenaline-induced hypertrophy in rat cardiac myocytes. AB - OBJECTIVES: This study was designed to evaluate the effect of curcumin on H9c2 cardiac cell line and primary rat cardiac myocytes, using purified noradrenaline as a hypertrophy-inducing agent. METHODS: The concentration of curcumin at which cells were treated was determined by MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assay. The effect of this safe dose in preventing noradrenaline-induced cardiac hypertrophy was assessed by biochemical analysis (estimating total protein content), molecular analysis (using RT-PCR to study the expression of fetal genes like ANF), immunological analysis (by determining the nuclear localization of GATA-4) and electrophoretic mobility shift assay (EMSA; to study DNA binding activity of GATA-4). KEY FINDINGS: Curcumin at a concentration of 8 um was found to suppress the increase in cell size, protein content and enhanced marker gene expression (ANF) caused by noradrenaline. Immunocytochemistry and Western blot analysis showed that curcumin suppressed the localization of transcription factor GATA-4 in the nucleus. It also showed a reduced DNA-binding activity in the presence of noradrenaline as confirmed by EMSA. CONCLUSIONS: These findings suggest that curcumin reduces the hypertrophic marker gene expression by inhibiting nuclear localization and DNA binding activity of GATA-4. Thus it has a great anti-hypertrophic potential. PMID- 22060293 TI - Effects of various flavonoids isolated from Scutellaria baicalensis roots on skin damage in acute UVB-irradiated hairless mice. AB - OBJECTIVES: Solar ultraviolet (UV) radiation causes skin damage including increasing skin thickness, edema and flush. Scutellaria baicalensis roots have been traditionally used as a remedy for allergic inflammatory diseases in China and Japan. In this study, we examined the effects of four flavonoids isolated from these roots, namely 2',5, 5',7-tetrahydroxy-6',8-dimethoxyflavone (1), skullcapflavone II (2), 2(S)-2',5,6',7-tetrahydroxyflavanone (3) and 2(R), 3(R) 2',3,5,6',7-pentahydroxyflavanone (4), on acute UVB irradiation-induced skin damage in hairless mice. METHODS: The four flavonoids were orally administered twice daily, at doses of 10 and 50 mg/kg, for 14 consecutive days. The UVB irradiation was performed at a dose of 200 mJ cm(-2) on days 7 and 8 after beginning oral administration of the four flavonoids. KEY FINDINGS: Compounds 1 and 4 prevented increases in skin thickness, levels of matrix metalloproteinases (MMP)-2 and MMP-9, and vascular endothelial growth factor (VEGF) induced by UVB irradiation. The other two flavonoids 2 and 3 had no effect. CONCLUSIONS: Compounds 1 and 4 isolated from Scutellaria baicalensis roots may be useful for preventing skin inflammation induced by acute UVB irradiation. PMID- 22060296 TI - Obituary: dr w. J. Scott (1911-1993). PMID- 22060294 TI - Summer-winter switching of the Ramadan fasts in people with diabetes living in temperate regions. PMID- 22060297 TI - 1,5-glucono-delta-lactone-induced gelation of myofibrillar protein at chilled temperatures. AB - In this study 1,5-glucono-delta-lactone was used to achieve acid-induced gelation of myofibrillar proteins at 4 degrees C. The characteristics of the myofibrillar gels were investigated by measuring Young's modulus and springiness. The effects of addition of sodium chloride and tetrasodium pyrophosphate on gel characteristics were also studied. Sodium chloride increased the Young's modulus of myofibrillar protein gels in the presence and absence of 1,5-glucono-delta lactone, while tetrasodium pyrophosphate had no observable effect on the gels until the pH decreased to 4.1, when the Young's modulus was enhanced. PMID- 22060298 TI - Ultrastructural changes of myofibrillar protein gelled with 1,5-glucono-delta lactone at chilled temperatures. AB - Changes in the ultrastructure of myofibrillar protein as a result of 1,5-glucono delta-lactone-induced gelation at chilled temperatures were investigated using transmission electron microscopy. The myofibril structure appeared to have completely disintegrated at pH 4.0 resulting in a granular, amorphous appearance. It was suggested that as the pH was lowered to about 4.5, partial extraction of the A-band proteins occurred. A composite system of a myosin gel network reinforced by the residual myofibrillar structure was proposed to have formed. As the pH was lowered further, complete depolymerisation of actomyosin was suggested to have resulted in the formation of a predominantly myosin gel. The inclusion of sodium chloride resulted in swelling of the myofibrillar protein and retention of the myofibrillar structure to pH 3.8. PMID- 22060299 TI - Chemical, physical and sensory attributes for the characterization of an Italian dry-cured sausage. AB - This work was designed to characterize Felino salami, an Italian dry-cured sausage. For this purpose, a wide range of chemical, physical and sensory parameters were studied in 29 samples. Seven chemical and physical variables were selected by using principal components analysis: namely, pH, NaCl/moisture, moisture/protein, soluble N/protein, lactic acid, elasticity index and sample luminosity (L(*)). The first two principal components were significant according to double-cross validation and accounted for 79% of variance. The seven-variable chemometric model shows that variability in the first principal component is determined by variables expressing the acidity and the extent of lactic fermentation, while the second component is determined by variables expressing the degree of ripening and is related to the sensory scores maturation and hardness, and to salami age (p < 0.001). Sensory scores were evaluated by a multivariate method to verify the consonance among assessors as to the different attributes. The semi-trained panel was consonant and reliable for five of the nine sensory attributes evaluated. The predictive ability of the chemometric model for the sensory attributes was assessed with cross-validation. PMID- 22060300 TI - Potassium chloride, potassium lactate and glycine as sodium chloride substitutes in fermented sausages and in dry-cured pork loin. AB - Salt is essential in the elaboration of dry meat products, contributing to their texture and flavour development. The effect brought about by substituting NaCl with KCl (0-60%), potassium lactate (0-100%) and glycine (0-100%) on the texture, flavour and colour characteristics of fermented sausages and dry-cured pork loins was evaluated. Texture profile analysis and a sensory analysis were performed. Important flavour defects were detected with substitutions above 40% for the three substituents in both products, and with substitutions above 30% for glycine in dry-cured loin. A loss of cohesiveness was detected by the sensory analysis in fermented sausages at substitution levels higher than 30% with potassium lactate (K-lactate) and higher than 50% with glycine. Although the instrumental analysis detected texture changes in dry-cured loin, the sensory analysis did not detect any substitution effect on texture. PMID- 22060301 TI - Effect of pre-rigor stretch and various constant temperatures on the rate of post mortem pH fall, rigor mortis and some quality traits of excised porcine biceps femoris muscle strips. AB - Porcine biceps femoris strips of 10 cm original length were stretched by 50% and fixed within 1 hr post mortem then subjected to temperatures of 4 degrees , 15 degrees or 36 degrees C until they attained their ultimate pH. Unrestrained control muscle strips, which were left to shorten freely, were similarly treated. Post-mortem metabolism (pH, R-value) and shortening were recorded; thereafter ultimate meat quality traits (pH, lightness, extraction and swelling of myofibrils) were determined. The rate of pH fall at 36 degrees C, as well as ATP breakdown at 36 and 4 degrees C, were significantly reduced by pre-rigor stretch. The relationship between R-value and pH indicated cold shortening at 4 degrees C. Myofibrils isolated from pre-rigor stretched muscle strips kept at 36 degrees C showed the most severe reduction of hydration capacity, while paleness remained below extreme values. However, pre-rigor stretched myofibrils - when stored at 4 degrees C - proved to be superior to shortened ones in their extractability and swelling. PMID- 22060302 TI - The effects of the ultimate pH of meat on tenderness changes during ageing. AB - A range of ultimate pH (pH(u)) values, from 5.4 to 7.2, was produced in the m. longissimus thoracicum et lumborum (LD) of 55 sheep by subcutaneous injections of adrenaline, or by injection and subsequent exercise. The rate constant of ageing for each of 47 animals was calculated from shear force measurements, taken at intervals for up to 5 days from the LD held at 12 dgC. The relationship between the ageing rate and pH(u) could be adequately described by the equation rate constant (k) = 4.109 - 1.349(pH) + 0.1111(pH)(2); r(2) = 0.707, with a minimum rate constant at pH 6.07. The loin muscles from eight carcasses were selected to determine the effects of ultimate pH on the initial, unaged toughness value. Calpain activity was inhibited by intramuscular injection of ZnCl(2) dissolved in saline, and the muscles were aged at 10-12 degrees C on the carcass for up to 6 days. At all values of pH(u) (5.4-6.7), tenderness as measured by shear force were equivalent, from which it was concluded that the initial toughness of unaged lamb was not affected by pH(u). In the contralateral, untreated muscle, ageing was measured using both shear force measurement and changes in the myofibrillar fragmentation index (MFI). After 1 day, the intermediate pH range (5.8-6.2) has the highest shear force and the lowest fragmentation index value. However, in contrast to the shear force values, the ultimate MFI value in aged muscle was lowest in the high pH(u) range (6.4-6.7; minimum value at 6.4). The highest fragmentation values were found at the low pH(u) range. These observations suggest that pH(u)-related tenderness differences in meat result from different rates of ageing in the post rigor period, and therefore that these differences disappear following a sufficient ageing period. The slowest rate of tenderization measured on cooked meat was observed at pH(u) values around 6.07, but the least fragmentation of raw meat was observed at pH(u) values around 6.4, a difference of almost 0.33 pH unit. PMID- 22060303 TI - Influence of protein isolate from lupin seeds (Lupinus albus ssp. Graecus) on processing and quality characteristics of frankfurters. AB - Lupin protein isolate (92% protein) from seeds of Lupinus albus ssp. Graecus (LSPI) was used as powder ingredient for the manufacture of frankfurters at levels 0, 1, 2 and 3% of the formulation weight. Additional 1% water was added during batter formulation to each 1% protein used. LSPI increased (P < 0.05) the pH and viscosity of batter and reduced the jelly separation. Increasing the LSPI level resulted in higher (P < 0.05) processing yield and lower (P < 0.05) purge accumulation, redness and visual colour scores and hardness of frankfurters. Significant differences in overall acceptability were not found among the control and frankfurters with 1% and 2% LSPI. Frankfurters with 3% LSPI were judged as unacceptable. Incorporation of LSPI at 1% level either in hydrated form or as stabilizer in pre-emulsified fat improved the processing characteristics and overall acceptability of frankfurters made with LSPI as powder ingredient and did not affect the color and texture. PMID- 22060304 TI - Rapid method for determining water-holding capacity in meat using video image analysis and simple formulae. AB - To accelerate measurement of the water-holding capacity (WHC) of meat by the press method, video image analysis (VIA) and formulae were investigated. The areas of meat and meat liquid on filter paper were little affected by changes in the operating conditions of the VIA system. VIA is associated with greater repeatability, less variation due to operators and was less time consuming than planimetry. When VIA was applied to a variety of fresh meats (beef, pork, chicken and duck meat), it was possible to measure the areas of meat and liquid on filter paper under a translucent plastic plate, immediately after pressing, without drawing an outline of the meat area. VIA was also able to measure cooked meat. Drying on filter paper decreased the areas of meat and liquid slightly but hardly changed the meat/liquid area ratio. The meat/liquid area ratio was correlated (P < 0.01, r = 0.92) with the WHC measurements obtained by conventional formulae including sample moisture. VIA combined with mmeat/liquid ratio is a rapid stable and efficient technique for measuring WHC by the press method. PMID- 22060305 TI - TBA test by an extractive method applied to 'pate'. AB - The aim of this work was to study the influence of different conditions on the thiobarbituric acid (TBA) test, determined by the extractive method, as a measure of lipid oxidation in 'pate'. Different extracting agents (trichloroacetic acid and trichloroacetic acid in 2 M phosphoric acid), different concentrations of these acids (10, 15 and 20%), different reaction times and temperatures (35 min at 100 degrees C and 900 min at room temperature) and the effect of sulfanilamide additions were evaluated. All the samples were measured by HP 8451A Diode ARRAY spectrophotometer at 532 nm. Significant differences between 35 and 900 min of MA-TBA reaction time were found. Highest TBA numbers were found in samples with a reaction time of 35 min in a thermostatically controlled waterbath at 100 degrees C, rather than 900 min at room temperature. Lowest TBA numbers were found in samples with the addition of sulfanilamide rather than without it. The 10% TCA solution gave the best recovery percentages for 'pate', making it the preferred extractant. PMID- 22060306 TI - Use of electrical stimulation, hot processing and carrageenan for processing low fat ground beef patties. AB - Three studies were conducted to determine the effects of electrical stimulation, hot processing and carrageenan usage on sensory, shear force and cooking properties of low-fat (5, 10%) beef patties. The right or left sides of beef carcasses assigned to electrical stimulation (ES) received 600 V pulsating current for 120 s. Non-stimulated (NS) sides were also included for comparisons. Sides subjected to hot processing (HP) were boned 90 min post-exsanguination. Cold processing (CP) was initiated 48 h post mortem. Formulations for the manufacture of patties included the use of carrageenan [none, 0.5% iota (iota), 0.5% kappa (kappa)]. Patties from NSHP beef had higher pH and cooking yields, less shrink in patty dimensions during cooking and lower shear force values than patties from NSCP controls (P < 0.05). ES improved tenderness and juiciness of CP patties, while ESHP patties exhibited higher cooking yields than NSCP patties. Tenderness was improved in two of the three studies as a result of increasing the fat content from 5 to 10%. Use of iota-carrageenan provided improvements in tenderness and juiciness over patties receiving no carrageenan or kappa carrageenan. Processors should consider HP with 1.0% added salt (improved cooking yields, patty configuration, tenderness) and the use of iota-carrageenan (improved tenderness and juiciness) for low-fat beef patties. PMID- 22060308 TI - Full-thickness local soft tissue atrophy following steroid injection to greater occipital nerve. PMID- 22060309 TI - The coronary sinus reducer stent for the treatment of chronic angina pectoris. PMID- 22060310 TI - The neuropathic pain diagnosed with the grading system is different from pain defined with the definition of neuropathic pain. PMID- 22060312 TI - alpha-Haemoglobin regulates sympathoadrenal cell metabolism to maintain a catecholaminergic phenotype. AB - Discovery of haemoglobin A expression outside of the erythroid cell lineage suggests that oxygen transport is the main, but not the unique, function of adult haemoglobin chains in mammals. The contribution of haemoglobin A to antioxidant defences has been proposed in the territories where it is expressed. Catecholaminergic cells rely on an active oxidative metabolism to accomplish their biological function, but are exposed to strong oxidative stress due to metabolism of catecholaminergic transmitters. We show in the present study that peripheral catecholaminegic cells express the alpha- and not the beta-haemoglobin A chains, and that alpha-haemoglobin expression could modulate the antioxidant capabilities of these cells. We also show that alpha-haemoglobin overexpression in PC12 cells leads to a selective increase of tyrosine hydroxylase synthesis and activity. This is achieved by means of a reorganization of antioxidant defences, decreasing cytoplasmic glutathione peroxidase and superoxide dismutase, and increasing mitochondrial peroxidase. Moreover, alpha-haemoglobin induces a decrease in lipogenesis and increase in lipid degradation, situations that help save NAD(P)H and favour supply of acetyl-CoA to the tricarboxylic acid cycle and production of reducing equivalents in the cell. All of these results point to a role for alpha-haemoglobin as a regulator of catecholaminergic cell metabolism required for phenotype acquisition and maintenance. PMID- 22060313 TI - Effect of chain unsaturation on the self-association of tri- and tetraethylene glycol octyl ethers obtained by butadiene telomerization. AB - 2,7-Octadienyl ethers of tri- and tetraethylene glycol (C(8:2)E(3) and C(8:2)E(4)) have been synthesized by the atom-economical butadiene telomerization of the corresponding poly(ethylene glycols). On one hand, this synthetic path is attractive because it is expeditious and environmentally benign, and on the other hand, it provides unconventional amphiphiles for which the lipophilic chains possess two double bonds. These two unsaturations increase the global hydrophilicity of the compound, which is also highlighted by the modelization of the compounds using the conductor-like screening model for real solvents (COSMO RS). The behavior of C(8:2)E(3) and C(8:2)E(4) in binary amphiphile/water and ternary amphiphile/oil/water systems is therefore greatly modified compared to that of the conventional fully saturated homologues (C(8)E(3) and C(8)E(4)) that are easily obtained after hydrogenation. This results in a lowered efficiency of the unsaturated compounds for oil solubilization. The usual Winsor-type microemulsion systems are formed, and for the same oil, the DLS investigation of the microstructure of the Winsor I microemulsion does not highlight any difference in the self-association between the unsaturated and saturated compounds. PMID- 22060314 TI - Composition and antibacterial activity of essential oil from Scutellaria grossa Wall ex Benth. AB - The chemical composition of the steam volatile oil of the whole aerial part of Scutellaria grossa Wall ex Benth. (Lamiaceae), obtained by steam distillation, has been analysed by capillary GC and GC-MS. The oil was found to be rich in oxygenated monoterpenes (88.6%). A total of 50 constituents were identified, representing 94.4% of the total oil composition. Linalool (37.0%) and 1-octen-3 ol (32.0%) were found to be the principal constituents. The antibacterial activity of the oil was determined against 10 bacterial strains by measuring the growth inhibitory zones. The oil showed significant antibacterial activity against Gram-positive bacteria, Bacillus subtilis and Enterococcus faecalis, and the Gram-negative, Klebsiella pneumoniae and Salmonella enterica enterica. A minimum inhibitory concentration of 31.25 uL mL(-1) was observed against E. faecalis. PMID- 22060315 TI - The association of health and employment in mature women: a longitudinal study. AB - BACKGROUND: Despite a reduction in income inequalities between men and women, there is still a large gap between income and retirement savings of Australian men and women. This is especially true for women who have health or disability problems. Mature age women are closest to retirement and, therefore, have less chance than younger women to build up enough retirement savings and may need to continue working to fund their older age. Continued workforce participation may be particularly difficult for women who are less healthy. Understanding which health problems lead to a decrease in workforce participation among mature age women is crucial. Therefore, this longitudinal study sought to identify which health problems are associated with employment among midage women over time. METHODS: Data were analyzed from the midage cohort of the Australian Longitudinal Study on Women's Health (ALSWH), which involved 14,200 midage women (aged 45-50 years in 1996). The women have been surveyed four additional times, in 1998, 2001, 2004, and 2007. Generalized estimating equations (GEE) were used to conduct nested multivariate longitudinal analyses. RESULTS: The percentages of women who were employed in the years 2001, 2004, and 2007 were 77%, 72%, and 68%, respectively. Results were adjusted for sociodemographic variables. Being employed decreased as physical and mental health deteriorated and with self reported conditions: diabetes, high blood pressure, depression, anxiety, and other psychiatric conditions. Back pain, arthritis, cancer, obesity, and being a current smoker are associated with employment but not when quality of life is added to the model. CONCLUSIONS: There were significant associations between health and employment. Understanding these relationships could inform policies and guidelines for preventing declines in employment in mature age women. PMID- 22060316 TI - Negative velocity fluctuations of pulled reaction fronts. AB - The position of a reaction front, propagating into an unstable state, fluctuates because of the shot noise. What is the probability that the fluctuating front moves considerably slower than its deterministic counterpart? Can the noise arrest the front motion for some time, or even make it move in the wrong direction? We present a WKB theory that assumes many particles in the front region and answers these questions for the microscopic model A?2A and random walk. PMID- 22060317 TI - Unraveling a Brownian particle's memory with effective mode chains. AB - Memory effects in quantum dynamical processes involving structured environments are presently difficult, if not impossible, to investigate using standard approaches. Progress can be made by transforming the environmental variables to a suitable chain representation which effectively performs a Markovian embedding of the dynamics. Here, we show that this effective-mode chain representation provides a unique way of unraveling the memory kernel kappa(t) as a function of time. Truncated or Markov-closed chains with n effective modes exactly reproduce kappa(t) to the 4nth order in time, up to an irrelevant constant of order kappa(0)/n. These favorable convergence properties pave the way for efficient quantum simulations of fast (non-Markovian) processes by reduced dynamical models. PMID- 22060318 TI - Stochastic treatment of finite-N effects in mean-field systems and its application to the lifetimes of coherent structures. AB - A stochastic treatment yielding to the derivation of a general Fokker-Planck equation is presented to model the slow convergence toward equilibrium of mean field systems due to finite-N effects. The thermalization process involves notably the disintegration of coherent structures that may sustain out-of equilibrium quasistationary states. The time evolution of the fraction of particles remaining close to a mean-field potential trough is analytically computed. This indicator enables to estimate the lifetime of coherent structures and thermalization time scale in mean-field systems. PMID- 22060319 TI - Molten salt eutectics from atomistic simulations. AB - Despite their importance for solar thermal power applications, phase-diagrams of molten salt mixture heat transfer fluids (HTFs) are not readily accessible from first principles. We present a molecular dynamics scheme general enough to identify eutectics of any HTF candidate mixture. The eutectic mixture and temperature are located using the liquid mixture free energy and the pure component solid-liquid free energy differences. The liquid mixture free energy is obtained using thermodynamic integration over particle identity transmutations sampled with molecular dynamics at a single temperature. Drawbacks of conventional phase diagram mapping methodologies are avoided by not considering solid mixtures, thereby evading expensive computations of solid phase free energies. Numerical results for binary and ternary mixtures of alkali nitrates agree well with experimental measurements. PMID- 22060320 TI - Isostaticity of constraints in amorphous jammed systems of soft frictionless Platonic solids. AB - The average number of constraints per particle in mechanically stable amorphous systems of Platonic solids approaches the isostatic limit at the jamming point (->12), though average number of contacts are hypostatic. By introducing angular alignment metrics to classify the degree of constraint imposed by each contact, constraints are shown to arise as a direct result of local orientational order reflected in edge-face and face-face alignment angle distributions. With approximately one face-face contact per particle at jamming, chainlike face-face clusters form with finite extent--a signature of amorphous jammed systems. PMID- 22060321 TI - Incompressibility of polydisperse random-close-packed colloidal particles. AB - We use confocal microscopy to study the compressibility of a random-close-packed sample of colloidal particles. To do this, we introduce an algorithm to estimate the size of each particle. Taking into account their sizes, we compute the compressibility of the sample as a function of wave vector q, and find that this compressibility vanishes linearly as q->0, showing that the packing structure is incompressible. The particle sizes must be considered to calculate the compressibility properly. These results also suggest that the experimental packing is hyperuniform. PMID- 22060322 TI - Instability of a uniformly collapsing cloud of classical and quantum self gravitating Brownian particles. AB - We study the growth of perturbations in a uniformly collapsing cloud of self gravitating Brownian particles. This problem shares analogies with the formation of large-scale structures in a universe experiencing a "big-crunch" or with the formation of stars in a molecular cloud experiencing gravitational collapse. Starting from the barotropic Smoluchowski-Poisson system, we derive a new equation describing the evolution of the density contrast in the comoving (collapsing) frame. This equation can serve as a prototype to study the process of self-organization in complex media with structureless initial conditions. We solve this equation analytically in the linear regime and compare the results with those obtained by using the "Jeans swindle" in a static medium. The stability criteria, as well as the laws for the time evolution of the perturbations, differ. The Jeans criterion is expressed in terms of a critical wavelength lambda(J) while our criterion is expressed in terms of a critical polytropic index gamma(4/3). In a static background, the system is stable for lambdalambda(J). In a collapsing cloud, the system is stable for gamma>gamma(4/3) and unstable for gammalambda(J). We also study the fragmentation process in the nonlinear regime. We determine the growth of the skewness, the long-wavelength tail of the power spectrum and find a self-similar solution to the nonlinear equations valid for large times. Finally, we consider dissipative self-gravitating Bose-Einstein condensates with short-range interactions and show that, in a strong friction limit, the dissipative Gross-Pitaevskii-Poisson system is equivalent to the quantum barotropic Smoluchowski-Poisson system. This yields new types of nonlinear mean-field Fokker-Planck equations, including quantum effects. PMID- 22060323 TI - Glassy phases and driven response of the phase-field-crystal model with random pinning. AB - We study the structural correlations and the nonlinear response to a driving force of a two-dimensional phase-field-crystal model with random pinning. The model provides an effective continuous description of lattice systems in the presence of disordered external pinning centers, allowing for both elastic and plastic deformations. We find that the phase-field crystal with disorder assumes an amorphous glassy ground state, with only short-ranged positional and orientational correlations, even in the limit of weak disorder. Under increasing driving force, the pinned amorphous-glass phase evolves into a moving plastic flow phase and then, finally, a moving smectic phase. The transverse response of the moving smectic phase shows a vanishing transverse critical force for increasing system sizes. PMID- 22060324 TI - Principal axes for stochastic dynamics. AB - We introduce a general procedure for directly ascertaining how many independent stochastic sources exist in a complex system modeled through a set of coupled Langevin equations of arbitrary dimension. The procedure is based on the computation of the eigenvalues and the corresponding eigenvectors of local diffusion matrices. We demonstrate our algorithm by applying it to two examples of systems showing Hopf bifurcation. We argue that computing the eigenvectors associated to the eigenvalues of the diffusion matrix at local mesh points in the phase space enables one to define vector fields of stochastic eigendirections. In particular, the eigenvector associated to the lowest eigenvalue defines the path of minimum stochastic forcing in phase space, and a transform to a new coordinate system aligned with the eigenvectors can increase the predictability of the system. PMID- 22060326 TI - Brownian dynamics of a self-propelled particle in shear flow. AB - Brownian dynamics of a self-propelled particle in linear shear flow is studied analytically by solving the Langevin equation and in simulation. The particle has a constant propagation speed along a fluctuating orientation and is additionally subjected to a constant torque. In two spatial dimensions, the mean trajectory and the mean square displacement (MSD) are calculated as functions of time t analytically. In general, the mean trajectories are cycloids that are modified by finite temperature effects. With regard to the MSD, different regimes are identified where the MSD scales with t(nu) with nu=0,1,2,3,4. In particular, an accelerated (nu=4) motion emerges if the particle is self-propelled along the gradient direction of the shear flow. PMID- 22060325 TI - Periodic one-dimensional hopping model with transitions between nonadjacent states. AB - A one-dimensional hopping model is useful for describing the motion of microscopic particles in a thermal noise environment. Recent experiments on the new generation of light-driven rotary molecular motors found that a motor in state i can jump forward to state i+1 or i+2 or backward to state i-1 or i-2 directly. In this paper, inspired by these experiments, such a modified periodic one-dimensional hopping model with arbitrary period N is studied theoretically. The mean velocity, effective diffusion constant, and mean dwell time in one single mechanochemical cycle are obtained. The corresponding results are illustrated and verified by being applied to the synthetic rotary molecular motors. PMID- 22060327 TI - Multispecies model with interconversion, chipping, and injection. AB - Motivated by the phenomenology of transport through the Golgi apparatus of cells, we study a multispecies model with boundary injection of one species of particle, interconversion between the different species of particle, and driven diffusive movement of particles through the system by chipping of a single particle from a site. The model is analyzed in one dimension using equations for particle currents. It is found that, depending on the rates of various processes and the asymmetry in the hopping, the system may exist either in a steady phase, in which the average mass at each site attains a time-independent value, or in a "growing" phase, in which the total mass grows indefinitely in time, even in a finite system. The growing phases have interesting spatial structure. In particular, we find phases in which some spatial regions of the system have a constant average mass, while other regions show unbounded growth. PMID- 22060328 TI - Universal and nonuniversal amplitude ratios for scaling corrections on Ising strips. AB - We consider strips of Ising spins at criticality. For strips of width N sites, subdominant (additive) finite-size corrections to scaling are assumed to be of the form a(k)/N(k) for the free energy, and b(k)/N(k) for inverse correlation length, with integer values of k. We investigate the set {a(k),b(k)} (k>=2) by exact evaluation and numerical transfer-matrix diagonalization techniques, and their changes upon varying anisotropy of couplings, spin quantum number S, and (finite) interaction range, in all cases for both periodic (PBCs) and free (FBCs) boundary conditions across the strip. We find that the coefficient ratios b(k)/a(k) remain constant upon varying coupling anisotropy for S=1/2 and first neighbor couplings, for both PBCs and FBCs (albeit at distinct values in either case). Such apparently universal behavior is not maintained upon changes in S or interaction range. PMID- 22060329 TI - Noise associated with nonconservative forces in optical traps. AB - It is known that for a particle held in an optical trap the interaction of thermal fluctuations with a nonconservative scattering force can cause a persistent nonequilibrium probability flux in the particle position. We investigate position fluctuations associated with this nonequilibrium flux analytically and through simulation. We introduce a model which reproduces the nonequilibrium effects, and in which the magnitude of additional position fluctuations can be calculated in closed form. The ratio of additional nonconservative fluctuations to direct thermal fluctuations scales inversely with the square root of trap power, and is small for typical experimental parameters. In a simulated biophysical experiment the nonconservative scattering force does not significantly increase the observed fluctuations in the length of a double stranded DNA tether. PMID- 22060330 TI - Relaxation properties in a diffusive model of k-mers with constrained movements on a triangular lattice. AB - We study the relaxation process in a two-dimensional lattice gas model, based on the concept of geometrical frustration. In this model the particles are k-mers that can both randomly translate and rotate on the planar triangular lattice. In the absence of rotation, the diffusion of hard-core particles in crossed single file systems is investigated. We monitor, for different densities, several quantities: mean-square displacement, the self-part of the van Hove correlation function, and the self-intermediate scattering function. We observe a considerable slowing of diffusion on a long-time scale when suppressing the rotational motion of k-mers; our system is subdiffusive at intermediate times between the initial transient and the long-time diffusive regime. We show that the self-part of the van Hove correlation function exhibits, as a function of particle displacement, a stretched exponential decay at intermediate times. The self-intermediate scattering function (SISF), displaying slower than exponential relaxation, suggests the existence of heterogeneous dynamics. For each value of density, the SISF is well described by the Kohlrausch-Williams-Watts law; the characteristic timescale tau(q(n)) is found to decrease with the wave vector q(n) according to a simple power law. Furthermore, the slowing of the dynamics with density rho(0) is consistent with the scaling law 1/tau(q(n);rho(0))?(rho(c) rho(0))(kappa), with the same exponent kappa=3.34+/-0.12 for all wave vectors q(n). The density rho(c) is approximately equal to the closest packing limit, theta(CPL)?1, for dimers on the two-dimensional triangular lattice. The self diffusion coefficient D(s) scales with the same power-law exponent and critical density. PMID- 22060331 TI - Hamiltonian of mean force for damped quantum systems. AB - We consider a quantum system linearly coupled to a reservoir of harmonic oscillators. For finite coupling strengths, the stationary distribution of the damped system deviates from the predictions of standard thermodynamics. With the help of the quantum Hamiltonian of mean force, we quantify this deviation exactly for a harmonic oscillator and provide approximations in the limit of high and low temperatures and weak and strong couplings. Moreover, in the semiclassical regime, we use the quantum Smoluchowski equation to obtain results valid for any potential. We finally give a physical interpretation of the deviation in terms of the initial system-reservoir coupling. PMID- 22060333 TI - Statistical mechanical foundation of the peridynamic nonlocal continuum theory: energy and momentum conservation laws. AB - The purpose of this paper is to derive the energy and momentum conservation laws of the peridynamic nonlocal continuum theory using the principles of classical statistical mechanics. The peridynamic laws allow the consideration of discontinuous motion, or deformation, by relying on integral operators. These operators sum forces and power expenditures separated by a finite distance and so represent nonlocal interaction. The integral operators replace the differential divergence operators conventionally used, thereby obviating special treatment at points of discontinuity. The derivation presented employs a general multibody interatomic potential, avoiding the standard assumption of a pairwise decomposition. The integral operators are also expressed in terms of a stress tensor and heat flux vector under the assumption that these fields are differentiable, demonstrating that the classical continuum energy and momentum conservation laws are consequences of the more general peridynamic laws. An important conclusion is that nonlocal interaction is intrinsic to continuum conservation laws when derived using the principles of statistical mechanics. PMID- 22060332 TI - Time-dependent motor properties of multipedal molecular spiders. AB - Molecular spiders are synthetic biomolecular walkers that use the asymmetry resulting from cleavage of their tracks to bias the direction of their stepping motion. Using Monte Carlo simulations that implement the Gillespie algorithm, we investigate the dependence of the biased motion of molecular spiders, along with binding time and processivity, on tunable experimental parameters, such as number of legs, span between the legs, and unbinding rate of a leg from a substrate site. We find that an increase in the number of legs increases the spiders' processivity and binding time but not their mean velocity. However, we can increase the mean velocity of spiders with simultaneous tuning of the span and the unbinding rate of a spider leg from a substrate site. To study the efficiency of molecular spiders, we introduce a time-dependent expression for the thermodynamic efficiency of a molecular motor, allowing us to account for the behavior of spider populations as a function of time. Based on this definition, we find that spiders exhibit transient motor function over time scales of many hours and have a maximum efficiency on the order of 1%, weak compared to other types of molecular motors. PMID- 22060334 TI - L-hop percolation on networks with arbitrary degree distributions and its applications. AB - Site percolation has been used to help understand analytically the robustness of complex networks in the presence of random node deletion (or failure). In this paper we move a further step beyond random node deletion by considering that a node can be deleted because it is chosen or because it is within some L-hop distance of a chosen node. Using the generating functions approach, we present analytic results on the percolation threshold as well as the mean size, and size distribution, of nongiant components of complex networks under such operations. The introduction of parameter L is both conceptually interesting because it accommodates a sort of nonindependent node deletion, which is often difficult to tackle analytically, and practically interesting because it offers useful insights for cybersecurity (such as botnet defense). PMID- 22060335 TI - Condensation of an ideal gas obeying non-Abelian statistics. AB - We consider the thermodynamic geometry of an ideal non-Abelian gas. We show that, for a certain value of the fractional parameter and at the relevant maximum value of fugacity, the thermodynamic curvature has a singular point. This indicates a condensation such as Bose-Einstein condensation for non-Abelian statistics and we work out the phase transition temperature in various dimensions. PMID- 22060336 TI - Spectral measure of the harmonic oscillator with alpha-stable noise. AB - We study the coordinate-velocity couple of the harmonic oscillator with alpha stable noise. As previously shown by Sokolov et al., the distribution of this couple is bivariate alpha-stable. In this work, we determine explicitly its associated spectral measure, exhibiting directly both the non-independence and non-ellipticity of the coordinate-velocity couple. Knowledge of the spectral measure allows to analyze and quantify the deviation from ellipticity. PMID- 22060337 TI - Test of fluctuation theorems in non-Markovian open quantum systems. AB - We study fluctuation theorems for open quantum systems with a non-Markovian heat bath using the approach of quantum master equations and examine the physical quantities that appear in those fluctuation theorems. The approach of Markovian quantum master equations to the fluctuation theorems was developed by Esposito and Mukamel [Phys. Rev. E 73, 046129 (2006)]. We show that their discussion can be formally generalized to the case of a non-Markovian heat bath when the local system is linearly connected to a Gaussian heat bath with the spectrum distribution of the Drude form. We found by numerically simulating the spin-boson model in non-Markovian regime that the "detailed balance" condition is well satisfied except in a strongly nonequilibrium transient situation, and hence our generalization of the definition of the "entropy production" is almost always legitimate. Therefore, our generalization of the fluctuation theorem seems meaningful in wide regions. PMID- 22060338 TI - Exit probability in a one-dimensional nonlinear q-voter model. AB - We formulate and investigate the nonlinear q-voter model (which as a special case includes the linear voter and the Sznajd model) on a one-dimensional lattice. We derive an analytical formula for the exit probability and show that it agrees perfectly with Monte Carlo simulations. The puzzle that we deal with here may be summarized by a simple question: Why does the mean-field approach give the exact formula for the exit probability in the one-dimensional nonlinear q-voter model? To answer this question, we test several hypotheses proposed recently for the Sznajd model, including the finite size effects, the influence of the range of interactions, and the importance of the initial step of the evolution. On the one hand, our work is part of a trend of the current debate on the form of the exit probability in the one-dimensional Sznajd model, but on the other hand, it concerns the much broader problem of the nonlinear q-voter model. PMID- 22060339 TI - Quantum Smoluchowski equation for a spin bath. AB - We derive the quantum mechanical description of overdamped Brownian motion of a particle in a spin bath of two-level atoms. The resulting Smoluchowski equation is used to calculate the rate of escape of the particle from a metastable state. At 0 K the decay rate is finite. We show that while quantization enhances the decay rate, higher temperatures induce thermal saturation, resulting in effective a reduction of the system-bath coupling. The role of coherence is examined. PMID- 22060340 TI - Noisy classical field theories with two coupled fields: dependence of escape rates on relative field stiffness. AB - Exit times for stochastic Ginzburg-Landau classical field theories with two or more coupled classical fields depend on the interval length on which the fields are defined, the potential in which the fields deterministically evolve, and the relative stiffness of the fields themselves. The latter is of particular importance in that physical applications will generally require different relative stiffnesses, but the effect of varying field stiffnesses has not heretofore been studied. In this paper, we explore the complete phase diagram of escape times as they depend on the various problem parameters. In addition to finding a transition in escape rates as the relative stiffness varies, we also observe a critical slowing down of the string method algorithm as criticality is approached. PMID- 22060341 TI - Percolation on correlated random networks. AB - We consider a class of random, weighted networks, obtained through a redefinition of patterns in an Hopfield-like model, and, by performing percolation processes, we get information about topology and resilience properties of the networks themselves. Given the weighted nature of the graphs, different kinds of bond percolation can be studied: stochastic (deleting links randomly) and deterministic (deleting links based on rank weights), each mimicking a different physical process. The evolution of the network is accordingly different, as evidenced by the behavior of the largest component size and of the distribution of cluster sizes. In particular, we can derive that weak ties are crucial in order to maintain the graph connected and that, when they are the most prone to failure, the giant component typically shrinks without abruptly breaking apart; these results have been recently evidenced in several kinds of social networks. PMID- 22060342 TI - Hyperbolic disordered ensembles of random matrices. AB - Using the recently introduced simple procedure of dividing Gaussian matrices by a positive random variable, a family of random matrices is generated characterized by a behavior ruled by the generalized hyperbolic distribution. The spectral density evolves from the semicircle law to a Gaussian-like behavior while concomitantly, the local fluctuations show a transition from the Wigner-Dyson to the Poisson statistics. Long range statistics such as number variance exhibit large fluctuations typical of nonergodic ensembles. PMID- 22060343 TI - Multiresonance of energy transport and absence of heat pump in a force-driven lattice. AB - Energy transport control in low dimensional nanoscale systems has attracted much attention in recent years. In this paper, we investigate the energy transport properties of the Frenkel-Kontorova lattice subject to a periodic driving force, in particular, the resonance behavior of the energy current by varying the external driving frequency. It is discovered that, in certain parameter ranges, multiple resonance peaks, instead of a single resonance, emerge. By comparing the nonlinear lattice model with a harmonic chain, we unravel the underlying physical mechanism for such a resonance phenomenon. Other parameter dependencies of the resonance behavior are examined as well. Finally, we demonstrate that heat pumping is actually absent in this force-driven model. PMID- 22060344 TI - Critical excitation spectrum of a quantum chain with a local three-spin coupling. AB - Using the phenomenological renormalization group (PRG), we evaluate the low energy excitation spectrum along the critical line of a quantum spin chain having a local interaction between three Ising spins and longitudinal and transverse magnetic fields, i.e., a Turban model. The low-energy excitation spectrum found with the PRG agrees with the spectrum predicted for the (D(4),A(4)) conformal minimal model under a nontrivial correspondence between translations at the critical line and discrete lattice translations. Under this correspondence, the measurements confirm a prediction that the critical line of this quantum spin chain and the critical point of the two-dimensional three-state Potts model are in the same universality class. PMID- 22060345 TI - Probability distribution of the time-averaged mean-square displacement of a Gaussian process. AB - We study the probability distribution of the time-averaged mean-square displacement of a discrete Gaussian process. An empirical approximation for the probability density is suggested and numerically validated for fractional Brownian motion. The optimality of quadratic forms for inferring dynamical and microrheological quantities from individual random trajectories is discussed, with emphasis on a reliable interpretation of single-particle tracking experiments. PMID- 22060346 TI - Multiterm solution of a generalized Boltzmann kinetic equation for electron and positron transport in structured and soft condensed matter. AB - In this paper, we generalize the semiclassical Boltzmann kinetic equation for dilute gases to consider highly nonequilibrium electrons and positrons in soft condensed matter, accounting rigorously for all types of interactions, including positronium formation, and allowing for both coherent and incoherent scattering processes. The limitations inherent in the seminal paper of Cohen and Lekner [M. H. Cohen and J. Lekner, Phys. Rev. 158, 305 (1967); Y. Sakai, J. Phys. D 40, R441 (2007)] are avoided by solving the kinetic equation using a "multiterm" spherical harmonic representation of the velocity distribution function, as well as formulating a necessarily nonperturbative treatment of nonconservative collisional processes such as positronium formation. Numerical calculations of transport properties are carried out for a Percus-Yevick model of a hard-sphere system, and for positrons in liquid argon. New phenomena are predicted, including structure-induced negative conductivity and anisotropic diffusion. PMID- 22060347 TI - Noise effects in a finite-size Ising-like model. AB - We study finite-size effects on properties of stationary state and also transient process of a bistable system with long range interaction. We adopt an Ising-like model with infinite range interaction (Husimi-Temperlay model). In particular, we formulate this problem in light of the Langevin equation and investigate study the effects of various types of noises. We study characteristics of the probability of stationary state of a finite system and find that there exist two types of regions in the ordered state: the saturated region in which the maximum of the distribution locates at the maximum value of the Ising variable (+/-1) and the transient region in which the maximum of the distribution locates at a nonsaturated value. We introduce an additional type of noise that represents fluctuation due to direct coupling to the thermal bath. Finally we also study the finite-size effects on the dynamical aspect by studying the mean first-passage times. PMID- 22060348 TI - Boltzmann equations for a binary one-dimensional ideal gas. AB - We consider a time-reversal invariant dynamical model of a binary ideal gas of N molecules in one spatial dimension. By making time-asymmetric assumptions about the behavior of the gas, we derive Boltzmann and anti-Boltzmann equations that describe the evolution of the single-molecule velocity distribution functions for an ensemble of such systems. We show that for a special class of initial states of the ensemble one can obtain an exact expression for the N-molecule velocity distribution function, and we use this expression to rigorously prove that the time-asymmetric assumptions needed to derive the Boltzmann and anti-Boltzmann equations hold in the limit of large N. Our results clarify some subtle issues regarding the origin of the time asymmetry of Boltzmann's H theorem. PMID- 22060349 TI - Instability of the mean-field states and generalization of phase separation in long-range interacting systems. AB - Equilibrium properties of long-range interacting systems on lattices are investigated. There was a conjecture by Cannas et al. [Phys. Rev. B 61, 11521 (2000)] that the mean-field theory is exact for spin systems with nonadditive long-range interactions. This is called "exactness of the mean-field theory." We show that the exactness of the mean-field theory holds for systems on a lattice with nonadditive two-body long-range interactions in the canonical ensemble with unfixed order parameters. We also show that in a canonical ensemble with fixed order parameters, exactness of the mean-field theory does not hold in one parameter region, which we call the "non-mean-field region." In the non-mean field region, an inhomogeneous configuration appears, in contrast to the uniform configuration in the region where the mean-field theory holds. This inhomogeneous configuration is not the one given by the standard phase separation. Therefore, the mean-field picture is not adequate to describe these states. We discuss phase transitions between the mean-field region and the non-mean-field region. Exactness of the mean-field theory in spin glasses is also discussed. PMID- 22060350 TI - Simulating the time-dependent diffusion coefficient in mixed-pore-size materials. AB - Porous media with a wide distribution of pore sizes are quite common. We show that variable-step-size random walk simulations can be used to model the time dependent diffusion coefficient D(t) in such porous media. The issue to be overcome is that, in variable-step-size walks, each walker carries its own "clock," and its position is known only at a random set of times. Thus, a direct ensemble-average calculation of (the mean-square distance traveled at time t) is problematic. We introduce a sequence of approximations that overcome this apparent difficulty. Calculations are carried out on periodic systems that contain pores of quite different sizes. Where possible, our results are compared to those obtained using fixed-step-size random walks. PMID- 22060351 TI - Anomalous negative differential thermal resistance in a momentum-conserving lattice. AB - A two-segment Fermi-Pasta-Ulam lattice has been investigated by using nonequilibrium molecular dynamics. Here we present an anomalous negative differential thermal resistance (NDTR) that has not been reported in Frenkel Kontorova and phi(4) lattices up to the present. The NDTR disappears in the low temperature region. The region of NDTR shifts from the large to the small temperature difference region as the system size increases. The anomalous dependence of NDTR on the temperature can be explained as the negative effect induced by the nonlinear coupling. The explanation can also cover the phenomenon of NDTR in momentum-nonconserved lattices. PMID- 22060352 TI - Statistics of interfacial fluctuations of radially growing clusters. AB - The dynamics of fluctuating radially growing interfaces is approached using the formalism of stochastic growth equations on growing domains. This framework reveals a number of dynamic features arising during surface growth. For fast growth, dilution, which spatially reorders the incoming matter, is responsible for the transmission of correlations. Its effects include the erasing of memory with respect to the initial condition, a partial attenuation of geometrically originated instabilities, and the restoration of universality in some special cases in which the critical exponents depend on the parameters of the equation of motion. In this sense, dilution rends the dynamics more similar to the usual one of planar systems. This fast growth regime is also characterized by the spatial decorrelation of the interface, which, in the case of radially growing interfaces, naturally originates rapid roughening and scale-dependent fractality, and suggests the advent of a self-similar fractal dimension. The center-of-mass fluctuations of growing clusters are also studied, and our analysis suggests the possible nonapplicability of usual scalings to the long-range surface fluctuations of the radial Eden model. In fact, our study points to the fact that this model belongs to a dilution-free universality class. PMID- 22060353 TI - Scaling behavior of a square-lattice Ising model with competing interactions in a uniform field. AB - Transfer-matrix methods, with the help of finite-size scaling and conformal invariance concepts, are used to investigate the critical behavior of two dimensional square-lattice Ising spin-1/2 systems with first- and second-neighbor interactions, both antiferromagnetic, in a uniform external field. On the critical curve separating collinearly ordered and paramagnetic phases, our estimates of the conformal anomaly c are very close to unity, indicating the presence of continuously varying exponents. This is confirmed by direct calculations, which also lend support to a weak-universality picture; however, small but consistent deviations from the Ising-like values eta=1/4, gamma/nu=7/4, beta/nu=1/8 are found. For higher fields, on the line separating row-shifted (2*2) and disordered phases, we find values of the exponent eta very close to zero. PMID- 22060354 TI - Frequency-dependent dispersion in porous media. AB - Several studies have shown that the performance of different chemical processes can be improved by means of periodic operation. An accurate modeling and simulation of these processes requires accounting for the dependence of the system parameters with the operating frequency. This work uses the method of volume averaging to study the behavior of dispersion with frequency (i.e., dynamic dispersion) in homogeneous porous media. In the absence of convection, the dynamic dispersion is reduced to the dynamic diffusivity, showing a decreasing behavior with frequency. In contrast, the dynamic dispersion can be either an increasing or decreasing function of frequency, depending on the particle Peclet number values. At sufficiently high frequency values, the dispersion coefficient approaches the molecular diffusivity. Comparisons with direct numerical simulations for idealized porous medium models evidence the extents and limitations of the upscaling approach. PMID- 22060355 TI - Constitutive relations for steady, dense granular flows. AB - This work focuses on the mechanical response of dry granular materials under steady, simple shear conditions. In particular, the goal is to obtain a complete rheology able to describe the material behavior within the entire range of concentrations for which the flow can be considered dense. The total stress is assumed to be the linear sum of a frictional and a kinetic component. The frictional and the kinetic contributions are modeled in the context of the critical state theory and the kinetic theory of dense granular gases, respectively; in the latter, the correlated motion among the particles, which is likely to occur at high concentration, is also included. In accordance with recent findings on disordered granular packings, the frictional component of stresses is assumed to vanish when the concentration is below the random loose packing. According to this approach, four nondimensional quantities govern steady, simple shear flows: the concentration, the shear to normal stress ratio, the ratio of the time scales associated with the motion perpendicular and parallel to the flow, and the ratio between the particle stiffness and the normal stress. The present theory allows us to reproduce, in a notable way, both numerical simulations on simple shear flows of disks and physical experiments on incline flows of glass spheres taken from the literature. PMID- 22060356 TI - Cooling rates and energy partition in inhomogeneous fluidized granular mixtures. AB - The local cooling rates of the components of a vibrated binary granular mixture in a steady state are investigated. The accuracy of the expression obtained by assuming a local homogeneous cooling state distribution of the gas is analyzed by comparing it with molecular dynamics simulation results. A good agreement is observed. Also, the profiles of the partial temperatures are compared with the theoretical prediction following from the application of the Chapman-Enskog method to solve the kinetic Enskog equations of the mixture. In this case, the agreement is satisfactory if the boundary layers near the walls are excluded. The implications of the results are discussed. PMID- 22060357 TI - Extended hard-sphere model and collisions of cohesive particles. AB - In two earlier papers the present authors modified a standard hard-sphere particle-wall and particle-particle collision model to account for the presence of adhesive or cohesive interaction between the colliding particles: the problem is of importance for modeling particle-fluid flow using the Lagrangian approach. This technique, which involves a direct numerical simulation of such flows, is gaining increasing popularity for simulating, e.g., dust transport, flows of nanofluids and grains in planetary rings. The main objective of the previous papers was to formally extend the impulse-based hard-sphere model, while suggestions for quantifications of the adhesive or cohesive interaction were made. This present paper gives an improved quantification of the adhesive and cohesive interactions for use in the extended hard-sphere model for cases where the surfaces of the colliding bodies are "dry," e.g., there is no liquid-bridge formation between the colliding bodies. This quantification is based on the Johnson-Kendall-Roberts (JKR) analysis of collision dynamics but includes, in addition, dissipative forces using a soft-sphere modeling technique. In this way the cohesive impulse, required for the hard-sphere model, is calculated together with other parameters, namely the collision duration and the restitution coefficient. Finally a dimensional analysis technique is applied to fit an analytical expression to the results for the cohesive impulse that can be used in the extended hard-sphere model. At the end of the paper we show some simulation results in order to illustrate the model. PMID- 22060358 TI - Abrasion of yardangs. AB - A model for the collision between a sand grain and a body of yardang material is established by using the principles of classical mechanics. A new nondimensional parameter, the "abrasion number" A(n), is derived from the model. The volume removed per impact for different targets is proportional to A(n) approximately. As an indicator of the energy ratio of the impacting material to the target material, A(n) not only reflects the previous "abrasion law" but also introduces two dominant mechanical parameters, Young's modulus and yield stress. We propose A(n) to be a similarity criterion for abrasion experiments. The practicability of the model under natural conditions is examined by an example. It is concluded that the abrasion rates of yardangs in the western Qaidam basin, China, are 0.011 0.398 mm/yr in the period of 1986 to 2010 and remarkable abrasion events generally correspond with strong wind conditions. The model will be helpful for reconstructing the history of aeolian activities from the morphologies of yardangs in the arid regions on Mars. PMID- 22060359 TI - Slow dynamics and precursors of the glass transition in granular fluids. AB - We use event driven simulations to analyze glassy dynamics as a function of density and energy dissipation in a two-dimensional bidisperse granular fluid under stationary conditions. Clear signatures of a glass transition are identified, such as an increase of relaxation times over several orders of magnitude. As the inelasticity is increased, the glass transition is shifted to higher densities, and the precursors of the transition become less and less pronounced, in agreement with a recent mode-coupling theory. We analyze the long time tails of the velocity autocorrelation and discuss its consequences for the nonexistence of the diffusion constant in two dimensions. PMID- 22060360 TI - Tailoring the frictional properties of granular media. AB - A method of modifying the roughness of soda-lime glass spheres is presented, with the purpose of tuning interparticle friction. The effect of chemical etching on the surface topography and the bulk frictional properties of grains are systematically investigated. The surface roughness of the grains is measured using white-light interferometry and characterized by the lateral and vertical roughness length scales. The underwater angle of repose is measured to characterize the bulk frictional behavior. We observe that the coefficient of friction depends on the vertical roughness length scale. PMID- 22060361 TI - Fluctuating hydrodynamics in a vertically vibrated granular fluid with gravity. AB - We investigate hydrodynamic fluctuations in a two-dimensional granular fluid excited by a vibrating base and in the presence of gravity, focusing on the transverse velocity modes. Since the system is inhomogeneous, we measure fluctuations in horizontal layers whose width is smaller than the characteristic hydrodynamic lengths: they can be considered as almost-homogeneous subsystems. The large time decay of the autocorrelations of modes is exponential and compatible with vorticity diffusion due to shear viscosity, as in equilibrium fluids. The velocity structure factor, which strongly deviates from the equilibrium constant behavior, is well reproduced by an effective fluctuating hydrodynamics described by two noise terms: the first associated with vorticity diffusion and the second with the local energy exchange, which have internal and external character, respectively. PMID- 22060362 TI - Hydrodynamics of a vibrated granular monolayer. AB - We investigate the long-standing puzzle of phase separation in a granular monolayer vibrated from below. Although this system is three dimensional, an interesting dynamics occurs mostly in the horizontal plane, perpendicular to the direction of vibration. Experiments [Olafsen and Urbach, Phys. Rev. Lett. 81, 4369 (1998)] demonstrated that for a high amplitude of vibration the system is in the gaslike phase, but when the amplitude becomes smaller than a certain threshold, a phase separation occurs: A solidlike dense condensate of particles forms in the center of the system, surrounded by particles in the gaslike phase. We explain theoretically the experimentally observed coexistence of dilute and dense phases, employing Navier-Stokes granular hydrodynamics. We show that the phase separation is associated with a negative compressibility of granular gas. PMID- 22060363 TI - Fluctuations of grains inside a discharging two-dimensional silo. AB - We present experimental data corresponding to a two-dimensional dense granular flow, namely, the gravity-driven discharge of grains from a small opening in a silo. We study the local velocity field at the scale of single grains at different places with the help of particle-tracking techniques. From these data, the velocity profiles can be obtained and the validity of some long-standing approaches can be assessed. Moreover, the fluctuations of the velocities are taken into consideration to characterize the features of the advective motion (due to the gravity force) and the diffusive motion, which shows nontrivial behavior. PMID- 22060364 TI - Coarse-grained dynamics of the freely cooling granular gas in one dimension. AB - We study the dynamics and structure of clusters in the inhomogeneous clustered regime of a freely cooling granular gas of point particles in one dimension. The coefficient of restitution is modeled as r(0)<1 or 1, depending on whether the relative speed is greater or smaller than a velocity scale delta. The effective fragmentation rate of a cluster is shown to rise sharply beyond a delta-dependent time scale. This crossover is coincident with the velocity fluctuations within a cluster becoming order delta. Beyond this crossover time, the cluster-size distribution develops a nontrivial power-law distribution, whose scaling properties are related to those of the velocity fluctuations. We argue that these underlying features are responsible for the recently observed nontrivial coarsening behavior in the one-dimensional freely cooling granular gas. PMID- 22060365 TI - Capillary interactions in Pickering emulsions. AB - The effective capillary interaction potentials for small colloidal particles trapped at the surface of liquid droplets are calculated analytically. Pair potentials between capillary monopoles and dipoles, corresponding to particles floating on a droplet with a fixed center of mass and subjected to external forces and torques, respectively, exhibit a repulsion at large angular separations and an attraction at smaller separations, with the latter resembling the typical behavior for flat interfaces. This change of character is not observed for quadrupoles, corresponding to free particles on a mechanically isolated droplet. The analytical results are compared with the numerical minimization of the surface free energy of the droplet in the presence of spherical or ellipsoidal particles. PMID- 22060366 TI - Anisotropy of magnetic emulsions induced by magnetic and electric fields. AB - The anisotropy of magnetic emulsions induced by simultaneously acting electric and magnetic fields is theoretically and experimentally investigated. Due to the anisotropy, the electric conductivity and magnetic permeability of a magnetic emulsion are no longer scalar coefficients, but are tensors. The electric conductivity and magnetic permeability tensors of sufficiently diluted emulsions in sufficiently weak electric and magnetic fields are found as functions of the electric and magnetic intensity vectors. The theoretically predicted induced anisotropy was verified experimentally. The experimental data are fitted in order to calculate the dimensions of the ellipsoidal drops of the emulsion distorted by the electric and magnetic fields. The dependence of the calculated fitting parameter on the intensity of the magnetic field is compared with the theoretical one. The results of the analysis of the experimental data are discussed. PMID- 22060367 TI - Impact of spherical projectiles into a viscoplastic fluid. AB - We study the behavior of a yield-stress fluid following the impact of a vertically falling sphere. Since the impact produces shear stresses larger than the yield stress, the material in the vicinity of the impact becomes fluidized. The sphere entrains air when it enters the fluid, and the resulting cavity pinches off below the surface. The upper part of this cavity then rebounds upward. For sufficiently fast impacts, a vertical jet is produced by the cavity collapse. While many aspects of this process are similar to that in Newtonian fluids or granular materials, the rheological properties of our target material change the scaling of the cavity pinch-off depth and have a dramatic effect on the height of the jets. The material returns to a solid-like behavior once the stresses due to the impact have relaxed to below the yield stress, leaving a crater in the surface of the material. We find that the diameter of this crater depends nonmonotonically on the impact speed. The crater shape also changes with speed, reflecting the dynamics of the impact process. PMID- 22060368 TI - Dynamic self-assembly and directed flow of rotating colloids in microchannels. AB - Nonequilibrium structure formation and dynamics in suspensions of superparamagnetic colloids driven by an external rotating magnetic field are studied by particle-based mesoscale hydrodynamics simulations in confined geometry. We address the fundamental question how the rotation of the colloids about their own axes can be converted into a translational motion by breaking the symmetry of the confining geometry. We study a two-dimensional system of colloids with short-range repulsive interactions, which mimics flow in shallow microchannels. In straight channels, we observe a two-way traffic but--for symmetry reasons--no net transport. However, by keeping some colloids fixed near one of the two walls, net transport can be achieved. This approach allows the control and switchability of the flow in complex microchannel networks. A minimal geometry that fulfills the requirement of broken symmetry are ring channels. We determine the translational velocity of the spinning colloids and study its dependence on the channel width for various median radii. We conclude that spinning colloids present a promising alternative for flow generation and control in microfluidic devices. PMID- 22060369 TI - Influence of an ellipsoid on the angular order in a two-dimensional cluster. AB - The influence of an ellipsoid on the angular order of two-dimensional classical clusters is investigated through Brownian dynamics simulations. We found the following: (1) The presence of an ellipsoid does not influence the start of the angular melting, but reduces the rate at which the inner rings can rotate with respect to each other. (2) Even a small eccentricity of the ellipsoid leads to a stabilization of the angular order of the system. (3) Depending on the position of the ellipsoid in the cluster, a reentrant behavior in the angular order is observed before full radial melting of the cluster sets in. (4) The ellipsoid can lead to a two-step angular melting process: First, the rotation of the inner rings with respect to each other is hindered by the ellipsoid, but on further increasing the kinetic energy of the system, the ellipsoid just starts to behave as a spherical particle with different mobility. The effect of an ellipsoid on the molten system does not depend crucially on the interparticle interaction, but a softer parabolic confinement reduces the angular stabilization. PMID- 22060370 TI - Evaporation of solutions and colloidal dispersions in confined droplets. AB - We present a model that describes the drying of solutions and colloidal dispersions from droplets confined between two circular plates. This confined geometry, proposed by Clement and Leng [Langmuir 20, 6538 (2004)], casts a perfect control of the evaporation conditions, and thus also of the concentration kinetics of the solutes in the droplet. Our model, based on simple transport equations for binary mixtures, describes the concentration process of the solute inside the droplet. Using dimensionless units, we identify the different numbers that govern the concentration field of the solute, and we detail how to extract kinetic and thermodynamic information on the binary mixture from such drying experiments. We finally discuss, using numerical resolution of the model and analytical arguments, several specific cases: dilute solutions, a colloidal hard sphere dispersion, and a binary molecular mixture. PMID- 22060371 TI - Systematic modification of the rheological properties of colloidal suspensions with polyelectrolyte multilayers. AB - Tailoring rheological properties of colloidal suspensions with the adsorption of polyelectrolyte multilayers (PEMs) is based on the idea of controlling macroscopic mechanical properties by modifying the particle surface in a reproducible and well-understood manner. With layer-by-layer self-assembly, monodisperse polystyrene particles are coated with up to ten layers of the oppositely charged strong polyelectrolytes: poly(diallyl dimethyl ammonium chloride) and poly(styrene sulfonate). The conformation of the adsorbed polyelectrolyte is controlled by the ionic strength of the used aqueous polyelectrolyte solution. For 1M NaCl solution, a brushlike adsorption of the polyelectrolyte is expected. The ability of PEMs to serve on a nanoscale level as surface modifiers and influence macroscopic rheological properties like viscoelasticity, yield stress, and shear banding is discussed. The mechanical behavior of these suspensions is qualitatively described by the theory of Derjaguin-Landau-Verwey-Overbeek with short-range repulsion and long-range attraction. A scaling rule is proposed which distinguishes between the precusor and the multilayer regime. PMID- 22060372 TI - Shear thickening and jamming in densely packed suspensions of different particle shapes. AB - We investigated the effects of particle shape on shear thickening in densely packed suspensions. Rods of different aspect ratios and nonconvex hooked rods were fabricated. Viscosity curves and normal stresses were measured using a rheometer for a wide range of packing fractions for each shape. Suspensions of each shape exhibit qualitatively similar discontinuous shear thickening. The logarithmic slope of the stress vs shear rate increases dramatically with packing fraction and diverges at a critical packing fraction phi(c) which depends on particle shape. The packing fraction dependence of the viscosity curves for different convex shapes can be collapsed when the packing fraction is normalized by phi(c). Intriguingly, viscosity curves for nonconvex particles do not collapse on the same set as convex particles, showing strong shear thickening over a wider range of packing fraction. The value of phi(c) is found to coincide with the onset of a yield stress at the jamming transition, suggesting the jamming transition also controls shear thickening. The yield stress is found to correspond with trapped air in the suspensions, and the scale of the stress can be attributed to interfacial tension forces which dramatically increase above phi(c) due to the geometric constraints of jamming. Using this connection we show that the jamming transition can be identified by simply looking at the surface of suspensions. The relationship between shear and normal stresses is found to be linear in both the shear thickening and jammed regimes, indicating that the shear stresses come from friction. In the limit of zero shear rate, normal stresses pull the rheometer plates together due to the surface tension of the liquid below phi(c), but push the rheometer plates apart due to jamming above phi(c). PMID- 22060373 TI - Dynamic rheology of a supercooled polymer melt in nonuniform oscillating flows between rapidly oscillating plates. AB - The dynamic rheology of a polymer melt composed of short chains with ten beads between rapidly oscillating plates is investigated for various oscillation frequencies by using the hybrid simulation of the molecular dynamics and computational fluid dynamics. In the quiescent state, the melt is in a supercooled state, and the stress relaxation function G(t) exhibits a stretched exponential relaxation on the time scale of the alpha relaxation time tau(alpha) (the structural relaxation of beads) and then follows the Rouse relaxation function characterized by the Rouse relaxation time tau(R) (the conformational relaxation of polymer chains). In the rapidly oscillating plates, nonuniform boundary layer flows are generated over the plate due to inertia of the fluid, and the local rheological properties of the melt are spatially varied according to the local flow fields. The local strain and local strain rate of the melt monotonically decrease with the distance from the plate at each oscillation frequency of the plate, but their dependencies on the oscillation frequency at a fixed distance from the plate vary with the distance. Far from the plate, the local strain decreases as the oscillation frequency increases such that the dynamic rheology deviates from the linear moduli at the low oscillation frequencies rather than high oscillation frequencies. On the contrary, near the plate, the local strain rate increases with the oscillation frequency such that the shear thinning is enhanced at high oscillation frequencies. In close vicinity to the plate, the dynamic viscosity is mostly independent of the oscillation frequency, and the shear thinning behavior becomes similar to that observed in steady shear flows. We show the diagram of the loss tangent of the melt for different oscillation frequencies and local strain rates. It is seen that the melt generates three different rheological regimes, i.e., the viscous fluid regime, liquidlike viscoelastic regime, and solidlike viscoelastic regime, according to the oscillation frequency and local strain rate. Nonlinear rheological properties are also investigated by the spectrum analysis and the Lissajous-Bowditch curve. It is found that the fractional amplitude of the higher harmonics to the linear harmonics is suppressed within the boundary layer due to the nonslip boundary on the oscillating plate. We also find that the melt exhibits intercycle shear thinning between different positions but exhibits intracycle shear thickening at a fixed position in the vicinity of the plate. PMID- 22060374 TI - Efficient encapsulation with plug-triggered drop formation. AB - Monodisperse microscale drops formed with microfluidic devices are useful for encapsulating cells, microgel particles, or even additional drops. These techniques are thus useful for applications ranging from high-throughput biology to monodisperse particle and capsule synthesis, which require encapsulation of such objects. However, it is challenging to efficiently encapsulate the objects in all drops; often, the objects are encapsulated inefficiently, resulting in many improperly filled, unusable drops. Here, we describe a phenomenon that allows very efficient encapsulation. We use the inflow of the object to plug the drop maker nozzle; the continued injection of the outer phase pinches off a drop, thereby encapsulating the object; this yields precisely one object encapsulated per drop. PMID- 22060375 TI - Molecular dynamics changes induced by solvent in 2-ethyl-1-hexanol. AB - Apart from other classes of materials, supramolecular structures may exist in H bonded liquids due to the existence of hydrogen bonding. The dynamics of these structures remains one of the most exciting topics of interest of modern science because of its crucial meaning for the behavior of water and its participation in biological processes. A special group of these liquids form monohydroxy alcohols due to their similarity to water, their ability to vitrification, and the existence of the Debye relaxation process in dielectric loss spectra reflecting the dynamics of H-bond structures. Dynamics of these structures can be studied by changes of thermodynamic conditions, by immersion of the liquid into the constraint geometry, and by dilution in a nonassociated solvent. Herein we studied the behavior of relaxation dynamics of mixtures of 2-ethyl-1-hexanol with bromobutane using broadband dielectric spectroscopy. Analysis of the results exhibits the existence of crossover in temperature dependence of static permittivity of the Debye process at some particular temperature T(c). This temperature shifts to lower values with increasing concentration of bromobutane. Moreover, below some "critical" concentration of alcohol in the mixture the shape of the Debye process loses exponentiality and the temperature dependence of relaxation times starts to change. This change was illuminated based on the analysis of the steepness index. For the lowest concentration, the value of this parameter becomes the same as the value of the steepness index of faster relaxation, called process II, of pure alcohol at ambient pressure. The observed change in relaxation dynamics with lowering concentration of alcohol is astonishingly similar to the behavior observed in the same material at elevated pressure. A possible origin of these similarities is also discussed. PMID- 22060376 TI - Wall-mass effects on hydrodynamic boundary slip. AB - This paper investigates the combined effects of surface stiffness kappa and wall particles' mass m(w) on the slip length. It aims to enhance our understanding of the momentum and energy transfer across solid-liquid interfaces. Elastic spring potentials are employed to simulate the thermal solid walls and model the surface stiffness kappa. The thermal oscillation amplitude is primarily dictated by values of stiffness, whereas the oscillating frequency is proportional to ?(kappa/m(w)). It is shown that for cases with variable wall mass the relation of slip length and thermal oscillating frequencies can be approximated by a "master" curve according to which the length initially increases, then approaches a peak value, and afterwards is reduced toward an asymptotic value. PMID- 22060377 TI - Diffusion processes in water on oxide surfaces: quasielastic neutron scattering study of hydration water in rutile nanopowder. AB - Quasielastic neutron scattering (QENS) was used to investigate the diffusion dynamics of hydration water on the surface of rutile (TiO(2)) nanopowder. The dynamics measurements utilizing two inelastic instruments, a backscattering spectrometer and a disk chopper spectrometer, probed the fast, intermediate, and slow motions of the water molecules on the time scale of picoseconds to more than a nanosecond. We employed a model-independent analysis of the data collected at each value of the scattering momentum transfer to investigate the temperature dependence of several diffusion components. All of the probed components were present in the studied temperature range of 230-320 K, providing, at a first sight, no evidence of discontinuity in the hydration water dynamics. However, a qualitative change in the elastic scattering between 240 and 250 K suggested a surface freezing-melting transition, when the motions that were localized at lower temperatures became delocalized at higher temperatures. On the basis of our previous molecular dynamics simulations of this system, we argue that interpretation of QENS data from such a complex interfacial system requires at least qualitative input from simulations, particularly when comparing results from spectrometers with very different energy resolutions and dynamic ranges. PMID- 22060378 TI - Glassy relaxation and excess wing in mode-coupling theory: the dynamic susceptibility of propylene carbonate above and below T(c). AB - We explore the possibility of describing experimental susceptibility spectra of the glass former propylene carbonate with a two-component schematic model of mode coupling theory (MCT) from above the melting point down to temperatures far below the critical temperature of MCT. By introducing a phenomenological time-dependent hopping rate, the spectra are reproduced in the full frequency and temperature range available. Literature data of dielectric susceptibilities and depolarized Brillouin light-scattering spectra are combined with our measurements of photon correlation spectroscopy to cover up to 18 decades in frequency of spectra for two different dynamical variables. A consistent description of all data sets is obtained by adjusting only a few physically motivated parameters. In particular the excess wing or slow beta-relaxation commonly observed in the susceptibility spectra can consistently be modeled as originating from a coupling of the individual experimental probe correlator to the collective density fluctuations. PMID- 22060379 TI - Unified derivation of phase-field models for alloy solidification from a grand potential functional. AB - In the literature, two quite different phase-field formulations for the problem of alloy solidification can be found. In the first, the material in the diffuse interfaces is assumed to be in an intermediate state between solid and liquid, with a unique local composition. In the second, the interface is seen as a mixture of two phases that each retain their macroscopic properties, and a separate concentration field for each phase is introduced. It is shown here that both types of models can be obtained by the standard variational procedure if a grand-potential functional is used as a starting point instead of a free energy functional. The dynamical variable is then the chemical potential instead of the composition. In this framework, a complete analogy with phase-field models for the solidification of a pure substance can be established. This analogy is then exploited to formulate quantitative phase-field models for alloys with arbitrary phase diagrams. The precision of the method is illustrated by numerical simulations with varying interface thickness. PMID- 22060380 TI - Time-dependent distributions in self-quenching nucleation. AB - Diffusion- and interface-limited Becker-Doring (BD) -type nucleation is considered in a closed system, where supersaturation is depleted by growing nuclei. Special focus is on nonadiabatic effects, which become increasingly pronounced for barriers lower than 20-25k(B)T, and which lead to nucleation rates deviating from their quasi-steady-state (QSS) values. Several essential modifications of the QSS distribution are observed. For example, the front is continuous rather than sharp and has a double-exponential shape, which is in agreement with the earlier matched asymptotic solution obtained in neglect of depletion. The total number of nuclei is larger than predicted by the QSS approximation. The obtained distributions are compared with numerical solutions of the BD equations and can serve as initial conditions for further transition to the Ostwald Ripening stage. PMID- 22060381 TI - Instabilities of soft elastic microtubes filled with viscous fluids: pearls, wrinkles, and sausage strings. AB - A linear stability analysis is presented to study the self-organized instabilities of a highly compliant elastic cylindrical shell filled with a viscous liquid and submerged in another viscous medium. The prototype closely mimics many components of micro- or nanofluidic devices and biological processes such as the budding of a string of pearls inside cells and sausage-string formation of blood vessels. The cylindrical shell is considered to be a soft linear elastic solid with small storage modulus. When the destabilizing capillary force derived from the cross-sectional curvature overcomes the stabilizing elastic and in-plane capillary forces, the microtube can spontaneously self organize into one of several possible configurations; namely, pearling, in which the viscous fluid in the core of the elastic shell breaks up into droplets; sausage strings, in which the outer interface of the mircrotube deforms more than the inner interface; and wrinkles, in which both interfaces of the thin-walled mircrotube deform in phase with small amplitudes. This study identifies the conditions for the existence of these modes and demonstrates that the ratios of the interfacial tensions at the interfaces, the viscosities, and the thickness of the microtube play crucial roles in the mode selection and the relative amplitudes of deformations at the two interfaces. The analysis also shows asymptotically that an elastic fiber submerged in a viscous liquid is unstable for Y=gamma/(G(e)R)>6 and an elastic microchannel filled with a viscous liquid should rupture to form spherical cavities (pearling) for Y>2, where gamma, G(e), and R are the surface tension, elastic shear modulus, and radius, respectively, of the fiber or microchannel. PMID- 22060382 TI - Anomalous roughening in competitive growth models with time-decreasing rates of correlated dynamics. AB - Lattice growth models where uncorrelated random deposition competes with some aggregation dynamics that generates correlations are studied with rates of the correlated component decreasing as a power law. These models have anomalous roughening, with anomalous exponents related to the normal exponents of the correlated dynamics, to an exponent characterizing the aggregation mechanism and to that power-law exponent. This is shown by a scaling approach extending the Family-Vicsek relation previously derived for the models with time-independent rates, thus providing a connection of normal and anomalous growth models. Simulation results for several models support those conclusions. Remarkable anomalous effects are observed even for slowly decreasing rates of the correlated component, which may correspond to feasible temperature changes in systems with activated dynamics. The scaling exponents of the correlated component can be obtained only from the estimates of three anomalous exponents, without knowledge of the aggregation mechanism, and a possible application is discussed. For some models, the corresponding Edwards-Wilkinson and Kardar-Parisi-Zhang equations are also discussed. PMID- 22060383 TI - Real-time studies of evaporation-induced colloidal self-assembly by optical microspectroscopy. AB - Real-time monitoring of the whole growth process of evaporation-induced colloidal self-assembly has been conducted using an optical microspectroscopy setup. Our observations suggest that the assembly process can be divided into three different growth stages as evidenced by the variations detected in the reflectance spectra. The thickness variation of the growing colloidal crystal was monitored by examining the Fabry-Perot fringes in the reflectance spectra. Furthermore, the scalar wave approximation was utilized to analyze the evolution of optical properties with growth. More detailed information, including the time dependence of number of layers and volume fraction of water, has been revealed by comparing the experimental and calculated reflectance spectra. The present work demonstrates that in situ real-time microspectroscopy is a promising technique for monitoring and investigating the dynamic process of colloidal self-assembly. PMID- 22060384 TI - Surface order at surfactant-laden interfaces between isotropic liquid crystals and liquid phases with different polarity. AB - We present an ellipsometry study of the interface between thermotropic liquid crystals and liquid phases consisting of various binary mixtures of water and glycerol. The liquid-crystal samples contain a small constant amount of a surfactant which induces a homeotropic anchoring at the interface. We determine the smectic or nematic order at the interface in the temperature range above the liquid-crystal-isotropic transition while the water to glycerol ratio is varied, corresponding to a systematic modification of the polarity of the liquid phase. The surface-induced order becomes less pronounced with increasing glycerol concentration in the liquid phase. The observed behavior is compared with previous studies in which the surfactant concentration in the liquid-crystal bulk phase was varied. The results indicate that in both cases the magnitude of the surfactant coverage at the interface is the key quantity which determines the liquid-crystal surface order at the interface. PMID- 22060385 TI - Chiral dipole induced by azimuthal anchoring on the surface of a planar elastic quadrupole. AB - A spherical colloid with the tangential surface nematic director, aligned along the surface meridians, is known as a planar elastic quadrupole. The azimuthal anchoring, however, can induce a deviation of the planar director from the meridional lines. We show that a helical component of the planar surface director at the spherical surface of a planar quadrupole removes all the reflection symmetry planes and gives rise to a chiral elastic dipolar component. Using an ansatz approach, we consider the interplay between the quadrupole and anchoring induced chiral dipole components. The chirality is enhanced by the bend-twist anisotropy. The interaction of the chiral components changes the attraction directions of two such colloids. In particular, a point appears at which the quadrupolar repulsion is balanced by the dipolar attraction. PMID- 22060386 TI - Colloidal entanglement in highly twisted chiral nematic colloids: twisted loops, Hopf links, and trefoil knots. AB - The topology and geometry of closed defect loops is studied in chiral nematic colloids with variable chirality. The colloidal particles with perpendicular surface anchoring of liquid crystalline molecules are inserted in a twisted nematic cell with the thickness that is only slightly larger than the diameter of the colloidal particle. The total twist of the chiral nematic structure in cells with parallel boundary conditions is set to 0, pi, 2pi, and 3pi, respectively. We use the laser tweezers to discern the number and the topology of the -1/2 defect loops entangling colloidal particles. For a single colloidal particle, we observe that a single defect loop is winding around the particle, with the winding pattern being more complex in cells with higher total twist. We observe that colloidal dimers and colloidal clusters are always entangled by one or several 1/2 defect loops. For colloidal pairs in pi-twisted cells, we identify at least 17 different entangled structures, some of them exhibiting linked defect loops Hopf link. Colloidal entanglement is even richer with a higher number of colloidal particles, where we observe not only linked, but also colloidal clusters knotted into the trefoil knot. The experiments are in good agreement with numerical modeling using Landau-de Gennes theory coupled with geometrical and topological considerations using the method of tetrahedral rotation. PMID- 22060387 TI - Phase behavior and properties of the liquid-crystal dimer 1'',7''-bis(4 cyanobiphenyl-4'-yl) heptane: a twist-bend nematic liquid crystal. AB - The liquid-crystal dimer 1'',7''-bis(4-cyanobiphenyl-4'-yl)heptane (CB7CB) exhibits two liquid-crystalline mesophases on cooling from the isotropic phase. The high-temperature phase is nematic; the identification and characterization of the other liquid-crystal phase is reported in this paper. It is concluded that the low-temperature mesophase of CB7CB is a new type of uniaxial nematic phase having a nonuniform director distribution composed of twist-bend deformations. The techniques of small-angle x-ray scattering, modulated differential scanning calorimetry, and dielectric spectroscopy have been applied to establish the nature of the nematic-nematic phase transition and the structural features of the twist-bend nematic phase. In addition, magnetic resonance studies (electron-spin resonance and (2)H nuclear magnetic resonance) have been used to investigate the orientational order and director distribution in the liquid-crystalline phases of CB7CB. The synthesis of a specifically deuterated sample of CB7CB is reported, and measurements showed a bifurcation of the quadrupolar splitting on entering the low-temperature mesophase from the high-temperature nematic phase. This splitting could be interpreted in terms of the chirality of the twist-bend structure of the director. Calculations using an atomistic model and the surface interaction potential with Monte Carlo sampling have been carried out to determine the conformational distribution and predict dielectric and elastic properties in the nematic phase. The former are in agreement with experimental measurements, while the latter are consistent with the formation of a twist-bend nematic phase. PMID- 22060388 TI - Smectic-A and smectic-C phases and phase transitions in 8S5 liquid-crystal aerosil gels. AB - High-resolution x-ray scattering studies of the nonpolar thermotropic liquid crystal 4-n-pentylphenylthiol-4'-n-octyloxybenzoate (8S5) in aerosil gel nanonetworks reveal that the aerosil-induced disorder significantly alters both the nematic to smectic-A and smectic-A to smectic-C phase transitions. The limiting 8S5 smectic-A correlation length follows a power-law dependence on the aerosil density in quantitative agreement with the limiting lengths measured previously in other smectic-A liquid crystal gels. The smectic-A to smectic-C liquid crystalline phase transition is altered fundamentally by the presence of the aerosil gel. The onset of the smectic-C phase remains relatively sharp but there is an extended coexistence region where smectic-A and smectic-C domains can exist. PMID- 22060389 TI - Ferroelectric behavior of orthogonal smectic phase made of bent-core molecules. AB - Ferroelectric behavior in the recently reported orthogonal ferroelectric Sm A(d)P(F) phase in an unsymmetric bent-core molecule with a carbosilane terminal group was studied. The ferroelectricity of the Sm-A(d)P(F) phase was unambiguously confirmed by optical second-harmonic generation activity in the absence of an electric field, ferroelectric response, and high dielectric strength. The long-range polar order is a consequence of weakened interlayer coupling due to the formation of carbosilane sublayers, which allows for the parallel order of dipole moments of bent-core molecules in the neighboring layers. It develops in the system gradually through the second-order phase transition from the orthogonal Sm-A(d) phase. In the Sm-A(d)P(F) phase the strong surface anchoring results in the splay of polarization across the sample thickness. The polar surface anchoring also brings about strongly thickness dependent polar fluctuations, as proved by the dielectric measurements (Goldstone like mode). The relaxation frequency and dielectric strength vary more than one order of magnitude with cell thickness; in particular the dielectric strength attains more than 2000 in a 25 MUm-thick cell and continues to increase for thicker cells. Simple theory developed qualitatively explains the experimental results, supporting the polarization splay model proposed. PMID- 22060390 TI - Depth profile of optically recorded patterns in light-sensitive liquid-crystal elastomers. AB - We investigated nonlinear absorption and photobleaching processes in a liquid crystal elastomer doped with light-sensitive azobenzene moiety. A conventional one-dimensional holographic grating was recorded in the material with the use of two crossed UV laser beams and the angular dependence of the diffraction efficiency in the vicinity of the Bragg peak was analyzed. These measurements gave information on the depth to which trans to cis isomerization had progressed into the sample as a function of the UV irradiation time. Using a numerical model that takes into account the propagation of writing beams and rate equations for the local concentration of the absorbing trans conformer, we computed the expected spatial distribution of the trans and cis conformers and the shape of the corresponding Bragg diffraction peak for different irradiation doses. Due to residual absorption of the cis conformers the depth of the recording progresses logarithmically with time and is limited by the thermal relaxation from the cis to trans conformation. PMID- 22060391 TI - Flexoelectric measurements of a bent-core nematic liquid crystal. AB - A large flexoelectric polarization might be expected for a bent-core nematic liquid crystal, due to the combination of molecular shape and transverse dipole component. In this study a bent-core nematic compound is doped to be highly chiral, and measurements of the difference in flexoelectric coefficients (e(1) e(3)) are carried out by exploiting the chiral flexoelectro-optic effect. The measured flexoelectric coefficients are greater than those for many conventional calamitic nematics, but several orders of magnitude lower than recent reports on other bent-core compounds. The influence of the bent molecular shape on the nematic phase is evident from measurements of the elastic constants, where an unusually low ratio of k(3) to k(1) indicates that bend distortions of the director are relatively lower in energy compared to those involving splay. PMID- 22060392 TI - Helical phase of chiral nematic liquid crystals as the Bianchi VII0 group manifold. AB - We show that the optical structure of the helical phase of a chiral nematic is naturally associated with the Bianchi VII(0) group manifold, of which we give a full account. The Joets-Ribotta metric governing propagation of the extraordinary rays is invariant under the simply transitive action of the universal cover E(2) of the three-dimensional Euclidean group of two dimensions. Thus extraordinary light rays are geodesics of a left-invariant metric on this Bianchi type VII(0) group. We are able to solve, by separation of variables, both the wave equation and the Hamilton-Jacobi equation for this metric. The former reduces to Mathieu's equation, and the latter to the quadrantal pendulum equation. We discuss Maxwell's equations for uniaxial optical materials where the configuration is invariant under a group action and develop a formalism to take advantage of these symmetries. The material is not assumed to be impedance matched, thus going beyond the usual scope of transformation optics. We show that for a chiral nematic in its helical phase Maxwell's equations reduce to a generalized Mathieu equation. Our results may also be relevant to helical phases of some magnetic materials and to light propagation in certain cosmological models. PMID- 22060393 TI - Glassy dynamics in the isotropic phase of a smectogenic liquid crystalline compound. AB - The temperature evolution of the primary relaxation time in the isotropic phase of 4-cyano-4'-tetradecylbiphenyl (14CB) above the isotropic-smectic A (I-SmA) transition is discussed. Based on the enthalpy space and distortion-sensitive analysis, the prevalence of the mode coupling theory (MCT) "critical" and "glassy" dynamics is shown. The obtained singular dependence is related to the MCT critical temperature located approximately 48 K below the clearing (I-SmA) temperature. However, a weak but detectable distortion in the immediate vicinity of the transition occurs. It is also shown that the value of the fragile strength coefficient D(T) is characteristic of a very fragile glassy liquid whereas the steepness index m is typical of a strong one. Both magnitudes anomalously change on approaching the I-SmA phase transition. The static permittivity shows the pretransitional effect linked to the temperature of the hypothetical continuous phase transition located approximately 10.2 K below the I-SmA transition. PMID- 22060394 TI - First-principle approach to rescale the dynamics of simulated coarse-grained macromolecular liquids. AB - We present a detailed derivation and testing of our approach to rescale the dynamics of mesoscale simulations of coarse-grained polymer melts (I. Y. Lyubimov, J. McCarty, A. Clark, and M. G. Guenza, J. Chem. Phys. 132, 224903 (2010)). Starting from the first-principle Liouville equation and applying the Mori-Zwanzig projection operator technique, we derive the generalized Langevin equations (GLEs) for the coarse-grained representations of the liquid. The chosen slow variables in the projection operators define the length scale of coarse graining. Each polymer is represented at two levels of coarse graining: monomeric as a bead-and-spring model and molecular as a soft colloid. In the long-time regime where the center-of-mass follows Brownian motion and the internal dynamics is completely relaxed, the two descriptions must be equivalent. By enforcing this formal relation we derive from the GLEs the analytical rescaling factors to be applied to dynamical data in the coarse-grained representation to recover the monomeric description. Change in entropy and change in friction are the two corrections to be accounted for to compensate the effects of coarse graining on the polymer dynamics. The solution of the memory functions in the coarse-grained representations provides the dynamical rescaling of the friction coefficient. The calculation of the internal degrees of freedom provides the correction of the change in entropy due to coarse graining. The resulting rescaling formalism is a function of the coarse-grained model and thermodynamic parameters of the system simulated. The rescaled dynamics obtained from mesoscale simulations of polyethylene, represented as soft-colloidal particles, by applying our rescaling approach shows a good agreement with data of translational diffusion measured experimentally and from simulations. The proposed method is used to predict self diffusion coefficients of new polyethylene samples. PMID- 22060395 TI - Interfacial properties of polystyrene thin films as revealed by neutron reflectivity. AB - We have studied the glass transition temperature (T(g)) and molecular mobility of polystyrene (PS) thin films near the interface between the polymer thin film and substrate with bilayer thin films consisting of surface hydrogenated PS (h-PS) and bottom deuterated PS (d-PS) using neutron reflectivity. With decreasing the thickness of the bottom d-PS layer, T(g) near the interface between the polymer thin film and substrate increased compared to bulk T(g) and a drastic increase of T(g) was observed for the bottom d-PS layer <155 A thick. The orientation of polymer chains at the interface is supposed to be related to the increase of T(g) near the interface between the polymer and substrate. The polymer chain mobility decreased with thickness even for the bottom d-PS layer with no discernible change of T(g). It is considered that the numerous contacts between polymer chains and substrate are related to the decrease of mobility near the interface between the polymer thin film and substrate. PMID- 22060396 TI - Thermodynamics of polymer adsorption to a flexible membrane. AB - We analyze the structural behavior of a single polymer chain grafted to an attractive, flexible surface. Our model is composed of a coarse-grained bead-and spring polymer and a tethered membrane. By means of extensive parallel tempering Monte Carlo simulations it is shown that the system exhibits a rich phase behavior ranging from highly ordered, compact to extended random coil structures, and from desorbed to completely adsorbed or even partially embedded conformations. These findings are summarized in a pseudophase diagram indicating the predominant class of conformations as a function of the external parameters temperature and polymer-membrane interaction strength. By comparison with adsorption to a stiff membrane surface it is shown that the flexibility of the membrane gives rise to qualitatively new behavior such as stretching of adsorbed conformations. PMID- 22060397 TI - Moran model as a dynamical process on networks and its implications for neutral speciation. AB - In population genetics, the Moran model describes the neutral evolution of a biallelic gene in a population of haploid individuals subjected to mutations. We show in this paper that this model can be mapped into an influence dynamical process on networks subjected to external influences. The panmictic case considered by Moran corresponds to fully connected networks and can be completely solved in terms of hypergeometric functions. Other types of networks correspond to structured populations, for which approximate solutions are also available. This approach to the classic Moran model leads to a relation between regular networks based on spatial grids and the mechanism of isolation by distance. We discuss the consequences of this connection for topopatric speciation and the theory of neutral speciation and biodiversity. We show that the effect of mutations in structured populations, where individuals can mate only with neighbors, is greatly enhanced with respect to the panmictic case. If mating is further constrained by genetic proximity between individuals, a balance of opposing tendencies takes place: increasing diversity promoted by enhanced effective mutations versus decreasing diversity promoted by similarity between mates. Resolution of large enough opposing tendencies occurs through speciation via pattern formation. We derive an explicit expression that indicates when speciation is possible involving the parameters characterizing the population. We also show that the time to speciation is greatly reduced in comparison with the panmictic case. PMID- 22060398 TI - Dynamical singularities in adaptive delayed-feedback control. AB - We demonstrate the dynamical characteristics of adaptive delayed-feedback control systems, exploiting a discrete-time adaptive control method derived for carrying out detailed analysis. In particular, the systems exhibit singularities such as power-law decay of the distribution of transient times and almost zero finite time Lyapunov exponents. We can explain these results by characterizing such systems as having (1) a Jacobian matrix with unity eigenvalue in the whole phase space, and (2) parameters approaching a stability boundary proven to be identical with that of (nonadaptive) delayed-feedback control. PMID- 22060399 TI - Dynamics of a genetic toggle switch at the nucleotide and codon levels. AB - We study the dynamics of a model stochastic two-gene switch at the nucleotide and codon levels. First, we show that its stability, the mean lifetime of the noisy attractors, differs from that of a model where transcription and translation elongation are modeled as single-step delayed events, indicating the need of detailed models to study the dynamics of switches. Next, we vary the coupling between the two genes by varying the affinity of repressor proteins to the promoters and measure the mutual information between the two proteins times series. We find that there is a degree of coupling that maximizes information propagation between the two genes. This is explained by the effects of the coupling on mean and entropy of RNA and protein numbers of each gene, as well as correlation, 2-tuple entropy between the two proteins numbers, and, finally, the stability of the noisy attractors. We also find that increasing the rate of translation initiation increases the correlation between RNA and protein numbers and between the two proteins, due to increased stability of the noisy attractors. Increasing the rate of transcription or decreasing RNA degradation causes opposite effects to the correlation between RNA and proteins of each gene and the stability of the noisy attractors. Finally, we add a sequence-dependent transcription pause site and show that both its probability of occurrence, as well as its mean time length, affects the dynamics of the switch, further demonstrating the dependence of the dynamics of this circuit on sequence level events. PMID- 22060400 TI - Correlated heterogeneous deformation of entangled fiber networks. AB - We study the deformation of a network of entangled non-cross-linked semiflexible fibers subjected to compression. We show that the deformation is intermittent, heterogeneous, and dominated by the occurrence of avalanches. Avalanches imply relative fiber sliding and rearrangement and lead to a serrated stress-strain curve. A large fraction of the fibers in the system contribute to an avalanche, and the amplitudes of the sliding events are correlated spatially. This phenomenon is qualitatively similar in systems with and without friction between fibers and is not due to frictional stick slip. PMID- 22060401 TI - Shear unzipping of double-stranded DNA. AB - We use a simple nonlinear scaler displacement model to calculate the distribution of effects created by a shear stress on a double-stranded DNA (dsDNA) molecule and the value of shear force F(c) that is required to separate the two strands of a molecule at a given temperature. It is shown that for molecules of base pairs fewer than than 21, the entire single strand moves in the direction of applied force, whereas for molecules having base pairs more than 21, part of the strand moves in the opposite direction under the influence of force acting on the other strand. This result as well as the calculated values of F(c) as a function of length of dsDNA molecules are in very good agreement with the experimental values of Hatch et al. [Phys. Rev. E 78, 011920 (2008)]. PMID- 22060402 TI - Effects of surface hydrophobicity on the conformational changes of polypeptides of different length. AB - We studied the effects of surface hydrophobicity on the conformational changes of different length polypeptides by calculating the free energy difference between peptide structures using the bias-potential Monte Carlo technique and the probability ratio method. It was found that the hydrophobic surface plays an important role in the stability of secondary structures of the polypeptides with hydrophobic side chains. For short GAAAAG peptides, the hydrophobic surface destabilizes the alpha helix but stabilizes the beta hairpin in the entire temperature region considered in our study. Interestingly, when the surface hydrophobic strength epsilon(hpsf)>=epsilon(hp), the most stable structure in the low temperature region changes from alpha helix to beta hairpin, and the corresponding phase transition temperature increases slightly. For longer GAAAAAAAAAAG peptides, the effects of the relatively weak hydrophobic surface (epsilon(hpsf) < epsilon(hp)) on alpha-helical structures may be neglected, while the relatively strongly hydrophobic surface (epsilon(hpsf)>=epsilon(hp)) leads to the obvious partial helicity loss. In contrast, the stability of beta structures can be enhanced significantly by the hydrophobic surface, especially by the strongly hydrophobic surface, at low and intermediate temperatures. At high temperatures, in addition to thermal fluctuations, the strongly hydrophobic surface (epsilon(hpsf)>epsilon(hp)) may further disturb the formation of both alpha-helical and beta structures. Moreover, the phase transition temperature between alpha-helical structures and random coils significantly decreases due to the helicity loss when epsilon(hpsf)>epsilon(hp). Our findings provide a basic and quantitative picture for understanding the effects of a hydrophobic surface on the conformational changes of the polypeptides with hydrophobic side chains. From an application viewpoint, the present study is helpful in developing alternative strategies of producing high-quality biological fibrillar materials and functional nanoscale devices by the self-assembly of the polypeptides on hydrophobic surfaces. PMID- 22060403 TI - Fixation, transient landscape, and diffusion dilemma in stochastic evolutionary game dynamics. AB - Agent-based stochastic models for finite populations have recently received much attention in the game theory of evolutionary dynamics. Both the ultimate fixation and the pre-fixation transient behavior are important to a full understanding of the dynamics. In this paper, we study the transient dynamics of the well-mixed Moran process through constructing a landscape function. It is shown that the landscape playing a central theoretical "device" that integrates several lines of inquiries: the stable behavior of the replicator dynamics, the long-time fixation, and continuous diffusion approximation associated with asymptotically large population. Several issues relating to the transient dynamics are discussed: (i) multiple time scales phenomenon associated with intra- and inter attractoral dynamics; (ii) discontinuous transition in stochastically stationary process akin to Maxwell construction in equilibrium statistical physics; and (iii) the dilemma diffusion approximation facing as a continuous approximation of the discrete evolutionary dynamics. It is found that rare events with exponentially small probabilities, corresponding to the uphill movements and barrier crossing in the landscape with multiple wells that are made possible by strong nonlinear dynamics, plays an important role in understanding the origin of the complexity in evolutionary, nonlinear biological systems. PMID- 22060404 TI - Event-driven simulations of a plastic, spiking neural network. AB - We consider a fully connected network of leaky integrate-and-fire neurons with spike-timing-dependent plasticity. The plasticity is controlled by a parameter representing the expected weight of a synapse between neurons that are firing randomly with the same mean frequency. For low values of the plasticity parameter, the activities of the system are dominated by noise, while large values of the plasticity parameter lead to self-sustaining activity in the network. We perform event-driven simulations on finite-size networks with up to 128 neurons to find the stationary synaptic weight conformations for different values of the plasticity parameter. In both the low- and high-activity regimes, the synaptic weights are narrowly distributed around the plasticity parameter value consistent with the predictions of mean-field theory. However, the distribution broadens in the transition region between the two regimes, representing emergent network structures. Using a pseudophysical approach for visualization, we show that the emergent structures are of "path" or "hub" type, observed at different values of the plasticity parameter in the transition region. PMID- 22060405 TI - Phase transitions and spatially ordered counterion association in ionic-lipid membranes: a statistical model. AB - We propose a statistical model to account for the gel-fluid anomalous phase transitions in charged bilayer- or lamellae-forming ionic lipids. The model Hamiltonian comprises effective attractive interactions to describe neutral-lipid membranes as well as the effect of electrostatic repulsions of the discrete ionic charges on the lipid headgroups. The latter can be counterion dissociated (charged) or counterion associated (neutral), while the lipid acyl chains may be in gel (low-temperature or high-lateral-pressure) or fluid (high-temperature or low-lateral-pressure) states. The system is modeled as a lattice gas with two distinct particle types--each one associated, respectively, with the polar headgroup and the acyl-chain states--which can be mapped onto an Ashkin-Teller model with the inclusion of cubic terms. The model displays a rich thermodynamic behavior in terms of the chemical potential of counterions (related to added salt concentration) and lateral pressure. In particular, we show the existence of semidissociated thermodynamic phases related to the onset of charge order in the system. This type of order stems from spatially ordered counterion association to the lipid headgroups, in which charged and neutral lipids alternate in a checkerboard-like order. Within the mean-field approximation, we predict that the acyl-chain order-disorder transition is discontinuous, with the first-order line ending at a critical point, as in the neutral case. Moreover, the charge order gives rise to continuous transitions, with the associated second-order lines joining the aforementioned first-order line at critical end points. We explore the thermodynamic behavior of some physical quantities, like the specific heat at constant lateral pressure and the degree of ionization, associated with the fraction of charged lipid headgroups. PMID- 22060406 TI - Simple biophysical model of tumor evasion from immune system control. AB - The competitive nonlinear interplay between a tumor and the host's immune system is not only very complex but is also time-changing. A fundamental aspect of this issue is the ability of the tumor to slowly carry out processes that gradually allow it to become less harmed and less susceptible to recognition by the immune system effectors. Here we propose a simple epigenetic escape mechanism that adaptively depends on the interactions per time unit between cells of the two systems. From a biological point of view, our model is based on the concept that a tumor cell that has survived an encounter with a cytotoxic T-lymphocyte (CTL) has an information gain that it transmits to the other cells of the neoplasm. The consequence of this information increase is a decrease in both the probabilities of being killed and of being recognized by a CTL. We show that the mathematical model of this mechanism is formally equal to an evolutionary imitation game dynamics. Numerical simulations of transitory phases complement the theoretical analysis. Implications of the interplay between the above mechanisms and the delivery of immunotherapies are also illustrated. PMID- 22060407 TI - Profile structures of the voltage-sensor domain and the voltage-gated K(+) channel vectorially oriented in a single phospholipid bilayer membrane at the solid-vapor and solid-liquid interfaces determined by x-ray interferometry. AB - One subunit of the prokaryotic voltage-gated potassium ion channel from Aeropyrum pernix (KvAP) is comprised of six transmembrane alpha helices, of which S1-S4 form the voltage-sensor domain (VSD) and S5 and S6 contribute to the pore domain (PD) of the functional homotetramer. However, the mechanism of electromechanical coupling interconverting the closed-to-open (i.e., nonconducting-to-K(+) conducting) states remains undetermined. Here, we have vectorially oriented the detergent (OG)-solubilized VSD in single monolayers by two independent approaches, namely "directed-assembly" and "self-assembly," to achieve a high in plane density. Both utilize Ni coordination chemistry to tether the protein to an alkylated inorganic surface via its C-terminal His_{6} tag. Subsequently, the detergent is replaced by phospholipid (POPC) via exchange, intended to reconstitute a phospholipid bilayer environment for the protein. X-ray interferometry, in which interference with a multilayer reference structure is used to both enhance and phase the specular x-ray reflectivity from the tethered single membrane, was used to determine directly the electron density profile structures of the VSD protein solvated by detergent versus phospholipid, and with either a moist He (moderate hydration) or bulk aqueous buffer (high hydration) environment to preserve a native structure conformation. Difference electron density profiles, with respect to the multilayer substrate itself, for the VSD-OG monolayer and VSD-POPC membranes at both the solid-vapor and solid-liquid interfaces, reveal the profile structures of the VSD protein dominating these profiles and further indicate a successful reconstitution of a lipid bilayer environment. The self-assembly approach was similarly extended to the intact full length KvAP channel for comparison. The spatial extent and asymmetry in the profile structures of both proteins confirm their unidirectional vectorial orientation within the reconstituted membrane and indicate retention of the protein's folded three-dimensional tertiary structure upon completion of membrane bilayer reconstitution. Moreover, the resulting high in-plane density of vectorially oriented protein within a fully hydrated single phospholipid bilayer membrane at the solid-liquid interface will enable investigation of their conformational states as a function of the transmembrane electric potential. PMID- 22060408 TI - Bubble statistics and positioning in superhelically stressed DNA. AB - We present a general framework to study the thermodynamic denaturation of double stranded DNA under superhelical stress. We report calculations of position- and size-dependent opening probabilities for bubbles along the sequence. Our results are obtained from transfer-matrix solutions of the Zimm-Bragg model for unconstrained DNA and of a self-consistent linearization of the Benham model for superhelical DNA. The numerical efficiency of our method allows for the analysis of entire genomes and of random sequences of corresponding length (10(6)-10(9) base pairs). We show that, at physiological conditions, opening in superhelical DNA is strongly cooperative with average bubble sizes of 10(2)-10(3) base pairs (bp), and orders of magnitude higher than in unconstrained DNA. In heterogeneous sequences, the mean degree of base-pair opening is self-averaging, while bubble localization and statistics are dominated by sequence disorder. Compared to random sequences with identical GC-content, genomic DNA has a significantly increased probability to open large bubbles under superhelical stress. These bubbles are frequently located directly upstream of transcription start sites. PMID- 22060409 TI - Bistability induces episodic spike communication by inhibitory neurons in neuronal networks. AB - Bistability is one of the important features of nonlinear dynamical systems. In neurodynamics, bistability has been found in basic Hodgkin-Huxley equations describing the cell membrane dynamics. When the neuron is clamped near its threshold, the stable rest potential may coexist with the stable limit cycle describing periodic spiking. However, this effect is often neglected in network computations where the neurons are typically reduced to threshold firing units (e.g., integrate-and-fire models). We found that the bistability may induce spike communication by inhibitory coupled neurons in the spiking network. The communication is realized in the form of episodic discharges with synchronous (correlated) spikes during the episodes. A spiking phase map is constructed to describe the synchronization and to estimate basic spike phase locking modes. PMID- 22060410 TI - Objective method for estimating asymptotic parameters, with an application to sequence alignment. AB - Sequence alignment is an indispensable computational tool in modern molecular biology. The model underlying biological sequence alignment is of interest to physicists because it approximates the statistical mechanics of DNA and protein annealing, while bearing an intimate relationship to models of directed polymers in random media. Recent methods for determining the statistics of random sequence alignments have reduced the computation time to less than 1 s, opening up some interesting possibilities for online computation with biological search engines. Before implementation, however, the methods required an objective technique for computing regression coefficients pertinent to an asymptotic regime. Typically, physicists estimate parameters pertinent to an asymptotic regime subjectively: They eyeball their data; estimate the asymptotic regime where the regression model holds with reasonable accuracy; and then regress data only within the estimated asymptotic regime. Our publicly available computer program ARRP replaces the subjective assessment of the asymptotic regime with an objective change-point detection method, increasing confidence in the scientific objectivity of the parameter estimates. Asymptotic regression has potential applications across most of physics. PMID- 22060411 TI - Ecological oscillations induced by a shared predator and the "Winner peaks first" rule. AB - We investigate the dynamics of an ecological system made up of one predator feeding on two different prey species. In a large range of parameter space, the system displays oscillating solutions. We show that, in the regime in which the two preys coexist, the better fit prey consistently peaks first. Further, we classify the possible oscillations of the network by a symbolic dynamics method. Our findings show that the symbolic orbits of an ecological system contain information about which of two preys is the better fit, and when one is bound to extinction. PMID- 22060412 TI - Phase-noise-induced resonance in a single neuronal system. AB - Phase-disorder-induced resonance has been recently uncovered in an ensemble of coupled excitable neurons with weak external signal, where each neuron takes a constant initial signal phase [Phys. Rev. E 82, 010902(R) (2010)]. However, it is unclear how the initial phase disorder influences the behavior of a single or isolated neuron, which constitutes the ensemble. In order to answer this question, we here consider the case of a single neuron with phase noise originated from the time-varying initial signal phase, in contrast to the constant initial phase in each neuron studied in the above referenced paper. Interestingly, we find that the phase noise can induce resonance even in the single neuronal system with subthreshold signal. Moreover, we reveal that, with the presence of phase noise, the neuron also shows another resonance behavior by varying the period of the external signal. An analysis is conducted to uncover the mechanisms behind these resonance phenomena. PMID- 22060413 TI - Partial hydrodynamic screening of confined linear and circular double-stranded DNA dynamics. AB - We performed experiments and simulations to investigate the influence of hydrodynamic interaction on the diffusion dynamics of circular and linear lambda DNA confined in nanoslits. Contrary to the common assumption that intrachain hydrodynamic interaction (HI) is completely screened when polymers are confined in channels with height h smaller than the radius of gyration R(g), it is found that the HI is partially screened and approaches complete screening only for R(g)?h. For lambda-DNA, the HI becomes nearly completely screened only when the channel height is smaller than the Kuhn length. In addition, the dynamics of linear and circular lambda-DNA in very strong confinement is shown to be independent of the chain topology. PMID- 22060414 TI - Multifractal analysis of thermal denaturation based on the Peyrard-Bishop-Dauxois model. AB - The theory of DNA dynamics is exceedingly complex and not easily explained. In the past two decades, by adapting methods of statistical physics, the dynamics of DNA in contact with a thermal bath is widely studied. In this paper, the thermal denaturation of DNA in the framework of the Peyrard-Bishop-Dauxois (PBD) model through the Renyi dimension is investigated. As a result, the Renyi dimension spectrum of the melting transition process reveals the multifractal nature of the dynamics of the Peyrard-Bishop-Dauxois model. Also, it can be concluded that the Renyi dimension (D(q)) at negative values of q is the characteristic signature of pre-melting and thermal denaturation of DNA. Furthermore, this approach is in excellent agreement with previous experimental studies. PMID- 22060415 TI - Charged bilayer membranes in asymmetric ionic solutions: phase diagrams and critical behavior. AB - We consider the phase separation in an asymmetrically charged lipid bilayer membrane consisting of neutral and negatively charged lipids that are in contact with in and out ionic solutions having different ionic strengths. The two asymmetric leaflets are coupled through electrostatic interactions. Based on a free-energy approach, the critical point and phase diagrams are calculated for different ionic strengths of the two solutions and coupling parameter. An increase of the coupling constant or asymmetry in the salt concentration between the in and out solutions yields a higher phase-separation temperature because of electrostatic interactions. As a consequence, the phase-coexistence region increases for strong screening (small Debye length). Finally, possible three phase coexistence regions in the phase diagram are predicted. PMID- 22060416 TI - Measuring absolute number concentrations of nanoparticles using single-particle tracking. AB - Single-particle tracking (SPT) microscopy is increasingly used to characterize nanoparticulate systems. We introduce a concept for estimation of particle number concentration in Brownian particle dispersions using SPT based on a model for the trajectory length distribution of particles to estimate the detection region volume. The resulting method is independent of precalibration reference measurements, and robust with respect to image processing settings. Experimentally estimated concentrations of different dilutions of 0.19- and 0.52 MUm polymer nanospheres are in excellent agreement with estimates computed from the concentrations of the stock solutions. PMID- 22060417 TI - Bidirectional transport in a multispecies totally asymmetric exclusion-process model. AB - We study a minimal lattice model which describes bidirectional transport of "particles" driven along a one-dimensional track, as is observed in microtubule based, motor protein driven bidirectional transport of cargo vesicles, lipid bodies, and organelles such as mitochondria. This minimal model, a multispecies totally asymmetric exclusion process (TASEP) with directional switching, can provide a framework for understanding the interplay between the switching dynamics of individual particles and the collective movement of particles in one dimension. When switching is much faster than translocation, the steady-state density and current profiles of the particles are homogeneous in the bulk and are well described by mean-field (MF) theory, as determined by comparison to a Monte Carlo simulation. In this limit, we can map this model to the exactly solvable partially asymmetric exclusion-process (PASEP) model. Away from this fast switching regime the MF theory fails, although the average bulk density profile still remains homogeneous. We study the steady-state behavior as a function of the ratio of the translocation and net switching rates Q and find a unique first order phase transition at a finite Q associated with a discontinuous change of the bulk density. When the switching rate is decreased further (keeping translocation rate fixed), the system approaches a jammed phase with a net current that tends to zero as J~1/Q. We numerically construct the phase diagram for finite Q. PMID- 22060418 TI - Tuning the performance of an artificial protein motor. AB - The Tumbleweed (TW) is a concept for an artificial, tri-pedal, protein-based motor designed to move unidirectionally along a linear track by a diffusive tumbling motion. Artificial motors offer the unique opportunity to explore how motor performance depends on design details in a way that is open to experimental investigation. Prior studies have shown that TW's ability to complete many successive steps can be critically dependent on the motor's diffusional step time. Here, we present a simulation study targeted at determining how to minimize the diffusional step time of the TW motor as a function of two particular design choices: nonspecific motor-track interactions and molecular flexibility. We determine an optimal nonspecific interaction strength and establish a set of criteria for optimal molecular flexibility as a function of the nonspecific interaction. We discuss our results in the context of similarities to biological, linear stepping diffusive molecular motors with the aim of identifying general engineering principles for protein motors. PMID- 22060419 TI - Hierarchical organization of brain functional networks during visual tasks. AB - The functional network of the brain is known to demonstrate modular structure over different hierarchical scales. In this paper, we systematically investigated the hierarchical modular organizations of the brain functional networks that are derived from the extent of phase synchronization among high-resolution EEG time series during a visual task. In particular, we compare the modular structure of the functional network from EEG channels with that of the anatomical parcellation of the brain cortex. Our results show that the modular architectures of brain functional networks correspond well to those from the anatomical structures over different levels of hierarchy. Most importantly, we find that the consistency between the modular structures of the functional network and the anatomical network becomes more pronounced in terms of vision, sensory, vision-temporal, motor cortices during the visual task, which implies that the strong modularity in these areas forms the functional basis for the visual task. The structure function relationship further reveals that the phase synchronization of EEG time series in the same anatomical group is much stronger than that of EEG time series from different anatomical groups during the task and that the hierarchical organization of functional brain network may be a consequence of functional segmentation of the brain cortex. PMID- 22060420 TI - Fluid transport by active elastic membranes. AB - A flexible membrane deforming its shape in time can self-propel in a viscous fluid. Alternatively, if the membrane is anchored, its deformation will lead to fluid transport. Past work in this area focused on situations where the deformation kinematics of the membrane were prescribed. Here we consider models where the deformation of the membrane is not prescribed, but instead the membrane is internally forced. Both the time-varying membrane shape and the resulting fluid motion result then from a balance between prescribed internal active stresses, internal passive resistance, and external viscous stresses. We introduce two specific models for such active internal forcing: one where a distribution of active bending moments is prescribed, and one where active inclusions exert normal stresses on the membrane by pumping fluid through it. In each case, we asymptotically calculate the membrane shape and the fluid transport velocities for small forcing amplitudes, and recover our results using scaling analysis. PMID- 22060421 TI - Effect of robustness on selection of a mutation-rate regulating gene. AB - We study the evolution of a population of sequences, where each sequence is divided into a reproduction-rate (fitness) encoding part and a mutation-rate regulating part. Evolutionary selection acts on the sequence both by a direct fitness landscape and by indirect selection on a mutation landscape through which the sequence's mutation rate is determined, thereby providing a model of a mutation-rate-regulating gene. Coupling of the fitness landscape and mutation landscape leads to adaptive evolution of the sequence. We investigate the effects of robustness in the mutation landscape and fitness landscapes on selection of the sequence. We find that the effects of robustness in both the mutation and the fitness landscape can be described by an effective sequence length, defined as the mutational load divided by the per-base mutation rate, and we give expressions for the effective sequence length for various fitness and mutation landscapes. The probability that the sequence with a reduced mutation rate evolves is increased by increasing the robustness of the mutation landscape, and decreased by increasing the robustness of the fitness landscape. However, in the case of the mutation-rate-regulating part making up only a very small part of the total sequence length, we show that selection for a more robust sequence with less-reduced mutation rate is very weak, and therefore we conjecture that robust sequences play little role in selection of error-reducing mechanisms in real populations. PMID- 22060422 TI - Estimation of the bending rigidity and spontaneous curvature of fluid membranes in simulations. AB - Several numerical methods for measuring the bending rigidity and the spontaneous curvature of fluid membranes are studied using two types of meshless membrane models. The bending rigidity is estimated from the thermal undulations of planar and tubular membranes and the axial force of tubular membranes. We found a large dependence of its estimate value from the thermal undulation analysis on the upper-cutoff frequency q(cut) of the least-squares fit. The inverse power spectrum fit with an extrapolation to q(cut)->0 yields the smallest estimation error among the investigated methods. The spontaneous curvature is estimated from the axial force of tubular membranes and the average curvature of bent membrane strips. The results of these methods show good agreement with each other. PMID- 22060423 TI - Cell sorting based on motility differences. AB - Self-propelled particles are used to simulate cell aggregates in a model considering homogeneous adhesion forces between cells and using only motility differences as segregation drivers. The tendency of cells to follow their neighbors is also included in the formulation. Three model variants are explored, and the conditions on which motility differences may produce segregation are mapped in parameter diagrams. The evolution of the order parameter measuring cell segregation is similar to those found by models based on differential adhesion. It is also found that, considering only velocity differences, the faster cells envelope the slower ones, which is opposite to the ordering observed in early experiments by Jones and co-workers [Jones, Evans, and Lee, Exp. Cell. Res. 180, 287 (1989)]. PMID- 22060424 TI - Bubble solitons in an inhomogeneous, helical DNA molecular chain with flexible strands. AB - Base pair opening in an inhomogeneous, DNA double helical molecular chain with flexible strands is investigated by studying its internal dynamics. For the study, a generalized model which takes into account the energies involved in stacking and hydrogen bonds along with inhomogeneity, helicity, and phonons coupled to the stacking and hydrogen bonds is proposed. The internal dynamics of the proposed DNA model is governed by a perturbed nonlinear Schrodinger equation. The unperturbed, completely integrable nonlinear Schrodinger equation which admits soliton solutions and forming a bubble corresponds to DNA dynamics with homogeneous and rigid strands. The results of the soliton perturbation analysis show that the inhomogeneity in stacking and hydrogen bonds in localized and periodic forms and the helicity do not alter the amplitude under perturbation. However, the flexibility of the strands diminishes the perturbed amplitude. On the other hand, the velocity of the soliton and bubble are unaltered due to all the above effects. However, the position and phase of the soliton and the bubble vary linearly in time. While the position of the soliton depends on the initial velocity, the phase depends on both the initial velocity and the initial amplitude of the soliton. The above effects introduce small fluctuation in the tail of the soliton, without affecting the robust nature of the soliton and the bubble during propagation. The soliton and the bubble obtained as solutions of the internal dynamics of the DNA molecule represent an opening of the base pairs which is essential for the transcription process. PMID- 22060425 TI - Network analysis reveals cross-links of the immune pathways activated by bacteria and allergen. AB - Many biological networks are characterized by directed edges that represent either activating (positive) or inhibiting (negative) regulation. Most graph theoretical methods used to study biological networks either disregard this important feature, or study the role of edge sign only in the context of small subgraphs called motifs. Here, we develop path-based measures which capture, on continuous scales spanning negative and positive values, both the long- and short range regulatory relationships among node pairs. These measures also allow the quantification of each node's overall influence on the whole network and its susceptibility to regulation by the rest of the network. We apply the measures to a network representation of the mammalian immune response to simultaneous attack by allergen and respiratory bacteria. Although allergen and bacteria elicit different immune pathways, there is significant overlap (cross-talk) and feedback between these pathways. We identify key immune components in this cross-talk; particularly revealing the importance of natural killer cells as a key regulatory target in the cross-talk. PMID- 22060426 TI - Shearing self-propelled suspensions: arrest of coarsening and suppression of giant density fluctuations. AB - We study the effect of a linear shear flow on a collection of interacting active, self-propelled particles modeled via the Vicsek model. The imposed flow has a dramatic effect on the behavior of the model. We find that in the presence of shear there is no order-disorder transition, and that coarsening of the domains is arrested. Shear also suppresses the so-called giant density fluctuations that are observed in the quiescent limit. PMID- 22060427 TI - Marginal stability in chemical systems and its relevance in the origin of life. AB - Concentration fluctuations are always present in solutions; it has been noticed that, in chemical systems, they can lead to deviations from what is expected from mass-action equations. I recently described the class of the "marginally stable" chemical systems; namely, a system that have an infinity of stationary states forming a continuous curve, and I showed that they present such deviations, which appear as a drift along the stationary-state curve [Phys. Rev. Lett. 105, 058102 (2010)]. Here I describe various marginally stable chemical reaction networks, including replicating molecules, and I present numerical calculations based on reaction-diffusion master equations, showing that the thermodynamic fluctuations induce a drift. This drift can be interpreted in terms of evolution toward a more efficiently replicating system and is analogous to a Darwinian evolution. The concentration fluctuations observed during the drift are scale invariant. Relevance of this phenomenon to the origin of life is discussed. I propose that marginal stability is the mathematical property defining chemical reaction networks potentially involved in the origin of life. PMID- 22060428 TI - Short-time evolution in the adaptive immune system. AB - We exploit a simple model to numerically and analytically investigate the effect of enforcing a time constraint for achieving a system-wide goal during an evolutionary dynamics. This situation is relevant to finding antibody specificities in the adaptive immune response as well as to artificial situations in which an evolutionary dynamics is used to generate a desired capability in a limited number of generations. When the likelihood of finding the target phenotype is low, we find that the optimal mutation rate can exceed the error threshold, in contrast to conventional evolutionary dynamics. We also show how a logarithmic correction to the usual inverse scaling of population size with mutation rate arises. Implications for natural and artificial evolutionary situations are discussed. PMID- 22060429 TI - Coarse-grained mechanochemical model for simulating the dynamic behavior of microtubules. AB - Modeling the structure and mechanics of microtubules, which play significant roles in various physiological functions of cells, has long been a fascinating issue. In this paper, a coarse-grained mechanochemical model is presented to study the mechanical-chemical coupling and dynamic attributes of microtubules. The interactions among tubulins are taken into account from the molecular basis. This model is used to characterize the conformations of sheet-ended microtubules, to analyze the distributions of interaction energy, and further to simulate the radial indentation process of a microtubule. This method also works for investigating the dynamic properties of microtubules, e.g., their assembly, growth, deformation, and structural evolution for different conditions. This study is helpful for understanding the structure-mechanics-function relationship of microtubules and lays a foundation for further investigation of their dynamic behavior. PMID- 22060430 TI - Protein-folding simulations of the hydrophobic-hydrophilic model by combining pull moves with energy landscape paving. AB - The energy landscape paving (ELP) method is a class of heuristic global optimization algorithms based on Monte Carlo sampling. By incorporating the generation of an initial conformation based on a greedy strategy, the conformation update mechanism based on pull moves, and some heuristic off-trap strategies into an improved ELP method, we propose an alternative version of the ELP method, called the ELP-pull move method. We test the ELP-pull move method on both two-dimensional (2D) and 3D hydrophobic-hydrophilic protein-folding models. For ten 2D benchmark sequences of length ranging from 20 to 100, the proposed algorithm finds the lowest energies so far. Within the achieved results, the algorithm converges more rapidly and efficiently than previous methods. For all ten 3D sequences with a length of 64, the ELP-pull move method finds lower energies within comparable computational times. The numerical results demonstrate that our algorithm is a powerful method to study the lattice protein-folding model. PMID- 22060431 TI - Renewal theory of coupled neuronal pools: stable states and slow trajectories. AB - A theory is provided to analyze the dynamics of delay-coupled pools of spiking neurons based on stability analysis of stationary firing. Transitions between stable and unstable regimes can be predicted by bifurcation analysis of the underlying integral dynamics. Close to the bifurcation point the network exhibits slowly changing activities and allows for slow collective phenomena like continuous attractors. PMID- 22060432 TI - Role of fluctuations in membrane models: thermal versus nonthermal. AB - We study the comparative importance of thermal to nonthermal fluctuations for membrane-based models in the linear regime. Our results, both in 1+1 and 2+1 dimensions, suggest that nonthermal fluctuations dominate thermal ones only when the relaxation time tau is large. For moderate to small values of tau, the dynamics is defined by a competition between these two forces. The results are expected to act as a quantitative benchmark for biological modeling in systems involving cytoskeletal and other nonthermal fluctuations. PMID- 22060433 TI - Generalized interacting self-avoiding trails on the square lattice: phase diagram and critical behavior. AB - A generalized model for interacting self-avoiding trails on a square lattice is presented and studied using numerical transfer matrix methods. The model differentiates between on-site double visits corresponding to collisions, and crossings. Rigidity is also included in the model. The model includes the Nienhuis O(n=0) model and the interacting self-avoiding trail model as special cases. It is shown that the generic type of collapse found is the same as in the pure interacting self-avoiding trail model. PMID- 22060434 TI - Ising model on a hyperbolic plane with a boundary. AB - A hyperbolic plane can be modeled by a structure called the enhanced binary tree. We study the ferromagnetic Ising model on top of the enhanced binary tree using the renormalization-group analysis in combination with transfer-matrix calculations. We find a reasonable agreement with Monte Carlo calculations on the transition point, and the resulting critical exponents suggest the mean-field surface critical behavior. PMID- 22060435 TI - Separability of electrostatic and hydrodynamic forces in particle electrophoresis. AB - By use of optical tweezers we explicitly measure the electrostatic and hydrodynamic forces that determine the electrophoretic mobility of a charged colloidal particle. We test the ansatz of O'Brien and White [J. Chem. Soc. Faraday II 74, 1607 (1978)] that the electrostatically and hydrodynamically coupled electrophoresis problem is separable into two simpler problems: (1) a particle held fixed in an applied electric field with no flow field and (2) a particle held fixed in a flow field with no applied electric field. For a system in the Helmholtz-Smoluchowski and Debye-Huckel regimes, we find that the electrostatic and hydrodynamic forces measured independently accurately predict the electrophoretic mobility within our measurement precision of 7%; the O'Brien and White ansatz holds under the conditions of our experiment. PMID- 22060436 TI - X-ray-induced water vaporization. AB - We present quantitative evidence for x-ray-induced water vaporization: water is vaporized at a rate of 5.5 pL/s with the 1-A-wavelength x-ray irradiation of ~0.1 photons per A(2); moreover, water vapor is reversibly condensed during pauses in irradiation. This result fundamentally suggests that photoionization induces vaporization. This phenomenon is attributed to surface-tension reduction by ionization and would be universally important in radiological and electrohydrodynamic situations. PMID- 22060437 TI - Role of chain entropy in an analytic model of protein binding in single-DNA stretching experiments. AB - We show that the simple analytical model proposed by Zhang and Marko [Phys. Rev. E 77, 031916 (2008)] to illustrate Maxwell relations for single-DNA experiments can be improved by including the zero-force entropy of a Gaussian chain. The resulting model is in excellent agreement with the discrete persistent-chain model and is in a form convenient for analyzing experimental data. PMID- 22060438 TI - Wavelet analysis of corneal endothelial electrical potential difference reveals cyclic operation of the secretory mechanism. AB - The corneal endothelium is a fluid-transporting epithelium. As other similar tissues, it displays an electrical potential of ~1 mV (aqueous side negative) across the entire layer [transendothelial potential difference (TEPD)]. It appears that this electrical potential is mainly the result of the transport of anions across the cell layer (from stroma to aqueous). There is substantial evidence that the TEPD is related linearly to fluid transport; hence, under proper conditions, its measure could serve as a measure of fluid transport. Furthermore, the TEPD is not steady; instead, it displays a spectrum of frequency components (0-15 Hz) recognized recently using Fourier transforms. Such frequency components appear due to charge-separating (electrogenic) processes mediated by epithelial plasma membrane proteins (both ionic channels and ionic cotransporters). In particular, the endothelial TEPD oscillations of the highest amplitude (1-2 Hz) were linked to the operation of so-called sodium bicarbonate cotransporters. However, no time localization of that activity could be obtained with the Fourier methodology utilized. For that reason we now characterize the TEPD using wavelet analysis with the aim to localize in time the variations in TEPD. We find that the mentioned high-amplitude oscillatory components of the TEPD appear cyclically during the several hours that an endothelial preparation survives in vitro. They have a period of 4.6 +/- 0.4 s on average (n=4). The wavelet power value at the peak of such oscillations is 1.5 +/- 0.1 mV(2) Hz on average (n = 4), and is remarkably narrow in its distribution. PMID- 22060439 TI - Effect of shear force on the separation of double-stranded DNA. AB - Using the Langevin dynamics simulation, we have studied the effects of shear force on the rupture of short double-stranded DNA at different temperatures. We show that the rupture force increases linearly with chain length and approaches the asymptotic value in accordance with the experiment. The qualitative nature of these curves remains almost the same for different temperatures but with a shift in the force. We observe three different regimes in the extension of covalent bonds (backbone) under shear force. PMID- 22060440 TI - Minimal fragmentation problem. AB - As an alternative to the paradigmatic fragmentation problem of a single object crushed into a great number of pieces, we survey a large collection of identical bodies, each one randomly split into two fragments only. While some key features of usual fragmentation are preserved, this minimal approach allows for closed analytical results on both shape abundances and mass distributions for the fragments, with robust power-law regimes. All the results are compared to numerical simulations. PMID- 22060441 TI - Global organization of spiral structures in biparameter space of dissipative systems with Shilnikov saddle-foci. AB - We reveal and give a theoretical explanation for spiral-like structures of periodicity hubs in the biparameter space of a generic dissipative system. We show that organizing centers for "shrimp"-shaped connection regions in the spiral structure are due to the existence of Shilnikov homoclinics near a codimension-2 bifurcation of saddle-foci. PMID- 22060442 TI - Whispering gallery modes formed by partial barriers in ultrasmall deformed microdisks. AB - Unexpected formation of regular high-Q whispering gallery modes in a deformed microdisk where the radius is of the order of the vacuum wavelength is explained in terms of partial barriers in phase space. Using a semiclassical approach to determine the action flux of the partial barriers, we successfully predict spectral ranges in which the high-Q modes can exist. Our analysis enables optimization of emission directionality and the Q factor of deformed ultrasmall microcavities. PMID- 22060443 TI - Symmetry breaking between statistically equivalent, independent channels in few channel chaotic scattering. AB - We study the distribution function P(omega) of the random variable omega=tau(1)/(tau(1)+...+tau(N)), where tau(k)'s are the partial Wigner delay times for chaotic scattering in a disordered system with N independent, statistically equivalent channels. In this case, tau(k)'s are independent and identically distributed random variables with a distribution Psi(tau) characterized by a "fat" power-law intermediate tail ~1/tau(1+MU), truncated by an exponential (or a log-normal) function of tau. For N=2 and N=3, we observe a surprisingly rich behavior of P(omega), revealing a breakdown of the symmetry between identical independent channels. For N=2, numerical simulations of the quasi-one-dimensional Anderson model confirm our findings. PMID- 22060444 TI - Taylor cones in a leaky dielectric liquid under an ac electric field. AB - Conical points of a leaky dielectric drop surrounded by a dielectric gas in an external ac electric field are investigated. A novel class of steady conical tips depending on the permittivity ratio and applied signal frequency is presented. It is found that conical solutions with very small angles are possible (angles much smaller than the classical Taylor cone angle 49.3 degrees for a conducting drop in a dc field); this result can be relevant to the observations of small cone angles in Chetwani, Maheshwari, and Chang experiments [N. Chetwani, S. Maheshwari, and H.-C. Chang, Phys. Rev. Lett. 101, 204501 (2008)]. PMID- 22060445 TI - Combustion of hydrogen-oxygen mixture in electrochemically generated nanobubbles. AB - Ignition of exothermic chemical reactions in small volumes is considered as difficult or impossible due to the large surface-to-volume ratio. Here observation of the spontaneous reaction is reported between hydrogen and oxygen in bubbles whose diameter is smaller than a threshold value around 150 nm. The effect is attributed to high Laplace pressure and to fast dynamics in nanobubbles and is the first indication on combustion in the nanoscale. In this study the bubbles were produced by water electrolysis using successive generation of H(2) and O(2) above the same electrode with short voltage pulses in the microsecond range. The process was observed in a microsystem at current densities >1000 A/cm(2) and relative supersaturations >1000. PMID- 22060446 TI - Pouring viscous fluid out of a tipped container in minimal time. AB - Emptying a container partially filled with viscous fluid can be a frustratingly slow process. It takes time for the fluid to even begin discharging after tipping the container to develop a draining film on the interior surface. To study the effects of the shape and the tipping angle of the container, we predict the time required for the fluid to begin discharging in two simple geometries. In addition, the volume of the fluid yet to be discharged at subsequent times is predicted to decrease as t(-1/2) or t(-1) for flow driven along a plane or corner, respectively. We compare these theoretical predictions with laboratory experiments and discuss how viscous fluids could be poured out most effectively. PMID- 22060447 TI - Directed percolation describes lifetime and growth of turbulent puffs and slugs. AB - We show that directed percolation (DP) simulations in a pipe geometry in 3+1 dimensions capture the observed complex phenomenology of the transition to turbulence. At low Reynolds numbers (Re), turbulent puffs form and spontaneously relaminarize. At high Re, turbulent slugs expand uniformly into the laminar regions. In a spatiotemporally intermittent state between these two regimes of Re, puffs split and turbulent regions exhibit laminar patches. DP also captures some of the quantitative features of the transition, with a superexponentially diverging characteristic lifetime below the transition. Above the percolation threshold, active (turbulent) clusters expand into the inactive (laminar) phase with a well-defined velocity whose scaling with control parameter (Reynolds number or percolation probability) is consistent with experimental results. Our results provide strong evidence in favor of a conjecture of Pomeau. PMID- 22060448 TI - Geometrical interpretation of negative radiation forces of acoustical Bessel beams on spheres. AB - Various researchers have predicted situations where the acoustical or optical radiation force on a sphere centered on a Bessel beam is opposite the direction of beam propagation. We develop the analogy between acoustical and optical radiation forces of arbitrary-order helicoidal and ordinary Bessel beams to gain insight into negative radiation forces. The radiation force is expressed in terms of the asymmetry of the scattered field, the scattered power, the absorbed power, and the conic angle of the Bessel beam and is related to the partial-wave coefficients for the scattering. Negative forces only occur when the scattering into the backward hemisphere is suppressed relative to the scattering into the forward hemisphere. Absorbed power degrades negative radiation forces. PMID- 22060449 TI - Bright solitons from defocusing nonlinearities. AB - We report that defocusing cubic media with spatially inhomogeneous nonlinearity, whose strength increases rapidly enough toward the periphery, can support stable bright localized modes. Such nonlinearity landscapes give rise to a variety of stable solitons in all three dimensions, including one-dimensional fundamental and multihump states, two-dimensional vortex solitons with arbitrarily high topological charges, and fundamental solitons in three dimensions. Solitons maintain their coherence in the state of motion, oscillating in the nonlinear potential as robust quasiparticles and colliding elastically. In addition to numerically found soliton families, particular solutions are found in an exact analytical form, and accurate approximations are developed for the entire families, including moving solitons. PMID- 22060450 TI - Structural control of reaction-diffusion networks. AB - Recent studies revealed that reaction-diffusion (RD) dynamics can be significantly influenced by the structure of the underlying network. In this paper, a framework is established to study a closely related problem, i.e., to control the proportion of active particles in an RD process by adjusting the structure of the underlying diffusion network. Both distributed and centralized rewiring and reweighting control schemes are proposed for unweighted and weighted networks, respectively. Simulations show that the proportion of active particles can indeed be controlled to a certain extent even when the distributed control mechanism is totally random, while quite high precision can be achieved by centralized control schemes. More interestingly, it is found that the reactants in heterogeneous networks have wider controllable ranges than those in homogeneous networks with similar numbers of nodes and links, if only the weights of links are changed with a fixed bound. Therefore, it is believed that heterogeneous networks fit the changeable environment better, which provides another explanation for some common observations on many heterogeneous real-world networks. PMID- 22060451 TI - Reinforced communication and social navigation: remember your friends and remember yourself. AB - In social systems, people communicate with each other and form groups based on their interests. The pattern of interactions, the network, and the ideas that flow on the network naturally evolve together. Researchers use simple models to capture the feedback between changing network patterns and ideas on the network, but little is understood about the role of past events in the feedback process. Here, we introduce a simple agent-based model to study the coupling between peoples' ideas and social networks, and better understand the role of history in dynamic social networks. We measure how information about ideas can be recovered from information about network structure and, the other way around, how information about network structure can be recovered from information about ideas. We find that it is, in general, easier to recover ideas from the network structure than vice versa. PMID- 22060452 TI - Efficient and principled method for detecting communities in networks. AB - A fundamental problem in the analysis of network data is the detection of network communities, groups of densely interconnected nodes, which may be overlapping or disjoint. Here we describe a method for finding overlapping communities based on a principled statistical approach using generative network models. We show how the method can be implemented using a fast, closed-form expectation-maximization algorithm that allows us to analyze networks of millions of nodes in reasonable running times. We test the method both on real-world networks and on synthetic benchmarks and find that it gives results competitive with previous methods. We also show that the same approach can be used to extract nonoverlapping community divisions via a relaxation method, and demonstrate that the algorithm is competitively fast and accurate for the nonoverlapping problem. PMID- 22060453 TI - Average crack-front velocity during subcritical fracture propagation in a heterogeneous medium. AB - We study the average velocity of crack fronts during stable interfacial fracture experiments in a heterogeneous quasibrittle material under constant loading rates and during long relaxation tests. The transparency of the material (polymethylmethacrylate) allows continuous tracking of the front position and relation of its evolution to the energy release rate. Despite significant velocity fluctuations at local scales, we show that a model of independent thermally activated sites successfully reproduces the large-scale behavior of the crack front for several loading conditions. PMID- 22060454 TI - Nonperturbative heterogeneous mean-field approach to epidemic spreading in complex networks. AB - Since roughly a decade ago, network science has focused among others on the problem of how the spreading of diseases depends on structural patterns. Here, we contribute to further advance our understanding of epidemic spreading processes by proposing a nonperturbative formulation of the heterogeneous mean-field approach that has been commonly used in the physics literature to deal with this kind of spreading phenomena. The nonperturbative equations we propose have no assumption about the proximity of the system to the epidemic threshold, nor any linear approximation of the dynamics. In particular, we first develop a probabilistic description at the node level of the epidemic propagation for the so-called susceptible-infected-susceptible family of models, and after we derive the corresponding heterogeneous mean-field approach. We propose to use the full extension of the approach instead of pruning the expansion to first order, which leads to a nonperturbative formulation that can be solved by fixed-point iteration, and used with reliability far away from the epidemic threshold to assess the prevalence of the epidemics. Our results are in close agreement with Monte Carlo simulations, thus enhancing the predictive power of the classical heterogeneous mean-field approach, while providing a more effective framework in terms of computational time. PMID- 22060455 TI - Competing epidemics on complex networks. AB - Human diseases spread over networks of contacts between individuals and a substantial body of recent research has focused on the dynamics of the spreading process. Here we examine a model of two competing diseases spreading over the same network at the same time, where infection with either disease gives an individual subsequent immunity to both. Using a combination of analytic and numerical methods, we derive the phase diagram of the system and estimates of the expected final numbers of individuals infected with each disease. The system shows an unusual dynamical transition between dominance of one disease and dominance of the other as a function of their relative rates of growth. Close to this transition the final outcomes show strong dependence on stochastic fluctuations in the early stages of growth, dependence that decreases with increasing network size, but does so sufficiently slowly as still to be easily visible in systems with millions or billions of individuals. In most regions of the phase diagram we find that one disease eventually dominates while the other reaches only a vanishing fraction of the network, but the system also displays a significant coexistence regime in which both diseases reach epidemic proportions and infect an extensive fraction of the network. PMID- 22060456 TI - Pedestrian flow dynamics in a lattice gas model coupled with an evolutionary game. AB - This paper studies unidirectional pedestrian flow by using a lattice gas model with parallel update rules. Game theory is introduced to deal with conflicts that two or three pedestrians want to move into the same site. Pedestrians are either cooperators or defectors. The cooperators are gentle and the defectors are aggressive. Moreover, pedestrians could change their strategy. The fundamental diagram and the cooperator fraction at different system width W have been investigated in detail. It is found that a two-lane system exhibits a first-order phase transition while a multilane system does not. A microscopic mechanism behind the transition has been provided. Mean-field analysis is carried out to calculate the critical density of the transition as well as the probability of games at large value of W. The spatial distribution of pedestrians is investigated, which is found to be dependent (independent) on the initial cooperator fraction when W is small (large). Finally, the influence of the evolutionary game rule has been discussed. PMID- 22060457 TI - Dual modeling of political opinion networks. AB - We present the result of a dual modeling of opinion networks. The model complements the agent-based opinion models by attaching to the social agent (voters) network a political opinion (party) network having its own intrinsic mechanisms of evolution. These two subnetworks form a global network, which can be either isolated from, or dependent on, the external influence. Basically, the evolution of the agent network includes link adding and deleting, with the opinion changes influenced by social validation, the political climate, the attractivity of the parties, and the interaction between them. The opinion network is initially composed of numerous nodes representing opinions or parties that are located on a one dimensional axis according to their political positions. The mechanism of evolution includes union, splitting, change of position, and attractivity, taking into account the pairwise node interaction decaying with node distance in power law. The global evolution ends in a stable distribution of the social agents over a quasistable and fluctuating stationary number of remaining parties. Empirical study on the lifetime distribution of numerous parties and vote results is carried out to verify numerical results. PMID- 22060458 TI - Finding communities in linear time by developing the seeds. AB - We present an alternate method for finding the communities in a complex network. We introduce two concepts named the seed of the community and the absorption power of the seed in complex networks. First, we find the seeds and then develop them by considering their absorption power to achieve the communities. We compare the modularity and the computational complexity of this algorithm with some other existing methods, and we show that this algorithm is very fast and efficient in comparison with some recently fast algorithms. PMID- 22060459 TI - Epidemic spreading in networks with nonrandom long-range interactions. AB - An "infection," understood here in a very broad sense, can be propagated through the network of social contacts among individuals. These social contacts include both "close" contacts and "casual" encounters among individuals in transport, leisure, shopping, etc. Knowing the first through the study of the social networks is not a difficult task, but having a clear picture of the network of casual contacts is a very hard problem in a society of increasing mobility. Here we assume, on the basis of several pieces of empirical evidence, that the casual contacts between two individuals are a function of their social distance in the network of close contacts. Then, we assume that we know the network of close contacts and infer the casual encounters by means of nonrandom long-range (LR) interactions determined by the social proximity of the two individuals. This approach is then implemented in a susceptible-infected-susceptible (SIS) model accounting for the spread of infections in complex networks. A parameter called "conductance" controls the feasibility of those casual encounters. In a zero conductance network only contagion through close contacts is allowed. As the conductance increases the probability of having casual encounters also increases. We show here that as the conductance parameter increases, the rate of propagation increases dramatically and the infection is less likely to die out. This increment is particularly marked in networks with scale-free degree distributions, where infections easily become epidemics. Our model provides a general framework for studying epidemic spreading in networks with arbitrary topology with and without casual contacts accounted for by means of LR interactions. PMID- 22060460 TI - Elastic response of a grounded ice sheet coupled to a floating ice shelf. AB - An ice sheet that spreads into an ocean is forced to bend owing to its buoyancy and detaches from the bedrock to form a floating ice shelf. The location of the transition between the grounded sheet and the floating shelf, defined as the grounding line, behaves as a free boundary. We develop a model of an elastic grounded sheet resting on a deformable elastic bed and coupled to an elastic floating shelf. We find that the grounding-line position is determined by the geometry of the bed and the bending-buoyancy length scale of the system. These two contributions depend on the reaction modulus of the bed in opposite ways. We show that the structure of the floating shelf depends on the bending-buoyancy length scale only, allowing us to calculate the bending stiffness of the elastic sheet independently of the properties of the bed. Relations between the structure of the floating shelf and the grounding-line position are also developed. Our theoretical predictions agree with laboratory experiments made using thick elastic sheets and a dense salt solution. Our findings may provide new insights into the dynamics near grounding lines, as well as methods to infer the bending stiffness of ice sheets and the grounding-line position from satellite altimetery that can be applied to elastic sheets in general. PMID- 22060461 TI - Scaling and entropy in p-median facility location along a line. AB - The p-median problem is a common model for optimal facility location. The task is to place p facilities (e.g., warehouses or schools) in a heterogeneously populated space such that the average distance from a person's home to the nearest facility is minimized. Here we study the special case where the population lives along a line (e.g., a road or a river). If facilities are optimally placed, the length of the line segment served by a facility is inversely proportional to the square root of the population density. This scaling law is derived analytically and confirmed for concrete numerical examples of three US interstate highways and the Mississippi River. If facility locations are permitted to deviate from the optimum, the number of possible solutions increases dramatically. Using Monte Carlo simulations, we compute how scaling is affected by an increase in the average distance to the nearest facility. We find that the scaling exponents change and are most sensitive near the optimum facility distribution. PMID- 22060462 TI - Effects of dynamical grouping on cooperation in N-person evolutionary snowdrift game. AB - A population typically consists of agents that continually distribute themselves into different groups at different times. This dynamic grouping has recently been shown to be essential in explaining many features observed in human activities including social, economic, and military activities. We study the effects of dynamic grouping on the level of cooperation in a modified evolutionary N-person snowdrift game. Due to the formation of dynamical groups, the competition takes place in groups of different sizes at different times and players of different strategies are mixed by the grouping dynamics. It is found that the level of cooperation is greatly enhanced by the dynamic grouping of agents, when compared with a static population of the same size. As a parameter beta, which characterizes the relative importance of the reward and cost, increases, the fraction of cooperative players f(C) increases and it is possible to achieve a fully cooperative state. Analytically, we present a dynamical equation that incorporates the effects of the competing game and group size distribution. The distribution of cooperators in different groups is assumed to be a binomial distribution, which is confirmed by simulations. Results from the analytic equation are in good agreement with numerical results from simulations. We also present detailed simulation results of f(C) over the parameter space spanned by the probabilities of group coalescence nu(m) and group fragmentation nu(p) in the grouping dynamics. A high nu(m) and low nu(p) promotes cooperation, and a favorable reward characterized by a high beta would lead to a fully cooperative state. PMID- 22060463 TI - Computing equilibrium concentrations for large heterodimerization networks. AB - We consider a chemical reaction network governed by mass action kinetics and composed of N different species which can reversibly form heterodimers. A fast iterative algorithm is introduced to compute te equilibrium concentrations of such networks. We show that the convergence is guaranteed by the Banach fixed point theorem. As a practical example of relevance for a quantitative analysis of microarray data, we consider a reaction network formed by N~10(6) mutually hybridizing different mRNA sequences. We show that, despite the large number of species involved, the convergence to equilibrium is very rapid for most species. The origin of slow convergence for some specific subnetworks is discussed. This provides some insights for improving the performance of the algorithm. PMID- 22060464 TI - Voter model with non-Poissonian interevent intervals. AB - Recent analysis of social communications among humans has revealed that the interval between interactions for a pair of individuals and for an individual often follows a long-tail distribution. We investigate the effect of such a non Poissonian nature of human behavior on dynamics of opinion formation. We use a variant of the voter model and numerically compare the time to consensus of all the voters with different distributions of interevent intervals and different networks. Compared with the exponential distribution of interevent intervals (i.e., the standard voter model), the power-law distribution of interevent intervals slows down consensus on the ring. This is because of the memory effect; in the power-law case, the expected time until the next update event on a link is large if the link has not had an update event for a long time. On the complete graph, the consensus time in the power-law case is close to that in the exponential case. Regular graphs bridge these two results such that the slowing down of the consensus in the power-law case as compared to the exponential case is less pronounced as the degree increases. PMID- 22060465 TI - Scaling relations for watersheds. AB - We study the morphology of watersheds in two and three dimensional systems subjected to different degrees of spatial correlations. The response of these objects to small, local perturbations is also investigated with extensive numerical simulations. We find the fractal dimension of the watersheds to generally decrease with the Hurst exponent, which quantifies the degree of spatial correlations. Moreover, in two dimensions, our results match the range of fractal dimensions 1.10<=d(f)<=1.15 observed for natural landscapes. We report that the watershed is strongly affected by local perturbations. For perturbed two and three dimensional systems, we observe a power-law scaling behavior for the distribution of areas (volumes) enclosed by the original and the displaced watershed and for the distribution of distances between outlets. Finite-size effects are analyzed and the resulting scaling exponents are shown to depend significantly on the Hurst exponent. The intrinsic relation between watershed and invasion percolation, as well as relations between exponents conjectured in previous studies with two dimensional systems, are now confirmed by our results in three dimensions. PMID- 22060466 TI - Computationally efficient measure of topological redundancy of biological and social networks. AB - It is well known that biological and social interaction networks have a varying degree of redundancy, though a consensus of the precise cause of this is so far lacking. In this paper, we introduce a topological redundancy measure for labeled directed networks that is formal, computationally efficient, and applicable to a variety of directed networks such as cellular signaling, and metabolic and social interaction networks. We demonstrate the computational efficiency of our measure by computing its value and statistical significance on a number of biological and social networks with up to several thousands of nodes and edges. Our results suggest a number of interesting observations: (1) Social networks are more redundant that their biological counterparts, (2) transcriptional networks are less redundant than signaling networks, (3) the topological redundancy of the C. elegans metabolic network is largely due to its inclusion of currency metabolites, and (4) the redundancy of signaling networks is highly (negatively) correlated with the monotonicity of their dynamics. PMID- 22060467 TI - Multifractality of complex networks. AB - We demonstrate analytically and numerically the possibility that the fractal property of a scale-free network cannot be characterized by a unique fractal dimension and the network takes a multifractal structure. It is found that the mass exponents tau(q) for several deterministic, stochastic, and real-world fractal scale-free networks are nonlinear functions of q, which implies that structural measures of these networks obey the multifractal scaling. In addition, we give a general expression of tau(q) for some class of fractal scale-free networks by a mean-field approximation. The multifractal property of network structures is a consequence of large fluctuations of local node density in scale free networks. PMID- 22060468 TI - Locally self-organized quasicritical percolation in a multiple-disease model. AB - Diseases emerge, persist, and vanish in an ongoing battle for available hosts. Hosts, on the other hand, defend themselves by developing immunity that limits the ability of pathogens to reinfect them. We here explore a multidisease system with emphasis on mutual exclusion. We demonstrate that such a system develops toward a steady state, where the spread of individual diseases self-organizes to a state close to that of critical percolation, without any global control mechanism or separation of time scale. For a broad range of introduction rates of new diseases, the likelihood of transmitting diseases remains approximately constant. PMID- 22060469 TI - Skew-varicose instability in two-dimensional generalized Swift-Hohenberg equations. AB - We apply analytical and numerical methods to study the linear stability of stripe patterns in two generalizations of the two-dimensional Swift-Hohenberg equation that include coupling to a mean flow. A projection operator is included in our models to allow exact stripe solutions. In the generalized models, stripes become unstable to the skew-varicose, oscillatory skew-varicose, and cross-roll instabilities, in addition to the usual Eckhaus and zigzag instabilities. We analytically derive stability boundaries for the skew-varicose instability in various cases, including several asymptotic limits. We also use numerical techniques to determine eigenvalues and hence stability boundaries of other instabilities. We extend our analysis to both stress-free and no-slip boundary conditions and we note a crossover from the behavior characteristic of no-slip to that of stress-free boundaries as the coupling to the mean flow increases or as the Prandtl number decreases. Close to the critical value of the bifurcation parameter, the skew-varicose instability has the same curvature as the Eckhaus instability provided the coupling to the mean flow is greater than a critical value. The region of stable stripes is completely eliminated by the cross-roll instability for large coupling to the mean flow. PMID- 22060470 TI - Current reversals of coupled driven and damped particles evolving in a tilted potential landscape. AB - We explore the driven and damped dynamics of two coupled particles evolving in a symmetric and periodic substrate potential that is subjected to a static bias force. In addition, each particle is time-periodically driven with the same magnitude as, but out of phase to, its counterpart. It is shown that, for a certain parameter regime, the coupled particles can become self-organized and go against the direction of the bias force. This self-organization involves the particles becoming frequency locked with the driving force, and thus periodic motion ensues. We employ numerical arguments to show that running periodic states provide solutions of the system. Further, heuristic evidence is provided explaining how the two particles can travel against the bias force. In an effort to unearth coupling phenomena within the system, a detailed analysis of how the coupling strength affects the nonlinear dynamics is carried out. We show that within a range of coupling strengths the existence of periodic running solutions associated with negative mobility. To examine the robustness of our results we compare the deterministic system with the corresponding Langevin system. It is shown that, below a critical temperature, the qualitative behavior of the system remains the same. PMID- 22060471 TI - Deterministic fractals: extracting additional information from small-angle scattering data. AB - The small-angle scattering curves of deterministic mass fractals are studied and analyzed in momentum space. In the fractal region, the curve I(q)q(D) is found to be log-periodic with good accuracy, and the period is equal to the scaling factor of the fractal. Here, D and I(q) are the fractal dimension and the scattering intensity, respectively. The number of periods of this curve coincides with the number of fractal iterations. We show that the log-periodicity of I(q)q(D) in the momentum space is related to the log-periodicity of the quantity g(r)r(3-D) in the real space, where g(r) is the pair distribution function. The minima and maxima positions of the scattering intensity are estimated explicitly by relating them to the pair distance distribution in real space. It is shown that the minima and maxima are damped with increasing polydispersity of the fractal sets; however, they remain quite pronounced even at sufficiently large values of polydispersity. A generalized self-similar Vicsek fractal with controllable fractal dimension is introduced, and its scattering properties are studied to illustrate the above findings. In contrast with the usual methods, the present analysis allows us to obtain not only the fractal dimension and the edges of the fractal region, but also the fractal iteration number, the scaling factor, and the number of structural units from which the fractal is composed. PMID- 22060472 TI - Energy gain induced by boundary crisis. AB - We consider a nonlinear system and show the unexpected and surprising result that, even for high dissipation, the mean energy of a particle can attain higher values than when there is no dissipation in the system. We reconsider the time dependent annular billiard in the presence of inelastic collisions with the boundaries. For some magnitudes of dissipation, we observe the phenomenon of boundary crisis, which drives the particles to an asymptotic attractive fixed point located at a value of energy that is higher than the mean energy of the nondissipative case and so much higher than the mean energy just before the crisis. We should emphasize that the unexpected results presented here reveal the importance of a nonlinear dynamics analysis to explain the paradoxical strategy of introducing dissipation in the system in order to gain energy. PMID- 22060473 TI - Coalescence cascade of dissipative solitons in parametrically driven systems. AB - Parametrically driven spatially extended systems exhibit uniform oscillations which are modulationally unstable. The resulting periodic state evolves to the creation of a gas of dissipative solitons. Driven by the interaction of dissipative solitons, the multisoliton state undergoes a cascade of coalescence processes, where the average soliton separation distance obeys a temporal self similar law. Starting from the soliton pair interaction law, we have derived analytically and characterized the law of this multisoliton coarsening process. A comparison of numerical results obtained with different models such as the parametrically driven damped nonlinear Schrodinger equation, a vertically driven chain of pendula, and a parametrically forced magnetic wire, shows remarkable agreement. Both phenomena, the pair interaction law and the coarsening process, are also observed experimentally in a quasi-one-dimensional layer of Newtonian fluid which is oscillated vertically. PMID- 22060474 TI - Multivariate singular spectrum analysis and the road to phase synchronization. AB - We show that multivariate singular spectrum analysis (M-SSA) greatly helps study phase synchronization in a large system of coupled oscillators and in the presence of high observational noise levels. With no need for detailed knowledge of individual subsystems nor any a priori phase definition for each of them, we demonstrate that M-SSA can automatically identify multiple oscillatory modes and detect whether these modes are shared by clusters of phase- and frequency-locked oscillators. As an essential modification of M-SSA, here we introduce variance maximization (varimax) rotation of the M-SSA eigenvectors to optimally identify synchronized-oscillator clustering. PMID- 22060475 TI - Chaos computing in terms of periodic orbits. AB - The complex dynamics of chaotic systems can perform computations. The parameters and/or the initial conditions of a dynamical system are the data inputs and the resulting system state is the output of the computation. By controlling how inputs are mapped to outputs, a specific function can be performed. Previously no clear connection has been drawn between the structure of the dynamics and the computation. In this paper we demonstrate how chaos computation can be explained, modeled, and even predicted in terms of the dynamics of the underlying chaotic system, specifically the periodic orbit structure of the system. Knowing the dynamical equations of the system, we compute the system's periodic orbits as well as its stability in terms of its eigenvalues, thereby demonstrating how, how well, and what the chaotic system can compute. PMID- 22060476 TI - Cluster synchrony in systems of coupled phase oscillators with higher-order coupling. AB - We study the phenomenon of cluster synchrony that occurs in ensembles of coupled phase oscillators when higher-order modes dominate the coupling between oscillators. For the first time, we develop a complete analytic description of the dynamics in the limit of a large number of oscillators and use it to quantify the degree of cluster synchrony, cluster asymmetry, and switching. We use a variation of the recent dimensionality-reduction technique of Ott and Antonsen [Chaos 18, 037113 (2008)] and find an analytic description of the degree of cluster synchrony valid on a globally attracting manifold. Shaped by this manifold, there is an infinite family of steady-state distributions of oscillators, resulting in a high degree of multistability in the cluster asymmetry. We also show how through external forcing the degree of asymmetry can be controlled, and suggest that systems displaying cluster synchrony can be used to encode and store data. PMID- 22060477 TI - Solitary and coupled semiconductor ring lasers as optical spiking neurons. AB - We theoretically investigate the possibility of generating pulses in an excitable (asymmetric) semiconductor ring laser (SRL) using optical trigger pulses. We show that the phase difference between the injected field and the electric field inside the SRL determines the direction of the perturbation in phase space. Due to the folded shape of the excitability threshold, this has an important influence on the ability to cross it. A mechanism for exciting multiple consecutive pulses using a single trigger pulse (i.e., multipulse excitability) is revealed. We furthermore investigate the possibility of using asymmetric SRLs in a coupled configuration, which is a first step toward an all-optical neural network using SRLs as building blocks. PMID- 22060478 TI - General coupled-nonlinear-oscillator model for event-related (de)synchronization. AB - Changes in the level of synchronization and desynchronization in coupled oscillator systems due to an external stimulus are called event-related synchronization or desynchronization (ERS or ERD). Such changes occur in real life systems where the collective activity of the entities of a coupled system is affected by some external influence. In order to understand the role played by the external influence in the occurrence of ERD and ERS, we study a system of coupled nonlinear oscillators in the presence of an external stimulus signal. We find that the phenomena of ERS and ERD are generic and occur in all types of coupled oscillator systems. We also find that the same external stimulus signal can cause ERS and ERD depending upon the strength of the signal. We identify the stability of the ERS and ERD states and also find analytical and numerical boundaries between the different synchronization regimes involved in the occurrence of ERD and ERS. PMID- 22060479 TI - Species mobility induces synchronization in chaotic population dynamics. AB - A prototype population dynamics model with cyclic domination of four species and empty sites is proposed for studying transition to synchronization. At the mean field level the dynamics shows quasiperiodicity and chaos depending on the parameter values. The realization of the model on a square lattice shows that spatial restrictions and intrinsic stochasticity change the whole picture. The mean-field dynamics qualitatively remains only under global reactions, while local reactions drive the lattice to poisoning, where only some of the species survive. Nontrivial oscillatory steady states are developed if long-distance exchange is introduced due to gradual mixing with a certain probability. The mixing probability is shown to control the transition to synchronization which emerges abruptly following a phase slip scenario. Near the transition a typical intermittency crisis takes place, with phase slips becoming more infrequent as the transition is approached. PMID- 22060480 TI - Perturbation approach to multifractal dimensions for certain critical random matrix ensembles. AB - Fractal dimensions of eigenfunctions for various critical random matrix ensembles are investigated in perturbation series in the regimes of strong and weak multifractality. In both regimes, we obtain expressions similar to those of the critical banded random matrix ensemble extensively discussed in the literature. For certain ensembles, the leading-order term for weak multifractality can be calculated within standard perturbation theory. For other models, such a direct approach requires modifications, which are briefly discussed. Our analytical formulas are in good agreement with numerical calculations. PMID- 22060481 TI - From one- to two-dimensional solitons in the Ginzburg-Landau model of lasers with frequency-selective feedback. AB - We use the cubic complex Ginzburg-Landau equation linearly coupled to a dissipative linear equation as a model for lasers with an external frequency selective feedback. This system may also serve as a general pattern-formation model in media driven by an intrinsic gain and selective feedback. While, strictly speaking, the approximation of the laser nonlinearity by a cubic term is only valid for small field intensities, it qualitatively reproduces results for dissipative solitons obtained in models with a more complex nonlinearity in the whole parameter region where the solitons exist. The analysis is focused on two dimensional stripe-shaped and vortex solitons. An analytical expression for the stripe solitons is obtained from the known one-dimensional soliton solution, and its relation with vortex solitons is highlighted. The radius of the vortices increases linearly with their topological charge m, therefore the stripe-shaped soliton may be interpreted as the vortex with m=infinity, and, conversely, vortex solitons can be realized as unstable stripes bent into stable rings. The results for the vortices are applicable for a broad class of physical systems. PMID- 22060482 TI - Delay independence of mutual-information rate of two symbolic sequences. AB - Introduced by Shannon as a "rate of actual transmission," mutual information rate (MIR) is an extension of mutual information to a pair of dynamical processes. We show a delay-independence theorem, according to which MIR is not sensitive to a time shift between the two processes. Numerical studies of several benchmark situations confirm that this theoretical asymptotic property remains valid for realistic finite sequences. Estimations based on block entropies and a causal state machine algorithm perform better than an estimation based on a Lempel-Ziv compression algorithm provided that block length and maximum history length, respectively, can be chosen larger than the delay. MIR is thus a relevant index for measuring nonlinear correlations between two experimental or simulated sequences when the transmission delay (in input-output devices) or dephasing (in coupled systems) is variable or unknown. PMID- 22060483 TI - Prognosis of qualitative system behavior by noisy, nonstationary, chaotic time series. AB - An approach to prognosis of qualitative behavior of an unknown dynamical system (DS) from weakly nonstationary chaotic time series (TS) containing significant measurement noise is proposed. The approach is based on construction of a global time-dependent parametrized model of discrete evolution operator (EO) capable of reproducing nonstationary dynamics of a reconstructed DS. A universal model in the form of artificial neural network (ANN) with certain prior limitations is used for the approximation of the EO in the reconstructed phase space. Probabilistic prognosis of the system behavior is performed using Monte Carlo Markov chain (MCMC) analysis of the posterior Bayesian distribution of the model parameters. The classification of qualitatively different regimes is supposed to be dictated by the application, i.e., it is assumed that some classifier function is predefined that maps a point of a model parameter space to a finite set of different behavior types. The ability of the approach to provide prognosis for times comparable to the observation time interval is demonstrated. Some restrictions as well as possible advances of the proposed approach are discussed. PMID- 22060484 TI - Amplitude equations for reaction-diffusion systems with cross diffusion. AB - Using Taylor series expansion, multiscaling, and further expansion in powers of a small parameter, we develop general amplitude equations for two-variable reaction diffusion systems with cross-diffusion terms in the cases of Hopf and Turing instabilities. We apply this analysis to the Oregonator and Brusselator models and find that inhibitor cross diffusion induced by the activator and activator cross diffusion induced by the inhibitor have opposite effects in the two models as a result of the different structure of their community matrices. Our analysis facilitates finding regions of supercritical and subcritical bifurcations, as well as wave and antiwave domains and domains of turbulent waves in the case of Hopf instability. PMID- 22060485 TI - Relaxation of an unstable state in parametrically excited cold atoms. AB - We investigate the scaling behavior of the relaxation process for an unstable state near a subcritical Hopf bifurcation point. When the parametric modulation is applied to a magneto-optical trap, the atomic cloud becomes unstable and decays to the dynamic bistable states. Near the subcritical Hopf bifurcation point, we experimentally show that the relaxation process exhibits the scaling behavior; the relaxation time shows a scaling exponent of -1.002 (+/-0.024). We also present the passage time distribution for the statistical interpretation of the escape process associated with the relaxation of the unstable state. We compare the experimental results to the numerical and analytic results, demonstrating the good agreement between them. PMID- 22060486 TI - Electro-osmotic flow through a two-dimensional screen-pump filter. AB - The electro-osmotic flow driven by a screen pump, composed of a line array of evenly spaced identical rectangular solid blocks, is investigated under the Debye Huckel approximation. The geometry of the screen pump is determined by the spacing and aspect ratio of the solid blocks. A constant surface zeta potential is assumed on the block surface. The method of eigenfunction series expansion is applied to solve analytically for the applied electric field, electric charge potential in the fluid, and flow field. Because of the low Reynolds number, Stokes equations are applied for the flow. The analytic result is first confirmed by comparing with the exact solution of the electro-osmotic flow in an infinite channel. Then different geometries of the screen pump and the effect of the electrokinetic width are computed for their influence on the flow rate. Recirculating eddies and reversing flow are found even though the applied electric driving field is unidirectional. PMID- 22060487 TI - Sheathless hydrodynamic positioning of buoyant drops and bubbles inside microchannels. AB - Particles, bubbles, and drops carried by a fluid in a confined environment such as a pipe can be subjected to hydrodynamic lift forces, i.e., forces that are perpendicular to the direction of the flow. We investigated the positioning effect of lift forces acting on buoyant drops and bubbles suspended in a carrier fluid and flowing in a horizontal microchannel. We report experiments on drops of water in fluorocarbon liquid, and on bubbles of nitrogen in hydrocarbon liquid and silicone oil, inside microchannels with widths on the order of 0.1-1 mm. Despite their buoyancy, drops and bubbles could travel without contacting with the walls of channels; the most important parameters for reaching this flow regime in our experiments were the viscosity and the velocity of the carrier fluid, and the sizes of drops and bubbles. The dependencies of the transverse position of drops and bubbles on these parameters were investigated. At steady state, the trajectories of drops and bubbles approached the center of the channel for drops and bubbles almost as large as the channel, carried by rapidly flowing viscous liquids; among our experiments, these flow conditions were characterized by larger capillary numbers and smaller Reynolds numbers. Analytical models of lift forces developed for the flow of drops much smaller than the width of the channel failed to predict their transverse position, while computational fluid dynamic simulations of the experiments agreed better with the experimental measurements. The degrees of success of these predictions indicate the importance of confinement on generating strong hydrodynamic lift forces. We conclude that, inside microfluidic channels, it is possible to support and position buoyant drops and bubbles simply by flowing a single-stream (i.e., "sheathless") carrier liquid that has appropriate velocity and hydrodynamic properties. PMID- 22060488 TI - Effect of added salt on preformed surface nanobubbles: a scaling estimate. AB - In this paper we propose a scaling argument to quantify the role of added electrolyte salt in affecting the stability and the morphology of preformed surface nanobubbles on hydrophobic substrates like the water-OTS-silicon or the water-HOPG interfaces. The added salt controls the electric double layer formation as well as affects the zeta (zeta) potential at the air-water and solid water interfaces. The resulting electrostatic wetting tension acts in conjunction with the air-water surface tension (analogous to electrowetting scenarios), thereby affecting the nanobubble morphologies. Weak zeta potential of the water HOPG interface or the water-OTS-silicon interface at acidic pH ensures that the added salt will have imperceptible effect on the corresponding preformed surface nanobubbles, validating the experimental observations. However, at alkaline buffer pH for the OTS-silicon substrate, under certain system conditions, salt induced zeta potential can be substantially high so that the properties of preformed surface nanobubbles will be affected. This paper will thus readdress the long-held universal notion that added salt, no matter in what concentration, will not influence the properties of preformed surface nanobubbles. PMID- 22060489 TI - Paradoxes of magnetorotational instability and their geometrical resolution. AB - Magnetorotational instability (MRI) triggers turbulence and enables outward transport of angular momentum in hydrodynamically stable accretion discs. By using the WKB approximation and methods of singular function theory, we resolve two different paradoxes of MRI that appear in the limits of infinite and vanishing magnetic Prandtl number. For the latter case, we derive a strict limit of the critical Rossby number. This limit of Ro(c)=-0.802, which appears for a finite Lundquist number of S=0.618, extends the formerly known inductionless Liu limit of Ro(c)=-0.828 valid at S=0. PMID- 22060490 TI - Droplet spreading on chemically heterogeneous substrates. AB - Consider the spreading dynamics of a two-dimensional droplet over chemically heterogeneous substrates. Assuming small slopes and strong surface tension effects, a long-wave expansion of the Stokes equations yields a single evolution equation for the droplet thickness. The contact line singularity is removed by assuming slip at the liquid-solid interface. The chemical nature of the substrate is incorporated by local variations in the microscopic contact angle, which appear as boundary conditions in the governing equation. By asymptotically matching the flow in the bulk of the droplet with the flow in the vicinity of the contact lines, we obtain a set of coupled ordinary differential equations for the locations of the two droplet fronts. We verify the validity of our matching procedure by comparing the solutions of the ordinary differential equations with solutions of the full governing equation. The droplet dynamics is examined in detail via a phase-plane analysis. A number of interesting features that are not present in chemically homogeneous substrates are found, such as the existence of multiple equilibria, the pinning of the droplet fronts at localized chemical features, and the possibility for the droplet fronts to exhibit a stick-slip behavior. PMID- 22060491 TI - Scalar fluctuations from a point source in a turbulent boundary layer. AB - The downstream development of the concentration probability distribution along the mean-plume centerline of a dispersing plume in the wake of a ground-level continuous point source in a neutrally stratified wall-shear layer is studied. It is shown that the concentration distribution is well described by a family of one parameter gamma distributions, as first suggested by Villermaux and Duplat [Phys. Rev. Lett. 91, 184501 (2003)] in the context of confined mixing. A prediction of the downstream evolution of the parameter k (which specifies the gamma distribution) is obtained. This prediction includes explicitly the effects of mean shear on the mean-square concentration. PMID- 22060492 TI - Permeability of isotropic and anisotropic fracture networks, from the percolation threshold to very large densities. AB - The asymptotic behaviors of the permeability of isotropic fracture networks at small and large densities are characterized, and a general heuristic formula is obtained which complies with the limiting behaviors and accurately predicts the permeability of these networks over the whole density range. Theses developments are based on extensive numerical calculations and on theoretical arguments inspired by the examination of the flow distribution in the fractures at large densities. Then, the results are extended to anisotropic networks with a Fisher distribution of the fracture orientations, to polydisperse networks, and to fractured porous media. Finally, guidelines are provided for the practical evaluation of the required parameters from typical field data. A summary of the results is given in Table III. PMID- 22060493 TI - Transient electrohydrodynamics of a liquid drop. AB - The transient behavior of a leaky dielectric liquid drop under a uniform electric field of small strength is investigated. It is shown that for small distortion from a spherical shape, the drop deforms to an ellipsoid, and the deformation time history is represented by D=D(infinity)[1-exp(-t/tau)], where D(infinity) is the steady-state deformation and tau=(aMU(o)/gamma)(19MU+16)(2MU+3)/(40MU+40)is the characteristic time, a, gamma, MU(o) and MU being the drop radius, the surface tension, the viscosity of ambient fluid, and ratio of the drop viscosity to that of the ambient fluid, respectively. The contributions of the net normal and tangential electrical stresses in the degree of deformation and fluid flow strength are also determined. PMID- 22060494 TI - Two-valued breakup length of a water jet issuing from a finite-length nozzle under normal gravity. AB - Laboratory experiments are conducted in which water is issued vertically downward from a finite-length nozzle at a constant speed using a piston. The results of these experiments indicate that the breakup length of the liquid jet is two valued at Weber numbers greater than unity but less than a certain value, which depends on the nozzle length-to-radius ratio and the Bond number. In addition to a long breakup length, which is consistent with the conventional observation, another shorter breakup length is realized at the same jet issue speed. Each experimental run for a specific jet issue speed begins from the start of liquid issue so that each run is independent of the other runs. Transition between the two breakup lengths seldom occurs in each run. Which of the two breakup lengths occurs is determined at the start of liquid issue, when the capillary wave produced by the liquid jet tip contraction easily reaches the nozzle exit. Unlike the conventional belief, which is based on the Plateau-Rayleigh instability theory, this experimental evidence demonstrates that liquid jet disintegration occurs in a deterministic manner. The previously proposed self-destabilizing mechanism of a liquid jet in microgravity, in which the origin of the unstable wave responsible for the breakups is attributed to the formation of an upstream propagating capillary wave at every breakup, is extended to explore the physics underlying the observed liquid jet disintegration behaviors. PMID- 22060495 TI - Inverse-Leidenfrost phenomenon on nanofiber mats on hot surfaces. AB - The Leidenfrost effect is a technically and industrially important phenomenon that severely restricts heat removal from high-heat-flux surfaces. A simple remedy to the Leidenfrost effect is provided by polymer nanofiber mats created and deposited by electrospinning on stainless steel surfaces. The influence of nanofiber mats on hydrodynamics and cooling efficiency of single drop impact onto hot surfaces has been investigated experimentally. The evolution of the drops has been recorded by a high-speed complimentary metal-oxide semiconductor camera, whereas the cooling temperature was measured by a thermocouple. A remarkable phenomenon was discovered: a mat of polymer nanofibers electrospun onto a heater surface can completely suppress the Leidenfrost effect, thereby increasing the rate of heat removal from the surface to the liquid drops significantly. The "inverse-Leidenfrost" effect is described qualitatively and quantitatively, providing clear physical reasons for the observed behavior. PMID- 22060496 TI - Nanoflow hydrodynamics. AB - We show by nonequilibrium molecular dynamics simulations that the Navier-Stokes equation does not correctly describe water flow in a nanoscale geometry. It is argued that this failure reflects the fact that the coupling between the intrinsic rotational and translational degrees of freedom becomes important for nanoflows. The coupling is correctly accounted for by the extended Navier-Stokes equations that include the intrinsic angular momentum as an independent hydrodynamic degree of freedom. PMID- 22060497 TI - Effect of vapor bubbles on velocity fluctuations and dissipation rates in bubbly Rayleigh-Benard convection. AB - Numerical results for kinetic and thermal energy dissipation rates in bubbly Rayleigh-Benard convection are reported. Bubbles have a twofold effect on the flow: on the one hand, they absorb or release heat to the surrounding liquid phase, thus tending to decrease the temperature differences responsible for the convective motion; but on the other hand, the absorbed heat causes the bubbles to grow, thus increasing their buoyancy and enhancing turbulence (or, more properly, pseudoturbulence) by generating velocity fluctuations. This enhancement depends on the ratio of the sensible heat to the latent heat of the phase change, given by the Jakob number, which determines the dynamics of the bubble growth. PMID- 22060498 TI - Moving walls accelerate mixing. AB - Mixing in viscous fluids is challenging, but chaotic advection in principle allows efficient mixing. In the best possible scenario, the decay rate of the concentration profile of a passive scalar should be exponential in time. In practice, several authors have found that the no-slip boundary condition at the walls of a vessel can slow down mixing considerably, turning an exponential decay into a power law. This slowdown affects the whole mixing region, and not just the vicinity of the wall. The reason is that when the chaotic mixing region extends to the wall, a separatrix connects to it. The approach to the wall along that separatrix is polynomial in time and dominates the long-time decay. However, if the walls are moved or rotated, closed orbits appear, separated from the central mixing region by a hyperbolic fixed point with a homoclinic orbit. The long-time approach to the fixed point is exponential, so an overall exponential decay is recovered, albeit with a thin unmixed region near the wall. PMID- 22060499 TI - Why the water bridge does not collapse. AB - In 2007 an interesting phenomenon was discovered [J. Phys. D 40, 6112 (2007)]: a horizontal thread of water, the so-called water bridge, hangs in a horizontal electrostatic field. A different explanation of the water bridge stability is proposed herein: the force supporting it is the surface tension of water, while the role of the electric field is to not allow the water bridge to reduce its surface energy by breaking into separate drops. It is proven that electrostatic field is not the origin of the tension holding the bridge. PMID- 22060500 TI - Heisenberg approximation in passive scalar turbulence. AB - We use Heisenberg's approximation to derive analytic expressions for eddy viscosity and eddy diffusivity from the transfer integrals of energy and mean square scalar arising from the Navier-Stokes and passive scalar dynamics. In the same scheme, we evaluate the flux integrals for the transports of energy and mean square scalar. These procedures allow for the evaluation of relevant amplitude ratios, from which we calculate the universal numbers, namely, Batchelor constant B, Kolmogorov constant C, and turbulent Prandtl number sigma, under two different schemes (with and without epsilon expansion). Our results are comparable with existing theoretical, numerical, and experimental values. As a byproduct, we obtain a relation between C, B, and sigma, namely, B=sigma C. To compare our results with the experimental values, we calculate Batchelor constant in one dimension (B'). Within the same framework, we also see that with increasing values of space dimension d, the Prandtl number sigma increases and approaches unity, while the Kolmogorov constant C and Batchelor constant B approach very close to each other. For large space dimensions, we find the asymptotic B=B(0)d(1/3), and evaluate B(0). PMID- 22060501 TI - Universality of scaling and multiscaling in turbulent symmetric binary fluids. AB - We elucidate the universal scaling and multiscaling properties of the nonequilibrium steady states in a driven symmetric binary fluid (SBF) mixture in its homogeneous miscible phase in three dimensions. We show, via direct numerical simulations (DNSs) that structure functions of the velocity and the concentration gradient exhibit multiscaling in three dimensions (3D) and extended self similarity. We also find that, in contrast to the well-known passive scalar turbulence problem, structure functions of the concentration show simple scaling. We propose a shell model for SBF turbulence that preserves all the invariances in the ideal limit of the SBF equations and reduces to a well-known shell model for fluid turbulence in the zero concentration field limit. We show that the shell model has the same scaling properties as the three-dimensional SBF equations. Our combined results from our DNSs of the SBF equations and shell-model studies consistently bring out the multiscaling of the velocity and concentration gradient fields and simple scaling of the concentration field. PMID- 22060502 TI - Generation and manipulation of monodispersed ferrofluid emulsions: the effect of a uniform magnetic field in flow-focusing and T-junction configurations. AB - This paper demonstrates the use of magnetically controlled microfluidic devices to produce monodispersed ferrofluid emulsions. By applying a uniform magnetic field on flow-focusing and T-junction configurations, the size of the ferrofluid emulsions can be actively controlled. The influences of the flow rates, the orientation, and the polarity of the magnetic field on the size of ferrofluid emulsions produced in both flow-focusing and T-junction configurations are compared and discussed. PMID- 22060503 TI - Linear and nonlinear evolution and diffusion layer selection in electrokinetic instability. AB - In the present work, four nontrivial stages of electrokinetic instability are identified by direct numerical simulation (DNS) of the full Nernst-Planck-Poisson Stokes system: (i) a stage of the influence of the initial conditions (milliseconds); (ii) one-dimensional (1D) self-similar evolution (milliseconds seconds); (iii) a primary instability of the self-similar solution (seconds); (iv) a nonlinear stage with secondary instabilities. The self-similar character of evolution at moderately large times is confirmed. Rubinstein and Zaltzman instability and noise-driven nonlinear evolution toward overlimiting regimes in ion-exchange membranes are numerically simulated and compared with theoretical and experimental predictions. The primary instability which happens during this stage is found to arrest a self-similar growth of the diffusion layer. It also specifies its characteristic length as was first experimentally predicted by Yossifon and Chang [G. Yossifon and H.-C. Chang, Phys. Rev. Lett. 101, 254501 (2008)]. A novel principle for the characteristic wave-number selection from the broadband initial noise is established. PMID- 22060504 TI - Hydraulic tortuosity in arbitrary porous media flow. AB - Tortuosity (T) is a parameter describing an average elongation of fluid streamlines in a porous medium as compared to free flow. In this paper several methods of calculating this quantity from lengths of individual streamlines are compared and their weak and strong features are discussed. An alternative method is proposed, which enables one to calculate T directly from the fluid velocity field, without the need of determining streamlines, which greatly simplifies determination of tortuosity in complex geometries, including those found in experiments or three-dimensional computer models. Based on numerical results obtained with this method, (a) a relation between the hydraulic tortuosity of an isotropic fibrous medium and the porosity is proposed, (b) a relation between the divergence rate of T with the system size at percolation porosity and the scaling of the most probable traveling length at bond percolation is found, and (c) a range of porosities for which the shape factor is constant is identified. PMID- 22060505 TI - Viscosity-ratio-based scaling for the rise velocity of a Taylor drop in a vertical tube. AB - Simulations of a silicon oil Taylor drop rising in a tube filled with a glycerol water mixture are performed to investigate the viscosity ratio effects on the rise velocity of the Taylor drop. By varying the viscosity ratio lambda between the drop and the suspending liquid from O(0.1) to O(10), a simple relationship of the nondimensional terminal velocity, the Froude number (Fr), is revealed as Fr ? lambda(-0.27). This scaling is further confirmed by recently published experimental data [Hayashi, Kurimoto, and Tomiyama, Int. J. Multiphase Flow 37, 241 (2011)]. The simulated drop shapes also compare well with the experiments. Increasing the viscosity ratio elongates the drop and tends to make the tail bulge out. The correlation applies to small Reynolds numbers and finite viscosity ratios. PMID- 22060506 TI - Periodic magnetorotational dynamo action as a prototype of nonlinear magnetic field generation in shear flows. AB - The nature of dynamo action in shear flows prone to magnetohydrodynamc instabilities is investigated using the magnetorotational dynamo in Keplerian shear flow as a prototype problem. Using direct numerical simulations and Newton's method, we compute an exact time-periodic magnetorotational dynamo solution to three-dimensional dissipative incompressible magnetohydrodynamic equations with rotation and shear. We discuss the physical mechanism behind the cycle and show that it results from a combination of linear and nonlinear interactions between a large-scale axisymmetric toroidal magnetic field and nonaxisymmetric perturbations amplified by the magnetorotational instability. We demonstrate that this large-scale dynamo mechanism is overall intrinsically nonlinear and not reducible to the standard mean-field dynamo formalism. Our results therefore provide clear evidence for a generic nonlinear generation mechanism of time-dependent coherent large-scale magnetic fields in shear flows and call for new theoretical dynamo models. These findings may offer important clues to understanding the transitional and statistical properties of subcritical magnetorotational turbulence. PMID- 22060507 TI - Nonlinear propagation of light in Dirac matter. AB - The nonlinear interaction between intense laser light and a quantum plasma is modeled by a collective Dirac equation coupled with the Maxwell equations. The model is used to study the nonlinear propagation of relativistically intense laser light in a quantum plasma including the electron spin-1/2 effect. The relativistic effects due to the high-intensity laser light lead, in general, to a downshift of the laser frequency, similar to a classical plasma where the relativistic mass increase leads to self-induced transparency of laser light and other associated effects. The electron spin-1/2 effects lead to a frequency upshift or downshift of the electromagnetic (EM) wave, depending on the spin state of the plasma and the polarization of the EM wave. For laboratory solid density plasmas, the spin-1/2 effects on the propagation of light are small, but they may be significant in superdense plasma in the core of white dwarf stars. We also discuss extensions of the model to include kinetic effects of a distribution of the electrons on the nonlinear propagation of EM waves in a quantum plasma. PMID- 22060508 TI - Rarefaction shock in plasma with a bi-Maxwellian electron distribution function. AB - The one-dimensional collisionless expansion into a vacuum of a plasma with a bi Maxwellian electron distribution function and a single ion species is studied both theoretically and numerically. A shock wave occurs when the ratio of the temperatures between the hot and the cold electrons is larger than 5+?24 [B. Bezzerides, D. W. Forslund, and E. L. Lindman, Phys. Fluids 21, 2179 (1978)]. The theoretical model presented here gives a coherent and complete description of the rarefaction shock and its effects on the ion acceleration process. Analytical expressions of the characteristics of the shock are given. The analytical findings are compared to the results of a hybrid code describing the plasma expansion, and an excellent agreement is obtained. PMID- 22060509 TI - Two-dimensional s-polarized solitary waves in relativistic plasmas. I. The fluid plasma model. AB - The properties of two-dimensional linearly s-polarized solitary waves are investigated by fluid-Maxwell equations and particle-in-cell (PIC) simulations. These self-trapped electromagnetic waves appear during laser-plasma interactions, and they have a dominant electric field component E(z), normal to the plane of the wave, that oscillates at a frequency below the electron plasma frequency omega(pe). A set of equations that describe the waves are derived from the plasma fluid model in the case of cold or warm plasma and then solved numerically. The main features, including the maximum value of the vector potential amplitude, the total energy, the width, and the cavitation radius are presented as a function of the frequency. The amplitude of the vector potential increases monotonically as the frequency of the wave decreases, whereas the width reaches a minimum value at a frequency of the order of 0.82 omega(pe). The results are compared with a set of PIC simulations where the solitary waves are excited by a high-intensity laser pulse. PMID- 22060510 TI - Two-dimensional s-polarized solitary waves in plasmas. II. Stability, collisions, electromagnetic bursts, and post-soliton evolution. AB - The dynamics of two-dimensional s-polarized solitary waves is investigated with the aid of particle-in-cell (PIC) simulations. Instead of the usual excitation of the waves with a laser pulse, the PIC code was directly initialized with the numerical solutions from the fluid plasma model. This technique allows the analysis of different scenarios including the theoretical problems of the solitary wave stability and their collision as well as features already measured during laser-plasma experiments such as the emission of electromagnetic bursts when the waves reach the plasma-vacuum interface, or their expansion on the ion time scale, usually named post-soliton evolution. Waves with a single density depression are stable whereas multihump solutions decay to several waves. Contrary to solitons, two waves always interact through a force that depends on their relative phases, their amplitudes, and the distance between them. On the other hand, the radiation pattern at the plasma-vacuum interface was characterized, and the evolution of the diameter of different waves was computed and compared with the "snow plow" model. PMID- 22060511 TI - Effects of laser-plasma interactions on terahertz radiation from solid targets irradiated by ultrashort intense laser pulses. AB - Interactions of 100-fs laser pulses with solid targets at intensities of 10(18) W/cm(2) and resultant terahertz (THz) radiation are studied under different laser contrast ratio conditions. THz emission is measured in the specular reflection direction, which appears to decrease as the laser contrast ratio varies from 10( 8) to 10(-6). Correspondingly, the frequency spectra of the reflected light are observed changing from second harmonic dominant, three-halves harmonic dominant, to vanishing of both harmonics. Two-dimensional particle-in-cell simulation also suggests that this observation is correlated with the plasma density scale length change. The results demonstrate that the THz emission is closely related to the laser-plasma interaction processes. The emission is strong when resonance absorption is a key feature of the interaction, and becomes much weaker when parametric instabilities dominate. PMID- 22060512 TI - Spatially resolved dynamic structure factor of finite systems from molecular dynamics simulations. AB - The dynamical response of metallic clusters up to 10(3) atoms is investigated using the restricted molecular dynamics simulations scheme. Exemplarily, a sodium like material is considered. Correlation functions are evaluated to investigate the spatial structure of collective electron excitations and the optical response of laser-excited clusters. In particular, the spectrum of bilocal correlation functions shows resonances representing different modes of collective excitations inside the nano plasma. The spatial structure, the resonance energy, and the width of the eigenmodes have been investigated for various values of electron density, temperature, cluster size, and ionization degree. Comparison with bulk properties is performed and the dispersion relation of collective excitations is discussed. PMID- 22060513 TI - Opacity of iron, nickel, and copper plasmas in the x-ray wavelength range: theoretical interpretation of 2p-3d absorption spectra. AB - This paper deals with theoretical studies on the 2p-3d absorption in iron, nickel, and copper plasmas related to LULI2000 (Laboratoire pour l'Utilisation des Lasers Intenses, 2000J facility) measurements in which target temperatures were of the order of 20 eV and plasma densities were in the range 0.004-0.01 g/cm(3). The radiatively heated targets were close to local thermodynamic equilibrium (LTE). The structure of 2p-3d transitions has been studied with the help of the statistical superconfiguration opacity code SCO and with the fine structure atomic physics codes HULLAC and FAC. A new mixed version of the sco code allowing one to treat part of the configurations by detailed calculation based on the Cowan's code RCG has been also used in these comparisons. Special attention was paid to comparisons between theory and experiment concerning the term features which cannot be reproduced by SCO. The differences in the spin orbit splitting and the statistical (thermal) broadening of the 2p-3d transitions have been investigated as a function of the atomic number Z. It appears that at the conditions of the experiment the role of the term and configuration broadening was different in the three analyzed elements, this broadening being sensitive to the atomic number. Some effects of the temperature gradients and possible non-LTE effects have been studied with the help of the radiative collisional code SCRIC. The sensitivity of the 2p-3d structures with respect to temperature and density in medium-Z plasmas may be helpful for diagnostics of LTE plasmas especially in future experiments on the Deltan=0 absorption in medium-Z plasmas for astrophysical applications. PMID- 22060514 TI - Strongly coupled regime of ionization-induced scattering in ultrashort laser matter interactions. AB - The ionization-induced scattering of an ultrashort laser pulse is investigated by means of direct modeling of the Maxwell equations. Our results reveal a strongly coupled regime of ionization-induced scattering where structural and temporal characteristics of the laser-matter interactions may change significantly. In this regime, small-scaled plasma inhomogeneities are effectively generated with high plasma densities, even exceeding the critical one. PMID- 22060515 TI - Wakefield generation in magnetized plasmas. AB - We consider wakefield generation in plasmas by electromagnetic pulses propagating perpendicular to a strong magnetic field, in the regime where the electron cyclotron frequency is equal to or larger than the plasma frequency. Particle-in cell simulations reveal that for moderate magnetic field strengths previous results are reproduced, and the wakefield wave number spectrum has a clear peak at the inverse skin depth. However, when the cyclotron frequency is significantly larger than the plasma frequency, the wakefield spectrum becomes broadband, and simultaneously the loss rate of the driving pulse is much enhanced. A set of equations for the scalar and vector potentials reproducing these results are derived, using only the assumption of a weakly nonlinear interaction. PMID- 22060516 TI - Fourier-mode dynamics for the nonlinear Schrodinger equation in one-dimensional bounded domains. AB - We analyze the 1D focusing nonlinear Schrodinger equation in a finite interval with homogeneous Dirichlet or Neumann boundary conditions. There are two main dynamics, the collapse which is very fast and a slow cascade of Fourier modes. For the cubic nonlinearity the calculations show no long-term energy exchange between Fourier modes as opposed to higher nonlinearities. This slow dynamics is explained by fairly simple amplitude equations for the resonant Fourier modes. Their solutions are well behaved so filtering high frequencies prevents collapse. Finally, these equations elucidate the unique role of the zero mode for the Neumann boundary conditions. PMID- 22060517 TI - Strong collapse turbulence in a quintic nonlinear Schrodinger equation. AB - We consider the quintic one-dimensional nonlinear Schrodinger equation with forcing and both linear and nonlinear dissipation. Quintic nonlinearity results in multiple collapse events randomly distributed in space and time, forming forced turbulence. Without dissipation each of these collapses produces finite time singularity, but dissipative terms prevent actual formation of singularity. In statistical steady state of the developed turbulence, the spatial correlation function has a universal form with the correlation length determined by the modulational instability scale. The amplitude fluctuations at that scale are nearly Gaussian while the large-amplitude tail of the probability density function (PDF) is strongly non-Gaussian with powerlike behavior. The small amplitude nearly Gaussian fluctuations seed formation of large collapse events. The universal spatiotemporal form of these events together with the PDFs for their maximum amplitudes define the powerlike tail of the PDF for large-amplitude fluctuations, i.e., the intermittency of strong turbulence. PMID- 22060518 TI - Programmed buckling by controlled lateral swelling in a thin elastic sheet. AB - Recent experiments have imposed controlled swelling patterns on thin polymer films, which subsequently buckle into three-dimensional shapes. We develop a solution to the design problem suggested by such systems, namely, if and how one can generate particular three-dimensional shapes from thin elastic sheets by mere imposition of a two-dimensional pattern of locally isotropic growth. Not every shape is possible. Several types of obstruction can arise, some of which depend on the sheet thickness. We provide some examples using the axisymmetric form of the problem, which is analytically tractable. PMID- 22060519 TI - Anderson localization and Brewster anomalies in photonic disordered quasiperiodic lattices. AB - A comprehensive study of the properties of light propagation through one dimensional photonic disordered quasiperiodic superlattices, composed of alternating layers with random thicknesses of air and a dispersive metamaterial, is theoretically performed. The superlattices consist of the successive stacking of N quasiperiodic Fibonacci or Thue-Morse heterostructures. The width of the slabs in the photonic superlattice may randomly fluctuate around its mean value, which introduces a structural disorder into the system. It is assumed that the left-handed layers have a Drude-type dispersive response for both the dielectric permittivity and magnetic permeability, and Maxwell's equations are solved for oblique incidence by using the transfer-matrix formalism. The influence of both quasiperiodicity and structural disorder on the localization length and Brewster anomalies are thoroughly discussed. PMID- 22060520 TI - Fractional-calculus model for temperature and pressure waves in fluid-saturated porous rocks. AB - We study a fractional time derivative generalization of a previous Natale-Salusti model about nonlinear temperature and pressure waves, propagating in fluid saturated porous rocks. Their analytic solutions, i.e., solitary shock waves characterized by a sharp front, are here generalized, introducing a formalism that allows memory mechanisms. In realistic wave propagation in porous media we must take into account spatial or temporal variability of permeability, diffusivity, and other coefficients due to the system "history." Such a rock fracturing or fine particulate migration could affect the rock and its pores. We therefore take into account these phenomena by introducing a fractional time derivative to simulate a memory-conserving formalism. We also discuss this generalized model in relation to the theory of dynamic permeability and tortuosity in fluid-saturated porous media. In such a realistic model we obtain exact solutions of Burgers' equation with time fractional derivatives in the inviscid case. PMID- 22060521 TI - Discrete breathers on symmetry-determined invariant manifolds for scalar models on the plane square lattice. AB - A group-theoretical approach for studying localized periodic and quasiperiodic vibrations in two- and three-dimensional lattice dynamical models is developed. This approach is demonstrated for the scalar models on the plane square lattice. The symmetry-determined invariant manifolds admitting existence of localized vibrations are found, and some types of discrete breathers are constructed on these manifolds. A general method using the apparatus of matrix representations of symmetry groups to simplify the standard linear stability analysis is discussed. This method allows one to decompose the corresponding system of linear differential equations with time-dependent coefficients into a number of independent subsystems whose dimensions are less than the full dimension of the considered system. PMID- 22060522 TI - Gap compactonlike solutions of coupled Kortweg-de Vries equations with linear and nonlinear dispersions. AB - We show the existence of a type of excitation, which we term as "gap compactonlike," within the gap of the linear spectrum of a system of coupled Kortweg-de Vries equations with linear and nonlinear dispersions. Since the solutions lie in the gap region of the spectra, they avoid resonance with the linear oscillatory wave and, therefore, do not decay into radiations. These types of solutions are important in energy localization and transport in polymers and biopolymers, optical systems, etc. PMID- 22060523 TI - Parallel-tempering cluster algorithm for computer simulations of critical phenomena. AB - In finite-size scaling analyses of Monte Carlo simulations of second-order phase transitions one often needs an extended temperature range around the critical point. By combining the parallel-tempering algorithm with cluster updates and an adaptive routine to find the temperature window of interest, we introduce a flexible and powerful method for systematic investigations of critical phenomena. As a result, we gain one to two orders of magnitude in the performance for two- and three-dimensional Ising models in comparison with the recently proposed Wang Landau recursion for cluster algorithms based on the multibondic algorithm, which is already a great improvement over the standard multicanonical variant. PMID- 22060524 TI - Preventing the recurrence effect in the Vlasov simulation by randomizing phase point velocities in phase space. AB - The Vlasov equation is simulated by following the characteristics of phase points in phase space. It is shown that by increasing the number of phase points, without enhancing the resolution of phase-space grid, the accuracy of the simulation will be improved. In addition, the phase-point spacing introduces a smaller scale than grid spacing on which fine structures might be more conveniently handled. In order to perform simulation with a large population of phase points, an alternative to the bilinear interpolation scheme is introduced that reduces the number of operations. It is shown that by randomizing initial phase-point velocities, the recurrence effect does not happen. Finally, the standard problem of linear and nonlinear Landau damping will be examined. PMID- 22060525 TI - Consistent pseudopotential interactions in lattice Boltzmann models. AB - We outline a systematic procedure on how to construct and derive interactions for nonideal lattice fluids. Using a mesoscopic approach based on exact lattice theories, we prove the consistency of the resulting diffuse interface theory with continuum thermodynamics. Translated in the framework of the so called "Shan Chen" model for nonideal lattice fluids, this paper shows how to adjust the associated pseudopotentials to reproduce a free energy model based on a square gradient theory of equilibrium interfaces. PMID- 22060526 TI - Axisymmetric lattice Boltzmann method revised. AB - A reformulated lattice Boltzmann model is described for incompressible axisymmetric flows with or without swirling. It is a further development and improvement on the author's axisymmetric lattice Boltzmann method. The main features of the revised scheme are (a) all the macroscopic variables such as velocities are determined in the same formulas as those in the conventional lattice Boltzmann approach to the Navier-Stokes equations and (b) the added sink or source and force terms are simple with no calculation for a derivative. Such features distinguish the present method from the other existing simplified schemes, leading to a simple and efficient model. The scheme is naturally suitable for generic incompressible axisymmetric rotational flows involving more physical phenomena. The numerical solutions to Womersley and cylindrical cavity flows are presented to demonstrate its accuracy and capability. PMID- 22060527 TI - Lagrange-mesh calculations and Fourier transform. AB - The Lagrange-mesh method is a very accurate procedure for computing eigenvalues and eigenfunctions of a two-body quantum equation written in the configuration space. Using a Gauss quadrature rule, the method only requires the evaluation of the potential at some mesh points. The eigenfunctions are expanded in terms of regularized Lagrange functions, which vanish at all mesh points except one. Using the peculiarities of the method, it is shown that the Fourier transform of the eigenfunctions, computed in the configuration space, can easily be obtained with good accuracy in the physical domain of the momentum space. Also, observables in this space can easily be computed with good accuracy only using matrix elements and eigenfunctions computed in the configuration space. PMID- 22060528 TI - Entropic algorithms and the lid method as exploration tools for complex landscapes. AB - Monte Carlo algorithms such as the Wang-Landau algorithm and similar "entropic" methods are able to accurately sample the density of states of model systems and thereby give access to thermal equilibrium properties at any temperature. Thermal equilibrium is, however, unachievable at low temperatures in glassy systems. Such systems are characterized by a multitude of metastable configurations pictorially referred to as "valleys" of an energy landscape. Geometrical properties of the landscape, e.g., the local density of states describing the distribution in energy of the states belonging to a single valley, are key to understanding the dynamical properties of such systems. In this paper we combine the lid algorithm, a tool for landscape exploration previously applied to a range of models, with the Wang-Swendsen algorithm. To test this improved exploration tool, we consider a paradigmatic complex system, the Edwards-Anderson model in two and three spatial dimensions. We find a striking difference between the energy dependence of the local density of states in two dimensions and three dimensions--nearly linear in the first case, and nearly exponential in the second. The dynamical consequences of these findings are discussed. PMID- 22060529 TI - Local absorbing boundary conditions for nonlinear wave equation on unbounded domain. AB - The numerical solution of the nonlinear wave equation on unbounded spatial domain is considered. The artificial boundary method is introduced to reduce the nonlinear problem on unbounded spatial domain to an initial boundary value problem on a bounded domain. Using the unified approach, which is based on the operator splitting method, we construct the efficient nonlinear local absorbing boundary conditions for the nonlinear wave equation, and give the stability analysis of the resulting boundary conditions. Finally, several numerical examples are given to demonstrate the effectiveness of our method. PMID- 22060530 TI - Coarse graining the dynamics of heterogeneous oscillators in networks with spectral gaps. AB - We present a computer-assisted approach to coarse graining the evolutionary dynamics of a system of nonidentical oscillators coupled through a (fixed) network structure. The existence of a spectral gap for the coupling network graph Laplacian suggests that the graph dynamics may quickly become low dimensional. Our first choice of coarse variables consists of the components of the oscillator states--their (complex) phase angles--along the leading eigenvectors of this Laplacian. We then use the equation-free framework, circumventing the derivation of explicit coarse-grained equations, to perform computational tasks such as coarse projective integration, coarse fixed-point, and coarse limit-cycle computations. In a second step, we explore an approach to incorporating oscillator heterogeneity in the coarse-graining process. The approach is based on the observation of fast-developing correlations between oscillator state and oscillator intrinsic properties and establishes a connection with tools developed in the context of uncertainty quantification. PMID- 22060531 TI - Connected-component identification and cluster update on graphics processing units. AB - Cluster identification tasks occur in a multitude of contexts in physics and engineering such as, for instance, cluster algorithms for simulating spin models, percolation simulations, segmentation problems in image processing, or network analysis. While it has been shown that graphics processing units (GPUs) can result in speedups of two to three orders of magnitude as compared to serial codes on CPUs for the case of local and thus naturally parallelized problems such as single-spin flip update simulations of spin models, the situation is considerably more complicated for the nonlocal problem of cluster or connected component identification. I discuss the suitability of different approaches of parallelization of cluster labeling and cluster update algorithms for calculations on GPU and compare to the performance of serial implementations. PMID- 22060532 TI - Simulation of continuous-time random walks by the pruned-enriched method. AB - We generalize the pruned-enriched method to simulate the probability distribution of the continuous-time random walk. The small probabilities that the pruned enriched method can simulate could be many orders of magnitude smaller than the minimum probability obtained from the particle-tracking method when the computational costs of the two methods are the same. In addition, we propose a new criterion for pruning enrichment to improve the efficiency of the pruned enriched method. PMID- 22060533 TI - Information filtering via biased heat conduction. AB - The process of heat conduction has recently found application in personalized recommendation [Zhou et al., Proc. Natl. Acad. Sci. USA 107, 4511 (2010)], which is of high diversity but low accuracy. By decreasing the temperatures of small degree objects, we present an improved algorithm, called biased heat conduction, which could simultaneously enhance the accuracy and diversity. Extensive experimental analyses demonstrate that the accuracy on MovieLens, Netflix, and Delicious datasets could be improved by 43.5%, 55.4% and 19.2%, respectively, compared with the standard heat conduction algorithm and also the diversity is increased or approximately unchanged. Further statistical analyses suggest that the present algorithm could simultaneously identify users' mainstream and special tastes, resulting in better performance than the standard heat conduction algorithm. This work provides a creditable way for highly efficient information filtering. PMID- 22060534 TI - Success-driven distribution of public goods promotes cooperation but preserves defection. AB - Established already in Biblical times, the Matthew effect refers to the fact that in societies the rich tend to get richer and the potent even more powerful. Here we investigate a game theoretical model describing the evolution of cooperation on structured populations where the distribution of public goods is driven by the reproductive success of individuals. Phase diagrams reveal that cooperation is promoted irrespective of the uncertainty by strategy adoptions and the type of interaction graph, yet the complete dominance of cooperators is elusive due to the spontaneous emergence of superpersistent defectors that owe their survival to extremely rare microscopic patterns. This indicates that success-driven mechanisms are crucial for effectively harvesting benefits from collective actions but that they may also account for the observed persistence of maladaptive behavior. PMID- 22060535 TI - Core-periphery disparity in fractal behavior of complex networks. AB - We show that there is a disparity in fractal scaling behavior of the core and peripheral parts of empirical small-world scale-free networks. We decompose the network into a core and a periphery and measure the fractal dimension of each part separately using the box-counting method. We find that the core of small world scale-free networks has a nonfractal structure, whereas the periphery exhibits either fractal or nonfractal scaling. The fractal dimension of the periphery is found to coincide with one for the whole network. PMID- 22060536 TI - Nearest neighbors, phase tubes, and generalized synchronization. AB - In this paper we report on the necessity of the refinement of the concept of generalized chaotic synchronization. We show that the state vectors of the interacting chaotic systems being in the generalized synchronization regime are related to each other by the functional, but not the functional relation as it was assumed until now. We propose the phase tube approach explaining the essence of generalized synchronization and allowing the detection and the study of this regime in many relevant physical circumstances. The finding discussed in this Brief Report provides great potential for different applications. PMID- 22060537 TI - Chaotic dynamics of a magnetic nanoparticle. AB - We study the deterministic spin dynamics of an anisotropic magnetic particle in the presence of a magnetic field with a constant longitudinal and a time dependent transverse component using the Landau-Lifshitz-Gilbert equation. We characterize the dynamical behavior of the system through calculation of the Lyapunov exponents, Poincare sections, bifurcation diagrams, and Fourier power spectra. In particular we explore the positivity of the largest Lyapunov exponent as a function of the magnitude and frequency of the applied magnetic field and its direction with respect to the main anisotropy axis of the magnetic particle. We find that the system presents multiple transitions between regular and chaotic behaviors. We show that the dynamical phases display a very complicated structure of intricately intermingled chaotic and regular phases. PMID- 22060538 TI - Vortices in a cylindrical annulus nonhomogeneously heated: effect of localized heating on their stability and intensity. AB - In this paper we study the influence of localized or widespread nonhomogeneous temperature profiles on the stability and intensity of vertical vortices generated in a cylindrical annulus by a convective instability. Localized profiles lead to more stable vortices while widespread inhomogeneities intensify the spin motion around the inner cylinder. PMID- 22060539 TI - Azimuthal solitary surface wave in cylindrical tank. AB - This Brief Report is devoted to the study of the solitary surface wave rotating in the azimuthal direction, arising during water drainage from a cylindrical reservoir, when shallow flow conditions are reached. The linear dependence between the wave speed and its amplitude is shown to be similar to that expected from the classical Korteweg-de Vries equation. PMID- 22060540 TI - Local wettability reversal during steady-state two-phase flow in porous media. AB - We study the effect of local wettability reversal on remobilizing immobile fluid clusters in steady-state two-phase flow in porous media. We consider a two dimensional network model for a porous medium and introduce a wettability alteration mechanism. A qualitative change in the steady-state flow patterns, destabilizing the percolating and trapped clusters, is observed as the system wettability is varied. When capillary forces are strong, a finite wettability alteration is necessary to move the system from a single-phase to a two-phase flow regime. When both phases are mobile, we find a linear relationship between fractional flow and wettability alteration. PMID- 22060541 TI - Electromagnetic solitary pulses in a magnetized electron-positron plasma. AB - A theory for large amplitude compressional electromagnetic solitary pulses in a magnetized electron-positron (e-p) plasma is presented. The pulses, which propagate perpendicular to the external magnetic field, are associated with the compression of the plasma density and the wave magnetic field. Here the solitary wave magnetic field pressure provides the restoring force, while the inertia comes from the equal mass electrons and positrons. The solitary pulses are formed due to a balance between the compressional wave dispersion arising from the curl of the inertial forces in Faraday's law and the nonlinearities associated with the divergence of the electron and positron fluxes, the nonlinear Lorentz forces, the advection of the e-p fluids, and the nonlinear plasma current densities. The compressional solitary pulses can exist in a well-defined speed range above the Alfven speed. They can be associated with localized electromagnetic field excitations in magnetized laboratory and space plasmas composed of electrons and positrons. PMID- 22060542 TI - Approaching a parameter-free metadynamics. AB - We present a unique derivation of metadynamics. This work leads to a more robust understanding of the error in the computed free energy than what has been obtained previously. Moreover, a formula for the exact free energy is introduced. The formula can be used to post-process any existing well-tempered metadynamics data, allowing one, in principle, to obtain an exact free energy regardless of the metadynamics parameters. PMID- 22060543 TI - Comment on "Lattice Boltzmann method for simulations of liquid-vapor thermal flows". AB - Zhang and Chen proposed a lattice Boltzmann method for simulations of liquid vapor thermal flows [Zhang and Chen, Phys. Rev. E 67, 066711 (2003)]. In their numerical test, the authors show simulation results with a temperature ratio of approximately 1.2 for a thermal two-phase flow with T<0.8T(c). However, we believe this to be erroneous and demonstrate the error to originate from a wrong choice of a parameter of critical importance in the Carnahan-Starling equation of state used in their work. Our numerical tests show that using the correct parameter choice, the scheme is only valid and robust to simulate temperature ratios below 1.10 and the lowest temperature in the flow field should be 0.85T(c). PMID- 22060545 TI - Treatment of patients with chronic lymphocytic leukemia with 17p deletion: the saga continues. PMID- 22060546 TI - Extracellular polysaccharide-degrading proteome of Butyrivibrio proteoclasticus. AB - Plant polysaccharide-degrading rumen microbes are fundamental to the health and productivity of ruminant animals. Butyrivibrio proteoclasticus B316(T) is a gram positive, butyrate-producing anaerobic bacterium with a key role in hemicellulose degradation in the rumen. Gel-based proteomics was used to examine the growth phase-dependent abundance patterns of secreted proteins recovered from cells grown in vitro with xylan or xylose provided as the sole supplementary carbon source. Five polysaccharidases and two carbohydrate-binding proteins (CBPs) were among 30 identified secreted proteins. The endo-1,4-beta-xylanase Xyn10B was 17.5 fold more abundant in the culture medium of xylan-grown cells, which suggests it plays an important role in hemicellulose degradation. The secretion of three nonxylanolytic enzymes and two CBPs implies they augment hemicellulose degradation by hydrolysis or disruption of associated structural polysaccharides. Sixteen ATP-binding cassette (ABC) transporter substrate-binding proteins were identified, several of which had altered relative abundance levels between growth conditions, which suggests they are important for oligosaccharide uptake. This study demonstrates that B. proteoclasticus modulates the secretion of hemicellulose-degrading enzymes and ATP-dependent sugar uptake systems in response to growth substrate and supports the notion that this organism makes an important contribution to polysaccharide degradation in the rumen. PMID- 22060547 TI - Implications of increased student intake on rural rotations in Australian medical schools. PMID- 22060548 TI - Molecular structure of the core-modified siRNA duplexes containing diastereomeric pair of [C6'(R)-OH]- versus [C6'(S)-OH]-carba-LNAs suggests a model for RNAi action. AB - Molecular structures of native and a pair of modified small interfering RNA-RNA duplexes containing carbocyclic [6 '-(R)-OH/7 '-(S)-methyl]- and [6 '-(S)-OH/7 ' (S)-methyl]-carba-LNA-thymine nucleotides, which are two diastereomeric analogs of the native T nucleotide, incorporated at position 13 in the antisense (AS) strand of siRNA, have been simulated using molecular mechanics/dynamics techniques. The main aim of the project has been to find a plausible structural explanation of why modification of siRNA at T(13) position by the [6 '(R)-O-(p Toluoyl)-7 '(S)-methyl]-carba-LNA-Thymine [IC(50) of 3.32 +/- 0.17 nM] is ca 24 times more active as an RNA silencing agent against the target HIV-1 TAR RNA than the [6 '(S)-O-(p-Toluoyl)-7 '(S)-methyl]-counterpart [IC(50) of 79.8 +/- 17 nM] [1]. The simulations reveal that introduction of both C6 '(R)-OH and C6 '(S)-OH stereoisomers does not lead even to local perturbation of the siRNA-RNA duplex structures compared to the native, and the only significant difference between 6 '(S)- and 6 '(R)-diastereomers found is the exposure of the 6 '-OH group of the 6 '(R)-diastereoisomer toward the edge of the duplex while the 6 '-hydroxyl group of the 6 '(S)-diastereoisomer is somewhat buried in the minor groove of the duplex. This rules out a hypothesis about any possible local distortion by the nature of chemical modification of the siRNA-target the RNA duplex, which might have influenced the formation of the effective RNA silencing complex (RISC) and puts some weight on the hypothesis about the 6 '-hydroxy group being directly involved with most probably Ago protein, since it is known from exhaustive X-ray studies [2, 3] that the core residues are indeed involved with hydrogen bonding with the internucleotidyl phosphates. Further systematic investigation is in progress to map the position-dependent functional and nonfunctional interactions of the modified [6 '(R or S)-O-(p-Toluoyl)-7 '(S)-methyl]-carba-LNA-T with the Ago2 protein of the RISC. PMID- 22060549 TI - Isolation and characterization of a murine P388 leukemia line resistant to clofarabine. AB - A murine P388 leukemia line fully resistant to clofarabine was obtained after only two courses of intraperitoneal treatment (three times a day for nine consecutive days). The resistance was stable for at least 13 weeks without treatment. The subline was as sensitive to 5-fluorouracil, methotrexate, cyclophosphamide, cisplatin, melphalan, BCNU, doxorubicin, etoposide, irinotecan, vincristine, and docetaxel as was the parental P388/0 line but was cross resistant to five antimetabolites [palmO-ara-C, 4'-thio-ara-C, fludarabine phosphate, cladribine, and gemcitabine-all of which require deoxycytidine kinase for activation] and paclitaxel. The subline had less than 1% of the deoxycytidine kinase activity in comparison to P388/0. PMID- 22060550 TI - The effect of ITPA polymorphisms on the enzyme kinetic properties of human erythrocyte inosine triphosphatase toward its substrates ITP and 6-Thio-ITP. AB - The role of inosine triphosphatase (ITPase) in adverse drug reactions associated with thiopurine therapy is still under heavy debate. Surprisingly, little is known about the way thiopurines are handled by ITPase. We studied the effect of ITPA polymorphisms on the handling of inosine triphosphate (ITP) and thioinosine triphosphate (TITP) to gain more insight into this phenomenon. Human erythrocyte ITPase activity was measured by incubation with ITP using established protocols, and the generated inosine monophosphate (IMP) was measured using ion-pair RP HPLC. Molecular analysis of the ITPA gene was performed to establish the genotype. Kinetic parameters were established for the two common polymorphisms for both ITP and TITP as substrates using the above mentioned protocol. Both ITP and TITP are substrates for ITPase and their enzyme activities are comparable. Substrate binding is not altered in the different ITPA polymorphisms. It is shown that the velocity of pyrophosphohydrolysis is compromised when the c.94C > A polymorphism is present, both in the heterozygous and in the homozygous state. TITP is handled by ITPase in a similar way as for ITP, which implies that TITP will accumulate in the erythrocytes of patients with an ITPase deficiency, resulting in adverse drug reactions (ADRs) on thiopurine therapy. In carriers of ITPA polymorphisms, the matter is more complex and the development of ADR may depend on additional epigenetic factors rather than on the accumulation of thiopurinenucleotides. PMID- 22060551 TI - Synthesis and evaluation of oligonucleotide-conjugated pyrrole polyamide-2' deoxyguanosine hybrids as novel gene expression control compounds. AB - DNA oligonucleotide-conjugated pyrrole polyamide-2'-deoxyguanosine hybrids were synthesized and examined as novel gene expression control compounds. The T(m) values and circular dichroism spectral analyses showed that the oligonucleotide conjugated hybrids possess high DNA recognition and a very high binding affinity for DNA that includes the pyrrole polyamide binding sequence. PMID- 22060552 TI - In-vitro cytotoxicity and cell cycle analysis of two novel bis-1,2, 4-triazole derivatives: 1,4-bis[5-(5-mercapto-1,3,4-oxadiazol-2-yl-methyl)-thio-4-(p-tolyl) 1,2,4-triazol-3-yl]-butane (MNP-14) and 1,4-bis[5-(carbethoxy-methyl)-thio-4-(p ethoxy phenyl)-1,2,4-triazol-3-yl]-butane (MNP-16). AB - In the present study, we have tested the cytotoxic and DNA damage activity of two novel bis-1,2,4 triazole derivatives, namely 1,4-bis[5-(5-mercapto-1,3,4 oxadiazol-2-yl-methyl)-thio-4-(p-tolyl)-1,2,4-triazol-3-yl]-butane (MNP-14) and 1,4-bis[5-(carbethoxy-methyl)-thio-4-(p-ethoxy phenyl) -1,2,4-triazol-3-yl] butane (MNP-16). The effect of these molecules on cellular apoptosis was also determined. The in-vitro cytotoxicity was evaluated by a 3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyl tetrazolium bromide (MTT) assay as well as Trypan blue dye exclusion methods against human acute lymphoblastic leukemia (MOLT4) and lung cancer cells (A549). Our results showed that MNP-16 induced significant cytotoxicity (IC(50) of 3-5 MUM) compared with MNP-14. The cytotoxicity induced by MNP-16 was time and concentration dependent. The cell cycle analysis by flow cytometry (fluorescence-activated cell sorting [FACS]) revealed that though there was a significant increase in the apoptotic population (sub-G(1) phase) with an increased concentration of MNP-14 and 16, there was no cell cycle arrest. Further, the comet assay results indicated considerable DNA strand breaks upon exposure to these compounds, thereby suggesting the possible mechanism of cytotoxicity induced by MNP-16. Hence, we have identified a novel molecule (MNP 16) which could be of great clinical relevance in cancer therapeutics. PMID- 22060553 TI - Synthesis of stable isotope labeled analogs of the anti-hepatitis C virus nucleotide prodrugs PSI-7977 and PSI-352938. AB - In order to support bioanalytical LC/MS method development and plasma sample analysis in preclinical and clinical studies of the anti-hepatitis C-virus nucleotides, PSI-7977 and PSI-352938, the corresponding stable isotope labeled forms were prepared. These labeled compounds were prepared by addition reaction of the freshly prepared Grignard reagent (13)CD(3)MgI to the corresponding 2 ' ketone nucleosides followed by fluorination of the resulting carbinol with DAST. As expected, these 2 '-C-(trideuterated-(13)C-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones. PMID- 22060554 TI - Synthesis and biological activity of bimorpholine and its carbanucleoside. AB - A new enantiomerically pure carbacyclic nucleoside analogue with bimorpholine as a nonaromatic nucleobase was synthesized. The nucleoside analogue and bimorpholine were tested for cytotoxicity using an MTT assay and the xCELLigence System. Both assays revealed that compound 3 was highly cytotoxic at a 50 MUM concentration while the cytotoxic effect of compound 1 was much less prominent. No antiretroviral activity was detected for this compound. In contrast, it acted as a potent inhibitor of hepatitis C virus (HCV) replication. Most likely this effect originates largely from the cytotoxicity of the compound; however, it is possible that a specific mechanism of HCV inhibition also exists. PMID- 22060555 TI - An HPLC-based assay of adenylosuccinate lyase in erythrocytes. AB - ADSL deficiency is a disorder of purine metabolism with a broad clinical spectrum. A rapid and simple HPLC-based assay to measure ADSL activity in erythrocytes was developed. The suitability of DBSs was assessed. ADSL activity was measured in erythrocyte lysates and DBS using succinyl-AMP as the substrate. Detection and quantification were performed using isocratic ion-pairing reversed phase HPLC with UV-detection. Reference values in erythrocyte lysates were established. The intra- and interassay variations were 2% and 8%, respectively. ADSL deficiency was easily recognized. ADSL activity in DBS was highly unstable, disqualifying DBS for diagnostic procedures. PMID- 22060556 TI - DNA systems for B-Z transition and their significance as epigenetic model: the fundamental role of the methyl group. AB - Epigenetic systems involved in the dynamics of gene expression, which are fundamental to cell determination and function without alteration in DNA sequences, are based on methylation of the N-terminal tails of lysine residues and DNA methylation. We demonstrate the vital importance for genetic transfer by different (hydrogen) networks, suggesting a complex interaction between the two epigenetic modifications. In other words, the methylation of local lysines can prescribe C(P)G methylation, which requires that methylation of histones and DNA are cooperative in carrying out an epigenetic instruction for integrating gene silencing networks. To give a bio-organic description of the epigenetic coherence between histone and base methylation, we used the well-known B- into Z-DNA dynamics in combination with the unique properties of phosphatemethylated DNA on different levels of chemistry. PMID- 22060557 TI - Synthesis of novel difluoro-cyclopropyl guanine nucleosides and their phosphonate analogues as potent antiviral agents. AB - The synthesis of new rigid guanine analogues with anti-HIV-1 and anti-herpes viral activities is described. The phosphonate of difluorocyclopropane nucleoside analogue 26 exhibits in vitro anti-HIV-1 activity similar to that of PMEA in MT-4 cells. Further, analogue 20 shows moderate anti-HCMV activity in MRC cells. PMID- 22060558 TI - Synthesis and characterization of C8 analogs of c-di-GMP. AB - We have synthesized five analogs of c-di-GMP with different substituents at the guanine C8 position, to study their effects on the metal-dependent polymorphism we had previously demonstrated for the parent compound. Of these, only the K(+) salt of c-di-Br-GMP, 2, forms higher order complexes, predominantly two different syn octamolecular ones. Its Na(+) salt, as well as both the K(+) and Na(+) salts of c-di-thio-GMP, 3, c-di-methylthio-GMP, 4, c-di-phenyl-GMP, 5, and c-di acetylphenyl-GMP, 6, all form primarily a syn bimolecular structure. PMID- 22060559 TI - Nontemplate polymerization of free nucleotides into genetic elements by thermophilic DNA polymerase in vitro. AB - DNA synthesis is the cornerstone of all life forms and is required to replicate and restore the genetic information. Usually, DNA synthesis is carried out only by DNA polymerases semiconservatively to copy preexisting DNA templates. We report here that DNA strands were synthesized ab initio in the absence of any DNA or RNA template by thermophilic DNA polymerases at (a) a constant high temperature (74 degrees C), (b) alternating temperatures (94 degrees C/60 degrees C/74 degrees C), or (c) physiological temperatures (37 degrees C). The majority of the ab initio synthesized DNA represented short sequence blocks, repeated sequences, intergenic spacers, and other unknown genetic elements. These results suggest that novel DNA elements could be synthesized in the absence of a nucleic acid template by thermophilic DNA polymerases in vitro. Biogenesis of genetic information by thermophilic DNA polymerase-mediated nontemplate DNA synthesis may explain the origin of genetic information and could serve as a new way of biosynthesis of genetic information that may have facilitated the evolution of life. PMID- 22060560 TI - Synthesis of new 9-glycosyl-4,9-dihydropyrano [3,4-b]indole-1(3H)-ones as antibacterial agents. AB - A series of new 9-glycosyl-4,9-dihydropyrano[3,4-b]indole-1(3H)-ones 3 was synthesized in moderate to low yields. 4,9-Dihydropyrano[3,4-b]indole-1(3H)-ones (1) were coupled with different acetobromoglycopyranoses 2 in refluxing toluene in the presence of silver oxide to afford one coupling product of the respective N-glycosides. alpha-L-Arabinopyranosides 3j and 3m were the most active glycosides among the tested compounds against certain Gram positive and Gram negative bacterial strains. PMID- 22060561 TI - Dynamic proteome analysis of Cyanothece sp. ATCC 51142 under constant light. AB - Understanding the dynamic nature of protein abundances provides insights into protein turnover not readily apparent from conventional, static mass spectrometry measurements. This level of data is particularly informative when surveying protein abundances in biological systems subjected to large perturbations or alterations in environment such as cyanobacteria. Our current analysis expands upon conventional proteomic approaches in cyanobacteria by measuring dynamic changes of the proteome using a (13)C(15)N-l-leucine metabolic labeling in Cyanothece ATCC51142. Metabolically labeled Cyanothece ATCC51142 cells grown under nitrogen-sufficient conditions in continuous light were monitored longitudinally for isotope incorporation over a 48 h period, revealing 414 proteins with dynamic changes in abundances. In particular, proteins involved in carbon fixation, pentose phosphate pathway, cellular protection, redox regulation, protein folding, assembly, and degradation showed higher levels of isotope incorporation, suggesting that these biochemical pathways are important for growth under continuous light. Calculation of relative isotope abundances (RIA) values allowed the measurement of actual active protein synthesis over time for different biochemical pathways under high light exposure. Overall results demonstrated the utility of "non-steady state" pulsed metabolic labeling for systems-wide dynamic quantification of the proteome in Cyanothece ATCC51142 that can also be applied to other cyanobacteria. PMID- 22060563 TI - Genetic and nutritional effects on the fatty acid composition of subcutaneous and intramuscular lipids of steers. AB - Genetic and nutritional influences on fatty acid composition of subcutaneous (SNL) and intramuscular neutral lipids (IMNL) and intramuscular phospholipids (IMPL) of steer carcasses were investigated by removing the effect of carcass fat percentage (CFP) or slaughter age (SA) on the fatty acid composition. To investigate the genetic influences, steer progenies from two dam breed-types (Japanese Black (JB) and f(1) between JB bull and Holstein cows) and three different maturing types of JB sires were used. Dam breed-type did not affect any of the fatty acids except 17:0 in SNL and none of those in IMNL. Percentages of 16:0, 16:1, 18:2, SFA, MUFA and PUFA in SNL differed among sires of JB dam breed type group (p < 0.05) even after removing the effect of CFP. Studies on the effects of two nutritional planes [high(H) and medium-high(MH)] on the fatty acid composition of SNL, IMNL and IMPL were done using JB steers. The SNL and IMNL of the H plane steers contained greater percentages of saturated fatty acids at the same CFP but less at the same SA than the MH plane animals. The reverse was true for the unsaturated fatty acid contents. PMID- 22060562 TI - Clinical significance of hyperglycaemia in acute coronary syndrome patients. AB - BACKGROUND: The clinical significance of moment measurements (admission and fasting glycaemia), persistent (hyperglycaemic index, HGI; time average glucose, TAG; mean glucose; maximum glucose) or chronic hyperglycaemia (HbA1c), estimated average glucose, eAG) is still elusive in clinical practice. AIM: To identify the clinical significance of hyperglycaemia in ACS. METHODS: The study included 226 consecutive patients with ACS. Indicators for hyperglycaemia were defined, calculated and a correlation analysis with standard parameters-EF, maximum CPK, maximum CPK-MB and troponin was performed. Patients were followed up for 12 months. RESULTS: Indicators for persistent and chronic hyperglycaemia correlated neither to ejection fraction, nor to the enzymes for myocardial necrosis (P > 0.05). In contrast, acute hyperglycaemia correlated negatively with ventricular systolic dysfunction (P = 0.001/0.007) and positively with maximum CPK, MB and troponin (P = 0.0001/0.008). TAG was an independent predictor for 6-month re hospitalization (P = 0.027) because of cardiac complications. CONCLUSION: Glycaemia at admission and fasting glucose could be used as metabolic surrogate markers for ventricular systolic dysfunction and TAG as an independent surrogate marker for six-month re-hospitalization. None of the indicators for hyperglycaemia could be used as independent prognostic factors for survival. Hyperglycaemia rather reflects an underlying impairment in glucose metabolism. PMID- 22060564 TI - Use of mutagenically separated PCR for the detection of the mutation associated with porcine stress syndrome. AB - A point mutation in the Ryr1 gene encoding the ryanodine receptor in porcine skeletal muscle is associated with enhanced growth characteristics and leanness but also with porcine stress syndrome and pale, soft exudative meat in some animals. The current diagnostic test for the mutation is based on the polymerase chain reaction (PCR), followed by a restriction enzyme digestion step, prior to agarose gel electrophoresis. Using a technique known as mutagenically separated PCR (MS-PCR), a one-step procedure for the identification of the point mutation associated with porcine stress syndrome has been developed. This removes the requirement of the current PCR-based test for restriction enzyme digestion, is consequently quicker to perform, and may lend itself more readily to automation. DNA from blood samples from a series of animals were genotyped using both the conventional test and MS-PCR, and complete agreement between the two methods was obtained. PMID- 22060565 TI - Design of product as source of variance in composition of meat-based infant beikosts. AB - The influence of both the design of the product (formulated raw ingredients) and type of product (on the meat type formulated base) on the mineral composition, crude protein (CP), protein digestibility (PD), total dietary fiber (TDF) and phytic acid (FA) contents of meat-based infant beikosts was studied. The product design was the main factor determining the CP, TDF, Ca, Na and K contents, while the type of product was the main factor determining the PD, FA, Zn, Fe and Mn contents. High K and Mn levels were related to high TDF contents. CP and Zn showed a significant relationship but the CP Fe relationship was not significant. PMID- 22060566 TI - Antioxidant enzyme activities in beef in relation to oxidation of lipid and myoglobin. AB - Lipid- and oxy-free radical generation has been implicated in oxidative processes which occur during meat maturation but the importance of the antioxidant enzyme (AOE) activity in these processes is not known. It was shown that metmyoglobin (MetMb) % and lipofuscin content were higher in colour-unstable muscles such as psoas major (PM) and diaphragma (D) compared to longissimus lumborum (LL) and tensor fasciae latae (TFL). Although Superoxide dismutase (SOD) activity is higher post mortem in PM and D muscles than in LL and TFL muscles, catalase and glutathione peroxidase (GPx) activities were higher only in D muscle. The higher AOE activity in colour-unstable muscles such as PM and D was not sufficient to prevent increased formation of MetMb and lipofuscin in these muscles compared to LL and TFL muscles. PMID- 22060567 TI - High pressure effects on lipid oxidation in minced pork. AB - Washed muscle fibres and minced pork were subjected to high pressure treatment at 800 MPa for 20 min at 20 degrees C prior to storage at 4 degrees C. In both cases, high pressure treated samples oxidised more rapidly than the controls, as measured by 2-thiobarbituric (TBA) number. The rate of lipid oxidation of the high pressure treated samples was similar to that induced by heat (80 degrees C for 15 min). No significant increased rate of oxidation was observed in minced meat samples treated at 300 MPa but above this pressure the rate increased with intensity. Minced meat samples pressure treated in air had higher initial TBA numbers than those treated in nitrogen, but upon storage both oxidised more rapidly than untreated samples. Differential scanning calorimetry, reflectance spectrophotometry and electrophoresis showed that treatment above 300-400 MPa caused marked denaturation of the myofibrillar and sarcoplasmic proteins and conversion of reduced myoglobin/oxymyoglobin to the denatured ferric form. The possible role of these reactions in catalysing lipid oxidation is discussed. PMID- 22060568 TI - The influence of the anticaking agent potassium ferrocyanide and salt on the oxidative stability of frozen minced pork meat. AB - The anticaking agent potassium ferrocyanide, K(4)Fe(CN)(6), was found to affect lipid oxidation in frozen, minced pork meat both in 'normal' concentrations, when added together with food grade salt to yield 2 % NaCl in the product, and in 'unrealistic' high concentrations added separately or together with analytical grade salt. The level of K(4)Fe(CN)(6) obtained from adding 2 % food grade salt accelerated the development of lipid hydroperoxides, but affected the development of TBARS to a lesser degree. High level of K(4)Fe(CN)(6) seems to protect hydroperoxides from degradation to secondary lipid oxidation products measured as TBARS. The use of salt with the anticaking agent, K(4)Fe(CN)(6), in meat processing should be reconsidered for each product since it may enhance lipid oxidation. A mechanism for mediation by the Fe(CN) (6)(4-)Fe(CN) (6)(3-) redox couple of pigment-catalysed lipid oxidation is suggested, based on an observed correlation between oxymyoglobin oxidation (measured as tristimulus colorimetric parameter, a) and lipid oxidation (measured as TBARS) for the frozen pork patties. PMID- 22060569 TI - Effects of high pressure treatment on Mg-enhanced ATPase activity of rabbit myofibrils. AB - Effects of high pressure treatment on the Mg-enhanced ATPase activity of myofibrils were studied to investigate the pressure-induced modification of actin myosin interaction. In the myofibrils prepared from muscles, similarities in the changes in the Mg-enhanced ATPase activity and its sensitivity to ionic strength were observed between muscles pressurized up to 200 MPa and muscles conditioned for 7 days. The BIMA (Biological Index of Myofibrillar Ageing) value of the pressurized myofibrils reached the same level as that of the conditioned myofibrils. When the isolated myofibrils were pressurized, slight increases of ATPase activity below 0.2 m KCI and of BIMA value were observed in the myofibrils pressurized at 30 MPa, which then decreased with increasing pressure. The release of soluble materials from the myofibrils was markedly accelerated by pressurization above 150 MPa. The SDS-PAGE analysis showed that the release of the constituents of thin filaments seemed to proceed prior to the release of the constituents of thick filaments. The pressure-induced changes in Mg-ATPase activity and BIMA value are explained in terms of the structural change of thin filaments resulting from briefly exposing muscles to high pressure. PMID- 22060570 TI - Effects of time on feed and post-mortem aging on palatability and lipid composition of crossbred Wagyu beef. AB - Twenty-seven Wagyu-sired steers were fed for 90 (14 steers) or 170 (13 steers) days to study the effects of time on feed on palatability and fatty acid composition, and the effects of post-mortem aging time (2, 4 or 10 days) on palatability. Hot carcass weight, fat thickness, longissimus dorsi muscle area, yield grade, estimated kidney, pelvic and heart fat and maturity score were increased (p < 0.05) by an additional 80 days on the high concentrate feed, but marbling was not changed (p > 0.05). Feeding the high concentrate diet for 170 days increased Warner-Bratzler shear force values (p < 0.05) and tended to decrease tenderness (p > 0.05), flavor intensity and connective tissue scores. For the 90 day feeding group, 4 days of aging improved connective tissue score (p < 0.05) and tended to increase (p > 0.05) tenderness scores and decrease shear force, compared with 2 days of aging. For the 170 day feeding group, 10 days of aging improved (p < 0.05) shear force and all sensory attributes except flavor intensity, compared to 2 days of aging. An additional 80 days on feed decreased (p < 0.05) stearic acid and total saturated fatty acids (SFA) and generally increased (p < 0.05) monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), MUFA:SFA, and PUFA:SFA in subcutaneous fat and longissimus dorsi muscle. The cholesterol content of fat and muscle increased (p < 0.05) as time on feed increased. Ninety days on a high concentrate diet was adequate for yearling crossbred Wagyu steers to produce highly acceptable carcasses. The additional 80 days on feed produced little or no overall benefit and the steers became overfinished and less tender. Ten days post-mortem aging improved (p < 0.05) all palatability attributes except flavor intensity. PMID- 22060571 TI - Effects of breed and sire on carcass characteristics and fatty acid profiles of crossbred wagyu and angus steers. AB - In a two-year experiment, 54 steers sired by seven Wagyu bulls [American Wagyu Association (AWA) sire numbers 331, 384, 388, 411, 429, 433 and 488] and 15 steers sired by two Angus bulls, all out of Angus-Hereford cows, were used to evaluate the effects of sire and breed on carcass characteristics and fatty acid composition. Steers were given ad-libitum access to a high-concentrate diet (15 % alfalfa cubes and 85 % barley supplement) for at least 170 days. Breed and individual sire effects were analysed. Wagyu-sired steers had higher marbling, maturity and quality scores, more estimated kidney, pelvic and heart fat, larger longissimus dorsi muscle areas, lower fat thicknesses and yield grades than Angus sired steers (p < 0.05). Steers sired by 388, 411 and 433 had lower fat thicknesses than steers sired by Angus, 429 and 488 (p < 0.05). Steers sired by 384 and 388 had higher marbling scores per cm subcutaneous fat than steers sired by Angus, 429 and 488, and lower fat thickness per 100 kg of carcass weight than Angus-sired steers (p < 0.05). For both subcutaneous fat and longissimus dorsi muscle, Wagyu-sired steers had higher (p < 0.05) percentages of 14:0, 14:1, 16:0, 16:1, and lower percentages of 18:0 than Angus-sired steers. The genetic differences in carcass characteristics among Wagyu sires may enable us to select for improved marbling with less fat in the Wagyu breed. Some statistically significant (p < 0.05) but small differences existed in fatty acid profiles between breeds and among sires. PMID- 22060572 TI - Effect of cooking and storage on lipid oxidation and development of cholesterol oxidation products in water buffalo meat. AB - Buffalo meat was subjected to two cooking methods viz. broiling and pressure cooking and two storage procedures viz. refrigerated (4 degrees C) storage for six days and frozen (-10 degrees C) storage for 90 days. Changes in lipid oxidation and development of cholesterol oxidation products were studied in raw as well as cooked meat samples. Total lipid, phospholipid, cholesterol, free fatty acid, glycolipid and glyceride contents increased significantly on cooking of meat but did not show any significant changes during either refrigerated or frozen storage except for free fatty acid content which showed an increase. The TBA values also increased during storage but not to the extent of indicating rancidity. Cholesterol oxidation products separated by thin layer chromatography were: cholestanetriol, 7-alpha-hydroxycholesterol, 19-hydroxycholesterol, 7 ketocholesterol, cholesterol-alpha-epoxide, cholesterol-beta-epoxide and an unidentified fraction. All these fractions, except for the unidentified fraction, increased on cooking and storage. The cholesterol-beta-epoxide fraction was resistant to changes. Changes in broiled meat were more pronounced compared to pressure cooked meat. Frozen storage did not prevent the development of cholesterol oxidation products in buffalo meat. PMID- 22060573 TI - The enumeration of coliforms and E. Coli on naturally contaminated beef: A comparison of the petrifilm(TM) method with the Australian Standard. AB - Petrifilm(TM) PEC was compared to Australian Standard (AS) methods for the enumeration of coliforms and Escherichia coli on 50 naturally contaminated beef samples from three meat works. The standard methods consist of a 3-tube most probable number test or a direct plate count on tryptone bile agar for E. coli, and violet red bile agar and the most probable number test for conliorms (AS 1766.2.12.1984 and AS 1766.2.3.1992). No significant difference was found between the methods, except that the count of E. coli on the direct plate method with a resuscitation step was significantly higher than the count on Petrifilm(TM), most probable number or direct plate count without resuscitation. PMID- 22060574 TI - Lipid oxidation and cholesterol oxidation in mutton during cooking and storage. AB - The effects of cooking viz. pressure-cooking and broiling and storage at 4 degrees C for six days and -10 degrees C for 90 days on lipid oxidation and development of cholesterol oxidation products in mutton were studied. Results revealed that cooking of meat significantly increased the total lipids, phospholipids, cholesterol, glycolipids, free fatty acids and glycerides, but they did not change during refrigerated and frozen storage. The TBA values increased on cooking and during storage. However, the values were below the threshold level for rancidity development. The following cholesterol oxidation products were separated by thin layer chromatography cholestanetriol, 7-alpha hydroxy cholesterol, 19-hydroxycholesterol, 7-ketocholesterol, cholesterol-alpha epoxide, cholesterol-beta-epoxide and an unidentified fraction. All these fractions except the unidentified fraction increased on cooking. On refrigerated and even on frozen storage all these fractions increased except the unidentified fraction, which showed a concomitant reduction. The changes in broiled meat were more pronounced compared to pressure-cooked meat. Results clearly indicated that even frozen storage of cooked meat did not prevent the development of cholesterol oxidation products. PMID- 22060575 TI - Effects of modified gas atmosphere packaging on pork loin colour, display life and drip loss. AB - Boneless loins from both sides of 20 pig carcasses were divided into five sections each and assigned equally to five packaging treatments: 100 % CO(2); 50 % CO(2)/50 % N(2); 25 % CO(2)/ 75 % N(2); 25 % CO(2)/65 % N(2)/10 % O(2) and vacuum. Loin sections were packaged in bags of low O(2) permeability, then stored in darkness at 1 degrees C for up to 22 days. Retail chops were cut from the sections and displayed in oxygen-permeable film under light at 3 degrees C for 3 additional days. The O(2) concentrations in packages with nominally anoxic atmospheres were 0.1-0.4 %. Sections stored in 25 % CO(2)/65 % N(2)/10 % O(2) had more surface greying and greening, stronger off-odour and psychrotropic counts after storage were more than one log(10) higher compared to sections from the other four treatments. Displayed chops from sections stored in 25 % CO(2)/65 % N(2)/10 % O(2) also had greying/greening at an outer layer of the chops. Off odour of chops was most pronounced for treatments with 10 % O(2) and vacuum. Drip loss from loin sections was highest for those in 100 % CO(2) (4.2 %) and lowest for those in vacuum (3.2 %). In conclusion, storage in CO(2) or CO (2)N (2) atmospheres benefitted the overall shelf life of pork. PMID- 22060576 TI - Meat quality in pigs subjected to minimal preslaughter stress. AB - The experiment compared meat quality in carcasses from pigs subjected to the absolute minimum of stress preslaughter with that from carcasses of pigs subjected to simulated commercial handling. A total of 120 pigs (85 kg) were used. They were a commercial hybrid and were processed in six equal batches. The minimal stress group were slaughtered with as little stress as possible. The simulated commercial handling group were mixed and transported for 2hr (80 km) and lairaged for 30 min. Simulated commercial handling increased plasma cortisol, plasma lactate, CPK and beta-endorphin. Muscle temperature measured in the m. longissimus dorsi (LD) at 45 min increased as did the ultimate pH in the m. adductor (AD). Overall eating quality was not affected. There were batch affects on most variables. Males were leaner and produced meat that had greater abnormal fat odour, darker cooked colour, poorer pork flavour, lower overall acceptability and was tougher. PMID- 22060577 TI - Meat quality of cryptorchid lambs grazing either dryland or irrigated perennial pasture with some silage supplementation. AB - The meat quality of lambs grazed on perennial pasture (ryegrass Lolium perenne, cocksfoot, Dactylis glomerata and white clover Trifolium repens) was examined in three treatments; group 1 (S) lambs were grazed on dryland pasture for 30 days and then offered a supplement of pasture silage ad libitum until slaughter, 30 days later (n = 21). Lambs in group 2 (P) were grazed on dryland pasture throughout (n = 28) and those in group 3 (IP) on irrigated pasture (n = 28). Lambs in group IP had a significantly (p < 0.001) heavier pre-slaughter liveweight and hot carcass weight than lambs in the other two groups. There was no significant difference (p < 0.05) infatscore between groups or in GR when adjusted to a common carcass weight. For cold carcass weight (reduced sample) IP lambs were still significantly heavier than those from group P, but no different to those from group S (n = 15, 15 and 10, respectively). There was no significant difference between groups for measures of fatness or for m. longissimus thoracis et lumborum (LL) area when adjusted to a common carcass weight of 23.6 kg. There was a significant difference between (p < 0.001) treatments for pH, group P carcasses having higher pH values for the LL muscle, with no treatment effect on m. semimembranosus (SM) pH. Differences between groups for meat colour values (L (*), a (*), b (*)) showed no consistent trend and there was no significant difference (p > 0.05) between groups in tenderness of the LL and SM muscles as indicated by shear force values. Aroma of the loin meat from pasture-fed lambs (P) was considered significantly (p < 0.05) stronger than from lambs in groups S and IP (n = 6, all groups) and the flavour of samples from lambs in group P was significantly (p < 0.05) stronger than from lambs in group IP. Overall there was no significant (p < 0.05) difference in acceptability between groups. The results indicate that consumers would be unlikely to detect the differences identified by the panel and that pasture silage will not have an adverse effect on lamb eating quality. PMID- 22060578 TI - The effects of non-vacuum packaging systems on drip loss from chilled beef. AB - This study investigated drip loss in chilled beef (hot-boned m. longissimus lumborum (LL)) under conventional packaging systems, in which a vacuum is applied, and non-vacuum packaging systems. The use of vacuum during the packaging process (vacuum packaging, CO(2) atmosphere packaging) was associated with increased drip. Drip was lower in heat-shrunk vacuum packaging than in non-shrunk vacuum packaging. A slow vacuum onset had no effect on drip formation, or may have increased it. The extent of pressure reduction (vacuum; range 0-1 atm) did not significantly affect drip formation, although the standard vacuum pressure (0 atm) tended to cause more drip loss than higher pressures. The three non-vacuum anaerobic packaging systems tested were: flushed with carbon dioxide without the pressure being reduced below atmospheric (Flush), or the same system with no CO(2) flush but a proprietary oxygen absorber added (Scavenger), or a combination of both (Flush/Scavenger). Storage was at -1.5 degrees C for up to 20 weeks. The Flush and Flush/Scavenger systems had considerably lower drip loss than the CAP standard system (6.4%, 6.5%, and 9.1% respectively); the Scavenger system had the lowest drip loss (5.2%). Drip losses generally increased with storage period, irrespective of packaging system. All non-vacuum packaging systems except the Flush system had very low oxygen levels (<0.l% v v ). The Flush system had considerably higher levels of oxygen (0.9%) with associated browning of meat samples. All packaging systems gave a hygienic shelf-life of at least 16 weeks. At 16 weeks, microbial numbers were highest (5 * 10(6)) in the Scavenger system. The meat from all packaging systems was acceptable to taste panels even after 16 weeks of storage at -1.5 degrees C. There were no significant differences between any of the packaging systems for any of the sensory attributes tested. The packaging systems with the best all round performance were the Flush/Scavenger and the Scavenger systems, depending on the storage-life required. PMID- 22060579 TI - Tyramine degradation by micrococci during ripening of fermented sausage. AB - The ability of tyramine oxidase exhibiting strains of Micrococcus varians to degrade tyramine in vivo during sausage fermentation was investigated. Fermented sausage was produced with a tyramine forming strain of Lactobacillus curvatus which acquired a final tyramine concentration of 190ppm. The addition of either one of two strains of M. varians exhibiting a potential to oxidise tyramine decreased the amount of tyramine formed to 160 and 150ppm, respectively. No effect on growth of L. curvatus and pH development in the fermented sausage was observed when micrococci were present during a three weeks ripening period. Sausage fermentation was further carried out with a non-amine forming strain of L. sake and M. varians after addition of 100ppm tyramine to the raw material. The amount of tyramine in the end product was 60ppm, and during the first 10 days of ripening the decrease was faster on the outside of the sausage. PMID- 22060580 TI - Effect of comminution method and raw binder system in restructured beef. AB - The effect of particle size, method of particle size reduction (grinding, flaking, slicing) and alginate or Fibrimex(TM) binding systems on processing properties of restructured beef were investigated. The size of semimembranosus muscles was reduced with a meat slicer, grinder or flaker (Comitrol) through machine openings that were 2, 4 and 8 mm in size. Bind of meat pieces in raw and cooked beef steakettes were measured. Sensory evaluation to determine the effect of method of size reduction on texture of beef steakettes was done only on steakettes manufactured with alginate. Beef steakettes manufactured with the alginate binding system had significantly (p < 0.05) higher raw bind values than did the beef steakettes manufactured with Fibrimex. Slicing meat for the manufacture of restructured beef steakettes resulted in a higher raw bind than did either grinding or flaking the meat. Significant (p < 0.05) interactions were observed for the bind of cooked steakettes between binder and method of size reduction and binder and opening size. When alginates were used to make restructured steakettes the bind of the cooked product was less (p < 0.05) when meat was sliced than when it was ground or flaked. However, when Fibrimex was used, bind was stronger when sliced meat was used. The alginate system resulted in higher binds for cooked product when particle size was smaller but with the Fibrimex system bind was higher when particle sizes were larger. A consumer panel on alginate restructured steakettes showed no preference for the texture produced by the different methods of particle size reduction. PMID- 22060581 TI - Oxidative stability and dietary treatment with vitamin E, oleic acid and copper of fresh and cooked pork chops. AB - Research has been conducted on the effects of feed supplementation with vitamin E, oleic acid (sunflower oil) and copper on some quality characteristics of pork chops. The study was based on the measurement of pH 45' and 24 hr post mortem, proximate composition, colour both objective and sensory, colour stability after packing in oxygen permeable film and protective atmosphere, copper and iron contents, vitamin E content in fresh and cooked chops, peroxide and TBARS value in raw and cooked meat, total cholesterol, cholesterol oxides and aldehydes in cooked meat, sensory evaluation of the eating quality of cooked chops and iodine number of subcutaneous fat. Vitamin E content was significantly higher with oil and vitamin supplementation. No variation has been observed in copper and iron contents. A higher stability of the colour of meat packed under modified atmosphere has been observed with increasing vitamin E content, but the same did not apply with meat packed in oxygen permeable film. No differences have been observed on fatty acid oxidative stability of fresh m. longissimus dorsi and cooked chops (peroxide and TBARS values), on cholesterol oxidation and aldehydes production of cooked chops with increasing vitamin E content. Iodine number in supplemented animals reached levels normally considered at risk for fat firmness. PMID- 22060582 TI - The polyunsaturated fatty acid composition of beef and lamb liver. AB - The effect on liver fatty acids of two typical beef production systems, steers fed grass (grazing) and bulls fed concentrates, was investigated. Liver fatty acids were also studied in lambs grazing grass. Total fatty acid content of liver in the beef animals was not affected by production system, being 3.5% for grass and 3.7% for concentrates although carcasses of the latter animals were leaner. The percentages of the major non polyunsaturated fatty acids (PUFA) were also similar: (concentrates in parentheses) 18:0, 25.2% (25.1%); 16:0, 13.3% (14.5%); 18:1 12.6% (14.0%). Total liver PUFA contents were similar for the two production systems and much higher than in muscle from the same animals. All n-3 PUFA were present in greater amounts in liver from grass fed animals and n-6 PUFA were higher in concentrate fed animals: mg/100g liver, 18:3n-3 92 (32); 20:5 n-3, 151 (17); 22:5 n-3, 283 (108); 22:6 n-3, 83 (32); 18:2 n-6, 172 (444); 20:4 n-6, 194 (270). The P:S ratios were 0.20 (grass) and 0.32 (concentrates) and the n-6:n-3 ratios were 0.71 and 4.8, respectively. Livers from grass-fed lamb had a higher fat content, 4.9%, than the beef livers and a lower percentage of 18:0, (21%); but more 16:0, (16%) and 18:1 (21 %). Total PUFA content of lamb's liver resembled that of beef liver and the composition was similar to that of the steers fed grass. However the concentrations of 18:3 n-3 and 22:6 n-3 were higher in lamb and contributed to a lower n-6: n-3 ratio of 0.46 although the P:S ratio of 0.18 was similar to that in beef liver. Ruminant liver is potentially a good source of C20 and C22 PUFA in the human diet particularly from grass fed animals, with a highly desirable n-6:n-3 ratio and this may be more important nutritionally than the low P:S ratio since people can offset this elsewhere in the diet. PMID- 22060583 TI - Fatty acid content and composition of UK beef and lamb muscle in relation to production system and implications for human nutrition. AB - Although ruminant meats normally have a low ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids (P:S ratio), the muscle contains a range of C(20) and C(22) PUFA of both the n-6 and n-3 series of potential significance in human nutrition. However, information on the amounts of these fatty acids in muscle and how they are modified by production system is limited In this study, the content and composition of fatty acids was determined in several muscles from beef steers fed grass (grazed) and bulls fed cereal concentrates. These are the two main types of beef production in the UK and Europe. Muscle fatty acids were also determined in lambs fed grass (grazed on pasture). The total fatty acid content of all muscles studied was less than 35 g kg(-1). The percentages in total fatty acids of all n-3 PUFA were higher in muscles from steers fed grass than from bulls fed concentrates whereas all n-6 PUFA were higher in the latter. The gluteobiceps muscle contained the largest amounts of fatty acids including PUFA and the m. longissimus dorsi the least amounts of PUFA in beef and lamb, and m. longissimus contained the lowest percentages of PUFA. Arachidonic acid was the major fatty acid in the C(20) + C(22) PUFA in beef from both production systems with twice as much in muscles from bulls fed concentrates. The P:S ratios were higher in the latter animals, range 0.21-0.34 compared with 0.08-0.13 in the steers fed grass. However, the n6:n-3 ratio was much less desirable in the bulls, 15.6-20.1 compared with 2.0-2.3 in the steers fed grass. These effects of production system in ruminants are larger than previously reported. Lamb muscle P:S ratios resembled those in grass-fed beef but the n-6:n-3 ratios were lower. The percentage of trans unsaturated 18:1 fatty acids was similar in both cattle production systems but lamb muscles contained twice as much as beef. Although the concentrations of the C(20) and C(22) PUFA are much lower than in fish, maintaining high n-3 levels in ruminant meats through grass feeding may be advantageous in human nutrition since meat is more widely consumed. PMID- 22060584 TI - Changes in lactic acid levels during thawing of lamb chops. AB - Loins from 20 lambs with an ultimate pH ranging from 5.5 to 6.4 were frozen and stored at -20 degrees C, then thawed at + 3 degrees C. During thawing, muscle (m. longissimus lumborum) lactate was measured in samples taken when the meat temperature reached -20, -5, -2, 0, and + 2 degrees C. At -5 degrees C, muscle lactate concentration was similar to that at -20 degrees C, but at -2 degrees C lactate levels were double those at -20 degrees C. As the temperature increased to +2 degrees C lactate concentrations fell from their -2 degrees C level. Low pH (5.5-5.6) and intermediate pH (5.7-6.1) meat at +2 degrees C had a higher lactate level than at -20 degrees C, with the greatest difference occurring in the low pH group (5 mmol lactate kg equating to approximately 0.05 pH unit increase). High pH meat (6.2-6.3) had similar lactate levels at -20 degrees C and +2 degrees C. These results demonstrate the importance of measuring the pH of frozen meat immediately rather than thawing the meat before measurement, and also show that meat pH may change on thawing, depending on the ultimate pH of the sample. PMID- 22060585 TI - A reporter protein for meat integrity. AB - A method for distinguishing fresh from thawed frozen samples of porcine and bovine meat is proposed.Crude soluble extracts from fresh (stored at +4 degrees C for 0-3 days) or deep frozen (at -80 degrees C) meat samples from pork and beef, were assayed by blocking ELISA to estimate m-MDH (mitochondrial malate dehydrogenase) titres. As a rule, a separate aliquot of each test sample was placed at -20 degrees C until frozen and subsequently thawed for the preparation of the extract whose analysis gave the 'self reference' m-MDH titre. For a given meat sample calculation of the tau index, 'tau', was proposed as the ratio between the self reference value and the original m-MDH titre. The 95% tolerance for tau for fresh and thawed meat, suggests that the method is suitable for this kind of analysis. PMID- 22060586 TI - Letter to the editor. PMID- 22060587 TI - Letter to the editor: Initial toughness of meat-The response. PMID- 22060588 TI - Lipid characteristics associated with oxidative and glycolytic fibres in rabbit muscles. AB - The purpose of this study was to specify the intramuscular lipid characteristics which are related to the metabolic type of muscles. Two glycolytic muscles (Longissimus lumborum and Psoas major), two oxidative ones (Soleus and Semimembranosus propriosus) and an intermediate one (Gastrocnemius laterale) were dissected from rabbit carcasses. The results showed that: PMID- 22060589 TI - Influence of partial replacement of NaCl with KCl on lipid fraction of dry fermented sausages inoculated with a mixture of Lactobacillus plantarum and Staphylococcus carnosus. AB - The effect of partial replacement of NaCl (3% NaCl) with KCl (1.5% NaCl and 1% KCl) on the lipid fraction of dry fermented sausages inoculated with Lactobacillus plantarum and Staphylococcus carnosus as starter culture was analysed. The reduction in salt concentration did not affect the Micrococcaceae count. A positive effect on the intensity of lipolytic activity was observed as a consequence of the decrease in salt level. There was no decrease in the oxidative processes. The higher amounts of volatile fatty acids found suggest that the tested modification enhances some of their mechanisms of synthesis. PMID- 22060590 TI - Lipolysis in a Belgian sausage: Relative importance of endogenous and bacterial enzymes. AB - The importance of bacterial and meat enzymes in lipolysis and carbonyl formation was evaluated during dry sausage ripening. Sausages were prepared with and without addition of an antibiotic-antimicotic mixture. In some experiments, an extra inoculum of Micrococcaceae was added and in two experiments, glucose was omitted. Total viable bacterial counts after 21 days were lowered by at least 2 log units in the presence of antibiotics. Free fatty acid productions after 3 and 21 days, in the presence of antibiotics were not significantly lower than observed in the control sausages. Total carbonyl compounds (benzidine reaction compounds) were significantly lowered by the presence of antibiotics compared to the control sausages except when glucose was omitted from the recipe. The data suggest that lipolysis is almost exclusively brought about by muscle and fat tissue. Polyunsaturated fatty acids are liberated from the polar lipid fraction and their specific liberation is higher than for monounsaturated and saturated fatty acids. Carbonyl production from lipids seems to be independent of bacterial activity. PMID- 22060591 TI - On-line, proximate analysis of ground beef directly at a meat grinder outlet. AB - The fat, moisture and protein contents of ground beef were determined on-line by a diffuse reflectance near infrared (NIR) spectroscopy instrument at the outlet of a meat grinder. Beef samples in the range of 6.2-21.7% fat, 59.6-72.9% moisture and 18.1-20.7% protein were studied. Calibrations from samples ground with hole diameters of 4, 8, 13 or 19 mm in the grinder plate were validated. In addition, calibrations of combinations of these samples from the different hole diameters were validated. Prediction errors, expressed as root mean square error of cross validation of the beef samples, were 0.73-1.50% for fat, 0.75-1.33% for moisture and 0.23-0.32% for protein, depending on the hole diameter of the grinder plate. Calibrations from samples ground with the smallest hole diameters gave lowest prediction errors. The present prediction error results are only slightly higher compared to reported prediction error results using conventional at- and off-line NIR instruments. It is concluded that the on-line NIR prediction results were acceptable for samples ground with grinder plates of 4, 8 or 13 mm hole diameter. PMID- 22060592 TI - Staphylococcal growth and enterotoxin production in the presence of meat cultures (non LAB). AB - The effect of meat cultures (non lactic acid bacteria) on the growth and production of enterotoxins and thermonuclease by Staphylococcus aureus was studied. Micrococcus varians did not affect growth nor the synthesis of metabolites. Levels of enterotoxins A, B and D produced by the respective S. aureus strains were reduced by S. xylosus, S. saprophyticus and S. carnosus. The two latter species prevented production of enterotoxin C(1) and S. xylosus markedly reduced the amount produced. The three coagulase-negative staphylococci showed little inhibitory effect on the growth of S. aureus. Penicillium nalgiovense did not show inhibitory activity against the four S. aureus strains. Debaryomyces hansenii slightly inhibited growth of the enterotoxin A-producing strain, but reduced enterotoxin synthesis at 30 degrees C. Thermonuclease was detected whenever enterotoxins were detected though the influence of the effector organism was dependent on the test strain. PMID- 22060593 TI - Utilization of image processing to quantitate surface metmyoglobin on fresh beef. AB - Ground beef patties were manufactured with various combinations of ascorbic acid and mechanically recovered neck bone lean (MRNL) to study the use of image processing in predicting percentage surface metmyoglobin (metMb) on fresh beef. Ascorbic acid and MRNL cause various color phenomena that resulted in a wide range of variation in surface color. Patties were also stored over six days of retail display to cause further color changes. Surface color was assessed by several different accepted methods. A prediction equation for percentage surface metMb included mean values for hue, saturation and intensity. Root mean square error, R-square and Mallow's Cp statistic were used as selection criteria for choosing the best predictive model. Image processing hue, saturation and intensity accounted for 93% of the variation in percentage surface metMb. Since hue, saturation and intensity each contribute to overall color profile it is logical that these parameters are good predictors. These data indicate that image processing is capable of objectively measuring percentage surface metMb. PMID- 22060594 TI - Parma ham: Correlation between myotypological parameters of Biceps femoris muscle and qualitative characteristics of fresh and seasoned product. AB - The morphofunctional characterisation of the Biceps femoris muscle was studied in 128 pigs intended for use as Parma ham, as a means of evaluating the raw material in relation to its transformation into a seasoned product answering to the requirements of its trademark. Organoleptic tests were carried out on both fresh and seasoned product, and the seasoned product was chemically characterised. The following defects in fresh hams-muscle which was pale in colour and of unsatisfactory firmness, insufficent compactness, poor thickness of fat cover layer-were found to be strongly correlated to the increase in white fibres of the IIa type; no links were found, however, between the measurement of myofibre diameters and these defects. Principal component analysis, applied to the complete set of histoenzymatic and organoleptic variables considered, reveals the qualitative characteristics of seasoned ham as having no close correlation with the histoenzymatic parameters of the fresh product; the authors nevertheless hope that myotypological examination will become one of the parameters in the evaluation of meat quality. PMID- 22060595 TI - Comparison between two statistical models for prediction of turkey breast meat colour. AB - The aims of the present study were: (1) to determine the relevant objective measurements which could express visual assessment of turkey meat colour; and (2) to use these variables for the early prediction of the colour development of turkey breast meat. The colour of the meat was assessed subjectively by an expert at a processing plant at 24 hr post mortem, using a four-category scale (score a: light-pale meat, score b: light pink meat or normal meat, score c: dark meat, score d: very dark meat). Objective measurements included meat pH, temperature, dielectric loss factor, pigment concentration, L(*) (lightness), a(*) (redness) and b(*) (yellowness) colour coordinates determined at different times post mortem. Colour coordinates and pH were chosen as relevant variables when measured at 1 and 4 hr post mortem and were used in prediction models. Linear analysis (canonical discriminant analysis) showed that the efficiency of prediction was 15%. A non-linear analysis (neural network) gave better prediction; the colour of the meat being correctly predicted for 70% of the muscles. PMID- 22060596 TI - Effects of dietary alpha-linolenic acid on the fatty acid composition, storage stability and sensory characteristics of pork loin. AB - Effects of dietary alpha-linolenic acid on the fatty acid composition, storage stability and sensory characteristics of cooked pork were studied. Dietary alpha linolenic acid (LNA) significantly (p < 0.05) increased the proportion of n-3 fatty acids and the degree of unsaturation in the neutral lipids and phospholipids. The increases in n-3 fatty acids were observed in the total lipids, triglycerides, phosphatidylethanolamine and phosphatidylcholine, and mainly consisted of C18:3n3, C20:5n3 and/or C22:5n3. The thiobarbituric acid reactive substances (TBARS) values (mg malondialdehyde per kg meat) of cooked vacuum packaged loins remained below 1.5, but in loose packaged loins TBARS values increased more than 3 times those of 0 time values during 2-day storage at 4 degrees C. The TBARS values of loins after LNA-enrichment were significantly higher than those of the control in both vacuum and loose packaging, and the increase of unsaturation in fatty acids had a strong prooxidant effect. The increase in dietary LNA enrichment increased oxidation (TBARS values) and had a detrimental effect on the acceptability of cooked pork loins held for 2 days in loose packaging. PMID- 22060597 TI - Changes in volatile compounds of Parma ham during maturation. AB - Changes in the aromatic profile of Parma ham caused by the normal course of aging up to 12 months were examined in order to identify distinctive signals for different maturing periods (6, 9, 12 months). The 28 samples analysed, divided among the three periods mentioned above, provided an aromatic profile in which methyl esters were the most relevant signals, followed by carbonyl compounds and alcohols. The greatest discriminating power is to be ascribed to components such as 3-methylbutanal and ethyl esters, and alcohols like 1-propanol, 1-butoxy-2 propanol and 2-butanol. These compounds were present in higher percentages at 12 months of aging. PMID- 22060598 TI - Calpains from thaw rigor muscle. AB - Pre-rigor beef M. Longissimus lumborum and diaphragma were frozen at -70 degrees C and thawed at different temperatures and the activities of extracted calpains and the toughness of heated meat compared with those in chilled muscle. Fresh muscle contained about 14 MUg of MU-calpain/g and was unaffected by freezing, but was reduced after thawing. Rapid thawing at 30 degrees C for 20 min reduced the MU-calpain to 14%. When cooked from the frozen state, extensive shortening occurred and tender meat was obtained. By storing at -3 degrees C for 1 day, thaw-shortening was prevented, but tougher meat obtained. The MU-calpain decreased to 70% whilst the m-calpain was unaffected. Toughness decreased after further storage at -3 degrees C, as did the MU-calpain. The latter changes were similar to those during development of rigor mortis and ageing of non-shortened meat stored at 4 degrees C. Variation in calpain activity, rather than in sarcomere length, are likely to be the cause of toughness variation in thaw rigor muscle. PMID- 22060599 TI - Predicting variability of ageing and toughness in beef M. Longissimus lumborum et thoracis. AB - The object of this study was to determine muscle characteristics which might predict meat toughness. Eleven Charolais cattle were slaughtered at approximately 26 months of age and the Longissimus lumborum et thoracis muscle was taken 1 hr post mortem and stored at 12 degrees C for 24 hr and then at 4 degrees C. The average half-life for ageing in these raw muscles was 4.6 days but the toughness varied widely between the animals. Toughness varied 3-fold and the rate of ageing varied 20-fold between animals. Correlations were done to determine which characteristics might explain this variability. Toughness was correlated positively with increase in oxidative status of muscle and the initial levels of calpastatin. Toughness was correlated negatively with the initial levels of MU- and m-calpains and cysteine and serine proteinase inhibitors, the initial pH values and the rates of their decline. The rates of ageing were highly correlated positively with the initial levels of proteinase inhibitors and the rates of decline of calpastatin and negatively with the ultimate amounts of expressible juice. There was a wide variability in tenderness in M. Longissimus lumborum et thoracis from similar animals. Variations in metabolism and enzyme activity controlled by inhibitors and calpains appear to be largely responsible for this variability. PMID- 22060600 TI - Changes affecting the Longissimus dorsi, Triceps brachii caput longum and Rectus femoris muscles of young Friesian bulls during meat ageing. AB - The chemical composition and post-mortem changes during 3-14 days of ageing were studied on three muscles (Longissiums dorsi, Triceps brachii caput longum, Rectus femoris) from 13 young Friesian bulls. Chemical composition varied widely between animals (p < 0.001) and muscles (p < 0.001), and did not change during post mortem storage. Significant changes affecting the non-protein nitrogen and soluble protein nitrogen contents were similar in all three muscles but differed from animal to animal. The increase in non-protein nitrogen can be considered as an indicator of proteolysis. Proteolysis extended to 14 days post mortem. The myofibril fragmentation index increased significantly (p < 0.001) between 3 and 7 days post mortem along the same pattern, irrespective of the muscle and animal. A ceiling was reached at around 7 days post mortem, by which time maximum breakdown of the structure had probably occurred. No significant relationship was observed between chemical composition, changes in the soluble protein nitrogen, breakdown of structures and carcass characteristics. PMID- 22060601 TI - Establishment of provisional quality assurance guidelines for assessing the hygienic adequacy of beef side cooling regimes. AB - The hygienic adequacy of beef side cooling regimes can be assessed from temperature histories obtained for a site within the aitch-bone pocket. Each temperature history is used to generate a numerical value, the Process Hygiene Index (PHI), which reflects the amount of mesophilic pathogen growth that the cooling regime allows. The PHI concept is proposed as a quality assurance tool for assessing beef side cooling. To develop provisional PHI guidelines for acceptable cooling, a chilling regime for carcasses which would yield frozen, boxed products was monitored on each of 11 days. Although the regime was hygienically acceptable, it was marginal in that cooling some sides to 7 degrees C took almost the permitted maximum time of 48 hr. The guidelines, derived from that process, based on a conventional three-class sampling plan, where the maximum acceptable value (M) is the highest PHI value obtained and the target value (m) is the 80th percentile PHI value of the pooled data from all acceptable, monitored trials. The proportion (c) of sample values that may lie between (m) and (M) was determined from the batch that had the highest PHI values. The proposed guidelines for the hygienically acceptable cooling of beef sides destined for fabrication to frozen product are: M = 19; m = 14; and c = 60 %, with no fewer than five samples being tested per batch (n >= 5). For sides destined for chilled products, a processor may wish to use more stringent, in house guidelines, to assure an extended product storage life. PMID- 22060602 TI - An ultrastructural observation on charquis, salted and intermediate moisture meat products. AB - Charqui meats are tropical intermediate moisture meat products containing 45% moisture and 15% salt with an A(w) of 0.70-0.75. Light microscopic studies of a charqui derivative popularly known as Jerked beef (JB) demonstrated considerable shrinking of muscle cells and the formation of fluid channels. The area occupied by muscle cells in JB was diminished by 30-40% in comparison with control samples. At the ultrastructural level, A-bands including the M-line disappeared indicating proteins were lost during processing. Z-lines appeared to be fragmented. In the enlarged extracellular spaces, collagen fibers retained their banding patterns although an empty space was observed surrounding these fibers. The denaturation of myofibrillar proteins during processing and the osmotic pressure caused by salting create conditions for water movement from the myofibrillar compartments to the intermyofibrillar space, then to the extracellular matrix and ultimately to the meat surface. PMID- 22060604 TI - Halothane genotype and pork quality. 1. Carcass and meat quality characteristics of three halothane genotypes. AB - The carcass and meat quality characteristics of three halothane genotypes in pigs were evaluated. Sixty crossbred Landrace*Large White pigs (NN=25, Nn=19, nn=16) of +/-86 kg live weight were slaughtered, the carcasses chilled for 24 h at 2 degrees C, certain carcass and meat quality traits determined and the shoulder and leg cuts deboned and cut into primal cuts. Dressing percentage of the Nn pigs was higher (P<0.05) than that of the NN and nn pigs. Carcass length was the longest (P<0.05) for the nn pigs. Midline fat measurements as well as measurements at the 2nd-3rd last rib (45 mm from the midline) indicated that the nn pigs had less fat (P<0.05) and a larger eye muscle width (P<0.05), depth (P<0.001) and area (P<0.001) than the NN or Nn pigs. This resulted in the nn pigs having the highest (P<0.05) percentage predicted carcass lean content. Fat, bone and lean yield of the shoulder identified the nn pigs with the least bone (P<0.05) and fat (P<0.001) and the highest lean yield (P<0.05), expressed as a percentage of total shoulder weight. Yield from the legs identified the nn pigs as having the lowest fat (P<0.001) and highest lean (P<0.05), expressed as a percentage of total leg weight. The primal lean cuts (topside, silverside, thickflank and rump) from the legs showed that the nn pigs had the highest values (P<0.05) for lean as a fraction of cold carcass weight. This resulted from the higher weight of these cuts (P<0.05) in the nn pigs. Calculation of bone yield in the legs showed that the femur weights were highest (P<0.05) for the Nn pigs, also when expressed as percentage of leg weight (P<0.05) and as a fraction of cold carcass weight (P<0.05). Comparison of meat quality traits show that the nn pigs had poor quality with regard to pH(45) (P<0.001), pH(24) (P<0.05), drip loss (P<0.001) and reflectance values (P<0.05). PMID- 22060605 TI - Halothane genotype and pork quality. 2. Cured meat products of three halothane genotypes. AB - The effect of the halothane gene on cured meat products was investigated using the meat from 60 Landrace*Large White pigs of known halothane genotype (NN=25, Nn=19, nn=16). The backs and hams were used to prepare cured, smoked bacon and canned hams. Initial bacon gain in pumped weight was significantly higher (P<0.001) for the NN (15.2%) and Nn (14.9%) compared to the nn pigs (8.9%). Similarly, the total gain in bacon yield was the highest for the Nn (11.5%) and NN pigs (10.0%), and significantly higher (P<0.05) than the bacon from nn pigs (3.4%). Differences between sexes were not significant. Canned hams (no phosphate) from the NN genotype had a significantly (P<0.001) lower percentage cooking loss (27.9%) compared to the Nn (30.1%) and nn pigs (31.1%), which did not differ statistically. Although addition of phosphates (0.3% on final product) led to a decrease in percentage cooking loss, the genotypes gave a similar response, with the NN genotype having 13.8% cooking loss, significantly lower (P<0.001) than the Nn (16.9%) and nn genotypes (17.7%). The results indicate reduced product quality with the inclusion of the halothane gene. PMID- 22060606 TI - Halothane genotype and pork quality. 3. Comminuted meat products derived from the three halothane genotypes. AB - The effect of the halothane gene on cured meat products was investigated using the meat from 60 Landrace*Large White pigs of known halothane genotype (NN=25, Nn=19, nn=16). Results for the two types of fresh sausage manufactured (with and without rusk) indicated that the NN pigs (15.7%) had lower total moisture losses (P<0.05) compared to the nn pigs (18.9%), with Nn being intermediate (17.4%) for the sausage without rusk. Where rusk was added, there were no significant differences between genotypes for moisture losses (NN=12.6%, Nn=13. 0%, nn=14.2%). Taste panel evaluations of the fresh sausages made without rusk indicated no genotypic influence for juiciness, however the sausage made with the rusk was judged the juiciest for the nn genotype, with Nn being intermediate and NN the least juiciest. The smoking and cooking losses during manufacturing of the emulsion product (vienna) indicated that the nn genotype (12.5%) had significantly (P<0.05) higher total losses than the Nn genotype (11. 3%), with NN being intermediate (12.4%). PMID- 22060607 TI - Effects of dietary high-oleic acid sunflower oil, copper and vitamin E levels on the fatty acid composition and the quality of dry cured Parma ham. AB - The effects of seven isoenergetic dietary treatments: (1) no sunflower oil, 35 mg/kg Cu, without alpha-tocopheryl-acetate added; (2) to (7) 6% high oleic acid sunflower oil (HOSO), 35 or 175 mg/kg Cu crossed with a 0, 100 or 200 mg/kg alpha tocopherol addition, were tested on quality characteristics of dry cured Parma hams from a total 84 Large White gilts. No statistically significant effect was detected on parameters of early evaluation of seasoning loss of hams. The seasoning loss and intramuscular fat content of seasoned hams averaged 28.1 and 3.3%, respectively, with no effect of the diet composition. The CIE L*a*b* colour values taken on the surface of the lean from Parma ham were not affected by dietary oil inclusion, nor by copper levels and by alpha-tocopherol addition in the feed mixture, except for the 'a' value that increased in HOSO groups (P<0.01) and in groups with alpha-tocopherol addition (P<0.01). The TBARS values in lean were reduced by the inclusion of HOSO (P<0.05) and alpha-tocopherol supplementation (P<0.10). Compared to the no oil group, the Parma hams in the HOSO groups showed a higher oleic acid content in the covering fat, but not different in neutral and polar fractions from semimenbranosus muscle. The oil inclusion reduced the saturated fatty acid content in subcutaneous fat and neutral lipids fraction from muscle to 30-34% No effect of alpha-tocopherol and copper levels were observed on fatty acids profiles. From the subjects fed the HOSO diet softer Parma hams were produced than those fed the control diet (chi(2)<0.05), while alpha-tocopherol and Cu levels did not influence the sensorial evaluation of hams. The inclusion of an oleic acid rich source in heavy pig diet brought about an improved nutritional value, but also the possible need of a prolonged ageing time to achieve an ideal firmness of Parma ham. Dietary alpha-tocopherol supplementation improved the red colour slightly and the lipid stability in Parma ham, while the supplementation of Cu in the diet had no influence on the tested parameters. PMID- 22060608 TI - Lipolysis in muscles during refrigerated storage as related to the metabolic type of the fibres in the rabbit. AB - The relation between lipolysis and the metabolic fibre type was investigated during refrigerated storage of rabbit muscles. Free fatty acid, monoacylglycerol and diacylglycerol contents and free fatty acid composition were compared in five muscles immediately after slaughter and after a 7-day-storage at 4 degrees C. The results showed that. (1) The amount of free fatty acids sharply increased during the refrigerated storage (from 2-10 to 11-32 mg/100 g of muscle), especially that of long chain polyunsaturated fatty acids (from less than 0.1 to 1.4-3.3 mg/100 g of muscle). (2) The glycolytic muscles contained 1.5 times less free fatty acids than the oxidative ones. However, the rates of phospholipid and triacylglycerol hydrolysis were not related to the metabolic type of the fibres. (3) The contribution of phospholipids to free fatty acid fraction was twice that of triacylglycerols in the glycolytic muscles whereas it was similar or lower to that of triacylglycerols in the oxidative muscles. PMID- 22060609 TI - Combined use of Pronase E and a fungal extract (Penicillium aurantiogriseum) to potentiate the sensory characteristics of dry fermented sausages. AB - A combination of an extract of Penicillium aurantiogriseum and Pronase E was used in an attempt to enhance the sensory characteristics of dry fermented sausages, specifically, a salami-like one named "salchichon". The addition of Pronase E alone (600 units/kg) produced a rise in free amino acids and biogenic amines and also an increase in the ammonia content. Addition of the protease and fungal extract (100.87 mg protein/kg of mixture) brought about a decrease in the level of free amino acids and a larger increase in the ammonia content than the batch added with only Pronase E. There was also an increase in the amount of specific volatile compounds such as 2- and 3-methylbutanal, 2- and 3-methylpropanal and 2- and 3-methyl-1-butanol produced by the breakdown of amino acids in these fermented sausages. Values of pH, a(w) and dry matter were not affected by addition of the protease or fungal extract. In contrast, addition of Pronase E produced a notable change in the textural characteristics, reducing the hardness, cohesiveness, gumminess, chewiness and cutting force. Sensory analysis showed that fermented sausages manufactured with Pronase E and Penicillium aurantiogriseum extract had better odour, flavour, texture and, as a consequence, better general acceptability. PMID- 22060610 TI - Boar taint in pigs selected for components of efficient lean growth rate. AB - Genetic and nutritional effects on the boar taint traits of androstenone, skatole and indole and the eating quality traits associated with boar taint were examined by testing animals from four selection lines and a control line on isoenergetic diets, which differed in ileal digestible lysine: digestible energy (0.40, 0.76 and 1.12 g lysine/MJ DE). The selected lines resulted from seven generations of selection for high daily food intake, lean food conversion ratio (LFC) and lean growth rate on ad libitum (LGA) or restricted (LGS) feeding regimes in a Large White population. During performance test, from 30 to 90 kg, boars were fed on either ad libitum or restricted (0.75 g/g ad libitum daily food intake) feeding regimes. A sensory panel assessed heated fat samples for androstenone odour, skatole odour and abnormal odour. There were no significant differences between the selection and control lines or diets for log transformed fat content of androstenone, skatole, indole. The significant diet with feeding regime interaction for log transformed fat content of skatole and indole were essentially due to significantly higher log transformed fat contents with ad libitum feeding of the high lysine diet compared to restricted feeding (skatole: 1.94 vs -3.06, s.e.d. 0.43; indole: -3.44 vs -4.22, s.e.d. 0.28), as differences between feeding regimes on diets A and C were not significantly different from zero. There were no significant differences between selection and control lines for sensory panel score for abnormal odour or androstenone odour, but the LFC and LGA selection lines had a significantly higher skatole odour score than the LGS selection line. Neither diet nor feeding regime had any significant effect on sensory panel assessment of odour. Log transformed fat content of androstenone and skatole were significantly correlated with sensory panel score for skatole odour (0.37 and 0.46, s.e. 0.12), but not with sensory panel score for androstenone odour (0.06 and 0.09), such that they would not be useful predictors of androstenone odour. PMID- 22060611 TI - The relative effect of dietary energy density on repleted and resting muscle glycogen concentrations. AB - The aim of this study was to assess the effect of dietary energy density on the glycogen concentration of bovine gluteus medius (GM) and longissimus thoracis et lumborum (LTL) muscles in castrated and intact males. Cattle received diet C (90% whole corn and supplement: 10% alfalfa haylage) or diet AH (100% alfalfa haylage) in three experiments involving a 2*2 factorial cross-over design. Cattle fed an AH diet for 70 days prior to the first experiment had high glycogen concentrations in the GM (129+/-9.9 mmol/kg) and LTL (108+/-7.6 mmol/kg) at the first biopsy session. These concentrations are similar to GM (133+/-6.2 mmol/kg) and LTL (105+/-5.8 mmol/kg) glycogen concentrations when these cattle subsequently received diet C for 30 or 37 days. Diet C increased muscle glycogen concentration, but the consistency of the increase in glycogen was dependent on the initial concentration. When the initial glycogen concentration was depleted to 50 MUmol/g with one subcutaneous injection of adrenaline, repleted glycogen concentration was higher for diet C than AH (P<0.01) in all comparisons involving GM and LTL muscles of both steers and bulls. For resting muscle glycogen, the GM of bulls was more sensitive to the effect of diet C than the bull LTL or either muscle in steers. Diet was not a major determinant of resting muscle glycogen concentration. The ultimate pHs of GM, LTL and semimembranosus (SM) were not affected by diet and residual glycogen was lower in LTL of bulls fed either diet than for LTL of steers fed AH. Diet and male status did not affect residual glycogen in GM or SM. PMID- 22060612 TI - Glycogen concentrations in bovine longissimus dorsi muscle. AB - The aim of this study was to assess the effect of location within bovine longissimus dorsi (thoracis et lumborum) muscle (LTL) when determining glycogen concentration. Six locations in Angus heifers were sampled post mortem (EXP-1) and eight locations in live Charolais crossbred steers were biopsied (EXP-2). In EXP-1, there was more glycogen in the animals' left LTL (64.1+/-1.6 mmol/kg) versus the right LTL (57.0+/-1.6 mmol/kg) (P<0.05). Locations along the cranial caudal axis within LTL did not differ in glycogen concentration. Results for EXP 2 did not confirm the sidedness effect. Instead, it showed that glycogen concentration was lower at the cranial sampling locations near the 10th rib (89+/ 2.5 mmol/kg) than at the middle (97+/-2.0 mmol/kg) or caudal locations (96+/-1.9 mmol/kg) (P<0.005). Taking lactate accumulation into account (glycolytic potential) rendered those differences insignificant. Nevertheless, the tendency remained clear. The potential for dilution of glycogen by intramuscular fat deposits is discussed. The results indicate that one needs to be cautious in performing repeated sampling on bovine LTL. PMID- 22060613 TI - Thermal gelation characteristics of breast and thigh muscles of spent hen and broiler and their surimi. AB - Spent hen (98 weeks) and broiler (12 weeks) breast and thigh muscles were minced (1 mm orifice diameter) and washed with 0.1% NaCl. A portion of both unwashed and washed mince was mixed with cryoprotectants (CP) at the rate of 4% sucrose, 4% sorbitol, and 0.2% Na-tripolyphosphate to produce surimi and kept frozen at -20 degrees C. The mince and surimi were ground with 3% NaCl and a small amount of water to adjust the final moisture content of 80%. The pastes were stuffed into the sausage casing and heated at 90 degrees C for 15 min to produce gel. The effects of washing, heating and CP on colour composition and thermal gelation properties of hen and broiler minces and surimi were compared. Broiler mince was lighter and less red in colour, higher in protein and lower in moisture, lipid and collagen. Gel strength and breaking strength were higher in spent hen surimi compared to broiler surimi under similar gelation conditions. Gel elasticity, springiness and water retention properties were almost identical in two surimi. Gel quality was markedly deteriorated in spent hen surimi but not so in broiler surimi after 8 weeks frozen-storage. Although CP increased the gel strength of fresh surimi (non-frozen, 0 week storage) from both hen and broiler, they were more effective in broiler surimi than hen surimi in protecting the functional quality of gel. PMID- 22060614 TI - Influence of feeding intensity, grazing and finishing feeding on muscle fibre characteristics and meat colour of semitendinosus, longissimus dorsi and supraspinatus muscles of young bulls. AB - Forty-one autumn-born Friesian bull calves were allocated to two production systems (Extensive='E' and Intensive='I'). In the E-system, animals were loose housed and fed a roughage-based diet from October to May, followed by a grazing period from May to October. Ten animals were slaughtered directly from pasture (360 kg BW) and 11 after a 10-week finishing feeding in tie-stalls (460 kg). E bulls were compared with intensively fed tie-stall housed young bulls (I) slaughtered at comparable weights (360 kg, n=11 and 460 kg, n=9). Semitendinosus (ST), longissimus dorsi (LD), and supraspinatus (SU) muscles were analysed histochemically, and the meat analysed for colour and pigmentation. In LD and SU, Type I % was higher in E- compared with I-bulls (P<0.05-0.006). In ST and LD, Type IIA % was higher in E- compared with I-bulls (P<0.01-0.009). As a result, Type IIB % was lower in all three muscles in E- compared with I-bulls (P<0.05 0.001). In E- compared with I-bulls, Type IIA and IIB fibre areas were larger in ST (P<0.05-0.03) and capillarization was higher in both ST and LD (P<0.001). In all three muscles, the activity of citrate synthase was higher (P<0.07-0.001) and that of lactate dehydrogenase lower (P<0.003-0.001) in E- compared with I-bulls. E-bulls had lower glycogen content than I-bulls in ST and LD at 360 kg, but higher at 460 kg following finishing feeding (P<0.008-0.001). Meat colour (lightness) was darker (P<0.001) and pigmentation was higher (P<0.001) in ST and LD of E- compared with I-bulls, with no effects in SU. In conclusion, histochemically different muscles respond differently to changes in the production system, and differences between the extensive and the intensive production system were narrowed after the finishing feeding. PMID- 22060615 TI - Influence of feeding intensity, grazing and finishing feeding on meat and eating quality of young bulls and the relationship between muscle fibre characteristics, fibre fragmentation and meat tenderness. AB - Forty-one autumn-born Friesian bull calves were allocated to two production systems (Extensive='E'and Intensive='I'). In the E-system, animals were loose housed and fed a roughage-based diet from October to May, followed by a grazing period from May to October. Ten animals were slaughtered directly from pasture in October [360 kg body weight (BW)] and 11 after a 10-week finishing period in tie stalls (460 kg). The E-bulls were compared with intensively-fed tie-stall-housed young bulls (I) slaughtered at comparable weights (360 kg, n=11 and 460 kg, n=9). The myofibril fragmentation index (MFI) was measured 24 h post mortem in semitendinosus (ST), longissimus dorsi (LD), and supraspinatus (SU) muscles, and meat quality characteristics and sensory evaluation of LD were performed on aged meat. Intramuscular fat content was lower (P<0.001) in all three muscles of E- compared with I-bulls. MFI of ST and LD was lower in E-bulls compared with I bulls, but only at 360 kg. In contrast, MFI of SU was higher in E- compared with I-bulls at 360 kg. In E- compared with I-bulls, shear force value of ST was higher (P<0.003) at 360 kg, but not at 460 kg. Panel scores for tenderness, taste and juiciness were all lower (P<0.006 to 0.001) and remarks for off-flavour higher in E- compared with I-bulls, the effects being most pronounced at 360 kg. A 10-week finishing period improved all meat and eating quality characteristics of E-bulls. In LD, the correlation between MFI and tenderness was 0.79 (P<0.001), which indicates a potential of MFI as an early predictor of tenderness. PMID- 22060616 TI - Effect of inoculation of mesophilic lactic acid bacteria on microbial and sensory changes of minced goat meat during storage under vacuum and subsequent aerobic storage. AB - Minced goat meat inoculated with cell suspensions of Lactococcus lactis ssp lactis (Lc. lactis) or Lactobacillus plantarum was stored under vacuum in PETPE film at 4 degrees C and transferred to aerobic storage for 7 days in LDPE bags. During storage under vacuum, the lactic counts of the inoculated samples dropped followed by the development of spontaneous lactic flora. The pH of meat was lower in the treated samples than in the control. Towards the end of vacuum storage cell densities were lower than those in the control only for psychrotrophs in L. plantarum treatment and coliforms and staphylococcal counts in Lc. lactis treatment. There were increases in lactic counts in both treated and control samples during aerobic storage after previous vacuum storage of 18 days in trial 1 and 9 days in trial 2 with reductions in the counts of different bacterial groups and deterioration in colour of the treated samples compared with the control. When goat meat chunks were surface sanitized in alcohol and treated with lactic cell suspension and vacuum stored, there was development of acid and salty taste (acceptable) in the treated samples whereas the control showed a bland taste. PMID- 22060617 TI - Bio-physical characteristics of gastrointestinal mucosa of celiac patients: comparison with control subjects and effect of gluten free diet-. AB - BACKGROUND: Intestinal mucosa is leaky in celiac disease (CD), and this alteration may involve changes in hydrophobicity of the mucus surface barrier in addition to alteration of the epithelial barrier. The aims of our study were i) to compare duodenal hydrophobicity as an index of mucus barrier integrity in CD patients studied before (n = 38) and during gluten- free diet (GFD, n = 68), and in control subjects (n = 90), and ii) to check for regional differences of hydrophobicity in the gastro-intestinal tract. METHODS: Hydrophobicity was assessed by measurement of contact angle (CA) (Rame Hart 100/10 goniometer) generated by a drop of water placed on intestinal mucosal biopsies. RESULTS: CA (mean +/- SD) of distal duodenum was significantly lower in CD patients (56 degrees +/- 10 degrees )) than in control subjects (69 degrees +/- 9 degrees , p < 0.0001), and persisted abnormal in patients studied during gluten free diet (56 degrees +/- 9 degrees ; p < 0.005). CA was significantly higher (62 degrees +/- 9 degrees ) in histologically normal duodenal biopsies than in biopsies with Marsh 1-2 (58 degrees +/- 10 degrees ; p < 0.02) and Marsh 3 lesions (57 degrees +/- 10 degrees ; p < 0.02) in pooled results of all patients and controls studied. The order of hydrofobicity along the gastrointestinal tract in control subjects follows the pattern: gastric antrum > corpus > rectum > duodenum > oesophagus > ileum. CONCLUSIONS: We conclude that the hydrophobicity of duodenal mucous layer is reduced in CD patients, and that the resulting decreased capacity to repel luminal contents may contribute to the increased intestinal permeability of CD. This alteration mirrors the severity of the mucosal lesions and is not completely reverted by gluten-free diet. Intestinal hydrophobicity exhibits regional differences in the human intestinal tract. PMID- 22060618 TI - Antioxidants modulate molecular mobility, oxygen permeability, and microstructure in zein films. AB - The effect of octyl gallate and propyl gallate on the molecular mobility, oxygen permeability, and microstructure of zein/glycerol films was studied. Films were cast from 70% ethanol/water containing 20% (w/w) glycerol and different amounts of the antioxidants propyl gallate or octyl gallate. The oxygen permeability and local mobility of these films were measured using phosphorescence from the dispersed triplet probe erythrosin B. Although both antioxidants increased the local mobility of the zein matrix to about the same extent, octyl gallate and to a lesser extent propyl gallate dramatically increased the permeability of the film to oxygen. Atomic force microscopy imaging indicated that propyl gallate induced aggregation of zein complexes, which could lead to a more condensed film. These results indicate that the addition of specific functional ingredients, such as antioxidants, to edible films may significantly affect the physical properties and structure and, thus, functional properties in ways that influence their eventual use. PMID- 22060619 TI - Purification and properties of rabbit muscle proteasome, and its effect on myofibrillar structure. AB - This paper describes the purification and properties of a multicatalytic proteinase complex, proteasome, from rabbit skeletal muscle, and its effect on myofibrillar structure. The purified proteasome gave a single band on polyacrylamide gel electrophoresis under non-denaturing conditions and gave eight bands under denaturing conditions, indicating that this enzyme comprises multiple hetero-subunits with low molecular mass. The purified proteasome was not activated by ATP and ubiquitin, and was markedly inhibited by Z-Leu-Leu-Leu-H (aldehyde). These data indicate that the purified proteasome is not 26S, but 20S. The proteasome degraded synthetic peptides maximally at pH 8.0. Relative to pH 8.0, activities were gradually decreased with the lowering of pH, but the degree of decrease was substrate-dependent, and the activity at pH 5.0 still retained about 30~60% of the activity at pH 8.0, indicating the possibility that the proteasome is active in the muscle during conditioning. When the proteasome was heated at 60 degrees C for 20 min and treated in the presence of 0.005% SDS, the activity increased over 1.5 and 4.5 times, respectively. SDS remarkably increased the V(max) value of the enzyme at pH 8.0. The proteasome was also activated by high hydrostatic pressure up to 100~150 M Pa and gradually decreased at 200 MPa or higher. Electron microscopic observation revealed that obvious gaps between filamentous structure, the complete loss of M-line and partial loss of Z-line structure were caused by proteasome. PMID- 22060620 TI - Determination of mitochondrial cytochrome B gene sequence for red deer (Cervus elaphus) and the differentiation of closely related deer meats. AB - The cytochrome b gene sequence for red deer was determined using the Dye Terminator Cycle Sequencing method and used for identification of deer meat in meat and meat products. Red deer showed a similarity of 94.1, 84.0, 81.1, 85.5 and 85.6% to sika deer (Cervus nippon), bovine, pigs, sheep and goats, respectively. To differentiate the deer meat, oligonucleotide primers RD-1(5' TCATCGCAGCACTCGCTATAGTACACT-3'), RD-2(5'-ATCTCCAAGTAGGTCTGGTGCGAATAA-3') were designed for the region of the cytochrome b gene of red deer. The PCR amplified 194 bp fragments from red and sika deer, but no fragments from bovine, pig, chicken, sheep, goat, horse and rabbit DNA. Although cooking the meats reduced the PCR products, red deer could still be detected in meat heated at 120 degrees C. To discriminate between red and sika deer, these PCR products were digested by a restriction enzyme (EcoRI,BamHI,ScaI) and analyzed by 4% agorose gel electrophoresis. As a result, the red deer fragment was digested by EcoRI to 67/127 bp fragments but not by BamHI and ScaI. The sika deer fragment was digested to 48/146 bp and 49/145 bp fragments with the two other enzymes, and thus it is possible to differentiate between the two kinds of deer from the digestion pattern of restriction enzymes. PMID- 22060621 TI - Some characteristics of lactic acid bacteria present in commercial sucuk samples. AB - A total of 10 sucuk samples, obtained from Denizli, Turkey were analysed for some physical, chemical and microbiological characteristics. In addition, lactic acid bacteria (LAB) strains producing bacteriocin-like metabolites were isolated and identified. The production of some typical metabolites of the cultures isolated was investigated. At the end of the research, the average values of the pH, water and fat content were 5.1, and 37.2% and 30.5%, respectively. Microbiological analyses results were determined: average 8.34 log CFU/g TAMB, 8.91 log CFU/g LAB (at the MRS agar) and average 8.25 log CFU/g LAB (at the Elliker's lactic agar). The average counts of yeast-mould, coliform and Enterobacteriaceae were found to be 5.0 log CFU/g, 3.28 log CFU/g and 3.27 log CFU/g, respectively. In this study, counts of yeast-mould in the two samples, coliform counts in the five samples, and Enterobacteriaceae counts in the three samples were < 1.0 log CFU/g. A total of 6 of 100 LAB isolates obtained from the sucuk samples were found as a strain producing bacteriocin-like metabolites. These 6 strains were identified as follows; 3 strains Lactobacillus plantarum and 3 strains Pediococcus pentosaceus. According to the findings, these strains have the potential to be used as a sucuk starter culture. Additionally, acid and flavour compounds, other undesirable metabolite-producing activities of the strains, were determined in the model system. From these results it was concluded, after the determination of the toxicological properties, that the 4 strains of LAB identified (L. plantarum 13 P. pentosaceus 15 P. pentosaceus 74 and P. pentosaceus 75) would be useful as the starter and protective culture in the processing of the sucuk and similar fermented products. PMID- 22060622 TI - Non-destructive prediction of selected quality attributes of beef by near infrared reflectance spectroscopy between 750 and 1098 nm. AB - Heifers (n = 70) were slaughtered and hung conventionally in an industrial meat plant. Near infrared (NIR) spectroscopy was studied for its ability to predict selected meat quality attributes, i.e. Warner-Bratzler shear force (WBSF), sensory tenderness, texture, flavour and acceptability. Freshly cut steaks (2.5 cm thick) were taken from the longissimus dorsi (LD) muscle at 1, 2, 7 and 14 days post mortem for NIR analysis. Other samples (also 2.5 cm thick) were taken at 2, 7 and 14 days post mortem, vacuum-packaged in plastic bags and stored at 20 degrees C for WBSF measurement and sensory analysis. Heifers were slaughtered in two groups; between slaughterings, replacement of the spectrophotometer lamp and lamp assembly was necessitated by a bulb failure. Using principal component regression (PCR), correlation coefficients of 0.82 and 0.73 were obtained for the prediction of WBSF in sample sets 1 and 2, respectively. On merging both sample sets, this value was lowered slightly (r = 0.61). Correlation coefficients obtained for the prediction of tenderness, texture, flavour and acceptability were 0.67, 0.53, 0.51 and 0.46 respectively (set 1); 0.72, 0.71, 0.45 and 0.67 (set 2); 0.53, 0.54, 0.24 and 0.42 (combined sets). PMID- 22060623 TI - Protein molecular interactions involved in the formation of frankfurters: Effect of fat level and heating rate. AB - The effect of the heating rate (0.55, 1.10 and 1.90 degrees C/min) on the types of interactions and proteins involved in emulsifying and gelation processes of high-fat (23%) and low-fat (9%) frankfurters was evaluated by means of a selective soluble protein study and SDS electrophoresis. The selective soluble protein analysis showed that with both fat levels alike, the molecular associations involved in the formation of the gel/emulsion network were hydrophobic interactions and hydrogen bridges, which are equally involved in protein denaturation and aggregation. It also showed that oxidation of the sulphydryl groups could facilitate molecule aggregation. Non-disulphide covalent bonds also play an essential role in the properties of frankfurters. Electrophoresis analysis showed that myosin heavy chain (MHC) and actin (A) were involved in both emulsifying and gelation processes of low-fat and high-fat frankfurters. PMID- 22060624 TI - A repeat national survey of muscle pH values in commercial pig carcasses. AB - Measurements of pH values at 45 min post-slaughter (pH(1)) in m. longissimus were taken in a total of 5598 commercial bacon weight carcasses. pH values at 24 h post-slaughter (pH(2)) were taken on a further 5598 carcasses. The overall mean pH(1) was 6.39 with 15.1% of values less than 6.0. The overall mean pH(2) was 5.64, none of the values recorded were greater than 6.5. This survey shows a small increase over the 1983 study in the incidence of potentially Pale Soft and Exudative (PSE) carcasses. It found no evidence of a Dark, Firm and Dry (DFD) problem related to high ultimate pH. PMID- 22060625 TI - Effect of incorporation of dietary polyunsaturated fatty acids in pork backfat on the quality of salami. AB - The suitability of backfat high in polyunsaturated fatty acids (PUFA) for salami manufacture was assessed. Eighty pigs (barrows and gilts) were fed four diets, containing 21, 25, 28 and 28 g PUFA/kg feed, originating mainly from soybeans and/or soybean oil in the first three diets and from linseed in the fourth. Salami was prepared with backfat from these pigs, according to gender and dietary treatment. Samples were taken throughout the ripening. The taste panel rejected the two high PUFA (diet 3 and 4) levels; moreover fishy off-flavours were detected for dietary treatment four. Twenty-five grams PUFA/kg feed, corresponding with 23% PUFA in backfat or 15% PUFA in salami, results in acceptable taste, if linoleic acid is the predominant PUFA. However, all PUFA levels resulted in salamis too soft to be commercialized, as evidenced by a fatty film on the salami slicing machine. PMID- 22060626 TI - Reference methods for the assessment of physical characteristics of meat. AB - As a spin-off of an OECD Workshop on pork quality, held in Helsinki in 1992, a group of scientists with many years of experience in the field of meat quality assessment convened in February 1993 for the first time, and subsequently in 1994 and 1995, in Kulmbach at the German Federal Centre for Meat Research under the auspices of the OECD research project Management of Biological Resources. Three specific areas were discussed in order to develop internationally accepted reference methods: In the autumn of 1997 the methods were brought into their final form at the Meat Industry Research Institute of New Zealand (MIRINZ). They are presented in this paper. PMID- 22060627 TI - Diverse lamb genotypes-1. Yield of saleable cuts and meat in the carcass and the prediction of yield. AB - Carcass measurements and composition data were obtained for 591 lambs representing two sexes (307 cryptorchid males, 284 ewes). The lambs were sired by a selection of Texel (T), Poll Dorset (PD), Border Leicester (BL) and Merino (M) rams, crossed with Border Leicester * Merino (BLM) and Merino (M) ewes giving 6 genotypes (T * ELM, PD * BLM, T * M, PD * M, BL * M, M * M). m * M carcasses were significantly (p < 0.05) leaner than all other genotypes as measured by GR at a common weight, except for ewe carcasses where they were not significantly leaner than T * M carcasses. There was no difference in GR between Texel and Poll Dorset sired carcasses. The BL * M and PD * BLM carcasses were the fattest at the 5th rib. M * M lambs produced the lightest carcasses in each sex. Genotype differences were found for conformation using the EUROP scoring system. M*M lambs had a greater proportion (p < 0.001) of poorer scores particularly compared to PD * BLM and T * BLM carcasses. Analysis of Texel and Poll Dorset sired carcasses showed that the Texel cross had a better conformation than Poll Dorset cross amongst both sexes. BLM dams produced carcasses with a superior conformation compared to Merino dams (p < 0.001) in both sexes. BL * M carcasses had a significantly (p < 0.05) smaller M. longissimus thoracis et lumborum area (LL area) than other genotypes, except for M * M ewe carcasses. Texel sired ewe carcasses had a larger LL area (p < 0.05) than those sired by Poll Dorsets, but there was no significant difference for the heavier cryptorchid carcasses. Saleable meat yield for the BL * M carcasses of both sexes was significantly less (p < 0.001) than all other genotypes. M * M carcasses of both sexes produced similar amounts of saleable product to second cross carcasses with the T * M carcasses being superior, resulting in a significant sire breed effect. Texel sired carcasses produced more product than Poll Dorset carcasses. Year had a significant (p < 0.05) effect on all carcass measures and saleable meat yield. Genotype had a significant (p < 0.05) effect on the proportion of each cut except for the neck from cryptorchids and neck fillet from ewes. Texel sired genotypes had significantly (p < 0.05) heavier weights for the hindleg and forequarter cuts than those sired by Poll Dorsets. For the BL * M and m * M genotypes, some of the hindleg cuts, such as the topside and silverside weighed less than other genotypes. The boneless loins from the Poll Dorset genotypes were the heaviest, resulting in a significant (p < 0.05) sire breed effect, with all other genotypes being similar. Models were developed to estimate the yield of cuts and saleable meat using hot carcass weight, GR and other variables. The amount of variation in yield explained by hot carcass weight and GR ranged from r(2) = 0.06 to 0.23. Inclusion of LL area increased the r(2) values up to 0.39. Inclusion of both genotype and year significantly (p < 0.05) improved the prediction of yield, with year contributing the most. The addition of sex had no effect on the prediction of yield. PMID- 22060628 TI - Diverse lamb genotypes-2. Meat pH, colour and tenderness. AB - The effect of genotype on meat ultimate pH, colour and tenderness was studied in 3 experiments involving 436 lambs. The lambs were sired by a selection of Texel (T), Poll Dorset (PD), Border Leicester (BL) and Merino (M) rams, crossed with Border Leicester * Merino (BLM) and Merino (M) ewes giving 6 genotypes (T * BLM, PD * BLM, T * M, PD * M, BLM and M * M). In experiment 1, pH data were obtained for 4 muscles (M. Semimembranosus (SM), M. Biceps femoris M. Semitendinosus and M. Longissimius thoracis et lumborum (LL)) from 198 carcasses representing two sexes (104 cryptorchid males, 94 ewes). There were significant differences for pH between genotypes in both sex groups. BL * M and M * M lambs tended to have higher pH values than the other genotypes. In experiment 2, meat pH, colour using a chromameter, and tenderness data were obtained for 186 lambs representing two sexes (101 cryptorchid males, 85 ewes). There were few significant differences between genotypes for the various meat quality traits amongst the ewes. The PD * BLM ewes had a significantly lower (p < 0.05) pH than the BL * M ewes for the LL and SM muscles. The BL * M crypt orchids had a higher LL muscle pH (p < 0.05) than the PD * BLM cryptorchids with other genotypes being intermediate. There were no significant differences between the genotypes for muscle shear force values. Within experiment 2, LL samples were taken from an additional 52 cryptorchid carcasses these being from 3 specific Poll Dorset sires (experiment 3). One of these sires (sire 3) was suspected of carrying a gene for increased muscling. Sire had a significant effect (p < 0.05) on shear force values, cooking loss and L(*) colour values, but not a(*) or b(*) colour values or pH. Sire 3 progeny had significantly (p < 0.001) tougher LL muscles than those from the other 2 sires. Sire 3 also had the lowest L(*) values, but was intermediate for cooking loss. There was no significant sire effect on LL area at the same carcass weight, but boneless loins from the progeny of Sire 3 were significantly (p < 0.05) heavier. In a fourth experiment, meat colour was measured at three sites (LL, diaphragm and M. Obliquus externus abdominis) on 86 cryptorchid carcasses 24 hr post-mortem. There was little association between L(*), a(*) and b(*) values measured at the different sites. PMID- 22060629 TI - Fatty acid composition and cholesterol content of different ostrich muscles. AB - Six different muscles from the left legs of 19 African Black ostriches were analysed for cholesterol content and fatty acid composition. Cholesterol content differed (p < 0.05) from 56.61 mg/100 g in the M. femorotibialis medius to 71.12 mg/100 g in the M. iliofemoralis. Although the percentage of individual fatty acids differed (p < 0.05) between muscles, and variation were found within muscles, the percentage of total saturated, monounsaturated and polyunsaturated fatty acids were relatively constant between muscles. The M. iliofemoralis presented a w6:w3 ratio of 5.21, while this characteristic was constant around a mean value of 3.93 in all other muscles. PMID- 22060630 TI - Oxazaborolidinium ion-catalyzed cyclopropanation of alpha-substituted acroleins: enantioselective synthesis of cyclopropanes bearing two chiral quaternary centers. AB - A catalytic synthetic route to highly functionalized chiral cyclopropane derivatives was developed by Michael-initiated cyclopropanation of alpha substituted acroleins with aryl- and alkyl diazoacetates. In the presence of chiral (S)-oxazaborolidinium cation 1b as a catalyst, the reaction proceeded in high yield (up to 93%) with high to excellent diastereoselectivity (up to 98% de) and enantioselectivity (up to 95% ee). PMID- 22060631 TI - Incidence, genetics, and clinical phenotype of permanent neonatal diabetes mellitus in northwest Saudi Arabia. AB - BACKGROUND: Permanent neonatal diabetes mellitus (PNDM) in European population has an incidence of at least 1 in 260 000 live births and is most commonly due to mutations in KCNJ11 and ABCC8. However, data on this condition in other populations are limited. OBJECTIVE: To define the incidence, genetic aetiology, and clinical phenotype of PNDM in Al-Madinah region, northwest Saudi Arabia. METHODS: Patients with PNDM diagnosed between 2001 and 2010 were identified and clinically phenotyped. Sequencing of KCNJ11, ABCC8, and INS were performed initially on all subjects, and EIF2AK3, GLIS3, SLC2A2, SLC19A2, GCK, IPF1, and NEUROD1 genes were sequenced according to the clinical phenotype. RESULTS: In total, 17 patients from 11 consanguineous families were diagnosed with PNDM and the incidence was 1 in 21 196 live births. Six different mutations in four genes were identified, of which two GLIS3 and one SLC2A2 were novel and no patient had KCNJ11, ABCC8, or INS mutations. Fourteen (82.4%) patients had identifiable genetic aetiology and their PNDM was part of known autosomal-recessive syndromes including Wolcott Rallison (41.1%), neonatal diabetes and hypothyroidism (29.4%), Fanconi-Bickel (5.8%), and thiamine-responsive megaloblastic anaemia (5.8%). Two patients with isolated PNDM and one with intermediate developmental delay, epilepsy and neonatal diabetes had no identifiable cause. CONCLUSIONS: Al-Madinah region has the highest reported incidence of PNDM worldwide. In this region with high consanguinity, PNDM has different genetic aetiology and in the majority of cases presents as a part of rare familial autosomal-recessive syndrome rather than in isolation. PMID- 22060632 TI - Testing the effect of transient Plio-Pleistocene barriers in monsoonal Australo Papua: did mangrove habitats maintain genetic connectivity in the Black Butcherbird? AB - Changes in climate and sea level are hypothesized to have promoted the diversification of biota in monsoonal Australia and New Guinea by causing repeated range disjunctions and restricting gene flow between isolated populations. Using a multilocus (one mtDNA locus, five nuclear introns) phylogeographic approach, we test whether populations of the mangrove and rainforest restricted Black Butcherbird (Cracticus quoyi) have diverged across several geographic barriers defined a priori for this region. Phylogeographic structure and estimates of divergence times revealed Plio-Pleistocene divergences and long-term restricted gene flow of populations on either side of four major geographic barriers between and within Australia and New Guinea. Overall, our data are consistent with the hypothesis that mesic-adapted species did not disperse across the open dry woodlands and grasslands that dominated the transient palaeo-landbridges during the Plio-Pleistocene despite the presence of mangrove forests that might have acted as dispersal corridors for mesic-adapted species. Our study offers one of the first multilocus perspectives on the impact of changes in climate and sea level on the population history of widespread species with disjunct ranges in Australia and New Guinea. PMID- 22060633 TI - Potential regulatory role of calsequestrin in platelet Ca(2+) homeostasis and its association with platelet hyperactivity in diabetes mellitus. AB - BACKGROUND: Altered Ca(2+) homeostasis contributes significantly to platelet hyperactivity in diabetes mellitus. Calsequestrin (CSQ), as a Ca(2+) buffer protein in the sarcoplasmic reticulum, also regulates the Ca(2+) release process in muscles. We hypothesized that CSQ may be expressed in platelets, but is altered and involved in diabetic platelet Ca(2+) abnormalities and hyperaggregability. METHODS: CSQ expression in platelets from streptozotocin induced type 1 diabetes rats, type 2 diabetes volunteers and Goto-Kakizaki rats were analyzed by western blotting and RT-qPCR. Platelet Ca(2+) and aggregation were evaluated with Fura2 and an aggregometer, respectively. RESULTS: Platelets from diabetic patients and rats exhibited increased resting Ca(2+) levels, and hyperactive Ca(2+) and aggregation responses to agonists. This enhanced basal Ca(2+) was largely dependent on intracellular Ca(2+) and insensitive to inositol 1,4,5-trisphosphate receptor (IP(3)R) antagonism. Additionally, the expression of the skeletal CSQ isotype (CSQ-1) was detected in both rat and human platelets, but its levels were significantly lowered in diabetic platelets as compared with normal platelets. Impairment of CSQ by trifluoperazine caused concentration dependent Ca(2+) release in normal platelets and HEK293 cells. Knocking down CSQ 1 in HEK293 cells resulted in increased leakage of Ca(2+), which was also insensitive to IP(3)R inhibition, and exaggerated Ca(2+) release following carbachol treatment. CONCLUSIONS: Downregulation of CSQ-1 in diabetic platelets and impairment of CSQ-1 in normal cells leads to disturbed Ca(2+) release, demonstrating a potential role for CSQ-1 in the regulation of the platelet Ca(2+) release process and a possible causal contribution to diabetic platelet hyperactivity. PMID- 22060634 TI - Hole transport in triphenylamine based OLED devices: from theoretical modeling to properties prediction. AB - For the series of para-substituted triphenylamines, optimized geometries, HOMO and LUMO energy levels, ionization potentials Ip, reorganization energies for hole transport lambda(+), and frontier orbital contours have been calculated by means of ab initio computations. Relationships between them and the Hammett parameter are presented. According to calculations, electron releasing substituents increase the HOMO and LUMO energies of TPA, while electron withdrawing ones decrease it. This behavior is reflected in subsequent decreasing and increasing of ionization potentials of substituted TPAs. Calculations show that there exists also a strong substituent effect on the reorganization energy lambda(+), which is a dominating factor of hole mobility. It is concluded that proper tuning of the HOMO and LUMO levels (and, as a result, ionization potential, Ip) and reorganization energy lambda(+) (consequently, hole mobility) of the triphenylamine can be done by alteration of the TPA electronic structure by an appropriate substitution. It is demonstrated that the proper adjustment of the HOMO levels of HTM facilitates the reduction of an energy barrier at the interface of ITO/HTL and HTL/EL and ensure the high hole injection and hole transport rate. On the other hand, appropriate adjustment of the LUMO level prevents an electron leak from the EL into the HTM layer. Results of these calculations can be useful in the process of designing new HTM materials of desired properties (high efficiency, stability, and durability). PMID- 22060635 TI - Effective harvesting, detection, and conversion of IR radiation due to quantum dots with built-in charge. AB - We analyze the effect of doping on photoelectron kinetics in quantum dot [QD] structures and find two strong effects of the built-in-dot charge. First, the built-in-dot charge enhances the infrared [IR] transitions in QD structures. This effect significantly increases electron coupling to IR radiation and improves harvesting of the IR power in QD solar cells. Second, the built-in charge creates potential barriers around dots, and these barriers strongly suppress capture processes for photocarriers of the same sign as the built-in-dot charge. The second effect exponentially increases the photoelectron lifetime in unipolar devices, such as IR photodetectors. In bipolar devices, such as solar cells, the solar radiation creates the built-in-dot charge that equates the electron and hole capture rates. By providing additional charge to QDs, the appropriate doping can significantly suppress the capture and recombination processes via QDs. These improvements of IR absorption and photocarrier kinetics radically increase the responsivity of IR photodetectors and photovoltaic efficiency of QD solar cells. PMID- 22060636 TI - Editorial. PMID- 22060637 TI - Consumer expectations and perceptions of meat and meat product quality. AB - This paper presents the determinants of perceived quality viewed by different authors. Then, it sets the factors of quality from purchase to consumption and some mechanisms of change over time. After this general presentation, the distinctive features of food and the particular place of meat and meat products among foods are underlined. Important credence and experience attributes as well as quality cues for meat and meat products are then presented through results from previous works. Finally, the advantages but also the limitations of present methodologies used in quality research are presented and some orientations for future research are suggested. PMID- 22060638 TI - Assuring eating quality of meat. AB - The way of assuring quality has changed over the years, from inspection of end product to quality management systems and on-line process control. The latter concepts have had a great impact in many industries during the last decades. But the concept of Total Quality is continuos improvement so it is time to take advantage of the next generation of quality assurance tools: Quality by Design. This is the most powerful instrument in quality assurance today. Quality by design has been used with outstanding results in many industries as the automobile and the electronics industry. Maybe the meat industry will be the next? To succeed, the "eating quality attributes" that are most important to the customer must be brought into focus. The challenge to the meat research scientist is to design products and processes that take care of customer needs despite variation in the raw material and the consumer's rough handling. The Quality Management Standards are helpful in conducting the design and production process, but to focus on the right aspects, there also are need for suitable methods as Quality Function Deployment. Customer needs change and new research changes old 'truths'. This require an organisation, a quality system and a culture which can handle rapid changes and a diversity of customer needs. PMID- 22060639 TI - Welfare and hygiene during preslaughter handling. AB - This review considers some of the ways in which welfare is compromised during preslaughter handling and it examines some effects of preslaughter handling methods on carcass hygiene. There are many ways in which animals suffer during the preslaughter period. They include metabolic exhaustion, dehydration, death during transport, emotional and temperature stress, bruising, torn skin, and, sickness and disease. Recent research findings on the effects of preslaughter stress on muscle glycogen metabolism and dark firm dry meat are reviewed. PMID- 22060640 TI - Interruption of microbial cycles in farm animals from farm to table. AB - The fact that only slight problems are posed by Salmonella, Campylobacter and Escherichia coli O157 in mammalian farm animals in Norway, is undoubtedly due in large degree to the agricultural set-up with small farms and small herds, allowing a good overview of the situation at any time. Other factors are the very limited import of breeding animals and food products of animal origin, microbiological control of animal feed, and favourable geographical and climatic conditions. However, the Norwegian meat industry (including abattoirs) has continuing problems with Yersinia enterocolitica O:3 in pigs and pig meat, and in some cases with Listeria monocytogenes in cold cuts and Toxoplasma gondii in sheep meat (lamb). These three agents are therefore used to illustrate appropriate measures to be taken at the herd level on the farm, in abattoirs and in the meat processing industry. PMID- 22060641 TI - Microorganisms in fresh ground meats: the relative safety of products with low versus high numbers. AB - The two outbreaks of haemorrhagic colitis (HC) that were traced to ground beef in 1982 were the first foodborne cases known to be caused by Escherichia coli 0157:H7. The 1993 outbreak in the U.S. Pacific Northwest is the largest foodborne disease outbreak ever traced to ground beef. Why these events occurred continues to be a matter of speculation and debate. It is the thesis of this review that HC causing strains of E. coli, which could have been in the meat supply as early as the mid-1950s, can persist in meats that contain too few of the background bacterial biota. The antagonistic effect of background organisms against pathogenic bacteria (microbial interference) is well established. Fresh ground meats that contain 10(5)-10(6)/g of background organisms are inherently safer than those that contain, say, 10(3)/g. Although the production of fresh ground meats with as few microorganisms as possible would seem to be the ideal, there is little or no evidence to support the superior safety of such products. It is suggested that when pathogen-reduction strategies are applied to animal carcasses, the carcasses should be 'protected' against subsequent colonization by pathogens by actually adding appropriate mixtures of harmless bacteria. PMID- 22060642 TI - Structural weakening of skeletal muscle tissue during post-mortem ageing of meat: the non-enzymatic mechanism of meat tenderization. AB - Structural weakening of the myofibrils, the intermediate filaments and the intramuscular connective tissues the endomysium and perimysium contribute to tenderization of meat during post-mortem ageing. We have found four phenomena which effect the structural weakening of myofibrils: weakening of Z-disks, weakening of rigor linkages formed between actin and myosin, splitting of connectin (titin) filaments, and fragmentation of nebulin filaments. These reactions are specific to 0.1 mM calcium ions regardless of proteolysis. Desmin molecules which form intermediate filaments are also fragmented by 0.1 mM calcium ions nonenzymatically. The fragmentation of desmin molecules suggest depolymerization of intermediate filaments under non-physiological conditions. These facts are the basis of 'the calcium theory of meat tenderization' which I have proposed. The structural weakening of the endomysium and perimysium shows the effect on tenderization of extended ageing of meat, and is closely related to degradation of proteoglycans which link collagen fibrils and stabilize collagen fibres. PMID- 22060643 TI - Recent advances in process assessment and optimisation. AB - After stating the general principle of food preservation, this paper focuses on currently available methods to evaluate quantitatively the integrated time temperature impact during and/or after a thermal preservation process. In this context, both the physical-mathematical approach and the use of time temperature integrators are briefly reviewed and recent evolutions are indicated. Also new trends with regard to thermal process optimisation are highlighted. PMID- 22060644 TI - Extending the storage life of raw chilled meats. AB - Preservative packagings for raw meats must both delay the deterioration of the appearance of the product and retard the onset of bacterial spoilage. Preserving the product appearance is largely a matter of slowing or preventing the formation of brown metmyoglobin at muscle surfaces. Browning is slowed in atmospheres which are rich in oxygen, and persistent browning is entirely prevented when meat is packaged under oxygen-depleted atmospheres. Bacterial spoilage is delayed by packaging under aerobic atmospheres rich in carbon dioxide, or by packaging under anaerobic conditions. However, the control of bacterial spoilage also requires that product temperatures be maintained close to the optimum for chilled storage, and attention to the hygienic condition of the product before it is packaged. Packaging techniques for conforming an extended storage life on most raw meats are available, and long term economic trends seem to require a general improvement of the storage life of raw meats. However, current commercial systems for distributing meat are largely geared to the handling of highly perishable product, and the potential economic advantages from trading in more stable product will not be fully realizable while such systems persist. Consequently, commercial progress towards greater storage stability for chilled meats is likely to be uneven and uncertain. PMID- 22060645 TI - Oxidative quality and shelf life of meats. AB - Lipid oxidation is one of the primary mechanisms of quality deterioration in foods and especially in meat products. The changes in quality are manifested by adverse changes in flavor, color, texture and nutritive value, and the possible production of toxic compounds. Lipid oxidation in muscle systems is initiated at the membrane level in the intracellular phospholipid fractions. How this occurs has still not been resolved, although it is generally believed that the presence of transition metals, notably iron, is pivotal in facilitating the generation of species capable of abstracting a proton from an unsaturated fatty acid. This paper provides an overview of how lipid oxidation affects the quality and shelf life of meat and meat products, and how shelf life can be extended through dietary vitamin E supplementation above requirement levels. The formation of cholesterol oxidation products and the possible role of lipids and their oxidation products in the formation of heterocyclic aromatic amines are also discussed. PMID- 22060646 TI - Hot processing of meat. AB - Economical advantages favour hot processing of meat. Losses during chilling, cost of refrigeration, labour and transportation can be considerably reduced giving to meat processors extra value. However, several technical and technological problems delay implementation of this technology by industry. Beginning with cost of investment necessary to retrofit facilities into hot processing of meat, synchronizing organization of work at the factory according to this technology, and finally to insure the required, stable quality of meat and meat products. Therefore, before full industrial implementation several technological problems still should be solved in laboratory and pilot plant experiments and confirmed at full factory scale. This paper reviews the latest research publications on hot processing of meat. PMID- 22060647 TI - Multivariate techniques in the analysis of meat quality. AB - The present paper discusses the use of multivariate statistical methods in meat science. Three examples are given illustrating some of the most important areas of use. The three examples are i) interpretation of large data matrices, ii) prediction of chemical constituents from multivariate spectral data and iii) finding relationships between multivariate data matrices. PMID- 22060648 TI - In-line image analysis in the slaughter industry, illustrated by Beef Carcass Classification. AB - This paper describes a complete framework for the quantitative quality control of biological objects using computer vision. The techniques are described in the context of BCC-2, the second generation Beef Carcass Classification centre, which has operated as a prototype since March 1995. Installed in the slaughterline, BCC 2 analyses one half, dehided carcass. BCC-2 determines the visual properties: conformation, fatness and fat colour as well as objective quantities such as the percent of saleable meat and the cross sectional area of the rib eye. BCC-2 measures geometry and colour quantitatively. A procedure for maintaining the same calibration over time for several BCC-2 units has been developed. BCC-2 is built from a few inexpensive components: A frame that positions the half carcass in the slaughterline, a camera, two PC's, and a terminal. In addition, two slide projectors project stripes of light onto the carcass at an angle to the camera to provide information about the three-dimensional shape. The biological variation of the carcasses requires the use of advanced information processing techniques: traditional pattern recognition, principal component analysis, and neural networks. BCC-2 is adaptive, i.e. it is trained by examples, and BCC-2 is robust in the sense that it classifies all carcasses except the ones most damaged in the slaughter process. PMID- 22060649 TI - Recent developments in sheep and beef processing in Australasia. AB - New Zealand and Australia have invested heavily in the development of slaughter, dressing and deboning equipment for sheep and beef. A number of sheep dressing and deboning machines are now in commercial use after completing their development. The success of some of these developments has encouraged further investment in sheep dressing and deboning and beef deboning developments. Many of these developments will be ready for commercial use within the next two years. PMID- 22060650 TI - Biophysical aspects of meat tenderness. AB - Biophysical aspects of meat tenderness is reviewed, where the meat structural origin of variation in meat tenderness is tried to be elucidated. Processes, such as rigor development and ageing, known to influence the properties of the structural components, is covered, and variables that influence those processes, such as chilling, electrical stimulation and stress ante-mortem, are discussed. Meat tenderness can be evaluated both by sensory and instrumental methods. The relationships between mechanical and sensory assessments tend to be non-linear, which can be due to non-linearity in the sensory evaluation and that muscle fibre orientation is easier to control in instrumental than in sensory evaluation. Structural changes of the meat occuring during rigor development are both longitudinal and lateral contraction of the myofibrillar mass. Other structural events, based on the proteolytic action, are the loosing up of the myofibrils held together laterally, weakening of the myofibrillar length and myofibril fragmentation. Using instrumental recordings of meat toughness (Warner-Bratzler (W-B) peak force), it decreases significantly with degree of contraction, when raw, but the reverse is found, when meat is cooked above 60 degrees C. A structural explanation to this behaviour is suggested to be the following. When meat is raw the lateral contraction of the meat fiber increases with shorter sarcomeres, giving rise to a larger viscous component and hence a lower W-B peak force. On heating, however, with a larger extracellular space, when shortened, there is more room for the connective tissue to contract without being restricted by the myofibrillar mass. This in turn gives a higher number of fibers per unit cross-sectional area, hence a larger elastic modulus and a higher W-B peak force, when cooked. When chilling of muscle during rigor both warm- and cold-shortening occur. Minimal shortening region is for beef M. longissimus dorsi (LD) 10-15 degrees C and for M. semimembranosus (SM) 7-13 degrees C. For the SM muscle there is a high correlation between percentage shortening and ultimate tenderness both in the warm- and cold-shortening region. But for the LD muscle this is only the case in the cold-shortening region. This observation suggests that the LD muscle is a more enzymatically active muscle than SM. The influence of low voltage electrical stimulation (ES) was followed in the cold-shortening region for muscles LD and SM. A significant effect on tenderness 15 days post-mortem was only observed for LD at 1 degrees C and 4 degrees C, but not for SM. It was suggested that enhanced proteolysis could be the reason for the improved tenderness on ES of LD, as colds-hortening was not prevented by ES. Long-term and short-term stress ante-mortem can give rise to DFD (dark, firm and dry)-and PSE (pale, soft and exudative)-meat, respectively. DFD-meat (pH(u) > 6.0 in LD) has relatively short sarcomere lengths, but still it is swollen laterally and has consequently a small extracellular space. Therefore DFD-meat usually is tender. PSE-meat has a large variation in sarcomere length. The long sarcomeres of PSE meat is suggested to be caused by reduced shortening, due to the denaturation of the sarcoplasmic proteins during rigor. The short sarcomeres can be caused by a higher percentage of rigor development in the warm-shortening region and that the denaturation of the myosin heads cause both longitudinal and lateral contraction of the myofibrillar mass. There is also a large variation in tenderness of PSE meat, but it has been found that this variation is positively correlated to the sarcomere length (r = 0.52**), as has been shown for the other variables that governs the rigor process. PMID- 22060651 TI - Biochemical factors regulating the toughening and tenderization processes of meat. AB - The purpose of this manuscript is to present a brief review of the biochemical basis for longissimus toughening and tenderization processes. Also, to explore the potential technologies that can be developed based on this knowledge to reduce variation in tenderness, thus, improving consumer acceptance of meat. Results suggest that after slaughter longissimus has low to intermediate shear force values (probably tender). Rigor development-induced changes increase its shear force. Maximum toughness is observed between 12 to 24 h post mortem. The toughening process seems to occur equally in all carcasses. Post-mortem storage at refrigerated conditions tenderizes longissimus. Post-mortem tenderization is caused by enzymatic degradation of key myofibrillar and associated proteins. The function of these proteins is to maintain the structural integrity of myofibrils. Current data indicates that MU-calpain is responsible for degradation of these proteins. Unlike the toughening process, there exists a large variation in the rate and extent of tenderization which is responsible for variation in tenderness at the consumer level. Potential strategies for the control of the variation in meat tenderness are discussed. PMID- 22060652 TI - The chill chain "from carcass to consumer". AB - To provide safe meat and meat products of high organoleptic quality, attention must be paid to every aspect of the chill chain. The process commences with the initial chilling of the freshly slaughtered carcass and continues through to the storage of the chilled retail portion within the home. Within the chill chain are two different categories of refrigeration processes. In the first group are those such as primary and secondary chilling, where the aim is to change the average temperature of the meat. In the others, such as chilled storage, transport and retail display, maintaining the initial temperature of the meat or meat product is the prime aim. Failure to understand the needs of each process results in excessive weight loss, higher energy use, reduced shelf life or a deterioration in product quality. PMID- 22060653 TI - Very fast chilling of beef and tenderness-a report from an EU concerted action. AB - Very Fast Chilling (VFC) in Beef is a European Union funded concerted action begun in November 1994. Scientists from the Union have met several times to review their work. Muscle is defined as VFC when it is chilled to -1 degrees C by 5h post mortem. The sub-zero conditions necessary will produce temperature gradients in all muscles and these give rise to considerable variation in biochemical and physical parameters. Calcium ions released by the cold within muscle fibres stimulate proteolytic action which tenderises the meat, but also stimulate contraction which toughens meat. The studies considered here suggest that a combination of proteolysis and crust freezing can produce tender beef. More research is needed into the biochemical mechanisms and pilot scale investigations could be undertaken. The early cutting and processing of the beef side would improve abattoir efficiency but VFC technique is not yet ready for full-scale industrial implementation. PMID- 22060654 TI - Accelerated production of dry fermented sausage. AB - The scope of this paper is to review work connected with accelerated ripening of dry fermented sausages by addition of proteolytic enzymes. An overview of the following topics is given: practical sausage experiments with addition of various proteinases of bacterial origin, including data from sensory, biochemical and gc/ms analyses; biochemical and genetic characterization of the enzyme shown to be most useful in these experiments, the serine proteinase from Lactobacillus paracasei subsp. paracasei NCDO 151; experiments to transform starter cultures with the genes for production of this proteinase and proposals for future work in this field. PMID- 22060655 TI - Engineering aspects in fermentation of meat products. AB - This paper focuses on the engineering aspects of the drying and ripening process of dry sausages. It describes the physical and chemical phenomena during the ripening time. The influence of the intrinsic and extrinsic control quantities of the dry sausage ripening on the mass transfer parameter in the sausages is determined. Measuring techniques and experiments for the examination of these parameters are introduced and the influence of the parameters on the drying explained. Mathematical tools for numerical simulations and their application to the above mentioned problems are described. For the problem of inhomogeneous drying of dry sausages in industrial ripening chambers, solutions will be suggested. PMID- 22060656 TI - Pre-slaughter handling of reindeer-effects on meat quality. AB - The centralization of the slaughter industry has created one of the biggest problems for beef quality, namely dark-cutting or DFD. After studying the various handling routines and their effects on meat quality, it was found possible, by applying simple and clearcut rules, to minimize the DFD frequency in beef. We then started to scrutinize the slaughter procedure for reindeer, as we realized that new directives in Sweden would lead to centralization of the slaughter industry. Before the new directives were introduced we obtained sufficient funding to set up a four-year research project dealing with old and new slaughter handling procedures for reindeer and their effects on meat quality. The overall objective was to devise simple and effective rules for the handling of slaughter reindeer in order to avoid meat quality deterioration. Various preslaughter handling routines for reindeer, such as gathering and herding, selection, feeding, road transport and lairage, imply stressful events which can affect glycogen stores in muscle and hence meat quality. During a 3 day helicopter drive (20 km/day), we found no negative effects on glycogen stores or ultimate pH values. Lorry transport of reindeer over various distances (0 up to 1000 km) did not cause any increase in ultimate pH values in bulls and calves, though cows did show a slight increase in pH. A 2-day pre-slaughter waiting period at a slaughterhouse, where the reindeer were fed hay and water, caused no deleterious effects on muscle glycogen content or pH. Sorting out reindeer by use of the traditional lasso technique, however, seems to be the only handling procedure so far studied causing considerable physical and mental stress leading to muscle glycogen depletion and dark-cutting. The effects of various handling procedures are very much dependent on the physical condition of the animals. From our studies we can conclude that feeding has a major influence on physical condition, muscle glycogen content and hence meat quality. PMID- 22060657 TI - Processing of marine foods. AB - For the Norwegian fish industry, it is an objective to increase the production of value added products in order to improve profitability. This paper will briefly present four areas of important research tasks in this field. To aid in the identification of the species present in a product, we have applied the method called Random Amplification of Polymorphic DNA (RAPD). This technique is used to produce a fingerprint of DNA contained in the sample. The application of DNA typing for species identification in fish products is presented. The nutritional aspects of foods are important. Although the low death rate from coronary heart disease among the Eskimos of Greenland has been suggested to stem in large part from their consumption of fish, one should keep in mind that the daily diet of Eskimos living in the traditional way consists of substantial quantities of meat and fat (blubber) from seals and whales. A recent study as to whether seal and whale oils are more effective than cod liver oil in changing biological parameters that might be important in explaining low incidence of coronary heart disease, asthma and psoriasis among Greenland Eskimos will be presented. Commercial processing of fish must take the development of rigor mortis into consideration since it affects yield and fish flesh quality. Influence of early processing (pre-rigor) on fish quality and yield is also discussed. There are significant differences among fish species in gross chemical composition and morphological structure. Depending on the properties of the flesh and the way it is treated, it may gain or lose water. The relationship between structure and liquid-holding properties of cod and salmon muscle as a function of temperature is presented. PMID- 22060658 TI - Authenticity issues in meat and meat products. AB - Proper product description is of crucial importance in ensuring fair trading practices and enabling consumers to make informed choices and is therefore addressed in some detail in UK food legislation. This paper will briefly examine the historical development of UK food laws and the meaning of "authenticity" within the context of current legislation, particularly with respect to meat and fish products. The food authenticity programme of the UK Ministry of Agriculture, Fisheries and Food (MAFF) is discussed, outlining its R and D programme and detailing the types of topics under consideration, and how selection of surveillance projects is determined. PMID- 22060659 TI - Early Post Mortem pH decrease in porcine M. longissimus dorsi of PSE, Normal and DFD quality. AB - The purpose of this investigation was to compare the muscle pH at exsanguination and the rate of pH changes in porcine M. longissimus dorsi (LD) of normal, DFD (Dark, Firm, Dry) and PSE (Pale, Soft, Exudative) quality. The pH was continuously measured in the LD in 116 carcasses during the first 50 min post mortem. Calculations were made both on measured pH-values and on pH-values transformed to hydrogen ion concentrations. A regression of pH or hydrogen ion concentration on time was made for each animal. These individual regressions were then combined, using a multivariate analysis to estimate regression curves for each meat quality class. The two methods for expressing pH gave somewhat different results. The relationship between the hydrogen ion concentration and time was found to be linear for normal and DFD muscles and quadratic for PSE muscles. As a consequence of the mathematical properties of pH, the relationship between pH and time was found to be quadratic for the normal and DFD qualities, and linear for the PSE quality. For both methods of calculations the slopes for the regression curves were significantly different between PSE and the other two quality classes with both calculating methods, while the slopes did not differ between normal and DFD muscle qualities. The intercepts of the regression curves differed significantly between PSE and the other two quality classes only when the calculations were made on measured pH-values without transformation. A temporary increase in pH was seen in some normal and PSE carcasses during the measured time period. Development of muscles with PSE characteristics thus seems to be initiated by a combination of a lower muscle-pH already at exsanguination and a faster pH decrease. It is also of importance to consider the special mathematical properties of the pH-value. PMID- 22060660 TI - Model system evaluations of the effects of different levels of K(2)HPO(4) NaCl and oil temperature on emulsion stability and viscosity of fresh and frozen turkish style meat emulsions. AB - The effects of different levels of K(2)HPO(4), NaCl, and the effects of oil temperature used in the evaluation of emulsion stability and viscosity of fresh and frozen beef (fat level adjusted with tail fat from sheep) was studied by utilizing a model system. Emulsion stability (ES) and emulsion viscosity (EV) of frozen meat tissue were both decreased, by 3.6% and 10.5% respectively, when compared to fresh meat. ES was decreased by 4.0% and 3.7% at 5 degrees C and 11 degrees C oil temperature respectively when compared to 21 degrees C. While EV decreased 12.2% at 11 degrees C compared to 21 degrees C, it did not show any statistically significant (P < 0.01) change at 5 degrees C oil temperature. ES and EV were elevated with the addition of phosphate and increasing phosphate levels. These increases for ES were 3.9% and 3.7% with 0.50% and 0.75% phosphate levels respectively, when compared to the 0.00% phosphate control group. Also, the increases for EV were 22.3% and 27.0% with 0.50% and 0.75% phosphate levels respectively, compared to the 0.00% phosphate control group. The alteration of the ES was not statistically P < 0.01) significant for the 0.50% phosphate level when compared to the 0.75% phosphate level. The ES decreased 1.1% for a 3.0% salt level when compared to a 2.5% salt level, and there was statistically (P < 0.05) no effect on the EV. PMID- 22060661 TI - Further investigations into the relationship between ultimate pH and tenderness for beef samples from bulls and steers. AB - Samples of longissimus dorsi muscle from 150 cattle comprising Friesian bulls and steers and Charolais * Angus cross steers, were used to investigate the nature of the relationship between ultimate pH and beef tenderness under conditions where cold-shortening was avoided. A modified Warner-Bratzler (WB) shear machine with a square- rather than a vee-blade enabled several aspects of tenderness to be evaluated, including peak force (PF), initial yield force (IY), PF-IY, and an index of total work done. The two steer groups differed little in meat quality characteristics, but, in terms of six major hindquarter cuts, the Charolais cross group yielded 14.3% more meat per unit live weight, due to a combination of a superior dressing-out percent and a higher cutability. Relative to Friesian steers, the bulls produced beef with a higher ultimate pH (P < 0.001), and after adjustment to a common pH, the bull beef was tougher for all WB parameters except PF-IY. Cooking loss was higher for beef from bulls after adjustment for pH. Although reduced by pH adjustment, beef from bulls remained significantly darker than that from steers (P < 0.05) based on reflectance measurements. Maximum toughness in terms of PF, IY, and work index was at an ultimate pH of 6.0-6.1, but the peak was much less clear for PF-IY. The decline in tenderness with an increase in ultimate pH to 6.2 was associated with a decrease in sarcomere length. This result supports a previous suggestion that shortening explains, at least in part, the lower average tenderness at intermediate pH values. PMID- 22060662 TI - Prediction of meat quality in live pigs using stress-susceptible and stress resistant animals. AB - A new in-vivo procedure for predicting the potential meat quality in live pigs was devised using stress-susceptible (halothane positive) and stress-resistant (halothone negative) pigs. The potential meat quality in live pigs was determined using small biopsy samples of M. longissimus dorsi (LD). Meat quality was assessed by the combined measurements of pH and water-holding capacity (WHC) on the 12 000 g supernatant after incubation of 500 mg biopsy LD muscle with an equal volume of 150 mm KCl at 39 degrees C for 45 min. With the LD muscles of halothane positive (n = 37) and halothane negative (n = 55) pigs, high correlations (r = -0.854) were observed between the supernatant (i.e. fluid) pH and WHC of the biopsy samples, between fluid pH of the biopsy samples and 1-h post-mortem (pH(60)) LD muscles (r = 0.951), and between pH(60) and WHC (r = 0.956). The experimental data show that our in-vivo test can differentiate halothane positive from halothane negative pigs and can also predict the potential meat quality in live pigs. The test could be applied to select pigs with differences in WHC to improve meat quality. PMID- 22060663 TI - A study of changes in the fat content of some varieties of dry sausage during the curing process. AB - The influence of the curing of dry sausage (chorizo, saucisson, salami) on the chemical composition of lipids was studied in terms of what affects the oxidation and resulting production of volatile aldehydes, mainly hexanal. Microbial fermentation initially increases the unsaturation, although this phenomenon is reversed during the drying-curing process. In this phase the saturation/unsaturation ratio rises in C16 and C18 fatty acids, the increase being higher in chorizo and lower in salami. Stearic acid appears to increase more than palmitic acid, and C16 quotient values show significant differences across a range of commercially-sold brands of each type of sausage. Unsaturation varies in parallel with the iodine value in the three cases studied. Lipolytic phenomena produce fatty acids with a greater amount of linoleic acid than oleic acid. The oxidation of these fatty acids is progressive regardless of whether TBA or carbonyl values are measured. Nevertheless, significant correlations of hexanal concentrations are not evident. The formation of butanal and pentanal (<2 MUmol) is very low, and hexanal concentration fluctuates (11-111 MUmol) among commercial brands and types of sausage. These concentrations are always much higher in chorizo samples than in those of salami. Statistical multivariant analysis highlights the greater significant differences in salami samples, a sausage which reflects the lack of homogeneity between different industrial processes. PMID- 22060664 TI - Effect of the addition of pronase E on the proteolysis in dry fermented sausages. AB - The effect of the addition of pronase E at two different concentrations on protein breakdown during the ripening of dry fermented sausage was studied. In all batches, water-soluble, non-protein and 5% phosphotungstic acid soluble nitrogens increased sharply during the first days of ripening, then became stabilized until the end of the process (26th day), and the total volatile nitrogen consistently increased during ripening. The greater the pronase E added the higher were the values reached for all these fractions. The changes in total free amino acids showed a similar pattern to that observed for the phosphotungstic acid soluble nitrogen. Histamine and tyramine progressively increased throughout the ripening. By sensory evaluation, no significant differences between the control batch and the batch with the lowest amount of added pronase E were found, but both batches were significantly different (P < 0.1) from the batch manufactured with the highest concentration of pronase E, which was classed as objectionable by the panellists because of its excessive softness. PMID- 22060665 TI - Modelling post-mortem tenderisation-IV: Role of calpains and calpastatin in conditioning. AB - A generalised model, based on published data, was developed quantifying the mechanism by which the activities of calpains I and II are responsible for post mortem tenderisation. Tenderisation is proposed to result from the activities of 'free' activated-calpains, the activities of which are controlled by the changes in the calcium ion concentration, the binding of calpains to calpastatin, the inactivations of 'free' activated-calpains and their proteolysis of calpastatin. At the low myoplasmic ('free') calcium ion concentrations prevailing soon after slaughter, calpains are largely 'inert' and little tenderisation occurs. As the pH declines, the 'free' calcium ion concentration rises and activates calpain I: however, most of this activated-calpain I is then bound to calpastatin. With a futher decline in pH, the binding of activated-calpain I to calpastatin is reduced and the level of 'free' activated-calpain I rises and tenderisation increases. A comparable process occurs with calpain II at higher 'free' calcium ion concentrations which occur as the pH declines further. As the level of 'free' activated-calpains rises, their proteolysis of calpastatin also increases, causing a lowering of levels of calpastatin and reducing the inhibition of calphins. Concurrently, 'free' activated-calpains are inactivated. This balance between inhibition, inactivation and activity of calpains and their decrease as the pH declines maintains the proteolytic activity of calpains and produces the gradual process of tenderisation, initially by calpain I and at the later stages mainly by calpain II. Eventually, the activities of calpains decline to zero and tenderisatin stops. Equations were derived to describe the changes from stunning to the completion of conditioning, and parameters were calculated to determine the activities of calpains and tenderisation in beef M. longissimus dorsi. PMID- 22060666 TI - Influence of freezing method on thaw drip and protein loss of low-voltage electrically stimulated and non-stimulated sheeps' muscle. AB - South African Mutton Merino wethers (n = 32) were slaughtered, yielding carcasses with a mean weight of 22.18 +/- 2.11 kg. Sixteen carcasses were electrically stimulated (ES) (21 V, 60 Hz, 120 s) immediately and all carcasses were chilled at room temperature (16 degrees C) for 3 h and then overnight at 4 degrees C, 95% RH. Both left and right Mm. longissimus lumborum et thoracis were excised and cut into six portions (77 g +/- 7.8 g), each placed separately in a polyethylene bag and randomly allocated to five freezing treatments. These were: (1) cryogenic, 65 degrees C; (2) cryogenic, -90 degrees C; (3) walk-in-freezer, -21 degrees C; (4) blast freezer, -21 degrees C; (5) domestic freezer, -25 degrees C. The respective freezing rates were 4.4, 6.4, 0.55, 0.35 and 0.51 cm h(-1) to -2.2 degrees C at core depth of 1 cm below the surface. Samples were frozen to core temperatures of -20 degrees C, removed and placed in a storage freezer (-20 degrees C) for 48 h and 2.5 months. Samples were then suspended in perforated bags in a chiller (4 degrees C) to thaw, and drip was collected in outer bags over the periods 0-24, 24-48, 48-72 and 72-96 h and expressed as g (100 g)(-1). Freezing methods had significant (P < 0.01) influences on drip loss in both ES and NES samples. Following storage for 48 h post-freezing at -20 degrees C, total drip (g (100 g)(-1)) over 96 h of both ES and NES samples for the five freezing treatments were respectively: (1) 7.61 and 4.61; (2) 7.35 and 3.29; (3) 9.44 and 4.68; (4) 9.07 and 5.43; (5) 10.58 and 5.15. Following storage for 2.5 months, the total ES and NES drip were respectively, (1) 11.25 and 9.38; (2) 10.36 and 9.15; (3) 13.72 and 12.65; (4) 13.70 and 12.26; (5) 11.92 and 11.29. Total protein in the drip did not differ between freezing treatments. Differences between ES and NES samples did occur in the 48 h storage group. It is concluded that cryogenic freezing results in less thaw drip than the vapour compression systems. This advantage of cryogenic freezing disappears if meat is stored for long periods at -20 degrees C. Electrical stimulation increases the drip loss in samples frozen for 48 h, but the differences are not significant after 2.5 months frozen storage. Protein losses parallel the drip. PMID- 22060667 TI - Antioxidant activity of carnosine in cooked ground pork. AB - Carnosine (0.5-1.5%) reduced (P < 0.05) the formation of thiobarbituric acid reactive substances (TBARS) in cooked unsalted ground pork after 7 days of storage at 4 degrees C. The antioxidant activity of carnosine was less in cooked salted ground pork, with only 1.5% carnosine inhibiting (P < 0.05) TBARS formation during refrigerated storage. The antioxidant activity of carnosine in cooked salted and unsalted ground pork was greater than those of the lipid soluble free radical scavengers, butylated hydroxytoluene and alpha-tocopherol (P < 0.05) but less than that of sodium tripolyphosphate (P < 0.05). These data suggest that carnosine could be used to reduce the oxidative deterioration of cooked salted and unsalted ground pork. PMID- 22060668 TI - Comparison of dry sausages produced by different methods: Addition of nitrite/nitrate salts and sodium chloride at different phases. AB - Two processes for Spanish dry sausage manufacture, which differed only in the time of addition of nitrite/nitrate salts and sodium chloride (Type A: in the cutter; Type B: in the kneading machine) were studied. There were no significant differences in parameters related to product stability, pH or water activity. Water-holding capacity and nitroso heme pigment formation were better in type B. The intensity of proteolysis and the insolubilization of myofibrillar protein over the curing period were higher in type A. Iodine value and the relative percentage of polyunsaturated free fatty acids were higher in type B sausages at the end of the curing. Parameters related to protein integrity and the nature of the fat seem to be the main cause of the observed differences between the two types of dried samples. PMID- 22060669 TI - Lipid emboli distribution in cardiac surgery is dependent on the state of emulsification. AB - OBJECTIVE: Lipid embolizations from retransfused shed blood during cardiac surgery have been shown to enter the circulation and end up in different organs. The purpose of this investigation was to evaluate differences in the kinetics and deposition between emulsified and non-emulsified lipid emboli in a porcine model. DESIGN: Twelve animals were anesthetized and put on cardiopulmonary bypass. A shed-blood phantom (6 animals given emulsified and 6 given non-emulsified lipids) was produced from arterial blood, saline, and tritium-labeled triolein. The phantom was infused into the cardiopulmonary bypass circuit. Arterial and venous blood samples were taken at short intervals. Tissue samples were taken post mortem from examined organs and prepared for scintillation counting. Levels of radioactivity were used to measure lipid emboli content in blood and tissue. RESULTS: Emulsified lipid emboli generated a 5-fold higher embolic load in the arterial and a 12-fold higher in the venous circulation, compared with non emulsified lipid emboli. Emulsified lipid micro emboli resulted in a 2-15-fold higher tissue deposition in investigated organs compared with non-emulsified lipid micro emboli. CONCLUSIONS: This study shows that the state of emulsion significantly alter the kinetics and tissue deposition of lipid emboli. Emulsified lipid emboli give higher embolic load in the arterial and venous circulation, and higher tissue deposition versus non-emulsified lipid emboli. In both groups, the embolic load was higher in the arterial circulation than on the venous side. PMID- 22060670 TI - Disruption in Bruch membrane in patients with Stargardt disease. AB - PURPOSE: To describe the spectral domain-optical coherence tomography (SD-OCT) findings of two patients with complete defects in the retinal pigment epithelium (RPE) with disruptions in Bruch membrane in Stargardt disease (STGD1). METHODS: Two patients with STGD1 were referred to our clinic for further evaluation. Fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD OCT), electroretinography (ERG) and Microperimetry (MP-1) were performed to assess the retinal anatomy and function. Screening for mutations in the ABCA4 gene was carried out and detected mutations were confirmed by direct sequencing. RESULTS: Both patients had bilateral macular geographic atrophy (GA) and yellowish subretinal pisciform flecks and mutations were detected in the ABCA4 gene by chip screening. SD-OCT revealed marked atrophy of the retina in the central macula, with focal defects in the RPE with disruptions in Bruch membrane and herniation of the retina through the defect in three of four eyes. CONCLUSION: This case report highlights the necessity for a detailed ophthalmic examination including SD-OCT of patients with STGD1. PMID- 22060671 TI - Realization of process improvement at a diagnostic radiology department with aid of simulation modeling. AB - Using the classical process improvement framework of Plan-Do-Study-Act (PDSA), the diagnostic radiology department of a tertiary hospital identified several patient cycle time reduction strategies. Experimentation of these strategies (which included procurement of new machines, hiring of new staff, redesign of queue system, etc.) through pilot scale implementation was impractical because it might incur substantial expenditure or be operationally disruptive. With this in mind, simulation modeling was used to test these strategies via performance of "what if" analyses. Using the output generated by the simulation model, the team was able to identify a cost-free cycle time reduction strategy, which subsequently led to a reduction of patient cycle time and achievement of a management-defined performance target. As healthcare professionals work continually to improve healthcare operational efficiency in response to rising healthcare costs and patient expectation, simulation modeling offers an effective scientific framework that can complement established process improvement framework like PDSA to realize healthcare process enhancement. PMID- 22060672 TI - Primary leiomyosarcoma of the breast. PMID- 22060676 TI - Genome-wide analysis of chromatin features identifies histone modification sensitive and insensitive yeast transcription factors. AB - We propose a method to predict yeast transcription factor targets by integrating histone modification profiles with transcription factor binding motif information. It shows improved predictive power compared to a binding motif-only method. We find that transcription factors cluster into histone-sensitive and insensitive classes. The target genes of histone-sensitive transcription factors have stronger histone modification signals than those of histone-insensitive ones. The two classes also differ in tendency to interact with histone modifiers, degree of connectivity in protein-protein interaction networks, position in the transcriptional regulation hierarchy, and in a number of additional features, indicating possible differences in their transcriptional regulation mechanisms. PMID- 22060677 TI - Depression after low-energy fracture in older women predicts future falls: a prospective observational study. AB - BACKGROUND: Falls are one of the main causes of fractures in elderly people and after a recent fracture, the risk of another fall is increased, resulting in subsequent fracture. Therefore, risk factors for future falls should be determined. We prospectively investigated the relationship between depression and the incidence of falls in post-menopausal women after a low-energy fracture. METHODS: At baseline, 181 women aged 60 years and older who presented with a recent low-energy fracture were evaluated at the fracture and osteoporosis outpatient clinics of two hospitals. As well as clinical evaluation and bone mineral density tests, the presence of depression (measured using the Edinburgh Depression Scale, EDS, depression cut-off > 11) and risk factors for falling were assessed. During two years of follow-up, the incidence of falls was registered annually by means of detailed questionnaires and interviews. RESULTS: Seventy nine (44%) of the women sustained at least one fall during follow-up. Of these, 28% (n = 22) suffered from depression at baseline compared to 10% (n = 10) of the 102 women who did not sustain a fall during follow-up (Chi(2) = 8.76, df = 1, p = .003). Multiple logistic regression showed that the presence of depression and co morbidity at baseline were independently related to falls (OR = 4.13, 95% CI = 1.58-10.80; OR = 2.25, 95% CI = 1.11-4.56, respectively) during follow-up. CONCLUSIONS: The presence of depression in women aged 60 years and older with recent low-energy fractures is an important risk factor for future falls. We propose that clinicians treating patients with recent low-energy fractures should anticipate not only on skeletal-related risk factors for fractures, but also on fall-related risk factors including depression. PMID- 22060678 TI - Evaluation of different systems for the identification of Bacillus strains isolated from Spanish fermented sausages. AB - Sixty-nine isolates obtained during the manufacture and ripening of Spanish fermented sausages were identified to species level using the Vitek Bacillus biochemical card, the dichotomous key and table proposed by Berkeley et al. ((1984). In Methods in Microbiology, Vol. 16. Academic Press, London, p. 291), morphological and physiological tests and the API 20E miniaturized system. None of the tested systems was entirely satisfactory and the final identification was mainly done on the basis of cellular morphology and the table of test results. Our isolates belonged to the species: B. subtilis (37), B. megaterium (22), B. pumilus (5), B. circulans (3) and unidentified (2). Forty-five cultures (65.2%) were accurately identified with the dichotomous key. A similar figure for the Vitek Bacillus biochemical card was 36%. The results of the API 20E system were very reproducible, especially those of the Voges-Proskauer test. Most of the strains of B. megaterium were misidentified as B. subtilis with the dichotomous key. On the other hand, a high percentage of the cultures belonging to B. subtilis were misidentified as B. megaterium with the Vitek system. PMID- 22060679 TI - Muscle glycogen levels and blood metabolites in reindeer (Rangifer tarandus tarandus L.) after transport and lairage. AB - A total of 66 reindeer cows and calves were included in a study on the effects of supplementary feeding, transport and lairage on muscle glycogen content, ultimate pH and blood metabolite values. Thirty reindeer (10 not transported, 20 transported 800 km) received no supplementary feed (groups A-C), another 30 animals (10 not transported, 20 transported 1000 km) were given a supplementary reindeer feed mixture 2 months prior to slaughter (groups D-F) and six animals, which had been part of a feeding experiment, were fed for 5 months and slaughtered at the research unit. Glycogen determinations and pH measurements were made in m. longissimus, m. biceps femoris and m. triceps brachii. Blood samples were collected at slaughter and muscle samples were taken 30 min after slaughter. Ultimate pH was measured 30 hr post mortem. The glycogen content in the muscles of groups A-C was very low (100-200 mmol/kg). In groups D-G, the glycogen content was equivalent to normal beef muscle values (300-500 mmol/kg). The values of the blood metabolites urea and creatinine, both of which could indicate protein catabolism caused by stress, were significantly (p < 0.05) higher in animals not having received supplemental feed (groups A-C). Alkaline phosphatase values were significantly (p < 0.05) higher in supplemental fed animals (groups D-G), indicating that their nutritional status was good. Total protein values were significantly (p < 0.05) higher in groups A, D, E and F compared to the other groups. Lorry transport did not significantly (p > 0.05) reduce the muscle glycogen content. Lairage (groups C and F) showed no negative effect on the parameters examined. These results suggest that the animals' physical condition and nutritional status have a considerable effect on their ability to tolerate various stress factors, such as lorry transport and lairage. PMID- 22060680 TI - Effect of the RN gene on technological and sensory meat quality in crossbred pigs with Hampshire as terminal sire. AB - The effect of the dominant RN gene (Rendement Napole) was studied in Hampshire crosses (Hampshire sires * Swedish Landrace-Swedish Yorkshire dams). The present material comprised 107 entire male and 52 female pigs slaughtered at 106 kg live weight. Carriers and non-carriers of the RN gene were distinguished on the basis of the glycolytic potential (GP) in post-mortem longissimus muscle, or with the Napole yield (yield after curing and cooking). Compared with the glycolytic potential classification, Napole classification gave 16% misclassified samples. In comparison with non-carriers of the RN gene, gene carriers showed the following significant differences in m. longissimus dorsi meat quality traits: lower pH, higher surface and internal reflectance values, lower protein extractability, lower water-holding capacity, lower Napole yield and greater cooking loss. The high correlation (r = -0.73; p < 0.001) which was found between GP and Napole yield in the total material, was absent in muscle from individuals carrying the RN gene. In addition to the detrimental effect on meat quality, the RN gene also had beneficial effects. Thus RN carriers had a lower (p = 0.02) shear force value (Warner-Bratzler) and, at sensory testing, a stronger taste and smell and greater acidity (9-member untrained panel). No difference was found in sensory evaluated tenderness. PMID- 22060681 TI - Addition of lipase from Candida cylindracea to a traditional formulation of a dry fermented sausage. AB - The objective of this work was to study the manufacture of sausage containing a traditional starter culture (Lactobacillus plantarum and Staphylococcus carnosus) together with an enzyme lipase from Candida cylindracea as compared with that of a sausage with only starter. The acidity value showed more intense lipolysis in the sausage with lipase with this increase being especially important in the second week of drying. In spite of this, there was no significant (p > 0.05) increase in the oxidative rancidity processes in this sausage. The analysis of short chain fatty acids suggested the enzyme and starter together produced a greater amount of such acids than did the enzyme or the starter separately. Almost all free fatty acids showed significantly higher values in the sausage with lipase with the exception of linolenic acid. The addition of enzyme lipase produced a higher proportion of free saturated acids and a lower proportion of polyunsaturated acids during the drying of the sausage. PMID- 22060682 TI - The retail display life of steaks prepared from chill stored vacuum and carbon dioxide-packed sub-primal beef cuts. AB - Chilled striploins and cube rolls from ten Australian steers (grain-fed for 150 days) were trimmed of external fat and cut transversely into portions approximately 10 cm thick, each weighing between 750 and 1000 g. These 'retailer ready' cuts were each wrapped in drip saver pads and slid inside a plastic sleeve before being individually placed into a clear plastic high oxygen barrier film, metallized film or conventional vacuum bag. Cuts in clear plastic and metallized film packs were packaged in an oxygen-free saturated carbon dioxide atmosphere (CO(2)-CAP), those in vacuum bags were conventionally vacuum-packed. All packs were returned to the chiller for further cooling. After 24 hr, half the clear plastic and metallized CO(2)-CAP packs were carbon dioxide master-packed in groups of eight. Retailer-ready cuts in both clear plastic and metallized film single unit and master-packed CO(2)-CAP packs were air freighted to New Zealand and sea freighted to Japan for assessment. The control vacuum packs were all consigned to New Zealand. Assessments in both countries after 39-89 days storage at between 0 degrees C and -1.0 degrees C indicated that fat colour stability limited the retail display life of steaks cut from meat in these retailer-ready packs to approximately 48 hr. In this regard, meat from single unit CO(2)-CAP, master pack CO(2)-CAP and vacuum packs performed similarly. Lean meat colour and sensory attributes remained acceptable for up to 48 hr after displayed product was rejected because of grey-green fat discoloration. The microbiological status of retailer-ready cuts removed from CO(2)-CAP packs after 89 days chilled storage was superior to that of cuts from vacuum packs. Clear plastic and metallized film CO(2)-CAP packs performed comparably. PMID- 22060683 TI - Flavor and texture characteristics of low fat ground beef patties formulated with whey protein concentrate. AB - Low fat ground beef patties (10-11% fat), formulated with 10% water, 0.5% salt and 1-4% whey protein concentrate (WPC), were evaluated for cooking characteristics and compared with controls of higher fat content. A reduction in the fat level from 22 to 11% improved all cooking parameters with respect to better cooking yield (p < 0.01) and fat retention (p < 0.05), increased cooked moisture content (p < 0.05) as well as reduced shrinkage (p < 0.05). Texture profile analysis (TPA) showed an increase in chewiness for low fat samples over the high fat control, while hardness and springiness remained unaffected. Adding 10% water to the low fat meat did not change the cooking characteristics, except for a further increase in cooked moisture content (p < 0.05) and an increase in the value for springiness (p < 0.05). Addition of increasing levels of WPC with 10% water to low fat meat resulted in a linear increase (p < 0.05) in cooked yield with a linear decrease (p < 0.05) in shrinkage. The 4% WPC level produced the highest cooking yield (125% of the high fat control) and the least shrinkage (49% of the high fat control). Sensory analysis showed the 4% WPC level to be preferred over lower levels with respect to juiciness and overall acceptability. Addition of 0.3% of texture-modifying additives showed that calcium chloride and hydroxypropylmethylcellulose had a detrimental effect on yield and shrinkage, whereas the effect of tripolyphosphate (TPP) was positive (p < 0.05). Perception of juiciness and overall acceptability of formulated low fat products was significantly better (p < 0.05) with the addition of TPP (0.3%) and lactose (1.2%) to the WPC formulations. Fat levels (11, 18 and 22%) and lactose levels (0.24 and 1.2%) affected volatile components of the beef patties as measured by dynamic head space analysis. Ketones, i.e. 2-butanone, 2-pentanone and 3-hydroxy 2-butanone increased with an increase in fat content from 11 to 22% fat. Addition of WPC and lactose decreased the relative concentrations of pentane, hexane and heptane. The increase of lactose level in meat was accompanied by an increase in 4,4 diethyl-2-oxetanone and 2-methyl-butanal, two compounds that may originate from non-enzymatic browning of lactose. PMID- 22060684 TI - Influence of carcass weight on instrumental and sensory lamb meat quality in intensive production systems. AB - The influence of carcass weight (CW) on instrumental and sensory meat quality traits was studied in Rasa Aragonesa lamb carcasses. Forty-six intact male lamb carcasses were divided into three groups: 8.07 (S.D. 0.36) kg (A); 10.22 (S.D. 0.79) kg (B) and 13.42 (S.D. 1.36) kg (C). Results indicate that CW significantly influenced instrumental measurements in all the traits considered, except for waterholding capacity. The weight increase produced higher pH, haem pigment and redness (a (*)) and lower lightness. Shear values were higher (p <= 0.01) in group B. Sensory traits were not influenced by CW with the exception of juiciness. This parameter increased in the order A-B-C, and the subjective colour estimation was darker in groups B and C. The results show that it is possible to produce heavier or lighter lamb carcasses than traditional lamb (Ternasco de Aragon, group B), without significant losses in meat quality. This fact could give flexibility to a system permitting the slaughter weight to be adjusted to variations in seasonal prices. PMID- 22060685 TI - The display life of retail packaged pork chops after their storage in master packs under atmospheres of N(2), CO(2) or O(2) + CO(2). AB - Commercial, bone-in pork loins were divided into four portions. One portion of each loin was vacuum packaged, then stored at -1.5 degrees C. The other portions were each divided into three chops, which were retail packaged. The retail packs were master packaged under atmospheres of N(2), CO(2) or O(2) + CO(2) (2:1, v/v), then stored at 2 degrees C. The pork was assessed after storage for up to 42 days. At each assessment, a vacuum pack and a master pack of each type, each containing product from the same loin, were withdrawn from storage. The vacuum packaged portion was cut into three chops, which were retail packaged. The chops from all packagings were displayed in a retail cabinet which maintained average air temperatures between 3 and 6 degrees C. The chops were assessed twice daily until they were judged to be of undesirable appearance. After storage for 1 or 2 days, the chops from all master packs appeared less desirable than the freshly cut chops. After all longer storage times, chops from N(2) and CO(2) atmospheres appeared as desirable as freshly cut chops, as did chops from O(2) + CO(2) that were stored for up to 16 days. However, chops stored under O(2) + CO(2) for 21 days appeared undesirable. Chops stored under N(2) or O(2) + CO(2) developed spoilage odours, after storage for 28 or 21 days, respectively. Bacteria were more numerous on the fat than on the muscle tissue. The numbers of bacteria were 10(7) cfu cm(-2) on the fat surfaces of chops stored under vacuum or N(2) for 42 days. The numbers of bacteria were 10(6) cfu cm(-2) on the fat surfaces of chops stored under CO(2) for 42 days or under O(2) + CO(2) for 21 days. At those times, only lactobacilli were isolated from chops stored under CO(2), but small or large fractions of enterobacteria were present in the flora on chops stored under vacuum or N(2), respectively, while the flora on chops stored under O(2) + CO(2) contained large fractions of Brochothrix thermosphacta and Gram negative, strictly aerobic, spoilage bacteria. After all storage times, chops cut from vacuum packaged portions remained of desirable appearance when displayed for 48 hr or longer. Chops stored under N(2) or CO(2) for between 2 and 35 days, or under O(2) + CO(2) for between 4 and 12 days, retained a desirable appearance during display for the same times as the freshly cut chops. Off-odours were apparent in chops after their display following storage under vacuum or CO(2) for 21 days, or under N(2) or O(2) + CO(2) for 12 days. The numbers of bacteria on the fat surfaces of chops spoiled by off-odours were >= 10(5) cfu cm(-2). The flora on chops removed from display were generally enriched for B. thermosphacta, enterobacteria and/or Gram negative aerobes as compared with the flora on the chops when they were removed from the storage packs. Those data indicate that the storage life of master packaged, display ready pork will probably be severely limited by the poor hygienic condition of commercial products, to little more than 1 week for product stored under N(2) or O(2) + CO(2) or < 3 weeks for product stored under CO(2). PMID- 22060686 TI - The relationship between sensory time-intensity, physiological electromyography and instrumental texture profile analysis measurements of beef tenderness. AB - The relationship between the perception of tenderness, chewing activity and instrumental compression was explored by time-intensity, electromyography and instrumental texture profile analysis (ITPA). Bovine m. longissimus dorsi from five treatments were evaluated by seven individuals. Time-intensity results showed that the Decrease Area and Area Under the Curve provided the most information regarding sample differences, with the former providing the best sample discrimination. Electromyographic results of mastication rate demonstrated the number of chews required to reach maximum force to chew. The results suggest a need to re-examine the effects of early mastication vs the late mastication effects for the measurement of meat tenderness. PMID- 22060687 TI - Is there a protease that preferentially cleaves the M-line in partially dehydrated muscle? AB - When a partially dehydrated muscle fibre bundle (PDM, 65% H(2)O, pH 5.5, at 4 degrees C) was treated with a supernatant fraction (M-line-cleaving fraction: MCF) of muscle homogenate for 5 hr, the M-lines disappeared. MCF was extracted from rabbit skeletal muscles by homogenization with 15 mM HCl containing 0.5 M NaCl (pH 3.7), fractionated with 25-65% (NH(4))(2)SO(4) and clarified by Sephadex G-75. Rabbit psoas PDM was obtained with an osmotic dehydration sheet and glycerinated. One end of the bisected fibre bundle was incubated with 10 mM Na acetate (pH 5.5), 1 mM EDTA, 5 mM beta-mercaptoethanol (beta-MCE), 150 mM KCl, 10 mM NaN(3) with MCF at 25 degrees C for 5 hr, the muscle being stretched and relaxed several times. The other end was incubated in the same solution, except that MCF was omitted (control). Electron microscopy showed the myofibrils broken down at the M-line in the presence of MCF. The myofilaments were closely packed near the Z-line and flared out at both ends near the centre of the sarcomere (bow tie shape). Thus, the Z-line is not the only target of proteases and structural decomposition can also occur at the M-line under specific conditions. An M-line cleaving protease may exist in the MCF muscle extract. PMID- 22060688 TI - Post-mortem pH decline in different ostrich muscles. AB - Post-mortem glycolysis, as described by muscle pH decline, was investigated in several ostrich muscles. While the gastrocnemius pars interna, femorotibialis medius, iliotibialis lateralis and iliofemoralis showed the normal descending pH decline pattern, the ambiens as well as the iliofibularis showed a very rapid pH decline until 2 hr post mortem whereafter pH increased. PMID- 22060689 TI - Yeast populations on Spanish fermented sausages. AB - Yeast populations on 24 lots of Spanish fermented sausages, made by four factories (F1, F2 and F4, artisanal; F3, industrial) were investigated throughout manufacture and the influence of different variables evaluated. In addition, 41 yeast strains were identified at the species level using two miniaturised systems: ATB32C (API System) and Vitek Yeast Biochemical Card (Vitek YBC). Levels of yeasts found in the sausage mixture (mean counts around 4 log units/g) were similar to those described by other authors. In sausages from factories F1 and F2, a further increase was noted, reaching 5.5 log units/g after fermentation. Counts subsequently decreased to 3.6 and 5 log units/g, respectively. In sausages from factories F3 and F4, decreasing counts were observed from the beginning, particularly in sausages from F3, where yeasts were almost absent in the finished product. Type of manufacture and sausage diameter, were the variables most influencing yeast counts. Debaryomyces hansenii (teleomorph of C. famata) was the dominant species, being found at all stages of manufacture. Trichosporon ovoides (formerly T. beigelii), Yarrowia lipolytica (perfect form of C. lipolytica), C. intermedia/curvata, C. parapsilosis, C. zeylanoides and Citeromyces matritensis (teleomorph of C. globosa) were also present. Direct identification was possible only with 50% of the total of strains investigated, although a higher number of strains was identified using the API than the Vitek YBC system. PMID- 22060690 TI - Analysis of volatile components and the sensory characteristics of irradiated raw pork. AB - Longissimus dorsi muscle strips, approximately 20 mm long, 40 mm wide, and 5 mm thick (4 g), of pig were randomly placed in a single layer into labeled bags (four strips per bag) and packaged either aerobically or under vacuum. Samples in the bags were irradiated at 0, 5, or 10 kGy and stored at 4 degrees C for 5 days. Lipid oxidation, the amount and identity of volatile components and sensory characteristics of raw pork strips were determined at 0 and 5 days of storage. Irradiated muscle strips produced more 2-thiobarbituric acid reactive substances (TBARS) than nonirradiated only in aerobic packaging during storage. Irradiation had no effect on the production of volatiles related to lipid oxidation, but produced a few sulfur-containing compounds not found in nonirradiated meat. This indicates that the major contributor of off-odor in irradiated meat is not lipid oxidation, but radiolytic breakdown of sulfur-containing amino acids. Many of the irradiation-dependent volatiles reduced to 50 to 25% levels during the 5-days storage under aerobic conditions. Irradiated muscle strips produced stronger irradiation odor than nonirradiated, but no irradiation dose or storage effect was found. Irradiation had no negative effect on the acceptance of meat, and approximately 70% of sensory panels characterized irradiation odor as barbecued corn-like odor. PMID- 22060691 TI - Evaluation of electrical stunning in commercial rabbits effect on brain function. AB - Effect of electrical stunning on brain function in commercial rabbits was evaluated in electrophysiological studies. In addition to measuring duration of spontaneous physical activity and times to signs of recovery, electrocorticogram (ECOG) recordings and evoked responses were analysed following electrical stunning with 100 V for 1 s in eight rabbits. Epileptiform and other types of activity indicating insensibility were observed in the ECOG. Evoked responses were absent from 24 to 204 s following stunning. Application of a minimum current of 140 mA followed by prompt sticking should prevent welfare problems at stunning and slaughter in rabbits. PMID- 22060692 TI - Preslaughter resting and hot-fat trimming effects on the incidence of pale, soft and exudative (PSE) pork and ham processing characteristics. AB - Effects of preslaughter rest (0, 1, 2 or 3 h) and hot-fat trimming (HFT, one side) on muscle quality characteristics of hams and loins were tested with 120 pigs. Center-cut loins from each carcass side were vacuum packaged and stored for 7 or 14 days at 2 degrees C. Pigs not rested before slaughter had a skin temperature 3 degrees C higher and ham muscle temperatures 1 degrees C higher than pigs rested 1-3 h (P<0.05). Three hour muscle pH was highest if pigs were rested for 1 h. HFT significantly accelerated carcass chilling rate, but did not affect rate of muscle pH decline. After 14 days of aging, pigs not rested had lower sensory panel ratings for juiciness, tenderness, flavor and overall mouthfeel of loin chops than pigs rested 1 or 2 h. Percentage bound water of hams was highest (P<0.05) if pigs rested 1 or 2 h rather than a shorter or longer times. Pigs should be rested 1 h before slaughter and HFT carried out to allow more rapid carcass chilling and improve muscle quality. PMID- 22060693 TI - Testing for the RN(-) gene in retail pork chops. AB - A random sample of pork chops were purchased from local retail outlets to determine if the frequency of the RN(-) phenotype could be roughly estimated by GP measurements in fresh raw pork products or by genotyping for the nearest DNA microsatellite markers. Glycolytic potential (GP) is the estimated sum of glycogen, the intermediate metabolites of glycogenolysis, and the end product, lactate. GP has been used to identify a genetic mutation known as the RN(-) or Hampshire gene. Currently, there is no genetic test for the RN(-) allele and flanking DNA microsatellite markers were not useful at predicting the RN(-) phenotype in the random samples. Excessively high GP was found in 25% of the samples which correlated with a significant (P>0.05) drop in pH (5.8 to 5.7), a paler (L* value; 54.1 to 57.5) more yellowish (b* value; 9.6 to 11.6) color, and an increased cooking loss (9 to 18%), typical of the RN(-) phenotype. A genetic test for skin colour in swine proved that the majority (79%) of high GP pork sampled were from phenotypically white pigs. Analysis of glucose levels in post rigor samples may be useful in progeny testing for the RN gene until a true genetic marker can be identified. PMID- 22060694 TI - Modelling the effect of sarcomere length on collagen thermal shortening in cooked meat: consequence on meat toughness. AB - Normal and contracted pieces of Semimembranosus and Longissimus Dorsi muscles from cull cows were cooked for 90 min at temperatures up to 80 degrees C. For both muscles, at 50 degrees C the normal samples have higher breaking stress than contracted samples. The breaking stress of normal samples decreases at 55 degrees C. This decrease is not observed for contracted samples. The contracted samples become the tougher above 60 degrees C. Drip and cooking losses are the highest in contracted samples. Sarcomere length decreases above 60 degrees C whatever the raw sarcomere length. The amplitude of thermal shortening of perimysium collagen fibres in cooked meat has been calculated. This theoretical model takes into account the changes in the waviness of collagen fibres associated with changes in raw sarcomere length and the geometrical changes of fibre bundles due to drip, cooking losses and cooking shortening. The calculations lead to the conclusion that thermal shortening of collagen fibres at 60 degrees C is lower in contracted samples than in normal samples. As the final modulus of collagen fibres decreases when their thermal shortening increases, this can explain part of the differences observed between the toughness of normal and contracted cooked meats. In particular, it can explain why contracted cooked meat becomes tougher than normal meat just above 60 degrees C and why there is a decrease in normal meat toughness between 55 and 60 degrees C. This work therefore emphasises the role of collagen in toughening associated with cold shortening. PMID- 22060695 TI - An international study on the importance of androstenone and skatole for boar taint: I. Presentation of the programme and measurement of boar taint compounds with different analytical procedures. AB - An international study, involving 11 participants in 7 European countries, was conducted to provide scientific evidence for an objective measurement of boar taint in entire male pigs and its possible variation between countries. The specific objectives were to determine the respective contributions of androstenone and skatole to boar taint and their possible variations according to production systems and consumer populations. Over 4000 entire male pigs and 200 gilts were raised and slaughtered in 6 countries. Meat samples were taken from the loin and backfat samples were used for the rapid measurement of androstenone and skatole. A sub-population of 377 entire males and 42 gilts was then selected in such a way as to represent all combinations of skatole and androstenone levels. Androstenone and skatole levels in the selected samples were checked, using established reference methods. Meat samples from the selected animals were used for sensory evaluation by trained panels and for consumer surveys in 7 European countries. The present paper gives a general presentation of the programme and reports the main characteristics of the samples. Three companion papers present the results of the evaluation by trained sensory panels [Dijksterhuis, G., Engel, B., Walstra, P., Font i Furnols, M., Agerhem, H., Fisher, K., Oliver, M. A., Claudi-Magnussen, C., Siret, F., Beague, M. P., Homer, D. B., & Bonneau, M. (2000). An international study on the importance of androstenone and skatole for boar taint: II. Sensory evaluation by trained panels in seven European countries. Meat Science54, 261-269], the results of the consumer surveys [Matthews, K. R., Homer, D. B., Punter, P., Beague, M. P., Gispert, M., Kemspter, A. J., Agerhem, H., Claudi-Magnussen, C., Fischer, K., Siret, F., Leask, H., Font i Furnols, M., & Bonneau, M. (2000). An international study on the importance of androstenone and skatole for boar taint: III. Consumer survey in seven European countries. Meat Science, 54, 271-283] and the main conclusions and recommendations [Bonneau, M., Walstra, P., Claudi-Magnussen, C., Kempster, A. J., Tornberg, E., Fischer, K., Diestre, A., Siret, F., Chevillon, P., Claus, R., Dijksterhuis, G., Punter, P., Matthews, K. R., Agerhem, H., Beague, M. P., Oliver, M. A., Gispert, M., Weiler, U., von Seth, G., Leask, H., Font i Furnols, M., Homer, D. B., & Cook, G. L. (2000). An international study on the importance of androstenone and skatole for boar taint: IV. Simulation studies on consumer dissatisfaction with entire male pork and the effect of sorting out carcasses on the slaughter line, main conclusions and recommendations. Meat Science, 54, 285-295]. Seasonal effects and differences between countries in skatole and androstenone levels are presented elsewhere [Walstra, P., Claudi Magnussen, C., Chevillon, P., von-Seth, G., Diestre, A., Matthews, K. R., Homer, D. B., & Bonneau, M. (in press). An international study on the importance of androstenone and skatole for boar taint: Levels of androstenone and skatole according to country and season. Livestock Production Science]. A supplementary paper considers the effects of human sensitivity to androstenone and skatole on the consumer acceptance of entire male pork [Weiler, U., Font i Furnols, M., Fischer, K., Kemmer, H., Oliver, M. A., Gispert, M., Dobrowolski, A., & Claus, R. (in press). Influence of differences in sensitivity of Spanish and German consumers to perceive androstenone on the acceptance of boar meat differing in skatole and androstenone concentrations. Meat Science]. A study of possible other compounds contributing to boar taint was also carried out within this programme. PMID- 22060696 TI - An international study on the importance of androstenone and skatole for boar taint: II. Sensory evaluation by trained panels in seven European countries. AB - The aim of the present study (part of an EU AIR programme on boar taint) was to make objective the perception of boar taint in entire male pork, and to relate the perception to skatole and androstenone levels. Trained analytical sensory panels in seven European countries assessed pig meat with known levels of androstenone and skatole. The panels performed a sensory profiling using the attributes pig, urine, manure/stable, naphthalene/mothballs, rancid, sweet, sweat and abnormal, both for odour and flavour in separate sessions. It turned out to be difficult to harmonise sensory methodology for seven sensory panels throughout the EU, especially with respect to the exact level of training the panellists received. Sensory panels in general were able to differentiate between the two compounds and between different levels of the compounds, though substantial differences between the panels in the different countries existed. Androstenone was found to relate mostly to the urine attribute, while skatole related mostly to manure and, to a lesser extent, to naphthalene. PMID- 22060697 TI - An international study on the importance of androstenone and skatole for boar taint: III. Consumer survey in seven European countries. AB - There has long been debate over the relative importance for consumer acceptability of androstenone and skatole. The objective of this study was to investigate consumer reaction to pig meat of varying levels of androstenone and skatole in seven member states of the European Union. Over 4000 entire male pigs (and 233 gilts as a control) were produced in six European countries, and a sub sample of 420 were selected to represent a range of androstenone and skatole levels. Loin samples from these pigs were distributed to the seven participating countries. Samples were prepared and cooked according to standardised procedures in each of the countries and presented to pork consumers. Each consumer rated samples from five pigs for liking of flavour and liking of odour. Although there were significant differences between country panels in their liking of meat from entire males generally, there was a greater degree of dislike as both androstenone and skatole increased. This reaction was stronger for skatole than androstenone and consumers reacted more negatively in terms of odour than flavour. PMID- 22060698 TI - An international study on the importance of androstenone and skatole for boar taint: IV. Simulation studies on consumer dissatisfaction with entire male pork and the effect of sorting carcasses on the slaughter line, main conclusions and recommendations. AB - An international study has been conducted in order to determine the respective contributions of androstenone and skatole to boar taint and their possible variations according to production systems and consumer populations. The presentation of the study and the main results concerning skatole and androstenone levels and data from sensory evaluation or consumer surveys are reported in companion papers. The present paper summarises the main conclusions of the study and gives tentative recommendations. A simulation study was conducted, based on the skatole and androstenone levels currently observed in European populations of entire male pigs and on the results of the consumer surveys. The first part of the simulation study demonstrated that, overall, 6.5% (odour) and 3.0% (flavour) more consumers were dissatisfied with entire male than with gilt pork. The differences were, however, very variable according to countries. Consumer dissatisfaction for the odour of entire male pork was mostly associated with high skatole levels, while androstenone had little influence on it. On the other hand, androstenone and skatole had similar contributions to the level of dissatisfaction for flavour. From the present study it is not possible to determine clear cut-off levels for androstenone/skatole. The regression equations presented in [Matthews, K. R., Homer, D. B., Punter, P., Beague, M. P., Gispert, M., Siret, F., Leask, H., Fonti i Furnols, M., & Bonneau, M. (2000). An international study on the importance of androstenone, skatole for boar taint: III. Consumer survey in seven European countries. Meat Science, 54, 271-283] provide a basis for decision making. However, due to methodological limitations, the results may underestimate consumer reaction to entire male pork. The second part of the simulation study demonstrated that sorting carcasses on the basis of androstenone/skatole would reduce, but not eliminate, differences in consumer dissatisfaction between entire male and gilt pork. For odour, taking androstenone into account did not improve the efficiency obtained from sorting using skatole only. For flavour, sorting using both compounds was more efficient than sorting using skatole only. Sorting out 15% of the entire males, on the basis of skatole only, would result in a difference in the proportion of dissatisfied consumers of 4.2% (odour) or 2.0% (flavour) between entire male and gilt pork. The results of the last part of the simulation study demonstrated that decreasing skatole in entire male pig populations, to levels as low as 0.10 ppm, would still result in a difference in the proportion of dissatisfied consumers of 3.2% (odour) or 1.6% (flavour). To reduce this difference further, the levels of both compounds would have to be reduced still further. The lowest difference that can be achieved is 2.3% (odour) or 0.4% (flavour). The conclusions of the present study may differ according to whether immediate commercial applications or long-term goals are considered. On the basis of the skatole and androstenone levels currently observed in entire male pig populations, sorting out procedures based on skatole is the easiest way to rapidly achieve a significant decrease in consumer dissatisfaction with entire male pork. In most countries, however, this will not be sufficient to obtain the same level of acceptability as with gilts. In the long term, a sharp reduction in both skatole and androstenone would have to be achieved in entire male pig populations to obtain low differences in acceptability between entire male and gilt pork. PMID- 22060699 TI - Influence of differences in sensitivity of Spanish and German consumers to perceive androstenone on the acceptance of boar meat differing in skatole and androstenone concentrations. AB - The reactions of German (n=472) and Spanish (n=480) consumers of the European boar taint study to boar meat were evaluated according to their androstenone sensitivity. Consumers were checked with pure substance for their androstenone sensitivity. Eighteen per cent of the German and 31% of the Spanish participants were highly sensitive to androstenone, with a significantly higher proportion of women. For insensitive/mildly sensitive consumers, skatole level was the main determinant for the rating of flavour and odour of pork. For highly sensitive consumers, androstenone significantly influenced the rating of odour (Spain and Germany) and flavour (Germany) and is the predominant problem for that group, due to the high percentage of carcasses with high androstenone levels. PMID- 22060701 TI - Preface. PMID- 22060700 TI - Development of a quality monitoring program for platelet components: a report of the first four years' experience at Canadian Blood Services. AB - BACKGROUND: A quality monitoring program (QMP) for platelet concentrates (PCs) was implemented at Canadian Blood Services (CBS) to improve standards and to better understand platelet (PLT) products by supplementing routine quality control (QC). STUDY DESIGN AND METHODS: Annual surveys of PCs from CBS production sites were conducted, with four completed to date (QMP Cycles 1-4) spanning two different PC production methods: PLT-rich plasma (PRP) and buffy coat (BC). Randomly selected PCs were sent to a central laboratory and tested 1 day after expiry. An expanded panel of tests including CD62P expression by flow cytometry, mean PLT volume, PLT count and morphology, extent of shape change, and PLT metabolic parameters, were applied. RESULTS: QMP data on the implementation of the BC production method across CBS indicated that BC PCs have less variable in vitro quality measures than PRP PCs. For the QC parameters pH and PLT count per unit, the range of mean values from each site for QMP 3 and 4 fell well within the range defined by regulatory standards, a first step in defining quality benchmarks for PCs. Of the extended panel of quality parameters, CD62P expression was the most sensitive indicator of change and identified an issue with the implementation of the BC PC production method at one site, which was subsequently remedied. CONCLUSION: A QMP was found to be useful to monitor production processes across sites and highlights best practice approaches while deepening understanding of the quality of PLT products at CBS. PMID- 22060702 TI - Some recent advances and future priorities in research for the meat industry. AB - The meat industry is undergoing a period of very mixed fortunes with beef in particular losing market share; however, longer term forecasts are good for all meat species with demand growth coming mainly from developing countries. This review deals in particular with the main problems that are responsible for the decline of beef as a consumer product in developed markets. These are the meat safety crisis and the unreliability of meat eating quality, especially tenderness. The review suggests that recent research has defined and clarified these problems but they have not been elucidated to the extent that is needed for product assurance. Hence, meat safety and consistent quality are two of the core issues to be addressed in future research. The third core issue is product development which is very active in the most competitive sectors of the food industry and is weak in the red meat sector. PMID- 22060703 TI - Proteolysis and lipolysis in flavour development of dry-cured meat products. AB - Numerous proteolytic and lipolytic reactions are involved in the generation of flavour and/ or flavour precursors in meat and meat products. Most of these reactions are known to be due to endo-/exo-peptidases and lipases, respectively. The origin of these enzymes may be either from muscle and/or from microorganisms, although their relative relevance for a given meat product strongly depends on the manufacture and distribution. In this paper, the postmortem proteolysis and lipolysis is described with particular reference to dry-cured ham, a typical meat product naturally ripened by endogenous enzymes. PMID- 22060704 TI - Bacterial role in flavour development. AB - The role of bacteria in the production of non volatile and volatile compounds involved in the fermented meat flavour is discussed. Lactic acid bacteria produce D-lactic and acetic acids which may give a sour note. By reducing the pH, they also modulate the other bio-chemical bacterial activities. In muscle tissue proteins are degraded into peptides and lipids into fatty acids mainly by endogenous enzymes. In fermented meat products with a high pH lipases from very lipolytic species of Staphylococcus could increase lipolysis. Bacteria could also play a role in the production and degradation of free amino acids. Staphylococcus and to a lesser extent, lactic acid bacteria could participate in the production of methyl-branched aldehydes and their corresponding alcohols and acids from branchedchain amino acids. By their nitrate reductase and catalase Staphylococcus species limit fatty acid oxidation and aldehyde production. Staphylococcus could contribute to the ester content as they can produce or hydrolyse esters in vitro. PMID- 22060705 TI - New developments in meat starter cultures. AB - Meat starter cultures containing one or more strains of lactic acid bacteria,Actinobacteria, staphylococci,Halomonas elongata, Aeromonas spec., and moulds or yeasts are widely in practical use. The progress in microbial systematic has led to changes in the taxonomy of familiar bacterial species which are described. Studies of flavour genesis led to the identification of the contribution of the enzyme activities endogenously present in the meat matrix as well as of those exerted by the starter cultures. Characteristic compounds of the aroma of fermented meat products originating from the starter organisms were also described. New knowledge was accumulated on the physiology and genetics of starter bacteria and some insight has been gained in the regulation of the expression of genes encoding important properties such as bacteriocin production or catalase activity. The applicability of gene technology to starter strains has been shown and strains have been constructed that have the potential to further improve the technological and hygienic suitability of starter cultures. New applications of the micro-organisms as protective or probiotic cultures have been developed for application in meat science. PMID- 22060706 TI - Bacteriocinogenic lactic acid bacteria for the biopreservation of meat and meat products. AB - The consumer demands for less preserved foods and the development of new food systems to fulfil these demands, urges new hurdles for pathogen growth. The strategies for pathogen reduction are not selective for pathogenic microorganism and therefore the non-spoilage microorganisms may become also inactivated, from this situation a question of concern about a freer way for pathogen growth is arised. Biopreservation refers to the extended storage life and enhanced safety of foods using their natural or controlled microflora and (or) their antibacterial products. In meats, lactic acid bacteria (LAB) constitute a part of the initial microflora which develops easily after meat is processed. LAB growth in meat can cause microbial interference to spoilage and pathogenic bacteria through several mechanisms, specially bacteriocins. The paper deals with the description of meat-borne bacteriocins and their application in meat and meat products either to extend the shelf life or to inhibit meat pathogens. The application of bacteriocinogenic LAB together with new technological hurdles is discussed. PMID- 22060707 TI - Factors affecting the emergence of pathogens on foods. AB - Recent times have seen the emergence of a number of new or emerging pathogens. Research is needed to establish the mechanisms underlying their emergence in foods, and their interactions with traditional food production processes. The paper reviews the general relationships between environmental stresses and pathogen emergence. Non genetic mechanisms of pathogen adaptation to stress are considered, focusing on acid resistance as an example of particular importance to pathogen survival in food and the human host. The influence of environmental factors in genetic adaptation in stationary phase cells are considered in relation to the development of non-directed antibiotic resistance, i.e. development of resistance when antibiotics are not present in the environment. The paper examines the molecular mechanisms underlying such genetic processes and their enhancement during environmental stress. The implications of these mechanisms for food safety and pathogen emergence are discussed. PMID- 22060708 TI - Dry fermented sausages. AB - Two major aspects of fermented sausages are discussed in the article. After a brief history of enterohemorrhagicEscherichia coli with special regard to fermented meat products the basic experimental designs and results are tackled on the basis of which safety issue in this respect is thoroughly discussed. The results show a rather limited opportunity for meeting food safety requirements with short or medium time ripened raw fermented sausages while traditionally, long ripened sausages are in a much better position. Fermented meat products as probiotics are also discussed. After evolving the EHEC outbreaks caused by fermented sausages the possibilities for finding reliable methods and products have been narrowed and more research is needed to find optimum solution. PMID- 22060709 TI - Sustained utilization of the Iberian pig breed. AB - The Iberian pig is one of the scarce non-improved swine breeds which survives the modern techniques of pig production based on improved genotypes. This is attributed both to its perfect adaptation to the Mediterranean natural ecosystem and the high quality of its products. The production of meat products from Iberian pigs has very little in common with that of meat products obtained from selected pigs raised under intensive conditions, and it constitutes an example of the preparation of high quality meat products, comparable to the most exquisite food products in the world. The production of Iberian pig is deeply bound to the Mediterranean ecosystem. It is a rare example in the world swine production where the pig contributes so decisively to the preservation of the ecosystem. The aim of this review is to describe in detail the traditional feeding of the Iberian pigs in La Dehesa and to discuss some aspects of the use of alternatives to this production system. Some of the experience in the formulation of compounds feeds for Iberian pigs and in the processing of meat products could be useful in the feeding of other pig genotypes and in different meat processing strategies. PMID- 22060710 TI - Rapid microbiological methods in meat and meat products. AB - Modern analytical techniques have to provide accurate results in time to permit forward approaches for controlling the microbiological quality of foods. Although the classical microbiological procedures of counting and identification of micro organisms have been automated, several techniques with quite different principles are now used. The quantification of the microbial load of meat samples can be done in 4-24 hr with methods involving the growth of micro-organisms in liquid media (impedance and turbidimetric methods) and in less than 2 hr with methods counting stained microbial cells or detecting components of microbial cells. Rapid detection of undesirable (pathogens or spoilers) micro-organisms in meat samples can be done with immunological and DNA-based methods. The main techniques which can be used for the microbiological quantification and identification in the meat industries, as well as their applications are reviewed. Possibilities for rapid typing of bacterial isolates are also presented. Finally, some future trends in the microbiological analysis of foods are discussed. PMID- 22060711 TI - Quality Assurance schemes. AB - This paper considers the consumer's changing definition of quality in relation to meat and the current development of Quality Assurance (QA) schemes to ensure that certain quality standards are met. The key ingredients of QA schemes are food safety, animal welfare and sensory aspects (meat quality) although the latter is not a major feature of many schemes at present. For each of these components, points in the production-processing chain where problems can arise should be identified and control procedures introduced. Monitoring is required to check the effectiveness of these. This approach is based on HACCP principles although best practice rules are the basis of most current QA schemes. The paper identifies key points on the farm and in the abattoir where food safety, animal welfare and meat quality can be compromised and shows how best practice procedures are introduced to reliably raise standards. There is some concern about the credibility of some QA schemes in relation to the standards set, the strictness of inspection and especially the impartiality of auditing procedures. This may be ensured in schemes within Europe which comply with EN 45011 standards. The move towards more tightly regulated QA schemes to raise consumer confidence could benefit some traditional products and organic meat production schemes which already operate with strict specifications. PMID- 22060712 TI - Neurophysiology and assessment of welfare. AB - Concern for animal welfare is a major consideration in meat production and is based upon the belief that animals can suffer. Welfare may be considered in terms of the subjective experiences of animals; preference testing is often used in this approach. Neurophysiology has provided insight into the biological basis of emotions and into the mechanisms of learning and memory, which are important to interpret the results of preference tests. Welfare may also be defined in terms of the biological functioning of the animals; physiological measures of stress such as plasma levels of glucocorticoids, catecholamines, prolactin and endorphins, as well as heart rate and brain levels of neurotransmitters are then used to assess welfare. Individual differences in the stress response are important in welfare issues. Slaughter poses particular problems and neurophysiology has provided objective criteria to assess the effectiveness of electrical stunning. It is concluded that neurophysiology has made important contributions to assess and improve animal welfare. PMID- 22060713 TI - Muscle fibre type and meat quality. AB - Muscle morphology and fibre type composition are briefly reviewed in relation to colour stability and tenderness in beef, and water holding capacity, colour and eating quality in pork. A large inter-muscle and inter-animal variation exists in meat quality, which is often related to metabolic and contractile properties as determined by their muscle fibre type distribution. Characteristics of different muscles may be modified in living animals by environmental conditions and genetic selection. Selection experiments based on biochemical and histochemical characteristics determined in biopsies or otherwise, and study of correlated selection responses, may lead to the development and applications of (new) muscle traits in future breeding programmes. PMID- 22060714 TI - Recent methods for predicting quality of whole meat. AB - The world of meat faces a permanent need for new methods of meat quality evaluation. Researchers want improved techniques to deepen their understanding of meat features. Expectations of consumers for meat quality grow constantly, which induces the necessity of quality control at the levels of slaughtering, meat cutting, and distribution. This article is focused on techniques intended to predict technological and sensory qualities from measurements carried out on fresh intact meat. pH has been measured for a long time, but its on-line determination still progresses through automation. In the laboratory, NMR provides new insights on WHC mechanisms. Image processing has considerably improved the assessment of meat appearance. Developments of techniques for prediction of toughness are in progress, either directly, through ultrasonic analysis or NIR reflectance, or indirectly, through determination of connective tissue content by fluorescence probes. Control of authenticity benefits from the last developments of molecular biology and analytical chemistry. However, implementation of methods for meat quality evaluation has been very limited in the industry. The reasons for that situation are analyzed. Among the techniques recently described, the most promising for large-scale meat quality evaluation are considered to be ultrasonic analysis, image processing and NIR spectroscopy. PMID- 22060715 TI - The role of major genes and DNA technology in selection for meat quality in pigs. AB - The aim of this paper is to discuss the role of major genes and DNA technology in selection for meat quality in modern breeding schemes. An overview of major genes, including genes that affect water-binding, colour, marbling, boar taint and tenderness, is given. Two different approaches for the development of DNA tests as selection tools are described: (1) localization of relevant genes on the genome map using DNA markers, and (2) research on mutations in targeted functional genes (candidate genes). It is concluded that major genes for meat quality provide excellent opportunities, not only for increasing the level of meat quality, but also for decreasing variability. Furthermore, major genes can be exploited for differentiation for specific markets. It is stressed that phenotypic data on culled nucleus animals provide an important basis for the development of DNA tests for selection for meat quality. More fundamental research is recommended to understand the interactions of genes with each other and with environmental factors. PMID- 22060716 TI - Use of entire males for pig meat in the European Union. AB - The aim of the present paper is to review the present knowledge concerning the possible use of entire male pigs for meat production, with particular emphasis on the current situation in EU countries. Raising entire male pigs has a number of advantages including lower production costs, leaner carcass, reduction of the output of pollutants in the manure and improved welfare of the animals. However, it has also a number of drawbacks, most of them concerning meat quality, with boar taint being the most serious problem. A recent international study involving 7 EU countries has shown that a higher proportion of consumers is dissatisfied with entire male than with gilt pork (31.9 vs 26.0% for odour; 21.5 vs 18.5% for flavour). However, the perception of boar taint differs widely between countries. Skatole, a compound with intense faecal odour, and androstenone, a steroid with intense urinary odour, are held as responsible for boar taint. The above mentioned international study demonstrated that skatole has a higher contribution than androstenone for consumer perception of unpleasant odours, while both compounds have similar contributions to unpleasant flavours. In the current situation, a high proportion of the entire male pigs reared in EU countries exhibit skatole/androstenone levels that result in a significant increase in consumer dissatisfaction, comparatively to gilt pork. Fat skatole levels are mostly dependent on feeding and rearing factors, while fat androstenone content is mostly determined by genetic factors. Besides the economic advantages associated with the production of entire males, the animal welfare issue may result some day in EU regulations prohibiting the castration of male piglets as it is currently performed. This would lead to a degradation of meat quality unless something is done to control the boar taint problem. An integrated approach should be considered with actions taken at the three levels of animal production, slaughter and processing. On the short range, immunocastration may offer a viable way for a drastic reduction of the incidence of boar taint in entire male pig populations. On the long range, selection against skatole/androstenone may be cheaper and more readily acceptable. Artificial noses and related techniques offer interesting possibilities for the assessment of boar taint on the slaughter line, however, further developments are needed in order to determine whether they can be used in industrial conditions. Tainted meat can be used through processing, however specific studies have to be conducted for each of the many products that can be processed from pig meat. PMID- 22060717 TI - Electronic nose and artificial neural network. AB - Gas sensor array technology combined with multivariate data processing methods as artificial neural network has been demonstrated to have a promising potential for rapid nondestructive analysis of odour and flavour in foods. It may be applicable in quality control of raw material, food processing or products. This technique cannot completely replace reference methods like the use of sensory panels as the technique requires a frequent calibration against some valid reference method. As with all new techniques there remain some basic problems to be solved concerning sample handling and instrumental performance. The emerging research activity in the development of chemical sensors including hardware and software combined with applied research makes it realistic to expect applications with this technique implemented on-line in the food industry in near future. In particular, promising applications on meat seem to be within the field of spoilage, off-flavour, sensory analysis and fermentation processes. PMID- 22060718 TI - Consumer perceptions of meat. Understanding these results through descriptive analysis. AB - Consumer perceptions of meals are investigated through qualitative and quantitative consumer studies. Qualitative studies add value and meaningful information to quantitative studies of meat. Among the important issues to consider in designing a quantitative consumer test for meats is the selection of terms to be used in a questionnaire. Additional terms besides tenderness, juiciness and flavor liking should be used to fully investigate consumer perceptions of meats. The limitations of consumer language is discussed. These limitations may be overcome through consumer-descriptive studies. These studies combine descriptive/sensory laboratory data with consumer information to decode consumer responses. The applications of this approach are: to achieve a more thorough interpretation and understanding of consumer responses, to provide more specific product guidance, to enable the prediction of consumer responses based on internal data (e.g. descriptive, instrumental), and to study different consumer segments. PMID- 22060719 TI - Small ruminant production systems and factors affecting lamb meat quality. AB - The influence of sheep production systems on the environment of the Mediterranean area and the different productive systems of lamb in Spain are described. Moreover the actual knowledge (90s decade) about factors influencing the quality of lamb meat is reviewed, highlighting the importance of productive and pre slaughter factors on carcass quality and post-slaughter factors on meat quality. Also the significance of culinary cultural back-ground on the acceptance of sheep meat is discussed. PMID- 22060720 TI - Robotic equipment in the meat industry. AB - Robotic technology is beginning to find uses in the meat processing industry. This paper attempts to describe the potential benefits and some of the problems in implementing robots for meat processing. An overview of some of the robotic equipment available and in development for beef, pork, lamb, poultry, fish and seafood processing is given. Standard industrial robots already perform meat industry tasks involving regular and uniform products and processes. Robotic automation is emerging for more skilled tasks but is not yet fully accepted or implemented in the meat industry. PMID- 22060721 TI - Environmental impact of pig meat production. AB - The aim of this paper is to examine the environmental effects of pig production and possibilities at farm level to limit these effects. According to the 'EC Nitrate Directive' the application of animal manure should not exceed 170 kg N/ha. Supply of animal manure in the 12 European member states exceeds 170 kg N per ha, approximately 13% of the number of holdings. The production of nitrogen from animal manure at member state level exceeds 170 kg N/ha in Belgium and The Netherlands. The performance and mineral excretion per sow and per fattening pig on Dutch farms in 1995 were estimated using data from 362 sow farms and 631 farms with growing-finishing pigs. Average annual P(2)O(5) excretion per sow and per fattening pig amounted to 14.0 and 5.0 kg year(-1), respectively. Average annual N-excretion per sow and per fattening pig amounted to 30.8 and 13.1 kg/ year respectively. Observed differences between farms in annual mineral excretion per animal are large. Farms with low annual mineral excretion have better productivity figures. The possibilities of reducing the mineral excretion are mainly dependent on the onset of the situation. In many cases lowering the mineral content in the feed alone will not be sufficient. There are possibilities for reducing the mineral excretion level but it takes time to implement the appropriate measures and they are not feasible for all farms. The emission of ammonia from animals which is produced in the barn can only be reduced by allowing new housing systems that meet specific environmental requirements. The emission of ammonia can be diminished by reducing the emitting surface, the slurry temperature, the air movement above the emission surface, the N contents and the pH of the slurry. Over the last few years, low emission housing systems for each pig category have been developed. PMID- 22060722 TI - Lipid stability in meat and meat products. AB - Lipid oxidation is one of the main factors limiting the quality and acceptability of meats and meat products. Oxidative damage to lipids occurs in the living animal because of an imbalance between the production of reactive oxygen species and the animal's defence mechanisms. This may be brought about by a high intake of oxidized lipids or poly-unsaturated fatty acids, or a low intake of nutrients involved in the antioxidant defence system. Damage to lipids may be accentuated in the immediate post-slaughter period and, in particular, during handling, processing, storage and cooking. In recent years, pressure to reduce artificial additive use in foods has led to attempts to increase meat stability by dietary strategies. These include supplementation of animal diets with vitamin E, ascorbic acid, or carotenoids, or withdrawal of trace mineral supplements. Dietary vitamin E supplementation reduces lipid and myoglobin oxidation, and, in certain situations, drip losses in meats. However, vitamin C supplementation appears to have little, if any, beneficial effects on meat stability. The effect of feeding higher levels of carotenoids on meat stability requires further study. Some studies have demonstrated that reducing the iron and copper content of feeds improves meat stability. Post-slaughter carnosine addition may be an effective means of improving lipid stability in processed meats, perhaps in combination with dietary vitamin E supplementation. PMID- 22060723 TI - Oxidation in traditional mediterranean meat products. AB - Lipid oxidation in dry-fermented sausages and dry-salted-hams, representative items of traditional Mediterranean pork products, is responsible for the production of compounds which can affect their organoleptic qualities and wholesomeness. Lipid-derived compounds make up an important share of the volatiles extracted from matured products, once the contribution of spices is removed, and contribute significantly to the flavour of old style products. The few reports available on oxysterols depict a total cholesterol oxidation rate of about 0.1%, a threshold level for toxic effects to occurin vitro but about 100 times lower of thein vivo toxicity dose. The value could perhaps be reduced with the use of antioxidants. Phospholipids are the main class of fats interested by lipolysis and unsaturated fatty acids are those most interested by oxidation. On that basis, the case of special feeding regimes, such as that of Iberian pigs, and the possible relevance of muscle fibre type on flavour development are discussed. PMID- 22060724 TI - Conference review panel. PMID- 22060725 TI - Infrared study of structural characteristics of Frankfurters formulated with olive oil-in-water emulsions stabilized with casein as pork backfat replacer. AB - This article reports an infrared spectroscopic (FT-IR) study on lipids and protein structural characteristics in frankfurters as affected by an emulsified olive oil stabilizing system used as a pork backfat replacer. The oil-in-water emulsions were stabilized with sodium caseinate, without (F/SC) and with microbial transglutaminase (F/SC+MTG). Proximate composition and textural characteristics were also evaluated. Frankfurters F/SC+MTG showed the highest (P < 0.05) hardness and lowest (P < 0.05) adhesiveness. These products also showed the lowest (P < 0.05) half-bandwidth of the 2922 cm(-1) band, which could be related to the fact that the lipid chain was more orderly than that in the frankfurters formulated with animal fat and F/SC. The spectral results revealed modifications in the amide I band profile when the olive oil-in-water emulsion replaced animal fat. This fact is indicative of a greater content of aggregated intermolecular beta-sheets. Structural characteristics in both proteins and lipids could be associated with the specific textural properties of frankfurters. PMID- 22060726 TI - Superexchange-like interaction of encaged molecular oxygen in nitrogen-doped water cages of clathrate hydrates. AB - Clathrate hydrates are a highly prospective material in energy and environmental fields, but the inherent nature of inclusion phenomena occurring in the stacked water cages has not been completely resolved yet. Investigating the magnetism of guest molecules is a new experimental approach in clathrate hydrate research to open the possibility of icy magnetic applications as a novel material as well as to understand the unrevealed host-guest interactions in icy inclusion compounds. In this study, we observed an indirect spin coupling between encaged dioxygen molecules via a nonmagnetic water framework through the measurement of guest magnetization. This spin coupling is reminiscent of superexchange coupling between magnetic ions through intervening oxygens in antiferromagnetic oxides, such as MnO and CoO. Theoretical calculations revealed that OH(-) incorporated in the framework induced the mixing of perpendicular pi* orbitals of two distant dioxygens and that ammonia doping into the hydrate cage leads to a longer lifetime of that orientation. PMID- 22060727 TI - Markedly reduced rate of diabetic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies. AB - OBJECTIVE: To determine whether screening for islet autoantibodies in children prevents ketoacidosis and other metabolic complications at diabetes onset and improves the clinical course after diagnosis. SUBJECTS AND METHODS: The German BABYDIAB and the Munich Family Study follow children with a first-degree family history of type 1 diabetes for the development of islet autoantibodies and type 1 diabetes. The Diabetes Prospective Documentation (DPV) Initiative registers and collects information on pediatric patients with type 1 diabetes throughout Germany. Here, clinical characteristics at diabetes onset [ketoacidosis, mean hemoglobin A1c (HbA1c), and length of hospitalization] and the 5-yr clinical course (HbA1c and insulin dose) of screened and followed islet autoantibody positive children (n = 101) and 49 883 non-screened children within the DPV registry were compared. RESULTS: At diabetes onset, children who were followed after screening and were positive for islet autoantibodies had lower HbA1c (8.6 vs. 11%, p < 0.001) and a lower prevalence of diabetic ketoacidosis (3.3 vs. 29.1%, p < 0.001). Screened children also had a shorter hospitalization period at onset (11.4 vs. 14.9 d, p = 0.005). Similar results were observed when the analysis was restricted to 759 non-screened DPV children with a first-degree family history of type 1 diabetes. No differences between screened and non screened children were observed with respect to HbA1c and insulin dose during the first 5 yr after diagnosis. CONCLUSIONS: Screening for islet autoantibodies in children likely leads to earlier diabetes diagnosis resulting in less complications at diagnosis. However, no substantial benefit in the clinical outcome during the first 5 yr after diagnosis was observed. PMID- 22060728 TI - Abstinence orientation and treatment practice: an analysis of German settings providing opioid maintenance therapy. AB - We examined whether differences in abstinence orientation are related to differences in treatment patterns by analyzing assessment data from a total of 161 German treatment settings offering opioid maintenance therapy. According to an index value, settings were divided into low (LAOs), medium (MAOs), and high abstinence-oriented settings (HAOs). Logistic, multinomial logistic, and linear regression analyses were carried out. HAOs prescribed lower maximum dosages of methadone and enforced rules for handling of concomitant drug use more rigidly than MAOs and LAOs. Patients in HAOs were more likely to undergo psychotherapeutic and psychiatric treatment than in MAOs and LAOs. Limitations, conclusions, and future research are suggested. PMID- 22060729 TI - Comparisons between Q(ST) and F(ST) --how wrong have we been? AB - The comparison between quantitative genetic divergence (Q(ST) ) and neutral genetic divergence (F(ST) ) among populations has become the standard test for historical signatures of selection on quantitative traits. However, when the mutation rate of neutral markers is relatively high in comparison with gene flow, estimates of F(ST) will decrease, resulting in upwardly biased comparisons of Q(ST) vs. F(ST) . Reviewing empirical studies, the difference between Q(ST) and F(ST) is positively related to marker heterozygosity. After refuting alternative explanations for this pattern, we conclude that marker mutation rate indeed has had a biasing effect on published Q(ST) -F(ST) comparisons. Hence, it is no longer clear that populations have commonly diverged in response to divergent selection. We present and discuss potential solutions to this bias. Comparing Q(ST) with recent indices of neutral divergence that statistically correct for marker heterozygosity (Hedrick's G'st and Jost's D) is not advised, because these indices are not theoretically equivalent to Q(ST) . One valid solution is to estimate F(ST) from neutral markers with mutation rates comparable to those of the loci underlying quantitative traits (e.g. SNPs). Q(ST) can also be compared to Phi(ST) (Phi(ST) ) of amova, as long as the genetic distance among allelic variants used to estimate Phi(ST) reflects evolutionary history: in that case, neutral divergence is independent of mutation rate. In contrast to their common usage in comparisons of Q(ST) and F(ST) , microsatellites typically have high mutation rates and do not evolve according to a simple evolutionary model, so are best avoided in Q(ST) -F(ST) comparisons. PMID- 22060730 TI - Intermolecular vibrations and diffusive orientational dynamics of Cs condensed ring aromatic molecular liquids. AB - The ultrafast dynamics, including the intermolecular vibrations and the diffusive orientational dynamics, of the neat C(s) symmetry condensed ring aromatic molecular liquids benzofuran, 1-fluoronaphtalene, and quinoline were investigated for the first time by means of femtosecond Raman-induced Kerr effect spectroscopy. To understand the features of these C(s) condensed ring aromatic molecular liquids, reference singular aromatic molecular liquids, furan, fluorobenzene, pyridine, and benzene, were also studied. High quality low frequency Kerr spectra of the aromatic molecular liquids were obtained by Fourier transform deconvolution analysis of the measured Kerr transients. The Kerr spectra of the C(s) condensed ring aromatic molecular liquids are bimodal, as are those of the reference singular aromatic molecular liquids. The first moment of the intermolecular vibrational spectrum and the peak frequencies of the high- and low-frequency components in the broad spectrum band were compared with their molecular properties such as the rotational constants, molecular weight, and intermolecular (bimolecular) force. The comparisons show that the molecular volume (related to molecular weight and rotational constants) is a dominant property for the characteristic frequency of the entire intermolecular vibrational spectrum. The observed intramolecular vibrational modes in the Kerr spectra of the aromatic molecular liquids were also assigned on the basis of the ab initio quantum chemical calculation results. In their picosecond diffusive orientational dynamics, the slowest relaxation time constant for both the condensed ring and singular aromatic molecular liquids can be accounted for by the simple Stokes-Einstein-Debye hydrodynamic model. PMID- 22060731 TI - Early immune outcome of retroperitoneal laparoscopic radical nephrectomy for localized renal cell carcinoma: a prospective, randomized study. AB - OBJECTIVES: We evaluated differences in cytokine responses and T-lymphocyte subsets following retroperitoneal laparoscopic and conventional open radical nephrectomies for localized renal cell carcinoma (RCC). METHODS: A total of 62 patients with T(1)N(0)M(0) staged RCC were randomized to either retro laparoscopic (n = 31) or open (n = 31) radical nephrectomy. Plasma levels of interleukin-1beta (IL-1beta), IL-6, and tumour necrosis factor-alpha (TNF-alpha) were measured separately by enzyme linked immunosorbent assay (ELISA) preoperatively and on postoperative days 1 and 5. Levels of CD3(+), CD4(+) and CD8(+) as well as the CD4(+):CD8(+) ratio were acquired by flow cytometry at the same time points. RESULTS: Levels of IL-1beta, IL-6 and TNF-alpha increased significantly compared to preoperative values in both groups (p < 0.05) on postoperative day 1, and all the parameters in the open group were significantly higher than those in the retro-laparoscopy group (p < 0.05). On postoperative day 1, the levels of CD3(+) and CD4(+) and the CD4(+):CD8(+) ratio decreased markedly compared to preoperative values for both groups (p < 0.05). Elevations of the CD4(+):CD8(+) ratio in the retro-laparoscopy group (p < 0.05) and the CD8(+) level in the open group (p < 0.05) were observed when compared with the other group. On postoperative day 5, the levels of CD3(+) and CD4(+) and the CD4(+):CD8(+) ratio in the retro-laparoscopy group, as well as the level of CD8(+) in the open group, returned to about preoperative levels (p < 0.05). Follow-up ranged from 4 to 14 months postoperatively in all 62 patients with a 100% cancer-specific survival rate in both groups. CONCLUSIONS: Retroperitoneal laparoscopic radical nephrectomy is associated with the milder cytokine responses caused by trauma and inflammation and the better preserved distribution of T lymphocytes. PMID- 22060732 TI - Prostate cancer survival in Trinidad: Is PSA a prognostic factor? AB - BACKGROUND: Prostate cancer is the most common malignancy among men in the western hemisphere, including Trinidad and Tobago. The aim of this study is to describe the epidemiological features of prostate cancer among patients admitted to a tertiary level teaching hospital during 2002 to 2005. We assessed the long term survival of patients with prostate cancer and the epidemiology of the disease. METHODS: We reviewed the admissions data for the period 2002-2005. Demographic, clinical and outcomes (survival or death) data were collected and analysed, using SPSS version 16. Statistical analysis included Kaplan-Mier survival analysis, Cox regression models and the log-rank test. A p value of <0.05 was considered statistically significant. RESULTS: Of the 1250 cases reviewed, 242 participants were selected. Patients of African ancestry, older than 60 years and a Gleason score greater than 7 had an increased risk of mortality. Patients with prostate-specific antigen (PSA) >=100 ng/L had a 3-fold increased risk of mortality. Survival rates declined between 2002 and 2005. CONCLUSION: This is the first study of its kind to demonstrate survival rates among patients with prostate cancer in Trinidad. The following epidemiological features were identified: average age of occurrence of 71 years, ethnic disparity with higher occurrence in African men than all other ethnic groups and a PSA of >100 ng/dL. These features were associated with a 3-fold higher risk of death. A Gleason score of 8 to 10 was also associated with lower survival rates. PMID- 22060736 TI - Attachment of bacteria to meat surfaces: A review. AB - The mechanism of attachment of bacteria to meat surfaces involves two consecutive stages: reversible and irreversible attachment. The dependence of attachment on various factors is discussed: hydrophobicity and cell surface charge, bacterial structures, type of meat surface, pH, temperature, presence of chemical substances, etc. The consequences of these findings for slaughter hygiene, kitchen hygiene, etc., are clear; avoid bacterial contamination. PMID- 22060737 TI - A practical method to prevent dark-cutting (DFD) in beef. AB - A method for the prevention of dark-cutting in beef, based on recognition of social relationships within groups of bulls, was tested on 2234 bulls slaughtered under commercial conditions. When the influence of time between loading the animals and slaughter was eliminated statistically, the bulls of the socially stablized group showed the lowest pH(24) values, whereas those of the socially unstable group showed the highest ones. When the type of social group was eliminated statistically, the earlier slaughtered animals had lower pH(24) values than those slaughtered later. When the two major factors were integrated, there was no statistically significant difference in the pH(24) values in bulls of the socially stabilized group whether they were slaughtered immediately after transport or during the following day. In contrast, in bulls from the socially unstable group, the pH(24) values increased substantially after overnight lairage at the abattoir. In conclusion, for longer transportion, bulls from loose housing with stable social relationships should be used. It is necessary to keep the same social groups from loading to slaughter, strictly avoiding any mixing of strange bulls. Bulls from tethered stalls should be transported and slaughtered within as short a time after regrouping as possible. PMID- 22060738 TI - The effectiveness of examining early post-mortem musculature to predict ultimate pork quality. AB - Variations in pork quality reflect value differentials. However, only when they can be easily, accurately, rapidly and cost-effectively detected, can swine producers expect to eliminate poor quality from their herds through genetic selection, and can the industry be expected to take the necessary environmental precautions to prevent poor quality. This study was designed to assess the effectiveness of various techniques thought to predict ultimate pork quality through the examination of the physical and chemical properties of early post mortem (PM) musculature. Based on stiffness and pH 30, 285 carcasses were selected. This selection procedure ensured a wide variation in ultimate quality. Using 12 instruments simultaneously, temperature, stiffness, electrical properties, lightness properties, and pH 45 of the early PM longissimus thoracis et lumborum were recorded to predict ultimate quality. Based on post-rigor light reflection and water-holding capacity (WHC), quality was assigned to one of five arbitrary groups. Of all techniques tested, the only one with any potential for adequate prediction of quality categories was pH 45. Combination of different techniques did not significantly increase predictive values. For predicting quality of single carcasses, pH 45 should not be considered satisfactory. However, based on our success in selecting carcasses representing quality variation for this study and the results obtained from the study, using pH 45 and muscle stiffness to select groups of carcasses is feasible. We conclude that the techniques used early post mortem are not appropriate for predicting ultimate pork quality for single carcasses. At present we recommend that only post-rigor muscle be considered, and that ultimate pH, light reflection and a measure of WHC should be used. PMID- 22060739 TI - Influence of cooking on benzo(a)pyrene content in smoked sausages. AB - The changes in benzo(a)pyrene (BaP) content of smoked sausages were monitored during 1 h cooking. During this time, the BaP content decreased from 4.80 to 1.87 MUg/kg. The maximum drop in BaP content was reached in the first 20 min of cooking. Two factors affected the course of BaP changes, viz. water-holding capacity and the fat content. After excluding these factors, there was a high correlation coefficient of 0.996 between time of cooking and BaP content, which confirmed an inverse relationship between the decrease in BaP content and time of cooking. The BaP decrease was directly proportional to the decrease of fat content during cooking, when the relatively high BaP content of 7.71 MUg/kg was found in the cooked-out fat. PMID- 22060740 TI - Spray chilling of lamb carcasses. AB - Two spray-chilling treatments were developed to improve appearance and reduce weight loss during lamb chilling. Rates of cooling and weight loss and meat quality were compared to conventionally chilled carcasses. The first treatment was an intermittent spray during the first 3 h of chilling. The second consisted of only two sprays at 2 h and 10 h post mortem. The conventional control was a two-stage process, with air at 10 degrees C and 1 m/s up to 10 h post mortem, followed by air at 0 degrees C and 1 m/s for a further 14 h. Both treatments significantly reduced weight loss at 24 h post mortem compared to conventional, from 2.20% to 0.86% and 1.20%, respectively. During a further 4 days storage, the savings were maintained, with weight losses being 3.97%, 2.97% and 3.19%, respectively. There were small (<1 h) but significantly reductions in the cooling times of spray-chilled loins and legs, attributed to sustained evaporative cooling of the continually wetted surfaces. No effects on texture or drip loss and only slight effects on surface lean and fat colour were found. Variation in texture between animals within treatments was far greater than between treatments and could not be accounted for by variations in cooling rates. PMID- 22060741 TI - Growth and carcass characteristics of Angus and American Wagyu steers. AB - Ten purebred Angus and ten crossbred (3/4-7/8) American Wagyu steers were fed a corn and barley-based diet for 552 days and slaughtered. All USDA and Japanese yield and quality grade factors were evaluated and the amount of extractable lipid and moisture in totally trimmed muscle was determined. Angus steers gained 0.9 kg/head/day and American Wagyus gained 0.7 kg/head/day. This difference in growth rate resulted in Angus steers having a heavier final weight (P < 0.05). Angus steers required less feed per unit of gain than did American Wagyu steers. Adjusted fat thickness over M. longissimus dorsi opposite the 12th rib was approximately 3.5 cm and was not statistically different between the two breeds (P > 0.05). Average ribeye area and kidney, pelvic and heart fat were similar for the two breeds. The calculated USDA yield grade for both breeds exceeded 6. Average USDA marbling score was nearly a degree of marbling higher for American Wagyu than for Angus, but variation within breed groups was high. Average USDA quality grade was well into USDA Prime for all carcasses and did not differ by breed (P > 0.05). Japanese yield grade factors were similar for both breeds except for cold left side weight and the yield estimation which includes an adjustment factor that favors American Wagyu. American Wagyu steers merited a higher Japanese marbling score than did Angus (P < 0.05). Beef color score, firmness, texture and firmness and texture grade were also different between the breeds (P < 0.05). Fat colour, luster and quality were not different (P > 0.05). These data clearly show that some American Wagyu steers have the genetic ability to deposit as much marbling as Japanese Black cattle raised in Japan. PMID- 22060742 TI - Changes in pH and water holding properties of Longissimus dorsi muscle during beef ageing. AB - The effects of vacuum packaging, chilling rate (slow or fast), and fat cover thickness (<= 4 mm or 7-8 mm) on pH and water-holding properties of longissimus dorsi muscle were assessed during beef ageing. The longissimus dorsi muscles were aged on the carcass or in vacuum packaging. Muscle samples were taken on days 0 (24 h post-mortem), 2, 4, 8, 12 and 16 to measure these properties. Ageing time significantly influenced muscle pH and cooking loss; however, interaction fat * chill * time affected press juice. The pH was also influenced by vacuum-packaged ageing. Press juice positively correlated with cooking loss and pH. PMID- 22060743 TI - The effects of spray and blast-chilling on carcass shrinkage and pork muscle quality. AB - Combinations of blast- and spray-chilling of pork carcasses were compared to spray-chilling at conventional chilling temperatures with regard to carcass shrinkage during chilling and pork muscle quality. In experiment 1, pork sides were spray-chilled at 1 degrees C for the first 10 h (40 spray cycles of 60-s duration every 15 min) of cooling or blast-chilled at -20 degrees C for 1, 2 or 3 h followed by spray-chilling for 9, 8 or 7 h duration, respectively. All pork sides were then chilled to 24 h post mortem at 1 degrees C. Experiment 2 followed the same procedures as experiment 1, except that -40 degrees C was used as the blast-chill temperature. Carcass shrinkage was similar for all treatments in experiment 1 at 24 h ranging from 0.5-0.7 g 100 g(-1). Blast/spray-chilling increased the rate of chilling and reduced the rate of post-mortem pH decline in two muscles (longissimus thoracis, LT and semimembranosus, SM) compared to the combined conventional/spray-chill treatment. Carcasses that were blast-chilled for 3 h had LT muscles that were darker with a higher protein solubility, less drip loss, shorter lengths and higher shear values compared to those from carcasses in the conventional/spray-chill treatment. In experiment 2, carcasses blast-chilled for 3 h at -40 degrees C recorded a weight gain at 24 h of 0.4 g 100 g(-1), compared to a weight loss in all other treatments (0.2-0.4 g 100 g( 1)). Muscle colour was darker in both the LT and SM of carcasses blast-chilled for 3 h at -40 degrees C compared to carcasses from the conventional/spray-chill treatment, but most other measurements of muscle quality showed an inconsistent response to chilling treatment. PMID- 22060744 TI - Flavour- and tenderness-related quality characteristics of goat and sheep meat. AB - The quality characteristics of 27 Angora goats, Boer goats and sheep carcases were compared. Significant differences exist between the quality characteristics of sheep meat and Angora or Boer goat meat. Sheep meat has a more intense aroma, it is more tender, contains less fibrous tissue residue and the species flavour is more pronounced (typical) than that of Angora and Boer goat meat. In general, goat meat was found to be significantly different to sheep meat, the Angora to a lesser extent, however, than the Boer goat. This study confirms the fact that the meat of younger animals is more tender, contains less fibrous tissue residue and the species flavour is less typical than that of older animals. This was irrespective of whether it was obtained from sheep, Angora or Boer goat. With increasing fatness of carcases, the tenderness and species flavour of the cooked cuts increased significantly. PMID- 22060745 TI - Cooking- and juiciness-related quality characteristics of goat and sheep meat. AB - Significant differences exist between the quality characteristics of meat obtained from 27 sheep, Angora and Boer goat carcases, when compared. Sheep meat showed greater drip loss than goat meat and was more juicy than that of Angora and Boer goat meat. In general, Angora goat meat was found to be more juicy than Boer goat meat. Drip loss increased significantly with increased animal age. Meat of younger animals (no permanent incisors) was more juicy (initial and sustained) than that of older animals (7-8 permanent incisors). This was irrespective of whether it was obtained from sheep, Angora or Boer goats and was confirmed by the expressible moisture measurements. Higher drip, evaporation and total cooking loss were reported when carcases had increased fat content. With increasing fatness of carcases, the juiciness of the cooked cuts decreased and the expressible moisture content of the meat increased. PMID- 22060746 TI - The effect of scalding on subcutaneous and ham temperatures and ultimate pork quality. AB - Scalding of pig carcasses (n = 34) at 60 degrees C for a period of at least 5.5 to 7.5 min gave satisfactory dehairing results, with the exception of autumn hair for which a longer period (9 mins) was required. Temperature curves were recorded for a subcutaneous position in the ham (n = 26) between the rind and the underlying fat layer. These showed a curve starting at about 30.8 degrees C and increasing to an asymptotic value of 53 degrees C during scalding. Results of calculations with a finite element model of a flat layer of muscle covered with a layer of 1.0 cm fat broadly showed the same temperature increase at about 0.5 cm below the surface as the actual values measured. Immediately after dehairing, about 1.5 mins after finishing scalding, the subcutaneous temperature had already dropped to 46.1 +/- 3.0 degrees C, which was considerably higher than the muscle temperature at the same position at a depth of 5 cm under the skin (40.6 degrees C). The heat removal and temperatures during the cooling period after scalding were also calculated. It can be concluded that the increase in temperature due to scalding has only a minor influence on muscle temperature and that meat quality (pH, FOP) is not affected. PMID- 22060747 TI - Soluble CD163. AB - CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163) at 0.7-3.9 mg/l in healthy individuals. The function of sCD163 is unknown, but during inflammation and macrophage activation, sCD163 levels increase acutely due to metalloproteinase-mediated cleavage near the cell membrane. It is now evident that sCD163 is very useful as a biomarker of macrophage activation in various inflammatory diseases, such as macrophage activation syndrome, sepsis, and liver disease. Moreover, sCD163 is a general risk marker of comorbidity and mortality in several chronic inflammatory disease states. Recently, sCD163 has been shown to be strongly associated with later development of type 2 diabetes in both lean and obese subjects, likely due to macrophage infiltration of adipose tissue and the liver. This review summarizes the current knowledge on the regulation of sCD163 in normal and pathological states and also deals with analytical aspects of sCD163 measurements in biological samples. PMID- 22060748 TI - The NET effect of clot formation. PMID- 22060749 TI - Prediction of post-treatment hypothyroidism using changes in thyroid volume after radioactive iodine therapy in adolescent patients with Graves' disease. AB - BACKGROUND: The goal of iodine-131 therapy for pediatric Graves' disease is to induce hypothyroidism. However, changes in post-treatment thyroid volume have not been investigated in pediatric and/or adolescent patients. OBJECTIVE: The aim of this retrospective study was to examine whether changes in thyroid volume predict post-treatment hypothyroidism in adolescent Graves' disease patients. PATIENTS AND METHODS: We used ultrasonography to examine changes in thyroid volume, and also assessed thyroid functions, at 0, 1, 3, 5, 8 and 12 months after iodine-131 treatment in 49 adolescents ranging in age from 12 to 19 years retrospectively. Based on thyroid function outcome at 12 months, patients were divided into two groups: 29 patients with overt hypothyroidism requiring levothyroxine replacement and 20 without overt hypothyroidism. We compared changes in post-radioiodine thyroid volume between the two groups. RESULTS: About 90% of patients whose thyroid volume at 3 months after iodine-131 administration was less than 50% of the original volume were hypothyroid by one year after treatment (positive predictive value 88%, sensitivity 75.9%, specificity 85.0%). CONCLUSIONS: We believe ultrasonographic measurement of thyroid volume at 3 months after iodine 131 to be clinically useful for predicting post-treatment hypothyroidism in adolescent Graves' disease patients. PMID- 22060750 TI - Chopping temperature effects on the characteristics and chilled storage of low- and high-fat pork Bologna sausages. AB - The object of this study was to investigate the influence of chilled storage (2 degrees C) and final chopping temperatures (8, 15 and 22 degrees C) on the characteristics and stability of Bologna sausage containing two levels of fat (8.5 and 23%). When the fat level was reduced there was a significant decrease in penetration force and an increase in both cooking and purge loss. A lower chopping temperature reduced purge loss during chilled storage. In general, an inverse relationship was found between chopping temperature and penetration force. Chopping temperature did not influence total aerobic count, but during chilled storage counts were significantly higher in the low fat sausages. PMID- 22060751 TI - Effect of post-slaughter processing and freezing on the functionality of hot boned meat from young bull. AB - The effects of variation in the times of mincing post mortem (2, 4, or 6 h), pre rigor salting (1.5% wt wt ) and freezing rate [fast (10 min, liquid nitrogen); medium (4-6 h at -40 degrees C and 0.8 m s(-1) air velocity); or slow (36-38 h at -10 degrees C and 0.1 m s(-1) air velocity followed by 12 h at -20 degrees C and 0.1 m s(-1) air velocity)] on the functionality of young bull meat were examined using hot-boned forequarters. At 52 h post packaging, the meat was thawed (72 h at 4 degrees C), its pH measured, and it was used to make finely comminuted batters. Cook yield and stress and strain of the cooked batters were measured. Time of mincing had no effect on meat pH, cook yield or stress and strain. There was a significant interaction (P < 0.05) between pre-rigor salting and freezing rate for pH. Freezing rate did not affect the pH of pre-rigor salted meat whereas the pH of unsalted pre-rigor meat was highest at the fastest freezing rate. Meat salted pre-rigor had a significantly (P < 0.05) higher pH than the post-rigor chilled control. Pre-rigor salting decreased the stress values of cooked batter whereas the slowest freezing rate increased stress. Stress and strain values for cooked batters from thawed meat were not significantly different from the values for batters made from the unfrozen control. Cook yields of batters made from pre-rigor frozen meat were higher than that of the postrigor control but not significantly so. The results indicate that suppliers can use pre-rigor salted and frozen meat when manufacturing comminuted products without major detrimental effects on the cook yield and texture of the finished product. PMID- 22060752 TI - Release of free amino-acids during ageing in bovine meat. AB - The amounts of free amino-acids in Longissimus dorsi (LD), Triceps brachii (TB) and Rectus femoris (RF) from 8 Friesian 20-month old bulls were determinated using gas chromatography. The amounts of free amino-acids released during storage from 3 to 14 days post mortem at 4 degrees C depended on the muscle. Total free hydroxyproline in LD increased from 3% at 3 days to 11% at 14 days post mortem. Free amino-acids seemed to increase more after 10 days than between 3 and 10 days post mortem. The myofibrillar fragmentation index was highly correlated with leucine, isoleucine, threonine and methionine contents in TB and RF. MFI was correlated with hydroxyproline, leucine and isoleucine in LD. PMID- 22060753 TI - Enzymological investigations on the causes for the PSE-syndrome, I. Comparative studies on pyruvate kinase from PSE- and normal pig muscles. AB - A fast breakdown of glycogen is observed in muscles of stress-susceptible pigs leading to pale, soft and exudative (PSE) meat. We report a comparative study of pyruvate kinase from muscles of normal and PSE-prone pigs. Compared with enzyme from normal muscle, pyruvate kinase isolated from PSE-muscle shows a five times lower K(m) for phosphoenol pyruvate and a more than ten times higher k (cat)K (m) value. The pH-dependency of the enzymatic activity is shifted to more acidic values for pyruvate kinase from PSE muscles. According to isoelectric focusing, pyruvate kinase from PSE muscle consists of three isoforms, while only two isoforms are detectable in pyruvate kinase preparations from normal pigs. The various isoforms were isolated by preparative isoelectric focusing and their steady-state properties were compared. Isoform 3, which is found only in PSE muscle, shows a 10-fold higher specific activity, a 30-fold lower K(m) value and a 100-fold increased k (cat)K (m) value for phosphoenol pyruvate compared to isoform 1. The presence of isoform 3 in PSE-muscle appears to be responsible for the high activity of this enzyme under the more acidic conditions prevailing in PSE-muscle. In vitro phosphorylation and dephosphorylation experiments using total enzyme and purified isoenzyme 1 suggest that isoforms 2 and 3 arise from isoform 1 by phosphorylation. Thus protein phosphorylation seems to be responsible for the shift in activity of pyruvate kinase, a key enzyme of glycolysis, under the acidic conditions of PSE-muscles. PMID- 22060754 TI - Enzymological investigations on the causes for the PSE-syndrome, II. Comparative studies on glycogen phosphorylase from pig muscles. AB - In order to investigate the cell biological causes for the fast breakdown of glycogen which is observed during the development of the PSE (pale, soft, exudative) syndrome in muscles of stress-susceptible pigs, muscle glycogen phosphorylase (GP) as a key enzyme in two isoforms, a and b, of the energy turnover was isolated from M. longissimus dorsi of normal and PSE-prone pigs of the German Landrace. GP b as well as GP a from normal and PSE-muscles exist in a dimeric form with a molecular weight of 97 000 D per subunit. The tendency for tetramerization of GP b increases in the presence of ATP, whereas the enzyme activity is simultaneously inhibited. The catalytic activities of GP a and GP b from both groups of animals show an optimum at pH 7.0. GP b can be activated to GP a by phosphorylation with the result of a 25% higher optimum specific activity in the case of normal and PSE-muscles. In interaction with glycogen and glucose-1 phosphate GP b follows the characteristics of a Michaelis-Menten kinetic, whereas the binding of AMP and phosphate proves to be allosteric. In comparison of the structural and kinetic characteristics of GP from normal as well as PSE-muscles no significant differences could be determined, indicating that GP does not belong to those factors which are triggering an accelerated energy turnover of ATP in muscles of stress-susceptible pigs. PMID- 22060755 TI - Omega-3 fatty acids in pig nutrition: Implications for the intrinsic and sensory quality of the meat. AB - Seventy-eight hybrid pigs (Pietrain * Seghers hybrid cross, 38 barrows and 40 gilts) were fed ad libitum diets, containing either 0.4%, 0.7% or 1.0% alpha linolenic acid (C18:3n-3), originating from linseed. The variation in polyunsaturated fatty acid content in the feed (1.19%, 1.52% and 1.88%, respectively) was mainly attributed to variations in alpha-linolenic acid content. Meat quality evaluated by physical measurements (pH, light scattering, conductivity, colour, light reflection, tenderness, water holding capacity) was not influenced, to any significant extent, by the fatty acid composition of the feed. A subjective judgement of cohesiveness revealed no abnormalities. Dietary fat source, sex and intramuscular fat (IMF) level affected the fatty acid pattern of the IMF. The alpha-linolenic content in the IMF increased from 1.2% to 2.3% for the barrows and from 1.4% to 2.9% for the gilts with increasing alphalinolenic acid content in the feed. A multiple paired comparison test for taste, tenderness and juiciness on 45 meat samples (M. longissimus thoracis) revealed no significant differences among the feed groups. PMID- 22060756 TI - Monitoring nitrite and nitrate residues in frankfurters during processing and storage. AB - Frankfurter-type sausages were prepared in a pilot plant with different concentrations of NaNO(2) (75, 125 or 250 ppm) combined or not with 200 ppm KNO(3). A meat system, free of curing agents, was also used as control. Nitrite and nitrate levels were tested in various processing steps and over 120 days storage at 3 degrees C of the vacuum-packaged frankfurters. Little influence of the originally added nitrite level on the amount of nitrate formed was observed. Important losses of nitrite and nitrate were due to cooking. Thereafter about 50% of the nitrite added initially remained in this form in all samples (39, 59 and 146 ppm, respectively) and between 10 and 15% as nitrate. When only nitrate was initially added, formation of nitrite after cooking was observed (maximum level 43 ppm NaNO(2)). Formulations prepared with both nitrate and nitrite showed no significant differences (p < 0.01) respect to their nitrite or nitrate counterparts. A good correlation among nitrite and nitrate levels and storage time was showed by multiple linear regression analysis. It is concluded that the use of nitrate in combination with nitrite in cooked meat products seems to have little technological significance and adds to the total body burden of nitrite. PMID- 22060757 TI - Prediction of carcass composition in the rabbit. AB - Carcass composition of two synthetic rabbit breeds was predicted from retail cuts and external measurements by using regression equations. Breed R has a higher adult weight and reaches slaughter weight 1 week before breed V. Sixty rabbits of each breed were slaughtered when they (approximately) reached the Spanish commercial liveweight of 2kg. The carcasses were measured and retailed according to the norms of the World Rabbit Scientific Association. Rabbit carcass composition is well defined by meat percentage of the commercial carcass and ratio meat bone . External measurements on the carcass, retail cuts and meat of retail cuts or muscular masses are all bad predictors of carcass meat percentage or ratio meat bone (R(2) < 0.53). The ratio meat bone of the hind leg can give reasonable predictions for carcass meat percentage and meat bone ratio (R(2) = 0.60 and 0.69). Dissectible carcass fat weight and dissectible carcass fat percentage can be predicted by the perirenal fat weight (R(2) = 0.77 and 0.69). Fat depots had a low predictive power for fat percentage of the dissected meat in the half carcass. PMID- 22060758 TI - Carcass composition and meat characteristics of two rabbit breeds of different degrees of maturity. AB - Carcass and meat characteristics of rabbits from two synthetic breeds of different size were compared. Breed R had a higher adult weight and reached slaughter weight 1 week before breed V. Sixty rabbits of each breed were slaughtered when they (approximately) reached the Spanish commercial liveweight of 2 kg in order to compare their carcasses and meat quality. The carcasses were measured and retailed according to the norms of the World Rabbit Scientific Association. Breed R had a considerably more developed liver, a less developed hind part, and a more developed thoracic cage. Dissectible fat content was 3.1% and 2.5% of the carcass weight for the breeds V and R, respectively. Meat content was higher in the V breed than in the R breed (53 and 51% with respect to the chilled carcases). The ratio meat bone was better for breed V (2.18 and 2.05, respectively). Muscular fat content, estimated in the meat of one side of the carcass, was higher for breed V. All these differences are related to the lower degree of maturity of breed R at equal weights. Muscular pH, measured on the B. femoris and on the M. Longissimus lumborum at the level of the 5th lumbar vertebra, was the same for both breeds. Colour was measured on the carcass surface and in cuts of the M. Longissimus lumborum. Some colour differences were found for the carcass surface, but not for the meat. PMID- 22060759 TI - Prediction of composition traits of young Charolais bull carcasses using a morphometric method. AB - The relationships among morphological traits and bovine carcass composition traits were analysed in order to select carcass measurements to derive equations for predicting muscle weight, percentage of muscle and muscle to bone ratio. The sample, constituted by 35 young Charolais bulls slaughtered at 18 months old, was homogeneous, e.g. half carcass weight = 225 +/- 13.2 kg (standard deviation), carcass fat% = 6.4 +/- 1.0, carcass muscle% = 74.58 +/- 1.47, carcass bone% = 16.87 +/- 0.83. Carcasses were weighed and a sub-group of carcass measurements was selected from the results of a principal component analysis, performed on 76 measurements taken from carcass photographs. The computation of the best combination of variables for prediction was based on the Mallows' Cp statistic and linear regression. The percentage of muscle was best predicted by only three carcass measurements with a relatively low value of fit (R(2) = 0.70). When carcass weight was added to the same measurements to obtain the best prediction for muscle weight, the fit was high (R(2) = 0.98). The prediction of muscle to bone ratio required nine variables and again the fit was high (R(2) = 0.90). PMID- 22060760 TI - Effects of breed, feed level and conditioning time on the tenderness of pork. AB - This study of 80 pigs compared the effects of breed (Duroc vs Large White), feed level (High vs 0.8 High, termed Low) and conditioning time (1 vs 10 days at 1 degrees C) on the tenderness and other aspects of the eating quality of pork. Conditioning time had the biggest effect (increase of 1.0 units on 1-8 taste panel scale between 1 and 10 days) and this was associated with an increase in the myofibrillar fragmentation index (MFI) from 19 to 24 units. Tenderness was not different between the two breeds although pork flavour intensity and overall liking scores were higher in Durocs. Durocs had higher concentrations of total lipid (marbling fat) in muscle (13.7 and 5.4 mg/g) and most polyunsaturated fatty acids except alpha-linolenic (C18:3 n-3) were at lower concentrations in Durocs, reflecting dilution of phospholipid fatty acids within a larger total lipid pool. Pigs fed at the high level were fatter than those fed restrictedly in terms both of P2 fat thickness and marbling fat. There was also a tendency, although not significant, for the meat to be more tender. When the data from all pigs were pooled, MFI was shown to correlate well with tenderness (r = 0.45) and marbling fat with juiciness (r = 0.36). PMID- 22060761 TI - Veal colour assessment with three wavelengths. AB - A method to derive reflectance spectra and colour coordinates of meat by measurement of reflectance at only three wavelengths, 480, 570 and 620 nm has been developed, by treating the spectra of a meat sample as a linear combination of the spectra of the three major myoglobin derivatives (reduced myoglobin, oxymyoglobin and metmyoglobin). Applied to 300 samples of Semitendinosus and Longissimus dorsi veal muscles at different times post mortem (24 h to 9 d), colour differences DeltaE (*) between the derived spectra and the real ones were about 1.5 units. The total pigment content, with high correlation with the extraction method (P < 0.02), and the relative proportions of the derivatives can also be estimated. PMID- 22060762 TI - Incorporation of dietary polyunsaturated fatty acids in pork tissues and its implications for the quality of the end products. AB - One hundred and ten fattening pigs of a Pietrain * Hybrid cross-barrows and gilts in equal numbers-were distributed over five feeding formulas, containing increasing amounts of polyunsaturated fatty acids (PUFA), in the form of rapeseed. The aim of the study was to evaluate the maximum admissible amount of PUFA in the pig diet before problems-in terms of backfat consistency and storage stability-occur and to investigate the incorporation of dietary PUFA in intramuscular fat as well. A tendency towards reduced feed (energy) intake was obvious from the 7% rapeseed inclusion level, apparently resulting in a somewhat thinner backfat layer. None of the backfat samples showed a visible yellow discolouration instead thin backfat layers appeared as pink. Backfat consistency was lower for gilts and decreased with increasing dietary PUFA levels. PUFAs in the feed and in backfat were very well correlated (0.8-0.9) as expected; correction for de novo fat synthesis (by means of backfat thickness) did not alter the correlations within one sex group. Thresholds for PUFA in feed-15 g PUFA/kg feed-and for PUFA in back-fat-iodine value of 70 or 15% PUFA-were all surpassed in this experiment: 18 g PUFA/ kg feed resulted in maximally 22% PUFA in the outer backfat layer. The backfat PUFA limit was reached at relatively low feed PUFA levels. This might be explained by thin and hence more unsaturated backfat layers in lean or underweight pigs. Oxidative stability of the backfat after storage for 1 year in the freezer was satisfactory. The total intramuscular fat (IMF) content showed no obvious relationship with diet, in contrast with sex: barrows had more IMF than gilts. IMF consisted in 80% apolar phase and 20% polar fraction. The apolar fraction showed similar feed and sex tendencies as backfat, although correlations between feed and apolar fraction PUFAs were higher for gilts than for barrows. The amount of phospholipid was invariable throughout all treatments. Only linoleic acid-the major fatty acid-showed some feed and sex influence. In view ofthf results obtained the threshold for feed and backfat PUFA can be as high as, respectively, 18 g PUFA/kg feed and 22% PUFA in backfat, without deterioration of fresh and frozen backfat. However, for meat processing, demands could be more severe. PMID- 22060763 TI - Colon and muscle metastases from lobular breast carcinoma: a very rare entity. PMID- 22060764 TI - Comprehensive perinatal safety initiative to reduce adverse obstetric events. AB - A comprehensive perinatal safety initiative (PSI) was incrementally introduced from August 2007 to July 2009 at a large tertiary medical center to reduce adverse obstetrical outcomes. The PSI introduced: (1) evidence-based protocols, (2) formalized team training with emphasis on communication, (3) standardization of electronic fetal monitoring with required documentation of competence, (4) a high-risk obstetrical emergency simulation program, and (5) dissemination of an integrated educational program among all healthcare providers. Eleven adverse outcome measures were followed prospectively via modification of the Adverse Outcome Index (MAOI). Additionally, individual components were evaluated. The logistic regression model found that within the first year, the MAOI decreased significantly to 0.8% from 2% (p<.0004) and was maintained throughout the 2-year period. Significant decreases over time for rates of return to the operating room (p<.018) and birth trauma (p<.0022) were also found. Finally, significant improvements were found in staff perceptions of safety (p<.0001), in patient perceptions of whether staff worked together (p<.028), in the management (p<.002), and documentation (p<.0001) of abnormal fetal heart rate tracings, and the documentation of obstetric hemorrhage (p<.019). This study demonstrates that a comprehensive PSI can significantly reduce adverse obstetric outcomes, thereby improving patient safety and enhancing staff and patient experiences. PMID- 22060770 TI - Rapid evolution of fluoroquinolone-resistant Escherichia coli in Nigeria is temporally associated with fluoroquinolone use. AB - BACKGROUND: Antibiotic resistance has necessitated fluoroquinolone use but little is known about the selective forces and resistance trajectory in malaria-endemic settings, where selection from the antimalarial chloroquine for fluoroquinolone resistant bacteria has been proposed. METHODS: Antimicrobial resistance was studied in fecal Escherichia coli isolates in a Nigerian community. Quinolone resistance determining regions of gyrA and parC were sequenced in nalidixic acid resistant strains and horizontally-transmitted quinolone-resistance genes were sought by PCR. Antimicrobial prescription practices were compared with antimicrobial resistance rates over a period spanning three decades. RESULTS: Before 2005, quinolone resistance was limited to low-level nalixidic acid resistance in fewer than 4% of E. coli isolates. In 2005, the proportion of isolates demonstrating low-level quinolone resistance due to elevated efflux increased and high-level quinolone resistance and resistance to the fluoroquinolones appeared. Fluoroquinolone resistance was attributable to single nucleotide polymorphisms in quinolone target genes gyrA and/or parC. By 2009, 35 (34.5%) of isolates were quinolone non-susceptible with nine carrying gyrA and parC SNPs and six bearing identical qnrS1 alleles. The antimalarial chloroquine was heavily used throughout the entire period but E. coli with quinolone-specific resistance mechanisms were only detected in the final half decade, immediately following the introduction of the fluoroquinolone antibacterial ciprofloxacin. CONCLUSIONS: Fluoroquinolones, and not chloroquine, appear to be the selective force for fluoroquinolone-resistant fecal E. coli in this setting. Rapid evolution to resistance following fluoroquinolone introduction points the need to implement resistant containment strategies when new antibacterials are introduced into resource-poor settings with high infectious disease burdens. PMID- 22060771 TI - Antigenic specificity of monoclonal antibodies to beef myoglobin determined by cross-reactivity studies against myoglobins from domestic species. AB - Six rat monoclonal antibodies to beef myoglobin were studied to pinpoint the antigenic determinants they recognize. Their ability to bind myoglobin from beef, sheep, goat, horse, pig and chicken was compared in a competitive ELISA using biotinylated beef myoglobin. Correlation of sequence differences with relative binding allowed us to identify critical antigenic residues recognized by these antibodies. Each domain included residues previously considered not to be directly involved in the antigenic structure of myoglobin. Moreover, a possible orientation of myoglobin when adsorbed onto plastic surfaces was defined. These antibodies should be valuable tools for analysing conformational changes of the protein occurring during chemical or physical treatments. PMID- 22060772 TI - Relationship between degradation of proteoglycans and weakening of the intramuscular connective tissue during post-mortem ageing of beef. AB - Changes in proteoglycans (PGs) during post-mortem ageing of bovine m. semitendinosus were studied. Electron microscopic observations made it clear that there were two types of PGs in bovine m. semitendinosus immediately post-mortem: PGs were arranged regularly in the basement membrane and PGs associated with collagen fibrils in the perimysium. After 28 days ageing at 4 degrees C, no PG was observed in the basement membrane, and the greater part of PGs in the perimysium had disappeared. The total amount of PGs decreased with time post mortem. SDS-polyacrylamide gel electrophoresis indicated that PGs with a high molecular weight disappeared within 7 days post mortem. These results suggest that PGs are degraded during post-mortem ageing of beef. The degradation of PGs seems likely to be the main factor in the weakening of intramuscular connective tissues, i.e., separation of collagen fibrils and fibres from the endomysium and the perimysium, which results in the partial tenderization of beef during post mortem ageing. PMID- 22060773 TI - Proteolysis of type III collagen by collagenase and cathepsin B under high hydrostatic pressure. AB - The effects of high hydrostatic pressures on the kinetics of hydrolysis of type III collagen from calf skin by collagenase and cathepsin B were studied. Collagen hydrolysates sampled at different time intervals (0-90 min) and at different pressures (0.1-300 MPa) were analysed by reverse-phase high pressure liquid chromatography. The rate of collagen hydrolysis decreased up to 300 MPa for both enzymes. The rate of collagen hydrolysis with cathepsin B was drastically reduced between 0.1 and 100 MPa. Significant differences in the populations of the peptides in cathepsin B hydrolysates were observed in chromatograms corresponding to different pressures. This indicated that some amino acid side-chains were less exposed to cathepsin B recognition on the surface of collagen molecules at high pressures. In contrast, the chromatograms of collagenase hydrolysates showed similar patterns, varying only by the peak heights in chromatograms corresponding to the 0.1-300 MPa pressure range. Pressureinduced decreases of the enzyme apparent activities suggested that the activation volumes for the reaction of both enzymes were positive. PMID- 22060774 TI - Effect of low dose gamma radiation on lipids in five different meats. AB - Five types of meats were irradiated by gamma radiation up to a dose of 10 kGy. The m. longissimus dorsi from pork, lamb and beef was irradiated as well as turkey leg and turkey breast muscle. After irradiation, the lipids were extracted from the muscles to ascertain the effect of irradiation. Peroxide and iodine values along with malonaldehyde concentration were used to assess any damage made to the lipids, and to note any significant differences in these compounds due to the type of muscle tissue. Peroxide and iodine values showed that at low irradiation dose, <10 kGy, there was no significant change in any of the meat lipids. Malonaldehyde concentration changed significantly at the micromolar level due to irradiation dose, but only in turkey breast muscle. PMID- 22060775 TI - Some observations on the absorption spectra of various myoglobin derivatives found in meat. AB - The three principal myoglobin states of haem pigment, oxymyoglobin, metmyoglobin reduced myoglobin, and the ferrous nitrous oxide form, nitrosomyoglobin, were prepared as pure pigments in solution. The absorbance spectra of these solutions were determined and extinction coefficients calculated. The position of the absorption peaks showed some small differences compared to published data, in particular the use of absorbance readings at 525 nm as an isobestic point for all three could be questioned. The use of mathematical transforms to first or second difference functions showed merit for the identification of mixtures of some of the myoglobin forms. The second difference function separated the broad absorbance band in the Soret region into two separate troughs, thereby resolving a mixture of oxymyoglobin and reduced myoglobin. It is suggested that based on absorption spectra, similar mathematical transforms could be applied to the interpretation of reflectance spectra of meat and meat products. Further evaluation of such mathematical transformations is required on a range of meat reflectance spectra. PMID- 22060776 TI - The origin of the 30 kDa component appearing during post-mortem ageing of bovine muscle. AB - The most predominant component appearing on SDS-PAGE of myofibrils prepared from bovine m. vastus intermedius (VI) during ageing for 31 days post mortem at 0-2 degrees C was a component with a molecular weight of 32 kDa (SDS-32 kDa). In this study, the origin of the SDS-32 kDa component, which was thought to correspond to the 30 kDa component already known, was investigated. On the SDS-PAGE of the crude troponins, both troponin T and the 34 kDa component were gradually degraded during ageing and then troponin T disappeared at 24 days post mortem, while the concentration of the 32 kDa component showed a tendency to increase during ageing. The 32 kDa component was prepared from troponin of bovine VI muscle stored for 17 days post mortem using CM-Toyopearl chromatography, and named the native 32 kDa component. Its mobility on SDS-PAGE agreed with that of the SDS-32 kDa component. The SDS-32, native 32 and 34 kDa components were recognized by the polyclonal anti-troponin T antibody, and furthermore, the patterns of amino acid composition of both the native 32 and 34 kDa components were very similar to troponin T. Thus, it was considered that these two components would be polypeptides from the degradation of troponin T. We concluded that the SDS-32 kDa component must be derived from the degraded poly-peptides of troponin T. However, it still remains a possibility that some degradation products from other myofibrillar proteins are included in the SDS-32 kDa component. Therefore, further studies about the identity of this component will be required. PMID- 22060777 TI - Polyclonal antibodies against protein F from the cell envelope of Pseudomonas fluorescens for the detection of psychrotrophic bacteria in refrigerated meat using an indirect ELISA. AB - An indirect enzyme-linked immunosorbent assay (ELISA) has been developed for detection of Pseudomonas fluorescens and related psychrotrophic bacteria in refrigerated meat. The ELISA uses polyclonal antibodies raised in rabbits against protein F from the cell envelope of Pseudomonas fluorescens AH-70. The anti protein F antibodies were recovered from the crude antiserum by ammonium sulfate precipitation and conjugated to biotin. Commercial Extr Avidin-peroxidase conjugate was used to detect the biotinylated antibodies bound to their specific antigens. Subsequent enzymatic conversion of substrate gave distinct absorbance differences when assaying meat samples containing P. fluorescens strains of different origin as well as related psychrotrophic microorganisms. The detection threshold for the ELISA assay developed in this work was 10(4)-10(5) cfu cm(-2). PMID- 22060778 TI - Physical characteristics of lamb primals packaged under vacuum or modified atmospheres. AB - Lamb primals (shoulders) were packaged under vacuum, 80% O(2)/20% CO(2), 50% CO(2)/50% N(2) or 100% CO(2) and stored at 5 or 0 degrees C. Pack contents were examined at 7 day intervals to determine the composition of the pack atmosphere, drip loss, colour (muscle and fat) and pH (surface and internal). The composition of the gas atmospheres changed very little during storage. The only significant differences between developed head space compositions above primals stored at the two different temperatures (5 and 0 degrees C) were noted in packs stored for 28 days under 80% O(2)/20% CO(2). Low levels of drip loss (<0.5%) were noted in all packs stored under the modified gas atmospheres. In contrast, significantly higher levels of drip loss (0.5-1.1%) were noted in vacuum packaged lamb stored at 5 and 0 degrees C. Acceptable muscle colour was observed 2 hr after opening of all packs. The only significant differences between atmospheres for lean muscle colour were noted after 28 days storage. Fat colour did not generally change during storage in any of the atmospheres, apart from a slight bleaching effect at 7 days. There were no significant differences between the surface or internal pH values noted after storage under any of the atmosphere/temperature combinations. In general, higher pH values were observed at the surface of the meat than in the interior. This pattern was noted before and after storage. PMID- 22060779 TI - Frozen storage of Bologna sausages as a function of fat content and of levels of added starch and egg white. AB - The effect of freezing and frozen storage on the water holding capacity (WHC) and texture of Bologna sausages formulated with varying fat levels (7.2, 12.8 and 20.1%) and with different proportions of added starch (0, 5 and 10%) and egg white (EW) (0, 1.5 and 3%) was studied. High-fat sausages exhibited better binding properties than low-fat sausages. Freezing and frozen storage caused binding properties to deteriorate, the more so the lower the fat content. In general, addition of starch caused an increase in penetration force and a decrease in elasticity of sausages, and also favoured freeze-thaw stability. Addition of egg white had no influence (p > 0.05) on the WHC of Bologna sausages but did influence texture. PMID- 22060780 TI - Effect of protective cultures and packaging film permeability on shelf-life of sliced vacuum-packed cooked ham. AB - Cooked ham produced with Lactobacillus alimentarius and Staphylococcus xylosus as protective cultures, and control ham were sliced, vacuum-packed in pouches with oxygen transmission rates (OTR) of 360 and 77 cm(3)/m(2)/24 hr/atm, and stored at 4 degrees C in the dark. The addition of protective cultures increased (p < 0.05) lactic acid bacteria and micrococci and staphylococci counts in the meats. After cooking, the population of lactic acid bacteria was higher (p < 0.05) in hams produced with L. alimentarius than the other treatments. Protective cultures increased (p < 0.05) the shelf-life of cooked ham. The higher the OTR, the lower the shelf-life. Cooked ham with L. alimentarius was acceptable up to 28 days compared to control ham with a shelf-life of 3 weeks. Micrococci and staphylococci were inhibited in hams with L. alimentarius. Hams with S. xylosus had a better red colour than other treatments. Cooked hams with protective cultures had lower total aerobic bacteria, micrococci and staphylococci and Brochothrix thermosphacta counts than control hams which had higher populations of lactic acid bacteria and lower pseudomonads. PMID- 22060781 TI - Changes in colour of beef m. longissimus dorsi muscle during ageing. AB - The effects of vacuum packaging, chilling rate (slow or fast), and fat cover thickness (?4 mm or 7-8 mm) on the colour parameters of beef m. longissimus dorsi muscle were assessed during ageing. The m. longissimus dorsi muscle was aged on the carcass or in vacuum packaging. Muscle samples for analysis were taken on days 0 (24 hr post mortem), 2, 4, 8, 12 and 16 to ascertain the parameters. Ageing time influenced all colour parameters, while chilling rate affected lightness ('L'), yellowness ('b'), and hue angle difference (HD), and fat cover thickness influenced 'L' and 'b' only. PMID- 22060782 TI - Collagen cross-linking in porcine m. longissimus lumborum: Absence of a relationship with variation in texture at pork weight. AB - The determination of all currently known intermolecular cross-links present in intramuscular collagen of porcine m. longissimus lumborum is described in relation to the texture of the meat as determined both objectively by instrumentation and subjectively by sensory panel. The variation in texture observed in the m. longissimus lumborum of pork weight pigs has been shown to be unrelated to the total collagen content or to the nature of the collagen intermolecular cross-links. We have also demonstrated a considerable error in the colorimetric method for quantitation of hydroxyproline when determining the very low values of collagen present in pig meat. During this study we have established a sound protocol for the determination of all the known cross-links in intramuscular collagen of meat from any meat animal species. PMID- 22060783 TI - Estimation of the muscle to bone ratio of the bovine pelvic limb using a morphometric method Laville, E., Astruc, T., Martin, V. & Bousset, J. (1995). Meat Sci., 41(3), 345. PMID- 22060784 TI - Soyasaponin Ab ameliorates colitis by inhibiting the binding of lipopolysaccharide (LPS) to Toll-like receptor (TLR)4 on macrophages. AB - Many clinical studies have shown that daily intake of soybean [ Glycine max (L.) Merr., Fabacease] or its foods may reduce the risk of osteoporosis, heart attack, hyperlipidemia, coronary heart disease, cardiovascular and chronic renal diseases, and cancers, including prostate, colon, and breast cancers. Of the soy constituents, soyasaponins exhibit anti-aging, antioxidant, apoptotic, and anti inflammatory effects. However, the anti-inflammatory effect of soyasaponin Ab has not been thoroughly studied. Therefore, we investigated its anti-inflammatory effects in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice and lipopolysaccharide (LPS)-stimulated peritoneal macrophages. Soyasaponin Ab inhibited colon shortening, myeloperoxidase activity, the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), and activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Soyasaponin Ab (1, 2, 5, and 10 MUM) inhibited the production of NO (IC(50) = 1.6 +/- 0.1 MUM) and prostaglandin E(2) (IC(50) = 2.0 +/- 0.1 ng/mL), the expression of tumor necrosis factor (TNF)-alpha (IC(50) = 1.3 +/- 0.1 ng/mL), interleukin (IL)-1beta (IC(50) = 1.5 +/- 0.1 pg/mL), and toll-like receptor (TLR)4, and the phosphorylation of interleukin-1 receptor-associated kinase (IRAK)-1 in LPS stimulated peritoneal macrophages. Soyasaponin Ab weakly inhibited the phosphorylation of ERK, JNK, and p38. Soyasaponin Ab significantly reduced the binding of Alexa-Fluor-594-conjugated LPS to peritoneal macrophages. Soyasaponin Ab did not affect TLR4 expression or LPS-induced NF-kappaB activation in TLR4 siRNA-treated peritoneal macrophages (knockdown efficiency of TLR4 > 94%). On the basis of these findings, soyasaponin Ab may ameliorate colitis by inhibiting the binding of LPS to TLR4 on macrophages. PMID- 22060785 TI - Enzymatic assay to determine collagen thermal denaturation and solubilization. AB - Analysis of collagen in fresh and cooked meat products typically separates the heat-solubilized portion from the insoluble. However, extensive changes in the insoluble portion can occur during heat treatment that greatly affect cooked meat texture. This study evaluated a method of determining the proportion of solubilized and heat-altered collagen using a nonspecific protease from Streptomyces griseus to digest heat-altered collagen. Bovine semitendinosus muscle was heated to either 50, 60, or 70 degrees C. Warner-Bratzler shear forces, Ringer's-soluble and insoluble collagen, and enzyme-labile collagen (digested with pronase) were determined on all samples. The enzyme-labile fraction (ELF) increased as endpoint temperature increased, and a corresponding decrease occurred in the total unaltered fraction (TUF). The Ringers-soluble fraction (RSF) increased slightly. Correlations of peak shear force and peak energy with TUF (0.65 and 0.81) were stronger than those with RSF (0.53 and 0.57). Use of this method should provide further insights into the role of collagen in the development of cooked meat texture. PMID- 22060786 TI - Fatty acid composition of goat diets vs intramuscular fat. AB - Twenty Boer x Spanish goats, at the age range of 90-118 days, were assigned to two dietary treatments, with 10 animals fed a grain ration (G) and the other 10 grazed in rangeland. The grain ration contained sorghum grain (67.5%), cottonseed hulls, dehydrated alfalfa meal, cottonseed meal, soybean meal, molasses, and mineral and vitamin supplements. Animals were slaughtered at the age range of 206 234 days. Intramuscular fat (IF) and the diet specimens - representative samples of G and the parts of range plants (RPs) that goats were expected to have consumed - were analyzed for fatty acid composition. The percentage of 16:0 was higher in RPs than in G, but not different between IF from range goats and that from grain-fed goats. Total unsaturated fatty acid (UFA) percentage was higher in G than in RPs. The major UFAs were 18:2 and 18:3 in RPs, and 18:1 and 18:2 in G. In IF, 18:1 constituted more than two-thirds of UFAs, regardless of diet type. PMID- 22060787 TI - Training for more accurate visual fat estimation in meat. AB - Much animal fat in the diet is contained in meat. As fat intake is considered too high in western societies, a more fat-conscious attitude may be desirable. One of the parties involved is the butcher, who sells fresh meat directly to the consumer. In a pre-post experimental design, with an interpolated training phase, the possibility to improve the ability of student butchers to visually estimate fat content of meat, was investigated. A limited number of training sessions, in which immediate feed-back was given of the actual fat percentage after each estimation, led to a large improvement in fat estimation accuracy. A delayed post test indicated that most of the training effect was preserved after six weeks. Similarities between the observed learning process and informational feed-back learning with numerosity stimuli were discussed. On the basis of these results it is recommended that courses for trainee butchers include a short course on fat estimation in their curriculum. If butchers sell what they think they sell, consumers are more likely to get what they think they get. Increased 'fat awareness' may indirectly contribute to healthier eating habits. PMID- 22060788 TI - Interrelationships between descriptive texture profile sensory panel and descriptive attribute sensory panel evaluations of beef Longissimus and Semitendinosus muscles. AB - The objectives of our study were to examine the relationships between highly trained and experienced descriptive texture profile (DTP) sensory panel and trained descriptive attribute (DA) sensory panel evaluations, and to evaluate the effects of muscle fiber orientation on sensory panel tenderness scores of beef longissimus lumborum (LL) and semitendinosus (ST) muscles. Eighteen LL and 18 ST muscles were cut into 2.54 cm steaks and cooked to 71 degrees C; then 1.27*1.27*2.54-cm cubes were removed using two methods (parallel with the muscle fiber orientation and perpendicular to the steak cut surface) and presented to the two sensory panels. Both panels detected differences among replications (muscles from different carcasses); however, a panelist * replication effect occurred for the DA sensory panel. Both panels detected differences (p<0.05) in LL muscle fiber orientation for most attributes related to tenderness; however, few differences were detected for flavor and juiciness traits for either muscle. Numerous significant (r ? 0.50 or ? -0.50) correlations occurred between DTP and DA panel attributes and were generally higher when cubes were cut perpendicular to the steak cut surface. The DTP panelists were more consistent in their evaluations of texture attributes; however, they were more sensitive to muscle fiber orientation. Both panels were effective in detecting differences among replications. PMID- 22060789 TI - Evolution of volatile aldehydes in Iberian ham matured under different processing conditions. AB - To evaluate the influence of the Iberian ham processing conditions in the evolution of volatile aldehydes, 35 hams were processed in two plants following different conditions of relative humidity and temperature. For this, free fatty acids, peroxide values and volatile aldehydes were quantified in the hams. The highest increases in free fatty acids were noted during the drying stage in both processing plants. The drying period also revealed the greatest increase in peroxide values, where the highest values were in those hams processed at higher temperatures. The temperature during post-salting and drying had a marked influence on the formation of volatile aldehydes, being responsible for the differences in volatile compounds of matured hams. PMID- 22060790 TI - Fatty acid composition and sensory characteristics of lamb carcasses from Britain and Spain. AB - Fatty acid composition of intramuscular fat in M. Longissimus was measured in four groups of lambs representing two Spanish breeds: Rasa Aragonesa (RA) and Merino (ME) and two British lamb types: the Welsh Mountain breed (WM), whose carcasses were purchased in Spain and typical early lambs (EL) purchased in Britain. The lambs grown in Spain were concentrate fed and slaughtered at a lighter weight and lower age than those grown in Britain. The British lamb carcasses purchased in Spain were of a similar weight to the Spanish lambs but were lighter than the lamb carcasses purchased in Britain. The British lambs were grass fed. Relationships between fatty acid (FA) composition and sensory attributes were examined following sensory testing of all lambs by both British and Spanish taste panels. The production system was shown to be more important than breed in determining FA composition. British lambs had higher percentages, within total fatty acids, of 18:0, 18:3 (n-3) and long chain polyunsaturated n-3 FA and lower percentages of 18:2 (n-6) and long chain polyunsaturated n-6 FA than Spanish lambs. These differences were due to the different feeding systems used. The amounts of these FA in muscle (mg/100 g) were also different between the British and Spanish groups, not only because the British lambs had more total fat. For both taste panels, odour and flavour intensity were positively correlated with the amounts and percentages of 18:0 and 18:3 and negatively correlated with those of 18:2. This was explained by the fact that both panels gave higher odour and flavour intensity scores to the grass-fed British lamb with high 18:3 levels and lower scores to the concentrate-fed Spanish lamb with high 18:2 levels. However, 18:0 and 18:3 were positively correlated with flavour quality and overall appraisal for the British panel and negatively for the Spanish panel. Conversely, 18:2 was a positive contributor to flavour and overall preference for the Spanish panel and was negative for the British panel. The results show that the production system affects muscle fatty acid composition and the flavour of lamb. However, people's preference is determined to a large extent by their past experience. PMID- 22060791 TI - The effect of selection for growth rate on carcass composition and meat characteristics of rabbits. AB - The effect of selection for growth rate on carcass composition and meat quality was assessed by comparing two groups of rabbits belonging to different generations of a selection experiment. A Bayesian approach was used. Embryos belonging to generations 3 and 4 of selection were frozen and thawed to be contemporary of animals from generation 10. A control group (C), formed from offspring of these embryos, was contemporary to offspring of generations 10 and 11 of selection, chosen at random, which constituted the selected group (S). One hundred and thirty-one contemporary rabbits were slaughtered at approximately the Spanish commercial live weight of 2 kg. Carcasses were dissected and measured according to the norms of the World Rabbit Scientific Association. An animal model including effects of genetic group (C, S) and sex, and slaughter weight as a covariate was used. S animals had a higher development of liver, kidneys and of a set of organs consisting of the thymus, trachea, oesophagus, lung and heart, relative to C. For dissectible fat, S animals had less than C: -0.31 g for scapular fat, -1.62 g for perirenal fat and -2.03 g for inguinal fat. S had a lower content (-0.39%) of dissectible fat percentage in the "Reference" carcass, indicating a lower degree of maturity at slaughter. The meat to bone ratio was not affected by selection, but the meat and bone contents of the hind leg were 3.25 and 0.71 g higher, respectively, in the C group. Selected animals had a lower water holding capacity in the raw meat (-2.10%), a higher water holding capacity in the cooked meat (2.17%), a higher cooking loss (3.31%) and a lower fat percentage in the meat of a hind leg (-0.37%). Females had more fat than males: 0.26 g for scapular fat, 1.02 g for perirenal fat, 1.10 g for inguinal fat, and 0.24% for total dissectible fat percentage of the "Reference" carcass. PMID- 22060792 TI - High pressure/thermal treatment of meat batters prepared from freeze-thawed pork. AB - Various meat batters were prepared from pork subjected to different freeze-thaw cycles. These batters were pressurized (300 MPa, 30 min) at low, non-denaturing temperature (10 degrees C) followed by heating (70 degrees C) (PLT+H) and at high, denaturing temperature (70 degrees C) (HUPC). Nonpressurized (NP), heated only (70 degrees C) sample were also produced. Freezing of meat influenced water binding and textural properties of meat batters; the influence on texture was affected by thermal and pressure conditions. Pressure prior to heating produced a coarse, irregular and loose protein matrix, favoring the formation of weaker gel structures than were found in non-pressurized samples. Pressurization at denaturing temperatures reduced the level of protein denaturation induced by the thermal treatment. The resulting gel structures had better water binding properties but were weaker than non-pressurized samples and samples pressurized prior to heating. PMID- 22060793 TI - Buffalo meat as a salted and cured product. AB - Bresaola, a GPI product, is produced by salting and curing different cuts of the hindquarters of lean bovine meat. The use of buffalo meat to produce similar processed, cold-cut products demonstrated the possibility of transforming cuts of buffalo rump into a product similar to that of beef, even considering parameters that penalise the buffalo product like tenderness and colour. PMID- 22060794 TI - Evaluation of a DNA fingerprinting method for determining the species origin of meats. AB - This study describes an investigation into the use of a PCR-RFLP technique as a routine analytical tool for species testing. The technique was used to generate DNA fingerprints for 22 animal species by amplifying a 359 bp region within the cytochrome b gene and digesting the amplified product using Hae III and Hinf I. All species could be discriminated using the two restriction enzymes with the exception of kangaroo and buffalo. Cooking the tissues did not affect the DNA extractions or the profiles generated. When mixtures were investigated, pig was preferentially amplified and dominated over all species tested, even at levels of 1%. Another set of cytochrome b primers which amplified 464 bp, was also tested for the analysis of these mixtures. Beef was found to be favourably amplified over the other species. Anomolous results where the digested products exceeded 359 bp was also investigated. Co-amplification was found to occur in the species investigated. Results of this study suggest that the CytB PCR-RFLP method shows promise for the identification of both cooked and uncooked tissues, although the method is unsuitable for analysing meat mixtures. PMID- 22060795 TI - Influence of supranutritional vitamin E and copper on alpha-tocopherol deposition and susceptibility to lipid oxidation of porcine membranal fractions of M. Psoas major and M. Longissimus dorsi. AB - Addition of 200 ppm all-rac-alpha-tocopheryl acetate to pig feed supplemented with 6% high-oleic rapeseed oil gave mitochondrial membranes, which had a lower rate of formation of free radicals as determined by ESR-spectroscopy using the spin-trapping technique. Addition of 175 mg/kg copper to the feed, with or without all-rac-alpha-tocopherol acetate addition was not pro-oxidative (or anti oxidative). While these effects were similar for both the oxidative M. Psoas major (PM), and the glycolytic, M. Longissimus dorsi (LD), differences between muscles were characterised by a higher activity of beta-hydroxyacyl-coenzyme A dehydrogenase (HAD) and citrate synthase (CS), and a lower activity of lactate dehydrogenase (LDH) in PM than in LD (p<0.001). The concentration of alpha tocopherol in muscles, liver, and plasma was influenced by the alpha-tocopherol level in the feed (p<0.001). The concentration of fatty acids in microsomes was not influenced by dietary treatments, but was higher in PM than in LD. However, the total concentration of fatty acids in the mitochondria of PM was higher in pigs supplemented with all-rac-alpha-tocopheryl acetate. PMID- 22060796 TI - Stability of catalase and its potential role in lipid oxidation in meat. AB - The activity of catalase in microbial growth-controlled and uncontrolled ground beef muscle (semimembranosus, SM) did not change (P>0.05) during 6-day storage at 4 degrees C. Likewise, catalase activity in ground, beef SM and longissimus dorsi (LD), pork LD, and chicken breast (B) and thigh (T) muscles was not affected (P>0.05) by 2-month storage at -20 degrees C, with or without mid-month thawing/refreezing. When sodium azide (a catalase inhibitor) was added to ground beef SM, lipid oxidation (as measured by peroxide values) during 4-day refrigeration was higher (P<0.05) in treated samples - 43 and 55% higher at day 2 and day 4, respectively - than in the controls. It was concluded that catalase would be stable during meat storage/distribution and contribute significantly to the antioxidative process in raw meat products. PMID- 22060797 TI - Colour of normal and high pH beef heated to different temperatures as related to oxygenation. AB - The effects of oxygenation and thermal treatment (internal temperature, T(i): 45, 60, 75 degrees C) on the colour and some colour related physical and biochemical properties of beef longissimus dorsi (LD) muscle, both normal (pH(u)~5.6) and DFD (pH(u)>6.6), were studied. The colour components (L (*), a (*), b (*) values) for the raw and heated LD, both before and after oxygenation, were instrumentally and sensorily evaluated. The colour of raw and heated (60 degrees C) DFD beef before and after oxygenation differed significantly from the normal meat and contained more native muscle pigment (TMP). pH also influenced the depth of the oxygenated layer, specific activity of cytochrome c oxidase (SACCO) and the amount of oxygen consumed. An increase in internal temperature was usually accompanied by a lower SACCO and a significant decrease of TMP, as well as a change of all colour parameters. Oxygenation of the raw and heated slices (except at 75 degrees C) of both types of meat led to higher L (*), a (*) and b (*) values. PMID- 22060798 TI - Effect of residual oxygen on colour stability during chill storage of sliced, pasteurised ham packaged in modified atmosphere. AB - The critical level of residual oxygen to avoid light induced oxidative discoloration during chill storage of sliced, pasteurised ham packaged in modified atmosphere (20% carbon dioxide balanced with nitrogen in a 1:3 product to headspace volume ratio) was found to lie between 0.1 and 0.5% oxygen. In 0.5% oxygen light induced discoloration was significant, as detected by the tristimulus colorimetry redness parameter, when compared to the same product stored in the dark, while at 0.1 and 0.02% oxygen the colour was stable both in the dark and when exposed to light for up to 27 days in chill storage. Lipid oxidation, determined as 2-thiobarbituric acid-reactive substances, and total plate counts showed no difference between discoloured and colour stable products, although a trained panel in a triangle test could differentiate between the taste of ham from packages with 0.02 and 0.5% oxygen after 27 days of chill storage. PMID- 22060799 TI - Survival of enterohaemorrhagic Escherichia coli O157:H7 strain in Turkish soudjouck during fermentation, drying and storage periods. AB - Soudjouck (a kind of Turkish sausage) batter was inoculated with Escherichia coli O157:H7 at a level of 10(5) colony-forming unit (CFUg) and kept overnight at 4 degrees C. After stuffing the soudjouck batter into natural casing, fermentation was carried out at 24+/-2 degrees C and 90-95% relative humidity (RH) for 3 days with subsequent drying at 22+/-2 degrees C and 80-85% RH for 5 days. Then, half of soudjouck samples were vacuum-packed in polyethylene bags and the rest were kept open. All samples were stored at 4 degrees C (55% RH) for 3 months. E. coli O157:H7 and lactic acid bacteria counts, moisture contents and pH values of the samples were determined during fermentation, drying and storage periods. Results showed that count of E. coli O157:H7 decreased by 3 log unit during fermentation and drying periods. It was observed that this pathogen survived longer in vacuum packaged samples (more than 2 months) than non-vacuum samples (more than 1 month). PMID- 22060800 TI - Conversion to low transfusion-related acute lung injury (TRALI)-risk plasma significantly reduces TRALI. AB - BACKGROUND: Transfusion-related acute lung injury (TRALI) is an uncommon but serious transfusion reaction. Studies have shown that the transfusion of HLA and HNA antibodies in donor plasma can lead to TRALI. Female donors are more likely to have such antibodies due to alloantigen exposure during pregnancy. Many blood suppliers have now implemented various TRALI risk reduction strategies to unknown effect. A retrospective analysis of TRALI reactions in plasma recipients before and after the conversion to low-TRALI-risk plasma (all-male donor plasma, male predominant plasma, nulliparous female plasma, and HLA antibody-tested plasma) is reported. STUDY DESIGN AND METHODS: Transfusion reaction reports at three large hospitals 16 months before and 16 months after the conversion to low-TRALI-risk plasma were analyzed. Respiratory reactions were categorized as TRALI, possible TRALI, or other (e.g., transfusion-associated circulatory overload or allergic reactions). Reactions were reported as a percentage of total units transfused and rates for the two time periods were compared. Trends in reaction rates for other components were also compared. RESULTS: A total of 2156 transfusion reactions in association with 461,598 transfused blood components were reviewed. The incidence of combined TRALI or possible TRALI reactions, due to the transfusion of plasma, decreased from 0.0084% to zero (p = 0.052). The rate of TRALI or possible TRALI reactions in red blood cell and platelet recipients did not change significantly. CONCLUSION: The conversion to low-TRALI-risk plasma has reduced the incidence of TRALI reactions in plasma recipients. PMID- 22060801 TI - Gender differences in early maladaptive schemas in a treatment-seeking sample of alcohol-dependent adults. AB - The current study examined early maladaptive schemas among alcohol-dependent men and women and sought to determine whether men and women differed in their early maladaptive schemas. Using preexisting patient records of adults diagnosed with alcohol dependence from a residential treatment center in the Southeastern United States, from 2005 to 2010 (N = 854), results showed that women scored significantly higher than men on 14 of the 18 early maladaptive schemas assessed. Both women and men endorsed having a number of early maladaptive schemas, with four schemas being particularly prevalent across gender. Study limitations are noted and implications of these findings for treatment and future research are discussed. PMID- 22060802 TI - Evaluation of 1,5-anhydroglucitol, hemoglobin A1c, and glucose levels in youth and young adults with type 1 diabetes and healthy controls. AB - BACKGROUND AND OBJECTIVE: Serum 1,5-anhydroglucitol (1,5-AG) is a marker of hyperglycemic excursions in adults with diabetes and hemoglobin A1c (HbA1c) < 8%. We compared 1,5-AG levels among youth and young adults with and without type 1 diabetes (T1D) and investigated the utility of 1,5-AG in the assessment of glycemic status in pediatric T1D. METHODS: We compared 1,5-AG, HbA1c, and plasma glucose levels in 138 patients with T1D (duration >=1 yr) and 136 healthy controls, aged 10-30 yr. Within each group, we investigated associations between 1,5-AG and clinical characteristics, HbA1c and random plasma glucose. For patients with T1D, 1,5-AG was further analyzed according to HbA1c strata: <8, 8 9, and >9%. RESULTS: Compared to controls, patients with T1D had higher HbA1c (8.5 +/- 1.6 vs. 5.1 +/- 0.4%, p < 0.0001), lower 1,5-AG (4.0 +/- 2.0 vs. 24.7 +/ 6.4 ug/mL, p < 0.0001), and higher glucose (11.1 +/- 5.2 vs. 5.1 +/- 0.9 mmol/L, p < 0.0001). Males had higher 1,5-AG than females within patients (4.5 +/- 2.3 vs. 3.4 +/- 1.6 ug/mL, p = 0.003) and controls (26.0 +/- 6.6 vs. 23.5 +/- 6.0 ug/mL, p = 0.02). 1,5-AG was not correlated with glucose in either group. 1,5-AG was significantly correlated to HbA1c in patients, but not controls. For patients with HbA1c < 8%, 1,5-AG demonstrated the widest range and was not predicted by HbA1c; 1,5-AG levels were narrowly distributed among patients with HbA1c >= 8%. CONCLUSIONS: Youth and young adults with T1D demonstrate similar 1,5-AG levels which are distinct from controls. 1,5-AG assessment may provide unique information beyond that provided by HbA1c in the mid-term assessment of glycemic control in young patients with T1D and HbA1c < 8%. PMID- 22060803 TI - Possibilities for predicting taste and tenderness of broiled beef steaks using an optical-electromechanical probe. AB - A prototype beef-quality probe was tested on 47 strip-loin steaks evaluated by a sensory panel. The probe responded to the reflectance or back-scatter of initially polarized light from 400 to 800 nm, UV fluorescence of connective tissue, and electromechanical resistance to needle penetration. All three indicators contributed to predictions (p < 0.01) of tenderness (r = 0.58 for initial tenderness after 3 days aging, r = 0.57 for sustained tenderness at 3 days, r = 0.42 for initial tenderness at 21 days, and r = 0.58 for sustained tenderness at 21 days) and taste (r = 0.59 for flavor intensity at 3 days, r = 0.41 for beef flavor at 3 days, and r = 0.41 for flavor intensity at 21 days). The reflectance of initially polarized light from 440 to 600 nm appeared to contain a relatively high content of useful information, but further improvements to the prototype are required to obtain more reliable predictions for industrial use. PMID- 22060804 TI - The effect of two handling and slaughter systems on skin damage, meat acidification and colour in pigs. AB - In order to minimize the high proportion of carcass and meat quality defects recorded in commercially slaughtered pigs, the optimum handling, stunning and bleeding-out conditions must be implemented. In this study improvements in pig handling resulted in the elimination of electric goading within the raceways, which reduced the skin blemish score by 50%. Furthermore, the application of higher stunning voltage (200 V) and the immediate bleeding-out in the prone position improved the post-mortem acidification rate in the Longissimus thoracis (LT) and Semimembranosus (SM) muscles. This resulted in a sharp reduction of the PSE incidence in both muscles. A positive effect on muscle metabolism was also showed by the lower release of CPK into the bloodflow. These results show that, under commercial conditions, the design of slaughter handling systems and the slaughter procedures can have an effect on skin damage and on the quality of the pig meat. PMID- 22060805 TI - Optimizing the traditional processing of beef into Kilishi. AB - Kilishi, a meat-based traditional product of Sahelian Africa, is a sun-dried, coated and grilled beef. The effect of moisture content of the dried meat before coating and sauce ingredients, on coating quality and product yield of kilishi were determined. Analysis of the losses after the coating and grilling stages highlighted the mechanisms that determine coating quality. To improve sauce adhesion to the dried meat, wheatflour was added to the traditional sauce (a mixture of groundnut paste, water, and spices). The amounts of water and wheat flour required to ensure that the sauce adhered to the meat well were also determined. This has optimized the kilishi processing to improve product yield. PMID- 22060806 TI - A note on the muscle, fat and bone contents of Portuguese light lamb carcasses. AB - A total of 72 lambs weighing between 10.1-13.0 kg (category C of the European Union grading for light lambs) from the Bragancano, Campanico, Merino Branco, Merino Preto e Serra da Estrela breeds were studied. These breeds represent 66.8% of the Portuguese sheep population. Evaluations were made at the same subcutaneous fat contents in the carcass (88.5 g kg(-1)). Small, significant (p < 0.05) differences in the range of muscle and bone contents were found; the ranges being 30 and 25 g kg(-1), respectively. These variations led to significant diferences in the muscle:bone ratios, the highest value being 3.30 and the lowest 2.73. Significant differences were also found in the content of higher-priced joints (leg + chump, loin + ribs and anterior ribs) and in the proportion of kkcf (9 g kg(-1)). No significant differences were found in the content of total fat [subcutaneous, intermuscular and kidney knob and channel fat (kkcf)] and in the muscle: total fat ratios. PMID- 22060807 TI - Simultaneous addition of Palatase M and Protease P to a dry fermented sausage (Chorizo de Pamplona) elaboration: Effect over peptidic and Lipid fractions. AB - The effect of the simultaneous addition of a lipase (Palatase M 200L Novo Nordisk A/S) and a protease (Protease P 31.000 Solvay Enzymes GMBH&CO.KG) to the manufacture of a Spanish dry fermented sausage (Chorizo de Pamplona) was studied. In relation to the free aminoacid fraction, significative increases in Glu, His, Lys, Ser, Ala, Pro, Val, Met, Ile, Leu and Phe were found. Smaller differences were observed in the aminoacids obtained from peptides. The addition of the lipase caused significant increases in palmitic, oleic and linolenic acids. Despite the observed changes, no differences were found in the sensory quality compared with the control, except for a slight softening. PMID- 22060808 TI - Effect of anatomical location on the composition of fatty acids in double-muscled Belgian Blue cows. AB - Double-muscled cows of the Belgian Blue breed, ranging from ca. 680 to 880 kg live weight were slaughtered and various fat depots sampled for lipid analysis. Subcutaneous fat (SCF), intermuscular fat in m. serratus (IMF1) and m. transversalis (IMF2), kidney fat (KF) and intramuscular fat in m. longissimus thoracis (IMF3) were sampled. In IMF3 samples, polar lipids were separated from other lipid classes by thin layer chromatography. Both the proportions (w w %) and gravimetric concentrations (mg g(-1) of sample) of long-chain fatty acids were determined in total lipids of SCF, IMF1, IMF2, KF and in lipid classes of IMF3 by gas chromatography. The greatest concentration of total fatty acids was found in KF (777.6 +/- 82.6 mg g(-1)), followed by SCF (721.3 +/- 92.2 mg g(-1)), IMF2 (709.8 +/- 72.5 mg g(-1)) and IMF1 (682.1 +/- 71.6 mg g(-1)). Triacylglycerol and polar lipid fatty acid content of m. longissimus thoracis (IMF3) were respectively 8.1 +/- 3.3 and 3.1 +/- 0.6 mg g(-1). Fatty acid content, particularly the triacylglycerol fatty acid content in IMF3, increased (p < 0.01) with increasing carcass fat content. Polar lipid fatty acids in IMF3 contained a higher proportion of polyunsaturated fatty acids (32.6 +/- 4.8 %) and lower proportion of saturated fatty acids (27.4 +/- 5.0%) compared to the triacylglycerol fatty acid fraction (p < 0.01), which may reflect a prerequisite for proper membrane functioning. Internal fat depots were more saturated (p < 0.01) compared to SCF. The proportion of monounsaturated fatty acids differed (p < 0.01) between IMF1 and IMF2, possibly reflecting differences in muscle activity and functioning. Oleic (C18:1) and stearic (C18:0) acids comprised more than 60% of the total fatty acids in all anatomical locations. PMID- 22060809 TI - Determination of sensory, chemical and cooking characteristics of retail beef cuts differing in intramuscular and external fat. AB - Top loin (TLS), top sirloin (TSS), and eye of round (EYS) steaks, and loin end (LRR) and blade end (BRR) rib, and eye of round (EYR) roasts were used to determine the effect of USDA quality grade, Choice or Select, external fat trim level, and internal temperature endpoint on sensory, chemical and cooking characteristics. Cuts cooked with external fat required slightly greater cooking times and had higher fat content in the lean than cuts cooked without external fat (p < 0.05). Regardless of quality grade or external fat trim, increasing internal temperature endpoint resulted in tougher, drier cuts with longer cooking times and greater cooking loss (p < 0.05). Choice TLS, TSS and LRR were higher (p < 0.05) in palatability than Select, but quality grade did not affect palatability of BRR, EYS or EYR. PMID- 22060810 TI - Colour-stabilising effect of muscle vitamin E in minced beef stored in high oxygen packs. AB - Minced beef samples stored in high oxygen modified atmosphere packs (80% O(2):20% CO(2)) were evaluated for colour stability during refrigerated storage. The oxymyoglobin content and surface redness (Hunter 'a' value) of m. biceps femoris samples, previously frozen and minced, were significantly lower in samples with a mean vitamin E (alpha-tocopherol) content of 2.5 MUg g(-1) compared with samples with 3.3, 3.9 or 5.5 MUg g(-1) after 4, 6 and 8 days of storage at 4 degrees C. Lipid oxidation was significantly higher in the beef samples with the low vitamin E content compared with the other groups indicating that a likely mechanism for the colour-stabilising effect of vitamin E is through its action as a lipid antioxidant. PMID- 22060811 TI - Preparation of surimi-like extract from beef hearts and its utilisation in frankfurters. AB - Surimi-like material was prepared from beef heart and evaluated in commercial frankfurter (30% fat) recipes at levels of 3, 7 10 and 15% by weight replacing lean meat. The addition of the heart surimi at a 15% level reduced (p < 0.05) cook loss compared with the control (6.4% vs 7.5%). Shear force measurements on frankfurters showed that the control had the highest value (20.4 N(-1) g) and the 15% surimi treatment the lowest (p < 0.05) value (13.9 N(-1) g). Correspondingly, sensory analysis indicated that as the surimi-type material was added the tenderness increased (p < 0.05). Panellists found no off-flavours and all the treatments scored similarly to the control in terms of overall flavour. In terms of 'overall acceptability' panellists found treatments containing 7 and 10% heart surimi were preferable to the control. Surimi-type material from hearts can be used in frankfurter formulations up to 15% without impairing texture or flavour. PMID- 22060812 TI - Immunolocalisation of intermediate filament proteins in porcine meat. Fibre type and muscle-specific variations during conditioning. AB - Two intermediate filament proteins, desmin and vinculin, were immunofluorescently localised in porcine longissimus dorsi(**) and iliocostalis muscles up to 7 days post mortem. Changes in tenderness of the m. longissimus and the water-holding capacity of both muscles were also monitored throughout this storage period. Longissimus muscle shows a rapid decline in the overall intensity of labelling for both desmin and vinculin. In contrast to the vinculin labelling, desmin labelling is preferentially lost from type IIB muscle fibres in the longissimus muscle. In the redder iliocostalis muscle, the loss of desmin and vinculin labelling was less rapid and did not show an obvious relation to muscle fibre type. In one sample with very high water loss, there were indications of greater extracellular space development and delayed loss of intermediate filament labelling. The time course of diminishing intermediate filament labelling is consistent with previous suggestions that degradation of these proteins is involved in post-mortem conditioning. The variations within and between muscles shown here may explain some of the variability in their mechanical properties. Additionally, it is suggested that intermediate filament integrity is necessary for the expulsion of water from the muscle cells during drip formation. PMID- 22060813 TI - Meat speciation by restriction fragment length polymorphism analysis using an alpha-actin cDNA probe. AB - Classical DNA fingerprinting is based on separation of DNA restriction fragments by electrophoresis and hybridisation to nucleic acid probes containing repetitive nucleotide sequences. The use of such mini- or micro-satellite probes tends to yield patterns specific to an individual rather than to a species, hence their value in forensic analysis but general unsuitability for meat speciation. In the present study, a cDNA probe based on conserved sequences contained in members of the actin multigene family has been evaluated for potential application in meat speciation. Genomic DNA was extracted from muscle and digested with BamHI before electrophoresis and hybridisation to a murine alpha-actin cDNA probe. Beef, pork, lamb, horse, chicken and fish DNA restriction fragments formed characteristic 'fingerprints' which were reproducible and varied sufficiently to allow discrimination even between closely-related species. However no major differences were seen between individuals of the same breed or between different breeds within a species. When DNA obtained from fresh tissue and also from meat heated at 120 degrees C was analysed, the gel patterns were essentially the same. An attractive feature of this approach is that it employs a single cross-reacting probe and set of conditions, and gives different patterns with all species so far studied. This simplicity suggests applications in meat speciation or related areas of biology. PMID- 22060814 TI - Effect of early post-mortem cooling on temperature, pH fall and meat quality in pigs. AB - The aim of this study was to investigate how early cooling of carcasses after slaughter by showering with cold water affected the rate of the pH fall post mortem, protein denaturation and drip loss. Eighty pigs were selected in pairs at debleeding according to sex and farm of origin. All pigs were halothane genotyped and glycolytic potential in LD analysed. One of each pair was cooled 30 min post mortem by showering with 10-12 degrees C water for 12 min. The control pig was treated normally except for the same delay before batch chilling commenced. The initial pH fall in LD and BF did not depend on the glycolytic potential in LD but at 5 to 6 and 24 hr post mortem pigs with the lowest glycolytic potential had the highest pH. Weight and lean meat content did not affect the cooling curve, i.e. the temperature fall. The results showed that it was possible to reduce the temperature in BF and LD by cooling at slaughter. The maximum difference in temperature between control and cooled carcasses 2hr post mortem was 2 and 1 degrees C in LD and BF respectively. The lowering of the muscle temperature early post mortem resulted in a reduced rate of the pH fall and a higher pH from 2 to 6 hr in the cooled carcasses. The rate of the pH fall in LD and BF seemed to be independent of temperature at levels above approximately 37 degrees C, but decreased linearly as the temperature dropped below approximately 37 degrees C. The cooling procedure used here did not result in a significant reduction in protein denaturation or drip loss, although there was a tendency towards lower drip loss in LD and BF in cooled carcasses. PMID- 22060815 TI - Sensory evaluation of young goat meat. AB - Loins from 12 young goats (three extensively reared-entire males, EE; three extensively reared-castrated males, EC; three intensively reared-entire males, IE; four intensively reared-castrated males, IC) were assessed by a trained panel of eight assessors for odour, flavour and texture using 100 mm unstructured scales. Procrustes analysis was used to produce the spatial configuration of the samples. The first principal axis explained 44.9% of the variation and was mainly based on textural attributes. The second principal axis accounted for 21.3% of the variation and was mainly related to odour and flavour. Samples obtained from groups EE and EC were more tender and juicy, whereas, IE animals produced a more cohesive meat. Groups IE and IC produced a more stringy meat, with a higher meaty odour and flavour. The rearing system affected texture more than odour and flavour, whereas sex had little effect on textural attributes compared with odour and flavour. PMID- 22060816 TI - Genomic diversity in switchgrass (Panicum virgatum): from the continental scale to a dune landscape. AB - Connecting broad-scale patterns of genetic variation and population structure to genetic diversity on a landscape is a key step towards understanding historical processes of migration and adaptation. New genomic approaches can be used to increase the resolution of phylogeographic studies while reducing locus sampling effects and circumventing ascertainment bias. Here, we use a novel approach based on high-throughput sequencing to characterize genetic diversity in complete chloroplast genomes and >10,000 nuclear loci in switchgrass, at continental and landscape scales. Switchgrass is a North American tallgrass species, which is widely used in conservation and perennial biomass production, and shows strong ecotypic adaptation and population structure across the continental range. We sequenced 40.9 billion base pairs from 24 individuals from across the species' range and 20 individuals from the Indiana Dunes. Analysis of plastome sequence revealed 203 variable SNP sites that define eight haplogroups, which are differentiated by 4-127 SNPs and confirmed by patterns of indel variation. These include three deeply divergent haplogroups, which correspond to the previously described lowland-upland ecotypic split and a novel upland haplogroup split that dates to the mid-Pleistocene. Most of the plastome haplogroup diversity present in the northern switchgrass range, including in the Indiana Dunes, originated in the mid- or upper Pleistocene prior to the most recent postglacial recolonization. Furthermore, a recently colonized landscape feature (approximately 150 ya) in the Indiana Dunes contains several deeply divergent upland haplogroups. Nuclear markers also support a deep lowland-upland split, followed by limited gene flow, and show extensive gene flow in the local population of the Indiana Dunes. PMID- 22060817 TI - Stereochemical dependence of 3JCH coupling constants in 2-substituted 4-t-butyl cyclohexanone and their alcohol derivatives. AB - Theoretical and experimental studies on (3)J(C2H6eq) NMR spin-spin coupling constants in both the 2-X-4-t-butyl-cyclohexanone (X = H, CH(3), F, Cl, and Br) and in their alcohol derivatives series are reported. Results thus found are rationalized in terms of the transmission of the Fermi contact contribution to such couplings. To this end, dependencies of (3)J(C2H6eq) couplings versus the C(2)-C(1)-C(6) angle are compared in both series for equatorial and axial X orientations. The main trend is described in terms of the rear lobes interaction. Besides, for X = halogen atom in equatorial orientation a rather strong interaction between oxygen and halogen lone pairs is observed, and its influence on (3)J(C2H6eq) couplings is discussed and rationalized in terms of different Fermi contact transmission pathways. PMID- 22060818 TI - The role of large-scale motions in catalysis by dihydrofolate reductase. AB - Dihydrofolate reductase has long been used as a model system to study the coupling of protein motions to enzymatic hydride transfer. By studying environmental effects on hydride transfer in dihydrofolate reductase (DHFR) from the cold-adapted bacterium Moritella profunda (MpDHFR) and comparing the flexibility of this enzyme to that of DHFR from Escherichia coli (EcDHFR), we demonstrate that factors that affect large-scale (i.e., long-range, but not necessarily large amplitude) protein motions have no effect on the kinetic isotope effect on hydride transfer or its temperature dependence, although the rates of the catalyzed reaction are affected. Hydrogen/deuterium exchange studies by NMR-spectroscopy show that MpDHFR is a more flexible enzyme than EcDHFR. NMR experiments with EcDHFR in the presence of cosolvents suggest differences in the conformational ensemble of the enzyme. The fact that enzymes from different environmental niches and with different flexibilities display the same behavior of the kinetic isotope effect on hydride transfer strongly suggests that, while protein motions are important to generate the reaction ready conformation, an optimal conformation with the correct electrostatics and geometry for the reaction to occur, they do not influence the nature of the chemical step itself; large-scale motions do not couple directly to hydride transfer proper in DHFR. PMID- 22060819 TI - Dechlorane plus in the atmosphere and precipitation near the Great Lakes. AB - Air (vapor and particle) and precipitation samples were collected at five sites (two urban, one rural, and two remote) on the shores of the Great Lakes from January 1, 2005 to December 31, 2009 as a part of the Integrated Atmospheric Deposition Network (IADN). The concentrations of the syn and anti isomers of Dechlorane Plus (DP), a highly chlorinated flame retardant, were measured in these samples. The highest concentrations of these compounds were generally observed at the rural site at Sturgeon Point, New York, which is located near DP's manufacturing facility in Niagara Falls, New York, and at the urban site at Cleveland, Ohio. A multiple linear regression model was applied to the concentrations of these compounds in the vapor phase, particle phase, precipitation, and for the three phases combined. This regression resulted in an overall (three phases combined) doubling time for the anti-DP isomer of 9.5 +/- 3.6 years, but for the syn- and total DP (syn + anti) concentrations, the overall regression was not statistically significant. These results suggest that there has been no significant change in the atmospheric concentrations of these compounds over the 2005-2009 time period. The effect of distance from the source in Niagara Falls was highly significant; for example, doubling the distance from Niagara Falls decreased the DP concentrations by about 30%. The effect of the number of people living and working within a 25-km radius of the sampling site (population density) was also highly significant but small; for example if this population doubled or halved, then the atmospheric DP concentrations would increase or decrease by only a few percent. PMID- 22060820 TI - Comparative dermal toxicity of dicyclohexylcarbodiimide and diisopropylcarbodiimide in rodents. AB - Dicyclohexylcarbodiimide (DCC) and Diisopropylcarbodiimide (DIC) are two representative chemicals in the carbodiimide class of chemicals used in industry as stabilizing agents. There is a potential of dermal exposure to these agents in chemical, pharmaceutical and recombinant DNA industries. The National Toxicology Program conducted a number of animal studies to characterize toxicity and carcinogenicity of DIC and DCC. Dermal administration of DCC and DIC in F344/N rats and B6C3F1 mice for 90-days induced skin irritation at the site of application in a dose-dependent manner. Microscopically, dose-dependent increases in epidermal hyperplasia and chronic inflammation were observed. We further evaluated the effects of dermal exposure of DCC and DIC in p53 haploinsufficient and Tg.AC mouse models. Results revealed the skin as the primary target of DCC and DIC exposure as indicated by dose - dependent skin lesions (hyperplasia, inflammation and necrosis). DCC induced squamous cell papillomas in Tg.AC mice but did not induce any neoplastic lesions in p53 haploinsufficient mice. Dermal application of DIC did not induce any neoplastic lesions in Tg.AC mice and p53 haploinsufficient mice. Based on these studies, it was predicted that DIC would be negative and DCC positive for carcinogenic activity in the traditional two year bioassay. In the subsequent studies, the carcinogenic potential of DIC only in F344 rats and B6C3F1 mice in a traditional 2-year chronic carcinogenicity bioassay was evaluated by the dermal route. Findings revealed the skin as the major target organ of toxicity in both sexes in rats and in male mice. There were no neoplastic lesions observed in rats or mice with the administration of DIC. In rats, there were clinical signs of toxicity in the highest dose-group which included ataxia, excitability, impaired gait, low muscle tone, abnormal breathing, lethargy, and seizures. This was accompanied by non-neoplastic lesions in the brain and lung only at the highest dose level. In conclusion, both DIC and DCC are dermal toxicants. DIC did not have any carcinogenic activity in transgenic mouse models or in the traditional NTP two-year carcinogenicity studies in F344 rats and B6C3F1 mice. DCC was positive in the Tg.AC mouse model and likely to be carcinogenic in the 2-year bioassay as well. PMID- 22060821 TI - Prospective evaluation of the interobserver reliability of the 4Ts score in patients with suspected heparin-induced thrombocytopenia. PMID- 22060822 TI - Description of two new gill myxozoans from smallmouth (Micropterus dolomieu) and largemouth (Micropterus salmoides) bass. AB - Two previously undescribed species of myxozoan parasites were observed in the gills of bass inhabiting the Potomac and James River basins. They are described using morphological characteristics and small-subunit (SSU) rDNA gene sequences. Both were taxonomically identified as new species of Myxobolus; Myxobolus branchiarum n. sp. was found exclusively in smallmouth bass, and Myxobolus micropterii n. sp. was found in largemouth and smallmouth bass. Small, spherical, white plasmodia of M. branchiarum from smallmouth bass were observed grossly in the gills; these plasmodia had an average length of 320.3 um and width of 246.1 um. The development of the plasmodia is intralamellar in the secondary lamellae of the gills. Mature spores were pyriform in shape with a length of 12.8 +/- 1.4 (8.1-15.1) um and width of 6.9 +/- 1.1 (4.0-9.0) um. Analysis of SSU rDNA identified M. branchiarum in a sister-group to 3 species of Henneguya , although morphologically caudal appendages were absent. Myxobolus micropterii observed in the gills of largemouth and smallmouth bass had larger, ovoid, cream-colored plasmodia with an average length of 568.1 um and width of 148.1 um. The cysts developed at the distal end of the gill filament within the primary lamellae. The mature spores were ovoid in shape with a length of 10.8 +/- 0.7 (9.2-12.2) um and width of 10.6 +/- 0.6 (9.0-11.8) um. SSU rDNA analysis placed M. micropterii in a sister group with Henneguya lobosa and Myxobolus oliveirai . The highest prevalence of M. branchiarum was observed in the gills of bass collected from the Cowpasture River (50.9%). Prevalence was 44.6% in bass from the Potomac River and only 4.3% in bass collected from the Shenandoah River. A seasonal study of M. branchiarum , which included both infected and uninfected smallmouth bass, determined that a significantly higher intensity was observed in the spring than in the summer (P < 0.001) or fall (P = 0.004). In an analysis excluding uninfected bass, a higher intensity was observed in the spring than in the summer (P = 0.001) or fall (P = 0.008). Prevalence and seasonal differences were not determined for M. micropterii . PMID- 22060823 TI - Incidence and risk factors of antiretroviral treatment failure in treatment-naive HIV-infected patients at Chiang Mai University Hospital, Thailand. AB - BACKGROUND: The use of combination antiretroviral therapy (cART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment especially in resource limited settings. In this study, we aimed to determine the incidence and risk factors of treatment failure in a cohort of treatment-naive Thai HIV-infected patients. METHODS: A retrospective cohort study was conducted among HIV-infected patients initiating their first cART at Chiang Mai University Hospital, Thailand. RESULTS: From January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean age was 37.9 +/- 8.6 years. The median baseline CD4 count was 57.7 cells/mm3 (IQR 22, 127). GPO-VIR(r) (a fixed-dose combination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients, 83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of virological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest predictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed immunological failure. A low CD4 cell count at baseline (< 100 cells/mm3) and the increment of CD4 cell count of < 50 cell/mm3 after 6 months of cART were the predictors for immunological failure (p < 0.001). CONCLUSIONS: This study demonstrated that even in resource-limited settings, the high rate of success could be expected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline CD4 cell count are the predictors for unfavorable outcome of cART. PMID- 22060824 TI - High-pressure effects on oxidation of nitrosylmyoglobin. AB - The rate of oxidation of nitrosylmyoglobin by oxygen decreases with increasing hydrostatic pressure. At 15 degrees C in air-saturated solution with ionic strength 0.16 and pH 6.8 (tris-buffer), the first-order rate constant is smaller by a factor of 5 at 300 MPa compared to ambient conditions. The pressure-effect on rate is not primarily caused by protein denaturation, as the presence of urea (up to 4 M) at ambient pressure increases the rate of oxidation. From rate/pressure data a volume of activation of +8 ml.mol(-1) and a compressibility coefficient of activation of -3 * 10(-8) ml.mol(-1) Pa(-1) is estimated. PMID- 22060825 TI - Post-mortem kinetics of meat tenderness and the components of the calpain system in bull skeletal muscle. AB - Eight strip loins (M. longissimus dorsi) from pasture fed Friesian bulls were aged at 15 degrees C for a range of times from 1 to 120 h. pH declined from 6.29 (SE 0.119) one hour post slaughter to an ultimate pH of 5.48 (SE 0.013). The activities of the components of the calpain system (MU-calpain, m-calpain and calpastatin) were determined after separation on a DEAE-sephacel column. There was a dramatic decline in MU-calpain activity post slaughter with a complete disappearance within 48 h. The rates of decline in m-calpain and calpastatin activity were slower with 30% and 50% remaining 120 h post slaughter, respectively. The rapid decline in MU-calpain activity relative to the calpastatin activity is likely to reduce the degree of tenderisation and ultimate tenderness of the meat. PMID- 22060826 TI - Lean colour of green and matured Parma hams: Comparative evaluation and technological relevance of sensory and objective data. AB - Research has been conducted on the relationship between sensory evaluation and objective measurement of pork colour. The study also investigated the relationship between the colour of fresh meat and the colour of matured hams. Sensory evaluation was carried out at 24 h post mortem on the freshly cut surfaces of green hams trimmed for Parma ham production. Objective measurements were performed at the same time on Semimembranosus and Biceps femoris muscles with a Minolta Chromameter Reflectance II CR200/08. Cold carcass weight, lean content, trimmed ham weight, 45 min and 24 h post mortem pH of Semimembranosus muscle were also recorded. The hams were processed according to Parma ham technology. Weight losses at standard processing times were collected. At the end of processing a sample of about one-third of the hams was evaluated for internal lean colour and lean firmness both by sensory panel and objective measurements. Proximate composition was also determined. The results showed highly significant relationships between colour sensory scores and the coordinates L (*), b (*) and hue of the C.I.E. L (*)a (*)b (*) colour system. Among the other parameters measured on fresh meat only 24 h pH was related at a very significant level with sensory and objective colour values. Correlation coefficients were generally higher for Semimembranosus than Biceps femoris. Matured ham colour was linked with fresh meat sensory judgements, L (*), hue and a (*) values. The relationship, though, was not sufficiently strong for use in predicting the colour of matured hams from green ham characteristics. Processing appears to have a positive effect on the colour of pale meat. Weight losses were mainly linked with lean meat content; other quality attributes being less important. Lean firmness of matured hams was related to the colour and pH of the fresh meat. PMID- 22060827 TI - Production of salami from ostrich meat with strains of Lactobacillus sake, Lactobacillus curvatus and Micrococcus sp. AB - The aim of this study was to produce Italian-type salami from ostrich meat using different combinations of Lactobacillus sake, Lactobacillus curvatus and Micrococcus sp., and to compare the sensory characteristics of these products to that of salami produced with glucono-delta-lactone (GdL). Meat inoculated with starter cultures was fermented for four days (20-22 degrees C, 97-99% RH) and ripened for a further 11 days (16-18 degrees C, 40-60% RH). Cell counts of lactic acid bacteria and micrococci, and changes in pH were determined daily during fermentation. According to texture and sensory evaluation, the best salami was produced by a starter culture containing L. curvatus DF 38 and Micrococcus sp. MC 50. PMID- 22060828 TI - Risk factors associated with bruising in red deer at a commercial slaughter plant. AB - Bruising of slaughter animals has both economic and welfare implications. In order to identify potential risk factors we surveyed bruising of red deer carcasses from a single Deer Slaughter Plant (DSP) over a three year period. Downgrading due to bruising did not vary between the three years surveyed [1991, n = 21 454, 6.5% downgraded (dg); 1992, n = 22 289, 7.9% dg; 1993, n = 22 262, 6.1% dg]. From an intensive examination of one year's kill (1991) we related the incidence of bruising to various preslaughter transport, seasonal and animal variables. Bruising varied significantly with time of year, hot carcass weight, distance transported, carrier company and carcass fatness. Bruising was related to duration of lairage for some periods of the year which varied with sex. The majority of bruising was on one or other hindquarter implying a consistent cause of the damage. Carcass quality and deer welfare can be best protected by careful driving, by only transporting animals in good condition and avoiding transporting males during the rut. PMID- 22060829 TI - Cassava as a non-conventional filler in comminuted meat products. AB - Cassava (Manihot esculenta) was used as an unconventional filler to produce affordable comminuted meat products that stored well under tropical conditions without refrigeration. The study involved two experiments. In experiment 1, five different emulsion-type pork sausages containing 5.4, 9.0 and 10.0% mould-free cassava flour, 5.4% crude full fat soy flour and a control without filler were assessed 0 and 7 days after preparation. A 40-member taste panel sensorily assessed the products in a 5 * 2 factorial (treatment * storage occasion) experiment based on the external appearance of the uncooked products and the external and internal colour, consistency, texture, aroma and taste of the cooked products. Although the panel judged products with 5.4% cassava flour as the best, the 9% inclusion level of cassava flour was found not to compromise the organoleptic qualities of the product. At this level 54 000 cedis (US$150) was saved on the cost of producing 1t of the product. In experiment 2, the sausages were pasteurised at 80 degrees C for 1 h and stored in a 4:1 vinegar-sugar solution or a 1:1:50 vinegar-sugar-water solution at 5 and 30 degrees C. Storage in 4:1 vinegar-sugar medium arrested bacterial growth over the 7-day monitoring period. It was concluded that 9% cassava flour could conveniently replace fat in comminuted meat products and a combination of pasteurisation and storage in vinegar-sugar solution is an effective method of storage of such products in the tropics. PMID- 22060830 TI - Cured colour development during sausage processing. AB - A study of colour evolution in dry cured sausage manufactured using industrial technology was made. Parameters which define changes related to nitrosation during curing were determined. The main changes in the colour characteristics of Spanish sausage took place during the fermentation stage. pH, nitrate and nitrite concentration, pigment nitrosation index, pigment discoloration index, a(*), b(*), C(*) and H(*) values decreased during this stage. However, the nitrosation of the myoglobin pigment continued during the whole curing process. The percent conversion of total pigments to the cured nitric oxide heme pigment form was about 70% in the minced mix, and it increased gradually to about 90% in the final product. During fermentation nitrites reacted with myoglobin (Mb) to form nitrosomyoglobin (NOMb) and metmyoglobin (MetMb), which reduced to NOMb during the drying process. PMID- 22060831 TI - Consumer assessment of the effect of electrical stimulation on the colour and colour stability of Semimembranosus muscles. AB - The influence of effective low voltage electrical stimulation on the colour stability of beef topside (semimembranosus) muscles, during storage and retail display was studied using objective measurements and subjective assessments. Earlier results obtained from objective measurements demonstrated that during a three day retail display period, stimulated topsides had a greater loss of colour than non-stimulated topsides, and primal cuts aged for 33 days at 0 degrees C before display suffered faster changes to colour during retail presentation than cuts aged for 5 days. To relate results obtained using objective methods to consumer perceptions of meat quality, consumer perceptions of samples of meat displayed for 3 days in the retail cabinets of a major local supermarket were recorded. A total of 960 consumers were asked to evaluate topside steaks for meat and fat colour, meat discolouration and acceptability. During 3 days of retail display, consumers did not perceive differences in the extent of discolouration of topside steaks from electrically stimulated and non-stimulated carcasses; for the majority of the treatment groups (high or low pH muscles, 5 or 33 day ageing, 1-3 day retail display) there were no significant differences, for any of the scored attributes, between stimulated and non-stimulated samples. However, for samples in the fresh (5 days ageing), high pH (5.8-6.0) treatments group, lean meat colour and acceptability for the stimulated samples were, on some of the days on display, given significantly (P < 0.05) better ratings by the consumers than those from corresponding non-stimulated samples. PMID- 22060833 TI - Improved oxidative stability of veal lipids and cholesterol through dietary vitamin E supplementation. AB - The influence of dietary vitamin E supplementation on the alpha-tocopherol content of muscle membranes and on the resultant oxidative stability of veal was investigated. Daily supplementation of veal calves with 500 mg vitamin E in the form of alpha-tocopherol acetate for 12 weeks after birth increased muscle and membranal alpha-tocopherol concentrations approximately 6-fold over those of control animals. Oxidative stability of mitochondrial and microsomal lipids was enhanced by dietary supplementation as indicated by the results of an oxidative assay using hydrogen peroxide-activated metmyoglobin as the catalyst of oxidation. Muscle lipid and cholesterol stability was also improved by supplementation. PMID- 22060834 TI - Effects of high-pressure treatment on the ultrastructure and thermal behaviour of beef intramuscular collagen. AB - Effects of high-pressure treatment on the ultrastructure and thermal behaviour of beef intramuscular collagen were investigated to clarify the pressure effects on background toughness attributed to the presence of connective tissue in the muscle. No significant differences in the ultrastructure, electrophoretic pattern, thermal solubility and thermogram of differential scanning calorimetric analysis of the intramuscular collagen were observed among the control (untreated) and pressurized muscles. From the results, it is suggested that the pressurization has no significant effects on the connective tissue and the pressure-induced tenderization of meat could probably be caused only by the improvement of actomyosin toughness attributed to the myofibrillar proteins. PMID- 22060835 TI - The concentrations of free magnesium and free calcium ions both increase in skeletal muscle fibres entering Rigor mortis. AB - Metabolic inhibitors have been used to induce rigor in mammalian muscle fibres previously injected with the Ca(2+)- and Mg(2+)-binding dye arsenazo III. The spectral changes which ensue, after the onset of rigor, indicate that a large increase in intracellular free Ca(2+) occurs (to more than 10(-4)m) but that this is preceded and accompanied by a substantial increase in free Mg(2+) concentration (to 2 mm or more) presumably as a result of the decline in the ATP concentration within the cell. Fibres in rigor have been treated with the divalent cation ionophore A23187 to enable Ca(2+) and Mg(2+) to be extracted selectively from the cell by extracelluar chelating agents. Optical measurements performed during this extraction, confirm that both Ca(2+)- and Mg(2+)-binding to arsenazo III contribute to the absorption change which is recorded, whilst the treatment of relaxed fibres with the ionophore together with EDTA, produces an absorption change which, in combination with other measurements, indicates that in the sarcoplasm of the resting relaxed cell, approximately one third of the dye is complexed with Mg(2+). This indicates that the cytoplasmic free Mg(2+) concentration, prior to rigor onset, is about 0.5 mm. PMID- 22060836 TI - Effects of meat quality and storage on the breakdown of adenosine triphosphate in muscle from swine. AB - The quality of pork is dependent on animal genotype, pre-slaughter handling, processing, maturation, and storage. We investigated the pattern of adenosine triphosphate (ATP) breakdown as it related to these factors. Samples of the thoracis portion of the longissimus dorsi muscle were obtained from 19 randomly selected German Landrace-Pietrain crossbreed swine. Based on their 40 min post mortem pH and electrical conductances, three groups were classified: (1) PSE meat, pH <= 5.6 and conductance >10 mS (n = 7); (2) intermediate quality, pH 5.6 6.0 and conductance between 4 and 10 mS (n = 5); and (3) normal quality, pH >= 6.0 and conductance < mS (n = 7). Hence, the animals investigated included those susceptible to malignant hyperthermia (porcine stress-syndrome). Twenty-four hours post mortem samples were evaluated for the following parameters: ATP metabolism, pH values, electrical conductance, meat colour, water binding capacity, shear force and general composition (i.e. total protein, fat, mineral and water contents). Muscle composition was the same in each group, but for the other parameters there were clear differences. Following different storage periods and conditions (1 or 5 days at 4 degrees C and 27 days at -18 degrees C), the degree of ATP metabolism as well as general meat quality (i.e. including sensory evaluation) were reassessed. Samples from the pre-selected groups became less discernible following prolonged storage. In all animals, the pattern of ATP breakdown was similar, the major metabolites including inosine monophosphate, hypoxanthine, adenosine monophosphate, and inosine. The degree of breakdown was dependent on the duration and temperature of storage, but not on animal type. The muscular samples for the intermediate and normal muscle groups, which were stored for 27 days at -18 degrees C, were given the highest sensory evaluation scores. The simple HPLC measurement of ATP metabolism was considered as a useful means to assess appropriate storage. PMID- 22060837 TI - The effect of growth rate and ultimate pH on meat quality of lambs. AB - Entire male Romney lambs (n = 60) were grown slowly (67 g/day) and slaughtered at 14 months of age at an anticipated carcass weight of 18 kg. Another group of ram lambs (n = 15) from the same genetic background (born 7 months later) were grown rapidly (162 g/day) for 7 months and slaughtered at the same time and at a similar carcass weight. Preslaughter shearing (20 days prior to slaughter) and swim washing (3 times) were variously imposed upon the 14-month old lambs to give them a graded preslaughter stress. The lambs were head-only electrically stunned and slaughtered. Dressed carcasses were electrically stimulated at 20 min post mortem for 90 s at 14.3 pulses/s, 1.8-2 A and 1130 V peak, then held at 12 degrees C for 2 h and frozen so that the deep leg reached -4 degrees C in 12 h. The ultimate pH was measured for the longissimus dorsi, and loin samples were assessed by tenderometer and a sensory panel. The groups with the greatest stresses imposed had the highest ultimate pH. The most tender meat came either from carcasses with an ultimate high pH greater than 6.3 or from young lambs with an ultimate pH from 5.5-5.7. While 7-month old lambs were slightly more tender than the 14-month old lambs of iso pH, the 14-month old lambs of high pH were the most tender. This suggests that age-related connective tissue effects were minimal for the loin. The shear force values and taste panel tenderness scores were linearly related. When the shear force and panellists' tenderness scores were expressed in relation to ultimate pH, there was a decreased acceptance of meat with a moderate ultimate pH between 5.8 and 6.0. Panel texture assessments showed a less clearly defined, but statistically significant decrease in acceptance at pH 5.8-6.0. Other sensory attributes of flavour, juiciness and aroma were uniform across the whole ultimate pH spectrum. PMID- 22060838 TI - Effect of feed protein on carcass composition and meat quality in steers. AB - Forty-five Charolais steers were fed one of four experimental regimes containing maize silage and maize grain supplemented with either protected soyabean-rapessed meal or linseed meal. The first three regimes were formulated to supply the same energy and different protein levels with soyabean-rapessed meal: low (L-SRM), medium (M-SRM) and high (H-SRM). The fourth regime consisted in feeding the same amount (kg/day) of linseed meal as that of soyabean-rapessed meal in the H-SRM regime (LSM). As the protein level increased from L-SRM to H-SRM, the daily weight gain of steers increased and the carcass composition was changed towards higher muscle and lower fat proportions. Though the actual supply of feed protein by regime LSM was close to that achieved with M-SRM, the effect of linseed meal supplementation on weight gain and carcass composition was comparable to that obtained by feeding the high protein level (H-SRM). The dry matter content increased and the heme pigments and lipids contents decreased in longissimus thoracis muscle as the protein supply increased from the low to the high level. Again the amplitude of the differences in meat quality with L-SRM were similar in H-SRM and LSM. Muscle colour, connective tissue and mechanical strength remained practically unaffected by the protein treatments. However, meat was scored less tender in H-SRM and less juicy in treatment LSM than in treatment L-SRM. The results obtained with linseed meal suggest a specific effect of type of feed protein on beef carcass composition and meat quality. PMID- 22060839 TI - Effects of various cellulose gums on the quality parameters of low-fat breakfast sausages. AB - Composition, textural, viscoelastic, hydration, colour and sensory attributes of regular (26% fat) and low-fat (13%) pork breakfast sausages with and without cellulose gums (two types of carboxymethyl cellulose (CMC-I and -II) and microcrystalline cellulose (MCC-I and -II)) were investigated. The fat was replaced with water in low-fat products. In cooked low-fat sausages, the fat content decreased by 52-60%, and moisture content reduced by 61-65% of the initial values. The cooked high-fat products' composition showed an increase of about 6% fat and a decrease of 7% moisture due to cooking. MCC was more effective in retaining moisture compared to CMC. Product lightness was reduced due to both CMC and MCC. Gums have not affected fat content, water holding capacity, redness, yellowness, hardness, chewiness and gumminess. High-fat products were less elastic and easier to chew. Springiness was reduced by CMC-II and cohesiveness by other cellulose gums. PMID- 22060840 TI - The effects of breed and halothane sensitivity on pig meat quality. AB - The effects of halothane sensitivity and breed (Belgian Landrace BL and Landrace L), and their interactions on carcass and meat quality were analysed. Also the effect of breed (Pietrain P, BL, L, Large White LW and Duroc D) on carcass and meat quality was studied in a sample of 153 gilts. Each of the half-carcasses was cut and fully dissected to obtain lean percentage. The following measurements of meat quality were carried out: muscle pH, electrical conductivity (QM) and light scattering (POP). Muscle reflectance (GOFO value), muscle protein solubility (MPS) and intramuscular fat content were also determined. The results obtained in this study revealed the effect of halothane gene on all of the traits studied. The halothane-positive animals showed less fat thickness and more lean percentage in the carcass. The P and BL breeds had more lean percentage in the carcass and a better lean-to-bone ratio compared with L, LW and D. The L breed was intermediate. Stress sensitivity is an important factor affecting the inverse relationship between carcass quality and meat quality. Those breeds free of the halothane gene (LW and D) had the best meat quality. The L breed was in an intermediate position, but more similar to halothane-negative breeds. The Duroc breed had significantly higher intra-muscular fat (>2.0%), required for optimum fresh meat quality and for the production of Spanish dry-cured ham of high quality. PMID- 22060841 TI - The influence of high temperature, type of muscle and electrical stimulation on the course of rigor, ageing and tenderness of beef muscles. AB - The course of rigor mortis (rigor), ageing and tenderness has been evaluated for three beef muscles; M. biceps femoris (BF), M. semimembranosus (SM) and M. semitendinosus (ST), when entering rigor at constant temperatures of 15 and 37 degrees C respectively, with and without electrical stimulation (ES/NS) (85 V, 14 Hz and 32 s). The course of post-mortem changes has been registered by isometric tension, by shortening of unrestrained muscle strips and by following the pH decline and the changes in metabolites, such as ATP and CP. Ageing at +4 degrees C was recorded by measuring Warner-Bratzler (W-B) shear values 2, 8 and 15 days post mortem. On the last occasion, the sensory properties of the cooked meat were also evaluated. Maximum shortening and isometric tension were higher at 37 degrees C as compared to 15 degrees C, whereas ES did not reduce rigor shortening. A high correlation between maximum shortening and the ATP-level at the onset of the shortening rapid phase was found (r = 0.77(***)), which could explain the greater shortening obtained at 37 degrees C compared to 15 degrees C. Rigor shortening is an important phenomenon governing meat tenderness as tenderness is highly affected by rigor temperature but not by ES. This was the case for muscles SM and ST but not for BF muscle. Even though tenderness was measured after ageing (15 days post mortem), shortening during rigor seems to be more important for toughness when rigor mortis occurs at 37 degrees C than any suggested tenderizing effect due to increased proteolysis in this temperature region. PMID- 22060842 TI - Detection of micrometastatic cells in peripheral blood and bone marrow fluid of stage I-III Japanese breast cancer patients and transition following anti-cancer drug treatment. PMID- 22060844 TI - Evaluation of rib steak colour from Friesian, Hereford and Charolais heifers pastured or overwintered prior to slaughter. AB - Heifers (n=10) were randomly selected from the slaughter line of a local factory each month for a period of 21 months. Rib steak (sampled at the 10th rib) from the left side of each carcass was taken for analysis. The cattle breeds selected during this study were Friesian, Hereford and Charolais. The mean weight of the left side for all carcasses was 146.6 (S.E.M.= 1.0kg). Graded carcasses selected for sampling during this trial were classified using the EUROP scale and the specific heifer grades chosen were factory grades EO4L and EO4H. Initial Hunter 'a' values (on the day of arrival in the laboratory) of rib steak from heifers finished between November and March (overwintered) were significantly (P<0.001) higher than Hunter 'a' values from heifers finished between April and October (pastured). After storage at 4 degrees C under simulated retail display conditions for 6 days, the Hunter 'a' values for overwintered samples were also significantly (P<0.001) greater than those for pastured samples. Breed also had an effect on the colour of the meat. After storage for 6 days, Hunter 'a' values of rib steak from Charolais were significantly (P<0.05) higher than either Friesian or Hereford. Pastured heifers had significantly (P<0.05) higher levels of the monounsaturated fatty acid C16.1 in the total lipid fraction of rib steak (neutral and polar) than samples taken from overwintered heifers. Pastured heifers had significantly (P<0.01) higher levels of the polyunsaturated fatty acid (PUFA) C18.3 in the phospholipid fraction than those from overwintered cattle. However, Hereford had significantly (P<0.05) higher levels of C14.0, C16.1 and C18.0 in the phospholipid fraction than those found in Friesian and Charolais. The level of alpha-tocopherol in the muscle was not affected by either pasturing/overwintering or breed. However, Continental breeds had significantly (P<0.05) higher levels of alpha-tocopherol in adipose tissue than Friesian. PMID- 22060843 TI - Pandemic A/H1N1v influenza 2009 in hospitalized children: a multicenter Belgian survey. AB - BACKGROUND: During the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium. METHODS: From July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR) and probable (positive influenza A antigen or culture) pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers. RESULTS: During the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had >= 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%), concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002) and a higher mortality rate (4% vs 0%, p = 0.06). Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications. CONCLUSION: Although influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar. PMID- 22060845 TI - In vitro (31)P NMR studies on biopsy skeletal muscle samples compared with meat quality of normal and heterozygous malignant hyperthermia pigs. AB - Phosphorus nuclear magnetic resonance ((31)P NMR) measurements were made to determine muscle energetic metabolism on muscle biopsy samples of heterozygote malignant hyperthermia (Nn) and normal (NN) pigs DNA tested on occurrence of mutation in RYR 1 gene. Biopsy samples (approx. 1 g) were obtained by spring loaded biopsy instrument (Biotech, Slovakia) from Longissimus dorsi (LD) muscle at 80 kg live weight. The spectra were recorded at 121 MHz on a VXR 300 (Varian) spectrometer in 10 mm diameter tube (maintained at 39 degrees C) for 50 min. pH of bioptates after NMR measurements were also measured at 60 min. The changes in inorganic phosphate (Pi), phosophocreatine (PCr) and adenosine triphosphate (ATP) were faster in heterozygote malignant hyperthermia (MH; 29 crossbred White Meaty*Pietrain) than in normal (13 Duroc, Yorkshire and White Meaty). The values of PCr at 20 min and pH at 60 min after taking biopsy allowed discrimination between NN and Nn pigs and significant (P<0.05) differences were also found between two subgroups in heterozygote MH pigs with different rate of post mortem muscle metabolism. The values of PCr and pH as measured at definite time on the biopsies, were significantly (P<0.05) correlated with the rate of post mortem metabolism (pH) and with meat quality traits (r approx. 0.4-0.6). The (31)P NMR measurements pointed to impaired muscle energetic metabolism connected with the occurrence of mutation on the RYR 1 gene in heterozygote MH pigs. PMID- 22060846 TI - Proximate composition, selected minerals, cholesterol content and lipid oxidation of mechanically and hand-deboned chickens from the Jordanian market. AB - Samples of chicken were prepared using four treatments: (1) manual deboning of whole chickens; (2) manual deboning of skinned chickens; (3) mechanical deboning of whole chickens; (4) mechanical deboning of skinned chickens. The meat was packaged in polyethylene bags, frozen and stored at -18 degrees C. Treatments 2 and 4 resulted in the lowest fat content. Some minerals, e.g. Fe, Na, Al, K, and Mg did not vary among the four products, while others, e.g. Ca, Zn and Mn were significantly higher in Treatments 3 and 4 compared with Treatments 1 and 2. Cholesterol content was directly proportional to fat content; Treatment 3 gave the highest cholesterol content, while the lowest cholesterol level resulted from Treatment 2. Thiobarbituric acid (TBA) determinations to evaluate oxidative rancidity of fat in the samples showed that Treatments 1 and 3 gave significantly higher values than Treatments 2 and 4. PMID- 22060847 TI - The effect of pig genetics on palatability, color and physical characteristics of fresh pork loin chops. AB - The objective of this study was to characterize the quality attributes of pork derived from pigs of the following backgrounds: Duroc, Pietrain (Halothane negative, NN), Pietrain (Halothane positive, nn), Berkshire, Hampshire (rn+), Hampshire (RN-), and a synthetic line. A 10-member panel was trained to evaluate visual appearance of uncooked lean and fat, and flavor and texture of cooked chops. Hunter L*, a*, and b* values, hue angle, cookloss and Warner-Bratzler shear force were also determined. Visual color differences occurred due to genetic background. Chops from Duroc, Berkshire, Pietrain-nn, and the synthetic line were least pink. Chops from Berkshire carcasses appeared to have the most marbling in the lean and those from Pietrain-nn pigs appeared to have the least. Chops from Pietrain-nn and Hampshire-rn+ carcasses had the highest a* values while chops from Duroc, Pietrain-NN, and Hampshire-RN- carcasses had the lowest. Cook loss from chops from Duroc carcasses was lower than that from Hampshire rn+, Pietrain-NN and synthetic line carcasses. Shear force was highest for chops from Pietrain-nn and Hampshire-rn+ carcasses. Chops from Hampshire-RN- carcasses were most juicy followed by those from Hampshire-rn+, Pietrain-NN, Berkshire and Duroc carcasses. Shear force was positively correlated with abnormal flavor intensity, metallic taste, and chewiness (r=0.72, 0.94, and 0.69, respectively), and negatively correlated with sweetness (r=-0.73). Overall, genetic background had significant effects on many of the quality characteristics evaluated. PMID- 22060848 TI - Volatile profiles, lipid oxidation and sensory characteristics of irradiated meat from different animal species. AB - Irradiated meats produced more volatiles and higher 2-thiobarbituric acid reactive substances (TBARS) than nonirradiated regardless of animal species. Irradiation not only produced many new volatiles not found in nonirradiated meats but also increased the amounts of some volatiles found in nonirradiated meats. The amounts of volatiles in aerobically packaged irradiated meats decreased with storage while those of nonirradiated meats increased. TBARS values were the highest in beef loin, followed by turkey breast and pork loin regardless of irradiation, packaging, and storage time. TBARS of meats showed positive correlation with total volatiles, but preference scores between irradiated and nonirradiated were similar. PMID- 22060849 TI - A national audit of retail lamb loin quality in Australia. AB - A retail audit of lamb loin tenderness was conducted over a 12-month period to determine the variation in tenderness of Australian lamb. Tenderness was objectively measured using Warner-Bratzler (WB) shear force. Muscle pH and cooking loss were determined on all samples and colour was measured on a sub sample of loins. A total of 909 midloins from retail butcher shops and supermarkets located in four Australian capital cities (Sydney, Canberra, Melbourne, and Perth) were evaluated at four sampling times (December 1997 and March, June, and October 1998). Overall, 20.3% of all midloins purchased had a WB shear force value above the threshold level of 5 kg. Generic samples from Melbourne butcher shops were similar for WB shear force on average to the generic samples from Canberra and Sydney, whereas those from Melbourne supermarkets had significantly (P<0.001) higher WB shear force and were in line with generic samples from Perth. In both Canberra and Perth, alliance (branded) lamb had a greater WB shear force (P<0.05) than generic lamb. No relationship was found between price per kg and shear force (r=0.02) for loins purchased in Sydney (n=220). Price per kg differed between months (P<0.001) and suburbs (P<0.001), but not between retail butcher shops and supermarkets. Of the midloins tested, 10.3% had a pH above the critical point of 5.8. Midloins from the December 1997 sampling had a lower pH (P<0.01) than those sampled at other months. Those sampled in Melbourne and Perth had a similar mean pH, which were lower (P<0.001) than Canberra and Sydney samples. The findings from this quality audit suggest that there is room to improve the tenderness of Australian lamb sold in the domestic market. A lamb eating quality assurance system, based on set protocols, is one approach that is currently being investigated in Australia to ensure the supply of consistently high eating quality lamb to consumers. PMID- 22060850 TI - Use of Staphylococcus xylosus as a starter culture in dried sausages: effect on the biogenic amine content. AB - The main objective of this work was to investigate if the use of Staphylococcus xylosus S81 as a starter culture in sausage production can influence the amount of histamine during ripening, and the concentration of the other most important biogenic amines, by influencing the activity of the microbial amino oxidases as well as the aminoacid decarboxylases. The results confirm that the biogenic amines presence in foods is the consequence of a complex equilibrium between the composition of the medium and the enzymatic activities of the microbial population. In addition, the results suggest that the presence and relative activity of amino oxidases should be considered as an important characteristic in the selection of starter cultures used in the production of fermented foods. PMID- 22060851 TI - Use of oxygen sensors to non-destructively measure the oxygen content in modified atmosphere and vacuum packed beef: impact of oxygen content on lipid oxidation. AB - The ability of optical oxygen sensors to monitor the levels of oxygen in raw and cooked beef was investigated. Raw and cooked beef slices were vacuum packaged and cooked beef slices were modified atmosphere packaged MAP, (60% N(2): 40% CO(2)) and held under refrigerated display (4 degrees C) for 15 or 35 days for MAP and vacuum packed samples, respectively. Oxygen sensors attached to the inside of the lidding material in modified atmosphere packages, or inserted into vacuum packages, were capable of monitoring changes in oxygen levels in all packaged samples. Lipid oxidation of samples was measured at regular intervals. Oxygen contents detected, ranged from 1.15 to 1.26% and 0.07-0.55% in MAP and vacuum packed samples, respectively. Samples containing greatest levels of oxygen were most oxidised and cooked samples were significantly (P<0.05) more oxidised than raw samples. PMID- 22060852 TI - Identification of the goose species (Anser anser) in Italian "Mortara" salami by DNA sequencing and a Polymerase Chain Reaction with an original primer pair. AB - "Mortara" goose salami is a typical product of the Lomellina zone (Italy) and is home-made in accordance with old traditions. A Polymerase Chain Reaction (PCR) was set up using Italian goose breeds meat and the earlier mentioned product. A zone of the cytochrome b of mitochondrial DNA of goose was sequenced and a specific primer pair was successfully designed to identify the species Anser anser in salami. PMID- 22060853 TI - Electromagnetic scanning to estimate carcass lean content of Taiwan native broilers. AB - To estimate lean content of Taiwan native broiler carcasses accurately, objectively and rapidly, electrical conductivity measurements of broiler carcasses and other relative factors (carcass weight, length and temperature) were used in multiple linear regression analysis for lean prediction. Forty native broiler carcasses, with average market weight 2477.5+/-465.5 g, were scanned through a 10 MHz electromagnetic field created by an electromagnetic scanner (SA-3203) to measure the total body electrical conductivity (TOBEC) index. After scanning, each broiler carcass was separated into wing, breast, leg and back. Each primal cut was dissected into lean, fat and bone. The weight, length, temperature and TOBEC index of broiler carcass were significantly correlated with lean weight of broiler carcass (P<0.001). Regression analysis for lean estimation with carcass weight, length, temperature and TOBEC index showed higher coefficient of determination (R(2)=0.968) and lower coefficient of variation (CV=4.178) with an equation using beheaded carcass weight, temperature and TOBEC index as variables. PMID- 22060854 TI - alpha- and gamma-tocopherol levels in Nelore steer blood plasma after a single oral treatment of soybean oil deodorizer distillate (SODD). AB - The paper presents a study on the effect of a treatment of steers with a single oral dose of soybean oil deodorizer distillate (SODD) on the alpha- and gamma tocopherol blood plasma concentrations. SODD containing 1.95% of alpha-tocopherol and 8.45% of gamma-tocopherol in doses of 0.75, 1.50 or 2.25g/kg live weight was used on nine 2-year-old Nelore (Bos indicus) steers to promote increases in the plasma concentration of vitamin E. Tocopherol analyses were performed by HPLC on a C18 column, using a UV detector. The results showed that a single oral treatment of steers with SODD produces significant increases in plasma alpha- and gamma-tocopherol levels. The vitamin E content was increased up to four times the initial content, showing the high capacity of SODD as a source of vitamin E for bovines in a single oral dose with the objective of increasing vitamin E blood plasma concentrations and, consequently, the levels in the tissues, as well. PMID- 22060855 TI - The effects of ozone, chlorine dioxide, cetylpyridinium chloride and trisodium phosphate as multiple antimicrobial interventions on microbiological, instrumental color, and sensory color and odor characteristics of ground beef. AB - The impact of multiple antimicrobial interventions on ground beef microbial, color and sensory characteristics was studied. For this, beef trimmings were inoculated with Escherichia coli (EC) and Salmonella typhimurium (ST) then treated with either (1) 1% ozonated water followed by 5% acetic acid (OA), (2) 1% ozonated water followed by 0.5% cetylpyridinium chloride (OC), (3) 200 ppm chlorine dioxide followed by 10% trisodium phosphate (CT) or (4) control (C). Trimmings were ground, packaged and sampled at 0, 1, 2, 3 and 7 days of display for EC, ST, coliforms (CO), aerobic plate count (APC), instrumental color and sensory color and odor characteristics. The OA and OC treatments reduced (P<0.05) all bacterial types evaluated, while CT reduced (P<0.05) EC, CO and APC. The CT treatment was redder (P<0.05) in overall color than C, and there was no difference (P>0.05) in beef odor or off odor between OC, CT or C treatments. PMID- 22060856 TI - Reduction of microorganisms in ground beef using multiple intervention technology. AB - The effectiveness of multiple antimicrobial interventions on ground beef microbial, instrumental color and sensory characteristics through display was studied. Beef trimmings were inoculated with Escherichia coli (EC) and Salmonella typhimurium (ST) then treated with either: (1) 5% acetic acid followed by 0.5% cetylpyridinium chloride (AC); (2) 200 ppm chlorine dioxide followed by 0.5% cetylpyridinium chloride (CC); (3) 0.5% cetylpyridinium chloride followed by 10% trisodium phosphate (CT); or (4) control (C). Trimmings were ground, packaged and sampled through display for EC, ST, coliforms (CO), aerobic plate count (APC), and sensory color and odor characteristics. All treatments reduced (P<0.05) all bacterial types monitored through display. Ground beef from the CC treatment was similar (P>0.05) in redness (a*) to C. The CT treatment remained (P<0.05) redder (a*) in color, contained more (P<0.05) oxymyoglobin and had less (P<0.05) overall, worst point and percentage discoloration than C by day 7 of display. PMID- 22060857 TI - Effect of temperature on the radiation resistance of virulent Yersinia enterocolitica. AB - Yersinia enterocolitica, a food-borne pathogen, can be eliminated from meat using ionizing radiation. Commercial facilities may irradiate meat at refrigeration or frozen temperature, or packed in dry ice if the facility does not have refrigeration capabilities. The effect of temperature on the radiation resistance of Y. enterocolitica that contained the 70 kb large virulence plasmid was determined. A mixture of four Y. enterocolitica strains was inoculated into ground pork, which was then vacuum-packed, equilibrated to refrigeration or sub freezing temperatures, and irradiated to doses of 0.2, 0.4, 0.6, 0.8, and 1.0 kGy. The D(10) value, the radiation dose required to reduce the number of viable Y. enterocolitica by 90%, increased as product temperature decreased with values of 0.19, 0.19, 0.21, 0.40, 0.40. 0.38, and 0.55 kGy being obtained at +5, 0, -5, 10. -15, -20 and -76 degrees C, respectively. Meat product temperature should be considered when selecting a radiation dose required for elimination of Y. enterocolitica. PMID- 22060858 TI - Relationships between beef carcass shape and muscle to bone ratio. AB - Relationships between muscularity and muscle to bone ratio were investigated for beef carcasses of several breeds and crosses, and three genders using data from Bristol and Alberta. Side dissection data in terms of muscle, fat and bone weights were used to calculate muscle to bone ratios (MtoB) and muscularity indexes (MUSC) for the whole side or for the region around the femur bone. Highly significant breed and gender effects on MtoB and MUSC were shown for both the Bristol and the Alberta data sets, but the group differences for MtoB were not the same as those for MUSC despite the fact that these two characteristics were closely correlated. For both sets of data, for example, MUSC values at a common muscle plus bone weight were significantly higher for carcasses of bulls than heifers, but similarly adjusted MtoB values were generally higher for carcasses of heifers than bulls. Differences among breed groups were mainly in a similar direction for MUSC and MtoB, but the size of the differences varied widely. For example, relative to the Friesian, the Jersey breed had a significantly higher MtoB but a significantly lower MUSC, and carcasses of double-muscled bulls had a femur-region MtoB that was 19.2% greater than that of a group of Shorthorn-cross carcasses, but a MUSC that was only 1.7% higher. These findings show that because of the inconsistent relationships between muscularity and muscle to bone ratio among different classes of beef carcasses, lean meat yield cannot always be predicted without bias if measures of carcass shape are used as indicators of muscle to bone ratio. PMID- 22060859 TI - Bioassay for nisin in sausage; a shelf life study of nisin in cooked sausage. AB - A bioassay for nisin, an antimicrobial peptide used as a food additive, was developed for sausages based on nisin induced GFP-fluorescence (green fluorescent protein), and that could be performed on a microplate. The amount of GFP fluorescence was easily measurable and dependent on nisin concentration. This GFP bioassay for nisin had a detection limit in sausage as low as 0.9 ppm (0.9 MUg/g), and it was used to assay shelf life of nisin in cooked sausage. Of the added nisin 68% could be detected from the sausages after storage of 28 days at 6 degrees C. PMID- 22060860 TI - The effects of aging on moisture-enhanced pork loins. AB - The effects of preinjection aging time on pork loins injected with a salt/phosphate/lactate solution were investigated. Ninety-six fresh pork loins, in two replicates, were divided into two treatments. Loins in the first treatment were injected to 13% of loin weight at 1 day post-slaughter with a brine containing 2.17% salt/3.04% phosphate/20.8% lactate. The second group was injected with the same brine 4 days after slaughter. Color and Warner-Bratzler shear (WBS) force were measured immediately, 7 and 14 days after injection. Purge was measured 8 and 15 days postmortem. Western blots to measure troponin-T degradation were performed on samples from the two loins that resulted in the lowest shear force, and from the two loins that resulted in the highest shear force, as measured by Warner-Bratzler shear. The two loins with the most purge loss and the two loins with the least purge loss were also analyzed by Western blots for desmin degradation. The L(*) and b(*) color values were higher (P<0.05) and purge was greater (P<0.05) for loins injected 1 day postmortem than for loins injected 4 days postmortem. Western blots demonstrated that injection did not affect protein degradation. Therefore, differences between individual animals that affect protein degradation remain important regardless of injection treatment. PMID- 22060861 TI - Antioxidant, lipolytic and proteolytic enzyme activities in pork meat from different genotypes. AB - Oxidative processes in meat lead to meat quality deterioration. Meat has endogenous antioxidants and prooxidants, but information on factors influencing the activity of antioxidant enzymes in meat is limited. Lipolytic and proteolytic enzymes are involved in important aspects of meat quality. Our objective was to find differences between five different genotypes on the activity of antioxidant, lipolytic and proteolytic enzymes in meat. Forty Psoas major muscles of females of five different pig genotypes were used, Pietrain, Landrace, Large-White, lberian, and lberian*Duroc. Pre slaughter conditions were similar for all the genotypes. After slaughter, muscles were vacuum packed and frozen at -20 degrees C until required. Differences between genotypes were found for the activity of catalase and SOD, while GSH-Px showed no differences. The highest differences between breeds were found for the lberian breed where catalase had the highest activity. Catalase activity also showed differences between the white pigs, with large values for LR and lower activities in P. There were no differences in neutral lipase activities between the different genotypes while acid lipase and phospholipase showed significant differences. The activities of cathepsin B and H were significantly lower for Iberian pigs compared with other breeds except LR, while the ratio of cathepsin B+L/cathepsin B was higher in Iberian. The differences between genotypes found in enzyme activities suggest some genetic effects on the antioxidant, lipolytic and proteolitytic activity of pork meat. PMID- 22060862 TI - Effect of grass or concentrate feeding systems and rate of growth on triglyceride and phospholipid and their fatty acids in the M. longissimus thoracis of lambs. AB - Thirty-two male Ile-de-France lambs were used in a factorial 2*2 design to analyse the effects of feeding systems (grass outdoor, G, or concentrate and hay indoor: stall, S) and of growth rate (low, L, or high, H) on total lipids, triglyceride (TG) and phospholipid (PL) contents and their fatty acid composition in the longissimus thoracis muscle (L.T.). Contents were lower for TG (10.4 vs. 15.8 mg/100 g fresh tissue, P<0.05) and higher for PL (6.4 vs. 5.8 mg/100 g fresh tissue, P <0.05) in grass-fed lambs compared to stall-fed ones. TG of grass fed lambs displayed lower proportions of palmitic acid (C16:0), monounsaturated fatty acids (MUFAs), linoleic acid (C18:2n-6) and other (n-6) polyunsaturated fatty acids (PUFA) and higher proportions of stearic acid (C18:0), linolenic acid (C18:3n-3), cis 9, 11 trans C18:2 and trans monounsaturated fatty acids. In PL of the same lambs only lower MUFA, C18:2n-6 and (n-6) PUFA and higher C18:3n-3, (n 3) PUFA and cis 9, 11 trans C18:2 were observed. Growth rate had no effect on lipid, TG or PL contents of longissimus thoracis. However C18:0 proportions were higher in TG and lower in PL for low growth rate lambs. Low growth rate lambs had also lower cis 9, 11 trans C18:2 in TG. Thus, irrespective of growth rate, the muscle lipids characteristic of grass fed lambs fulfilled the recommended features of human food components much better than that of stall fed lambs, namely for CLA and C18:3n-3. The lower ratios of (n-6) to (n-3) PUFA displayed in grass fed lambs both in TG and in PL were also useful to discriminate all the grass fed lambs from all the stall fed animals. PMID- 22060863 TI - Determination of total fat and moisture content in meat using low field NMR. AB - The use of low field Nuclear Magnetic Resonance (LF-NMR) is shown to be a fast and accurate alternative to the use of drying and solvent extraction, to determine the content of raw or total fat and moisture in a biological system. The proposed NMR method for fat determination in minced meat proves to be a robust method that does not require sophisticated post handling of the experimental data. The calibration procedure is very easy, as a calibration value from a sample of known weight containing 100% oil is the only calibration needed for the proposed experimental set-up. On three sets, each containing 42 samples of minced beef where the fat content varies from less than 1 to 14%, the fat content has been measured either by NMR on fresh tissue, NMR on dried tissue, or by the use of solvent extraction determining the content of raw fat [Foss-let fat analyser (AOAC Official Method 976.21]. Comparison of the three methods for determination of the fat content shows satisfactory agreement between the different methods. On six samples of minced pork meat, the fat and moisture content have been determined. The total fat content was determined by NMR both on fresh and dried tissue. The moisture content was determined by NMR of fresh tissue and by drying of the tissue. The different methods for determining fat and moisture content agreed for the minced pork samples. PMID- 22060864 TI - Sequence analysis of mitochondrial 12S rRNA gene can identify meat species. AB - In this study, sequence analysis of mitochondrial 12S rRNA has been applied for meat species identification. The procedure involves polymerase chain reaction (PCR) amplification of a fragment of mitochondrial (mt) 12S rRNA gene and sequencing of amplicons. Amplified product of mt 12S rRNA gene was 456 bp in size. Species sequenced include cattle (Bos indicus), buffalo (Bubalus bubalis), sheep (Ovis aries), goat (Capra hircus) and mithun (Bos frontalis). Sequences were compared with the reported sequences of low land anoa (Bubalus depressicornis), yak (Bos grunniens) and pig (Sus scrofa). There was no effect of routinely used additives or cooking temperature (72, 90, 120 and 180 degrees C) on the efficacy of PCR amplification. The closely related species like cattle and buffalo, sheep and goat could also be differentiated decisively by sequence analysis. Sequencing and analysis of mt 12S rRNA gene was, hence, found to be an ideal, authentic and unambiguous qualitative method for meat species identification. PMID- 22060865 TI - Beef carcass contamination in a slaughterhouse and prevalence of resistance to antimicrobial drugs in isolates of selected microbial species. AB - Meat contaminating bacteria may be the direct cause of foodborne diseases and represent a potential cause for the drug resistance of human pathogenic agents. The prevalence and resistance to 17 antimicrobial drugs of isolates of selected bacterial species were investigated in 70 swabs of beef carcasses and 70 subsequent samples of beef meat. Molecular techniques (coagulase gene typing Staphylococcus aureus and original gene typing Escherichia coli) were used in the differentiation of isolates. Carcasses were already contaminated after evisceration, least frequently with S. aureus strains (7.5% of samples), most frequently with coagulase-negative staphylococci strains (52.2% of samples). During carcass processing, contamination with resistant or polyresistant strains of S. aureus and E. coli significantly increased (P<0.01). Gene typing isolates of S. aureus and E. coli indicated that the strains probably originated in the processing plant. PMID- 22060866 TI - Effect of pasture vs. concentrate feeding with or without antioxidants on carcass characteristics, fatty acid composition, and quality of Uruguayan beef. AB - Thirty Hereford steers were finished either on pasture (n=10) or concentrate (n=20) to determine dietary and antioxidant treatment effects on carcass characteristics, fatty acid composition, and quality of Uruguayan beef. Half of the steers finished on concentrate were supplemented with 1000 I.U. vitamin E head(-1) day(-1) for 100 days. Postmortem vitamin C was added to ground beef (0.05% v/w) displayed for 8 days at 2 degrees C. Carcasses from steers finished on concentrate had greater (P<0.05) carcass weight, conformation, degree of finishing, fat depth, and ribeye area than pasture finished animals. Carcasses from pasture-fed steers showed darker (P<0.05) longissimus color and yellower (P<0.05) fat at 24 h postmortem than concentrate-fed. Initial longissimus Warner Bratzler shear force (WBSF) values were similar (P>0.05) between pasture- and concentrate-fed animals. However, beef from pasture-fed cattle had lower (P<0.05) WBSF values at 7 and 14 days postmortem. Longissimus alpha-tocopherol concentrations were greater (P<0.01) for pasture- and concentrate-fed animals that were supplemented with vitamin E compared to concentrate-fed. Steaks from pasture-fed and vitamin E supplemented cattle had similar (P>0.05) TBARS values, which were lower (P<0.05) than steaks from concentrate-fed steers during 21 days of display. Ground beef from vitamin E supplemented steers had the lowest TBARS values; whereas samples from pasture-fed animals had the lowest lipid stability with higher TBARS levels than other treatments. Vitamin C addition to ground beef did not (P>0.05) reduce lipid oxidation. Vitamin E supplementation of concentrate fed cattle had no effect (P>0.05) on color stability of ground beef or steaks. The a(*) (redness) and b(*) (yellowness) values were higher (P<0.05) when vitamin C was added to ground beef. Longissimus fatty acid content of concentrate-fed animals was twofold greater (P<0.01) than pasture-fed. The percentages of C14:0, C16:0, and C18:1 fatty acids were higher (P<0.01) in the intramuscular fat of concentrate-fed steers, whereas pasture-fed cattle showed greater (P<0.01) proportions of C18:0, C18:2, C18:3, C20:4, C20:5, and C22:5. Total conjugated linoleic acid (CLA) and CLA isomer c9t11 were higher (P<0.01) for pasture- than concentrate-fed cattle. Vitamin E supplementation of concentrate-fed steers increased lipid stability of ground beef and steaks, but was unable to improve color stability; whereas vitamin C addition to ground beef increased color stability without altering lipid oxidation. Finishing cattle on pasture enhanced the unsaturated fatty acid profile of intramuscular fat in beef including CLA and omega-3 fatty acids. PMID- 22060867 TI - Changes in composition and functional properties of proteins and their contributions to Nham characteristics. AB - Changes in composition and functional properties of proteins during fermentation of Nham, a Thai-fermented sausage, were studied. An alkaline-soluble fraction constituted a major protein component of Nham. The amount of each protein fraction in Nham varied, depending on the fermentation time. As fermentation proceeded, the progressive decrease in sarcoplasmic and myofibrillar protein fractions was accompanied by an increase in the alkaline-soluble fraction and non protein constituents (P<0.05). Slow pH lowering to pH 4.6 during fermentation as a result of bacterial growth and accumulation of lactic acid affected the molecular conformation of the muscle proteins and resulted in changes in protein functional properties. The acid produced resulted in changes in solubility, water binding capacity, textural properties, and color characteristics. Proteolysis of Nham proteins occurred during fermentation, resulting in increases in TCA-soluble peptides and free alpha-amino acids, which may contribute to the taste and aroma of Nham. PMID- 22060868 TI - Meat and carcass quality from Peruvian llama (Lama glama) and alpaca (Lama pacos). AB - An experiment based on 20 llama males and 40 alpaca males reared in Peru has been carried out with the aim to evaluate the live growth performances, carcass quality, the nutritional characteristics of meat from animals slaughtered at 25 months of age, and to determine the physical and chemical parameters of meat obtained from these animals. The live body weights registered during the 25 months of the experiment were significantly lower in alpaca compared with llama. In llama carcasses were significantly higher both warm and cold carcass weight (P<0.001) but dressing percentage was higher in alpacas (P<0.01). The glycolityc fine-course was very similar both in llama and in alpaca muscle Longissimus Thoracis et Lumborum. Chemical composition of muscle Longissimus Thoracis et Lumborum taken from llama and alpaca carcasses was significantly different (P<0.01) in ash content; cholesterol content was significantly higher (P<0.001) in llama meat compared with alpaca. PMID- 22060869 TI - Effect of muscle type on the rate of post-mortem proteolysis in pigs. AB - Post-mortem proteolysis was examined in muscle homogenates from porcine m. longissimus dorsi (LD), m. semitendinosus (ST), m. semimembranosus (SM), m. vastus intermedius (VI), and m. soleus (S). During post-mortem storage, desmin and troponin-T degraded faster in LD and SM than in ST, VI and S. ST exhibited the same rate of degradation as VI and S. These differences could not be explained solely by differences in fibre type distribution, indicating that other muscle-specific traits independent of fibre type determine myofibrillar degradation post-mortem. Thus, the rate of post-mortem proteolysis seems to depend more on muscle-to-muscle variations than on fibre type composition. PMID- 22060870 TI - Replacement of pile salting by simultaneous brine thawing-salting in Spanish cured ham manufacturing. AB - Salting, is one of the fundamental operations in Spanish cured ham manufacturing, and is basic in order to preserve the product throughout its processing and storage. Pile salting is the method traditionally employed to accomplish this step. The use of frozen raw material has become quite frequent in the industry, and it implies a preliminary thawing step in a cold chamber. The aim of this study is the analysis of the first step in ham production (salting) and the influence of simultaneous brine thawing/salting and vacuum impregnation in the salting stage of Spanish cured ham. The results indicated a reduction in the salting time when using the brine thawing/salting method, which was performed together with vacuum impregnation. Further studies need to be done in order to fully understand the influence of these new salting methods on the following manufacturing steps and the final quality characteristics. PMID- 22060871 TI - A second mutant allele (V199I) at the PRKAG3 (RN) locus- I. Effect on technological meat quality of pork loin. AB - The effect of three alleles (RN(-), rn(+) and a second mutant allele V199I, denoted rn*) at the PRKAG3 (RN) locus on such meat quality traits as pH, internal reflectance (FOP), Warner-Bratzler shear force, water-holding capacity and cooking loss were studied. M. longissimus dorsi (LD) from a total of 334 crossbreed pigs, entire males and females, Hampshire (H) and Finnish Landrace (L) of three combinations H * LH, LH * H and LH * LH, were used. The PRKAG3 alleles were identified with a DNA test and all possible RN genotypes, RN(-)/RN(-) (23%), RN(-)/rn(+) (24%), RN(-)/rn* (33%), rn(+)/rn(+) (8%), rn(+)/rn* (9%) and rn*/rn* (2%), were found. Water, intramuscular fat, protein and glycogen contents were determined. All the three alleles at the RN locus affected the studied technological meat quality traits of pork loin, except for the internal reflectance 24 h post mortem and the shear force. The RN(-) allele was dominant over the other two alleles, rn(+) and rn*, in LD with regard to ultimate pH, water-holding capacity and cooking loss, giving lower ultimate pH and water holding capacity and higher cooking loss. The rn* allele affected ultimate pH in LD of non-carriers of the RN(-) allele, giving higher ultimate pH. The RN(-) allele was also dominant over the other two alleles in residual glycogen content in entire male pigs, but not in female pigs, where the rn* allele had a glycogen lowering effect. The water content was higher and the protein content lower in LD of all RN(-)/- animals compared with the other genotypes, while no significant differences were found with regard to IMF content. Water-holding capacity, cooking loss and shear force were higher in LD of entire males compared with females. PMID- 22060872 TI - A second mutant allele (V199I) at the PRKAG3 (RN) locus-II. Effect on colour characteristics of pork loin. AB - Three alleles at the PRKAG3 (RN) locus that influence the glycogen content of pork were found to be segregating in Hampshire*Landrace crossbred pigs, RN(-), rn(+) as well as second mutant allele V 199I (here denoted rn*). The effect of these three alleles on ultimate pH, pigment content, internal reflectance (FOP), surface colour measured by tristimulus colorimetry (L*, a*, b*) and fractions of deoxymyoglobin (Mb), oxymyoglobin (MbO(2)) and metmyoglobin (MetMb) of pork loin was studied. Moreover, the effect of sex, entire male versus female pigs, on these traits was also analysed. The three PRKAG3 alleles affected ultimate pH, internal reflectance, colour and distribution of myoglobin derivatives of pork loin, while the pigment content was not influenced. Ultimate pH values of loins from the three genotypes were found to be in the order RN(-)/- genotypes rn(+)/rn(+) genotype=rn(+)/rn* genotype=rn*/rn* genotype. The RN(-) allele was dominant resulting in higher redness (a* value) and yellowness (b* value), while the rn* allele tended to result in lower redness and yellowness compared with the rn* allele. The RN(-) allele was dominant over the rn* allele in lightness (L* value) giving a lighter colour. Surface colour differences were mainly explained by differences in the distribution of the myoglobin derivatives. Finally, surface lightness was higher and pigment content, redness and fraction of MbO(2) lower in loin from entire males compared with females. PMID- 22060873 TI - Concentrations in beef and lamb of taurine, carnosine, coenzyme Q(10), and creatine. AB - Levels of taurine, carnosine, coenzyme Q(10), and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q(10) is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q(10), but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q(10) and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 degrees C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine (P<0.001), but a slight increase in coenzyme Q(10). There was also a four-fold increase in creatinine, presumably due to its formation from creatine. It is concluded that biologically, and possibly nutritionally, significant levels of taurine, carnosine, coenzyme Q(10), and creatine are present in beef and lamb, but that these levels vary between muscles, between animals, and with cooking. PMID- 22060874 TI - Lipid composition of the intramuscular fat of beef from Spanish cattle breeds stored under modified atmosphere. AB - The lipid composition of intramuscular fat from 30 young bulls of 5 Spanish cattle breeds (Asturiana de los Valles, Morucha, Parda Alpina, Pirenaica and Retinta) was studied. Steaks from each shortloin were packaged in 60% O(2), 30% CO(2) and 10% N(2) and aged for 0, 5, 10 and 15 days. Lipid classes obtained by thin layer chromatography and total fatty acids obtained by gas chromatography were evaluated. Meat from Asturiana de los Valles had high PL and C contents, and low TG contents that reflected its low intramuscular percentage content. This breed showed high FFA content that likely originated from lipolysis of PL. The main breed effect was due to the low intramuscular fat content observed in the Asturiana de los Valles. After 5 days, FFA decreased because they were probably transformed into other compounds. The Morucha breed may have a genetic predisposition for depositing MUFA, and the high MUFA and C14:0 values observed in the Morucha breed were likely due to its high intramuscular fat percentage. Regarding fatty acid composition, no "days of storage" effect was observed for any of the studied fatty acids, except for C18:3omega6 that increased during the first 5 days of storage in Asturiana de los Valles. Concerning the fatty acid composition, Asturiana de los Valles had the highest PUFA/SFA ratio, while Parda Alpina and Morucha possessed low omega6/omega3 ratios but high C22:6omega3 contents. Finally, the presence of C22:6omega3 and 15-CH(3)-C16:0 may be related to higher intramuscular fat contents. PMID- 22060875 TI - Study of the effects of smoke flavourings on the oxidative stability of the lipids of pork adipose tissue by means of Fourier transform infrared spectroscopy. AB - Pork adipose tissue was dry-salted for 24 h and then smoked by immersion in two liquid smoke flavourings for 1, 2 or 3 min. Both unsmoked and smoked pork adipose tissue samples were submitted to oxidative conditions at 70 degrees C in a convection oven with circulating air. Melted lipids of both samples were studied by Fourier transform infrared spectroscopy. Duplicate spectra were collected each day of the experiment by applying a film of melted lipids between two KBr disks. Changes in frequency values of different bands and in ratios between absorbances of some bands allow oxidation degree and oxidative stability of the samples to be determined. The usefulness of this technique for monitoring the oxidation process of pork adipose tissue lipids is shown. The greater oxidative stability of smoked pork adipose tissue samples in comparison with unsmoked samples is proved. PMID- 22060876 TI - PCR-based fingerprinting techniques for rapid detection of animal species in meat products. AB - A reproducible, rapid, and simple method for simultaneous identification of multiple meat species in a single step DNA-based test has been developed based on the generation of species-specific fingerprintings by two different arbitrary DNA amplification approaches (RAPD- and AP-PCR). Samples representative of various species and meat products submitted to different processing conditions were selected to verify the applicability of the techniques. RAPD-PCR fingerprintings allowed the discrimination amongst pork, beef, lamb, chicken and turkey in all cases. Samples corresponding to each species were clustered together at similarity levels ?75%. The DNA profiles consisted of a discrete but reproducible number of bands, which made possible the interpretation of the results by simple visual inspection. AP-PCR also allowed identification of the five tested species in every sample although more complex patterns were generated, including some low intensity bands. In both cases, a ramp time between annealing and extension temperatures was introduced to achieve good reproducibility. Overall, the simplicity of RAPD-PCR patterns could make this technique suitable for meat authentication in routine analysis. PMID- 22060877 TI - Bacterial populations associated with meat from the deboning room of a high throughput red meat abattoir. AB - Developing countries are faced with high incidences of food poisoning outbreaks, with obvious economic consequences. In highly perishable foodstuffs such as fresh red meat the threat of food poisoning is particularly intense. In this study, red meat samples were collected from a deboning room of a high throughput abattoir. The samples were analysed for the presence of Bacillus cereus., Staphylococcus aureus., Pseudomonas spp., Listeria monocytogenes., Escherichia coli and Salmonella spp. The aerobic plate counts as well as Enterobacteriaceae were also enumerated. Almost without exception the counts exceeded the microbiological guidelines for raw meat as proposed by the South African Department of Health. The average B. cereus count over the sampling period was 8.32 * 10(3) cfu, g ( 1), for S. aureus and Pseudomonas spp. 1.72 * 10(5) and 1.7 * 10(5) cfu g(-1) respectively and for E. coli 3.4 * 10(5) cfu g(-1). Sixty percent of the samples were positive for presumptive Salmonella spp. while 52% of the samples tested positive for the presence of L. monocytogenes. The aerobic plate and Enterobacteriaceae counts were 1.7 * 10(7) and 4.6 * 10(6) cfu g(-1), respectively. The data highlighted the need for a more systematic approach to ensuring safe food through implementing quality control methods to prevent the entry and proliferation of pathogens in meat and meat products, especially during processes with a high degree of handling, such as deboning. PMID- 22060878 TI - Generation of flavour compounds in fermented sausages-the influence of curing ingredients, Staphylococcus starter culture and ripening time. AB - The volatile profiles of fermented sausages made with either Staphylococcus xylosus or Staphylococcus carnosus starter cultures were studied with regard to the influence of salt concentration, ripening time and three different combinations of curing ingredients-nitrate, nitrite or nitrite/ascorbate. Emphasis was laid on volatile compounds originating from degradation of branched chain amino acids. Volatile compounds were collected using dynamic headspace sampling and were identified by gas chromatography/mass spectrometry (GC/MS). Development in water activity, water loss and pH was monitored throughout maturation. Curing salts had a pronounced effect on the level of volatile compounds. In particular, curing with nitrate instead of nitrite resulted in a striking difference. Generally, nitrate increased the level of volatile compounds compared to nitrite, whereas ascorbate had only a small influence. The concentration level of NaCl had a considerable effect on the amount of volatile compounds but the effect was highly related to the ripening stage. Most compounds, but not all, increased in concentration as ripening proceeded. Major differences in the development of volatile compounds were observed depending on whether S. xylosus or S. carnosus were used as starter culture. In particular the effects of nitrate was much more predominant in the sausages made with S. carnosus than S.xylosus. PMID- 22060879 TI - Evaluation of surimi, fat and water content in a low/no added pork sausage formulation using response surface methodology. AB - Response surface methodology (RSM) was employed for simultaneous analysis of the effects of added surimi (0-40%), fat (5-30%) and water (10-35%), on the physical, textural and sensory characteristics of fresh breakfast pork sausages. Experimental design allowed for evaluation of potential interactive effects between these ingredients. Sausages were evaluated for texture, colour, water holding capacity (WHC) and sensory attributes. Three optimum recipes, R1 (25.3% surimi, 22.2% fat, 12.7% water, 25.3% pork), R2 (12.2% surimi, 5.5% fat, 38.7% water, 33.2% pork) and R3 (25.3% surimi, 6.3% fat, 28.5% water, 25.3% pork), were determined and these were evaluated against a full-fat commercial control (R4). Force values of R1 were not significantly different to R4, however, force values for R2 and R3 were lower (P<0.001). No significant differences were observed between R1, R3 and R4 for visual colour or sensory acceptability scores throughout the study, whereas scores for R2 were lower. Sensory analysis indicated that R2 had lower scores for texture (P<0.01), chewiness (P<0.01), acceptability (P<0.01), flavour (P<0.05) and preference (P<0.01). Results from this study suggest that it is possible to successfully replace pork meat with functional fish proteins in the manufacture of sausage type products. PMID- 22060880 TI - Use of bacteriocin-producing starter cultures of Lactobacillus plantarum and Lactobacillus curvatus in production of ostrich meat salami. AB - Ostrich meat salami was produced by using Lactobacillus plantarum strain 423 and Lactobacillus curvatus strain DF126. The strains produce the bacteriocins plantaricin 423 and curvacin DF126, respectively. The specific activity of plantaricin 423 in MRS broth at 30 degrees C increased as the pH decreased from 6.5 to 3.5, but activity subsequently decreased. The activity of curvacin DF126 increased under the same conditions, but remained stable for the duration of the growth cycle. Maximum curvacin DF126 and plantaricin 423 activity levels were recorded at a culture pH of around 4. The spectra of antimicrobial activity recorded for plantaricin 423 and curvacin DF126 were similar. Neither of the two bacteriocins inhibited the growth of Micrococcus sp. MC50 and did not have any inhibitory effect on either of the producer strains. Curvacin DF126 and plantaricin 423 inhibited the growth of L. monocytogenes in salami meat. However, after 15 h of fermentation the viable count of L. monocytogenes LM1 increased, probably due to a decrease in activity of the bacteriocins and/or the development of resistant bacterial cells. This is the first report on the inhibition of L. monocytogenes in ostrich meat salami by using bacteriocinogenic starter cultures. PMID- 22060881 TI - Ice VI freezing of meat: supercooling and ultrastructural studies. AB - While "classical" freezing (to ice I) is disruptive to the microstructure of meat, freezing to ice VI has been found to preserve it. Ice VI freeze substitution microscopy showed no traces of structural alteration on muscle fibres compared with the extensive damage caused by ice I freezing. The different signs of the freezing volume changes associated with these two ice phases is the most likely explanation for the above effects. Ice VI exists only at high pressure (632.4-2216 MPa) but can be formed and kept at room temperature. It was found that its nucleation requires a higher degree of supercooling than ice I freezing does, both for pure water and meat. Monitoring of the freezing process (by temperature and/or pressure measurements) is, thus, essential. The possible applications of ice VI freezing for food and other biological materials and the nucleation behaviour of this ice phase are discussed. PMID- 22060882 TI - Use of antioxidants to minimize rancidity in pressurized and cooked chicken slurries. AB - Sodium chloride (5%) and some antioxidants (400 ppm rosemary extract; 2000 ppm acerola extract; 50 ppm ethylenediamine tetraacetic acid (EDTA); 1,000, 2,000, and 5,000 pm of sodium hexametaphosphate or 5 and 10% egg white powder) were added to minced chicken. From these mixtures, slurries were made by mixing with water (1:3) at 15,000 rpm for 30 s at 20 degrees C. Samples were pressurized (300, 500 and 900 MPa for 30 min at 20 degrees C) or cooked (90 degrees C for 15 min). Hexanal was quantified by solid phase microextraction at 1, 3, 6 and 9 days of 4 degrees C storage in contact with air. Hexanal values increased with pressure and storage time. Cooked slurries had higher hexanal contents than samples pressurized at 300 MPa, but lower than those treated at 500 and 900 MPa. Rosemary extract was an antioxidant for pressure-treated samples, but had little effect on cooked ones. Acerola extract was not an effective antioxidant, but EDTA strongly inhibited oxidation. Hexamethaphosphate also showed antioxidant ability. Egg white powder inhibited hexanal generation, which can be a new way for revalorizing egg constituents. PMID- 22060883 TI - Electronic nose for the identification of pig feeding and ripening time in Iberian hams. AB - An electronic nose system to control the processing of dry-cured Iberian ham is presented. The sensors involved are tin oxide semiconductors thin films. They were prepared by RF sputtering. Some of the sensors were doped with metal catalysts as Pt and Pd, in order to improve the selectivity of the sensors. The multisensor with 16 semiconductor sensors, gave different responses from two types of dry-cured Iberian hams which differ in the feeding and curing time. The data has been analysed using the PCA (principal component analysis) and backpropagation and probabilistic neural networks. The analysis shows that different types of Iberian ham can be discriminated and identified successfully. PMID- 22060884 TI - Effect of enrobing and antioxidants on quality characteristics of precooked pork patties under chilled and frozen storage conditions. AB - Enrobed or coated pork patties containing a (50:50) mixture of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) at a level of 100 ppm in the batter mix and meat emulsion were cooked and stored chilled (4+/-1 degrees C) and frozen (-18+/-1 degrees C) for evaluation of quality. Test samples were compared to control patties (neither enrobed nor antioxidant treated). After 35 days of refrigerated storage no significant difference (P>0.05) was found in pH, 2-thiobarbituric acid (TBA) and Warner-Bratzler shear force (WBSF) values between uncoated and treated samples. Similarly, enrobed patties showed no significant (P<0.05) decrease in TBA values compared to control patties, but had lower relative moisture loss at the 45th day of frozen storage. However, control patties had significantly (P<0.05) higher overall shear values than coated patties under the same storage conditions. Coated samples had higher microbial loads but below the acceptable limit. Total plate counts (TPC) in enrobed and control patties were around 3.48 and 3.05 log(10) cfu/g, respectively, whereas in frozen stored samples these numbers were 2.77 and 2.69 log(10) cfu/g at the end of storage. Sensory scores viz appearance and color, flavor, juiciness, texture, and overall acceptability were higher in treated samples than controls during the entire storage period. PMID- 22060885 TI - Method of isolation, rate of postmortem metabolism, and myosin heavy chain isoform composition influence ATPase activity of isolated porcine myofibrils. AB - The objective of this study was to determine the influence of myofibril isolation procedures and myosin heavy chain (MyHC) isoform composition on myofibrillar ATPase activity as related to postmortem muscle metabolism. Myofibrils from the red (RST) and white (WST) portions of semitendinosus muscles were isolated using two different methods (A and B) at 3 min and 24 h postmortem in control (NS) and electrically stimulated (ES) pork carcasses. Comparison of the relative MyHC isoform profiles between the two different myofibril isolation methods and myosin extracts from the RST and WST at 3 min showed that method B myofibrils were more similar to the myosin extract than method A. Myofibrillar ATPase activity remained constant or increased (P<0.01) from 3 min to 24 h postmortem in NS carcasses and decreased (P<0.0001) in ES carcasses. From the RST, method A myofibrils had higher (P<0.0001) ATPase activity compared to method B across sampling time and carcass treatment. In the WST, method A myofibrils had lower (P<0.01) activity at 3 min, were not different at 24 h in NS carcasses, but had higher (P<0.05) activity at 24 h in ES carcasses versus method B myofibrils. Compared to method B, isolation method A biased the isoform profile of myofibril samples more towards faster MyHC (2A and 2X) in the RST and towards MyHC 2X in the WST. Results suggest that the ATPase activity and MyHC isoform profile of isolated myofibril samples are influenced by method of myofibril isolation, postmortem sampling time, and the rate of postmortem metabolism. Thus, differences in MyHC isoform profile and method of myofibril isolation must be taken into account to determine accurately the relationship between myofibrillar ATPase activity and rate of postmortem metabolism. PMID- 22060886 TI - A note on the identification of Rupicapra rupicapra species by polymerase chain reaction product sequencing. AB - To identify meat samples suspected of containing a protected game species (Chamois-Rupicapra rupicapra) Polymerase Chain Reaction (PCR) product sequencing was performed. The amplicon was obtained with a pair of "universal" primers. The results confirm those of Isoelectric Focusing (IEF) on the same samples. PMID- 22060888 TI - The chilled storage life and retail display performance of vacuum and carbon dioxide packed hot deboned beef striploins. AB - Two cooling regimes that complied with the New Zealand meat hygiene requirement that hot deboned meat be chilled to +7 degrees C or less within 24 hr of leaving the slaughter floor were evaluated for the production of chilled table meats. Electrically stimulated hot deboned bull beef half striploins were either vacuum or carbon dioxide packed before being cooled in accordance with either Regime 1 (cool at +5 degrees C for 24 hr, transfer to chiller operating at -1.0 +/- 0.5 degrees C) or Regime 2 (cool at +5 degrees C for 24 hr, hold at 5 degrees C for 6 days, transfer to chiller operating at -1.0 +/- 0.5 degrees C). Striploins were removed from -1.0 degrees C storage 8, 28, 42, 56, 70, 84 and 98 days after slaughter and subjected to microbiological, tenderness, sensory and retail display performance evaluations. Both Regimes 1 and 2 produced meat of acceptable mean tenderness, 8 kgF (MIRINZ Tenderometer) in either vacuum or carbon dioxide packs within 28 and 8 days of slaughter, respectively. However, 70 days after slaughter the first signs of over-ageing became apparent. Steaks from Regimes 1 and 2 maintained acceptable visual appearance during retail display at 5 degrees C for 48 hr and 24 hr, respectively. After these times, the product was judged by the panel to be unacceptable because of its dull dark lean tissue and grey to green discoloration of the fat. Poor colour stability during retail display was mirrored by deterioration of sensory attributes, particularly aroma which is indicative of incipient spoilage. While carbon dioxide packaging in combination with Regime 1 offered an initial microbiological advantage over vacuum packaging, this advantage was not, however, carried over into retail display. Poor colour and sensory stability during retail display suggest that chilled table cuts derived from hot deboned bull beef are more suited to the Hotel-Restaurant Institutional (HRI) trade than supermarket retailing. To serve the HRI, vacuum packed hot deboned bull beef primal cuts processed by Regime 1 appear to be the combination of choice. This combination would enable commercial processors to produce quality table beef with a chilled storage life of up to 70 days. PMID- 22060887 TI - Implications of rapid virological response in hepatitis C therapy in the US veteran population. AB - BACKGROUND: Early predictors of response to hepatitis C virus (HCV) therapy, such as rapid virological response, are valuable for the identification of patients with a higher likelihood of treatment success. AIM: To identify predictors of rapid virological response in a real world setting. METHODS: Using the VA Clinical Case Registry, we identified patients with HCV mono-infection, without liver transplantation, who initiated peginterferon (PEG-IFN) and ribavirin (RBV) in 2007 or 2008 and had HCV RNA testing for RVR. Significant baseline characteristics from genotype specific univariate analyses were used in backwards stepwise models to identify significant independent predictors of RVR. RESULTS: The final cohort consisted of 2424 patients with genotype 1 (G1), 666 patients with genotype 2 (G2), and 419 patients with genotype 3 (G3). Rapid virological response rates were 15% for G1, 71% for G2 and 57% for G3. Sustained virological response rates were significantly higher in patients with rapid virological response than without, increasing from 18% to 52% in G1, 39% to 71% in G2, and 40% to 60% in G3 (P < 0.0001). A baseline HCV RNA < 500,000 IU/mL positively predicted RVR across all genotypes studied. In addition, for G1, Black race, Hispanic ethnicity, aspartate aminotransferase/alanine aminotransferase (AST/ALT) >= 0.6, ferritin >= 350 ng/mL, LDL< 100 mg/dL and diabetes; for G2, BMI >= 30 kg/m(2), platelets < 150 K/MUL, LDL< 100 mg/dL and the use of PEG-IFN alfa-2b; and for G3, AST/ALT >= 1.0, all negatively predicted rapid virological response. CONCLUSION: We found several novel independent predictors of rapid virological response, including BMI, AST/ALT ratio, ferritin, platelets, LDL, diabetes and type of PEG-IFN prescribed, which may be useful in guiding treatment decisions in routine medical practice. PMID- 22060889 TI - Dietary vitamin E effect on color stability and sensory assessment of spoilage in three beef muscles. AB - Effects of dietary vitamin E supplementation (1204 IU/head/day) for 122 days on color stability and microbial load on beef m. longissimus lumborum (LL), m. gluteus medius (GM) and m. psoas major (PM) were studied by subjective and objective evaluation. Color stability of these muscles followed the order LL > GM > PM (p < 0.05). Vitamin E-treated LL, GM and PM showed less metmyoglobin formation, higher a(*) values and lower hue angle values than controls during storage at 4 degrees C (p < 0.05). Sensory evaluation demonstrated that panelists preferred the appearance of vitamin E-treated LL, GM and PM beef steaks. Vitamin E supplementation did not affect total microbial load on LL, PM and GM and did not influence panelists' olfactory assessment of microbial spoilage of beef. Endogenous alpha-tocopherol concentration and lipid stability of microsomal fractions of LL, GM and PM were greater (p < 0.05) in vitamin E treated muscles relative to controls. There was no muscle effect on the pro oxidant activity of microsomes towards oxymyoglobin oxidation (p > 0.05). Oxymyoglobin stability was greater in the presence of microsomal fractions obtained from vitamin E-treated muscle than in those from controls. Dietary vitamin E supplementation delayed oxymyoglobin oxidation in LL, PM and GM muscle and increased the color shelf-life of these muscles without affecting total microbial load. PMID- 22060890 TI - Determination of nitrites in meat systems: An improved procedure. AB - Various analytical methods for nitrite determination in meat products, based on extraction of the preservative through digestion at 60-80 degrees C followed by colorimetric analysis gave relatively poor recoveries (44-65%) when applied to raw beef. An improved procedure was developed based on disintegration and dispersion of beef with sand prior to the extraction step and on the use of a higher concentration of N-(1-naphthyl) ethylenediamine dihydrochloride than normally used. The proposed technique resulted in almost 93% recovery of nitrites and showed a high precision revealed in a variation coefficient of 8̃%. PMID- 22060891 TI - Effect of meat ultimate pH on rate of titin and nebulin degradation. AB - The processes involved in the tenderisation of meat were studied on muscles with a range of ultimate pH values (5.4-7.0), produced by subcutaneous injection of various doses of adrenaline and exercise. The m. longissimus thoracicum et lumborum (LD) was removed from carcasses stored at 10 degrees C and held for 1, 3 or 6 days after slaughter, then frozen until tenderness assessment. The tenderness of meat cooked from the frozen state was determined as the force to shear samples of 10 mm * 10 mm cross-section using a MIRINZ tenderometer. The maximum toughness of 15 kgF occurred at an ultimate pH (pH(u)) of about 6.0, resulting in a curvilinear relationship between tenderness and pH(u) at 1 day post-slaughter. By 6 days post-slaughter, all meat had reached the same low shear value of approximately 3 kgF. SDS-PAGE patterns obtained from samples at 12, 24 and 48 hr post-slaughter showed increasing titin and nebulin degradation over time, with the slowest rate of degradation occurring at pH(u) values 6.0-6.3. Titin and nebulin are known to play an important role in the stabilisation of myofibril structure, and it is suggested that the curvilinear relationship results when pH-dependent titin and nebulin degradation occurs. PMID- 22060892 TI - Color of fresh, frozen and cooked ground beef patties manufactured with mechanically recovered neck bone lean. AB - Mechanical systems that recover lean tissue from beef vertebrae without grinding bone material are in use in major packing plants across the country. Our objective was to determine the effects of mechanically recovered neck bone lean (MRNL) on color stability of fresh, frozen and cooked ground beef patties. Ground beef patties at two fat levels (10 and 20%) and four MRNL levels (0, 15, 30 and 45%) were analyzed for percentage surface metmyoglobin (metMb) and HunterLab L (*) and a (*) values over 12 days of fresh display and 18 weeks of frozen storage. Data were collected for three replications of the experiment. Mechanically recovered neck bone lean caused an increase in surface metMb up to 7 days of retail display; however, patties made with higher levels of MRNL showed a rapid decrease in surface metMb from days 8 to 12. Both the increase and decrease in surface metMb may be due to microbial effects, which were greater at increased levels of MRNL. Patties made with 30 and 45% MRNL showed greater (p < 0.05) surface metMb by 18 weeks of frozen storage than controls; however, patties with 15% MRNL were not different (p > 0.05) than controls. HunterLab L (*) values for cooked patties decreased in a linear fashion (p < 0.01, R(2) = 0.70) as MRNL level increased. PMID- 22060893 TI - Separation and amino acid composition of three troponin components from bovine muscle. AB - Three troponin components were isolated from bovine skeletal muscle, and their molecular weights and amino acid composition were studied. Crude troponin prepared from bovine muscle was purified by DEAE-Toyopearl chromatography. The purified troponin was dissociated in the order of tropopins C, I and T by CM Toyopearl chromatography in the presence of 6 M urea. The molecular weights of troponins C, I and T were 19,500, 23,300 and 40,400, respectively, as determined with SDS-PAGE. The separation of troponin into three components was also achieved using reverse-phase HPLC; however, the elution order of troponins T and C was contrary to that of the cation-exchange chromatography described above. In this study, the amino acid composition of the three troponin components from bovine skeletal muscle was first determined. The amino acid composition of the three troponin components among bovine, rabbit and chicken skeletal muscles showed stronger similarity than that between bovine skeletal and cardiac muscle with a different muscle type. We considered that this method of troponin preparation from bovine muscle must be a very useful technique for investigating the changes in troponin components, especially troponin T, during ageing of beef. PMID- 22060894 TI - Fatty acid content and composition of english beef, lamb and pork at retail. AB - We have determined the fatty acid content and composition of retail samples of meat and assessed them with respect to UK dietary recommendations. Fifty beef sirloin steaks, pork chops and lamb chops were purchased from four supermarkets on separate occasions. The percentage of muscle (boneless basis) in the samples was 84.4 +/- 4.3, 69.8 +/- 7.7 and 78.9 +/- 7.1 for beef, lamb and pork, respectively, with fatty acid contents of 3.84 +/- 1.3, 4.73 +/- 1.66 and 2.26 +/ 0.7 g per 100 g muscle, respectively. Adipose tissue fatty acid contents were 70.0 +/- 8.2, 70.6 +/- 8.6 and 65.3 +/- 9.4 g per 100 g tissue. A range of C20 and C22 polyunsaturated fatty acids (PUFA) was present in the muscle of all three species and pork adipose tissue but their concentrations in lamb and beef adipose tissue were too low to measure. The mean P:S ratios for beef, lamb and pork muscle were (adipose tissue values in parentheses): 0.11 (0.05); 0.15 (0.09) and 0.58 (0.61), and the n-6:n-3 ratios were 2.1 (2.3), 1.3 (1.4) and 7.2 (7.6). We conclude that the muscles of red meat species are a valuable source of PUFA, particularly the C20 and C22 n-3 fatty acids, in the human diet and that, considered as part of a varied diet, the low P:S ratio of the ruminant muscle, the high n-6:n-3 ratio of pork and the total fatty acid contents do not detract significantly from the nutritional value of lean meat. PMID- 22060895 TI - Effect of clenbuterol on productive performance, body composition and muscle biochemistry in the rabbit. AB - Twenty New Zealand White rabbits (INRA 1077 strain) were given a complete and balanced diet including a clenbuterol additive (100 MUg per day) between 70 and 98 days. They were compared with 20 control rabbits. The treatment improved the growth performance (29.90 vs 26.07 g/day), the feed conversion (5.45 vs 6.46 g feed per g gain) and the carcass yield (64.37 vs 61.11%), by decreasing the relative weights of the skin and the digestive tract. Moreover, all organs in which development is precocious, were found to be relatively lighter. The muscle/bone ratio of the carcass was improved (7.56 vs 6.38), resulting in a greater relative development of muscle tissue, without any change in bone tissue weight. Perirenal and interscapular fat percentages in the carcass were reduced (3.23 vs 3.83 and 0.68 vs 0.86, respectively). Clenbuterol, a repartitioning agent, had therefore modified the growth allometry of the organs and tissues. In the hindleg region (Biceps femoris, Tensor fasciae latae, Semimembranosus accessorius), the ultimate muscular pH was increased, (+0.31 pH units on average), while the cooking loss was reduced (24.23 vs 24.88%). In the m. longissimus lumborum, the increase of ultimate pH (+0.31 units of pH), under the effect of clenbuterol, was explained by a relative increase in the oxidative metabolic pathway represented by aldolase/ICDH ratio (246 vs 284) and by a decrease in glucidic content (total glycosyl residues) of muscle (16.6 vs 26.2 MU mol g ). Due to its effects on muscular biology, clenbuterol is thus likely to cause a change in meat quality. PMID- 22060897 TI - Lipolysis in dry-cured ham maturation. AB - Thirty light Parma hams were tested for muscle lipolytic activity (acid and neutral lipase activity) and free fatty acid (FFA) amounts in M. semimembranosus and biceps femoris, during progressive phases (0, 3, 6, 10 months) of dry-cured ham manufacturing. No correlation was found between the activities of acid and neutral lipases in fresh M. semimembranosus, while during processing the activities were positively related (p<0.1), probably due to effects of muscle composition changes on lipolytic activities. In each processing step tested, acid lipase activities were higher in the M. semimembranosus than in the M. biceps femoris, and FFA amounts varied accordingly, the only exception being for the very dehydrated 10-month old M. semimembranosus, which yielded lower FFA than in the corresponding M. biceps femoris. FFAs in the end product correlated positively with acid and neutral lipase activities of green ham, suggesting that FFA production could be influenced by both raw meat properties and muscle composition during processing. PMID- 22060896 TI - Enhanced expression of heme oxygenase-1 and carbon monoxide excitatory effects in oxytocin and vasopressin neurones during water deprivation. AB - A growing body of evidence indiates that carbon monoxide (CO) acts as a gas neurotransmitter within the central nervous system. Although CO has been shown to affect neurohypophyseal hormone release in response to osmotic stimuli, the precise sources, targets and mechanisms underlying the actions of CO within the magnocellular neurosecretory system remain largely unknown. In the present study, we combined immunohistochemistry and patch-clamp electrophysiology to study the cellular distribution of the CO-synthase enzyme heme oxygenase type 1 (HO-1), as well as the actions of CO on oxytocin (OT) and vasopressin (VP) magnocellular neurosecretory cells (MNCs), in euhydrated (EU) and 48-h water-deprived rats (48WD). Our results show the expression of HO-1 immunoreactivity both in OT and VP neurones, as well as in a small proportion of astrocytes, both in supraoptic (SON) and paraventricular (PVN) nuclei. HO-1 expression, and its colocalisation with OT and VP neurones within the SON and PVN, was significantly enhanced in 48WD rats. Inhibition of HO activity with chromium mesoporphyrin IX chloride (CrMP; 20 MUm) resulted in a slight membrane hyperpolarisation in SON neurones from EU rats, without significantly affecting their firing activity. In 48WD rats, on the other hand, CrMP resulted in a more robust membrane hyperpolarisation, significantly decreasing neuronal firing discharge. Taken together, our results indicate that magnocellular SON and PVN neurones express HO 1, and that CO acts as an excitatory gas neurotransmitter in this system. Moreover, we found that the expression and actions of CO were enhanced in water deprived rats, suggesting that the state-dependent up-regulation of the HO-1/CO signalling pathway contributes to enhance MNCs firing activity during an osmotic challenge. PMID- 22060898 TI - Effect of dietary vitamin E supplementation on cholesterol oxidation in vacuum packaged cooked beef steaks. AB - The effect of dietary vitamin E supplementation on cholesterol oxidation in vacuum packaged, cooked, refrigerated and frozen beef steaks, was investigated. Steers (Friesian*Charolais*Black Hereford) were fed diets providing 20 or 3000 mg alpha-tocopheryl acetate/head/day for 135 days prior to slaughter. alpha Tocopherol concentrations in M. psoas major (PM) and M. longissimus dorsi (LD) were significantly (p<0.05) increased by supplementation and were significantly (p<0.05) higher in PM than LD. Cholesterol oxidation (monitored by measuring 7 ketocholesterol formation) increased during refrigerated and frozen storage in some, but not all, groups, and tended to be higher in PM than LD. Dietary vitamin E did not affect 7-ketocholesterol formation in LD, but significantly (p<0.05) reduced concentrations in PM during refrigerated and frozen storage. Supplementation significantly (p<0.05) reduced TBARS in PM and LD, indicating that vitamin E improved oxidative stability in both muscles. The results show that dietary vitamin E supplementation inhibits cholesterol oxidation in vacuum packaged, cooked beef during refrigerated and frozen storage, but may be influenced by muscle type. PMID- 22060899 TI - Prediction of temperature and moisture content of frankfurters during thermal processing using neural network. AB - An artificial neural network (ANN) was developed to predict temperature and moisture content of frankfurters during smokehouse cooking. Fat protein ratio (FP), initial moisture content, initial temperature, radius of frankfurter, ambient temperature, relative humidity and process time were input variables. Temperature at the frankfurter centre, average temperature of the frankfurter and average moisture content (d.b) of the frankfurter were outputs. Network training data were obtained from validated heat and mass transfer models simulating temperature and moisture profiles of a frankfurter. Backpropagation method was used for ANN training. Selection of hidden nodes, learning rate, momentum and range of input variables were important to ANN prediction. The FP was not an important factor in predictions. PMID- 22060900 TI - Bovine muscle glycogen concentration in relation to finishing diet, slaughter and ultimate pH. AB - The aim of this study was to investigate the effects of a high-energy diet provided for a rather short time prior to transportation to slaughter on muscle glycogen concentration on farm, after transportation and after refrigeration of the carcasses. The experiment involved 60 Ayrshire bulls which were fed either a low energy diet of 100% grass silage or a compound feed based diet providing 10.8 and 12.9 MJ of metabolizable energy per kg of dry matter, respectively. Identical setup of 30 bulls was carried out in spring and in summer. Three muscle samples were obtained from the longissimus dorsi and gluteus medius muscles: a biopsy prior to initiation of experimental feeding (B1); another biopsy after 14 days on diet (B2); a post mortem sample at 48 h after slaughter (3) (also M. semimembranosus). Initial resting muscle glycogen concentration affected the responsiveness of glycogen to diet. The more glycogen there was initially the less glycogen increased (r=-0.678, p<0.0001). However, compared to the low energy diet the high energy diet seemed to protect cattle from potentially glycogen depleting stressors such as high temperatures and transportation. The cattle on high energy lost 7+/-4.0 (se) mmol/kg and 23+/-3.9 mmol/kg during transportation in spring (cool weather) and in summer (hot weather), respectively, whereas the cattle on low energy diet lost 16+/-3.8 mmol/kg in spring and 33+/-4.1 mmol/kg in summer. The overall protective effect of high energy diet corresponded to 0.65 pH units. The effects of diet were reflected all the way to ultimate pH values [5.69+/-0.03 (high energy); 5.93+/-0.03 (low energy)] (p<0.0001) and residual glycogen concentrations (p<0.0001). It seems indeed that providing a diet high in energy for a couple of weeks prior to transportation to slaughter is one of the many appropriate measures to take in the fight against bovine dark-cutting. PMID- 22060901 TI - Some effects of residual glycogen concentration on the physical and sensory quality of normal pH beef. AB - The aim of this study was to assess the effects of residual glycogen concentration on the physical and sensory quality of normal-pH beef. Longissimus thoracis et lumborum muscles (n=42) having ultimate pH (48 h) between 5.50 and 5.75 were excised, assayed for residual glycogen concentration and divided into three categories according to the residual glycogen concentration. The categories were ?25 mmol/kg, 25.1-49.9 mmol/kg and ? 50 mmol/kg. One half of every LTL muscle was aged for 28 days. All samples were evaluated for fresh meat colour, drip loss, shear force, thawing and frying losses and fried steak colour as well as sensory attributes of tenderness, juiciness, flavour and overall palatability. The independent significant effects of increasing residual glycogen concentration on the physical and sensory quality of normal-pH-beef were, although numerous, quite modest in magnitude. The water holding variables in the form of decreasing drip loss (p<0.061), increasing thawing loss (p<005), increasing sum of losses in thawing and frying (p<0.05), and decreasing sensory juiciness (p<0.05) were somewhat affected as were decreasing fresh meat redness (Minolta a*) (p<0.005), decreasing shear force (p<0.05) and increasing yellowness (Minolta b*) of the steak (p<0.0001). Beef of the lowest and highest glycogen category were the ones behaving slightly differently from each other, the intermediate category mostly followed the pattern of one or the other. PMID- 22060902 TI - The effect of oxygen level and exogenous alpha-tocopherol on the oxidative stability of minced beef in modified atmosphere packs. AB - The effect of oxygen level (20, 40, 60 and 80%) in modified atmospheres on the oxymyoglobin content of intact and minced beef (M. semimembranosus, SM) was evaluated. There was no significant difference in the oxymyoglobin content of minced SM stored for up to 4 days in modified atmosphere packs containing 20, 40, 60 or 80% O(2). After 7 days, oxymyoglobin in minced SM decreased significantly (P?0.05) with decreasing oxygen level but by day 10 all samples had similarly low oxymyoglobin contents. Lipid oxidation increased significantly (P?0.05) between day 7 and 10 of storage in minced SM stored in modified atmospheres containing 40, 60 or 80% O(2). Oxymyoglobin and lipid oxidation occurred in intact SM but the extent of oxidation was lower than for minced SM. Exogenous alpha-tocopherol, dispersed in olive oil and added to minced SM (300 and 3000 mg alpha tocopherol/kg lipid), had no significant effect on Hunter 'a' values when the samples were stored in low (20%) or high (80%) oxygen atmospheres. Exogenous alpha-tocopherol addition led to a significant reduction in lipid oxidation (P?0.05) in minced SM stored in high but not in low oxygen atmospheres. PMID- 22060903 TI - Postmortem muscle glycolysis and meat quality characteristics of intact male Korean native (Hanwoo) cattle. AB - Five intact Korean bulls weighing about 550 kg were slaughtered to investigate postmortem glycolysis. Histochemical and meat quality characteristics of longissimus dorsi (LD) and psoas major (PM) muscles were made. Postmortem changes in ATP, glucose-6-phosphate and pH demonstrated that the rate of postmortem glycolysis in the PM was significantly faster than in the LD. The shear force to cut cooked PM was significantly lower than that of LD in 1 and 3 day aged samples, but no difference was observed between the two muscles in 7, 15 and 21 day aged samples. During the 21 days of aging, the rate of lipid oxidation, as measured by TBA value, was significantly faster in the PM than in the LD. The result suggests that PM muscle needs less aging time than LD muscle for optimum meat quality. PMID- 22060904 TI - Composition and protein fractions of different meat by-products used for petfood compared with mechanically separated chicken (MSC). AB - Pork by-products (lung lobes, kidneys), chicken viscera (head, feet and viscera) and mechanically separated chicken (MSC) were evaluated for proximate composition, protein distribution and connective tissue. Proximate composition varied among meat by-products and MSC. Pork by-products contained the most crude protein (p<0.05). Low levels of high ionic strength soluble (HIS) proteins were obtained from meat by-products. Pork lungs and chicken viscera contained the greatest amounts of insoluble (IN) proteins (p<0.05). Total collagen values were positively correlated to IN proteins, intramuscular collagen (IMC) and elastin. Types I and III collagen could not be detected by SDS-PAGE for the different meat by-products though collagen solubility appeared to be significant. These results suggest functional property differences between specific by-products are likely when used in petfood product formulations. PMID- 22060905 TI - Functional properties of meat by-products and mechanically separated chicken (MSC) in a high-moisture model petfood system. AB - Contributions to water retention capacity (% WRC) and texture changes were determined for pork by-products (lung lobes, kidneys), chicken viscera (head, feet and viscera) and mechanically separated chicken (MSC) as affected by pH and various salts in a high-moisture model system. The % WRC for meat by-products and MSC was increased by increased pH (4.5-6.8). Pork lungs and MSC had the highest % WRC (p<0.05) among the meat by-products. Meat by-product % WRC was not signifcantly (p>0.05) affected by salt (2%), phosphate (0.3%) or NaOH (0.075%). Chicken viscera had the lowest (p<0.05) mean texture measurements among the meat by-products and MSC. Strong negative correlations (p<0.05) were obtained for texture with total collagen, soluble collagen and high ionic strength soluble (HIS) proteins. These results should be considered for product quality changes when these by-products are used in formulation of high moisture pet food products. PMID- 22060906 TI - Specificity of different anti-myosin heavy chain antibodies in bovine muscle. AB - Muscle fibre types play an important role in bovine meat tenderness, and conditions the speed of ageing. Two generations of myotubes appear during foetal life. Their differentiation results in several types of fibres differing in their contractile and metabolic properties, namely type I fibres and type II fibres (IIA and IIB). Fibre types were identified using antibodies by immunohistochemistry and western-blotting techniques. The aim was to test different antibodies on foetal and adult muscles by these two techniques. Ten monoclonal antibodies reported to be specific to different myosin heavy chain (MHC) isoforms in other species were tested. Only three antibodies were selected: BF.35, specific for I and IIa MHCs, F1.652 specific for foetal MHC and SC.71 an anti II MHCs (IIa and IIb) antibody. The use of these antibodies will enable a more precise characterisation of muscle fibres and will have applications in the study of bovine muscle ontogenesis. PMID- 22060907 TI - Characterisation of indigenous African cattle breeds in relation to meat quality traits. AB - Meat quality characteristics of two Sanga (indigenous) breeds (Afrikaner and Nguni), one indigenous composite breed (Bonsmara), one foreign composite breed (Santa Gertrudis) and two continental breeds (Brown Swiss and Pinzgauer) were compared. Means were adjusted for mean overall subcutaneous fat level (4.7%). Meat tenderness was then related to certain muscle characteristics. Shear force measurements indicated that Santa Gertrudis (SG) meat was significantly less tender than that of the two continental breeds and the three indigenous breeds (P<0.05). Pairwise linear correlations showed that differences found in background toughness (connective tissue) among breeds did not have a significant effect on tenderness. However, higher myofibrillar fragmentation indices, as well as lower white muscle fibre percentages for the three indigenous breeds, especially the two Sanga breeds, proved their potential to produce meat of comparable tenderness to that of continental breeds under specific slaughter and post-slaughter conditions. PMID- 22060908 TI - Production of bacteriocin-like metabolites by lactic acid cultures isolated from sucuk samples. AB - A total of 51 sucuk samples, obtained from different regions of Turkey, were examined for lactic acid bacteria (LAB) strains producing putative bacteriocin like metabolites. For detection of antagonistic activity, agar spot and well diffusion assay tests were used. Lactobacillus sake Lb790, Listeria monocytogenes Li6, Staphylococcus aureus St44 and Escherichia coli NRRL B-3704 were used as indicator organisms. Strains having antimicrobial activity were also tested against Clostridium perfringens 4TTK, Clostridium botulinum type A. 7948, Bacillus cereus NRRL B-3711, Micrococcus luteus NRRL B-4376 and Yersinia enterocolitica type 103. 57 of 424 isolates from sucuk samples were putative producers of bacteriocin-like metabolistes and were identified as the following: 19 Lactobacillus plantarum, 4 L. curvatus, 4 Pediococcus pentosaceus, 3 P. acidilactici, 2 L. pentosus, 2 L. sake, 1 L. delbrueckii, 1 L. rhamnosus and 21 unidentified Lactobacillus spp. P. pentosaceus 416, P. acidilactici 413, 419 and 446, L. curvatus 348, L. plantarum 452 and 495, and Lactobacillus spp. 411 strains have the best potential for use as sucuk starter cultures. PMID- 22060909 TI - A survey of pre-slaughter conditions, halothane gene frequency, and carcass and meat quality in five Spanish pig commercial abattoirs. AB - A total of 116 deliveries, comprising 15,695 commercial pigs delivered to five abattoirs, were surveyed during winter and summer. Information about on-farm fasting, transport duration and stocking density, and lairage time was collected. Cortisol, creatine phospho-kinase (CPK), and lactate, and DNA for halothane genotype were analysed in a subsample of pigs at exsanguination in every journey. Electrical conductivity (PQM) in semimembranosus muscle (SM) and carcass characteristics (Fat-o-Meater and skin damage) were measured in each carcass. pHu of SM was analysed in the laboratory in a subsample in every journey. Carcasses were identified as PSE or DFD based on PQM and pHu, respectively. The n gene frequency ranged among abattoirs from 54 to 8%. Mean lean content was 58.9% for nn, 57.3% for Nn, and 55.8% for NN pigs, though a difference of 2.5% lean was observed between two abattoirs with the same n gene frequency. A straight relationship of the incidence of serious PSE carcasses and n gene frequency was found. The overall incidence of serious PSE and DFD carcasses was 6.5 and 12.5%, respectively. A higher incidence of PSE carcasses was found in summer; in deliveries with <12 h on-farm fasting; with transport stocking densities >0.40 m(2)/100 kg pig; and in transports of <2 h duration. A higher incidence of DFD carcasses was found in winter; with transport stocking densities <0.40 m(2)/100 kg pig; transports of >2 h duration; and lairage times >9 h. Cortisol level in blood increased in winter and decreased after 12-18 h fasting time. A rise in the lactate concentration was observed in pigs transported in high stocking density (<0.40 m(2)/100 kg pig) and for a longer time (>2 h). All blood stress indices increase as increasing lairage time. Carcasses with more skin damage had higher levels of cortisol, CPK and lactate, and higher incidence of DFD meat, compared with non and low skin damage carcasses. PMID- 22060910 TI - Color changes in irradiated cooked pork sausage with different fat sources and packaging during storage. AB - Pork sausages were prepared with lean pork meat, fat from different sources [backfat (BF), corn oil (CO) or flaxseed oil (FO); 10% of lean meat], NaCl (2%), and ice water (10%). The emulsified meat batters were stuffed into casings (3 cm in diameter) and cooked to an internal temperature of 72 degrees C. Cooked sausages were sliced and vacuum- or aerobic-packaged individually. Sausages were irradiated at a 0, 2.5, or 4.5 kGy dose and stored in a 4 degrees C refrigerator for 8 days. Aerobic-packaged, irradiated cooked sausages prepared with BF and FO showed higher Hunter L-values than nonirradiated controls at day 0, but the difference disappeared at day 8. Irradiation increased the Hunter a-value in vacuum-packaged cooked pork sausages regardless of the fat source used, and the increase of the Hunter a-value was dose-dependent. In contrast, the Hunter a value decreased by irradiation in aerobic-packaged cooked pork sausages prepared with BF or FO. The Hunter a-value of cooked pork sausage with aerobic packaging was significantly reduced at day 8. Hunter b-values increased at Day 8 in irradiated cooked pork sausages except for the sausage prepared with CO at 2.5 kGy. Cooked pork sausages prepared with CO were lighter, and sausage prepared with FO was redder and more yellow (p<0.05) in vacuum packaging. PMID- 22060911 TI - Development of technology for the early post mortem prediction of water holding capacity and drip loss in fresh pork. AB - Two different technologies were tested on the slaughterline for their ability to predict drip loss at 24 h, namely near infrared reflectance (NIR) and impedance measurements using a tetra polar measuring geometry at a frequency of 1000 Hz. The results demonstrate that NIR measurements (900-1800 nm) acquired during a 6 min period starting only 30 min post exsanguination through a fibre optic probe in combination with multivariate data analysis can be used for predicting drip loss 24 h after slaughter. A correlation higher than 0.8 was observed for a trial on 99 carcasses measured at a commercial slaughterhouse. The tetrapolar impedance measurements did not perform as well as NIR yielding a correlation of 0.5 with 24 h drip loss. PMID- 22060912 TI - Effects of salt level and high hydrostatic pressure processing on frankfurters formulated with 1.5 and 2.5% salt. AB - The effects of salt level and high pressure processing on cook loss, emulsion stability, colour, textural and sensory characteristics of frankfurters were investigated. Two salt levels (1.5 and 2.5%) and two pressure treatments (150 and 300 MPa) were examined. For each batch a control was set up which was non pressure treated. Cook loss values were significantly decreased in 150 MPa products at the 2.5% salt level compared to controls. Significantly lower cook losses were recorded at the lower salt level after the application of 150 MPa pressure. The stability of the meat emulsions was significantly increased at the lower salt level, especially after 150 MPa pressure. Sensory analysis results for overall flavour acceptability after pressure application of 150 MPa and 300 MPa were similar to control products and panellists preferred products formulated at 1.5% salt after pressure treatment (150 MPa). Hardness, cohesiveness, gumminess and chewiness were also improved after pressure treatment. The results demonstrate that high pressure technology is a viable process that partially compensates for the reduction of salt levels in frankfurters. PMID- 22060913 TI - Control of post mortem pH decrease in pig muscles: experimental design and testing of animal models. AB - From a series of experiments aimed at manipulating and relating the resting levels of glycogen and creatine phosphate (CP) in the live muscle four models were selected to induce different rates and extents of pH decrease post mortem in pig muscle. Model A served as the control, animals being slaughtered under minimal stress, in model B animals were subjected to 10 min treadmill exercise at 3.8 km/h immediately prior to stunning, in model C, animals were given 0.2 mg adrenaline/kg live weight 16 h prior to slaughter, and in model D they were given 0.3 mg adrenaline/kg live weight 16 h before slaughter and subjected to 5 min of treadmill exercise immediately before stunning. After slaughter, the decline in pH and temperature post mortem was recorded in M. longissimus dorsi (LD), M. biceps femoris (BF), M. semimembranosus (SM) and M. psoas major (PM) from 1 min to 24 h after bleeding. Significant differences in ultimate pH and the time course of pH decrease were observed, both as an effect of model as well as type of muscle. No differences in ultimate pH between model A and model B were observed in any of the muscles. Ultimate pH in the C and the D models were significantly higher than in A and B. In the B model lower pH values were observed from 1 min to 6 h post bleeding compared to the other three models. No differences in rate of pH decrease were observed between the A and the B models in any of the muscles. Within the A model no differences in ultimate pH between muscles were seen, indicating that the frequently observed differences in ultimate pH are caused by environmental factors rather than by differences in physiological and morphological characteristics. The exercise bouts caused elevated temperatures during the first hour after bleeding (model B and D). The BF muscle in all the models displayed the fastest rate of pH decrease and SM the slowest; a slower rate of temperature decline occurred in the BF than in the SM. PMID- 22060915 TI - The regulation of N-methyl-D-aspartate receptors by Src kinase. AB - Src family kinases (SFKs) play critical roles in the regulation of many cellular functions by growth factors, G-protein-coupled receptors and ligand-gated ion channels. Recent data have shown that SFKs serve as a convergent point of multiple signaling pathways regulating N-methyl-d-aspartate (NMDA) receptors in the central nervous system. Multiple SFK molecules, such as Src and Fyn, closely associate with their substrate, NMDA receptors, via indirect and direct binding mechanisms. The NMDA receptor is associated with an SFK signaling complex consisting of SFKs; the SFK-activating phosphatase, protein tyrosine phosphatase alpha; and the SFK-inactivating kinase, C-terminal Src kinase. Early studies have demonstrated that intramolecular interactions with the SH2 or SH3 domain lock SFKs in a closed conformation. Disruption of the interdomain interactions can induce the activation of SFKs with multiple signaling pathways involved in regulation of this process. The enzyme activity of SFKs appears 'graded', exhibiting different levels coinciding with activation states. It has also been proposed that the SH2 and SH3 domains may stimulate catalytic activity of protein tyrosine kinases, such as Abl. Recently, it has been found that the enzyme activity of neuronal Src protein is associated with its stability, and that the SH2 and SH3 domain interactions may act not only to constrain the activation of neuronal Src, but also to regulate the enzyme activity of active neuronal Src. Collectively, these findings demonstrate novel mechanisms underlying the regulation of SFKs. PMID- 22060916 TI - Application of different scaffolds for bladder wall regeneration: the bladder as a natural bioreactor. AB - OBJECTIVES: We investigated the potential of different scaffolds for in vivo construction of bladder muscular and urothelial wall. Bladder wall was used as a bioreactor to create a model of the natural environment for cellular interactions, growth, and differentiation. METHODS: Forty rabbits were divided into 10 groups. Different scaffolds were implanted between bladder mucosa and seromuscular layer. Scaffolds used in each group were one layer or a three layered combination of tissue-engineered pericardium (TEP), biofilm, and polyglycolic acid (PGA). In all groups, a biopsy of full thickness of bladder was dissected. Muscular and urothelial layers were separated and minced into small fragments. Fragments were seeded above the urothelial layer and urothelial fragments were placed on the scaffold under the seromuscular layer. One group served as control and no scaffold was inserted between the separated bladder layers. After 2 and 6 weeks, biopsies were performed for histologic examinations (trichrome, smooth muscle alpha-actin, and pancytokeratin AE1/AE3, CD34, CD31). RESULTS: Histopathological examinations showed granulomatous reaction and severe inflammation in biofilm-containing groups. Samples with TEP alone and with PGA coated TEP as scaffolds revealed more organized bladder wall in two different layers with mature urothelial and smooth muscle cells. The number of CD34+ cells and CD31+ microvessels increased continuously during 6 weeks. CONCLUSIONS: Our results demonstrated the effective role of PGA-coated TEP as a potential scaffold for muscular and urothelial fragment seeding in bladder wall acting as a natural bioreactor. Biodegradable scaffolds could be helpful in association with acellular matrices to optimize the cell attachment and in vivo bladder wall construction. PMID- 22060917 TI - Metmyoglobin reducing activity. AB - Meat colour is a major factor that influences the purchase decision by consumers. Many intrinsic and extrinsic factors contribute to the final colour of meat. The role of the MetMb reducing system in maintaining meat colour has been controversial and a considerable amount of work has been published since [Giddings, G. G., 1974. Reduction of ferrimyoglobin in meat. CRC Critical Reviews in Food Technology 5, 143-173] classic review. Historically, the activity of MetMb reductase was classified under different names, for example, diaphorases, aerobic and anaerobic reducing systems, cytochrome b(5) MetMb reductase, and NADH dependent metmyoglobin reducing enzyme system. Several techniques have been proposed to measure the enzyme activity including reflectance spectrophotometry and absorbance spectrophotometry. However, the variations in the reductase systems and techniques used to measure them have yielded inconsistent results from different investigators. This review seeks to characterize the current understanding of metmyoglobin reduction in meat especially with reference to recent developments in this area. Because many systems (different enzymatic systems and non-enzymatic systems) have been reported to reduce MetMb, the term MetMb reductase is not appropriate to be used to reflect "the MetMb reducing activity" in meat. The need for a standardized approach for measuring MetMb reduction is discussed in order for future research to ensure a greater understanding of this important reaction. PMID- 22060918 TI - Lipid oxidation of beef fillets during braising with different cooking oils. AB - Effects of braising without oil and with different cooking oils (olive oil, corn oil and partially hydrogenated plants oil) on the susceptibility to lipid oxidation in beef fillets (psoas major) were evaluated. The beef fillets were pan fried without oil or with the respective oils for five min, followed by 90 min steam cooking (braising). Lipid oxidation status of the samples and the cooking residues was evaluated by peroxide value (PV), acid value (AV), p-Anisidine value (p-AnV), as well as the alteration of the tocopherol content. Total lipids and the individual fatty acid pattern were analyzed in order to determine the impact of the frying medium as well as the cooking procedures on the fat of the braised samples. The decrease in PV simultaneous with the significant increase in p-AnV indicated the progression of lipid oxidation. Tocopherol and fatty acid contents of all the investigated samples exhibited modifications mainly due to the influence of the frying medium and braising process. Although there was a significant change in lipid oxidation parameters, there is no risk in consuming such braised meat. PMID- 22060919 TI - Use of the DNA Comet Assay to detect beef meat treated by ionizing radiation. AB - The DNA Comet Assay has been described as a rapid and inexpensive screening test to identify radiation treatment of food. In this work, this method was applied to detect the treatment of beef meat pieces either by gamma rays or electron beam. The dose levels were 2.5, 4.5, and 7.0kGy for chilled samples, and 2.5, 4.5, 7.0 and 8.5kGy for frozen samples. The analyses were made over periods of 15 and 30 days after irradiation for the chilled and frozen samples, respectively. The effects of gamma rays and electron beam on DNA migration in the test were similar. The DNA Comet Assay, under neutral conditions, made it easy to discriminate between irradiated and non-irradiated beef. PMID- 22060920 TI - Benchmarking value in the pork supply chain: Characterization of US pork in the retail marketplace. AB - Retail pork from eight US cities was obtained for quality and palatability evaluations. Boneless pork loin chops were classified into one of three quality categories - "high," "average," or "low" - with higher quality chops possessing more desirable color, marbling, juiciness, and shear force characteristics than lower quality chops. Loin chops that were enhanced (injected with solution to improve juiciness and/or tenderness) had higher (P<0.05) pH, less purge and cook loss, and higher palatability ratings compared to non-enhanced chops. Hams compared by their protein fat free (PFF) classifications showed that ham and water product received the highest (P<0.05) ratings for juiciness and tenderness, and ham with natural juices received the highest (P<0.05) texture, ham flavor intensity, and smoke flavor ratings. Bacon was compared by price/brand categories; however, the highest priced, national branded bacon (US$12.03/kg) was similar (P>0.05) for most quality and all palatability traits to the lowest priced, national branded bacon (US$6.47/kg) and the store branded bacon (US$8.30/kg) even though retail prices differed widely. Overall, there were tremendous ranges in values for these products indicating that retail pork is quite variable and that efforts to improve the quality and consistency of it must continue. PMID- 22060921 TI - Preference structure for lamb meat consumers. A Spanish case study. AB - There is a current tendency in the European Union member countries to cut down on meat consumption. This tendency is not due as much to the traditional income price factor, but to other attributes whose influence is gaining relative importance. Some of them are: quality, image, health, food safety and changes in people's taste. In addition, the relative importance of different attributes valued by the consumer must be weighed in order to develop marketing strategies which increase lamb meat consumption. In order to determine these preferences, 400 consumers were asked to evaluate different attributes (price, certification, origin, and commercial type) of lamb meat. Results obtained by means of conjoint analysis techniques show that regular consumers as well as occasional ones show a preference for lamb meat type. In this sense, a market share simulation of preferred (suckling and "ternasco") types proved that regular consumers generally prefer suckling lamb to "ternasco" lamb when both are from Castilla-La Mancha. PMID- 22060922 TI - Influence of breed and ageing time on the sensory meat quality and consumer acceptability in intensively reared beef. AB - The meat market is very concerned about the influence of ageing on beef quality. However, not many studies have analysed the possible influence of the intrinsic factors (individual, age, sex, body condition, breed, etc.), on the development of the ageing process. The purpose of this study was to assess the influence of breed on the sensory characteristics of the meat throughout the ageing time, using a trained sensory panel and a consumer test. Forty entire males of four breeds, which represented different biotypes (dairy: 10 Spanish Holstein; dual purpose: 10 Brown Swiss; meat type: 10 Limousin; high muscularity: 10 Blonde d'Aquitaine) were analysed. Animals were weaned at seven months on average (except Holstein calves, which were weaned earlier), and fed intensively. Each breed was slaughtered at its usual commercial live weight, according to the market requirements. The m. Longissimus thoracis et lumborum (between T6 and L6) was cut, vacuum packaged and aged for 1, 3, 7, 14, 21 and 35 days. Cooked samples were evaluated by 8 panellists and 200 consumers. Breed had a significant influence on tenderness (p<0.001) and on the quantity of residue after chewing for panellists (p<0.01), but there was a significant interaction between breed and ageing time for tenderness. Long ageing times (more than seven days) tend to reduce differences among breeds in textural characteristics. Ageing had a very important effect on tenderness (p<0.01) and also on some odour and flavour characteristics evaluated by the panel. Taking into account the results obtained in the consumer test, the consumption of the Limousin meat may be recommended at shorter ageing times, meanwhile Blonde d'Aquitaine, Holstein and Old Brown Swiss meats would need a longer ageing period to obtain an optimum acceptance by the consumer. PMID- 22060923 TI - Colour stability, under simulated retail display conditions, of M. longissimus dorsi and M. semimembranosus from steers given long-term daily exercise and supplemented with vitamin E. AB - The objective was to determine if exercise has a negative impact on the colour stability of beef and if dietary vitamin E (VE) supplementation could counteract any negative effect. Steers were not exercised or were walked 4.41km/day for 18 weeks. Within exercise treatment animals consumed, on average, either 450 or 1050IU/day of VE. Muscle alpha-tocopherol increased (P=0.004) from 2.35 to 3.15MUg/g with VE supplementation. Following ageing M. longissimus dorsi (LD) and M. semimembranosus (SM) steaks were packaged under 80%O(2):20%CO(2) and stored at 4 degrees C. The LD of exercised steers was more red and more saturated (both P<0.05) after 0 and 2 days of storage than LD of unexercised steers. While redness of both muscles decreased over the display period, LD retained a higher redness than SM from day 2 to 7 (P<0.05). Colour shelf-life of LD was extended by 0.75 days, to 3.25 days, due to VE supplementation. PMID- 22060924 TI - Meat mixture detection in Iberian pork sausages. AB - Five homogenized meat mixture treatments of Iberian (I) and/or Standard (S) pork were set up. Each treatment was analyzed by NIRS as a fresh product (N=75) and as dry-cured sausage (N=75). Spectra acquisition was carried out using DA 7000 equipment (Perten Instruments), obtaining a total of 750 spectra. Several absorption peaks and bands were selected as the most representative for homogenized dry-cured and fresh sausages. Discriminant analysis and mixture prediction equations were carried out based on the spectral data gathered. The best results using discriminant models were for fresh products, with 98.3% (calibration) and 60% (validation) correct classification. For dry-cured sausages 91.7% (calibration) and 80% (validation) of the samples were correctly classified. Models developed using mixture prediction equations showed SECV=4.7, r(2)=0.98 (calibration) and 73.3% of validation set were correctly classified for the fresh product. These values for dry-cured sausages were SECV=5.9, r(2)=0.99 (calibration) and 93.3% correctly classified for validation. PMID- 22060925 TI - Effects of mechanical treatments and moisture enhancement on the processing characteristics and tenderness of beef semimembranosus roasts. AB - The combined effect of blade tenderization (TD,NTD), pre-massaging (0 and 30min), moisture enhancement and post-injection tumbling (2h) on the chemical, binding and textural characteristics of pre-cooked roasts made from beef top round was investigated. Properties of the beef roasts were determined by measuring processing (i.e., cooking yield, expressible moisture (EM)) and textural characteristics (Warner-Bratzler shear, Kramer shear (KS), texture profile analysis). Brine injection helped to improve the cook yield and had the largest effect on tenderness of semimembranosus muscles. Post-injection tumbling did not significantly improve yield and textural properties of roasts; however, combined with the tenderization, it had beneficial effects on water holding and moisture retention. Pre-tumbling and blade tenderization treatments prior to injection generally were found to be beneficial for textural characteristics; pre-tumbling also tended to improve cook yield, but did not influence EM. However, no synergistic effect between these two variables was observed. An interaction between injection/tumbling and pre-tumbling was observed for KS. There was a significant improvement of KS values of roasts due to pre-tumbling observed for either non-injected roasts or those injected but without tumbling. However, no additional reduction in shear force was observed with pre-tumbling when roasts were tumbled after injection. This suggests that pre-tumbling may not be necessary to ensure more tender roasts when post-injection tumbling is applied, but would be beneficial for non-injected roasts or when tumbling is not applied after injection. PMID- 22060926 TI - Safety and storage stability of horse meat for human consumption. AB - Most horse meat is consumed by humans and/or animals in the region where it is produced. However, horse meat for human consumption is exported in large quantities from the Americas and in lesser quantities from Eastern Europe, to Western Europe and Japan where it is often eaten raw. Horse meat prepared to a good hygienic condition should not be prone to early microbial spoilage, but contamination of the meat with Salmonella and Yersinia enterocolitica may be relatively common, and infection of the meat with Trichinella may occur occasionally. Those organisms from horse meat could cause disease when the raw meat is eaten. Moreover, accumulation of cadmium in horse liver and kidney may render those tissues unsafe for human consumption. PMID- 22060927 TI - Carcass characterisation of seven Spanish beef breeds slaughtered at two commercial weights. AB - A total of 159 bulls representing seven Spanish beef breeds were fed with concentrates, managed in the same conditions and slaughtered at two commercial weights (veal and young-bull). Carcasses were measured and classified in order to characterise the carcass variation in the Spanish beef market and to assess the relationship among carcass measurements and grading. Principal Component Analysis clearly separated commercial types regardless the inclusion of the carcass weight in the input data. Within commercial weights the studied breeds clustered into three groups according to muscular development and carcass classification score: high meat producer breeds (Asturiana de los Valles and Rubia Gallega); medium meat producers (Parda Alpina and Pirenaica); and low meat producers (Avilena, Retinta and Morucha). The perimeter and width of the leg (muscular development) besides the length and width of the carcass basically defined these three carcass types. Conformation was an important trait in explaining variation between breeds because its values were positively correlated with muscular development and carcass compactness. PMID- 22060928 TI - Variations in metabolite contents and protein denaturation of the longissimus dorsi muscle in various porcine quality classifications and metabolic rates. AB - The purpose of the present study was to investigate the variations in metabolite contents and muscle protein denaturation in various porcine quality classifications and metabolic rates. A total of 226 crossbred pigs were evaluated. Samples were classified based on muscle pH(45min) and R-value into fast or normal glycolysing group. Drip loss and lightness (L*) were used to assign samples as PSE, RSE, or RFN pork. Normal-glycolysing PSE pork contained an exceptional amount of initial glycogen and the high level of lactate at 24h postmortem (PM). The initial levels of metabolites related closely with muscle pH, R-value and protein solubility at 45min PM. The fast glycolysing group exhibited severe protein denaturation during the early postmortem period, and among them, fast-glycolysing PSE pork exhibited most pronounced protein denaturation. Via examination of each sarcoplasmic protein fraction, it was found that the bands for fructose-6-phosphate kinase, creatine kinase, triosephosphate isomerase, and myokinase were generally more evident as fainter bands in the fast glycolysing pigs. PMID- 22060929 TI - Lamb meat quality of two breeds with protected origin designation. Influence of breed, sex and live weight. AB - Lamb meat quality of two Portuguese products was examined. The influences of slaughter weight, sex and breed on eating quality were evaluated. Data were obtained from 72 lambs of two different breeds with protected designation origin. In accord with the normal slaughter weight in the region three classes were considered: A: 9-14kg live weight; B: 14-19kg live weight and C: 19-24kg live weight. pH of M. longissimus thoracis et lumborum muscle (MTL) was measured 1h and 24h after slaughter. Meat colour was estimated in the M. longissimus thoracis et lumborum muscle (MTL) muscle on the 12th rib using the L*a*b* system. Shear force was evaluated 72h after slaughter. Sensorial analysis was assessed by a trained taste panel of 12 members. The pH values found could be considered within the normal pH range, between 5.5 and 5.9. When the pH measurement was made 24h after slaughter, the heavy lambs had significant higher value than the light lambs. In relation to colour variables, live weight, sex and breed had no effect on the red index (a*). Lightness (L) decreased with increasing live weight and the light lambs had higher yellow index (b*) than the heavier lambs. Shear force increased with live weight and the Bragancano breed had a greater mean shear force than the Mirandesa (7.8 vs. 6.8kg/cm(2)). The heavy carcasses had more flavour intensity than the light ones. Mirandesa lambs had significantly lower values for toughness, stringy and odour intensity than Bragancana lambs. PMID- 22060930 TI - Quantification of calpastatin using an optical surface plasmon resonance biosensor. AB - An immunological biosensor for calpastatin was developed on a surface plasmon resonance based system (Biacore Q). The performance of the biosensor assay was evaluated using ovine and bovine muscle and heart extracts with known calpastatin activity. In addition, the relationship between immunologically detectable calpastatin at 1 day postmortem and shear force at 14 days postmortem was investigated for bovine longissimus dorsi. Calpastatin biosensor results for several experiments were linearly related to calpastatin activity measurements with correlation coefficients ranging from 0.51 to 0.99. The intra- and inter assay CVs were <6% (n=12). During postmortem storage, the amount of immunologically detectable calpastatin decreased faster than the inhibitory activity in the enzymatic assay. Probably, the epitope recognized by the antibody is degraded faster than the inhibitory sites of calpastatin during postmortem storage. Calpastatin content at 1 day postmortem was correlated to shear force at 14 days postmortem (r=0.75). It is anticipated that developments in the near future will allow for at-line calpastatin determinations in beef plants. At present, the calpastatin biosensor assay appears suitable for research purposes where large numbers of samples need to be processed for breed evaluation or selection programs because this assay requires less labor than other methods. PMID- 22060931 TI - Geographical origin and breed discrimination of Apulian lamb meat samples by means of analytical and spectroscopic determinations. AB - With the aim of finding parameters capable of characterizing meat according to geographical origin, twenty-five lamb meat samples from three areas located in Apulia (Southern Italy) were analysed for moisture, ash, fat and protein content, stable isotope ratios ((15)N/(14)N and (13)C/(12)C), major elements (Ca, Mg, Na, K) and trace metals (Zn, Cu, Fe, Cr). (1)H high resolution magic angle spinning (HR-MAS) NMR spectra were also obtained for all the samples. The advantages of the (1)H HR-MAS NMR technique are that sample preparation is easy, since the spectrum is obtained directly on the minced solid sample, and that information is acquired for a large number of metabolites (amino acids, fatty acids, sugars, etc.). The application of multivariate statistical analysis to two data sets containing tissue composition results together with the metals contents and (1)H HR-MAS NMR spectral data together with isotope ratios, respectively, provided in both cases a satisfactory origin differentiation of lamb meat samples. PMID- 22060932 TI - Control of Staphylococcus aureus in sausages by enterocin AS-48. AB - Results presented here are the first contribution on the anti-staphylococcal activity of bacteriocin AS-48 in a model meat sausage system. We have examined bacteriocin application, by inoculation with the enterocin AS-48 producer strain Enterococcus faecalis A-48-32 or by adding a semi-purified bacteriocin preparation. AS-48 inhibits proliferation of Staphylococcus aureus in sausages when added at concentrations of 30 or 40MUg/g, achieving a significant reduction of 2 and 5.31 log units, respectively, in viable counts (CFU/g) of staphylococci with respect to the untreated control. The presence of bacteriocin also had a moderate negative effect on total lactic acid bacteria. AS-48(+) strain was developed well in the meat mixture, producing sufficient amounts of AS-48 (to a maximum of 76-88 arbitrary units/g) to control growth of staphylococci. The best result was achieved with a bacteriocinogenic strain inoculum of 10(7)CFU/g. PMID- 22060933 TI - Effect of age on fatty acid composition of Italian Merino suckling lambs. AB - The present study was undertaken to evaluate the effect of age on lipid content and composition of lamb meat. Thirty suckling ram lambs of the Italian Merino breed, reared according to a traditional semi-extensive management, were slaughtered at 30, 50 and 70 days of age to evaluate total lipids and fatty acid profile in three different muscles: longissimus dorsi (LD), semimembranosus (SM) and quadriceps femoris (QF). Age did not dramatically modify lipid content and composition, even if effects of nutritional interest were observed. Meat from lambs slaughtered at 70 days of age presented the best fatty acid profile, because they had the highest PUFA content and ratio to SFA, as well as the lowest thrombogenic index. The SM muscle had better nutritional quality than the LD and the QF, as a result of a higher PUFA percentage and PUFA/SFA ratio, together with a lower thrombogenic index. These characteristics were also associated with slightly lower amounts of intramuscular lipids and SFA. PMID- 22060934 TI - Effect of different concentrations of carbon dioxide and low concentration of carbon monoxide on the shelf-life of fresh pork sausages packaged in modified atmosphere. AB - This paper reports the effects of different concentrations of carbon dioxide and the presence of low levels of carbon monoxide on quality attributes throughout storage of fresh pork sausages. Four pork forelegs (initial pH 5.5-5.7) were used to prepare a total of 120 fresh sausages, which were packaged in different atmospheres containing (%O(2)/%CO(2)/%N(2)): 0/20/80; 0/60/40; 40/20/40; 40/60/0; 80/20/0; and 0.3% CO/30% CO(2)/rest argon. The packs were stored for 20 days at 2+/-1 degrees C in the dark. Three packs for each atmosphere were opened every 4 days for subsequent analysis of pH, colour CIE L*, a*, b*, TBARS formation, microbial psychotrophic aerobes and sensory discolouration and off-odour. Results showed that increasing concentrations of carbon dioxide promoted oxidation of both myoglobin and lipids, most probably due to its effect of lowering pH. Therefore, preservation of colour and odour of fresh pork sausages packaged in modified atmosphere was better achieved using atmospheres containing low CO(2) concentrations (20%) rather than high (60%). However, their shelf-life depended also on the concentration of O(2); 20% CO(2) with high O(2) (80%) enhanced the red colour, but shortened shelf-life, while 20% CO(2) in the absence of O(2) extended freshness to 16 days. The atmosphere containing 0.3% CO, together with 30% CO(2), maintained the red colour for 20 days, but failed to keep fresh odour longer than 16 days. PMID- 22060935 TI - Moisture adsorption properties and adsorption isosteric heat of dehydrated slices of Pastirma (Turkish dry meat product). AB - Moisture sorption characteristics of dehydrated pastirma were investigated at 15 degrees C, 20 degrees C and 30 degrees C over a water activity (a(w)) range of 0.2-0.9. Sigmoidal (type-II) adsorption isotherms were observed for pastirma. The experimental sorption data obtained were applied to the Halsey, Harkins-Jura, Smith, BET, Henderson, Freundlich and GAB isotherm equations to test fitness of these equations to pastirma. The order of the best fit of sorption data obtained for pastirma at 15 degrees C, 20 degrees C and 30 degrees C in all the range of a(w) studied (0.2-0.9) was Harkins Jura>Halsey>BET>Smith>Freundlich>GAB>Henderson, respectively. In the range a(w) 0.2-0.55, BET model has a better fit than in the range a(w) 0.2-0.9. Isosteric heats of adsorption were evaluated by applying the Clausius-Clapeyron equation to experimental isotherms and decreased with increasing moisture content. PMID- 22060936 TI - Incidence in diverse pig populations of an IGF2 mutation with potential influence on meat quality and quantity: An assay based on real time PCR (RT-PCR). AB - IGF2, insulin-like growth factor 2, is implicated in myogenesis and lean meat content. A mutation in a single base (A for G substitution) of the gene for IGF2 (position 3072 in intron 3) has been recently described as the cause of a major QTL effect on muscle growth in pigs [Van Laere, A. S, Nguyen, M., Braunschweig, M., Nezer, C., Collete, C., & Moreau, L. et al. (2003). Nature, 425, 832-836]. We describe here a rapid assay based on real time PCR (RT-PCR) to detect this mutation. We have evaluated the incidence of the mutation in commercial pig crosses, in three populations of purebred Iberian or Iberian*Duroc crosses, and in cured meat products and wild boars. The incidence of the mutation varies among these groups. Penetrance of the A mutation is about 80% in the commercial population. Purebred Iberian pigs were all homozygous G/G whereas crosses of Iberian pigs were heterozygous (90%) or homozygous A/A (10%). The implications of this gene for the selection of Iberian pigs are discussed. PMID- 22060937 TI - Factors affecting food choice in relation to venison: A South African example. AB - Meat is a universally valued and sought-after source of human nutrition. However, concerns are raised about the health implications of eating too much saturated animal fat. This also applies to South Africa where the high incidence of heart disease and cancer is often linked to consumption of red meat. Despite venison offering a healthy alternative to beef and lamb, its consumption is low. A review of appropriate literature and the perceptions, opinions and preferences of 300 South African consumers resulted in a simplified framework of consumer and market related issues that could influence consumers' preference for wild venison. Consumer-related factors include health considerations, sensory variables, social interactions, familiarity and habit, psychographics and demographics, while the most important market-related issues comprise price, distribution and promotion. An understanding of all these factors is required to better target the promotion of venison as a healthy food choice. PMID- 22060938 TI - Effects of cortisol on muscle proteolysis and meat quality in piglets. AB - The present study was conducted to examine the effects of cortisol on muscle proteolysis and meat quality. Male piglets (n=14) were assigned to one of two treatment groups at 28 days of age. After 7 days adaptation period, each group was fed a commercial diet (86% total digestible nutrients, 21.5% crude protein) or the same commercial diet containing cortisol (120mg/kg diet) for 7 days from 35 days of age. All piglets were slaughtered at 42 days of age. The serum triiodothyronine (T3) concentration, MU- and m-calpain and proteasome activities and the content of easily releasable myofilament, which contains intermediates of the breakdown of myofibrils in the m. longissimus dorsi (LD) at slaughter were measured as parameters of muscle proteolysis. Serum T3 levels and MU-calpain activity were increased (P<0.01), as was the amount of easily releasable myofilament and m-calpain and proteasome activities were higher (P<0.05) in LD from cortisol-treated piglets than from non-treated controls. At 24 h postmortem, LD of cortisol-treated piglets showed higher (P<0.01) drip loss and lighter (P<0.05) color than those of the control. The results clearly show that the administration of cortisol increases serum T3 concentration and muscle proteolysis and reduces productivity and meat quality. PMID- 22060939 TI - Dry fermented sausages elaborated with Lactobacillus plantarum-Staphylococcus carnosus part I: Effect of partial replacement of NaCl with KCl on the stability and the nitrosation process. AB - The effect of partial replacement of NaCl with KCl on the nitrosation process of dry fermented sausages elaborated with L. plantarum + S. carnosus as starter culture was analysed. The Na (+)K (+) ratio decreased from 4.38 in the control to 0.86 in the modified product. The nitrosation process happened in a quicker and more intense way from the beginning of the process onwards. The chemical conversion percentages (nitrosopigments/total pigments * 100) were higher during the whole ripening process in the modified product. This fact agrees with the highest acidification found in the modified products. Also, a reduced degree of pigment oxidation was found. PMID- 22060940 TI - Determination of the flavor attributes of cooked beef from cross-bred Angus steers fed corn- or barley-based diets. AB - Eighteen commercial Angus cross-bred feedlot steers of similar hip height and live weight were randomly assigned to one of three dietary treatment groups: corn , corn/barley, or barleybased diets (n = 6 per treatment). Steers were fed for 102-103 days on their respective diets prior to slaughter. Live animal performance traits, carcass characteristics, total lipid and descriptive flavor and descriptive palatability attributes of beef strip loin steaks were determined. End live weight (P = 0.88) did not differ between dietary treatments. Beef carcasses from steers fed corn-, barley-, and corn/barley-based diets did not differ in hot carcass weight (P = 0.18), ribeye area (P = 0.21), kidney, pelvic and heart fat (KPH) (P = 0.35), and yield grade (P = 0.14). However, adjusted preliminary yield grade was higher (P = 0.03) for carcasses from steers fed corn/barley-based diets than carcasses from steers fed barley as the dietary energy source. These data suggest that carcasses from steers fed barley-based diets were lower in external fat. Quality grade characteristics were not different in beef carcasses from steers fed either corn-, barley-, or a corn/barley-based diet. Cook time (P = 0.37), cooking loss (P = 0.83), descriptive meat palatability attributes (P > 0.27), Warner-Bratzler shear force (P = 0.25), and descriptive sensory flavor attributes (P >= 0.17) did not differ for steaks from steers fed the three diets prior to slaughter. The Japanese have claimed that feeding cattle barley-based high energy diets result in beef with different flavor than when cattle are fed high-energy corn-based diets. These results indicated that the eating quality, tenderness and flavor attributes of beef steaks were not influenced by the dietary grain source fed to young steers in this study prior to slaughter. PMID- 22060941 TI - Taste compounds in chorizo and their changes during ripening. AB - Taste compounds in chorizo-a dry fermented sausage-prepared by both traditional and industrial methods, i.e. D- and L-lactic acid, acetic acid, free amino acids and ATP derivatives, were analysed. Industrial chorizo contained larger amounts of D-lactic, L-lactic and acetic acids, several amino acids (e.g. gamma aminobutyric acid, phenylalanine) and hypoxanthine (Hx) than the traditional one (p < 0.05). The variations in taste compounds during the ripening of chorizo were tracked. D-Lactic and acetic acid increased, as well as most of the amino acids. ATP derivatives showed characteristic changes, IMP decreased on the first day and inosine (Ino) changed gradually to Hx during ripening. The taste compounds contents of garlic and paprika were studied. There was an important contribution of asparagine from spices to the initial mixture of sausage. PMID- 22060942 TI - Volatile compounds in chorizo and their changes during ripening. AB - The volatile compounds extracted from both traditional and industrial chorizo-a dry fermented sausage-were analysed by gas chromatography/mass spectrometry (GC/MS). One hundred and twenty-six peaks were detected relating to volatile extracts of which 115 were identified. The substances identified belonged to several classes of chemical: acids, alkanes, alcohols, aldehydes, sulphur compounds, ketones, esters, ethers, phenolic compounds, aromatic hydrocarbons, lactones, nitrogen compounds, terpenes, chloroform and benzofurane. Among the major compounds isolated were acetic acid, allyl-1-thiol and phenol. Larger quantities of most of the chemical groups were found in industrial compared to traditional chorizo, except for sulphur compounds. Typical breakdown products derived from lipid autooxidation were virtually negligible in chorizo. Of the chemicals isolated, sulphur compounds, phenols, acids, ethyl esters and carbonyls could have particular importance to the overall chorizo flavour. In addition, the changes in the proportions of volatile compounds during the ripening of chorizo were tracked. Most of the volatiles increased during ripening, especially acids, alcohols, esters, phenols, ketones and terpenes. On comparing the distribution of the sulphur compounds observed in chorizo with that of garlic, some noteworthy differences were observed. The reason for these differences is based upon several transformations of the sulphur compounds derived from garlic during the ripening and storage of chorizo. PMID- 22060943 TI - Uptake of alpha-tocopherol in porcine plasma and tissues. AB - The effect of feeding alpha-tocopheryl acetate to pigs on the rate and extent of uptake of alpha-tocopherol in various tissues was investigated. The rate of iron ascorbate-induced lipid peroxidation was also studied. One hundred and eight Landrace * Large White pigs were assigned at random to one of the following barley-based diets: 20 mg alpha-tocopheryl acetate/kg feed for up to 126 days; 20 mg/kg feed to day 91, followed by 200 mg/kg feed to day 126, or 200 mg/kg feed for up to 126 days: Pigs from each group were slaughtered at specified intervals. For pigs fed the diet supplemented with 200 mg alpha-tocopheryl acetate/kg feed, alpha-tocopherol levels increased with increasing supplementation time up to day 126 in all tissues studied. The highest levels of alpha-tocopherol were observed in kidney fat and subcutaneous fat (inner layer) followed by subcutaneous fat (outer layer), liver, lung, heart, kidney, with muscle and brain containing approximately the same level. The alpha-tocopherol concentrations in all tissues examined, from pigs fed 200 mg alpha-tocopheryl acetate/kg feed from weaning to day 126 were greater than those fed the supplemented diet for 35 days. Iron induced lipid peroxidation was reduced by dietary alpha-tocopheryl acetate supplementation, and muscle samples from pigs supplemented for 126 days were significantly (p < 0.05) less susceptible to peroxidation compared to muscle from pigs fed the same supplemented diet for 35 days. PMID- 22060944 TI - Polymerase chain reaction for detection of male tissue in pork products. AB - Economic and organoleptic concerns are in opposition relative to the use of male swine (boars) in many pork products. Polymerase chain reaction (PCR) was used to detect the presence of male tissue in hot boned pork and fresh and cooked sausage products. Two oligonucleotide primers were generated to amplify a male-specific 158 base pair fragment from the Y chromosome. Control experiments verified the specificity of the primers for tissue from male swine only. Dilution studies show that male tissue can be detected down to at least 1:10 000 parts of sow tissue. There was no effect of the addition of spices to the sample (fresh bratwurst) or cooking (50, 70 and 100 degrees C for 15 min) on the efficacy of the assay. These results show PCR to be a reliable, specific and sensitive method for detecting male tissue in pork sausage, that may be of great value for monitoring its presence by meat processors or regulatory agencies. PMID- 22060945 TI - Formulation of a cured meat product by the dewatering-impregnation soaking (DIS) process: Mass transfer study and assessment of product quality. AB - Venison muscle meats were simultaneously salted and dried by soaking in a mixed concentrated solution (salt/corn starch syrup) at a low temperature, a process known as dewatering and impregnation soaking (DIS). Cured products of suitable market quality (in terms of their salt and water content) were obtained with this process. The impregnation of standard curing additives (nitrites and polyphosphates) into the meat product was controlled by mixing these compounds in the concentrated solution. Also, beneficial effects of additives on the physicochemical, microbiological and organoleptic characteristics of the product are confirmed. The present study highlights the choice of DIS process and proposed optimal DIS conditions for formulating cured products. PMID- 22060946 TI - The relationship between muscularity, muscle:bone ratio and cut dimensions in male and female lamb carcasses and the measurement of muscularity using image analysis. AB - Dorsal images of 57 whole lamb carcasses (mean 22.5 kg, SD 2.3 kg) were obtained on a slaughter chain using a video camera. The lambs represented two sexes (29 cryptorchids, 28 ewes) and one genotype (Poll Dorset * Border Leicester * Merino). Cryptorchid carcasses were significantly (P < 0.05) leaner than ewe carcasses at a common weight but there was little difference in dimensional measurements of M. longissimus thoracis et lumborum (LL). The cryptorchid carcasses had a significantly better conformation (based on the EUROP system) even when adjusted to the same carcass weight and subcutaneous fat level. From the hindleg and chump the following muscles were dissected and weighed: M. semimembranosus, M. adductor femoris, M. semitendinosus, M. biceps femoris, and M. quadriceps femoris. The femur was weighed, the length measured and a muscularity value calculated as described by Purchas et al. (1991 Meat Sci., 30, 181). There was no significant effect of sex on muscularity or muscle to bone ratio (M:B). Cryptorchid carcasses produced heavier (P < 0.05) round and midloin cuts but lighter (P < 0.05) chump and ribloin cuts. Overall there was no significant sex effect on the yield of hindquarter cuts. Correlation showed a significant (P < 0.001) association between LL area and muscularity, with a lower correlation between round and topside cross-sectional area and muscularity. Neither muscle cross-sectional area nor muscularity was significantly related to M:B ratios. Muscularity increased with increasing carcass weight (P < 0.001) but M:B did not. Prediction of muscularity was significantly (P < 0.05) improved by adding to hot carcass weight a measure of the combined width across the hind legs at interval three, as taken from video images, there being five equally-spaced intervals from the groin to the gambrel. A similar result was achieved by using carcass width at the third interval of five-eventy spaced intervals between the minimum shoulder width and the point of maximum loin width. There was no significant (P > 0.05) effect of sex on the relationships. It is concluded that muscularity could be used to indicate carcasses that have cuts with greater cross sectional areas and that a video image analysis approach could potentially be used to derive an estimate of muscularity. The value to the meat marketing chain of identifying carcasses with large crosssectional areas remains to be established. PMID- 22060947 TI - Error monitoring dysfunction across the illness course of schizophrenia. AB - Response monitoring abnormalities have been reported in chronic schizophrenia patients, but it is unknown whether they predate the onset of psychosis, are present in early stages of illness, or are late-developing abnormalities associated with illness progression. Response-synchronized event-related potentials (ERP) recorded during a picture-word matching task yielded error related negativity (ERN), correct-response negativity (CRN), and error positivity (Pe) from 84 schizophrenia patients (SZ), 48 clinical high risk patients (CHR), and their age-matched healthy controls (HC; n = 110 and 88, respectively). A sub sample of 35 early illness schizophrenia patients (ESZ) was compared to 93 age matched HC and the CHR patients (after statistically removing the effects of normal aging). Relative to HC, 1) SZ, ESZ, and CHR had smaller ERNs, and 2) SZ and ESZ had larger CRNs and smaller Pes. Within the SZ, longer illness duration was associated with larger CRNs but was unrelated to ERN or Pe. CHR and ESZ did not differ on ERN or CRN, although Pe was smaller in ESZ than CHR. These results indicate that while ERN, CRN, and Pe abnormalities are present early in the illness, only the ERN abnormality is evident prior to psychosis onset, and only the CRN abnormality appears to worsen progressively over the illness course. Brain regions subserving response monitoring may be compromised early in the illness and possibly during its clinical prodrome. PMID- 22060948 TI - Deconstructing the age-prevalence curve of alcohol dependence: why "maturing out" is only a small piece of the puzzle. AB - Epidemiological studies have consistently demonstrated that heavy alcohol use and alcohol dependence (AD) tend to increase in adolescence and emerging adulthood and then show a large decline in the late 20s, a phenomenon called maturing out. This decline has been explained as an effect of "role incompatibility" in which involvement in new roles and activities interferes with a heavy drinking lifestyle. However, maturing out has been conceived mostly as a decrease in offset, with little attention paid to reductions in new onset or recurrence across decades of life. Moreover, although role incompatibility processes have been studied with young samples, little is known about the effect of life transitions (e.g., marriage, parenthood, changes in employment status) on AD later in life and whether similar effects are observed. Using longitudinal data from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative epidemiologic survey, we examined the patterns of stability and change in AD across the life span and the differential effect of life transitions on AD across different age strata. Results showed that persistence of AD tended to increase with age, although not dramatically, and that onset and recurrence tended to decrease with age. Moreover, the effects of life transitions on the course of AD varied across the life span and were different for men and women. These results indicate that life transitions differentially affect the patterns of stability and change in younger versus older people, have a different impact for men and women, and highlight the need to consider the unique aspects of each stage of adult development on the course of AD. PMID- 22060949 TI - The measurement of the responses to different odour intensities of 'boar taint' using a sensory panel and an electronic nose. AB - This study explored the possibility of using an electronic nose (e-nose) with a 12-conducting-polymer sensor array combined with pattern recognition routines to discriminate between varying intensities of boar taint. A set of samples in a model system comprising a neutral lipid base containing varying combinations of androstenone and skatole were tested, as were pork fat samples. The e-nose responses for pork fat were calibrated against those given by a trained 10-member sensory panel for abnormal odour of the same samples from a total of 60 Large White cross-bred pigs. The e-nose responses related strongly to those of the sensory panel with a significant (p<0.01) canonical correlation of 0.78. The data set was used to develop a discriminant function for grouping pork samples into three 'response classes': normal, doubtful and abnormal. Based on this, the e nose identified all the abnormal samples correctly. However, 16% of the normal samples were also classified as abnormal. It was concluded that, in general, the electronic nose can discriminate between different levels of boar taint and that although a high specificity of sensors to androstenone and skatole may be desirable it may not be entirely important to the development and configuration of a boar taint sensor array. PMID- 22060950 TI - Effect of dietary vitamin e on the oxidative stability of raw and cooked rabbit meat. AB - The effect of dietary alpha-tocopheryl acetate supplementation (200mg/kg diet) on plasma and muscle levels of alpha-tocopherol and the oxidative stability of raw and cooked rabbit meat was determined. Two groups of 20 male hybrid rabbits were fed the experimental diets from 35 to 80 days of age. Feed intake, live weight, feed efficiency and qualitative traits of the carcass and meat were recorded. The alpha-tocopherol levels in plasma and muscle were significantly higher (p<=0.01) in the supplemented group, which also showed an increase in oxidative stability in both raw and cooked meat. The higher alpha-tocopherol level improved the physical traits of the meat, significantly reducing shear value and increasing water-holding capacity; n-3 fatty acids in raw and cooked meat increased (p<=0.05) and the thrombogenic index decreased (p<=0.05). Dietary vitamin E did not influence weight gain, feed intake and dressing yield. PMID- 22060951 TI - Effects of substituting a concentrated diet for chestnuts on the lipid traits of muscle and adipose tissues in corsican and corsican * large white pigs reared in a sylvo-pastoral system in corsica. AB - In the sylvo-pastoral extensive system in Corsica, pigs are fattened with chestnuts. The decrease in chestnut resource forces the farmers to use more and more concentrated diets for feeding the pigs but so far they have disregarded the consequences of this on meat quality. The aim of the present study was to evaluate the effects of substituting a concentrated diet for chestnuts during the fattening period on the lipid composition of adipose and muscle tissues of ham in Corsican and Corsican * Large-White pigs. The results showed that the Corsican * Large-White pigs had heavier carcasses (125kg versus 106kg) and hams (12.5kg versus 10.2kg) but the genotype affected neither the carcass fatness nor the lipid composition of the adipose and muscle tissues. In addition, compared to chestnuts, the concentrated diet used did not affect live-weight, carcass and ham weights, or the carcass fatness of the pigs at slaughter. However, pigs fattened with a concentrated diet had adipose tissue lipids, intramuscular triglycerides and phospholipids with a lower proportion of polyunsaturated fatty acids (8.1% versus 6.2%, 5.8% versus 4.5%, and 47.7% versus 37.1%, respectively). PMID- 22060952 TI - Comparison of Dehiding versus Scalding and Singeing: Effect on Temperature, pH and Meat Quality in Pigs. AB - The aim of this work was to investigate the temperature and pH changes taking place at the slaughter line and during the chilling process, and the subsequent effect on meat and eating quality in pig carcasses that had either been scalded and singed or dehided. Both processes were followed by fast chilling. 219 halothane-gene-free Duroc Sire and Landrace-Yorkshire pigs were delivered from three farms and slaughtered over 2 weeks at either a dehiding or a scalding singeing slaughterhouse. Temperature and pH were measured at intervals from exsanguination until 6 hours post mortem. Ultimate pH, internal reflection, drip loss and colour (Minolta) were measured the day after slaughter. Colour (JPCS scale) was evaluated after freezing and thawing, and eating quality was estimated on unaged and aged (4 days at 4 degrees C) m. longissimus dorsi (LD), using a trained taste panel. At the slaughter line the dehided carcasses had an almost constant and lower temperature compared to the scalded and singed carcasses. During chilling there is a shift in temperature curves between treatments, where the scalded carcasses had the lowest muscle temperature in LD and m. biceps femoris (BF) from 2hr post mortem and throughout the measuring period. In spite of the shift in temperature, the dehided carcasses had the highest pH in LD and BF from exsanguination and throughout the measuring period. The rate of pH fall in LD and BF was slowest in the dehided carcasses from exsanguination until 3 and 2hr respectively, post mortem. Dehided carcasses showed a 40% lower drip loss, a darker meat colour and a lower internal reflection in LD and BF compared to scalded and singed carcasses, thus indicating less protein denaturation in dehided carcasses. Scalding and singeing, however, lead to increased tenderness compared to dehiding, and this difference persisted even after ageing for 4 days at 4 degrees C. The differences in toughness may be caused by increased proteolysis by released lysosomal cathepsins. PMID- 22060953 TI - Effect of Dietary Supplementation with alpha-Tocopheryl Acetate on the Stability of Reformed and Restructured Low Nitrite Cured Turkey Products. AB - The objective of this study was to investigate the effects of sodium (Na) nitrite reduction on the oxidative and colour stability of reformed and restructured cured cooked turkey products manufactured from meat containing high and low levels of dietary alpha-tocopheryl acetate. Turkeys were randomly assigned to either a control group, fed a basal alpha-tocopheryl acetate diet (20mg/kg feed), or a treatment group fed a supplemented alpha-tocopheryl acetate diet (600mg/kg feed). Diets were fed ad libitum from day 1 until slaughter on day 147. Breast meat from control and treatment groups was used to manufacture cured reformed cooked turkey ham and cured restructured cooked turkey patties. Residual levels of 60 and 120mg Na nitrite/kg of meat were used. Turkey products were packaged in either overwrap or vacuum packaging and stored under refrigerated (4 degrees C) illuminated display for 10 days. Results showed that dietary supplementation with alpha-tocopheryl significantly (p<0.05) improved the oxidative and colour stability of all low nitrite products produced when compared to non-supplemented controls. PMID- 22060954 TI - Effects of dietary vitamin e supplementation and packaging on the quality of minced beef. AB - Friesian cattle, aged 26-27 months, were fed a diet supplemented with 2000IU alpha-tocopheryl acetate/kg feed/day and another group was fed a basal diet (20IU/kg feed/day) for approximately 50 days prior to slaughter. Following frozen storage (-20 degrees C for 8 weeks) semimembranosus muscles from basal and alpha tocopheryl acetate supplemented cattle were minced and vacuum packaged, aerobically packaged or packaged under modified atmospheres (MAP) (30% O(2): 70% CO(2); 70% O(2): 30% CO(2); 80% O(2): 20% CO(2)). Samples were held under refrigerated (4 degrees C) display (fluorescent lighting, 616 lux) for eight days. Vacuum-packaged samples were held under similar conditions but in complete darkness and allowed to bloom for a minimum of 4hr prior to taking colour readings. TBARS values and Hunter a values in minced beef were measured every two days. alpha-Tocopherol concentrations were significantly (p<0.05) higher in minced meat samples from the supplemented group than in the basal group. Significant (p<0.05) reductions in alpha-tocopherol concentrations in supplemented meat samples were observed with increased concentrations of oxygen in different packaging systems after eight days of refrigerated storage. TBARS values were reduced over the whole retail display period for all packaging systems when alpha-tocopheryl acetate supplemented beef was used. TBARS values increased as oxygen levels increased in MAP. Hunter a values showed that vitamin E supplementation in combination with vacuum packaging and MAP improved the colour stability of meat during the first 4 days of storage, however, the failure of MAP to extend meat colour for longer periods of time was probably the result of prior storage at -20 degrees C for 8 weeks. PMID- 22060955 TI - Effects of Dietary Rape Seed Oil, Copper(II) Sulphate and Vitamin E on Drip Loss, Colour and Lipid Oxidation of Chilled Pork Chops Packed in Atmospheric Air or in a High Oxygen Atmosphere. AB - The effect of addition of rapeseed oil (canola), CuSO(4) and vitamin E (all-rac alpha-tocopheryl acetate) to pig diets on pork meat quality (lipid oxidation, colour and drip loss) was studied. Pigs were reared on ten different diets, either a control diet (no supplementation of rapeseed oil, CuSO(4) or vitamin E) or 6% rapeseed oil diets supplemented with CuSO(4) (0, 35 or 175mg/kg) and vitamin E (0, 100 or 200mg all-rac-alpha-tocopheryl acetate/kg). The natural content of vitamin E originating from feed ingredients amounted to 9-23mg vitamin E (alpha-tocopherol) per kg feed. Muscle vitamin E levels reflected the dietary intake and pigs fed the control diet had significantly lower levels than pigs fed rapeseed oil diets. The quality of fresh pork chops packed in air or in 80% O(2):20% CO(2) was followed during chill storage for 8 and 13 days, respectively. Colour, as measured by tristimulus colorimetry of pork chops packed in 80% oxygen atmosphere, was significantly improved with respect to redness when compared to chops packed in air, regardless of dietary treatment. The low vitamin E content in pigs fed the control feed significantly decreased a values and the oxidative stability of pork chops during chill storage compared to the other feeding groups. Packing of chops in a high-oxygen atmosphere increased lipid oxidation, especially in chops with low levels of vitamin E. Supplementation of rapeseed oil diets with 100 or 200mg vitamin E significantly decreased lipid oxidation of chill stored chops. Supplementation with CuSO(4) did not influence meat quality attributes (drip loss, colour stability and lipid oxidation) for any of the storage conditions. PMID- 22060956 TI - Effect of Chemical and Physical Dry-curing Parameters on Cathepsins B, H and L from Ostrich Muscle. AB - The effects of curing agents (NaCl, nitrate, ascorbic acid and glucose) and processing parameters (pH, temperature and cooking temperatures) on cathepsins B, H and L activities were investigated. NaCl, nitrate, ascorbic acid and glucose exhibited different influences on ostrich cathepsin B, B+L and H activities. In the range 20-60gl(-1), NaCl inhibited cathepsin B+L and H activities. All three cysteine proteinase activities were inhibited by up to 8g ascorbic acid l(-1). With the exception of cathepsin B activity, which was inhibited by glucose, nitrate and glucose had very little effect on cathepsin B, B+L and H activities. Cathepsins B and D were active at 65 and 69 degrees C and might play an important degradative role during the cooking of meat and meat products. Cathepsins B, B+L and H were optimally active at temperatures of 40-45 degrees C and 50 degrees C, and were still quite active at the low temperatures used in the dry-curing process; they showed maximum activity in the pH range 5.5-7. A simulation of the three stages of the dry-curing process of hams revealed that cathepsins B and B+L might play an important role throughout the complete process, whereas cathepsin H could only participate in the middle and at the end of the dry-curing process. Although ostrich cathepsins show many properties similar to those from other species, the present study also revealed some interesting distinguishing features. PMID- 22060957 TI - Effect of muscle condition before freezing and simulated chemical changes during frozen storage on protein functionality in beef. AB - The effect of rigor temperature (RT, 35 versus 10 degrees C), increased ionic concentration (MS: 0 versus 0.2% mixed salts), oxidized lipids (OL, 0 versus 1% added oxidized fat), increased free amino acids (FAA, 0 versus 0.3% added mixture of amino acids), fat content (FC, 0 versus 15% added fat) and excluding atmospheric gases (V, 0 versus 99.9% vacuum) on protein functionality in mince stored 1 month at -20 degrees C was studied using a complete 2(6) factorial design. All factors studied affected the functional properties of beef. Fresh 24hr samples that entered rigor at 35 degrees C had lower total (TPS), myofibrillar (MPS) and sarcoplasmic (SPS) protein solubilities than samples entering rigor at 10 degrees C (p<0.01). During frozen storage, RT, MS and OL alone did not affect protein solubilities, FAA increased TPS but did not affect MPS and SPS, increasing the meat's fat content raised TPS and SPS but did not affect MPS, applying a vacuum increased TPS and MPS but lowered SPS (p<0.05). Cook yield of frozen stored mince increased with higher FAA but decreased with higher fat content, and the peak force of patties made from frozen stored mince was lowered by increased MS and low FC during storage. Various significant interactions are tabulated and discussed. PMID- 22060958 TI - Effect of Muscle Condition Before Freezing and Simulated Chemical Changes During Frozen Storage on the pH and Colour of Beef. AB - The effect of rigor temperature (RT, 35 versus 10 degrees C), increased ionic concentration (MS, 0 versus 0.2% mixed salts), oxidized lipids (OL, 0 versus 1% added oxidized fat), increased free amino acids (FAA, 0 versus 0.3% added mixture of amino acids), fat content (FC, 0 versus 15% added fat) and excluding atmospheric gases (V, 0 versus 99.9% vacuum) on pH and colour of mince stored for one month at -20 degrees C was studied using a complete 2(6) factorial design. Adding FAA increased the meat pH measured after storage (p<0.001). Meat lightness (Hunter L* value) was increased by increased fat content (p<0.001), higher rigor temperature (p<0.001) and oxidized lipids (p<0.05). Vacuum packing tended to preserve redness (Hunter a*) whereas the higher rigor temperature decreased redness (p<0.001). Vacuum packing (p<0.05) and increased fat content (p<0.001) increased yellowness (Hunter b*). The hue angle was lowered by increased salt concentration (p<0.01), increased free amino acids (p<0.01) and using vacuum packing (p<0.001), whereas it was raised (p<0.001) by increased fat content and higher rigor temperature. Various significant two-and three-way interactions are tabulated and discussed. PMID- 22060959 TI - Influence of sampling on steroid hormone patterns of beef from bulls and steers. AB - Three different muscles (Longissimus dorsi, Semitendinosus, Extensor carpi ulnaris) of bulls and steers, which represent different parts of the carcass and which have differing properties (function, proportions of fat and connective tissue), were analysed with GC-MS for their contents of testosterone, cortisol, cortisone, pregnenolone, dehydroepiandrosterone, progesterone, hydroxyprogesterone, androstenedione, dihydrotestosterone, epitestosterone and androsterone. No difference in the hormone patterns could be detected between the three muscles. However, the enrichment of beef samples with inter- and intramuscular fat decreased the levels of the polar corticosteroids, whereas the levels of lipophilic steroids were increased. The patterns of the lipophilic sex steroids, their precursors and metabolites, which can be used to determine the sexual origin of beef and which might prove useful in evaluating residues of administered steroid hormones, seem to be less affected by the beef sample's fat content, however. PMID- 22060960 TI - The bacteriological quality of British beef 1. Carcasses sampled prior to chilling. AB - During a survey of 11 beef abattoirs in England 2200 swab samples were taken from carcasses just before chilling. Geometric mean aerobic plate counts at 30 degrees C on each of four carcass sites ranged from log(10) 2.45 to 4.29cfu cm(2) with the brisket and flank samples tending to be more highly contaminated than those from the fore-rib and groin. Presumptive coliforms were isolated from 24% of the samples and the proportion of positive samples among the abattoirs varied between 1.5% and 43%. Analysis of variance confirmed that the bacteriological status of beef carcasses may be influenced by a number of interacting factors, including abattoir, visit, and sampling site. However, the results showed that working methods alone were not critical factors in the production of beef of superior bacteriological quality. PMID- 22060961 TI - QTc prolongation and diabetes therapies. PMID- 22060963 TI - Evaluation of the occurrence and biodegradation of parabens and halogenated by products in wastewater by accurate-mass liquid chromatography-quadrupole-time-of flight-mass spectrometry (LC-QTOF-MS). AB - An assessment of the sewage occurrence and biodegradability of seven parabens and three halogenated derivatives of methyl paraben (MeP) is presented. Several wastewater samples were collected at three different wastewater treatment plants (WWTPs) during April and May 2010, concentrated by solid-phase extraction (SPE) and analysed by liquid chromatography-electrospray-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). The performance of the QTOF system proved to be comparable to triple-quadrupole instruments in terms of quantitative capabilities, with good linearity (R(2) > 0.99 in the 5-500 ng mL(-1) range), repeatability (RSD < 5.6%) and LODs (0.3-4.0 ng L(-1) after SPE). MeP and n propyl paraben (n-PrP) were the most frequently detected and the most abundant analytes in raw wastewater (0.3-10 MUg L(-1)), in accordance with the data displayed in the bibliography and reflecting their wider use in cosmetic formulations. Samples were also evaluated in search for potential halogenated by products of parabens, formed as a result of their reaction with residual chlorine contained in tap water. Monochloro- and dichloro-methyl paraben (ClMeP and Cl(2)MeP) were found and quantified in raw wastewater at levels between 0.01 and 0.1 MUg L(-1). Halogenated derivatives of n-PrP could not be quantified due to the lack of standards; nevertheless, the monochlorinated species (ClPrP) was identified in several samples from its accurate precursor and product ions mass/charge ratios (m/z). Removal efficiencies of parabens and MeP chlorinated by products in WWTPs exceeded 90%, with the lowest percentages corresponding to the latter species. This trend was confirmed by an activated sludge biodegradation batch test, where non-halogenated parabens had half-lives lower than 4 days, whereas halogenated derivatives of MeP turned out to be more persistent, with up to 10 days of half-life in the case of dihalogenated derivatives. A further stability test performed with raw wastewater also showed that parabens degrade rapidly in real sewage, with half-lives lower than 10 h for n-butyl-paraben, while dihalogenated species again turned out to be more stable, with half-lives longer than a week. PMID- 22060964 TI - Establishment of a real-time PCR method for quantification of geosmin-producing Streptomyces spp. in recirculating aquaculture systems. AB - Geosmin and 2-methylisoborneol (MIB) have been associated with off-flavour problems in fish and seafood products, generating a strong negative impact for aquaculture industries. Although most of the producers of geosmin and MIB have been identified as Streptomyces species or cyanobacteria, Streptomyces spp. are thought to be responsible for the synthesis of these compounds in indoor recirculating aquaculture systems (RAS). The detection of genes involved in the synthesis of geosmin and MIB can be a relevant indicator of the beginning of off flavour events in RAS. Here, we report a real-time polymerase chain reaction (qPCR) protocol targeting geoA sequences that encode a germacradienol synthase involved in geosmin synthesis. New geoA-related sequences were retrieved from eleven geosmin-producing Actinomycete strains, among them two Streptomyces strains isolated from two RAS. Combined with geoA-related sequences available in gene databases, we designed primers and standards suitable for qPCR assays targeting mainly Streptomyces geoA. Using our qPCR protocol, we succeeded in measuring the level of geoA copies in sand filter and biofilters in two RAS. This study is the first to apply qPCR assays to detect and quantify the geosmin synthesis gene (geoA) in RAS. Quantification of geoA in RAS could permit the monitoring of the level of geosmin producers prior to the occurrence of geosmin production. This information will be most valuable for fish producers to manage further development of off-flavour events. PMID- 22060965 TI - 2-fluorophenol degradation by aerobic granular sludge in a sequencing batch reactor. AB - Aerobic granular sludge is extremely promising for the treatment of effluents containing toxic compounds, and it can economically compete with conventional activated sludge systems. A laboratory scale granular sequencing batch reactor (SBR) was established and operated during 444 days for the treatment of an aqueous stream containing a toxic compound, 2-fluorophenol (2-FP), in successive phases. Initially during ca. 3 months, the SBR was intermittently fed with 0.22 mM of 2-FP added to an acetate containing medium. No biodegradation of the target compound was observed. Bioaugmentation with a specialized bacterial strain able to degrade 2-FP was subsequently performed. The reactor was thereafter continuously fed with 0.22 and 0.44 mM of 2-FP and with 5.9 mM of acetate (used as co-substrate), for 15 months. Full degradation of the compound was reached with a stoichiometric fluoride release. The 2-FP degrading strain was successfully retained by aerobic granules, as shown through the recovering of the strain from the granular sludge at the end of the experiment. Overall, the granular SBR has shown to be robust, exhibiting a high performance after bioaugmentation with the 2-FP degrading strain. This study corroborates the fact that bioaugmentation is often needed in cases where biodegradation of highly recalcitrant compounds is targeted. PMID- 22060966 TI - Charge specific protein placement at submicrometer and nanometer scale by direct modification of surface potential by electron beam. AB - The understanding and the precise control of protein adsorption is extremely important for the development and optimization of biomaterials. The challenge resides in controlling the different surface properties, such as surface chemistry, roughness, wettability, or surface charge, independently, as modification of one property generally affects the other. We demonstrate the creation of electrically modified patterns on hydroxyapatite by using scanning electron beam to tailor the spatial regulation of protein adsorption via electrostatic interactions without affecting other surface properties of the material. We show that domains, presenting modulated surface potential, can be created to precisely promote or reduce protein adsorption. PMID- 22060967 TI - Cryogenic chilling of pork carcasses: Effects on muscle quality, bacterial populations and palatability. AB - Two experiments were conducted to determine the effects of cryogenic chilling on the carcass shrinkage, meat quality, bacterial condition and palatibility of pork. In experiment I, pork sides were chilled at 1 degrees C (n = 20), or immersed in liquid nitrogen (LN) for 1 or 3 min prior to placement in a 1 degrees C cooler. Muscle temperature in the loin was significantly lower at 2 and 6 h post mortem in treated compared to control sides, and loin muscle pH was higher (P < 0.05) at 6 h post mortem in sides immersed for 3 min in LN. Carcass side shrinkage was reduced from 29.3 g kg(-1) in control sides to 20.9 and 13.5 g kg( 1) in sides dipped in LN for 1 and 3 min. Chilling treatment had no significant effect on the survival of mesophilic bacteria on carcass sides, on meat colour, drip loss, protein solubility or sarcomere length, but sides dipped for 1 min in LN has a higher muscle shear value than control sides. In experiment II, carcass sides from halothane positive (H+) and negative (H-) pigs were conventionally chilled (n = 49), immersed in LN for 3 min (n = 23), or electrically stimulated and chilled in LN for 3 min (n = 26). Similar results for temperature, pH, colour, protein solubility and drip loss in loin muscle were found to those in experiment I. Laboratory taste panel results showed that chilling treatment had no effect on palatability. Genotype produced meaningful differences in most palatability attributes with H+ pigs having less tender, less juicy and less desirable flavour than pork from H- pigs. Laboratory studies with inoculated fresh muscle slices showed that a 3 min immersion in LN resulted in a 10-fold reduction in the aerobic spoilage pseudomonads, but effects upon other spoilage bacteria and potential human pathogens were less pronounced. It was concluded that cryogenic chilling using LN reduced carcass shrinkage during cooling, but had no consistent effects on meat quality, palatability or bacterial numbers on the carcass. In contrast, genotype had a significant effect on most pork quality and palatability attributes. PMID- 22060968 TI - Meat pigment determination by a simple and non-toxic alkaline haematin method-(An alternative to the hornsey and the cyanometmyoglobin methods). AB - A method is described for the determination of total pigment content in porcine meat by conversion to haematin (ferriprotoporphyrin hydroxide), and using the non ionic detergent Triton X-100 to increase the absorptivity. The method is presented as an alternative to the well-known Hornsey and cyanometmyoglobin methods. The alkaline haematin method requires a single reagent, sodium hydroxide and the detergent Triton X-100. This combination is probably less poisonous and more stable than the reagents used in the Hornsey (1956) and the cyanometmyoglobin methods. The method presented here is also more sensitive than the alkaline haematin method presented by Lawrie (1950). Reference solutions of alkaline haematin can be prepared easily. PMID- 22060969 TI - Effects of feed withdrawal before delivery on pork quality and carcass yield. AB - A total of 270 pigs from a Yorkshire/Duroc/Landrace 3-way cross, reared under an ad libitum feed regimen, were delivered for slaughter after fasting (with access to water) for 24 and 0 h (Exp. 1), 16 and 0 h (Exp. 2) and 24, 16 and 0 h (Exp. 3). The interval between delivery and slaughter was 4-5 h. Feeding until delivery resulted in a lower pH at 45 min post mortem in the longissimus muscle. Ultimate pH values of longissimus and semimembranosus muscles were higher after feed restriction for 24 h. However, the incidence of dark, firm and dry (DFD) (pH > 6.2) was also increased after fasting in Exp. 1. Assessment of meat quality in samples taken from the longissimus at 20 h post mortem showed that, in comparison with feeding until delivery. Hunter L(*) (Lightness)-values and drip loss decreased and firmness improved by prolonged fasting (24 h). Fasting for 16 h did not reduce drip loss, but colour was improved (lower Hunter L(*)-values) in Exp. 3, although not in Exp. 2. Feeding until delivery resulted in better meat quality in Exp. 2 than in Exp. 1 and 3. A significant reduction in dressing percentage as a result of fasting was only found in Exp. 1. There appears no economic disadvantage in restricting feed for 16 h prior to delivery. Although the incidence of DFD may also increase, a fasting period of 16-24 h is recommended to reduce pale, soft and exudative (PSE) muscle, while losses in carcass yield are minimized. Other advantages of fasting are discussed. PMID- 22060970 TI - Carcass composition and meat quality of Chinese purebred and European * Chinese crossbred pigs. AB - Carcass composition and meat quality were compared in Chinese purebred native pigs (Meishan and Ming) and the same breeds crossed with Landrace. Duroc * Landrace were controls. The study was part of a programme to improve pig production in Japan by introducing Chinese native pigs. The loin meat from Chinese purebred pigs received higher sensory scores than that from crosses between Landrace and Duroc (abbreviated as LD). Separable fat percentage of the carcass from Chinese purebred pigs was about 2.5 times higher than that from LD pig. This separable fat was decreased by crossbreeding with Landrace. Water holding capacity (WHC) of the meat from Chinese purebred and crossbred pigs was slightly higher than that from LD. Significant difference in the contents of amino acids and peptides was not observed among the species examined. Contents of inosinic acid (IMP), one of the flavour components, in the meat from Chinese purebred and crossbred pigs were higher than that from LD. From histochemical observation, an unusual distribution of fat in the muscle fibre was observed in the muscle from Chinese purebred pigs, especially Ming, as compared with other species. PMID- 22060971 TI - Endurance-exercised growing sheep: I. Post-mortem and histological changes in skeletal muscles. AB - A study was conducted with Suffolk ram lambs to determine whether chronic endurance exercise would affect post-mortem changes in muscle tissue. Muscle fibre diameters, sarcomere lengths, fibre types, and pH and temperature declines were measured in five skeletal muscles (semimembranosus, SM: vastus lateralis, VL; semitendinosus, ST; psoas major, PM; gastrocnemius, G). The exercise had no significant effect on muscle size or muscle fibre diameter in any of the muscles studied. However, endurance-exercised sheep had significantly shorter sarcomeres in all five muscles than their non-exercised counterparts. The pH decline curves differed among muscles; those having the highest proportion of glycolytic fibres had the slowest rates of pH decline. The increased proportion of slow-twitch fibres in the SM, VL, ST and G associated with the exercise regime had little effect on the post-mortem pH decline. However, the ST also had a significant exercise-associated increase in the proportion of oxidative-glycolytic fibres (intermediate) and was the only muscle in which exercise influenced the rate of pH decline significantly. PMID- 22060972 TI - Endurance-exercised growing sheep: II. Tenderness increase and change in meat quality. AB - A study was conducted to examine the effect, in ram lambs, of chronic treadmill exercise, on meat quality. A secondary objective was to relate changes in tenderness to metabolic and chemical phonomena. Meat quality traits, including instrumental measurements of tenderness and thaw and drip losses, were recorded for two muscles from the hind limb (semimembranosus SM; vastus lateralis, VL). Chemical analyses, including total and soluble collagen, total and myofibrillar protein, and myofibrillar fragmentation were also performed. Muscles from exercised sheep were significantly more tender than muscles from their control counterparts. A larger myofibrillar protein to total collagen ratio was observed in the VL muscles from exercised sheep (P < 0.01) which probably contributed to the observed increase in tenderness. However, similar results were not observed for the SM muscle. The tendency for a slightly higher pH at similar post-mortem temperatures in meat from exercised sheep may also have contributed to the increased tenderness. PMID- 22060973 TI - Effect of reduced sodium chloride concentration and tetrasodium pyrophosphate on pH, water-holding capacity and extractable protein of prerigor and postrigor ground beef. AB - The effect of tetrasodium pyrophosphate (TSPP) (0, 0.25, 0.5% w/w) alone or in combination with salt (NaCl) (0, 0.5, 1.0% w/w) on water-holding capacity (WHC), pH, the ratio of absorbance at 250 nm over the absorbance at 260 nm (R-values) and 150m CaCl extractable protein (EP) was studied in prerigor and postrigor sternomandibularis homogenates over time. The 0 h samples were defined as when the NaCl was incorporated with the muscle. R-values verified that 0 h samples were in a prerigor or postrigor state. In prerigor homogenates, increasing phosphate concentration increased the time required to reach ultimate pH. Ultimate pH values of prerigor homogenates containing phosphate were lower (P < 0.05) than homogenates without phosphate and similarly treated postrigor homogenates. After six hours, no differences (P > 0.10) were noted in EP or WHC at different phosphate concentrations when averaged over NaCl concentrations in prerigor homogenates. With increasing phosphate concentration of postrigor homogenates, there was an increase (P < 0.05) in pH and EP at the initial sampling time. However, 0 and 0.25% phosphate WHC values could not be differentiated (P > 0.10). Results of this study indicate no advantages, after six hours post mortem, to using TSPP alone or in combination with NaCl in prerigor meat homogenates at concentrations added in this study. PMID- 22060975 TI - Dr nirihide ando (1909-1990). PMID- 22060974 TI - Quality control in the meat industry by multivariate statistics. The case of raw ham. AB - Two multivariate statistical techniques were tested on sensory and instrumental data from raw ham technology. (1) Cluster analysis, applied to parameters ranging from the beginning of processing to the end of resting, originated three groups which provided an explanation of the observed trends in the occurrence of microbial defects. (2) Partial-least-squares (PLS) regression, used to relate three sensory descriptors to five instrumental variables, provided a fully instrumental method for the assessment of quality of aged ham. Application of both techniques for prediction and description purposes is discussed. PMID- 22060976 TI - Developing the skill of endotracheal intubation: implication for emergency medicine. AB - BACKGROUND: Securing the airway by means of endotracheal intubation (ETI) represents a fundamental skill for anaesthesiologists in emergency situations. This study aimed to evaluate the time needed by first-year anaesthesiology residents to perform 200 ETIs and assessed the associated success rates and number of attempts until successful ETI. METHODS: This prospective single centre study evaluated the number of working days, the success rate, the attempts needed until successful ETI in consecutive blocks of 25 ETI procedures and the related difficulties and complications. RESULTS: From 2007 to 2010, 21 residents were evaluated consecutively. These residents needed a mean (mean +/- standard deviation) of 15.6 +/- 3.0 days for 25 ETIs. Out of all residents 52% reached the target value of 200 ETIs after 50.2 +/- 14.8 weeks of total working time. The ETI success rate after the first 25 ETIs increased steadily to the results after 200 ETIs (ETI success rate within one ETI attempt: 67% vs. 83%, P = 0.0001; ETI success rate within all ETI attempts: 82% vs. 92%, P = 0.0001). The number of attempts required until successful ETI decreased from 1.6 +/- 0.8 after the first 25 ETIs to 1.3 +/- 0.6 after 200 ETIs (P = 0.0001). CONCLUSION: The increasing rate of relative ETI success and the decreasing rate of necessary attempts for successful airway management suggest a steadily increasing gain in ETI experience. The complications that developed during the first 200 ETI procedures justify supervision by a specialist in the field or a senior physician. Moreover, these results may influence the minimum requirement for qualification in anaesthesiology and emergency medicine. PMID- 22060977 TI - Positive Darwinian selection in gamete recognition proteins of Strongylocentrotus sea urchins. AB - Gamete recognition proteins commonly experience positive Darwinian selection and evolve more rapidly than nonreproductive proteins, but the selective forces responsible for their adaptive diversification remain unclear. We examined the patterns of positive selection in the cognate interacting pair of proteins formed by sperm bindin and its egg receptor (EBR1) and in two regions of the sea urchin sperm receptor for egg jelly suREJ3 gene (exons 22 and 26) among four species of Strongylocentrotus sea urchins (S. purpuratus, S. droebachiensis, S. pallidus and S. franciscanus). The signatures of selection differed at each reproductive protein. A strong signal of positive selection was detected at bindin in all lineages even though the species compared had highly variable gamete traits and experience different intensities and forms of sexual selection and sexual conflict in nature. Weaker selection was observed at EBR1 but the small region studied precluded a clear understanding of the extent of sexual conflict between bindin and the EBR1 protein. At the suREJ3 locus, diversifying selection was observed in exon 22 but not exon 26, suggesting that these regions experience different selective pressures and evolutionary constraints. Positive selection was also detected within S. pallidus at suREJ-22 because of the presence of 12 amino acid replacement mutations segregating at frequencies >0.10. Our results suggest that sexual conflict may be the predominant evolutionary mechanism driving the rapid diversification of reproductive proteins between, and polymorphism within, strongylocentrotid sea urchins. PMID- 22060978 TI - [Not Available]. PMID- 22060979 TI - Influence of ewe feeding systems on fatty acid composition of suckling lambs. AB - The main objective of this study was to evaluate the effects of ewe dietary treatments on the intramuscular fatty acid composition of suckling lambs. Twenty four pregnant Italian Merino ewes were divided into two equal groups. One group (pasture-fed group) was allowed to graze a natural pasture and the other group (stall-fed group) was penned indoors and fed with hay and concentrate. After lambing, all ewes stayed with their respective lambs for the whole experimental period. Lambs were slaughtered at 100 days of age with an average live weight of 20kg. Fatty acid profiles of milk and lamb meat (longissimus lumborum muscle) were analysed. Intramuscular fat from pasture-fed lambs showed higher (P<0.001) proportions of polyunsaturated fatty acids. The percentage of lauric (C12:0; P<0.05), palmitic (C16.0; P<0.001) and oleic (C18.1; P<0.001) fatty acids were higher in the intramuscular fat from stall-fed lambs, whereas pasture-fed lambs showed greater proportions of linolenic (C18:3; P<0.001), eicosapentaenoic (C20:5; P<0.001) and docosapentaenoic (C22:5; P<0.05) fatty acids. Moreover, the intramuscular fat from pasture-fed lambs displayed a higher (P<0.001) PUFA/SFA ratio, and a lower (p<0.001) n-6/n-3 ratio. The conjugated linoleic acid (CLA) tended to be higher (P=0.07) in the intramuscular fat from pasture-fed lambs. This study confirmed that pasture enhanced the unsaturated fatty acid profile of intramuscular fat in lambs including n-3 fatty acids. PMID- 22060980 TI - Carcass traits of Kheri lambs maintained on different system of feeding management. AB - The study was conducted on 6-month-old finisher lambs of the Kheri breed raised under extensive range management (G1), grazing with ad libitum concentrate supplementation (G2) or intensive feeding (G3) to assess dressing yield, cutability of standard cuts, composition of the carcass and the efficiency of mutton production from the three defined systems. The weaning weight of the lambs in the three groups was similar while the finishing weight, total body weight gain in the experiment, average daily gain and the percent feed conversion efficiency were higher (P<0.01) in G2 and G3 than G1. The pre slaughter weight (PSW), empty live weight (ELW), hot carcass weight and hot carcass weight with edible offal was higher (P<0.01) in G2 and G3 fed on a high plane of nutrition than G1 raised under extensive range management. The dressing percent in terms of live weight (LW) and empty live weight (ELW) was also higher in G2 and G3 than G1. The loin eye area as an index of muscle growth was also higher in G2 and G3 than G1. Although the weights of standard cuts were generally higher in G2 and G3 due to higher PSW, as proportions of half carcass they were similar in the three groups, except the rack cut, which was higher in G2 and G3. The cut proportions pooled for the three groups averaged 33.2%, 12.3%, 13.3%, 24.9% and 16.3% of half carcass for leg, loin, rack, neck and shoulder and breast and fore shank, respectively. The depot fat (Caul and kidney fat) accretion was higher in G2 and G3 than G1. The composition of the half carcass indicated that lean percent was higher (P<0.01) in G1 and G2 than G3 while sub cutaneous and intra muscular fat content were generally higher (P<0.01) in G2 and G3 and KOH bone percent was higher (P<0.05) in G1 and G2 than G3. The results indicated that the growth performance was better, feed conversion efficiency, carcass yield and dressing percentage higher in lambs maintained under grazing with supplementation and intensive feeding than extensive range management. The carcass separable fat content was 8% under extensive range management while it was 12% and 16% in semi intensive and intensive system of feeding management indicating that the carcass was of acceptable quality. The loin eye area reflected the trends of pre slaughter weight and was higher in intensive and semi intensive than extensive range management. PMID- 22060981 TI - Demineralization of animal blood plasma by ion exchange and ultrafiltration. AB - The blood waste from slaughterhouses is strictly controlled due to its high pollutant load, the treatment for its purification being of great economic interest. The separation of proteins, the most valuable components of blood, in a chromatographic column requires the use of well treated plasma, in particular the removal of inorganic salts. Accordingly, a demineralization process is usually required. In this paper, ion exchange and ultrafiltration demineralization techniques were tested and the results compared. In the ion exchange experiments, the blood plasma was treated with cationic and anionic resins in packed columns, studying the removal of the major cations and anions, protein loss and pH evolution in both the loading and elution steps. In the demineralization process by means of membranes, a 10KDa ultrafiltration membrane was used, the blood plasma being filtered to concentrate all the proteins in the retentate while removing the inorganic ions and other compounds in the permeate. The evolution of the major anions and cations in the plasma and the protein loss were studied at different volumetric concentration factors. The results obtained enable us to draw conclusions as regards the advantages and disadvantages of each technique at a laboratory scale and to offer some considerations regarding the operation at an industrial scale. PMID- 22060982 TI - Effect of duration of feeding under free-range conditions on production results and carcass and fat quality in Iberian pigs. AB - This experiment was undertaken to provide information on the effect of feeding system applied during the finishing period (100-150kg) on the quality of Iberian pig meat. Four feeding systems were applied: pigs fed under free-range conditions with acorns and grass fully available during 111 days (FR(111)), pigs fed concentrate diet in confinement during 28 days and free-range with acorns and grass fully available during 83 days (CDC(28)+FR(83)), pigs fed concentrate diet in confinement during 65 days and free-range with acorns and grass fully available during 46 days (CDC(65)+FR(46)) and pigs fed concentrate diet in confinement with a feed average daily amount of 3.1kg during 111 days (CDC(111)). The CDC(111) pigs had more muscular carcasses characteristics than the remaining groups of pigs. However, the higher concentration of C18:1 n-9 in subcutaneous backfat was found in FR(111) pigs. In the neutral lipids from intramuscular fat of Longissimus dorsi only the C18:2 n-6 and C18:3 n-3 proportions were affected by feeding system, and the n-6/n-3 ratio observed was lower in FR(111) and CDC(28)+FR(83) pigs than in CDC(111) pigs. In the neutral lipids from hepatic fat the proportion of n-6 fatty acids was lower in FR(111) pigs than in CDC(65)+FR(46) and CDC(111) pigs. PMID- 22060983 TI - Indoor fattening of lambs raised on pasture: 2. Influence of stall finishing duration on triglyceride and phospholipid fatty acids in the longissimus thoracis muscle. AB - Twenty-four male Ile-de-France lambs (six blocks of homologous lambs) were used to study the effect of four feeding systems on muscle triglyceride (TG) and phospholipid (PL) fatty acids (FA) from the longissimus thoracis (LT): raised and finished on cool season grasses (G), raised on the same grasses and stall finished, indoors, on concentrates and hay, respectively, for 22 (GSS) and 41 days (GSL), and stall-feeding, indoors, on concentrate and hay during both growing and finishing periods (S). In TG, similar decreases (P<0.05) of proportions of linolenic acid were observed after changing from grass feeding to stall feeding (GSS and GSL), and a decrease (P<0.05) in proportions of conjugated C18:2 cis9, trans11 (CLA cis9, trans11) was obtained after a long period of concentrate feeding (GSL). In PL, C22:5 n-3 achieved a significantly (P<0.05) lower level in GSL lambs compared both G and S lambs. A similar non-significant tendency was observed in the case of the other very long chain n-3 polyunsaturated FA. The separate analysis of fatty acids of TG and PL from the LT muscle underlined that TG afforded a more significant lowering effect than PL on the overall ratio between C18:2 n-6 and C18:2 n-3 in muscle lipids and on the health potential of meat for the consumer. A PCA analysis combining FA composition of TG and PL, and growth performances of the lambs allowed an efficient discrimination between the four feeding systems. PMID- 22060984 TI - Effects of triticale-based diets on finishing pig performance and pork quality in deep-bedded hoop barns. AB - Effects of triticale diets on pig performance and pork quality were evaluated in summer and winter. Diets were: corn-soy, 40% triticale, or 80% triticale. Pigs (72kg) were fed 49d. Loins were evaluated for meat and fat quality and sensory evaluation. Average daily gain decreased as triticale inclusion increased (P<0.01). Feed intake was similar. Pigs fed corn-soy had the greatest and those fed 80% triticale had least gain:feed ratio (P<0.05). In summer, pigs fed corn soy had largest and those fed 80% triticale diet had smallest loin muscle area (P<0.05) based on ultrasound scan. During summer, ultimate pH was higher (P?0.001) and, loin purge and shear force were lower (P<0.05). Diet did not affect sensory evaluation or fatty acid profile of loins. During summer, total MUFA were more and total PUFA were less (P?0.01). Triticale fed to pigs in hoop barns slightly decreased growth without compromising pork quality. PMID- 22060985 TI - Characterization of beef semimembranosus and adductor muscles from US and Mexican origin. AB - The purpose of this study was to compare the chemical composition and sensory characteristics of two beef muscles (semimembranosus, SM and adductor, AD) from the inside round of Mexican and US origins. Inside rounds were obtained from 20 Mexican bull carcasses, representing beef of Mexican origin. Forty-vacuum packaged USDA Choice and Select inside rounds were purchased from a local trader, representing US beef. Muscles were analyzed for chemical composition, Warner Bratzler shear force (WBSF), cooking loss percentage, instrumental color, textural profile, and consumer acceptability. Muscles imported from the US contained more intramuscular fat, had higher cooking loss percentages, lower shear force values, and higher consumer ratings for overall desirability than Mexican counterparts (P<0.05). Choice and Select beef samples had similar WBSF values (P>0.05). Consumers found differences in juiciness and tenderness ratings between the two muscles, with the SM being tougher and less juicy than the AD (P<0.05). PMID- 22060986 TI - Fatty acid composition and sensory traits of beef fed palm oil supplements. AB - This study measured the effect of replacing dietary fat from an animal source with palm oil supplements on the intramuscular fatty acid profile and sensory quality traits of the meat from young bulls. Thirty-six entire male Friesian calves (mean age=6.8+/-1.1 months, mean live weight=162.5+/-28.6kg) were assigned to one of four isoenergetic (1.03 MFU/kg DM) and isoproteinic (15.5% CP) diets, that differed in their fat additives: (D1) lard-tallow mix (control); (D2) hydrogenated palm oil fatty acids (PFA); (D3) calcium salt of partially hydrogenated PFA, and (D4) calcium salt of the fatty acid distillate from palm oil. Bulls (mean live weight=391.3+/-30.3kg) were slaughtered under commercial conditions and sensory tests were performed to evaluate the effects of the four diets and ageing time (1, 10, and 21d). Only the proportions of C16:0 and C18:0 were significantly affected by the palm oil dietary supplement. Ageing time affected grass odour, tenderness, juiciness, fibrosity, liver flavour, and acid flavour. Nevertheless, palm oil supplements did not negatively alter the organoleptic characteristics of the meat. PMID- 22060987 TI - Differentiation in improvements of gel strength in chicken and beef sausages induced by transglutaminase. AB - This research investigated the improvement in the texture of chicken and beef sausages induced by using microbial transglutaminase (MTG). The epsilon-(gamma glutamyl)lysine (G-L) content and the extractability of myofibrillar proteins from these sausages were also investigated. Treatment with MTG significantly affected the breaking strength score in both meat types, especially for beef cooked at 80 degrees C (p<0.001). The protein concentration of both meat types treated with MTG and extracted in water-soluble protein solution (WSP) was slightly decreased; compared with a significant decrease (p<0.003) in samples extracted in Guba-Straub-ATP solution (GS-ATP). The variation in protein extractability of both meat types could lead to some considerations of the mechanisms and the high affinity reaction between MTG and myosin heavy chain (MHC). SDS-PAGE analysis revealed significant changes in the density of the bands after adding MTG, especially for the beef samples. The G-L content in the presence of MTG was double that in control samples of both meat types. The amount of crosslinking in chicken and beef meat was different and found to be reasonable. Collectively, this suggests that the binding ability of myofibrillar proteins with MTG is strong and dominated by MHC. There was a unique reaction among MHC proteins with MTG molecules considered as a very advantageous reaction. This leads us to suggest that the functional properties of MTG make it a beneficial protein-binding agent, positively helping the functionality of proteins to improve the texture and gelation of meat products that are treated mechanically, such as sausages. Some variation in gel improvement level between chicken and beef sausages was observed; this resulted from the variation in meat proteins in response to MTG, as well as to the original glutamyl and lysine contents. PMID- 22060988 TI - Effect of whey protein concentrate and sodium chloride addition plus tumbling procedures on technological parameters, physical properties and visual appearance of sous vide cooked beef. AB - Beef muscles cooked by the sous vide system were evaluated for the effects of pre injection tumbling, brine addition and post-injection tumbling on technological parameters, physical properties, visual appearance and tissue microstructure. The muscles were injected at 120% (over original weight) with a brine formulated to give a concentration of 3.5% whey protein concentrate and 0.7% sodium chloride on an injected raw product basis. Pre-injection tumbling did not affect most of the evaluated parameters. Brine addition reduced significantly the cooking and total weight losses. Total weight loss was 7.2% for injected muscles, and significantly higher (28.2%) for non-injected ones. Brine incorporation increased pH and reduced shear force values of cooked muscles. Extended post-injection tumbling (5rpm-10h) improved brine distribution and visual appearance, and also diminished the shear force values of cooked muscles. However, this treatment increased the weight losses of post-injection tumbling and cooking-pasteurization stages. PMID- 22060989 TI - Thermal stability of connective tissue from porcine muscles. AB - Connective tissue of three porcine muscles (M. infraspinatus, IS; M. longissimus dorsi, LD; M. semimembranosus, SM) from 27 animals [populations A (n=13, reared in Ireland) and B (n=14, reared in Finland)] was studied by measuring the collagen content, collagen solubility and thermal shrinkage temperature of the connective tissue. Colour and pH were also determined. Collagen solubility was highest in IS (p<0.05) and lowest in SM (p<0.05) although no difference between LD and SM was found in population B. The onset and peak temperatures of thermal shrinkage (T(o) and T(p)) were highest in IS (p<0.05). The lowest T(o) and T(p) were found in SM from population B whereas no differences were seen between LD and SM muscles in population A. It was concluded that the thermal stability of the connective tissue in the three porcine muscles differ. IS, as a dark muscle has high thermal shrinkage temperatures and high collagen solubilities in comparison to the lighter LD and SM muscles which have lower thermal shrinkage temperatures and collagen solubilities. Collagen contents were highest in IS and lowest in LD. PMID- 22060990 TI - Purification and partial characterisation of a matrix metalloproteinase from ostrich skeletal muscle, and its activity during meat maturation. AB - The matrix metalloproteinases (MMPs) are a homologous family of zinc proteinases that are collectively capable of catabolising the various macromolecular components of the extracellular matrix including collagens. In this study an MMP was successfully isolated and purified from ostrich skeletal muscle using Toyopearl Super Q-650S, hydroxylapatite and zinc-chelate chromatographies. The purified molecule had a molecular weight of 55K and a total of 467 amino acid residues. Purified ostrich MMP showed a pH optimum of 7 and a temperature optimum of 45 degrees C. The activity of purified ostrich MMP was shown to be inhibited by metal chelators (1,10 phenanthroline and EDTA) and partially inhibited by soy bean trypsin inhibitor. All the functional properties of ostrich MMP were compared to previously reported values for MMPs from other sources. The MMP activities in ostrich meat during a 21-day ageing period were determined and an overall increase in MMP activities was observed. PMID- 22060991 TI - Evaluation of a commercial lateral flow feed test for rapid detection of beef and sheep content in raw and cooked meats. AB - Meat species adulteration is a common problem in the retail market. This study investigated the feasibility of a commercial lateral flow immunoassay designed to detect ruminant muscle tissue in feedstuffs, such as "meat-and-bone meal" (MBM) for detection of beef and/or sheep flesh in meat mixtures, and developed a simple method for meat sample extraction. Laboratory adulterated samples including raw, cooked (100 degrees C, 30min), and sterilized (121 degrees C, 15min) beef-in chicken, beef-in-turkey, and lamb-in-pork at 0 to 1.00% (w/w) adulteration levels were extracted by different solvents (tap water, NaCl, and PB-NaCl with and without EDTA; and a kit-provided "Extraction Solvent") using three mixing methods. The test rapidly (20min) detected 0.50% (w/w) bovine or ovine meat; Extraction Solvent was the most efficient extractant tested; EDTA coupled with heating (100 degrees C, 10min) improved the assay sensitivity; and all the mixing methods achieved the same results. This immunoassay can be conveniently applied to detect low levels of beef/sheep meat in a wide range of meat products. PMID- 22060992 TI - Influence of dietary selenium and vitamin E on quality of veal. AB - Three groups of six calves each were fed a milk replacer and a starter concentrate for 15weeks. Calves of the first group received the basal diet containing selenium (Se) and vitamin E at 0.095-0.128mg and 30-33mg per kg of total solids, respectively. Calves of the second group received the basal diet supplemented with Se-enriched yeast to increase dietary Se concentration to 0.50mg/kg. The third group of calves received the latter diet supplemented with vitamin E to increase its concentration to 100mg/kg. There was no effect of diet on growth rate, digestibility of dry matter and Se, chemical composition of meat (M. Longissimus thoracis et lumborum), meat colour and fatty acid profile of meat lipids. The Se supplementation significantly increased Se concentration in muscle from 0.21 to 0.43mg/kg. The activity of glutathione peroxidase (GSH-Px) in muscle and liver tissue of Se-supplemented animals was increased by 56% and 67%, respectively, compared to the control. The combined supplementation of vitamin E and Se significantly improved the lipid stability of meat compared to the control diet, but not compared to the Se-supplemented diet. It can be concluded that dietary Se supplementation increases the concentration of Se and the GSH-Px activity in meat, but has limited potential for improving meat oxidative stability. PMID- 22060993 TI - Effect of tomato paste and nitrite level on processing and quality characteristics of frankfurters. AB - Fourteen treatments of frankfurters (18% fat) were produced with two levels of sodium nitrite, 0 and 150mg/kg (0.015%), and seven levels (0%,2%,6%,8%,12% and 16%) of tomato paste with 12% soluble solids The higher the tomato paste level the higher the preference of consumers for frankfurters based on their colour. Frankfurters with 16% tomato paste had a sour taste while those with 12% tomato paste were the most acceptable. In a 2nd experiment three treatments of frankfurters (18% fat) were produced with 0, 50 and 100mg/kg of sodium nitrite and 12% tomato paste and a fourth (control) with only 150mg/kg sodium nitrite. Treatments with 12% tomato paste had lower (p<0.05) pH values and residual nitrite, and higher (p<0.05) thiobarbituric acid values, lightness and yellowness than control. Frankfurters with reduced levels of sodium nitrite (50 and 100mg/kg) and 12% tomato paste had the highest (p<0.05) redness. Storage time affected (p<0.05) all quality attributes. The nitrites added to frankfurters can be reduced from 150mg/kg to 100mg/kg in combination with 12% tomato paste without any negative effect on the quality of the product. PMID- 22060994 TI - Prediction of sensory characteristics of lamb meat samples by near infrared reflectance spectroscopy. AB - This study was implemented to evaluate the potential of visible and near infrared reflectance (NIR) spectroscopy to predict sensory characteristics related to the eating quality of lamb meat samples. A total of 232 muscle samples from Texel and Scottish Blackface lambs was analyzed by chemical procedures and scored by assessors in a taste panel (TP). Then, these parameters were predicted from Vis/NIR spectra. The prediction equations showed that the absorbance data could explain a significant but relatively low proportion of the variability (R(2)<0.40) in the taste panel traits (texture, juiciness, flavour, abnormal flavour and overall liking) of the lamb meat samples. However, a top-tail approach, looking at the spectra of the 25 best and worst samples as judged by TP assessors, provided more meaningful results. This approach suggests that the assessors and the spectrophotometer were able to discriminate between the most extreme samples. This may have practical implications for sorting meat into a high quality class, which could be branded, into a low quality class sold for a lower price for less demanding food use. Regarding the chemical parameters, both intramuscular fat and water could be more accurately predicted by Vis/NIR spectra (R(2)=0.841 and 0.674, respectively) than sensory characteristics. In addition, the results obtained in the present study suggest that the more important regions of the spectra to estimate the sensory characteristics are related to the absorbance of these two chemical components in meat samples. PMID- 22060995 TI - Growth performance and fatty acid profiles of intramuscular and subcutaneous fat from Limousin and Charolais heifers fed extruded linseed. AB - Forty-eight heifers, Limousin (LI) and Charolais (CH) breed, were used to evaluate the effect of a basal mixed diet with linseed supplementation (108g/kg DM) on performance and fatty acid (FA) composition of M. longissimus thoracis (MLT) and subcutaneous fat. The feed intake and weight gains were higher, and feed per gain ratio lower in CH heifers than in LI heifers. The muscle lipids and subcutaneous fat of LI heifers contained significantly more MUFA, PUFA, CLA, and less SFA than the lipids of CH heifers. The feeding of extruded linseed significantly increased the concentration of linolenic acid (C18:3n-3), CLA, and decreased PUFA n-6 to PUFA n-3 ratio in lipids extracted from both tissues. Linseed supplementation decreased SFA and increased PUFA in subcutaneous fat. In MLT lipids of linseed-fed heifers PUFA of the n-3 series were increased. It can be concluded that the growth performance of LI heifers was lower, but that their lipids contained more FA that are thought to be important for human health. The feeding of linseed at 108g/kg DM enhanced the nutritive value of beef in terms of FA profile. Breed differences were generally more important than effects of the diet. Dietary effects, however, were more pronounced in PUFA n-3 and arachidonic acid (C20:4n-6). PMID- 22060996 TI - Pelvic suspension and fast post-mortem chilling: Effects on technological and sensory quality of pork - A combined NMR and sensory study. AB - The effects of pre-rigor excision, which results in a fast post-mortem chilling; pelvic suspension, which results in a muscular stretching; control treatment of m. longissimus dorsi on water distribution measured by (1)H NMR relaxometry and on sensory properties were investigated in two sub-studies including a total of 16 pigs. Determination of sarcomere length revealed significant effects of the treatments on the degree of contraction, as pre-rigor excision and pelvic suspension resulted in shorter and longer sarcomere length, respectively. In addition, an effect of treatment on pH measured at 24h post-mortem was found, as pre-rigor excision was associated with a higher ultimate pH. NMR measurements revealed that water distribution in the meat was affected to a minor degree by the various treatments. However, an interaction between treatment and ageing period was observed, as the data demonstrated an effect of pre-rigor excision on water distribution in the cooked samples when meat was only aged for 2 days, but this effect was eliminated when meat was aged for 5 days. The effect of pre-rigor excision on water distribution in cooked meat after 2 days of ageing is suggested to reflect structural constraints in the meat that are eliminated during ageing. Sensory analyses demonstrated strong interactions between treatment and position on the muscle and between treatment and ageing period. However, in general pre rigor-excised meat was sensed as significantly juicier compared with the other two treatments. Accordingly, the study demonstrates that under the present conditions the ultimate pH is more important for juiciness than the sarcomere length. PMID- 22060997 TI - Instrumental evaluation of defective texture in dry-cured hams. AB - In the first experiment, the effect of the stress relaxation time on texture evaluation of biceps femoris (BF) muscle from dry-cured hams was studied. The specimens were compressed to 25% of their original height and the crosshead speed was 5mm/s. The force decay versus time was recorded and Peleg's model was fitted with different relaxation times. Whatever relaxation time was used, Peleg's model did not describe simultaneously the initial fall of force and the asymptotic tendency of force decay correctly. The initial force and force decay at 2s and at 90s are proposed to assess texture in dry-cured ham. In the second experiment, stress relaxation (SR) and texture profile analysis (TPA) tests were performed on BF and semimembranosus (SM) muscles of 10 hams with abnormal softness and 10 hams with normal texture, at different assay conditions: sample temperature (4 degrees C or 20 degrees C); compression crosshead speed (1mm/s or 10mm/s). The instrumental texture test and the assay conditions that detected defective textures better depended on the muscle considered: for BF muscle the SR test at 4 degrees C and at 1mm/s and for SM muscle the TPA test at 10mm/s at both 4 degrees C or 20 degrees C. PMID- 22060998 TI - Use of a fluorescence front face technique for measurement of lipid oxidation during refrigerated storage of chicken meat. AB - Lipid oxidation in chicken breast was measured during refrigerated storage in air by front face fluorescence and by thiobarbituric acid techniques. Three chicken genotypes were compared: Standard (fast-growing line), Certified (medium-growing line) and Label (slow-growing line). Lipid oxidation was stable during the first 3 days of storage and then increased in the certified and label animal groups. Standard animals were very stable towards lipid oxidation. This study showed a good correlation between fluorescence intensity and thiobarbituric acid reactive substances measurements. Front face fluorescence technique can be used as a valuable index of lipid oxidation in chicken meat. PMID- 22060999 TI - Effects of hydrocolloid addition and high pressure processing on the rheological properties and microstructure of a commercial ostrich meat product "Yor" (Thai sausage). AB - "Yor" is a traditional sausage like product widely consumed in Thailand. Its textures are usually set by steaming, in this experiment ultra-high pressure was used to modify the product. Three types of hydrocolloid; carboxymethylcellulose (CMC), locust bean gum (LBG) and xanthan gum, were added to minced ostrich meat batter at concentration of 0-1% and subjected to high pressure 600MPa, 50 degrees C, 40min. The treated samples were analysed for storage (G') and loss (G") moduli by dynamic oscillatory testing as well as creep compliance for control stress measurement. Their microstructures using confocal microscopy were also examined. Hydrocolloid addition caused a significant (P<0.05) decrease in both the G' and G" moduli. However the loss tangent of all samples remained unchanged. Addition of hydrocolloids led to decreases in the gel network formation but appears to function as surfactant materials during the initial mixing stage as shown by the microstructure. Confocal microscopy suggested that the size of the fat droplets decreased with gum addition. The fat droplets were smallest on the addition of xanthan gum and increased in the order CMC, LBG and no added gum, respectively. Creep parameters of ostrich yors with four levels of xanthan gum addition (0.50%, 0.75%, 1.00% and 1.25%) showed an increase in the instantaneous compliance (J(0)), the retarded compliance (J(1)) and retardation time (lambda(1)) but a decrease in the viscosity (eta(0)) with increasing levels of addition. The results also suggested that the larger deformations used during creep testing might be more helpful in assessing the mechanical properties of the product than the small deformations used in oscillatory rheology. PMID- 22061000 TI - Combination effects of ultra-high pressure and temperature on the physical and thermal properties of ostrich meat sausage (yor). AB - Ostrich meat sausages (yor) were subjected to ultra-high pressures of 300, 500 and 700MPa for 40 and 60min at 40 and 60 degrees C. Subsequently the physical properties of the products, colour, released and expressible water, gel strength and stress relaxation as well as their thermal characteristics (by differential scanning calorimeter, DSC) were determined. The effects of pressure, temperature and holding time significantly influenced the L(*), a(*) and b(*) values. The amount of released plus expressible water significantly decreased with increasing pressure, temperature and holding time. The gel strength and equilibrium stress increased with increasing severity of treatment. DSC thermograms indicated that pressures of 700MPa yielded gel networks involving completely denatured protein with the ability to retain water. PMID- 22061001 TI - Monitoring the ripening process of Iberian ham by computer vision on magnetic resonance imaging. AB - This paper explores the use of MRI (Magnetic Resonance Imaging) in combination with a fully automated Image Analysis method for the recognition of Biceps Femoris and Semimembranosus muscles in Iberian ham. A quantitative description of volume and a study of moisture and weight relationships during the product's ripening process are included. Three Active Contour methods (Variational Calculus, Dynamic Programming, and Greedy Algorithms) are used to recognize the Biceps Femoris and Semimembranosus muscles by means of Computer Vision techniques. The recognition of both muscles via MRI entails a low error rate (3 10%). A loss of weight in hams during the ripening process is related to a decrease in size (r(2)=0.992). The high correlation implies that the information obtained by means of Computer Vision techniques can be used as a non-invasive complement to the traditional processes of ham weighing and moisture estimation. PMID- 22061002 TI - Effects of ascorbic and citric acid on beef lumbar vertebrae marrow colour. AB - Citric acid was evaluated as a way of improving ascorbic acid's ability to stabilize beef lumbar vertebrae colour in high-oxygen packaging (MAP; 80% O(2)/20% CO(2)). Vertebrae were treated with citric acid (1%, 3%, or 10%), ascorbic acid (1%, 3%, or 10%), or a combination of both. Citric acid demonstrated no positive effects (P>0.05), compared with ascorbic acid, which inhibited (P<0.05) discolouration throughout the 7d display. Although ascorbic acid inhibited discolouration (visual colour and a(*); P<0.05), 3% and 10% ascorbic acid were most effective. However, if vertebrae are displayed for less than 7d, there may be no significant colour-stabilizing advantages associated with increasing ascorbic acid from 3 to 10%. The significant oxidizing effects of citric acid at 10% were reversed (P<0.05) by ascorbic acid. Combining citric and ascorbic acid had no synergistic affect (P>0.05) on vertebrae colour. PMID- 22061003 TI - Microstructural changes in Teruel dry-cured ham during processing. AB - Dry-cured ham, "Protected Designation of Origin (PDO)" Teruel, is a high quality meat product processed using a traditional dry-curing procedure. The objective of this paper was to study the microstructure of the Biceps femoris and Semimembranosus muscles during "PDO Teruel" dry-cured ham processing using electron microscopy techniques (Cryo-SEM, SEM and TEM). The Semimembranosus and Biceps femoris muscles from raw ham show the typical structure of muscle tissue in meat. The muscle fibres appear firmly attached to one another by the endomysial connective tissue; the myofibrils inside the cells are strongly attached to each other and to the sarcolemma. In raw ham, the typical structural elements that constitute the sarcomere can be observed by TEM. Important microstructural changes are observed following salting; reflected in the fact that the Z-disks inside the myofibrils are no longer in line and there is important degradation of the cell membranes in this stage. At the end of the process, an accumulation of solutes, which could be products from proteolysis occurring mainly in the last stage of ripening, could be observed in both muscles. Thus the proteolysis and dehydratation phenomena that take place during "PDO Teruel" dry-cured ham processing occur at an ultrastructural level, and this is the basis to produce a product with the sensory features appreciated by consumers. PMID- 22061004 TI - How many muscle samples are required to obtain reliable estimations of muscle fibre characteristics from pig longissimus muscle? AB - In order to investigate the reliability of muscle fibre trait estimations of pig longissimus muscle and to derive the minimum number of samples required per muscle cross-section and animal, intraclass correlation coefficients (ICC, theta^) were obtained by one-way analysis of variance. From each of 23 market weight pigs five samples, evenly distributed over the muscle cross-sectional area at the 12th/13th rib level, were taken and analyzed for various muscle fibre traits. The number of samples required per muscle cross-section was found to be different between selected fibre traits, ranging from a minimum of three (for number of muscle fibres) to a maximum of five or more (for mean fibre area, fibre type composition and relative area occupied by each fibre type). These findings should be taken as a recommendation, but their usefulness will depend upon the goal and conditions of future experiments. PMID- 22061005 TI - Carcass yield, composition and meat quality attributes of sheep and goat under semiarid conditions. AB - Carcass composition and meat quality attributes were compared in yearling sheep and goats. After weaning at 3 months of age, the animals were maintained under stall fed condition up to 1 year of age. Throughout the study, the animals were maintained on ad libitum complete feed (50:50 roughage and concentrate). The yearling sheep had higher (P<0.05) pre slaughter weight, hot carcass weight and dressing % than the goats. The muscular development as indicated by loin eye area was significantly (P<0.01) greater in sheep than goats. In general, total non carcass fat contents were more in sheep than goats. Similarly, the dissected total fat of half carcass was also more (P<0.01) in sheep than the goats. Neck and shoulder portion was heavier (P<0.01) in goats than the sheep. Shear force value was greater (P<0.01) in goats (7.42 kg/cm(2)) than sheep (3. 74 kg/cm(2)). Goat meat had more (P<0.01) moisture and less fat than mutton. In sensory evaluation both the species were rated almost equal in overall palatability scores. The current study showed that dressing yield was higher in sheep than goats. But goat yielded leaner carcass which is desirable for the calorie concern consumers. It was also revealed that meat from goat carcasses was tougher than mutton. PMID- 22061006 TI - Determination of potential inherent variability when measuring beef quality. AB - Probes, which can be used on-line to rapidly and efficiently detect beef quality attributes (colour and tenderness), are currently being considered to predict ultimate beef quality. The contribution of the inherent sampling variability (due to factors such as muscle location) needs to be evaluated in order to optimise the sampling procedure for these measurements. The main objective of this trial was to monitor some sampling factors which may contribute to variation in pH and various quality attributes in bovine M. longissimus thoracis et lumborum (LTL). Location along the muscle did not impact on colour measurements (P?0.05). Location had no effect on cook loss, Warner Bratzler shear force (WBSF) and sarcomere length values (P?0.05). The moisture and intramuscular fat contents did vary (P?0.05); however, as the differences were very small this may not be of practical significance. Different models of pH meters/probes had a significant influence (P?0.01) on recorded pH values. However pH did not differ significantly (P?0.05) along the length of the LTL. The type of meter used also had a significant impact on colour readings and 1 h 'blooming' time was observed as optimal for measuring colour on beef. PMID- 22061007 TI - Effects of conjugated linoleic acid on color and lipid oxidation of beef patties during cold storage. AB - The effects of conjugated linoleic acid (CLA) on color and lipid oxidation of beef patties were investigated. Ground beef was divided into three batches. The control patties were prepared with 90% lean meat and 10% tallow. The second treatment consisted of 90% lean meat with 9.5% tallow+0.5% CLA sources. The third treatment consisted of 90% lean meat with 8% tallow+2% CLA sources. The patties were wrap-packaged and then stored at 4 degrees for 14 days. The CLA concentration significantly increased (P<0.05) by substituting CLA sources for fat. Storage of the patties did not alter the CLA concentration in beef patties. The treatment substituted with CLA sources had significantly lower TBARS (2 thiobarbituric acid-reactive substances) values (P<0.05) than the control. For oxymyoglobin contents and a* value, substituted CLA sources treatments had significantly higher values than the control. However, L* value significantly increased by substituting CLA sources for fat. PMID- 22061008 TI - A comparison of halothane homozygous negative and positive pietrain sire lines in relation to carcass and meat quality, and welfare traits. AB - Barrows (n=164) and gilts (n=249) from crosses of a Pietrain homozygous halothane recessive (Pi nn) and two Pietrain homozygous dominant (Pi NN-a and Pi NN-b) sire lines with Landrace*Large White NN sows, were used to study the effect of terminal sire and pre-slaughter treatment on meat quality and animal welfare. The pigs from each of the two farms where they were finished were delivered to the abattoir in two batches differing in the pre-slaughter conditions. A total of 90 pigs (54 NN and 36 Nn) were assigned to a long pre-slaughter treatment (6 h transport and 14.5 h lairage) and 89 (57 NN and 33 Nn) to a short pre-slaughter treatment (4.5 h transport and 2.5 h lairage) in Farm 1, and 118 (65 NN and 53 Nn) to the long (7 h transport and 14 h lairage) and 114 (66 NN and 48 Nn) to the short pre-slaughter treatment (1.5 h transport and 2 h lairage) in Farm 2. In Farm 1, heart rate of 3 NN and 3 Nn gilts was recorded throughout loading and transport and blood samples from 5 NN and 5 Nn were collected before loading and after transport to measure cortisol, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH). Carcasses were classified and commercial cutting was carried out. At 24 h, meat quality was assessed on the Longissimus thoracis muscle by measuring electrical conductivity (PQM), colour (Minolta CR 200 and Japanese scale), pHu and drip losses. Halothane carriers showed a higher mean heart rate and higher increase in CPK levels (P<0.05) after transport in the short pre slaughter treatment than halothane free pigs. No effect was observed in cortisol or LDH values. Pi NN-a sired pigs had a higher live and carcass weight (P<0.001) and loin depth (P<0.05), but lower killing out percentage (P<0.01) and leg yield (P<0.01) compared with the progeny of the other two terminal sires. Gilts were leaner (P<0.001), had a higher killing out percentage (P<0.001) and higher yields of primal cuts (P<0.001) compared with barrows. Pi nn sired pigs had poorer meat quality (higher PQM values in both farms, P<0.01) than Pi NN-a sired pigs. Long pre-slaughter treatment resulted in darker meat (P<0.01) in both farms and in higher pHu (P<0.001) in Farm 1 than short pre-slaughter treatment. Conversely, pigs subjected to the short pre-slaughter treatment showed higher PQM values (P<0.01) in Farm 1 and higher PSE percentage (P<0.05) in both farms compared to the ones subjected to the long pre-slaughter treatment. These results suggest that Pietrain halothane free sire lines could produce similar results on carcass quality to halothane carriers, without compromising meat quality and welfare. PMID- 22061009 TI - Effect of NaCl on lipid peroxidation-derived aldehyde, 4-hydroxy-2-nonenal formation in minced pork and beef. AB - Pork and beef containing NaCl were stored at 0 degrees C and changes in 4 hydroxynonenal (HNE) content were analyzed after 0, 3, 7 and 10 days. As an index of the lipid peroxidation level, malonaldehyde (MA) content was also analyzed. In pork, HNE content in samples with 2% NaCl increased (P<0.05) after 7 and 10 days of storage. In beef, HNE content in all samples increased during storage. The HNE content in samples with NaCl was higher than those of the control, after 7 and 10 days of storage, although the difference was not always significant. Judging from MA content, NaCl may act as a pro-oxidant in pork and beef. HNE may accumulate in pork and beef in which lipid peroxidation is progress. PMID- 22061010 TI - Changes in fatty acids and microbial populations of pork inoculated with two biopreservative strains. AB - Meat surface fermentation has been reported as an efficient method to reduce undesirable microbial population of this food commodity in tropical areas with high ambient temperatures and humidity. However, in order to efficiently apply this method, growth of biopreservative strains and changes in the meat substrate should be studied. Changes in long-chain fatty acids as well as pH and microbial growth (lactic acid bacteria and enterobacteria) were studied in pork inoculated with two biopreservative strains (Lactobacillus alimentarius and Staphylococcus carnosus) and stored at 4 and 20 degrees C. Both tested strains produced more than 6 mg lactic acid/g tissue, however, S. carnosus was more efficient in reducing enterobacteria populations at 20 degrees C. No significant increase in long-chain fatty acid concentration in samples stored at 4 degrees C was observed but there was a rapid increase of free fatty acids when stored at 20 degrees C. PMID- 22061011 TI - Glutathione peroxidase activity, and content of total and soluble selenium in five bovine and porcine organs used in meat production. AB - Glutathione peroxidase (GSHPx) activity, and total and soluble selenium content were compared in five bovine and porcine organs. The highest GSHPx activity in porcine tissues was found in the liver (35.0 U/g), spleen (29.3 U/g) and kidney (27.3 U/g) with much lower values in the heart (1.8 U/g) and diaphragm (0.8 U/g). A different pattern with lower inter-organ variation in GSHPx activity was observed in cattle: kidney (8.5 U/g), spleen (8.0 U/g), heart (5.8 U/g), liver (4.0 U/g) and diaphragm (2.1 U/g). The total selenium content was similar in both species with the highest content in the kidney (1764 and 1665 ng/g; pig/bovine), followed by liver (533 and 307 ng/g), spleen (370 and 284 ng/g), heart (201 and 205 ng/g) and diaphragm (144 and 116 ng/g). The percentage of soluble selenium varied more among the pig organs (46-94%) than among bovine organs (61-75%). The results show a marked variation in the activity of the selenium-containing GSHPx among organs and species in spite of a similar rank order of selenium content in the two species. Since GSHPx has a role in food stability and the intake of selenium is marginal in many European countries, the results add to the background information concerning the use of selenium rich organs as human foods. PMID- 22061012 TI - The effects of electrical stunning and percussive captive bolt stunning on meat quality of cattle processed by Turkish slaughter procedures. AB - The effects of electrical and percussive captive bolt stunning both on initial and up to 14 days post mortem meat quality of Friesian young bulls were studied. The first group (NS; n=10) were slaughtered without stunning under Turkish slaughter procedure (these animals were slaughtered under conditions acceptable to the appropriate ethics committee) in a modern abattoir. In the second group (ES; n=10) animals were electrically stunned. In the third group (PS; n=10) animals were stunned with percussive captive bolt. Meat quality was assessed by examining muscle glycogen concentration, pH and WHC. Also cooking loss, texture parameters and consumer sensory properties were assessed at 24 h, 4, 7 and 14 days post mortem. Meat colour as L(*), a(*), b(*), C(*), h(*) values were evaluated at 0, 48 h, 3, 5, 7, 9 and 14 days post mortem. Pre-slaughter handling affected muscle glycogen concentration (P<0.05). Animals in electrical and percussive captive bolt stunned groups had higher muscle glycogen concentrations compared to animals in the non-stunned group (P<0.05). Although pre-slaughter handling did not affect significantly pH(24 h) and WHC, differences were significant for cooking loss, colour coordinates and texture parameters at some storage times. For all sensory attributes (odour, flavour, tenderness and overall acceptability) at all ageing periods (24 h, 4, 7 and 14 days) the percussive stunned (PS) group was significantly superior to the non-stunned (NS) group. The electrically-stunned (ES) group also tended to be superior to the NS group although not all differences were statistically significant. These results indicate that percussive captive bolt stunning of cattle improved meat quality compared with cattle electrically stunned using head only tongs and those non stunned under approved Turkish slaughter procedure. PMID- 22061013 TI - Effect of food grade organic acids on inoculated S. aureus, L. monocytogenes, E. coli and S. Typhimurium in sheep/goat meat stored at refrigeration temperature. AB - Sheep/goat forequarters procured from freshly slaughtered animals were decontaminated with hot water and inoculated with Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella typhimurium. The forequarters were individually spray washed with 2% lactic acid and 1.5% acetic + 1.5% propionic acid combination. Total viable count (TVC) of the treated meat samples was reduced by about 0.52 and 1.16 log units with marginal changes in colour and odour scores. Inoculated organisms were found to be highly sensitive to acid combination treatment as compared to lactic acid alone. Shelf-life of acid and acid combination treated samples was increased to 8 and 11 days as against 3 days in untreated samples. Carcass washing with acid alone or acid combination was found to be suitable for extension of shelf-life and improvement in the sensory and microbiological quality of meat. PMID- 22061014 TI - Microstructural changes in rabbit meat wrapped with Pteridium aquilinum fern during postmortem storage. AB - This work studied the microstructural degradation of rabbit semimembranosus muscle wrapped with Pteridium aquilinum fern fronds, stored at 4 degrees C during the first 72 h postmortem. At the microstructural level, practically all the perimysial and endomysial connective tissue was destroyed and a small degradation of the myofibrils could be observed after the first 24 h postmortem; in addition, a degradation of the sarcolemma and the generation of numerous gaps were seen. After 32 h postmortem, tissue fibres were broken, cell membranes were more strongly degraded, and the connections between the sarcolemma and the myofibrils had disappeared. After 72 h postmortem, intercellular connections became degraded inside the muscle bundles and intercellular gaps became larger. The proteolytic activity is attributed to fern endogenous enzymatic activity in addition to the typical endogenous enzymatic activity of meat postmortem. PMID- 22061015 TI - The influence of season on quality characteristics of hot-boned beef m. longissimus thoracis. AB - Samples of m. longissimus thoracis (LT) muscle were randomly collected from 70 Omani beef cattle 1 h after slaughter between August 2001 and July 2002 in the Muscat Municipality central slaughterhouse to investigate the effect of seasonal parameters on meat quality during the hot and cool seasons of Oman. The collection period (12 months) was divided into two seasons according to ambient temperatures and relative humidity and termed: Cool Season (November-March with average temperature of 21.2+/-1.40 degrees C and 57.9+/-1.61% relative humidity) and Hot Season (April-October with average temperature of 34.3+/-1.67 degrees C and 48.8+/-7.57% relative humidity). The season had a significant effect on meat quality characteristics of the LT muscle. Muscles collected during the hot season had significantly (P<0.001) higher ultimate pH values (6.24) with significantly (P<0.001) lower Warner-Bratzler (WB) shear force values (10.12) than those collected during the cool season (5.54 and 15.58). In these hot-boned samples, there was a linear relationship between ultimate pH and WB shear values. Cooking loss was significantly (P<0.001) higher for cool season samples (26.01%) than from hot season samples (19.75%). Beef from the hot season group had significantly (P<0.001) darker meat than that of the cold season group, based on L* (31.45 vs 35.58), a* (18.53 vs 23.19) and b* (4.16 vs 6.40) colour measurements. There was a linear relationship between ultimate pH and cooking loss, L*, a* and b*. These results indicated that heat stress (>30 degrees C) lead to physiological stress in beef cattle, which in turn increased muscle ultimate pH and influenced related meat quality characteristics. PMID- 22061016 TI - Comparative effect of low levels of dietary cobalt and parenteral injection of vitamin B(12) on carcass and meat quality characteristics in Omani goats. AB - The effect of low levels of dietary cobalt (Co) on carcass and meat quality characteristics were investigated in 36 male goats of three different Omani breeds namely Batina, Dhofari and Jabal Akdhar. Goats were randomly divided into two groups at 10 weeks of age, control (18 animals) and treated (18 animals). Goats from both groups were fed Rhodesgrass hay and a commercially prepared diet containing 0.10 and 0.12 mg Co/kg DM, respectively from 10 to 46 weeks of age. Animals in the treated group were supplemented with subcutaneous injections of 2000 MUg of hydroxocobalamin (vitamin B(12)) on week 10 and thereafter for 46 weeks at 8-week intervals. At 46 weeks of age, the animals were slaughtered and their carcass and meat quality characteristics compared. Serum vitamin B(12) levels were significantly higher in goats from the treated group from week 16 till the end of the experiment. The final live and carcass weights were significantly higher (P<0.05) for the treated Batina group by 13.4 and 8.3% compared with the control group, respectively. Shoulder, rack, loin and leg cut weights were also significantly higher (P<0.05) for the Batina treated group compared with the control group by 14.7, 16.8, 12.8 and 13.1%, respectively. Carcass length, leg length, width behind shoulder, maximum shoulder width and longissimus muscle area were significantly higher (P<0.05) for the Batina treated breed than for the control group by 6.7, 5.8, 10.1, 10.1 and 28.5%, respectively. Four muscles (Mm. longissimus dorsi, biceps femoris, semimembranosus, and semitendinosus) from treated and control groups were evaluated for ultimate pH, expressed juice, cooking loss%, colour (L*, a* and b*), and Warner-Bratzler shear force values. There were significant treatment effects on these muscle quality characteristics for the Batina breed only. Muscles from the treated group showed significantly lower (P<0.05) shear force values of between 15 and 27% than those from the control group. Moreover, the treated Batina goats tended to have significantly lower (P<0.05) ultimate pH, expressed juice, L* and higher a* values than those from the control group for longissimus dorsi and biceps femoris muscles only. PMID- 22061017 TI - Chemical and microbiological parameters and sensory attributes of a typical Sicilian salami ripened in different conditions. AB - A study was carried out on a typical Sicilian salami prepared from meat of the local Nero Siciliano pig in order to characterize this typical product. One formulation of salami was divided in two batches and ripened in two different environments, a traditional sicilian room (TR) and a controlled industrial ripening room (RR). Microbiological and physico-chemical analysis were performed on raw mixture and after 7 and 90 days of ripening. Sensory analysis was carried out on salami at the end of ripening, and flavour compounds were extracted by simultaneous distillation-extraction and analysed by gas chromatography/mass spectrometry. Commercial salami prepared from meat from white pig were purchased locally and used as comparative samples. The experimental salami at the end of ripening was characterized by a high level of fat and low level of moisture. Fatty acid analysis showed that experimental salami contained a higher percentage of oleic acid, vaccenic acid and palmitic acid and a lower percentage of stearic acid and linoleic acid, when compared to commercial salami (P<0.05). No significant differences were found in fatty acid composition of the experimental salami between the two types of ripening. Instrumental analysis of flavour volatile compounds in the experimental salami demonstrated that traditionally ripened salami contained the most volatiles, especially aldehydes (8217 vs. 3104 ng g(-1), P<0.05). Sensory analysis showed no significant differences as a consequence of different ripening conditions for firmness, saltiness, acidity, cohesiveness and elasticity. In contrast, there were significant differences for hardness and rancidity, which were higher in TR salami compared with RR and commercial salami. Lactic acid bacteria and Micrococcaceae counts were higher in controlled ripened salami although the hygienic quality of both products was satisfactory. The use of a controlled room for the ripening of this typical salami seems to be a potential technological improvement to maintain an all year around production of this salami, that otherwise cannot be produced in the summer period due to the higher environmental temperatures. However, the non traditionally ripened product showed some chemical differences that were not evidenced by sensory analysis. PMID- 22061018 TI - Effects of housing conditions of slaughter pigs on some post mortem muscle metabolites and pork quality characteristics. AB - The results of two experiments studying the effects of housing conditions on post mortem muscle metabolism and meat quality are presented. In the first experiment slaughter pigs (n=71) from two different crossings, were raised at a density of 0.7 m(2)/animal (10 pigs/pen) either with (enriched) or without (conventional) a bedding of daily fresh straw. In the second experiment, animals (n=60) were reared under either conventional or free range housing (1.25 m(2)/animal, 30 pigs per pen) conditions. Main differences between conventional and enriched housed pigs were found in the biceps femoris (BF) muscle, and related to temperature, drip loss and colour. Association studies revealed that there were significant correlations between early (0-4 h) post mortem muscle pH and glycogen and lactate concentrations and between muscle pH measured at 1 h post mortem and muscle rigidity, expressed as the rigor value. There were significant differences with respect to meat quality and post mortem metabolism of the longissimus lumborum (LL), between conventional and free-range pigs. Early post mortem pH (0-4 h) was highest in the free-range pigs, due to low lactate concentrations. The relatively fast pH decline in the conventionally housed group resulted in increased amounts of water exuding from the meat, as measured by the filter paper method. The ultimate pH, was lowest in the free-range animals. The differences in ultimate pH, however, had no effect on drip or cooking losses. It can be concluded from these results that enrichment of the housing system has little effect on the course of the post mortem metabolism and meat quality. However, increasing the freedom of movement by applying lower stocking densities, affects the post mortem muscle metabolism, resulting in reduced water exudation. Correlations up to 0.7 between energetic parameters are not sufficiently high to be useful to predict meat quality of individual carcasses. PMID- 22061019 TI - The effect of dietary CLA supplementation on meat and eating quality, and the histochemical profile of the m. longissimus dorsi from stress susceptible fatteners slaughtered at heavier weights. AB - The influence of adding 2% CLA to the morning feed of a group of 20 crossbred fatteners from 70 to 130 kg on meat quality, eating quality and dietetic value of m. longissimus dorsi was evaluated compared with a group of 20 controls. Addition of 2% CLA in feed did not influence fattening and slaughter results and also some traits of meat and eating quality. The only significant differences were observed in dry matter content, in meat flavour and L(*), b(*), and hue angle value. Meat from fatteners from the experimental group had a statistically significant higher content of CLA (P?0.01) and lower content of unsaturated fatty acids especially C18: 2, C18: 1 and C20: 4, PUFA fatty acids (P?0.01) and a reduction in the ratio of n-6: n-3 PUFA (P?0.01). No statistically significant influence of CLA on the content of cholesterol was observed. The results of the current histochemical study showed that dietary CLA supplementation significantly increased both the number and diameter of white fibres, and correspondingly reduced the number and diameter of red fibres. The percentage and diameter of intermediate fibres was unaffected by CLA. PMID- 22061020 TI - Effect of blade tenderization and tumbling time on the processing characteristics and tenderness of injected cooked roast beef. AB - The combined effect of blade tenderization (T, NT) and tumbling time (0, 2, 16 h) on quality characteristics of cooked beef roasts processed with 20 or 40% injection level was investigated. Properties of the beef roasts were determined by measuring processing and textural characteristics (shear force, texture profile analysis). Extended tumbling (to 16 h) favorably affected hydration properties and thermal stability, yielding lower cooking loss and purge and higher WHC for beef roasts. It also decreased shear force and hardness of beef samples by 50-60%, but was unable to increase cohesiveness. Blade tenderization prior to injection generally was found to be beneficial for textural characteristics, tended to improve cook yield, but did not influence other hydration properties. An interaction between tenderization and tumbling was observed for shear force. Blade tenderization decreased shear values by 15-20% for roasts tumbled for 0 or 2 h, but did not improve tenderness with extended tumbling. PMID- 22061021 TI - Effect of Duroc content, sex and ageing period on meat and eating quality attributes of pork loin. AB - This study was conducted to determine the effect of percentage Duroc content of entire male and female pigs and ageing period on meat and eating quality attributes of pork loin (M. longissimus thoracis et lumborum). A total of 84 pigs [entire males (n=42) and female (n=42)] of 0% Duroc (100% Large White), 50% Duroc (Duroc*Large White) or 100% Duroc (n=14 pigs per sex*genotype combination) were slaughtered at a liveweight of ~100 kg. Steaks from the M. longissimus lumborum of female pigs were aged for either 2 or 7 days post-slaughter and evaluated using a consumer taste panel. Eating quality attributes of tenderness, flavour and overall liking of pork loin steaks from female pigs were not (P>0.05) influenced by Duroc content. Pork from 100% Duroc pigs was juicier (P=0.05) and had a higher (1.84%, P=0.05) intramuscular fat content than pork from 0 and 50% Duroc pigs (1.40 and 1.25%, respectively). Pork from entire male pigs had a lower (P<0.001) intramuscular fat content, was darker (P<0.01) in colour and recorded higher (P<0.01) Warner Bratzler shear force values compared with pork from female carcasses. Ageing pork loin steaks in vacuum bags for 7 days improved tenderness (P<0.01), flavour (P<0.05) and overall liking (P<0.05) compared with steaks aged for 2 days post-slaughter. Ageing of pork steaks for 7 days post-slaughter improved eating quality attributes far more effectively than increasing percentage Duroc content of pigs, which only influenced consumer scores for juiciness. PMID- 22061022 TI - Factors associated with surface iridescence in fresh beef. AB - The objective of this study was to investigate factors associated with surface iridescence in fresh beef. Eight muscles were evaluated for occurrence of surface iridescence: Biceps femoris (BF), Gluteus medius (GM), Longissimus lumborum (LD), Psoas major (PM), Rectus femoris (RF), Semimembranosus (SM), Semitendinosus (ST), and Tensor fasciae latae (TF). Incidence of surface iridescence was 91% for ST, 34% for SM, 27% for LD, 20% for GM, 12% for RF, 9% for BF, 8% for TF, and 6% for PM (P<0.05). Factors associated with surface iridescence in the ST were further examined because iridescence was observed to a much higher degree in the ST as compared with other muscles evaluated. Greater ST surface iridescence was associated with larger ribeye areas, more youthful lean maturity scores, higher L(*), a(*) and b(*) colorimeter values, lower ultimate pH values, and faster cooking (P<0.05). PMID- 22061023 TI - Prediction of suckling lamb carcass composition from objective and subjective carcass measurements. AB - Correlations and regression between fatness and carcass conformation measurements and carcass tissue composition has been studied for both sexes in suckling lambs, with slaughter weights between 9 and 15 kg. Objective fat measurements showed higher correlations than subjective fat measurements, mainly with carcass fat. Conformation measurements presented greater correlations with tissues weight than with tissues proportion (r?0.50). CCW was highly correlated with total muscle in the carcass (R(2)=0.961). Two fatness measurements (KKCF proportion and dorsal fat thickness) were included for the prediction of the muscle proportion. Furthermore, the model included other measurements, such as fore cannon bone weight and internal carcass length although they displayed very low correlation coefficients. This equation explained 64.1% of the variation of carcass muscle proportion (r.s.d.=1.532). CCW was included in the prediction equations of tissue weights, although in the fat tissue equation it appeared in the form of the carcass compactness index (CCW/L). CCW was a good predictor of the weight of carcass tissues in suckling lambs, especially for muscle. Prediction equations for tissue composition in grams were more accurate (R(2)?0.91) than those for tissue proportion. When gender was included in all models it did not improve either accuracy or precision of the prediction. PMID- 22061024 TI - Preliminary investigation of the application of Raman spectroscopy to the prediction of the sensory quality of beef silverside. AB - The potential of Raman spectroscopy for the determination of meat quality attributes has been investigated using data from a set of 52 cooked beef samples, which were rated by trained taste panels. The Raman spectra, shear force and cooking loss were measured and PLS used to correlate the attributes with the Raman data. Good correlations and standard errors of prediction were found when the Raman data were used to predict the panels' rating of acceptability of texture (R(2)=0.71, Residual Mean Standard Error of Prediction (RMSEP)% of the mean (MU)=15%), degree of tenderness (R(2)=0.65, RMSEP% of MU=18%), degree of juiciness (R(2)=0.62, RMSEP% of MU=16%), and overall acceptability (R(2)=0.67, RMSEP% of MU=11%). In contrast, the mechanically determined shear force was poorly correlated with tenderness (R(2)=0.15). Tentative interpretation of the plots of the regression coefficients suggests that the alpha-helix to beta-sheet ratio of the proteins and the hydrophobicity of the myofibrillar environment are important factors contributing to the shear force, tenderness, texture and overall acceptability of the beef. In summary, this work demonstrates that Raman spectroscopy can be used to predict consumer-perceived beef quality. In part, this overall success is due to the fact that the Raman method predicts texture and tenderness, which are the predominant factors in determining overall acceptability in the Western world. Nonetheless, it is clear that Raman spectroscopy has considerable potential as a method for non-destructive and rapid determination of beef quality parameters. PMID- 22061025 TI - Physical changes of significance for early post mortem water distribution in porcine M. longissimus. AB - The post mortem changes in water mobility and distribution were followed in porcine muscle (M. longissimus dorsi) samples using continuous low-field NMR relaxation measurements and simultaneous measurement of changes in muscle impedance as an indirect measure of membrane integrity as well as muscle contraction measurements using a rigormeter instrument. Distributed exponential fitting analysis of NMR T(2) relaxation data revealed the presence of three distinct water populations (T(20), T(21), T(22)) within the muscle during its conversion to meat. Comparison of T(2) relaxation patterns and contraction data indicates that rigor development affects the attributes of the T(21) water population and thereby contributes to myofibrillar water characteristics post mortem, as the T(21) water population is believed to reflect inter/intra myofibrillar water. The volume of the water population believed to reflect extra cellular water (T(22)) in the living muscle. Early post mortem T(22) decreased slightly within the first 2-3 h post mortem followed by an increase and a change in its characteristic time constant. This was ascribed to an initial muscle cell swelling followed by water being expelled from the cellular space into the extra myofibrillar space. Comparison of changes in the T(22) water population and impedance characteristics within the muscle during its conversion to meat revealed close relationship between progresses in the two attributes. Obtained data strongly support that the post mortem reorganization of water is closely associated with membrane properties, which moreover was found to affect the final water-holding capacity of the meat. Finally, a model for early post mortem events leading to changes in the distribution of water within muscles is proposed. PMID- 22061026 TI - The effects of slaughter weight, breed type and ageing time on beef meat quality using two different texture devices. AB - Physical characteristics of meat texture were measured on the M. longissimus dorsi of 103 entire yearling bulls in terms of the effect of slaughter weight (300 or 550 kg), breed type (double muscle, fast growth, dual purpose and unimproved) and ageing time (1, 7 and 21 days). Live weight, breed and ageing effects were statistically significant for all the Warner-Bratzler variables measured on cooked meat. For compression values (raw meat), live weight had a significant effect at higher compression rates, which were higher in the heaviest animals, and ageing had a significant effect at lower compression rates, which were progressively lower as ageing time increased. Breed effect was significantly different for all compression values. At the highest rates of compression, unimproved and dual purpose breed types had the highest values. At 20% compression, double muscled animals had the lowest values, but only at one day of ageing. The differences between breed types tended to decrease or disappear with longer periods of ageing. PMID- 22061027 TI - Methodology for measuring malonaldehyde as a product of lipid peroxidation in muscle tissues: A review. AB - The purpose of this review is to summarize concerns regarding the formation and quantification of malonaldehyde as a product of lipid peroxidation in muscle tissues. The spectrophotometric thiobarbituric acid (TBA) method is the most frequently used test for malonaldehyde quantification, especially in muscle tissues, as a marker of lipid peroxidation. However, the TBA method has been criticized as lacking specificity and adequate sensitivity towards malonaldehyde. High performance liquid and gas chromatographic methods offer better specificity and sensitivity for malonaldehyde detection. The TBA method, however, may be preferred over the chromatographic method because of its simplicity, especially when a large number of samples need to be analyzed in a short period of time on a daily basis. In addition, the TBA method has been correlated with other objective and subjective methods of measuring lipid peroxidation and its specificity can be improved with the use of a solid phase extraction C(18) cartridge. PMID- 22061028 TI - The effects of antioxidative treatments on mutton flavour/odour intensity and species flavour differentiation. AB - This study examined the effects of curing and oxygen exclusion on the odour and flavour of sheepmeats. One series of experiments examined the effect of curing on the ability of panellists to distinguish between the flavours of lean mince from various species (mutton, beef, pork, chicken). Other experiments examined the effects of curing and of maintaining an anoxic storage/cooking environment on the intensity of mutton flavour and odour, particularly adipose tissue odour. Curing had no effect on panellists' abilities to distinguish between the flavour of mince from different species. Storage and cooking of uncured mutton adipose tissue samples under anoxic conditions limited lipid oxidation but enhanced mutton odour intensity. Nitride had a pro-oxidant effect on mutton adipose tissue stored in air. There was no corresponding effect on mutton odour intensity. These findings suggest that lipid oxidation products contribute very little to mutton odour from adipose tissue, and possibly also to species flavour differences in lean meats. PMID- 22061029 TI - Comparisons of the effect of electrical stimulation methods on postmortem pH decline in beef muscle. AB - Results of four electrical stimulation (ES) studies were summarized to demonstrate the impact of different ES parameters on pH decline patterns in postmortem M. longissimus thoracis et lumborum. Postmortem pH decline was modeled as a non-linear function of time, and estimates of minimum obtainable pH, pH decline rates, and time to reach pH 6.0 were compared for each study. The decline model for study 4 (AC, 60 Hz, 50 V; 5 min post mortem) had a larger (P < 0.05) estimate for decline rate than that for study 1 (AC, 60 Hz, 400 V; 1 h post mortem) and the control (non-stimulated) data. The model estimate of time to pH 6.0 (0.56 h) for study 4 was the shortest (P < 0.05) for all treatments. Different ES parameters produce different pH decline patterns post mortem and, therefore, may impact product quality and fabrication and chilling protocols adopted in fresh beef processing. PMID- 22061030 TI - Influence of repeated restraint and isolation stress and electrolyte administration on carcass quality and muscle electrolyte content of sheep. AB - Crossbred lambs were assigned, within weight blocks, to one of four treatments applied in a 2 * 2 factorial design (n = 6 per treatment). Treatment main effects included no stress (NS) or three consecutive days of restraint and isolation stress (RIS) and treatment with either water (W) or electrolytes (E). The experimental design resulted in four treatments, namely NS-lambs given W, NS lambs given E, RIS-lambs given W, and RIS-lambs given E. Stress treatment consisted of moving each lamb from its home stanchion to a separate location and isolation from visual and tactile contact with other lambs for 6 hours daily for 3 days before slaughter. All lambs received a 320 ml oral drench of either W or E on each day after the stress treatment. Stress treatment reduced (P < 0.05) semitendinosus (ST) muscle glycogen by 4.8-fold. At 24 h post mortem, muscle pH for semimembranosus (SM), biceps femoris (BF) and infraspinatus (IF) was higher (P < 0.05) in RIS-lambs that in NS-lambs. Hunter L(*)a(*)b(*) values, measured on muscle cross-section, revealed a lighter (P < 0.05) BF; more (P < 0.05) red BF, ST, and longissimus dorsi (LD); and more (P < 0.05) yellow ST, SM, BF, and LD for NS-than for RIS-lambs. Muscle from RIS-lambs contained less (P < 0.05) potassium than that from NS-lambs. Restraint and isolation stress of lambs resulted in a reduction in muscle glycogen, but only slight increases in ultimate pH and minimal influences on muscle color. Administration of electrolytes had no effect on lamb carcass quality. PMID- 22061031 TI - A relationship between bovine fat colour and fatty acid composition. AB - Subcutaneous adipose tissue was obtained from pasture-grazed (n = 13) and short term (70 days) grain-fed (n = 13) cattle. The yellow colour of the adipose tissue was assessed by Minolta b(*) value readings and by determination of total carotenoids and the two measurements gave a correlation coefficient of 0.79 (P < 0.01). The fatty acid composition of the samples varied with fat colour. As the b(*) value and the carotenoid content of the fat increased, there was a significant increase in the total percentage of cis mono-unsaturated fatty acids and a decrease in saturated fatty acids (P < 0.01). Consequently, the ratio of cis mono-unsaturated to saturated fatty acids was found to be higher in those samples exhibiting a greater yellow colour. PMID- 22061032 TI - Tenderness of ovine semimembranosus: Is collagen concentration or solubility the critical factor? AB - The concentration and heat-dependent solubility of collagen were measured in the semimembranosus (36 animals) and, for comparison, the gluteus (108) muscles of sheep aged 4 months to 5 years. For both muscles, solubility declined with age but concentration remained unchanged. Compared to gluteus and other major ovine muscles, the semimembranosus had markedly insoluble collagen at a relatively low concentration. To assess the relative importance of collagen concentration and solubility on tenderness/texture for a muscle with this profile, the semimembranosus muscles contralateral to those used for collagen analysis were cooked to an endpoint of 75 degrees C and assessed by sensory panel and Warner Bratzler shear tests. The panel data showed that collagen concentration was the more important determinant of eating quality, whereas shear data were more clearly related to solubility. The implications of the sensory results are discussed for muscles that contain a different collagen profile. PMID- 22061033 TI - Special treatment during slaughtering in Finland of cattle carrying an excessive load of dung; Meat hygienic aspects. AB - The aim of the study was to evaluate the microbiological consequences of the Finnish special hide regulations. These were agreed upon, by a committee including members representing meat production, industry and the state, to reduce the number of cattle carrying excessive loads of dung. The changes in the number of excessively dungy cattle in one beef abattoir have been recorded since the adoption of the special rules. The effect of excessive dunginess of the hide on microbial contamination of the carcasses was measured in the same abattoir using excision sampling technique. From 1983 to 1990 the proportion of excessively dungy cattle has decreased 85%, with the majority of them arriving from October to March. Excess dunginess resulted in statistically significantly increased microbial contamination at both sampling sites. Results indicate that the regulations are reasonable from the point of view of meat hygiene and that, for commercial-scale slaughtering, the drawbacks caused by the excess dunginess of the hide cannot be compensated for by greater care in the work procedures. PMID- 22061034 TI - Effects of starter cultures on the biochemical characteristics of French dry sausages. AB - Bacterial starter cultures, consisting of lactic acid bacteria (Lactobacillus, Pediococcus) and staphylococci (Staphlylococcus carnosus. S. saprophyticus, S. warneri), have an important effect on the pH, lactate, acetate and free fatty acid contents of sausages. Sausages made with L. sake had the lowest pH whereas no change of pH was noticed in the controls and in the sausages inoculated with P. acidilactici. Inoculation of S. saprophyticus led to sausages with a high acetate content. Lipolysis occurred not only in inoculated samples but also in the controls, but it was the highest in the sausages inoculated with S. warneri. PMID- 22061035 TI - Effects of biological source on cooking and palatability attributes of beef produced for the Japanese market. AB - Boneless beef loin samples from five biological sources (Japanese Wagyu, American Wagyu (3 4 - 7 8 Wagyu), Angus, Longhorn and US Choice) were evaluated for cooking and palatability attributes as shabu-shabu, steaks and roasts. Japanese Wagyu beef was superior in palatability compared to Angus, Longhorn and US Choice beef when prepared as shabu-shabu or as steaks. Very palatable beef was produced for the Japanese market when the Wagyu breed and a controlled, extended feeding period were utilized. The results were more equivocal when the beef was prepared as roasts, but it is unlikely that a substantial demand for roasts will develop in Japan due to high retail costs and traditions in cookery. PMID- 22061036 TI - The effect of preheated tendon as a lean meat replacement on the properties of fine emulsion sausages. AB - Tendon from beef hind leg muscles was used to replace some of the lean in a conventional emulsion formulation. The tendon was homogenized and either used raw or preheated for 2.5 h at a range of temperatures (50, 60, 70, 80 degrees C) before use. Texture analysis and sensory evaluation were performed on cylinders of cooked sausage. Texture analysis was carried out on formulations which had 20% of meat protein replaced by 20% tendons which were raw or had been preheated to 50, 60, 70, or 80 degrees C. Fracturability decreased by about 40% with raw tendon, but was restored to within 20% of the no-replacement control if the tendon had been preheated. Hardness was approximately doubled by replacement with raw tendon or tendon heated at 50 degrees C. At temperatures higher than that, hardness returned to approximately no-replacement levels. For sensory evaluation (0-25% replacement; preheating at 70 degrees C), sausages were assessed by a 12 member panel for texture, flavour and overall acceptability. All attributes decreased with increasing collagen content, the decrease being less marked with preheated tendon. Thus more connective tissue could be added for the same panel score if the tissue was preheated. Comparison of the texture profile and the panel scores for texture at the same lean replacement level suggested that reduced fracturability was the texture parameter that panellists objected to when heated tendon replaced some of the lean. Other researchers have shown that connective tissue preheated to 100 degrees C before addition in emulsion sausages results in improved yields and better sensory attributes, but the present results show that temperatures as low as 60 degrees C can be effective for beef tendon. PMID- 22061037 TI - Effects of fattening on post-mortem pH of beef muscles. AB - The pH of beef psoas major (PM) and longissimus dorsi (LD) muscles at 1.0 h after slaughter were examined among the following four groups: pithed fattening cattle (FP), non-pithed fattening cattle (FN), pithed calves (CP) and non-pithed calves (CN). Differences were observed only in PM muscles. The levels of pH were in the order of FP2%) of stable chromosomal anomalies with loss of telomere integrity was observed in cases with late complications. A significant decrease (P <= 0.001) in enzyme activity of complex II, III, and IV of mitochondrial respiratory chain was evident in both diabetic groups in comparison with healthy controls. Activation in the cascade of nuclear factor kappa-beta (NF-kappabeta)-mediated feed-forward proinflammatory cytokine response was noted among T2DM subjects. Increased oxidative stress, mitochondrial membrane depolarization, activation of caspase-3, and PARP observed in diabetic groups indicated bax triggered mitochondrial mediated cellular apoptosis. Our results provide the first insights of lymphocyte mitochondrial dysfunction that might be helpful in explaining the clinical significance of immunologic perturbation observed in type 2 diabetic conditions. Our data also indicate that maneuvering through the mitochondrial function might be a viable, indirect method to modulate lymphocyte homeostasis in T2DM. PMID- 22061043 TI - Patient-specific measures of a biomarker for the generation of individual reference intervals: hemoglobin as example. AB - Although hemoglobin concentration measurement is among the most commonly performed blood tests, the description of global population parameters, heterogeneous factors, and within-subject variations in patients with disease remains incomplete. As absolute action values are being published in the medical literature and by government healthcare agencies, these measures are important to define patient-specific ranges of biomarkers. Here, a global clinical trial data set composed of 1,537,932 hemoglobin values from 416,374 patients and 372 clinical indications was generated over 2 years by automated analyzers in a global network of 5 laboratories. Within- and between-subject components of variance and the effect of factors age, gender, nationality, and clinical indication were determined using unbalanced multiway analysis of variance. Average within-subject variances differed significantly depending on the clinical indication (0.15-1.3 g(2)/dL(2)) but, nevertheless, remained significantly lower than between-subject variances. The main sources of between-subject variation were clinical indication and gender, followed by age and nationality. An adaptive Bayesian approach was then used to generate patient-specific ranges of hemoglobin for drug safety and efficacy assessment in clinical trials. The same methodology can be applied to the evaluation of any biomarker signal in translational medicine. PMID- 22061044 TI - Oxidant mechanisms in childhood obesity: the link between inflammation and oxidative stress. AB - Evidence of obesity-induced oxidative stress in adults has emerged in the past several years, and similar evidence has been demonstrated in children more recently. The reactive species of oxygen or nitrogen can chemically alter all major classes of biomolecules by modifying their structure and function. Organisms have developed mechanisms to protect biomolecules from the deleterious effects of free radicals. These include the enzymes superoxide dismutase, catalase, and glutathione peroxidase, as well as water and lipid-soluble antioxidants, such as glutathione, ascorbate (vitamin C), alpha-tocopherol (vitamin E), and beta-carotene. Obesity creates oxidant conditions that favor the development of comorbid diseases. Energy imbalances lead to the storage of excess energy in adipocytes, resulting in both hypertrophy and hyperplasia. These processes are associated with abnormalities of adipocyte function, particularly mitochondrial stress and disrupted endoplasmic reticulum function. In this sense, oxidative stress can also be induced by adipocyte associated inflammatory macrophages. There is a close link among obesity, a state of chronic low-level inflammation, and oxidative stress. In addition, the dysregulation of adipocytokines, which are secreted by adipose tissue and promoted by oxidative stress, act synergistically in obesity-related metabolic abnormalities. Adipocytokines link the local and systemic inflammation responses in the context of obesity. It is thought that the evaluation of oxidative status may allow for the identification of patients at an increased risk of complications. Decreasing the levels of chronic inflammation and oxidative stress in childhood may decrease cardiovascular morbidity and mortality in adulthood. PMID- 22061045 TI - Use of dental stem cells in regenerative dentistry: a possible alternative. PMID- 22061046 TI - Numerical analysis of micro- and nano-particle deposition in a realistic human upper airway. AB - A computational model was developed for studying the flow field and particle deposition in a human upper airway system, including: nasal cavity, nasopharynx, oropharynx, larynx and trachea. A series of coronal CT scan images of a 24 year old woman was used to construct the 3D model. The Lagrangian and Eulerian approaches were used, respectively, to find the trajectories of micro-particles and concentration of nano-particles. The total and regional deposition fractions of micro/nanoparticles were evaluated and the major hot spots for the deposition of inhaled particles were found. PMID- 22061047 TI - Evaluation of bioactive sphingolipids in 4-HPR-resistant leukemia cells. AB - BACKGROUND: N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) is a synthetic retinoid with potent pro-apoptotic activity against several types of cancer, but little is known regarding mechanisms leading to chemoresistance. Ceramide and, more recently, other sphingolipid species (e.g., dihydroceramide and dihydrosphingosine) have been implicated in 4-HPR-mediated tumor cell death. Because sphingolipid metabolism has been reported to be altered in drug-resistant tumor cells, we studied the implication of sphingolipids in acquired resistance to 4-HPR based on an acute lymphoblastic leukemia model. METHODS: CCRF-CEM cell lines resistant to 4-HPR were obtained by gradual selection. Endogenous sphingolipid profiles and in situ enzymatic activities were determined by LC/MS, and resistance to 4-HPR or to alternative treatments was measured using the XTT viability assay and annexin V-FITC/propidium iodide labeling. RESULTS: No major crossresistance was observed against other antitumoral compounds (i.e. paclitaxel, cisplatin, doxorubicin hydrochloride) or agents (i.e. ultra violet C, hydrogen peroxide) also described as sphingolipid modulators. CCRF-CEM cell lines resistant to 4-HPR exhibited a distinctive endogenous sphingolipid profile that correlated with inhibition of dihydroceramide desaturase. Cells maintained acquired resistance to 4-HPR after the removal of 4-HPR though the sphingolipid profile returned to control levels. On the other hand, combined treatment with sphingosine kinase inhibitors (unnatural (dihydro)sphingosines ((dh)Sph)) and glucosylceramide synthase inhibitor (PPMP) in the presence or absence of 4-HPR increased cellular (dh)Sph (but not ceramide) levels and were highly toxic for both parental and resistant cells. CONCLUSIONS: In the leukemia model, acquired resistance to 4-HPR is selective and persists in the absence of sphingolipid profile alteration. Therapeutically, the data demonstrate that alternative sphingolipid-modulating antitumoral strategies are suitable for both 4-HPR resistant and sensitive leukemia cells. Thus, whereas sphingolipids may not be critical for maintaining resistance to 4-HPR, manipulation of cytotoxic sphingolipids should be considered a viable approach for overcoming resistance. PMID- 22061048 TI - The effects of neuromuscular training on the gait patterns of ACL-deficient men and women. AB - BACKGROUND: Anterior cruciate ligament rupture is the most common knee ligament injury sustained by active individuals, and the relative injury risk is sex specific. Women not only demonstrate an increased risk for injury, but also a poorer response following ligament rupture. Perturbation training has shown positive results in healthy females, but gender-specific responses to training after injury have not been evaluated. The purpose of this investigation was to describe the effects of perturbation training on the gait characteristics of male and female non-copers. METHODS: Biomechanical data were collected before and after training on 12 male and nine female non-copers using standard motion analysis techniques. Subjects walked at a consistent, self-selected speed over an embedded force plate. Data from both limbs were post-processed and analyzed using a mixed model analysis of variance and minimal clinically important differences to compare the limb behaviors of men and women. FINDINGS: Prior to training, only women demonstrated significant hip joint excursion asymmetry (ES=1.03; P=0.009). Minimal clinically important difference values showed that the involved limb of the women had reduced hip and knee flexion angles and moments, truncated knee excursions, and increased hip excursions when compared to their own uninvolved limb and the limbs of the male non-copers. Following training, only knee extensor moment values exceeded the minimal clinically important differences in women. INTERPRETATION: Female non-copers demonstrated unique movement strategies following injury and perturbation training. Women may be a meaningful subgroup of non-copers, and future investigations should consider the effects of gender in the outcomes of non-copers. PMID- 22061049 TI - A Simple, rapid preparative method for isolating and purifying oxymyoglobin. AB - A simple and rapid procedure was developed to isolate and purify preparative quantities (up to 200 mg) of reduced myoglobin (98% oxy) of high purity (>96%) from beef and pork muscles. This method involved fractional precipitation of a crude myoglobin extract with ammonium sulfate and purification with a single Chromatographic step on a Sephadex G-100 column. The metmyoglobin level of the myoglobin preparation was minimised by using muscle from freshly slaughtered animals (<48h post-mortem), trimming the muscle immediately before use to remove any oxidised myoglobin on the surface and carrying out all procedures at low temperature (0-5 degrees C) and alkaline pH (8.0-8.5). The purity of the myoglobin preparations was confirmed by ion exchange HPLC and SDS-polyacrylamide gel electrophoresis. The method was effective for skeletal muscle of both low myoglobin content (pork) and high myoglobin content (beef). The resulting purified myoglobin was very stable and there was little change in metmyoglobin level or autoxidation rate during 3 months' storage at 0 degrees C. PMID- 22061050 TI - Effect of age, diet and sex on muscle energy metabolism and on related physicochemical traits in the rabbit. AB - Muscle energy metabolism and related physicochemical traits of the meat were studied in 84 Provisal hybrid rabbits of both sexes. From weaning (30 days) to 55 days of age, the rabbits were divided into 4 groups which were given ad libitum one of the following diets: H diet with high digestible energy (DE) level, L diet with low DE level, F diet with high DE level, obtained by supplementing with animal fats, and W diet with moderate DE level. The H, L and F diet were suitable for lactating does and weaning rabbits; the W diet for weaned young rabbits. From 55 days to slaughter age, the rabbits were given a G diet suitable for growing and fattening. The rabbits were slaughtered at 55 days (23 rabbits), 80 days (31 rabbits) or 87 days (30 rabbits) of age. The activity of a representative enzyme of the glycolytic (fructose-1,6-diP aldolase) and oxidative (NADP-isocitrate dehydrogenase: ICDH) energy metabolism pathways and two related physicochemical traits, namely lightness (L (*)) and ultimate pH (pH(u)), were determined in the biceps femoris (BF) and longissimus lumborum (LL) muscles. The chemical composition of whole longissimus dorsi (LD) and total hindleg (HL) muscles was also determined. In BF and LL muscles, the activity of the glycolytic energy metabolism increased during the fattening period, as a result of metabolic differentiation. The increase stopped earlier in BF than in LL muscle. Variations in pH(u) values followed the same trend. The dietary effect on biochemical and physicochemical traits was moderate. A slight decrease in muscle pH(u) was observed under the less energetic diets. Aldolase activity was significantly higher in females. The significant correlations between metabolic and physicochemical traits confirmed that as glycolytic energy metabolism increases, the protein content increases, whereas pH(u) decreases. Slaughter weight was positively correlated to glycolytic energy metabolism. PMID- 22061051 TI - Carcass composition and meat quality parameters of entire and castrate farmed blackbuck antelope (Antilope cervicapra). AB - This is the first report on the meat quality and carcass composition of farmed blackbuck antelope (Antilope cervicapra). Seventeen animals comprising entire males aged 7-10 months, entire males aged 13-16 months, and castrated males aged 13-16 months of age were raised on improved pastures, herded (one man plus a dog) into yards, transported 63 km and slaughtered in a commercial abattoir. Carcasses were Tenderstretched (hung by the pelvis allowing the hind legs to drop). Castration reduced liveweight gain but had no effect on carcass weight. All carcasses were very lean with mean separable fat ranging from 0.3% in 13-16 month entires to 3.5% in castrates of the same age. Primal cuts composition was similar for all three groups except that the castrates had a proportionately less developed neck and a proportionately heavier brisket than either group of entire males. Mean ultimate pH for each of four muscles (aged LD, unaged LD, aged ST, aged BF) from each treatment group ranged between 5.47 and 5.75. The meat was very tender, with mean Warner Bratzler initial yield values between 1.3 and 3.4 kg, and mean Warner Bratzler peak force values between 2 and 4.5kg. There was a tendency for the meat from 13-16 month entires to be leaner, have higher ultimate pH, and be slightly less tender than that of the other two groups. It was concluded that farmed blackbuck antelope can produce meat of high objective quality and that castration is useful as a management strategy. PMID- 22061052 TI - Effect of breed on the muscle glycogen content and dark cutting incidence in stressed young bulls. AB - Observations have shown relevant differences in the behaviour of Brown Swiss bulls and Pirenaico bulls. Because temperament is involved in the development of dark cutting beef (DC), the aim of this study was to investigate the influence of breed on muscle glycogen content and on the incidence of DC condition. Twenty four Brown Swiss bulls and 24 Pirenaico bulls were used. The animals were divided into a stressed group (S) and a control group (C). In group S, bulls were mixed with unfamiliar animals overnight before slaughter. In group C, bulls were slaughtered immediately after arrival at the abattoir. The results show that the glycogen concentrations in m. longissimus dorsi and m. sternomandibularis from unstressed animals were similar in both the Brown Swiss and the Pirenaico breeds. The muscle glycogen concentration was depleted in all stressed bulls, nevertheless some low concentrations were insufficient to adversely affect the meat ultimate pH value. Finally, there was no influence of breed on the incidence of the dark cutting condition. PMID- 22061053 TI - Relationship between structural properties of intramuscular connective tissue and toughness of various chicken skeletal muscles. AB - The shear-force value, the total amount of collagen, heat-solubility of collagen and thickness of the perimysium were measured on six kinds of chicken skeletal muscle. Toughness of the meat was significantly correlated with both total amount of collagen (r(2) = 0.94) and thickness of the perimysium (r(2) = 0.95). Although differences in heat-solubility of collagen were observed among the six muscles, heat-solubility of collagen was not correlated to the shearforce value. These results suggest that the total amount of collagen and structures of the perimysium are the major factors determining toughness of chicken. PMID- 22061054 TI - Effects of postmortem temperature and time on the water-holding capacity of hot boned turkey breast and thigh muscle. AB - Turkey breast and thigh muscles were excised immediately after slaughter and held from 0.25 to 4 h postmortem at 0, 12 or 30 degrees C to determine postmortem time and temperature effect on muscle pH, drip loss, sarcomere length, homogenate supernatant weight, salt-soluble protein and cooking yields. Higher temperature and longer storage time induced greater drip losses in breast. Longer storage time induced greater drip losses but the least drip loss occurred at 12 degrees C in thigh muscle. High temperature increased the supernatant weight in breast but decreased that in thigh. Storage time increased supernatant weight and supernatant salt soluble protein levels in both muscles. Homogenate cooking yields of breast containing water, salt and phosphate (HWSP) were higher for 0 and 12 degrees C compared with 30 degrees C, and increased with storage. The low postmortem temperature (0 degrees C) decreased homogenate cooking yields in thigh. These findings indicate that lower postmortem temperatures (0 and 12 degrees C) and shorter storage time (24 h) produced the greatest water-holding capacity in turkey breast muscle, whereas high and low postmortem temperatures (30 and 0 degrees C) and longer storage (168 h) produced the least water-holding capacity in raw turkey thigh muscle. PMID- 22061055 TI - Non-destructive, ultrasonic evaluation of meat quality in live Japanese Black steers from coloured images produced by a new ultrasound scanner. AB - An improved colour scanning scope was used for evaluating meat quality (marbling) of live Japanese Black steers. This equipment consisted of a small size ultrasonic probe (2 MHZ) and LCD display. Seventeen fattened Japanese Black cattle were scanned at the region of the 7th rib about one week before slaughter. A picture of the cross-sectional area of the back was obtained immediately after applying the probe and contained 15 colours representing different signal strengths. The time for each scan was 2 seconds. The picture signals were fed into a computer for rapid estimation of fat percentage of the M. longissimus thoracis. After slaughter, the fat content and chemical characteristics were determined on the M. longissimus thoracis obtained from the same rib section. The range of fat content was 7.0 to 23.7% (average 18.47%). A high correlation coefficient (r = 0.90; r.s.d. = 2.01%) was obtained between actual fat percentage of the M. longissimus thoracis and colour-scanning scope SR200 estimates based on the percentage of the weak blue dot(1) in the echo. Estimates of the subcutaneous fat thickness and the cross-sectional area of M. longissimus thoracis from the scans were in good agreement with the actual carcass measurements (r = 0.69; r.s.d=0.52 cm and r = 0.81; r.s.d. = 4.26 cm(2), respectively). These results show that the new colour scanning scope is a useful instrument for estimating meat quality (marbling) in live cattle. PMID- 22061056 TI - Detection of antimicrobial residues in poultry meat and slaughter cattle in Nigeria. AB - The European four plate test (FPT) was used to establish whether and where antimicrobial residues accumulate in the tissue of commercial poultry and slaughter cattle in Nigeria. Bacillus subtilis and Staphylococcus aureus sensitive to different antimicrobials seeded on nutrient agar media at different pH levels were employed. Inhibitory residues were detected in the muscles, liver, and/or kidney of experimental local chickens, commercial broilers and layers and 2 of 24 slaughter cattle. The public health hazards of antimicrobial residues in developing countries are discussed. PMID- 22061060 TI - Microbial growth and biochemical changes on naturally contaminated chilled-beef subcutaneous adipose tissue stored aerobically Lasta, J. A., Pensel, N., Masana, M., Ricardo Rodriguez, H. & Garcia, P. T. (1995). Meat Sci., 39(1), 149. PMID- 22061061 TI - Evolution in the shoulder composition of hairless Mexican pigs throughout the curing and drying processes. AB - The objective of this study was to analyze the chemical composition changes of the shoulders of the Hairless Mexican pigs (HMP) throughout the curing and drying processes. Shoulder composition (% of fat, protein and ash) was evaluated for moisture, water activity (Aw), pH, nitrates and sodium chloride (NaCl). Results from this study were analyzed using a descriptive analysis. Dry-curing significantly decreased Aw (raw: 0.97+/-0.01, dry-cured: 0.87+/-0.01), % of moisture (raw: 50.75+/-1.16, dry-cured: 31.43+/-1.16), pH (raw: 6.11+/-0.04, dry cured: 5.82+/-0.04), nitrates (raw: 54.26+/-3.22, dry-cured: 20.03+/-3.22) and % of ashes (raw: 10.00+/-0.41, dry-cured: 8.13+/-0.41) throughout the process. Percentage of NaCl (raw: 0.28+/-0.04, dry-cured: 0.72+/-0.04), of fat (raw: 17.46+/-1.50, dry-cured: 20.53+/-0.11) and protein (raw: 20.63+/-1.34 and dry cured: 30.21+/-0.95) increased significantly. The low percentage of salt and moisture and the high percentage of fat found on the final HMP shoulders suggested that the dry-curing produced a highly palatable product. PMID- 22061062 TI - Influence of sensory characteristics on the acceptability of dry-cured ham. AB - The influence of different sensory attributes on the acceptability of dry-cured Iberian ham was studied. Partial least squares regression analysis showed that juiciness and several flavour traits were the major attributes positively influencing acceptability of dry-cured Iberian ham, whereas yellowness of the fat, dryness and fibrousness showed a negative influence. Using stepwise multivariate regression, juiciness and flavour intensity were the two traits that better explained the acceptability of dry-cured ham, the linear model obtained showing a regression coefficient of 0.526. The regression coefficient of acceptability with juiciness and flavour intensity was higher using a piecewise linear regression model (R(2)=0.759) showing, therefore, a discontinuous relationship between these variables. However, results on product acceptability have been obtained using trained panellists and it might be possible that the use of a consumer panel would change these conclusions. PMID- 22061063 TI - Physiological and structural events post mortem of importance for drip loss in pork. AB - Early post mortem metabolism and structural changes from 3 to 24 h, together with pH, temperature and impedance Py development were investigated in 37 Duroc*Landrace*Large White (DLY) pigs covering a range of drip loss from 2.2 to 12.6%. Multivariate statistical analysis was used to assess the impacts of different metabolites, pH and temperature, impedance, cytoskeletal protein degradation and extracellular cross-sectional area on drip loss. Taken as single factors, the concentration of lactate could explain 80% of the variation in drip, inosine monophosphate (IMP) and adenosine triphosphate (ATP) concentration explained 71 and 68%, respectively, whereas inosin and glycogen levels explained only 59 and 60%. The extracellular area was found to explain 39% of the variation in drip. The area between fibres provided more significant information than did the area between fibre bundles. The degradation of the cytoskeletal proteins was not related to drip loss. Impedance Py development over 24 h could explain 66% of the variation in drip, whereas pH and temperature explained 85 and 87%, respectively. A model including all measured variables could explain 83% of the variation in drip. However, only pH, temperature, impedance, [ATP](1 h) and [lactate](1 h and 2 h) were significant in relation to drip. By reducing the variables in the multivariate analysis, 89% of the variation in drip could be explained by a model containing only pH(2 h) and temperature(1 min). To explain variation in drip loss, pH and temperature measurements at significant time points were sufficient. Variation in post-mortem metabolites did, however, explain why variation in pH and temperature occurred. Development of drip channels was ruled by pH and temperature while impedance development was highly correlated to pH. This multi-faceted study shows those parameters, which can best be used to indicate or predict WHC, as well as those indicating the basic mechanism underlying variations in drip. PMID- 22061064 TI - Meat traceability using DNA markers: application to the beef industry. AB - Consumer concerns about beef demands instruments to assure its traceability. A methodology using DNA markers is proposed for beef identification focussing on a Spanish beef certification, Ternera de Navarra (Beef of Navarra). To validate this methodology the number of markers used and the implications of population structure in individual identification were evaluated. In order to get practical implementation, the sampling levels required, depending on the number of markers and amount of possible fraud, is also discussed. Using at least eight very informative markers the origin of retailed meat is always found independent of genetic population structure. The total control of fraud would be very expensive using large-scale application of DNA analyses and a strategy based on anonymous sampling is proposed. PMID- 22061065 TI - The effect of experimental stress on sarcoplasmic reticulum Ca(2+) transport and meat quality in pig muscle. AB - Stress before slaughter affects the meat quality of pigs and a disorder in the Ca(2+) transport of the sarcoplasmic reticulum (SR) results in inferior meat quality. The object of this work was to determine the impact of stress on SR Ca(2+) transport in pig muscle in animals with no mutation in the Ca(2+) release channel. At about 80 kg live weight, pigs were stressed either by running for 4 min (n=9) or by a 5 min application of a nose snare (n=7). Immediately before and after the application of the stress, as well as 4 h after the stress, biopsy samples of the longissimus muscle were taken and the Ca(2+) uptake of the homogenised muscle samples determined. The nose snare stress reduced the rate of Ca(2+) uptake by 9% (P=0.02) and running by 18% (P=0.06). Uptake in samples taken 4 h after the stress was at initial levels. The pigs were slaughtered at an average live weight of 109 kg. Half the pigs were stressed just before slaughter for 5 min by the use of a nose snare. Immediately after exsanguination longissimus muscle samples were taken, Ca(2+) uptake measured, and later standard meat quality parameters were determined. Although the stress reduced the Ca(2+) uptake rate (61.3 vs. 46.4 nM/min per mg protein for control and stressed pigs; P=0.04), the meat quality was not significantly affected. PMID- 22061066 TI - Fatty acid composition of muscle and fat tissues of Omani Jebel Akhdar goats of different sexes and weights. AB - This paper describes the fatty acid (FA) composition of muscle and fat tissue in Omani Jebel Akhdar buck, wether and does slaughtered at 11, 18 or 28 kg body weight (BW). The fat percentage in dry matter (DM) of the subcutaneous and kidney fats ranged between 85 and 98% and that of muscle ranged between 17 and 21%. Subcutaneous fat tended to have lower DM than kidney fat. Palmitic (C16:0), stearic (C18:0) and oleic (C18:1) acids comprised the largest proportions of FA in the muscle tissue (approximately 80%) with oleic acid being the most abundant. Ninety-one percent of the total FA were contributed by the C16 and C18 fatty acids being 31.6 and 58.5%, respectively. C19 and C20 were not detected in the muscle tissue. The essential FA, C20:2, C20:3 and C20:4 contributing about 1%. Muscle tissue of the Jebel Akhdar goat contained an average 51.3% and 48.7% of saturated (SFA) and unsaturated fatty acids (UFA), respectively. Polyunsaturated FA (PUFA) constituted about 5% and monounsaturated (MFA) 43.5% of the total FA. Subcutaneous fat contained more total FA (68.08%) than kidney fat (48.14%) in the whole tissue. Kidney fat contained higher percentages of C16 and C18 but less C:18:1 than subcutaneous fat. The proportions of SFA to UFA was high in both fat depots with the SFA being much higher in the kidney than subcutaneous fats. C16, C18 and C:18:1c acids comprised 64.2 and 78% and C16s and C18s made up 81 and 85% of total FA in subcutaneous and kidney fats, respectively. In both subcutaneous and kidney fats, there was a trend of increasing values of DM and fat percentage with intact males having the lowest and females the highest values. Males had higher levels of C15, C18:2 and C18:3 but lower levels of C17, C18 and total C16, C18 and C18:1 in muscle tissue. Intact males had higher levels of C10, 12, 15 FA but lower C16:1 and C16+18+18:1 than others in subcutaneous fat. Intact males had a similar trend for C12 and 14 but lower SFA and higher UFA in kidney fat. There was a trend of increasing DM and fat% in dry matter with increasing body weight. C10, 12 and 14 of the kidney fat decreased with increasing slaughter weight. There was a trend of the two C16 FA decreasing and the four C18 increasing with BW in the kidney fat. This resulted in proportions of the total C16 and C18 FA increasing from 81.8 to 86.8%. These findings confirm those of other studies on goat meat quality that, as judged by fatty acid composition it is not inferior to that of meats from other farm animals. PMID- 22061067 TI - Influence of vitamin E on lipid and protein oxidation induced by H(2)O(2) activated MetMb in microsomal membranes from turkey muscle. AB - Lipid and protein oxidation generated by metmyoglobin+H(2)O(2) were studied in microsomal membranes of turkey muscles. With a basal diet enriched with 6% soya oil and supplemented with vitamin E (30 ppm for control and 400 ppm for supplemented animals) oxidations were investigated by different methods. Lipid oxidation was estimated by TBARS and lipofuscins measurement and protein oxidation was measured by an estimation of carbonyl groups and free thiols. Supplementation of turkeys with alpha-tocopheryl acetate increased the vitamin E content of microsomal membranes and had a protective (and significant) effect on lipid oxidation when measured by the two techniques. Vitamin E supplementation significantly protected free thiols from oxidation but had only a small effect (non significant) on carbonyl group formation. No vitamin E dietary supplementation effect was observed on radical formation, as measured by optical and ESR spectroscopy. PMID- 22061068 TI - Effect of fat level and partial replacement of pork backfat with olive oil on processing and quality characteristics of fermented sausages. AB - Six formulations of dry fermented sausages were produced in three replications with three initial fat levels (30, 20 and 10%) and two levels (0 and 20%) of pork backfat replacing olive oil. After 4 weeks of fermentation and ripening the fat content of the treatments with 30, 20 and 10% fat level ranged from 38.86 to 43.60%, 25.56 to 26.86% and 19.01 to 20.14%, respectively. Fat level affected (P<0.05) the weight losses, the chemical composition, the Gram -ve bacterial count, the lightness, the texture and the appearance of fermented sausages. Replacing 20% of pork backfat by olive oil affected (P<0.05) the lightness and yellowness of sausages. Fat-reduced sausages without olive oil and low-fat sausages with olive oil had the highest score for odour and taste. However, the appearance of fat-reduced sausages was just acceptable while that of low-fat sausages was unacceptable, because the surface was intensively wrinkled and case hardening had developed. Further research is needed to improve the appearance of these sausages. PMID- 22061069 TI - Chloride salt type/ionic strength, muscle site and refrigeration effects on antioxidant enzymes and lipid oxidation in pork. AB - The effects of NaCl and KCl at varying ionic strengths on catalase and glutathione peroxidase (GSH-Px) activities and lipid oxidation in refrigerated ground pork muscles from different anatomical locations were studied. Catalase and GSH-Px activities were higher in boston butt (BB) than in longissimus dorsi (LD), whereas lipid oxidation measured by 2-thiobarbituric acid substances (TBARS) content was higher in LD. Catalase activity was stable in both BB and LD during 4-day storage; GSH-Px activity decreased in LD. GSH-Px activity decreased more with NaCl than KCl, whereas salt type had no consistent effect on catalase activity. TBARS content, however, increased more with NaCl than with KCl. NaCl at the highest ionic strength decreased GSH-Px activity by 19.2 and 18% in LD and BB, respectively, and increased TBARS content by 8- and 3.6-fold. Results indicated that pork samples with higher catalase and GSH-Px activities would undergo less lipid oxidation, and the accelerated lipid oxidation in salted pork may be partly related to a decrease in GSH-Px activity. PMID- 22061070 TI - The relationship between post-mortem calcium concentration or pH and indicators of proteolysis in ovine muscle. AB - The relationship between post-mortem calcium concentration in muscle and indicators of proteolysis was examined and compared with pH as a predictor of these changes. Muscle samples (m. longissimus et thoracis lumborum; LTL) were obtained from the left side of 24 lamb carcasses at pH 6.2 and 6.0 and then at 1 and 2 days post-mortem (n=96). Alternate carcasses were electrically stimulated (low voltage) within 15 min of death. The myofibrillar fragmentation index (MFI) was determined on samples taken at pH 6.2 and 1 and 2 days post-mortem (n=72). Protein solubility, pH and free calcium concentration were measured on all samples (n=96). The post-mortem degradation of myofibrillar proteins was followed using SDS electrophoresis on all samples (n=96) from which the relative amounts of the 30 kDa fragment and a protein designated M1 were quantified. Transformation of data values for each variable (MFI, protein solubility, 30 kDa fragment and protein M1) improved the normality of the residuals and increased the variance explained by either calcium concentration or pH. pH was a better predictor of MFI and the 30-kDa fragment than calcium concentration and this was reversed when protein solubility and the protein designated M1 was predicted. Of the variables protein solubility could be predicted with the greatest accuracy using calcium concentration (R(2)=0.64; R.S.D.=0.81) or pH (R(2)=0.60; R.S.D.=0.85). However overall calcium concentration was not superior to pH as a predictor of the changes in the different indicators of proteolysis examined in this study. PMID- 22061071 TI - Changes in immunoelectron microscopic localization of cathepsin D in muscle induced by conditioning or high-pressure treatment. AB - Changes in the localization of cathepsin D in postmortem and pressurized rabbit muscles were investigated by immunoelectron microscopy. The anti-cathepsin D monoclonal antibody strongly labeled a large vesicle in a subsarcolemmal part of the cell , which strongly suggests that this is the primary lysosome. The liberation of the cathepsin D entrapped in the lysosomes in the muscle prepared immediately after death proceeded with the progress of the conditioning. The release of almost all cathepsin D from the lysosomes and its absorption on the myofibrils were observed in the muscle conditioned for 14 days. The accumulation of lysosomes having various volumes and shapes accompanied with the disruption of myofibrillar structure was also observed. The liberation of cathepsin D from the lysosomes can be attributed to the modification of membranes permeability of the lysosomes during conditioning. When the muscle was pressurized at 100 MPa, the modification of the round shape of the lysosome was observed. With the increase of the pressure applied to the muscle, the release of cathepsin D from the lysosome due to the disruption of membrane was accelerated, and absorption of the released cathepsin D on the myofibrils was observed. From the results obtained, it was clear that the changes in the localization of cathepsin D accompanied with the modification of lysosomes induced by the brief exposure to high pressure were drastic in comparison with that in the muscle during conditioning. PMID- 22061072 TI - Effects of pH and temperature on metmyoglobin solubility in a model system. AB - From a series of experiments heating metmyoglobin solutions at pH 5.0 through 7.0, the effects of temperature and pH on the thermal stability of metmyoglobin were investigated. The percent metmyoglobin denatured at temperatures from 25 to 80 degrees C was determined. pHs lower than 6.5 caused metmyoglobin denaturation at various temperatures from 25 to 80 degrees C, but it was particularly apparent when pH was < 5.6. Thermal stability of metmyoglobin increased as pH increased. Metmyoglobin denaturation occurred at 55 degrees C at pH 5, however, denaturation did not occur until 60 degrees C at pHs from 5.3 to 7.0. A slower heating rate (0.9 degrees C/min) resulted in more metmyoglobin thermal denaturation than a faster heating rate (1.3 degrees C/min) when the temperature was above 55 to 60 degrees C. The denaturation caused by low pH alone was reversible, while that caused by high temperature was not. Techniques which increase muscle pH, such as the injection of sodium bicarbonate, could effectively improve the color condition of PSE meat. PMID- 22061073 TI - Effect of transport time on welfare and meat quality in pigs. AB - The purpose of this study was to determine the effects of transport duration on some welfare and meat quality parameters. For the study 144 pigs were used. One group of 72 animals was subjected to 15 min and the others to 3 h transport time. Blood from all animals was analysed in order to detect stress-susceptible pigs and assess pre-slaughter stress. Meat quality parameters were analysed from Longissimus thoracis and Semimembranosus muscles. It was concluded that under normal Spanish commercial conditions, pigs subjected to short transport showed a more intense stress response and poorer meat quality than pigs subjected to moderately long transport when they were immediately slaughtered on arrival at the slaughterhouse. Transport of 3 h might have allowed the animals to adapt to transport conditions and then could act as a resting period like a lairage time. The effect of transport time on welfare and meat quality parameters was more important than genotype and sex. Nevertheless, from the point of view of blood enzyme activities, genetically stress susceptible females transported for 3 h were more sensitive to muscle damage. PMID- 22061074 TI - Characterisation and screening for antimicrobial substances of slaughtered cattle in Zaria, Nigeria. AB - The occurrence of antimicrobial drug residues in 500 routinely slaughtered cattle in Zaria, Nigeria, was determined. A microbial inhibition test with Micrococcus luteus ATCC9341 was used to test urine at the time of slaughter for the presence of antimicrobial substances. Thirty-seven (7.4%) of the urine samples were positive for antimicrobial substances. Positive cases were not distributed according to breed (P>0.05), but occurred significantly more in male cattle aged 3-9 years and in those with good body condition score (P<0.05). Thirty-eight cases, in the form of 16 different pathological conditions, were seen from visual inspection of carcasses. Lymphadenopathy was seen in 10 (23.7%) carcasses including one antimicrobial substances positive carcass. Dermatophilosis and emaciation constituted 15.8 and 13.2% of pathological conditions observed, respectively. PMID- 22061075 TI - Effect of Brussels sprouts and inulin/rape seed cake on the sensory profile of pork M. longissimus dorsi. AB - The objective of the present study was to evaluate the influence of two diets containing either Brussels sprouts or inulin/rape seed cake, compared with a standard diet (control) for slaughter pigs on flavour and odour attributes and sensory profile of cooked pork. Three weeks prior to slaughter 24 female pigs were allocated to three diets: (1) a standard grower-finishing diet (control) for slaughter pigs containing barley, wheat and soy-bean meal, (2) the control diet containing 11 energy percent Brussels sprouts and (3) a diet containing 25% inulin and 55% rape seed cake. The odour and flavour of the cooked meat from inulin/rape seed cake-fed pigs differed significantly from the other two diets, showing reduced meat odour, increased pig and acrid odour, increased pig flavour, reduced fresh flavour and total impression. Meat from the Brussels sprouts-fed pigs deviated only slightly from the control-fed pigs. PMID- 22061076 TI - Inhibition of Listeria monocytogenes by a bacteriocinogenic Lactobacillus sake strain in modified atmosphere-packaged Brazilian sausage. AB - Lactobacillus sake 2a is a bacteriocinogenic strain isolated from "linguica frescal", a Brazilian sausage. The combined effect of modified-atmosphere (MA) packaging (100% CO(2) and 50% CO(2)/50% N(2)) and addition of L. sake 2a on inhibition of growth of Listeria monocytogenes was evaluated in "linguica" stored at 6 degrees C. By the end of the first week, the inhibition of L. monocytogenes due to MA was significant (P?0.05) while the presence of L. sake 2a did not influence significantly the growth of the pathogen. After 14 days, a reduction of 1.3-1.4 log in counts of L. monocytogenes was observed in samples containing L. sake 2a only or MA packaged only, while a reduction of 3.5 log was detected in those submitted to both treatments. Results indicate that inhibition of L. monocytogenes in "linguica frescal" by the bacteriocinogenic L. sake 2a is enhanced by the packaging of the product in MA. PMID- 22061077 TI - Randomised clinical trial: the efficacy of prucalopride in patients with chronic intestinal pseudo-obstruction--a double-blind, placebo-controlled, cross-over, multiple n = 1 study. AB - BACKGROUND: Chronic intestinal pseudo-obstruction is a disabling condition for which there are no established drug therapies. The condition is caused by a diverse range of intestinal myopathies and neuropathies. AIM: To assess the therapeutic efficacy of prucalopride, a selective high-affinity 5-HT(4) receptor agonist, we employed a multiple n = 1 study design. Each patient acted as his/her own control, each day counting as one treatment episode, allowing comparison of 168 days on each of active drug and placebo. METHODS: Double-blind, randomised, placebo-controlled, cross-over trial of four 12-week treatment periods, with 2-4 mg prucalopride or placebo daily. In each of the first and second 6 months there was a prucalopride and a placebo treatment. Patients with proven chronic intestinal pseudo-obstruction, including dilated gut, were included. Evaluation was by patient diary and global evaluation. RESULTS: Seven patients participated (mean 42 years, five female, median symptom duration 11 years). Three discontinued, two due to study length, and one on prucalopride due to unrelated malnutrition and bronchopneumonia. Four patients (three visceral myopathy and one visceral neuropathy) completed the study; prucalopride significantly improved pain in three of four patients, nausea in two, vomiting in one, bloating in four and analgesic intake. Bowel function was not changed substantially. CONCLUSIONS: n = 1 studies in rare conditions allow drug efficacy assessment. Prucalopride relieves symptoms in selected patients with chronic pseudo-obstruction. PMID- 22061078 TI - Spatial and temporal variations of urban litter in Mar del Plata, the major coastal city of Argentina. AB - Urban littering is considered an important environmental and public issue globally. This problem is growing considerably within coastal communities of the southern region of South America. The goals of this study were to assess (1) the abundance and composition of urban litter; (2) the spatial and temporal variations of its abundance; and (3) the relationship between the abundance of litter and three anthropogenic variables (i.e. abundance of pedestrians, of parked vehicles, and of trash bins) in Mar del Plata, the most populated coastal city in Argentina. Eighty-eight transects, each covering 1425 m(2), were sampled along four sites from April 2008 to March 2009. Results showed 20,336 items (ca. 14 items per m(2)) of which cigarette butts (33%), papers (31%), and plastics (22%) were the most commonly littered items. Higher amounts of litter were found in an industrial area (city's harbor), while the abundance of litter appeared relatively even throughout the year. Redundancy analysis techniques indicated a high abundance of all three anthropogenic variables associated with the central business district area of the city and an area in close proximity to a major seaside resort, where cigarette butts and papers dominated. This is the first study that has examined spatial and temporal variations of urban litter in a high density coastal city in Argentina. Our results showed that addressing the problems associated with urban litter must include intensive educational and advertising campaigns directed at pedestrians and owners of parked vehicles, but waste reduction, clean-up operations and law enforcement should be also considered. PMID- 22061079 TI - Fatty acid composition and eating quality of lamb types derived from four diverse breed * production systems. AB - Carcass composition, muscle fatty acids and eating quality of loin chops were examined in ram lambs from four diverse breed * production system groups: pure Welsh Mountain off upland flora, pure Soays off lowland grass, Suffolk crosses off lowland grass and Suffolk crosses off concentrates. The two Suffolk groups had heavier and better muscled carcasses than the others and Soays were particularly lean. Fatty acid composition was different between the groups. The forage-fed lambs all had high concentrations of n-3 polyunsaturated fatty acids (PUFA) including 18:3 (alpha-linolenic acid) and 20:5 (eicosapentaenoic acid) compared with Suffolks-concentrates which had high concentrations of the n-6 PUFA 18:2 (linoleic acid) and 20:4 (arachidonic acid). Soays were high in both n-3 and n-6 PUFA. Flavour characteristics in grilled chops were similar in Welsh Mountain and Suffolks-grass which differed from Soays and Suffolks-concentrates. The latter two groups had low scores for lamb flavour and overall liking and high scores for abnormal lamb flavour, metallic, bitter, stale, and rancid. Soays had the highest score for livery. These results extend previous findings of the association between feed, PUFA composition and lamb flavour profile and confirm that forage-fed lamb is preferred by UK taste panellists. They also identify a specific breed effect on the quality of meat from lambs raised on forage. These findings suggest that possibilities exist for the production of meat with specific quality characteristics. PMID- 22061080 TI - The effects of diet and breed on the volatile compounds of cooked lamb. AB - The effect of varying the n-3 polyunsaturated fatty acid (PUFA) composition of lamb muscle on the formation of aroma volatiles during cooking has been examined. The meat was obtained from four groups of Suffolk and Soay lambs fed different supplementary fats: a palm-oil based control; bruised whole linseed, which increased muscle levels of alpha-linolenic acid (C18:3 n-3); fish oil, which increased eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3); and equal quantities of linseed and fish oil (fat basis). Higher quantities of lipid oxidation products were found in the aroma volatiles of lamb muscle from animals fed fish oil, compared to the control. In particular, unsaturated aldehydes, unsaturated hydrocarbons and alkylfurans increased up to fourfold. These compounds derived from the autoxidation of PUFAs during cooking. Although some of these volatiles were increased in meat from animals fed the linseed supplement, the effect was not as great as with the fish oil fed lambs. Levels of volatiles derived from the Maillard reaction, such as pyrazines and sulfur compounds, were up to four times higher in Soays than Suffolks. PMID- 22061081 TI - Meat starters have individual requirements for Mn(2+). AB - The effect of different Mn(2+) concentrations on sausage fermentation was evaluated. A screening experiment was carried out with six lactobacilli starters in a sausage model. To further investigate the effects found, two selected lactobacilli strains were tested in pilot-scale sausage production. For all starters an increased fermentation rate was observed after Mn(2+) addition. Differences in the development of microbial, textural and sensory parameters were observed in the sausages. For one of the cultures these differences levelled out during sausage production yielding identical end products with and without Mn(2+), for the other strain the differences due to Mn(2+) addition in the sausages remained throughout the production process yielding sausages with different properties. Knowing a starter culture's requirements for Mn(2+) will allow optimisation of dry fermented sausage production in order to increase reliability and reproducibility of production decrease fermentation time and ensure microbial safety of the final product. PMID- 22061082 TI - Oxidative stability of lipids and cholesterol in salame Milano, coppa and Parma ham: dietary supplementation with vitamin E and oleic acid. AB - An investigation has been carried out on the effect of dietary supplementation with vitamin E and oleic acid on oxidative stability of Italian representative pork products. Fatty acid composition of deposited fat was modified in the oil supplemented groups with negative effects on fat firmness. Oil supplementation significantly increased vitamin E content of muscles, as well. Oxidative stability of fat, evaluated by TBARS and cholesterol oxides, has not shown significant differences between dietary treatments but, although the differences were not significant, the tendency was sufficiently clear, especially in salame Milano, towards a lower oxidation level in vitamin E enriched meat. Cholesterol oxidation was found to vary in general around 0.1% of total cholesterol and the only cholesterol oxides observed were 7beta-hydroxycholesterol, 5,6alpha epoxycholesterol and 7-ketocholesterol. Aldehydes content and distribution appeared to be linked, firstly, to the specific processing technology of the product and, secondly, to the changed fatty acid composition. PMID- 22061083 TI - Prediction of water-holding capacity and composition of porcine meat by comparative spectroscopy. AB - Four spectroscopic instruments, a fibre optical probe (FOP), a visual (VIS) and near infrared (NIR) reflectance spectrophotometer, a reflectance spectrofluorometer and a low-field (1)H nuclear magnetic resonance (LF-NMR) instrument were used to perform measurements on two muscles (longissimus dorsi and semitendinosous) from 39 pigs, 18 of which were carriers of the Halothane gene. Water-holding capacity (drip loss and filter paper wetness) and chemical composition (intramuscular fat and water) of the muscle samples were determined for spectroscopic calibration. Prediction models were established by partial least squares regression to evaluate the potential of using the spectroscopic techniques in an on-line slaughterhouse system. VIS data gave good prediction models, indicating that current industrial colour systems can be advanced into more specific meat evaluation systems by including the entire visible spectral range. The FOP and fluorescence measurements were less successful, and suffered from sampling problems since they measure only a small area. The best regression models were obtained from LF-NMR data for all reference quality measures and yielded a correlation coefficient of 0.75 with drip loss. LF-NMR proved able to distinguish between the two muscles and the results for their longitudinal relaxation times, T(21), were proportional to their average myofibrillar cross sectional areas reported in the literature. PMID- 22061084 TI - Genotype with nutrition interaction on fatty acid composition of intramuscular fat and the relationship with flavour of pig meat. AB - The effects of genotype, diet and the genotype with diet interaction on fatty acid composition of neutral lipid and phospholipid of intramuscular fat in pigs were examined. Pigs from four selection lines and a control line were fed isoenergetic diets, which differed in ileal digestible lysine:digestible energy (A: 0.40, C: 0.76 and E: 1.12 g lysine/MJ DE). The selected lines resulted from seven generations of selection for high daily food intake (DFI), lean food conversion ratio (LFC) and lean growth rate on ad-libitum (LGA) or restricted feeding regimes in a Large White population. During performance test, from 30 to 90 kg, pigs were fed on either ad-libitum or restricted (0.75 g/g ad-libitum daily food intake) feeding regimes. A trained sensory panel assessed intensities of pork flavour and abnormal flavour and the hedonic characteristics of flavour liking and overall acceptability. The proportion of neutral lipid in the LGA line was lower (0.64 v 0.75, s.e.d. 0.03) while the polyunsaturated:saturated (P:S) ratio of the LFC line (0.53 v 0.41, s.e.d. 0.05) was higher than the control line and other selection lines. The DFI line had a higher phospholipid n-6:n-3 ratio than other selection lines (14 v 11, s.e.d. 1.0). Diets C and E resulted in lower neutral lipid:phospholipid ratio (0.7 v 0.8, s.e.d. 0.01), n-6:n-3 ratios for both neutral lipid (5 v 13, s.e.d. 0.8) and phospholipids (7 v 20, s.e.d. 0.6) and a higher P:S ratio (0.5 v 0.3, s.e.d. 0.03) for neutral lipid than diet A. Neutral lipid fatty acids C18:2 n-6, C18:3 n-3, C20:3 n-6, C20:4 n-6, C20:5 n-3, C22:5 n-3 and C22:6 n-3 were negatively correlated with pork flavour (-0.30, s.e.d. 0.10), flavour liking (-0.33) and overall acceptability (-0.30). In contrast, the fatty acids C16:1, C18:1 omega9 and C18:1 omega11 were positively correlated with pork flavour (0.36), flavour liking (0.39) and overall acceptability (0.40). However, correlations for fatty acids in the phospholipid class were positive for C18:2 n-6, C20:4 n-6 and C22:4 n-6 with pork flavour (0.33), flavour liking (0.23) and overall acceptability (0.23). The proportion of neutral lipid had non-significant correlations with flavour traits; pork flavour (0.01), abnormal flavour (0.08), flavour liking (-0.03) and overall acceptability (0.03). The selection lines responded in a similar manner to the different diets, such that there was little evidence for genotype with nutrition interactions for fatty acid concentrations of neutral lipids and phospholipids. Selection for high lean growth will reduce intramuscular fat, but the increased relative amount of phospholipid and concentration of polyunsaturated fatty acids are unlikely to reduce eating quality. Nutritional effects on intramuscular fat characteristics were greater than genetic effects, such that nutritional approaches to feeding pigs will provide effective methods of reducing the n-6:n-3 fatty acid ratio of human dietary fat from pigmeat and improving human health. PMID- 22061085 TI - Tenderization of wether lambs meat through pre-rigor infusion of calcium ions. AB - A study involving 36 wether lamb carcasses was conducted in order to evaluate the effects of 0.3 M CaCl(2) injection on final tenderness in muscle Longissimus thoracis et lumborum. Injection of wether lamb carcasses with CaCl(2) accelerated the post mortem tenderization process. Both control and distilled water injected animals had similar Ca(2+)-dependent proteases (MU-calpain and m-calpain) and their inhibitor (calpastatin) activities, whereas these were all significantly decreased in CaCl(2) injected animals. The effect of CaCl(2) injection on tenderness was recorded by measuring shear force values 2 and 6 days post mortem. Tenderness was significantly improved by CaCl(2) injection at both at 2 and 6 days post mortem. It was concluded that activation of MU-calpain and m-calpain was responsible for the observed post mortem proteolysis and tenderization. PMID- 22061086 TI - Feeding linseed to increase the n-3 PUFA of pork: fatty acid composition of muscle, adipose tissue, liver and sausages. AB - Eighty pigs, male and female littermate pairs, were fed a control or a test diet from 25 to 95 kg live weight. The diets, as fed, contained 15.5 g/kg linoleic acid (18:2) and 1.9 g/kg alpha-linolenic acid (18:3) (control) or 10 g/kg linoleic acid and 4 g/kg alpha-linolenic acid (test). The test diet, with added linseed, was, therefore, high in the main n-3 polyunsaturated fatty acid (PUFA) 18:3 and low in the main n-6 PUFA 18:2. Making this relatively small change led to a 56% increase in the content of 18:3 in muscle and major increases in the contents of the beneficial longer chain PUFAs EPA (20:5n-3) (100% increase) and DHA (22:6n-3) (35% increase) which are synthesised from 18:3n-3. Levels of EPA and DHA in pigmeat adipose tissue were also increased by the test diet. In liver, the test diet resulted in an 18:3 level 4* higher than in muscle, with 10* more EPA and 20* more DHA. Sausages, analysed after 6 months frozen storage also had high n-3 PUFA levels, due to the contribution of these fatty acids from both muscle and adipose tissue. From a health perspective these results confirm the potential of pigmeat to supply valuable n-3 PUFA to the human diet. The test diet produced a PUFA:saturated FA ratio in muscle of 0.4, close to the minimum recommended value for the diet as a whole and an n-6:n-3 ratio of 5, a significant improvement on the current average for pigmeat (7). It is estimated that the test diet would provide 12 g of long chain n-3 PUFA to the human diet per annum at current pigmeat consumption levels in the UK, about a third of that from oily fish. PMID- 22061087 TI - Shelf life and quality of pork and pork products with raised n-3 PUFA. AB - Pork chops, liver, bacon and sausages from 80 pigs fed on a control or a linseed rich test diet were assessed for their sensory qualities and oxidative stability after conditioning and storage, either frozen or under simulated retail display. There was no significant effect of diet on lipid oxidation as assessed by the TBA test (P>0.05) for pork, liver and sausages, values being less than 0.2 throughout the display period, lower than the threshold of 0.5 mg MDA/kg at which consumers may detect rancidity. Nor was there any significant effect of diet on colour changes of pork chops, sausages and bacon under simulated retail display conditions. Grilled loin chops, bacon and sausages from male pigs received significantly higher abnormal flavour scores than those from females but panellists were unable to discern any major differences between control and test diets, even though they could detect this relatively small sex effect. The test diet resulted in higher alpha-linolenic acid (18:3) levels, with major increases in total n-3 PUFA content, but the concentrations were generally lower than reported values that have resulted in stability problems. The n-6 PUFA content was also reduced by the test diet. The results demonstrate that the nutritional value of pigmeat can be improved by using an 18:3-enriched diet without adversely affecting normal eating quality parameters. PMID- 22061088 TI - Recovery of proteins from beef bone and the functionality of these proteins in sausage batters. AB - Four solutions [4% sodium chloride (control), 4% sodium chloride with 0.3% sodium tripolyphosphate (STP), 0.3% tetrasodium pyrophosphate (TTP) or 0.05 M sodium hydroxide (NaOH)] were used to extract proteins from beef bones. Three bone solution ratios (1:1, 1:4 or 1:10), three bone types [vertebra (lumbar), rib (4 7) and leg (femur)] and two methods of protein recovery from the extraction slurries [dialysis against 0.03 M potassium phosphate buffer (pH 5.3) and acid precipitation] were evaluated. Solutions containing phosphates or NaOH were more effective in extracting protein than sodium chloride alone. Total protein recovery was highest from vertebra bones while extraction of proteins from leg bones resulted in the lowest recovery. A solution to bone ratio of 1 to 10 recovered more total protein from vertebra or rib bones than leg bones. Dialysis recovered more total protein from extraction solutions when the protein concentration was low. Acid precipitation, however, worked best if the protein concentration in the extraction solution was high. Extraction procedures resulted in some myosin degradation. Proteins extracted from beef bone materials and recovered by dialysis, performed equally as well as other commercially available proteins when added to a finely comminuted sausage product. PMID- 22061089 TI - Effects of animal and muscle characteristics on collagen and consequences for ham production. AB - The effect of biological and technological factors on ham production were studied by analyzing collagen pyridinoline cross-linking and the thermal stability of type I collagen. The type of muscle affected hydroxylysylpyridinoline (P>0.01) and lysylpyridinoline (P<0.001) cross-linking, total intramuscular collagen concentration (P<0.0001), and the slope of type I collagen solubility as a function of time. pH (P<0.05) and genetic line (P<0.0001) affected lysylpyridinoline cross-linking. In ham production, muscle type, pH(24), nitrite salt concentration and pasteurization value affected type I collagen solubility (P<0.0001). There was a relationship between pyridinoline cross-linking and soluble type I collagen levels and between technological yield and soluble type I collagen concentration (P<0.0001). There was also a relationship between collagen pyridinoline cross-linking and technological yield if the nitrite salt (1.5%) and pH(24) (<5.55) were kept constant. Thus collagen solubility and pyridinoline content are two indicators of meat quality in ham production. PMID- 22061090 TI - Seasonal effects on Ca(2+) transport of sarcoplasmic reticulum and on meat quality of pigs with different malignant hyperthermia status. AB - The intracellular Ca(2+) concentration is mainly regulated by the sarcoplasmic reticulum (SR). A disturbed regulation leads to an increased metabolism and ultimately to inferior meat quality. In this study, pigs with normal and mutated calcium release channels (referred to as MHR and MHS, respectively) were used. One batch of pigs was slaughtered in winter months and another in summer months. The intention was to elucidate the impact of season on the Ca(2+) transport of SR and on meat quality in dependence of the MH-status. The results show an impact of MH-status and of season on the meat quality with inferior values in summer months, and in MHS pigs. Immediately after slaughter the rate of Ca(2+) sequestration of the SR with biochemically closed and with opened calcium release channels (CRC) was not different between experimental groups. However, with basic CRC (not biochemically manipulated) the Ca(2+) uptake rate of MHR muscle of summer pigs was significantly reduced and at the level of that of MHS pigs. The results indicate an impact of summer season on the ability of SR to regulate Ca(2+) concentration properly even in pigs with a normal CRC. This disturbed Ca(2+) regulation is correlated with diminished meat quality. PMID- 22061091 TI - Prediction of the soluble myoglobin content of cooked burgers. AB - The time-temperature profiles for cooking in-house made beef and lamb burgers were determined using a thermocouple placed in the centre of the burger. From these data the soluble myoglobin remaining in the burger was predicted using kinetic data from previously reported model experiments. First order kinetics were assumed for the denaturation of the myoglobin. A good correlation between observed and predicted data was observed. Thus the "degree of doneness"of different meats can be predicted when cooked under specified conditions. PMID- 22061092 TI - Processing and nutritional characteristics of value added ostrich products. AB - Two types of processed products, chopped hams (0.15% and 0.30% phosphate on final yield) and viennas (27 and 32% fat extension) were manufactured from ostrich fan fillets (M. iliofibularis) to determine the suitability of ostrich meat for processing purposes. Cooking losses differed significantly (P<0.10) between the two types of ham-like products (0.15% phosphate=1.59 and 0.30% phosphate=0.78%), indicating that an increase in phosphate addition reduced cooking loss. Cooking losses did not differ (P>0.10) between the two types of ostrich viennas. Colour evaluation (L (*),a (*),b (*)) of the fresh ostrich meat and processed ostrich products (chopped hams and viennas) indicated significant differences between the different types of viennas. Chemical composition (moisture, ash, protein and fat content) of the ostrich meat, processed ostrich products and similar types of commercially available products suggested that processed ostrich products can be formulated to compete successfully with similar types of products derived from other meat species. PMID- 22061093 TI - Autoantibodies against apolipoprotein A-1 and phosphorylcholine for diagnosis of non-ST-segment elevation myocardial infarction. AB - OBJECTIVES: To explore the diagnostic accuracies of anti-apolipoproteinA-1 (anti ApoA-1) IgG and anti-phosphorylcholine (anti-PC) IgM alone, expressed as a ratio (anti-ApoA-1 IgG/anti-PC IgM), and combined with the Thrombolysis In Myocardial Infarction (TIMI) score for non-ST-segment elevation myocardial infarction (NSTEMI) (NSTEMI-TIMI score) to create a new diagnostic algorithm - the Clinical Autoantibody Ratio (CABR) score - for the diagnosis of NSTEMI and subsequent cardiac troponin I (cTnI) elevation in patients with acute chest pain (ACP). METHODS: In this single-centre prospective study, 138 patients presented at the emergency department with ACP without ST-segment elevation myocardial infarction. Anti-ApoA-1 IgG and anti-PC IgM were assessed by enzyme-linked immunosorbent assay on admission. Post hoc determination of the CABR score cut-off was performed by receiver operating characteristics analyses. RESULTS: The adjudicated final diagnosis was NSTEMI in 17% (24/138) of patients. Both autoantibodies alone were found to be significant predictors of NSTEMI diagnosis, but the CABR score had the best diagnostic accuracy [area under the curve (AUC): 0.88; 95% confidence interval (CI): 0.82-0.95]. At the optimal cut-off of 3.3, the CABR score negative predictive value (NPV) was 97% (95% CI: 90-99). Logistic regression analysis showed that a CABR score >3.3 increased the risk of subsequent NSTEMI diagnosis 19-fold (odds ratio: 18.7; 95% CI: 5.2-67.3). For subsequent cTnI positivity, only anti-ApoA-1 IgG and CABR score displayed adequate predictive accuracies with AUCs of 0.80 (95% CI: 0.68-0.91) and 0.82 (95% CI: 0.70-0.94), respectively; the NPVs were 95% (95% CI: 90-98) and 99% (95% CI: 94-100), respectively. CONCLUSION: The CABR score, derived from adding the anti-ApoA-1 IgG/anti-PC IgM ratio to the NSTEMI-TIMI score, could be a useful measure to rule out NSTEMI in patients presenting with ACP at the emergency department without electrocardiographic changes. PMID- 22061094 TI - ESR1 in myocardial infarction. AB - Women live longer than men; this can be attributed in part to the function of estrogens. In premenopausal women 17beta-estradiol (E2) is produced mainly by the ovaries. Extra-ovarian sources of this hormone comprise adipose tissue, breast tissue, bone, leukocytes, heart, testes, prostate, adrenal tissues, and some brain structures. E2 exerts the majority of its biological functions by interacting with the nuclear receptors ERalpha and ERbeta, encoded by the ESR1 and ESR2 genes, respectively. The genomic mechanism of ER action is the regulation of the activity of target genes. In addition, E2 induces rapid cellular effects in transcription-independent, non-genomic mechanisms, acting via receptors localized in the plasma membrane, in the cytoplasm, and in the mitochondria. Notably, ERalpha commonly serves as an extra-nuclear receptor of E2. In wild type animal models of cardiac ischemia ERalpha activation reduces infarct size, apoptosis of cardiomyocytes, inflammation, and oxidative stress, induces vasodilatation and increases neovascularization. The cardioprotective role of ERalpha in human is not fully elucidated. An individual with disruptive ESR1 mutation had dysfunctional epithelium and suffered from early cardiovascular disease. An association of the common ESR1 -397T>C and -351A>G polymorphisms and of other polymorphisms with cardiovascular disease and with myocardial infarction is still not firmly established. PMID- 22061095 TI - Can sharing experiences in groups reduce the burden of living with diabetes, regardless of glycaemic control? AB - AIMS: To test whether patients with Type 1 diabetes would join support groups and benefit by improving psychosocial functioning, regardless of their HbA1c levels. METHODS: A pre-post test with follow-up after 6 and 12 months was conducted as a concurrent mixed-method study. The convenience sample included patients with Type 1 diabetes aged >=21 years, having been diagnosed >=1 year earlier. Primary outcome was diabetes-related distress (using the Problem Areas in Diabetes scale). Secondary outcomes were psychological distress and depressive symptoms (Symptom Check List -90-R/Global Severity Index and depression subscale), well being (World Health Organization 5) and HbA1c . RESULTS: Equal numbers of patients with HbA1c above and below 64 mmol/mol (8%) joined the support groups (n = 54). Focus group interviews revealed that major benefits were feeling less alone and being intuitively understood among peers. The patients perceived the support groups as a safe environment for sharing experiences. Problem Areas in Diabetes, Global Severity Index and depression subscale scores were significantly reduced post-intervention and maintained at 1-year follow-up. Well-being increased insignificantly. HbA1c was unchanged. CONCLUSIONS: Support groups are able to reduce diabetes-related and psychological distress 1 year after the intervention for patients with both good and poor glycaemic control displaying high levels of distress. Although patients with severely high levels of diabetes related distress might need more extensive therapeutic interventions to further reduce their level of distress. Further, interventions that target specific self management problems are needed for patients with poor glycaemic control to help them accomplish lower levels of HbA1c. Moreover, healthcare providers must be aware that patients with good glycaemic control might have an unacknowledged psychosocial burden of living with the illness. PMID- 22061096 TI - Lipolytic and oxidative changes in 'Chorizo' during ripening. AB - Changes in fats during the ripening of 'chorizo'-a Spanish dry sausage- elaborated by traditional and industrial processes have been studied. Total free fatty acids (FFA), carbonyls, volatile fatty acids (acetic acid), TBA number and individual FFA were determined. A marked increase of total free fatty acids was observed, although an increase of rancidity was not detected. Except in one of the batches studied in which a rise in carbonyls was reported, these compounds remained unchanged during the ripening in the rest of the batches analysed. No significant change occurred in the proportions of different free fatty acids during ripening in both types of 'chorizo'. There was a marked increase of acetic acid during the first days of ripening followed by a slow fall in the ultimate stages. PMID- 22061097 TI - Carcass physical and chemical composition of three fat-tailed breeds of sheep. AB - Physical and chemical compositions of carcasses of 73 intact ram lambs of three fat-tailed Iranian breeds; Karakul (K), Mehraban (M) and Baluchi (B) were studied. Lambs were 195 days old at slaughter. Weight of wholesale cuts and bone, fat trim and trimmed meat of each cut were recorded. Moisture, protein, ether extract and ash were determined in each of the deboned cuts. The higher (P < 0.01) proportion of leg and shoulder in K compared with those in the other two breeds was due to a smaller (P < 0.01) tail fat in the former breed. The breeds were not different for weight of wholesale cuts as percentage of tail-free carcases. Tail-free carcass of K lambs had the highest percentage of bone, protein and moisture, and those of M had the highest fat trim and the lowest bone as compared with the other breeds. The small-size Baluchi, which is well adapted to the sub-desert conditions, was the fattest of the breeds, as assessed by its highest ranking for percentage of ether extract in the carcass. On the basis of protein content, the values of M and B tail-free carcasses were 93% and 89% as high, respectively, as that for K. Differences among the breeds for the physical and chemical constituents of wholesale cuts as a percentage of the same component in half carcass without tail were small. On the basis of percentage protein, the values of shoulder, back and flap + neck were 102, 98 and 85% as high, respectively, as that for leg. PMID- 22061098 TI - Paris ham processing: Technological yield as affected by residual glycogen content of muscle. AB - The aim of the present experiment was to study the relationships between pH, protein and residual glycogen content of pig muscle on the one hand, and technological yield (TY) of Paris ham processing on the other (Paris ham is a type of cured cooked ham). Fifty-two pigs were slaughtered at 100 kg liveweight in a commercial abattoir, in four slaughter series. Ultimate pH, protein and glycogen were determined around 24h post mortem. Two days after slaughter, the right hams were processed to Paris ham. Residual glycogen levels varied from 0 to 78 MUmol/g of fresh tissue. All correlations between TY and the other traits under study were significant at the P < 0.05 level. Correlation between glycogen and TY was by far the highest one (r = 0t-0.60, P < 0.01). Protein content and both pH values gave similar but lower correlations with TY (r around 0.4, P < 0.01). It is concluded that the results of the present study agree with the hypothesis that the residual glycogen content of muscle has a direct effect on the technological yield of cooked ham processing. PMID- 22061099 TI - Effect of electrical stimulation, hip suspension and ageing on quality of chilled pig meat. AB - Carcasses from 60 Large white pigs, weighing 62-85 kg, were split and half were stimulated (700 V, 12.5 Hz for 90 s) 20 min after slaughter. Half of the stimulated (ES) and half of the non-stimulated sides were suspended from the Obturator foramen at 40 min after slaughter and resuspended from the Achilles tendon after 6 h. The sides were then subjected to one of two chilling treatments: (a) air at -15 degrees C until M. longissimus dorsi (LD) in the lumbar region was below 10 degrees C (approx. 3 h from slaughter), followed by air at 1 degrees C for the remainder of chilling; (b) air at 1 degrees C throughout. Rapid chilling increased toughness of LD but not M. semimembranosus (Sm). Stimulation improved tenderness in both muscles, increased drip loss in Sm and increased paleness in LD which could be reversed by rapid chilling. Pelvic suspension reduced drip and improved tenderness with similar magnitude to ES. Ageing improved tenderness in all except pelvic suspended sides but ES produced the most tender pork at 7 days. PMID- 22061100 TI - The measurement of light scattering and electrical conductivity for the prediction of PSE pig meat at various times post mortem. AB - Measurements of light scattering and electrical conductivity were made in the Longissimus dorsi (LD) and Semimembranosus (SM) muscles using the Fibre Optic Probe (FOP) and Quality Meter (QM), respectively, to assess their ability to estimate pig meat quality, particularly the occurrence of PSE meat. One-hundred and-fifty-three gilt carcasses were measured on three occasions post mortem (pm): 45 min (FOP(45) and QM(45)), 2h (FOP(2) and QM(2) and 24 h (FOP(u) and QM(u)). Measurements of pH were taken in the same anatomical position and at the same times. At 24 h pm muscle reflectance (GOFO value) and subjective colour assessments were made on the cut surface of the LD at the level of the last rib. Water-holding capacity (WHC) was estimated in a sample taken from the exposed surface of the LD by the solubility of sarcoplasmic and myofibrillar proteins. The FOP(45) predicted most accurately the WHC (R(2) = 0.49). Neither of the other quality measurements improved the prediction at 45 min pm. However, at 2h, adding QM(2) as a second independent variable improved prediction of WHC (R(2) = 0.58). At 24 h the combination of FOPu, QMu and GOFO did not improve the prediction of WHC (R(2) = 0.58). The best prediction used measurements of FOP(45), QM(2) and GOFO (R(2) = 0.62). The best relationship between subjective colour scores and the quantitative measurements of meat quality using discriminant analysis was obtained with the FOPu with an error-count estimate of 15.1% followed by FOP(2) (17%), GOFO value (18.7%), pH(2) (19.7%) and QMu (20.2%). With combination measurements of two instruments, pH(2) and FOP(2) had the lowest error-count estimate (10.9%). No further precision was obtained with combinations of three instruments. These results suggest that FOP and QM can be used to predict PSE and normal pig meat at different times pm and can replace traditional pH muscle measurements. PMID- 22061101 TI - Lipid and fatty acid composition of rabbit meat: Part 1.-Apolar fraction. AB - The apolar lipid contents and the fatty acid composition of meat from two rabbit breeds (New Zealand white and commercial hybrid HYLA) fed two commercial diets of different protein and crude fibre levels have been studied. The total and apolar lipid content of meat from both rabbit breeds ranged from 4.9 to 10.5% (wet weight). The individual lipid classes of the apolar fraction are described. Triglycerides accounted for more than 80% of total apolar lipids. The fat from rabbit meat is comparatively richer in palmitic acid (about 40% being always the major fatty acid), in linoleic acid and in myristic acid and poorer in stearic acid than other meats. Although differences in the fatty acid compositions of meat were observed, only clear influences of age, sex, breed, and/or feeding on the fatty acids C-16:0, C-18:0 and C-18:2 of total and apolar lipids were found. PMID- 22061102 TI - Lipid and fatty acid composition of rabbit meat: Part 2.-Phospholipids. AB - The phospholipid contents (and their fatty acid composition) of the meat of two rabbit breeds (New Zealand white and the commercial hybrid HYLA) fed with two commercial diets of different protein and fibre contents, have been determined. The phospholipid contents in the meat of both rabbit breeds ranged from 9% to 19% total lipid. In this fraction seven different phospholipid classes were detected but phosphatidylcholine (PC) and phosphatididylethanolamine (PE) had average percentages of 50 and 20 of the total phospholipids. The major fatty acids of both phosphatidylcholine and phosphatidylethanolamine were C-16:0, C-18:0, C-18:1 and C-18:2, these together representing more than 70% of the total fatty acids. In general, the PC had an higher saturated fatty acid content than PE, which had a lower percentage of C-16:0 but higher C-20:4. Although differences in the fatty acid composition of the phospholipid fractions of the rabbit meat were observed, the only clear influences of age, sex, breed, and/or feeding were found with the C-16:0, C-18:0 and C-18:2 fatty acids. PMID- 22061103 TI - Simple test for differentiation between fresh pork and frozen/thawed pork. AB - Enzyme profile of the exudates from fresh and frozen/thawed pork has been assayed by using a semi-quantitative method (APIZYM). Only three enzymes (esterase lipase, beta-glucuronidase and alpha-glucosidase) showed significant differences (P < 0.01) between fresh and frozen/thawed pork. Different storage conditions were tested (freezing temperature: -10 to -60 degrees C for 13 days and time of storage: 11 to 54 days at -18 degrees C) but no significant differences were found among them. The APIZYM system would constitute a simple method for detecting frozen/thawed pork. PMID- 22061104 TI - Two reading techniques of the filter paper press method for measuring meat water holding capacity. AB - Two systems of measuring the areas obtained from the filter paper press method (Grau & Hamm) on meat (beef) were compared: by planimeter (method A) and by optical-electronic system (Video Image Analyzer; method B). Data obtained by three operators, measuring 15 samples twice, were utilized to estimate the 'precision' of the two methods. The general mean area of ring zone resulting from method A was 6.69 cm(2). Analysis of variance demonstrated a significant influence both for 'operator' factor and for the interaction operator-sample. Repeatability and reproducibility were 0.1706 and 0.2580, respectively. By method B the general mean area was 6.67 cm(2). The variance among operators was significant, but lower than in the method A, and there was no interaction. The repeatability and reproducibility were 0.03055 and 0.07234, respectively. It would appear, therefore, that the optical-electronic determination is more precise than the planimetric method. PMID- 22061105 TI - Superiority of extra-pair offspring: maternal but not genetic effects as revealed by a mixed cross-fostering design. AB - Extra-pair copulations (EPC) are the rule rather than an exception in socially monogamous birds, but despite widespread occurrences, the benefits of female infidelity remain elusive. Most attention has been paid to the possibility that females gain genetic benefits from EPC, and fitness comparisons between maternal half-siblings are considered to be a defining test of this hypothesis. Recently, it was shown that these comparisons may be confounded by within-brood maternal effects where one such effect may be the distribution of half-siblings in the laying order. However, this possibility is difficult to study as it would be necessary to detect the egg from which each chick hatched. In this study, we used a new approach for egg-chick assignment and cross-fostered eggs on an individual basis among a set of nests of the collared flycatcher Ficedula albicollis. After hatching, chicks were ascribed to mothers and therefore to individual eggs by molecular genetic methods. Extra-pair young predominated early in the laying order. Under natural conditions, this should give them a competitive advantage over their half-siblings, mediated by hatching asynchrony. However, we experimentally synchronized hatching, and after this treatment, extra-pair young did not outperform within-pair young in any studied trait including survival up to recruitment and several indicators of reproductive success and attractiveness. We obtained only modest sample sizes for the last two traits and did not test for extra-pair success of male offspring. Thus, we cannot exclude the possibility of advantages of extra-pair young during the adult phase of life. However, our data tentatively suggest that the more likely reason for females' EPCs is the insurance against the infertility of a social mate. PMID- 22061106 TI - Artificial extracellular matrices composed of collagen I and sulfated hyaluronan with adsorbed transforming growth factor beta1 promote collagen synthesis of human mesenchymal stromal cells. AB - Sulfated glycosaminoglycans (GAG) are multifunctional components of the extracellular matrix and are involved in the regulation of adhesion, proliferation and differentiation of cells. The effects of GAG are mediated in general by their interactions with cations and water, and in particular by their binding to growth factors. The aim of this study was to generate artificial extracellular matrices (aECM) containing collagen I and hyaluronan sulfate (HyaS), which are capable of adsorbing and releasing transforming growth factor beta1 (TGF-beta1), and to promote collagen synthesis of cultured human mesenchymal stromal cells (hMSC). For the preparation of aECM, monosulfated Hya (HyaS1) or trisulfated Hya (HyaS3) were used; the natural chondroitin-4-sulfate was used as a control. As applied for the in vitro experiments, the resulting matrices were composed of 93-98% collagen I and 2-7% GAG derivative. Adsorption of TGF-beta1 to the aECM and release from the aECM was dependent on the degree of sulfation of hyaluronan. Collagen synthesis of hMSC was promoted only by aECM with adsorbed TGF-beta1; the bare aECM had a slightly inhibitory effect on collagen synthesis. The promoting effect did not correlate either to the amount of adsorbed TGF-beta1 nor to the release of TGF-beta1, indicating that the correct presentation of TGF-beta1 to the cells might be critical. The results indicate that sulfated hyaluronan-containing aECM have the potential to control both the adsorption and release of TGF-beta1, and thereby promote collagen synthesis of hMSC. Thus, these aECM might be a useful tool for different tissue engineering applications to enhance bone formation when used for biomaterial coating. PMID- 22061107 TI - Sustained release of adiponectin improves osteogenesis around hydroxyapatite implants by suppressing osteoclast activity in ovariectomized rabbits. AB - Lack of estrogen could lead to decreased bone mass and increased risk for osteoporosis, which has a negative influence on biomaterial implantation. Adiponectin (APN), an adipose-derived hormone, has been shown to increase bone density by inhibiting osteoclast formation and promoting the formation of osteoblasts. This study was designed to investigate the direct effects of APN released from the Matrigel controlled-release system on the activity of rabbit mature osteoclasts and osteoclast precursor RAW264.7 cells in vitro, and to determine its effects by improving osteogenesis around the hydroxyapatite (HA) implant in ovariectomized (OVX) rabbits. APN+Matrigel+HA, APN+HA, Matrigel+HA and HA were implanted into mandibular defects of OVX rabbits. At 4 weeks after implantation, the mandibles were examined by histology, microcomputed tomography and biomechanical testing. The results demonstrated that Matrigel extended the length of APN released to achieve long-term persistence. The sustained release of APN suppressed the osteoclastic activity both in vitro and in vivo, and improved the peri-implant osteogenesis in OVX rabbits, while the short-term APN treatment did not. Sustained release of APN may be an effective strategy to improve the restoration of bone defects by the use of HA materials under osteoporotic conditions in which osteoclasts are highly activated. PMID- 22061108 TI - Maleimide-thiol coupling of a bioactive peptide to an elastin-like protein polymer. AB - Recombinant elastin-like protein (ELP) polymers display several favorable characteristics for tissue repair and replacement as well as drug delivery applications. However, these materials are derived from peptide sequences that do not lend themselves to cell adhesion, migration, or proliferation. This report describes the chemoselective ligation of peptide linkers bearing the bioactive RGD sequence to the surface of ELP hydrogels. Initially, cystamine is conjugated to ELP, followed by the temperature-driven formation of elastomeric ELP hydrogels. Cystamine reduction produces reactive thiols that are coupled to the RGD peptide linker via a terminal maleimide group. Investigations into the behavior of endothelial cells and mesenchymal stem cells on the RGD-modified ELP hydrogel surface reveal significantly enhanced attachment, spreading, migration and proliferation. Attached endothelial cells display a quiescent phenotype. PMID- 22061109 TI - Short-term feeding strategies and pork quality. AB - Two experiments were done to determine whether short-term supplementation (5 days pre-slaughter) with magnesium acetate, or a combination of magnesium acetate, tryptophan, vitamin E and vitamin C would improve pork quality. In the first experiment the pigs (Pietrain*Yorkshire, n=96) were fed a standard feed or a magnesium supplemented feed for 5 days prior to slaughter. As a possible stress factor half of the animals were slaughtered upon arrival at the slaughterplant whereas the remaining animals were allowed two hours of rest in lairage before slaughter. Magnesium supplementation did not result in an increase in plasma magnesium concentration at slaughter. Omission of lairage resulted in higher plasma glucose concentrations, but plasma lactate concentrations were not affected. Drip loss and ultimate pH were not affected by diet or omission of lairage. Omission of lairage resulted in poorer color characteristics. This effect was prevented by supplementation with magnesium. In the second experiment the pigs (Pietrain*Yorkshire, n=92) were fed a standard feed or this standard feed supplemented with magnesium acetate, tryptophan, vitamin E and vitamin C for 5 days prior to slaughter. Supplementation with vitamin E did not increase muscle vitamin E concentration. Inclusion of supplements in the diet failed to improve water-holding capacity or color characteristics. These results indicate that short-term supplementation with magnesium acetate, tryptophan, vitamin E and vitamin C is of little value in improving pork quality when pigs are not stressed beyond levels associated with routine slaughter procedures. PMID- 22061110 TI - Lemon albedo as a new source of dietary fiber: Application to bologna sausages. AB - The aim of this work was to study the effect of the addition of lemon albedo in bologna sausages. Two types of albedo (raw and cooked) and five concentrations (0%, 2.5%, 5%, 7.5% and 10%) were added to sausages. Chemical, physicochemical and sensory analyses were made. The addition of albedo to bologna sausages represents an improvement in their nutritional properties and may have beneficial effects, possibly due to the presence of active biocompounds which induce a decrease in residual nitrite levels. The formulations which gave products with sensory properties similar to conventional sausages were sausages with 2.5% and 5% raw albedo and 2.5%, 5% and 7.5% cooked albedo. PMID- 22061111 TI - Lack of effects of hyperkalemia on the metabolism of normoxic or anoxic rabbit triceps brachii muscle. AB - Rabbit triceps brachii muscle was perfused with bovine red cells medium. Changes in phosphorus compounds and intracellular pH were followed using (31)P NMR during 15 min in the perfused muscle and during 50 min in muscle made anoxic by perfusion stop. Potassium levels in perfusate was maintained at 4 mM (normal plasma concentration at rest) during all perfusion in one muscle and at 4 mM for 10 min then 10 mM during 5 min before perfusion stop in the contralateral muscle. The intracellular pH and phosphorylated compounds content remained stable in the perfused muscle whatever the potassium concentration of the perfusate. Five min after perfusion stop a decrease in phosphocreatine (P<0.05) and pH (P<0.01) and an increase in sugar-phosphates (P<0.01) were observed independently of potassium concentration. The lack of effect of increasing circulating potassium indicates that hyperkalemia does not affect, by itself the muscles energetic metabolism. PMID- 22061112 TI - N-terminal amino acid sequences of troponin T fragments, including 30 kDa one, produced during postmortem aging of bovine longissimus muscle. AB - We have determined the amino (N)-terminal amino acid (AA) sequences of five troponin T (TnT) fragments produced during postmortem aging of bovine longissimus muscle. Western blot analysis showed that 32.1, 28.8, 27, and 25.8 kDa anti-fast type TnT (fTnT)-positive fragments and a 31 kDa anti-slow-type TnT (sTnT) positive fragment were present at 14 d postmortem. The N-terminal AA sequences of the 32.1, 28.8 (conventional 30 kDa), 27, and 25.8 kDa fragments were APPPPAEV, EVHEPEEK, EKPRPRLT, and APKIPEGE, respectively, and they were mapped to the N terminal region of bovine fTnT isoforms. The N-terminal sequences of the 31 kDa fragment, EAPEEPEP, were mapped to the sTnT isoforms. These findings indicate that the two isoform types of fTnT predominantly expressed in the longissimus muscle are cleaved specifically at Glu(21)-Ala(22) and Glu(15)-Ala(16), His(37) Glu(38) and His(31)-Glu(32), Glu(43)-Glu(44) and Glu(37)-Glu(38), and/or Thr(51) Ala(52) and Thr(45)-Ala(46), respectively, and that a sTnT isoform is cleaved specifically at Glu(23)-Glu(24). PMID- 22061113 TI - The use of the MRI technique in the evaluation of water distribution in tumbled porcine muscle. AB - The non-destructive magnetic resonance imaging (MRI) technique was used to study the spatial distribution of water in meat samples without and with brine and the influence of injection curing on water distribution in cured meat. Fresh non treated porcine ham muscles (m. biceps femoris) were used; muscles injected with curing salt and subjected to half-time tumbling (3 h and 20 min) and full-time tumbling (6 h and 40 min) were studied. A "Lutetia" type 4 tumbler of French manufacture with a helicoidal paddle and a 2000 kg drum capacity was used. Histological examination of fresh non-treated muscles, after brine injection, and during and after the completion of tumbling demonstrated considerable differences. The use of MRI made it possible to estimate the effect of the tumbling procedure on the dynamics of brine migration and binding by muscle proteins. The spatial imaging of the proton density distribution confirmed that with longer meat tumbling times the binding of brine and its uniform distribution in the muscles increased. PMID- 22061114 TI - Decreasing variation in the eating quality of beef through homogenous pre- and post-slaughter management. AB - The objective of this experiment was to determine the effectiveness of current "best-practise" management of steers pre- and post-slaughter in reducing variation in the eating quality of beef. Steers sired by one Belgian Blue bull from Holstein-Friesian cows were managed optimally from birth to slaughter. Animals were slaughtered at target body weights and subcutaneous fat scores of 620 kg and 4L (LH) (n=23) or 720 kg and 4H (HH) (n=24). On each slaughter occasion, commercial steers with similar carcass weights and classification scores to the homogenous steers were selected from the factory lairage; n=19 for light commercial steers (LC) and n=20 for heavy commercial steers (HC). Carcasses were hung by the pubic bone at 10 degrees C for 10 h and 2 degrees C until 24 h postmortem, when M. longissimus dorsi and M. semimembranosus muscles were excised. Following ageing for 2, 7 and/or 14 days postmortem, eating quality was assessed. Muscle from HH steers was more variable in terms of tenderness, protein, moisture and water-holding capacity compared to muscle from LH steers within LD muscle. Muscle from HC steers was more variable in terms of tenderness, redness colour, protein and intramuscular fat compared to muscle from LC steers within LD muscle. Applying best practice management to the homogenous and commercial steers in the present experiment reduced variances in Warner Bratzler shear force (25.69 and 23.9, respectively) compared to variance (154.9) of previous research carried out by the present authors. PMID- 22061115 TI - Fatty acid composition and cholesterol content of muscles as related to genotype and vitamin E treatment in crossbred lambs. AB - Various factors (weight, sex, diet and breed) influence meat lamb fatty acid composition. The present study was undertaken to evaluate the lipid profile in two different lamb types. Sixty crossbred lambs (Ile de France*Pagliarola and Gentile di Puglia*Sopravissana) were used to determine cholesterol, lipid content and fatty acid profile of Longissimus dorsi, Semimembranosus and Gluteobiceps muscles. Moreover, the effect of vitamin E treatment in vivo on propensity of the lamb meat to lipoperoxidation was assessed. In both crossbreeds total muscle lipids ranged between 2.4 and 4.0 mg/100 g. In the Ile de France*Pagliarola lambs a lower percentage of saturated fatty acids and a low atherogenic index were found. The vitamin E treatment reduced significantly the lipoperoxidation, without difference between the two crossbreeds. PMID- 22061116 TI - Comparison of modified atmosphere packaging and vacuum packaging for long period storage of dry-cured ham: effects on colour, texture and microbiological quality. AB - Slices of dry-cured hams (Biceps femoris muscle) were stored during 8 weeks under vacuum and modified atmospheres (100% N(2) and a mixture of 20% CO(2) and 80% N(2)) in order to study the modifications on colour, texture and microbial counts during that period. Lightness was found to be more stable when samples were stored with 20% CO(2) and 80% N(2) without statistical differences between vacuum and 100% N(2). A slight whiteness was observed in the vacuum packed samples. Yellowness increased during time in vacuum packed samples, although no differences were found among the three conditions at the end of the study. Redness values were not affected by time or by the packaging system. With regard to texture, values found for all samples were within the normal range for this type of products, although it was observed that modified atmosphere packaging preserved samples better from hardening than vacuum packaging. No safety problems were detected in relation to the microbial quality in any case. In general, no clear differences were found among the three packaging systems for colour, texture and microbial quality in the storage conditions studied. PMID- 22061117 TI - Effects of interesterified vegetable oils and sugarbeet fiber on the quality of frankfurters. AB - The effects of interesterified vegetable oils (IVOs) prepared from palm, cottonseed and olive oil, respectively, and sugarbeet fiber (SBF) on quality of frankfurters have been studied. Beef fat (10%) was replaced by one of the IVOs for 60% and 100%. Incorporation of IVOs in frankfurters improved the nutritional content of product due to altering the fatty acid composition. The oleic acid content of frankfurters increased from 28.76% to 45.57% and 47.15% as the interesterified palm oil (IPO) and interesterified olive oil (IOO) contents increased from 0% to 10% and 6%, respectively. The linoleic acid contents of 6% and 10% interesterified cottonseed oil (ICO) added frankfurters were, respectively, 10- and 19.6-fold higher than treatments without ICO. Addition of SBF (<425 MUm size and 1% level) significantly increased (p<0.05) the total dietary fiber content and water-holding capacity (WHC) of frankfurters. Incorporation of IVOs and SBF did not lead to significant changes in appearance, colour, texture, flavour or sensory scores. It is concluded that IVOs and SBF may be successfully applied as beef fat substitute in frankfurters since this combination offset some of the changes brought about by beef fat replacement. PMID- 22061118 TI - Colour, composition and eating quality of beef from the progeny of two Charolais sires. AB - Eating quality and variation within eating quality attributes of beef from young bull progeny of a Charolais sire of average conformation heritability (CF44) (n=14) and young bull progeny of a Charolais sire of good conformation heritability (IC27) (n=16) were examined. The M. longissimus dorsi (up to 12th and/or 13th ribs) was excised 24 h post-slaughter and eating quality attributes analysed at 2, 7 and 14 days postmortem. While progeny muscularity and carcass weight reflected that of each sire, in general no variation was observed in the quality attributes. In addition no significant difference in mean values was evident between sire progenies for carcass and meat quality attributes examined. Significant variation was observed in colour after 2 days ageing, but this was not evident after 7 or 14 days ageing. Average sarcomere length did differ significantly (p<0.05) between progeny of both sire types (CF44=1.87 MUm and IC27=1.77 MUm), but did not appear to impact on tenderness. The similarity between the progeny of the average or good conformation sires examined in this experiment suggests such sires have no effect on the eating quality of their young bull beef progeny. PMID- 22061119 TI - Effects of dietary vitamin D(3), vitamin E, and magnesium supplementation on pork quality. AB - Meat quality traits and palatability characteristics were evaluated on 240 barrows and gilts subjected to one of eight dietary regimens: (1) control (no supplement), (2) vitamin D(3)(D(3)), (3) vitamin E (E), (4) magnesium (Mg), (5) vitamins D(3) and E (D(3)/E), (6) vitamin D(3) and magnesium (D(3)/Mg), (7) vitamin E and magnesium (E/Mg), and (8) vitamins D(3) and E, and magnesium (D(3)/E/Mg). Barrows supplemented with D(3)/E/Mg had the highest (P>0.05) ultimate pH. Those supplemented with E had a higher ultimate pH than those supplemented with D(3)/Mg or the control. Gilts supplemented with Mg had the highest ultimate pH of all of the gilts while those supplemented with D(3) had the lowest. Barrows supplemented with Mg or E had more marbling than those supplemented with D(3) or D/E. Gilts supplemented with Mg had the most marbling when compared to other gilts. At 48 h postmortem, no differences due to dietary treatment were observed in L (*), a (*) or b (*) value, drip loss or purge loss. At 14 days postmortem, no differences due to diet existed in sensory characteristics. Results suggest that supplementation of swine diets with some dietary supplement combinations of containing Mg may have some potential benefit for increasing ultimate pH. PMID- 22061120 TI - Myosin heavy chain isoforms expressed in bovine skeletal muscles. AB - Nucleotide sequences including the full coding region for three types of myosin heavy chain (MyHC) isoforms were determined from bovine adult skeletal muscles. The deduced amino acid sequences were 1940, 1938, and 1935 residues for the MyHC 2a, -2x, and -slow, respectively. Like other mammalian MyHC isoforms, the bovine MyHC isoforms had homologous sequences except for substitutions concentrated on the loop 1, loop 2, and light chain binding regions. RT-PCR amplifications showed that the adult bovine skeletal muscles expressed the MyHC-2a, -2x, and -slow isoforms but no -2b isoform. The absence of the MyHC-2b isoform and substitutions on the loop2 region could explain some differences in meat quality between beef and pork. PMID- 22061121 TI - A Zn-porphyrin complex contributes to bright red color in Parma ham. AB - The Italian traditional dry-cured ham (Parma ham) shows a stable bright red color that is achieved without the use of nitrite and/or nitrate. In this study we examined the pigment spectroscopically, fluoroscopically and by using HPLC and ESI-HR-MASS analysis. Porphyrin derivative other than acid hematin were contained in the HCl-containing acetone extract from Parma ham. A strong fluorescence peak at 588 nm and a weak fluorescence peak at 641 nm were observed. By HPLC analysis the acetone extract of Parma ham was observed at the single peak, which eluted at the same time as Zn-protoporphyrin IX and emitted fluorescence. The results of ESI-HR-MS analysis showed both agreement with the molecular weight of Zn protoporphyrin IX and the characteristic isotope pattern caused by Zn isotopes. These results suggest that the bright red color in Parma ham is caused by Zn protoporphyrin IX. PMID- 22061122 TI - Predicting temperature profiles to determine degree of doneness for beef biceps femoris and longissimus lumborum steaks. AB - The degree of steak doneness is an important factor in providing consumers with a satisfying eating experience. Endpoint temperature and cooking rate are the determinants of degree of doneness. Our objectives were to predict internal temperature profiles and cooking times for longissimus lumborum and biceps femoris steaks. Each biceps femoris and longissimus lumborum steak was cooked individually in a gas-fired, forced-air-convection oven at 163 degrees C until the center temperature of each steak reached 70 degrees C. Temperature profiles were recorded by a Doric temperature recorder and the recorded time and temperature data were imported into a spreadsheet. A prediction method was then implemented to predict cooking times and temperature profiles. No significant differences (p<0.05) were found in cooking times between experimental and predicted values for either longissimus lumborum or biceps femoris steaks. Good agreement was found between experimental and predicted temperature profiles for the longissimus lumborum muscle. However, predicted temperature profiles were consistently higher (except for the beginning of the cooking cycle) than the experimental values up to 65 degrees C in the cooking cycle for biceps femoris steaks. A highly positive linear relationship was found between experimental and modeled temperature profiles for longissimus lumborum (R(2)=0.99), whereas a high quadratic (R(2)=0.99) relationship was found for biceps femoris steaks. Our method for predicting temperature profiles of steaks for a specified cooking time to attain a given degree of doneness should increase consumer satisfaction by reducing variation in meat sensory traits related to an expected degree of doneness. PMID- 22061123 TI - Industrial application to cattle of a method for the early determination of meat ultimate pH. AB - A method to measure the approximate glycolytic potential of slaughter animals, and thus the ultimate pH, was applied for several months on the slaughter line of a cattle abattoir. The patented method (WO 00112844) determines a so-called glucose value from the hydrolysis of glycogen in a sample of Longissimus lumborum. The value is available before the dressed carcass is weighed and graded. The 13,700 cattle tested were pasture-fed bulls and 'prime' animals, the latter comprising steers and virgin females. The method was used to sort carcasses into two quality grades, table cuts and manufacturing, according to a threshold glucose value that in this application corresponded to an ultimate pH of 5.70. In frequency distributions the glucose value was roughly normally distributed for prime animals but for bulls was lower on average and strongly skewed to low values. The distributions showed that 19% of prime and 62% of bulls had an ultimate pH below 5.70. The results were consistent with prior survey work undertaken in New Zealand with conventional pH measurements made a day after slaughter. Error in the method is examined with respect to commercial outcomes. For most errors the method 'fails-safe', in that normal pH animals are more likely to be classed as high pH than vice versa. In a second phase of the study, meteorological and some abattoir data are related to mean daily glucose values and their variance. The more bulls slaughtered per day the lower the mean glucose value for bulls (r=-0.25, P<0.01), an effect presumably arising from mixing unfamiliar groups of bulls. There was a decrease in mean glucose value with higher maximum daily temperature (P<0.01). Periods of rainfall in the days leading to slaughter were positive for glucose value. For both bulls (especially) and prime, the lower the mean glucose value, the greater the percent variance (r= 0.81 and -0.56, P<0.001) but the cause of this could not be established. PMID- 22061124 TI - The roles of the proteasome, and cathepsins B, L, H and D, in ostrich meat tenderisation. AB - As very little research has been conducted on ostrich meat tenderisation, this study aims at investigating the roles of the proteasome and cathepsins B, L, H, and D in the tenderisation process. The enzyme activities in meat from eight ostriches during a 12-day ageing period and the corresponding physical characteristics (e.g. pH, shear force) and myofibril patterns were determined. After 12 days, substantial high remaining activities were found, especially of the proteasome, thus implicating their possible roles in the tenderisation process. The mean shear force values, however, showed no improvement in tenderness, but the myofibril patterns showed the appearance of a M(r) 32 K component. Myofibril degradation studies of the proteasome, analysed electrophoretically, also revealed a possible role of the proteasome, but under activating conditions. This study provides further insights into the tenderisation process, particularly of ostrich meat, which may ultimately be used for the advantageous manipulation of the process. PMID- 22061125 TI - The effect of repeat application of electrical stunning on the welfare of pigs. AB - Although legislation requires the production of immediate insensibility, implying that a stun can be applied only once, the practice of repeat application of electrical stunning is common. However, the relative consequences of such repeat applications are unknown. This study investigated the effects of repeat applications of electrical stunning (200 V, 50 Hz) following different delays of 15, 60 or 180 s between the initial stun and the repeat applications. The parameters examined, following stunning, were the durations of spontaneous physical activity, time to return of reflexes and the duration of the epileptiform activity in the electrocorticogram. The results showed that repeat application of electrical stunning can produce successive epileptic activity and therefore an effective stun. The duration of tonic and clonic phase activity following repeat application was significantly shorter than after a single stun only. There was a tendency for the reflexes to return more quickly following repeat application. The use of electrical stunning to re-stun pigs appears to raise no welfare concerns and although commonly used, should only be applied out of necessity rather than as routine practice. PMID- 22061126 TI - Effects of enhancing beef longissimus with phosphate plus salt, or calcium lactate plus non-phosphate water binders plus rosemary extract. AB - Beef strip loins (n=36) were enhanced with a sodium phosphate plus salt solution (PS); or with a calcium lactate solution (Ca) plus 1% or 2% beef broth (Br) plus natural flavoring (N) containing rosemary extract; or with 1% or 2% kappa carrageenan (Cr) plus N to determine effects of ingredients on color life, water binding ability, and palatability traits. Enhancement with PS resulted in higher pH, higher pumped yields, greater water-binding ability, and higher tenderness and juiciness scores than enhancement with Ca (all p<0.05). Enhancement with Ca resulted in less color deterioration, less metmyoglobin discoloration, higher L (*), a (*), and b (*) values, higher beef flavor intensity scores and lower off flavor scores than enhancement with PS (all p<0.05). Warner-Bratzler shear values did not differ among treatments. Steaks enhanced with Br had less color deterioration, less metmyoglobin discoloration, and higher L (*) values than those enhanced with Cr (all p<0.05). Pumped yields were not different between loins enhanced with Br or Cr. The N flavoring containing rosemary extract decreased (p<0.05) discoloration. Enhancing beef longissimus with PS increased water-binding capacity and sensory tenderness traits, but reduced color stability and increased off-flavors, whereas Ca preserved color stability and enhanced flavor at the expense of pumped yields. The use of Br or Cr had no influence on tenderness or palatability traits. PMID- 22061127 TI - Myosin heavy chain isoforms influence myofibrillar ATPase activity under simulated postmortem pH, calcium, and temperature conditions. AB - The pH and Ca(2+) sensitivity of myofibrillar ATPase activity plays an integral role in regulating postmortem muscle ATP utilization and likely paces postmortem glycolysis. The objective of this study was to determine the influence of pH and Ca(2+) concentration on the ATPase activity of myofibrils from red semitendinosus (RST) and white semitendinosus (WST) porcine muscles. Myofibrillar ATPase was measured at 39 degrees C over a pH range 5-7.5 and a [Ca(2+)] range pCa 4-9 (10( 4)-10(-9)M). At maximum Ca(2+)-dependent activation (pCa 4), RST myofibrils had lower (p<0.0001) ATPase activity than WST myofibrils. This maximum activity of myofibrils from both muscle regions was not influenced from pH 7.5 to 6.5, declined between pH 6.5 and 5.75 (Hill coefficient, n(H)=2.7-3.4; pH at half maximum activity, pH(50)=5.97) and was near zero at pH 5.5. At pH 7, pCa-activity relationships showed that RST required less Ca(2+) for half-maximum activation (higher pCa(50); 6.50) than WST myofibrils (pCa(50)=6.35) but had no difference in n(H). At pH 7, both RST and WST myofibrils had maximum Ca(2+)-dependent, actin activated ATPase activity at pCa ?6 and Ca(2+)-independent myosin ATPase activity at pCa ?6.75. pCa-activity relationships at different pH levels indicated that pCa(50) decreased with pH from pH 6.5 to 6.125 in both RST and WST myofibrils. At pH <5.75, [Ca(2+)] did not influence ATPase activity in RST or WST myofibrils. These data show that myofibrils with predominantly fast MyHC (WST) have a higher actin-activated myosin ATPase activity than myofibrils with primarily slow MyHC isoforms (RST) at Ca(2+) concentrations and pH values characteristic of postmortem muscle. PMID- 22061128 TI - Isolation and technological properties of coagulase negative staphylococci from fermented sausages of Southern Italy. AB - The aims of this study were to characterize the population of Micrococcaceae in different types of fermented sausages of Southern Italy and to determine the technological properties of Staphylococcus strains in order to evaluate the suitability of selected strains as starter cultures in the processing of dry fermented pork sausages. Ninety-six strains were studied to evaluate nitrate reductase, proteolytic, lipolytic and antioxidant activities as well as growth ability at different temperatures, pH's and NaCl concentrations. All the strains were classified as Staphylococcus except for one isolate assigned to Kocuria spp. The species most often isolated were S. saprophyticus, S. xylosus and S. equorum, although they were not equally distributed within the different sausages. Other species isolated were, in descending order of abundance, S. succinus, S. warneri, S. lentus, S. vitulus, S. pasteuri, S. epidermidis, and S. haemolyticus. In general, the S. xylosus strains exhibited the best technological properties that would make them eligible as good starter cultures for fermented meat products. However, strains belonging to other species also showed good technological properties. Finally, all strains grew at 10, 15 and 20 degrees C, in the presence of 10% and 15% of NaCl and at pH 5.0 and 5.5. The results showed that it is possible to formulate a broad variety of staphylococcal starter cultures, adaptable to different technological conditions and sausage manufacture practices. PMID- 22061129 TI - Profile and effects of consumer involvement in fresh meat. AB - This study investigates the profile and effects of consumer involvement in fresh meat as a product category based on cross-sectional data collected in Belgium. Analyses confirm that involvement in meat is a multidimensional construct including four facets: pleasure value, symbolic value, risk importance and risk probability. Four involvement-based meat consumer segments are identified: straightforward, cautious, indifferent, and concerned. Socio-demographic differences between the segments relate to gender, age and presence of children. The segments differ in terms of extensiveness of the decision-making process, impact and trust in information sources, levels of concern, price consciousness, claimed meat consumption, consumption intention, and preferred place of purchase. The two segments with a strong perception of meat risks constitute two-thirds of the market. They can be typified as cautious meat lovers versus concerned meat consumers. Efforts aiming at consumer reassurance through quality improvement, traceability, labelling or communication may gain effectiveness when targeted specifically to these two segments. Whereas straightforward meat lovers focus mainly on taste as the decisive criterion, indifferent consumers are strongly price oriented. PMID- 22061130 TI - Water transfer analysis in pork meat supported by NMR imaging. AB - NMR proton density imaging was used to study isothermal and unidirectional drying of pork semi membranosus muscle samples at temperatures of 12, 16 and 20 degrees C. An independent calibration of the transversal relaxation time T(2) as a function of the moisture content was carried out to convert the signal amplitude into moisture content. Due to spatial heterogeneity in drying, 2D images were needed to assess the evolution of 1D moisture profiles. The relationship between the effective water diffusivity (D) was calculated in function of water content (X) using the Boltzman transformation which needs no a priori on the relationship D=f(X); the effect of lipid content, temperature and fibre direction on this relationship were also studied. In all cases a decrease in water content brought about a decrease in D. A slight increase in lipid content led to a dramatic decrease in D. The fibre direction relative to water movement had a negligible effect. No significative differences in D between the three temperatures were observed, due to variability in the chemical composition of the samples. PMID- 22061131 TI - A research note on radio frequency transponder effects on bloom of beef muscle. AB - This study was designed to determine if radio frequency transponders affect the bloom of tray-packed beef muscle. A radio frequency identification (RFID) passive transponder was applied to the overwrap film of beef strip loin steaks. Overwrapped tray packs were vacuum packaged and stored for two days at 4 degrees C. Samples were removed from the vacuum package and CIE L(*), a(*), and b(*) values were measured through the overwrap until CIE a(*) values stabilized (40 min). Overwrap was removed and CIE L(*), a(*), and b(*) values were measured directly below the RFID and an adjacent control area for 40 min. All CIE L(*), a(*), and b(*) values were statistically different (P<0.05) directly below the RFID when compared to the adjacent control area. The greatest differences were observed in the initial values and may be of consumer concern. After achieving full bloom (40 min post-overwrap removal), the difference between these areas were negligible. PMID- 22061132 TI - Effects of outdoor rearing and sire breed (Duroc or Yorkshire) on carcass composition and sensory and technological meat quality. AB - The effects of outdoor rearing and sire breed on carcass composition and technological and sensory meat quality in pigs were studied in a trial with 102 crossbred slaughter pigs (Yorkshire, or Yorkshire * Landrace sows and Duroc or Yorkshire as terminal sire). Half of each litter were reared conventionally indoors, while the remainder were reared outdoors in a 50 000 m(2) area, as a single group. All pigs were fed ad libitum. Yorkshire sired pigs had significantly leaner carcasses and meat with lower IMF content and marbling scores, and higher shear force and water content. The sire breeds did not differ regarding pH(u), water-holding capacity, or colour. Meat from the Yorkshire crosses was more acid, less tender and gained lower overall acceptance scores in the sensory test. The outdoor-reared pigs had lower daily gain values and leaner carcasses. They produced meat with lower pH(u), higher drip loss, higher shear force values and higher internal reflectances. Their meat contained more lactate and crude protein and had a higher glycolytic potential, less IMF and less water. Regarding the sensory qualities, outdoor rearing impaired tenderness, juiciness and overall acceptance. PMID- 22061133 TI - Rapid DNA purification for Hal gene PCR diagnosis in porcine tissues and extension to other meat species. AB - Two different halothane (Hal) gene polymerase chain reaction (PCR) tests were applied to genomic DNA extracted from porcine blood, semen, muscle and fat tissues by a rapid and simple Chelex-100 based method. One of the PCR procedure is designed from the ryanodine receptor coding sequence to produce a 81 base pair (bp) fragment, while the other is designed from pig intron sequences to produce a 659 bp fragment. Oligonucleotide primers derived from the coding sequence were also used for other meat species. Amplification products obtained from porcine, bovine, ovine, equine and deer genomic DNA were successfully digested with Hha I restriction enzyme to produce the same electrophoretic pattern as in the normal homozygous (NN) pig. No PCR products could be amplified from chicken and turkey DNA. PMID- 22061134 TI - Gelatine colour measurement. AB - Gelatine colour is of commercial and scientific significance and yet there is no nationally accepted method for its measurement. On analysis it was found that light scatter due to imperfect filtration and molecular size (Veis, 1964) were the sources of interference. Colour measurements using a particular set-up of the BYK-Gardner Color-View Spectrophotometer were found to measure the colour of molten gelatine solutions from the Bloom strength determination, by reflectance, in agreement with visual colour values (r = 0.97), ascribed in accord with Beer's law. Type A and Type B gelatines (67), with turbidities of <80 NTU, from a wide range of raw materials and manufacturers were assessed. PMID- 22061135 TI - The effect of dietary vitamin E supplementation on the quality of fresh and frozen lamb meat. AB - The effect of dietary alpha-tocopheryl acetate supplementation on the uptake of alpha-tocopherol in ewe plasma, lamb plasma, milk, organs and muscles was investigated. The oxidative stability and colour in fresh M. longissimus dorsi and frozen M. longissimus dorsi, M. psoas major and M. gluteus medius were also investigated. Ewes (n = 12) were selected and scanned to assess pregnancy. They were divided into two groups (n = 6). The control group was fed a diet containing 20 mg alpha-tocopheryl acetate/kg feed/day and the supplemented group fed a diet containing 1000 mg alpha-tocopheryl acetate/kg feed/day, for 9 weeks ante parturition and 3 weeks post-parturition. The lambs were weaned at 3 weeks and fed supplemented or basal feed for 10 weeks before slaughter. Plasma alpha tocopherol increased significantly (p < 0.01) in ewes in the 9 weeks ante parturition, and lamb plasma taken just before slaughter was significantly (p < 0.01) higher for the supplemented group than the basal group, following 13 weeks of supplementation. Milk alpha-tocopherol levels were significantly (p < 0.01) higher from ewes fed the supplemented diet at parturition and for the three weeks of supplementation post-parturition (p < 0.05). Supplementation increased the alpha-tocopherol levels in all tissues sampled. The alpha-tocopherol concentrations in M. longissimus dorsi and M. psoas major were also determined after frozen storage at -20 degrees C for 34 weeks. Frozen storage resulted in a significant (p < 0.01) reduction in mean alpha-tocopherol levels for M. longissimus dorsi but not M. psoas major. Dietary supplementation with alpha tocopheryl acetate significantly (p < 0.05) increased the oxidative stability of lamb muscle. Surface colour (Hunter L, a, b) was found to be negatively correlated with metmyoglobin content. Supplementation reduced surface discolouration in refrigerated display under fluorescent light over a 6-7 day storage period. The effect was more pronounced in frozen displayed muscles than in freshly displayed samples. PMID- 22061136 TI - Microwave oven application in the extraction of fat from the subcutaneous tissue of Iberian pig ham. AB - The fat from subcutaneous tissue samples of Iberian pigs was extracted by solvent (2:1 chloroform-methanol) and by the action of microwave energy. The samples of liquid fat obtained by both extraction techniques were analysed by gas chromatography. Paired comparisons showed no significant differences in fatty acids in suggesting that the fat obtained by the two techniques was the same and that the extraction of fatty acids by microwaves is suitable for quality classification of Iberian pig carcasses. PMID- 22061137 TI - Sodium hydroxide and sodium tripolyphosphate effects on bind strength and sensory characteristics of restructured beef rolls. AB - Restructured beef rolls formulated with 1% NaCl (controls) or with 1% NaCl plus 0.07% NaOH or 0.375% sodium tripolyphosphate (STPP) had different (p < 0.05) relative bind strength and cooked yield, as follows: STPP > NaOH > controls. Percent cooked yield was inversely affected (p < 0.05) by added water level (5 > 10 > 20%). Bind values were lower (p < 0.05) in rolls with 20% added water. NaOH and STPP rolls had higher pH (p < 0.05) than controls (6.28, 6.22, and 6.07, respectively). Panel cohesiveness, juiciness, and acceptability scores were also generally higher (p < 0.05) for NaOH and STPP rolls, compared to controls. There was a high correlation (0.93) between panel cohesiveness scores and instrumental bind values. At 20% added water, STPP rolls were preferred, but at 10% added water, STPP and NaOH rolls were similar in overall acceptability. Thus, if added water level is not too high, NaOH alone or perhaps with other binding agents may be an alternative to phosphates in cooked beef rolls. PMID- 22061138 TI - Quality and bacteriological consequences of beef carcass spray-chilling: Effects of spray duration and boxed beef storage temperature. AB - The effects of water spray-chilling on beef carcass traits and muscle quality, bacteriology and retail case life were determined in a research abattoir. Chilling treatments were compared using 10 crossbred steer carcasses (280 +/- 4 kg) at each spray duration (4, 8, 12 and 16 h) and each vacuum storage temperature (1, 4, 8 and 12 degrees C). Control sides were air-chilled (1 degrees C, 24 h) while spray-chilled sides were sprayed with an intermittent water mist at 1 degrees C in four, 60 s cycles/h for the initial 4-16 h of chilling. The effects of storage temperature were evaluated using vacuum packaged longissimus thoracis (LT) muscle at post-chill intervals of 2, 16, 30 and 44 days. Chilling treatment effects were similar at all spray-chill durations and LT vacuum storage times and temperatures. Carcass spray-chilling did not effect pH, lean colour, % moisture, sarcomere length, shear value or weight loss during the vacuum storage of LT muscle. Carcass fat colour tended to brighten as spray duration was extended up to 12 h, but there was a grey discoloration of fat at spray durations beyond 12 h. Chilling treatment had only marginal effects on anaerobic bacteria during the vacuum storage of LT muscles, or aerobic bacteria during the retail display of rib-eye steaks, and the retail case life of steaks was largely unaffected by spray-chilling. A linear relationship between spray chill duration and carcass weight loss was determined and carcass shrinkage was reduced by 0.08 g/100 g for every hour of spray-chilling. It was estimated that a major beef processing abattoir could utilize spray-chilling to save more than 2000 kg daily in carcass shrinkage, without compromising quality or increasing spoilage losses. PMID- 22061139 TI - The effect of degree of doneness of beef steaks on consumer acceptability of meals in restaurants. AB - A total of 3554 consumers, who selected beef steak menu items at nine restaurants, were surveyed on their attitudes to beef and their assessment of beef steak meals. Consumers were asked to describe the menu item, their assessment of steak size and the degree of doneness of the steak, both as they ordered it and how they perceived it was delivered. Consumers rated the meal for tenderness, taste, overall satisfaction, value for money and intent to repurchase, and were also asked their sex, age and attitude to beef. The average ordered degree of doneness for all consumers was medium. A total of 30% of consumers considered they did not receive their steaks cooked to their ordered degree of doneness. The interaction between ordered and delivered degree of doneness had a highly significant (P < 0.001) effect on consumer scores for tenderness, taste, overall satisfaction, value for money and intent to repurchase. The maximum consumer scores were obtained when steaks were cooked to their ordered degree of doneness. If steaks were perceived not delivered as ordered, there was a decline in all consumer scores (P < 0.001), with a greater penalty for over- than under-cooking (P < 0.001). This study showed the dramatic penalty in consumer satisfaction for a chef failing to deliver a steak cooked to the ordered degree of doneness. PMID- 22061140 TI - Effects of brine ingredients and temperature on cook yields and tenderness of pre rigor processed roast beef. AB - In semimembranosus (SM) muscles removed pre- and post-rigor and injected 10% (wt/wt) with brines formulated to give 2% salt, 1.5% glucose, 0.3% phosphate, 0.15% calcium chloride or 3% sodium lactate in the finished product and cooked within 1 h of injection, cook yields were not significantly affected by processing pre- or post-rigor. Within treatments, however, brine composition had a significant (P < 0.05) effect on cook yields; highest yields were obtained using salt (although this was not significantly different from the water injected control) and lowest yields with calcium chloride. Adding phosphate resulted in lower peak shear force values, and less energy was required to break the sample. The most tender roasts from pre-rigor meat were produced using salt, phosphate or lactate brines and the least tender using calcium chloride. Brine temperature (0 12 degrees C) during injection had little effect on cook yields or tenderness of the roast beef manufactured pre-rigor. The results indicate that accelerated processing of roast beef can result in finished product with acceptable yields and tenderness if salt and phosphate brines are used. PMID- 22061141 TI - Use of lipase from Rhizomucor miehei in dry fermented sausages elaboration: Microbial, chemical and sensory analysis. AB - Three different amounts of lipase (0.075, 0.100 and 0.150 LU/g) from Rhizomucor miehei (Palatase M 200L Novo Nordisk) were used to determine the correct amount to use in dry fermented sausages. Determination of acidity values through fourteen days of ripening showed that 0.100 LU/g was the most appropriate. Two types of fermented sausages were manufactured, addition of the enzyme being the only difference between them. Addition of Palatase did not affect product stability (pH and A(w)), and the growth of micro-organisms. In spite of the increase in acidity value, no rancidity developed as determined by both chemical and sensory analysis. Increases in the liberation of palmitic, palmitoleic, stearic, oleic and linoleic acids were found when lipase was used. Juiciness and taste were slightly better in the sausages with Palatase than in those without, but these differences were not reflected in the overall acceptability. PMID- 22061142 TI - The effect of vacuum and modified atmosphere packaging on the shelf-life of lamb primals, stored at different temperatures. AB - Lamb primals (shoulders) were vacuum packaged or packaged in modified atmospheres containing 80% O(2)/20% CO(2), 50% CO(2)/50% N(2) or 100% CO(2), and stored at 5 or 0 degrees C. They were examined microbiologically at 7 day intervals for total counts obtained under (1) aerobic, (2) CO(2) enriched or (3) anaerobic conditions; B. thermosphacta; pseudomonad and Enterobacteriaceae counts. Off odour assessments were also carried out at these times. In general, there were no significant differences between the total counts obtained from the different incubation conditions in any of the atmospheres. The only exception was noted in 80% O(2)/20% CO(2) at 5 degrees C. Significant differences between atmospheres for the total counts were observed at 0 degrees C only. In the case of B. thermosphacta, the pseudomonads and the Enterobacteriaceae, differences between atmospheres were noted at 5 and 0 degrees C. In general, vacuum packs and 80% O(2)/20% CO(2), and the two high CO(2) atmospheres fell into distinct groups. Storage temperature had a significant effect on all three counts. The relationship between bacterial counts and time was modelled using regression analysis. Data from total counts gave the equations of best fit. Significant differences between atmospheres in terms of off-odour production were observed at 5 degrees C only. The effect of temperature on off-odour production was significant in all atmospheres except 100% CO(2). A scheme was devised based on the growth of different groups of organisms which facilitated comparisons between studies on packaged meats. The results of the present work and that of others are discussed in relation to the different growth patterns which developed with packaging treatments and storage temperature. PMID- 22061143 TI - Comparison of histochemical properties of different pig breeds. AB - The study involved 158 pigs: 51 Hampshire (H), 54 Landrace (L) and 53 Yorkshire (Y). The aim of the study was to compare muscle histochemical properties of M. longissimus dorsi and adductor between muscles from pigs of purebred Hampshire, Landrace and Yorkshire lineages. The following histochemical properties were determined: 1) the percentage of type I, IIA and IIB fibers in number (calculated on the basis of the number of different fiber types) and area (calculated on the basis of the area of different fiber types) as analyzed with the myosin ATPase method using an acid preincubation solution of pH 4.6; 2) the cross sectional area of each fiber type; 3) the percentage of oxidative fibers on the basis of the NADH-TR method; and 4) the capillary density of the muscles. The cross sectional area of type IIB fibers was the largest in Landrace. The highest capillary density (capillaries per mm(2)), 254 +/- 38, was in longissimus of Hampshire. A positive correlation between M. longissimus dorsi and M. adductor was found in the percentage of type I, IIA and IIB fibers in number and area, cross-sectional area of each fiber type, and capillary density. The differences in histochemical properties between breeds were, however, smaller in M. adductor than in longissimus dorsi muscle. In addition, the variation in muscle fiber composition in pigs within the breeds was larger than the average variation between the breeds. PMID- 22061144 TI - Rapid prediction of RN phenotype in pigs by means of meat juice. AB - The dominant RN(-) allele occuring in the Hampshire pig breed is associated with a high glycogen content in glycolytic muscles. To determine the RN phenotype in meat, certain alternative rapid methods were studied. Instead of using whole muscle, meat juice released from post-mortem longissimus dorsi muscle was used in the analyses. Carriers of the RN(-) allele were distinguished from non-carriers on the basis of the concentration of glucose + glucose-6-phosphate (spectrophotometrically determined), glucose only (determined with a rapid assay for blood glucose in diabetic patients) or the osmolality of meat juice. These results were compared with a classification based on the glycolytic potential or the residual glycogen (sum of [glycogen], [glucose] and [glucose-6-phosphate]) in muscle. Higher levels of glucose, of the sum of glucose and glucose-6-phosphate, and of osmolality were found in meat juice from animals of the RN phenotype. The sum of glucose and glucose-6-phosphate in meat juice seems to be a reliable marker for the determination of the RN phenotype in meat. Glucose or the osmolality of meat juice can also be used, but more as a preliminary method. PMID- 22061145 TI - Effect of surface mobility on the uniformity of a thin film under a bubble. AB - The shape of a soap bubble placed on a solid surface is familiar to everyone-a thin hemispherical dome that thickens near the solid surface. This structure is stabilized by the balance between the film's elasticity, provided by surfactant molecules, and the pressure inside the bubble. However, there is also a soap film on the flat solid surface that has been mostly ignored in previous studies; its thickness is typically assumed to be constant or varying monotonically. In this letter, for the first time, we show that the thickness of this film is not always monotonic. Depending on the surfactant type, it can exhibit a significant dip, similar to marginal pinching. This finding has a significant influence in numerous applications in which solid/foam interactions are important, such as oil extraction or foam-based drug delivery. PMID- 22061146 TI - Effect of sodium phytate, sodium pyrophosphate and sodium tripolyphosphate on physico-chemical characteristics of restructured beef. AB - The effects of 0.5% sodium phytate (SPT), sodium pyrophosphate (SPP), and sodium tripolyphosphate (STPP), along with 1% NaCl, on physico-chemical properties of restructured raw and cooked beef were evaluated. In raw beef stored for 1 day at 4 degrees C, the SPT, SPP, and STPP increased pH and salt-soluble protein level and decreased %MetMb and thiobarbituric acid reactive substances (TBARS), compared to the control with salt alone (p < 0.05). In cooked beef, SPT, SPP, and STPP increased bind strength, cook yield, moisture level, and pH, and decreased TBARS (p < 0.05). SPP and STPP increased orthophosphate in both raw and cooked beef (p < 0.05), compared to the SPT and control. SPT, SPP, and STPP decreased the Hunter color L and b values and increased a value in raw beef (p < 0.05) but had no effect on the Hunter color values in cooked beef. The binding value of SPP and STPP were similar over time, and the time to reach maximum binding strength was 10s longer than SPT and 25s longer than the control. These results indicate that SPT compares favorably with traditional phosphates for bind strength and cooked yield, but SPT was slightly more effective than other phosphates for reduction of TBARS 1 day after cooking. PMID- 22061147 TI - Impact of natural sources rich in provitamin a on cooking characteristics, color, texture and sensory attributes of beef patties. AB - Eight ground beef patty formulations, based on replacing meat with a natural source rich in provitamin A (i.e.carrot and sweet potato) were prepared. All treatments displayed better moisture retention than the controls and hence yield was improved. L, a, and b Hunter values increased and Instron texture profile analysis indicated lower peak forces, increased springiness, and, in some cases cohesiveness (i.e. juicier patties) for formulalions with boiled carrot or sweet potato. However, adding these ingredients in a dry form increased hardness, springiness and cohesiveness. Improvement in the content of provitamin A was achieved by incorporating carrot or sweet potato into the patties. Mixing meat with a natural rich source of provitamin A could be a long-term solution for combating vitamin A deficiency. PMID- 22061148 TI - Oxidation of microsomal fraction in the processing conditions of dry-cured ham. The in-vitro effect of brine. AB - Throughout the manufacturing process of dry-cured ham intense lipid oxidation occurs. Muscle microsomal membranes were used as a model of muscle oxidation in three different procedures: (i) enzymic reaction; (ii) nonenzymic reaction and (iii) sarcoplasmic proteins and microsomal fraction interaction. Porcine M. Biceps femoris from normal and PSE meat qualities treated with 3% NaCl at different temperatures was used as a model of the dry-cured ham process. M. Biceps femoris from normal porcine meat was used to study the in-vitro effect of brine in the oxidative processes. Results showed an important increase of MDA concentration in enzymic and nonenzymic reactions and a higher than normal oxidation level in PSE meat in samples aged for 6 days at 4 degrees C. The in vitro assays showed a high level of nonenzymic lipid oxidation at 3 degrees C incubation. On the other hand, the enzymic reaction showed greater values of MDA at 20 degrees C incubation. In-vitro NaCl concentrations seemed to have an antioxidant effect in these conditions. Sarcoplasmic proteins had little effect on the oxidative mechanisms suggesting a lack of interaction of these proteins with the microsomal fraction. PMID- 22061149 TI - Size and location of ice crystals in pork frozen by high-pressure-assisted freezing as compared to classical methods. AB - In high-pressure-assisted freezing, samples are cooled under pressure (200 MPa) to - 20 degrees C without ice formation then pressure is released (0.1 MPa) and the high super-cooling reached (approx. 20 degrees C), promotes uniform and rapid ice nucleation. The size and location of ice crystals in large meat pieces (Longissimus dorsi pork muscle) as a result of high-pressure-assisted freezing were compared to those obtained by air-blast and liquid N(2). Samples from the surface and centre of the frozen muscle were histologically analysed using an indirect technique (isothermal-freeze fixation). Air-blast and cryogenic fluid freezing, having thermal gradients, showed non-uniform ice crystal distributions. High-pressure-assisted frozen samples, both at the surface and at the central zones, showed similar, small-sized ice crystals. This technique is particularly useful for freezing large pieces of food when uniform ice crystal sizes are required. PMID- 22061150 TI - Production and partial characterization of monoclonal antibodies specific to cooked poultry meat. AB - Monoclonal antibodies (MAbs) specific to cooked poultry muscle proteins have been developed for the detection of poultry adulterants in cooked mammalian meat. Saline (0.85% NaCl) extract of heat-treated (100 degrees C, 15min) chicken muscle proteins was used to immunize mice for MAb development. The specificity of MAbs was tested against chicken antigen and protein extracts from seven other meat species (pork, beef, lamb, deer, horse, turkey and duck) by indirect enzyme linked immunosorbent immunoassay (ELISA). The immunogenic components in the poultry protein extracts were determined by SDS-PAGE followed by immunoblotting. A total of six hybridoma cell lines that secrete IgG class MAbs have been developed: MAbs 3E12 and 1A5 were able to distinguish between cooked poultry and mammalian meats, MAbs 9C6 and 6F7 reacted strongly with cooked chicken only, and MAbs, 5D2 and 6G8, reacted with both cooked turkey and chicken but not other species. All six MAbs demonstrated a proportional increased ELISA response to respective adulterated poultry samples in pork over a 0-100% range of aduleration. PMID- 22061151 TI - Concentration of free amino acids and dipeptides in porcine skeletal muscles with different oxidative patterns. AB - Free amino acids and natural dipeptides, have been analyzed in pork muscles having different metabolic type (masseter, trapezius, semimembranosus and longissimus dorsi). Carnosine and anserine showed significantly higher (p < 0.05) concentrations with the glycolytic activity of the muscle while taurine and glutamine were significantly higher in the oxidative muscles. Non-essential free amino acids also showed significant (p < 0.05) increased content in the oxidative muscles. PMID- 22061152 TI - A potential mechanism by which alpha-Tocopherol maintains oxymyoglobin pigment through cytochrome b(5) mediated reduction. AB - The effect of alpha-Tocopherol (alpha-Toc) on the reduction of metmyoglobin (MetMb) was investigated using a liver extract containing cytochrome b(5) (LE) prepared from bovine liver in a Triton X-100 system at 37 degrees C and at pH 7.2, 6.2, and 5.6. The combination of alpha-Toc and LE reduced MetMb at pH 5.6 and pH 6.2 (p < 0.05), but not at pH 7.2. When LE was added, substitution of alpha-Toc with glutathione (0.15MUM) resulted in 13% MetMb reduction, a rate similar to alpha-Toc plus LE (pH 5.6). The addition of NADH and NADPH with LE at pH 5.6 resulted in MetMb reduction of 85% and 25%, respectively, relative to controls. alpha-Toc-mediated reduction at pH 5.6 was further investigated using a purified bovine liver cytochrome b(5) (Cyt b(5)). alpha-Toc effectively reduced Cyt b(5), as indicated by an increased absorbance at 424 nm. The combination of alpha-Toc plus purified Cyt b(5) resulted in a 15% reduction in MetMb at pH 5.6 (p < 0.05) relative to controls. These results suggested a potential reaction whereby alpha-Toc maintains OxyMb via enhancement of Cyt b(5) mediated reduction of MetMb. PMID- 22061153 TI - Amaranthus and buckwheat protein concentrate effects on an emulsion-type meat product. AB - The utilization of Amaranthus (five genotypes) and buckwheat protein concentrates in an emulsion-type meat product comprising beef lean, pork fat, salt and water was studied. 15% of the beef protein was replaced with the protein concentrates and the resulting meat emulsions were evaluated by thermorheology and thermal analysis. The cooking loss and physical properties of the meat gel were determined. The use of Amaranthus and buckwheat protein concentrates considerably affected both the emulsion and the cooked meat gel properties. The most favorable outcome was obtained with the buckwheat protein, which had similar effects to soy proteins. The Amaranthus protein concentrates generally did not give favorable results, although that derived from genotype K112 showed some positive effects. Correlation analysis showed that most of the observed variation in meat product properties could be explained by the emulsifying activity of the protein additive used. PMID- 22061154 TI - Effect of partially replacing dietary barley with 20% carob pulp on post-weaning growth, and carcass and meat characteristics of Comisana lambs. AB - Sixteen male Comisana lambs were divided into two groups of eight at age 45 days. One group received a commercial pelleted diet (control) and the other group (carob) received a diet in which 20% carob pulp was used in partial replacement of barley. The animals were slaughtered at 100 days. No significant differences were observed for live weight, although the carob group ate 14% more dry matter, showing a higher conversion index (2.68 and 3.22kg dry matter per kg weight gain respectively for control and carob). The dressing percentage was higher (p < 0.05) for the control group; however, the carcasses showed no differences in the European classification system. Lightness (lean colour) was the only meat quality parameter (p < 0.05) affected by diet treatment: the carob group lambs had a higher L (*) value. This could not be attributed to ultimate pH, which was not significantly different between the two groups. In triangle tests, sensory panelists were unable to distinguish one diet treatment from the other. Instrumental tenderness was also unaffected by diet treatment. PMID- 22061155 TI - Cryoprotectants for frozen red meats. AB - This present research explores the sensory characteristics of several cryoprotectant carbohydrates that could be added to frozen red meat. The cryoprotectants were sucrose, dsorbitol, maltodextrin DE 24-38 and synthetic polydextrose. The sweetness of aqueous solutions of sorbitol, maltodextrin and polydextrose was compared to standard 0.8% sucrose solution. The relationship between sweetness and cryoprotectant concentration was determined by a sensory panel using the calibration method. The recognition thresholds of cryoprotectants were determined in aqueous solutions and in beef and pork meat by the staircase method. The time course of the sweetness sensation was evaluated in aqueous sucrose, sorbitol, maltodextrin and polydextrose solutions at concentrations corresponding to the concentration of equal sweetness. The data suggest that polydextrose is the cryoprotectant of choice in red meat. Polydextrose was the least sweet; its taste was distinctly suppressed by meat, the duration of sweetness was the shortest one and the total flavour impact, i.e. the total area under the time-intensity curve, was smallest. PMID- 22061156 TI - Effect of dietary alpha-tocopheryl acetate supplementation on alpha-tocopherol distribution in raw turkey muscles and its effect on the storage stability of cooked turkey meat. AB - Day-old turkey chicks (n = 99) were divided at random into three groups (n = 33) and fed diets containing 20 (E20), 300 (E300) and 600 (E600) mg all-rac-alpha tocopheryl acetate per kg feed per day for 21 weeks prior to slaughter. After slaughter, breasts and legs were removed and examined for alpha-tocopherol content. Breast muscle from birds fed the three diets was oven cooked, cooled, sliced and overwrapped. The oxidative and colour stability of the slices was examined. Mean alpha-tocopherol levels in turkey muscle were significantly (p < 0.05) higher in the E300 and E600 groups compared to the control group fed the E20 diet. alpha-Tocopherol levels in the E300 and E600 groups showed that concentrations in leg muscle were significantly (p <0.05) higher than in breast muscle. alpha-Tocopherol levels in leg and breast muscles from birds fed E20 and E600 diets decreased significantly (p < 0.05) during 12 months of frozen (-20 degrees C) storage. TBARS numbers for breast slices from all three dietary groups, cooked both 24 hr after slaughter and following frozen (-20 degrees C * 11 months) storage, increased during refrigerated (4 degrees C) display for 10 days. TBARS numbers for slices produced from meat previously held in frozen storage increased more rapidly than those for meat cooked following slaughter. In both cases, E300 and E600 diets significantly (p < 0.05) suppressed lipid oxidation compared to E20 samples. In general, Hunter a values for meat slices from turkeys fed the E300 and E600 diets were higher than those for meat slices from turkeys fed the E20 diet. PMID- 22061157 TI - Cholesterol content and fatty acid composition of ostrich meat as influenced by subspecies. AB - Two muscles, the m. gastrocnemius and m. iliofibularis, were excised from the left legs of six Red Neck (Struthio camelus massaicus) and six Blue Neck (Struthio camelus australis) ostriches and analysed for lipid and cholesterol content and fatty acid composition. Total lipid (1.43 g 100g ) and cholesterol content (65.63 mg 100g ) did not differ (ps> 0.05) in any muscle between subspecies. Although the percentage of some individual fatty acids differed (p < 0.05), the total percentage of saturated fatty acids and total monounsaturated fatty acids was similar (p > 0.05) between subspecies in both muscles. Although the percentage total polyunsaturated fatty acids was higher (p < 0.05) in Blue Necks (23.78%) than in Red Necks (23.65%) in the m. gastrocnemius, but not (p > 0.05) in the m, iliofibularis, the difference of 0.13% is probably of no practical significance. PMID- 22061158 TI - Effect of preslaughter handling on muscle glycogen level and selected meat quality traits in beef. AB - The ante-mortem and post-mortem glycogen levels in bull muscle were studied to determine their influence on the ultimate pH, cooking loss and shear force. Forty three bulls (13 Holstein, 12 crosses Holstein * Belgium blue, 9 Slovak Pied and 9 crosses Slovak Pinzgauer * Piemontese) were tied, housed and divided in control (A, n = 30) and stressed (B, n = 13) groups before slaughter. At the institute abattoir, the group B animals were mixed and kept overnight. In group A, bulls were slaughtered immediately after arrival at the abattoir. The following values of muscle were determined: (1) glycogen ante mortem from m. semitendinosus (ST) (biopsy technique, Biotech Nitra), (2) glycogen post mortem (1 hr, 3 hr, 48 hr) from longissimus dorsi muscle (LD), (3) ultimate pH, cooking loss and shear force 48 h post mortem. The results show that the glycogen concentrations ante mortem (ST) and 1 hr post mortem (LD) from unstressed animals were similar (p > 0.05). The ante-mortem and post-mortem (1 hr, 3 hr) muscle glycogen concentration were depleted (p < 0.01) in all stressed bulls. Differences between stressed and unstressed animals (p < 0.01) were found in ultimate pH, cooking loss and in shear force (p < 0.05). Significant correlations (p < 0.01) between ante-mortem (ST) and postmortem (LD, 1 hr, 3 hr) muscle glycogen and ultimate pH and cooking loss supported the possibility of using an efficient biopsy technique in combination with a simple method of glycogen estimation (iodide method) to predict metabolic exhaustion (glycogen depletion) and/or dark cutting condition of bulls. PMID- 22061159 TI - Low flow water quality in rivers; septic tank systems and high-resolution phosphorus signals. AB - Rural point sources of phosphorus (P), including septic tank systems, provide a small part of the overall phosphorus budget to surface waters in agricultural catchments but can have a disproportionate impact on the low flow P concentration of receiving rivers. This has particular importance as the discharges are approximately constant into receiving waters and these have restricted dilution capacity during ecologically sensitive summer periods. In this study, a number of identified high impact septic systems were replaced with modern sequential batch reactors in three rural catchments during a monitoring period of 4 years. Sub hourly P monitoring was conducted using bankside-analysers. Results show that strategic replacement of defective septic tank systems with modern systems and polishing filters decreased the low flow P concentration of one catchment stream by 0.032 mg TPL(-1) (0.018 mg TRPL(-1)) over the 4 years. However two of the catchment mitigation efforts were offset by continued new-builds that increased the density of septic systems from 3.4 km(-2) to 4.6 km(-2) and 13.8 km(-2) to 17.2 km(-2) and subsequently increased low flow P concentrations. Future considerations for septic system mitigation should include catchment carrying capacity as well as technology changes. PMID- 22061160 TI - The relationship between tenderness, proteolysis, muscle contraction and dissociation of actomyosin. AB - The right side m. longmissius thoracis et lumborum (LTL) of 18 10-month-old male lambs was injected with the protease inhibitor E-64, and the left side was injected with isotonic saline within 30 min of stunning. Carcasses were hung during chilling by one of three methods; Achilles tendon; pubic symphysis or pubic symphysis with 2-kg weights attached to each hindleg. The LTL section was divided into three portions and aged for either 1, 3 or 7 days. The tenderness, myofibrillar fragmentation and dissociation of extracted actomyosin by pyrophosphate were determined for each portion of LTL. The protease inhibitor increased shear force values by 57%, with a decrease in shear force in the cranial-caudal direction along the LTL. Muscle from Achilles hung carcasses was the toughest. For sarcomere length hanging method had the greatest effect, with muscle from tenderstretched/weighted carcasses having the longest sarcomeres. Injection of an inhibitor caused a significant reduction in myofibrillar fragmentation (P< 0.001) and hanging method and ageing period also significantly affected this characteristic (P< 0.05). Osmolality of samples aged for 1 day was unaffected by any main effect. The amount of actomyosin (mg/g of muscle sample) extracted from muscles injected with the inhibitor was significantly less (P< 0.001) and there was also a significant effect (P< 0.05) of portion on this variable. The relationship between pyrophosphate and the percentage of myosin dissociated from the actomyosin complex was modelled using an exponential function; Y=A - B exp(-kx). Analysis of A, B and k for the 69 samples fitted with an exponential function showed that there was no significant effect (P>0.05) on A and k of any main effect or their interactions. There was, however, a significant effect (P<0.05) of portion on B and also a significant interaction between injection and hanging method (P<0.05). It was found that B did not explain any additional variance in shear force or myofibrillar fragmentation over the main effects and interactions previously found significant. The inhibitor E-64 was effective at preventing tenderisation indicating the role of cysteine proteases in proteolytic degradation. There was no apparent effect of dissociation on tenderness as measured in this experiment and therefore a causal relationship cannot be identified. PMID- 22061161 TI - Production of mortadella: behavior of Listeria monocytogenes during processing and storage conditions. AB - The presence of Listeria monocytogenes in ready-to-eat meat products is cause of concern to the food industry as well as to health authorities. Studies were conducted to evaluate the presence of L. monocytogenes in mortadellas acquired at retail stores and to evaluate the fate of two levels of a L. monocytogenes pool spiked in two different formulations of the product, cooked under commercial conditions and stored at refrigeration (7 degrees C) and room temperature (25 degrees C). Among the samples collected at different retail stores, 26.7% harboured L. monocytogenes. Regarding to the fate of L. monocytogenes in mortadella, periodically, samples were taken and the surviving L. monocytogenes cells in the spiked products were counted by the MPN procedure. Populations of <0.35 MPN/g of L. monocytogenes were found in these samples. It could be concluded that the heat treatment was effective to reduce 3-log of L. monocytogenes independent of formulation or storage conditions. PMID- 22061162 TI - Optical evaluation of factors affecting appearance of bovine fat. AB - Factors affecting the appearance of bovine fat were studied with a spectrophotometer using surface and transmittance optical probes and halogen and mercury lamps. Reflectance minima in the spectra of the fat were mainly derived from beta-carotene and hemoglobin. The presence of deoxy- and met-hemoglobin darkened the fat color. There were wide differences in the transmittance measurements among the white colored fats. The extracted lipid had a lower reflectance than the adipose tissue but the grinding fat had higher reflectance. With ultraviolet light, the adipose tissue had a higher fluorescence, which strengthened the perceived whiteness compared to the extracted lipid. These results showed that the appearance of bovine fat is mainly affected by the absorbance of carotene and hemoglobin derivatives, the reflectance, transmittance, and fluorescence of lipids, and the reflectance and fluorescence of non-lipid components (connective tissue and cell membranes). PMID- 22061163 TI - Calcium ascorbate as a potential partial substitute for NaCl in dry fermented sausages: effect on colour, texture and hygienic quality at different concentrations. AB - A control product (2.6% NaCl) and different treatments with reduced levels of salt (1, 2.3% NaCl; 2, 2.0% NaCl; 3, 1.7% NaCl; 4, 1.4% NaCl) and increased amounts of calcium ascorbate with an equivalent ionic strength to that of the control were assayed. The percentages of reduction of sodium content in relation to the control were 15, 24, 37 and 45% and the supply of calcium was 26, 33, 42 and 50% of the Recommended Dietary Allowance (RDAs established by NRC, US) for treatments 1, 2, 3 and 4, respectively. Partial substitution of NaCl by calcium ascorbate caused higher acidification related with the higher lactic acid bacteria development and probably with the presence of calcium. The instrumental measurement of colour gave rise to some significant differences especially with the highest amount of calcium ascorbate (treatment 4), giving rise to significant higher a* and b* values and lower L* values in relation to the control. Treatments 2, 3 and 4 lead to products with lower hardness and gumminess values than the control. No problems related to the hygienic quality were observed. PMID- 22061164 TI - Effect of erythorbic acid on cooked color in ground beef. AB - Consumers often use the color of cooked ground beef as an indicator of doneness. For safety reasons, it is recommended that the center of ground beef products be heated to 71 degrees C. In some instances beef may appear done before reaching 71 degrees C, a condition termed premature browning (PMB). Ground beef (15% fat), with added erythorbic acid (ERY) at 0.04 and 0.06% was formed into patties, wrapped in oxygen permeable film, and stored in the dark at 4 degrees C. Patties were stored for either 10 h or 58 h and then cooked to internal end point temperatures of 60, 66, 71 or 77 degrees C. Internal cooked color L(*), a(*) and b(*) values were measured. For beef patties stored 10 h, there was no effect of ERY on internal cooked color. After 58 h storage, ground beef with 0.04 and 0.06% ERY had higher a(*) values than controls at 60 degrees C (P<0.05). Beef with 0.04% ERY cooked to an internal temperature of 66 degrees C had higher a(*) values than 0.06% ERY and controls (P<0.05). There was no effect of ERY on color of beef patties cooked to 71 or 77 degrees C. The presence of 0.04% ERY in ground beef patties stored 58 h appeared to maintain red color at internal temperatures of 60 and 66 degrees C. PMID- 22061165 TI - A PCR-based test for species-specific determination of heat treatment conditions of animal meals as an effective prophylactic method for bovine spongiform encephalopathy. AB - Efficiency of animal waste sterilization prescribed by the European Union and Switzerland was verified using a pork-based ELISA and two PCR assays (tRNA(Glu)/cytochrome b specific for vertebrates; bovine species-specific cytochrome b mitochondrial genome). A total of 204 samples of feedingstuffs were analysed including reference materials subjected to known heat treatments. Both ELISA and PCR assays were able to detect poorly heat-treated feedingstuffs if there was enough pork-based material present. The proposed species-specific PCR test, however, showed a higher sensitivity and specificity as it specifically detected bovine material. Nevertheless, the PCR assay will not detect bovine material in properly heat-treated feeds as the DNA is too fragmented. It is, however, very useful as a rapid, sensitive, and specific method for the routine screening of animal meals with regard to prophylaxis of BSE. PMID- 22061166 TI - Effects of dietary magnesium and duration of refrigerated storage on the quality of vacuum-packaged, boneless pork loins. AB - Quality data were initially collected on 78 pork loins from crossbred pigs fed diets containing 0, 1.25 or 2.5% magnesium mica (MM). Loins were then vacuum packaged, and randomly assigned to either 4 or 8 weeks of storage at 2 degrees C. Dietary MM had no (P > 0.05) effect on moisture loss/retention or subjective and objective color measurements. Purge volume increased (P<0.05) and drip loss decreased (P<0.05) as storage time increased. Moreover, longissimus thoracis et lumborum (LM) chops became lighter (P<0.05), redder (P<0.05), and more yellow (P<0.05) during 8 weeks of storage. Although TBARS values increased linearly (P<0.001) during extended storage, LM chops from pigs fed 2.5% MM tended to have lower (P<0.07) TBARS values after 4 weeks of storage than chops from pigs fed 0 and 1.25% MM. After 8 weeks of storage, however, there was a tendency for TBARS values of chops from pigs fed 1.25% MM to be lower (P<0.07) than chops from pigs fed 2.5% MM. Even though feeding swine diets containing MM did not affect color and water-holding capacity of pork loins during storage, the data indicated inclusion of MM in swine diets may retard onset of oxidative rancidity in vacuum packaged pork loins. PMID- 22061167 TI - Aldehyde reactivity with 2-thiobarbituric acid and TBARS in freeze-dried beef during accelerated storage. AB - When lipid oxidation is evaluated in freeze-dried beef, a yellow 450-nm-absorbing pigment develops during the 2-thiobarbituric acid (TBA) assay. TBA analysis and high performance liquid chromatography (HPLC) were applied to measure oxidative changes in salted freeze-dried beef patties (15% fat) initially during storage at 49 degrees C. The TBA pink pigment (lambda(max)=532 nm) was most pronounced in unstored salted freeze-dried beef, and yellow pigment (lambda(max)=450 nm) predominated in stored samples. An in vitro study of TBA reactivity of different aldehydes, known to be secondary lipid oxidation products, showed that alkanals and alk-2-enals favored TBARS(450) formation, while alka-2,4-dienals favored TBARS(532). Values of TBARS(450) from 95 degrees C TBA incubation were lower than those from 25 degrees C incubation (P<0.05), indicating that the yellow chromophore from the aldehyde-TBA complex was less thermally stable than the pink pigment. 5-Hydroxymethyl-2-furfural, an aldehyde produced from Maillard reaction, also produced strong TBARS(450). Propional, butanal and 5-hydroxymethyl-2 furfural (HMF), were tentatively identified in freeze-dried beef during accelerated storage at 49 degrees C, and have the potential to yield TBARS @450. PMID- 22061168 TI - Temporal aspects related to the perception of skatole and androstenone, the major boar odour compounds. AB - Pork fat samples from 50 boars slaughtered at a commercial abattoir were analysed for skatole and androstenone concentrations and grouped within a 3*3 matrix representing low, medium and high levels of the odour compounds. A 10 member sensory panel, screened and trained to recognise and quantify skatole and androstenone odour intensities, was used to verify the human perception of boar odour in these pork fat samples immediately after heating (+/-65 degrees C) and following a cooling period of ten minutes (+/-25 degrees C). Principal component analysis revealed that the sensory panel differentiated the pork fat samples first and foremost on the basis of the presence or absence of androstenone and/or skatole odours and secondly on the character of the androstenone or skatole odour. Evidence of adaptation towards the odour of skatole was shown by a decreased sensitivity over replicates. Sensory perception of boar odour seems to have a temporal character which can be explained by differences in volatilisation (involving both odourant release and retention) of skatole and androstenone, odour synergism and possibly differences in the properties of the fat matrix of different samples. The results suggest that factors influencing volatilisation of skatole and androstenone should also be considered when predicting sensory responses of boar odour. PMID- 22061169 TI - Fatty acid profiles in three stress genotypes of swine and relationships with performance, carcass and meat quality traits. AB - The objective of this study was to investigate differences in adipose tissue fatty acid composition among stress genotypes as well as to determine relationships of those fatty acids with performance, carcass and meat quality traits. Haplotypic analysis of parents and offspring was employed to assign 48 pigs to three stress genotypes of swine. Individual fatty acid profiles were determined on subcutaneous backfat. Stress genotype had a significant effect on the proportions of C14:0 (P<0.05), C16:0 (P<0.10), C16:1 (P<0.05) and C18:0 (P<0.05) fatty acids. After adjusting for stress and gender, there was a negative correlation between backfat thickness and essential fatty acids (linoleic and linolenic) (P<0.001). In contrast, the correlation of loin muscle area with C18:2 (P<0.01) and C18:3 (P<0.001) was positive. The degree of fat firmness was negatively correlated to the proportion of total unsaturated fatty acids (P<0.01). No significant correlations were observed between fatty acid contents and lean meat quality traits. PMID- 22061170 TI - Influence of beef carcass stretching and chilling rate on tenderness of m. longissimus dorsi. AB - Sides of 31 non-stimulated carcasses of young bulls were subjected to the muscle stretching methods Tenderstretch (TS) by pelvic bone suspension or Tendercut (TC) with two skeletal cuts or served as controls by traditional Achilles tendon suspension. The sides were chilled at fast and medium rates, resulting in temperatures of 4-5 and 9 degrees C in the m. longissimus dorsi (LD) at 10 h post mortem. The LDs were examined for sarcomere length, Warner-Bratzler peak shear force and sensory properties after 8 days of ageing at 4 degrees C. At the fast chilling rate, TS and TC increased sarcomere lengths, reduced shear force and improved sensory tenderness of the LDs compared to the controls (P<0.05). At the medium chilling rate, sarcomere lengths increased (P<0.05), but no significant differences were found in shear force or sensory tenderness (P>0.05) of the muscles due to stretching. However, the medium chilling rate was efficient in producing tender LDs without applying muscle stretching methods. TS and TC are feasible alternatives for improving overall tenderness and reducing variation in tenderness of beef LD at cold shortening chilling conditions. PMID- 22061171 TI - Low stress pre-slaughter handling: effect of lairage time on the meat quality of pork. AB - The effect of lairage time on meat quality was investigated when crossbred pigs were subjected to low stress pre-slaughter handling, where pigs were treated in mixed groups of 15 from the farm to group CO(2) stunning, and where electric goads were not used at any time. Two experiments were carried out, one in spring (n=270) using very standardised conditions and one producer, and one in summer (n=630) using a representative randomly chosen sample of producers. In the first experiment three lairage times were used, less than 30 min (average 26 min), 90 min (average 83 min) and more than 150 min (average 170 min) and no showering. The pH and temperature were measured in the m. longissimus dorsi at various times post mortem, and colour (L(*), a(*), b(*)), internal reflectance and drip loss the day after slaughter. Sensory evaluation was carried out on 16 randomly chosen samples from the shortest and longest lairage time groups. Drip loss, pH(ultimate) and internal reflectance were also measured in the m. biceps femoris and pH(ultimate) and internal reflectance in the m. semimembranosus. Finally, pH(ultimate) was measured in the m. semispinalis capitis. In the second experiment only two lairage times were used, less than 30 min (average 17 min) and more than 130 min (average 150 min) and with intermittent showering and only a subset of the meat quality measurements were made. Lairage time had no effect on any of the meat quality parameters measured in experiment 1. In experiment 2 the shortest lairage time led to a higher temperature in the m. longissimus dorsi at 2 min post mortem, a higher drip loss in the m. biceps femoris and higher internal reflectance values in both muscles the day after slaughter. The differences were, however, very small and may have been an effect of showering. PMID- 22061172 TI - Partial purification and characterisation of dipeptidyl peptidase II from porcine skeletal muscle. AB - The purification and study of biochemical properties of dipeptidyl peptidase II (DPP II; EC 3.4.14.2) from porcine skeletal muscle have been carried out in the present work. The purification included ammonium sulphate fractionation and two HPLC chromatographic separations using a Resource-Q anion exchange column. The enzyme was purified 1270 fold, with a 1.6% recovery and was completely separated from DPP IV activity. The pure enzyme displayed one main protein band with a Mr of 58 kDa on SDS-PAGE. Maximum activity was reached at pH 5.5 and 65 degrees C. Those synthetic substrates containing Pro in N-penultimate position were the most efficiently hydrolysed, whereas in the case of peptides, DPP II efficiently hydrolysed both X-Pro- and X-Ala- peptides. The serine peptidase inhibitors PMSF and Pefabloc SC suppressed DPP II activity in a high degree, whereas 3, 4-DCI and cysteine peptidase inhibitors exerted little effect. Alkaline metal salts inhibited the enzyme activity according to the size of the cation, and among the assayed divalent cations, only Cu(2+), Fe(2+) and Hg(2+) showed significant inhibition of the activity. This is the first time that porcine muscle DPP II has been purified and its biochemical characteristics studied. So, these results contribute to improve the knowledge in relation with the proteolytic chain and the generation of flavour characteristics in meat products. PMID- 22061173 TI - Pro-oxidative effects of NaCl in microbial growth-controlled and uncontrolled beef and chicken. AB - Ground beef or chicken breast muscle samples - either pretreated (PT) with 60 ppm chlortetracycline/0.2% potassium sorbate (to control microbial growth) or not pretreated (NPT) - were mixed with 0-5% NaCl and aerobically refrigerated for 0-6 days. NaCl increased 2-thiobarbituric acid-reactive substances (TBARS) values of stored beef and chicken, regardless of pretreatment, with its concentration having a quadratic effect on TBARS. After 3 or 6 days, beef samples were much higher in TBARS content than chicken samples. At each NaCl level, TBARS content increased or tended to increase with storage time for beef (NPT and PT) and PT chicken, but not in NPT chicken. Nonheme iron content in stored NPT and PT beef and PT chicken tended to increase with NaCl concentration. PMID- 22061174 TI - Look over there! Unilateral gaze increases geographical memory of the 50 United States. AB - Based on their specialized processing abilities, the left and right hemispheres of the brain may not contribute equally to recall of general world knowledge. US college students recalled the verbal names and spatial locations of the 50 US states while sustaining leftward or rightward unilateral gaze, a procedure that selectively activates the contralateral hemisphere. Compared to a no-unilateral gaze control, right gaze/left hemisphere activation resulted in better recall, demonstrating left hemisphere superiority in recall of general world knowledge and offering equivocal support for the hemispheric encoding asymmetry model of memory. Unilateral gaze- regardless of direction- improved recall of spatial, but not verbal, information. Future research could investigate the conditions under which unilateral gaze increases recall. Sustained unilateral gaze can be used as a simple, inexpensive, means for testing theories of hemispheric specialization of cognitive functions. Results support an overall deficit in US geographical knowledge in undergraduate college students. PMID- 22061175 TI - Vigabatrin 35 years later - from mechanism of action to benefit-risk considerations. PMID- 22061176 TI - Mechanism of action of vigabatrin: correcting misperceptions. AB - Discovered more than three decades ago, vigabatrin is approved in more than 50 countries as adjunctive therapy for adult patients with refractory complex partial seizures who have responded inadequately to several alternative treatments and as monotherapy for pediatric patients aged 1 month to 2 years with infantile spasms. Contrary to a fairly common misperception, the compound's mechanism of action is very well-characterized in animal models and cell cultures. gamma-Aminobutyric acid (GABA)-ergic synapses comprise approximately 30% of all synapses within the central nervous system, and therein underlies the primary mode of synaptic inhibition. Vigabatrin was rationally designed to have a specific effect on brain chemistry by inhibiting the GABA-degrading enzyme, GABA transaminase, resulting in a widespread increase in GABA concentrations in the brain. The increase in GABA functions as a brake on the excitatory processes that can initiate seizure activity. Despite the short half-life of vigabatrin in the body (5-7 h) and its relatively low concentration in cerebrospinal fluid (10% of the concentration observed in plasma), it has the profound effect of increasing GABA concentration in the brain for more than a week after a single dose in humans. This effect persists steadily over years of vigabatrin administration and results in significant and persistent decreases in seizure activity. Vigabatrin can be effective with once-daily dosing. Because of its specificity, vigabatrin has helped researchers explore the specific mechanisms within the brain that underlie seizure activity. PMID- 22061177 TI - Vigabatrin therapy for refractory complex partial seizures: review of major European trials. AB - Complex partial seizures (CPS) are a form of localization-related seizures associated with serious comorbidities and risks. CPS can be difficult to treat and may remain refractory to treatment with antiepileptic drugs (AEDs). Refractory CPS (rCPS) can be hazardous because of the potential for severe dysfunction and bodily harm, sometimes with fatal consequences. Control of seizure activity is critical to the clinical management of CPS. Vigabatrin is a unique AED approved in both Europe and the United States as adjunctive therapy for adult patients with rCPS who have responded inadequately to several alternative treatments. This review focuses on appropriately controlled studies of vigabatrin conducted in Europe. Several double-blind studies randomized those with rCPS to treatment with vigabatrin vs placebo, and two evaluated durability of response to long-term, open-label vigabatrin. Endpoints included seizure frequency, treatment satisfaction, and adverse events (AEs). Efficacy outcomes demonstrated that vigabatrin add-on therapy significantly reduced the frequency of seizures. Long-term studies indicated durability of response and tolerability of vigabatrin therapy for up to several years. Treatment satisfaction data indicated a preference for vigabatrin vs placebo for both physicians and study participants. Vigabatrin was well-tolerated with generally mild AEs considered common to AEDs. Vision effects were not formally monitored in these studies. In European trials, vigabatrin was efficacious as adjunctive therapy for rCPS. PMID- 22061178 TI - Vigabatrin therapy for refractory complex partial seizures: review of clinical trial experience in the United States. AB - Vigabatrin is an antiepileptic drug used in more than 50 countries as adjunctive therapy for the treatment of refractory complex partial seizures (rCPS) in adults. First approved in the United Kingdom in 1989, vigabatrin was approved for use in the United States by the Food and Drug Administration in 2009. Although most clinical trials of vigabatrin have been conducted in Europe, three major trials, including two pivotal trials, were conducted in the United States. These trials have demonstrated efficacy and tolerability findings similar to those observed from the European trials. Results of the US trials have demonstrated vigabatrin to be an effective and generally well-tolerated therapy for rCPS in adults, with an optimal dosage of 3 g/day for most patients, and an onset of response generally within 2 weeks. This review focuses on the design and results of the three major US trials of vigabatrin in adults with rCPS. PMID- 22061179 TI - Vigabatrin therapy for infantile spasms: review of major trials in Europe, Canada, and the United States; and recommendations for dosing. AB - Infantile spasms (IS) are a unique and severe form of epilepsy associated with poor neurologic and developmental outcomes. The refractory spasms and abnormal electroencephalogram (EEG) patterns associated with the condition are believed to have a progressively detrimental impact. Therefore, rapid and complete control of spasms is the primary goal of treatment. Well-controlled clinical trials in Europe, Canada, and the United States have demonstrated that vigabatrin is efficacious and generally well-tolerated as monotherapy for IS. Several key studies, including pivotal trials that led to United States approval of vigabatrin in 2009, as well as comparative trials of vigabatrin and hormonal treatment, are the focus of this review. All studies assessed spasm cessation - usually as the primary endpoint - and adverse events. Vigabatrin dosages generally ranging from 100 to 150 mg/kg/day demonstrated efficacy to decrease or eradicate spasms and eliminate hypsarrhythmic EEG in patients with newly diagnosed IS. Several studies demonstrated long-term sustainability of spasm freedom with no negative impact on developmental outcomes. Vigabatrin was generally well-tolerated with few severe adverse events. Visual field defects cannot be adequately assessed in infants and young children, so this potential adverse effect was not evaluated in children with spasms. Notably, the time to response with vigabatrin was very rapid, generally occurring within 2 weeks of initial treatment. This allows for early treatment modification as needed. For infants who respond well to vigabatrin, treatment duration up to 6 months appears to be appropriate for realizing spasm freedom while limiting potential risks of adverse events and recurrences. PMID- 22061180 TI - Primer on visual field testing, electroretinography, and other visual assessments for patients treated with vigabatrin. AB - Vigabatrin, an irreversible inhibitor of gamma-aminobutyric acid transaminase, is an antiepileptic drug indicated in the United States as adjunctive therapy for adult patients with refractory complex partial seizures who have responded inadequately to several alternative treatments and for monotherapy treatment of infantile spasms in patients 1 month to 2 years of age. Approval of vigabatrin in the United States was contingent on the implementation of a Risk Evaluation and Mitigation Strategy (REMS) to manage the threat of a progressive, permanent bilateral concentric peripheral visual field defects (pVFDs) that may occur in patients treated with vigabatrin. The REMS is designed to promote compliance with evidence-based recommendations for baseline (within 4 weeks of the start of treatment) ophthalmologic evaluations and ongoing vision monitoring in all patients treated with vigabatrin. In view of the challenges associated with visual field testing in patients with epilepsy and in infants, clinicians must understand the qualitative (pattern of damage), quantitative (degree of damage), electrophysiologic, and adjunctive techniques recommended for monitoring vigabatrin-treated patients. The objectives of ongoing research are to characterize the onset, progression, and risk of developing vision loss during the first year of vigabatrin treatment and to evaluate the potential of noninvasive imaging as a method for monitoring retinal changes corresponding to the pVFD. This article provides an overview of visual field testing procedures and electroretinography, summarizes the clinical characteristics of vigabatrin associated pVFDs, and provides recommendations for visual field and visual electrophysiology testing relevant to both adult and infant patients treated with vigabatrin. PMID- 22061181 TI - Understanding and interpreting vision safety issues with vigabatrin therapy. AB - Vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid (GABA) transaminase. It is effective as adjunctive therapy for adult patients with refractory complex partial seizures (rCPS) who have inadequately responded to several alternative treatments and as monotherapy for children aged 1 month to 2 years with infantile spasms. The well-documented safety profile of vigabatrin includes risk of retinopathy characterized by irreversible, bilateral, concentric peripheral visual field constriction. Thus, monitoring of visual function to understand the occurrence and manage the potential consequences of peripheral visual field defects (pVFDs) is now required for all patients who receive vigabatrin. However, screening for pVFDs for patients with epilepsy was conducted only after the association between vigabatrin and pVFDs was established. We examined the potential association between pVFDs and epilepsy in vigabatrin-naive patients and attempted to identify confounding factors (e.g., concomitant medications, method of vision assessment) to more accurately delineate the prevalence of pVFDs directly associated with vigabatrin. Results of a prospective cohort study as well as several case series and case reports suggest that bilateral visual field constriction is not restricted to patients exposed to vigabatrin but has also been detected, although much less frequently, in vigabatrin-naive patients with epilepsy, including those who received treatment with other GABAergic antiepileptic therapy. We also reviewed published data suggesting an association between vigabatrin-associated retinal toxicity and taurine deficiency, as well as the potential role of taurine in the prevention of this retinopathy. PMID- 22061182 TI - Non-vision adverse events with vigabatrin therapy. AB - Vigabatrin is an effective antiepileptic drug (AED) for the treatment of refractory complex partial seizures (rCPS) and infantile spasms (IS). In clinical trials, vigabatrin was generally well-tolerated with an adverse event profile similar to that of other AEDs. The most common treatment-related adverse events were central nervous system effects, including drowsiness, dizziness, headache, and fatigue, with adjunctive vigabatrin in adults with rCPS, and sedation, somnolence, and irritability with vigabatrin monotherapy in infants with IS. Vigabatrin had little effect on cognitive function, mood, or behavior in a battery of neuropsychologic tests for rCPS. In placebo-controlled clinical trials, the incidence of depression and psychosis, but not other psychiatric adverse events, was greater with vigabatrin than placebo. Intramyelinic edema (IME) was initially identified in rats and dogs and led to a temporary suspension of clinical trials in the United States. IME was subsequently correlated with delays in evoked potential (EP) and increased T(2) -weighted signals on magnetic resonance imaging (MRI). Clinical trials of vigabatrin were allowed to resume after IME was not detected by neuropathologic assessments of autopsy and neurosurgical specimens or by serial EP or MRI assessments in older children and adults receiving vigabatrin. Subsequently, MRI abnormalities characterized by increased T(2) intensity and restricted diffusion were identified in infants treated with vigabatrin for IS. These abnormalities generally resolved with discontinuation of vigabatrin and, in some cases, during continued therapy. The benefit of improved seizure control must be balanced against the potential risks associated with vigabatrin, including abnormal MRI changes and other vigabatrin related safety issues. PMID- 22061183 TI - Balancing clinical benefits of vigabatrin with its associated risk of vision loss. AB - Vigabatrin is an effective and well-tolerated antiepileptic drug (AED) for the treatment of refractory complex partial seizures (rCPS) and infantile spasms (IS), but its benefits must be evaluated in conjunction with its risk of retinopathy with the development of peripheral visual field defects (pVFDs). Vigabatrin should be considered for rCPS if a patient has failed appropriate trials of other AEDs or is not a suitable candidate for other AEDs, is not an optimal surgical candidate, and continues to experience debilitating effects from seizures. Vigabatrin is indicated as monotherapy for pediatric patients with IS. Its efficacy in achieving improved seizure control should be apparent within 12 weeks in patients with rCPS and within 2-4 weeks after attaining appropriate dosage for patients with IS. Because 12 weeks is well less than the known time of onset of visual defects, the risk of developing pVFDs may be minimized by discontinuing vigabatrin early during the course of therapy for patients with inadequate response. Appropriate vision screening is recommended at baseline, every 3 months during continued vigabatrin treatment, and at 3-6 months after discontinuation (if therapy has spanned more than a few months). If a pVFD is detected at any point and the decision is made to discontinue therapy, the pVFD is not likely to progress after discontinuation of vigabatrin. Although some patients will be at risk of retinopathy, vigabatrin is an appropriate treatment option for patients who achieve substantial clinical benefit, especially given the severe consequences of rCPS and uncontrolled IS. While retinopathy with the development of pVFDs is a serious adverse event, it is not life-threatening and its risk can be effectively managed. PMID- 22061184 TI - Anti-amyloidogenic and fibril-destabilizing effects of two manganese-salen derivatives against hen egg-white lysozyme aggregation. AB - Amyloid depositions of proteins play crucial roles in a wide variety of degenerative disorders called amyloidosis. In the present study, we used hen egg white lysozyme (HEWL), as an in vitro model system, to induce fibrillation under high temperatures and acidic pH conditions, and investigated the inhibitory and disruptive effects of two salen-manganese complexes, namely EUK-8 and EUK-134, with aromatic structures, against fibrilization. Results of this study showed that EUK-8 and EUK-134 in a dose-dependent manner inhibited the HEWL aggregation. Similar results were obtained when these compounds were added to pre-formed amyloid fibrils. Docking results also demonstrated that the aromatic rings of EUK 8 and EUK-134 interact with the hydrophobic region of lysozyme via Van der Waals interactions. Results of MTT assay indicated that addition of pre-formed fibrils treated with EUK-8 and EUK-134 at doses 1:1 and 5:1mM; drug to protein, to SK-N MC cells significantly increased the viability of cells, compared to the fibril sample alone. Based on these results, it might be concluded that in addition to inherent hydrophobicity associated with the ligand section of each of the derivatives, electron density around the central metal ion of the derivatives contributes to lower lysozyme fibril accumulation. PMID- 22061185 TI - Polyunsaturated fat and fish oil in diets for growing-finishing pigs: effects on fatty acid composition and meat, fat, and sausage quality. AB - Forty-eight crossbred growing-finishing pigs were used to study the effects of polyunsaturated fatty acids (PUFA 31%= low and 50%= high) and fish oil (0, 0.2, and 0.4% capelin) diets on fatty acid composition, chemical traits, and sensory properties of the longissimus muscle, fat, and sausages. High levels of PUFA, independent of the level of fish oil, increased oxidation and rancidity for whole muscle (stored at 1 and 8 months at -23 degrees C) and sausages (TBARS 0.6-1.3). Fish oil at 0.4% in the diet increased TBA values of loin, but did not affect sensory evaluation scores. An interaction between PUFA and fish oil occurred for TBARS values and rancid odour in sausage, where the 0.4% fish oil and high PUFA level showed highest oxidation (TBARS 1.9). Although fish oil and high PUFA levels might contribute to a more healthy meat, their undesirable affects on palatability would limit their use. PMID- 22061186 TI - Effect of tocopherol concentration on rancidity development during frozen storage of a cured and an uncured processed pork product. AB - This research evaluated the effect of addition during processing of various concentrations of tocopherol (0-1000 mg/kg) on the subsequent lipid oxidation and rancidity development during frozen storage of two pork products-a coarsely ground cured sausage and an uncured restructured pork roast. The results indicated that tocopherol had little effect on lipid oxidation, as measured by TBARS values and sensory evaluation during frozen storage at -18 degrees C for 37 weeks for either product. However, lipid oxidation only occurred to a limited extent even in products without tocopherol and was insufficient to cause rancid flavour development. It was, therefore, not possible to determine if tocopherol added during processing was effective as an antioxidant in preventing lipid oxidation in processed pork products during frozen storage. PMID- 22061187 TI - Palatability of bison semimembranosus and effects of marination. AB - The present study was conducted to investigate the palatability of bison semimembranosus muscle (SM) and the effects of injection with sodium chloride and sodium tripolyphosphate on cooking yield, colour, shear force and consumer acceptability. Twenty paired SM were obtained from 10 intact male bison (aged 24 30 months); each of these muscles was divided longitudinally into two sections. One section was injected to 110% of its original weight to contain 0.5% sodium chloride and 0.3% sodium tripolyphosphate, while the other was kept as a non injected control. HunterLab a* (redness) and b* (yellowness) values did not differ (P>0.05) between injection treatments; however, injected steaks had lower L* values (darker) compared to controls. Control samples from bison SM were very lean and high in protein but not very tender. Marination by injection was able to significantly reduce shear force values of SM; that is, injected steaks/roasts had significantly (P<0.001) lower shear force values (63.9 N) compared to control samples (102.3 N). Cooking yields for the steaks/roasts from the injected sections were significantly (P<0.001) higher compared to those from control non injected sections when cooked to either 71 or 77 degrees C. Bison samples cooked by moist-heat had significantly (P<0.001) lower cooking losses and shear force values compared to those cooked by dry-heat. As expected, steaks/roasts were more tender and had higher cooking yields when cooked to a medium level of doneness (71 degrees C) compared to an internal temperature of 77 degrees C (well done). A panel of 80 consumers preferred injected steaks cooked to 77 degrees C endpoint over other combinations, followed by non-injected steaks cooked to 71 degrees C, whereas injected steaks cooked to 71 degrees C and non-injected steaks cooked to 77 degrees C were equally but least preferred. Hence, injection seems to be protecting against moisture loss at high end-point cooking temperatures. PMID- 22061188 TI - Effects of sodium chloride and lactates on chemical and microbiological changes in refrigerated and frozen fresh ground pork. AB - Changes in fat oxidation and color of freshly ground pork, 14% fat, during storage at 2 degrees C for 15 days and at -20 degrees C for up to 70 days were determined. The fresh meat was further treated with NaCl (1 and 2%, by weight), sodium or potassium lactate (2%), and combinations of NaCl and lactates. The microbial stability of the refrigerated meat was enhanced by the lactates, and their combinations with NaCl were more effective than lactates alone in delaying the onset of spoilage. Changes in TBARS were seen in the untreated meat only after it was judged spoiled when stored at 2 degrees C (day 7), and after 69 days at -20 degrees C. Among treatments, fat stability was highest in lactate treated meat, and TBARS values were generally similar to those in untreated meat. NaCl enhanced fat oxidation, and the effects of 2% salt were significantly higher than those of 1% (P<0.05). Combinations with lactates reduced the prooxidant effects of NaCl at both storage temperatures, and the effects were more pronounced in meat with 2% NaCl stored at -20 degrees C. The red color (a* value) was enhanced by NaCl and lactates immediately after their addition to the meat. However, values for all treatments, including the untreated meat, declined rapidly after 4 days at 2 degrees C, and were 50-70% lower than the initial values after 8 days. Color stability in the frozen meat was highest in control and lactate-treated samples throughout the storage period. It was lowest in samples with 2% NaCl, whether alone or in combination with lactates. Sodium or potassium lactate (2%) enhanced the microbial stability of refrigerated pork without deleterious effects on its color or fat stability. Combinations of lactates with NaCl improved the fat stability, particularly during storage at -20 degrees C, by reducing the prooxidant activity of NaCl. PMID- 22061189 TI - Evaluation of shelf life of cured, cooked, sliced turkey fillets and cooked pork sausages-'piroski'-stored under vacuum and modified atmospheres at +4 and +10 degrees C. AB - Evaluation of shelf life was made of cured, cooked, sliced turkey breast fillets and a type of cooked pork sausage called 'piroski', stored in vacuum and in six different modified atmospheres (MA) at +4 and +10 degrees C. Total viable count, lactic acid bacteria, pH changes, colour attributes and the presence of pathogenic bacteria (listeriae, staphylococci) were monitored during the storage. The results of the study showed that the average shelf life for both products was 2 and 1 week at 4 and 10 degrees C, respectively. By the end of these periods, the bacterial population consisting of only lactic acid bacteria reached 10(8) cfu g(-1). Macroscopical (colour, drip loss and slime) and organoleptical changes (sour odours) were not related to pH and observed already at pH values >5.5. It is concluded that the use of MA packaging in these tests did not extend and not reduce the product shelf life in comparison to vacuum packaging. PMID- 22061190 TI - Microbiological quality of retail chicken by-products in Spain. AB - The microbiological quality of retail chicken parts (legs, wings and giblets) and processed chicken products (hamburgers and sausages) in Spain was investigated. Mean counts (log(10) cfu/g) ranged from 5.56 to 7.28, 5.96 to 7.87, 3.49 to 5.42, 2.60 to 4.33 and 2.47 to 3.48 for mesophiles, psychrotrophs, coliforms, Escherichia coli and Staphylococcus aureus, respectively. Chicken parts were generally regarded as being of unacceptable quality, since psychrotrophs, E. coli and S. aureus counts were higher than the maximum limits established in the guidelines for poultry meat. On the basis of Spanish Microbiological Standards, 80% of the samples of hamburgers and sausages were also regarded as being of unacceptable quality. The main reason for the lack of acceptability was excessive counts of mesophiles. The results in this study indicate that chicken by-products (especially those made with ground meat) could represent notable hazards to humans and are a cause of public health concern. PMID- 22061191 TI - Effect of dietary vitamin E, fishmeal and wood and liquid smoke on the oxidative stability of bacon during 16 weeks' frozen storage. AB - Twelve (Large White*Landrace) gilts were randomly allotted in a 2*2 factorial design with the respective factor being dietary vitamin E (10 or 200 mg/kg feed) and dietary fishmeal (0 or 5%). Bacon was manufactured from the meat obtained from the animals after slaughter using wood smoke only or a combination of liquid and wood smoke. The oxidative stability of the bacon was examined over 16 weeks of frozen storage. Lipid oxidation in the product was measured by means of thiobarbituric acid reactive substances (TBARS) and fluorescence shift. Dietary fishmeal supplementation increased lipid oxidation in bacon, while dietary vitamin E supplementation reduced lipid oxidation in the product. Lipid oxidation in frozen bacon was successfully reduced when bacon was manufactured from pigs fed a diet supplemented with or without 200 mg of alpha-tocopherol per kilogram of feed and processed with a combination of liquid and wood smoke. It is concluded that bacon processed with a combination of liquid and wood smoke was significantly less (P<0.001) susceptible to lipid oxidation than bacon processed with wood smoke only. PMID- 22061192 TI - Quantitative determination of titin and nebulin in poultry meat by SDS-PAGE with an internal standard. AB - The method of quantitative determination of titin and nebulin in chicken meat by SDS-PAGE electrophoresis technique was developed by application of beta galactosidase as the internal standard. The method was tested first on marker protein samples of known concentrations (myosin, transferrin, glutamic dehydrogenase) and then the method was used in the determination of titin and nebulin content in chicken meat. The method demonstrated high accuracy, confirmed by correlation coefficient 0.91/0.99. Two gel analysis techniques, i.e. scanning and densitometry were also compared. By the use of marker proteins as well as titin and nebulin, higher accuracy and precision were achieved in scanning than in the densitometric technique. Recoveries of three marker proteins were between 93 and 102% for the technique of the scanning of the gel and between 99 and 116% for the densitometry. PMID- 22061193 TI - Sensory characteristics of Galician chorizo sausage packed under vacuum and under modified atmospheres. AB - One of the most widely used methods for conservation of Galician chorizo sausage is vacuum packing. Recently, some manufacturers have begun to implement packaging under modified atmospheres. We compared the sensory characteristics, over about 7 months of storage, of chorizos packed under vacuum or under a modified atmosphere (100% CO(2), 100% N(2), or 50:50 CO(2)/N(2)). Most of the 29 variables considered differed significantly between samples packed under vacuum and samples packed under the modified atmospheres. Nineteen of the variables varied significantly over the storage period. Parallel studies of gas permeabilities confirmed that the aluminum-polyester-polyethylene laminate used for packing under modified atmospheres showed very low permeability to both CO(2) and N(2). PMID- 22061194 TI - Contents of vitamins B(1), B(2), B(6), and B(12) in pork and meat products. AB - The concentration of B vitamins (B(1), B(2), B(6), and B(12)) was determined in three pork muscles (Longissimus dorsi, loin; Biceps femoris, ham; and Triceps brachii, shoulder) and in pork and other meat products (cooked, pickled, and cured), of importance because they are consumed in high quantities. The results were compared with values reported by other authors and their contribution to the daily intake of these vitamins estimated. This showed that pork provides, on average, 97, 25.8, 35/43.7 (men/women), and 37% of the RDA (Recommended Dietary Allowances) for vitamins B(1), B(2), B(6), and B(12), respectively. PMID- 22061195 TI - Verification of different glial fibrillary acidic protein (GFAP) analyses as accurate detectors of central nervous system tissue in advanced meat recovery (AMR) products. AB - A glial fibrillary acidic protein (GFAP) fluorescent enzyme linked immunosorbant assay (ELISA) was compared with an ELISA test kit for GFAP to determine the level of central nervous system (CNS) tissue in advanced meat recovery (AMR) products. The test kit results were highly correlated (r=0.975) with the fluorescent ELISA. Meat cuts and AMR were analyzed on site at 14 meat plants utilizing the test kits. In seven of the plants all AMR samples had less than 1 ng GFAP. Seven of the plants had greater than 1 ng GFAP in AMR samples. Development of proper process controls to eliminate inclusion of spinal cord in AMR materials should bring all values to less than 1 ng GFAP, a level slightly above background. PMID- 22061196 TI - The microbiological quality of beef tripe using different processing techniques. AB - The microbiological quality of routinely processed tripe and rumen pillars were compared with those derived after emptying the rumen (paunch) without using water (dry dumping) and after deliberately bursting the paunches before processing. Prior to packing the mean log(10) aerobic plate counts (APC) for the routinely processed tripe and rumen pillars were 3.55+/-1.08 and 3.28+/-0.87/g respectively. The corresponding mean log(10) total coliform counts (TCC) were 1.27+/-1.28 and 2.08+/-0.87. The mean log(10) APC counts on tripe and rumen pillars after dry-dumping were 3.06+/- 0.60 and 3.90+/- 0.75/g, respectively. The corresponding mean log(10) TCC were 1.03+/- 0.60/g and 2.75+/- 1.14/g respectively. After deliberately bursting the paunches, before processing, the mean log(10) APC counts on tripe and rumen pillars were 3.55+/-0.83/g and 3.50+/- 0.59/g and the mean log(10) TCC were 1.54+/- 0.95/g and 2.66+/- 0.82/g respectively. In all cases the prevalence of Salmonella and Campylobacter spp. was less than 3%. The results indicate that both tripe and rumen pillars can be produced after dry dumping without compromising the quality of tripe and rumen pillars. Similarly, incidentally burst paunches that become contaminated with ingesta on the serosal surface can be processed without compromising product quality. PMID- 22061197 TI - Effect of feeding pasture-finished cattle different conserved forages on Escherichia coli in the rumen and faeces. AB - The effects of eight different pre-slaughter diets on gut microflora, pH and dry matter were evaluated in 112 slaughter-weight, pasture-finished heifers. Hide dirtiness at slaughter, plasma cortisol, meat pH and stickiness, and liveweight loss, were also examined. The pre-slaughter diets were: 48 h of 100% meadow hay, lucerne hay, red clover hay, perennial ryegrass hay, haylage, haylage supplemented with maize silage, pasture, or 24 h fasting before transport. Fasted animals had the highest counts of rumen Escherichia coli and Enterobacteria compared to other treatments (P<0.001), while red clover hay and haylage had the lowest (P<0.05). Faecal E. coli counts were also highest for fasted animals (P<0.05). Rumen E. coli and Enterobacteria counts were positively correlated with rumen pH (P<0.001), and negatively correlated with fibre intake (P<0.001). Diet significantly affected the pH of both the rumen and faeces (P<0.001), with fasted animals having the highest rumen pH and haylage and red-clover hay-fed animals the lowest. Dry matter (%) of the rumen contents was also significantly affected by diet (P<0.001). The mean carcass weight of fed heifers was 5 kg heavier than that of the fasted heifers (P<0.05). A pH/volatile fatty acid (VFA) dependent mechanism is suggested as the major mode for E. coli suppression by feeds used in the study. Coumarins may have contributed to lower ruminal and faecal E. coli counts with E. coli counts negatively correlated with expected coumarin ingestion (P<0.01). Feeding pasture-fed cattle conserved herbaceous forages, in preference to fasting, before transport for slaughter may prove beneficial in reducing the risk of carcass contamination with E. coli and other bacteria of digesta and/or faecal origin, and in protecting carcass weight. PMID- 22061198 TI - Heating method and final temperature affect processing characteristics of beef semimembranosus muscle. AB - The effect of thawing and cooking regimes on the processing characteristics and colour of cooked roast beef made from frozen beef cap-on inside round (semimembranosus, adductor and gracilus muscle) was investigated. After thawing in air or water, the cap was removed and the insides were pumped (110%), tumbled (30 min continuously) and then cooked in either constant-temperature water baths or baths where a 10 degrees C difference was maintained between the roast and the water to an internal temperature of 63 or 80 degrees C. Purge was higher for insides thawed in air. Insides that were cooked at a constant temperature had higher cook yields the same was seen for lower end-point temperatures. Colour of raw insides thawed in water was slightly redder than insides thawed in air. Thawing and cooking regime did not affect the colour of cooked slices but the higher the end temperature, the higher the Hunter L and the lower the Hunter a and b values. Data from this research suggests that roast beef manufacturers should evaluate thawing and cooking procedures to ensure they optimize their process. PMID- 22061199 TI - Post mortem energy metabolism and meat quality of porcine M. longissimus dorsi as influenced by stunning method - A (31)P NMR spectroscopic study. AB - Post mortem changes in phosphorus metabolites and pH were studied in M. longissimus dorsi from pigs (n=10) stunned either by CO(2) (n=3), electrical (n=2), captive bolt pistol (n=2) or by anesthesia (ketamine) (n=3). (31)P-NMR spectroscopy revealed significant effects of stunning method on changes of the various phosphorus metabolites in the muscle post mortem, with the effect being most pronounced on the degradation of phosphocreatine (PCr). Moreover, the four stunning methods gave rise to large differences in the progress of pH as determined by (31)P-NMR spectroscopy. Using anesthesia as the reference showed that the captive bolt pistol caused the highest rates of post mortem degradation of phosphorus metabolites, electrical stunning intermediate, and CO(2)-stunning causing the lowest post mortem degradation rates, even though CO(2)-stunning also was associated with higher post mortem degradation rates compared with anesthesia. Finally, it was demonstrated that the water-holding capacity (WHC) of the meat was affected by the applied stunning method, as CO(2)-stunning, electrical stunning and captive bolt pistol resulted in mean drip losses of 6.4, 8.3 and 8.6%, respectively (P=0.02). The result displays the significance of induction and progress in post mortem changes on WHC in meat. PMID- 22061200 TI - Meat and storage effects on processing characteristics of beef roasts. AB - Two experiments were done to determine the effect of storage conditions and meat cut on the processing characteristics of beef roasts. The first experiment examined the effect of storage condition (fresh/frozen), cap on/off, thawing regime and holding time post thawing on purge, brine uptake, cook yield and colour of raw and cooked roasts. The second experiment examined the effect of meat cut (insides/flats) and chilled storage for up to 8 weeks on processing characteristics of roast beef. Purge was greater for insides stored frozen without cap and air thawed. Frozen thawed cuts had increased brine retention after injection, after tumbling and after cooking. Flats had less purge and higher cook yields when manufactured into roast beef. Raw and cooked colour was not significantly affected by most factors investigated. Raw meat was more red than meat that had been frozen. PMID- 22061201 TI - Proteolytic activity of Penicillium chrysogenum and Debaryomyces hansenii during controlled ripening of pork loins. AB - The role of micro-organisms on the ripening process of dry-cured ham, particularly with respect to proteolysis, is not clear. This is partially due to the lack of an adequate system to study changes on a sterile control meat product for long ripening times. Using a meat system based on sterile pork loins ripened under aseptic conditions for 106 days, the contribution to the proteolysis of two micro-organisms isolated from dry-cured ham has been established. Changes were studied by SDS-PAGE of sarcoplasmic and myofibrillar proteins, capillary zone electrophoresis (CZE) of low ionic strength-soluble nitrogen compounds, and HPLC of free amino acids. Debaryomyces hansenii Dh345 did not show any significant proteolytic activity. However, Penicillium chrysogenum Pg222 showed high proteolytic activity on myofibrillar proteins resulting in an increase in soluble nitrogen compounds. For this, P. chrysogenum Pg222 should be considered to be used as starter culture in meat products made using long ripening times. PMID- 22061202 TI - Cell-autonomous and non-cell-autonomous toxicity in polyglutamine diseases. AB - Polyglutamine diseases are neurodegenerative disorders caused by expansion of polyglutamine tracts in the coding regions of specific genes. One of the most important features of polyglutamine diseases is that, despite the widespread and in some cases ubiquitous expression of the polyglutamine proteins, specific populations of neurons degenerate in each disease. This finding has led to the idea that polyglutamine diseases are cell-autonomous diseases, in which selective neuronal dysfunction and death result from damage caused by the mutant protein within the targeted neuronal population itself. Development of animal models for conditional expression of polyglutamine proteins, along with new pharmacologic manipulation of polyglutamine protein expression and toxicity, has led to a remarkable change of the current view of polyglutamine diseases as cell autonomous disorders. It is becoming evident that toxicity in the neighboring non neuronal cells contributes to selective neuronal damage. This observation implies non-cell-autonomous mechanisms of neurodegeneration in polyglutamine diseases. Here, we describe cell-autonomous and non-cell-autonomous mechanisms of polyglutamine disease pathogenesis, including toxicity in neurons, skeletal muscle, glia, germinal cells, and other cell types. PMID- 22061203 TI - Participation in physical play and leisure: developing a theory- and evidence based intervention for children with motor impairments. AB - BACKGROUND: Children with motor impairments (e.g. difficulties with motor control, muscle tone or balance) experience significant difficulties in participating in physical play and leisure. Current interventions are often poorly defined, lack explicit hypotheses about why or how they might work, and have insufficient evidence about effectiveness. This project will identify (i) the 'key ingredients' of an effective intervention to increase participation in physical play and leisure in children with motor impairments; and (ii) how these ingredients can be combined in a feasible and acceptable intervention. METHODS/DESIGN: The project draws on the WHO International Classification of Functioning, Disability and Health and the UK Medical Research Council guidance for developing 'complex interventions'. There will be five steps: 1) identifying biomedical, personal and environmental factors proposed to predict children's participation in physical play and leisure; 2) developing an explicit model of the key predictors; 3) selecting intervention strategies to target the predictors, and specifying the pathways to change; 4) operationalising the strategies in a feasible and acceptable intervention; and 5) modelling the intervention processes and outcomes within single cases. DISCUSSION: The primary output from this project will be a detailed protocol for an intervention. The intervention, if subsequently found to be effective, will support children with motor difficulties to attain life-long well-being and participation in society. The project will also be an exemplar of methodology for a systematic development of non-drug interventions for children. PMID- 22061204 TI - Influence of volatile compounds on the development of off-flavours in pig back fat samples classified with boar taint by a test panel. AB - Dynamic Head Space methodology was applied to evaluate the possible contribution of some volatile compounds to the development of boar taint in pig backfat samples with low concentrations of skatole and androstenone, but which had previously been classified as tainted by a trained test panel. Volatile compounds were collected in a trap of graphited charcoal and analysed by GC-MS in Scan mode. Aldehydes and short chain fatty acids, compounds that play a significant role in the development of undesirable aromas in food products, were the main classes of compounds identified in this study, although the possible contribution of other compounds that were detected in a minor proportion - such as alcohols and ketones - was evaluated. Styrene and 1,4-dichlorobenzene, compounds that may have come from an external contamination, showed a high concentration in the samples classified with boar taint, so these compounds could have been responsible for the development of some off-flavours in the fat samples studied in this work. In the same study, skatole and androstenone were also determined by normal phase HPLC and GCMS, respectively. PMID- 22061205 TI - Effect of gamma-irradiation on the sensory quality of moist beef biltong. AB - Moist beef biltong (mean moisture content=46.7% and a(w)=0.919) was vacuum packaged and irradiated to target doses of 0, 2, 4, 6, and 8kGy. Thiobarbituric acid reactive substance (TBARS) measurements and sensory difference and hedonic tests were performed to determine the effect of gamma-irradiation on the sensory quality of the biltong. TBARS values only increased significantly (P<0.05) if biltong was irradiated to at least 8kGy, indicating a low degree of lipid oxidation. This can be attributed to the low fat content (on average 1.53%) of the biltong used in this study, as well as irradiation under vacuum conditions. All irradiated samples could be discriminated (P<0.05) from non-irradiated biltong, but none was rated as less acceptable. Dissipation of volatiles before tasting (by exposing the product to aerobic conditions before consumption), a low degree of lipid oxidation and liking of distinct 'irradiation flavours' possibly all attributed to the flavour of irradiated biltong not being regarded as unacceptable compared to controls. Biltong irradiated at 2 and 4kGy was however liked significantly more (P<0.05) than other samples, indicating that slight, non oxidative irradiation-induced flavour changes may contribute to flavour development in the usually more bland moist beef biltong. Although lean moist beef biltong can thus be irradiated to doses up to 8kGy without adversely affecting the sensory acceptability, low dose irradiation (?4kGy) is most feasible to optimise the sensory quality. PMID- 22061206 TI - Changes of alanyl aminopeptidase activity and free amino acid contents in biceps femoris during processing of Jinhua ham. AB - Sixty experimental Jinhua hams were processed by a traditional method. The potential alanyl aminopeptidase (AAP) activity in biceps femoris was determined. The effects of temperature, salt content, sodium nitrate content and pH on muscle AAP were evaluated using response surface methodology. Porcine muscle was found to possess very strong potential AAP activity that decreased gradually during processing from 201,635Ug(-1) before salting to 6147Ug(-1) after aging. Temperature, pH and salt content had significant exponential effects on AAP activity (P<0.001). Both temperature and salt content interacted with pH in their effects on AAP activity (P<0.01). However, 0-50mgL(-1) sodium nitrate had no detectable effect on AAP activity (P>0.05). The regression model showed muscle AAP maintaining its activity all through Jinhua ham processing, indicating that muscle AAP may generate free amino acids during the processing and storage of Jinhua ham. The concentrations of free amino acids increased significantly (P<0.05) during Jinhua ham processing, except for arginine and cystine. The concentrations of most free amino acids were 5-20 times higher in the final product than in hams before salting. Final concentrations exceeded thresholds for sensory detection, thus implicating an important role of free amino acids in the determination of Jinhua ham flavor. PMID- 22061207 TI - Determination of the sensory attributes of a Spanish dry-cured sausage. AB - A lexicon for describing the sensory attributes of a Spanish dry-cured sausage (salchichon) was developed in order to characterise this product. A highly trained, descriptive sensory panel generated, defined, selected and referenced the main sensory characteristic of commercial salchichon elaborated from meat of white pig. This language was not only descriptive but also discriminative. Panellists initially produced a vocabulary of 108 terms that were later modified to 15 attributes: four for appearance (luminance, presence of crust, fat/lean connection and exudate); four for odour (black pepper, lactic acid, mould and other spices); two for texture (hardness and initial juiciness) and five for flavour (black pepper aroma, mould aroma, other spices aroma, acid taste and salty taste). The Kruskal-Wallis test showed that all attributes were significantly different between samples (p<0.001). Three different groups of Salchichones were separated by principal component analyses: group I was characterised by strong other spices smell and aroma and higher juiciness than the other groups. Salchichones from group II had a high mould smell and aroma, a notable fat/lean connection and exhibited a great amount of exudate. Salchichones from group III were characterised by an acid and salty taste. PMID- 22061208 TI - Genotype and gender differences in carnosine extracts and antioxidant activities of chicken breast and thigh meats. AB - The aim of this work was to investigate the effects of genotypes and gender of chickens on carnosine contents and their antioxidant activities. The carnosine content of fresh meat from Thai indigenous and hybrid native chickens differed between breeds (p<0.01) and genders (p<0.01). Regardless of these differences, breast meat contained 2-4-fold higher carnosine than thigh meat. After water and heat extraction at 80 degrees C and ultrafiltration, the carnosine content of meat extracts had the same distribution as in fresh meat. No relationship between total iron and carnosine content on antioxidant activity of the extract was detected. However, when compared in the extracts on the basis of mM carnosine in oxidation system, the extracts of chicken meat showed greater antioxidant activity than pure carnosine (p<0.05). Furthermore, at equal concentrations, thigh meat extract had higher effective inhibiting ability than breast extract. PMID- 22061209 TI - Technological activities of Staphylococcus carnosus and Staphylococcus simulans strains isolated from fermented sausages. AB - The aim of this study was to determine the technological properties of 2 strains of Staphylococcus simulans (Ssm12, Ssm21) and 4 strains of S. carnosus (SC28, SC31, SC54 and SC55) for the selection of a potential starter cultures to employ in the processing of dry fermented sausages. The strains were studied to evaluate nitrate reductase, proteolytic, lipolytic, decarboxylase and antioxidant activities as well as growth ability at different temperatures, pH and NaCl concentrations. Nitrate reductase activity was determined at 15, 20 and 30 degrees C. By spectrophotometric method all the strains were able to reduce nitrate to nitrite at the different temperatures but these results were not confirmed by the agar plate method. Antioxidant and lipolytic activities were evaluated by spectrophotometric assay. All the strains showed antioxidative enzymes superoxide dismutase (SOD) and catalase whereas all appeared unable to hydrolyse pork fat. Proteolytic activity was determined by agar plate method, spectrophotometric assay (OPA) and sodium dodecyl sulphate gel-electrophoresis (SDS-PAGE) and all strains appeared to be able to hydrolyse sarcoplasmic proteins but not myofibrillar proteins. Finally, all the strains grew at 15 and 20 degrees C, in presence of 10%, 15% and 20% of NaCl and at pH 5.0 and 5.5 and were unable to produce histamine, cadaverine and putrescine. The results showed that all strains studied possess useful technological activities that would make them eligible as a good starter cultures for fermented sausages. PMID- 22061210 TI - Effect of feeding partially hydrogenated lard on trans-fatty acid content of muscle and backfat of heavy pigs. AB - The incorporation of fat in diets for heavy pigs may be necessary in order to increase their energy intake in the finishing period. Lard may be a good lipid source but it contains 10-13% of linoleic acid, which makes the subcutaneous fat less suitable for long term curing of raw ham. Partial hydrogenation of lard decreases linoleic acid content, but increases trans-fatty acid content. This trial involved two groups of pigs of 114kg live weight, fed for the last two months before slaughter with diets containing 3% lard (L) or 3% partially hydrogenated lard (PHL). The PHL contained about 10% trans-fatty acids and 2.5% linoleic acid. Rearing performance and carcass characteristics were unaffected by treatment. The group fed PHL showed a lower percentage of linoleic acid in the backfat (PHL 12.28% vs. L 13.04%) and a higher percentage of C18:1 trans-fatty acids both in backfat (0.5% vs. 0.06%) and in intramuscular fat (0.2% vs. 0.04%). PMID- 22061211 TI - Characterisation of a traditional Finnish liver sausage and different types of Spanish liver pates: A comparative study. AB - The physico-chemical characteristics of a traditional Finnish liver sausage (FLS) and different types of Spanish porcine liver pates (commercial, home-made and experimental) were studied. The characteristic recipes and different protocols of manufacture influenced the chemical composition and oxidative stability of the liver products. FLS showed, amongst the liver products, the smallest percentage of monounsaturated fatty acids (MUFAs) and the highest of polyunsaturated fatty acids (PUFAs) acids, including long-chain PUFAs. From a nutritional point of view, the FLS showed the smallest n-6/n-3 value whereas the experimental liver pate (ELP) presented the smallest ratio between hyper- (lauric, myristic and palmitic acids) and hypocholesterolemic fatty acids (oleic and linoleic acids). A large variety of volatile compounds were isolated from the liver products including lipid-derived volatiles, Strecker aldehydes and alcohols, sulphur and nitrogen containing compounds and volatile terpenes, providing information on their oxidative stability and aroma characteristics. The FLS presented a balanced profile between lipid-derived volatiles and volatile terpenes from spices. The presence of potent odorants from added flavourings in the commercial liver pate (CLP) could mask undesirable aroma odours from a large variety of lipid-derived volatiles. The home-made liver pate (HMLP) also presented large amounts of lipid derived volatiles as a likely consequence of strong thermal treatment during cooking, the presence of high amounts of iron and the absence of sodium nitrites and ascorbate in its composition. The ELP showed the simplest profile due to its high oxidative stability and the absence of added spices. PMID- 22061212 TI - Lipolysis in intramuscular lipids during processing of traditional Xuanwei ham. AB - Lipolysis in intramuscular lipids during the processing of Chinese Xuanwei ham has been studied by analyzing the changes of glycerides, phospholipids and free fatty acids in biceps femoris muscle. Results showed that the glycerides accounted for 73.2% of total lipid content in fresh ham, the phospholipids represented 25.3% and the free fatty acids 2.3% of the total lipid content, respectively. A rapid lipolysis of phospholipids occurred during the first 4 months of processing and slowed down during the rest period. A preferential hydrolysis for palmitic, linoleic and arachidonic acids in phospholipid fraction was observed. Glycerides only changed a little throughout the process, while an increase of free fatty acids during processing was observed. The results suggest that phospholipids are the main substrate of lipolysis in the intramuscular lipids of Chinese Xuanwei ham. PMID- 22061213 TI - Prevalence of Shiga toxin-producing Escherichia coli in beef. AB - Over the past two decades, many human illness outbreaks were attributed to consumption of undercooked beef products containing Shiga toxin-producing Escherichia coli (STEC). The illnesses included mild or bloody diarrhea, hemorrhagic colitis, and the life-threatening hemolytic uremic syndrome (HUS). Tracing these outbreaks to O157 and an increasing number of non-O157 STEC strains suggests that beef safety concerns will continue to rise and may negatively affect the beef industry. To effectively address these concerns, it is critical to evaluate the role of beef in STEC infections. In this review, published reports on beef contamination were evaluated to assess prevalence rates and health risks of STEC isolates. Global testing of beef showed wide ranges of prevalence rates of O157 (from 0.01% to 54.2%) and non-O157 (from 1.7% to 62.5%) STEC. Of the 155 STEC serotypes found in beef, 31 and 25 are known to cause HUS and/or other illnesses, respectively. PMID- 22061214 TI - Preslaughter handling of pigs and the effect on heart rate, meat quality, including tenderness, and sarcoplasmic reticulum Ca(2+) transport. AB - It is known that stress applied to pigs can be of influence on meat quality combined with disturbed regulation of the intracellular Ca(2+) concentration. However, the effect on meat tenderness is not sufficiently known. In an experiment with pigs two kinds of stress (immobilisation by a nose snare (nose) and the use of an electrical goad (goad)) for 5min just before slaughter were used and the results compared with minimum stress pigs (control). To quantify the level of stress, the heart rate during stress application was determined and it was found that the stress effect was highest in the goad pigs and surprisingly decreasing during the use of a nose snare. The meat quality did not differ between nose and control pigs, but was inferior in the goad group. Also, the goad stress significantly reduced the Ca(2+) transport of the sarcoplasmic reticulum. The principal hypothesis, that a disturbed Ca(2+) transport will affect the tenderness by activating the calpain system, could not be verified. Tenderness did not differ between experimental groups using 24 h post-mortem samples, neither was there a difference in tenderness after storing the meat samples for 6 days. PMID- 22061215 TI - Effect of modified atmospheres on microbiological, color and sensory properties of refrigerated pork. AB - Pork loin samples were stored (4 degrees C) in nylon polyethylene plastic bags using different modified atmospheres packaging (MAP): vacuum, 100% CO(2) 99% CO(2)+1% CO, 100% O(2) or 100% CO followed by vacuum. Throughout the storage period Pseudomonas growth was limited in loins packaged in all MAPs evaluated, except for 100% O(2). Psychrotrophs reached 10(7)CFUg(-1) after 20 days of storage except for the loin samples in 100% O(2) MAP that present count above 10(8)CFUg(-1). The 1%CO/99%CO(2) atmosphere was best for preserving the desirable pork loin color and the L* and a* values remained similar to the fresh meat values using this MAP. Pork loins in 99%CO(2)/1%CO MAP obtained the highest consumer acceptance scores after 24h of storage. These samples and those treated with CO and then vacuum packaged received the greatest acceptance scores even after 20 days of storage. PMID- 22061216 TI - Turkey breast meat functionality differences among turkeys selected for body weight and/or breast yield. AB - Functional meat characteristics were studied in three turkey lines, (1) RBC2: representing 1960s commercial turkeys, (2) F-line: a line selected for body weight (BW) and (3) C-line: a fast growing commercial line with enhanced breast muscle yield. The RBC2s Warner-Bratzler shear force values for the Pectoralis major (PM) were lower than the F- and C-lines' values (P<0.05). The WHC of the breast muscle from the C-line was lower compared with the RBC2 line (P<0.05), with the F-line being intermediate between, though not different from either the RBC2 or C-lines. A trend was observed, as the thermally induced meat gels from the RBC2 line PM had the highest storage modulus (G'), the F-line was intermediate and the C-line had the lowest storage modulus (P=0.09). These results suggest that selection for increased growth and breast muscle yield may be associated with decreased meat functionality in modern commercial turkeys. PMID- 22061217 TI - Performances and meat quality of two Italian pig breeds fed diets for commercial hybrids. AB - The effects of specific diets for commercial hybrids were investigated on 6 Casertana and 11 Mora Romagnola, two endangered Italian pig breeds. Average daily gain (ADG), feed conversion index (FCI), dressing percentage and meat and fat quality of animals bred under similar environmental and nutritional conditions were compared to define their optimal slaughtering weight. Animals were fed the same diets assuming that requirements of Mora Romagnola and Casertana did not differ, and changed every 30kg of weight gain. ADG and FCI were calculated every 15 days. Weight gains, divided into 5 groups based on live weight (LW) of animals (?60kg, 60160kg), showed higher values for Casertana than Mora Romagnola, particularly from 121 to 160kg LW (687g/d). Average FCI from 50 to 160kg LW was similar in both breeds (4.2). After 403 days of trial, animals were slaughtered at about 195kg LW. Carcass measurements showed that Casertana had higher dressing percentage and lean cuts than Mora Romagnola. Both breeds showed extraordinary high ultimate pH values of M. longissimus thoracis (5.96 and 6.15 for Casertana and Mora Romagnola, respectively) M. semimembranosus (6.37 and 6.30), showing an incomplete post mortem glycolysis. Colour of M. longissimus thoracis did not differ between breeds and was particularly dark. Chemical analysis of Casertana meat showed lower percentage of water and fat; the total amount of fatty acids (SFA, MUFA and PUFA) and the SFA/UFA ratio did not show significant differences between breeds. Results showed that from a growth point of view the optimal slaughtering weight of Casertana and Mora Romagnola should not exceed 160kg LW. Both breeds had an uncommon reactivity to stress probably due to interactions of genetic, nutritional and management factors. PMID- 22061218 TI - Changes in fatty acid composition and improved sensory quality of backfat and meat of pigs fed bacterial protein meal. AB - A total of 48 pigs (11.4 and 107.2 kg initial and final weight) were used to evaluate increasing dietary levels of bacterial protein meal (BPM) produced on natural gas (0, 50, 100, or 150 g kg(-1)) on fatty acid composition, sensory properties, and susceptibility of pork to lipid oxidation. Increasing levels of BPM to diets increased the content of C16:1 fatty acids in backfat and muscle and total monounsaturated fatty acids in muscle, but decreased the content of polyunsaturated fatty acids and iodine value in backfat and muscle. Pigs fed diets containing BPM had reduced thiobarbituric acid reactive substances (TBARS) value in backfat and muscle, reduced intensity of odor and rancid odor and taste in pork after short-time storage, and reduced off-odor and off-taste after intermediate-time storage. To conclude, adding BPM to diets for pigs changed the fatty acid profile, improved the oxidative stability, and sensory quality of pork. PMID- 22061219 TI - Serine peptidase inhibitors, the best predictor of beef ageing amongst a large set of quantitative variables. AB - For consumers, tenderness is the most important sensory attribute of beef meat and, though to a lesser extent, of pork. Tenderness is therefore by far the most common cause of its unacceptability. The major challenge for the beef industry is to evaluate the toughness of the meat as soon as possible after death. In this context, the aim of the present work was to develop an equation to predict the myofibrillar ultimate resistance of raw meat. The study was done on the Longissimus muscle from twenty three 19 months-old Charolais bulls grown in the same INRA farm. Muscles excised within 1h post-mortem were vacuum packed and stored at 15 degrees C during 24h and then transferred to 4 degrees C until used. The activities of lactate dehydrogenase, citrate synthase and myofibrillar Mg-Ca dependent ATPase, the levels of lactate dehydrogenase enzyme, myoglobin, myosin types I, IIa and IIb, cysteine and serine peptidase inhibitors, the pH, the osmolarity, the expressible juice, MU-calpain, m-calpain and calpastatin and meat toughness were measured. According to the physical method used here, the force measured on raw meat represents the resistance of the myofibillar structure. Stepwise linear regression was used to determine the best equation (p<0.05) for predicting toughness at 6 days post-mortem. A 6-variables predictive equation including serine peptidase inhibitors (partial R(2)=0.4), the rate (partial R(2)=0.25), and the extent of pH decline (partial R(2)=0.03), the at death LDH activity (partial R(2)=0.24), the extent of increase in osmotic pressure (partial R(2)=0.13), and the rate of MU-calpain activity loss (partial R(2)=0.09), explained 70% of the variability in meat toughness at 6 days post-mortem. This equation was developed from 20 animals and the other 3 animals, chosen randomly, were used to validate it. The absolute need for a predictive model of meat toughness and the nature of the serine peptidase inhibitors together with their potential target enzymes are discussed. PMID- 22061220 TI - Innovative wholesale carcass fabrication and retail cutting to optimize beef value. AB - Innovations in beef carcass fabrication to improve subprimal yield, retail cut yield, and overall carcass value were evaluated. Alternating sides from 30 beef carcasses were assigned to either an innovative or conventional style of fabrication. The innovative method resulted in greater (P<0.001) total subprimal yield and less (P<0.001) lean trimmings from the forequarter; however, hindquarter total subprimal yield and lean trimmings were not affected (P>0.05) by fabrication style. Value was greater for the innovative forequarter (P<0.001) and hindquarter (P<0.01), and total value was increased by more than US $14 per beef carcass compared to the conventional style. Selected subprimals were evaluated in retail cutting tests. In general, the innovative retail subprimals had yields equal to or greater than the conventional subprimals. Innovative carcass fabrication may allow for greater marketing options for beef cuts to improve carcass value and to offer greater retail merchandizing opportunities. PMID- 22061221 TI - Effects of starter cultures on the formation of flavour compounds in dry sausage. AB - The purpose of this work was to study the impact of starter cultures on the production of flavour compounds in dry sausages. The effect of six starter cultures corresponding to different combinations of lactic acid bacteria (Lactobacillus sake L110, Pediococcus acidilactici 725, P. pentosaceus 716) and different Staphylococcus species (S. carnosus 833, S. warneri 863, S. saprophyticus M31) strains were tested in a total of 30 dry sausages without spices. The analysis of flavour compounds using a dynamic headspace apparatus coupled to a gas chromatograph and a mass spectrometer enabled us to identify about 80 volatile compounds. They were of various origins-lipids oxidation, fermentations, amino acid catabolism and animal feedstuffs. The influence of the starters and especially the flavouring strains proved to have a major effect on the level of volatile compounds in dry sausages. The flavour tests led to more accurate determination of the sensory characteristics of important molecules in the flavour of dry sausages. The sensory analyses showed that the butter odour of dry sausages largely depends on the catabolism of carbohydrates and that curing and rancid odours were correlated with some typical compounds of lipid oxidation. PMID- 22061222 TI - Comparison of sensory characteristics and fatty acid composition between Wagyu crossbred and Angus steers. AB - Angus (n = 10) and crossbred (3 4 and 7 8 ) Wagyu (n = 10) steers were fed a diet according to typical Japanese standards for 552 days. The steers were fed to gain approximately 0.90 kg/head/day. Fatty acid composition was determined for subcutaneous and intramuscular adipose tissue, and M. longissimus dorsi muscle. Trained sensory evaluation and a consumer triangle test were performed on M. longissimus dorsi muscle steaks. For subcutaneous and intramuscular tissue. Wagyu adipose tissue possessed higher (P < 0.05) percentages of 14:1, 16:1 and 18:1 and a lower (P < 0.05) percentage of 16:0 and 18:0 than corresponding tissues from Angus steers. Trained sensory panel analysis revealed no differences (P < 0.05) in any of the sensory traits between steaks from Wagyu crossbred and Angus steers. However, a consumer triangle test indicated that consumers can detect a difference between breeds. PMID- 22061223 TI - Maximising the cost-efficiency of assay procedures. AB - Cortisol concentrations were measured in cattle plasma and pig muscle juice samples obtained from groups of animals slaughtered at different abattoirs. Statistically significant (P < 0.001) differences were obtained for between abattoir comparisons for both the cattle and pig samples. Cortisol concentrations were determined using a radio-immunoassay kit. In accordance with the instructions, assays were performed in duplicate. An analysis of variance indicated that the use of a single determination on more samples, instead of duplicate determinations of fewer samples, would have led to an important increase in accuracy for detecting differences between means. It would have been more cost-efficient to collect additional samples and perform one assay only on each sample. PMID- 22061224 TI - Frozen storage conditions and rancid flavour development in lamb. AB - Frozen storage of lamb at temperatures of -5 or -10 degrees C before ultimate storage at -35 degrees C induced changes that led to rancidity development (as assessed by a taste panel) continuing at a more rapid rate at the lower temperature. Parallel storage regimes, but with storage at -35 degrees C first, then ultimate storage at -5 degrees C or -10 degrees C, led to much less storage flavour development. No significant flavour changes occurred even after 40 weeks storage at -15 degrees C followed by 20 weeks storage at -35 degrees C. These studies emphasise the importance of order of time-temperature holding treatments in studies of rancid flavour development and indicate that time-temperature effects may not be truly additive. PMID- 22061225 TI - Effect of the RN(-) gene on ultrastructure and protein fractions in pig muscle. AB - The aim of the present experiment was to study the effect of the RN(-) gene on ultrastructure of white fibres and the proportion of the different protein fractions in Longissimus lumborum muscle of RN(-) pigs. The ultrastructure of muscle was observed in 4 RN(-) carrier pigs and 4 rn(+)rn(+) homozygous pigs by mean of electron microscopy. Protein fractionation and quantification were performed on muscle from a second group of 4 RN(-) and 4 rn(+) pigs. No change in the proportions of the different protein compartments was observed. The abnormality of the glycolytic fibres of RN(-) pigs seems to be rather due to an increase of the glucid concentration in the sarcoplasm, perhaps secondarily to a modified osmolarity in the intracellular medium. PMID- 22061226 TI - Potential role of Proteus-Providencia-Morganella species in quality deterioration of beef. AB - Proteeae Isolation Medium of Hawkey et al. (1986) was effective for isolation and enumeration of Proteus-Providencia-Morganella spp. from beef and beef products. On this medium colonies were brown, surrounded by a zone of clearing. In an examination of retail beef samples packaged and stored in polyvinyl chloride (PVC) film, 5% contained these bacteria in a concentration of 10(1)-10(2) cells per gram or cm(2). Isolates from retail beef samples included P. vulgaris, P. alcalifaciens, P. rettgeri, and M. morganii. None of the retail samples packaged and stored in high oxygen barrier (HOB) film contained detectable Proteus Providencia-Morganella spp. Steaks inoculated with Proteus-Providencia-Morganella spp. and packaged and stored at 4 degrees C in PVC film (15 days) or in HOB film (42 days) usually had a reduced count of Proteus-Providencia-Morganella spp. during storage. Slight increases in counts occurred on steaks inculated with P. vulgaris and P. rettgeri and stored at 4 degrees C for 15 days in PVC film. PMID- 22061227 TI - Effect of freezing, thawing and frozen storage on physico-chemical and sensory characteristics of buffalo meat. AB - A study was conducted on some physico-chemical and sensory characteristics of buffalo meat frozen by plate and blast freezing and stored at -15 +/- 3 degrees C for a period of 3 months. A marginal increase in pH values and drip losses were observed during the storage period. Drip losses were less in blast frozen samples. WHC, cooking losses thermal shrinkage and WB Shear values indicated inconsistent results, during storage. Similar observations were recorded with regard to tyrosine and TBA values. No significant differences in the physico chemical characteristics were observed between meat cuts and minced meat. Plate frozen meat samples scored higher for texture, juiciness and aroma. Both the plate and blast frozen meat samples, however, were similar in overall quality according to taste panel results. PMID- 22061228 TI - Effects of porcine somatotropin (PST) administration on the fat/lean content and processing properties of pork bellies. AB - Porcine somatotropin (PST)-supplemented pigs were slaughtered at 109 or 131.8 kg; bellies were analyzed for compositional and bacon processing characteristics and compared with bellies from controls (slaughtered at 109 kg). Bellies from control and 109 kg, PST-treated pigs were significantly lighter (P < 0.01) in weight whereas the PST-treated bellies were significantly (P < 0.01) leaner than controls regardless of slaughter weight. The leaner bellies resulted in greater (P < 0.01) brine pickup, reduced smokehouse yields and bacon with less fat regardless of slaughter weight. Frying yield for the bacon from PST-treated pigs was significantly (P < 0.01) higher than that of the controls probably because of the fat/lean difference. The changes observed in bacon from PST-supplemented pigs appear to be due to the compositional change induced by PST administration. PMID- 22061229 TI - Effect of antioxidants on the sensory characteristics and storage stability of aseptically processed low-fat beef gels. AB - Beef gels, formed by heating, targeted to contain 13% protein and 16% fat and subjected to one of four antioxidant treatments, including no antioxidant, rosemary oleoresin, sodium nitrite, or sodium nitrite and rosemary oleoresin combined, were produced, aseptically processed (AP), packaged in a sterile container and stored at 3 degrees C. The day after aseptic processing, the four AP gels and a no-antioxidant, unprocessed gel were evaluated by a trained sensory panel for textural and flavor characteristics. On days 1, 14, 29 and 42 after processing, the AP gels were evaluated for shear stress and shear strain using torsion fracture analysis, and for oxidative stability using headspace gas chromatography. Sensory results indicated significant (P < 0.10) differences in hardness, juiciness and metallic flavor between the AP and unprocessed plain gels. Among the AP gels, the panel identified differences in oxidized flavor and beef flavor due to antioxidant treatment. Differences in shear stress were found due to aseptic processing and in shear strain due to storage time. Differences in the concentrations of total aldehydes, hydrocarbons and alcohols were found due to storage time (increased with time) and antioxidant treatment (decreased with antioxidant addition). Total ketones varied due to time only and total nonheterocyclic sulfur compounds varied due to antioxidant treatment only. The use of antioxidants appears to improve the sensory characteristics and oxidative stability of AP beef gels. PMID- 22061230 TI - Lipolytic and microbial changes during the natural fermentation and ripening of Greek dry sausages. AB - The hydrolytic changes in the lipid fraction and the changes in microbial growth during the natural fermentation and ripening of Greek dry sausages were studied. Two batches were manufactured under industrial conditions, without the addition of starter cultures. The results of the microbiological analyses indicated that, among the micro-organisms well known for their lipolytic activity, micrococci were predominant during the whole fermentation-ripening process. It was shown that the fatty acid composition of the hydrolysed lipid fraction did not remain constant with time. Analysis of the experimental results indicated that, given the length of the aliphatic chain (16 or 18 carbon atoms), the more unsaturated fatty acids were hydrolysed in preference to the saturated homologues. On the other hand, fatty acids having 16 carbon atoms were hydrolysed in preference to the iso-unsaturated ones having 18 carbon atoms. PMID- 22061231 TI - Contaminant lactic acid bacteria of dry sausages produce histamine and tyramine. AB - Exogenous biogenic amines present a food poisoning hazard in fermented foods especially with additional risk factors, e.g. amine oxidase inhibiting drugs, alcohol and gastrointestinal diseases. Forty-two lactic acid bacteria (LAB) strains were isolated from seven dry sausages during ripening (0 day, 21 day and 49 day). Their ability to produce histamine and tyramine was studied by HPLC detection from broth cultures after 2 days incubation. The tyramine and histamine concentrations in sausages increased during fermentation. 10 of 42 LAB strains produced 402-1087 ppm tyramine. Four of these 10 contaminant LABs were also histamine-positive (725-1083 ppm). Most of the amine positive strains were found in sausages at the end of ripening and with highest amine levels. On the basis of these results the contaminant LABs play an important role in tyramine and histamine formation during the ripening of dry sausages. Therefore it could be possible to decrease the levels of amines formed by limiting the initial level and growth of these contaminant bacteria. PMID- 22061232 TI - Hot water decontamination of beef carcasses for reduction of initial bacterial numbers. AB - Areas on freshly slaughtered beef carcasses were sprayed with hot (95 degrees C), sterilized, distilled water in order to elevate carcass surface temperature to 82 degrees C. A significant (P < 0.05) reduction in bacterial numbers was observed between control (prespray) and hot water treated carcass surfaces. These results indicate that microbial decontamination of beef carcasses with hot water will be effective if an approprite spraying apparatus is used. PMID- 22061233 TI - Listeria monocytogenes: Occurrence in beef and identification of the main contamination points in processing plants. AB - This study aimed to establish the occurrence of Listeria spp., especially L. monocytogenes and its main serotypes, in beef and processing plants. A total of 443 samples were obtained from equipment, installations and products from 11 meat processing establishments from Parana state, Brazil. All samples were analyzed using USDA methodology for Listeria spp. detection, followed by species identification. The occurrence of Listeria spp. in the samples was 38.1% of which 51.4% were from equipment, 35.4% from installations and 30.2% from products. The identified species were: L. monocytogenes (12.6%), L. innocua (78.4%), L. seeligeri (1.2%), L. welshimeri (7.2%) and L. grayi (0.6%). The identified serotypes of L. monocytogenes were 1/2a and 4b. The results demonstrate the significance of equipment and installations as sources of contamination by Listeria spp. and L. monocytogenes in the processing of beef and meat products. PMID- 22061234 TI - Performance of Cinta Senese pigs and their crosses with Large White 2. Physical, chemical and technological traits of Tuscan dry-cured ham. AB - Technological, chemical and physical traits of cured ham from Cinta Senese and Large White pigs, and their crosses were investigated. Hams were obtained from 29 Cinta Senese (CS), 29 Large White*Cinta Senese (LW*CS) and 12 Large White (LW) pigs, fed a commercial mixture. Sensory and chemical-physical analysis was performed on a sample-slice and on muscles (Biceps femoris - BF; Semimembranosus SM; Semitendinosus - ST) and subcutaneous fat. CS showed the highest trimming loss and the lowest salting loss. Hams of CS pigs scored higher for fatness than those of LW pigs, LW*CS showing intermediate values. On sample-slice, CS exhibited higher firmness, redness and marbling of lean, and greater fat extension than LW, with crosses having intermediate scores. Muscle moisture was lowest in CS, while both SM and BF from LW had the highest percentage of protein and the lowest of ash. CS showed higher intramuscular fat content than LW*CS and LW. Shear force of BF was higher in CS than in LW*CS and LW. With respect to LW, CS had lower values of L(*) in muscles, and higher values of a(*) in subcutaneous fat. Subcutaneous fat of CS contained less SFA and more MUFA than LW*CS and LW. PMID- 22061235 TI - Evaluation of the antioxidant potential of grape seed and bearberry extracts in raw and cooked pork. AB - The effect of grape seed extract (GSE) and bearberry (BB), on lipid oxidation (TBARS, mg malondialdehyde (MDA)/kg muscle), colour (CIE 'a' redness value), pH, microbial status (log(10)CFU colony forming units/g pork) and sensorial properties of cooked pork patties was investigated. GSE (0-1000MUg/g muscle) and BB (0-1000MUg/g muscle) were added to raw pork (M. longissimus dorsi) patties which were stored in modified atmosphere packs (MAP) (75% O(2):25% CO(2)) for up to 12 days at 4 degrees C. Cooked pork patties were stored in MAP (70% N(2):30% CO(2)) for up to 4 days at 4 degrees C. Mesophilic plate counts and pork pH were unaffected by GSE and BB. GSE and BB addition decreased (P<0.05) lipid oxidation (TBARS) in raw pork patties on days 9 and 12 of storage, relative to controls. Antioxidant activity of GSE and BB was observed in cooked pork patties demonstrating the thermal stability of GSE and BB. The 'a' redness values of raw and cooked pork patties marginally increased with increasing GSE concentration. The sensory properties of cooked pork patties were unaffected by GSE and BB addition. Results obtained demonstrate the potential for using health promoting nutraceuticals in meat and meat products. PMID- 22061236 TI - High intensity ultrasound effects on meat brining. AB - Pork loin (longissimus dorsi) samples of two different geometries, cylinders and slabs, were immersed in saturated NaCl brine for 45min under different conditions: without brine agitation (STAT), with brine agitation (AG) and with ultrasound application (US) at eight levels of ultrasonic intensity. Moisture content change and NaCl gain were considered in order to evaluate the difference in the brining treatments. No significant differences were found in moisture and NaCl content of samples treated under STAT conditions and AG conditions, while the influence of ultrasound on the mass transfer process during meat brining depended on the intensity applied. There was an ultrasonic intensity threshold above which the influence of ultrasound appeared. At the highest level of intensity studied, the water content of samples was significantly higher than the initial water content of meat. As regards NaCl transfer, once above the intensity threshold, the increase in the NaCl content was proportional to the applied ultrasonic intensity. Not statistically significant differences were found for sample geometry. PMID- 22061237 TI - A new region-primitive method for classification of colour meat image texture based on size, orientation, and contrast. AB - A new structural method was developed to characterise texture of colour meat images. Structural primitives or region-primitives were constructed using a region-growing method with a global and automatically calculated threshold. A total of eight textural features under the consideration of size, orientation, and contrast, which are the primary factors of human perception of texture pattern, were obtained from the region-primitives. An experiment was set up to classify the texture pattern of a set of 60 cooked meat colour images consisting of 20 beef images, 20 lamb images, and 20 pork images using texture features obtained from the proposed region-primitive method and run-length matrix method, respectively. The proposed region-primitive method (error rate: 18.3%) was found to perform better than the run-length matrix method (error rate: 35.0%). Results also indicated that the texture features obtained by the proposed method carried adequate texture information for classification and that the proposed region primitive method could be potentially used for the characterisation of irregular textural pattern in cooked meat images, which was inapproachable by conventional structural texture analysis techniques. PMID- 22061238 TI - Quantitative determination of saturated-, monounsaturated- and polyunsaturated fatty acids in pork adipose tissue with non-destructive Raman spectroscopy. AB - The composition of dietary fat has received increased attention during the recent years because it influences human health. Seventy seven samples from pork adipose tissue and melted fat from the same tissue were measured with Raman spectroscopy. Gas chromatography analysis was conducted as reference. Iodine values (IV) ranged from 58.2 to 90.4g iodine added per 100g fat. Polyunsaturated fatty acids (PUFA) ranged from 7.8% to 31.7% and monounsaturated fatty acids (MUFA) from 35.2% to 51.5% of total fatty acids. When applied on pre-processed spectra of melted fat, partial least square regression (PLSR) with cross-validation gave a correlation coefficient (R)=0.98, and root mean square error of cross-validation (RMSECV)=1.4 for IV, using 3 PLS factors in the model. PUFA gave R=0.98 and RMSECV=1.0% of total fatty acids, using 5 PLS factors. MUFA were predicted with R=0.96 and RMSECV=1.0% of total fatty acids, using 9 PLS factors. On adipose tissue a model with 3 PLS factors gave R=0.97 and RMSECV=1.8 for IV. For PUFA, a model with 3 PLS factors gave R=0.95 and RMSECV=1.5% of total fatty acids. For MUFA a model with 6 PLS factors gave R=0.91 and RMSECV=1.5% of total fatty acids. The results indicate the feasibility to use Raman spectroscopy as a rapid and non-destructive method to determine IV, PUFA, MUFA and saturated fatty acids (SFA) measured directly on pork adipose tissue and in melted fat from the same tissue. PMID- 22061239 TI - Consequences of two or four months of finishing feeding of culled dry dairy cows on carcass characteristics and technological and sensory meat quality. AB - Finishing feeding was evaluated as a way to improve carcass-, meat- and eating quality of culled dairy cows. In total, 125 Danish Friesian cows were purchased from commercial dairy herds. Cows were culled for various typical reasons at different stages of lactation, were non-pregnant and had milk yield at culling ranging from 1 to 25kg/d and had LW varying from 330 to 778kg. Cows were housed in tie-stalls and had free access to barley straw and water during a 7-d drying off period. Cows were allocated to three equal treatment groups based on parity, LW, BCS, and culling reason. A control group (C) was slaughtered immediately after drying-off (n=43), a group (F2) was finishing-fed for 63 days (n=41), and a group (F4) was finishing-fed for 126 days (n=41). In the finishing period, cows had free access to a TMR (10.6 MJ ME and 130g CP per kg of DM). Cows on treatment, F2 and F4 gained 1.16+/-0.05kg/d in the finishing period. Compared with C-cows, F2- and F4-cows had 56 and 97kg higher carcass weight, 10% and 21% larger Longissimus muscle area, and 14 and 70% more backfat, respectively, at time of slaughter. EUROP conformation scores were 2.2 (C), 3.4 (F2) and 4.4 (F4) and EUROP fat scores were 1.9, 3.0 and 3.7. Finishing feeding increased IMF, improved meat flavour and colour, and tended to reduce shear force value and improve tenderness and juiciness. The F4 cows also had higher fat trim than C- and F2-cows. Cows were divided into two parity groups (1st parity and older cows). Compared with 1st parity cows, older cows ate 12% more feed, had similar daily gain, were heavier, and had higher BCS and fatness including IMF. The results show that it is possible to dry-off and finish-feed culled dairy cows resulting in larger muscles, increased fatness, improved overall carcass quality and better technological as well as sensory quality characteristics. PMID- 22061240 TI - PCR identification of meats from chamois (Rupicapra rupicapra), pyrenean ibex (Capra pyrenaica), and mouflon (Ovis ammon) targeting specific sequences from the mitochondrial D-loop region. AB - A polymerase chain reaction (PCR) assay was developed for the identification of meats from chamois (Rupicapra rupicapra), pyrenean ibex (Capra pyrenaica), and mouflon (Ovis ammon) by using oligonucleotides targeting mitochondrial D-loop sequences. A D-loop region (~700-1000 bp) was firstly amplified and sequenced from various game and domestic meat DNAs, and three primer sets were then designed on the basis of nucleotide multialignment of the generated D-loop sequences. As expected from sequence analysis, PCR amplification of the targeted D-loop fragments was successfully achieved from chamois (88 bp), pyrenean ibex (178 bp), and mouflon (155 bp) meats, showing adequate specificity and reproducibility against a number of game and domestic meats. Mouflon and sheep meats were amplified together in accordance to the high nucleotide identity of their mt D-loop sequences. In this work, satisfactory amplification was also accomplished in the analysis of experimentally pasteurized (72 degrees C for 30min) and sterilized (121 degrees C for 20min) meats, with a detection limit of ~0.1% for each of the targeted species. The proposed PCR assay represents a rapid and straightforward method for the detection of possible adulterations in game meat products. PMID- 22061241 TI - Mould growth on traditional greek sausages and penicillin production by Penicillium isolates. AB - Visible moulds were isolated and identified from traditional Greek sausages from Northern Greece. Penicillium species were isolated from 90.8% of visibly mouldy sausages. Penicillium solitum, P. nalgiovense and P. commune species made up 60.6% of the total number of isolates. The most frequently occurring species was P. solitum (26.1%). P. nalgiovense and P. olsonii were found to be positive to penicillin production in an agar assay and further examination for antibiotic production in liquid culture with complex media designed for penicillin production, confirmed their ability for penicillin biosynthesis. Penicillin production by P. olsonii is reported for the first time in this study. PMID- 22061242 TI - Single nucleotide polymorphism in growth hormone gene exon-4 and exon-5 using PCR SSCP in Black Bengal goats - A prolific meat breed of India. AB - Single-strand conformation polymorphism (SSCP) showed 7 and 5 haplotypes in caprine GH gene exon-4 and exon-5 in Black Bengal, a prolific meat breed from India. All haplotypes revealed novel sequences. In exon-4 codons 6, 36 and 54 were polymorphic. At codon 6, AA arginine (R) changed to histidine (H) and proline (P), showing 6RR, 6HH and 6PP genotypes. At codons 36 three genotypes DD, VV and DV were observed due to SNP showing changed from aspartic acid (D) to valine (V). At codon 54, AA change from arginine to tryptophan (W) and 54RR and 54WW genotypes were observed. SNPs were also observed at codon 23 (serine to threonine) and at 37 (arginine to proline) in 8% of goats. In exon-5 nucleotide substitution (G/A) at codon 10 and (A/G) at 14 respectively changed AA from glycine (K) to glutamic acid (E). Silent mutations were also observed. PMID- 22061243 TI - Species identification and authentication of tissues of animal origin using mitochondrial and nuclear markers. AB - We evaluated and compared the utility of mitochondrial markers viz. 16S rDNA and NADH dehydrogenase subunit 4 (ND4) and a nuclear marker viz. the actin gene to identify the specimens of animal origin for forensic identification, food regulatory control and to prevent illegal trading, poaching and conservation of endangered species. We also tested PCR fingerprinting methods like RAPD and actin barcoding to generate species-specific "fingerprints". Our results suggested that mitochondrial markers are more efficient than nuclear markers for the purpose of species identification and authentication. Among PCR fingerprinting approaches, RAPD was proved to be more discriminatory, accurate and efficient than actin fingerprinting. Considering the present scenario in trading of vertebrate animal tissues like buffalo, cow, pig, goat, chicken, frogs, fishes and snakes etc., mitogenomics based technology proved to be efficient and reliable in resolving problems like meat adulteration and smuggling across countries. PMID- 22061244 TI - Effect of different stunning systems on meat quality of light lamb. AB - The present study was proposed to compare the effect that different types of stunning (TS) had on the quality of refrigerated meat from light lambs of the Spanish Manchega breed at 24h and 7 days post-mortem. Lambs were electrically stunned (ESL; n=10), using CO(2) (GSL; n=10) or slaughtered without previous stunning (USL; n=10). Measurements on meat quality were carried out by evaluating pH, colour coordinates (L(*), a(*), b(*)), water holding capacity (WHC), cooking loss (CL), shear force (SF) and drip loss (DL). At 24h post-mortem, no significant differences were found in any of the variables studied. However, at 7 days post-mortem, meat quality was affected by the different TS: pH, CL and DL were lower (P<0.001) in the USL group and GSL obtained the lowest a(*) (redness) and b(*) (yellowness) values (P<0.01) than in the other groups. Ageing of meat affected SF in the ESL group (P<0.01), although there were no significant differences due to treatments at any of the ageing times. PMID- 22061245 TI - Characterisation of intramuscular, intermuscular and subcutaneous adipose tissues in yearling bulls of different genetic groups. AB - Fatty acid (FA) composition of intramuscular (IM, Longissimus thoracis muscle), intermuscular (IT) and subcutaneous (SC) fat of one hundred intensively fed yearling bulls with different propensities to fatten were studied. Meat samples were collected from Asturiana de los Valles bulls with different genotypes with respect to the myostatin gene (mh/mh n=24, mh/+ n=26 and +/+ n=25) and from Asturiana de la Montana (n=25) bulls lacking the mutation responsible for double muscling and characterised by small to medium-frame size adapted to less favoured mountain areas. FA profiles were expressed as percentages of total FA (g/100g of total FA) and organised into groups (saturated (SFA), branched (BFA), monounsaturated (MUFA), C18:1trans, polyunsaturated (PUFA), n-6, n-3, conjugated linoleic acids (CLA), unsaturated (UFA)) and ratios (MUFA/SFA (M/S), PUFA/SFA (P/S), UFA/SFA (U/S), n-6/n-3). The IT depot was the most saturated and SC depot contained the most monounsaturated FAs, while IM fat had the most polyunsaturated FAs. IM fat showed the highest P/S ratio and for the n-6/n-3 ratio there were no significant differences between adipose tissue depots. In general, genotype effects were more pronounced in IM and SC fat profiles compared to the IT depot, for which no significant differences between genotypes were found in SFA, PUFA (including n-6 and n-3), UFA and most of the ratios. IM fat of mh/mh animals had the highest content of PUFA and thus the highest P/S ratio. Accordingly, the presence of the gene causing double muscling influenced the tendency to deposit carcass fat and its FA composition, mainly in IM fat. In general, when carcass fat decreased, SFA content decreased while PUFA and UFA contents increased due to the changes in their percentages. PMID- 22061246 TI - Modeling transfer of Escherichia coli O157:H7 and Staphylococcus aureus during slicing of a cooked meat product. AB - Cross contamination is one of the most important contributing factors in foodborne illnesses originating in household environments. The objective of this research was to determine the transfer coefficients between a contaminated domestic slicing machine and a cooked meat product, during slicing. The microorganisms tested were Staphylococcus aureus (Gram positive) and Escherichia coli O157:H7 (Gram negative). The results showed that both microorganisms were able to transfer to all slices examined (20 successively sliced) and at different inoculum levels on the blade (10(8), 10(6) and 10(4)cfu/blade). The results also showed that the number of log cfu transferred per slice, during slicing, decreased logarithmically for both microorganisms at inoculum levels of 8 and 6log cfu/blade. The type of microorganism significantly influenced transfer coefficients (p<0.05) and there was an interaction between inoculum level and transfer coefficient for S. aureus (p<0.05), but not E. coli O157:H7. Finally, to describe bacterial transfer during slicing, two models (log-linear and Weibull) were fitted to concentration on slice data for both microorganisms (at 6 and 8 log cfu/blade), obtaining a good fit to data (R(2)?0.73). PMID- 22061247 TI - Pre-selection of potential molecular markers for the geographic origin of dried beef by HR-MAS NMR spectroscopy. AB - The complexity of meat composition and the requirement of high analytical rates to prevent frauds and, in general, to assess food quality are stimuli to find analytical methods able to detect appropriate indicators of a given quality. We present here an evaluation of 1D (1)H HR-MAS NMR spectroscopy for the selection of potential molecular markers of one specific quality, geographic origin. Dried beef samples of certified origin were tested, and preliminary results on a limited sample set confirmed the good aptitude of this method for rapid food analysis, demonstrated earlier on dairy products. Fat content as well as specific metabolites, probably linked to feeding system, are shown to be good candidates for markers of origin. These results are in agreement with recent studies on the relative impact of genetic and dietary conditions on the metabolic profile of animal specimens. (1)H HR-MAS is thus an interesting tool for pre-screening potential markers, that can complement standard chemical and biochemical analysis. PMID- 22061248 TI - Sheep carcass composition estimated from Longissimus thoracis et lumborum muscle volume measured by in vivo real-time ultrasonography. AB - The use of Longissimus thoracis et lumborum muscle (LM) volume measured in vivo by real-time ultrasonography (RTU) to estimate carcass composition was evaluated in 47 female sheep. Animals were scanned over six sites (7th, 9th, 11th and 13th thoracic vertebrae and 2nd and 4th lumbar vertebrae). After slaughter carcass weight (CW) and composition by dissection were determined. RTU volume measurements were calculated by multiplying the LM area at each site by the vertebra lengths. Equivalent measurements to those taken in vivo were obtained on the carcass using a digital camera and image analysis. The correlation between LM volume measured by RTU and in the carcass was high for all scans. LM volume was better in predicting carcass muscle than carcass fat. Lower determination coefficients were obtained between LM volume and carcass tissues expressed in % of CW. The best estimates of carcass tissues weights and proportions were obtained using the LM volume between the 2nd and the 4th lumbar vertebrae for all tissues. Multiple regression equations were fitted using live weight (LW) and LM volume to predict carcass composition. For all tissues, the best fit was obtained with two, three or four independent variables and the stepwise procedure was consistent in selecting LW to establish the prediction equations. Weights and proportions of muscle, subcutaneous fat, intermuscular fat and total fat were accurately predicted. These results indicate that Longissimus thoracis et lumborum muscle volume measured in vivo by RTU can be used to predict sheep carcass composition (muscle and fat). PMID- 22061249 TI - Lipid oxidation in lamb meat: Effect of the weight, handling previous slaughter and modified atmospheres. AB - This study examined the effect of pre-slaughter handling (electrical, gas (CO(2)) or non-stunning) on lipid oxidation (as thiobarbituric acid reactive substances, TBARS; in the unit of mg malondialdehyde/kg(-1) of meat) of Spanish Manchega breed lamb meat, at 24h and at 7 days post-mortem. Lambs were slaughtered at two different weights (light (L), 25kg, vs. suckling (S), 12.8kg). In general gas stunned lambs had lower lipid oxidation (P<0.001), and it was higher (P<0.001) in light lambs compared to suckling lambs. In both groups (S and L), malondialdehyde level increased with time (P<0.001), although this increase was lower (P<0.05) in gas-stunned suckling lambs. In addition, we evaluated the effect of stunning methods (TS: electrical vs. gas) and the weight (L vs. S) on lipid oxidation values in samples packed in different types of modified atmosphere (MA: A: 70%O(2)+30%CO(2); B: 69.3%N(2)+30%CO(2)+0.7%CO; C: 60%N(2)+40%CO(2)) at 7, 14 and 21 days post-packing. Values were higher in samples with MA-type A and lower in B and C types (P<0.05). A significant interaction (P<0.001) weight*TS was observed and the lowest rates of TBARS were found in the samples of light lambs stunned with gas and packed under anaerobic conditions (MA-B and C). PMID- 22061250 TI - Mitochondrial markers for the detection of four duck species and the specific identification of Muscovy duck in meat mixtures using the polymerase chain reaction. AB - A polymerase chain reaction (PCR) assay for the qualitative detection of four duck species in meat mixtures, and a second PCR assay for the specific identification of Muscovy duck, have been developed based on oligonucleotide primers targeting the 12S rRNA mitochondrial gene. The specificity of both assays was tested against a wide range of animal species. The technique was applied to raw and sterilized muscular binary mixtures, with a detection limit that ranged from 0.1% to 1.0% (w/w). The short length (less than 100bp) of the DNA fragments amplified with these primer pairs was found to be essential for the successful amplification in samples with highly degraded DNA, and consequently, it could be very useful in inspection programmes to enforce labelling regulation of heat and pressure-processed products, for which other methods cannot be applied. PMID- 22061251 TI - Moisture transport during cooking of meat: An analysis based on Flory-Rehner theory. AB - It is proposed that the moisture transport during cooking of meat can be described by the Flory-Rehner theory of rubber-elasticity. This theory contains the essential physics to describe the transport of liquid moisture due to denaturation and shrinkage of the heated protein matrix. The validity of the proposition is shown by a numerical model, which comprises a linearisation of the Flory-Rehner theory augmented with Darcy's law for porous media flow. The model is used to simulate cooking experiments performed with a rectangular piece of beef. Reasonable comparison between simulations and experiments is obtained. Further analysis of simulations renders insight of yet unexplained phenomena observed during cooking of meat. PMID- 22061252 TI - Intramuscular fatty acid composition of lambs given a tanniniferous diet with or without polyethylene glycol supplementation. AB - The aim of this trial was to investigate the effects that dietary tannins have on lamb intramuscular fatty acids. Twenty-seven lambs were divided into three homogeneous groups: control group, receiving commercial concentrate based on maize; tannin group, fed a diet based on carob pulp (45% as fed basis); PEG group, receiving the same diet as the latter with addition of 42g/kg of polyethylene glycol (PEG, a binding agent that eliminates the effects of condensed tannins). The duration of the trial was 45 d. Intramuscular fatty acids were measured in the longissimus dorsi muscle. The isomer cis-9 trans-11 of linoleic acid (conjugated linoleic acid or CLA) and linolenic acid were higher in the longissimus muscle fat from animals fed the control diet compared to the other groups (P<0.0005); these fatty acids were higher in the fat from animals fed the carob diet supplemented with PEG compared to those fed the same diet without PEG (P<0.05). trans-Vaccenic acid (C18:1 trans-11) was found at higher concentration in fat from control and PEG lambs compared to tannin lambs (P<0.01); the CLA/C18:1 trans-11 ratio was lower in lambs fed control and PEG diets than in tannin-fed animals (P<0.05). PMID- 22061253 TI - Fatty acids and tocopherol levels in M. Longissimus dorsi of beef cattle in Sweden - A comparison between seasonal diets. AB - This study investigated the influence of Swedish outdoor feeding systems on the fatty acid composition and tocopherol content of M. Longissimus dorsi from beef. Dietary effects of pasture (PA), silage, and silage supplemented with grain (SIG) were compared. Each dietary group consisted of six animals. Higher levels (P<0.05) of polyunsaturated fatty acids (PUFA) were found in the PA treatment. The n-6/n-3 fatty acid ratio of total lipids in the muscle tissue was in the range 1.2-1.5. The SIG treatment increased the n-6/n-3 ratio and decreased the total PUFA content of muscle tissue. The lipid class composition and the content of alpha-tocopherol in the meat showed no differences among treatments. PMID- 22061254 TI - Meat quality characteristics of springbok (Antidorcas marsupialis). 1: Physical meat attributes as influenced by age, gender and production region. AB - Springbok is the most extensively cropped game species in South Africa. The effects of age (adult, sub-adult, lamb), gender and production region on the physical attributes (pH(24), cooking and drip loss, Warner Bratzler shear force and colour) were determined using samples of the M. longissimus dorsi (LD) muscles of 166 springbok. Stressed animals had a higher (P<0.05) pH(24) (6.3+/ 0.07), as observed in the meat originating from the Caledon region. This meat had lower (P<0.05) cooking loss (27.2+/-0.62%) and drip loss (1.8+/-0.08%) values in comparison to meat originating from the other regions. Inverse correlations were noted between pH(24) and drip loss (r=-0.26, P<0.01) and cooking loss (r=-0.42, P<0.001). Shear force values (kg/1.27cm diameter) correlated positively (r=0.25, P<0.01) with pH(24). Age-related effects on tenderness were small in comparison with pH(24) effects. CIELab colorimetric values were typical of game meat and venison (L(*)<40, high a(*) and low b(*) values). It was noted that pH(24) correlated negatively (r=-0.51, P<0.001) and positively (r=0.33, P<0.001) with the hue-angle and the chroma value of colour, respectively. Springbok originating from Caledon had a significantly (P<0.05) higher a(*) value, indicating meat to be more red with higher colour saturation. PMID- 22061255 TI - Meat quality characteristics of springbok (Antidorcas marsupialis). 2: Chemical composition of springbok meat as influenced by age, gender and production region. AB - The effects of age, gender and production region on the chemical, mineral and amino acid composition of the M. longissimus dorsi (LD) muscle of springbok were investigated. There was a significant gender(*)region interaction for protein content - for the four production regions it varied between 18.80 and 21.16g/100g. The intramuscular fat (IMF) content of the LD muscle varied between 1.32 and 3.46g/100g. Females (3.13+/-0.28g/100g) had a higher (P<0.05) fat content than males (1.35+/-0.08g/100g). The IMF content of the adult (2.45+/ 0.26g/100g) and sub-adult (2.50+/-0.28g/100g) categories was higher (P<0.05) in comparison to that of the lambs (1.32+/-0.11g/100g). An inverse correlation was noted between the IMF and moisture content (r=-0.49, P<0.001) of the meat. The two main amino acids were glutamic and aspartic acid, which contributed 2.47-2.74 and 2.31-2.54g/100g of dry matter, respectively. Phosphorous was the predominant mineral in the LD muscle (122.92-159.78mg/100g of dry matter), followed by potassium (119.44-131.25mg/100g of dry matter) and calcium (6.57-145.18mg/100g of dry matter). Production region had a significant effect on the mineral and amino acid composition of the meat, while the effects of age and gender were found to be insignificant. PMID- 22061256 TI - Meat quality characteristics of springbok (Antidorcas marsupialis). 3: Fatty acid composition as influenced by age, gender and production region. AB - The effects of age, gender and production region on the fatty acid composition of springbok Musculus longissimus dorsi (LD) were investigated. The major fatty acid of the LD muscle was stearic acid (C18:0), which contributed 23.92-27.02%. Oleic acid (C18:1) represented the largest component (16.33-20.45%) of the mono unsaturated fatty acids (MUFA). The major n-6 polyunsaturated fatty acid (PUFA) was C18:2n-6, which formed 18.77-21.62%, whereas C18:3n-3 (3.33-4.00%) was the most abundant n-3 PUFA. The n-6:n-3 ratio of the meat varied from 3.02 to 3.35, with an average ratio of 3.2. Polyunsaturated to saturated (P:S) ratios varied between 0.96 and 1.18 and averaged at 1.06. Total MUFA was found to be higher (P<0.05) in males (20.99%) than females (16.67%). The cholesterol content of the meat varied from 54.45 to 59.34mg/100g muscle. Linear correlations between the fatty acid and the intramuscular fat (IMF) content indicated a significant increase in certain saturated and mono-unsaturated fatty acids with increasing IMF content of the meat. PMID- 22061257 TI - Meat quality characteristics of springbok (Antidorcas marsupialis). 4: Sensory meat evaluation as influenced by age, gender and production region. AB - The effects of age, gender and production region on the sensory characteristics of springbok M. longissimus dorsi (LD) were investigated in 19 springbok, which originated from two Nature Reserves in the Free State Province of South Africa and were divided into age (adult, sub-adult) and gender categories. The sensory characteristics evaluated were game meat aroma, juiciness, residual tissue, tenderness and game meat flavour. Age, gender and production region had an effect (P<0.05) on different sensory ratings of the meat. Whereas production region influenced (P<0.05) the game meat aroma, initial juiciness, sustained juiciness and residual tissue ratings of the meat, gender and age had a significant effect on only the residual tissue rating of the meat. An interaction (P<0.01) between age, gender and production region was observed for the tenderness attribute where the males from the Gariep Nature Reserve were the only gender that showed a significantly higher tenderness rating in the sub-adult than in the adult category. Sensory ratings were linearly correlated with certain physical and chemical attributes. Warner-Bratzler shear force (kg/1.27cm diameter) values were inversely correlated with the sensory attributes of tenderness (r=-0.70, P<0.01), residual tissue (r=-0.68, P<0.01) and sustained juiciness (r=-0.43; P<0.05). Age related effects on perceived tenderness were minor in comparison with pH effects. As the pH(24) of the meat increased, tenderness (r=-0.46, P<0.05) and sustained juiciness (r=-0.54, P<0.05) decreased significantly. No significant linear correlations were observed between the intramuscular fat (IMF) content and the sustained juiciness ratings of the meat. It can be concluded that production region had some influence on sensory characteristics of springbok meat, whilst the influence of age and gender were negligible. PMID- 22061258 TI - Meat quality of lambs of indigenous dairy Greek breeds as influenced by dietary protein and gastrointestinal nematode challenge. AB - The effect of dietary protein and gastrointestinal (GI) parasitism on growth and meat quality of lambs was assessed using 60 animals. The lambs were randomly allocated to one of three treatment groups (n=20): group A, which served as control, group B that was regularly treated with albendazole and group C, which was given supplementary feeding with dietary protein. The three groups of lambs grazed into a pasture (Lolium perenne), which was contaminated with L(3) larvae of GI nematodes. Lamb growth and condition score were assessed at 21-day intervals. After 126 days grazing all lambs were slaughtered and their carcasses were assessed for conformation and fatness and their ultimate pH was measured. Four carcasses from each group were randomly selected for meat quality measurements including physical analysis as well as colour, moisture, total fat, protein content and fatty acid composition. Parasitic challenge was assessed by means of faecal egg counts of lambs, pasture larvae and numbers of adult nematodes in the GI tract of lambs at slaughter. Growth rate of group B was higher (P<0.01) than that of group A and resulted in significantly (P<0.01) heavier carcasses. The produced carcasses had similar fatness, but differed significantly (P<0.05), in their conformation; carcasses of group C scored higher than either those of group B or group A, respectively. There was a significant difference in the colour attributes (L(*)) with group A being significantly lighter (P<0.05) and in pH (P<0.01); Group B had the highest values. Carcasses of group C had the highest (P<0.05) amounts of intermuscular fat compared to those of group B and A, respectively. The proportion of C16:1n-7 and C18:2n-6 was higher (P<0.05) in subcutaneous fat tissue whereas the proportion of C18:0 was higher (P<0.05) in muscle tissue. In conclusion, the present results showed that the increased protein content in the diet of growing lambs, grazing on a pasture infected with GI nematode larvae, resulted in the production of acceptable carcasses. PMID- 22061259 TI - Influence of slaughter season and muscle type on fatty acid composition, conjugated linoleic acid isomeric distribution and nutritional quality of intramuscular fat in Arouquesa-PDO veal. AB - The effects of the slaughter season and muscle type on lipid and conjugated linoleic acid (CLA) contents, fatty acid composition and isomeric profile of CLA in Arouquesa veal, from calves reared according to the specifications of the protected designation of origin (PDO), were assessed. Arouquesa purebred calves (n=31) were raised in a traditional production system, slaughtered in early autumn (October) or late spring (June), and the longissimus dorsi and semitendinosus muscles were sampled for analysis. Arouquesa-PDO veal only showed seasonal differences in the levels of some minor fatty acids (16:1c9, 17:1c9, 18:1t, 18:3n-3, 20:0 and 22:4n-6) and CLA isomers (t12,t14, t9,t11 and c11,t13). Furthermore, significant interactions between the slaughter season and muscle type were obtained for several fatty acids and CLA isomers, total lipids and CLA, and the PUFA/SFA ratio. In both seasons, veal-PDO depicts values of pasture-fed cattle. From a human nutritional perspective, veal-PDO in both slaughter seasons has relatively high CLA contents and percentages of the c9,t11 CLA isomer, which is favourable, while the n-6/n-3 ratios are within the recommended values for the human diet. In conclusion, the results suggest that intramuscular fat in Arouquesa-PDO veal has high nutritional value throughout the year. PMID- 22061260 TI - Antilisterial activity of lactic acid bacteria isolated from "Alheiras" (traditional Portuguese fermented sausages): In situ assays. AB - A total of 226 lactic acid bacteria (LAB) isolated from "Alheira", a traditional Portuguese fermented sausage, were screened for antagonistic activity against some pathogenic microorganisms, including Listeria monocytogenes. The objective was to isolate LAB with antibacterial activity from "Alheiras" and to select strains that could be used in "Alheira" production. Isolates displaying antibacterial activity against Listeria innocua and L. monocytogenes were investigated for the nature of the antibacterial compounds active against these microorganisms. Results showed that two LAB cultures retained activity in the supernatants after neutralization and catalase treatment. These two strains were both identified as Pediococcus pentosaceus. The final aim of this work was to test the antilisterial activity of these two strains during storage of "Alheira mass" (sterilized), at 4 degrees C. The growth of L. innocua population was significantly suppressed in the paste of "Alheira" when the samples were co inoculated with the LAB strains, in comparison with the paste only inoculated with L. innocua or co-inoculated with a bacteriocin negative strain of Ped. pentosaceus (ca. 1*10(7)CFU/g after 28 days of incubation). PMID- 22061261 TI - Loading 3-deazaneplanocin A into pegylated unilamellar liposomes by forming transient phenylboronic acid-drug complex and its pharmacokinetic features in Sprague-Dawley rats. AB - 3-Deazaneplanocin A (DZNep) is an attractive epigenetic anticancer agent through the inhibition of the cellular enhancer of zeste homolog 2 (EZH2) protein. The purpose of this study was to improve the pharmacokinetic characteristics of DZNep in vivo through developing a unilamellar pegylated liposomal formulation encapsulating DZNep (L-DZNep). A remote-loading method in the presence of phenylboronic acid (R-w-PBA) was developed to stably encapsulating DZNep inside liposomes (encapsulation efficiency=50.7% at molar ratio of 1:10 of drug to lipids) through forming a transient PBA-DZNep complex. The pharmacokinetics of L DZNep was investigated in Sprague-Dawley rats. In comparison with free drug, encapsulation of the DZNep in pegylated liposomes resulted in 99.3% reduction of the plasma clearance, whereas it increased the elimination half-life from 1.1 h to 8.0 h and the area under the plasma concentration curve by 138-fold. These findings demonstrate a novel approach (R-w-PBA method) through the development of L-DZNep, which may be extensively applied for the encapsulation of hydrophilic nucleoside analogs containing vicinal hydroxyl groups and protonable amino in the pegylated liposomes. Additionally, the pegylated liposomes could effectively prolong the retention of DZNep in the systemic circulation and therefore is highly likely to increase the DZNep's tumor localization. PMID- 22061262 TI - Nanoparticulate lipid dispersions for bromocriptine delivery: characterization and in vivo study. AB - The physico-chemical properties and in vivo efficacies of two nanoparticulate systems delivering the antiparkinsonian drug bromocriptine (BC) were compared in the present study. Monoolein Aqueous Dispersions (MADs) and Nanostructured Lipid Carriers (NLCs) were produced and characterized. Cryogenic transmission electron microscopy (cryo-TEM) and X-ray diffraction revealed the morphology of MAD and NLC. Dimensional distribution was determined by Photon Correlation Spectroscopy (PCS) and Sedimentation Field Flow Fractionation (SdFFF). In particular, BC was shown to be encapsulated with high entrapment efficiency both in MAD and in NLC, according to SdFFF combined with HPLC. Two behavioral tests specific for akinesia (bar test) or akinesia/bradykinesia (drag test) were used to compare the effects of the different BC formulations on motor disabilities in 6-hydroxydopamine hemilesioned rats in vivo, a model of Parkinson's disease. Both free BC and BC NLC reduced the immobility time in the bar test and enhanced the number of steps in the drag test, although the effects of encapsulated BC were longer lasting (5h). Conversely, BC-MAD was ineffective in the bar test and improved stepping activity in the drag test to a much lower degree than those achieved with the other preparations. We conclude that MAD and NLC can encapsulate BC, although only NLC provide long-lasting therapeutic effects possibly extending BC half-life in vivo. PMID- 22061263 TI - A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-beta25-35-treated rats following intranasal administration. AB - Because of the immunogenicity and toxicity in vivo of large molecules such as lectins, the application of these molecules is remarkably restricted in drug delivery systems. In this study, to improve the brain drug delivery and reduce the immunogenicity of traditional lectin modified delivery system, Odorranalectin (OL, 1700 Da), a novel non-immunogenic small peptide, was selected to establish an OL-modified cubosomes (Cubs) system. The streptavidin (SA)-conjugated Cubs were prepared by incorporating maleimide-PEG-oleate and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothiolane thiolated SA; mono-biotinylated OL was then coupled with the SA-modified Cubs. The OL-decorated Cubs (OL-Cubs) devised via a non-covalent SA-biotin "bridge" made it easy to conjugate OL and determine the number of ligands on the surface of the Cubs using sensitive chemiluminescent detection. Retention of the bio-recognitive activity of OL after covalent coupling was verified by hemagglutination testing. Nose-to brain delivery characteristic of OL-Cubs was investigated by in vivo fluorescent biodistribution using coumarin-6 as a marker. The relative uptake of coumarin carried by OL-Cubs was 1.66- to 3.46-fold in brain tissues compared to that incorporated in the Cubs. Besides, Gly14-Humanin (S14G-HN) as a model peptide drug was loaded into cubosomes and evaluated for its pharmacodynamics on Alzheimer's disease (AD) rats following intranasal administration by Morris water maze test and acetylcholinesterase activity determination. The results suggested that OL functionalization enhanced the therapeutic effects of S14G-HN-loaded cubosomes on AD. Thus, OL-Cubs might offer a novel effective and noninvasive system for brain drug delivery, especially for peptides and proteins. PMID- 22061264 TI - Mycobacterial disease in a population of 339 cats in Great Britain: II. Histopathology of 225 cases, and treatment and outcome of 184 cases. AB - This study investigated 339 cases of feline mycobacterial infection, with histopathology findings from 225 cases, and treatment and outcome information from 184 cases. Tissue samples from cats with cutaneous lesions or suspicious masses at exploratory laparotomy were submitted to the Veterinary Laboratories Agency for mycobacterial culture over a 4-year period to December 2008. The study reviewed the files for information about histopathology, treatment and outcome, and blindly reviewed histopathological changes (including staining for acid-fast bacteria [AFB]) in a sub-set of 45 cases. When a cat is suspected of having a mycobacterial infection, accurate identification of the species involved helps to determine possible treatment options and prognosis. The study confirmed that histopathology and the presence of AFB are useful tools in the recognition of mycobacterial infection. Unfortunately, they did little to help determine the species of mycobacteria involved. The study identified a group of cats that were negative for AFB at the primary laboratory, but from which mycobacteria could be cultured; commonly Mycobacterium bovis or Mycobacterium microti. The study also identified a group of cats which where culture negative, despite typical signs of mycobacterial infection and positive AFB staining. Many cases responded favourably to treatment (56% of the cases where information was available), and many cats gained complete remission (42%). However, relapses were common (64%) and often followed by pulmonary and/or systemic spread that may have resulted from treatment with short courses of single drugs. This study shows that the diagnosis and treatment of feline mycobacteriosis is complex and challenging. PMID- 22061265 TI - Computational design of high-affinity epitope scaffolds by backbone grafting of a linear epitope. AB - Computational grafting of functional motifs onto scaffold proteins is a promising way to engineer novel proteins with pre-specified functionalities. Typically, protein grafting involves the transplantation of protein side chains from a functional motif onto structurally homologous regions of scaffold proteins. Using this approach, we previously transplanted the human immunodeficiency virus 2F5 and 4E10 epitopes onto heterologous proteins to design novel "epitope-scaffold" antigens. However, side-chain grafting is limited by the availability of scaffolds with compatible backbone for a given epitope structure and offers no route to modify backbone structure to improve mimicry or binding affinity. To address this, we report here a new and more aggressive computational method backbone grafting of linear motifs-that transplants the backbone and side chains of linear functional motifs onto scaffold proteins. To test this method, we first used side-chain grafting to design new 2F5 epitope scaffolds with improved biophysical characteristics. We then independently transplanted the 2F5 epitope onto three of the same parent scaffolds using the newly developed backbone grafting procedure. Crystal structures of side-chain and backbone grafting designs showed close agreement with both the computational models and the desired epitope structure. In two cases, backbone grafting scaffolds bound antibody 2F5 with 30- and 9-fold higher affinity than corresponding side-chain grafting designs. These results demonstrate that flexible backbone methods for epitope grafting can significantly improve binding affinities over those achieved by fixed backbone methods alone. Backbone grafting of linear motifs is a general method to transplant functional motifs when backbone remodeling of the target scaffold is necessary. PMID- 22061266 TI - An aptamer beacon responsive to botulinum toxins. AB - Sixty candidate DNA aptamers were developed against botulinum neurotoxin (BoNT) type A light chain (LC) from ten rounds of selection, resulting in several identical sequences. Secondary structures of the identical aptamers were compared to structures of previously reported BoNT A DNA aptamers. A series of ten candidate loop structures were selected from this comparison as potential binding pockets and aptamer beacons. These candidate beacons were synthesized with 5'-TYE 665 and 3'-Iowa Black quencher labels for comparison of fluorescence levels as a function of BoNT A LC concentration. Only three of the ten candidates exhibited any fluorescence response to increasing levels of BoNT A LC. However, of the two most responsive candidates, one represented a subset loop of the larger more intensely fluorescent double-looped structure, designated Beacon 10. This beacon yielded a lower limit of detection of 1 ng/mL in buffer using a spectrofluorometer and a portable handheld fluorometer, but also responded substantially to BoNT A, B, E holotoxins and heavy or light chain components even in a dilute soil suspension, but not in 50% human serum. Beacon 10 did not respond strongly to a variety of other divergent peptides, suggesting that it is relatively specific to the level of botulinum toxins and is only useful for environmental testing. Beacon 10 also shared short sequence segments with other published BoNT aptamer DNA sequences, suggesting that these may be points of physical contact between the aptamers and BoNTs. PMID- 22061267 TI - Electrical performance of low cost cathodes prepared by plasma sputtering deposition in microbial fuel cells. AB - Microbial fuel cells (MFCs) could potentially be utilized for a variety of applications in the future from biosensors to wastewater treatment. However, the amount of costly platinum (Pt) used as a catalyst should be minimized via innovative deposition methods such as sputtering. In addition, alternative and low-cost catalysts, such as cobalt (Co), should be sought. In this study, ultra low Pt or Co cathodes (0.1 mg cm(-2)) were manufactured by plasma sputtering deposition and scanning electron micrographs revealed nano-clusters of metal catalyst in a porous structure favorable to the three-phase heterogeneous catalytic reaction. When operated in single-chamber air-cathode MFCs, sputtered Co cathodes generated on average the same power as sputtered-Pt cathodes (0.27 mW cell(-1)) and only 27% less than conventional Pt-ink cathodes with a catalyst load 5 times higher (0.5 mg cm(-2)). Finally, microscopy and molecular analyses showed evidence of biocatalysis activity on metal-free cathodes. PMID- 22061268 TI - Electrical impedance spectroscopy measurements using a four-electrode configuration improve on-line monitoring of cell concentration in adherent animal cell cultures. AB - This paper describes the improvement in the use of electrical impedance spectroscopy (EIS) for animal cell concentration monitoring of adherent cultures by using a four-electrode configuration instead of the commonly used two electrode configuration. This four-electrode configuration prevents cell concentration measurements from external masking effects such as the electrode covering ratio, the degree of cellular adherence to the electrodes and the impedance of the measuring electrodes. Cell concentration was monitored using both four-electrode and two-electrode configurations in vero cell and human mesenchymal stem cell cultures in order to analyze the attained improvement in two cell lines with opposite growth characteristics. The experiments performed with vero cell cultures evidenced that the four-electrode configuration enables cell concentration measurements along all culture phases, even once the culture reached cell confluence (over 2*10(5) cells/cm(2)), confirming that this configuration is less effected by all the external influences. The experiments performed with human mesenchymal stem cells demonstrated good sensitivity of the measurement at very low cell concentrations, as well as a very good robustness all over the 12-days experiment. Finally, off-line cell measurements during cell cultures proved good accuracy of impedance measurements carried out with a four electrode configuration along all cell growth phases, enabling determination of relevant cell growth parameters. PMID- 22061269 TI - The rs553668 polymorphism of the ADRA2A gene predicts the worsening of fasting glucose values in a cohort of subjects without diabetes. A population-based study. AB - AIMS: Single-nucleotide polymorphisms in the human ADRA2A gene have been associated with increased risk of Type 2 diabetes. The associations between the rs553668 polymorphism and fasting glucose concentrations both cross-sectionally and longitudinally after 6-year follow-up were evaluated in an adult Caucasian population-based cohort. METHODS: From a cohort of 1658 individuals, after excluding patients with diabetes, those who died and those whose blood samples were not available for genotyping, data of 1345 individuals were analysed. RESULTS: Subjects homozygous for the A allele showed significantly increased baseline fasting glucose values and a significant worsening of fasting glucose (beta = 0.48; 95% CI 0.10-0.86) and insulin secretion (beta =-20.75; -32.67 to 8.82 for homeostasis model assessment for beta-cell function) at follow-up by using generalized estimating equations. Incidence of impaired fasting glucose and diabetes was almost twofold higher in subjects homozygous for the A allele (respectively: incident impaired fasting glucose 7.6-8.2, 16.1%, incident diabetes 1.7-2.3, 3.2% in GG, AG, AA carriers). CONCLUSIONS: Our results suggested that the rs553668 polymorphism is associated with glucose worsening in subjects without diabetes at baseline. PMID- 22061270 TI - Genetic variation in serotonin transporter function affects human fear expression indexed by fear-potentiated startle. AB - The serotonin transporter (SERT) plays a crucial role in anxiety. Accordingly, variance in SERT functioning appears to constitute an important pathway to individual differences in anxiety. The current study tested the hypothesis that genetic variation in SERT function is associated with variability in the basic reflex physiology of defense. Healthy subjects (N=82) were presented with clearly instructed cues of shock threat and safety to induce robust anxiety reactions. Subjects carrying at least one short allele for the 5-HTTLPR polymorphism showed stronger fear-potentiated startle compared to long allele homozygotes. However, short allele carriers showed no deficit in the downregulation of fear after the offset of threat. These results suggest that natural variation in SERT function affects the magnitude of defensive reactions while not affecting the capacity for fear regulation. PMID- 22061271 TI - Effects of electrical stimulation, boning-temperature and conditioning mode on display colour of beef meat. AB - The effects of electrical stimulation of hot-boned (ESHB) bovine longissimus dorsi muscle, followed by vacuum packaging with different temperature/time regimes and storage in aerobic conditions, compared with cold-boned treatment (CB), on colour characteristics was assessed. No significant difference in haeminic iron content was noted between ESHB and CB meat. The opacity was more pronounced in ESHB meat vacuum packaged and incubated at 37 degrees C. This treatment (37 degrees C/4 h) allowed a lighter and brighter red meat colour with a higher level of contamination which was always acceptable. The worst results for colour characteristics were obtained with ESHB meat conditioned rapidly at 2 degrees C. No differences were noted between ESHB meat conditioned at 25 degrees C and CB meat. To explain these discrepancies between treatments about colour characteristics, where muscle translucency is largely involved, differences in enzymic reducing activity and denaturation of sarcoplasmic proteins during glycolysis must be implicated. PMID- 22061272 TI - Effect of electrical stimulation on the rheological properties of rabbit skeletal muscle. AB - The effect of electrical stimulation on the rheological properties of rabbit skeletal muscle after death was investigated. The extensibility of electrically stimulated psoas muscles decreased more rapidly than that of non-stimulated muscles. For raw non-stimulated longissimus thoracis muscles excised from the carcasses immediately after slaughter, the penetration force required was greatest 24 h after slaughter and then decreased slightly after 168 h. The corresponding force for stimulated longissimus thoracis muscles increased to a maximum in 12 h and then decreased to values less than non-stimulated muscles. However, in the case of raw longissimus thoracis muscles whichhad been attached to the skeleton until measurement, there was no significant difference in penetration force between stimulated and non-stimulated muscles. In cooked muscles, electrical stimulation resulted in lower penetration forces at 24 h post mortem, but on further storage the differences decreased. PMID- 22061273 TI - The solubilization of myofibrillar proteins by calcium ions. AB - The effect of elevated levels (30 mm) of Ca(2+) and other divalent metals ions on rabbit psoas myofibrils was studied to determine whether these caused solubilization of structural proteins and if so whether the effect was due to salting-in or to proteolytic fragmentation resulting from activation of calpains. Incubation of myofibrils in 30 mm CaCl(2) at either pH 5.6 or 7.0 did not cause any apparent solubilization of the major Z-disc proteins, but there was an immediate ( < 1 min) solubilization of C-protein and troponin I together with small amounts of Mr 80 000 protein, troponin T and tropomyosin. Longer incubations with CaCl(2) extracted little additional C-protein but there was a steady increase with time in the solubilization of proteins with Mr values of 45 000 and 42 000, troponin T, tropomyosin and troponin I. Another high molecular weight protein of Mr 3-400 000 was extracted at pH 7.0 but not at pH 5.6. Similar results were obtained on incubation with 30 mm MgCl(2). In contrast to these findings, the same concentration of ZnCl(2) caused no detectable solubilization of myofibrillar proteins. The inclusion of proteinase inhibitors, E64, leupeptin, pepstatin or PMSF did not prevent the immediate solubilization of proteins. This showed that the solubilization of the proteins by Ca(2+) ions was due to salting in rather than to proteolytic action by calpains. PMID- 22061274 TI - Effects of pithing on pH, creatine phosphate and ATP-related compounds of beef Psoas major and Longissimus dorsi muscles. AB - The effects of pithing at slaughter on meat quality were studied in M. longissimus dorsi (LD muscle) and M. psoas major (PM muscle) from steers. Ten steers, half of them pithed and the others not pithed at slaughter, were used for determining pH values and concentrations of creatine phosphate (CP), adenosine triphosphate (ATP) and its breakdown products in the muscles at 2.0 h post mortem. CP was not detected in any PM muscles from pithed steers and no significant differences were observed between pithed and non-pithed steers on the mean values of pH and any compounds, but significant differences were observed in the variance of pH value, ATP, (inosine monophosphate IMP) and inosine levels in PM muscles and of (adenosine diphosphate ADP) and IMP levels in LD muscles. When two steers with excitable temperament were excluded from the pithed group significant differences of variance between the treatments were observed only in PM muscles. The pithing procedure thus affects the levels of pH and of some of the ATP-related compounds in the PM but not in LD muscles. PMID- 22061275 TI - Lipid composition of pork muscle in relation to the metabolic type of the fibres. AB - The aim of this study was to investigate the relationships between lipid composition and metabolic type of the muscles in pork. Five muscles (Longissimus dorsi, Biceps femoris, Psoas major, Trapezius and Masseter) were chosen in order to cover a broad range of metabolic type. The results showed that: PMID- 22061276 TI - The estimation of the age of cattle by the measurement of thermal stability of tendon collagen. AB - Two measures of the thermal stability of tendon collagen (thermal transition temperature and isometric tension) have been studied as a function of age of cattle. The aim was to assess their potential for estimating the age of an animal from which a sample of meat originated. The variation in thermal transition temperature between animals was too large for reliable estimation of animal age by this method. The maximum isometric force generated during heating of strips of tendon from the longissimus dorsi muscle was found to increase linearly with age. Measurements of isometric tension at pH 6.0 had the least variation between animals from 2 to 16 years of age, but were not suitable for younger animals. At pH 7.5, the entire age range could be measured, and although the variation between animals was increased, the accuracy of the age determination still compared favourably with that of dentition. PMID- 22061277 TI - The relationship between animal age and the thermal stability and cross-link content of collagen from five goat muscles. AB - The thermal stability of intramuscular collagen, as determined using differential scanning calorimetry, was measured in five muscles from 75 goats with known birth dates ranging in age from one day to 13 years. The collagen cross-link pyridinoline, and the collagen-associated, and putative cross-link, Ehrlich Chromogen were also measured. Five different muscles were examined and the effects of age compared to those found in the tendon of the longissimus dorsi muscle. The differences between intramuscular collagen and tendon collagen were found to be much greater than those between the intramuscular collagens of different muscles. Intramuscular collagen is more thermally stable than tendon collagen due to higher levels of heat-stable cross-links. However the increase in thermal stability of intramuscular collagen with age could not be explained simply in terms of the cross-links measured. PMID- 22061278 TI - Cattle at risk for dark-cutting beef have a higher proportion of oxidative muscle fibres. AB - The aim of this investigation was to compare muscle fibre type characteristics in dark-cutting (DFD) and normal beef animals. Three categories of animal were used in this investigation: 9 DFD bulls, 10 DFD steers and 10 normal bulls. For each animal, frozen sections of longissimus dorsi muscle were stained histochemically. The results showed that there were proportionately more slow, oxidative (SO) fibres in DFD bulls and DFD steers than in normal bulls. As far as fast, glycolytic (FG) fibres were concerned DFD bulls contained fewer of this type than DFD steers and normal bulls. When the results on fibre proportions were combined with those on mean fibre cross-sectional areas it was found that both DFD groups contained a smaller proportion of muscle exhibiting FG characteristics than normal bulls. Furthermore, the combination of all oxidative fibres, i.e. SO and fast, oxidative, glycolytic (FOG) fibres, showed that, both by numbers and relative areas, the two DFD groups (especially DFD bulls) exhibited significantly more oxidative metabolism in the longissimus dorsi muscle than the normal animals. PMID- 22061279 TI - Theoretical strain ranges in raw meat. AB - Rheological data obtained in a compression test of raw meat samples are expressed on the basis of actual meat length ratio which takes into account pre-rigor strains, during contraction or stretching, and post-rigor strains occurring during post-rigor contraction or during the compression test. The relationship between the deformation of collagenous fibres and that of meat sample gives the critical compression ratio at which the collagenous fibres undergo tension. A theoretical curve is given to explain the variation in the critical compression ratio with initial state of sample. The curve is used to define theoretical strain ranges in which predominantly one structure (muscle fibres, elastin fibres or collagenous fibres) is involved and consequently can be analysed. PMID- 22061280 TI - Ash and calcium as measures of bone in meat and bone mixtures. AB - Bone content of mechanically recovered meat is usually controlled by setting calcium limits, but these limits may allow more bone in some products because calcium content of fresh bone is variable. Studies involving deposition of energy, nutrients, and minerals are also dependent on ash or calcium to determine bone content of carcasses. However, ash and calcium, which is 37% of bone ash, varies by age of animal, presence or absence of tissues such as marrow or cartilage that are associated with bone, and state of bone hydration. Literature that reports ash content of bone and factors associated with its variability is the focus of this review. Based on the literature reviewed, a conversion factor of 4.5 for calcium percentage to fresh cortical bone percentage from round bones of cows, fed beef, lambs, pigs and hens is recommended. A conversion factor of calcium percentage to fresh bone percentage of 5.0 is recommended for all veal and broiler bones and for flat bones. PMID- 22061281 TI - Effect of electrical stimulation on protease activity and tenderness of M. longissimus from cattle with different proportions of Bos indicus content. AB - The effect of electrical stimulation on protease activity (at approx. 3 h postmortem), sensory tenderness scores and shear force was determined on M. longissimus samples from three Bos indicus genotypes (0% Hereford, 50% Brahman*Hereford and 100% Brahman). The samples were divided and aged for 1 or 30 days. Electrical stimulation resulted in a general reduction in calpastatin activity suggesting that it accelerated proteolysis. Calpastatin activity increased commensurate with increasing Bos indicus content. Several significant interactions were shown, the most relevant of these was the interaction between Bos indicus content*electrical stimulation. In contrast to the other genotypes, calpain I and calpain II activities were shown to increase (significant for calpain II only) following stimulation in the purebred Brahmans (100%). There was a significant reduction in tenderness with increasing Bos indicus content. However, breed differences in shear force were reduced by electrical stimulation. The improvement in shear force following ageing was smaller for stimulated carcasses compared to the controls. This tends to reinforce the premise that electrical stimulation accelerates proteolysis. The results of this study show clear genotypic differences in proteolytic activity and tenderness. However, electrical stimulation can be employed to reduce breed differences in tenderness of the M. longissimus. PMID- 22061282 TI - Determination of RN(-) phenotype in pigs at slaughter-line using visual and near infrared spectroscopy. AB - The specific characteristics of meat from the Hampshire breed of pig, including high glycogen content and low ultimate pH and technological yield, have been associated with the dominant RN gene. In Sweden, purebred Hampshire or Hampshire x Yorkshire is often used as terminal sire in the three-way crosses used for pig meat production. For the industry producing cured and cooked hams there is a need to detect the RN(-) carriers of the pigs early post mortem in order to select non carriers for ham production. In the present study, the possibility of separating RN(-) carriers from non-carriers using a combination of visual and near-infrared (NIR) spectroscopic measurements in reflectance mode through a fibre-optic probe has been studied on commercial pigs in a slaughterhouse. The NIR measurements were performed 30 min post-mortem. Sixty-three animals were considered to be carriers and 33 animals non-carriers based on their glycolytic potential in M. semimembranosus (above 200 MUmol/g for RN(-)rn(+) and below 180 MUmol/g for rn(+)rn(+)). By using NIR together with classification with neural networks, RN( ) carriers could be separated from non-carriers. None of the carriers and only four non-carriers of the RN gene were misclassified as carriers of the RN gene. The ultimate pH could be predicted using linear partial least squares regression with a correlation coefficient of 0.57 and an accuracy of 0.074 root mean square error of prediction. PMID- 22061283 TI - Variation of residual glycogen-glucose concentration at ultimate pH values below 5.75. AB - The aim of this study was to investigate the relationship between residual carbohydrate (glycogen-glucose) concentration and ultimate pH of beef. Ultimate pH of longissimus dorsi (LTL), gluteus medius (GM) and semimembranosus (SM) muscles was determined from the left side of 133 Ayrshire bull carcasses. Corresponding muscle samples (about 3 g) were obtained from the sites of the pH measurements. The relationship was curvelinear. At low pH values the total range of residual glucose concentration was up to 73 mmol/kg, maximum being 83 and minimum 10 mmol/kg. The concept of medium-stress beef, where the combination of low ultimate pH and low residual glycogen is an indication of diminished glycogen content at the time of slaughter, is introduced. The potential negative effects of low residual glycogen concentration on the shelf-life of ground beef is discussed. PMID- 22061284 TI - Effect of various concentrations of lactic acid and sodium chloride on selected physico-chemical meat traits. AB - The aim of the research was to determine water binding and holding capacity and to measure the force and work of penetration of minced pork and beef cured with brine of varying concentrations of sodium chloride and lactic acid and then heated. M. biceps femoris was cut out from chilled pork and beef carcasses three times from each species. Minced meat was subjected to curing. Each of the 20 experimental treatments resulted from appropriate combinations of salt (0.0-2.0%) and lactic acid (0.0-1.5%). The individual concentrations of these two compounds differed by 0.5%. The addition of the curing brine containing only sodium chloride or only lactic acid caused an increase of water holding and binding capacity. The additions of curing brines containing various concentrations of mixtures of salt and acid cause lowering of water holding and binding capacity. Higher penetration force and work had to be applied for pork than for beef samples. With the increase of salt and lactic acid concentrations applied together, after the initial increase of the penetration force and work, their values were found to decrease at higher concentrations of mixtures of these substances in meat. PMID- 22061285 TI - The effect of sodium chloride content and temperature on pork meat isotherms. AB - The knowledge of sorption isotherms is essential for understanding the drying process. Throughout the dry cured meat process, changes occur in the NaCl content and temperature on the surface of meat products. The aim of this study was to obtain the desorption isotherms from raw and salted meat at different air temperatures and NaCl content. The desorption characteristics were studied in the relative humidity range of 11.2 to 94.5 % at storage temperatures of 5, 13 and 26 degrees C and at 0, 8, 20 and 30% (dm) of added salt (NaCl). The salted meat samples isotherms at 26 degrees C shows a breaking point between water activities (a(w)) of 0.70 and 0.75. At a(w) lower than 0.70, NaCl content and temperature have only a slight effect on water content equilibrium. At a(w) above 0.75, water content equilibrium increased with the increase in NaCl content and the decrease in temperature. A significant NaCl*Temp interaction was detected at a(W) 0.903 and 0.946. PMID- 22061286 TI - Screening of commercial meat starter cultures at low pH and in the presence of bile salts for potential probiotic use. AB - The survival of lactic acid bacterial strains from eight meat starter cultures under conditions similar to those in the gastrointestinal tract was determined. The conditions in stomach were simulated by using pH 1-5 phosphate-buffered saline. The conditions in small intestine were simulated by using MRS broth over a pH range 4-7 and two bile salt concentrations (0.15% and 0.30%). The survival capacity at pH 3 was strain dependent. 0.30% bile salts were critical for screening bile salt tolerant strains at pH 6. Strains of Lactobacillus sake (RM10) and Pediococcus acidilactici (P2) had the best survival capacities under acidic conditions and at the higher concentration of bile salts. PMID- 22061287 TI - The effect of cooking temperature on mechanical properties of whole meat, single muscle fibres and perimysial connective tissue. AB - The structural changes in beef semitendinosus caused by cooking were studied by performing tensile tests of the isolated meat components (i.e. single muscle fibres and perimysial connective tissue) and related to the toughness of the whole meat. Whole meat toughness was found to increase in two separate phases upon cooking from 40-50 degrees C, and again from 60 to 80 degrees C with a decrease in meat toughness between 50 and 60 degrees C, in agreement with previous studies. The changes in whole meat toughness at temperatures below 60 degrees C were found to correspond to changes in the mechanical properties of the perimysial connective tissue, whereas changes of whole meat toughness at temperatures above 60 degrees C were found to correspond to increased breaking strength of single muscle fibres. The myofibrillar component explained approximately 47% of the variation in whole meat toughness upon cooking whereas inclusion of the connective tissue component increased the goodness of fit. PMID- 22061288 TI - The effect of stunning method on the incidence of PSE meat and haemorrhages in pork carcasses. AB - Two commercial pig abattoirs (A and B) equipped with a head-only and head-to chest electrical stunning systems, and two (C and D) equipped with compact carbon dioxide (CO(2)) stunning systems, were visited during 3 days to evaluate the effects of the stunning system on meat quality and haemorrhages. Meat quality was evaluated by measuring muscle electrical conductivity (PQM) and colour (Minolta Chromameter) at 2 and 7 h post mortem (abattoirs A and C, and B and D, respectively). PQM and colour were measured in 2486 and 2321 loins respectively. Also ultimate pH (pHu) was measured in 2395 loins at 24 h post mortem. Haemorrhages were evaluated by recording the incidence of petechiae, ecchymosis and haematomas, bone fractures were also recorded. A total of 1980 shoulders, 3943 loins, and 5438 hams were inspected. In the abattoirs equipped with the electrical stunning systems, a higher (P<0.05) incidence of potentially PSE meat (PQM>6) was found compared with the abattoirs equipped with CO(2) stunning. Likewise, the loins from electrically stunned pigs were paler than those from CO(2) stunned pigs (P<0.05). Electrical stunning increased the incidence of petechiae in the loin and the ham (P<0.05). No shoulder, loin or ham with bone fractures was found in the abattoirs studied. Therefore, CO(2) stunning reduces the incidence of PSE meat and of petechiae on muscle fascia of loins and hams, compared with electrical stunning. However, petechiae are not of great importance because they can be removed from the affected commercial cuts. PMID- 22061289 TI - The effect of the sticking method on the welfare of slaughter pigs. AB - A project was undertaken to investigate the causes of inadequate sticking encountered during a survey of pig abattoirs. The results of the investigation identified the length of the sticking (exsanguination) wound as a major contributor to the problem. Experimental abattoir trials conducted on slaughter pigs comparing two sticking lengths indicated that the rate of bleed out was delayed with short sticking wounds. In addition, information about the identity of blood vessels severed following sticking was obtained. The results indicate that following head-only electrical stunning, a relatively long sticking wound should provide better welfare in slaughter pigs. The study has also highlighted the health and safety problems for the operatives as well as the welfare concerns associated with manual application of electrical stunning. PMID- 22061290 TI - Minimum sodium nitrite levels for pinking of various cooked meats as related to use of direct or indirect-dried soy isolates in poultry rolls. AB - The relationship between sodium nitrite level and pinking was investigated in cooked meats, as measured by panel color score, acetone extraction of NO hemochrome, and instrumental redness values. Beef was less susceptible than poultry breast meat to nitrite-induced pinking. Minimum sodium nitrite level for pinking was 14, 4, 2, and 1 ppm for beef round, pork shoulder, turkey breast, and chicken breast, respectively. By regression analysis, minimum ppm nitrite for pinking=0.092 (ppm total pigment)+0.53 (R(2)=0.99). High levels of nitrate (>250 ppm as sodium nitrate) and nitrite (>45 ppm as sodium nitrite) were found in direct-dried (DD) soy isolates. Chicken breast rolls formulated with >2% DD soy were pink, but control rolls with 156 ppm sodium nitrate were not pink. Thus, it was concluded that nitrite was the primary pinking agent in DD soy. Indirect dried (ID) soy isolates contained <11 ppm sodium nitrite, which was insufficient for pinking in poultry rolls. PMID- 22061291 TI - Effect of dietary vitamin E supplementation, fat level and packaging on colour stability and lipid oxidation in minced beef. AB - The effect of addition of vitamin E (2025 IU animal(-1) day(-1)) to the diet of beef bulls on the colour stability and lipid oxidation of minced beef was studied. Control and enriched diets were provided for the last 136 days before slaughter. Batches of freshly minced meat were prepared containing approximately 1.3 and 22.2 wt% fat, respectively. Half of the samples of minced meat from control (CON) and supplemented (SUP) beef were packaged on trays with oxygen permeable over wraps and half in modified atmosphere (MA) packs (initial gas mixture: O(2)/CO(2)/N(2)=65/25/10). The minced beef was stored for 10 days at 7 degrees C in an illuminated environment. The SUP meat at both fat levels was consistently more resistant to lipid oxidation than was the CON meat. The additional vitamin E had a greater anti-oxidant effect for the lean meat product. MA packaging in comparison to the oxygen-permeable foil over-wrap did increase lipid oxidation, the effect being most pronounced for the CON meat. A sensory panel considered the colour of the lean SUP meat during display as more attractive than that of lean CON meat, irrespective of packaging. A similar effect was observed occasionally for the relatively fat minced meat. These subjective findings were confirmed by objective assessment of colour. The stability of the colour of the MA packed meat was better than that of the oxygen permeable foil-wrapped meat. Microbial growth patterns of enriched and control meat were similar. MA packaging retards the multiplication of mesophilic aerobic spoilage micro-organisms and Enterobacteriaceae. PMID- 22061292 TI - The use of discriminant analysis for the interpretation of the reflectance spectra of irradiated porcine M. longissimus dorsi. AB - Slices of porcine M. longissimus dorsi were packed in overwrap packs and subjected to irradiation (0 and 5 kGy) and then stored for 7 days at 4 degrees C. Reflectance spectra were measured on the outside surface and a freshly cut surface at 7 days post irradiation. The reflectance spectra were transformed to reflex attenuance, k/s and first and second difference spectra and subjected to discriminant analysis. Using discriminant analysis it was possible to establish a calibration equation to discriminate between the spectra of irradiated and unirradiated pork for both the outside and the inside surface. When the calibration model was used to predict the classification of new samples a 100% correct grouping was obtained for the freshly cut surface, however, for the outside surface the classification ranged from 87 to 100% correct depending on the mathematical transformation of the reflectance spectra. This shows the potential of colour measurements as a possible rapid initial screening test for the identification of irradiated pork. Evaluation of the first difference spectra to identify peak positions showed significant differences in peak positions between irradiated and unirradiated pork. The position of the peaks in the irradiated sample is discussed as lending support to the hypothesis of the carboxyhaem form as the irradiated pigment. PMID- 22061293 TI - The effect of ionising radiation on the colour of beef, pork and lamb. AB - The effect of irradiation (0 and 5 kGy) of beef, pork and lamb portions in retail overwrap packs and subsequent storage at 4 degrees C was studied in relation to colour changes. The colour of the exterior surface of beef and pork was measured on the same samples on each day of storage for up to 7 days post irradiation. On day 7 the colour of a freshly cut surface was measured. The colour of both the exterior and a freshly cut surface of lamb, in similar retail overwrap packs was measured at 2, 5 and 7 days, post irradiation, different samples being used on each day of measurement. L* values of irradiated beef increased significantly with storage and a* values for unirradiated samples decreased significantly with storage. For lamb there was a general increase in L* and h(o) values and a decrease in a*, b* and C* values with storage. Analyses of the day 7 data showed statistically significant effects for species on all CIELAB parameters. Irradiation resulted in significantly higher hue angle (h(o)) values and the a*, b* and C* values were significantly higher on the exterior than freshly cut surface. There were a number of statistically significant 2 factor and 3 factor interactions. The role of formation of a carboxyhaem pigment in the colour of irradiated meat is discussed. The problem of interpretation of pigment changes from CIELAB values is highlighted. PMID- 22061294 TI - The effect of ionising radiation on the colour of leg and breast of poultry meat. AB - The effect of irradiation (0 and 5 kGy) of chicken, goose and turkey breast and leg muscles and subsequent storage at 4 degrees C was studied in relation to colour changes. The colour of the outside surface was measured on the breast on each day of storage for up to 7 days post irradiation and for breast and leg and day 7. The colour of a freshly cut interior surface of both breast and leg was measured after 7 days storage. L* values of control and irradiated chicken, goose and turkey breast muscles changed little during storage post irradiation. The a* values for unirradiated goose breast were significantly higher than irradiated goose breast but declined to values similar to irradiated goose breast after 7 days of storage. The b* values for irradiated turkey breast were significantly higher than unirradiated turkey breast at all times post irradiation treatment. Analysis of variance was performed on the day 7 CIELAB values of breast muscle for the effects of species, surface and irradiation and their interactions. After 7 days storage a* values of poultry breast were higher on the freshly cut surface due to irradiation in all species, with decreases in hue angle due to irradiation. The a* values of leg of all species at 7 day post irradiation was significantly higher in the irradiated treatment than the controls. The results for the turkey leg indicate that this effect may be mainly due to higher a* values of the freshly cut surface. The possible role of carboxy form of the haem pigments as the irradiated pigment form is discussed. PMID- 22061295 TI - A transparent and transportable methodology for evaluating Data Linkage software. AB - There has been substantial growth in Data Linkage (DL) activities in recent years. This reflects growth in both the demand for, and the supply of, linked or linkable data. Increased utilisation of DL "services" has brought with it increased need for impartial information about the suitability and performance capabilities of DL software programs and packages. Although evaluations of DL software exist; most have been restricted to the comparison of two or three packages. Evaluations of a large number of packages are rare because of the time and resource burden placed on the evaluators and the need for a suitable "gold standard" evaluation dataset. In this paper we present an evaluation methodology that overcomes a number of these difficulties. Our approach involves the generation and use of representative synthetic data; the execution of a series of linkages using a pre-defined linkage strategy; and the use of standard linkage quality metrics to assess performance. The methodology is both transparent and transportable, producing genuinely comparable results. The methodology was used by the Centre for Data Linkage (CDL) at Curtin University in an evaluation of ten DL software packages. It is also being used to evaluate larger linkage systems (not just packages). The methodology provides a unique opportunity to benchmark the quality of linkages in different operational environments. PMID- 22061296 TI - Low-grade systolic murmurs in healthy middle-aged individuals: innocent or clinically significant? A 35-year follow-up study of 2014 Norwegian men. AB - OBJECTIVE: To determine whether a low-grade systolic murmur, found at heart auscultation, in middle-aged healthy men influences the long-term risk of aortic valve replacement (AVR) and death from cardiovascular disease (CVD). Setting and subjects. During 1972-1975, 2014 apparently healthy men aged 40-59 years underwent an examination programme including case history, clinical examination, blood tests and a symptom-limited exercise ECG test. Heart auscultation was performed under standardized conditions, and murmurs were graded on a scale from I to VI. No men were found to have grade V/VI murmurs. Participants were followed for up to 35 years. RESULTS: A total of 1541 men had no systolic murmur; 441 had low-grade murmurs (grade I/II) and 32 had moderate-grade murmurs (grade III/IV). Men with low-grade murmurs had a 4.7-fold [95% confidence interval (CI) 2.1-11.1] increased age-adjusted risk of AVR, but no increase in risk of CVD death. Men with moderate-grade murmurs had an 89.3-fold (95% CI 39.2-211.2) age-adjusted risk of AVR and a 1.5-fold (95% CI 0.8-2.5) age-adjusted increased risk of CVD death. CONCLUSIONS: Low-grade systolic murmur was detected at heart auscultation in 21.9% of apparently healthy middle-aged men. Men with low-grade murmur had an increased risk of AVR, but no increase in risk of CVD death. Only 1.6% of men had moderate-grade murmur; these men had a very high risk of AVR and a 1.5-fold albeit non-significant increase in risk of CVD death. PMID- 22061297 TI - Effect of replacing pork backfat with olive oil on processing and quality characteristics of fermented sausages. AB - Five types of fermented sausages were manufactured by traditional methods as follows: (i) one control (C) using 24% beef meat, 43% pork meat and 33% pork backfat; (ii) two L treatments by replacing 10% and 20%, respectively of pork backfat with liquid olive oil; and (iii) two E treatments by replacing 10% and 20%, respectively of pork backfat with olive oil incorporated as pre-emulsified fat (PEF) with soy protein isolate (SPI). There were no differences (p > 0.05) between treatments relating to pH, brine content, lactic acid bacteria and micrococci and staphylococci count, redness (a (*)) and chemical composition. The L and E treatments had higher lightness and yellowness values than the control. The L treatments had lower (p < 0.05) weight losses and higher (p < 0.05) TBA values and were softer (p < 0.05) than the control. The E treatments had higher (p < 0.05; weight losses, lower (p < 0.05) TBA values and similar hardness to the control. The L sausages had an unacceptable appearance. The E sausages had equally good appearance as well as firmness and odour and taste as the control. It is concluded up to 20% of pork backfat can be replaced with olive oil as PEF with SPI. In preliminary experiments, where 30% pork backfat was replaced with olive oil as PEF with SPI, the product was unacceptable. PMID- 22061298 TI - Comparative study of metabolic differentiation of foetal muscle in normal and double-muscled cattle. AB - Studies of the contractile differentiation of foetal muscles in normal and double muscled cattle have shown that double-muscled foetal muscles display comparative delayed contractile differentiation. We compared the metabolic differentiation of foetal muscles in normal and double-muscled cattle, for which no data were available. The semitendinosus (ST) muscle was excised from normal and double muscled cattle foetuses aged 110-260 days. Isocitrate dehydrogenase (ICDH) and lactate dehydrogenase (LDH) activities, respectively representative of aerobic oxidative and anaerobic glycolytic metabolism, were assayed. The five LDH isozymes were separated by electrophoresis under non-denaturing conditions and assayed by densitometry. ICDH activity was weaker in the ST of double-muscled foetuses than in that of normal ones throughout gestation, and it increased later in the double-muscled foetuses than in normal ones. In contrast, the LDH activity increased at 180 days in both. It was greater in the double-muscled beyond that time. The proportion of LDH-M subunit was higher at all foetal ages in the double muscled. Overall, these results show that: (1) the metabolic differentiation of muscle fibre occurs during the last third of foetal growth in both normal and double-muscled cattle; and (2) the differentiation of aerobic oxidative metabolism is delayed in double-muscled foetuses compared with normal ones. PMID- 22061299 TI - The effect of dietary vitamin E supplementation on drip loss of bovine Longissimus lumborum, psoas major and Semitendinosus muscles. AB - The effect of dietary vitamin E supplementation (2150 IU/head/day) on drip loss and related quality traits of bovine M. longissimus lumborum M. psoas major and M. semitendinosus was examined. The effect of vitamin E supplementation on drip loss seemed to depend on muscle studied. Drip loss of longissimus muscles was not significantly influenced, whereas supplemented semitendinosus muscles lost significantly less (p < 0.05) and supplemented psoas major muscles significantly more (p < 0.05) drip than did control counterparts. In both supplemented and control samples, sarcolemma failure occurred. No ultimate pH differences were detected between control and supplemented samples regardless of the muscle considered. In supplemented semitendinosus muscles, the decrease in drip loss was accompanied by an increase of sarcoplasmic protein solubility and sarcomere length. It is discussed that both these variables may be related to the stability of mitochondria and sarcoplasmic reticulum, as affected by dietary supplementation of vitamin E. However, this view deserves further investigation and more evidence is needed to establish the mechanism by which vitamin E influences drip loss. PMID- 22061300 TI - Lipolysis in dry cured sausages as affected by processing conditions. AB - Changes of phospholipids and free fatty acids during fermentation and ripening steps of the Spanish dry cured sausage ('salchichon') process have been analyzed by studying the effects of manufacturing conditions; namely starter addition, pre ripening and drying temperature. Phospholipid concentration of all types of samples considered (with or without starter, preripened or not) showed no important changes during fermentation, but different behaviour was observed during ripening in relation to sample type and drying temperature. At 8 degrees C concentrations did not change in sausages without starter and suffered a moderate decrease in samples with starter. At 16 degrees C the decrease was pronounced in samples without starter and much more in those with starter. Pre ripening had no effect on phospholipid concentration. Free fatty acids increase slightly with pre-ripening, but during fermentation pre-ripened samples showed no more variation, whereas in non-preripened samples an important increase was observed. These results were similar in samples with and without starter. During the ripening step, samples with starter dried at 8 degrees C showed a higher increase of free fatty acids than those without starter, with no influence of the pre-ripening. At 16 degrees C all samples showed a higher increase than any sample dried at 8 degrees C. The maximum was found with non-preripened samples without starter and the minimum with pre-ripened ones, also without starter. Sausages with starter showed an intermediate increase with no effect of pre ripening. PMID- 22061301 TI - Diet and growth effects in panel assessment of sheepmeat odour and flavour. AB - The effects of sheep age and diet on several odours and flavours are described. Ram lambs raised on ewe's milk then a corn-based diet were compared with lambs raised on milk and a pasture of grass/clover, six treatments in all. A seventh treatment comprised very old ewes maintained on pasture. Fat and lean from forequarters was minced and cooked together. Cooked lean was assessed for intensity by a sensory panel for 10 flavour attributes. Four showed significant (P < 0.01) treatment effects: 'sheepmeat', 'animal', 'liver', and 'poultry'. Sheepmeat flavour was highest in the slow-grown pasture-fed lambs. Animal flavour the flavour associated with the odour of confined livestock-showed a similar pattern with treatment. Liver flavour was highest in ewe meat, and the biochemical origin of this flavour is discussed. Eleven related odour attributes were assessed on the rendered fat with a novel olfactometer. Five attributes showed highly significant treatment effects for intensity (P < 0.001): animal and sheepmeat odours showed a similar distribution to the equivalent flavours; likewise cabbage and rancid odours were associated with the two slow-grown pasture treatments. A comparison of the odour and flavour statistics showed that the sense of smell was the more discriminating in sheepmeat assessment, and also confirmed that fat was the true source of sheepmeat odour/flavour. In respect of sheepmeat production for effective marketing, the data showed that at 90 days, a pastoral diet resulted in slightly enhanced odours when compared with a corn based diet. By 215 days, however, many undesirable odours were exacerbated. Since these older rams were more sexually developed, a sex rather than an age effect could not be excluded. Rendered fat from this work was further used in a companion study (Yang et al., 1997. Meat Sci., 45, 183-200) in an attempt to link individual volatile compounds to odour attributes. PMID- 22061302 TI - Fat-borne volatiles and sheepmeat odour. AB - The effects of lamb age and diet on volatiles from fat are described. Rendered fat from ram lambs raised on ewe's milk then a corn-based diet was compared with that from lambs raised on milk and a pasture of grass/clover, six treatments in all. An additional treatment comprised very old ewes maintained on pasture. Helium-borne volatiles of rendered fat were resolved on a DB5 gas chromatographic column and the mass spectra obtained. Long chain alka(e)nes like neophytadiene were dominant in pasture treatments especially where the lamb growth rate was slow. Branch chain fatty acids (4-methyloctanoic, 4-methylnonanoic and an unidentified acid) were also highest in these treatments. Longer chain aldehydes like 2-undecenal were good indicators of a grain diet. Hexanal, commonly associated with rancid odours, was unaffected by treatment. The diketone 2,3 octanedione was an excellent indicator of a pasture diet, as was 3-methylindole (skatole). Phenols showed complex relationships to treatments, but were generally more common in pasture treatments. Benzenethiol (thiophenol) was unaffected by treatment. Inspection of principal component analysis plots identified 10 volatile compounds as contenders for the cause of sheepmeat odour; branch chain fatty acids were confirmed as the leading chemical class. There were indications that puberty or age caused an increase in the odorous 4-methylnonanoic acid. Animal odour-the odour of confined livestock-was clearly causally linked to 3 methylindole, a rumen breakdown product of tryptophan. 3-Methylindole was also responsible for rancid odour, rather than hexanal and its analogues. A hypothesis is advanced that links 2,3-octanedione formation to the enzyme lipoxygenase and linolenic acid, both abundant in green leafy tissue. Overall, the data confirm that sheepmeat odour/flavour is specifically linked to the branch chain fatty acids, and is probably exacerbated by pasture-derived 3-methylindole and alkyl phenols. PMID- 22061303 TI - Effect of stress-induced high post-mortem pH on protease activity and tenderness of beef. AB - Forty-four Swiss Brown young bulls were stressed by regrouping unfamiliar animals before slaughter. M. longissimus thoracis (6-9th ribs) of carcasses were analysed for post-mortem pH, protease activities (m- and alpha-calpain, calpastatin and cathepsin B + L), Warner-Bratzler shear force and sensory tenderness and juiciness. Muscles were classified into three groups, according to ultimate pH values: > 6.3, 6.3-5.8 and < 5.8. The most significant difference related to high pH was a higher activity of m-calpain at 7th day post mortem. It was also found that meat showing the highest pH was significantly more tender and juicy. Sensory tenderness was highly correlated with activity of m-calpain at 7th day post mortem (r = 0.776) and with ultimate pH (r = 0.708). It is concluded that high ultimate pH induced by stress significantly increases m-calpain activity, and this results in a greatly enhanced tenderisation of beef meat. PMID- 22061304 TI - Meat quality traits in the emu (Dromaius novaehollandiae) as affected by muscle type and animal age. AB - Meat quality traits were determined in the major muscles of the emu (Dromaius novaehollandiae) at different slaughter ages (6, 10, 14, 17 or >=20 months). A mean ultimate pH value of 5.5 was reached within around 3 h post mortem, but this value was 6.1 in animals that had suffered a preslaughter stress (transportation and fasting). The collagen and pigment contents varied widely among the muscles. The protein and pigment contents increased with animal age, but this effect was perceptible only between 6 and 14 months. The other chemical constituents were little affected by muscle type or animal age. The intense red colour of emu meat, due to a high pigment content, was very sensitive to oxidation, thus limiting the storage of fresh meat under aerobic conditions to short periods of time. Despite a rapid post-mortem tenderization (<=24 h), the residual myofibrillar strength obtained after extended ageing remained intermediate between those reported for chicken and beef. The tenderness of meat, cooked to 60 degrees C, differed between muscles and decreased with increasing age, thus reflecting the changes occuring in the concentration and in the heat stability of the intramuscular connective tissue. PMID- 22061305 TI - Sodium lactate and protective culture effects on quality characteristics and shelf-life of low-fat frankfurters produced with olive oil. AB - Low-fat frankfurters (9% fat, 13% protein) were produced with olive oil and four levels of sodium lactate (0, 1, 2, 3%). The level of sodium lactate affected (p < 0.05) moisture and ash content, processing yield, skin strength and saltiness of low-fat frankfurters. Sodium lactate at 2% level appeared to be more beneficial for the production of low-fat frankfurters with olive oil. It had the highest score for flavour intensity and did not negatively affect skin strength, lextural and sensory properties or the colour of frankfurters. Low-fat frankfurters (9% fat, 13% protein) with olive oil, produced with 0% and 2% sodium lactate (SL) and protective culture (PC) and stored under vacuum at 4 degrees C, were compared with high-fat frankfurters (27% all animal fat, 11% protein). Low-fat frankfurters with olive oil had higher (p < 0.05) moisture and lower (p < 0.05) brine concentration than high-fat frankfurters. PC extended shelf-life of low-fat frankfurters with olive oil from 3 to 4 weeks. 2% SL kept the pH of frankfurters almost constant and extended shelf-life up to 6 weeks compared with 3 and 4 weeks shelf-life for low-fat and high-fat control frankfurters, respectively. PMID- 22061306 TI - The relationship between early post-mortem pH and the tenderisation of beef muscles. AB - The rate of early post-mortem pH fall in bovine muscle was studied to determine its influence on the rate and extent of the tenderisation process. The pH of M. longissimus dorsi (LD) and M. semimembranosus (SM) muscles of Hereford cross Friesian heifers (n = 127) was taken up to 24 h post mortem. Twenty-four LD and 24 SM muscles were selected according to their rate of pH fall; slow (n = 8), intermediate (n = 8) and fast (n = 8) and were sampled at 2, 7 and 14 days post mortem for sensory, mechanical, physicochemical and biochemical analysis. Fast glycolysing LD muscles were rated more tender in sensory analysis and texture assessment whereas slow glycolysing muscles were considered significantly tougher (p < 0.001). Fast glycolysing LD had a significantly lower shear force (p < 0.001) at each stage of ageing. Slow glycolysing LD and SM had the highest shear force values. No significant difference was found in intramuscular fat or moisture content between the groups. Slow glycolysing LD muscles had shorter sarcomere lengths at 2 days post mortem. SDS-PAGE electrophoresis patterns showed increased proteolysis, such as the earlier appearance of the 30 kDa fragment, which is believed to be a good indicator of tenderness, in fast glycolysing muscle. These results suggest that the rate of post-mortem pH fall plays an important role in proteolysis and tenderisation. PMID- 22061307 TI - Influence of lairage environmental conditions and resting time on meat quality in pigs. AB - This study investigated the influence of lairage environmental conditions and resting time on pig carcasses and meat quality. The experimental material consisted of 1001 cross Pietrain-Duroc-Hampshire * Belgium-LR-LW pigs, held in lairage for either ~30 min (direct slaughter) or between 2-3 h under 12 degrees C/90% relative humidity (RH), 20 degrees C/80% or 90% RH and 35 degrees C/50% or 85% RH. Prior to arrival at the lairage plant they were transported for about 45-60 min and subjected to a fasting period of 36 h before loading. Unloading operation and the driving of pigs to the point of stunning were carried out according to the practices used in the plant (sticks and electrical goads were used). Batches of 20-30 mixed pigs were used in each trial, held at a stocking density of approximately 0.55 m(2)/pig (~100 Kg live weight). Lairage environmental conditions (LC), significantly affected almost all measurements, but not pH(1), in Semi-membranosus (SM) and Longissimus dorsi (LD) muscles and the carcass damage score. The influence of resting time (RT) was basically exerted on pH(u), deep ham temperature and in pH(1), of SM, the internal muscle reflectance being mostly unaffected. There were also significant batch (B) effects in a large range of parameters. Factors greatly interacted their influence on carcass and meat quality, denoting LC * B, LC * RT * B and LC * RT the most significant effects. RT * B only showed two low significant interactions for rigor value and pH(1), in SM, suggesting that, conversely to the lairage environmental conditions the influence of resting time is practically unaffected by the day of slaughter. The increase of lairage temperature decreased the frequency of normal carcasses, followed by an expressive higher incidence of PSE status. The influence of lairage relative humidity on the PSE/DFD muscle incidence depended on the associated temperature, but the most important detrimental effects were noticed in experiments carried out at 35 degrees C. In respect to lairage resting time, the influence on meat quality is strictly related to environmental conditions, mainly the temperature. Nevertheless, and excepting the assays at 35 degrees C/85% RH, direct slaughter of pigs (= 30 min in pens) generally produced less carcasses of normal quality than resting periods up to 2-3 h. PMID- 22061309 TI - Corrigendum. PMID- 22061308 TI - Influence of finishing diet on fatty acid profiles of intramuscular lipids, triglycerides and phospholipids in muscles of the Iberian pig. AB - Thirty Iberian * Duroc pigs allotted in groups of ten animals were fed in three traditional different management systems ('Montanera' (MO), fed on acorns; 'Recebo' (RE), fed on acorns and a commercial diet; and 'Cebo' (CE), fed on a commercial diet). Masseter muscle was obtained to evaluate the influence of management system on fatty acid (FA) composition of lean. The FA composition of the intramuscular total lipids, triglyceride (TG) and phospholipid (PL) fractions was evaluated. Muscle from MO pigs had greater quantities of monounsaturated fatty acids (MUFA) in the total lipids, triglyceride and phospholipid fractions than the other feedings. The percentage of saturated fatty acids (SFA) of i.m. total lipids and TGs increased (P < .05) with duration of feeding on RE and CE, from 35.13-35.10% in MO pigs to 37.47-37.84% in RE pigs and 39.98-41.11% in CE pigs. PLs from RE and CE pigs contained more C(18:2) and C(20:4) and less C(18:1) than MO pigs. PMID- 22061310 TI - A systematic review on the effectiveness of slowly-absorbable versus non absorbable sutures for abdominal fascial closure following laparotomy. AB - OBJECTIVE: To systematically analyse the effectiveness of delayed-absorbable (Polydioxanone; PDS) versus non-absorbable (Polypropylene; Prolene, and Nylon) for abdominal fascial closure in patients undergoing laparotomy. METHODS: Randomised trials evaluating PDS versus Prolene/Nylon for abdominal fascial closure were selected and analysed by using the statistical tool RevMan where summative data was expressed as odds ratio (OR). RESULTS: Eight randomised trials encompassing 4261 patients undergoing laparotomy closure with either PDS or Prolene/Nylon were retrieved. There was no statistically significant heterogeneity among trials. In the fixed effect model PDS was comparable to Prolene/Nylon in terms of risk of incisional hernia (OR, 1.10; 95% CI, 0.87, 1.37; z = 0.79; p = 0.43), wound dehiscence (OR, 1.04; 95% CI, 0.67, 1.62; z = 0.19; p = 0.85), peri-operative complications (OR, 0.94; 95% CI, 0.66, 1.33; z = 0.37; p = 0.71), suture sinus formation (OR, 0.58; 95% CI, 0.33, 1.04; z = 1.84; p = 0.07) and surgical site infection (OR, 0.98; 95% CI, 0.68, 1.39; z = 0.14; p = 0.89). Subgroup analysis separately comparing Prolene and Nylon with PDS supported same outcome. CONCLUSION: PDS and Prolene/Nylon are equally effective for the closure of abdominal fascia following laparotomy. Given that there are no significant differences between two suture materials, further studies may be conducted to evaluate their cost-effectiveness and measurement of health-related quality of life instead of analysing their effectiveness in laparotomy closure. PMID- 22061311 TI - Sepsis, thrombosis and organ dysfunction. AB - Sepsis is often associated with haemostatic changes ranging from subclinical activation of blood coagulation (hypercoagulability), which may contribute to localized venous thromboembolism, to acute disseminated intravascular coagulation (DIC), characterized by widespread microvascular thrombosis and subsequent consumption of platelets and coagulation proteins, eventually causing bleeding manifestations. The key event underlying this life-threatening complication is the overwhelming inflammatory host response to the infectious agent leading to the overexpression of inflammatory mediators. The latter, along with the micro organism and its derivatives are now believed to drive the major changes responsible for massive thrombin formation and fibrin deposition, namely 1) the aberrant expression of the TF by different cells (especially monocytes macrophages), 2) the impairment of physiological anticoagulant pathways, orchestrated mainly by dysfunctional endothelial cells (ECs) and 3) the suppression of fibrinolysis due to overproduction of plasminogen activator inhibitor-1 (PAI-1) by ECs and likely also to thrombin-mediated activation of thrombin-activatable fibrinolysis inhibitor (TAFI). The ensuing microvascular thrombosis and ischemia are thought to contribute to tissue injury and multiple organ dysfunction syndrome (MODS). Recent evidence indicates that extracellular nuclear materials released from activated and especially apoptotic or necrotic cells, e.g. High Mobility Group Box-1 (HMGB-1) and histones, are endowed with cell toxicity, proinflammatory and clot-promoting properties and thus, during sepsis, they may represent late mediators that propagate further inflammation, coagulation, cell death and MODS. These insights into the pathogenesis of DIC and MODS may have implications for the development of new therapeutic agents potentially useful for the management of severe sepsis. PMID- 22061312 TI - Influence of feeding vitamin D(3) and aging on the tenderness of four lamb muscles. AB - In Trial 1, rams (n=26) were fed different levels (0, 250,000, 500,000 or 750,000 IU) of vitamin D(3) for 4 days to determine the most effective dose to increase blood calcium concentrations. Trial 2 consisted of feeding feedlot lambs (n=40) different levels (0 or 750,000 IU) of vitamin D(3) for 14 days to determine if vitamin D(3) could improve the tenderness of lamb muscles. Lambs were slaughtered and the M. longissimus lumborum, M. biceps femoris, M. semitendinosus, and M. semimembranosus were removed after chilling, cut into chops, and assigned to an aging period (5, 10 or 15 days) for Warner-Bratzler shear force (WBS) determination. In Trial 1, feed intake and weight gain were lower for rams supplemented with 500,000 IU of vitamin D(3) compared to all other groups. Blood calcium concentrations were not different between groups, although the 750,000 IU group tended (P<0.10) to have higher blood calcium concentrations on day 5 of the trial compared to controls. In Trial 2, blood calcium concentrations were not different between the treated and control groups, however, treated lambs had higher (P<0.01) calcium concentrations in both the liver and kidneys. Control chops from the M. longissimus lumborum had lower (P<0.05) WBS values than chops from vitamin D(3) fed lambs, but no other muscles were affected by vitamin D(3) feeding. An interaction between treatment and aging was observed for the M. biceps femoris, with chops from vitamin D(3) fed lambs having lower WBS values at 5 days aging, but chops from control lambs having lower WBS values at 15 days aging. WBS values decreased for the M. longissimus lumborum, M. semitendinosus, and M. semimembranosus with increasing aging time. Vitamin D(3) supplementation was not an effective means of improving the tenderness characteristics of lamb muscles. PMID- 22061313 TI - A note on the total and heme iron contents of ready-to-eat doner kebabs. AB - Total and heme iron contents of ready-to-eat beef and chicken doners collected from restaurants were determined. Total and heme iron contents of beef and chicken doners were 36.70+/-9.85-15.98+/-2.86 and 14.27+/-4.43-4.49+/-1.95 MUg/g, respectively. The percent heme iron contents in beef and chicken doners were 46.06% and 34.36%, respectively. PMID- 22061314 TI - Effects of feeding intensity and time on feed on performance, carcass characteristics and meat quality of Simmental bulls. AB - Seventy two Simmental bulls, weighing 489 kg and approximately 15 months old fed extensively or intensively on maize silage and concentrate mixture for 100 or 138 days, were divided into four groups to assess the effect of time on feed and feeding intensity on the performance, carcass and meat quality traits. Bulls intensively fed for 138 days before slaughter had higher final body weight (673.7 kg) compared with the other three groups (610.6 kg, as overall mean). Intensive feeding significantly increased the average daily gain (1371 g/day) and improved the feed efficiency (6.95 kg DM/kg gain) compared with extensive feeding (943 g/day and 7.97 kg DM/kg gain). No significant differences were detected by time on feed. Hot carcass and kidney fat weights were significantly higher for intensively fed bulls compared with extensive ones. Dressing percentage significantly increased for 138 day groups compared with 100 day groups. Carcass conformation and fatness scores significantly improved by intensive feeding. L and b(*) values were not affected by time on feed or feeding intensity. Slaughtering after 138 days on feed significantly elevated the meat redness value (a(*)). Intensive feeding significantly decreased moisture and increased fat content of the longissimus dorsi muscle. Shear force, collagen content, juiciness, flavour and sarcomere length did not differ by time on feed or feeding intensity, while inconsistent effects were observed on tenderness and solubility of collagen. PMID- 22061315 TI - Moisture diffusivity in the lean tissue of dry-cured ham at different process times. AB - The aim of this study was to determine the effective moisture diffusivity coefficient (D(e)) during dry-cured ham processing in two muscles, an internal one (Biceps femoris, BF) and an external one (Semimembranosus, SM), at different temperatures. Two adjacent samples, which included both SM and BF muscles, were selected after salting (PS), after resting (PR), after 4 months of drying (D1) and at the end of the process (D2). One was used to determine the initial profiles of moisture and NaCl/moisture and the other to determine D(e) at different temperatures (1 and 5 degrees C in PS; 5 and 12 degrees C in PR; 12, 19 and 26 degrees C in D1; 19 and 33 degrees C in D2). D(e) was higher in the muscle with the higher moisture content (BF) except in PS and PR, where a gradient of NaCl/moisture ratio was observed in SM muscle. There was a positive effect of temperature on D(e), but it decreased during processing of the dry-cured ham. A simple diffusive model, with a unique and constant moisture diffusivity coefficient or with a coefficient depending only on temperature, does not explain the whole drying process correctly. The effects of moisture content and the gradient of NaCl/moisture ratio on D(e) have to be considered. PMID- 22061316 TI - Histidine dipeptides HPLC-based test for the detection of mammalian origin proteins in feeds for ruminants. AB - The present work is focused on the use of the relative amounts of carnosine and anserine for detecting the presence of proteins of mammalian origin in feeds for ruminants. The methodology is cheap and simple and may serve for the rapid screening of feeds. Animal protein additions to feeds as low as 0.5% can be easily detected based on the cation exchange HPLC determination of the carnosine and/or anserine dipeptides. Furthermore, the molar ratio of these dipeptides was found to be characteristic of the animal species and could be used to discriminate between mammalian and non-mammalian species eventually added to feeds. Feeds having carnosine/anserine molar ratios higher than 0.3 were strongly suspected of containing banned mammalian proteins. Those suspicious feeds might be later confirmed by more specific techniques. The exact source of feeds containing mixtures of animal proteins from different species could not be identified by this method even though the method was able to detect its mammalian origin. PMID- 22061317 TI - A rapid method based on front-face fluorescence spectroscopy for the monitoring of the texture of meat emulsions and frankfurters. AB - In order to investigate the potential of fluorescence spectroscopy to characterise meat emulsions and frankfurters, a split-plot design comprising three factors at three levels each, i.e. fat/lean ratios (0.25, 0.7 and 1.5), chopping speed (1000, 2000 and 3000 rpm) and chopping time (1, 3 and 7 min), was considered. Principal component analysis and hierarchical ascendant clustering performed on the texture attributes and L(*)a(*)b(*) value data sets for the batters and frankfurters showed that a limited number of clusters can be discriminated, mainly according to the chopping conditions. From the fluorescence spectra of batters and frankfurters, the similarity maps defined by principal components 1 and 2 allowed clear discrimination between formulations with a high fat content from those of low fat content, whereas formulations with an intermediate fat content overlapped. Canonical correlation analysis (CCA) showed strong correlations between the batter texture attributes and the batter fluorescence spectra since the first pairs of canonical variates exhibited squared correlation coefficients of 0.88. Moreover, it was shown by CCA that batter fluorescence spectra and frankfurter texture-attributes were highly correlated (r(2)=0.91) for the first canonical variates suggesting that it may be possible to predict the texture of a frankfurter from a fluorescence spectrum recorded on the batter. PMID- 22061318 TI - Effects of carbon dioxide on yield, texture and microstructure of cooked ground beef. AB - The objective of the study was to find the effects of CO(2) gas on cooking loss, instrumental hardness and microstructural changes of ground beef heated to 70-83 degrees C. In two experiments, ground beef was stored for 4 days in 60% CO(2)/39.6% N(2)/0.4% CO and vacuum (1), or in 100% CO(2), 50% CO(2)/50% N(2), 20% CO(2)/80% N(2), 100% N(2) and vacuum (2). In an additional experiment, slices of beef semimembransosus muscles were stored for 10 days in 100% CO(2), 100% N(2) and vacuum. Cooking loss of ground beef patties was higher of all CO(2) treatments than non-CO(2) treatments (p<0.05). Storage of raw ground beef in CO(2) caused a concentration dependent decrease in raw meat pH of up to 0.12 units in 100% CO(2). In the beef slices, small CO(2) related fissures and pores were formed in the cooked meat. These changes in pH and microstructure probably contributed to the elevated cooking loss. The hardness of cooked ground beef was not affected by CO(2) exposure (p>0.05). Because CO(2) in concentrations of 20 100% is commonly used in industrial packaging processes for retail meat and meat trimmings, a reduction in cooking yield of 1-3% may have sensory and economic implications. PMID- 22061319 TI - Effect of storage and packaging on fatty acid composition and oxidation in dry fermented sausages made with added olive oil and antioxidants. AB - Dry fermented sausages produced by a partial substitution of pork backfat with pre-emulsified olive oil were manufactured and stored (2 and 5 months) using different packaging conditions (aerobic/vacuum piece/vacuum slices) in order to evaluate the intensity of the oxidation process. Also the effect of the addition of butylhydroxytoluene (BHT) and butylhydroxyanisole (BHA) to one of the modified batches was studied. Addition of olive oil, especially with antioxidants, was more effective than using vacuum storing methods in avoiding lipid oxidation during storage. After 5 months of storage at 4 degrees C, the combination of the increase in oleic acid and the preservation of PUFA by the antioxidant activity of the olive oil emulsion and antioxidants (when added), lead to better MUFA+PUFA/SFA ratios in olive oil containing sausages (1.90-1.98 g/100 g fatty acids) and particularly in antioxidants containing sausages (2.02-2.16 g/100 g) than in control ones (1.72 g/100 g). Vacuum packaging of the piece was the best method to minimise formation of lipid oxidation volatile compounds. PMID- 22061320 TI - Effects of rye bran addition on fatty acid composition and quality characteristics of low-fat meatballs. AB - Rye bran was used as a fat substitute in the production of meatballs. The effect of rye bran addition on the fatty acid composition, trans fatty acids, total fat, some physico-chemical and sensory properties of the samples was studied. Meatballs were produced with four different formulations including 5%, 10%, 15% and 20% rye bran addition. Control samples were formulated with 10% fat addition. Meatballs containing rye bran had lower concentrations of total fat and total trans fatty acids than the control samples. Meatballs made with addition of 20% rye bran had the highest protein, ash contents, L value (lightness), b value (yellowness), and the lowest moisture, salt content and weight losses and a value (redness). There was a significant difference among the meatball samples in respect to sensory properties and 5%, 10% rye bran added meatballs and control samples had high acceptability. PMID- 22061321 TI - The relationship between postmortem urinary catecholamines, meat ultimate pH, and shear force in bulls and cows. AB - We investigated the relationship between stress responsiveness and meat quality in cattle. The cattle were 16-19-month-old Mixed (n=37, 303 kg) or Non-mixed (n=23, 279 kg) Friesian bulls and Friesian cull cows (1.5-7 years) that were classified Unfinished (n=133, 195 kg) or Finished for 3 months (n=34, 252 kg). A portion of m. longissimus lumborum (LL) muscle was obtained from consecutive animals for a single days slaughter of 227 cattle processed through a hot boning plant. Catecholamines were obtained from bladder urine. Ultimate pH, lactate, glycogen, glycolytic potential and representative sarcomere lengths were determined from 20-h muscle samples. Shear force measurements were from meat aged at 15 degrees C for 20 and 90 h. Urinary noradrenaline was similar between Mixed (14.86 ng/MUmol creatinine) and Non-mixed bulls (14.07 ng/MUmol creatinine) and Finished cows (15.24 ng/MUmol creatinine) and elevated in the Unfinished cows (22.28 ng/MUmol creatinine). Urinary adrenaline was higher in Mixed bulls (9.5 ng/MUmol creatinine) than Non-mixed bulls (5.7 ng/MUmol creatinine) and higher in both Unfinished cows (16.67 ng/MUmol creatinine) and Finished cows (14.19 ng/MUmol creatinine). For bulls that are growing well on-farm, with a only short period of fasting prior to slaughter, pH(u) is a good predictor of meat tenderness. In this situation, stressors that lower muscle glycogen pre-slaughter can have a significant effect on meat shear force, and individual animals with elevated urinary adrenaline were the most susceptible. However, in the case of cows, adrenaline responses are not necessarily associated with glycogen depletion and pH(u) is less affected than for bulls. Furthermore, the ability of meat to tenderise fully, related to reduced proteolytic turnover, is reduced in nutritionally compromised animals such as the Unfinished cows. PMID- 22061322 TI - The effects of finishing diet and postmortem ageing on the eating quality of the M. longissimus thoracis of electrically stimulated Brahman steer carcasses. AB - Beef from cattle finished on grass will be of similar quality to that from cattle finished on grain when their carcasses are processed using best practice protocols. To test this hypothesis, carcasses of twenty Brahman steers, finished to 400 kg live weight on either Buffel grass pasture (n=10) or grain (n=10), were electrically stimulated with 400 V for 50 s 45 min postmortem, and their beef quality assessed 1 and 14 days postmortem. Hot weight, rump subcutaneous fat thickness and animal rate of growth in the 205 days preceding slaughter were recorded for each carcass as potential influences on beef quality. Quality of the M. longissimus thoracis (LT) at 1 and 14 days postmortem was evaluated using peak Warner-Bratzler shear force, compression, pH, cooking loss and taste panel acceptability, as well as by moisture and crude fat contents measured at 1 day postmortem. Results showed that steers finished on pasture grew the slowest and had the least subcutaneous fat at the same carcass weight. LT from carcasses of steers finished on pasture also had the shortest mean sarcomere lengths, suggesting these muscles may have been cold-affected, but there was no effect of diet on peak shear force. LT from carcasses of steers finished on pasture had the highest mean compression value, possibly because of increased collagen cross linking associated with slow growth or increased exercise. Ageing significantly decreased LT peak shear force and compression values and increased cooking loss, L (*), a (*) and b (*) values. Taste panellists rated the aged, grass-finished beef the most tender and the best quality; however, the taste panel in this study may have favoured LT from grass-finished steers because it was significantly juicier than LT from the grain-finished steer carcasses. These results indicated that carcass composition and processing conditions interact to exert a greater effect on LT toughness and sensory acceptability than finishing diet. Ageing LT from steers finished on grass improved its colour, and thus may enhance its consumer acceptability. PMID- 22061323 TI - Video image analysis in the Australian meat industry - precision and accuracy of predicting lean meat yield in lamb carcasses. AB - A wide selection of lamb types of mixed sex (ewes and wethers) were slaughtered at a commercial abattoir and during this process images of 360 carcasses were obtained online using the VIAScan(r) system developed by Meat and Livestock Australia. Soft tissue depth at the GR site (thickness of tissue over the 12th rib 110 mm from the midline) was measured by an abattoir employee using the AUS MEAT sheep probe (PGR). Another measure of this thickness was taken in the chiller using a GR knife (NGR). Each carcass was subsequently broken down to a range of trimmed boneless retail cuts and the lean meat yield determined. The current industry model for predicting meat yield uses hot carcass weight (HCW) and tissue depth at the GR site. A low level of accuracy and precision was found when HCW and PGR were used to predict lean meat yield (R(2)=0.19, r.s.d.=2.80%), which could be improved markedly when PGR was replaced by NGR (R(2)=0.41, r.s.d.=2.39%). If the GR measures were replaced by 8 VIAScan(r) measures then greater prediction accuracy could be achieved (R(2)=0.52, r.s.d.=2.17%). A similar result was achieved when the model was based on principal components (PCs) computed from the 8 VIAScan(r) measures (R(2)=0.52, r.s.d.=2.17%). The use of PCs also improved the stability of the model compared to a regression model based on HCW and NGR. The transportability of the models was tested by randomly dividing the data set and comparing coefficients and the level of accuracy and precision. Those models based on PCs were superior to those based on regression. It is demonstrated that with the appropriate modeling the VIAScan(r) system offers a workable method for predicting lean meat yield automatically. PMID- 22061324 TI - Development of breed identification markers derived from AFLP in beef cattle. AB - In the meat industry, correct breed information in food labeling is required to assure meat quality. Genetic markers provide corroborating evidence to identify breed. This paper describes the development of DNA markers to discriminate between Japanese Black and F1 (Japanese Black*Holstein) breeds. Amplified fragment length polymorphism method was employed to detect candidate markers absent in Japanese Black but present in Holstein. The 500 primer combinations yielded six selected markers that were converted into single nucleotide polymorphisms markers for high-throughput genotyping. The allele frequencies in both breeds were investigated for discrimination ability using PCR-RFLP. The probability of identifying F1 was 0.882 and probability of misjudgment was 0.0198. The markers could be useful for discriminating between Japanese Black and F1 and would contribute to the elimination of falsified breed labeling of meat. PMID- 22061325 TI - Quantification of fresh meat peptides by SDS-PAGE in relation to ageing time and taste intensity. AB - The extraction and quantification of fresh meat peptides in the molecular weight (MW) range between 3 and 17 kDalton (kDa) was examined, as well as their evolution during post-mortem ageing and their relation to taste intensity. Using a Tricine-sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) method, quantification of fresh meat peptides in this MW range was possible. Correlation coefficients higher than 0.98 were found between the absolute amounts of peptides loaded on the gel and the measured amounts expressed as cytochrome c equivalents. In contrast to the extraction in the presence of SDS, extraction with 0.1 N HCl, 3% HClO(4) and 0.9% NaCl only partially recovered peptides present in fresh meat samples in both the 3-10 and 10-17 kDa MW range. A substantial increase in peptide concentration in the 3-17 kDa MW range with time post-mortem in both pork and beef fresh muscle samples was found. For grilled beef longissimus lumborum and semimembranosus samples of different origin and ripening times, both the concentration of the peptides in the 3-10 kDa MW range and the intramuscular fat content were significantly related with taste panel intensity scores, while the correlation with the amount of peptides in the 10-17 kDa MW range was not significant. PMID- 22061326 TI - Fatty acid profile, cholesterol content and tenderness of meat from Podolian young bulls. AB - Fatty acid profile, cholesterol content and sensory properties of meat from Podolian young bulls were evaluated. The percentage of saturated fatty acids was higher for LD and lower for SM and ST muscles (P<0.001). Oleic and stearic fatty acids constituted more than 50% of the total fatty acids in all muscles studied. The meat produced by Podolian young bulls showed a favourable percentage content of polyunsaturated fatty acids and a beneficial ratio P/S. Conversely, the ratio n-6/n-3 exceeded the recommended value in the human diet. Changing the time of ageing from 8 to 15 days produced an increment of MDA (P<0.01). The differences in MDA content observed between meat samples aged 8 and 15 days were still detectable after 4 and 8 months of frozen storage. The extension of the ageing period from 8 to 15 days produced an increase in tenderness (P<0.05) and flavour intensity (P<0.01). PMID- 22061327 TI - Meat quality characteristics in different lines of Iberian pigs. AB - Physico-chemical parameters involved in technological meat quality for dry cured processing of four different lines (Entrepelado, Lampino, Retinto and Torbiscal) of Iberian pigs were studied in the Masseter (MS) and Longissimus dorsi (LD) muscles. The line of Iberian pig significantly affected intramuscular fat content of MS muscle, animals from the Torbiscal line showing lower values. Proportions of several fatty acids of total lipids and polar lipids from the MS muscle were also affected. However, fatty acid composition and total lipids, neutral lipids and polar lipids of LD muscle and neutral lipids of MS muscle were scarcely affected. Lipid oxidation was also unaffected by Iberian pig line, but instrumental colour parameters of MS muscle showed significant variations. PMID- 22061328 TI - Selection of Lactobacillus strains from fermented sausages for their potential use as probiotics. AB - A rapid screening method was used to isolate potentially probiotic Lactobacillus strains from fermented sausages after enrichment in MRS broth at pH 2.5 followed by bile salt stressing (1% bile salts w/v). One hundred and fifty acid- and bile resistant strains were selected, avoiding preliminary and time-consuming isolation steps. Strains were further characterized for survival at pH 2.5 for 3 h in phosphate-buffered saline and for growth in the presence of 0.3% bile salts with and without pre-exposure at low pH. Twenty-eight strains showed a survival >80% at pH 2.5 for 3 h; moreover, most of the strains were able to grow in the presence of 0.3% bile salts. Low pH and bile resistance was shown to be dependent on both the species, identified by phenotypic and molecular methods, and the strain tested. This is the first report on the direct selection of potentially probiotic lactobacilli from dry fermented sausages. Technologically interesting strains may be used in the future as probiotic starter cultures for novel fermented sausage manufacture. PMID- 22061329 TI - The effect of dietary supplementation of vitamins C and E on the alpha-tocopherol content of muscles, liver and kidney, on the stability of lipids, and on certain meat quality parameters of the longissimus dorsi of rabbits. AB - The trial was carried out to investigate the effects of adding to the diet of rabbits vitamin E (40; 300; 500 ppm) and C (0; 500 ppm), on vitamin E deposition in the muscles and organs, on the oxidative stability of muscular lipids, and on various meat quality characteristics. The alpha-tocopherol content in muscles and organs was roughly doubled by feeding the highest levels of vitamin E; it was also increased by giving 500 ppm of vitamin C, but only in those muscles of rabbits receiving 40 ppm of vitamin E. The alpha-tocopherol content in tissues was negatively correlated with TBARS values of the longissimus dorsi (LD) at days 6 and 8 post mortem (p.m.). Five hundred parts per million (ppm) of vitamin C increased lipid stability of the LD at both 6 and 8 days p.m., though its effect was significant only with 40 ppm of vitamin E. Moreover, 500 ppm of vitamin C resulted in the lowest L(*) and highest pH values at all p.m. times, when the dietary vitamin E was equal to 40 ppm, and in the highest L(*) and lowest pH values when the vitamin E was equal to 300 ppm. Conversely, weight losses of the LD were the lowest, at days 6 and 8 p.m., in the group fed the highest levels of both vitamins. PMID- 22061330 TI - Perimysium thickness as an indicator of beef tenderness. AB - Eight bovine muscles were evaluated to determine if perimysium thickness (PT) differed among muscles and carcasses and was affected by electrical stimulation (ES). In addition, the effect of PT on Warner-Bratzler shear (WBS) of steaks divided into tenderness groups was evaluated. Muscle and carcass affected (P<0.05) PT, but PT was not significantly affected by ES. Correlation coefficients revealed that PT would be a poor indicator of WBS when used alone (r=0.13). When analyzed within electrical stimulation treatment, PT was correlated (P<0.05) to WBS of NES (r=0.21) carcasses and not significantly related to WBS of ES carcasses. Within tenderness groups, PT accounted for 4.5%, 9.5%, 20.0%, and 4.0% of the variation in WBS force at 3, 7, 14, and 21 d, respectively. These results indicate that PT can be used in conjunction with other myofibrillar components of tenderness to account for some variation in WBS values of cooked beef steaks. PMID- 22061331 TI - Effects of modified corn gluten meal on quality characteristics of a model emulsified meat product. AB - The objective of this study was to evaluate the effects of soy protein isolate (SPI), three forms of native corn gluten meal on sensory, color and textural characteristics of an emulsified meat product. The meals included native corn gluten meal (CGM) that had been ph-adjusted from 4.4 to 6.6 and particle size reduced to either ~38 (MC38) or ~7 MUm (MC7). When judged by a trained sensory panel, all CGM-based substances contributed the same degree of CGM off-odor intensity, but significantly lowered pork odor intensity when compared to SPI containing products and controls. SPI and all CGM-based substances increased grain-like odor. Visual off-color was apparent in all meat products containing CGM-based substances. Instrumental color evaluation indicated that products containing CGM-based substances were lighter, more yellow colored than control and SPI-containing products. However, sensory denseness, springiness and cohesiveness, and texture profile analyses of meat products were not affected. PMID- 22061332 TI - Production of biogenic amines in "Salamini italiani alla cacciatora PDO". AB - Various fermented and seasoned foods such as cheese, sauerkraut, wine, beer and meat products may contain biogenic amines. The aim of this paper was to describe the presence of some biogenic amines (histamine, tyramine, tryptamine, 2 phenylethylamine) in "Salamini italiani alla cacciatora PDO", a typical fermented ripened dry sausage widely consumed in Italy. Total level of biogenic amines in commercial samples ranged from 71 to 586 mg kg(-1). The amine recovered in higher concentrations was tyramine (372 mg kg(-1)) followed by histamine (165 mg kg( 1)). The second aim of this work was the quality control of the production in order to determine the parameters influencing the presence of biogenic amines in ripened salami. Sausages sampled for analysis during production, manipulation and ripening showed the presence of tyramine (64.4 mg kg(-1)) only after 15 days of fermentation. All investigated biogenic amines were detected in "Salamini" after 21 days of fermentation. We suggest the control of biogenic as important tool to establish the better condition of preservation of "Salamini italiani alla cacciatore PDO" during their shelf-life. PMID- 22061333 TI - The effect of age on distribution of skatole and indole levels in entire male pigs in four breeds: Yorkshire, Landrace, Hampshire and Duroc. AB - High skatole and to a lesser degree indole levels in some entire male pigs result in occurrence of off-flavor in meat, called boar taint. In this study, plasma samples from 117 Yorkshire, 134 Landrace, 184 Hampshire and 75 Duroc entire male pigs collected at different ages were analyzed for skatole and slightly fewer samples for indole concentrations. For each breed, a distinct age-related distribution of plasma skatole levels was observed. Skatole levels were increased at approximately 180-200 days of age, reaching very high levels is some individuals. Afterwards, the levels decreased; in Yorkshire and Landrace at approximately 240-260 and in Hampshire and Duroc at 310-360 days of age. The decrease of skatole levels was also observed in samples collected from 15 Landrace boars at two different ages: 16.8 MUg/L (SD=17.36) vs. 5.9 MUg/L (SD=3.48, p=0.016) in samples taken at the mean age of 210 and 314 days, respectively. Indole levels showed similar age- and breed-related variations to skatole. At the time of increased skatole concentrations (age from 180 to 360 days, depending on breed) 25.5% of Yorkshire, 31.6% of Landrace, 20.3% of Hampshire and 61.1% of Duroc entire male pigs had skatole levels above 12.6 MUg/L of plasma, which corresponds to the threshold level of 0.20 MUg/g of fat that is used for selecting tainted carcasses. The results indicate that increased levels of skatole in entire male pigs are related to puberty and taking skatole measurements at that age could be advantageous when considering genetic selection to reduce boar taint level in entire male pigs. Breed differences should be also taken into account. PMID- 22061334 TI - Composition and sensory evaluation of lamb carcasses used for the traditional Mexican lamb dish, "barbacoa". AB - The objective of this study was to determine the differences in carcass characteristics and sensory attributes of "barbacoa" (a traditional Mexican lamb dish), both of imported (New Zealand) and domestic lambs in Mexico. A total of 28 carcasses from Pelibuey, Pelibuey*Suffolk and imported lambs were used. Carcass composition was determined by dissection of primal cuts from the left half of each carcass. The "barbacoa" from each ovine group was prepared separately in order to perform a consumer sensory evaluation for aroma, taste and tenderness. Results showed that imported lambs had larger carcasses, greater fatness and had better conformation than national lambs. There was no difference between groups in terms of lean tissue percentage (muscle+others) or in total carcass fat. The sensory attributes of the "barbacoa" did not differ among breeds. Pelibuey lambs (rustic, prolific and adaptable to the wide variety of Mexican climates) show competitive production performance in relation to specialized breeds. PMID- 22061335 TI - The effect of dietary magnesium oxide supplementation on postmortem (31)P NMR spectroscopy parameters, rate of Ca(2+) uptake and ATPase activity of M. longissimus dorsi and meat quality of heterozygous and normal on malignant hyperthermia pigs. AB - Twenty four crossbred (Large White, White Meaty, Pietrain, Hampshire) pigs were tested by DNA probe for a mutation on the ryanodine receptor RYR1 (malignant hyperthermia-MH). An equal number of pigs heterozygote (monomutant-MON) and normal on MH (nonmutant-NON) were used in the experiment. The pigs were fed finisher feed (control group) or finisher feed supplemented with magnesium (3.6 g MgO per pig per day; MgO group) for 5 days prior to slaughter. Pigs fed the diet supplemented with MgO had higher plasma Mg concentrations. Phosphorus nuclear magnetic resonance ((31)P NMR) measurements on postmortem (15 min) muscle samples (longissimus muscle) showed the highest phosphocreatine levels in normal pigs fed MgO (P<0.05). The MgO supplementation caused increased Ca(2+) uptake and Ca(2+) ATPase activity only in normal (NON) pigs. ATPase activity was lowest (P<0.05) in heterozygote control pigs. Pigs fed MgO supplemented diet had higher pH (45 min postmortem). A significant lower pH (P<0.05) was obtained in heterozygous (MON) control pigs. Also pigs fed with MgO had lower percentage of drip losses and significant differences (P<0.05) were obtained between heterozygous (MON) pigs. The results indicate that dietary MgO supplementation can improve parameters of muscle energetic metabolism, Ca(2+) uptake and meat quality (pH, drip loss). PMID- 22061336 TI - Study on the usefulness of high-molecular-weight (HMW)-Adiponectin level check of Japanese general population upon health check: comparison of carotid ultrasonography measurement. AB - OBJECTIVE: High-molecular-weight (HMW)-adiponectin is an active and powerful predictor of atherosclerosis. Unfortunately, there is currently no reliable epidemiological reference level data available in Japan. The current ELISA method for HMW-adiponectin measurement is tedious as it requires several sample pre treatment steps. We studied the reference level of HMW-adiponectin measured by a simple, fully-automated CLEIA. DESIGN: The study subjects were 858 men and 793 women who underwent health check-ups at a Japanese Red Cross Medical Center. We investigated the relation between HMW-adiponectin and metabolic parameters, including carotid ultrasonography. RESULTS: The mean values of HMW-adiponectin were 3.11 +/- 1.99 MUg/ml in men, and 5.52 +/- 3.07 MUg/ml in women. There were significant differences (p<0.001) in relation to gender and age, where levels gradually increased with age. HMW-adiponectin was 3.18 +/- 1.45 MUg/ml in male subjects without carotid lesions, and 2.28 +/- 0.90 MUg/ml in male subjects with lesions. CONCLUSIONS: HMW-adiponectin measured by simple CLEIA could be useful for routine risk assessment. PMID- 22061337 TI - Correlation of creatinine with TSH levels in overt hypothyroidism - a requirement for monitoring of renal function in hypothyroid patients? AB - OBJECTIVE: Renal function is influenced by thyroid status. Therefore, this study was done to determine the relationship between renal function and different degrees of thyroid dysfunction. DESIGN AND METHODS: Thyroid and kidney function tests were analyzed in 47 patients with overt (TSH >= 10.0 MUIU/L) and 77 patients with subclinical hypothyroidism (TSH 6.0-9.9 MUIU/L) in a cross sectional study. These were compared with 120 age- and sex-matched euthyroid controls. RESULTS: Overt hypothyroid subjects showed significantly raised serum urea, creatinine and uric acid levels as compared to controls whereas subclinical hypothyroid patients showed significant increased levels of serum urea and creatinine levels. TSH showed significant positive correlation with creatinine and uric acid values and, fT4 had a negative correlation with uric acid in overt hypothyroidism. CONCLUSION: Hypothyroid state is associated with significant derangement in biochemical parameters of renal function. Hence the renal function should be regularly monitored in hypothyroid patients. PMID- 22061338 TI - Identification of possible biomarkers for breast cancer from free fatty acid profiles determined by GC-MS and multivariate statistical analysis. AB - OBJECTIVES: The aim was to investigate the free fatty acid (FFA) metabolic profiles and to identify biomarkers that can be used to distinguish patients with breast cancer (BC) from benign (BE) patients or healthy controls. DESIGN AND METHODS: A total of 114 subjects were divided into the following three groups: BC patients, BE patients and controls. The FFA profiles in three groups were studied by gas chromatography-mass spectrometry coupled with multivariate statistical analysis. RESULTS: Three saturated fatty acids (C14:0, C16:0 and C18:0) and three unsaturated fatty acids (C18:2, C18:3 and C20:5) in BC were significantly different than controls. Palmitic acid, stearic acid, linoleic acid and total FFA were identified as potential biomarkers distinguished BC from the other groups. CONCLUSION: The alterations of FFA could reflect underlying metabolic changes in BC patients, and this study has demonstrated that FFA biomarkers might be helpful for prevention and characterization of BC patients. PMID- 22061339 TI - Substance use in lesbian, gay, and bisexual populations: an update on empirical research and implications for treatment. AB - Historically, substance use problems were thought to be more prevalent in lesbian, gay, and bisexual (LGB) populations, and correcting skewed perceptions about substance abuse among LGB individuals is critically important. This review provides an update on empirical evidence on LGB substance use patterns and treatment outcome, with specific focus on clinical implications of findings. Compared to earlier studies, the recent research included in this review has used more sophisticated methodologies and more representative samples, and also has investigated multiple dimensions of sexual orientation in relation to substance use patterns. Findings from recent research suggest that lesbians and bisexual women are at greater risk for alcohol and drug use disorders and related problems, and that gay and bisexual men are at greater risk for illicit drug use and related problems. Several sociocultural factors have emerged as correlates of substance use patterns in LGB populations (e.g., affiliation with gay culture, HIV status), and several demographic characteristics (e.g., female, older age) do not appear to be as robust of protective factors against substance abuse for LGB individuals compared to heterosexual populations. Bisexual identity and/or behavior in particular seem to be related to increased risk for substance abuse. In terms of treatment outcome, limitations of extant research prevent conclusions about the relative impact of LGB-specific interventions, and further research that includes women and uses more equivalent comparison interventions is needed. Clinical implications of research findings are discussed for case identification, selection of treatment goals (e.g., moderation vs. abstinence), targets for intervention, and specific treatment modalities. PMID- 22061341 TI - The bacteriological quality of British beef 2. Frozen minced beef. AB - Frozen minced beef was obtained from five commercial wholesale producers, and the aerobic plate count, and counts of coliforms, Escherichia coli type 1 and Staphylococcus aureus, determined. No E. coli O157:H7 or salmonellas were detected. The results were evaluated in relation to: (1) two earlier surveys involving fresh mince purchased from retail butchers and supermarkets in the UK (Roberts et al., 1980; Hudson et al., 1986); and (2) the standards set out in Annex II of the Minced Meat Directive 94/65/EC. In respect to the latter, none of the 99 samples of mince examined was unsatisfactory. PMID- 22061340 TI - Transitions in first-year college student drinking behaviors: does pre-college drinking moderate the effects of parent- and peer-based intervention components? AB - This study used Latent Transition Analysis (LTA) to examine a stage-sequential model of alcohol use among a sample of high-risk matriculating college students (N=1,275). Measures of alcohol use were collected via web-administered surveys during the summer before entering college and followed-up during the fall semester of college. Seven indicators of alcohol use were used in the LTA models, including temporal measures of typical drinking throughout the week. The results indicated that four latent statuses characterized patterns of drinking at both times, though the proportion of students in each status changed during the transition to college: (a) nondrinkers; (b) weekend nonbingers; (c) weekend bingers; and (d) heavy drinkers. Heavy drinkers were distinguished by heavy episodic drinking (HED), and increased likelihood of drinking throughout the week, especially on Thursdays. Covariates were added to the LTA model to examine the main and interaction effects of parent- and peer-based intervention components. Results indicated that participants in the parent and peer conditions were least likely to transition to the heavy drinkers status. Results also indicated that the parent condition was most effective at preventing baseline nondrinkers from transitioning to heavy drinkers whereas the peer condition was most effective at preventing escalation of use among weekend nonbingers. The results underscore the value of considering multiple dimensions of alcohol use within a person-centered approach. Differential treatment effects were found across baseline drinking class, suggesting the benefit for tailored intervention programs to reduce high-risk drinking among college students. PMID- 22061342 TI - The bacteriological quality of British beef 3. Frozen primal joints. AB - The bacteriological status of 286 primal cuts stored frozen in intervention stores in England, Scotland and Northern Ireland for between 18 and 216 weeks was assessed in two surveys carried out during 1993 (120 cuts) and 1994 (166 cuts). Overall the aerobic plate count at 25 degrees C and the presumptive pseudomonad counts were <10(5)cm(2) on 269 (94%) and 273 (95.5%) of the cuts, respectively. Similarly the coliform and enterococcal counts were <10(3)cm(2) on 98.3% and 97.9% of the cuts, respectively. These findings suggest that the quality of dressing and butchery of the carcasses was of a generally satisfactory standard although on occasions there may have been suboptimum hygiene control during slaughter and butchery or some delay before freezing. The bacterial numbers were higher on average on the cuts obtained from the lower part of the carcass while there was a tendency for the number of aerobic spoilage organism to decrease slightly with increasing storage time. Evidence was obtained in the second survey which indicated differences between microbiological quality of meat coming from different boning plants although it was not possible to make a detailed evaluation of this point as the number of cuts available for sampling from each plant differed in each year. PMID- 22061343 TI - Histochemical characteristics in relation to meat quality properties in the Longissimus Lumborum of fast and lean growing lines of Large White pigs. AB - A selection experiment was carried out to study genetic and physiological factors influencing meat quality in lines of Large White pigs selected for lean (L) or fast (F) growth. Second and fourth generation pigs were used to determine effects on fibre type composition, fibre diameters and capillary density in the Longissimus Lumborum (LL). Significant differences in histochemical properties were found in the LL between L- and F-pigs, but only in the 4th generation. L pigs had significantly less type I and more type IIB myofibres compared to F-pigs in both sexes. In both lines lower type I and higher type IIB percentages were determined in gilts compared with boars. Significant differences in meat quality properties between L- and F-pigs were found in the LL, but only in the 4th generation. The a* values were significantly higher in F- versus L-pigs and in boars versus gilts. L* values were not significantly different between lines. However, L* values were significantly lower in 4th versus 2nd generation pigs and in boars versus gilts. In conclusion, genetic selection on lean versus fast growth induces differences in fibre type composition of the LL. These differences become visible in the 4th generation, when a certain selection effect is achieved. Fibre type composition was influenced by the gender of the animal. Meat quality showed significant differences between lines in meat colour (a* value), but only in the 4th generation. Capillary density and fibre area between L- and F lines showed minor differences, which could be explained by the differences in weight and age of the pigs of both lines. PMID- 22061344 TI - Effect of the dietary supplementation with Vitamin E on colour stability of packaged, sliced pasteurized ham. AB - The effect of dietary supplementation with vitamin E (200IU kg(-1) feed) on the colour stability of pasteurized ham was studied. Pigs were fed on control and enriched diets for the last 12 weeks before slaughter. Pasteurized ham was manufactured from the hams from 6 barrows and 6 gilts per dietary group. Half of the samples of sliced ham from control and supplemented pigs were packaged under vacuum (VAC) and half in low-oxygen modified atmosphere packs (FOG, gas mixture: CO(2)/N(2)=60/40). Half the packages were kept under constant illumination and the other half in the dark, both for 22 days at 7 degrees C. The redness component of the VAC-packaged ham prepared from vitamin E-supplemented pigs was slightly more stable than that of comparably packaged ham prepared from control pigs. The opposite was observed for the FOG-packaged products. Overall, colour changes were greater in the ham in FOG-packs than in the ham in VAC-packs. In addition, the colour of the FOG-packaged ham was clearly affected by illumination, whereas the colour of the VAC-packaged ham appeared more stable. It is concluded that dietary supplementation of pigs with vitamin E does not appear to offer significant advantages over currently used feeding regimens with regard to the quality of the ham produced. PMID- 22061345 TI - The effect of handling pre-slaughter and carcass processing rate post-slaughter on pork quality. AB - Forty-eight male crossbred (Large White-Landrace) pigs were used in a 2*2 factorial design to determine the effect of pre-slaughter handling (minimal and negative handling prior to slaughter) and the rate of carcass processing post slaughter [normal rate (45min) and delayed rate (70min) from time of exsanguination to carcass entering the chiller] on muscle glycolysis and pork quality. Pigs negatively (using an electric goad) handled at the abattoir just prior to slaughter had lower muscle glycogen concentrations in the Longissimus thoracis (LT) and the Biceps femoris (BF) at all times post-slaughter and lower lactic acid at 5, 45 and 70min post-slaughter compared to pigs minimally (no use of electric goads) handled prior to slaughter. Negative handling of pigs just prior to slaughter also resulted in pork which had higher surface exudate and a higher incidence of PSE compared with pigs minimally handled prior to slaughter. A prolonged rate of carcass processing resulted in reduced muscle glycogen in the LT and BF at all times post-slaughter. Delays in carcass processing rate also affected pork quality, as the meat was paler in comparison with pig carcasses that were processed without any delays. The results from this experiment have indicated that the use of electric goads to move pigs at the abattoir, and delays in carcass processing post-slaughter, can have a detrimental influence on ultimate pork quality. PMID- 22061346 TI - The effect of stocking density in transit on the carcass quality and welfare of slaughter pigs: 1. Carcass measurements. AB - In a trial involving 2496 pigs, the effect of transport stocking densities of 201, 241, 281 and 321kg m(-2) on carcass quality and welfare were evaluated. This range encompassed the upper level set for 100kg pigs in European Union legislation (235kg m(-2)). Four farms and two lorries were involved over 16 experimental days with an average journey time of 3hr. Stocking density had no effect on any variables measured. Source farm had a significant effect on ultimate pH, reflectance and electrical conductivity in the m. longissimus dorsi, reflectance in the m. adductor and extent of rigor mortis development in the m. semimembranosus. Overall, the measurements made produced no evidence that transport stocking density had an effect on the carcass quality or welfare of 95kg pigs on short journeys. PMID- 22061347 TI - The effect of stocking density in transit on the carcass quality and welfare of slaughter pigs: 2. Results from the analysis of blood and meat samples. AB - In a trial involving 2496 pigs, the influences on blood profile and pork quality of stocking densities ranging from 201 to 321kg m(-2) were examined. The pigs came from four different farms and were killed in 16 weekly batches. They were transported for on average 3hr and held in lairage for 1hr. Higher stocking densities resulted in more physical stress to the pigs based on the activity of the enzyme CPK in the blood. Stocking density did not apparently affect psychological stress and high densities did not result in dehydration. The colour, water holding capacity and instrumentally-determined texture of the pork from the carcasses of the pigs were not affected by stocking density. The experimental design and precision of the measurements were sufficient to detect numerous differences in blood profile and pork quality between pigs from the four source farms. These differences probably related to different degrees of stress susceptibility. The results suggest that the highest stocking density examined (321kg m(-2)) is unacceptable for the transport of pigs. The second highest density (281kg m(-2)) produced relatively little evidence of an adverse effect on the welfare of pigs. It may be scientifically acceptable for short journeys (<=3hr) but not for longer ones where pigs need more space to lie down. PMID- 22061348 TI - Influences of the method of housing bulls on their body composition and muscle fibre types. AB - The influence of the type of housing (loose or tying-type) was studied in relation to body composition and muscular characteristics of bulls. 34 young bulls (18 Salers and 16 Limousins) were divided into two groups with equal breed representation and equal mean growth rates, to 10 months of age. One group was housed in tying-type housing (short stalls 1.8m(2) per animal) and the other in loose housing (6.5m(2) per animal). Samples of semitendinosus (ST) and longissimus thoracis (LT) muscle were taken at slaughter at 16 months. The lactate dehydrogenase (LDH) and isocitrate dehydrogenase (ICDH) activities were measured. The proportion of isoforms LDH-M and LDH-H were determined for each muscle. Total collagen content and solubility were measured for ST alone. Fibres were classified by ATPase myofibrillar and succinate dehydrogenase activities into SO (slow oxidative), FOG (fast oxidative glycolytic) or FG (fast glycolytic), and by immunohistochemistry by reaction with monoclonal antibodies specific to slow and fast myosin heavy chain reactions into I, IIC, IIA, IIAB and IIB fibres. Compared with animals in tying-type housing, animals in loose housing presented the following: fewer carcass adipose deposits (p<0.01); for ST muscle, more collagen (p<0.01) and a reduced glycolytic metabolism, as indicated by lower LDH activity (p<0.10) and a lower proportion of FG fibres (p<0.10). In both ST and LT muscles, loose housing resulted in an increased percentage of IIC fibres (p<0.05) but did not alter the proportions of fast fibres. Modifications in ST alone were increased percentage of IIA fibres (p<0.10) and IIAB fibres (p<0.01) and a lower percentage of IIB fibres (p<0.01). Thus, for a given rate of growth, the type of housing (loose or tying-type) influenced contractile characteristics, especially in muscles involved in movement. PMID- 22061349 TI - Effect of genetic origin, diet and weaning weight on carcass composition, muscle physicochemical and histochemical traits in the rabbit. AB - Fifty rabbits originating from the crossing of one dam strain with three sire strains, Hy+, INRA 9077 and INRA 3889, were studied. The adult body weights of the sire strains were 5.1, 4.1 and 3.1kg, respectively. After weaning, the Hy+ and the INRA 9077 rabbits were fed either an H (11.99MJ DEkgDM(-1)) or L diet (9.67MJ DEkg DM(-1)). The INRA 3889 rabbits were fed only the H diet. In each of these five blocks, two weaning weights were studied and the rabbits were slaughtered when the average body weight of each block reached 2.5kg. Slaughter yield, carcass fatness and hindleg meat to bone ratio were determined. Muscular tissue was described using (1) physicochemical criteria (ultimate pH, L(*)a(*)b(*) colour) of the biceps femoris (BFE), tensor fasciae latae (TFL) and semimembranosus accessorius (SMA) muscles and (2) histochemical characteristics of the longissimus lumborum muscle (LL) through computerised image analysis (fibre type composition, cross-sectional area). At slaughter, the rabbits of INRA 3889 sire origin, which had the highest degree of maturity (72%), gave the best slaughter yield (p<0.01), the heaviest reference carcass weight (p<0.01), and highest LL proportion (p<0.01), hindleg meat to bone ratio (p<0.05) and fatness (p<0.01); their LL muscle showed the lowest percentage of betaR fibres, while the cross-sectional area of their muscular fibres was the highest (p<0.05). When all sire * diet combinations were put together, the heavier the weaning weight, the lower the daily gain (p<0.01) and the lightness (L*) of thigh muscles (p<0.05). The lower the DE content of the diet, the lower the growth rate, the slaughter yield, the reference carcass weight (p<0.01) and the cross-sectional area of all types of muscle fibres of the rabbits of both Hy+ and INRA 9077 sire origin. PMID- 22061350 TI - Inhibition of Lipid Oxidation in Chicken by Carnosine and Dietary alpha Tocopherol Supplementation and its Determination by Derivative Spectrophotometry. AB - The antioxidant activity of carnosine in chicken meat, and its relationship to dietary alpha-tocopherol supplementation, was examined. Broiler chickens were fed diets containing 30 (basal) or 200 (supplemental) mg alpha-tocopherol acetate kg( 1) feed for 6 weeks. Raw and cooked thigh meat patties containing carnosine (0 1.5%) were prepared. Lipid oxidation, during refrigerated storage under fluorescent light, was assessed by monitoring malonaldehyde formation, using the TBA assay and single wavelength (conventional) or first derivative spectrophotometry. In raw patties, added carnosine improved oxidative stability for up to 10 days of refrigerated storage. In cooked patties, the 1.5% carnosine level provided the best antioxidant protection during 7 days of storage. Carnosine (1.5%) was at least as effective as supplemental alpha-tocopherol in improving the oxidative stability of raw and cooked patties. The presence of both antioxidants had an additive effect on oxidative stability. Overall, the use of derivative spectrophotometry improved the specificity of the TBA assay for monitoring MDA formation in refrigerated meats. PMID- 22061351 TI - Porcine bone marrow: extraction procedure and characterization by bone type. AB - Data on porcine and bovine bone marrow composition indicate high calcium content, which may be erroneously elevated owing to the marrow recovery process. A method of bone marrow recovery was developed that involved passing marrow extracted from bone through a filter-press mechanism to remove very fine bone particles and dust, allowing a more accurate analysis of marrow. Calcium values were reduced approximately 90% and ash values reduced more than 50% compared to other reported data. The new recovery method did not require sawing away the hard bone and it removed particulate that may have interfered with analyses. Bone marrow was characterized by bone type. Rib bone marrow had higher protein, iron, non-heme iron and total pigment than scapula, aitch/hip bone or vertebrae marrow. Fat ranged from 17.81 to 26.76% and calcium ranged from 27.25 to 44.33mg 100g(-1) among bone types. The pH of bone marrow ranged from 7.14 to 7.53. Bone marrow appears to contribute to some of the properties of meat obtained from advanced meat recovery systems. PMID- 22061352 TI - Sodium Lactate/Sodium Tripolyphosphate Combination Effects on Aerobic Plate Counts, pH and Color of Fresh Pork Longissimus Muscle. AB - The objective of this study was to evaluate the effects of sodium lactate/sodium tripolyphosphate pump combinations on the characteristics of pork loins. The product was manufactured to simulate fresh pumped pork loins currently available in the retail market. Paired fresh pork loins (longissimus muscle), pumped to contain 0, 1 or 2% sodium lactate (SL) and/or 0, 0.2 or 0.4% sodium tripolyphosphate (STP) were vacuum packaged and stored at 4 degrees C for 28 days. In pork containing 0.4% STP, samples with 1 or 2% SL had lower pH values than those with 0% SL. Pork containing 1 or 2% SL generally had lower aerobic plate counts than those with 0% SL. Pork with 0.4% STP was darker (lower L* value) and redder (higher a* value) than that with 0 or 0.2% STP. When aerobic plate counts and color characteristics are used as the criteria, the optimum SL/STP combination for solutions used to pump fresh pork loins that are vacuum packaged and held under refrigeration was 1% SL with 0.2% STP. PMID- 22061353 TI - The influence of final conditions on meat colour in light lamb carcasses. AB - Tristimulus values (X, Y, Z) and CIELAB colourimetric coordinates have been measured in m. Longissimus dorsi and m. Triceps braquialis caput longum muscles in 86 light carcasses of lambs from different origins. By applying to these data different mathematical methods (ANOVA, Discriminant Analysis, Principal Components Analysis and Cluster Analysis) we have obtained a good classification of these animals in groups, which has been established according to the different final conditions (feeding or storage). In this way, the percentage of animals accurately classified into their group is 94.2%. Worse results were obtained (84.9%) if the animals were grouped taking their breed or/and origin as a reference. PMID- 22061354 TI - Comparative study of low-field NMR relaxation measurements and two traditional methods in the determination of water holding capacity of pork. AB - The correlation between transverse relaxation, T(2,) and water holding capacity (WHC) determined either by Honikels bag method (Honikel, 1998) or centrifugation has been investigated in meat samples from m. longissimus dorsi (LD) 24 h post mortem from 74 pigs. Bi-exponential analysis of the transverse relaxation, T(2), showed highly significant correlations between both the two NMR time constants (T(21),T(22)) and water holding capacity determined by both Honikels bag method (r(T(21))=-0.72 and r(T(22))=0.77) and centrifugation (r(T(21))-0.50 and r(T(22))=0.75). This shows that transverse relaxation measurement is an efficient method for determination of water holding capacity in pork. Significant correlations were also found between T(21) and T(22) measured 24 h post mortem and pH measured at various time post mortem. This indicates that transverse relaxation, T(2), reflects pH-induced structural changes occurring in muscles post mortem. PMID- 22061355 TI - Characterization of different strains of broiler chicken by carcass measurements, chemical and physical parameters and NIRS on breast muscle. AB - The aims of the work were: to investigate the effect of chicken strain on chemical composition and colour parameters of fresh breast muscle; to evaluate the results obtained using different illuminants (A, C and F); to verify the possibility of predicting some meat features by near infrared reflectance spectroscopy (NIRS) of freeze-dried breast muscle. The trial was carried out on 39 chicken broilers from three strains, differing in body size, slaughtered at 30 days of age. Fresh breast samples were different only in ash content (P<0.01). Illuminant effect was highly significant for all colour variables, depending on the major wavelength characteristics of each illuminant. Significant differences among strains were detected in redness values. The NIRS technique was very accurate to predict fat content of muscle (R(2)c=0.98, SEC=0.20). These findings may have practical importance to improve instrumental procedures for on-line evaluation of poultry meat quality. PMID- 22061356 TI - Evaluation of electrical stunning methods using alternative frequencies in commercial rabbits. AB - The stages of recovery and spontaneous physical activity were evaluated using five methods of electrical stunning with variable voltage and frequency in an experiment with commercial rabbits (n=50). The recovery stages, evaluated by video recording, were: the tonic phase; the clonic phase; the corneal reflex; the resumption to rhythmic breathing, the response to painful stimuli and the hindleg posture. In a second rabbit sample (n=96) the muscular pH of the m. biceps femori and the pH of the m. longissimus dorsi were recorded. The levels of stunning were acceptable in all rabbits, with small variations among methods, especially with respect to the last stage of recovery. The period of insensibility before the appearance of the rhythmic breathing was an average of 30.14 +/- 0.5 s long. There was no significant effect on meat pH at 24 h. PMID- 22061357 TI - Electrical stimulation - when more is less. AB - This study was conducted to determine whether electrical stimulation per se can be omitted when other electrical inputs to beef carcasses (stunning and immobilisation) are used. In addition, we investigated which sample preparation method at 1 day post mortem (p.m.), cooked fresh, frozen, or after thawing, had the best predictive value for shear force after ageing of the muscle. Beef carcasses were electrically immobilized (75 V, 15 Hz) before and during exsanguination for 20 or 80 s and meat quality characteristics of the longissimus were determined at 1 and 7 days post mortem. Muscles from carcasses receiving the higher electrical input were similar in tenderness at 1 day p.m., but tougher at 7 days p.m. This result could be explained by the effect of muscle shortening and post mortem proteolysis on tenderness. These results indicate that even low electrical input during immobilization can adequately stimulate carcasses and avoid cold shortening. Freezing samples resulted in a considerable improvement in tenderness and cooking samples from the frozen state had the highest predictive value for tenderness after ageing. In a second experiment it was determined that freezing and thawing did not result in appreciable differences in cooking loss or proteolysis. The tenderising effect of freezing may be explained by tissue damage due to ice formation. PMID- 22061358 TI - Diverse lamb genotypes. 3. Eating quality and the relationship between its objective measurement and sensory assessment. AB - The effect of genotype on eating quality was evaluated on m. Longissimus thoracis et lumborum (LTL) muscle of 60 lambs. The lambs were sired by a selection of Texel (T), Poll Dorset (PD), Border Leicester (BL) and Merino (M) rams, crossed with Border Leicester x Merino (BLM) and Merino (M) ewes giving six genotypes (TxBLM, PDxBLM, TxM, PDxM, BLxM and MxM). The relationships between sensory panel assessment of eating quality attributes and pH, cooking loss and shear force were also investigated. No significant differences were observed between genotypes for panel assessment of tenderness, juiciness, aroma liking, aroma strength, flavour liking, overall acceptability and rating. MxM lambs had a significantly (P<0.05) higher flavour strength than BLxM lambs. pH was a poor indicator of any eating quality attributes, except aroma strength (r=0.3, P<0.05). Warner Bratzler shear force value (WB) and tenderness showed a significant (P<0.001) negative correlation (-0.7). Tenderness, flavour and juiciness were the most important sensory attributes, explaining 86.5% of the total variation in overall acceptability. PMID- 22061359 TI - Quantitative competitive (QC) PCR for quantification of porcine DNA. AB - Many meat products nowadays may contain several species in different proportions. To protect consumers from fraud and misdeclarations, not only a qualitative but also a quantitative monitoring of ingredients of complex food products is necessary. DNA based techniques like the polymerase chain reaction (PCR) are widely used for identification of species but no answer to the proportional amount of a certain species could be given using current techniques. In this study we report the development and evaluation of a quantitative competitive polymerase chain reaction (QC-PCR) for detection and quantification of porcine DNA using a new porcine specific PCR system based on the growth hormone gene of sus scrofa. A DNA competitor differing by 30 bp in length from the porcine target sequence was constructed and used for PCR together with the target DNA. Specificity of the new primers was evaluated with DNA from cattle, sheep, chicken and turkey. The competitor concentration was adjusted to porcine DNA contents of 2 or 20% by coamplification of mixtures containing porcine and corresponding amounts of bovine DNA in defined ratios. PMID- 22061360 TI - Measuring pork color: effects of bloom time, muscle, pH and relationship to instrumental parameters. AB - To evaluate factors affecting pork color, the gluteus medius (GM), longissimus lumborumetthoracis (LT), semimembranosus (SM), biceps femoris (BF), and triceps brachii (TRI) muscles from pork carcasses of varying ultimate pHs were allowed to bloom for 30 min. L*, a*, and b* values, hue angle, chroma and visual color were determined. Color was evaluated using HunterLab (illuminants A, C, D(65) and F) and Minolta (illuminants C and D(65)) Spectrocolorimeters. LT had the highest L* value (51.31; TR=39.93) and hue angle (59.36; TR=46.94), and the lowest a* (7.52; TR=12.88) value. L* value was unaffected by bloom time; hue angle stabilized after 5 min, a* and b* values after 10 min and chroma after 20 min. Using the Minolta/illuminant D65, visual color best correlated with b* and L* values (r= 0.94 and -0.89) of LT. Using the Hunter/illuminant C, visual color correlated with L* value of LT, GM, BF and SM (r >-0.90 for each). Overall, the instrumental measure that best related to visual color was L* value. PMID- 22061361 TI - Assessment of the antioxidant potential of natural food and plant extracts in fresh and previously frozen pork patties. AB - Antioxidant activities of aloe vera, fenugreek, ginseng, mustard, rosemary, sage, soya protein, tea catechins and whey protein concentrate (35% protein) were evaluated in pork patties prepared from both fresh and previously frozen (-20 degrees C) pork. Chemical analysis showed test ingredients to be more effective in reducing lipid oxidation in patties made from previously frozen pork. Tea catechins, rosemary and sage were identified as being the most effective antioxidants with potency decreasing in the following order: tea catechins>rosemary>sage. Optimum addition rates of these ingredients suggested levels of 0.25, 0.10, 0.05% for tea catechins, rosemary and sage, respectively. Soya protein (0.10%) increased meat redness in fresh pork patties producing significantly (P<0.05) higher Hunter 'a' values over the controls on days 0, 3 and 6. However, fenugreek (0.01%) was more effective in increasing Hunter 'a' values in patties manufactured from previously frozen pork. No significant (P>0.05) differences in Hunter 'L' and 'b' values were found between test and control samples on storage. The pH values of tea catechins, sage and soya protein fluctuated over time. Fresh pork patties with mustard and ginseng caused an initial decrease followed by a subsequent increase in pH values. Fenugreek caused an initial increase in pH values followed by a decrease from day 3 onwards. PMID- 22061362 TI - Estimation of the carcass composition of yearling bulls of "Asturiana de los Valles" breed from the dissection of a rib joint. AB - To evaluate different methods of estimating bovine carcass composition, seventy yearling bulls of the "Asturiana de los Valles" beef breed were slaughtered and their carcass composition estimated by a commercial dissection of the right half carcass and by tissular dissection of the 6th and 10th rib of the left half carcass. Correlation and regression analyses were used to identify the most accurate predictors of carcass composition. In simple regression, the percentage of lean in the 10th rib was the most accurate predictor (r=0.88; P<0.001) of the lean proportion in the carcass and the percentage of fat in the 6th rib was the best predictor (r=0.90; P<0.001) of the carcass fat content. The correlation coefficients for estimating the bone percentage in the carcass from the bone proportion in the ribs (6th and 10th) were low (r=0.63 and 0.51 respectively), although significant (P<0.001) and the coefficient improved when the proportion of lean in the ribs was used as predictor (r=0.78 and 0.70 for the 6th and the 10th rib respectively). In multiple regression, the addition of more regressors of the rib composition and carcass traits, such as carcass hot weight, the carcass fatness score and the weight of the kidney knob and channel fat, led to an improvement (P<0.05) in accuracy for some predictions. The results in general show that the accuracy of the predictions for the carcass composition obtained from dissection of both the 6th and 10th ribs was similar, although the dissection of the 10th rib tended to overestimate the proportion of fat in the carcass. Therefore, considering the carcass quartering method for the extraction of the ribs, it is proposed that dissection of the 6th rib is more appropriate than dissection of the 10th rib so as not to reduce the carcass value and obtain a good estimate of the carcass composition. PMID- 22061363 TI - Instrumental colour classification of veal carcasses. AB - Three experiments, involving over 56 000 veal carcasses, were carried out to develop a method for instrumental colour classification of veal carcasses at 45 min post mortem with the Minolta CR300. The method should produce results similar to those of the 10-point colour-system, which is currently in use in The Netherlands. In the first experiment, the colour of veal carcasses was visually assessed by three observers and instrumentally measured with two Minolta CR300 devices. The average of the results of the three observers and the two Minolta devices were used for discriminant analysis to analyse yield classification rules, which allowed to assignment of the carcasses to classes of the 10-point colour-system. Identical classifications for Minolta and observer were obtained for 63.2% of the carcasses. In the second and third experiment, the classification rules with the Minolta CR300 were used to predict the colour class. For the new samples, identical classification results were obtained for 50 55% of the carcasses. In 41-44% of the carcasses the classification results differed by less than one class. The results show that the Minolta CR300 is under practical conditions able to predict the 10-point colour classes and can be used for on-line colour classification in a slaughterhouse. PMID- 22061364 TI - Cholesterol oxidation in frozen dark chicken meat: influence of dietary fat source, and alpha-tocopherol and ascorbic acid supplementation. AB - A factorial design assessed the effect of dietary fat source (beef tallow, fresh and oxidized sunflower oils, and linseed oil), and alpha-tocopheryl acetate (alpha-TA) and ascorbic acid (AA) supplementation (225 and 110 mg/kg feed, respectively) on the cholesterol oxidation product (COP) content and 2 thiobarbituric acid (TBA) values in raw and cooked dark chicken meat vacuum packaged and stored at -20 degrees C for 7 months. COP determination showed good linearity, recovery and precision. Dietary alpha-TA was highly effective in protecting raw or cooked meat from cholesterol and fatty acid oxidation, regardless of its degree of unsaturation. In contrast, AA supplementation was ineffective and even promoted oxidation in raw meat from broilers fed unsaturated fat diets that had not been supplemented with alpha-TA. Oxidation values (raw or cooked meat) from alpha-TA or alpha-TA+AA supplemented diets were not statistically different (P>0.05). TBA and COP values were significantly correlated in raw samples (r=0.6466, P=0.0001). PMID- 22061365 TI - Effect of connective tissue on the shape of reflectance spectra obtained with a fibre-optic fat-depth probe in beef. AB - A fat-depth probe was fitted with optical fibres to combine depth detection with spectrophotometry and fluorometry. Measurements were made through forelimb flexor, triceps brachii and longissimus thoracis muscles on 22 beef carcasses in a meat cooler. All strong fluorescence peaks had matching strong reflectance peaks (presumably connective tissue), but some strong reflectance peaks did not have equivalent fluorescence peaks (presumably adipose tissue). When the probe stopped at full depth and a complete reflectance spectrum was obtained, no effect from adipose tissue at the optical window of the probe was detected, whereas connective tissue increased reflectance across the visible spectrum (P < 0.005). The strongest effect was at 600 nm. Thus, spuriously high reflectance readings obtained with a fibre-optic meat probe are more likely to originate from connective tissue than from intramuscular adipose tissue. PMID- 22061366 TI - Changes in biogenic amine and polyamine contents in slightly fermented sausages manufactured with and without sugar. AB - The effect of sugar omission on biogenic amine contents of slightly fermented sausages during ripening and storage was evaluated. Two batches of spontaneously fermented sausages were produced with and without sugars in two different trials at pilot-plant scale. Ripened sausages were stored at 4 and 19 degrees C for a further 20 days. Tyramine and cadaverine were the main amines formed during ripening, their contents being significantly higher in batches without sugar. High counts of LAB and Enterobacteriaceae could be associated with the production of tyramine and cadaverine, respectively. The occurrence of putrescine depended on the trial and batch. Sausages without sugar contained more putrescine than those with sugar in trial 1, but this was not repeated in trial 2, in which a high production of agmatine occurred. Tryptamine and phenylethylamine were only detected in the later stages of ripening, their contents also being higher in sausages without sugar. Biogenic amine contents generally rose during storage at 19 degrees C, the increase being especially important for cadaverine and tyramine in sausages without sugar. Levels of spermidine and spermine remained constant during ripening and decreased slightly during storage. Sugar omission is not recommended because it might increase biogenic amine accumulation during the manufacture and storage of slightly fermented sausages. PMID- 22061368 TI - Effect of feeding system on the growth and carcass characteristics of Iberian pigs, and the use of ultrasound to estimate yields of joints. AB - Forty three-castrated male Iberian pigs of the Torbiscal line with an average initial weight of 102.27kg were used. A group of 22 pigs was fed according to the traditional way in free-range conditions with acorn and grass from November to January. Another group of 21 animals was fed 3.72kg/day of a conventional feed that contained 12.53MJME/kg, 16.21% crude protein, 4.94% fat and 6.64% of crude fiber, during the same period. Measurements of backfat thickness and Longissimus dorsi muscle area at the last rib were taken by means of a real-time ultrasound device (Kretz Technick Inc., 600 V-V2.32, Sonovet, Austria) in all pigs before slaughter. After slaughter, carcass, ham and foreleg weights and backfat and muscle area measurement from the last rib chop were recorded. The average daily gain, carcass yield, fat thickness, loin area, ham weight and proportion of hams were significantly higher (P<0.05) in the pigs fed in confinement than in those fed extensively (653.36g, 77.97%, 56.46mm, 3031mm(2), 22.26kg and 14.32% vs 501.48g, 76.94%, 51.74mm, 2673mm(2), 21.52kg and 13.79%, respectively). This paper shows the prediction equations for hams, forelegs and total hams and forelegs weights and proportions with respect to slaughter weight and live ultrasound measurements in pigs fed either extensively or in confinement. The ultrasound measurements better predicted the carcass cuts absolute amounts (R(2)=0.591-0.875) than the carcass cuts proportions (R(2)=0.23-0.40). The use of real-time ultrasound should be used with caution to predict the absolute quantities of hams and forelegs from Iberian pigs since the ultrasound measurements are only moderately accurate. PMID- 22061369 TI - Effect of antioxidants on stabilization of meat products fortified with n-3 fatty acids. AB - The effects of an n-3 oil emulsion, with and without added antioxidants, on lipid oxidation in n-3 polyunsaturated fatty acid (PUFA)-fortified meat products were studied. An emulsion of n-3 PUFAs was prepared (25% algal oil, 2.5% whey protein isolates, 10mM sodium citrate, 0.2% potassium sorbate, 500ppm of 70% mixed tocopherols, 100MUM EDTA, pH 3, pasteurized at 75 degrees C for 30min) and incorporated into fresh ground turkey, and fresh pork sausage (20% fat) to achieve a concentration of 500mg n-3 PUFA/110g meat. An antioxidant combination containing rosemary (0.2% w/w; radical quencher), citrate (0.5% w/w; sequestrant) and erythorbate (1g/kg product; reductant) was prepared and incorporated into ground turkey patties (5cm dia, 1.5cm thick) or fresh pork sausages (5cm dia, 1.5cm thick). Meat products were stored at 4 degrees C or -18 degrees C and analyzed for color (L*, a*, b* values), lipid oxidation (TBARS and lipid hydroperoxides) and n-3 PUFA profile. a* Values of refrigerated ground turkey patties decreased with storage, and an antioxidant combination effect was observed after 4 days (P<0.05). For fresh pork sausages at 4 degrees C, control+antioxidant (CON+ANTI), and n-3+antioxidant (n-3+ANTI) groups showed greater a* values than controls (CON) indicating that the antioxidant combination stabilized meat color. TBARS and lipid hydroperoxides of both n-3 PUFA-enhanced meat products increased with storage (P<0.05); there were no significant changes in TBARS or lipid hydroperoxides for treatments containing the antioxidant combination (P<0.05). The actual level of n-3 PUFA incorporation in both meat products was greater than 87%; n-3 PUFA concentrations did not change within any treatment during storage (P>0.05). These results provide support for including antioxidant protection in n-3 PUFA fortified meat products. PMID- 22061370 TI - Functionality of cow beef in coarse and fine ground model systems. AB - Patties and sausage batters were made from trimmed brisket, chuck, striploin, hindshank, silverside, thick flank and rib trim from grass-fed Friesian cows. Functionality of each meat cut was determined from cook yield and true stress and strain of cooked sausage batters and cook yield, dimensional changes and peak force of cooked patties. Colour of raw and cooked slices from the meat cuts and cooked batters was evaluated using a colorimeter and a consumer panel. Composition of raw meat from all cuts was similar; chuck and rib trim had higher pH values and were more red than meat from other cuts. Cooked batters from striploin, chuck and hindshank had higher stress and strain values than gels from other cuts. Patties made from thick flank and striploin were the softest and had the highest cook yield. Batters and patties made from meat with higher salt soluble protein content retained more water and fat on cooking, were more cohesive and had higher bind strengths. Manufacturers can use functionality characteristics to select meat for specific products. PMID- 22061371 TI - Effect of freezing temperature, thawing and cooking rate on water distribution in two pork qualities. AB - The effects of freezing temperature (-20 versus -80 degrees C) in combination with long-term freezer storage (-20 degrees C) on water mobility and distribution in pork of two qualities (normal and high ultimate pH) were explored using low field NMR T(2) relaxometry. A marked effect of freezing temperature on the characteristics of intra- and extramyofibrillar water (T(2) relaxation times) in the thawed pork was demonstrated, implying that the freezing temperature in combination with prolonged freezer storage affects the distribution and chemical physical state of water in the thawed meat. Determination of technological properties (thawing and cooking loss) revealed that the observed T(2) variations related to water distribution and water properties, which were found to be consistent with the degree of structural damage assessed by light microscopy, also were reflected in the technological quality of the meat. Low freezing temperature in combination with prolonged freezer storage was associated with increased thawing and cooking loss. In addition, pH in the fresh meat had a pronounced effect on the distribution of myofibrillar water, as a more homogenous pore size distribution was evident in meat with high pH compared with normal pH. A clear effect of cooking rate on the T(2) relaxation characteristics in the cooked pork was also demonstrated, probably reflecting a cooking rate-induced effect on the myofibrillar structures. The effect of cooking rate on water distribution resulted in a significantly lower cooking loss upon a slow cooking rate (0.5 degrees C/min from 25 to 65 degrees C and 0.3 degrees C/min from 65 to 80 degrees C) compared with a fast cooking rate (1 degrees C/min). PMID- 22061372 TI - Prediction of body composition of Iberian pigs by means bioelectrical impedance. AB - Twelve barrow Iberian pigs with an average weight at slaughter of 109.2kg were used to evaluate bioelectrical impedance procedures to predict the body composition of live pigs. Twelve hours before slaughter pigs were weighed, and a four-terminal body composition analyser (Model BIA-101, RJL Systems, Detroit, MI) was utilized to determine resistance (R(s) in Omega) and reactance (X(c) in Omega). The length values (L in cm) were measured between detector electrodes with a flexible steel tape. Twenty four hours after slaughter the left side of each carcass was separated using a scalpel into fat, lean, bone and skin. Multiple regression equations for estimating lean, fat, bone and skin amounts and lean, fat, bone and skin proportions with respect to slaughter weight were calculated. The live weight (LW) and L independent variables predicted 85.3% and 64.3% of the variability of the lean amount and lean proportion, respectively. The LW, X(c) and L variables accounted for 96% and 91.6% of the variation in fat quantity and fat proportion, respectively. The LW and R(s) accounted for 58.9% of the variation in bone amount, and the same variables predict 79.1% of the variability of bone percentage. The R(s) and L variables explained 68% of the variability of skin quantity and LW, R(s) and X(c) predicted 83.1% of the variation of skin proportion. Results from this experiment indicate that bioelectrical impedance may be of interest for body composition prediction of live Iberian pigs. PMID- 22061373 TI - Effects of ascorbic acid, rosemary, and OriganoxTM in preventing bone marrow discoloration in beef lumbar vertebrae in aerobic and anaerobic packaging systems. AB - Treatments of 1.25% or 2.5% ascorbic acid (AA); 0.1% or 0.2% rosemary; or a combination of 0.15% OriganoxTM+0.3% AA on beef lumbar vertebrae (n=72) were evaluated for their effectiveness in preventing bone discoloration in retail packages. Vertebrae were held either 6 or 14d postmortem; cut into 2.54-cm sections; and packaged into either polyvinyl chloride film overwrap (PVC), high oxygen (80% O(2)/20% CO(2)) modified-atmosphere packages (MAP), or ultra-low oxygen (70% N(2)/30% CO(2)) MAP. Controls and vertebrae treated with 0.1% or 0.2% rosemary discolored significantly, whereas 0.15% OriganoxTM+0.3% AA was effective through d 2 of display in PVC and high-oxygen MAP. In both high- and ultra-low oxygen MAP, 1.25% AA was as effective as 2.5% AA in preventing bone discoloration. Vertebrae treated with AA or packaged in ultra-low-oxygen MAP had the largest a* values over display time. Bone discoloration was effectively prevented with AA, especially at the 2.5% concentration. PMID- 22061374 TI - Effect of a bacteriocin produced by Pediococcus acidilactici against Listeria monocytogenes and Clostridium perfringens on Spanish raw meat. AB - The inhibitory effect of a bacteriocin, produced by Pediococcus acidilactici, against Listeria monocytogenes and Clostridium perfringens on Spanish raw meat surface, was evaluated by in situ assays. Samples were incubated with the bacteriocin and then with a culture of the pathogenic bacteria. The treatment with 500, 1000 or 5000 bacteriocin units/ml (BU/ml) reduced the counts of L. monocytogenes after storage at 15 degrees C during 72h by 1, 2 or 3 log cycles and with 1000 or 5000 BU/ml after storage at 4 degrees C during 21 days by 2.5 or 3.5 log cycles, respectively, compared to the control. With C. perfringens a bacteriostatic effect could be observed. PMID- 22061375 TI - Freezing of meat raw materials affects tyramine and diamine accumulation in spontaneously fermented sausages. AB - Biogenic amine accumulation was studied in spontaneously fermented sausages (Fuet) manufactured from unfrozen-fresh meat (U-sausages) and frozen-thawed meat (F-sausages). The aim was to investigate whether the frozen storage of raw materials affects the microbial composition and its aminogenic activity during sausage fermentation. Tyramine was the major amine in all sausages. Although the final levels were similar, tyramine accumulated more rapidly in F-sausages, which contained putrescine as the second amine. By contrast, U-sausages accumulated much more cadaverine than putrescine. F-sausages showed a slightly lower pH and free amino acid content as well as higher counts of technological flora (lactic acid and gram positive catalase positive bacteria) and lower counts of enterobacteria. Therefore, to freeze the meat raw materials for few days before sausage manufacture could be a useful practice, especially for the artisan fermented sausages (without starter), because it helps to reduce enterobacteria development and cadaverine production. PMID- 22061376 TI - The efficacy of a vitamin D(3) metabolite for improving the myofibrillar tenderness of meat from Bos indicus cattle. AB - The influence of a once only administration of a metabolite of vitamin D(3) (HY.D((r))-25-hydroxy vitamin D(3)) on myofibrillar meat tenderness in Australian Brahman cattle was studied. Ninety-six Brahman steers of three phenotypes (Indo Brazil, US and US/European) and with two previous hormonal growth promotant (HGP) histories (implanted or not implanted with Compudose((r))) were fed a standard feedlot ration for 70d. Treatment groups of 24 steers were offered daily 10g/head HY.D((r)) (125mg 25-hydroxyvitamin D(3)) for 6, 4, or 2d before slaughter. One other group of 24 steers was given the basal diet without HY.D((r)). Feed lot performance, blood and muscle samples and carcass quality data were collected at slaughter. Calcium, magnesium, potassium, sodium, iron and Vitamin D(3) metabolites were measured in plasma and longissimus dorsi muscle. Warner-Bratzler (WB) shear force (peak force, initial yield) and other objective meat quality measurements were made on the longissimus dorsi muscle of each steer after ageing for 1, 7 and 14d post-mortem at 0-2 degrees C. There were no significant effects of HY.D((r)) supplements on average daily gain (ADG, 1.28-1.45kg/d) over the experimental period. HY.D((r)) supplements given 6d prior to slaughter resulted in significantly higher (P<0.05) initial yield values compared to supplements given 2d prior to slaughter. Supplementation had no significant effect on meat colour, ultimate pH, sarcomere length, cooking loss, instron compression or peak force. There was a significant treatment (HY.D((r))) by phenotype/HGP interaction for peak force (P=0.028), in which Indo-Brazil steers without previous HGP treatment responded positively (increased tenderness) to HY.D((r)) supplements at 2d when compared with Indo-Brazil steers previously given HGP. There were no significant effects of treatment on other phenotypes. HY.D((r)) supplements did not affect muscle or plasma concentrations of calcium, potassium or sodium, but did significantly decrease plasma magnesium and iron concentrations when given 2d before slaughter. There were no detectable amounts of 25-hydroxyvitamin D(3) in the blood or muscle of any cattle at slaughter. PMID- 22061377 TI - A mapping method for the description of Warner-Bratzler shear force gradients in beef Longissimus thoracis et lumborum and Semitendinosus. AB - A novel approach to mapping Warner-Bratzler shear of whole muscles was explored. The procedure was used on the Longissimus thoracis et lumborum (LTL) and Semitendinosus (ST) from six beef cattle by first marking skeletally defined anatomical landmarks on the muscle in situ. After removal from the carcass, further divisions were made while preserving sample orientation during cooking and preparation for shearing. Shear gradients were observed in all planes of the LTL, particularly the medial-lateral. The mid-section of the ST had the lowest shears while superficial locations of the cross-section had greater values. Muscle comparison indicated the ST was more uniform than the LTL. The mapping technique was subsequently used to identify localized effects of altered carcass suspension on shear values and sarcomere length in the lumbar Longissimus from four beef cattle. This mapping method will provide guidance for further intensive investigation across the carcass musculature and under varying carcass conditions. PMID- 22061378 TI - Effects of slaughter weight on carcass composition and meat quality in pigs of two different growth rates. AB - Three hundred and forty (340) Duroc*(Landrace*Yorkshire) crossbred piglets were allotted to a 2*2*3 factorial design experiment. The independent variables were the growth rate (fast: around -10 days at 100kg and slow: around +2 days at 100kg), based on two different EBV's (estimated breeding value) of the sire-line for age, the sex (barrows and gilts) and the live weight at slaughter (107, 115 and 125kg). A sub-population of 119 pigs (10 carcasses per treatment) was selected for the carcass and meat quality evaluation trials. As live weight increased there were significant increases in hot carcass weight and dressing percentage (P<0.05). Lean, fat and bone proportions were not affected by weight. Gilts had higher lean proportion (P<0.05) than barrows. Furthermore, carcasses of fast growing pigs were fatter (P<0.05) than those of slower growing ones. Loin muscle pH, drip loss and reflectance values did not vary significantly with any of the treatments. Intramuscular fat was higher in barrows (P<0.05) than in gilts and soluble collagen content decreased with increasing weight (P<0.05). Muscle protein (%) increased (P<0.05) from 107 to 115kg and gilts had a higher (P<0.05) content than castrates. No evidence was found that increasing slaughter weight detracts from carcass characteristics or meat quality. PMID- 22061379 TI - Fatty acid and sensory characteristics of beef from three biological types of cattle grazing cool-season forages supplemented with soyhulls. AB - Over two consecutive years, the effects of allocating divergent biological types of cattle (n=107) to fescue pasture without supplementation, or fescue or orchardgrass pasture with soyhull supplementation on chemical, fatty acid and sensory characteristics were investigated. Cattle from the two supplemented treatments produced beef that had increased (P<0.05) percentage lipid and decreased (P<0.05) polyunsaturated and n-3 fatty acids compared to the control. However, the n-6 to n-3 ratio was still less than four in beef from the supplemented cattle. Additionally, supplementation did not decrease (P>0.05) the CLA present in the longissimus, which can commonly occur when forage-fed cattle are supplemented concentrates. Although supplementation did not impact (P>0.05) Warner-Bratzler shear force or tenderness, supplementation of soyhulls reduced (P<0.05) the grassy flavor intensity of rib steaks when compared to the control. Biological type did not have a significant influence on most traits analyzed in this study. These results suggest that supplementation of soyhulls to cattle grazing forage can reduce grassy flavor intensity without decreasing CLA proportions, but can reduce the n-3 fatty acid proportions present in the longissimus. PMID- 22061380 TI - Characteristics of restructured beef steak with different proportions of walnut during frozen storage. AB - Physicochemical (thawing loss, cooking loss, surface shrinkage, texture, colour and lipid oxidation) and sensory properties of restructured beef steak with different levels of added walnut (0%, 10% and 20%) were determined at various times during frozen storage up to 128 days. Cooking loss (CL), Kramer shear force (KSF) and binding strength (BS) of restructured beef decreased (P<0.05) as the proportion of walnut increased. Walnut enhanced (P<0.05) lightness and yellowness and reduced (P<0.05) redness. Frozen storage did not affect (P>0.05) CL, KSF and BS of restructured beef steak. Redness decreased (P<0.05) over storage for all samples. Lipid oxidation of restructured beef steak containing walnut was not a limiting factor for frozen stability of meat products. Frozen storage had no effect (P>0.05) on the sensory quality of restructured beef steak. PMID- 22061381 TI - Activities of calpastatin, MU-calpain and m-calpain are stable during frozen storage of meat. AB - The stability of MU-calpain, m-calpain and calpastatin activity during frozen storage of pork was studied in two experiments. In experiment 1, pork longissimus muscle was stored at either -20 or -80 degrees C, and the samples were assayed at 2-3 weeks interval for calpain activity and calpastatin activity using a m calpain stock solution stored at 4 degrees C. No effects on calpain activity at either temperature were observed for up to 123 days of storage. Calpastatin activity was stable the first few weeks of storage, where after it decreased up to 143 days of storage independently of meat storage temperature. At day 143, calpastatin activity was also assayed using a newly purified stock solution of m calpain giving a calpastatin activity equal to the activity measured day 0 using the original m-calpain stock solution. The m-calpain stock solution was unstable during storage at 4 degrees C and the activity decreased in a linear manner and was highly related to the observed decrease in calpastatin activity during storage. In experiment 2, meat was stored as in experiment 1 and was assayed at 2 3week intervals for calpastatin activity using a m-calpain stock solution stored at either 4 or -80 degrees C. As in experiment 1, the measured activity of calpastatin decreased during storage using m-calpain stock solution stored at 4 degrees C and this decrease was highly correlated to the decrease in the activity of the m-calpain stock solution. The activity of the m-calpain stock solution stored at -80 degrees C was constant during storage period of 153 days and likewise was the calpastatin activity measured using this stock solution. The relation between measured calpastatin activity and storage time of m-calpain stock solution was tested by adding, to a calpastatin assay, up to 10MUL of a partly inactivated m-calpain solution. A negative relationship was observed between added inactivated m-calpain and measured calpastatin activity which suggests that the inactive m-calpain molecules mask some of the binding sites on calpastatin and thereby prevent some of the active m-calpain molecules from binding to calpastatin. This would underestimate the measured calpastatin activity. In conclusion, the calpains as well as calpastatin are stable during frozen storage of meat, and the observed decreased in calpastatin activity is due to instability of the m-calpain stock solution used in the calpastatin assay. PMID- 22061382 TI - Effect of selection for growth rate on the ageing of myofibrils, meat texture properties and the muscle proteolytic potential of m. longissimus in rabbits. AB - The effect of selection for growth rate on the degradation of the myofibrillar proteins and on meat texture properties of rabbit longissimus muscle at two ageing times (1 and 7 days) was studied as well as its effect on the proteolytic potential of the muscle. Two groups of contemporary animals (20 rabbits per group), one selected for growth rate (S) for 14 generations and the other unselected control group (C) were compared. The control group was formed from the offspring of the embryos belonging to the 7th generation and was compared with selected animals belonging to 21st generation. Myofibrillar protein degradation was studied by SDS-PAGE electrophoresis (12.5% and 4-15% polyacrylamide gels) followed by densitometric analysis of the pherograms. Texture properties were evaluated by Warner-Bratzler (WB) test and Texture profile analysis (TPA). The activities of proteolytic enzymes calpains and cathepsins and of their inhibitors were determined in the muscle at 24h. Densitometric analysis of the pherograms of samples aged 7 days showed an extra 30kDa band and the disappearance of a band with higher molecular weight than the myosin heavy chain with respect to samples aged 24h in both groups of rabbits. TPA results showed that cohesiveness was significantly lower in meat at 7 days than at 24h (P<0.0001), whereas springiness and chewiness presented a clear tendency to be lower at 7 days than at 24h (P=0.0646 and P=0.0764, respectively). Regarding the genetic type, S animals presented higher hardness and chewiness than C rabbits. Shear firmness (WB test) was significantly (P<0.0001) higher for S group, whereas no significant differences in shear force and area were found. No significant effect (P>0.05) of ageing time was detected using WB test. Selection for growth rate did not affect the activities of proteolytic enzymes or their inhibitors. PMID- 22061383 TI - Influence of slaughter season and sex on fatty acid composition, cholesterol and alpha-tocopherol contents on different muscles of Barrosa-PDO veal. AB - The influence of slaughter season and sex on intramuscular total lipids (ITL) neutral lipid (NL) and phospholipid (PL) compositions, cholesterol and alpha tocopherol contents were evaluated in Biceps femoris (Bf), Longissimus dorsi (Ld) and Supraspinatus (Ss) muscles from 92 Barrosa-PDO (Protected Denomination of Origin) calves. ITL content in Bf muscle was affected by slaughter season and sex whereas NL content was only affected by slaughter season. Neither sex nor slaughter season influenced cholesterol and alpha-tocopherol contents in the muscles under study. Concerning NL composition, sex was an important source of variation on the proportions of total SFA and MUFA in all muscles. Irrespective of the considered muscle, males had higher total SFA but lower total MUFA and MUFA/SFA contents than females. Slaughter season influenced C18:2 cis-9 trans-11 (CLA) content in Bf (P<0.01) and in Ss muscles (P<0.05) with calves slaughtered in autumn showing higher values than their counterparts. Total MUFA, n-3 PUFA and n-6/n-3 ratio contents in Ld muscle were also affected by slaughter season. Regarding PL composition, slaughter season*sex interaction affected total SFA, PUFA/SFA and n-6 PUFA contents in Bf and Ss muscles. In addition, this interaction influenced total MUFA (P<0.05) in Bf muscle and total PUFA (P<0.01) in Ss muscle. CLA content in PL from Ld was influenced by sex (P<0.05) and by slaughter season (P<0.01), with females slaughtered in autumn presenting the highest content. These results clearly indicate that sex and slaughter season are important factors that influence the fatty acid composition of Barrosa-PDO veal. PMID- 22061384 TI - Head current during and blood splashes after electrical stunning in relation to characteristics of the pig's body. AB - In order to evaluate electrical stunning in relation to the incidence of blood splashes, meat quality and carcass quality parameters, 2035 pigs, heterozygous for the halothane gene, were observed during slaughter at a commercial slaughterhouse. The head current during electrical stunning is significantly higher (P<0.01) in gilts with a lower live weight (P<0.0001) or cold carcass weight (P<0.0001) and a higher lean meat percentage (P<0.0001). Also the incidence of blood splashes in the ham is significantly higher in gilts (P<0.0001) with a higher lean meat percentage (P=0.0028; odds ratio=1.11), a lower live weight (P=0.003; odds ratio=0.98) and a lower type number (P=0.0074; odds ratio=0.64). For barrows, no significant parameters were revealed. These results suggest that the variability in incidence of blood splashes can be explained by the variability of current density depending both on sex and body characteristics. Thus, electrical stunning can be improved by providing an energy level, based on the body characteristics of the pig. PMID- 22061385 TI - Quantification of muscle, subcutaneous fat and intermuscular fat in pig carcasses and cuts by magnetic resonance imaging. AB - The aim of this study was to determine the suitability of magnetic resonance imaging (MRI) to predict tissue composition of pig carcasses and cuts. Twenty four pig carcasses were cut into the four primary cuts that were analyzed with a low field MRI imager before a total dissection. Images were then processed to identify and quantify pixels representing muscle, subcutaneous fat and intermuscular fat fractions. MRI provided a good prediction of muscle content in cuts and carcasses, with R(2) ranging from 0.970 to 0.997. The prediction was slightly less accurate for total fat (0.951?R(2)?0.986) or subcutaneous fat (0.918?R(2)?0.994). Finally, the prediction of intermuscular fat content in considering intermuscular fat classified pixels was acceptable only for the belly (R(2)=0.837). PMID- 22061386 TI - Improving low fat meatball characteristics by adding whey powder. AB - In this study whey powder (WP) at levels of 0%, 2% and 4% was added to beef meatballs formulated with 5%, 10% and 20% fat levels. Raw and cooked meatballs were analyzed for protein, fat, moisture, ash and pH. Meatballs were evaluated for cooking characteristics, juiciness, colour parameters (L*,a*,b*) and sensory properties. Addition of WP did not affect fat and protein contents of meatballs. Addition of 2% or 4% WP significantly increased cooking yield regardless of the fat level. Both fat level and WP level significantly affected fat retention values of meatballs. Incorporating WP had no effect on meatball juiciness. Addition of WP increased fat and moisture retention of meatballs. Twenty percent fat resulted in higher L* and lower a* values. Adding WP resulted in higher L* values but WP had no effect on a* and b* values. WP had no detrimental effect on sensory properties. PMID- 22061387 TI - Investigating the concept of meat quality from the consumers' perspective: The case of Greece. AB - Recent unfortunate food incidents increased consumers' concern about food and especially meat quality. The perception that meat is a hazardous commodity to consume resulted in a stabilization of the, so far increasing, meat consumption in Greece, as well as in the EU. The present survey aims to identify the general trends of meat consumption in Greece, define through factor analysis the way consumers perceive the concept of meat quality and explore by means of cluster analysis the existence of specific consumer types in relation to meat quality perceptions, with clear-cut and statistically solid socio-demographic and behavioural profile .The frequency of meat purchasing and consumption is particularly high, while meat is present in the everyday plate of Greeks in almost any expression of their family and social life. Meat preference is mainly evaluated on the basis of pleasure derived from taste, which has to be evaluated according to visual quality cues (e.g., colour, leanness, etc.). Different consumer types with clear-cut profile are found to evaluate meat quality differently, based on different quality dimensions, such as visual quality, labels and brand name, nutritional value and microbial or chemical safety. PMID- 22061388 TI - A note on the incidences of Salmonella spp., Listeria spp. and Escherichia coli O157:H7 serotypes in Turkish sausage (Soudjouck). AB - The incidence of Salmonella spp., Listeria monocytogenes and Escherichia coli O157:H7 was determined in 100 Turkish sausage (soudjouck) samples collected from shops and markets in the Afyon province, Turkey. Salmonella spp. were detected in 7% of the samples. All of the isolates were S. enterica Paratyphi B. In addition, Listeria spp. were detected in 9% of the samples. Its distribution was 7% L. monocytogenes and 1% each of L. ivanovii and L. innocua. Serological study of the seven L. monocytogenes isolates showed that three of these were 1/2 ab, three were 5/6 ab and one was 1 ab. E. coli O157:H7 was not detected in any of the samples. The pH values of the samples ranged from 4.8 to 6.5. In conclusion, increasing number of listeriosis and salmonellosis cases in Turkey and the contamination levels found indicate that risk assessment and improved preventive measures are required for these sausages. PMID- 22061389 TI - 53rd international congress of meat science and technology, beijing, china, 5 10th august 2007. PMID- 22061390 TI - Stratification of toughness in beef roasts. AB - Most meat scientists adopt a reductionist approach to the study of meat toughness, taking a few intramuscular cores from one or more muscles to simplify the enormous complexity of toughness in all the retail cuts derived from a whole carcass. This is a valid approach to a complex problem, but we should also start to consider how consumers respond to bulk meat such as steaks and roasts. Probing whole roasts reveals a complex internal structure, detectable by both connective tissue fluorescence and resistance to penetration. The dorsal aponeurosis of the Longissimus thoracis is a major connective tissue stratum in beef rib roasts and its properties are correlated with those of adjacent intramuscular connective tissues. When the aponeurosis is cooked, its reflectance first increases with protein denaturation, then decreases with gelatinisation. Heat-induced contraction is concurrent with the increase in reflectance. Gelatinisation is reduced if the aponeurosis is mechanically restrained to resist contraction. Thus, mechanical restraint interacts with heat penetration in explaining stratification of toughness in bulk meat. PMID- 22061391 TI - Mechanisms controlling pork quality development: The biochemistry controlling postmortem energy metabolism. AB - Pale, soft and exudative (PSE) pork represents considerable economic losses for the industry due to its limited functionality and undesirable appearance. During the past several decades, exhaustive research covering various aspects of the food chain has established genotyping procedures, recommended handling practices, and quality indicators in order to reduce the incidence of inferior pork quality. Despite these efforts, there is still a relatively high occurrence of PSE pork. Development of pork quality attributes is largely governed by the rate and extent of postmortem pH decline. The combination of high temperature at low pH or abnormally low ultimate pH causes denaturation of sarcoplasmic and myofibrillar proteins, resulting in paler color and reduced water holding capacity. The pH decline is closely related to muscle energy availability and demand at or around slaughter. The postmortem degradation of glycogen through glycogenolysis and glycolysis provides ATP to help meet energy demand and decreases pH by generating lactate and H+. Therefore, the flux of metabolites through glycolysis, the involvement of energy signaling pathways that modulate glycolytic activity, and the inherent metabolism of different fiber types are critical factors influencing pH decline and pork quality. Further, recent work implicates adenosine monophosphate-activated protein kinase (AMPK) as a major energy sensor for the cell, and thus may be involved in the control of postmortem metabolism. The intent of this paper is to review the biochemistry controlling postmortem energy metabolism in pig muscle and explore new information generated using genetic mutations in order to define the fundamental mechanisms controlling the transformation of muscle to meat. PMID- 22061392 TI - Predictive microbiology: Quantitative science delivering quantifiable benefits to the meat industry and other food industries. AB - Predictive microbiology is considered in the context of the conference theme "chance, innovation and challenge", together with the impact of quantitative approaches on food microbiology, generally. The contents of four prominent texts on predictive microbiology are analysed and the major contributions of two meat microbiologists, Drs. T.A. Roberts and C.O. Gill, to the early development of predictive microbiology are highlighted. These provide a segue into R&D trends in predictive microbiology, including the Refrigeration Index, an example of science based, outcome-focussed food safety regulation. Rapid advances in technologies and systems for application of predictive models are indicated and measures to judge the impact of predictive microbiology are suggested in terms of research outputs and outcomes. The penultimate section considers the future of predictive microbiology and advances that will become possible when data on population responses are combined with data derived from physiological and molecular studies in a systems biology approach. Whilst the emphasis is on science and technology for food safety management, it is suggested that decreases in foodborne illness will also arise from minimising human error by changing the food safety culture. PMID- 22061393 TI - Managing safety and quality through the red meat chain. AB - To successfully manage food safety and quality risks in meat production, a holistic approach is required. The ideal would be a fully integrated assurance system, with effective controls applied at all stages. However, the red meat industry is by nature somewhat fragmented, and a truly integrated system is not at present achievable in all but a few operations. This paper describes a variety of assurance initiatives, and explores how targeted research and development can be used to augment assurance programmes by providing underpinning knowledge, using the Australian beef and lamb industry as an example. PMID- 22061394 TI - Application of genomic technologies to the improvement of meat quality of farm animals. AB - Meat quality is of economic importance in farm animals. It is controlled by multigenes and the environment. During the past few decades, advances in molecular genetics have led to the identification of genes, or markers associated with genes, that affect meat quality. Work on sequencing farm animal genomes will help us to understand how genes function in various organisms and might be applied in the field to study the molecular control of meat quality. Candidate gene and genome scans are two main strategies to identify loci associated with the trait of meat quality. Several genes that influence meat quality have already been, or are close to being, identified. Some of them have been applied to the breeding of farm animals by marker-assisted selection. This will accelerate cumulative and permanent genetic improvement of herds. PMID- 22061395 TI - Identification of pork quality parameters by proteomics. AB - A major parameter for quality of pork is its waterholding capacity (WHC). Prediction of WHC immediately after slaughter would be of benefit both to slaughterhouses for reasons of better logistics and/or branding of premium-meat, and to consumers for improved quality of meat products such as ham. In our pilot study on proteome analysis of porcine muscle by two-dimensional electrophoresis, we have identified at least three and possibly eight significantly changed proteins that may serve as marker proteins for waterholding capacity. The most clearly identified proteins are creatine phospho kinase M-type (CPK), desmin, and a transcription activator (SWI/SNF related matrix-associated actin-dependent regulator of chromatin subfamily A member1, SNF2L1). A possible mechanism of how these proteins may influence WHC is discussed. An optimised protocol for protein extraction that provides for sufficient amounts of relatively pure proteins has been developed. Further studies are needed to validate and extend our preliminary results. PMID- 22061396 TI - Microbial ecosystems of traditional fermented meat products: The importance of indigenous starters. AB - This paper reviews the diversity of microbiota, both in the environment and in traditional fermented European sausages. The environments of processing units were colonised at variable levels by resident spoilage and technological microbiota, with sporadic contamination by pathogenic microbiota. Several critical points were identified such as the machines, the tables and the knives - knowledge crucial for the improvement of cleaning and disinfecting practices. Traditionally fermented sausages generally did not present a sanitary risk. The great diversity of lactic acid bacteria and staphylococci was linked to manufacturing practices. Development of indigenous starters is very promising because it enables sausages to be produced with both high sanitary and sensory qualities. Our increasing knowledge of the genomes of technological bacteria will allow a better understanding of their physiology in sausages. PMID- 22061397 TI - A fresh look at meat flavor. AB - Hundreds of compounds contribute to the flavor and aroma of meat. Complex interactions between various compounds influence the perception of meat flavor. Inherent flavor of a meat product can be influenced by oxidation, lipid content, feeding/diet, myoglobin, and pH. Diet plays an important role in both ruminants and nonruminants. New research reveals important relationships in flavor among multiple muscles within a single animal carcass. This animal effect includes the presence of off-flavors. Diets high in polyunsaturated fatty acids may be contributing to the appearance of off-flavors in beef. Compounds associated with liver-like off-flavor notes in beef have been identified in raw tissue. PMID- 22061398 TI - Technologies to shorten the drying period of dry-cured meat products. AB - Dry-cured meat products are well-known for their unique sensory characteristics. However, the traditional process is very time consuming. The process can be shortened especially by accelerating the drying period, which is the most time consuming. This paper deals with some technological, safety and sensorial aspects for producing fermented sausages and dry-cured hams when the process time is shortened. Different techniques, such as temperature increase and thickness reduction, and the effects of some ingredients and additives are discussed. A Quick-Dry-Slice process based on a continuous system that combines both convective and vacuum drying could accelerate the drying of slices after the desired pH is reached in fermented sausages. There are safety concerns when processes are shortened, but possible additional hurdles, such as the introduction of bacteriocin-producing starter cultures and high-pressure treatments at the end of the process, could reduce them. Methods to speed up the development of typical colour, texture and flavour and their limitations are also discussed. PMID- 22061399 TI - Interventions to reduce/eliminate Escherichia coli O157:H7 in ground beef. AB - The Escherichia coli O157:H7 (E. coli O157:H7) outbreak in the Northwestern United States ushered in an era that has dramatically changed the way beef processors in the United States convert live cattle into meat. Unprecedented cooperation among the beef processors and massive investment in research by the US government and the beef industry have resulted in an acceptable level of control of E. coli O157:H7 in ground beef. The evidence to support the progress in control of E. coli O157:H7 is the CDC data for reduction in human illness as well as the dramatic reduction in the number of E. coli O157:H7-positive samples in USDA-FSIS ground beef monitoring. This manuscript highlights some of the recent findings from our laboratory on the control of E. coli O157:H7 in ground beef. We have also summarized the key events/decisions/milestones that have contributed to the control of E. coli O157:H7 in ground beef in the United States. While there is much to be done to bring E. coli O157:H7 under complete control in the beef sector of the food industry, E. coli O157:H7 also is becoming a major issue in the fresh vegetable sector, as evidenced by the 2006 outbreaks in the United States. We have discussed how the fresh vegetable industry can benefit from the beef industry's experience to expedite the control of E. coli O157:H7 in their products. PMID- 22061400 TI - Application of proteomics to understand the molecular mechanisms behind meat quality. AB - The proteome is expressed from the genome, influenced by environmental and processing conditions, and can be seen as the molecular link between the genome and the functional quality characteristics of the meat. In contrast to traditional biochemical methods where one protein is studied at a time, several hundred proteins can be studied simultaneously. Proteomics is a promising and powerful tool in meat science and this is reflected by the increasing number of studies emerging in the literature using proteomics as the key tool to unleash the molecular mechanisms behind different genetic backgrounds or processing techniques of meat. Thus understanding the variations and different components of the proteome with regard to a certain meat quality or process parameter will lead to knowledge that can be used in optimising the conversion of muscles to meat. At present, there has been focus on development of techniques and mapping of proteomes according to genotypes and muscle types. In the future, focus should be more towards understanding and finding markers for meat quality traits. This review will focus on the methods used in the published proteome analyses of meat, with emphasis on the challenges related to statistical analysis of proteome data, and on the different topics of meat science that are investigated. PMID- 22061401 TI - Tenderness and oxidative stability of post-mortem muscles from mature cows of various ages. AB - Two experiments were conducted to investigate the influence of age of mature cows (2-4yr, 6-8yr, and 10-12yr cows; n=6 in each) on beef quality. In Experiment 1, Longissimus dorsi (LD) steaks were stored at 3 degrees C for 0-10d. Steaks from more mature cows had an increased (P<0.05) Warner-Bratzler shear force (WBSF) and a slower troponin-T post-mortem degradation. Storage reduced WBSF in all steak samples regardless of animal age. In Experiment 2, Semitendinosus (ST) and Semimembranosus (SM) patties were stored at 3 degrees C for 0-7d simulating retail display. The rate of lipid oxidation during storage increased with animal age (P<0.05) and was greater in ST than in SM patties. However, myoglobin oxidation was minimally affected by animal age. Thus, advanced maturation not only intensified cow meat toughness but also lowered its oxidative stability. PMID- 22061402 TI - Biochemical changes during processing of traditional Jinhua ham. AB - Jinhua ham is the most famous traditional meat product of China and one of the most famed dry-cured hams in the world. Its processing consists of six stages: green ham preparation, salting, washing and sun-drying and shaping, ripening, and post-ripening. Intense proteolysis and lipolysis occur during processing period. As a result, the content of free amino acids in final ham products is 14-16 times that of green ham, and 191 volatile compounds have been identified during processing, which make a major contribution to the flavor of Jinhua ham. PMID- 22061403 TI - Effects of metabolic modifiers on carcass traits and meat quality. AB - Much research has been conducted and published about metabolic modifiers that increase growth rate, improve feed efficiency, increase carcass leanness, and decrease carcass fatness. Most of these metabolic modifiers have been developed to improve efficiency and profitability of livestock production and to improve carcass composition, with fewer of them developed and researched specifically to improve meat quality. Some of the metabolic modifiers can have negative effects on visual and sensory meat quality, especially when not used as recommended. This review evaluates the various kinds of metabolic modifiers that have been researched for their effects on production efficiency, carcass composition, and meat quality. Nutritional composition of meat generally is improved from use of most of the metabolic modifiers, visual quality is improved by others, but some can have a negative effect on marbling and tenderness. Anabolic steroid implants are very cost effective and practical for beef cattle production but aggressive implants used within 70 days of slaughter or too frequent use of them will reduce tenderness and marbling. Somatatropin and approved beta-agonists are very effective in improving growth performance and carcass leanness in pigs, and beta agonists are effective in cattle, but improper use of them can have negative effects on marbling and tenderness. Feeding supplemental levels of vitamin E is quite beneficial for improving meat color and shelf-life of beef, lamb, and pork, whereas not supplementing diets with vitamin A has potential for improving marbling in cattle. Immunocastration shows promise for capitalizing on the efficiency of muscle growth of young boars up to a few weeks before slaughter, at which time boar taint is prevented and marbling is improved by immunocastration. Potential exists for improving the fatty acid profile of lipids and increasing conjugated linoleic acid content in beef through dietary manipulation. Supplementing swine diets with conjugated linoleic acid can improve carcass composition of swine, but is not yet cost effective to use. Dietary inclusion of magnesium, manganese, or chromium in diets of pigs and sheep has potential to improve meat color and water-holding capacity. Although, not all of these metabolic modifiers are approved in all countries, proper use of the ones that are approved offers opportunities for economically improving production efficiency and carcass leanness while maintaining acceptable marbling and tenderness, while some provide opportunities to enhance meat color and quality. PMID- 22061404 TI - Cured meat products without direct addition of nitrate or nitrite: what are the issues? AB - The growing popularity of food products marketed in the United States as "natural" and "organic" has resulted in a proliferation of marketing efforts to meet consumer demands for these foods. Because natural and organic foods are not permitted to use chemical preservatives, the traditional curing agents used for cured meats, nitrate and/or nitrite, cannot be added to natural and organic processed meat products. However, alternative processes that utilize ingredients with high nitrate content, such as vegetable-based ingredients, and a nitrate reducing starter culture can produce processed meats with very typical cured meat properties. Because it is not possible to analytically measure the amount of nitrite produced by this process, several potential issues deserve consideration. Regulations, for example, should permit labeling that accurately reflects the process and products, manufacturing procedures must be standardized to achieve product consistency, marketing efforts should clearly communicate the nature of these products to consumers, product quality must be maintained, and microbiological safety must be assured. PMID- 22061405 TI - Temperatures and ages of packs of beef displayed at stores in Canada. AB - The surface temperatures and ages of 1703 retail packs of chilled, raw beef in cut or ground forms on display in a case at each of 41 Canadian retail stores were determined. For each case, data were collected from packs at pre-selected positions in the case. Data for a position were not collected if a pack of beef was not present there. Data were collected at a different time on each of 3 days, with each store being visited within l h after opening and l h before closing and between 12:00 and 14:00 h, without regard to the operation of the case defrosting cycle. The median temperatures of pack surfaces were <4 degrees C, between 4 and 7 degrees C, and >7 degrees C at 24, 16 and one stores, respectively. The maximum temperatures were <4 degrees C, between 4 and 7 degrees C and >7 degrees C at 3, 18, and 20 stores, respectively. The median ages were 0 day, 1 day, and 2 or 3 days at 19, 17 and 5 stores, respectively. The maximum ages were ?2 days, between 2 and 4 days, and >4 days at 21, 14 and six stores, respectively. Temperatures were generally lower at the backs than at the fronts of cases, on upper than on bottom shelves, and within than on the tops of stacks of packs. Temperatures were apparently not affected by the positions of packs along the lengths of cases, and did not differ at different times of day. PMID- 22061406 TI - Metabolic conditions in Porcine longissimus muscle immediately pre-slaughter and its influence on peri- and post mortem energy metabolism. AB - To clarify the physiological prerequisites for the course of energy metabolism post mortem, 80 pigs consisting of four females from each of 20 litters of crossbreeds (Duroc as sireline and Danish Landrace*Danish Large White as dam line) were within litter allocated to four different treatments (A, B, C and D) to provide a large variation in the concentration of the key metabolites glycogen, ATP and creatine phosphate at the time of stunning. (A) no stress before stunning, (B) physical stress consisting of treadmill running (3.8 km/h for 10 min) immediately before stunning, (C) intermediate reduction of glycogen at stunning achieved by application of adrenaline (0.2 mg/kg live weight 15-18 h before stunning), and (D) maximal reduction of glycogen achieved by application of adrenaline (0.3 mg/kg live weight 15-18 h before stunning) and treadmill running (3.8 km/h for 5 min). Compared with resting values (measured in samples taken in the pen the day before slaughter by needle biopsy), longissimus muscle glycogen (16, 13, 57 and 66% for A, B, C and D, respectively), creatine phosphate (17, 22, 12 and 9% for A, B, C and D, respectively) and ATP levels (10, 15, 38 and 31% for A, B, C and D, respectively) measured immediately before stunning were all reduced by the treatments. Stunning caused a rather uniform reduction in creatine phosphate level in all the models. Glycogen concentrations were also further reduced in treatments A, C and D, but not in B, and although ATP levels increased in all the models during stunning, this was only significant for the B model. Consequently, the effect of CO(2) stunning on glycogen and ATP levels depends on pre-slaughter handling. It was also shown that an inverse relationship between ultimate pH and glycogen concentration at the time of stunning existed only when glycogen levels at stunning were below 53 mmol/kg (r=0.88, P<0.001). The validity of this threshold value is discussed. Furthermore, the possibility to standardise the physiological prerequisites of the post mortem pH decreases represents a potent tool to investigate metabolic causes of variations in meat quality characteristics. PMID- 22061407 TI - Role of deoxyhemoglobin in lipid oxidation of washed cod muscle mediated by trout, poultry and beef hemoglobins. AB - Deoxyhemoglobin content was measured in hemoglobins from trout, chicken and bovine sources between pH 5.5 and 7.5. With decreasing pH, deoxyhemoglobin content of trout was highest, low to intermediate in chicken, and lowest in beef hemoglobin. Each type of hemoglobin was added to washed cod muscle and lipid oxidation assessed during 2 degrees C storage. The lipid oxidation rate was trout >> chicken > beef based on thiobarbituric reactive substances (TBARS) and lipid hydroperoxide formation. There was no significant difference in pro oxidative activity of chicken compared to turkey hemoglobin. Hemoglobins from trout appeared to oxidize more rapidly compared to chicken hemoglobin in the washed cod muscle model system, as measured by a decrease in redness (a-value) during storage. Loss of red color was slowest in beef samples. These studies suggest that deoxyhemoglobin may be a major catalyst of lipid oxidation at post mortem pH values found in muscle foods, especially in fish and poultry compared to beef. PMID- 22061408 TI - Novel combinations of chitosan, carnocin and sulphite for the preservation of chilled pork sausages. AB - The aim of this study was to develop novel preservation systems for fresh pork sausages based on combinations of chitosan (polymeric beta-1,4-N acetylglucosamine) carnocin (a bacteriocin produced by Carnobacterium piscicola) and low concentrations of sulphite. Two pilot-scale trials showed that 0.6% chitosan combined with low sulphite (170 ppm) retarded the growth of spoilage organisms more effectively (3-4 log cfu/g) than high levels (340 ppm) of sulphite alone at 4 degrees C for up to 24 days. Microbial counts for frozen sausages showed that the preservative efficacy of the chitosan/sulphite combination was maintained following frozen storage. Carnocin did not protect sausages from spoilage but in a challenge trial, it reduced the numbers of Listeria innocua by up to 2.0 log cfu/g in the first 5 days of chill-storage. Sulphite was degraded rapidly within the first 3 days of storage in all the sausages that contained only this preservative but levels decreased less rapidly and persisted for longer in the presence of chitosan. Results of Quantitative Descriptive Analysis using 31 trained panellists reflected the gradual deterioration of all the sausages during storage. The batch containing chitosan and sulphite deteriorated less rapidly and was judged to be more acceptable for a longer period than all the other batches. PMID- 22061409 TI - Effect of grass or concentrate feeding systems on lamb carcass and meat quality. AB - Thirty-two male Ile de France lambs were divided into four equal groups at age 37 days. Two groups were allowed to graze a natural pasture in France each at a different growth rate (grass high and grass low groups). The other two groups were raised in stalls and fed concentrates to achieve the same growth rates (stall high and stall low groups, respectively) as from the grass groups. The animals were slaughtered when they attained 35 kg and their carcass and meat quality were evaluated. Animals from the two high growth rate groups were slaughtered at an average age of 129 days while those from the low growth rate groups were slaughtered at 163 days. Carcasses from stall-fed lambs were heavier than those from grass-fed lambs as the digestive tract percentage was higher in the grass lambs. Carcasses from stall lambs had better muscular conformation score (P <0.05) and were fattier than those from grass-fed animals. Subcutaneous fat was more yellow and harder in grass-fed lambs (P <0.05). Meat from grass-fed lambs was darker (P <0.05) in colour (lower L*) than meat from stall animals up to 24 h of display. Meat from stall fed animals was more tender and juicier than meat from grass-fed animals (P <0.01), as judged by a trained panel of assessors. Typical lamb flavour was higher in stall-fed lambs (P <0.01). Meat from grass-fed animals had more pronounced liver flavour (P <0.05) and less fatty flavour (P <0.01) than stall-fed lambs. Overall the difference in meat quality between the two different growth rates was minimal. PMID- 22061410 TI - Thermal properties of titin from porcine and bovine muscles. AB - The thermal properties of titin isolated from porcine and bovine longissimus muscles were investigated by differential scanning calorimetry in the temperature range from 20 to 100 degrees C. A single peak with average maximum temperatures of 75.6 and 78.4 degrees C characterized porcine and bovine titin denaturation, respectively. The peaks were much broader than those from the other major muscle proteins. Titin denaturation enthalpy values (1.6-2.6 J/g) were only about half those of whole meat and also lower than those previously determined for myosin, actin, or collagen. The relatively high titin denaturation temperature suggests that it may be partially responsible for meat toughening when muscle tissue is heated above 60 degrees C. PMID- 22061411 TI - Adaptation of microplate reader for measuring oxidative rancidity in meat products. AB - A method to measure 2-thiobarbituric acid reactive substances (TBARS) which was capable of processing large numbers of samples, reducing processing time, and using smaller amounts of reagents was developed. Ground beef, ground pork and ham were analyzed to test the procedure. Acid distillation and aqueous extraction methods for measuring TBARS were adapted for use with a cell culture plate reader (MR5000 Microplate Reader, Dynatech Technologies, Inc., Chantilly, VA) to measure concentration of TBARS. Thiobarbituric acid values obtained by this method are comparable to values obtained by aqueous extraction or distillation procedures using larger quantities of samples and reagents. The method used microliter quantities of reagents and processed a larger quantity of samples than traditional techniques within a shorter time frame. PMID- 22061412 TI - Fermented pork sausage fortified with commercial or hen eggshell calcium lactate. AB - The effects of adding commercial-grade and eggshell calcium lactate on the microbiological and physicochemical properties of Nhams (Thai-style fermented pork sausage) were studied. The Nham calcium levels were 150, 300 and 450 mg/100 g. Compared to controls (no added calcium), calcium fortification did not affect the number of lactic acid bacteria or the colour value. The shear force of Nhams fortified with eggshell calcium lactate decreased (P<0.05) from 32.2 N in the controls to 19.5-22.8 N in Nhams fortified with eggshell calcium lactate. However, Nhams fortified with commercial calcium lactate had the same shear force as the controls. Sensory scores of sour taste, flavour and overall acceptance were not different between the control and calcium-fortified Nhams at a calcium level of 150 mg/100 g. PMID- 22061413 TI - Characterization of proteolysis during the ripening of semi-dry fermented sausages. AB - The respective contribution of indigenous enzymes and enzymes from starter bacteria to proteolysis in fermented sausages were determined by comparing the proteolytic changes occurring in sausages resulting from the presence of a proteolytic strain of Staphylococcus carnosus, i.e. S. carnosus MC 1 to the proteolytic changes occurring in control sausages containing glucono-delta lactone (GDL) and an antibiotic mixture. Proteolysis was quantified by assaying for non-protein nitrogen (NPN) and free amino acids. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and reversed phase high performance liquid chromatography (RP-HPLC) were used to qualitatively assess the proteolytic changes in the sarcoplasmic and myofibrillar proteins as ripening progressed. The concentration of NPN and free amino acids increased in both sausages initially, but subsequently decreased towards the end of ripening in sausages inoculated with the starter culture. SDS-PAGE showed a similar pattern of proteolysis of sarcoplasmic proteins in both sausages, while of the two sausage types; the S. carnosus MC 1 inoculated sausages exhibited the most intense degradation of myofibrillar proteins, especially myosin and actin. RP-HPLC profiles of 2% trichloroacetic acid (TCA)-soluble peptides for the two sausage types were similar, with the production of numerous hydrophilic peptides. N-Terminal amino acid sequence analysis and sequence homology with proteins of known primary structure showed that six of the TCA-soluble peptides were released from the sarcoplasmic (myoglobin and creatine kinase) and myofibrillar (troponin-I, troponin-T and myosin light chain-2) proteins. In addition, the initial degradation of sarcoplasmic proteins was due to the activity of indigenous proteinases, while both indigenous and bacterial enzymes contributed to the initial degradation of myofibrillar proteins. Furthermore, indigenous enzymes were responsible for the release of TCA-soluble peptides, which, were further hydrolysed by bacterial enzymes. PMID- 22061414 TI - Antioxidant effects of rosemary extract and whey powder on the oxidative stability of wiener sausages during 10 months frozen storage. AB - Twelve (Large White*Landrace) gilts were randomly allotted in a 2*2 factorial design with the respective factors being dietary vitamin E (10 or 200 mg/kg feed) and dietary fishmeal (0 or 5%). Wiener sausages were manufactured with or without antioxidants such as rosemary extract and sweet whey powder from meat obtained from the animals after slaughter and stored for 5 days at 4 degrees C. The oxidative stability of the wieners was examined over ten months of frozen storage. Lipid oxidation in the product was measured by means of thiobarbituric acid reactive substances (TBARS) and fluorescence shift. Sensory evaluation of the product to detect oxidative changes was also carried out. The fluorescence shift method was unsatisfactory in the case of wieners containing rosemary extract, as it appeared that the extract contained compounds that fluoresced and therefore interfered with the method. No lipid oxidation as measured by TBARS, fluorescence shift and sensory analysis was observed in wieners stored at -20 degrees C for 10 months. The oxidative stability of wieners was unaffected (P>0.05) by dietary treatments or by the addition of antioxidants. The high oxidative stability of the wieners, even in the absence of antioxidants, could be due to sodium erythorbate present in the formulation as an additional antioxidant. PMID- 22061415 TI - Refractometry of pork muscle and beef connective and adipose tissue. AB - Bulk refractive index (RI) was measured with an Abbe refractometer using a red laser for transmittance (T) and a green laser for reflectance. The critical angle, although obscured by scattering, was detected subjectively at the red green boundary. The refractometer also was operated under computer control, detecting RI photometrically. Pork longissimus thoracis (n=20) had higher RI than biceps femoris (1.357+/-0.004 versus 1.352+/-0.005, respectively, P<0.001). Longissimus thoracis also had lower Japanese pork colour scores (JPCS) than biceps femoris (2.92+/-0.37 versus 3.87+/-0.48, respectively, P<0.001). In pooled samples (n=40), RI was correlated with JPCS, r=-0.55, P<0.001. RI of bovine tendon (n=10) was higher than for adipose tissue (1.415+/-0.009 versus 1.343+/ 0.001, P<0.001). Refraction may contribute to the inverse relationship between meat pH and paleness, and may affect signals from fibre-optic meat probes. PMID- 22061416 TI - Nitric oxide synthase activity in muscle foods. AB - Nitric oxide is enzymatically produced in animals by nitric oxide synthase (NOS). Nitric oxide reacts with superoxide to form peroxynitrite, which initiates oxidative reactions. To assess the potential for nitric oxide formation in muscle, NOS activity was determined in fresh muscle (<8 h post-mortem) from several species under conditions expected in muscle foods. Fresh muscle from all species exhibited NOS activity. NOS activity in muscle was reduced during refrigerated storage. Chicken thigh muscle NOS activity was not affected by pH over the range of 4.5-7.4, but was inhibited by 1 and 2% NaCl. Chicken thigh muscle NOS activity was stimulated at internal cooking temperatures up to 55 degrees C but was completely inhibited at higher temperatures. Results of this study indicate that post-mortem NOS is only active for the first several days of post-mortem storage. PMID- 22061417 TI - Bacteriocinogenic activity from starter cultures used in Spanish meat industry. AB - Thirty-nine bacterial strains, obtained from commercial starter cultures and commonly used by the meat industry in Spain, have been examined for their ability to produce bacteriocins. Fourteen (35%) of them showed antagonism against at least one of the indicator strains, by the agar spot test. The strains showing an inhibitory action against pathogenic indicator strains were identified as Pediococcus acidilactici, Lactobacillus curvatus, Lactobacillus pentosus and Lactobacillus plantarum, which showed an inhibitory action against a wide range of Gram-positive bacteria. The only strain which showed reliable inhibitory activity against pathogenic indicator strains, by the well diffusion assay, was P. acidilactici. This strain produces an inhibitory compound, which reaches its maximum activity at the beginning of the stationary phase of growth. This antimicrobial substance (bacteriocin) has a proteinaceous nature, is stable over a broad range of pH, resistant to heat and shows a bactericidal action. PMID- 22061418 TI - Effects of age on fatty acid composition of the hump and abdomen depot fats of the Arabian camel (Camelus dromedarius). AB - This study aimed to quantify concentrations of fatty acids in the hump and abdomen fats of three different age groups of camel. Hump and abdomen fats were extracted from eight each of one-humped camels (Camelus dromedarius) of three age groups: group 1 (<1 year old), group 2 (1-3 years old) and group 3 (>3 years old). The fatty acid methyl ester concentrations of these fats were determined by gas-liquid chromatography (GLC). The percentage of fat in the hump (H) and abdomen (A) fats was significantly (P<0.05) lower for group 1 (H 92.0% and A 94.3%) than for group 2 (H 97.4% and A 97.2%) and group 3 (H 97.6% and A 97.5%), on a dry matter basis. Hump and abdomen fats from the three different groups had similar fatty acid patterns with more saturated than unsaturated fatty acids. The saturated fatty acids in the hump fats accounted for 58.3, 67.6, and 63.0% of the total fatty acids for groups 1, 2 and 3, respectively; group 1 had significantly (P<0.05) lower saturated and higher unsaturated fatty acid concentrations than group 2. The iodine numbers were significantly (P<0.05) higher in group 1 than either group 2 or 3. Palmitic acid (C16:0) was the major fatty acid in hump fat with 32.06, 32.90 and 34.37%, followed by oleic acid (C18:1) 33.65, 21.66 and 28.91.0% and stearic acid (C18:0) 18.85, 24.13 and 20.74% for groups 1, 2 and 3, respectively. Group 1 had significantly higher (P<0.05) oleic acid and lower stearic acid concentrations than group 2. The melting point of both hump and abdomen fats varied between the age groups. This study indicated that age has an effect on the fatty acid composition and the melting point of hump and abdomen fats in one-humped Arabian camels. PMID- 22061419 TI - Fatty acid composition and quality characteristics of low-fat cooked sausages made with beef and chicken meat, tomato juice and sunflower oil. AB - Low-fat (5.9-10.3% fat) cooked sausages were produced with seven different formulations. Sausages produced with total replacement of fat with sunflower oil had significantly lower oleic acid (C18:1) and higher linoleic (C18:2) and behenic (C22:0) fatty acid contents. Their ratio of TUFA/TS was 3.65 compared to 0.95-1.14 for the other sausages. Also these sausages had the lowest moisture content, highest overall palatability and were less firm. Sausages with tomato juice had the lowest pH value, total aerobic count and nitrite content, but were firmer. Sausages produced with reduced beef contents had lower fat contents, lower stearic (C18:0) and higher oleic (C18:1) fatty acid contents than sausages of high beef content, their texture was very soft and had the lowest score for juiciness. Finally the sausages with chicken meat had the lowest fat and highest salt contents, and lower stearic (C18:0) and higher linoleic (C18:3) fatty acid contents than those made with beef . Also their colour was lighter, less red and more yellow and they had the lowest flavor intensity and overall acceptability. PMID- 22061420 TI - The effect of dietary oregano essential oil on lipid oxidation in raw and cooked chicken during refrigerated storage. AB - The antioxidative effect of dietary supplementation with oregano essential oil on susceptibility of raw and cooked breast and thigh muscle meat of chickens to lipid oxidation during refrigerated storage for 9 days was investigated. Day-old chickens (n=80) were randomly divided into four groups and fed a basal diet containing 30 mg alpha-tocopheryl acetate kg(-1) feed as control, or basal diet plus 200 mg alpha-tocopheryl acetate kg(-1) feed, or basal diet plus 50 or 100 mg oregano essential oil kg(-1) for 38 days prior to slaughter. Lipid oxidation was assessed by monitoring malondialdehyde (MDA) formation in raw and cooked meat during 0, 3, 6 and 9 days of refrigerated storage, using the thiobarbituric acid (TBA) assay and third-order derivative spectrophotometry. Results showed that dietary oregano essential oil supplementation exerted antioxidative effects, the supplementation being most effective in retarding lipid oxidation in stored raw and cooked meat at the 100 mg oregano essential oil kg(-1) feed. However, dietary alpha-tocopheryl acetate supplementation at 200 mg kg(-1) feed displayed greater antioxidant activity than oregano treatments. Thigh muscle was more susceptible to oxidation compared to breast muscle in all treatments, although the former tissues contained alpha-tocopherol at markedly higher levels. PMID- 22061421 TI - Staphylococcus aureus survival, staphylococcal enterotoxin production and shelf stability of country-cured hams manufactured under different processing procedures. AB - Fresh hams were inoculated with Staphylococcus aureus, cured, equalized, cold smoked or non-smoked, and aged. Initial S. aureus populations of 8.57 and 8.12 Log(10) CFU/cm(2) for salt and salt+NO(2)hams decreased to below the levels of detection after the fourth month of aging. S. aureus was detected following enrichment for 75% of the inoculated and 62% of the control hams at the end of the aging period. Staphylococcal enterotoxin was detected in 40% of the inoculated and 50% of the control hams following the aging period. The NaCl content of these hams with or without nitrite were 4.45/3.37% and a(w) values 0.94/0.91. Country-cured ham products obtained from retail stores in Kentucky were all negative for S. aureus enterotoxin. These results indicate that higher salt content and lower a(w) values on country-cured hams play an important role in controlling the growth and toxin production of S. aureus. PMID- 22061422 TI - Single particle tracking of acyl carrier protein (ACP)-tagged TrkA receptors in PC12nnr5 cells. AB - There is a wide interest in studying the membrane mobility of Nerve Growth Factor (NGF) tropomyosin receptor kinase A (TrkA) at the single molecule level, in order to elucidate its diverse signaling responses related to different receptor functions. Here we present an experimental strategy based on the acyl carrier protein (ACP) tag in order to study the dynamics of the high-affinity NGF receptor TrkA in the membrane of PC12nnr5 cells. We present a single-particle tracking (SPT) study using highly photostable semiconductor quantum dots (Qdots) conjugated to ACP-tagged TrkA receptors. We demonstrate that ACP-TrkA shows biochemical and biological properties identical to those of its unmodified counterpart and that single receptor molecules in living cells display distinct diffusive regimes and a highly heterogeneous dynamics. PMID- 22061423 TI - A functional MRI investigation of the association between childhood aerobic fitness and neurocognitive control. AB - We used functional magnetic resonance imaging (fMRI) to examine brain activity of higher fit and lower fit children during early and late task blocks of a cognitive control flanker paradigm. For congruent trials, all children showed increased recruitment of frontal and parietal regions during the early block when the task was unfamiliar, followed by a decrease in activity in the later block. No within-group changes in congruent accuracy were reported across task blocks, despite a decline in performance across all participants, likely due to fatigue. During incongruent trials, only higher fit children maintained accuracy across blocks, coupled with increased prefrontal and parietal recruitment in the early task block and reduced activity in the later block. Lower fit children showed a decline in incongruent accuracy across blocks, and no changes in activation. We suggest that higher fit children are better at activating and adapting neural processes involved in cognitive control to meet and maintain task goals. PMID- 22061424 TI - Synapse formation in adult barrel cortex following naturalistic environmental enrichment. AB - Environmental enrichment paradigms in adult laboratory animals, consisting of physical, perceptual, and social stimulation, have been shown to affect synapse and cell morphology in sensory cortex and enhance learning ability, whereas enrichment, which is in harmony with the animal's natural habitat may have even greater implications for plasticity. Previous studies in our laboratory have shown that whisker stimulation induced the formation of synapses and spines in the corresponding barrel. In the present study adult C57/Bl6J female laboratory mice at 6 weeks of age were placed during 2 months in a protected enrichment enclosure in a forest clearing at the Chisti Les Biological Station, Tvier, Russia. We analyzed neuropil ultrastructure in the C2 barrel using serial-section electron microscopy on a total of eight mice (n=4 enriched, n=4 standard cagemate controls). Quantitative analyses of volumes of neuropil showed a significant increase in excitatory and inhibitory synapses on spines and excitatory synapses on dendritic shafts in the C2 barrel in the enriched group compared with standard cagemate controls. These results demonstrate that naturalistic experience alters the synaptic circuitry in layer IV of the somatosensory cortex, the first cortical relay of sensory information, leaving a lasting trace that may guide subsequent behavior. PMID- 22061425 TI - Early demyelination of primary A-fibers induces a rapid-onset of neuropathic pain in rat. AB - Some types of peripheral neuropathic pain are associated with damage to myelin rather than to axons of primary sensory neurons. It is extremely important to develop selective demyelination animal models for understanding neuropathic pain caused by demyelination. We induced a rapid-onset and reversible demyelination of peripheral A-fibers and neuropathic pain behaviors in adult rats by a single injection of cobra venom into the sciatic nerve. The relation between A-fiber demyelination and the abnormal pain behaviors was investigated using this model. Microfilament recordings revealed that cobra venom selectively blocked A-fibers, but not C-fibers. Selective blockade of A-fibers may result from A-fiber demyelination at the site of venom injection as demonstrated by microscope examination. The axons of the demyelinated A-fibers appeared to be otherwise normal. Neuropathic pain behaviors appeared almost immediately after venom injection and lasted about 3 weeks. Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from both peripheral and central terminals of C-fiber nociceptors. Neurogenic inflammatory responses were also observed in the affected skin via Evan's Blue extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-fiber polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive field. PMID- 22061426 TI - The role of androgens in species recognition and sperm production in Atlantic mollies (Poecilia mexicana). AB - Much is known about the role of hormones in the regulation of vertebrate mating behavior, including receptivity, and several components of mate choice. Hormones may modulate reproductive behavior in such a way to increase or decrease the individual's motivation, and therefore hormones may be important in mediating behavior associated with reproductive isolation. The mating complex of the all female gynogenetic Amazon mollies, Poecilia formosa, and their parental species (sailfin mollies, P. latipinna, and Atlantic mollies, P. mexicana) is a model system for studying ultimate mechanisms of species recognition. However, proximate mechanisms, such as variation in hormone levels, and the effect of hormones on sperm production have not been extensively examined. We predict that one or more of the sex steroid hormones in teleost fish (11-ketotestosterone (KT), testosterone (T), and estradiol (E)) will play a role in species recognition (during mate choice and/or sperm priming) for Atlantic mollies (the maternal parental species) that are sympatric with Amazon mollies. We sequentially paired male Atlantic mollies with female conspecifics and Amazon mollies and obtained water-borne hormone samples before and after mating for all fish. We measured circulating KT, T, and E from the water samples. Although we did not find an overall KT response to mating with conspecifics as has been found previously in sailfin mollies, male Atlantic mollies that mated more with conspecific females had lower postmating T levels. Additionally, males attempted to mate more with conspecific females that had lower postmating E levels, but attempted to mate more with Amazon mollies that had higher postmating KT levels. We also examined the effect of KT on sperm priming (a mechanism of premating mate choice), and found that KT levels of male Atlantic mollies prior to mating are correlated with the sperm priming response when males were paired with conspecific females, but this correlation was not found when males were paired with Amazon mollies. Our results indicate that male mating behavior is affecting or responding to both male and female hormones, but that the hormones alone are not playing a role in species recognition. Male Atlantic mollies may not discriminate against Amazon mollies as strongly as male sailfin mollies because Amazon mollies resemble their maternal parental species more than their paternal species. PMID- 22061427 TI - The HPA axis modulates the CNS melanocortin control of liver triacylglyceride metabolism. AB - The central melanocortin system regulates lipid metabolism in peripheral tissues such as white adipose tissue. Alterations in the activity of sympathetic nerves connecting hypothalamic cells expressing melanocortin 3/4 receptors (MC3/4R) with white adipocytes have been shown to partly mediate these effects. Interestingly, hypothalamic neurons producing corticotropin-releasing hormone and thyrotropin releasing hormone co-express MC4R. Therefore we hypothesized that regulation of hypothalamo-pituitary adrenal (HPA) and hypothalamo-pituitary thyroid (HPT) axes activity by the central melanocortin system could contribute to its control of peripheral lipid metabolism. To test this hypothesis, we chronically infused rats intracerebroventricularly (i.c.v.) either with an MC3/4R antagonist (SHU9119), an MC3/4R agonist (MTII) or saline. Rats had been previously adrenalectomized (ADX) and supplemented daily with 1mg/kg corticosterone (s.c.), thyroidectomized (TDX) and supplemented daily with 10 MUg/kgL-thyroxin (s.c.), or sham operated (SO). Blockade of MC3/4R signaling with SHU9119 increased food intake and body mass, irrespective of gland surgery. The increase in body mass was accompanied by higher epididymal white adipose tissue (eWAT) weight and higher mRNA content of lipogenic enzymes in eWAT. SHU9119 infusion increased triglyceride content in the liver of SO and TDX rats, but not in those of ADX rats. Concomitantly, mRNA expression of lipogenic enzymes in liver was increased in SO and TDX, but not in ADX rats. We conclude that the HPA and HPT axes do not play an essential role in mediating central melanocortinergic effects on white adipose tissue and liver lipid metabolism. However, while basal hepatic lipid metabolism does not depend on a functional HPA axis, the induction of hepatic lipogenesis due to central melanocortin system blockade does require a functional HPA axis. PMID- 22061428 TI - The role of the ventrolateral caudoputamen in predatory hunting. AB - The ventrolateral caudoputamen (VLCP) is well known to participate in the control of orofacial movements and forepaw usage accompanying feeding behavior. Previous studies from our laboratory have shown that insect hunting is associated with a distinct Fos up-regulation in the VLCP at intermediate rostro-caudal levels. Moreover, using the reversible blockade with lidocaine, we have previously suggested that the VLCP implements the stereotyped actions seen during prey capture and handling, and may influence the motivational drive to start attacking the roaches, as well. However, considering that (1) lidocaine suppresses action potentials not only in neurons, but also in fibers-of-passage, rendering the observed behavioral effect not specific to the ventrolateral caudoputamen; (2) the short lidocaine-induced inactivation period had left a relatively narrow window to observe the behavioral changes; and (3) that the restriction stress to inject the drug could have also disturbed hunting behavior, in the present study, we have examined the role of the VLCP in predatory hunting by placing bilateral NMDA lesions three weeks previous to the behavior testing. We were able to confirm that the VLCP serves to implement the stereotyped sequence of actions seen during prey capture and handling, but the study did not confirm its role in influencing the motivational drive to hunt. Together with other studies from our group, the present work serves as an important piece of information that helps to reveal the neural systems underlying predatory hunting. PMID- 22061429 TI - Whole grain rye breakfast - sustained satiety during three weeks of regular consumption. AB - Whole grain rye products have previously been shown to increase feelings of satiety for up to 8h after intake under standardized conditions. This study was set out to investigate the sustainability of the satiating effect after regular consumption of breakfast meals with whole grain rye porridge or refined wheat bread. The study was randomized, cross-over and double-blind. Healthy subjects (n=24) were randomly assigned to daily consumption of iso-caloric standardized breakfast meals with whole grain rye porridge or refined wheat bread for two 3-wk phases, separated by a wash out of 3-4weeks. Each intervention phase had 3 scheduled visit days (days 1, 8 and 22) when appetite ratings (hunger, satiety and desire to eat) were registered for 24h at standardized conditions. Orocecal transit time (salicylazosulfapyridine/sulfapyridine method) and breath hydrogen as an indicator of colonic fermentation were measured at day 8 of each 3-wk phase in a subgroup (n=16). To investigate effects of breakfast on free-living food intake, 3-day weighed food diaries were self-registered during both intervention phases. Whole grain rye porridge breakfast resulted in higher ratings of satiety and lower hunger and desire to eat during 4h post consumption compared to refined wheat bread breakfast (p<0.001). This effect was sustained throughout the 3-wk study phases. Unlike previous studies, the effects did not persist into the afternoon (4-8h). The orocecal transit times after consumption of both breakfasts were similar and in the range of 5-6h. The rye porridge resulted in high levels of breath hydrogen 4-8h after intake, showing extensive colonic fermentation. This was however not related to any changes in appetite during this time-period. There were no significant differences in self-reported macronutrient- and energy intake between diets. This study shows that the satiating effect of rye persists after repeated daily consumption for up to three weeks. Clinicaltrials.gov Identifier: NCT01117363. PMID- 22061430 TI - The effect of chewing gum on physiological and self-rated measures of alertness and daytime sleepiness. AB - The proposition that chewing gum can improve alertness was investigated via both physiological and self-rated measures. The Pupillographic Sleepiness Test (PST) provided a measure of pupillary unrest (PUI); a physiological index of daytime sleepiness. Chewing gum reduced the extent of sleepiness as measured by both PUI and self-rated sleepiness. Specifically, in comparison with sham chewing and no chewing controls, the chewing gum condition significantly limited the increase in pupillary unrest following the 11-minute PST within a darkened laboratory: a finding indicating moderation of the daytime sleepiness increase for the chewing gum condition. In addition, there was some evidence that chewing gum (relative to the no-chewing condition only) moderated the increase in a self-rated measure of sleepiness (Stanford Sleepiness Scale). However, there was no evidence that chewing gum moderated the decrease in self-rated alertness (Bond-Lader Visual Analogue Mood Scale). Although the precise mechanism underpinning the effect of chewing gum is unclear, the reduction in daytime sleepiness may be underpinned via heightened cerebral activity following the chewing of gum or the arousing effects of mint flavour. PMID- 22061432 TI - Editorial. PMID- 22061431 TI - Introducing personalised care planning into Newham: outcomes of a pilot project. AB - AIM: To explore the feasibility and acceptability of implementing a personalised care planning approach for diabetes care in general practice. METHODS: A four stage care planning process was introduced for diabetes annual review, involving patients (1) being made aware of the new process, (2) attending an appointment to gather clinical data, (3) receiving and reviewing their results and (4) attending a care planning consultation. The latter is a collaborative discussion with the health professional about their response to their results, their goals and desired action plan. Health professionals received specialist training in personalised care planning, including practice observations and feedback. RESULTS: Sixty-six per cent of patients eligible to participate in the project attended both appointments and received an annual review. Of these, 89% also agreed a personalised care plan. Staff reported greater engagement among patients who had read and understood their results. Fourteen per cent of patients reported that they had not agreed a care plan but would have liked one. Patients reported increased confidence in managing their condition with 75% feeling that their ideas and goals were discussed completely. CONCLUSIONS: Introducing personalised care planning to general practice diabetes care is possible and well received. Our model for implementation of personalised care planning, which includes specialist training for practice teams and ongoing support from local colleagues and health organizations, can help to meet national recommendations for the provision of personalised care plans for people with long-term conditions. When implementing personalised care planning, efficient administration is vital and behaviour change is necessary for both staff and patients. PMID- 22061433 TI - Assay of Cathepsin D activity in fresh pork muscle and dry-cured ham. AB - Different assays of cathepsin D activity in both porcine muscle and dry-cured ham extracts have been tested in order to find the best conditions for a reliable detection of cathepsin D in dry-cured meat products. The enzyme was effectively extracted with 0.2% (v/v) of Triton X-100. Nucleases if present were not observed to interfere with the assays. The best conditions for a reliable detection of cathepsin D in dry-cured ham were found to be the incubation of the enzyme extract for 1 h at 45 degrees C in a reaction mixture containing 0.60% (w/v) of haemoglobin in 0.2 m sodium citrate buffer, pH = 3.7. PMID- 22061434 TI - Fatty acid composition of lipid in Longissimus dorsi muscle of Duroc and British Landrace pigs and its relationship with eating quality. AB - The fatty acid composition of intramuscular fat from Duroc and halothane negative British Landrace pigs was determined and the relationships between fatty acid concentrations and aspects of eating quality were estimated from data on 160 pigs. Boars and gilts from each breed were performance tested on ad libitum or restricted feeding regimes with an average slaughter weight of 80 kg. Eating quality was assessed by ten experienced taste panelists. Intramuscular fat of Duroc pigs had higher concentrations of saturated and mono-unsaturated fatty acids and lower concentrations of poly-unsaturated fatty acids than Landrace pigs. With increasing intramuscular fat content, concentrations of saturated and mono-unsaturated fatty acids increased and concentrations of poly-unsaturated fatty acids decreased and the rate of change in fatty acid concentrations was greater in Landrace pigs than in Duroc pigs. Eating quality traits were generally improved as the concentration of mono-unsaturated fatty acids increased and poly unsaturated fatty acids decreased. PMID- 22061435 TI - Preservative effect of combinations of acetic acid with lactic or propionic acid on buffalo meat stored at refrigeration temperature. AB - A silverside of buffalo was cut in 15 equal-sized steaks and divided into five groups, each group containing three steaks. The steaks from groups 1,2,3 and 4 were treated with 1, 2, 3 and 4% acetic:lactic acid combinations, respectively, and the fifth group was kept as a control. Similar treatments were also given with acetic: propionic acid mixtures. The microbial analysis and changes in colour and odour were noted at 0, 24, 72 and 168 h. The bacteriostatic and bacteriocidal action of the acid mixtures increased with increasing concentration but the effect was reduced as the time advanced. Both acid mixtures had pronounced antibacterial effect on gram negative organisms than gram positive ones. The 3% acetic: lactic acid combination showed reduction in bacterial numbers without affecting the colour and odour of buffalo meat and is recommended for decontamination and preservation of meat for up to seven days at refrigeration temperature (7 +/- 1 degrees C). PMID- 22061436 TI - Stunning and shackling influences on quality of porcine Longissimus dorsi and Semimembranosus muscles. AB - Seventy-one barrows of three porcine genotypes (nn, Nn and NN genotypes with respect to halothane) were electrically stunned on the right side and randomly assigned to one of three treatments during the bleeding process (prone, PR; shackled left, SL; or shackled right, SR) to investigate the influence of both shackling and stunning on ultimate meat quality. PR carcasses had less side-to side variation in 40 min pH than either SL or SR carcasses. Shackling contributed to a decreased 40 min pH in the semimembranosus (SM) and posterior longissimus dorsi (PL). The effects of stunning appeared to be additive when combined with shackling, tending to lower pH in the mid-longissimus dorsi (ML; P <- 0.10). The 'free' side of the shackled carcass also had significantly lower 40 min pH in the ML, PL and SM locations when compared to PR sides. Genotype had no influence on shackling since there was no treatment by genotype interactions. Despite significant effects on post-mortem metabolism (indicated by the differences in 40 min pH) shackling alone had little influence on overall ultimate meat quality of the carcass. Depending on the sampling location, soluble protein and L (*) and b (*) values varied among treatments. Shear force and a (*) values were similar among treatments, but PR and SL carcasses had significantly lower expressible juice and drip loss compared to SR carcasses. These results suggest that, although shackling alone has little effect on meat quality, in combination with electrical stunning, shackling can lead to a decrease in meat quality. PMID- 22061437 TI - Kinetics of hydration properties of meat emulsions containing various fillers during smokehouse cooking. AB - The cooking kinetics of meat emulsions containing various fillers was determined by monitoring changes in hydration properties such as cooking loss and water holding capacity during smokehouse cooking. Press juice, consumer cook test and emulsion stability of cooked product were also determined. The fillers used were buttermilk powder, corn starch, microcrystalline cellulose, modified corn starch, modified wheat flour, soy-protein concentrate and whey-protein concentrate. The cooking process was modelled using reaction kinetics and Eyring's absolute reaction rate theory. Enthalpy and entropy changes of activation were calculated for various properties and fillers. PMID- 22061438 TI - Kinetics of pH and colour of meat emulsions containing various fillers during smokehouse cooking. AB - The cooking kinetics of meat emulsions containing various fillers was determined by monitoring changes in pH and colour during smokehouse cooking. The fillers used were buttermilk powder, corn starch, microcrystallline cellulose, modified corn starch, modified wheat flour, soy-protein concentrate and whey-protein concentrate. The cooking process was modelled using reaction kinetics and Eyring's absolute reaction rate theory. Enthalpy and entropy changes of activation were calculated for various properties and fillers. PMID- 22061439 TI - Dietary energy and protein effects on partitioning of carcass components in beef cattle. AB - This study evaluated carcass and wholesale cut composition of 20 Angus steers fed two levels of protein (LP = 8% versus HP = 14%) at two levels of energy intake (LE = 1.96 versus HE = 2.67 Mcal ME) at 6.35 kg head(-1) d(-1) dry matter intake for 238 d using a factorial arrangement (n = 5/diet). The left side of each carcass was physically separated into wholesale cuts and each cut was, in turn, physically separated into the lean, subcutaneous fat, intermuscular fat, bone portions and cavity fat when applicable. Intramuscular fat for the entire side was chemically determined using only the separated lean tissue component. Energy was the greatest source of variation (P < 0.05) on carcass and wholesale cut composition: HE was associated with more total carcass fat (32.4 versus 23.9%) and less lean (56.7 versus 60.2%) and bone (17.9 versus 20.1%) than LE. Protein by energy level interactions (P < 0.05) were observed for carcass subcutaneous fat and carcass lean in addition to brisket subcutaneous fat, round subcutaneous fat and bone. The HP:HE group had the least carcass lean and the most subcutaneous fat followed by the LP:HE group, LP:LE and then HP:LE. This was also the trend for the wholesale cut composition. These results suggest that fat deposition in cattle can be significantly and favorably reduced in wholesale cuts by adjusting the relative balance of dietary protein and energy. PMID- 22061440 TI - Microbial quality, and effect of cooking on survival of Salmonella, in Kokaric. AB - A special preparation from the small intestine of lamb, called kokaric, is widely consumed in Turkey. In this study, Salmonella was not isolated from raw kokaric. Conventional ways of cooking, except precooking, destroyed Salmonella in artificially contaminated kokaric. The microbial quality of cooked kokaric bought from street sellers was not safe for public health consumption because of environmental contamination. PMID- 22061441 TI - Superb fluoride and arsenic removal performance of highly ordered mesoporous aluminas. AB - Highly ordered mesoporous aluminas and calcium-doped aluminas were synthesized through a facile and reproducible method. Their fluoride adsorption characteristics, including adsorption isotherms, adsorption kinetics, the effect of pH and co-existing anions were investigated. These materials exhibited strong affinity to fluoride ions and extremely high defluoridation capacities. The highest defluoridation capacity value reached 450 mg/g. These materials also showed superb arsenic removal ability. 1g of mesoporous alumina was able to treat 200 kg of arsenic contaminated water with a pH value of 7, reducing the concentration of arsenate from 100 ppb to 1 ppb. PMID- 22061442 TI - Size distributions and exposure concentrations of nanoparticles associated with the emissions of oil mists from fastener manufacturing processes. AB - The aims of the present study were set out to measure size distributions and estimate workers' exposure concentrations of oil mist nanoparticles in three selected workplaces of the forming, threading, and heat treating areas in a fastener manufacturing plant by using a modified electrical aerosol detector (MEAD). The results were further compared with those simultaneously obtained from a nanoparticle surface area monitor (NSAM) and a scanning mobility particle sizer (SMPS) for the validation purpose. Results show that oil mist nanoparticles in the three selected process areas were formed mainly through the evaporation and condensation processes. The measured size distributions of nanoparticles were consistently in the form of uni-modal. The estimated fraction of nanoparticles deposited on the alveolar (AV) region was consistently much higher than that on the head airway (HD) and tracheobronchial (TB) regions in both number and surface area concentration bases. However, a significant difference was found in the estimated fraction of nanoparticles deposited on each individual region while different exposure metrics were used. Comparable results were found between results obtained from both NSAM and MEAD. After normalization, no significant difference can be found between the results obtained from SMPS and MEAD. It is concluded that the obtained MEAD results are suitable for assessing oil mist nanoparticle exposures. PMID- 22061443 TI - Boroaluminosilicate glasses: novel sorbents for separation of Th and U. AB - Boroaluminosilicate glass having a specific composition could be successfully used for the selective uptake of thorium from a mixture containing uranium by controlling the solution pH only. Single ion uptake studies showed that the uptake of uranium and thorium was maximum at pH of 4.5 and 7.5, respectively. But uptake studies using mixtures with uranium and thorium showed that irrespective of the pH, the uptake of thorium was higher than that of uranium. PMID- 22061444 TI - Extractive fermentation for improved production and recovery of lipase derived from Burkholderia cepacia using a thermoseparating polymer in aqueous two-phase systems. AB - An extractive fermentation technique was developed using a thermoseparating reagent to form a two-phase system for simultaneous cell cultivation and downstream processing of extracellular Burkholderia cepacia lipase. A 10% (w/w) solution of ethylene oxide-propylene oxide (EOPO) with a molecular mass of 3900 g/mol and pH 8.5, a 200 rpm speed, and 30 degrees C were selected as the optimal conditions for lipase production (55 U/ml). Repetitive batch fermentation was performed by continuous replacement of the top phase every 24h, which resulted in an average cell growth mass of 4.7 g/L for 10 extractive batches over 240 h. In scaling-up the process, a bench-scale bioreactor was tested under the conditions that had been optimized in flasks. The production rate and recovery yield were higher in the bioreactor compared to fermentation performed in flasks. PMID- 22061445 TI - Cloning of the cDNA, localization, and physiological effects of FGLamide-related allatostatins in the blood-gorging bug, Rhodnius prolixus. AB - Allatostatins (ASTs) are insect neuropeptides that were first identified as inhibitors of juvenile hormone biosynthesis by the corpora allata. There are three families of ASTs in insects, defined by their C-terminus conserved regions, one of which is FGLamide. Here we determine, for the first time in a hemipteran, the complete 1013 bp cDNA sequence encoding the Rhodnius prolixus FGLa/ASTs (Rhopr-FGLa/ASTs), and confirm the transcript size using northern blot. Phylogenetic analysis suggests that the Rhopr-FGLa/AST prepropeptide is most similar to the FGLa/AST precursors identified in Hymenoptera. Reverse transcriptase PCR demonstrates that the Rhopr-FGLa/AST transcript is highly expressed in the central nervous system (CNS) in unfed fifth-instar R. prolixus, and is reduced in expression in CNS dissected from one day old blood-fed insects. Fluorescent in situ hybridization shows transcript expression in neurons in each ganglion of the CNS, but also in cells located on peripheral nerves. Rhopr FGLa/ASTs dose-dependently inhibit contractions of the anterior midgut and hindgut, suggesting a role in feeding-related physiological events. PMID- 22061446 TI - Performance of longitudinal and volumetric tube current modulation in a 64-slice CT with different choices of acquisition and reconstruction parameters. AB - Aim of the study was to evaluate the performance of a tube current modulation (TCM) system ((SURE)Exposure 3D). On a 64 detector-row CT scanner (Aquilion 64, Toshiba), performance of fixed tube current, longitudinal TCM, and volumetric TCM acquisitions were assessed. A homogeneous cone-shaped phantom and an anthropomorphic phantom were used. Tube current and noise profiles were quantitatively analysed by box and whisker plots when phantom size, acquisition, and reconstruction parameters were varied. At similar median noise, fixed tube current scanning showed a noise range of 16.8-38.3 HU, while longitudinal TCM showed a range of 19.4-31.4 HU and volumetric TCM showed an even lower range of 20.7-28.7 HU. When acquisitions resulting in similar image quality (noise) were compared, the use of volumetric compared to longitudinal TCM resulted in a variable radiation dose reduction up to 6.6%. In conclusion, (SURE)Exposure 3D resulted in more uniform image quality at a lower dose. Volumetric TCM shows improved results over longitudinal TCM. PMID- 22061447 TI - 38th international congress of meat science & technology August 1992, Clermont Ferrand, France. PMID- 22061448 TI - Consumer demands: Major problems facing industry in a consumer-driven society. AB - Demand is driven by conventional market forces over much of the world among consumers with strong positive attitudes to meat as a nutritious, tasty and premium food; price in relation to income, availability, quality (including leanness) and relevance to life-style remain the dominant forces operating. But in the developed world, there are emerging concerns about how meat is produced, which are likely to have negative effects on demand, particularly that of the current younger generation, and which may well begin to affect Government policies towards the meat industry. The industry needs to establish strong information and education programmes, but also to examine its procedures to provide greater consumer assurance about practises and controls. Also the scientists and technologists serving the industry need to help it move towards sustainable lower input, less environmentally damaging systems, less reliance on drugs, stimulants and additives, sensitive exploitation of the new genetics and with more consideration for the animals involved. PMID- 22061449 TI - What do we need for a value-based beef marketing system? AB - A functioning value-based marketing system is critical to the economic well-being of the beef industry. Producers must be paid for producing what the consumers demand. Clear signals must come from the consumer to the marketing chain to the producer. The US beef industry has agreed upon eight consensus points that need to the resolved before a functioning value-based marketing system can become a reality. Following the agreement on these consensus points, the US beef industry has declared 'War on Fat'. The consensus points and the industry's 'war' plans are discussed. PMID- 22061450 TI - The future role of molecular genetics in the control of meat production and meat quality. AB - Current applications of quantitative genetics for genetic improvement of farm animals rely on sophisticated statistical procedures applied to failly simple genetic models and have been effective in producing large cumulative genetic changes in many traits. Recent advances in molecular genetics provide a potential for renewed methods in animal breeding. The two main possible fields of application of recombinant DNA methologies, i.e. marker-assisted breeding and gene transfer, are reviewed. Use of genetic markers as an aid to present breeding practice appears to be rather promising, but research effort remains to be done before implementation of marker-assisted breeding schemes on a significant scale. It is not, at this stage, obvious that transgenesis will be an important way of improving meat-producing animals, at least in the near future. PMID- 22061451 TI - Preslaughter handling, stunning and slaughter. AB - This paper reviews some of the recent developments in scientific research into preslaughter handling, transport, stunning and slaughter. Particular emphasis has been placed on work published within the past 2 years, and on the welfare and meat quality aspects of the subject. PMID- 22061452 TI - Consumer attitudes to meat eating. AB - This study reports on current meat consumption in the UK and the factors that are percieved by the subjects to be influential in their choice of diet. A random sample of individuals from the population (n-1018) were questioned on their consumption and attitudes towards meat by a postal survey. The study revealed that 28.3% of the population considered themselves to be reducing meat consumption; attitudes found to be determinant in changes in the consumption of meat were healthiness, taste and concerns over additives. Hypothetical future events were found to affect people's estimated meat-eating. Knowledge of meat related information was investigated with specific reference to the respondents' trust in the various sources used; food package labels were found to be an influential source of meat-related information. PMID- 22061453 TI - Sensory properties and preferences. AB - Common mistakes are frequent in sensory evaluation of meats and meat products. Conceptual confusion is often observed in triangular tests when add-on questions are included in the testing procedures, and when descriptive and hedonic scales are mixed in profiling exercises. Similar consumer responses are often recorded from trained, and thus biased, panels. Preference for meats seems to be most strongly affected by changes in colour/appearance and texture, and to a lesser extent by changes in flavour (that is when off-flavours are not present). It is difficult to generalise as to whether appearance/colour attributes or texture attributes are the most important. A simplified model for texture understanding is suggested, where water/fat perception and structure perception (described by juiciness and tenderness) are orthogonal phenomena and where most other textural attributes can be explained by this structure. PMID- 22061454 TI - The flexibility of the collagen compartment of muscle. AB - Collagen, the major connective tissue protein, is an integral constituent of muscle and, because of its occurrence and characteristics, is a factor contributing to the texture of meat. This brief review focuses on aspects of collagen biosynthesis and experimental data which indicate the collagens of muscle possess remarkable capacity for change. Over 90% of the intramuscular collagen of meat is located in the perimysium. This fibrillar collagen is comprised predominantly of two collagen phenotypes, types I and III, whose proportions vary with animal age, muscle type, gender and probably rate of collagen synthesis. Collagen in muscle can differ additionally in crosslinking profile. Collagen crosslinks are structures arising from the condensation of lysine or hydroxylysine residues and their aldehydes. Crosslinks link two or three collagen molecules or (collagen fibrils) together. Both the tensile strength of collagen and the toughening of meat due to its connective component are related to collagen crosslink type and concentration. With age and maturation there is a general and progressive shift in collagen type (toward more type I) and an increase in the concentration of mature crosslinks. Such alterations in collagen characteristics, rather than significant changes in collagen concentrations, are responsible for the toughening of meat as animals age. Data also suggest that management practices which alter growth and muscle accretion rates can have a profound affect on collagen characteristics. Increasing or decreasing plane of nutrition, compensatory growth, testosterone- and somatotropin-mediated growth, and exercise alter collagen crosslink and/or type proportionally. Such changes can sometimes be associated with increased shear force scores for cooked meat. Alterations in muscle collagen characteristics are linked directly or indirectly to perturbations in collagen synthesis and turnover rates accompanying growth and muscle accretion. The concept that collagen does not change once deposited extracellularly or that changes in its characteristics are unidirectional does not appear to be valid in muscle tissues. Rather collagen appears to be a very flexible component of the extracellular matrix. Potential for management practices to alter collagen characteristics therefore exists. PMID- 22061455 TI - Muscle proteinases and meat aging. AB - The purpose of this manuscript is to review and summarize the results of experiments conducted in our laboratory regarding the mechanism of meat tenderization during post mortem storage of carcasses at refrigerated temperatures. Clearly, the conversion of muscle to meat and the subsequent tenderization process are complex phenomena and much remains to be learned. However, current experimental data suggest that proteolysis of key myofibrillar proteins is the principal reason for improvement in meat tenderness during post mortem storage. Speculatively, the weakening and/or degradation of Z-disks and degradation of desmin (and probably degradation of titin) are responsible for the increased fragility of myofibrils during post mortem storage. There is substantial experimental evidence suggesting that the calpain proteolytic system is resposible for post mortem proteolysis that results in meat tenderization. Calpain is the only proteolytic system that has all of the characteristics that are necessary for bringing about post mortem changes that result in meat tenderization. Undoubtedly, other factors (such as rate pH and temperature decline during rigor development, ionic strength and others) influence the process. However, we believe that the rate and extent of post mortem proteolysis best explain the observed variation in tenderness at a constant age. Therefore, research efforts should be direct toward understanding the regulation of the calpain proteolytic system in post mortem muscle. PMID- 22061456 TI - Optimisation of tenderisation, ageing and tenderness. AB - Tenderness is an important part of meat acceptability and is affected by variations in production and processing. The tenderisation process was modelled on the activity of calpain proteinases. The extent of tenderisation is proportional to the level of calpains which accounts for the toughness of meat from beta-adrenergic agonists. The rate of tenderisation increases with higher temperature and faster rigor development. These are responsible for the faster tenderisation in chicken, in meats following the use of electrical stimulation and in meats of high ultimate pH. Knowledge of these mechanisms of tenderisation afforded processes for optimisation of tenderness. PMID- 22061457 TI - Impact of animal husbandry and slaughter technologies on microbial contamination of meat: Monitoring and control. AB - The microbial flora transferred to carcasses during slaughter is a reflection of the care taken on the slaughter floor and of the types and numbers of microorganisms acquired by the animal on the farm or during the period of transportation to the slaughter house. These microogranisms may include those able to cause illness in the consumer, or microorganisms responsible for spoilage of the product. Considerable progress has been made in reducing contamination at slaughter and thereby extending the shelf-life of meat. In contrast, international statistics still clearly show that meat and meat products are responsible for a major proportion of all foodborne infections. This latter aspect is not determined by the overall number of microorganisms present but by the bacterial composition of the animal's gut flora at slaughter. Preventive quality assurance along the whole productions and processing line is therefore the only effective means of controlling the microbiological safety and quality of meat. This includes hazard analysis techniques to identify critical control points and procedures for monitoring the microbiological status of both animals and carcasses since most of the critical points cannot be totally controlled. At early stages in the production line, colonisation of meat animals with pathogens should be prevented. Subsequently, good slaughter practices will ensure carcasses of good overall microbiological quality. This paper deals with microbiological monitoring systems that can be used at different stages of production and processing to control the microbiological quality of poultry and pig meat. PMID- 22061458 TI - Starters in the processing of meat products. AB - Starter cultures applied in meat technology may contain moulds, yeasts and bacteria. Moulds have been selected with the primary intension to exclude any potential of mycotoxin production. Their sensory effects and the requirements of technology are also criteria for suitable starters. Their genetic potential can now be modified by genetic engineering. Yeasts are applied for sensory reasons mainly. The species in use are only fermentative and do not enhance nitrate reduction. Bacterial components of starters consist of micrococci, staphylococci, lactic acid bacteria (LAB) and, with minor importance, Streptomyces griseus or Aeromonas sp. For selection of the appropriate organisms and for ensuring optimum performance in the fermentation process, their technological, ecological, physiological and genetic properties should be well known. Most knowledge is available for LAB, which represent the most important group of starter organisms, since they are involve in the fermentation of all types of products and contribute to each single aim of the fermentation process. The study of the properties of the organisms may also contribute to reduction of potential hygienic risks not only in the classical fields of starter application but also in new fields where they may be employed as protective cultures that inhibit the growth of food pathogens or even spoilage organisms. Strains with an improved potential to reduce these risks and to exhibit further useful properties can be obtained by means of genetic engineering. Examples for successfully modified meat specific bacteria are Staphylococcus carnosus and lactobacilli L. curvatus and L. sake. PMID- 22061459 TI - Oxidative processes in meat and meat products: Quality implications. AB - Lipid peroxidation is, in most instances, a free radical chain reaction that can be described in terms of initiation, propagation, branching and termination processes. With regard to lipid peroxidation, one of the most important questions concerns the source of the primary catalysts that initiate peroxidation in situ in muscle foods. When cells are injured, such as in muscle foods after slaughtering, lipid peroxidation is favored, and traces of O(2) and H(2)O(2), indicating lipid peroxides, are formed. The stability of a muscle food product will depend on the 'tone' of these peroxides and especially from the involvement of metal ions in the process. The cytosol contains not only prooxidants but also antioxidants and the tone of both affects the overall oxidation. Lipid peroxidation is one of the primary mechanisms of quality deterioration in foods and especially in meat products. The changes in quality can be manifested by deterioration in flavor, color, texture, nutritive value and the production of toxic compounds. PMID- 22061460 TI - Objective measurements of carcass and meat quality. AB - Lost competitiveness and declining per capita consumption have forced US meat industry sectors to become consumer oriented and address issues related to quality shortfalls. Because industry goals for value and quality-based marketing are becoming a reality, interest in objective carcass evaluation methodology has escalated. Even so, no official instrument grading systems are in place. Research addressing use of A-mode, B-mode and real-time ultrasound technique indicated several distinct advantages: (1) it may be used in live animals; (2) it may be used on slaughter floors before hide removal; (3) with development, it may accurately predict traits related to palatability; (4) it offers no health hazards; (5) it would allow complete automation of grading and remove the element of human error; and (6) with development, it offers great compatability with integrated artificial neural networking technology. However, other systems are now available which may present alternatives. Electrical conductivity (TOBEC) effectively predicts pork carcass composition, and is now used commercially. Potential exists for similar systems in the beef industry. Other instruments (NMR, CAT, PET), with continued development, offer advantages in image resolution and accuracy, but are cost prohibitive at this time. Elastography, a new technique, offers exciting prospects for the future with its potential to predict tenderness. PMID- 22061461 TI - Mechanical properties of meat. AB - Determination of meat mechanical properties is still usually performed under empirical conditions, using tests which have been developed many years ago. This paper discusses the limitations of these methods. It also reviews recently developed research which has been focused on a more analytical approach to mechanical tests performed in closely controlled conditions. The objectives of these investigations are on the one hand to obtain specific properties of the myofibre and connective tissue structures involved in meat toughness and on the other hand to understand the fracture mechanisms involved in the perception of texture. Due to the anisotropic and composite nature of meat, attention has been focused on the influence of the direction and amplitude of strains to be used for the characterisation of myofibres and connective tissue, respectively. These strain conditions are linked to the contraction and stretching state of each of these structures. Indeed, whatever the type of deformation (shear, compression or tension), myofibre resistance can be determined under low strain conditions as long as collagen fibres in the connective tissue remain in a more crimped state than myofibres, i.e. in raw or slightly cooked meat of normal sarcomere length. On the contrary, determination of connective tissue resistance has, up to now, only been obtained using large strain tests. Contraction of collagen fibres induced by cooking makes the separate analysis of meat structures more difficult, but this can partially be overcome by applying mechanical tests in different strain directions. However, the role of the spatial distribution of connective network on the mechanical properties of meat still remains largely unknown. Image analysis and ultrasonic methods, currently developed to study this problem, are briefly presented. PMID- 22061462 TI - Elastography of beef muscle. AB - Elastography, a technique that uses ultrasonic pulses to track the internal displacements of small tissue elements in response to an externally applied stress, has been applied to beef muscle. Beef longissimus (1 day post mortem) and semimembranosus (5 days post mortem) muscles were obtained from A maturity beef carcasses. Samples were vacuum-packaged and frozen to -20 degrees C. For elastography measurements, muscles were equilibrated to a constant temperature (30 degrees C+/- 0.5) in a water tank. Custom transmitters and receivers were used in conjunction with a 2.25 MHz medical transducer. The transducer was driven by a 286 PC, and the radio-frequency echoes digitized at 50 MHz and 8 bits. The pre- and post- compression echo trains (A-lines) were subjected to cross correlation analysis. Visual interpretation of beef elastograms demonstrate circular areas of relatively inelastic tissues and smaller, banding areas of elastic tissues in the cross-section of beef longissimus muscle. The dark inelastic areas from the elastograms may be related to myofibrilar areas from the same muscle sections; the light, elastic band areas from the elastograms may be related to perimysiaal connective tissue or intramuscular fat. Fatty septa and a calcified abscess could be easily identified on the elastogram. These preliminary results demonstrate that elastography may have potential as a non-intrusive method of visualizing tissue components of beef muscle. PMID- 22061463 TI - Physical measurements of meat quality: optical measurements, pros and cons. AB - This review describes recent progress in understanding the optical properties of meat and considers how optical properties of meat might be used for quality control in the meat industry. The birefringence of myofibrils changes with pH so that, as the pH decreases towards the isoelectric point, the optical path difference increases. Thus, transmittance through muscle fibres is decreased and scattering of light in meat is increased. New ways have been found to monitor pH related paleness by measuring the light scattered at different wavelengths and angles through the meat. A prove for the optical detection of subcutaneous fat depth in carcasses has been modified so that now it detects the distribution of collagen. UV light is reflected from a dichroic mirror into an optical fibre in the probe, andnd the fluorescence of connective tissue passing by the optical fibre is detected. Although these and other methods for the optical measurement of various aspects of meat quality are technically very promising, there are formidable problems to be overcome in developing a commercial application. A major industrial commitment to measuring meat quality in individual carcasses is required, together with a willingness to invest in the development of new technology. PMID- 22061464 TI - Low-fat meat products-technological problems with processing. AB - Diet and health advice serve as a driving force to redirect the types of foods considered to be most beneficial in terms of improved health and quality of life for Americans. Although meat cuts have become leaner, products such as ground beef, fresh pork sausage, coarse ground sausages and emulsified sausages traditionally have higher levels of fat. However, these products offer the greatest opportunity for fat reduction by reformulation with fat substitutes. Fat replacements should contribute a minimum of calories to a product and should not be detrimental to organoleptic qualities. Most substitutes can be categorized as: leaner meats, added water, protein-based substitutes, carbohydrate-based substitutes and synthetic compounds, Reducing the fat content to ~10% often results in cooked ground beef that is bland and dry with a hard, rubbery or mealy texture. Reformulation with fat substitutes can cause a reduction in particle binding, darker product color, lack of beef flavor, reduced browning reactions and shorter microbiological shelf-life. Other problems that occur with low-fat (5 10%) fresh or cooked/smoked sausages are reduced cook yields, soft mushy interiors, rubbery skin formation, excessive purge in vacuum packages, shorter shelf-life and changes in sensory qualities after cooking or reheating. However, some combinations of fat replacements that mimic the mouthfeel and textural characteristics of fat offer potential for development of low-fat meat products. PMID- 22061465 TI - Advanced technologies in the meat industry. AB - New Zealand has invested heavily in the development of slaughter dressing and deboning equipment and machinery for sheep and lamb. In total some thirteen machines have been developed to date and all are now commercially available and many examples are working within New Zealand and overseas. Significant economic savings have been derived from the introduction of these machines. The Australian meat industry is funding a major programme in beef slaughter technology development. Eleven modules have been developed and at present they are being incorporated into a commercial plant at Kilcoy in Queensland, Australia. The Netherlands have a programme named Slaughterline 2000 which includes a number of pork slaughtering and processing initiations. Stunning, sticking and an automatic carcass opener are developments within this programme. PMID- 22061466 TI - Effects of fat level, oat fibre and carrageenan on frankfurters formulated with 5, 12 and 30% fat. AB - The effects of fat level (5, 12 and 30%), carrageenan and oat fibre on the hydration/binding properties, colour and flavour characteristics of frankfurters were investigated. Decreasing the fat content from 30% to 5% significantly increased cook loss and decreased water holding capacity and emulsion stability. Reduced-fat products were also darker and redder compared with the 30% fat controls. Addition of carrageenan or oat fibre reduced cook loss and increased both water holding capacity and emulsion stability. Sensory evaluation indicated that decreasing fat from 30% to 5% increased the intensity of smokiness, spiciness and saltiness and reduced the overall acceptability of the flavour. Carrageenan or oat fibre did not alter the colour of the frankfurters and neither ingredient had a significant effect on the flavour characteristics assessed. The results demonstrate that carrageenan or oat fibre can partially offset some of the changes which occur in low-fat frankfurters when added water replaces fat and protein level is constant. PMID- 22061467 TI - The effects of porcine somatotropin on muscle fibre morphology and meat quality of pigs of known stress susceptibility. AB - To study the effects of porcine somatotropin (pST) administration on muscle fibre characteristics and meat quality, 48 pigs of the Lacombe breed (equal numbers of barrows and gilts) of known halothane genotype (NN, Nn or nn) were randomly assigned to either a control (excipient buffer) or pST (3.0 mg d(-1)) treatment. At a pen average animal weight of 106 kg, pigs were slaughtered and muscle samples were collected post mortem for determination of fibre type, glucidic metabolites and meat quality. There was a 16% increase in muscle weight of the semimembranosus (SM) and psoas major (PM) in pST-treated animals (p <= 0.01). However, there was no significant change in fibre type associated with the pST treatment in either the SM or PM (p > 0.05). In the PM muscle there was a 65-70% increase in fast, oxidative, glycolytic (FOG) and fast, glycolytic (FG) fibre areas in pST-treated gilts (p <= 0.05). These cellular changes were manifest in meat colour that was lighter and spectrally shifted towards yellow (significantly higher L (*) and hue angle values), higher drip loss, lower moisture content and a tendency towards higher Kramer-Press shears (p = 0.06) in the PM of pST-treated gilts. Although these changes were in the same direction as pale, soft, exudative meat, the average values fell within the normal range. Based on the observed gender by pST treatment interactions, administration of pST (timing, dosage and protein requirements in the feed) may need to be tailored to suit different genders and breeds to achieve the maximal response. PMID- 22061468 TI - The distribution of dietary vitamin E in the muscles of the porcine carcass. AB - The objectives of this study were to determine the effect of dietary vitamin E supplementation on tissue alpha-tocopherol levels in muscles in the porcine carcass. Pigs (n = 9), were selected at random and divided into three groups (n = 3) and fed diets containing 0 (basal), 20, 160 mg dl-alpha-tocopheryl acetate/kg feed for a period of 130 days prior to slaughter. After slaughter carcasses were split centrally and chilled at 4 degrees C * 24 h. Muscles (n = 37) were identified and removed from the left side of each animal for each dietary group and stored at -20 degrees C until required. The mean alpha-tocopherol levels in pork muscle tissue were significantly (p < 0.05) higher in the high-supplemented group (160 mg alpha-tocopheryl acetate/kg of feed) compared with the low supplemented (20 mg/kg of feed) and basal groups (unsupplemented). In the supplemented samples, the muscles of the thoracic limb (4.8-9.9 mg alpha tocopherol/kg of tissue) and neck and thorax (3.7-9.2 mg/kg) contained the greatest levels of alpha-tocopherol compared the muscles of the pelvic limb (4 5.6 mg/kg) and back (2.5-3.5 mg/kg). PMID- 22061469 TI - Early post-mortem conditions and the calpain/calpastatin system in relation to tenderness of double-muscled beef. AB - Early post mortem temperature, pH, sarcomere length, colour, water holding capacity, calpain/calpastatin activities and myofibrillar protein concentrations (semi-quantative SDS-PAGE), measured at different times post mortem on 153 double muscled Belgian Blue White bulls, were related to shear force (SF) measurements. The M. longissimus thoracis tenderised up to 8 days post mortem. SF was slightly correlated with temperature at 3 h post mortem (r = 0.20, p = 0.015), but not with pH early post mortem. Higher ultimate pH values measured at 24 h post mortem were related to darker meat, lower cooking losses and shorter sarcomere lengths. Sarcomere length was significantly related to SF, even after 12 days of ageing, suggesting that proteolytic activity was not able to overcome shortening. Up to 12 days post mortem, calpastatin and m-calpain activities were significantly correlated with SF suggesting a considerable role of calpains in meat tenderization of double-muscled Belgian Blue White bulls, although at 24 h post mortem, MU-calpain could no longer be detected. Titin, nebulin, filamin and troponin-T were degraded during the ageing period. Troponin-T was degraded by 80% between day 1 and 8. At 8 days post mortem its concentration was significantly correlated with 30 kDa (r = 0.63, p = 0.00), shear force (r = 0.39, p = 0.00), calpastatin activity at 1 day post mortem (r = 0.29, p = 0.01) and with the m calpain/ calpastatin activity ratio at 1 day post mortem (r = -0.43, p = 0.00). PMID- 22061470 TI - Use of linear measurements of m. longissimus to predict the muscle content of beef carcasses. AB - Five linear measurements associated with the eye muscle (m. longissimus), together with hot carcass weight, 10th rib fat thickness, eye muscle area and an estimate of eye muscle volume (eye muscle area * a carcass length measurement) were made on 53 chilled beef carcasses (hot weight 143-384 kg). The right side of each carcass was anatomically dissected into muscle, bone, fat and connective tissue. Correlation and regression analyses were used to identify the most accurate predictors of weight and percentage of side muscle. In simple regression, hot carcass weight and the estimate of eye muscle volume were the most accurate predictors of side muscle weight; 10th rib fat thickness and MN, a depth measurement of muscle and fat over the loin, were the most accurate predictors of percentage side muscle. In multiple regression, the addition of either eye muscle volume or eye muscle area to hot carcass weight and 10th rib fat thickness gave the most accurate predictions of side muscle weight and percentage side muscle, but in the case of each dependent variable, the improvement in accuracy was slight compared with that of the two most accurate regressors, hot carcass weight and 10th rib fat thickness. Although eye muscle volume was a more accurate predictor of side muscle weight than eye muscle area in simple regression, their contributions in multiple regression with hot carcass weight and 10th rib fat thickness were similar. None of the five linear measurements associated with m. longissimus contributed significantly to improving the prediction of weight or percentage of side muscle. PMID- 22061471 TI - The effect of low-intensity ultrasound treatment on shear properties, color stability and shelf-life of vacuum-packaged beef semitendinosus and biceps femoris muscles. AB - A series of experiments were conducted to assess the impact of low-intensity ultrasound treatment on shear properties, color and shelflife of packaged beef muscles. For the first experiment, 15 beef semitendinosus muscles were sliced (6.4 * 2.5 * 70.2 cm) weighed, vacuum packaged, subjected to a 1.55 W/cm(2) intensity ultrasonic field for 8, 16 or 24 min then stored at 3 degrees C for 4 days; controls were not sonicated. Muscles were then removed from vacuum bags, weighed, cooked to 70 degrees C internal temperature in a convection oven and evaluated for cooking and shearing properties. For the second experiment, 14 beef semitendinosus muscles were sliced (2.5 * 5.1 * 10.2 cm), vacuum packaged and allocated to either a simultaneous ultrasound/water-bath-heating treatment or water-bath-heating treatment only. Muscles were removed from the water-bath when the water temperature reached 70 degrees C, removed from the vacuum bags, cooked further to an internal temperature of 70 degrees C in a convection oven and evaluated for instrumental shear. For the third experiment, 30 beef biceps femoris pieces (1.3 * 7.6 * 10.2 cm) were mixed together to more evenly distribute native microflora, vacuum packaged and allocated to either ultrasound (1.55 W/cm(2), 3 degrees C, 30 min) treatment or control (no ultrasound treatment). Vacuum-packaged muscles were stored in a retail display case (3 degrees C) and evaluated at 0, 5, 10, 20 and 30 days for microbial count and instrumental color (CIE L (*)a (*)b (*)). Ultrasound had no effect (p > 0.05) on storage purge loss, cooking loss, or textural properties (Experiments 1 and 2). Microbial levels were initially reduced (p < 0.05) by the ultrasound treatment (0 days), but differences in microbial numbers between ultrasound-treated samples and controls disappeared (p > 0.05) during storage (Experiment 3). PMID- 22061472 TI - Muscle protein changes post mortem in relation to pork quality traits. AB - The relationship between post-mortem traits of muscle proteins and water loss traits was investigated using 84 pork loins representing the four quality traits of PSE, RSE (reddishpink, soft, exudative), RFN (reddish-pink, firm, non exudative) and DFD. Protein solubility measurements (sarcoplasmic, myofibrillar and total) were lower and myosin denaturation (quantified by myofibrillar ATPase activity) was higher for PSE samples compared with samples from the other quality classes. RSE samples were similar to RFN samples in protein solubility and myosin denaturation, although RSE had lower values then DFD samples for protein solubility measurements. RFN samples had lower drip, thaw, cook and total water loss than RSE samples and all water loss traits were lowest for DFD samples and highest for PSE samples. Insoluble phosphorylase was the only characteristic that differentiated among PSE, RSE and RFN samples. SDS-PAGE and Western blots indicated that in PSE and RSE samples, the myofibrillar protein titin was less degraded and nebulin was more degraded compared with RFN and DFD samples. SDS PAGE of extracted and unextracted myofibrils showed that the reduced myofibrillar solubility of PSE samples was caused by decreased extractability of the myosin heavy chain in these samples. In conclusion, although RSE samples have unacceptably high water loss, muscle protein denaturation was minimal and did not explain the low water-holding capacity. PMID- 22061473 TI - Discrimination between fresh and frozen-then-thawed beef m. longissimus dorsi by combined visible-near infrared reflectance spectroscopy: A feasibility study. AB - Investigations into the classification of meat samples as either fresh or frozen then-thawed have been performed using near infrared spectroscopy and two chemometric techniques: factorial discriminant analysis and SIMCA. Work was performed on meat pieces using a fibre optic probe for spectral acquisition. A sample of meat (m. longissimus dorsi) from each of 32 animals of a single species (female Hereford-cross) was collected from a commercial abattoir. Using a standard freeze-thaw regime, results reported show a significant rate of discrimination between fresh and frozen-then-thawed beef for the factorial discriminant procedure; SIMCA was less successful. PMID- 22061474 TI - Effect of different cooking methods on some lipid and protein components of hamburgers. AB - The effects of different cooking methods on the lipid and protein fractions of hamburger were evaluated. The lipid component was subjected to the following analyses: peroxide value; p-anisidine; total and free fatty acids; cholesterol and its oxidation products (quantified as 7-ketocholesterol). Lysinoalanine (LAL), free amino acids and D-amino acids (D-AA) were also determined in the protein fraction. All results were compared with a raw control. No significant differences were found among the cooking treatments with respect to D-AA and LAL. The degree of proteolysis, lipolysis and lipid oxidation varied depending on the treatment conditions. Regarding cholesterol oxidation, the combination of roasting and microwave heating caused more oxidation than the other treatments. The raw meat, however, showed an advanced degree of oxidation (25.2 ppm of total 7-ketocholesterol/120 g ground meat). PMID- 22061475 TI - Effect of water temperature, pressure and chemical solution on removal of fecal material and bacteria from lamb adipose tissue by spray-washing. AB - The objectives of this study were to determine the efficacy of various water temperatures, pressures and chemical solutions of spray-washing on the removal of fecal and bacterial contamination from lamb carcass samples taken from the breast area (< 15 min post mortem) and inoculated (6.50 cm(2) area) with an ovine fecal paste containing Escherichia coli (ATCC 11370). Inoculated samples were held for 15 min and then knife-trimmed and/or spraywashed with varying water temperatures (16, 35 or 74 degrees C), pressures (2.76, 13.79, 20.68 or 27.58 bar) and chemical solutions (12% trisodium phosphate, 2% acetic acid, 5% hydrogen peroxide or 0.003% available chlorine) for 18 s. After the respective treatments, samples were evaluated visually for presence of fecal material and microbiologically for aerobic plate counts (APC). Knife-trimming reduced (p < 0.05) APC of inoculated samples, while subsequent spray-washing of knife-trimmed samples reduced APC (p < 0.05), even compared to uninoculated control samples. Spray-washing with any temperature and pressure combination reduced (p < 0.05) visible fecal contamination on the samples. Bacterial reductions ranged from 1.48 to 3.83 log colony forming units (CFU/cm(2)) at the inoculation site. Use of 74 degrees C water was more effective (p < 0.05) in decreasing APC than either 16 or 35 degrees C water, while water pressure effects were similar. Use of 2% acetic acid reduced the APC more than the use of any other chemical solution tested. APC for the areas surrounding the inoculation site were similar to APC at the inoculation site; thus indicating that either there was no major spread of bacterial contamination to areas above or below the inoculation site or that contamination was diluted to levels lower than initial contamination. Overall, acetic acid and water temperature were the most important factors in reducing APC and fecal contamination on lamb adipose tissue. PMID- 22061476 TI - Technology for meat-grinding systems to improve removal of hard particles from ground meat. AB - With increased consumption of ground meat, especially ground beef, quality issues for these products have become more important to industry and consumers alike. Ground meats are usually obtained from relatively low-value cuts and trimmings, and may on occasion contain undesirable hard particles. Hard particles in coarse ground meat products may include bone chips or fragments, cartilage and dense connective tissue; all of which are considered undesirable defects and which can be reduced by utilizing hard-particle removal systems during grinding operations. This review discusses the principles of hard-particle separation from ground meat, the factors which influence performance of particle separation and some commercially available particle removal systems. Product and processing parameters such as initial bone and connective tissue content, fat content, temperature, pre-grinding size and grinder knife design are considered important for removing hard particles effectively. Pressure gradient on the grinder knife/plate interface was found to play a significant role in particle separation from soft (fat and lean) tissue. Various commercial systems, which are classified as central removal and periphery removal systems, are also discussed. Finally, the authors suggest some processing considerations for meat grinding to help achieve the best quality ground meat for consumers' satisfaction. PMID- 22061477 TI - Analysis of restriction fragment length polymorphism in the bovine growth hormone gene related to growth performance and carcass quality of Korean Native Cattle. AB - This research was conducted to find restriction fragment length polymorphism (RFLP) markers related to growth performance and meat quality of Korean Native Cattle. DNA was extracted from the blood of Korean Native Cattle steers and Southern blot analysis of genomic DNA digested with restriction enzymes was performed using a bovine growth hormone (GH) cDNA probe. The restriction enzyme that detected RFLPs most frequently was TaqI. Digested fragments with TaqI revealed 6.15, 5.2, 4.5, 4.3, 2.6, 2.4, 1.6, 0.5, 0.3 and 0.2 kb bands. The most frequent band was 1.6 kb, which was exhibited in 11 out of 15 animals. In GH-TaqI RFLP, the 4.3 kb band was correlated with average daily gain (p = 0.021) and carcass weight (p = 0.035). No markers related to meat quality were found. PMID- 22061478 TI - Inhibition of metmyoglobin formation in fresh beef by pressure treatment. AB - Application of pressures of 80-100 MPa for 20 min improved the colour stability, as measured by rate of metmyoglobin formation, of longissimus dorsi and psoas major beef muscles exposed to air 2 days post-slaughter. However, pressure treatment of these muscles at 7-20 days post-slaughter did not improve their colour stability. It is suggested that pressure inhibits, at least partially, the mechanism(s) responsible for the low colour stability of very fresh beef. PMID- 22061479 TI - Bladder exstrophy and extreme genital anomaly in a patient with pure terminal 1q deletion: expansion of phenotypic spectrum. AB - We describe a 5 2/12 years old male patient with a de novo deletion 1q43q44 of approximately 10.4 Mb in size. The boy presented with the classic features of chromosome 1q43q44 deletion syndrome including growth and psychomotor retardation, microcephaly, distinct facial features and various midline defects as agenesis of corpus callosum, cardiac and urogenital anomalies. Fronto-parietal simplified gyral pattern was an additional neuroimaging finding. The urogenital anomalies in our patient were remarkable in form of bladder exstrophy and severe hypogenitalism with a marked hypoplastic scrotum, small sized retractile testis and absent phallus. To the best of our knowledge, bladder exstrophy and absence phallus have not been previously reported in terminal deletion 1q43q44 syndrome. This report provides further evidence of phenotype-genotype correlation and expands the phenotypic spectrum of midline defects described with this syndrome. PMID- 22061480 TI - Functional genomics identifies neural stem cell sub-type expression profiles and genes regulating neuroblast homeostasis. AB - The Drosophila larval central brain contains about 10,000 differentiated neurons and 200 scattered neural progenitors (neuroblasts), which can be further subdivided into ~95 type I neuroblasts and eight type II neuroblasts per brain lobe. Only type II neuroblasts generate self-renewing intermediate neural progenitors (INPs), and consequently each contributes more neurons to the brain, including much of the central complex. We characterized six different mutant genotypes that lead to expansion of neuroblast numbers; some preferentially expand type II or type I neuroblasts. Transcriptional profiling of larval brains from these mutant genotypes versus wild-type allowed us to identify small clusters of transcripts enriched in type II or type I neuroblasts, and we validated these clusters by gene expression analysis. Unexpectedly, only a few genes were found to be differentially expressed between type I/II neuroblasts, suggesting that these genes play a large role in establishing the different cell types. We also identified a large group of genes predicted to be expressed in all neuroblasts but not in neurons. We performed a neuroblast-specific, RNAi-based functional screen and identified 84 genes that are required to maintain proper neuroblast numbers; all have conserved mammalian orthologs. These genes are excellent candidates for regulating neural progenitor self-renewal in Drosophila and mammals. PMID- 22061481 TI - Time-lapse imaging reveals stereotypical patterns of Drosophila midline glial migration. AB - The Drosophila CNS midline glia (MG) are multifunctional cells that ensheath and provide trophic support to commissural axons, and direct embryonic development by employing a variety of signaling molecules. These glia consist of two functionally distinct populations: the anterior MG (AMG) and posterior MG (PMG). Only the AMG ensheath axon commissures, whereas the function of the non ensheathing PMG is unknown. The Drosophila MG have proven to be an excellent system for studying glial proliferation, cell fate, apoptosis, and axon-glial interactions. However, insight into how AMG migrate and acquire their specific positions within the axon-glial scaffold has been lacking. In this paper, we use time-lapse imaging, single-cell analysis, and embryo staining to comprehensively describe the proliferation, migration, and apoptosis of the Drosophila MG. We identified 3 groups of MG that differed in the trajectories of their initial inward migration: AMG that migrate inward and to the anterior before undergoing apoptosis, AMG that migrate inward and to the posterior to ensheath commissural axons, and PMG that migrate inward and to the anterior to contact the commissural axons before undergoing apoptosis. In a second phase of their migration, the surviving AMG stereotypically migrated posteriorly to specific positions surrounding the commissures, and their final position was correlated with their location prior to migration. Most noteworthy are AMG that migrated between the commissures from a ventral to a dorsal position. Single-cell analysis indicated that individual AMG possessed wide-ranging and elaborate membrane extensions that partially ensheathed both commissures. These results provide a strong foundation for future genetic experiments to identify mutants affecting MG development, particularly in guidance cues that may direct migration. Drosophila MG are homologous in structure and function to the glial-like cells that populate the vertebrate CNS floorplate, and study of Drosophila MG will provide useful insights into floorplate development and function. PMID- 22061484 TI - Differing views of children and parents: some cautionary tales! PMID- 22061485 TI - Atopic manifestations during childhood and fetal exposure to arachidonic acid. PMID- 22061487 TI - Decorated graphene sheets for label-free DNA impedance biosensing. AB - An efficient DNA impedance biosensing platform is constructed, in which positively charged N,N-bis-(1-aminopropyl-3-propylimidazol salt)-3,4,9,10 perylene tetracarboxylic acid diimide (PDI) is anchored to graphene sheets. The pi-pi stacking and electronic interactions are elucidated by the distinct absorption features in UV-vis spectra and by quenching perylene fluorescence in contact with graphene. The rational design and tailoring of graphene surface invest it with desired properties (dispersive, structural, photoelectrical and conductive, etc.) and boost its application. Electrostatic interaction between PDI's positively charged imidazole rings and negatively charged phosphate backbones of single-stranded DNA (ssDNA) facilitates ssDNA immobilization. This manner is different from these mainly based on the attraction between the rings in DNA bases and the hexagonal cells of graphene, which is disturbed after hybridization and causes the leaving of formed double-stranded DNA from graphene surface. The electrostatic ssDNA grafting occupies phosphate backbones and particularly leaves the bases available for efficient hybridization. DNA immobilization and hybridization lead to PDI/graphene interfacial property changes, which are monitored by electrochemical impedance spectroscopy and adopted as the analytical signal. The conserved sequence of the pol gene of human immunodeficiency virus 1 is satisfactorily detected via this PDI/graphene platform and shows high reproducibility, selectivity. PMID- 22061488 TI - Microfluidic 3D bone tissue model for high-throughput evaluation of wound-healing and infection-preventing biomaterials. AB - We report the use of a microfluidic 3D bone tissue model, as a high-throughput means of evaluating the efficacy of biomaterials aimed at accelerating orthopaedic implant-related wound-healing while preventing bacterial infection. As an example of such biomaterials, inkjet-printed micropatterns were prepared to contain antibiotic and biphasic calcium phosphate (BCP) nanoparticles dispersed in a poly(D,L-lactic-co-glycolic) acid matrix. The micropatterns were integrated with a microfluidic device consisting of eight culture chambers. The micropatterns immediately and completely killed Staphylococcus epidermidis upon inoculation, and enhanced the calcified extracellular matrix production of osteoblasts. Without antibiotic elution, bacteria rapidly proliferated to result in an acidic microenvironment which was detrimental to osteoblasts. These results were used to demonstrate the tissue model's potential in: (i) significantly reducing the number of biomaterial samples and culture experiments required to assess in vitro efficacy for wound-healing and infection prevention and (ii) in situ monitoring of dynamic interactions of biomaterials with bacteria as wells as with tissue cells simultaneously. PMID- 22061489 TI - Sustained local delivery of siRNA from an injectable scaffold. AB - Controlled gene silencing technologies have significant, unrealized potential for use in tissue regeneration applications. The design described herein provides a means to package and protect siRNA within pH-responsive, endosomolytic micellar nanoparticles (si-NPs) that can be incorporated into nontoxic, biodegradable, and injectable polyurethane (PUR) tissue scaffolds. The si-NPs were homogeneously incorporated throughout the porous PUR scaffolds, and they were shown to be released via a diffusion-based mechanism for over three weeks. The siRNA-loaded micelles were larger but retained nanoparticulate morphology of approximately 100 nm diameter following incorporation into and release from the scaffolds. PUR scaffold releasate collected in vitro in PBS at 37 degrees C for 1-4 days was able to achieve dose-dependent siRNA-mediated silencing with approximately 50% silencing achieved of the model gene GAPDH in NIH3T3 mouse fibroblasts. This promising platform technology provides both a research tool capable of probing the effects of local gene silencing and a potentially high-impact therapeutic approach for sustained, local silencing of deleterious genes within tissue defects. PMID- 22061490 TI - PEGylated dendrimer-entrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography. AB - We report the synthesis and characterization of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with enhanced biocompatibility for computed tomography (CT) imaging applications. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH(2)) modified by PEG monomethyl ether (G5.NH(2)-mPEG(20)) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines to generate PEGylated Au DENPs. The partial PEGylation modification of dendrimer terminal amines allows high loading of Au within the dendrimer interior, and consequently by simply varying the Au salt/dendrimer molar ratio, the size of the PEGylated Au DENPs can be controlled at a range of 2-4 nm with a narrow size distribution. The formed PEGylated Au DENPs are water-dispersible, stable in a pH range of 5-8 and a temperature range of 0-50 degrees C, and non cytotoxic at a concentration as high as 100 MUm. X-ray absorption coefficient measurements show that the attenuation intensity of the PEGylated Au DENPs is much higher than that of Omnipaque with iodine concentration similar to Au. With the sufficiently long half-decay time demonstrated by pharmacokinetics studies, the PEGylated Au DENPs enabled not only X-ray CT blood pool imaging of mice and rats after intravenous injection of the particles, but also effective CT imaging of a xenograft tumor model in nude mice. These findings suggest that the designed PEGylated Au DENPs can be used as a promising contrast agent with enhanced biocompatibility for CT imaging of various biological systems, especially in cancer diagnosis. PMID- 22061491 TI - Multifunctional nanocarrier mediated co-delivery of doxorubicin and siRNA for synergistic enhancement of glioma apoptosis in rat. AB - As the most fatal malignancy in brain, glioma cannot be effectively treated with the conventional chemotherapy and thus techniques which may improve the chemotherapeutic effect are of great importance in clinical glioma treatment. Based on the folate-targeted multifunctional nanocarrier developed in our lab, effective co-delivery of DOX and siRNA into rat C6 glioma cells over-expressing folate receptors was achieved. Although cell apoptosis was initiated even at low DOX doses such as 0.5 MUg/mL in the DOX-alone treatment mediated by the folate targeted nanocarrier, anti-apoptotic response in C6 cells was activated as well, as revealed by molecular biological investigations. Delivery of BCL-2 siRNA using the folate-targeted nanocarrier can effectively suppress the anti-apoptotic response and sensitized C6 cells to DOX treatment both in vitro and in vivo. In particular, animal studies using the in situ rat C6 glioma model showed that the folate-targeted co-delivery of BCL-2 siRNA and DOX caused not only an obvious down-regulation of the anti-apoptotic BCL-2 gene but also a remarkable up regulation of the pro-apoptotic Bax gene, resulting in the significantly elevated level of caspase-3 activation and remarkable cell apoptosis in tumor tissues. Our results strongly demonstrated the synergistic effect of siRNA and DOX in inducing glioma C6 cell apoptosis, upon which an excellent therapeutic effect was achieved using the folate-targeted co-delivery strategy as indicated by the effective tumor growth inhibition and prolonged rat survival time in the animal test. PMID- 22061492 TI - Highly dynamic biodegradable micelles capable of lysing Gram-positive and Gram negative bacterial membrane. AB - The development of biodegradable antimicrobial polymers adds to the toolbox of attractive antimicrobial agents against antibiotic-resistant microbes. To this end, the potential of polycarbonate polymers as such materials were explored. A series of random polycarbonate polymers consisting of monomers MTC-OEt and MTC CH(2)CH(3)Cl were designed and synthesized using metal-free organocatalytic ring opening polymerization. Random polycarbonate polymers self-assembled in solution but appeared highly dynamic; such behaviors are desirable as ready disassembly of polymers at the microbial membrane facilitates membrane disruption. Their activities against clinically relevant Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (E.coli and Pseudomonas aeruginosa) revealed that the hydrophobic-hydrophilic composition balance in polymers are important to render antimicrobial potency. Scanning electron microscopy (SEM) studies indicated microbial cell surface damage after treatment with polymers, and confocal microscopy studies also showed entry of FITC-dextran dye in Escherichia coli as a result of membrane disruption. On the other hand, the polymers exhibited minimal toxicity against red blood cells in hemolysis tests. Therefore, these random polycarbonate polymers are promising antimicrobial agents against both Gram positive and Gram-negative bacteria for various biomedical applications. PMID- 22061493 TI - Multifunctional nanoprobes for upconversion fluorescence, MR and CT trimodal imaging. AB - Early diagnosis probes that combine fluorescence, X-ray computed tomography (CT) and magnetic resonance (MR) imagings are anticipated to give three dimensional (3D) details of tissues and cells of high resolution and sensitivity. However, how to combine these three modalities together within a sub-50 nm sized structure is technically challenging. Here we report a trimodal imaging probe of PEGylated NaY/GdF(4): Yb, Er, Tm @SiO(2)-Au@PEG(5000) nanopaticles of uniform size of less than 50 nm. The as-designed nanoprobes showed (1) strong emissions ranging from the visible (Vis) to near infrared (NIR) for fluorescent imaging, (2) T(1) weighted MRI by shorting T(1) relaxation time and (3) enhanced HU value as a CT contrast agent. The structure was optimized based on a comprehensive investigation on the influence of the distance between the NaY/GdF(4): Yb, Er, Tm core and Au nanoparticles (NPs) at the surface. The potential of trimodal imaging for cancerous cells and lesions was further demonstrated both in vitro and in vivo. PMID- 22061494 TI - Simultaneous electrochemical detection of multiple analytes based on dual signal amplification of single-walled carbon nanotubes and multi-labeled graphene sheets. AB - In this work, a sandwich-type electrochemical aptasensor for simultaneous sensitive detection of platelet-derived growth factor (PDGF) and thrombin is fabricated. Reduced graphene oxide sheets (rGS) are used as matrices to immobilize the redox probes, which are subsequently coated with platinum nanoparticles (PtNPs) to form the PtNPs-redox probes-rGS nanocomposites. With the employment of the as prepared nanocomposites, a signal amplification strategy was described based on bienzyme (glucose oxidase and horseradish peroxidase) modified PtNPs-redox probes-rGS nanocomposites as the tracer labels for secondary aptamers (Apt II) through sandwiched assay. Gold nanoparticles functionalized single walled carbon nanotubes (AuNPs@SWCNTs) as the biosensor platform enhance the surface area to capture a large amount of primary aptamers (Apt I), thus amplifying the detection response. The experiment results show that the multi labeled PtNPs-redox probes-rGS nanocomposites display satisfying electrochemical redox activity and highly electrocatalytic activity of PtNPs and bienzyme, which exhibit high sensitivity for detection of proteins. The linear range of PDGF is 0.01-35 nM with a detection limit of 8 pM, while the linear ranges from 0.02 to 45 nM and a detection limit of 11 pM for thrombin are obtained. PMID- 22061496 TI - Detection of mechanically recovered meat and head meat from cattle in ground beef mixtures by multivariate analysis of isoelectric focusing protein profiles. AB - The present work investigates the possibility of constructing a multivariate calibration model for predicting the composition of ground beef with respect to different meat quality types, based on intensity profiles from isoelectric focusing of water-soluble proteins. Beef mixtures containing various amounts of mechanically recovered meat, head meat and production meat from beef, were analysed by isoelectric focusing in immobilised pH-gradients. The gels were photographed and the images transferred to a digital format. By simple image processing procedures, background colour was virtually eliminated and signal strength was improved to a considerable degree. Multivariate analysis of protein profiles from the gels gave models explaining 75 to 90% of variance in sample composition. Manually deboned meat was explained to the highest degree, and with a precision of 7%. Two different qualities of mechanically recovered meat could be detected even when treated as one category. The present approach needs further refinement, but seems applicable for detecting intentional substitution of high quality meat products with low-price raw materials. One advantage of the approach is that evaluation of samples is not dependent on specific knowledge on the individual components to be analysed, so that such analytical methods are relatively easy to implement in any standard laboratory. PMID- 22061497 TI - Assessment of meat fat content using dual energy X-ray absorption. AB - Fat content is an essential component of meat quality. Fat content and fatty tissue content were determined by dual energy X-ray absorption on 3 types of meat: pork meat (mixture of longissimus dorsi and fat) and beef meat (longissimus dorsi and pectoralis profondus). The measurements were carried out with a medical densitometer, the SOPHOS L-XRA usually used for osteodensitometry. The results from the dual energy X-ray absorption and the chemical analysis were compared and the correlations were good to very good (R(2) values from 0.7 to 0.97). The residual standard deviations were in the range 2.75-4.89%. The routine use of dual energy X-ray absorption would though suppose a previous calibration. PMID- 22061498 TI - Sensory quality and cooking loss of ham muscle (M. biceps femoris) from pigs reared indoors and outdoors. AB - The aim of this study was to evaluate the sensory characteristics and cooking loss of ham from pigs of different genotype and sex and on different rearing systems. Half of each litter was reared indoors in a large pen (120 mm(2)), and the other half outdoors. Ham muscles (M. biceps femoris) from 48 Hampshire crosses (carriers or non-carriers of the RN(-) allele) were subjected to sensory evaluation by means of descriptive analysis by a selected and trained nine-member panel. Ham from RN(-) carriers scored higher than that from non-carriers with regard to smell intensity and meat taste, also it was more tender and tended to have a more acidulous taste. Ham from pigs reared indoors had a juicier and more acidulous taste than that from pigs reared outdoors. Ham from castrates was more tender and more juicy than ham from gilts. PMID- 22061499 TI - Effect of calcium chloride marination on bovine Cutaneus trunci muscle. AB - The aim of this investigation was to determine the possibility of using calcium chloride solution in tough muscles (Cutaneus trunci) to reduce the aging period required to increase tenderness, without introducing undesirable flavors. Muscles were marinated in 0.25 M CaCl(2) solution for 2 h and after that aged for 0, 1, 2, 3, 4, 5 and 7 days. Tenderness was evaluated by the myofibrillar fragmentation index (MFI), Warner Bratzler shear force (WBS) and sensory panel evaluation. MFI values showed significant differences between treated and control samples aged for 1, 2 and 3 days (P<0.05). MFI values of treated samples aged 3 days were similar to those obtained for the control samples but aged seven days. WBS values were not significantly different between samples. Consumer panelists preferred treated samples aged 3 days to the control ones aged 7 days. It was concluded that calcium chloride treatment can be used in Cutaneus trunci muscle to reduce the aging time required to increase tenderness. PMID- 22061500 TI - Effect of rate of pH decline on muscle enzyme activities in two pig lines. AB - Muscle enzyme activities were measured in m. transversus abdominis (TA) samples of two pig lines, differing in stress sensitivity and in breeding objectives. Animals of line one were stress sensitive and selected for a high carcass lean content (LEAN), those of line two were homozygous stress resistant and selected for maximum live weight gain (GROWTH). Muscle samples of 16 pigs per line were excised at 1 h and sampled at 3 h post mortem. Boars, gilts and barrows were almost equally represented. Pigs of line GROWTH had a higher fat and lean tissue gain (P<0.01) and a lower carcass lean content (P<0.001) than those of line LEAN. Lower activities of MU-calpain, m-calpain, pyroglutamyl aminopeptidase I, acid lipase and neutral phospholipase were measured in TA muscle samples of line LEAN compared with line GROWTH (P<0.05). Activities of dipeptidyl peptidase IV and acid phospholipase tended to be somewhat lower for line LEAN, whereas activities of calpastatin, cathepsin (B+L) and cathepsin D were not different. Sex-class effects were analogous to line effects. Significant correlation coefficients between activities of several enzymes and pH values 1 h post mortem, both within and across lines, suggest that lower enzyme activities are a consequence of a more pronounced denaturation due to a faster post mortem pH decline. PMID- 22061501 TI - Effects of stress and high voltage electrical stimulation on tenderness of lamb m. longissimus. AB - This study was conducted to investigate the reported effect of pre-slaughter stress on meat tenderness independent from its effect on ultimate pH, and its interaction with electrical stimulation. From a group of 80 Coopworth lamb, 40 were stressed by subjecting the animals to a swim wash 3 h before slaughter and the use of dogs to assemble the animals to the access ramp of the abbatoir. Half of the carcasses of each group was electrically stimulated within 30 min post mortem. Temperature and pH decline of the longissimus was monitored and shear force of the cooked muscle was determined at 2 days post mortem and after 6 weeks vacuum storage at 1 degrees C. To investigate an effect of stress independent of ultimate pH, 10 muscles with an ultimate pH below 5.8 were selected from each group for detailed analysis. This analysis consisted of determination of calpastatin activity and sarcomere length, and immunoblotting of MU-calpain and calpain substrates. The stress treatment led to an increase in the number of muscles with an ultimate pH above 5.8 (32.5 vs 15%), and muscles with an ultimate pH above 5.8 were significantly tougher than muscles with an ultimate pH below 5.8 at 2 days post mortem. Electrical stimulation improved tenderness at two days post mortem. This effect could be attributed to an effect on muscle contraction, but not on post mortem proteolysis of calpain substrates. A large variation in tenderness at 2 days post mortem was observed and this was not reduced by electrical stimulation. Six weeks of vacuum storage resulted in a 6 kgF drop in mean shear force and a uniformly tender product. Despite the fact that the stress treatment was similar to those in earlier studies, we failed to observe an effect of stress independent of ultimate pH on tenderness. The reason for this is unclear, but differences in the response to stress between breeds may be responsible. The results of the present study underscore the importance of minimizing pre-slaughter stress and adequate post mortem storage for meat quality. PMID- 22061502 TI - Shelf life of beef from local Spanish cattle breeds stored under modified atmosphere. AB - Beef steaks from six Spanish cattle breeds (Asturiana de los Valles, Morucha, Parda Alpina, Pirenaica, Rubia Gallega and Retinta) were packaged under modified atmosphere (60% O(2), 30% CO(2) and 10% N(2)). Water loss, pH, thiobarbituric acid values (TBA), aerobic plate counts, lactic acid bacteria and Enterobacteriaceae counts, CIE L*a*b* colour values and the sensory properties of odour and colour were recorded before packaging (day 0) and after 5, 10 and 15 days of storage. A significant interaction (P<0.05) between breed and storage time was found for all variables, except water loss. Values of pH were between 5.3 and 5.6; maximum water loss (2.64%) was reached after 10 days of storage; aerobic plate counts, lactic acid bacteria and Enterobacteriacea counts were lower than 10(7) CFU/g, and L* increased with storage time while a* decreased (P<0.05). The maximum shelf life of beef assessed by sensory evaluation (regarding colour and odour degradation) was between days 5 and 10 in meat from Retinta breed and between days 10 and 15 in meat from the other breeds, shelf life was probably limited by lipid oxidation. PMID- 22061503 TI - Role of cysteine endopeptidases (EC 3.4.22) in rabbit meat tenderisation and some related changes. AB - The role of endogenous cysteine endopeptidases (EC 3.4.22; calpains and cathepsins B, L and H) in rabbit (Oryctolagus cuniculus L.) meat tenderisation and some related changes (formation of the 30 kDa fragment and myofibrillar structure weakening), during ageing (9 days at +4 degrees C), was studied for different types of muscle (I, IIB and IID). The results strongly suggest that cysteine peptidases, possibly calpains, play a major role in rabbit meat tenderisation, myofibrillar structure weakening and formation of the 30 kDa fragment in type II muscles. Cathepsins B, L and H appear to have no role in these changes during rabbit meat ageing. The results also indicate that myofibrillar fragmentation and the contents of the 30 kDa fragment are good ageing indices for rabbit meat. Finally, it is suggested that the weakening of the myofibrillar structure, unlike the formation of the 30 kDa fragment, might be directly involved in rabbit meat tenderisation. PMID- 22061504 TI - Survival and growth of Escherichia coli O157:H7, Yersinia enterocolitica and Salmonella enteritidis on decontaminated and untreated meat. AB - Decontamination of meat or carcasses may have an effect in reducing the number of pathogens. Recontamination with other pathogens during cutting or packaging may, however, result in higher growth on decontaminated than on untreated meat due to the lack of competing non-pathogenic microorganisms. In this study we compared the growth of pathogens during storage at 10 degrees C (worst case condition) on untreated meat and meat that had been decontaminated by steam vacuuming combined with spraying with 0.2 M lactic acid. Salmonella enteritidis inoculated on chicken multiplied quickly and reached log 7 cfu per cm(2) after 4 days of aerobic storage at 10 degrees C, but growth was not significantly higher on decontaminated than on untreated chicken. The number of Yersinia enterocolitica inoculated on decontaminated pork skin reached log 9 cfu per cm(2) after 5 days of aerobic storage at 10 degrees C. Overall, growth on vacuum-packed decontaminated and untreated pork under the same conditions was not significantly different, although there tended to be less growth on the untreated samples. The number of Escherichia coli O157:H7 on decontaminated beef increased by nearly 3 log cycles after 5 days of aerobic storage at 10 degrees C compared to only a 1 log cycle increase on untreated beef. For the vacuum-packed beef, growth of E. coli O157:H7 on the fresh meat was very slow, while there was about a 3 log increase on the decontaminated beef. A higher average growth on the decontaminated beef was also found in an experiment with a very low inoculum (27 cfu per cm(2)). During storage of vacuum-packed samples there was multiplication of E. coli O157:H7 on the decontaminated beef, but virtually none on the untreated beef. This study shows that multiplication of S. enteritidis on chicken and Y. enterocolitica on pork skin was not significantly higher on decontaminated compared to untreated meat. The increased multiplication of E. coli O157:H7 on decontaminated beef, especially when vacuum-packed, gives cause for concern. Preventive measures might be a strict HACCP approach to the handling of the decontaminated meat before packaging or use of a protective culture of lactic acid bacteria. PMID- 22061505 TI - Two-dimensional visible/near-infrared correlation spectroscopy study of thawing behavior of frozen chicken meats without exposure to air. AB - The thawing behavior of frozen chicken meats without exposure to air was investigated by generalized 2D Vis/NIR correlation spectroscopy. The synchronous 2D visible correlation analysis revealed that intensities of the 435 and 555 nm bands increase, because of the relaxation of DeoxyMb and OxyMb components, whereas those of the 475 and 620 nm bands decrease as MetMb and SulfMb decompose into small molecules due to specific enzymes. The corresponding asynchronous spectra indicated that the decomposition of MetMb and SulfMb species precedes the recovery of DeoxyMb and OxyMb, and that the DeoxyMb species recovers faster than the OxyMb. Further, the asynchronous 2D NIR spectra suggested that the melting of ice crystals and the relaxation and proteolysis of proteins occurs earlier, indicating a coordination process for hydrophilic O-H and N-H groups. Moreover, strong correlation peaks correlating the bands in the visible and NIR spectral regions were observed and discussed. PMID- 22061506 TI - Differences in molecular structure among the porcine myosin heavy chain-2a, -2x, and -2b isoforms. AB - Full coding regions for fast type myosin heavy chain (MyHC) isoforms were sequenced from a porcine skeletal muscle to analyze sequence diversity relating to the contractile properties of muscle fibers. An approximately 6-kb fragment for each MyHC was amplified through RT-PCR using isoform type-specific primers, which were designed in the 5' and 3' non-coding regions of the porcine MyHCs. The lengths of deduced amino acid sequences were 1939, 1939, and 1937 for the porcine MyHC-2a,-2x, and-2b, respectively. The entire amino acid sequences were highly conserved among the three MyHCs, except for the 50/20 k junction region (loop 2) which would weakly bind actin molecules. The porcine MyHC-2b possessed different amino acids from MyHC-2a and-2x, in loop1 and ELC binding region. The sequence data suggested the diversity of contractile properties among the porcine MyHC isoforms. PMID- 22061507 TI - Peptide inhibitors for angiotensin I-converting enzyme from enzymatic hydrolysates of porcine skeletal muscle proteins. AB - Inhibitors of angiotensin I-converting enzyme (ACE) have been shown to have antihypertensive effects and have been utilized for pharmaceuticals and physiologically functional foods. In the present study, efforts were directed to find ACE inhibitory activities derived from muscle proteins. Porcine skeletal muscle proteins were hydrolyzed by eight proteases, and the inhibitory activities of the hydrolysates toward ACE were measured. Among the digests of the water insoluble protein fraction prepared from muscle, thermolysin digest demonstrated the highest activity. Also, among hydrolysates of porcine myosin produced by the same enzymes, thermolysin digest showed the most potent inhibitory activity. Two ACE inhibitory peptides were purified from thermolysin digest of myosin. The sequences of these inhibitory peptides, named myopentapeptides A and B, were Met Asn-Pro-Pro-Lys and Ile-Thr-Thr-Asn-Pro. These sequences were found in the primary structure of the myosin heavy chain. The concentrations of the peptides showing 50% inhibition values (IC(50)) of ACE were 945.5 and 549.0 MUM, respectively. Also, six tripeptides, Met-Asn-Pro, Asn-Pro-Pro, Pro-Pro-Lys, Ile Thr-Thr, Thr-Thr-Asn, and Thr-Asn-Pro, which have parts of the sequences of the myopentapeptides, demonstrated activity. Their IC(50) values were 66.6, 290.5, >1000, 678.2, 672.7, and 207.4 MUM, respectively. PMID- 22061508 TI - Effect of extraction buffer on estimating calpain and calpastatin activity in postmortem ovine muscle. AB - The effect of extraction buffer on extractable calpain and calpastatin activity in postmortem muscles was examined. Muscles were removed from ovine carcasses 24 h after slaughter and extracted with three volumes of two extraction buffers containing 20 (pH 7.5) and 100 (pH 8.3) mM Tris. There was a significant difference in pH of the muscle homogenates, having a pH of 5.84 and 7.58 for 20 and 100 mM Tris base, respectively. Calpastatin, MU-calpain and m-calpain all had significantly reduced activity in extracts made with 20 mM Tris (pH 7.5) buffer compared to 100 mM Tris (pH 8.3) buffer, showing a loss of, respectively, 30, 57 and 37%. These results indicate the impact of choice of buffer on the extractable calpains and calpastatin activity from postmortem muscle. To avoid loss of calpains due to isoelectric precipitation, the pH of the muscle homogenate (after homogenization and prior to the first centrifugation) must be above 6.2. PMID- 22061509 TI - Antioxidative effect of dietary tea catechins on lipid oxidation of long-term frozen stored chicken meat. AB - The antioxidative effect of dietary tea catechins (TC) supplementation at levels of 50, 100, 200 and 300 mg kg(-1) feed on susceptibility of chicken breast and thigh meat to lipid oxidation during frozen (-20 degrees C) storage for 9 months was investigated. Day-old chickens (Cobb 500, n=200) were randomly divided into six groups. Chickens were fed a basal diet containing 20 mg alpha-tocopheryl acetate kg(-1) feed as control, or a vitamin E supplemented diet (basal diet plus 200 mg alpha-tocopheryl acetate kg(-1) feed), or TC supplemented diets (basal diet plus 50, 100, 200 or 300 mg TC kg(-1) feed) for 6 weeks prior to slaughter. Lipid oxidation (TBARS) was assessed after 0 and 10 days of refrigerated display (4 degrees C) following 1, 3, 6, and 9 months of frozen (-20 degrees C) storage. TC supplementation at all concentrations showed antioxidative effects for both breast and thigh chicken meat during the 9 months of frozen storage compared to the control sample. TC supplementation at levels of 200 and 300 mg kg(-1) feed were more effective (P<0.05) in delaying lipid oxidation in all meat samples compared to the control. TC supplementation at a level of 200 mg kg(-1) feed showed antioxidant activity equivalent to alpha-tocopheryl acetate fed at the same level up to 3 months of frozen storage. For long-term frozen storage up to 9 months, however, TC supplementation at 300 mg kg(-1) feed was required as a replacement for alpha-tocopheryl acetate at a level of 200 mg kg(-1) feed. The results obtained showed a long-term antioxidative effect exhibited by dietary tea catechins on chicken meat during frozen storage and demonstrated that tea catechins are effective alternatives to vitamin E as natural dietary antioxidants. PMID- 22061510 TI - Absorbance of light by mitochondria in pork muscle fibres differing in myoglobin content. AB - A scanning microscope photometer was used to map the transmittance (T) of white light along short lengths (?1 mm) of muscle fibres in transverse sections of pork psoas minor (n=8, Duroc*Yorkshire, hot carcass weight 86.1+/-5.2 kg). Red fibres (high myoglobin) were compared with white fibres (low myoglobin; n=16 pairs; 60.1+/-28.1 h post-mortem). Raster scans across cut ends of fibres were eroded in concentric zones to find radial gradients of T. All red fibres had positive radial gradients (mean T mm(-1)=5.389+/-3.680) from outer to inner zones, showing T was higher (P<0.01) in the axis relative to the periphery. White fibres had either positive or negative gradients (mean T mm(-1)=0.394+/-2.546). Gradients in red fibres were higher (P<0.001) than in white fibres. Radial gradients matched the visible distribution of mitochondria. It was concluded mitochondria dominate over myofibrils in giving red fibres lower T than white fibres, adding to other effects from myoglobin and pH. Whether or not mitochondrial effects are visible in pork displayed for retail sale remains to be determined. PMID- 22061511 TI - Quality characteristics of loaves from buffalo meat, liver and vegetables. AB - The present investigation explored the possibilities of commercial utilization of buffalo liver in comminuted meat products. In this study, the effect of incorporating liver with meat and vegetables in loaves was studied. Different types of loaves were evaluated: (1) Control meat loaf, (2) liver-meat loaf (20% liver) and (3) liver-vegetable loaves (40% liver, 1:1 ratio of carrot and potato). The pH's; yield's, emulsion stabilities and proximate compositions were not significantly different between meat and liver-meat loaves. However, liver vegetable loaves gave significantly (P<0.05) lower yields and different proximate compositions. Although, liver-meat and liver-vegetable loaves had acceptable sensory scores (above 6), control meat loaves gave significantly (P<0.05) higher sensory scores. Instrumental color evaluation suggested significantly (P<0.05) higher redness (a(*)) and chroma values in meat loaves and significantly (P<0.05) higher values of brightness (L(*)), yellowness (b(*)) and hue values in liver meat and liver-vegetable loaves. Texture profile analysis showed that liver-meat and liver-vegetable loaves had significantly (P<0.05) lower values of hardness, springiness, cohesiveness, gumminess and chewiness than the control meat loaves. Among the loaves, liver-vegetable loaves were softer and hence had lower values for the textural parameters than liver-meat loaves. During refrigerated storage, liver-vegetable loaves had significantly (P<0.05) lower thiobarbituric acid reacting substances (TBARS) values than meat and liver-meat loaves. Shelf life studies indicated a shelf life of 15 days for meat and liver-meat loaves and 10 days for liver-vegetable loaves at 4+/-1 degrees C. It was concluded that buffalo liver could be commercially utilized for the preparation of acceptable comminuted meat products. PMID- 22061512 TI - Effect of diet finishing mode (pasture or mixed diet) on antioxidant status of Charolais bovine meat. AB - The aim of this study was to better understand the effect of diet finishing mode (pasture or mixed diet) on the antioxidant status of bovine meat (M. Longissimus dorsi). Effects of sex (cow, heifer and steer) and age (only in cows) were also studied. Vitamin E content of muscle and activity of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (Cat) and glutathione peroxidase (GPx), were measured. Total antioxidant status was also estimated by measuring Trolox equivalent antioxidant capacity (TEAC) and benzoate hydroxylation. Vitamin E content was higher in meat from pasture-finished animals than from mixed diet finished animals. Diet had also an important effect on antioxidant enzyme activity. Pasture finishing mode increased SOD activity and decreased GPx activity in muscle. Effect of diet on catalase activity was less pronounced. Total antioxidant status measured by benzoate hydroxylation was higher in the mixed diet-group but no effect of diet was observed on TEAC measurement. Effect of sex was observed on SOD and catalase activity and also in benzoate hydroxylation. Effect of age was only noticed on benzoate hydroxylation. PMID- 22061513 TI - The effects of irradiation on quality of injected fresh pork loins. AB - A comparison of irradiation effects on injected and uninjected fresh pork loin quality was conducted. Sixty pork loins from pigs of similar genetics were obtained from a pork harvesting facility immediately prior to processing. Thirty loins were injected with a brine composed of 2.17% salt/3.04% phosphate/20.8% lactate brine while thirty were not injected. Injected loins were pumped to 13% added weight. Ten loins of each group of thirty were not irradiated while an additional 10 loins were irradiated at 2.2 kGy and the final ten loins were irradiated at 4.4 kGy. Lipid oxidation, color, purge, volatiles, and tenderness were measured on sections of the treated loins after 0, 7, 21, and 35 days of refrigerated storage. Lipid oxidation was minimal for the 0 and the 2.2 kGy treated loins, but was significantly greater (P<0.05) at day 35 for the loins treated with 4.4 kGy. Warner-Bratzler shear (WBS) force measurements were significantly lower (P<0.05) for the injected loins, but irradiation did not have an effect on shear force. Purge was significantly lower for the uninjected loins irradiated at 2.2 kGy than for those irradiated at 0 and 4.4 kGy. The injection treatment did not alter the effects of irradiation on the quality characteristics measured. PMID- 22061514 TI - The effect of cooling rate on beef tenderness: The significance of pH at 7 degrees C. AB - To study the effects of cooling regime on beef tenderness, seven commercial beef slaughterhouses with different cooling regimes were selected to obtain different carcass cooling rates. The pH values and temperatures of 8 M. longissimus dorsi (LD) and M. semimembranosus (SM) muscles from each slaughterhouse were monitored for 30 h. The muscles of the monitored carcasses were excised and vacuum packed for Allo-Kramer shear force (SF) determinations. Samples were kept at 3-4 degrees C for 5 or 21 d. The slaughterhouses were grouped by their average pH values of the muscles, prevailing at the moment when the temperature of the muscles reached 7 degrees C. The pH groups for LD were (i) low (5.52-5.63), (ii) medium (5.84-5.97) and (iii) high (6.16-6.17). The highest shear forces were in group (iii), being the toughest: 155-152 N/g, and the lowest in group (i) (the most tender): 108-116 N/g, respectively. The regression equation or the shear force was SF=-295.4+73.0*(pH at 7 degrees C); (R(2)=87%). There was no significant correlation between the cooling rate and tenderness in SM, indicating that it is difficult to control the tenderness of all muscles using the same cooling regime. The ageing effect was more marked and the variation in the shear forces smaller in the slaughterhouses generating carcasses with low pH values at 7 degrees C than in those generating high ones. It was concluded that a low cooling rate, or more specifically, the temperature/pH at the onset of rigor mortis, is important for beef tenderness. The pH of LD must fall to values below 5.7 before/when the temperature reaches 7 degrees C. PMID- 22061515 TI - The effects of RN genotype and tumbling on processing yield in cured-smoked pork loins. AB - The objective was to investigate the effects of RN genotype and tumbling treatment on yields throughout the processing of cured-smoked loins. Furthermore, the economic outcome was calculated for the different treatments because the technological yield is important for the meat industry. The study comprised two separate trials, T1 and T2, and included loins from 62 and 32 female pigs crossbreed with Hampshire, respectively. All loins in T1 were tumbled, whereas half of the loins in T2 were tumbled and the remainder was non-tumbled. Glucose and glucose-6-phosphate concentrations in meat juice and drip loss were higher, and ultimate pH and technological yield lower in loins of the RN(-) carriers than those of non-carriers. Water loss during processing was largest at heating, when yield between RN genotypes differed the most for T2. Yield between genotypes differed the most at curing for T1. When tumbling was included in the processing the technological yield increased, but the RN allele was still negatively affected. Salt content in cured-smoked loins was higher in non-carriers than RN( ) carriers in T1, whereas salt content in non-tumbled non-carriers was significantly lower than in the other cured-smoked loins in T2. Tumbled cured smoked loins contained more water than non-tumbled loins. There were moderate to high correlations between ultimate pH and processing yields except for curing yield. Water content in the cured-smoked loins was positively related to technological yield. The differences between the two trials suggest that the process design greatly influences the final product. PMID- 22061516 TI - Myofibrillar 1-D fingerprints and myosin heavy chain MS analyses of beef loin at 36 h postmortem correlate with tenderness at 7 days. AB - This study investigated the potential for relating changes in electrophoretic protein patterns derived from the longissimus dorsi of beef cattle 36 h postmortem with tenderness at 7 days. We report finding a significant correlation (R(2)=0.82) between electrophoretic l. dorsi myofibrillar fingerprints at 36 h postmortem and tenderness at 7 days, as determined by Warner-Bratzler shear analysis. In addition, we have used mass spectrometric analyses to identify fragments of bovine myosin heavy chain that are significantly correlated with tenderness. Furthermore, this method offers the potential to increase our understanding of the fundamental cellular mechanisms underlying the proteolytic breakdown of muscle proteins during the aging process. PMID- 22061517 TI - Changes of the fatty acid composition and malondialdehyde concentration in rabbit Longissimus dorsi muscle after regular electrical stimulation. AB - The experiment was carried out to investigate, whether in vivo transcutaneous electrical nerve stimulation (TENS) affects the fatty acid composition and antioxidant status of rabbit Longissimus dorsi muscle. Altogether 20 Pannon White meat type rabbits were divided into two groups, from which one was routinely exposed to TENS treatment with the following settings: 2 events (each 20 min) a day/50 days, 1 channel (2 electrodes)/animal, 30 Hz, 20 MUs impulse length and 10 mA. The control group was not treated. After slaughtering gas chromatography analysis of the muscle showed significantly decreased stearic, arachidonic and docosahexaenoic acid proportions, while the estimated activity of the elongase enzyme decreased. The malondialdehyde concentration decreased insignificantly in the treated group, however, it followed the changes of the total highly unsaturated fatty acid amount (three or more double bonds), which decreased from 9.16% to 7.81%. The adaptation to the in vivo electrical treatment may significantly influence the meat fatty acid profile, especially PUFA proportion. PMID- 22061518 TI - Up- and down-regulation of longissimus tenderness parallels changes in the myofibril-bound calpain 3 protein. AB - The objective of this study was to utilize Ca(2+) and Zn(2+) treatments of meat to critically explore the possible role of calpain 3 in meat tenderisation. Calpains 1 and 2 were also examined for comparative purpose. Control animals plus animals infused with CaCl(2), ZnCl(2) or H(2)O were used (six lambs per treatment) to determine the temporal changes in muscle calpain 3 protein in the Longissimus thoracis et lumborum (LTL) during post-mortem storage. Concurrently, the temporal changes of; (1) shear force, (2) sarcomere length, (3) proteolysis of titin and nebulin and (4) calpains 1 and 2 proteins were also determined. Infusing LTL with Ca(2+) or Zn(2+) caused significant up- and down-regulation of LTL tenderisation, respectively, compared to water infusion and the control animals. Furthermore, the rate of breakdown of calpain 3, the rate of proteolysis of titin and nebulin and the rate of meat tenderisation during post-mortem storage of LTL in the various treatments were highly correlated. These studies suggest that calpain 3, like calpain 1, may be involved in the tenderisation of meat through limited proteolysis of specific muscle structural proteins such as titin and nebulin. PMID- 22061519 TI - Growth and production of volatiles by Staphylococcus carnosus in dry sausages: Influence of inoculation level and ripening time. AB - Three sausage batches inoculated with normal inoculation level of Pediococcus pentosaceus (5*10(6) CFU/g) and with low, intermediate, and high inoculation levels of Staphylococcus carnosus (10(5), 5*10(6), 5*10(7) CFU/g, respectively) were produced. Cell counts and formation of volatiles were followed throughout a ripening period of three weeks. The staphylococci exhibited the fastest growth in sausages with a low inoculation level, whereas growth was only moderate in sausages with a high initial level. Analysis of volatiles showed that methyl branched aldehydes and acids, phenylacetaldehyde, 2-methyl-1-butanol, dimethyldisulphide and dimethyltrisulphide were produced in higher amounts in sausages with a high inoculation level of S. carnosus, whereas a low inoculation level correlated with high amounts of diacetyl, ethanol and ethyl esters. The levels of most compounds increased over time, but the amount of diacetyl was negatively correlated to ripening time. A negative interaction effect between inoculation level and ripening time was observed for the amounts of methyl branched aldehydes. PMID- 22061520 TI - Extensively reared Iberian pigs versus intensively reared white pigs for the manufacture of liver pate. AB - Physico-chemical characteristics and quality traits of the raw ingredients (muscle cuadriceps femoris, liver and adipose tissue) and the pates made from extensively reared Iberian pigs and intensively reared white pigs, were evaluated. The differences found between muscles, livers and adipose tissues from Iberian and white pigs influenced the characteristics of the pates. Compared to pates from white pigs, pates from Iberian pigs had a higher content of heme iron (27.5 MUg/g vs 11.5 MUg/g; p<0.05) and lower content of non-heme iron (27.5 MUg/g vs 33.7 MUg/g; p<0.05). Pates from Iberian pigs exhibited a darker colour (L (*):18.6 vs 15.9, p<0.05) with less redness (a (*) values: 9.1 vs 11.3; p<0.05) and yellowness (b (*) values: 13.1 vs 14.8, p<0.05). Thus, pates from white pigs had higher values of chroma (18.6 vs 15.9, p<0.05) and smaller values of hue (52.5 vs 55.2, p<0.05) that those from Iberian pigs' pates. In fatty acid composition, pates from white pigs had higher proportions of SFA (37.9% vs 32.8%, p<0.05) and PUFA (14.4% vs 9.6%, p<0.05) than pates from Iberian pigs and lower percentages of oleic (53.4% vs 43.6%, p<0.05) and total of MUFA (57.5% vs 47.6%, p<0.05). Pates from Iberian pigs had a lower n-6/n-3 values (13.2 vs 17.2; p<0.05). PMID- 22061521 TI - Fattening performance, carcass traits and meat quality characteristics of calves sired by Charolais, Simmental and Eastern Anatolian Red sires mated to Eastern Anatolian Red dams. AB - Comparisons were made among calves sired by Charolais (C), Simmental (S) and Eastern Anatolian Red (EAR) breeds of bulls for fattening, carcass and meat quality traits when mated to EAR dams. C- and S-sired calves had 43.1% and 36.4% higher daily weight gain, 44.5% and 43.9% heavier final weight in fattening, respectively. Calves produced by C sires had best feed efficiency value (6.51 vs. 7.44 and 7.22) compared to the S and EAR sire breed groups. Carcasses of C- and S sired calves had heavier weight, higher dressing percentage and greater Longissimus dorsi (LD) muscle area than those of EAR-sired calves. USDA yield grades were lower (P<0.01) for carcasses from C and S sires, and highest for carcasses from EAR calves. C-sired calves received higher (P<0.01) ratings for panel tenderness score, lower shear force value and number of chews before swallow than S- and EAR-sired progeny. Overall results of the study suggested that fattening performance, carcass and meat quality characteristics might be considerably improved by using C sires in the crossbreeding program as sire breed. PMID- 22061522 TI - Risk assessment of PSE condition due to pre-slaughter conditions and RYR1 gene in pigs. AB - A polychotomous logistic regression model was used to identify and assess the risk factors for pork meat becoming pale, soft and exudative (PSE). A total of 116 deliveries, comprising 15,695 commercial pigs delivered from different commercial farms to five Spanish pig commercial abattoirs were surveyed. The PSE condition was described as an ordinal response variable (normal, prone to PSE and PSE) based on measurements of electrical conductivity in the Semimembranosus muscle 1-2 h post-mortem. The RYR1 genotype, the abattoir, the season, the gender, the floor surface in the lorry, the loading system, and the stocking density during transportation influenced the risk of PSE condition, as well as on farm fasting time, loading time, transportation and lairage times. The effect of the RYR1 gene, determined in a subsample of 1331 pigs, was due to nn stress susceptible pigs, in which the risk of PSE meat (PQM>6 MUs) increased fourfold. Abattoirs should be especially careful in summer, when the risk of PSE meat was found to be double that of winter. The risk of PSE meat decreased with the time of transportation, though its effect depended on the stocking density. Thus, our results indicate that, for transits longer than 3 h, the risk of PSE increases with stocking density during transport, while the opposite occurs for shorter transits. PMID- 22061523 TI - Effect of feed restriction on rabbit meat quality of the Rex du Poitou((r)). AB - Two orylag((r)) rabbit genotypes, Castor and Chinchilla, feed restricted from 8 to 18 weeks of age at 130 g/d or fed ad libitum, were compared for growth, feed efficiency, carcass traits, and meat sensory characteristics. The total body electrical conductivity (ToBEC) value was also measured to predict meat quality. The feeding level was more restrictive for Castor than for Chinchilla rabbits (74% and 90%, respectively). As expected, growth, feed efficiency, carcass yield and adiposity were altered in both genotypes with feed restriction. For restricted animals, tenderness, juiciness, flavour, flouriness, stickiness and fatness were not affected by the genotype. Feed restriction only significantly decreased flouriness in the Castor genotype. Correlations between meat characteristics and sensory traits were low, and the ToBEC value was not correlated with organoleptic quality. PMID- 22061524 TI - Development of an n-3 fatty acid and alpha-tocopherol enriched dry fermented sausage. AB - Five batches of "salchichon", which is a dry fermented Spanish sausage, were manufactured using backfat and meat enriched in polyunsaturated n-3 fatty acids and alpha-tocopherol. Raw materials were obtained from animals fed on diets of the same ingredients with the exception of the oil source [sunflower oil (batch control, C), linseed oil (L and LE), 1/1 (w/w) linseed and olive oil (LO and LOE)] and alpha-tocopherol quantity [20 mg/kg diet of alpha-tocopherol (C, L and LO) or 200 mg/kg diet of alpha-tocopherol (LOE and LE)]. A final product with a healthier polyunsaturated fatty acid n-6:n-3 ratio (< 4) was obtained from all linseed oil-enriched batches as compared with the control (12). The batches of sausages manufactured with backfat and meat from animals fed on diets enriched in alpha-tocopherol and linseed, or linseed and olive oil with or without alpha tocopherol supplementation show a higher lipid oxidative stability than those of diets enriched in linseed oil without alpha-tocopherol supplementation. Sausages of dietary treatment C, LE, LO and LOE did not show differences in water, protein, fat and ash contents, a(w), pH, texture profile analysis and sensory features (odour, colour, texture, juiciness and taste quality). Sausages manufactured with material from animals fed on linseed oil-enriched diets and no added alpha-tocopherol (L) showed an unfavourable rancidity degree detected by both 2-thiobarbituric acid-reactive substances (TBARs) index and sensory panel. PMID- 22061525 TI - Effect of the fungal protease EPg222 on the sensory characteristics of dry fermented sausage "salchichon" ripened with commercial starter cultures. AB - The effect of the addition of the fungal protease EPg222 on the sensory characteristics of dry fermented sausage "salchichon" ripened with commercial starter cultures was investigated. Sausages were prepared with purified EPg222 and Staphylococcus carnosus, Staphylococcus xylosus, and Lactobacillus sakei as starter cultures, ripened for 145 days and compared with a control batch only inoculated with the starter cultures. Dry fermented sausages ripened with EPg222 and starter cultures showed higher amount of NPN and volatile compounds derived from amino acid catabolism, than control ripened only with starter cultures. Several branched aldehydes, acids and alcohols such as 2- and 3-methylbutanoic acid and 2-methylpropanol were detected only in enzyme treated samples. Sensory analysis reflected higher values for aroma intensity of sausages treated with EPg222 and lower values of hardness than control. The effect of EPg222 may be of great interest to improve sensory characteristics of dry fermented sausages ripened with starter cultures. PMID- 22061526 TI - Ohmic processing: Electrical conductivities of pork cuts. AB - Efficacy of ohmic processing can be influenced by the conductivities of individual components within the food and their behaviour and interactions during the heating process. This study relates to the determination of electrical conductivities of a selection of pork meat cuts used in meat processing. Conductivity measurements of pork cuts indicated that lean is highly conductive compared to fat and addition of fat to lean reduced the overall conductivity but the addition of fat over the range (i.e. 0-100%) was non-linear. Light microscopy suggested that differences in the conductivities of leg and shoulder lean (entire) (0.76 vs. 0.64 Sm(-1), respectively) could be due to the denser muscle fibre structure and/or higher intra-muscular fat in shoulder vs. leg. This could be of significance for ohmic processing of full muscle products. PMID- 22061527 TI - Effect of pasture finishing on the meat characteristics and intramuscular fatty acid profile of steers of the Rubia Gallega breed. AB - The Rubia Gallega cattle breed is the most important stock for beef production in Spain. A study about the influence of feeding systems on beef quality is needed. Comparison of the effect of a pasture finishing system and an indoors finishing system (maize silage and concentrate) on the meat quality and intramuscular fatty acid profile of Rubia Gallega steers (slaughter age 30 months) was determined using samples of Longissimus thoracis muscle. There were no differences between treatments in meat pH, drip loss, water holding capacity, cooking loss and muscle colour. Meat from pasture-fed steers was more tender than meat from indoors finished ones at 24 h post-mortem, but differences disappeared at 7 days. Subcutaneous fat of grass-fed steers showed higher yellowness at 24 h and 7 days post-mortem and lower brightness at 7 days post-mortem than indoors finished ones. Intramuscular fat of indoors finished steers presented higher concentrations of C18:2 and a less favourable ratio of n-6/n-3 polyunsaturated fatty acids than pasture finished steers. PMID- 22061528 TI - Fatty acids, antioxidants and oxidation stability of processed reindeer meat. AB - The effect of hot smoking and drying on reindeer meat (M. semimembranosus) was investigated with regard to vitamin content, fatty acids (FA), lipid oxidation and lipolysis. In smoked and dried meat, free fatty acids were found to increase (P<0.001), whereas polar lipids, cholesterol and triacylglycerols decreased. Only slight changes in FA composition of the smoked meat were found but the composition of the dried meat differed significantly from both smoked and fresh meat. Fresh and smoked meat were found to have low values (0.11 MUg/g dry matter (DM); 0.21 MUg/g DM) of thiobarbituric acid reacting substances but dried meat had high values (8.33 MUg/g DM; P<0.001). Retinol was found only in the fresh meat and the tocopherol content decreased significantly (P<0.001) as a result of the processing. We conclude that the smoking process slightly changed FA composition, lipid class composition and vitamin content, whereas drying resulted in major changes in all the analysed parameters. PMID- 22061529 TI - Histochemical properties of fibre types in muscles of wild and domestic pigs and the effect of growth rate on muscle fibre properties. AB - This study reports the results of a comparison of the histochemical properties of various types of porcine muscles in wild and domestic pigs. In domestic pigs, the influence of growth rates on these properties were studied in five muscles: longissimus dorsi (LD), semimembranosus (SM), gluteus superficialis (GS), infra spinam (IS) and masseter (MAS). The growth rate was expressed as: (i) live weight (LW) at 165+/-2 days and (ii) daily LW gain from day 88 to day 165 (DG) on the experimental diet. LD, SM, GS and IS of wild pigs were found to contain a higher area percentage of oxidative type IIA fibres (type IIA%(area)) and a lower percentage area of glycolytic type IIB fibres (type IIB%(area)) than the same muscles of domestic pigs. The capillary density in the light muscles (LD, SM, GS) of wild pigs was twice that of domestic pigs, indicating higher oxidative capacity. In domestic pigs the cross sectional area of type IIB fibres (CSA(IIB)) was markedly larger than the cross sectional area of type I (CSA(I)) and IIA (CSA(IIA)) fibres. The average fibre cross sectional area (CSA(fibre)) was about the same in the muscles of wild and domestic pigs except in LD and SM, where the average fibre cross sectional area was approximately 25% smaller in wild pigs than in domestic pigs. This difference was caused by the large cross sectional area of type IIB fibres in the light muscles of domestic pigs. In the light muscles of domestic pigs, the cross sectional area of type IIA fibres increased most with increasing growth rate. Growth rate influences muscle fibre properties only in light muscles, not in dark muscles. PMID- 22061530 TI - A comparison of fat composition of Japanese and long-term grain-fed Australian steers. AB - Subcutaneous and intermuscular fat samples were collected from carcases of four major breeds of steers in Japan: Wagyu, Wagyu * Angus, Dairy and Murray Grey. For comparison, we also collected subcutaneous fat samples from carcases of long-term grain-fed (350-455 days) Angus, Jersey and Angus * Hereford steers, and short term grain-fed (70-100 days) Murray Grey steers in Australia. Fatty acid profiles were determined on all samples and triacylglycerol composition, thermal properties, fat cell size and lipid and connective tissue contents were determined on representative samples. Compared with the Japanese samples which were soft to very soft when assessed subjectively, samples of Australian fat were generally hard and somewhat fibrous in appearance. These tactile and visual differences in the hardness of the subcutaneous fat between the Japanese and Australian beef were confirmed by the physical and chemical properties determined. Markedly different melting patterns were observed for the Australian and Japanese fat samples. The Japanese fat had considerably less saturated and more unsaturated fatty acids resulting in much higher unsaturated/saturated ratios (1.9) compared with the Australian samples (1.0). This resulted primarily from the high contents of oleic and palmitoleic acids and the low content of stearic acid of the Japanese samples. The triacylglycerols from the Japanese fat had considerably less tri-saturated and di-saturated fatty acids and more di monounsaturated and tri-monounsaturated fatty acids in their structure. Differences were observed when the Japanese subcutaneous fat samples were grouped by their meat quality grades. From Grade 5 to Grade 2, there was a significant decrease in marbling score (9.3 to 2.5) and in the ratio of palmitoleic to stearic acid (1.7 to 1.2) and an increase in the connective tissue content (1.5 to 2.1%). Compared with subcutaneous fat, intermuscular fat had a higher content of saturated and a lower content of unsaturated fatty acids resulting in a lower ratio of unsaturated to saturated fatty acids and of palmitoleic to stearic acid. It was concluded that the fatty acid composition and the triacylglycerol structure of fat plays the predominant role in determining the lustre, texture and properties of fat desired by the Japanese market: the soft character of fat from Japanese cattle results primarily from its low content of stearic acid and consequent lower melting temperatures. Fat cell size and the lipid and connective tissue contents of fat appear to be less important. PMID- 22061531 TI - Pre-cure freezing affects proteolysis in dry-cured hams. AB - Several parameters (sodium chloride, moisture, intramuscular fat, total nitrogen, non-protein nitrogen, white precipitates, free tyrosine, L* a* b* values and acceptability) related with proteolysis during the curing were compared in dry cured hams manufactured from refrigerated and frozen/thawed raw material. Pre cure freezing increased the proteolysis levels significantly (p<0.05) in the zones of the ham where water losses and absorption of salt is slowest. Frozen hams present a high incidence of white precipitates, formed mainly by tyrosine crystals. The colour and acceptability scores are similar in frozen and refrigerated hams. The previous freezing and thawing process accentuates the water losses, salt absorption and proteolysis of the cured meat, although it does not significantly affect the sensory quality of the dry-cured ham. PMID- 22061532 TI - Effect of content of protein, fat and modified starch on binding textural characteristics, and colour of comminuted scalded sausages. AB - The effects of modified potato starch addition-distarch phosphate (ranging from 3.32 to 5.68%) and varying levels of fat and protein (ranging from 11.6 to 28.4% and from 7.32 to 10.68%, respectively)-on comminuted scalded sausage quality characteristics were investigated. Sausage quality was determined by measuring textural, hydration and colour characteristics. Starch addition favourably affected WHC and cooking loss and increased hardness of sausages processed. Fat reduction resulted in an increase in cohesiveness, gumminess and chewiness values, which were not overcome by the added starch. Lower fat contents were also accompanied by a significant reduction in the cooking yield and WHC. Protein content was the variable that most influenced WHC, hardness, gumminess and chewiness. Sausage colour parameters were affected only by varying fat levels (L*, a*, b*) and protein content (L*, a*). PMID- 22061533 TI - Estimation of chemical carcass composition from 8th rib characteristics with Belgian blue double-muscled bulls. AB - Characteristics from the 8th rib cut: chemical composition, tissue composition after dissection, specific gravity (SG) and m. longissimus thoracis (LT) composition, collected on 17 Belgian Blue double-muscled fattening bulls were used to generate equations for predicting chemical carcass composition. Carcass composition was best predicted from chemical analysis of the 8th rib cut and the empty body weight (EBW) of the bull. Carcass chemical fat content (CCF, kg) was predicted from the 8th rib cut fat content (ether extract, 8RF, kg) by the following regression: CCF=1.94+27.37 8RF (R(2)=0.957, RSD =9.89%). A higher coefficient was found for carcass water (CCW, kg) predicted from 8RF and EBW: CCW=-2.26+0.28 EBW-34.28 8RF (R(2)=0.997, RSD=1.48%). No parameter was found to improve the prediction of CCP from EBW solely: CCP=-0.86+0.08 EBW (R(2) =0.992, RSD=2.61%). Prediction equations based solely on LT composition had low R(2) values of between 0.38 and 0.67, whereas no significant equations were found using SG. However, equations based on EBW had R(2) values between 0.78 and 0.99. Chemical components of the 8th rib cut in combination with EBW are most useful in predicting the chemical composition of the carcass of Belgian-Blue double-muscled bulls. PMID- 22061534 TI - Effects of high-intensity high-frequency ultrasound on ageing rate, ultrastructure and some physico-chemical properties of beef. AB - High-intensity and high-frequency ultrasound was tested for its ability to accelerate meat ageing and increase beef tenderness. Samples (~50g) of semimembranosus muscles from 8 cull cows were assigned to ultrasonic treatment (2.6MHz; 10W/cm(2); 2 *15s) either pre-rigor (day 0, pH 6.2) or post-rigor (day 1, pH 5.4). When applied pre-rigor, ultrasound induced a slight delay in rigor mortis onset, a stretching (12-15%) of the sarcomeres (p<0.05), an ultrastructural alteration in the Z-line region and an immediate increase (around 30%) in the release of calcium in the cytosol (p<0.05). However, no conclusive effect on meat ageing rate was observed. Post-rigor ultrasonic treatment did not induce any structural modification but slightly improved the ageing index after 6 days (p<0.05). However, no improvement in the final (day 14) ageing index was observed compared to the controls. As ultrasound had also no effect on the thermal stability of collagen, at both postmortem times, no improvement in meat tenderness can be expected under the conditions used. PMID- 22061535 TI - The influence of added whey protein/carrageenan gels and tapioca starch on the textural properties of low fat pork sausages. AB - Response surface methodology (RSM) was used for simultaneous analysis of the effects of added high gelling 35% whey protein concentrate, (0-12%)/carrageenan (0-3%) preformed gels with dry addition of tapioca starch (0-3%), on the physical, textural and sensory characteristics of low-fat fresh pork sausages. Experimental design allowed for evaluation of potential interactive effects between these ingredients. Sausages were evaluated for cookloss, water holding capacity (WHC), mechanical texture and sensory attributes. Analysis of variance of regression models showed that ingredient blends had a significant influence on cookloss (p<0.01), WHC (p<0.05), purgeloss (p<0.05), texture (p<0.001) and the sensory attributes of flavour intensity (p<0.05), overall flavour (p<0.01) and juiciness (p<0.001). Addition of preformed gel and tapioca starch had a significant (p<0.01) negative interactive effect on % cook loss, and gave a significant (p<0.05) positive linear effect for mechanical textural values. Increasing levels of preformed gel blends with tapioca starch resulted in a general decrease in flavour intensity and overall flavour scores. Mixed gels containing high gelling 35% (protein) whey protein concentrate (8%) and carrageenan (1.5%), with dry addition of tapioca starch (3%) produced final low fat (<3% fat) pork sausages with similar characteristics to those of full-fat (20% fat) controls. PMID- 22061536 TI - Sensory characteristics of cooked pork loin as affected by nucleotide content and post-mortem meat quality. AB - Muscle longissimus dorsi excised at 2hr post mortem was utilised to study the effect of post-mortem meat quality, and their content of nucleotide metabolites, on the sensory characteristics of cooked loin. Four different post mortem meat qualities were defined: pale soft exudative (PSE), red soft exudative (RSE), red firm non-exudative (RFN) and dark firm dry (DFD). The DFD meat quality class showed low sour and salty tastes and a high sweet taste, low astringency and high juiciness and tenderness, giving the best overall quality. On the other hand, the RSE quality class produced a meat with a low juiciness and high hardness, and a low overall quality although these differences were not significant (p<0.05) against RFN and PSE meats. The effect of nucleotide metabolite contents on the sensory meat properties were most significant on taste although, the different meat qualities were only significantly different (p<0.05) in the content of hypoxanthine, guanosine, GDP and IDP. PMID- 22061537 TI - Effect of rigor temperature on muscle shortening and tenderisation of restrained and unrestrained beef m. longissimus thoracicus et lumborum. AB - Pairs of muscularis longissimus thoracicus et lumborum (LTL) from young bulls were removed within 1h of slaughter. Small portions of the muscles were placed in a rigormeter to continously follow the isometric tension and isotonic shortening developed, at constant temperatures of 15, 20, 25, 30 and 35 degrees C, as the muscle went into rigor. The bulk LTL was placed in water baths at the same temperature. One of the bulk pairs was tightly restrained by wrapping, to reduce muscle shortening, the other was unrestrained free to shorten. For the bulk samples, shear values were measured using a Warner-Bratzler instrument (1, 7 and 14 days post mortem), and sensory attributes were measured using a sensory panel (7 and 14 days post mortem). Minimum tension and shortening occurred at 15 degrees C. The activation energy for the muscle shortening process was larger than for the isometric tension process. This indicates that the isometric tension data, collected during rigor, does not solely reflect muscle shortening. Thus, a counteracting process that decreases the tension response, most likely ageing is simultaneously detected. Meat that went into rigor at 15 degrees C had least shortening and was always more tender than meat going into rigor at higher temperatures. For meat entering rigor at temperatures higher than 15 degrees C, restraining of the muscle by wrapping, significantly (p<0.05) decreased the amount of muscle shortening and resulted in an improved meat tenderness (p<0.001). It was also observed that at rigor temperatures higher than 15 degrees C the meat tenderness is affected negatively by a reduced ageing capacity. It therefore appears that muscle shortening and enzyme activity both affect tenderness and that both are highly affected by rigor temperature and have the greatest beneficial effect at a rigor temperature of 15 degrees C. PMID- 22061538 TI - Quality of pig adipose tissue: relationship between solid fat content and lipid composition. AB - The dependence of solid fat content at 20 degrees C of adipose tissues on their fatty acid and triacylglycerol compositions was studied on lipids extracted from tissues from 166 pigs. The solid fat content (SFC20) was 20% on average but varied widely (9-35%). The SFC20 variability was closely related to the proportions of disaturated triacylglycerols and more specifically to palmitoyl stearoyl-oleoyl-glycerol (R(2)=0.92). The SFC20 variability was also related to the proportions of the saturated fatty acids, palmitic and stearic acids (R(2)=0.94). The part of the variance of SFC20 explained by the proportion of polyunsaturated fatty acids was lower (R(2)=0.48). The iodine value showed a high correlation with SFC20 (R(2)=0.81) but carcass lean content was a poor indicator of the solid fat content of adipose tissues (R(2)=0.06). PMID- 22061539 TI - Release of major ions during rigor mortis development in kid Longissimus dorsi muscle. AB - Ionic strength plays an important role in post mortem muscle changes. Its increase is due to ion release during the development of rigor mortis. Twelve alpine kids were used to study the effects of chilling and meat pH on ion release. Free ions were measured in Longissimus dorsi muscle by capillary electrophoresis after water extraction. All free ion concentrations increased after death, but there were differences between ions. Temperature was not a factor affecting ion release in contrast to ultimate pH value. Three release mechanisms are believed to coexist: a passive binding to proteins, which stops as pH decreases, an active segregation which stops as ATP disappears and the production of metabolites due to anaerobic glycolysis. PMID- 22061540 TI - Meat quality of wether lambs grazed on either saltbush (Atriplex nummularia) plus supplements or lucerne (Medicago sativa). AB - The meat quality of 42, 8 month-old cross-bred wether lambs that had been grazed on either predominantly saltbush (Atriplex nummularia) and supplemented with pasture hay (n=14) or oat grain (n=14) for 68 days was compared to lambs grazed predominantly on lucerne (Medicago sativa; n=14). The lambs used in the study ranged in un-fasted liveweight from 44.5 to 63.6kg pre-slaughter. There was no significant (p>0.05) difference between the treatments for liveweight, but there was a significant (p<0.05) treatment effect on hot carcass weight with those from the saltbush/hay group (SH) being lighter than those from the lucerne group. When the carcass measures of fatness or m. longissimus thoracis et lumborum area were adjusted to a common carcass weight of 22.4kg there was no difference between groups. There were no significant differences (p>0.05) between groups for pH or colour values (where L* indicates relative lightness, a* indicates relative redness and b* indicates relative yellowness). There was no significant difference (p>0.05) between groups for b(2)* values of subcutaneous fat. Treatment had a significant effect on aroma strength (p<0.05), samples from lambs in the SH group (n=10) and those in saltbush/grain (SG) group (n=10) having a stronger aroma than those from lambs grazed on lucerne (L; n=10). No treatment effect for liking of aroma was found. Flavour strength was not significantly (p>0.05) stronger for samples from groups SH and SG than for samples from group L. There was no effect of treatment on tenderness or juiciness and overall panellists ranked the samples similarly for acceptability. Finishing lambs on saltbush and either supplemented with hay or grain as used in this experiment did not present any apparent meat quality problems compared to lucerne fed lambs. PMID- 22061541 TI - On-line NIR analysis of fat, water and protein in industrial scale ground meat batches. AB - Fat, water and protein contents in industrial scale meat batches were determined on-line by near infrared (NIR) reflectance spectroscopy. The NIR instrument was mounted at the outlet of a large meat grinder, and the measurements were performed in an industrial environment. Beef and pork samples, with chemical compositions of 7-26% fat, 58-75% water and 15-21% protein, were processed with hole diameters of 13mm in the grinder plate. Calibrations were made both for a combined set of beef and pork samples, and for separate sets of beef and pork samples. Validations were either done by full cross validation of the calibration set, or by bias corrected prediction of a test set. Prediction errors for the two sample sets, expressed as root mean square errors of cross validation or standard error of prediction, were in the ranges 0.82-1.49% fat, 0.94-1.33% water and 0.35 0.70% protein, depending of sample set and species of animal. The presented application is an improvement to the existing manual meat standardisation procedure, and has been implemented for regular use in a Norwegian meat manufacturing plant. PMID- 22061542 TI - Effect of pH(24), NaCl content and proteolysis index on the relationship between water content and texture parameters in biceps femoris and semimembranosus muscles in dry-cured ham. AB - The aim of the present study was to determine the effect of pH level and NaCl content on the relationship between water content and texture parameters in semimembranosus and biceps femoris muscles in dry-cured ham. The experiment was undertaken using 18 hams, selected in a commercial slaughterhouse. Half of the hams had a pH<5.7 and the rest a pH>6.2, measured in the semimembranosus muscle at 24-h post mortem (pH(SM24)). The hams were treated with 20, 50 or 80g of NaCl per kg of ham. At the end of the aging process nine samples from semimembranosus and biceps femoris muscles were dried to different levels of water content covering the range from 22.4% to 58.5%. At the end of the drying period, a Texture Profile Analysis was used to determine textural parameters. Samples from biceps femoris muscle and samples from hams with low pH(SM24) showed a higher proteolysis index (100*non-protein nitrogen/total nitrogen) than samples from semimembranosus muscle and samples from hams with high pH(SM24), respectively. The proteolysis index decreased when the added NaCl amount increased. The proteolysis index was the parameter that best explained the modifications in the relationship between water content and the texture parameters (hardness, cohesiveness and springiness) of dry-cured ham muscles and it would be considered in order to predict the texture in dry-cured ham at different drying levels. Dry cured hams with a lower proteolysis index were more prone to present harder texture at low water contents, which is typical of hams with crustiness problems. PMID- 22061543 TI - Sensory and physical characteristics of enhanced vs. non-enhanced meat from mature cows. AB - Semitendinosus and longissimus muscles were removed from both sides of 10 mature Simmental cows ranging from 10 to 13 yrs. After aging for 7 days, one side was injected with a commercial salt mixture to a pumped gain of 15%; the other side served as control. Muscles were aged for a further 7 days before analysis. Injection significantly increased meat pH by 0.3 units in longissimus samples and reduced shear force values from about 50N in control samples to 37N for longissimus samples and 42N for semitendinosus samples. Injection also increased juiciness and tenderness scores by approximately 1unit when assessed by a trained sensory panel using 1-8 scales. Beef flavour, however, was more atypical in injected samples, which were also more salty. Injected samples were also pinker during storage and after cooking. PMID- 22061544 TI - Deferment of slaughtering in swine affected by cutaneous erysipelas. AB - According to the European Union rules for meat inspection (Regulation (EC) No. 854/2004 of the European Parliament and of the Council of 29 April 2004, that will be enforced in January 2006 in place of Council Directive 91/497/EEC of 29 July 1991 and Council Directive 91/498/EEC of 29 July 1991), any swine carcase affected by erysipelas must be destroyed. When pigs show erysipelas during antemortem inspection, the slaughtering must be deferred. Legislation however does not specify how long should be this period. In our research, 24 swine showing cutaneous erysipelas during antemortem inspection, have been tested: 8 of them were slaughtered after 10 days, 8 after 15 days and 8 after 20 days from the observation of the disease. Skin with scars of "diamond lesions", spleen, liver, kidney, inguinal lymph nodes, tonsils and muscle samples were tested in each carcase for the presence of Erysipelothrix rhusiopathiae. The results suggest that the slaughtering of swine affected by cutaneous erysipelas must be deferred for at least 15 days from disappearance of typical lesions, in order to guarantee a good level of safety of the meat and to reduce the hazard of occupational disease for veterinarians, abattoir workers and meat processors. PMID- 22061545 TI - The effects of nitrite on the survival of Clostridium sporogenes and the autoxidation properties of the Kavurma. AB - Kavurma is a traditional cooked (fried) meat product manufactured to preserve meat. Some bacterial genera, e.g., clostridia are important in kavurma. The objective of this study was to determine the influence of nitrite and the traditional cooking process on the survival and proliferation of Clostridium botulinum and the autoxidation properties of the kavurma. For this purpose, Clostridium sporogenes having similar characteristics to C. botulinum was used, and the samples were inoculated with 10(6) CFU/g C. sporogenes cells before the traditional cooking. The final products were packaged and stored under refrigeration for 6 months, and then the oxidation parameters (TBA, peroxide and free fatty acid values) and C. sporogenes counts of samples were determined. It was observed that C. sporogenes could survive during the traditional cooking process and storage. However, counts decreased during storage; for example, nitrite containing samples initially had 3.21logCFU/g C. sporogenes and 2.73logCFU/g at the end of storage. While nitrite had a slight antimicrobial effect on clostridia, it significantly reduced the TBA, peroxide and FFA values of the samples. In conclusion, it is suggested that addition of 100ppm of nitrite might be useful in kavurma processing because of its role in limiting oxidation as well as its antimicrobial effect. PMID- 22061546 TI - Effect of modified atmosphere packaging on structural and physical changes in buffalo meat. AB - The effect of modified atmosphere packaging of buffalo meat on the structural parameters viz., fibre diameter, sarcomere length and myofibrillar fragmentation index and physical parameters viz., pH, drip loss and colour scores were studied. The buffalo meat was packed under aerobic, vacuum and modified atmosphere (80% oxygen+20% carbon dioxide) and stored at 4+/-1 degrees C upto 21 days. The results obtained revealed that vacuum-packed buffalo meat had the lowest fibre diameter and myofibrillar fragmentation index and the highest sarcomere length, vacuum thus appears to enhance ageing. Buffalo meat packed in modified atmosphere had a low drip loss and a desirable colour. The modified atmosphere packed and vacuum-packed buffalo meat was acceptable for upto 14 days at 4+/-1 degrees C. PMID- 22061547 TI - Effects of goat milk or milk replacer diet on meat quality and fat composition of suckling goat kids. AB - The effects of a diet with goat milk "GM" or milk replacer "MR" on the meat quality and fat composition of suckling Murciano-Granadina kids were studied. MR consisted of powdered skimmed milk, coconut oil and fat, and cereal products and by-products. Raw meat quality (moisture, protein, lipids, ash, collagen, cholesterol, haem pigments, CIELab colour, pH and water retention capacity), fatty acid "FA" composition and eating quality of cooked meat (odour, flavour and texture) were determined. Diet had only a slight effect on raw meat quality but had a pronounced effect on fatty acid composition and eating quality of cooked meat. MR diet increased the water/protein proportion in the muscle. The saturated/unsaturated FA ratio in GM and MR fat was 0.94 and 2.27, respectively. The major FA in GM and MR fat were C16:0 and C18:1, respectively. Short-chain C4 C12 hardly accumulated in the adipose tissue of suckling kid, increasing the relative percentages of C14-C20. This effect was more pronounced in MR fat, due to the fact that MR contained more short-chain fatty acids than GM. MR diet gave cooked meat a more intense characteristic goat meat odour and flavour, more tenderness and more juiciness than the natural suckling diet. This fact could be related to differences in meat and fat composition. PMID- 22061548 TI - The p-nitroaniline test to asses the bacterial microbiota of raw ground meat aerobically stored. AB - The previously developed p-nitroaniline test for assessing the microbial load of meat surfaces has been now adapted to determine the microbial quality of raw ground meat. A good correlation (r=0.91) between bacterial count determined by the pour plate method and the p-nitroaniline test was obtained. The sensitivity of the new method was of the order of magnitude of 10(4)cfu/g. This method allows the assay of ground meat in approximately 2.5h, it does not require expensive equipment and the results can be interpreted both spectrophotometrically and visually. Additionally, it has been proven that the method is useful in estimating the microbial quality of raw meat irrespective of the species of Gram negative psychrotrophic bacteria prevailing in the meat during refrigerated storage. PMID- 22061549 TI - Fatty acids of lamb meat from two breeds fed different forage: concentrate ratio. AB - Lambs from two Turkish breeds, Kivircik a meat breed and Sakiz a breed used for milk and meat production, were fed a diet containing commercial concentrate and hay in the ratios of either 75:25 or 25:75. The effects on fatty acid composition were studied. After weaning (at about 8 weeks) a total of 40 male lambs (20 Kivircik, 20 Sakiz) were divided into four groups of 10 animals and fed either commercial concentrate or grass hay-based diets. The lambs were group fed indoors for 60 days. The mean intramuscular total fatty acid content of longissimus dorsi for Sakiz was lower than that for Kivircik lamb. Increasing the dried grass percentage in the ration decreased the final live weight of the lambs but intramuscular total fatty acid content increased (2088 vs. 1791mg/kg muscle, p<0.001). All n-3 polyunsaturated fatty acids were higher in muscle from lamb fed dried grass-based diets than from lambs fed concentrate-based diets whereas all n 6 were higher in the latter. Polyunsaturated:saturated ratios were higher in the latter animals; 0.26 compared with 0.16 in the lambs fed grass hay. Concentrate groups displayed a higher n-6/n-3 ratio in the same muscle, 7.11 compared with 1.28 in the lambs fed grass. Muscle from Kivircik lambs had higher concentrations of C18:2 n-6 and its metabolite C20:4 n-6 (p<0.001) and also C18:3 n-3. PMID- 22061550 TI - The use of dielectric properties and other physical analyses for assessing protein denaturation in beef biceps femoris muscle during cooking from 5 to 85 degrees C. AB - Dielectric properties of beef biceps femoris muscle were recorded during heating (5-85 degrees C) to assess their linkage to phase changes monitored by differential scanning calorimetry (DSC) and rheology. DSC indicated endotherms between 56 and 81 degrees C corresponding to denaturation of actin, collagen and myosin. Matching changes in dielectric properties (dielectric constant (epsilon') and loss factor (epsilon")) were noted at radio and/or microwave frequencies though the nature of the change differed depending upon frequency. The main observation in epsilon' was an increase above 65-66 degrees C, most likely due to fluid release on collagen denaturation. This fluid plus liquid from myosin denaturation most likely solvated ions freed during myosin denaturation which manifested as an epsilon" increase. However, it must be noted that meat structural protein denaturation is compounded with physical shrinkage which can also influence dielectric properties. Rheological parameters of beef muscle heated from 5 to 85 degrees C also displayed marked changes relating to structural protein denaturation. PMID- 22061551 TI - Difference in postmortem degradation pattern among troponin T isoforms expressed in bovine longissimus, diaphragm, and masseter muscles. AB - The postmortem degradation of troponin T (TnT) in bovine longissimus (LT), diaphragm (DP), and masseter (MS) was analyzed. A 28.3kDa (conventional 30kDa) fragment of fast-type TnT isoforms showed the highest content in both LT and DP, where a 35.4kDa isoform had the highest expression among the other fast isoforms. Meanwhile, a 26.0kDa fragment was found to be the most highly produced among the fast TnT fragments in MS, where the expression of 36.5 and 32.8kDa isoforms was higher than that of 35.4 and 34.8kDa isoforms. Thus, the compositions of both the intact TnT isoform proteins and the postmortem fragments differed among the muscles examined, indicating that each TnT isoform degrades into a specific fragment in each muscle. Among the muscles, the LT muscle showed a high extent of TnT degradation and the highest expression of fast TnT isoforms containing a taste-related peptide sequence. PMID- 22061552 TI - Effect of different Duroc line sires on carcass composition, meat quality and dry cured ham acceptability. AB - Carcasses of 399 malignant hyperthermia gene free pigs from crosses sired by three types of Duroc (Virgen de la Fuente, DU1; Diputacion de Teruel, DU2; DanBred, DU3) were analyzed for carcass and meat quality. Carcass leanness and fat parameters were measured at the last rib and at the space between the 3rd and 4th last ribs counting from the last one. Weights, pH, electrical conductivity, colour and intramuscular fat were also measured. A sample of 133 legs per cross were processed by dry-curing. The ham portion including Biceps femoris, Semimembranosus and Semitendinosus muscles was evaluated for instrumental texture and colour, biochemical and sensory analyses and acceptability (trained panel and consumers). DU3 carcasses were well conformed but lean. DU1 carcasses had a lower conformation but higher marbling. DU2 carcasses were intermediate. Dry-cured hams from DU1-sired pigs had a higher overall acceptability, although fat content influenced a consumers group negatively. Leaner DU3 hams had the lowest acceptability. PMID- 22061553 TI - Molecular and physiological characterization of natural microbial communities isolated from a traditional Southern Italian processed sausage. AB - The development of the natural microbial populations during traditional processing of the "Salame di Senise", a typical little known sausage produced in the South of Italy, was investigated by using molecular and physiological techniques for taxonomic identification and technological characterization of strains. The application of RAPD-PCR over more than 90 colonies made it possible to isolate 18 bacterial and two yeast biotypes identified by partial rDNA sequencing as belonging mainly to three species of Bacillus, three species of Lactobacillus, three species of Staphylococcus and Debaryomyces hansenii. The physiological analyses revealed that the isolates belonging to Lactobacillus genus were the most acidifying, whereas Staphylococcus strains did not develop significant proteolytic and lipolytic activities. Interestingly, some Bacillus strains produced the highest values of proteolytic and lipolytic activities. The results for the technological properties of Bacillus strains isolated from this Southern Italian sausage, made without a selected starter, suggest that Bacillus strains, always present in meat curing, could play a role in the development of texture and organoleptic characteristics of the sausages. PMID- 22061554 TI - Assessment of the antioxidative potential of dietary supplementation with alpha tocopherol in low-nitrite salami-type sausages. AB - The objective of this study was to determine the effects of dietary alpha tocopherol supplementation to pigs on the lipid stability of nitrite-reduced salami-type sausages (custom-produced for this study). Fourteen crossbred pigs were divided into two equal groups. The control group (CG) was fed a basal diet containing 34ppm alpha-tocopherol, and the experimental group (EG), a diet supplemented with 364ppm alpha-tocopherol, both for 35 days. After slaughter, salami-type sausages were produced with the addition of different nitrite levels in the curing salt (100, 50, 25 and 0ppm), ripened for four weeks, sliced, and packaged under a protective atmosphere (80 parts N(2) to 20 parts CO(2)). The packed products were stored for eight weeks under simulation of the usual conditions in self-service shelves with permanent lighting (9 degrees C, 200 lux). The sausages were regularly assessed for their oxidative status (thiobarbituric acid-reactive substances, fatty acid pattern) and the amount of alpha-tocopherol, and by sensory evaluation. In the EG sausages, alpha-tocopherol concentrations were twice as high and TBARS were lower than in the CG sausages. The alpha-tocopherol in EG prevented the loss of unsaturated fatty acids during storage. Sausages of EG containing 100ppm nitrite had the longest sensory stability. However, the biochemical parameters did not indicate that nitrite had any effect on the antioxidative potential of the sausages. PMID- 22061555 TI - Effect of frozen and dried leek on processing and quality characteristics of Greek traditional sausages. AB - Blanching of leek at boiling temperature for 1min reduced (p<0.05) the nitrate content. Freezing of leek at -18 degrees C and storage for 5 months, with or without vacuum, also reduced (p<0.05) the nitrate content, while drying at 85 degrees C for 2h and storage for 5 months, with or without vacuum, had no effect (p>0.05) on nitrate content. Frozen leek as a whole plant was unsuitable for the production of traditional sausages. The most appropriate level of dried leek for sausage production was 20g/kg of meat mixture. The nitrate content of sausages with frozen and dried leek ranged on the 7th day from 24.5+/-14 to 36.3+/-13ppm and the nitrite content from 1.4+/-0.4 to 2.6+/-1ppm. Sausages with dried leek had better (p<0.05) colour, higher (p<0.05) pH and lower (p<0.05) TBA values. Sausages with frozen and dried leek had the same (p>0.05) sensory attributes as those produced with fresh leek. Vacuum packaging affected (p<0.05) the odour of fresh sausages with frozen and dried leek and the overall acceptability of fresh sausages with frozen leek. Sausages with frozen and dried leek stored under vacuum had higher scores for sensory attributes, which were not always significant. PMID- 22061556 TI - Breed and maturity effects on Churra Galega Bragancana and Suffolk lamb carcass characteristics: Killing-out proportion and composition. AB - The aim of this work was to study the carcass killing-out proportions and carcass composition of Churra Galega Bragancana (CGB) and Suffolk sheep at 20%, 25%, 30% and 35% of maturity. Forty-eight male lambs were used, 24 CGB and 24 Suffolks from the Braganca's School of Agriculture sheep flock. Suffolk lambs had greater proportions of leg, shoulder and breast joints, but lower proportions of rib, anterior rib and neck joints. Increasing maturity caused a significant decrease in leg and shoulder proportions and an increase in chump proportion. Suffolk lambs had significantly greater muscle and significantly less subcutaneous fat and kidney and pelvic fat percentages than CGB lambs. With the increase of maturity, a significant increase in intermuscular fat and a significant decrease in bone proportion were observed. It was concluded that, under the management conditions of this work, Suffolks were preferred for meat production, since at a comparable stage of maturity they had greater proportions of expensive cuts and greater carcass lean percentage. PMID- 22061557 TI - Automatic measurement of pores and porosity in pork ham and their correlations with processing time, water content and texture. AB - Pores formed in pork ham have a significant effect on its quality. However, they are mostly characterised using manual methods with special devices. In this paper, an automatic method for pore characterisation of pork ham was developed using computer vision. To segment pores from images of pork ham, three stages of image processing algorithm were developed, i.e., ham extraction, image enhancement, and pore segmentation. From the segmented pores, the porosity, number of pores, pore size, and size distribution were measured. The statistical analysis showed that 79.81% of pores have area sizes between 6.73*10(-3) and 2.02*10(-1)mm(2). Furthermore, it was found that the total number of pore (TNP) and porosity highly negatively related to the water content of pork ham (P<0.05), and had negative correlations with the cooking and cooling time. However, for texture analysis, positive correlations were found between the pore characterisations and WBS, hardness, cohesion, and chewiness, respectively, while springiness and gumminess were negatively related to TNP and porosity. PMID- 22061558 TI - Flavour perception of oxidation in beef. AB - Lipid oxidation is a major factor in meat quality. In order to relate human perceptions of lipid oxidation, as determined by a trained taste panel, to a chemical measurement of oxidation, we studied meat from animals with a wide range of potential oxidation through differences in their PUFA composition and by displaying the meat in high oxygen modified atmosphere packs for varying lengths of time. Meat was obtained from 73 Angus- and Charolais-cross steers from different trials that had been raised on 10 different diets: grass silage (high in C18:3, n-3), cereal concentrate (high in C18:2, n-6), three diets with 3% added fat consisting of three levels of protected lipid supplement (high in C18:2, n-6 and C18:3, n-3, ratio 1:1), a control with Megalac((r)) (relatively saturated), three diets with three levels of inclusion of protected fish oil (high in C20:5 n-3 and C22:6 n-3) plus a constant amount of unprotected fish oil and a final diet with an unprotected fish oil control. The longissimus dorsi muscle was excised from the left carcass side, aged vacuum packaged for 10-13 days depending on the projects and frozen for less than eight months. TBARS and sensory analyses were performed on steaks displayed for 0, 4 or 9 days under simulated retail conditions, exposed to light in modified atmosphere packaging (CO(2):O(2); 25:75). Meat oxidation increased throughout display for each of the diets, as shown by a rise in TBARS values. This increase was not linear, differences between 0 and 4 days of display were smaller than between 4 and 9 days of display. The lowest TBARS and lowest increment occurred in the two control diets and the grass-fed animals, probably due to the more saturated fat of meat from animals fed the control diets and the higher content of vitamin E. Sensory attributes were also influenced by time of display. Positive attributes, such as beef flavour or overall liking, decreased throughout display, whereas negative attributes, such as abnormal and rancid flavours, increased. The correlations between sensory and analytical attributes were high. TBARS were a good predictor of the perception of rancidity (Spearman's rho=0.84). Panellist preferences were related to the presence of beef flavour (rho=0.93) and to the absence of abnormal (rho=-0.88) and rancid flavours (rho=-0.83). Under the experimental conditions used, a TBARS value of around 2 could be considered the limiting threshold for the acceptability of oxidised beef. PMID- 22061559 TI - Meat molecular traceability: How to choose the best set of microsatellites? AB - To set up routine assays for molecular meat traceability along the food chain, the availability of a simple and low cost test for the identification of cattle carcasses is required. For this purpose, we evaluated 13 microsatellites for their ability in the identification of animals belonging to four Italian cattle breeds. Here we propose a criterion for a microsatellite-based test with the best reliability when reducing the number of loci to be analysed. The method is based on the observation that in the same loci breeds can show differences in frequencies and number of fixed alleles. This non-uniform distribution of alleles between breeds results in differences in the informative content of the same loci in different breeds. Taking into account these differences, it is possible to perform tests for the allocation of samples to specific animals utilizing a small number of microsatellites. The proposed approach allows cost reduction and ease in performing the analyses. PMID- 22061560 TI - Use of bacterial extracts to enhance amino acid breakdown in dry fermented sausages. AB - The effect of the intracellular cell-free extracts (ICFEs) of two bacterial strains (Lactobacillus sakei GO and Bacillus pumilus) on the amino acid catabolism and the sensory properties of dry fermented sausages, was investigated. Extracts were added to sausages alone or in combination with a protease, papain. Amino acid breakdown was monitored by the changes in free amino acids, ammonia and amine content during the ripening process. A 15% decrease in the content of free amino acids was observed in sausages added with the ICFE from L. sakei GO. Furthermore, the extract of L. sakei GO significantly reduced (54 68%) the content of the amino acids considered as precursors of the typical ripened flavour, i.e., valine, leucine and isoleucine. Chemical changes were not reflected in a significant improvement of the sensory quality of sausages added with the ICFEs. The potential use of the bacterial ICFEs studied in the present work for the manufacture of dry fermented sausages, and its comparison with the use of fungal extracts, are discussed. PMID- 22061561 TI - Effect of method of cooking on identification of heat processed beef using polymerase chain reaction (PCR) technique. AB - Effects of various cooking methods including boiling, roasting, pressure cooking, and pan frying on species determination of beef by PCR was studied. The meat was cooked by boiling at 97.5 degrees C for 140, 200 or 230min, by roasting at 200 degrees C for 80, 120, or 150min or by autoclaving at 120 degrees C for 30, 60, or 90min. The beef sample was pan fried until the meat was acceptable for sensory attributes (45min, meat temperature 115 degrees C, fat temp 173 degrees C) and further cooked until unacceptable. DNA was extracted from samples taken after cooking and a 271bp fragment of the mitochondrial DNA was amplified by PCR. The results indicated that with the exception of pan frying for 80min, beef was determined in all meat samples including the broth and sauce of the roasted meat. PMID- 22061562 TI - Effects of sex, weight, diet and hCG administration on levels of skatole and indole in the liver and hepatic activities of cytochromes P4502E1 and P4502A6 in pigs. AB - Cytochromes P4502E1 (CYP2E1) and P4502A6 (CYP2A6) catalyse metabolic reactions of skatole and indole metabolism. The objectives of this study were as follows: to evaluate whether activities of CYP2E1 and CYP2A6 in pigs of two live weights (LW) differ between males and females; to investigate whether activities of CYP2E1 and CYP2A6 are affected by hCG stimulation; and to investigate whether the levels of skatole and indole in the liver and the activities of CYP2E1 and CYP2A6 are affected by raw potato starch (RPS). Female pigs expressed higher CYP2A6 activity at 90kg LW, and higher CYP2E1 activity at 115kg LW compared to male pigs. Skatole levels in the liver were higher in male pigs than in female pigs at both LW, whereas indole levels were higher in males only at 115 kg LW. Neither levels of indolic compounds in the liver nor enzyme activities were affected by hCG stimulation. The inclusion of RPS in the diet reduced skatole levels in the liver in both sexes and increased CYP2A6 activity in female pigs. It was concluded that the incidence of boar taint may depend on both skatole amount, which reach the liver, and the activities of enzymes involved in skatole metabolism, which may vary depending on sex, live weight, and diet. PMID- 22061563 TI - Effect of hCG administration on the relationship between testicular steroids and indolic compounds in fat and plasma in entire male pigs. AB - Our objective was to evaluate pigs injected with human chorionic gonadotropin (hCG) as a potential model to study the effect of high testicular steroid levels on the variation in indolic compounds. Pre-selection of the sires based on their plasma skatole levels was used, to evaluate whether the response to hCG would be affected. Out of 34 entire male pigs, 17 pigs were injected with hCG and the remaining pigs were injected with sterile saline four days prior to slaughter. HCG injection increased the levels of testicular steroids (androstenone, testosterone, dehydroepiandrosterone sulphate, oestrone sulphate and oestrone; p<0.001), and indole levels in plasma and fat (p<0.05). Skatole levels in fat increased slightly but not significantly (p=0.107), whereas skatole levels in plasma were not affected. The correlation coefficients between androstenone and skatole levels in fat were 0.54 in the hCG-injected group and non-significant in the control group. Skatole levels in fat were not correlated with testicular steroids in either hCG-injected pigs or controls. Skatole and indole levels in fat were positively correlated in both groups. We concluded that hCG-injected pigs might be useful for studying factors responsible for the role of testicular steroids in the occurrence of high indole levels. Pre-selection of sires based on plasma skatole levels affected both the levels of indolic compounds and testicular steroids, especially in fat, which might have suppressed the response to hCG. Whether hCG affects skatole or not is therefore not fully elucidated. PMID- 22061564 TI - Effectiveness of rosemary essential oil as an inhibitor of lipid and protein oxidation: Contradictory effects in different types of frankfurters. AB - The effect of increasing levels (150, 300 and 600ppm) of rosemary essential oil on lipid and protein oxidation and the increase of non-heme iron (NHI) content during refrigeration (+4 degrees C/60 days) of frankfurters produced with tissues from Iberian pigs (IF) or white pigs (WF), was studied. Frankfurters with no added essential oil were used as controls. Iberian pigs were free-range reared and fed on acorns and pasture whereas white pigs (Large-white*Landrance) were intensively reared and fed on a mixed diet. Large differences were detected between types of frankfurters (Iberian vs white) in terms of fatty acid composition and tocopherols content due to the different feeding background of the animals. The effect of the addition of rosemary essential oil on the oxidative stability of frankfurters depended on the level of added essential oil and the characteristic of the frankfurter. The rosemary essential oil successfully inhibited the development of lipid and protein oxidation in IF with that antioxidant effect being more intense at higher concentrations of essential oil. In WF, 150ppm rosemary essential oil showed an antioxidant effect, significantly reducing the generation of lipid and protein oxidation products. At higher levels (300 and 600ppm) the essential oil had, in general, no effect on lipid oxidation while significantly enhanced the oxidation of proteins and the release of iron from myoglobin. The presence of certain amounts of tocopherols in the frankfurters could have influenced the activity displayed by the added essential oil leading to antioxidant or prooxidants effects though the different fatty acid composition and oxidative status between frankfurters could also have had an effect. PMID- 22061565 TI - Extensively reared Iberian pigs versus intensively reared white pigs for the manufacture of frankfurters. AB - Physico-chemical characteristics and different quality traits of the raw material (meat and adipose tissue) and the frankfurters elaborated from extensively reared Iberian pigs (IF) and intensively reared white pigs (WF) were evaluated. Hybrid frankfurters (HF) made with meat from white pigs and adipose tissue from Iberian pigs were also studied. The differences found between muscles and adipose tissues from Iberian and white pigs largely influenced the characteristics displayed by the frankfurters. Particularly remarkable are the higher amounts of substances with proven antioxidant activity such as tocopherols and phenolic compounds in tissues from Iberian pigs than in those from white pigs. No significant differences were found amongst frankfurters for their proximate composition though IF presented a higher iron content than WF and HF. IF exhibited a redder and darker colour than WF and HF. The latter were paler and showed higher hue values than IF. Concerning their fatty acid composition, IF had higher proportions of oleic acid and MUFA and smaller proportions of SFA and PUFA than WF. From a nutritional point of view, IF had a lower n-6/n-3 value than WF. The addition of adipose tissue from Iberian pigs to the HF modified its fatty acid composition compared to that of WF, significantly increasing the percentages of MUFA and reducing the proportions of PUFA, SFA and the n-6/n-3 value. Though no significant differences were found amongst frankfurters for their texture profile, a clear trend was detected, with the HF showing intermediate texture characteristics between IF and WF. PMID- 22061566 TI - A high dietary iodine increases thyroid iodine stores and iodine concentration in blood serum but has little effect on muscle iodine content in pigs. AB - There is still iodine deficiency in many populations, which justifies efforts to increase this trace element in food such as milk, eggs and meat by fortifying compound animal feeds with extra iodine. The iodine requirement of growing pigs is in the order of 100-200MUg/kg feed (as a supplement) and the effects of this dosage range or higher on pork iodine concentration should be determined including the action of relevant iodine antagonists in feed, e.g., rapeseed. In three experiments on a total of 208 pigs [Pietrain*(Landrace*Large White)] the iodine concentration of meat (m. longissimus) - 71 samples -, blood serum - 100 samples - and of the thyroid - 100 samples - was analysed by intracoupled plasma MS. In Experiment 1, 4*10 pigs received diets without or with rapeseed cake (0 and 3.2mmol glucosinolates/kg diet) either with 125 or with 250MUg iodine/kg. In Experiment 2, the three groups with 46 pigs each were fed high iodine diets (1200MUg supplementary iodine/kg) without or with 100 or 150g solvent extracted rapeseed meal/kg diet (0; 0.8 and 1.2mmol glucosinolates/kg). In Experiment 3, 3*10 pigs received either 600MUg iodine/kg feed (1) or the 5-fold dosage (600+2400MUg iodine/kg diet) administered 7 days (2) or 18 days (3) before slaughtering. The group means of pork iodine content were in the relatively small range from 3 to 16MUg/kg, which contrasted to the enormously varying dosage range from 125 to 3000MUg iodine/kg diet. There was a certain iodine dosage effect in Experiment 3 when - in comparison to the control - a 3-fold higher meat iodine concentration resulted from a 5-fold higher diet iodine concentration. In Experiment 1 with the low iodine offer, rapeseed cake with glucosinolates decreased the serum iodine level whereas in Experiment 2 this did not happen due to higher iodine fed and lower glucosinolates exposure. The thyroid iodine reflected the dietary iodine better than blood serum iodine and the serum better than muscle. However, in Experiment 2, 1200MUg iodine/kg diet produced only half the serum iodine concentration than half as much dietary iodine in Experiment 3 (600MUg iodine/kg diet), which may result from rapid elimination of blood iodine and a higher urinary excretion by longer duration of feed withdrawal before blood sampling. The muscle of pigs has to be classified as a low iodine food. Thus, there are no possibilities to concentrate this trace element reproducibly in amounts relevant for human nutrition in pork. PMID- 22061567 TI - Assessment of breed type and ageing time effects on beef meat quality using two different texture devices. AB - Forty-two male yearlings were used to assess the influence of breed type and ageing time on beef texture. Samples of the M. longissimus dorsi of four breed types [double muscled (DM), dual purpose (Brown Swiss, BS), fast growth (FG) and unimproved type (UT)] were aged for 1, 3, 7, 10, 14 or 21 days at 4 degrees C and frozen at -18 degrees C until analysed. Cooked samples (to end-point of 70 degrees C) were assessed using a Warner-Bratzler (WB) device. Raw samples were assessed using a compression device in which transverse elongation was prevented. There were no significant differences in WB values of cooked meat due to breed type, but ageing had a significant (P<0.05) on maximum load. Ageing, but not breed type, had a significant effect on the compression values of raw meat at low compression rates (P<0.001). Compression values, of raw samples, at 80% compression differed significantly (P<0.001) between breed types, but were not affected by ageing. Compression values of raw samples, at 80% compression, were affected by breed type, probably because of genotype differences in the contribution of connective tissue. PMID- 22061568 TI - Relationships between meat quality measurements in rabbits fed with three diets of different fat type and content. AB - Two hundred and eighty-four, genetically similar (a three-way cross), young rabbits were fed ad libitum, from weaning, either a commercial diet (group C, ether extract 2.6%) or a diet containing vegetable fat (group V, ether extract, 9.9%) or animal fat (group A, ether extract 11.7%). A principal component (PC) analysis was performed with the variables: ultimate pH at 24 h post mortem measured in the longissimus dorsi (LD) and in the biceps femoris (BF) muscles, colour measured on the surface of the loin, fatty acid composition of perirenal fat, meat fat content of the hind leg, water holding capacity and cooking losses of the meat, and sensory variables determined by a trained panel test. The four first PC explained 62% of the total variation (27, 13, 11 and 11%, respectively). The first PC grouped the fatty acids, the second PC grouped the sensorial variables, and the third and fourth PCs grouped the pHs and the water holding capacity. The projection of the data in the first two PCs showed three separate groups of points. Animals fed with diet V were on the left side of the graph, where the variable C18:2 lies, whereas animals fed with diets A and C lay on the right side of the graph, where the saturated acids were grouped. These were slightly separated by the higher content of oleic acid in the animals fed with diet A. The second PC, where the sensorial variables were grouped, did not separate the animals fed with diets A, V and C. The diets used in this experiment had only a slight influence on the organoleptic characteristics of rabbit meat. PMID- 22061569 TI - Use of electrical conductivity to predict water-holding capacity in post-rigor pork. AB - This study was designed to re-examine the interrelationships among ultimate pH (pH(u)), electrical conductivity (EC) and water-holding capacity (WHC), and to test if EC, using one of two EC instruments, and pH(u) can be used to predict WHC. The % drip (PD) was used as measure of WHC. Forty-seven pork loins were classified either as PSE (pale, soft, exudative), RSE (reddish-pink, soft, exudative), RFN (reddish-pink, firm, non-exudative) or DFD (dark, firm, dry), based on L* values, PD and pH(u.) The measurement of EC, conducted using the instrument developed at the University of Wisconsin-Madison (UW-EC) was highly correlated to PD at 24 h post mortem (CD=66%), but the pH (NWK) measure of EC was not as highly related to WHC as UW-EC. The predictive value of pH(u) and EC for WHC were similar. When 47 samples were divided into three different groups, such as low (< 2% drip), medium (2-6% drip) and high (> 6% drip) drip loss, UW-EC alone grouped 80% of the samples correctly. Thus, EC seemed to be an accurate predictor of WHC in pork muscle when measured at 24 h post mortem. It is conceivable that EC can be used independently, or with even better success in combination with pH(u), to classify WHC of pork carcasses. PMID- 22061570 TI - Combination of low voltage electrical stimulation and early postmortem temperature conditioning on degradation of myofibrillar proteins in Korean native cattle (Hanwoo). AB - The combination effect of low voltage electrical stimulation (LVES) and early postmortem (PM) temperature conditioning (2, 16, and 30 degrees C until 3 h PM) on degradation of myofibrillar proteins were determined from Korean native cattle (Hanwoo). Myofibrils were removed at 1, 2, 3, 7, and 14 days of PM storage (2 degrees C) and analyzed for titin, nebulin, desmin, and troponin-T by SDS-PAGE and by Western blot analysis. Degradation rate of myofibrillar proteins was affected by the combination of LVES and temperature conditioning. LVES-30 degrees C treatment resulted in faster degradation of titin, nebulin, desmin, and troponin-T during PM storage than the other treatments. Degradation of titin took place more slowly than nebulin, desmin or troponin-T. PMID- 22061571 TI - Palatability of beef steaks marinated with solutions of calcium chloride, phosphate, and (or) beef-flavoring. AB - This study evaluated the efficacy of marination for increasing consumer acceptability of beef. Top-sirloin steaks from 28 USDA select steers were randomly assigned to one of six marination treatments: control (CT), 150 mM calcium chloride (CA), 10% solution of beef-flavoring/seasoning mixture (FL), CA and FL (CF), 2.5% sodium phosphate and FL (PF), and tap water (TW). Steaks were marinated in vacuum pouches, aged for 7 days, cooked to 70 degrees C and evaluated by a trained sensory panel. Marination with CA did not affect tenderness ratings, but increased (P<0.05) bitter and metallic flavors compared to CT or TW treatments. Use of FL, alone or in conjunction with CA or sodium phosphate, increased (P<0.05) tenderness and juiciness ratings and reduced (P<0.05) bitterness and metallic flavors compared to CT, CA and TW marinades. Marination of beef, in vacuum pouches, is an effective method for increasing consumer acceptability and value beef. PMID- 22061572 TI - Combined effect of modified atmosphere bulk packaging, dietary vitamin E supplementation and microbiological contamination on colour stability of Musculus gluteus medius. AB - Ten Simmentaler type calves were fed diets supplemented with 500 mg vitamin E per day and ten fed control diets. After completion of a 100 day feeding period the cattle were slaughtered and rump steaks (M. gluteus medius) from each carcass PVC overwrapped and subsequently bulk packaged in 100% CO(2) or 20% CO(2): 80% O(2). Steaks with low levels of bacteriological contamination were also prepared and packaged. Bulk packs were stored at 4 degrees C for 0, 14, 28 and 42 days and the PVC-overwrapped samples subsequently displayed for 0, 4 and 7 days at 4 degrees C. After display saturation, surface metmyoglobin and oxymyoglobin accumulation of the steaks were determined and acceptability of the steaks assessed by sensory evaluation using a trained panel. The dietary vitamin E supplemented steaks were more acceptable than the steaks from cattle not supplemented with vitamin E. Steaks prepared with low levels of bacteriological contamination, supplemented with dietary vitamin E, were more acceptable and discoloured less than all the other treatments. Beef rump steaks bulk packaged in 20% CO(2): 80% O(2) or 100% CO(2) were acceptable and colour stable for up to 14 days bulk storage at 4 degrees C and a subsequent 2 days retail display at 4 degrees C. PMID- 22061573 TI - Beef shelf life in low O(2) and high CO(2) atmospheres containing different low CO concentrations. AB - The use of atmospheres with low concentrations of CO (0.1 to 1%), in combination with O(2) (24%), high CO(2) (50%) and N(2) (25 to 25.9%), for preserving chilled beef steaks was investigated. The atmosphere used as reference contained 70% O(2)+20% CO(2)+10% N(2). Bacterial counts showed that all atmospheres containing CO greatly reduced total aerobic population numbers, including Brochothrix thermosphacta. Lactic acid bacteria, however, were not affected. CO concentrations of 0.5-0.75% were able to extend shelf life by 5-10 days at 1+/-1 degrees C, as demonstrated by delayed metmyoglobin formation (less than 40% of total myoglobin after 29 days of storage), stabilisation of red colour (no change of CIE a* and hue angle after 23 days), maintenance of fresh meat odour (no variation of sensory score after 24 days) and significant (P<0.01) slowing of oxidative reactions (TBARS). PMID- 22061574 TI - Tenderness and collagen composition of beef semitendinosus roasts cooked by conventional convective cooking and modeled, multi-stage, convective cooking. AB - Beef semitendinosus roasts were cooked in a forced-air convection oven using conventional or modeled, multi-stage cooking. Conventional cooking was defined as cooking at 163 degrees C to a core endpoint of 65 degrees C. The model method was developed using a finite difference heat and mass transfer model optimized for a three-stage cooking process that included preheating, holding, and finishing. Model cooking resulted in lower (P<0.05) Warner-Bratlzer peak shear force values than conventional cooking (3.3 vs 4.7 kg). Collagen total unaltered fraction was lower (44 vs 55%, P=0.05) and enzyme labile fraction was higher (56 vs 45%, P<0.05) in the model-cooked samples than in conventionally cooked samples. The three-stage cooking process results in a more tender product without adversely affecting product yield. PMID- 22061575 TI - Evaluation of transglutaminase on the quality of low-salt chicken meat-balls. AB - The purpose of this study was to examine the effect of different concentrations of crude pig plasma transglutaminase (TGase) at 0, 0.05, 0.1, 0.2, 0.4 and 1.0% on the quality of low-salt chicken meat-balls. Yield, color, gel strength, microstructure and sensory evaluation were measured. The results showed that both the yield and gel strength of the meat-balls increased as TGase supplement increased (P<0.05) without any obvious effect on color. Scanning electron microscopy (SEM) indicated firmer and more regular gel structures with increasing TGase addition. Texture, juiciness and overall acceptability as judged by sensory evaluation were not statistically affected until the level of TGase reached 1.0% (P<0.05). PMID- 22061576 TI - Microbiological shelf life of bulk-packaged Musculus gluteus medius supplemented with dietary vitamin E. AB - Five Simmentaler type calves were fed diets supplemented with 500 mg vitamin E per day and five fed control diets. Rump steaks from each carcass were PVC overwrapped and bulk packaged in 100% CO, or 20% CO(2):80% O(2). Bulk packs were stored up to 42 days at 4 degrees C and steaks displayed up to 7 days at 4 degrees C. Bacterial counts of rump steaks from either packaging treatment were not significantly influenced during bulk storage or retail display by supplementation with dietary vitamin E. Both packaging treatments delayed bacterial growth during bulk storage. Aerobic plate counts of rump steaks stored in 100% CO(2) were lower than those of rump steaks stored in 20% CO(2): 80%: O(2). This study showed that rump steaks supplemented with dietary vitamin E can be bulk packaged in 20% CO(2): 80% O(2) or 100% CO(2) and stored for up to 42 days with shelf life of 4-7 days. PMID- 22061577 TI - Comparison of different magnesium sources on lamb muscle quality. AB - Wether lambs (n=20) were used to compare the effect of dietary magnesium oxide (MgO), unweathered Magnesium Mica(r) (UMM) and weathered Magnesium Mica(r) (WMM) on muscle quality. Lambs were fed a corn-based, control diet (Ctrl), or the Ctrl supplemented with either MgO, UMM, or WMM for 95 days before harvest. Following a 24-h chill, carcasses were fabricated, and L*, a* and b* values were determined on the triceps brachii (TB), longissimus thoracis (LT), semimembranosus (SM), and semitendinosus (ST) muscles. Supplemental magnesium had no (P > 0.10) effect on live and carcass weights, fat thickness, loin eye area, and USDA yield grade. Carcasses from lambs supplemented with MgO had higher (P < 0.10) flank streaking scores and USDA quality grades than those from lambs fed diets containing UMM. Although magnesium-supplementation had no (P > 0.10) effect on marbling scores, the LT from Ctrl-fed lambs had more (P < 0.05) intramuscular lipid than lambs fed diets containing UMM or WMM. Lambs supplemented with UMM had greater (P < 0.05) LT shear force values than lambs fed MgO or WMM. Magnesium-supplementation had no (P > 0.10) effect on muscle color; however, supplementing finishing diets with UMM may result in less palatable lamb. PMID- 22061578 TI - The effect of ionic strength, polyphosphates type, pH, cooking temperature and preblending on the functional properties of normal and pale, soft, exudative (PSE) pork. AB - Compared to processed meat product made from normal pork, products made from pale soft exudative (PSE) pork have higher cook loss (CL) and weaker texture. In this study interactions between a range of processing conditions (ionic strength, polyphosphate addition, polyphosphate chain length, pH, cooking temperature and time between preparation and cooking), and their effect on the texture [shear stress (SS), true shear strain (TSS)] and CL of gels made from normal and PSE pork were examined. Of the processing conditions studied, ionic strength, polyphosphate addition and polyphosphate chain length affected the functional properties of normal and PSE pork differently. Generally, the functional properties of normal pork were superior to PSE pork, with no combination of conditions making all the functional properties of PSE pork equal to those of normal pork under the same conditions. The combination of conditions that was most effective in reducing the difference between normal and PSE pork was high ionic strength in the presence of added polyphosphate. Under these conditions there was no significant difference in CL between normal and PSE pork, although the texture (SS and TSS) of the PSE pork samples was still inferior. PMID- 22061579 TI - Effects of fat level and maltodextrin on the functional properties of frankfurters formulated with 5, 12 and 30% fat. AB - The effects of fat level (5, 12 and 30%) and maltodextrin on emulsion stability, cook loss, colour, texture and sensory characteristics of frankfurters were investigated. Three fat levels (5, 12 and 30%) were formulated containing added maltodextrin. For each fat level a control was prepared without added maltodextrin giving a total of 6 treatments (3*2 factorial design). Reducing the fat from 30 to 5% increased cook loss and decreased emulsion stability. Panellists detected an increase in juiciness and a decrease in overall texture, overall acceptability when the fat level was reduced from 30 to 5%. Instron texture profile analysis showed a decrease in hardness, chewiness and gumminess and an increase in springiness with decreasing fat level. Maltodextrin addition caused a significant decrease in cook loss of the frankfurters but also decreased the emulsion stability. An interactive effect (P<0.05) occurred between fat level and maltodextrin resulting in no significant difference in hardness, gumminess and chewiness values when maltodextrin was present in the reduced-fat (5 and 12%) frankfurters. Saltiness, overall flavour intensity, overall texture and overall acceptability were unaltered (P>0.05) by maltodextrin. The results indicate that maltodextrin can be used as a suitable fat replacer since it offset some of the changes brought about by fat reduction, decreasing cook loss and maintaining a number of textural and sensory characteristics of the frankfurters. PMID- 22061580 TI - Effect of trisodium phosphate solutions washing on the sensory evaluation of poultry meat. AB - The effect of trisodium phosphate (TSP) solutions treatments on the sensory evaluation of poultry meat has been explored since TSP was recently approved by USDA for its usage in poultry processing to eliminate Salmonella contamination. In the present study, fresh chicken thighs were dipped in water (control sample) and in 8, 10 and 12% TSP solutions (treated samples) for 15 min. Raw samples' color, smell and overall acceptability and cooked thighs' color, smell, flavor, texture and overall acceptability were evaluated by consumer panelists. The evaluation of raw pieces after treatment or after 7 days storage at 2 degrees C revealed that, with the exception of 12% TSP solutions treatment, sensory quality was not adversely affected by TSP. The color, smell and overall acceptability hedonic scores for the boiled thigh meat were not different between the treated samples and the control ones. Only the color, flavor and overall acceptability of thighs dipped in 12% TSP were rated significantly lower than the control sample. These results suggested that TSP solutions have good potential as dips to sanitize chickens carcasses. PMID- 22061581 TI - Reduced nitrite levels and dietary alpha-tocopheryl acetate supplementation: effects on the colour and oxidative stability of cooked hams. AB - The objective of the present study was to determine the effects of dietary vitamin E supplementation and reduced nitrite levels on the colour stability of cooked hams. Large white * Landrace pigs (male n=6, female n=6) were each subdivided into two groups (n=3) and fed an alpha-tocopheryl acetate supplemented diet (1000 mg/kg feed) and a basal diet (10 mg/kg feed) for a period of 10 weeks. M. semitendinosus were removed from each pig, divided into light and dark pigmented fractions, vacuum packed and stored at 4 degrees C for 24 h. Muscles were cured with input nitrite levels of 25 and 100 mg/kg meat and were tumbled and massaged for 17 h. Samples were cooked, sliced and overwrapped in a high oxygen permeable film for a storage period of 10 days. Surface colour of hams was measured and expressed as Hunter 'a' values. Concentrations of alpha-tocopherol were significantly (P<0.001) greater in supplemented muscles compared to basal muscles for both male and female pigs. Hams manufactured from male and female supplemented pigs resulted in significantly (P<0.001) higher Hunter 'a' values than hams manufactured from male and female pigs receiving the basal diet. Muscles cured with 100 mg nitrite/kg meat formed products with significantly (P<0.001) higher 'a' values than those cured with the lower (25 mg/kg meat) nitrite level. Hams manufactured from supplemented muscles, treated with 25 mg nitrite/kg meat showed significantly (P<0.05) higher Hunter 'a' values than hams manufactured from basal muscles, treated with 100 mg nitrite/kg meat. Hams manufactured from female porcine muscles had significantly (P<0.001) higher 'a' values than hams from male muscles during the 10 days of simulated retail display. No such gender differences were observed for TBARS values. PMID- 22061582 TI - Effects of chemical hurdles on microbiological and oxidative stability of a cooked cured emulsion type meat product. AB - Two combinations of hurdles, 2.0% lactate+0.5% acetate or 2.0% lactate+0.25 % glucono-delta-lactone (GdL), were both found to prevent growth of Listeria monocytogenes inoculated onto sliced saveloys manufactured with 60 or 150 ppm nitrite. The saveloys were packed in modified atmosphere (80% N(2)/20% CO(2)) using a film with low oxygen transmission rate (0.45 cm(3)/m(2)/atm/24 h) and stored at 5 or 10 degrees C for up to 4 weeks. Changes in red colour (measured as Minolta a-values) and lipid oxidation [measured as thiobarbituric acid reactive substances (TBARS)] were low during storage at 5 degrees C and unaffected by the storage conditions (+/-light). However, 2.0% lactate+0.25% GdL improved oxidative stability and led to significantly lower TBARS and significantly higher a-values. Levels of nitrosamines were low with values near the detection level. Although observed differences were small, members of a trained sensory panel were able to distinguish saveloys containing chemical hurdles from saveloys without. Judges most often mentioned flavour as being the deviating descriptor. PMID- 22061583 TI - Evaluation of a probe for predicting beef tenderness. AB - A series of three experiments were conducted to evaluate the performance of the MIRINZ (Meat Industry Research Institute of New Zealand) tenderness probe. In the first experiment, assessments on raw samples from two different muscles (longissimus lumborum and semimembranosus) were obtained using the tension head. Results indicated D50 values (torque at 50 degrees of rotation) were the most highly related to both sensory (taste, olfactory, and feeling factors measured by a trained sensory panel) and consumer (hedonic ratings provided by untrained consumers) properties and were the values of choice, since all probe values were essentially measuring the same characteristics. In the second experiment, assessments were made using both the tension and shear heads on raw and cooked striploin (longissimus lumborum) steaks. Results confirmed probe values were essentially measuring the same characteristics, but indicated raw tension head, area 2 values (area before 50 degrees of rotation) were more highly related to both sensory and consumer properties than were D50 values. However, probe values from raw samples did not account for a sufficient amount of variation in either sensory or consumer properties to be useful predictors of these traits, and stepwise, linear regression did not improve the predictive value of raw probe values, since all probe values were interrelated. Probe values on cooked samples indicated the shear head and area 3 values (area under the entire trace) were the most related to both sensory and consumer properties and were the values of choice. Based upon the amount of variation accounted for in sensory and consumer traits, probe area 3 values using the shear head on cooked samples provided greater predictive value for both sensory and consumer traits than Warner Bratzler shear values obtained from steaks cooked either fresh or after being frozen and thawed. In experiment 3, correlations with individual, parametric character notes from the texture profiles of two different muscles provided no clear indication as to the textural properties being assessed by the probe. However, the MIRINZ probe appears to be a quick viable alternative to the Warner Bratzler shear for providing an objective measure of cooked meat tenderness. PMID- 22061584 TI - The measurement of pH in raw and frozen turkey Pectoralis superficialis muscle. AB - The objective of this study was to validate a rapid method for muscle pH assessment. Early pH is a good indicator of turkey breast meat quality. The stabilisation of pH can be obtained by homogenising fresh muscle in iodoacetate, but it is time consuming and not appropriate to the rate of poultry slaughter line. To reduce the time required for pH assessment, we compared different methods (homogenisation in iodoacetate of fresh (reference method), frozen and freeze-dried samples, direct measurement in tissue). Freezing the samples in liquid nitrogen before homogenisation in iodoacetate buffer could be substituted to the reference method for the measurement of pH at 3 and/or 20 min post mortem. For ultimate pH, however, the relationships were not good enough to substitute a new procedure to the reference method. PMID- 22061585 TI - Microbiological conditions of meats from large game animals and birds. AB - Large game animals and birds used for the commercial production of meat include deer of various species, wild boar and feral pigs, ostriches, emus and rheas, crocodiles and alligators, bison, and kangaroos. Meat from feral pigs and kangaroos is obtained from wild animals only, but much or most meat from the other game animals or birds is obtained from farmed animals. The microbiological conditions of meats from hunted animals can be compromised by poor placement of shots, the usual evisceration and sometimes further dressing of carcass in the field, and ageing of carcasses at ambient temperatures. However, the general microbiological conditions of carcasses from farmed game animals or birds slaughtered and dressed at suitable abattoirs can be comparable with or better than the microbiological conditions of carcasses from domestic animals or birds. The incidences of enteric pathogens on meat from wild or farmed game animals or birds can be less than those for meat from intensively reared domestic animals, but infection of some game meats with Trichinella or other foodborne parasites may occur. PMID- 22061586 TI - Development of DNA markers for discrimination between domestic and imported beef. AB - In the meat industry, correct breed information in food labeling is required to assure meat quality. Genetic markers provide corroborating evidence to identify breed. This paper describes the development of DNA markers to discriminate between Japanese and Australian beef. Two Bos indicus-specific markers and MC1R marker were used as possible candidate markers. Amplified fragment length polymorphism method was employed to develop additional candidate markers. The 1564 primer combinations provided three markers that were converted into single nucleotide polymorphisms markers for high-throughput genotyping. In these markers, the allele frequencies in cattle from both countries were investigated for discrimination ability using PCR-RFLP. The probability of identifying Australian beef was 0.933 and probability of misjudgment was 0.017 using six selected markers. These markers could be useful for discriminating between Japanese and Australian beef and would contribute to the prevention of falsified breed labeling of meat. PMID- 22061587 TI - Changes in the amounts of water-soluble umami-related substances in porcine longissimus and biceps femoris muscles during moist heat cooking. AB - Time course changes in amounts of glutamic acid, total free amino acid, inosine monophosphate (IMP), and 2%-trichloroacetic acid-soluble oligopeptides in whole, muscle only, and cooking juice during wet-heat cooking in pork longissimus and biceps femoris muscles were investigated because the movements of umami-relevant substances during cooking treatment had not previously been clarified in detail. The amounts of glutamic acid, total free amino acid, and IMP significantly (P<.05) decreased and increased in muscle and cooking juice during 180min of cooking, respectively. The whole amounts of glutamic acid and total free amino acid remained unchanged during cooking treatment. The whole amount of IMP, however, increased significantly at 10min of cooking (P<.05) and was maintained after the 10-min period. The extramuscular oligopeptides amount increased significantly in response to the cooking treatment (P<.05). The intramuscular amount of oligopeptides decreased at 30min of cooking but increased significantly (P<.05) after 60min. The whole meat oligopeptides amount increased significantly during a 180-min cooking treatment (P<.05). These results indicate that glutamate, total free amino acid, and IMP were released from the muscle during cooking, and that IMP levels increased in the initial phase of cooking. In addition, oligopeptides increased during wet-heat cooking of pork muscles. PMID- 22061588 TI - Effect of total replacement of pork backfat with walnut on the nutritional profile of frankfurters. AB - The nutritional profile of a frankfurter with walnut (25%) (WF) was compared with that of low fat (6%) (LF) and normal fat (16%) (NF) sausages. LF frankfurters did not improve the fatty acid profile as compared with NF (p>0.05), or the indices of atherogenicity (IA) (0.50) or thrombogenicity (IT) (1.12), indicating that the reduction of animal fat produced no cardioprotective effect. However, frankfurter with walnut had a healthy polyunsaturated fatty acid profile, a lower omega 6/omega-3 ratio and lower IA (0.10) and IT (0.15). In addition, WF could be a good source of manganese, iron, copper, potassium and magnesium, supplying 39%, 35%, 34%, 16% and 15% of the respective daily recommended intakes, respectively. Also, there were significant amounts of other bioactive components such as alpha ,gamma- and delta-tocopherol, total dietary fibre, polyphenols and tannins. The amino acid composition of WF indicated a healthier lysine/arginine ratio (0.83) than in LF (1.23) and NF (1.19). PMID- 22061589 TI - Phenotypic correlations among quality traits of fresh and dry-cured hams. AB - In this study, fresh and processing quality traits were collected on a total of 312 Country Hams. Phenotypic correlations between traits were estimated and numerous values were significantly different (P<0.05) from zero. Yield was significantly correlated with several fresh pork quality traits measured on the fresh hams, including subjective color (0.34) and lipid percentage (0.32). Some meat color traits were significantly correlated, including associations between the color scores taken on the fresh and cured hams. Correlations between fresh pork quality traits were also determined, with results showing significant correlations between ultimate pH and other pork quality traits. The results indicate that yield can be maximized if hams with good fresh pork quality parameters are used for curing. The correlations estimates are helpful for understanding of the biological mechanisms behind the production of dry-cured hams and can potentially be used to improve the efficiency of the dry-cured ham production chain. PMID- 22061590 TI - Relationship between water mobility and distribution and sensory attributes in pork slaughtered at an age between 90 and 180 days. AB - Water mobility and distribution were measured in M. longissimus dorsi from 41 pigs slaughtered at an age of 90, 140, 161 or 182 days using low-field proton NMR relaxometry, and in order to investigate the impact on sensory attributes, a sensory evaluation of the pork was performed in parallel. The sensory evaluation demonstrated a significant effect of slaughter age on juiciness of the meat, and a final juiciness score of 8.4, 7.7, 7.2 and 7.8 was obtained for meat from 90, 140, 161 and 182-day old pigs, respectively. The NMR measurements revealed that the higher juiciness in meat slaughtered at an age of 90 days could be ascribed to a longer relaxation time of the extramyofibrillar water, corresponding to more mobile water, in the fresh meat of 90-day old pigs compared with the older pigs. In the cooked meat the higher juiciness of meat from 90-day old animals could be ascribed to a more homogenous distribution of the myofibrillar water compared with meat from older pigs. In contrast, the NMR measurements showed no effects that could explain the higher juiciness in meat from pigs slaughtered at an age of 182 days compared with meat from pigs slaughtered at an age of 140 or 161 days. Possibly the increase in juiciness when the age at slaughter is increased from 161 to 182 days should be ascribed to an increase in intramuscular fat content, which was not evident in the NMR measurements. PMID- 22061591 TI - Feeding feedlot steers fish oil alters the fatty acid composition of adipose and muscle tissue. AB - Sixteen steers (441+/-31.7kg initial body weight) consumed two high concentrate diets with either 0 or 3% fish oil to determine the impact of fish oil, an omega 3 fatty acid source, on the fatty acid composition of beef carcasses. Collected tissue samples included the Longissimus thoracis from the 6th to 7th rib section, ground 10th to 12th rib, liver, subcutaneous adipose tissue adjacent to the 12th rib, intramuscular adipose tissue in the 6th to 7th rib sections, perirenal adipose tissue, and brisket adipose tissue. Including fish oil in the diet increased most of the saturated fatty acids (P<0.01) and proportions of polyunsaturated fatty acids (P<0.06), and decreased (P<0.01) proportions of monounsaturated fatty acids. Dietary fish oil increased (P<0.01) levels of omega 3 fatty acids in sampled tissues, resulting in lower (P<0.01) omega-6:omega-3 ratios. The weight percentages of C20:5 and C22:6 in tissue may provide the recommended daily allowance for humans. Fish oil may have a role in beef niche marketing if there are no deleterious effects on consumer satisfaction. PMID- 22061592 TI - Characterization and technological properties of Staphylococcus xylosus strains isolated from a Tunisian traditional salted meat. AB - The technological properties of strains of Staphylococcus xylosus were studied to select the most suitable for use as starter cultures for the production of dried fermented meat products. Strains of S. xylosus were isolated from traditional salted Tunisian meat and were identified by biochemical and molecular methods. Thirty strains of S. xylosus were studied to evaluate their catalase, nitrate reductase, lipolytic, proteolytic and antibacterial activities as well as growth ability at different temperatures, pH's and NaCl concentrations. All strains of S. xylosus had catalase activity and were able to reduce nitrates to nitrites. The nitrate reductase activity increased when the strains were kept under anaerobic conditions. Proteolytic activity on milk and on gelatin agar was demonstrated for 100% and 83.3% of the S. xylosus isolates, respectively. However extracellular proteolytic activity as assessed by the azocasein method was poor in all the strains. Lipolytic activity as assessed by the agar method showed that 76.6% of strains of S. xylosus could hydrolyze Tween 20 against 33.3% that could hydrolyze tributyrin. Tween 80 was hydrolyzed by only 10% of strains. Strains of S. xylosus hydrolyzed pork fat better than beef and lamb fat. The majority of strains had antibacterial activity against Salmonella arizonae, Staphylococcus aureus, Pseudomonas aeuroginosa, Escherichia coli and Enterococcus faecalis. PMID- 22061593 TI - Evaluating an objective method to measure fresh pork loin firmness. AB - The purpose of this study was to develop an objective method for measuring fresh pork loin firmness. A total of 42 fresh boneless pork loins were collected from a range of subjective firmness scores based on the whole boneless loin to create a population suitable for creating a prediction equation. Loins were subjectively scored by panelists prior to objectively being measured with a Texture Analyzer. An R(2) value of 0.54 was achieved for the prediction equation that was generated. A second trial was performed to test the equation resulting in an R(2) value of 0.30 concerning subjective and objective values. The results from these studies indicate that it is possible to create a standardized protocol in order to determine objective firmness that would be useful for future studies and for the development of hand held or online firmness measuring devices. PMID- 22061594 TI - Development of breast muscle and meat quality in Arbor Acres broilers, Jingxing 100 crossbred chickens and Beijing fatty chickens. AB - The objective of this experiment was to examine development of breast muscle and myofiber of M. pectoralis superficialis in three chicken breeds. Commercial broiler chickens (Arbor Acres broilers, AA), crossbred chickens (Jingxing 100 crossbred chickens, JXC) and Chinese native chickens (Beijing fatty chickens, BJF) were grown up to 98d to estimate myofiber density, and size (area, and diameter of myofibers) in P. superficialis. At 42, 56, 70, 84, and 98d of age, Pectoralis muscle was used to evaluate breast muscle weight, breast yield, and tenderness (shear force value). Results indicate that commercial broilers have higher breast weight, and higher shear force value than crossbred chickens and Chinese native chickens, that may be due to an increased myofiber diameter and area in Pectoralis muscle. It is suggested that histological properties of myofibers play an important role in increasing the shear force value of meat. PMID- 22061595 TI - Effect of biotin supplementation on meat quality of F1 Wagyu/Black Angus feedlot steers of known genotype. AB - Biotin (D-biotin) was supplemented to F1 Wagyu/Black Angus steers fed a wheat based ration to evaluate the effect on meat quality. One hundred and eight steers of known Wagyu sire lines were assigned to three biotin treatments (0, 10 and 20mg/head/day) with each treatment replicated four times using an unfasted liveweight of 410.5kg (+/-24.42 SD). Biotin supplementation had no effect (P>0.05) on beef marbling standard at either the 5/6th or 10/11th rib quartering site, 10/11th rib intra-muscular fat percentage, intra-muscular fat fatty acid composition or adipose melting points. Wagyu genotype had an effect (P<0.05) on beef marbling standard and intra-muscular fat percentage at the 10/11th rib, inter-muscular and intra-muscular melting point and fatty acid composition of intra-muscular fat. A significant (P<0.001) but poor correlation existed between beef marbling standard and intra-muscular fat percentage (R(2)=0.198). Total conjugated linoleic acid had a highly significantly (P<0.0001) positive correlation to intra-muscular fat percentage (R(2)=0.446). PMID- 22061596 TI - Kinetic migration studies from packaging films into meat products. AB - One of the main concerns regarding safety of food packaging is the possible migration of chemical substances (monomers and other starting substances, additives, residues) from food contact materials into foods. To evaluate the effect of the fat content and of the temperature of storage on the migration from plastics packaging films into meat products as an important class of foodstuffs, the kinetic mass transport of a model migrant (diphenylbutadiene) from low density polyethylene (LDPE) film in contact with different meat products was investigated. From the data, the diffusion coefficients were calculated for the applied test conditions, by use of a mathematical model. The results showed that migration increased with fat content and storage temperature. Analysis of migration data corresponding to minced pork meat containing different amounts of fat, stored for 10 days at 25 degrees C, revealed an excellent relationship between migration level and fat content. This behaviour was also found for other types of meat products (chicken and pork neck). A simplifying mathematical model was applied to derive effective diffusion coefficients in the polymer which, however, do take kinetic effects in the meat also into account. In the case of pork meat contact, the effective diffusion coefficients derived from mathematical modelling were ten times higher for storage at 25 degrees C (1.88*10(-9)cm(2)s( 1)) than for storage at 5 degrees C (1.2*10(-10)cm(2)s(-1)). PMID- 22061597 TI - Extensive feeding versus oleic acid and tocopherol enriched mixed diets for the production of Iberian dry-cured hams: Effect on chemical composition, oxidative status and sensory traits. AB - The present study aimed to analyse the chemical composition and oxidative status of Iberian dry-cured hams from pigs fed different finishing diets: extensive feeding on acorns and pasture in a "Montanera" traditional system (MON), fed in confinement with a mixed diet containing high-oleic sunflower oil (115g/kg of diet) and supplemented with 250mg/kg alpha-tocopherol (HOVE), and fed in confinement control mixed diet (CON) without added tocopherol and oleic acid fat. Muscles from MON dry-cured hams contained significantly (p<0.05) higher amounts of intramuscular fat (IMF) than those from HOVE and CON hams. The feeding background affected the tocopherol levels in dry-cured hams as those from MON and HOVE pigs had significantly higher levels of alpha-tocopherol than those from CON pigs whereas the extensive feeding provided muscles from MON pigs with significantly higher levels of gamma-tocopherol than the experimental diets did to CON and HOVE pigs. The HOVE diet significantly increased the levels of oleic acid in Iberian dry-cured hams with these levels being similar to the oleic acid levels found in MON hams and significantly higher than those in CON hams. Compared to dry-cured hams from CON pigs, those from MON and HOVE pigs exhibited a higher oxidative stability as a likely result of a most favourable fatty acid composition and the presence of higher tocopherol levels. The principal component analysis (PCA) successfully discriminated between dry-cured hams from pigs fed different finishing diets. PMID- 22061598 TI - Titin-cap (TCAP) polymorphisms associated with marbling score of beef. AB - Marbling score (MS) is the major qualitative trait that affects carcass quality in beef cattle. In this study, we examined the association between genetic polymorphisms of the titin-cap gene (TCAP) and carcass traits in Korean native cattle (also known as Hanwoo). By direct DNA sequencing in 24 unrelated Korean cattle, we identified five sequence variants in 1.2kb of TCAP. Among them, four common polymorphic sites were selected for genotyping in the beef cattle (n=437). Pair-wise linkage analysis with four polymorphisms showed strong linkage disequilibrium (LD), and three major haplotypes (freq.>0.1) were constructed. Statistical analysis revealed that polymorphisms in intron1 (g.346G>A) and exon2 (g.592-597CTGCAG[Leu-Gln]insdel) showed significant association with marbling score (P(cor.)=0.003 and 0.02, respectively). One haplotype, ht2[C-G-G-del], also showed significant association with MS (P(cor.)=0.0004). Our findings suggest that polymorphisms in TCAP might be among the important genetic factors involved in carcass quality in beef cattle. PMID- 22061599 TI - Effects of dietary supplementation of vitamins D(3) and E on quality characteristics of pigs and longissimus muscle antioxidative capacity. AB - The effects of addition of vitamin D(3) and vitamin E to pig diets on blood plasma calcium concentration, meat quality (longissimus muscle) and antioxidative capacity were investigated. Two treatments consisted of supplementation with vitamin D(3) (500,000IU/d) for 5 days separately (group D) and a combination of vitamin E (500mg alpha-tocopheryl acetate/kg diet) for 30 days and vitamin D(3) (500,000IU/d) for 5 days (group D+E) to growing-finishing pigs before slaughter. Pigs fed with vitamin D(3) had higher (P<0.01) plasma calcium concentration compared with control pigs. Dietary supplementation of vitamin E significantly (P<0.05) increased the concentration of alpha-tocopherol in meat (longissimus muscle). Vitamin D(3) supplementation resulted in higher (P=0.07) a(*) values of loin chops at 5 days of storage. Vitamin D(3) and vitamin E supplementation did not affect other meat quality characteristics or tenderness (quantified by Warner Bratzler shear force). Antioxidative capacity (measured as MDA production after incubation of longissimus muscle homogenates with Fe(2+)/ascorbate) was improved by vitamin E and partly by vitamin D(3) supplementation. PMID- 22061600 TI - Changes in the content of biologically active polyamines during storage and cooking of pig liver. AB - Dietary polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) participate in numerous human physiological processes, including tumour growth. Eight experiments with pig liver were carried out. In two, livers were stored at 18 degrees C for 168 days, in four, livers were stored aerobically (AE), vacuum packaged (VP) and packaged in a modified atmosphere (MO; 70% N(2) and 30% CO(2), v/v) at +2 degrees C for 9, 21 and 21 days, respectively, and in two, the effects of four cooking treatments were tested. Polyamines were determined as dansyl derivatives using an HPLC method. Distribution of both SPD and SPM in the four main liver lobes was homogenous. The initial SPD and SPM contents in 14 livers 24h after slaughter were 23.3+/-6.7 and 94.5+/-19.6mgkg(-1), respectively. The putrescine content was below the limit of detection. The content of SPD and SPM decreased during frozen-storage to about 70% of the initial values. On day-9 of storage, mean SPD and SPM contents decreased to about 85% of the initial values in livers stored in MO and to about 75-80% in AE and VP at 2 degrees C. The decrease continued more extensively in VP than in MO. PUT was detected from day 15 of VP and MO storage. There was a significant decrease in SPD and SPM, to about 70-60% of the initial content during cooking. PMID- 22061601 TI - Significance of fat supplemented diets on pork quality - Connections between specific fatty acids and sensory attributes of pork. AB - The influence of two diets with different fatty acid compositions has been studied with regard to overall pork quality and significance of specific fatty acids on sensory attributes in fried chops and oven roasts. Twenty castrates and 20 females were in a balanced experimental set-up fed with a standard diet supplemented with alpha-tocopherol (200mg/kg feed) where the fat source was either 3% of palm oil or 3% rapeseed oil. After slaughter, despite differences in lipid composition and sensory attributes, no significant difference in overall meat quality parameters and flavour precursors was found. Comparison of the two diets showed that supplementation with rapeseed oil resulted in a significantly higher content of C18:3n-3 (polar lipid (PL), neutral lipid (NL)), C18:2n-6c (NL) and C20:2 (NL) in LD and C18:1n-9c, C18:2n-6c, C18:3n-3, C20:3n-3, C22:5n-3 in backfat, while supplementation with palm oil resulted in a higher content of C16:0 (NL), C16:1 (PL), C18:1n-9t (NL) in LD and C16:0, C17:0, C18:0, C16:1, C20:4n-6 in backfat. A positive and significant correlation between the contents of C18:2n-6c, C20:3n-6 in the PL fraction and the sensory attributes fried meat odour and sweet odour were found in fried pork chops from female pigs. Likewise, positive correlations were seen between the content of C18:1n-9c in the PL fraction and sensory attributes such as sourish odour, piggy odour and piggy flavour in whole oven roasts. These data substantiate the view that specific fatty acids in the PL fraction influences flavour attributes in pork. PMID- 22061602 TI - Biogenic amine content during the manufacture of dry-cured lacon, a Spanish traditional meat product: Effect of some additives. AB - The content of nine biogenic amines (agmatine, tryptamine, 2-phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine and spermine) was determined throughout the manufacture of dry-cured lacon, a traditional dry salted and ripened meat product made in the north-west of Spain from the fore leg of the pig following a similar process to that of dry-cured ham. The effect of the use of additives (glucose, sodium nitrite, sodium nitrate, sodium ascorbate and sodium citrate) on the biogenic amine content during manufacture was also studied. Tryptamine and spermine were the main biogenic amines in fresh meat, while tryptamine and cadaverine were the most abundant at the end of the manufacturing process. During ripening the total amine content increased significantly (P<0.05) in the batches made both without and with additives. The use of additives significantly (P<0.05) increased the total amine content and the content of tryptamine, tyramine and histamine. The total biogenic amine content at the end of the manufacturing process was low as expected for a product in which there is little active microbial metabolism during manufacture. PMID- 22061603 TI - Forty-eighth International Congress of Meat Science and Technology-Rome 25-30 August 2002 Meat, nutrition, development. PMID- 22061604 TI - Use of irradiation for microbial decontamination of meat: situation and perspectives. PMID- 22061605 TI - Current and future technologies for the decontamination of carcasses and fresh meat. AB - The objective of this review is to describe current methods and technologies used to decontaminate food animal carcasses in the United States and describe new technologies and methods that are under development. Bacterial reduction during the conversion of muscle to meat has always been an important challenge for the meat processing industry due to the impact on product safety and quality. More intense microbiological testing and improved microbiological methods have led to a greater awareness by industry and government about the levels of pathogenic bacteria on meat carcasses and in meat products. This increased awareness has spurred research and development on new technologies implemented sequentially in the process, aimed at reducing and eliminating bacteria on carcasses and meat products. PMID- 22061606 TI - Managing meat tenderness. AB - This paper discusses the management of meat tenderness using a carcass grading scheme which utilizes the concept of total quality management of those factors which impact on beef palatability. The scheme called Meat Standards Australia (MSA) has identified the Critical Control Points (CCPs) from the production, pre slaughter, processing and value adding sectors of the beef supply chain and quantified their relative importance using large-scale consumer testing. These CCPs have been used to manage beef palatability in two ways. Firstly, CCPs from the pre-slaughter and processing sectors have been used as mandatory criteria for carcasses to be graded. Secondly, other CCPs from the production and processing sectors have been incorporated into a model to predict palatability for individual muscles. The evidence for the importance of CCPs from the production (breed, growth path and HGP implants), pre-slaughter and processing (pH/temperature window, alternative carcass suspension, marbling and ageing) sectors are reviewed and the accuracy of the model to predict palatability for specific muscle*cooking techniques is presented. PMID- 22061607 TI - Lipids in muscles and adipose tissues, changes during processing and sensory properties of meat products. AB - Dry-cured meat products represent a large part of the meat products on the European market. The technologies develop for these products lead to the production of a large scale of meat products with typical sensory traits. Numerous studies have been devoted to optimise the quality traits of these products which are considered as traditional products by the consumer and provide a high added value to the producer. Among the components of the raw material, lipids play a key role in the final quality of these products. Many sensory traits of dry-cured meat products depend on lipid traits of muscle and adipose tissues of fresh meat and on their degradation through a complex set of lipolytic and oxidative reactions during processing. Lipid traits of both muscle and adipose tissues of fresh meat are strongly related to pig rearing conditions, mainly genotype and feeding strategy. During processing, lipids undergo intense lipid hydrolysis controlled by both lipases and phospholipases, which remain active all along the process. Lipids are also subjected to oxidation, which generates numerous volatile compounds. These volatiles contribute to some typical aroma notes of dry-cured meat products such as rancid, aged ham and dry-cured odours. This paper reviews the recent knowledge on the influence of lipid traits of fresh meat, lipid hydrolysis and oxidation on the development of sensory traits of dry-cured meat products. PMID- 22061608 TI - Validation of manufacturing process to control pathogenic bacteria in typical dry fermented products. AB - Safety is the prime consideration and food manufacturers must ensure that products pose a minimum hazard to the consumer. The required safety must be achieved by preventing growth of pathogens during production and by reducing the remaining contamination to the lowest possible level. Dry and semi-dry fermented sausages are generally regarded as one of the most shelf-stable and safest meat products; they have rarely been implicated in food poisoning but sausage makers must ensure that their products do not harbour any pathogen bacteria. To ensure that processing is sufficient to eliminate any biological hazard present in the product, procedures must be validated to demonstrate that they are able to achieve a specified reduction in terms of pathogenic bacteria. PMID- 22061609 TI - Muscle traits for long matured dried meats. AB - The distinctive flavour of aged pork products is a complex mix of taste, smell and even touch. To meet increasing consumer's preference for ethnic foods or foods addressing linkage with specified geographic origin or complying with traditional manufacturing and breeding guidelines, efforts should be made to encourage selection of processing techniques and raw materials targeting desired end product qualities. Thanks to research carried out with sensory analysis and chemical and physical characterisation of raw and matured pork, as well as breeding and genetics, improved knowledge is now available relating dried meat properties to raw matter or manufacturing. The achievement of the distinctive taste and texture properties of aged products through genetics (animal selection for the enhancement or the removal of some muscle traits), breeding (effect of diet and slaughtering age on pork properties) with reference to current findings about this type of products is discussed. PMID- 22061610 TI - Meat tenderness and muscle growth: is there any relationship? AB - Our objectives for this manuscript are to review the mechanisms of muscle growth, the biological basis of meat tenderness, and the relationship between these two processes. Muscle growth is determined by hyperplasia and hypertrophy. Muscle cell size is determined by the balance between the amount of muscle protein synthesized and the amount of muscle protein degraded. Current evidence suggests that the calpain proteolytic system is a major regulator of muscle protein degradation. Sarcomere length, connective tissue content, and proteolysis of myofibrils and associated proteins account for most, if not all, of the explainable variation in tenderness of meat after postmortem storage. The relative contribution of each of the above components is muscle dependent. The calpain proteolytic system is a key regulator of postmortem proteolysis. While changes in muscle protein degradation affect meat tenderization/tenderness, changes in muscle protein synthesis are not expected to affect meat tenderization/tenderness. PMID- 22061611 TI - Welfare of animal production in intensive and organic systems with special reference to Danish organic pig production. AB - Although organic meat production is only a small proportion of the total meat production in the EU, it is increasing in size to take the demands of certain market segments into account. Organic production standards vary according to organisation within countries but all must as a minimum fulfil EU legislative requirements. There is a greater potential for optimal welfare in organic systems compared to intensive systems, as the management of farm animals must take into account their physiological, social and behavioural needs. However, demands on management are greater in organic systems, particularly if these are free range, and concern has been expressed regarding animal health. Vaccinations, antibiotics and antihelmintics may only be used in a limited way in organic production and the use of natural and homeopathic products, whose efficacy has not been scientifically documented, must take precedence over veterinary medical products. Legislative requirements regarding the pre-slaughter handling of organic slaughter animals are essentially the same as for all other animals. In Denmark, ethical audits for documenting pig welfare during collection at the farm, during transport and at the abattoir have been proposed and tested on the initiative of the Pig Committee under the Association of Organic Meat Producers in Denmark. It is the hope of the Committee that these audits will be used within the EU to ensure optimal welfare for organic pigs in the pre-slaughter period. PMID- 22061612 TI - New mild technologies in meat processing: high pressure as a model technology. AB - As a consequence of market globalization, the production and manufacture of meat products is at a stage of innovative dynamics. Consumers demand high quality and convenient meat products, with natural flavour and taste, and very much appreciate the fresh appearance of minimally processed food. To harmonize or to blend all these demands without compromising safety, it is necessary to implement new preservation technologies in the meat industry and in the food industry in general. High hydrostatic pressure (HHP) represents an attractive non-thermal process for meat products to avoid post-processing contamination. When combined with antimicrobials, like bacteriocins, the death rate may be increased because of sublethal injuries to living cells. HPP is a powerful tool to control risks associated with Salmonella spp. and Listeria monocytogenes in raw or marinated meats. The HPP treatment could extend the shelf life of the marinated beef loin by controlling the growth of both spoilage and pathogenic bacteria. As a general conclusion it can be stated that from both a physico-chemical and microbiological point of view, cooked pork ham, dry cured pork ham and marinated beef loin, vacuum-packed and high pressure treated at 600 MPa for 10 min at 30 degrees C, are substantially equivalent to the same untreated products. PMID- 22061613 TI - Antimicrobial food packaging in meat industry. AB - Antimicrobial packaging, an active packaging concept, can be considered an extremely challenging technology that could have a significant impact on shelf life extension and food safety of meat and meat products. Use of antimicrobial substances can control the microbial population and target specific microorganisms to provide higher safety and quality products. Many classes of antimicrobial compounds have been evaluated in film structures, both synthetic polymers and edible films: organic acids and their salts, enzymes, bacteriocins, and miscellaneous compounds such as triclosan, silver zeolites, and fungicides. The characteristics of some antimicrobial packaging systems are reviewed in this article. The regulatory status of antimicrobial packaging in EU is also examined. PMID- 22061614 TI - Bacteriological safety issues in red meat and ready-to-eat meat products, as well as control measures. AB - The importance of Eschericha coli O157, Listeria monocytogenes and Salmonella typhimurium DT104 as meat-borne pathogens is well established. Pathogenic bacteria such as Aeromonas spp., Arcobacter spp., psychrotrophic Bacillus cereus, Campylobacter spp., Clostridium botulinum and non-invasive Listeria monocytogenes can be regarded as rookies, but not yet firmly associated with today's production of red meat and meat products. The development of PCR and other DNA-based techniques will shed new light on so called emerging pathogens. Important safety issues in meat production, such as insufficient cleaning and disinfection (including the stable/lairage, processing environment), carcass decontamination and chilling, and cross contamination are discussed. Furthermore, probability modelling of survival and growth is identified as an important way to achieve a better understanding of how to deal with the complexity of further processing, including heat treatment and storage. PMID- 22061615 TI - Single nucleotide polymorphism in the promoter region of the CD209 gene is associated with human predisposition to severe forms of tick-borne encephalitis. AB - Tick-borne encephalitis virus (TBEV) is a neurotropic, positive-sense RNA virus of the genus Flavivirus (family Flaviviridae) which can cause a variety of clinical manifestations in humans. Previously the severity and outcome of dengue fever and hepatitis C (diseases caused by viruses from the family Flaviviridae) were associated with the rs4804803 single nucleotide polymorphism (SNP) located in the promoter region of the human CD209 gene. This gene encodes dendritic cell specific ICAM3-grabbing nonintegrin (DC-SIGN), a C-type lectin pathogen recognition receptor expressed on the surface of dendritic cells and some types of macrophages. In the current study, a possible association between two SNPs in the promoter region of the CD209 gene (rs4804803 and rs2287886) and predisposition to severe forms of TBEV-induced disease was investigated. The genotypic, allelic and haplotypic frequencies of these SNPs were analyzed in 136 non-immunized Russian patients with different clinical manifestations of tick borne encephalitis (TBE) and in a control group. An increase in the frequency of the rs2287886 SNP AA homozygotes and the A allele was detected among patients with severe central nervous system disease compared with the group of patients with meningitis (P=0.003 and 0.019), or a combined group of patients with mild forms (fever and meningitis) (P=0.003 and 0.026), or the control group (P=0.007 and 0.035). Thus, our results suggest that the CD209 gene promoter region rs2287886 SNP is associated with predisposition to severe forms of TBE in the Russian population. PMID- 22061616 TI - Precore/core promoter mutations and hepatitis B virus genotype in hepatitis B and C dually infected patients treated with interferon-based therapy. AB - We studied the prevalence and distribution of precore/basal core promoter (BCP) mutations and hepatitis B virus (HBV) genotypes in HBV/hepatitis C virus (HCV) dually-infected patients, and evaluated their impact on long-term HBV response of interferon (IFN)-based therapy. The HBV genotypes and sequences of the precore/BCP regions were determined in 180 HBV/HCV dually-infected patients and were compared with 90 age, sex and hepatitis B e antigen-matched chronic hepatitis B controls. Serum HBV DNA and hepatitis B surface antigen (HBsAg) were assessed every 3-6 months after therapy with IFN or pegylated-IFN plus ribavirin in 135 dually-infected patients with active hepatitis C. Dually-infected patients had a higher prevalence of genotype C HBV (P=0.022) and a lower frequency of G1896A mutation (P=0.004) as compared with controls. Among dually-infected patients, genotype C was associated with a higher frequency of A1762T/G1764A mutation (P<0.001), but with lower HBV DNA (P<0.001) and a lower frequency of A1752T/G (P=0.008), C1799G (P<0.001) and G1896A mutation (P<0.001) than genotype B. Based on Cox proportional hazards model, young age (hazard ratio (HR)=0.952, P=0.001), sustained virological response to HCV (HR=4.638, P=0.044), C1766T mutation (HR=5.216, P=0.003) and A1846T mutation (HR=2.332, P=0.031) correlated with HBV DNA reactivation (?2000IU/ml) after therapy. Age (HR=1.068, P=0.020), G1896A mutation (HR=0.140, P=0.01) and A1846T mutation (HR=0.086, P=0.018) were associated with HBsAg seroclearance independently. In conclusion, specific mutations in the precore/BCP regions could be useful in predicting long-term HBV response in HBV/HCV dually-infected patients treated with IFN-based therapy. PMID- 22061617 TI - Genotypic characterization of herpes simplex virus DNA polymerase UL42 processivity factor. AB - The herpes simplex virus (HSV) DNA polymerase is composed of the UL30 catalytic subunit and the UL42 processivity factor. The UL42 subunit increases the processivity of the polymerase along the DNA template during replication. The molecular mechanisms of HSV resistance to drugs interfering with viral DNA synthesis reported so far mainly rely on modifications of the viral thymidine kinase and DNA polymerase. We aimed to extensively describe the genetic variations of HSV UL42 processivity factor and to evaluate its potential involvement in resistance to antivirals. The full-length UL42 gene sequence of HSV was investigated among two laboratory strains (KOS and gHSV-2), 94 drug sensitive clinical isolates and 25 phenotypically ACV-resistant clinical isolates. This work provided extensive data about natural variability of UL42 processivity factor among both HSV-1 and HSV-2 strains and showed that this viral protein is highly conserved among HSV strains, with a weaker variability for HSV 2. The analysis of 25 HSV clinical isolates exhibiting ACV-resistance documented most of the previously reported mutations related to UL42 natural polymorphism in addition to some unpreviously described polymorphisms. Surprisingly, a single base deletion in UL42 gene sequence leading to a frameshift in the C-terminal region was identified among 3 HSV clinical isolates. From this preliminary study, UL42 processivity factor did not seem to be likely involved in HSV resistance to antivirals. PMID- 22061618 TI - Rapid conversion of spirostans into furostan skeletons at room temperature. AB - We report a facile protocol to obtain 22-substituted furostans and pseudosapogenins in high yields from (25R)- and (25S)-sapogenins. This method involves the treatment of the sapogenin with acetic-trifluoroacetic mixed anhydride and BF(3).OEt(2) at room temperature, followed by the addition of a nucleophile (H(2)O, MeOH or KSeCN). In the case of 22-hydroxyfurostans, they can be transformed to pseudosapogenins by treatment with p-toluensulfonic acid. PMID- 22061620 TI - Impact of endocrine-disrupting compounds (EDCs) on female reproductive health. AB - Evidence is accumulating that environmental chemicals (ECs) including endocrine disrupting compounds (EDCs) can alter female reproductive development, fertility and onset of menopause. While not as clearly defined as in the male, this set of abnormalities may constitute an Ovarian Dysgenesis Syndrome with at least some origins of the syndrome arising during foetal development. ECs/EDCs have been shown to affect trophoblast and placental function, the female hypothalamo pituitary-gonadal axis, onset of puberty and adult ovarian function. The effects of ECs/EDCs are complex, not least because it is emerging that low-level, 'real life' mixtures of ECs/EDCs may carry significant biological potency. In addition, there is evidence that ECs/EDCs can alter the epigenome in a sexually dimorphic manner, which may lead to changes in the germ line and perhaps even to transgenerational effects. This review summarises the evidence for EC, including EDC, involvement in female reproductive dysfunction, it highlights potential mechanisms of EC action in the female and emphasises the need for further research into EC effects on female development and reproductive function. PMID- 22061619 TI - Regulation of TRPM8 channel activity. AB - Transient Receptor Potential Melastatin 8 (TRPM8) is a Ca(2+) permeable non selective cation channel directly activated by cold temperatures and chemical agonists such as menthol. It is a well established sensor of environmental cold temperatures, found in peripheral sensory neurons, where its activation evokes depolarization and action potentials. The activity of TRPM8 is regulated by a number of cellular signaling pathways, most notably by phosphoinositides and the activation of phospholipase C. This review will summarize current knowledge on the physiological and pathophysiological roles of TRPM8 and its regulation by various intracellular messenger molecules and signaling pathways. PMID- 22061621 TI - Discovery of a novel enzyme mediating glucocorticoid catabolism in fish: 20beta hydroxysteroid dehydrogenase type 2. AB - Hydroxysteroid dehydrogenases (HSDs) are involved in metabolism and pre-receptor regulation of steroid hormones. While 17beta-HSDs and 11beta-HSDs are extensively studied in mammals, only few orthologs are characterized in fish. We discovered a novel zebrafish HSD candidate closely related to 17beta-HSD types 3 and 12, which has orthologs in other species. The enzyme catalyzes the conversion of cortisone to 20beta-hydroxycortisone identified by LC-MS/MS. We named the new enzyme 20beta HSD type 2. All 20beta-HSD type 2 orthologs localize in the endoplasmic reticulum. Zebrafish 20beta-HSD type 2 is expressed during embryonic development showing the same expression pattern as 11beta-HSD type 2 known to oxidize cortisol to cortisone. In adult tissues 20beta-HSD type 2 shows a ubiquitous expression pattern with some minor sex-specific differences. In contrast to other enzymes metabolizing C21-steroids and being mostly involved in reproduction we propose that novel type 2 20beta-HSDs in teleost fish are important enzymes in cortisol catabolism. PMID- 22061622 TI - Does the aromatic L-amino acid decarboxylase contribute to thyronamine biosynthesis? AB - Thyronamines (TAM), recently described endogenous signaling molecules, exert metabolic and pharmacological actions partly opposing those of the thyromimetic hormone T(3). TAM biosynthesis from thyroid hormone (TH) precursors requires decarboxylation of the L-alanine side chain and several deiodination steps to convert e.g. L-thyroxine (T(4)) into the most potent 3-T(1)AM. Aromatic L-amino acid decarboxylase (AADC) was proposed to mediate TAM biosynthesis via decarboxylation of TH. This hypothesis was tested by incubating recombinant human AADC, which actively catalyzes dopamine production from DOPA, with several TH. Under all reaction conditions tested, AADC failed to catalyze TH decarboxylation, thus challenging the initial hypothesis. These in vitro observations are supported by detection of 3-T(1)AM in plasma of patients with AADC-deficiency at levels (46 +/- 18 nM, n=4) similar to those of healthy controls. Therefore, we propose that the enzymatic decarboxylation needed to form TAM from TH is catalyzed by another unique, perhaps TH-specific, decarboxylase. PMID- 22061623 TI - Gene-environment interactions: the potential role of contaminants in somatic growth and the development of the reproductive system of the American alligator. AB - Developing organisms interpret and integrate environmental signals to produce adaptive phenotypes that are prospectively suited for probable demands in later life. This plasticity can be disrupted when embryos are impacted by exogenous contaminants, such as environmental pollutants, producing potentially deleterious and long-lasting mismatches between phenotype and the future environment. We investigated the ability for in ovo environmental contaminant exposure to alter the growth trajectory and ovarian function of alligators at five months after hatching. Alligators collected as eggs from polluted Lake Apopka, FL, hatched with smaller body masses but grew faster during the first five months after hatching, as compared to reference-site alligators. Further, ovaries from Lake Apopka alligators displayed lower basal expression levels of inhibin beta A mRNA as well as decreased responsiveness of aromatase and follistatin mRNA expression levels to treatment with follicle stimulating hormone. We posit that these differences predispose these animals to increased risks of disease and reproductive dysfunction at adulthood. PMID- 22061624 TI - Rapamycin inhibiting Jurkat T cells viability through changing mRNA expression of serine/threonine protein phosphatase 2A. AB - AIMS: In this study, we analyzed the mRNA expression of serine/threonine (Ser/Thr) protein phosphatase 2A (PP2A) in the human leukemic T-cell line Jurkat cells treated with rapamycin, to determine whether rapamycin inhibiting cell viability is accompanied with the change of mRNA expression of PP2A. METHODS AND RESULTS: Jurkat cells were incubated with various concentrations of rapamycin and cultured for different hours. Cell viability was assessed by MTT assay. The mRNA expressions of PP2A subunits were measured by quantitative real-time polymerase chain reaction (PCR). We found that rapamycin had an inhibitory effect on cell viability. IC50 was 343.3 nM at 48 h.We also found rapamycin had a dose and time dependent effect on the gene expression of PP2A. When setting the concentration of rapamycin 500 nM, the mRNA expressions of PP2A subunits (Aa, Abeta, PR55a, PR55delta, PR61gamma, PR70, Ca and Cbeta) were declined significantly at 48 h. When treated with various concentrations of rapamycin for 48 h, the mRNA expressions of PP2A subunits were down-regulated in the range from 10 nM to 500 nM. CONCLUSIONS: Rapamycin inhibiting Jurkat T cells viability may be related to the reduction of PP2A mRNA expressions. PMID- 22061625 TI - Centralised bulk pre-packaging of fresh pork retail cuts in various gas atmospheres. AB - A centralised bulk pre-packaging technique (laboratory method), utilising various gas mixtures (c. 100% CO(2); c. 75% CO(2):25% N(2); c. 80% O(2): 20% CO(2) and c. 25% CO(2):50% N(2):25% O(2)), was evaluated in terms of quality attributes such as microbiology, colour, odour and consumer acceptability. According to the bacterial counts recorded, all four packaging treatments were successful in prolonging the storage life (21 days c. 0 degrees C) of centralised bulk pre packaged pork retail cuts, while still ensuring a subsequent shelf life of at least 3 days (c. 0 degrees C). The gas mixture comprising c. 25% CO(2):50% N(2):25% O(2) was the most successful treatment in terms of acceptability and colour scores. PMID- 22061626 TI - Cholesterol oxidation in muscle tissue. AB - Three model systems were designed to monitor the oxidative stability of cholesterol in different lipid environments. The cholesterol moiety of cholesteryl linoleate oxidized to a greater extent than that of cholesteryl stearate and free cholesterol. Cholesterol oxidized when dispersed with either phosphatidyl choline or adipose tissue, further demonstrating that cholesterol oxidation is affected by the surrounding lipid environment. Oxidation of cholesterol in muscle tissue was also affected by the membrane environment. Vitamin E supplementation of veal calves improved the oxidative stability of muscle lipids and cholesterol. Comparison was made of the oxidative stability of retail beef lipids, including cholesterol, with the oxidative stability of veal lipids and cholesterol. The results supported the hypothesis that if initiation of lipid oxidation occurs in the muscle membranes, the fat content of the meat should not influence the stability of the lipids to initial oxidation. PMID- 22061627 TI - Effects of exogenous porcine somatotropin on the development of fat cells and fatty acid composition in backfat of live finishing pigs. AB - The effects of long-term application of recombinant porcine somatotropin (pST) to Landrace pigs on the development of backfat thickness, fat cells and fatty acid composition were investigated from about the 116th to the 186th day of life. Biopsy samples from the backfat of 56 castrates were taken at the beginning of treatment and after 5 and 10 weeks. The daily injection of 2 or 4 mg of pST induced a considerable decrease in backfat growth compared to untreated controls. This was attributed to a decreased size (about 18-20%) and number (about 13-25%) of fat cells. The higher dose of 4 mg pST/day induced a greater restriction of fat growth. This was obviously based on differences in fat cell number. Furthermore, pST treatment delayed the normal decrease of unsaturated fatty acids (C 18:2; C 18:3) during the period of growth examined. Therefore, the percentages of unsaturated fatty acids increased, indicating changes in fat cell metabolism of pST treated pigs. PMID- 22061628 TI - Quantitative determination of type I myosin heavy chain in bovine muscle with anti myosin monoclonal antibodies. AB - Bovine type I muscle fibers were characterized by enzyme-linked immunosorbent assay (ELISA) with a monoclonal antibody specific for slow myosin heavy chains (MHC 1). Two bovine muscles, the Masseter and Cutaneus trunci, were analyzed by different complementary techniques: electrophoresis, immunoblotting and immunohistiology. The results showed that the two muscles have extreme characteristics. The Masseter contains only slow MHC and the Cutaneus trunci is composed solely of rapid MHC (MHC 2a and 2b). A standard for this ELISA was obtained by mixing the two muscles and was used as a reference in the determination of the percentage of MHC 1 in a given muscle. In this study, the Longissimus thoracis of 27 Charolais cattle were examined. The different conditions under which assays were carried out were described and the accuracy of the measurement was calculated. In view of the results, ELISA was chosen for the analysis of muscle fiber types in large numbers of animal specimens. This technique could be used in several research projects to study the muscle characteristics that determine beef quality. PMID- 22061629 TI - The influence of high post-mortem temperature and differing ultimate pH on the course of rigor and ageing in pig Longissimus dorsi muscle. AB - This study was performed in order to assess the effect of temperature and differing ultimate pH (pH(u), 24 h post mortem) on the development of rigor mortis in pig Longissimus dorsi muscle. The rigor development (isometric tension and shortening) was measured continuously during the first 24 h post mortem, using an apparatus wherein muscle strips were held at constant temperatures of 12 or 35 degrees C. pH(u) was manipulated by adrenaline injections preslaughter. The rates of pH fall, adenosine triphosphate (ATP) and creatine phosphate (CP) breakdown were markedly increased at 35 degrees C compared to 12 degrees C. For both temperatures, no delay phase was observed with regard to the development of shortening. Rigor resulted in higher maximum isometric tension and shortening and in shorter time needed to reach maximum values at 35 degrees C than at 12 degrees C. The results are discussed in connection with pH, ATP and CP data. The extent of ageing from 2 to 4 days post mortem, estimated through myofibrillar length determinations, was higher for 12 degrees C than for 35 degrees C. pH(u) affected significantly most of the traits under study, but its effect depended in some cases upon the rigor temperature. At 12 degrees C, the traits related to the kinetics of rigor development were significantly affected by pH(u), but this was not the case at 35 degrees C. Maximum isometric tension was significantly related to pH(u) at 35 degrees C (r = 0.86, P < 0.001), but such a relationship was not found at 12 degrees C. Myofibrillar lengths were significantly affected by pH(u), but in an opposite manner from one temperature to another. A positive relationship was found at 12 degrees C and a negative one at 35 degrees C. These results illustrate the importance of the interaction between the extent of pH fall and temperature with regard to post-mortem changes in pig muscle. PMID- 22061630 TI - A traditional intermediate moisture meat: Beef cecina. AB - Cecina is an intermediate moisture meat produced and consumed to a large extent in Mexico. Four samples of cecina coming from different States of this country, were tested for water activity, colour, texture, fat, protein, moisture and chloride content. Sensory and microbiological analyses were also performed. Different fabrication methods for producing cecina were identified, involving large variations in the formulation of the product. There was a significant difference (P < 0.05) among samples regarding fat and chloride content, colour and texture. Differences in colour and saltiness were recorded through sensory analysis. Microbiological analysis showed higher counts than those recommended in the Mexican Official Standard for chopped and raw meat, due to poor sanitary conditions during production and marketing. PMID- 22061631 TI - Improvement of shelf-life and wholesomeness of ground beef by irradiation-2. Chemical analysis and sensory evaluation. AB - Lean ground beef was exposed to three dose levels of gamma radiations (Cobalt-60) (1.0, 2.5 and 5.0 kGy). Chemical indices monitored throughout the storage period (16 days, 4 degrees C) included pH, free fatty acids and peroxides. Irradiation clearly contributed to a diminution of the pH and an increase of the peroxides. Free fatty acids were not affected. The 10 non-expert panellists indicated a noticeable effect of irradiation on the odour and colour of the raw product. The odour and flavour of the irradiated cooked ground beef was slightly disliked while no difference was perceived in the colour and texture of the cooked irradiated ground beef. Following these considerations, it is recommended that ground beef be treated with a low dose (such as 1 kGy). PMID- 22061632 TI - The effective product life of vacuum-packaged beef imported into Saudi Arabia by sea, as assessed by chemical, microbiological and organoleptic criteria. AB - Five transport and storage trials were conducted on commercial shipments of vacuum-packaged beef half striploins imported into Saudi Arabia by sea from Australia, New Zealand and the Republic of Ireland. The cold chains, from packaging to the end of chilled storage in Saudi Arabia, were monitored using miniature electronic data loggers placed in cartons of striploins. Development of spoilage microfloras was followed from packaging to trial end using a differential aerobic plate count technique. Changes in meat pH, total volatile nitrogen (TVN) and free fatty acid (FFA) content were determined over the storage period. Sensory evaluations to identify spoilage conditions and to determine consumer acceptability were also conducted over the course of storage in Saudi Arabia. Results indicated that aerobic plate counts, TVN and FFA were all unsuitable as indicators of the fitness, or acceptability of vacuum-packaged beef for human consumption. Under good but commercially realistic conditions (i.e. normal ultimate pH beef, initial microbial contamination at packaging of less than 10(3)/cm(2), packaging, film oxygen transmission rate less than 40 ml/m(2)/24 h/atm at 23 degrees C and 90% R.H., and mean product temperature during transport and storage of 0 degrees C), vacuum-packaged beef transported by sea has an anticipated product life of at least 90 days measured from the date of slaughter. Under the conditions just stated, deterioration of meat texture resulting from excessive aging rather than the onset of overt microbial spoilage will limit the effective product life of vacuum-packaged beef. PMID- 22061633 TI - Oxymyoglobin formation in meat and poultry. AB - The rate of oxymyoglobin formation (blooming) was estimated, by reflectance spectrophotometry and depth of oxygen penetration, of beef and pork 1. dorsi and chicken breast muscles of normal ultimate pH. Although beef bloomed very rapidly when exposed to air, even at 23 degrees C, pork muscle exhibited little evidence of oxymyoglobin formation at this temperature and no chicken muscle produced oxymyoglobin at 23 degrees C. Even after 48 h at 5 degrees C there was little evidence of oxymyoglobin formation in the chicken muscles although formation was evident in the pork samples. After only 24 h storage at 5 degrees C it was apparent that both the chicken and pork muscles oxidised to produce some metmyoglobin at their surface, though the amount produced was apparently more in the chicken than the pork samples. In most chicken samples held in air at 5 degrees C the predominant pigments were the purple reduced myoglobin and brown metmyoglobin. The implication of these observations in relation to the packaging of chicken portions is discussed. PMID- 22061634 TI - Molecular forces involved in the formation and stabilization of heat-induced actomyosin gels. AB - Increasing concentrations of KCl, KF and NaCl from 0.2 to 1.0 m increased the compressive strength and cohesiveness of heat-induced actomyosin gels (0.6 m KCl pH 6.0). On the other hand, KBr, KSCN, KI, NH(4)Cl, MgCl(2) and CaCl(2) decreased gel strength and cohesiveness. Gel compressive strength increased with increasing urea concentration (0.4-2.4 m). Addition of the sulphydryl blocking agent N ethylmaleimide and the reducing agents dithiothreitol and cysteine decreased the compressive strength and cohesiveness of actomyosin gels. Overall, the results indicate that hydrophobic interactions, disulphide and hydrogen bonding contribute to the formation and stabilization of actomyosin gels. PMID- 22061635 TI - Analysis of meat pigments with tissue spectrophotometer TS-200. AB - The colour of meat and rice flour pastes containing known amounts of myoglobin and the colour of intact beef and pork samples were analyzed with tissue spectrophotometer TS-200. The differences in the spectra of myoglobin among three types of derivatives were successfully distinguished with this instrument. In addition, there is a close relationship between I(HB) value, a parameter for estimating the content of pigments in animal tissues, and myoglobin content in model systems (rice flour paste and meat paste). Especially, the I(HB) value is proportional to myoglobin content in intact beef and pork meat whose myoglobin is mostly in the state of oxymyoglobin and/or deoxymyoglobin: y = 208.26 x + 6.72, where y is the I(HB) value, x is the myoglobin content (%) and r = 0.94. PMID- 22061636 TI - Rabbit growth, feed efficiency and body composition: Effects of recombinant porcine somatotropin. AB - The effects of recombinant porcine somatotropin (rpST) were studied on rabbits from INRA 1077 strain, between the ages of 70 and 90 days. Ten rabbits received a daily intramuscular rpST injection (100 mg per day per kg of live weight) and were compared with ten control rabbits. Growth rate and feed efficiency were not affected by treatment. Perirenal fat deposits were smaller in rpST-treated than in the control rabbits (2.01 vs 2.72%) as were reference carcass lipid content (9.4 vs 10.8) and energy value (0.84 vs 0.88 MJ /100 g). The ratio between polyunsaturated fatty acids (FA) and saturated and monounsaturated FA was higher (0.32 vs 0.28). Reference carcass protein content was increased (20.5 vs 19.9%), as was the percentage of skin in slaughter weight (14.3 vs 13.4%). Muscular ultimate pH (24 h post mortem) was lower in the semimembranosus accessorius (5.67 vs 5.78) and in the biceps femmoris (5.65 vs 5.74) of treated rabbits. In conclusion, rpST, as a heterologous hormone, develops protein-rich tissues whilst lowering fat content and appears to affect the balance of muscular energy metabolism. PMID- 22061638 TI - Efficient synthesis of a novel m-phenylene derivative as a selective EP4 agonist inducing follicular growth and maturation in the ovary. AB - An efficient and straightforward synthesis of a novel m-phenylene derivative has been developed. The optically pure dibromo compound was selected as a starting material. Through a protocol involving the Prins reaction and two steps of the Horner-Wadsworth-Emmons reaction, the basic skeleton was constructed with appropriate alpha and omega side chains. The compound proved to be a highly selective EP(4) agonist and a possible drug candidate for maturation of the uterine cervix. PMID- 22061639 TI - Discovery, optimisation and in vivo evaluation of novel GPR119 agonists. AB - GPR119 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. During a programme aimed at developing agonists of the GPR119 receptor, we identified compounds that were potent with reduced hERG liabilities, that had good pharmacokinetic properties and that displayed excellent glucose-lowering effects in vivo. However, further profiling in a GPR119 knock-out (KO) mouse model revealed that the biological effects were not exclusively due to GPR119 agonism, highlighting the value of transgenic animals in drug discovery programs. PMID- 22061640 TI - Discovery of 4-aminomethylphenylacetic acids as gamma-secretase modulators via a scaffold design approach. AB - Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid gamma-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable gamma-secretase modulation profile. Scaffold optimization led to the discovery of a novel chemical series, represented by 6b, having improved brain penetration. Further SAR studies provided analog 6q that exhibited a good pharmacological profile. Oral administration of 6q significantly reduced brain Abeta42 levels in mice and rats. PMID- 22061641 TI - The discovery of novel cyclohexylamide CCR2 antagonists. AB - As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation. PMID- 22061642 TI - Efficient synthesis and in vitro antitubercular activity of 1,2,3-triazoles as inhibitors of Mycobacterium tuberculosis. AB - Efficient and rapid synthesis of 1,2,3-triazole derivatives has been achieved via Huisgen's 1,3-dipolar cycloaddition between alkyl/arylazides and diethyl/dimethyl acetylenedicarboxylate in excellent yields under solvent-free conditions. The environmentally friendly solvent-free protocol overcomes the limitations associated with the prevailing time-consuming solution phase protocols and affords the triazoles just in 1-3 min. In vitro antitubercular activity of these triazoles was screened against Mycobacterium tuberculosis H(37)Rv strain. Four of the compounds showed MIC in the range of 1.56-3.13 MUg/mL proving their potential activity. PMID- 22061643 TI - Synthesis and antihepatotoxic activity of 5-(2,3-dihydro-1,4-benzodioxane-6-yl)-3 substituted-phenyl-4,5-dihydro-1H-pyrazole derivatives. AB - In continuance of our search for newer antihepatotoxic agents some novel pyrazoline derivatives containing 1,4-dioxane ring system were synthesized starting from 3-(2,3-dihydro-1,4-benzodioxane-6-yl)-1-substituted-phenylprop-2-en 1-one. Some of the synthesized compounds were evaluated for antihepatotoxic activity against CCl(4)-induced hepatotoxicity in rats. Among them some compounds have shown significant antihepatotoxic activity comparable to standard drug silymarin. PMID- 22061644 TI - Investigation of the diastereomerism of dihydrobenzoxathiin SERMs for ER alpha by molecular modeling. AB - Molecular dynamics simulations were performed to investigate the distinct uterine activity of ten dihydrobenzoxathiin diastereomers against human estrogen receptor (ER) alpha. These diastereomers share similar binding mode to ER alpha ligand binding domain (LBD). Dihydrobenzoxathiin diastereomers with full antagonistic activity form more stable hydrogen bonds with Glu353 and His524 of ER alpha LBD than corresponding diastereomers. The molecular mechanics based generalized born surface area (MM-GBSA) analysis revealed that van der Waals interactions are predominant to the binding of dihydrobenzoxathiin diastereomers to ER alpha LBD. The per-residue free energy decomposition analysis revealed that the uterine activity difference is contributed mainly by electrostatic interactions. Our study provides mechanistic insights into the difference of uterine activity for dihydrobenzoxathiin diastereomers. PMID- 22061645 TI - Pyrazolone-based anaplastic lymphoma kinase (ALK) inhibitors: control of selectivity by a benzyloxy group. AB - Anaplastic lymphoma kinase (ALK) is transmembrane receptor tyrosine kinase, with oncogenic variants that have been implicated in ALCL, NSCLC and other cancers. Screening of a VEGFR2-biased kinase library resulted in identification of 1 which showed cross-reactivity with ALK. SAR on the indole segment of 1 showed that a subtle structural modification (the ethoxy group of 1 changed to a benzyloxy to generate 5a) enhanced potency (ALK), selectivity for VEGFR2 and IR along with improvement in metabolic stability. From docking studies of ALK versus VEGFR2 kinase, we postulated that the loss of entropy of the VEGFR2 in the bound form with 5a might be the origin of the reduced activity against that protein. Modification of the heterocyclic segment showed that thiazole-bearing pyrazolones preserved enzyme potency, and enhanced inhibition of NPM-ALK autophosphorylation in ALK-positive ALCL cells (Karpas-299). SAR of the benzyloxy group resulted in compounds which demonstrated good cellular potency in Karpas-299 cells. Compound 8 showed best overall profile for the series with broad kinome selectivity and liver micorsome stability. Compound 8 showed reasonable iv PK in rat, but with little oral exposure. PMID- 22061646 TI - The effect of conditioning on the strength of perimysial connective tissue dissected from cooked meat. AB - Tensile tests were carried out on ribbons of perimysial connective tissue dissected from slices of bovine semitendinosus muscles that had been conditioned or not conditioned and then cooked to a range of temperatures. A consistent reduction in the strength of the perimysia was seen in the conditioned samples, both in the raw meat and meat cooked to 50 degrees C. At higher cooking temperatures (60-80 degrees C), no effect of conditioning was seen. The content of collagen or total protein of mechanically extracted perimysia and the collagen content of the test pieces from conditioned and unconditioned muscles was not significantly different. It was concluded that conditioning decreases the breaking strength of the perimysial connective tissue in raw meat or in meat which is subsequently cooked to 50 degrees C, but not in meat cooked to the temperatures normally employed by consumers. The tenderization observed in conditioned meat cooked to 60 degrees C and above is, therefore, due to the weakening of muscle fibres within the fibre bundles. PMID- 22061647 TI - Studies on the return of physical reflexes in pigs following electrical stunning. AB - In order to obtain quantitative information on the duration of insensibility in pigs (60-80 kg) following electrical stunning, experiments were carried out using 50 Hz alternating current for 3 and 7 s current durations at different voltages. The following features were examined: the mean current received by each pig, the period of loss of reflexes and the time to return of spontaneous activity, and cranial nerve reflexes. In particular the return of breathing was used as a first sign of recovery, and the response to a nose prick and presence of the righting reflex were used as indicators of overt consciousness. A minimum current in excess of 406 mA was required to effectively stun these pigs with sufficient duration of loss of reflexes. At least 150 V for 3 s current duration should be used and a maximum stunning to exsanguination interval of 15 s is considered sufficient to ensure pigs of this size do not regain consciousness following the stun. PMID- 22061648 TI - Monoclonal antibody sandwich ELISA for the potential detection of chicken meat in mixtures of raw beef and pork. AB - A sandwich ELISA (enzyme-linked immunosorbent assay) has been developed successfully for the detection of defined amounts of chicken meat (1-100%) in beef and pork meat mixtures. The assay uses a monoclonal antibody (BC9) specific to a chicken muscle soluble protein to capture this protein from complex meat mixtures. Further immunorecognition of the captured protein was attained with rabbit polyclonal antibodies against chicken muscle proteins (anti-CHSP). A commercial goat anti-rabbit immunoglobulin conjugated to peroxidase was used to detect the anti-CHSP antibodies bound to the chicken protein. Subsequent enzymic conversion of substrate gave clear optical density differences when assaying mixtures of beef and pork meats containing variable amounts of chicken meat. PMID- 22061649 TI - Serum skatole detection using gas chromatography and high performance liquid chromatography. AB - Skatole-spiked boar serum was used to evaluate the degradation of skatole during frozen storage and to evaluate gas chromatography (GC) and high performance liquid chromatography (HPLC) for measuring serum skatole. Tubes of serum spiked with 1 ppm skatole which had been stored in a freezer (-15 degrees C) for 4 months and tubes of fresh spiked serum (1 ppm skatole) were utilized. No differences (P > 0.05) between GC and HPLC determination in sensitivity and skatole recovery were observed. Measurements of skatole by GC and HPLC were highly correlated (r = 0.93). Both GC and HPLC revealed no difference (P > 0.05) between fresh spiked serum and stored spiked serum samples. PMID- 22061650 TI - Growth characteristics of meat starter cultures. AB - The Australian Code of Practice for manufacture of dry and semi-dry sausage (salami) states that fermentation temperatures must not exceed 25 degrees C and that a pH of 5.2 must be achieved in the product within 48 h. In order to select the most appropriate starter cultures for fermentation, Lactobacillus plantarum, Pediococcus pentosaceus and Staphylococcus carnosus were characterised with respect to growth and acid production determined at constant pH (4.7, 5.5 and 6.3). L. plantarum and P. pentosaceus showed similar characteristics over the pH range studied while S. carnosus was sensitive to lower pH. Also, P. pentosaceus showed greater psychrotrophic growth without pH control than L. plantarum or S. carnosus. Salami made with P. pentosaceus maintained higher viable numbers in the product over 8 days than did L. plantarum. Growth of S. carnosus in salami could not be detected in the presence of the more pH-tolerant organisms. The growth of L. plantarum and P. pentosaceus did not prevent the development of high levels of non-starter flora, a factor that can be important in determining salami quality. However, the more psychrotrophic P. pentosaceus ensured a greater dominance of starter over non-starter flora. PMID- 22061651 TI - Effect of cooking temperature on the percentage colour formation, nitrite decomposition and sarcoplasmic protein denaturation in processed meat products. AB - The effect of cooking temperature and time on the percentage colour formation, nitrite decomposition and denaturation of sarcoplasmic proteins in processed meat products was investigated in detail. The colour forming percentage increased with a rise in temperature of heating, especially at 50-60 degrees C (P < 0.05). The percentage nitrite decomposition was promoted by the retention time of cooking rather than by the cooking temperature (P < 0.05). The percentage of sarcoplasmic proteins denatured was enhanced by heating temperature in the range 50-80 degrees C (especially at 50-60 degrees C) (P < 0.05). The relationship between the percentage colour formation and the percentage of sarcoplasmic proteins denatured is discussed. The SDS-PAGE patterns of the heat-treated samples revealed the components of the sarcoplasmic proteins which had been denatured. PMID- 22061652 TI - Acceptability of low-fat frankfurters as influenced by the feeding of elevated levels of monounsaturated fats to growing-finishing swine. AB - The effects of high levels of oleic acid in the diet on the physical, chemical and sensory traits of frankfurters were examined. Frankfurters were formulated at three fat levels (10, 20 and 25%) from pork trimmings from each dietary treatment. The control frankfurters were the most springy, firm, flavorful and palatable and had the most intense flavor (P < 0.05). However, low-fat frankfurters produced from the high-oleate treatments were comparable to the control in all sensory characteristics (P > 0.05). The 10 and 25% fat frankfurters were rated highest and lowest, respectively, for juiciness, springiness, firmness, flavor, flavor intensity and overall palatability (P < 0.05). Sensory panelists detected off-flavors in the 25% fat frankfurters more frequently than in the 10% fat frankfurters (P < 0.05). 2-Thiobarbituric acid values were not affected by treatment and were acceptable after storage at 2 degrees C for 24 weeks (P < 0.05). PMID- 22061653 TI - Eating quality of meat from pigs given the beta-adrenergic agonist salbutamol. AB - Meat from pigs given the beta-adrenergic agonist Salbutamol was assessed by a trained taste panel. Overall, there were no significant effects of Salbutamol on panel scores for pork flavour, foreign flavour or overall acceptability. Although the differences were also not significant, meat from treated pigs was rated slightly tougher (P = 0.10) but more juicy (P = 0.14) than that from untreated animals. This concurred with higher instrumental values for toughness although the correlation between taste panel and instrumental texture measurements was low (r = 0.36, P < 0.001). PMID- 22061654 TI - An objective measure of muscularity: Changes with animal growth and differences between Genetic lines of southdown sheep. AB - A measure of muscularity, based on objective measurements, and expressed in terms of muscle depth relative to skeletal dimensions, is proposed and investigated using a simulation model. Average muscle depth is assessed as the square root of the muscle weight per unit length of a bone adjacent to the muscle. Muscularity is then defined as average muscle depth divided by bone length. Evidence based on a theoretical model, results from the literature and data from backfat selection lines of Southdown sheep is used to illustrate how muscularity defined in this way changes with growth, and the extent to which it parallels changes in muscle to bone ratio. It is concluded that although these two characteristics often change together there are situations where differences in muscularity are not accompanied by differences in muscle to bone ratio and vice versa. PMID- 22061659 TI - Enzyme-assistant extraction (EAE) of bioactive components: a useful approach for recovery of industrially important metabolites from seaweeds: a review. AB - Over the years, the biological activities of seaweeds could have gained a considerable research interest because of their specific functional compounds, which may not be available in land plants. Thus, efforts at discovery of novel metabolites from seaweeds over the past years have yielded a considerable amount of new active compounds. In addition, studies about the extraction of active compounds from natural products have attracted special attention in the last recent years. Potent biologically active compounds of seaweeds have been demonstrated to play a significant role in prevention of certain degenerative diseases such as cancer, inflammation, arthritis, diabetes and hypertension. Therefore, seaweed derived active components, whose immense biochemical diversity looks like to become a rich source of novel chemical entities for the use as functional ingredients in many industrial applications such as functional foods, pharmaceuticals and cosmeceuticals. Thus, the interest in the extraction of active compounds from seaweeds is obvious. However, the physical and chemical barriers of the plant material become the key drawbacks of such extraction process. Therefore, enhanced release and recovery of active compounds attached to the cells have been addressed. Taken together, the aim of this communication is to discuss the potential use of enzyme treatment as a tool to improve the extraction efficiency of bioactive compounds from seaweeds. PMID- 22061660 TI - Ginsenoside Rd stimulates the differentiation and mineralization of osteoblastic MC3T3-E1 cells by activating AMP-activated protein kinase via the BMP-2 signaling pathway. AB - As part of our search for biologically active anti-osteoporotic agents that enhance the differentiation and mineralization of osteoblastic MC3T3-E1 cells, we identified the ginsenoside Rd as the most active compound among ginsenosides. In this study, we showed that Rd stimulates osteoblastic differentiation and mineralization, manifested by the up-regulation of differentiation markers (alkaline phosphatase and osteogenic genes) and von Kossa/Alizarin Red staining, respectively. Rd induces the mRNA expression of bone morphogenetic protein-2 (BMP 2) and the secretion of the corresponding protein into media in a concentration dependent manner. The mRNA expression and enzyme activity of alkaline phosphatase (ALP) were suppressed when MC3T3-E1 cells were exposed to noggin, a BMP-2 antagonist. The level of phosphorylated AMP-activated protein kinase (pAMPK) protein was also up-regulated by Rd in a time- and concentration-dependent manner. Rd-induced ALP activity, mineralization, and BMP-2 production were all inhibited by either Ara-A (AMPK inhibitor) or siRNA targeting AMPK. In addition, we investigated whether Rd-induced BMP-2 transduces signals through the Smad signaling pathways. Rd induced a significant level of phosphorylation of Smad1/5, and this effect was blocked when the cells were transfected with siRNA targeting Smad4, indicating that Smad1/5 must form complex with Smad4 to translocate into the nucleus and regulate the transcription of osteogenic genes. In summary, these results indicate that Rd induces the differentiation and mineralization of MC3T3 E1 cells through the activation of the AMPK/BMP-2/Smad signaling pathways. These findings provide a molecular basis for the osteogenic effect of Rd in MC3T3-E1 cells. PMID- 22061661 TI - A new 9-nor-atractylodin from Atractylodes lancea and the antibacterial activity of the atractylodin derivatives. AB - A new compound, namely, 9-nor-atractylodin (1) and one known atractylodin (2) were isolated from the rhizomes of Atractylodes lancea. The structural modifications of atractylodin were carried out and a series of atractylodin derivatives (3-10) were obtained. The antibacterial activities of 1-10 were examined against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Candida albicans. Compounds 4 and 8, which contained the alpha, beta-unsaturated carbonyl fragment, were found to be active against E. coli and S. aureus. PMID- 22061662 TI - Polyketides with antimicrobial activity from the solid culture of an endolichenic fungus Ulocladium sp. AB - Two new polyketides, 7-hydroxy-3, 5-dimethyl-isochromen-1-one (1) and 6-hydroxy-8 methoxy-3a-methyl-3a,9b-dihydro-3H-furo[3,2-c]isochromene-2,5-dione (2), along with eleven known compounds, 5'-methoxy-6-methyl-biphenyl-3,4,3'-triol (3), 7 hydroxy-3-(2-hydroxy-propyl)-5-methyl-isochromen-1-one (4), rubralactone (5), isoaltenuene (6), altenuene (7), dihydroaltenuenes A (8), altenusin (9), alterlactone (10), 6-O-methylnorlichexanthone (11), norlichexanthone (12), and griseoxanthone C (13) were isolated from the culture of the endolichenic fungus Ulocladium sp. Compound 2 was obtained as a racemate with an unprecedented chemical skeleton. The NMR data assignments for 3 and 4 were achieved for the first time. Compounds 1-13 were screened for their antimicrobial and radical scavenging activities. Compound 1 showed some antifungal activity against Candida albicans SC 5314 with IC(50) of 97.93 +/- 1.12 MUM. Compounds 11-13 showed strong activity against Bacillus subtilis with IC(50) in the range of 1-5 MUM. Compound 12 significantly inhibited the growth of methicillin-resistant Staphylococcus aureus with IC(50) of 20.95 +/- 1.56 MUM. Compounds 9 and 10 showed strong radical scavenging activity in comparison with vitamin C. The plausible biosynthetic pathways for compounds 1, 2, and 4-8 were discussed. PMID- 22061663 TI - Proteomics advances in the last decade: What is next? PMID- 22061664 TI - A comparison of subcutaneous adipose tissue proteomes in juvenile piglets with a contrasted adiposity underscored similarities with human obesity. AB - Subcutaneous fat tissues from an indigenous fat-type breed and an intensively lean selected breed were studied in juvenile pigs. Combining DIGE with bioinformatics and target analyses of key genes, enzymes or terminal routes, this study identifies metabolic and homeostatic processes, response to organic substances, and acute-phase responses as the main pathways whose proteins were regulated in association with adiposity. Breed-related differences in abundance and activities of malic enzyme and glucose-6-phosphate dehydrogenase NADPH supplying enzymes suggested up-regulation of the lipogenic pathway to dispose for a greater adiposity. Over-abundance in the lipolytic protein carboxylesterase-1 was revealed in fat-type piglets. A panel of pro- and anti-inflammatory proteins such as serpins, had an altered abundance in the fat-type piglets, suggesting adverse consequences of fat accumulation even in early post-weaning stages. Propensity to low-grade inflammation in fat pigs was reinforced by the up regulation of genes encoding pro-inflammatory cytokines IL6 and TNF-alpha in these piglets. Differential abundance in annexin-A5 and pericentrin suggested a positive regulation of cell apoptosis in lean piglets. Our results are relevant in the context of data linking the accretion of body lipids to the physiology and pathology of adipose tissue in models other than rodents for a better control of human health and nutrition. PMID- 22061665 TI - Cell surface hydrophobicity and attachment of pathogenic and spoilage bacteria to meat surfaces. AB - Cell surface hydrophobicity of several pathogenic and spoilage bacteria was determined by hydrocarbon adherence, adhesion to nitrocellulose filter, salt aggregation and adherence to phenyl-sepharose beads. Hydrophobicity of each bacterium was dependent on the method of measurement. Hydrophobicity was compared with the strength of attachment (Sr) of the bacteria to beef muscle surfaces. Bacterial cell surface hydrophobicity, as determined by the bacterial adherence to xylene correlated well with attachment strength (r = 0.800, P < 0.05). Staphylococcus aureus, Clostridium perfringens and Yersinia enterocolitica showed the highest values of attachment strength. PMID- 22061666 TI - Chilled storage life of hot-boned, pre-rigor, salted minced beef. AB - Pre-rigor beef mince with 2% added salt was stored under CO(2) at -1.5 degrees C (A). The same mince with 100 ppm sodium nitrite was stored under CO(2) at 5 degrees C (B) and -1.5 degrees C (C), and under vacuum at -1.5 degrees C (D). Microbiological and sensory analyses were carried out for up to 21 weeks. Indicative storage life was taken as the time for microbial numbers to reach 10(7) colony forming units per g. Mince stored under regimes B or D attained these numbers by 6 and 14 weeks, respectively; mince stored under regimes A and C had not attained these numbers by the end of the storage trial. Mince stored at 5 degrees C developed storage flavours of sufficient intensity to be detectable by consumers by 9 weeks storage. In general, the other minces did not develop unacceptable levels of storage or off flavours. Over 90% of the added sodium nitrite had disappeared after 10 weeks of storage, partly through conversion to sodium nitrate. Mince pH was not affected by the storage conditions and remained at about 6.0. The water holding capacity of the pre-rigor mince deteriorated during prolonged storage. PMID- 22061667 TI - Differences in composition, muscularity, muscle:bone ratio and cut dimensions between six lamb genotypes. AB - Carcass measurements and composition data were obtained for 198 lambs representing two sexes (104 cryptorchids, 94 ewes). Dorsal images of 166 of the carcasses were obtained on the slaughter chain using a video camera. The lambs were sired by a selection of Poll Dorset (PD), Texel (T), Border Leicester (BL) and Merino (M) rams, born to Border Leicester * Merino (BLM) and Merino (M) ewes giving 6 genotypes (PD * BLM, T * BLM, PD * M, T * M, BL * M, M * M). From the right hindleg and chump, the following muscles were dissected and weighed: semimembranosus, adductor femoris, semitendinosus, biceps femoris, and quadriceps femoris. The femur was weighed, the length measured and a muscularity value calculated as described by Purchas, et al. (1991, Meat Sci., 30, 181). Merino cryptorchid lambs were significantly (P < 0.05) leaner, as measured by GR tissue depth (for explanation, see MATERIALS AND METHODS) adjusted to a mean carcass weight of 24.2 kg, than BL * M lambs, but there was no difference between genotypes within the ewe group (mean carcass weight of 17.1 kg). Genotype differences were found for conformation using the EUROP scoring system. Merino lambs had a greater proportion (P < 0.001) of poorer scores, particularly compared to PD * BLM and T * BLM carcasses. The BL * M carcasses had a significantly (P < 0.05) smaller m. longissimus thoracis et lumborum area than other genotypes with no difference between carcasses of T and PD sires. Muscularity values for the BL * M and M lambs were significantly (P < 0.05) lower than the other crosses but not different from each other. Carcasses from T sires had significantly (P < 0.05) higher muscularity values than those from PD sires. A negative association (r = -0.56) was found between EUROP scores and muscularity when carcass differences were adjusted for, but significant differences between genotypes for muscularity were not necessarily carried through to differences in EUROP conformation score. BL * M carcasses had the lowest muscle:bone ratio and T * M the highest with M carcasses having similar ratios to carcasses from PD-sired lambs. Only small differences were found between genotypes for composition of the hindleg, the exception being BL * M carcasses of both sexes which were significantly (P < 0.05) fatter than T * BLM, T * M and PD * M carcasses. Carcasses from T sires had significantly (P < 0.05) more muscle in the hindleg than carcasses from PD sires, with the differences being greater in the heavier cryptorchids (1.8%) than the ewes (1.1%). There was no consistent effect of genotype on the cross-sectional areas of the round and topside cuts within either sex. Differences between genotypes for the proportion of the carcass attributed to the round were small and only for BL * M ewe carcasses was this cut significantly lighter (P < 0.05) than from all other genotypes, except the PD * BLM carcasses. This trend was similar for the topside and silverside cuts. A moderate correlation (r = 0.46; P < 0.001) was found between muscularity values determined by dissection and those predicted using the equations of Hopkins et al. (1996, Proc. Aust. Soc. Anim. Prod., 21, 181) based on carcass width measurements taken from video images. PMID- 22061668 TI - Proteasome from rabbit skeletal muscle: Some properties and effects on muscle proteins. AB - Rabbit proteasome, likely to be a 20S proteasome, was purified and its properties were investigated to clarify its contribution to proteolysis during meat conditioning. The purified enzyme migrated as a single band on non-denaturing polyacrylamide gel and dissociated to a number of subunits (20000-29000 Da) under denaturing conditions. The molecular mass of this enzyme was found to be 580 000 800 000 Da by Sephacryl S-300 column chromatography. The isoelectric point of this enzyme was 5.5. The optimum pH for hydrolysis of succinyl-Leu-Leu-Val-Tyr-(4 methylcoumaryl-7-amide) (Suc-LLVY-MCA) was 8. This enzyme was almost stable in the range of pH 5-9 and up to 60 degrees C at pH 7.2. The enzyme activity was inhibited by diisopropyl fluorophosphate (DFP) and chymostatin, but was not affected by EDTA, leupeptin, E-64, bestatin, monoiodoacetic acid or pepstatin. The enzyme was activated about 8-fold by 0.01% sodium dodecyl sulfate (SDS), but was not by ATP or CaCl(2). Remarkably, SDS increased the V(max) value of the enzyme. Rabbit proteasome was shown to degrade myosin heavy chain, alpha-actinin, actin, tropomyosin, troponins and myosin light chains in the presence of SDS. In the absence of SDS, no change in myofibrillar proteins was observed. This enzyme did not degrade any sarcoplasmic proteins regardless of the presence of SDS. PMID- 22061669 TI - Effect of pH at time of salting on the functional properties of pre-rigor beef. AB - The functional properties of thawed pre-rigor beef that had been minced and salted or not salted when its pH value reached 6.8, 6.6, 6.4, 6.2 and 6.0, then immediately frozen, were determined. The mince samples were used to manufacture a finely comminuted sausage batter. Presalting before frozen storage resulted in higher (p < 0.05) thawed mince pH, and batter cook yield and shear strain, and lower (p < 0.05) mince salt soluble proteins, thaw drip and Hunter L(*) and b(*) values and batter shear stress than unsalted controls. The pre-rigor pH at time of salting/mincing affected (p < 0.05) thaw drip (unsalted mince only), Hunter L(*) and b(*) values and shear stress. Shear stress tended to increase (p < 0.01) and Hunter L(*) (p < 0.05) and b(*) (p < 0.01) values tended to decrease with fall in pre-rigor salting pH. No interaction (p > 0.05) between salting and pre rigor pH at time of salting was observed. PMID- 22061670 TI - Assessment of the role of meat cut on the Fe, Zn, Cu, Ca and Mg content and their in vitro availability in homogenised weaning foods. AB - The aim of the present study was to compare the Fe, Zn, Cu, Ca and Mg contents and their in vitro availability in three meat-based weaning foods as a function of the meat cuts used in their formulation. The three meat cuts were yearling cow flank (YCF), mature cow flank(MCF) and mature cow mixed (MCM) cuts. The highest level of Fe (1.14 +/- 0.31 mg/100 g) was obtained in MCM weaning food, whereas the highest content of Zn (0.96 +/- 0.05 mg/100 g) was detected in YCF weaning food, depending significantly on the meat cut used (p < 0.05 and p < 0.001, respectively). Cu, Ca and Mg contents were similar in the three weaning foods analysed. Amounts of dialysed minerals were higher in flankbased weaning foods YCF and MCF, with the exception of Ca which was higher in MCM. In addition, it is important to emphasise the high percentage of available Fe observed in MCF weaning food (8.57%) compared with the other two, 6.37% for YCF and 4.90% for MCM. PMID- 22061671 TI - Simultaneous detection of a sex-specific sequence and the Ryr1 point mutation in porcine genomic DNA. AB - The advantages are becoming increasingly apparent of designing livestock breeding programmes around the detection of specific sequences in genomic DNA using amplification by the polymerase chain reaction (PCR). Furthermore, by subjecting the products of such reactions to restriction enzyme digestion, important information conveyed by single-base substitutions can be retrieved and used in marker-assisted selection. The potential for the rapid diagnosis of several DNA markers simultaneously would seem to offer particular benefits in the field of in vitro fertilisation and embryo transfer, where only a few cells constitute the source of the DNA, and where keeping the duration of the tests to a minimum is imperative. However, where the markers to be detected fall into different categories, different kinds of amplification reactions may need to be combined. The present study with porcine DNA combines a one-step multiplex PCR test for sex determination with a specialised PCR reaction designed to diagnose the Ryrl or 'halothane' genotype. A total of seven primers have been utilised to amplify by, firstly, a control sequence related to the Zfx/y genes present in both sexes, secondly to amplify a Y chromosome sex-specific sequence related to the Sry gene and lastly, to detect either allele of the Ryr1 mutation associated with porcine stress syndrome and pale, soft exudative meat. The presence of PCR products of characteristic size on agarose gel electrophoresis gives a visual read-out of animal sex and halothane genotype. Although primarily a model system, the test may have direct applications in the context of embryo transfer, sperm separation technology and also in the characterisation of pork samples undergoing sensory evaluation by meat scientists. PMID- 22061672 TI - Effects of dietary alpha-tocopheryl acetate supplementation on alpha-tocopherol deposition in porcine m. psoas major and m. longissimus dorsi and on drip loss, colour stability and oxidative stability of pork meat. AB - The effect of feeding supra-nutritional levels of alpha-tocopheryl acetate on its deposition in two porcine muscles of different metabolic rates (m. longissimus dorsi and m. psoas major) and the effect on meat quality (lipid oxidation, colour stability and drip loss) was studied. Pigs were fed a standard diet supplemented with three levels: 100, 200 and 700 mg/kg of alpha-tocopheryl acetate from the time of weaning to slaughter at 90kg live weight. Muscle alpha-tocopherol levels were linearly related to the logarithm of dietary alpha-tocopheryl acetate supplementation and the linear relationship was estimated for the two muscles. The levels of alpha-tocopherol in the two muscles differed by a parallel displacement with consistently higher alpha-tocopherol levels in m. psoas major compared to m. longissimus dorsi. Dietary alpha-tocopheryl acetate supplementation significantly reduced lipid oxidation as measured by thiobarbituric acid reactive substances (TBARS) in both raw and cooked meat during storage at 4 degrees C for 6 days. Drip loss and colour stability of raw muscles were not affected by dietary alpha-tocopheryl acetate levels, 100mg alpha tocopheryl acetate/ kg feed resulted in sufficient alpha-tocopherol levels in muscles to ensure minimum drip loss and optimum colour stability. PMID- 22061673 TI - Responses of two genotypes of chicken to the diets and stocking densities typical of UK and 'Label Rouge' production systems: I. Performance, behaviour and carcass composition. AB - 'Label Rouge' (LR) chickens are reputed to possess improved sensory characteristics compared with birds reared under intensive conditions. The effects on body weight, food utilisation, behaviour and carcass composition, of genotype (Ross I vs ISA '657'), diet (conventional UK broiler vs LR) and stocking density (17.0 birds m(-2),vs 4.25 birds m(-2)) were evaluated in a 2 * 2 * 2 experiment. ISA birds were grown to 83 days, and compared with Ross birds grown to 48 days; additionally ad libitum and control-fed Ross birds were grown to 83 days. Performance and behaviour parameters were assessed empirically. The effects on carcass composition were evaluated using standardised carcass dissection techniques and analysed by analysis of variance. ISA birds grown under LR conditions to 83 days had similar body weights to Ross birds grown under UK broiler conditions to 48 days, but LR birds consumed more food, and converted food into meat less efficiently. LR birds had no mortality, whilst UK broiler mortality was 11.3%. Under similar conditions, Ross birds had a faster body weight gain, a larger food intake, but more efficient food conversion ratio and higher incidence of mortality. Birds stocked 17.0 m(-2) had lower body weights, consumed less food and, when fed UK diets, converted food less efficiently than birds stocked 4.25 m(-2). Both genotypes had a faster growth rate on UK diets, similar food intakes, and, as a result, better food conversion than birds given LR diets. LR and UK broiler birds had similar carcass component weights, breast meat yields, and total meat yield, but LR birds had less meat on the frame, larger drumsticks and more meat on the wings. Under similar conditions, ISA birds had a larger percentage of wing and total bone, but a smaller percentage of breast meat and total meat yields. When Ross birds had controlled growth, total meat, bone and skin yields were similar to those of ISA birds. Birds stocked 4.25 m(-2) had more breast meat and larger frames than, but similar meat, bone and skin yields to, birds stocked 17.0 m(-2). Most carcass components were heavier in birds fed UK broiler diets, but, on a percentage basis, these birds had larger thighs, but smaller drumsticks. PMID- 22061674 TI - The effects of Ca ions, EGTA and storage time on myofibrillar protein degradation, levels of Ca(2+)-dependent proteases and cathepsins B, H, L and D of ostrich skeletal muscle. AB - The effect of Ca ions and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N' tetraacetic acid (EGTA) on myofibrillar protein degradation showed that when ostrich iliotibialis lateralis muscle was incubated with 10 mM EGTA at 2-4 degrees C for 24 hr, the activity of extracted cathepsin H was unchanged compared with a buffer-incubated sample. Ca(++) had no effect on extracted cathepsin H activity, while that of Ca(2+)-dependent protease (CDP) decreased significantly (p < 0.05). Ca(2+)-treatment enhanced post-mortem changes observed in myofibrillar protein patterns (production of fragments around 30 K) that were not observed in EGTA-incubated myofibrils. The effect of storage time on shear force, CDP activity, cathepsin B, D, H and L activities and the SDS-PAGE pattern of myofibrils showed a time-dependent reduction in CDP activity. Of the cathepsins studied only cathepsin H showed a reduction (40%) in activity. The most prominent component appearing on storage at 2-4 degrees C had a M(r) of 27 K. The incubation of myofibrils with CDP mimicked the post-mortem changes. CDP may be responsible for some of the post-mortem changes observed, although shear force measurements suggest these changes do not lead to significant tenderisation. PMID- 22061675 TI - Improving the flavor of calcium chloride and lactic acid injected mature beef top round steaks. AB - The effect of added commercial beef flavoring on the physical and sensory characteristics of CaCl(2) and lactic acid injected cow meat was investigated. A 10% injection of 0.3 M CaCl(2) and 0.3 M lactic acid into hot-boned top rounds (m. semimembranosus) decreased shear forces over traditional top round steaks. The addition of commercial beef flavoring (4% solution) to the CaCl(2) and lactic acid injection did not alter the resulting pH, cook loss or total aerobic plate count (APC) of injected steaks. However, beef flavoring did increase the beef/brothy and oniony aromatics and salt taste, and decreased the soured and medicinal aromatics and bitter tastes of hot-boned, CaCl(2) and lactic acid injected top round steaks. PMID- 22061676 TI - Colour parameters of Turkish-type fermented sausage during fermentation and ripening. AB - Colour parameters of Turkish-type fermented sausage during fermentation and ripening were evaluated. CIE x y, L(*) a(*) b(*), C(*) h degrees , pigment nitrosation (NI) and pigment discoloration (RSI) were measured. Sausage processing had four stages consisting of first and second fermentation steps and then two consecutive ripening steps. Variations of colour parameters with processing indicated that Turkish-type fermented sausage processing might be divided into two well defined phases from the colour point of view. Optimum colour was obtained at the end of the first ripening step. PMID- 22061677 TI - Characteristics of chicken-seal salami. AB - Mechanically separated seal meat (MSSM) at 10% (SM-10) and 20% (SM-20) or seal protein hydrolysate (SPH) at 1% (SPH-1) and 2% (SPH-2) prepared from MSSM were used to replace mechanically separated chicken meat (MSCM) in salami formulations. Cured products containing 10 or 20% MSSM had a deeper red colour than those of the controls as noted by Hunter L and a values. Samples containing 20% MSSM had a softer texture as determined by sensory and Kramer shear compression test studies, which was supported by scanning electron micrographs. All samples were equally acceptable as determined by sensory evaluation, except for SM-20 salamis which were less favoured. PMID- 22061678 TI - Review: The evolving placenta: different developmental paths to a hemochorial relationship. AB - The way in which maternal blood is associated with trophoblast prior to the formation of the different types of hemochorial placenta may be conveniently grouped into four main patterns: a transitory endotheliochorial condition; maternal blood released into a mass of trophoblast; maternal blood confined to lacunae; and fetal villi entering preexisting maternal blood sinuses. Although it might be considered logical that developing placentas would pass through an endotheliochorial stage to become hemochorial, this developmental pattern is seen only as a transient stage in several species of bats and sciuromorph rodents. More commonly a mass of trophoblast at the junction with the endometrium serves as a meshwork through which maternal blood passes, with subsequent organization of a labyrinth when the fetal vascular component is organized. The initial trophoblast meshwork may be cellular or syncytial, often leading to a similar relationship in the spongy zone and labyrinth. Old World monkeys, apes and humans have a lacunar stage prior to establishing a villous hemochorial condition. New World monkeys lack a true lacunar stage, retaining portions of maternal vessels for some time and initially forming a trabecular arrangement similar to though differently arrived at than that in the tarsier. In armadillos, preexisting maternal venous sinuses are converted into an intervillous blood space by intruding fetal villi. Variations from the major patterns of development also occur. The way in which the definitive placental form is achieved developmentally should be considered when using placental structure to extrapolate evolution of placentation. PMID- 22061679 TI - High-profile CPR: embrace the superiority of mechanical resuscitation. PMID- 22061680 TI - No comment: silence may be your worst enemy with the media. PMID- 22061681 TI - Bring a sling: humble Hoyer deserves an EMS look. PMID- 22061682 TI - Mechanical matters: consistent chest compressions help save patient. PMID- 22061683 TI - Most dangerous job: study raises awareness about the many hazards of EMS. PMID- 22061684 TI - International exchange: virtual association creates worldwide forum for EMS dialogue. PMID- 22061685 TI - Distinguishing diabetes: differentiate between type 1 & type 2 DM. PMID- 22061686 TI - Carbamazepine potentiates morphine analgesia on postoperative pain in morphine dependent rats. AB - Postoperative pain and its control remain one of the most important issues in the field of surgery and health care systems. Morphine is a potent and effective analgesic, but substance abuse patients can manifest cross-tolerance to it, making it difficult to satisfy their analgesic/anesthetic requirements. As carbamazepine has shown antinociceptive properties in a variety of experimental and clinical settings, in the present study, we evaluated its potential antiallodynic effects on postoperative pain in naive and morphine-dependent rats. Male rats were assigned to morphine-dependent and naive groups and received intraperitoneally drug vehicles as control group, 3mg/kg morphine, 5, 10 or 15 mg/kg carbamazepine or 5mg/kg carbamazepine plus 3mg/kg morphine as a combination therapy 2 and 24h after surgery. Morphine-dependency was induced with multiple doses of morphine administered i.p. and plantar incision was made on the hind paw to simulate the postoperative pain. Paw withdrawal threshold (PWT) was obtained by von Frey filaments every 30 min after drug injection for up to 180 min. Morphine at 3mg/kg exerted antiallodynic effects in naive rats and a decreased antinociception was observed in morphine-dependent rats. In contrast, 5mg/kg carbamazepine did not significantly alter PWT in naives but it was effective in dependent rats. 10 and 15 mg/kg carbamazepine attenuated allodynia following surgery in both groups. Co-administration of 5mg/kg carbamazepine with 3mg/kg morphine produced higher analgesia in morphine-dependent incised rats and prolonged antinociception as compared to morphine alone (P<0.05). Thus carbamazepine may potentiate the analgesic effect of chronically administered morphine on postoperative pain model in morphine-dependent rats. PMID- 22061687 TI - The antinociceptive effect of intrathecal escin in the rat formalin test. AB - This study investigated the antinociceptive effect of intrathecal escin and examined its effect on the formalin-induced activation of c-Fos and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) in the rat spinal cord. Rats were chronically implanted with lumbar intrathecal catheters, and the ability of intrathecal escin to alter nociceptive behaviours in the rat formalin test was examined. The expression of c-Fos and p-p38 MAPK in the dorsal horn of the spinal cord was detected in the control and escin (40MUg) groups using immunohistochemical techniques. Intrathecal escin produced a dose-dependent reduction in formalin-evoked flinching behaviour in rats during the second phase; however, no effect was observed in the first phase. In addition, immunohistochemical experiments showed that the expression of c-Fos and p-p38 MAPK in the spinal cord dorsal horn increased after an injection of formalin into the paw. Interestingly, the 40MUg dose of intrathecal escin, which was the larger of the two doses that blocked formalin-induced hyperalgaesia, attenuated the formalin-induced increases in c-Fos and p-p38 MAPK in the dorsal horn of the spinal cord. The decrease in pain-related behaviours and c-Fos expression indicated that escin produced antinociceptive effects in the rat formalin test. Although the specific mechanisms of these effects were not investigated, the reduction in p-p38 MAPK in the dorsal horn of the spinal cord may be involved. PMID- 22061688 TI - From origami to software development: a review of studies on judgment-based predictions of performance time. AB - This article provides an integrative review of the literature on judgment-based predictions of performance time, often described as task duration predictions in psychology and as expert-based effort estimation in engineering and management science. We summarize results on the characteristics of performance time predictions, processes and strategies, the influence of task characteristics and contextual factors, and the relations between estimates and characteristics of the estimator. Although dependent on the type of study and the level of analysis, underestimation was more frequently reported than overestimation in studies from the engineering and management literature. However, this was not the case in studies from the psychology literature. Our summaries challenge earlier results regarding the effects of factors such as complexity/difficulty and experience. We also question the recurrent finding that small tasks are overestimated and large tasks are underestimated, as this to some extent can be a statistical artifact caused by random error. Several other influences on predictions are identified and discussed. These include various types of anchoring effects, performance and accuracy incentives, task decomposition, request formats, group estimation, revisions of initial ideal or incomplete estimates, level of abstraction, and superficial cues. We summarize similarities and differences between performance time predictions (e.g., number of work hours) and completion time predictions (e.g., delivery dates) because many studies fail to distinguish between these 2 types of predictions. Finally, we discuss methodological issues in time prediction research and implications for research and application. PMID- 22061689 TI - The own-age bias in face recognition: a meta-analytic and theoretical review. AB - A large number of studies have examined the finding that recognition memory for faces of one's own age group is often superior to memory for faces of another age group. We examined this own-age bias (OAB) in the meta-analyses reported. These data showed that hits were reliably greater for same-age relative to other-age faces (g = 0.23) and that false alarms were reliably less likely for same-age compared with other-age faces (g = -0.23). Further meta-analyses of measures of signal detection demonstrated that, although no difference in response criterion was evident (g = -0.01), discriminability was reliably better for same-age compared with other-age faces (g = 0.37). As well, children, younger adults, and older adults exhibited superior discriminability for same-age compared with other age age faces. Thus, the OAB appears to be a robust effect that influences the accuracy of face recognition. Theoretical accounts of the OAB have generally suggested that it reflects more extensive, recent experiences with one's own age group relative to other-age groups. Additional analyses were supportive of this account as the OAB was present even for groups (e.g., older adults) that had prior experiences as members of another age group. However, the most comprehensive account of the OAB will also likely invoke mechanisms suggested by social-cognitive theories. PMID- 22061690 TI - Dyadic interracial interactions: a meta-analysis. AB - This meta-analysis examined over 40 years of research on interracial interactions by exploring 4 types of outcomes: explicit attitudes toward interaction partners, participants' self-reports of their own emotional state, nonverbal or observed behavior, and objective measures of performance. Data were collected from 108 samples (N = 12,463) comparing dyadic interracial and same-race interactions, predominantly featuring Black and White Americans. Effect sizes were small: Participants in same-race dyads tended to express marginally more positive attitudes about their partners (r = .07), reported feeling less negative affect (r = .10), showed more friendly nonverbal behavior (r = .09), and scored higher on performance measures (r = .07) than those in interracial dyads. Effect sizes also showed substantial heterogeneity, and further analyses indicated that intersectional, contextual, and relational factors moderated these outcomes. For example, when members of a dyad were the same sex, differences between interracial and same-race dyads in negative affect were reduced. Structured interactions led to more egalitarian performance outcomes than did free-form interactions, but the effects of interaction structure on nonverbal behavior depended on participant gender. Furthermore, benefits of intergroup contact were apparent: Differences in emotional state across dyadic racial composition disappeared in longer term interactions, and racial minorities, who often have greater experience with intergroup contact, experienced less negative affect in interracial interactions than did majority group members. Finally, there was a significant historical trend toward more egalitarian outcomes across dyadic racial composition for explicit attitudes and for nonverbal behavior; however, participants' emotional responses and performance have remained consistent. PMID- 22061691 TI - Integrating the study of conformity and culture in humans and nonhuman animals. AB - Conformity--defined here by the fact that an individual displays a particular behavior because it is the most frequent the individual witnessed in others--has long been recognized by social psychologists as one of the main categories of social influence. Surprisingly, it is only recently that conformity has become an active topic in animal and comparative biology. As in any new and rapidly growing field, however, definitions, hypotheses, and protocols are diverse, not easy to organize in a coherent way, and sometimes seriously in conflict with one another. Here we pursue greater coherence by reviewing the newer literature on conformity in behavioral ecology and evolutionary biology in light of the foundational work in social psychology. We suggest that the knowledge accumulated in social psychology can be exploited by behavioral ecologists and evolutionary biologists to bring conceptual clarity to the field, avoid some experimental pitfalls, and help design new and challenging experiments. In particular, we propose that the notions of informational and normative conformity that, until now, have been little recognized in recent literature can resolve some important controversies. In turn, research on animal culture should be of great interest to social scientists, because understanding human culture and human uniqueness requires an evolutionary analysis of our cognitive capacities and their evolutionary origins. Our review suggests excellent opportunities for social and natural scientists to join forces in building an interdisciplinary and integrative approach to the pervasive phenomenon of conformity. PMID- 22061692 TI - On the adequacy of current empirical evaluations of formal models of categorization. AB - Categorization is one of the fundamental building blocks of cognition, and the study of categorization is notable for the extent to which formal modeling has been a central and influential component of research. However, the field has seen a proliferation of noncomplementary models with little consensus on the relative adequacy of these accounts. Progress in assessing the relative adequacy of formal categorization models has, to date, been limited because (a) formal model comparisons are narrow in the number of models and phenomena considered and (b) models do not often clearly define their explanatory scope. Progress is further hampered by the practice of fitting models with arbitrarily variable parameters to each data set independently. Reviewing examples of good practice in the literature, we conclude that model comparisons are most fruitful when relative adequacy is assessed by comparing well-defined models on the basis of the number and proportion of irreversible, ordinal, penetrable successes (principles of minimal flexibility, breadth, good-enough precision, maximal simplicity, and psychological focus). PMID- 22061693 TI - Effect of fat level and storage conditions on quality characteristics of traditional Greek sausages. AB - Traditionally-processed Greek sausages were produced with three different fat levels (10, 20 and 30% fat). Some sausages were air dried (23-28 degrees C, 64 76% RH) for 2h and stored at 3-7 degrees C and 65-75% RH. The rest were immediately stored in a ripening room at 13-15 degrees C, 85-95% RH and 0.1m(-1)s air velocity. Fat level affected the composition of the sausages, their weight loss, brine concentration, water activity, colour and sensory attributes. Sausages with 20% fat had the highest scores for all sensory attributes. Sausages with 30% fat were very light, yellow, soft and too fatty when grilled, whereas those with 10% fat were dark and very hard after grilling. Storage conditions affected the microflora, pH, weight losses and water activity, but had no effect on composition, colour and sensory attributes. Sausages stored in the ripening room had a rapid increase in lactic acid bacteria count and lower pH than those in cold storage. Storage of traditional sausages for up to 7 days in a ripening room, similar to that used for fermented sausages, is considered beneficial. (c) PMID- 22061694 TI - Considerations of critical microorganisms and indicator enzymes in connection with the pasteurization of meat products. AB - The first part of the work gives a general survey on critical microorganisms with regard to the pasteurization of meat products. Comparison of heat resistance of two microorganisms, under isothermal conditions, is not problematic when both survivor curves follow first-order or nth order inactivation kinetics provided that reaction orders are the same. If not so or, when survivor curves follow different types of inactivation kinetics, a more complex situation arises. It is obvious that, when z-values of the microrganisms to be compared differ considerably, z(A)?z(B), the order of size of their heat resistance may be temperature dependent. The equivalent pasteurization time (EPT) is analogous with the sterilizing (F) value, but the chosen reference temperature is below 100 degrees C. In the present work, z and D values of various non-sporeforming microorganisms were collected from the literature, 12D values were calculated for 60, 70 (=T(ref)) and 80 degrees C and compared with those of 'Str. faecalis-D' selected for basis of comparison. Results demonstrated that, depending on temperature, Lb. viridescens, Moraxella-Acinetobacter and some members of Lancefield D group of streptococci appear somewhat more heat resistant than 'Str. faecalis-D'. Problems of applicability of the acid phosphatase in meat as a potential indicator enzyme when its z-value is not identical with the z value of the critical ('target') microorganism, are also discussed. The EPT value of the entire heat processing curve, measured in the centre of the product, was calculated by the well known Bigelow's 'general method' and the above-mentioned considerations were extended to non-isothermal heating conditions. PMID- 22061695 TI - Lipolytic and oxidative changes in two Spanish pork loin products: dry-cured loin and pickled-cured loin. AB - Lipolytic and oxidative changes were studied in two typical meat products from pork loin, dry-cured loin (DCL) and pickled-cured loin (PCL). Neither product registered changes in the percentages of the main lipid fractions: non polar lipids, phospholipids and cholesterol. However, in dry cured loin an important decrease was recorded in the main phospholipid classes, phosphatidyl choline and phosphatidyl ethanolamine. Muscle lipolytic enzymes were active in both products, and were accompanied by a significant increase in free fatty acids, from 0.580% (of total lipid) in fresh loin to 5.65 in DCL and 2.95% in PCL. With respect to oxidative changes, the peroxide value decreased in both products, and the TBA number only increased in PCL. PMID- 22061696 TI - Changes in intramuscular lipids during ripening of Iberian dry-cured ham. AB - Thirty-one thighs were obtained from Iberian pigs fattened with acorns and were processed during 22 months in the traditional dry-curing process. Lipolysis affecting intramuscular fat during the processing of Iberian dry-cured ham has been analyzed by studying the changes of glycerides, phospholipids and free fatty acids in lipids from Biceps femoris muscle. Little change affected the fatty acid composition of glycerides during processing. A double-phased increase in the acidity values and a decrease in the quantity of fatty acids of phospholipids during the processing were observed. There seems to be a relationship between the extension of the lipolysis taking place during the maturing and the processing conditions and raw material used. PMID- 22061697 TI - The influence of a period of ageing on the relationship between ultimate pH and shear values of beef m. longissimus thoracis. AB - Previous studies have shown that, provided cold-shortening conditions are avoided, increases in ultimate pH from a normal of about 5.5 for beef M. longissimus thoracis (LT) are associated with increased cooked meat shear forces to an intermediate pHu of about 6 and then decreases in shear force with further increases to 7. The current study with LT samples from 156 cattle (40 steers, 116 bulls) investigated this relationship following 1 and 20 days ageing at 1-2 degrees C. The patterns of change in shear values with increasing pHu were similar for both ageing times with a peak at just under 6, but the difference between 20 and 1 day samples (1-20 days) varied so that the relationship between pHu and this difference also showed a peak at intermediate pHu values. In contrast to some previous studies, sarcomere length did not decrease as pHu increased from 5.5 to 6, indicating that it is not necessarily an important determinant of toughening over this pHu range. A myofibrillar fragmentation index (MFI) increased from 1 to 20 day ageing, but the extent of the change was similar as pHu increased from 5.5 to 6.2. Over the wider range in pHu from 5.5 to 7 MFI at 1 day remained essentially constant while that at 20 days, and consequently the increase from 1 to 20 days, increased. These results do not provide evidence that any one factor is responsible for the greater toughness of beef with an intermediate pH, and suggest that factors other than degree of muscle fibre contraction and extent of myofibrillar protein breakdown may be involved. PMID- 22061698 TI - A quick and simple method for the identification of meat species and meat products by PCR assay. AB - The polymerase chain reaction (PCR) was applied to identify six meats (cattle, pig, chicken, sheep, goat and horse) as raw materials for products. By mixing seven primers in appropriate ratios, species-specific DNA fragments could be identified by only one multiplex PCR. A forward primer was designed on a conserved DNA sequence in the mitochondrial cytochrome b gene, and reverse primers on species-specific DNA sequences for each species. PCR primers were designed to give different length fragments from the six meats. The products showed species-specific DNA fragments of 157, 227, 274, 331, 398 and 439 bp from goat, chicken, cattle, sheep, pig and horse meats, respectively. Identification is possible by electrophoresis of PCR products. Cattle, pig, chicken, sheep and goat fragments were amplified from cooked meat heated at 100 or 120 degrees C for 30 min, but horse DNA fragments could not be detected from the 120 degrees C sample. Detection limits of the DNA samples were 0.25 ng for all meats. PMID- 22061699 TI - The effect of proteasome on myofibrillar structures in bovine skeletal muscle. AB - When bovine myofibrils are incubated with the 20S proteasome their structure is rapidly damaged with loss of material, particularly from the Z discs and I bands. After 24 hr of incubation the myofibrils rupture and debris appears. Certain myofibrillar proteins, including nebulin, myosin, actin and tropomyosin, are hydrolysed during the incubation; others are solubilised (alpha-actinin). The 20S proteasome completely and rapidly hydrolyses purified myofibrillar proteins in an energy-independent manner. This shows that the 20S proteasome probably plays a role in the postmortem transformation of muscle and more generally in the hydrolysis of cellular proteins.(1). PMID- 22061700 TI - Metmyoglobin reductase activity in porcine m. longissimus dorsi muscle. AB - Reduction of metmyoglobin by metmyoglobin reductase extracted from porcine m. longissimus dorsi was found to depend on the presence of NADH and to a lesser degree on the presence of an electron transfer mediator (ferrocyanide). The porcine metmyoglobin reductase was found to reduce equine metmyoglobin and metmyoglobin isolated from pigs hearts using a method described for bovine metmyoglobin. A linear increase in the rate of reduction as a function of amount of enzyme extract was observed, while the rate as a function of NADH concentration increased to a saturation level. In the pH range 6.0-7.1, the rate of reduction of porcine metmyoglobin by porcine metmyoglobin reductase increased at decreasing assay pH, apparently approaching a maximal rate around pH 6. From the temperature dependence of the maximal rate of the enzyme catalyzed reduction of porcine metmyoglobin an apparent activation energy of 33 kJ mol(-1) was calculated. Porcine metmyoglobin was also reduced by NADH in a non-enzymatic reaction, with a rather similar activation energy showing (i) that porcine metmyoglobin is more closely associated with the reductase complex than bovine metmyoglobin and not so easily separated, or (ii) that porcine metmyoglobin reduction is more facile as a non-enzymatic reaction and less dependent on electron transfer mediators compared to bovine metmyoglobin reduction. PMID- 22061701 TI - Effect of initial mild curing, with additives, of hog and sheep sausage casings on their microbial quality and mechanical properties after storage at difference temperatures. AB - Sausage containers, derived from animal intestines, are usually preserved by salting and/or drying. Adequately salted final products are microbiologically fully acceptable. However casings, even those packed in dry salt, sometimes deteriorate in quality. Experiments were performed to improve salting procedures by adding food-grade additives to the salt to improve the microbiological and mechanical properties of the casings. Before storage, casings were cured by slush or dry-salting with or without additives for 3 weeks, and after that the rinsed and re-salted (dry- or slush-salting) casings were stored for 6 months at different temperatures (10, 20, and 40 degrees C). During storage, growth of halophylic bacteria was observed in control casings (salted, no additives) but not in casings cured with citric or lactic acid and their relative sodium salts. The casings cured with citric acid/Na(3)-citrate had good mechanical properties and filling characteristics when assessed after prolonged storage at 10 degrees C. PMID- 22061702 TI - Volatile compounds of commercial Milano salami. AB - The relationship between extracted volatiles of Milano salami, one of the main dry-cured sausages produced in Italy, and their olfactory properties was studied. Volatile compounds were extracted by a purge-and-trap method, quantified using a flame ionisation detector and identified by mass spectrometry. Olfactory analysis was performed by sniffing the gas chromatographic effluent. Nearly 80 compounds were identified and quantified: most came from spices (60.5%), 18.9% from lipid oxidation, 11.8% from amino acid catabolism and 4.9% from fermentation processes. Panellists detected 19 odours by sniffing. These odours were associated with spices, lipid oxidation or fermentation and were in agreement with the contributions of each reaction to the overall aroma of the product. PMID- 22061703 TI - Effects of the terminal sire type and sex on pork muscle cathepsins (B, B+L and H), cysteine proteinase inhibitors and lipolytic enzyme activities. AB - Pork muscle cathepsins (B, B+L, and H), cysteine proteinase inhibitors and lipolytic enzyme activities were measured in the offspring of five different genetic sire types: Danish Duroc (DU), Dutch Large White (LW(D)), English Large White (LW(E)), Belgian Landrace * Landrace (BL*LR) and Belgian Landrace (BL). Cathepsin B and B+L activities were higher for LW(E) and LW(D) sires than for BL*LR and BL. Cathepsin H activity showed an opposite evolution, being higher for BL and BL*LR sires than for DU, LW(D) and LW(E). Cysteine proteinase inhibitor activity was higher for LW(E) sires than for DU and BL. In lipolytic enzymes, BL sires had a lower acid lipase activity than DU and LW(E) sires and also a lower neutral esterase activity than LW(E) and LW(D) sires. Significant differences between sexes were found for cathepsin H activity only, being higher for females. PMID- 22061704 TI - Procedure for determination of glycolytic potential in porcine m. longissimus dorsi. AB - The aim of this work was primarily to work out a procedure for removal of samples from LD for determination of glycolytic potential in connection with experiments at commercial abattoirs and secondly to determine the correlation between glycolytic potential and ultimate-pH in Danish pigs. Samples of LD were taken immediately after exsanguination and 30 h post mortem. All samples were analysed for the content of glycogen, glucose, glucose-6-phosphate and lactate to be able to calculate the glycolytic potential. The results showed no difference in glycolytic potential in LD irrespective of sampling time. Samples removed after exsanguination contained a higher amount of glycogen and less lactate than samples removed the day after slaughter, where most of the glycogen had been transformed into lactate. These results show that samples for determination of glycolytic potential in LD can be removed the day after slaughter in the chilling room instead of being removed immediately after sticking at the slaughter line, which is less practical and hygienic. There was a significant correlation (-0.61) between glycolytic potential in LD and ultimate pH in LD. PMID- 22061705 TI - Classification of tough and tender beef by image texture analysis. AB - Texture features of fresh-beef images were extracted and used to classify steaks into tough and tender groups in terms of cooked-beef tenderness. Crossbred steers varying in quality were processed in a commercial plant and two short loin steaks were sampled from each carcass. One sample was used for imaging and the other was broiled for sensory evaluation of tenderness by a trained panel. The samples were segregated into tough and tender groups according to the sensory scores. A wavelet-based decomposition method was used to extract texture features of fresh beef images. The texture feature data for 90 sample images were used to train and test sample calssifiers in a rotational leave-one-out scheme. A correct classification rate of 83.3% was obtained in cross validations. While texture features alone may not be sufficient to segregate beef products into many levels of tenderness, they can be significant members in a set of indicators that will lead to adequate tenderness prediction. PMID- 22061706 TI - Tenderization of beef by lactic acid injected at different times post mortem. AB - The potential to tenderize beef muscles by the injection of lactic acid (0.5 M, 10% w/w) was studied using the pectoralis profundus muscle from cull cows. The injection was performed either 1 h (pre rigor) or 24 h (post rigor) post mortem, and the meat was stored for 2 or 14 days post mortem. Both treatments caused a rapid pH drop to around 5.0 within 4 h of injection. Other effects were: (1) an accelerated release of lysosomal enzymes into the cytosol; (2) a greater degradation of myosin heavy chains; (3) ultrastructural alterations of the myofibrils which included a general weakening or rupture in the M-lines and, to a lesser extent, in the I-bands; (4) a decreased heat stability of perimysial collagen indicated by a lower insoluble collagen content, lower differential scanning calorimetry transition temperature, and lower transition temperatures in isometric tension tests on muscle strips. The lactic acid injections improved significantly the textural traits of the meat (shear value, tensile strength, sensory scores) at 2 days post mortem with little further improvement when storage was extended to 14 days post mortem. Changes in texture were of similar amplitude at both post mortem injection times. The tenderization mechanisms of lactic acid injection are discussed. PMID- 22061707 TI - Consumer preferences for beef color and packaging did not affect eating satisfaction. AB - We investigated whether consumer preferences for beef colors (red, purple, and brown) or for beef packaging systems (modified atmosphere, MAP; vacuum skin pack, VSP; or overwrap with polyvinyl chloride, PVC) influenced taste scores of beef steaks and patties. To test beef color effects, boneless beef top loin steaks (choice) and ground beef patties (20% fat) were packaged in different atmospheres to promote development of red, purple, and brown color. To test effects of package type, steaks and patties were pre-treated with carbon monoxide in MAP to promote development of red color, and some meat was repackaged using VSP or PVC overwrap. The differently colored and packaged meats were separately displayed for members of four consumer panels who evaluated appearance and indicated their likelihood to purchase similar meat. Next, the panelists tasted meat samples from what they had been told were the packaging treatments just observed. However, the meat samples actually served were from a single untreated steak or patty. Thus, any difference in taste scores should reflect expectations established during the visual evaluation. The same ballot and sample coding were used for both the visual and taste evaluations. Color and packaging influenced (P<0.001) appearance scores and likelihood to purchase. Appearance scores were rated red>purple >brown and PVC >VSP>MAP. Appearance scores and likelihood to purchase were correlated (r=0.9). However, color or packaging did not affect (P>0.5) taste scores. Thus, consumer preferences for beef color and packaging influenced likelihood to purchase, but did not bias eating satisfaction. PMID- 22061708 TI - Composition assessment of raw meat mixtures using ultrasonics. AB - The use of ultrasonic velocity measurements to determine the composition of dry fermented sausages was assessed. Mixtures of ground lean and fatty tissues were prepared to cover a wide range of fat (2-90 wt.%), moisture (7-76 wt.%), and protein (2-21 wt.%) contents. The ultrasonic velocity in fat decreased on average 5.6 ms(-1) per degrees C increase in temperature, due to the negative temperature coefficient for fat and the fat melting, which is observed in (DSC) differential scanning calorimetry analysis. The ultrasonic velocity temperature dependence allowed the determining of the fat, moisture and protein+others content, by measuring the ultrasonic velocity in the mixtures at 4 and 25 degrees C and using a semi-empirical equation. The explained variance was 99.6% for fat, 98.7% for moisture and 85.4% for protein+others. The results obtained show the feasibility of using ultrasonic velocity measurement to assess the composition of meat products such as dry fermented sausages, rapidly and non-destructively. PMID- 22061709 TI - n-Alkane content of intramuscular lipids of Iberian fresh ham from different feeding systems and crossbreeding. AB - n-Alkane content of intramuscular lipids (Biceps femoris muscle) of the Iberian pig have been determined. Thirty-four pigs, divided into four groups, based in the feeding system (Montanera, fed on acorns and pasture; and Pienso, fed on a concentrate feed) and in the genotype (Iberian pure pigs; and Iberian crossbred with Duroc 50%) were studied. n-Alkane content of intramuscular lipids has not been affected by neither crossbreeding nor feeding, although the analysis of feeds administered to the pigs showed greater n-alkane values in pasture (consumed by animals in montanera), than in acorns and concentrate feed. PMID- 22061710 TI - The eating quality of meat of steers fed grass and/or concentrates. AB - The objective was to determine, relative to animals expressing their full potential for carcass growth, the impact on meat quality of increasing carcass growth of grazing steers by supplementing with concentrates or by increasing grass supply. Sixty-six continental (Limousin and Charolais) crossbred steers (567 kg) were assigned to one of six diets: (1) 18 kg grass dry matter (DM); (2) 18 kg grass DM grass and 2.5 kg concentrate; (3) 18 kg grass DM and 5 kg concentrate; (4) 6 kg grass DM and 5 kg concentrate; (5) 12 kg grass DM and 2.5 kg concentrate; or (6) concentrates daily. Animals were slaughtered after an average of 95 days. Samples of the M. longissmus dorsi (LD) were collected at the 8-9th rib interface and subjected to sensory analysis and to other assessments of quality following 2, 7, or 14 days aging. Carcass weight gain averaged 360, 631, 727, 617, 551 and 809 g/day for treatments 1 to 6, respectively. There was no difference between diets for colour, Warner-Bratzler shear force (WBSF) or any sensory attribute of the LD. WBSF was negatively correlated with (P<0.05) carcass growth rate (-0.31) but only a small proportion of the variation in meat quality between animals could be attributed to diet pre-slaughter or carcass fatness. It is concluded that high carcass growth can be achieved on a grass-based diet without a deleterious effect on meat quality. PMID- 22061711 TI - Inulin as fat substitute in low fat, dry fermented sausages. AB - Low fat, dry fermented sausages were prepared with a fat content close to 50% and 25% of the original amount. The batch with the smallest proportion of fat was less tender, less springy and was gummier than the batch with the highest proportion. However, it was still considered acceptable by the panel of judges. The 25% batch was supplemented with different amounts of soluble dietetic fibre (inulin) as both a powder and in aqueous solution. Ripening was followed by physico-chemical and microbiological analysis. Sensory analysis and texture profile analysis were performed to evaluate the effect of the inulin addition. Results obtained indicated an overall improvement in the sensory properties due to a softer texture and tenderness, springiness and adhesiveness similar to the conventional high fat sausage. Thus, with the addition of inulin a low calorie product (30% of the original), enriched with soluble dietetic fibre (10% approximatively) can be obtained. PMID- 22061712 TI - Evolution of hydrophobic polypeptides during the ageing of exudative and non exudative pork meat. AB - Thirty-six carcasses from 6-month-old pigs were classified in different exudative groups based on measurements of pH(2h), pH(24h), the colour parameter L(*) and drip loss. A fraction containing polypeptides between 66 and 21 kDa was analysed by reverse phase chromatography at 2-h post-mortem and the evolution of 8 polypeptide fractions followed during ageing and related to meat quality. Three polypeptide (fractions P2, P3 and P4) at 2-h post-mortem showed significant lowest area values in the dark firm and dry class. During ageing, the higher content of P4 in exudative meats at 8-h post-mortem could be due to activation of the cathepsin system. On the other hand, P3 and P4 increased in DFD meats during the first 96-h post-mortem probably due to higher calpain activity. Few differences in polypeptides were related to meat qualities although they are important as precursors of small peptides and free amino acids. PMID- 22061713 TI - Blast chilling and low voltage electrical stimulation influences on bison (Bison bison bison) meat quality. AB - Conventional carcass chilling is a lengthy and energy expensive process. Blast chilling (BL) can reduce cooling time and associated shrink loss, although its application may compromise meat quality, particularly in lean carcasses or those with localized finish such as bison. Low voltage electrical stimulation (LVES) can reduce the risk of decreased meat quality by inducing rapid rigor onset prior to exposure of the musculature to extreme cold temperature. BL (-20 degrees C, 3 m.s(-1) air velocity, 2 h) accelerated temperature decline of bison Longissimus lumborum (LL) and significantly reduced cooler shrink loss versus conventional chilling (CONV: 0-2 degrees C, 24 h). While BL tended to produce darker meat, this effect was tempered by the application of LVES, and samples from the combined treatment were significantly lighter than CONV. BL resulted in reduced tenderness in the LL, as assessed by shear force measurement, in part due to significantly shorter sarcomere length in BL samples. Taste panelists, however, were unable to detect a significant or detrimental BL effect. Where LVES was incorporated, there was an improved tenderness response with ageing. The combined LVES/BL treatment of bison carcasses is recommended for rapid processing without compromising meat quality. PMID- 22061714 TI - Effect of irradiation and packaging conditions after cooking on the formation of cholesterol and lipid oxidation products in meats during storage. AB - The effect of irradiation and packaging conditions on the content of cholesterol oxidation products (COPs) and lipid oxidation in cooked turkey, beef, and pork during storage was studied. Ground turkey leg, beef, and pork were cooked, packaged either in oxygen-permeable or oxygen-impermeable bags, and irradiated at 0 or 4.5 kGy. Lipid oxidation and COPs were determined after 0 and 7 days of storage at 4 degrees C. Packaging of cooked meat was more important than irradiation in developing COPs and lipid oxidation in cooked meats during storage. 7alpha-Hydroxycholesterol, 7beta-hydroxycholesterol, beta-epoxide, and 7 ketocholesterol were among the major COPs formed in cooked turkey, beef, and pork after storage, and their amounts increased dramatically during the 7-day storage in aerobic conditions. Irradiation had no significant effect on the amounts of any of the COPs found in cooked turkey and beef, but increased (P<0.05) the amounts of alpha- plus 7beta-hydroxycholesterol, beta-epoxide, 7-ketocholesterol, and total COPs in aerobically packaged cooked pork. The amounts of COPs and lipid oxidation products (TBARS) closely related to the proportion of polyunsaturated fatty acids in meat. The results indicated that the composition of fats in meat is important on the oxidation rates of lipids and cholesterol, and packaging is far more important than irradiation in the formation of COPs and lipid oxidation in cooked meat. PMID- 22061715 TI - Volatile production in irradiated normal, pale soft exudative (PSE) and dark firm dry (DFD) pork under different packaging and storage conditions. AB - Normal, pale soft exudative (PSE) and dark firm dry (DFD) pork Longissimus dorsi muscles were vacuum packaged, irradiated at 0 or 4.5 kGy and stored at 4 degrees C for 10 days. Volatile production from pork loins was determined at Day 0 and Day 10 of storage at 4 degrees C. With both aerobic and vacuum packaging, irradiation increased the production of sulfur-containing volatiles (carbon disulfide, mercaptomethane, dimethyl sulfide, methyl thioacetate and dimethyl disulfide) in all three pork conditions at Day 0 but did not increase hexanal - the major indicator volatile of lipid oxidation. The PSE pork produced the lowest amount of total sulfur-containing volatiles in both aerobically and vacuum packaged pork at Day 0. The majority of sulfur-containing volatiles produced in meat by irradiation disappeared during the 10-day storage period under aerobic packaging conditions. With vacuum packaging, however, all the volatiles produced by irradiation remained in the packaging bag during storage. Irradiation had no relationship with lipid oxidation-related volatiles (e.g. hexanal) in both aerobic and vacuum-packaged raw pork. The DFD muscle was very stable and resistant to oxidative changes in both irradiated and nonirradiated pork during storage, suggesting that irradiation can significantly increase the utilization of raw DFD pork and greatly benefit the pork industry. PMID- 22061716 TI - Metmyoglobin reducing activity and colour stability of ovine longissimus muscle. AB - Characteristics of metmyoglobin reducing activity in ovine longissimus were determined, and its effect on colour and colour stability of muscle was investigated in two experiments. In the first experiment vacuum packed ovine longissimus samples were incubated at 5-35 degrees C during the first 16 h post mortem (n=8 per treatment). Metmyoglobin reducing activity was negatively affected by incubation temperatures above 30 degrees C, but colour and colour stability were little affected at 24 h post mortem and after 2 weeks of vacuum storage at 2 degrees C. In the second experiment the effects of pre-slaughter stress and electrical stimulation on metmyoglobin reducing activity, colour and colour stability of ovine longissimus (n=40) with an ultimate pH below 5.8 were investigated. Neither of the treatments had an effect on metmyoglobin reducing activity or colour parameters. The relatively large variation in metmyoglobin activity and colour parameters allowed correlation analysis. Metmyoglobin reducing activity was not correlated to colour or the colour stability parameters. The results of the present study indicate that metmyoglobin reducing activity is not the primary determinant of colour or colour stability of ovine longissimus muscle. PMID- 22061717 TI - Soy protein isolate added to vacuum-packaged chorizos: effect on drip loss, quality characteristics and stability during refrigerated storage. AB - Chorizo is a raw sausage, which is manufactured with beef, pork meat and pork fat, additives and spices. In Argentina, the expenditure of chorizo is through butchery and supermarkets where the product can be found packaged in both polyethylene films and vacuum sealed pouches. In the latter type of packaging an appearance problem has been detected in relation to drip loss. The aim of the work was to solve such problem through the incorporation of soy protein isolate (SPI). The sensory, microbiological and chemical stability of the product and its drip loss during a storage period of 14 days were studied. By adding a 2.5% SPI, the drip loss was prevented without introducing any change in the flavour, aroma and juiciness characteristics of the product. These sensory attributes were kept stable during the storage period studied. Chemical composition, oxidative and microbiological stability were not affected by the addition of SPI during the storage period, being similar for added and non-added SPI samples. Finally, SPI can be used in chorizos to improve their overall appearance during refrigerated storage while the product quality characteristics are not altered. PMID- 22061718 TI - Magnesium involvement in pain. PMID- 22061720 TI - Quality and shelf life evaluation of emulsion and restructured buffalo meat nuggets at cold storage (4+/-1 degrees C). AB - The study was aimed at comparing the physico-chemical characteristics and texture profile of emulsion and restructured buffalo meat nuggets (BMN) and assessing their shelf life at refrigeration temperature (4+/-1 degrees C). The stability of restructured batter was significantly lower than that of the emulsion form. Emulsion nuggets (EN) had significantly higher product yield, fat content and calories while restructured nuggets (RN) had significantly higher moisture and protein contents. Texture profile analysis revealed that RN had significantly higher cohesiveness, gumminess, chewiness and shear force values. Differences in TBARS values for emulsion and restructured nuggets were not significant at any particular storage time. Throughout storage, counts for mesophilic, psychrotrophic and coliforms did not exceed log(10)3.09 and 3.44cfu/g, log(10)2.23 and 2.11cfu/g, log(10)1.30 and 1.30cfu/g for emulsion and restructured buffalo meat nuggets, respectively. In spite of a higher overall acceptance for EN initially, panelists rated them considerably lower compared to RN during subsequent storage. Buffalo meat nuggets were acceptable for at least 20 days in cold storage (4+/-1 degrees C) under aerobic conditions in polypropylene bags. PMID- 22061721 TI - The effect of enhancement with salt, phosphate and milk proteins on the physical and sensory properties of pork loin. AB - Pork loins were pumped to 110% of original weight with solutions containing 5.5% salt and 3.3% sodium tripolyphosphate, 5.5% salt and 3.3% beta-lactoglobulin (beta-lg) enriched fraction or 5.5% salt and 3.3% whey protein concentrate 80% (WPC80) for comparison with non-enhanced control loins. The enhancement of pork loins significantly increased (p<0.001) the tenderness and juiciness. Warner Bratzler shear force values were lower (p<0.001) in enhanced then in non-enhanced control chops. The enhanced pork chops had a slightly higher overall flavour and overall acceptability to the control pork chops. Sensory analysis showed that beta-lg enriched fraction and WPC80 can be used as replacement ingredients to reduce the amount of phosphate used in enhancement solutions, as they were comparable to salt/sodium tripolyphosphate (salt/STPP) enhancement solution. Consumers rated the tenderness, juiciness and taste of the enhanced chops significantly (p<0.001) higher then the control chops. PMID- 22061722 TI - Optimizing palm oil and palm stearin utilization for sensory and textural properties of chicken frankfurters. AB - This study was designed to explore the potential of refined, bleached and deodorized (RBD) palm oil (PO) and palm stearin (POs) utilization in chicken frankfurters. A 10 points augmented simplex-centroid design was used to study the effect of chicken fat (CF), PO and POs as well as the interaction of these fats on the emulsion, textural and sensory properties of chicken frankfurters. All frankfurters were formulated to contain approx 25% fat, 52% moisture and 10% protein. No significant difference was found in end chopping temperatures of all meat batters even though the temperature of PO and POs upon incorporation into meat batters was 50 degrees C higher than CF. Strong emulsions were formed as no fluid losses were observed in all the meat batters tested after heating. Texture profiles of the frankfurters containing PO and/or CF were quite similar, but increment of POs raised hardness, chewiness, and shear hardness of the frankfurters. Acceptability of the frankfurters was evaluated using hedonic test. Panelists found no difference in hardness preference between frankfurters made from totally CF and PO, while frankfurters made from POs were rated as hard and brittle. CF was important in determining acceptability of the frankfurters, as reduction of CF in formulation resulted in lower scores in chicken flavor, juiciness, oiliness and overall acceptance of the frankfurters. Frankfurters with sensory acceptability comparable to a commercial one were found to comprise of more than 17% CF, and less than 67% PO and 17% POs of the fat blend. PMID- 22061723 TI - Combination of NMR and MRI quantitation of moisture and structure changes for convection cooking of fresh chicken meat. AB - This study demonstrates that a combination of bulk NMR and magnetic resonance imaging measurements of the T(2)-values of water protons can be used to determine the heat-induced changes in the structure and moisture content of fresh chicken meat which had been cooked in a convection oven at 200 degrees C for a range of times. The gravimetric moisture content was also determined for both the raw and cooked meat. Multi-exponential fitting of the bulk NMR T(2) relaxation time data demonstrated three distinct water populations T(21) (39-43ms), T(22) (82-99ms) and T(23) (2-3ms) for raw meat which changed to 18-31ms (T(21)), 61-208ms (T(22)) and 3-7ms (T(23)) after the meat had been cooked. The T(1) and T(2) values obtained by MRI for cooked meat decreased progressively with increased heating time. There are highly significant correlations between the T(2) values from MRI and the T(21) values from bulk NMR measurements of cooked meat (r=0.986; p<0.01), and also between the normalised M(0) values from MRI and the gravimetric moisture content (r=0.953; p<0.01). PMID- 22061724 TI - Enhancement with varying phosphate types, concentrations, and pump rates, without sodium chloride on beef biceps femoris quality and sensory characteristics. AB - Beef biceps femoris muscles (n=45) were used to evaluate the effect of enhancement with solutions containing sodium hexametaphosphate (SHMP), sodium tripolyphosphate (STPP), or tetrasodium pyrophosphate (TSPP) at either 0.2% or 0.4% of product weight, without sodium chloride. All solutions were injected into muscle samples at either 112% (12% pump) or 118% (18% pump) of raw product weight. Muscles enhanced with STPP or TSPP had a higher (P<0.05) pH than SHMP or untreated muscles (CNT), whereas there was no difference (P>0.05) in pH between SHMP and CNT. Muscles enhanced with STPP had less (P<0.05) free water than CNT, whereas SHMP and TSPP did not differ from CNT. However, direct comparison of phosphate types revealed no difference (P>0.05) in free water. Steaks enhanced with SHMP had greater (P<0.05) cooking losses than CNT, whereas steaks treated with STPP or TSPP did not differ (P>0.05) from CNT. Phosphate inclusion at 0.2% allowed for greater (P<0.05) cooking losses than CNT, whereas 0.4% phosphate inclusion exhibited similar (P>0.05) cooking losses as CNT. Although there were no differences (P>0.05) in cooking loss between pump rates, steaks enhanced at an 18% pump rate had greater (P<0.05) cooking losses than CNT, whereas those enhanced at 12% had similar (P>0.05) cooking losses as CNT. Enhancement with any of the three phosphate types or either concentration did not improve (P>0.05) sensory tenderness or juiciness characteristics compared to CNT, but enhancement at an 18% pump rate allowed for improved (P<0.05) overall tenderness, compared to a 12% pump rate. These results suggest that while phosphate enhancement independent of sodium chloride generally did not improve water retention, cooked yields and palatability compared to untreated samples, utilizing higher phosphate concentrations or utilizing STPP or TSPP effectively retained the additional water associated with solution enhancement, allowing for similar free water and cook yields as untreated samples. PMID- 22061725 TI - Effect of forage to concentrate ratio on growth performance, and on carcass and meat quality of Podolian young bulls. AB - The effect of forage to concentrate ratio: 60-40 [high concentrate group (HC) and 70-30 [low concentrate group (LC)] on growth, slaughtering performance and meat quality were evaluated in twenty organically farmed Podolian young bulls. Meat quality characteristics were measured on three different muscles [Longissimus dorsi (LD), Semimembranosus (SM) Semitendinosus (ST)], vacuum-packaged and chilled stored at 2-4 degrees C for 15 days. The animals in the HC group had higher weight gain than those in the LC group (P<0.05). Slaughter data were not influenced by ration composition. The higher forage to concentrate ratio produced an improvement in fatty acid composition of the three muscles, with a higher polyunsaturated to saturated ratio (P<0.001). Vitamin E and malondialdehyde (MDA) contents were not affected by the feeding treatment. Panel scores for tenderness and flavour (P<0.01) and Warner-Bratzler Shear force (P<0.001) were significantly affected by muscle, the LD muscle being the most tender and the richest in flavour but they not affected by dietary treatment. PMID- 22061726 TI - Fatty acid composition, conjugated linoleic acid isomers and cholesterol in beef from crossbred bullocks intensively produced and from Alentejana purebred bullocks reared according to Carnalentejana-PDO specifications. AB - The purpose of this study was to characterise and compare the nutritional value of Portuguese Carnalentejana-PDO beef, obtained from Alentejana purebred bullocks reared in a semi-extensive system, with the meat from Alentejana*Charolais crossbred bullocks produced in a conventional intensive concentrate-based system. In addition, seasonal changes in Carnalentejana-PDO beef quality were assessed, by analysing meat samples from animals slaughtered in early autumn and late spring. The results showed that beef-PDO has different intramuscular fat characteristics in comparison with meat from crossbred bullocks fed intensively with concentrate. However, the finishing period of Alentejana purebred bullocks with concentrate seems to attenuate most of the typical grass-fed characteristics of meat fat. Nevertheless, from a human nutrition perspective, Carnalentejana-PDO beef seems to be healthier than that from intensively reared animals since it has a lower n-6/n-3 ratio, although always above the recommended guidelines for human diet, and higher proportions of c9,t11 conjugated linoleic acid (CLA) isomer and total CLA relative to saturated fatty acids plus total cholesterol (CLA/SFA+CHR). Furthermore, no seasonal variation in the nutritional quality of beef-PDO was apparent. Taken together, the data indicate that Carnalentejana-PDO beef is of greater nutritional value than intensively produced beef from crossbred bullocks throughout the year. PMID- 22061727 TI - Identification of lactic acid bacteria isolated from kimchi and studies on their suitability for application as starter culture in the production of fermented sausages. AB - The aim of the investigation was to identify strains of lactobacilli coming from kimchi with properties suitable for use as starter cultures in sausage fermentation. A total of 31 strains of lactobacilli were isolated from kimchi on the 4-6th day of fermentation at 20 degrees C using MRS agar plates and identified on the basis of morphological, biochemical, and physiological characteristics. The isolates were identified as Leuconostoc mes.mes./dent (12.9%), Lactobacillus curvatus (9.7%), Lactobacillus brevis (35.5%), Lactobacillus sake (25.8%), and Lactobacillus plantarum (16.1%). Thus, 51.6% of the isolates were homo-fermentative or facultative hetero-fermentative bacteria and the rest (48.4%) were hetero-fermentative bacteria. Among them L. brevis, L. curvatus, L. plantarum, and L. sake were investigated for their growth profile and metabolism characteristics in the fluid (submerged) model-medium modified according to the special conditions of fermented sausages. Relatively good growth properties were found for L. brevis, L. plantarum, and L. sake with maximum numbers of 8.18, 8.51 and 8.17cfu/ml, respectively, whereas L. curvatus could not adapt to the special environmental conditions. Regarding souring properties, L. brevis showed little ability to decrease pH, whereas L. curvatus, L. plantarum, and L. sake showed relatively good acidifying properties. According to the results of glucose fermentation and its products, only L. plantarum exhibited homo-fermentative characteristics. As a result only L. plantarum among the isolates from kimchi had an ability to adapt to the complex environment of fermented sausage, which will thereby allow them to act as starter cultures and natural preservatives in sausage production. PMID- 22061728 TI - The antioxidative properties of Holy basil and Galangal in cooked ground pork. AB - The ethanolic extracts from Holy basil and Galangal were examined for their extraction yield, total phenolic content, antioxidant activity against a beta carotene-linoleic acid emulsion system, DPPH scavenging activity and reducing power. Ethanolic extracts of Holy basil exhibited higher extraction yield, total phenolic content, antioxidant activity, DPPH scavenging activity and reducing power than ethanolic extracts of Galangal. Antioxidative efficiency to inhibit lipid oxidation of dried Holy basil and dried Galangal powder, ethanolic extracts of Galangal and Holy basil and commercial antioxidant mixture in cooked ground pork was investigated during refrigerated storage at 5 degrees C for 14 days. The quantitative measurements of thiobarbituric acid reactive substances (TBARS), conjugated diene, peroxide value (POV) and hexanal content were used as indicators of lipid oxidation. Increased levels of TBARS value, POV and hexanal content were noticed in all meat samples during storage, however most marked in cooked ground pork without antioxidants, whereas conjugated diene tended to decrease with increasing storage time. Ranking of the treatment in order of their antioxidant effectiveness showed that commercial antioxidant mixture (0.3% citric acid+0.5% ascorbic acid+0.02% alpha-tocopherol)>dried Galangal powder>dried Holy basil powder>ethanolic extracts of Galangal>ethanolic extracts of Holy basil>control. Furthermore, in cooked ground pork samples a high correlation between TBARS value and hexanal contents was obtained. PMID- 22061729 TI - Sensory improvement of dry-fermented sausages by the addition of cell-free extracts from Debaryomyces hansenii and Lactobacillus sakei. AB - The effects of the addition of a combined cell-free extract from Lactobacillus sakei and Debaryomyces hansenii (D+L) or just a D. hansenii cell-free extract (D) to the initial formulation of a dry-fermented sausage were evaluated. The differences found among batches in the main microbial populations, pH, moisture content and global proteolytic and lipolytic indexes (total free amino acids, non protein nitrogen, acidity and tiobarbituric acid index) were not significant. Only, the acidity value of batch D was significantly higher (p<0.05) than that of batch D+L. Thus, cell-free extract from D. hansenii accelerated the lipolysis. Moreover, there were some significant differences (p<0.05) in the amino acid profile and, especially, in the aroma profile. The combination D+L and D promoted the generation of volatile compounds derived from lipid oxidation and carbohydrate fermentation. In batch D, the production of volatile compounds derived from amino acid catabolism and microbial fermentation was also enhanced. The overall quality was improved by both treatments (D+L, D) and also the aroma by addition of the combination of extracts (D+L). It is concluded that the addition of cell-free extracts from D. hansenii and, particularly, D. hansenii plus L. sakei could be useful to improve the final quality of fermented sausages. PMID- 22061730 TI - Radio frequency heating of beef rolls from biceps femoris muscle. AB - Chemical, physical and sensory aspects of quality were compared on encased rolls (1kg) prepared from single muscle beef (biceps femoris) cooked in a steam oven (80 degrees C) or by radio frequency (RF) heating (500W, 27.12MHz) under recirculating water at 80 degrees C. The RF protocol reduced cooking times to 23 and 31% of steam cooking times, respectively, in non-injected meat (PG1) and in rolls prepared with curing brines possessing similar dielectric properties (PG2 4). Compared to steam heating, cooking yields were significantly higher (P<0.05) and instrumental texture measurements related to toughness significantly lower (P<0.05) for RF cooked PG1 rolls and for meat injected with brines containing water binding dielectrically inactive additives (PG4) but not for brined rolls lacking the latter ingredients (PG2 and PG3). Participants in a 50 member untrained sensory panel were unable to detect texture differences which had been indicated by instrumental analysis for PG1 and PG4. PMID- 22061731 TI - Intramuscular and subcutaneous lipid fatty acid profile composition in male and female foals. AB - This study characterised the lipid classes of Longissimus dorsi (LD) muscle and the fatty acid profiles of the LD intramuscular fat and subcutaneous (SC) adipose tissue of male and female foal mixed populations. Two animal groups were studied based on slaughter ages of 16 and 24 months. The sex of the animals had no statistical significance in the lipid fractions of the LD muscle or in the intramuscular fatty acids (p?0.05). In contrast, there was a significant effect of sex on the fatty acid profile of the SC adipose tissue. Furthermore, the livestock production system showed difference in both lipid class and fatty acid profiles from the LD and SC adipose tissues. The LD of 24-month old foals had lower phospholipids content (p?0.001), displayed little difference in saturated fatty acids (SFA) (p?0.1), exhibited higher levels of monounsaturated fatty acids (MUFA) (p?0.05) and lower levels of polyunsaturated fatty acids (PUFA) (p?0.05) compared with that of the 16-month old foals. Furthermore, the fatty acid profile of the SC adipose tissue of the 24-month old foals had higher SFA (p?0.05) and PUFA (p?0.01) with lower amounts of MUFA (p?0.001) relative to the 16-month old foals. PMID- 22061732 TI - The influence of breed and mh-genotype on carcass conformation, meat physico chemical characteristics, and the fatty acid profile of muscle from yearling bulls. AB - The influence of breed and mh-genotype on carcass conformation, meat physico chemical characteristics and the fatty acid profile of muscle were studied. Samples from 16 yearling bulls from "Asturiana de los Valles" (AV, n=12) and "Asturiana de la Montana" (AM, n=4) were collected. AV animals were classified into three groups according to the presence of the gene causing double-muscling (AV double-muscled (mh/mh), n=4; AV heterozygous (mh/+), n=4; AV normal (+/+), n=4). Double-muscled animals displayed better carcass traits, lower total fat (comprised of subcutaneous (SC), intermuscular (IT) and intramuscular (IM) deposits), higher lean, moisture and drip loss, and lighter meat than AV normal animals. Heterozygous animals showed intermediate characteristics. AM animals, being a more rustic and smaller breed, showed lower conformation, higher total fat (SC, IT and IM), lower moisture and darker meat. According to the intramuscular fatty acid profile, mh/mh animals showed a lower proportion of SFA and MUFA, and a higher proportion of PUFA with an equal proportion of CLA in total fatty acid content. The P/S ratio increased with increasing number of mh alleles (or double-muscling character), while no differences between animal groups were found for the n-6/n-3 ratio. PMID- 22061733 TI - Carcass merit between and among family groups of Bos indicus crossbred steers and heifers. AB - Differences in live and carcass traits attributable to increasing Bos indicus breed influence were compared to the differences between families with similar proportions of B. indicus influence. Families of offspring from 1/2 Angus*1/2 B. indicus mated to Angus, B. indicus, and 1/2 Angus*1/2 B.indicus were raised under similar conditions. Average daily gain, slaughter weight, and dressing percentage were measured in addition to USDA yield and quality grade factors. Breed type did not affect average daily gain, slaughter weight, dressing percentage, carcass weight, adjusted 12th-rib fat thickness, estimated percentage kidney, pelvic, and heart fat, or carcass maturity. Predominately (3/4) Angus progeny produced greater (P<0.05) longissimus muscle areas than 3/4 B. indicus animals. Predominately Angus cattle also had greater (P<0.05) marbling scores and USDA quality grades than predominately B. indicus cattle. Families within breed types differed (P<0.05) with regard to all traits measured. This is interesting in light of the lack of differences between breeds for most traits. In some instances, the differences in marbling score and longissimus muscle area between families within a given breed type were similar or greater in magnitude than the differences observed between predominately Angus and predominately B. indicus breed types. Whereas growth and carcass traits varied between levels of B. indicus breeding, the opportunity does exists to improve these traits by selecting within specific family lines. PMID- 22061734 TI - Effects of enhancement with differing phosphate types, concentrations, and pump rates, without sodium chloride, on beef biceps femoris instrumental color characteristics. AB - Enhancement of beef biceps femoris muscles (n=45) with solutions comprising sodium hexametaphosphate (SHMP), sodium tripolyphosphate (STPP), or tetrasodium pyrophosphate (TSPP) at either 0.2% or 0.4% of product weight, with the exclusion of sodium chloride, was performed to observe the independent phosphate effects on instrumental color during simulated retail display. All solutions were injected into muscle samples at either 112% (12% pump) or 118% (18% pump) of raw product weight. All three phosphate types maintained higher (P<0.05) L* values than untreated steaks (CNT) through 5 days-of-display, and SHMP had higher (P<0.05) L* values than STPP and TSPP through 7 days-of-display. Additionally, steaks with 0.2% phosphate inclusion were lighter (L*; P<0.05) than CNT throughout display, and were lighter (P<0.05) than steaks enhanced with 0.4% phosphates through 7 days of display. Steaks enhanced with TSPP had higher (P<0.05) a* values than CNT on days 5 and 7 of display, whereas SHMP- or STPP-enhanced steaks generally had similar (P>0.05) a* values as CNT after 3d of display. Direct comparison of phosphate concentrations revealed no differences (P>0.05) in a* values. Only steaks enhanced with TSPP were more vivid (P<0.05) and had higher (P<0.05) proportions of oxymyoglobin than CNT on days 5 and 7 of display. However, direct comparison of phosphate types indicated that TSPP- and STPP-enhanced steaks had similar (P>0.05) oxymyoglobin proportions during display. Phosphate inclusion at 0.4% maintained higher (P<0.05) oxymyoglobin proportions than 0.2% phosphate inclusion through 5 days-of-display. These results indicate that while 0.2% phosphate concentrations maintain lighter color, 0.4% concentrations can more effectively retain oxymyoglobin during display. Additionally, only steaks enhanced with TSPP were redder, more vivid, and had higher oxymyoglobin proportions than untreated steaks during the latter stages of display. PMID- 22061735 TI - Effects of enhancement procedures on whole and re-formed beef forequarter muscles. AB - Beef Supraspinatus and Triceps brachii muscles were subjected to three enhancement and/or re-forming treatments: (i) injected whole @ 15%w/w with salt phosphate solution; (ii) injected and re-formed; (iii) injected with added flavouring and re-formed. The treated muscles were compared to whole uninjected controls. All injection treatments reduced shear force values of cooked samples and in most cases these reductions were reflected in sensory panel tenderness and chewiness ratings. For example, shear values for Supraspinatus were 83N/g in control samples and 50 in whole injected samples, while corresponding sensory panel tenderness ratings were 3.6 and 5.2. Enhanced samples did not differ from controls in sliceability or in colour and binding ratings, indicating that enhancement combined with re-forming can give an acceptable roast beef product. There were no differences in drip loss and very few differences in colour L*, a* and b* values for raw samples between any of the treatments. Addition of beef stock did not result in higher flavour ratings by sensory panels. Whole injected samples scored higher for flavour than both control (p<0.01) and injected+re formed (p<0.05) samples. PMID- 22061736 TI - Association between body composition of growing pigs determined by magnetic resonance imaging, deuterium dilution technique, and chemical analysis. AB - Development of body composition of 440 growing pigs from a three generation full sib design to identify quantitative trait loci (QTL) was determined by three different methods. Firstly, the non-invasive method deuterium dilution technique (DT), was applied to all pigs in the experiment at six weights 20, 30, 60, 90, 120 and 140kg. Secondly, at each weight class, eight pigs were slaughtered and their entire body chemically analysed (CA). Thirdly, magnetic resonance imaging (MRI) was applied on 16 live pigs at different weights. For the entire empty body (without content of the gastrointestinal tract and bladder), allometric prediction equations to predict body composition from empty body water content measured by DT were derived from chemically analysed serial slaughtered pigs. These equations showed high correlations of 0.92, 0.90 and 0.85 for the contents of body water, fat-free substance as well as protein in fat-free substance, respectively. For the soft tissue (empty body without bones and viscera), allometric prediction equation of body composition based on DT and CA showed correlations of 0.91, 0.88 and 0.82 for water content, fat-free substance, and protein content of fat free substance, respectively. Fat tissue content, fat tissue mass, and lean tissue mass measured by MRI showed allometric relationships to lipid content, lipid mass, and protein mass determined by DT with correlations of 0.98, 0.87, and 0.98, respectively. Lean (measured by MRI) and protein (determined by DT) content of soft tissue was best fitted by a linear-quadratic polynomial and resulted in a correlation of 0.86. Allometric coefficients for change of percentages of chemical components, water (b=-0.036) and protein (b=0.106) in fat-free substance of empty body during growth were similar to those in the literature indicating the consistency of accretion rates of chemical components of the fat-free substance in different studies. Means for protein- and lipid-deposition rates (determined by DT) as well as lean tissue- and fat tissue deposition rates (measured by MRI) ranged from 95 to 154, 147 to 328, 373 to 420 and 129 to 254g in the different weight ranges. Variation between animals in protein (lean tissue) and lipid (fat tissue) deposition rate was large which can be exploited in order to identify QTL of these traits. PMID- 22061737 TI - The significance of the activity of glycogen debranching enzyme in glycolysis in porcine and bovine muscles. AB - The purpose of the study was to examine the activity of glycogen debranching enzyme, GDE, in porcine and bovine muscles differing in rate of contraction and oxidative capacity. The activity of GDE, the activity of phosphorylase, total glucose content, lactate content and pH were measured from meat samples taken 35min post-mortem and ultimate pH 24 or 48h post-mortem. Both GDE and phosphorylase are needed for the complete degradation of glycogen. In porcine muscles the activities of these glycogen degrading enzymes were higher than in bovine muscles. The activities were increasing with the increasing fast twitch and glycolytic character of a muscle of a given species. However, the increase in the activity of phosphorylase was greater than the increase in the activity of GDE. It was concluded that the GDE may restrict the rate of glycolysis in fast twitch muscles. PMID- 22061738 TI - Association of the polymorphism in the 5'-noncoding region of the bovine growth hormone receptor gene with meat production traits in Polish Black-and-White cattle. AB - Single and combined effects of polymorphisms in the 5'-noncoding region of the bovine growth hormone receptor (GHR) gene on the traits related to meat production were examined in Polish Black-and-White (BW; Friesian) cattle. Four single nucleotide polymorphisms (SNPs) located in the P1 promoter region were analysed. One-hundred and fifty young bulls were included in the study. The traits analysed were daily weight gain, feed intake and conversion, and carcass parameters. Individual SNPs had no effect on growth rates, feed consumption and conversion but showed marked effect on carcass composition traits. The (-/-) genotype at RFLP-AluI appeared favorable for weight of carcass, carcass dressing percentage, and weight of lean in valuable cuts. Animals with the RFLP-NsiI (+/+) genotype seemed better for most of the carcass parameters. In addition, statistically significant associations were found between combined GHR genotypes and feed consumption, carcass weight and dimensions. PMID- 22061739 TI - Acceptability of lamb meat from different producing systems and ageing time to German, Spanish and British consumers. AB - In the present study German (DE), Spanish (ES) and British (UK) consumers' acceptance of lamb from their own country compared to lamb from Uruguay (UY) was evaluated. Two-hundred consumers in each country evaluated tenderness, flavour and overall acceptability of four types of lamb, two from UY (light and heavy lambs aged 20 d) and 2 local (with two ageing times, 7 and 20 d). In each country 1.5cm-thick slices of lamb were evaluated by previously selected consumers in controlled conditions. DE and UK consumers showed significantly (P<0.05) different acceptability scores between samples, the lamb from heavier animals and aged 20 d being the most appreciated. On the other hand the majority of the ES consumers significantly (P<0.05) preferred the meat from lighter lambs. Production systems, cultural aspects and consumption habits seem to affect the acceptability of the lamb to the consumers. PMID- 22061740 TI - Pelvic suspension improves quality characteristics in M. semimembranosus from Swedish dual purpose young bulls. AB - To study whether pelvic suspension would improve tenderness in comparison with normal hanging from the achilles tendon, carcasses from 34 Swedish red and white young bulls were randomly selected at the slaughter line. The left sides of the carcasses were re-hanged by the pelvic bone before cooling whereas the right sides remained hanging from the achilles tendon. Quality characteristics and length and weight were studied for M. semimembranosus. Tenderness was measured by the Warner-Bratzler shear force method. Purge and cooking loss were determined and sarcomere length was measured. Pelvic suspension considerably affected the shape of M. semimembranosus; the length increased by 38% in comparison with achilles suspension. The elongation of the muscle was parallel with an increase in sarcomere length from 1.6 to 2.9MUm. The water-holding capacity was improved because both purge and cooking loss were lower for pelvic suspended carcasses. Tenderness was improved and the coefficient of variation between animals for Warner-Bratzler shear force was reduced from 26% for achilles tendon suspension to 12% for pelvic suspension. Likewise, the within-animal variation for shear force decreased significantly from 13.3% to 10.0%. Therefore, pelvic suspension seems to be a reliable method to reduce texture variability in M. semimembranosus from young bulls. PMID- 22061741 TI - Estimation of the genetic admixture composition of Iberian dry-cured ham samples using DNA multilocus genotypes. AB - Under current Spanish regulations, the pigs that provide the raw material for the preparation of the country's most appreciated meat-derived product, dry-cured Iberian ham, must be of a specific genetic composition. Only the Duroc breed is accepted for crossing with Iberian pigs, and a maximum of 50% of the Duroc genome is permitted in the animals used to make this ham. This paper describes a set of statistical procedures for detecting the 'breed composition' of Iberian ham via the use of multilocus genotypes obtained by the amplification of 25 microsatellite markers. The proposed procedure detected up to 20% of ham samples with a genetic composition incompatible with present legislation - either because the Duroc genome was present in a percentage greater than that permitted, or because of the significant presence (>25%) of white coat pig genomes. The probability of finding an illegal cured ham was greater in restaurants than in retail grocery stores, and in medium-low category restaurants or stores than in higher category establishments. PMID- 22061742 TI - Citric acid and sodium citrate effects on pink color development of cooked ground turkey irradiated pre- and post-cooking. AB - The effects of citric acid (0.15%, 0.3%) and sodium citrate (0.5%, 1.0%) on pink color development in ground turkey following irradiation (0, 2.5, 5.0kGy) were examined. Citric acid and sodium citrate had little effect on pink color when samples were irradiated prior to cooking. In contrast, when samples were cooked prior to irradiation, citric acid (0.3%) and sodium citrate (1.0%) reduced redness as indicated by eliminating a reflectance minimum at approximately 571nm, lessening greater reflectance in the red wavelength region, and preventing greater reducing conditions caused by irradiation. Citric acid significantly reduced pH and yields whereas sodium citrate reduced pH and yields to a lesser extent. Both citric acid and sodium citrate are potential ingredients that can be added during processing to prevent undesirable pink color in precooked irradiated ground turkey and therefore can result in greater acceptance of irradiated products by consumers. PMID- 22061743 TI - Sorting for beef tenderness using high performance liquid chromatography and capillary electrophoresis: A research note. AB - This study utilized two sampling methods to examine changes in sarcoplasmic proteins during aging of beef and their relation to tenderness. Water-soluble proteins either obtained by manually expressing exudates from the meat (drip) or by an extraction procedure using homogenization and centrifugation (ext) were analyzed for longissimus lumborum muscle using HPLC and capillary electrophoresis (CE) on days 2, 7, 10 and 14 postmortem. A peak that consistently increased with aging was identified using HPLC. Among nine peaks detected in the CE analysis, peak 9 (100kDa) that increased and peak 4 (30kDa) that decreased with aging were correlated (P<0.05) to tenderness as determined by Warner-Bratzler shear force (WBSF). For pooled data of all aging periods, drip sample explained the most variability (49%) in shear force compared to ext sample (25%) using HPLC analyses. At 2 days postmortem, a multiple linear regression model explained 83% of the variation in WBSF using CE-ext or HPLC-drip samples. Sixty percent of the variability in shear force was explained by CE-ext samples for day 7 data. The variability in shear force as explained by either drip or ext sample was less than 51 percent for 10 and 14 days postmortem data. The drip samples were comparable to ext samples in predicting WBSF values for both tough (>46N WBSF on day 2) and tender (<46N WBSF on day 2) strip loins using CE and HPLC procedure. Results suggest that a simple drip sampling may have a potential for use with either HPLC or CE analyses on day 2 postmortem for sorting carcasses into tenderness groups. PMID- 22061744 TI - Myofibrillar protein extracts from spent hen meat to improve whole muscle processed meats. AB - Myofibrillar protein (MP) from spent hen meat was used as an ingredient for chicken breasts and pork hams. Cooking loss (CL) and texture of both products were evaluated. Salt-soluble MP was extracted following centrifugation. A brine with 6% MP or a brine without MP were injected into meat to 20% of the original meat weight. CL was reduced in pork hams treated with 6% MP (P<0.05). Chicken breasts with 6% MP had greater hardness and gumminess than those without MP (P<0.05). Pork hams with 6% MP had greater hardness, gumminess and chewiness than those without MP (P<0.05). It was concluded MP from spent hen meat may be used to improve the functional properties of whole-muscle meat products. PMID- 22061745 TI - The effect of nutritional supplements on growth rate, stress responsiveness, muscle glycogen and meat tenderness in pastoral lambs. AB - Nutritional supplements and a magnesium bolus and were used in lambs in a 2*2 factorial design to investigate the effect on growth, preslaughter stress measurements, muscle glycogen, and meat quality. In total, 64 Perendale lambs were used (32.7+/-0.53 kg, mean+/-SEM). Feed supplemented animals received 150 g feed pellets day(-1) in addition to pasture grazing, and this increased growth from 183 to 207 g day(-1). Mean delivery of Mg from the boluses was 0.17 g day( 1) for 28 days, with no effect on growth rates, or any other of the variables measured. Urinary noradrenaline, adrenaline and cortisol did not differ between groups in the immediate pre-slaughter period. The meat ultimate pH was not different between groups and had a mean range of 5.47-5.53. Muscle residual glycogen did not differ between groups and had a mean range of 42-43 mmol kg(-1). Finally there were no differences in shear force values at all ageing times. The final shear force value of 2.5 kg F after 72 h ageing at 15 degrees C was a low value representing tender meat. These studies indicate that if nutrition is adequate and stress levels are low, there are no differences in meat tenderness of pasture fed lambs compared with those having feed supplements to increase growth rate. PMID- 22061746 TI - Processing characteristics of beef roasts made from high and normal pH bull inside rounds. AB - The processing characteristics of roasts manufactured from either high or normal pH bull inside rounds (semimembranosus and adductor muscles), which had been stored chilled or frozen, were investigated. Roasts were injected with a salt/phosphate brine and cooked to an internal temperature of 63 degrees C in a 70 degrees C water bath. High-pH meat that had been frozen had less purge than normal pH meat. However, pH did not affect purge from chilled meat. Meat pH and storage conditions did not affect retention of pumped brine. Cook yields were significantly (P<0.05) higher for roasts made from high pH meat (103.8 vs 98.8%). Raw and cooked meat colour was affected by meat pH but not storage condition. Cooking reduced the effect of pH on meat colour but cooked roasts manufactured from high pH meat were redder than roasts manufactured from normal pH meat. PMID- 22061747 TI - Monoclonal antibodies against troponin I for the detection of rendered muscle tissues in animal feedstuffs. AB - Regulatory controls to prevent the spread of BSE have prohibited the use of certain animal proteins in feed in several countries. Accurate analytical methods for detecting prohibited material in feedstuffs are needed to ensure compliance with the new regulations. Six IgG class monoclonal antibodies (MAbs) against troponin I (TnI), a thermostable marker protein, have been developed for the detection and differentiation of rendered muscle tissue in animal feed. MAbs 1F9, 2G3 and 7F7 reacted to TnI of all species, including mammalian, poultry and fish, while MAbs 7A12 and 8A12 recognized only mammalian TnI (porcine, bovine, ovine, equine, and deer). MAb 2A8 was able to differentiate TnI of ruminant origin (bovine, ovine and deer) from other species. Three indirect enzyme-linked immunosorbent assays (ELISAs) employing these MAbs were developed for the determination of animal muscle, mammalian muscle or ruminant muscle in animal feeds. PMID- 22061748 TI - The effect of food deprivation prior to slaughter on performance, behaviour and meat quality. AB - The effects of repeated food deprivation, prior to slaughter, on performance, feeding behaviour and meat quality of pigs was examined. Three experimental treatments were compared. In treatment 1 pigs had ad libitum access to feed up to the point of loading on the day of slaughter. Treatment 2 involved a 12-h fast prior to slaughter and treatment 3 involved a 20-h fast prior to slaughter. Pigs were slaughtered on a weight basis therefore each pen was emptied over a period of weeks. This meant some pigs experienced repeated food deprivation. The feeding pattern of pigs which were deprived of food for 12 h was very similar to that observed before feed restriction. Pigs which were deprived of food for 20 h spent significantly more time at the feeder post fasting. This was particularly marked during the first 2-3 h when access to feed was restored. Feed deprivation for 12 h prior to slaughter did not adversely affect performance, carcass weight, meat quality or welfare in the present study. Fasting for 20 h reduced carcass weight by 1 kg, which was not statistically significant but could result in financial losses related to carcass weight. The negative effects on meat quality, of repeated feed deprivation, resulted from slower growth rates rather than feed deprivation per se. PMID- 22061749 TI - Processing and sensory characteristics of cooked roast beef: effect of breed, age, gender and storage conditions. AB - Two separate experiments investigated the effect of breed (Bos indicus, Bos indicus*and Bos taurus), gender/age and chilled and frozen storage on the processing characteristics of roasts made from inside rounds (semimembranosus, adductor and gracilis muscles). Roasts were injected with a salt/phosphate brine and cooked to an internal temperature of 63 degrees C. Freezing the meat increased purge lost from the raw meat. Country of origin had no significant effect on cook yield. Sensory evaluations with a US consumer panel indicated only slight sensory differences due to country of origin and breed but a significant effect from storage regime. Tenderness comparisons between breeds were confounded by country of origin and indicated that roast beef from inside rounds from Brahman cattle had lower WBS values than roast beef made from inside rounds from British cattle. Although breed and age/gender often significantly affected processing characteristics of the roasts, differences were small and would have little practical or economic importance for selecting the type of meat for this market sector. PMID- 22061750 TI - Effects of halothane genotype and pre-slaughter treatment on pig meat quality. Part 1. Post mortem metabolism, meat quality indicators and sensory traits of m. Longissimus lumborum. AB - Forty-eight castrated F(2) offspring of Pietrain and Large White pigs were allocated to a 3 * 2 factorial design in order to study the interactive effect of halothane genotype (NN, Nn and nn) and pre-slaughter treatment [referred to as 'Experimental' (EXP) and 'Commercial-like' (COL) conditions; the latter combining short transportation, mixing unfamiliar pigs and slaughtering shortly after transport] on muscle post mortem changes and meat quality. The pigs were slaughtered over 4 days. Pre-slaughter glycogen depletion in M. longissimus lumborum (LL) was greater in the nn pigs, compared with the two other genotypes. Lactate accumulation post mortem in LL muscle was greater and the pH value at 40 min post mortem was lower in nn compared with NN pigs. Nn pigs were close to nn pigs for lactate accumulation and showed intermediate pH values in the LL muscle. In the M. semimembranosus (SM), NN and Nn pigs showed the same rate of post mortem changes, as evidenced by similar glycogen, lactate, creatine phosphate and ATP levels, and pH values at 40 min post mortem. Pre-slaughter treatment did not affect the rate of post mortem changes in both muscles and no interactive effect with halothane genotype was found. The pigs slaughtered under the 'COL' conditions had a significantly higher ultimate pH in the LL and SM muscles than those slaughtered under the 'EXP' conditions. The LL muscle from nn pigs was paler (higher L*) than that of NN and Nn pigs. In SM muscle, Nn pigs showed a significantly higher L* value than NN pigs. Drip loss of the LL muscle was significantly higher in nn compared with NN pigs, the heterozygous pigs being intermediate. Sensory evaluation of the LL muscle showed that nn pigs had a lower colour intensity and colour homogeneity of raw meat than NN and Nn pigs. Tenderness was significantly lower in nn compared with NN pigs, the Nn pigs being intermediate. Pre-slaughter treatment significantly increased ultimate pH in both muscles (LL and SM) but did not affect significantly the rate of pH fall (pH(40)). It did not affect any of the meat quality traits and no interactive effect with halothane genotype was found. These results confirmed the influence of the halothane gene on the kinetics of muscle post mortem changes and related meat quality traits. They also confirmed the intermediate position of heterozygous pigs in terms of meat quality. PMID- 22061751 TI - Effects of halothane genotype and pre-slaughter treatment on pig meat quality. Part 2. Physico-chemical traits of cured-cooked ham and sensory traits of cured cooked and dry-cured hams. AB - Forty-eight castrated F(2) offspring of Pietrain and Large White pigs were allocated to a 3*2 factorial design in order to study the interactive effect of halothane genotype (NN, Nn and nn) and pre-slaughter treatment (referred to as 'Experimental' (EXP) and 'Commercial-like' (COL) conditions; the latter involving short transportation, mixing unfamiliar pigs and slaughtering shortly after transport) on the qualities of cured-cooked and dry-cured hams. At 24 h post mortem, the hams were collected and assigned to cured-cooked (right ham) and dry cured (left ham) ham processing. A sample of M. semimembranosus (SM) was collected before cooked ham processing, was used for chemical composition analysis, cured and then cooked at various temperatures. Cooking losses and compression tests were carried out after cooking on these SM samples. The water and collagen content of SM muscle was significantly higher in nn pigs compared with the two other genotypes. At all cooking temperatures (60, 65 and 70 degrees C), SM muscles from nn pigs showed higher cooking losses and instrumentally assessed toughness than the other genotypes, the heterozygous pigs being intermediate. The technological yield of cured-cooked ham processing was lower in nn, compared with NN and Nn animals. Cooked hams from nn pigs were drier, tougher, stringier and less smooth than NN and Nn pigs. The heterozygous pigs were similar to normal pigs for all texture characteristics with the exception of toughness for which they got a significantly higher score than NN pigs. The pigs slaughtered under the COL conditions had a better slice cohesiveness and a significantly lower dryness, than pigs slaughtered under the EXP conditions. The effect of HAL genotype on slice cohesiveness was significant only when pigs were slaughtered under the EXP conditions. Dry-cured hams from nn pigs showed significantly more visual defects, but were less tough, smoother and more fondant (softer) than NN and Nn pigs. The dry-cured hams from pigs slaughtered under the COL conditions had a better cohesiveness between muscles and a more intense yellow colour of fat than those from pigs slaughtered under the EXP conditions. COL pigs were also judged significantly less tough, smoother and more fondant than EXP ones. Overall, the effects of pre-slaughter treatment were small compared with those of the HAL genotype. The effects of HAL genotype on the sensory traits of cured-cooked ham were similar to those reported for fresh meat. However, the good textural characteristics of dry-cured ham processed from HAL positive pigs are somewhat surprising and need to be confirmed. PMID- 22061752 TI - Influence of outdoor rearing and indoor temperature on growth performance, carcass, adipose tissue and muscle traits in pigs, and on the technological and eating quality of dry-cured hams. AB - The effects of restricted outdoor rearing during winter (W) or summer (S), and the influence of indoor ambient temperature [17 degrees C (I17) vs. 24 degrees C (I24), the latter being considered as control] on pig growth performance, carcass, muscular and adipose tissue traits, and technological and eating quality of dry-cured hams were evaluated. I17 pigs exhibited higher, whereas W had similar and S lower growth rates than the controls (P<0.001). Carcass traits were not different between groups, except in lower back fat weights of S and W pigs (P<0.01). Decrease in environmental temperature affected the fatty acid composition of the back fat leading to higher MUFA and lower SFA and PUFA contents (P<0.001) in I17 and W pigs, whereas S pigs exhibited higher PUFA levels (P<0.001) and fat firmness (P<0.01) than the controls. Rearing system did not significantly influence the intramuscular fat content of Semimembranosus (P=0.08), and had no effect on ultimate pH. In the Longissimus lumborum, percentage and relative area of alphaR fibers increased in W pigs (P<0.05), but citrate synthase activity did not differ between groups. I17 and W hams exhibited higher processing yields of dry-cured hams than controls (P<0.05). Sensory analyses showed that pig rearing conditions influenced the product appearance, the I17 and W hams exhibiting lower homogeneity (P<0.01) and intensity (P<0.05) of colour, and higher marbling scores (P<0.01) than I24 hams, but had no influence on texture or flavour. PMID- 22061753 TI - Effects of alpha-tocopherol level in raw venison on lipid oxidation and volatiles during storage. AB - Relationships between alpha-tocopherol concentration in the muscle and development of lipid oxidation or volatiles in raw venison were studied. Fourteen Japanese Shika Deer (Cervus nippon) were fed various amounts (0-3.0 g of alpha tocopheryl acetate per animal) during the different periods (0-37 days) and then M. longissimus thoracium et lumborum (LD muscles) with a range of alpha tocopherol concentrations (4.1-15.1 mg/kg tissue) were obtained. For stabilizing the lipid during storage for 11 days under air, over ca. 9 mg of alpha-tocopherol per kg tissue were required based on levels of 2-thiobarbituric acid reacting substances (TBARS) numbers. Nine compounds were identified in headspace volatiles, and one of the volatiles was hexanal which has been recognized as off flavour component. For depressing the hexanal evolution, at least ca. 9 mg of alpha-tocopherol per kg tissue were also required for 11 days' storage. This value was much higher than other species. The reasons for higher requirement of alpha-tocopherol were possibly due to the higher concentration of unsaturated fatty acid and myoglobin in venison. PMID- 22061754 TI - Effects of halothane gene and pre-slaughter treatment on meat quality and welfare from two pig crosses. AB - Pigs from crosses of a Pietrain (Pi) and a Large White*Pietrain (LwPi) heterozygous (Nn) boar lines with Landrace*Large White homozygous negative (NN) sows, were used to study the effect of halothane gene and pre-slaughter treatment on animal welfare and meat quality. A total of 83 gilts (47 NN and 36 Nn) were assigned to a long treatment (3 h 15 min transport and 12 h lairage) and 73 (39 NN and 34 Nn) to a short treatment (30 min transport and 2 h lairage). Heart rate was recorded throughout loading and transport. Blood samples were collected before loading, after transport, and at exsanguination to measure cortisol, creatine phospho-kinase (CPK) and lactate dehydrogenase (LDH). Carcasses were classified and commercial cutting was carried out. Meat quality was assessed on the Longissimus thoracis muscle by measuring electrical conductivity (PQM), colour (Minolta CR 200 and Japanese scale) and ultimate pH. Loin drip losses were assessed at 24 h. Halothane carriers showed a higher increase in cortisol levels after transport and exsanguination in the long treatment (P<0.05) as well as in LDH and CPK after exsanguination in the short treatment (P<0.05). In this treatment, halothane-free pigs recovered during lairage when comparing LDH and CPK increases after exsanguination to their increases after transport. No effect of the halothane gene on heart rate was observed. Pi sired pigs were leaner and had higher yields of leg and loin compared with LwPi sired pigs (P<0.001), but no differences in meat quality were observed between crosses. Halothane carriers had a higher estimated lean content (P<0.01) and shoulder and leg yields (P<0.01), but poorer meat quality than non-carriers (i.e. higher incidence of PSE meat, P<0.001). Although pre-slaughter treatment and halothane genotype did not significantly affect pHu, significantly higher L*, a* and b* values found in the short treatment and Nn individuals indicated paler meat. These results suggest that for improving meat quality and welfare the halothane gene should be removed from breeding schemes. PMID- 22061755 TI - Substitution of nitrite by sorbate and the effect on properties of mortadella. AB - Investigation of substitution of nitrite by sorbate in mortadella involved preparation of the product with nitrite-sorbate combinations and controls of nitrite and sorbate alone. The results revealed that mortadella samples made with sorbate alone were not sensorily acceptable and had the highest TBA values. Mortadella prepared with nitrite alone was acceptable in all respects but showed the highest percentage of nitrite losses during storage. Nitrite-sorbate combinations were not significantly different with regard to color, flavor, and overall acceptability, compared to nitrite alone. These combinations showed lower TBA values. The study also demonstrated the importance of refrigerated storage for mortadella. Overall, the results indicated that complete nitrite replacement by sorbate is not possible in mortadella, but partial replacement with sorbate is acceptable. PMID- 22061756 TI - Inhibition of mutagenic N-nitroso compound formation in sausage samples by using l-ascorbic acid and alpha-tocopherol. AB - In this study 24 samples of sausage with different amounts of nitrite, l-ascorbic acid and alpha-tocopherol were prepared in order to determine the inhibitory effects of l-ascorbic acid and alpha-tocopherol as reductants against formation of mutagenic N-nitroso compounds that form in cured meat products. These mutagenic N-nitroso compounds were extracted by phosphate buffer and ethylacetate. The mutagenicity of extracts were investigated by salmonella/microsome assay. The number of revertants indicated the N-nitroso compounds content. Among the Salmonella typhimurium strains tested, the revertants of S. typhimurium TA100 were significantly reduced (P<0.5) by 60% when reductants were added to the samples. PMID- 22061757 TI - Manipulation of critical quality indicators and attributes in pork through vitamin E supplementation, muscle glycogen reducing finishing feeding and pre slaughter stress. AB - The combination of a muscle glycogen reducing diet or a standard diet (control group) with normal (80 mg/kg) and high vitamin E levels (500 mg/kg) and exercise immediately prior to slaughter was used on 56 pigs to investigate the influence on meat quality indicators (pH and temperature) and attributes (drip loss, colour and Warner-Bratzler shear force). The drip loss was reduced in M. longissimus dorsi, M. biceps femoris and M. semimembranosus in pigs given the muscle glycogen reducing diet compared with the control groups, the greatest effect was seen in exercised pigs. These results can be explained by an early post mortem reduction in glycometabolism in pigs fed muscle glycogen reducing diets rather than by an increase in ultimate pH. Noticeably, high dietary vitamin E level increased muscle glycogen stores by about 10% on the day prior to slaughter but not on the day of slaughter in both dietary groups compared with the low dietary vitamin E level, which in fact reduced rather than improved the water-holding capacity, especially in pigs fed the standard diet. PMID- 22061758 TI - The calibration temperature of pH-glass electrodes: significance for meat quality classification. AB - In this short communication we show important factors concerning pH measurements in pork. The purpose of the study was to investigate the effect of the calibration temperature of pH-buffer and of the pH-electrode on pH measured 1-120 min post mortem in pork, and to evaluate its significance for prediction of meat quality. The calibration temperature of pH-electrodes as well as the sample temperature is essential for pH measurements, as pH measurements are highly temperature-dependent. This is especially important when using pH measurement for prediction of meat quality or when different experiments are compared. We have used two calibration temperatures of 15 degrees C (normal) and 35 degrees C (modified) in the present investigation. Based on our findings, we therefore recommend a buffer and electrode temperature of 35 degrees C as a standard procedure for measuring pH early post mortem. As a minimum the pH should be presented along with the measuring and calibrating temperatures. PMID- 22061761 TI - "Strategic finishing feeding as a tool in the control of pork quality" by K. Rosenvold, H.N. Laerke, S.K. Jensen, A.K. Karlsson, K. Lundstrom, H.J. Andersen, Meat Science 59, 397-406. PMID- 22061759 TI - Influence of meat quality and NaCl percentage on glutathione peroxidase activity and values for acid-reactive substances of raw and dry-cured Longissimus dorsi. AB - Fresh and dry-cured porcine loins (Longissimus dorsi) were analysed for glutathione peroxidase (GSHPx) activity and acid reactive substances (TBARS) in order to assess the influence of meat quality and salt (NaCl) concentration on oxidative stability. The results showed lower GSHPx activity and higher TBA levels in normal meat than in PSE meat indicating a higher oxidative stress in normal meat quality. GSHPx remained active at the end of the curing process. Higher salt concentration led to lower enzyme activity and TBARS values prompted the thought of a double role of NaCl as an enzyme inhibitor and as an antioxidant molecule. PMID- 22061763 TI - Activity of cathepsin B, D, H and L in Spanish dry-cured ham of normal and defective texture. AB - Thirty-six specimens of Spanish dry-cured ham from 18 different batches were studied to determine the influence of endogenous enzymes on the textural quality of the end product. It was shown that, the residual enzyme activity of cathepsins B+L is a reliable indicator of textural defects associated with strong proteolysis in Spanish dry-cured ham. In contrast, the activity of cathepsin B, which varied widely among samples, was less influential. Salt levels can have a moderate effect on the residual enzyme activities. Other compositional parameters also influence the properties of the end product; the amount of protein in semimembranosus muscle was found to be less and the moisture greater in texturally defective specimens. Also, the efficiency of the drying-curing process was less in hams yielding poor textures. PMID- 22061764 TI - Determination of the buffering capacity of postrigor meat. AB - Since 1938, several studies on buffering capacity of postrigor meat have been presented. As the methods used have varied considerably it is important to know how to compare the results. The method of titration, mainly the amount of dilution used, has a significant effect on the shape of the obtained buffering capacity curve. When a dilute solution is used, the curve has distinct maximum and minimum points. With less dilution, the buffering capacity curve approaches a shape with no distinct minimum and maximum points in pH range 5.5-7.0. However, it seems possible to estimate the buffering capacity of meat from data based on titrations made with different dilutions. A mean value for buffering capacity valid in pH range 5.5-7.0 can be estimated from titrations made with dilution ratios 1:10 and 1:1. The mean buffering capacity values in pH range 5.5-7.0 were for beef m. longissimus muscle 51 mmol H(+)/(pH*kg), for pork m. longissimus 52 mmol H(+)/(pH*kg), for beef m. triceps brachii 48 mmol H(+)/(pH*kg) and for pork m. triceps brachii 45 mmol H(+)/(pH*kg). For broiler breast and broiler leg-thigh muscles the corresponding values were 58 and 41 mmol H(+)/(pH*kg). PMID- 22061765 TI - Differentiation of the species ostrich (Struthio camelus) and emu (Dromaius novaehollandiae) by polymerase chain reaction using an ostrich-specific primer pair. AB - Through polymerase chain reaction a zone of the gene for the cytochrome b of ostrich (Struthio camelus) mitochondrial DNA was amplified using a primer pair which permits to identify the ostrich and differentiate it from the emu (Dromaius novaehollandiae), thus giving different size fragment; in the ostrich of about 543 bp and in the emu of about 229 bp. This has been obtained without adopting other techniques such as, e.g., the fragment digestion by means of suitable restriction enzymes or single strand conformational polymorphism (SSCP). PMID- 22061766 TI - A research note on factors affecting the determination of myofibrillar fragmentation. AB - The myofibrillar fragmentation index (MFI) was determined for a section of ovine Longissimus muscle, aged for either 1 or 3 days and processed from either the fresh or frozen state. Additionally samples were homogenized at one of three speeds (5000, 10,000 or 15,000 rpm). Speed of homogenisation and 'state' of the sample both had a significant effect (P < 0.001) on MFI values as did the interaction between speed and state (P < 0.001), with other interactions terms not being significant. Age of the sample had no significant (P > 0.05) effect on MFI values with least square means (s.e.) for Day 1 and Day 3 being 92 and 93 (1.16), respectively. As homogenisation speed increased, the difference between values for fresh and frozen samples was diminished, such that at 15,000 rpm there was no effect of 'state' on values. Overall the 'state' and the speed of homogenisation have a large impact on values and there was more variation between samples at the slowest speed (5000 rpm). At the slowest speed myofibrils consist of more sarcomeres and can be observed to still exhibit intermyofibril linkages. The results suggest a homogenisation speed of 15,000 rpm was preferable when determining MFI values. PMID- 22061767 TI - Sire variation in fatty acid composition of crossbred Wagyu steers and heifers. AB - Effects of sires on lipid composition of subcutaneous adipose tissue and longissimus dorsi muscle were studied using 113 F(1) heifer and steer calves sired by eight Wagyu bulls out of three different cow herds. Wagyu sires were used and grouped as Old (n=6) and New (n =2) sires, respectively, based on the chronological order in which they were imported into the US. Animals were fed a backgrounding diet for 112 days consisting of an 80:20 ratio of roughage:concentrate, then grazed on orchard grass and bluegrass for 84 days, and finished on a 10:90 ratio of roughage:concentrate diet for 231 days in a feedlot. For longissimus dorsi muscle, progeny from Old sires had higher (P<0.05) monounsaturated to saturated fatty acid ratios (MUFA:SFA) than progeny of New sires. There were also differences (P<0.05) among individual sires for polyunsaturated to saturated fatty acid ratio (PUFA:SFA) (0.05-0.08) and MUFA:SFA (1.03-1.21). Progeny of Angus cows at Washington State University (WSU) had lower (P<0.05) MUFA:SFA and lower SFA than progeny of WSU crossbred and commercial cows. Steers had lower (P<0.05) MUFA:SFA and higher (P<0.05) SFA than heifers. For subcutaneous fat, heifers had higher levels (P<0.05) of linoleic acid (C18:2) and PUFA:SFA than the steers. Means for ether extractable fat in longissimus dorsi muscle differed among sires (P<0.05) and ranged from 7.58 to 13.13%. Progeny from WSU Angus cows had higher (P<0.05) ether extractable fat than WSU crossbred and commercial cows. Cholesterol content of longissimus dorsi muscle was not influenced by sire, cow herd or sex (P>0.05). PMID- 22061768 TI - Protein quality and microbiological changes in aerobically- or vacuum-packaged, irradiated fresh pork loins. AB - The effect of gamma-irradiation on the physicochemical, organoleptic and microbiological properties of pork was studied, during 43 days of storage at 4+/ 1 degrees C. Irradiation treatments were carried out under air or vacuum packaging on fresh pork loins at a dose of 6 kGy, at two different dose rates: 2 kGy/h and 20 kGy/h. The loins were evaluated for protein sulphydryl content and emulsifying capacity, surface hydrophobicity of proteins and sensorial evaluation. Regardless of the type of packaging and dose rate of irradiation, all irradiated pork samples were effectively prevented from bacterial spoilage for at least 43 days. Meat redness and texture of irradiated loins were relatively well preserved during the storage period, especially when samples were stored under vacuum. Overall, the physicochemical and organoleptic changes in pork loins appeared to be relatively little affected by the 6 kGy dose. No marked changes in emulsifying capacity and protein sulphydryl content of proteins were noted throughout the storage period. However, the hydrophobicity was reduced (P?0.05) by the faster dose rate of irradiation and by longer storage. PMID- 22061769 TI - Relationship between fat depots in carcasses of beef bulls and effect on meat colour and tenderness. AB - Four hundred and thirty-three double-muscled and two hundred and two non-double muscled Belgian Blue bulls, with mean cold carcass weights of 470+/-27 and 414+/ 33 kg, respectively, were studied to investigate the relationships between the SEUROP fat grade, the anatomical fat content in the carcass (adipose tissue) and the chemical fat content in the Longissimus thoracis. The relationships between the shear force value and the lightness of the meat and fat characteristics were also studied. A moderate correlation was found between the fat characteristics within each data set with correlation coefficients, ranging from 0.4 to 0.6. The correlation coefficients increased to 0.70-0.85 when the data sets were pooled. Fat characteristics of the carcass and meat showed only limited predictive power (R(2)<0.15) for meat tenderness and colour. This study also shows that double muscled animals belong to a sub-population of the Belgian Blue breed rather than deviants from the non-double-muscled animal. PMID- 22061770 TI - Relationship between RN(-) genotype and drip loss in meat from Danish pigs. AB - The presence of the RN(-)-gene determined in 72 halothane negative Danish pigs, either by a direct genotyping or the glycolytic potential of the meat, in relation to drip loss, was investigated. The drip loss in the M. longissimus dorsi from RN-carriers (n=26), as determined by genotyping was 9.9% compared to 8.6% in non-carriers (n=46) (P=0.07). When a glycolytic potential of >230 MUmol lactate/g meat was used to differentiate between carriers and non carriers of the RN(-)-gene, the drip loss in carriers was 10.6% (n=17) compared to 8.7% in non carriers (n=55) (P<0.01). These results suggest that the presence of the RN(-) gene in Danish slaughter pigs only partially explains the large variation in drip loss observed in Danish pork. PMID- 22061771 TI - Evaluation of pork color by using computer vision. AB - The objective of this study was to determine the potential of computer vision technology for evaluating fresh pork loin color. Software was developed to segment pork loin images into background, muscle and fat. Color image features were then extracted from segmented images. Features used in this study included mean and standard deviation of red, green, and blue bands of the segmented muscle area. Sensory scores were obtained for the color characteristics of the lean meat from a trained panel using a 5-point color scale. The scores were based on visual perception and ranged from 1 to 5. Both statistical and neural network models were employed to predict the color scores by using the image features as inputs. The statistical model used partial least squares technique to derive latent variables. The latent variables were subsequently used in a multiple linear regression. The neural network used a back-propagation learning algorithm. Correlation coefficients between predicted and original sensory scores were 0.75 and 0.52 for neural network and statistical models, respectively. Prediction error was the difference between average sensory score and the predicted color score. An error of 0.6 or lower was considered negligible from a practical viewpoint. For 93.2% of the 44 pork loin samples, prediction error was lower than 0.6 in neural network modeling. In addition, 84.1% of the samples gave an error lower than 0.6 in the statistical predictions. Results of this study showed that an image processing system in conjunction with a neural network is an effective tool for evaluating fresh pork color. PMID- 22061772 TI - The effects of dietary alpha-tocopheryl acetate supplementation and modified atmosphere packaging (MAP) on the quality of lamb patties. AB - The effects of dietary alpha-tocopheryl acetate supplementation and/or packaging on the quality of lamb patties were investigated. Ewes (n=12) were selected and scanned to assess pregnancy. They were divided into two groups (n=6). The control group was fed a non-supplemented diet of 20 mg alpha-tocopheryl acetate/kg feed/day for 9 weeks ante-parturition and 3 weeks post-parturition. The lambs were weaned at 3 weeks and fed either the non-supplemented or supplemented diet for 10 weeks prior to slaughter. The M. longissimus dorsi from each carcass from each dietary group was stored at -20 degrees C for 7 months. Patties were formed from supplemented or control minced m. longissimus dorsi and held in either modified atmosphere packs (MAP) under atmospheres of 70:30, 80:20 or 90:10 CO(2):O(2), under vacuum or in overwrapped trays. All packs were held under refrigerated (4 degrees C, 616 lux) display for a period of 10 days. Patties were assessed for oxidative and colour stability on days 0, 2, 4, 6, 8 and 10. With each type of pack, dietary alpha-tocopheryl acetate supplementation significantly increased oxidative and colour stability compared to control patties. As oxygen concentrations increased in MAP packs, colour stability was enhanced but the rate of lipid oxidation increased. Vacuum packaged patties had significantly (P<0.05) higher Hunter 'a' values, lower proportions of metmyoglobin and lower TBARS numbers than those held under all other forms of packaging. Aerobically packaged patties had lower Hunter 'a' values, higher proportions of metmyoglobin and lower TBARS numbers compared to MAP patties. PMID- 22061773 TI - Effects of three preservative agents on the shelf life of vacuum packaged Chinese style sausage stored at 20 degrees C. AB - The influence of 3% sorbitol, 3% sodium lactate and 100 mg/kg nisin on the shelf life of vacuum packaged Chinese-style sausage stored at 20 degrees C was studied. Growth of microbiological populations (aerobe, anaerobe, lactic acid bacteria, leuconostocs) and slime formation on the sausage were not retarded during storage by addition of nisin. Sorbitol lowered the initial water activity of the sausage, however, microbiological spoilage accompanied with pH decline, increase in volatile basic nitrogen compounds and a sour odour defect were observed after 10 days storage. Sodium lactate was bacteriostatic as it inhibited microbial as well as chemical changes during storage so that the shelf life was 25 days at 20 degrees C. The dextran content of the vacuum packaged Chinese-style sausage indicated the spoilage 2-3 days earlier than that seen by other chemical assays or sensory evaluation. PMID- 22061774 TI - Effect of dietary energy and protein levels on fatty acid composition of intramuscular fat in double-muscled Belgian Blue bulls. AB - Seventy six Belgian Blue (BB) bulls, with double-muscled conformation, were randomly allocated to six dietary treatments in a 2 * 3 factorial experiment. The treatments included low (N(L)=127 g CP/kg DM), medium (N(M)=153 g CP/kg DM) and high (N(H)=172 g CP/kg DM) levels of dietary protein in combination with low (E(L)=7.38 MJ ME/kg DM) and high (E(H)=8.03 MJ ME/kg DM) levels of dietary energy. Fatty acid composition was determined on total lipid samples of the M. longissimus thoracis of all animals and on the separated triacylglycerol and polar lipid fatty acid fractions of the medium-protein group. Dietary energy and protein levels influenced the carcass characteristics of BB bulls but the effects were small. Carcass fat cover score, carcass fat content and intramuscular fat content were slightly but significantly higher in the animals on the high versus the low energy diets. The overall intramuscular fat content was very low (<1%) and the overall polyunsaturated:saturated fatty acid ratio (0.39) high compared to normal figures for beef. The high versus the low dietary energy level increased the monounsaturated (P<0.001) and decreased the polyunsaturated (P<0.001) fatty acid proportion with no change in the saturated fatty acid proportion. This may have been due in part to the addition of beef tallow to increase the energy level of the diet. Concomitant shifts in the individual fatty acids included increased proportions of C14:0 (P<0.001), C16:0 (P<0.03), C16:1 (P<0.01), C18:1 (P<0.001) and decreased proportions of C18:2 (P<0.001) and C20:4 (P<0.001). Increasing dietary protein levels had inconsistent effects on the fatty acid profiles. The proportion of polar lipid fatty acids in the total fatty acids was 0.34 and 0.25 for the E(L) and E(H) group, respectively, in the Nm treatment group. Changes in fatty acid proportions of the triacylglycerol fatty acid fraction were similar to those seen in the total lipid fatty acids when related to dietary energy level, but no significant changes in the polar lipid fatty acid proportions were observed. Significant linear relationships were found between measures of carcass and muscle fatness and fatty acid proportions. With increasing muscle total fatty acid content, saturated and monounsaturated fatty acid proportions increased (r=0.38 and r=0.55, respectively, P<0.01) and the polyunsaturated fatty acid proportion decreased (r=-0.73, P<0.01). The diet had some effects but the relatively unsaturated intramuscular fatty acid composition was mainly related to the low total fat content of the BB animals. PMID- 22061775 TI - Optimization of salt, olive oil and pectin level for low-fat frankfurters produced by replacing pork backfat with olive oil. AB - Response surface methodology was used to determine the optimum salt level (1.3 2.1%) and pectin level (0.25-1.0%) when olive oil replaced pork backfat (0-100%) for the production of highly acceptable low-fat frankfurters (9% fat, 13% protein). The test ingredients significantly affected (P<0.05) jelly separation of the batter, skin strength, hardness, saltiness, odour and taste and the overall acceptability of the low-fat frankfurters. Batters with high pectin levels recorded the highest (P<0.05) jelly separation. Low-fat frankfurters with high salt levels tended to have very hard skins and increased (P<0.05) saltiness while those with a high pectin level were very soft, tasted like cream and had the lowest (P<0.05) score for odour and taste. The low-fat frankfurters with 1.8 2.1% salt, 0-35% olive oil and 0.25-0.45% pectin had the highest overall acceptability. However, low-fat frankfurters produced with 1.3% salt, 0.25-0.30% pectin and 80-100% olive oil were also acceptable. Such low-fat frankfurters, compared to commercial products, have a 48% lower salt content (from 2.5 to 1.3%) and 66.6% lower fat content (from 30 to 10%), in which 80-100% of the added fat is olive oil. Further research is needed to improve the acceptability of these frankfurters. PMID- 22061776 TI - Carcass and meat quality in light lambs from different fat classes in the EU carcass classification system. AB - Ninety commercial lamb carcasses were analysed according to the four different fat classes in the light lamb European classification system. Shoulder fat increased 3%, muscle decreased 2% and bone decreased 1% for each class increase. No significant differences were found among fat classes regarding pH, WHC, cooking losses, juiciness, myoglobin content, meat colour measured immediately after cutting (L*, a*, b*), odour intensity or flavour quality. Some differences were found in colour evolution through ageing. Shear force decreased and tenderness and flavour intensity increased with fat class but this effect was only significant in the leanest animals. PMID- 22061777 TI - Influence of direct and delayed chilling of excised female buffalo muscles on their textural quality. AB - The excised muscles from the left half of 6 carcasses of old female buffaloes (4 5 years of age) were held, soon after slaughter, at the temperature of 2-3 degrees C for 24 h (direct chilling) and those from the right half at ambient temperature (26+/-2 degrees C) up to 6 h postmortem followed by chilling at 2-3 degrees C for 18 h (delayed chilling) in order to study the improvement in the texture quality of muscles. During the delayed chilling, the muscle pH decreased to 6.0 (from the initial value of 6.5) in 3 h whereas it took 5-6 h in direct chilling. Reduction in Instron firmness values was 10.3-33.6% and that in cohesiveness values was 13.2-22.2% in delayed chilled muscles compared to direct chilled ones when cooked muscles were sheared along or across the muscle fibres. These observations were statistically significant (P? 0.001) indicating a definite improvement in the texture quality of muscles subjected to delayed chilling. However, no definite trend was observed in the values of elasticity, cooking loss and water holding capacity of muscles due to direct or delayed chilling. PMID- 22061778 TI - Animal Welfare and Meat Science N.G.Gregory, 1998, Wallingford: CABI Publishing. PMID- 22061779 TI - Erratum to "Effect of dietary vitamin E supplementation on the colour and lipid stability of fresh, frozen and vacuum-packaged beef" [Meat Science, 52(1) (1999), 95]. PMID- 22061781 TI - High-oxygen packaging atmosphere influences protein oxidation and tenderness of porcine longissimus dorsi during chill storage. AB - The effect of modified atmosphere packaging (70% O(2)/30% CO(2)) and skin packaging (no oxygen) on protein oxidation and texture of longissimus dorsi was investigated during storage for 14 days at 4 degrees C. High oxygen atmosphere resulted in reduced tenderness and juiciness and SDS-PAGE revealed cross-linking of myosin heavy chain through disulfide bonding, and the content of protein thiols was reduced indicating protein oxidation. Myofibril fragmentation was reduced in meat stored in high oxygen atmosphere indicating less proteolysis and/or cross-linking of proteins. Protein carbonyl content was not affected by the packaging atmospheres. This study shows that packaging in modified atmosphere containing a high level of oxygen can result in protein cross-linking and reduced tenderness and juiciness of the meat. PMID- 22061780 TI - Inhibition of prolyl hydroxylases by dimethyloxaloylglycine after stroke reduces ischemic brain injury and requires hypoxia inducible factor-1alpha. AB - Pathological oxygen deprivation inhibits prolyl hydroxylase (PHD) activity and stimulates a protective cellular oxygen-sensing response in part through the stabilization and activation of the Hypoxia Inducible Factor (HIF) 1alpha transcription factor. The present investigation tested the therapeutic potential of enhanced activation of oxygen-sensing pathways by competitive pharmacologic PHD inhibition after stroke, hypothesizing that post-ischemic PHD inhibition would reduce neuronal cell death and require the activation of HIF-1alpha. The PHD inhibitor dimethyloxaloylglycine (DMOG, 100 MUM) reduced cell death by oxygen glucose deprivation (OGD), an in vitro model of ischemia, and the protection required HIF-1alpha. In vivo, DMOG (50 mg/kg, i.p.) administered 30 or 60 min after distal occlusion of the middle cerebral artery (MCA) in mice enhanced the activation of HIF-1alpha protein, enhanced transcription of the HIF-regulated genes vascular endothelial growth factor, erythropoietin, endothelial nitric oxide synthase, and pyruvate dehydrogenase kinase-1, reduced ischemic infarct volume and activation of the pro-apoptotic caspase-3 protein, reduced behavioral deficits after stroke, and reduced the loss of local blood flow in the MCA territory after stroke. Inhibition of HIF-1alpha in vivo by Digoxin or Acriflavine abrogated the infarct sparing properties of DMOG. These data suggest that supplemental activation of oxygen-sensing pathways after stroke may provide a clinically applicable intervention for the promotion of neurovascular cell survival after ischemia. PMID- 22061782 TI - Composition and physicochemical characteristics of restructured beef steaks containing walnuts as affected by cooking method. AB - The study was conducted to determine the influence of various cooking methods - conventional oven, microwave oven, electric grill and pan-frying on the composition and physicochemical characteristics of restructured beef steaks formulated as low fat (L, 2.0% fat), medium fat (M, 13.0% fat) and 20% added walnut (W, 12.6% fat). Composition, retention coefficients for different compounds, cooking loss (CL) and texture were affected by both formulation and cooking. There was considerable retention of moisture, fat and minerals (as ash) in W samples after cooking. CL was highest (P<0.05) in M sample and lowest (P<0.05) in W samples. Microwaved restructured steaks had higher (P<0.05) kramer shear force (KSF) and bind strength (BS), while pan-fried and conventionally oven cooked steaks had lower (P<0.05) KSF. The thiobarbituric acid-reactive substances (TBARS) content was low in all restructured steaks but was affected by both cooking and formulation. Although cooking can change the proximal composition of steaks, lipid retention (>90%) was greatest in the case of the W sample, thus assuring that the ultimate objective of these restructured meats, namely to provide a source of walnut and walnut fat, would be successful. PMID- 22061783 TI - Development of a modified dry curing process for beef. AB - The development of a dry curing process using physical treatments to promote the diffusion of the cure ingredients was studied. Vacuum pulsing with and without tumbling, continuous vacuum, and tumbling only treatments were compared with a conventional static dry cure control method on beef M. supraspinatus. Vacuum tumble and tumble only treatments gave highest core salt content after 7 days conditioning (3.3% and 3.1%, respectively). All test treatments resulted in higher colour uniformity and lower % cook loss in comparison to control (P<0.001). The control and vacuum pulsed samples were tougher (P<0.001). Vacuum tumble and tumble only treatments gave higher acceptability (P<0.001). Based on these findings for M. supraspinatus, indicating that the vacuum tumble treatments gave the best results, further testing of this method was conducted using the M. biceps femoris in addition to the M. supraspinatus. Cured beef slices were stored in modified atmosphere packs (MAP) (80%N(2):20%CO(2)) for up to 28 day at 4 degrees C. Redness (a(*), P<0.001) decreased over storage time in M. biceps femoris. Vacuum tumble treatment increased (P<0.05) redness in M. supraspinatus. Results obtained demonstrate the benefits of vacuum tumbling over the other physical treatments as a method for accelerating the dry curing process, producing dry cured beef products with enhanced organoleptic quality and increased yields. PMID- 22061784 TI - Preference and juiciness of Iberian dry-cured loin as affected by intramuscular fat content, crossbreeding and rearing system. AB - Preference ranking tests for juiciness and overall liking of dry cured loins from Iberian pigs with different genetic backgrounds (pure Iberian or crossbred Iberian*Duroc pigs), reared under different productive systems (outdoors on acorns and grass or indoors with mixed diets) and with different intramuscular fat (IMF) content, were conducted. IMF showed a positive influence on preference for juiciness and liking in subjects over 25 years of age, while younger consumers showed a similar trend for juiciness but not for preference. Loins from pure Iberian pigs showed significantly better ranking for juiciness and overall liking than those from crossbred pigs, even when the IMF content was similar. Dry cured loins from pigs reared outdoors and fed on acorns and pasture were ranked significantly better than those from animals fed indoors on concentrates, even though the mixed diets used were enriched in monounsaturated fatty acids and vitamin E in order to obtain meat with similar features to that of pigs reared outdoors, and despite very similar IMF contents. In conclusion, dry cured loins with high IMF content, from pure Iberian pigs and reared outdoors on acorns and grass attain the highest consumer preference. PMID- 22061785 TI - Breaking strength of dry fermented sausages and their correlation with texture profile analysis (TPA) and physico-chemical characteristics. AB - In order to assess its usefulness for monitoring textural properties of dry fermented sausages (chorizo, salchichon, salami, fuet and mini-fuet) the determination of breaking strength (BS) was evaluated. Texture profile analysis (TPA) and physico-chemical measurements (pH, aw, dry matter, fat content) were also performed. The BS determined by tensile test and TPA analysis produced complementary information that allowed these meat products to be grouped according to four different textural profiles. These profiles were characterized (p<0.05) by the values of BS, hardness, adhesiveness, cohesiveness and springiness. Multivariate analysis confirmed that BS and TPA parameters were correlated significantly (p<0.00005). On basis of these results, TPA parameters could be used to construct regression models to predict BS and therefore, to obtain a more complete textural property description of the dry fermented sausages. The resulting regression model was BS=-0.777+0.728*adhesiveness 16881*cohesiveness+1884.61*springiness+0.042*hardness (R(2)=0.634, p<0.00005). PMID- 22061786 TI - The crossbreeding of different Duroc lines with the Iberian pig affects colour and oxidative stability of meat during storage. AB - Colour and oxidative stability of Longissimus dorsi (LD) and Biceps femoris (BF) muscles from 3 different Iberian*Duroc genotypes (GEN1: ? Iberian*? Duroc1, GEN2: ? Duroc1*? Iberian; GEN3: ? Duroc2*? Iberian) were analysed during 10days of refrigerated storage. GEN1 and GEN2 are reciprocal crosses, while the difference between GEN2 and GEN3 is the Duroc sire line. The genotype Duroc1 was selected for the manufacture of dry-cured-meat products while the genotype Duroc2 was selected for meat production. BF showed more intense colour and oxidative changes during storage than LD, which is in accordance with their different metabolic pattern, since BF is an intermediate oxidative muscle whereas LD is a glycolytic one. Important differences were found between crosses due to the genotype of the Duroc sire line; however, reciprocal crosses (GEN1 and GEN2) showed a similar pattern. The lowest post-mortem pH of GEN3 could be a deciding factor of the oxidative and colour stability during storage as GEN3 had higher drip and cook loss as well as higher susceptibility to iron-ascorbate-induced oxidation. In addition, chops from GEN3 were paler (lower L(*)) and showed a higher discolouration (higher decrease of a(*)) besides higher lipid (TBA-RS) and protein oxidation (carbonyl content) after the storage. PMID- 22061787 TI - Modeling and predicting spoilage of cooked, cured meat products by multivariate analysis. AB - A cooked, cured meat product is a perishable product spoiled mainly by lactic acid bacteria (LAB). LAB cause discoloration, slime formation, off-odors and off flavors as the result of their metabolic activity producing various products. These microbial products in conjunction with the microbial population could be used to assess the degree of spoilage of this type of product. The spoilage evaluation was achieved by following a multivariate approach. Cluster analysis, principal component analysis and partial least square regression were employed to associate spoilage with microbiological and physicochemical parameters. The developed model was capable of giving accurate predictions of spoilage describing the spoilage associations. The study might contribute to the improvement of quality assurance systems of meat enterprises. PMID- 22061788 TI - National beef tenderness survey - 2006: Assessment of Warner-Bratzler shear and sensory panel ratings for beef from US retail and foodservice establishments. AB - Beef from retail and foodservice establishments in 11 US cities was evaluated using Warner-Bratzler shear (WBS) and consumer evaluation panels. Postmortem aging times ranged from 3 to 83d for retail and 7 to 136d for foodservice with mean aging times of 22.6d and 30.1d, respectively. For retail, the three cuts from the round - top round, bottom round, and eye of round - had the highest (P<0.05) WBS values compared to cuts from the chuck, rib, and loin. Top loin steaks had the lowest (P<0.05) WBS value compared to ribeye and top sirloin foodservice steaks. Retail bone-in top loin, top loin, ribeye, T-bone, and porterhouse received the highest (P<0.05) ratings by consumers for overall like and like tenderness. Quality grade had little or no effect on foodservice sensory evaluations. Improvements in round tenderness are needed to increase consumer acceptability. PMID- 22061789 TI - Biogenic amine production in Spanish dry-cured "chorizo" sausage treated with high-pressure and kept in chilled storage. AB - Biogenic amine formation and microbiota evolution were assessed in Spanish dry cured "chorizo" sausage treated with high-pressure (HP) and kept at 2 degrees C. High-pressures did not affect (p<0.05) pH or water activity (a(w)). However, HP treatment did significantly reduce the level of lactic acid bacteria, by <1 logarithmic unit. Microorganism levels remained low throughout storage and the only significant reduction was in the HP treated lot at 160 days. The HP treatment caused a reduction (p<0.05) of tyramine, putrescine, and cadaverine levels, while there was a significant increase in spermidine. Amine levels increased (p<0.05) in the course of storage, although unrelated to increased microorganism levels, possibly because decarboxylase activity continued in the substrate during storage. HP seems to be effective for reducing the formation of biogenic amines in this kind of product. PMID- 22061790 TI - Variation in the response to manipulation of post-mortem glycolysis in beef muscles by low-voltage electrical stimulation and conditioning temperature. AB - The aim of this study was to investigate how manipulation of glycolytic rate by post-mortem processing conditions influences quality of aged beef of two bovine muscles of different physiological character, longissimus dorsi (LD) and adductor (AD). Post-mortem glycolysis was manipulated by low-voltage electrical stimulation (LV-ES) of half carcasses and by chilling rate of the muscles. Multivariate statistical analysis was used to visualise the data, while ANOVA was used to identify significant effects and interactions. As expected there was a significant effect of LV-ES on the pH decline in the first hours post-mortem in both muscles. Moreover, significant effects of LV-ES on WB shear force measured 2 and 8 days after slaughter were observed for LD at both chilling temperatures, while for AD no effect on WB shear force was observed. Furthermore, the results revealed a large individual variation in the response of LV-ES on both pH decline and WB shear force, and this variation did not always correlate for the two responses. Some animals showed no response of LV-ES on pH decline, but still had an improved WB shear force, and vice versa. The results from this study indicate that there probably are other mechanisms than accelerated pH decline and prevention of cold-shortening, by which LV-ES can affect meat tenderness. PMID- 22061791 TI - Sex determination in beef by melting curve analysis of PCR amplicons from the amelogenin locus. AB - Sex determination of beef is important to meet the rules of the Commission Regulation (EC) 765/2002 that qualify for export refunds. A SYBR Green sex identification assay based on melting curve analysis of PCR amplicons from the amelogenin locus (AMELX and AMELY) was developed. The PCR amplicons of 130/130 and 130/67 base pairs produced from female and male beef, respectively, are easily distinguished by both melting curve analysis and gel electrophoresis. Results from the melting curve analysis of amplicons are ready in less than three minutes, and requires no additional work in addition to the PCR setup. Applicability of the sex determination assay was studied by analysis of 12 unknown beef samples and the results were compared to an accredited method based on gel electrophoresis. In addition, six different cattle breeds were examined. All test results were correct in respect to sex. PMID- 22061792 TI - Protease activity higher in postmortem water buffalo meat than Brahman beef. AB - We previously demonstrated that postmortem water buffalo meat had higher tenderness than Brahman beef. In order to explain this difference in tenderness, the objective of the current study was to investigate the protease activity in these two meats. Five female crossbred water buffalo (Philippine Carabao*Bulgarian Murrah) and five female crossbred cattle (Brahman*Philippine Native) were slaughtered at 30months of age, followed by immediate sampling of Longissimus thoracis muscle for measurement of protease activity. Results showed that buffalo meat had significantly higher protease activity compared to beef (P<0.05). Furthermore, calpain inhibitor 1, a specific inhibitor of calpains 1 and 2, was the most effective inhibitor of protease activity. There was no difference in calpastatin activity, and no major differences were observed in calpains 1, 2, and calpastatin expression by Western blotting. This study suggests that higher calpain activity in early postmortem buffalo meat was responsible for the increased tenderness of water buffalo meat compared to beef. PMID- 22061793 TI - Relationships between carcass quality parameters and genetic types. AB - It is important for the meat industry, including pig farmers and breeding companies, to know the composition of the carcass including the proportions of the different commercial cuts when making decisions on the type of pigs to be produced and marketed. Carcass composition is influenced significantly by the genotype of the animals. The aim of this work was to characterise carcasses from five different pig genotypes, by means of the quantification and comparison of their physical composition. Carcasses from 500 gilts from five different genetic types were studied. These lines were based on the following breeds: Large White, Landrace, Duroc, Pietrain and a Meishan synthetic population developed from a cross with a Large White based line. Measurements were taken in the carcasses directly with a ruler and with the Fat-O-Meat'er. The carcasses were cut following the European reference method and the four main joints were dissected. Carcasses from the Pietrain based line, which was halothane negative, presented the highest killing-out (83.34%) and were the shortest (81.81cm). The Pietrain based line was also the leanest and the Meishan based line the fattest. The highest proportion of ham (270.9g/kg) and the lowest proportion of belly (97.97g/kg) were found in the Pietrain line. The proportion of lean in all of the dissected cuts was higher in carcasses from this line while the Meishan line presented the highest proportions of intermuscular fat in all of the pieces. Carcasses came from the Pietrain line received the highest conformation scores and they were leaner and with better ham yield. PMID- 22061794 TI - Production of salami from beef, horse, mutton, Blesbok (Damaliscus dorcas phillipsi) and Springbok (Antidorcas marsupialis) with bacteriocinogenic strains of Lactobacillus plantarum and Lactobacillus curvatus. AB - Lactobacillus plantarum 423, producer of bacteriocin 423, Lactobacillus curvatus DF38, producer of curvacin DF38, and a bacteriocin-negative mutant of L. plantarum 423 (423m) were evaluated as starter cultures in the production of salami from beef, horse, mutton, Blesbok (Damaliscus dorcas phillipsi) and Springbok (Antidorcas marsupialis). Growth of L. plantarum 423 and L. curvatus DF38 was best supported in Blesbok salami, as revealed by the highest growth rate during sweating, cold smoking and maturation, and final cell numbers after 70 days (1*10(8) and 5*10(7)cfu/g, respectively). Growth of Listeria innocua was the best suppressed in Blesbok salami fermented with L. plantarum 423 and L. curvatus DF38. Growth of L. innocua in horse salami was best suppressed when fermented with L. curvatus DF38. The final pH of salami fermented with L. plantarum 423 and L. plantarum 423m was slightly lower (4.4) compared to the pH of salami produced with L. curvatus DF38 (pH 4.7). No significant differences (P>0.05) were recorded by a trained sensory taste panel amongst the three starter cultures regarding colour and venison like aroma. Horse, Blesbok and Springbok salami were rated significantly higher (P?0.05) in salami flavour than mutton salami, which was rated the lowest for this attribute. Blesbok salami was rated the highest for sour meat aroma, while beef salami was rated the lowest. Springbok salami was rated the highest in terms of oily mouth feel. Beef salami had the most compact structure and horse salami the softest structure of all meat types fermented. In general, salami produced with L. plantarum 423 yielded the best sour meat aroma, colour, texture, venison like flavour, sour meat flavour and oily mouthfeel and is considered superior to the L. plantarum mutant (strain 423m) and L. curvatus DF38. PMID- 22061795 TI - Investigation of the microbial ecology of Ciauscolo, a traditional Italian salami, by culture-dependent techniques and PCR-DGGE. AB - The microbial ecology of 22 samples of commercially available Ciauscolo salami were investigated using a polyphasic approach, based on culture-dependent and independent techniques. The viable counts of pathogen and hygiene indicator microorganisms highlighted the adequate application of good manufacturing practices, while the viable counts of the lactic acid bacteria, coagulase negative cocci, and yeasts showed dominance of the first of these microbial groups. Bacterial and fungal DNA were extracted directly from the salami and amplified by PCR, using two primer sets targeting the 16S and 28S rRNA genes, respectively. Denaturing gradient gel electrophoresis (DGGE) and sequencing of selected bands were used to investigate the microbial ecology of these Ciauscolo salami. The most frequently found bacterial species were Lactobacillus sakei and Lb. curvatus, while Debaryomyces hansenii was the prevalent yeast species detected. Cluster analysis of the DGGE profiles and calculation of biodiversity indices allowed the degree of microbial similarity across these salami to be determined. PMID- 22061796 TI - Effects of starter cultures and nitrite levels on formation of biogenic amines in sucuk. AB - The effects of starter cultures, starter A (Lactobacillus sakei+Staphylococcus carnosus) and starter B (Pediococcus acidilactici+Staphylococcus xylosus+Lactobacillus curvatus), nitrite levels (0, 75, and 150ppm) and ripening period on biogenic amine production were investigated in sucuk (Turkish dry fermented sausage) production. Changes in biogenic amines, pH, water activity, moisture, non-protein nitrogen, nitrite and counts of lactic acid bacteria, Micrococcus/Staphylococcus, Enterobacteriaceae, and moulds-yeasts were determined. Ripening period had a very significant effect (P<0.01) on the all biogenic amines. Sausages produced by fermentation with starter cultures, as compared to natural fermentation (control), had lower amounts of putrescine, cadaverine and tyramine (P<0.05). Starter cultures A and B were found to have almost the same effect on the formation of biogenic amines. Use of nitrite in sucuk production affected the formation of biogenic amines except for spermidine and spermine (P<0.01). Lactic acid bacteria counts in the control group were lower than that of starter culture groups. Lactic acid bacteria, Micrococcus/Staphylococcus, and moulds-yeasts counts increased during ripening period while levels of species of Enterobacteriaceae decreased, which was also found to be under the detectable level (<100cfug(-1)), by day 3 of ripening. PMID- 22061797 TI - Effect of information about animal welfare, expressed in terms of rearing conditions, on lamb acceptability. AB - The present study was aimed to assess the effect of information about the farming system and welfare of artificially (AR) and ewe-reared lambs (ER) on meat acceptability. An 84-consumer panel was asked to give three types of evaluation for both products: tasting without information (perceived liking); information without tasting (expected liking); tasting with information (actual liking). For both products, the expected liking was significantly different from the perceived liking (P<0.001), thus indicating that a disconfirmation occurred. The consumers found ER meat worse than expected (negative disconfirmation) and AR meat better than expected (positive disconfirmation). No significant difference between perceived and actual liking was observed for ER lamb (P>0.05), whereas, for the meat produced by AR lambs actual liking was lower than perceived liking (P<0.001). However, consumers did not completely assimilate their liking in the direction of expectations, as indicated by the fact that expectancy for AR lamb was significantly lower than actual acceptability (P<0.001). Mean scores of perceived liking were higher for the meat produced by AR animals as compared to ER lambs (P<0.05). Conversely, expected and actual liking scores were higher for meat from ER lambs than for meat from AR animals (P<0.001 and P<0.05, respectively). These results show that information about animal welfare, expressed in terms of rearing conditions, can be a major determinant of animal based food acceptability, thus providing a potential tool for meat differentiation. PMID- 22061798 TI - Long-term effects of neonatal stress on adult conditioned place preference (CPP) and hippocampal neurogenesis. AB - Critically ill preterm infants are often exposed to stressors that may affect neurodevelopment and behavior. We reported that exposure of neonatal mice to stressors or morphine produced impairment of adult morphine-rewarded conditioned place preference (CPP) and altered hippocampal gene expression. We now further this line of inquiry by examining both short- and long-term effects of neonatal stress and morphine treatment. Neonatal C57BL/6 mice were treated twice daily from postnatal day (P) 5 to P9 using different combinations of factors. Subsets received saline or morphine injections (2mg/kgs.c.) or were exposed to our neonatal stress protocol (maternal separation 8h/d * 5d+gavage feedings +/- hypoxia/hyperoxia). Short-term measures examined on P9 were neuronal fluorojade B and bromodeoxyuridine staining, along with urine corticosterone concentrations. Long-term measures examined in adult mice (>P60) included CPP learning to cocaine reward (+/- the kappa opioid receptor (KOR) agonist U50,488 injection), and adult hippocampal neurogenesis (PCNA immunolabeling). Neonatal stress (but not morphine) decreased the cocaine-CPP response and this effect was reversed by KOR stimulation. Both neonatal stress or morphine treatment increased hippocampal neurogenesis in adult mice. We conclude that reduced learning and increased hippocampal neurogenesis are both indicators that neonatal stress desensitized mice and reduced their arousal and stress responsiveness during adult CPP testing. Reconciled with other findings, these data collectively support the stress inoculation hypothesis whereby early life stressors prepare animals to tolerate future stress. PMID- 22061799 TI - Dissociable roles of the medial prefrontal cortex, the anterior cingulate cortex, and the hippocampus in behavioural flexibility revealed by serial reversal of three-choice discrimination in rats. AB - Contributions of different limbic cortical areas to mediation of behavioural flexibility were examined using repeated acquisition of three-choice discrimination in operant chambers. Rats were trained on a series of positional discrimination tasks with three levers, where position of the correct lever remained the same within a task but shifted across tasks. Ibotenic acid lesions of the medial prefrontal cortex impaired acquisition of each discrimination task by increasing errors specifically in the early phase of each task. These errors were characterised by perseveration to the previously correct lever. By contrast, lesions of the anterior cingulate cortex resulted in the impairment of discrimination in general without inducing perseveration; the impairment was instead characterised by disruption of general error-correction processes. Hippocampal lesions severely impaired learning by increasing perseverative tendencies that were present throughout the learning stages in each task. These results extend our understanding of the contributions of the different nodes of the limbic cortico-striatal circuit to different aspects of behavioural flexibility. PMID- 22061800 TI - Dexamethasone and Abeta25-35 accelerate learning and memory impairments due to elevate amyloid precursor protein expression and neuronal apoptosis in 12-month male rats. AB - Alzheimer's disease (AD) is an irreversible, progressive brain disorder of the elderly characterized by learning and memory impairment. Stress level glucocorticoids (GCs) and beta-amyloid (Abeta) peptides deposition are found to be correlated with dementia progression in patients with AD. However, little is known about the simultaneous effects of glucocorticoids and Abeta on learning and memory impairment and its mechanism. In this study, 12-month-old male rats were chronically treated with Abeta(25-35) (10 MUg/rat, hippocampal CA1 injection) and dexamethasone (DEX, 1.5mg/kg) for 14 days to investigate the effects of DEX and Abeta(25-35) treatment on learning and memory impairments, pathological changes, neuronal ultrastructure, amyloid precursor protein (APP) processing and neuronal cell apoptosis. Our results showed that DEX or Abeta(25-35) treatment alone for 14 days had caused slight damage on learning and memory impairments and hippocampal neurons, but damages were significantly increased with DEX+Abeta(25 35) treatment. And the mRNA levels of the APP, beta-secretase and caspase 3 were significantly increased after DEX+Abeta(25-35) treatment. The immunohistochemistry demonstrated that APP, Abeta(1-40), caspase 3 and cytochrome c in hippocampus CA1 were significantly increased. Furthermore, Hoechst 33258 staining and Abeta(1-40) ELISA results showed that DEX+Abeta(25-35) treatment induced hippocampus CA1 neuron apoptosis and increased the level of Abeta(1-40). The results suggest that the simultaneous effects of GCs and Abeta may have important roles in the etiopathogenesis of AD, and demonstrate that stressful life events and GC therapy may increase the toxicity of Abeta and have cumulative impacts on the course of AD development and progression. PMID- 22061801 TI - Antidepressive and anxiolytic activity of selective estrogen receptor modulators in ovariectomized mice submitted to chronic unpredictable stress. AB - Estradiol has antidepressive and anxiolytic actions. However, its therapeutic use is limited by its peripheral effects. Selective estrogen receptor modulators may represent an alternative to estradiol for the treatment of depressive symptoms. Here we report that tamoxifen and raloxifene decrease immobility time in the forced swim test and increases the time spent in open arms in the elevated plus maze in ovariectomized mice submitted to chronic unpredictable stress. PMID- 22061802 TI - Use of irradiation to control foodborne pathogens and extend the refrigerated market life of rabbit meat. AB - This study set out to evaluate the microbiological status of rabbit meat and the possibility of using irradiation to control foodborne pathogenic bacteria and extend the refrigerated storage life of meat. Rabbit meat samples were gamma irradiated at doses of 0, 1.5 and 3 kGy. The samples were stored at refrigeration temperature, then the effects of irradiation and storage on their microbiological, chemical and sensory properties were studied. Irradiation at 1.5 kGy significantly reduced the counts of Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis and enterobacteriaceae but was not enough for complete elimination of Salmonella. However, 3 kGy dose reduced the counts of S. aureus, L. monocytogenes, E. faecalis and enterobacteriaceae by more than 3, 3, 1.4 and 4 log units, respectively, while Salmonella was not detected. On the other hand, irradiation at 1.5 and 3 kGy significantly reduced the counts of aerobic mesophilic bacteria, psychrophilic bacteria and molds and yeasts and prolonged the refrigerated shelf-life of samples to 12 and 21 days, respectively, compared to 6 days for non-irradiated controls. Irradiation of samples significantly increased their amounts of thiobarbituric acid reactive substances (TBARS) but had no significant effects on their total volatile nitrogen (TVN) contents, while storage significantly increased the TBARS and TVN for irradiated and non-irradiated samples. gamma irradiation showed no significant effects on the sensory properties of raw meat. Moreover, fried burgers prepared from irradiated rabbit meat showed high sensory acceptability similar to those prepared from non-irradiated meat. PMID- 22061803 TI - Characterisation of a lard cured with spices and aromatic herbs. AB - The study considered the proximate composition, pH, free acidity, MDA and peroxide values of a cured and ripened lard covered with spices and aromatic herbs, these latter parameters, due to lipolytic endoenzymatic phenomena, tended to increase until the end of the salting period. Throughout the production phases the bacterial load was very low. The final vacuum-packed product had a shelf-life of about 90 days and its fatty acid and cholesterol composition was typical of lard. A GC/MS study of the spices/herbs in the lard highlighted which components came from the spices/aromatic herbs and which came from phenomena due to lipolytic endoenzymatic processes. PMID- 22061804 TI - Effect of a commercial freeze/tempering process on the viability of Cryptosporidium parvum oocysts on lean and fat beef trimmings. AB - Lean and fat beef trimmings (25 cm(-2)) were inoculated with approximately 250,000 Cryptosporidium parvum oocysts, placed in commercial packages (28 kg boxes) and subjected to normal commercial processes i.e. blast frozen (to -20 degrees C within 60 h), stored (-20 degrees C, 21 days), tempered (48 h at -3 degrees C), and held at 0 degrees C for 10 h. Inoculated areas were then excised, pulsified (30 s in 50 ml PBST), and centrifuged (2500*g, 15 min). The resultant pellet was resuspended in 10 ml water and subjected to immunomagnetic separation and viability dye assay. Following the commercial freeze/tempering process the viability of the oocysts had decreased from 90.6% viable in the working stock suspension to 7.17% and 9.46% viable on lean and fat trimmings, respectively. The results of this study indicate that if C. parvum oocysts were present on beef trimmings their viability would be substantially reduced as a result of the freeze/tempering process. PMID- 22061805 TI - Gastrointestinal outbreaks associated with fermented meats. AB - Fermented meats, including salami, various types of fermented sauages and snack sticks have seen a revival in their popularity in recent years. The production of such foodstuffs generally lies in traditional techniques, however, both the quality and in particular the safety of such products intrinsically rests with the microbiology of the fermentation processes. Simultaneously, there has been increased concern over the safety of such products following the increased incidence of outbreaks of Salmonella and verocytotoxigenic Escherichia coli food poisoning related to these products. This update reviews the prevalence of fermented meat associated food-poisoning outbreaks (n=13) and the proposed microbiological specifications used to assess the safety of such foodstuffs. PMID- 22061806 TI - Relationships between skatole and androstenone accumulation, and cytochrome P4502E1 expression in Meishan*Large White pigs. AB - The effects of age, castration and diet on accumulation of skatole and androstenone in the backfat of 50% Meishan male pigs, was studied in relation to boar taint. Skatole and androstenone deposition in backfat of entire males was increased with age (114, 144 and 174 days). Castration significantly decreased skatole and androstenone levels in all age groups. The level of cytochrome P4502E1, the initial enzyme involved in hepatic skatole metabolism, was increased by castration at all ages. These results suggest that the decrease in androstenone levels following castration affects the regulation of cytochrome P4502E1 expression, and as a consequence, results in a decrease in skatole levels. The use of sugar beet feed in the diet decreased the level of skatole and increased that of cytochrome P4502E1 expression, but did not affect androstenone levels. It is suggested that skatole accumulation is reduced both by castration and by diet via induction of cytochrome P4502E1. However, the mechanism of induction of cytochrome P4502E1 by diet is different from that involved in its induction by castration. PMID- 22061807 TI - Effects of body weight and sex on carcass tissue distribution in goats. AB - Distribution of fat, muscle and bone tissues was studied in bucks, wethers and doe Jebel Akhdar (JA) Omani goats raised under intensive management and slaughtered at 11, 18 or 28 kg body weight (BW). Weight of individual tissues was expressed as percentage of total respective tissue weight in the half carcass. Weight of total body fat in the empty body weight (EBW) ranged between 7.6% in bucks at 11 kg BW and 23.5% in does at 28 kg BW. At 18 kg BW, JA goats had higher TBF, carcass and non-carcass fat than those slaughtered at 12 kg BW (P<0.001). Does and wethers had a faster rate of deposition of carcass and non-carcass fat relative to EBW. Therefore, they had higher fat content (P<0.001) than bucks at 28 kg BW. The highest proportion of fat in the body was deposited intermusculary whereas the omentum constituted the highest non-carcass fat proportion. About 55% of the musculature in JA goat carcasses was found in muscle groups of the proximal hind leg, around the vertebral column and in the proximal forelimb (expensive muscle groups). Bucks had higher proportions of musculature in the forequarter (P<0.001) and intrinsic muscles of the neck but lower proportions of muscles at the proximal hind limb (P<0.001) than does and wethers. About 51% of the total skeleton was found in the axial skeleton, 22-23% in the forelimb and 22 23% in the hind limb of JA goats. There were few sex or slaughter weight effects on proportions of bone weight in the skeleton. In general, slaughter weight and sex effects on tissue distribution were more pronounced in the fat tissue. The magnitude of these effects on muscle and bone tissues was small and is unlikely to have economic impact on meat production from goats. PMID- 22061808 TI - The buffering capacity of porcine muscles. AB - The aim of this study was to investigate the buffering capacity (BC) of five porcine muscles. The pH of muscles with zero lactate was also estimated. The BC was calculated on the basis of the amount of lactate accumulating in the muscle between two sampling times and the simultaneous pH decline. Two muscle samples were obtained from each muscle (n=13-36): one as soon as possible after slaughter and the other 24 h post-mortem. The BCs (mmol lactate/(pHkg)) were in the light gluteus superficialis, longissimus dorsi and semimembranosus muscles 48.3+/-8.8, 48.6+/-9.2 and 46.8+/-13.0, and in the dark infraspinatus and masseter muscles 45.3+/-13.1 and 32.0+/-11.5, respectively. The dark masseter muscle differed significantly from the other muscles studied (p<0.01). The estimated pH values of muscles with zero lactate were in the gluteus, longissimus dorsi, semimembranosus muscles 7.14+/-0.06; 7.18+/-0.06; 7.38+/-0.08, and in the infraspinatus and masseter muscles 6.87+/-0.07; 7.03+/-0.08, respectively. It was suggested since lactate is continuously formed in the muscles, the resting pH of living light and dark muscles may, however, be the same. The approach used in this study to determine the BC resulted in values which are close to values previously reported in the literature (measured by using titration curves). PMID- 22061809 TI - Carcass and meat quality of light lambs using principal component analysis. AB - Eighty-six male light lambs of Manchego breed were used in this study. Principal component (PC) analysis was performed to study the relationship between carcass quality variables (n=22) and between meat quality measures (n=21). The carcass quality was assessed using objective and subjective measurements of conformation and fatness besides the joints proportion and tissues proportion of the leg. The measurements used to evaluate meat quality were pH in longissimus dorsi and semitendinosus muscles, the colour, moisture, water holding capacity, cooking losses, texture and sensorial analysis on longissimus dorsi. The five first PCs explained about 77% of the total variability for carcass measures whereas for meat quality the 74% of the total variability was explained for the eight first PCs. All the carcass measurements showed similar weight to define the first PC, whereas the muscle and bone proportion as well as muscle:bone ratio of the leg were useful to define the second PC. The meat quality measures that were more effective to define the first PC were the meat colour measurements, whereas the sensorial variables defined the second PC. The projection of the carcass quality data in the first two PCs allowed to distinguish clearly between heavier carcasses (higher than 6.5 kg) and lighter carcasses (lower than 5.5 kg). The carcasses with a weight higher than 6.5 kg were on the left side of the figure, where the variables of conformation and fatness lie. The group of medium carcass weight were placed between the two previous groups. The projection of the meat quality data in the first two PCs did not differ between hot carcass weights, although there was a trend, the lighter carcasses lay on the left side of the graph, which implies small differences between meat quality in this range of carcass weight. PMID- 22061810 TI - Effect of starter culture, spice mix and storage time and temperature on biogenic amine content of dry fermented sausages. AB - Two types of dry fermented sausage differing in spicing mixture and the diameter (low content of red pepper+diameter 80 mm, H-sausage; high content of red pepper+diameter 55 mm, P-sausage, respectively) were produced in parallel with two different starter cultures (Pediococcus pentosaceus+Staphylococcus carnosus, B-samples and S. carnosus+Staphylococcus xylosus+Lactobacillus farciminis, F samples, respectively). The sausages were ripened 21 days and subsequently stored 91 days at the room temperature. Concentration of both most abundant amines, putrescine and tyramine (y; mg/kg DM) increased significantly (P<0.01) in HB sausage during ripening (x; days): y=2.5+18.13x-0.3144x(2) (R(2)=0.99) and y=0.7+8.17x-0.1130x(2) (R(2)=0.99), and also during storage: y=127.3+5.123x (R(2)=0.79) and y=26.0+3.211x (R(2)=0.74), respectively. At the end of ripening, putrescine (247 mg/kg DM) and tyramine (123 mg/kg DM) content in the HB-sausage was higher (P<0.05) than in the PB-sausage (12 and 9 mg/kg DM, respectively), concentration of either of these amines was negligible (1 mg/kg DM) in either type of F-inoculated sausage. Both starter culture and sausage type influenced significantly (P<0.001) both putrescine and tyramine content in the sausage; starter accounted for 57% and 55% of total variability in putrescine and tyramine content, respectively. Due to the significant (P<0.05) increase of total aerobic counts in the HB-sausage between the end of ripening and the 7th day of storage, followed by the significant (P<0.01) increase of the sum of total biogenic amines between the end of ripening (425 mg/kg DM) and the end of storage (1029 mg/kg DM), the storage of the dry fermented sausages at the room temperature should not be recommended. PMID- 22061811 TI - Effect of selection for growth rate on biochemical, quality and texture characteristics of meat from rabbits. AB - Biochemical characteristics, including myosin heavy chain I (MHC-I) percentage, isocitrate dehydrogenase and aldolase activities, meat quality traits and instrumental texture properties of rabbits selected for different growth rates were studied. The animals of the control (C) group (7th generation; n=60) were raised in parallel with those of selection (S) group (21st generation; n=60). Carcass weights (1230.1+/-19.8 and 1348.3+/-20.1 g, for C and S, respectively) and perirenal and scapular fat content differed significantly (P<0.01) between the two groups. Water holding capacity was expressed as the percentage of pressure released water and was significantly different (P<0.05) between groups C and S (33.29% and 35.57%). MHC-I percentage and aldolase activity also differed significantly (P<0.05) between groups, group C showing higher oxidative traits than group S (MHC-I: 12.5% and 9.8%; aldolase: 597.11 and 636.83 UI/g muscle). Texture properties from the Warner-Bratzler test showed higher (P<0.001) shear firmness for loin in the S group (1.69 kg/s cm(2)) than in the C group (1.34 kg/s cm(2)). In addition, the texture profile analysis indicated that chewiness, gumminess and hardness were also higher in the S group (P<0.01). In conclusion, the results confirmed a positive effect of the selection on productive traits and a negative effect on instrumental texture properties and on the water holding capacity of the meat. PMID- 22061812 TI - Relationship between pH before salting and dry-cured ham quality. AB - The effect of pH before salting on pork quality was studied in two sets of experiments: 904 hams, set A; and 104 hams, set B; the latter was used to verify the results from A. After pH measurements, the hams were subjected to the traditional process for producing Spanish dry-cured ham and then evaluated by an expert panel to correlate the sensory characteristics to the pH measurement before salting. The parameters evaluated were pastiness, softness, anomalous cut colour, crusting and white spots. Moisture, non-protein nitrogen, salt, protein, nitrate and nitrite were determined in samples from both experiments. The results obtained in experiment A showed that pastiness is closely related to the pH before salting (p<0.001), but not softness. From the receiver operating characteristics curve, a cut-off point of pH of 5.55 was selected to classify the raw material in two groups: normal-pH and low-pH hams. The pH before salting can also be correlated with the appearance of anomalous cut colour and crusting in hams. White spots were absent in both pH groups. Regarding compositional parameters, there were significant differences in moisture (p<0.001), salt (p<0.001), protein (p<0.001), non-protein nitrogen (p<0.001) and nitrate (p<0.05) contents between low-pH and normal-pH hams. The results from experiment B, confirmed the relationship between pH before salting and the appearance of defective texture and colour in the final product. Also results from experiment B confirmed the compositional parameters found in experiment A. Thus, the pH before salting is a good predictor for meat quality allowing the classification of the raw material in the first stage of manufacture. After classification, some modifications to the processing can improve the final characteristics of dry cured hams. PMID- 22061813 TI - Evaluation of the physico-chemical, rheological and sensory characteristics of commercially available Frankfurters in Spain and consumer preferences. AB - The physico-chemical, rheological and sensory characteristics of different commercially available Frankfurters were studied. Samples presented values of A(w) and pH from 0.954 to 0.972 and 5.88 to 6.43, respectively. Greater differences were observed in parameters such as fat and salt content, with values ranging from 10.83% to 21.92% and 1.85% to 3.01%, respectively. With regard to total nitrogen, all samples presented values close to 2%. Free-choice profiling and generalised procrustes analysis of the sensory data permitted differentiation between samples and provided information about the attributes responsible for the observed differences. All the frankfurters scored in the moderate range for overall acceptability. Consumers identified reasons for purchasing frankfurters when evaluating the product's packaging. The most important criterion for consumers when purchasing frankfurters was the appetising aspect of the product in the packaging's illustration. PMID- 22061814 TI - Temperature abuse affects the quality of irradiated pork loins. AB - The influence of temperature abuse on the quality of irradiated pork loins was investigated. Pork loins were obtained directly from a local packing plant, sliced and vacuum-packaged. Pork loins were randomly separated into 3 groups, sliced, and assigned to receive 0, 1.5, or 2.5 kGy electron-beam irradiation. Then, each chop was further cut into three equal pieces and assigned to three temperature treatments: Trt I was placed in a refrigerator directly after irradiation; Trt II was left at room temperature for 3 h before refrigeration; and Trt III was exposed at room temperature for 1 h three consecutive days with intermittent storage at 4 degrees C between exposures. Before irradiation, each loin pieces were vacuum-packaged. Color, 2-thiobarbituric acid reactive substances (TBARS), and volatiles were measured after 0, 14, 28 and 42 days of storage, and water-holding capacity and sensory characteristics of the loins were measured after 0, 14 and 28 days of storage. Temperature abuse had no significant effect on color, oxidation, and volatiles of irradiated pork loins. However, temperature abuse improved water-holding capacity of meat, which could be caused by the accelerated hydrolysis of muscle proteins at higher temperature. Irradiation increased redness, sulfur contents in volatiles and off-odor of pork loin. Off-odor and redness induced by irradiation sustained during storage. Among sulfur compounds, the content of dimethyl disulfide decreased gradually while the level of thiourea remained relatively constant. Irradiation also increased water loss, which might be related to the structural damage in membrane during irradiation. This study shows that temperature abuse has little effect on the quality of irradiated pork. PMID- 22061815 TI - Effects of breed, diet and muscle on fat deposition and eating quality in pigs. AB - A study in 192 entire male pigs examined the effects of breed, diet and muscle on growth, fatness, sensory traits and fatty acid composition. There were four breeds: two modern breeds, Duroc and Large White and two traditional breeds, Berkshire and Tamworth. The diets differed in energy:protein ratio, being conventional (C) and low protein (LP) diets, respectively. Muscles investigated were the 'white' longissimus dorsi (LD) and the 'red' psoas major (PS). Breed influenced growth rate and fatness, the modern breeds being faster-growing with leaner carcasses. However, the concentrations of neutral lipid fatty acids and marbling fat (neutral lipid+phosopholipid fatty acids) were higher in Berkshire and Duroc, in both LD and PS. Relationships between marbling fat and P2 fat thickness showed clear breed effects, with Duroc having high marbling fat at low P2 and Tamworth low marbling fat at high P2. Breed effects on sensory scores given by the trained taste panel to griddled LD and PS steaks were relatively small. Breed affected the fatty acid composition of intramuscular neutral lipid, with high % values for the saturated fatty acids, 14:0 and 16:0 in Berkshire and Tamworth (fat carcasses) and high values for polyunsaturated fatty acids in Duroc and Large White (lean carcasses). Duroc had particularly high concentrations of the long-chain polyunsaturated fatty acids, 20:5n-3 and 22:6n-3 in phospholipid of both muscles. Diet influenced growth rate and fatness, the LP diet slowing growth and producing fatter meat, more so in the two modern breeds, and particularly in intramuscular rather than subcutaneous fat. This diet produced more tender and juicy meat, although pork flavour and flavour liking were reduced. The PS muscle had higher tenderness, juiciness, pork flavour, flavour liking and overall liking scores than LD. The concentration of phospholipid fatty acids was higher in PS than LD but neutral lipid fatty acid content and marbling fat were higher in LD. PMID- 22061816 TI - Quality characteristics of doner kebab made from sucuk dough which is a dry fermented Turkish sausage. AB - The objective of this study was to determine certain quality characteristics of the raw and cooked doner kebabs made from beef and sucuk dough which is a traditional fermented sausage. The doners were divided into two groups; traditional beef doners and sucuk dough groups, and all the samples were frozen and stored at (-30 +/-1 degrees C) for 60 days to monitor their quality characteristics. All of the raw and cooked doner samples were subjected to chemical and microbiological analysis while only the cooked doners were evaluated organoleptically at 0th, 30th and 60th days of storage. In the chemical analysis; proximate composition (% moisture, % protein, % fat, and % ash), pH and TBA values were determined. The samples were examined for total aerobic plate count (APC), total anaerobes, psychrotrophic bacteria, total coliforms, total staphylococcus/micrococcus count, mould and yeast to observe the hygienic quality of the doner samples. The results of chemical analysis, in general, showed that sucuk doners had higher ash content, pH and TBA values, and all of the doners had higher APC, psychrotrophic bacteria and coliform counts at the beginning compared to 30th and 60th days of storage not only in the raw condition but also in cooked counterparts. The sensory evaluation results indicated that sucuk doners received favorable preferences, therefore, traditional sausage (sucuk) dough application in doner production could be possible without posing any acceptability problems in terms of quality factors compared to traditional beef doners. PMID- 22061817 TI - Positional distribution of fatty acids in triacylglycerols from subcutaneous adipose tissue of pigs fed diets enriched with conjugated linoleic acid, corn oil, or beef tallow. AB - This study was conducted to determine the effects of dietary beef tallow, corn oil, and conjugated linoleic acid (CLA) on the distribution of fatty acids among positions within triacylglycerols. Crossbred barrows (n=6 per treatment group) received diets containing 1.5% beef tallow, 1.5% corn oil, or 1.5% CLA for 5 weeks. Subcutaneous adipose tissue samples were obtained immediately postmortem. The fatty acid composition was determined for the sn-2 positions of the triacylglycerols by digestion with Rhizopus arrhizus lipase. Fatty acids in the sn-1/3 position were calculated from these data. Feeding CLA increased (P<0.05) the concentration of total saturated fatty acids (SFA, especially 16:0) and isomers of CLA in adipose tissue lipids, but reduced (P<0.05) the concentration of total monounsaturated fatty acids (MUFA, especially 18:1n-9). Dietary CLA caused an accumulation of total SFA in the sn-1/3 position, with a proportional decrease in total MUFA and 18:2n-6 in the outer positions. Correspondingly, lipids extracted from CLA-fed pigs had slip points that were 10 degrees C higher (P<0.05) than those from corn oil- or tallow-fed pigs. These data suggest that dietary CLA increases the melting point of lipids in porcine adipose tissue by increasing the proportion of SFA at the sn-1/3 position of lipids. PMID- 22061818 TI - Evaluation of three 2-thiobarbituric acid methods for the measurement of lipid oxidation in various meats and meat products. AB - The aim of this work was to study the influence of different conditions on the 2 thiobarbituric acid (TBA) number, determined by the extraction and distillation method, as a measure of lipid oxidation in various meats and meat products. Different extracting agents (trichloroacetic acid and perchloric acid), different reaction times (20, 30, 40, 50 and 60 min) and the effect of sulfanilamide additions were evaluated. Significant differences with respect to reaction times were found. The best results were generally obtained with 40 min at 80+/-2 degrees C. Different values were found between samples with and without the addition of sulfanilamide. PMID- 22061819 TI - Proteome changes during pork meat ageing following use of two different pre slaughter handling procedures. AB - The influence of postmortem storage time and pre-slaughter conditions (transport the day before slaughter or immediately before slaughter) on proteome changes of pork meat was investigated over a 72 h ageing period. Intensities of 37 spots varied significantly (p<0.05) with ageing time. Changes indicated proteolysis of troponin T, actin, alpha-crystallin, myokinase, creatine kinase and mitochondrial ATPase, but also of proteins constitutive of the Z-lines, namely cypher proteins and myozenin. Other modifications were the intensity increase of a full-length protein of the sarcoplasmic reticulum, which may be linked to its increased extractibility after membrane disruption, and a gradual shift in pHi towards alkaline values of some forms of myosin light chains (MLC) 2 and 3. The pre slaughter conditions affected significantly (p<0.05) 8 spots. Mitochondrial ATPase was over-expressed in the group transported immediately before slaughter, also characterised by a faster pH fall, and the shift in pHi of MLC 2 was more pronounced. The pre-slaughter conditions had no significant effect on the above proteolytic events. PMID- 22061820 TI - Sodium chloride as a preferred protein extractant for pork lean meat. AB - The protein extractability of sodium chloride (NaCl), potassium chloride (KCl) and lithium chloride (LiCl) under a range of molarity with in the physiological pH range (pH 6.0-8.0) was assessed to determine the best protein extractant for pork lean meat. The individual proteins in the extracts were identified by electrophoresis. The highest protein extractabilities at pH 7.0 for NaCl, KCl and LiCl were observed at 1.2, 1.1, and 1.1 M, respectively. There was no significant difference in protein extractability for KCl and LiCl within physiological pH range. NaCl had a significant increase of its protein extractability as pH increased from 6.0 to 6.5 followed by a relatively constant extractability. The NaCl had the highest protein extractability followed by LiCl and KCl. The maximum number of proteins (26 bands) was found at the optimum concentration of each salt. However, resolution and clarity of bands were better in NaCl extracts. The pH variation does not affect the number and the intensity of the bands. PMID- 22061821 TI - The impact of homogenizer type and speed on the determination of myofibrillar fragmentation. AB - The myofibrillar fragmentation index (MFI) was determined by the turbidity method on five samples of ovine Longissimus muscle, aged for either 1 or 5 days and processed from the frozen state over 3 weeks. These samples were homogenized at one of four speeds (11,000, 16,000, 19,000 or 22,000 rpm) with a shaft type homogenizer (Ystral) and at 15,000 rpm with a blade type homogenizer (Omni mixer). At all speeds except 15,000 or 22,000 rpm samples were homogenized for either one or two bursts of 30 s giving a total of eight different treatments. There was a significant interaction between ageing and treatment (P<0.05) and ageing and muscle sample (P<0.001). Regarding the Omni mixer result as a reference standard, the closest result from the Ystral homogenizer was obtained at 19,000 rpm after two bursts of 30 s. These two treatments gave similar mean values for samples aged 5 days. Repeatability between duplicates did not differ significantly for the various treatments (r=0.55). A large difference was found between samples aged for 1 and 5 days and the difference was greater for the Ystral homogenizer than the Omni mixer. The Omni mixer values for 1 day aged samples were 38 units less than for samples aged for 5 days while this difference for the Ystral homogenizer was 63 units. As speed of homogenization increased with the Ystral homogenizer the overall mean values increased and the values were always greater after two bursts of 30 s compared to one burst of 30 s. The results suggest that the Ystral homogenizer may be better for detecting differences between treatments than the Omni mixer. At the slower speeds myofibrils consist of more sarcomeres and intermyofibril linkages could still be observed. This contrast was also seen between samples aged for 1 or 5 days with much greater degradation visually observed in the latter samples. This was supported by the quantitative data. PMID- 22061822 TI - Addition of alpha-ketoglutarate enhances formation of volatiles by Staphylococcus carnosus during sausage fermentation. AB - The effect of leucine and alpha-ketoglutarate addition on transamination of branched-chain amino acids was studied in model minces inoculated with Pediococcus pentosaceus and Staphylococcus carnosus. Leucine addition changed the ratio of volatile breakdown products of leucine, isoleucine and valine but not the total amount of the volatiles and it was concluded that the amount of free amino acids does not limit transamination of amino acids. The addition of alpha ketoglutarate resulted in increased levels of methyl-branched aldehydes and insignificant positive changes in methyl-branched acid production. The results were verified in real fermented sausages with no, low (0.09% w/w) and high (0.36% w/w) addition of added alpha-ketoglutarate since the levels of the flavour intensive methyl-branched aldehydes and acids were drastically increased in sausages added alpha-ketoglutarate. The catabolism of phenylalanine was also induced by alpha-ketoglutarate and there were further indications of increased transamination of aspartate. A triangular test showed that the flavour of sausages with no and low addition of alpha-ketoglutarate could be clearly distinguished from one another. Altogether the results presented in this paper point to glutamate dehydrogenase, the enzyme catalyzing regeneration of alpha ketoglutarate, as a key enzyme in catabolism of amino acids and thereby also in aroma formation during sausage processing. PMID- 22061823 TI - Capturing of the free cysteine residue in the ligand-binding site by affinity labeling of the ORL1 nociceptin receptor. AB - All of the delta, MU, and kappa opioid receptors have a free thiol group of the Cys residue in the ligand-binding site, although its functional role is not yet known. In order to examine whether or not a similar Cys is also present in the ORL1 nociceptin receptor, we attempted to identify it by affinity labeling using a specific antagonist peptide. We first treated ORL1-expressing COS-7 cell membrane preparations with the thiol-alkylation reagent N-ethylmaleimide (NEM) to perform a binding assay using [(3)H]nociceptin as a tracer and nociceptin, an ORL1 agonist, or Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2), a nociceptin/ORL1 antagonist, as a competitor. It was suggested that ORL1 has a free Cys in its ligand-binding site, since the NEM treatment reduced the population of ligand-binding sites. This was further confirmed by affinity labeling using Cys(Npys)-Arg-Tyr-Tyr-Arg Ile-Lys-NH(2) with the SNpys group that can react with a free thiol group, resulting in the formation of a disulfide bond. This affinity labeling was approximately 23 times more specific than NEM alkylation. The results revealed that the ORL1 nociceptin receptor does contain a free Cys residue in the ligand binding site. PMID- 22061824 TI - A specific protein disorder catalyzer of HIV-1 Nef. AB - The HIV-1 auxiliary protein Nef is required for the onset and progression of AIDS in HIV-1-infected persons. Here, we have deciphered the mode of action of a second-generation inhibitor of Nef, DLC27-14, presenting a competitive IC(50) of ~16 MUM measured by MALDI-TOF experiments. Thermal protein denaturation experiments revealed a negative effect on stability of Nef in the presence of a saturating concentration of the inhibitor. The destabilizing action of DLC27-14 was confirmed by a HIV protease-based experiment, in which the protease sensitivity of DLC27-14-bound Nef was three times as high as that of apo Nef. The only compatible docking modes of action for DLC27-14 suggest that DLC27-14 promotes an opening of two alpha-helices that would destabilize the Nef core domain. DLC27-14 thus acts as a specific protein disorder catalyzer that destabilizes the folded conformation of the protein. Our results open novel avenues toward the development of next-generation Nef inhibitors. PMID- 22061825 TI - Bis(oxyphenylene)benzimidazoles: a novel class of anti-Plasmodium falciparum agents. AB - A small library of 26 2,2'-[alkane-alpha,omega-diylbis(oxyphenylene)]bis-1H benzimidazoles has been prepared and evaluated against Giardia intestinalis, Entamoeba histolytica, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum. Among the tested compounds, eight derivatives (17, 19, 20, 24, 27, 30, 32 and 35) exhibited an anti-Plasmodium falciparum activity characterized by IC(50) values in the range of 180-410 nM (0.11-0.21 MUg/mL) and selectivity indexes (IC(50) rat skeletal myoblasts L6 cells vs IC(50)P. falciparum K1 strain) varying between 92 and more than 450. Two of the eight novel drug leads, namely compounds 19 and 32, were also active against G. intestinalis and L. donovani with selectivity indexes of 122 and >164 respectively. PMID- 22061826 TI - Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase. AB - We report on Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) inhibitory activities of a series of new 3'- and 5'-modified thymidine analogues including alpha- and beta-derivatives. In addition, several analogues were synthesized in which the 4-oxygen was replaced by a more lipophilic sulfur atom to probe the influence of this modification on TMPKmt inhibitory activity. Several compounds showed an inhibitory potency in the low micromolar range, with the 5'-arylthiourea 4-thio-alpha-thymidine analogue being the most active one (K(i)=0.17 MUM). This compound was capable of inhibiting mycobacteria growth at a concentration of 25 MUg/mL. PMID- 22061828 TI - Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats. AB - Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. In the context of the European InnoMed PredTox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicin-induced nephrotoxicity. Male Wistar rats were treated with 25 and 75 mg/kg/day subcutaneously for 1, 3 and 14 days. Histopathology observations showed mild tubular degeneration/necrosis and regeneration and moderate mononuclear cell infiltrate after long-term treatment. Transcriptomic data indicated a strong treatment-related gene expression modulation in kidney and blood cells at the high dose after 14 days of treatment, with the regulation of 463 and 3241 genes, respectively. Of note, the induction of NF-kappa B pathway via the p38 MAPK cascade in the kidney, together with the activation of T-cell receptor signaling in blood cells were suggestive of inflammatory processes in relation with the recruitment of mononuclear cells in the kidney. Proteomic results showed a regulation of 163 proteins in kidney at the high dose after 14 days of treatment. These protein modulations were suggestive of a mitochondrial dysfunction with impairment of cellular energy production, induction of oxidative stress, an effect on protein biosynthesis and on cellular assembly and organization. Proteomic results also provided clues for potential nephrotoxicity biomarkers such as AGAT and PRBP4 which were strongly modulated in the kidney. Transcriptomic and proteomic data turned out to be complementary and their integration gave a more comprehensive insight into the putative mode of nephrotoxicity of gentamicin which was in accordance with histopathological findings. PMID- 22061827 TI - Ovarian expressed microsomal epoxide hydrolase: role in detoxification of 4 vinylcyclohexene diepoxide and regulation by phosphatidylinositol-3 kinase signaling. AB - 4-vinylcyclohexene diepoxide (VCD) is a metabolite of 4-vinylcyclohexene (VCH) which has the potential to be formed in the ovary through CYP2E1 activity. VCD specifically destroys primordial and small primary follicles in the rodent ovary. Mouse ovaries exposed to VCD demonstrate increased mRNA and protein expression of microsomal epoxide hydrolase (mEH), and an inactive tetrol metabolite (4-(1,2 dihydroxy)ethyl-1,2-dihydroxycyclohexane) can be formed in mouse ovarian follicles, potentially through detoxification action of mEH. In contrast, mEH can bioactivate another ovotoxic chemical, 7,12-dimethylbenz[a]anthracene (DMBA) to a more toxic compound, DMBA-3,4-diol-1,2-epoxide. Thus, the present study evaluated a functional role for mEH during detoxification of VCD. Additionally, because inhibition of the phosphatidyinositol-3 kinase (PI3K) signaling pathway in a previous study protected primordial follicles from VCD-induced destruction, but accelerated DMBA-induced ovotoxicity, a role for PI3K in ovarian mEH regulation was evaluated. Using a post-natal day (PND) 4 Fischer 344 rat whole ovary culture system inhibition of mEH using cyclohexene oxide during VCD exposure resulted in a greater (P<0.05) loss of primordial and small primary follicles relative to VCD treated ovaries. Also, relative to controls, meh mRNA was increased (P<0.05) on day 4 of VCD (30 MUM) exposure, followed by increased (P<0.05) mEH protein after 6 days. Furthermore, inhibition of PI3K signaling increased mEH mRNA and protein expression. Thus, these results support a functional role for mEH in the rat ovary, and demonstrate the involvement of PI3K signaling in regulation of ovarian xenobiotic metabolism by mEH. PMID- 22061829 TI - The usefulness of muscle color and pH for segregating beef carcasses into tenderness groups. AB - A total of 3435 beef carcasses from animals 11 to 14 months of age (472 bulls, 978 heifers, 1985 steers) were evaluated over a ten year period to determine the usefulness of measurements of muscle color and pH for segregating carcasses into tenderness groups. All carcasses were aged for 6 days at 2 degrees C. Color and pH measurements were obtained on the longissimus? muscle. A loin steak from the eleventh-twelfth thoracic vertebrae interface was microwaved to approximately 70 degrees C to determine shear force values. Steers had the lowest ultimate pH and shear force values and bulls had the highest (P=0.0001). Steers also had lighter colored lean (P=0.0001) than bulls and heifers (i.e. higher mean colorimeter readings). Arbitrary segregation of carcasses into tenderness groups based on shear force values (?6.0 tender; >6.0 tough) resulted in the tender group having higher colorimeter readings (17.40 versus 16.76, P=0.0001) and ultimate pH values (5.70 versus 5.69, P=0.02) and lower shear force values (4.89 versus 7.65, P<0.0001). Year and breed effects were observed in all three traits (P=0.0001). However, time trends were not detected and the range in shear force values among breeds was relatively narrow (6.02-6.74). Subjective color scores, colorimeter readings, and ultimate pH values accounted for 48% or less of the variation in shear force values in all sex, year, and breed groups indicating that generally none of these traits were highly related to tenderness in a linear fashion. Arbitrary segregation of carcasses into tenderness groups based upon shear force value resulted in consistently higher shear force values for the toughh group (SV>6.0) and lower values for the tender group (SV?6.0) (P<0.05) than the overall mean shear force value in all sex groups. Plotting of colorimeter readings and ultimate pH values against shear force values resulted in peaks within the range of colorimeter readings 8.5-16.5 and pH values 5.8-6.19. Segregation of carcasses with colorimeter readings within the range 8.5-16.5 was effective in segregating the tough ess steer and heifer carcasses and the tender bull carcasses, while segregation based upon pH values between 5.8 and 6.19 was effective in segregating the tough carcasses in all sex groups. Segregation based on both color and pH appeared to offer little advantage over the use of pH alone. Segregation of beef carcasses with ultimate longissimus pH values between 5.8 and 6.19 appears to be an easy, nondestructive, practical means to effectively remove the majority of tough carcasses (shear value >6.0) in all three sex groups, regardless of breed. PMID- 22061830 TI - Changes in phospholipids of buffalo meat during processing and storage. AB - Effect of broiling and pressure cooking as well as alterations during refrigerated (4 degrees C) and frozen (-10 degrees C) storage on the phospholipids of adult male buffalo muscles viz. Triceps brachii (TB), Longissimus dorsi (LD) and Biceps femoris (BF), i.e. from three different locations were studied. Muscles differed significatly in their total lipid and phospholipid content. Cooking methods significantly altered the total phospholipid content and its fractions. Storage period did not show any significant effect on total phospholipids during refrigerated and frozen storage, whereas certain phospholipid classes viz. lysophosphatidyl choline and lysophosphatidyl ethanolamine + sphingomyelin increased significantly and major phospholipid classes viz. phosphatidyl choline and phosphatidyl ethanolamine decreased significantly. The changes in phospholipid classes were similar both in refrigerated and frozen samples but relatively more pronounced in the former. Palmitic, stearic, oleic and linoleic acids were the four predominant fatty acids in the phospholipids of buffalo meat. The effects associated with the location of muscles were evident. Differences in fatty acid composition of individual muscles in response to heat processing were observed. Heat processing significantly increased the total saturates in TB and LD muscles while it decreased in BF. The total monounsaturated and total polyunsaturated fatty acids of phospholipids decreased during refrigerated and frozen storage indicated by a significant decreass in oleic, linoleic and arachidonic acids. PMID- 22061831 TI - The effects of electrical stimulation, thawing, ageing and packaging on the colour and display life of lamb chops. AB - Electrical stimulation, freezing and thawing, ageing and type of packaging used during ageing are factors which could influence the final colour of meat. The experiment reported here determined the individual and additive effects of these factors in displayed lamb. Initial panel scores for colour of chops were increased by electrical stimulation and decreased by thawing and by ageing for up to six weeks. Chops from loins which had been aged in vacuum pack had higher initial scores than those aged in oxygen-permeable film. Hunter colour values for chops from stimulated carcasses were much less variable than those for chops from unstimulated carcasses. Stimulation, therefore, produced a more uniform product. Hunter L, a and b values all declined during display, the greatest decline being in a (redness). Hunter values were not good predictors of initial panel scores but Hunter a and hue (a b ) both declined with panel scores. With no ageing, the display life of stimulated chilled lamb was longer than that of unstimulated lamb, but this advantage disappeared after ageing for 2 weeks in a vacuum pack. The display life of thawed unstimulated lamb was only slightly inferior to that of chilled unstimulated lamb when both were vacuum-packed, but thawed stimulated lamb resulted in a much reduced display life. Ageing of loins in oxygen-permeable film adversely affected display life of chops. Total drip loss from rigor to the end of display was significantly affected by all treatments except stimulation. The dominant cause of drip loss was the freeze-thaw treatment. In chilled and thawed lamb, ageing increased drip. Packaging had a lesser effect on drip. PMID- 22061832 TI - Use of the Tecpro Pork Quality Meter for assessing meat quality on the slaughterline. AB - Conductivity measurements made with the Tecpro Pork Quality Meter at either 45 min or about 20 h post mortem on 224 pig cacassees which exhibited a wide range of raw meat quality were moderately correlated with initial pH (pH(45); r = 0.54 and 0.62) but less well correlated with reflectance (r = 0.32 and 0.37), drip loss (r = 0.34 and 0.47 and other objective measures of meat quality in the M. Longissimus dorsi. Measurements did not allow differentiation between normal and dark, firm, dry (DFD) meat but were of some value in identifying carcasses producing potentially pole, soft, exudative (PSE) meat. In the UK they would be more useful for monitoring meat quality in large groups or populations of pigs, than for categorising individual carcasses for grading on technological purposes. PMID- 22061833 TI - Modelling of the formation of pale, soft and exudative meat: Effects of chilling regime and rate and extent of glycolysis. AB - The high drip losses and softness of pale, soft and exudative meat are caused by denaturation of myosin before rigor. A simple predictive model is described based on calculations of the time-course of myosin denaturation in carcasses using the known dependence of the rate of denaturation of isolated myosin on temperature and pH (Penny, 1967a). The fraction of myosin denatured increases with the rate of pH fall, then reaches a maximum at a rate of pH fall that depends on the chilling conditions, and finally decreases. The relationship between drip loss and pH(45) value (Warris & Brown, 1987) is well explained by the calculations. The fraction denatured also increases as the final pH decreases, particularly at higher rates of pH fall. Increasing the chilling rate causes a marked reduction in the fraction denatured at low rates of pH fall but is only slightly effective if the rate of glycolysis is very high. PMID- 22061834 TI - Effect of citric acid and citrate on the shelf stability of canned liver paste processed at reduced F(0) values. AB - Citric acid and the combination of citric acid and citrate, in a few cases enriched with potassium sorbate, were tested for their stabilizing effect in a canned liver paste processed at reduced F(0) values. pH values of the rest products ranged from 5.24 to 5.76; a(w) values varied from 0.950 to 0.972. F(0) values of 0.05, 0.30 and 0.85 were applied. Before sterilization, the paste doughs were contaminated with mixtures of bacterial spores. Heated packages were challenged by incubation at 30 and 55 degrees C for up to about 2 years. Incubated packages with the standard formulation at an F(0) of 0.05 showed the first blown cans at 30 degrees C after 24 days. Starting from this point, at this F(0) value products with a variable, but increased, bacteriological stability were observed. At an F(0) of 0.30 a perfectly stable product at 30 degrees C was observed after addition of 0.14% w/w citric acid only (product pH 5.69). Moreover, all tested combinations of additives at F(0) values of 0.30 and 0.85 yielded stable products at this incubation temperature. At the higher F(0) value a clear effect with respect to delaying thermophilic spoilage was observed. The effect of the application of potassium sorbate-in combination with both other additives-at F(0) values of 0.30 and 0.85 proved to be negligible. PMID- 22061835 TI - Sex differences in the effects of perinatal anoxia on dopamine function in rats. AB - Birth complications involving reduced oxygen to the fetus pose risks for neurodevelopmental disorders like schizophrenia and ADHD, which involve central dopamine (DA) dysfunction and also show gender differences in incidence or severity. Here, we examine possible sex differences in the long-term consequences of perinatal anoxia in the rat, on central DA systems and DA-mediated behaviour. As adults, sensorimotor gating (prepulse inhibition, PPI) was differentially affected by anoxia in males and females, tending to be impaired only in males. Apomorphine-induced suppression of PPI was especially pronounced in males. Anoxia caused increases in amygdala DA levels in both sexes. However, sex-specific changes in DA and metabolite levels in prefrontal cortex and nucleus accumbens were found, suggesting a possible basis for some of the observed gender biases in certain neurodevelopmental disorders, sensitive to birth hypoxia. PMID- 22061836 TI - Prostaglandin E2 receptor expression in the rat trigeminal-vascular system and other brain structures involved in pain. AB - Prostaglandin E(2) (PGE(2)) is considered to be a key mediator in migraine pathophysiology. PGE(2) acts via four receptors (EP(1)-EP(4)) but their distribution in the brain districts implicated in migraine has yet to be delineated. We quantified amount of mRNA and protein expression for the EP receptors in both peripheral and central structures involved in pain transmission and perception in migraine: dura mater, cerebral arteries, trigeminal ganglion, trigeminal nucleus caudalis, periaqueductal grey, thalamus, hypothalamus, cortex, pituitary gland, hippocampus and cerebellum. In the trigeminal-vascular system (TVS) we found highest expression of EP(1) and EP(2) protein in the trigeminal nucleus caudalis. EP(3) and EP(4) mRNA expression were highest in the trigeminal ganglion. Within intracranial structures EP(1) mRNA and protein expression were significantly higher in pituitary gland and cerebellum than in dorsal root ganglia (peripheral control), whereas the EP(2) mRNA and protein were highly abundant in the pituitary gland. EP(3) mRNA was mainly found in thalamus and hypothalamus. The most robust mRNA and protein expression for EP(4) receptor was seen in the dorsal root ganglion. In conclusion, all four receptors are located in areas implicated in migraine supporting the possible involvement of PGE(2) in this disease. PMID- 22061837 TI - Whole body vibration training reduces plantar foot sensitivity but improves balance control of healthy subjects. AB - The goal of this study was to investigate the effects of short-time whole body vibration (WBV) training on foot vibration sensitivity of healthy subjects. Furthermore, the effects of WBV on a balance task (one-leg stand) were also evaluated. 30 young healthy subjects participated in the study. Vibration perception thresholds and balance were measured prior and after a single session of a 4-min WBV training (27Hz, 2mm horizontal amplitude). Thresholds were measured at 200Hz at three anatomical locations of the plantar foot area (first and fifth metatarsal heads and heel). Body balance was quantified using the length as well as the area described by the center of pressure (COP) at quiet, one-leg standing. Whereas vibration thresholds significantly increased after WBV training at all measured locations, there was a significant decrease in the balance related parameters after WBV exercise. The results indicate that the above-threshold, sinusoidal vibration used during WBV training is not an adequate strategy to stimulate/improve vibration sensitivity. The improvements seen in balance after WBV are likely to have neuromuscular mechanisms as their main component rather than increased foot sensitivity. PMID- 22061838 TI - Blocking of acquisition of a taste aversion by a context experienced prior to the taste. AB - This experiment tested the proposal that events taking place before a rat has access to a taste can proactively interfere with acquisition of an aversion to the taste when this has been followed by lithium chloride injection. Rats were initially given context discrimination whereby placement in one distinctive context (target) was followed by lithium injection, while placement in a second context (safe) was followed by saline injection. In the subsequent 1-trial taste conditioning session, rats were first placed in either their target context (Blocking group), their safe context (Control-Safe group) or a neutral context (Control-Neutral group), then given access to sucrose and 30 min later were injected with lithium. Subsequent tests of sucrose intakes revealed a blocking effect. These results indicate that proactive interference with taste aversion learning by a context can occur that is unlikely to be based on generalization decrement. PMID- 22061839 TI - An overview: in vitro models of HCV replication in different cell cultures. AB - Although much of productive research has been conducted in the field of molecular virology of Hepatitis C virus (HCV) regarding its genes, gene functions and proteins, development of an efficient cell culture model for its replication remained a focused area. Focus has been directed to establish HCV in vitro replication system. This replication system should mimic its intrahepatic pathogenesis so that antivirals should be screened and in vitro gene profiling of HCV induced pathogenesis should be worked out. Since 1990 various experimental approaches and strategies have been utilized in phase of development of a robust replication model for HCV, and success has been reported for a few genotypes. Still the work is going on to have more success in availing such robust replication models for all the genotypes. This will help to have a common antiviral strategy against HCV induced pathogenesis involving any genotype or subtype. PMID- 22061840 TI - The effect of simulated transport of fresh meats on their water-holding capacity as assessed by various methods. AB - This study was designed to establish the effects of transport vibrations on the water-holding capacity of fresh non-stimulated veal and pork and electrically- and non-stimulated beef. Furthermore, drip production was followed during storage by various methods which were compared for their suitability in industrial practice and scientific research. During storage, the amount of drip increased, whilst the rate of drip formation decreased. Filter paper wetness measured at 1 day post mortem was positively correlated with drip lost over a period of 2 weeks of refrigerated storage in poly-ethylene bags (method 1) and poly-propylene containers (method 2). This suggests that the filter paper wetness test may be useful to predict drip loss of stored meat. Simulated transport did not result in higher drip losses, although a significant increase in filter paper wetness from the fresh cut surface of veal and pork was found, suggesting that transport affects the initial rate of drip production, but not the total amount of drip. In beef, transport simulation resulted in an increase in filter paper wetness from the surface of electrically-stimulated meat, stored for 1 or 2 weeks, indicating that fluid loss was elevated due to transport vibrations. However, this effect seemed to be related to the intrinsic water-holding capacity of the sample: meat with a low intrinsic water-holding capacity seemed to be more sensitive to transport vibrations than meat with a high intrinsic water-holding capacity. PMID- 22061841 TI - Influence of dietary fat and vitamin E supplementation on alpha-tocopherol levels and fatty acid profiles in chicken muscle membranal fractions and on susceptibility to lipid peroxidation. AB - Broiler chickens were fed a basal feed supplemented with 10% tallow or olive oil and varying levels of vitamin E (20 and 200 mg vitamin E/kg feed). The concentration of alpha-tocopherol in the membranes of breast and thigh muscles was significantly influenced by the alpha-tocopherol level in the feed (p < 0.001). Deposition of vitamin E was not influenced by the type of oil in the feed, except in the mitochondrial fraction of breast where the vitamin E concentration was higher in those fed olive oil than in those fed tallow (p < 0.05). Dietary oil influenced the fatty acid composition of the muscle membranal fractions (p < 0.001). The oxidative stability of the membranal fractions tended to increase with increasing concentrations of alpha-tocopherol in the membranal fractions. In conclusion, the supplementation of vitamin E appeared to enhance the stability of muscle to oxidation. Thus, incorporation of alpha-tocopherol into the membranes via dietary manipulation helped in stabilizing the membrane bound lipids. PMID- 22061842 TI - Direct transesterification of total fatty acids of adipose tissue, and of freeze dried muscle and liver with boron-trifluoride in methanol. AB - The purpose of this study was to demonstrate direct transesterification of fatty acids of tissue total lipids with boron-trifluoride in methanol. Adipose tissue, muscle, and liver samples obtained from market-weight lambs, were transesterified with 14% boron-trifluoride in methanol at 80 degrees C. Total lipids of additional samples were first solvent-extracted and then transesterified with 14% boron-trifluoride in methanol. Thin layer Chromatographic evaluation revealed quantitative conversion of triacylglycerol- and polar lipid-fatty acids to fatty acid methyl esters using direct transesterification. No differences in fatty acid composition were observed for adipose tissue (p > 0.05); however, for muscle, 20:4 was greater (p = 0.01) with direct transesterification. For liver, greater concentrations of fatty acids were observed for the direct transesterification method (p < 0.02). Weight percentages of adipose and muscle fatty acids were unchanged from 15 to 180min of direct transesterification; however, 120 and 90 min of direct transesterification were required for adipose tissue and muscle, respectively, for complete transesterification. It was concluded that for analysis of total fatty acids, one-step direct transesterification with boron trifluoride in methanol is a useful and acceptable procedure. PMID- 22061843 TI - Proteolysis and tenderisation in reindeer (Rangifer tarandus tarandus L.) bull longissimus thoracis muscle of varying ultimate pH. AB - Proteolysis and tenderisation in reindeer (Rangifer tarandus tarandus L.) M. Longissimus Thoracis were studied. Mm. Longissimus ( the part cut out between vertebrae thoracales 6-7 and vertebrae lumbales 5-6) from 12 reindeer bulls (age 1 1 2 years) were, after ultimate pH and temperature measurements, excised and then sampled at various times post mortem for determination of sarcomere length, Warner-Bratzler shear force, calpain and calpastatin activities, cathepsins B + L activities, active site titration of cystatin-like inhibitors, myofibrillar protein degradation, collagen content and heat solubility. Upon measurement of ultimate pH, the carcasses were divided into two pH groups; normal pH (5.65 <= pH <= 5.79) and high pH (pH >= 5.80). Temperature and pH fall were relatively rapid in all reindeer carcasses. Sarcomere lengths tended to be shorter in the carcasses of the high pH group. In the three carcasses with the highest ultimate pH values (6.11, 6.34 and 6.38), sarcomere lengths were around or below 40% of resting length (1.37MUm, 1.25MUm and 1.25MUm, respectively) which is likely associated with the occurrence of heat shortening. Total collagen content was higher and heat solubility lower in the high pH group, which could have masked differences in tenderness. However, all reindeer longissimus muscle samples were found to be extremely tender regardless of ultimate pH. By 3 days post mortem Warner-Bratzler shear force values were varying between 2.1-4.9 kg cm(2). There was a significantly higher activity of MU-calpain in the high pH group at 1 day post mortem. No differences in shear force, myofibrillar protein degradation as observed by SDS-PAGE, m-calpain and calpastatin activities, calhepsins B+ L activities or the levels of cystatin-like inhibitors were found between the two pH groups. PMID- 22061844 TI - The problem of taint in pork: 1. Detection thresholds and odour profiles of androstenone and skatole in a model system. AB - Detection thresholds of androstenone and skatole were established using a trained 10-member sensory panel. Odour profiles for these compounds were also developed using a model system comprising a lipid base spiked with synthetic androstenone and skatole. A total of 2160 presentations were used for the determination of sensory thresholds which were obtained using the Ascending Method of Limits with a 3-AFC (Alternate Forced Choice) mode of presentation. Preliminary odour profiles were obtained by three consensus-profiling sessions. Character notes developed were then validated by profiling four classes of model samples containing androstenone, skatole, a mixture of skatole plus androstenone and a mixture of skatole plus androstenone plus indole. Individual sensory thresholds for the ten panel members varied between 0.2 to 1.0 MUg g(-1) for androstenone and 0.008 to 0.06 MUg g(-1) for skatole, leading to group thresholds of 0.426 MUg g(-1) and 0.026 MUg g(-1) for androstenone and skatole, respectively. The important descriptors for the odour of androstenone included; sweaty, ammonia, dirty, parsnip, silage, nosefeel and acrid. Among these, only the sweaty note was found to be a significant (p < 0.05) basis for separating pure samples of androstenone from pure samples of skatole by the panel. The important descriptors for the odour of skatole were; mothball, musty and body reaction. Both the mothball and musty notes were a significant (p < 0.001 to p < 0.05) basis for distinguishing between either pure samples of skatole or mixtures containing skatole from pure samples of androstenone. The results show that androstenone and skatole are synergistic, but only in relation to the descriptors defining intensity of the odours, and not in those defining the character of their individual odours. PMID- 22061845 TI - Acceptability and functional properties of restructured roast from frozen pre rigor injected beef. AB - Restructured beef roasts, made to a standardized formulation, were prepared using the following types of meat that had been stored at - 18 degrees C for 5 or 10 weeks: grass-fed bull beef pre-rigor injected with a salt/phosphate brine; uninjected grass-fed bull beef; uninjected grain-fed beef; a 50:50 blend of pre rigor injected grass-fed bull beef and grain-fed beef; and a 50:50 blend of uninjected grass-fed bull beef and grain-fed beef. After frozen storage, pre rigor injected beef had a higher (p < 0.05) ultimate pH than uninjected beef . Grain-fed beef had the lowest ultimate pH. Roasts made from pre-rigor injected beef were redder (higher Hunter a(*) values) than roasts made with uninjected beef (p < 0.05). Roasts made from grain-fed beef were lighter and looked more cooked (higher L(*) and lower a(*) values respectively) than those made with grass-fed beef. Extending frozen storage to 10 weeks decreased the cook yield (p < 0.05), peak force (p < 0.001) and extensibility (p < 0.05). Consumer panellists preferred (p < 0.05) roasts made from pre-rigor injected beef for tenderness, juiciness and overall acceptability compared with roasts made from uninjected beef. PMID- 22061846 TI - The hygienic and organoleptic qualities of ground beef prepared from manufacturing beef pasteurized by immersion in hot water. AB - Groups of 24 lots of manufacturing beef were untreated or treated by immersion in water of 85 degrees C for 15 s or 1 min. Each lot was ground, and total counts, coliforms and Escherichia coli were enumerated in samples from each ground lot. Each ground lot was divided into two portions, and their appearances were assessed by a panel 2, 24 and 48 hr after the treatment of the beef. Treatment for 15 s reduced the numbers of non-thermotolerant bacteria, including coliforms and E. coli, by about one order of magnitude. Treatment for 1 min reduced the numbers of non-thermotolerant bacteria by about two orders of magnitude, with reduction of the numbers of coliforms and E. coli in all samples to below the detection level of 1 CFUg(-1). Ground beef prepared from treated product tended to appear lighter in colour and duller than ground beef from untreated product, and to be more discoloured after 24 hr. However, the changes in the appearances of ground beef resulting from the treatment of manufacturing beef were small, and seemingly would not render the ground meat unacceptable for retail display. In a triangle taste test, there was no significant difference (p > 0.05) in the flavour of hamburger patties prepared from untreated beef or from beef treated for 1 min at 85 degrees C. The findings suggest that pasteurization of manufacturing beef could be a commercially useful technique for reducing the risk of infection with enteric bacteria to consumers of mass produced hamburger patties. PMID- 22061847 TI - The effects of hot water pasteurizing treatments on the appearances of pork and beef. AB - Portions of post- and pre-rigor pork and beef were treated by immersion in water of 75 or 85 degrees C for 5, 10, 15 or 20 s. The appearances of untreated and treated cut muscle, fat, membrane covered and cut bone surfaces, and the overall appearances of treated and untreated meat pieces, were assessed by a 5-member panel 2 hr and 24 hr after each treatment. At those times, CIE L(*)a(*)b(*) values were obtained for cut-muscle surfaces. The appearances of surfaces covered by membrane, of fat and cut bone surfaces of pre-rigor pork and beef, and of fat and cut bone surfaces of post-rigor pork, were not persistently degraded by any treatment. However, the appearances of fat and cut bone surfaces of post-rigor beef were persistently degraded by the harsher treatments, apparently because of pre-treatment staining of fat and changes in the bone marrow. Panel scores for the overall appearance and for the appearance of cut muscle surfaces were generally the same for each meat piece. All treatments caused patchy bleaching of cut muscle. The degraded appearances of pre- and post-rigor pork and post-rigor beef muscle persisted at 24 hr, but the appearances of beef muscle treated pre rigor improved between 2 and 24 hr. Most treated muscle gave increased CIE L(*) values and decreased a(*) and b(*) values as compared with untreated portions from the same primal cut. However, CIE b(*) values for pre-rigor beef muscle were higher than for untreated muscle 2hr after treatment, but lower than for untreated muscle 24 hr after treatment. It appears that pasteurizing treatments cannot be applied to meat without some degradation of the appearances of cut muscle surfaces, which will persist in pork treated pre- or post-rigor and in beef treated post-rigor, but which will partially resolve during the storage of beef treated pre-rigor. PMID- 22061848 TI - Effects of high intensity ultrasound treatment, storage time and cooking method on shear, sensory, instrumental color and cooking properties of packaged and unpackaged beef pectoralis muscle. AB - Beef pectoralis muscles were removed at 24 h post mortem from nine steers, and samples were vacuum packaged and exposed to high-intensity ultrasound (20 kHz, 22 W/cm(2)) for 0, 5 or 10 min, then aged for 1, 6 or 10 days before evaluation of purge and cooking losses, instrumental shear and color and sensory traits (Experiment 1). For Experiment 2, unpackaged beef pectoralis muscle samples from eight steers were subjected to ultrasonic cooking, boiling, convection cooking or ultrasound treatment for 5 or 10 min followed by cooking in a convection oven. Neither duration of sonication nor storage of packaged pectoralis muscles affected (p > 0.05) storage purge or cooking losses, shear properties or sensory characteristics (Experiment 1). However, muscles receiving ultrasonic treatment showed tendencies for reduced peak force and total work to shear. Increased length of storage caused pectoralis muscles to become more vivid red-orange colored (p < 0.05), whereas ultrasonic treatment caused muscles to become less vivid, less red and more orange colored (p < 0.05). Ultrasonically cooked pectoralis muscles (Experiment 2) had lower (p < 0.05) cooking losses than muscles cooked by other methods. Both ultrasonic cooking and boiling were faster than convection cooking only and ultrasound exposure followed by convection cooking. Additional studies are needed to verify the ability of ultrasound to promote improved cooking, sensory and shear properties of muscle. PMID- 22061849 TI - Dried sausages fermented with staphylococcus xylosus at different temperatures and with different ingredient levels. Part IV. Amino acid profile. AB - Sausages with added Staphylococcus xylosus were fermented at different temperatures and with different added levels of salt, glucose, nitrite, nitrate and Pediococcus pentosaceus in accordance with a six-factor fractional design. The amounts of individual amino acids were measured and the effects of temperature and different ingredients on the amino acid profile were tested using multiple linear regression and analysis of variance. Also, the amino acid profile was correlated to the level of volatile compounds by partial least squares analysis. The study showed that the level of free amino acids was significantly affected by the different factors. High fermentation temperature and nitrite content increased the amount, while high contents of salt, nitrate, glucose and P. pentosaceus lowered the amount of free amino acids. In general, temperature and nitrate had the greatest influence. It was shown that the amounts of the volatile compounds, 2-methyl propanal, 2- and 3-methyl butanal, were inversely correlated with the amounts of valine, isoleucine and leucine, respectively, indicating that those volatiles were degradation products of the latter. PMID- 22061850 TI - Proteolysis in dry fermented sausages: The effect of selected exogenous proteases. AB - The effect of three commercial proteases (pronase E from Streptomyces griseus, aspartyl proteinase from Aspergillus oryzae and papain) on protein breakdown and the sensory characteristics of dry fermented sausages was investigated. Water soluble, non-protein, 5% phosphotungstic acid soluble, 5% sulphosalicylic acid soluble and total volatile basic nitrogen contents increased during fermentation, stabilizing later until the end of ripening (26th day). Nitrogen values were always greater in the aspartyl proteinase added batch in comparison with the other protease added batches. Total free amino acid changes showed a similar pattern to those observed for the 5% sulphosalicylic acid soluble nitrogen. The electrophoretic studies demonstrated that proteolysis of high molecular weight myofibrillar and sarcoplasmic proteins was more prominent in protease added batches. It was especially intensive in papain one. The dominant amino acids at the end of ripening were similar in all batches. Tyramine and histamine increased throughout ripening. No significant differences in sensory properties were found between control and pronase E and papain added batches, but they were significantly different (p < 0.01) from the sausages containing aspartyl proteinase, due to an excessive softening. The effect of exogenous enzyme addition on the flavour potentiation of dry fermented sausage is discussed. PMID- 22061851 TI - Contribution to improving the meat water holding capacity test by the filter paper press method. A comparison of three methods for measuring areas. AB - Tests of meat water holding capacity (WHC) by the filter paper press method in bovine muscles were assayed. Two rapid methods to evaluate the liquid impregnation areas on the filter paper were used in opposition to the classic planimetric method. A special "reticular filter paper" for direct measurement of spot areas was designed. Data from 1113 meat WHC tests of Longissimus dorsi, Semitendinosus, Semimembranosus, Biceps femoris and Adductor muscles were assayed. It was verified that the reticular method has a good precision with coefficient of variation, CV%, between 4.04 and 2.64% for meat 'M' and total 'T' areas, respectively. The accuracy of the reticular method was also very high, with R(2) = 99.54% for 'T' and 97.06% for 'M'. The caliper rule method showed an acceptable accuracy, with values R(2) = 98.05 and 90.76% for 'T' and 'M', respectively. Their precision, however was somewhat smaller than reticular measures, with CV% between 5.51 and 7.37% for 'T' and 'M', respectively. PMID- 22061852 TI - Composition, solubility and gel properties of salt soluble proteins from two bovine muscle types. AB - The composition, pH solubility profile and thermal gelation behavior of two bovine muscles, vastus intermedius (VI, predominately red fibers) and semimembranosus (SM, predominantly white fibers) were compared. VI had a higher fat content and pH and lower protein content than SM. Between pH 5.2 and 5.8, the salt soluble proteins (SSP) from SM were more soluble than those from VI at the same pH, whereas solubilities above pH 6.0 were similar. Properties of SSP gels were measured at pH 5.5 and 6.1, the ultimate pH for SM and VI, respectively. Water lost from the VI gels due to syneresis was about 3 times greater than that lost from SM gels. VI gels prepared at pH 5.5 were firmer (p<0.05) than at pH 6.1, whereas deformability of SM gels at pH 6.1 were greater (p<0.05) than at pH 5.5. No differences (p>0.05) were observed between the firmness or deformability of VI or SM gels when compared at the same pH. Results suggest that ultimate muscle pH and fiber type do influence the properties of bovine SSP gels, although the effect is not as great as that previously reported for poultry muscle proteins. PMID- 22061853 TI - Bone marrow measurements for mechanically recovered products from machines that press bones. AB - Meat from Advanced Meat Recovery (AMR) systems is being used in increasing amounts in meat products, but authenticity issues resulting from the incidental inclusion of bone marrow when meat is pressed from the bones have arisen. Unfortunately, no widely accepted method for determining amount of marrow in meat from AMR systems is available. Past attempts to detect and quantify the amount of marrow in mechanically recovered products is the focus of this review. Methods for quantifying red marrow include those based on the heme pigments and on iron contained in these pigments. An immunological procedure in which antibodies are raised to bone marrow proteins and the pH method can also be used as qualitative and quantitative tests, respectively, for red marrow presence. Fatty marrow, associated with the term marrow by the public, is found in the medullary cavity of the shaft of long bones. These bones are not recommended for use in meat recovery systems, so methods for detection of fatty marrow are not addressed. PMID- 22061854 TI - Free amino acids and dipeptides in porcine muscles: differences between 'red' and 'white' muscles. AB - Three porcine muscles (m. longissimus dorsi, masseter and trapezius), chosen to represent the three main metabolic types, from 18 carcasses had their free amino acids and dipeptides quantified by reverse-phase high performance liquid chromatography (HPLC) in aqueous extracts derivatized with phenyl isothiocyanate. Of the 25 measured compounds, four amino acids and the dipeptide carnosine were closely related to the metabolic type of the three muscles. Masseter, a red oxidative muscle, had the highest contents of aspartic acid, glutamine and taurine. Longissimus dorsi, a white glycolytic muscle was characterised by the highest contents of beta-alanine and carnosine. Trapezius, an intermediate muscle, had intermediate contents. These results show that free amino acid and dipeptide contents could partly explain differences in taste of muscles from the same species. PMID- 22061855 TI - Comparison of different dietary magnesium supplements on pork quality. AB - Forty-eight crossbred (Large White*Landrace) boars were used to compare the effect of dietary magnesium aspartate (MgAsp), magnesium sulphate (MgSO(4)) and magnesium chloride (MgCl(2)) on muscle glycogenolysis and pork quality. The pigs were fed finisher feed supplemented with either MgAsp, MgSO(4) and MgCl(2) for 5 days prior to slaughter. At the abattoir, all pigs received 15 electric shocks from an electric goad 5min prior to slaughter. Pigs fed the diet supplemented with MgSO(4) had the highest plasma Mg concentrations at slaughter in comparison with pigs fed the MgAsp and MgCl(2) supplemented diets. There were no differences in plasma adrenaline and noradrenaline concentrations at slaughter between the different diets. Pigs fed the Mg diets had higher muscle glycogen concentrations in the Longissimus thoracis (LT) muscle at 5min and at 40min (except MgCl(2)) post-slaughter compared to pigs fed the control diet. Also pigs fed the Mg diets had lower muscle lactic acid concentrations in the LT at 5min post-slaughter and lower drip loss at 24hr post-slaughter compared to pigs fed the control diet. These results indicate that cheaper magnesium sources, MgSO(4) and MgCl(2), are as efficacious as MgAsp in reducing drip loss and improving pork quality. PMID- 22061856 TI - Influence of dietary alpha-tocopheryl acetate supplementation of pigs on oxidative deterioration and weight loss in sliced dry-cured ham. AB - The effect of feeding high levels of alpha-tocopherol to pigs on the susceptibility to oxidative deterioration and weight loss in dry cured hams was investigated. The alpha-tocopherol concentration in thigh muscle from pigs fed the basal and the supplemented diet (200 mg kg(-1) alpha-tocopheryl acetate) in unprocessed thighs was 8.69 and 16.87, MUg g(-1) dry matter, not including ash, respectively (p-value=0.015), while the concentration was 6.65 and 14.28 MUg g( 1), respectively, in the final products (p-value=0.011). Hams from pigs fed the basal diet oxidized more during storage (p-value=0.015) as measured by formation in thiobarbituric acid reactive substances and had a higher rate of weight loss (p-value=0.0001). The total loss in red color after 4 days of storage was similar in all treatments. However, the rate of discoloration was more pronounced during the first 2 days of storage in hams from pigs fed the basal diet (p-value=0.016). This result indicates that high dietary level of alpha-tocopheryl acetate to pigs increases the oxidative stability in dry cured hams manufactured on the basis of such pigs. PMID- 22061857 TI - Establishment and application of a polymerase chain reaction for the identification of beef. AB - A polymerase chain reaction (PCR) based method for the identification of beef by amplification of bovine 1.709 satellite DNA was established. The method not only was able to amplify raw beef DNA, but also cooked or autoclaved meat DNA. The sequence selected for amplification consisted of a 218 bp DNA fragment lying in the 1.709 satellite DNA of bovine. A pair of synthetic oligonucleotides flanking this sequence were used as printers, and genomic DNA extracted from beef samples employed as templates. Each batch of reaction mix contained Taq DNA polymerase, a buffer component, deoxynucleotide triphosphates, genomic DNA template and a pair of bovine oligodeoxynucleotide primers in a final volume of 50 MUl. The amplification of bovine DNA was performed by using 33 cycles of denaturation at 94 degrees C (40 s), annealing at 53.5 degrees C (50 s) and extension at 72 degrees C (60 s), with a 7 min extension at 72 degrees C in the last cycles. The amplified products were subjected to rapid electrophoresis in 3% agarose gel and visualized under ultraviolet illumination after ethidium bromide staining. A Hae SH restriction endonuclease test was done to verify the specificity of the PCR amplification, and the expected DNA fragments were produced. The specificity test demonstrated that this method was positive for bovine, buffalo and yak meat DNA, but negative for equine, sheep, goat, camel, swine, deer and mouse meat DNA, etc. At least 33.6 fg of DNA from raw beef samples and 0.32 pg of DNA from cooked or autoclaved beef samples were detected, respectively, by PCR. We tested 103 beef samples by PCR and obtained 100% correct identification. The method needed only 6 h for detection of meat products of all kinds. The results showed that the PCR method was sensitive, specific, convenient and rapid, so it may be suitable for rapid identification of beef. PMID- 22061858 TI - Changes in texture, cooking losses, and myofibrillar structure of bovine M. semitendinosus during heating. AB - Vacuum-packed slices of bovine semitendinosus (ST) muscle were retorted to internal temperatures of 50, 60, 70, 80, 90, 100, and 121 degrees C. Changes in texture of the meat were evaluated by measurements of Texture Profile Analysis (TPA) parameters. Changes in microstructure were evaluated using a Scanning Electron Microscope (SEM) and measuring fibre diameter and sarcomere length. Cooking losses were also estimated. During heating the TPA parameters changed independently of each other. They reached a maxima at different endpoint temperatures of the meat and then decreased. A decrease in fibre diameter was observed in samples heated to 60 and 121 degrees C. Sarcomere length decreased continuously in the range 50-121 degrees C. Cooking losses increased with increased heating temperature. Relationships between changes in sarcomere length and cooking losses and between springiness and fibre diameter were found. PMID- 22061859 TI - A comparison of carnosine and ascorbic acid on color and lipid stability in a ground beef pattie model system. AB - Ascorbic acid (0.1%) significantly inhibited metmyoglobin formation on the surface of ground beef but not in the bulk of the product where oxygen tension was lower. Carnosine (1.0%), however, significantly inhibited metmyoglobin formation and brown color development throughout the product. The combinations of carnosine and ascorbic acid were also very effective on inhibition of metmyoglobin formation and brown color development. Carnosine increased meat pH, cook yield and salt-soluble protein, but ascorbic acid had no effect on cook yield, and decreased meat pH and salt-soluble protein. Carnosine was more effective on inhibition of lipid peroxidation than ascorbic acid. Carnosine inhibited copper(II)-catalyzed ascorbate oxidation in a dose-dependent manner in model systems. Carnosine in conjunction with ascorbic acid may be useful as a meat additive for increasing shelf-life as well as stabilizing color of meat products. PMID- 22061860 TI - Postmortem meat quality and sex affect textural properties and protein breakdown of dry-cured ham. AB - Texture measurements by instrumental texture profile analysis (TPA) and protein degradation analysis by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) were performed on 30 dry-cured hams resulting from four different post-mortem meat qualities categories (PSE, RSE, RFN and DFD). The main differences were observed in dry-cured hams from PSE and RFN meat qualities. Penetration force (80%), hardness, springiness, cohesiveness and chewiness, were significantly lower (P<0.05) in PSE than in RFN quality classes. The rate of the ripening process was affected as a higher proteolysis and absence of fragments at 150 and 85 KDa in PSE in relation to RFN classes, and with an intermediate proteolysis of RSE and DFD classes. The effect of sex was observed as a significant (P<0.05) low hardness in the hams obtained from female pigs. The duration of the ripening, for a better uniformity in dry-cured ham production, should be adapted to the initial pH and to drip loss parameters of the raw material. PMID- 22061861 TI - Slicing frozen meat with an oscillating knife. AB - The forces, and hence fracture energies, required to cut frozen meat are presented in this paper and the merits of applying vibrations to a cutting blade are considered. A knife oscillating in a slicing action was used to cut horse M. semimembranosus and loin muscle M. longissimus dorsi over a range of temperatures (-1.5 degrees C to -30 degrees C) and vibration frequencies (0-1000 Hz). The blade required less force to cut when slicing than when not slicing; the decrease in force was proportional to the velocity of the slicing motion. If the average relative slicing velocity of the blade with respect to the meat was greater than 164 mm/s then the cutting force reduced significantly. The reduction was due to a lower requirement for energy to produce the new material surface (up to 80% reduction) and also a reduction in the plastic energy required to deform the off cut by the blade (up to 30% reduction). The surface energy was reduced because the fracture mechanism was altered by the slicing action. The plastic energy was reduced because the slicing blade fractured the meat fibres with less strain (and hence less material deformation around the process zone) than a blade pressed directly into the meat. Vibration frequencies of 10-100 Hz were required to generate the required slicing motion with the equipment available. A vibrating cutting blade could have a combination of chopping and slicing motions superimposed upon it. These would reduce both the friction between the knife blade and the meat, as well as the surface and plastic energy required to cut the meat. PMID- 22061862 TI - Chemometric model for describing Greek traditional sausages. AB - Chemical, physical, microbiological and sensory analyses were performed on 31 samples of Greek traditional sausages. The following attributes were recorded: fat 15.49-56.86%, moisture 21.92-65.40%, protein 14.73-26.74%, sodium chloride 2.36-4.13%, nitrites 0.0-3.26 ppm, mean nitrates 38.19 ppm, TBA value 0.42-5.33 mg malonaldehyde/kg, pH 4.74-6.74, water activity (a(w)) 0.88-0.97, firmness 0-64 Zwick units, lightness (L(*)) 25.03-35.37, redness (a(*)) 2.55-11.42, yellowness 4.42-12.96, aerobic plate count 5.48-9.32 cfu/g, lactic acid bacteria (LAB) 5.26 9.08 cfu/g, micrococci/staphylococci 4.11-6.91 cfu/g and Gram (-) bacteria 1.78 6.15 cfu/g. Mean sensory scores ranged from 3.14 to 3.54 on a 5-point hedonic scale. Two statistical analysis programmes (Praxitele and SPSS) were used for characterising and assessing the properties of sausages. The first two principal components (PC1-2) derived by SPSS (50.5% variance) describe more satisfactorily the variance than the corresponding PC1-2, PC1-3 obtained by Praxitele (40.4% variance). High consumer preference was strongly related to satisfactory appearance and strong taste, high LAB count, medium fat content, medium firmness and lightness (L(*)(surface)). Extreme attribute values (high or low) for firmness, moisture and fat content, low salt content and low taste were related to low consumer preference. PMID- 22061863 TI - A novel splicing mutation in FKBP10 causing osteogenesis imperfecta with a possible mineralization defect. AB - Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by bone fragility and osteopenia, with a broad spectrum of clinical severity. The majority of cases are dominantly inherited and due to mutations in type I collagen genes, whereas recessive forms are less frequent and attributable to mutations in different genes involved in collagen I post translational modifications and folding (prolyl-3-hydroxylase complex, SERPINH1, FKBP10). We report the case of a patient with an initially mild and then progressively severe form of osteogenesis imperfecta due to a novel homozygous splicing mutation in FKBP10 (intron 8 c.1399+1G>A), which results in aberrant mRNA processing and consequent lack of FKBP65 chaperone. Although this mutation does not affect collagen type I post translational modifications in dermal fibroblasts, the histomorphometric pattern of our patient's bone sample showed a mineralization defect possibly due to the mutation in FKBP10. PMID- 22061864 TI - Bisphosphonates and glucocorticoid osteoporosis in men: results of a randomized controlled trial comparing zoledronic acid with risedronate. AB - BACKGROUND: We studied 265 men (mean age 56.4 years; range 18-83 years), among patients enrolled in two arms of a double-blind, 1-year study comparing the effects of zoledronic acid (ZOL) with risedronate (RIS) in patients either commencing (prednisolone 7.5 mg/day or equivalent) (prevention arm, n=88) or continuing glucocorticoid therapy (treatment arm, n=177). METHODS: Patients received either a single ZOL 5 mg infusion or RIS 5 mg oral daily at randomization, along with calcium (1000 mg) and vitamin D (400-1200 IU). Primary endpoint: difference in percentage change from baseline in bone mineral density (BMD) at the lumbar spine (LS) at 12 months. Secondary endpoints: percentage changes in BMD at total hip (TH) and femoral neck (FN), relative changes in bone turnover markers (beta-CTx and P1NP), and overall safety. FINDINGS: In the treatment subpopulation, ZOL increased LS BMD by 4.7% vs. 3.3% for RIS and at TH the percentage changes were 1.8% vs. 0.2%, respectively. In the prevention subpopulation, bone loss was prevented by both treatments. At LS the percentage changes were 2.5% vs. -0.2% for ZOL vs. RIS and at TH the percentage changes were 1.1% vs. -0.4%, respectively. ZOL significantly increased lumbar spine BMD more than RIS at Month 12 in both the prevention population (p=0.0024) and the treatment subpopulation (p=0.0232) in men. In the treatment subpopulation, ZOL demonstrated a significantly greater reduction in serum beta-CTx and P1NP relative to RIS at all time-points. In the prevention subpopulation, ZOL significantly reduced beta-CTx at all time-points, and P1NP at Month 3 (p=0.0297) only. Both treatments were well tolerated in men, albeit with a higher incidence of influenza-like illness and pyrexia events post-infusion with ZOL. INTERPRETATION: Once-yearly ZOL preserves or increases BMD within 1 year to a greater extent than daily RIS in men receiving glucocorticoid therapy. PMID- 22061866 TI - Changes of the vasculature and innervation in the anterior segment of the RCS rat eye. AB - Investigating the anterior eye segment vasculature and innervation of dystrophic RCS rats, two major unique findings were observed: in the iris, young adult animals with retinal dystrophy showed an increase in substance P nerve fibres and a dilation of arterioles and capillaries. This finding continued during ageing. In the pars plana region, the surface covered by venules decreased continuously with age. In older animals, this decrease was parallelled by a local decrease of sympathetic TH-positive nerve fibres supplying these venules. For both conditions, no comparable data exists so far in the literature. They might point to a unique situation in the anterior eye segment of the dystrophic RCS rat. PMID- 22061867 TI - Treatment differences in the therapeutic relationship and introject during a 2 year randomized controlled trial of dialectical behavior therapy versus nonbehavioral psychotherapy experts for borderline personality disorder. AB - OBJECTIVE: The present study explored the role of the therapeutic relationship and introject during the course of dialectical behavior therapy (DBT; Linehan, 1993) for the treatment of borderline personality disorder. METHOD: Women meeting DSM-IV criteria for borderline personality disorder (N = 101) were randomized to receive DBT or community treatment by experts. The Structural Analysis of Social Behavior (Benjamin, 1974) was used to measure both the therapeutic relationship and introject. RESULTS: Relative to community treatment by experts, DBT participants reported the development of a more positive introject, including significantly greater self-affirmation, self-love, self-protection, and less self attack, during the course of treatment and 1-year follow-up. The therapeutic relationship did not have an independent effect on intrapsychic or symptomatic outcome but did interact with treatment. DBT participants who perceived their therapist as affirming and protecting reported less frequent occurrences of nonsuicidal self-injury. CONCLUSIONS: The study showed positive intrapsychic change during DBT and emphasized the importance of affirmation and control in the therapeutic relationship. Results are discussed in the context of understanding the mechanisms of change in DBT. PMID- 22061868 TI - Investigation of mechanisms by which sodium citrate reduces the pink color defect in cooked ground turkey. AB - The principal mechanism by which sodium citrate reduces the pink color defect in cooked ground turkey was investigated. Sodium citrate (SC; 0, 0.125, 0.25, 0.5, 1.0, 2.0M), sodium nitrite (0.01, 0.1M), and nicotinamide (0.5, 0.75M) were combined in solutions of bovine hemin to determine SCs ability to bind heme iron and competitively inhibit pink-color-generating ligands from binding. Additionally, the effects of sodium erythorbate (0, 275, 550ppm), ferrous iron chloride (0, 0.3, 3.0, 30ppm), and ferric iron chloride (0, 0.3, 3.0, 30ppm) on SCs ability to reduce pink cooked color was examined. Absorbance curves of hemin+nitrite and hemin+nicotinamide were relatively unaffected by SC, therefore whether or not SC bound heme iron, that did not appear to be a mechanism for inhibiting the pink color defect. Both ferrous and ferric iron chloride had minimal effects on color values, possibly due to sodium tripolyphosphate chelation ability in the meat system and thus their presence did not enhance SCs ability to reduce the pink color defect. However, sodium erythorbate, a reducing agent, inhibited SCs ability to decrease the pink color defect in samples induced pink with sodium nitrite and nicotinamide. Therefore, it appears SC requires the presence of oxygen and may participate in oxidative processes to reduce the pink color defect. PMID- 22061869 TI - Instrumental evaluation of pH effects on ability of pork chops to bloom. AB - Color plays an important role in consumer purchase decisions of pork. For this reason, the objective of this study was to determine the usefulness of instrumental measures of bloom and bloom as a function of pH. Color was measured with two instruments on pork chops of varied ultimate pH (5.1-6.1) in a vacuum package and again after blooming. During bloom, Hunter a* increased while Minolta a values changed little. Bloom had no effect on either measure of lightness (L* or L). With bloom, Hunter Hue Angle decreased indicating an increase in red color, while Minolta Hue Angle measurement increased with bloom, implying a decrease in true red color. Although lightness was unaffected by bloom, pH had a significant effect on Hunter L* and Minolta L values. Increasing pH resulted in an increase of Hunter a*, but not Minolta a, in both unbloomed and bloomed chops. Hunter Hue Angle was consistently higher than Minolta Hue Angle regardless of bloom status or pH. PMID- 22061870 TI - Significance of storage time on degree of blooming and colour stability of pork loin from different crossbreeds. AB - The objective was to investigate the effect of ageing time (1 day vs. 8 days postmortem) and sire breed used in the crossbreed (Duroc sired vs. Landrace sired pigs) on blooming ability and colour stability of pork M. longissimus dorsi (LD). The colour was measured during blooming (0, 10, 30, 60, 90min and 24h after cutting) and during subsequent display (1, 2, 3 and 6 days) at 3 degrees C. The contents of deoxymyoglobin (Mb), oxymyoglobin (MbO(2)) and metmyoglobin (MetMb) were calculated. Ageing improved the blooming of LD from both crossbreeds with increased content of MbO(2) and decreased content of Mb, resulting in increased lightness, redness and yellowness. Ageing had smaller effect on colour stability with slightly lower MetMb in aged meat. Crossbreed affected both blooming and colour stability. LD from Landrace-sired pigs bloomed more than LD from Duroc sired pigs, but more MetMb was formed during subsequent storage, although at a low level in both crossbreeds. The present data show superior colour characteristics of fresh pork aged for 8 days. PMID- 22061871 TI - Significance of early postmortem temperature and pH decline on colour characteristics of pork loin from different crossbreeds. AB - The significance of early postmortem (pm) temperature and pH decline and the level of the muscle metabolites creatine phosphate (CP) and adenosine triphosphate (ATP) on the colour of porcine M. longissimus dorsi was studied in a factorially designed experiment. Two stress levels peri mortem (minimal stress vs treadmill exercise and electrical stunning of the pigs) and four genotypes (Duroc boars crossed with Landrace-Yorkshire sows vs. Hampshire-Duroc boars crossed with Landrace-Yorkshire sows, including carriers and non-carriers of the halothane and RN(-) genes, respectively) were included. Early pm muscle temperature and the accompanying pH decline had a significant influence on the pork colour independent of genotype. The combination of high temperature and low pH early pm increased lightness and yellowness, which is ascribed to inactivation of oxygen consuming enzymes and protein denaturation. The effect of early pm temperature and pH on pork redness was more complex. It appears to be closely related to the extent of heat generation, CP and ATP levels and pH immediately pm in the muscle, which influence the activity of oxygen-consuming enzymes. PMID- 22061872 TI - Influence of dietary creatine monohydrate and carcass cooling rate on colour characteristics of pork loin from different pure breeds. AB - Increased creatine content in the muscle may delay postmortem (pm) lactate formation and postpone pH decline, hence potentially affect the colour of pork. The influence of dietary supplementation with 0 or 50g creatine monohydrate (CMH)/d for 5 days prior to slaughter and two cooling rates of pig carcasses on the colour characteristics of pork loin from purebred Duroc and Landrace pigs was investigated. CMH increased the content of creatine phosphate in pork loin measured immediately following bleeding, delayed early pm pH decline and gave rise to less red and yellow colour, probably due to induction of a more pronounced oxidative muscle metabolism. A faster cooling rate pm induced darker and less yellow colour in loins from Duroc and Landrace pigs, while only loins from Landrace became less red. Loins from Duroc pigs were darker, less red and less yellow than loins from Landrace pigs, due to slower pH decline and a higher ultimate pH in these loins. Colour stability of pork loin during chill storage, measured as oxidation to metmyoglobin, was not affected by dietary CMH, cooling rate or pig breed. Consequently, the registered differences in colour between treatments during storage were merely due to the degree of initial blooming, and more attention to factors of importance for the degree of blooming should be in focus in future studies of factors of importance for meat colour. PMID- 22061873 TI - Effects of early maternal separation of lambs and rearing with minimal and maximal human contact on meat quality. AB - The present study aims to assess the effect of gentling on behaviour and meat quality of lambs. Thirty-two Comisana lambs were divided into four groups of eight animals: ER (ewe reared), AR (artificially reared) and the corresponding gentled groups ERG and ARG. The provision of human contacts stimulated gentled subjects to explore, whereas the proportion of idling subjects was reduced (P<0.10). At increasing age the number of subjects contacting the person increased in the gentled groups (P<0.05). Lambs left with their dams showed higher warm and cold carcass yields compared to artificially reared animals, although animals benefiting from both maternal care and gentling, had the highest dressing percentage (P<0.05). Values of pH declined more rapidly in meat from gentled animals than from ungentled subjects (P<0.05), b* and h values were higher in ARG than in AR group (P<0.05), whereas Warner-Bratzler shear force and hardness tended to be lower in gentled lambs (P<0.15). We conclude that human animal relationship can play an important role in affecting welfare, productive performances and meat quality of lambs, in particular when young subjects are prematurely separated from mothers. PMID- 22061874 TI - The effect of journey time and stocking density during transport on carcass and meat quality in rabbits. AB - Four hundred and fifty hybrid commercial rabbits (half males and half females) at the end of their productive cycle (82 days old) were transported in cages (98*52*24cm, length*width*height) at high or low density (75.5 or 49.0kg/m(2) - 15 or 10 animals per cage) on an uncovered truck for 1, 2 or 4h. Live weight before and after transport as well as slaughter data were recorded for each rabbit. A subset of 180 carcasses were evaluated for meat quality on the basis of meat pH, colour (CIELab system), cooking loss, drip loss and shear force. As a representative of the whole carcass muscle/bone ratio, the left hind leg was separated, dissected and its meat analysed in order to determine its water, protein, ash and lipid content. It was found that a longer journey significantly increases the live weight losses (3.3% vs. 2.0% vs. 1.6% for 4, 2 or 1h, respectively; P<0.001), as a result not only of urine and fecal losses, but also of a decrease in carcass weight (P<0.01) during transport. Ultimate pH (pH(u)) was higher and pH drop lower in rabbits transported for 4h compared to those transported for 2h (P<0.05). Moreover, the meat from animals that had undergone the longest journey was more purple-red (P<0.05), darker (P<0.0001), and firmer when raw and showed less cooking loss than meat from those that underwent shorter journeys. Transport density did not influence any of the considered parameters and there was no interaction between transport time and density. PMID- 22061875 TI - Protein and lipid oxidation in Longissimus dorsi and dry cured loin from Iberian pigs as affected by crossbreeding and diet. AB - Lipid and protein oxidation in Longissimus dorsi (LD) and dry-cured loins from pigs with different genetic (pure Iberian (IBP), Iberian female*Duroc male (IB*D) and Duroc female*Iberian male (D*IB)) and feeding backgrounds (free rearing on acorn and pasture (MON), concentrates high in oleic acid and supplemented with 250ppm of vitamin E(HOVE) and control concentrates (CON)) were investigated. Diet influenced the fatty acids profile from PL and alpha- and gamma-tocopherol contents of LD. IBP-MON pigs showed the lowest malonaldehyde (MDA) values at 200min of iron induced muscle oxidation. Dry-cured loins from IBP-HOVE pigs had significantly (p<0.05) higher values of TBARS than those from the other batches. Neither the diet nor crossbreeding affected hexanal counts in dry-cured loins. Protein carbonyl content showed a similar trend to that observed for MDA values in LD, suggesting a protective role of tocopherol against lipid and protein oxidation. The positive and significant correlations between iron induced lipid oxidation in LD (200 min) and carbonyl content in LD and dry-cured loin (R(2): 0.55 and R(2): 0.52, respectively, p<0.01) support the relationship between lipid and protein oxidation. PMID- 22061876 TI - Central nervous system tissue detection in meat from advanced meat recovery systems. AB - Three hundred meat samples, recovered from beef neck- and breast-bones using a conventional advanced meat recovery (AMR) system, the de-sinewed minced meat (DMM10) technology, and hand-boning, were collected and tested for presence of central nervous system tissue (CNST) in meat using an ELISA-based test. Samples were collected at two processing facilities (Est. A and B). Sternum meat was the non-CNST reference (control) - it is distant from brain and spinal cord locations on a carcass, with low likelihood of contamination with CNST. Neckbone meat was recovered from bones obtained from carcasses where the spinal cord was removed manually, Est. B, or using a Jarvis circular hydraulic cord remover saw, Est. A. All samples from AMR, DMM, and hand methods showed lower calculated levels of "risk material" than the stated limit of detection (0.1%) of ELISA kit. There was no apparent difference among these, and use of the Jarvis saw had no perceptible advantage. PMID- 22061877 TI - Eating quality of commercially processed hot boned sheep meat. AB - The aim of this work was to establish consumer perceptions of the eating quality of commercially processed hot boned sheep meat. The eating quality scores for tenderness, flavour, juiciness, and overall liking of grilled m. longissimus thoracis et lumborum (LL) were derived from untrained consumers. The animals used in this experiment were sourced from three different properties and were of various ages, breed, and sex, and had been on various quality pastures. All carcases were subjected to immobilisation, spinal discharge and high voltage electrical stimulation and boned within 2h of slaughter. All LL samples were frozen after boning according to the system applied at the abattoir and samples kept for consumer assessment and measurement of meat quality. The results showed, on average carcases entered rigor at high temperatures with a pH of 5.95 at 29.3 degrees C. With an average sarcomere length of 1.68MUm, some shortening was evident and there was a significant difference between lots in sarcomere length (P<0.05). A large percentage (82%) of samples had a pH greater than 5.8 at the time of freezing. All samples taken for shear force analysis exceeded a recommended threshold for acceptable table meat of 49N and there was no significant difference between lots (P>0.05). Only 13.5% of the samples met the 'good everyday' requirement following sensory assessment and there were significant differences between lots for eating quality traits (P<0.05). This work clearly shows that the application of effective electrical stimulation is not sufficient to ensure that hot boned sheep meat will be suitable as a table meat. These findings highlight the need for the inclusion of other intervention techniques. PMID- 22061878 TI - Prediction of intramuscular fat by impedance spectroscopy. AB - Multiple multi-frequency impedance measurements during the computer controlled passage of a probe through the M. longissimus dorsi in pork and beef were applied. It was expected that the variability in impedance would correlate with the intramuscular fat (IMF) due to the inhomogeneous distribution of electrolytes and fat. We conducted our experiments in pig carcasses at different, well defined times post-mortem in varying directions of puncture (Experiment 1) and predicted the intramuscular fat in pork and beef by regression (Experiment 2). The highest correlations were obtained in experiment 1 for parameters characterising the variability of the impedance 24h post-mortem and insertion of the probe through the back fat and muscle towards the body cavity (r=0.54-0.79, P<0.001). Both of these were chosen for the measurements in experiment 2. Regression for the prediction of IMF in pork and beef in experiment 2 resulted in R(2) values of 0.12 and 0.48, respectively; and in RMSE values of 0.67 and 0.64, respectively. The correlation between the predicted and the IMF analysed by n-hexane extraction or Near Infrared Transmission varied from 0.28 to 0.69 (P<0.001) depending on species and breed. A selection of the carcasses for high IMF (above a certain threshold) using the impedance measurements agreed poorly with the analysed IMF. Depending on the level of IMF within a breed, low IMF contents were often over predicted (3.4-92.7%) or high IMF contents were estimated as too low (0-80.9%). Breed specific regression equations could improve the accuracy. These data indicate that the selectivity of the impedance method in the configuration presented here is not yet sufficient for practical use. PMID- 22061879 TI - Zn-porphyrin formation in cured meat products: Effect of added salt and nitrite. AB - Zn-porphyrin (Zn-pp) was quantified by fluorescence spectroscopy in the cured and dry cured meat products: Parma ham, Iberian ham, dry-cured ham with added nitrite, cooked ham with added nitrite, raw ham meat, raw bacon and Karree-Speck. The highest amount of Zn-pp was found in dry-cured Parma ham and Iberian ham, while the use of nitrite as curing agent was found to inhibit completely the formation of Zn-pp in meat products. A positive correlation between both Zn content and Fe content and the logarithmic transformed Zn-pp content (measured as fluorescence intensity I(fl)) was found for the different cured and dry cured meat products, with correlation coefficients of 0.79 (p<0.001) and 0.71 (p<0.01), respectively. Log I(fl) correlates best with the Zn content, indicating that the formation of Zn-pp is proportional to the Zn content. A model system with vacuum packed pork in brine with different added levels of sodium chloride with or without nitrite and Zn acetate was investigated in order to further elucidate the mechanism of Zn-pp formation. Zn-pp increased with time (up to 42 days investigated) in non-cured meat and for meat cured solely with NaCl lower than 9%. Addition of nitrite or Zn(II) in the curing brine was found to inhibit formation of Zn-pp confirming the observations from the various cured meat products. It is suggested that a chloride anion assisted dissociation of iron from myoglobin could be rate-determining for Zn-pp formation in meat products. PMID- 22061880 TI - Drip loss of case-ready meat and of premium cuts and their associations with earlier measured sample drip loss, meat quality and carcass traits in pigs. AB - Drip loss of 374 samples taken from porcine M. longissimus dorsi and M. semimembranosus was measured by using the "bag method" (BM), EZ-DripLoss (EZ-DL) from premium cuts (PC) and in retail tray (case-ready meat; CRM). This provided a comparison between these methods and their relationships to other meat quality and carcass traits. Samples were prepared at 24h post-mortem (pm) and were measured 24 and 48h after preparation (at 48 and 72h pm) using the BM and after 48h (at 72h pm) with the EZ-DL and PC. Drip loss of meat kept in retail trays was measured after 7 days (CRM(7)) and daily within a week (CRM(1-7)). Average drip loss was 1.80% and 3.10% using the BM after 24 and 48h, respectively. EZ-DL and CRM(7) showed higher drip losses of 4.71% and 4.00%. Daily loss of CRM(1-7) showed a concavely shaped curve and increased from 1.57% to 5.64% after 7 days. High correlations were obtained between drip loss of CRM(7) and BM (r=0.88) or the EZ-DL (r=0.91). The development of drip loss in case-ready meat fitted by linear-quadratic regression (y=0.439+1.245x-0.072x(2)) showed that high drip loss measured earlier by bag and EZ-DripLoss methods was highly associated with a high intercept (r=0.63-0.72), a high linear increase (r=0.77-0.81), but larger decrease in increments (r=-0.82 to -0.86) during weekly stored meat in retail trays as supplied at consumer level. Because the positive linear regression coefficient was substantially higher than the negative quadratic regression coefficient, the development of drip loss is mainly dependent on the initial drip loss. Therefore, animals with high drip loss within 72h post-mortem also showed undesirable high drip loss curves over the entire retail period. Relationships between drip loss and other meat quality traits were similar for BM, EZ-DL and CRM(7). Of these the correlation between pH(24) and drip loss was highest with r= 0.54, -0.49 and -0.47 for BM, EZ-DL and CRMH(7), respectively. Interestingly, a correlation of r=-0.35 between blood pH value and CRML(7) was obtained. Carcass traits such as loin, ham, shoulder, belly weight or loin eye area showed only marginal correlations to drip loss. In conclusion, EZ-DL was the most appropriate method to predict drip loss of case-ready meat in retail trays and its development during a 7 day storage period. PMID- 22061881 TI - Effect of meat appearance on consumer preferences for pork chops in Greece and Cyprus. AB - The effect of meat appearance on consumers' preferences for pork chops was assessed using images manipulated for appearance characteristics. Data were collected from 412 consumers in Greece and Cyprus. Consumers were asked for their preference for pork chops from a book of computer-modified images and then completed a questionnaire of socio-demographic information, including eating and purchasing behaviour. Consumers under the age of 35 years showed preferences for dark red, lean pork, while consumers aged 35 years and older preferred either dark or light red pork. Gender appeared to be an important selection factor as men showed an increased preference for dark red pork while women preferred the light red. Consumers who stated that they like pork for its taste (91%) preferred either dark or light red pork chops while those who like pork for reasons other than taste preferred dark red, lean pork. Urban consumers preferred light red, fatty pork chops while the rural consumers preferred the dark red pork chops. PMID- 22061882 TI - Influence of muscle type on rheological properties of porcine myofibrillar protein during heat-induced gelation. AB - The gelation characteristics of myofibrillar proteins are indicative of meat product texture. Defining the performance of myofibrillar proteins during gelation is beneficial in maintaining quality and developing processed meat products and processes. This study investigates the impact of pH on viscoelastic properties of porcine myofibrillar proteins prepared from different muscles (semimembranosus (SM), longissimus dorsi (LD) and psoas major (PM)) during heat induced gelation. Dynamic rheological properties were measured while heating at 1 degrees C/min from 20 to 85 degrees C, followed by a holding phase at 85 degrees C for 3min and a cooling phase from 85 to 5 degrees C at a rate of 5 degrees C/min. Storage modulus (G', the elastic response of the gelling material) increased as gel formation occurred, but decreased after reaching the temperature of myosin denaturation (52 degrees C) until approximately 60 degrees C when the gel strength increased again. This resulted in a peak and depression in the thermogram. Following 60 degrees C, the treatments maintained observed trends in gel strength, showing SM myofibrils produced the strongest gels. Myofibrillar protein from SM and PM formed stronger gels at pH 6.0 than at pH 6.5. Differences may be attributed to subtle variations in their protein profile related to muscle type or postmortem metabolism. Significant correlations were determined between G' at 57, 72, 85 and 5 degrees C, indicating that changes affecting gel strength took effect prior to 57 degrees C. Muscle type was found to influence water holding capacity to a greater degree than pH. PMID- 22061883 TI - Impact of muscle type and sodium chloride concentration on the quality, sensory, and instrumental color characteristics of solution enhanced whole-muscle beef. AB - Beef biceps femoris (n=10; muscle sections, n=20; BF), infraspinatus (n=10; muscle sections, n=20; IS), and longissimus (n=10; muscle sections, n=20; LM) muscles were utilized to evaluate the effect of enhancement with phosphate and varying levels of sodium chloride in beef muscles differing in composition and palatability. Muscles were untreated or solution enhanced to 112% of raw product weight with sodium tripolyphosphate at 0.4% of product weight (STPP), or STPP and sodium chloride (NaCl) at 0.5%, 1.0% or 1.5% of product weight. There was a quadratic relationship (P=0.04) for percent free water to decrease and a linear relationship (P<0.01) for cook yield to increase as the level of NaCl increased. The IS steaks required less (P<0.05) shear force than either the BF or LM, with the BF and LM having similar (P>0.05) shear force values. There was a linear relationship (P<0.01) for shear force values to decrease with increasing salt concentration. Steaks from all four enhancement treatments had lower (P<0.05) shear force values than untreated steaks. Sensory overall tenderness ratings revealed that the IS and LM were similar (P>0.05) and superior (P<0.05) to the BF in tenderness. Steaks enhanced with STPP and 0.5%, 1.0%, or 1.5% NaCl all were rated more tender (P<0.05) than untreated or STPP-only treated steaks. The BF exhibited the lowest (P<0.05) L* (lightness) and a* (redness) values, as well as decreased (P<0.05) vividness. The LM generally exhibited superior color to the other two muscle types. There was a linear relationship (P<0.01) for L*, a*, b* (yellowness) values, and vividness to decline with increasing salt concentration, but steaks enhanced with STPP and 0.5% NaCl were similar (P>0.05) in a* values and vividness to untreated steaks. These results suggest that across three different muscles varying in composition and palatability, enhancement with 0.4% STPP and 0.5% NaCl allowed for improvements in palatability while minimizing the color deterioration associated with phosphate/salt enhancement. PMID- 22061884 TI - Antioxidant and modified atmosphere packaging prevention of discoloration in pork bones during retail display. AB - The objective of this study was to evaluate the ability of antioxidants to prevent discoloration in pork rib bones. Pork rib bones were removed from carcasses, frozen (-20 degrees C, 24h), split lengthwise, exposed to antioxidant solutions (ascorbic acid, citric acid, propyl gallate or ascorbic/EDTA mix), packaged (modified atmosphere [80% O(2) and 20% CO(2)] or air), then displayed in a retail case at 4 degrees C for 8days. Dark pigment formation was visually evaluated during the display period. Instrumental color was determined at the end of the 8-day display period. Visual bone discoloration increased over time for all treatments. After 2days of display, samples treated with propyl gallate were visually redder, less discolored and less green/black than samples treated with other antioxidants. After 8days of display, propyl gallate-treated samples had higher a* and b* values, as well as chroma (intensity). However, this difference was no longer large enough to be visually detected. PMID- 22061885 TI - Effects of feeding strategy during a short finishing period on performance, carcass and meat quality in previously-grazed young bulls. AB - Twenty-one Brown Swiss*Limousin young bulls reared on pasture were housed for a short finishing period (60 days). CA group (concentrate-ad libitum group) received concentrate and straw ad libitum for the whole finishing period. CR group (concentrate-restricted group) received 4kg of concentrate/animal per day and ad libitum alfalfa hay throughout the 60days. CRA group (concentrate restricted/ad libitum group) received the same diet as CR group for the first 30days and the same diet as CA group for the last 30days. CA and CRA groups presented higher fatness values. Myoglobin concentration in muscle was highest in CA group (P<0.05) and carotene content in subcutaneous fat was highest in CR group (P<0.01), while Warner-Bratzler shear force and sensory traits were unaffected (P>0.05). It is concluded that, in this type of young animal, 4kg concentrate plus ad libitum alfalfa hay for a 60-day finishing period, despite lower fatness, provides carcasses and meat with acceptable quality characteristics, similar to those obtained from ad libitum fed animals for the same period. PMID- 22061886 TI - Nutritional and sensory properties of dry fermented sausages enriched with n-3 PUFAs. AB - Enrichment of dry fermented sausages with n-3 fatty acids through a partial substitution of pork backfat by deodorised fish oil resulted in improved nutritional properties with regard to conventional sausages, without affecting sensory properties and oxidation status. The developed products supplied 0.64g EPA/100g and 0.46g DHA/100g product, and showed PUFA+MUFA/SFA ratio of 1.76 and n 6/n-3 ratio of 2.97. No signs of oxidation were found in any type of sausages, control and modified. None of the dienals and trienals reported as secondary lipid oxidation products and typical for fish oil were detected in the modified sausages. Instrumental colour differences were detected, however, without relevance in the sensory analysis. The sensory evaluation panel did not find differences in general acceptability. The modified dry fermented sausages can be considered a technologically viable functional food. PMID- 22061887 TI - Sensory properties of hot-deboned ostrich (Struthio camelus var. domesticus) Muscularis gastrocnemius, pars interna. AB - Cold-deboning is currently practiced in South African ostrich abattoirs. However, the advantages of hot-deboning include the reduction of costs and time, but there is always the risk of cold-shortening. The effects of hot-deboning of ostrich M. gastrocnemius, pars interna on meat sensory attributes were investigated. The data showed that the hot-deboned muscles' pH(48) (6.57+/-0.18) was significantly negatively correlated (r=-0.7813; P<0.038) to the mean Warner-Bratzler shear force values (71.28+/-18.62N, 12.7mm(-1) diameter) and positively correlated (r=0.789; P<0.035) to the mean scores for taste panel tenderness (66.39+/-15.45). After storage for 48h post-mortem, the hot-deboned muscles were found to be less juicy (P<0.004) and, according to both sensory tenderness scores and Warner Bratzler shear force values, tougher (P<0.0001) than the cold-deboned muscles. PMID- 22061888 TI - Pump rate and cooked temperature effects on pork loin instrumental, sensory descriptive and consumer-rated characteristics. AB - Fresh pork loins (n=15; muscle sections, n=30) were utilized to evaluate the effects of pump rate (0%, 6%, or 12%) with a solution of sodium tripolyphosphate and sodium chloride (0.4% and 1.0% targeted final product concentrations, respectively), and cooked endpoint internal temperature (71 or 82 degrees C) on instrumental texture, descriptive sensory profiles and consumer acceptance. Loins enhanced at a 12% pump rate had a higher (P<0.05) pH than untreated loins. While there were no differences in Warner-Bratzler shear force due to cooked endpoint temperature, chops enhanced at a 12% pump rate had lower (P<0.05) shear force values than untreated chops. Additionally, chops enhanced at 6% or 12% pump rates had lower (P<0.05) razor shear force values than untreated chops. Descriptive sensory analyses revealed that chops cooked to 71 degrees C had a more intense (P<0.05) blood serum flavor than chops cooked to 82 degrees C. Consumers found chops cooked to 82 degrees C to have a more acceptable overall flavor than chops cooked to 71 degrees C. Untreated chops had less intense (P<0.05) pork fat flavor, and more intense (P<0.05) blood serum, livery, and cardboard or oxidized flavor characteristics than chops enhanced at 6% or 12% pump rates. Additionally, sensory panelists reported chops enhanced at 6% or 12% pump rates to generally be more tender than untreated chops. Consumers reported a higher (P<0.05) overall acceptability for chops enhanced at 6% or 12% pump rates. Furthermore, both sensory panelists and consumers reported chops enhanced at 6% or 12% pump rates to be similar (P>0.05) in juiciness, regardless of endpoint temperature. However, untreated chops cooked to 82 degrees C were less juicy (P<0.05) than untreated chops cooked to 71 degrees C, suggesting retained palatability when enhanced chops are cooked to more abusive temperatures. PMID- 22061889 TI - Thermal inactivation of the frozen thawed traditional meat starter culture, Pediococcus pentosaceus, in a meat model system. AB - The equation, y((t))=y((0))e(kt), was fitted (R=0.9281, 0.9220 and 0.9117, respectively) to thermal inactivation data (55, 60 and 65 degrees C) of the traditional meat starter culture Pediococcus pentosaceus (10(7)cfu/ml) in a meat model system. The population reduction constant ('k') increased (about 2.5- and 3 fold) with an increase in the treatment temperature (from 55 to 60 degrees C and from 60 to 65 degrees C, respectively). The Q(10) (55-65 degrees C) for 'k' was 7.63. Thermal treatments of 19.1, 9.0 and 3.1min (55, 60 and 65 degrees C, respectively) reduced the population of P. pentosaceus by 2.0 logs. The value of 'k' and the duration of the thermal treatment played an important role in the extent of the inactivation of the culture. The "zero inactivation" temperature (T(0)) for P. pentosaceus was 49.9 degrees C. About 5 logs of the culture would be destroyed at 63 and 68 degrees C within about 15.5 and 6.5min, respectively. PMID- 22061890 TI - Accelerated processing of dry-cured ham. Part I. Viability of the use of brine thawing/salting operation. AB - In a previous study, the brine thawing/salting operation using frozen hams as raw material was proposed in order to obtain accelerated processing of dry-cured hams. The time needed to reach the same NaCl concentration on a dry weight basis and the same NaCl concentration in the ham liquid phase for the deeper areas at the end of the post-salting stage were determined. The aim of this work was to study the influence of the brine thawing/salting operation on the whole dry-cured ham manufacturing process, using the traditional thawing and salting methods as control. The obtained results indicate that although a strong reduction in the thawing, salting and post-salting stages is obtained by using brine thawing/salting, the time needed in the dry-curing and maturing phases increases compared to those traditionally processed, probably due to the absence of pile salting and thus the reduction in the thickness of the ham piece as a consequence of the ham pressing. From the composition and microbiological point of view, no significant differences were observed among the hams processed by the different treatments. PMID- 22061891 TI - Accelerated processing of dry-cured ham. Part 2. Influence of brine thawing/salting operation on proteolysis and sensory acceptability. AB - In a previous study, the brine thawing/salting operation using frozen hams as raw material was studied as a valid alternative for the accelerated processing of dry cured hams. But no information was available on how this treatment could affect some important biochemical mechanisms and the sensory quality of hams. The aim of this work was to study the influence of the simultaneous brine thawing/salting operation on proteolysis and sensory acceptability of the produced dry-cured hams. The results confirm that dry-cured hams can be produced by using brine thawing/salting with a substantial reduction in the thawing and salting time needed. This accelerated process resulted in similar or even better sensory preferences than hams produced through the traditional method. However, the preference of consumers based on the appearance was lower for most of the hams than when using the traditional method, probably due to a wider slice section of the brined hams that can be corrected by adequate pressure during the salting. Thus, this treatment can be used without affecting the quality of dry-cured hams. PMID- 22061892 TI - Effects of transport time and season on aspects of rabbit meat quality. AB - The aim of this study was to determine whether transport times of up to 7h can have a significant effect on instrumental meat quality traits in rabbits. Spain has very hot summers and cold winters; therefore, we performed replicates in two seasons. To evaluate the effect of transport time and season on rabbit meat quality, we assessed four meat quality parameters: pH, water holding capacity (WHC), texture (compression and Warner-Bratzler analyses), and colour (CIEL*a*b*). We also considered the effect of the position of the animals on the transport vehicle. After slaughter, we analysed steaks of Longissimus dorsi from all transported animals (n=216). Average pH at 24h and WHC did not differ significantly between transport time treatments. Position on the vehicle did not influence the measures of meat quality. Transport time had a significant effect on all the meat texture parameters measured by compression, but did not affect shear force or toughness. Transport time influenced a* but not L* or b*. Transport time had much less of an effect on meat quality than time of year; therefore the effect of season appeared to be independent of transport time. Position on the vehicle had no effect on meat quality. Based on our results, we conclude that the transport process can affect instrumental meat quality. PMID- 22061893 TI - Fatty acids, cholesterol and protein content of nutria (Myocastor coypus) meat from an intensive production system in Uruguay. AB - This study describes the total lipids, protein and fatty acids in the meat, liver, brain and adipose tissue of five male and five female nutria (Myocastor coypus). The animals were reared on a specialized farm in Uruguay. Total lipid content was between 1.41% and 1.84% in males and females. Total cholesterol content was between 70.1mg and 72.7mg/100g of wet tissue. The protein content was between 19.56% and 22.34% in males and females. No significant differences (P>0.05) were detected between males and females for total lipid, cholesterol or protein. Total, saturated, monounsaturated and polyunsaturated fatty acid values were higher (P<0.001) in female than in male thigh muscle. Pectoral muscle had more (P<0.05) saturated and monounsaturated fatty acids in females than in males. Subcutaneous adipose tissue from females had the highest (P<0.01) total, saturated and monounsaturated but not polyunsaturated fatty acids while abdominal adipose tissue from males had more polyunsaturated fatty. PMID- 22061894 TI - Physicochemical and sensory properties of chicken nuggets with washed mechanically deboned chicken meat: Research note. AB - The effects of different proportions (0%, 10%, 20%, 30%, 40%) of washed mechanically deboned chicken meat (WM) as a substitute for hand deboned chicken meat, on the physicochemical and sensory characteristics of chicken nuggets were evaluated. The addition of WM increased fat content, but it was only significant (P<0.05) when 40% of WM was added, whereas the protein content was significantly (P<0.05) reduced as from 20%. Significant differences (P<0.05) were found in L(*), a(*) and b(*) values with different proportions of WM, however, these differences were evidently not discerned as shown by the no significant differences (P>0.05) in DeltaE(*) color scores. The addition of WM did not affect (P>0.05) sensory attributes of chicken nuggets. From a technical viewpoint, up to 40% WM could be incorporated into nugget formulation instead of hand deboned chicken meat without affecting sensory attributes of the product. Minor changes in composition were observed but they were probably not detrimental to the product. PMID- 22061895 TI - Differential scanning calorimetry of porcine adipose tissues. AB - Differential scanning calorimetry (DSC) was used for the direct analysis of melting properties in porcine subcutaneous, intermuscular, and kidney leaf adipose tissue by heating at a constant ratio of +5 degrees C/min from 4 to 90 degrees C. Melting curves for adipose tissues as well as fat extracted from the associated tissues by chloroform-methanol were generated using DSC. Major peaks in DSC curves were similar among types of adipose tissue but the temperatures of the melting peak and conclusion point differed among types of adipose tissues. From the visual appearance of fat samples it appeared that the major DSC peak corresponded to phase transition of the fat. The direct DSC analysis of porcine adipose tissues may be useful to determine melting properties. PMID- 22061896 TI - Sodium nitroprusside may modulate Escherichia coli antioxidant enzyme expression by interacting with the ferric uptake regulator. AB - Efforts to explore possible relationships between nitric oxide (NO) and antioxidant enzymes in an Escherichia coli model have uncovered a possible interaction between sodium nitroprusside (SNP), a potent, NO-donating drug, and the ferric uptake regulator (Fur), an iron(II)--dependent regulator of antioxidant and iron acquisition proteins present in Gram-negative bacteria. The enzymatic profiles of superoxide dismutase and hydroperoxidase during logarithmic phase of growth were studied via non-denaturing polyacrylamide gel electrophoresis and activity staining specific to each enzyme. Though NO is known to induce transcription of the manganese-bearing isozyme of SOD (MnSOD), treatment with SNP paradoxically suppressed MnSOD expression and greatly enhanced the activity of the iron-containing equivalent (FeSOD). Fur, one of six global regulators of MnSOD transcription, is uniquely capable of suppressing MnSOD while enhancing FeSOD expression through distinct mechanisms. We thus hypothesize that Fur is complacent in causing this behaviour and that the iron(II) component of SNP is activating Fur. E. coli was also treated with the SNP structural analogues, potassium ferricyanide (PFi) and potassium ferrocyanide (PFo). Remarkably, the ferrous PFo was capable of mimicking the SNP-related pattern, whereas the ferric PFi was not. As Fur depends upon ferrous iron for activation, we submit this observation of redox-specificity as preliminary supporting evidence for the hypothesized Fur-SNP interaction. Iron is an essential metal that the human innate immune system sequesters to prevent its use by invading pathogens. As NO is known to inhibit iron-bound Fur, and as activated Fur regulates iron uptake through feedback inhibition, we speculate that the administration of this drug may disrupt this strategic management of iron in favour of residing Gram-negative species by providing a source of iron in an otherwise iron-scarce environment capable of encouraging its own uptake. However, these gains may be counteracted by the oxidative consequences of iron and NO, as the former can catalyse the formation of toxic free radical species while the latter can inhibit enzymes and contribute to the formation of other toxic compounds. The potential consequences of SNP on microbial growth warrant future investigation. PMID- 22061897 TI - Utilization of microbes to process and preserve meat. AB - This paper discusses how, and to what extent, the addition of microorganisms to meats helps to meet the needs of consumers and industry. Lactic acid bacteria adapted to meats improve the safety of fermented sausages by means of acid formation. Using selected strains, the safety of certain non-fermented, perishable meat products may be improved without affecting their shelf life. Certain bacteriocin-forming cultures may reduce the levels of Listeria monocytogenes in some meat products significantly, but their effect on the overall safety of meats is limited by the resistance of Gram-negative bacteria. Data on the effect of microorganisms on the sensory properties of fermented meats are summarized. For bacteria to have a probiotic effect, they need to attain high numbers during fermentation and/or storage of meats. Genetic engineering of cultures may improve certain properties of the strains but benefits to consumers and industry are too small to make them acceptable by consumers and regulatory bodies in the near future. PMID- 22061898 TI - Castration and slaughter age effects on panel assessment and aroma compounds of the "mestico" goat meat. AB - Cooked meat from castrated male and intact "mestico" goats slaughtered at 175, 220, 265 and 310 days of age, were analysed by panellists and GC-MS. Slaughter age had a (P<0.05) effect on organoleptic qualities of goat meat. Scores for sensorial attributes were not different (P<0.05) for intact and castrated goats. A total of 87 compounds were identified and a further 21 were partially characterized by GC-MS. Hydrocarbons were presented in the highest relative amounts and all aroma isolates were dominated by products of lipid degradation. Total relative abundance of volatiles was identified at higher levels in the cooked meat from castrated goats than from entires. Meat from goats slaughtered at first age (175 days) was preferred by panellists and was found to have the lowest number of volatiles and total relative abundance. PMID- 22061899 TI - Effect of pelvic suspension on three major leg muscles in the pig carcass and implications for ham manufacture. AB - Thirty-two female pigs were slaughtered and their left sides suspended conventionally by the Achilles tendon whilst right sides were suspended from the pelvic bone. The first 16 pigs were used to measure suspension effects on the characteristics of three major leg muscles (m. gluteobiceps, m. semimembranosus and m. rectus femoris) and to assess their suitability for ham manufacture. The remaining pigs were used for the production of hams, made from tunnel- boned whole legs injected to a target 10% weight gain, then tumbled and cooked. Compared with conventional hanging, pelvic suspension resulted in significantly (P<0.01) lower weight loss from the sides during chilling (2.8 and 2.5%). There were major changes in the shape of all three muscles, with pelvic suspension producing marked increases in the width of the m. gluteobiceps (24%) and length of the m. semimembranosus (34%), and a small reduction in the length of the m. rectus femoris (2%). It also resulted in the two former muscles having a relatively higher brine retention, lower drip losses after storage and lower instrumental texture values (Volodkevitch shear force). Cooking loss was reduced in the pelvic-suspended m. semimembranosus. Similarly, whole gammon hams made from pelvic-suspended sides had greater injection gains than hams from conventionally-hung sides (13.6 and 12.3%), with lower cooking losses (16.7 and 19.0%). Instrumental texture values (punch and die peak force) made on the individual muscles in 3-mm thick slices were lower for the m. gluteobiceps (5914 and 9085 g) and m. semimembranosus (6163 and 7600 g) as a result of pelvic suspension. There were minor but significant effects on some colour parameters which probably have little commercial impact. The results demonstrate the advantages of pelvic suspension in terms of brine uptake and retention, and hence increased yield, as well as reduced toughness, for at least two of the major leg muscles, m. gluteobiceps and m. semimembranosus, with no disadvantage for the m. rectus femoris. Together, these three muscles constitute about half of the trimmed leg weight. PMID- 22061900 TI - In vivo assessment of the quantity of breast muscle by sonography in broilers. AB - Two experiments were conducted to estimate the amount and yield of breast meat in living chickens by sonography. Results from the first experiment showed that the use of some cross-sectional areas (CSAs) of the breast muscles (Pectoralis major and Pectoralis minor, PM) in combination with the body weight (BW) value could be used to predict breast muscle and yield. Values of the coefficient of determination (r(2)) were near 0.90 and 0.65 for the amount and yield of breast meat respectively. Accurate results were obtained by the combination of three chosen (among more than 40) CSAs of the PM muscle. In the second experiment, the use of the CSAs was limited to the three most explicative ones defined in the first experiment. This experiment was conducted with a larger number of animals and confirms that it is possible to predict in vivo the amount and yield of breast meat with a good accuracy in chickens. PMID- 22061901 TI - Initial chilling rate of pre-rigor beef muscles as an indicator of colour of thawed meat. AB - The effect of three rigor temperatures and two muscles of different fibre composition on the colour of thawed meat were determined. Within 45 min post mortem, m. semitendinosus (ST) and m. biceps femoris (BF) from unstimulated heifer sides were held at 0, 10 and 35 degrees C until they entered rigor. The rate of pH fall was higher at 35 degrees C than at 0 and 10 degrees C; and the pH values were lower (first 12 h post mortem) in the ST than the BF. Hunter L*, a* and b* and the hue angle increased with increasing rigor temperature (P<0.001). The ST was lighter and yellower and had greater hue angle than the BF. Colour parameters were plotted against the rate of muscle cooling in the first hour post mortem and linear regression lines were fitted to the data and equations were derived that gave a good indication of the colour and colour stability of the muscles as meat. PMID- 22061902 TI - Microbiological contamination of raw beef trimmings and ground beef. AB - To survey the microbiological quality of beef trimmings and final-ground beef, samples were collected from eight commercial grinding facilities, including trimmings from fed-cattle, culled-beef cows, culled-dairy cows, imported-beef trimmings and finished-ground products. Trim samples (core and purge) and ground product samples (n=586) were evaluated for aerobic plate (APC), total coliform (TCC), Escherichia coli (ECC) and Staphylococcus aureus counts and the presence of Salmonella spp. and Listeria monocytogenes. As fat content in the trimmings increased, APC also increased. Trimmings from fed-cattle had higher (P<0.05) APC and TCC than trimmings from culled-beef cows, culled-dairy cows and imported trimmings. Purge samples produced higher (P<0.05) APC, TCC and ECC than core samples, but there were no difference (P>0.05) across fat percentages in APC, TCC, ECC or S. aureus counts. Final-ground beef samples had a 13.6 and 1.5 % incidence of L. monocytogenes and Salmonella spp., respectively. The results of this study indicate specific areas of potential that ground beef processors could capitalize upon to further improve the microbiological quality of their finished product. Ground beef processors should focus their efforts on reducing the microbial counts on incoming raw materials, especially those containing large proportions of subcutaneous fat, and processors should no longer incorporate the purge component of raw materials into ground beef. From this study, it is also apparent that ground beef processors should implement sanitation and manufacturing procedures that address L. monocytogenes contamination. PMID- 22061903 TI - Estimation of poultry breastmeat yield: magnetic resonance imaging as a tool to improve the positioning of ultrasonic scanners. AB - Magnetic resonance imaging (MRI) was used to reconstruct three-dimensional breast muscle volume of 30 broilers and to locate the most suitable cross-sections to estimate breast muscle yield by ultrasonic scanner. The high accuracy of the determination of the breast muscle yield (R(2)=0.92) from the volume calculated by the sum of 6 mm-spaced MRI transverse images justified the choice of MRI as a reference method. Treatment of the images showed that it was possible to obtain acceptable breast meat yield prediction by MRI from a combination of two or three muscle transverse cross-section area measurements. It also showed that the need to find interfaces reflecting ultrasound is a considerable handicap for optimizing the ultrasonic technique. The oblique echotomographic plane crossing the coracoid bone lengthwise and the fore part of the breast bone appears to be the most appropriate to improve significantly the determination provided by the transverse image situated at the fore part of the breast bone. PMID- 22061904 TI - In situ transesterification of fatty acids from Iberian pig subcutaneous adipose tissue. AB - The purpose of this study was to optimize a rapid method for fatty acid analysis in Iberian pig subcutaneous adipose tissue. An in situ transesterification method was used to avoid the lengthy lipid extraction step. Samples were in situ transesterified with 5% HCl/methanol at 70 degrees C, and toluene was used to help dissolve lipids. The method had advantages over other in situ methods since only 45 min were required to completely transesterify the fatty acids, and 10 min to obtain the fatty acid profile. A sample size of 25 mg of adipose tissue was suitable. The in situ transesterification gave higher fatty acid concentrations than conventional lipid extraction and transesterification, the differences being significant for all the fatty acids. Relative fatty acid contents were similar to those found by the conventional method. PMID- 22061905 TI - Proteolytic specificity of cathepsin D on bovine F-actin. AB - Proteolysis of bovine F-actin by cathepsin D (E.C. 3.4.23.5) in 50 mM Na acetate buffer, pH 5.5, at 37 degrees C was investigated using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and reverse-phase high performance liquid chromatography (RP-HPLC). Actin was hydrolyzed by cathepsin D during incubation to peptides detectable by RP-HPLC, although no degradation products were detected by SDS-PAGE. Peptides (2% trichloroacetic acid-soluble) from the hydrolyzate were isolated by RP-HPLC on a C(18) column using an acetonitrile/water gradient and identified from their N-terminal sequence and mass. Cathepsin D cleavage sites were identified at Cys(12)-Asp(13), Gly(22) Phe(23), Arg(30)-Ala(31), Thr(79)-Asn(80), Ile(87)-Trp(88), Thr(91)-Phe(92), Phe(92)-Tyr(93), Arg(97)-Val(98), His(103)-Pro(104), Leu(107)-Thr(108), Thr(108) Glu(109), Lys(120)-Met(121), Leu(144)-Tyr(145), Ile(153)-Val(154), Leu(155) Asp(156), Ile(167)-Tyr(168), Leu(180)-Asp(181), Met(192)-Lys(193), Leu(195) Thr(196), Arg(208)-Glu(209), Arg(212)-Asp(213), Leu(223)-Asp(224), Lys(240) Ser(241), Thr(262)-Leu(263), Trp(342)-Ile(343), Arg(349)-Ser(350), Trp(358) Ile(359), and Lys(375)-Cys(376). In general, cathepsin D preferentially cleaved bonds containing at least one hydrophobic amino acid residue. The results of this study showed that actin was degraded extensively by cathepsin D with peptides released from numerous locations in the protein molecule. PMID- 22061906 TI - Meat quality of steers finished on autumn grass, grass silage or concentrate based diets. AB - The objective of this experiment was to determine the effect of varying the proportions of autumn grass and concentrates and grass silage and concentrates on the quality of meat from cattle with similar rates of carcass growth. Fifty continental crossbred steers were assigned to five treatments. The experimental diets offered were (1) grass silage ad libitum plus 4 kg concentrate (SC), (2) 1 kg hay plus 8 kg concentrate (CO), (3) 6 kg grass dry matter (DM) plus 5 kg concentrate (CG), (4) 12 kg grass DM plus 2.5 kg concentrate (GC) and (5) 22 kg grass DM (GO). The experiment lasted 85 days after which all animals were slaughtered. The right side m. longissmus dorsi was excised from all animals 24 h post slaughter for assessment of meat quality. Treatments SC and CO resulted in animals with whiter (P<0.05) subcutaneous and kidney/channel fat than all other treatments. There was an interaction (P<0.05) between ageing time and treatment with treatment GC having higher (P<0.05) tenderness, texture and acceptability values after 2 days ageing, but not after 7 or 14 days ageing. It is concluded that supplementing grass with low levels of concentrate produced the most tender and acceptable meat at 2 days post mortem, but that further ageing eliminated all treatment effects on eating quality of beef. PMID- 22061907 TI - Effect of fat content and soy protein/carrageenan mix on the quality characteristics of comminuted, scalded sausages. AB - The effects of soy protein concentrate and kappa-carrageenan mix (GELPRO, 3:1 ratio) (ranging from 0 to 3%) and varying levels of collar fat (ranging from 20 to 40%) on comminuted scalded sausage quality characteristics were investigated. Sausage quality was determined by measuring textural, hydration and colour characteristics. GELPRO preparate addition favourably affected WHC and thermal stability of sausages processed regardless of the fat content. Use of an additive affects the sausage texture, but the effect depends on the amount of the additive used. Fat reduction resulted in a decrease in hardness, gumminess and chewiness of final products. Lower fat contents were also accompanied by a significant reduction in the cooking yield and WHC. Sausage colour parameters were affected only by varying fat levels (L*, b*). PMID- 22061908 TI - Hamburger meat identification by dot-ELISA. AB - The use of low cost meats to adulterate meats and meat products has been reported. Appropriate methods of analysis then are needed in order to detect this practice. The dot-ELISA method was used to identify the meat of different animal species and to detect adulteration of hamburgers. Antisera to bovine, chicken, swine and horse albumin were produced and they could detect the meat extract of the homologous species at concentrations as low as 0.6%. Thus, the anti-albumin antisera could identify bovine, chicken, swine and horse meat with adequate specificity and sensitivity both in isolation and when added to hamburger. Commercial samples of bovine, chicken and swine hamburgers showed no adulteration with bovine, chicken, swine or horse meats. Our expectation of hamburger adulteration was not confirmed. PMID- 22061909 TI - A potential index for assessing the tenderness of hydrodynamic pressure (HDP) treated beef strip loins. AB - The objective of this research was to obtain physicochemical data that might prove useful in understanding the effect of hydrodynamic pressure (HDP), shock wave treatment on the structural and functional properties of the HDP-treated beef strip loins. A homogenization protocol that was sufficiently harsh to break up the tissue yet sufficiently gentle to maintain the integrity of the remaining subcellular structures was therefore developed for HDP-treated beef strip loins. Physicochemical changes resulting from HDP-treatment revealed a relationship between shear resistance value (tenderness level) and protein distribution. The 10,800*g pellet of homogenized HDP-treated strip loins showed a decrease in the protein content associated with a decrease in shear resistance values (increased tenderness). Conversely, the soluble-fraction (post 48,200*g) showed an increase in protein content as the shear resistance value decreased (tenderness increased) from ~11 to 6 kg. The data presented herein indicate that there is a relationship between the tenderness of hydrodynamic pressure (HDP) treated meat and the protein distribution in the HDP-treated samples. PMID- 22061910 TI - Quality characteristics of pork patties irradiated and stored in different packaging and storage conditions. AB - Patties were made from pork loin, individually vacuum- or aerobic-packaged and stored either at 4 or -40 degrees C. Refrigerated patties were irradiated at 0, 1.5, 3.0 or 4.5 kGy absorbed dose, and frozen ones were irradiated at 0, 2.5, 5.0, or 7.5 kGy. Samples were analyzed for lipid oxidation, volatile production and odor characteristics. Refrigerated samples were analyzed at 0, 1 and 2 weeks, and frozen ones after 0, 1.5 and 3 months of storage. With vacuum packaging, the lipid oxidation (TBARS) of both refrigerated and frozen patties was not influenced by irradiation and storage time except for the patties irradiated and refrigerated at 7.5 kGy. With refrigerated storage, panelists could detect irradiation odor at day 0, but not after 1 week at 4 degrees C. With frozen storage, however, irradiation odor was detected even after 3 months of storage. With aerobic packaging, the TBARS of refrigerated pork patties increased with storage time. The TBARS of pork patties increased as irradiation dose increased at day 0, but the effect disappeared after 1 week at 4 degrees C. Nonirradiated patties were preferred to the irradiated ones at day 0 because of the significant irradiation odor in the irradiated ones, but the off-odor disappeared after 1 week at 4 degrees C. With frozen storage, patties irradiated at 7.5 kGy had higher TBARS than those irradiated at lower doses. Nonirradiated patties had higher preference scores than the irradiated ones for 1.5 months in frozen storage. Sulfur-containing compounds were responsible for most of the irradiation off-odor, but these volatilized quickly during storage under aerobic conditions. Overall, vacuum packaging was better than aerobic packaging for irradiation and subsequent storage of meat because it minimized oxidative changes in patties and produced minimal amounts of volatile compounds that might be responsible for irradiation off-odor during storage. PMID- 22061911 TI - Distribution of alpha-tocopherol in beef muscles following dietary alpha tocopheryl acetate supplementation. AB - The objective of this study was to determine the effect of dietary vitamin E supplementation on the distribution and concentration of alpha-tocopherol in beef muscles. Crossbred cattle (n=8) were selected and divided into two groups and fed diets containing 20 (basal) and 3000 mg (supplemented) alpha-tocopheryl acetate/head/day for 135 days prior to slaughter. Carcasses were split centrally and chilled at 4 degrees C for 10 days. Muscles (n=16) were identified and removed from the left side of each animal and stored at -20 degrees C until required. Mean alpha-tocopherol levels in muscles were significantly (P<0.05) higher in all supplemented muscles with the exception of m. infraspinatis and m. deltoidous compared to controls. Mean alpha-tocopherol levels in muscles from the supplemented group decreased in the order m. supraspinatis > m. psoas major > m. trapezius > m. gluteus medius > m. triceps caput brachii lumborum > m. rhomboidous > m. seratus ventralis > m. gluteobiceps > m. semitendinosus > m. semimembranosus > m. infraspinatis > m. subscapularis > m. tricepscaputbrachiilaterale > m. deltoidous > m. longissimus thorasis > m. longissimus lumborum. Significant (P<0.05) differences in alpha-tocopherol distribution within muscles were observed for supplemented m. psoas major and control m. seratus ventralis (highest levels in posterior ends and lowest in anterior ends) only. However, trends showed definite distribution patterns for other muscles. Levels of alpha-tocopherol were found to be highest in oxidative muscles (m. psoas major and m. gluteus medius) and lowest in glycolytic muscles (m. longissimus thoracis and m. longissimus lumborum) while moderate levels of alpha-tocopherol occurred in intermediate muscles (m. semimembranosus). PMID- 22061912 TI - Combined effects of NaCl and raw meat pH on water-holding in cooked sausage with and without added phosphate. AB - The intake of sodium in diets is of concern in many industrialized countries. Attempts have been made to lower sodium intake via meat products. The keeping quality, taste and water-holding/firmness of meat products have usually been impaired. The water-holding in cooked sausage was determined by a laboratory sausage method. Beef and pork with varying natural post-rigor pH-values (range: pork 5.50-6.12 and beef 5.60-6.48) were used as mixtures, and 0.5-2.5 % NaCl was used with or without added commercial sausage phosphate (2,5 g/kg determined as P(2)O(5)). The pH-values of raw batter increased to a level 0.0-0.7 units higher than the pH-values of the respective meat mixtures. The increase was higher in lower pH-values, with higher salt levels and with added phosphate. The cooking caused an additional increase of about 0.0-0.2 units, and the increase was again higher at lower pH-values. Maximum in water-holding was reached in 2.5% NaCl in all pH-values, both with and without added phosphate. The pH-value of meat raw materials for the maximum water-holding was ca. 6.3. The combined effect of salt and pH is important in high salt contents and low pH-values. By 2.5% NaCl , where the maximum in water-holding was obtained, raw meat pH has the largest effect, but in low NaCl contents, below 1.0%, only a minor effect in pH-values below 5.9, and above that, almost no effect. Approximately the same water-holding as with 2.5% NaCl in pH 5.7 can be reached with 1.5% NaCl in pH 6.1 and above. The effects of the variables were similar with pork and beef. It was concluded that when lowering the salt content in cooked sausages, the pH of the batter should be increased by using high-pH meat mixtures and/or pH-raising phosphates in order to reach a high enough level of water-holding. PMID- 22061913 TI - Primal joints and hind-leg cuts of entire and castrated Javan rusa (Cervus timorensis russa) stags. AB - The effects of castration on the primal joints and the cuts of the leg joint of Javan rusa (Cervus timorensis russa) stag carcases was investigated at three slaughter ages (13, 19 and 25 months). Castration reduced the weights of some primal joints in the 19- and 25-months age groups, but not at 13 months. At 19 months, the neck, and neck plus chuck, were heavier by 35 and 17% respectively in entires (P<0.05), and at 25 months entires had heavier carcases, shoulder, forequarter and hindquarter (P<0.05). The leg and saddle joints were approximately 39 and 18% of the side, respectively, for both treatments and all ages. The proportions of the neck, and neck plus chuck, were higher (P<0.05) in 19-month old entires than castrates. There were few significant differences between treatments in the weight or proportion of the hind leg cuts at any slaughter age, but in the 25-months group the silverside was 8% (P<0.05) heavier in entires. In both castrates and entires, there appeared to be an increase in the percentage of the rump as the animals grew from 13 to 19 months of age. PMID- 22061914 TI - The effect of ageing on the water-holding capacity of pork: role of cytoskeletal proteins. AB - The water-holding capacity (WHC) of pork decreases post-mortem but has been shown to increase during subsequent ageing. In order to test a hypothesis that water holding capacity increases during ageing due to degradation of the cytoskeleton, WHC was followed 10 days post-mortem and related to the extent of proteolysis of cytoskeletal proteins. A fast method for measuring WHC in small meat samples was developed by the use of centrifugation. The WHC of fresh pork decreases in the first part of post-mortem storage after which it increases to the level of 1 day PM. No changes in total water content of the meat were observed which could explain changes in WHC during ageing. Vinculin and desmin degrade gradually during ageing while talin degrades rapidly. These observations are consistent with the hypothesis that degradation of the cytoskeleton slowly removes the linkage between lateral shrinkage of myofibrils and shrinkage of entire muscle fibres, so removing the force that causes flow into the extracellular space. Inflow of previously expelled water is then possible, so increasing WHC as observed in later periods of storage. PMID- 22061915 TI - Differentiation of dietary regimene of Iberian swine by means of isotopic analysis of carbon and sulphur in hepatic tissue. AB - The aim of this work was to differentiate the feed received by Iberian swine during fattening (acorns, feed) and their breed (Iberian or White) using analysis of the stable isotopes of carbon (delta(13)C) and sulphur (delta(34)S) in liver tissue samples. The results obtained in the determination of delta(34)S, using a procedure in which organic and inorganic sulphur are converted into BaSO(4) and the procedure that measures delta(34)S in samples of dried ground liver tissue were compared. Joint analysis of carbon (delta(13)C) and sulphur (delta(34)S) permits the differentiation of swine of different breeds receiving different diets (acorns or feed). PMID- 22061916 TI - Detection of mechanically recovered chicken meat using capillary gel electrophoresis. AB - This study investigated the use of capillary gel electrophoresis (CGE) as a method for differentiating between raw mechanically recovered chicken meat (MRM) and hand deboned chicken breast meat (HDM). Twenty samples of MRM were obtained and twenty samples of HDM were prepared in the laboratory. They were extracted and analysed using ProsortTM SDS-protein analysis reagent. There were obvious differences in the relative peak areas within the profiles obtained which distinguished raw MRM from raw HDM; specifically, that of haemoglobin was higher in MRM. Using the peak area of haemoglobin and its ratio to other peaks, the technique was tested using composite MRM-HDM mixtures. The results suggest that it is possible to differentiate mixtures containing 7.5% MRM from that of 0% MRM using the CGE method. PMID- 22061917 TI - Application of an exponential model to early postmortem bovine muscle pH decline. AB - An exponential decay equation was used to describe the decline of pH in bovine M. longissimus thoracis et lumborum (LTL) muscle postmortem. Goodness of fit of the equation was tested by convergence of model criterion and contrasting predicted against expected pH values of LTL muscles from 24 Bos taurus steer carcasses measured 40, 60, 80, 120, 185 and 1440 min after stunning. The model was fitted to pH values measured, as well as to the measured pH values adjusted to arbitrary constant temperatures of 10, 20 or 30 degrees C. The model failed to converge for 46% of the muscles sampled in the data sets with measured pH. The model converged for 100% of the muscles with pH values adjusted to 10, 20 or 30 degrees C. Limits of agreement, heteroscedasticity and intraclass correlation analyses showed little difference in the fit of the model to pH values adjusted to either 10, 20 or 30 degrees C. Fitting this model to pH data adjusted to 20 degrees C will enable comparison of rates of pH decline between muscles of different temperatures postmortem or laboratory homogenates and facilitate relation of pH decline rate to aspects of beef quality. PMID- 22061918 TI - Evaluation of the antioxidant potential of natural food/plant extracts as compared with synthetic antioxidants and vitamin E in raw and cooked pork patties. AB - Antioxidant potential for previously identified optimum levels of aloe vera (AV), fenugreek (FGK), ginseng (G), mustard (M), rosemary (R), sage (S), soya protein (SPI), tea catechins (TC) and whey protein concentrate (WPC) were evaluated in raw and cooked patties manufactured from frozen pork. The optimum levels determined were: AV (0.25%), FGK (0.01%), G (0.25%), M (0.10%), R (0.10%), S (0.05%), SPI (0.10%), TC (0.25%) and WPC (4%). Test ingredients were evaluated against synthetic antioxidants butylated hydroxyanisole/butylated hydroxytoluene (BHA/BHT) (0.01%) and a supplemented meat containing natural antioxidant, alpha tocopherol (1000 mg alpha-tocopheryl acetate/kg feed). Ranking the decreasing antioxidant effectiveness of added ingredients in raw patties on day 9 showed that: Control>G>SPI>FGK>AV>M>WPC>S>alpha-tocopherol>R>TC>BHA/BHT. Cooking resulted in a four-fold increase in TBARS values over raw patties with TC being the most effective antioxidant having significantly (P<0.001) lower TBARS values than the cooked control on days 3, 6 and 9. Ranking of decreasing antioxidant effectiveness of added ingredients showed that: M>SPI>G>FGK>alpha tocopherol>AV>control>S>BHA/BHT>R>WPC>TC. BHA/BHT had the most beneficial effect on cooked meat redness with Hunter 'a' values being significantly (P<0.05) higher than the control on days 3, 6 and 9. Ranking of Hunter 'a' values for added test ingredients showed that FGK>WPC>control>R>BHA/BHT>alpha tocopherol>TC>AV>SPI>M>G>S on day 9. Hunter 'L' and 'b' values showed no significant trend over the storage period in either raw or cooked patties. The pH values of both raw and cooked pork control patties and products containing added test antioxidants were variable and while a number of trends were observed, no significant differences were recorded between samples. PMID- 22061919 TI - Assessment of cooked alpaca and llama meats from the statistical analysis of data collected using an 'electronic nose'. AB - As part of an EU-funded project to assist in developing the production chain of meat from camelids in South America we have investigated the possibility of using an electronic nose to distinguish between the different types of meat of commercial interest. On-site monitoring of freshly cooked camelid meat using a Bloodhound electronic nose has been carried out in Peru and Bolivia. Sampling was carried out using inert, collapsible plastic bags. Linear discriminant analysis of data generated by the electronic nose classified the samples of meat. Some problems experienced in analysing the data relating to sample size are discussed. PMID- 22061920 TI - A novel polymerase chain reaction (PCR) - denaturing gradient gel electrophoresis (DGGE) for the identification of Micrococcaceae strains involved in meat fermentations. Its application to naturally fermented Italian sausages. AB - A new molecular method consisting of polymerase chain reaction (PCR) amplification and denaturing gradient gel electrophoresis (DGGE) of a small fragment from the 16S rRNA gene identified the Micrococcaceae strains isolated from natural fermented Italian sausages. Lactic acid bacteria, total aerobic mesophilic flora, Enterobacteriaceae and faecal enterococci were also monitored. Micrococcaceaea control strains from international collections were used to optimise the method and 90 strains, isolated from fermented sausages, were identified by biochemical tests and PCR-DGGE. No differences were observed between the methods used. The results reported in this paper prove that Staphylococcus xylosus is the main bacterium involved in fermented sausage production, representing, from the tenth day of ripening, the only Micrococcaceaea species isolated. PMID- 22061921 TI - Effect of air relative humidity on ham rind and subcutaneous salted fat during the resting period. AB - This study evaluated the effect of different air relative humidities (RH) on the nature and structure of the rind of dry-cured ham and of salted subcutaneous fat. After salting 16 hams were stored for 40 days at 4 degrees C, and at two different RHs (50-55 and 80-85%). Salted subcutaneous fat samples were stored for 30 days at 15 degrees C and at different RH (57.7, 70.8, 75.3 and 80.0%). Storage of hams at 50-55% RH after salting produced a whiteness on some parts of the rind, due to precipitation of salt inside the rind. Fat samples stored at 80.0% RH showed no oil drip and the fat cells observed microscopically were similar to non-salted cells. In contrast, fat samples stored at 57.7 and 70.8% RH showed oil drip and the fat cells from the external layer showed a wrinkled aspect in the optical microscope. Samples stored at 75.3% RH showed only a slight oil drip at the edges. PMID- 22061922 TI - Beef colour evolution as a function of ultimate pH. AB - Colour in CIELAB space was assessed in 31 yearling entire male cattle from their reflectance spectra (400-700 nm) at six different times (0 min, 15 min, 5 h, 48 h, 6 days and 9 days). Cluster analysis applied to all the colour co-ordinates divided the samples into two groups according to their ultimate pH (pHu): pH<6.1 and pH?6.1. pH ranged between 5.17 and 7.10. Colour development in pH?6.1 group was less visually appreciable than in pH<6.1 group. This difference was also observed in the reflectance spectra. The application of discriminant analysis to these groups established that b* and h* CIELAB co-ordinates are the most discriminant variables. Meat pigment evolution was assessed by the spectrophotometric indexes. R (infinity)(632)- R (infinity)(614); K S (614)- K S (632) and the K S (630)- K S (580) indexes were found to be the most significant to represent the difference between the two groups. PMID- 22061923 TI - Factors affecting the pH decline in lamb after slaughter. AB - Early postmortem pH has been linked to meat tenderness, especially in electrical stimulation and/or rapid chilling applications. In order to evaluate factors that affect pH, a trial was carried out in which 96 lambs were slaughtered over a period of 12 months. Carcass traits including age, sex and weight were recorded and the pH of M. longissimus thoracis et lumborum was measured at 0.5, 1.5, 4 and 24 h postmortem. Significant differences in pH were present over the 12 months but these differences could not be attributed to seasonal or age factors. The sex of the animal had no effect on early pH (0.5 h, 1.5 h) or final pH (24 h), but the 4 h pH of female lambs was lower than that of male lambs (P<0.001). Regression analysis, using 0.5 h pH and other measured traits, showed that individual male and female prediction models were better (R(2)=0.80 and RSD=0.10) for predicting 4 h pH than a combined model (R(2)=0.74 and RSD=0.11). PMID- 22061924 TI - Subcutaneous and intermuscular fat characterisation of dry-cured Iberian hams. AB - The fatty acid composition of the triacylglycerols and free fatty acids of subcutaneous (internal and superficial layers) and intermuscular fat and the contribution of these fatty acids to the formation of volatile compounds were determined in dry-cured Iberian ham. The profile of the fatty acids and volatile compounds showed that lipolytic and oxidative processes occur more intensively in subcutaneous than intermuscular fat, however, few differences were found compared to those found in ham lean. PMID- 22061925 TI - Volatile compounds released during ripening in Italian dried sausage. AB - A commercial production was analysed at six stages during ripening. Water content, pH and bacterial counts were followed, and volatile compounds from sausages were extracted by dynamic headspace sampling and analysed by gas chromatography/mass spectrometry. Total concentrations of all classes increased during ripening. Pepper compound concentrations peaked in the middle of the ripening period. Lipid oxidation products increased especially towards the end of ripening, in particular, the compounds 2-heptanol, 1-octen-3-ol, 2-heptanone and 2-nonanone. Surface moulds probably caused 4-heptanone to appear late in the processing. Benzeneacetaldehyde was absent in fresh mince, but increased to become one of the most abundant volatiles. Compounds from carbohydrate catabolism disappeared during the processing. PMID- 22061926 TI - Physicochemical and sensory properties of Galician chorizo sausage preserved by refrigeration, freezing, oil-immersion, or vacuum-packing. AB - Galician chorizo sausage is a traditional cured meat product from northwest Spain. We monitored changes in the physicochemical and sensory properties of Galician chorizo sausage conserved by four different methods, namely refrigeration, freezing, immersion in sunflower oil, and vacuum-packing. Refrigeration was the least effective method tested, with rapid deterioration of sensory properties, and oxidative spoilage evident from week 4 onward. Oil immersion and vacuum-packing gave reasonable conservation of sensory properties (despite some masking of aromas by the oil). Freezing gave acceptable conservation of sensory properties, and by week 6 there was still no evidence of oxidative spoilage. PMID- 22061927 TI - Genetic traceability of livestock products: A review. AB - Traceability is the ability to maintain the identification of animal, or animal products, all along the production chain. It represents an essential tool to safeguard public and animal health and to valorize typical production systems. European food legislation is particularly strict and traceability systems, based on product labeling, have become mandatory in all European countries. However, the implementation of this system does not ensure consumers against fraud. Paper documents can be counterfeit so researchers have focused on the study of genetic traceability systems based on products identification through DNA analysis. In fact DNA is inalterable, detectable in every cell, resistant to heat treatments, and allows for individual, breed or species identification. Even if results are promising, these techniques are too expensive to be converted in routine tests but they could be a trusted tool for verification of suspected fraud. The present review proposes a synthesis of the major advances made in individual, breed, and species genetic identification in the last years, focusing on advantages and disadvantages and on their real future applications for animal productions. PMID- 22061928 TI - Effects of vitamin A supplementation on growth performance, carcass characteristics and meat quality in Limosin*Luxi crossbreed steers fed a wheat straw-based diet. AB - Three experiments were conducted to examine the effects of dietary vitamin A supplementation on performance and carcass parameters in Limosin*Luxi crossbreed finishing steers fed a wheat straw-based diet. Sixteen 12-month old (301+/-22kg) steers, 16 12-month old (309+/-15kg) steers and 16 24-month old (411+/-20kg) steers were used in experiment 1 for 6 months feeding period, in experiment 2 for three months feeding period and in experiment 3 for three months feeding period, respectively. Sixteen steers of each experiment were randomly divided into the four groups of four animals. Treatments consisted of four vitamin A supplementation levels (0, 1100, 2200 and 4400IU/kg DM). The growth rate was affected by dietary vitamin A level in experiment 1 and 2, revealing that the suitable amount of vitamin A supplementation increased the growth rate; excessive vitamin A in the ration decreased the growth rate of 12-month-old finishing steers. The marbling deposition decreased with the increment of vitamin A supplementation level, but possibly associated with vitamin A supplementing duration. Furthermore, the suitable dietary vitamin A level probably decreased lipid and pigment oxidation, and increased the tenderness of beef meat. Vitamin A supplementation had no significant effect on chemical composition of gluteus medius muscle and longissimus dorsi muscle. PMID- 22061929 TI - Muscle and meat quality characteristics of Holstein and Salers cull cows. AB - Muscle characteristics and sensory rating of meat were determined in M. longissimus thoracis (LT), M. semimembranosus (SM), M. semitendinosus (ST) and M. triceps brachii (TB) from seven Holstein (HO, dairy breed) and six Salers (SA, beef breed) cull cows slaughtered at 6-7 years of age at the same fat score. Significant differences (P<0.001) among muscle types were observed: ST was the more glycolytic and TB the more oxidative; total collagen: ST>SM=TB>LT; initial and overall tenderness: LT>TB=SM>ST, juiciness: TB>LT=SM>ST. Flavour differed only between breeds: HO>SA (P<0.01). Three tenderness classes (high, intermediate, low) were determined from scores for sensory overall tenderness for all 52 meats: the lower total and insoluble collagen contents, the more oxidative metabolism, the more tender was the meat. Muscle type, and not breed explained most of the variability of meat quality from dairy and beef cull cows slaughtered at the same age and fat score. PMID- 22061930 TI - The production and microbiological status of skin-on sheep carcasses. AB - There is a demand by certain ethnic consumer groups in the United Kingdom for skin-on, singed carcasses, primarily from older sheep, but their production is illegal under current EU legislation. The aim of this study was to devise a protocol to produce carcasses having the desired 'smoked' colour and odour and an acceptable microbiology. A successful result could form the basis of a case to revise the legislation. Three key steps in the selected procedure were carcass singeing using specially designed gas burner equipment, pressure washing to clean the carcass and then evisceration. It was shown that a second heat application, termed 'toasting', if applied after evisceration, significantly (P<0.001) reduced Enterobacteriaceae and TVC counts on carcasses before chilling. Microbiological quality was also improved when toasting was the final step, following carcass splitting and inspection. Carcasses produced in this way had significantly (P<0.001) lower Enterobacteriaceae and TVC counts before chilling than conventionally dressed sheep carcasses produced in the same abattoir. PMID- 22061931 TI - Changes in carcass composition and meat quality when selecting rabbits for growth rate. AB - Sixty rabbits from the 23rd generation (group S) of a line selected for growth rate were compared to sixty rabbits from the 7th generation of the same line (group C) to study possible relevant changes in carcass composition and meat quality due to the selection and the consequent decrease in degree of maturity at slaughter weight (2000g). The only relevant changes in carcass composition were an increase in kidneys, liver and dissectible fat percentages and a decrease in meat to bone ratio of the hind leg. In m. Longissimus, group S had lower yellowness of the carcass and higher redness and yellowness of the meat. ICDH activity increased and the aldolase:ICDH ratio decreased. In the hind leg, group S had higher values of PUFA, PUFA/SFA ratio and n-3 fatty acids. PMID- 22061932 TI - Effect of fiber type on postmortem proteolysis in longissimus muscle of Landrace and Korean native black pigs. AB - The current study was conducted to characterize objective meat quality, fiber type and their relations to postmortem proteolysis in longissimus muscle of Landrace and Korean native black (KNP) pigs. Longissimus muscles from each 10 market-weighted male pigs were removed after conventional slaughtering and chilling procedures, and aged for 1 or 7 days at 4 degrees C to determine WB shear force, objective meat color, proportion of myosin heavy chain I (MyHC I), intramuscular fat content and rate of proteolysis by a proteomics approach. KNP had a significantly (p<0.05) higher content of MyHC I, and that concurred with greatly (p<0.05) higher intramuscular fat content and Hunter a(*) value, and significantly (p<0.05) lower drip loss than those seen in Landrace. One-dimension SDS-PAGE indicated that GAPDH, troponin I and creatine kinase were prominent proteolytic products during chiller ageing. By applying a gel-based proteome analysis, 26 proteins were identified, which showed different degradation properties during ageing between the breeds. Biopsied sample revealed that myosin regulatory light chain 2, myosin light chain isotype v/sb, fatty acid-binding protein and albumin were expressed at a greatly higher level for KNP, but their relation to fiber type (or genetic background) is unclear. It was particular noticeable that different actin isoforms showed various degradation behavior during ageing time. PMID- 22061933 TI - Calcium chloride and tricalcium phosphate effects on the pink color defect in cooked ground and intact turkey breast. AB - Calcium chloride (250, 500ppm) was examined for its ability to reduce the pink color defect induced by sodium nitrite (10ppm) and nicotinamide (1.0%) in cooked ground turkey in the presence and absence of sodium tripolyphosphate (0.25, 0.5%) and sodium citrate (0.5, 1.0%). The ability of tricalcium phosphate (0.1-0.5%) to reduce pink cooked color also was evaluated in ground turkey and both calcium chloride and tricalcium phosphate were tested for their effects on pink cooked color in whole breast muscle. The combination of calcium chloride and sodium tripolyphosphate, not calcium chloride alone, was necessary for a reduction in pink cooked color induced by nicotinamide. Subsequently, in the presence of phosphate, both calcium chloride and sodium citrate reduced pink cooked color and were most effective in combination. Tricalcium phosphate also was capable of reducing pink cooked color in ground turkey, however substituting tricalcium phosphate for sodium tripolyphosphate resulted in lower pH and cooking yields. Neither calcium chloride nor tricalcium phosphate was capable of reducing pink cooked color in whole turkey breast. Currently, a combination of sodium tripolyphosphate, calcium chloride, and sodium citrate represents the most suitable means for reducing or preventing the pink color defect in uncured ground turkey. PMID- 22061934 TI - Depth of concussion in cattle shot by penetrating captive bolt. AB - The prevalence of shallow depth of concussion following captive bolt shooting was assessed in 1608 cattle at an abattoir. Depth of concussion was determined in each animal from physical collapse, presence or absence of corneal reflex, normal rhythmic breathing, eyeball rotation, and whether the animal was re-shot. The presence of nystagmus and the absence of tongue protrusion were also monitored as potential indicators of a shallow depth of concussion, and simultaneous noise measurements assessed whether loudness of gun discharge was linked to concussion depth. The prevalence of a shallow depth of concussion was 8% for all cattle and 15% for young bulls. Nystagmus was associated with other indicators of a shallow depth of concussion. Absence of tongue protrusion was not associated with depth of concussion, but could serve as a useful indicator of jaw relaxation and insensibility following exsanguination. Soft-sounding shots (?111dB) when using 4.5 gr cartridges were associated with shallow depth of concussion. PMID- 22061935 TI - Suitability of three commercially produced pig breeds in Germany for a meat quality program with emphasis on drip loss and eating quality. AB - This study aimed at characterising 606 crossbred pigs of three commercially available breed types in terms of their carcass and meat quality. Breed G and H were German Large White (LW)*German Landrace (LR) sows sired with Pietrain (PI) boars, i.e. PI*(LW*LR). Breed S was 25% Duroc (DU), i.e. PI*(DU*LR). Most of the parameters were affected by breed and/or date of slaughter. The meat of crossbred pigs with 25% Duroc proportion appeared most favourable because of higher intramuscular fat content, lower drip loss and higher sensory liking scores. Conductivity is closely related to drip loss while the data suggests that the relationship is dependent on breed and carcass weight. The application of conductivity and lean meat yield thresholds to select carcasses with uniform and superior meat quality effectively decreased drip loss and increased intramuscular fat content as well as sensory liking scores. The variation of meat quality traits remains high, though. PMID- 22061936 TI - Dielectric behavior of beef meat in the 1-1500kHz range: Simulation with the Fricke/Cole-Cole model. AB - The electrical properties of biological tissues have been researched for many years. Impedance measurements observed with increasing frequencies are mainly attributed to changes in membrane conductivity and ion and charged-molecule mobility (mainly Na(+), K(+), CL(-) ions). Equivalent circuits with passive electrical components are frequently used as a support model for presentation and analyses of the behavior of tissues submitted to electrical fields. Fricke proposed an electrical model where the elements are resistive and capacitive. The model is composed of a resistive element (Rp) representing extracellular fluids (ECF) placed in parallel with a capacitive element (Cs) representing insulating membranes in series and a resistive element (Rs) representing intracellular fluids (ICF). This model is able to describe impedance measurements: at lower frequencies, most of the current flows around the cells without being able to penetrate them, while at higher frequencies the membranes lose their insulating properties and the current flows through both the extracellular and intracellular compartments. Since meat ageing induces structural change, particularly in membrane integrity, the insulating properties of membranes decrease, and intracellular and extracellular electrolytes mix, thus driving changes in their electrical properties. We report a method combining the Fricke and Cole-Cole models that was developed to monitor and explain tissues conductivity changes in preferential directions during beef meat ageing. PMID- 22061937 TI - Effect of carbon monoxide in modified atmosphere packaging, storage time and endpoint cooking temperature on the internal color of enhanced pork. AB - The objective of this research was to evaluate the effects of gas atmosphere, refrigerated storage time, and endpoint temperature on internal cooked color of injection-enhanced pork chops. Enhanced chops were packaged in 0.36% CO/20.34% CO(2) (CO-MAP), 80% O(2)/20% CO(2) (HO-MAP), or PVC-overwrapped (PVC-OW; controls), stored at 4 degrees C for 0, 12, 19 or 26 days, displayed for 2 days then cooked to six endpoint temperatures (54, 60, 63, 71, 77, and 82 degrees C). L(*), a(*), and b(*) values, hue angle and chroma were determined on the internal cut surface of cooked chops. Chops packaged in CO-MAP had the highest a(*) values; a(*) value began increasing on day 14. The lowest hue angles occurred in chops cooked to lower endpoint temperatures. Chops in CO-MAP had lower hue angles and higher chroma than those in HO-MAP and PVC-OW. Above 71 degrees C, hue angle and chroma increased. Overall, CO-MAP packaged chops stored for longer time periods then cooked to lower endpoint temperatures appeared reddest. HO-MAP packaged chops were less red, did not change over time, and appeared more well done at lower endpoint temperatures than those in other gas atmospheres. CO-MAP packaged chops retained redness even after cooking at 82 degrees C. PMID- 22061938 TI - Identifying constituents of whey protein concentrates that reduce the pink color defect in cooked ground turkey. AB - Whey protein concentrate constituents were tested for their ability to reduce naturally occurring pink color defect and pink cooked color induced by sodium nitrite (10ppm) and nicotinamide (1.0%) in ground turkey. beta-lactoglobulin (1.8%), alpha-lactalbumin (0.8%), bovine serum albumin (0.15-0.3%), lactose (1.0 3.0%), potassium chloride (500-1500ppm), and ferrous iron chloride (0.3-30ppm) had no effects on cooked pink color. Lactoferrin (30-5000ppm) increased or decreased pink color depending on its concentration in samples without added sodium nitrite or nicotinamide. Annatto (0.1-1.0ppm) reduced pink color whereas the higher concentration of magnesium chloride (22-88ppm) and ferric iron chloride (0.3-30ppm) increased pink color in samples with added nicotinamide. Calcium chloride (160-480ppm) was the only tested constituent that consistently reduced pink cooked color in samples with and without added nitrite and nicotinamide. Due to the variability of whey protein concentrates and the number of constituents that do not reduce pink cooked color, the addition of calcium alone or dried milk minerals containing calcium, phosphate, and citrate, represents a better means to regularly prevent the pink color defect in cooked ground turkey. PMID- 22061939 TI - Grape seed extract inhibits lipid oxidation in muscle from different species during refrigerated and frozen storage and oxidation catalyzed by peroxynitrite and iron/ascorbate in a pyrogallol red model system. AB - The antioxidant effect of grape seed extract (GSE) was determined by assessing the bleaching of pyrogallol red (PGR) by peroxynitrite or iron/ascorbate, and the formation of lipid hydroperoxides (LOOH) and thiobarbituric acid substances (TBARS) in raw or cooked ground muscle during refrigerated or frozen storage. In PGR models, GSE was more effective than gallic acid in inhibiting oxidation. The formation of LOOH and TBARS was inhibited by GSE (0.1% and 1.0%) compared to untreated controls and samples treated with sodium tripolyphosphate. Diethylenetriaminepentaacetic acid (DTPA), alone or in combination with GSE, had no effect on LOOH or TBARS, which provides clues about the possible mechanism of action of GSE. These results show that GSE at concentrations as low as 0.1% is a very effective inhibitor of primary and secondary oxidation products in various muscle systems and has potential as a natural antioxidant in raw and cooked meat systems. PMID- 22061940 TI - Effect of dietary oil source on the flavour and the colour and lipid stability of lamb meat. AB - This study investigated the influence of five sources of dietary oil (linseed oil (LO), fish oil (FO), a protected lipid supplement (PLS, 18:2 to 18:3 ratio 3:1), fish oil/marine algae (FOMA) and PLSMA) on the colour and lipid stability of lamb muscle and the flavour of grilled loin chops. LO produced the highest proportion of 18:3n-3 in muscle phospholipid, the highest ratings for lamb flavour intensity and overall liking and the lowest ratings for abnormal flavour intensity. PLS increased the proportion of 18:2n-6 which reduced lamb flavour intensity and increased abnormal lamb flavour intensity. Diets containing FO or MA increased proportions of the longer chain n-3 fatty acids and similar reduced ratings for lamb flavour as the PLS diet. FO-containing diets increased fishy flavour notes, especially when in combination with MA. 'Putty' and 'fish oil' odours were recognised as being present more frequently in cooked subcutaneous lamb fat from lambs fed FO and FOMA than other diets. Lambs fed MA, FO and the combination of the two produced meat that was oxidatively less stable and had a reduced colour and lipid oxidative shelf-life, which was at least partially due to the lower vitamin E content of the muscle. These results have significant implications for the formulation of diets that may improve nutritional ratios in lamb meat but which adversely affect flavour and meat stability. PMID- 22061941 TI - Screening of biogenic amine production by coagulase-negative staphylococci isolated during industrial Spanish dry-cured ham processes. AB - The potential to produce biogenic amines was investigated for 56 coagulase negative staphylococci isolated during industrial Spanish dry-cured ham processes. The presence of biogenic amines from bacterial cultures was determined by thin-layer chromatography. The percentage of strains that decarboxylated amino acids was very low (3.6%). The only staphylococci with aminogenic capacity were an histamine-producing Staphylococcus capitis strain, and a Staphylococcus lugdunensis strain that simultaneously produced putrescine and cadaverine. In both strains, PCR was used to confirm the presence of the genes encoding the amino acid decarboxylases responsible for the synthesis of these amines. This study reveals that production of biogenic amines is not a widely distributed property among the staphylococci isolated from Spanish dry-cured hams. PMID- 22061942 TI - Frozen storage stability of antioxidant-treated raw restructured beef steaks made from mature cows. AB - Previous research has shown that beef quality decreased with the age of cattle. In this study, beef trimmings from nine mature cows (n=9), equally representing three animal age groups (2-4, 6-8, and 10-12yr), were restructured into steaks formulated with propyl gallate, alone or in combination with a beefy flavoring agent, to enhance palatability and stability during 6months of frozen storage at 29 degrees C. Lipid oxidation, rancidity, and loss of beefy flavor in restructured steaks during extended storage were reduced by propyl gallate. The beefy flavoring agent inclusion masked mature, forage-fed beef off-flavors, intensified beefy flavor, and improved steak tenderness, juiciness and cooking yield. Thus, the combination of propyl gallate and beefy flavoring offers an effective means to enhance the palatability and storage stability of restructured beef prepared from mature cows. PMID- 22061943 TI - Traditional dry fermented sausages produced in small-scale processing units in Mediterranean countries and Slovakia. 1: Microbial ecosystems of processing environments. AB - Microbial ecosystems were surveyed in 314 environmental samples from 54 Southern and Eastern European small-scale processing units (PUs) manufacturing traditional dry fermented sausages. The residual microflora contaminating the surfaces and the equipment were analysed after cleaning and disinfection procedures. All the PU environments were colonised at various levels by spoilage and technological microflora with excessive contamination levels in some of the PUs. Sporadic contamination by pathogenic microflora was recorded. Salmonella and Listeria monocytogenes were detected in 4.8% and 6.7% of the samples, respectively, and Staphylococcus aureus was enumerated in 6.1% of the samples. Several critical points were identified, such as the machines for S. aureus and the tables and the knives for L. monocytogenes; this knowledge is crucial for the improvement of hygiene control systems in small and traditional meat processing industries. The variability of the residual contamination emphasized the different cleaning, disinfecting and manufacturing practices routinely followed by these small-scale processing units. PMID- 22061944 TI - Zn protoporphyrin IX is formed not from heme but from protoporphyrin IX. AB - We examined the effects of exogenous myoglobin, a bivalent chelator, and nitrite on Zn protoporphyrin IX (ZPP) formation by using model systems. ZPP was formed in a model solution without addition of exogenous myoglobin. After incubation, the amount of ZPP in a model solution was increased but that of heme was not decreased compared with the amounts before incubation. Protoporphyrin IX (PPIX) instead of ZPP also accumulated in a model solution with addition of EDTA, but the amount of heme was not reduced. These results suggested that ZPP was not formed by the Fe-Zn substitution in heme but was formed by the insertion of Zn into PPIX, which was formed independently. The fact that the effects of various factors in model systems with/without addition of a bivalent chelator were similar suggested that ZPP formation was strongly affected by PPIX formation. Inhibition of PPIX formation by nitrite might be the reason for the low levels of ZPP in cured meats. PMID- 22061945 TI - Temperature shows greater impact on bovine Longissimus dorsi muscle glycogen debranching enzyme activity than does salt concentration. AB - The degradation of glycogen progresses by the co-operation of two enzymes: glycogen phosphorylase (phosphorylase) and glycogen debranching enzyme (GDE). We studied the effect of temperature (4-42 degrees C) and salt concentration (0-3% NaCl) on bovine M. longissimus dorsi GDE activity. GDE activity (n=4) decreased significantly with decreasing temperature from about 40-4 degrees C. GDE exhibited 52% activity at 25 degrees C and 11% at 4 degrees C compared to its optimum activity measured at 39 degrees C. In rapidly chilled meat, the reduction in GDE activity may substantially delay the rate of glycolysis. However, residual GDE activity at 4 degrees C seems sufficient to enable the attainment of normal ultimate pH if the available time is long enough. An increase in salt concentration from 0% to 2% and to 3% induced a significant (P<0.001) increase in the ultimate pH of ground bovine meat (n=6), but showed no effect on GDE activity. PMID- 22061946 TI - Production of cured meat color in nitrite-free Harbin red sausage by Lactobacillus fermentum fermentation. AB - Lactobacillus fermentum was substituted for nitrite to produce cured pink color in a Chinese-style sausage. Treatments included inoculations (10(4), 10(6), and 10(8)CFU/g meat) followed by fermentation at 30 degrees C for 8h and then at 4 degrees C for 16h. Control sausage (with sodium nitrite, 60mg/kg meat) was cured at 4 degrees C for 24h without L. fermentum. The UV-Vis spectra of pigment extract from L. fermentum-treated sausage were identical to that of nitrosylmyoglobin (NO-Mb) formed in nitrite-treated control. The NO-Mb concentration and the colorimetric a(*) value of sausage treated with 10(8)CFU/g meat of L. fermentum essentially replicated those in nitrite-cured meat. Free amino acid content in sausage treated with L. fermentum was greater and the pH slightly lower compared with the nitrite-cured control sample. This study showed that L. fermentum has the potential to substitute for nitrite in the sausage production. PMID- 22061947 TI - Tenderness evaluation and mineral levels of llama (Lama glama) and alpaca (Lama pacos) meat. AB - Tenderness and mineral levels were determined in the Longissimus thoracis taken from 20 llama and 30 alpaca males reared in Peru and slaughtered at 25 months of age. Mineral contents were determined using an inductively coupled plasma emission spectrometer. Tenderness evaluation was determined two and seven days post slaughter using a Warner-Bratzler shear force device. Potassium is the mineral with the highest content, with a significant difference (P<0.05) between the two species of camelids. The other mineral contents were, in decreasing order, phosphorus, sodium, magnesium and calcium, in addition to smaller percentages of zinc and iron. Shear force values determined seven days post slaughter were significantly (P<0.01) lower in both the species compared with the results obtained two days post slaughter. PMID- 22061948 TI - A comparison in the composition of recovered meat produced from beef neckbones processed using hand boning, a traditional Advanced Meat Recovery (AMR) system, and a Desinewated Minced Meat system. AB - Beef neckbones were processed through a traditional Advanced Meat Recovery system (TAMR), a Desinewated Minced Meat machine with/without prior use of Jarvis saw for removal of spinal cord (DMMJ/DMMNJ), or hand boned with/without Jarvis saw (HJ/HNJ). This study investigated the composition of meat recovered by these five methods. Ranking from the most to least total fat percentage was TAMR (22.02%), HNJ (18.37%), HJ (14.69%), DMMNJ (11.14%), and DMMJ (9.76%); higher fat was related to less moisture. Protein was most for HJ (18.32%) and least for TAMR (15.79%). TAMR and HJ were similar (P>0.05) in ash content. Calcium was most in DMMJ (79.81mg); the least was found in the hand boned (HJ, 20.86mg/100g and HNJ, 23.66mg) lean. All samples contained calcium below the required limits set by USDA-FSIS. Total iron was the highest in TAMR (5.28mg of iron/100g), followed by DMMJ (3.65mg), DMMNJ (3.46mg), HJ (2.77mg), and HNJ (2.18mg). PMID- 22061949 TI - Chemical, instrumental and sensory characteristics of cooked pork ham. AB - Instrumental, chemical and sensory parameters of cooked pork ham were evaluated. Principal component analysis was carried out on the basis of the instrumental variables related to colour and texture. The four PCs account for almost 94% of the total variance in the data set. The PCA only separated 3 hams with a(*)>10. Hardness was correlated with non-collagen muscle protein (P?0.01), gumminess (P?0.01) and ash (P?0.05). Sensory evaluated tenderness showed positive significant correlation with L(*) (P?0.01). The most important colour parameter seems to be a(*), which was negatively correlated with sensory evaluated parameter colour (P?0.01). The PCA performed on all parameters (sensory, chemical and textural) discriminated two groups of hams differing in non-collagen muscle protein content and hardness. PMID- 22061950 TI - Conventional freezing plus high pressure-low temperature treatment: Physical properties, microbial quality and storage stability of beef meat. AB - Meat high-hydrostatic pressure treatment causes severe decolouration, preventing its commercialisation due to consumer rejection. Novel procedures involving product freezing plus low-temperature pressure processing are here investigated. Room temperature (20 degrees C) pressurisation (650MPa/10min) and air blast freezing (-30 degrees C) are compared to air blast freezing plus high pressure at subzero temperature (-35 degrees C) in terms of drip loss, expressible moisture, shear force, colour, microbial quality and storage stability of fresh and salt added beef samples (Longissimus dorsi muscle). The latter treatment induced solid water transitions among ice phases. Fresh beef high pressure treatment (650MPa/20 degrees C/10min) increased significantly expressible moisture while it decreased in pressurised (650MPa/-35 degrees C/10min) frozen beef. Salt addition reduced high pressure-induced water loss. Treatments studied did not change fresh or salt added samples shear force. Frozen beef pressurised at low temperature showed L, a and b values after thawing close to fresh samples. However, these samples in frozen state, presented chromatic parameters similar to unfrozen beef pressurised at room temperature. Apparently, freezing protects meat against pressure colour deterioration, fresh colour being recovered after thawing. High pressure processing (20 degrees C or -35 degrees C) was very effective reducing aerobic total (2-log(10) cycles) and lactic acid bacteria counts (2.4-log(10) cycles), in fresh and salt-added samples. Frozen+pressurised beef stored at -18 degrees C during 45 days recovered its original colour after thawing, similarly to just treated samples while their counts remain below detection limits during storage. PMID- 22061951 TI - Ascorbate, green tea and grape seed extracts increase the shelf life of low sulphite beef patties. AB - Green tea (GTE) and grape seed (GSE) extracts are proposed as preservatives for increasing the shelf life of low sulphite raw beef patties. The antioxidant and antimicrobial activities of both extracts were compared with ascorbate. Five groups were established for the patties: Control (with no additives), S (100 SO(2)), SA (100 SO(2)+400 sodium ascorbate), ST (100 SO(2)+300 GTE) and SG (100 SO(2)+300 GSE) (mg per kg of meat). Patties were stored at 4 degrees C in aerobic packaging for 0, 3, 6 or 9 days under retail display conditions. Meat spoilage (total viable and coliform counts, pH, lightness, chroma, hue angle, metmyoglobin and TBARS) was determined. The sensory contribution of the extracts to cooked patties was evaluated (colour, odour, flavour and texture). The results pointed to the possibility of using low SO(2)-vegetable extract combinations to preserve raw meat products. ST, SG and SA delayed microbial spoilage, redness loss and lipid oxidation, thus increasing the shelf life of the raw sulphite beef patties by 3 days. ST, SG and SA also delayed the onset of rancid flavours in cooked patties. No anomalous sensory traits were caused by either extract. Ascorbate, GTE and GSE improved the preservative effects of SO(2) on beef patties, especially against meat oxidation. This suggested that the quantity of SO(2) added can be reduced to obtain healthier raw meat products. PMID- 22061952 TI - Lipid and colour stability of beef from grazing heifers supplemented with sunflower oil alone or with fish oil. AB - The effect of sunflower and fish oil supplementation of grazing heifers on lipid oxidation and colour stability in beef was investigated. For 150 days, heifers were assigned unsupplemented grazing (G) or restricted grazing with 2.5kg concentrates containing 1250I.U. alpha-tocopheryl acetate and 290g sunflower oil (S1), 415g sunflower oil (S2), 290g sunflower+85g fish oil (FS1) or 415g sunflower+85g fish oil (FS2). Longissimus dorsi muscle was excised 24h post mortem and stored at -30 degrees C prior to analysis. Muscle alpha-tocopherol in the oil-supplemented groups was higher (P<0.05) than the G group. Lipid oxidation in refrigerated, minced raw or cooked beef was not significantly affected by diet but metmyoglobin was higher (P<0.05) in raw beef from oil-supplemented groups compared to the G group. Lipid oxidation and metmyoglobin formation increased (P<0.001) during refrigerated storage. Vitamin E supplementation together with pasture grazing appeared to offset any potential deleterious effect of oil supplementation on lipid and colour stability. PMID- 22061953 TI - Sorption isotherms of salted minced pork and of lean surface of dry-cured hams at the end of the resting period using KCl as substitute for NaCl. AB - The effect of KCl on sorption isotherms was determined on salted minced meat (with 0%, 30% and 100% molar substitution of NaCl by KCl) at 5 degrees C and 25 degrees C and meat from a 3mm thick slice from the surface of dry-cured hams (with 0% and 35% molar substitution of NaCl by KCl) held at 70-75%, 75-80% and 80 85% air relative humidity during the resting period. The sorption isotherms were determined gravimetrically by exposing the meat samples to several atmospheres of known relative humidity controlled by different saturated salts according to the COST90 method. The sorption equipment consisted of a chamber containing 11 containers, covering the water activity (a(w)) range from 0.112 to 0.946 at 25 degrees C. The hermetically closed sorption containers filled with KCl and minced meat samples were irradiated at 3kGrey (gamma irradiation (60)Co). The water content at equilibrium was higher in minced meat with NaCl than in minced meat with KCl (100% molar substitution of NaCl by KCl) at 5 degrees C within the range of 0.4313 and 0.7565 a(w). However, when substitution was 30% in minced meat and 35% in hams the isotherms were similar to isotherm without substitution. PMID- 22061954 TI - PCR assay for the identification of animal species in cooked sausages. AB - A species-specific PCR assay was developed for the detection of low levels of pork, horse and donkey meat in cooked sausages. Oligonucleotid primers were designed for amplification of species-specific mitochondrial DNA sequences of each species and detected the presence of 0.01ng of template DNA in water. When applying the assay to DNA extracts from sausages samples that were prepared from binary meat mixtures, it was possible to detect each species when spiked in any other species at the 0.1% level. In conclusion, it can be suggested that this assay can be used to determine mislabelled and/or fraudulent species substitution in comminuted meat products. PMID- 22061955 TI - Live weight and sex effects on carcass and meat quality of "Borrego terrincho PDO" suckling lambs. AB - Fifty seven suckling lambs (28 males and 29 females) of the Churra da Terra Quente breed were used to evaluate the effects of live weight and sex on carcass composition and meat quality traits. Lambs were slaughtered at three weight classes (<8kg, 8-11kg and >11kg) according to "Borrego Terrincho-PDO" specifications. The left sides of the carcasses were totally dissected. The longissimus thoracis and lumborum muscle was used for meat quality determination. Dressing proportion and carcass fatness were not affected by weight class or sex. Muscle proportion was similar in all carcass joints for the three weight classes. The percentage of bone decreased at the higher weight class, while that of subcutaneous and intermuscular fat increased. Female lambs had higher muscle proportions and greater muscle/bone ratios in the carcass side than males. Muscle pH, colour, cooking losses and tenderness were not affected by gender and weight class. Female lambs and weight classes 8-11kg and >11kg had higher proportions of intramuscular fat. PMID- 22061956 TI - Softness in dry-cured porcine biceps femoris muscles in relation to meat quality characteristics and processing conditions. AB - The aim of the study was to quantify the effect of meat quality characteristics and some processing conditions on the softness of dry-cured biceps femoris (BF) muscles. The BF muscles were dissected from forty hams and classified according to their pH(BF) into three groups: LpH (pH<5.66), MpH (5.66?pH?6.00) and HpH (pH>6.00). BF muscles within each pH(BF) group were distributed into three different Salting levels (1%, 2% or 4% of added NaCl). Muscles were salted, vacuum-packed and stored at 3 degrees C for 30 days. The post-salting BF muscles were classified into two intramuscular fat (IMF) levels: Low (IMF<4%) and High (IMF?4%). Thereafter, the muscles were divided into two pieces and dried at two of the three different Drying levels (1.5, 2 and 2.5g H(2)O/g desalted dry matter). Then, each piece was divided into two samples that were packed in N(2) and stored at 5 degrees C or 30 degrees C for 1 month. Stress Relaxation was used to evaluate texture. Dry-cured BF muscles with initial pH>6.0, with IMF>4% or with added NaCl levels less than 2% were more prone to show soft texture. Softness in dry-cured muscles can be reduced by applying an ageing temperature of 30 degrees C for 30 days, despite increasing proteolysis. The softness reduction by ageing at 30 degrees C compared with 5 degrees C is expected to be higher when applied to drier samples, which show a smaller increase in proteolysis. PMID- 22061957 TI - Humidification of unwrapped chilled meat on retail display using an ultrasonic fogging system. AB - The effects of an ultrasonic humidification system on unwrapped meat in a chilled retail display cabinet were assessed. Humidification raised the relative humidity of the cabinet air from a mean of 76.7% to just below saturation at 98.8%. This reduced the mean evaporative weight loss from whole samples of meat after 14h from 1.68% to 0.62% of their initial weight. The rate of deterioration in the appearance of the meat due to dehydration was reduced to the extent that while the unhumidified trial was terminated after 14h because all samples were judged to be unacceptable, the humidified trial was continued for 24h without any major changes in appearance. Levels of presumptive pseudomonas bacteria were relatively high in water samples taken from the humidification system and defrost water during the humidified trial, but Legionella spp. were not isolated. Significant increases in the numbers of bacteria on the meat during either trial were only found in one case, that of humidified minced beef. However, some of the samples had high counts even before display, and this may have masked any effect due to humidification. Differences in levels of air-borne contamination were small and inconsistent. Air temperatures were raised by humidification by between 1 and 2 degrees C and this was reflected in similarly raised product temperatures. Temperatures of air leaving the evaporator indicated that this was due to icing of the evaporator in the periods leading up to defrosts. PMID- 22061958 TI - Effect of level of linseed on fatty acid composition of muscles and adipose tissues of lambs with emphasis on trans fatty acids. AB - The effects of linseed content in concentrates on the fatty acid (FA) composition of adipose tissues and muscles of lambs were studied in a 2*4 design: males (M) vs. females (F) and linseed content (0%, L0, 3%, L3, 6%, L6, 9%, L9). FA proportions were determined both on a DB-wax and on a CP-Sil column in perirenal (PR), dorsal subcutaneous (SC) adipose tissue and in longissusmus dorsi muscle (IM). No effects of linseed contents in the diet on growth performances either in male or female lambs were observed. Linseed supplementation tended to decrease the fatness score. The proportion of linolenic acid increased linearly with the linseed content in the diet, from: 0.6, 0.5, and 0.5% for L0 to 1.9, 1.6, and 1.3% for L9, in PR, SC and IM, respectively. The increase in n-3 PUFA and in total PUFA was similar to that of linolenic acid. The n-6:n-3 ratio decreased from 5.7, 5.3 and 5.8 for L0 to 1.8, 1.7 and 2.7 for L9, in PR, SC and IM, respectively. There was no change in the proportion of docosahexaenoic acid with linseed supplementation. The proportions of C18:1trans-10 and C18:1trans-11 did not vary in PR, SC and IM with linseed supplementation. The total proportion of trans-octadecenoic acid was high in each tissue type and group of lambs. C18:1trans-10 represented about half of the total trans-octadecenoic isomers. With an increase in linolenic acid, most cis- and trans-octadecenoic isomers also increased, but trans-10 and trans-11 isomers did not and cis-9 and cis-11 isomers decreased. With linseed supplementation there was a decrease in the Delta9 desaturase indices in SC. PMID- 22061959 TI - Irradiation effect on fatty acid composition and conjugated linoleic acid isomers in frozen lamb meat. AB - The effect of gamma radiation processing on the lipid content, fatty acid composition and conjugated linoleic acid (CLA) profile in frozen lamb meat was investigated. Samples of longissimus thoracis muscle from lambs fed lucerne basal diets either unsupplemented or supplemented with polyunsaturated vegetable oils were irradiated (7kGy) and analysed. CLA contents in lamb meat did not affect (P>0.05) the levels of lipid oxidation induced by the irradiation. No significant differences (P>0.05) were observed for fatty acid composition, related nutritional indexes (n-6/n-3 and PUFA/SFA), as well as for total lipid and CLA contents, between non-irradiated (control) and irradiated meat samples. In contrast, meat irradiation affected the relative proportions of total trans,trans and cis/trans CLA isomers (P<0.001), in addition to the percentage of some minor individual CLA isomers (t11,t13 and t9,t11, with P<0.05 and P<0.001, respectively). The percentage of total cis/trans CLA isomers slightly decreased in irradiated samples, while the relative proportion of total trans,trans isomers slightly increased. This observation may be explained by the higher susceptibility to autoxidation of the cis double bond relative to the trans configuration. PMID- 22061960 TI - Effects of the inclusion of sodium bicarbonate and sugar beet pulp in the concentrate for fattening lambs on acid-base status and meat characteristics. AB - Thirty-six young Merino lambs (15.3kg live weight) were allocated into four equal groups to study the effects of the inclusion of sodium bicarbonate ('Bic', 0 vs. 2%) and sugar beet pulp ('SBP', 0 vs. 12%) in the concentrate on meat characteristics. Lambs were fed barley straw and concentrate ad libitum. When they reached 25kg a blood sample was taken and the animal slaughtered. After 24h meat characteristics (pH, colour, water holding capacity, Warner-Bratzler shear force, chemical and fatty acid - 'FA' - composition) were measured on M. longissimus thoracis et lumborum. SBP replacing 24% of the barley in the concentrate caused an increase in shear force (P<0.05) and saturated FA (P<0.05), decreasing meat unsaturated FA (P<0.05). SB increased blood base excess (P<0.05) and meat yellowness (P<0.05) and decreased meat pH (P<0.05), without altering any other meat characteristics. PMID- 22061961 TI - Evaluation of antioxidative properties of Geranium macrorrhizum and Potentilla fruticosa extracts in Dutch style fermented sausages. AB - Antioxidative properties of Geranium macrorrhizum, Potentilla fruticosa and Rosmarinus officinalis (as a reference) extracts were evaluated in Dutch style fermented sausages. Extracts were incorporated into sausages during preparation. The sausages were subsequently fermented, tested and compared to a standard spices mix, traditionally used for the production of such sausages. Formation of the primary oxidation products - peroxides, and secondary - TBARS and hexanal was monitored. The polar extracts from Potentilla showed some antioxidant activity, especially in combination with ascorbate, however the activity was low compared to the standard spices mix. Polar extracts from Geranium showed only negligible antioxidant activity. PMID- 22061962 TI - Ralston andrew lawrie (1924-2007): an appreciation. PMID- 22061963 TI - Human ether-a-go-go gene potassium channels are regulated by EGFR tyrosine kinase. AB - Human ether a-go-go gene potassium channels (hEAG1 or Kv10.1) are expressed in brain and various human cancers and play a role in neuronal excitement and tumor progression. However, the functional regulation of hEAG channels by signal transduction is not fully understood. The present study was therefore designed to investigate whether hEAG1 channels are regulated by protein tyrosine kinases (PTKs) in HEK 293 cells stably expressing hEAG1 gene using whole-cell patch voltage-clamp, immunoprecipitation, Western blot, and mutagenesis approaches. We found that the selective epidermal growth factor receptor (EGFR) kinase inhibitor AG556 (10 MUM), but not the platelet growth factor receptor (PDGFR) kinase inhibitor AG1295 (10 MUM) or the Src-family inhibitor PP2 (10 MUM), can inhibit hEAG1 current, and the inhibitory effect can be reversed by the protein tyrosine phosphatase (PTP) inhibitor orthovanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hEAG1 channels was reduced by AG556, and the reduction was significantly countered by orthovanadate. The hEAG1 mutants Y90A, Y344A and Y485A, but not Y376A and Y479A, exhibited reduced response to AG556. Interestingly, the inhibition effect of AG556 was lost in triple mutant hEAG1 channels at Y90, Y344, and Y485 with alanine. These results demonstrate for the first time that hEAG1 channel activity is regulated by EGFR kinase at the tyrosine residues Tyr90, Try344, and Try485. This effect is likely involved in regulating neuronal activity and/or tumor growth. PMID- 22061964 TI - PP2A phosphatase suppresses function of the mesenchymal invasion regulator NEDD9. AB - The mesenchymal mode of cancer cell invasion characterized by active adhesion turnover and a polarized actin cytoskeleton, is critically regulated by the adaptor protein NEDD9/HEF1/Cas-L. While it is known that NEDD9 is subject to extensive phosphorylation modification, the molecules that determine NEDD9 phosphorylation to stimulate adhesion turnover and mesenchymal cell morphologies are currently unknown. Earlier studies have suggested that the serine/threonine phosphatase PP2A regulates interconversion between a low molecular mass NEDD9 phosphoform and higher molecular mass phosphoforms. However, previous studies have used chemical inhibitors to block PP2A activity. In the present study we therefore aimed to specifically inhibit PP2A activity via siRNA and dominant negative approaches to investigate the effect of PP2A on interconversion between 115 kDa and 105 kDa NEDD9 and determine the functional consequence of PP2A activity for NEDD9 function. Strikingly, we find that while the phosphatase inhibitor Calyculin A indeed abrogates detachment-induced dephosphorylation of the 115 kDa NEDD9 phosphoform, PP2A depletion does not inhibit 115 kDa to 105 kDa interconversion. Our data suggest instead that PP2A targets discrete NEDD9 phosphorylation modifications separate to the events that mediate interconversion between the two forms. Functionally, PP2A depletion increases NEDD9 mediated cell spreading and mutation of S369 in the serine-rich region of NEDD9 to aspartate mimics this effect. Importantly, mutation of S369 to alanine abrogates the ability of dominant negative PP2A to increase NEDD9-mediated cell spreading. Collectively, our data reveal that the tumour suppressor PP2A may act via S369 to regulated NEDD9-mediated cell spreading. PMID- 22061965 TI - Cloacal exstrophy variant with intravesical phallus: further description of anatomy and implications for gender reassignment. AB - Variant presentations of cloacal exstrophy are exceedingly rare. Historically, genetic males with cloacal extrophy were re-assigned to the female gender due to phallic inadequacy. Early recognition of intravesical phallic structures in cloacal exstrophy cases may impact gender reassignment discussions and long-term gender outcomes. We report the case of a male infant with cloacal exstrophy presenting with an intravesical phallus, review and compare the presenting anatomical features of the three previously reported cases, and discuss the potential impact of these findings on gender reassignment in these complex children. PMID- 22061966 TI - A systems biology approach to nutritional immunology - focus on innate immunity. AB - Innate immunity and nutrient metabolism are complex biological systems that must work in concert to sustain and preserve life. The effector cells of the innate immune system rely on essential nutrients to generate energy, produce metabolic precursors for macromolecule biosynthesis and tune their responses to infectious agents. Thus disruptions to nutritional status have a substantial impact on immune competence and can result in increased susceptibility to infection in the case of nutrient deficiency, or chronic inflammation in the case of over nutrition. The traditional, reductionist methods used in the study of nutritional immunology are incapable of exploring the extremely complex interactions between nutrient metabolism and innate immunity. Here, we review a relatively new analytical approach, systems biology, and highlight how it can be applied to nutritional immunology to provide a comprehensive view of the mechanisms behind nutritional regulation of the innate immune system. PMID- 22061967 TI - MARK2/Par-1 guides the directionality of neuroblasts migrating to the olfactory bulb. AB - In rodents and most other mammals studied, neuronal precursors generated in the subventricular zone (SVZ) migrate to the adult olfactory bulb (OB) to differentiate into interneurons called granule and periglomerular cells. How the newborn cells navigate in the postnatal forebrain to reach precisely their target area is largely unknown. However, it is often thought that postnatal neurogenesis recapitulates the neuronal development occurring during embryogenesis. During brain development, intracellular kinases are key elements for controlling cell polarization as well as the coupling between polarization and cellular movement. We show here that the polarity kinase MARK2 maintains its expression in the postnatal SVZ-OB system. We therefore investigated the potential role of this kinase in adjusting postnatal neuroblast migration. We employed mouse brain slices maintained in culture, in combination with lentiviral vector injections designed to label neuronal precursors with GFP and to diminish the expression of MARK2. Time-lapse video microscopy was used to monitor neuroblast migration in the postnatal forebrain from SVZ precursors to cells populating the OB. We found that reduced MARK2 expression resulted in altered migratory patterns and stalled neuroblasts in the rostral migratory stream (RMS). In agreement with the observed migratory defects, we report a diminution of the proportion of cells reaching the OB layers. Our study reveals the involvement of MARK2 in the maintenance of the migratory direction in postnatally-generated neuroblasts and consequently on the control of the number of newly-generated neurons reaching and integrating the appropriate target circuits. PMID- 22061968 TI - Rac1b regulates NT3-stimulated Mek-Erk signaling, directing marrow-isolated adult multilineage inducible (MIAMI) cells toward an early neuronal phenotype. AB - Due to the limitations of neural stem cells to repair neuronal damage in the human brain, alternative approaches of repair using autologous adult stem cells have been examined for direct cell-replacement, or paracrine mediated neuroprotective effects. Human bone marrow-derived stromal cells (hMSCs) are a heterogeneous adult stem cell population with diverse immunomodulatory properties and the potential to differentiate into cells characteristic of all three germ layers. hMSCs are a renewable source of progenitor cells suitable for cell-based tissue repair. The marrow isolated adult multilineage inducible (MIAMI) cells developed by our laboratory are a developmentally immature homogeneous subpopulation of hMSCs that maintain self-renewal potential during ex vivo expansion, efficient differentiation capacity into neuron-like cells in vitro, as well as direct in vivo neuroprotection and functional recovery in animal models of neurological diseases. We now address the early signaling mechanisms regulating the neuron-like differentiation of MIAMI cells in vitro, in response to activation of the neurotrophic tyrosine-kinase receptor, type 3 (NTRK3) via neurotrophin 3 (NT3). We molecularly characterize a novel role for Rac1b mediating the neurogenic potential of MIAMI cells. Rac1b had an overall negative modulatory effect on the NT3-stimulated Mek1/2-Erk1/2 signaling pathway, proneuronal gene expression and neurite-like extensions. Rac1b was required for NT3-stimulated cell proliferation of MIAMI cells, yet was found to repress CCND1 and CCNB1 mRNA expression independent of NT3 stimulation, suggesting a dual neurotrophin dependent/independent function. Differential levels of Rac1b activity in hMSCs may explain the apparent contradictory reports regarding their neurogenic potential. These findings demonstrate the in vitro neurogenic potential of hMSCs as governed by Rac1b during NT3 stimulation. PMID- 22061969 TI - Quality of beef loin steaks as influenced by animal age, electrical stimulation and ageing. AB - The tenderness of beef M. longissimus dorsi muscles from cattle about 1 8 months (0-2 tooth) and 54 months (8 tooth) old at the time of slaughter was investigated. The influence of electrical stimulation on the mechanical and sensory panel assessments obtained for loin steaks was examined at 24 h post slaughter and also after ageing three weeks. Effective electrical stimulation of the carcasses produced, at 24 h from slaughter, steaks from both age groups which were uniform, acceptable and predictable in tenderness. The colour of loin steaks from the younger animals was lighter than loin steaks from older animals, while the weep in the vacuum packages was less for meat from the older animals than that from the younger ones. PMID- 22061970 TI - Gelation characteristics of muscle proteins from pale, soft, exudative (PSE) pork. AB - Thermally induced protein gels were made by using extracted salt-soluble proteins from normal pigs and stress-susceptible pigs determined to have pale, soft, exudative (PSE) muscle. Effects of heating rates (17,39 and 93 degrees C/h) at various protein concentrations (23, 34, 48 and 54 mg/ml) were evaluated. Gel strength of PSE extracts was 45% of the controls at equivalent protein concentration. Gel strength of normal and PSE-muscle protein gels from the first compression curve increased with increasing protein concentrations at all heating rates; however, gel strength was greater for slow heating rates than for fast heating rates in both PSE and normal samples. Percent water loss was greater for PSE extracts than for controls at the same protein concentration. Losses of 47% and 36% for PSE and controls, respectively, were observed at a a protein level of 54 mg/ml protein. There was no heating rate effect on water losses in either case. Protein loss was less, for both PSE and control, at low protein concentrations than at high protein content in the range studied. Slow heating rates resulted in less protein loss, for both PSE and control, whereas faster heating rates gave greater protein losses in the exuded water. PMID- 22061971 TI - Species differentiation of heated meat products by DNA hybridization. AB - A method for quantitation of pork in heat-treated meat products is described. The procedure involves isolation of DNA from meat samples followed by a determination of the average size of DNA fragments by agarose gel electrophoresis. The DNA is then immobilized on nylon membranes and hybridized with a (32)P-labelled probe made from genomic porcine DNA. The signal intensity from filter-bound DNA probe is determined by laser densitometry of the autoradiographs. Functional relationships between the signal intensity and the fragment size of the DNA as well as signal intensity and the amount of pork DNA have been established. Pork DNA can therefore be quantified using DNA standards with the same fragment size as the actual sample DNA. Samples of known composition and heat treatment have been investigated. The detection limit has been determined to approximately 0.1% pork in beef whereas for heat-treated samples the detection limit has been determined to approximately 0.5% pork in beef. Examples are given in which the present method has been applied on commercial canned and cold-stored foods. The results of the investigation indicate that the DNA-hybridization technique applying (32)P-labelled probes can be used for quantitative determinations in quality control of heat-treated meat products. PMID- 22061972 TI - Effect of light on colour and reaction of nitrite in sliced pork bologna under different chilled storage temperatures. AB - The effect of different lighting conditions (darkness and exposure to 1900 +/- 100 lux) on colour stability, conversion of added nitrite (residual nitrite, nitrite converted to nitrate, nitroso heme pigments, and protein-bound nitrite) and oxidative rancidity (2-thiobarbituric acid index) in sliced, vacuum-packaged pork bologna as a function of storage temperature (0 +/- 1 degrees C and 7 +/- 1 degrees C) was studied. Colour (redness) losses over the storage period were more dependent upon photochemical processes than on thermal processes, and the action of temperature on colour was attributable to its effect on microbial growth, which in turn also affects oxygen availability. Conversion of nitrite into the different fractions studied was chiefly temperature-dependent, but exposure to light lowered the residual nitrite content. Nevertheless, the effect of illumination on the constant rate of residual nitrite depletion was dependent on the storage temperature. Recovery of the added nitrite, i.e. the total of the nitrite in all the fractions combined, was highly dependent upon fluctuations in the residual nitrite levels and varied over the storage period. Under the conditions of the experiment, photo-oxidation did not appear to be a determining factor in lipid oxidation. PMID- 22061973 TI - Estimation of lamb carcass composition from measurements of the speed of ultrasound in the soft tissues of live animals and carcasses. AB - The application of the velocity of sound (VOS) technique to lamb carcasses in a previous study (Fisher & Page, 1986) measured composition at a hind limb and neck site but was not as precise as fat scores in predicting lean proportion. This study examines VOS measurements made at sites in the hind limbs and along the vertebral column in live sheep and carcasses. A group (A) comprising five breeds of males and females (n = 61) and a sub-group (B) of Scottish Blackface castrated males (n = 34) were studied, and the reciprocal velocity of ultrasound (RV) was measured on the live sheep immediately behind the shoulder and over the last rib using a fixed-distance transducer assembly operating at 5 MHz, and in the hind limbs at 2.25 MHz using the apparatus described by Miles et al. (1984). Corresponding measurements were made on the carcasses which were classified by a Meat and Livestock Commission fatstock officer and then dissected. Standard deviations of lean proportion were 4.48% (A) and 3.39% (B). The residual standard deviations (rsds) for groups A and B respectively were obtained using the following predictors: live mass (LM) 4.27% and 2.96%; LM + breed (B) 3.08% (group A only); LM + mean RV 2.36% and 2.07%; LM + B + mean RV 1.99% (group A only). Using carcass measurements: carcass mass (CM) 4.25% and 2.90%; CM + MLC fat score 2.99% and 2.12%; CM + RV last rib 2.89% and 2.02%. These data show that VOS measurements through dorsal sites of live sheep provide encouragingly precise estimates of carcass lean proportion. For carcasses, dorsal sites provide a less precise estimate of carcass lean but when carcass mass is included in multiple regression the precision of the correlation is comparable with that of multiple regression of fat score with carcass mass. PMID- 22061974 TI - A study on the possibilities of using 3-methylhistidine to quantify skeletal proteins in meat trimmings. AB - The aim of the study was to ascertain whether the amino acid 3-methylhistidine can be used to quantify skeletal meat protein in meat trimmings. 3-Methyhistidine from different carcass trimmings was quantified by a fluorescent HPLC method. Four trimmings with three subsamples each were examined. The subsamples were analysed in duplicate. The results showed high analytical variations between duplicates and subsamples. The average concentration of 3-methylhistidine in the four trimmings was 135 MUg/g fat-free and connective tissue-free meat. Compared to earlier studies this value is high. Because of the rather high analytical variation, further research must be done to evaluate the use of 3-methylhistidine as an indicator for skeletal meat proteins in whole carcass trimmings. PMID- 22061975 TI - Effect of recombinant porcine somatotropin on body composition and meat quality in growing pigs; Interactions with genotype, sex and slaughter weight. AB - Body composition in 96 pigs and meat quality in 36 pigs treated with porcine somatotropin (rpST) were investigated. Animals included both barrows and gilts from Pietrain, F(1) (Dutch Yorkshire * Dutch Landrace) and Duroc and were slaughtered at either 100 or 140 kg live weight. Treatment consisted of either 14 mg rpST or placebo twice weekly and started at 60 kg. Treatment with rpST enhanced the proportion of lean parts (on average +2.8% at 100 kg and + 5.5% at 140 kg) and reduced the proportion of fatty parts (-10.1% and -12.9% respectively). The latter tended to be more apparent in fatter animals (Duroc 14.5% and -13.3%, barrows -12.0% and -13.7%). Most organs increased in weight, especially kidneys (+14.8% at 100 kg and +17.6% at 140 kg). Meat quality parameters appeared to be not significantly affected, though intramuscular fat percentage was slightly decreased. Administration of rpST led to less fat and more uniformity in carcasses and meat quality among genotypes and sexes. No serious adverse effects were detected. PMID- 22061976 TI - Phosphates and antioxidants as cryoprotectants in meat batters. AB - The gelation and rheological properties of minced beef frozen and stored at -18 degrees C for 6 months without additives, with salt (1.5% NaCl), tripolyphosphate (TPP 0.5%), sodium acid pyrophosphate (SAPP 0.5%) and an antioxidant mix (BHA + BHT, 200 ppm) were studied. The relationships between shear rate and shear stress for the different treatments were nonlinear and resembled the Bingham pseudoplastic behaviour. Continuous evaluation of the modulus of rigidity (G) during cooking (0.5 degrees C/min) revealed higher G values for the unfrozen phosphate treatments. Salt addition resulted in significantly lower G values of the stored meat compared to the control. Antioxidant addition retarded some of these effects. Among the phosphates, TPP was the best in maintaining the same G values as the control. Water-holding capacity (after salt addition) was increased after phosphate addition in the unfrozen meat and did not change after storage. The control, NaCl and antioxidant treatments showed an increase in WHC during storage. PMID- 22061977 TI - Use of antioxidants to reduce lipid oxidation and off-odor volatiles of irradiated pork homogenates and patties. AB - Pork homogenates and patties treated with antioxidants (200 MUM, final) were irradiated with an electron beam. Lipid oxidation of the pork homogenates and patties were determined at day 0 and 5 and volatile compounds were analyzed soon after irradiation. Ionizing radiation accelerated lipid oxidation and produced S containing volatiles in pork homogenates and patties. Addition of an antioxidant (sesamol, gallate, Trolox, or alpha-tocopherol) and their combinations decreased, but carnosine did not affect the production of off-odor volatiles and lipid oxidation of pork homogenates and patties by irradiation. Antioxidant combinations showed distinct beneficial reduction in lipid oxidation of aerobically packaged irradiated pork patties. The effect of antioxidant combinations in reducing sulfur volatiles of irradiated pork patties was clearer under vacuum than aerobic conditions. PMID- 22061978 TI - Physical and sensory properties of low-salt phosphate-free frankfurters composed with various ingredients. AB - The physical properties and sensory attributes of phosphate-free frankfurters were examined using response surface methodology by varying the amounts of five compositional variables: salt, modified tapioca starch-, sodium citrate (NaC)- and wheat bran and fat in the batter. Altogether, 20 different types of frankfurters were prepared. When the frankfurters were made without phosphate, additional non-meat ingredients were needed at salt contents of less than 1.5%. Modified tapioca starch and sodium citrate decreased frying loss, with the former also improving water and fat binding. PMID- 22061979 TI - Pork quality variation is not explained by glycolytic enzyme capacity. AB - Our objective was to determine if increased glycolytic enzyme capacity accommodates rapid glycolysis, which leads to inferior pork color and water holding capacity. Progeny from HAL-1843 free Duroc (n=16) or Pietrain (n=16) sires were harvested over a 2-week period. Coupled enzyme assays were used to quantify total capacity of pyruvate kinase (PK) and phosphofructokinase (PFK) in the sarcoplasmic fractions and crude homogenates of longissimus muscle (LM), respectively. Capacity of PK was not correlated with LM pH (20, 45, 180 min or 24 h), purge, drip loss, or CIE L* (P > 0.2). However, PFK capacity was inversely related to fluid loss (P<0.05). This finding was unexpected, but may result from PFK becoming partially denatured and inactivated by 20 min postmortem in samples that undergo a rapid pH decline. These data indicate that lighter pork color and reduced water-holding capacity are not associated with an increase in the capacity of enzymes that catalyze regulated steps of glycolysis. PMID- 22061980 TI - Antioxidant and antimicrobial effects of four garlic-derived organosulfur compounds in ground beef. AB - The antioxidant and antimicrobial protection of diallyl sulfide (DAS), diallyl disulfide (DADS), s-ethyl cysteine (SEC), n-acetyl cysteine (NAC) in ground beef against discoloration, lipid oxidation and microbial contamination were studied. The exogenous addition of these garlic-derived organosulfur compounds significantly delayed both oxymyoglobin and lipid oxidations (P<0.05). The antioxidant protection from these organosulfur compounds was dose-dependent (P<0.05), and showed significantly greater antioxidant activity than alpha tocopherol (P<0.05). The presence of DAS and DADS in ground beef significantly reduced total aerobes and inhibited the growth of five inoculated pathogenic bacteria, Salmonella typhimurium, Escherichia coli O157:H7, Listeria monocytogenes, Staphyllococcus aureus and Campylobacter jejuni (P<0.05). These results suggested the application of these organosulfur compounds in meat or other food systems could enhance color, lipid and microbial safety. PMID- 22061981 TI - NaCl content and temperature effects on moisture diffusivity in the Gluteus medius muscle of pork ham. AB - Dry-cured meat products are salted with different amounts of NaCl and then dried under different conditions (temperature and relative humidity) in order to stabilize the product. The effective moisture diffusivity values (D(e)) in Gluteus medius muscles, unsalted or soaked in different salting solutions (0.02, 0.05 and 0.08 kg NaCl/kg H(2)O), and dried at different temperatures (5, 13, 19 and 26 degrees C) and 80% of air relative humidity were determined. Water diffusion was only allowed parallel to meat fibre direction. The D(e) values were determined by applying Fick's second law. As temperature increased or NaCl content decreased, the D(e) increased. At low temperatures, the D(e) was less dependent on NaCl content than at higher ones. The energy of activation, obtained from the Arrhenius equation, is lower for unsalted compared with salted samples. Therefore, the effective moisture diffusivity of salted meat products is more sensitive to temperature variations than that of unsalted meat. PMID- 22061982 TI - Effect of electrical stunning on meat and carcass quality in lambs. AB - The effect on meat quality and the presence of haemorrhages were assessed in head only electrically stunned and non-stunned lambs. Colour (L*, a*, b*), muscle ultimate pH (pHu), chilling losses and carcass weight at 45 min and 24 h were not significantly different between treatments. However, the amount of blood lost relative to live body weight and the killing-out were significantly higher (P<0.05) in electrically stunned lambs compared with non-stunned lambs. No carcasses with petechiae, ecchymosis, haematomas and bone fractures were found in either treatment. On the other hand, the incidence of hearts with petechiae was significantly (P<0.05) higher in electrically stunned lambs compared with lambs slaughtered without prior stunning. It is concluded that meat quality and the incidence of haemorrhages are unaffected by head-only electrical stunning for 3 s at a constant voltage of 250 V. PMID- 22061983 TI - Effect of dietary beta-carotene supplementation on beef color stability during display of two muscles from Japanese Black steers. AB - Effect of dietary beta-carotene supplementation (7500 mg/head/day) for 28 days prior to slaughter on beef color stability during display of M. semimembranosus (SM) and M. longissimus lumborum (LL) from Japanese Black steers was studied. Steak samples from two muscles were over-wrapped with PVC film and displayed under fluorescent lights at 4 degrees C for 12 days. Metmyoglobin percentages of steak samples were determined at days 0, 3, 6, 9 and 12. The beta-carotene concentration in both muscles was increased (P<0.001) by dietary beta-carotene supplementation. Color display-life of muscles was calculated by the metmyoglobin threshold method based on a threshold value of 20% metmyoglobin. Color display lives of SM and LL were extended 1.5 and 3 days by dietary beta-carotene supplementation, respectively. PMID- 22061984 TI - Oxidative stability of fermented goat meat sausage with different levels of natural antioxidant. AB - Goat meat was used for fermented sausage processing. The oxidative stability of the fermented goat meat sausage, containing two different levels of natural antioxidant (rosemary-Rosmarinus officinalis), at room temperature, was evaluated by way of periodical analyses for thiobarbituric reactive substances (TBARS), overall acceptance and descriptive sensory profile, for 90 days. The initial values for TBARS indicated that lipid oxidation occurred during the processing of the fermented sausages. Significant correlations were not found between the TBARS values and the sensory analysis, except for an oxidized aroma in the control sample and the overall acceptance after 75 days of storage. Formulations containing 0.05% rosemary showed the best characteristics in relation to oxidative stability, with the lowest initial values for TBARS, the greatest sum for the overall acceptance sensory, highest values for red color and lowest scores for oxidized aroma and flavor, when compared with the sample containing 0.025% rosemary. PMID- 22061985 TI - Effects of vitamin E supplementation on performance and meat quality traits of Morkaraman male lambs. AB - This research was carried out to determine the effects of vitamin E supplementation on meat quality traits of approximate 8 months of age Morkaraman male lambs. The lambs were divided into two groups-control (CG, n=7) and experimental (VG, n=6)-at the beginning of fattening period. The diet given to the CG and VG consisted of concentrate and grass hay. In addition, the VG received a supplement of 45 mg vitamin E per lamb in a day during a 75-day fattening period. At the end of the study, average daily weight gain and feed conversion efficiency values as to feed basis were found to be 208 g and 6.3 for CG and 223 g and 6.0 for VG groups, respectively. Vitamin E supplementation resulted in 8.8% improvement in feed conversion efficiency. In the same way, vitamin E supplementation resulted in 6.7% increase in daily weight gain. Slaughter and carcass characteristics of lambs were also determined, but fattening performance, slaughter and carcass characteristics were not significantly different between groups. The effects of vitamin E on meat characteristics, meat colour (L*, a* and b*), thiobarbituric acid reactive substances content (TBARS), drip loss and pH were determined using m. longissimus dorsi (LD) muscles obtained from CG and VG. Though the effect of vitamin E supplementation on most of the meat quality traits was not statistically significant (P>0.05), L* and a* values in LD muscle from VG were preserved for a period of 12 days of maturation. In addition, a* (redness) tended to increase slightly. TBARS values in samples from CG were found to be higher than those of vitamin E treatment group. In this study, it was also concluded that drip loss was relatively preserved by vitamin E supplementation. In conclusion, vitamin E supplementation of Morkaraman male lambs at an inclusion rate over the amount of nutritional recommendations, significantly reduced lipid oxidation, drip loss and tended to maintain meat redness. PMID- 22061986 TI - Identification and significance of the N-terminal part of swine pyruvate kinase in aged Parma hams. AB - Within a project aimed at studying the peptide fraction in dry-cured Parma hams, a peptide was purified by means of reversed phase-high performance liquid chromatography (RP-HPLC) and identified by its molecular mass and amino acid sequence analysis. The peptide showed a very high degree of homology with the N terminal part of different mammalian pyruvate kinases reported in databases and was accordingly identified as the N-terminal part of swine pyruvate kinase, whose sequence had never been reported before. The peptide was determined quantitatively by comparison with a suitable internal standard (Phe-Phe) in commercial ham samples with different age degrees. The peptide was found to be ubiquitous in Parma ham and its amount to increase during ageing even if a large variability was found within each assayed maturing time. The correlation found with the ham proteolysis degree (P<0.01) suggests that this peptide is related to the endopeptidasic activity. The peptide did not show a significant relationship with bitterness perception in assayed dry-cured ham, in agreement with the hypothesis that this taste is more related to free amino acids and low molecular weight peptides. PMID- 22061987 TI - Mobility of solutes in frozen pork studied by electron spin resonance spectroscopy evidence for two phase transition temperatures. AB - The mobility of solutes in frozen pork (longissimus dorsi) was studied by X band electron spin resonance spectroscopy (ESR) using the three water soluble spin probes TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), CAT 1 (4 trimethylammonium-2,2,6,6-tetramethylpiperidine-1-oxyl) and TEMPO choline (4-(N,N dimethyl-N-(2-hydroxyethyl))ammonium-2,2,6,6-tetramethylpiperidine-1-oxyl). The mobility was quantified as the observed hyperfine coupling constant A'(zz). The three spin probes, of which only the neutral TEMPOL may penetrate membranes, gave very similar values of A'(zz) as a function of the temperature. A'(zz) was constant at temperatures below -55 degrees C, whereas A'(zz) decreased as the temperature was increased above -55 degrees C. This behavior has been interpreted as an increase in the amplitude of the rotational oscillations of the spin probes (and other solutes) with temperature. Above -13 degrees C the spin probes gave isotropic ESR spectra indicating free rotational mobility in a molten liquid phase. These results are discussed in relation to glass transitions in frozen pork. PMID- 22061988 TI - Early postmortem electrical stimulation simulates PSE pork development. AB - Carcasses from 64 gilts were subjected to electrical stimulation (ES) at 3, 15, 25, 35, 45, and 55 min postmortem or were untreated (NS). Temperature and pH of longissimus muscles were recorded at 1, 7, 14, 20, 30, 40, 50, and 60 min, and 24 h postmortem. Muscle samples were collected at 1, 30 and 60 min, and 24 h for determining glycolytic metabolite concentrations. ES at 3, 15, and 25 min resulted in lower (P<0.05) muscle pH, but stimulation after 25 min had no effect on muscle pH. Likewise, ES prior to 25 min resulted in greater (P<0.05) muscle temperatures. Muscle lactate concentrations were greater (P<0.05) in carcasses stimulated before 45 min postmortem. Glucose 6-phosphate concentration decreased (P<0.05) during the first hr postmortem and increased (P<0.05) thereafter. ES of carcasses at 45 and 55 min resulted in higher (P<0.05) concentrations of muscle glucose 6-phosphate at 24 h compared with NS and early-stimulated carcasses. Muscle glycogen concentrations at 30 min in carcasses stimulated at 3, 15 and 25 min were lower (P<0.05) than NS carcasses. Carcasses stimulated at 3 and 15 min exhibited lower (P<0.05) concentrations of muscle glycogen at 60 min than NS carcasses. Carcasses stimulated at 3 and 15 min postmortem exhibited lower (P<0.05) color and firmness scores, while ES at 3 and 25 min postmortem resulted in lower (P<0.05) water holding capacity. ES had no significant effect on CIE L(*), a(*), b(*), or 24 h muscle pH. These data show that ES of pork carcasses during the first 25 min postmortem creates PSE-like quality characteristics and suggest that ES is a potential model for studying pork quality development. PMID- 22061989 TI - The potential impact of current animal research on the meat industry and consumer attitudes towards meat. AB - Progress in animal nutrition, reproduction, quantitative genetics, and the development of molecular genetics, proteomics, and functional genomics open new perspectives for the meat sector. The most promising developments include a wider utilisation of molecular markers, the possibilities of semen sexing and the targeted use of nutrition to modify the composition of meat. The increased use of biotechnology will have a considerable impact on the economics of production of meat and further processed products. New technologies will increase the possibilities for product differentiation and improve homogeneity of live animals. The consumer and society in general will influence the direction of these developments. This review will focus on the long-term impact of new technologies for the meat production chain. PMID- 22061990 TI - Chemical composition of pig meat from the genetic type 'Casertana' and its crossbreeds. AB - The meat quality of the autochthonous genetic type Casertana (Ca) and its crossbreeds was evaluated for the production of pork for fresh consumption and/or processing. The chemical composition of the fresh meat was determined on eight muscles of 143 pigs of six genetic types, of both sexes and slaughtered at three different live weights. The most important results of fixed analysis of variance showed that the first order interactions are statistically important in determining most of the analytical data considered; muscle is an important factor for ash content. On average, the dry matter percentage is higher in the Casertana; the opposite is observed in the Ca * [Landrace (L) * Large White (LW)]. The protein content, in relation to dry matter, is lower in the Casertana and higher in Ca * (L * LW) and L * (L * LW). The opposite results were observed for lipid contents and energy value. The ash content ranges from 4.8% in Ca to 5.3% in Ca * Duroc (Du). However, the above trends vary in relation to sex, live weight at slaughter and muscle. Females, compared with males, supply meat with high lipid contents and energy values. The protein content, by contrast, is higher in males. As the live weight at slaughter increases from 80-90 to 120-130 kg, the protein content rises, while the ash value decreases. In meat obtained from females no significant differences are observed in the analytical data from 80-90 to 120-130 kg, while in that from males the protein content increases, and the lipid content and energy value decrease. The Longissimus dorsi muscle (both at thoracic and lumbar level) has the highest content of dry matter, while the Supraspinatus and the Rectus femoris have the lowest. The Rectus femoris has the highest protein content and Semitendinosus the lowest. The opposite holds for lipid content and energy value; such results confirm the histochemical individuality of the muscle. The dry matter content of the 'bacon' cut is higher in the Casertana pigs and lower in L * (L * LW), which is due, in part, to the higher lipid content and lower protein content found in the former. PMID- 22061991 TI - Effect of dietary vitamin E supplementation on the shelf life of cured pork sausage. AB - This study examined the shelf life of cured sausage under different packaging conditions from vitamin E supplemented pigs. One group (n=6) of crossbred pigs received a normal fattening diet containing 20 ppm alpha-tocopherol for 39 days before slaughter. Another group was fed a diet containing 410 ppm alpha tocopherol during the same period. After slaughter, cured sausages were produced, packaged under three different atmospheric conditions, ripened for 4 weeks and then stored for 8 weeks (9 degrees C; 200 lux). The alpha-tocopherol content was recorded in the fat, liver, muscles and the sausage. TBARS, L*, a*, b* values and antioxidative capacity were evaluated in the sausage during storage. The results showed a transfer of vitamin E into tissues and sausage but no detectable effect on TBARS and colour stability. However, antioxidative effects of vitamin E were seen by provocation. Probably the effect of vitamin E in the sausage was masked by nitrite in the curing salt. The oxygen content of the packs had an influence on TBARS and colour stability. PMID- 22061992 TI - Carcass classification in suckling lambs. Discrimination ability of the European Union scale. AB - Forty-nine Manchega suckling lambs were used in this trial. Lambs were slaughtered at 10, 12 and 14 kg liveweight (cold carcass weight lower than 13 kg). The degree of fatness was assessed by three assessors on colour photographs of the carcasses, using the European Union scale for light lambs (EU), and another new scale developed in our laboratory (Suckling Lamb scale, SL). Carcass degree of fatness was reassessed using the same scales divided into 0.25 point intervals (EUI, SLI). Carcasses were allocated into four groups by means of a tree classification algorithm (cluster analysis), according to 27 variates, namely muscle percentage, whole fat percentage, subcutaneous fat, intermuscular fat, kidney knob and channel fat percentage and muscle percentage, both in the carcass and in three joints (leg, best end neck plus loin, and shoulder). SL scale groups showed a higher number of variates well correlated to assessors' scoring than EU scale groups. Nevertheless, the EU scale showed significant between-groups differences in a higher number of variates (P<0.01). Using 0.25 points interval scales, EUI scale scoring was the best correlated to tissue composition. However, most variates were better correlated to dorsal fat thickness measurement (4 cm back from last rib and 4 cm from the carcass midline) than to assessors' scoring. All four groups in the tree classification were statistically different from one another, but assessors only were able to detect differences between whole fat percentage in group 1 and the rest. These results suggest that it is possible to improve the photographic standards of the EU method by using a 0.25 points interval scale. In abattoir conditions, the new SL method (1.0 point intervals) proved to be better. Measure of dorsal fat thickness proved to be a very good predictor of carcass tissue composition, but it is a more expensive measure. PMID- 22061993 TI - Evaluation of pork colour sensory colour assessment using trained and untrained sensory panellists. AB - M. longissimus dorsi and M. psoas major minced pork patties from three dietary treatment groups of DLY (Duroc/Landrace/Yorkshire) cross bred pigs were packaged in polythene bags and placed in a retail refrigerated display cabinet at 5+/-1 degrees C, under fluorescent light (1000 lux) for up to 5 days. Each dietary treatment group consisted of pigs (n=7) fed either a low vitamin E diet (80 mg dl alpha-tocopheryl acetate/kg of feed), supplemental iron [7 g iron (II) sulphate/kg feed] or supplemental vitamin E (200mg dl-alpha-tocopheryl acetate/kg of feed)+supplemental iron. Samples were subjected to visual colour evaluation by a trained sensory panel (n=8) and an untrained panel (n=8) on days 0, 1, 3 and 5 of display. The signal to noise (S/N) ratios for assessors and replicates for the trained assessor group were higher than those of the untrained assessor group indicating greater reliability in the trained assessor results. The trained assessor group produced relatively normal percentile distributions for sensory terms in the assessment of both M. longissimus dorsi and M. psoas major muscles. The untrained assessor group displayed more skewed or non-symmetric distributions for M. longissimus dorsi, but produced a normal distribution for M. psoas major. Quantitative and qualitative analysis of the sensory profiling by both the trained and untrained groups of test subjects showed that in general sensory training contributed to a more effective visual sensory evaluation of M. longissimus dorsi in terms of metmyoglobin development. However, this is not the case for M. psoas major where both groups of assessors produced comparable results. Use of uniploar scaling did not improve the discriminative ability of assessors, both trained and untrained, in assessment of blue and yellow. The untrained group of assessors were even less effective in the use of these scales. It appeared that the sensory visual assessment of meat products can be performed effectively without training when the product colour is familiar to the assessors. However, training of panellists becomes relevant when a more unfamiliar product of unfamiliar colour is to be assessed and the unintuitive aspect of discrimination may play a greater role in the objective sensory colour assessment of meat. PMID- 22061994 TI - Phenotypic variations of muscle fibre and intramuscular fat traits in Longissimus muscle of F(2) population Duroc*Berlin Miniature Pig and relationships to meat quality. AB - In Longissimus muscle from a F(2) population of Duroc*Berlin Miniature Pigs, micro-structural fibre traits and fatty acid composition were investigated to calculate correlation coefficients between these traits and meat quality. The animals of the F(2) population exhibited low carcass weight (55.7+/-11.2 kg), low meat percentage (35.0+/-8.4%) but a relatively high intramuscular fat content (3.52+/-1.44%) compared to pure bred animals (F(0)). No unacceptable meat quality was observed. The variation coefficients of carcass composition, muscle fibre traits, and fat traits were high enough to allow the analysis of candidate genes which influence the growth of muscle fibres, fat cells, and meat quality. Phenotypic correlation coefficients between muscle fibre characteristics and meat quality traits were low whereas fatty acid composition and meat quality were more closely related. The correlation coefficients between muscle fibre traits and fatty acid composition ranged from 0.10 to 0.40. The relationship between a low quotient of n-6/n-3 fatty acids in muscle and greater fibre sizes, higher percentages of the oxidative fibre type and higher capillary density was noteworthy indicating good conditions for muscle growth and meat quality. PMID- 22061996 TI - Possible improvement of CBCT scan. PMID- 22061997 TI - Analysis of calcium signaling pathways in plants. AB - BACKGROUND: Calcium serves as a versatile messenger in many adaptation and developmental processes in plants. Ca2+ signals are represented by stimulus specific spatially and temporally defined Ca2+ signatures. These Ca2+ signatures are detected, decoded and transmitted to downstream responses by a complex toolkit of Ca2+ binding proteins that function as Ca2+ sensors. SCOPE OF REVIEW: This review will reflect on advancements in monitoring Ca2+ dynamics in plants. Moreover, it will provide insights in the extensive and complex toolkit of plant Ca2+ sensor proteins that relay the information presented in the Ca2+ signatures into phosphorylation events, changes in protein-protein interaction or regulation of gene expression. MAJOR CONCLUSIONS: Plants' response to signals is encoded by different Ca2+ signatures. The plant decoding Ca2+ toolkit encompasses different families of Ca2+ sensors like Calmodulins (CaM), Calmodulin-like proteins (CMLs), Ca2+-dependent protein kinases (CDPKs), Calcineurin B-like proteins (CBLs) and their interacting kinases (CIPKs). These Ca2+ sensors are encoded by complex gene families and form intricate signaling networks in plants that enable specific, robust and flexible information processing. GENERAL SIGNIFICANCE: This review provides new insights about the biochemical regulation, physiological functions and of newly identified target proteins of the major plant Ca2+ sensor families. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling. PMID- 22061998 TI - Alg14 organizes the formation of a multiglycosyltransferase complex involved in initiation of lipid-linked oligosaccharide biosynthesis. AB - Protein N-glycosylation begins with the assembly of a lipid-linked oligosaccharide (LLO) on the endoplasmic reticulum (ER) membrane. The first two steps of LLO biosynthesis are catalyzed by a functional multienzyme complex comprised of the Alg7 GlcNAc phosphotransferase and the heterodimeric Alg13/Alg14 UDP-GlcNAc transferase on the cytosolic face of the ER. In the Alg13/14 glycosyltransferase, Alg14 recruits cytosolic Alg13 to the ER membrane through interaction between their C-termini. Bioinformatic analysis revealed that eukaryotic Alg14 contains an evolved N-terminal region that is missing in bacterial orthologs. Here, we show that this N-terminal region of Saccharomyces cerevisiae Alg14 localize its green fluorescent protein fusion to the ER membrane. Deletion of this region causes defective growth at 38.5 degrees C that can be partially complemented by overexpression of Alg7. Coimmunoprecipitation demonstrated that the N-terminal region of Alg14 is required for direct interaction with Alg7. Our data also show that Alg14 lacking the N-terminal region remains on the ER membrane through a nonperipheral association, suggesting the existence of another membrane-binding site. Mutational studies guided by the 3D structure of Alg14 identified a conserved alpha-helix involved in the second membrane association site that contributes to an integral interaction and protein stability. We propose a model in which the N- and C-termini of Alg14 coordinate recruitment of catalytic Alg7 and Alg13 to the ER membrane for initiating LLO biosynthesis. PMID- 22061999 TI - Production of active human glucocerebrosidase in seeds of Arabidopsis thaliana complex-glycan-deficient (cgl) plants. AB - There is a clear need for efficient methods to produce protein therapeutics requiring mannose-termination for therapeutic efficacy. Here we report on a unique system for production of active human lysosomal acid beta-glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45) using seeds of the Arabidopsis thaliana complex-glycan-deficient (cgl) mutant, which are deficient in the activity of N acetylglucosaminyl transferase I (EC 2.4.1.101). Gaucher disease is a prevalent lysosomal storage disease in which affected individuals inherit mutations in the gene (GBA1) encoding GCase. A gene cassette optimized for seed expression was used to generate the human enzyme in seeds of the cgl (C5) mutant, and the recombinant GCase was mainly accumulated in the apoplast. Importantly, the enzymatic properties including kinetic parameters, half-maximal inhibitory concentration of isofagomine and thermal stability of the cgl-derived GCase were comparable with those of imiglucerase, a commercially available recombinant human GCase used for enzyme replacement therapy in Gaucher patients. N-glycan structural analyses of recombinant cgl-GCase showed that the majority of the N glycans (97%) were mannose terminated. Additional purification was required to remove ~15% of the plant-derived recombinant GCase that possessed potentially immunogenic (xylose- and/or fucose-containing) N-glycans. Uptake of cgl-derived GCase by mouse macrophages was similar to that of imiglucerase. The cgl seed system requires no addition of foreign (non-native) amino acids to the mature recombinant GCase protein, and the dry transgenic seeds represent a stable repository of the therapeutic protein. Other strategies that may completely prevent plant-like complex N-glycans are discussed, including the use of a null cgl mutant. PMID- 22062000 TI - Functional roles of effectors of plant-parasitic nematodes. AB - Plant pathogens have evolved a variety of different strategies that allow them to successfully infect their hosts. Plant-parasitic nematodes secrete numerous proteins into their hosts. These proteins, called effectors, have various functions in the plant cell. The most studied effectors to date are the plant cell wall degrading enzymes, which have an interesting evolutionary history since they are believed to have been acquired from bacteria or fungi by horizontal gene transfer. Extensive genome, transcriptome and proteome studies have shown that plant-parasitic nematodes secrete many additional effectors. The function of many of these is less clear although during the last decade, several research groups have determined the function of some of these effectors. Even though many effectors remain to be investigated, it has already become clear that they can have very diverse functions. Some are involved in suppression of plant defences, while others can specifically interact with plant signalling or hormone pathways to promote the formation of nematode feeding sites. In this review, the most recent progress in the understanding of the function of plant-parasitic nematode effectors is discussed. PMID- 22062001 TI - Molecular cloning and functional characterization of the porcine extracellular domain of Receptor Activator of NF-kappaB Ligand (sRANKL). AB - Receptor Activator of NF-kappaB Ligand (RANKL) plays a pivotal role as a regulator of osteoclast activity and is involved in osteoporosis. Here, we report the cloning and functional characterization of the complete extracellular domain of the porcine RANKL gene (sRANKL). The porcine sRANKL cDNA has an ORF of 744 nucleotides and shares 87%, 80% and 80% identity with human, rat and mouse RANKL coding sequences, respectively. The protein consists of 247 amino acids with 90%, 81% and 80% sequences similarities compared to human, mouse and rat RANKL, respectively. Over-expression of porcine sRANKL led to osteoclast formation. The osteoclasts showed a characteristic morphology, expressed the carbonic anhydrase type 2, were TRACP positive and exhibited a bone-resorbing activity. In conclusion, we first describe the molecular cloning and functional characterization of porcine sRANKL, which will help to understand the function of a RANKL gene in large animal models. PMID- 22062002 TI - Irradiation effects on meat color - a review. AB - Color changes in irradiated fresh meat occur because of the susceptibility of the myoglobin molecule, especially the iron, to alterations in the chemical environment and to energy input. The potential for iron electrons to exist in various states makes the environment adjacent to the iron atom particularly vulnerable to the presence of electron-donating compounds and high energy inputs (irradiation). Initial condition of the myoglobin (Fe(++)?O(2), Fe(+++)), modification of oxidation-reduction potential of the tissue, and generation of ligand-forming compounds (CO) from endogenous organic compounds and water are enhanced or suppressed depending on the gas atmosphere, temperature, pH and myoglobin concentration of the system. Generation of stable red pigments or brown pigments which become red over time appears to be due to binding of irradiation generated reactive oxygen species (()O(2)(-)) or gasses (CO) which become ligands bound by iron under altered reducing conditions. Rapid generation of large amounts of metmyoglobin when irradiation is conducted in an oxygen-containing environment appears to be an acceleration of the normal process by which myoglobin undergoes oxidation. Generation of green pigments appears to be due to breakdown of the porphyrin integrity and/or formation of sulfmyoglobin. Maintenance of ideal meat color during irradiation can be enhanced by various combinations of pre-slaughter feeding of antioxidants to livestock, optimizing the condition of the meat prior to irradiation, addition of antioxidants, gas atmosphere (MAP), packaging, and temperature control. PMID- 22062003 TI - Effect of vitamin E, low dose irradiation, and display time on the quality of pork. AB - A 4*2*3 factorial experiment was designed to investigate the effect of supplemental vitamin E (0, 100, 200, and 300 mg/kg feed), irradiation and days in display on quality characteristics of aerobically packaged ground pork and vacuum packaged loin chops. Color, thiobarbituric acid reactive substances (TBARS), olfactory and sensory characteristics were evaluated. Samples held in display for 3 d were used for sensory evaluation. In the ground pork, irradiation (1.9 kGy) increased "wetdog" flavor, increased a(*) (redness) and decreased L(*) (lightness) and b(*) (yellowness) values but had no effect on TBARS. However, as display time (0, 4, and 8 days) increased; the differences in a(*) values diminished and putrefying and fishy odors were higher in non-irradiated samples than irradiated. Supplemented vitamin E had no effect on TBARS, odor, and color measures; but increased the juiciness of ground pork regardless of irradiation. Similarly, in the loin chops, irradiation (1.5 kGy) increased a(*) value and "wetdog" flavor; but decreased b(*) value regardless of vitamin E supplementation. Also, irradiation reduced putrefying, and fishy odors during longer display times. TBARS increased with increased display time but was not affected by vitamin E supplementation. These results indicate that in aerobically packaged ground pork and vacuum packaged loin chops, radiolytic odors and color changes cannot be mediated with vitamin E supplementation. Display time and irradiation are significant in determining color and odor changes. PMID- 22062004 TI - A comparison of the aroma volatiles and fatty acid compositions of grilled beef muscle from Aberdeen Angus and Holstein-Friesian steers fed diets based on silage or concentrates. AB - This paper compares the volatile compound and fatty acid compositions of grilled beef from Aberdeen Angus and Holstein-Friesian steers slaughtered at 14 months, each breed fed from 6 months on either cereal-based concentrates or grass silage. Linoleic acid levels were higher in the muscle of concentrates-fed animals, which in the cooked meat resulted in increased levels of several compounds formed from linoleic acid decomposition. Levels of alpha-linolenic acid, and hence some volatile compounds derived from this fatty acid, were higher in the meat from the silage-fed steers. 1-Octen-3-ol, hexanal, 2-pentylfuran, trimethylamine, cis- and trans-2-octene and 4,5-dimethyl-2-pentyl-3-oxazoline were over 3 times higher in the steaks from the concentrates-fed steers, while grass-derived 1-phytene was present at much higher levels in the beef from the silage-fed steers. Only slight effects of breed were observed. PMID- 22062005 TI - Effect of vitamin C addition to ground beef from grass-fed or grain-fed sources on color and lipid stability, and prediction of fatty acid composition by near infrared reflectance analysis. AB - Research was conducted to determine the effect of postmortem vitamin C addition (VITC) versus no VITC (CONTROL) to ground beef from grass-fed (GRASS) or grain fed (GRAIN) sources on color and lipid stability during 8 days of illuminated display at 4 degrees C. The use of near-infrared reflectance (NIR) spectroscopy to predict the fatty acid composition of ground beef and its potential to discriminate samples from different nutritional backgrounds were also evaluated. Total lipid content of ground beef was 53% lower (P<0.05) for GRASS than GRAIN. Ground beef from GRASS had greater (P<0.01) percentages of saturated (SFA) and polyunsaturated (PUFA) fatty acids, and lower (P<0.01) percentages of monounsaturated (MUFA) fatty acids than GRAIN. For GRAIN, VITC reduced (P<0.01) lipid oxidation, and resulted in darker (P<0.01) and redder (P<0.01) color of the ground beef from 2 to 8 days of display compared to CONTROL. For GRASS, lipid oxidation did not differ (P>0.05) for VITC and CONTROL. VITC improved (P<0.01) color stability by prolonging more red color in GRASS during 8 days of display. Results from partial least squares modeling showed accurate predictions using NIR for total saturated [standard error of performance (SEP=1.16%), coefficient of determination on the validation set (r(2)=0.87)] and unsaturated (SEP=1.18% and r(2)=0.90) fatty acid contents of ground beef, as well as the composition of stearic, oleic, and linolenic (SEP=1.2%, 1.27%, and 0.07%; r(2)=0.91, 0.92, and 0.93, respectively). However, the composition of other individual fatty acids was poorly predicted. VITC was effective in retarding pigment oxidation in ground beef from both GRAIN and GRASS; however, VITC reduced lipid oxidation in GRAIN samples only, despite higher PUFA percentages in GRASS. NIR can be used to predict accurately the content of total saturated and unsaturated, and stearic, oleic, and linolenic fatty acids in ground beef. NIR showed potential to discriminate meat samples originating from different feeding production systems. PMID- 22062006 TI - Sensory characteristics of Iberian ham: Influence of salt content and processing conditions. AB - Sensory characteristics of Semimembranosus and Biceps femoris muscles from 24 dry cured Iberian hams were assessed. Hams were salted with different amounts of salt (6% and 3% w/w) and then ripened at different temperature conditions (traditional processing vs. modified processing). Hams manufactured using modified processing showed higher scores for dryness (P<0.05), hardness (P<0.05) and rancid flavour (P<0.001) in the Semimembranosus muscle than those processed in a traditional way. The Biceps femoris muscle of hams salted with 6% of salt was drier (P<0.05), harder (P<0.05) and more fibrous (P<0.01) than in hams salted with 3% salt. Salty taste was more intense in the Semimembranosus and Biceps femoris from hams with a higher level of salt (P<0.01 and P<0.001, respectively). A more intense rancidity in hams ripened in modified processing could affect the overall aroma. A decrease in salt content produces less salty hams, but the changes in texture traits should be also considered. PMID- 22062007 TI - Influence of dietary lysine level, pre-slaughter fasting, and rendement napole genotype on fresh pork quality. AB - Sixty-four gilts from a commercial hybrid line were selected based on rendement napole (RN) genotype and live weight to evaluate the effects of feeding a lysine deficient diet and feed withdrawal prior to slaughter on fresh pork quality. Glycolytic potential was measured and the bimodal distribution was utilized to predict RN genotype. Diets containing 4.8 (deficient) or 6.4 g/kg lysine were fed for the last six weeks prior to slaughter. Feed withdrawal treatments were imposed 12 or 36 h prior to slaughter. The lysine-deficient diet increased intramuscular fat content; however, feed withdrawal did not consistently impact fresh pork quality. Pork from RN carriers had a lower ultimate pH and Hunter L(*). Results from this study suggest that feeding a lysine-deficient diet can increase the intramuscular fat content of both RN genotypes, but feed withdrawal did not impact pork quality. PMID- 22062008 TI - Reducing toughness of beef from Bos indicus draught steers by injection of calcium chloride: Effect of concentration and time postmortem. AB - Calcium chloride (CaCl(2)) solution in concentrations of 0, 0.2, 0.3 and 0.4 M was injected at 10% (wt/wt) either 45 min or 24 h postmortem into longissimus dorsi muscles of eight draught steers discharged from work and >4 years of age. Shear force, after 7 days of aging, declined by CaCl(2) injection by up to 50% of control, depending on CaCl(2) concentration. Prerigor treatment was twice as efficient as postrigor injection. Collagen content and solubility were less clearly affected. Sensory tenderness scores were higher by 50% with all CaCl(2) concentrations, but only with prerigor treatment. A bitter taste was noted only with the highest concentration of CaCl(2), but overall acceptance did not increase with CaCl(2) concentration. CaCl(2) enhanced electrical conductivity, reduced redness and luminosity, and increased drip and thawing loss, but not boiling loss, of longissiumus dorsi. Results indicate a high potential of CaCl(2) treatment in extraordinarily tough meat. PMID- 22062009 TI - Fatty acids and triacylglycerols profiles from different types of Iberian dry cured hams. AB - Thirty hams were allotted into four groups according to fattening diet ("Montanera" - acorns and pasture; and "Pienso" - concentrated diet) and genotype of pigs (Iberian and Iberian*Duroc pigs). Total lipids, triacylglycerol composition and fatty acids from neutral lipids fraction were measured in biceps femoris muscle. Fattening diet largely affected lipid composition of hams. Total intramuscular lipids and triacylglycerols content were higher in Montanera hams than in Pienso hams. In Montanera hams, triacylglycerols contained more oleic acid (C18:1) and less stearic (C18:0) and palmitic (C16:0) acids (p<0.001) and accordingly less PSO, PPL, PPO, PPS, SSO (p<0.001) and more OLL, OOL, OOO triacylglycerols compared to Pienso hams (p<0.001). Genotype of pigs has an important effect in triacylglycerols composition but only a limited effect on their fatty acids composition. So, Iberian hams contained more of PLLn, PLL, POLn and POL+SLL compared to Iberian*Duroc hams (p<0.001) and POO and SOO were present in a higher quantity in Iberian*Duroc hams (p<0.01). PMID- 22062010 TI - Physicochemical, functional and microbiological quality of buffalo liver. AB - Buffalo liver is an important edible meat byproduct. However, in developing countries including India, it has a low commercial value and is underutilized. The present investigation was conducted to provide basic information on physicochemical, functional and microbiological quality of buffalo liver. Proximate composition was: moisture - 71.92%, protein - 18.44%, fat - 5.60%, carbohydrate - 2.72%, total ash - 1.32% and total energy - 135 kcal. Mineral concentrations (mg%) in liver were: Na - 60.04, K - 274, Ca - 5.60, Mg - 6.20, Fe - 20.86 and Cu - 5.60. Mean glycogen (mg/g), total liver pigments (mg/g) and cholesterol (mg%) were 7.07,8.49 and 283.88, respectively. The mean pH values of buffalo liver was 6.42, WHC - 38 ml per 100 g and cooking yield was 73.15%. Protein extractability studies indicated that liver contains higher amounts of water-soluble proteins (20-40%) than salt soluble proteins (7-15%) and presence of high molecular weight proteins in salt soluble protein fractions. The average microbial counts (log(10) cfu/g) for different organisms were APC - 6.10; psychrotrophs - 4.30; enterobacteriaceae counts - 4.97; staphylococcal counts 2.50 and total coliforms - 2.82. PMID- 22062011 TI - The effect of fructooligosaccharides on the sensory characteristics of cooked sausages. AB - The effect of a short chain fructooligosaccharide on the sensory properties of conventional and reduced-fat cooked meat sausages has been studied in products in which a fat reduction of close to 40% was obtained. The fibre assayed was used in sufficient amounts to constitute between 2% and 12% of the final product. The energy value reduction of the final products was close to 35%. Instrumental measurements of colour and texture were performed. Sensory properties were estimated by a hedonic test. A correlation principal component analysis was performed. The results showed that the sensory and textural properties and the overall acceptability were very good, which indicated that this fibre can be considered a good fat replacer in meat products. Thus, with its addition, a reduced calorie product enriched with soluble dietetic fibre is obtained. PMID- 22062012 TI - Colour of subcutaneous adipose tissue and M. longissimus dorsi of high index dairy and beef*dairy cattle slaughtered at two liveweights as bulls and steers. AB - The objectives of this study were (a) to compare muscle and adipose tissue colour of male progeny of two strains of high genetic merit Friesian cows (New Zealand [NZF] and Irish [DAF]) with those of beef (Belgian Blue)*dairy (Holstein Friesian) [BBHF] male progeny; (b) to compare bulls and steers (gender) of these genotypes and (c) to examine the effects of slaughter weight (SW) on these quality traits. Bulls (n=48) and steers (n=48) of the three genotypes were grown to nominal target liveweights of 550 kg (light) and 630 kg (heavy). Adipose tissue from the NZF genotype was more yellow (P<0.05) than from DAF or BBHF, regardless of gender or SW. For longissimus dorsi (LD) pH, bulls and heavy animals had higher pH (P<0.05) than steers or light animals, respectively, while NZF and BBHF bulls had higher pH than steers. LD muscle from the BBHF genotype had lighter colour (P<0.05) and lower haem pigments (P<0.01) than NZF or DAF progeny. There was no difference in muscle 'L' value between light bulls and steers but heavy bulls had darker muscle than heavy steers. There was an interaction between genotype, gender and SW for LD redness. Thus, NZF animals were most red when slaughtered as light or heavy bulls, but there were no differences between genotypes slaughtered as light or heavy steers. These data demonstrate differences in colour of beef, especially from progeny of NZF, which produced the most yellow adipose tissue and the most red muscle tissue. PMID- 22062013 TI - Quantification of salt concentrations in cured pork by computed tomography. AB - Eight pork loin samples were mounted in Plexiglas cylinders and cured for five days. Samples were scanned by computed tomography (CT) once every 24 h. At the end of the experiment, the cylinders were cut in 1 cm sections and analyzed for chloride. From image analysis of the CT images, concentration profiles were extracted and fitted to a diffusion model which included a term to account for a non-negligible mass transfer coefficient. It was found that CT provides accurate estimates of salt gradients in meat and it was suggested that this analytical method could be valuable in scientific research and product development. PMID- 22062014 TI - Shelf life characteristics of enhanced modified atmosphere packaged pork. AB - The objective of these studies was to identify a chemical indicator for predicting performance of enhanced pork during storage, then select raw materials with the potential for color and shelf life instability and enhance them with antimicrobial solutions in an attempt to overcome their initial deficits. The purpose of Study 1 was to evaluate the use of pH, glycolytic potential, and glucose levels in the drip to assess shelf life characteristics of modified atmosphere packaged (MAP), enhanced pork loin chops during display. Chops from higher pH carcasses had higher color scores and aerobic plate counts, and less discoloration. Study 2 evaluated shelf life characteristics of chops derived from high pH (>5.75) raw materials enhanced with solutions containing salt and phosphate, and/or lactate and/or acetate. Overall, pH was the best indicator of color and microbiological stability. Raw materials with high ultimate pH were least stable. MAP chops derived from high pH raw materials and enhanced with a sodium acetate-containing solutions had better color and microbiological shelf life than those enhanced with other solutions. PMID- 22062015 TI - A note on histamine levels in Turkish style fermented sausages. AB - The histamine contents of Turkish style fermented sausages were determined on 46 samples of five different brands obtained from retail stores in Van in Turkey. Histamine was found in all samples in the range 19.64-87.47 mg/kg (mean 32.13 mg/kg). Histamine levels in the brands differed significantly (P<0.01). The results suggest that the histamine levels in the sausages were not hazardous in terms of public health although they may be a potential risk to sensitive individuals. PMID- 22062016 TI - Analytical limits of total and insoluble collagen content measurements and of type I and III collagen analysis by electrophoresis in bovine muscles. AB - Three to 16 animals were necessary to detect a difference of 50-20% in total collagen contents in Longissimus thoracis muscle, between two experimental groups of cattle, using the facilities available in our laboratory. The inter-assay variability was higher for insoluble collagen content than for total collagen content. Consequently differences between two groups are determined less accurately for insoluble collagen content than for total collagen content. This may be partly compensated by repeated measurements (minimum 4) to detect a difference of 40% or even higher. The low reproducibility of type I and type III collagen contents determined by electrophoretic analysis is due to uncontrollable technical parameters. Normalisation of the results is thus necessary for accurate quantification. The recommended procedure is to use total protein content detected and quantified on the gels as a covariable in the statistical model. This procedure induces a 15% reduction in intra-subject variability, and hence in sample size required to detect significant differences. PMID- 22062017 TI - A sensory map of the meat universe. Sensory profile of meat from 15 species. AB - The aim of the study was to investigate if meat from different species could be described and related to each other by sensory analysis. Muscle meat from 15 different species commercially available in Norway was assessed by a 22 sensory attribute profile and analysed by multivariate analysis. The different species were significantly different on attributes that gave adequate descriptions of all species. Sixty-eight percent of the sensory variation was contained in the first component, which was dominated by colour attributes. In a model where colour was removed, odour and flavour were the most important attributes accounting for 66% and texture attributes, which accounted for only 13%. PMID- 22062018 TI - Methods to increase tenderness of individual muscles from beef rounds when cooked with dry or moist heat. AB - Muscles (n=9) from beef rounds (n=40) were subjected to one of the four tenderization strategies: control, blade tenderization, enzymatic tenderization or salt/phosphate injection. Treated muscles were aged, cut into steaks, cooked using one of the two cooking methods (dry-heat or moist-heat), and Warner Bratzler shear (WBS) force values were determined. For dry-heat cookery, injection with a salt and phosphate solution resulted in the lowest WBS values, however, WBS values for blade tenderization and enzymatic tenderization were comparable in the M. adductor, M. vastus lateralis, M. rectus femoris, and M. semimembranosus (cranial and caudal aspects). The M. gluteobiceps (cranial and caudal aspects, and ischiatic head) and M. semitendinosus showed little improvement in WBS values with any of the tenderization treatments. For moist heat cookery, only the M. rectus femoris and M. semimembranosus, caudal aspect, showed significant decreases in WBS values, and those improvements were only associated with salt and phosphate injection and enzymatic tenderization. Within each cooking method and tenderization treatment, the M. rectus femoris, M. semimembranosus, cranial aspect had the lowest WBS values, whereas the M. gluteobiceps, ischiatic head and M. semimembranosus typically had the highest WBS values. All tenderization strategies increased the frequency of muscles being rated as "very tender" (WBS<31.4 N) and "tender" (31.4 N0.05) were noted in sulphydryl content under the same conditions. The increase in deamidation resulted in a decrease in hydrophobicity and an increase in protein solubility. gamma-irradiation also reduced the number of microorganisms in the meat. Mesophiles were more resistant to the irradiation treatment than psychrotrophs and Pseudomonas. All irradiated pork samples (1 or 3 kGy) had a bacterial count lower that 10(7) CFU/g after 15 days of storage. A minimal dose of 1 kGy was sufficient to increase the shelf life of fresh pork loins although variations in initial pork contamination was found to be the determining factor accounting for the effectiveness of the treatment. PMID- 22062031 TI - Lipid oxidation, color changes and volatiles production in irradiated pork sausage with different fat content and packaging during storage. AB - Effects of irradiation on lipid oxidation, color and volatiles production in pork sausages with different fat content and packaging were determined. Sausages (with 4.7, 10.5 and 15.8% fat content) were sliced and vacuum-packaged either in oxygen permeable or impermeable bags, irradiated (0 or 4.5 kGy) and stored at 4 degrees C for 7 days. Lipid oxidation, color and volatiles productions were analyzed at 0, 3 and 7 days of storage. TBARS (2-thiobarbituric acid reactive substances) values of cooked pork sausages increased with the increase of fat content regardless of storage, irradiation or packaging types. Irradiated samples had higher TBARS than nonirradiated at 0 day but the difference disappeared during storage in both packaging types. Lightness of sausages (Hunter L-value) increased with the increase of fat content and storage time but was not affected by irradiation. In aerobic packaging, irradiation reduced Hunter a-values of pork sausages at 0 day but irradiation effect on a-value disappeared during storage. In vacuum packaging, however, irradiated samples had higher Hunter a-values than nonirradiated samples. Irradiation increased 1-heptene and total volatiles, but the amount of 1-heptene was not associated well with TBARS values of pork sausages. In both irradiated and nonirradiated pork sausages, aerobic packaging produced more volatiles than vacuum packaging during storage. It was concluded that irradiation and fat content had significant effects on lipid oxidation, color and volatiles production of cooked pork sausages during storage but that oxygen availability had a stronger effect than irradiation and fat content. PMID- 22062032 TI - Textural effect of chilling hot Longissimus dorsi muscle with solid CO(2). AB - This paper covers the work carried out on the textural effects of chilling hot boned meat using solid carbon dioxide (CO(2)). The purpose was to measure the texture of beef Longissimus dorsi (LD) chilled in boxes with solid CO(2) and to compare this with conventionally chilled meat. The results showed that CO(2) chilled meat were tougher than the controls. Shear force (SF) and work done (WD) results indicated that 63% of the CO(2) chilled meat were above 50N compared to 32% of the controls, taste panel would judge this as slightly tough. 22% of the CO(2) chilled meat was SF>100N which overall would be judged as extremely tough as compared to 2% of the controls. The work also showed that the laser diffraction technique was unable to distinguish between active and passive shortening giving only an average or overall length for the area viewed. PMID- 22062033 TI - Injection of water and polyphosphate into pork to improve juiciness and tenderness after cooking. AB - Two injection levels (5 and 10%) and three concentrations of polyphosphate (0, 3 and 5%) were used in 64 pork loin portions to assess the influence of polyphosphate injection on eating quality of pork steaks cooked by grilling to a centre temperature of 72.5 or 80 degrees C and assessed by a trained ten member sensory panel. Polyphosphate improved water holding, and generally produced more tender and more juicy meat than control steaks, although pork flavour intensity was reduced and abnormal flavour intensity increased. Raising the centre temperature from 72.5 to 80 degrees C increased the cooking loss from 35 to 42%, reduced tenderness, juiciness and abnormal flavours and increased pork flavour intensity. Steaks containing 5% polyphosphate and cooked to 80 degrees C were more tender and as juicy as steaks without polyphosphate cooked to the lower centre temperature. These effects were generally larger than those that can be achieved 'naturally' by, for example, changing diets and breeds but whether the technology will be utilised in an increasingly 'additive free' climate is debatable. PMID- 22062034 TI - Sodium chloride levels in comminuted chicken muscle in relation to processing characteristics and Fresnel reflectance detected with a polarimetric probe. AB - Increasing NaCl from 0 to 2% in comminuted samples of chicken breast meat increased the resistance to compression of cooked samples (r=0.98, p<0.001), increased water-holding capacity (r=0.95, p<0.001), decreased cooking losses (r= 0.97, p<0.001) and decreased paleness (L(*)) before and after cooking (r = -0.96 and r=-0.99, respectively, p<0.001). The decrease in paleness caused by NaCl was associated with an increase in the relative amount of reflected light maintaining its original plane of polarisation, so that NaCl% was correlated with an extinction coefficient for polarised light, r=0.91, p<0.001. A possible explanation is that myofibrillar proteins may have been dissolved at high levels of NaCl, thus reducing light scattering by myofibrils and allowing more Fresnel reflectance to be detected. PMID- 22062035 TI - Breed type and ageing time effects on sensory characteristics of beef strip loin steaks. AB - Forty-two yearling males from seven European beef breeds were used to study breed type and ageing time effects on meat sensory quality. Breeds were grouped according to their double muscled condition (DM), dual-purpose condition (Brown Swiss, BS), fast growth rate (FG) and rustic characteristics (RT). Vacuum packaged loin chops were aged for 1, 3, 7, 10, 14 and 21 days at 4 degrees C and evaluated by a trained taste panel. Ageing time had the main influence in all the studied sensorial descriptors. Breed type did not affect juiciness, fibrosity or overall flavour intensity. Interactions between breed type and ageing appeared in global odour intensity, tenderness (p<0.05) and acid flavour intensity (p<0.01). All breed types showed higher tenderness scores as ageing period increased but, comparatively, those with higher scores at an early postmortem period (DM, FG) showed lower scores at a late postmortem time. A possible faster, but shorter and less intensive meat tenderisation rate in animals with double muscled condition, and its particular collagen characteristics, in relation to BS and RT groups, could explain our findings. PMID- 22062036 TI - Influence of loading method and stocking density during transport on meat and dry cured ham quality in pigs with different halothane genotypes. AB - The effect of loading method and stocking density in transit on meat and dry cured ham quality was investigated in pigs with different halothane genotypes. A total of 507 Italian heavy pigs, supplied by two farms, were loaded by ramp or lift and transported unmixed for 35-55 min to the abattoir at a stocking density of either <0.4 or >0.6m(2) per 100 kg pigs. After overnight lairage in separate pens with free access to water, the pigs were slaughtered. Halothane genotype was assessed post mortem. Four hundred and thirty-nine pigs had a homozygous dominant (NN) genotype and 68 pigs were heterozygous (Nn). Carcass skin damage, meat quality traits and ham curing parameters were evaluated. Loading method and stocking density showed a negligible effect on meat and dry-cured ham quality while the predominant factor affecting these was the halothane genotype. Nn pigs produced meat with a faster rate of pH fall and lower water holding capacity as well as ham with higher weight losses in salting and greater incidence of defects in the dry-cured product. There were insignificant interactions between halothane genotype and loading method or stocking density. Overall, irrespective of pre slaughter treatment, the Nn pigs were less suitable for the production of high quality products such as dry-cured ham. PMID- 22062037 TI - Furosine as an index of heat treatment intensity in meat products: Its application to cooked ham. AB - Furosine, a product of acid hydrolysis of Amadori compounds, has been proposed as an index of the heat treament intensity in various food products. In this paper we suggest furosine as an index of heat treatment in pork-meat products as well. Furosine is not detectable in fresh raw pork muscle and in injected tumbled pork muscle, the latter being used for the production of cooked ham. Activation energy of furosine formation in raw muscle and tumbled muscle, in the temperature range of 70 degrees -90 degrees C, was 79.2 kJ/mole and 81.7 kJ/mole, respectively. Furosine concentration was assessed in cooked hams whose time-temperature profiles, with reference to the cooking and cooling processes, were well known, thus enabling the verification of the feasibility of its use in the evaluation of heat damage. The good correlation between the values found during this investigation and the values foreseen by kinetic calculation confirms that furosine can be used as an index of heat treatment intensity in the production of cooked ham. PMID- 22062038 TI - Investigations into the accuracy of prediction of beef carcass composition using subcutaneous fat thickness and carcass weight I. Identifying problems. AB - Investigations were conducted into the accuracy of prediction of the percentages of fat and muscle in 69 steer carcasses using subcutaneous fat thickness and carcass weight. The carcasses were arbitrarily divided into low and high fat thickness, and light and heavy weight categories. Relationships between fat thickness and the percentages of fat and muscle were modified by breed and weight group (or their interactive effects), or by breed and fat group (or their interactive effects). General equations ignoring breed should not, therefore, be used for prediction. The equations were modified by using low and high fat thickness or light and heavy carcass weight groups. Because of the absence of breed differences in the lighter weight and lower fat thickness groups, a single breed-ignored regression equation could be used in each case to predict the carcass components. In the fatter and heavier groups of carcass significant breed differences occurred and breed specific regression equations should be used. PMID- 22062039 TI - Investigations into the accuracy of prediction of beef carcass composition using subcutaneous fat thickness and carcass weight II. Improving the accuracy of prediction. AB - Attempts were made to improve the accuracy of prediction of carcass components in 68 steer carcasses using a subcutaneous fat thickness measurement (FTP(8)) and hot side weight as the principal or sole predictors. When carcasses were divided into two weight ranges, prediction of the percentages of carcass fat (fat %) and muscle (muscle %) in the lighter group, using FTP(8), were almost as accurate (fat %: RSD, 1.83; R(2), 0.73; muscle %: RSD, 1.70; R(2), 0.47) as those given by multiple regression measurements made by advanced technologies. Prediction in the heavier weight group was unsatisfactory, featuring high RSDs and a low R(2). Because breed differences in prediction did not occur in the lighter group, a single prediction equation could be used for each carcass component. The use of fat thickness groups gave a similar result to that of weight groups. Once weight groups were used, curvilinear analysis did not improve the accuracy of prediction. In the lighter carcasses, the addition of hot side weight, eye muscle area and muscle score, singly or in combination, did not improve the accuracy of percentage predictions. In the heavier carcasses, the addition of hot side weight and eye muscle area was necessary to give prediction of a modest level of accuracy. For the prediction of the weights of carcass components, the addition of hot side weight to FTP(8) gave the most accurate prediction in light carcasses (fat weight: RSD, 1.60; R(2), 0.92; muscle weight: RSD, 2.08; R(2), 0.97). In the heavy carcasses, hot side weight and eye muscle area added to FTP(8) gave the most accurate prediction (fat weight: RSD, 4.40; R(2), 0.69; muscle weight: RSD, 3.73; R(2), 0.88). Because of the high level of variance explained, it is recommended that weights of carcass components be predicted, particularly in heavy carcasses. PMID- 22062040 TI - Influence of slaughter weight and stress gene genotype on the water-holding capacity and protein gel characteristics of three porcine muscles. AB - The longissimus lumborum, gluteus medius, and the triceps brachii muscles from 40 animals were used to evaluate the effect of stress gene genotype (non-mutant, NN and mono-mutant, Nn) and live weight at slaughter (110 kg and 140 kg) on the processing quality of fresh pork. The 45 minute and ultimate pH measurements did not differ between genotypes. Total percent protein was not different between samples taken from NN or Nn pigs, nor were there any differences in salt-soluble protein. The M. longissimus lumborum from Nn pigs possessed lower water-holding capacity values and lost greater amounts of water upon cooking. In addition, Nn pigs had lower subjective color and firmness scores which suggest a higher incidence of pale, soft and exudative pork. Slaughter weight did not affect total protein, salt-soluble protein, Minolta L(*), a(*) and b(*) values or subjective color, firmness and marbling scores. Back fat thickness and loineye area increased as slaughter weight increased. Overall, this study suggested that Nn pigs have reduced water retention properties which may result in lower yields in processed meat items. Slaughter weight had limited effects on the processing quality of meat from NN or Nn pigs. There were no interactions of significance between stress gene genotype and slaughter weight, suggesting that the differences in muscle quality and functional properties between NN and Nn pigs are maintained over the slaughter weights used in this study. PMID- 22062041 TI - Lipid oxidation induced by oxymyoglobin and metmyoglobin with involvement of H(2)O(2) and superoxide anion. AB - The role of oxymyoglobin oxidation in lipid oxidation was studied in a myoglobin liposome system. The pro-oxidant effect of oxymyoglobin towards lipid oxidation was concentration-dependent. At equimolar concentrations, oxymyoglobin showed higher pro-oxidative activity towards lipid than metmyoglobin (p < 0.05). These results suggested that the process of oxymyoglobin oxidation is involved in catalyzing lipid oxidation. The addition of catalase into the oxymyoglobin liposome system resulted in significantly decreased oxidation of oxymyoglobin and lipid (p < 0.05) suggesting a role for H(2)O(2) in the interaction between oxymyoglobin and lipid. The addition of Superoxide dismutase was without effect (p > 0.05) suggesting that Superoxide anion was not directly involved in mediating oxidation of oxymyoglobin and lipid. Albumin was added as a control for a non-specific protein antioxidant; it did not affect oxymyoglobin or lipid oxidation (p > 0.05). Our in vitro results support the hypothesis that the actual process of oxymyoglobin oxidation is a catalyst of lipid oxidation with H(2)O(2) a major factor. PMID- 22062042 TI - Oxidation in pre-cooked minced pork as influenced by chill storage of raw muscle. AB - During storage for four days at 4 degrees C of pre-cooked minced pork, lipid oxidation measured as thiobarbituric acid reactive substances (TBARS) and as hexanal by solid phase microextraction was found to depend on the level of lipid hydroperoxides rather than on the TBARS in the raw muscle (M. Longissimus dorsi). Storage for up to six days at 4 degrees C, prior to mincing and cooking, resulted in a decrease in lipid hydroperoxides measured as conjugated dienes and in increasing TBARS-value in the raw muscle, and in a pre-cooked product with better oxidative stability. The correlation coefficient between accumulation of TBARS and hexanal in the pre-cooked meat was 0.98, indicating that the new technique using solid phase microextraction with subsequent GC-analysis for determination of hexanal can be used as an alternative technique to describe lipid oxidation in pre-cooked meat. PMID- 22062043 TI - Inhibitory effect of sulfur-containing amino acids on burnt off-flavours in canned liver sausages. AB - The sensory quality of canned liver sausages is limited by a negative burnt high temperature-heated flavour, caused by Maillard reaction products between amino acids and sugars. In experiments with liver sausage, reduced glutathione in concentrations of 0.01-0.30% had no positive effect on taste and color. N-acetyl L-cysteine, an acylated derivative of the amino acid L-cysteine, was tested in concentrations between 0.03-0.50%; a concentration of 0.15% was optimal for the inhibition of the burnt flavour. An acid taste caused by lower pH was corrected by the addition of 0.25% diphosphate. When 0.15% N-acetyl-L-cysteine and 0.25% diphosphate were added to the sausage preparations, the heat-induced changes in amino acids and glucose were the same as in the control. Moreover, under different sterilization conditions, the additive mixture was shown to be an excellent inhibitor of the burnt flavour. PMID- 22062045 TI - The role of mitogen activated protein kinase signaling in microglia and neurons in the initiation and maintenance of chronic pain. AB - Effective treatments for patients suffering from chronic pain remain an area of intense focus within the pharmaceutical industry, as the development of novel therapies would help to treat an area of significant unmet medical need. The successful development of pharmacological agents to treat inflammatory and neuropathic pain conditions relies on a thorough understanding of the mechanisms that underlie the development and maintenance of chronic pain states. The goal of this review is to highlight recent discoveries regarding the intracellular signaling mechanisms that appear to play a critical role in persistent inflammatory and neuropathic pain. The review will focus on the mitogen activated protein kinase family of enzymes and the data suggesting that treatments designed to inhibit the activation of these enzymes may lead to significant advancements in the treatment of chronic pain. The review will also highlight the important interplay between neurons and non-neuronal cells (i.e., microglia and astrocytes) within the dorsal horn of the spinal cord in the generation and maintenance of chronic inflammatory and neuropathic pain. PMID- 22062047 TI - Molecular genotyping of Echinococcus granulosus in animal and human isolates from Egypt. AB - Despite, Egypt is started to be considered as an emerging endemic area for cystic echinococcosis (CE), no enough data in the literature about the exact status of the genotype in both animals and humans. Therefore, the present study aims to characterize the underlying genotypes that could be responsible for the transmission cycle and for the growing infectivity. Animal isolates were collected from 47 camels and 6 pigs. Human isolates are 31 CE cases including; 21 of hepatic cases, 5 of pulmonary cases and 5 multiple-organ affection cases. Hot Start specific PCR followed by DNA sequencing for mitochondrial 12S rRNA gene, revealed G1 genotype in one (3.2%) of 31 human isolate only. G6 genotype was detected in all the 53 (100%) animal isolates and in 30 out of 31 (96.8%) human isolate. The Egyptian G6 strain nucleotide sequence revealed 100% homology with an Argentinean reference strain 99% homology with the Kenyan G6 strain. It was concluded that G6 genotype is the predominant genotype in Egypt. PMID- 22062046 TI - The search for endogenous siRNAs in the mammalian brain. AB - A decade ago, RNA interference was proposed to serve as a physiologic means of regulating long-term gene expression in the mammalian brain. However, during the intervening years, this hypothesis appeared to be contradicted by both experimental data and theoretical considerations. More recently, the advent of deep sequencing technology has permitted a re-assessment of this issue. As reviewed here, a large population of small RNAs having features characteristic of endogenous siRNAs are detected within adult mouse hippocampus, which derive from genes involved in synaptic structure and signaling, and which show a significant, though modest (16-22%) up-regulation during olfactory discrimination training. Small RNAs derived from abundant cellular noncoding RNAs are also detected; in particular, a subpopulation of RNAs 25-30 nt. in length shows very large (>100 fold) up-regulation during olfactory discrimination training. Preliminary data suggest that the 25-30 nt. RNAs may associate with MIWI rather than Argonaute 1-4 homologues. I conclude that, despite their apparent low abundance, endogenous siRNAs and noncoding RNA-derived small RNAs are likely to play an important role in regulating synaptic plasticity. PMID- 22062048 TI - Biologically active polyamines in beef, pork and meat products: A review. AB - Dietary polyamines (PAs) putrescine (PUT), spermidine (SPD) and spermine (SPM) participate in an array of roles in human metabolism. Nevertheless, under some physiological conditions they can be undesirable. Meat and meat products are among important sources of PAs in human nutrition, mainly of SPM. The usual contents of PUT, SPD and SPM in fresh beef and pork are <2, <5 and 20-40mgkg(-1), respectively. Current information on changes of PAs during meat storage corresponds with PUT formation by bacterial activity mainly of pseudomonads and Enterobacteriaceae. However, data on SPD and SPM changes during meat chill storage have been inconsistent. Culinary processing of meat probably does not change SPD and SPM levels. PUT can be formed in different meat products in relation to the microbial population of the raw materials used and the hygienic level of manufacturing process. SPD and SPM contents seem to remain stable during processing of non-fermented meat products or decrease during dry-cured ham ripening. PUT contents increase commonly to 60-140mgkg(-1) in dry spontaneously fermented sausages, however, contents up to several hundreds mgkg(-1) are not extraordinary. Starter cultures are usually able to decrease PUT formation considerably. SPD and SPM contents in dry fermented sausages are comparable with levels typical for fresh meat. Data on SPD and SPM changes during ripening and storage are inconsistent. A decrease of the both polyamines during a storage period has been usually reported. PMID- 22062049 TI - Effect of low-temperature preservation on the quality of vacuum-packaged dry cured ham: Refrigerated boneless ham and frozen ham cuts. AB - The effect of storage on dry-cured ham quality was studied. Sixteen vacuum packaged boneless dry-cured hams and sixteen vacuum-packaged dry-cured ham cuts were stored in darkness under refrigeration (4+/-2 degrees C; 8 months) or freezing (-18+/-1 degrees C; 24 months), respectively. Instrumental colour and texture, physico-chemical and biochemical parameters, sensory profile and consumer acceptability and purchase satisfaction were measured throughout storage. The overall quality of refrigerated boneless dry-cured hams and frozen dry-cured ham cuts showed only limited changes throughout long-term storage. Significant changes involved loss of odour and flavour, increased adhesiveness and modification of hardness, the Semimembranosus muscle became tender while Biceps femoris became harder, leading to a higher textural homogeneity. In agreement with those changes, the overall acceptability assessed by a trained panel decreased throughout storage, though this was significant regarding only frozen hams. However, consumer evaluation of acceptability, as well as satisfaction with hypothetical purchasing, did not vary significantly throughout storage. PMID- 22062050 TI - The estimated accuracy of the EU reference dissection method for pig carcass classification. AB - This experiment was designed to describe the accuracy of the EU-reference dissection method, and to describe the types of factors influencing the accuracy and assess their size. The experiment was conducted in four different European countries at two abattoirs within each country. A total of 128 carcasses was selected according to carcass weight, fat class and sex, and 8 butchers from different countries dissected the carcasses. Due to the experimental design of the experiment a variation in pig type was found between countries. The accuracy was expressed by the repeatability and reproducibility standard deviation, which were found to be 0.87 and 1.10, respectively, and by the reliability, found to be 0.87. This indicates a high accuracy, although a significant effect was found on the estimation of lean meat percentage (LMP) of butcher, and also that jointing of the carcass was of overall importance to the accuracy of the EU-reference dissection method. PMID- 22062051 TI - Conjugated linoleic acid in meat and meat products: A review. AB - Conjugated linoleic acid (CLA) consists of a group of geometric and positional isomers of linoleic acid to which anticancerogenic, antidiabetic, and antiatherogenic effects, as well as effects on immune system, bone metabolism, and body composition are attributed. CLA is found predominantly in milk and meat of ruminants due to the importance of rumen micro-organism in the formation of CLA and its precursors. This review attempts to give an overview of the available data on intramuscular CLA concentrations in meat and meat products originating from different animal species. The factors influencing these concentrations are discussed and the estimated human daily intakes as well as the percentage provided by meat are reported. PMID- 22062052 TI - Association of MC4R gene variants with growth, fatness, carcass composition and meat and fat quality traits in heavy pigs. AB - The melanocortin receptor 4 (MC4R) gene is implicated in the regulation of feeding behaviour and body weight in humans and mice. A missense mutation (Asp298Asn) located in a highly conserved region of this gene has clearly been associated with backfat depth, feed intake and growth rate in different porcine lines. In this work the complete coding region of the gene was sequenced in samples from six pigs of a commercial hybrid line and two polymorphisms were detected at positions 709 (C/T) and 1426 (G/A). The last one corresponds to the missense mutation, and has been genotyped in 333 animals with phenotypic records and 68 out of their 81 parents. An association study of these genotypes with several performance and quality traits was performed within the statistical animal model framework. The results confirmed the effect of the missense mutation on growth and fat deposition traits (live weight at 140d and backfat depth), and supported new effects on carcass composition (loin and shoulder weights) and traits related to fat and meat quality (profile of fatty acids; muscle Minolta L(*), a(*) and H(o) colour parameters). A transmission-disequilibrium test provided no evidence of spurious association due to population stratification. PMID- 22062053 TI - Physical, chemical, and histological characteristics of 18 lamb muscles. AB - Muscles (n=18) were dissected from each side of 20 lamb carcasses to characterize physical, chemical, and histological traits. Muscles from the right sides were used to measure color values, expressible moisture, pH, total collagen content, and sarcomere length. Muscles from the left sides were aged for 7d and used to determine Warner-Bratzler shear (WBS) force values. The M. adductor and M. semimembranosus had the darkest colored lean (lowest L(*) values), whereas the M. latissimus dorsi and M. tensor fasciae latae had the lightest colored lean (highest L(*) values). The M. triceps brachii, M. pectoralis profundus, and M. latissimus dorsi had among the lowest numerical expressible moistures whereas the M. adductor and the M. longissimus lumborum had among the highest. The M. infraspinatus was found to have the highest collagen content (9.0mg/g) and the M. psoas major had the longest sarcomere length (3.1MUm). Of the muscles sampled, the M. serratus ventralis had one the lowest WBS values (21.8N) and the M. semimembranosus the highest (42.6N). On average, the largest muscles identified were the M. gluteobiceps, M. gluteus medius, M. longissimus lumborum, M. longissimus thoracis, and M. semimembranosus, which would likely be suitable in terms of physical dimensions for used in a variety of individual muscle applications. Other muscles, however, such as the M. teres major and M. tensor fasciae latae, may be too small in size and dimension to be used for individual application. PMID- 22062054 TI - Fatty acid composition of lambs of indigenous dairy Greek breeds of sheep as affected by post-weaning nutritional management and weight at slaughter. AB - The objective was to assess the effect of breed, sex, post-weaning nutrition and weight at slaughter on the fatty acids (FA) composition in carcass fat of lambs of indigenous Greek dairy breeds of sheep, the Boutsko (B), Serres (S) and Karagouniko (K) breed. The lambs (weaned at approximately 42 days) had been reared under different conditions of housing and feeding in three consecutive experiments (Experiment). In Experiment 1, lambs (n=120) were individually penned and fed ad libitum on a concentrate feed (11.3MJ metabolisable energy (ME)/kg DM and 192g crude protein (CP)/kg DM) together with 100g/day of Lucerne hay (8.3MJ ME/kg DM and 182g CP/kg DM). In Experiment 2, lambs (n=108) were fed the same concentrate on 3 different levels: High (H), Medium (M) and Low (L) and ad libitum on Lucerne hay. In Experiment 3, lambs (n=108) were initially group fed indoors for 63 days on 3 different levels of concentrate (H, M and L) together with ad libitum Lucerne hay. Thereafter they were finished on irrigated, sown pasture. Lambs were slaughtered at one of 5 standard proportions of mature weight (PMW) for each breed in Experiment 1 (i.e. 0.20, 0.30, 0.45, 0.60 and 0.90); at 3 fixed live weights in Experiment 2 (TSLW; i.e. 23, 28 and 33kg) and at 3 fixed PMW in Experiment 3 (PMW; i.e. 0.20, 0.48 and 0.54). The right hand side of their carcasses was minced and a random sample, around 200g, was taken. It was freeze dried and then grounded to obtain a quantity of 2g for lipid extraction and preparation of fatty acid methyl esters, which were assayed by gas-liquid chromatography to identify. Results were analysed separately for each experiment by analysis of variance. In Experiment 1, breed of lambs had significant effects (P<0.001) on C14:0, C16:0, C17:0, C18:2, C18:3 and C18:1 (P<0.05), whereas sex affected only the percentage of C15:0, C16:1 (P<0.001), C18:0 (P<0.01) and C18:2 (P<0.05). Live weight of lambs at slaughter had significant effects (P<0.05 0.001) on all the fatty acids. In Experiment 2, with the exception of C18:0 and C20:0, all other fatty acids were significantly affected by Breed (P<0.05-0.001). However, only C17:0, C18:0, C18:1 and C18:2 were significantly (P<0.001) affected by the level of concentrates in the diet. The major finding in Experiment 3 was the trend for saturated fatty acids to be lower; possibly due to the fact that lambs finished at pasture. It is concluded that there are possibilities of modifying FA composition in carcass fat of lambs by manipulation of post-weaning nutrition and slaughtering them at a wide range of live weights. PMID- 22062055 TI - Feeding Iberian pigs with acorns and grass in either free-range or confinement affects the carcass characteristics and fatty acids and tocopherols accumulation in Longissimus dorsi muscle and backfat. AB - The experiment was undertaken to provide information on the influence of grass intake in a high fat diet based on acorns, in either free-range or confinement, on the carcass yield and characteristics, and on the accumulation of fatty acids and tocopherols. Groups raised free-range or with acorns and grass in confinement had the highest total backfat. Grass addition to the feed did not significantly modify the carcass weight and cut yield. However, outdoor raising produced lower carcass weights and yield, Longissimus dorsi muscle and ham weights than those fed the formulated diet or acorns and grass in confinement. Neither grass intake nor outdoor rearing did modify significantly the proportion of saturated fatty acids of the backfat. However, a lower proportion of saturated fatty acids was found in the intramuscular neutral lipids from pigs fed outdoors. Pigs reared free-range had significantly (P=0.0001) higher proportions of C18:1n-9 in the inner layer and in the intramuscular neutral lipids than the other groups. The grass intake significantly (P=0.0001) increased the proportion of C18:3n-3 in the inner and outer fat layers and intramuscular neutral lipids, while the outdoor rearing system not only affected on the proportion of linolenic acid but also C22:5 and C22:6 of the inner backfat layer and intramuscular polar lipids. These results suggest that the outdoor rearing allows a higher accumulation of n-3 fatty acids maybe due to an increased activity of the desaturase and elongase enzymes. On the other hand, the accumulation of tocopherols was not significantly modified neither by the grass intake nor the outdoor rearing, while differences were detected by the type of feeding (diet vs. acorns/acorns and grass). It is concluded, that the outdoor rearing system affects the nutritional value of meat, mainly by improving the fatty acid composition. PMID- 22062056 TI - Inhibitory effect of organic acid salts on spoilage flora in culture medium and cured cooked meat products under commercial manufacturing conditions. AB - Lactobacillus curvatus, isolated from a spoiled vacuum-packaged 'pariza' type meat product, was used to inoculate modified MRS broth containing sodium lactate, sodium acetate and potassium sorbate in different concentrations, alone or in inter se combinations. Two commercial preparations (MIX 1 and MIX 2) were also used containing combinations of the above antimicrobials. Results from the preservatives addition to the culture medium showed highest antimicrobial activity in the case of the sodium lactate (2%, 3% or 4%), sodium acetate (0.5%) and potassium sorbate (0.15%) combination. Results from the preservatives addition to two types of thermally processed meats showed that sodium lactate and the combination of sodium lactate, sodium acetate and potassium sorbate were the most effective; extending the products shelf life an additional 10 days. Finally, MIX 1 and MIX 2 suppressed the lactic acid bacteria (LAB) growth in the culture medium but not in the final product. PMID- 22062057 TI - Carcass characteristics of suckling lambs protected by the PGI "Lechazo de Castilla y Leon" European quality label: Effect of breed, sex and carcass weight. AB - In the Region of "Castilla y Leon" (Spain), as in other Mediterranean areas, fresh suckling lamb meat is regarded as having a high edible quality. The EU granted this product a Protected Geographical Indication (PGI) "Lechazo de Castilla y Leon" in 1999. In this study, several carcass characteristics of suckling lambs protected by this PGI were determined, while the effects of breed, sex, and carcass weight were studied. Some differences in carcass characteristics within the three PGI authorized breeds have been detected. Neither carcass weight nor conformation measurements were good predictors of the composition of the PGI protected suckling lamb carcasses. The best predictors were fatness and composition of the leg and loin tissues, although dissection of these joints is not feasible on a daily basis. Lastly, some differences, due to sex and weight were identified in conformation, fat percentage, jointing and joint composition. Differences were, however, rather small, due to the lambs' young age and low variation in carcass weight. PMID- 22062058 TI - Potential probiotic Lactobacillus strains from fermented sausages: Further investigations on their probiotic properties. AB - A rational selection of probiotic microorganisms is an important challenge and requires the definition of fundamental information about the physiology and genetics of candidate strains. In this study, selected Lactobacillus (Lact.) strains already characterized in a previous study for their capability to resist low pH and to grow in conditions simulating the intestinal environment, were further investigated to explore their probiotic properties, such as the adhesion capability to intestinal human Caco-2 cell lines and their growth behaviour in the presence of various prebiotic carbohydrates. At first 25 Lactobacillus strains were characterized by pulsed field gel electrophoresis using the endonuclease NotI. Among them, 13 strains belonging to the Lact. plantarum-group were identified at species level by a multiplex PCR assay. Subsequently 11 Lactobacillus strains showing different PFGE restriction pattern and the best acid- and bile-resistances, were chosen to investigate their in vitro adhesion capability to human intestinal epithelial cells and their fermentation properties of five prebiotic substances (FOS, Inulin, IMO, GOS and lactulose) at a concentration of 2%. The 11 strains analysed in this study possessed good adhesion capability to Caco-2 cell layers and, in particular, the eight strains belonging to the Lact. plantarum-group showed the higher final number of viable adhering cells. Moreover a species-related fermentative behaviour was pointed out and the strain Lact. paracasei EL7 was the only one able to grow in the presence of all prebiotics tested. In conclusion the strains of Lactobacillus studied in this research could be further investigated to assess possible in vivo human health benefits. PMID- 22062059 TI - Effect of weaning status and storage time under vacuum upon physical characteristics of meat of the Rubia Gallega breed. AB - Seven to nine months old calves are the typical production of Rubia Gallega, which is the most important beef breed in Spain. A study about the influence of weaning status and vacuum storage time on veal quality characteristics is needed. The muscle longissimus thoracis from 22 non-weaned (NW) and 21 weaned (W) calves at 1day post-slaughter, and vacuum packaged for 7 and 14 days were analysed. NW showed higher yellowness and hue values than W but lower pigment concentration. The differences disappeared at longer storage times. The redness, yellowness, hue and chroma increased with aging, but the pigment concentration, expressible juice and toughness decreased with aging. Principal component analysis showed that colour variables were the most determinant characteristics in quality variation. The canonical discriminant analysis separated the samples in three groups: 1 day post-slaughter W, 1day post-slaughter NW, and vacuum packaged W and NW. PMID- 22062060 TI - Using machine learning procedures to ascertain the influence of beef carcass profiles on carcass conformation scores. AB - In this study, a total of 163 young-bull carcasses belonging to seven Spanish native beef cattle breeds showing substantial carcass variation were photographed in order to obtain digital assessments of carcass dimensions and profiles. This dataset was then analysed using machine learning (ML) methodologies to ascertain the influence of carcass profiles on the grade obtained using the SEUROP system. To achieve this goal, carcasses were obtained using the same standard feeding regime and classified homogeneous conditions in order to avoid non-linear behaviour in grading performance. Carcass weight affects grading to a large extent and the classification error obtained when this attribute was included in the training sets was consistently lower than when it was not. However, carcass profile information was considered non-relevant by the ML algorithm in earlier stages of the analysis. Furthermore, when carcass weight was taken into account, the ML algorithm used only easy-to-measure attributes to clone the classifiers decisions. Here we confirm the possibility of designing a more objective and easy to-interpret system to classify the most common types of carcass in the territory of the EU using only a few single attributes that are easily obtained in an industrial environment. PMID- 22062061 TI - Retail cutting characteristics for US Choice and US Select beef subprimals. AB - US Choice (Ch) and US Select (Se) beef subprimals from the rib, chuck, plate, loin, and round were obtained to conduct retail cutting tests. Subprimals were merchandised into bone-in or boneless retail cuts and associated components by experienced retail meat merchandisers. These Se subprimals had less (P<0.05) trimmable fat than their Ch counterparts: ball tip, top sirloin, outside round, inside round, and ribeye. Se inside rounds, outside rounds, eye of rounds, boneless striploins, and ball tips had greater (P<0.05) purge losses than the same cuts from Ch. The only subprimals where grade impacted total saleable yield were the top (inside) rounds (Ch=80.13%, Se=87.34%; P=0.004) and outside rounds cut into roasts, steaks, and cubed steaks (Ch=87.61%, Se=90.28%; P=0.05). Methods to increase retail yields from beef subprimals should consider minimizing purge and increasing cutting efficiencies in addition to reducing fat trim. PMID- 22062062 TI - An assessment of dietary supplementation with tea catechins and rosemary extract on the quality of fresh beef. AB - The effect of supplementation of beef cattle diets with tea catechins (TC) (1000mg/animal/day) and rosemary extract (RE) (1000mg/animal/day), for 103 days preceding slaughter, on the oxidative stability of M. longissimus dorsi (LD) steaks was evaluated. Dietary supplementation with TC and RE did not increase plasma total antioxidant status (TAS), LD alpha-tocopherol concentrations or pH. In LD steaks stored aerobically or in modified atmosphere packs (80% O(2):20% CO(2)) (MAP) for up to 8 days at 4 degrees C, surface redness (CIE 'a' redness value) and lipid stability (TBARS, mg MDA (malondialdehyde)/kg muscle) were not significantly improved as a result of supplementation with TC and RE. Similarly no improvement in the sensory properties and lipid stability of cooked LD slices, stored aerobically or in 30% CO(2):70% N(2) for up to 11 days at 4 degrees C, was observed. An in vitro fermentation study demonstrated that TC and RE were not fermented to any great extent under simulated rumen conditions. Direct addition of TC (1000ppm) and RE (1000ppm) significantly (P<0.05) improved the colour and lipid stability in LD patties stored in 80% O(2):20% CO(2) for up to 8 days at 4 degrees C, thus, demonstrating the antioxidant potential of TC and RE supplements employed in the present study. PMID- 22062063 TI - Allelic incidence in several pig breeds of a missense variant of pig melanocortin 4 receptor (MC4R) gene associated with carcass and productive traits; its relation to IGF2 genotype. AB - MC4R, melanocortin-4 receptor, is involved in feed intake regulation. A mutation in a single base of MC4R, a G/A substitution in position 1426, has been linked to enhanced backfat thickness, average daily gain and daily feed intake. We present in this work a method to diagnose this mutation using real time PCR (RT-PCR) which allows rapid, cheap and reliable analysis of hundreds of samples in just 2h after DNA extraction. We have used this RT-PCR based assay to study the incidence of the mutation in several pig breeds or crosses (Iberian, Duroc, Pietrain, Large White, Large White*Pietrain) and wild boars. IGF2, insuline like growth factor 2, a gene with well demonstrated effects on carcass composition, of all these animals has also been analyzed and we show, using linkage disequilibrium analysis that both genes are independent. The implications of our results for pig selection toward fatty or lean carcasses are discussed. PMID- 22062064 TI - Manipulation of the pre-rigor glycolytic behaviour of bovine M. longissimus dorsi in order to identify causes of inconsistencies in tenderness. AB - The aim of this study was to monitor the effects of the alteration of the pre rigor environment of the bovine LD muscle using controlled temperature regimes in order to gain an insight into the early post-mortem pH/temperature/time interactions which are important from the point of view of tenderness and to identify possible reasons for inconsistencies in beef tenderness. LD muscles (n=12) were hot-boned within 90min post-slaughter, cut into three pieces which were randomly placed in polyethylene bags and submerged in water baths pre-set at the following temperatures; 0, 5, 10, 15, 20 and 25 degrees C for 8 h post-mortem then stored at 2 degrees C for up to 14-days post-mortem. The rate of pH decline increased with increasing temperature. Muscles incubated at 0 and 5 degrees C were cold shortened however not all of these muscles were tough as indicated by Warner Bratzler shear force values (WBSF). A pH range of 5.9-6.2 at 3 h post mortem (pH(3)) produced consistently tender beef where cold-shortening was avoided. Cold shortened muscles showed the greatest variation in tenderness at 14 days post-mortem and underwent the greatest amount of tenderisation (DeltaWBSF) and proteolysis between days 2 and 14 post-mortem. Proteolysis of cold shortened muscle may induce variation in tenderness in these muscles. PMID- 22062065 TI - Influence of dietary oils and protein level on pork quality. 1. Effects on muscle fatty acid composition, carcass, meat and eating quality. AB - This study evaluated the effects of three dietary oils - palm kernel (PKO), palm (PO) and soyabean (SBO) - and two protein levels - high (HP) and low (LP) in a 3*2 factorial design involving 60 pigs on growth performance, muscle fatty acid composition and content, carcass, meat and eating qualities. Oil type did not have a significant effect on growth and carcass quality. PKO significantly reduced the polyunsaturated (PUFA) to saturated (SFA) fatty acid (P:S) ratio in longissimus muscle (P<0.001). PKO increased the concentrations of lauric (12:0), myristic (14:0), palmitic (16:0) and stearic (18:0) fatty acids and decreased linoleic acid (18:2). The LP diet increased intramuscular fat (IMF) from 1.7g/100g muscle in HP to 2.9g/100g (P<0.001), increased tenderness by 0.6 units (P<0.01) and juiciness by 0.5 units (P<0.01) on the 1-8 scale, but at the expense of lower daily weight gain (P<0.01), lower feed conversion efficiency (P<0.01), reduced P:S ratio (P<0.001) and increased lipid oxidation (P<0.01). The results suggest that PKO and PO could be used in tropical developing countries as cheaper alternatives to SBO for the production of good quality and healthy pork, but their limits of inclusion need to be determined. PMID- 22062066 TI - Influence of dietary oils and protein level on pork quality. 2. Effects on properties of fat and processing characteristics of bacon and frankfurter-style sausages. AB - Palm kernel oil (PKO) and palm oil (PO) are used in tropical countries as cheaper substitutes for conventional feed sources such as soya bean oil (SBO) but little is known about their effects on meat quality. This study, therefore, evaluated the effects of these three dietary oils on the fatty acid composition (FA) of pork fat and the qualities of belly bacon and frankfurter sausage. The 3*2 factorial design also included high and low dietary protein. Total cooking loss, water loss and fat losses were determined in frankfurter sausages at chopping temperatures from 2 to 24 degrees C. PKO resulted in a poor P:S ratio (0.34) and a relatively hard fat (slip point 32.8 degrees C), but resulted in bacon with a higher tensile cohesive force and more high quality slices, judged subjectively. PO had a fatty acid composition closer to the SBO control, a better P:S ratio than PKO (0.48) and softer fat. There was a trend for total cooking losses and fat losses to be higher in PKO compared with PO and SBO at all chopping temperatures, suggesting that the firmest, most saturated fat (PKO) was least suitable for frankfurter production. The low protein diet increased the concentration of saturated fatty acids and increased fat firmness but its effect on fatty acid composition and other properties were less marked than those of oil type. PMID- 22062067 TI - Behaviour of the constitutive biota of two types of Spanish dry-sausages ripened in a pilot-scale chamber. AB - The behaviour of the constitutive biota in eighty four samples belonging to two different types of Spanish dry-cured sausages during the ripening process in a pilot-scale chamber was investigated. Samples were analyzed in three stages during production: fresh product, first drying stage and finished product. Lactic acid bacteria (LAB) and Coagulase-negative cocci (CNC) were identified by the API system. In general, evolution of LAB and CNC during the ripening process of Spanish dry-cured sausages increased during the first days after which numbers of these organisms remained stable. Pediococcus pentosaceus and Staphylococcus xylosus, were the dominant species. Lactobacillus plantarum, Staphylococcus saprophyticus Staphylococcus simulans and Kocuria varians were also present. The results obtained show that the ripening process in a pilot-scale chamber under controlled conditions contributes to a more homogeneous behaviour of the constitutive biota, in comparison with commercial production standards. PMID- 22062068 TI - Prediction of pork quality using visible/near-infrared reflectance spectroscopy. AB - Near-infrared spectroscopy is a rapid screening technique that may be used to determine meat quality traits. While several calibrations on meat quality parameters have been published, the accuracy and robustness of a calibration has rarely been validated with independent samples. In this study, in 207 loin muscles from three independent batches of pigs of different breeds drip loss, colour values, pH and intramuscular fat were determined. Calibrations were made from each combination of two batches and validated with the third batch. Validations of pH, intramuscular fat, drip loss, and L(*), a(*), and b(*) colour values had on average 1.27 times the accuracy of the calibration. Breed did not influence the accuracy of the calibration. Intramuscular fat can be determined with good accuracy. Muscle pH and colour values are reasonably well predicted. Drip loss can not be determined quantitatively with sufficient accuracy, but classification of quality groups is possible. PMID- 22062069 TI - Paper by Zamora et al. (2005), Serine peptidase inhibitors, the best predictor of beef ageing amongst a large set of quantitative variables, Meat Science, 71, 730 742. PMID- 22062070 TI - Zamora et al. (2005). Serine peptidase inhibitors, the best predictor of beef ageing amongst a large set of quantitative variables, Meat Science, 71, 730-742. PMID- 22062071 TI - Effect of nisin and its combination with sodium chloride on the survival of Listeria monocytogenes added to raw buffalo meat mince. AB - Antilisterial activity of nisin (Nisaplin), alone at concentrations of 400 and 800 IU/g and in combination with 2% sodium chloride was incorporated in raw buffalo meat mince. Samples of the raw meat mince were inoculated with 10(3) colony forming units (cfu)/g of L. monocytogenes and stored at 4 degrees C for 16 days and at 37 degrees C for 36 h. Initial estimates of pH, extract release volume, mesophilic and psychrophilic counts were found to be 5.74, 48 ml, 3.5*10(5) and 1.0*10(5) cfu/g of meat, respectively. The growth of L. monocytogenes in the treated groups was significantly (P<0.05) inhibited compared to the control group. The degree of inhibition increased with increasing concentration of nisin and decreasing storage temperature. Addition of 2% sodium chloride in combination with nisin increased the efficacy of nisin at both storage temperatures. The pH in the treated groups remained significantly lower (P<0.01) than in the control groups at both 4 and 37 degrees C. PMID- 22062072 TI - Warmed-over flavour analysis in low temperature-long time processed meat by an "electronic nose". AB - The ability of an electronic nose, comprising 32 conducting polymer sensors, to identify and classify warmed-over flavour (WOF) aroma in bovine semitendinosus muscle, processed by vacuum cook-in-bag/tray technology (VCT) and storage under refrigerated conditions, was evaluated. The VCT process employed low temperature long time (50 degrees C-390 min) thermal treatments. Multivariate analysis showed that VCT processed beef aroma profiles were sorted into two groups, one included samples stored for up to 20 days and the other included samples with 34 to 45 days of storage. WOF odour standard samples were recognised to have similar aroma as samples of the second group. Lipid oxidation results, measured by thiobarbituric acid reactive substances, showed an increment in oxidation level for samples stored for 34 days or more (P<0.05). This study shows that electronic nose technology can be applied to WOF odour identification and classification in VCT beef meat, complementing chemical and sensory techniques used in this field. PMID- 22062073 TI - Effects of growth-promoting implants on morphology of Longissimus and Semitendinosus muscles in finishing steers. AB - Growth-promoting implants lead to increased muscle accretion in ruminants. To elucidate the effects at a cellular level, muscle fiber distribution and cross sectional area (CSA) of longissimus (LM) and semitendinosus (ST) muscles were compared in implanted and control steers. Sixty-four Charolais steers were assigned to one of four treatments (16 steers/treatment): (1) no implant, (2) Synovex-S(r) (estradiol benzoate+progesterone), (3) Ralgro(r) (zeranol) or (4) Revalor-S(r) (trenbolone acetate+estradiol-17beta). The experiment was carried out using four slaughter groups (SGRP). Sixteen steers each were slaughtered after 48, 104, 160 and 175 days (four steers/treatment) on trial. Steers on an implant treatment were first implanted at 15 months of age (day 0) and re implanted at 56 and 112 days. Muscle fibers in the LM and ST (for both live biopsy and post-mortem samples) were characterized as either slow-twitch oxidative (SO), fast-twitch oxidative-glycolytic (FOG) and fast-twitch glycolytic (FG) fibers. Fiber distribution was minimally affected by SGRP in these physiologically mature steers. Implantation with Synovex did not alter fiber distribution in either muscle compared with control steers. Both Synovex implanted and control steers showed a decrease of FG and an increase of FOG fibers in the LM from day 0 to SGRP 2 followed by an increase of FG and a decrease of FOG fibers. Ralgro- and Revalor-implanted steers had an almost constant fiber distribution in the LM throughout the experiment resulting in higher precentages of FG fibers in SGRP 2 (P<0.05) than SYN or CON steers. Biopsy samples of the LM muscle which were excised 51 days (SGRP 1-3) or 65 days (SGRP 4) before slaughter proved to be suitable for the determination of fiber distribution in live animals. Fiber area increased in post-mortem samples of both muscles from SGRP 1-3 in all treatment groups followed by a plateau. Implantation with Revalor led to an additional increase in fiber area from SGRP 3 and 4 (P<0.05). Synovex did not affect fiber area compared with control steers whereas Ralgro and Revalor implants led to larger fibers in SGRP 3 and 4, respectively. It can be concluded that some growth-promoting implants result in noticeable differences in muscle hypertrophic responses which coincide with their different effectiveness to enhance lean mass accretion. PMID- 22062074 TI - Changes in lysosomal enzyme activities and shear values of high pressure treated meat during ageing. AB - The effects of pressure treatment (520 MPa for 260 s at 10 degrees C) on lysosomal enzyme activities, Warner-Bratzler (WB) shear values and physico chemical parameters of post-rigor (day 2) beef (Biceps femoris and Longissimus dorsi muscles) were investigated immediately after treatment and during ageing. Activities of cathepsin D and acid phosphatase in pressurised meat samples were higher than in controls at 2 days post-mortem and throughout storage. This increase in activities was related to the breakdown of the lysosomal membrane and/or to enzyme activation. The WB peak forces were higher for pressurised samples of both muscles at 2 days than in the control and remained higher throughout ageing. The WB shear force deformation curves from pressurised samples showed that the increase in toughness was due to the increase in shear force of the myofibrillar component and not the collagen component. Pressurised muscle led to a significant decrease in sarcomere length and higher cooking loss. Post-rigor application of high pressure induced higher catheptic activity but no conclusive effect on the post-mortem rate of tenderization or tenderness of meat was observed. PMID- 22062075 TI - Purification and characterization of a soluble methionyl aminopeptidase from porcine skeletal muscle. AB - A soluble aminopeptidase was purified from porcine skeletal muscle by ammonium sulfate fractionation and two successive anion exchange chromatographic procedures. The enzyme eluted at 0.17 M NaCl, had a relative molecular mass of 53 KDa (by SDS-polyacrylamide gel electrophoresis) and was activated by sulfydryl compounds. Activity was optimal at pH 7.5 and 40 degrees C and showed broad aminopeptidase and low endopeptidase activities. The aminopeptidase exhibited maximal activity against Met-, Lys-, Ala-, and Leu-7-amido-4-methyl-coumarin ( AMC), while Pro-AMC was not hydrolyzed. Inhibition of enzyme activity was observed in the presence of sulfydryl reagents, iodoacetic acid, puromycin, leupeptin and amastatin, but it was not affected by serin and aspartic protease inhibitors, EDTA and bestatin. The enzyme activity was not inhibited by sodium chloride and, therefore, the enzyme has potential for contributing to the generation of free amino acids in cured pork meat products. PMID- 22062076 TI - The use of principal component analysis (PCA) to characterize beef. AB - Principal component analysis was performed to study the relationships between chemical, physical and sensory variables (n=18) measured on longissimus thoracis et lumborum of 79 young bulls from the following ethnic groups: hypertrophied Piemontese, normal Piemontese, Friesian, crossbred hypertrophied Piemontese*Friesian, Belgian Blue and White. The first three PCs explained about 63% of total variability. Sensory characteristics, protein content, shear force and cooking losses resulted the most effective variables for the PC1, while hydroxyproline and ether extract content, as well as hue and lightness were useful to define the PC2. The distribution of the objects on the axes of the first two PCs allowed the identification of two groups, the first one including meats of the hypertrophied animals (Piemontese and Belgian Blue and White) the second one including normal Piemontese and Friesian. However, a considerable variability within groups was noted. The crossbreds were placed between the two previous groups. In conclusion, PCA proved to be a very effective procedure to obtain a synthetic judgement of meat quality. PMID- 22062077 TI - Quantification of myosin heavy chain isoform in porcine muscle using an enzyme linked immunosorbent assay. AB - The objective of this study was to develop an indirect enzyme-linked immunosorbent assay (ELISA) to quantify the relative abundance of the myosin heavy chain (MyHC) isoforms in porcine muscle. Longissimus muscle samples were taken from halothane positive (HAL+) and negative (HAL-) pigs and subjected to ELISA using newly generated and commercially available myosin monclonal antibodies (mAbs). Muscle of HAL+ pigs possessed less type I (P <0.01) and IIA (P<0.1), and more type IIB MyHC (P <0.01) than muscle of HAL- pigs. Abundance of IIX MyHC content was negatively correlated (P < 0.0001) to the amount of IIB MyHC in porcine muscle. These data show indirect ELISA can be used to detect genotype differences in muscle MyHC content, and it provides a rapid, sensitive method for determining muscle fiber type in porcine skeletal muscle. Furthermore, these data suggest that the proportion of glycolytic muscle fibers increases at the expense of oxidative fibers. PMID- 22062078 TI - Effect of rapid and conventional cooling methods on the quality of cooked ham joints. AB - Three cooling regimes, vacuum (VC), blast (BC) and slow cooling (SC), were compared for their effect on cooling rate, weight loss and quality of large cooked ham joints. Vacuum cooling reduced the cooling rate (70-4 degrees C) significantly (P<0.05) in comparison to the other methods; mean cooling times for cooked hams (5-6 kg) were 1.9 h for VC, 11.7 for BC and 14.3 for SC. However, VC gave an increased chill loss (P<0.05) of ca. 11% compared to ca. 4% for the other methods due to evaporative moisture loss. Sensory panels found that VC hams were tougher and less juicy (P<0.05). Shear force measurements and texture profile analysis also showed the vacuum cooling to have a toughening effect on the cooked ham. While vacuum cooling had an adverse effect on quality and yield, it was the only one that conformed to recent safety guidelines for cooked meat joints of a reduction in temperature to 5 degrees C inside 10 h. The cooling conditions used do not reproduce full-scale industrial practice, however, the effects found serve as an indicator of the potential benefits and drawbacks of vacuum cooling for cooked meat joints. PMID- 22062079 TI - The influence of elevated temperature conditioning on bison (Bison bison bison) meat quality. AB - Elevated temperature conditioning (ETC: 10 degrees C until 10 h post mortem) was effectively employed as a means of cooling bison carcasses in order to avoid the cold-induced meat quality defects that are a risk with conventional bison carcass chilling (0-2 degrees C for 24 h). The ETC treatment maintained internal M. Longissimus lumborum and M. Semimembranosus temperature above 10 degrees C within the first 10 h post mortem. The time/temperature combination did not result in significant evaporative loss, although loss of weight during carcass cooling can represent a practical economic loss. ETC accelerated post-mortem glycolysis and pH decline, and resulted in samples of lighter, more intense red colour than those conventionally chilled. Significant improvement in both initial tenderness and tenderization during ageing was realized with the use of ETC. PMID- 22062080 TI - Dietary tea catechins and iron-induced lipid oxidation in chicken meat, liver and heart. AB - The effects of dietary tea catechins (TC) supplementation at levels of 50 (TC 50), 100 (TC 100), 200 (TC 200), and 300 (TC 300) mg kg(-1) feed on susceptibility of chicken breast meat, thigh meat, liver and heart to iron induced lipid oxidation were investigated. Day old chicks (n=200) were randomly divided into six groups. Chicks were fed diets containing either basal (C), or alpha-tocopheryl acetate supplementation at a level of 200 mg kg(-1) feed (VE 200), or TC supplementation for 6 weeks prior to slaughter. Lipid oxidation was assessed by monitoring malondialdehyde formation with 2-thiobarbituric acid (TBA) assay. TC supplementation at all levels exerted antioxidative effects for all tissues with the exception of 50 mg kg(-1) feed for breast meat. TC supplementation at levels of 200 and 300 mg kg(-1) feed were found to be significantly (P<0.05) more effective in retarding lipid oxidation in all tissues, compared to the control. TC supplementation at a level of 300 mg kg(-1) feed was also found to be significantly (P<0.05) superior to vitamin E supplementation at a level of 200 mg kg(-1) feed (VE 200) for oxidative stability in chicken thigh meat, but it was inferior to VE 200 in chicken liver and heart. TC supplementation at a level of 50 mg kg(-1) feed was found to be pro-oxidative in breast meat, but this did not occur in chicken thigh meat, liver and heart. The variation of TC antioxidative properties in different tissues may be explained by the uneven distribution of lipid, iron and TC accumulation in tissues. PMID- 22062081 TI - Halothane genotype, pre-slaughter handling and stunning method all influence pork quality. AB - Seventy-six Landrace and four Large White * Landrace pigs (n=80) of 90-134 kg liveweight were randomly allocated to a 2*2*2 factorial experiment to determine the effect of halothane genotype [heterozygous for the halothane gene (Nn) and homozygous dominant (NN)], pre-slaughter handling (minimal and negative) and stunning method (CO(2) stunning and electrical) on pork quality. The rate of muscle pH decline post-slaughter of the m. longissimus thoracis et lumborum (LTL) muscle was faster in Nn pigs compared with NN pigs (0.86 and 0.30 pH units/h, respectively). Pork from Nn pigs was also paler in colour, had higher percentage drip loss and purge and lower sarcoplasmic and myofibrillar protein solubility compared with NN pigs. Pork from CO(2) stunned pigs had a lower drip loss compared to pork from electrically stunned pigs (5.80 and 7.28%, respectively - means of both genotypes combined). Tenderness of pork assessed at 24 h post slaughter was not influenced by genotype, pre-slaughter handling or stunning method. However, pork from Nn pigs aged for 5 days post-slaughter was less tender than NN pigs (5.84 and 4.84 kg, respectively). Pale, soft and exudative pork was produced in all negatively handled Nn pigs, regardless of stunning method. The average amount of ecchymosis-affected muscle trimmed from carcasses of electrically stunned pigs was higher compared to pigs stunned with CO(2) (65 and 0.7 g, respectively). These data indicate that although halothane status was the most important factor influencing pork quality, pre-slaughter handling and stunning method also influenced meat and carcass quality. PMID- 22062082 TI - Effect of ion fluid injection on beef tenderness in association with calpain activity. AB - Sodium pyrophosphate plus sodium chloride (PPi) was injected into pre-rigor, hot boned biceps femoris (BF) and semimembranosus (SM) muscle from 12 heifer carcasses. The PPi injection caused higher pH values between 10 and 48 h post mortem than found in the controls for both muscles (P<0.05). PPi injection resulted in faster decreases in the activities of MU-calpain and calpastatin than in the control for both muscles with time post-mortem (P<0.05). There were significant differences between treatments in both the BF and SM (P<0.05). There was evidence that PPi-injection elevated pH, and accelerated activation of calpains, resulting in improved tenderness. The rates of degradation of titin and troponin-T as well as the appearance of 95 and 30 kDa peptides were faster in the PPi-injected muscles than the controls. PPi-injection elevated muscle pH, which was attributed to acceleration of the calpain activation. It is concluded that PPi-injection improved beef tenderness by accelerating activation of calpain. PMID- 22062083 TI - Meat tenderization by proteolytic enzymes after osmotic dehydration. AB - The treatment of proteolytic enzymes is one of the popular methods for meat tenderization. In this case, it is very important how to introduce the enzymes into the meat cut. This paper describes meat tenderization by dipping the meat cut in a solution containing proteolytic enzymes after contact-osmotic dehydration. After the dehydration of each piece of meat from culled cow for 18 h by contact-dehydration sheet, each sample was dipped for 3 h in a solution containing papain or proteinases from Aspergillus traditionally used for soysauce production in Japan. It was stored at 3~4 degrees C for 24, 48 and 168 h, and subjected to texture measurement, sensory evaluations, biochemical analysis and histological observations. The penetration efficiency of the enzyme solution (of around 80%) after the contact-osmotic dehydration seemed to be sufficient. A marked decrease in hardness by texture measurements was observed in the meats treated with proteolytic enzymes and higher sensory scores for tenderness were observed in the meats treated with enzymes as compared with the untreated meat. The papain-treated meat received the highest score in tenderness, but the scores given to juiciness and taste were lower than that of the control. The rapid increases of the fragmentation of myofibrils from the enzyme-treated meat were observed at first 24 h of storage as compared with that of the control. Remarkable degradation of myosin molecule in the myofibrils from the enzyme treated meats was observed on SDS-PAGE profiles. Considerable degradation of myofibrilar structure especially due to proteolytic removal of Z-lines, was observed among the myofibrils from enzyme-treated meats by electronmicroscopy. The remarkable deformation and disruption of honeycomb-like structure of endomysium were also observed in the meats treated with enzymes. From these results, it was shown that treatment after osmotic dehydration, was effective in tenderizing. PMID- 22062084 TI - Meat Science: An Introductory Text. P.D. Warriss (L25, US $ 45). CABI Publishing. PMID- 22062085 TI - Combination treatment with pioglitazone and fenofibrate attenuates pioglitazone mediated acceleration of bone loss in ovariectomized rats. AB - Peroxisome proliferator-activated receptor (PPAR) gamma agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARalpha agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ~50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (~45%) and bone mineral density (BMD; ~60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARgamma and PPARalpha may reduce the negative effects of PPARgamma agonism on bone mass. PMID- 22062086 TI - Rapid detection by multiplex PCR of Genomic Islands, prophages and Integrative Conjugative Elements in V. cholerae 7th pandemic variants. AB - Vibrio cholerae poses a threat to human health, and new epidemic variants have been reported so far. Seventh pandemic V. cholerae strains are characterized by highly related genomic sequences but can be discriminated by a large set of Genomic Islands, phages and Integrative Conjugative Elements. Classical serotyping and biotyping methods do not easily discriminate among new variants arising worldwide, therefore the establishment of new methods for their identification is required. We developed a multiplex PCR assay for the rapid detection of the major 7th pandemic variants of V. cholerae O1 and O139. Three specific genomic islands (GI-12, GI-14 and GI-15), two phages (Kappa and TLC), Vibrio Seventh Pandemic Island 2 (VSP-II), and the ICEs of the SXT/R391 family were selected as targets of our multiplex PCR based on a comparative genomic approach. The optimization and specificity of the multiplex PCR was assessed on 5 V. cholerae 7th pandemic reference strains, and other 34 V. cholerae strains from various epidemic events were analyzed to validate the reliability of our method. This assay had sufficient specificity to identify twelve different V. cholerae genetic profiles, and therefore has the potential to be used as a rapid screening method. PMID- 22062087 TI - Kinetic anomalies in the interactions of Nile red with microalgae. AB - Nile red (NR) is a popular fluorescent indicator to visualize lipid bodies in intact cells and has been extensively utilized to monitor triglyceride accumulation in microalgae. Typically, addition of NR to algae results in a rapid fluorescence enhancement followed by fluorescence quenching. NR fluorescence rise can be resolved into two kinetic phases: a fast phase (P1, sec), monitored at 525 nm/630 nm, followed by a slower phase (P2, min), monitored at 488 nm/575 nm. Studies with isolated plasma membrane (PM) and lipid globule (LG) preparations, suggest that P1 and P2 represent entry to the PM and transfer to LG, respectively. High NaCl slows down the interactions of NR with algae and with lipid globules. The onset of NR fluorescence quenching varies in different algae species between 5 min to 1h, and is observed in intact cells and in isolated LG. NR fluorescence quenching depends on NR concentration and is almost eliminated at low NR/cell ratios, indicating that it results from self-interactions of LG associated dye. Glycerol has a dual effect on NR fluorescence: it eliminates kinetic anomalies resulting from limited solubility and self-interactions, but it also quenches NR fluorescence. NR fluorescence quenching by glycerol, as well as NR fluorescence enhancement by iodide anions, was observed only at high NR/LG ratios. These findings suggest that lipid-associated NR is more exposed to hydrophilic quenchers at high than at low NR concentrations. The results emphasize the importance of defining the optimal time window and NR concentrations for monitoring lipid accumulation in microalgae by NR fluorescence and clarify the origin of spectral anomalies resulting from self-interactions of dye molecules. PMID- 22062088 TI - MALDI-typing of infectious algae of the genus Prototheca using SOM portraits. AB - BACKGROUND: MALDI-typing has become a frequently used approach for the identification of microorganisms and recently also of invertebrates. Similarity comparisons are usually based on single-spectral data. We apply self-organizing maps (SOM) to portray the MS-spectral data with individual resolution and to improve the typing of Prototheca algae by using meta-spectra representing prototypes of groups of similar-behaving single spectra. RESULTS: The MALDI-TOF peaklists of more than 300 algae extracts referring to five Prototheca species were transformed into colored mosaic images serving as molecular portraits of the individual samples. The portraits visualize the algae-specific distribution of high- and low-amplitude peaks in two dimensions. Species-specific pattern of MS intensities were readily discernable in terms of unique single spots of high amplitude MS-peaks which collect characteristic fingerprint spectra. The spot patterns allow the visual identification of groups of samples referring to different species, genotypes or isolates. The use of meta-peaks instead of single peaks reduces the dimension of the data and leads to an increased discriminating power in downstream analysis. CONCLUSIONS: We expect that our SOM portray method improves MS-based classifications and feature selection in upcoming applications of MALDI-typing based species identifications especially of closely related species. PMID- 22062089 TI - Symposium on meat safety: From abattoir to consumer. PMID- 22062090 TI - Challenges to meat safety in the 21st century. AB - The safety of meat has been at the forefront of societal concerns in recent years, and indications exist that challenges to meat safety will continue in the future. Major meat safety issues and related challenges include the need to control traditional as well as "new," "emerging," or "evolving" pathogenic microorganisms, which may be of increased virulence and low infectious doses, or of resistance to antibiotics or food related stresses. Other microbial pathogen related concerns include cross-contamination of other foods and water with enteric pathogens of animal origin, meat animal manure treatment and disposal issues, foodborne illness surveillance and food attribution activities, and potential use of food safety programs at the farm. Other issues and challenges include food additives and chemical residues, animal identification and traceability issues, the safety and quality of organic and natural products, the need for and development of improved and rapid testing and pathogen detection methodologies for laboratory and field use, regulatory and inspection harmonization issues at the national and international level, determination of responsibilities for zoonotic diseases between animal health and regulatory public health agencies, establishment of risk assessment based food safety objectives, and complete and routine implementation of HACCP at the production and processing level on the basis of food handler training and consumer education. Viral pathogens will continue to be of concern at food service, bacterial pathogens such as Escherichia coli O157:H7, Salmonella and Campylobacter will continue affecting the safety of raw meat and poultry, while Listeria monocytogenes will be of concern in ready-to-eat processed products. These challenges become more important due to changes in animal production, product processing and distribution; increased international trade; changing consumer needs and increased preference for minimally processed products; increased worldwide meat consumption; higher numbers of consumers at-risk for infection; and, increased interest, awareness and scrutiny by consumers, news media, and consumer activist groups. Issues such as bovine sponginform encephalopathy will continue to be of interest mostly as a target for eradication, while viral agents affecting food animals, such as avian influenza, will always need attention for prevention or containment. PMID- 22062091 TI - Microbial safety of meat in the European Union. AB - The two most frequently reported zoonotic diseases in humans in the EU in 2005 were Campylobacter and Salmonella infections with incidences of 51.6 and 38.2 cases per 100,000 population, respectively. Reported human infections caused by Yersinia spp., Verocytotoxigenic Escherichia coli, and Listeria monocytogenes had comparably lower incidences of 2.6, 1.2 and 0.3 cases per 100,000 population, respectively. Meat and meat products are important sources for these infections but knowledge on exactly how important they are compared with other types of food, drinking water and environmental exposure is quite limited. Occurrences of zoonotic pathogens in raw meat are variable, although most often are between 1% and 10%, depending on the organism, geographical factors, farming and/or meat production practices, etc. Zoonotic pathogens in meat have to be controlled through a complete, continuous farm-to-fork system. It is of utmost importance to control faecal contamination of carcasses through efficient HACCP-based process hygiene management systems. PMID- 22062092 TI - Normative and pre-normative aspects for the management of actual and perspective POPs in meat and meat products. AB - With the acronym POPs we intend a group of persistent organic pollutants framed within the Stockholm Convention [Stockholm Convention on Persistent Organic Convention (POPs) (2004). Available from http://www.pops.int/]. POPs are a subgroup of the wide family of the aforesaid chemicals present in the environment, that are primarily of industrial origin. According to their physical chemical properties, bioaccumulative behaviour in lipid tissues, and possible toxicological effects, they represent a relevant and growing concern for human beings. Foodstuffs of animal origin represent the main source of exposure. Monitoring data from national residue plans report only few non-compliances with respect to regulatory limits. However, the estimated intake, as in the case of polychloro-p-dibenzodioxins (PCDD), polychlorodibenzofurans (PCDF) and dioxin like polychlorobyphenils (DL-PCBs) may result close to the correspondent safety guidance value (i.e., the Tolerable Daily Intake), thus indicating the need to reduce the overall exposure. In animal productions, the sources of contamination may be the commercial feedingstuffs as well as the contact with contaminated soil and bedding materials and the overall quality of the environment where animal productions are carried out. In this light, a number of safety challenges are envisaged to produce meat, such as: (a) characterization of the environment, (b) identification of the animal-based risk factors, (c) model-based approaches, able to predict bioaccumulation, and (d) teaching and training of stockmen. PMID- 22062093 TI - Tracking emerging zoonotic pathogens from farm to fork. AB - A combination of factors including changes in the agri-food chain, social changes, advances in detection and reporting systems coupled with bacterial adaptation and evolution have in recent years lead to the emergence of a number of zoonotic microorganisms in the food and water chain. These include multi antibiotic resistant bacteria, verocytotoxigenic Escherichia coli, parasites such as Cyclospora on fruit, and Cyrptosporidium and Giardia in water, Enterobacter sakazakii in infant milk formula, and emergent species of Campylobacteraceae. In this paper, Enterohaemorrhagic E. coli and Campylobacteraceae are taken as examples of emergent pathogens in the meat chain. Specific factors which may have lead to their emergence are deliberated, in addition to an overview of tools for their detection and tracking, and their epidemiology and survival characteristics. Approaches to managing and controlling emergent pathogens in the agri-food chain are also discussed. PMID- 22062094 TI - Pros and cons of carcass decontamination: The role of the European Food Safety Authority. AB - Various intervention strategies to control foodborne pathogens have been identified and applied through the whole food chain. Physical, chemical, biological treatments applied alone or in combination have been studied and proved to reduce the number and the prevalence of bacterial contamination of meat surfaces such as carcasses. The various treatments have their own advantages and disadvantages. In EU, chemical decontamination was not permitted until the recent revision of European food hygiene legislation which allows the use of substances other than water for the removal of meat surface bacterial contamination. The European Commission will authorise the use of such substances after the European Food Safety Authority (EFSA) has provided a chemical and a microbiological risk assessment. For this purpose, EFSA issued a guidance document which points out the major components and prerequisites that a study/dossier should contain in order to prove that the substance intended to be used for the removal of microbial surface contamination of foods of animal origin (i) would not pose any appreciable risk to the public health (safety or chemical assessment) and (ii) would result in a significant reduction of the prevalence and the numbers of pathogenic target bacteria when compared to the control and when this reduction is at the same time of relevance to human health (efficacy or microbiological risk assessment). The current paper deals only with microbiological safety issues. PMID- 22062095 TI - Inhibition of Salmonella sp. Listeria monocytogenes and Staphylococcus aureus in cooked ham by combining antimicrobials, high hydrostatic pressure and refrigeration. AB - Recontamination of ready-to-eat products such as cooked ham during post processing may be the cause of outbreaks of food-borne disease. The effectiveness of the combination of high pressure processing (HPP) at 600MPa with the natural antimicrobials nisin and potassium lactate has been evaluated in sliced cooked ham spiked with 4LogCFU/g of Salmonella sp., Listeria monocytogenes and Staphylococcus aureus after 3-months of storage at 1 and 6 degrees C. In non-HPP sliced cooked ham, the addition of nisin plus lactate inhibited the growth of L. monocytogenes during the entire storage period while the refrigerated storage inhibited the growth of Salmonella sp. and S. aureus. The application of an HPP reduced the levels of Salmonella and L. monocytogenes to levels below 10CFU/g. These levels continued until the end of storage at both 1 and 6 degrees C. HPP produced a reduction of less than 1LogCFU/g to S. aureus. The combination of HPP, nisin and refrigeration at 6 degrees C was necessary to decrease the levels of S. aureus by 2.4LogCFU/g after 3-months of storage. PMID- 22062096 TI - Veterinary drug residues in meat: Concerns and rapid methods for detection. AB - The use of substances having hormonal or thyreostatic action as well as beta agonists is banned in the European Union. However, sometimes forbidden drugs may be added to feeds for illegal administration to farm animals for promoting increased muscle development or increased water retention and thus obtain an economical benefit. The result is a fraudulent overweight of meat but, what is worse, residues of these substances may remain in meat and may pose a real threat to the consumer either through exposure to the residues, transfer of antibiotic resistance or allergy risk. This has exerted a great concern among European consumers. The control of the absence of these forbidden substances in animal foods and feeds is regulated in the European Union by Directive96/23/EC on measures to monitor certain substances and residues in live animals and animal products. Analytical methodology, including criteria for identification and confirmation, for the monitoring of compliance was also given in Decisions 93/256/EEC and 93/257/EEC. More recently, Decision 2002/657/EC provided rules for the analytical methods to be used in testing of official samples. A crucial step is the screening of veterinary drug residues in live animals, feeds and animal products in view of the remarkable number of samples and large variety of residues to be analysed. In recent years, different rapid methods having easy performance, high sensitivity and high throughput have been proposed and are being extensively used. These methods as well as other new methods are reviewed in this manuscript. PMID- 22062097 TI - The use and control of nitrate and nitrite for the processing of meat products. AB - Nitrate and nitrite are used for the purpose of curing meat products. In most countries the use of both substances, usually added as potassium or sodium salts, is limited. Either the ingoing or the residual amounts are regulated by laws. The effective substance is nitrite acting primarily as an inhibitor for some microorganisms. Nitrite added to a batter of meat is partially oxidized to nitrate by sequestering oxygen - thus it acts as an antioxidant - a part of nitrite is bound to myoglobin, forming the heat stable NO-myoglobin, a part is bound to proteins or other substances in meat. Nitrate may be reduced to nitrite in raw meat products by microorganisms. As oxidation and reduction may occur the concentrations of nitrite plus nitrate in a product has to be controlled and measured especially if the residual amounts are regulated. This sum of both compounds is important for the human body. Intake of nitrate with food leads to its absorption over the digestive tract into the blood. In the oral cavity nitrate appears again where it is reduced to nitrite. With the saliva the nitrite is mixed with food, having the same effect as nitrite in a batter (inhibiting growth of some pathogenic microorganisms) and swallowed. In the stomach nitrite can eventually form carcinogenic nitrosamines in the acidic environment. PMID- 22062098 TI - Meat spoilage during distribution. AB - Meat spoilage during distribution can be considered as an ecological phenomenon that encompasses the changes of the available substrata (e.g., low molecular compounds), during the prevailing of a particular microbial association, the so called specific spoilage organisms (SSO). In fact, spoilage of meat depends on an even smaller fraction of SSO, called ephemeral spoilage organisms (ESO). These ESO are the consequence of factors that dynamically persist or imposed during, e.g., processing, transportation and storage in the market. Meanwhile spoilage is a subjective judgment by the consumer, which may be influenced by cultural and economic considerations and background as well as by the sensory acuity of the individual and the intensity of the change. Indeed, when spoilage progresses, most consumers would agree that gross discoloration, strong off-odors, and the development of slime would constitute the main qualitative criteria for meat rejection. On the other hand, meat industry needs rapid analytical methods or tools for quantification of these indicators to determine the type of processing needed for their raw material and to predict remaining shelf life of their products. The need of an objective evaluation of meat spoilage is of great importance. The use of metabolomics as a potential tool for the evaluation of meat spoilage can be of great importance. The microbial association of meat should be monitored in parallel with the estimation of changes occurring in the production and/or assimilation of certain compounds would allow us to evaluate spoilage found or produced during the storage of meat under different temperatures as well as packaging conditions. PMID- 22062099 TI - Bioactive packaging technologies for extended shelf life of meat-based products. AB - To prevent the development and spread of spoilage and pathogenic microorganisms via meat foodstuffs, antimicrobial packaging materials could be a potential alternative solution. Instead of mixing antimicrobial compounds directly with food, incorporating them in films allows the functional effect at the food surface - where the microbial growth is mostly found - to be localized. Antimicrobial packagings include systems such as adding a sachet into the package, dispersing bioactive agents in the packaging, coating bioactive agents on the surface of the packaging material, or utilizing antimicrobial macromolecules with film forming properties or edible matrices. The potential of these technologies are evaluated for the preservation of meat and meat products. PMID- 22062100 TI - Meat products in the past, today and in the future. AB - An illustrative overview is given of the history of meat products, emphasizing the present situation. Three different consecutive and complementary periods can be defined in terms of realisations, threats and opportunities. The "Quality" period started about 15 years ago and was characterised by the introduction of the ISO Quality Systems Standards. A trend from product control towards system control for guaranteeing Food Safety and Quality was obvious. The "Food Safety" Period started with the introduction of HACCP. Pushed by Food Safety scandals this period is characterised by a growing influence of authorities and legislation besides an increase in distribution requirements. The "Nutrition and Health" period has only just started. Global health problems related to food and the (potential) answers of the meat industry are highlighted. For meat products the energy (fat) level, the sodium level and fat quality in terms of fatty acid composition are the main priorities. PMID- 22062101 TI - Decontamination technologies for meat products. AB - Consumers demand high quality, natural, nutritious, fresh appearance and convenient meat products with natural flavour and taste and an extended shelf life. To match all these demands without compromising safety, in the last decades alternative non-thermal preservation technologies such as HHP, irradiation, light pulses, natural biopreservatives together with active packaging have been proposed and further investigated. They are efficient to inactivate the vegetative microorganisms, most commonly related to food-borne diseases, but not spores. The combination of several non-thermal and thermal preservation technologies under the so-called hurdle concept has also been investigated in order to increase their efficiency. Quick thermal technologies such as microwave and radiofrequency tunnels or steam pasteurization bring new possibilities to the pasteurization of meat products especially in ready to eat meals. Their application after final packaging will prevent further cross-contamination during post-processing handling. The benefits of these new technologies and their limitations in an industrial application will be presented and discussed. PMID- 22062102 TI - Molecular tracking of Listeria monocytogenes in an Iberian pig abattoir and processing plant. AB - The environment and products from an Iberian pig abattoir and processing plant were sampled to investigate the prevalence and genetic diversity of Listeria monocytogenes. The organism was not detected in the pig carcasses prior to processing. Fresh and dry-cured pork did show detectable levels, always ranging below 100CFU per gram. A total of 163 L. monocytogenes isolates collected during one year were characterized by PCR-based serotyping and pulsed-field gel electrophoresis (PFGE) restriction analysis. Three predominant PFGE types or pulsotypes seemed to persist in the plant. The pulsotype S1 (serotype group 1/2a, 53% of the isolates) was mostly recovered from whole pieces of meat and environmental sites, while pulsotypes S2 (1/2a, 17%) and S4 (1/2b, 21%) were more frequently associated with ground pork products. The pulsotype S4 was also found in a grinding machine, suggesting a possible association of this machine with the contamination of the ground meat products. PMID- 22062103 TI - Microbiology and physico-chemical changes of dry-cured ham during the post salting stage as affected by partial replacement of NaCl by other salts. AB - Dry-cured ham consumption is restricted by hypertensive consumers due to its high sodium content. This constitutes an important matter for this industry, being relevant due to the current trends in consumption. In order to prevent the problems related to the high sodium intake, one of the possibilities is the total or partial replacement of sodium by other ions, such as potassium, calcium and magnesium. The aim of this study was to characterise the post-salting stage in Spanish cured ham production with the results obtained after salting with low sodium salt content. The results showed that lower sodium hams needed more time of post-salting to reach similar water activity values than those achieved by hams salted with 100% NaCl. Nevertheless, no differences in microbial counts were observed among the studied batches, although a sharp decrease in microbiota was observed when the, post-salting time was prolonged in the lower sodium hams. PMID- 22062104 TI - Effect of packaging conditions on shelf-life of ostrich steaks. AB - This study was conducted to establish the shelf-life of ostrich steaks stored in four different packaging types: (i) air exposure, (ii) vacuum, and two different modified atmospheres packages (iii) MAP: 80% CO(2)+20% N(2,) and (iv) MAP+CO: 30% CO(2)+69.8% argon+0.2% CO. Shelf-life evaluation was based on colour, lipid and hemopigments oxidation, microbial counts and sensory assessment of odour and colour. Samples stored under air exposure showed the highest lipid and hemopigments oxidation rate. Based on aerobic bacteria counts, the shelf life of ostrich steaks stored under aerobic conditions would be 8 d at most, whereas under vacuum, MAP or MAP+CO it would be 12 d. The presence of CO extends the shelf life of ostrich steaks by stabilisation of red colour measured by instrumental and sensory techniques, and maintenance of fresh meat odour by slowing down off-odour perception. PMID- 22062105 TI - Flavour profiles of dry sausages fermented by selected novel meat starter cultures. AB - Probiotic or bioprotective Lactobacillus rhamnosus strains GG, LC-705 and E-97800 as well as Pediococcus pentosaceus E-90390 and Lactobacillus plantarum E-98098 were studied for their ability to act as main fermenting organisms in the manufacturing process of dry sausages. In the preliminary tests, their abilities to produce lactic acid and biogenic amines, histamine or tyramine, were studied in MRS broth and analysed by high-performance liquid chromatography. The strains produced higher or equal amounts of lactic acid compared to control and were amine negative. During the actual fermentation process of dry sausages the numbers of inoculated bacteria increased from the level 6.5-7.0 log cfu/g to 8.0 9.0 log cfu/g. The most fast growing strains were P. pentosaceus E-90390 and the control while the growth of L. plantarum E-98098 and L. rhamnosus LC-705 were the slowest. The pH value of the sausages decreased from 5.6 to 4.9-5.0. The presence of these experimental strains as major organisms in the sausages after fermentation and ripening was confirmed on the bases of their genetic fingerprints. The flavour profiles of the experimental sausages produced by these probiotic or protective strains were similar with that produced by the commercial meat starter culture and commercial North European dry sausage recipe. PMID- 22062106 TI - Antioxidative effects of cottonseed meals as evaluated in cooked meat. AB - Cottonseed meal samples were collected from nine cottonseed oil mills in the USA. The meal samples contained 230-1,820 ppm free gossypol and 8,300-16,480 ppm total gossypol. Finely ground meals were incorporated into ground beef with 15% fat or ground lean meats (beef semimembranosus muscle and goat lean composite), at 0-3% of the final meat mixture weight. The meat mixtures were cooked to an internal temperature of 77 degrees C, aerobically refrigerated for 3 days, and analyzed for lipid oxidation using a distillation 2-thiobarbituric acid-reactive substances (TBARS) assay method. All the cottonseed meals were highly effective antioxidants in cooked meats, decreasing day-3 TBARS values by 77-91% with 3% addition. Estimated gossypol levels in the meat samples with 3% cottonseed meal were 7-55 ppm free gossypol (vs. the 450 ppm maximum limit set by the United States Food and Drug Administration for human food products) and 249-494 ppm total gossypol (vs. the 12,000 ppm maximum limit by the UN Food and Agriculture and World Health Organizations for food products). There was no significant correlation between the antioxidative efficacy of the meals and free or total gossypol levels. PMID- 22062107 TI - Lipid and protein oxidation in microsomal fraction from turkeys: influence of dietary fat and vitamin E supplementation. AB - The objectives of this study were to investigate the effects of dietary fats (6% soya oil or rapeseed oil or tallow) and alpha-tocopheryl acetate supplementation (30 ppm for control and 200 ppm for supplemented animals), on lipid and protein oxidation, induced by Fe(3+)/ascorbate, of microsomal fraction in turkey muscles (M. pectoralis major and M. sartorius). Supplementation of turkeys with alpha tocopheryl acetate increased the vitamin E content of microsomal membranes. Vitamin E supplementation strongly decreased lipid oxidation in membranal fractions when animals were fed rapeseed oil or tallow; this effect was less pronounced in animals fed soya oil. Vitamin E supplementation induced a slight decrease in protein carbonyl content, especially in animals fed soya oil. Level of protein free thiols was considerably enhanced in diet enriched with soya oil. Vitamin E supplementation had a stabilizing effect on glucose-6-phosphatase activity of microsomes when oxidized by Fe(3+)/ascorbate. No muscle effect was detected on the level of lipid and protein oxidation in membranal fractions even if M. sartorius is known to be more oxidative than M. pectoralis major. PMID- 22062108 TI - The effect of time and type of electrical stimulation on the calpain system and meat tenderness in beef longissimus dorsi muscle. AB - Effects of type and time of electrical stimulation on the calpain system, sensory and objective meat quality in the M. longissimus thoracis et lumborum from 38 pasture-fed carcasses, were investigated under conventional chilling conditions. High voltage stimulation was applied to whole carcasses at 3 min post-mortem (pm) and to sides at either 40 or 60 min pm, whilst low voltage stimulation was applied to whole carcasses at 3 min pm and to sides at 40 min pm. Unstimulated sides served as controls. The levels of extractable MU-calpain and calpastatin decreased during stimulation by 28-44% and 8-17%, respectively. Shear force and adjusted tenderness score showed that stimulation at 3 min, irrespective of type of stimulation, resulted in significantly tougher meat (P<0.05) which was associated with an rapid rate of pH decline, compared to stimulation at 40 min. Higher calpastatin levels soon after stimulation at 3 min (P < 0.05) and lower MU calpain level at 24 h pm for high voltage stimulation at 3 min (P<0.05) coincided with the tougher meat. On the other hand, high voltage stimulation at 40 and 60 min resulted in similar tenderness and levels of MU-calpain and calpastatin post stimulation and 24 h pm. Significantly tougher meat from the control sides, with a higher MU-calpain levels at 24 h pm and similar sarcomere length, compared to those from low voltage stimulation at 40 min (P<0.001), appeared to be linked to the later activation of the calpain system. Results from the current study suggest that early application of stimulation may be associated with a very rapid decline in pH and consequently a reduction in meat quality. PMID- 22062109 TI - Determination of meat pH - temperature relationship using ISFET and glass electrode instruments. AB - pH measurements of beef, pork and lamb were made over the range 0-35 degrees C in order to establish the dependence of pH on temperature (DeltapH/DeltaT). Measurements were made using a newly developed ISFET pH probe and a conventional glass probe. The results indicated values of DeltapH/DeltaT in the range of 0.006 to -0.007 pH units/ degrees C, and are compared to the few other values of DeltapH/DeltaT reported for meat and to values generally reported in physiological studies of animal tissue. It is suggested that in meat studies and in industrial monitoring of pH, greater attention be given to potential sources of error that can arise from unrecognised temperature-related pH effects. It is also suggested that consideration be given by the industry to establishing an agreed temperature at which meat pH is reported so that valid comparisons of different pH measurements may be made. PMID- 22062110 TI - Comparison of the color stability and lipid oxidative stability of fresh and vacuum packaged lamb muscle containing elevated omega-3 and omega-6 fatty acid levels from dietary manipulation. AB - A series of three experiments were conducted with second cross ([Merino*Border Leicester]*Poll Dorset) wether lambs to evaluate the effects of dietary treatments on manipulation of muscle long-chain (LC) omega-3 fatty acids (FA) on the color stability and oxidative stability of fresh and vacuum packaged lamb. At the end of 7-, 6- and 6-week experimental periods for experiments (Exp.) 1-3 respectively, lambs were slaughtered at a commercial abattoir. At 24 h post mortem, muscle longissimus lumborum (LL) and longissimus thoracis (LT) were removed and evaluated for color and lipid oxidative stability under specified commercial storage and display condition. Of the dietary supplements used, fish meal and fish oil moderately (P<0.01) and markedly (P<0.001) increased muscle omega-3 FA content, while both protected canola seed (P<0.001) and protected sunflower meal protein significantly (P<0.02) increased muscle omega-6 FA content or ratio of omega-6/omega-3 of the longissimus muscle. In all experiments, the substantial increase (P<0.001) in muscle LC omega-3 and omega-6 FA had no consistent significant effect on color values (redness (a*), yellowness (b*) and lightness (L*)) for fresh and vacuum packaged lamb over a 6-day display period. Lipid oxidation, determined by the levels of thiobarbituric acid reactive substances (TBARS) indicated the enrichment of muscle polyunsaturated fatty acid (PUFA) levels in lambs did not produce significant differences resulting either from main treatment effects or for treatment*day*type interactions (where type was fresh and vacuum packaged). Present results demonstrated the color and lipid oxidative stability of lamb longissimus muscle during refrigerated display was not affected by enhanced levels of omega-3 and omega-6 FA due to dietary treatments. PMID- 22062111 TI - Biogenic amines produced by Enterobacteriaceae isolated from meat products. AB - Biogenic amines in ground meat and processed meat products are one of the indicators to determine the poor quality raw material. Major histamine forming bacterium was Escherichia coli (strain EC04 with 65.88 mg/100 ml in Brain Heart Infusion medium), followed by the microorganisms Morganella morganii (strain MM4 with 8.40 mg/100 ml and strain MM7 with 8.28 mg/100 ml) and Proteus mirabilis (strain PM02 with 8.76 mg/100 ml), respectively. The highest putrescine production level was found in Citrobacter freundii and Enterobacter spp. strains, followed by Serratia grimesii, Proteus alcalifaciens, E. coli, Escherichia fergusonii, Morganella morganii, Proteus mirabilis, Proteus penneri and Hafnia alvei, respectively. The most important cadaverine producer was E. coli EC03 with a production level of 45.48 mg/100 ml, and of the strains Escherichia vulnaris EV01, Escherichia fergusonii EF06 produced 37.92 mg/100ml and 35.40 mg/100 ml, respectively. On the basis of our results, it can be concluded that the major biogenic amines produced by Enterobacteriaceae are putrescine, cadaverine, tyramine and histamine, both in culture medium and meat products. PMID- 22062112 TI - The interaction between pH and temperature decline early postmortem on the calpain system and objective tenderness in electrically stimulated beef longissimus dorsi muscle. AB - The study investigated the effects of pH and temperature decline early postmortem (pm) on calpains and calpastatin activities and objective tenderness in M. longissimus thoracis et lumborum. A total of 40 sides were used to generate a range of pH and temperature declines, by different stimulation treatments (i.e. low voltage stimulation applied for either 10 or 40 s 3 min pm), and chilling treatments (fast or slow). Both rapid glycolysis, or a slow chilling regime significantly reduced MU-calpain level at 4 h pm (P< 0.001 and P< 0.05, respectively). There were significant interactions between pH and temperature at 1.5 h pm on MU-calpain and calpastatin activities at 24 h pm (P< 0.05). Rapid glycolysis resulted in lower shear force and compression measurements at day 1, although because of low ageing rates, an intermediate pH decline (i.e. pH 5.9-6.2 at 1.5 h pm) resulted in the most tender meat after 14 days ageing. Higher shear forces in the slow glycolysing sides appeared to be associated with the later activation of tenderising process, as well as physical shortening. The optimum pH decline early pm varied with days ageing, with an intermediate pH decline resulting in the lower shear forces for meat aged for 14 days. PMID- 22062113 TI - Study of the branched hydrocarbon fraction of intramuscular lipids from Iberian fresh ham. AB - Branched hydrocarbons from the unsaponifiable lipid fraction of the Biceps femoris muscle of Iberian pigs were analyzed. Fifty-five Iberian pigs were distributed to seven groups according to management system (short Montanera and long Montanera, i.e. fed on acorn and pasture for 55 and 75 days prior to slaughter, respectively, and Pienso, fed on a concentrate diet), and genetic type. A branched hydrocarbon, neophytadiene, was identified only in samples from the pigs fed on the extensive system, with higher levels being found in pigs from the long Montanera group, than in those from the short Montanera group; this compound was not found in the Pienso group. Genotype did not affect the level of branched hydrocarbons found. PMID- 22062114 TI - The effect of breed-production systems on the myosin heavy chain 1, the biochemical characteristics and the colour variables of Longissimus thoracis from seven Spanish beef cattle breeds. AB - The effect of breed-production system on the myosin heavy chain 1 (MHC-I), the biochemical characteristics and the colour variables of longissimus thoracis (LT) from seven beef breeds was studied: Asturiana de la Montana (AM), Asturiana de los Valles (AV), Avilena-Negra Iberica (A-NI), Bruna dels Pirineus (BP), Morucha (MO), Pirenaica (PI) and Retinta (RE) (Age at slaughter between 368 and 541 days; carcass weight between 249 and 334 kg). Significant differences between breed production systems were found for all traits evaluated. LT from the MO, a rustic type breed, was the most oxidative (MHC-I, 39.3%; isocitrate dehydrogenase activity, 52 nmol min(-1) mg(-1); pigment content, 188.4 MUg acid haematin g(-1)) and showed a low L* value (32.6) and high a* and C* values (24 and 27.2, respectively). In terms of meat colour (L* and a*) the canonical discriminant analysis separated the breeds into two groups, the AV, the PI and the A-NI (the lightest ones) from the AM and the MO breeds (the reddest and darkest) whereas the BP showed an intermediate position. The RE and the A-NI were distinguished from the others by their high intramuscular fat content. Meat colour was affected by the muscle biochemical traits in the breed-production systems studied. PMID- 22062115 TI - Improvement of the physicochemical properties of pale soft and exudative (PSE) pork meat products with an extract from mechanically deboned turkey meat (MDTM). AB - Loss of protein functionality of pale soft and exudative (PSE) meat and a surplus of mechanically deboned turkey meat (MDTM) has negative economic impacts on the meat industry. The objective of this research was to add functional proteins from an extract of MDTM to PSE meat to create a value-added pork sausage product. Sausages manufactured from PSE incorporating an MDTM extract exhibited a 30% increase in rigidity (P<0.05) compared to those manufactured using brine alone. Sausages made from PSE and normal pork with the MDTM extract demonstrated little difference in water holding capacity (P>0.05), and reductions of 4.1 and 3.1% in cooking loss (P<0.05), respectively, compared to sausages made employing brine alone. Introducing functional proteins derived from MDTM to processed meat made with PSE pork has the potential to enhance the economic value to both of these low value raw materials. PMID- 22062116 TI - Pork meat quality affects peptide and amino acid profiles during the ageing process. AB - Twenty pork carcasses were classified in different pork meat qualities: red, firm and non-exudative (RFN), pale, soft and exudative (PSE), red, soft and exudative (RSE) and dark, firm and dry (DFD) meat. The content of peptides and free amino acids during the ageing process was analysed and compared within quality classes. Four peptide fractions were isolated through cation-exchange and reverse-phase chromatography. The main significant differences among qualities were obtained for peptide fractions 3 and 4. Peptide fraction 3 at 4 days and peptide fraction 4 at 2 h postmortem were higher in the ideal pork quality (RFN) than in the other quality classes. The ageing of pork meats produced a general increase in all free amino acid concentrations for the studied quality classes except for Gln, beta Ala, Taurine and Orn and the dipeptides carnosine and anserine. The DFD class showed higher increases in Lys, Ala and Met probably due to the activation of neutral aminopeptidases. PMID- 22062117 TI - Diverse lamb genotypes 4. Predicting the yield of saleable meat and high value trimmed cuts from carcass measurements. AB - To determine how current predictors of carcass and cut yield perform in the Australian lamb industry a large study was undertaken using diverse genotypes. Carcass measurements and yield data were obtained for 591 lambs representing two sexes (cryptorchids, ewes). The lambs were sired by a selection of Texel (T), Poll Dorset (PD), Border Leicester (BL) and Merino (M) rams crossed with Border Leicester*Merino (BLM) and Merino (M) ewes giving six genotypes (T*BLM, PD*BLM, T*M, PD*M, BL*M, M*M). The percentage yield of saleable meat, hindquarter, loin and a range of trimmed cuts were predicted using models based on hot carcass weight, EUROP conformation score, m. longissimus thoracis et lumborum area (LL area) in combination with three different measures of carcass fatness: (1) the depth of muscle and fat tissue from the surface of the carcass to the lateral surface of 12th rib, 110 mm from the midline (GR); (2) fat depth over the LL at the deepest part of the muscle (FATC); and (3) fat depth at the 5th rib, 110 mm from the midline (FAT5). FAT5 was identified as the most accurate and robust (stable) fat measurement for the prediction of saleable meat yield in a production system based on diverse genotypes. Using GR as a fatness measurement led to overestimation of fatness level and underestimation of yield in T sired lambs. Conformation score after carcass weight and any of the fat measurements improved (P<0.01) the prediction of the yield of saleable meat, hindquarter, loin and all trimmed lamb cuts with the exception of the ribloin (rack). LL area added significantly (P<0.01) to the prediction of the yield of saleable meat, hindquarter and trimmed lamb cuts, but not for the midloin and neck fillet at a constant carcass weight and fatness. Large proportions of the variation in all yields were unaccounted for, even after the inclusion of either conformation or LL area. Predictions based on carcass weight and any of the three different fat measurements were not very accurate. Although the addition of LL area as a predictor significantly (P<0.01) increased the accuracy of the predictions the results suggest that the current description system for lamb carcases in Australia needs to be re-examined. PMID- 22062118 TI - Erratum. PMID- 22062119 TI - Immobilization of lipase on cotton cloth using the layer-by-layer self-assembly technique. AB - Lipase from Thermomyces lanuginosus was assembled into multiple layers on polyethylenimine treated cotton flannel cloth, utilising the enzymes property of forming bimolecular aggregates via layer-by-layer (LBL) immobilization technique. An increase in lipase activity with increasing enzyme layers confirmed lipase aggregation. A study to compare the activity of enzyme bound by classical LBL technique, containing alternate layers of polyethylenimine and lipase and the modified approach indicated above, showed that more enzyme was bound to cloth in the modified approach. A total of 13 U/cm(2) of enzyme were bound to cloth till the fifth layer whereas only 10.2 U/cm(2) were bound till the fifth bilayer in the classical approach. The successful assembly of lipase molecules has shown that this modified technique is a promising approach to immobilize enzymes that aggregate through hydrophobic interactions as nano-films on cloth. PMID- 22062120 TI - Interpenetrating polymer network (IPN) hydrogel microspheres for oral controlled release application. AB - Interpenetrating polymer network (IPN) hydrogel microspheres of sodium carboxymethyl cellulose (NaCMC) and poly(vinyl alcohol) (PVA) were prepared by water-in-oil (w/o) emulsion crosslinking method for oral controlled release delivery of a non-steroidal anti-inflammatory drug, diclofenac sodium (DS). The microspheres were prepared with various ratios of NaCMC to PVA, % drug loading and extent of crosslinking density at a fixed polymer weight. The prepared microspheres with loose and rigid surfaces were evidenced by scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the IPN formation. Differential scanning calorimetry (DSC) study was performed to understand the dispersion nature of drug after encapsulation. The in vitro drug release study was extensively evaluated depending on the process variables in both acid and alkaline media. All the formulations exhibited satisfactory physicochemical and in vitro release characteristics. Release data indicated a non-Fickian trend of drug release from the formulations. Based on the results of this study suggest that DS loaded IPN microspheres were suitable for oral controlled release application. PMID- 22062121 TI - The effect of corn distiller's dried grains with solubles, ractopamine, and conjugated linoleic acid on the carcass performance, meat quality, and shelf-life characteristics of fresh pork following three different storage methods. AB - The objective of this study was to evaluate dietary corn distiller's dried grains with solubles (DDGS), ractopamine hydrochloride (RAC), and conjugated linoleic acid (CLA) on growth performance, carcass and fat quality, and shelf-life of fresh pork from finishing pigs. Barrows (n=72) were fed one of eight treatments consisting of two diet sources (corn-soy and corn-soy+20% DDGS), two levels of RAC (0 and 7.4ppm), and two levels of CLA (0 and 0.6%) for 28days. Loins were portioned (n=3) into one of three storage conditions (fresh, cold, frozen); each followed with seven days of retail display. Feeding RAC improved ADG and G:F (P<0.05), whereas DDGS decreased belly fat firmness (P<0.05). Dietary DDGS increased total polyunsaturated fatty acids in jowl and belly samples and increased Iodine Value (IV) (P<0.05), but addition of CLA decreased IV. Dietary DDGS, RAC, or CLA had minimal impact on pork quality following varied storage methods. PMID- 22062122 TI - Molecular characterization and expression analysis of interferon regulatory factor 5 (IRF-5) in turbot, Scophthalmus maximus. AB - Interferon regulatory factor 5 (IRF-5) plays a role both in the antiviral and inflammatory responses. In this study, we described the structure, mRNA tissue distribution and regulation of an IRF-5 gene from turbot, Scophthalmus maximus (SmIRF-5). The gene sequence of SmIRF-5 is 4275 bp long, composed of 9 exons and 8 introns similar to known IRF-5 genes of vertebrates, and encodes a peptide of 487 amino acids. The deduced protein sequence shares the highest identity of ~60 70% with fish IRF-5 and possesses a DNA-binding domain (DBD), a middle region (MR), an IRF association domain (IAD) and a virus activated domain (VAD) known to be important for the functions of IRF-5 in mammals. Phylogenetic analysis grouped SmIRF-5 with other IRF-5s of vertebrates. SmIRF-5 transcripts were detectable in a wide range of tissue types of healthy fish with higher levels observed in the head kidney, kidney and spleen. The SmIRF-5 was transcriptionally up-regulated by turbot reddish body iridovirus (TRBIV) but not by polyinosinic:polycytidylic acid (poly I:C) in the gills, head kidney, spleen and muscle. Both the highest inducibility and earliest induction of SmIRF-5 expression were observed in the spleen where it reached a maximum level at day 1 after infection, prior to that of turbot Mx. These findings may help to better understand the roles of SmIRF-5 in antiviral response. PMID- 22062123 TI - Effects of high pressure on meat: A review. AB - Extensive investigations in the last decade have revealed the potential benefits of high pressure processing (100-800 MPa) for the preservation and modification of foods. Simultaneously, a few pressurised foods have become commercially available in Japan, Europe and the USA. In the present review, the basic principles underlying the effects of high pressure on food constituents and quality attributes are first presented. Recent data concerning the following specific effects of high pressure on muscle and meat products are then reported and discussed: changes in muscle enzymes and meat proteolysis; modifications in muscle ultrastructure; effects on myofibrillar proteins; meat texture and pressureassisted tenderisation processes; pressure-induced gelation and restructuring of minced meat; changes in myoglobin and meat colour; influence of pressure on lipid oxidation in muscle; high pressure-inactivation of pathogenic and spoilage micro-organisms in meat; combined high pressure-moderate temperature 'pasteurisation' of meat products. PMID- 22062124 TI - Quality improvement of ground buffalo meat by preblending with sodium ascorbate. AB - Ground buffalo meat (GBM) was preblended with sodium ascorbate (SA) at 0, 300, 400, 500 and 600 ppm level and was examined for its quality changes during refrigerated storage at 4+/-1 degrees C. It was observed that GBM containing 500 ppm SA had significantly higher pH, visual colour and odour, lovibond tintometer red colour units (LTCU 'R') and chroma; lower cooking loss, metmyoglobin content and TBARS number as compared with other levels of SA. TBARS number was highly correlated with metmyoglobin and inversely with odour score; visual colour was negatively correlated with metmyoglobin, aerobic mesophiles count and psychrotrophs plate count. SA at 500 ppm is found to be optimum level for preblending which extended the shelf life of GBM from 4 to 8 days under refrigerated storage. PMID- 22062125 TI - Acute phase response in emergency slaughtered dairy cows. AB - The acute phase response and the diagnostic value of two serum acute phase proteins, haptoglobin and alpha(1)-acid glycoprotein, were studied in eighty emergency slaughtered Ayrshire or Friesian dairy cows. The results were compared with plasma proteins and enzymes and with the meat inspection data of the slaughtered cows. Cows with minor injuries, such as teat lesions, had low haptoglobin and alpha(1)-acid glycoprotein serum concentrations, the means being 0.01 and 0.54 gl(-1). The other emergency slaughtered animals exhibited acute phase response: the means for haptoglobin and alpha(1)-acid glycoprotein were 0.67 and 0.96 gl(-1), respectively. Serum gammaglobulin was also increased in these animals, and had a mean concentration of 22 gl(-1). These results indicate that acute phase proteins could be used for detecting diseased animals from the normal slaughterhouse material. Haptoglobin and alpha(1)-acid glycoprotein did not quantitatively predict the meat inspection result of the emergency slaughtered dairy cows. Serum gamma-globulin concentration was more effective in this respect, being significantly higher (p < 0.05) in totally condemned carcases. Muscle traumas were the most frequent pathological finding in meat inspection. They also induced an acute phase response detectable by serum haptoglobin and alpha(1)-acid glycoprotein. Alpha(1)-acid glycoprotein correlated positively with the quantity of muscle trauma, the correlation coefficient being 0.54 (p < 0.01). The respective correlations for muscle specific enzymes serum aspartate aminotransferase and creatine kinase were 0.62 and 0.63 (p < 0.01). PMID- 22062126 TI - Muscle metabolic traits, post mortem-pH-decline and meat quality in pigs subjected to regular physical training and spontaneous activity. AB - Ninety-six female and male pigs were assigned to one of three treatments, 'confined' (C),'trained'(T) or 'free' (F) allowing for different levels of physical activity during the growth interval from 30 to 100kg. Treatment C consisted of individual housing in pens of 2.5 m(2); treatment T of individual housing and regular treadmill training and treatment F of housing in pens of 36 m(2) (40 pigs/pen). In m. biceps femoris (BF), the activity of lactate dehydrogenase (LDH) was decreased between 9 and 12% by training (treatment T vs C). Likewise, in BF from female pigs, training increased the activity of citrate synthase (CS) and of 3-OH-acyl-CoA-dehydrogenase (HAD) by 18 and 21%, respectively. Spontaneous activity (treatment F) reduced the activity of LDH for five muscles between 10 and 16% when compared with treatment C. Around the time of slaughter, glycogenolysis of BF was less for treatment F (6-17%) than for C and T (33-38%). Moreover, in BF from female pigs in treatment F, the initial but not the ultimate pH was increased when compared with treatment C. In comparison to C and T, treatment F improved juiciness in BF from male pigs and increased the amount of salt soluble protein in m. longissimus dorsi. PMID- 22062127 TI - Dry fermented sausages elaborated with Lactobacillus plantarum-staphylococcus carnosus. Part II: Effect of partial replacement of NaCl with KCl on the proteolytic and insolubilization processes. AB - The effect of partial replacement of NaCl with KCl (3% NaCl by 1.5% NaCl + 1% KCl) on the proteolytic and insolubilization processes that affect the nitrogen fractions of dry fermented sausages produced with L. plantarum-S. carnosus as starter culture was analysed. The percentage of solubility was significantly lower in the modified product, which is consistent with its significantly higher percentage of insoluble fraction observed from the beginning of the process. The myofibrillar fraction was more affected by the proposed modification than the sarcoplasmic fraction: the loss of solubility for the modified and control products were 33.6 and 27.6% for myofibrillar fraction and 9.9 and 9.3% for the sarcoplasmic fraction, respectively. Also a higher intensity of the proteolytic process was observed. The modified product was found to be slightly less hard but had a better salted taste. PMID- 22062128 TI - Mechanical and structural characteristics of single muscle fibres and fibre groups from raw and cooked pork longissimus muscle. AB - The aim of this study was to analyse the mechanisms that determine why small groups of muscle fibres may have different mechanical properties than single muscle fibres. The method used combined light microscopy and tensile testing on single fibres and small groups of fibres from raw and cooked (80 degrees C) meat, from both conditioned and unconditioned porcine longissimus muscle. The results showed that small groups of fibres had different breaking properties than constituent single fibres in raw muscle, but that these differences diminished on cooking. Raw groups of fibres showed a more uniform lengthening along their entire length and a higher extension to rupture than single fibres. Conditioning increased maximum strains in both single fibres and small fibre groups. In unconditioned cooked meat, single fibres and fibre groups showed comparable breaking stresses and extensions. Conditioning resulted in a lower strength in fibre groups than in single fibres. These results show that (endomysial) connective tissue linkages between adjacent muscle fibres in a small group significantly alter the breaking behaviour of single fibres. The effects of these connective tissue linkages are not reduced by conditioning alone, but are largely diminished by cooking to 80 degrees C. PMID- 22062129 TI - The extraction and properties of superoxide dismutase from porcine blood. AB - Crude Superoxide dismutase (SOD) was prepared by extraction with chloroform ethanol, centrifugation and acetone precipitation. The specific activity of the SOD was 1570 units mg(-1), and an unusual ultraviolet spectrum with maximum absorbance at 256.4 nm was observed. When the SOD was kept at 40, 50 and 60 degrees C for 10 min, it showed little loss of stability but it retained only 95, 69, 45 and 2.5% of its original activity after holding at 60, 70, 75, and 80 degrees C for 5 min., respectively. When cupric ions were added, the thermostability of SOD was enhanced. When the extracted SOD was kept at -23, 4, 25 and 30 degrees C for 20 weeks, the relative activity retained was 76, 67, 26 and 16%, respectively. Using the sensitive test with cyanide and hydrogen peroxide, the acrylamide gel of the SOD showed this enzyme was of the Cu Zn type. The molecular weights of the holoenzyme and its subunits, estimated by SDS polyacrylamide gel electrophoresis, were approximately 31 and 15 kD, respectively. PMID- 22062130 TI - Role of neutrophils in acrylonitrile-induced gastric mucosal damage. AB - Acrylonitrile (ACN) is a widely used intermediate in the manufacture of plastics, acrylic fibers, synthetic rubbers and resins that are used in a variety of products including food containers and medical devices. ACN is a possible human carcinogen and a documented animal carcinogen, with the stomach being an important target of its toxicity. ACN has been previously reported to require metabolic activation to reactive intermediates and finally to cyanide (CN-). The current study aimed at exploring the potential role of neutrophils in ACN-induced gastric damage in rats. Experimental neutropenia was attained by injecting rats with methotrexate. This significantly ameliorated gastric mucosal injury induced by ACN. This is evidenced by protection against the increase in gastric ulcer index, myeloperoxidase (MPO) activity and CN- level. Also, neutropenia guarded against the decrease in prostaglandin E2 (PGE2), induction of oxidative stress and reduction of total nitrites and alleviated histopathological alterations in rat stomachs. These data indicate that neutrophil infiltration is, at least partly, involved in ACN-induced gastric damage in rats. PMID- 22062131 TI - Potential estrogenic activity of triclosan in the uterus of immature rats and rat pituitary GH3 cells. AB - Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS) is used as an antimicrobial agent in personal care, pharmaceutical, industrial, and household products. In this study, we established an in vivo model for screening estrogenic activity of TCS in the uteri of immature rats. In addition, we employed temporarily transfected cells with plasmids containing estrogen response element (ERE) and progesterone (P4) response element (PRE) sequences. We found that uterine weight was significantly increased by 17alpha-ethinylestradiol (EE) as a positive control and TCS at doses of 7.5, 37.4, and 187.5 mg/kg. In addition, the expressions of calbindin-D(9k) (CaBP-9k) and complement C3 (C3) were significantly induced by EE and TCS in the uteri of immature rats, indicating that TCS can induce their expression mediated by estrogenic activity. Co treatment with steroid antagonists ICI 182,780 (ICI) and RU 486 in conjunction with TCS (37.5 mg/kg) reversed TCS-induced uterine weight and CaBP-9k mRNA and protein expression increases in immature rats. Moreover, ERE and PRE luciferase activity was evaluated in GH3 cells following treatment with TCS. Concentrations of TCS at increasing doses (10-9, 10-7, and 10-5 M) resulted in a significant increase in ERE luciferase activity compared to control; however, no difference was observed in PRE luciferase activity following TCS treatment. To confirm that ER signaling is involved in TCS-induced CaBP-9k expression, we treated GH3 cells with the anti-estrogen ICI, which can block TCS-induced up-regulation of CaBP-9k in these cells. Taken together, these results indicate that TCS has an estrogen like property, which may be mediated through an ER-involved signaling pathway in both in vivo and in vitro models. PMID- 22062132 TI - Evidence of a suffocation alarm system within the periaqueductal gray matter of the rat. AB - Dyspnea, hunger for air, and urge to flee are the cardinal symptoms of panic attacks. Patients also show baseline respiratory abnormalities and a higher rate of comorbid and antecedent respiratory diseases. Panic attacks are also precipitated by infusion of sodium lactate and inhalation of 5% CO2 in predisposed patients but not in healthy volunteers or patients without panic disorder. Accordingly, Klein [Klein (1993) Arch Gen Psychiatry 50:306-317] suggested that clinical panic is the misfiring of an as-yet-unidentified suffocation alarm system. In rats, selective anoxia of chemoreceptor cells by potassium cyanide (KCN) and electrical and chemical stimulations of periaqueductal gray matter (PAG) produce defensive behaviors, which resemble panic attacks. Thus, here we examined the effects of single or combined administrations of CO2 (8% and 13%) and KCN (10-80 MUg, i.v.) on spontaneous and PAG-evoked behaviors of rats either intact or bearing electrolytic lesions of PAG. Exposure to CO2 alone reduced grooming while increased exophthalmus, suggesting an arousal response to non-visual cues of environment. Unexpectedly, however, CO2 attenuated PAG-evoked immobility, trotting, and galloping while facilitated defecation and micturition. Conversely, KCN produced all defensive behaviors of the rat and facilitated PAG-evoked trotting, galloping, and defecation. There were also facilitatory trends in PAG-evoked exophthalmus, immobility, and jumping. Moreover, whereas the KCN-evoked defensive behaviors were attenuated or even suppressed by discrete lesions of PAG, they were markedly facilitated by CO2. Authors suggest that the PAG harbors an anoxia-sensitive suffocation alarm system which activation precipitates panic attacks and potentiates the subject responses to hypercapnia. PMID- 22062134 TI - Changes in hippocampal synapses and learning-memory abilities in a streptozotocin treated rat model and intervention by using fasudil hydrochloride. AB - Fasudil hydrochloride (FH), a Rho kinase inhibitor, is used to treat neurological diseases. This study aims to elucidate the anti-dementia role of FH in Alzheimer's disease. Twenty-four Sprague-Dawley rats were randomly divided into four groups: (1) sham-operated group (control), (2) sham-operated followed by FH administration group (sham+FH), (3) streptozotocin (STZ)-treated group (STZ), and (4) STZ treatment followed by FH administration group (STZ+FH). Rats in the STZ and STZ+FH groups received two divided doses of STZ (1.5 mg/kg) intracerebroventricularly on days 1 and 3, whereas control and sham+FH group rats were given citric acid/sodium citrate buffer. Rats in the sham+FH and STZ+FH groups were then treated intraperitoneally with FH (10 mg/kg) for 4 weeks, and rats in the STZ and control groups were treated with saline. Learning and memory were measured using the Morris water maze test. The synaptic ultrastructure in the CA1 region of the hippocampus was observed using electronic microscopy. The expression of synaptophysin (SYP) was measured using real-time polymerase chain reaction and western blot analyses; the expression of p-LIMK2 and p-cofilin were also detected using western blot analysis. The results indicate that STZ induced deficit in learning/memory, decrease in SYP expression, degeneration in synaptic structures, and increase in the expressions of p-LIMK2 and p-cofilin. These changes were reversed by the administration of FH, suggesting that FH has anti dementia properties that protect synaptic structure and function. FH induced dephosphorylation (inactivation) of LIMK2 and subsequent dephosphorylation (activation) of cofilin, which may be responsible for the amelioration of neuronal synaptic structure and function. PMID- 22062133 TI - Microglial stress inducible protein 1 promotes proliferation and migration in human glioblastoma cells. AB - Microglial activation is a key event in the progression and infiltration of tumors. We have previously demonstrated that the co-chaperone stress inducible protein 1 (STI1), a cellular prion protein (PrP(C)) ligand, promotes glioblastoma (GBM) proliferation. In the present study, we examined the influence of microglial STI1 in the growth and invasion of the human glioblastoma cell line GBM95. We demonstrated that soluble factors secreted by microglia into the culture medium (microglia conditioned medium; MG CM) caused a two-fold increase in the proliferation of GBM95 cells. This effect was reversed when STI1 was removed from the MG CM. In this context, we have shown that microglial cells synthesize and secrete STI1. Interestingly, no difference was observed in proliferation rates when GBM cells were maintained in MG CM or MG CM containing an anti-PrP(C) neutralizing antibody. Moreover, rec STI1 and rec STI1(Delta230 245), which lack the PrP(C) binding site, both promoted similar levels of GBM95 proliferation. In the migration assays, MG CM favored the migration of GBM95 cells, but migration failed when STI1 was removed from the MG CM. We detected metalloproteinase 9 (MMP-9) activity in the MG CM, and when cultured microglia were treated with an anti-STI1 antibody, MMP-9 activity decreased. Our results suggest that STI1 is secreted by microglia and favors tumor growth and invasion through the participation of MMP-9 in a PrP(C)-independent manner. PMID- 22062135 TI - New insights into opioid regulatory pathways: influence of opioids on Wnt1 expression in zebrafish embryos. AB - Opioids are the most potent analgesics known today, but their prolonged administration produces severe adverse effects such as constipation, bradycardia, besides addiction, a concept not fully understood at present, which represents one of the most important challenges of modern bioscience. Wnts constitute an important family of vertebrate genes that encode secreted signaling proteins implicated in various developmental processes (patterning of the neural tube, neuronal differentiation), and are extensively conserved through evolution. In this study we have focused on Wnt1, an essential signal in axis polarity, as well as in proliferation and the development and differentiation of the CNS, roles shared by opioid receptors. Our previous studies in zebrafish show that morphine, the most potent analgesic known today, increases cell proliferation and induces neuronal protection and dopaminergic differentiation by activating the opioid receptors. The aim of the present study is to determine whether these effects are a consequence of an interaction between Wnt1 and the endogenous opioid system, which may act as a transcription regulator of Wnt1. Hence, we have exposed embryos to morphine, the endogenous delta opioid agonist Met-Enkephalin-Glu-Tyr (MEGY) (it binds with high affinity to both zebrafish delta opioid receptors, ZfDORs), and SNC80, a highly specific delta agonist, which displays low affinity towards the ZfDORs. Although at earlier stages, all opioids reduced the expression level of Wnt1, further on development, mainly during the differentiation of the CNS (24-48 h post fertilization (hpf)), morphine and MEGY increased Wnt1 expression. Our results point to the possibility that opioid signaling controls the transcription of Wnt1 and that through Wnt1, the opioid system regulates cell proliferation and neuronal differentiation. The present work opens a door to the discovery of new mechanisms that regulate opioid activity and its adverse effects, and hence, it might provide a good target to design new drugs that prevent or avoid these effects. PMID- 22062136 TI - Differential protection of neuromuscular sensory and motor axons and their endings in Wld(S) mutant mice. AB - Orthograde Wallerian degeneration normally brings about fragmentation of peripheral nerve axons and their sensory or motor endings within 24-48 h in mice. However, neuronal expression of the chimaeric, Wld(S) gene mutation extends survival of functioning axons and their distal endings for up to 3 weeks after nerve section. Here we studied the pattern and rate of degeneration of sensory axons and their annulospiral endings in deep lumbrical muscles of Wld(S) mice, and compared these with motor axons and their terminals, using neurone-specific transgenic expression of the fluorescent proteins yellow fluorescent protein (YFP) or cyan fluorescent protein (CFP) as morphological reporters. Surprisingly, sensory endings were preserved for up to 20 days, at least twice as long as the most resilient motor nerve terminals. Protection of sensory endings and axons was also much less sensitive to Wld(S) gene-copy number or age than motor axons and their endings. Protection of gamma-motor axons and their terminals innervating the juxtaequatorial and polar regions of the spindles was less than sensory axons but greater than alpha-motor axons. The differences between sensory and motor axon protection persisted in electrically silent, organotypic nerve-explant cultures suggesting that residual axonal activity does not contribute to the sensory-motor axon differences in vivo. Quantitative, Wld(S)-specific immunostaining of dorsal root ganglion (DRG) neurones and motor neurones in homozygous Wld(S) mice suggested that the nuclei of large DRG neurones contain about 2.4 times as much Wld(S) protein as motor neurones. By contrast, nuclear fluorescence of DRG neurones in homozygotes was only 1.5 times brighter than in heterozygotes stained under identical conditions. Thus, differences in axonal or synaptic protection within the same Wld(S) mouse may most simply be explained by differences in expression level of Wld(S) protein between neurones. Mimicry of Wld(S)-induced protection may also have applications in treatment of neurotoxicity or peripheral neuropathies in which the integrity of sensory endings may be especially implicated. PMID- 22062137 TI - Combined effects of chilling rate, low voltage electrical stimulation and freezing on sensory properties of bovine M. longissimus dorsi. AB - The single and combined effects of low voltage electrical stimulation (LVES), chilling rate after slaughter, and freezing/thawing during ageing on the tenderness of bovine M. longissimus dorsi were studied. Of 27 young bulls, 14 were exposed to LVES (90 V, 32 s, 15 Hz) immediately after stunning. Four different treatments regarding chilling rate and freezing/thawing were randomly assigned to each of the 27 young bulls. Samples were aged for 7 days at 4 degrees C and analyzed after freezing and thawing. The experimental design allowed direct comparison of different treatment effects and an assessment whether these were additive or not. As expected chilling rate after slaughter had highly significant effects on final tenderness, based on results from a trained sensory panel and Warner Bratzler (WB) shear press analysis. The effect of LVES on final tenderness was not statistically significant. The introduction of a freezing/thawing step during ageing did not significantly affect tenderness. The effects of individual treatments depended on the tenderness level and were relatively larger at high WB shear press values (7-8 kg/cm(2)) than at low values (4-5 kg/cm(2)). The results indicate that the treatment effects were not additive, but that the treatments are alternatives to tenderize beef. PMID- 22062138 TI - Hind-limb protein metabolism and calpain system activity influence post-mortem change in meat quality in lamb. AB - This study is concerned with the rate of protein turnover in the hind limb muscle bed of intact lambs, the activity of calpain proteolytic system in the M. biceps femoris, and subsequent rates of myofibre breakdown and tenderisation in the M. longissimus dorsi. Feed restriction increased protein degradation in hind-limb muscle of lambs (p<0.1), with a concominant decrease in the extractable activity of calpastatin (p<0.01), the endogenous inhibitor of calpain. IGF-1 analog treatment decreased both protein degradation and assayed MU-calpain activity (p<0.05) with no effect on the activity of calpastatin. beta-Agonist treatment increased hind-limb protein synthesis (p<0.01), calpastatin activity (p<0.1) and decreased (p<0.01) MU-calpain activity, but did not effect protein degradation. Significant correlations were observed between Myofibril Fragmentation Index (MFI) values during post-mortem storage and initial post-slaughter calpastatin activity at days 3 (r=-0.34, p<0.1), 5 (r=-0.58, p<0.01) and 9 (r=-0.58, p<0.1), and MU-calpain activity at days 5 (r=0.35, p<0.1) and 9 (r=0.41, p<0.05). However, stronger correlations were observed between the ratio of MU-calpain to calpastatin, an estimate of potential MU-calpain proteolytic activity, and the rate of myofibril fragmentation (r=0.75, p<0.001) and tenderisation (r=-0.64, p<0.01) during aging. These results are consistent with the calpain system being the major proteolytic system involved in myofibril fragmentation and hence aging related tenderisation of meat. PMID- 22062139 TI - Volatile compounds of dry-cured Iberian ham as affected by the length of the curing process. AB - Volatile compounds from 10 dry-cured Iberian hams ripened for two different processing times, a prolonged traditional one (600 days) and a shortened process (420 days), were analysed by purge and trap coupled to gas chromatography-mass spectroscopy. Eighty-three compounds were identified which agreed with the major classes found in other ham types. The amount of methyl branched alkanes was much higher than in other dry-cured ham types, probably due to the feeding regime. The percentages of 2- and 3-methylbutanal were higher (p<0.0001 and p<0.0003, respectively) in the longer aged hams, whereas the amounts of some compounds from lipid oxidation decreased from 420 to 600 days aging. In agreement with these observations, 600-day hams had higher scores for those odour and flavour traits usually considered to be positive attributes and lower scores for rancidity. A positive and significant correlation between 2-methyl butanal and cured flavour was found. PMID- 22062140 TI - Knife and impact cutting of lamb bone. AB - The forces and hence fracture energies required to cut bone are presented in this paper and the merits of cutting with a high speed blade are considered. A plain knife blade was used to cut cancellous and compact lamb bone using three different methods. A microtome was used to produce a range of cut thicknesses which enabled the fracture energy to be separated into friction, surface fracture and plastic deformation energies. A tensile test machine was used to produce thicker off-cuts so that the energy required to cut through full sections of bone could be determined. A high speed rail gun was used to cut at speeds up to 130 m/s. The energy required to cut bone did not change with blade speed. However, the energies measured during the cutting varied over a wide range. In situations in which the surface of the cut bone exhibited a very uneven surface high energy was required, whereas when the resulting cut surface was planar the cutting energy was low. A light weight blade which impacts the bone at high speed will transmit a small impulse to the carcass which may be absorbed without transmitting strain to the muscle/connective tissue. This may allow the development of a high speed knife which will cut bone without excessively damaging the meat surrounding the cut. PMID- 22062141 TI - Effect of a high linoleic acid diet on lipogenic enzyme activities and on the composition of the lipid fraction of fat and lean tissues in the pig. AB - The aim of this study was to examine the influence of a high linoleic acid diet on lipogenic enzyme activities in pig tissues and on the dietetic quality of these tissues (subcutaneous adipose tissue, Semimembranosus and Diaphragma muscles). Pigs were fed diet M containing 4% of maize oil or diet T containing 4% of tallow from 40 to 100 kg live weight. We did not observe any differences in growth or slaughter performances that could be attributed to diet. Lipogenic enzyme activities were higher in the adipose tissue of pigs fed diet M. However, diet had no effect on lipogenesis in the muscles. The lipid, linoleic acid, and cholesterol contents were higher in the adipose tissue of pigs fed diet M whereas the oleic acid concentration of the adipose tissue was lower. No significant increase in the lipid content of either muscle was however observed in pigs fed diet M. The linoleic acid and cholesterol contents were higher in both muscles of pigs fed diet M than in muscles of pigs fed diet T. PMID- 22062142 TI - Effects of rigor attainment temperature on meat blooming and colour on display. AB - This paper describes the colour properties of seven hot-boned, unstimulated beef striploins during rigor attainment at 9, 14 and 24 degrees C, during blooming at 4 degrees C, and after storage at -1 degrees C for 0, 2 and 8 weeks. Immediately after rigor attainment (0 weeks of storage) full blooming, as judged by L* and chroma, took at least 12 h. After 2 and 8 weeks storage, blooming was complete within about 4 h. The exponential equations describing blooming were different for 0 weeks compared with 2 and 8 weeks. This difference can be explained in terms of oxygen consumption by meat freshly in rigor. At 0 weeks, meat that entered rigor at 24 degrees C had the best bloomed colour, whereas at 2 and 8 weeks the 9 degrees C treatment had the best and the 24 degrees C the worst. The data set, which spanned a range of ultimate pH values and three rigor attainment temperatures, was used to estimate the value of early colour measurements (first 24 h post-rigor) in predicting colour during display several weeks later. As judged by correlation coefficients, early measurements of hue were the only ones useful. L* and chroma were poor predictors. This result, together with the knowledge that blooming is slow in the first 24 h post-rigor, casts doubt on the value of subjective or objective colour assessments made in chillers. Temperature of rigor attainment between 9 and 24 degrees C did not affect the time of browning onset, nor the rate of browning. It was confirmed that meat with lower pH had higher chroma before and after blooming. PMID- 22062143 TI - The effect of RN gene on yields and quality of extended cooked cured hams. AB - The effect of RN(-) allele on minimally processed hams as manufactured in France is now well established. In the present study, meat from 35 rn(+) and 51 RN(-) pigs on the basis of their glycolytic potential (GP) was used to assess the effect of the RN(-) allele on a model system and on yields and quality of cooked hams cured with a 40% brine addition containing the most common meat processing ingredients. Quality parameters were also measured on the fresh loins and a glucose assay was carried out on meat juice from both hams and longissimus dorsi (LD) muscles. With respect to GP, glucose content of LD juice gave the best prediction of RN status with 10% misclassified samples in comparison with 20% as determined from ham juice. Lower pH and higher drip loss and L* values were measured on the LD from RN(-) pigs (p?0.001). Technological yields obtained on the model system and on extended cooked cured hams were lower in meat from RN(-) pigs (p?0.001). However, pH value was more influential on the yield of the model system while protein content and particularly the amount of extractable sarcoplasmic proteins were more determinative on cured hams probably due to the effect of tumbling. All other quality traits were lower in hams from RN(-) pigs (p?0.001). Meat from RN(-) pigs can be used for the manufacture of extended cured products, but under similar processing technologies, quality and yield will remain inferior to what would provide pork of normal quality. PMID- 22062144 TI - Tyramine production by a strain of Carnobacterium divergens inoculated in meat fat mixture. AB - This study determined if a strain of Carnobacterium divergens producing tyramine in laboratory medium is able to produce this amine in meat. Thus the strain was inoculated into a sterile meat-fat mixture of initial pH 5.3 or 4.9 and incubated at 15 degrees C or 25 degrees C. Amine production in these samples was measured at 12 days and compared to that in non-inoculated samples. Non-inoculated samples and those inoculated with C. divergens had the same low content of tryptamine, putrescine, cadaverine, histamine, spermine and spermine. Maximum tyramine and phenylethylamine production was observed in sample of initial pH 5.3 inoculated with C. divergens and incubated at 25 degrees C. The amount of tyramine produced correlated with the growth of the strain, and the amount of lactate and acetate produced. PMID- 22062145 TI - Calpain-calpastatin and toughness in M. longissimus from electrically stimulated lamb and beef carcasses. AB - Shear strength, pH, temperature, MU-calpain, m-calpain and calpastatin levels were measured over a two-week post-slaughter period in Longissimus lumborum et thoracis (LD) from six lamb and six beef carcasses. All carcasses were subjected to high voltage electrical stimulation. The toughness of the beef LD determined by a MIRINZ tenderometer at 24 h post-slaughter showed a strong correlation (r=0.91) with pH of the LD at 3 h. Beef LD toughness at 14 days was correlated (r=0.84) with initial m-calpain levels. In both lamb and beef, LD toughness at 4 and 14 days respectively was also correlated with initial levels of calpastatin (r=0.85, 0.83, respectively). The strong correlation between calpastatin and the rate of tenderisation indicates that the calpain system is closely linked to the proteolytic breakdown of myofibrillar proteins. There is also evidence of an interaction between pH and MU-calpain activity. The MU-calpain, m-calpain, calpastatin, pH and temperature kinetic changes which occurred during the post mortem ageing of beef and lamb LD were applied to a computer program which predicted rate of meat tenderisation by calculating in situ calpain activity. The closeness of fit between the predicted rate of meat tenderisation and the observed tenderness values of beef and lamb LD indicates that the post-mortem activity of MU-calpain is the major determinant of variations in tenderness. However, application of the meat tenderisation predictive program to LD from individual animals revealed that the program was not sufficiently robust for this use. PMID- 22062146 TI - Myoglobin inhibition of most protease activities measured with fluorescent substrates is an artifact! AB - Myoglobin has been suggested to be a potential inhibitor of endogenous muscle proteases as different as cathepsin B, cathepsin L, cathepsin H and calpains all being supposed to be important in post-mortem muscle. The present work aimed at verifying the ability of myoglobin and its prosthetic group, hemin, to inhibit a series of endopeptidases including papain, cathepsin B, trypsin, calpains as well as two activities of the 20S proteasome. The conclusion of the present work was that inhibition of proteolytic activities of endopeptidases by myoglobin is an artifact. This was based on the following evidences: (1) a similar extent of inhibition was observed for all proteases tested whether myoglobin or hemin were added before starting the reaction or after having stopped it; (2) a quenching of the probes fluorescence by myoglobin and hemin; (3) no inhibition of calpains were found when assayed with non labeled casein as substrate and the activity expressed as the increase in the absorbency at 280 nm of the TCA soluble protein fragments.(1). PMID- 22062147 TI - Effect of carnosine, salt and dietary vitamin E on the oxidative stability of chicken meat. AB - The effect of carnosine on lipid and cholesterol oxidation in salted chicken thigh meat and its relationship to dietary alpha-tocopherol supplementation was examined. Broilers (Cobb 500) were fed diets with a basal (30 mg kg(-1)) or supplemental (200 mg kg(-1)) level of alpha-tocopheryl acetate for 6 weeks. Thigh meat patties were prepared with carnosine (1.5%), salt (1%) or salt plus carnosine. Salt accelerated lipid and cholesterol oxidation following cooking and refrigerated storage. However, carnosine inhibited lipid and cholesterol oxidation in salted patties. Dietary alpha-tocopherol supplementation also reduced the extent of lipid and cholesterol oxidation in salted patties. The combination of carnosine and dietary alpha-tocopherol resulted in the greatest lipid and cholesterol stability in salted meat. PMID- 22062148 TI - Effect of dietary vitamin E supplementation on the colour and lipid stability of fresh, frozen and vacuum-packaged beef. AB - The effects of dietary vitamin E supplementation on tissue alpha-tocopherol (alpha-Toc) levels and on the susceptibility of fresh, frozen and vacuum-packaged beef to lipid oxidation and colour deterioration were investigated. Friesian cattle were fed diets containing 20 (basal, n=5) or 2000 (supplemented, n=5) IU (alpha-tocopheryl acetate/kg feed/day for approximately 50 days prior to slaughter. alpha-Toc levels were higher (p<0.05) in muscles from supplemented animals than from those on a basal diet. Significant differences in alpha-Toc levels were also observed between muscles from different treatment groups, the order of the supplemented group was: M. psoas major (PM)>M. longissimus dorsi (LD)>M. gluteus medius (GM) (p<0.05), and in the basal group the order was: PM>GM>LD (p<0.05). Supplemented fresh, frozen and vacuum packed beef showed greater colour and lipid oxidative stability than meat from the basal group after 7 days retail display at 4 degrees C (p<0.05). Thus, dietary (alpha-Toc supplementation appeared to retard metmyoglobin and TBARS formation in LD, GM and PM and increased the colour shelf life of these muscles. PMID- 22062149 TI - Antioxidant activity of mechanically separated pork extracts. AB - Utilization of synthetic carnosine as a food additive is limited by both regulatory and economic hurdles. Therefore, the potential of producing carnosine containing antioxidant extracts from an underutilized skeletal muscle source, mechanically separated pork (MSP), was investigated. Carnosine-containing MSP extracts were capable of inhibiting lipid oxidation both in vitro and in salted ground pork. Heating (60-80 degrees C) the MSP extract removed iron and increased in vitro antioxidant activity. Isolation of a low molecular weight fraction of the MSP extract by ultrafiltration was effective at decreasing iron but did not substantially increase in vitro antioxidant activity. Freeze dried extracts (untreated, 80 degrees C, ultrafiltration permeate) were capable of inhibiting both TBARS and lipid peroxide formation in ground, salted pork stored at -15 degrees C. While MSP extracts were capable of inhibiting lipid oxidation both in vitro and in salted, ground pork, their antioxidant activity was low suggesting that their use as a food additive would be impractical. PMID- 22062150 TI - Effects of muscle alpha-tocopherol level and surface microbiological contamination on retail caselife of fresh beef from the US, Japan and Australia. AB - This study evaluated effects of dietary supplementation of vitamin E (1000 IU vitamin E/daily for 100 days prior to harvest) to fed cattle on retail caselife performance of fresh US beef in an export market (Japan). Economic performance (monetary losses associated with color deterioration) for US beef from vitamin E supplemented cattle vs beef from non-vitamin E supplemented cattle was contrasted. An additional, controlled study was performed to compare muscle alpha tocopherol concentrations, color changes and microbiological growth for fresh beef derived from vitamin E supplemented US cattle and fresh beef from cattle with an unknown history, but from other countries. Australian strip loin steaks had the highest muscle alpha-tocopherol concentrations (4.6 MUg/g tissue), followed by US strip loin steaks derived from vitamin E supplemented cattle (3.4 MUg/g tissue) and Japanese strip loin steaks (2.8 or 2.5 MUg/g tissue). US strip loin steaks from non-vitamin E supplemented cattle had the lowest (p<0.05) alpha tocopherol levels (1.7 MUg/g tissue). Aerobic plate counts and total coliform counts were generally low at 0 days of retail display, and they changed similarly among treatments over 6 days of display, regardless of the country of origin of the beef. Vitamin E supplementation of US cattle reduced total Japanese retail store losses due to discoloration of US beef, in yen, by 5.2 percentage points (p<0.05), saving Japanese retailers US $0.24/kg. Data suggest that US beef normally perceived, in Japan, to discolor more quickly in the retail display case than beef from Australia-would compete more favorably, in shelf-life, with beef from other countries if it was derived from cattle that had been fed supplemental vitamin E. PMID- 22062151 TI - Concentration-response concept in ecotoxicoproteomics: effects of different phenanthrene concentrations to the zebrafish (Danio rerio) embryo proteome. AB - Concentration-response experiments, based on the testing of less replicates in favour of more exposure concentrations, represent the typical design of choice applied in toxicological and ecotoxicological effect assessment studies using traditional endpoints such as lethality. However, to our knowledge this concept has not found implementation in the increasingly applied OMICS techniques studying thousands of molecular endpoints at the same time. The present study is among the first applying the concentration-response concept for an ecotoxicoproteomics study. The effects of six different concentrations in the low effect range (0.1) meat tenderness (Warner-Bratzler shear force) nor sarcomere length of longissimus thoracis muscle. Feeding small amounts of protein supplements to lambs on very low quality forage diets during dry seasons may be a viable path to improve the carcass weight and leanness in lambs without changing the meat tenderness. PMID- 22062174 TI - Effect of pre-slaughter physiological conditions on the oxidative stability of colour and lipid during chill storage of sliced, retail packed roast ham. AB - Pre-slaughter physiological conditions (A serving as control, B subjected to treadmill exercise immediately prior to stunning, C epinephrine injection 15 h prior to slaughter, and D epinephrine injection 15 h prior to slaughter and subjected to treadmill exercise immediately before stunning) were found to significantly affect colour and lipid oxidation of sliced, retail packed roast ham, produced from nitrite-cured (78 ppm nitrite) M. Longissimus dorsi. The pre slaughter treatment resulted in variations in the level of glycogen, lactate, ATP and IMP and pH development as monitored in Longissimus dorsi muscles, with the lowest ultimate pH (pH(u)) in muscles from non-epinephrine treated pigs (treatments A and B). The initial tristimulus L(*)-value and the L(*)-value during chill storage of sliced roast ham packed in laminates with low or with very low oxygen transmission rate (OTR=40 and <0.5 cm(3)/m(2)/atm/24 h, respectively) were significantly affected by treatment, although the effect of the treatments was different during storage for 28 days (interaction between treatment and storage time). Roast ham from treatments A and B generally had a paler appearance (higher L(*)-values) than from treatments C and D. No differences in the initial tristimulus a(*)-values (redness) were found. During chill storage, a pronounced colour fading (decrease in a(*)-values) was seen for laminate with low OTR, with a tendency of better colour stability for treatment C than A, but with no differences for the other treatments. For laminates with very low OTR, the cured meat pigment was stable with no decreases in a(*)-values during storage. Lipid oxidation (thiobarbituric acid reactive substances, TBARS) in products in laminates with low OTR increased during storage and was significantly higher for roast ham from non-epinephrine treated pigs (A and B) than for ham from epinephrine-treated pigs (C and D). Statistical analysis relating pH and the level of glycogen, lactate, creatine phosphate, ATP and IMP in the individual pigs to the product quality parameters revealed that the ultimate level of lactate was the most important single parameter affecting product quality. After 28 days of chill storage, roast ham from pigs subjected to treatments C and D were more likely to support bacterial growth than from treatments A and B. In conclusion, the results show that pre-slaughter physiological conditions are of importance for chemical as well as for microbiological changes in retail stored roast ham. PMID- 22062175 TI - The tenderisation of shin beef using a citrus juice marinade. AB - The effectiveness of organic acids (acetic, citric, lactic) and a citrus juice marinade as tenderising agents in shin beef muscle was investigated. At 0.2 M, citric acid was more effective as a tenderising agent than acetic or lactic acid. Immersion of shin beef strips in citric acid (0-0.05 M) showed that a significant tenderising effect was obtained above a concentration of 0.013 M. When shin beef strips were immersed in the citrus juice marinade (31% orange juice, 31% lemon juice, 38% distilled water) mean pH decreased from 5.7 to 3.1 and mean sample weight increased by ~65%. The mean Warner-Bratzler shear force value decreased from 178 to 44 N cm(-2) following marination while mean sensory analysis scores for tenderness and juiciness increased following marination. A mean total collagen content of 1.4 g/100 g was recorded in shin beef of which 9% was soluble in unmarinated samples and 29% was soluble in marinated samples. The results indicated that the tenderisation of beef samples using a citrus juice marinade could be attributed to marinade uptake by muscle proteins and also to solubilisation of collagen. PMID- 22062176 TI - Optimisation of colour stability of cured ham during packaging and retail display by a multifactorial design. AB - A multifactorial design, including (1) percent residual oxygen, (2) oxygen transmission rate of packaging film (OTR), (3) product to headspace volume ratio, (4) illuminance level and (5) nitrite level during curing, was established to investigate factors affecting light-induced oxidative discoloration of cured ham (packaged in modified atmosphere of 20% carbon dioxide and balanced with nitrogen) during 14 days of chill storage. Univariate statistical analysis found significant effects of all main factors on the redness (tristimulus a-value) of the ham. Subsequently, Response Surface Modelling of the data further proved that the interactions between packaging and storage conditions are important when optimising colour stability. The measured content of oxygen in the headspace was incorporated in the model and the interaction between measured oxygen content in the headspace and the product to headspace volume ratio was found to be crucial. Thus, it is not enough to keep the headspace oxygen level low, if the headspace volume at the same time is large, there will still be sufficient oxygen for colour deteriorating processes to take place. PMID- 22062177 TI - Addition effects of bovine blood globin and sodium caseinate on the quality characteristics of raw and cooked ham pate. AB - The incorporation of 3% globin bovine extracted by the acidified acetone (AG) and carboxymethylcellulose (CG) methods as replacer for sodium caseinate (CA) in ham pate was evaluated. The raw pate batter was evaluated for salt-soluble protein content (SSP), water holding capacity (WHC) and raw batter stability (RBS). The results of CG were similar to those of CA, having both improved two of the three paramaters studied, and AG was the most deleterious, having decreased SSP, WHC and RBS. Only the AG incorporation had unfavorable effects on the cooked ham pate, decreasing the pH and increasing the thiobarbituric acid reactive substances (TBARS) over the storage period (0-45 days). The results suggest CG as the best replacer for CA as the emulsifying agent for ham pate. PMID- 22062178 TI - Physical characteristics of pig fat and their relation to fatty acid composition. AB - One hundred and five samples of pig backfat were assessed for appearance (colour and translucency) and hardness. The fatty acid profile of a selected subset of 50 samples was determined. Increased yellow colour was associated with increased linoleic and alpha-linolenic acid percentages. Increased translucency and fat softness were associated with decreased percentages of palmitic and stearic and oleic acid and a concurrent increase in the proportions of linoleic and alpha linolenic acid. Oleic acid was found to be the single highest component (33.0 45.4%) and linoleic to show the greatest variation in range (9.8-28.4%). PMID- 22062179 TI - Soybean and milk proteins modified by transglutaminase improves chicken sausage texture even at reduced levels of phosphate. AB - Consumer demands for poultry processed meats have increased due to low fat content. In this experiment, chicken sausages were manufactured with various biopolymers prepared from soybean protein, casein, whey protein isolate (WPI), mixtures of soybean protein and casein, and soybean protein and WPI. The extent of various biopolymer formations was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis and high performance liquid chromatography. Cross-linking soybean protein and casein or WPI by transglutaminase provided biopolymers with improved heat stability and emulsifying property. Shear force of chicken sausages were measured to evaluate the addition of biopolymer on the hardness in the presence of 0.05 or 0.2% sodium tripolyphosphate (STPP). The texture of chicken sausages was improved by the addition of such biopolymers even in the presence of 0.05% STPP. These results suggested that chicken sausage texture was improved by the formation of network structures that contribute to hardness of sausage gels with the addition of biopolymers. Thus, addition of biopolymers in the manufacture of chicken sausages may permit reduction in phosphate content without loss in texture. PMID- 22062180 TI - The significance of pre-slaughter stress and diet on colour and colour stability of pork. AB - The influence of pre-slaughter stress and a diet known to affect post mortem muscle metabolism or a standard diet (control pigs) on colour and colour stability of m. longissimus dorsi, m. biceps femoris and m. semimembranosus from 112 female pigs, free of the Halothane gene, was investigated. Pre-slaughter stress increased the early post mortem temperature in the three muscles, as well as the pH decline in control pigs, but not in pigs fed the experimental diet. Colour was measured on sliced samples after 0, 2 and 5 days retail display (1, 3 and 6 days post mortem, respectively) from the three muscles aged 1 day before cutting as well as on sliced m. longissimus dorsi samples aged 8 days before cutting (8, 10 and 13 days post mortem, respectively). Early post mortem pH was not a main determinant of the colour and colour stability, while the degree of pre-slaughter stress and especially its influence on temperature early post mortem was crucial in relation to colour development and colour stability. The discoloration rate was enhanced in m. longissimus dorsi aged for 8 days prior to retail display compared with samples aged for 1 day. However, the extent of the discoloration after 5 days of retail display was not inferior in muscle samples aged for 8 days due to a higher degree of blooming. Finally, present data indicate that 3-4 days ageing of pork prior to retail display results in the optimal colour stability. PMID- 22062181 TI - Descriptive sensory profiling and physical/chemical analyses of warmed-over flavour in pork patties from carriers and non-carriers of the RN(-) allele. AB - Descriptive sensory profiling was carried out to evaluate warmed-over flavour (WOF) development in cooked, chill-stored and reheated pork patties derived from the meat (Musculus longissimus dorsi) of carriers (RN(-)/rn(+)) and non-carriers (rn(+)/rn(+)) of the RN(-) gene. Patties were oven-cooked at 150 and 170 degrees C and chill-stored for up to 5 days to facilitate warmed-over flavour (WOF) development. In addition, thawing losses, cooking losses, pH and TBARS were measured in the cooked pork patties. Analysis of variance (ANOVA) was used to investigate changes in the physical/chemical measurements due to the experimental design variables (storage days, cooking temperature and genotype) and multivariate ANOVA-partial least squares regression (APLSR) was used to determine relationships between the design variables and the sensory and physical/chemical data. WOF was found to involve the development of lipid oxidation derived nuance off-flavour and odour notes, e.g. rancid-like flavour and linseed oil-like odour, in association with a concurrent decrease in 'meatiness' as described by, e.g. cooked pork meat-like flavour. Cooking temperature was described by roasted-like and caramel-like odours and samples from carriers of the RN(-) gene were described as more 'sour' and 'metallic'. Thawing and cooking losses were found to be significantly (P <0.05) higher in meat from carriers of the RN(-) gene versus non-carriers. pH was negatively related to samples from carriers of the RN(-) gene. However, the measured pH in RN(-) carriers could not be significantly ascribed as lower in non-carriers in the freshly cooked meat samples. TBARS were found to be significant (P <0.05) predictors of the sensory terms related to the lipid oxidation aspect of WOF. Moreover, TBARS were significantly (P <0.05) higher in meat from RN(-) gene carriers but, significantly (P <0.05) lower in meat cooked at high oven temperatures (170 degrees C). The former effect was postulated as related to pH and the latter as related to the antioxidant effects of Maillard reaction products developed at higher cooking temperatures. Overall, WOF, cooking temperature and genotype were differentiated as individual dimensions through sensory profiling of the meat samples and each source of variation was characterised by specific groups of sensory descriptors. Moreover, the predictive nature of thawing losses, cooking losses and TBARS was established for the effects of RN(-) gene, cooking temperature and WOF, respectively. PMID- 22062182 TI - Effects of massaging time on texture, rheological properties, and structure of three pork ham muscles. AB - Changes in texture parameters (hardness, cohesiveness, chewiness), rheological properties (elastic and viscous moduli), and structural elements (fibre cross sectional area and thickness of peri- and endomysium) of three pork ham muscles: Biceps femoris (BF), Semimembranosus (SM), and Quadriceps femoris (QM), subjected to effective massaging for 2, 4, 6, 8, 10, 12 h were followed. BF, with its higher fibre cross-sectional area thicker peri- and endomysium, compared with QF and SM, was harder, more elastic, and more viscous than the other two muscles. Massaging resulted in an increase in the mean fibre cross-sectional area, changes in thickness of the peri- and endomysium, and a reduction in hardness and chewiness as well as in elastic and viscous moduli of the muscles studied. The lower were the initial values of textural and structural parameters and rheological properties of a muscle, the shorter massage time was necessary. To arrive at comparable values of textural parameters, rheological properties, and a similar sensory acceptance, BF, SM, and QF had to be effectively massaged for 12, 6, and 4 h, respectively. PMID- 22062183 TI - Fractionation and characterization of edible sheep tail fat. AB - Edible sheep tail fat was effectively fractionated by an acetone crystallization. Each of the fractions and filtrates were analyzed for melting point, refractive index, iodine value, fatty acid composition, and characterized by differential scanning calorimetry. Fatty acid analysis indicated that as the fractionation temperature decreased, the concentration of unsaturated fatty acids in the fractions increased. The liquid fraction had a differential scanning calorimetry melting curve similar to commercial salad oil and the curve of one of the filtrates resembled that of cocoa butter. PMID- 22062184 TI - Porcine oxymyoglobin and lipid oxidation in vitro. AB - The present study was carried out to investigate the effect of dietary alpha tocopherol supplementation on porcine oxymyoglobin (OxyMb) and lipid oxidation (TBARS) in model lipid systems, and to determine the influence of 4 hydroxynonenal (4-HNE), a secondary product of lipid oxidation, on porcine OxyMb stability. Porcine metmyoglobin (MetMb) formation was greater in the presence of 4-HNE than the control (P<0.05). Western blot analyses confirmed the covalent modification of myoglobin (Mb) histidine residues by 4-HNE. When combined with microsomes, both equine and porcine OxyMb oxidation increased with time of incubation, and was greater at 37 than at 25 degrees C (P<0.05). Lower TBARS values were observed in microsomes prepared from vitamin E-supplemented than control pork livers (P<0.05). alpha-Tocopherol concentration did not affect OxyMb oxidation in microsomes at 25 or 37 degrees C (P>0.05). These results differ from those observed with beef muscle microsomes where both OxyMb and lipid oxidation were delayed with elevated alpha-tocopherol levels. These results suggest that the factors affecting Mb and lipid oxidation interactions may be species-dependent. PMID- 22062185 TI - Quality characteristics of irradiated chicken breast rolls from broilers fed different levels of conjugated linoleic acid. AB - Dietary conjugated linoleic acid (CLA) treatment reduced color a*- and b*-values of cooked chicken breast rolls. Sensory panels rated the color of cooked chicken rolls with CLA treatments darker than the control. The production of carbon monoxide (CO) in cooked chicken rolls increased dramatically after irradiation and was correlated with the increased redness of cooked chicken rolls after irradiation. Consumer test indicated that the color of cooked chicken rolls after irradiation was preferred to the nonirradiated, but no preference for the color among the three CLA treatments was found. Irradiation greatly increased volatile production and induced a metallic off-flavor in chicken rolls. Sensory evaluation indicated that the hardness of chicken rolls increased and juiciness decreased as the dietary level of CLA increased. PMID- 22062186 TI - Carcass and meat quality characteristics of the progeny of two swine sire lines reared under differing environmental conditions. AB - The objective of this study was to compare the carcass and meat quality of pigs of two sire lines (A vs B) reared in either a spacious or crowded environment. A total of 128 pigs (barrows and gilts) were used in the study. Animals were slaughtered at 120 kg live weight. Dressing percentage was greater for line A in the spacious but not the crowded environment and line A had a greater loin eye area than line B. Compared to line B, the longissimus from line A had lower pH, higher L* and b* values, and was judged to be paler and softer with a lower marbling fat content. Longissimus L* values were lower for pigs reared in the crowded compared to the spacious environment. Longissimus drip loss was greater for line A compared to line B in the spacious but not the crowded environment. This study highlights genetic differences in pork quality and suggests rearing environment effects that warrant further study. PMID- 22062187 TI - Prediction of pork carcass composition based on cross-sectional region analysis of dual energy X-ray absorptiometry (DXA) scans. AB - Dual energy X-ray absorptiometry (DXA) was used to measure pork carcass composition by performing a total scan of the right half of 262 pork carcasses (42.7+/-5.2 kg). The DXA scans were analyzed for percentage fat in the entire half-carcass as well as the shoulder, ham, loin, and side regions. In addition, a total of 14 cross-sections (57.6 mm wide) were analyzed: six in the shoulder/thoracic region, three in the loin region, and five in the ham region. Relative to the DXA measurement of total fat content, the coefficient of determination (R(2)) for a single cross-sectional slice ranged from 0.908 to 0.976. Relative to chemical analysis, a single slice from the ham region predicted the percentage of fat or lean in the half-carcass with an R(2) of 0.81 and a standard error of the estimate of 2.04. Prediction equations were used to analyze a separate group of 65 half-carcasses. These results indicate that carcass fat and lean percentages can be measured by performing a single-pass cross-sectional scan that would be compatible with on-line processing. PMID- 22062188 TI - Effect of gamma irradiation on the texture and microstructure of chicken breast meat. AB - This study investigated the textural and microstructural properties of chicken breast meat exposed to gamma irradiation ((60)Cobalt) and stored at 4 degrees C. Textural properties of the irradiated (n=27) and unirradiated chicken breasts (control) were determined by measuring shear force and cooking loss at day 0 and at 2-day intervals for a 14-day refrigerated storage period. In addition, microstructural changes of the irradiated and unirradiated chicken breasts were compared. Irradiated chicken breasts had more cooking loss and higher (P<0.0001) shear force than unirradiated chicken breasts. Transmission electron microscopy showed significant differences (P<0.0001) in size of myofibril units (sarcomeres) between irradiated and unirradiated breast. Shrinkage in sarcomere width (myofibril diameter) and disruption of myofibrils in irradiated breast meat were also noticed when compared with unirradiated breast meat. PMID- 22062190 TI - Task-dependent activations of human auditory cortex during spatial discrimination and spatial memory tasks. AB - In the present study, we applied high-resolution functional magnetic resonance imaging (fMRI) of the human auditory cortex (AC) and adjacent areas to compare activations during spatial discrimination and spatial n-back memory tasks that were varied parametrically in difficulty. We found that activations in the anterior superior temporal gyrus (STG) were stronger during spatial discrimination than during spatial memory, while spatial memory was associated with stronger activations in the inferior parietal lobule (IPL). We also found that wide AC areas were strongly deactivated during the spatial memory tasks. The present AC activation patterns associated with spatial discrimination and spatial memory tasks were highly similar to those obtained in our previous study comparing AC activations during pitch discrimination and pitch memory (Rinne et al., 2009). Together our previous and present results indicate that discrimination and memory tasks activate anterior and posterior AC areas differently and that this anterior-posterior division is present both when these tasks are performed on spatially invariant (pitch discrimination vs. memory) or spatially varying (spatial discrimination vs. memory) sounds. These results also further strengthen the view that activations of human AC cannot be explained only by stimulus-level parameters (e.g., spatial vs. nonspatial stimuli) but that the activations observed with fMRI are strongly dependent on the characteristics of the behavioral task. Thus, our results suggest that in order to understand the functional structure of AC a more systematic investigation of task-related factors affecting AC activations is needed. PMID- 22062191 TI - Autism spectrum traits predict the neural response to eye gaze in typical individuals. AB - Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterised by impaired social interaction and communication, restricted interests and repetitive behaviours. The severity of these characteristics are posited to lie on a continuum extending into the typical population, and typical adults' performance on behavioural tasks that are impaired in ASD is correlated with the extent to which they display autistic traits (as measured by Autism Spectrum Quotient, AQ). Individuals with ASD also show structural and functional differences in brain regions involved in social perception. Here we show that variation in AQ in typically developing individuals is associated with altered brain activity in the neural circuit for social attention perception while viewing others' eye gaze. In an fMRI experiment, participants viewed faces looking at variable or constant directions. In control conditions, only the eye region was presented or the heads were shown with eyes closed but oriented at variable or constant directions. The response to faces with variable vs. constant eye gaze direction was associated with AQ scores in a number of regions (posterior superior temporal sulcus, intraparietal sulcus, temporoparietal junction, amygdala, and MT/V5) of the brain network for social attention perception. No such effect was observed for heads with eyes closed or when only the eyes were presented. The results demonstrate a relationship between neurophysiology and autism spectrum traits in the typical (non-ASD) population and suggest that changes in the functioning of the neural circuit for social attention perception is associated with an extended autism spectrum in the typical population. PMID- 22062192 TI - Cortical cartography and Caret software. AB - Caret software is widely used for analyzing and visualizing many types of fMRI data, often in conjunction with experimental data from other modalities. This article places Caret's development in a historical context that spans three decades of brain mapping--from the early days of manually generated flat maps to the nascent field of human connectomics. It also highlights some of Caret's distinctive capabilities. This includes the ease of visualizing data on surfaces and/or volumes and on atlases as well as individual subjects. Caret can display many types of experimental data using various combinations of overlays (e.g., fMRI activation maps, cortical parcellations, areal boundaries), and it has other features that facilitate the analysis and visualization of complex neuroimaging datasets. PMID- 22062193 TI - Race modulates neural activity during imitation. AB - Imitation plays a central role in the acquisition of culture. People preferentially imitate others who are self-similar, prestigious or successful. Because race can indicate a person's self-similarity or status, race influences whom people imitate. Prior studies of the neural underpinnings of imitation have not considered the effects of race. Here we measured neural activity with fMRI while European American participants imitated meaningless gestures performed by actors of their own race, and two racial outgroups, African American, and Chinese American. Participants also passively observed the actions of these actors and their portraits. Frontal, parietal and occipital areas were differentially activated while participants imitated actors of different races. More activity was present when imitating African Americans than the other racial groups, perhaps reflecting participants' reported lack of experience with and negative attitudes towards this group, or the group's lower perceived social status. This pattern of neural activity was not found when participants passively observed the gestures of the actors or simply looked at their faces. Instead, during face viewing neural responses were overall greater for own-race individuals, consistent with prior race perception studies not involving imitation. Our findings represent a first step in elucidating neural mechanisms involved in cultural learning, a process that influences almost every aspect of our lives but has thus far received little neuroscientific study. PMID- 22062194 TI - Multiple white matter tract abnormalities underlie cognitive impairment in RRMS. AB - Diffusion tensor imaging (DTI) is a sensitive tool for detecting microstructural tissue damage in vivo. In this study, we investigated DTI abnormalities in individuals with relapsing remitting multiple sclerosis (RRMS) and examined the relations between imaging-based measures of white matter injury and cognitive impairment. DTI-derived metrics using tract-based spatial statistics (TBSS) were compared between 37 individuals with RRMS and 20 healthy controls. Cognitive impairment was assessed with three standard tests: the Symbol Digit Modalities Test (SDMT), which measures cognitive processing speed and visual working memory, the Rey Auditory Verbal Learning Test (RAVLT), which examines verbal memory, and the Paced Auditory Serial Addition Test (PASAT), which assesses sustained attention and working memory. Correlations between DTI-metrics and cognition were explored in regions demonstrating significant differences between the RRMS patients and the control group. Lower fractional anisotropy (FA) was found in RRMS participants compared to controls across the tract skeleton (0.40 +/- 0.03 vs. 0.43 +/- 0.01, p<0.01). In areas of reduced FA, mean diffusivity was increased and was dominated by increased radial diffusivity with no significant change in axial diffusivity, an indication of the role of damage to CNS myelin in MS pathology. In the RRMS group, voxelwise correlations were found between FA reduction and cognitive impairment in cognitively-relevant tracts, predominantly in the posterior thalamic radiation, the sagittal stratum, and the corpus callosum; the strongest correlations were with SDMT measures, with contributions to these associations from both lesion and normal-appearing white matter. Moreover, results using threshold-free cluster enhancement (TFCE) showed more widespread white matter involvement compared to cluster-based thresholding. These findings indicate the important role for DTI in delineating mechanisms underlying MS-associated cognitive impairment and suggest that DTI could play a critical role in monitoring the clinical and cognitive effects of the disease. PMID- 22062195 TI - Natural history of end-stage LV dysfunction: has it improved from the classic Franciosa and Cohn Graph? AB - The pathophysiology of heart failure is complex, and downstream effects cause decline in multiple systems. Medical therapies intended to slow or reverse disease progression have been shown to improve prognosis in prospective trials. Improvement in prognosis has also been observed in large cohorts across time strata. However, near-term mortality for those with advanced disease remains unacceptably high. Prognosis in advanced heart failure may be assessed with the appropriate use of clinical prediction tools. Optimal timing of evaluation for heart transplantation and/or mechanical circulatory support depends on an understanding of these issues. PMID- 22062196 TI - Editorial comment on "Natural history of end-stage LV Dysfunction: has it improved from the classic Franciosa and Cohn Graph?". PMID- 22062197 TI - Current technology: devices available for destination therapy. AB - Left ventricular assist device therapy as a destination therapy for end-stage heart failure has made a large leap with continuous flow devices. Continuous flow does not seem to have a detrimental effect on end-organ function, at least in the midterm. Various expected and unexpected complications have been reported associated with this technology. More experience and research are warranted. PMID- 22062198 TI - Editorial comments on "Current technology-devices available for 'destination' therapy". PMID- 22062199 TI - Avoiding technical pitfalls in left ventricular assist device placement. AB - Left ventricular assist device (LVAD) placement is a serious surgical procedure. At our center, we accumulated a very large experience with the Novacor LVAD from the very first clinical trial, as well as from more recent experiences with the Jarvik 2000 and the HeartMate II. This article discusses technical issues that are common to all durable LVAD devices, with special emphasis on strategy and technical considerations aimed at avoiding surgical pitfalls. PMID- 22062200 TI - Left ventricular assist device driveline infections. AB - This article reviews some important aspects of driveline infection in patients under left ventricular assist device (LVAD) support, including epidemiology, causes, diagnosis, and treatment options, both medical and surgical. Focus is placed on prevention along every aspect of the process of LVAD therapy, as the authors believe this is the most efficient measure to fight driveline infections. Once driveline infection is present, early recognition and adequate treatment, including surgical measures, play a central role management, and are key to achieving the goals of LVAD support. PMID- 22062201 TI - Editorial comments on "left-ventricular assist device driveline infections". PMID- 22062202 TI - Bridge to recovery: what remains to be discovered? AB - The use of left ventricular assist devices to induce substantial myocardial recovery with explantation of the device, bridge to recovery (BTR), is an exciting but currently grossly underused application. Recently acquired knowledge relating to BTR and its mechanisms offers unprecedented opportunities to streamline its use and unravel some of the secrets of heart failure with much wider implications. This article reviews the status, challenges, and future of cardiac recovery. PMID- 22062203 TI - Editorial comment on "bridge to recovery: what remains to be discovered?". PMID- 22062204 TI - Tips on tuning each device: technical pearls. AB - Although the basic technique is relatively similar among the currently available left ventricular assist devices (LVAD), there are many subtle potential technical pitfalls for each device that could result in grave adverse events. In this article, the technical perils of the principal implantation technique and LVAD related concomitant surgical procedures as well as of the implantation technique specific to currently available implantable LVADs, including HeartMate XVE, HeartMate II, HeartWare, and DuraHeart, are described. PMID- 22062205 TI - Editorial comments on "tips on 'tuning' each device-technical pearls". PMID- 22062207 TI - Editorial comments on "the future of adult cardiac assist devices: novel systems and mechanical circulatory support strategies". PMID- 22062206 TI - The future of adult cardiac assist devices: novel systems and mechanical circulatory support strategies. AB - The recent, widespread success of mechanical circulatory support has prompted the development of numerous implantable devices to treat advanced heart failure. It is important to raise awareness of novel device systems, the mechanisms by which they function, and implications for patient management. This article discusses devices that are being developed or are in clinical trials. Devices are categorized as standard full support, less-invasive full support, partial support: rotary pumps, partial support: counterpulsation devices, right ventricular assist device, and total artificial heart. Implantation strategy, mechanism of action, durability, efficacy, hemocompatibility, and human factors are considered. The feasibility of novel strategies for unloading the failing heart is examined. PMID- 22062208 TI - Transplant or VAD? AB - Major advances in vascular assist device (VAD) technology and the clinical acceptance of destination therapy for patients with contraindications to transplant raise the questions of what patient benefit is necessary to recommend VAD implant for long-term support in patients who are transplant candidates. What are the appropriate indications for use and timing considerations for long-term VAD therapy in patients who qualify for transplant but are unlikely to obtain a donor? The authors suggest that VAD implantation for the indication of "maintenance therapy" where patients must remain on the VAD for two years before becoming transplant eligible, would constitute an appropriate clinical avenue to study these issues. PMID- 22062209 TI - Editorial comments on "VAD or transplant". PMID- 22062210 TI - Who needs an RVAD in addition to an LVAD? AB - Mechanical circulatory support using left ventricular assist devices (LVAD) has become an accepted mode of therapy for both bridging patients with end-stage heart failure to transplant and as a destination therapy. Right ventricular (RV) dysfunction is common after LVAD insertion and is a significant source of morbidity and mortality in patients undergoing LVAD placement. Several studies have identified clinical, laboratory, hemodynamic, and echocardiographic parameters that may serve as risk factors for RV dysfunction after LVAD placement. Furthermore, scoring systems have been established to help quantitatively predict the potential need for RV support after LVAD placement. PMID- 22062211 TI - Editorial comments on "who needs an RVAD in addition to an LVAD?". PMID- 22062212 TI - Toward total implantability using free-range resonant electrical energy delivery system: achieving untethered ventricular assist device operation over large distances. AB - Heart failure is a terminal disease with a very poor prognosis. Although the gold standard of treatment remains heart transplant, only a minority of patients can benefit from transplants. Another promising alternative is mechanical circulatory assistance using ventricular assist devices. The authors envision a completely implantable cardiac assist system affording tether-free mobility in an unrestricted space powered wirelessly by the innovative Free-Range Resonant Electrical Energy Device (FREE-D) system. Patients will have no power drivelines traversing the skin, and this system will allow power to be delivered over room distances and will eliminate trouble-prone wirings, bulky consoles, and replaceable batteries. PMID- 22062213 TI - Editorial comments on "towards total implantability using FREE-D system: achieving un-tethered VAD operation over large distances". PMID- 22062214 TI - Right ventricular dysfunction in patients undergoing left ventricular assist device implantation: predictors, management, and device utilization. AB - Nonreversible failure of the right ventricle is seen in 0.04% to 0.1% of postcardiotomy cases. The incidence of right ventricular dysfunction after left ventricular assist device (LVAD) implantation that fails to resolve in the operating room is reported to be as frequent as 20% to 50% and imposes a considerable burden in terms of postoperative morbidity and mortality. Should this syndrome supervene, the mortality of an LVAD operation increases from 19% to 43%. Although most patients can be maintained with prolonged inotropic support, 10% to 15% may require implantation of a separate right ventricular support device. PMID- 22062215 TI - Editors' comments on "right ventricular dysfunction in patients undergoing left ventricular assist device implantation: predictors, management and device utilization". PMID- 22062216 TI - Can the occurrence of gastrointestinal bleeding in nonpulsatile left ventricular assist device patients provide clues for the reversal of arteriosclerosis? AB - This article is written not only to explore the deleterious effects of nonpulsatile flow (namely, gastrointestinal [GI] bleeding), but also to propose the novel concept that deliberate induction of nonpulsatile flow might be harnessed to produce beneficial remodeling in arteriosclerotic arteries. Continuous-flow left ventricular assist devices have proven their efficacy in the treatment of end-stage heart disease. They are a reliable option in bridge-to transplant and destination therapy. An enigmatic consequence of this therapy has been occult GI bleeding. PMID- 22062217 TI - Editorial comment on "can the occurrence of gi bleeding in non-pulsatile LVAD patients provide clues for the reversal of arteriosclerosis?". PMID- 22062219 TI - Left ventricular assist devices. Preface. PMID- 22062220 TI - TLR4 activity is required in the resolution of pulmonary inflammation and fibrosis after acute and chronic lung injury. AB - Pulmonary fibrosis is an inflammation-driven lung disease with a poor prognosis and no cure. Here we report that basal toll-like receptor 4 (TLR4) activity is critical for the resolution of acute and chronic inflammation and pulmonary fibrosis in mouse models of lung injury. We found that genetic or pharmacologic inhibition of TLR4 exacerbates bleomycin-induced pulmonary inflammation, fibrosis, dysfunction, and animal death through promoting formation of an immunosuppressive tissue microenvironment and attenuating autophagy-associated degradation of collagen and cell death in the fibrotic lung tissues. In contrast, pharmacologic activation of TLR4 resulted in a quick resolution of acute inflammation, reversed the established pulmonary fibrosis, improved lung function, and rescued mice from death. Similarly, blocking TLR4 impaired the resolution of silica-induced chronic inflammation and fibrosis. Importantly, altering autophagic activity could reverse the TLR4-regulated lung inflammation, fibrosis, dysfunction, and animal death. Rapamycin, an autophagy activator, reversed the effects of TLR4 antagonism. In contrast, inhibition of autophagy by 3-methyladenine reversed the proresolving and antifibrotic roles of TLR4 agonists and increased animal death. These results not only highlight a pivotal role for TLR4-mediated basal immunity, particularly autophagic activity, in the proresolution of inflammation and fibrosis after chemical-induced lung injury but also provide proof for the concept for activating TLR4 signaling, particularly TLR4-mediated autophagy, as a novel therapeutic strategy against chronic fibroproliferative diseases that are unresponsive to current therapy. PMID- 22062221 TI - Notch-induced hIL-6 production facilitates the maintenance of self-renewal of hCD34+ cord blood cells through the activation of Jak-PI3K-STAT3 pathway. AB - Ex vivo expansion of CD34(+) stem cells in contact culture between hCD34(+)CD38( )Lin(-) cord blood stem cells and human delta-like-expressing AFT024 feeder cells revealed increased amounts of stemness-related proteins such as HoxB4, GATA2, Bmi 1, and p21 and anti-apoptotic proteins such as Bcl-2, Bcl-xL, Mcl-1, and phospho Bad, when compared with control or noncontact culture. Production of human IL-6 (hIL-6) was markedly elevated in the culture, but was profoundly inhibited by treatment with gamma-secretase inhibitor. In addition, Notch-induced activation of STAT3 was directly involved in gene expression of hIL-6 and soluble hIL 6Ralpha, indicating the close linkage between Notch signaling and hIL-6 production. Furthermore, depletion of soluble hIL-6 (with hIL-6-specific antibodies) and inhibition of IL-6-mediated signals (with a Jak1 inhibitor and wortmannin) severely affected the maintenance of self-renewal of hCD34(+) cord blood cells. It was also observed that the ex vivo expanded CD34(+) cord blood cells were induced to reconstitute human immune cells in nonobese diabetic mice with severe combined immunodeficiency when compared with freshly isolated CD34(+) cord blood cells. Together, these results strongly demonstrate that Notch signaling in the "cell-to-cell contact" between hCD34(+) cord blood and delta like-expressing AFT024 feeder cells facilitates maintenance of self-renewal of hCD34(+) cord blood cells through direct regulation of hIL-6 production. PMID- 22062222 TI - Blockade of interleukin-6 receptor alleviates disease in mouse model of scleroderma. AB - Activation of fibroblasts by interleukin-6 (IL-6) is implicated in the pathogenesis of scleroderma, suggesting that the inhibition of fibroblast activation may be a promising scleroderma treatment. In this study, we used an IL 6 blocking antibody (Ab) and Il-6 knockout (Il-6KO) mice to examine the role of IL-6 in the bleomycin (BLM)-induced mouse model of scleroderma. BLM was administered to C57BL/6 and Il-6KO mice to induce dermal sclerosis. BLM-treated and control phosphate-buffered saline-treated mice were treated with anti-mouse IL-6 receptor monoclonal Ab (MR16-1). Disease severity was evaluated by measuring dermal thickness and skin hardness, by counting the numbers of alpha-smooth muscle actin-positive cells and mast cells, and by examining the cutaneous draining lymph nodes. C57BL/6 mice with BLM induced scleroderma had elevated serum IL-6 levels and more severe dermal sclerosis than Il-6KO mice. Weekly administration of MR16-1, but not control Ab, prevented and improved dermal sclerosis, and also attenuated swelling of the draining lymph nodes. MR16-1 suppressed alpha-smooth muscle actin induction in IL-6-stimulated Il-6KO fibroblasts. Our results indicate that IL-6 contributes to BLM induced dermal sclerosis and that IL-6 receptor-specific monoclonal Ab may improve the symptoms of scleroderma by suppressing fibroblast activation. PMID- 22062223 TI - Characteristics of generalized anxiety disorder in patients with dementia. AB - BACKGROUND: Overlap of cognitive and anxiety symptoms (i.e., difficulty concentrating, fatigue, restlessness) contributes to inconsistent, complicated assessment of generalized anxiety disorder (GAD) in persons with dementia. METHODS: Anxious dementia patients completed a psychiatric interview, the Penn State Worry Questionnaire-Abbreviated, and the Rating for Anxiety in Dementia scale. Analyses to describe the 43 patients with and without GAD included the Wilcoxon Mann-Whitney two-sample test, Fisher's exact test. Predictors of GAD diagnosis were identified using logistic regression. RESULTS: Those with GAD were more likely to be male, have less severe dementia and endorsed more worry, and anxiety compared to patients without GAD. Gender, muscle tension and fatigue differentiated those with GAD from those without GAD. CONCLUSIONS: Although this study is limited by a small sample, it describes clinical characteristics of GAD in dementia, highlighting the importance of muscle tension and fatigue in recognizing GAD in persons with dementia. PMID- 22062224 TI - Effect of dietary tocopherols and tocotrienols on the antioxidant status and lipid stability of chicken. AB - We determined the effect of dietary tocopherols and tocotrienols on the lipid stability of pre-cooked chicken breast and thigh. The birds were supplemented with one of two doses of a commercial mixture of tocopherols and tocotrienols (Oryza1, Oryza2) or one of two doses of all-rac alpha-tocopherol acetate (Toc1, Toc2). Diets were formulated so that Oryza1 and Toc1 and Oryza2 and Toc2 contained similar tocopherol concentrations. No quantifiable amounts of tocotrienols were found in either breast or thigh muscles. Tocotrienols present in the diet reduced muscle alpha-tocopherol concentration. The effect of Oryza1 on the tocopherol content in muscle and on its lipid stability was not significant. The Oryza2, Toc1 and Toc2 diets increased the alpha- and gamma tocopherol in breast and thigh muscles and enhanced their lipid stability. This improvement was only due to the antioxidant action of the tocopherols. Lipid stability of pre-cooked chicken was not enhanced by adding tocotrienols to a tocopherol supplement. PMID- 22062225 TI - Effect of leek and onion on processing and quality characteristics of Greek traditional sausages. AB - The objective of this study was to investigate the effect of leek and onion on processing and quality characteristics of sausages and select the most appropriate, to determine the optimum level of selected vegetable and to improve its effectiveness on quality characteristics of sausages, in comparison to the addition of nitrites (100 ppm), by using a starter culture of Staphylococcus carnosus and ascorbate. The nitrate content of leek ranged from 213 to 255 ppm and that of onion was 79 ppm. Sausages produced with leek had higher (p<0.05) nitrite content (1.3-2.1 ppm) and a (*)(+) values and higher scores for sensory attributes than sausages with onion. Sausages made with the total leek plant had the highest score for overall acceptability. The higher the leek level the higher the nitrate and nitrite content of sausages and the lower the redness, a (*)(+). Sausages with 240 g of leek/kg had the highest (p<0.05) overall acceptability. Sausages with higher leek level had an intensive wrinkling on the surface and also an intensive and undesirable green colour. Sausages produced with 240 g of leek/kg had the same low level of nitrate and nitrite content, higher weight losses and lower pH values after the 3rd day of storage, compared to sausages produced with the addition of sodium nitrite. The addition of starter culture and ascorbic acid improved the redness (a (*)) of sausages and reduced the 2 thiobarbituric acid value. Sausages with leek, starter culture and ascorbic acid had the highest score for odour and taste and overall acceptability. PMID- 22062226 TI - Dielectric and thermophysical properties of meat batters over a temperature range of 5-85 degrees C. AB - Dielectric (dielectric constant (epsilon(')) and loss factor (epsilon")) and thermal (heat capacity (c), thermal conductivity (k) and thermal diffusivity (alpha))) properties of two meat batters (pork luncheon roll (PLR) and white pudding (WP)) were measured between 5 and 85 degrees C. Radio frequency (RF) and microwave (MW) epsilon" values varied across 5-85 degrees C (P<0.05). MW epsilon(') and epsilon" values for WP tended to peak at 45 degrees C and decrease thereafter, whereas for PLR, epsilon(') and epsilon" peaked at 65 degrees C which appeared to match potato starch gelatinisation within this product. WP and PLR had significantly higher c values at 25 degrees C, which corresponded to the MP of pork fat. For PLR, an additional c peak was noted at 65 degrees C, which appeared to correspond to potato starch gelatinisation. At 85 degrees C, k values were higher (P<0.05) than at 5, 25 and 45 degrees C but were not higher than values at 65 degrees C. alpha values increased with temperature (P<0.05). PMID- 22062227 TI - Oxidative stability of frozen pork patties: Effect of fluctuating temperature on lipid oxidation. AB - The mobility of solutes in fat from pork belly, in lean pork belly and in lean pork longissimus dorsi, containing 1% NaCl was characterized by the ESR spin probe technique using the nitroxyl spin probes TEMPO and TEMPOL. The mobility of TEMPO in fat increased for temperature above -60 degrees C and the mobility of TEMPOL in lean meat increased for temperature above -40 degrees C. Temperatures for studying the effect of fluctuating temperatures during frozen storage of meat were selected based on the ESR characterization of the mobility of solutes. The oxidative stability of pork patties during frozen storage was measured as thiobarbituric acid reactive substances (TBARS), during storage at -10, -23 and 40 degrees C and with fluctuations between these temperatures, of pork patties made from pork loin (low fat 1.8%) or pork belly (high fat 22.7%). Lower storage temperatures resulted in less lipid oxidation, and temperature fluctuations between -40 and -23 degrees C and fluctuations between -23 and -10 degrees C resulted in oxidation intermediate to oxidation in samples stored at constant low or high temperatures of the fluctuation interval. The level of alpha-tocopherol was unaffected by the extent of oxidation in the frozen samples, an observation which is discussed in relation to differences in molecular mobility between oxygen and alpha-tocopherol. PMID- 22062228 TI - Effect of ascorbate, nitrate and nitrite on the amount of flavour compounds produced from leucine by Staphylococcus xylosus and Staphylococcus carnosus. AB - Resting cells of Staphylococcus xylosus and S. carnosus were incubated with ascorbate, nitrate and nitrite in defined reaction medium and their degradation of (3)H-labelled leucine into methyl-branched catabolites were studied using HPLC/radiometric detection. The experiments were carried out with and without addition of alpha-ketoglutarate. The main catabolic product of leucine degradation was 3-methylbutanoic acid but also small amounts of alpha-hydroxy isocaproic acid were produced. Nitrite addition lowered the concentration of 3 methylbutanoic acid for both Staphylococcus species and this effect was strongly amplified by ascorbate for S. xylosus but not for S. carnosus. For both species ascorbate alone had little if any effect. Also nitrate lowered the concentration of 3-methylbutanoic acid for S. xylosus. The concentration of alpha-hydroxy isocaproic acid was, however, increased by addition of nitrite and nitrate for S. xylosus. Addition of alpha-ketoglutarate generally increased the concentration of 3-methylbutanoic acid for both S. xylosus and S. carnosus. PMID- 22062229 TI - Cooking temperature effects on the forms of iron and levels of several other compounds in beef semitendinosus muscle. AB - The influence of final cooked temperature on the form of iron present and on the concentration of taurine, carnosine, coenzyme Q(10) and creatine was investigated in surface and inner parts of 30-mm thick steaks from beef semitendinosus muscle (n=6). The use of a fast, dry-heat cooking method with a Silex clam cooker (set at 200 degrees C) led to cooking times ranging from 5.6 to 8.6 min for final internal temperatures of 60 and 85 degrees C, respectively. The proportion of iron as soluble haem iron decreased from 65% in uncooked meat to 22% when cooked to 60 degrees C and then decreased more gradually with increases in final cooked temperature. The proportion of insoluble haem iron increased in a reciprocal manner, while changes in the proportions of soluble and insoluble non-haem iron were relatively small, but increases in the percentage of insoluble non-haem iron with increasing final temperature were significant (P<0.01). Changes in the forms of iron with cooking generally took place more rapidly in surface samples than inner samples. On a dry-matter basis, concentrations of taurine, carnosine, coenzyme Q(10), and creatine all decreased with cooking, but the decreases were greatest for taurine and creatine. Losses of creatine were at least partly due to conversion to creatinine, and, along with the other compounds, probably included some loss in cooking juices. It is concluded that despite these changes with cooking, beef semitendinosus muscle remains a good source of iron and a useful source of the potentially bioactive compounds taurine, carnosine, coenzyme Q(10) and creatine. PMID- 22062230 TI - Accelerated chilling and modified atmosphere packaging affect colour and colour stability of injection-enhanced beef round muscles. AB - Beef knuckles were partially hot-boned within 1.5 h postmortem. Biceps femoris (BF), semimembranosus (SM), vastus lateralis (VL), and rectus femoris (RF) muscles were injection enhanced at 6% (experiment 1) or 10% (experiment 2) of non injected weight and packaged in a high- (HiOx; 80% oxygen and 20% carbon dioxide) or ultra-low oxygen (LoOx; 80% nitrogen and 20% carbon dioxide) modified atmosphere. Hot boning accelerated chilling in all beef round muscles investigated. This resulted in a darker initial beef colour and darker visual colour during display for the BF, RF, and VL, as well as more uniform BF and knuckle steak colour. RF and VL, in experiments 1 and 2, respectively, had the most improved colour and colour stability. Steaks in HiOx MAP had longer colour life in display than steaks that had been in LoOx. Partially removing the beef knuckle early postmortem is a practical process that will improve colour and colour stability of beef round muscles. PMID- 22062231 TI - Evaluation of low-fat sausage containing desinewed lamb and konjac gel. AB - Ground (GR) or desinewed (DS) lamb trimmings were combined with a konjac flour (KF) gel (0%, 10% or 20%) to produce a low-fat (8%) cured sausage. Physiochemical, sensory and shelf-life analyses were performed to determine the efficacy of the fat mimetic. Desinewing reduced collagen content (2.3 mg/g tissue) and cook yield (0.6%) when compared to GR trimmings. Grinding increased aerobic plate counts (APCs) ~0.4log(10)/cm(2) more than DS, but APCs were not affected by inclusion of KF. Sausages with 20% KF lowered cook yield ~1% and slightly reduced sensory panel and texture profile analysis texture values. KF gel incorporated at 10% had similar properties to a control low-fat desinewed lamb sausage, while KF at 20% could reduce "toughening" in low-fat sausage products. Use of konjac gel as a fat mimetic could reduce total caloric energy by replacing a portion of the meat in a sausage formulation. PMID- 22062232 TI - Dual-energy X-ray absorptiometry of the pig: Protocol development and evaluation. AB - As part of a prospective study in bone mineralisation in adult pigs it was necessary to establish guidelines and to define sites for bone mineral measurements. Particular requirements were that, the protocol should be suitable for a mass screening programme in both postmortem specimens and in live animals, and should deliver results of known reliability. Estimates of bone mineral content (BMC) and bone mineral density (BMD) in areas within the 4th metacarpal bone yielded coefficients of variation (CV) in the order of 7% for both regions and estimates in regions which included the entire metacarpal-phalangeal area yielded CV values in the order of 0.7% and 0.6% for BMC and BMD, respectively. A region of interest taken from the coccygeal vertebrae yielded coefficient of variation values of 3% and 2% for BMC and BMD, respectively. Accuracy of dual energy X-ray absorptiometry (DXA) was estimated using a standard curve derived from BMC determined by ashing. There was a high correlation between mineral content determined by DXA and by ashing (R(2)=0.99, p<0.0001). The results suggest that the regions used in this study are suitable for use in large, mass screening, prospective studies. PMID- 22062233 TI - Beef longissimus lumborum, biceps femoris, and deep pectoralis Warner-Bratzler shear force is affected differently by endpoint temperature, cooking method, and USDA quality grade. AB - Effects of endpoint temperature, cooking method, and quality grade on Warner Bratzler shear force (WBSF) of beef longissimus lumborum (LL), biceps femoris (BF), and deep pectoralis (DP) muscles were evaluated. Eighteen of all three subprimals were selected from USDA Select and 18 from USDA Choice (Certified Angus Beef) carcasses for the respective muscles. Muscles were vacuum packaged and held at 1 degrees C for 14 days, frozen (-29 degrees C), sawed into 2.54-cm thick steaks, vacuum packaged, and stored frozen until cooking. Thawed steaks were cooked by either a Magikitch'n((r)) electric belt-grill (BG) at 93 degrees C, or a water-bath at 93 degrees C, to one of nine endpoint temperatures: 40, 45, 50, 55, 60, 65, 70, 75, or 80 degrees C. Belt-grill cooking was much faster and resulted in distinctly less cooking loss than water-bath cooking. Water-bath cooking resulted in higher (P<0.0001) Instron((r)) WBSF (31.92 N) than BG (28.25 N) for LL. The combination of Select quality grade and higher endpoint temperatures resulted in higher (P<0.05) WBSF for LL. Two distinct phases of tenderization/toughening occurred for BF. Between 40 and 60 degrees C, WBSF decreased from 43.95 to 38.16 N (P<0.01), whereas between 60 and 70 degrees C, WBSF increased from 38.16 N to 44.44 N (P<0.05). Water-bath cooling resulted in higher (P=0.0001) DP WBSF (71.12 N) than BG (59.25 N). The DP had a distinct (P<0.0001) decline in WBSF between 45 and 65 degrees C, irrespective of the cooking method, followed by an increase between 65 and 80 degrees C (P<0.01). PMID- 22062234 TI - Functionality of myofibrillar proteins as affected by pH, ionic strength and heat treatment - a low-field NMR study. AB - Myofibrills were extracted from porcine muscle, and their water properties were characterized using low-field nuclear magnetic resonance (NMR) T(2) relaxometry. A T(2) relaxation pattern very similar to the pattern observed in intact meat and water contents comparable to the water content in meat were observed, implying that the myofibrillar structures are responsible for retaining the majority of water in meat. The effect of pH and ionic strength in the samples was investigated as pH was adjusted to 5.4, 6.2, and 7.0 and ionic strength to 0.29, 0.46 and 0.71 M, respectively. Even though there were interactions between pH and ionic strength, the water content in the samples increased significantly with increasing pH and ionic strength. Moreover, mean T(2) relaxation times likewise increased with increasing pH and ionic strength, which reveals that the increased water retention could be ascribed to a swelling of the myofibrils and thereby increased spacing between filaments. The present study demonstrates that NMR T(2) relaxometry is a potential tool to explore how processing factors such as pH and ionic strength affect the microstructure of meat. PMID- 22062235 TI - Effect of radio frequency cooking on the texture, colour and sensory properties of a large diameter comminuted meat product. AB - Radio frequency (RF) cooking is a form of dielectric heating similar to microwave heating. In this study an optimised cooking protocol was developed for pasteurising 1 kg cased meat emulsion samples, which were immersed in 80 degrees C circulating water during cooking. Subsequently, selected quality attributes of RF pasteurised samples were compared to steam pasteurised samples, by instrumental and sensory methods. Instrumental assessments show that RF heated meat batters had a greater ability to hold water, were significantly harder, chewier and gummier (P<0.001), while having less cook colour development than their steam cooked counterparts. Differences were also detected by sensory methods. In conclusion, while differences were detected, it is possible that these could be eliminated by adjusting the cooking protocol to produce similar cook values in RF samples to those in products cooked by steam. PMID- 22062236 TI - Citrus pulp as an ingredient in ostrich diet: effects on meat quality. AB - The purpose of this trial was to study the effects of citrus pulp inclusion in ostrich diets on meat quality, evaluated on iliofibularis and gastrocnemius muscles. M. iliofibularis had a lower ultimate pH (P<0.05) and was lighter in colour (P<0.05) than M. gastrocnemius. The latter had higher moisture (P<0.05) and lower crude protein contents (P<0.05) as compared to M. iliofibularis. M. gastrocnemius had a lower proportion of C14:0 (P<0.05), C16:0 (P<0.05) and C16:1 (P<0.05) and a higher percentage of C18:0 (P<0.05), C20:2omega6 (P<0.05), C20:4omega6 (P<0.05) and C20:5omega3 (P<0.05) than M. iliofibularis. Citrus pulp diet increased (P<0.05) meat ultimate pH and reduced cooking losses (P<0.05) as compared to the control diet. Meat from animals given citrus pulp had lower crude fat (P<0.05) and ash percentages (P<0.05) in comparison to that from the control group. The proportions of intramuscular saturated and monounsaturated fatty acids were lower (P<0.05) in the citrus pulp group as compared to the control one. Meat from the citrus pulp treatment group had a higher (P<0.05) percentage of polyunsaturated fatty acids than meat from the control treatment. In particular, meat from ostriches given citrus pulp diet exhibited higher C18:2omega6 (P<0.05) and C20:4omega6 (P<0.05) contents that accounted for a higher omega6/omega3 ratio (P<0.05) as compared to the control group. Overall, the use of a citrus pulp included diet in ostrich feeding did not adversely affect meat quality and, therefore, citrus pulp seems to be a possible ingredient to reduce feeding costs. PMID- 22062237 TI - Water, sodium chloride and acidified sodium chlorite effects on Escherichia coli O157:H7 and Staphylococcus aureus on beef briskets. AB - Effectiveness of spray application of potable water wash (WW), 25% (w/v) sodium chloride (NaCl), and 0.1% (v/v) acidified sodium chlorite (ASC) was evaluated against Escherichia coli O157:H7 and Staphylococcus aureus inoculated onto beef briskets. The purpose was to identify antimicrobial treatments which may be applied to beef carcasses and more specifically in kosher meat facilities. Treatments were applied for 10-60 s at pressure of 419 kPa. Water wash, NaCl, and ASC significantly reduced E. coli O157:H7 as compared with the control, although, only ASC resulted in improved removal with increased exposure time. Water wash did not significantly reduce S. aureus counts throughout exposure and NaCl was only effective after 60 s of exposure, while ASC reduced counts throughout exposure. E. coli O157:H7 was twice as sensitive to WW and NaCl as S. aureus in terms of percent reduction in cell count. PMID- 22062238 TI - Growth and carcass characteristics of pasture fed LHRH immunocastrated, castrated and intact Bos indicus bulls. AB - The effectiveness of a luteinizing hormone-releasing hormone (LHRH) fusion protein vaccine or surgical castration, at two years of age, on growth and carcass characteristics of Bos indicus bulls was evaluated. Seventy Nelore-cross bulls were divided into three groups: (1) immunized, (2) castrated and (3) intact control. At slaughter (three years of age), intact bulls had higher body weights, ADG, carcass weights, and muscle percentage compared to immunized and surgically castrated animals. Both castrated and immunized animals had greater marbling and percent carcass fat than the intact bulls. Average tenderness scores were inferior for intact bulls compared to immunized and castrated animals, but these differences were not significant (P>0.05). Juiciness, flavor, thawing, nor cooking losses differed significantly among the three groups. Immunocastration was effective in producing carcass traits similar to that of surgical castration. Therefore, immunization with LHRH fusion proteins appears to have practical utility in the management and castration of grazing bulls. PMID- 22062239 TI - Effects of fat level (5%, 10%, 20%) and corn flour (0%, 2%, 4%) on some properties of Turkish type meatballs (koefte). AB - In this study the effects of fat level (5%, 10% and 20%) and corn flour (CF 0%, 2% and 4%) on chemical composition, cooking characteristics and sensory properties of Turkish type meatballs were evaluated. Cooking characteristics were evaluated by measuring cooking yield, fat retention, moisture retention, reduction in diameter and thickness and shrinkage. At each fat level, incorporation of CF significantly increased protein content but had no significant effect on fat content of cooked meatballs. Decreasing the fat content from 20% to 5% significantly increased cooking yield and fat retention. Meatballs formulated with 20% fat had the highest reduction in diameter. CF had no effect on reduction in diameter. CF reduced shrinkage in meatballs formulated with 5% or 10% fat and increased moisture retention in treatments formulated with 5% or 10% fat. Sensory evaluation indicated that decreasing fat level resulted in lower texture and overall palatability scores. CF had no detrimental effect on sensory properties except appearance. PMID- 22062240 TI - Carcass and beef color characteristics of three biological types of cattle grazing cool-season forages supplemented with soyhulls. AB - Soyhull supplementation to divergent biological types of cattle on forage-based systems was studied to determine the impact on carcass and color characteristics. Weaned calves (n=107) biologically classified as large-, medium-, or small-framed and intermediate rate of maturing were allocated to three cool-season grazing systems consisting of either orchardgrass pasture or fescue pasture, each with soyhull supplementation, or fescue pasture with no supplementation as a control. Supplementing cattle with soyhulls allowed for heavier (P<0.05) live and carcass weights, larger (P<0.05) longissimus muscle area, increased (P<0.05) backfat, kidney, pelvic and heart fat (KPH), and yield grades, and improved (P<0.05) marbling scores and quality grades. Utilizing cattle biologically classified as large- or medium-framed allowed for heavier (P<0.05) carcass weights without reducing (P<0.05) marbling scores or quality grades when compared to small-framed cattle. Instrumental color analysis of lean and adipose tissue revealed improved (P<0.05) lightness (L (*)) in lean color for supplemented carcasses as compared to the control. There were no differences (P<0.05) between dietary treatments for L (*), a (*) or b (*) values of adipose tissue. These results indicate that supplementing forage-grazing cattle with soyhulls can improve carcass merit, and utilizing large- or medium-framed cattle can allow for increased carcass weights without decreasing carcass quality. PMID- 22062241 TI - Injection of salt, tripolyphosphate and bicarbonate marinade solutions to improve the yield and tenderness of cooked pork loin. AB - Several marinade solutions were tested for their effects on pork tenderness. Paired loins were removed from eight Large White crossbred pigs. Each pair was cut to give eight pieces and injected to a target of 110% of original weight with one of the following eight solutions (g/100 g water): uninjected (A, control), 5% salt (B), 5% sodium tripolyphosphate (C), 3% sodium bicarbonate (D), 5% salt and 5% sodium tripolyphosphate 5% (E), 5% salt and 3% sodium bicarbonate (F), 5% sodium tripolyphosphate and 3% sodium bicarbonate (G), 5% salt, 5% sodium tripolyphosphate and 3% sodium bicarbonate (H). Samples were left overnight to equilibrate, cooked and assessed for tenderness using a Volodkevich shear force method. Mean pHs for meat injected with phosphate and/or bicarbonate (C-H) ranged from 5.75 to 5.97, compared to 5.45 for the control. All injected loins, had a significantly higher yield than the control (p<0.05), except salt alone which, though higher, did not differ significantly (p>0.05) from the control. Treatment H increased the yield from 70% (control) to 85%. All marinades significantly reduced the shear force (p<0.05), some treatments (D and F) by up to a half compared to the control (5150 g). Individual animal results suggest that marination could be used to good effect even in the toughest samples, whilst improving tender samples still further. Samples treated with bicarbonate had an usual porous structure, probably due to carbon dioxide produced during cooking which may have contributed to the reduced toughness. PMID- 22062242 TI - Establishment of a model experiment system to elucidate the mechanism by which Zn protoporphyrin IX is formed in nitrite-free dry-cured ham. AB - The aim of this study was to establish a model experiment system to elucidate the mechanism by which Zn-protoporphyrin IX (ZPP) is formed in Parma ham. The established model consisted of myoglobin, meat and antibiotics, and incubation under anaerobic conditions resulted in a greater yield of ZPP. Formation of ZPP was observed even in the presence of various antiseptics. The amount of ZPP formed increased as the period of incubation increased. ZPP formation was inhibited by heating meat homogenate depending on the heating temperature. Our results show that anaerobic conditions are suitable for the formation of ZPP in meat products without nitrate or nitrite and that endogenous enzymes as well as microorganisms may be involved in ZPP formation. PMID- 22062243 TI - Effect of Debaryomyces spp. on the proteolysis of dry-fermented sausages. AB - The effect of the addition of Debaryomyces spp. on the microbial, chemical properties and degradation of meat proteins in dry fermented sausages was investigated. The manufacture of dry fermented sausages with Debaryomyces spp. produced a slow decline in pH during early drying stage. However, the final product had lower ammonia, and higher acetic and d-lactic acids without producing any effect on the final pH. Sarcoplasmic proteins were not affected by Debaryomyces spp. but the degradation of myofibrillar proteins was accelerated at the beginning of the drying stage even though the final sausage, inoculated with Debaryomyces spp., had lower myofibrillar proteolysis. The content of free amino acids was similar at the beginning of the drying stage for all the studied batches. However, the high differences in the content of free amino acids at the end of the process could be attributed to the Debaryomyces spp. activity. The addition of a higher amount of Debaryomyces spp. did not contribute to a major proteolysis degree. PMID- 22062244 TI - Effectiveness of transdermal, needle-free injections for reducing pork carcass defects. AB - A needle-free, transdermal injection device was evaluated for effectiveness of vaccine delivery and for injection site lesions in swine. A total of 130 pigs were vaccinated for pseudorabies virus (PRV) and Mycoplasma hyopneumoniae (M. hyopneumoniae). Pigs were divided into three groups; one group served as unvaccinated controls, the second group was vaccinated with conventional hypodermic needles and the third group was vaccinated with a needle-free, airpowered transdermal injection device. Blood samples collected for up to 36 days post-injection showed that both injection methods produced similar serological responses that were significantly greater than for unvaccinated controls. Injection sites, collected at slaughter from each carcass, showed minimal development of lesions and no carcass defects. The results show the needle-free, transdermal injection system to be effective and safe. Elimination of needles will prevent residual needle fragments in carcasses and associated carcass defects that develop from needle-induced injection-site lesions. PMID- 22062245 TI - Microbiological conditions of air knives before and after maintenance at a beef packing plant. AB - Microbiological samples were obtained from air knives i.e., hand-held tools powered by compressed air, which were used during beef carcass skinning, and from equipment used for their maintenance. Bacteria from samples were enumerated by hydrophobic grid membrane filtration procedures. Knives presented for maintenance yielded aerobes at log mean numbers about 6 log cfu/knife, and coliforms, Escherichia coli and aeromonads at log total numbers about 4 log cfu/25 knives. After degreasing and at all subsequent stages of maintenance, the numbers of each group of bacteria were about 2 log units less. The numbers of bacteria recovered from the blade polishing machine were similar to the numbers recovered from knives presented for maintenance, but fewer bacteria were recovered from the blade sharpening machine. The findings suggest that it is possible for meat to be contaminated with hazardous bacteria derived from populations that persist on powered tools used for carcass dressing and on maintenance equipment. PMID- 22062246 TI - Single-trial event-related potentials and autonomic measures of the orienting reflex. AB - We aimed to clarify the event-related potentials (ERPs) associated with elicitation and habituation of the basic Orienting Reflex (OR). Participants were presented with 16 innocuous tones, alternating in intensity, at long variable inter-stimulus intervals, with no task. This allowed us to examine stimulus novelty and intensity effects in the absence of stimulus-related task demands. Single-trial ERPs were extracted to obtain estimates of the early N1 and the late positive complex (LPC) to each stimulus. Electrodermal responses showed substantial main effects of trials and intensity, supporting their functionality as an OR index. Cardiac deceleration showed no systematic change with intensity or trials, suggesting that it marks the transient onset of each stimulus, early in the stimulus-processing sequence. Respiratory pause showed a substantial main effect of trials but no intensity effect, suggesting that it reflects an intermediate processing stage. A main effect of intensity, but no simple trial effect, was apparent in the N1, suggesting that it reflects a different intermediate processing stage. The subsequent LPC showed only a topographic interaction with trials and intensity, failing to support any substantive role in OR processing. These different stimulus-response profiles are discussed in the context of a sequential processing model of the OR. PMID- 22062247 TI - beta-1,3-Glucan recognition protein (betaGRP) is essential for resistance against fungal pathogen and opportunistic pathogenic gut bacteria in Locusta migratoria manilensis. AB - Pattern recognition proteins, which form part of the innate immune system, initiate host defense reactions in response to pathogen surface molecules. The pattern recognition protein beta-1,3-glucan recognition protein (betaGRP) binds to beta-1,3-glucan on fungal surfaces to mediate melanization via the prophenoloxidase (PPO)-activating cascade. In this study, cDNA encoding a 53-kDa betaGRP (LmbetaGRP) was cloned from Locusta migratoria manilensis. LmbetaGRP mRNA shown to be constitutively expressed specifically in hemocytes and was highly upregulated following fungal infection. LmbetaGRP-silenced (LmbetaGRP-RNAi) mutant locusts exhibited significantly reduced survival rate following fungal infection (Metarhizium acridum) compared with the wild-type. Furthermore, LmbetaGRP-RNAi mutants exhibited abnormally loose stools indicative of a gut defect. 16S rRNA gene analysis detected the opportunistic pathogenic bacterium, Vibrio vulnificus in LmbetaGRP mutant but not wild-type locusts, suggesting changes in the composition of gut bacterial communities. These results indicate that LmbetaGRP is essential to gut immunity in L. migratoria manilensis. PMID- 22062248 TI - Response to Letter to the Editor: Advantages of electrical stimulation. PMID- 22062249 TI - Effect of rearing system on muscle lipids of gilts and castrated male pigs. AB - The objective of this study was to investigate the polar and neutral lipid fatty acid composition of pig muscle as influenced by rearing conditions and sex. A total of 120 Hampshire crossbreeds were divided in two groups, one reared free range in a strip grazing fashion and one reared indoors in a large pen (120 m(2)). Free-range rearing produced a more unsaturated fatty acid composition (M. biceps femoris) in the neutral lipids, although the effect was small. In the polar lipids the effect of rearing condition was sex dependent. In the muscle of free-range gilts, there was a higher level of C18:2 n-6, compared with indoor gilts, indoor castrates, and free-range castrates. Moreover, muscle of gilts irrespective of rearing condition, had a higher level of the C?20 polyunsaturated fatty acids in the polar lipids (16.75 and 14.60, respectively). Thus, we suggest that the difference between castrates and gilts with respect to fatty acid composition in the polar lipids, might be affected by rearing condition. PMID- 22062250 TI - Effect of low voltage electrical stimulation and temperature conditioning on postmortem changes in glycolysis and calpains activities of Korean native cattle (Hanwoo). AB - The combined effects of low voltage electrical stimulation (LVES) and temperature conditioning during early postmortem (PM) ageing on glycolytic rates and calpains activities of Korean native cattle (Hanwoo) were determined. M. longissimus was taken after splitting course, divided into three pieces and temperature conditioned at 2, 16, and 30 degrees C for 3 h PM. The PM glycolytic rates, calpains and calpastatin activities were measured at 1, 3, 9, and 24 h PM. Although both LVES and the 30 degrees C treatment accelerated glycolytic rates and resulted in improved enzyme activities, LVES was more effective for the improvement of enzyme activities than the 30 degrees C treatment. Among tested Rigor-values (R-value; R(248), R(250), and R(258)), R(258) showed the highest correlation with pH (r=0.814, P<0.01), glycogen content (r=0.784, P<0.01) and MU calpain (r=0.838, P<0.01) and selected as a suitable parameter to predict glycolytic rate. The high correlation coefficients between MU-calpain activity and metabolic rate parameters suggest that the change in the enzyme activity is closely related to glycolytic rates. The LVES in combination with the 30 degrees C treatment until 3 h PM was the best treatment to accelerate the glycolytic rate and to improve the calpains activities in Hanwoo tissue. PMID- 22062251 TI - Evaluation of electric belt grill, forced-air convection oven, and electric broiler cookery methods for beef tenderness research. AB - Five muscles from USDA Select beef carcasses were cooked on an electric belt grill at three temperatures (93, 117, and 163 degrees C), in a forced-air convection oven, and on an electric broiler to determine effects of cooking treatment and muscle on Warner-Bratzler shear force values, cooking traits (cooking loss, cooking time, and endpoint temperature), and repeatability of duplicate measurements. All cooking treatments allowed shear force differences to be detected (P<0.05) among the five muscles, although the differences were inconsistent. Neither longissimus lumborum nor semitendinosus shear values differed among the five cooking treatments; however, shear values for biceps femoris, deep pectoralis, and gluteus medius differed (P<0.05) among cooking treatments. Belt grill cooking resulted in the highest shear force repeatability (R=0.70 to 0.89) for the longissimus lumborum. All cooking methods provided acceptable repeatability (R?0.60) of shear values for the biceps femoris and semitendinosus. The electric broiler was the only cooking treatment that resulted in acceptable repeatability of shear force measurements for all five muscles. It is not recommended to use the gluteus medius to test treatment effects on shear force values. Belt grill or electric broiler cooking are recommended for shear force evaluations. PMID- 22062252 TI - The preference of the consumer for pork from homozygous or heterozygous halothane negative animals. AB - To evaluate the taste preference of the consumer for meat from homozygous (NN) halothane negative pigs or heterozygous (Nn) halothane negative pigs, a consumer test was conducted at the "Agriflora" exhibition, concerning Flemish agriculture and horticulture, held from 8 to 10 January 1999 in Ghent, Belgium. The carcass quality of both tested genotypes was similar, while acidity, colour and drip loss were inferior and cooking loss and Warner-Bratzler shear force superior for the Nn pigs compared with the NN pigs. One hundred and seventy-one visitors completed the test correctly. No significant difference was found between NN- and Nn-meat for the tastiness scores. These results do suggest that elimination of the halothane gene from the pig population does not guarantee a better eating quality of the meat. PMID- 22062253 TI - Presensitization of microorganisms by acid treatments to low dose gamma irradiation with special reference to Bacillus cereus. AB - Effect of acid presensitization to low dose gamma irradiation on Bacillus cereus in sheep/goat meat stored at refrigeration temperature was assessed. Food grade organic acids (viz. propionic, lactic and acetic acids) were used as presensitizers followed by treatment with 1, 2 and 3 kGy irradiation doses (Co(60)). Two percent acetic acid plus 3 kGy irradiation elicited most effective to lower the total viable count and B. cereus count. Combination of treatments availed to reduce the dose required for elimination of radioresistant B. cereus and also masked the irradiation odour developed due to radiolysis. The study also revealed substantial increase in shelf life of mutton after combination treatment than single treatment without any adverse effect on acceptability of meat. PMID- 22062254 TI - The use of multivariate analysis for evaluating relationships among fat depots in heavy pigs of different genotypes. AB - The aim of the present work was to study distribution and reciprocal relationships of fat depots in heavy pigs of several genetic types. On 161 barrows and gilts belonging to four genetic types (Large White and relative crosses with Italian Landrace, Belgian Landrace and Duroc), slaughtered from 125 to 180 kg l.w., thickness, colour (C.I.E, L*, a*, b*) and weight of backfat and of kidney fat were determined. Subcutaneous and intermuscular fat of ham were weighed. On biceps femoris, semimembranosus and semitendinosus muscles ether extract content was determined. Allometric analysis showed that body growth did not particularly increase the intramuscular fat content of the ham. Principal component analysis indicated that PC1 (0.43% of variation) represented the overall fatness, associated all the depots in a similar manner, and was linked to body weight and sex. PC2 (0.22% of variation), linked to genotypes and body weight, expressed the opposition between intramuscular fat deposition and subcutaneous and internal fat accumulation. Using measurements easily recorded on the side (backfat thickness and colour, percent kidney fat), only the estimate of subcutaneous fat, among ham depots, showed good accuracy (R(2)=0.65). PMID- 22062255 TI - Free range rearing of pigs with access to pasture grazing - effect on fatty acid composition and lipid oxidation products. AB - The influence of free-range rearing, RN genotype and sex on different pig meat quality traits, including intramuscular fatty acid composition and levels of lipid oxidation products, were studied. A total of 60 Hampshire crossbred pigs were reared outdoors for two months with access to green feed, while 60 others were kept indoors, in a 120-m(2)-large pen, throughout the rearing period. From these 120 animals a subsample of 44 animals was chosen for meat quality analysis. Of the three factors studied, the RN genotype had the largest influence on basic technological meat quality traits, whereas the rearing conditions and sex had limited effects. However, outdoor rearing resulted in higher levels of polyunsaturated fatty acids in the intramuscular fat (P=0.026) and in an increased level of vitamin E (P=0.030) compared with the pigs that had been reared indoors. The sex and RN genotype of the animals also had an effect on the fatty acid profile: females had higher levels of unsaturated fatty acids (P=0.003) as well as lower levels of saturated fatty acids (P=0.011) than castrated males. Carriers of the RN(-) allele expressed a higher sum of omega-3 fatty acids (P=0.047) and C22:5 (P=0.012) than did the non-carriers. In a storage study where meat from free-range and indoor reared pigs was stored for 3 months at-20 degrees C, it was shown that the lipid oxidation product malondialdehyde was formed at increased levels in animals that had a higher lean meat percentage than others, i.e. females that were carriers of the RN(-) gene and that were reared outdoors. PMID- 22062256 TI - Effect of suckling on growth and quantitative and qualitative carcass traits of once-calved heifers. AB - Heifers (n=72) from four breed-types were used to evaluate the effect of breed type and parity/weaning age on growth performance and carcass characteristics of the heifers. Breed-types studied were Japanese Black (B), B*Holstein (BHo), B*BHo (BBHo), and Japanese Shorthorn (S)*B (SB); whereas parity/weaning age treatments included maiden heifers and two once-calved heifer groups in which calves weaned at either 7 or 105 days. Growth performance of the once-calved heifers was inversely proportional to the milking ability of the heifers. Differences of carcass quality were significant (P<0.05) among breed-types, but not significant (P>0.05) among parity/weaning age groups by finishing for 180 days after weaning the calves. PMID- 22062257 TI - Tenderization of chicken and turkey breasts with electrically produced hydrodynamic shockwaves. AB - Eighty early deboned (45 min, post mortem) postrigor chicken breasts were exposed (24 h post mortem) to two levels (number of pulse firing networks, PFN; 45% energy) of electrically produced hydrodynamic shockwaves (HSW). In addition, 21 turkey breasts (72 h post mortem) were HSW treated (two PFN, 72% energy). Samples were water cooked in bags (78 degrees C internal). Two PFN's were required to decrease (P<0.05) chicken Warner-Bratzler shear (WBS) force by 22% from the control (4.67 kg). WBS force of the HSW treated turkey breast decreased (P<0.05) by 12% from the control (3.20 kg). Cooking loss was higher (P<0.05) in the turkey breast portions but not in the chicken breasts. The electrically produced shockwave process has the potential to provide chicken processors with the ability to early debone and produce tender breasts and to provide turkey processors with tenderness-enhanced fillets. PMID- 22062258 TI - Hydrodynamic shockwave tenderization effects using a cylinder processor on early deboned broiler breasts. AB - In separate experiments, chicken broiler breasts were deboned (45 min postmortem, 52 min, respectively) and either exposed to high pressure hydrodynamic shockwaves (HSW) 25 min after deboning (77 min postmortem) or after 24 h of storage (4 degrees C) respectively, and compared to companion control breasts. HSW were produced in a cylindrical HSW processor with 40-g explosive. Warner-Bratzler shear (WBS) values of the HSW breasts treated at 77 min postmortem were not different than the controls. HSW treatment decreased (P<0.05) the WBS values of the stored and cooked breasts by 42.0% as compared to non-treated controls. Cooking losses were not affected by HSW. In general, raw and cooked color characteristics (CIE L*a*b*) were not affected by the HSW. HSW treatment at 25 min after deboning (77 min postmortem) may require a higher pressure front or delayed treatment after postmortem aging to improve tenderness. PMID- 22062259 TI - Fatty acid composition of M. longissimus lumborum, ultimate muscle pH values and carcass parameters in reindeer (Rangifer tarandus tarandus L) grazed on natural pasture or fed a commercial feed mixture. AB - The effects of feeding regimen on the fatty acid composition of M. longissimus, ultimate pH values in three muscles (Mm. longissimus, triceps brachii and biceps femoris) and carcass quality were studied in15 reindeer bulls. Nine animals came from natural pasture and six had been fed a pelleted commercial feed mixture for two months prior to slaughter. The pellet fed reindeer had significantly better carcass grading scores (EUROP conformation), higher trim fat content, more intramuscular fat and lower ultimate pH values in all three muscles than the group from pasture. The polar and neutral lipid fatty acid composition of the meat was analysed separately. Meat from pasture fed reindeer showed a high content of the fatty acid 18:3 n-3 in the polar lipid fraction. In the same lipid fraction, the fatty acid 18:2 n-6 was dominant in meat from the pellet fed animals. Similar differences in the neutral lipid fraction were found when comparing fatty acid composition between treatment groups, however the abundance of these fatty acids was much less. The present results confirm previous findings that reindeer fed typical pelleted commercial feed mixtures generally have an improved nutritional status. PMID- 22062260 TI - Determination of fatty acid composition of pork fat by Fourier transform infrared spectroscopy. AB - The fatty acid composition of pork fat determines its processing quality. FTIR spectroscopic methods were evaluated on pork back and breast fat, directly on fat slices and on the fat extracts. Near infrared transmission and middle infrared using an ATR method were developed to determine the fatty acid content in the fat extracts. The results obtained with 80 back and 80 breast samples showed the validity of infrared spectroscopy to estimate SFA (saturated fatty acids), MUFA (monounsaturated fatty acids), PUFA (polyunsaturated fatty acids), C16:0, C18:0, C18:1 and C18:2 contents in fat extracts. Correlation coefficients (R(2)) were around 0.91 and 0.98 for MIR (ATR) and around 0.85 and 0.96 for NIR (transmission). Direct measurements on fat slices by NIR predicted SFA, PUFA, C18:1 and C18:2, although the coefficient correlations were less good; 0.69-0.79. This method though, is easier and faster than other techniques and is accurate enough to discriminate fat samples separated by standard visual and texture classification. Measurements could be made in 1 min. PMID- 22062261 TI - Evaluation of the electrical impedance spectroscopy (EIS) equipment for ham meat quality selection. AB - The objective of this study was to evaluate the electrical impedance spectroscopy (EIS) prototype, to select the hams on the basis of meat quality characteristics in commercial conditions. Measurements of meat quality were made on 95 commercial hams (11.10+/-0.76 kg) to evaluate quality characteristics [ham weight, conformation (H), fat thickness in the rump (FTR), visual fatness (VF), pH(45), electrical conductivity (QM(45)) and ultimate pH (pH(24,) pH(36)) in the semimembranosus muscle]. The electrical parameters, Ro, Rinf, Ratio (Rinf/Ro), Fc and alpha, were obtained with the EIS equipment and was applied in five different regions of the ham (M, SM, M1, M2 and AD) at 36 h post-mortem. Principal component (PC) analysis has been used to describe the relationships between meat quality and electrical parameters in the ham meat. Two regions were selected, SM and M, showing the best correlations with pH(45) and fat characteristics in relation to electrical parameters Rinf and Ratio, respectively. Multiple regression analysis of the data confirmed that electrical variables, Ratio, alpha and Fc contributed to predict pH(45) (R(2)=0.50). In order to better predict visual fatness (VF), conformation and ham weight were included in the multiple regression. A R(2) of 0.59 was obtained with H, Rinf, ham weight and alpha. In conclusion, the results of this study have demonstrated that ratio in the SM region may classify with 88.46% accuracy the technologically normal meat (pH(45) > 6.10) from the PSE meat. In relation to visual fatness of the ham 84.21% of the samples with a Rinf in the M region > 56 had a score of > 2.5. PMID- 22062262 TI - Effects of the stunning procedure and the halothane genotype on meat quality and incidence of haemorrhages in pigs. AB - A total of 313 pigs (127 halothane-free, NN, and 186 heterozygous halothane, Nn) were slaughtered in four batches at two commercial abattoirs with two different stunning systems, an automatically head-only followed by head-to-chest electrical stunner and a compact carbon dioxide (CO(2)) stunning unit. Meat quality on the loin muscle was assessed by measuring electrical conductivity (PQM) and colour (Minolta CR 200) at 7 h post mortem, and ultimate pH. Loins showing PQM >6.0 MUs were classified as clearly pale, soft and exudative (PSE) meat. The incidence of petechiae, ecchymosis and haematomas in the shoulders, loins and hams was also evaluated. In the abattoir equipped with the electrical stunning system, a higher incidence of potentially PSE meat was found compared with the abattoir equipped with CO(2) stunning (35.6 vs. 4.5%). Likewise, electrical stunning increased significatively the incidence of petechiae in the loins, shoulders and hams, and ecchymosis in the loins and hams. Also, the incidence of PSE meat was higher in the Nn pigs compared with NN pigs (24.7 vs. 7.9%). It is suggested that for improving meat quality and reducing incidence of haemorrhages electrical stunning should be avoided. Further improvements in meat quality can be achieved by eliminating the halothane gene specially in CO(2)-stunned pigs. PMID- 22062263 TI - Fatty acid composition, cooking loss and texture of beef patties from meat of bulls fed different fats. AB - The effect of fatty acid composition on the properties of patties standardised to contain 15% fat was studied. Patties were made of beef from 36 Brown Swiss bulls fed on six different diets with five of them containing additional fats to achieve a high variability in body lipid composition. When the feed contained fullfat oilseeds (rapeseed, sunflower seed, linseed), the proportions of some nutritionally favourable fatty acids were increased in the patties. Patties made from the meat of bulls fed linseed and coconut oil could be distinguished in a sensory triangle test from most other groups. Cooking loss and instrumental texture properties showed no relation to fatty acid composition of patties. Cooking only slightly decreased the proportion of saturated fatty acids in favour of polyunsaturated fatty acids. In conclusion, widely differing dietary fats can be fed to bulls without risking major effects on texture of beef patties. PMID- 22062264 TI - Superficial contamination of bovine carcasses by Escherichia coli O157:H7 in a slaughterhouse in Normandy (France). AB - In 1997, analyses were carried out on 255 bovine carcasses to determine the extent of superficial contamination by E. coli O157. A 50-cm(2) meat sample taken from all carcasses was collected and tested using immunomagnetic separation method to detect E. coli O157. One strain of E. coli O157 bacterium was isolated and sent to the reference national center (Institut Pasteur, Paris). The strain was confirmed as E. coli O157:H7 and found to contain two out of the three pathogenicity genes (eae and EHEC-hlyA) necessary for enteropathogenicity. Shiga toxin genes were not detected. Superficial contamination of E. coli O157:H7 was established, but at low level (0.4%). PMID- 22062265 TI - Relationship between beef consumer tenderness perception and Warner-Bratzler shear force. AB - The aim of this study was to determine consumer ability to discern different levels of beef tenderness established by Warner-Bratzler shear (WBs). A panel of 220 people evaluated 60 samples of longissimus thoracis using a 5-point intensity scale (1: very tough; 5: very tender). Samples differed for commercial category, breed of animals and ageing length of meat. Shear force was measured by Instron equipped with a Warner-Bratzler device on 1.27cm diameter cores. Correlation coefficient of WBs measurements with tenderness sensory ratings was -0.72. WBs value corresponding to class 3 of the sensory tenderness was 47.77N. From this value, the range of WBs (22.96-72.59N) was split into five categories to which connect the five classes of sensory tenderness. The results suggest consumers' difficulty in discriminating category 1 (WBs>62.59N) from category 2 (WBs: 52.78 62.59N) and a greater inclination to distinguish category 5 (WBs<32.96N). As WBs category boundaries were probably too restrictive for the panel's selective ability, WBs scale was reduced to 3 categories by joining the two extreme categories (i.e. category 2 with 1 and category 4 with 5). In this case, 55.6% of consumers significantly discriminated tough from intermediate and tender meat and 62.3% distinguished tender from intermediate and tough meat (P<0.01). Hence, WBs values >52.68N and <42.87N allow classification of tough and tender beef in a sufficiently reliable way. PMID- 22062266 TI - Fatty acid composition of M. Longissimus dorsi from Holstein-Friesian steers of New Zealand and European/American descent and from Belgian Blue*Holstein-Friesian steers, slaughtered at two weights/ages. AB - Our objective was to determine the effect of breed (B) and slaughter age/weight on the fatty acid composition, particularly the conjugated linoleic acid (CLA) concentration of beef. Two strains of a dairy breed [Holstein-Friesian (HF) (n=16 steers/strain)] and a late-maturing breed [Belgian Blue*Holstein-Friesian (BB) (n=16 steers)] were used. The HF strains were either of New Zealand (NZ) or European-American (EU) descent (selected in a grazed grass or a high concentrate nutritional environment, respectively). Animals were grown from calves to either a light (L; 560kg) or heavy (H; 630kg) target slaughter weight. Samples of M. longissimus dorsi were collected post-slaughter, lipids were separated into neutral (NL) and polar (PL) fractions, and fatty acid composition determined by gas-chromatography. The total fatty acid concentration and the concentrations of cis9, trans11 CLA, total CLA, MUFA and SFA in total intramuscular lipids were lower and the P:S ratio higher for BB than NZ or EU which did not differ. These differences largely reflected the changes in NL. The C18 desaturase index was higher for NZ than EU but EU did not differ from BB. Increasing slaughter weight/age increased the total fatty acid concentration and the concentrations cis9, trans11 CLA (P=0.06), total CLA (P=0.06), trans11 C18:1, MUFA and SFA and the C18 desaturase index and decreased the P:S ratio. The n-6:n-3 PUFA ratio was similar at the lighter slaughter weight/age for the three breeds/strains but increased for NZ and EU with increasing slaughter weight/age but was not affected in BB. It is concluded that the CLA concentration largely reflected muscle fatness but that increasing slaughter weight/age differentially affected the n 6:n-3 PUFA ratio of beef from early and late-maturing cattle. PMID- 22062267 TI - A second look at the influence of birth weight on carcass and meat quality in pigs. AB - To re-examine the relationship of birth weight with carcass and meat quality of pigs at market weight, offspring (n=378) of 63 sows were assigned to three birth weight groups; 25% low weight (LW), 50% middle weight (MW), and 25% heavy weight (HW), with runts (<800g) being excluded. LW pigs exhibited the lowest postnatal growth performance, the lowest lean mass and the greatest degree of fatness in terms of perirenal fat compared with MW and HW pigs. Only in females, but not in male castrates, the lean percentage was highest in HW pigs. Characteristics of longissimus muscle technological quality declined either in LW (pH, drip loss) or HW (conductivity, lightness) compared with MW pigs. In contrast, intramuscular fat percentage (IMF) was highest in LW pigs. The results suggest that the most desirable carcass composition is obtained with HW pigs, whereas optimum technological pork quality, except for IMF, is achieved with MW pigs. PMID- 22062268 TI - A comparison of organic and conventionally-produced lamb purchased from three major UK supermarkets: Price, eating quality and fatty acid composition. AB - Organic and conventional lamb loin chops, labelled as British lamb, were bought from three major UK supermarket chains (designated A, B and C) in the Bristol area on 10 occasions over a six week period. Samples (n=360) were from unknown production systems but representative of what is available to UK consumers. The nutritional quality of muscle was assessed in terms of its fatty acid composition and eating quality was assessed by a trained sensory panel. Lamb prices varied between L9 and L12.50 per kg, with a relatively modest price differential between organic and conventional lamb chops of L1.10, L1.88 and L1.16 L/kg for supermarkets A, B and C, respectively. On average, organic chops were 20g heavier than conventional chops. Chops were relatively lean, having just 14% of subcutaneous fat, approximately half that of a similar survey 10 years ago. Organic lamb had a better eating quality than conventional lamb in terms of juiciness (p<0.05), flavour (p<0.05) and overall liking (p<0.05) thus providing some evidence for the perception among consumers that organic products 'taste better'. Differences in juiciness were attributed to the higher intramuscular fat content of organic meat whilst differences in flavour were attributed to differences in fatty acid composition, in particular, the higher level of linolenic acid (18:3) and total n-3 PUFA in organic chops. Conventional chops had a higher percentage of linoleic acid (18:2). Chops from both productions systems had a favourable n-6:n-3 ratio. The most important difference between the three supermarkets was that lamb flavour was significantly lower in chops from supermarket A, probably due to differences in their 'display until' dates. Chops from supermarket A were also the cheapest. PMID- 22062269 TI - Carcass composition and yield of Alaskan reindeer (Rangifer tarandus tarandus) steers and effects of electrical stimulation applied during field slaughter on meat quality. AB - Twenty six adult reindeer steers (>3 years old) were used in a study to evaluate the effect of electrical stimulation (ES) on the quality of hot-boned, rapidly frozen shoulder meat and of the striploin (M. longissimus, LD) from carcasses held at +3 degrees C for 48h. Carcass yield and composition was determined from the left carcass half from which the shoulder meat was not removed. The shoulder meat was processed frozen into cubed, sliced or ground products. Proximate composition of the LD, meat color and water-holding capacity were very similar for the ES (n=15) and non-electrical stimulation (NES; n=11) groups. Ultimate pH and shear force values were significantly lower in the ES meat (LD), however a trained sensory panel could not detect differences between the two groups in any of the measured sensory attributes. Consumer preference tests demonstrated that ES increased tenderness in the cubed and sliced products made from field slaughtered reindeer shoulder meat. ES in combination with hot boning and processing of boneless frozen meat can be used in field slaughter systems for reindeer to improve meat quality and to increase the potential value of the carcass. PMID- 22062270 TI - Use of gamma-irradiation to reduce Clostridium perfringens on ready-to-eat bovine tripe. AB - The aim of this study was to determine the effect of gamma irradiation at a target dose of 9kGy and storage at 5 and 15 degrees C on the safety of ready-to eat (RTE) tripe with respect to Clostridium perfringens count (CC) and aerobic plate count (APC), and to determine the effect of boiling (1h) and irradiation (9kGy) on Cl. perfringens ATCC 13124 spore structure. Irradiation significantly reduced APC stored at 5 and 15 degrees C for 7 days. However, 0kGy control samples increased in their APC to >7log(10) cfu/g throughout 7 days of storage. Irradiation eliminated the inoculated Cl. perfringens ATCC 13124 spores on RTE tripe throughout storage at 5 and 15 degrees C. Transmission electron microscopy of Cl. perfringens ATCC 13124 spores showed that boiling caused a reduction in spore material, irradiation caused elongation of the Cl. perfringens ATCC 13124 spores, and boiling in combination with gamma irradiation caused loss of spore material. Therefore, irradiation at 9kGy, together with storage at 5 degrees C, can assure the microbiological safety of RTE bovine tripe, with respect to Cl. perfringens spores for at least 7 days at 5 and 15 degrees C. PMID- 22062271 TI - Effect of glycogen concentration and form on the response to electrical stimulation and rate of post-mortem glycolysis in ovine muscle. AB - The associations between the muscle glycogen concentration and form and the rate of post-mortem glycolysis in ovine muscle were investigated. Twenty-two merino wethers (18-24 months) were allocated to either roughage or concentrate pelleted diets for 34 days prior to slaughter. An exercise depletion/repletion model was applied four days prior to slaughter to generate differences in muscle glycogen levels at slaughter. Muscle biopsies were taken from the m. semimembranosus (SM) and m. semitendinosus (ST) prior to and immediately after exercise for muscle glycogen determination. At slaughter, one side was electrically stimulated and both sides were conventionally chilled for 24h. The pH response to electrical stimulation (DeltapH) and the rate of pH decline adjusted to a constant temperature of 38 degrees C over the initial 6h post-mortem period was determined in three muscles (m. longissimus thoracis et lumborum LTL, SM and ST). In addition, the concentrations of glycogen, proglycogen (PG), macroglycogen (MG) and lactate in the three muscles immediately after slaughter were determined. The glycogen loss due to exercise was influenced by diet (P<0.01; concentrate 63% and roughage 73%) but did not differ between muscles. The rates of repletion significantly varied between muscles (SM>ST) and diet (concentrate>roughage). The available glycogen (glycogen(A)) and MG concentrations at slaughter varied significantly depending on the diet (P<0.01) and muscle (P<0.001). The percentage of MG relative to MG+PG varied between muscles (46%, 50% and 57% for the ST, LTL and SM). The concentration and form of available glycogen at slaughter did not influence the response to electrical stimulation after adjusting for pre stimulation pH (P<0.01). The DeltapH varied significantly between muscles (0.39+/ 0.03, 0.26+/-0.02 and 0.20+/-0.03 for the ST, LTL and SM) after adjusting for pre stimulation pH. Differences in the temperature adjusted rate of pH decline were observed between the muscles (LTL>SM>ST). Importantly, a positive linear association (P=0.05) was found between muscle glycogen(A) concentration at slaughter and the rate of pH decline (temperature adjusted). PMID- 22062272 TI - Utilization of interesterified oil blends in the production of frankfurters. AB - Ten treatments of frankfurters were produced with interesterified oil and oil blends (palm oil, palm stearin, cottonseed oil, hazelnut oil and their mixtures) and were compared to control, produced with all animal fat. Addition of interesterified oil and oil blends affected (p<0.05) the moisture and fat content and pH values of frankfurters. According to the colour measurements, the brightness value (L(*)) of most of the samples with interesterified oil and oil blends were higher (p<0.05) than the control. The fatty acid composition of frankfurters was modified. The PUFA/SFA values of frankfurters were increased due to the presence of interesterified oil and oil blends in the formulation. Frankfurters with 100% interesterified cottonseed oil or with interesterified oil blends with 66.6% and 83.4% cottonseed oil had PUFA/SFA ratio higher than 0.4 and are considered better than all others from the health point of view. Frankfurters produced with 100% interesterified cottonseed and hazelnut oil or with interesterified hazelnut oil blends had the same (p>0.05) scores for sensory attributes with the control, while all other treatments were also acceptable. PMID- 22062273 TI - The use of visible and near infrared reflectance spectroscopy to predict beef M. longissimus thoracis et lumborum quality attributes. AB - Visible and near infrared reflectance spectroscopy was used to predict pH at 24h (pH24) post-mortem, sarcomere length (SL), cooking loss (CL), Warner-Bratzler Shear Force (WBSF) and colour parameters (L(*), a(*), b(*)) in beef cattle samples. Samples from M. longissimus thoracis et lumborum from 30 bulls were aged at 4 degrees C for 1, 3, 7 and 14 days and analysed for pH, SL, CL, WBSF and colour. NIRS calibrations for pH24, luminosity at 0 (L(*)t0) and 60min (L(*)t60) showed good predictability (R(2)=0.97, 0.85 and 0.82; SECV=0.10, 1.16, 1.36, respectively), whereas those related to the rest of the parameters were poorer. PMID- 22062274 TI - Microbiological contamination of pig and cattle carcasses in different small scale Swiss abattoirs. AB - A total of 750 pig carcasses and 535 cattle carcasses from 17 small-scale abattoirs were sampled by excision at four sites (pig: neck, belly, back, ham; cattle: neck, brisket, flank, rump). Samples were examined for total viable counts (TVC) and Enterobacteriaceae. Mean TVCs ranged from 2.4 to 4.2 log(10)CFUcm(-2) on pig carcasses and from 2.7 to 3.8 log(10)CFUcm(-2) on cattle carcasses. With regard to EU Regulation (EC) No 2073/2005, TVCs were mainly considered satisfactory (pig: 81.3%; cattle: 71.4%). Amongst sites, the back (pigs) and neck (cattle) tended to yield higher TVCs. Enterobacteriaceae were detected in low counts on 23.9% of pig carcasses and 21.7% of cattle carcasses. Amongst abattoirs, Enterobacteriaceae prevalence on pig and cattle carcasses ranged from 2.0% to 56.0% and from 0.0% to 55.0%, respectively. Consequently, criteria of the EU Regulation proved to be a suitable tool for the appraisal of microbiological results (TVCs) from pig and cattle carcasses from small-scale abattoirs. Because the occurrence of Enterobacteriaceae on carcasses was too infrequent to ensure log normality, frequencies should be compared for these organisms. PMID- 22062275 TI - Association between animal, transportation, slaughterhouse practices, and meat pH in beef. AB - The objective of this study was to evaluate the influence of factors related to animal, farm, transportation, and animal handling at the slaughterhouse, as well as their interactions, on pH of beef meat. A total of 5494 cattle (343+/-45d of age) from 181 different Spanish farms were surveyed during three seasons (spring, summer, and winter) and a total of 25 pre-slaughter variables were recorded. Meat pH was measured at the Longissimus dorsi 24h post-mortem (pH(24)). After a variable selection procedure, a mixed-effects logistic regression model was conducted with 5 variables (1 random and 4 fixed) to identify the main factors, and their interactions, affecting meat pH(24). Average incidences of meat pH(24) greater than 5.8 and 6.0 were 13.89% and 4.02%, respectively. The variability of meat pH(24) explained with studied factors and their interactions was only 4.9%, a value too low to allow making technical decisions to improve meat pH(24) in the Spanish market considering the variables studied. PMID- 22062276 TI - Effect of dietary rosemary and alpha-tocopheryl acetate on the oxidative stability of raw and cooked pork following oxidized linseed oil administration. AB - The effect of a 2% dietary administration to pigs of oxidized linseed oil (targeted level of 150mEq.O(2)/kg oil after heating at 50 degrees C and exposure to air for 3-4 days following addition of 10ppm CuSO(4)), either or not in combination with antioxidants, on the oxidative stability of raw and cooked pork during illuminated chill storage was assessed. The antioxidant treatments were: 40ppm alpha-tocopheryl acetate, 40ppm rosemary extract, 40ppm rosemary extract+2ppm gallic acid, and 40ppm alpha-tocopheryl acetate+40ppm rosemary extract. A total of 20ppm of alpha-tocopheryl acetate (ATA) was added to all diets in order to meet the physiological requirement of the animals. The antioxidant treatments did not exert any effect on colour and protein oxidation. Lipid oxidation was only decreased by dietary ATA when comparing the ATA supplemented groups combined versus a control treatment group for raw but not for cooked meat. This was due to a higher content of alpha-tocopherol in the meat and subcutaneous fat. The lipid oxidation results suggested a lack of antioxidant effect for the rosemary extract. No evidence for a synergistic effect of the antioxidant combinations was observed. PMID- 22062277 TI - Prediction of the fatty acid composition of beef by near infrared transmittance spectroscopy. AB - The intramuscular fat content and composition influence consumer selection of meat products. A study predicting the fatty acid (FA) profile of ground beef from the Longissimus thoracis of yearling bulls (n=100) using near infrared transmittance spectroscopy (NIT) was conducted. The samples were scanned using an Infratec 1265 Meat Analyzer which operates in transmittance mode from 850 to 1050nm. NIT technology was able to accurately predict (R(CV)(2) over 0.76) some prominent FAs such as C14:0, C16:0, C16:1cis9, C17:0, C18:1cis9 and C18:1cis11, and minor FAs like C13:0, C15:0, C17:1cis9 and C18:1cis13. When studying FA groups, NIT spectra were able to accurately predict saturated (R(CV)(2)=0.837), branched (R(CV)(2)=0.701) and monounsaturated (R(CV)(2)=0.852) FAs. In addition, NIT spectra provided useful information on the contents of conjugated linoleic acids (CLA) in beef. These results show the potential of NIT technique as a rapid and easy tool to predict the major FAs in beef, especially those located in triglycerides. PMID- 22062278 TI - Effects of breed and a concentrate or grass silage diet on beef quality in cattle of 3 ages. I: Animal performance, carcass quality and muscle fatty acid composition. AB - An increase in the intake of the n-3 series polyunsaturated fatty acids (PUFA) is recommended by nutritionists for the human diet and beef is a significant source of these fatty acids. Enhancing the n-3 PUFA content of beef is important in view of the generally saturated nature of fatty acids in ruminant meats and the potentially negative effect this can have on human health. This study examined the effects of breed and diet on the fatty acid composition of beef M. longissimus. Ninety-six steers were used, 48 Aberdeen Angus cross (AA) and 48 Holstein-Friesian (HF). At 6months of age, 3 groups were identified, to be slaughtered at 14, 19 and 24months, respectively. Each group consisted of eight steers of each breed fed on a concentrate or a grass silage diet, rich in n-6 and n-3 PUFA, respectively. The intake of the concentrate diet was restricted so that steers of each breed grew at a similar rate on each diet. The early maturing AA produced heavier, fatter carcasses with better conformation. Animals fed grass silage had higher carcass fatness and conformation scores and higher levels of neutral lipid and total lipid in muscle than those fed concentrate. When all animals were pooled, a decline in PUFA% as total muscle lipid increased was evident. Feeding a grass silage diet rich in alpha-linolenic acid (18:3n-3) increased levels of this fatty acid in muscle neutral lipid by a factor of about 3.0 compared with the concentrate diet, as well as enhancing the synthesis of the n-3 series long-chain C20-22 PUFA in the phospholipid fraction, including docosahexaenoic acid (DHA, 22:6n-3). In contrast, both levels and proportions of linoleic acid (18:2n-6) and the n-6 series C20-22 PUFA were higher in animals fed the concentrate diet. The proportions of 18:1trans and conjugated linoleic acid (CLA) in muscle neutral lipid were higher in animals fed concentrate compared with silage in all 3 groups. This was partly due to increased consumption of 18:2n-6. The ratio of PUFA to saturated fatty acids (P:S) in muscle was reduced by feeding grass silage, partly as the result of increased fat deposition. However, the increase in levels of n-3 series fatty acids with silage-feeding resulted in beneficially low n-6:n-3 ratios in muscle in all age groups (approximately 1.2 compared with 12.0 in the concentrate diet). Subtle breed differences in PUFA amounts and proportions were noted. Holstein-Friesians had higher proportions of PUFA and higher P:S ratios compared with AA, partly due to a higher proportion of phospholipid in total lipid. In phospholipid itself, HF in the 19 and 24months groups had higher proportions of most n-3 PUFA. In all age groups the ratio of DHA to its precursor, 18:3n-3 was higher in HF. PMID- 22062279 TI - Effects of breed and a concentrate or grass silage diet on beef quality in cattle of 3 ages. II: Meat stability and flavour. AB - This study examined the effect of breed and diet on meat quality, defined as lipid stability, colour shelf life and sensory quality. Ninety-six steers were used, half Aberdeen Angus (AA) cross and half Holstein-Friesian (HF). They were reared from 6 months of age on a standard concentrate diet or grass silage and slaughtered at 14, 19 or 24 months of age. Breed had small effects on quality with lower lipid stability in muscle of 24 month-old HF (P<0.05). Sensory scores were similar between the breeds, the few differences being in favour of AA. Diet had the biggest effects on meat quality, in all 3 age groups. The grass silage diet produced higher plasma and muscle levels of vitamin E, lower lipid oxidation in loin steaks measured at 4 and 7 days of retail display and better colour stability (saturation) during shelf life in MAP (O(2):CO(2); 75:25) (all P<0.001). The high values for lipid oxidation in the concentrate-fed steers were linked to high muscle PUFA concentrations and low levels of vitamin E. PMID- 22062280 TI - Effect of stunning systems on meat quality of Manchego suckling lamb packed under modified atmospheres. AB - The effects of the type of stunning (TS) [electrically vs. gas] and packing in modified atmospheres (MA) [MA-A: 30% CO(2)/70% O(2); MA-B: 30% CO(2)/69.3% N(2)/0.7% CO; MA-C: 40% CO(2)/60% N(2)] on meat quality (pH), drip losses (DL), water holding capacity (WHC), shear force (SF) and instrumental colour (L(*), and C(*)chroma) of suckling lamb of the Spanish Manchego breed at 7, 14 and 21d post packing was studied. Acceptance of meat samples (on the basis of colour and odour) was determined. In general neither the TS nor the MA affected the pH values. Meat from the gas stunned lambs had the lowest DL (P<0.001 at 14d post packing), but lower WHC (more water expelled; P<0.01 at 14 and 21d post-packing), was more tender (P<0.01) and had higher L(*) (P<0.001 at 14d post-packing) and C(*) values (P<0.001) than the electrically stunned group. Similar values of WHC and SF were observed for all MA types but the use of CO in the packs (MA-B) caused less DL, gave the highest C(*) values, acceptability and colour stability with time of storage. PMID- 22062281 TI - Effects of Urtica dioica and Hibiscus sabdariffa on the quality and safety of sucuk (Turkish dry-fermented sausage). AB - In this study, the effect of Urtica dioica, Hibiscus sabdariffa butylatedhydroxytoluene (BHT) and nitrite/nitrate on the quality (pH, Hunter L-, a- and b-value and sensory attributes) and safety [2-thiobarbituric acid reactive substances (TBARS) value and biogenic amine] were investigated during the ripening periods of sucuk (Turkish dry-fermented sausage). During the first 2 days of ripening, pH values decreased (P<0.05) rapidly from 5.78 to about 4.49. pH values of batters were not significantly (P<0.05) affected by the addition of nitrite/nitrate, BHT, U. dioica, H. sabdariffa. TBARS values increased from 0.52 to about 0.95mg/kg significantly (P<0.05) during the first 4 days in control, and H. sabdariffa added batters. The highest (P<0.05) histamine concentration was determined in the control batter prepared without antioxidant. U. dioica was more effective (P<0.05) on decreasing histamine and putrescine concentration than the other antioxidants. Putrescine concentration in batters increased (P<0.05) from 1.13 to about 15.34mg/kg during the first 4 days. Tyramine concentration increased significantly (P<0.05) during the ripening period from 5.55 to 103.93mg/kg. The control batter had the highest (P<0.05) tyramine concentration about 50.21mg/kg. Hunter L-values were not affected (P>0.05) from ripening time and addition of antioxidants into batter. The Hunter a-value increased (P<0.05) during the ripening periods, however, b-values decreased (P<0.05) from 12.58 to about 10.53. Overall sensory quality evaluated from color, flavor and ease of cutting scores increased (P<0.05) from 3.25 to about 9.00. PMID- 22062282 TI - Muscle proteome and meat eating qualities of Longissimus thoracis of "Blonde d'Aquitaine" young bulls: A central role of HSP27 isoforms. AB - Longissimus thoracis (LT) of 10 Blonde d'Aquitaine young bulls were sampled at slaughter. Protein composition of fresh muscle and of meat aged for 14 days was investigated by two-dimensional electrophoresis. Cooked meat properties were also evaluated by sensory analysis. When searching for early predictors of tenderness, abundance of succinate dehydrogenase (SDH) was the best common predictor of initial and overall tenderness, explaining 65.6% and 57.8% of variation of these palatability traits. Study of the evolution of the protein content during ageing allowed to identify targets of postmortem proteolysis. They were mainly structural (actin, MyBPH) and chaperone (HSP27, alpha-crystallin) proteins. Furthermore, in a regression analysis modelling sensory tenderness, levels of HSP27 in fresh muscle and levels of HSP27 fragments in aged meat explained up to 91% of variation in sensory scores. Data suggest the existence of an underlying HSP27-related cellular mechanism, with consequences on tenderness development. PMID- 22062283 TI - Determination of phospholipid molecular species in pork meat by high performance liquid chromatography-tandem mass spectrometry and evaporative light scattering detection. AB - Normal phase high performance liquid chromatography has been optimized for both evaporative light scattering detection and tandem mass spectrometry in order to characterize the natural phospholipids (PL) (classes and molecular species) of raw and cooked pork meat. The PL fraction included phosphatidylcholine (PC) (42.9%+/-4.5 for raw vs 42.6%+/-8.0 for cooked meat), plasmalogen phosphatidylethanolamine (pPE) and phosphatidylethanolamine (PE) (26.7%+/-3.1 vs 28.5%+/-2.3), cardiolipin (CL) (8.3%+/-2.9 vs 6.3%+/-0.7), sphingomyelin (Sph) (7.5%+/-0.9 vs 8.3%+/-2.1), phosphatidylinositol (PI) (6.8%+/-0.7 vs 6.5%+/-2.1) phosphatidylserine (PS) (4.9%+/-0.5 vs 4.6%+/-1.4) and lysophosphatidylcholine (LPC) (2.9%+/-1.3 vs 3.3%+/-2.6). Arachidonic acid (absent in Sph) was mainly present in pPE and PI and formed molecular species with a saturated fatty acid, such as stearic (as in PI, PS, PE and PC) or palmitic acid (as in PE and PC), or the respective vinyl ethers in pPE (p18:0 and p16:0); however, in PC, arachidonic acid also formed combinations with oleic and linoleic acid. Palmitic acid formed the most abundant molecular species in PC, but not in CL, PE, PI and PS. Unexpectedly, the cooked pork meat showed an increased content of the molecular species of PI and LPC with more unsaturated fatty acids (18:0/20:4 and 18:2, respectively) with respect to raw meat. PMID- 22062284 TI - Differentiation of European wild boar (Sus scrofa scrofa) and domestic swine (Sus scrofa domestica) meats by PCR analysis targeting the mitochondrial D-loop and the nuclear melanocortin receptor 1 (MC1R) genes. AB - This work describes the differentiation of European wild boar (Sus scrofa scrofa) and domestic swine (Sus scrofa domestica) meats by PCR targeting sequences from two molecular markers: the mitochondrial displacement loop (D-loop) region and the nuclear melanocortin receptor 1 (MC1R) gene. A polymorphic D-loop fragment (~270bp) was amplified and sequenced in a number of wild and domestic Sus scrofa meat samples, to find a nucleotide region suitable for PCR-RFLP analysis. Sequence data showed the presence of only a few point mutations across Sus scrofa D-loop sequences, not allowing direct discrimination between wild boar and domestic swine meats. Later, the MC1R gene was targeted and Sus scrofa-specific primers designed to amplify a 795bp MC1R fragment. Subsequent RFLP analysis of the MC1R swine-specific amplicons allowed selection of BspHI and BstUI endonucleases to carry out intraspecific Sus scrofa differentiation. Digestion of MC1R amplicons with the chosen enzymes generated characteristic PCR-RFLP profiles that allowed discrimination among meats from wild and domestic swine specimens. The technique also enabled the detection of samples that yielded heterozygous profiles, suggesting hybrids resulting from wild boar and domestic pig breeding. The PCR-RFLP reported here, targeting the MC1R gene may be routinely applied to verify the correct labelling of game products. PMID- 22062285 TI - Compound C, an inhibitor of AMP-activated protein kinase, inhibits glycolysis in mouse longissimus dorsi postmortem. AB - Pale, soft, and exudative (PSE) meat has been recognized for decades and causes huge economic loss to the meat industry due to its inferior quality. Although it has been well established that fast and excessive glycolysis combined with high temperature in muscle early postmortem is the cause of PSE meat, the molecular mechanisms associated with this abnormal glycolysis remain poorly defined. Our previous studies with mice and pigs suggest that AMPK regulates muscle glycolysis postmortem. To confirm further the role of AMPK in the regulation of postmortem glycolysis, we investigated the effects of intraperitoneal injection of compound C, a specific AMPK inhibitor, on AMPK activation and glycolysis in postmortem longissimus dorsi (LD) muscle of mice. Data showed that intraperitoneal injection of compound C inhibited AMPK activation in postmortem mouse LD muscle. Simultaneously, injection of compound C inhibited glycolysis and increased muscle pH corroborating of our previous observations that postmortem glycolysis is inhibited in AMPK knockout mice. This study firmly supports that AMPK regulates glycolysis in postmortem skeletal muscle and suggests that AMPK can be a target to control postmortem glycolysis, preventing incidence of PSE meat. PMID- 22062286 TI - Changes in l-carnitine content of fish and meat during domestic cooking. AB - Human adults store around 20g of l-carnitine. In the human body, l-carnitine is not metabolized but excreted through the kidney. Lost l-carnitine has to be replenished either by a biosynthetic mechanism or by the consumption of foods containing l-carnitine. Today, there is no "official" recommended daily allowance for l-carnitine but the daily need for l-carnitine intake has been estimated in the wide range of 2-12MUmol/day/kg body weight for an adult human. In this study we evaluated the effect of freezing and of different cooking methods on the l carnitine content of red meat and fish. l-carnitine was abundantly present in all beef products analyzed. The amounts in the various cuts were similar and our data showed that freezing or cooking did not modify l-carnitine content. Salmon contained about 12 times less l-carnitine than beef but except in smoked salmon, cooking or freezing did not alter l-carnitine content. This study confirms the important role that meet products play for providing adequate amount of l carnitine to the human body. PMID- 22062287 TI - Quantification of zinc-porphyrin in dry-cured ham products by spectroscopic methods Comparison of absorption, fluorescence and X-ray fluorescence spectroscopy. AB - Zinc-protoporphyrin (Zn-pp), which has been identified as the major pigment in certain dry-cured meat products, was extracted with acetone/water (75%) and isolated from the following meat products: Parma ham, Iberian ham and dry-cured ham with added nitrite. The quantification of Zn-pp by electron absorption, fluorescence and X-ray fluorescence (XRF) spectroscopy was compared (concentration range used [Zn-pp]=0.8-9.7MUM). All three hams were found to contain Zn-pp, and the results show no significant difference among the content of Zn-pp quantified by fluorescence, absorbance and X-ray fluorescence spectroscopy for Parma ham and Iberian ham. All three methods can be used for quantification of Zn-pp in acetone/water extracts of different ham types if the content is higher than 1.0ppm. For dry-cured ham with added nitrite, XRF was not applicable due to the low content of Zn-pp (<0.1ppm). In addition, XRF spectroscopy provides further information regarding other trace elements and can therefore be advantageous in this aspect. This study also focused on XRF determination of Fe in the extracts and as no detectable Fe was found in the three types of ham extracts investigated (limit of detection; Fe?1.8ppm), it allows the conclusion that iron containing pigments, e.g., heme, do not contribute to the noticeable red colour observed in some of the extracts. PMID- 22062288 TI - Effect of breed and ageing time on meat quality and sensory attributes of veal calves of the "Ternera de Aliste" Quality Label. AB - The effect of breed, sex and ageing time on carcass, meat and eating quality were examined in 32 calves of the "Ternera de Aliste" Spanish Quality Label. Swiss Brown*Alistano-Sanabresa heifers were mated with Charolais or Limousin bulls in order to study the effect of breed. Bull and heifer calves were slaughtered when they were 6-7 months old. Samples of the M. longissimus dorsi were aged for 3, 5 or 7 days and chemical and sensory analyses were done. The results showed no differences due to sex but Charolais sires produced meat which was more tender, juicier and had more odour intensity with a darker colour than meat of the Limousin sired animals. Ageing influenced both sensory and instrumental hardness, colour and odour intensity. After seven days of maturation the meat from such young animals achieved a high quality. PMID- 22062289 TI - Effects of electrical stimulation, chilling temperature and hot-boning on the tenderness of bovine muscles. AB - The objective of this study was to determine the effects of hot-boning, low voltage electrical stimulation (ES) and chilling temperature on the tenderness of bovine M. longissimus dorsi (LD) and M. semimembranosus (SM) muscles. LD (n=32) and SM (n=32) muscles were subjected to different post-mortem treatments; hot boning (before 90min post-mortem), cold-boning (at 48h post-mortem), low voltage ES and rapid or slow chilling. Hot-boned muscles which were not electrically stimulated (NES) had higher Warner Bratzler shear force (WBSF) values (P<0.001) and shorter sarcomeres (P<0.001) than cold-boned muscles. Hot-boned muscles subjected to ES had lower pH values (P<0.001) post-stimulation and up to 8h post mortem than NES muscles. At both chilling temperatures WBSF values were lower in ES hot-boned LD and SM muscles at days 2, 7 and 14 post-mortem than NES muscles. Hot-boned muscles subjected to slow chilling had longer sarcomeres (P<0.001) than those subjected to fast chilling. In hot-boned SM muscles, ES resulted in longer sarcomere lengths (P<0.001). However, ES did not have a significant effect on the sarcomere length of LD muscles. As indicated by WBSF values all muscles tenderised during ageing, including muscles which were 'cold shortened'. Proteolysis was not the main reason for differences in WBSF values between ES and NES muscles as judged by qualitative sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). A combination of slow chilling and ES had a positive effect on hot-boned muscles with respect to WBSF values. PMID- 22062290 TI - Manipulation of the pre-rigor phase to investigate the significance of proteolysis and sarcomere length in determining the tenderness of bovine M. longissimus dorsi. AB - The objective of this study was to evaluate the importance of proteolysis and sarcomere length in determining the tenderness of bovine M. longissimus dorsi (LD) muscle over a 21-day period. This was done by altering the pre-rigor glycolytic behaviour of hot-boned LD muscles using different early post-mortem temperature regimes. Hot-boned LD muscles (n=8) were cut in two, randomised, placed in polythene bags and submerged in a water bath set at 5 degrees C (rapidly chilled) and 15 degrees C (slowly chilled) for 8h post-mortem. All muscles were then stored at 2 degrees C for up to 21 days post-mortem. The temperature regimes altered the glycolytic behaviour of the muscles in the pre rigor period. The slowly chilled muscles exhibited a faster (P<0.01) pH fall than rapidly chilled muscles. Cold shortening was induced in rapidly chilled muscles as they had shorter (P<0.01) sarcomere lengths than slowly chilled muscles up to day 21 post-mortem. Warner Bratzler shear force values (WBSF) deemed cold shortened muscles as tougher than noncold shortened up to day 14 post-mortem. Both cold-shortened and noncold-shortened muscles tenderised over time to an extent where there was no significant difference in WBSF values by day 21 post mortem. SDS-PAGE protein profiles indicated that the rate of proteolysis was faster in slowly chilled muscles when compared to rapidly chilled muscles. However by day 21 post-mortem it appeared that rapidly and slowly chilled muscles underwent proteolysis to the same extent. PMID- 22062291 TI - Nutritional characteristics of veal from weaned and unweaned calves: Discriminatory ability of the fat profile. AB - The chemical and nutritional composition of the Longissimus thoracis muscle from 58 'Rubia Gallega' breed animals was measured to differentiate veal of weaned from unweaned calves. Fat, protein, ash, and moisture contents of muscle were determined by near infrared reflectance spectroscopy (NIRS) and the fatty acid (FA) profiles were determined by gas chromatography. Calves suckled their mothers at pasture followed by an indoor period. The weaned group was finished on concentrates indoors, whereas the unweaned group was continued suckling with a complementary concentrate diet, also indoors. The unweaned group had higher total FA (p<0.001), monounsaturated (MUFA) (p<0.05) and polyunsaturated (PUFA) (p<0.05) FA contents, lower saturated FA (SFA) (p<0.01) concentration, and a higher PUFA:SFA ratio (p<0.05) than the weaned group. A multivariate step discriminant procedure selected nine variables out of 38 tested from the FA profile. The SFA fraction lower than C11 followed by the margaric FA and the n-6:n-3 PUFA ratio were the most discriminating variables for separating the weaning classes, regardless of the gender. Calibration and cross-validation misclassification errors were 0% and 1.67%, respectively. A more powerful discriminant function was estimated for males only, where the SFA fraction lower than C11 followed by tricosanoic, and margaric FA were the most discriminant, with zero misclassification errors. PMID- 22062292 TI - Ruminant fat volatiles as affected by diet. A review. AB - Volatile compounds in meat have been widely studied for their favourable or undesirable effects on meat flavour, or for their potential use in tracing the animal feeding system. To date, the chemical mechanisms causing the appearance of volatile compounds in meat have been largely understood. Several variables are involved in the accumulation of volatiles in animal tissues and among them animal diet plays a key role. The purpose of the present review is to highlight the effects of different dietary regimes (concentrate, green grass and fat-enriched diets) on the appearance of fat volatile compounds in ruminant meat. Grain-based diets induce greater accumulations in meat of branched-chain fatty acids, some aldehydes, and lactones while meat fat from grazing animals contains high levels of phenols, terpenes, indoles and sulphur compounds. Fat-enriched diets exert their effect mainly on those volatiles which originate from polyunsaturated fatty acids. Cooking procedures have been considered for their contribution to fat volatiles in meat by reactions induced by high temperatures. PMID- 22062293 TI - The effect of spineless cactus (Opuntia ficus-indica f. inermis) supplementation on growth, carcass, meat quality and fatty acid composition of male goat kids. AB - The objective of this study was to determine the effects of grain compared to spineless cactus feeding on goat kids growth, carcass characteristics and FA profile. For this purpose, 21 kids were used and allocated to 3 groups receiving a low quantity (200g) of oat hay. The control group received ad libitum a concentrate containing 130g crude protein (CP) per kg of dry matter (C130). The second group received half of that contained consumed by the control one but its CP content was 260g/kg DM and spineless cactus ad libitum (C260-Cac). In the third group, concentrate intake was limited to soya bean at a quantity that provided the same CP quantity as the two other groups and also cached spineless cactus was distributed ad libitum (Soya-Cac). Animals of all groups had free access to water. At the end of the growth trial which lasted for 74 days, all kids were slaughtered. Samples of longissimus dorsi muscle were used for meat quality and FA composition study. Animals in the control group and those in the C260-Cac had higher growth rate than Soya-Cac diet animals. Muscle and adipose tissue mean weights were higher in the first groups while the bone weight was similar in all treatments. Animals given Soya-Cac diet had relatively less fat (10.5%) than those fed other diets (p<0.001). Carcass fat content tended to be lower (p=0.07) in C260-Cac goats (13.5%) than in those of the C130 group (15.8%). The ultimate pH ranged between 6.18 and 6.48; it was higher in meat from control goats (C130) than in animals receiving cactus. Dietary treatment had no significant effect (p>0.05) on meat moisture, ash, crude fat and protein contents. The intra muscular lipid composition in fatty acids showed differences between the control group and those receiving cactus. Cactus in the diet was associated with more C18:2 and conjugated linoleic acid (CLA) as well as a higher proportion of PUFA and PUFA:SFA ratio than control ones. In conclusion, this study showed that cactus feeding of goat kids maximises the proportion of CLA, PUFA and PUFA:SFA ratio. PMID- 22062294 TI - Antimicrobial effects of selected plant essential oils on the growth of a Pseudomonas putida strain isolated from meat. AB - The inhibitory effect of 60 different essential oils was evaluated on a Pseudomonas putida strain of meat origin, associated with meat spoilage. Essential oils were tested at concentrations from 0.003 to 0.8% (wt/vol) to determine minimum inhibitory and maximal tolerated concentrations (MIC and MTC, respectively) using an agar medium culture. Of the 60 samples tested, Corydothymus capitatus essential oil was the most active showing a MIC of 0.025% and a MTC of 0.06%. Seven essential oils (Cinnamomum cassia, Origanum compactum, Origanum heracleoticum, Satureja hortensis, Satureja montana, Thymus vulgaris carvacroliferum, Thymus vulgaris thymoliferum) have shown a strong antimicrobial activity against P. putida with a MIC of 0.05% and a MTC ranging from 0.013% to 0.025%. Ten other oils (Cinnamomum verum (leaf and bark), Eugenia caryophyllus, Cymbopogon martinii var. motia, Cymbopogon nardus, Melaleuca linariifolia, Origanum majorana, Pimenta dioica, Thymus satureoides, Thymus serpyllum) showed a high antimicrobial activity showing a MIC ranging from 0.1% to 0.4%, while the remaining were less active showing a MIC?0.8%. PMID- 22062295 TI - Beef hide antimicrobial interventions as a means of reducing bacterial contamination. AB - This project was designed to evaluate interventions capable of reducing bacterial counts on the hide prior to opening. In Trial I, fresh beef hides (n=12) were cut into sections and assigned to serve as either clipped (hair trimmed) or non clipped sections. Sections were inoculated with a bovine fecal slurry and sampled following a water wash. Treatments (distilled water, isopropyl alcohol, 3% hydrogen peroxide, 2% l-lactic acid, 10% povidone-iodine, and 1% cetylpyridinium chloride (CPC)) were then applied to each section and the sections were sampled for enumeration of aerobic plate counts (APCs), coliforms, and Escherichia coli. Within clipped samples, 1% CPC and 3% hydrogen peroxide caused the greatest reductions in APCs (4.6 and 4.4 log(10)CFU/100-cm(2), respectively), and 1% CPC, 2% l-lactic acid, and 3% hydrogen peroxide caused the greatest reductions in coliform counts (4.5, 4.1, and 3.9 log(10)CFU/100-cm(2), respectively). In Trial II, beef carcasses with hides on were sampled initially and clipped, and then 2% l-lactic acid, 3% hydrogen peroxide, or 1% CPC were applied before sampling. For APCs, 1% CPC produced the greatest reduction on the hide surface (3.8 log(10)CFU/100-cm(2)). Selective application of these antimicrobials to clipped hide opening sites reduced bacterial counts on hide surfaces, and therefore could reduce final carcass counts in these areas by decreasing the bacterial load before opening. PMID- 22062296 TI - The use of dual-energy X-ray absorptiometry to estimate the dissected composition of lamb carcasses. AB - A total of 140 male and female Dorset and Suffolk lambs were slaughtered according to four live weight classes (36-39kg, 41-44kg, 46-49kg and 51-54kg). Total tissue, fat and lean masses, and bone mineral content measured by dual energy X-ray absorptiometry (DXA) were used to predict dissected tissue weights. The DXA total weights accurately predict half-carcasses and primal cuts weights (shoulder, leg, loin and flank) (R(2)>0.99, CVe<1.3%). The prediction of the half carcass dissected fat percentage is weaker (R(2)=0.77, CVe=10.4%). Fatness prediction accuracy is equivalent for the shoulder, leg and loin (R(2) between 0.68 and 0.78, CVe between 10% and 13%). The R(2) obtained when predicting dissected lean content from DXA variables is 0.93 for the half-carcass and higher than 0.83 for all cuts other than flank (CVe are between 3.5% and 6.5%, except for the flank, which is 9.1%). The prediction of bone weight using the bone mineral content is not very accurate for the half-carcass, shoulder and leg (R(2): 0.48, 0.47 and 0.43; CVe: 10.2%, 12.0% and 11.6%, respectively). The situation improves, however, for the loin (R(2)=0.70, CVe=10.7%). In conclusion, DXA is an effective technology for predicting total weight and the amount of lean and fat in lamb carcasses and their primal cuts. PMID- 22062297 TI - Factors influencing proportion and composition of CLA in beef. AB - Bovine meat is criticised for the bad nutritional image of its lipids and fatty acids. However, with dairy products, beef is the major source of conjugated linoleic acid (CLA) which could have several human health benefits. The present study compared, from data of five nutritional experiments on bovine animals performed by the laboratory, the impact of factors linked to the animals (breed, age, sex, type of muscle) and to feeding conditions (basal diet, lipid supplements) on the CLA proportion and composition in muscles. Among these factors, linseed supplementation was an efficient way to increase CLA proportion in beef (+22% to +36%) but was highly modulated by the nature of the basal diet, and by intrinsic factors (breed, age/sex, type of muscle) since these ones could modulate CLA proportion in beef from 24% to 47%. Moreover, these factors modified also the proportion of cis,trans-CLA, related to cis,cis- and trans,trans isomers. Specific biological properties of these latter isomers should be determine to understand the consequences of intramuscular CLA isomer variations for the health of consumers. PMID- 22062298 TI - Stability of linseed oil and antioxidants containing dry fermented sausages: A study of the lipid fraction during different storage conditions. AB - Different packaging conditions (aerobic, vacuum and modified atmosphere) were evaluated in order to study the stability of the lipid fraction of dry fermented sausages manufactured with a partial substitution of pork backfat by linseed oil and antioxidants. After 5 months of storage, alpha-linolenic acid was better preserved by vacuum and MAP (7.32 and 7.74g/100g fatty acids, respectively) than in aerobic conditions (6.15g/100g fatty acids), without significant differences to values obtained after 2 months of storage for this acid. At the end of the storage, (n-6)/(n-3) fraction in sausages with linseed oil was in all cases lower than 3, in contrast to values obtained for control products that were all higher than 15. Better PUFA/SFA ratios were also observed in modified sausages (0.6 0.7g/100g fatty acids) than control ones (0.3-0.4g/100g fatty acids). No signs of lipid oxidation measured by TBARs and peroxides were detected for modified sausages regardless the packaging system used (TBARs values lower than 0.25ppm and peroxides lower than 4meq O(2)/kg), pointing at a high effectiveness of the antioxidants. Furthermore, vacuum and MAP prevented 2,4-decadienal formation. Nutritional benefits of linseed oil and antioxidants containing products were maintained after 5 months of storage. PMID- 22062299 TI - Effects of peanut skin extract on quality and storage stability of beef products. AB - Peanut skins are a low-value byproduct of peanut processing operations. They have been found to contain significant levels of natural antioxidants, but their antioxidant activity in muscle foods is unknown. The effects of peanut skin extracts on oxidation (TBARS) and color (CIE L(*)a(*)b(*)) was studied in ground beef and ground beef with added salt, phosphate (STP) and nitrite/erythorbate. Cooking loss, microbial growth, aroma acceptability and texture were also examined. The most significant reduction in oxidation was in ground beef or samples with salt, followed by phosphate (STP) or nitrite/erythorbate. Because of their low effective concentrations (200ppm), the extracts did not cause color change (P>0.05) of the products indicated by CIE L(*)a(*)b(*) value. The extracts had no effect (P>0.05) on sensory aroma. The phenolic extract from peanut skin had no effect (P>0.05) on the cooking loss of the ground beef as well as the cured and uncured formulated products. The microbial growth in fresh ground beef was not affected (P<0.05) by the phenolic extract. PMID- 22062300 TI - Preserving pre-rigor meat functionality for beef patty production. AB - Three methods were examined for preserving pre-rigor meat functionality in beef patties. Hot-boned semimembranosus muscles were processed as follows: (1) pre rigor ground, salted, patties immediately cooked; (2) pre-rigor ground, salted and stored overnight; (3) pre-rigor injected with brine; and (4) post-rigor ground and salted. Raw patties contained 60% lean beef, 19.7% beef fat trim, 1.7% NaCl, 3.6% starch, and 15% water. Pre-rigor processing occurred at 3-3.5h postmortem. Patties made from pre-rigor ground meat had higher pH values; greater protein solubility; firmer, more cohesive, and chewier texture; and substantially lower cooking losses than the other treatments. Addition of salt was sufficient to reduce the rate and extent of glycolysis. Brine injection of intact pre-rigor muscles resulted in some preservation of the functional properties but not as pronounced as with salt addition to pre-rigor ground meat. PMID- 22062301 TI - Quality characteristics of ostrich (Struthio camelus) burgers. AB - Quality characteristics and storage stability of three types of burgers prepared with ostrich meat (alone or mixed with pork or beef meat) were evaluated. Burger evaluation was based on chemical, microbiological, textural, colour, sensory and oxidation characteristics. All of the assayed formulas showed acceptable general quality scores in the sensory evaluation, but the burgers formulated with 100% ostrich meat or mixing ostrich and beef meat had the highest scores. Only TBA values and redness were influenced by storage time. Burgers formulated with ostrich and pork meat had a faster oxidation rate and became more oxidized than the others. Microbial counts indicated that, at the end of the refrigerated storage (9days), all of the preparations were spoiled. PMID- 22062302 TI - Pre-slaughter stress arising from on-farm handling and its interactions with electrical stimulation on tenderness of lambs. AB - The effect of electrical stimulation of lamb carcasses (n=269) or its absence (n=257) on shear force of m. longissimus thoracis et lumborum (LT) was monitored during ageing in pasture-fed merino lambs (n=526). The lambs were slaughtered on four different days allowing durations of between one to 10 days of recovery from pre-slaughter handling (yarding, weighing and crutching) that affected ultimate pH (pH(u)). The right LT was removed 20-40min post-slaughter, tightly-wrapped in cling film (prevents the muscle cross-section increasing and thus minimising shortening) and rapidly cooled to 15 degrees C to enter rigor mortis and age. At 0, 4, 24 and 72h post-slaughter, pH measurements and samples for shear force measurement were taken. Pre-slaughter handling had a significant negative effect on pH(u) and several days recovery were required for pH(u) to reach values associated with optimal meat quality as reflected by pH(u). Lambs with one and three days recovery (no significant difference between them) had a pH(u)>5.7 in 50% of the muscles and 19.4%>pH(u) 5.8. Whereas, in lambs with 8-10 days recovery (no significant difference between them), only 8% had a pH(u)>5.7 and 3.1%>pH(u) 5.8. Within each slaughter day electrically stimulated lambs were always more tender than non-stimulated lambs. For non-stimulated muscles at 72h, shear force values >40N occurred for 11.2% of the muscles: for electrically stimulated muscles at 72h, shear force values >40N occurred for 1.9% of the muscles. The rates of tenderisation were slower for intermediate pH(u) values resulting in higher shear force values at all ageing durations. With ageing at 72h for intermediate pH(u), non-stimulated muscles (n=38) 17.64% were >40N and for stimulated muscles (n=34), 7.9% were >40N. PMID- 22062303 TI - Lamb meat quality as affected by a natural or artificial milk feeding regime. AB - Fourteen Barbaresca lambs were divided into two groups of seven at 24h from birth and reared exclusively on natural milk (NR) or on artificial milk (AR). Lambs were slaughtered at 40 days of age. The NR group tended (P<0.10) to grow faster, thus resulting in a higher (P<0.10) carcass weight as compared to the AR group. AR meat was darker (P<0.05), leaner (P<0.001) and with a higher moisture (P<0.10) and ash (P<0.05) content than its counterpart. The proportion of polyunsaturated fatty acids was higher (P<0.01), while that of saturated lower (P<0.01) in meat from the AR group, resulting in a higher (P<0.01) polyunsaturated/saturated ratio. Linoleic acid content (P<0.001) and its n-6 series derivatives, except 9 12 trans C18:2 n-6 (P<0.001), increased more in the AR group meat than in the NR group. On the other hand, alpha-linolenic (P<0.001) and other n-3 series fatty acids were higher in meat from the NR group than in the AR group, leading to a lower (P<0.001) n-6/n-3 ratio. Furthermore, 9 cis 11 trans CLA was higher (P<0.001) in NR meat compared to AR meat. Finally, a milk-feeding regime exclusively based on artificial milk adversely affected the dietetic value of lamb meat compared to a natural rearing system, reducing the level of desirable fatty acids such as n-3 series and CLA. PMID- 22062304 TI - Composition, sensory and shelf life stability analyses of Longissimus dorsi muscle from steers reared under organic and conventional production systems. AB - In recent years the demand for organically grown food has increased. In this study, organic (O, n=6) and conventionally (C, n=6) reared steers aged between 18 and 24 months were slaughtered during the month of September 2002. Four days post slaughter, the Longissimus dorsi (LD) muscle was excised from the left side of each carcass. All muscles were vacuum packed and aged in a chill for a further seven days. Steaks were cut from each sample, and from these, lean meat was removed, blended and compositional analysis was carried out. O samples were significantly higher (P>0.05) in fat content and therefore were significantly (P>0.05) lower in moisture content than C samples. No significant differences were observed between C and O samples for protein, ash, beta-carotene, alpha tocopherol or retinol. There was also no significant difference in fatty acid content between C and O samples. Colour stability and fat oxidative stability of samples were also measured, while stored under retail conditions. Samples were packed using both modified atmosphere packaging (MAP) and by overwrapping with cling film. MAP C samples had the best colour stability while overwrapped C samples had the best lipid stability. Therefore, colour and lipid stability of beef samples were influenced by sample composition and packaging format used, which resulted in C samples outperforming O samples with respect to shelf life stability. PMID- 22062305 TI - Composition and estimation of intramuscular and subcutaneous fatty acid composition in Spanish young bulls. AB - Sixty Pirenaica yearling intact bulls were raised and slaughtered at 519+/-50kg live weight and 371+/-18 days of age. Fatty acid composition of intramuscular lipids in longissimus dorsi muscle and subcutaneous fat were determined by capillary gas chromatography. Carcass conformation and fatness, carcass weight, ether extractable intramuscular fat percentage, marbling, dorsal fat thickness, and ultrasonic parameters were recorded to study the relationship between these traits and fatty acid profile. Lipids of subcutaneous adipose tissue had higher monounsaturated fatty acids (MUFA) percentage (49% vs. 33%) but lower saturated fatty acids (SFA) (51% vs. 46%) and polyunsaturated fatty acids (PUFA) (16% vs. 5%) percentages than intramuscular fat depots (p<0.001). Fatter carcasses had higher MUFA percentage and lower PUFA percentage (p<0.01) in intramuscular fat. Carcass weight and conformation would contribute to explain the fatty acid profile of subcutaneous fat (p<0.05). Ultrasound readings reflected the effect of fatness on fat composition. PMID- 22062306 TI - Changes in proteolytic enzyme mRNAs relevant for meat quality during myogenesis of primary porcine satellite cells. AB - The objective was to study the regulation of proteolytic enzyme mRNA's in porcine satellite cells during proliferation and differentiation. Beyond 80% confluence, cells were grown in absence or presence of 1MUM insulin. The temporal changes in transcription of micro molar-, milli molar- and muscle specific calpains (p94), calpastatin and caspase 3 in response to insulin was evaluated and myogenin transcription and creatine kinase activity was determined to indicate differentiation. The housekeeping genes (GAPDH and beta-actin) were slightly affected by developmental stage and transiently by the insulin treatment but this did not affect the conclusions. The mRNA abundance of micro molar calpain, p94 and calpastatin increased from proliferation to differentiation. Milli molar calpain- and caspase 3-transcriptions were up-regulated in two steps, suggesting these two enzymes are involved in two distinct processes. Insulin stimulated differentiation as indicated by elevated creatine kinase activity but did not affect myogenin transcription. Insulin down-regulated milli molar calpain and calpastatin transcription and tended to down-regulate caspase 3 transcription but did not affect p94 or micro molar calpain. In conclusion, proteolytic enzymes relevant for post-mortem tenderisation are regulated at the gene level during myogenesis, indicating they are involved in muscle cell and muscle fibre development. Thus, a porcine satellite cell culture may be a model system to study regulation and relative contribution to proteolysis by the calpains. PMID- 22062307 TI - Colour and textural attributes of sucuk during ripening. AB - The sensory (flavour, colour, and ease of cutting scores), colour (Hunter L, a, b, YI, total colour difference, hue angle, chroma, and browning index values) and textural (hardness, adhesiveness, springiness, cohesiveness, gumminess, chewiness, and resilience) attributes of sucuk were followed during the ripening period. Colour scores increased (P<0.05) from score 4 to 6 during the first 3 days of the ripening period and then decreased (P<0.05). The lightness (L values), yellowness (b), and hue angle of sucuk decreased (P<0.05) during the ripening period. The major colour changes occurred between the 5th and 9th days of the ripening period. Pearson correlation test indicates that a positive relationship (P<0.01) exists between a-values and sensory colour scores. The overall sensory scores changed (P<0.05) in parallel to the flavour scores. Hardness, gumminess, and chewiness of sucuk increased (P<0.05) during the ripening period. Strong relationships (P<0.01) were found between hardness and cutting scores. Adhesiveness values of sucuk decreased significantly (P<0.05) about 10 times from -9.3 to -92.6 during the ripening period. Springiness and cohesiveness values decreased during the ripening period, but not significantly (P>0.05). Cutting scores were related (P<0.01) to gumminess (0.921) and chewiness (0.922) values but not to resilience (P>0.05). It was observed that most instrumental colour and textural attributes were in agreement with sensory attributes. These results indicated that instrumental methods could be easily adapted and can be used for evaluation of quality attributes of sucuk during the ripening period. PMID- 22062308 TI - Quality of retail beef from two grass-based production systems in comparison with conventional beef. AB - Seventy beef strip loins (Longissimus dorsi) were sampled, originating from labels prescribing pasturing (PS, suckler beef; PF, finished steers or heifers), from conventional production (CH, heifers; CB, young bulls), and from a label producing intensively fattened young bulls (LB) and prescribing specific husbandry conditions but not grazing. Samples were purchased in autumn and spring (1:1) from 33 retail stores in northeastern Switzerland. Colour was lightest in LB beef, while PS displayed the least intensive red. Shear force was low in pasture beef, with PF showing the lowest variability. Pasture beef was richer in n-3 fatty acids than beef of all other origins. The n-6/n-3 ratio was consistently below 2 in pasture beef, while it ranged above 5 in LB, and also in CH and CB when purchased in spring. Prescribing year-round feeding of grass products and the use of steers or heifers therefore guarantees n-3 enriched beef, which can be at least as tender as conventional beef. PMID- 22062309 TI - Influence of different dietary vitamin C levels on vitamin E and C content and oxidative stability in various tissues and stored m. longissimus dorsi of growing pigs. AB - Both vitamin E and C have antioxidative properties and may act synergistically. To examine a possible interaction between vitamin E, C and oxidative stability in various tissues, 40 barrows (25-105kg body weight) were allocated to four cereal based diets (13.4MJ digestible energy/kg, 168g crude protein/kg, 140mg dietary dl alpha-tocopheryl acetate) which were supplemented with 0 (B), 150 (C100), 300 (C200) or 600 (C400)mg/kg crystalline ascorbic acid. The influence of storage time on these factors in m. longissimus dorsi samples (LD) was investigated. Samples of liver (LI), heart (HT), spleen (SP), backfat outer layer (BF) and LD were obtained. Dry matter, vitamin E, vitamin C and thiobarbituric acid reactive substances (TBARS) were analyzed in all investigated tissues and in addition color (L(*), a(*), b(*) values) and drip loss measurements in LD at day 0, 1, 2, 3, 4 and 8 were collected. The treatments did not influence growth performance and slaughter data of the pigs. Neither the vitamin E nor the vitamin C content of investigated tissues showed differences due to feeding treatments. There was also a lack of response to the amount in TBARS. Parameters in LD samples were only affected by storage time and not by diets. The results show that dietary use of both vitamins simultaneously did not further improve qualitative characteristics of the investigated pork tissues. PMID- 22062310 TI - Design of a new cooked meat sausage enriched with calcium. AB - The effect of calcium lactate, calcium gluconate and calcium citrate addition on the sensory properties of cooked meat sausages has been studied. Conventional and reduced-fat products (approx. 40%) were manufactured. The calcium salts studied were added in sufficient amounts to 100g of final product to give 20% and 25% of calcium RDA (1200mg). The energy value reduction in the final products was close to 30%. The instrumental measurement of colour and texture was performed. The presence of calcium salts only slightly decrease the lightness of the sausage and few changes were observed in relation to the texture. These were mainly related to increased hardness, observed at levels of calcium at 25% RDA. Sensory properties were estimated by a hedonic test. In general terms, they were very acceptable, which indicated that it is possible to manufacture conventional and reduced-fat cooked meat products enriched with calcium as a new healthier meat product. PMID- 22062311 TI - The effect of a muscle-glycogen-reducing finishing diet on porcine meat and fat colour. AB - The objective of the present study was to elucidate the significance of a muscle glycogen-reducing finishing diet containing a high ratio of rapeseed and grass meal on fat colour and pork colour compared with a control diet. Pork colour was determined as the extent of blooming of M. longissimus dorsi (LD) and M. semimembranosus (SM) after 1, 2, 4, 8 and 15 days of aging, while fat colour was measured on back fat and stripped bacon the day after slaughter. The muscle glycogen-reducing diet significantly decreased the glycogen content measured 1min after slaughter in LD. This was reflected as decrease in early post-mortem temperature, as well as a tendency to higher initial pH in both muscles. Moreover ultimate pH was significantly higher in LD from strategically fed pigs compared to the control group and the same tendency was found in SM. Independent of muscle and time of aging, the colour of bloomed pork from pigs fed the control diet had higher chroma and L(*), a(*) and b(*) values compared with pork from the pigs fed the muscle-glycogen-reducing diet with the effect being most pronounced in LD. This can be explained by the slightly higher pH(45min) in the muscles from the pigs fed the muscle-glycogen-reducing finishing diet, which sustain the metmyoglobin reductase activity and the oxygen consumption potential in the muscle and hereby minimise the degree of blooming. The more pronounced influence of the experimental diet on the degree of blooming in LD compared to SM may be explained by the lower T(45min) in LD, which minimise denaturation of the enzymatic processes. This clearly shows that the diet composition can be used to control the extent of blooming in pork. Finally, despite the high content of grass meal in the muscle-glycogen-reducing finishing diet, this diet had negligible influence on the colour of the back fat and stripped bacon fat. PMID- 22062312 TI - Preservation of porcine blood quality by means of lactic acid bacteria. AB - The capacity of 12 lactic acid bacteria (LAB) strains to preserve porcine blood during storage was evaluated. A general ability of LAB to prevent blood's hemolysis and to maintain the functional properties of plasma was observed. Two strains, PS99 (Enterococcus raffinosus) and TA43 (Lactobacillus reuteri), were selected for studies at 5 degrees C according to their antibacterial activity in blood stored at 15 degrees C. After 144h at 5 degrees C, lower counts of coliforms, Pseudomonas spp., proteolytic and hemolytic bacteria were obtained in blood containing either PS99 or TA43 as compared to the non-inoculated blood. When inulin (2%) was added to blood, higher inhibition values were obtained and Enterococcus raffinosus (PS99) showed the best abilities for blood preservation. On the basis of these results it seems worthwhile to supplement blood with inulin and to inoculate it with an active LAB strain to avoid undesirable changes during chill storage, especially useful to prevent the effects of a cold-chain breakdown. PMID- 22062313 TI - Experimental infection by capillary tube feeding of Rhipicephalus sanguineus with Bartonella vinsonii subspecies berkhoffii. AB - It has been speculated that ticks may serve as vectors of Bartonella species. Circumstantial, clinical, epidemiological and serological evidence suggest that B. vinsonii subspecies berkhoffii (B. v. berkhoffii) might be transmitted by Rhipicephalus sanguineus. The purpose of the present study was to determine whether adult R. sanguineus ticks can be infected with a B. v. berkhoffii genotype II isolate via capillary tube feeding and whether the infection can then be transmitted from adult females to their eggs via trans-ovarial transmission. Furthermore, tick fecal material was also collected and screened as a possible source of infectious inoculum for canine infections. B. v. berkhoffii DNA was detected in 50% (7 of 14) of females that did not oviposit and in 14.3% (2 of 14) of female ticks that laid eggs, but not detected in egg clutches (100 eggs/female). DNA was also detected in tick feces collected on days 2 through 6 post-capillary tube feeding, however, dogs (n=3) did not become bacteremic or seroconvert when inoculated with tick fecal material. Therefore, trans-ovarial transmission of B. v. berkhoffii by R. sanguineus is unlikely, but further studies are needed to determine if tick fecal material can serve as a source of infection to canines. PMID- 22062314 TI - Colour evaluation of chorizo de Pamplona, a Spanish dry fermented sausage: Comparison between the CIE L(*)a(*)b(*) and the Hunter lab systems with illuminants D65 and C. AB - Objective colour evaluation was determined for 33 samples of "chorizo de Pamplona" using the CIE L(*)a(*)b(*) and the Hunter system with two illuminants (D65 and C). Highly significant differences between the measures obtained with the two illuminants were found for the three colour co-ordinates (L(*)a(*)b(*) and Lab) in both systems. The highest coefficient of variation in b was with the Hunter system and in a was with the CIE L(*)a(*)b(*) system, suggesting that the CIE system is better for separating samples according to yellowness, while the Hunter system is better for separating samples according to redness. Correlations with sensory evaluation were similar for both systems and illuminants, the lowest values being for yellowness. PMID- 22062315 TI - Causes for variation in pork quality. AB - Research was carried out on 260 pigs that were slaughtered in 12 batches in the slaughter facilities of ID-DLO at Zeist. The practical circumstances were highly standardized. The 'animals' meat quality was good with only little variation; 46 animals showed a 'slightly' aberrant quality and 6 'slight' DFD. Carcasses within the quality categories 'PSE' and 'slight' PSE did not occur. Statistically significant effects on meat quality could be shown for the duration of the resting period before slaughter and the muscular contractions occurring while stunning, shackling and exsanguination, despite the minor variation in pork quality under standardization. A longer resting period before slaughter induced significantly lower temperatures in the m.semimembranosus and the loin at 45 min post mortem and a slightly higher ultimate pH, accompanied by a somewhat darker colour (24hr post mortem). A connection between the animal's behaviour at the fattening station and ultimate pork quality could not be shown. The same counts for fighting in the resting pen of the slaughter house and the pig's behaviour in the stunning area. Muscular contractions during and after stunning had a negative effect on pork quality, causing a more rapid drop in pH, a faster development of rigor mortis and a reduced water holding capacity. An imperfect electrical stunning procedure caused an increase in muscular contractions. PMID- 22062316 TI - Effect of NaCl, polydextrose, and storage conditions on the functional characteristics and microbial quality of pre- and post-rigor salted beef. AB - The functionality and microbial storage life of pre-rigor beef mince stored at 1.5 degrees C under vacuum or a saturated carbon dioxide atmosphere, or at -18 degrees C in polyethylene bags, was investigated. Salt (2% w w ) or salt plus the cryoprotectant Polydextrose((r)) (2%/2.6% w w ) was added pre-rigor to some samples. Chilled storage decreased salt soluble protein (SSP) by 13-18% (P < 0.01); frozen storage decreased SSP content by 20%. Pre-rigor salted mince in saturated carbon dioxide packs had a satisfactory microbial quality after 12 weeks storage. The cook yield of finely comminuted sausage batters made from that mince and from fresh pre-rigor mince were similar, although batter stress and strain decreased with chilled storage. Adding Polydextrose((r)) to salted mince improved batter strain compared with the non-additive and salt-only samples and improved batter stress compared with the salt-only samples. The microbial storage life of chilled vacuumpacked unsalted mince was less than 6 weeks; pre-rigor salting increased its storage life. PMID- 22062317 TI - Sarcomere shortening and contraction nodes in stretched-restrained ovine myofibres during post mortem storage. AB - Myofibres of muscles removed from the carcass shorten during rigor mortis. Whether myofibres of stretched and restrained muscle tissues shorten during post mortem storage was examined. Muscle strips removed from the semimembranosus muscle of sheep before rigor onset were stretched and restrained. The muscle strips were fixed separately in formalin solution from 1.5 hr to 12 days post mortem, and embedded in paraffin. Sections were stained with Mallory-azan. Some myofibres in the pre-rigor-excised and stretched-restrained muscle strips had contraction nodes at 1 day post mortem. The contraction node did not increase in frequency hereafter. Two to several successive sarcomeres shortened regularly to form the nodes parallel to the Z-line. In addition, several successive sarcomeres shortened partly and successively from one side to the other side to form the nodes oblique to the Z-line. Oblique and irregular contraction nodes appear to cause kinks or bends of myofibres. Sarcomere lengths were not always uniform in individual myofibres. Formation of contraction nodes and shortening of partial sarcomeres in the stretched-restrained myofibres indicate that the myofibres shorten individually during rigor mortis and vary in shortening states as in muscles left on the carcass. PMID- 22062318 TI - Influence of sodium chloride on antioxidant enzyme activity and lipid oxidation in frozen ground pork. AB - Ground pork containing 0-2.0% NaCl was stored at -15 degrees C for 10 weeks. During storage both thiobarbituric acid reactive substances (TBARS) and lipid peroxides increased with increasing NaCl concentrations. The activity of catalase (CAT), glutathione peroxidase (GSH-Px) and Superoxide dismutase (SOD) decreased 8, 32 and 27%, respectively, after 10 weeks of storage. CAT and SOD activity decreased primarily during the first week while GSH-Px activity decreased for up to 4 weeks. To determine if NaCl influenced enzyme inactivation rates, the activity of the antioxidant enzymes from stored, salted (0.5-2.0%) ground pork were determined at equal ionic strengths. Under these conditions, NaCl was not observed to accelerate CAT, SOD and GSH-Px inactivation in ground muscle during storage. However, altering ionic strength (0.5-2.0% NaCl) in the enzymes assays decreased the activity of muscle-extracted CAT, SOD and GSH-Px suggesting that NaCl could alter the activity of these enzymes in salted pork. The ability of NaCl to reduce the activity of the antioxidant enzymes could be partially responsible for the lower oxidative stability of salted muscle foods. PMID- 22062319 TI - Breed effect on carcase and meat quality of suckling lambs. AB - The influence of breed on carcase and meat quality traits was studied in 48 suckling lambs (approximately 1 month old) from the Churra, Castellana and Manchega Spanish breeds and Awassi crosses. Carcase quality traits were determined by visual assessment and objective measurements. Meat quality was assessed by instrumental and sensory analysis. Breed effect was significant for fatness, carcase conformation and fat colour (visual indicators); dressing %, carcase weight, carcase length, buttock and chest measurements, and lean and fat proportions in the left half of the carcase. A significant breed effect was observed for some instrumental measurements of meat quality (meat colour and cooking losses), and for some sensorial attributes (tenderness and juiciness). These results suggest that there is a measurable effect of breed on both carcase and meat quality traits in this type of young suckling lamb, owing to differences in precocity and inherent productive capabilities. PMID- 22062320 TI - Bos indicus-cross feedlot cattle with excitable temperaments have tougher meat and a higher incidence of borderline dark cutters. AB - Temperament ratings based on a numerical scale (chute score) were assessed during weighing and handling of cattle at a feedlot. Breeds studied included Braford, Red Brangus and Simbrah. Cattle were fed to a constant fat thickness of 9 to 13 mm (target = 11 mm) over the 12th rib as determined by periodic ultrasound measurements. Cattle were slaughtered in a commercial slaughter plant and stunned by captive bolt. Temperament rating had a significant effect on the incidence of borderline dark cutters which were downgraded by a USDA grader (P = 0.01). Temperament score also had a significant effect on tenderness (P < 0.001) as evaluated by Warner-Bratzler Shear (WBS) force at day 14 post mortem. The calmest animals which stood still when restrained in a hydraulic squeeze chute had a mean WBS force of 2.86 +/- 11 kg and cattle which became highly agitated and struggled violently during restraint averaged 3.63 +/- 19 kg. Forty percent of these cattle had WBS force values which were over 3.9 kg which is a threshold value for acceptability in food service establishments. These data show that cattle with the most excitable temperament ratings produce carcasses with tougher meat and a higher incidence of borderline dark cutters than cattle with calm temperament ratings. PMID- 22062321 TI - Changes in proteins during the ripening of Spanish dried beef 'Cecina'. AB - Changes in the solubility of sarcoplasmic and myofibrillar proteins were tracked in Semitendinosus and Rectus femoris muscles during the ripening process of Spanish 'Cecina'. The extractability of both types of proteins decreased during the ripening. This phenomenon was more marked in the initial stages of processing. Electrophoretic studies of the myofibrillar proteins showed the virtual disappearance of the myosin heavy chain, troponin C and myosin light chain 2 from the smoking phase onward and the appearance of three components of molecular weight of about 65, 70 and 75 kda during ripening. The remaining proteins did not suffer appreciable changes. PMID- 22062322 TI - Fracture energy during slicing of frozen meat by a vibrating knife. AB - The force, and hence fracture energy, required to cut horse quadriceps muscle, using a knife which was vibrated in the direction of material feed, were measured over a range of temperatures (-1.5 to -32.5 degrees C), vibration frequencies (no vibration and 1 to 1000 Hz), accelerations (0.073 to 75 m s(-2)), thicknesses (0 to 40 MUm off-cut), and direction to the muscle grain. High vibration accelerations (75 m s(-2)) resulted in reduction of the cutting force; the reduction was independent of the off-cut thicknesses and resulted from lowering the coefficient of friction between the vibrating blade and the frozen meat. Rows of ice formed by the blade showed that pressure melting of the ice around the cutting region occurred during cutting and suggested that a hydrodynamic lubricating layer of water reduced the friction of the vibrating blade. PMID- 22062323 TI - Evaluation of cathepsin B levels in fresh thighs selected for cured raw ham production. AB - Excessive meat tenderization in cured raw Parma ham has recently been correlated with abnormal levels of cathepsin B in freshly slaughtered thigh meat. We have developed a visual assay employing the substrate Z-Arg-Arg-NNapOMe for the quantitative detection of active cathepsin B levels in pork thigh muscle homogenates. The work was based on a kinetic characterization, in steady state condition, of pig muscle cathepsin B with several peptidyl chromophoric substrate analogs. This assay can easily and safely be performed by non-specialized personnel directly in the slaughterhouse or in the factory, for an early quality evaluation of thighs selected for Parma ham production. Our characterization has further indicated that the catalytic properties of porcine muscle cathepsin B and those of isoforms from other animal and plant species are practically identical. This is particularly evident in the commercially available bovine spleen isoform, which was employed as a model enzyme in most of the experiments. PMID- 22062324 TI - Robust control of speed and temperature in a power plant gas turbine. AB - In this paper, an H(infinity) robust controller has been designed for an identified model of MONTAZER GHAEM power plant gas turbine (GE9001E). In design phase, a linear model (ARX model) which is obtained using real data has been applied. Since the turbine has been used in a combined cycle power plant, its speed and also the exhaust gas temperature should be adjusted simultaneously by controlling fuel signals and compressor inlet guide vane (IGV) position. Considering the limitations on the system inputs, the aim of the control is to maintain the turbine speed and the exhaust gas temperature within desired interval under uncertainties and load demand disturbances. Simulation results of applying the proposed robust controller on the nonlinear model of the system (NARX model), fairly fulfilled the predefined aims. Simulations also show the improvement in the performance compared to MPC and PID controllers for the same conditions. PMID- 22062325 TI - Partial stabilization of uncertain nonlinear systems. AB - In this paper, the problem of robust partial stabilization is considered and two approaches for partial stabilization of uncertain nonlinear systems are presented. In these approaches, the nonlinear dynamical system is divided into two subsystems, which are called the first and the second subsystems. This division is done based on the required stability properties of the system's states. The reduced input vector (the vector that includes components of the input vector appearing in the first subsystem) is designed to asymptotically stabilize the first subsystem. In the first approach, a new partial stabilization technique, based on the first order sliding mode control idea is proposed. In the proposed method, hereafter called the partial sliding mode, a sliding surface is designed such that restricting the motion on this surface guarantees the stability of only the first part of the system's state. In the second approach, a Lyapunov-based controller is proposed for partial stabilization and then an additional feedback control is designed so that the overall feedback law guarantees a robust manner in the presence of uncertainties. PMID- 22062326 TI - Treatment of classic porokeratosis of Mibelli with Q-switched ruby laser. PMID- 22062327 TI - Finding meaning in meaningful use: understanding the health information technology for economic and clinical health act and its impact on nursing practice. PMID- 22062328 TI - Leading change: a patient services division's journey through the computerization and reorganization of their policies, procedures, and guidelines. PMID- 22062329 TI - Safety and mobility of vulnerable road users: pedestrians, bicyclists, and motorcyclists. AB - Traffic safety has improved greatly over the past few decades, but the progress in the safe mobility of vulnerable road users (VRUs) - especially motorcycle riders - has not been as consistent. The changing trends towards healthier and eco-friendlier lifestyle, coupled with the rising costs of fuel have increased the exposure and injury risk of pedestrians, motorcyclists, and bicyclists, especially in urban areas. To address the safe mobility issues of VRUs, Israel's National Road Safety Authority organized an international conference on the topic. This special issue contains the papers of the three plenary talks related to the safe mobility of each of the VRUs, and 18 more papers of the over 100 papers presented at the conference that were accepted for publication in AAP following the Journal's review process. PMID- 22062330 TI - Pedestrian crash trends and potential countermeasures from around the world. AB - As automobile transportation continues to increase around the world, bicyclists, pedestrians, and motorcyclists, also known as vulnerable road users (VRUs), will become more susceptible to traffic crashes, especially in countries where traffic laws are poorly enforced. Many countries, however, are employing innovative strategies to ensure that road users can more safely navigate the urban landscape. While bicyclists and motorcyclists are important road users, this paper will focus on pedestrian crash problems and solutions. Pedestrians are most at risk in urban areas due in part to the large amount of pedestrian and vehicle activity in urban areas. With this in mind, designing safe, accessible, and comprehensive facilities for pedestrians is vital to reducing pedestrian crashes. This paper will provide some insight into the magnitude of the pedestrian crash problem around the world, and will offer some lessons learned from several countries, particularly in Europe and the U.S., for improving pedestrian safety. Beginning with pedestrian safety statistics at the global, regional, and national levels, this paper will address potential countermeasures and strategies for improving pedestrian safety from an international perspective. PMID- 22062331 TI - Powered two wheelers in a changing world-challenges and opportunities. AB - Powered two wheelers (PTWs) come in diverse forms and are used for a range of purposes in very different parts of the world. In many parts of the world, the forms and uses of PTWs are changing, influenced by social, economic and demographic changes. Most of the challenges associated with PTWs relate to safety, while the majority of the opportunities relate to mobility. The challenges for improving safety relate to the PTW user, other road users, the road environment, the vehicle, data and research, and socio-political dimensions. The relative importance of particular challenges varies between developed and developing countries, and among developing countries according to whether PTWs are largely used for recreation or for transport. PTWs present a range of psychological, transport, economic and environmental opportunities to individuals and societies. The fun and excitement of riding PTWs is a major motivator for their purchase and use for recreational purposes, both off-road and on-road. The transport and economic advantages to the individual also need to be considered. At a societal level, research has examined the potential for increasing PTW volumes to reduce fossil fuel use and traffic congestion in busy cities. The future of PTWs may differ greatly between countries and environmental and technological changes are leading to an evolution in the form of PTWs to encompass new modes of personal transportation. PMID- 22062332 TI - How to make more cycling good for road safety? AB - This paper discusses the current level of the road safety problems of cycling and cyclists, why cyclists run relatively high risks, and why cyclists may be considered as 'vulnerable road users'. This paper is based on peer-reviewed research which give some idea how to reduce the number of cyclist casualties. However, this research is rather limited and the results cannot (easily) be transferred from one setting or country to another: generalization of results should only be done with the utmost care, if it is to be done at all. Interventions to reduce cyclist casualties worldwide seem to be of an incidental nature; that is to say, they are implemented in a rather isolated way. In a Safe System approach, such as the Dutch Sustainable Safety vision, the inherent risks of traffic are dealt with in a systematic, proactive way. We illustrate how this approach is especially effective for vulnerable road users, such as cyclists. Finally, the paper addresses the question of whether it is possible to make more cycling good for road safety. We conclude that when the number of cyclists increases, the number of fatalities may increase, but will not necessarily do so, and the outcome is dependent on specific conditions. There is strong evidence that well-designed bicycle facilities-physically separated networks-reduce risks for cyclists, and therefore have an impact on the net safety result, for example if car-kilometres are substituted by bicycle kilometres. Policies to support cycling should incorporate these findings in order to make more cycling good for road safety. PMID- 22062333 TI - Pedestrians' behaviour in cross walks: the effects of fear of falling and age. AB - Pedestrians are exposed to risks when crossing roads in urban areas. The crossing behaviour of pedestrians was studied as a factor contributing to their exposure to risks on the road and to their involvement in road accidents. This work explores two specific aspects of crossing behaviour: crossing speed and head pitches-the proportion of time pedestrians point their heads down (rather than towards the traffic) when crossing a road. The last one is used as an indicator of the (lack of) attention to cross-traffic. We also explored the possible effect of fear of falling (FOF) among pedestrians, as it might be associated with slow walking, less attention to cross traffic, and more attention to the pavement and their footsteps. This paper reports on a field study that combined an observatory technique with short survey. 203 pedestrians in two sites (signalised and unsignalised crosswalks) were video recorded while crossing the road. The FOF of pedestrians and other measures of pedestrian behaviour at crosswalks were revealed by means of questionnaire. Age and gender had the most significant effects on crossing speed, and FOF had a significant effect on the proportion of downward head pitches during crossing. PMID- 22062334 TI - Advance yield markings and drivers' performance in response to multiple-threat scenarios at mid-block crosswalks. AB - This study compares, on a simulator, drivers' performance (eye fixations and yielding behavior) at marked mid-block crosswalks in multi-threat scenarios when the crosswalks have advance yield markings and pedestrian crosswalk prompt signs versus their performance in such scenarios when the crosswalks have standard markings. Advance yield markings and prompt signs in multi-threat scenarios lead to changes in drivers' behaviors which are likely to reduce pedestrian-vehicle conflicts, including increases in the likelihood that the driver glances towards the pedestrian, increases in the distance at which the first glance towards the pedestrian is taken, and increases the likelihood of yielding to the pedestrian. PMID- 22062335 TI - Age-related differences in street-crossing safety before and after training of older pedestrians. AB - International accident statistics indicate that elderly pedestrians make up an extremely vulnerable road-user group. Past research has shown that older adults make many unsafe street-crossing decisions and adopt insufficient safety margins, especially when vehicles are approaching at high speed. Apart from studies on road design and speed-limit countermeasures, there is surprisingly no road-safety research on behavior-based measures to improve older pedestrians' safety. In this line, the present study was aimed at (i) assessing the effectiveness of a training program for older pedestrians that combined behavioral and educational interventions, and (ii) examining whether and to what extent age-related differences in street-crossing safety could be reduced after training older adults. Twenty seniors were enrolled in a training program. Before, immediately after, and six months after training, street-crossing behavior was assessed using a simulated street-crossing task. Twenty younger participants performed the same simulated task to obtain a baseline measure. The results showed that the training produced significant short- and long-term benefits, due to a shifting of the decision criteria among the older participants towards more conservative judgments. When compared with the younger group, the older participants improved their behavior considerably so that significant differences in the mean safety related indicators were no longer observed. However, the older participants' ability to take the oncoming car's speed into account did not improve. Even after training, and contrary to younger adults, older participants were found to make more and more unsafe decisions as the car's speed increased, putting them at a higher risk at high speeds. This finding may reflect age-related perceptual and cognitive difficulties that cannot be remedied by a behavioral or educational training method. The present findings underline that high speed is an important risk factor for elderly pedestrians that should be handled by effective speed reduction measures (i.e. speed ramps, road narrowing). PMID- 22062336 TI - The perception of pedestrians from the perspective of elderly experienced and experienced drivers. AB - We examined hazard perception (HP) abilities among elderly experienced and experienced drivers, with regard to the presence of pedestrians in residential areas. Two evaluation methods were used: (a) observation of traffic scene videos and pressing a button when a hazardous situation was identified, and (b) driving in a driving simulator. The results of the video observation method showed that elderly drivers had a longer response time for hazard detection. In addition, four of the eight pedestrian-related events were difficult for elderly drivers to perceive when compared to experienced drivers. Elderly drivers, shown to have limited useful field of view, may also be limited in their ability to detect hazards, particularly when located away from the center of the screen. Results from the simulator drive showed that elderly drivers drove about 20% slower than experienced drivers, possibly being aware of their deficiencies in detecting hazards and slower responses. Authorities should be aware of these limitations and increase elderly drivers' awareness to pedestrians by posting traffic signs or dedicated lane marks that inform them of potential upcoming hazards. PMID- 22062337 TI - Mapping patterns of pedestrian fatal accidents in Israel. AB - This study intends to provide insight into pedestrian accidents by uncovering their patterns in order to design preventive measures and to allocate resources for identified problems. Kohonen neural networks are applied to a database of pedestrian fatal accidents occurred during the four-year period between 2003 and 2006. Results show the existence of five pedestrian accident patterns: (i) elderly pedestrians crossing on crosswalks mostly far from intersections in metropolitan areas; (ii) pedestrians crossing suddenly or from hidden places and colliding with two-wheel vehicles on urban road sections; (iii) male pedestrians crossing at night and being hit by four-wheel vehicles on rural road sections; (iv) young male pedestrians crossing at night wide road sections in both urban and rural areas; (v) children and teenagers crossing road sections in small rural communities. From the perspective of preventive measures, results suggest the necessity of designing education and information campaigns for road users as well as allocating resources for infrastructural interventions and law enforcement in order to address the identified major problems. PMID- 22062338 TI - Characterization of pedestrian accidents and an examination of infrastructure measures to improve pedestrian safety in Israel. AB - The high share of pedestrian fatalities in Israel provided the impetus for this study which looked for infrastructure solutions to improve pedestrian safety. First, a detailed analysis of pedestrian accidents in 2006-2007, with an emphasis on the infrastructure characteristics involved, was performed; it found that 75% of the fatalities and 95% of the injuries occurred in urban areas, the majority of cases occurring on road sections (not at junctions). About 80% of the accidents took place when a pedestrian crossed the road, the majority of them at non-crosswalk locations or at non-signalized crosswalks. International comparisons showed that the characteristics of fatal pedestrian accidents in Israel were similar to the average pedestrian accident in Europe in terms of accident location, time, and the demographic characteristics of the victims. A typology of pedestrian fatalities in Israel was built for the years 2003-2006; it demonstrated a high share of accidents at these locations: in Jewish or mixed population towns-not at pedestrian crossings on urban street sections, and both at pedestrian crossings and not at pedestrian crossings at urban junctions; in Arab towns; and on dual-carriageway rural roads. Second, based on a literature study, a summary of about 60 pedestrian-safety-related measures was developed. Third, to diagnose the infrastructure characteristics and deficiencies associated with pedestrian accidents, detailed field studies were carried out at 95 urban locations. A major finding revealed that more than 80% of the sites with a high concentration of pedestrian-vehicle accidents in Israel were situated on arterial multi-lane streets belonging to city centers, where on a micro-level there were no indications of major deficiencies in the basic design elements of most sites. Finally, cross-checking of the safety problems identified and the infrastructure solutions available provided lists of measures recommended for application at various types of sites. It was concluded that in order to generate a significant change in the state of pedestrian injury in Israel, a move from spot treatment to a systemic treatment of the problem is required. A systemic inquiry and the transformation of the urban road network should be performed in order to diminish the areas of vehicle-pedestrian conflicts and to significantly reduce vehicle speeds in areas of pedestrian presence and activity. PMID- 22062339 TI - Perspectives for motorcycle stability control systems. AB - On a global scale, motorcyclists are typically over-represented in crash statistics. This trend is increasing as although total road crashes and fatalities have decreased over the last fifteen years, motorcycle crash volumes have not. This paper describes the potential of stability control systems to help save motorcyclists' lives. It summarizes safety research conducted and commissioned by the Federal Highway Research Institute (Bundesanstalt fur Strabetaenwesen, BASt) during the last twenty-five years, with particular focus on the authors' own work in the last five years, and the state of the art in motorcycle control systems. The conclusion is that further investigation and improvement of these systems should be encouraged. Unfortunately, active stabilization of motorcycles is not presently possible and may not be possible in the future. Therefore, further development, evolution and optimization of Anti Lock Brake Systems (ABSs) and Traction Control Systems (TCS) should be undertaken, and Anti-Lock Brake Systems (ABSs) should be mandatory on powered two wheelers. These steps will make the powered two-wheeler a safer urban transportation system. PMID- 22062340 TI - Recognisability of different configurations of front lights on motorcycles. AB - One often discussed reason for motorcyclists' high risk of accidents is that they are less conspicuous to other road users than are other motorised vehicles. The present paper aims to identify a front signal pattern created by additional light sources that would make motorcycles clearly and quickly distinguishable from other vehicles, and that would therefore facilitate localisation and identification of motorcycles. Results of a laboratory experiment have shown that motorcycles with a T-shaped light configuration are more quickly identified, particularly when the motorcycles are in visual competition with other motorised road users. Furthermore, analysis of gaze behavior showed that they were faster fixated by the subjects in the experiment, and the mean duration of fixations was shorter. The practical implications of this experiment and the need for further research are discussed. PMID- 22062341 TI - Why do car drivers fail to give way to motorcycles at t-junctions? AB - Studies of accident statistics suggest that motorcyclists are particularly vulnerable to collisions with other vehicles which pull out of side roads onto a main carriageway, failing to give way to the approaching motorcycle. Why might this happen? The typical response of the car driver is that they looked in the appropriate direction but simply failed to see the motorcycle. To assess the visual skills of drivers in such scenarios we compared the behaviour of novice and experienced drivers to a group of dual drivers (with both car and motorcycle experience). Participants watched a series of video clips, displayed across three screens, depicting the approach to various t-junctions. On reaching the junction, participants had to decide when it was safe to pull out. Responses and eye movements were measured. The results confirmed that dual drivers had the safest responses at junctions, especially in the presence of conflicting motorcycles. On a range of visual measures both novice and experienced drivers appeared inferior to dual drivers, though for potentially different reasons. There were however no differences in the time it took all drivers to first fixate approaching motorcycles. Instead the differences appeared to be due to the amount of time spent looking at the approaching motorcycle. The experienced drivers had shorter gazes on motorcycles than cars, suggesting that they either process less salient motorcycles faster than cars, or that they terminated the gaze prematurely perhaps because they did not realise they were fixating a motorcycle. We argue that this is potential evidence for an oculomotor basis for Look But Fail To See errors. PMID- 22062342 TI - Attention and search conspicuity of motorcycles as a function of their visual context. AB - BACKGROUND: Over the years, PTWs' number of accidents have increased dramatically and have accounted for a high percentage of the total traffic fatalities. The majority of those accidents occur in daylight, clear weather, and at light to moderate traffic conditions. The current study included two experiments. The first experiment evaluated the influence of PTW attention conspicuity on the ability of un-alerted viewers to detect it, whereas the second experiment evaluated the PTWs search conspicuity to alerted viewers. The independent variables in both experiments included driving scenarios (urban and inter-urban), PTW rider's outfit (black, white, and reflective) and PTW distance from the viewer. METHOD: 66 students participated in experiment 1. Every participant was presented with a series of pictures and was asked to report all the vehicle types present in each picture. Experiment 2 included 64 participants and incorporated the same pictures as experiment 1. However, in this experiment the participants were instructed to search the pictures for a PTW and to report its presence or absence as soon as they reach a decision. RESULTS: In experiment 1 the detection of a PTW depended on the interaction between its distance from the viewer, the driving scenario and PTW rider's outfit. For an un-alerted viewer when the PTW was distant the different outfit conditions affected its' attention conspicuity. In urban roads, where the background surrounding the PTW was more complex and multi-colored, the reflective and white outfits increased its attention conspicuity compared to the black outfit condition. In contrast, in inter-urban roads, where the background was solely a bright sky, the black outfit provided an advantage for the PTW detectability. In experiment 2, the average PTW detection rate of the alerted viewers was very high and the average reaction time to identify the presence of a PTW was the shortest in the inter-urban environment. Similar to the results of experiment 1, in urban environments the reflective and white clothing provided an advantage to the detection of the PTW, while in the inter-urban environment the black outfit presented an advantage. Comparing the results of the two experiments revealed that at the farthest distance, the increased awareness in the search conspicuity detection rates were three times higher than in the attention conspicuity. CONCLUSIONS: The conspicuity of a PTW can be increased by using an appropriate rider's outfit that distinguishes him/her from the background scenery. Thus, PTW riders can actively increase their conspicuity by taking into account the driving route (crowded urban/inter urban), eventually increasing the probability of being detected by the other road users. In addition, increasing the alertness and expectancy of drivers to the presence of PTWs can increase their search conspicuity. PMID- 22062343 TI - Attending overtaking cars and motorcycles through the mirrors before changing lanes. AB - Right of way violation crashes are the most common type of accidents that motorcyclists face. This study assessed right of way decisions in scenarios which require noticing whether there is traffic from behind that is about to overtake. A test was created which presents participants clips with a wide field of vision (from a driver's perspective in a moving vehicle), with mirror information inset that allows either cars or motorcycles that are about to overtake, to be attended. Novice and experienced car drivers, and dual drivers (with both car and motorcycle experience), watched these clips while their eye movements were monitored. The results indicated that in the rear-view and the right-side mirrors, and in the right hand lane, conflicting motorcycles garnered more attention than conflicting cars. This pattern however was particularly driven by the dual drivers group. Additionally, novice drivers and dual drivers made more use of the right side mirror than the experienced drivers. Dual drivers also made more use of the rear view mirror than experienced drivers. Finally, significant positive correlations that were found between percentages of safe manoeuvres and measures of visual search provide direct evidence demonstrating that the frequency of risky manoeuvres was indeed larger in those cases where less time was spent gazing at the mirrors, indicating that the additional attention devoted to process conflicting vehicles contributes to reduce risky manoeuvres. The general pattern of results also provides some indirect support that non motorcyclists drivers are more likely to have Look But Fail To See errors with conflicting motorcycles than motorcyclist drivers. PMID- 22062344 TI - Motorcycle riders' perception of helmet use: complaints and dissatisfaction. AB - In accidents which involve two-wheeled vehicles the helmet plays a life-saving role, but very little is known about the motorcycle rider's perception of the helmet. We evaluated the relationships between having been involved in an accident and dissatisfaction with the helmet, and between the perception of motorcycle riders and the objective features of the helmet. This was a case control study: riders of motorized two-wheelers who had been involved in accidents (accident cases) were compared against a similarly interviewed sample of riders that had not been in accidents (control cases). Information about the driver, the vehicle and the helmet was collected in all interviews. To evaluate the relationships, logistic regressions were carried out. The majority of drivers were dissatisfied with their helmets, but no evidence was found to link this dissatisfaction with having been involved in an accident. The two most common complaints related to noisiness, followed by the helmet visor. Complaints did not seem to be statistically associated with physical features of the helmet. PMID- 22062345 TI - Comparison of two warning concepts of an intelligent Curve Warning system for motorcyclists in a simulator study. AB - Curve crashes are a particular matter of concern regarding motorcycle riding safety. For this reason, an intelligent Curve Warning system has been designed that gives the riders support when negotiating a curve. The system has been tested in a simulator study carried out with 20 test riders. The subjects performed three rides: one without the system (baseline) and two experimental rides using a version of the Curve Warning system, one providing the warnings by a force feedback throttle and one by a haptic glove. The effects of the two system versions were evaluated both in terms of the simulated riding performance and the subjective assessment by the riders. A descriptive analysis of the riders' reactions to the warnings shows that the warnings provided by both system versions provoke an earlier and stronger adaptation of the motorcycle dynamics to the curve than when the riders do not use the system. Riding with the Curve Warning system with the haptic glove furthermore leads to a reduction of critical curve events. The riders' subjective workload level was not affected by the system use, whereas the Curve Warning system with the force feedback throttle required an increased attention. The comparison of the riders' opinions about the system reveals a preference of the Curve Warning system with the haptic glove. The better acceptance of this system version suggests a higher potential in the enhancement of riding safety. PMID- 22062346 TI - Evaluation of bike boxes at signalized intersections. AB - This paper presents a before-after study of bike boxes at 10 signalized intersections in Portland, Oregon. The bike boxes, also known as advanced stop lines or advanced stop boxes, were installed to increase visibility of cyclists and reduce conflicts between motor vehicles and cyclists, particularly in potential "right-hook" situations. Before and after video were analyzed for seven intersections with green bike boxes, three intersections with uncolored bike boxes, and two control intersections. User perceptions were measured through surveys of cyclists passing through five of the bike box intersections and of motorists working downtown, where the boxes were concentrated. Both the observations and survey of motorists found a high rate of compliance and understanding of the markings. Overall, 73% of the stopping motor vehicles did not encroach at all into the bike box. Both motor vehicle and bicycle encroachment in the pedestrian crosswalk fell significantly at the bike box locations compared to the control intersections. The bike boxes had mixed effects on the motorists' encroachment in the bicycle lane. The number of observed conflicts at the bike box locations decreased, while the total number of cyclists and motor vehicles turning right increased. Negative-binomial models based upon the data predict fewer conflicts with the boxes, particularly as right-turning motor vehicle volumes increase. Observations of yielding behavior at two bike box and one control intersection found an improvement in motorists yielding to cyclists at the bike box locations. Differences in the traffic volumes and location contexts make firm conclusions about the effects of green coloring of the boxes difficult. Higher shares of surveyed motorists felt that the bike boxes made driving safer rather than more dangerous, even when the sample was narrowed to respondents who were not also cyclists. Over three-quarters of the surveyed cyclists thought that the boxes made the intersection safer. PMID- 22062347 TI - Bicycle injuries: a matter of mechanism and age. AB - Bicycle riding is a popular form of recreation with positive health and environmental effects. These road users are vulnerable to serious injuries, especially when motor vehicles are involved. The goal of this study was to characterize cyclist-related injuries according to motor vehicle involvement for adults versus children. A retrospective study was carried out using data from 11 trauma centers in the Israeli National Trauma Registry (2001-2007). Injuries were classified according to whether a motor vehicle was involved, and differences in injury characteristics were assessed for adults (18+ years) versus children (1-17 years). A total of 5529 patients were hospitalized for bicycle injuries, of whom 1765 were adults and 3764 were children. Thirty percent (n=1662) of all bicycle injuries involved motor vehicles, although the rate of injuries resulting in hospitalization was 37% among adults and 27% among children. Injury characteristics and hospital resource utilization differed substantially by age group. Cyclists struck by a motor vehicle presented with more severe injuries requiring more hospital resources and resulting in poorer outcomes than those not involved with motor vehicles. The interaction effect between motor vehicle involvement and age was significant for torso injuries and need for medical imaging. We found that injury characteristics, hospital resource utilization and health-related outcomes for bicycle injuries are highly dependent on patient's age and mechanism of injury. Effect modification of motor vehicle involvement by age may in part reflect physicians' attitudes toward pediatric imaging. The risks identified in this study should be used for preparedness and management of trauma hospitalizations from bicycle injuries. PMID- 22062348 TI - Sustainable road safety: a new (?) neighbourhood road pattern that saves VRU lives. AB - Both the UN (2007) and World Health Organizations (2004) have declared the enormous social and economic burden imposed on society by injuries due to road collisions as a major global problem. While the road safety problem is not new, this prominent global declaration sends an important signal of frustration regarding progress to date on reducing road collisions. It is clear that governments, communities, businesses and the public must discover ways of reducing this burden, especially as it relates to vulnerable road users (VRUs), typically meaning pedestrian and bicyclist road users. Recent comparisons of global VRU collisions statistics suggest that, in addition to mixed land use density, the layout of neighbourhood roads plays a vital role in the encouragement of walkable, safe and quiet, yet accessible and sustainable communities. The purpose of this paper was to: The Dutch Sustainable Road Safety (SRS) Program has produced a number of innovative land use and transportation initiatives for vehicular road users as well as non-vehicular VRUs. Following from the Dutch initiatives, these new 3-way offset, and fused grid neighbourhood patterns appear to not only have positive effects in encouraging mode split (i.e. increasing walking and bicycling, and transit), slowing traffic, and reducing energy consumption and GHG emissions; but also, to hold potential to improve road safety. To test the road safety hypothesis, UBCO researchers evaluated the level of road safety relative to five neighbourhood patterns - grid, culs-de-sac, and Dutch Sustainable Road Safety (SRS) (or limited access), 3-way offset, and fused grid networks. Analysis using standard transportation planning methodology revealed that they would maintain both mobility and accessibility. Analysis using standard road safety analysis methodology further revealed that these 3-way offset, and fused grid patterns would significantly improve road safety levels by as much as 60% compared to prevalent patterns (i.e. grid and culs-de-sac). It is important to note that these results ignore the road safety effects of providing convenient off-road trails along trip desire lines to shift mode choice from auto to non-auto VRU modes. Subject to further research, it is intuitive that shifting trips from auto to pedestrian/bike modes will lead to reduced auto collisions. Hence, these initial results should be considered as conservative estimates, subject to further research. In before and after studies to date, researchers have shown that increasing bicycle use does not lead to a commensurate increase in bicycle collisions, but no predictive relationship has been found in the literature. Therefore, the next steps in this research are to develop collision prediction models that provide insight on VRU mode split and overall road safety. PMID- 22062349 TI - Injury protection and accident causation parameters for vulnerable road users based on German In-Depth Accident Study GIDAS. AB - Within a study of accident data from GIDAS (German In-Depth Accident Study), vulnerable road users are investigated regarding injury risk in traffic accidents. GIDAS is the largest in-depth accident study in Germany. Due to a well defined sampling plan, representativeness with respect to the federal statistics is also guaranteed. A hierarchical system ACASS (Accident Causation Analysis with Seven Steps) was developed in GIDAS, describing the human causation factors in a chronological sequence. The accordingly classified causation factors - derived from the systematic of the analysis of human accident causes ("7 steps") - can be used to describe the influence of accident causes on the injury outcome. The bases of the study are accident documentations over ten years from 1999 to 2008 with 8204 vulnerable road users (VRU), of which 3 different groups were selected as pedestrians n=2041, motorcyclists n=2199 and bicyclists n=3964, and analyzed on collisions with cars and trucks as well as vulnerable road users alone. The paper will give a description of the injury pattern and injury mechanisms of accidents. The injury frequencies and severities are pointed out considering different types of VRU and protective measures of helmet and clothes of the human body. The impact points are demonstrated on the car, following to conclusion of protective measures on the vehicle. Existing standards of protection devices as well as interdisciplinary research, including accident and injury statistics, are described. With this paper, a summarization of the existing possibilities on protective measures for pedestrians, bicyclists and motorcyclists is given and discussed by comparison of all three groups of vulnerable road users. Also the relevance of special impact situations and accident causes mainly responsible for severe injuries are pointed out, given the new orientation of research for the avoidance and reduction of accident patterns. PMID- 22062350 TI - Optimism about safety and group-serving interpretations of safety among pedestrians and cyclists in relation to road use in general and under low light conditions. AB - Drivers are known to be optimistic about their risk of crash involvement, believing that they are less likely to be involved in a crash than other drivers. However, little comparative research has been conducted among other road users. In addition, optimism about crash risk is conceptualised as applying only to an individual's assessment of his or her personal risk of crash involvement. The possibility that the self-serving nature of optimism about safety might be generalised to the group-level as a cyclist or a pedestrian, i.e., becoming group serving rather than self-serving, has been overlooked in relation to road safety. This study analysed a subset of data collected as part of a larger research project on the visibility of pedestrians, cyclists and road workers, focusing on a set of questionnaire items administered to 406 pedestrians, 838 cyclists and 622 drivers. The items related to safety in various scenarios involving drivers, pedestrians and cyclists, allowing predictions to be derived about group differences in agreement with items based on the assumption that the results would exhibit group-serving bias. Analysis of the responses indicated that specific hypotheses about group-serving interpretations of safety and responsibility were supported in 22 of the 26 comparisons. When the nine comparisons relevant to low lighting conditions were considered separately, seven were found to be supported. The findings of the research have implications for public education and for the likely acceptance of messages which are inconsistent with current assumptions and expectations of pedestrians and cyclists. They also suggest that research into group-serving interpretations of safety, even for temporary roles rather than enduring groups, could be fruitful. Further, there is an implication that gains in safety can be made by better educating road users about the limitations of their visibility and the ramifications of this for their own road safety, particularly in low light. PMID- 22062351 TI - Drivers' perception of vulnerable road users: a hazard perception approach. AB - The present study examined how experienced and young-inexperienced drivers (either trained in hazard perception or not) respond to and identify pedestrians when they appear in residential roads within populated neighborhoods and in urban roads located outside neighborhoods and usually less populated. As part of a hazard perception test, participants were connected to an eye tracking system and were asked to observe 58 traffic scene movies and press a response button each time they detected a hazardous situation. Analyzing all pedestrian-related events revealed that, regardless of driving experience or training, drivers detect pedestrians less often when they appear in urban areas and more often when they appear in residential areas. Moreover, experienced drivers processed information more efficiently than young-inexperienced drivers (both trained and untrained) when pedestrians were identified. Visual search patterns in urban and residential traffic environments are discussed. PMID- 22062353 TI - Influence of influenza A infection on capsaicin-induced responses in murine airways. AB - The principal aim of the study was to determine the influence of influenza A virus infection on capsaicin-induced relaxation responses in mouse isolated tracheal segments and clarify the underlying mechanisms. Anesthetized mice were intranasally inoculated with influenza A/PR-8/34 virus (VIRUS) or vehicle (SHAM), and 4 days later tracheal segments were harvested for isometric tension recording and biochemical and histologic analyses. Capsaicin induced dose-dependent relaxation responses in carbachol-contracted SHAM trachea (e.g., 10 MUM capsaicin produced 66 +/- 4% relaxation; n = 11), which were significantly inhibited by capsazepine [transient receptor potential vanilloid type 1 (TRPV1) antagonist], (2S,3S)-3-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-2-phenylpiperidine hydrochloride (L-733,060) [neurokinin 1 (NK1) receptor antagonist], indomethacin [cyclooxygenase (COX) inhibitor], and the combination of 6-isopropoxy-9 oxoxanthene-2-carboxylic acid (AH6809) and 7-[5alpha-([1S,1alpha(Z)-biphenyl]-4 ylmethoxy)-2beta-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid, calcium salt, hydrate (AH23848) [E-prostanoid (EP)2 and EP4 receptor antagonists, respectively], indicating that capsaicin-induced relaxation involved the TRPV1 mediated release of substance P (SP), activation of epithelial NK1 receptors, and production of COX products capable of activating relaxant EP2/EP4 receptors. Consistent with this postulate, capsaicin-induced relaxation was associated with the significant release of SP and prostaglandin E2 (PGE2) from mouse tracheal segments. As expected, influenza A virus infection was associated with widespread disruption of the tracheal epithelium. Tracheal segments from VIRUS mice responded weakly to capsaicin (7 +/- 3% relaxation) and were 25-fold less responsive to SP than tracheas from SHAM mice. In contrast, relaxation responses to exogenous PGE2 and the beta-adrenoceptor agonist isoprenaline were not inhibited in VIRUS trachea. Virus infection was associated with impaired capsaicin-induced release of PGE2, but the release of SP was not affected. In summary, influenza A virus infection profoundly inhibits capsaicin- and SP induced relaxation responses, most likely by inhibiting the production of PGE2. PMID- 22062352 TI - Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice. AB - Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading MU-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not. PMID- 22062354 TI - Chemical constituents of Stereospermum acuminatissimum and their urease and alpha chymotrypsin inhibitions. AB - Phytochemical investigation of the stem bark of Stereospermum acuminatissimum K. Schum. resulted in the isolation of 21 compounds, including two new guanine derivatives, 1,3,7-trimethylguanin-1/3-ium (1) and 3,7-dimethylguanin-1/3-ium (2), and one new phenolic long chain ester, 2-(4-hydroxyphenyl)ethyl hentriacontanoate (3). The known compounds were identified as sterequinones A, F, and H (4, 5, and 6), zenkequinones A-B (7-8), p-coumaric acid (9), methyl caffeate (10), caffeic acid (11), psilalic acid (12), syringaldehyde (13), norviburtinal (14), specioside (15), verminoside (16), tyrosol (17), eutigoside A (18), ellagic acid (19), atranorin (20), and ursolic acid (21). The metabolites were screened for their potential against urease and alpha-chymotrypsin enzymes, as urease is targeted in peptic ulcer while alpha-chymotrypsin is used to remove protein debris in ulcer. Compound 20 was found to be excellent urease inhibitor with IC(50) value of 18.2 +/- 0.03 MUM. Compounds 13 and 18-20 are reported for the first time from the genus Stereospermum. The chemotaxonomic significance of the isolated compounds was also described. PMID- 22062355 TI - Zonal differences in meniscus matrix turnover and cytokine response. AB - OBJECTIVE: To determine the mechanisms of meniscal degeneration and whether this varied zonally and from articular cartilage. DESIGN: Normal ovine menisci were dissected into inner and outer zones and along with cartilage cultured +/-IL 1alpha and TNFalpha. Glycosaminoglycan (GAG) and collagen release, and gene expression were quantified. Aggrecan proteolysis was analysed by Western blotting with neoepitope-specific antibodies. Matrix metalloproteinase (MMP)2, MMP9 and MMP13 activity was evaluated by gelatin zymography or fluorogenic assay. RESULTS: Inner meniscus was more cartilaginous containing more GAG and expressing more ACAN and COL2A1 than outer zones. Higher expression of VCAN and ADAMTS4 in medial outer and both zones of the lateral meniscus reflected their embryologic origin from cells outside the cartilage anlagen. All meniscal regions released a greater % GAG in response to cytokines; only outer zones had cytokine-stimulated collagenolysis. Cytokine-induced aggrecanolysis was primarily due to increased ADAMTS cleavage in cartilage and inner menisci but MMPs in the outer menisci. Outer menisci always released more active MMP2 than other tissues and more active MMP13 in basal and TNF-stimulated cultures. Expression of ACAN, COL1A1 and COL2A1 was decreased by both cytokines in all tissues, while VCAN was increased by IL 1alpha in cartilage and inner menisci. Metalloproteinase expression was differentially regulated by IL-1alpha and TNFalpha: ADAMTS4, MMP1, MMP3 were upregulated more by IL-1alpha in inner zones whereas ADAMTS5, MMP13 and MMP9 were more upregulated by TNFalpha in outer zones. CONCLUSIONS: Meniscal degeneration mechanisms are zonally-dependent, and may contribute to the enzymatic burden in the joint. PMID- 22062356 TI - Smoking increases the risk for colorectal adenomas in patients with Lynch syndrome. AB - BACKGROUND & AIMS: Individuals with Lynch syndrome have a high risk of developing colorectal carcinomas and adenomas at a young age, due to inherited mutations in mismatch repair genes. We investigated whether modifiable lifestyle factors, such as smoking and alcohol intake, increase this risk. METHODS: Using data from the GeoLynch cohort study, a prospective analysis of 386 subjects with Lynch syndrome, we calculated hazard ratios for the association between smoking and alcohol intake and development of colorectal adenoma. We used robust variance estimates in the calculation of 95% confidence intervals to account for dependency within families and adjusted for confounding by age, sex, smoking (in the analyses of alcohol intake), number of colonoscopies during the follow-up, colonic resection, and body mass index. RESULTS: During a median follow-up of 10 months, 58 subjects developed a histologically confirmed colorectal adenoma. The hazard ratio for current smokers was 6.13 (95% confidence interval, 2.84-13.22) and for former smokers was 3.03 (95% confidence interval, 1.49-6.16) compared with never smokers. Among ever smokers, a higher number of pack-years was associated with an increased risk for colorectal adenoma (P for trend = .03). There was a trend of alcohol intake increasing the risk of colorectal adenomas, although this was not statistically significant; the hazard ratio for the highest tertile of intake (median, 22 g/day) vs the lowest tertile (median, 0.4 g/day) was 1.56 (95% confidence interval, 0.71-3.43). CONCLUSIONS: Among people with Lynch syndrome, current smokers have an increased risk of colorectal adenomas. Former smokers have a lower risk than current smokers, but greater risk than never smokers. Individuals with Lynch syndrome should be encouraged to avoid smoking. PMID- 22062357 TI - Next-generation stool DNA test accurately detects colorectal cancer and large adenomas. AB - BACKGROUND & AIMS: Technical advances have led to stool DNA (sDNA) tests that might accurately detect neoplasms on both sides of the colorectum. We assessed colorectal neoplasm detection by a next-generation sDNA test and effects of covariates on test performance. METHODS: We performed a blinded, multicenter, case-control study using archived stool samples collected in preservative buffer from 252 patients with colorectal cancer (CRC), 133 with adenomas >= 1 cm, and 293 individuals with normal colonoscopy results (controls); two-thirds were randomly assigned to a training set and one-third to a test set. The sDNA test detects 4 methylated genes, a mutant form of KRAS, and the alpha-actin gene (as a reference value) using quantitative, allele-specific, real-time target and signal amplification; it also quantifies hemoglobin. We used a logistical model to analyze data. RESULTS: The sDNA test identified 85% of patients with CRC and 54% of patients with adenomas >=1 cm with 90% specificity. The test had a high rate of detection for all nonmetastatic stages of CRC (aggregate 87% detection rate for CRC stages I-III). Detection rates increased with adenoma size: 54% >= 1 cm, 63% >1 cm, 77% >2 cm, 86% >3 cm, and 92% >4 cm (P < .0001). Based on receiver operating characteristic analysis, the rate of CRC detection was slightly greater for the training than the test set (P = .04), whereas the rate of adenoma detection was comparable between sets. Sensitivities for detection of CRC and adenoma did not differ with lesion site. CONCLUSIONS: Early-stage CRC and large adenomas can be detected throughout the colorectum and with high levels of accuracy by the sDNA test. Neoplasm size, but not anatomical site, affected detection rates. Further studies are needed to validate the findings in a larger population and optimize the sDNA test. PMID- 22062358 TI - Adalimumab induces and maintains clinical remission in patients with moderate-to severe ulcerative colitis. AB - BACKGROUND & AIMS: Adalimumab is a fully human monoclonal antibody that binds tumor necrosis factor (TNF)-alpha. Its efficacy as maintenance therapy for patients with ulcerative colitis has not been studied in a controlled, double blind trial. METHODS: Ulcerative colitis long-term remission and maintenance with adalimumab 2 (ULTRA 2) was a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of adalimumab in induction and maintenance of clinical remission in 494 patients with moderate-to-severe ulcerative colitis who received concurrent treatment with oral corticosteroids or immunosuppressants. Patients were stratified based on prior exposure to TNF-alpha antagonists (either had or had not been previously treated with anti-TNF-alpha) and randomly assigned to groups given adalimumab 160 mg at week 0, 80 mg at week 2, and then 40 mg every other week or placebo. Primary end points were remission at weeks 8 and 52. RESULTS: Overall rates of clinical remission at week 8 were 16.5% on adalimumab and 9.3% on placebo (P = .019); corresponding values for week 52 were 17.3% and 8.5% (P = .004). Among anti-TNF-alpha naive patients, rates of remission at week 8 were 21.3% on adalimumab and 11% on placebo (P = .017); corresponding values for week 52 were 22% and 12.4% (P = .029). Among patients who had previously received anti-TNF agents, rates of remission at week 8 were 9.2% on adalimumab and 6.9% on placebo (P = .559); corresponding values for week 52 were 10.2% and 3% (P = .039). Serious adverse events occurred in 12% of patients given adalimumab or placebo. Serious infections developed in 1.6% of patients given adalimumab and 1.9% given placebo. In the group given adalimumab, 1 patient developed squamous cell carcinoma and 1 developed gastric cancer. CONCLUSIONS: Adalimumab was safe and more effective than placebo in inducing and maintaining clinical remission in patients with moderate-to-severe ulcerative colitis who did not have an adequate response to conventional therapy with steroids or immunosuppressants. PMID- 22062359 TI - Tobacco smoking increases the risk of high-grade dysplasia and cancer among patients with Barrett's esophagus. AB - BACKGROUND & AIMS: Esophageal adenocarcinoma arises from Barrett's esophagus (BE); patients with this cancer have a poor prognosis. Identification of modifiable lifestyle factors that affect the risk of progression from BE to esophageal adenocarcinoma might prevent its development. We investigated associations among body size, smoking, and alcohol use with progression of BE to neoplasia. METHODS: We analyzed data from patients with BE identified from the population-based Northern Ireland BE register, diagnosed between 1993 and 2005 with specialized intestinal metaplasia (n = 3167). Data on clinical, demographic, and lifestyle factors related to diagnosis of BE were collected from hospital case notes. We used the Northern Ireland Cancer Registry to identify which of these patients later developed esophageal adenocarcinoma, adenocarcinomas of the gastric cardia, or esophageal high-grade dysplasia. Cox proportional hazards models were used to associate lifestyle factors with risk of progression. RESULTS: By December 31, 2008, 117 of the patients with BE developed esophageal high-grade dysplasia or adenocarcinomas of the esophagus or gastric cardia. Current tobacco smoking was significantly associated with an increased risk of progression (hazard ratio = 2.03; 95% confidence interval, 1.29-3.17) compared with never smoking, and across all strata of smoking intensity. Alcohol consumption was not related to risk of progression. Measures of body size were infrequently reported in endoscopy reports, and body size was not associated with risk of progression. CONCLUSIONS: Smoking tobacco increases the risk of progression to cancer or high-grade dysplasia 2-fold among patients with BE, compared with patients with BE that have never smoked. Smoking cessation strategies should be considered for patients with BE. PMID- 22062360 TI - A high-fiber diet does not protect against asymptomatic diverticulosis. AB - BACKGROUND & AIMS: The complications of diverticulosis cause considerable morbidity in the United States; health care expenditures for this disorder are estimated to be $2.5 billion per year. Many physicians and patients believe that a high-fiber diet and frequent bowel movements prevent the development of diverticulosis. Evidence for these associations is poor. We sought to determine whether low-fiber or high-fat diets, diets that include large quantities of red meat, constipation, or physical inactivity increase risk for asymptomatic diverticulosis. METHODS: We performed a cross-sectional study of 2104 participants, 30-80 years old, who underwent outpatient colonoscopy from 1998 to 2010. Diet and physical activity were assessed in interviews using validated instruments. RESULTS: The prevalence of diverticulosis increased with age, as expected. High intake of fiber did not reduce the prevalence of diverticulosis. Instead, the quartile with the highest fiber intake had a greater prevalence of diverticulosis than the lowest (prevalence ratio = 1.30; 95% confidence interval, 1.13-1.50). Risk increased when calculated based on intake of total fiber, fiber from grains, soluble fiber, and insoluble fiber. Constipation was not a risk factor. Compared to individuals with <7 bowel movements per week, individuals with >15 bowel movements per week had a 70% greater risk for diverticulosis (prevalence ratio = 1.70; 95% confidence interval, 1.24-2.34). Neither physical inactivity nor intake of fat or red meat was associated with diverticulosis. CONCLUSIONS: A high-fiber diet and increased frequency of bowel movements are associated with greater, rather than lower, prevalence of diverticulosis. Hypotheses regarding risk factors for asymptomatic diverticulosis should be reconsidered. PMID- 22062362 TI - Castration and slaughter age effects on nutritive value of the "mestico" goat meat. AB - Groups of castrated male and intact "mestico" goats were slaughtered at 175, 220, 265 and 310 days of age. After slaughter the carcasses were chilled for 24 h at 2 degrees C, and pH, Aw, Ca, Fe, P, moisture, ash, protein and fat were determined on the total lean. Slaughter age had a significant (p<0.01) effect on moisture, protein, iron, calcium and pH. Calcium content was influenced by castration and the slaughter age*castration interaction was significant (p<0.01) for iron content. Meat from castrated males contained less moisture and protein and more fat, ash, iron and calcium than did meat from intact males. The fat, protein and iron content increased with increasing slaughter age, while moisture decreased. Composite results indicate slaughtering "mestico" goats at 310 days exert favourable effects on the parameters investigated. (c) PMID- 22062361 TI - Helicobacter pylori infection recruits bone marrow-derived cells that participate in gastric preneoplasia in mice. AB - BACKGROUND & AIMS: Studies in animal models have shown that bone marrow-derived cells (BMDC) could be involved in the formation of carcinomas of the upper gastrointestinal tract, including gastric carcinoma. Most gastric carcinomas in humans have been associated with chronic infection with Helicobacter pylori; we investigated the bacteria's potential to induce premalignant lesions in mice and studied the kinetics of BMDC settlement in the gastric epithelium. METHODS: C57BL/6J female chimeric mice with BMDCs from male donors that express green fluorescent protein were infected with human-derived and mouse-adapted strains of H pylori and followed. We assessed development of pathologic features and recruitment of BMDC to the gastric mucosa using immunohistochemistry and fluorescent in situ hybridization analyses of gastric tissue sections. RESULTS: Infection of mice with different strains of H pylori led to the development of chronic inflammation, hyperplasia, and mucinous metaplasia, and, later in life, of pseudointestinal metaplasia and dysplasia. After 1 year, gastric glands that contained green fluorescent protein-positive male cells were detected in 50%-90% of female chimeric mice infected with H pylori strains; the presence of these glands correlated with the development of pseudointestinal metaplasia. Twenty-two percent of H pylori-induced dysplastic lesions were composed of glands that contained epithelial BMDCs. CONCLUSIONS: H pylori infection leads to development of chronic inflammation, hyperplasia, metaplasia, and dysplasia, as well as the recruitment and accumulation of BMDC in the gastric epithelial mucosa. Nearly 25% of dysplastic lesions include cells that originate from the BM. PMID- 22062363 TI - Expanded extrudates from corn starch-lamb blends: process optimization using response surface methodology. AB - A central composite second-order design was used to study the effects of feed (raw material blend) moisture, process temperature, and screw speed on expansion ratio (ER) and shear-force (SF) of extrudates from blends of corn starch and lean lamb. Quadratic polynomial equations were obtained by multiple regression analysis using response surface methodology. The predicted models were adequate when tested by the lack of fit and coefficient of determination. The validity of the models was also confirmed by experimental data. Regression analysis predicted an optimal (minimal) SF to be attained with 26.5% feed moisture, 148 degrees C process temperature, and 134 rpm screw speed. This process condition was used in a companion study to produce and compare extrudates from blends of corn starch and lamb or mutton with similar extrudates produced with other meats. (c) PMID- 22062364 TI - Composition, storage stability and sensory properties of expanded extrudates from blends of corn starch and goat meat, lamb, mutton, spent fowl meat, or beef. AB - Blends of corn starch (81.72-84.86%) and ground meat (goat meat, lamb, mutton, spent hen meat, beef 15.14-18.28%) were prepared for a target moisture level of 26.5% (with no added water) and cooked-puffed using a single-screw extruder. All extrudates were well expanded and low in fat (< 1.5%), a(w) (< 0.12), bulk density, and shear-force. Trained panel sensory scores indicated all products were bland, with no differences found in flavor attributes among products. The dominant flavor notes were "rice" and "dried grassy" (mean scores of 2.23-2.29 and 1.81-2.15, respectively, on a 0-15 scale). Most panelists did not perceive "meat" note or species-related meat flavor. Total polyunsaturated fatty acid percentage was similar for extrudates with beef, lamb and mutton and highest for those with chicken. When extrudates were stored aerobically at 37 degrees C for up to 120 days, lipid oxidation (as measured in meq. peroxides/kg fat) was lower for products containing goat meat, lamb, or mutton than for those with beef or chicken. The degree of polyunsaturation or unsaturation of their fat only partly accounted for the lipid oxidation differences. (c) PMID- 22062365 TI - Effects of high pressure treatments on intramuscular connective tissue. AB - The changes in the morphological structure and proteoglycan (PGs) extractability of the intramuscular connective tissues from bovine skeletal muscle exposed to high pressure (100~400 MPa) were investigated and compared to those in muscle during ageing. SDS-PAGE profiles of the PGs were also studied. During ageing, structural changes in the endomysium and perimysium occured, and disruption of the honeycomb-like structure of endomysium was observed. In the pressurized muscle, deformation of the honeycomb-like structure of endomysium was accelerated with increase of pressure applied to the muscle, and disruption of endomysium was observed in several places in the muscle pressurized at 400 MPa. Changes in the extractability of PGs were not observed in the pressurized muscle, whereas the extractability of PGs decreased with ageing. Changes in the density of the main component in the PGs with molecular mass of more than 3000 kDa on the SDS-PAGE were not observed in the PGs from the pressurized muscle, whereas the density of this band gradually decreased during the ageing. The decrease in the amounts of PGs extracted from the aged muscle seems to be due to degradation of the PGs into small dialysable molecules. From the results, it seems that high pressure treatment has some different effects on intramuscular connective tissue to ageing. (c) PMID- 22062366 TI - Effect of time of deboning and sample size on drip loss of pork. AB - The effects of time of deboning and sample size on drip loss of pork samples (m. longissimus) was studied in relation to the weight loss of the carcass sides or joints using two groups of 16 carcasses. One side of each carcass was cut and sampled at 1 day post mortem and served as a control. The other carcass sides were sampled for meat quality measurements after storage for another 5 days, either without cutting (group 1, n=16) or after cutting into primal joints (group 2, n=16). It was found that weight loss of carcass sides and joints increased with time, but at a decreasing rate. Drip loss largely decreased when meat samples were taken at a later time post mortem. The 48 h drip loss of the meat samples taken at 6 days post mortem was approximately 6% lower than in samples taken at 1 day post mortem. This reduction in drip loss was of the same magnitude as the weight loss of the carcass sides or the joints during 5 days storage. It is suggested that 'leaking out' explains most of the reduction in drip loss when sampling at a later time post mortem, and is not due to an improvement of water holding capacity of the meat. It was also found that standardising the sample size increased drip loss. The effect of sample size is discussed in relation to the carcass lean content. Storage had little or no effect on other meat quality traits. (c) PMID- 22062367 TI - The storage life of beef and pork packaged in an atmosphere with low carbon monoxide and high carbon dioxide. AB - Ground beef, beef loin steaks and pork chops were packaged in modified atmospheres of 0.4% CO/60% CO(2)/40% N(2) and 70% O(2)/30% CO(2). In addition ground beef was packaged in clipped chub packs, beef loin steaks were vacuum packaged, and pork chops were packaged in an atmosphere of 60% CO(2)/40% N(2) with each pack containing an O(2) absorber. The packs were stored in the dark at 4 or 8 degrees C for up to 21 days. Meat in 0.4% CO/60% CO(2)/40% N(2) had a stable bright red colour that lasted beyond the time of spoilage. The storage lives in this gas mixture at 4 degrees C, as limited by off-odours, were 11, 14 and 21 days for ground beef, beef loin steaks and pork chops, respectively. The 70% O(2)/30% CO(2) atmosphere resulted in an initially bright red to red colour of the meat, but the colour was unstable and off-odours developed rapidly. The off-odours probably were caused by Brochothrix thermosphacta, which grew in all meat types, or by pseudomonads in ground beef. Meat stored in chub packs, vacuum packs or 60% CO(2)/40% N(2) with an O(2) absorber developed off-odours and microflora similar to those of meat in 0.4% CO/60% CO(2)/40% N(2), but with less acceptable appearances. These results show that a low CO/high CO(2) atmosphere is effective for preserving retail-ready meat. (c) PMID- 22062368 TI - Oxidative and lipolytic changes during ripening of Iberian hams as affected by feeding regime: extensive feeding and alpha-tocopheryl acetate supplementation. AB - The effect of pig feeding in an extensive system based on acorn and pasture or in confinement with a control diet containing 5 mg alpha-tocopheryl acetate kg(-1) of feed and a 100 mg alpha-tocopheryl acetate kg(-1) enriched diet on evolution of lipid changes throughout ripening of dry-cured hams was investigated. Feeding regime significantly affected TBA-RS, peroxide value and hexanal content of Biceps femoris and Semimembranosus muscles. Muscles from pigs fed supplemented diet with alpha-tocopherol or fed extensively on acorn and grass showed significant lower (p<0.05) TBA-RS and peroxide value than ham muscles from pigs fed the basal diet at 210 days of processing. Both feedings reduced significantly (p<0.05) hexanal content at day 210 and day 700. Muscle slices from pigs fed on acorn showed significant higher scores (p<0.05) in aroma and flavour intensity, cured flavour and numerically lower rancid scores than those from control diet hams. (c) PMID- 22062369 TI - Partial least squares (PLS) regression for the analysis of instrument measurements and sensory meat quality data. AB - The partial least squares (PLS) regression technique was used to examine meat quality data derived from instruments (including Warner-Bratzler shear force and Instron Compression) and sensory panels. The data related to beef longissimus dorsi muscles collected during trials to study the effect of hot boning on meat quality. The univariate analysis of tenderness showed that over 60% of the variation in sensory tenderness, and almost 60% of the variation in sensory acceptability, could be explained from instrument variables and a consideration of boning and ageing time. Graphical displays from the analysis indicated that hot boning (either at 1 or 4 h) had little effect on meat quality. Graphical displays demonstrated a possible important effect of vacuum-pack ageing on acceptability. For this data set, it appears that samples of approximately equivalent tenderness differ in acceptability, depending on whether the samples have been aged for 1 or 4 weeks. This finding may have practical importance in attempts to predict eating quality (acceptability) from instrument measurements. Separate equations are necessary for products aged for different periods. (c) PMID- 22062370 TI - Electrical stimulation of pigs-effect on pH fall, meat quality and Cathepsin B+L activity. AB - This work was performed to evaluate the effect of electrical stimulation (ES) on pH fall and meat quality of LD and BF in Danish halothane free pigs stunned with CO(2). ES resulted in a significant drop in pH of 0.3 units in both LD and BF and 3 h lairage resulted in 0.1 units lower pH at 20 min post mortem. Lairage time did not affect and did not interact with the effect of ES on any of the measured meat quality parameters. ES did not affect the ultimate pH in LD, BF, SM and SC or internal reflection value in LD. However, ES caused higher internal reflection and drip loss in BF and increased the PSE frequency in LD (2 to 7%) and in BF (2 to 49%). The frequency of PSE areas in the centre of SM was 70% for ES pigs compared to 9% for control pigs. ES and ageing improved the tenderness and reduced the hardness in LD as well as shear force of unaged BF. The effect of ES on tenderness and hardness was approximately half the effect of ageing, but the effect of ES and ageing were additive. ES significantly increased the activities of cathepsin B+L in the myofibrillar fraction, but there were no differences in proteolytic activity in the other fractions. It is concluded that ES improves tenderness in LD and BF, but has a negative effect on the quality of BF and SM. Therefore ES is not an economically attractive alternative for improvement of tenderness in LD compared to ageing in Danish pigs. (c) PMID- 22062371 TI - Effect of muscle type, salt and pH on cooked meat haemoprotein formation in lamb and beef. AB - The rate of cooked meat haemoprotein formation, measured as the rate of loss of myoglobin solubility, in lamb was dependent on the muscles anatomical location and temperature. Lamb longissimus dorsi musle at 55 to 70 degrees C formed cooked meat haemoprotein more rapidly than the muscles in the shoulder and leg. The formation in lamb was more rapid than in beef. The rate in high pH beef (7.25) l. dorsi was lower than found in beef l. dorsi of normal pH but in low pH lamb (5.38) l. dorsi the rate was, at most temperatures, also slower than found in this muscle from lamb of normal pH. In the presence of NaCl the rate of cooked meat haemoprotein formation was faster (almost doubled at 2g/100g meat) than found in the corresponding salt free lamb and beef samples. Other additives commonly added to meat products (mechanically recovered meat, oil, polyphosphates, soya, whey and caseinate) had little effect on the rate of cooked meat haemoprotein formation, at the levels normally used in meat products. It is concluded that for lamb products little if any myoglobin will remain soluble, and the products will look cooked before the recommended thermal treatment to inactivate Escherichia coli O157:H7 has been achieved. (c) PMID- 22062372 TI - Effect of slaughter weight and/or age on histological characteristics of pig longissimus dorsi muscle as related to meat quality. AB - The effect of increasing both weight and age or age alone through feed restriction on muscle longissimus dorsi histological characteristics were studied in relation to fresh and cooked meat quality. Starting at 83 days (32 kg) 80 crossbred Duroc * (Large White*Landrace) barrows were allotted within litter to 4 experimental groups (A100, R100, A130, R130). Pigs were fed either ad libitum (A) or were restricted 30% (R) and slaughtered either at 100 kg or 130 kg. Muscle fibres were classified as betaR, alphaR or alphaW according to Ashmore and Doerr (1971)(Ashmore, C.R., & Doerr, L. (1971). Comparative aspects of muscle fibre types in different species. Experimental Neurology, 31, 408-418.). Percentages (PC), cross-sectional areas (CSA) and relative areas (RA) of each fibre type were evaluated. Phenotypic correlations between histological traits showed that RA of a particular fibre type depends essentially on its numerical abundance. Increasing weight together with age led to enlargement of betaR and alphaW muscle fibres, without changing muscle histochemical profile. When age was increased at the same weight (restriction), higher RA of betaR fibres was observed. Low, but significant correlation between loin eye area and CSA was observed, but not within experimental group. The phenotypic correlations between histological and meat quality traits were generally low. This material showed some significant correlations suggesting that increasing PC or CSA of overall alphaW fibres can be beneficial for water holding capacity of fresh meat and juiciness of cooked meat. (c) PMID- 22062373 TI - The effect of increasing carcass weight of finishing boars and gilts on joint composition and meat quality. AB - Two hundred and eighty-eight crossbred (3/4 Landrace * 1/4 Large White) pigs, comprising equal numbers of boars and gilts, were housed in single sex groups from 50 kg liveweight to slaughter at liveweights of 92, 105, 118 and 131 kg (carcass weights of 70, 80, 90 and 100 kg). Sample joints from the left longissimus dorsi muscle were obtained at slaughter for dissection and meat quality assessment. As carcass weight increased there were significant (p<0.001) increases in eye muscle area and subcutaneous fat content. Lean content decreased (p<0.001) with increasing carcass weight while intermuscular fat content was not affected. There was a significant interaction between carcass weight and gender with % drip loss in pork from gilts at 100 kg having a higher drip loss than boars and gilts at all other weights. There were small but significant (p<0.01) reductions in ultimate pH with increasing carcass weight. Cooking loss was also reduced (p<0.001) at the heavier weights. There was no effect of carcass weight on shear force or on intramuscular fat. Dry matter (DM) and crude protein (CP) contents of m. L. dorsi increased (p<0.001) at heavier weights while sarcomere length decreased (p=0.001). Compared with boars, gilts had greater eye muscle area (p<0.05), more subcutaneous fat (p<0.001). Meat from gilts in comparison with boars had higher % DM and % CP contents (p<0.001), higher intramuscular fat content and shear force (p<0.05). It is concluded that meat quality may be improved when carcass weight is increased from 70 to 100 kg. (c) PMID- 22062374 TI - Membrane lipid oxidation and proteolytic activity in thigh muscles from broilers fed different diets. AB - The effects of diets differing in their level of unsaturation and their contents of natural antioxidants and prooxidants on lipid oxidation was measured in microsomal membranes of the thigh muscles of broilers by three processes: enzymatic, nonenzymatic and sarcoplasmic protein oxidation. Lysosomal cysteine proteinase activities were determined to assess the influence of the different diets on the enzymatic proteolysis of meat. Statistically significant differences were found in the enzymatic reaction for 72 h of incubation at 4 degrees C in relation to the effect of both diet and antioxidant supplementation. Meat from animals fed an unsaturated diet containing sunflower oil gave the highest level of oxidation. Broilers fed supplemental antioxidants, especially alpha tocopherol, had lower degrees of oxidation than those fed the basal diet. An unexpected result of the prooxidant diet study was a higher degree of oxidation in samples from animals deprived of iron and copper. Cysteine proteinase activities were favoured by vitamin E (alpha-tocopherol) supplementation and the absence of copper. (c) PMID- 22062375 TI - Influence of sex and slaughter weight on carcass and meat quality in light and medium weight lambs produced in intensive systems. AB - Effects of slaughter weight and sex on carcass characteristics and lamb meat quality of Manchega Spanish breed were analysed. Forty-five lambs were divided into two slaughter weight groups: light (LW=21.7+/-0.16 kg; n=24) and medium (MW=27.8+/-0.16 kg; n=21). Dressing proportion and conformation were significantly different between groups and sex. There were also differences between light and medium group in fatness but not between males and females. Water holding capacity decreased with increasing slaughter weight (p<0.05) and was lower in females than in males (p<0.001). The increase in weight was associated with a decrease in L* (p<0.01), while a* showed an increase which failed to reach statistical significance. Slaughter weight and sex affected neither pH and its decrease post-slaughter nor meat toughness. (c) PMID- 22062376 TI - Optimization of the still-marinating process of chicken parts. AB - The still-marinating process is a simplified technology used to tenderize and to improve the flavor and succulence of meat to satisfy consumer demand. The objective of this study was to obtain still-marinated chicken breast meat and legs of good quality. To attain this aim, the effects of salt concentration, polyphosphates concentration and marinating time were optimized to increase weight gain, reduce loss of weight during storage and reduce cooking loss, making use of the surface response methodology. The results of this study indicate that marinating times ranging from 8-12 hours, salt concentrations ranging from 3-4% and polyphosphates concentration ranging from 2-3% are recommended for the still marinating process of chicken breast meat. In additon, marinating times ranging from 4-8 hours, salt concentration ranging from 3-4% and polyphosphates concentration of about 2% can be suggested for the still-marinating process of chicken legs. (c) PMID- 22062377 TI - Stable and convenient spatial registration of stand-alone NIRS data through anchor-based probabilistic registration. AB - For functional neuroimaging with near-infrared spectroscopy (NIRS), we recently introduced a probabilistic registration method that uses a reference magnetic resonance image (MRI) database instead of the subject's own MRI, and probabilistically registers the NIRS optode or channel positions onto a canonical brain template in the standard stereotactic brain coordinate systems. As an alternative method, we devised an anchor-based registration method utilizing roughly obtained anchor positions on the scalp instead of strictly defined landmarks such as 10/20 landmarks. This method uses a spherical coordinate system to seek a position in the reference MRI database that corresponds to the anchor position, and eventually presents NIRS optode and channel positions in the standard stereotactic brain coordinate system. For comparison against conventional probabilistic registration, we simulated NIRS optode holder placement on 100 synthesized virtual heads, and found holistic tendencies for probe position estimations were similar between the two methods. Comparison among anchor-based probabilistic registration, conventional probabilistic registration, and SPM-based registration via co-registration to a subject's own MRI revealed that intra-method variability was comparable to a small inter-method variability. Thus, anchor-based registration is a practical alternative, especially to avoid burdening a subject and to reduce experimental time. PMID- 22062378 TI - Effect of pre-slaughter rations of forage and/or concentrates on the composition and quality of retail packaged beef. AB - Continental Limousin and Charolais crossbred steers (n=66) were assigned to one of six diets: (1) high herbage allowance (18 kg grass dry matter), zero concentrate (HH0C), (2) high herbage allowance and 2.5 kg concentrate (HHLC), (3) high herbage allowance and 5 kg concentrate (HHHC), (4) low herbage allowance (6 kg grass DM) and 5 kg concentrate (LHHC), (5) medium herbage allowance (12 kg grass DM) and 2.5 kg concentrate (MHLC) or (6) concentrates ad-libitum+1 kg straw (CON). Colour was assessed in steaks (n=5) chosen at random from each dietary group and held in overwrapped and/or modified atmosphere packaging (MAP) (80 O(2):20 CO(2)) under simulated retail display conditions for 17 days. When the HH0C and the CON groups were compared, there was no significant difference in colour under overwrapped conditions, however under MAP, surface redness was significantly (P<0.01) higher (greatest Hunter "a" values) in the HH0C group. When the other four diets were compared to the HH0C and CON groups, there was no significant difference in colour under both forms of packaging. Lipid oxidation was highest for the dietary group CON compared to all other dietary groups examined. There was no significant difference in vitamin E levels between the six dietary groups, levels ranged from 1.7 to 2.5 MUg/g meat. PMID- 22062379 TI - Optimization of instrumental colour analysis in dry-cured ham. AB - Colour of dry cured ham was measured by instrumental techniques in order to determine the optimum measurement index. Five different colour systems were used: CIE L(*)a(*)b(*), Hunter Lab, CIE L(*)u(*)v(*), xyY and XYZ, each with illuminants D65, C and A, and with both 10 and 2 degrees observer angles. Measurements were taken in both Semimembranosus (SM) and Biceps femoris (BF) muscles. Hunter Lab system with illuminant A gave the most reproducible results within muscles for the three colour parameters evaluated. A further comparison of results obtained with 10 and 2 degrees observer angles of Hunter Lab with illuminant A showed there were no significant differences between the angles. Significant differences between results from SM and BF muscles were found in all the hams, the BF always showing higher values than SM for every colour parameter. PMID- 22062380 TI - Variation of the sensory quality within the m. longissimus thoracis et lumborum of PSE and normal pork. AB - This study evaluated the variation in instrumental and sensory meat quality within the m. longissimus thoracis et lumborum of carcasses with normal and PSE meat. Out of 80 slaughtered pigs, respectively, 9 and 7 carcasses were selected with a pH30 value > or=5.80 (normal pork) and a pH30 value <5.80 (PSE pork). Instrumental and sensory meat quality measurements were performed at three locations on these carcasses: longissimus thoracis (LT), longissimus thoracis et lumborum: (LTL-mid-loin) and longissimus lumborum (LL). Meat of the thoracis site (LT) was paler, but more favourable for pH45, cooking loss, juiciness, tenderness and preference scores than meat of the mid-loin part. The lumborum site (LL) was more or less in between the other two locations for meat quality, but closer to the LTL than the LT site. The meat quality variation within the m. longissimus thoracis et lumborum followed a similar pattern for normal and PSE carcasses. It can be concluded that the mid-loin part is best suited as a reference place for meat quality assessment, if one wants to eliminate carcasses with unacceptable meat. PMID- 22062381 TI - Changes in structure and color characteristics of irradiated chicken breasts as a function of dosage and storage time. AB - Structural change and color characteristics of chicken breasts as a function of irradiation dose and subsequent storage process were investigated by visible spectroscopy and HunterLab measurement. Ratios of R(1)=A(485 nm)/A(560 nm) and R(2)=A(635 nm)/A(560 nm,) which are related to absorbances of the visible bands at 485 nm (metmyoglobin), 560 nm (oxymyoglobin), and 635 nm (sulfmyoglobin), suggested that relative amount of oxymyoglobin either increases as a result of irradiation, or decreases with the storage process. The plot of R(1) and R(2) versus storage time showed that the increments of both R(1) and R(2) are dose dependent and that the relative amount of oxymyoglobin species in irradiated meats begins to decompose 7-12 days later than raw meats. In addition, R(1) and R(2) values were correlated with color index E(*) of chicken breasts. PMID- 22062382 TI - Effect of breed-type on performance and carcass traits of intensively managed hair sheep. AB - The objectives of this study were to evaluate growth performance and carcass characteristics of intensively managed purebred and crossbred hair sheep, and determine the value of the Dorper breed as a terminal sire on St.Croix and St. Croix-cross dams. Animals used were Dorper*St. Croix (DS), and Dorper*Romanov*St. Croix (DX), Katahdin (KA), St. Croix (SC), and 3/4 St. Croix-1 4 Romanov (SX) wether lambs. From birth to weaning, daily gains (ADG) were greater (P<0.01) for DS and KA lambs than SC and SX lambs; yet, from weaning to harvest, ADG was greatest (P<0.01) for DS, followed by DX, SC, SX, and KA lambs. Carcass weights were heavier (P<0.01) for DS than all other breeds and DS, DX, KA, and SX carcasses had greater (P<0.01) fat thickness measurements than SC carcasses. The longissimus thoracic (LT) area was largest (P<0.01) for DS and DX carcasses and smallest (P<0.01) for SC and SX carcasses. Skeletal, lean, and overall maturities were similar (P>0.10) among the breed types; however, carcasses from SC lambs received lower (P<0.02) flank streaking scores than DS, KA, and SX lambs. Conformation scores and quality grades were greater (P<0.01) for DS and DX than SC or SX carcasses. Although L* values of the LT were similar (P>0.10), the LT from DX lambs was redder (P<0.01) and more yellow (P<0.01) than that of DS and SC lambs. The shear force values of the LT chops from KA lambs were greater (P<0.01) than all other breed types. Results indicate that improvements in live animal performance, carcass muscularity, and quality can be achieved by using Dorper sires on purebred and crossbred St. Croix dams. PMID- 22062383 TI - Binding and textural properties of beef gels processed with kappa-carrageenan, egg albumin and microbial transglutaminase. AB - The combined influence of kappa-carrageenan (kappa-CGN, 0.5%) and egg albumin (EA, 2%) on quality characteristics of beef gels processed without or with 0.5% microbial transglutaminase (MTG) was investigated. Beef gel properties were determined by measuring textural, hydration and colour characteristics. kappa Carrageenan favourably affected hydration properties and thermal stability, yielding lower cooking loss, purge and expressible moisture. It also increased hardness and fracturability of beef gels, but was unable to improve springiness or cohesiveness. Egg albumin either alone or in combination with MTG generally has been found to be inferior to kappa-carrageenan for functionality in comminuted meat systems. Addition of EA produced an increase in lightness and yellowness, and a decrease in redness of beef gels, while the presence of kappa carrageenan resulted in lower L(*) and b(*), and higher a(*) values. No significant influence of MTG on gel colour parameters was observed. PMID- 22062384 TI - Measuring the effects of phenotype and mechanical restraint on proteolytic degradation and rigor shortening in callipyge lamb longissimus dorsi muscle during extended aging. AB - The purpose of this study was to determine if tenderness of callipyge (CLPG) longissimus dorsi muscle (LM) could be improved by: (1) extending the aging period to 48 days postmortem or (2) preventing rigor shortening by clamping. In CLPG and normal (NML) chops respectively, initial Warner-Bratzler shear values (WBS) were lower (P<0.05) in clamped (CL) (5.5 and 3.6 kg) compared to unclamped (UCL) (7.4 and 4.9 kg) LM. In CLPG, an acceptable WBS (3.6 kg) was reached at 48 days PM, whereas, NML lambs reached an acceptable level (3.8 kg) by 3 days PM. Sarcomere lengths (SL) of CL (1.68 MUm) were longer (P <0.05) than for UCL (1.44 MUm) and were negatively correlated with WBS (r=-0.55; P<0.1). The appearance of Troponin-T (TNT) degradation product coincided with tender WBS values; 3 days postmortem in NML UCL and 48 days postmortem in CLPG. In conclusion, clamping reduced WBS possibly by reducing rigor shortening. Extended aging resulted in CLPG LM with acceptable WBS values, concurrent with the appearance of TNT degradation products. PMID- 22062385 TI - Sensory and functional meat quality characteristics of pork derived from three halothane genotypes. AB - The effect of the halothane gene in pigs on the meat and sensory qualities thereof were determined. Meat derived from 60 Landrace*Large White pigs of three halothane genotypes was used. The sensory qualities, cooking loss, colour, shear value and proximate analysis of the cooked pork loin roasts were determined. The three genotypes did not differ significantly (P>0.05) with regard to the colour of the cooked meat, percentage cooking loss and percentage moisture. There were significant differences (P<0.05) between the genotypes in the percentage protein, ash and fat. Meat from the three genotypes also differed significantly (P<0.05) in juiciness, an analytical sensory panel scored the juiciness of meat from the NN-genotype the highest with a value of 71.3 when using a structured line scale. Meat from the nn-genotype had the lowest score for juiciness (62.8). Meat from the three genotypes did not differ significantly (P>0.05) with regard to tenderness, pork flavour and no mealiness. Correlation values showed a positive correlation (r=0.46, P<0.05) between juiciness and tenderness. These results indicate that the inclusion of the halothane gene in pig production programmes results in meat with an inferior quality and it can be recommended to exclude the halothane positive genotype from any pig production system where fresh pork quality is considered a primary goal. PMID- 22062386 TI - Chemical sprays as a method for improvement in microbiological quality and shelf life of fresh sheep and goat meats during refrigeration storage (5-7 degrees C). AB - The shelf-life of meats from freshly slaughtered sheep and goat carcasses at 5-7 degrees C was extended after spraying (pressure 3 kg/cm(2)) the carcasses with solution 'B' containing potassium sorbate, sodium acetate, sodium citrate, sodium lactate each at 2.5% and sodium chloride at 5% (prepared w/v in potable water), when compared with solution 'A' (without potassium sorbate). Solution B treatment inhibited Bacillus spp. to minimum and were not detected up to sixth day. It extended the lag phase of all organisms including psychrotrophes (pseudomonads) and reduction of differential counts in sheep and goat meat were noted throughout the refrigerated storage. On sixth day (control) and seventh day (solution "A treated") meat samples developed off odour and discoloration with total viable count (TVC)>10(7) cfu/g. Solution B treated meat samples showed no spoilage at seventh or eighth day, indicating an extended shelf-life of 3 and 2 days when compared with control and solution A treated meat, respectively. PMID- 22062387 TI - Carcass and meat quality in double-muscled Belgian Blue bulls and cows. AB - Carcass and meat quality of 37 bulls and 91 cows of the Belgian Blue breed (double-muscled type) were compared. Age at slaughter averaged 648+/-73 and 1820+/-689 days, respectively. Both groups of cattle were finished on maize silage supplemented with concentrate, and were slaughtered at about 750 kg live weight. Females had a lower (P=0.004) cold carcass weight (469.7 kg) in comparison with bulls (500.8 kg), due to a reduced dressing percentage (63.8 vs. 66.6; P <0.001). SEUROP conformation was better for bulls. SEUROP fat covering (P=0.007) and fat content in the carcass (16.4 vs. 12.9%; P <0.001) and in the M. longissimus thoracis (LT) muscle (2.3 vs. 1.1%; P <0.001) were higher for females than for males. The LT of cows was darker (lower L* and higher a*-value; P <0.001), had a better waterholding capacity (P?0.063) and was slightly more tender (P=0.120) than the LT of bulls. Increasing parity reduced dressing percentage and increased LT lightness (L*-value) in cows. Several carcass (SEUROP grading, composition, LT-area) and meat quality traits (protein and fat contents, drip and cooking losses, a*-value) were better correlated with carcass weight than parity. It is concluded that meat quality of the aged LT of cows is not negatively affected by age, while some carcass quality traits decreased with advancing age. Carcass quality traits adjusted for age at slaughter were better for bulls, but LT meat quality characteristics were at least as good for females as for males. PMID- 22062388 TI - Effect of transport time on sensorial aspects of beef meat quality. AB - Forty-eight slaughter bulls were transported by road in groups of eight for approximately 30 min, 3 h and 6 h in two replicates. After slaughter and an ageing time of 7 days, steaks from the longissimus dorsi thoracis were tasted by a trained sensory panel in terms of odour, tenderness, residue, juiciness, flavour intensity, flavour quality, and overall liking. Transport time had a significant effect (P<0.05) on meat tenderness and overall liking. The panel preferred meat from animals given the 3-h journey as opposed to the 30 min or 6-h journey and found it was more tender and had a better overall liking. PMID- 22062389 TI - Estimation of Canadian and European lean yields and composition of pig carcasses by dual-energy X-ray absorptiometry. AB - Dual-energy X-ray absorptiometry (DEXA) was used on 110 pig carcasses to estimate fat, lean, bone mineral content and total tissue masses of the major primal cuts and overall carcasses. The DEXA estimations were compared and used to predict the dissected lean, fat (including skin), bone and weight of primal cuts and carcasses, as well as to predict the Canadian and the European lean yields. The best relationships were obtained when predicting the weight of ham (R(2)=0.99), loin (R(2)=0.99), shoulder (R(2)=0.96), belly (R(2)=0.93), half carcass (R(2)=0.98), ham lean (R(2)=0.89), loin lean (R(2)=0.89), shoulder lean (R(2)=0.87), and the meat weight used in the estimation of the Canadian (R(2)=0.92) and the European lean yield (R(2)=0.82). While the weight of fat in the carcass and primal cuts was accurately estimated by DEXA (R(2)>0.72), DEXA carcass composition estimations were less accurate when predicting dissected bone weights (R(2)<0.54). PMID- 22062390 TI - Modelling the effect of fatty acids in odour development of cooked meat in vitro: part I-sensory perception. AB - We have investigated the contribution of muscle components to the development of cooked meat odour in an aqueous model system using trained taste panels. Reaction mixtures were prepared with oleic, linoleic and linolenic acids with or without cysteine and ribose in a buffer with or without ferrous sulphate. Odour profiles were assessed and triangular tests were used to determine the ability of panellists to discriminate between mixtures. The presence of sugar and amino acid was highly detectable by panellists independently of the fatty acid considered (P<0.001). However, the presence of C18:3 made differences more obvious between mixtures than the presence of C18:1 or C18:2. 'Meaty' notes were only associated with cysteine and ribose. 'Fishy' notes were only apparent in C18:3 mixtures with or without sugar and amino acid, although the presence of cysteine and ribose decreased the perception. The addition of Fe(++), a pro-oxidant present in the muscle, produced a reduction in the score of the attributes although the pattern was the same as when Fe was not used in the mixtures. Only 'fishy' notes that were exclusively perceived in C18:3 mixtures showed a higher score in the presence of iron. Iron also produced a better discrimination in C18:3 mixtures, which were closely related to 'grassy' notes in the presence of cysteine and ribose. PMID- 22062391 TI - Lipid peroxidation-derived cytotoxic aldehyde, 4-hydroxy-2-nonenal in smoked pork. AB - The contents of 4-Hydroxy-2-nonenal (HNE), cytotoxic aldehyde, in smoked meat products (ham, bacon and sausage) were analyzed. All the samples analyzed contained HNE, although large differences in the contents between the different samples were observed. In one lot of ham (H1) and wiener sausage (WS1) a high level in HNE was observed. The changes of HNE contents of pork meats containing 0, 0.1, 0.5 and 1% Sugi wood vinegar (SWV) stored at 0 degrees C were also analyzed for 7 days. As an index of lipid peroxidation level, malonaldehyde (MA) contents were also analyzed in these samples. After 7 days of storage, HNE was detected only in pork meats containing 1% SWV and the level was similar to those of H1 and WS1. Judging from MA contents, SWV may act as a pro-oxidant in pork meats and HNE may accumulate in pork in which lipid peroxidation is in progress. PMID- 22062392 TI - A comparative study of boar taint in cooked and dry-cured meat. AB - A comparative study of boar taint in cooked and dry-cured pig meat products was performed. Forty-eight cooked loins and 48 dry-cured hams from entire males and castrates were studied. The samples were classified according to the androstenone (AN) and skatole (SK) fat content determined using HPLC. A trained sensory panel evaluated taste, aroma, boar odour, boar flavour, juiciness, tenderness and fatness in cooked and dry-cured samples. Threshold levels of AN and SK to separate (P<0.05) entire and castrate samples according to their boar odour and flavour were determined. The effects of castration and processing on the eating quality were studied. Finally, the relationships among boar taint and other sensory attributes in cooked and dry-cured meat were compared. Results from these studies show that the eating quality of processed meat was affected negatively by boar taint. Threshold values were higher in dry-cured ham (2 MUg g(-1) AN and 0.12 SK) than cooked loin (0.5 AN and 0.1 SK). AN and SK had a synergistic effect on boar odour and flavour in both products. AN had a greater influence than SK on the aroma and taste, especially in cooked meat. Boar odour was perceived more intensely than boar flavour in both of the products studied. Castration favoured fatness and improved the aroma and taste of cooked and dry-cured meat. The loss of aroma and taste due to boar taint was more noticeable in cooking than drying and curing. In dry-cured meat boar taint was associated with less aroma, taste, juiciness and tenderness. However, in cooked meat, boar taint affected the aroma and taste more strongly, but was not related with juiciness and tenderness, probably because these attributes are influenced by cooking. PMID- 22062393 TI - Combination of aerobic and vacuum packaging to control lipid oxidation and off odor volatiles of irradiated raw turkey breast. AB - Effects of the combination of aerobic and anaerobic packaging on color, lipid oxidation, and volatile production were determined to establish a modified packaging method to control quality changes in irradiated raw turkey meat. Lipid oxidation was the major problem with aerobically packaged irradiated turkey breast, while retaining characteristic irradiation off-odor volatiles such as dimethyl sulfide, dimethyl disulfide, and dimethyl trisulfide was the concern for vacuum-packaged breast during the 10-day refrigerated storage. Vacuum packaging of aerobically packaged irradiated turkey breast meat at 1 or 3 days of storage lowered the amounts of S-volatiles and lipid oxidation products compared with vacuum- and aerobically packaged meats, respectively. Irradiation increased the a value of raw turkey breast, but exposing the irradiated meat to aerobic conditions alleviated the intensity of redness. PMID- 22062394 TI - Effects of quality grade on the chemical, physical and sensory characteristics of Hanwoo (Korean native cattle) beef. AB - The effects of quality grade (which reflects relative marbling) on the chemical, physical and sensory properties was investigated using Korean native cattle (Hanwoo) beef. Thirty-six Hanwoo cows were slaughtered and the carcasses were graded at 24h postmortem according to the Korean carcass grading system. The quality grade 1 (high quality), grade 2 and grade 3 (low quality) were based on the marbling score of longissimus dorsi (LD) muscles. The effects of quality grade on the meat quality parameters of beef LD muscle were assessed during aging. Loin-eye area, fat thickness and yield grade were all similar for the three quality groups. Mean lean color, fat color and maturity scores did not differ among quality grade groups (P>0.05). pH, Sarcomere length, WHC, collagen content, cooking loss, shear force and MFI were not affected by quality grade groups. Drip loss for grade 1 group was significantly lower than that for grade 3 groups (P<0.05). At initial tenderness evaluation of steaks, no differences among the three grades were observed; however, with additional days of storage, grade 1 steaks had higher tenderness score than grade 3 steaks (P<0.05). Increased postmortem aging time improved tenderness attributes regardless of quality groups. No significant differences were found among the quality grade groups for flavor (P>0.05). The grade 1 group had the highest juiciness score, and grade 3 groups had the lowest score (P<0.05), but postmortem aging did not influence flavor and juiciness. The quality grades were more strongly related to juiciness than tenderness or flavor. PMID- 22062395 TI - Effect of citric acid on the radiation resistance of Listeria monocytogenes and frankfurter quality factors. AB - Listeria monocytogenes is a common contaminant of ready-to-eat meat products, including frankfurters. Ionizing (gamma) radiation can eliminate L. monocytogenes from frankfurters. Citric acid (CA) is an antioxidant synergist and anti microbial agent that can be applied to the surfaces of cured meat products prior to packaging. The effect of CA on the radiation resistance of L. monocytogenes that was surface-inoculated onto frankfurters was determined. The D(10) values, the radiation doses required to inactivate 90% of viable L. monocytogenes, were 0.61, 0.60, 0.54, and 0.53 kGy, on frankfurters dipped in 0, 1, 5 or 10% CA solution, respectively. CA, although an antioxidant synergist, did not increase antioxidant activity (AA) on frankfurter surfaces as determined by the ferric reducing antioxidant power (FRAP) assay. Lipid oxidation, as determined by the Thiobarbituric acid reactive substances (TBARS) assay, was not affected by CA or ionizing radiation. Color of frankfurters, determined by Hunter L, a, b, indicated that ionizing radiation induced a small, but visually imperceptible, loss of redness (a-value). Frankfurter firmness, as measured by maximum shear force, was not affected by ionizing radiation or CA. CA enhanced the lethality of ionizing radiation without negatively impacting frankfurter color, lipid oxidation, firmness, or antioxidant activity. PMID- 22062396 TI - Effect of microbial transglutaminase and sodium caseinate on quality of chicken doner kebab. AB - The effect of microbial transglutaminase (MTGase) and sodium caseinate on the quality of chicken doner kebab was investigated. Yield, color, pH, SDS polyacrylamide gel electrophoresis (SDS-PAGE), texture, and sensory evaluations were measured. The results of SDS-PAGE showed that addition of MTGase with or without sodium caseinate created cross-linking between meat proteins. Texture measurements indicated that the effect of the enzyme on binding properties of chicken meat is more effective if it is used with sodium caseinate (P<0.05). Sensory evaluation was not significantly different statistically among treatments. PMID- 22062397 TI - Effect of Carnobacterium piscicola on aroma formation in sausage mince. AB - The metabolites from leucine degradation play a key role in sausage aroma. Leucine catabolism is particularly important in Carnobacterium piscicola. The purpose of the study was to determine the effect of C. piscicola inoculation on the aroma of a sausage model and on leucine catabolism. Sensory analysis and implantation of Carnobacterium were performed. Aromatic compound production from (3)H leucine added to the sausage model was measured by high-performance liquid chromatography. After 18 days of ripening, the level of Carnobacterium species was 10-fold higher in sausages inoculated with C. piscicola than in the control sausages. Addition of C. piscicola enhanced the development of sausage aroma. The leucine was 10% more degraded in the models inoculated with C. piscicola. 3 Methyl butanoic acid was the main metabolite detected and the highest production of alpha-ketoisocaproic acid and hydroxy alpha-ketoisocaproic acid were detected in the sausage model inoculated with C. piscicola. PMID- 22062399 TI - Retropharyngeal hematoma from parathyroid hemorrhage in a hemodialysis patient. AB - A case of a spontaneous retropharyngeal hematoma in a patient on chronic hemodialysis is described. A 75-year-old man presented with a 5-day history of throat discomfort and neck swelling. He had been on hemodialysis for chronic renal failure with secondary hyperparathyroidism. Examination showed a massively enlarged neck and bruising on his left neck and anterior chest. Flexible nasopharyngoscopy revealed bluish bulging of the posterior pharyngeal wall, and CT showed widening of prevertebral soft tissue. Hemodialysis reduced the swelling of the posterior pharyngeal wall, and conservative management including steroids and antibiotics was adequate for managing the airway and hematoma. Retropharyngeal swelling of this patient seemed to be derived not only from the hematoma itself, but also from the lymphatic and venous congestion. Follow-up CT and MRI indicated that the enlarged left parathyroid was the bleeding source. To the best of our knowledge, this is the second report of a retropharyngeal hematoma from parathyroid hyperplasia in a chronic hemodialysis patient. Physicians should be aware that rare parathyroid hemorrhage in chronic hemodialysis patients could lead to airway obstruction by retropharyngeal swelling. PMID- 22062400 TI - Neurally mediated syncope presenting with paroxysmal positional vertigo and tinnitus. AB - A 72-year-old man with positional vertigo and tinnitus was referred to us. He did not want to perform provoking test except once due to his fear. No positional nystagmus was provoked. He found that his attacks usually occurred when he lay on his right ear. From his clinical history, benign paroxysmal positional vertigo was suspected. Conventional pharmacotherapy as well as non-specific physical therapy did not have significant effect. His feeling of positional vertigo with pyrosis was actually presyncope. We suspected cardiovascular disorders, and referred him to a cardiologist. Portable cardiogram monitoring revealed paroxysmal bradycardia. He was diagnosed with neurally mediated syncope, and a pacemaker was implanted. His paroxysmal dizziness soon disappeared. It is important to study the clinical history of the patients in detail, as they are not always able to accurately explain their symptoms. We should carefully rule out cardiovascular disorders, especially when we see the patients with suspected BPPV without the characteristic positional nystagmus. PMID- 22062401 TI - Ascorbic acid minimizes lumbar vertebrae discoloration. AB - Ascorbic acid was evaluated as a way of preventing bone discoloration. In experiment 1, beef bone-in t-bone steaks (lumbar vertebrae and longissimus) were treated with 0%, 0.05%, 0.1%, 0.5%, 1.0%, or 1.5% ascorbic acid (n=10). Vertebrae and muscle color (L(*)a(*)b(*)) were evaluated initially and after 24 h in 80% O(2)/20% CO(2). Vertebrae treated with 0%, 0.05%, or 0.1% ascorbic acid significantly discolored while the longissimus maintained a bright-red appearance. Ascorbic acid treatments 0.5%, 1.0%, and 1.5% significantly minimized vertebrae discoloration and neither induced nor prevented longissimus discoloration. In experiment 2, lumbar vertebrae were treated with 0%, 0.05%, 1.5%, or 2.5% ascorbic acid (n=15), packaged in 80% O(2)/20% CO(2), and displayed for five days (1 degrees C). Visual color was evaluated daily by a trained panel. Ascorbic acid treatment at 1.5% or 2.5% minimized lumbar vertebrae surface discoloration. Through a five-day display at 1 degrees C, lumbar vertebrae with 2.5% ascorbic acid had the least bone discoloration. PMID- 22062402 TI - High pressure/thermal treatment effects on the texture of beef muscle. AB - The effects of high pressure (to 800 MPa) applied at different temperatures (20 70 degrees C) for 20 min on beef post-rigor longissimus dorsi texture were studied. Texture profile analysis showed that when heated at ambient pressure there was the expected increase in hardness with increasing temperature and when pressure was applied at room temperature there was again the expected increase in hardness with increasing pressure. Similar results to those found at ambient temperature were found when pressure was applied at 40 degrees C. However, at higher temperatures, 60 and 70 degrees C it was found that pressures of 200 MPa caused large and significant decreases in hardness. The results found for hardness were mirrored by those for gumminess and chewiness. To further understand the changes in texture observed, intact beef longissimus dorsi samples and extracted myofibrils were both subjected to differential scanning calorimetry after being subjected to the same pressure/temperature regimes. As expected collagen was reasonably inert to pressure and only at temperatures of 60-70 degrees C was it denatured/unfolded. However, myosin was relatively easily unfolded by both pressure and temperature and when pressure denatured a new and modified structure was formed of low thermal stability. Although this new structure had low thermal stability at ambient pressure it still formed in both the meat and myofibrils when pressure was applied at 60 degrees C. It seems unlikely that structurally induced changes can be a major cause of the significant loss of hardness observed when beef is treated at high temperature (60-70 degrees C) and 200 MPa and it is suggested that accelerated proteolysis under these conditions is the major cause. PMID- 22062403 TI - Species and muscle differences in L-carnitine levels in skeletal muscles based on a new simple assay. AB - We have adapted the enzymatic method [Biochemical and Biophysical Research Communications 176 (3) (1991) 1617] for the safe and rapid assay of L-carnitine (L-CA) in skeletal muscle using a microplate reader. The concentration of L-CA in fresh semitendinosus muscle from broiler chicken, pig, beef cattle, deer, horse and goat muscle were 0.69, 1.09, 1.86-3.57, 4.57, 4.95 and 11.36 MUmol/g wet weight, respectively. The animals which had higher concentration of L-CA, also had the highest amounts of myoglobin as an index to the redness of the muscle. Furthermore, we investigated this relationship between white muscle, M. pectoralis profundus, and red muscle, M. soleus, in laying hens. The L-CA and myoglobin concentration in red muscle were significantly higher than those in white muscle (p<0.01). These findings suggest that L-CA concentration in muscle is related to oxygen metabolism and to myofiber types. PMID- 22062404 TI - Tenderization of buffalo meat using plant proteases from Cucumis trigonus Roxb (Kachri) and Zingiber officinale roscoe (Ginger rhizome). AB - This study was conducted to develop a method for improving tenderness and overall qualities of tough buffalo meat using plant proteolytic enzymes from Cucumis trigonus Roxb (Kachri) and Zingiber officinale roscoe (Ginger rhizome). Their tenderizing efficacy was compared with the most popular enzyme papain. 3*3*3 cm chunks from Biceps femoris muscles of spent Murrah buffaloes (4-5 years age) were marinated with distilled water (control), 2% (w/w) powdered cucumis extract, 5% (w/v) ginger extract or 0.2% (w/w) papain for 48 h at 4 degrees C and subjected to various physico-chemical, histological and sensory evaluations. An increase (p<0.01) in collagen solubility, sarcoplasmic and myofibrillar protein solubility, and reduction (p<0.01) in shear force values were observed in all enzyme-treated samples compared to control. Electrophoretic pattern of muscle proteins also revealed extensive proteolysis and reduction in number of protein bands in all treated samples. Improvement (p<0.01) in flavor, juiciness, tenderness and overall acceptability scores were observed in all enzyme-treated samples compared to controls. Ginger extract-treated meat samples received better scores for appearance, flavor, tenderness and overall acceptability. From these results, it is shown that ginger and cucumis can be used as an effective alternative to papain. PMID- 22062405 TI - Development of optimal protocol for visible and near-infrared reflectance spectroscopic evaluation of meat quality. AB - The present experiments were conducted to develop an optimal protocol for visible and near-infrared reflectance spectroscopic evaluation of meat quality. It was determined that spectra were more repeatable using a 35 mm-diameter high intensity reflectance probe rather than a 3 mm-diameter reflectance probe. Using the high-intensity reflectance probe, spectra were generally very repeatable (e.g., repeatability at 1080 nm ranged from 0.94 to 0.99) regardless of the number (50, 40, 30, 20, or 10) of spectra averaged per observation. At each wavelength (350-2500 nm), the highest repeatability was obtained when 20 spectra were averaged. It was determined that spectra were greatly different when the length of time that the muscle was exposed to air (bloomed) before spectroscopy was increased from 2 to 60 min. However, regardless of bloom time, the repeatability of reflectance values was >0.90 at each wavelength between 462 and 1371 nm. The protocol developed in this experiment should facilitate future experiments to determine if visible and near-infrared spectroscopy can be used to accurately predict meat quality. PMID- 22062406 TI - Effect of locust bean/xanthan gum addition and replacement of pork fat with olive oil on the quality characteristics of low-fat frankfurters. AB - The effects of reducing fat level from 20% to 12% and 9%, substituting pork fat with olive oil and adding locust bean/xanthan gum (0.5% and 0.6%) on emulsion stability, jelly and fat separation, processing yield, cook loss, texture and sensory characteristics of frankfurters were investigated and compared with control samples. Addition of locust bean/xanthan gum produced a significant increase in hydration/binding properties, characterised by lower cook losses, increasing yield, better emulsion stability and lower jelly and fat separation. The substitution of pork fat by olive oil did not affect these parameters. Indeed, results showed that reducing fat levels together with increasing moisture and locust bean/xanthan gum addition do not affect the sensory or textural properties, but olive oil addition produces a decrease in hardness and an increase in adhesiveness, however the overall acceptability was not affected. PMID- 22062407 TI - Volatile compounds in Iberian dry-cured loin. AB - The volatile profile of Iberian dry-cured loin from four different Iberian pig lines (Entrepelado, Lampino, Retinto and Torbiscal) and two feeding systems (OUT fed on acorn and grass-vs.-IND - fed on high oleic acid concentrate) was studied using solid phase microextraction (SPME). 133 volatile compounds were identified and assigned to 16 chemical families. Alcohols were the major group, ethanol being the main compound. The high number of esters detected and the levels of ethanol and acetic acid found, points to an important role of microorganism activity in the formation of volatile compounds in Iberian dry-cured loin. Sulphur compounds, coming mostly from garlic, constituted an important group, with 14 compounds. Significant differences were found among loins from pigs reared in different feeding systems but not among Iberian pig lines. Dry-cured loins from OUT pigs showed higher levels of many compounds derived from lipid oxidation, such as octanoic acid (P=0.000), decanoic acid (P=0.018) or hexanal (P=0.014). PMID- 22062408 TI - Comparison of different methods for determination of drip loss and their relationships to meat quality and carcass characteristics in pigs. AB - Samples of the M. longissimus dorsi of 776 pigs from three commercial lines were used to compare two methods for measuring drip loss, referred to as the EZ DripLoss and bag methods. Furthermore, relationships between drip loss and other meat quality and carcass traits were analysed. The bag method used a slice of M. longissimus dorsi of approximately 120 g hung in an airtight container whereas the EZ-DripLoss method used two samples of approximately 10 g placed in drip loss containers. In the bag method, samples taken at 24 h post-mortem were measured 24 and 48 h after sampling and average drip loss was 1.94% and 3.33% at 24 and 48 h, respectively. Correlation between these consecutive measurements was high (r=0.98). Using the EZ-DripLoss method, drip loss of samples taken at 24 h post mortem was measured 48 h after sampling and showed an average value of 4.97%. Correlation between the drip loss obtained using EZ-DripLoss and bag methods was high (r=0.86). Relationships between drip loss and other meat quality traits were similar for both methods. Highest correlations were observed between drip loss and pH(45) (r=-0.52 and -0.48 using EZ-DripLoss method(48) and bag method(48), respectively) and the lowest to Minolta a (*) value (r=0.11 and 0.09, respectively). Correlations among several carcass traits, such as lean content, and drip loss were low or not significant. Low associations between loin eye area (cm(2)) and drip loss were obtained regardless of the method used to determine drip loss (r=0.21 and 0.18 using EZ-DripLoss method(48) and bag method(48), respectively). For routine measurements, the EZ-DripLoss method is recommended because it showed a high correlation with the bag method but is easier to perform and is more standardised. PMID- 22062409 TI - Effects of culinary treatment (desalting and boiling) on chemical and lipid composition of dry-cured pork forelegs. AB - In the northwest of Spain, dry-cured pork forelegs are eaten after a process in which they are desalted and boiled. The effects of this culinary practice on the composition (mainly in relation to the lipids) of the external and internal muscles of dry-cured forelegs were studied. The dry-cured pork forelegs after culinary treatment showed a dry matter content of 46-47%, in both internal and external muscles. The culinary treatment caused decrease of ash, NaCl and cholesterol contents and increase of lipid and protein contents. Nitrates and nitrites decreased only in external muscles. No significant changes were observed in the TBA values. The culinary treatment caused significant decreases in phospholipids and significant increases in free fatty acids. The free fatty acids of boiled desalted dry-cured forelegs showed higher PUFA proportions than dry cured forelegs, mainly in external muscles. PMID- 22062410 TI - Interactions between meat proteins and barley (Hordeum spp.) beta-glucan within a reduced-fat breakfast sausage system. AB - Barley beta-glucan, a soluble fibre component with health benefits, has the potential to be used as a fat replacer in meat systems. Interactions between meat proteins and beta-glucan gum were examined in reduced-fat (12%, w/w) sausages formulated with beta-glucan at 0.3% (w/w) (0.3beta-gl) and 0.8% (w/w) (0.8beta gl) levels, as well as high- and reduced-fat controls. Cooking loss results indicated that beta-glucan gum held more water in cooked sausages than control gum (carboxymethyl cellulose), due to its ability to form a tighter network within the protein matrix, as shown by scanning electron microscopy. In a raw system, beta-glucan gum was not as effective at retaining moisture as a stable protein network, formed by heating. Differential scanning calorimetry results showed that sausages with a higher gum to protein ratio required additional energy for protein denaturation to occur. Findings indicate that beta-glucan gum increases the amount of moisture held in a cooked meat protein system, due to the physical entrapment of water, when compared to the high-fat control, but is similar to the reduced-fat formulation with added water. PMID- 22062411 TI - Detection of meat species using TaqMan real-time PCR assays. AB - Species-specific real-time PCR (TaqMan) assays were developed for detection of beef, pork, lamb, chicken and turkey. Assays were developed around small (amplicons <150 base pairs) regions of the mitochondrial cytochrome b (cytb) gene. Speciation was achieved using species-specific primers. For detection purposes, two TaqMan probes were developed; the first was specific to the mammalian species (beef, lamb and pork), the second to the poultry species (chicken and turkey). Normal end-point TaqMan PCR conditions were applied; however, PCR was limited to 30 cycles. Applying the assays to DNA extracts from raw meat admixtures, it was possible to detect each species when spiked in any other species at a 0.5% level. The absolute level of detection, for each species, was not determined; however, experimentally determined limits for beef, lamb and turkey were below 0.1%. PMID- 22062412 TI - Effect of Debaryomyces spp. on aroma formation and sensory quality of dry fermented sausages. AB - The effect of Debaryomyces spp. used in combination with starter cultures (lactic acid bacteria and staphylococci) was studied in the development of dry-fermented sausage aroma and final sensory quality. Volatile compounds were extracted by solid-phase micro extraction and analysed by gas chromatography-mass spectrometry. A paired comparison test was done to determine which sausage was preferred. Debaryomyces spp. showed an important effect on volatile generation during ripening by inhibiting the generation of lipid oxidation products and promoting the generation of ethyl esters that contribute to proper sausage aroma. However, the amount of Debaryomyces spp. used is important because larger amounts produced high generation of acids that mask the positive effect. PMID- 22062413 TI - Cleavage of desmin by cysteine proteases: Calpains and cathepsin B. AB - The intermediate filament protein, desmin, was purified from pork longissimus dorsi and incubated with either MU-calpain, m-calpain or cathepsin B. Proteolysis of desmin was followed using SDS-PAGE and Western blotting. After incubation of desmin with the proteases, cleavage sites on the desmin molecule were identified by N-terminal sequencing of the different proteolytic fragments. Desmin incubated with either m-calpain or MU-calpain was primarily cleaved in the head and tail region leaving the rod domain relatively intact even after prolonged incubation. Incubation with cathepsin B produces a sequential C-terminal degradation pattern characteristic of this dipeptylpeptidase. The substrate primary structure was not found to be essential for regulation of the proteolytic activity of the cysteine peptidases studied. However, the degradation patterns obtained imply that calpains are involved in degradation of desmin early post-mortem, targeting the non-helical region of the desmin molecule and resulting in depolymerisation and initial disorganisation of the intermediate filament structures of the muscle cell. PMID- 22062414 TI - Effect of muscle source on premature browning in ground beef. AB - Premature browning (PMB) describes cooked beef that may appear done before reaching 71 degrees C. Ground beef from paired Longissimus lumborum (LL) and Psoas major (PM) muscles was formed into patties. Patties were cooked immediately, and after 48 and 96 h storage at 4 degrees C. Total reducing activity (TRA) and external color were measured immediately prior to cooking. Patties were cooked to internal end point temperatures of 60, 66, 71 or 77 degrees C and internal cooked color (L(*), a(*) and b(*) values) was measured. Raw PM patties had greater L(*) values and lesser a(*) values than those from LL (P<0.05). For LL and PM, raw a(*) and b(*) values decreased with storage from 0 h to 96 h (P<0.05). At 0 and 48 h storage, cooked patties prepared from PM had greater a(*) values than those prepared from LL at all internal endpoint temperatures (P<0.05). Internal cooked a(*) values of patties from PM decreased with storage of raw patties, whereas it was stable for LL patties (P<0.05). PMID- 22062415 TI - Comparison of electrolyzed oxidizing water with other antimicrobial interventions to reduce pathogens on fresh pork. AB - To date, the effectiveness of electrolyzed oxidizing (EO) water against bacteria associated with fresh pork has not been determined. Using a hand-held, food-grade garden sprayer, distilled water (W), chlorinated water (CL; 25 ppm), 2% lactic acid (LA), acidic EO water (EOA), or "aged" acidic EO water (AEOA; stored at 4 degrees C for 24 h) was sprayed (15 s) onto pork bellies inoculated with feces containing Listeria monocytogenes (LM), Salmonella typhimurium (ST), and Campylobacter coli (CC). Remaining bacterial populations were determined immediately following treatment, after 2 days of aerobic storage, and again after 5 days of vacuum-packaged, refrigerated storage (day 7). While LA and EOA significantly reduced (p<0.05) populations of CC at days 0 and 7, there was no significant difference (p>0.05) between antimicrobial treatments when applied to pork inoculated with ST or LM. This study demonstrates that a 15-s spray with EOA has the ability to reduce CC associated with fresh pork surfaces. However, longer contact times may be necessary to reduce other microbial contaminants. PMID- 22062416 TI - The effect of exercise stress, adrenaline injection and electrical stimulation on changes in quality attributes and proteins in Semimembranosus muscle of lamb. AB - Exercise pre-slaughter has previously been shown to increase drip loss and tenderness in the longissimus muscle of lambs. The mechanism causing higher water loss in post-mortem muscle of lambs is not well understood. This experiment examines the effects of exercise stress, adrenaline injection and electrical stimulation (ES) on meat tenderness and water holding capacity. Forty crossbred lambs (20+/-2 kg live weight) were used in this study. Meat quality measurements were carried out on the Semimembranosus muscle (SM). The ultimate pH was higher with exercise stress (pH 5.93) compared to controls (pH 5.55; P<0.01). As expected the glycogen levels 30 min and 24 h post-mortem in the exercise stressed (P<0.01) muscle were lower. Lactate concentration at 30 min post-mortem in the electrical stimulation (ES: P<0.05) treated muscle was higher than all other treatment combinations. Myofibrillar protein denaturation, measured by protein solubility, was higher (P<0.05) and the rate of proteolysis of muscle proteins titin and troponin-T, as observed with western blots, increased with exercise stress. However, there were no treatment effects on Warner-Braztler shear force (WBSF). Exercise stress and an interaction with adrenaline caused increased drip loss (P<0.05) and purge (P<0.01) from the muscle. Muscle drip from the exercise stress treatment group had lower Mg(2+) (P<0.01) and K(+) (P<0.01) than controls. The main findings were that exercise stress pre-slaughter increased water loss and the rate of titin breakdown but had no effect on tenderness measured by WBSF. Together the different rates of proteolysis, protein denaturation and ionic conditions may have caused the reduced capacity of the muscle proteins to hold water, despite their relatively high ultimate pH. PMID- 22062417 TI - Oxidative stability of chilled pork chops following long term freeze storage. AB - Colour stability and development of lipid oxidation were followed during chill storage for 6 days of chops from M. Longissimus dorsi produced from pigs with high (6.3) and low (5.5) ultimate pH (pH(u)). The chops from the same individual pigs were either chill stored at 2 days post-mortem or after frozen storage for 30 months (pre-frozen). Initial redness, measured as tristimulus parameter a(*), was lower for pre-frozen chops than for fresh chops. Chops with the high pH(u) had a stable a(*)-value during chill storage, while chops with the low pH(u) showed a rapidly decreasing a(*)-value both for fresh and pre-frozen chops. In contrast, initial lipid oxidation, measured as TBARS, was similar for pre-frozen and fresh chops prior to chill storage for both the high and the low pH(u) meat but developed most significantly in pre-frozen, low pH(u) meat. Individual differences in colour stability and development of lipid oxidation between pigs were notable for pre-frozen low pH(u) meat and need to be considered in quality control since meat from single pigs otherwise might give problems. PMID- 22062418 TI - The antioxidative activity of plant extracts in cooked pork patties as evaluated by descriptive sensory profiling and chemical analysis. AB - Antioxidative efficiency of extracts of rosemary, green tea, coffee and grape skin in precooked pork patties was investigated during storage under retail conditions (10 days, 4 degrees C, atmospheric air), using descriptive sensory profiling following reheating and quantitative measurements of hexanal, thiobarbituric acid reactive substances (TBARS) and vitamin E as indicators of lipid oxidation. The initial oxidative status of pork patties (evaluated by ANOVA) showed a significant lower level of secondary oxidation products and higher levels of vitamin E in patties with extracts incorporated, indicating that the extracts retarded lipid oxidation during processing of the meat. Data analysis for the storage study was based on qualitative overview of sensory/chemical variation by principal component analysis (PCA) and quantitative ANOVA-PLSR for determination of the relationship between design variables (days of chill-storage, extract treatment) versus sensory-chemical variables and PLSR for elucidating the predictive ability of the chemical methods for sensory terms. Lipid oxidation was seen to involve a decrease in perception of meat flavour/odour and a concomitant increase in the off-flavour/odours linseed, rancid. TBARS, hexanal and vitamin E were all significant predictive indices (P<0.05) for the majority of the sensory terms, while vitamin E through negative correlation with TBARS and hexanal displayed its antioxidative effect and thus, its ability to preserve sensory fresh meat flavour/odour. The effect of the various extracts incorporated in the product was clearly related to the degree of lipid oxidation and an overall ranking of the antioxidative efficiency of extracts in declining order became apparent: Rosemary>Grape skin>Tea>Coffee>Reference. Furthermore, the relation between extracts and vitamin E indicated that the extracts, to some extent, interacted with the vitamin and prevented it from degrading. In conclusion, the rosemary extract displayed potential for maintaining sensory eating quality in processed pork products. PMID- 22062419 TI - Effects of muscle shortening and proteolysis on Warner-Bratzler shear force in beef longissimus and semitendinosus. AB - Interactions between muscle shortening and proteolysis and their effects on Warner-Bratzler (WB) shear force were investigated in beef m. longissimus (LD) and m. semitendinosus (ST). Muscles were taken within 30 post-mortem from eight Hanwoo steers, divided into three portions, and incubated at 5, 15, or 36 degrees C for 24 h, during which time rigor mortis developed. ST at 36 degrees C had a significantly (P<0.05) lower pH at 3 h than LD incubated at the same temperature. However, pH values became similar after 3 h. Both muscles at 5 and 15 degrees C had almost similar pH during rigor development, with significantly (P<0.05) lower pH for ST. Sarcomere length and WB-shear force did not differ significantly between muscles incubated at the same temperature. For both muscles at 5, 15, and 36 degrees C, sarcomere length was 1.52, 1.76 and 1.44 MUm, and WB shear force was 93.2, 55.9 and 45.1 N. The rates of MU-calpain autolysis and Troponin-T degradation were in the order of 36 degrees C>15 degrees C?5 degrees C, with a tendency for ST to have a slightly faster rate than LD muscle. Thus, the effect of sarcomere length on shear force may depend on the extent of proteolysis and the potential of endogenous proteolysis may supersede toughness caused by short sarcomeres. The toughness of cold shortened meat may depend more on endogenous enzymatic tenderization than shortened sarcomere length per se. PMID- 22062420 TI - Saturation with cholesterol increases vertical order and smoothes the surface of the phosphatidylcholine bilayer: a molecular simulation study. AB - Molecular dynamics (MD) simulations of a mono-cis-unsaturated 1-palmitoyl-2 oleoyl-phosphatidylcholine (POPC) bilayer and a POPC bilayer containing 50mol% cholesterol (POPC-Chol50) were carried out for 200ns to compare the spatial organizations of the pure POPC bilayer and the POPC bilayer saturated with Chol. The results presented here indicate that saturation with Chol significantly narrows the distribution of vertical positions of the center-of-mass of POPC molecules and POPC atoms in the bilayer. In the POPC-Chol50 bilayer, the same moieties of the lipid molecules are better aligned at a given bilayer depth, forming the following clearly separated membrane regions: the polar headgroup, the rigid core consisting of steroid rings and upper fragments of the acyl chains, and the fluid hydrocarbon core consisting of Chol chains and the lower fragments of POPC chains. The membrane surface of the POPC-Chol50 bilayer is smooth. The results have biological significance because the POPC-Chol50 bilayer models the bulk phospholipid portion of the fiber-cell membrane in the eye lens. It is hypothesized that in the eye lens cholesterol-induced smoothing of the membrane surface decreases light-scattering and helps to maintain lens transparency. PMID- 22062422 TI - Addition of synthetic and natural antioxidants to alpha-tocopheryl acetate supplemented beef patties: effects of antioxidants and packaging on lipid oxidation. AB - Friesian steers (n=5), aged 26-27 months, were fed a diet containing 2000 (supplemented) IU alpha-tocopheryl acetate/head/day for approximately 50 days prior to slaughter. Muscularis semimembranosus muscles from supplemented cattle were held in frozen storage (-20 degrees C*12 weeks) following which they were minced and divided into five batches. The batches contained: (1) control, containing only vitamin E supplemented beef (C); (2) vitamin E supplemented beef with 4% soya oil (S); (3) vitamin E supplemented beef mixed with 0.2% Duralox NMC dissolved in 4% soya oil (R1); (4) vitamin E supplemented beef mixed with 0.25% Herbalox type 25 (containing 25 natural antioxidant extracts of rosemary) dissolved in 4% soya oil (R2); and (5) vitamin E supplemented beef mixed with a 1:1 mixture of 0.01% (w/w) BHA and 0.01% (w/w) BHT dissolved in 4% soya oil (B). The meat was then aerobically packaged (A) or packaged under the following modified atmospheres (MAP); 30:70 (M(1)); 70:30 (M(2)) or 80:20 (M(3)) (O(2):CO(2)). Oxidative stability (TBARS) and Hunter 'a' values (redness) were determined in all beef patties over 8 days of refrigerated (4 degrees C) storage. Under MAP or aerobic packaging conditions, elevated oxygen levels brought about increased (P<0.05) TBARS numbers during refrigerated storage. However, the addition of rosemary extracts or BHA/BHT significantly (P<0.05) improved the oxidative stability of dietary alpha-tocopheryl acetate supplemented beef. Rosemary extracts were as effective in reducing TBARS as the combination of synthetic antioxidants, BHA/BHT. PMID- 22062421 TI - The role of VDAC in cell death: friend or foe? AB - As the voltage-dependent anion channel (VDAC) forms the interface between mitochondria and the cytosol, its importance in metabolism is well understood. However, research on VDAC's role in cell death is a rapidly growing field, unfortunately with much confusing and contradictory results. The fact that VDAC plays a role in outer mitochondrial membrane permeabilization is undeniable, however, the mechanisms behind this remain very poorly understood. In this review, we will summarize the studies that show evidence of VDAC playing a role in cell death. To begin, we will discuss the evidence for and against VDAC's involvement in mitochondrial permeability transition (MPT) and attempt to clarify that VDAC is not an essential component of the MPT pore (MPTP). Next, we will evaluate the remaining literature on VDAC in cell death which can be divided into three models: proapoptotic agents escaping through VDAC, VDAC homo- or hetero oligomerization, or VDAC closure resulting in outer mitochondrial membrane permeabilization through an unknown pathway. We will then discuss the growing list of modulators of VDAC activity that have been associated with induction/protection against cell death. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism. PMID- 22062423 TI - Occurrence of Escherichia coli O157:H7, Listeria monocytogenes, Salmonella and Campylobacter spp. on beef carcasses in Northern Ireland. AB - A survey of beef carcasses was conducted in all 10 European community approved abattoirs in Northern Ireland to determine the incidence of Escherichia coli O157:H7. Analyses were based on excised samples of neck meat taken less than 48 h post-kill. Overall, 780 carcasses were sampled and all were negative for E. coli O157:H7. A sub-set of samples was analysed for the presence of Listeria monocytogenes (n=200), Salmonella (n=200) and Campylobacter spp.(n=100). L. monocytogenes was not detected but Listeria innocua was found on five carcasses and Listeria seeligeri on one. Three carcasses carried salmonellas; Salmonella Mbandaka was found on two and Salmonella Thompson on one. Campylobacter spp. were not detected on any carcasses. The results indicate that very few beef carcasses in Northern Ireland appear to carry any of the four pathogens sought, and this may help explain the low incidence of E. coli O157:H7 in the Northern Ireland human population, relative to the rest of the UK. PMID- 22062424 TI - Effect of pre-slaughter physiological conditions on the oxidative stability of colour and lipid during chill storage of pork. AB - The physiological condition of the live animal was found to significantly affect colour, lipid oxidation and water holding capacity of chill stored pork chops (M. Longissimus dorsi) in a study, where various pre-slaughter conditions were achieved by the following four treatments: (A) control; (B) subjected to treadmill exercise immediately prior to stunning; (C) given epinephrine injection 15 h prior to slaughter; and (D) given epinephrine injection 15 h before slaughter and further subjected to treadmill exercise immediately before stunning. The treatments resulted in variations in energy metabolites (glycogen, lactate, creatine phosphate, ATP) and ultimate pH (pH(u)), with the lowest pH(u) in chops from treatments A and B, and in significantly different tristimulus colour L(*)-, a(*)- and b(*)-parameters, although the effect of treatment on colour was not consistent during the chill storage period of 6 days. Overall, chops from treatments A and B had significantly higher L(*)- and b(*)-values (were paler and less blue) than chops from C and D during storage under conditions typical for retail trade. The initial a(*)-values were higher (redder) in chops from treatments A and B, but the colour, as judged by the a(*)-values, was less stable in meat from these treatments compared with treatments C and D. Lipid oxidation, evaluated by thiobarbituric acid reactive substances (TBARS) in the fresh meat, and drip loss, measured after 6 days of storage, were both significantly higher in chops from treatments A and B compared to chops obtained from treatments C and D. Statistical analysis relating the pH and the level of various energy metabolites post-mortem in the individual animals to the measured quality parameters, revealed that pH(u) was the most important factor affecting product quality. In conclusion, over all product quality depends on obtaining a pH(u) in the narrow range where both meat quality parameters such as colour, lipid oxidation and drip loss as well as microbiological aspects have to be considered. PMID- 22062425 TI - Productivity and carcass characteristics of pure and crossbred Chinese Yellow Cattle. AB - The carcass characteristics of 334 Chinese Yellow Cattle, and their Simmental and Limousin crosses, were investigated in abattoirs in Hebei and Sandong provinces of China. The overall slaughter age was 4.8+/-2.2 years at a mean liveweight of 527.28+/-77.0 kg. Mean ages and liveweights for Yellow Cattle and its crosses were, respectively, 5.29+/-2.03 and 2.85+/-1.71 years and 519.43+/-78.7 and 563.13+/-56.8 kg. Carcass weights varied considerably and, consequently, so did subcutaneous fat depths and dressing percentages. Overall, mean carcass weights, subcutaneous fat depths and, dressing percentages and eyemuscle areas were 283.9+/-64.1 kg, 14.0+/-8.0 mm, 54.0+/-4.0%, and 62.7 +/-13.3 cm(2), respectively. Compared with pure Yellow Cattle, the crosses were slaughtered at younger age, and had larger live and carcass weights, higher dressing percentages, less subcutaneous fat depth and bigger eyemuscle areas. It is concluded that crossbreeding can significantly improve Yellow Cattle' meat productivity, however feeding systems need to be improved and an appropriate grading system developed to improve beef production and quality in China. PMID- 22062426 TI - Post-mortem evolution of non-protein nitrogen and its peptide composition in growing lamb muscles. AB - Twenty-two 4-month-old lambs were used in two experiments to assess the effects of growth rate, induced by different feeding levels, and ageing (21 days, 4 degrees C) on non-protein nitrogen (NPN) contents and their peptide composition. Muscle (Longissimus dorsi, Semimembranosus) and sex (male, female) effects were also studied. During ageing, NPN contents increased (15-20%). This variation represented 1.6-2.8% of total nitrogen. Peptides extracted from fresh muscles were in the range of molecular weight (MW) up to 12 kDa, the majority being less than 2.4 kDa (45-48%). During ageing, peptide average MW decreased (11.5-27.6%). High growth rate increased NPN contents at slaughter (+6-14%) and during ageing. Peptide average MW and post-mortem proteolysis rate as with to NPN variations were also higher. Differences between sex were observed at the end of the ageing period. Muscle effects were observed on the peptide class from 6.8 to 3.4 kDa. PMID- 22062427 TI - Use of calcium lactate with salt-phosphate and alginate-calcium gels in restructured pork rolls. AB - The study was carried out to evaluate restructured pork rolls (RPR) prepared by using salt-phosphate and alginate-calcium gels with or without calcium lactate. Five types of RPR were prepared with: (1) 1.75% sodium chloride+0.3 phosphate (SP); (2) 1.75% sodium chloride+0.3% phosphate+0.3% calcium lactate (SPL); (3) 0.7% sodium alginate+0.125% calcium carbonate (AC); (4) 0.7% sodium alginate+0.3% calcium lactate (AL); and (5) 0.7% sodium alginate+0.125% calcium carbonate+0.3% calcium lactate (ACL). Cooking yield and cooked binding strength were significantly (P<0.05) higher in RPR containing salt and phosphate whereas pH and raw binding strength were significantly (P<0.05) higher in RPR containing alginate and calcium. Texture profile analysis indicated significantly (P<0.05) higher firmness and cohesiveness in RPR containing SPL and ACL. Sensory scores were significantly (P<0.05) higher in SP, SPL and ACL than AC and AL treatments. Results of storage studies indicated significant (P<0.05) increases in pH, TBARS numbers, metmyoglobin and microbial counts with storage in all the treatments. The results suggest that quality characteristics of raw product were better when RPR were prepared with alginate-calcium whereas quality characteristics of cooked product were better when rolls were prepared with salt-phosphate. Further, addition of calcium lactate improved sensory characteristics and shelf life of both alginate-calcium and salt-phosphate restructured pork rolls. PMID- 22062428 TI - Carcass traits, muscle characteristics, and palatability attributes of lambs expressing the callipyge phenotype. AB - Dorset*Suffolk crossbred wethers expressing a normal phenotype (normal, n=10) and callipyge phenotype (CLPG, n=9) were fed individually and slaughtered upon reaching maximum growth potential. Carcass weight did not differ (P>0.05), but fat thickness was lower (0.30 vs. 0.56 cm), ribeye area was greater (24.4 vs. 16.6 cm(2)), and USDA yield grade was improved (1.6 vs. 2.6) for CLPG carcasses (P < 0.05). Carcasses from CLPG demonstrated higher cutability and a more desirable muscle to bone ratio, with less fat and more lean as a percentage of total side weight (P<0.05). Biceps femoris (BF), semitendinosus (ST), semimembranosus (SM), longissimus thoracis et lumborum (LTL), and triceps brachii (TB) were used to compare muscle characteristics of both phenotypes. Muscle from normal lambs had lower calpastatin activity, higher fat percentages and lower moisture percentages (P<0.05). Total amount and solubility of collagen were not affected by phenotype nor was sarcomere length. Shear force and trained sensory attributes were evaluated for BF and LTL only. Shear force values did not differ between normal and CLPG BF while CLPG LTL had higher (P< 0.05) shear force values than normal LTL. Biceps femoris did not differ between phenotypes in trained sensory panel ratings. However, CLPG LTL received the lowest sensory ratings for connective tissue amount and myofibrillar and overall tenderness (6.11, 4.97, and 4.95, respectively) and the normal LTL received the highest ratings (P < 0.05; 7.10, 7.00, and 6.90, respectively). The CLPG phenotype had a positive influence on carcass characteristics but had a negative influence on tenderness of some muscles, possibly through the myofibrillar component of the muscle. PMID- 22062429 TI - Effect of dietary alpha-tocopherol supplementation on color and lipid stability in pork. AB - Myoglobin and lipid oxidation are major causes of quality deterioration in fresh pork. A process to enhance color and lipid stability would prove valuable to the pork industry given the current trend of centralized packaging and distribution to retail markets. Our objective was to determine the effects of dietary alpha tocopherol (alpha-Toc) supplementation on color and lipid stability in ground pork, and loin chops stored in modified atmosphere packaging (MAP). Yorkshire crossbred pigs (n=20) were randomized into two groups and fed diets containing 48 (CON) or 170 mg alpha-Toc acetate/kg feed (VIT-E) for 6 weeks before slaughter. Plasma alpha-Toc concentration was measured weekly. Post-slaughter, Boston butt shoulders were ground, formed into patties with or without 1.5% salt, and stored fresh at 4 degrees C for 0, 2, 4, or 6 days, and frozen at -20 degrees C for 45 or 90 days. Pork loin chops were packaged aerobically and stored at 4 degrees C for 0, 2, 4 or 6 days, or in MAP at 4 degrees C for 7, 10 or 13 days prior to Hunter L*,a*,b* and TBARS analyses. alpha-Toc concentration of longissimus dorsi, psoas major, biceps femoris, semimembranosus and semitendinosus muscles was determined. Plasma alpha-Toc was greater (P<0.05) in VIT-E animals compared with CON and alpha-Toc concentrations were greater (P<0.05) in all VIT-E muscles compared with CON. TBARS values of both fresh and salted patties were less in VIT E than in CON meat following 6 days at 4 degrees C; VIT-E TBARS of salted patties were less (P<0.05) after 45 days at -20 degrees C compared with CON. alpha-Toc supplementation did not influence (P>0.05) color of aerobically packaged or MAP chops, or of fresh or salted pork patties. alpha-Toc supplementation reduced TBARS formation in fresh and salted pork but had no significant impact on color. PMID- 22062430 TI - Analysis of visible reflectance spectra of stored, cooked and diseased chicken meats. AB - Visible spectra of cold stored, cooked, and diseased chicken meats were collected. Changes in ratios of R(1)=A(485 nm)/A(560 nm) and R(2)=A(635 nm)/A(560 nm,) which are related to absorbances of the bands at 485 (metmyoglobin), 560 (oxymyoglobin), and 635 nm (sulfmyoglobin), were observed to be useful for studying the variation of meat color under the conditions of cold storage and cooking process. Such a strategy was also applied to classify fresh-raw wholesome and unwholesome meats into respective classes, and the result was compared with that produced from a chemometric model. The strategy might be used as a simple methodology for monitoring the color variation of meats where the development of the chemometric model is either impractical or not desirable. PMID- 22062431 TI - Effects of dietary vitamin E supplementation and packaging on the colour stability of sliced pasteurized beef ham. AB - The effect of supplementation of vitamin E (2025 IU animal(-1) day(-1)) in the diet of beef bulls on the colour stability of pasteurized beef ham was studied. Control and enriched diets were provided for the last 136 days before slaughter. Pasteurized hams were manufactured from Mm. semitendinosus from eight animals per dietary group. Half of the samples of sliced ham from control (CON) and supplemented (SUP) bulls were packaged under vacuum (VAC) and half in low-oxygen modified atmosphere packs (FOG, gas mixture: CO(2)/N(2)=50/50). The packages were kept under constant illumination for 28 days at 8 degrees C. During storage, the number of colony-forming units (CFU) reached a maximum of 5x10(7) g(-1). The microflora was dominated by lactic acid bacteria. The supplementation with vitamin E showed no effect on microbial growth. Lipid oxidation was stable during storage. A significant difference between both dietary groups was detected for the decrease in the redness values during storage. Redness values of CON vacuum packaged samples decreased (P < 0.01) with time, whereas those for the SUP products only tended to decrease. The redness values of FOG-packed ham were higher than those of VAC-packed ham at the end of the display period, irrespective of the dietary group. Overall, colour appeared to be more stable in the FOG-packed products than in the VAC-packed products. It can be concluded that dietary supplementation of bulls with vitamin E appears to offer only a minor improvement in colour stability over current feeding regimens when the Mm. semitendinosus are used to make cured, pasteurized ham-type products. PMID- 22062432 TI - Effect of substituting pork backfat with rind on quality characteristics of pork sausage. AB - A study was conducted in which pork backfat in pork sausage was replaced with rind at 0, 33, 66 and 100% levels. The high moisture and high protein content of rind consequently influenced the moisture and protein content of the final products. The fat level decreased with increase in the level of rind in the sausage. The lowest fat content of 7.99% was recorded on batch 4 sausage with 100% rind replacement level. Replacement of pork backfat with rind decreased refrigeration and cooking weight losses. The values obtained for sensory properties decreased with increase in the level of rind in the sausage. Up to 66% pork backfat can be replaced with rind in pork sausage without adverse effect on processing yield. PMID- 22062433 TI - Influence of weak organic acids and salts on the denaturation characteristics of intramuscular connective tissue. A differential scanning calorimetry study. AB - Intramuscular connective tissue obtained from Longissimus dorsi muscle of a 4 year-old beef carcass was treated with NaCl solutions of 2, 4, and 6% (w/v), and CaCl(2) solutions of 50, 100, and 150 mM, and citric and lactic acid solutions of 0.5, 1.0, and 1.5% for three different marinating periods (24, 46, and 72 h). Changes in denaturation characteristics were investigated using differential scanning calorimetry and it was found that the denaturation onset temperature (T(o)) and the denaturation peak temperature (T(p)) increased as the NaCl concentration increased but decreased as the CaCl(2) concentration increased, irrespective of marinating time. Lactic and citric acid decreased T(o) to about 39 degrees C, from over 60 degrees C breaking the structure of fibrils. PMID- 22062434 TI - The effects of ascorbic acid, taurine, carnosine and rosemary powder on colour and lipid stability of beef patties packaged in modified atmosphere. AB - This research was aimed at evaluating the inhibition of oxidative changes of beef patties packaged in modified atmosphere (70% O(2)+20% CO(2)+10% N(2)) by natural antioxidants: ascorbic acid (500 ppm), taurine (50 mM), carnosine (50 mM), rosemary powder (1000 ppm) and their combinations with the first. Beef patties stored at 2+/-1 degrees C for 20 days were evaluated for colour (L*, a*, b*, C* and H*), TBARS, metmyoglobin formation (% of total myoglobin), psychrotrophic microbial counts and sensory odour and discolouration. Rosemary, either alone or with ascorbic acid, was highly effective in inhibiting both metmyoglobin formation and lipid oxidation; sensory analysis was in agreement with these results. Ascorbic acid, ascorbic acid+taurine and ascorbic acid+carnosine treatments showed a limited inhibitory effect of myoglobin oxidation, while carnosine and carnosine+ascorbic acid were effective in inhibiting lipid oxidation. Taurine alone failed to exert any antioxidant effect. Principal components analysis confirmed these results. PMID- 22062435 TI - Cholesterol oxidation products in irradiated raw meat with different packaging and storage time. AB - The effect of irradiation and packaging conditions on the formation of cholesterol oxidation products (COPs) as well as lipid oxidation products was determined in raw turkey leg, beef, and pork loin meat during 7 days of storage. Ground turkey leg, beef, and pork loin muscles were prepared as patties. The patties were individually packaged either in oxygen-permeable or impermeable bags, irradiated at 0 or 4.5 kGy using a Linear Accelerator, and stored at 4 degrees C. The COPs such as 7alpha-hydroxycholesterol, 7beta-hydroxycholesterol, and 7-ketocholesterol were detected in fresh raw meats at 0 day at the level of 10.9 to 49.2 MUg/g lipid. After 7 days of storage, other COPs such as epoxides, 20alpha-hyroxycholesterol, and choletanetriol were formed in mainly aerobically packaged and irradiated raw meats. Packaging effect was more crucial on the cholesterol and lipid oxidation than irradiation. In aerobically packaged and irradiated meats, turkey leg muscles had higher COPs value than beef or pork did. COPs and thiobarbituric acid reactive substances (TBARS) values had a strongly positive correlation in turkey leg and pork. But, cholesterol oxidation in beef proceeded in irradiated and aerobically stored samples despite of its low level of TBARS value. PMID- 22062437 TI - Theories and mechanisms of aging. AB - This article discusses various theories of aging and their relative plausibility related to the human aging process. Structural and physiologic changes of aging are discussed in detail by organ system. Each of the organ systems is discussed when applicable to the various theories of aging. Normal versus abnormal aging is discussed in the context of specific aging processes, with atypical presentations of disease and general links to life expectancy. Life expectancy and lifespan are discussed in the context of advances in medical science and the potential ultimate link to human life span. PMID- 22062438 TI - State of the art in anti-aging trends. AB - This chapter is an effort to provide a cursory overview of current paradigms in the realm of anti-aging medicine. This subject will be evaluated according to current philosophic, clinical and scientific perspectives which are predominant in the field at this time. PMID- 22062439 TI - Aging and disease prevention. AB - This article reviews evidence-based recommendations for geriatric prevention disciplines and topics including health behaviors (e.g., smoking cessation, physical activity), metabolic disorders, cardiovascular diseases, cancers, immunizations, depression, the promotion of independence,and polypharmacy. Recommendations for both the one-on-one, clinic-based setting and for community wide initiatives are covered for each topic, as appropriate. PMID- 22062440 TI - Hormone replacement therapy in the geriatric patient: current state of the evidence and questions for the future. Estrogen, progesterone, testosterone, and thyroid hormone augmentation in geriatric clinical practice: part 1. AB - This article presents an up-to-date review of the literature on hormone augmentation in the elderly to help primary care physicians better evaluate and utilize hormone replacement and optimization strategies to benefit their patients. The scientific literature suggests that hormone supplementation with estrogen, progesterone, testosterone, growth hormone, and thyroid hormone has the potential to improve quality of life and to prevent, or reverse, the many symptoms and conditions associated with aging, including fatigue, depression, weight gain,frailty, osteoporosis, loss of libido, and heart disease. Possible long-term side effects are also considered. PMID- 22062441 TI - Hormone replacement therapy in the geriatric patient: current state of the evidence and questions for the future--estrogen, progesterone, testosterone, and thyroid hormone augmentation in geriatric clinical practice: part 2. AB - The data reviewed herein show that hormone replacement therapies improve some conditions associated with aging. Additionally, some of the long-held fears of significant side effects associated with hormone supplementation may be overstated, especially when providing patients with individualized care and optimal monitoring. We encourage clinicians to consider such interventions based on the evidence presented.More long-term studies are needed to further quantify and substantiate the risks and benefits associated with the use of such therapies. PMID- 22062442 TI - Diets for successful aging. AB - The effects of different dietary patterns on specific age-related illness and overall longevity are discussed. PMID- 22062443 TI - Aging and the effects of vitamins and supplements. AB - Vitamin supplements are commonly consumed by elderly patients. This article reviews the evidence behind vitamin supplementation in preventing disease states common in older age, with an emphasis on randomized controlled trials. In addition to vitamins, some commonly used supplements, such as ginkgo, DHEA, and omega-3 fatty acids, are also discussed. PMID- 22062444 TI - Aging and toxins. AB - This article addresses physiologic organ system and cellular mechanisms of common toxic exposure in the elderly population. Air pollution, tobacco, alcohol, heat, cold, water pollution, medications, herbals,radiation, and other chemicals are discussed. PMID- 22062445 TI - The aging brain and neurodegenerative diseases. AB - This article reviews the current thoughts on the effects of aging on the brain. Mechanisms of neurodegeneration are discussed, particularly those associated with Alzheimer's and Parkinson's diseases. Strategies of early detection of presymptomatic disease and potential future treatments are explored. Modification of risk factors and lifestyles for disease prevention is discussed. PMID- 22062446 TI - Psychosocial factors in aging. AB - Many psychosocial factors have been associated with successful aging. The impact of social relationships, personality factors, self-perceptions,and religiosity/spirituality is reviewed in this article and recommendations for enhancing psychological aging are provided. PMID- 22062447 TI - Aging and exercise. AB - In older adults, regular exercise provides numerous health benefits that include improvements in blood pressure, coronary artery disease,diabetes, lipid profile, osteoarthritis, osteoporosis, mood,neurocognitive function, and overall morbidity and mortality. This article discusses the benefits of exercise in the elderly and how physicians can help such patients overcome barriers to exercise (eg,sedentary lifestyle, lack of education, coexisting morbidities), and offers some practical exercise prescriptions for both healthy and compromised elderly patients. PMID- 22062448 TI - Fatigue and chronic fatigue in the elderly: definitions, diagnoses, and treatments. AB - Because fatigue is so prevalent in the elderly population, it is important that physicians be well versed in the evaluation and management of this complaint. This article discusses the clinical manifestations and predisposing factors for the three major categories of fatigue: recent, prolonged, and chronic. The CDC classification of chronic fatigue syndrome is included. Patient dissatisfaction with the care for their fatigue is a common problem. Several pharmaceutical treatment methods are presented. Non-pharmacologic options, such as use of vitamins, exercise, behavior modification,and diet are also discussed. PMID- 22062449 TI - Toward a comprehensive differential diagnosis and clinical approach to fatigue in the elderly. AB - This article provides primary care physicians with an encompassing approach to fatigue to help generate a comprehensive differential diagnosis. Two-thirds of patients with fatigue will have an identifiable cause that can be elucidated with a careful history and appropriate laboratory tests. Accordingly, a wide range of differential diagnoses is presented. PMID- 22062450 TI - The rapidly changing field of "aging optimization medicine.". PMID- 22062451 TI - The human brain in 1700 pieces: design and development of a three-dimensional, interactive and reference atlas. AB - As the human brain is the most complex living organ, constructing its detailed model with exploration capabilities in a form of an atlas is a challenge. Our overall goal is to construct an advanced, detailed, parcellated, labeled, accurate, interactive, three-dimensional (3D), and scalable whole human brain atlas of structure, vasculature, tracts and systems. The objectives of this work are three-fold; to present: (1) method of atlas design and development including design principles, accuracy requirements, atlas content, architecture, functionality, user interface, and customized tools; (2) creation of an atlas of structure and systems including its modeling method and validation; and (3) integration of this atlas with the cerebrovasculature and tracts created earlier. The atlas is created from multiple in vivo 3/7 T scans. Its design based on "pyramidal principle" enables scalability while preserving design principles and exploits interaction paradigm "from blocks to brain". The atlas contains (1) navigator with modules for system/object/object state management, interaction, user interfacing, and rendering; and (2) brain model with cerebrum, cerebellum, brainstem, spinal cord, white matter, deep structures, systems, ventricles, arteries, veins, sinuses, and tracts. The brain model is parcellated, labeled, consistent, realistic, of high resolution, polygonal/volumetric, dissectible, extendable, and deformable. It has over 1700 3D components. The atlas has sub voxel accuracy of 0.1mm and the smallest vessels of 80 MUm. Brain exploration includes dynamic scene composition, manipulation-independent 3D labeling, interaction combined with animation, meta-labeling, and quantification. This atlas is useful in education, research, and clinical applications. It can potentially be foundation for a multi-level molecular-cellular-anatomical physiological-behavioral platform. PMID- 22062452 TI - Fat deposition, fatty acid composition and meat quality: A review. AB - This paper reviews the factors affecting the fatty acid composition of adipose tissue and muscle in pigs, sheep and cattle and shows that a major factor is the total amount of fat. The effects of fatty acid composition on meat quality are also reviewed. Pigs have high levels of polyunsaturated fatty acids (PUFA), including the long chain (C20-22) PUFA in adipose tissue and muscle. The full range of PUFA are also found in sheep adipose tissue and muscle whereas cattle 'conserve' long chain PUFA in muscle phospholipid. Linoleic acid (18:2n-6) is a major ingredient of feeds for all species. Its incorporation into adipose tissue and muscle in relation to the amount in the diet is greater than for other fatty acids. It is deposited in muscle phospholipid at a high level where it and its long chain products eg aracidonic acid (20:4n-6) compete well for insertion into phospholipid molecules. Its proportion in pig adipose tissue declines as fat deposition proceeds and is an index of fatness. The same inverse relationships are not seen in ruminant adipose tissue but in all species the proportion of 18:2n-6 declines in muscle as fat deposition increases. The main reason is that phospholipid, where 18:2n-6 is located, declines as a proportion of muscle lipid and the proportion of neutral lipid, with its higher content of saturated and monounsaturated fatty acids, increases. Oleic acid (18:1cis-9), formed from stearic acid (18:0) by the enzyme stearoyl Co-A desaturase, is a major component of neutral lipid and in ruminants the same enzyme forms conjugated linoleic acid (CLA), an important nutrient in human nutrition. Like 18:2n-6, alpha-linolenic acid (18:3n-3) is an essential fatty acid and is important to ruminants since it is the major fatty acid in grass. However it does not compete well for insertion into phospholipid compared with 18:2n-6 and its incorporation into adipose tissue and muscle is less efficient. Greater biohydrogenation of 18:3n-3 and a long rumen transit time for forage diets also limits the amount available for tissue uptake compared with 18:2n-6 from concentrate diets. A positive feature of grass feeding is that levels of the nutritionally important long chain n-3 PUFA are increased ie EPA (20:5n-3) and DHA (22:6n-3). Future research should focus on increasing n-3 PUFA proportions in lean carcasses and the use of biodiverse pastures and conservation processes which retain the benefits of fresh leafy grass offer opportunities to achieve this. The varying fatty acid compositions of adipose tissue and muscle have profound effects on meat quality. Fatty acid composition determines the firmness/oiliness of adipose tissue and the oxidative stability of muscle, which in turn affects flavour and muscle colour. Vitamin E is an essential nutrient, which stabilises PUFA and has a central role in meat quality, particularly in ruminants. PMID- 22062453 TI - Improving ground beef safety and stabilizing color during irradiation using antioxidants, reductants or TSP. AB - The objective of this research was to extend ground beef retail display life using antioxidants, reductants, and/or TSP treatments combined with electron beam irradiation. Ground beef was produced with added butylated hydroxyanisole (BHA) plus butylated hydroxytoluene (BHT) with the following combinations; (1) ascorbate; (2) trisodium phosphate(buffer); (3) erythorbate; (1) and (2); (1) and (3); (1), (2), and (3); and an untreated control, C. Half of the treated samples were irradiated (I) at 2.0kGy-absorbed dose under a nitrogen atmosphere, half remained non-irradiated (N). Samples were displayed under atmospheric oxygen and evaluated for total aerobic plate count (TPC), thiobarbituric acid reactive substances (TBARS) and instrumental color during 9d of simulated retail display (SRD). Controls had the highest (P<0.05) TBARS value and the lowest (P<0.05) redness (CIE a*), proportion of oxymyoglobin and vividness. Treated irradiated samples were just as red and vivid on SRD day 9 as the non-irradiated untreated control at day 0. Treatments stabilized color and lipids of ground beef after irradiation and during SRD. PMID- 22062454 TI - Effect of muscle location, fiber direction, and slice thickness on the processing characteristics and tenderness of beef stir-fry strips from the round and chuck. AB - The objective was to assess different beef muscles for use as stir-fry. Inside round, outside round, eye of round, knuckle, chuck clod, and chuck tender were obtained from six beef carcasses. Different slice thickness (2, 4, or 8mm) and muscle fiber direction were evaluated. Slices were cooked from frozen on a flat grill and then cut into strips for shear and sensory testing. While meat cut had little effect on shear values of these thin slices, increasing slice thickness greatly affected tenderness and cook yield. The sensory panel found that strips from the knuckle were more tender and juicy, with less connective tissue and with a better flavor than that of slices from the eye of round and outside round. Increasing slice thickness resulted in detection of greater amounts of connective tissue but did not result in a significant difference in the perception of tenderness. Fiber direction was also of importance. Slices removed perpendicular to the fiber direction had shear values up to 50% lower than slices removed parallel. PMID- 22062455 TI - Changes in collagen, texture and sensory properties of meat when selecting rabbits for growth rate. AB - The consequences of selection for growth rate and the associated decrease of maturity at slaughter in rabbits on collagen content, collagen solubility, meat texture (Warner-Bratzler shear device) and the sensory properties of the m. Longissimus were studied. Sixty rabbits from the 7th generation of a line selected for growth rate (group C) were compared to 60 rabbits from the 23rd generation of the same line (group S). Both groups were contemporarily reared and slaughtered at 2000g. No changes on collagen content were found, but group S had a higher (5%) collagen solubility. Shear force, shear firmness and area or total work needed to cut the sample were not different between groups, and hardness evaluated in the panel test was not relevantly changed. Most of the sensory properties studied did not differ relevantly between groups. Group S had 8% less aniseed odour and 10% more juiciness. PMID- 22062456 TI - Use of starter cultures of dairy origin in the production of Salame nostrano, an Italian dry-cured sausage. AB - The aim of this study was the evaluation of the use of selected lactic acid bacteria (LAB) starter culture of dairy origin in the production of low-acid fermented sausages (Salame nostrano) produced in a small-scale plant in Umbria (Italy), and their effect on microbiological, physico-chemical and sensorial properties of the products. Salame nostrano was obtained with two different technological processes: with and without the addition of selected LAB starter cultures. Microbial counts of safety indicators were lower in salami made with the addition of starter cultures. Pathogens after the first week of ripening were only detected from salami made without the addition of starter cultures. Control salami were rated as paler and harder, whereas those made with the addition of starter cultures as slightly saltier, juicier and in general more acceptable. Selected dairy-origin starter (SDS) cultures did prevent the growth of safety indicators, greatly reduced the rate of isolation of pathogens and increased the acceptability of full-ripened salami. PMID- 22062457 TI - Quantitative analysis of pork dry-cured sausages to quality control by NIR spectroscopy. AB - Near infrared spectroscopy technology (diode array instrument) was used to study the feasibility of applying quality controls to typical Spanish sausages by performing a proximate analysis (fat, moisture and protein) on the finished product (intact and homogenized). This could be used to provide quality controls at various stages once the finished product was obtained: finished product, storage, distribution and marketing. The selected models were calibrated and evaluated by cross and external validation. For intact products, coefficients of determination for calibration (R(2)) for fat, moisture and protein were 0.98, 0.93 and 0.97, respectively. These values for homogenised products were 0.99, 0.98 and 0.97, respectively. The standard errors of prediction (SEP) for external validation in intact products were 1.47%, 0.97% and 1.08% for fat, moisture and protein, respectively. In homogenised products, these values were lower: 0.71%, 0.41% and 0.95%, respectively. PMID- 22062458 TI - Predicting the composition of lamb carcases using alternative fat and muscle depth measures. AB - Hot carcase weight (HCW) and the GR tissue depth (total tissue depth over the 12th rib, 110mm from the midline) were measured on 312 crossbred (Poll Dorset*Merino) lambs with a mean live weight of 47kg. At a position 30mm distal to the lumbar-sacral junction, the depth (RMD) of the rump muscles was measured along with subcutaneous fat depth overlaying the m. gluteus medius (RFD). The subcutaneous fat depth over the m. longissimus (loin) at the 12th rib was measured (Fat C), as was the depth and width of the loin cross section (EMD and EMW, respectively). The right side of each carcase was scanned by a dual energy X ray bone densitometer and fat and lean weight determined and the percentage of lean and fat content in the carcases calculated. HCW alone accounted for 26% of the variation in percentage lean content (LC), with GR measurement being the single best predictor of LC (R(2)=48.1; r.s.d.=1.89). RFD provided a less accurate and precise estimate of LC (R(2)=37.3; r.s.d.=2.07) than either GR or Fat C (R(2)=46.5; r.s.d.=1.92). Inclusion of HCW with either GR or Fat C provided a small improvement in the amount of variation in LC which could be explained. The measurement of breeding animals by ultrasound includes the terms weight, Fat C and EMD. These predictors when combined explained 49% of the variation in LC whereas by comparison measures of weight, RFD and RMD only explained 42% of the variation in LC. The current method of measuring fat depth over the 12th/13th rib is practical and measurement over the rump does not present an advantage based on the results of this study. PMID- 22062459 TI - Low-fat sodium-reduced sausages: Effect of the interaction between locust bean gum, potato starch and kappa-carrageenan by a mixture design approach. AB - A mixture design approach was used to evaluate interactions between potato starch, locust bean gum and kappa-carrageenan and their effect on cooking yield, expressible moisture, texture and color in low-fat sodium-reduced sausages formulated with potassium and calcium chloride. Starch had a notable influence on cooking yield and texture, increasing product hardness and resilience as starch proportion increased. The added salt did not allow complete starch granule gelatinization and swelling, which negatively affected water retention, cohesiveness and lightness. Locust bean gum and kappa-carrageenan improved cooking yield and reduced expressible moisture in formulations containing higher proportions of potato starch. The presence of other ions could have enhanced kappa-carrageenan functionality and its synergistic interaction with locust bean gum, improving texture and water retention, with only minor effects on sausage color. At the lower tested proportions starch can be used as an extender in low fat cooked meat products if kappa-carrageenan and locust bean gum are included in similar proportions. PMID- 22062460 TI - Microbiological quality of freshly shot game in Germany. AB - In the framework of a project on the hygiene status of freshly shot game 289 samples were microbiologically analysed: 127 samples from wild boars, 95 from roe deer and 67 from red deer. The microbiological parameters evaluated were the mesophilic aerobic count (APC), which showed mean log10-counts of 2.6cfu/cm(2) for roe deer, 2.9cfu/cm(2) for red deer and 3.2cfu/cm(2) for wild boars and the numbers of Enterobacteriaceae, which gave mean log10-values of 2.1cfu/cm(2) for all three species with differing ranges. The concentrations of coagulase positive staphylococci were >2.0 log10cfu/cm(2) between 3.2 and 6.3%, according to species. Listeria was found in 14 samples and three samples gave a positive result for Campylobacter. Salmonella was not found in any of the samples analysed. PMID- 22062461 TI - Influence of sex and terminal sire line on performance and carcass and meat quality of Iberian pigs reared under intensive production systems. AB - A trial was conducted to study the effects of sex (castrated males; females) and terminal sire line (DD, Danish Duroc; SD, Spanish Duroc; RIB, Retinto Iberian) on performance and carcass and meat quality of pigs slaughtered at 145kg body weight. The female line was pure Iberian in all cases. Each treatment was replicated five times (six pigs). Females were more efficient, had less carcass and inter- and intramuscular fat and more trimmed primal cuts yield than castrated males. Duroc sired pigs grew faster and had better feed conversion and carcass quality than RIB sired pigs. Crossbreeds from SD had less carcass yield than crossbreeds from DD or RIB. We conclude that productive performance and primal cuts yield were higher for females than for castrated males. Danish Duroc sires are an alternative to Spanish Duroc and Retinto Iberian sires for production of heavy pigs destined for the dry cured industry. PMID- 22062462 TI - The influence of cooking rate and holding time on beef chuck and round flavor. AB - Steaks from seven muscles from 10 beef carcasses were cooked quickly or slowly and held 0 or 1h to explore the influence of cooking rate and holding time on beef flavor. Moisture, ash, pH, and heme-iron concentration were determined for each muscle. Trained sensory panels evaluated the steaks for tenderness, juiciness, connective tissue, and off-flavor intensity in addition to identifying specific off-flavors. Off-flavor intensity was lowest when beef was cooked slowly (on a 149 degrees C gas grill instead of a 249 degrees C grill) and when it was held for 1h prior to sensory evaluation. The M. infraspinatus had the least intense off-flavor and the M. vastus intermedius had the most intense off-flavor. Slow cooking or holding for 1h prior to consumption reduced the intensity of off flavor in value cuts from the beef chuck and round while chemical characteristics did not contribute to off-flavor in this study. PMID- 22062463 TI - Addition of grape seed extract and bearberry to porcine diets: Influence on quality attributes of raw and cooked pork. AB - The effect of supplementation of pig diets with grape seed extract (GSE) (100, 300, 700mg/kg feed) and bearberry (BB) (100, 300, 700mg/kg feed) for 56 days pre slaughter, on the oxidative stability and quality of raw and cooked M. longissimus dorsi (LD) was examined. Susceptibility of porcine liver, kidney and heart tissue homogenates to iron-induced (1mM FeSO(4)) lipid oxidation was also investigated. In raw LD steaks, stored in modified atmosphere packs (75% O(2):25% CO(2)) (MAP) for up to 16 days at 4 degrees C, surface lightness (CIE 'L' value), redness (CIE 'a' value), lipid stability (TBARS, mg MDA (malondialdehyde)/kg muscle) and pH were not significantly affected by supplemental GSE or BB. Similarly, the oxidative stability and sensory properties of cooked LD steaks, stored in MAP (70% N(2):30% CO(2)), for up to 28 days at 4 degrees C, were not enhanced by dietary GSE or BB. Iron-induced lipid oxidation increased in liver, kidney and heart tissue homogenates over the 24h storage period and susceptibility to oxidation followed the order: liver>heart>kidney. Dietary GSE or BB did not significantly reduce lipid oxidation in tissue homogenates. Potential reasons for the lack of efficacy of supplemental GSE and BB on pork quality were explored. PMID- 22062464 TI - Effect of replacing beef fat with hazelnut oil on quality characteristics of sucuk - A Turkish fermented sausage. AB - Turkish fermented sausages (sucuk) were produced by replacing 15, 30 and 50% of beef fat with hazelnut oil incorporated as pre-emulsified with simplesse((r)) 100 (whey protein powder) Each treatment was formulated to contain 20% total fat and beef fat was the only fat material used in the control (C) group. After 12 days of fermentation and ripening, all sucuk samples had TBA values within acceptable limits (<1.0). Increasing levels of hazelnut oil in sucuk formulation increased penetrometer values (softer texture) and moisture content. Hazelnut oil replacement had a significant effect on redness values of the samples. Cholesterol content decreased progressively as the percentage of hazelnut oil increased in the formulation. Replacement of 50% beef fat with 50% hazelnut oil significantly increased MUFA, PUFA and MUFA+PUFA/SFA ratios. The use of hazelnut oil resulted in significant decreases in the slice appearance, texture and taste scores. However there was no significant difference in the overall acceptability score of samples, except those in which hazelnut oil replaced 15% beef fat, which had the highest score. PMID- 22062465 TI - Comparisons of longissimus muscle metabolic enzymes and muscle fiber types in Korean and western pig breeds. AB - We compared differentially expressed genes and muscle fiber types in the longissimus muscles of Korean native pigs (KNP) and the western meat-producing breeds Landrace and Yorkshire. The KNP breed exhibited a higher muscle fat content and more red meat color as determined by the a(*) (redness) value (P<0.01) and b(*) (yellowness) value (P<0.05) compared to the western breeds. Using differential display RT-PCR, we detected two genes that were differentially expressed in skeletal muscle among the pig breeds. These genes were identified as NADH dehydrogenase subunit 1 and ATPase subunit 6 by cloning and sequencing analysis. Both of these genes are involved oxidative phosphorylation and therefore energy metabolism. The genes were more highly expressed in the KNP breed than in the other breeds, indicating that KNPs exhibit more oxidative metabolism than do the western breeds. We also analyzed the mRNA levels of myosin heavy-chain isoforms such as type I (oxidative), type IIb (glycolytic), and types IIa and IIx (intermediate) fibers using real-time RT-PCR. The mRNA levels of oxidative and intermediate fibers were elevated in the KNP breed, whereas the glycolytic fibers were more highly expressed in the Landrace and Yorkshire pigs. These results suggest that the elevated expression of the oxidation-related metabolism genes NADH dehydrogenase and ATPase is related to meat quality as indicated by a higher content of oxidative fibers and muscle fat, as well as redder meat color. PMID- 22062466 TI - Antioxidant effect of Cassia essential oil on deep-fried beef during the frying process. AB - The object of the research was to determine the antioxidant effect of cassia essential oil on deep-fried beef during the frying process. The rules and optimum processing conditions of deep-fried beef with addition of cassia essential oil were discussed through an orthogonal experiment and some single factor experiments (frying time, frying temperature, oil types and concentration of essential oil). The antioxidant effect was evaluated by peroxide and TBA value. Results showed that the antioxidant effect of cassia oil during the frying process was optimum under the conditions of 30MUL cassia oil/250mL palm oil, 1.5min at 150 degrees C. The main compositions of cassia oil were analysed by GC MS method. PMID- 22062467 TI - Effect of silk flower hay (Calotropis procera Sw) feeding on the physical and chemical quality of Longissimus dorsi muscle of Santa Inez lambs. AB - The effect of different levels of silk flower hay (Calotropis procera Sw) in the diet of confined lambs by the substitution of the commonly used foraging broom corn hay (Sorghum bicolor L) was investigated to evaluate its possible effects on the growth and quality of the lamb meat. Twenty-four male Santa Inez lambs were divided in equal numbers into four treatment groups and fed diets containing 0%, 16.7%, 33.3% and 50% of silk flower hay (SFH). Growth rate, feed intake and meat quality were investigated. Mean daily gains of lambs were 170g for control, 180.5g for 16.7% SFH, 96.8g for 33.3% SFH and 22.9g for 50% SFH. The use of silk flower hay in the diet of Santa Inez lambs affected health of the animals and meat pH when the substitution of the forage was high, up to 50%; however, the general meat quality was not affected. Meat from animals fed with levels up to 50% SFH had physical (Aw, a(*), b(*) and L(*)) and chemical (moisture, ash, lipid, phosphorus, iron, phospholipid and fatty-acid profile) parameters comparable to the control group (0% SFH). Among the various levels of substitution (16.7%, 33.3% and 50%) of silk flower hay in the diet tried in this work, the use of 16.7% was found to be an attractive and technically viable option for the Northeast region of Brazil. PMID- 22062468 TI - Characterisation of microbial deep spoilage in Iberian dry-cured ham. AB - The purpose of this work was to investigate the micro-organisms involved in overlooked "bone taint" spoilage of dry-cured Iberian hams. The physico-chemical characteristics of spoiled hams with 12 and 24 months of ripening, showing initial signs of alteration, were analyzed and their correlations with microbial counts studied. The spoilage potential of different microbial groups was assessed by the relationship between the microbial counts and the proteolysis level of spoilage as observed in the degradation of myofribrillar and sarcoplasmic protein fractions and in the changes in free amino acids. Non-enteric gram-negative bacteria (NEGN) were the dominant microbial group, showing a positive correlation with the moisture of spoiled hams. The Catalase-positive cocci (GPCP) growth was favoured by high NaCl concentrations in the spoiled hams, whereas the counts of Enterobacteriaceae were negatively affected by high NaCl concentration. The highest proteolytic microorganisms were the Gram-negative microbial groups playing Enterobacteriaceae a major role in the undesirable changes of the texture properties of the spoiled hams. With respect to the sensorial analysis, a synergy between NEGN and GPCP was observed in most of the strongly spoiled samples. PMID- 22062469 TI - Effect of genetic rabbit lines on lipid content, lipolytic activities and fatty acid composition of hind leg meat and perirenal fat. AB - The influence of genetic origin on lipid content, lipolytic activities and fatty acid composition of rabbit leg meat and perirenal fat was studied and changes in free fatty acids and oxidative parameters during refrigerated storage evaluated. Three rabbits lines were used, line R selected for growth rate and lines V and A selected for litter size at weaning. Line R had higher fat contents and higher lipolytic activities in the meat of the hind leg than lines A and V. Differences between lines were found in the fatty acids of the meat and perirenal fat. Lower SFA and higher PUFA percentages were found in line A. Free fatty acids and oxidative parameters were little influenced by rabbit line. Animals were measured at the same stage of maturity, thus it can be considered that differences found between lines are genetic differences and not differences due to the degree of maturity. PMID- 22062470 TI - Colour formation in fermented sausages by meat-associated staphylococci with different nitrite- and nitrate-reductase activities. AB - Three Staphylococcus strains, S. carnosus, S. simulans and S. saprophyticus, selected due to their varying nitrite and/or nitrate-reductase activities, were used to initiate colour formation during sausage fermentation. During fermentation of sausages with either nitrite or nitrate added, colour was followed by L(*)a(*)b measurements and the content of nitrosylmyoglobin (MbFe(II)NO) quantified by electron spin resonance (ESR). MbFe(II)NO was rapidly formed in sausages with added nitrite independent of the presence of nitrite reducing bacteria, whereas the rate of MbFe(II)NO formation in sausages with added nitrate depended on the specific Staphylococcus strain. Strains with high nitrate-reductase activity showed a significantly faster rate of pigment formation, but other factors were of influence as well. Product stability for the sliced, packaged sausage was evaluated as surface colour and oxidation by autofluorescence and hexanal content, respectively. No significant direct effect of the Staphylococcus addition was observed, however, there was a clear correspondence between high initial amount of MbFe(II)NO in the different sausages and the colour stability during storage. Autofluorescence data correlated well with hexanal content, and may be used as predictive tools. Overall, nitrite- and nitrate-reductase activities of Staphylococcus strains in nitrite-cured sausages were of limited importance regarding colour development, while in nitrate-cured sausages strains with higher nitrate reductase activity were crucial for ensuring optimal colour formation during initial fermentation stages. PMID- 22062471 TI - Muscle fiber and fatty acid profiles of Mertolenga-PDO meat. AB - The influence of phenotype and muscle type on intramuscular total lipids (ITL) neutral lipid (NL) and phospholipid (PL) compositions, cholesterol, alpha tocopherol and haem iron contents were evaluated in Semitendinosus (St), Longissimus dorsi (Ld) and Supraspinatus (Ss) muscles from 39 Mertolenga young bulls. The results showed that lipid, alpha-tocopherol, cholesterol and haemic iron contents were not influenced by phenotype. Furthermore, the individual effect of phenotype was not a significant source of variation on ITL, NL and PL fatty acid composition. Muscle histological traits from Unicolor phenotype (n=13) showed that Ss and Ld muscles exhibited higher proportion of type I (P<0.001) and oxidative fibers (P<0.001) and lower percentages of IIB fibers (P<0.001) than St. The Ss muscle, with higher relative area occupied by oxidative fibers (P<0.05 0.001) than Ld and St, had higher ITL (P<0.001), NL (P<0.001), PL (P<0.05-0.01), alpha-tocopherol (P<0.001), cholesterol (P<0.01) and haem iron (P<0.001) contents than its counterparts. Muscle type notably affected ITL, as a result of its influence on NL rather than in PL composition. PMID- 22062472 TI - Screening for anti-listerial bacteriocin-producing lactic acid bacteria from "Gueddid" a traditionally Tunisian fermented meat. AB - Forty eight lactic acid bacteria strains isolated from "Gueddid", a traditionally Tunisian fermented meat, were screened for bacteriocin production. Four strains named MMZ 04, 09, 13, and 17 showed antimicrobial activity and were identified as Enterococcus faecium by molecular methods based on the 16S-23S rDNA ISR, PCR-RFLP analysis of the 16S-23S rDNA ISR and species-specific primers. The four antimicrobial compounds were heat stable (121 degrees C for 15min), active over a wide pH range (3-9) and the antimicrobial activity was lost after treatment with trypsin, alpha-chymotrypsin and proteinase K but not by lysozyme and lipase. The mode of action of enterocin MMZ17 was identified as bactericidal. The MMZ17 bacteriocin was partially purified by ammonium sulphate precipitation and C(18) Sep-Pack chromatography. The apparent molecular size of enterocin MMZ17 as indicated by activity detection after SDS-PAGE was lower than 6.5 KDa. According to these assays, enterocin MMZ17 can be classified as a small, heat-stable Listeria-active peptide, presumably belonging to class IIa bacteriocins. PMID- 22062473 TI - Effect of processing on functional properties of animal blood plasma. AB - A number of functional and physical properties such as solubility, foam capacity, emulsifying stability and interfacial tension were compared for standard plasma, plasma decationed by ion exchange and plasma deionized by ultrafiltration (UF). The changes in functional properties can determine the use of a protein as an additive to a food product or invalidate its use. All samples had good functional properties and hence could be used in the formulation of food products. Results showed that ion exchange and UF improved emulsifying capacity while having little effect on the other functional properties. PMID- 22062474 TI - Sodium lactate influences myoglobin redox stability in vitro. AB - Injection-enhancement of beef with lactate improves color stability; however, the mechanism is unclear. Thus, our objectives were to assess the effects of sodium lactate on equine myoglobin redox stability in vitro. Oxymyoglobin at pH 5.6 (50mM sodium citrate) and pH 7.4 (50mM sodium phosphate) was incubated at 4 degrees C with lactate (0, 5, 10, 100, or 200mM) and myoglobin redox form was determined using absorbance spectra. Metmyoglobin formation at pH 5.6 and 7.4 was significantly (P<0.05) decreased by lactate at concentrations of 100 and 200mM. In general, increasing lactate concentration from 100 to 200mM increased (P<0.05) oxymyoglobin redox stability. This effect of lactate on myoglobin redox stability could be partially responsible for the improved color stability associated with lactate injection-enhanced beef products. Further work should determine the effect of lactate on beef myoglobin. PMID- 22062475 TI - Dissection of the functional domains of an archaeal Holliday junction helicase. AB - Helicases and nucleases form complexes that play very important roles in DNA repair pathways some of which interact with each other at Holliday junctions. In this study, we present in vitro and in vivo analysis of Hjm and its interaction with Hjc in Sulfolobus. In vitro studies employed Hjm from the hyperthermophilic archaeon Sulfolobus tokodaii (StoHjm) and its truncated derivatives, and characterization of the StoHjm proteins revealed that the N-terminal module (residues 1-431) alone was capable of ATP hydrolysis and DNA binding, while the C terminal one (residues 415-704) was responsible for regulating the helicase activity. The region involved in StoHjm-StoHjc (Hjc from S. tokodaii) interaction was identified as part of domain II, domain III (Winged Helix motif), and domain IV (residues 366-645) for StoHjm. We present evidence supporting that StoHjc regulates the helicase activity of StoHjm by inducing conformation change of the enzyme. Furthermore, StoHjm is able to prevent the formation of Hjc/HJ high complex, suggesting a regulation mechanism of Hjm to the activity of Hjc. We show that Hjm is essential for cell viability using recently developed genetic system and mutant propagation assay, suggesting that Hjm/Hjc mediated resolution of stalled replication forks is of crucial importance in archaea. A tentative pathway with which Hjm/Hjc interaction could have occurred at stalled replication forks is discussed. PMID- 22062476 TI - Changes in concentration of sarcoplasmic free calcium during post-mortem ageing of meat. AB - We studied post-mortem changes in the concentrations of sarcoplasmic free calcium in various meats to clarify the tenderisation mechanism of meat, taking sufficient care to prevent contamination with calcium ions other than those in meat. When minced meats were homogenised and concentrations of soluble calcium ions were determined by atomic absorption spectrophotometry, it was found that the concentration of free calcium increased, the rate of increase varying depending on the species, and reached a narrow range of 210-230MUM regardless of the anatomical class of skeletal muscle, chronological ageing or animal and fowl species. The calcium concentration was 100nM immediately post-mortem when homogenisation was performed in the presence of 2 mM ATP. Phospholipids were liberated from the sarcoplasmic reticulum during ageing of meat. It is likely that calcium ions leak into the sarcoplasm through channels formed by phospholipid liberation. PMID- 22062477 TI - Effects of mid-summer transport duration on pre- and post-slaughter performance and pork quality in Mexico. AB - Seven hundred and fourteen pigs were monitored from transport to slaughter in July in three treatments: 8, 16 and 24 transport hours; lairage time for the three groups was of 8h. Transport duration significantly (P<0.05) affected live weight gain during the rest period. Weight gain percentages at lairage were 0.05%, 0.78% and 1.15% for treatments 1, 2 and 3, respectively. Transport to slaughter loss percentage was 2.7%, 4.3% and 6.8% for each of the treatments. Short transport periods significantly increased carcass pH below normal values. Animals transported under acute stress (8h) showed pale carcasses (high possibilities of transforming into PSE meat). On the contrary, pigs transported for 24h had more dark red carcasses. Transport from farm to the slaughterhouse should take no more than 16h in order to improve carcass quality and animals' welfare. PMID- 22062478 TI - The pre- and post-grinding application of rosemary and its effects on lipid oxidation and color during storage of ground beef. AB - The timing of the application of rosemary extract was evaluated as one-way of minimizing myoglobin and lipid oxidation in ground beef. In experiment 1, rosemary extract was added to beef at four different stages namely trim, cube, coarse, and fine ground beef. The beef was evaluated for color and TBARS values during 144h of storage (4 degrees C). Results showed that when rosemary was added to the pre-grinding treatments of trim and cube, ground beef had the highest a(*) values (redness), oxymyoglobin content, and lowest TBARS values at 144h. In experiment 2, the effect of rosemary extract was evaluated on the color quality of case ready ground beef inoculated with 10(7)CFU/g Escherichia coli. Microbial counts, color, and TBARS values were measured during 144h of simulated storage. The results showed that both the rosemary treated samples that were inoculated and uninoculated remained redder longer and had lower TBARS values than the untreated inoculated and uninoculated controls. There was no significant inhibition of E. coli by the rosemary extract. PMID- 22062479 TI - Mechanical properties of type I and type IIB single porcine muscle fibres. AB - Single muscle fibres were isolated from longissimus dorsi (LD) and vastus intermedius muscles at 1 or 8 days post-mortem. Fibres were classified as type I or IIB and their mechanical properties determined. In LD day 1, individual type IIB fibres fractured at higher (P<0.001) loads and lower (P<0.001) stress values than type I fibres. The strength of type I fibres did not differ between muscles. Storage for 8 days decreased (P<0.001) breaking stress of type I fibres, whereas the breaking stress of type IIB fibres did not change. In conclusion, type IIB fibres were weaker per cross-sectional area than type I fibres in LD. The mechanical properties of type I fibres did not differ between muscles and the change in strength with post-mortem storage were more marked in type I than in type IIB fibres. PMID- 22062480 TI - Comparison of the relative expression of caspase isoforms in different porcine skeletal muscles. AB - The present study investigated the relationship between muscle type and components of the caspase protease system in porcine trapezius (TZ), psoas (PS), longissimus dorsi (LD) and semitendinosus (ST) muscles. Muscles were classified according to slow and fast myosin heavy chain (MHC) content determined by western blotting. MHC slow, but not MHC fast protein expression was significantly different between muscles (p<0.001). Protein levels of caspases 3, 8 and 12 and the caspase inhibitor apoptosis repressor with caspase recruitment domain (ARC) were determined. In addition the level of caspase 3 mRNA and activity levels of caspase 3/7 were determined. There was a significant difference in protein levels and activity between muscles (p<0.01), although no difference was observed in mRNA abundance. The data show that multiple components of the caspase system are expressed in porcine skeletal muscle and that their levels are variable, but there is not a distinct association of expression with a particular muscle. PMID- 22062481 TI - Lipid characteristics of subcutaneous adipose tissue and M. longissimus thoracis of Angus and Wagyu steers fed to US and Japanese endpoints. AB - We hypothesized that the concentrations of monounsaturated fatty acids (MUFA) and cholesterol of adipose tissue and M. longissimus thoracis would not differ between Angus and American Wagyu steers when fed to a typical US live weight, but would diverge when fed to a Japanese live weight. To test this, 8 steers of each breed type were assigned to a high-energy, corn-based diet, and another 8 steers of each breed type were fed coastal bermuda grass hay diet, supplemented with the corn-based diet to achieve a daily gain of 0.9kg/d. Targeted final body weights were 525kg for steers fed for 8 or 12mo the corn- or hay-based diets, respectively, and were 650kg for steers fed for 16 or 20mo the corn- or hay-based diets. Digesta concentrations of stearic (18:0) and trans-vaccenic acid decreased, whereas linoleic acid (18:2n-6) increased between the US and Japanese endpoints (all P?0.03). alpha-Linolenic acid (18:3n-3) increased in digesta only in the hay-fed steers during this time. Plasma concentrations of palmitic (16:0) and palmitoleic acid (16:1n-7), and the 16:1:18:0 ratio, were higher in Angus steers than in Wagyu steers. Also, the plasma 16:1:18:0 ratio was decreased by hay feeding in Angus steers, but increased in Wagyu steers, when fed to the Japanese endpoint. Concentrations of oleic (18:1n-9), linoleic, alpha-linolenic, and 18:2trans-10,cis-12 conjugated linoleic acid all were higher in Wagyu than in Angus subcutaneous (s.c.) adipose tissue, whereas myristic (14:0) and palmitic acid were higher in Angus s.c. adipose tissue (P?0.05). All MUFA increased, and saturated fatty acids decreased, between the US and Japanese endpoints. Slip points of lipids in s.c. adipose tissue were over 10 degrees C lower (P=0.01) in Japanese-endpoint steers than in US endpoint steers, consistent with the overall increase in MUFA with time on feed. The concentration of cholesterol in the M. longissimus thoracis increased with time, which may have been related to the increase in oleic acid. Because the breed*endpoint interaction was not significant for cholesterol or any of the adipose tissue fatty acids, we conclude that our original hypothesis was incorrect. Of the three factors tested (breed type, diet, and slaughter age endpoint), endpoint had the greatest effect on adipose tissue lipid composition. PMID- 22062482 TI - Utilization of natural antioxidants: Green tea extract and Thymbra spicata oil in Turkish dry-fermented sausage. AB - Effect of natural (green tea extract, Thymbra spicata oil) and synthetic antioxidants (buthylatedhydroxytoluene, BHT) on the safety (biogenic amine and TBARS values) and quality (pH, colour and sensory attributes) of sucuk (Turkish dry-fermented sausage) were investigated during the ripening periods. Addition of antioxidants decreased (P<0.05) the TBARS values. It was found that natural antioxidants decreased TBARS formation more than BHT. Antioxidants reduced (P<0.05) putrescine formation in the following order: green tea extract>green tea extract-T. spicata oil>T. spicata oil>BHT, and their mean values were 70.45, 76.05, 83.13, and 95.97mg/kg, respectively. The highest tyramine concentration was observed in control sucuk prepared without any antioxidants, while the lowest was in the recipe with green tea extract as their mean values were about 99.42 and 64.31mg/kg, respectively. The pH, L, b, and overall sensory quality were not significantly different (P>0.05) with the addition of green tea extract, T. spicata oil, green tea extract-T. spicata oil. These results indicated that the most effective antioxidant was found to be green tea extract. This study pointed out that natural antioxidants were more effective than synthetic antioxidants, so they could be easily utilized in sucuk to enhance quality and provide safer products. PMID- 22062483 TI - Influence of maturation and cooking treatments on the nutritional value of bovine meats: Water losses and vitamin B12. AB - The aim of the study was to determine the influence of maturation and of cooking processes on water losses and on the vitamin B12 content of meat. Three types of muscle (Longissimus lumborum, Longissimus thoracis and Triceps brachii) were sampled from a total of 16 animals, representative of animals raised for meat production in France. Three durations of maturation were compared: 1, 3 and 14 days. Different cooking processes were applied: Longissimus lumborum was deep-fat fried or roasted, Longissimus thoracis was pan fried or grilled and Triceps brachii was braised. The cooking yield averaged 55-56% for Triceps brachii, 73 77% for Longissimus lumborum and 85-87% for Longissimus thoracis. Vitamin B12 concentration in raw meat was significantly higher in Triceps brachii than in Longissimus lumborum and Longissimus thoracis (20.86, 11.53 and 9.21ng/g wet tissue, in the same respective order). When expressed on a wet weight basis, all concentrations were significantly increased by cooking. When expressed on a lipid free dry basis, significant losses in vitamin B12 were measured only in the braised Triceps brachii (-25%) and in the deep-fat fried Longissimus lumborum ( 5.5%) as a result of long duration and high temperature of cooking, respectively. Maturation did not affect the vitamin B12 content of meat, whether raw or cooked. PMID- 22062484 TI - Functional properties of pre-rigor, pre-salted ground beef chilled with solid carbon dioxide. AB - Ground, pre-salted, pre-rigor semimembranosus muscles of beef were subjected to three treatments A=rapid carbon dioxide (CO(2)) chilling, B=slow CO(2) chilling and C=air chilling, and compared to a control D=slow air chilling of muscles, which were subsequently ground and salted post-rigor. Meat of the pre-rigor treatments A, B and C had higher pH values during processing, lower cooking loss, firmer texture and a lighter yellowish external colour of cooked patties than the post-rigor control D (p<0.05). The two CO(2) chilling regimes A and B had no detrimental effects on the functional properties of the pre-rigor meat. Sarcomere lengths did not differ in meat of the four treatments (p>0.05), indicating that early pre-salting protected the meat from cold shortening during rapid temperature decline. A process combination of grinding, followed by immediate pre salting and CO(2) chilling within 312h post-mortem of non-stimulated beef muscles is likely to yield superior binding properties of cooked patties and similar ground beef products. PMID- 22062485 TI - Meat cooking shrinkage: Measurement of a new meat quality parameter. AB - A parameter, meat cooking shrinkage (MCS), has been introduced based on investigations carried out on meat shrinkage caused by heat during cooking. MCS is the difference between the raw and cooked areas of the meat sample, expressed as a percentage of the raw area. The method uses a disk of meat (10mm thick and 55mm wide) measured before and after cooking in a hot air oven at 165 degrees C for 10min, the meat having reached an internal temperature of 70 degrees C. Video image analysis was used to measure the meat sample area. The proposed MCS protocol permits us to measure cooking loss and to reduce cost and variability, moreover it could be improved to obtain color and marbling measurements by developing the image analysis software. Analysing two or more parameters on the same sample, the correlations among them should improve analysis efficacy. A detailed description of the measurement protocol of MCS is reported as well as its application to beef and pork. PMID- 22062486 TI - Factors influencing the variation in tenderness of seven major beef muscles from three Angus and Brahman breed crosses. AB - Beef carcasses (n=30) from 3/4 Angus (A)*1/4 Brahman (B), 1/4A*3/4B, and 1/2A*1/2B F(1) crosses were used to evaluate breed type, electrical stimulation, and postmortem aging on the M. semimembranosus (SM), M. semitendinosus (ST), M. biceps femoris (BF), M. vastus lateralis (VL), M. gluteus medius (GM), M. longissimus dorsi lumborum (LD), and M. triceps brachii (TB). Shear force values decreased with increased postmortem aging to a greater extent in steaks from 3/4A*1/4B than steaks from the other breed types. Shear force values for steaks from the round (SM, ST, BF, VL) were higher than steaks from the loin (LD, GM) and chuck (TB) for both electrically stimulated and non-electrically stimulated muscles. In the LD muscle, calpastatin activities were similar among breed types. Muscle type played the greatest role in determining tenderness. PMID- 22062487 TI - Consumer attitude towards sodium reduction in meat products and acceptability of fermented sausages with reduced sodium content. AB - Lowering salt content in meat products is possible from a technological and sensorial point of view, although little information is available about the consumers' attitude and acceptance of these products. Attitude towards low salt meat products, following the Theory of Planned Behaviour (TPB) proposed by Ajzen, was evaluated by 392 consumers. Acceptability of small calibre fermented sausages with 50% molar substitution of NaCl by six different mixtures of KCl (0-50%) and K-lactate (0-50%) and the control (22g NaCl/kg) was determined by 98 consumers. The preference of the previous best two treatments was compared to the batch control by 279 consumers. In general consumers had a positive attitude towards low salt meat products, being higher for women than for men. Women showed stronger ideas and higher Perceived Control on the Behaviour towards reduced sodium meat products than men. Smokers showed lower intense beliefs than non smokers. Consumers with a basic level of education were more affected by what other people important for them thought they should do. The final model obtained using the Theory of Planned Behaviour showed a good predictive capacity (R(2)=0.60) and a good internal consistency. Regarding the acceptability study, batches with substitution levels of 50% and 40% by K-lactate, showed lower overall acceptance than the control batch. Significant differences in acceptability were found regarding the gender and place of residence of the consumers. The preference study showed no differences between the batch control and batches with 50% KCl and 40% KCl + 10% of K-lactate substitution levels. According to these results and from a sensorial point of view, it is possible to reduce NaCl content in small calibre fermented sausages by 50% and obtain a product acceptable for consumers. PMID- 22062488 TI - Determination and evaluation of the parameters affecting the choice of veal meat of the "Ternera de Aliste" quality appellation. AB - The aim of the present work was to determine and assess the parameters affecting the choice of veal under the "Ternera de Aliste" quality appellation. The parameters affecting the choice proved to be colour, taste, odour, hardness and juiciness. Using these parameters, sensory evaluation, both analytical (with trained judges, QDA) and affective (with consumers, the home-use test) was carried out on four veal types, and the relative preferences for the samples assessed. Colour, hardness and losses due to cooking were also analysed instrumentally. The results revealed that the methodology is important for discriminating small differences between samples. The same trend was observed for the results of the panel of judges, consumers, and instrumental analyses regarding both hardness and juiciness. Regarding the determinant parameters in the choice of veal, in raw meat consumers prefer light colours but when expressing their general relative preferences for samples, juiciness, taste and hardness of the cooked meat had the greatest weight. PMID- 22062489 TI - Effects of temperature, oxygen exclusion, and storage on the microbial loads and pH of packed ostrich steaks. AB - Ostrich steaks (96) were packed (air or vacuum) and stored at 4 degrees C or 10 degrees C. Microbiological loads (total viable counts - TVC, psychrotrophic, Enterobacteriaceae, lactic acid bacteria - LAB, Pseudomonas and fluorescent Pseudomonas) and pH values were determined at 0, 3, 6 and 9 days. High counts (8.0-10.2 log(10)cfu TVC/g) were observed at day 9, possibly as a consequence of the initial high microbial load (range 4.9-5.4 log(10)cfu TVC/g) and pH (average 6.7). Temperature and sampling day significantly influenced all microbial counts. Gas atmosphere had a small or negligible influence on levels of Enterobacteriaceae and LAB. For most microbial groups temperature significantly influenced bacterial levels up to day 6 of storage, while gas atmosphere had a significant effect at days 6 and 9. Both effects (temperature and gas atmosphere) were significant factors from day 0 for fluorescent Pseudomonas. Samples vacuum packed and stored at 4 degrees C showed the lowest microbial loads at day 9. Only for these samples was no sensory rejection observed at the end of the experiment. PMID- 22062490 TI - Effects of packaging atmospheres on shelf-life quality of ground ostrich meat. AB - Fresh ground ostrich meat was packaged under high oxygen (O2), high nitrogen (N2), vacuum (VAC) and ambient air (AIR) atmospheres, stored at 4+/-1 degrees C and displayed under 1700+/-100lux of fluorescent lighting for 9 days. The meat was evaluated for changes in typical shelf-life characteristics consisting of pH, color properties (CIE L(*), a(*), b(*), and total color difference, DeltaE), oxidative changes (thiobarbituric acid value and hexanal content) and bacterial counts (total viable cell, coliform, lactic acid bacteria, Enterobacteriaceae, Pseudomonas spp.) Initial meat pH was 6.16 and declined slightly during storage. TBA values and hexanal content were highest in O2 and lowest (P?0.05) in VAC and N2 atmospheres. Surface lightness (L(*)) and redness (a(*)) were highest in O2 packaging initially, decreasing (P?0.05) by day 9. DeltaE of the ground ostrich increased during storage in only O(2) and AIR packaging. All packaging methods had generally similar effects on microbial outgrowth. Total aerobic bacteria attained >10(6) CFU/g meat between day 3 and day 6. Ground ostrich meat was below saleable quality in less than 6 days based on all of the meat attributes. For O2 packaging however, quality based on lipid oxidation and color properties indicated a shelf-life of less than 3 days. Oxidation is likely the limiting factor for shelf-life of ground ostrich meat. PMID- 22062491 TI - Measurement of lipid oxidation and porphyrins in high oxygen modified atmosphere and vacuum-packed minced turkey and pork meat by fluorescence spectra and images. AB - This paper illustrates that fluorescence spectroscopy and imaging can be used to measure the extent and distribution of lipid oxidation in meat. Minced turkey thighs and pork semimembranosus muscles were stored for 7 and 12 days at 4 degrees C in high oxygen (O(2)) modified atmosphere packages and vacuum. Turkey meat packed in high O(2) atmosphere was oxidised already after 7 days of storage. The sensory rancid odour score was 4.7 (on a scale from 1 to 9) and the TBARS value was 1.86mg MDA/kg. There was also an increase in fluorescence emission intensity in the 410-550nm region, which arises from lipid oxidation products. The combination of unsaturated fatty acids and access to O(2) resulted in lipid oxidation gradients in the turkey meat samples, and these gradients were clearly visualised by fluorescence images. In comparison, pork meat was more stable against lipid oxidation, with TBARS values <0.2mg MDA/kg and no development of fluorescent lipid oxidation products was detected. The fluorescence spectra measured in the present experiment suggest that turkey thighs and pork semimembranosus muscle in addition to protoporphyrin also have a natural content of Zn protoporphyrin. The porphyrin content was higher in pork meat than in turkey meat. It increased during storage time when the meat was packed in vacuum, and it decreased with O(2) availability. The distribution of porphyrins in the meat was visualised by fluorescence imaging. PMID- 22062492 TI - Interlaboratory evaluation of dry-cured hams (from France and Spain) by assessors from two different nationalities. AB - Two panels of assessors from France and Spain assessed 41 dry-cured hams from diverse geographical origins, pig breedings and feedings. Univariate (Kolmogorov Smirnov test and t-test) and multivariate (canonical correlation and principal component analysis) statistical procedures have been used to explain the agreement and disagreement between panels evaluating similar and dissimilar sensory attributes quantified with a 9-points structure scale. The results pointed out that there were basic agreements between panels, although some disagreements were detected in mould, acorn and crust attributes. The classification of Iberian and white dry-cured hams and the sensory attributes that characterise them are also displayed. PMID- 22062493 TI - Effect of replacing soybean meal by extruded chickpeas in the diets of growing finishing pigs on meat quality. AB - The main objective of this study was to evaluate the effect of the replacement of soybean meal by extruded chickpeas in diets of growing-finishing pigs on meat quality. In a 17wk study 48 growing-finishing crossbred pigs were fed ad libitum. The experimental design included four treatments, each one of 12 pigs; the ECKP0 treatment was fed with diet containing soybean meal and no chickpeas (control), while treatments ECKP100, ECKP200 and ECKP300 were fed with diets containing 100, 200 and 300kg/t of extruded chickpeas, respectively. The lean meat quality of the longissimus lumborum et thoracis muscle was evaluated by chemical analysis (moisture, protein, fat and ash), fatty acid profile, pH measurement, cooking loss, color evaluation, and sensory evaluation. Odor and taste, tenderness, juiciness, and overall acceptability were scored on 1-10 scales by a group of 10 experienced assessors after a standard cooking regime. Small differences were observed between control and experimental groups in chemical composition (P>0.05). Fatty acid profiles, pH measurements and color evaluation did not differ among treatments (P>0.05), while cooking loss was significantly lower in the control group (P<0.05). The taste panel gave slightly higher scores for the tenderness and juiciness for the control group compared with the chickpea treatments (P<0.05). No differences were observed between control and experimental groups in taste scores (P>0.05). It is concluded that the replacement of soybean meal by extruded chickpeas, when substituted isonitrogenously and isoenergetically at inclusion levels up to 300kg/t of pig, does not influence significantly meat quality. PMID- 22062494 TI - Chemical oxidation decreases proteolytic susceptibility of skeletal muscle myofibrillar proteins. AB - The objective of this study was to investigate the effect of chemical oxidation on proteolysis susceptibility of myofibrillar proteins. Myofibrils were prepared from pig M. longissimus dorsi and oxidised by a hydroxyl radical generating system. Protein oxidation level was measured by the carbonyl content, free thiol group content and bityrosine formation. Oxidised or non-oxidised myofibrillar proteins were exposed to papain and proteolysis was estimated by fluorescence using fluorescamine. Oxidation of myofibrillar proteins was dependent upon the oxidising agent concentration. Disulfide bridge and bityrosine formation indicated that oxidation by OH degrees can induce protein polymerization. Electrophoretic study showed that myosin was the protein most sensitive to oxidation. Results showed a direct and quantitative relationship between protein damages by hydroxyl radical and decreased proteolytic susceptibility. Electrophoretic observations suggest that polymerization and aggregation may explain in part decreased susceptibility of myofibrillar proteins to proteolysis. PMID- 22062495 TI - Adherence with the pre-hospital triage protocol in the transport of injured patients in an urban setting. AB - BACKGROUND: Pre-hospital triage protocols are an important component in the treatment of injured patients. The aim was to determine the level of, and factors associated with, adherence to the pre-hospital trauma triage criteria for urban patients transported in New South Wales, Australia. METHOD: This retrospective study included patients injured in urban areas who were transported by road for the treatment of traumatic injuries in the period 1 July 2006 to 30 June 2007. RESULTS: Of the 57,775 transported to hospital due to traumatic injury, 9344 (16%) met one or more of the pre-hospital triage criteria. Of these, 74% were transported to a protocol adherent major or regional trauma centre. Adherence rates differed by triage criteria met and was lowest for patients meeting physiologic-only criteria (63.5%) and highest for patients meeting all three triage criteria of physiology, mechanism and injury (85.4%). Female gender, increasing patient age, patients classified as having had a fall, the qualification level of treating officer and patients transported between midday to 18:00 (relative to those transported between midnight to 06:00) were factors associated with significantly lower levels of protocol adherence with respect to hospital destination. Minimal time differences were evident between patients transported to protocol adherent and non-adherent destinations. CONCLUSION: Based on the post hoc evaluation of triage status, adherence to the triage protocol was 74%. Analysis of patient destinations for protocol non-adherence appears to indicate that paramedic interpretation and discretion played a role in determining hospital choice. There was a marginal time difference between those transported to protocol adherent and non-adherent destinations. Future research needs to determine whether deviations from protocol are associated with differential mortality. PMID- 22062496 TI - New pets and allergies. AB - This review focuses on the various symptoms of allergy induced by new pets, the new pets themselves, and some of the identified allergens. PMID- 22062497 TI - Interleukin-6 trans-signaling in the senescent mouse brain is involved in infection-related deficits in contextual fear conditioning. AB - Excessive production of pro-inflammatory cytokines in the senescent brain in response to peripheral immune stimulation is thought to induce behavioral pathology, however, few studies have examined if the increase in pro-inflammatory cytokines is accompanied by an increase in cytokine signaling. Here, we focused on IL-6 as a prototypic pro-inflammatory cytokine and used phosphorylated STAT3 as a marker of IL-6 signaling. In an initial study, IL-6 mRNA and the magnitude and duration of STAT3 activation were increased in the hippocampus of senescent mice compared to adults after i.p. injection of LPS. The LPS-induced increase in STAT3 activity was ablated in aged IL-6(-/-) mice, suggesting IL-6 is a key driver of STAT3 activity in the aged brain. To determine if IL-6 activated the classical or trans-signaling pathway, before receiving LPS i.p., aged mice were injected ICV with sgp130, an antagonist of the trans-signaling pathway. Importantly, the LPS-induced increases in both IL-6 and STAT3 activity in the hippocampus were inhibited by sgp130. To assess hippocampal function, aged mice were injected ICV with sgp130 and i.p. with LPS immediately after the acquisition phase of contextual fear conditioning, and immobility was assessed in the retention phase 48h later. LPS reduced immobility in aged mice, indicating immune activation interfered with memory consolidation. However, sgp130 blocked the deficits in contextual fear conditioning caused by LPS. Taken together, the results suggest IL-6 trans-signaling is increased in the senescent brain following peripheral LPS challenge and that sgp130 may protect against infection related neuroinflammation and cognitive dysfunction in the aged. PMID- 22062498 TI - Vulnerability, distress, and immune response to vaccination in older adults. AB - Psychological distress and biobehavioral vulnerability (e.g., arising from being older or sedentary) have independently predicted immune responses to influenza vaccination in older adults. Recent research examining basal inflammatory markers suggests that, rather than having additive effects, distress and vulnerability interact with each other. The present study tested the interactions between distress and age, sex, education, BMI, sleep quality, and physical activity over up to 8 years in older adults (N=134; M age=74 years) who received annual influenza vaccinations. Measured vaccination responses were changes from baseline in antibody to the three vaccine components, interleukin (IL)-6, and beta2 microglobulin. As predicted, the most robust effects were interactions between distress and vulnerability. BMI interacted with stable individual differences in distress to predict antibody response (t(132)=3.09, p<0.003), such that only the combination of low BMI and low distress was associated with a more robust antibody response. Likewise, changes in physical activity over time interacted with changes in distress (t(156)=2.96, p<0.004), such that only the combination of increased physical activity and decreased distress was associated with a more robust antibody response. Finally, there was a smaller tendency for age to interact with stable individual differences in distress (t(130)=2.46, p<0.015), such that distress was more strongly associated with post-vaccination IL-6 at older ages. The synergistic effects of distress and other forms of vulnerability are an important direction for future research and a target for interventions to improve immunological health in older adults. PMID- 22062499 TI - Twenty-five years of "Meat Science". PMID- 22062500 TI - Healthier meat and meat products: their role as functional foods. AB - This review deals with the implications of meat and meat products for human health. It analyses the effect of the presence or absence of various factors: fat, fatty acid composition, cholesterol, calorific value, salt, nitrite or lipid oxidation products that can cause health problems. Bearing in mind these considerations, it then describes the strategies used in animal production, treatment of meat raw material and reformulation of meat products to obtain healthier meat and meat products. Functional ingredients are responsible for making functional foods work, and this review therefore discusses the scope of current meat technology to favour the presence of various active-food components, and provide an additional physiological benefit beyond that of meeting basic nutritional needs. PMID- 22062501 TI - Lipolytic and proteolytic properties of dry-cured boneless hams ripened in modified atmospheres. AB - We studied proteolytic and lipolytic properties of dry-cured boneless ham (porcine quadriceps femoris) made with chilled (10 degrees C, 48 h) or frozen/thawed meat (frozen at -20 degrees C frozen for 90 days and followed by thawing at 10 degrees C for 48 h) were determined. Dry-cured meats were stored in modified atmosphere packages (100% N(2) and a mixture of 75% N(2)+25% CO(2)) at 15 degrees C with the intention of reducing ripening space. Results showed that dry-cured hams made with frozen/thawed raw meat had more salt, volatile fatty acids and free fatty acid content after salting and smoking. Whereas, samples prepared with chilled meats contained more nitrogenous compounds (water-soluble nitrogen, non-protein nitrogen, and free amino acids). Volatile and free fatty acid contents in all samples significantly increased with storage. Acetic acid was the predominant volatile fatty acid. To confirm lipolytic activity in dry cured ham stored in modified atmospheres, we calculated the lipolytic coefficient. The lipolytic coefficients of all samples were positive values and significantly (P<0.05) increased with storage indicating lipolysis in samples were still active. Furthermore, nitrogenous compounds in dry-cured ham significantly (P<0.05) increased with storage indicating proteolysis in samples were not affected by modified atmosphere storage. Aerobic, anaerobic and lactic acid bacteria counts in dry-cured meats were stable to modified atmospheres storage for 20 weeks at 15 degrees C. Flavor, texture and color score in sensory evaluation for dry-cured ham made with chilled meat were significantly higher than that made with frozen/thawed meat. All samples had high overall acceptance scores in sensory evaluation. Results in this study suggested that dry-cured boneless ham stored in modified atmospheres for 20 weeks at 15 degrees C was another feasibility to ripen the meat without affecting lipolysis, proteolysis, microbiology and sensory quality. PMID- 22062502 TI - Colour of beef heated to different temperatures as related to meat ageing. AB - The effects of ageing (10-12 days at +5 degrees C), thermal treatment (internal temperature, T(i): 45, 60, 75 degrees C) and oxygenation on the colour and some colour related physical and biochemical parameters of beef longissimus dorsi (LD) muscle were studied. The colour components (L(*), a(*) and b(*) values) for the raw and heated LD, both before and after ageing and oxygenation, were instrumentally and sensorily evaluated. Ageing influenced colour components (except b(*) value), specific activity of cytochrome c oxidase (SACCO) and amount of oxygen consumed (AOC). An increase in internal temperature was usually accompanied by a lower SACCO, AOC and total native muscle pigment concentration, as well as a change in all colour parameters. Oxygenation of the raw and heated slices (except T(i)=75 degrees C) led to a less of black colour and a higher of red colour, a(*) and b(*) values. PMID- 22062503 TI - Very fast chilling of beef: effects on meat quality. AB - The effect of very fast chilling (VFC) of beef on several meat quality parameters was studied in semitendinous samples of three young bulls of the Belgian Blue breed. Left carcass sides were chilled conventionally. The semitendinosus of the right carcass sides were hot boned at approximately 50 min post mortem and cut longitudinally in two equal pieces. Packed in plastic bags, one piece was chilled very fast using a brine solution (3.4% NaCl, -2 degrees C), whereas the other was chilled in a freezer (-20/-25 degrees C, 3 m/s). The very fast chilling treatments lasted until 5 h post mortem. Samples were further chilled in a refrigerator (2 degrees C) until 24 h post mortem. Sub-samples for meat quality measurements were taken and frozen at -18 degrees C after an ageing period of 1, 4 and 11 days at 2 degrees C. In three of the six cases, a core temperature of 0 degrees C was achieved within 5 h post mortem [VFC condition; In the other cases, the VFC condition was nearly met. The brine chilling treatment in this study resulted in a higher cooling rate compared with the freezer treatment, and concomitantly in more pronounced effects. VFC resulted in increased concentrations of water extractable calcium and higher pH values at 5 h post mortem. These factors could be expected to activate the calpains and to accelerate proteolysis. This could not be confirmed by our results. Cold shortening occurred and sarcomere lengths were reduced by more than 30% in the VFC treatment compared with conventional chilling. This was reflected in much higher shear force values for the VFC samples. PMID- 22062504 TI - Oxidative stability and fatty acid composition of pig muscles as affected by rearing system, crossbreeding and metabolic type of muscle fibre. AB - Muscle fibre type, fatty acid composition of phospholipids (PLs) and triacylglycerols (TGs) and susceptibility of muscle to lipid oxidation were studied in Biceps femoris (BF) and Tibialis cranialis (TC) muscles from Iberian and Iberian*Duroc pigs reared indoors and outdoors. Fatty acid composition of TGs was not affected by muscle fibre type and crossbreeding, but was strongly influenced by rearing system. In PLs crossbreeding slightly affected monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) content in BF muscle, whereas rearing system showed a great influence on fatty acid composition of PLs. Oxidative fibres showed a positive relationship with saturated fatty acid (SFA) and MUFA contents and a negative one with PUFA content of PLs. Susceptibility of muscle to lipid oxidation was strongly influenced by diet, animals reared indoors and fed on concentrates showing higher levels of 2 thiobarbituric acid reactive substances (TBARS). Iberian*Duroc pigs tended to show slightly higher values of lipid oxidation than pure Iberian pigs. With regards to muscle fibre type, BF had lower TBARS values than TC, although within muscle no relationship was found between muscle fibre type and lipid oxidation. PMID- 22062505 TI - Relationships between muscle characteristics and meat quality traits of young Charolais bulls. AB - Charolais bull calves (106) were used to study the variability in meat quality attributes in relation to the variability in muscle characteristics in the Longissimus thoracis (LT) muscle. The variability in traits was adjusted either to constant age or constant weight at slaughter and thus originated only from differences between animals born, reared and fattened in the same location. The following meat quality attributes were measured: the strength of the myofibrillar resistance to a 20% compression strain measured on the raw meat 2, 7 and 21 days post mortem; and taste panel scores of tenderness (initial and overall), flavour and juiciness of steaks grilled to a 55 degrees C core temperature 6 or 15 days post-mortem. The following muscle characteristics were measured 24 h after slaughter: pH, dry matter, protein, lipid, heme iron and collagen contents, collagen solubility, LDH and ICDH activity, the proportion of slow twitch myosin heavy chain, the mean muscle fibre area and the mean sarcomere length. One fourth to one third of the variability of 2 day mechanical strength and 15 day tenderness or flavour scores were related to the variability in muscle characteristics. Tenderness and strength measurements were predominantly related to the muscle fibre area, collagen characteristics and energetic metabolic activity. Dry matter content was the principal muscle characteristic related to flavour. PMID- 22062506 TI - Characterization of peptides released from rabbit skeletal muscle troponin-T by MU-calpain under conditions of low temperature and high ionic strength. AB - Rabbit skeletal muscle troponin-T (200 MUg ml(-1)) was incubated with MU-calpain (2 MUl ml(-1)) under conditions of low temperature and high ionic strength for 180 min at 4 degrees C and the peptides released analyzed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Troponin-T was hydrolyzed rapidly with the simultaneous appearance of eight peptides with masses of less than 14 up to 26 kDa. Two peptides produced by 10 min of incubation were electroblotted and analysis of these peptides by N-terminal sequencing and mass spectrometry showed that the principal cleavage sites of MU-calpain on troponin-T were at Thr(45)-Ala(46), Leu(69)-Met(70), Glu(220)-Lys(221) and Asn(231) Val(232). The peptides present in insufficient quantity for electroblotting were isolated by reverse-phase high performance liquid chromatography (RP-HPLC). Cleavage sites were also identified at Met(151)-Gly(152), Asn(188)-Ile(189), Lys(223)-Arg(224), Arg(233)-Ala(234) and Ala(240)-Lys(241). In general, MU calpain cleaved bonds containing one hydrophobic amino acid residue and mainly towards the C-terminus of troponin-T. PMID- 22062507 TI - Quality changes and shelf life of imported vacuum-packaged beef chuck during storage at 0 degrees C. AB - Twenty-four beef chucks obtained from US steer carcasses were placed in cartons after vacuum packaging in gas tight film. These were then transported by refrigerated ship to Korea. After arrival at laboratory (37 days after packaging), the cuts were stored at 0 degrees C additionally for 39 days and analyzed. After 52 days of storage total aerobic counts exceeded 7 log(10)CFU/cm(2), however, Enterobacteriaceae and Pseudomonas showed growth retardation. Brochothrix thermosphacta was not found at the level of 2 log(10)CFU/cm(2) over the storage time. Among the biogenic amines, the concentration of spermine was notably increased initially from 8.5 to 25 ppm after 76 days. At day 76 of storage, the colour deterioration with respects to a and hue values was pronounced after opening the vacuum pack. Off-odour was detected after 66 days of storage. PMID- 22062508 TI - Inhibition of the proliferation of myeloma cells by the meat origin strain Enterococcus faecium CH3. AB - Ten lactic acid bacteria strains were isolated from a dry fermented sausage and tested for stimulation or inhibition of the proliferation of Vero and myeloma cells by MTT assay. None of the strains significantly affected the proliferation of Vero cells. However, one isolate (CH3) showed a strong inhibition of myeloma cells proliferation. Isolate CH3 was submitted to a characterisation scheme and identified as Enterococcus faecium by SDS-PAGE protein profiling and DNA sequencing of 16S rRNA PCR products. PMID- 22062509 TI - Microbial and physico-chemical changes during the ripening of dry fermented sausages superficially inoculated with or having added an intracellular cell-free extract of Penicillium aurantiogriseum. AB - The effect of inoculation of the "salchichon" (dry fermented sausage) surface with an atoxygenic, proteolytic and lipolytic strain of Penicillium aurantiogriseum and/or the addition of an intracellular cell-free-extract (ICFE) of the same mould on the ripening process was studied. Four batches of salchichon were manufactured: control, superficially inoculated, added with the intracellular cell free extract and combination of both treatments. Superficial mould modified Micrococcaceae counts, pH, free amino acids, lipid fractions, TBARS and some organic acids. The ICFE degraded free amino acids, producing a rise in ammonia. Both treatments combined accelerate the proteolysis and lipolysis of the sausages and also the further amino acid degradation. PMID- 22062510 TI - The contribution of Penicillium aurantiogriseum to the volatile composition and sensory quality of dry fermented sausages. AB - An atoxygenic, proteolytic and lipolytic strain of Penicillium aurantiogriseum was tested for its ability to accelerate the production of volatile compounds and to improve the sensory properties of dry fermented sausages. The following batches of sausages were prepared: control; superficially inoculated with a spore suspension; added with an intracellular cell free extract; and superficially inoculated and added with the intracellular cell free extract. Higher levels of lipid oxidation products were found in the aroma extracts of sausages without a mould cover. In contrast, branched aldehydes and alcohols presented higher concentrations in superficially inoculated and extract added sausages, while esters only showed higher concentration in the first ones. The sensory analysis showed that sausages prepared with both treatments received the highest scores in all the properties evaluated, which demonstrated both the potential of this mould as producer of volatile compounds and the effectiveness of combining both treatments. PMID- 22062511 TI - Effects of urea denatureation and pH on the ability of porcine myoglobin to undergo reduction. AB - To determine the effects of globin moiety denaturation and pH on the ability of metmyoglobin (MetMb) to undergo reduction, MetMb isolated from porcine hearts was denatured in 8.5M urea. Both native and denatured MetMb solutions were serially reduced with Na(2)S(2)O(4) (0, 7.5, 15, 18.75, 22.5, 26.25, 30, 30.75, and 45 umol). Reduction was conducted at pH 5, 5.2, 5.4, 5.6, 6, 6.2, 6.4, 6.6, and 7. After reduction, absorbance was determined at 635 nm and the percent of the original MetMb which was reduced was calculated. The average percent MetMb reduced from the native and denatured forms was 35 and 25%, respectively. pH significantly influenced the percentage of MetMb reduced, especially when pH was <6. If the MetMb was denatured prior to reduction, the influence of pH on its ability to undergo reduction was slight. The percentage of denatured MetMb reduced was higher at pH 7 than at all other pHs. High pH enhanced the ability of MetMb to undergo reduction; while low pH decreases it. Low pH may have denatured the native globin moiety. PMID- 22062512 TI - Combined effects of irradiation and the use of natural antioxidants on the shelf life stability of overwrapped minced beef. AB - Five batches of aerobically packaged minced beef from Friesian cattle were irradiated at 0, 1, 2, 3 or 4 kGy using a (60)Co irradiation source. The five batches were as follows: non-supplemented (C), dietary alpha-tocopheryl acetate supplemented (S), alpha-tocopheryl acetate supplemented with water soluble rosemary extract added after mincing (Rw), alpha-tocopheryl acetate supplemented with oil soluble rosemary extract added after mincing (Ro) and alpha-tocopheryl acetate supplemented with water and oil soluble rosemary extracts added after mincing (R). Incorporation of antioxidants resulted in better retention of colour. Irradiation at 4 kGy increased Hunter 'a' values up to day 4 with alpha tocopheryl acetate supplementation and up to day 6 when rosemary extracts were added. Irradiation at 4 kGy increased Hunter 'b' values on days 4, 6 and 8 in the control samples. Antioxidants decreased metmyoglobin values on day 0 and day 2 for non-irradiated (0 kGy) samples and for the entire display period for irradiated samples. Antioxidants increased the oxymyoglobin values up to day 4 for the 1, 2 and 3 kGy beef samples and over the entire display period for the 4 kGy samples. TBARS values for each treatment group increased with increasing irradiation dose. alpha-Tocopheryl acetate supplemented samples had lower TBARS values than control samples at all irradiation doses. The levels of alpha tocopherol in samples on day 0 decreased with increasing irradiation dose for the (C) and (S) samples. However, levels of alpha-tocopherol in samples on day 0 increased with increasing irradiation dose for Ro, Rw and R samples. All antioxidant treatments were effective at inhibiting lipid peroxidation even at the highest irradiation dose applied. Irradiation caused a significant reduction in the polyunsaturated fatty acid (PUFA) content, mainly in C18:2 after storage at 40 degrees C under fluorescent light for 8 days. PMID- 22062513 TI - Chemical and discriminant analysis of bovine meat by near infrared reflectance spectroscopy (NIRS). AB - Near infrared reflectance spectroscopy (NIRS) was evaluated as a tool to segregate different types of bovine meat and predict several chemical fractions on samples from two breeds, three muscles and six grading (Chilean system) categories. Samples previously minced, frozen and thawed, were scanned (400-2500 nm) and then analyzed for dry matter, crude protein, ether extract, total ash and collagen content, after freeze drying. Discriminant analysis using a partial least squares regression technique and cross validation, correctly identified breed and muscle type for most samples, but carcass grades, with the exception of samples from calves, were not successfully predicted. Best calibrations for chemical composition tested by cross-validation, showed R(2) and standard errors of cross validation of 0.77 and 0.58% (dry matter), 0.82 and 0.48% (crude protein), 0.82 and 0.44% (ether extract). Calibrations for total ash showed a poor, and for collagen, a very poor prediction ability. PMID- 22062514 TI - A novel approach to grading pork carcasses: computer vision and ultrasound. AB - A Computer Vision System prototype for grading pork carcasses was developed at the Lacombe Research System. The system consists of two components: ultrasound imaging to scan a cross-section of the loin muscle and video imaging to capture two-dimensional (2D) and three-dimensional (3D) images of the carcass. For each of the 241 carcasses (114 barrows and 127 gilts), salable meat yield was determined from a full cutout. Linear, two- and three-dimensional, angular and curvature measurements and carcass volume were derived from each image. Muscle area and fat thickness (7 cm off the mid-line) measured by ultrasound at the next to last rib site, together with 2D and 3D measurements provided the most accurate model for estimating salable meat yield (R(2)=0.82 and RSD=1.68). Models incorporating fat thickness and muscle depth measured at the Canadian grading site (3/4 last rib, 7 cm off the mid-line) with the Destron PG-100 probe, had the lowest R(2) and highest residual standard deviation (RSD) values (R(2)=0.66 and RSD=2.15). Cross-validation demonstrated the reliability and stability of the models; hence conferring them good industry applicability. The Lacombe Computer Vision System prototype appears to offer a marked improvement over probes currently used by the Canadian pork industry. PMID- 22062515 TI - Ellipsometry across isolated muscle fibres indicates a refractive contribution to paleness in pork. AB - Muscle fibres isolated from pork were mounted in a microscope chamber and pH was controlled with 0.2 M phosphate buffer. Optical path differences between ordinary and extraordinary rays were measured by ellipsometry while a scanning stage moved the fibre across the optical axis of the microscope. The depth of fibre in the optical axis was estimated from the lateral diameter of fibres. Path differences increased as fibre depth increased. Static ellipsometry of unmounted fibre fragments showed maximum path differences at pH 5.5 were higher than at pH 7.0, but variance was high and the difference was not significant (64.4+/-15.1 nm at pH 5.5 versus 58.9+/-15.2 nm at pH 7.0, P>0.05, n=40). However, the mean depth of fibre fragments at pH 5.5 was less than at pH 7.0 (53.9+/-15.1 MUm at pH 5.5 versus 70.6+/-16.1 MUm at pH 7.0, P<0.005, n=40). Thus, path differences per micrometre of fibre depth were greater at pH 5.5 than at pH 7.0 (1.25+/-0.37 nm( 1 MUm) at pH 5.5 versus 0.87+/-0.31 nm(-1 MUm) at pH 7.0, P<0.0005, n=40). As pH decreases, therefore, muscle fibre diameter decreases while birefringence increases. Refraction through muscle fibres may contribute to pork paleness. PMID- 22062516 TI - Drip loss sampling in porcine m. longissimus dorsi. AB - The effect of the sampling position is investigated when measuring drip loss in porcine longissimus dorsi muscle. Measuring in biological tissue often includes an assumption of homogeneity of the muscle under investigation, an assumption that only applies to a certain extent. However, this assumption is particularly critical when measuring drip loss. In the present experiment two different methods for measuring drip loss were applied. The two methods use a considerably different sample size and thus a difference in sensitivity to the heterogeneity of the object to be measured may be expected. In other words, when measuring drip loss a large sample size may blur information about biological variations in the parameter under investigation. The influence of the sampling position on the drip loss measurement 34 pigs were selected from a random group of 204 pigs. The right and the left longissimus dorsi were excised and used as objects for measuring drip loss with two different methods. Each longissimus dorsi muscle was sliced in 11-15 slices of 2.5 cm thickness. The left longissimus dorsi was sampled in three positions for each slice and the drip loss was measured in each position applying the EZ-DripLoss method. The longissimus dorsi from the right side of the carcasses was measured with the bag method. Our measurements showed a substantial variation in the influence of the sampling position on the result of determination of drip loss. The influence is calculated as the standard deviation (SD) between measurements performed in different positions in transverse and longitudinal direction along the longissimus dorsi muscle. Our work showed that the optimum position of sampling for drip loss determination was 5 cm cranial to the start of the fourth lumbar vertebra, where we found a SD between neighbouring sampling positions of less than 0.74%. We found a high correlation (0.85) between the methods applied even though this value included differences between the right and the left side of the carcass. From one single measurement of drip loss performed on the left longissimus dorsi with the EZ-DripLoss method, we were able to predict the average drip loss of the right longissimus dorsi with a very high correlation (>0.9). We are still searching for an explanation for the 1.2% offset between the two methods employed in this experiment. PMID- 22062517 TI - Behaviour of Listeria monocytogenes in raw sausages (merguez) in presence of a bacteriocin-producing lactococcal strain as a protective culture. AB - The effectiveness of a bacteriocin produced by Lactococcus lactis subsp. lactis M in reducing population level and growth of Listeria monocytogenes ATCC 7644 in fermented merguez sausage was examined. Two different formulas (with or without added nitrites) were assayed and predetermined numbers of Listeria (ca 10(6) cfu g(-1)) were added to sausage mixture. The effect of in situ production of the bacteriocin by Lactococcus lactis M on Listeria monocytogenes ATCC 7644 during fermentation and storage of merguez sausages at room (ca 22 degrees C) or at refrigeration (ca 7 degrees C) temperature was tested. Results indicated that counts of Listeria monocytogenes were decreased during fermentation of merguez samples fermented with either the bacteriocin-producing Lactococcus lactis M (Bac(+)) or a nonbacteriocin-producing Lactococcus lactis J (Bac(-)). However, reduction in Listeria cfu's was greater in samples fermented with the Bac(+) than in those fermented with the Bac(-) starter. In merguez sausage made without nitrites addition, the Bac(+) starter induced further decrease in Listeria counts by 1.5 log cycles compared with that induced by the Bac(-) starter. While in merguez samples with added nitrites (0.4%), the effect of the bacteriocin produced in situ was less important than in those made without nitrites addition. PMID- 22062518 TI - Cured products from different animal species. AB - An assessment was made of the proximate composition, pH and a(W) of raw beef, horsemeat and the meat of wild boar, deer and goat. The same assessment, together with one of fatty acids, cholesterol and free amino acids, was made of the same meats as cured products. The raw meat of the different animal species was found to have a reduced lipid, but high protein content. The cured meat of the horse and wild boar had low saturated fatty acid levels; the wild boar, goatmeat and beef were quantitatively similar with regard to monounsaturated fatty acids (MUFA) while in the horsemeat the polyunsaturated fatty acids (PUFA) were more raised, at an intermediate level in deer and extremely reduced in the beef final product. The cholesterol content in the cured product was markedly reduced in the horsemeat. The free amino acids content in the cured deer, wild boar and goat meat was more elevated, than in beef and horse cured meat. PMID- 22062519 TI - Meat quality of Angus, Simmental, Charolais and Limousin steers compared at the same intramuscular fat content. AB - Meat quality and marbling properties of Angus, Simmental, Charolais and Limousin steers (4*16) were compared at an average intramuscular fat content (IMF) of 3.25% in the M. longissimus dorsi. The steers were fattened on a forage-based diet until the desired, ultrasonically estimated IMF content was reached which resulted in considerably different growth and carcass characteristics. The Angus group showed a growth rate similar to Simmental and Charolais while Limousin grew slower, became oldest and provided the heaviest carcasses and best conformation. Angus carcasses showed the lowest weight but the highest fatness score. Marbling was equal for all breeds. Angus and Charolais provided pale meat with low haem iron content. Angus and Limousin beef was more tender on sensory assessment than Simmental beef, corresponding to differences found in shear force (non significant) and myofibrillar fragmentation index measured at 48 h post mortem. Flavour was similar among breed groups while juiciness was highest for Limousin and lowest for Angus. The juicier beef simultaneously showed the highest drip but the lowest cooking losses. In conclusion, clear differences in meat quality were observed between breeds despite similar IMF contents. PMID- 22062520 TI - Effects of lactic and acetic acid salts on quality characteristics of enhanced pork during retail display. AB - The objective of this study was to evaluate the sensory and physical characteristics of pork chops from loins enhanced to 110% of original weight with either (1) potassium lactate, potassium diacetate, phosphate and salt, (2) sodium lactate, phosphate and salt, (3) potassium lactate, phosphate and salt, (4) sodium acetate, phosphate and salt, or (5) phosphate and salt. A trained sensory panel evaluated pork flavor, saltiness, bitterness, soapy flavor, acid flavor, juiciness and tenderness of cooked chops. Visual color of raw chops was also evaluated. After 96 h in display, chops enhanced with lactate/diacetate had significantly lower (P<0.01) aerobic plate counts than control (unpumped) chops, or those pumped with other solutions. Lactate/diacetate-enhanced chops maintained higher a* and b* values during display, and had less visual discoloration after 96 h display. Chops pumped with lactate, acetate or the lactate/diacetate mixture were more tender and juicy, and had more pork flavor than controls or those pumped with phosphate/salt only. There appears to be a significant advantage to using a lactate/diacetate enhancement solution over either lactate or acetate alone. PMID- 22062521 TI - Effect of season on color of Hanwoo (Korean native cattle) beef. AB - A total of 1278 head of Hanwoo (Korean native cattle) slaughtered over four seasons were used to evaluate the effect of season on color characteristics of beef longissimus dorsi (LD) muscle. CIE L(*), a(*), b(*), C(*) values and hue angle were significantly lower (P<0.05) in cattle slaughtered in the winter season. Meat color was darker in the winter than in the spring and autumn seasons. The L(*) values among three average daily temperature (T(a)) categories were different (P<0.05) in order of: [5 degrees C?T(a)<25 degrees C] > [T(a)?25 degrees C] > [T(a)<5 degrees C], indicating that the meat color of cattle slaughtered at T(a)<5 degrees C was darker. The a(*), b(*), C(*) values and hue angle were significantly lower (P<0.05) in cattle slaughtered at T(a)<5 degrees C. Season at slaughter is of great importance for meat color. Namely, meat color of Hanwoo beef was influenced by environmental temperature. Overall, cattle slaughtered in the winter season of T(a)<5 degrees C produced beef with more undesirable meat color properties. PMID- 22062522 TI - On-line prediction of chemical composition of semi-frozen ground beef by non invasive NIR spectroscopy. AB - The chemical composition of industrial scale batches of frozen beef was measured on-line during grinding by near infrared (NIR) reflectance spectroscopy. The MM55E filter based non-contact NIR instrument was mounted at the outlet of a meat grinder, and the fat, moisture and protein contents determined from the average of each filter reading throughout the grinding of the batch. The filters were selected from full spectra measurements to be as insensitive to water crystallization as possible. For on-line calibration and prediction, 55 beef batches of 400-800 kg in the range of 7.66-22.91% fat, 59.36-71.48% moisture, and 17.04-20.76% protein, were ground through 4 or 13 mm hole plates. The regression results, presented as root mean square error of cross validation (RMSECV) were between 0.48 and 1.11% for fat, 0.43 and 0.97% for moisture and 0.41 and 0.47% for protein. PMID- 22062523 TI - Maintaining muscles at a high post-mortem temperature induces PSE-like meat in turkey. AB - The aim of the present study was to validate an experimental model which surely generates pale, soft, exudative (PSE) turkey meat. Immediately after exsanguination, Pectoralis major (n=15) were kept at various temperatures (4, 20 or 40 degrees C) for 6 h. All the muscles were then stored at 4 degrees C for 9 days. They had the same rate of pH fall. L(*) values were higher in the 40 degrees C treatment muscles than in the two other treatment muscles between 1 and 9 h. Drip loss of the 40 degrees C treatment muscles was higher than in the two other treatment muscles. However, thawing and cook loss were not significantly different between treatments. Cooked meat from the 40 degrees C treatment muscle was tougher than the two other treatment muscles. Napole yield was lower for these muscles. Myofibrillar protein extractability was lower in the 40 degrees C treatment muscle whatever the considered time. We showed that the 40 degrees C treatment muscles were similar to PSE muscles. PMID- 22062524 TI - Physicochemical characteristics of three muscles from free-range reared Iberian pigs slaughtered at 90 kg live weight. AB - Three muscles from free-range reared pigs with different metabolic pattern were studied. m. Masseter (M), m. Longissimus dorsi (LD) and m. Serratus ventralis (SV) the first having an oxidative metabolism and the other two an intermediate and glycolytic metabolism. m. Masseter contained the highest content of myoglobin (M: 6.65 mg/g, LD: 3.00 mg/g and SV: 3.64 mg/g; P<0.001) and exhibited the highest CIE a* (M:17.10, LD: 14.83, SV:15.34, P<0.001) and C* (M: 17.95, LD: 15.61, SV: 15.54, P<0.001) values. m. L. dorsi and S. ventralis contained a higher intramuscular fat content than m. Masseter (M: 2.26 g/100 g muscle, LD: 4.79 g/100 g muscle, SV: 3.52 g/100 g muscle, P=0.001) and lower amounts of phospholipids (M: 0.33 g/g imf, LD: 0.12 g/g imf, SV: 0.19 g/g imf; P<0.001). Fatty acid profiles from total intramuscular fat and lipid fractions, neutral lipids and polar lipids, significantly differed among muscles, there being a higher content of unsaturated fats (especially in the C18:2 and C20:4 percentages) in the m. Masseter than in the other two muscles analysed. Comparatively, muscles from 90 kg live weight Iberian pigs contained more fat and heme pigments and were redder than those from the commercial pig crosses usually produced. PMID- 22062526 TI - Color evaluation of carbon monoxide treated porcine blood. AB - The stability of liquid porcine blood, treated with carbon monoxide (CO) at different pH values (7.40, 6.70, and 6.00) up to its complete saturation, was studied. Lowering the pH from 7.40 to 6.70 resulted in a decrease in the amount of CO necessary to obtain 100% carboxyhemoglobin. Further pH lowering to 6.00 did not result in additional reduction in the amount of gas. During 4 days of refrigerated storage CO treated liquid blood maintained, at every pH, a more stable and attractive red color than fresh blood, which was a result of an increase (P<0.05) of a(*) (redness) and b(*) (yellowness) values and no variation (P>0.05) on L(*) (lightness) value. Hue (h(*)) and chroma (C(*)) decreased in the untreated blood but not in the CO-treated blood. The results indicate that blood saturation with CO yields a product having greater potential for use in meat products without compromising its visual appearance. PMID- 22062527 TI - Identification of myofibrillar substrates for MU-calpain. AB - To identify myofibrillar substrates of MU-calpain under post-mortem conditions, a combination of SDS-PAGE, two-dimensional gel electrophoresis (2DE) and matrix assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) was used. Purified myofibrils were incubated with MU-calpain under post mortem-simulated conditions for two or four days at 4 degrees C. The resulting protein changes were analyzed by SDS-PAGE and 2DE. The MU-calpain-mediated protein changes were identified by peptide-mass mapping using MALDI-TOF MS and revealed that desmin, actin, myosin heavy chain, myosin light chain I, troponin T, tropomyosin alpha1, tropomyosin alpha4, thioredoxin and CapZ are all degraded in vitro by MU-calpain. The findings that actin and myosin heavy chain are substrates of MU-calpain were rather surprising, as it has previously been reported that these proteins are resistant to MU-calpain degradation. However, both actin and myosin heavy chain are poor substrates compared with desmin. PMID- 22062528 TI - Comparison of the performances of Nero Siciliano pigs reared indoors and outdoors: 2. Joints composition, meat and fat traits. AB - A study on the effect of rearing system on tissue composition of principal joints and chemical-physical traits of meat and subcutaneous fat, was carried out on a local pig breed. A total of 78 Nero Siciliano pigs was used; 41 pigs were reared in woods, 37 pigs were reared in pens and fed a commercial diet. Weight at slaughter was 101.9 and 88.2 kg for indoor and outdoor pigs, respectively. Means were estimated at 77 kg of live weight. At ham dissection outdoor-pigs showed higher percentages of lean (58% vs. 55%) and lower subcutaneous fat (31% vs. 34%). In Longissimus lumborum outdoor-pigs showed a higher intramuscular fat percentage (4.3% vs. 3.3%), a lower protein content (22.2% vs. 23.4%), and higher free water (9.6 vs. 7.9 cm(2)). Outdoor pigs produced more light (L(*)=50 vs. 46.7) and more yellow (b(*)=5.84 vs. 4.88) meat. Subcutaneous fat of outdoor pigs showed higher percentages of MUFA (53.3% vs. 47.2%) and lower percentages of PUFA (10.85% vs. 14.45%), no differences were found for n-3 PUFA. Outdoor-pigs had lower atherogenicity (0.48 vs. 0.53) and thrombogenicity (1.03 vs. 1.21) indices. PMID- 22062529 TI - High voltage electrical stimulation enhances muscle tenderness, increases aging response, and improves muscle color from cabrito carcasses. AB - Our study examined high and low voltage electrical stimulation and postmortem storage as strategies to improve tenderness and lean color in cabrito carcasses. Boer cross (n=60) kids were assigned to either high (550 V), low (20 V), or no electrical stimulation treatments. No differences in muscle temperature were observed between treatments at any time measured. Muscle pH declined fastest in high voltage treated carcasses. High voltage electrical stimulation slightly increased (P<0.05) b (*) and a (*) in the M. gluteus medius and tended to increase L (*) and b (*) (P=0.06 and 0.11, respectively) values in the M. longissimus thoracis. Electrical stimulation had no effect on myofibril fragmentation at 1-, 3-, or 14-d postmortem or sarcomere length. High voltage electrical stimulation increased (P<0.05) tenderness at 1- and 3-d postmortem, but not at 14-d postmortem. Aging for 3 d did not affect tenderness regardless of stimulation treatment, but aging time for 14 d improved (P<0.05) tenderness. These data indicate that high voltage electrical stimulation and 14 d aging were effective in improving the tenderness of meat from cabrito carcasses. PMID- 22062530 TI - Evaluation of three ultrasound instruments, CVT-2, UltraFom 300 and AutoFom for predicting salable meat yield and weight of lean in the primals of pork carcasses. AB - Three commercially available ultrasound instruments were evaluated using pigs representative of the Canadian pig population: CVT-2, UltraFom 300 and AutoFom. The reflectance probe HGP2 was utilized as the baseline instrument. Sampling was stratified by fat thickness. The original data set (n=236) was divided randomly into a calibration set (n=194 [85 barrows and 109 gilts]) to calibrate the instruments and a validation set (n=72[32 barrows and 40 gilts]) for validating the calibration models. For salable meat yield, RMSE values for the calibration models were: HGP2, 1.56; CVT-2, 1.57; UltraFom, 1.70; and AutoFom, 1.68. For lean (kg) in butt, picnic, loin and ham, and weight (kg) of the skinless, trimmed belly, RMSE for the calibration models was similar for all four instruments: respectively, 0.19-0.21, 0.21-0.23, 0.31-0.37, 0.35-0.40 and 0.35-0.36 kg. Validation results for predicting salable meat yield show that the improvement in precision and/or accuracy associated with the UltraFom 300 or AutoFom, over the baseline reflectance probe HGP2, was negligible whereas a definite advantage was observed for the CVT-2. However, validation results for predicting kg of lean in the primals did not show any clear advantage for the three commerciallly available ultrasound instruments over the baseline reflectance probe HGP2. Calibration and validation procedures showed that, if one was to base the assessment of these three ultrsound instruments uniquely on the precision and accuracy for predicting salable meat yield and/or kg of lean in the primals, any amelioration over the baseline reflectance probe HGP2 would have to be viewed as rather negligible; particularly for the UltraFom 300 or AutoFom. PMID- 22062531 TI - Lipid and protein oxidation, release of iron from heme molecule and colour deterioration during refrigerated storage of liver pate. AB - In the present work, lipid and protein oxidation, increase of non-heme iron (NHI) content and colour changes occurring during refrigerated storage (90 days/4 degrees C) of liver pates from Iberian and white pigs were studied. Iberian pigs were reared outdoors and fed on natural resources (grass, acorns) while white pigs were intensively reared and fed on a mixed diet. Lipid and protein oxidation were, respectively, measured by determining TBA reactive substances (TBARS) and protein carbonyl groups. Pates from Iberian pigs had better oxidative stability at all stages of storage, having lower amounts of TBARS and carbonyls compared to those from white pigs (p<0.05). NHI increased during refrigerated storage of liver pates, with those from white pigs having a higher amount of NHI at all stages of storage (p<0.05). During refrigerated storage, L(*)-values tended to increase while the evolution of a(*) and b(*) depended on the group and did not seem to be related to the oxidative processes. PMID- 22062532 TI - The role of integrin degradation in post-mortem drip loss in pork. AB - Cell membranes are attached to the cell body by two major types of adhesion complexes, integrin-containing focal adhesions and the dystrophin/dystroglycan complex of proteins. In this study, we used samples with known and varying rates of drip channel formation to determine whether the time frame of formation of the channels correlated with the rate of cell/membrane adhesion protein degradation. Our results indicate that the degradation of the beta1-chain of integrin, the portion of the protein involved in adhesion of the cell membrane to the cytoskeleton, temporally correlates to the opening of drip channels in pork, while dystrophin degradation does not. Additionally, this degradation may be due to activation of calpains at the site of adhesion plaques. Previous work has indicated that calpains can degrade the beta-chain of integrins in vitro. We find that m-calpain is co-localized with beta1-integrin at the cytoplasmic surface of the cell membrane in plaque-like structures and is active in these regions post mortem. Inhibition of calpains not only results in inhibition of integrin degradation, but blocks the opening of drip channels. Therefore, the opening of drip channels in pork may well be due to the degradation of integrin proteins on the cell surface by calpains. PMID- 22062533 TI - Effect of muscular hypertrophy on physico-chemical, biochemical and texture traits of meat from yearling bulls. AB - The effect of the presence of the double-muscling gene either homozygous (mh/mh) or heterozygous (mh/+) on the physico-chemical, biochemical and texture traits of Longissimus thoracis muscle of yearling bulls of the Asturiana de los Valles (AV) breed was studied. Meat of mh/mh bulls had lower amount of intramuscular fat (p<0.001) and also lower total (p<0.01) and insoluble collagen (p<0.05), although the double-muscling genotype did not affect collagen solubility. Homozygous animals had lower pigment content (p<0.05) and a lighter meat, showing lower water holding capacity, estimated as expressible juice under pressure (p<0.001). Genotype affected significantly the metabolic traits of muscle, with mh/mh animals having higher muscle glycolytic metabolism, assessed by a higher (p<0.001) lactate dehydrogenase (LDH) activity and lower (p<0.001) oxidative activity of the isocitrate dehydrogenase (ICDH). The percentage of myosin heavy chain I in muscle was lower, although not significantly, for mh/mh bulls compared to mh/+ bulls. Texture measurements performed on raw material showed that meat of mh/mh bulls had lower resistance to total and 80% compression, which means lower background or collagen toughness. However, there were no differences between genotypes on shear force of cooked meat. Therefore, the physico-chemical, biochemical and texture traits of meat from mh/mh and mh/+ bull are in general significantly different, which could affect the sensorial quality of meat and hence the consumer acceptance. PMID- 22062534 TI - Optimizing colour quality of modified atmosphere packed sliced meat products by control of critical packaging parameters. AB - To study the influence of different packaging and storage parameters on the colour stability of modified atmosphere packed, cured, cooked ham, a multiplicative analysis of variance model (GEMANOVA) was developed. The critical parameters investigated were % residual-O(2), product to headspace volume ratio (P/H volume ratio), temperature, light intensity and oxygen transmission rate (OTR). The model illustrated that all the investigated parameters interacted, but especially % residual-O(2) and P/H volume ratio - i.e., the absolute O(2) content, influenced the degree of discoloration. The complex interactions of the parameters justified the selected model, as it emphasised the necessity of evaluating the parameters simultaneously instead of considering them individually. The importance of absolute O(2) content was further validated through an industrial experiment including three different kinds of sliced meat products. PMID- 22062535 TI - Influence of myosin heavy chain isoform expression and postmortem metabolism on the ATPase activity of muscle fibers. AB - The objective of this study was to determine the effects of postmortem muscle pH and temperature declines on the actomyosin ATPase activity of muscle fibers expressing different MyHC isoforms. Using a quantitative histochemical procedure to determine ATPase activity, the maximum actomyosin ATPase activity was determined on individual fibers classified by MyHC expression. Samples were collected from the red (RST) and white (WST) semitendinosus muscles at 3 min and 24 h postmortem from electrically stimulated (ES) and control (NS) pork carcasses. In samples taken at 3 min postmortem, type I fibers had the lowest ATPase activity staining and type 2X and 2B had the highest activity staining, with type 2A fibers intermediate. Postmortem time and carcass treatment did not influence the ATPase activity staining of type I muscle fibers. ATPase activity staining of 2A fibers was lower (p<0.001) in 24 h samples than in 3 min samples from ES carcasses. In 3 min and NS-24 h samples, RST type 2A fibers had lower (p<0.05) activities than type 2A fibers from the WST. In type 2X fibers, ATPase activity staining decreased (p<0.01) from 3 min to 24 h postmortem in ES carcasses. This decrease was more severe in WST 2X fibers compared to RST 2X fibers. ATPase activity staining in type 2B fibers did not decrease from 3 min to 24 h postmortem in NS carcasses. In ES carcasses, activity staining of 2B fibers decreased (p<0.0001) with time postmortem. The results of the experiment indicate that fibers expressing fast MyHC isoforms have a higher ATPase activity early postmortem than slow muscle fibers but are more prone to inactivation by a rapid pH decline. PMID- 22062536 TI - Influence of cattle breed and ageing time on textural meat quality. AB - An experiment was carried out using 7 month old male calves from four different breeds: 10 Spanish Holstein (dairy), 10 Old Brown Swiss (dual purpose), 10 Limousin (fast growth) and 10 Blonde d'Aquitaine (high muscularity). They were all fed concentrate and cereal straw ad libitum. Animals were slaughtered at usual commercial weights for the Spanish market depending on the growth and precocity of each breed (500 kg liveweight at slaughter for Holstein, 550 kg for Old Brown Swiss, 560 kg for Limousin and 620 kg for Blonde d'Aquitaine, with an age between 13 and 15 months). There were significant differences (P<0.001) among breeds in the quantity of total and insoluble collagen in the Longissimus thoracis and lumborum muscle, but collagen solubility was similar (41-44%), except for muscle from the Old Brown Swiss (33%; P<0.001). Overall, breeds specialized for beef production (Limousin and Blonde d'Aquitaine) had lower values for compression and WB in raw and heated meat, respectively, for ageing periods of less than a week. Ageing had a larger effect on myofibrillar tenderness than breed and tended to eliminate the breed effect on textural variables, as well as individual differences within each breed. PMID- 22062537 TI - Predicting the amount of carbon dioxide absorbed in meat. AB - Carbon dioxide is commonly used in modified atmosphere packaging of meat and the gas is highly soluble in meat. Both intrinsic (pH, water and fat content) and extrinsic (CO(2) partial pressure, headspace to meat volume ratio and storage temperature) factors affect the amount of CO(2) absorbed in meat. A multi factorial packaging experiment using minced pork was carried out in order to evaluate the effect of such factors under realistic conditions and to develop models for prediction of the amount of absorbed CO(2). For most practical applications CO(2) partial pressure and headspace to meat volume ratio are the key factors determining CO(2) absorption in meat. For volume ratios of more than 2 L gas/kg meat, knowledge of the partial pressure of CO(2) was sufficient to predict the amount of absorbed CO(2). PMID- 22062538 TI - Sensory and instrumental analysis of longitudinal and transverse textural variation in pork longissimus dorsi. AB - In the present study sensory and instrumental analysis of the textural properties of pork longissimus dorsi were performed and analysed using multivariate data analytical methodologies. The aims were to determine how textural properties of musculus longissimus dorsi varied transversely, longitudinally, between left and right muscles, and as a function of ageing. By training the panel in the descriptive texture profile method the panellists were able to clearly detect, discriminate and describe the textural variation in the samples, except for the transverse variation. Sensory evaluation revealed a non-significant trend (P>0.05) of decreasing tenderness from dorsal (nearest the spinal column) to medial sampling position. When analysed instrumentally, using a modified Warner Bratzler shear force apparatus, the transverse muscle variation was found to increase in force (N) required for deformation from dorsal to lateral sampling position. Overall, these two methods agreed in that the dorsal position was the more tender of the three positions investigated. Lengthwise muscle variation was highly defined when assessed using sensory analysis, whereas instrumental analysis was unable to detect this variation. The sensory analysis revealed that tenderness decreased and hardness increased as the sample position approached the caudal end of the muscle. Additionally, sensory analysis revealed a major turnover point in textural properties at the end of the ribcage area in that tenderness showed a marked decrease in this area and hardness and juiciness increased correspondingly in the same area. Both sensory and instrumental analysis showed that muscles from left and right side of the carcass differed significantly (P<0.05) in their textural properties. The right side muscle was clearly defined into stages more so than the left side muscle. In addition, the right loin was found to be harder per se than the left loin, which was postulated to be caused by a greater amount of work performed by right muscles compared to left muscles. Significant differences (P<0.05) in sensory textural attributes were observed overall with increased ageing. The variation within muscles, which contributed to the overall change in texture with ageing, was found to be due to changes in the longitudinal variation, in that the individual chop variation observed at the cranial end became less pronounced when the meat was aged. Differences observed between the cranial and caudal end remained, regardless of ageing for 4 or 7 days. No changes could be seen in the transverse texture during ageing. In general, sensory and instrumental analyses were found largely to be predictive indexes of each other. However, these two methods could not be said to be causally predictive in that they did not measure the same physical properties of the meat. For instance sensory determined tenderness is a result of the type and rate of deformation and the heterogeneity of the sample assessed, whereas instrumental measurement is a result of resistance to shearing. The present study showed significant variation between longitudinal locations and this variation is critical when designing sensory texture profiling experiments of meat from loins. Moreover, the textural differences between left and right loin muscles must be considered when texture prediction is the objective if an applicable conclusion is to be drawn. PMID- 22062539 TI - Testing for bias between the Kjeldahl and Dumas methods for the determination of nitrogen in meat mixtures, by using data from a designed interlaboratory experiment. AB - Bias between the Dumas and the Kjeldahl methods for the determination of protein nitrogen in food was studied by conducting an interlaboratory study involving 40 laboratories and 20 different test materials. Biases were found to be small and statistically significant only for the chicken test materials, where a bias of 0.020+/-0.004% m/m was detected. PMID- 22062540 TI - Factors regulating lamb longissimus tenderness are affected by age at slaughter. AB - The objective of this experiment was to determine age-related changes in collagen concentration, sarcomere length, calpain (MU- and m-) and calpastatin activities, postmortem proteolysis and Warner-Bratzler shear force (WBSF) in ovine longissimus thoracis et lumborum. Rambouillet lambs were slaughtered at 2, 4, 6, 8 and 10 months of age and samples of longissimus were collected at 0, 2 and 10 days postmortem. Collagen concentration and sarcomere lengths were determined from the cores used for WBSF measurements and reflected changes in the background toughness. Longissimus collagen concentration did not change (P>0.05) due to lamb age. Sarcomere lengths also showed age-related changes, increasing (P<0.05) from 1.35 MUm at 6 months to 1.48 and 1.55 MUm at 8 and 10 months, respectively. The extent of calpain mediated proteolysis determines the improvement in meat tenderness with postmortem storage. The most notable change in the calpain proteolytic system was the decline (P<0.05) in calpastatin activity from 4.18 to 1.91 U/g muscle between 2 and 10 months. The activity of MU-calpain showed a 16% increase (P<0.05) from 4 to 6 months, before it dropped again at 8 and 10 months. There was a gradual decline (P<0.05) in m-calpain activity with age, and by 10 months m-calpain activity had reduced to 80% of 2 months levels. The ratio of MU calpain to calpastatin activities increased (P<0.05) from 2 to 6 months (from 0.31 to 0.56) with no further changes (P>0.05) at 8 or 10 months. There were no age-related changes (P>0.05) in desmin degradation at day 2, however, examination of day 10 samples showed increased (P<0.05) degradation from 2 to 6 months. Thus, the changes observed in the ratio of MU-calpain to calpastatin activities are reflected in the extent of postmortem proteolysis. Meat tenderness was measured using WBSF at 2 and 10 days postmortem. Because little proteolysis had taken place at 2 days postmortem, the decline in day 2 WBSF from 6 to 8 months could be explained by changes in sarcomere length. However, at 10 days postmortem, where WBSF was shown to decrease from 2 to 8 months, the improvement in tenderness could be explained by the amount of postmortem proteolysis. The data presented in this paper show evidence that sarcomere length is the main determinant of background toughness in ovine longissimus, and that postmortem proteolysis, resulting from MU-calpain activity regulated by calpastatin, is the main determinant of ovine longissimus tenderization during aging. Thus, lamb longissimus tenderness after refrigerated storage is determined by postmortem proteolysis and its interaction with sarcomere length. PMID- 22062541 TI - Colour changes and consumer acceptability of bulk packaged pork retail cuts stored under O(2), CO(2) and N(2). AB - A centralised bulk packaging technique, utilising various gas mixtures, c. 100% CO(2)+oxygen scavenger, c. 80% O(2):20% CO(2) and c. 25% CO(2):50% N(2):25% O(2), was evaluated in terms of consumer acceptability and colour. The inclusion of an oxygen scavenger ensured that pork retail chops bulk packaged in a 100% CO(2) were as acceptable after 0, and 14 days bulk storage and subsequent retail display than chops stored in oxygen-enriched atmospheres. The study also indicated that a saturation level of 10 and higher indicated that the appearance of the pork chop was acceptable to the consumer panel. From the results of this study it is apparent that consumers find pork retail packs, bulk packaged in oxygen depleted atmospheres, as acceptable as pork chops stored in oxygen enriched atmospheres. PMID- 22062542 TI - Display life of sheep meats retail packaged under atmospheres of various volumes and compositions. AB - Longissmus dorsi loins were removed from Suffolk cross-breed lambs (4-9 months) and hoggets (15-20 months). The effect of package gas composition was investigated by packaging loins with gas mixtures containing 80:20:0, 60:20:20 and 60:40:0/O(2):CO(2):N(2) with a 2:1 headspace to meat volume ratio. The most effective gas mixture for prolonging shelf-life was used to study the effect of different headspace to meat volume ratios. Loins were packaged with a headspace to meat volume ratio of 2:1, 1.5:1 or 1:1. All modified atmosphere (MA) packs were held under refrigerated display conditions (4 degrees C, 616 lx) for 12 days. Loins were assessed for microbial, oxidative and colour stability and headspace composition every 3 days. The 80:20:0/O(2):CO(2):N(2) gas composition and the 2:1 headspace to meat volume ratio was the most effective packaging combination at maintaining and prolonging the attractive red colour of MA packaged lamb and hogget meat. 80:20:0/O(2):CO(2):N(2) resulted in significantly (p<0.01) higher Hunter a values in lamb. The 2:1 ratio gave higher visual assessment values in lamb and higher Hunter 'a' values for hogget meat throughout the trial. The 2:1 ratio was the most effective at decreasing Pseudomonas and increasing the numbers of lactic acid bacteria in the total microbial load in both lamb and hogget meat. Lipid oxidation in lamb and hogget meat occurred at a slower comparative rate than discolouration or microbial growth and was not the major determinant of shelf-life. The 2:1 headspace to meat volume ratio was most effective at maintaining the initial gas mix in both lamb and hogget MA packs. PMID- 22062543 TI - Fatty acid composition and tocopherol concentrations in muscle of entire male, castrated male and female pigs, reared in an indoor or outdoor housing system. AB - The objective of this study was to investigate the effect of outdoor rearing on the fatty acid (FA) composition and contents of tocopherols of M. longissimus dorsi polar (PL) and neutral lipids (NL) in entire males, castrated males and female pigs. Fat content did not differ between genders or rearing conditions. In PL of the indoor pig muscle the level of n-6 highly unsaturated fatty acids (HUFA) was higher in females and entire males compared with castrated males. The outdoor environment resulted in a slightly higher level of n-3 polyunsaturated FA (PUFA) in muscle PL and NL of entire males compared with females and castrated males. We also found an increased level of 18:2 n-6 in the muscle PL of outdoor reared females compared with the indoor females. The higher levels of PUFA in the entire male muscle, in both PL and NL, were not accompanied by a higher level of vitamin E. PMID- 22062544 TI - Visualization of drip channels in meat using NMR microimaging. AB - The progressive changes in the water distribution within rabbit muscles were studied by nuclear magnetic resonance microscopy during the first 24 h postmortem. T(2) images revealed development of interspersed lines with higher signal intensities in the muscle, reflecting formation of channels containing mobile water. The appearance of the interspersed lines progressed throughout the measuring period and became increasingly evident. After about 3 h postmortem the signal intensity also increased in areas near the surface of the samples, which reflects migration of the mobile water to the sample surface. Proton density images showed the presence of a chemical shift artifact in the interspersed lines, implying that the intrinsic development of water channels progressed in close proximity to the connective tissue. PMID- 22062545 TI - Growth of Listeria monocytogenes on vacuum-packaged horsemeat for human consumption. AB - In order to investigate the likelihood of Listeria monocytogenes (serotype 4b, ATCC 19115) growth on vacuum-packaged horsemeat at refrigeration temperature, fourteen horsemeat surface/volume homogeneous 150 g weight pieces were superficially inoculated with serotype 4b L. monocytogenes and vacuum packaged. The samples were stored at 4+/-1 degrees C. Two pieces (one for pH determination and one for L. monocytogenes counts) were examined at days 0, 7, 14, 21, 28, 35 and 42. Surface pH did not show significant variations during the experiment. The average L. monocytogenes initial contamination level was 1.77log(10) CFU/g. A lag phase of 7 days was recorded. The exponential growth rate between day 7 to day 35 was 0.125log(10) CFU/day, corresponding to 3.51log(10) CFU/g in 28 days. At the end of the experiment the mean L. monocytogenes log(10) CFU/g was 5.78. PMID- 22062546 TI - Comparison of human papillomavirus testing and cytology for cervical cancer screening in a primary health care setting in the Democratic Republic of the Congo. AB - OBJECTIVES: We compared the screening performance of conventional Pap cytology and two human papillomavirus (HPV) DNA assays, the original Hybrid Capture 2 (HC2) and an expanded version that tests for 4 additional HPV types (HC2+4; Qiagen Corporation), in the detection of cervical neoplasia among unscreened women in a primary care setting in a suburb of Kinshasa, Democratic Republic of the Congo. METHODS: All women 30 years or older residing in the area were invited to participate, and 1528 were evaluated by Pap cytology and the two HPV assays, conducted at a European and US reference laboratory, respectively, followed by colposcopy. Cervical biopsies were obtained from all women with abnormal colposcopy and from 290 randomly chosen women with normal colposcopy (to correct for verification bias). RESULTS: Using a relative light unit of 1 as the cutoff for positivity, 169 and 168 (11%) women tested positive using HC2 and HC2+4, respectively. HC2 and HC2+4 were in agreement in 98.6% of cases (Kappa=0.94; 95% confidence interval: 0.91-0.96). Both assays were sensitive (~83%) and specific (~91%) for the detection of cervical intraepithelial neoplasia-2 or worse disease. Irrespective of the cutoff point used to define positivity, Pap cytology was both less sensitive and more specific than HC2 or HC2+4. For instance, cytology was 63% sensitive and 97% specific when a cutoff point of low-grade squamous intraepithelial lesions or worse was used. CONCLUSIONS: Among unscreened women, HC2 and HC2+4 had similar screening accuracy for cervical neoplasia, and both were more sensitive but less specific than Pap cytology. PMID- 22062547 TI - Discounting of sequences of delayed rewards of different amounts. AB - The main purpose of this study was to determine whether the magnitude effect is present in cases where delayed sequences of rewards are discounted. The magnitude effect refers to the inverse relationship between the amount of a reward and the steepness of temporal discounting. This study was conducted with a computer program to estimate the indifference points, which served as indicators of the present subjective value of delayed sequences of small and large rewards. In the indifference point the subjective value of a single, immediate reward was equal to the subjective value of the delayed sequence (or to the value of a single delayed reward). As a control condition, we added an experimental task involving choices between single immediate and single delayed rewards. The experiment showed that the sequences of large rewards are discounted less steeply than are the sequences of small rewards. This finding suggests that the magnitude effect is present within the delayed sequences of rewards. In addition, when outcomes are relatively large, the results suggest that a single reward is discounted less steeply than the sequence of a total nominal value equal to this single reward. However, for relatively small rewards, the difference is not statistically significant. The less steep discounting of sequences of large rewards may explain the reward-bundling effect, which refers to less steep discounting of longer sequences than of shorter ones: longer sequences usually have greater overall nominal value. The present study was conducted on hypothetical rewards, and the results should be validated using real rewards. PMID- 22062548 TI - The hsa-miR-5787 represses cellular growth by targeting eukaryotic translation initiation factor 5 (eIF5) in fibroblasts. AB - MicroRNAs (miRNAs) are small non-coding RNAs that regulate diverse biological processes. We cloned novel small RNA from human mesenchymal stem cells (hMSCs) and termed microRNA-5787 (hsa-miR-5787) that met the criteria for a miRNA. The level of miR-5787 was elevated in senescent fibroblasts. Based on the target prediction algorithm and results that were obtained, we find that eukaryotic translation initiation factor 5 (eIF5) is a target of miR-5787. Similar to the over-expression of miR-5787, we showed that repression of eIF5 in fibroblasts negatively affected cell growth. Therefore, we propose that the miR-5787 represses cell growth, in part, by targeting eIF5. PMID- 22062549 TI - Impact of host responses on control of hepatitis C virus infection in Chinese blood donors. AB - A study was undertaken to explore the molecular mechanisms underlying control of HCV infection in blood donors in China. Factors including clinical information, anti-HCV reactivity (S/CO), IFN-alpha and IFN-gamma, viral loads and genotypes were correlated with 160 index plasma samples at three statuses of 45 recovered, 76 chronic or 39 false positive anti-HCV reactive blood donors. The spontaneous recovery rate was 37.2%. Viral loads of 76 HCV plasmas ranged between 59.8 IU/ml and 2.43 * 10(6)IU/ml (median 3.67 * 10(4)IU/ml). Genotypes 1, 2, 3 and 6 of 63 HCV strains were identified phylogenetically. Recovered donors were significantly younger (p=0.002) and had lower level IFN-gamma (p=0.001) than chronically HCV infected donors. Circulating levels of IFN-alpha and IFN-gamma were higher in those with low viral load and were low in middle or high viral load samples. The ratio of IFN-alpha to IFN-gamma (IFN-alpha/gamma) was significantly positively correlated with viral load (p=0.037), and viral load was inversely correlated with IFN-gamma in chronic HCV infection regardless of genotype. The study revealed clearly different relationships between IFN-alpha and IFN-gamma in relation to viral load in HCV. A novel measure of IFN-alpha/gamma ratio could be a new approach to evaluate long term outcome of HCV infection. PMID- 22062550 TI - The effect of air temperature, velocity and visual lean (VL) composition on the tempering times of frozen boneless beef blocks. AB - Beef blocks of two compositions, 100% and 50% visual lean (VL), in standard commercial packaging with nominal dimensions of 510*390*150mm were tempered from 18 degrees C to -3 degrees C using air at temperatures from 3 degrees C to -3 degrees C and velocities of 0.5 and 5ms(-1). These conditions were then modelled using a finite difference mathematical model and the accuracy of the model assessed by comparison with the experimental results. An extended range of conditions (including an intermediate air velocity of 2ms(-1) and an intermediate composition of 75% VL) was then modelled to produce data that can be used to design tempering processes. The results show that single stage air tempering of even single blocks within their cartons needs to be a long process. In air at 3 degrees C and 5ms(-1), blocks of 50% VL rose to deep temperatures of -10 degrees C and -3 degrees C after 4.0 and 22.5h, respectively, while with 100% VL 4.6 and 27.3h were required. Under these conditions, the surface layers of the meat would have spent many hours in a thawed condition that would be detrimental to both drip and optimal processing. Using lower temperatures avoids thawing and at the same time produces an optimum temperature difference for subsequent processing. However, tempering times are substantially extended. For example, times to the above temperatures using air at -1 degrees C and 5ms(-1) were 4.8 and 37.5h for 50% VL and 5.1 and 44.5h for 100% VL. PMID- 22062551 TI - Influence of season, distance and mixed loads on the physical and carcass integrity of pigs transported to slaughter. AB - To determine the influences of season, distance and multiple-farm loads on pigs transported to slaughter under Spanish commercial conditions, 496 journeys, involving 90,366 pigs, were analysed. Mortality, liveweight loss, transport yield, killing out percentage, carcass yield after overnight chilling and percentage of condemned and trimmed carcasses were recorded. Season significantly affected killing out percentage and trimmed carcasses, with the lowest values found in autumn and summer, respectively. Distance significantly affected liveweight loss and transport yield. Loads composed of pigs from a number of farms had more deaths and carcass problems. It can be concluded that, under Spanish climatic conditions, if journey planning and handling at loading are adequately performed, season and distance do not impair the welfare of slaughter pigs. On the other hand, loading at a number of farms, alone, or interacting with distance, can compromise pig welfare. PMID- 22062552 TI - Characterization of Staphylococcus xylosus and Staphylococcus carnosus isolated from Slovak meat products. AB - The aims of this study were to isolate, identify and characterize the population of coagulase-negative staphylococci in different types of Slovak traditional sausages and to determine the metabolic properties of selected Staphylococcus xylosus and S. carnosus strains for the selection of potential starter cultures to use in the processing of sausages. The strains were tested for lactic acid production, survival in the presence of bile and sensitivity to antibiotics. Bacteriocin production, adhesion ability as well as biogenic amine (BA) production by isolates were also analysed. Most of the isolates were identified as S. xylosus and S. carnosus. Lactic acid values ranged from 0.40 to 1.03mmol/l and strains survived in the presence of 1% bile. Most of the strains studied were sensitive to all antibiotics. Two strains, S. xylosus SO3/1M/1/2 and S. carnosus SO2/F/2/5 inhibited Listeria innocua and Pseudomonas sp. S. xylosus strains did not produce any BA, while S. carnosus SO2/F/2/5 did. S. xylosus SO3/1M/1/2 and S. carnosus SO2/F/2/5 appeared as the most adhesive strains. S. xylosus SO3/1M/1/2 with antimicrobial activity against Enterococcus avium EA5, L. innocua LMG13568 and Pseudomonas sp. SO1/1M/1/4, adhesion ability and free BA production could be used as starter culture in sausage manufacture. PMID- 22062553 TI - The colour of the adductor muscle as a predictor of pork quality in the loin. AB - The relation between measurements of colour made in the m. adductor (AD) at 45min or 20 h post mortem and the quality, assessed subjectively in terms of colour and waterholding capacity, of the m. longissimus (LD) in the loin was examined. The study used data from 100 pig carcasses exhibiting a wide range of meat quality from extreme PSE (pale, soft and exudative) to extreme DFD (dark, firm and dry). The subjective assessments were confirmed by objective measures of paleness (reflectance) and waterholding capacity (drip loss in storage) in the LD. Lightness (L(*)) measured at 20h post mortem in the AD was the best potential predictor of loin muscle quality, explaining 59% of the variation in subjective and objective quality measures. Comparable measurements at 45min post mortem explained between 21% and 44% of the variation. The equation that described the relation between AD Lightness (L(*)) and subjectively assessed LD quality was derived. This could be used to transpose the AD L(*) values from a population of slaughtered pigs into nominal subjective scores for the LD, allowing the frequency of the five subjective quality groups (extremely DFD, slightly DFD, normal, slightly PSE, and extremely PSE) in the population of carcasses to be defined. PMID- 22062554 TI - Chemical and microbiological characterization of alheira: A typical Portuguese fermented sausage with particular reference to factors relating to food safety. AB - Alheiras are traditional smoked naturally fermented meat sausages produced in the north of Portugal. They have not previously been characterized as to their chemical and microbiological status. pH and salt levels are insufficient to assure microbiological safety, there is ample opportunity for post-cooking contamination; the products require chill storage and cooking before consumption. Heavy metals and biogenic amines were, in general, within accepted limits for meat products. Lactic acid bacteria comprised the major microflora (ca. 7 8logcfu/g) with substantial counts of micrococci and enterococci (up to 7logcfu/g). Escherichia coli, Staphylococcus aureus and Listeria spp. were detected in several samples. PMID- 22062555 TI - Quantification and kinetics of the residual brine generation during ham and shoulder pile salting. AB - Salting is one of the most important stages of the traditional process of cured ham manufacturing. During pile salting a saturated brine is formed and drips through the orifices located at the bottom of the salting containers. The objective of the present work was to quantify the released brine in the ham manufacturing industry in Spain and to relate the brine generation with the salt gained by hams in the process. The total released brine during ham and shoulder salting in Spain was determined theoretically and from the experimental values obtained from the industry (around 38,000 metric tons in 2002). In addition to that, an easy method for the estimation of the NaCl gained by hams and shoulders was developed by using the measurements of the released brine (the estimated NaCl gained differed 3.5% from the experimental data). PMID- 22062556 TI - Dry-cured ham quality and acceptability as affected by the preservation system used for retail sale. AB - Dry-cured ham cuts and slices were stored at 4+/-2 degrees C for 8 months under vacuum and modified atmosphere (20% CO(2)+80% N(2)), respectively. Instrumental colour and texture, pH, non-protein nitrogen, total volatile basic nitrogen, acidity, lipid oxidation, sensory profile and consumer acceptability and purchase satisfaction were measured throughout storage. The overall quality of vacuum packaged dry-cured ham cuts showed limited changes. Significant changes of sensory attributes involved only loss of flavour. The overall acceptability assessed by both trained and consumer panels did not decrease significantly throughout storage and the willingness to purchase remained above 50%. Conversely, modified-atmosphere-packaged ham slices had intense and extensive changes affecting sensory quality, particularly in visual appearance, flavour loss, off-flavour formation, saltiness and rancidity. Some of these changes were related to oxidation caused by low pH due to the presence of carbon dioxide in the protective atmosphere. Acceptability was significantly lower from the 4th month of storage and willingness to purchase fell below 50% at the same time. PMID- 22062557 TI - Augmented postmortem glycolysis does not occur early postmortem in AMPKgamma3 mutated porcine muscle of halothane positive pigs. AB - The objective of this study was to determine the effects of the halothane (HAL) and Rendement Napole (RN) genes on the rate-limiting reactions of glycolysis and their relationship to pork quality development. Samples were collected from the longissimus muscle at 0, 30, 60, and 120min and 24h postmortem from homozygous HAL and RN pigs (NN/rn(+)rn(+), NN/RN(-)RN(-), nn/rn(+)rn(+), nn/RN(-)RN(-)). Muscle pH was recorded at 0, 15, and 45min, and 24h postmortem. HAL mutants, compared with HAL normal, had lower (P<0.05) ATP concentrations at 0 and 30min, lower (P<0.05) pH at 45min, and hastened glycogen degradation and lactate accumulation in the first 120min postmortem (HAL*time, P<0.0001). RN mutants had greater (P<0.0001) glycolytic potentials than RN normal, and lower (P<0.05) 24h pH compared with the normal genotype, but not the HAL mutant genotype. The HAL mutation negatively affected (P<0.05) L*, b* and color scores whereas both HAL and RN mutations independently decreased (P<0.05) firmness, marbling and water holding capacity. RN mutant genotypes had higher (P<0.0001) phosphocreatine concentrations than other genotypes at 0min. Compared with HAL normal, HAL mutants had elevated (P<0.05) muscle glucose concentrations at 30, 60, and 120min, and 24h. RN mutants had higher (P<0.05) glucose levels than RN normal after 60min. Glucose-6-phosphate (G6P) concentrations decreased (P<0.05) during the first hour postmortem except in HAL/RN mutants, which had higher (P<0.01) G6P concentrations than all other genotypes at 30min. From 60min to 24h postmortem, G6P increased (P<0.05) in HAL normal genotypes. Altogether, these data show that elevated muscle glycogen content does not further aggravate rapid early postmortem metabolism. PMID- 22062558 TI - Effect of dietary ractopamine on tenderness and postmortem protein degradation of pork muscle. AB - Twenty-four finishing pigs with a mean starting weight of 82kg were assigned to two dietary regimens: (1) a corn-soybean meal basal diet (control; n=12), and (2) the basal diet supplemented with 20ppm ractopamine HCl (RAC; n=12). After 28-30 days on the feeding trial, pigs were slaughtered, and the growth and carcass characteristics were measured. Furthermore, the 3rd-13th rib section of longissimus muscle was excised at 48h postmortem, sliced into 19-mm thick chops, vacuum packaged, stored at 2 degrees C, and subjected to Warner-Bratzler shear force (WBSF) and electrophoretic tests after 2, 4, 7, 10, 14, and 21 days (postmortem). RAC feeding increased (P<0.01) pig carcass weight and percent lean, but it also increased the day-2 muscle WBSF by 20% (P<0.01). The shear force difference between control and RAC pig muscles gradually decreased and vanished by day 10 (P>0.05) when both muscle groups became more tender. The muscle from RAC-fed pigs exhibited a slower protein degradation rate than muscle from the control animals, notably for proteins in the 15-45kDa range. The results suggested that the tenderness difference between ractopamine-treated and control pig muscles was related to the proteolysis rate, and could be diminished with adequate postmortem ageing. PMID- 22062559 TI - The effect of modified atmosphere packaging with carbon monoxide on the storage quality of master-packaged fresh pork. AB - Modified atmosphere packaging with carbon dioxide is effective for prolonging shelf-life of fresh meat. Addition of carbon monoxide to the system provides the advantage of enhancing meat colour. The study objective was to determine the effect of CO(2)-MAP+0.4% CO, vs. 100% CO(2)-MAP, on the bacteriology and colour of retail-ready fresh pork stored for 8 weeks in a master-package system. Total plate counts were not affected and listeria was present on meat from both treatments. Colour was enhanced with the inclusion of CO, while no effect on lipid oxidation was observed. Use of CO in MAP provides sufficient storage life and product colour quality to permit shipment of fresh pork to distant markets. However, given the stable fresh colour of CO-treated meat and the lack of inhibition of pathogen growth by CO, there is concern that CO-MAP under certain conditions may pose a food safety risk. PMID- 22062560 TI - Optimization of emulsion characteristics of beef, chicken and turkey meat mixtures in model system using mixture design. AB - Emulsion pH (pHe), emulsion capacity (EC), emulsion stability (ES), emulsion density (ED) and apparent yield stress of emulsion (raw emulsion, AYSe) and emulsion gel (cooked emulsion, AYSg) of beef, chicken and turkey meats and their mixtures were studied using a model system. Turkey meat homogenate was found to have higher protein concentration than chicken or beef homogenates. The highest pHe, EC and ES values and the lowest ED and AYSe values were found in chicken meat. However, the highest AYSg value was found in chicken-turkey meat mixture. Generally, the increasing amount of chicken meat in mixtures increased EC and ES, and decreased ED and AYSe values. Also, chicken-turkey meat mixtures had lower ES values than the mixtures containing only chicken or only turkey meat. With beef, the addition of chicken and turkey meats improved emulsion characteristics significantly. Optimum levels of beef, chicken and turkey meats were found to be 0-23%, 9-30% and 53-91% respectively. PMID- 22062561 TI - Effects of age on composition and quality of muscle Longissimus thoracis of the Omani Arabian camel (Camelus dromedaries). AB - The aim of this study was to determine the effects of age on chemical composition and quality characteristics of the Arabian one-humped camel's meat. Samples of longissimus thoracis (between the 10th and the 13th rib of the left side) were randomly collected from 21 Omani intact male camels of three different age groups: group 1 (1-3 years), group 2 (3-5 years) and group 3 (6-8 years). Samples were chilled (1-3 degrees C) for 48h. Moisture, crude protein, fat and ash were determined on freeze dried ground muscle. Mineral contents were determined using an Inductively coupled plasma emission spectrometer (ICP). Meat quality including ultimate muscle pH, Warner-Bratzler shear force, sarcomere length, myofibrillar fragmentation index, expressed juice, cooking loss percent, and colour L(*), a(*), b(*) were measured using standard methods. The moisture, protein, fat and ash ranged from 64.4% to 76.7%; 18.6% to 25.0%, 1.1% to 10.5% and 1.0% to 1.4% on dry matter basis, respectively. The Ca, Mg, Na, K, P, Cad, Cr, Ni, Pb, Co, Mo, Be and V ranged from, 9.2 to 46.6, 24.7 to 57.3, 104.7 to 257.0, 471.4 to 1053.0, 249.9 to 584.0, 0.005 to 0.024, 0.020 to 0.410, 0.016 to 0.187, 0.010 to 0.299, 0.010 to 0.018, 0.050 to 0.470, 0.005 to 0.030 and 0.013 to 0.141mg/100g on dry matter basis, respectively. The percentage of protein decreased and that of fat increased with increasing camel age. The ultimate pH, shear force, sarcomere length, fragmentation index, expressed juice, cooking loss, lightness (L(*)), redness (a(*)) and yellowness (b(*)) ranged from 5.46 to 6.64, 4.25 to 17.82, 0.96 to 2.50, 55.91 to 94.81,19.50 to 33.63, 13.18 to 29.88, 27.86 to 43.21, 10.46 to 22.81, and 4.63 to 10.11, respectively. Muscles of younger camels (group 1) had significantly (P<0.05) lower shear force value, ultimate pH and higher sarcomere length, fragmentation index, expressed juice, cooking loss, and lightness color (L(*)) by 48%, 3.4%, 43%, 25%, 28%, 14%, and 16% than those collected from older camels (group 3), respectively. Values of middle age camels (group 2) camels were in-between. This study confirmed that camel meat is healthy and nutritious as it contains low fat as well as being a good source of minerals. Age is an important factor in determining meat quality and composition. PMID- 22062562 TI - Effects of transportation at high ambient temperatures on physiological responses, carcass and meat quality characteristics of three breeds of Omani goats. AB - The experiment was designed to determine the effects of short road transportation in an open truck during the hot season on live weight shrink, physiological responses, carcass, and meat quality characteristics in three breeds of Omani goats. Forty-two male goats (12months of age) representing equally three breeds of Omani goats (Batina, Dhofari, and Jabal Akhdar) were divided into two groups: 2h transportation stress (TS) or not transported (NT). The NT group remained unstressed in holding pens with feed and water provided ad libitum prior to slaughter, while the TS group was transported on the day of slaughter 100km in an open truck. The average temperature during transportation was 37 degrees C. All animals were blood-sampled before loading and prior to slaughter via jugular venipuncture. Animals were weighed just before loading onto a truck and after transport to assess shrinkage. Muscle shear force, sarcomere length, pH, expressed juice, color, and cooking loss were measured on samples from Mm longissimus dorsi (LD), biceps femoris (BF), and semitendinosus (ST) muscles collected at 24h postmortem at 1-3 degrees C. Live weight shrinkage losses were between 1.07 and 1.28kg. The TS goats had higher plasma cortisol (P<0.01), adrenaline, nor-adrenaline, and dopamine concentrations (P<0.05) than NS goats. Blood serum from Batina goats had significantly (P<0.05) higher cortisol, adrenaline and dopamine and nor-adrenaline concentrations than those from Jabal Akdhar goats. Transportation stress had a significant (P<0.05) effect on meat quality characteristics of the LD, BF, and ST muscles. Meat from TS goats had significantly higher ultimate pH, expressed juice, cooking loss percentage, shear force, but significantly lower sarcomere length, L(*), a(*), and b(*) values. LD muscles of Batina goats had significantly higher ultimate pH values and lower L(*) values than Dhofari and Jabal Akdhar goats. These results indicated that subjecting goats to the 2-hour road transportation with high ambient temperatures can generate major physiological and muscle metabolism responses. PMID- 22062563 TI - Mineral analysis in rabbit meat from Galicia (NW Spain). AB - A total of 54 rabbits 50, 70 and 90 days old, were taken from farms in Galicia (NW Spain); 18 rabbits of each age were sampled. The minerals in the muscle meat from the back legs of the rabbits were analysed, and the following average concentrations were found: ash 1.21/100g, potassium 388mg/100g; phosphorus 237mg/100g; sodium 60mg/100g; magnesium 27mg/100g; calcium 8.7mg/100g; zinc 10.9mg/kg; iron 5.56mg/kg; copper 0.78mg/kg; and manganese 0.33mg/kg. The high potassium and low sodium concentration may make rabbit meat particularly recommended for hypertension diets. Rabbit meat is rich in phosphorus, and 100g provides approximately 30% of the recommended daily intake. However, rabbit meat provides less zinc and iron than meats of other species. The Galician rabbit meat analysed in this study, shows higher copper and manganese, and lower calcium contents than those found in the literature for rabbit meat of other origins. PMID- 22062564 TI - Content of biologically active polyamines in livers of cattle, pigs and chickens after animal slaughter. AB - Dietary polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM) participate in an array of important human physiological roles, including tumour growth. Physicians and dieticians thus need reliable information on polyamine contents in foods. However, data for livers are lacking. We determined therefore the content of these polyamines 24h after slaughter in livers of young bulls, cows, pigs and chicken in 58, 19, 36 and 38 samples, respectively. Polyamines were determined as N-benzamides by micellar electrokinetic capillary chromatography. Mean PUT contents about 25mgkg(-1) were found in cattle livers, while very low or negligible contents were determined in livers of the other animals. Extremely high mean SPD contents of 122 and 161mgkg(-1) were found in livers of bulls and cows, respectively and mean levels of 32 and 57mgkg(-1) in livers of pigs and chicken. An opposite relation was observed for SPM. Its mean contents were 43, 35, 115 and 120mgkg(-1) for bulls, cows, pigs and chicken livers, respectively. Thus, livers of the tested animal species belong among foods with the highest polyamine contents. However, the contents ranged very widely, that makes application of the results for the control of human nutrition rather difficult. Polyamine contents in bovine blood were found to be below the detection limits of 2.1, 1.0 and 1.4mgkg(-1) for PUT, SPD and SPM, respectively. Thus, the blood content did not contribute to the substantial polyamine contents in bovine liver found in this study. PMID- 22062565 TI - Comparison of carcass and meat characteristics of three rabbit lines selected for litter size or growth rate. AB - Rabbits from three synthetic lines were compared. Line V and A were selected for litter size at weaning and line R was selected for growth rate between weaning and slaughter time. Forty animals of each line were slaughtered at 9week of age. Comparisons between lines were made using Bayesian statistical techniques. Line R had a higher meat/bone ratio, higher loin percentage and higher ultimate pH of M. Longissimus lumborum (LL) than A and V, but lower dressing out and lower hind part percentages. Some differences between lines in carcass and meat colour were found. No differences were found for percentage of released water of LL and for the activity of energy metabolic enzymes. At present, rabbit carcasses are not costed according to their retail cuts or meat/bone ratio, but dressing out percentage is taken into account, thus breeding companies should be concerned about lower carcass yield of lines selected by growth rate. PMID- 22062566 TI - Quality traits in muscle biceps femoris and back-fat from purebred Iberian and reciprocal Iberian*Duroc crossbred pigs. AB - The present study evaluated the physico-chemical characteristics of muscle biceps femoris and back-fat from purebred Iberian (PBI) pigs and reciprocal crossbred Iberian*Duroc pigs (IB*D pigs: Iberian dams*Duroc sires; D*IB pigs: Duroc dams*Iberian sires). Muscles from PBI pigs contained significantly higher amounts of IMF, heme pigments and iron than those from crossbred pigs. In addition, muscles from PBI pigs were darker (lower L(*)-values) and redder (higher a(*) values) and exhibited a more intense colour (higher chroma value) which was closer to the true red axis (lower hue value) than muscles from crossbred pigs. Back-fat from PBI pigs had significantly higher percentages of monounsaturated fatty acids (MUFA) and significantly smaller percentages of polyunsaturated fatty acids (PUFA) than those from crossbred pigs. Regarding the fatty acid profiles of the muscle lipid fractions, the genetic background particularly affected the composition of the polar lipid (PL) fraction. PL in muscles from PBI pigs contained significantly higher proportions of oleic acid and total MUFA and significantly lower amounts of arachidonic acid, certain long-chain PUFA (omega-6 and omega-3 fatty acids) and total amount of PUFA than PL in muscles from crossbred pigs. The results obtained indicate that tissues from PBI pigs would be more suitable for the production of dry-cured meats than those from cross-bred pigs. The position of the dam or the sire in reciprocal Iberian*Duroc crosses had no clear effects on meat quality. PMID- 22062567 TI - The influence of nitrite and nitrate on microbial, chemical and sensory parameters of slow dry fermented sausage. AB - Nitrate and/or nitrite are used in the manufacture of dry-fermented sausages. However, research has mainly been focusing on nitrite and its effect on flavour development whereas little attention has been paid to nitrate. The aim of the present work was to study the effect of nitrate and nitrite as curing salts on the quality of a slow fermentation process. Two different batches containing nitrate or nitrite were manufactured. Microbial and chemical parameters were monitored during ripening and after vacuum packed storage, as well as their fatty acid composition and their profile of volatile compounds. The oxidation, measured as TBARS (Thiobarbituric acid reactive substances), was greater in the samples with added nitrite than in the samples with added nitrate. FFA (free fatty acids) release was higher in the samples containing nitrite throughout the process. Volatile compounds arising from amino acid degradation and carbohydrate fermentation were generated at higher levels in the samples with added nitrate, probably due to the higher population of microorganisms in these samples and the effect of nitrate on their metabolism. PMID- 22062568 TI - Dry aging of beef in a bag highly permeable to water vapour. AB - The objective of this experiment was to compare traditional dry aging of beef with a novel technique of dry aging in a highly moisture-permeable bag. Four equal-sized sections from paired beef strip loins were dry aged traditionally, unpackaged, or packaged in the experimental bag for 14 or 21d at 3 degrees C. No differences (P>0.05) were noted for pH, moisture, fat, total plate counts, cook loss, shear force, or any measured sensory attribute between the two aging treatments after either aging period. After 21d, however, dry aging in the bag (versus traditional dry aging) decreased (P<0.05) weight loss during aging, trim loss after aging, and yeast counts on lean tissue and increased lactic acid bacteria counts (P<0.05) on adipose and lean tissue. Dry aging in a highly moisture-permeable bag is feasible, will positively impact yields and reduce microbial spoilage, and will have no negative impact on product quality. PMID- 22062569 TI - Effects of total iron, myoglobin, hemoglobin, and lipid oxidation of uncooked muscles on livery flavor development and volatiles of cooked beef steaks. AB - Infraspinatus (IN), gluteus medius (GM), and psoas major (PM) steaks were obtained from A- and B-maturity carcasses with either high (?6.0) or normal (?5.7) pH, and either Slight or Small marbling. Steaks were vacuum aged either 7, 14, 21, or 35d postmortem, and were broiled and served to a highly trained, flavor-profile sensory panel. Steaks with livery flavor were analyzed by gas chromatography/mass spectrometry for flavor compounds. Steaks aged 7 or 35d postmortem were analyzed for myoglobin (Mb) and hemoglobin (Hb) concentrations and for total iron (Fe) (35 d steaks only). The IN had greater Fe (P<0.05) than did the GM or PM. Livery flavor increased (P<0.05) and beef flavor identification decreased (P<0.05) in the GM as Fe increased. The PM had the lowest (P<0.05) Mb/Fe ratios and highest (P<0.05) Hb/Fe ratios. Several statistically significant, but relatively low correlations between 16-, 17-, and 18-carbon chain fatty acids and livery flavor resulted. Thirteen volatile compounds had higher concentrations in steaks with livery flavor than in those without livery flavor. Livery flavor development is a complex trait that can be affected by concentrations of total Fe, Mb, and fatty acids, but the relationships are relatively low. PMID- 22062570 TI - Comparison of texture and biochemical characteristics of three rabbit lines selected for litter size or growth rate. AB - Meat texture and some biochemical characteristics that could influence meat tenderness were studied in rabbit loins. Rabbits from three synthetic lines were compared, lines V and A selected for litter size at weaning and line R selected for growth rate between weaning and slaughter time. The activities of cathepsins, collagen content and textural properties measured by Warner-Bratzler (WB) shear device and by the texture profile analyses (TPA) test were measured. Line R was more tender than line V and line A had an intermediate tenderness, Rabbit meat from line R had higher activity of cathepsins B and B+L, lower total collagen content and lower cohesiveness, springiness and chewiness, shear force and total work (area under the curve obtained with WB device) than line V. Line A had an intermediate texture between lines R and V. Our results show evidence of genetic variation between lines in rabbit meat tenderness. PMID- 22062571 TI - Body composition of lambs receiving 30 or 60 days of exercise training and (or) fenoterol treatment. AB - The interaction between exercise and the beta-adrenergic agonist, fenoterol, on body composition and muscle protein turnover was studied in this investigation. Forty young Hampshire*Rambouillet lambs were assigned to control (CON), exercised (EX), fenoterol-treated (5 ppm) (FEN), or fenoterol-treated and exercised (FENEX) groups. Lambs assigned to the exercise treatments were trained to run on a 10 degrees inclined treadmill. The lambs were slaughtered after 30 or 60 days of treatment. Average daily gain tended (p=0.09) to be greater, and feed:gain was significantly lower (p=0.03) in the EX group than in the FENEX group by 30 days of treatment. By 60 days of treatment, kidney and pelvic fat and bodywall thickness were least in the EX group. Leg weights increased significantly with time only in the FEN and FENEX groups, whereas shoulder weights increased with time in all but the EX group. The latter effect was due to a cessation of adipose tissue growth in the EX lambs. There were significant time*treatment effects for the M. biceps femoris, M. gluteus medius, M. quadriceps femoris, M. semimembranosus, M. semitendinosus, M. infraspinatus, and M. pectoralis profundus. In every case, the time*treatment interaction was caused by nonsignificant growth of muscles in the CON group between 30 and 60 days. For the M. biceps femoris, M. quadriceps femoris, and M. gluteus medius, muscle mass increased with time only in the FENEX lambs. There was no increase in leg subcutaneous or intermuscular adipose tissue mass between 30 and 60 days in the EX lambs, although 50-70% increases in adipose tissue mass were observed over time in the other groups. Calpain and calpastatin activities in M. biceps femoris were not affected by treadmill exercise, fenoterol administration, or time*treatment (p>0.72 for all effects). Myosin light chain-1 gene expression in the FENEX lambs was depressed by 60 d, suggesting that the rate of M. biceps femoris growth in this treatment group was slowing by this time. PMID- 22062572 TI - Characterisation of low-fat high-dietary fibre frankfurters. AB - Two different peach dietary fibre (DF) suspensions (17 and 29%) were used to obtain low-fat high-DF frankfurters (20-5% fat) which were compared to an all meat control (25% fat). The viscosity of the meat batters increased with DF content. The protein (11.5+/-0.6%) and collagen (1.4+/-0.1%) contents of frankfurters were not affected by DF addition, and the higher the DF content, the lower the pH (6.4 to 5.8) due to the fibre solution acidity. The DF was effective in retaining added water in low-fat frankfurters since their cooking losses were similar to those of the controls (5.5+/-0.1%). Low-fat frankfurters were darker and browner than the controls and only high fibre addition significantly decreased the textural parameters. Sensory evaluation indicated that low fat-high DF frankfurters (20, 15 and 10% fat) were as acceptable as the all-meat frankfurters. PMID- 22062573 TI - Effect of natural colourants and nitrites on colour attributes of frankfurters. AB - The colour attributes in a control and six more treatments of frankfurters (18% fat) produced with natural colourants and two levels of NaNO(2) (0 and 150 mg/kg) were studied. The following natural colourants, permitted by the EU 94/36 guideline, were used: E 100 curcumin (CU), E 120 carminic acid (CA), E 150a caramel (CR), E 160a beta-carotene (BC), E 160g paprika-extract (PE) and E162 betanin (B). CA, B, BC and PE significantly increased the redness of batter, while BC, PE and CU increased (p<0.05) the yellowness. NaNO(2) decreased (p<0.05) the redness of batters in all treatments. Frankfurters with CA had the highest a* value followed by those with BC, PE and B. BC, PE and B increased the yellowness of frankfurters. NaNO(2) increased (p<0.05) the redness of frankfurters in all treatments. The storage of frankfurters for 4 weeks had no effect on redness and yellowness of frankfurters. Exposure either for 2 h in sunlight or for 4 h in artificial light had no significant effect on redness and yellowness of frankfurters from all treatments. Canned frankfurters (117 degrees ) with B had the greatest decrease in redness while those with BC the greatest increase in yellowness. Frankfurters with B were the most acceptable from the consumers according to their colour followed by those with PE. Frankfurters with B had also the highest score for overall acceptability, followed by those with CA and nitrites. By employing discriminant analysis on the data, equations were derived for the identification of the natural colourant used in the production of frankfurters. Results from frankfurters, produced with 0, 3.6, 14.4 and 28.8 mg of pure B kg and 100 and 150 mg/kg NaNO(2), have shown that the level of NaNO(2) can be reduced from 150 to 100 mg/kg with appropriate increase in B level and frankfurters with 14.4 mg B/kg were the most acceptable from the consumers according to their colour. PMID- 22062574 TI - The influence of meat pH on mechanical and sensory textural properties of dry cured ham. AB - The texture of dry-cured ham is one of the most important factors in consumer quality perception of the product. In this study the texture and mechanical properties of normal and Dark, Firm and Dry (DFD) dry-cured hams were studied as well as the relationship between them. DFD hams were softer, pastier, more crumbly and more adhesive than normal ones despite having lower non-protein nitrogen (p<0.05). One of the reasons for the texture characteristics of DFD hams could be the higher level of moisture observed in the Biceps femoris muscle and the high pH value. The mechanical parameters studied also showed clear differences between the two groups of hams, specially in the inner part which was less affected by the drying process. In general the correlation coefficients between sensorial and mechanical parameters were not very high (0.23-0.62). The use of a non-destructive mechanical test, compressing the ham with a spherical probe, makes it possible for DFD hams to be detected in the earlier stages of the manufacturing process and means that technological changes can be made in order to reduce the problematic texture obtained from this kind of meat. PMID- 22062575 TI - Freezing rate simulation as an aid to reducing crystallization damage in foods. AB - In food freezing processes the presence of large ice crystals is a serious drawback when a good final quality of the product is desired. To study the size and distribution of those crystals, a large piece of pork muscle has been frozen by liquid nitrogen evaporation. A mathematical model to simulate different cooling rates at the surface of the product was solved using a finite element method; this model satisfactorily fitted experimental data and predicted local freezing rates at different locations in the meat tissue. The model was applied to find the freezing rates that led to a good quality product, related to an optimum distribution of small ice crystals located inside and outside the tissue fibres. PMID- 22062576 TI - Refrigerated shelf life of vacuum-packaged, previously frozen ostrich meat. AB - Previously frozen ostrich meat was evaluated over 28 days to determine the refrigerated shelf life. Intact steaks and ground meat from three ostrich carcasses were vacuum-packaged, frozen to -40 degrees C for 5 days, and stored in a 0 degrees C walk-in cooler. Instrumental analysis of CIE L*a*b* values indicated that ostrich meat was very dark in color, initially and over time. Microbial growth stayed slightly below 1.0 * 10(7) CFU/g for up to 21 days of refrigerated storage. Sensorially evaluated color showed an increase (p <0.05) in darkness over time. Percentage of browning increased (p<0.05) over time from 1% initially to 55% for intact steaks and 75% for ground meat by 28 days. Sensory aroma scores significantly (p<0.05) changed over time, with unacceptable aroma occurring by 14 days. Previously frozen, vacuum-packaged ostrich meat stored under refrigerated conditions should be used within 10 days. PMID- 22062577 TI - Improvement of color and lipid stability of rabbit meat by dietary supplementation with vitamin E. AB - The effects of vitamin E (all-rac-alpha-tocopheryl acetate) supplementation on meat color and oxidative stability of muscle lipids in New Zealand White rabbits was determined. Twenty animals received pelleted diet (containing 60 mg/kg alpha tocopheryl acetate) and 10 of these (treatment group) received drinking water containing 100 mg alpha-tocopheryl acetate/L for 15 days before slaughter. The alpha-tocopherol content of the longissimus lumborum muscle (LL) was higher (5.66 vs 1.65 MUg/g) in the supplemented group than the control group (p<0.001). The surface redness (a*) of the muscle showed a significant time*treatment effect (p<0.001), decreasing more in the control group over 11 days of storage in the dark at +2.5 degrees C. The lightness (L*) showed a tendency (p=0.06) for a treatment*time effect. No effect of vitamin supplementation was observed on yellowness (b*). Thiobarbituric acid reactive substances (TBARS) in muscle, an index of oxidative stability, were lower in the treated than control group throughout storage (p<0.01 for treatment effect). Vitamin E supplementation appears to be an effective way to improve the color and lipid stability of rabbit meat. PMID- 22062578 TI - The relationship of sarcoplasmic and myofibrillar protein solubility to colour and water-holding capacity in porcine longissimus muscle. AB - In order to investigate the relationship of sarcoplasmic and myofibrillar protein solubility to colour and water-holding capacity (WHC) in pork, 60 loins were selected to represent the quality classes: PSE (pale, soft, exudative), RSE (reddish-pink, soft, exudative), RFN (reddish-pink, firm, non-exudative) and DFD (dark, firm, dry). PSE samples exhibited lower (p<0.05) protein solubility (sarcoplasmic, myofibrillar and total) compared to the other quality classes. RSE samples exhibited lower (p<0.05) sarcoplasmic protein solubility compared to DFD samples. RSE, RFN and DFD samples had similar myofibrillar and total protein solubilities. Sarcoplasmic protein solubility explained 71% of the variation in lightness with a linear decrease in L* value. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gels of the sarcoplasmic and myofibrillar samples distinctly showed the association of some sarcoplasmic proteins with the myofibrillar protein fractions in PSE and RSE samples. The sarcoplasmic proteins which precipitated were phosphorylase, creatine kinase, triose phosphate isomerase and myokinase for PSE and phosphorylase for RSE samples. Pork colour is highly correlated with precipitation of sarcoplasmic proteins while WHC is affected by denaturation of myofibrillar proteins (PSE samples) and lower ultimate pH (PSE and RSE samples). PMID- 22062579 TI - Consequences of packaging on bacterial growth. Meat is an ecological niche. AB - Meat is a good support for bacterial growth and particularly for bacteria which are specific of meat and meat products. Little is known about the physiological and biochemical factors which could explain why some bacterial species are only isolated from meat. This review tentatively points out, from an ecological point of view, some of these factors in Gram negative and Gram positive micro-organisms influencing storage life. PMID- 22062580 TI - Determination of lean meat in pig carcasses with the Autofom classification system. AB - A fully automatic classification equipment called Autofom for use at pig abattoirs has been developed and tested. It measures fat- and meat depth in carcasses by use of ultrasound. Measurement with Autofom is very fast (measuring up to 1250 carcasses per hour). It is non-invasive and low maintenance costs can be expected due to lack of moving parts. The repeatability and reproducibility have been estimated. An equation for calculating lean meat percentage on the basis of Autofom measurements has been calculated. The accuracy of the equation, expressed by residual mean square error and by standard error of prediction, is 1.84 and 1.95, respectively. A functionality test shows that, when installed on line at the abattoir, 99% of the carcasses can be classified by Autofom. The equipment will be a suitable alternative to automatic on-line determination of lean meat percentage in pig carcasses. PMID- 22062581 TI - Development of meat and carcass quality characteristics in Iberian pigs reared outdoors. AB - A study of age-related changes in carcass traits and meat quality characteristics of Longissimus dorsi (LD) and Biceps femoris (BF) of free-ranged Iberian pigs was carried out to check whether the slaughter age used in the traditional management system of Iberian pigs is adequate. There was a great increase in live and carcass weight during fattening, principally due to an increase in fat deposition, as could be deduced from the percentage of dissectible fat and the backfat thickness. However, intramuscular fat in LD and BF showed only slight changes during the fattening. Myoglobin content tended to increase throughout lifetime in both muscles, whereas water-holding capacity decreased in intermediate ages and showed the highest values in the oldest animals. Total collagen content did not vary during lifetime; on the other hand, insoluble collagen increased from 7 to 77% of total collagen. It can be concluded that the traditional management system of Iberian pigs can be improved by fattening the pigs at a younger age, without negative consequences on the meat quality. PMID- 22062582 TI - Influence of aromatic components from pig manure on odour and flavour of cooked chicken meat. AB - An experiment with 96 broilers distributed across six treatments was carried out. Each treatment consisted of four cages each with four broilers. The six treatments were: the control (treatment 1), broilers placed in cages with a welded wire bottom hanging over smelling pig manure (treatment 2), or placed on a pig manure mat (treatment 3), combined with two intervals, i.e. 1 week (group a) and 2 weeks (group b) before slaughter. The content of skatole in the abdominal fat was measured, and the odour and flavour impressions after cooking were evaluated by a taste panel. The treatments were compared with two control treatments: broilers produced traditionally in cages either without (treatment 1a) or with (treatment 1b) contact with their own manure for a fortnight. A higher skatole level in abdominal fat of broilers in physical contact with pig manure (treatment 3) was measured, compared with broilers without physical contact with pig manure for at least 1 week (treatments 1 and 2) (p<0.05). The consumer taste panel evaluation was not affected by the fact that the broilers had been lying on pig manure. However, the evaluation of the odour of the cooked meat, when opening the cooking bag, was to some extent negatively affected by the experimental treatments of broilers, which had physical contact with the pig manure (p<0.05). Furthermore, physical contact with the manure, regardless of whether it was broiler or pig manure, proved to affect the odour of the meat (p<0.01). For broilers placed in cages without physical contact with the pig manure (treatments 2a and 2), the smell had no negative influence on either the odour or on the flavour of the meat, and the content of skatole was not different from that of the broilers on the control treatment. A taste panel evaluation performed on four broilers of the treatments 1a, 2b, and 3b showed no flavour differences among treatments. Whether the broilers had been exposed to a given treatment for 1 or 2 weeks made no difference, either to the skatole concentration or to the odour or flavour impression of the newly cooked chicken meat. PMID- 22062583 TI - Effects of electrical and mechanical stunning methods on meat quality in ostriches. AB - The effect of electrical and captive needle air pressure stunning methods on some meat quality parameters was examined in ostriches under practical conditions. One hundred and fifteen ostriches were used in three experiments. The ostriches were stunned either electrically (head only) or by using a captive needle with air pressure. In the first experiment the ostriches were stunned at 90 V (~effectively 52 V), 200 V and by captive needle using air pressure. In the second experiment voltages of 175 and 200 V were applied and a captive needle stunning method using air pressure. In the third experiment the birds were stunned at 175 V with a short stun/stick interval. Experiments 2 and 3 were performed in a different slaughterhouse from experiment 1. Meat quality was assessed by measuring the pH, temperature and colour at 45 min and 18 h post mortem and by determining water binding capacity and haemorrhage score at 18 h post mortem in the big drum, tender loin and triangular filet muscles. The measured stunning parameters in the first experiment were 204+/-96 mA (~52 V) during 11+/-1 s and 556+/-85 mA (~200 V) during 6+/-0 s. The stun/stick interval was 136+/-38 s. The rigor mortis value in the tender loin and both pH(1) and pH(2) in the big drum, tender loin and triangular filet muscles were (p<0.05) lower when stunned with air pressure compared with electrical stunning. Moreover internal light scattering remained higher. The measured currents in the second experiment were 561+/-226 mA (~173 V) during 6+/-2 s and 518+/-120 mA (~200 V) during 6 s. The stun/stick interval was 39+/-12 s. The pH at 45 min and 18 h differed (p<0.05) in the tender loin and triangular filet muscles as did the temperature at 45 min in the three muscles between the different stunning groups. The stunning in the third experiment was carried out with 548+/-180 mA during 6+/ 2 s. The stun/stick interval was 5+/-2 s. After the short stun/stick interval the pH(2) was lower (p<0.05) for the tender loin and triangular filet muscles and the wetness of the filter paper of the big drum was (p<0.05) lower compared with the other groups. Our experiments showed that stunning methods affected several meat quality parameters. Using a high electrical stunning current, captive needle stunning or a short stun/stick interval may positively affect some parameters. More research is necessary to examine effects of pre slaughter handling on meat quality. PMID- 22062584 TI - Reduction in cadmium exposure in the United States population, 1988-2008: the contribution of declining smoking rates. AB - BACKGROUND: Public health policies such as tobacco control, air pollution reduction, and hazardous waste remediation may have reduced cadmium exposure among U.S. adults. However, trends in urine cadmium, a marker of cumulative cadmium exposure, have not been evaluated. OBJECTIVES: We estimated the trends in urine cadmium concentrations in U.S. adults using data from the National Health and Nutrition Examination Surveys (NHANES) from 1988 to 2008. We also evaluated the impact of changes in the distribution of available cadmium determinants (age, sex, race, education, body mass index, smoking, and occupation) at the population level to explain cadmium trends. METHODS: The study population included 19,759 adults >= 20 years of age with measures of urine cadmium and cadmium determinants. RESULTS: Age-adjusted geometric means of urine cadmium concentrations were 0.36, 0.35, 0.27, 0.27, 0.28, 0.25, and 0.26 ug/g creatinine in 1988-1991, 1991-1994, 1999-2000, 2001-2002, 2003-2004, 2005-2006, and 2007 2008, respectively. The age, sex, and race/ethnicity-adjusted percent reduction in urine cadmium geometric means comparing 1999-2002 and 2003-2008 with 1988-1994 were 27.8% (95% confidence interval: 22.3%, 32.9%) and 34.3% (29.9%, 38.4%), respectively (p-trend < 0.001), with reductions in all participant subgroups investigated. In never smokers, reductions in serum cotinine accounted for 15.6% of the observed reduction. In ever smokers, changes in smoking cessation, and cumulative and recent dose accounted for 17.1% of the observed reduction. CONCLUSIONS: Urine cadmium concentrations decreased markedly between 1988 and 2008. Declining smoking rates and changes in exposure to tobacco smoke may have played an important role in the decline of urine cadmium concentrations, benefiting both smokers and nonsmokers. Cadmium has been associated to several health outcomes in NHANES 1999-2008. Consequently, despite the observed decline, further reduction in cadmium exposure is needed. PMID- 22062585 TI - Expression, purification, and characterization of recombinant NOD1 (NLRC1): A NLR family member. AB - NOD1 (NLRC1) is a member of the NLR family of innate immunity proteins, which are important cellular sensors of various pathogens. Deregulated NOD1 signaling is involved in various autoimmune, inflammatory, and allergic diseases, making it a potential target for drug discovery. However, to date, the successful high-yield purification NOD1 protein has not been reported. Here we describe the large-scale expression of recombinant NOD1 protein in non-adherent mammalian cells. One-step immunoaffinity purification was carried out, yielding highly pure protein with excellent yields. Gel-sieve chromatography studies showed that the purified NOD1 protein eluted almost exclusively as a monomer. Addition of the NOD1 ligand (gamma-Tri-DAP) stimulated NOD1 protein oligomerization. Using purified NOD1 protein for nucleotide binding studies by the Fluorescence Polarization Assay (FPA) method, we determined that NOD1 binds preferentially to ATP over ADP and AMP or dATP. We also documented that purified NOD1 protein binds directly to purified pro-apoptotic protein Bid, thus extending recent data that have identified Bid as an enhancer of NOD1 signaling. This expression and purification strategy will enable a wide variety of biochemical studies of mechanisms of NOD1 regulation, as well as laying a foundation for future attempts at drug discovery. PMID- 22062586 TI - Feasibility of flowcytometric quantitation of immune effector cell subsets in the sentinel lymph node of the breast after cryopreservation. AB - The sentinel lymph node (SLN) is an emerging focus for immunological research in breast cancer. Cryopreservation of SLN single-cell suspensions allows for simultaneous phenotypic multi-parameter analyses and minimizes operator dependent variability. This is of particular importance for immunomonitoring of large multicenter trials. However, little data are available regarding the influence of cryopreservation on phenotypic characteristics of lymph node dendritic cells and T cells. In this study we assessed the feasibility of cryopreservation of viable SLN cell samples for flowcytometric analysis, by comparing quantitative analyses of SLN cell samples after freeze-thawing with direct analysis of fresh SLN cell samples. SLN were collected from nine breast cancer patients. From each SLN cell sample, half was used for immediate analysis and half was analyzed after cryopreservation and thawing. Conventional dendritic cell (cDC) and T cell subsets were quantified and phenotypically characterized by flow cytometry. The observed frequencies of both CD1a(+) and CD1a(-)CD11c(+)CD14(-) cDC subsets showed significant correlation between the fresh and frozen-thawed samples. Similar high correlations were found for CD83 and CD86 expression markers on the more frequent (>0.2%) CD1a(+) and CD1a(-)CD11c(+)CD14(-) cDC subset, but not on the low-frequency (<0.2%) CD1a(+)CD11c(+)CD14(+) cDC subset. CD4/CD8 T cell ratios were comparable and were significantly correlated pre- and post-freezing. Regulatory CD4(+)CD25(hi) T cell frequencies and their FoxP3 expression levels were significantly higher after freezing-thawing than in the freshly analyzed samples. Nevertheless, a highly significant correlation was found for both parameters pre- and post-freezing. Cryopreservation and thawing seems a valid and practical alternative to direct analysis of fresh viable lymph node cells, without introducing cryo-dependent variance between SLN samples. However, enumeration of low-frequency cell populations and assessment of their marker expression levels are less reliable after cryopreservation and should be assessed and considered in the design of each clinical trial. PMID- 22062587 TI - Development and implementation of a three-choice serial reaction time task for zebrafish (Danio rerio). AB - Zebrafish are an established and widely utilized developmental genetic model system, but limitations in developed behavioral assays have meant that their potential as a model in behavioral neuroscience has yet to be fully realized. Here, we describe the development of a novel operant behavioral assay to examine a variety of aspects of stimulus control in zebrafish using a 3 choice serial reaction time task (3 CSRTT). Fish were briefly exposed to three spatially distinct, but perceptually identical stimuli, presented in a random order after a fixed-time inter-trial interval (ITI). Entries to the correct response aperture either during the stimulus presentation, or within a brief limited hold period following presentation, were reinforced with illumination of the magazine light and delivery of a small food reward. Following training, premature responding was probed with a long-ITI session three times; once at baseline, once following a saline injection and once following an injection of a low dose of amphetamine (AMPH; 0.025 mg/kg). We predicted that if premature responding was related to impulsivity (as in rodents) it would be reduced following the AMPH injection. Results confirmed that zebrafish could learn to perform a complex operant task similar to tasks developed for rodents which are used to probe sustained attention and impulsivity, but the results from the AMPH trials were inconclusive. This study provides the foundations for development and further validation of this species as a model for some aspects of human attentional and impulse control disorders, such as substance abuse disorder. PMID- 22062588 TI - Local delivery of IL-2 reduces atherosclerosis via expansion of regulatory T cells. AB - OBJECTIVE: Recent studies indicate that regulatory T cells (Tregs) attenuate murine atherosclerosis. Since interleukin (IL)-2 induces Tregs proliferation, we tested the impact of L19-IL2, a fusion antibody specific to extra-domain B of fibronectin (ED-B) containing an active human IL-2 molecule, in experimental atherosclerosis. METHODS AND RESULTS: L19-IL2 or appropriate controls were given intravenously to 6 month old Western diet-fed apoE(-/-) mice on day 1, 3, and 5. Human IL-2 was detected on day 7 within atherosclerotic plaques of L19-IL2 treated mice, and magnetic resonance imaging of the plaques showed a significant adventitial gadolinium enhancement on day 7 and 13, suggesting microvascular leakage as a result of the pharmacodynamic activity of L19-IL2. Treatment with L19-IL2 significantly reduced the size of pre-established atherosclerotic plaques at the thoracic aorta (Sudan III stained area) and in the aortic root area (microscopic, morphometric analysis) on day 7 as compared to controls (L19, D1.3 IL2, NaCl) as well as compared to baseline (day 0). Tregs markers Foxp3 and CTLA4 were highly increased in plaques after L19-IL2 treatment compared to controls (p<0.01), whereas the macrophage marker Mac3 was significantly reduced (p<0.03). Co-treatment with IL-2-receptor blocking antibody PC61 abrogated L19-IL2-induced plaque reduction compared with IgG control (p<0.03). CONCLUSION: L19-IL2 delivers functional IL-2 to pre-established atherosclerotic plaques of WD-fed apoE(-/-) mice resulting in significant plaque size reduction mediated by local Tregs. PMID- 22062589 TI - HDL-cholesterol and prediction of coronary heart disease: modified by physical fitness? A 28-year follow-up of apparently healthy men. AB - OBJECTIVE: High-density lipoprotein cholesterol (HDL) and physical fitness (PF) have both been shown to predict cardiovascular disease (CVD), particularly coronary heart disease (CHD). Increased PF is associated with increased HDL and may partly explain the benefit of HDL. We tested the hypothesis that PF influences the prognostic impact of HDL for CHD and also for CHD-, CVD- and all cause death. METHODS: HDL was measured 1979-1982 in 1357 healthy men aged 44-69 years followed up to 28 years. PF was measured using bicycle exercise test. Hazard ratios (HRs) adjusted for age, smoking, systolic blood pressure, and total cholesterol and further for PF between HDL quartiles were calculated using Cox proportional survival model. RESULTS: The highest HDL quartile was associated with lower risk of CHD (HR: 0.57, 95% confidence interval [CI]: 0.43-0.74), fatal CHD (HR: 0.56, CI: 0.36-0.86), fatal CVD (HR: 0.64, CI: 0.46-0.88) and all-cause death (HR: 0.80, CI: 0.65-0.99) compared to the lowest quartile. Adjustments for PF or changes in PF over 8.6 years did not change the results except for all cause death, which was not significantly different between HDL quartiles. We found no interaction between HDL and PF. CONCLUSIONS: HDL is a strong predictor of long term risk of CHD, fatal CHD and fatal CVD in healthy middle-aged men. Physical fitness or its changes had no impact on the ability of HDL to predict CHD. PMID- 22062590 TI - Immune-modulation by polyclonal IgM treatment reduces atherosclerosis in hypercholesterolemic apoE-/- mice. AB - OBJECTIVE: Gamma-globulin treatment reduces experimental atherosclerosis by modulating immune function; however the effect of IgM on atherosclerosis is not known. We investigated the effect of serum-derived, non-immune polyclonal IgM (Poly-IgM) on atherosclerosis in mice with advanced disease and also assessed its immune-modulatory effects. METHODS AND RESULTS: Aortic atherosclerosis was assessed in apoE-/- mice fed atherogenic diet starting at 6 weeks of age. In addition, mice were also subjected to perivascular cuff injury to the carotid artery at 25 weeks of age to induce accelerated atherosclerosis. At the time of injury, the mice were treated weekly with a commercially available Poly-IgM (0.4mg/mouse) or PBS for 4 weeks and euthanized at 29 weeks of age. Poly-IgM reduced aortic atherosclerosis, and reduced lesion size in the aortic sinus and injured carotid artery, without significant changes in serum cholesterol levels. Poly-IgM treatment was associated with increased anti-oxLDL IgG titers and a reduction in the % splenic CD4(+) T cells compared to controls. The splenic CD4(+) T cell cultured from the Poly-IgM treated mice had reduced proliferation in vitro compared with controls. CONCLUSION: Poly-IgM treatment reduced aortic and accelerated carotid atherosclerosis in apoE-/- mice in association with increased anti-oxLDL IgG titers, and reduced number and proliferative function of splenic CD4(+) T cells. Our study identifies a novel athero-protective and immunomodulatory role for non-immune polyclonal IgM. PMID- 22062591 TI - Isolated troponin increase after percutaneous coronary interventions: does it have prognostic relevance? AB - Percutaneous coronary intervention (PCI) is often "associated" with myocardial injury. This event has been considered in the past as an acceptable trade-off for an optimal stent deployment. More recently, in the Universal Definition of myocardial infarction (MI), an increase of either cardiac troponins or creatine kinase-MB >3 times the upper reference limit (URL) has been defined as MI. Although there is no doubt on the accuracy of cardiac troponins in the diagnosis of spontaneous MI, existing data do not support the hypothesis that an isolated elevation of cardiac troponins over such threshold is associated with an adverse prognosis after PCI. PMID- 22062592 TI - Development of shelf stable pork sausages using hurdle technology and their quality at ambient temperature (37+/-1 degrees C) storage. AB - Shelf stable pork sausages were developed using hurdle technology and their quality was evaluated during ambient temperature (37+/-1 degrees C) storage. Hurdles incorporated were low pH, low water activity, vacuum packaging and post package reheating. Dipping in potassium sorbate solution prior to vacuum packaging was also studied. Reheating increased the pH of the sausages by 0.17units as against 0.11units in controls. Incorporation of hurdles significantly decreased emulsion stability, cooking yield, moisture and fat percent, yellowness and hardness, while increasing the protein percent and redness. Hurdle treatment reduced quality deterioration during storage as indicated by pH, TBARS and tyrosine values. About 1 log reduction in total plate count was observed with the different hurdles as were reductions in the coliform, anaerobic, lactobacilli and Staphylococcus aureus counts. pH, a(w) and reheating hurdles inhibited yeast and mold growth up to day 3, while additional dipping in 1% potassium sorbate solution inhibited their growth throughout the 9 days storage. Despite low initial sensory appeal, the hurdle treated sausages had an overall acceptability in the range 'very good' to 'good' up to day 6. PMID- 22062593 TI - Effect of enhancement and ageing on flavor and volatile compounds in various beef muscles. AB - To identify and quantify selected flavor-active volatile compounds and relate them to sensory characteristics, the gluteus medius (round), rectus femoris (round), vastus lateralis (round), vatsus medialis (round), teres major (chuck), infraspinatus (chuck), complexus (chuck), serratus ventralis (chuck), psoas major (loin) and longissimus dorsi (loin) were removed from heifer carcasses, enhanced, vacuum packaged, aged for 7 or 14days, steaks were cut, vacuum packaged and frozen (48h). Flavor-active volatiles affected by enhancement and ageing in the various muscles included nonanal, 2,3-octanedione, pentanal, 3-hydroxy-2 butanone, 2-pentyl furan, 1-octen-3-ol, butanoic acid, pentanal and hexanoic acid, compounds often associated with lipid oxidation. Enhancement decreased hexanal and hexanoic acid. Ageing decreased butanoic acid. Pentanal content varied among muscles depending on enhancement and ageing. Livery off-flavor was positively correlated with pentanal, hexanal, 3-hydroxy-2-butanone and hexanoic acid. Rancid off-flavor was correlated with pentanal and with 2-pentyl furan but not with hexanal. PMID- 22062594 TI - Meat quality of Nguni, Bonsmara and Aberdeen Angus steers raised on natural pasture in the Eastern Cape, South Africa. AB - The current study compared meat quality of Nguni, Bonsmara and Angus steers raised on natural pasture. Fifteen seven-month-old weaners of each breed were kept at the University of Fort Hare Farm for 12 months till slaughter. Monthly weights of the steers were recorded. Carcasses were electrically stimulated. The m. longissimus thoracis et lumborum was sampled for the measurement of meat colour, pH, drip loss, sarcomere length, myofibrillar fragmentation length and Warner Bratzler (WB) shear force. The Nguni had the highest (P<0.05) average daily gain. Bonsmara and Angus steers had higher (P<0.05) carcass weight and dressing percentage than the Nguni steers. Meat quality characteristics were similar among all the breeds except that Nguni meat was darker (L(*)) (P<0.05) than meat from the other two breeds. The respective L(*) values for Nguni, Bonsmara and Angus steers were 36.5, 38.6 and 39.9. There were significant (P<0.05) correlations among some meat quality traits. There were significant (P<0.05) correlations between WB values of meat aged for 2 and 21 days in Nguni and Bonsmara, but not in Angus. Meat quality from Nguni compares favourably with that from established breeds, when raised on natural pasture. PMID- 22062595 TI - Effect of the inoculation of a starter culture and vacuum packaging (during resting stage) on the appearance and some microbiological and physicochemical parameters of dry-cured ham. AB - The effect of the inoculation of a starter culture and vacuum packaging (during the resting stage) on dry-cured ham appearance, microbiological and physicochemical parameters was studied. Half of the 36 processed hams were inoculated, after salting, with a commercial starter culture containing lactic acid bacteria, Gram-positive catalase-positive cocci and yeasts. 18 hams per group (inoculated and non-inoculated) remained vacuum packaged during resting. Microbiological analyses were carried out on the lean surface during processing, on subcutaneous fat tissue at the drying stage and on lean tissue in the finished product. Appearance was evaluated during processing. Physicochemical analyses (NaCl, H(2)O, proteolysis index, a(w)) were done on Semimembranosus and Biceps femoris in the final product. Inoculation caused a reduction of mould growth and oil drip. Vacuum packaging induced increased proteolysis and increases in all microbial counts and a reduction of oil drip, mould growth and weight loss during processing. PMID- 22062596 TI - Proteolysis in biceps femoris during Jinhua ham processing. AB - Sixty experimental Jinhua hams were processed by a traditional method. The nitrogen fractions and free amino acids in biceps femoris were analyzed. Intense proteolysis was found in ham muscle and totally more than 10% of muscle proteins were degraded during the course of Jinhua ham processing. The proteolytic index of Jinhua ham was between 14 and 20. Both insoluble and soluble proteins were degraded to some degree and the later showed more intense degradation. In the soluble fraction, the percentage of non-protein nitrogen (NPN) increased gradually whereas that of protein nitrogen decreased during processing (P<0.05). However, very small amount of peptides larger than 1kDa was accumulated during the whole course of processing, which proved that intense degradation reactions were also happened to them, especially at the post ripening stage when dramatic decrease of nitrogen fraction from all the peptides larger than 1kDa was found. As a result, more than 90% of the NPN products from muscle proteolysis were free amino acids and peptides of MW less than 1kDa that might make important contribution to Jinhua ham taste and provide precursors for the generation of volatile flavor compounds in ham muscle. The pattern of muscle proteolysis coincided with the reported changes of muscle proteolytic enzymes during processing, seemingly indicating that the enzymes could have played important roles in ham muscle proteolysis. PMID- 22062597 TI - Progress in reducing the pale, soft and exudative (PSE) problem in pork and poultry meat. AB - Research in the area of the pale, soft and exudative (PSE) pork and poultry meat is reviewed in this article with an emphasis on genetic, biochemical and metabolic factors contributing to the problem. Over the past five decades, there has been much more work in the pork meat area where a few genetic markers have been identified, and are currently used to remove susceptible animals from the herd. Some of the markers are linked to aberrant calcium regulation in the early postmortem muscle. The poultry industry is still not at the point of using genetic marker(s); however, some recent work has revealed several potential markers. The review also discusses environmental factors such as antemortem stress and early postmortem processing practices (e.g. chilling rate) that can influence the development and severity of the PSE phenomenon. Some of these factors are known to cause protein denaturation at the early stage of postmortem and directly contribute to poor water-holding capacity and inferior texture in fresh meat and later in processed products. A newer hypothesis suggesting that variation in protein oxidation, in response to antemortem stress and early postmortem tissue environment, can contribute to development of PSE pork is also discussed. Finally, a few recommendations for future work are proposed. PMID- 22062598 TI - Effects of temperature conditioning on postmortem changes in physico-chemical properties in Korean native cattle (Hanwoo). AB - The objective of this study was to examine the changes in physico-chemical properties that occur after adjusting postmortem chilling temperatures in Hanwoo beef. The right sides of beef carcasses were chilled for 4h at 2 degrees C, 4h at 12 degrees C and 16h at 2 degrees C. The left sides were used as controls, chilled for 24h at 2 degrees C. It took 8h for the control carcasses to cool down to <10 degrees C and 10h 20min for the treatment. Adjusting the chilling temperature could be effective in lowering the postmortem pH and glycogen content. Treatment muscles at least 8h postmortem had longer sarcomeres than the control (P<0.05). The shear force in treatment carcasses at day 1 was similar to that of the control at day 6. Alternate chilling temperature had no detrimental effect on drip, cooking, total loss or color. Total numbers of aerobic plate counts were not significantly different between the control and treatment. PMID- 22062599 TI - Effect of exercise on skeletal muscle proteolytic enzyme activity and meat quality characteristics in Iberian pigs. AB - The effects of physical activity on performance, carcass traits, Psoas major lysosomal and exoprotease acitivies and meat quality were studied in 24 castrated male Iberian pigs during the last fattening period (from 111.1+/-SD: 5.2kg). Pigs were randomly distributed in three groups. Two groups receiving the same diet were reared in confinement, one housed in individual pens of 8m(2) (sedentary group) and the other was housed outdoor with daily (up to 2km) forced walking (exercise group). And one group was reared under the traditional production system walking daily several km and fed mostly with acorn from Quercus ilex and Quercus rotundifolia and grass (free-range group). No differences were found in performance and carcass traits. In exercised pigs a lower activity of cathepsin B+L and total cathepsins (P<0.05) was observed. Exercise induced the inhibition of dipeptidyl peptidases II and III and arginyl aminopeptidase and the activation of dipeptidyl peptidases IV and leucyl aminopeptidase (P<0.05). Although no effects on total free amino acids in Psoas major muscle were observed the concentration of branched chain amino acids decreased in the free-range pig group probably related to an increase in physical activity. Exercise had no effects in Psoas major postmortem tenderness and water holding capacity. PMID- 22062600 TI - In vitro study to evaluate the degradation of bovine muscle proteins post-mortem by proteasome and MU-calpain. AB - The degradation of bovine muscle proteins by proteasome and ubiquitous calpains was explored via 2D gel proteome analysis by inhibition of the physiological level of the proteases by specific inhibitors. The inhibition of the proteasome chymotrypsin- and trypsin-like activity results in the lack of degradation of several fragments of structural proteins such as actin, troponin T, myosin light chain and nebulin. In addition the degradation of several sarcoplasmatic proteins was eliminated when proteasome was inhibited. The inhibition of the ubiquitous calpain only resulted in minor changes in the degradation pattern, which might indicate that p94, which is not inhibited by calpastatin, is involved in the degradation post-mortem. The results of the present study indicate a sequential degradation of the structural proteins post-mortem, where calpain initiates the disruption and destabilisation of the myofibrillar structure, and thereby allows the proteasome to act. PMID- 22062601 TI - Energy supply patterns for finishing steers: Feed conversion efficiency, components of bodyweight gain and meat quality. AB - The objective was to determine the effect of pre-slaughter growth rate on feed efficiency, components of body growth and on the tenderness of longissimus muscle from steers reared to a common age and carcass weight. Sixty Friesian steers were group-housed and offered grass silage ad libitum and 3.5kg concentrates per animal daily for 5 months and then 5kg concentrates and 1kg grass hay for 1month before the experiment began. The animals were then weighed and in a randomised block were assigned to one of 5 groups, for slaughter at the beginning of the experiment or to be offered concentrates and hay (900 and 100g/kg total diet, respectively) to achieve target growths of: 0.72kg/day continuously for 17 weeks, 0.36kg/day for the first 8 weeks and 1.08kg/day for the final 8 weeks (low-high), 1.08kg/day for the first 8 weeks and 0.36 for the final 8 weeks (high-low) or 0.36kg/day for the first 2 weeks, 0.72kg/day during weeks 4 and 14 and 1.08kg/day for the final 2 weeks (pulse). One week was allowed for transition to the different dietary allowances within each energy supply pattern. The mean age at the beginning and end of the study was 18 and 22.5 months, respectively. After slaughter, the weight of the carcass and kidney+channel fat depot were recorded, the pistola hind quarter was dissected into fat, lean and bone and the tenderness of the m. longissimus thoracis et lumborum (LTM) muscle was measured instrumentally and using a trained taste panel after 2, 7 or 14 days ageing. The pattern of energy supply did not affect carcass weight, fat score or kidney+channel fat weight. The pistola hind quarter from animals offered the low high energy pattern had a similar composition to the continuously-fed animals but contained more muscle than that from animals offered high-low or pulse energy patterns. After 14 days ageing, LTM from the continuously-fed animals was more tender than that from animals offered the other energy supply patterns but shear force did not differ between supply patterns. The data do not support the hypothesis that pre-slaughter growth rate increases tenderness but suggest that energy supply pattern can influence body composition of finishing cattle. PMID- 22062602 TI - Eating quality of young bulls from three Spanish beef breed-production systems and its relationships with chemical and instrumental meat quality. AB - Sensory characteristics of longissimus thoracis muscle from three local Spanish beef breed-production systems and their relationships with chemical and instrumental meat quality traits were studied. Young bulls of Bruna dels Pirineus (BP; n=69), Avilena-Negra Iberica (A-NI; n=70) and Morucha (MO; n=70) breeds were reared in their own production systems. MO breed showed the highest water holding capacity and also the highest thawing loss and haem pigment content (P<0.001). No differences in moisture and protein contents were found among breeds. A-NI showed the highest intramuscular fat (IMF, P<0.05) and total collagen (P<0.001) contents, whereas BP showed the lowest IMF content (P<0.05) and the highest collagen solubility (P<0.001). Beef flavour, tenderness and juiciness accounted for the eating quality differences among the three breed-production systems. Meat from A-NI was rated significantly higher (P<0.01) for beef flavour and tenderness than that from BP and MO animals. Furthermore, MO showed the lowest juiciness (P<0.001) which could be due to its higher thawing loss. Within the three breeds, thawing loss was negatively correlated with juiciness and, likewise cooking loss with juiciness and tenderness (P<0.05). The canonical discriminant analysis showed that the three breeds were significantly different (P<0.05) from each other according to sensory attributes, which justifies their involvement in different protected geographical indications (PGI). PMID- 22062603 TI - Muscularity and eating quality of lambs: Effects of breed, sex and selection of sires using muscularity measurements by computed tomography. AB - Differences in muscularity of the hind leg (HL) and lumbar region (LR) were investigated between sexes (ram vs ewe lambs), breeds (Scottish Blackface, SBF vs Texel, TEX) and progeny of high- and low-muscularity sires (HM, LM) (n=471). The influence of these factors on meat eating quality (MEQ) was also examined (n=229). TEX lambs had 16% greater muscularity than SBF in both regions, whilst differences between sire groups were 4%. Ewe lambs had slightly higher values of muscularity for the HL than rams, but values were similar for the LR. Meat from SBF lambs had higher tenderness, stronger lamb flavour and higher overall liking than TEX meat. Sex had a weak influence with ram lambs having a stronger abnormal flavour and lower overall liking in the LR only. No significant differences in MEQ were found between HM- and LM-sired lambs, suggesting that improvements in muscularity would not have unfavourable effects on MEQ. PMID- 22062604 TI - Muslim consumer trust in halal meat status and control in Belgium. AB - This paper focuses on public trust of Belgian Muslims in information sources of halal meat and their confidence in key actors and institutions for monitoring and controlling the halal meat chain. Cross-sectional consumer data were collected through a survey with 367 Muslims during the summer of 2006 in Belgium. Findings reveal that Islamic institutions and especially the Islamic butcher receive in general most confidence for monitoring and controlling the halal status of meat, and for communicating about halal meat. However, based on Muslims' confidence, four distinct market segments were identified: indifferent (29.1%), concerned (9.7%), confident (33.1%) and Islamic idealist (26.7%). These segments differ significantly with respect to trust in information sources and institutions, health and safety perception of halal meat, perceived halal meat consumption barriers, behavioural variables (halal meat consumption frequency and place of purchase), and socio-cultural (acculturation and self-identity) and individual characteristics. Indifferent consumers are rather undecided about who should monitor the halal status of meat, and they are most open to purchasing halal meat in the supermarket. Concerned Muslim consumers display higher confidence in Belgian than in Islamic institutions, which associates with perceiving a lack of information, poor hygiene and safety concern as barriers to purchasing halal meat. Confident consumers display a clear preference for Islamic institutions to monitor and communicate about halal. Islamic idealists, who are typified by younger age, second generation and high Muslim self-identity, differ from the confident consumers through their very low confidence in local Belgian sources and institutions. PMID- 22062605 TI - Water-soluble precursors of beef flavour: I. Effect of diet and breed. AB - The effects of diet and breed on the concentration of water-soluble flavour precursors, namely sugars, free amino acids, ribonucleotides, creatinine, carnosine and creatine, were studied in beef longissimus lumborum muscle. Diet had a significant effect on the concentration of free amino acids, with animals fed on grass silage having higher free amino acid levels than animals fed on a concentrate diet, whereas animals fed concentrates had a higher total reducing sugar content. Differences between a beef breed (Aberdeen Angus*Holstein Friesian) and a dairy breed (Holstein-Friesian) were generally small. PMID- 22062606 TI - A comparison of the physicochemical and sensory characteristics of alheira samples from different-sized producers. AB - Alheira is a traditional Portuguese meat product made from boiled meat, usually pork and/or poultry, and bread. The physicochemical and sensory properties of alheira were analyzed to determine the relationships between them and to evaluate how they are affected by the product's origin i.e. if is produced on a small or industrial scale. The most important variables used to characterize alheira are: color, visual evaluation of the amount of meat and bread, paprika aroma, clamminess and fibrousness, water activity, moisture, fat, carbohydrate content, hardness and color parameters (L(*),a(*), and b(*)). Principal component analysis demonstrated that drying has a major effect on these characteristics, as it plays a part in the product's physical make-up. Using these parameters it was possible to ascertain that industrial products enjoyed higher levels of consumer acceptability, given that they contain a higher proportion of meat and undergo a shorter drying process. PMID- 22062607 TI - Development and validation of a probabilistic second-order exposure assessment model for Escherichia coli O157:H7 contamination of beef trimmings from Irish meat plants. AB - A second-order quantitative Monte Carlo simulation model was developed for Escherichia coli O157:H7 contamination of beef trimmings in Irish abattoirs. The assessment considers initial contamination levels, cross-contamination and decontamination events during the cattle slaughter process. The mean simulated prevalence of E. coli O157:H7 on trimmings was 2.36% and the mean simulated counts of E. coli O157:H7 on contaminated trimmings was -2.69log(10)CFU/g. A parallel validation survey provided some confidence in the model predictions. An uncertainty analysis indicated that microbial test sensitivity is a significant factor contributing to model uncertainty and requires further investigation while also indicating that risk reduction measures should be directed towards reducing the hide to carcass transfer (correlation coefficient 0.25) during dehiding and reducing the initial prevalence and counts on bovine hides (correlation coefficients 0.19 and 0.16, respectively). A characterisation of uncertainty and variability indicating that further research is required to reduce parameter uncertainty and to achieve better understanding of microbial transfer in meat plants. The model developed in this study highlights the need for further development of quantitative risk assessments in the food industry. PMID- 22062608 TI - Biomechanical and microbiological changes in natural hog casings treated with ozone. AB - The objective of this study was to determine the biomechanical and microbiological effects of exposing natural hog casings to ozonated water ~7mg/l for 0, 2 or 4h at 16 degrees C. A total of 450 casing segments representing 10 hanks were used over five testing days and arranged in a randomized block split plot design. For each treatment, pH, temperature, actual ozone concentration, bursting strength, maximum rupture force, and L(*), a(*) and b(*) color space values were determined. The bursting strength and the maximum rupture force values suggested that casings can be treated by ozone up to 2h without deterioration. After ozone treatments, changes in L(*), a(*) and b(*) color space values made the casings appear lighter than the control samples. Microbiological studies showed that 1 and 2h ozonation reduced counts of Escherichia coli biotype I, which expressed green fluorescent protein, by 0.4 and 0.6log(10)CFU/25.4cm casing, respectively. PMID- 22062609 TI - The effects of broiler catching method on breast meat quality. AB - Mechanical and hand catching of broilers (n=24 per treatment for each trial) were performed to determine if differences existed in breast meat quality among catching methods. Two trials (summer and winter 2005) were conducted, and it was determined that there was greater variation in meat quality in the summer in comparison to the winter within treatments in both catching methods. Neither catching method yielded breast meat with significant quality issues. Therefore, either catching method should be acceptable for catching broilers in respect to meat quality. However, mechanical catching and crating for 2h yielded slightly better (P<0.05) quality meat than hand catching in respect to averages and individual quality problems. These slight improvements in meat quality included higher (P<0.05) 15min pH, lower (P<0.05) drip loss, and lower (P<0.05) incidence of pale meat with a rapid pH decline in the summer. PMID- 22062610 TI - Analysis of volatile compounds of Iberian dry-cured loins with different intramuscular fat contents using SPME-DED. AB - In order to study the effect of both, ripening time and IMF content on the volatile profile of Iberian dry-cured loin, volatile compounds from the headspace of 10 Iberian dry-cured loins with different intramuscular fat contents (IMF), low (average IMF content of 2.3%) and high (average IMF content of 6.7%), at days 40 and 55 of the ripening process were analysed using SPME coupled to a direct extraction device (DED) and subsequent gas chromatography/mass spectrometry (GC/MS). Chromatographic areas of the main chemical families detected (hydrocarbons, aldehydes, alcohols, ketones and acids) increased with ripening time. A higher total chromatographic area was detected in the headspace of high IMF loins compared to low IMF ones. Several volatile compounds derived from lipid oxidative reactions, such as hexanol, octanal, (E,E)-2,4-heptadienal or (E)-2 decenal, and others from the degradation of certain amino acids, such as dimethylsulfide, 3-methylbutanal or phenylacetaldehyde, showed higher chromatographic areas in the headspace of high IMF loins than in low IMF ones. Thus, IMF content could influence both the generation of volatile compounds and the transfer of such compounds from the product matrix to the headspace. PMID- 22062611 TI - Distributions of brine and bacteria in beef primal cuts injected with brine without, or before or after mechanical tenderizing. AB - Eye of round primal cuts of beef were injected with brines containing a dye and Listeria innocua. The amounts of brine in portions of meat were determined from the concentrations of dye in the tissues, and the numbers of L. innocua in the tissues were determined from the numbers of colonies recovered on hydrophobic grid membrane filters incubated on a selective agar. Portions of meat from primals injected with brine after extensive mechanical tenderizing yielded L. innocua at numbers that would be expected from the amounts of brine in the meat. However, portions of meat from primals injected with brine without or before mechanical tenderizing yielded only about 10% of the expected numbers of L. innocua. The numbers of L. innocua recovered from injected meat that was not tenderized, relative to the amount of brine retained by the meat, declined with decreasing brine pressure and increasing strokes per minute of the needle head. When brine was injected at about 5% with low brine pressure and high head speed, the numbers of L. innocua retained in the meat were <1% of the expected numbers. When injected meat was examined microscopically, L. innocua were observed only between the muscle fibres in meat that was not tenderized before injection, but between fibres and in lacunae in tissue damaged by mechanical tenderizing before injection. The distributions of brine and bacteria in injected primals apparently did not alter substantially during storage in vacuum packs, at 2 degrees C, for 2 weeks. PMID- 22062612 TI - Effect of carrageenan level and packaging during ripening on processing and quality characteristics of low-fat fermented sausages produced with olive oil. AB - Eight low-fat fermented sausages were produced with partial replacement of pork backfat with olive oil. The total fat content of the sausages was 10% of which 8% was animal fat and 2% was olive oil. The sausages were produced with two types of carrageenan (iota- and kappa-) in four levels (0%, 1%, 2% and 3%). iota Carrageenan had a better effect (p<0.05) than kappa-carrageenan on such characteristics as pH, weight loss and lipid oxidation of the sausages, as well as, on sensory attributes. Low-fat fermented sausages with kappa-carrageenan had the same (p>0.05) firmness as high-fat commercial sausages (control). The carrageenan level of 3% negatively affected the firmness of the sausages. In a 2nd experiment, a high-fat control (30% total fat) and three low-fat fermented sausages (10% total fat) with olive oil were produced with three levels of iota carrageenan (0%, 1% and 2%). Low-fat sausages were vacuum packed for the last two weeks of ripening. iota-Carrageenan added at levels up to 2% had a positive effect (p<0.05) on the physicochemical and microbiological characteristics of the low-fat fermented sausages. The application of vacuum packaging over last two weeks of ripening improved the physicochemical and microbiological characteristics of the sausages and resulted in sensory attributes equal to or better than the high-fat controls. PMID- 22062613 TI - Discrimination of adult steers (oxen) and young cattle ground meat samples by near infrared reflectance spectroscopy (NIRS). AB - Near infrared reflectance spectroscopy (NIRS) was used to discriminate different types of ground beef samples. Fifty-three and sixty-seven samples of longissimus thoracis muscle corresponding to adult castrated steers (over 4 years old) and young cattle (under 14 months old), respectively, were homogenized and scanned over the NIR range (1100-2500nm). The results showed that NIRS could successfully discriminate 100% of ground beef samples depending on the sort of animal, probably as a consequence of differences in the intramuscular fat and water contents. Thus, NIRS is a fast, inexpensive, and non-destructive method that can be used to discriminate these beef products. PMID- 22062614 TI - The influence of storage and display conditions on the color stability of display ready pork loin roasts. AB - A total of 216 pork loin samples were utilized to examine the color stability of master-packed, display-ready pork cuts stored in three different atmospheres (100% CO(2), 100% N(2) and 70% O(2) and 30% CO(2)) at three storage temperatures (-1.5, 2, and 5 degrees C) for four day intervals up to 28 days, and then subsequently displayed aerobically for up to 30 hr. The composite results clearly indicated color stability was progressively lost during both chilled storage and subsequent aerobic display. However, retention of color stability was maximized by storage at -1.5 degrees C. In addition, storage in 100% CO(2) tended to maximize retention of color stability, despite the fact samples stored in 70% O(2) and 30% CO(2) were brighter and redder following storage and prior to subsequent aerobic display. PMID- 22062615 TI - The influence of storage and display conditions on the retail properties and case life of display-ready pork loin roasts. AB - A total of 216 pork loin subsections were utilized to investigate the effects of storage atmosphere (100% N(2); 100% CO(2); or 70% O(2) and 30% CO(2)), storage temperature (-1.5, 2 or 5 degrees C) and duration of chilled storage (<=28 days) and subsequent aerobic display (<=30 hr) on the retail properties and storage life of display-ready pork cuts. Composite results clearly emphasize the importance of subzero storage to the retail properties, and storage life of pork for all the types of storage atmosphere utilized. However, in the present study, controlled atmospheres of 70% O(2) and 30% CO(2) possessed the greatest preservative properties for masterpacked display-ready pork loin subsections (roasts) during chilled storage for up to 24 days, based upon visual and olfactory criteria. A decrease in retail appearance, attributable to a progressive increase in surface discoloration during both chilled storage and subsequent, aerobic display, resulted in a increase in the incidence of unacceptable packages, during both chilled storage and subsequent, aerobic display, which restricted chilled storage life to 20 days or less. Storage time consistently exerted the greatest influence on retail properties and generally accounted for 80% or more of the variation in most attributes evaluated. In addition, off-odors developed progressively during both chilled storage and subsequent, aerobic display, which further restricted chilled storage life to 12 days. Consequently, based upon previous cited results, for distribution of display-ready pork cuts to be successful, the hygienic quality of the commercial product must be improved. PMID- 22062616 TI - Chemical and structural changes in dry-cured hams (Bayonne hams) during processing and effects of the dehairing technique. AB - Pigs of similar genetic backgrounds and feeding regimes were slaughtered in two abattoirs, one carrying out dehairing by scalding and the other by singeing. One ham from each of 80 carcasses was retained. Sixteen fresh hams (8 from each dehairing technique) were used for analysis while 64 hams were processed into dry cured ham. Sixteen hams (8 from each dehairing technique) were taken for analysis at end of salting (day 14), end of rest (day 78), mid-processing (day 127) and end of processing (day 251). During processing, the water content of all muscles decreased while the salt content increased. The salt concentration in muscle water tended to equalize in all muscles. The nitrogen content of desalted dry matter (i.e. dry muscle tissue) decreased in both Biceps femoris and Semimembranosus. The content of every free amino acid increased with time, except for taurine and glutamine. Electrophoresis of the low ionic strength-soluble fractions showed all protein bands decreased during processing. Electrophoresis of the myofibrillar fractions indicated changes in all bands except actin (42kDa). These changes were more marked in the Semimembranosus than the Biceps femoris in the earlier processing steps. Ultrastructural changes were more marked in Semimembranosus than Biceps femoris. Hardness and chewiness increased in both muscles during the first half of processing then returned to values close to the initial ones in Semimembranosus but changed little in Biceps femoris. The scalded hams lost more weight than the singed ones during processing. The salt content was higher in scalded hams. Water-soluble nitrogen and NPN were higher in singed hams at the end of processing. The scalded hams were saltier and pungent. They had more pronounced aromas of dry ham, rancidity and hazelnut, and less aroma of fresh meat. Their texture was drier and less mellow. PMID- 22062617 TI - The problem of taint in pork-II. The influence of skatole, androstenone and indole, Presented individually and in combination in a model lipid base, on odour perception. AB - Responses to varying concentrations of androstenone and skatole in a neutral lipid base were studied using a trained 10-member panel. Concentrations for skatole and androstenone ranged between 0-1.32 and 0-6.0 MUg g(-1), respectively. Odour, androstenone and skatole intensities were assessed by the line scaling method. Triangular tests showed that the panel significantly distinguished indole from androstenone, p <= 0.01, but not from skatole nor mixtures of androstenone and skatole. Regression analyses showed linear relationships between skatole and androstenone concentrations and odour intensity but with a significant (p <= 0.01) androstenone-assessor interaction. Correlation coefficients with odour intensity were 0.64 and 0.63 for androstenone and skatole concentrations, respectively. Response surface curves showed that odour intensity depended on the linear terms of skatole, androstenone and on the quadratic term of androstenone. Androstenone and skatole intensity ratings revealed that the effect of skatole was enhanced by the presence of androstenone, but not the reverse. It was concluded that whilst both androstenone and skatole may be important for the sorting (classification) of pork, the importance of androstenone lies in its detection threshold whilst for skatole, the acceptability threshold may be a suitable criterion for quality control purposes. PMID- 22062618 TI - The problem of taint in pork-III. Odour profile of pork fat and the interrelationships between androstenone, skatole and indole concentrations. AB - Samples from 100 Large White * Meishan crossbred pigs (50 males, 50 females) with androstenone, skatole and indole concentrations ranging between 0-2.68, 0.004 1.43 and 0.007-1.57 MUg g(-1), respectively, were assessed by a trained 10-member sensory panel. The intensities of pork odour, abnormal odour, androstenone, skatole and odour pleasantness were assessed using line scaling. The descriptors mothball and musty associated with skatole and sweaty, dirty, silage and parsnips associated with androstenone all significantly (p < 0.05) characterised taint in pork. Regression analyses showed that pork odour depended on the linear terms of androstenone and indole, whilst abnormal odour depended on the linear terms of androstenone, skatole, indole and the quadratic terms of skatole and indole (r(2) = 0.76). Responses to different combinations of androstenone and skatole were sometimes similar. This implies that instrumentation for on-line sorting (classification) of pigs should be based on a response criterion instead of on concentrations. The equations derived in this study could be tested to form the basis for a reliable calibration system. PMID- 22062619 TI - Responses of two genotypes of chicken to the diets and stocking densities of conventional UK and Label Rouge production systems-II. Sensory attributes. AB - French Label Rouge quality chickens are reputed to possess improved sensory characteristics compared with birds reared under intensive conditions. The effects of genotype, diet, stocking density and age on eating quality were evaluated in a 2 * 2 * 2 experiment. The results suggest that genotype, diet, age and, to a lesser extent, stocking density can influence eating quality. The most pronounced sensory differences between the two genotypes were in the appearance and texture of the cooked meat. In particular, scores for toughness were higher for breast meat from Ross than ISA birds, though the opposite effect was observed for the thigh meat. Diet and age also affected texture, with the breast meat from chickens on the Label Rouge diet, or from older birds, having lower scores for toughness. Effects on odour and flavour were generally small and subject to genotype * diet interactions. The odour and flavour intensity of breast meat increased with age, while the odour intensity of thigh meat was higher in birds reared at low stocking density. PMID- 22062620 TI - The effect of fat-enriched diets on the perirenal fat quality and sensory characteristics of meat from rabbits. AB - Two hundred and eighty four medium sized young rabbits were fed ad libitum with two fat-enriched experimental diets (V: vegetable fat, A: animal fat) and a control diet (C). Diet had a significant effect on the ultimate pH (pHu) of the Longissimus dorsi muscle and on the colour, weight and fatty acid composition of the perirenal fat. The carcasses from diet C had significantly less perirenal fat (14.2 g) compared to the carcasses from group A and V (24.4 and 23.0 g) using carcass weight and age of the animals as covariables. Supplementing the diet with animal fat produced perirenal fat which was richer in oleic acid (41%) than in groups V (20.9%) and C (27.9%). The P:S ratio was higher in group V (2.45) compared with groups A and C (0.53 and 0.42). Diet also affected the organoleptic quality of the loin meat. The meat from groups V and C was considered to have a more aniseed flavour than that from group A. In contrast the loin meat from group A had more liver flavour. Both groups V and A were considered juicier than group C. No differences were found in hardness, chewiness and fibrousness. These results suggest than from a human health point of view, the use of a diet supplemented with animal fat is useful on the basis of the nutritional index, P:S of the perirenal fat. However the amount of fat added in the diets V and A should be less than used in this study if the carcass is sold whole in order to avoid excessive perirenal fat. From an organoleptic point of view, the greater aniseed and grass flavour of group V compared to group A may give meat of better sensory quality. PMID- 22062621 TI - Heating rate effects on high-fat and low-fat frankfurters with a high content of added water. AB - A study was made of the effect of heating rate (0.55, 1.10 and 1.90 degrees C min(-1)) on binding properties (cooking and purge losses) and texture (compression test) of high-fat (23%) and low-fat (9%) high added-water (19.8%) frankfurters during chilled storage (2 degrees C). Low-fat samples exhibited poorer (p < 0.05) binding properties; they were less hard and chewy (p < 0.05) but more cohesive and springy (p < 0.05) than high-fat frankfurters. Heating rate had little effect on binding properties. Hardness, cohesiveness, springiness and chewiness were greater (p < 0.05) at the slowest heating rate than at the other rates, behaviour being similar at the two higher rates. PMID- 22062622 TI - Composition analysis of beef rib sections by dual-energy X-ray absorptiometry. AB - Dual-energy X-ray absorptiometry (DXA) was used as a non-invasive method to measure composition of 9, 10,11 - rib sections obtained from 80 beef carcasses. The weights of the rib sections ranged from 2986 g to 6394 g. Each rib section was scanned twice by DXA, once in a horizontal or standing rib position (DXA-1) and once in a vertical position (DXA-2). After scanning, each rib section was dissected into fat, muscle and bone. The intramuscular fat content of the longissimus muscle was measured chemically. Dissected lean and fat values were adjusted for the amount of intramuscular fat. DXA lean values were adjusted for amount of bone (less bone mineral content). Both DXA measurements consistently overestimated the amount of fat relative to dissection. The DXA-1 scan position measured more lean and less fat than did DXA-2. The correlation (r) between the amount of dissected lean and DXA-1 and DXA-2 lean was 0.91 and 0.85, respectively and between the amount of dissected fat and DXA-1 and DXA-2 fat was 0.94 and 0.92, respectively. The high correlations between DXA and dissection results indicate that DXA could be used as a non-destructive method for evaluating composition of cuts of beef; however, attention must be given to orientation of the cut during the DXA scan. PMID- 22062623 TI - The design of pig stunning tong electrodes-A review. AB - The effectiveness of current electrical stunning systems for pigs is discussed and the need for improvements in the design and construction of stunning tongs and electrodes are explored. A review of existing stunning tong electrodes for use with free standing or restrained pig is discussed. The potential problems with existing systems are highlighted as: (1) the profile of the pigs head precludes the application of existing electrodes in the correct position; (2) the small area of contact enhances carbon build-up which increases electrical impedance; (3) the electrodes are easily tarnished with few cleaning tools provided. Good tong positions that span the brain are described as between the eye and ear on each side of the head, below the ear on each side of the head or, diagonal application between the top and bottom of the head. The notional contact impedance is the major component of resistance to current flow within the stunning system. The proposed use of different electrode designs and constructional material is investigated. The effect of the introduction of the fail-safe device would be to heighten the interest in contact impedance within the plant and that could ensure that the investigation of different electrodes is explored at least at plant level. PMID- 22062624 TI - Post-mortem calpain-system kinetics in lamb: Effects of clenbuterol and preslaughter exercise. AB - The effect of dietary supplementation with clenbuterol for either 8 days or 55 days in lambs was studied. The 55-day treatment was combined with an immediate preslaughter exercise regime. The effect of these treatments on post-mortem calpain system activities, meat ageing and meat quality was studied. Neither short-nor long-term supplementation had an effect on the rate of pH fall post mortem. Short-term supplementation had no effect on the initial nor the final shear force values but these were higher at intermediate times. In contrast, prolonged supplementation increased shear force values at all times post mortem. Preslaughter exercise, while influencing the rate of pH decrease in both control and supplemented groups, did not affect meat tenderness. After short-term clenbuterol-supplementation, the in-vitro MU-calpain activity was significantly lower in the supplemented group at 6 and 24 hr post mortem, while m-calpain and calpastatin activities were largely unaffected. In contrast, 55-day clenbuterol supplementation resulted in significantly higher levels of calpastatin activity at all times post mortem. These data imply that clenbuterol results in toughened meat due to alterations in the calpain/calpastatin system, the mechanisms of which are dependent upon the duration of supplementation. PMID- 22062625 TI - Effects of modified atmosphere storage on colour and microbiological shelf life of normal and pale, soft and exudative pork. AB - Pale, soft and exudative (PSE) and normal pork loins (n = 9 of each) were deboned, divided and packaged in modified atmospheres (MA) of 100% carbon dioxide containing 0, 0.5 and 1.0% residual oxygen (O(2)). The meat was stored at 3 degrees C, first in MA for 21 days, followed by 5 additional days under retail display conditions with access to air. Before packaging, PSE loins were more light and less red than those of normal meat. The drip loss after MA storage was twice as high from PSE meat as from normal meat. PSE meat was not more discoloured after MA storage than normal meat. The level of residual O(2) in the MA had a significant impact on the colour of the two types of meat. Discoloration was observed on both PSE and normal meat with 0.5% O(2) and even more clearly with 1.0% O(2), as demonstrated by instrumental and visual colour analyses. After MA storage, the microbiological shelf life and flora were not affected by the type of meat, or level of residual O(2). PMID- 22062626 TI - Thermal gelation of chicken, pork and hake (Merluccius merluccius, L) actomyosin. AB - Response surface methodology compared the effects of protein concentration (PC, 5 15 mg mL(-1)), ionic strength (NaCl concentration, IS, 0.1-0.7 M) and pH (5.2 7.5) on the gelation properties (penetration test) of natural actomyosin (NAM) from chicken, pork and hake muscle. Results indicated that, for Ln work of penetration (Ln WP), models had r(2) of 0.705 (p < 0.01) for NAM from pork, 0.813 (< 0.001) for NAM from chicken and 0.264 from hake (p > 0.05). The maximum work of penetration did not differ widely among the three samples, regardless of the fact that pH, NaCl level and protein concentration were different in each case. It was found that hake NAM only formed gels within a very narrow range of PC, pH and IS compared with chicken and pork NAM. In the latter two, maximum WP levels were found in gels formed within a pH range of 5.5-6.0 and ionic strength of 0.1 0.2 (NaCl, M). This suggests that hake protein is more sensitive to changes in environmental factors than that from pork or chicken. PMID- 22062627 TI - Comparative evaluation of some antioxidants in salame Milano and mortadella production. AB - Six formulations of salame Milano and mortadella were produced, one without antioxidants, two with sodium ascorbate (0.05-0.1 and O.2%), one with catechin, one with phytic acid, and one with sesamol. The products were studied for oxidation levels (peroxide value, TBARS, cholesterol oxides) and colour stability. The evaluation of the latter took place in conditions simulating commercial types of packaging (vacuum and modified atmosphere) and display. A significant difference emerged in colour stability. With the exception of salame Milano packed under modified atmosphere, in all cases salame and mortadella produced without Na ascorbate had significantly lower colour stability. Both in salame and mortadella, peroxide values and TBARS determination gave indications of a possible pro-oxidant effect of ascorbate 0.2% compared with an effective antioxidant activity of the other compounds tested. Cholesterol oxidation in salame appeared to be inhibited by sesamol and ascorbate while catechin was much less effective. In mortadella the prooxidant effect of Na ascorbate was confirmed. All lipid oxidation parameters, though, showed low oxidation values so that no quality nor health deficiencies could be envisaged with any of the formulations adopted. Lower colour stability scores, though, would create commercial problems. PMID- 22062628 TI - Overexpression of autophagy-related beclin-1 in advanced malignant melanoma and its low expression in melanoma-in-situ. PMID- 22062629 TI - Manganese superoxide dismutase inhibits neointima formation through attenuation of migration and proliferation of vascular smooth muscle cells. AB - Superoxide anion is elevated during neointima development and is essential for neointimal vascular smooth muscle cell (VSMC) proliferation. However, little is known about the role of manganese superoxide dismutase (MnSOD, SOD2) in the neointima formation following vascular injury. SOD2 in the mitochondria plays an important role in cellular defense against oxidative damage. Because of its subcellular localization, SOD2 is considered the first line of defense against oxidative stress and plays a central role in metabolizing superoxide. Because mitochondria are the most important sources of superoxide anion, we speculated that SOD2 may have therapeutic benefits in preventing vascular remodeling. In this study, we used a rat carotid artery balloon-injury model and an adenoviral gene delivery approach to test the hypothesis that SOD2 suppresses vascular lesion formation. SOD2 was activated along with the progression of neointima formation in balloon-injured rat carotid arteries. Depletion of SOD2 by RNA interference markedly promoted the lesion formation, whereas SOD2 overexpression suppressed the injury-induced neointima formation via attenuation of migration and proliferation of VSMCs. SOD2 exerts its inhibitory effect on VSMC migration induced by angiotensin II by scavenging superoxide anion and suppressing the phosphorylation of Akt. Our data indicate that SOD2 is a negative modulator of vascular lesion formation after injury. Therefore, SOD2 augmentation may be a promising therapeutic strategy for the prevention of lesion formation in proliferative vascular diseases such as restenosis. PMID- 22062630 TI - The C-terminal proteolytic processing of extracellular superoxide dismutase is redox regulated. AB - The antioxidant protein extracellular superoxide dismutase (EC-SOD) encompasses a C-terminal region that mediates interactions with a number of ligands in the extracellular matrix (ECM). This ECM-binding region can be removed by limited proteolysis before secretion, thus supporting the formation of EC-SOD tetramers with variable binding capacity. The ECM-binding region contains a cysteine residue (Cys219) that is known to be involved in an intersubunit disulfide bridge. We have determined the redox potential of this disulfide bridge and show that both EC-SOD dimers and EC-SOD monomers are present within the intracellular space. The proteolytic processing of the ECM-binding region in vitro was modulated by the redox status of Cys219, allowing cleavage under reducing conditions only. When wild-type EC-SOD or the monomeric variant Cys219Ser was expressed in mammalian cells proteolysis did not occur. However, when cells were exposed to oxidative stress conditions, proteolytic processing was observed for wild-type EC-SOD but not for the Cys219Ser variant. Although the cellular response to oxidative stress is complex, our data suggest that proteolytic removal of the ECM-binding region is regulated by the intracellular generation of an EC-SOD monomer and that Cys219 plays an important role as a redox switch allowing the cellular machinery to secrete cleaved EC-SOD. PMID- 22062631 TI - Frequency distribution of PRNP polymorphisms in the Pakistani population. AB - Prion diseases are neurodegenerative conditions caused by misfolding of a normal host-encoded prion protein (PrPC) into pathogenic scrapie prion protein (PrPSc). In human prion diseases, the M129V prion protein polymorphism is known to confer susceptibility to the disease, determines PrPSc conformation and alters clinicopathological phenotypes. To date, all clinicopathologically confirmed cases of a variant form of Cruetzfeldt-Jacob disease (vCJD) have been 129MM homozygotes. There is also predominance of 129MM homozygotes in sporadic CJD (sCJD). No information regarding prion disorders is available from Pakistan. Although only invasive procedures like brain biopsy can confirm the diagnosis of prion disorders, testing a corresponding human population for variation in the prion protein gene (PRNP) may provide some insights into the presence of these disorders in a locality. The current study therefore aimed at exploring the genetic susceptibility of Pakistani population to CJD. A total of 909 unrelated individuals including 221 hemophiliacs representing all 4 major provinces of Pakistan were screened for M129V polymorphism and insertions or deletions of octapeptide repeats (OPRIs/OPRDs) using Polymerase Chain Reaction coupled with Restriction Fragment Length Polymorphism (PCR-RFLP). Concordance of the results of some PCR-RFLP reactions was also confirmed by dideoxy automated Sanger sequencing. The frequencies of M129V alleles (129M and 129V) and genotypes (129MM, 129MV and 129VV) were found in all 909 individuals to be 0.7101, 0.2899, 0.5270, 0.3663 and 0.1067, respectively. Deletion of 1 octapeptide repeat (1 OPRD) was detected in heterozygous state in PRNP of 10 individuals and in homozygous state in 1 individual. An insertion of 3 octapeptide repeats (3-OPRI) was found in 1 individual and an insertion of 1 octapeptide repeat (1-OPRI) in two individuals. Both 3-OPRI and 1-OPRI were present in heterozygous state and were linked to 129M allele. There were no significant chi2 differences between M129V allelic and genotypic frequencies of healthy individuals and hemophiliacs. However, M129V allelic and genotypic frequencies differed significantly between Pakistani population and East Asian and Western populations. Non-significant chi2 differences between M129V frequencies of healthy individuals and hemophiliacs suggest that individuals manifesting single gene disorders may provide naturally randomized samples for studies aiming at surveying the genetic variation. The combined excess of 129MM and 129VV homozygosity and the presence of 3-OPRI in 1 individual imply that Pakistani population is susceptible to prion disorders. Cases of prion disorders may exist in Pakistan, albeit at lower annual prevalence than other countries where life expectancy is greater than 65 years. PMID- 22062632 TI - Contribution of SNP arrays in diagnosis of deletion 2p11.2-p12. AB - Deletions of the short arm of chromosome 2 are exceedingly rare, having been reported in few patients. Furthermore most cases with deletion in 2p11.2-p12 have been studied using standard karyotype and so it is not possible to delineate the precise size of deletions. Here, we describe a 9-year-old girl with a 9.4 Mb de novo interstitial deletion of region 2p11.2-p12 identified by SNP array analysis. The deleted region encompasses over 40 known genes, including LRRTM1, CTNNA2 and REEP1, haploinsufficiency of which could explain some clinical features of this patient such as mental retardation, speech delay and gait abnormalities. A comparison of our case with previously reported patients who present deletions in 2p11.2-p12 was carried out. Our case adds new information to the deletion of 2p11.2-p12, improving the knowledge on this rearrangement. PMID- 22062633 TI - Interrelationships amongst carcass and meat quality characteristics of sheep. AB - The relationships between various carcass and meat quality characteristics of sheep were studied. Relationships were determined by regression, using data obtained from sheep belonging to a wide range of breeds, sex types and slaughter weight (32-62 kg). The chilling rate of the M. longissimus dorsi (LD) post-mortem was negatively correlated with carcass weight (r=-0.42, P<0.01), back fat thickness (r=-0.54, P<0.001) and the cooking loss of the M. infraspinatus (IS) muscle (r=-0.44, P<0.001). Correlation between chilling rate and shear force of the IS muscle was not significant, which was also the case between chilling rate and the cooking loss and shear force of the LD and M. triceps brachii muscles. A positive relationship was observed between total collagen and cooking loss (r=0.34, P<0.05) and between heat-insoluble collagen and cooking loss of the LD muscle (r=0.37, P<0.01). Generally collagen content was positively correlated with lean content and negatively with fat content. Carcass weight was significantly (P<0.001) correlated with intramuscular fat (r=0.61), moisture (r= 0.76), cooking loss (r=-0.49), shear force (r=-0.41) and hue angle (r=-0.41). Shear force was positively associated with cooking loss (r=0.42, P<0.001), but negatively with intramuscular fat content (r=-0.55, P<0.001). Cooking loss was positively correlated with moisture content (r=0.55, P<0.001). PMID- 22062634 TI - Salt distribution in dry-cured ham measured by computed tomography and image analysis. AB - Forty-seven hams were scanned four times by computed tomography (CT) while being manufactured into dry-cured hams. An image-processing algorithm measured CT values in the lean part of the hams and provided line profiles reflecting the magnitude and spatial location of salt gradients. At the end of manufacturing, seven entire hams were dissected and the salt content of the lean part determined. Likewise, in the remaining 40 hams, the lean meat of the slices corresponding to the CT images was dissected, analyzed chemically for NaCl and compared to the CT value. The salt content of entire dry-cured hams correlated well (r(2)=0.94) to the CT value of a 10 mm section located at the center of femur bone, perpendicular to the length axis of the hams. In the same position, significant correlations between the CT values before (r(2)=0.71) and after (r(2)=0.80) the ageing period and actual chemical analysis of the same section were demonstrated. Line profiles illustrating the combined salt distribution and dehydration within a ham related to the physical characteristics of the ham as well as to the manufacturing process. These findings reveal that the effects of altered manufacturing practices can be followed non-invasively, while hams are still in production. Computed tomography combined with appropriate image analysis offers advantages as a non-invasive tool in both research and product development. PMID- 22062635 TI - The relationship between slow and fast myosin heavy chain content, calpastatin and meat tenderness in different ovine skeletal muscles. AB - The present study investigated the relationship between fibre type distribution and slow (MHC-s) and fast (MHC-f) myosin heavy chain content on calpastatin and meat tenderness in longissimus dorsi (LD), tensor fasciae latae (TFL), semitendinosus (ST), trapezius (TZ) and supraspinatus (SS) muscles from six Mule*Charolais rams. Samples taken at slaughter were frozen either in liquid N(2) for analysis of MHC-s and MHC-f by immunoblotting, or in cooled isopentane for histochemical fibre typing. Calpastatin activity and an immunoreactive 135 kDa calpastatin band were analysed in samples taken 24 h postmortem. Shear force was determined on muscle chops taken at 24 h postmortem and conditioned until day 14. The intensity of MHC-s and MHC-f immunopositive bands correlated with %Type I and %Type II fibres identified histochemically (r(2)=0.612 and 0.366, respectively, p<0.001). Muscle specific differences were observed in MHC-s and MHC-f immunoreactivity, fibre type distribution, calpastatin activity, calpastatin 135 kDa immunoreactivity and shear force. MHC-s correlated positively with calpastatin activity (r(2)=0.725, p<0.001) and 135 kDa calpastatin (r(2)=0.228, p<0.01) across all muscle types. The data show that detection of MHC-s can be used to identify fibre type differences between ovine muscles and that this correlates with differences in calpastatin content and inhibitory activity, but not tenderness. PMID- 22062636 TI - Influence of different gas compositions on the short-term storage stability of mother-packaged retail-ready lamb packs. AB - Longissmus dorsi muscles were removed from Suffolk cross-breed lambs (aged 4-9 months) and cut into steaks. Lamb steaks were over-wrapped on trays and placed in vacuum pack bags. Bags were divided into 3 groups and flushed with gas mixtures containing 100:0, 90:10 or 80:20/CO(2):N(2). Mother packed lamb bags were stored for 4 days (T2) and 7 days (T3), respectively, in darkness at 4 degrees C, prior to retail display. The effect of aerobic packaging alone on lamb meat quality was used as the control (T1). Under retail display, all over-wrapped trays were held under refrigerated conditions (4 degrees C, 616 lx) for up to 8 days. Steaks were assessed for microbial growth, oxidative and colour stability as well as pH every 2 days. Mother-packing in 100:0/CO(2):N(2) was the most effective way of extending the storage life of retail ready lamb prior to display, particularly over longer storage periods. TVCs for T3 lamb meat using all gas compositions remained below 2.0*10(6) CFUs/g meat up until day 6 compared to day 4 in both T1 and T2 lamb. Lipid oxidation in lamb mother-packed for 7 days occurred at a faster comparative rate than discolouration and microbial growth and was the major determinant of shelf-life. However, under simulated retail display in aerobic packages, TBARS values did not increase significantly. There was no significant difference between Hunter 'a' values for T3 lamb meat and the control, but T3 meat mother-packed in 100:0/CO(2):N(2) had higher 'a' values than those of the control and T3 meat packed in other gas compositions. Lamb steaks in T3 previously mother-packed in 100:0/CO(2):N(2) were also significantly (p<0.05) higher than those of T2 on day 0. T3 meat also maintained initial colour values over those of the control. PMID- 22062637 TI - Autofluorescence quantifies collagen in sausage batters with a large variation in myoglobin content. AB - In order to clarify the potential of the method of autofluorescence for determining the collagen content in meat batter, an experimental design was used where the emission originating from collagen was unrelated to the effect of myoglobin absorbance on the emission spectra. Muscles like beef Masseter, beef Latissimus dorsi and pork Glutens medius assured a large variation in myoglobin content, and made absorbance from myoglobin account for 65-84% of the variation in the emission spectra at wavelengths normally thought interesting for collagen quantification. Collagen (range 1.3-4.0%) accounted for 7-18% of the variation in the autofluorescence emission spectra. Collagen content could be predicted from the emission spectra provided multivariate regression techniques were used. Pre processing of spectra reduced the prediction error for collagen by 0.03-0.12%, depending on method used; the lowest prediction error obtained being 0.48%. The method of autofluorescence gave lower prediction errors for collagen content than did the method of near infrared reflectance when applied to the same batters. PMID- 22062638 TI - Analysis of raw meats and fats of pigs using polymerase chain reaction for Halal authentication. AB - A method for species identification from pork and lard samples using polymerase chain reaction (PCR) analysis of a conserved region in the mitochondrial (mt) cytochrome b (cyt b) gene has been developed. Genomic DNA of pork and lard were extracted using Qiagen DNeasy((r)) Tissue Kits and subjected to PCR amplification targeting the mt cyt b gene. The genomic DNA from lard was found to be of good quality and produced clear PCR products on the amplification of the mt cyt b gene of approximately 360 base pairs. To distinguish between species, the amplified PCR products were cut with restriction enzyme BsaJI resulting in porcine-specific restriction fragment length polymorphisms (RFLP). The cyt b PCR-RFLP species identification assay yielded excellent results for identification of pig species. It is a potentially reliable technique for detection of pig meat and fat from other animals for Halal authentication. PMID- 22062639 TI - Reducing the sodium content in meat products: The effect of the formulation in low-sodium ground meat patties. AB - This study investigated the effect of formulation on quality characteristics of low-sodium ground meat patties. The variation in sodium content was achieved by varying the NaCl content. The formulation variables studied were sodium and fat content and the use of phosphate. The patties were made using 50% or 60% meat in the formulations. Formulation affected the perceived saltiness of ground meat patties. Fat and lean meat content affected perceived saltiness, but their effects were opposite. When the fat content was increased the perceived saltiness increased, but when the meat content increased the perceived saltiness decreased. However, the effect of fat content on perceived saltiness was less than the effect of meat content. The use of phosphate effectively decreased cooking loss, particularly of high-fat-low-sodium patties. The same firmness could be reached with lower sodium content when phosphate was used. PMID- 22062640 TI - Consumer choice and suggested price for pork as influenced by its appearance, taste and information concerning country of origin and organic pig production. AB - Reactions of consumers to the appearance and taste of pork with and without information concerning outdoor production of pigs were tested in France, Denmark, Sweden and UK. Consumers in all four countries focussed on colour and fatness rather than marbling and drip to make their choice. Almost half of the British and Danish preferred the paler and the French the darker pork. Most people preferred the leaner pork. When information was provided in the form of labels, the vast majority of consumers preferred the pork labelled as originating from their own country as opposed to 'imported' and that labelled as pork from pigs 'raised outside' as opposed to 'inside'. There was no difference in the taste of grilled pork from indoor and outdoor production systems but pork labelled 'home produced' or 'outdoor' were more appreciated. Consumers' willingness to pay varied widely and was higher for those consumers who found more of the characteristics they sought. Consumers offered about 5% more for 'home country' and 'raised outside' labels. PMID- 22062641 TI - Effect of carbon dioxide on autoxidation and photooxidation of nitrosylmyoglobin. AB - Autoxidation and photooxidation of nitrosylmyoglobin, MbFe(II)NO, the pigment of nitrite-cured meat, was investigated in aqueous solution saturated with gas mixtures containing varying levels of CO(2) (0%, 20% and 90%) in the presence of either 1.5 or 10% O(2) and balanced with N(2) in order to mimic modified atmosphere (MA) packaging of meat products. Quantum yields for photooxidation at 1.5% O(2) for monochromatic UV-light (366 nm) were slightly higher than for visible light (436 nm) in agreement with previous findings, while the quantum yields showed no dependence on the CO(2) levels. Autoxidation of MbFe(II)NO was evaluated by global analysis of spectral data applying a kinetic model with two consecutive reaction steps, and the second rate constant was significantly reduced at the highest CO(2) level investigated, while the rate constant of the initial reaction step was found independent of the CO(2) levels. The varying dependence observed for autoxidation and photooxidation of MbFe(II)NO in relation to CO(2) level confirms the differing reaction mechanisms for the two types of MbFe(II)NO degradation. Photooxidation of nitrite-cured meat products packed in MA is accordingly expected to be independent of the presence of varying CO(2) levels, while thermal oxidation (autoxidation) of MbFe(II)NO is reduced at elevated levels of CO(2), which may be of some relevance during product storage and retail display. PMID- 22062642 TI - Assessment of postmortem proteolysis by gel-based proteome analysis and its relationship to meat quality traits in pig longissimus. AB - This study was conducted to assess postmortem proteolysis using a proteomics approach, and to determine the relationship of proteolysis to WB-shear force, drip loss, and hunter L(*) value during chiller ageing in pig longissimus muscle. To generate various meat qualities, 20 male landraces were assigned into 2*2 factorial (10 pigs fasted for 18 h and 10 pigs fed until the morning of slaughter*20 sides placed at -3 degrees C and 20 sides at 6 degrees C). An interaction between muscle temperature at pH 6.2 (TpH6.2) and ageing for both WB shear force and drip loss showed that a high TpH6.2 produced meat with a lower shear force, but the advantage was gradually eroded by extended ageing (i.e., 1, 3 and 7 d). On the other hand, the detrimental effect of a high TpH6.2 on drip loss became more apparent as ageing time increased (i.e., 3 and 7 d). Changes in the objective quality traits and semi-quantitative spot density for 27 out of 133 identified proteins coincided during ageing. The proteins included myosin light chain 1, desmin, troponin T, cofilin 2, F-actin capping protein beta subunit, ATP synthase, carbonate dehydratase, triosephosphate isomerase, actin and its relevant peptides, peroxiredoxin 2, alpha-b crystalline and heat shock protein 27 kDa. PMID- 22062643 TI - Occurrence of conjugated linoleic acid in longissimus dorsi muscle of water buffalo (Bubalus bubalis) and zebu-type cattle raised under savannah conditions. AB - Lipid extracts from longissimus dorsi muscles of 64 water buffaloes and 68 zebu type cattle were used to quantify the amount (mg/g of lipids) of total conjugated linoleic acid (CLA), CLA isomers c9, t11 and t10, c12 and linoleic acid (LA), according to species (buffaloes and cattle), age (slaughter groups at 7, 17, 19 or 24 months of age) and gender (bulls and steers). The effects of gender and age were significant (P<0.05) but marginal. Comparisons of lipid extracts from buffaloes vs. cattle showed that total CLA (1.83 vs. 1.47 mg/g), CLA c9, t11 (1.27 vs. 1.01 mg/g) and CLA t10, c12 (0.56 vs. 0.47 mg/g) isomers as well as the CLA/LA ratio (0.10 vs. 0.07) were higher (P<0.05) in buffalo lipids. Considering the sparingly low lipid concentrations (<2 g/100 g of fresh muscle) none of the meat species should be considered a significant source of CLA. PMID- 22062644 TI - The mineral composition and microscopic changes in thoracic buttons of Chinese Yellow steer with age. AB - Tips of sacral, lumbar and thoracic vertebrae were sampled from 67 Chinese Yellow steer carcasses to determine relationships of the mineral composition in tips of vertebrae to the ossification degree as well as the dental age. Thoracic buttons were taken from another 11 Chinese Yellow steer carcasses to study their microscopic changes with age. Percentages of ash, calcium and phosphorus in thoracic buttons, on a fresh weight basis, increased with increasing ossification degree (R(2)=0.9815, 0.9743, 0.9817, respectively) and dental age (R(2)=0.9496, 0.9455, 0.9209, respectively), but those in tips of lumbar and sacral vertebrae varied little (P>0.05). Based on the same levels of ash percent in thoracic buttons, a corresponding relationship between the ossification degree and the dental age was observed: thoracic buttons did not ossify when the dental age was under 24 months; and 10%, 30%, and 40% of thoracic buttons ossified at the dentition-based age of 36, 50, and 60 months. Observations by scanning electron microscopy indicated that cartilages of Chinese Yellow steer thoracic buttons began to ossify at approximately 24 months and ossified completely at 84 months. The present study could be useful to improve the accuracy of age estimation for Chinese Yellow steers in the Chinese beef grading system. PMID- 22062645 TI - Influence of genetic type, live weight at slaughter and carcass fatness on fatty acid composition of subcutaneous adipose tissue of raw ham in the heavy pig. AB - The study aimed to assess some quality traits of the subcutaneous adipose tissue of raw ham for Parma production, obtained from 56 "traditional" Landrace*Large White (L*LW) and 56 Cotswold commercial hybrid (CH) pigs reared in the same conditions and slaughtered at an average live weight (l.w.) of about 165 kg. Further, the relationships between lipid composition, l.w. and carcass fatness were studied. Compared to the CH, the fatty tissue of L*LW pigs showed a lower water (6.33% vs. 7.35%, P<0.01) and a higher lipid (91.18% vs. 90.18%, P<0.01) content. CH lipids had higher polyunsaturated fatty acids (16.53% vs. 13.75%, P<0.01), and smaller saturated fatty acids (38.20% vs. 40.26%, P<0.01) content and a higher iodine value (69.69 vs. 65.22, P<0.01). An increased slaughter weight was associated with a lower degree of lipid unsaturation, but only the lowest weight class (<160 kg) showed a significant difference compared to the other two classes (?160<170 and ?170 kg). Regardless of genetic type or l.w. class, an increase in backfat thickness is associated with an increase in saturated and monounsaturated fatty acids and a remarkable reduction in polyunsaturated content. PMID- 22062646 TI - The use of Bayesian statistics in meat quality analyses: a review. AB - A Bayesian approach to meat quality analyses is discussed and compared with the classical statistical approach. Inferences from means, medians and modes of marginal posterior distributions are presented, and a variety of probability inferences and confidence intervals are presented and discussed. Classical and Bayesian theories of hypothesis testing are compared and their advantages and disadvantages are discussed. Fundamentals of Bayesian inference and Monte-Carlo Markov Chain (MCMC) techniques are presented and discussed. The great flexibility for inferences introduced by MCMC techniques is stressed. Practical examples of meat quality analyses are given, with references to available free software to analyze a large variety of models. PMID- 22062647 TI - A Bayesian approach to the effect of selection for growth rate on sensory meat quality of rabbit. AB - The effect of selection for growth rate on the sensory characteristics of rabbit meat was assessed by comparing a selected and a control population of rabbits. Embryos belonging to generation 7th were frozen, thawed and implanted in does in order to produce the control group. The control group was formed from the offspring of the embryos belonging to the 7th generation. Selected animals belonging to 21st generation (S) were compared with animals of the control group (C), both were contemporary. Forty animals per group were slaughtered at 9-weeks old. The sensory analysis was carried out on samples of the Longissimus dorsi muscle. The parameters evaluated were: intensity of rabbit flavour (IRF), aniseed odour (AO), aniseed flavour (AF), liver flavour (LF), tenderness (T), juiciness (J), fibrousness (F). A Bayesian analysis was performed. The ratio of the selection and control effects was analysed. There was a difference between the selected and control groups for IRF, AO, AF and LF. Conversely, no differences were found in T, J and F between groups. Selected group had 3% and 23% higher values of IRF and LF, respectively, than the control group. A relevant effect of selection on AO and AF appeared (probability of relevance P(r)=1), with lower values for selected animals. There was a difference between male and female groups for IRF, but this was not relevant. No differences between sexes were found for the rest of the characteristics evaluated. Selection for growth rate did not affect the main sensory characteristics of meat, like T and J but, it had a negative effect on some flavour characteristics. PMID- 22062648 TI - Study of the branched hydrocarbon fraction of intramuscular lipids from Iberian dry-cured ham. AB - Branched hydrocarbons from the unsaponifiable lipid fraction of intramuscular fat from Iberian dry-cured hams were analyzed. Thirty-four hams were distributed into four groups according to the feed system of the pigs (extensive system "Montanera" and intensive system "Pienso") and genotype (Iberian and Iberian*Duroc). A total of 35 different hydrocarbons were identified in this study. Some differences were found in the levels of branched, cyclical and unsaturated hydrocarbons as a function of the diet of the pigs (3-hexyl-1,1 dimethyl cyclopentane, p<0.05; 3-octadecene, p<0.01; neophytadiene, p<0.001; 1 ethylundecyl benzene, p<0.01; cyclohexadecane, p<0.001; cyclotriacontane, p<0.05). However, the genotype had a limited effect in the level of branched hydrocarbons found. The study of branched hydrocarbons in intramuscular fat from dry-cured Iberian ham allows differentiation between the pigs management systems. PMID- 22062649 TI - Effect of processing conditions on the quality of naturally fermented Turkish sausages (sucuks). AB - Effects of temperature and different fat levels on the quality of Turkish sausages (sucuks) were studied during the ripening period. Sausage batters prepared at 10%, 20% and 30% fat levels were processed at 20-22 and 24-26 degrees C. A high ripening temperature and low fat level caused fast dehydration. Fat level affected water activity, colour, total viable and lactic acid bacteria counts of the sausages. Increasing fat content and ripening temperature resulted in high lightness (L*) and yellowness (b*) and low redness (a*) at the end of ripening. The sausages with 10% fat resulted in higher redness values. Growth of total viable and micrococci-staphylococci bacteria was affected by ripening temperature. Sausages ripened at 24-26 degrees C had a rapid increase in micrococci-staphylococci counts. PMID- 22062650 TI - Activity of porcine muscle glycogen debranching enzyme in relation to pH and temperature. AB - The activity of glycogen debranching enzyme (GDE) was studied in relation to pH value and temperature in porcine masseter and longissimus dorsi muscles. A glycogen limit dextrin was used as the substrate for GDE, and the enzyme was derived from raw meat extracts. In both muscles, the pH only weakly affected the activity of GDE at the pH values found in carcasses post-slaughter. However, the activity of GDE decreased strongly (P<0.001) when the temperature decreased from values of 39 and 42 degrees C, found just after slaughter to values of 4 and 15 degrees C. In both muscles the activity of GDE began to fall at temperatures below 39 degrees C and was almost zero when the temperature decreased to below 15 degrees C. Thus, the activity of GDE may control the rate of glycogenolysis and glycolysis, but does not block rapid glycolysis and pH decrease when the temperature is high. This may be important in PSE meat, where the pH decreases rapidly at high temperatures, but rapid cooling could limit the activity of GDE and thus glycogenolysis. As expected, GDE was more active in the light longissimus dorsi muscle than in the dark masseter muscle. PMID- 22062651 TI - Effects of feeding in free-range conditions or in confinement with different dietary MUFA/PUFA ratios and alpha-tocopheryl acetate, on antioxidants accumulation and oxidative stability in Iberian pigs. AB - The experiment was undertaken to provide information of the influence of feeding either free-range or in confinement with different dietary MUFA/PUFA ratios and alpha-tocopheryl acetate supplementation (40 vs. 200 mg/kg) on tocopherol content and susceptibility to lipid oxidation of muscle and microsomes in Iberian pigs. The grass provided to the pigs had a similar alpha-tocopherol concentration to that observed for diets supplemented with 200 mg/kg alpha-tocopheryl acetate, and acorns supplied fourfold higher content of gamma-tocopherol than the experimental diets. The alpha- and gamma-tocopherol contents of muscle reflected the tocopherol concentration of the diets. Mono and Medium diets produced a similar MUFA/PUFA ratio in neutral and polar lipids of pig muscle to those fed outdoors. The lowest TBARS numbers were found in muscle samples from pigs fed a MUFA enriched diet in confinement. No significant influence of free-range feeding or dietary fat on drip loss was found. However, alpha-tocopheryl acetate supplementation reduced (P<0.05) drip loss. Dietary vitamin E supplementation decreased the membrane lipid oxidation by 18% after 120 min. However, free-range feeding decreased the extent of microsome oxidation by 20%, 56% and 82% after 120 min when compared with those groups fed in confinement with high, medium and low MUFA/PUFA ratios, respectively. The hexanal concentration of muscle showed a similar trend to that observed for microsome induced-oxidation, suggesting, that hexanal determination is a more accurate method to measure lipid oxidation in iberian pig muscle than the thiobarbituric acid test. PMID- 22062652 TI - Studies on time-related changes of dipeptidyl peptidase during processing of Jinhua ham using response surface methodology. AB - Sixty experimental Jinhua hams were processed by traditional methods using green hams from local cross-bred pigs of Lanxi, Zhejiang province, PR China. Biceps femoris was sampled from five hams randomly taken after each processing stage. Potential activities of DPP I and IV in addition to the changes of some enzyme influencing factors were determined. The effects of temperature, sodium chloride content, sodium nitrate content and pH value on the activities of muscle DPP I and IV were evaluated using Response Surface Methodology (RSM) and the actual activities of muscle DPP I and IV during Jinhua ham processing were estimated. The results showed that potential activity of muscle DPP I decreased gradually from 8608.23 to 1842.06 Ug(-1) before loft-aging and then increased gradually from 1842.06 to 12196.60 Ug(-1) at the end, while that of muscle DPP IV decreased continuously and about 11% of the initial potential activity was left at the end of processing. Most of the chemical components analyzed in Biceps femoris as well as physical parameters changed greatly during processing. Temperature, sodium chloride concentration and pH value influenced DPP I and IV activities significantly. However, nitrate concentration from 0 to 50 mgkg(-1) showed little effect. By regression analysis, two quadratic regression equation models were built. The models showed that DPP I could have strong activity during Jinhua ham processing, whereas the activity of DPP IV was always very weak despite its strong potential for activity. In conclusion, muscle DPP I may be a key enzyme responsible for the generation of dipeptides in Jinhua ham processing while the effect of DPP IV was possibly very limited. PMID- 22062653 TI - Effect of finishing mode (pasture- or mixed-diet) on lipid composition, colour stability and lipid oxidation in meat from Charolais cattle. AB - Effects of pasture- or mixed-diet finishing mode on colour and lipid stability were measured in meat from Charolais steers, heifers and cows of different ages after refrigerated storage. Meats from pasture- and mixed-diet finished cattle have more or less significant differences in lipid composition which will influence the colour and lipid stability. The mixed-diet finished cattle have about the same proportions of saturated and monounsaturated lipids as pasture diet finished animals; on the contrary, cattle fed on grass have higher proportions of n-3 PUFA, and to a less extent, of n-6. Finishing diet had an important effect on lipid stability, meat from pasture-finished animals showing significantly lower TBA-RS level than meat from mixed-diet finished animals. Effect of diet was also significant on myoglobin content with a higher content of haeminic iron in mixed-diet finished animals. Effect of diet on colour stability was slight with a beneficial effect of pasture finishing mode, significant only in heifers, and after a meat storage of six days in air. PMID- 22062654 TI - Absolute immunoquantification of the expression of ABC transporters P glycoprotein, breast cancer resistance protein and multidrug resistance associated protein 2 in human liver and duodenum. AB - The ATP-binding cassette (ABC) transporters breast cancer resistance protein (BCRP), multidrug resistance-associated protein 2 (MRP2), and P-glycoprotein (Pgp) are important in the distribution and elimination of many drugs and endogenous metabolites. Due to their membrane location and hydrophobicity it is difficult to generate purified protein standards to quantify these transporters in human tissues. The present study generated transporter proteins fused with the S-peptide of ribonuclease for use as standards in immunoquantification in human liver and small intestine. Quantification of the S*tagTM, a 15 amino acid peptide, is based on the formation of a functional ribonuclease activity upon its high affinity reconstitution with ribonuclease S-protein. S-tagged transporters were used as full-length protein standards in the immunoquantification of endogenous BCRP, MRP2, and Pgp levels in 14 duodenum and 13 liver human tissue samples. Expression levels in the duodenum were 305+/-248 (BCRP), 66+/-70 (MRP2), and 275+/-205 (Pgp) fmoles per cm(2). Hepatic levels were 2.6+/-0.9 (BCRP), 19.8+/-10.5 (MRP2), and 26.1+/-10.1 (total Pgp) pmoles per g of liver. The mean hepatic scaling factor was 35.8mg crude membrane per g of liver, and the mean duodenal scaling factor was 1.3mg crude membrane per cm(2) mucosal lining. Interindividual variability was greater in duodenal samples than liver samples. It is hoped that this innovative method of quantifying these transporters (and other membrane proteins) will improve in vivo-in vitro extrapolation and in silico prediction of drug absorption and elimination, thus supporting drug development. PMID- 22062655 TI - Effects of vitamin E supplementation on fattening performance, non-carcass components and retail cut percentages, and meat quality traits of Awassi lambs. AB - This experiment was carried out to evaluate the effects of vitamin E supplementation on growth, non-carcass components and retail cut percentages, and meat quality traits of Awassi male lambs at approximately 8 months of age. The lambs were divided into two groups as control (CG, n=12) and experimental (VG, n=12) at the beginning of the fattening period. The CG and VG lambs were fed with a concentrate and grass hay close to ad-libitum by biweekly adjustment of the amount offered. In addition, the VG received a supplement of 45 mg vitamin E per lamb per day during a 75-day fattening period. Inital weight, final weight, daily weight gain and feed conversion efficiency were 31.8+/-1.40 kg, 45.5+/-1.37 kg, 183+/-13 g and 7.6 for CG, 32.5+/-1.45 kg, 46.7+/-1.42 kg, 189+/-15 g and 7.0 for VG, respectively. Vitamin E supplementation did not have a statistically significant effect on animal performance traits, non-carcass components and retail cut percentages, but produced an 8.1% improvement in feed conversion efficiency. After slaughter, carcasses were chilled at 4 degrees C for 24 h. Then, the carcasses were dissected into wholesale cuts, and m. longissimus dorsi (LD) muscles excised. The samples of muscle were subjected to moisture, protein, ether extract and ash analyses. Samples were cooked for shear test and cooking yield measurements. There were no significant differences between CG and VG lamb groups in chemical composition of meat samples from the LD muscles. Though the influence of vitamin E supplementation on color parameters (L*, a*, b*) was not statistically significant, the mean a* (redness) values decreased on days 2 and 4 and increased on days 7 and 12 of the storage period. However, the a* values of muscles from the VG were higher than those grouping CG. L* and a* values in LD muscle from vitamin E-treated lamb groups were also preserved for a period of 12 days of maturation. In this study, drip loss was relatively preserved by vitamin E supplementation to the diet of animals. The results showed that vitamin E supplementation to the diet of Awassi male lambs at an inclusion rate over the amount of nutritional recommendations relatively reduced lipid oxidation, drip loss and tended to maintain meat redness. PMID- 22062656 TI - Lipolysis and lipid oxidation during chilled storage of meat from Large White and Pietrain pigs. AB - The day after slaughter, six chops of Longissimus lumborum from each of 10 Large White pigs and six Pietrain pigs were packed individually under vacuum and kept at 3-4 degrees C in the dark. At 1, 5 and 9 days after slaughter, two chops were used for analysis of lipids, thiobarbituric acid reactive substances (TBARS), sarcoplasmic Ca(2+) and sarcoplasm and mitochondria phospholipase A(2) activity. Free fatty acid content was higher in Pietrains than in Large Whites and increased with keeping time. Total lipids of Large White pigs contained more saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) and less polyunsaturated fatty acid (PUFA). Large Whites had less dioleoyl-linoleyl glycerol (OOL) and Palmitoyl-oleoyl-linoleyl-glycerol (POL) and more Palmitoyl oleoyl-stearyl-glycerol (POS) than Pietrains. The percentages of SFA and MUFA decreased and the percentage of PUFA increased with time in FFA of Large White pigs. In Pietrains, similar changes were observed between days 1 and 5, but later the percentages of SFA increased and the percentage of PUFA decreased again. TBARS tended to increase with time particularly in Pietrains. Sarcoplasmic phospholipase A(2) decreased between days 5 and 9 in both breeds. Sarcoplasmic calcium was markedly higher at day 1 in Pietrains than in Large Whites then the difference decreased. These breed differences in lipid composition differences and lipid changes during storage are considered too small to be of practical importance, for instance in influencing the choice of a breed for pork production. PMID- 22062657 TI - Functional properties of raw and cooked pork patties with added irradiated, freeze-dried green tea leaf extract powder during storage at 4 degrees C. AB - Functional and sensory properties of raw and cooked pork patties with added irradiated freeze-dried green tea leaf extract powder were studied. Components of green tea were extracted by 70% ethanol, and the extract was irradiated to obtain a bright color. The irradiated green tea extract was freeze-dried and the powdered sample (0.1%) was added to the pork patties (Trt C). Pork patties without any ingredient (Trt A) and with nonirradiated, freeze-dried green tea extract powder (Trt B) were also prepared for comparison. Lipid oxidation, radical scavenging effect, color, and sensory properties of pork patties with treatments were analyzed at 5-day intervals for 15 days with storage at 4 degrees C. The lipid oxidation had a lower (P<0.05) and radical scavenging effect was greater (P<0.05) in the raw and cooked pork patties with added Trt B and Trt C, than those of Trt A (control). The pork patties with Trt B and Trt C had a higher Hunter color a*-value and less cooking loss than that of Trt A. Sensory panelists preferred the odor of the raw pork patties and color of the cooked pork patties of Trt C (P<0.05). Generally, no significant difference between Trt B and Trt C was found. Therefore, irradiated, freeze-dried green tea extract powder can be used for producing functionally-improved meat products. PMID- 22062658 TI - Lipid oxidation of pressurized and cooked chicken: role of sodium chloride and mechanical processing on TBARS and hexanal values. AB - Lipid oxidation of pressurized (300 and 500 MPa for 30 min at 20 degrees C) or cooked (90 degrees C for 15 min) minced chicken breast and slurries was evaluated. Mechanical processing, before and after pressurization and cooking, and addition of sodium chloride were also tested as prooxidant factors. At 1, 3, 6 and 9 days of storage at 4 degrees C, thiobarbituric acid reactive substances (TBARS) and hexanal were quantified by means of the TBARS test and solid phase microextraction, respectively. In general, pressurized samples presented less oxidation compounds than cooked samples. Thiobarbituric acid reactive substances and hexanal values tended to rise with increasing storage time. Both parameters showed similar patterns throughout the experiment. Salt and mechanical processing had greater prooxidant effect on pressurized samples. Pre-treatment slurries presented more oxidation than post-treatment slurries. PMID- 22062659 TI - Using ActivaTM TG-RM to bind beef muscles after removal of excessive seam fat between the m. longissimus thoracis and m. spinalis dorsi and heavy connective tissue from within the m. infraspinatus. AB - Binding beef muscles together after removing excess seam fat and heavy connective tissue was studied. Ribeye rolls and top blade roasts were fabricated from corresponding sides of 24 beef carcasses with cuts from one side serving as treated (bonded) and cuts from the other side serving as controls. For the ribeye rolls, the bonded treatment consisted of removing the kernel fat that lies between the m. spinalis dorsi and the m. longissimus thoracis. For the top blade roasts, the bonded treatment consisted of removing the heavy connective tissue sheath after the m. infraspinatus was cut open lengthwise. To bind muscles together after removal of fat or connective tissue, a dry-sprinkle mixture of ActivaTM TG-RM (featuring the enzyme, transglutaminase) along with 5% sodium caseinate by weight was applied to the surfaces to be bonded (approximately 0.25% by weight was used). Steaks were cut for raw and cooked proximate analysis and energy assessment and for in-home and simulated retail case consumers studies. Bonded steaks were higher in dissectible lean, lower in energy from fat and total energy for all cuts, and higher in protein for the raw top blade, raw ribeye, and cooked ribeye steaks. Bonded ribeye steaks were lower in chemical and dissectible fat and higher in moisture. Consumers rated bonded ribeye steaks higher than control steaks for leanness and bonded top blade steaks higher for all raw appearance and cooked palatability traits. When asked to purchase bonded or control steaks from a simulated retail case, consumers purchased bonded ribeye steaks because of leanness and bonded top blade steaks because of perceived greater marbling compared to control steaks. Modifying subprimals to remove excessive seam fat and connective tissue resulted in improved physical and chemical composition of steaks and improved many visual and eating quality characteristics. PMID- 22062660 TI - Meat quality comparison of Berkshire, Duroc and crossbred pigs sired by Berkshire and Duroc. AB - The object of this study is to specify features determining meat quality of Berkshire and Duroc and influence of these purebreds on meat quality of crossbred pigs. In total, 37 purebred pigs (Berkshire and Duroc: originating from line breeding in Kagoshima Prefecture and Miyagi Prefecture, respectively) and two crossbreeds (LDB and LDD: produced by crossing Berkshire and Duroc boars to Duroc Landrace sows) were used. Berkshire accumulated more subcutaneous and abdominal fat and had small loin eye muscle area, but accumulated less intramuscular fat than Duroc. There were no differences in meat colour and tenderness between the two purebreds. But Berkshire was less than Duroc in drip loss. As for fatty acid of inner and outer subcutaneous fat, Berkshire contained significantly higher concentration of saturated fatty acids, but had lower concentration of unsaturated fatty acid than Duroc. As a result, the melting point of inner and outer subcutaneous fat and perirenal fat of Berkshire was significantly higher than that of Duroc. Furthermore, though there was no breed difference in concentration of saturated fatty acids of intramuscular fat, Duroc had more oleic acid (C18:1) than Berkshire. Fatty acid concentrations of inner and outer subcutaneous fat and intramuscular fat as well as melting points of both subcutaneous fat layers and perirenal fat were the same in Berkshire and LDB and in Duroc and LDD. These results suggest that there were remarkable differences between Berkshire and Duroc in fat quality traits; also, both breeds as terminal sires influenced crossbred pigs' fat accumulation and fat quality traits. PMID- 22062661 TI - Relationship among collagen amount, distribution and architecture in the M. longissimus thoracis and M. pectoralis profundus from pigs. AB - The relative distribution of types I and III collagens and collagen fibre architecture in the perimysium and endomysium were compared to the longissimus thoracis (LT) and pectoralis profundus (PP) muscles in pigs. The LT muscle was composed of type I myofibres 16.8%, IIA 12.9% and IIB 70.2%, and the PP muscle was 25.4, 23.1 and 51.5%, respectively. The total collagen amount differed significantly between the LT (2.66 mg/g) and PP (4.13 mg/g) muscle (P<0.001). On image analysis of the immunohistochemical preparations for types I and III collagens, the percentage area of the perimysium to the total collagen area showed significant differences between the muscles, where perimysial type I collagen occupied 25.4% of the total area in the LT muscle and 45.7% in the PP and perimysial type III 37.6 and 54.5%, respectively (P<0.001). In scanning electron microscopic photographs of the macerated preparation, very thick collagen layers composed of several fibre bands were observed in the perimysia of the PP muscle and appeared differently from the thinner perimysia with a few bands in the LT. Similar architecture of endomysial collagen fibres were observed around every myofibre type in the PP muscle and also in the LT. The fine surface cover of reticular collagen fibres around an adipocyte was shown as a global cast. These results suggested that the total collagen amount of the PP muscle was related mainly to the well developed perimysia composed of several collagen bands, indicating tougher meat compared with the LT muscle. PMID- 22062662 TI - Development and evaluation of a fermented cabrito snack stick product. AB - In order for the meat goat producer to survive, new avenues for marketing goats must be created. Currently, the live animal is sold directly to consumers, or to brokers who in turn sell the animal directly to consumers or retail stores that cater to various ethnic groups. The production of value-added products with appeal to North American consumers, as well as current ethnic consumers, should result in increased profitability of the meat goat. The objectives of this study were to develop a value added product, cabrito snack sticks, using goat meat as the sole meat ingredient; evaluate soy protein concentrate (SPC) at various levels in an effort to reduce the cost of the product; determine consumer acceptability of the product; and conduct a cost analysis to determine the approximate market price for the product. Three fermented cabrito snack stick products were manufactured containing either 0, 1.75 or 3.50% SPC and stored at 2+/-1 degrees C until evaluated. The snack sticks were evaluated for sensory characteristics, proximate analysis, pH, water activity and smokehouse yields. Trained panelists detected no significant flavor differences (P>0.05) between the products. As a result of these findings, snack sticks formulated with 0 and 3.50% SPC were compared in a consumer sensory evaluation. Consumer panelists detected no significant differences (P>0.05) in flavor, texture and overall acceptance between the snack stick products, and approximately 61% of the panelists commented that they would purchase them. Cabrito snack sticks formulated with 3.50% SPC had lower fat (P<0.05) and higher ash contents when compared with the control (0% SPC) sticks. Moisture, protein, water activity and smokehouse yields were similar (P>0.05) for both products. Moisture: protein ratio and pH values were higher (P<0.05) for snack sticks formulated with 3.5% SPC when compared with the control sticks. The addition of SPC resulted in a 4.60% reduction in the price of snack sticks formulated with 3.50% SPC when compared with control sticks. PMID- 22062663 TI - Evaluation of the antioxidant ability of hydrazine-purified and untreated commercial carnosine in beef patties. AB - The aim of this research was to reevaluate the inhibition of oxidative changes in beef patties packaged in modified atmosphere (70% O(2)+20% CO(2)+10% N(2)) by carnosine (50 mM). The need for reevaluation was because it had been postulated that hydrazine present as contaminant in commercial carnosine could contribute to the antioxidant activity. Beef patties with either commercial or purified hydrazine-free carnosine were stored at 2+/-1 degrees C for 20 days and evaluated for colour (a* and H*), TBARS, metmyoglobin formation (% of total surface myoglobin), psychrotrophic microbial counts and sensory odour. Results indicated that both forms of carnosine effectively inhibited lipid oxidation and color changes in beef patties throughout storage, showing no significant differences (P>0.05) between them. It was concluded that the antioxidant effect was brought about by the carnosine molecule and not by hydrazine. PMID- 22062664 TI - Changes of myofibrillar and centrifugal drip proteins and shear force of psoas major and minor and semitendinosus muscles from calves, heifers and cows during post-mortem ageing. AB - Changes in myofibrillar protein content and centrifugal drip proteins of psoas major and minor (PM) and semitendinosus (ST) muscles of calves, heifers and cows taken from carcasses on the 1st, 6th and 12th day of post-mortem cold storage were estimated. Washed myofibrils and centrifugal drip from muscles were analysed using SDS-PAGE 10 and 12% polyacrylamide gels. No significant changes were observed in content of contractile proteins, alpha-actinin and regulatory proteins (except for TN-T). There were no significant differences between muscles from investigated groups and between muscles aged in chilled conditions. The levels of titin T1 during ageing varied slightly. The 30 kDa-fraction appearance was fastest in calf, slower in heifer and slowest in cow muscles. More pronounced differences in the level of protein degradation with regards to muscle type, age of animals and time of storage were found in the centrifugal drip of meat. In the drip, the level of high molecular weight proteins was higher in muscles from young animals and in the muscles stored longer. The opposite was observed in case of 26-28 kDa proteins. Their amount in muscle drip decreased with increased storage time. The rate of proteolysis and release of cytoskeletal proteins during cold storage of muscles were related to change in shear values of roasted meat. The highest rate of protein degradation was observed in PM calf muscle and the lowest rate in ST cow muscle. The fastest tenderization process was registered in calves muscles and the slowest tenderization in cows. PMID- 22062665 TI - Changes in structure of psoas major and minor and semitendinosus muscles of calves, heifers and cows during post-mortem ageing. AB - Changes occurring during post-mortem ageing in structure of psoas major and minor (PM) and semitendinosus (ST) muscles of calves, heifers and cows were observed. Samples from muscles taken 3 h after slaughter and after 6 and 12 days of storage at the temperature of 4 degrees C were analysed using light and transmission electron microscopy. Three hours after slaughter muscle fibres were close to each other and sarcomeres showed normal structure of A- and I-bands, M-lines and Z disks. The space between myofibrils and sarcolemma and also between single myofibrils in muscle fibres increased during storage. Structure of sarcomeres underwent continuous degradation, length of sarcomeres increased due to enlargement of I-bands accompanied by Z-disk degradation. During ageing structural changes in myofibrils took place faster, were more intensive in muscles of younger animals and were more extensive and faster in PM than in ST muscles. PMID- 22062666 TI - Shear values of raw samples of 14 bovine muscles and their relation to muscle collagen characteristics. AB - Raw samples of 14 muscles: Mm. biceps femoris (BF), quadriceps femoris (CF), diaphragm (DI), flexor digitorum (FD), gluteus medius (GM), infraspinatus (IE), longissimus lumborum (LL), longissimus thoracis (LT), psoas major (PM), pectoralis profundus (PP), semimembranosus (SM), semitendinosus (ST), sternomandibularis (STER) and triceps brachii (TB) from four Swiss Brown (485+/ 15 days old) young bull carcasses and weighing approximately 300 kg were evaluated for some chemical and physical properties. PM (2.11 kg) and DI (2.24 kg) were the muscles which had the lowest Warner-Bratzler shear force values, while PP (6.66 kg) had the greatest shear force (P<0.05). FD and IE muscles had the highest concentration of total collagen content while PM and DI had the lowest (P<0.05) contents, TB and IE muscles presented the highest insoluble collagen concentration while PM and LT had the lowest (P<0.05) contents. High positive correlation between total collagen content and Warner-Bratzler shear force of raw samples was found (r=0.723; P<0.01) and between insoluble collagen content and Warner-Bratzler shear force was (r=0.661; P<0.01). Significant differences (P<0.05) were observed among muscles for differential scanning calorimetry, sarcomere length, pH and colour parameters. PMID- 22062667 TI - Relationships of myosin heavy chain fibre types to meat quality traits in traditional and modern pigs. AB - Porcine skeletal muscle fibres were molecularly classified, using in situ hybridisation and immunocytochemistry, into four types, according to the isoform of myosin heavy chain (MyHC) that was present in each fibre (MyHC slow/I, MyHC 2a, MyHC 2x and MyHC 2b). The relationship between MyHC fibre types and meat quality traits between two phenotypically divergent muscles [longissimus dorsi (LD) and psoas], and between the same muscles of different breeds (traditional Berkshire and Tamworth, and modern Duroc-based and Large White-based) were examined. We found that the greater abundance of fast oxidative-glycolytic MyHC 2a and 2x fibres in the psoas was associated with superior meat quality traits, and that the greater presence of fast glycolytic MyHC 2b fibres in the LD could account for less favourable quality traits, both in terms of pH, drip loss, grain, colour, yield force and work done. Although significant correlations were found between specific fibre types and quality traits, within either the psoas or LD muscle of some breeds, no consistent correlation was found across both muscles and all breeds. This finding was in line with the view that a given fibre type could have considerable differences in phenotype between breeds, and between muscles. The observed inverse compositional and functional-meat quality relationship between MyHC 2b and 2x fibres, and MyHC 2b and 2a fibres could form a basis of fibre type manipulation to improve meat quality. PMID- 22062669 TI - Reduction of Bacillus subtilis, Bacillus stearothermophilus and Streptococcus faecalis in meat batters by temperature-high hydrostatic pressure pasteurization. AB - People have a growing preference for fresh, healthy, palatable and nutritious meals and drinks. However, as food deterioration is a constant threat along the entire food chain, food preservation remains as necessary now as in the past. High pressure processing is one of the emerging technologies being studied as an alternative to the classical pasteurization and sterilization treatments of food. Samples of fried minced pork meat were inoculated with strains of Streptococcus faecalis and with sporulating microorganisms like Bacillus subtilis and stearothermophilus. The samples were subjected to several combined temperature high pressure treatments predicted by the mathematical model applied in Response Surface Methodology. Using the "Box-Behnken" concept, the number of tests for a whole area of pressure-temperature-time-combinations (pressure variation: 50-400 MPa, temperature variation 20-80 degrees C, time variation 1-60 min) could be limited to 15. In the center point of the model, the experimental combination was performed in triple to estimate the experimental variance. All the tests were executed in a randomized order to exclude the disturbing effect of environmental factors. Microbial analysis revealed for each microorganism an important reduction in total plate count, demonstrating a superior pressure resistance of the sporulating microorganisms in comparison with the most pressure resistant vegetative species Streptococcus faecalis. The effect of the medium composition could be neglected, showing little protective effect of, e.g. the fat fraction as seen in heat preservation techniques. PMID- 22062670 TI - The effect of stress during lairage and stunning on muscle metabolism and drip loss in Danish pork. AB - The effect on meat quality of a low stress handling system (LSS) compared with a traditional handling system (TS) was investigated in Duroc*(Landrace*Yorkshire; n=117) and (Hampshire*Duroc)*(Landrace*Yorkshire) pigs (n=110) under commercial conditions. In the low-stress handling system the pigs were kept in groups of 15 during lairage and movement up to the stunner. Before the stunner the groups were divided into three groups of five pigs for the CO(2)-stunning in a specially designed set-up. The pH and temperature were determined in m. longissimus dorsi (LD) and m. biceps femoris (BF) at various times post mortem. Immediately after exsanguination a biopsy was taken from the LD and analysed for the concentration of glycogen, lactate and creatine phosphate. The day after slaughter the pH was determined in the LD, BF, m. semimembranosus (SM) and m. semispinalis capitis (SC). The temperature was determined in the LD and BF, the internal reflectance was determined in the LD, SM and BF, the colour was determined in LD, the drip loss was determined in LD and BF, and the amount of blood splashing/bruising was evaluated in LD. There was a tendency for a higher concentration of creatine phosphate in the LSS-group (P=0.06). The pH in both the LD and BF on the day of slaughter decreased more slowly from 5 min post mortem to 40 min post mortem in the LSS-group than in the TS-group (P<0.001). From 40 min to 6 h post mortem the rate of the pH decline was similar in the two groups producing the lowest pH level in the TS group. The day after slaughter the pH was similar in the two groups in the LD and SC, whereas in the BF and SM it was lower in the LSS-group than in the TS-group. The drip loss was lower in the LSS-group in both LD (P<0.01) and BF (P<0.05) whereas the internal reflectance was only different in LD with the lowest value in the LSS-group (P<0.001). The lightness (L*) was higher in the LSS-group (P<0.05). There was no effect of stunning system on the amount of blood splashing/bruishing in the LD. The study showed that by using a low stress stunning system it is possible to decrease drip loss, possibly by increasing the concentration of creatine phosphate and thereby delaying the acceleration of pH fall in muscles after death. PMID- 22062671 TI - Effect of a dietary vitamin E supplementation on colour stability and lipid oxidation of air- and modified atmosphere-packaged beef. AB - The effects of dietary vitamin E supplementation on tissue alpha-tocopherol level and on the susceptibility of fresh and modified atmosphere-packaged beef on myoglobin and lipid oxidation were investigated. Charolais cattle, aged 32-44 months, were fed diets containing 75 (control, n=8) or 1000 mg (supplemented, n=8) alpha-tocopheryl acetate/kg feed/day for 111 days prior to slaughter. Following vacuum packaging, M. Longissimus lumborum and M. triceps brachii were aerobically packaged and held under refrigerated display (3 degrees C) for 9 days or packaged under modified atmosphere (MAP; 20% CO(2): 80%O(2)) and held under refrigerated display (8 degrees C) for 13 days under fluorescent light. alpha tocopherol concentrations were significantly higher (P<0.05) in meat from the supplemented group than from the basal one. Whatever the measured colour characteristics (a*, R(630)-R(580),% MetMb), the vitamin E supplementation had a positive but non-significant effect on the rate of discoloration. But by visual assessment, essentially with MAP, a significant and positive effect of vitamin E supplementation was noted to lower discoloration (P<0.05). TBARS values were significantly lowered (essentially at the end of storage time for the two packaged modes) after an alpha-tocopheryl acetate-supplementation. PMID- 22062672 TI - Contribution of pigment content, myoglobin forms and internal reflectance to the colour of pork loin and ham from pure breed pigs. AB - The colour of loin, M. longissimus dorsi (LD), and ham, M. biceps femoris (BF), from pure breed Hampshire, Swedish Landrace and Swedish Yorkshire pigs was studied. The contribution of the pigment content, the myoglobin forms deoxymyoglobin (Mb), oxymyoglobin (MbO) and metmyoglobin (MetMb) and the internal reflectance to the colour of pork of normal meat quality was evaluated using partial least squares regression (PLS). The colour of LD and BF from the Hampshire breed was more red and yellow and more saturated than the colour of the same muscles from the Swedish Landrace and the Swedish Yorkshire breeds. Furthermore, BF from Hampshire was darker than BF from the other two breeds. These differences in colour were related to the lower pH in Hampshire, resulting in more blooming and in higher internal reflectance, and to the higher pigment content. The colour of BF was darker and more red than the colour of LD within each breed. No colour difference was found between gilts and castrates within each breed. Most of the variation (86-90%) in lightness (L* value), redness (a* value) and yellowness (b* value), chroma (saturation) and hue angle of pork of normal meat quality was explained by the pigment content, myoglobin forms and internal reflectance. The L* value, a* value, chroma and hue angle were influenced by both the pigment content and by the myoglobin forms to almost the same extent, while the internal reflectance was of no significance to these colour parameters. The b* value was influenced most by the myoglobin forms, less by the internal reflectance and almost not at all by the pigment content. PMID- 22062673 TI - Marbling effects on quality characteristics of pork loin chops: consumer purchase intent, visual and sensory characteristics. AB - These studies evaluated whether consumers detect differences among pork loin chops with low (1.05% fat), medium (2.33%) and high (3.46%) amounts of marbling when visually evaluated, when prepared under controlled conditions, and when prepared at home. Highly marbled chops appeared lighter colored, less lean, had less acceptable appearance, and were less likely to be purchased than leaner chops; they were juicier, more tender, oily and flavorful than leaner chops. These results indicate a disparity between purchase intent based on visual evaluation, and quality attributes of the cooked product. When evaluated at home, consumers rated the chops they chose (40% low, 40% medium marbled) as more tender, juicy and flavorful than chops they evaluated "blind" on-site suggesting that additional factors have a significant impact on stated purchase intent. PMID- 22062674 TI - Comparison of destructively and rinsing gained samples to determine TVC of pig carcasses by bioluminescence. AB - A rinsing-technique with a spraying gun in combination with the ATP bioluminescence for determining the microbial load was investigated. In each case 3.8-cm(2) pig-rind was rinsed with buffered peptone water using a modified sprinkle-bottle. The sample-suspensions were gathered in a one-way syringe and sent through a filter cascade consisting of a coarse filter in order to remove bigger particles and a sensitive filter to attach the micro-organisms as well as somatic cells. This procedure was followed by an extraction of the ATP from the sensitive filter with CellSolver FBC-solution. The destructively gained samples were determined on their TVC by the conventional method. Results of the carcass surface spray test combined with bioluminescence compared to the conventional destructive method followed by plate-count showed a correlation r=0.93 with a detection limit down to 10(4) cfu/cm(2). PMID- 22062675 TI - Arcobacter spp. enumeration in poultry meat using a combined PCR-ELISA assay. AB - A rapid assay for enumeration of Arcobacter spp. in chicken meat was developed by using the polymerase chain reaction (PCR) coupled to an enzyme-linked immunosorbent assay (ELISA). Following a short selective enrichment of poultry samples, bacterial DNA was extracted and amplified using digoxigenin-labelled primers specific for 16S rRNA sequences of Arcobacter spp. Amplified fragments were heat denatured before being quantified by an ELISA. In this technique, a biotinylated probe immobilized onto streptavidin-coated microplates was used to capture the digoxigenin-PCR products. A peroxidase antidigoxigenin conjugate was added to the plate and, in the presence of substrate, PCR products were quantitated based on an optical density reading. Distinct absorbance differences were obtained when assaying poultry samples containing Arcobacter spp. in the range 10-10(4) CFU/g. PMID- 22062676 TI - Inhibition of protease activity. Part 1. The effect on tenderness and indicators of proteolysis in ovine muscle. AB - To examine the effect of particular enzyme groups on tenderness specific cysteine protease inhibitors were injected into muscle early post-mortem. The protease enzyme inhibitor E-64 was injected into the m. longissimus thoracis et lumborum (LTL) on the right side of 12 lamb carcasses within 15 min of death and in another 12 carcasses with the protease inhibitor Z-Phe-Ala-CHN(2). The left LTL (control) was injected with saline (0.25 M NaCl). To create variation in the rate of pH decline alternate carcasses were electrically stimulated (low voltage). The LTL was divided into cranial and caudal portions and aged for 1 or 2 days. Muscle samples at 1 day post-mortem were used for measurement of osmolality and sarcomere length (n=48), and others at 1 and 2 days post-mortem for shear force determination (n=96). The myofibrillar fragmentation index (MFI) was determined on samples taken at pH 6.2 and 1 and 2 days post-mortem (n=144). Other muscle samples were obtained at death, pH 6.2 and 6.0 and then at 1 and 2 days post mortem (n=215). These samples were used for determination of protein solubility and the concentration of free amino acids. Stimulation caused a faster (P<0.05) decline in pH. There was no effect of stimulation (P>0.05) on shear force values, but injection of inhibitor and ageing both had effects (P<0.001). The inhibitor E 64 prevented any improvement in tenderness with ageing, whereas the inhibitor Z Phe-Ala-CHN(2) and the control samples showed a similar ageing response. In the latter two treatments there was an average reduction of 1 kg in shear between 1 and 2 days post-mortem, whilst the inhibitor E-64 maintained shear force on average 2 kg higher than control samples. Injection and ageing had an effect on MFI (P<0.001) and there was an interaction (P<0.05) between stimulation and ageing for MFI, such that as stimulated muscle aged the rate of change of MFI was greater. There was an interaction between injection and ageing (P<0.05) for protein solubility such that samples treated with E-64 showed a minimal increase in protein solubility with ageing, whereas in samples treated with Z-Phe-Ala CHN(2) and the control samples there was a significant increase. There was also an interaction between stimulation and ageing such that between sampling at pH 6.0 and 2 days post-mortem, stimulated muscle exhibited greater solubility (P<0.05). There were no effects (P>0.05) on the concentration of free amino acids. The evidence indicated that the cysteine proteases were responsible for post-mortem proteolysis and tenderisation, in particular the calpains, whereas the cathepsins (B and L) were unlikely to contribute to proteolysis and subsequent tenderisation in meat. PMID- 22062677 TI - Effect of illumination source on the appearance of fresh meat cuts. AB - The effects of incandescent (INC), fluorescent (FL), and metal halide (MH) light sources on the appearance of fresh beef, pork and chicken meat were investigated. The color of all meats was more desired (P<0.05) when presented under an INC light source. The color used to describe beef meat presented under INC light was red, but dark brown or dark red under FL and MH. Relative luminance data, collected with a fiber optic probe connected to a photo diode array, demonstrated the reason to be a lack of redness in the commonly used FL and MH light sources. This difference was more pronounced in dark red beef cuts than in lighter pork and chicken cuts. PMID- 22062678 TI - Pressure-induced changes in the connectin/titin localization in the myofibrils revealed by immunoelectron microscopy. AB - Changes in the connectin/titin localization in post-mortem and pressurized chicken muscles were investigated by immunoelectron microscopy. The anti connectin monoclonal antibody, 1D11, strongly labeled the sides of thick filaments near the H-zone and weakly labeled the sides of Z-line in the sarcomere prepared immediately after death. With the development of the muscle contraction, the shortening of the sarcomere and the dispersion of the connectin epitope near the H-zone were observed. With the gradual increase of the sarcomere length during further storage, the apparent increase of the width of the epitope in the A-band region stained by the antibody was observed, but the distance from the epitope to M-line remained almost the same length. In the case of high pressure treatment, significant changes in the labeling pattern of the antibody were observed with the increase of the pressure applied. The increase of the distance from the epitope to M-line and dispersion of the epitope were observed in the fiber pressurized at 100 MPa. These phenomena were accelerated with the increase of the pressure applied. The discontinuous dense materials labeled by the antibody at the thick filament near the H-zone were observed in the fiber bundles pressurized at 200 MPa or more. This is probably due to the accumulation of connectin molecule from ordinary location in the sarcomere, because of the pressure-induced destruction of the thick and connectin filaments. In the fiber bundles pressurized at 300 MPa, a significant increase in the distance from the epitope to M-line accompanied with the increase of the sarcomere length was observed. From the results obtained, it was clear that the changes in the location of the connectin epitope induced by the brief exposure to high pressure were drastic in comparison with that in the sarcomere during post-mortem storage. PMID- 22062679 TI - Inhibition of protease activity 2. Degradation of myofibrillar proteins, myofibril examination and determination of free calcium levels. AB - The structure of muscle injected with specific cysteine protease inhibitors was examined to determine whether inhibitors cause denaturation and the degradation post-mortem of myofibrillar proteins was followed using SDS electrophoresis. Given the central role of calcium in theories of tenderisation the level of free calcium was measured during the early post-mortem period. The protease enzyme inhibitor E-64 was injected into the m. longissimus et thoracis lumborum (LTL) on the right side of 12 lamb carcasses within 15 min of death and in another 12 carcasses with the protease inhibitor Z-Phe-Ala-CHN(2). The left LTL (control) was injected with saline (0.25 M NaCl). Muscle samples were obtained at death, pH 6.2 and 6.0 and then at 1 and 2 days post-mortem (n=215). Muscle samples were selected from eight portions of the LTL (1-day post-mortem, from six different carcasses) for examination by transmission electron microscopy. Matching light images of myofibrils were obtained after determination of myofibrillar fragmentation. Free calcium concentration was determined for all samples (n=191) using an ion selective electrode excluding those 'at death'. Light images of myofibrils from treated samples showed normal striations and no evidence of denaturation or aggregation compared to control samples. This also applied to the samples processed for examination by electron microscopy. Appearance of the 30 kDa subunit increased with time (P<0.001) post-mortem. The interaction between ageing and stimulation had an effect (P<0.001) on the amount of a protein designated M1. The amount of M1 measured pre-rigor was greater for stimulated muscle, but the rate of decline was also greater through to day 2 post-mortem. Proteolysis was very rapid in the first 24 h post-mortem in ovine muscle. Ageing had an effect (P<0.001) on the free calcium concentration, which increased as muscle aged. As a covariate pH also had an effect (P< 0.05). Based on a non linear model when the concentration of free calcium reached a plateau (~110 MUM) the predicted pH was 5.5 (ultimate). From the qualitative observation of images and the levels of free calcium in injected muscle there is no support for the view that the inhibitors bind to sarcomere proteins, occupying sites to which calcium might bind. The levels of free calcium do not provide support for the view that m-calpain has a role in post-mortem tenderisation, but do suggest along with results of protein degradation that activation of MU-calpain is likely to occur before the pH drops to 6.2-6.1. PMID- 22062680 TI - Electrical stimulation of red deer (Cervus elaphus) carcasses - effects on rate of pH-decline, meat tenderness, colour stability and water-holding capacity. AB - A total of 14 female red deer were included in a study on the effects of low voltage carcass electrical stimulation on meat tenderness, colour stability and water-holding capacity. Carcasses were randomly allocated to either electrical stimulation treatment (ES; 90-95 V unipolar pulses, 7.5 ms duration, 15 Hz for a duration of 55 s) or no electrical stimulation (non-ES) (n=7 in each group). Temperature and pH decline was recorded in M.m. triceps brachii, longissimus dorsi et lumborum (at the last rib; LD) and biceps femoris, at intervals from 0.5 to 20 h post-mortem. At 24 h post-mortem, LD from the left side were excised, vacuum packaged and refrigerated at -1.5 degrees C. Glycogen concentrations, measured at 30 min post-mortem, and ultimate pH did not differ between groups. Compared to controls, ES increased the rate of muscle pH decline and produced lower shear forces at 1 day, 1 week and 3 weeks post-mortem, but these differences disappeared by 6 and 12 weeks post-mortem. Sarcomere lengths at 24 h post-mortem were unchanged by ES. After 1 week of refrigerated storage, ES significantly reduced display life (hours of Minolta a* value ? 12), but this difference disappeared at 3, 6 and 12 weeks of ageing. ES did not affect drip at any ageing time point. The present results demonstrate that the benefits of ES on tenderness are not permanent, and the procedure is not necessary for a long-term, chilled product. This study showed no detrimental effects of using electrical stimulation on meat colour stability or drip loss. PMID- 22062681 TI - Tailoring bystander CPR--a step too far? PMID- 22062682 TI - Cerebral oximetry - the holy grail of non-invasive cerebral perfusion monitoring in cardiac arrest or just a false dawn? PMID- 22062683 TI - Percutaneous cardiopulmonary support in pulmonary embolism with cardiac arrest. AB - OBJECTIVE: To assess the role of percutaneous cardiopulmonary support (PCPS) for the resuscitation of patients with massive pulmonary embolism (PE) with circulatory collapse. We also compared outcomes for PCPS between patients with massive PE with circulatory collapse and patients with AMI with cardiogenic shock. BACKGROUND: The effectiveness of PCPS for acute myocardial infarction (AMI) complicated with cardiogenic shock has been reported, but there are few reports on the use of PCPS for massive PE with circulatory collapse. METHOD: We studied 12 consecutive patients with massive PE and 16 patients with AMI, who required PCPS for resuscitation either during cardiopulmonary resuscitation (CPR) or after successful CPR. RESULTS: Twelve patients with PE and 16 patients with AMI were identified. There were no differences in age, the Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) score at admission, rate of cardiac arrest on arrival, and time from first circulatory collapse to PCPS between the two groups. However, the proportion of men with PE (33%) was smaller than those with AMI (87%, p<0.05). The duration of PCPS was shorter in PE (38 h) compared with AMI (83 h, p=0.051) patients. The proportion of patients successfully weaned from PCPS (100% vs. 37.5%, p<0.01), survival rate at discharge (83.3% vs. 12.5%, p<0.001) and good neurological outcome (58.3% vs. 6.3%, p=0.004) was significantly higher for PE compared to AMI patients. CONCLUSION: In our small case series, percutaneous cardiopulmonary support (PCPS) had a life saving role in patients with massive PE and cardiac arrest. PCPS was also more effective in patients with massive PE with cardiac arrest than in patients with AMI and cardiac arrest. PMID- 22062684 TI - Origin of Epilachnapaenulata defensive alkaloids: incorporation of [1-13C]-sodium acetate and [methyl-2H3]-stearic acid. AB - Ladybird beetles produce a large number of defensive alkaloids. Previous studies suggest that the structural diversity of these endogenous alkaloids can be traced to a common biosynthetic route based on the condensation of several acetate units. In this study, adults of Epilachna paenulata, a phytophagous neotropical species, were fed on diet enriched with potential precursors (sodium acetate, fatty acids and the amino acids lysine and ornithine) labeled with stable isotopes ((13)C, (2)H and (15)N). Labeled acetate was incorporated into the structurally related homotropane and piperidine alkaloids. The later also showed incorporation of [methyl-(2)H3] stearic acid. Our results hence support a fatty acid pathway for the biosynthesis of E. paenulata alkaloids. To our knowledge, this is the first report on the incorporation of a labeled fatty acid into a defensive piperidine alkaloid in insects. PMID- 22062685 TI - Reverse stridulatory wing motion produces highly resonant calls in a neotropical katydid (Orthoptera: Tettigoniidae: Pseudophyllinae). AB - This paper describes the biomechanics of an unusual form of wing stridulation in katydids, termed here 'reverse stridulation'. Male crickets and katydids produced sound to attract females by rubbing their forewings together. One of the wings bears a vein ventrally modified with teeth (a file), while the other harbours a scraper on its anal edge. The wings open and close in rhythmic cycles, but sound is usually produced during the closing phase as the scraper moves along the file. Scraper-tooth strikes create vibrations that are subsequently amplified by wing cells specialised in sound radiation. The sound produced is either resonant (pure tone) or non-resonant (broadband); these two forms vary across species, but resonant requires complex wing mechanics. Using a sensitive optical diode and high-speed video to examine wing motion, and Laser Doppler Vibrometry (LDV) to study wing resonances, I describe the mechanics of stridulation used by males of the neotropical katydid Ischnomela gracilis (Pseudophyllinae). Males sing with a pure tone at ca.15 kHz and, in contrast to most Ensifera using wing stridulation, produce sound during the opening phase of the wings. The stridulatory file exhibits evident adaptations for such reverse scraper motion. LDV recordings show that the wing cells resonate sharply at ca. 15 kHz. Recordings of wing motion suggest that during the opening phase, the scraper strikes nearly 15,000 teeth/s. Therefore, the song of this species is produced by resonance. The implications of such adaptations (reverse motion, file morphology, and wing resonance) are discussed. PMID- 22062687 TI - The mechanism of dynein motility: insight from crystal structures of the motor domain. AB - Dynein is a large cytoskeletal motor protein that belongs to the AAA+ (ATPases associated with diverse cellular activities) superfamily. While dynein has had a rich history of cellular research, its molecular mechanism of motility remains poorly understood. Here we describe recent X-ray crystallographic studies that reveal the architecture of dynein's catalytic ring, mechanical linker element, and microtubule binding domain. This structural information has given rise to new hypotheses on how the dynein motor domain might change its conformation in order to produce motility along microtubules. PMID- 22062686 TI - Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. AB - Hsp90 is an ATP dependent molecular chaperone protein which integrates multiple oncogenic pathways. As such, Hsp90 inhibition is a promising anti-cancer strategy. Several inhibitors that act on Hsp90 by binding to its N-terminal ATP pocket have entered clinical evaluation. Robust pre-clinical data suggested anti tumor activity in multiple cancer types. Clinically, encouraging results have been demonstrated in melanoma, acute myeloid leukemia, castrate refractory prostate cancer, non-small cell lung carcinoma and multiple myeloma. In breast cancer, proof-of-concept was demonstrated by first generation Hsp90 inhibitors in combination with trastuzumab mainly in human epidermal growth factor receptor 2 (HER2)+metastatic breast cancer. There are a multitude of second generation Hsp90 inhibitors currently under investigation. To date, however, there is no FDA approved Hsp90 inhibitor nor standardized assay to ascertain Hsp90 inhibition. This review summarizes the current status of both first and second generation Hsp90 inhibitors based on their chemical classification and stage of clinical development. It also discusses the pharmacodynamic assays currently implemented in clinic as well as other novel strategies aimed at enhancing the effectiveness of Hsp90 inhibitors. Ultimately, these efforts will aid in maximizing the full potential of this class of agents. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90). PMID- 22062688 TI - Durable Lotus-effect surfaces with hierarchical structure using micro- and nanosized hydrophobic silica particles. AB - Surfaces with a very high apparent water contact angle (CA) and low water contact angle hysteresis (CAH) exhibit many useful characteristics, among them extreme water repellency, low drag for fluid flow, and a self-cleaning effect. The leaf of the Lotus plant (Nelumbo nucifera) achieves these properties using a hierarchical structure with roughness on both the micro- and nanoscale. It is of great interest to create durable surfaces with the so-called "Lotus effect" for many important applications. In this study, hierarchically structured surfaces with Lotus-effect properties were fabricated using micro- and nanosized hydrophobic silica particles and a simple spray method. In addition, hierarchically structured surfaces were prepared by spraying a nanoparticulate coating over a micropatterned surface. To examine the similarities between surfaces using microparticles versus a uniform micropattern as the microstructure, CA and CAH were compared across a range of pitch values for the two types of microstructures. Wear experiments were performed using an atomic force microscope (AFM), a ball-on-flat tribometer, and a water jet apparatus to verify multiscale wear resistance. These surfaces have potential uses in engineering applications requiring Lotus-effect properties and high durability. PMID- 22062689 TI - Rapid tumoritropic accumulation of systemically injected plateloid particles and their biodistribution. AB - Nanoparticles for cancer therapy and imaging are designed to accumulate in the diseased tissue by exploiting the Enhanced Permeability and Retention (EPR) effect. This limits their size to about 100nm. Here, using intravital microscopy and elemental analysis, we compare the in vivo localization of particles with different geometries and demonstrate that plateloid particles preferentially accumulate within the tumor vasculature at unprecedented levels, independent of the EPR effect. In melanoma-bearing mice, 1000*400nm plateloid particles adhered to the tumor vasculature at about 5% and 10% of the injected dose per gram organ (ID/g) for untargeted and RGD-targeted particles respectively, and exhibited the highest tumor-to-liver accumulation ratios (0.22 and 0.35). Smaller and larger plateloid particles, as well as cylindroid particles, were more extensively sequestered by the liver, spleen, and lungs. Plateloid particles appeared well suited for taking advantage of hydrodynamic forces and interfacial interactions required for efficient tumoritropic accumulation, even without using specific targeting ligands. PMID- 22062690 TI - EphA2 targeting peptide tethered bioreducible poly(cystamine bisacrylamide diamino hexane) for the delivery of therapeutic pCMV-RAE-1gamma to pancreatic islets. AB - The pathogenesis of type-1 diabetes is complicated, and a clear, single mechanism has yet to be identified. Reports have indicated that the activating receptor NKG2D plays an important role in the development of disease. Exploiting a natural phenomenon observed in tumors, plasmid DNA encoding for a soluble ligand to NKG2D (sRAE-1gamma) was isolated and engineered into a plasmid expression system. A polymeric gene delivery system was developed to deliver the soluble RAE-1 plasmid locally to the pancreatic islets for the prevention of type-1 diabetes. The bioreducible cationic polymer poly(cystamine bisacrylamide-diamino hexane) (p(CBA DAH)) was modified with poly(ethylene glycol) (PEG) and the targeting peptide CHVLWSTRC, known to target the EphA2 and EphA4 receptors. The PEG serves to improve stability and tissue selectivity, while the peptide will target EphA2 and A4, overexpressed in the pancreatic microvasculature. The targeting polymer Eph PEG-p(CBA-DAH) shows selective uptake by the target cell line, indicative of the targeting properties that will be seen in systemic administration. Using the delivery system, the therapeutic plasmid can be delivered to the pancreas, reduce interactions between the beta-cells and infiltrating NKG2D positive lymphocytes, and effectively protect beta-cells from autoimmune destruction and prevent type 1 diabetes. PMID- 22062691 TI - Fluorescent penetration enhancers for transdermal applications. AB - Chemical penetration enhancers are often used to enhance transdermal drug delivery. However, the fundamental mechanisms that govern the interactions between penetration enhancers and skin are not fully understood. Therefore, the goal of this work was to identify naturally fluorescent penetration enhancers (FPEs) in order to utilize well-established fluorescence techniques to directly study the behavior of FPEs within skin. In this study, 12 fluorescent molecules with amphiphilic characteristics were evaluated as skin penetration enhancers. Eight of the molecules exhibited significant activity as skin penetration enhancers, determined using skin current enhancement ratios. In addition, to illustrate the novel, direct, and non-invasive visualization of the behavior of FPEs within skin, three case studies involving the use of two-photon fluorescence microscopy (TPM) are presented, including visualizing glycerol-mitigated and ultrasound-enhanced FPE skin penetration. Previous TPM studies have indirectly visualized the effect of penetration enhancers on the skin by using a fluorescent dye to probe the transdermal pathways of the enhancer. These effects can now be directly visualized and investigated using FPEs. Finally, future studies are proposed for generating FPE design principles. The combination of FPEs with fluorescence techniques represents a useful novel approach for obtaining physical insights on the behavior of penetration enhancers within the skin. PMID- 22062692 TI - Critical factors in the development of tumor-targeted anti-inflammatory nanomedicines. AB - Tumors are complex and dynamic assemblies of different cell types within an atypical/abnormal architecture. Tumor-associated macrophages, mast cells, dendritic cells, eosinophils, fibroblasts are present in and around tumors and contribute to an abundant, deregulated and long lasting chronic inflammation, a permissive microenvironment for tumor proliferation. The fact that tumor initiated inflammation overrides protective immunity and supports tumor development, combined with the successful strategy of liposomal drug targeting to tumor tissues, gave rise to a novel attractive antitumor therapeutic strategy: targeting anti-inflammatory drugs to tumors. As many natural bioactive compounds have anti-inflammatory properties and act by targeting multiple signaling pathways, their medicinal application involves the treatment of cancer. The nanoformulation into liposomes circumvents solubility, stability, bioavailability issues associated with these compounds, while promoting tumor drug accumulation. Liposomal formulations of resveratrol, carvacrol phosphate, pterostilbene phosphate, N-(3-oxo-dodecanoyl)-l-Homoserine lactone, caffeic acid and caffeic acid phenethyl ester (CAPE) were prepared and characterized. In vivo, B16F10 melanoma bearing mice seem not to be responsive to liposomal treatments of natural compounds. The specific combination of tumor model, drug delivery system and drug potency are crucial factors that should be considered in the development and evaluation of new nanomedicines for cancer-inflammation therapy, especially when translating from preclinical models. PMID- 22062693 TI - Erythropoietin gene delivery using an arginine-grafted bioreducible polymer system. AB - Erythropoietin (EPO) plays a key regulatory role in the formation of new red blood cells (RBCs). Erythropoietin may also have a role as a therapeutic agent to counteract ischemic injury in neural, cardiac and endothelial cells. One of the limitations preventing the therapeutic application of EPO is its short half-life. The goal of this study was to develop a gene delivery system for the prolonged and controlled release of EPO. The arginine grafted bioreducible polymer (ABP) and its PEGylated version, ABP-PEG10, were utilized to study the expression efficiency and therapeutic effectiveness of this erythropoietin gene delivery system in vitro. Poly(ethylene glycol) (PEG) modification of the ABP was employed to inhibit the particle aggregation resulting from the interactions between cationic polyplexes and the negatively charged proteins typically present in serum. Both the ABP and the ABP-PEG10 carriers demonstrated efficient transfection and long-term production of EPO in a variety of cell types. The expressed EPO protein stimulated hematopoietic progenitor cells to form significant numbers of cell colonies in vitro. These data confirm that this EPO gene delivery system using a bioreducible polymeric carrier, either ABP or ABP PEG 10, merits further testing as a potential therapeutic modality for a variety of clinically important disease states. PMID- 22062694 TI - Some neural and behavioural aspects of electrical and mechanical stunning in ostriches. AB - Different electrical and mechanical stunning procedures were studied in ostriches to determine the effectiveness of the method. Fifty-eight South-African Black ostriches were equipped with EEG electrodes and stunned with three different electrical head-only methods and with a new captive needle pistol, using air pressure. The first stunning procedure consists of two trials. In the first trial a total of 45 ostriches were stunned with a voltage of 200V (spiked electrodes) during 1s. Unfortunately, in 10 animals the electrodes were disconnected. A general epileptiform insult on the EEG followed by recovery was observed in 20 ostriches. Another eight animals died after recovery and five showed an iso electric line and were dead. The total duration of the insult was 25+/-10s. The measured current was 463+/-120mA. In the second trial a constant current of 400mA was administered to 13 ostriches. In one animal the electrodes were disconnected. Eight out of 12 animals showed a general epileptiform insult, two of them showed an iso-electric line and two did not show the characteristics of a general epileptiform insult. The total duration of the insult on the EEG was 21+/-8s. The measured current was 365+/-91mA and the voltage 191+/-27V. During the second stunning procedure four and seven ostriches were stunned with 200V (spiked electrodes) and 48V (blunt electrodes), respectively, during approx. 6s. They all died. In addition, a group of 20 ostriches stunned with captive needle pistol using air pressure showed unconsciousness after stunning by the appearance of theta and delta waves tending to an iso-electric line on the EEG trace. It is recommended to use at least 500mA to stun ostriches effectively and to use a short stun-stick interval or to kill them by a long stunning duration. The captive needle pistol, using air pressure, can be an alternative for electrical head-only stunning. PMID- 22062695 TI - Measurement and prediction of pork colour. AB - The extent to which instrumental colour determinations by FOPu (light scattering), Gofo (reflectance) and Labscan II (CIE L*, CIE a* and CIE b*, hue and chroma) are related to the Japanese colour grades was studied. Additionally, four on-line methods: pH1, FOP1, PQM1 (conductivity) and DDLT (Double Density Light Transmission, analogous to Capteur Gras/Maigre), were evaluated for their ability to predict subjectively and objectively colour. One hundred and twenty samples of m. longissimus thoracis et lumborum, from animals of different genotypes, were analysed. Of the instrumental colour determinations, CIE L* (r= 0.82), FOPu (r=-0.70) and Gofo (r=0.70) were best correlated with the Japanese colour scores. The Japanese colour grades could be predicted by the on-line instruments, pH1, FOP1, PQM1 and DDLT, with determination coefficients between 15 and 28%. Ultimate meat colour, determined by Japanese colour standards, FOPu, Gofo and CIE L*, was better predicted by DDLT than by the classic on-line instruments: FOP1, pH1 and PQM1, although the standard error of the estimate was similar for all instruments. This means that DDLT, although originally designed for estimating lean meat percentage, can additionally give information about meat quality, in particular colour. However, it must be stressed that the colour estimate by DDLT refers to a population of animals, rather than to individual pigs, because of the number of erroneously assigned samples. PMID- 22062696 TI - The influence of goat genotype on the production of Capretto and Chevon carcasses. 1. Growth and carcass characteristics. AB - Fifty buck kids from five goat genotypes, Boer * Angora (BA), Boer * Saanen (BS), Feral * Feral (FF), Saanen * Angora (SA) and Saanen * Feral (SF) were compared for production of Capretto and Chevon carcasses. BS and SF kids had significantly better average daily gain compared to other genotypes and took less time to reach the required liveweight for Capretto and Chevon production. The development of visceral organs was not influenced by genotype. Kids from dairy breeds (SA in case of Capretto and SF in case of the Chevon group) deposited more internal fat in comparison to other genotypes. Dressing percentage (based on empty body weight) of kids ranged from 50-55%. At the same liveweight, dressing percentage and eye muscle dimensions did not vary between genotypes. However, BS and SF kids produced longer carcasses. Subcutaneous fat thickness was significantly greater in Chevon carcasses from BA compared to other genotypes. A high correlation was found between fat thickness measured by ultrasound on the live animal and ruler measurement on the carcass at the 12/13th rib position. Based on growth and carcass characteristics BS and SF kids performed better than kids from other genotypes used in the present study. PMID- 22062697 TI - The influence of goat genotype on the production of Capretto and Chevon carcasses. 2. Meat quality. AB - The effect of five goat genotypes, Boer*Angora (BA), Boer*Saanen (BS), Feral*Feral (FF), Saanen x Angora (SA) and Saanen x Feral (SF) on the meat quality of Capretto and Chevon carcasses obtained from 50 buck kids, was assessed. Genotype had an influence on cooking loss and longissimus thoracis muscle colour coordinates (CIE L(*), a(*), b(*) values). BS kids from the Capretto group had paler muscle colour compared to other genotypes; pale muscle colour being required for Capretto carcasses. Total pigment concentration, fat colour, shear force values and sensory scores for flavour, tenderness, juiciness and overall acceptability did not differ significantly between genotypes. Muscle colour became darker and fat colour became more yellow with increasing animal age. Tenderness decreased with animal age as indicated by higher shear force values. Age had no significant influence on cooking loss and sensory scores. PMID- 22062698 TI - The influence of goat genotype on the production of Capretto and Chevon carcasses. 3. Dissected carcass composition. AB - The dissected composition from left sides of the carcasses obtained from 50 buck kids from five goat genotypes (10 kids/genotype), Boer x Angora (BA), Boer x Saanen (BS), Feral x Feral (FF), Saanen x Angora (SA) and Saanen x Feral (SF), was compared at two age groups. The muscle content of various primal cuts varied between 53 and 73% for Capretto and Chevon groups, with minor differences between genotypes. SA kids had significantly higher separable carcass fat compared to BS and SF for the Capretto group, while Chevon carcasses from BA and SF deposited more carcass fat than FF. The bone content (19-21%) of the carcass side did not differ significantly between genotypes for the Chevon group. The dissected carcass components (muscle, fat and bone) were significantly correlated with those components of most of the individual cuts. The percentage carcass muscle and fat increased and bone content decreased significantly with age. PMID- 22062699 TI - The influence of goat genotype on the production of Capretto and Chevon carcasses. 4. Chemical composition of muscle and fatty acid profiles of adipose tissue. AB - The chemical composition of muscle and the fatty acid composition of adipose tissue from the carcasses obtained from 50 buck kids from five genotypes (10 kids/genotype), Boer x Angora (BA), Boer x Saanen (BS), Feral x Feral (FF), Saanen x Angora (SA) and Saanen x Feral (SF) reared for Capretto and Chevon production, were compared. Genotype did not influence the chemical composition of muscle except for muscle from BA carcasses, which had significantly higher extractable fat content. The proportions of individual fatty acids differed significantly between genotypes for the Capretto kids. Adipose tissue from the Capretto group had a higher concentration of palmitic acid (31-34%), while the proportion of oleic acid (37-40%) was greater in the Chevon group. With an increase in age and resultant change in diet, the saturated fatty acid concentration decreased and the unsaturated fatty acid concentration increased. PMID- 22062700 TI - Effect on the cholesterol content of fresh lamb of supplementing the feed of Awassi ewes and lambs with Lactobacillus acidophilus. AB - Lactating ewes and their lambs were provided daily with two enteric capsules of a freeze-dried culture of selected strains of Lactobacillus acidophilus (1*10(9) colony-forming-units/dose), along with their normal diets, for a period of 120 days. Initially, the supplementation had a significant effect on the serum cholesterol levels of the suckling lambs, but the benefit was reduced after weaning. On slaughter at 120 days, the mean cholesterol concentrations in three cuts of lamb meat were reduced by over 20%, and that in the liver by ~18%. In the Middle East where the consumption of lamb is high, this reduction could be beneficial for the consumer, and it is suggested that the potential value of probiotic cultures in ruminant nutrition merits further attention. PMID- 22062701 TI - High voltage electrical stimulation: its effect on microbial contamination of lamb carcases in a commercial abattoir. AB - This study was designed to establish the effect of an abattoir's commercial high voltage electrical stimulator on lamb carcase microbial contamination, including TVC, coliform and Campylobacter colony counts. Over eight visits, batches of six lamb carcases were sampled using the wet and dry swab technique both before and after passage through a high voltage electrical stimulator. On each visit three of the carcases were sent through the electrical stimulator while it was operational (the treatment group) and three carcases were sent through when the electrical stimulator had its power turned off (the control group). The swabs were placed into maximum recovery diluent, transported 'on-ice' and held at 0 degrees C overnight before dilutions and plating out the following day. Too few coliform colonies were recovered for a meaningful analysis and no campylobacters were recovered. The total viable counts of the electrically stimulated and the control carcases were found not to be significantly different. PMID- 22062702 TI - Methodological approach to evaluate the effects of age at slaughter and storage temperature and time on sensory profile of lamb meat. AB - A methodological approach, that requires the use of an experimental design, the definition of a sensory profile and an appropriate statistic validation of sensory data, was developed, in order to evaluate the effects of some process variables, such as age at slaughter and storage time and temperature, on sensory characteristics of lamb meat. In this study factorial design (2(3)) was used. The first step was the definition of descriptive terms for determining the sensory profile of meat. A vocabulary of 10 descriptive terms of odour, flavour and texture was developed. Therefore, after an appropriate and rigorous training, a panel of 8 assessors evaluated the lamb products in triplicate using a 100 mm unstructured scale. The following step was the statistic validation of data. Sensory data for each attribute were submitted to a fixed analysis of variance. Results showed that even though the panel was trained, judgements differed among assessors, as demonstrated by the significant assessor x sample interaction which was found for most attributes. In order to minimise this effect, the sensory data were submitted to a mixed analysis of variance that allows the determination of panel performance and selection of significant attributes for sample discrimination. Eight attributes were selected. Finally, analysis of variance with age, frozen temperature and storage time as main effects, was performed on mean values of selected attributes. Meaty odour and flavour, cohesiveness and stringiness were negatively influenced by age, whereas tenderness and juiciness were positively influenced by age. Lamb odour and flavour were positively influenced by frozen temperature. At increasing storage time, meaty odour and flavour and juiciness increased. The descriptive analysis allowed an objective description of the products in terms of perceived sensory attributes. The fixed and mixed models of analysis of variance produced different results. A mixed model appeared to be suitable for validation of panel performances and selection of significant attributes for meat samples discrimination. PMID- 22062703 TI - Lipid and cholesterol oxidation products in dry-cured ham. AB - An investigation was carried out on oxidative processes in dry-cured hams. Sixteen hams of various ageing times were divided into lean and fat parts, simulating typical consumer habits. All samples underwent analysis of peroxide value (PV), rancidity index (TBARs), 5 cholesterol oxidation products (COPs) and, in the lean samples, proximate composition. While the lean part was rather unaffected by oxidation, the external fat contained some of COPs, TBARs and PV. Comparison of hams at different ageing times revealed that lipid oxidation was substantially unaffected by the time of processing. It is concluded that good manufacturing practice will generally prevent oxidative damage in the edible part of dried hams, even if very long ageing times are used. PMID- 22062704 TI - Dry fermented sausages made with a protease from Aspergillus oryzae and/or a starter culture. AB - Sausages with a starter culture (Lactobacillus plantarum + Staphylococcus carnosus), a protease (Fungal Protease from Solvay Enzymes) and both enzyme/starter were produced from the same raw matter under the same conditions for 15 days of ripening. The lowest pH values were found in Fungal/starter sausages. Significantly higher amounts of free amino acids (FAA) were seen in sausages containing enzyme from the 3rd day of ripening, whereas amino acids from peptides (PAA) were significantly higher only after 15 days of ripening. Enzyme addition gave rise to changes in 10 of the 15 FAA analyzed. Histidine was the main amino acid from the peptide fraction that increased in both sausages containing added enzyme. Although trained panelists detected some sensorial benefits in the sausages with added enzyme, the effects were not as marked as might have been expected. PMID- 22062705 TI - The influence of manufacturing and drying conditions on the survival and toxinogenesis of Staphylococcus aureus in two Spanish dry sausages (chorizo and salchichon). AB - The effects of formulation, starter culture and fermentation temperature on growth and synthesis of toxin A (SEA) and TNase by Staphylococcus aureus during fermentation and drying of Spanish chorizo were investigated. Inhibitory factors able to inhibit SEA synthesis in culture media were unable to prevent SEA production in chorizo fermented at 20 and 30 degrees C, though a lower temperature and starter culture SP318 (Lactobacillus sake, Pediococcus pentosaceous and Staphylococcus xylosus) decreased staphylococcal growth and SEA formation. Reduction and even disappearance of the SEA during ripening was observed. In most batches, TNase was a reliable indicator of staphylococcal growth and SEA production. Dextrose added to the salchichon formulation repressed S. aureus growth during drying. Lactobacillus curvatus in combination with dextrose was an effective anti-staphylococcal agent during fermentation. PMID- 22062706 TI - Effect of lupin seed proteins on quality characteristics of fermented sausages. AB - Lupin seed flours (LSF) and lupin seed protein isolates (LSPI) from a sweet (S) variety of Lupinus albus and a bitter (B) variety of Lupinus albus ssp. Graecus were used in the manufacture of fermented sausages at 2% level, based on the weight of meat and pork back fat, and hydrated to a protein/water ratio 1/4, to replace beef and pork meat on a protein to protein basis. LSF and LSPI had no effect (p>0.05) on the microbial counts, the pH, the moisture content and weight losses, the instrumentally measured colour numbers (L*, a*, b*), the firmness, the appearance and the sensory evaluated colour of fermented sausages. Fermented sausages produced with LSPI from the bitter variety had similar (p>0.05) sensory attributes to the control and lower (p<0.05) TBA values after the 28th day of storage. Fermented sausages produced with LSPI from the sweet variety had acceptable sensory attributes but TBA values higher than 1 mg of malonaldehyde/kg. LSF from both varieties had a high pro-oxidant effect and affected negatively the odour and taste of fermented sausages. PMID- 22062707 TI - Thermal gelation properties of surimi-like material made fromsheep meat. AB - Thermal gelation properties of surimi-like material made from sheep meat were investigated. The sheep meat was ground, washed 3 times at a meat to water ratio of 1:5 and dewatered by centrifugation. The effects of washing on the composition, functional properties and colour of the mince, were studied. The washing method resulted in a sharp reduction of the fat content and an increase of the water content and pH of the mince. Lightness (L*) and yellowness (b*) of the mince were improved by washing. A significant reduction (p<0.001) of a* (redness) value and a decrease in the a*/b* ratios and saturation index value of the washed mince were recorded. Gels were prepared from washed and unwashed mince after being blended with 2% NaCl and heated at 75 degrees C for 20 min. The washed mince produced excellent gels as measured by the fold test, elasticity modulus and the percentage recovery. The gels made of washed mince had lower expressible fluid compared to that of unwashed mince. A fibrous protein network structure was evidenced in the gel made from washed mince while observed under a transmission electron microscope. PMID- 22062708 TI - Use of isotope analysis to characterize meat fromIberian-breed swine. AB - We describe a method based on isotope analysis (delta(13)C) for characterization and differentiation of Iberian pork meat as a function of the diet of the animal. Using adipose tissue, it is possible to classify unknown samples in group of animals designated "acorn-fed", "recebo=mixed-fed" and "feed raised" according the delta(13)C value obtained, from the calibration straight line of y=-22.12 0.35x, with a correlation coefficient r=0.982 and s=0.10/00; where y=delta(13)C and x=arrobas of acorn and range forage received by the animals during the fattening period. Stress should be placed on the economic and industrial importance of Iberian-breed swine because the market prices of Iberian swine products depends on the classification of the animals according to the type of feeding regimen which they are subjected to. PMID- 22062709 TI - Cooking rate, pH and final endpoint temperature effects on color and cook loss of a lean ground beef model system. AB - To assess the effects of pH, heating rate and endpoint temperature on instrumental and visual color of ground beef, pH was adjusted to 5.2-6.4, samples were heated at 0.7 degrees C or 3 degrees C/min to 55, 60, 65, 70, 75 or 80 degrees C in a water bath. Cooking rate had no effect on cook loss, instrumental or visual color. Regression equations for linear, quadratic and/or cubic effects of pH and/or endpoint temperature were significant for most color indices. Amount of variance explained by the model and R(2) was increased by adding the calculated percentages of metmyoglobin and/or deoxymyoglobin to the regression models. The predicted sensory brownness score (0=very pink, 7.5=intermediate pink/brown, 15=intense brown) for samples with pH 5.75 cooked to 70 degrees C was 9.75. Samples with a pH of 5.5 achieved this brownness score at 67 degrees C. Samples with a pH of 5.2 achieved this brownness at 58 degrees C. PMID- 22062710 TI - Influence of ultimate pH on bovine meat tenderness during ageing. AB - The aim of this work was to evaluate the influence of ultimate pH and ageing at 2+/-2 degrees C on the tenderness of beef. The m.longissimus thoracis et lumborum from 23 young bulls excised at 28 h post mortem were grouped into: Normal (pH 5.5 to 5.8) moderate DFD (mod DFD) (5.80.05) differences in soluble collagen and myofibrillar protein solubility (MPS) at pH 5.5 were found between the pH groups at any time. The tenderness evaluated by both methods was significantly (p<0.05) related to MFI, MPS at pH 7.0, cooking loss and juiciness. Total and soluble collagen, sarcomere length, intramuscular fat and MPS at pH 5.5 were not significantly (p>0.05) related with tenderness. PMID- 22062711 TI - 52nd International Congress of Meat Science and Technology (52nd ICoMST), Dublin, Ireland, 13-18 August 2006. PMID- 22062712 TI - Understanding meat quality through the application of genomic and proteomic approaches. AB - During the past few decades, advances in molecular genetics have led to the identification of multiple genes or genetic markers associated with genes that affect traits of interest in livestock, including single genes of large effect and QTL (genomic regions that affect quantitative traits). Transcriptomics enables analysis of the complete set of RNA transcripts produced by the genome at a given time and provides a dynamic link between the genome, the proteome and the cellular phenotype. Through a functional genomics approach to understanding the molecular basis of meat quality, we can gain further insight into the complex interplay of gene expression events involved in the development of meat quality. Proteomics permits visualisation of the protein content of the cell under varying conditions, combining powerful separation techniques with highly sensitive analytical mass spectrometry. To date, both the human and bovine genome projects have advanced our understanding of gene expression and helped elucidate the function of large portions of the genome. Advantages from this research have permeated through to a broader spectrum of research including that of meat science. Meat quality is manifested through a complexity of events in the muscle and their interactions with many environmental stimuli in both the live animal and during the post-mortem period. A lot of progress has been made in our understanding of the biological processes that contribute to the delivery of consistent quality meat. Through the application of tools of genomics and proteomics we are gaining a deeper insight into these processes and their interaction with environmental factors. Knowledge gained from these approaches can be beneficial in defining and optimising management systems for quality, providing assurance of meat quality and in tailoring quality to suit market needs. PMID- 22062713 TI - Innovations in beef production systems that enhance the nutritional and health value of beef lipids and their relationship with meat quality. AB - Consumers are becoming more aware of the relationships between diet and health and this has increased consumer interest in the nutritional value of foods. This is impacting on the demand for foods which contain functional components that play important roles in health maintenance and disease prevention. For beef, much attention has been given to lipids. This paper reviews strategies for increasing the content of beneficial omega-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic acid (CLA) and reducing saturated fatty acids (SFA) in beef. Particular attention is given to intramuscular fat (IMF) and the relationships between fatty acid composition and key meat quality parameters including colour shelf life and sensory attributes. Despite the high levels of ruminal biohydrogenation of dietary PUFA, nutrition is the major route for increasing the content of beneficial fatty acids in beef. Feeding grass or concentrates containing linseed (rich in alpha-linolenic acid, 18:3n-3) in the diet increases the content of 18:3n-3 and its longer chain derivative eicosapentaenoic acid (EPA, 20:5n-3) in beef muscle and adipose tissue, resulting in a lower n-6:n-3 ratio. Grass feeding also increases docasahexaenoic acid (DHA, 22:6n-3). Feeding PUFA rich lipids which are protected from ruminal biohydrogenation result in further enhancement of the PUFA in meat with concomitant beneficial improvements in the ratio of polyunsaturated:saturated fatty acids (P:S ratio) and n-6:n-3 ratio. The main CLA isomer in beef is CLA cis-9, trans-11 and it is mainly associated with the triacylglycerol lipid fraction and therefore is positively correlated with level of fatness. The level of CLA cis-9, trans-11 in beef is related to (1) the amount of this isomer produced in the rumen and (2) synthesis in the tissue, by delta-9 desaturase, from ruminally produced trans vaccenic acid (18:1 trans-11; TVA). Feeding PUFA-rich diets increases the content of CLA cis-9, trans-11 in beef. Trans-fatty acids in foods are of rising importance and knowledge of the differential effects of the individual trans isomers is increasing. TVA is the major trans 18:1 isomer in beef and as the precursor for tissue CLA in both animals and man should be considered as a neutral or beneficial trans-isomer. Increasing the content of n-3 PUFA in beef can influence colour shelf life and sensory attributes of the meat. As the content of n-3 PUFA increases then sensory attributes such as "greasy" and "fishy" score higher and colour shelf life may be reduced. Under these situations, high levels of vitamin E are necessary to help stabilise the effects of incorporating high levels of long chain PUFA into meat. However, grass feeding not only increases n-3 PUFA and CLA but, due to its high content of vitamin E, colour shelf life is improved. It is evident that opportunities exist to enhance the content of health promoting fatty acids in beef and beef products offering opportunities to add value and contribute to market differentiation. However, it is imperative that these approaches to deliver "functional" attributes do not compromise on the health value (lipoperoxidation) or the taste of beef products. PMID- 22062714 TI - Contribution of postmortem muscle biochemistry to the delivery of consistent meat quality with particular focus on the calpain system. AB - Tenderness has been repeatedly reported as the most important quality aspect of meat. However, a number of studies have shown that a significant portion of retail meat can be considered tough. As a consequence, a significant consumer segment is willing to pay a premium for guaranteed tender meat. However, apart from measuring the shear force, there is no reliable method to predict tenderness. Most of the branded meat programs therefore attempt to ensure eating quality by controlling some of the factors that affect tenderness. Meat tenderness is determined by the amount and solubility of connective tissue, sarcomere shortening during rigor development, and postmortem proteolysis of myofibrillar and myofibrillar-associated proteins. Given the effect of postmortem proteolysis on the muscle ultrastructure, titin and desmin are likely key substrates that determine meat tenderness. A large number of studies have shown that the calpain proteolytic system plays a central role in postmortem proteolysis and tenderization. In skeletal muscle, the calpain system consists of at least three proteases, MU-calpain, m-calpain and calpain 3, and an inhibitor of MU- and m-calpain, calpastatin. When activated by calcium, the calpains not only degrade subtrates, but also autolyze, leading to loss of activity. m-Calpain does not autolyze in postmortem muscle and is therefore not involved in postmortem tenderization. Results from a number of studies, including a study on calpain 3 knockout mice, have shown that calpain 3 is also not involved in postmortem proteolysis. However, a large number of studies, including a study on MU-calpain knockout mice, have shown that MU-calpain is largely, if not solely, responsible for postmortem tenderization. Research efforts in this area should, therefore, focus on elucidation of regulation of MU-calpain activity in postmortem muscle. Discovering the mechanisms of MU-calpain activity regulation and methods to promote MU-calpain activity should have a dramatic effect on the ability of researchers to develop reliable methods to predict meat tenderness and on the meat industry to produce a consistently tender product. PMID- 22062715 TI - Revisiting the conversion of muscle into meat and the underlying mechanisms. AB - The conversion of muscle into meat is a complex process in which all mechanisms responsible for the development of meat qualities are very likely interdependent. Colour and flavour are thus both dependent on oxidative mechanisms. Oxidation and proteolysis are probably two processes involved in the development of meat tenderness. This paper reviewed the consequences of programmed cell death or apoptosis on muscle cells structure and biochemistry and on meat qualities as well. We therefore look at different new hypothesis susceptible to highlight the meat science field and provide new supports for a more dynamic meat research. One of them which would have appeared evident for our purpose since a decade, deals with the fact that, after animal bleeding, muscle cells have no other alternative to only enter the programmed cell death procedure or apoptosis. If we introduce an early phase corresponding to apoptosis, taking place before the rigor onset and overlapping it, we will see that the known consequences of that process bring forward possible answers to still unexplained observations. After an overview of the actual state-of-the-art in meat science, we will introduce the programmed cell death and its underlying mechanisms. We then described the strong analogies between the known consequences of apoptosis and the postmortem changes affecting a set of different muscle characteristics. PMID- 22062716 TI - Genetic and environmental effects on the muscle structure response post-mortem. AB - This paper reviewed the mechanisms by which glycolytic rate and pre-rigor stretching of muscle impact on meat quality. If muscle is free to shorten during the rigor process extremes in glycolytic rate can impact negatively on meat quality by inducing either cold or rigor shortening. Factors that contribute to variation in glycolytic rate include the glycogen concentration at slaughter and fibre type of the muscle. Glycolysis is highly sensitive to temperature, which is an important factor in heavy grain fed carcasses. An alternative solution to controlling glycolysis is to stretch the muscle pre-rigor so that it cannot shorten, thus providing an insurance against extremes in processing conditions. Results are presented which show a large reduction in variance (both additive and phenotypic) in tenderness caused by pre-rigor stretching. Whilst this did not impact on the heritability of shear force, it did reduce genotype differences. The implications of these results on the magnitude of genotype effects on tenderness is discussed. PMID- 22062717 TI - Role of quantitative risk assessment and food safety objectives in managing Listeria monocytogenes on ready-to-eat meats. AB - Listeria monocytogenes may be found on ready-to-eat (RTE) meats, posing a public health risk. To minimize the public health impact, an appropriate level of protection (ALOP) can be established for a population with respect to L. monocytogenes, and ideally should be based on a scientific assessment of the risk, as well as societal and economic factors. Food safety systems can be based on meeting the ALOP. Food safety objectives (FSO) provide a link between the ALOP and performance objectives that are established to control a foodborne hazard. An FSO can be used as a risk management tool for L. monocytogenes in RTE meats, as the FSO establishes the stringency of the measures being used to control the hazard, by specifying the frequency and/or cell number of the pathogen in the food that should not be exceeded at the time of consumption. Typically, this requires setting performance objectives or performance criteria at an earlier point in the food chain, to ensure that the product will meet the FSO. Establishing an FSO requires an assessment of the risk of the hazard to the population of interest. Risk management strategies such as use of HACCP systems and Good Manufacturing Practices can then be used to ensure that the FSO is met. PMID- 22062718 TI - A review of quantitative microbial risk assessment in the management of Escherichia coli O157:H7 on beef. AB - Since Escherichia coli O157:H7 first emerged as a food borne pathogen in the mid 1980s, it has been linked to many cases of food poisoning across the world. While multiple sources and routes of transmission for this pathogen are now recognised, beef and beef products remain an important vehicle of the pathogen and continue to be linked to outbreaks across the developed world. Much research has been directed at E. coli O157:H7 transmission, survival and control in the beef chain and this paper presents an overview of current knowledge on this pathogen in the beef chain from primary production through slaughter, processing, distribution, final preparation and cooking. In order to strategically manage E. coli O157:H7 and to devise approaches to reduce the public health risk posed, many national and international groups have applied quantitative risk assessment techniques to model the risk posed by E. coli O157:H7 in beef, particularly in ground/minced beef which is most often linked with infection. This paper reviews these quantitative risk assessments and their application in managing the risk posed by E. coli O157:H7 in beef. PMID- 22062719 TI - Pathogens on meat and infection in animals - Establishing a relationship using campylobacter and salmonella as examples. AB - A high proportion of human campylobacter and salmonella infections is likely to originate from farm animals, usually directly from the consumption of contaminated meat or milk. Surveillance shows that campylobacter and salmonella genotypes are shared between human case isolates, farm animals and foods, although with the latter there can be marked differences between infection frequency in live animals and contamination rates in raw foods. This is supported by a variety of data from around the world, using a range of different methods. In this paper the evidence for farm animals being the reservoir of human salmonella and campylobacter infection is presented. However, a note of caution is sounded about the complex nature of zoonotic diseases caused by these two pathogens. Thus, many salmonellas and campylobacter types found routinely in food animals do not appear to cause human infections. Is this and artefact of the surveillance and/or microbiological methods used or are some strains of these bacteria genuinely non-pathogenic in man? PMID- 22062720 TI - Emerging microbiological food safety issues related to meat. AB - Avian influenza viruses and antibiotic-resistant pathogens have become topics of current public health interest. This paper will focus on the significance of these pathogens to the meat industry as well as other emerging microbiological food safety topics likely to impact the meat industry. These include surveillance of foodborne pathogens, microbial source tracking, risk assessment, and human populations at increased risk of infection by foodborne microbes. These emerging issues will likely lead to even greater challenges to producing microbiologically safe meat products than the industry has ever experienced. However, accompanying such challenges will be innovative solutions that provide even greater public health protection to meat-containing foods. PMID- 22062721 TI - Past, current and potential utilisation of active and intelligent packaging systems for meat and muscle-based products: A review. AB - Interest in the use of active and intelligent packaging systems for meat and meat products has increased in recent years. Active packaging refers to the incorporation of additives into packaging systems with the aim of maintaining or extending meat product quality and shelf-life. Active packaging systems discussed include oxygen scavengers, carbon dioxide scavengers and emitters, moisture control agents and anti-microbial packaging technologies. Intelligent packaging systems are those that monitor the condition of packaged foods to give information regarding the quality of the packaged food during transport and storage. The potential of sensor technologies, indicators (including integrity, freshness and time-temperature (TTI) indicators) and radio frequency identification (RFID) are evaluated for potential use in meat and meat products. Recognition of the benefits of active and intelligent packaging technologies by the food industry, development of economically viable packaging systems and increased consumer acceptance is necessary for commercial realisation of these packaging technologies. PMID- 22062722 TI - Opportunities for bio-based packaging technologies to improve the quality and safety of fresh and further processed muscle foods. AB - It has been well documented that vacuum or modified atmosphere packaging materials, made from polyethylene- or other plastic-based materials, have been found to improve the stability and safety of raw or further processed muscle foods. However, recent research developments have demonstrated the feasibility, utilization, and commercial application of a variety of bio-based polymers or bio polymers made from a variety of materials, including renewable/sustainable agricultural commodities, and applied to muscle foods. A variety of these bio based materials have been shown to prevent moisture loss, drip, reduce lipid oxidation and improve flavor attributes, as well as enhancing the handling properties, color retention, and microbial stability of foods. With consumers demanding more environmentally friendly packaging and a desire for more natural products, bio-based films or bio-polymers will continue to play an important role in the food industry by improving the quality of many products, including fresh or further processed muscle foods. PMID- 22062723 TI - Industrial packaging developments for the global meat market. AB - Packaging companies must carefully monitor retail and consumer trends to best utilize, direct, or prioritize their research dollars in developing packaging and packaging systems to meet these demands. This paper reviews packaging developments that are resulting from numerous trends taking place in the meat industry and in the retail sector. Current case ready packaging solutions that meet the needs of retailers to reduce labor in the back of the retail stores, and the consumer needs for a fresh product with excellent quality and palatability are also discussed. It will also review the current packaging options that are being developed to help consumers battle their "time crunch" with ready meal solutions. Finally, the necessity to increase food safety or eliminate pathogens while producing a high quality product continues to drive packaging development. Current systems and packaging available for post packaging pasteurization will be discussed. PMID- 22062724 TI - Future trends and consumer lifestyles with regard to meat consumption. AB - Using the food-related lifestyle model as a conceptual framework, one possible trend each is discussed for the following four components of food-related lifestyle: quality aspects, ways of shopping, cooking methods, and purchase motives. These trends refer to the increasing use of extrinsic cues in quality perception, shopping fast and easy vs. shopping in specialized outlets, the role of convenience and meat avoidance in cooking, and the role of concerns about the meat production process in purchasing. Indicators for each of these trends are discussed. PMID- 22062725 TI - Pathways to increase consumer trust in meat as a safe and wholesome food. AB - This paper focuses on the effect of information about meat safety and wholesomeness on consumer trust based on several studies with data collected in Belgium. The research is grounded in the observation that despite the abundant rise of information through labelling, traceability systems and quality assurance schemes, the effect on consumer trust in meat as a safe and wholesome product is only limited. The overload and complexity of information on food products results in misunderstanding and misinterpretation. Functional traceability attributes such as organisational efficiency and chain monitoring are considered to be highly important but not as a basis for market segmentation. However, process traceability attributes such as origin and production method are of interest for particular market segments as a response to meat quality concerns. Quality assurance schemes and associated labels have a poor impact on consumers' perception. It is argued that the high interest of retailers in such schemes is driven by procurement management efficiency rather than safety or overall quality. Future research could concentrate on the distribution of costs and benefits associated with meat quality initiatives among the chain participants. PMID- 22062726 TI - Integrated technologies to enhance meat quality - An Australasian perspective. AB - Ensuring meat quality attributes meet the requirements of the diverse range of markets is a critical component for the continued success of the New Zealand and Australian meat industries. Developing cost-effective and flexible technologies to help meet this requirement is a central objective of a current Meat and Wool New Zealand and Meat and Livestock Australia funded programme. This initiative was developed three years ago; it is a collaborative programme that involves meat scientists, electrical engineers and commercial meat processors. To ensure this programme successfully delivers technologies and knowledge to the Australasian meat industry, the following strategies have been developed: measurement of meat quality attributes 'on-line' during processing; development of 'expert systems' that can integrate and interpret on-line measurements and development of quality related feedback systems from the market that can be fed back to producers; and, development of methods to manipulate structural and biochemical events in meat to create new commercial opportunities for both producers and processors. This paper gives an overview of some of the new technologies that have developed from this programme that are being used commercially or, are undergoing the final stages of commercial validation. PMID- 22062727 TI - Implementing a palatability assured critical control point (PACCP) approach to satisfy consumer demands. AB - A 5-year commercial trial was run to test a new retail-to-farm trading model focused on beef eating quality as assessed by consumers. Retail description and pricing was based on cooked eating quality outcomes, dispensing with conventional anatomical cut description. Eating quality prediction was obtained by extensive use of the Meat Standards Australia (MSA) prediction model, which assigns a palatability score for each muscle from a given carcass when cooked by various methods. Pricing from the retail store to the boning and fabrication operation and from there to the supplying farmer was based on a % of retail value basis, thereby providing a direct incentive for the entire chain to focus on consumer satisfaction. Extensive yield and quality recording was conducted, providing detailed data to all participants and highlighting the magnitude of true value differences between carcasses, often of very similar type and appearance. The trial was successful in that sales continued to increase throughout the period and it has continued as an expanding commercial venture. The novel offer of fresh beef and cooked beef meals resulted in balanced carcass disposal and enhanced value to consumers. Systems were successfully developed to manage the process through each segment of the supply chain. It is believed that the principles demonstrated have broader industry relevance and provide the potential to stimulate substantial innovation and to reposition beef as a more contemporary food category. There are challenges in adopting this philosophy however due to required changes in technical procedures, in educating consumers regarding a new product offer and, more particularly, in changing industry culture. PMID- 22062728 TI - Reducing salt: A challenge for the meat industry. AB - Intake of dietary sodium has been linked to hypertension and consequently increased risk of cardiovascular disease (CVD). The estimated cost of CVD to both the EU and US economies is ?169B and $403B, respectively. Currently the daily sodium adult intake is approximately three times the recommended daily allowance (Ireland and UK) and therefore public health and regulatory authorities are recommending reducing dietary intake of sodium to 2.4g (6g salt) per day. Processed meat products comprise one of the major sources of sodium in the form of sodium chloride (salt). Salt has an essential function in meat products in terms of flavour, texture and shelf-life. Apart from lowering the level of salt added to products there are a number of approaches to reduce the sodium content in processed foods including the use of salt substitutes, in particular, potassium chloride (KCl) in combination with masking agents, the use of flavour enhancers which enhance the saltiness of products when used with salt and finally optimising the physical form of salt so that it becomes more functional and taste bioavailable. The ultimate goal of ingredient suppliers and meat processors is to produce reduced sodium meat products that consumers can enjoy as part of an ongoing healthier diet and lifestyle. This article reviews some of the technological aspects of reduced salt meat products and how the meat and food ingredient industries are responding to this current health issue. PMID- 22062729 TI - Game and venison - meat for the modern consumer. AB - This review focuses on how game meat from southern Africa and venison that are increasingly being imported into Europe and the US addresses consumer issues as pertaining to production (wild, free range or intensive production) and harvesting methods, healthiness (chemical composition, particularly fatty acid composition), and traceability. Although African game meat species are farmed extensively, deer species are farmed using extensive to intensive production systems. However, the increasingly intensive production of the cervids and the accompanying practices associated with this (castration, velvetting, feeding of balanced diets, etc.) may have a negative impact in the near future on the consumer's perception of these animals. These alternative meat species are all harvested in a sustainable manner using acceptable methods. All these species have very low muscle fat contents consisting predominantly of structural lipid components (phospholipid and cholesterol) that have high proportions of polyunsaturated fatty acids. This results in the meat having desirable polyunsaturated:saturated and n-6:n-3 fatty acid ratios. The South African traceability system is discussed briefly as an example on how these exporting countries are able to address the requirements pertaining to the import of meat as stipulated by the European Economic Community. PMID- 22062730 TI - The role of meat as a source of n-3 polyunsaturated fatty acids in the human diet. AB - It is considered that consumption of very long chain (VLC, carbon chain length ?20) n-3 PUFAs in most Western populations is sub-optimal and benefits in relation to chronic disease would be gained from increased consumption. This review examines the current contribution that meat makes to dietary intake of VLC n-3 PUFA and given its current low contribution, how ruminant meat may be enriched. Enrichment both directly with VLC n-3 fatty acids and indirectly by increasing intake by the animals of alpha-linolenic acid (ALNA; C18:3 n-3) are considered. Since it now appears that dietary ALNA is a very limited source of VLC n-3 PUFA in humans, the indirect route is controversial but since some forages are rich sources of ALNA this route has many sustainability and environmental attractions. Consideration is also given to the increased concentrations of trans and conjugated fatty acids that will arise from enriching ruminant meat with PUFA. PMID- 22062731 TI - Strategies for designing novel functional meat products. AB - In recent years, much attention has been paid to physiological functions of foods due to increasing concerns for health. Although there has been limited information of physiological functions of meat until recently, several attractive meat-based bioactive compounds, such as carnosine, anserine, l-carnitine, conjugated linoleic acid, have been studied. Emphasizing these activities is one possible approach for improving the health image of meat and developing functional meat products. This article provides potential benefits of representative meat-based bioactive compounds on human health and an overview of meat-based functional products. Strategies for designing novel functional meat products utilizing bioactive peptides and/or probiotic bacteria, is also discussed. This article focuses particularly on the possibility of meat protein derived bioactive peptides, such as antihypertensive peptides. There are still some hurdles in developing and marketing novel functional meat products since such products are unconventional and consumers in many countries recognize meat and meat products to be bad for health. Along with accumulation of scientific data, there is an urgent need to inform consumers of the exact functional value of meat and meat products including novel functional foods. PMID- 22062732 TI - Crossbreeding dual-purpose cattle for beef production in tropical regions. AB - Six breed types groups of six steer calves each were used to observe differences in growth and carcass traits: F1 Brown Swiss (F1BS), F1 Holstein (F1HO), F2 Brahman (F2BR), F2 Criollo Rio Limon (F2CRL), purebred Criollo Rio Limon (CRL), and Perija Mosaic (PMO). After 404 days of grazing, the heaviest F1BS and F2BR steers were different from F1HO and CRL counterparts (p < 0.05) in slaughter weight. F2BR dressed higher and had better muscle conformation scores than F1BS, F1HO, F2CRL and CRL (p < 0.05). F1BS had the thickest backfat (0.5 cm) but only differed (p < 0.05) from F1HO (0.3 cm). Rib eye area, marbling score, carcass maturity, quality or yield grade, boneless cut percentages, bone percentage or percent trimmable fat did not vary among breed types. All steers were within the A maturity level and graded Standard. Results indicate the importance of feeding dual-purpose steers to heavier weights to please industry preferences. PMID- 22062733 TI - The role of endogenous proteases in the tenderisation of fast glycolysing muscle. AB - The activities of lysosomal cathepsins and the calpain-calpastatin system were measured to determine their involvement in the more rapid tenderisation of fast glycolysing muscle. The rate of pH fall of M. longissimus dorsi (LD) of Hereford cross Friesian heifers (n = 52, Experiment 1; n = 36, Experiment 2) was measured. Muscles were selected according to their rate of glycolysis; slow and fast (n = 16, Experiment 1; n = 10, Experiment 2). Fast glycolysing muscles were rated more tender in sensory analysis and had a lower shear force than slow glycolysing muscles. Slow glycolysing muscles had shorter sarcomere lengths. Low pH conditions in fast glycolysing muscle correlated with the enhanced release of cathepsins B and L from lysosomes. Calpain I activity was higher and calpastatin activity was lower in fast glycolysing muscle early post mortem. SDS-PAGE electrophoresis patterns showed increased proteolysis, such as the earlier appearance of the 30 kDa fragment in fast glycolysing muscle. Transmission Electron Microscopy (TEM) results showed a greater degree of ultrastructural breakdown early post mortem in fast glycolysing muscle. The results suggest that the increase in tenderness in muscles that undergo fast glycolysis early post mortem may be caused by proteolysis by released lysosomal cathepsins and calpain I uninhibited by calpastatin. PMID- 22062734 TI - Influence of the oxidative quality of dietary oil on broiler meat storage stability. AB - Broilers were fed a high fat diet containing 11% oil (9% rapeseed oil, 2% soya bean oil) and the oil was given either as fresh (peroxide value of 1 meqv. O(2)kg(-1) oil) or as highly oxidised (peroxide value of 156 meqv. O(2)kg(-1) oil). Diets were supplemented with 46 mg all-rac-alpha-tocopheryl acetate kg(-1) diet, resulting in a tocopherol content of 80.8 mg alpha-tocopherol and 58.6 mg gamma-tocopherol per kg diet in the fresh oil diet and of 44.0 mg alpha tocopherol and 18.3 mg gamma-tocopherol per kg diet in the oxidised oil diet, respectively, reflecting the degradation of the natural occurring tocopherols in the oxidised diet. Only minor differences were seen with respect to fatty acid composition in muscles from birds fed the two diets. The oxidation of the dietary oil lowered lipid stability significantly (p < 0.01) in both raw and precooked meats during chill storage, whereas only minor effects on the stability of frozen meat were seen. Tocopherol levels were significantly lower (p < 0.01) in muscles from birds fed the oxidised oil diet, explaining the decreased lipid stability of meat from these birds. Thigh meat was more susceptible to lipid oxidation during storage than breast meat, regardless of dietary treatment, although thigh meat had markedly higher tocopherol levels than breast meat. The molar ratio of PUFA > 18:2 (polyunsaturated fatty acids with three or more double bonds) to alpha tocopherol was significantly (p < 0.01) higher in thigh meat compared with breast meat, explaining the lower stability of the former during storage. PMID- 22062735 TI - Effect of natural antioxidants and vacuum packaging on the quality of buffalo meat nuggets during refrigerated storage. AB - Buffalo meat nuggets (BMN) were incorporated with 500 ppm sodium ascorbate, 10 ppm alpha-tocopherol acetate and 0.5% sodium tripolyphosphate while processing. There were three experimental groups of BMN, namely control aerobic packaged (CAP), treated aerobic packaged (TAP) and treated vacuum packaged (TVP), refrigerated and stored at 4 degrees C. It was observed that the treated samples (TAP and TVP) had significantly (p < 0.05) higher pH, W-B shear force, moisture and protein contents, sensory attributes and lower free fatty acids content in comparison to CAP samples. Vacuum packed nuggets (TVP) had significantly (p < 0.05) lower free fatty acid content, higher lactobacilli and total anaerobe counts and markedly higher scores for flavour and overall palatability, even at the 25th day of storage. Product quality reduced as storage time increased. Use of natural antioxidants and vacuum packaging extended the shelf life of BMN from 10 to 30 days under refrigerated storage. PMID- 22062736 TI - Effect of lactococcus lactis var. lactis biovar diacetylactis on bacterial counts, pH and total acidity of minced goat meat during refrigerated storage. AB - The mesophillic aerobic and psychrotrophic plate counts, pH and total acidity were determined in minced goat meat treated with Lactococcus lactis var. lactis biovar diacetylactis and stored at 4 degrees C. The inhibitory effect was pronounced when the initial contamination of the meat, particularly with psychrotrophs was low. Of pH and total acidity, pH was better correlated with microbial inhibition. There was development of odour (non-putrefactive) from the 4th day of storage reducing acceptability. PMID- 22062737 TI - Pig muscle fibre characteristics as a source of variation in eating quality. AB - Despite the application of the MLC Blueprint specifications there is still unacceptable variation in meat eating quality. Evidence from the literature suggests that the intrinsic characteristics of the muscle may be an important source of variation, but there is no indication as to what extent these characteristics may explain the residual variation in eating quality. The purpose of the present study was to quantify the role of muscle fibre characteristics in accounting for eating quality variability. In the study, evaluation of samples from 125 pigs from eight breeding company populations indicated that fibre characteristics, particularly the diameter of the fast twitch oxidative glycolytic fibres, contributed to variation in instrumental texture of meat. In addition, the data suggest that there are genetic differences in fibre type distribution which can be used to segregate populations. PMID- 22062738 TI - Role of amino acids and glucose in development of burnt off-flavours in liver sausage during heat processing. AB - The effect of amino acids and glucose on the development of burnt off-flavours was investigated in meat model systems for liver sausage. At a constant glucose concentration, the burnt flavour was intensified by addition of an amino acid mixture. In a batter without liver, the development of burnt off-flavours, similar to those in liver sausage, could be induced through addition of exogenous amino acids and glucose. The endogenous amino acids from liver reacted more intensely than the exogenous amino acids in the formation of the burnt flavour components. After heating batches with added exogenous amino acids and glucose the free amino acid contents (73-89% of initial content) were higher than in batches to which liver was added (42-53% of initial content). The differences in the free amino acid content of glycine, glutamic acid and threonine were linearly related to the intensity of burnt flavour. Results indicate that burnt flavour is due to the Maillard reaction. PMID- 22062739 TI - Technological suitability of mutton for meat cured products. AB - A comparative study on the technological suitability of mutton and pork for meat cured products was carried out. One type of cured dry sausages was made of mutton and the other of pork, using the same formulation and technological conditions. Thus, the evolution of physico-chemical and microbiological parameters, as well as colour and texture were measured at three different stages of the process: after mincing, after fermentation and after drying. The sensory parameters were assessed in the final product. Both mutton and pork had a similar technological aptitude during processing of cured dry sausages, with a similar evolution of the pH value, a(w) and Lactobacilli counts. The main differences between both types of sausage were observed in texture, colour and in the organoleptic characteristics, having mutton sausages greater cohesivity and more stable and redder colour than pork sausages. Besides, mutton sausages showed an aroma, flavour and texture that were not desirable for the panellists. PMID- 22062740 TI - Decontamination of carcasses by vacuum-hot water cleaning and steam pasteurizing during routine operations at a beef packing plant. AB - The microbiological effects of three operations for cleaning areas on dressed beef carcasses with vacuuming equipment which also applies hot water to the carcass, and of an operation for pasteurizing beef carcass sides with steam, were assessed. All four operations were routine in a commercial carcass dressing process. For each operation, swab samples were obtained from randomly selected carcasses, with a single sample being collected from each carcass, from a site selected at random from those affected by the operation. For the cleaning operations, 25 samples were obtained before and 25 after each operation. For the pasteurizing operation, 50 samples were obtained before and 50 after the operation. In addition, 50 samples were obtained from beef sides after the carcass cooling process which followed the pasteurizing operation. Total aerobic counts, coliforms and Escherichia coli from each sample were enumerated. The cleaning operations generally reduced the log mean numbers of bacteria on treated areas by <= 0.5 and had no discernible effect on the overall microbiological condition of the carcasses emerging from the process. The pasteurizing operation reduced the log mean numbers of total aerobic bacteria on carcasses by about 1, and the log mean numbers of coliforms and E. coli by > 2. The cooling process had no affect on the total counts, but further reduced the log mean numbers of coliforms and E. coli, apparently by about 1, to give beef sides from which E. coli were not recovered. PMID- 22062741 TI - Meat quality assessed Ante- and Post mortem by different ryanodine receptor gene status of pigs. AB - Different breeds and crossbreeds (total 63) of pigs with defined genotype (DNA based test on RYR 1 gene status) were divided in normal (non mutant), heterozygotes (carriers, monomutant) and homozygote positive (dimutant) animals. Muscle biopsy samples were taken at approximately 80 kg live weight using an efficient non-stress spring-loaded biopsy instrument. After incubation of muscle samples (39 degrees C, 1 hr) analyses pH, WHC (fluid), R value (ITP:ATP) were performed. After slaughter, meat quality values (pH(1), pH(24), R value, colour, drip loss) were also carried out. Heterozygotes were intermediate and between both homozygote pig groups in most meat quality values analysed. Using WHC (fluid volume) values (0.45 and 0.48 respectively) it was possible to divide heterozygotes into two groups, each closer to homozygotes. The values of pH, WHC (fluid), as measured at definite times on the biopsies, were correlated with the pH(1) post-mortem value (r approx 0.6-0.7). The results support previous findings on the possibility of differentiating pigs within DNA test-defined groups. Introducing the gene into a pig population could be useful, in improving leanness and muscling: but meat quality is certain to deteriorate. Further experiments are needed to support the possibility of identifying PSE-prone pigs from among normal non mutant pigs. PMID- 22062742 TI - Optimisation of calcium-dependent protease and cathepsin D assays in ostrich muscle and the effect of chemical and physical dry-curing parameters. AB - The best conditions for the assay of cathepsin D and Ca(2+)-dependent pro tease (CDP) activity in ostrich muscle was established in order to have a simple, rapid and reliable method for its determination. Measurements of A(280nm) of TCA soluble peptides and amino acid digests of casein and haemoglobin were used for measuring proteolytic activity in muscle extracts. The best conditions for the reliable determination of cathepsin D activity were found to be the incubation of an enzyme extract for 1 hr at 55 degrees C in a reaction mixture containing 0.9% (w v ) haemoglobin in 50 mM sodium formate buffer, pH 3.7. Characterization of the assay system for CDPs, obtained after phenyl-Sepharose chromatography, indicated that proteolytic degradation of casein by CDPs was linear with time up to 30 min at 30 degrees C and up to 0.1 units of activity. The effect of NaCl, KCl, nitrate, ascorbic acid, phosphate, glucose and sucrose on ostrich muscle CDP and cathepsin D activities has been studied. Salt (NaCl and KCl) acts as a strong inhibitor of proteolytic activity. Sodium and potassium nitrates (in the range 0 1000 mg l(-1)) affected activity to varying degrees. CDP activity was enhanced by sodium nitrate concentrations below 700 mg l(-1) and unchanged by potassium nitrate. Cathepsin D activity was inhibited to some extent by sodium nitrate above 200 mg l(-1) and completely by potassium nitrate. Results showed that phosphate is an inhibitor of both activities. High concentrations of ascorbic acid (above 6 g l(-1)) inhibited cathepsin D activity. Glucose (up to 2g l(-1)) activated cathepsin D activity and inhibited CDP activity (up to 1 g l(-1)). Sucrose activated enzyme activities at very low concentrations (1 * 10(-3) M) and inhibited activities above 1 * 10(-3) M. PMID- 22062743 TI - Supranutritional vitamin E supplementation in pigs: Influence on subcellular deposition of alpha-tocopherol and on oxidative stability by conventional and derivative spectrophotometry. AB - The influence of three levels of vitamin E (30, 200 and 1000mg kg(-1)) in the diet of pigs on the subcellular deposition of alpha-tocopherol in muscle and on the oxidative stability determined by conventional and first derivative Spectrophotometry was studied. The content of alpha-tocopherol in m. gluteo biceps and in mitochondrial and microsomal fractions of the muscle significantly increased (p < 0.01) with increasing levels of dietary vitamin E. Concentrations of alpha-tocopherol in muscle, mitochondria and microsomes of pigs fed diet supplemented with 1000 mg kg(-1) alpha-tocopheryl acetate were 3.2-, 6.1- and 5.6 fold greater, respectively, than those in their counterparts from the control animals. These differences in alpha-tocopherol concentration in the subcellular fractions and intact muscle resulted in enhanced stability of the membranes and the tissue when exposed to iron-ascorbate induced peroxidation. When lipid oxidation in the same samples was further measured by the first derivative method, the resultant MDA-TBA values were 59-69% lower in tissue samples, 16-19% lower in mitochondria and 6-9% lower in microsomes than the conventional TBARS values. PMID- 22062744 TI - Histo- and biochemical characteristics of the Longissimus dorsi muscle in pigs and their relationships to performance and meat quality. AB - Histo- and biochemical characteristics of the longissimus dorsi muscle at 65-70 kg body weight and their relationships to performance and meat quality at 100 kg were examined in Danish Landrace and Danish Large White female and castrated male pigs. Breed differences were observed for feed conversion rate, and a number of histochemical and biochemical traits. The organoleptic traits, flavour (13%), tenderness (15%) and overall acceptability (13%) were rated higher in Large White pigs. Significant correlations between histological and biochemical traits of the live muscle on the one side and performance, meat quality and organoleptic traits on the other side, could be demonstrated. However, these correlations were generally low (r < 0.35), and can thus only explain a small part of the variation in the measured quality traits. Consequently live muscle traits measured at 65-70 kg are poor predictors of meat quality characteristics after slaughter at 100 kg. PMID- 22062745 TI - Variation in post-mortem rate of glycolyis does not necessarily affect drip loss of non-stimulated veal. AB - In this study the effect of the rate of post mortem pH fall on the water-holding capacity of meat from moderately chilled veal carcasses was investigated. Also the relationship between muscle protein denaturation and drip loss of veal was examined. Three groups of 10 Friesian Holstein male veal calves each were selected on the basis of their pH in M. longissimus thoracis et lumborum (LTL) at 3 hr post mortem (pH(3)): (1) fast pH-fall, pH(3) < 6.2; (2) intermediate pH fall, 6.5 < pH(3) < 6.6; (3) slow pH-fall, pH(3) > 6.7. After 48 hr of chilling the LTL was excised from the carcass and sampled for determination of drip loss, filter paper wetness, sarcomere length, protein solubility and transmission value. Differences in pH(3) were not associated with differences in drip loss, filter paper wetness or differences in protein denaturation. It is suggested that at the relatively high veal carcass chilling rate the effect of rate of pH-fall on protein denaturation and thus on drip loss is negligible. Drip loss of veal was highly correlated with both solubility of sarcoplasmic (r = -0.67; p < 0.001) and total muscle protein (r = -0.54; p < 0.01) and with transmission values (r = 0.66; p < 0.001). These results indicate that protein denaturation measurements may be a good predictor for drip loss of veal. PMID- 22062746 TI - Chemical attributes characterizing sticky post-mortem ageing in beef. AB - Reports in literature on post-mortem sticky ageing are rare and data about chemical metabolites that occur particularly during sticky ageing are partly contradictory. In the present study different chemicals (pH, NH(3), TVB-N, H(2)S, R value, IMP, pyruvate and various volatile acids such as lactic acid, acetic acid, butyric acid, uric acid and pyroglutamic acid) were tested for their suitability to serve as parameters to characterize sticky post-mortem ageing in beef muscle samples. Results show that a high butyric acid concentration (0.46 MUMol g(-1)) seems to be typical for sticky post-mortem ageing in beef. A distinction from onset of spoilage is possible due to the high butyric acid concentration, a low ammonia content (10.5 mg 100 g(-1)) and a low pH value. From meat with normal ageing it can be differentiated by sensory, colour, smell, consistency, a high butyric and pyroglutamic acid content and a low IMP concentration (0.04 MUMol g(-1)). PMID- 22062747 TI - Estimation of factors influencing fatty acid profiles in light lambs. AB - Fatty acid composition of intramuscular, intermuscular, subcutaneous, omental and kidney knob fat depots of eighty male light lambs (+/-21kg live weight) from five Spanish sheep breeds was analysed. Fat depot, anatomical depot location (internal, external and intramuscular), breed (Spanish Merino, Grazalema Merino, Churra Lebrijana, Segurena and Montesina), weaning type (weaning at 45 days after birth or no weaning) and subcutaneous fat thickness factors were analyzed using a statistical model to quantify their contribution to the variation of each fatty acid. Production system was the main factor to explain variations in overall fatty acid profiles (34.68%). However, for several fatty acids and indices (arachidonic, linoleic, PUFA, n-3/n-6) anatomical depot location was the most significant factor. Feeding system explained 65.49% of CLA variance, indicating a strong influence of suckling period length on CLA deposition in lambs' fat. Moreover, due to the lack of interaction between anatomical depot location or depot and breed type or weaning system for total CLA, for future research only one depot would be enough to study the effect of those factors on CLA levels. PMID- 22062748 TI - The influence of early post-mortem enhancement and accelerated chilling on pork quality. AB - To improve pork quality, the effectiveness of early post-mortem enhancement and accelerated chilling were investigated. The four treatments evaluated were: Enhancement with Accelerated Chilling (ENAC), Accelerated Chilling Only (ACO), Enhancement with Conventional Chilling (ENCC), and Conventional Chilling Only (CCO). ENAC had a higher (P<0.05) pH than all other treatments. CCO resulted in the highest (lightest; P<0.05) L(*), while ENAC had the lowest L(*) value (darkest; P<0.05). Subjective color and striping did not differ (P>0.05) between ENAC and ENCC, although ENAC was numerically higher for both parameters. Sensory analysis for juiciness and tenderness were not different (P>0.05) between ENAC and ENCC, but both were higher (P<0.05) than ACO and CCO. Enhancement early post mortem coupled with accelerated chilling may be used to improve instrumental color and pH over conventional processing methods. PMID- 22062749 TI - Effect of dietary oregano oil supplementation on lamb meat characteristics. AB - The effect of dietary oregano essential oil supplementation on lamb meat characteristics was investigated. Eight male and eight female Chios lambs were divided into two equal groups. The first group was fed with the control diet consisting of concentrated feed and alfalfa hay, whereas the second group consumed the same diet, the only difference being that the concentrated feed was uniformly sprayed with oregano essential oil (1ml/kg). Duration of the experimental period was two months. No differences were observed after oregano essential oil supplementation in final body weight (kg), body weight gain (g) and carcass yield (%). Tenderness of longissimus thoracis muscle, expressed as sarcomere length and shear force value, was not influenced by the treatment, whereas pH and colour parameters (yellowness-redness) appeared to increase (P<0.05). Moreover, results showed that dietary incorporation of oregano essential oil exerted strong antioxidant effects retarding lipid oxidation (MDA formation) in meat during refrigerated and long-term frozen storage (P<0.001). PMID- 22062750 TI - Comparison of the compositional, microbiological, biochemical and volatile profile characteristics of three Italian PDO fermented sausages. AB - Three Italian PDO fermented sausages, Varzi, Brianza and Piacentino, were compared for compositional, microbiological, biochemical and volatile profile characteristics. Mean values for the gross composition varied especially due to moisture, fat, total protein and nitrate concentration which reflected differences in the ingredients and some technological parameters. Cell numbers of the major microbial groups were almost similar among sausages. The major differences were found for Brochothrix thermosphacta, enterococci and moulds. Apart from their use as starters, Lactobacillus sakei and Lactobacillus curvatus were the dominant lactic acid bacteria and, as well as Staphylococcus xylosus, dominated the population of coagulase-negative staphylococci. Sausages differed for the hydrolysis of myofibrillar proteins and secondary proteolysis. Varzi, the sausage subjected to prolonged fermentation at 23-25 degrees C for 10 days before ripening, showed the highest degree of secondary proteolysis. Varzi and Brianza, the two fermented sausages manufactured by using microbial starters, showed the highest concentration and similar profiles of free amino acids. The peptidase activities contained in the aqueous extracts agreed with the above findings. A total of 52 volatile components, mainly alcohols, aldehydes and terpenes, were identified by solid-phase micro-extraction coupled with gas chromatography-mass spectrometry analysis. The volatile profiles of the three Italian PDO fermented sausages differed in part and, except for terpenes, the highest levels of the other chemical classes were found in Varzi and Brianza sausages. The composition of free fatty acids of the three Italian PDO sausages was rather similar. Monounsaturated fatty acids (MUFA) were found at the highest relative percentage followed by saturated (SFA) and polyunsaturated (PUFA) fatty acids. Oleic, palmitic, linoleic and stearic were the main free fatty acids found in all fermented sausages. PMID- 22062751 TI - Effect of glucono-delta-lactone and kappa-carrageenan combined with high pressure treatment on the physico-chemical properties of restructured pork. AB - In this study, response surface methodology (RSM) was used to evaluate the combined effects of NaCl, glucono-delta-lactone (GdL), and kappa-carrageenan concentration (0.25%, 0.5%, and 0.75%) on the binding properties of restructured pork under hydrostatic pressure. All the generated RSM models showed no lack-of fit and significance at the 0.001 level. The addition of both NaCl and GdL had a significant effect on color. A significant decrease in pH was shown when the GdL level increased, and subsequently led to a decrease in WHC. However, increasing the GdL level increased the binding strength. Therefore, the results indicate that a reduction in the NaCl level during meat restructuring, under pressure treatment, can be achieved by using GdL; and even a low GdL concentration allows for palatable binding properties in meat restructuring when kappa-carrageenan is added. PMID- 22062752 TI - Effects of data expression, sample location, and oxygen partial pressure on initial nitric oxide metmyoglobin formation and metmyoglobin-reducing-activity measurement in beef muscle. AB - Methodology for measuring surface and subsurface metmyoglobin-reducing activity (MRA) of beef longissimus lumborum, semimembranosus, and psoas major was evaluated by submerging samples from the upper one half of 2.54cm thick steaks in 0.3% NO(2)(-), vacuum packaging, and incubating at 30 degrees C for 2h to promote pigment reduction. Initial metmyoglobin formation (IMF) and post-reduction metmyoglobin (PRM) were measured and used to calculate relative and absolute MRA values. The subsurface of all muscles maintained more (P<0.05) reducing capacity after 6d of display than the surface. Subsurface MRA was not significantly (P>0.05) correlated with surface colour stability whereas IMF was most correlated with colour stability (|r|>0.77; P<0.05). Longissimus steaks packaged in 20% O(2) had more (P<0.05) surface MRA than steaks packaged in 80% O(2) although measurement of MRA for steaks packaged in high-oxygen with this methodology is questioned. Determination of IMF is a better indicator of MRA for steaks exposed to atmospheric O(2) than more traditional measurements based on the amount of pigment reduced over time. PMID- 22062753 TI - A sensory description of boar taint and the effects of crude and dried chicory roots (Cichorium intybus L.) and inulin feeding in male and female pork. AB - Sensory profiling studies were carried out to evaluate the effects of chicory root (Cichorium intybus L.) and inulin bioactive feeding with respect to reducing the 'off-flavour' boar taint in intact male and female pork Longissimus dorsi and Psoas major. Feeding treatments significantly reduced perceived sensory boar taint in the cooked pork meat of intact males in both muscles. There were also indications that crude chicory was also effective in taint descriptor reduction in female pork, however not to the same systematic level as in male animals. Chemical measurements for skatole and androstenone were highly predictive of specific sensory descriptors of boar taint reduction. Feeding of crude, dried chicory and inulin were also determined not to impart negative sensory characteristics upon boar taint reduction. Chicory feeding therefore must be considered to have the potential for utilisation as part of a strategy for boar taint reduction in intact male pork. PMID- 22062754 TI - Water-soluble precursors of beef flavour. Part II: Effect of post-mortem conditioning. AB - Changes in glycolytic metabolites, nucleotide degradation products, free amino acids and other amino compounds were monitored in beef muscle (M. longissimus lumborum), stored for 21days at 4 degrees C, in order to evaluate how post-mortem conditioning may affect flavour formation in beef. The major effects observed in sugar-related substances were the dephosphorylation of the phosphates of glucose, fructose and mannose, to yield their free sugars, as well as the breakdown of inosine 5'-monophosphate, to give a sixfold increase in ribose. Total reducing sugars increased by only 15% during conditioning, while glycogen levels remained unchanged from 2days post-slaughter. Free amino acids increased during conditioning, particularly between days 7 and 14. Phenylalanine, methionine, lysine, leucine and isoleucine were the amino acids showing the greatest increase with conditioning time, with methionine, in particular, showing a sevenfold increase during the conditioning period. The effects of these precursor changes on cooked beef flavour are discussed. PMID- 22062755 TI - The effects of transglutaminase on the functional properties of the myofibrillar protein concentrate obtained from beef heart. AB - The aim of the present study was to evaluate the effect of bacterial transglutaminase on the functional properties of the myofibrillar protein concentrate from beef heart. The degrees of hydration and aggregation and emulsifying properties were studied. The degree of polymerization of the myofibrillar proteins depended on the enzyme concentration and setting time; the best results in terms of functional properties were obtained with 0.3g transglutaminase/100g protein with 60min setting at 35 degrees C. This investigation confirms that transglutaminase may be used for the production of myofibrillar protein aggregates with enhanced functional properties. PMID- 22062756 TI - False aneurysms in carotid arteries of cattle and water buffalo during shechita and halal slaughter. AB - It has previously been shown that the cattle brain is supplied with blood via a basi-occipital plexus, in addition to branches from the carotid and basilar arteries. In addition it has been shown during conventional stunning and slaughter that the carotid arteries in cattle can develop false aneurysms at their severed ends and this can curtail exsanguination. This investigation examined whether false aneurysms can occur during religious slaughter, and during bleeding following electrical stunning that simultaneously induced a cardiac arrest. The prevalence of large (>3cm outer diameter) false aneurysms in cattle carotid arteries was 10% for both shechita and halal slaughter. The prevalence of animals with bilateral false aneurysms (at least 2cm in one artery and at least 3cm diameter in the opposite artery) was 7% and 8% for shechita and halal slaughter, respectively. No false aneurysms occurred during bleeding in cattle that were electrically stunned and simultaneously developed a cardiac arrest. The combination of false aneurysms and collateral routes to the brain present a risk of sustained consciousness during religious slaughter in cattle. PMID- 22062757 TI - Real-time PCR for detection and quantification of red deer (Cervus elaphus), fallow deer (Dama dama), and roe deer (Capreolus capreolus) in meat mixtures. AB - A rapid real-time polymerase chain reaction (PCR) technique using SYBR Green detection system, has been developed for the quantification of red deer, fallow deer, and roe deer DNAs in meat mixtures. The method combines the use of cervid specific primers that amplify a 134, 169, and 120bp of the 12S rRNA gene fragment of red deer, fallow deer and roe deer, respectively, and universal primers that amplify a 140bp fragment on the nuclear 18S rRNA gene from eukaryotic DNA. The C(t) (threshold cycle) values obtained with the 18S rRNA primers are used to normalize those obtained from each of the cervid-specific systems, serving as endogenous control for the total content of PCR-amplifiable DNA in the sample. Analysis of experimental raw and heat treated binary mixtures of red deer, fallow deer or roe deer meat in a swine meat matrix demonstrated the suitability of the assay for the detection and quantification of the target cervid DNAs in the range 0.1-0.8%, depending on the species and treatment of the meat samples analyzed. PMID- 22062758 TI - The protective effect of electrical stimulation and wrapping on beef tenderness at high pre rigor temperatures. AB - A three factorial experimental design involving electrical stimulation (ES/NES), wrapping (wrapped/unwrapped) and pre rigor temperature (15 degrees C or 35 degrees C) was applied to 70 beef M. longissimus lumborum muscles to obtain a wide variation in shear force and drip loss. The shear force of all treatment groups decreased during ageing. As anticipated, wrapping and electrical stimulation had positive effects on shear force. However, high pre rigor temperature (35 degrees C) did not result in higher shear force values if the muscles were electrically stimulated, wrapped or both. The results suggested that electrical stimulation protects against the negative effects of high pre rigor temperatures. The drip loss of all treatment groups increased during ageing in a manner that was unrelated to treatment but was correlated to tenderness (r(2)=0.70; p<0.0001). It was concluded that the application of electrical stimulation, whatever the pre rigor temperature, protects beef from toughening through the prevention of rigor shortening and the avoidance of inhibition of ageing enzymes. PMID- 22062759 TI - Influences of dietary conjugated linoleic acid (CLA) and total lysine content on growth, carcass characteristics and meat quality of heavy pigs. AB - To assess the effects of dietary CLA, lysine and sex on performance, blood metabolites, carcass characteristics, meat quality and skeletal development, seventy-two pigs (initially 105.3+/-6.6kg live weight) barrows and gilts, were assigned to one of four diets in a 2*2*2 factorial arrangement. The diets contained 0% or 0.75% CLA, and 0% or 0.16% of l-lysine-HCl. All pigs were slaughtered at an average weight of 153.4+/-11.0kg. Neither CLA nor lysine supplementation influenced growth, blood metabolites or carcass characteristics. CLA reduced (P<0.05) pH(24) and increased (P<0.01) yellowness (b(*)) of the Longissimus muscle. Lysine increased (P<0.01) pH(24) and reduced (P<0.01) muscle ash content. CLA reduced (P<0.05) collagen synthesis, and lysine increased (P<0.05) collagen synthesis in Longissimus muscle, but no influence on intramuscular collagen maturity or muscle hydroxylysylpyridinoline crosslink concentration were observed. In addition, metacarpal bone diameter was reduced (P<0.05) by CLA. Barrows had higher ADG, final weight (P<0.01), carcass weight, lean percentage (P<0.05), serum cholesterol (P<0.05) and triacylglycerol (P<0.001) than gilts. Metatarsal diameter was larger in gilts than barrows (P<0.05). PMID- 22062760 TI - The impact of lactic acid concentration and sodium chloride on pH, water-holding capacity, and cooked color of injection-enhanced dark-cutting beef. AB - The objectives of this study were to evaluate the effect of enhancement with 0.5%, 1.0%, 1.5%, or 2.0% lactic acid (LA), with or without 0.5% salt (NaCl), on pH, water-holding capacity, and resultant cooked color of dark-cutting (DC) beef. The pH of DC sections treated with LA decreased (P<0.05), whereas water-holding capacity (WHC) increased (P<0.05) with increasing concentrations of LA. Sensory panelists noted an increase (P<0.05) in the degree of doneness (less pink internal color), whereas, a(*) and chroma values were lower (P<0.05), and hue angles were greater (P<0.05), indicating the internal color of LA-treated DC sections was less red and appeared more well-done. Also, 630:580nm reflectance ratios were similar (P>0.05) among DC steaks treated with 0.5% and 1.0% LA and normal pH (NDC) steaks, likely caused by an increase (P<0.05) in myoglobin denaturation in LA-enhanced DC steaks. These results indicate that the use of LA can reduce postmortem muscle pH and alter the cooked color of DC beef, ultimately resulting in a deletion of the persistent pinking condition. PMID- 22062761 TI - Biologically active polyamines in pig kidneys and spleen: Content after slaughter and changes during cold storage and cooking. AB - Polyamines putrescine, spermidine (SPD) and spermine (SPM) were determined as dansyl derivatives using an HPLC method. Distribution of SPD and SPM in pair kidneys was homogenous. The mean SPD and SPM contents in pig kidneys 24h after slaughter were 9.39+/-3.35 and 53.1+/-14.0mgkg(-1), respectively with no significant differences between barrows and gilts. Putrescine content was below the detection limit of 1.2mgkg(-1). In kidneys stored aerobically or vacuum packaged at 2-3 degrees C for 7 and 21 days, respectively, SPD and SPM decreased significantly. Stewing decreased both polyamines more extensively in kidneys processed on day-1 after slaughter than on day-7 after storage at 2-3 degrees C. The mean SPD and SPM in 10 spleens 24h after slaughter were 36.7+/-5.70 and 34.0+/-7.64mgkg(-1), respectively. Thus, both pork kidney and spleen are foods with a high level of SPM and SPD. PMID- 22062762 TI - Influence of various preservatives on the quality of minced beef under modified atmosphere at chilled storage. AB - The effect of preservatives on microbial quality, pH, drip-loss, roasting-loss, colour, and sensorial properties of modified atmosphere packaged (70% O(2) and 30% CO(2)) minced beef (M. semimembranosus) stored at (2+/-0.5 degrees C) for 12days was investigated. Beef cubes (approx. 20*20*20mm size) were immersed in solutions of 2% and 5% lactic acid, 2% lactic acid combined with 0.5% sodium ascorbate, 20% potassium lactate and 20% potassium sorbate before mincing. Addition of lactic acid was associated with pH drop, which increased drip-loss and roasting-loss. Application of all additives inhibited aerobic micro-organisms (10(3)-10(4)CFUg(-1) on day 12) compared to reference sample (9*10(5)CFUg(-1) on day 12). Lactic acid discoloured samples, while sodium ascorbate seemed to improve colour stability. Despite good visual colour characteristics, potassium sorbate treated samples were organoleptically unacceptable with massive off flavour. PMID- 22062763 TI - The effect of grazing saltbush with a barley supplement on the carcass and eating quality of sheepmeat. AB - The carcass and eating quality of sheep grazing a saltbush dominant saline pasture system or on a 'control' dry pasture, stubble plot both supplemented with barley for 14 weeks was investigated (Experiment 1, 50 (2*25) 6 month merino lamb wethers and Experiment 2, 50 (2*25) 18 month old merino hogget wethers). Treatment had no significant effect on eating quality attributes (P>0.05). Saltbush grazed sheep in both experiments had a significantly (P<0.01) lower carcass fat and significantly higher lean (P<0.01) content than the control grazed sheep. This is a positive finding as fat denudation is a significant cost to processors. The long term consumption of saltbush and barley prior to slaughter did increase muscle fluid content (P<0.05) but did not result in a decreased carcass weight loss at slaughter due to confounding changes in body composition. Grazing saltbush resulted in increased urine weight (P<0.001) and decreased urine concentration (P<0.05) at slaughter indicating an improved hydration status at slaughter. However both experiments demonstrated sub-optimal liveweight gains indicating that saltbush with a barley supplement can still be effectively used as a maintenance ration without compromising carcass and eating quality. PMID- 22062764 TI - Effect of concentrate feeding pattern in a grass silage/concentrate beef finishing system on performance, selected carcass and meat quality characteristics. AB - Steers were offered grass silage ad libitum and 6.4 kg concentrates daily for 126 days or silage ad libitum for 35 days, followed by concentrates ad libitum (Experiment 1). Steers were offered grass silage ad libitum and 6 kg concentrates daily for 154 days, concentrates ad libitum or grass silage ad libitum for 112 days followed by concentrates ad libitum (Experiment 2). All treatments received the same total concentrate allowance. In Experiment 1, there was no difference in any measurement of meat quality. In Experiment 2, ad libitum concentrate feeding per se, decreased redness and increased shear force of muscle at 2 days post mortem. Delaying concentrate feeding decreased fat yellowness, decreased shear force at 7 and 14 days post-mortem and increased muscle redness at 14 days post mortem. Modifications of the beef production system examined had minor effects on beef quality which are unlikely to be of commercial significance. PMID- 22062765 TI - Physical and sensory meat quality of South African Black ostriches (Struthio camelus var. domesticus), Zimbabwean Blue ostriches (Struthio camelus australis) and their hybrid. AB - Meat derived from three genotypes of ostrich, resulting from breeding South African Black (Black) ostriches and Zimbabwean Blue (Blue) ostriches as well as their hybrid, was analysed for physical and sensory quality. Ostriches of a commercially standard slaughter age of 14 months, raised under the same environment were used. The pH(24) was the highest in the pure Blue genotype and therefore meat from this genotype was the darkest and the percentage drip loss and cooking loss the lowest. When comparing the pure Blue genotype to the pure Black genotype, 70% of the muscles had a higher pH(24), 50% of the muscles were redder and significantly less saturated in colour, 67% of the muscles had a lower percentage drip loss and 50% of the muscles had a lower percentage cooking loss. No significant genotypic differences were found regarding the instrumental toughness, nor the sensory attributes of the meat. PMID- 22062766 TI - The genetic relationship between enzymatic activity of cathepsin B and firmness of dry-cured hams. AB - This study aimed to investigate the genetic relationship between enzymatic activity of raw hams and firmness of dry-cured hams. Instrumental firmness and sensory panel firmness scores were obtained from 2058 and 3275 dry-cured hams, respectively. On a sub-sample of 988 raw hams for dry-curing, enzymatic activity of cathepsin B was determined through a fluorimetric analytical method. A multiple-trait animal model was used to estimate heritability and genetic correlations of these traits. Estimates of heritability were moderate, ranging from 0.11 for sensory panel firmness scores to 0.25 for cathepsin B activity. Genetic correlations between firmness measures on dry-cured hams and enzymatic activity of raw hams were low. The efficiency of a selection program aimed to reduce the incidence of excessive softness in dry-cured hams on the basis of enzymatic activity of cathepsin B of raw hams is expected to be very limited. PMID- 22062767 TI - Effect of days on concentrate feed on sensory off-flavor score, off-flavor descriptor and fatty acid profiles for selected muscles from cull beef cows. AB - The effects of short-term realimentation (0, 42 or 84 days) of cull beef cows (n=24) and post-mortem aging (10 or 20 days) of selected muscles on sensory off flavor score, off-flavor descriptors of m. Gluteus medius (GLM), m. Longissimus lumborum (LOL), m. Triceps brachii-long head (LON) and m. Rectus femoris (REF) and fatty acid profiles (GLM, LOL and LON) were researched. Post-mortem aging did not affect sensory off-flavor detection or the interaction with muscle or treatment (P?0.65). Sensory off-flavor scores were lower (P<0.01) for steaks that were derived from cull cows fed a concentrate diet for at least 42days. As well, the number of samples that had detectable off-flavors decreased (P<0.01) when cull cows were fed for 42days. Realimentation did have an effect on fatty acid profiles (P<0.05). However, regression analysis showed changes in sensory off flavor score were not influenced (P>0.05) by alterations in fatty acid profiles. PMID- 22062768 TI - AMP-activated protein kinase is negatively associated with intramuscular fat content in longissimus dorsi muscle of beef cattle. AB - Marbling, or intramuscular fat, is an important factor in meat quality. As a key regulator of lipid metabolism, AMP activated protein kinase (AMPK) may be associated with intramuscular fat accumulation. Our objective was to evaluate the relationship among AMPK and its associated signaling mediators, with marbling and lean growth in beef cattle. Steers with high intramuscular fat content (High IMF, 5.71+/-0.36%, n=5) and low intramuscular fat content (Low IMF, 2.09+/-0.19%, n=5) were selected. High IMF was associated with increased tenderness (P<0.05) and backfat thickness (P<0.01). Muscle weights were higher in Low compared to High IMF (P<0.05). High IMF steers had a reduced AMPK activity (P<0.01), reduced acetyl-CoA carboxylase phosphorylation (P<0.05), and reduced total mTOR (P=0.02) content. Data provide evidence that AMPK is involved in IMF deposition in beef cattle. PMID- 22062769 TI - Allelic polymorphism of the caprine calpastatin (CAST) gene identified by PCR SSCP. AB - Calpastatin (CAST) specifically inhibits calpains and there is evidence that it plays a role in meat tenderization and myogenesis. Although the CAST gene has been extensively investigated in sheep and cattle, no studies have been reported in goats. In this study, a fragment of caprine CAST was analyzed using PCR-SSCP analysis. Seven novel SSCP patterns, representing seven different nucleotide sequences, were identified. All the sequences shared high homology with the published ovine and bovine CAST sequences. Sequence analysis revealed non synonymous amino acid variation in exon 6, which would result in a Ser/Arg substitution in domain L of the protein. Considerable variation was detected in an intron region close to the acceptor splice site, with both sequence variation and length variation being observed in this region. Variation detected here might have an impact on both the function and expression of caprine CAST. PMID- 22062770 TI - Genomic imbalances in endometrial adenocarcinomas - comparison of DNA ploidy, karyotyping and comparative genomic hybridization. AB - DNA ploidy analysis is useful for prognostication in cancer patients, but the genomic details underlying ploidy changes are not fully understood. To improve this understanding, we compared DNA ploidy status with karyotypic and comparative genomic hybridization data on 51 endometrial adenocarcinomas. Out of 34 DNA diploid tumors evaluated by CGH, 16 (47%) showed imbalances, though only two had more than four copy number changes. Ten (29%) had aberrations involving chromosome 1, seven (21%) involving chromosome 10, while one tumor had a chromosome 8 aberration. Four of the seven DNA tetraploid tumors (57%) had imbalances detected by CGH with two (29%) having more than four. Six out of eight DNA aneuploid tumors showed imbalances by CGH, with five (63%) having more than four. The aberrations were observed on chromosomes 1 and 8 in five/eight (63%) cases while four imbalances (50%) involved chromosomes 5, 7 and X. Not surprisingly, we observed a significant correlation between increasing DNA ploidy complexity and increasing number of copy alterations. Gains of material from chromosomes 8 and 7 might be specifically correlated to DNA aneuploidy in endometrial adenocarcinomas since 63% and 50% of the aneuploid compared to 3% of the diploid tumors showed imbalances involving these chromosomes. PMID- 22062771 TI - Increased efficiency of the GABAA and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome. AB - Cognitive impairment in Down syndrome (DS) involves the hippocampus. In the Ts65Dn mouse model of DS, deficits in hippocampus-dependent learning and synaptic plasticity were linked to enhanced inhibition. However, the mechanistic basis of changes in inhibitory efficiency remains largely unexplored, and efficiency of the GABAergic synaptic neurotransmission has not yet been investigated in direct electrophysiological experiments. To investigate this important feature of neurobiology of DS, we examined synaptic and molecular properties of the GABAergic system in the dentate gyrus (DG) of adult Ts65Dn mice. Both GABAA and GABAB receptor-mediated components of evoked inhibitory postsynaptic currents (IPSCs) were significantly increased in Ts65Dn vs. control (2N) DG granule cells. These changes were unaccompanied by alterations in hippocampal levels of GABAA (alpha1, alpha2, alpha3, alpha5 and gamma2) or GABAB (Gbr1a and Gbr1b) receptor subunits. Immunoreactivity for GAD65, a marker for GABAergic terminals, was also unchanged. In contrast, there was a marked change in functional parameters of GABAergic synapses. Paired stimulations showed reduced paired-pulse ratios of both GABAA and GABAB receptor-mediated IPSC components (IPSC2/IPSC1), suggesting an increase in presynaptic release of GABA. Consistent with increased gene dose, the level of the Kir3.2 subunit of potassium channels, effectors for postsynaptic GABAB receptors, was increased. This change was associated with enhanced postsynaptic GABAB/Kir3.2 signaling following application of the GABAB receptor agonist baclofen. Thus, both GABAA and GABAB receptor-mediated synaptic efficiency is increased in the Ts65Dn DG, thus likely contributing to deficient synaptic plasticity and poor learning in DS. PMID- 22062772 TI - Synaptic dysfunction in progranulin-deficient mice. AB - Progranulin haploinsufficiency is a common cause of familial frontotemporal dementia (FTD), but the role of progranulin in the brain is poorly understood. To investigate the role of murine progranulin (Grn) in the CNS in vivo, we generated mice targeted at the progranulin locus (Grn) using a gene-trap vector. Constitutive progranulin knockout mice (GrnKO) show moderate abnormalities in anxiety-related behaviors, social interactions, motor coordination, and novel object recognition at 8months of age, many of which differ between males and females. Analysis of synaptic transmission in 10-12 month old GrnKO male mice indicates altered synaptic connectivity and impaired synaptic plasticity. Additionally, apical dendrites in pyramidal cells in the CA1 region of the hippocampus in GrnKO males display an altered morphology and have significantly decreased spine density compared to wild-type (WT) mice. The observed changes in behavior, synaptic transmission, and neuronal morphology in GrnKO mice occur prior to neuropathological abnormalities, most of which are apparent at 18 but not at 8 months of age. We conclude that progranulin deficiency leads to reduced synaptic connectivity and impaired plasticity, which may contribute to FTD pathology in human patients. PMID- 22062773 TI - CD8-positive primary cutaneous peripheral T-cell lymphoma, unspecified. PMID- 22062774 TI - Informed consent for cataract surgery: patient understanding of verbal, written, and videotaped information. AB - PURPOSE: To determine the effectiveness of verbal, written, and videotaped descriptions of cataract surgery on patients' understanding of the risks, benefits, and treatment alternatives. SETTING: Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA. DESIGN: Randomized prospective study. METHODS: Patients eligible for cataract surgery were randomized into 1 of 4 arms of the informed consent process as follows: Group 1, conventional verbal information; Group 2, conventional verbal information plus second-grade reading level brochure; Group 3, conventional verbal information plus eighth-grade reading level brochure; Group 4, conventional verbal information plus American Academy of Ophthalmology DVD Understanding Cataract Surgery: Patient Education DVD Featuring an Aid to Informed Consent. After the informed consent process, patients in each group completed a 12-question questionnaire discussing the surgical procedure, its benefits, its foreseeable and unforeseeable risks, and the alternatives to cataract surgery. Scores in each group were calculated as the number of correct responses out of 12 questions. RESULTS: Patients in Group 2 (mean score 10.8 +/- 1.29 [SD]) and Group 4 (mean score 10.56 +/- 1.44) scored significantly higher than patients in Group 1 (mean score 7.68 +/- 2.80) or Group 3 (mean score 9.08 +/- 1.60). Previous cataract surgery and education level had no significant influence on recall of the informed-consent process. CONCLUSIONS: Concise informed consent information sheets at lower reading grade levels and videotape presentation optimized patient understanding of the risks, benefits, and treatment alternatives to cataract surgery. The cost-benefit of these results is important because better patient understanding has the potential to decrease the risk for indemnity payments awarded because of inadequate informed consent. PMID- 22062775 TI - Triplets, radical cations and neutral semiquinone radicals of lumiflavin and riboflavin: an overhaul of previous pump-probe data and new multichannel absolute absorption spectra. AB - Though long-lived transient photoproducts of flavins have received much attention over the last five decades, their spectroscopic characterization remains rudimentary and altogether inconclusive. Lumiflavin and riboflavin have therefore been reexamined, using nanosecond laser photolysis and multichannel detection over a wide spectral range (230-900 nm); differential absorption spectra of flavin solutions in aqueous buffer at neutral pH have been recorded; radical cations and semiquinone radicals were generated by quenching the triplets with C (NO(2))(4) (electron acceptor) and NO(2)(-) (electron donor), respectively. The problem of estimating the extent of ground state depletion after a single flash has been solved by developing a new strategy that provides reliable lower and upper bounds for the depletion (and for the molar absorption coefficients of the transient species of interest). The spectra of the neutral radicals and triplets of the two flavins are almost identical, but those of the two cations are not. PMID- 22062776 TI - Far infrared ray irradiation attenuates apoptosis and cell death of cultured keratinocytes stressed by dehydration. AB - Far infrared (FIR) irradiation has been widely applied in health promotion. The aims of this study were to investigate the protective effect of FIR irradiation on stressed keratinocytes and the signaling pathways involved. HaCaT was subjected to sorbitol dehydration with or without 40min pretreatment with FIR radiation 4h earlier. Western blots of cell lysates were analyzed for caspase-3, HO-1, BCL2, Bax, ERK, and Akt. The incidence of apoptosis was also assessed by TUNEL staining. Evaluation of cell viability was determined using MTT. mRNAs were extracted and compared using Illumina Human Ref-8 v2 BeadChips. Hyperosomotic injury of HaCaT cells caused by sorbitol resulted in increased cleaved caspase-3 expression and this effect was decreased by FIR pretreatment; these findings were confirmed by TUNEL staining and MTT tests. Pre-treatment with FIR irradiation before sorbitol-induced dehydration significantly upregulated phosphorylated Akt (p-Akt) levels and A6730, an Akt kinase inhibitor (5MUM), attenuated the protective effect of FIR irradiation. A microarray study showed FIR irradiation had far less effect at the transcriptional level. FIR pretreatment attenuates apoptosis and cell death in dehydration-stressed cultured keratinocytes through the PI-3K/Akt pathway, this protective effect of FIR irradiation is not at the transcriptional level. PMID- 22062777 TI - Quality properties of sausage made with gamma-irradiated natural pork and lamb casing. AB - Quality properties in emulsion-type sausage stuffed into irradiated natural casing were studied. Fresh salted and semidried natural pork and lamb casing was washed and irradiated at 0, 3, and 5 kGy by gamma-ray and emulsion-type pork sausage (Brattella Weiss Wurst) was manufactured. The sausage was stored in a 4 degrees C refrigerator. The numbers of total aerobic bacteria, Enterococcus and coliform bacteria in the irradiated natural casing or sausage prepared from irradiated casing were significantly decreased or eliminated compared to those of the nonirradiated control. The D(10) values of total aerobic bacteria of the pork and lamb casing were 0.87 and 0.92 kGy, respectively. The vacuum-packaged sausages made with irradiated casings had a higher 2-thiobarbituric acid reactive substances value than that of the nonirradiated controls only at 5-day with pork casing and at 10-day with lamb casing. The total working force for shear of the sausages was decreased in both irradiated casings but the sensory evaluation showed no difference. Therefore, the gamma irradiation was a useful technique to sanitize the natural pork and lamb casings and to extend shelf-life, primarily microbial quality, of the sausage made with natural casings. PMID- 22062778 TI - Sensory and chemical analysis of cooked porcine meat patties in relation to warmed-over flavour and pre-slaughter stress. AB - Two independent sensory profiles were carried out to evaluate warmed-over flavour (WOF) development in cooked, chill-stored and reheated pork patties. The patties were derived from the Musculus semimembranosus of animals subjected to different pre-slaughter stress treatments. All patties were stored in oxygen permeable bags at 4 degrees C for 0, 1, 2, 3 and 5 days to facilitate WOF development. In addition, thiobarbituric acid reactive substances (TBARS), conjugated dienes, pH, water content, total lipids and the fatty acid compositions of phosphatidyl choline (PC), phosphatidyl ethanolamine (PE) and total lipids, were measured in the cooked meat patties. A data analytical strategy involving Analysis of Variance-Partial Least Squares Regression (ANOVA-PLSR), to determine relationships between the design variables (WOF and pre-slaughter stress) and the sensory-chemical data, and PLSR to elucidate predictive links between the sensory and chemical data was utilised. WOF was found to involve the development of lipid oxidation derived nuance off-flavour and odour notes, e.g. rancid-like flavour and linseed oil-like odour, in association with a concurrent decrease in cooked pork meat-like flavour. The reduction in "meatiness", over the initial days, 0-2 of WOF development was attributed to the degradation of both, unstable sulfur containing amino acids in meat proteins and sulfur-containing "meaty" aroma compounds. Whereas, at the later days, 3-5 of WOF development the "meaty" loss was ascribed to perceptual masking by lipid oxidation products. TBARS and conjugated dienes were found to be significant (P<0.05) predictors of the sensory terms related to the lipid oxidation aspect of WOF. Whilst the polyunsaturated fatty acid (PUFAs) contents of PE, PC and the total lipids were found to decrease with WOF development, reflecting their loss in lipid oxidation reactions. The sensory variation related to pre-slaughter stress appeared to be distinct from WOF variation and was described by a sour to sweet taste continuum. However, interactions were noted that indicated increasing pre-slaughter stress resulted in a decreased sensory perception of WOF. Moreover, pH and water content were found to significantly (P<0.05) predict the sensory effects resulting from pre slaughter stress. PMID- 22062779 TI - Effect of replacing pork backfat with pre-emulsified olive oil on lipid fraction and sensory quality of Chorizo de Pamplona - a traditional Spanish fermented sausage. AB - Six treatments of Chorizo de Pamplona, traditional Spanish fermented sausage, were manufactured under usual commercial conditions by replacing 0, 10, 15, 20, 25 and 30% of pork backfat by pre-emulsified olive oil with soy protein isolate. Sausages with 20-30% replacing level had higher (P<0.05) protein content than control as a result of the addition of soy protein isolate. The oleic acid increased (P<0.05) in sausages with 15-30% replacing level, and linoleic acid increased in sausages with 10-25%. Sausages with 10-25% of substitution had lower total SFA-stearic and higher (P<0.05) total MUFA, total PUFA, (MUFA+PUFA)/(SFA stearic), and PUFA/(SFA-stearic). Cholesterol content showed reduction about 12 13% in sausages with 20-25% replacing level, and up to 22% in sausages with 30% replacing level. Sausages with 10-25% of substitution were acceptable from the sensorial point of view. The texture and colour instrumental measures were comparable with that of commercial products. No increments in hexanal content were observed. It is concluded that up to 25% of pork backfat can be replaced with pre-emulsified olive oil in the production of Chorizo de Pamplona fermented sausages. Higher replacing levels of pork backfat did not show nutritional advantages in relation to the fatty acid profile and were unacceptable due to considerable dripping of fat during ripening. PMID- 22062780 TI - Meat cut and injection level affects the tenderness and cook yield of processed roast beef. AB - The effect of muscle cut used and brine injection level on the processing characteristics of small pre-cooked roast beef was determined. Meat cuts (inside, outside, eye of round, knuckle, clod, chuck roll and brisket) were cut into small roasts (750 g) and injected at three levels (110, 125 and 150% over raw roast weight) with a non-injected control. Muscle cuts from the chuck can be used to successfully manufacture cooked mini roast beef. However, the use of small roasts resulted in cook yields that are considerably less than what was expected with large intact muscle roasts. Some variation in tenderness between the muscles was seen, but when muscles were injected there was a significant increase in tenderness and a reduction in the variability in tenderness within the muscle. Roasts injected to 125% above green weight resulted in the highest cook yields. PMID- 22062781 TI - Effect of starter culture and storage temperature on the content of biogenic amines in dry fermented sausage polican. AB - Water activity, pH, microbial counts (total counts/TCM/, coliforms, Enterobacter, Proteus, Pseudomonas, Escherichia and Lactobacillus spp., respectively), and seven biogenic amines (BA) were determined in dry fermented sausage 'polican' produced using starter culture A (Lactobacillus sakei, Staphylococcus carnosus, S. xylosus) or B (L. sakei, S. carnosus, Pediococcus pentosaceus), ripened 42 days, and subsequently stored at 8 or 22 degrees C 60 days. Counts of lactobacilli were higher and TCM lower in the A-sausage when ripening was finished. Tyramine (quantitatively most important BA) content was not different (P>0.05) in A- (90 mg/kg of dry matter, DM) or B-sausage (91 mg/kg DM) at the end of ripening. The effect of the storage temperature on BA content was not significant (P>0.05) in the case of either tyramine or any other tested BA. The increase of total BA content during ripening was not different (P>0.05) between A and B-sausages (final value 190 and 222 mg/kg DM, respectively). However, sum of BA was significantly higher (P<0.05) in B-sausage as compared with A-sausage at the end of either refrigerated storage (304 and 236 mg/kg DM) or room temperature storage (468 and 206 mg/kg DM, respectively). It is concluded that legislative limits should be established for tyramine and total BA content in dry fermented meat products. PMID- 22062782 TI - Meat quality of mixed sex lambs grazing pasture and supplemented with, roughage, oats or oats and sunflower meal. AB - The meat quality of 8-9-month-old cryptorchid, wether and ewe lambs (Poll Dorset*Border Leicester*Merino) was assessed. These lambs were grazed over summer and autumn from weaning (November) on lucerne (Medicago sativa) or ryegrass/clover (Lolium rigidum/trifolium subterranean) pasture at two locations (A or B). After 72 days lambs grazed on lucerne were supplemented with either ad lib clover hay or clover silage. Those grazed on the ryegrass/clover pasture were supplemented from weaning with either oat grain (400-600 g/h day and clover hay ad lib) or oat grain (200-400 g/h day) plus sunflower seed meal (200 g/h day) and clover hay ad lib. Lambs were slaughtered in April and May after they reached 48 kg liveweight. Lambs supplemented solely with roughage produced muscle (m. longissimus thoracis et lumborum; LTL) with a higher (P<0.05) pH, but there was no effect of nutrition or sex on meat colour or tenderness. Slaughter day affected tenderness of the topside (m. semimembranosus). Assessment of aroma, flavour and acceptability was undertaken on the m. biceps femoris from wether and cryptorchid lambs using an experienced taste panel. There was no clear effect of sex or nutrition on the assessment of the sensory attributes. However, panellists considered meat from cryptorchid lambs fed the oats/sunflower supplement and grazed at location B, to have a stronger aroma and flavour (P<0.05) and in some cases to be less acceptable than meat from other combinations of sex, diet and location. The most acceptable meat came from lambs supplemented with oats, irrespective of sex or location. As such, these effects could not be attributed solely to either the diet or sex, but suggest there are conditions where meat from cryptorchids can be less acceptable. PMID- 22062783 TI - Skatole and indole concentrations in Longissimus dorsi and fat samples of pigs. AB - A HPLC-NP (normal phase-high performance liquid chromatography) method for determining the concentration of skatole and indole in Longissimus dorsi samples is described. Lipids containing skatole and indole were extracted in chloroform:methanol (2:1) at room temperature and dehydrated by liquid-liquid extraction with an aqueous solution saturated with 10% of sodium chloride. The organic phase was evaporated to dryness and redissolved in 10 ml of hexane:2 propanol (92:8). Indolic compounds were separated on a Hypersil aminopropylsilica column (5 MUm) (250*4.6 mm i.d.). The mobile phase was hexane:2-propanol (92:8) and detection was by fluorescence (excitation at 280 nm and emission at 360 nm). Linearity was found in the range of 0.05-0.4 MUg/g and the coefficient of correlation was above 0.99 for both compounds. The within day (n=5) variation was at 0.05, 0.2 and 0.4 MUg/g and the CV (coefficient of variation) values for relative areas determined at these concentrations were less than 13%. This method was used to compare the concentrations of skatole and indole in different samples: L. dorsi muscle, the fat covering the L. dorsi and subcutaneous fat. A correlation was observed between the concentration of indole and skatole in the back fat and fat covering the L. dorsi samples (P<0.001, r=0.99). No significant correlation was obtained in L. dorsi samples, between skatole and indole levels. In spite of the correlation shown between skatole and indole concentrations in the back fat and L. dorsi samples, the mean concentrations of these compounds were significantly higher (P<0.05) in the back fat samples. PMID- 22062784 TI - The effect of ultra-rapid chilling and subsequent ageing on the calpain/calpastatin system and myofibrillar degradation in lamb M. longissimus thoracis et lumborum. AB - The effect of ultra-rapid chilling (-20 degrees C) on the proteolytic degradation of myofibrillar proteins during ageing, by the calpain/calpastatin system in lamb was investigated. Carcasses (36) were ultra-rapidly chilled (-20 degrees C for 3.5 h followed by 20.5 h at +4 degrees C) or chilling at +4 degrees C for 24 h. After chilling all carcasses were stored at +4 degrees C for a further 4 days. Samples of M. longissimus thoracis et lumborum were taken for Warner-Bratzler shear force measurement, sarcomere length, SDS-PAGE and enzyme activity analysis. Ultra-rapid chilling (-20 degrees C) had no effect on the proteolytic degradation of myofibrillar proteins by the calpain/calpastatin system compared to conventional chilling (+4 degrees C). However, no difference in tenderness was found between the two chilling regimes at 1 or 5 days postmortem so differences in myofibrillar degradation or enzyme activity would not be expected. PMID- 22062785 TI - Impact of introducing specifications on the tenderness of retail meat. AB - Over a 3-year period (1997-1999), the shear force of 4371 retail beef, lamb and pork midloin samples collected from 363 retail outlets were tested using a MIRINZ tenderometer. Information about aging time, processor and retail chain was recorded. Consumers (n=2313) were also surveyed on their perception of the tenderness of beef and lamb midloin samples with known shear force. The results validated that shear force, as measured by the MIRINZ tenderometer, could be used to create instrumental tenderness categories which reflected consumer perceptions of tenderness. Over the 3-year sampling period, the shear force of beef and lamb decreased by 21.9 and 17.2%, respectively, and there was a consistent decrease in the number of 'tough' samples. The improvement in tenderness coincided with the introduction of a Quality Mark program in 1997 for beef and lamb and 3 years of implementation by auditing. The Quality Mark program sets specifications for the quality of retail meat in New Zealand and guidelines to achieve these specifications. In comparison to retail beef and lamb, the shear force of retail pork decreased marginally by 7.9%. Furthermore, the decrease in the number of 'tough' pork samples was not consistent over the testing period. Analysis of these data showed that for all three meats a considerable improvement in tenderness can be achieved by adopting a minimum post-slaughter aging time and optimizing the processing conditions. PMID- 22062786 TI - Evaluation of carbon monoxide treatment in modified atmosphere packaging or vacuum packaging to increase color stability of fresh beef. AB - Our goal was to obtain > 21 days red color stability for carbon monoxide (CO) treated beef steaks in vacuum packaging (VP). In preliminary tests, pretreatment for 24 h in a 5% CO modified atmosphere package (MAP) was needed to maintain redness after re-packaging in VP. Pressure pretreatment with 5% CO for 2 h developed redness, but was impractical for large-scale application. Color stability and microbial load were then compared after treatment of steaks in 5% CO-MAP for 24 h, then VP; 100% CO-MAP for 1 h, then VP; steaks and ground beef in 0.5% CO-MAP; and steaks and ground beef in polyvinyl chloride (PVC) wrap. Steaks remained red for 5, 6, 8 and <1-week storage at 2 degrees C, respectively. Steaks microbial load exceeded spoilage levels (>10(6)cfu/cm(2)) at 5, 6, 7 and <2 weeks, respectively. Thus, extended color stability in VP was achieved by pretreatment with 5% CO for 24 h or 100% CO for 1 h. PMID- 22062787 TI - Fatty acid composition of adipose depots of suckling lambs raised under different production systems. AB - Forty-nine male Talaverana-breed suckling lambs slaughtered at 14 kg live weight were used to study the fatty acid composition of adipose depots of lambs raised under different management systems (pasture or drylot) and diets (maternal milk with or without a concentrate supplement). Drylot lambs displayed a higher fatness score, in addition to greater dorsal fat thickness; these parameters corresponded with a greater percentage of total fat at dissection. Addition of concentrate to the diet did not modify carcass fatness. Drylot lambs presented higher proportions of oleic acid (C18:1) and monounsaturated fatty acids (MUFA) and lower linolenic acid (C18:3) values in subcutaneous and intramuscular fat (muscle longissimus thoracis). The subcutaneous fat of these lambs thus displayed a higher n-6/n-3 PUFA ratio (C18:2/C18:3) than that of pasture-raised ones. Concentrate in the diet of both pasture and drylot lambs resulted in higher linoleic fatty acid (C18:2) and PUFA values and a greater PUFA/SFA ratio in intramuscular fat than the corresponding values of lambs which consumed maternal milk alone. Loin displayed a higher percentage of subcutaneous and intramuscular chemical fat than leg. Compared with intramuscular leg fat (muscle quadriceps femoris), intramuscular loin fat (muscle longissimus thoracis) had lower oleic acid (C18:1) and MUFA values, higher PUFA values and a higher PUFA/SFA ratio, due to greater linolenic acid (C18:3) levels. PMID- 22062788 TI - Comparison of meat quality characteristics between young and old ostriches. AB - Comparison of CIELAB colour values of the m. iliofibularis derived from 14 month old and 8 year old ostriches have indicated that an increase in age is accompanied with a significant (P<0.001) reduction in reflectance (L*) and a signiffcant increase in both a* (P<0.001) and b* (P<0.05) values, the meat thus becoming darker and redder with increased age. Comparison with results found in scientific literature suggest that, similar to other species, toughness also increases with age. Warner Bratzler values of the older ostriches were also higher than published results of 14 month old birds (4.44 kg/1.27 cm dia vs. 5.26 kg/1.27 cm dia). Intramuscular fatty acid composition and content of the older ostriches did not suggest any large variations compared with published results for younger (14 month old) ostriches. PMID- 22062790 TI - From the Editor's Perspective.... Suggestions to regain a healthy work-life balance. PMID- 22062791 TI - Portal vein aneurysm: a rare occurrence. AB - Portal vein aneurysms (PVA) are a rare vascular anomaly of the portal system, representing fewer than 3% of all venous aneurysms, with only 150 known cases since first reported in l956 by Barzilai and Kleckner. PVA can be divided into 2 categories: extrahepatic and intrahepatic with acquired and congenital etiologies. Bimodal treatment includes medical and surgical approaches. With increased use of noninvasive radiological imaging, PVA will be increasingly recognized in the practice of vascular surgery. PMID- 22062792 TI - Misdiagnosing aortic dissection: a fatal mistake. AB - Acute aortic dissection is one of the most fatal cardiovascular disorders that can challenge the most experienced practitioner. Despite recent progress in diagnostic tools, this vascular catastrophe is often misdiagnosed or undetected which can result in a 1%-3% mortality risk per hour. Many patients die before presenting to the hospital or prior to diagnosis. Therefore, a high index of clinical suspicion is critical to reach the correct diagnosis, if proper management is to be achieved. Clinical predictors for aortic dissection include abrupt chest pain or back pain, pulse and blood pressure differentials, and a radiographic widening of the mediastinum. A clear understanding of the pathophysiology and risk factors associated with aortic dissection is the cornerstone of prompt diagnosis and treatment. This paper will provide an overview of the etiology, pathology, clinical presentation, diagnosis and treatment of this condition. PMID- 22062793 TI - Peripheral arterial disease: application of the chronic care model. AB - Management of chronic diseases is one of the greatest challenges facing health care professionals globally. With the aging population increasing worldwide, the number of patients afflicted with chronic diseases will increase. Peripheral Arterial Disease (PAD) is a common, chronic atherosclerotic vascular disease that is associated with a high risk of stroke, myocardial infarction and cardiovascular death. The objective of this study was to determine if a multidisciplinary Vascular Risk Management Clinic (VRMC) would improve risk factor management and health outcomes for patients with PAD with poorly controlled risk factors. A multidisciplinary VRMC was established utilizing a novel application of the Chronic Care Model to meet the needs of PAD patients. Interventions included optimization of medical therapy, investigations for undiagnosed atherosclerosis in other vascular distributions, smoking cessation therapy, dietary assessment and counseling, and active involvement of patients in evaluating progress towards their risk factor target goals. Assessment of risk factor control was done at each clinic visit and included measures of symptom severity, blood pressure, fasting blood sugar (FBS), lipid profile, body mass index (BMI), and smoking status. Analysis of risk factors was performed for the first 103 patients followed in the clinic. Average follow-up time was 528 days, and statistically significant improvements were seen in blood pressure, LDL, HDL, total cholesterol (TC), and TC/HDL ratio, while BMI, FBS, and triglycerides remained stable. Participation in a specialized vascular risk management clinic resulted in significant improvement in risk factors for disease progression compared to baseline status. PMID- 22062794 TI - Got PAD? Hidden dangers revealed with ABI. AB - Peripheral artery disease (PAD), a result of atherosclerotic vascular changes to the endothelial lining of blood vessels, affects 8-12 million Americans and increases the risk of mortality as much as 50% from heart attacks and strokes. Early diagnosis and treatment of PAD along with early risk-reduction strategies have the potential to decrease societal health costs, as well as morbidity and mortality. PAD through screening with ankle brachial index (ABI), versus relying on existing physical exam and screening questionnaires, can increase the number of participants correctly diagnosed with PAD and lead to earlier treatment options. ABI screening was implemented in a primary care practice setting; outcomes were compared with historical rates and outcomes for participants at risk who declined ABI. Authors concluded that the participants who had ABI screenings that included arterial waveform analysis had a 78% rate of PAD diagnosis, whereas only 13% of the participants who did not elect ABI screening were diagnosed with PAD based on their symptoms and physical exam. Use of ABI screening led to increased frequency and awareness of PAD diagnosis and the opportunity for early intervention. PMID- 22062795 TI - Prevalence, characteristics, and predictors of pulmonary vein narrowing after isolation using the pulmonary vein ablation catheter. AB - BACKGROUND: The risk of pulmonary vein narrowing (PVN) after pulmonary vein isolation, using a novel multi-electrode ablation catheter, is unknown. METHODS AND RESULTS: Left atrial volume and PV diameters were compared by computed tomography (CT) before and 3 months after pulmonary vein isolation using duty cycled phased radio frequency energy (2:1 or 4:1 bipolar/unipolar ratio) in 50 patients. Pulmonary vein diameter was measured in a coronal and axial view at 3 levels (A, ostium; B, 1 cm more distal; C, 2 cm more distal). Moderate PVN was defined as a pulmonary vein diameter reduction of 25 to 50%, and severe PVN as >50%. Left atrial volume decreased by 12+/-12% (P<0.01). Axial pulmonary vein diameter shortened by a median of 16% (interquartile range [IQR] 28 to 5%), 13% (IQR 25 to 5%), and 9% (IQR 21 to -3%) at level A, B, and C, respectively (P<0.01 for all); coronal pulmonary vein diameter decreased by a median of 16% (IQR 24 to 7%), 11% (IQR 21 to 4%), and 8% (IQR 18 to -2%; P<0.01 for all). Moderate PVN occurred in 30% of the PVs, in 78% of the patients; severe PVN occurred in 4% of the PVs, in 15% of the patients. PV diameter reduction was not related to changes in left atrial volume. CONCLUSIONS: Isolation of the pulmonary veins using a multielectrode ablation catheter and duty cycled phased radiofrequency energy delivery results in a consistent moderate reduction of the PV diameters predominantly at the ostium. Severe PVN in 15% of patients raises concerns about the risk for clinical PV stenosis. PMID- 22062796 TI - Endocardial left ventricular pacing improves cardiac resynchronization therapy in chronic asynchronous infarction and heart failure models. AB - BACKGROUND: Studies in canine hearts with acute left bundle branch block (LBBB) showed that endocardial left ventricular (LV) pacing improves the efficacy of cardiac resynchronization therapy (CRT) compared with conventional epicardial LV pacing. The present study explores the efficacy of endocardial CRT in more compromised hearts and the mechanisms of such beneficial effects. METHODS AND RESULTS: Measurements were performed in 22 dogs, 9 with acute LBBB, 7 with chronic LBBB combined with infarction (embolization; LBBB plus myocardial infarction, and concentric remodeling), and 6 with chronic LBBB and heart failure (rapid pacing, LBBB+HF, and eccentric remodeling). A head-to-head comparison was performed of the effects of endocardial and epicardial LV pacing at 8 sites. LV activation times were measured using ~100 endocardial and epicardial electrodes and noncontact mapping. Pump function was assessed from right ventricular and LV pressures. Endocardial CRT resulted in better electric resynchronization than epicardial CRT in all models, although the benefit was larger in concentrically remodeled LBBB plus myocardial infarction than in eccentrically remodeled LBBB+HF hearts (19% versus 10%). In LBBB and LBBB+HF animals, endocardial conduction was ~50% faster than epicardial conduction; in all models, transmural impulse conduction was ~25% faster when pacing from the endocardium than from the epicardium. Hemodynamic effects were congruent with electric effects. CONCLUSIONS: Endocardial CRT improves electric synchrony of activation and LV pump function compared with conventional epicardial CRT in compromised canine LBBB hearts. This benefit can be explained by a shorter path length along the endocardium and by faster circumferential and transmural impulse conduction during endocardial LV pacing. PMID- 22062797 TI - Remote-controlled magnetic navigation and ablation with 3D image integration as an alternative approach in patients with intra-atrial baffle anatomy. AB - BACKGROUND: Improvement in outcome of infants born with congenital heart defects has been accompanied by an increasing frequency of late arrhythmias. Ablation is difficult because of multiple tachycardias in the presence of complex anatomy with limited accessibility. We report on remote-controlled ablation using magnetic navigation in conjunction with 3D image integration in patients with previous intra-atrial baffle procedures. METHODS AND RESULTS: Thirteen patients (8 male; age, 30.5+/-8 years) with supraventricular tachycardia (SVT) underwent catheter ablation. Group A had a medical history of a Mustard or Senning operation, whereas group B had undergone total cavopulmonary connection. A total of 26 tachycardias were treated in 17 procedures (median cycle length of 280 ms). Group A patients had more inducible SVTs than group B, and all index SVTs were located in the remainder of the morphological right atrium in all but 1 patient. Retrograde access through the aorta was performed and led to successful ablation, using magnetic navigation with a very low total radiation exposure (median of 3.8 minutes in group A versus 5.9 minutes in group B). Only 1 of 13 patients continued to have short-lasting SVTs despite 3 ablation procedures during a median follow-up time of >200 days. CONCLUSIONS: Remote-controlled catheter ablation by magnetic navigation in combination with accurate 3D image integration allowed safe and successful elimination of SVTs, using an exclusively retrograde approach, resulting in low radiation exposure for patients after intra-atrial baffle procedures (Mustard, Senning, or total cavopulmonary connection). PMID- 22062798 TI - Effect of culture density and antioxidants on naupliar production and gene expression of the cyclopoid copepod, Paracyclopina nana. AB - Although attempts have been made to use mass cultures of marine copepods as live foods in marine aquaculture, some limitations such as low density culture still exist. The brackish water cyclopoid copepod, Paracyclopina nana has the potential for mass culturing as live food. In this study, we not only investigated the effect of culture density on the naupliar production and specific gene expressions of P. nana, but also the effect of several antioxidants under the conditions of a high density culture. The naupliar production of the copepod decreased with increasing culture density. The expression of glutathione reductase (GR), selenium-dependent glutathione peroxidase (SeGPx), glutathione S transferase kappa (GST kappa), heat shock protein 40 (Hsp40), and Hsp70 genes of P. nana increased in the high density treatment but vitellogenin genes (Vg1 and Vg2) showed downregulation. In the condition with 20 inds./mL, vitamin C had a significant decrease but sodium selenite induced the naupliar production of P. nana greatly. The expressions of GR, SeGPx, Hsp70, and Vg genes increased with the vitamin C treatment. Sodium selenite caused a decrease of SeGPx and Hsp40 but GST kappa increased in the treatment with 20 inds./mL. These results suggest that sodium selenite is a positive antioxidant which can increase the culture efficiency of the copepod. PMID- 22062799 TI - Effect of starvation and refeeding on digestive enzyme activities in juvenile roach, Rutilus rutilus caspicus. AB - We evaluated the effects of starvation and refeeding on digestive enzyme activities in juvenile roach, Rutilus rutilus caspicus. Fish were divided into four feeding groups (mean mass 1.68 +/- 0.12 g). The control group was fed to satiation twice a day throughout the experiment with formulated diet (SFK). The other three groups were deprived of feed for 1(S1), 2(S2), and 3(S3) weeks, respectively, and then fed to satiation during the refeeding period. The results showed that trypsin specific activity was not affected significantly either by starvation or refeeding, in all experimental groups. Chymotrypsin specific activity did not change significantly in S1 fish during the experimental period. In S2 and S3 fish no significant changes were observed during the starvation period. Upon refeeding, the activity increased in S2 fish, while it decreased in S3 fish. Amylase specific activity decreased significantly during the starvation period in all experimental groups. Upon refeeding, the activity increased. Alkaline phosphatase specific activity did not change significantly during the experiment period in S3 fish, while it showed significant changes during the starvation and refeeding period in the S1 and S2 fish. Starvation also had a significant effect on the structure of the intestine. PMID- 22062800 TI - The physiological ecology of the supratidal amphipod Talorchestia longicornis. AB - Physiology, behavior, habitat, and morphology are used to determine the degree of adaptation to life on land for amphipod species and systemization within the four functional groups of the family talitridae. Talorchestia longicornis is a semi terrestrial amphipod found in the supratidal zone of estuaries. The present study investigates the physiological adaptations of this species to life on land through measurements of osmoregulation and respiration. Over the salinity range of 1-400/00, T. longicornis regulated its hemolymph hyperosmotically at low salinities and hypoosmotically at high salinities. The isosmotic point was about 270/00. Analogously, hemolymph chloride levels were well regulated being hyperionic at low salinities and hypoionic at high salinities. This species is capable of respiration in both air and water. Slopes (b values) of the relationship between weight and oxygen uptake rates ranged from 0.316 to 0.590. Oxygen uptake rates were higher in air than water and at night versus day. Q(10) values were slightly below 2.0 for respiration in air for amphipods, irrespective of weight. These physiological adaptations, along with its behaviors, habitat, and morphology, place T. longicornis within the Group III sandhoppers of the Talitridae. PMID- 22062801 TI - Relationship of race/ethnicity and survival after single umbilical cord blood transplantation for adults and children with leukemia and myelodysplastic syndromes. AB - The relationship of race/ethnicity with outcomes of umbilical cord blood transplantation (UCBT) is not well known. We analyzed the association between race/ethnicity and outcomes of unrelated single UCBT for leukemia and myelodysplastic syndromes. Our retrospective cohort study consisted of 885 adults and children (612 whites, 145 blacks, and 128 Hispanics) who received unrelated single UCBT for leukemia and myelodysplastic syndromes between 1995 and 2006 and were reported to the Center for International Blood and Marrow Transplant Research. A 5-6/6 HLA-matched unit with a total nucleated cell count infused of >=2.5 * 10(7)/kg was given to 40% white and 42% Hispanic, but only 21% black patients. Overall survival at 2 years was 44% for whites, 34% for blacks, and 46% for Hispanics (P = .008). In multivariate analysis adjusting for patient, disease, and treatment factors (including HLA match and cell dose), blacks had inferior overall survival (relative risk of death, 1.31; P = .02), whereas overall survival of Hispanics was similar (relative risk, 1.03; P = .81) to that of whites. For all patients, younger age, early-stage disease, use of units with higher cell dose, and performance status >=80 were independent predictors of improved survival. Black patients and white patients infused with well-matched cords had comparable survival; similarly, black and white patients receiving units with adequate cell dose had similar survival. These results suggest that blacks have inferior survival to whites after single UCBT, but outcomes are improved when units with a higher cell dose are used. PMID- 22062802 TI - Risk factors for progression from cytomegalovirus viremia to cytomegalovirus disease after allogeneic hematopoietic stem cell transplantation. AB - Cytomegalovirus (CMV) disease is a major cause of infectious complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although patients undergoing allo-HSCT receive prophylactic and preemptive treatment for CMV, a subset of patients experience clinically significant CMV disease. This study investigated the risk factors for progression from CMV viremia to CMV disease during or after preemptive therapy in patients undergoing allo-HSCT. Between January 2006 and August 2010, 43 patients received preemptive therapy for CMV viremia after allo-HSCT. These patients experienced 74 episodes of CMV viremia. Nine of the patients (21%) and 12 of the episodes (16%) progressed to CMV disease. Univariate analysis identified several risk factors for progression to CMV disease, including high initial viral load (P = .020), leukopenia (P = .012), and neutropenia (P = .033) at the time of detection of CMV viremia. On multivariate analysis, leukopenia remained an independent predictor (hazard ratio, 4.347; P = .045). The rate of failure to clear CMV viremia after 1 cycle of preemptive therapy was higher in the leukopenia group than in the non leukopenia group (60.0% versus 16.9%; P = .002). This indicates that leukopenia initially documented with CMV viremia is related to lower viral response to preemptive therapy and is a notable risk factor for progression from CMV viremia to CMV disease. PMID- 22062803 TI - CD3+/Tregs ratio in donor grafts is linked to acute graft-versus-host disease and immunologic recovery after allogeneic peripheral blood stem cell transplantation. AB - Graft-versus-host disease (GVHD), mediated by mature T cells present in the donor graft, remains a major complication after allogeneic peripheral blood stem cell transplantation (PBSCT). Regulatory T cells (Tregs) (CD4(+)CD25(high)Foxp3(+)) are believed to maintain tolerance and to inhibit GVHD after allogeneic PBSCT (allo-PBSCT). In this study, we analyzed the graft CD3(+)/Tregs ratio (gCD3/Tregs R) and evaluated its impact on acute GVHD (aGVHD) and immunologic recovery after myeloablative allo-PBSCT. We analyzed 65 consecutive patients who underwent transplantation with unmanipulated peripheral blood stem cells from an HLA identical related donor (n = 45) or an HLA-identical unrelated donor (n = 20). The median CD3(+) and Tregs doses administered were 256 * 10(6)/kg of body weight (range, 67-550 * 10(6)/kg) and 12 * 10(6)/kg (range, 2-21 * 10(6)/kg), respectively; the median gCD3/Tregs R value was 18 (range, 8-250). Patients were subdivided into a high gCD3/Tregs R (>=36) group (HR; n = 26) and a low gCD3/Tregs R (<36) group (LR; n = 39). The incidence of aGVHD (grade II-IV) was lower in the LR group compared with the HR group (8/39 [20%] versus 22/26 [84%]; P < .001). Median cytomegalovirus-specific CD8(+) T lymphocytes were significantly higher in the LR group than in the HR group at 1 month (2 cells/MUL versus 0 cells/MUL; P < .001), 2 months (6 cells/MUL versus 1 cell/MUL; P < .001), and 3 months (15 cells/MUL versus 3 cells/MUL; P < .001) months. Moreover, cytomegalovirus infection/disease was observed in 15% of patients in the LR group versus 69% of patients in the HR group (P < .001). At multivariate logistic regression, gCD3/Tregs R was correlated both with aGVHD (odds ratio, 2.50; 95% confidence interval, 1.30-4.50; P = .05) and with cytomegalovirus infection/disease (odds ratio, 2.35; 95% confidence interval, 0.9-5.00; P = .05). Taken together, our data may suggest that the balance in favor of graft Tregs content is able to mediate protective effects against aGVHD and to maintain an optimal microenviroment for the reconstitution of functional immunity. PMID- 22062804 TI - Second autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on progression-free and overall survival. AB - The role of a second autologous stem cell transplant (ASCT) as salvage therapy is unclear, particularly with the availability of novel agents to treat progressive multiple myeloma (MM). We retrospectively reviewed all MM patients who received a second ASCT as salvage therapy at our center from March 1992 to December 2009. Eighty-one MM patients received a second ASCT for relapsed MM. The median time to relapse after first transplant was 39 months (9.83-100). All patients received reinduction therapy before the second ASCT. The high-dose regimen given before the second ASCT consisted of melphalan (MEL) alone in the majority. Complete response, very good partial response, and partial response were seen in 7.7%, 39.7%, and 50%, respectively, at day 100 post-ASCT; the median time to relapse after the second ASCT was 19 months. Early deaths occurred in 2.6%. Median progression-free survival (PFS) based on the time to myeloma relapse after first ASCT was 9.83 months (relapse <= 24 months) and 17.3 months (relapse >= 24 months) (P < .05). Median overall survival (OS) was 28.47 months (relapse <= 24 months) and 71.3 months (relapse >24 months) (P = .006). Second ASCT is a feasible and safe option for salvage therapy in MM. The best outcome was observed in patients whose time to progression was >24 months after first ASCT, as these patients had a subsequent PFS lasting over 1 year and an OS of almost 6 years. PMID- 22062805 TI - In situ detection of HY-specific T cells in acute graft-versus-host disease affected male skin after sex-mismatched stem cell transplantation. AB - HY-specific T cells are presumed to play a role in acute graft-versus-host disease (aGVHD) after female-to-male stem cell transplantation (SCT). However, infiltrates of these T cells in aGVHD-affected tissues have not yet been reported. We evaluated the application of HLA-A2/HY dextramers for the in situ detection of HY-specific T cells in cryopreserved skin biopsy specimens. We applied the HLA-A2/HY dextramers on cryopreserved skin biopsy specimens from seven male HLA-A2(+) pediatric patients who underwent stem cell transplantation with confirmed aGVHD involving the skin. The dextramers demonstrated the presence of HY-specific T cells. In skin biopsy specimens of three male recipients of female grafts, 68% to 78% of all skin-infiltrating CD8(+) T cells were HY specific, whereas these cells were absent in biopsy specimens collected from sex matched patient-donor pairs. Although this study involved a small and heterogeneous patient group, our results strongly support the hypothesis that HY specific T cells are actively involved in the pathophysiology of aGVHD after sex mismatched stem cell transplantation. PMID- 22062806 TI - Ginsenoside Rg2 induces orphan nuclear receptor SHP gene expression and inactivates GSK3beta via AMP-activated protein kinase to inhibit hepatic glucose production in HepG2 cells. AB - Panax ginseng is known to have anti-diabetic activity, but the active ingredients have not been fully explored yet. Here, we test whether ginsenoside Rg2 has an inhibitory effect on hepatic glucose production and determine its mechanism of action. Rg2 significantly inhibits hepatic glucose production and induces phosphorylations of liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK) and glycogen synthase kinase 3beta (GSK3beta) in time- and concentration dependent manners in human HepG2 hepatoma cells, and these effects were abolished in the presence of compound C, a selective AMPK inhibitor. In addition, phosphorylated form of cAMP-response element-binding protein (CREB), a key transcription factor for hepatic gluconeogenesis, was decreased in time- and concentration-dependent manners. Next, gene expression of orphan nuclear receptor small heterodimer partner (SHP) was also examined. Rg2 markedly enhanced the gene expression of SHP and its direct interaction with CREB, which results in disruption of CREB.CRTC2 complex. Consequently, expressions of relevant genes such as peroxisome proliferation-activated receptor gamma coactivator-1alpha (PGC 1alpha), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were all significantly suppressed and these effects were also reversed in the presence of compound C. In conclusion, our results propose that ginsenoside Rg2 suppresses the hepatic glucose production via AMPK-induced phosphorylation of GSK3beta and induction of SHP gene expression. Further studies are warranted to elucidate a therapeutic potential of Rg2 for type 2 diabetic patients. PMID- 22062807 TI - Occurrence and prevalence of seven bee viruses in Apis mellifera and Apis cerana apiaries in China. AB - Populations of Apis mellifera and Apis cerana in China were surveyed for seven bee viruses: acute bee paralysis virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV), deformed wing virus (DWV), Kashmir bee virus (KBV), sacbrood virus (SBV), and Isreal acute paralysis virus (IAPV). No KBV was detected from any samples of the two species. In A. mellifera, DWV was the most prevalent virus, but in A. cerana, SBV was the dominant. Simultaneous multiple infections of viruses were common in both species. This is the first report of detection of IAPV and CBPV in A. cerana. PMID- 22062808 TI - Non-destructive estimation of the intramuscular fat content of the longissimus muscle of pigs by means of spectral analysis of ultrasound echo signals. AB - The eating quality of porcine meat is supposed to increase with increasing intramuscular fat content (IMF). The aim of this study was to investigate the use of acoustic parameters obtained by spectral analysis of ultrasound echo signals to non-destructively predict intramuscular fat content of porcine longissimus muscle. Ultrasound is regarded as a promising non-destructive technique to characterize tissue. Ultrasound data acquisition was performed at slaughter with a clinical B-mode device equipped with a 3.5 MHz center-frequency transducer on 115 warm carcasses about 45 min postmortem. Acoustic parameters quantifying attenuation, backscattering and cepstral structure were calculated off-line from the recorded primary raw ultrasound echo signals. Their relationship to IMF content was investigated. IMF level significantly influenced powerspectrum amplitudes and backscatter parameters. With partial least-squares regression (PLS), the IMF content could be predicted with root mean standard error of prediction RMSEP of 0.36% IMF. The ultrasound parameters were able to correctly classify nearly 80% of the carcasses into HIGH and LOW level class, respectively. Results indicate the potential use of ultrasound spectral analysis for non destructive evaluation (NDE) of pig carcasses in order to estimate the IMF content. PMID- 22062809 TI - Post-salting studies in Spanish cured ham manufacturing. Time reduction by using brine thawing-salting. AB - The use of the simultaneous brine thawing/salting on frozen raw material was compared in a previous work with the traditional pile salting method. The aim of this study was to characterise and compare the post-salting stage in Spanish cured ham production by processing fresh and thawed raw material with the traditional pile salting method (which can be considered as the reference method), with the results obtained using the brine thawing/salting method, with and without applying vacuum impregnation. The obtained results show that the thawed salted hams exhibited a higher NaCl diffusion than the fresh ones, implying a shorter post-salting period. Post-salting stage could be reduced from the 50 days employed in the traditional fresh raw material salting, to 25 days when using frozen hams brine thawed/salted. No influence of the use of vacuum impregnation during the salting stage was observed on the post-salting period. PMID- 22062810 TI - Effect of trisodium phosphate on slip and textural properties of hog and sheep natural sausage casings. AB - The defective gliding of certain natural casings during the stuffing of sausages is an important problem in the meat processing industry. The gliding behaviour of (defective) hog and sheep casings was assessed with a newly developed instrument, and by a technologist during the stuffing of sausages. Casings were treated with 0.01 M trisodium phosphate; control casings were untreated. Cooked and smoked sausages were made in hog casings treated or untreated with phosphate and subjected to compression tests. In all cases the treatment with phosphate clearly facilitated the gliding of the casings over the test pipes, as compared to the control casings. The instrument to measure the casing gliding properties did not provide reliable information about the actual stuffing of sausages. The phosphate treated casings had a lower shear force than the control casings after being used as skins for cooked and smoked sausages. If confirmed, the finding that mild phosphate treatment can diminish the force required to shear a casing will be of interest to the sausage industry because the toughness of certain hog casings is considered a problem. PMID- 22062811 TI - The influence of biochemical differences on the variation in tenderness of M. longissimus dorsi of Belgian Blue steers managed homogenously pre and post slaughter. AB - The objective of this experiment was to determine the contribution of some biochemical processes of postmortem muscle to the variation in tenderness of beef from Belgian Blue bull cross Holstein-Friesian steers (n=10). These animals were managed optimally from conception to consumption with the aim of reducing tenderness variation. The M. longissimus dorsi (LD) from the left hand side (LHS) and the right hand side (RHS) were analysed for variation in tenderness using Bartletts test. The quality measurements included pH, temperature, Warner Bratzler shear force, sensory tenderness, chemical composition and sarcomere length. Biochemical measurements included myofibrilar proteolysis, glycolytic potential, adenine/inosine ratio and collagen content. No difference for variances or means were observed between LHS and RHS for chemical, quality or biochemical attributes. Biochemical variation was greater than the variation observed in most of the quality attributes measured. Proteolysis was the main biochemical contributor to the variation in shear force tenderness after 2 and 7 as postmortem, but not sensory tenderness. Glycolysis levels and adenine/inosine ratio explained much of the variation in sensory tenderness, but not WBSF. Collagen content in the LD muscles did not explain variation in shear force or sensory tenderness. This would suggest biochemical variation is one of the main contributors to variation in tenderness of beef managed optimally pre- and post slaughter. PMID- 22062812 TI - High hydrostatic pressure inactivation of vegetative microorganisms, aerobic and anaerobic spores in pork Marengo, a low acidic particulate food product. AB - To prolong the shelf-life of particulate food products, high pressure processing is one of the emerging technologies to be studied as an alternative to classical pasteurization and sterilization by heat. Pork Marengo (a low acidic, partially prepared stew of pieces pork, carrots and peas) was inoculated with several strains of sporulating and vegetative microorganisms. The microbial spoilage of the product was evaluated after a high pressure treatment of 400 MPa during 30 min at, respectively, 20 and 50 degrees C. Several Clostridium spp. and Bacillus spp. survived the treatment, and the Gram-positive cocci Enterococcus faecalis and Staphylococcus aureus were revealed to be more pressure resistant than Saccharomyces cerevisiae and the Gram-negative bacteria Pseudomonas fluorescens and Escherichia coli. The high pressure treatment at 20 degrees C demonstrated that high pressure processing (HPP) of neutral-pH foods cannot rely on pressure alone as a pasteurization/sterilization process. Another physical agent like heat is needed. High pressure treatment at 50 degrees C demonstrated that heat transfer limitations in particulate food products still can trouble their successful pasteurization/sterilization. PMID- 22062813 TI - Dietary manipulation of fatty acid composition in lamb meat and its effect on the volatile aroma compounds of grilled lamb. AB - The effect on lamb muscle of five dietary supplements high in polyunsaturated fatty acids (PUFA) was measured. The supplements were linseed oil, fish oil, protected lipid (high in linoleic acid (C18:2 n-6) and alpha-linolenic acid (C18:3 n-3)), fish oil/marine algae (1:1), and protected lipid/marine algae (1:1). Eicosapentaenoic acid (C20:5 n-3) and docosahexaenoic acid (C22:6 n-3) were found in the highest amounts in the meat from lambs fed diets containing algae. Meat from lambs fed protected lipid had the highest levels of C18:2 n-6 and C18:3 n-3, due to the effectiveness of the protection system. In grilled meat from these animals, volatile compounds derived from n-3 fatty acids were highest in the meat from the lambs fed the fish oil/algae diet, whereas compounds derived from n-6 fatty acids were highest in the meat from the lambs fed the protected lipid diet. PMID- 22062814 TI - On-line determination of fatty acid composition in intramuscular fat of Iberian pork loin by NIRs with a remote reflectance fibre optic probe. AB - A near infrared spectrometer equipped with a standard 210/210 bundle remote reflectance fibre-optic probe, with a 5*5 cm quartz window type, was used for the determination of fatty acids in the Longissimus dorsi muscle of Iberian breed swine. The fatty acids C14:0, C16:0, C16:1, C17:0, C17:1, C18:0, C18:1, C18:2, C18:3, Sigmapolyunsaturated, Sigmamonounsaturated and Sigmasaturated were determined in samples of intramuscular fat from Iberian breed swine by direct application of the fibre-optic probe onto the loin sample, with no treatment or manipulation of the sample. The regression method employed was modified partial least squares. The calibration results using the fibre-optic probe for 74 loin samples had multiple correlation coefficients (RSQ) for C14:0, C16:0, C16:1, C17:0, C17:1, C18:0, C18:1, C18:2, C18:3, Sigmapolyunsaturated, Sigmamonounsaturated and Sigmasaturated acid of 0.785, 0.798, 0.788, 0.825, 0.762, 0.765, 0.696, 0.859, 0.878, 0.807, 0.943, 0.858, respectively, and standard errors of prediction corrected for the same fatty acids (%) of 0.08, 0.63, 0.26, 0.02, 0.02, 0.51, 0,77, 0.64, 0.05, 1.06, 0.34, 0.70, respectively. The robustness of the method was checked by applying the fibre-optic probe to unknown samples of Iberian breed pork loin in a slaughterhouse, using 15 samples for the external validation. PMID- 22062815 TI - Texture parameters of dry-cured ham m. biceps femoris samples dried at different levels as a function of water activity and water content. AB - Instrumental texture parameters of m. biceps femoris (BF) samples from six commercial dry-cured hams, dried to a different degree, were related to water activity and water content. Samples were carved into cubes and Texture Profile Analysis (compression 50%, 10 mm high samples), water activity (a(w) 25 degrees C) and water content analyses were performed. A negative non-linear relationship between hardness and water content and water activity was observed. From this relationship, critical X and a(w) values, below which there is a dramatic increase in hardness, can be found (around 0.55 kg H(2)O/kg dry matter and around 0.70, respectively). Cohesiveness and springiness showed a positive linear relationship with water content and water activity. PMID- 22062816 TI - Prediction of the chemical composition of freeze dried ostrich meat with near infrared reflectance spectroscopy. AB - Near infrared reflectance spectroscopy (NIRS) was used to predict the chemical composition of freeze-dried ostrich meat samples. Tenderloin (M. ambiens), big drum (M. iliofibularis) and fan fillet (M. gastrocnemius) samples (n=160) were included in the study. Samples were minced, freeze-dried and analysed according to standard laboratory procedures for ash, dry matter (DM), crude protein (CP) and fat content. Samples were scanned (1100-2500 nm) and partial least-square regression (PLSR) was used to predict the chemical composition. Multiple correlation coefficients (r) and standard errors of calibration (SEC) for the chemical analysis of freeze-dried ostrich meat were: ash (0.72; 0.29%); DM (0.72; 1.01%); CP (0.98; 0.55%); and fat (0.99; 0.29%). The r values for the validation set and the standard error of performance (SEP) for the different constituents were: ash (0.71; 0.23%); DM (0.84; 0.72%); CP (0.97; 0.64%); and fat (0.99; 0.18%). Calibrations were accurate for CP and fat. PMID- 22062817 TI - An evaluation of selected methods for the decontamination of cattle hides prior to skinning. AB - The effectiveness of different decontamination treatments in reducing microbial loads on cattle hides was assessed. The 10-s hide treatments were conducted using a wet-and-dry vacuum cleaner filled with one of the liquids (heated to 50 degrees C) indicated below, followed or not by 10-min drying in the air. Also, the hide was clipped, followed or not by 10-s singeing using a hand-held blowtorch. Before and after each decontamination treatment, the hide was sampled (100 cm(2) areas) by a sponge-swabbing method to compare the total viable counts of bacteria (TVC). The largest bacterial reduction (P<0.001; 2.31log(10) cfu/cm(2)) was achieved by singeing of previously clipped hide. Treatment of hide with a food industry sanitizer solution (10% Betane Plus) resulted in significant reductions of 1.80 (P<0.001) and 1.98log(10) cfu/cm(2) (P<0.001) without and with subsequent drying, respectively. Treatment of hide with a food industry disinfectant (P3-Topactive DES) significantly reduced TVC by 0.97 (P<0.001) and 1.18log(10) cfu/cm(2) (P<0.001) without and with subsequent drying, respectively. Treatments of hide with water alone or with a food-safe detergent solution (Formula 963B), or hide clipping alone, did not produce significant decontamination effects. Since hide contamination is associated with microbial contamination of the carcasses, the results indicate that post-killing/pre skinning hide decontamination (used alone, or in combination with carcass decontamination) has a potential to improve microbial meat safety. Nevertheless, further research is required to optimise the efficacy of these treatments in the reduction of specific pathogens under commercial conditions. PMID- 22062818 TI - Effect of radiation processing on the quality of chilled meat products. AB - Effect of radiation processing on the shelf-life and safety of some ethnic Indian meat products like chicken chilly, mutton shammi kababs and pork salami during chilled storage was investigated. Radiation processing resulted in dose dependent reduction in microbial counts. A dose of 3 kGy was found to be optimal for the shelf-life extension. In all the three irradiated (3 kGy) meat products the shelf life was extended by more than 2 weeks at 0-3 degrees C compared to the corresponding non-irradiated samples. Staphylococcus spp. were completely eliminated by irradiation at a dose of 2 kGy. Some increase in lipid peroxidation on irradiation was observed as measured by TBA assay but it did not affect the sensory attributes of the product. PMID- 22062819 TI - Characteristics of impala (Aepyceros melampus) skeletal muscles. AB - The aim of this study was to determine citrate synthase (CS), phosphofructokinase (PFK) activities and myosin heavy chain (MHC) isoform contents in four muscle groups (semimembranosus (S), deltoideus (D), longissimus lumborum (LL), and psoas major (PM)) of impala (n=6). All four muscle groups expressed predominantly MHC IIa (means of 55+/-22-93+/-12%). MHC IIx was only expressed in D. In D, positive correlations were found between MHC I and age (r=0.93; P<0.05) and the weight of the animals (r=0.94; P<0.01). PFK (means of 175+/-179-374+/-181), CS (means of 100+/-23-126+/-38 MUmol/min/gdw) and MHC content indicated that energy provision in the impala is produced to a large extent via oxidative pathways and fibre types vary with animal characteristics. PMID- 22062820 TI - Variations in product-related parameters during the standardised manufacture of a semi-dry fermented sausage. AB - In the industry there is a tendency to shorten production processes of semi-dry fermented sausages (SFDS). Emerging problems then are generally related to product flavour and texture. Five batches of the same product were produced under pilot-plant conditions, following strictly standardised procedures. At pre determined time intervals in the early ripening stage weight loss, pH and a(w) values were recorded and Uniaxial compression tests were performed on cylindrical axial product samples. Uniaxial compression was introduced as a potential new methodology for determining the consistency of fermented sausages. The compression data were used to calculate stress and strain at fracture and Young's modulus. Despite careful standardisation of both the product formulation and the manufacturing process, the various parameters showed considerable variation. As anticipated, there was significant product weight loss, and decrease in pH and a(w) during the manufacturing process. Analyses of variance showed that neither stress, strain nor Young's modulus changed significantly over the period from 2-9 days. However, the averages of the Young's modulus tended to increase with time. These results suggest that the Young's modulus may become an important production parameter, in addition to the already applied product pH, a(w) and weight loss. PMID- 22062821 TI - Comparison of a natural rosemary extract and BHA/BHT for relative antioxidant effectiveness in pork sausage. AB - A commercial rosemary extract was evaluated for antioxidant effectiveness at concentrations of 1500 and 2500 ppm in frozen and precooked-frozen pork sausage, and from 500 to 3000 ppm in refrigerated, fresh pork sausage. Thiobarbituric acid reactive substances (TBARS), objective color values and sensory panel scores, were assessed. For refrigerated sausage, the rosemary extract at 2500 ppm was equally effective as butylated hydroxy anisole (BHA)/butylated hydroxy toluene (BHT). Similarly, the rosemary extract was equally effective as BHA/BHT in maintaining low TBARS values of precooked-frozen sausage. However, the rosemary extract was more effective than BHA/BHT for preventing increased TBARS values or loss of red color in raw frozen sausage. PMID- 22062822 TI - The eating quality of Canadian pork and its relationship with intramuscular fat. AB - This study was undertaken to assess the effect of various levels of intramuscular fat (IMF: <1%, 1.0-1.49%, 1.5-1.99%, 2.0-2.49% and 2.5-3.0%) produced from Canadian pigs on the eating attributes of pork loin. Sensory and instrumental eating attributes were determined on 85 pork loins (m. longissimus lumborum and thoracis). The following correlations were found between IMF and eating attributes: softness, -0.32 (P<0.01); initial tenderness, -0.31 (P<0.01); chewiness, -0.27 (P<0.01); rate of breakdown, -0.20 (P=0.07); juiciness, 0.17 (P>0.05); flavour intensity, 0.24 (P=0.02); off-flavour, 0.13 (P>0.05); mouth coating, 0.13 (P>0.05); amount of perceptible connective tissue, -0.02 (P>0.05), and instrumental tenderness (Warner-Bratzler shear force), -0.41 (P<0.001). As tenderness is considered the most important attribute that determines overall acceptance of pork, the threshold level of IMF for ensuring a positive eating experience was identified as a function of the attributes describing tenderness. Increasing the level of IMF past 1.5% did not change (P<0.05) the panelists scores for softness and initial tenderness. Average shear force, an instrumental measure of tenderness, was higher (P<0.05) at less than 1% IMF but did not change past 1.0% IMF (P>0.05). It is proposed that the threshold level of IMF that will ensure a pleasing eating experience is 1.5% IMF. PMID- 22062823 TI - Characterization of the microbial flora from a traditional Greek fermented sausage. AB - The microbial flora of naturally fermented sausages was studied. Lactic acid bacteria were the dominant species at the end of fermentation in all 3 batches (ca. 10(8) cfu g(-1)). Enterobacteria, Pseudomonas, yeasts and aerobic spore formers decreased during fermentation and the ripening process and were below the detection limit in the end product. Enterococci exceeded 10(4)-10(5) cfu g(-1) during fermentation and remained constant at this level during ripening. Gram positive, catalase-positive cocci exceeded 10(5) cfu g(-1), except for batch 1, during the first days of fermentation and then decreased until the end of ripening (10(2)-10(4) cfu g(-1)). No pathogenic staphylococci, sulfite reducing clostridia or Salmonella spp. were detected. Listeria spp. occurred in the first days of fermentation but were eliminated by the end of whole process in all batches. Identification showed that the majority of lactobacilli isolated from MRS agar strains were assigned to the species of Lactobacillus plantarum and Lb. plantarum/pentosus. All the isolated strains from the mannitol salt agar belonged to the genus of Staphylococcus. The predominant species were Staphylococcus saprophyticus, Staphylococcus xylosus and Staphylococcus simulans. The tests used to characterize the lactic acid bacteria and staphylococci as well as their distribution on the three batches were also discussed. PMID- 22062824 TI - PSE-like turkey breast enhancement through adjunct incorporation in a chunked and formed deli roll. AB - A randomized complete block design with five treatments (100% pale, soft, and exudative-like (PSE-like), 100% PSE-like+1.5% collagen, 100% PSE-like+0.30% kappa /iota-carrageenan, 100% PSE-like+1.5% soy protein concentrate, and 100% Normal) and six replications was utilized to test the effects of meat raw material, turkey collagen (TC), soy protein concentrate (SPC), and carrageenan (CG) on protein functionality in the formulation of chunked and formed turkey breast. Addition of 1.5% SPC and 1.5% TC both decreased (P<0.05) cooking loss and increased (P<0.005) the protein bind of treatments formulated with 100% PSE-like raw material. Purge loss decreased (P<0.05) in PSE-like raw material when 1.5% TC, 1.5% SPC, or 0.30% CG were utilized, and no differences (P>0.05) existed in consumer acceptability among treatments. This research demonstrates the potential to increase the water holding capacity and improve the texture of deli rolls from PSE-like raw material through the incorporation of collagen, soy protein, or carrageenan. PMID- 22062825 TI - Breed, slaughter weight and ageing time effects on physico-chemical characteristics of lamb meat. AB - The effects of breed, slaughter weight and ageing time on the meat quality of the three most important Spanish breeds were considered. Two hundred and twenty-five lambs of Rasa Aragonesa-local meat breed-, Churra-local dairy breed- and Spanish Merino were used. Animals (75 of each breed) were slaughtered at three different live weights (10-12, 20-22 or 30-32 kg), and the meat was aged for 1, 2, 4, 8 or 16 days. The meat pH, colour, amount of haem pigments, intramuscular fat, moisture, hydroxyproline content and sarcomere length were measured at 24 h post mortem. Meat texture was measured by compression after each ageing time. The pH of the samples ranged from 5.50 to 5.58. Meat colour varied with breed and slaughter weight (P?0.01), the M. longissimus thoracis was lighter in the youngest animals and in the Churra breed and redder in Merinos. Intramuscular fat increased and moisture decreased for heavier lambs. Differences in collagen were associated with breed (P?0.01); total and insoluble collagen contents were higher in the Churra breed. Sarcomere length was only slightly affected by slaughter weight. Meat from the Churra breed had the highest values at high levels of compression. Suckling lambs (10-12 kg) had greater myofibrillar toughness than heavier lambs and ageing strongly influenced myofibrillar tenderness. PMID- 22062826 TI - Performance and meat quality of organically versus conventionally fed and housed pigs from weaning till slaughtering. AB - The effects of organic nutrition on growth performance, meat and carcass traits in either a conventional or an organic housing unit from weaning till slaughtering were evaluated in terminal crossbreeds of a paternal line and a maternal 3-way crossbreed of Seghers hybrid. All pigs were reared in a conventional way from birth till weaning (4 weeks). One week after weaning they were moved to either a conventional or an organic barn. Eight pens of 4 pigs (2 barrows and 2 gilts) were held in both housing types. The study started when the pigs reached the age of 10 weeks. Half of the groups in each barn received a conventional diet, and the other half received an organic diet. Both feeds were isocaloric, neither of them contained antibiotic growth promoters. Three-phase feeding was applied. The organic housing led to a higher feed intake throughout the experiment (P<0.001), which resulted in a faster growth (P<0.001) but a lower meat percentage (P<0.05). Organic nutrition did not affect growth performance and carcass quality. Neither organic nutrition nor housing led to relevant differences in meat quality traits. PMID- 22062827 TI - Role of intrinsic search cues in the formation of consumer preferences and choice for pork chops. AB - This study investigates the role of drip, colour, marbling and fat cover as intrinsic search cues in the formation of pork chop preferences and individual determinants. Data are collected from a sample of 443 pork consumers in Belgium through using repeated selection of chops from randomised photobooks and questionnaires including socio-demographic, attitudinal and behavioural variables. Data analysis includes mixture regression analysis, bivariate descriptive statistics and the estimation of multivariate probit models. Consumers sampled in this study prefer pork chops without fat cover. Preference for fat cover is stronger among male, 35+ aged consumers with lower levels of awareness of the relation between food and health and who like pork for other reasons than taste and nutritional value (all p<0.05). Preference for colour is equally consistent within an individual, though fifty-fifty light-dark, with dark chops being more preferred by 35+ aged consumers (p<0.05). Preferences for marbling and drip are not consistent and not determined by joint socio demographic, attitudinal and behavioural factors. Preferences for cue levels are not correlated, except a weak relation between preference for dark chops without drip (r=0.116). Preferences are apparently formed by deductions with the use of single cues as key information, mainly based on fat cover or colour, and random choice on marbling and drip. PMID- 22062828 TI - Influence of minced pork and rind ratios on physico-chemical and sensory quality of Nham - a Thai fermented pork sausage. AB - The effects of incorporating varying levels of minced pork and rind on physico chemical and sensory quality of Nham were studied. An increase in cooked pork rind resulted in higher moisture, lipid, and initial pH values of Nham (P<0.05). However, no significant effects were observed on fermentation characteristics of Nham (P>0.05). At the end of fermentation, Nham with a higher meat component exhibited higher texture profile analysis force, hardness, and cohesiveness (P<0.05). The results suggested the importance of meat on the restructuring effect, which contributes to the texture formation of Nham. Incorporation of a higher amount of cooked pork rind improved water-binding properties, leading to decreased weight loss and released water. Based on the results of sensory evaluation, up to 43% pork rind can be used in the formulation with no adverse effect on texture and overall liking of Nham. However, the ratio of 5:5 was the most appropriate for minimising the cost of production. PMID- 22062829 TI - Effect of erythorbate, storage and high-oxygen packaging on premature browning in ground beef. AB - Premature browning (PMB) was investigated in ground beef patties with (0.04%, w/w) and without erythorbate. In Experiment 1, patties were stored at 4 degrees C for 48 h; at -18 degrees C for 21 days; or at -18 degrees C for 21 days, thawed at 4 degrees C for 24 h; and cooked. Bulk ground beef was stored at -18 degrees C for 24 days, thawed for 24 h at 4 degrees C, and patties prepared and cooked immediately. In Experiment 2, fresh patties were overwrapped with oxygen permeable film or packaged in 80% O(2)/20% N(2) (MAP), and stored for 48 h at 4 degrees C, or at -18 degrees C for 21 days, and cooked. Total reducing activity and color (L*, a* and b* values) were measured immediately prior to cooking. Patties were cooked to internal temperatures of 60, 66, 71 and 77 degrees C and internal cooked color was measured. Total reducing activity was higher for the erythorbate treatment than controls for all storage conditions (P<0.05). a* Values of cooked patties were higher for erythorbate than control treatments under all storage and packaging conditions at 60 and 66 degrees C (P<0.05). The presence of erythorbate in ground beef patties appeared to maintain red color at cooked internal temperatures of 60 and 66 degrees C. Frozen bulk storage appeared to increase the susceptibility of ground beef to PMB when compared to fresh and frozen patties. Patties cooked directly from frozen state appeared less susceptible to PMB than frozen-thawed and bulk storage. Ground beef appeared predisposed to PMB when stored in high-oxygen MAP at 4 degrees C for 48 h. PMID- 22062830 TI - Changes in colour characteristics and pigmentation of subcutaneous adipose tissue and M. longissimus dorsi of heifers fed grass, grass silage or concentrate-based diets. AB - The objective of this experiment was to determine the effect of dietary composition and duration of feeding on subcutaneous (s.c.) adipose tissue and M. longissimus dorsi (LD) colour and pigment concentrations of heifers. Fifteen heifers were permanently housed and fed a concentrate diet (PH-CON). Fifty-four heifers were grazed on pasture (PAS) for 90d, housed and offered concentrates (PAS-CON), 200g grass silage (GS)/kg dry matter (DM) (PAS-GS20), 500g GS/kgDM (PAS-GS50) or zero-grazed grass (PAS-GRA). To facilitate assessment of the temporal pattern of tissue colour, 3 heifers/treatment were slaughtered at housing (following 7d adjustment to diets) and 28, 56, 91 and 120 days thereafter. Yellowness ('b' value) of s.c. adipose tissue and lightness ('L' value) and redness ('a' value) of LD were recorded 48h post-mortem. beta-Carotene and lutein contents of s.c. adipose tissue and total LD haem pigments were determined. At housing, s.c. adipose tissue 'b' values of the PAS group (mean=13.47) were higher (P<0.01) than those of the PH-CON group (mean=10.35) but there was no difference in beta-carotene or lutein concentrations. The change in s.c. adipose tissue 'b' for each diet following housing was best described by the following equations: PH-CON: y=-0.087 (SE 0.0347) X+0.0005 (SE 0.00029) X(2)+10.06 (SE 0.600), MSE 1.94, R(2) 0.57, P<0.01. PAS-CON: y=-0.102 (SE 0.0286) X+0.0006 (SE 0.00024) X(2)+13.32 (SE 0.598), MSE 2.30, R(2) 0.62, P<0.001. PAS GS20: y=-0.106 (SE 0.0296) X+0.0008 (SE 0.00025) X(2)+13.10 (SE 0.618), MSE 2.46, R(2) 0.47, P<0.01. PAS-GS50: y=-0.077 (SE 0.0269) X+0.0006 (SE 0.00023) X(2)+13.29 (SE 0.552) MSE 1.95, R(2) 0.38, P<0.05. PAS-GRA: y=-0.018 (SE 0.0079) X+13.77 (SE 0.528), MSE 2.28, R(2) 0.24, P<0.05, where y='b' value, x=days post housing (d96-d216) and MSE=mean square error. Treatment had a significant effect on s.c. adipose tissue beta-carotene and lutein (both P<0.001) with PAS-GRA and PH-CON tending to have the highest and lowest concentrations, respectively. PH CON heifers tended (P=0.058) to have lower LD haem pigments and lighter LD than other heifers. It is concluded that, while concentrate feeding led to the greatest decrease in s.c. adipose tissue yellowness relative to PAS-GRA, choice of dietary ingredients and duration of feeding will depend on the stringency of the colour criteria in particular markets. PMID- 22062831 TI - Fatty acid profile, and chemical composition of Longissimus muscle of bovine steers and bulls finished in pasture system. AB - The objective of this work was to evaluate the conjugated linoleic acid content (CLA), the fatty acid profile, and the chemical composition of the Longissimus muscle (LM) of steers and bulls finished in pasture systems. Fourteen 1/2 Nelore*1/2 Aberdeen Angus cattle were studied. The animals were slaughtered at approximately 20 months of age, with an approximate final liveweight of 480kg. Moisture, ash, fat, crude protein, cholesterol, and fatty acid contents of Longissimus muscle were determined. Steer muscle had a higher lipid content (3.38%) than that of bulls (1.71%). Total n-3 fatty acids were higher in bulls. The amounts of CLA in steer and bull fat were similar, but the CLA content in steer muscle was higher (47.99mg100g(-1) in LM) than that in bull muscle (23.24mg100g(-1) in LM). PMID- 22062832 TI - Effect of vacuum-packaging storage on the quality level of ripened sausages. AB - To investigate the influence of vacuum-packaging on both the sensory properties and the degradation level of their lipid fraction, some ripened sausages (30 days) were further stored for 40 days under vacuum-packaging and compared to sausages kept unpackaged for the same period of time. The same kind of sausages was used in both the trials. As for the sensory properties, after storage the unpackaged sausages showed significantly higher mean scores of red intensity and global flavour than vacuum-packed ones (p<0.01 and p<0.05, respectively) indicating a brighter red colour of meat and a greater overall appreciation by the panelists. Regarding the degradation of the lipid fraction, significantly higher values (p<0.01) of the free fatty acids were detected in the vacuum-packed samples, indicating a greater hydrolytic degradation of their lipid fraction as compared to the sausages stored unpackaged. The oxidative degradation of the fatty fraction, measured by the combined use of conventional (determination of peroxide value and TBA test) and non-conventional techniques (HPSEC analysis of the polar compounds of the lipid fraction) showed significant increases during storage for both the storage conditions considered but no significant differences were found between packaged and unpackaged sausages. PMID- 22062833 TI - Comparative study of trace elements in certain fish, meat and meat products. AB - Selenium, copper, nickel, zinc, cadmium, manganese, iron, copper and lead contents of certain fish, meat and meat products consumed in Turkey were determined using inductively coupled plasma-optical emission spectrometry (ICP OES). The order of the elements in the meat, meat products and fish samples and their concentration ranges in MUg100g(-1) was Fe (57.7-156.4)>Zn (20-159)>Ni (8.2 24)>Pb (11.5-13.5)>Cr (8.44-9.51)>Cu (7.18-10.01)>Cd (0.77-1.04)>Mn (3.98-10)>Se (1.32-4.6). The elemental concentrations of fish studied seemed to be close to the international standards. The highest trace element concentrations were obtained from pastirma, meat and sausage while the lowest value was observed in Trachurus trachurus (saurel). Iron concentrations in all samples were higher than the recommended values. PMID- 22062834 TI - Microbiological quality of Australian sheep meat in 2004. AB - The third national baseline microbiological survey of Australian sheep carcases and frozen boneless sheep meat was conducted in 2004. Carcases (n=1117) sampled at 20 slaughter establishments were found to have a mean log total viable count (TVC, 25 degrees C) of 2.28 cfu/cm(2) and Escherichia coli was isolated from 43.0% carcases with a mean log 0.03cfu/cm(2) on positive samples. In samples from 10 boning (fabrication) plants (n=560) the mean log TVC for frozen boneless sheep meat was 1.85cfu/g and the mean log count for the 8.2% of samples with detectable E. coli was 1.39cfu/g. E. coli O157:H7 was isolated from 6/1117 carcases and from 1/560 boneless samples. Salmonella was isolated from 0/1117 carcases and from 3/560 samples of boneless product. Campylobacter sp. were isolated from 4/1117 carcases and from 1/560 boneless samples. Coagulase positive staphylococci were isolated from 23.4% to 32.7% of carcases and boneless sheep meat samples, respectively, with positive samples having a mean log count of 0.93cfu/cm(2) and 1.14cfu/g, respectively. The low level of bacteria described here is consistent with a very low risk to human health due to bacterial hazards in Australian sheep meat. PMID- 22062835 TI - Effects of ascorbic acid and OriganoxTM in different packaging systems to prevent pork lumbar vertebrae discoloration. AB - Darkening of bone marrow in packaged fresh pork is problematic and may be caused by pro-oxidative iron and (or) a pro-oxidative atmosphere. We evaluated the effects of ascorbic acid (AA) and OriganoxTM (OG) in different packaging systems to prevent pork lumbar vertebrae marrow discoloration. Concentrations of 1.25%, 1.875%, or 2.5% AA; 0.15% OG+0.30% AA; and 0.225% OG+0.45% AA were applied in 0.5 ml aliquots to 2.54-cm-thick pork lumbar vertebrae sections (n=288). Three packaging systems were used: high-oxygen (HiOx) modified atmosphere packaging (MAP), ultra-low-oxygen (ULOx) MAP, and polyvinyl chloride film (PVC). Vertebrae in HiOx MAP treated with 1.875% or 2.50% AA had superior (P<0.05) visual color to HiOx and PVC control by d 8. Antioxidant-treated vertebrae in HiOx had the highest (P<0.05) d 8 a(*) values. Vertebrae treated with 1.875% or 2.50% AA in ULOx MAP had the least (P<0.05) discoloration as assessed by a(*)/b(*) by d 8. Topical antioxidant application was very beneficial in preventing vertebrae discoloration in PVC and HiOx packaging systems. PMID- 22062836 TI - In-home consumer evaluations of individual muscles from beef rounds subjected to tenderization treatments. AB - In-home evaluations of the M. vastus lateralis, M. rectus femoris, M. semimembranosus, and M. adductor (n=266) muscles that were either blade tenderized, enhanced with a salt and phosphate solution, or served as a control (no tenderization or enhancement treatment) were conducted. Consumers (n=261) cooked these steaks and were asked to document cooking method and degree of doneness, and provide palatability ratings for each steak. Enhancing round muscles with a salt and phosphate solution improved most palatability traits compared to blade tenderized or control steaks. For M. semimembranosus and M. vastus lateralis, the enhanced steaks received higher (P<0.05) ratings for all palatability traits. Cooking method and degree of doneness had little influence on consumer palatability ratings, and where differences occurred, they were muscle specific. This may allow limited recommendations for the most appropriate cooking method and degree of doneness for specific beef round muscles. PMID- 22062837 TI - Molecular and technological characterization of Staphylococcus xylosus isolated from naturally fermented Italian sausages by RAPD, Rep-PCR and Sau-PCR analysis. AB - Coagulase-negative cocci (CNC) are important microorganisms in fermented sausages because they release lipases and proteases that are able to free short-chain fatty acids and peptides and aminoacids, respectively, that are responsible for the aroma of fermented sausage. The purpose of this study was to characterize Staphylococcus xylosus strains isolated from naturally fermented sausages, produced in three different processing plants in the Friuli Venezia Giulia region in the Northeast of Italy. Two hundred and forty-nine strains of S. xylosus were identified by species-specific PCR and subjected to molecular and technological characterization. RAPD-PCR with primer M13, Rep-PCR using primer (GTG)(5) and Sau PCR with primer SAG(1) were used for the molecular analysis, while the capability of the strains to grow at different temperatures and in the presence of NaCl and their lipolytic and proteolytic activity were tested in order to define the technological characteristics. The results obtained allowed us to differentiate strains coming from different plants, thereby admitting the presence of strains that are plant-specific. PMID- 22062838 TI - In vivo estimation of lamb carcass composition by real-time ultrasonography. AB - The objective of this study was to evaluate the accuracy of ultrasonography to measure fat thickness in live lambs and predict carcass composition to find a system that can assess carcass composition easily and accurately, without damage to the product and can improve carcass classification. Fat thickness (FTh) between the 12th and 13th ribs and between the 3rd and 4th lumbar vertebrae, was measured in vivo using real-time ultrasound, in 67 Churra Galega Bragancana males (mean weight 36.0kg, range 21.5-47.0kg), using an ALOKA SSD-500V equipped with two probes (5 and 7.5MHz) in order to predict carcass composition. The most satisfactory correlation between carcass and ultrasound measurements was between the 3rd and 4th lumbar vertebrae fat thickness (FTh). The first variable admitted in the models to predict carcass composition (live weight, LW) explained between 63% and 96% of the total variation of the weight of the components of the carcass. In fact, 96% of the variation in total amount of muscle was accounted for by live weight. The inclusion of the ultrasound measures with the 7.5MHz probe improved, in all prediction equations, the coefficient of determination (R(2)) with a substantial reduction in the residual standard deviation (RSD). In relation to the subcutaneous fat of the carcass, 85% of the variation was explained by live weight and the FTh 12-13 7.5 measurement. In the prediction model for total carcass fat weight, live weight and ultrasound fat thickness measurement explained 88% of the variation. The results indicate that in vivo ultrasound fat thickness measures in association with live weight can be used to predict carcass composition in Churra Galega Bragancana lambs. PMID- 22062839 TI - Classification of some heat-treated liver pastes according to container type, using heavy metals content and manufacturer's data, by principal components analysis and potential curves. AB - A total of 115 pork liver pastes were randomly collected in local markets from different brands, countries and containers. The concentrations of nine heavy metals (Cu, Ni, Cd, Fe, Mn, Pb, Cr, Co and Zn), determined by atomic absorption spectrometry, and some qualitative variables described on the labelling constituted the data set. Chemometrics analysis was performed combining principal components analysis (PCA), factor analysis (FA) and typical classification techniques, such as linear discriminant analysis (LDA) and potential curves (PoCu) to classify pork liver pastes. Origin of the sample, manufacturer and effect of manufacturing process were taken into account to verify traceability, which is an important issue in food safety policies. PMID- 22062840 TI - Effect of irradiation of frozen meat/fat trimmings on microbiological and physicochemical quality attributes of dry fermented sausages. AB - Changes in microbiological and physicochemical quality attributes resulting from the use of irradiation in the production of Greek dry fermented sausage were investigated as a function of fermentation/ripening time. Results showed that irradiating meat/fat trimmings at 2 or 4kGy prior to sausage production eliminated natural contamination with Listeria spp., and reduced pseudomonads, enterococci and pathogenic staphylococci, and enterobacteria, to less than 2 and 1logcfug(-1), respectively. Pseudomonads were very sensitive (>3.4 log reduction) to either radiation dose. Yeasts were the most resistant followed by inherent lactic acid bacteria; their reductions on the trimmings were radiation dose dependent. Residual effects of irradiation were noted against enterococci, but not against gram-negatives which died off fast during fermentation even in non irradiated samples. Growth of the starter bacteria, Lactobacillus pentosus and Staphylococcus carnosus, inoculated in the sausage batters post-irradiation was unaffected by the 2 or 4kGy pre-treatment of the trimmings. Irradiation had little or no effect at the end of ripening period (28 days) on pH, moisture content and color (parameters L(*), a(*), and b(*)). Changes in TBA values were small but statistically significant with irradiated samples having higher TBA values than control samples. PMID- 22062841 TI - Effects of potassium lactate, sodium chloride, sodium tripolyphosphate, and sodium acetate on colour, colour stability, and oxidative properties of injection enhanced beef rib steaks. AB - This study determined the effects of potassium lactate (KL), sodium chloride, sodium tripolyphosphate, and sodium acetate on colour, colour stability, and oxidative properties of injection-enhanced beef rib steaks. Enhancement solutions (8.5% pump) contained combinations of KL (0% or 1.5%), sodium chloride (0.3% or 0.6%), sodium tripolyphosphate (0% or 0.3%), and sodium acetate (0% or 0.1%). Steaks were packaged in a high-oxygen modified atmosphere (80% O(2)/20% CO(2)). Steaks with KL or KL and sodium acetate were darker but more colour stable (P<0.05) than control steaks. Steaks had less glossy surfaces when they contained acetate (P<0.05) and KL (P<0.11). Increasing sodium chloride content resulted in darker, less colour-stable steaks (P<0.05). Removing phosphate had little impact on colour (P>0.05). Both KL and sodium acetate improved visual appearance of injection-enhanced beef rib steaks, whereas the greater salt level were detrimental. PMID- 22062842 TI - Effects of potassium lactate, sodium chloride, and sodium acetate on surface shininess/gloss and sensory properties of injection-enhanced beef strip-loin steaks. AB - The objective was to determine the effects of potassium lactate (0% or 1.5%; KL), sodium chloride (0.3% or 0.6%), and sodium acetate (0% or 0.1%) on injection enhanced (8.5% pump), beef strip-loin steaks. All treatments contained 0.3% phosphate and 0.058% rosemary. Steaks were packaged in a high-oxygen modified atmosphere (80% O(2)/20% CO(2)) and were evaluated on d 2, 9, and 14 for surface shininess/gloss, shear force, and descriptive sensory attributes. As time in MAP progressed, oxidized, stale, and rancid flavours increased (P<0.05) and surface shininess/gloss decreased (P<0.05). Brown-roasted and beef flavours were most intense (P<0.05) on d 9. Using KL increased (P<0.05) brown-roasted and beef flavours and limited rancid flavour. Sodium acetate decreased (P<0.05) shear force. Adding more salt increased salty and rancid flavours (P<0.05). Sodium acetate and KL both improve sensory attributes of injection-enhanced beef. PMID- 22062843 TI - Bovine muscle 20S proteasome: I. Simple purification procedure and enzymatic characterization in relation with postmortem conditions. AB - Over the last decade, several sets of evidence support a possible contribution of the 20S proteasome to the meat tenderizing process. This assumption was emphasized by recent investigations demonstrating that the 20S proteasome was active in the absence of activators and exhibited endo- and exoproteolytic activities, a status often strongly debated before. In the present work, we developed a new rapid and simple purification procedure for muscle 20S proteasome and revisited the physicochemical properties of this complex in relation with the postmortem muscle environmental conditions, i.e. temperature, pH, osmolarity, etc. From a crude extract obtained from freshly excised muscle tissue, reasonable amounts of highly pure proteasome were prepared within a maximum of 4 days using only three chromatography steps. This purified proteasome was used to investigate the effect of pH, temperature, ionic strength and sodium dodecyl sulphate (SDS) on the major hydrolytic activities of this complex, i.e. trypsin-like (TL), chymotrypsin-like (CL) and peptidylglutamyl peptide hydrolase (PGPH) activities. Taken together, the data obtained suggest that the 20S proteasome constitutes a high hydrolytic potential in postmortem muscle conditions. To attest this finding, the 20S proteasome was further quantified by ELISA in at death and postmortem muscles including Longissimus, Rectus abdominis, Diaphragma pedialis and Tensor fascia latae bovine muscles. The primary conclusion was that time course changes in proteasome concentrations were not dependent on the kinetics of the pH fall. Secondly, the proteasome concentration in conditioned meat was in good agreement with previously reported proteolytic activity. Furthermore, the decrease in the muscle proteasome concentration can be considered as slow and this is particularly true in type 1 muscles for which the decrease in the amount of this complex did not exceed 7% during the first three days postmortem. This would suggest that the 20S proteasome was relatively stable during meat conditioning, a feature supporting a potential role in the meat tenderizing process. PMID- 22062844 TI - Bovine muscle 20S proteasome. II: Contribution of the 20S proteasome to meat tenderization as revealed by an ultrastructural approach. AB - The role of the 20S proteasome proteolytic effects was revisited using an ultrastructural approach with the aim to explain some particular structural changes identified in type I muscles and in high pH meat. In both types of meat, major changes observed after ageing are an increase in the thickness of the Z line followed by the appearance of an amorphous protein structure spreading out over the I-band. This was followed by a total degradation of this amorphous structure and of the Z-line. Partial transversal fragmentation of the myofibrils within the I-band can also be detected. The data reported clearly demonstrate that the 20S proteasome was able to mimic these sequential structural changes, a feature never obtained with either calpains or cathepsins. It is the first time that a direct implication of this complex in postmortem muscle is postulated. PMID- 22062845 TI - Bovine muscle 20S proteasome. III: Quantification in tissue crude extracts using ELISA and radial immunodiffusion techniques and practical applications. AB - The 20S proteasome is a large complex (700kDa) that exhibits endo- and exo peptidase activities with wide specificity. In postmortem muscles, several sets of evidence suggest a possible significant contribution of proteasome to meat tenderisation. Hence, an accurate and rapid quantification procedure is needed to attest that new function during the ageing of meat. In the present work, we developed an ELISA test enabling the quantification of nM concentrations of the 20S proteasome. We further tested the radial immunodiffusion (RID) technique described as a more simple method that can quantitatively determine the concentration of an antigen in a complex mixture. The ELISA test allowed us to quantify the 20S protesome in tissue homogenates and fluids with a recovery of 100%, a coefficient of variation lower than 5% and a detection limit of 9ng/ml. Quantification of the 20S proteasome in various bovine tissue by ELISA showed the highest concentration in liver followed by spleen and kidney, with muscles exhibiting the lowest concentrations. In addition, measurement of the proteasome concentration in eight different bovine muscles with various metabolic profiles led to the conclusion that the relationship between muscle metabolic properties and proteasome concentration is rather complex. Nevertheless, heart muscle exhibited the highest proteasome content (331MUg/g wet tissue) whereas the lowest values were found for M. Tensor Fascia Latae (213MUg/g wet tissue), a fast twitch white muscle, M. Supraspinatus (209MUg/g wet tissue), a slow twitch red muscle and M. Pectoralis profondus (203MUg/g wet tissue), an intermediate muscle. As compared to other endogenous peptidases, muscle tissue contains relatively high amounts of proteasome. Hence this complex can be quantified using the RID, which allows quantification of protein in the MUg range. Plotting the concentration values determined with both methods for all bovine tissues tested gave a straight line with a correlation coefficient of 0.99. PMID- 22062846 TI - Sensitivity of three pathogenic bacteria to Turkish cemen paste and its ingredients. AB - Pastirma is a dry cured meat product which is pasted with cemen. This paste is prepared from ground fenugreek, garlic and red hot pepper (RHPP). In this study, the cemen mix/paste and all its ingredients were tested for their inhibitory effects on Escherichia coli, Staphylococcus aureus and Yersinia enterocolitica. All samples had a varying inhibitory effect against all the bacteria tested during 4 days of storage. Complete cemen paste showed the strongest inhibitory effect on the three pathogens compared to ingredients alone. Fenugreek and RHPP had a bacteriostatic effect while the cemen paste and garlic had a bactericidal effect. S. aureus was the most sensitive bacterium while Y. enterocolitica was the most resistant. The results of this study confirmed the protective effect of cemen paste and garlic in food preservation especially against E. coli, S. aureus and Y. enterocolitica proving safety for public health. Hence it might be concluded that cemen paste is the first hurdle to prevent bacterial contamination, and a low pH (~4.83) value would also add an additional barrier to secure safety of the product. Finally, it can be suggested that similar studies should be conducted on actual meat systems to confirm these findings. PMID- 22062847 TI - Myosin heavy chain fibre types and fibre sizes in nuliparous and primiparous ovariectomized Iberian sows: Interaction with two alternative rearing systems during the fattening period. AB - To investigate the effects of the reproductive background (nuliparous/primiparous) on skeletal muscle phenotype and their interaction with two alternative finishing systems (indoors/outdoors) in Iberian sows, 32 contemporary piglets were assigned to four different groups: indoors-nuliparous, indoors-primiparous, outdoors-nuliparous and outdoors-primiparous. Nuliparous sows were ovariectomized at 4 months of age, whereas primiparous were castrated at 14 months of age, after their first lactation. Indoors sows were fattened (2 months prior to slaughter) intensively, whereas outdoors sows were finished in an extensive land with natural resources. Muscle samples (semimembranosus, gluteobiceps) were analyzed for myosin fibre types and fibre sizes. Sows finished out-of-doors had more type I and IIA fibres and smaller fibres than indoor fattened pigs. Primiparous reared indoors had a significantly lower IIX:IIB fibre ratio and showed a clear tendency for having larger fibres than nuliparous reared indoors. Reproductive background effect interacted with rearing condition effect inducing relevant muscular adaptations. Thus, the influence of reproductive background on muscle characteristics was not significant in sows reared out-of doors but highly significant in sows finished intensively. This interaction resulted in muscular traits less favourable for meat quality in primiparous vs. nuliparous reared indoors. PMID- 22062848 TI - Changes in Zn-porphyrin and proteinous pigments in italian dry-cured ham during processing and maturation. AB - Substitution of iron with zinc in myoglobin during maturation of Parma ham to yield zinc porphyrin extractable by 75% vol/vol acetone/water solution and detectable by fluorescence spectroscopy, was found to occur concomitant with protein modification in myoglobin. The content of zinc porphyrin increases throughout the whole processing and maturation of Parma ham, from I(fl) 0.1+/ 0.06 for green ham to I(fl) 84.4+/-48.8 for fully matured Parma ham. In an aqueous extract of Parma ham with pH 6.0 protein alteration in myoglobin, as detected by size-exclusion chromatography, is initiated during the resting period following salting and seems to precede formation of zinc porphyrin. During maturation the results indicate that the modified myoglobin could undergo polymerization, and it is suggested that initial protein denaturation or degradation facilitates substitution of iron with zinc. The pigment polymerization may be a result of non-covalent protein association to zinc porphyrin in denatured or partly degraded myoglobin. PMID- 22062849 TI - Influence of rosemary-tocopherol/packaging combination on meat quality and the survival of pathogens in restructured irradiated pork loins. AB - Irradiated restructured pork loins treated with rosemary-tocopherol/double packaging had lower TBARS values than vacuum-packaged control after 10 days of refrigerated storage. The rosemary-tocopherol combination, however, had no effect on the production of sulfur volatiles responsible for the irradiation off-odor, and color changes in irradiated pork. V7/A3 double-packaging was effective in reducing the sulfur volatiles significantly. Rosemary-tocopherol combination was highly effective in reducing the volatile hexanal in irradiated restructure pork. Irradiation was effective in reducing Listeria monocytogenes and Salmonella typhimurium inoculated on the surface of restructured pork loin in dose-dependent manner. The irradiation D(10) values for L. monocytogenes and S. typhimurium were 0.58 and 0.55kGy, respectively. During the 20 days of refrigerated storage, L. monocytogenes in both nonirradiated and irradiated samples grew gradually, but the number of S. typhimurium decreased. The added rosemary-tocopherol, however, showed little bacteriocidal effects to L. monocytogenes and S. typhimurium. PMID- 22062850 TI - Pre-slaughter transport, AMP-activated protein kinase, glycolysis, and quality of pork loin. AB - Numerous studies have revealed that pre-slaughter stress, like transport, increases the occurrence of pale, soft, and exudative (PSE) pork meat. The molecular mechanism underlying this phenomenon, however, is poorly defined. In this study, we investigated the effects of pre-slaughter transport and subsequent rest on energy metabolism, AMP-activated protein kinase (AMPK) activation, and glycolysis in postmortem pork loin. Results indicated that pre-slaughter transport accelerated ATP depletion, which led to lower energy status in postmortem muscle immediately post-exsanguination when compared with control. The lower energy status led to AMPK activation within 1h postmortem, subsequently increasing glycolysis, leading to rapid glycolysis and high incidence of PSE meat. Allowing pigs to rest after transport restored energy status in muscle ante mortem. Higher energy status then prevented premature and rapid AMPK activation in postmortem muscle and lessened the negative effects of pre-slaughter transport on meat quality. AMPK regulated glycolysis in postmortem muscle, at least partially, through phosphorylation and activation of phosphofructose kinase-2, since fructose-2,6-diphosphate content, an allosteric activator of phosphofructose kinase-1, was well correlated with AMPK activation and glycolytic rate. This suggests that AMPK is a potential molecular target for the control of PSE incidence in pork. PMID- 22062851 TI - Effect of natural and synthetic antioxidants on protein oxidation and colour and texture changes in refrigerated stored porcine liver pate. AB - The antioxidant effect of two plant essential oils (sage and rosemary) and one synthetic antioxidant (BHT) on refrigerated stored porcine liver pate (4 degrees C/90 days) was evaluated. Pates with no added antioxidants were used as controls. Liver pates were analysed for protein oxidation, modification of heme (HI) and non-heme iron (NHI) concentrations, and colour and texture characteristics at days 0, 30, 60 and 90 of refrigerated storage. The amount of carbonyls from protein oxidation significantly (p<0.05) increased during refrigerated storage, and this increase was significantly higher in the control pates than in their treated counterparts. Antioxidants successfully protected heme molecules from degradation and significantly inhibited the increase of NHI in refrigerated stored liver pates. Colour changes seemed not to be directly related to oxidative processes since pates with added antioxidants suffered greater colour modifications than the controls. The addition of rosemary essential oil significantly reduced hardness of liver pates. Sage and rosemary essential oils exhibited similar antioxidant properties to BHT denoting their suitability as alternatives to synthetic antioxidants. PMID- 22062852 TI - Effect of starch type and its modifications on physicochemical properties of bologna-type sausage produced with sheep tail fat. AB - Gelatinized, solubilized/dispersed and retrograded starches were produced from normal (unmodified) corn and potato starches, and were used with sheep tail fat for sausage batters. Emulsion stability, jelly and fat separation, water holding capacity (WHC), emulsion viscosity and batter pH were determined. Penetrometer reading after cooking of the batters, and tenderness of the end-product were determined. Modified starches statistically (p<0.01) affected emulsion stability and emulsion viscosity. The modification process was not significant for pH, WHC, jelly and fat separation and penetrometer values (p>0.05). While type of used starch had a significant effect on jelly and fat separation (p<0.05), for the other measurements it was not significant (p>0.05). PMID- 22062853 TI - Improvement of shelf-life of buffalo meat using lactic acid, clove oil and vitamin C during retail display. AB - Buffalo meat steaks dipped in either (1) distilled water (control), (2) lactic acid (LA), (3) LA+clove oil (clove), or (4) LA+clove+vitamin C (Vit C) were displayed at 4+/-1 degrees C, illuminated by a standard fluorescent lamp. The pH, 2-thiobarbituric acid reactive substances (TBARS), instrumental colour (CIE L(*), a(*), b(*)), aerobic plate counts (APC), psychrotrophic counts (PPC), coliform counts and sensory colour and odour were determined up to 12th day of display at 3 days interval. Results showed that, all the treatments have significantly (P<0.05) reduced the TBARS values compared to control. Among treatments, use of LA+clove has exhibited significantly (P<0.05) lowest TBARS values throughout display period than others. Buffalo meat steaks treated with either LA+clove or LA+clove+Vit C had significantly (P<0.05) lower APC, PPC and coliform counts than control or LA treated samples. LA+clove+Vit C treated samples maintained significantly (P<0.05) higher a(*) and b(*) values during display as well as improvement in sensory colour and odour than others. Treatment with either LA+clove or LA+clove+Vit C extended the display life of buffalo meat steaks at 4+/-1 degrees C. There appears to be a significant advantage to using LA+clove or LA+clove+Vit C over LA alone. PMID- 22062854 TI - In vivo prediction of carcass composition and muscularity in purebred Texel lambs. AB - A subjective assessment of the shape of the hind limb of purebred Texel lambs was evaluated as an in vivo predictor of carcass composition and muscularity. Lambs were taken from two flocks that were managed in a common environment, but which had either been selected for lean tissue growth rate or for improved conformation. Lambs were slaughtered at a mean age of 139 days at the end of an 11 week performance test in which they were reared indoors on a concentrate diet. Pre-slaughter measurements of live weight and ultrasonic muscle (UMD) and fat (UFD) depths at the position of the third lumbar vertebra, body length (L) and a subjective leg shape score were recorded. After slaughter, measurements were recorded for carcass side length (SL), leg length (T) and the maximum width (A) and depth (B) of the longissimus thoracis and lumborum (LTL) muscle. The side was fully dissected and various muscle weights and skeletal dimensions were used to calculate indices of muscularity as ?(muscle weight/length) per unit length or as UMD/L, A/SL or B/SL. The leg shape score was positively correlated with lean weight (0.23) and proportion (0.24), lean:bone ratio (0.25), measures of LTL dimensions (0.27-0.38) and muscularity traits (0.27-0.57) but was not significantly (P>0.05) correlated with fat weights or proportions in the carcass. Live weight was the best single predictor of lean weight (RSD=0.403) and the addition of leg shape score (RSD=0.381) to prediction equations was less effective than the inclusion of UMD and UFD in combination (RSD=0.357). The addition of leg shape score to equations that included ultrasonic traits gave a significant (P<0.05) but marginal improvement in prediction (RSD=0.347). The leg shape score was the most useful in vivo predictor of carcass muscularity traits and, with R(2) in the range 0.30-0.50, had comparable predictive power to a leg muscularity score derived from muscle weight and femur length. It is concluded that the leg shape score showed potential as a predictor of carcass muscularity that was largely independent of live weight and fatness at a fixed age and was marginally associated with superior lean yield and lean:bone ratio. PMID- 22062855 TI - Influence of the time of year on the incidence of PSE and DFD in Irish pigmeat. AB - The conditions of PSE (pale, soft, exudative) and DFD (dark, firm, and dry) are significant causes for downgrading of pigmeat resulting in financial loss to the slaughter plant. The objective of this study was to document the variation in quality of pigmeat from one slaughter plant over a 15-month period, based on colour, appearance and pH. During 4 days of most weeks, 30 pigs were randomly selected from the slaughter line, resulting in a total number of 4560 pigs. Muscle pH between the third and fourth rib was measured 45 min, 90 min and 24 h after slaughter. Using a Minolta colorimeter (Hunter L, a, b scale), colour of the longissimus dorsi muscle was measured 24 h after slaughter. Muscle colour was also visually scored on a scale of 1-6. Carcass pH at 24 h post-mortem varied significantly with month of slaughter (P<0.04) as did colour (Hunter L, P<0.001; Hunter a, P<0.001; Hunter b, P<0.001). It was concluded that meat quality as measured by 24 h pH and colour was poorest during the months of November and December. While this may be at least partly related to weather, it is probable that the increased slaughtering rates at this time and variable resting period before slaughter had the biggest impact. PMID- 22062856 TI - Effects of PSE on the quality of cooked hams. AB - Meat quality comparisons were carried out on hams produced from pork legs showing evidence of PSE and normal pork legs. Quality measurements included drip loss, sliceability, cooking loss, TBARS analysis and colour evaluation (Hunter L, a, b). A total of 40 pork legs were selected from a commercial slaughtering plant, 20 from carcasses showing PSE and 20 from normal carcasses based on L, a, b, and pH values. Carcass pH taken between the third/fourth rib was measured 45 min, 90 min, and 24 h after slaughter. Using a Minolta colorimeter (Hunter L, a, b,), colour of the Longissimus dorsi muscle was measured 24 h after slaughter. PSE had an adverse effect on cooked hams in comparison to normal cooked hams with respect to driploss (P<0.01), cooking loss (P<0.01), sliceability (P<0.01), colour (P<0.05) and lipid oxidation (P<0.05). Cooked hams manufactured from severe PSE pork in this study had an estimated financial loss of 50% (IRLL4.90) in comparison to those manufactured from normal pork (IRLL9.80). PMID- 22062857 TI - Development and evaluation of a cabrito smoked sausage product. AB - In order for the meat goat producer to survive, new avenues for marketing goats must be created. Currently, the live animal is sold directly to consumers, or to brokers who in turn sell the animal directly to consumers or retail stores that cater to various ethnic groups. The production of value-added products with appeal to North American consumers, as well as current ethnic consumers, should result in increased profitability of the meat goat. The objectives of this study were to develop a value added product, cabrito smoked sausage, using goat meat as the sole meat ingredient; evaluate soy protein concentrate (SPC) at various levels in an effort to reduce product cost; determine consumer acceptability; and conduct a cost analysis to determine the approximate market price for the product. Three fermented cabrito smoked sausage products were manufactured containing 0, 1.75 or 3.50% SPC and stored at 2+/-1 degrees C until evaluated. The sausages were evaluated for sensory characteristics, proximate analysis, pH, water activity and smokehouse yields. Trained panelists detected no significant flavor differences (P > 0.05) between the products. As a result of these findings, sausages formulated with 0 and 3.50% SPC were compared in a consumer sensory evaluation. Consumer panelists detected no significant differences (P > 0.05) in flavor, texture and overall acceptance between the snack sticks. Approximately 65% of the panelists commented that they would purchase the value added products. Proximates, pH, water activity and smokehouse yields were similar (P > 0.05) for the sausages formulated with 0 and 3.50% SPC. The addition of SPC resulted in an 8.79% reduction in the price of the 3.50% SPC formulation when compared to the sausage formulated with no SPC. PMID- 22062858 TI - Effect of processing plant on pork quality. AB - The impact of processing plant on pork quality was studied by assessing pork quality in three commercial plants (A, B, C). Plants differed in the layout of the races, stunning systems (A and B: electrical, C: CO(2) stunning) and chilling systems (A: rapid chilling, B and C: conventional). Factors not related to the processing plants (e.g. genetic background of animals, transport, lairage) were standardized. In total, nine batches of about 150 pigs each were processed. Each batch was purchased at a commercial farm and randomly divided into three groups for delivery to the three processing plants. Meat quality was evaluated by measuring early post-mortem muscle pH and temperature as well as ultimate pH, meat colour (Minolta Chroma Meter and Japanese colour scale), filter paper score (FPS), electrical conductivity (EC) and drip loss. Plant C produced an inferior quality compared to plants A and B: meat was paler (C: 2.8 vs. A: 2.9 and B: 3.0 on the Japanese colour scale) and had higher drip losses (C: 5.2 vs. A: 4.8 and B: 4.9%). Meat colour hardly differed between plants A and B but waterholding properties were best at plant A as indicated by FPS (A: 2.4 vs. B: 2.8 vs. C: 3.3) and EC (A: 5.4 vs. B: 6.4 vs. C: 7.4 mS). It is concluded that processing plant may influence meat quality. Correlations between early post-mortem measurements and meat quality traits were low. Nevertheless, high carcass temperatures and low pH values early post-mortem were shown to lead to inferior meat quality. PMID- 22062859 TI - Relationships between dietary fatty acid composition and either melting point or fatty acid profile of adipose tissue in broilers. AB - Data on the fatty acid composition of the diet and that of the adipose tissue in broilers were collected from the literature. The linear regression between the dietary and the adipose tissue unsaturated to saturated fatty acids ratio (U/S ratio) was calculated because the U/S ratio of adipose tissue fat determines its melting point, which is an indicator of the consistency of poultry fat. For 54 data points from three different experiments, the linear correlation coefficient of the relationship between dietary and adipose tissue U/S ratio was 0.77. The regression equation for linoleic acid in adipose tissue as a function of dietary linoleic acid was calculated. The linoleic acid content of adipose tissue was expressed as weight percentage of total fatty acids. Intake was expressed as either weight percentage of total fatty acids or as energy percentage of total dietary metabolizable energy. The linear correlation coefficients were 0.68 and 0.78 as based on 116 or 91 data points from 15 or 12 different experiments. Significant correlations were also found for alpha-linolenic acid. The linoleic acid content of adipose tissue was found to be correlated (r=0.87) for 25 data points with that in consumable broiler meat, which may affect serum cholesterol concentrations in humans. With the help of the regression formulas presented it may be possible to formulate broiler diets in relation to consumer health and product quality. PMID- 22062860 TI - Batch accuracy of on-line fat determination. AB - A new method for determination of the fat content of large meat batches without sampling is presented. It is based on dual-energy X-ray (DXR) scanning of meat trimmings prior to mixing, in order to determine the exact fat content of the resulting meat batch. Twenty-seven samples of three types of pork trimmings with a fat content ranging from 24 to 63% were collected and combined into batch sizes of 27-241 kg. At small batch sizes (27 kg) the nature of the measurement error is mainly random, resulting in a prediction error (root mean square error of prediction) of 0.57% against the reference method. At a batch size of 241 kg the error was reduced to 0.34%. The DXR method determines the fat content of all meat in a batch without any sampling required, thus reducing the sampling error to a minimum. This is essential, as the results show that the sampling error is large: when 27-kg samples were homogenized and measured by the reference method, the standard deviation of high-fat samples was 4.7%. PMID- 22062861 TI - Degradation of gamma- and alpha-tocopherol and formation of 5-nitro-gamma tocopherol induced by peroxynitrite in liposomes and skeletal muscle. AB - Peroxynitrite, formed from the reaction between nitric oxide and superoxide, can participate in free radical-mediated reactions with cellular components in muscle to (1) initiate lipid oxidation via the production of lipid hydroperoxides, and (2) produce novel nitrated products. 5-Nitro-gamma-tocopherol (NGT) is formed by the electrophilic substitution reaction between peroxynitrite and gamma tocopherol. The objective of this research was to examine the utility of NGT as a lipid-phase, peroxynitrite-specific biomarker in muscle foods. NGT was detected when exogenous peroxynitrite was added to liposomes containing gamma-tocopherol and homogenates from chicken dark and turkey light muscle with added gamma tocopherol. Detectable levels of NGT were not observed in either minced turkey light muscle stored at -20 degrees C or chicken dark muscle stored at 4 degrees C. These results suggest that NGT is not a suitable biomarker to confirm the presence of endogenously produced peroxynitrite in muscle foods. PMID- 22062862 TI - Reflectance at 610 nanometers estimates oxymyoglobin content on the surface of ground beef. AB - This research evaluated the utility of direct (K/S 610/K/S 525) and indirect (100%-% deoxymyoglobin+% metmyoglobin) methods for estimation of oxymyoglobin (OMb) on the surface of ground beef. Direct estimation was highly correlated to visual color scores (r=-0.93), indirect determination of OMb (r=0.98), and % metmyoglobin (r=-0.98). Since indirect OMb was based partially on % deoxymyoglobin, which was poorly correlated to visual color scores, the accuracy of the subtraction method may be limited. Both direct and indirect methods produced similar variability when estimating OMb. All calculations for pigment forms produced outliers, which were adjusted to 0 and 100% to more precisely represent surface pigment concentrations. This work suggests that the K/S 610/K/S 525 method is accurate and repeatable and can be used to quantify surface OMb concentration and discoloration of ground beef. PMID- 22062863 TI - Purification and characterization of a novel glutamyl aminopeptidase from chicken meat. AB - A novel glutamyl aminopeptidase (aminopeptidase A, EC 3.4.11.7) was purified from chicken meat by ammonium sulfate fractionation, ethanol fractionation, heat treatment, and successive column chromatographies of DEAE-Sepharose CL-6B and Sephadex G-200. The purified enzyme migrated as a single band on SDS-PAGE. The molecular weight of this enzyme was found to be 55,000 and 550,000 by SDS-PAGE and Sephadex G-200 column chromatographies, respectively. This enzyme hydrolyzed Glu- and Asp-, but not Leu-, Arg-, and Ala-2-naphthylamide (-2NA) at all. The optimum pH and temperature for hydrolysis of Glu-2NA was 7.5. and 70 degrees C, respectively. Reducing agents such as cysteine and dithiothreitol inhibited the activity of this enzyme at concentrations of 1 mM. However, the activation by Ca(2+) and the inhibition by amastatin were not observed. PMID- 22062864 TI - Growth parameters and meat quality of finishing hogs supplemented with creatine monohydrate and a high glycemic carbohydrate for the last 30 days of production. AB - The objective of this study was to evaluate the growth and meat quality of hogs supplemented with creatine monohydrate (CMH) and (or) a simple carbohydrate (dextrose) for the last 30 days of production. Crossbred market barrows (n=32; 75 kg) were blocked by weight and randomly allotted to one of eight pens with four animals per pen. Dietary treatments were a control (normal corn and soybean meal diet), CMH (control diet supplemented with 0.55% CMH), DEXT (control diet supplemented with 2.1% dextrose), and COMBO (control diet supplemented with CMH and DEXT). Average daily gain on test, fat depth, hot carcass weight, and LMA (postmortem dot grid measurement) were not affected by dietary treatment. However, a nonsignificant trend (P=0.07) was observed for 10th rib loin muscle area (LMA) gain on test as determined by real-time ultrasound comparisons over the course of the 30 days feeding duration (COMBO=4.24 cm(2) increase vs. control=1.0 cm(2) increase). No significant differences in pork quality were noted across treatment groups. PMID- 22062865 TI - Sensory and chemical assessment of pork supplemented with iron and vitamin E. AB - Pork muscle samples (M. longissimus dorsi and M. psoas major) were obtained from pigs given one of four dietary treatments, (1) control diet, (2) supplemental iron (7g iron (II) sulphate/kg feed), (3) supplemental vitamin E (200 mg dl-alpha tocopheryl acetate/kg of feed) and (4) supplemental vitamin E+supplemental iron. Vitamin C was supplemented to all dietary treatments to facilitate iron uptake. Vitamin E and iron tissue levels were determined for each treatment. Warmed-over flavour (WOF) was evaluated by a trained sensory panel (n=8) for the four treatments which were cooked and refrigerated at 4 degrees C for up to 5 days. Thawing loss, driploss and thiobarbituric acid reactive substances (TBARS) were also determined. Vitamin E muscle tissue levels were greatest in the Iron/vitamin E-treated group followed by the vitamin E group, control and iron treated groups, respectively for M. longissimus dorsi. Whereas, for M. psoas major vitamin E tissue levels were in order of magnitude, vitamin E>iron/vitamin E>iron>control group. Iron tissue levels were in the order vitamin E>iron/vitamin E>control>iron for M. longissimus dorsi and iron>vitamin E>control>iron/vitamin E for M. psoas major. Thus, vitamin E and vitamin C promoted non-supplemental iron absorption in the vitamin E-treated group for M. longissimus dorsi and to a lesser extent for M. psoas major. M. psoas major was more susceptible to warmed-over flavour development than M. longissimus dorsi for all treatments as determined by sensory profiling, due to higher tissue iron levels. From sensory profiling, WOF development in M. longissimus dorsi and M. psoas major was highest in the iron supplemented groups followed by the control and vitamin E-supplemented groups. PMID- 22062866 TI - The influence of post-mortem ageing and roasting on the microstructure, texture and collagen solubility of bovine semitendinosus muscle. AB - Bovine semitendinosus (ST) muscles aged for 5 and 12 days at 4 degrees C were roasted at 170 degrees C to internal temperatures of 50, 60, 70, 80 and 90 degrees C. Microstructural changes in meat were evaluated using a scanning electron microscope (SEM). Texture profile analysis (TPA) and measurements of the shear force values of samples were conducted using a texture analyser. The cooking losses and quantity of total and soluble collagen were also estimated. The structure of intramuscular connective tissue and myofibrillar structure of meat after 5 days of ageing was very regular. In 12-day-aged samples fibrous and myofibrillar structures were less distinct, damages of endomysium tubes appeared and fibres of perimysium were swelled. Ageing of ST muscle for 12 days caused a two-fold increase in the quantity of soluble collagen and a two-fold decrease in the value of TPA parameters-hardness and chewiness, as compared to 5-day-aged samples. The decrease in fibre diameter and sarcomere length during roasting started at 60 degrees C in 5-day-aged meat and at 50 degrees C in 12-day-aged samples. The shear force values measured after roasting were lower for 12-day aged meat than for 5-day-aged samples. The quantity of soluble collagen in roasted meat increased at an internal temperature of 80 degrees C. At a higher temperature of meat this variable depended on the degree of meat ageing. The cooking losses during roasting of meat were about 3% lower for 12-day-aged than for 5-day-aged samples. In the examined range of internal temperature of meat the cooking losses and the sarcomere length were negatively correlated. PMID- 22062867 TI - The effects of carrageenan and pectin on some quality characteristics of low-fat beef frankfurters. AB - Effects of carrageenan (0.3, 0.5, or 0.7%) and carrageenan (0.3, 0.5, or 0.7%) with a pectin gel (20%) on some quality characteristics of low-fat beef frankfurters were evaluated in comparison to a high-fat control (HFC) and a low fat control (LFC). While low-fat frankfurters had <3.0% fat, 73-76% moisture, 13 14% protein, HFC had 17% fat, 59% moisture, and 14% protein. A reduction of 50 59% in cholesterol was determined in low fat beef frankfurters as compared to HFC (P<0.05). Better process yield and emulsion stability, and less purge were observed with increasing carrageenan concentration. Treatment groups showed higher water holding capacity (WHC) than LFC, and lower WHC than HFC (P<0.05). With increasing carrageenan concentration, WHC increased and penetrometer value decreased in low-fat frankfurters. PMID- 22062868 TI - Storage stability of low-fat beef frankfurters formulated with carrageenan or carrageenan with pectin. AB - Storage stability of low-fat frankfurters (<3.0 fat content) formulated with carrageenan (0.3, 0.5, and 0.7%) or carrageenan with a pectin gel (PG) (20%) was examined during 49-day refrigerated storage. Low fat frankfurters had higher bacterial growth than high-fat control (HFC) over the refrigerated storage due to higher water activity resulting from extra water addition. While there was no change in the pH of low-fat frankfurters initially due to carrageenan or PG incorporation, the most noticeable pH decline was observed in PG-added frankfurters followed by only carrageenan added ones over the storage period. HFC had the highest (P<0.05) TBA value and the lowest redness index (a(*)/b(*)) all the time as compared with carrageenan or carrageenan and PG added low-fat frankfurters. Low-fat frankfurters formulated with either carrageenan or carrageenan with PG had acceptable sensory scores. PMID- 22062869 TI - Effect of castration on meat quality in Piemontese cattle. AB - The effect of early (5 month) or late castration (13 month) on meat quality of hypertrophied Piemontese cattle was investigated. Twenty four animals, equally divided into three groups (early castrated, EC; late castrated, LC; intact males, IM) were reared under the same experimental conditions and slaughtered at the same age. Twenty four hours after slaughter the pH was measured on the longissimus thoracis of the right side. After 11 days of ageing the following analyses were performed on the longissimus thoracis et lumborum: water, protein and ether extract contents, hydroxyproline content and collagen solubility, colour (L, a(L), b(L), hue and chroma), drip and cooking losses, Warner-Bratzler shear values and sensory analysis (appearance of the raw meat and eating qualities of the cooked meat). Compared with intact males, the castrates had lower water and hydroxyproline contents and higher contents of protein and ether extract. No significant differences were observed between early and late castration, except for cooking losses. PMID- 22062871 TI - Comparison of Infant Car Seat grip orientations and lift strategies. AB - The rear-facing Infant Car Seat (ICS) is designed to meet federal requirements for transporting children less than 1 year old. Typical use includes transfer in and out of a vehicle, which is shown to be a difficult lift. Despite the frequency of this lift, manufacturers provide little guidance for users. Review of relevant literature suggested an ICS featuring an angled handle, promoting a neutral wrist posture, would increase grip stability and decrease lifting effort. Popular press suggested a foot-in-car stance for the ICS lift would do the same. An experiment was conducted in which wrist deviations from neutral posture were recorded along with lifting muscle activation levels (multiple flexor muscles and biceps brachii) and overall perceived exertion for straight versus a new bent handle design and conventional stance versus foot-in-car. Foot position was examined to test the recommendations in the popular press. Surprisingly, wrist deviation was not significantly affected by the new bent handle design (due to compensatory behavior with the straight handle) but was related to foot placement (p=0.04). Results revealed the bent handle to significantly reduce flexor activation compared with the straight handle (p=0.0003); however, the level of biceps activation increased. Biceps activation also significantly increased for foot-in-car stance (p=0.035) but not flexor activation. In general, the bent handle enabled the user to lift the ICS with a steadier grip and less effort. PMID- 22062872 TI - Relationship of prepulse inhibition to temperament and character in healthy Japanese subjects. AB - Prepulse inhibition (PPI) of acoustic startle reflex (ASR) and personality, such as temperament and character, are considered candidate endophenotypes of schizophrenia. Gene polymorphism studies have provided evidence that both PPI and self-transcendence (ST) are polygenetic traits that involve several neurotransmitters, including the serotonin and dopamine signaling pathways. However, the relationship between PPI and temperament/character has not been properly addressed to date. Here, we investigated the link between PPI and temperament/character in 169 healthy Japanese subjects. A human startle response monitoring system was used to deliver acoustic startle stimuli and to record and score the electromyographic activity of the orbicularis oculi muscle. PPI was evaluated at signal-to-noise ratios (SnRs: intensity difference between background noise and prepulse) of +12, +16, and +20 dB. The lead interval (from prepulse onset to pulse onset) was 120 ms, and Temperament and Character Inventory was used in both groups. Significant correlations at SnR of +16 and +20 dB to ST were identified. Our results suggest that impaired sensorimotor gating, evaluated as lower PPI of ASR, of healthy subjects is correlated with self transcendence, the character which is closely related with schizophrenia and schizotypy. PMID- 22062873 TI - Cholesterol oxides in processed chicken muscle as influenced by dietary alpha tocopherol supplementation. AB - The effect of dietary alpha-tocopheryl acetate supplementation on the formation of cholesterol oxidation products (COPs) in chicken muscle during storage was investigated. Broiler chicks (Cobb 500 strain) were fed diets supplemented with 20, 200 or 800 mg alpha-tocopheryl acetate kg(-1) feed. Cooked breast and thigh muscle patties were prepared and stored at 4 degrees C for up to 12 days. Dietary supplementation significantly (p < 0.05) increased alpha-tocophenol concentrations in cooked muscle and decreased thiobarbituric acid-reacting substances (TBARS) during storage. COPs increased during storage. Total COPs ranged from 0.17-3.48 and 2.49-5.79 MUg g(-1) in breast and thigh meat, respectively. TBARS and total COPs were linearly correlated in breast (r = 0.68, p < 0.001,) and thigh patties (r = 0.75, p < 0.05). Dietary alpha-tocopheryl acetate supplementation significantly (p < 0.05) reduced the formation of COPs during storage. Total COPs formed after 12 days were reduced by 42 and 75% in breast, and 50 and 72% in thigh, at supplementation levels of 200 and 800 mg kg( 1) feed, respectively. PMID- 22062874 TI - Oxidation of controlled low-temperature vacuum dehydrated and freeze-dried beef and pork. AB - Processes of freeze-drying and controlled low-temperature vacuum dehydration were used for drying beef and pork. The drying-time of controlled low-temperature vacuum dehydration was less than that of freeze-drying. Monolayer moisture contents and surface areas of freeze-dried products were higher than those of products dried by controlled lowtemperature vacuum dehydration. The contents of myoglobin decreased and lipid oxidation increased during storage, and more marked effects were seen at higher storage temperatures. Myoglobin degradation in freeze dried beef and pork was greater than in samples dried by controlled low temperature vacuum dehydration. PMID- 22062875 TI - Electrical stunning in commercial rabbits: Effective currents, spontaneous physical activity and reflex behaviour. AB - Electrical stunning was evaluated in commercial slaughter rabbits. Different voltage applications with varying current duration were tested in recovery experiments in 71 animals. Stunning parameters and duration of insensibility were measured and analysed for assessing stunning effectiveness. A minimum stunning current of 140 mA which can be achieved with application of 100 V was recommended. PMID- 22062876 TI - Lipid and cholesterol oxidation in frozen stored pork, salame Milano and mortadella. AB - An investigation has been carried out on oxidative processes of fresh and stored frozen pork and of two pork products (salame Milano and mortadella). Wholesale pork cuts (shoulder, ham trimmings, belly and backfat) were checked fresh and after frozen storage (1, 3 and 6 months). The streaky bacon was studied fresh and after scalding at 80 degrees C. Salame Milano and mortadella were produced with fresh and frozen raw materials and a few commercial samples were also part of the study. No real differences have been observed between commercial and experimentally produced salame and mortadella. Peroxide and TBARS values were low in all cases. Among the cholesterol oxides determined (7beta-hydroxycholesterol, 5,6alpha-epoxycholesterol, 7-ketocholesterol and 25-hydroxycholesterol) those dangerous for human health were either absent or their concentration was below toxic levels. The results are discussed on the light of literature reports and Italian pork products technologies. PMID- 22062877 TI - Ultrasonic scanning measurements of the longissimus thoracis et lumborum muscle to predict carcass muscle content in sheep. AB - Nineteen Omani sheep (average 26 kg body weight) were scanned over the 6th rib, 12th rib and the second-last lumbar vertebra, to determine the maximum depth (B), circumference, area of the cross-section and volume of the longissimus thoracis et lumborum (LD) muscle. The volume of the muscle was estimated by multiplying the average area of its cross-section obtained at the three sites by its length. After slaughter, the LD muscle was dissected out, frozen, and its maximum depth, circumference, length, weight and volume were determined. Correlation and regression analyses were carried out to evaluate relationships between scanning and real measurements and between scanning measurements and carcass total muscle content. Generally there were positive correlations (r = 0.43-0.66) between the LD scanning measurements made at the 12th rib and the corresponding measurements made on the dissected muscle. The volume of the LD muscle estimated from scanning was positively correlated (r = 0.59) with its real volume which was correlated with its weight (r = 0.51) and consequently with the total carcass muscle content (r = 0.69). Ultrasonic scanning can be used to predict the circumference and volume of the LD muscle. These may be used for prediction of total carcass muscle content in sheep in addition to traditional measurements of the muscle (the maximum depth B) and area. PMID- 22062878 TI - Determination of endpoint temperatures in previously heat treated beef using reflectance spectroscopy. AB - Heat processing endpoint temperature affects several quality parameters of meat. The present paper focuses on using near-infrared and visual light reflectance spectroscopy at 400-2500 nm to determine the endpoint temperature in previously heated ground beef. Glass fibre filters with beef juice centrifuged from m. longissimus lumborum were used as samples for the technique Dry Extract Spectroscopy by Infrared Reflection (DESIR). Combined with multivariate analysis, this method gave prediction errors down to +/- 0.74 degrees C in the temperature range 65.6-75.6 degrees C, showing that DESIR is a potential screening method. The dominant part of the predictive information was in the visual part of the spectra. PMID- 22062879 TI - Effect of growth path on the tenderness of the semitendinosus muscle of Brahman cross steers. AB - The growth paths of 36, nine-month-old Brahman-cross steers were modified to determine the effect of their growth history on tenderness of the semitendinosus (ST) muscle. Steers were assigned to one of three treatment groups. One group of steers (uninterrupted group) was grazed on improved tropical pasture for 257 days and had an average weight gain of 0.6 kg day(-1). The other two groups were fed a restricted diet of low-quality grass hay and lost on average ~ 13% of their initial live weight over 100 days. These groups were then regrown for 157 days on either pasture (pasture finished) with the uninterrupted group, or on a grain based feedlot diet (grain finished). Growth rates of the previously restricted groups during the regrowth phase were indicative of compensatory growth and were significantly different (p < 0.05) at 0.76 (sem 0.03) kg day(-1) and 1.22 (0.05) kg day(-1), pasture and grain finished groups, respectively. Growth rates for both restricted groups were significantly different (p < 0.05) from the uninterrupted group [0.55 (0.02) kg day(-1)]. At slaughter, the grain finished group had heavier carcases, higher dressing percentages and more fat coverage, than either the uninterrupted or pasture finished groups, the latter being significantly lighter than the uninterrupted group. Tenderness was assessed by shear, compression (C) and adhesion (ADH) measurements. Shear peak force (PF) values of cooked ST samples did not differ significantly between groups. However, PF values of pressure-heat treated ST samples from the grain finished group were significantly less (p < 0.05) than comparable values from the uninterrupted group suggesting a reduced contribution of connective tissue to toughness. The pasture finished group mean PF value was not significantly different from either the uninterrupted group or grain finished group means. C and ADH values were significantly less (p < 0.05) in the grain finished group compared to the pasture finished groups values, again indicating a reduced connective tissue contribution to toughness. We conclude that the physical properties of the connective tissue component of the ST muscle may be altered by rapid compensatory growth after a weight loss phase and reduce the connective tissue contribution to toughness which may enhance meat tenderness. PMID- 22062880 TI - Shelf-life extension and colour stabilisation of beef packaged in a low O(2) atmosphere containing CO: Loin steaks and ground meat. AB - A combination of low O(2), high CO(2) and very low CO was investigated for packaging fresh beef steaks and ground meat. The following atmospheres were used: 70% O(2) + 20% CO(2) + 10% N(2) (CMA); 70% O(2) + 20% CO(2) + 9% N(2) + 1% CO (HO?CO) and 24% O(2) + 50% CO(2) + 25% N(2) + 1% CO (LO?CO). Bacterial counts showed that LO?CO atmosphere greatly reduced psychrotrophic population, so that log cfu cm(-2) was under 7.5 at 29 days of storage at 1 degrees C. All the objective measurements related to meat colour (a(*), hue, Chroma and metmyoglobin concentration) revealed that the bright-red colour was more stable in both HO?CO and LO?CO atmospheres, reaching 29 days of storage without appreciable signs of oxidation. Sensory analysis confirmed these results. PMID- 22062881 TI - Measurement of nitric oxide and the effect of enhancing or inhibiting it on tenderness changes of meat. AB - Possible roles of the cellular messenger nitric oxide (NO) in post-mortem meat ageing were investigated in bull m. longissimus lumborum. Both enhancement and inhibition of NO activity had positive and negative effects, respectively, on early rates of ageing. These also correlated with direct measurements of NO in the meat samples. However, by 8 days of storage, the tenderness was not significantly different to non treated meat samples. PMID- 22062882 TI - Assessment of commercial lamb meat quality by British and Spanish taste panels. AB - Trained sensory panels in Britain and Spain assessed loin meat from commercial lambs purchased in Spain, which included Welsh lamb (imported from Britain) and two Spanish breeds (Merino and Rasa Aragonesa). The British panel also assessed British lamb purchased in local butcher shops and supermarkets. Sensory panels, in each country, received meat from the same lambs and used their local methods of cooking and assessment. Spanish panels used unstructured line scales to measure lamb odour intensity, tenderness, juiciness, lamb flavour intensity and two hedonic scales of flavour liking and overall liking. The British panel used 8 point category scales with the same attributes. Results from both panels in objective parameters were in agreement, hence showing that different trained sensory panels may arrive at the same conclusion. However, when panellists were allowed to make hedonic judgements (preference), the British panel preferred British lamb and the Spanish panel preferred Spanish lamb. This finding has important consequences for lamb producers who export their lambs and demonstrates that the underlying reasons for different preferences should be investigated. Production variables are discussed in relation to their influence on lamb eating quality and as a way to tailor lamb eating quality attributes familiar to consumers in the importing country. PMID- 22062883 TI - Influence of processing on adherence of a highly extended ham to its cooking bag. AB - Highly extended cook-in-the-bag hams (65% brine/meat), representative of the products currently manufactured in Canada for mass distribution, were prepared using standard industrial equipment. Adherence between the cooked product and its packaging film was evaluated by measuring the force required to peel an excised band of film from the product surface. Overall, film-product adherence did not change after two weeks of refrigerated storage and was not affected by the extent of tumbling (from 360 to 4500 total turns) or by the cooking cycle (constant temperature of 74 degrees C, constant temperature of 84 degrees C, or stepwise temperature increase, until core temperature reaches 69 degrees C). Adherence was considerably reduced, however, when the extended muscles were finely homogenized prior to stuffing. A more detailed analysis of the results suggested that the occasional lack of proper film-product adherence observed in industry during the manufacture of highly extended hams cannot be due to mere deviations from the regular tumbling or cooking cycles. In addition, results point to the necessity of seeking alternative methods to quantify adherence between meat products and their cooking bags. PMID- 22062884 TI - Sensory and technological meat quality in carriers and non-carriers of the RN(-) allele in Hampshire crosses and in purebred Yorkshire pigs. AB - The effect of the dominant RN(-) allele on technological and sensory meat quality of loin and ham from pigs, crossbred from Landrace * Yorkshire sows and one Hampshire sire heterozygous for the RN(-) allele was studied. The non-carriers of the RN(-) allele and the purebred Yorkshire pigs were similar regarding most of the technological traits. In comparison with the RN(-) carriers, they had higher values for pH(u), Napole yield, dry matter and protein content, but lower values for drip loss, filter paper wetness, cooking loss, internal reflectance, residual glycogen and glycolytic potential. The three groups did not differ concerning lactate content, intramuscular fat or ash content. Shear-force values did not differ between the two RN genotypes, but both genotypes had lower shear-force values than the purebred Yorkshire pigs. Non-carriers had higher processing yield for cured cooked ham than RN(-) carriers. The RN(-) allele had little effect on the sensory attributes, as assessed by a trained panel using a descriptive test, but there was a tendency to lower chewing time for meat from the crossbreds compared to the purebred Swedish Yorkshire. RN(-) carriers produced more acidic fresh loin than non-carriers and purebred Yorkshire pigs, and juicier cured cooked ham than non-carriers. PMID- 22062885 TI - Effect of calcium chloride marination on calpain and quality characteristics of meat from chicken, horse, cattle and rabbit. AB - Differences in the quality of meat obtained from four animal species (beef, horse, rabbit and chicken) treated with two concentrations of calcium chloride (75 or 150 mM) were evaluated by a sensory panel. Physicochemical variables analysed were water holding capacity, instrumental colour and pH. Sensory analysis was by recognition index (R-index) by untrained and trained panels. CaCl(2) led to an increase in enzymatic activity, although it was not significantly different in treated compared to untreated samples. Lightness was higher (paler) in treated meat for all species studied. R-index showed that treatment of raw beef with 75mM CaCl(2) had negligible effect on odour compared to fresh, untreated beef. More juicy meat resulted from marination. Treatments with 150 mM CaCl(2) caused a more tender meat. The best combinations of cooking method and CaCl(2) concentration to obtain the most acceptable meat varied from attribute to attribute. The best odour was obtained when beef was treated with 150 mM CaCl(2) and cooked in a convection oven, whereas juiciness was improved if beef was treated with 150 mM CaCl(2) and cooked in a microwave oven. The highest scores for tenderness were for 75 mM CaCl(2)-treated samples regardless of cooking method. Flavour profile showed that the most marked feature in marinated beef is the predominance of a bitter flavour and after taste, which probably masks other flavour attributes. It is concluded that, in accordance with other authors, marination has no adverse effects on beef odour and improves texture, producing more tender material. However, marination at the CaCl(2) levels tested caused a bitter after taste and flavour. PMID- 22062886 TI - Heat-induced gelation properties of chicken breast muscle salt soluble proteins when mixed with beta-lactoglobulin or an alpha-lactalbumin enriched protein fraction. AB - The heat-induced gelation properties of mixed protein systems containing chicken breast muscle salt-soluble proteins (SSP) and beta-lactoglobulin (beta-lg) or SSP and an alpha-lactalbumin-enriched fraction (alpha-la) in 0.6 M NaCl, pH 6.5, were investigated using dynamic rheology. At 70 degrees C, SSP had greater storage modulus (G') values than mixtures containing SSP/alpha-lg. However, at 90 degrees C, mixtures containing 80:20 and 60:40 SSP: beta-lg had higher G' values than SSP alone, indicating that denaturation of beta-lg directly or indirectly facilitates the formation of a more rigid gel structure. On subsequent cooling to 20 degrees C, the extent of structure formation, as reflected by G' values, was greater for SSP than for mixtures containing SSP/beta-lg, which suggests that the denatured beta-lg is unable to interact with the SSP during cooling. Mixtures containing SSP and an alpha-la-enriched fraction had lower G' values than SSP at 90 degrees C and on subsequent cooling to 20 degrees C, which reflects the poor gelling properties of alpha-la. A fibrous network was observed when the microstructure of the SSP and 40:60 SSP: alpha-la gels were examined using scanning electron microscopy, while aggregated networks were seen in the beta-lg and 40:60 SSP: beta-lg gels. No significant differences (p > 0.05) were observed between the water holding capacity (WHC) of SSP and SSP/beta-lg gels. Gels formed from a mixture of SSP and the alpha-la-enriched fraction had lower WHC than the SSP gels. The myosin heavy chain was a major contributor to gel structure formation in all mixed gel systems. PMID- 22062887 TI - Reduction in microbial load on buffalo meat by hot water dip treatment. AB - Buffalo meat cuts from shoulder and leg portions were subjected to hot water treatment (70 and 80 degrees C for 30 and 60 s). Meat cuts dipped in water at ambient temperature served as control. The surface samples were analysed for microbial load, visual score for colour and numerical values of colour parameters (a(*), b(*), L(*), W). Control samples of shoulder and leg meat had a mean total plate count (TPC) of 4.15 log CFU cm(-2) and 3.81 log CFU cm(-2) and enterobacteriaceae counts of 2.33 log CFU cm(-2) and 2.26 log CFU cm(-2), respectively. Treatment of meat cuts with hot water reduced the TPC significantly (p < 0.001)with a highest reduction of 1.60 log in leg meat and 1.80 log in shoulder meat at 80 degrees C. Hot water treatment of meat eliminated enterobacteriaceae. Although, there was discolouration of meat by hot water treatment, the colour regained during storage of meat at refrigerated temperature (4 +/-1 degrees C). Hot water treatment of meat resulted in loss of redness (a(*)), increase in lightness (L(*)) and whiteness (W). After storage, a(*) increased and L(*) and W decreased. The results suggested that the dip treatment with hot water reduces the initial bacterial load substantially and improves the microbiological quality of buffalo meat without causing any permanent discolouration. PMID- 22062888 TI - Influence of vitamin A on the quality of beef from the Tajima strain of Japanese Black cattle. AB - Influence of vitamin A on the beef quality of the Tajima strain of Japanese Black cattle was studied. Marbling scores were correlated with serum vitamin A concentrations just before slaughter (r = -0.38). The mean marbling score of the low vitamin A group that were not supplemented with vitamin A after 15 months of age was significantly higher than that of the group supplemented with high vitamin A. However, there was no significant difference in the marbling scores between the group that were not given vitamin A after 23 months of age and the high vitamin A supplemented group. These results suggest that vitamin A supplementation affects carcass marbling only if given before 23 months of age, in these cattle. PMID- 22062889 TI - Effects of fat level, tapioca starch and whey protein on frankfurters formulated with 5% and 12% fat. AB - The effects of fat level (5% and 12%), tapioca starch and whey protein on the hydration/ binding properties, colour, textural and sensory characteristics of frankfurters were investigated. Decreasing the fat content increased cook loss and decreased emulsion stability and product lightness. Fat reduction increased smoke, spice and salt intensities and increased overall flavour intensity and juiciness. Texture profile analysis (TPA) indicated that fat reduction decreased gumminess and cohesiveness but the other parameters measured were unaffected. Addition of tapioca starch or whey protein reduced cook loss and increased emulsion stability. Whey protein did not effect the sensory characteristics but tapioca starch increased overall flavour intensity. Both ingredients increased hardness, adhesiveness, gumminess and chewiness as measured by TPA. Two-factor interactions between fat level and ingredient were observed for several parameters. The results indicate that both ingredients can partially offset some of the changes which occur in low-fat frankfurters when fat is replaced with added water and protein level is constant. PMID- 22062890 TI - Effect of age at slaughter on chemical traits and sensory quality of Longissimus lumborum muscle in the rabbit. AB - The effect of age on chemical composition and sensory quality of longissimus lumborum muscle was investigated in rabbits slaughtered at 11 weeks or 18 weeks of age. Intramuscular fat (IMF) content increased from 1.3 to 2.2%, crude protein content ranged from 23.4-26.9%, whereas water content declined from 74.0 to 69.3%, as the age increased. The sensory quality was assessed by a 10-member experienced sensory panel. The age was found to affect meat tenderness, whereas juiciness and flavour did not differ significantly between ages. A positive trend was observed between tenderness and IMF content, both within age and between ages. Therefore, differences in sensory quality of rabbit meat were at least partly related to IMF content. PMID- 22062891 TI - Activation of the innate immune response and interferon signalling in myotonic dystrophy type 1 and type 2 cataracts. AB - Myotonic dystrophy (DM) is caused by a triplet repeat expansion in the non-coding region of either the DMPK (DM1) or CNBP (DM2) gene. Transcription of the expanded region causes accumulation of double-stranded RNA (dsRNA) in DM cells. We sought to determine how expression of triplet repeat RNA causes the varied phenotype typical of DM. Global transcription was measured in DM and non-DM cataract samples using Illumina Bead Arrays. DM samples were compared with non-DM samples and lists of differentially expressed genes (P<= 0.05) were prepared. Gene set enrichment analysis and the Interferome database were used to search for significant patterns of gene expression in DM cells. Expression of individual genes was measured using quantitative real-time polymerase chain reaction. DMPK and CNBP expression was confirmed in native lens cells showing that a toxic RNA gain of function mechanism could exist in lens. A high proportion, 83% in DM1 and 75% in DM2, of the significantly disregulated genes were shared by both forms of the disease, suggesting a common mechanism. The upregulated genes in DM1 and DM2 were highly enriched in both interferon-regulated genes (IRGs) and genes associated with the response to dsRNA and the innate immune response. The characteristic fingerprint of IRGs and the signalling pathways identified in lens cells support a role for dsRNA activation of the innate immune response in the pathology of DM. This new evidence forms the basis for a novel hypothesis to explain the complex mechanism of DM. PMID- 22062892 TI - Comparison between zotarolimus-eluting stents and first generation drug-eluting stents in the treatment of patients with acute ST-segment elevation myocardial infarction. AB - BACKGROUND: The purpose of this study was to compare the two year efficacy and safety of zotarolimus-eluting stents (ZES) and first-generation DES, sirolimus- (SES) and paclitaxel-eluting stents (PES), in an all-comer registry receiving primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 711 consecutive STEMI patients (ZES: 135, SES: 427, and PES: 149), who underwent primary PCI between January 2005 and June 2008 were enrolled from three centers. In our study, the efficacy analysis endpoint was target vessel failure (cardiac death, target vessel related myocardial infarction, and ischemia-driven target vessel revascularization) at 2 years. The safety analysis endpoint was a composite of all cause death, non-fatal myocardial infarction, and stent thrombosis within 2 years. RESULTS: At 2 years, the rates of target vessel failure in the ZES, SES, and PES groups were 14.8%, 12.9%, and 19.5%, respectively (p=0.141). The rates of composite safety endpoints at 2 years were not different among the three groups (ZES 8.1% vs. SES 13.1% vs. PES 16.8%, p=0.102). However, when comparing the two groups, ZES was safer than PES (adjusted HR 0.48, 95% CI 0.24-0.98, p=0.046). There was also a non significant trend in favor of ZES in the rate of stent thrombosis (ZES 1.5% vs. SES 2.3% vs. PES 4.7%, p=0.186). CONCLUSION: In the treatment of STEMI patients, ZES showed similar and acceptable efficacy compared to first-generation DES (SES and PES) up to 2 years. In addition, ZES seems to be more favorable than PES in terms of safety. PMID- 22062894 TI - Cardiopulmonary exercise testing for the assessment of exercise capacity in patients with cardiac syndrome X. PMID- 22062893 TI - Mononuclear cell adenosine deaminase and CD26/dipeptidylpeptidase-IV activities are sensitive markers of reperfusion during percutaneous transluminal angioplasty. AB - During ischaemia, the extracellular level of adenosine increases, which has cytotoxic effects. In endothelium, cell surface adenosine deaminase (ADA) complexing CD26 is coordinately induced during ischaemia as part of an adaptative response by eliminating adenosine. We examined whether a similar mechanism exists for mononuclear cells. We studied mononuclear cell surface ADA (MCADA) and dipeptidyl-peptidase IV activity (DPPIV) of membrane CD26 during percutaneous transluminal coronary angioplasty (PTCA) as a model of ischaemia-reperfusion. Enzymatic activities were compared with levels of ischaemia-modified albumin (IMA), a marker of ischaemia-reperfusion. METHODS AND RESULTS: Patients (15 men and 5 women) with non-ST segment elevation acute coronary syndrome related to a stenosis of proximal left anterior descending artery were prospectively included before revascularization. MCADA, DPPIV and IMA were measured before PTCA (T0) then 15 (T15) and 120 (T120) minutes after reperfusion. Fifteen healthy control subjects were enrolled. At T0, MCADA and IMA levels were higher in patients than in controls. MCADA decreased at T15 (median, IQR: 8.2 [7.6-9.8] IU) relative to T0 (11.25 [10-13.5] IU, p<0.01) and remained low at T120. DPPIV decreased at T15 (0.9 [0.7-1.1] AU) relative to T0 (1.05 [0.99-1.48] AU; p<0.01) and remained low at T120. IMA level increased only at T120. MCADA and DPPIV were correlated. Our findings are that MCADA and DPPIV decreased rapidly after angioplasty, suggesting that both catalysts are early markers of reperfusion. CONCLUSION: MCADA and DPPIV are sensitive and early markers of ischaemia-reperfusion process during PTCA. PMID- 22062895 TI - Ambulatory blood pressure is associated with subclinical atherosclerosis in spinal cord injury subjects. PMID- 22062896 TI - Night shift and impaired endothelial function: circadian out-of-synch may play a role. PMID- 22062897 TI - Improving in-hospital mortality in elderly patients after acute coronary syndrome -a nationwide analysis of 97,220 patients in Taiwan during 2004-2008. AB - BACKGROUND: Elderly patients seem to have especially poor outcomes after acquiring acute coronary syndrome (ACS). We conducted this study to examine the in-hospital mortality by utilization of invasive coronary therapies and age in a nationwide population in Taiwan. METHODS: This observational study was conducted on a retrospective cohort from January 2004 to December 2008. Epidemiological features, including incidence rate and clinical characteristics of ACS in a Chinese population were investigated. Risk factors of in-hospital mortality, including myocardial infarction, shock, previous history of stroke, chronic kidney disease, diabetes mellitus, congestive heart failure, pneumonia, chronic obstructive pulmonary disease, dementia, peripheral arterial occlusive disease, septicemia and the use of invasive coronary procedures, were explored using a logistic regression model. RESULTS: A total of 97,220 patients were enrolled, and 53.6% of them were elderly. A significant decrease in the utilization rate of invasive coronary therapies (diagnostic coronary angiography and PCI) and increased in-hospital mortality (p<0.001) were observed as patient age increased. Adjusted multivariate logistic regression analysis revealed that the impact of PCI in reducing in-hospital mortality is consistent across age groups, including those older than 75 years old. CONCLUSIONS: Our nationwide study provides evidence that PCI is associated with significant improvement of in-hospital mortality in patients with ACS. Even the very elderly patients could benefit from PCI. However, currently the utilization rate of PCI in the aging population still does not present enough. A prospective study is indicated to corroborate the findings of this study. PMID- 22062898 TI - Short-term effects of enhanced external counterpulsation on transthoracic coronary flow velocity and reserve in patients with coronary slow flow. PMID- 22062899 TI - Is a deceptive role of IGF-1 in Sirt1-PARP1 interactions the primary step of postnatal regression of hypertrophic cardiomyopathy in infants of diabetic mothers? PMID- 22062900 TI - Meat research in Argentina. PMID- 22062901 TI - Nutritional and eating quality of Argentinean beef: A review. AB - This review deals with distinctive aspects of quality of Argentinean beef in terms of tenderness, flavour, colour, juiciness, taste, acceptability, lipid content and composition and its resultant nutraceutical characteristics. Differences are due to beef production systems based on temperate or tropical grasslands aimed at shortening the fattening phase as far as possible, with limited or null use of concentrates. However, the effect of limited supplemental feeding is also discussed as well as the responses arising from the use of beef cattle genotypes, including British, Continental, Dairy, Zebu breeds and their crosses, adapted to the various environments and systems found in the country. PMID- 22062902 TI - A review of natural antioxidants and their effects on oxidative status, odor and quality of fresh beef produced in Argentina. AB - Meat derived from pasture feeding, is associated with a high level of antioxidants. Antioxidants are incorporated within cell membranes and protect tissues against oxidation from reactive oxygen species. This maintains the overall quality of meat and secondary products. This paper reviews the implications of incorporating natural antioxidants into fresh beef, focusing on the benefits of feeding cattle good quality pasture. Pasture samples typically have higher levels of alpha-tocopherol, beta-carotene, ascorbic acid and glutathione than feedlot samples. These compounds retard lipid and protein oxidation in fresh and stored meat, and preserve the color and odor quality of beef. The significance of antioxidant enzymes is variable, because their behavior depends on individual redox status before slaughter. Understanding total antioxidant activity requires information on antioxidant and pro-oxidant status. With an abundance of pasture, Argentina has a natural advantage in producing meat with a high antioxidant value. PMID- 22062903 TI - Meat quality of Argentinean "Camperos" chicken enhanced in omega-3 and omega-9 fatty acids. AB - Five diets were assessed with the aim of increasing oleic fatty acid and omega-3 polyunsaturated fatty acid content in 'campero' poultry meat and evaluating their influence on sensory attributes. Animals from treatment 1 (T1) were confined and fed with corn/soybean diet; in T2, animals were fed with a corn/soybean mix with free access to pasture; T3 diet had high oleic sunflower seeds (HOSS) and linseeds with access to pasture; T4 diet was similar to T2 with free access to chicory instead of pasture and T5 diet was similar to T3 with free access to chicory instead of pasture. Linseeds and HOSS supplementation significantly increased the fatty acids profile, regardless of forage supply. T3 MUFA content was significantly higher than in the other treatments. Due to the high presence of omega-3 PUFA in linseeds and HOSS treatments (T3 and T5), meat omega-6/omega-3 ratio decreased from 9 to 4. The presence of off-flavours was not influenced by diets but there was an interaction between portion and storage conditions. 'Poultry meat' aroma was only influenced by the storage conditions, being slight after 4 months of freezing, while presence of off-aromas was affected by diets. We conclude that it is possible to produce 'campero' poultry meat with enhanced omega-3 and omega-9 content and a low omega-6/omega-3 ratio using diets based on linseed and HOSS, without any important change in sensory properties. PMID- 22062904 TI - Oxidative stability and its relationship with natural antioxidants during refrigerated retail display of beef produced in Argentina. AB - The objective of this study was to determine if pasture or grain diets affect oxidative/antioxidative status and the color stability of beef during retail display. Ten crossbreed steers were fed on pasture. Five of them were randomly assigned to remain on this diet, and the other five were finished on feedlot system (grain diet) during 110days until slaughter. Slices of Psoas major steaks were randomly distributed among retail display times (1, 3, 5, 7 and 9days). Lipid and protein oxidation were higher in Psoas major steaks from grain diet than in pasture diet (P<0.05). After 3days of display, lipid oxidation increased in meat from grain diet, whereas in meat from pasture diet the first evidence was after 7days (P<0.05). Protein oxidation was higher in meat from grain diet than in meat from pasture diet at day 9 of display (1.15+/-0.92 vs. 1.91+/-0.70MUg/g, respectively; P<0.05). Antioxidant vitamins, alpha-tocopherol and beta-carotene were higher at time=0 in pasture Psoas major steaks (P<0.05) and were differentially reduced throughout storage. While alpha-tocopherol decreased 41% and 57% for pasture and grain beef respectively (P<0.05), beta-carotene levels remained practically unaffected in grain beef. After 7days of display "a" value was higher for Psoas major steaks from pasture diet (P<0.05). Besides, "L" parameter showed higher values for samples from grain diets but it was no affected by display time. No differences were observed between both treatments for "b" value, but a significant decrease (P<0.05) was observed along storage. Superoxide dismutase and catalase activity was stable throughout storage, while glutathione peroxidase activity decreased significantly (P<0.05). The results in this study demonstrated that the higher initial level and synergistic action (under light and air) of alpha-tocopherol and beta-carotene found in pasture finished animals improved the oxidative and color stability of beef, as showed by a better retention of redness at the end of retail display. PMID- 22062905 TI - Carcass characteristics of Neuquen Criollo kids in Patagonia region, Argentina. AB - Carcass characteristics of 336 kids from the Neuquen Criollo breed were evaluated. Two categories were taken into account: three months and 5 to 7 months kids. Live weight, carcass weights, measurement and indexes of 304 kids were calculated in a study done in a commercial slaughterhouse located in Chos Malal town. Thirty two carcass left sides were dissected into the major components: muscle, bone, fat and remaining tissues. Three months kids were compared with 5 to 7 months kids. The slaughter live weight of the former was 16.3kg and the latter was 22.4kg. Cold carcass weight and dressing percentage differed significantly (p<0.001) between age categories. Three months kids had a higher percentage of bones (26.8 vs. 21.7%; p<0.001) and a lower percentage of fat (10.8 vs. 15%; p<0.01) than those at 5-7 months, but both had similar percentages of muscle (56.4 vs. 57%; p=NS). There were significant differences in the percentages of primal carcass cuts: hind leg (32 vs. 34%; p<0.001), shoulder (22 vs. 20%; p<0.001) and neck, (10 vs. 8%; p<0.01) for three months vs. 5-7 months old kids, respectively. PMID- 22062906 TI - Meat quality traits of commercial hybrid pigs in Argentina. AB - This report describes the meat quality of two INTA hybrids (hybrid females) sired by Duroc (D) or Yorkshire (Y) boars and a third one from PIC (S), a cross of females C22 to 412 boars. Starting at 30kg live weight, 18 barrows and 18 gilts of each genotype were kept in identical conditions until slaughtered at 110kg. Longissimus dorsi muscles were analyzed. Means differed significantly (P<0.05) for drip loss (higher in S); tenderness (more tender in D), water holding capacity (higher in Y); cooking loss (higher in Y); colour parameter L(*) (lower in D) and b(*) (higher in S) and intramuscular fat content (higher in D). As a result of sensory analysis, it was found that D was the most tender and juicy. There were few sex effects and no genotype-sex interactions. Distinct differences in meat quality between hybrids do exist, with D superior, S the worst, and Y intermediate. PMID- 22062907 TI - Diet and genotype effects on the quality index of beef produced in the Argentine Pampeana region. AB - Steers of varying genotypes (Aberdeen Angus, Charolais x AA and Argentine Holstein) in four feeding systems were evaluated. Feeding systems were: S1=a diet based on pastures only; S2=a similar forage base as S1 plus a daily supplementation with cracked corn, at 0.7% of l.w./head/day; S3=a similar forage base as S1 plus a daily supplementation with cracked corn, at 1.0% of l.w./head/day; and S4=a regular feedlot diet. Tenderness and marbling were not affected by the feeding system. Feedlot meat showed an n-6/n-3 ratio significantly higher than meat produced with the diets based on pastures (S1=2.1; S2=3.1; S3=4.5; S4=14.2) (P<0.05), whereas CLA content had an inverse behavior, showing S1 (0.67%) and S2 (0.64%) higher concentrations than S3 (0.55%) and S4 (0.28%) (P<0.05). Diet based on pastures plus a low level of supplementation produced meat with better nutritional characteristics than other productive alternatives, without significant effects of the biotypes. PMID- 22062908 TI - Effect of salt addition on sous vide cooked whole beef muscles from Argentina. AB - Sodium chloride (NaCl, 0-1.4%) and sodium tripolyphosphate (STPP, 0-0.5%) were added to Semitendinosus muscles and submitted to sous vide cooking at different temperatures (55-75 degrees C). The effects of these three factors on pH, cooking loss, instrumental colour parameters, protein solubilization and distribution, and micro- and ultra-structure were evaluated. Quadratic surface responses equations were obtained from data (pH, cooking loss and colour parameters) as a function of the salts concentrations and cooking temperature. Both salts - alone or in combination - successfully reduced cooking loss. The best results were obtained for the combinations 0.25%STPP+1.20%NaCl and 0.25%STPP+0.70%NaCl, and temperatures between 60 and 65 degrees C. Under these conditions, cooking loss was reduced close to 0%. pH was only dependent on STPP concentration, with a threshold concentration value of 0.25%. Temperature increment and NaCl addition produced a redness reduction. STPP incorporation recovered partially this parameter in comparison to non-added samples. Microscopy and SDS-PAGE results support the effect of the selected combinations of factors, suggesting that both salts together induced protein solubilization and gelation upon heating. PMID- 22062909 TI - A review of bacteriocinogenic lactic acid bacteria used as bioprotective cultures in fresh meat produced in Argentina. AB - Several lactic acid bacteria (LAB) associated with meat products are important natural bacteriocin producers. Bacteriocins are proteinaceous antagonistic substances that are important in the control of spoilage and pathogenic microorganisms. The use of LAB as bioprotective cultures to extend the shelf life of fresh meat can improve microbial stability and safety in commercial meat preservation. Lactobacillus curvatus CRL705 used as a protective culture in fresh beef is effective in inhibiting Listeria innocua and Brochothrix thermosphacta as well as the indigenous contaminant LAB, retaining its inhibitory effect at low temperatures and having a negligible effect on meat pH. In addition to the hurdle represented by low temperature and vacuum-packaging, the use of live cells of Lb. curvatus CRL705 seems more feasible from an economic point of view - and without legal restrictions - compared to the addition of purified bacteriocins. A description of meat-borne bacteriocins and their application in meat to extend shelf life is discussed. PMID- 22062910 TI - Beef lipids in relation to animal breed and nutrition in Argentina. AB - Fatty acid (FA) composition of intramuscular fat (IMF) in M. Longissimus dorsi (LD) was measured in 72 steers from Angus (A), Charolais*Angus (CHA*A) and Holstein Argentine (HA) breeds. The steers were allotted to four dietary treatments of six animals each: T1, steers grazed on pasture; T2, steers supplemented with cracked corn grain (0.7% of live-weight) daily and free access to pasture; T3, steers supplemented with cracked corn grain (1% of live-weight) daily and free access to pasture; and T4, feedlot (concentrate based on corn, alfalfa hay and soybean meal without access to pasture). At slaughter weight, samples of LD at the 11th rib were used for intramuscular lipid analysis. The diet was shown to be more important than breed in determining FA composition. Pasture beef had higher percentages of saturated fatty acids (SFA), n-3 polyunsaturated fatty acids (PUFA) and conjugated linoleic acid (CLA) and lower percentages of IMF, monounsaturated fatty acids (MUFA), n-6 PUFA and n-6/n-3 ratios than feedlot beef. HA beef presented lower percentages of SFA and more MUFA with a higher n-6/n-3 ratio than A and CHA*A. Comparing grass and feedlot beef the amounts of FA in muscle (mg/100g) were, respectively 18:3 n-3 (44 vs. 11mg), CLA (20 vs. 12mg), 20:5 n-3 (20 vs. 11mg), 22:5 n-5 (20 vs. 11mg), 22:6 n 3 (12 vs. 6mg) and n-3 PUFA (84 vs. 32mg). Feedlot beef has more SFA (1372 vs. 1081mg), MUFA (1574 vs. 1078mg), PUFA (350 vs. 227mg) and n-6 PUFA (318 vs.143mg). PMID- 22062911 TI - Mathematical modelling of microbial growth in ground beef from Argentina. Effect of lactic acid addition, temperature and packaging film. AB - The effects of: (i) storage temperature (0, 4 and 10 degrees C), (ii) gaseous permeability of the packaging film (polyethylene and EVA SARAN EVA for vacuum packaging), and (iii) natural beef pH (5.6, 5.8 and 6.1) on the growth of different bacteria isolated from beef muscle were examined. The bacteria were Klebsiella, Pseudomonas sp. and Escherichia coli. Microbial growth was modelled using Gompertz and linear equations. The effects of temperature on microbial growth rate (MU) and on lag phase duration were modelled using an Arrhenius type equation. In polyethylene, E. coli was the microorganism, that showed the highest MU values and also the greatest effect of pH on MU, especially in samples stored at 4 and 10 degrees C. In the case of Klebsiella sp., neither pH nor temperature had marked effects on MU and on LPD. In ESE film, MU of all the microorganisms were less affected by pH and temperature than in polyethylene. In ESE film E. coli showed the highest effect of pH on MU, at 4 and 10 degrees C. LPD increased significantly with respect to the values in polyethylene, with Klebsiella sp., showing the highest values of LPD, followed by E. coli. Experiments in ground beef with added lactic acid producing a decrease of the original muscle pH from 6.1 to 5.6 showed that the kinetic parameters of the microbial flora did not differ significantly from those of beef samples in which the original pH was 5.6. PMID- 22062912 TI - Animal performance and meat quality in cull cows with early weaned calves in Argentina. AB - Early weaning of calves (60 days old) is adopted in cow-calf operations for its high reproductive response. The objective of this research work was to find how age classes are related to beef quality in early weaning cull cows. Twenty four cows were grouped in four different age classes (teeth and number of calves produced) from two teeth and no calf produced, up to 12 years and 7 calves produced. All cows grazed a perennial pasture based on alfalfa and fescue. There were differences (P<0.05) in final weight (younger cows being lighter) but no other differences could be found during field conditions or in abattoir data (carcass weight and yield, top value hindquarter cuts weight and carcass percent). No differences (P>0.05) could be found in meat quality attributes except for moisture, protein and fat yellowness. Differences (P<0.05) in sensory attributes could only be found in connective tissue. PMID- 22062913 TI - Effect of aging on the characteristics of meat from water buffalo grown in the Delta del Parana region of Argentina. AB - Fifteen crossbreed water buffalos were selected from a farm in Delta del Parana, Entre Rios Province, Argentina. Animals were castrated males 20-24 months old reaching final live weights of 400-420kg. They were predominantly of Mediterranean and Murrah breeds and were feed in naturally grown pastures. Tenderness and chewiness increased with postmortem aging (p<0.05). Aging did not affect flavour and odour scores, even though certain off-flavours and off-odours were reported. Changes in colour with aging were similar to those seen in beef. PMID- 22062914 TI - The source and market development of a premium product - Beef from the Argentine Pampas. AB - The two main features of beef from the Argentine Pampas are its quality and geographical origin. In addition to the normal aspects of meat quality detected by sensory panels or measured by scientific instruments, the quality of Pampean beef includes the powerful symbolic quality of pampas life - the immensity of the green grasslands and the culture of the gaucho, living on horseback or sipping mate while making an asado (barbecue). This review defines the qualities and geographical origin of Pampean beef, and explains their interrelationships in terms of animal breed, nutrition and production systems. The objective is to help secure Pampean beef against unfair encroachment from competing products which lack the true authenticity of beef from the Argentine Pampas. PMID- 22062915 TI - Conjugated linoleic acid (CLA) and polyunsaturated fatty acids in muscle lipids of lambs from the Patagonian area of Argentina. AB - The concentrations of fatty acids were measured in total lipids, triacyglycerol and phospholipid fractions of intramuscular fat (IMF) from the Longissimus dorsi (LD) muscle of 10 lambs reared to approximately 30kg live weight on natural pasture with their dams. Fatty acid composition was also measured in 25 (five of each) Semitendinosus (ST), Semimembranosus (SM), Rectus femoris (RF), Gluteus (GLU) and Tensor fascia latea (TFL) muscles. Intramuscular fat percentages were similar for all muscles. Aspects of the fatty-acid patterns of relevance to human nutrition tended to favor the leg muscles with lower saturated fatty acids (SFA %), n-6/n-3 fatty acid ratios (p<0.01) and higher concentrations of the conjugated linoleic acid (CLA) (p<0.05). The estimated fatty acid concentrations (mg/100g of meat) showed higher contribution of arachidonic (C20:4 n-6), eicosapentanoic (C20:5 n-3), docosapentanoic (C22:5 n-3) and docosahexanoic (C22:6 n-3) acids in leg compared to LD lipids. PMID- 22062916 TI - Effect of salt addition on the thermal behavior of proteins of bovine meat from Argentina. AB - Research was undertaken to investigate how the addition of sodium chloride (NaCl) and/or sodium tripolyphosphate (TPP) to sous vide cooked meat pieces produces an increase in water holding capacity (WHC). Semitendinosus muscles were injected to obtain tissue final concentrations of 0.70% NaCl, 0.25% TPP, 0.70% NaCl+0.25% TPP, and 1.20% NaCl+0.25% TPP. SDS-PAGE analysis showed increased protein solubilization in those treatments which included NaCl. Thermal analysis of whole muscles and isolated myofibrils showed the destabilizing effect of NaCl and a global stabilizing effect of TPP. Both salts together induced a destabilizing global effect, where TPP assisted NaCl in breaking the meat structure. It is suggested that the WHC increments are related to conformational changes in myofibrillar proteins and to the weakening of myofibrillar structure by the removal of myofibrillar proteins. PMID- 22062917 TI - Optimization of whey protein concentrate and sodium chloride concentrations and cooking temperature of sous vide cooked whole-muscle beef from Argentina. AB - Response surface methodology was used to optimize the effect of cooking temperature (CT: 65-75 degrees C) and the incorporation of whey protein concentrate (WPC: 0-3.5%) and sodium chloride (NaCl: 0-2.5%) on technological, physical and sensory characteristics of cooked whole-muscle beef. Post-injection weight loss diminished when NaCl concentration increased. Moreover, the increment of both additives produced a reduction of cooking loss. An opposite effect was observed with the increment of CT. As it was expected, a total yield improvement was achieved by increasing both ingredients and diminishing CT. Equivalent yields are achieved complementing both ingredients, meaning that if one ingredient concentration is reduced the other has to be increased. Shear force values were not affected by the studied factors. Instead, lightness was reduced by their increment. At 65 degrees C, injected muscles had lower flavour and odour scores than control. At all CT analyzed, the incorporated brines improved juiciness and tenderness-related attributes. Present results recommend the use of a CT of 70 degrees C and maxima WPC and NaCl concentrations of 2.6% and 1.9%, respectively. PMID- 22062918 TI - Effect of whey protein concentrate and sodium chloride concentrations on the odour profile of sous vide cooked whole-muscle beef from Argentina. AB - Semitendinosus muscles added with whey protein concentrate (WPC) and sodium chloride (NaCl) were submitted to sous vide cooking. Four enhancement treatments and a control were tested: 0.875% WPC (w/w)+0.625% NaCl, 2.625% WPC+0.625% NaCl, 0.875% WPC+1.875% NaCl, 2.625% WPC+1.875% NaCl, and control (non-injected muscles). Odour analyses were carried out with an electronic nose (EN) system. EN data were evaluated applying Principal Component Analysis, Linear Discriminant Analysis and Partial Least Squares algorithm. EN was able to discriminate the odour profiles of cooked enhanced beef as a function of the amount of WPC added. No significant differences in odour profiles were observed regarding NaCl concentration. These results agreed with those obtained when odour profiles were analysed in WPC dispersions. The reported results support the applicability of EN methodology for analysing the impact of processing parameters on beef odour profiles. PMID- 22062919 TI - Meat quality of lambs produced in the Mesopotamia region of Argentina finished on different diets. AB - The meat quality of Corriedale lambs (40kg live weight) produced in the Mesopotamia region (Argentina) was assessed. These lambs had different finishing diets: only native grass pasture, ground alfalfa and alfalfa-linseed pellet (70/30). Carcass yield, longissimus dorsi area, backfat thickness, marbling, pH, meat and subcutaneous fat color, cooking loss, Warner-Bratzler shear force, fat, protein and moisture content were determined. Lambs finished on alfalfa-linseed pellet had the highest carcasses yield and backfat thickness and their meat had a lighter color (higher L(*) value), higher marbling and tenderness than meat from lambs reared on native grass pasture. Grass-based finishing can lead to the production of leaner meat, with a more reddish color (higher a(*) value). The ground alfalfa finishing diet seems to be intermediate between native grass pasture and alfalfa-linseed pellet with respect to carcass yield, backfat and meat color. In addition, the animals fed on ground alfalfa showed the highest muscle area. PMID- 22062920 TI - Antioxidant consumption and development of oxidation during ageing of buffalo meat produced in Argentina. AB - Buffalo meat production is increasing in Argentina. Information on meat quality and nutritional value will be useful in marketing. This work describes the oxidative stability of the Longissimus dorsi (LD) in relation to consumption of antioxidant vitamins, fatty acid composition and color deterioration during ageing. Vitamins levels found in fresh beef were 4.22+/-0.93; 0.24+/-0.05 and 0.25+/-0.06MUg/g for alpha- and gamma-tocopherol, and beta-carotene, respectively. Vitamin loss was almost 90% throughout an ageing period of 25 days at 2 degrees C. Concomitantly, TBARS levels increased from 0.076+/-0.018 to 0.14 6+/-0.032mg MDA/kg beef. Hexanal and pentanal levels were low and no correlations with oxidation were detected (P>0.05). The predominant color changes in aged beef were reduced redness and yellowness with an increase in lightness (P<0.05). Vitamin levels and TBARS were used to develop a prediction equation for post mortem aging. PMID- 22062921 TI - Stress relaxation characteristics of low-fat chicken sausages made in Argentina. AB - Low-fat sausages were prepared with fresh chicken breast meat and formulated with different levels of added fat, whey protein concentrate, and hydrocolloids (xanthan and guar gums) to study the effect of composition on the stress relaxation behavior of the products. Stress relaxation experiments were conducted on precooked sausages at 25 degrees C. Generalized Maxwell and empirical Peleg models were used to predict the stress relaxation behavior of the material. A model with seven maxwellian elements in parallel with a pure elastic element showed a very good agreement with experimental data. Results show that the proposed model satisfactorily fits the experimental data better than Peleg's model or Maxwell models with less elements. The relaxation time distribution functions were obtained. The characteristic relaxation time was shorter (2500s) for the formulations with no added fat which produced a less elastic product while the sausages with added fat showed longer characteristic relaxation time (5000s). The stress relaxation experiment differentiated the viscoelastic nature of different formulations due to reduction of fat content. PMID- 22062922 TI - Modeling heat transfer and inactivation of Escherichia coli O157:H7 in precooked meat products in Argentina using the finite element method. AB - The presence of Escherichia coli is linked with sanitary deficiencies and undercooking of meat products. Recent studies have detected E. coli O157:H7 in black blood sausages. Minimum time-temperature specifications to kill the bacteria were obtained by numerical simulations of the microscopic heat conduction equation using the finite element method, and calculating the temperature profile of the sausage and the population of E. coli at the coldest point during heating. The model was validated by heating sausages in a water bath. The effects of heat transfer coefficients and water temperatures on the required time to achieve an inactivation value (IV) of 12(log) are reported. Macroscopic heat balances were simultaneously solved to consider the temperature drop in the water batch as a function of the ratio between the mass of thermally treated sausage and the heat capacity of the system. PMID- 22062923 TI - Lactobacillus role during conditioning of refrigerated and vacuum-packaged Argentinean meat. AB - The role of Lactobacillus strains with bioprotective and technological potential on raw beef during 15days of storage under vacuum at 7 degrees C was investigated. The assayed strains were able to grow on the meat, Lactobacillus curvatus CRL705 and Lactobacillus sakei 23K showing the highest competitiveness. A net increase of amino acids was determined in inoculated samples when compared to the control, this being maximal for Lactobacillus plantarum CRL681. Although an important endogenous activity of meat sarcoplasmic proteins was observed, the disappearance of protein bands and the generation of a new one were detected as a consequence of Lactobacillus growth. A synergistic effect of Lactobacillus in combination with the muscle proteolytic enzyme complex can be suggested. From the studied strains, the bacteriocin producer L. curvatus CRL705 may be considered as a good candidate to contribute to meat ageing by means of small peptides and free amino acids generation while improving shelf life. PMID- 22062924 TI - Prediction of lean meat content in pork carcasses using the Hennessy Grading Probe and the Fat-O-Meater in Argentina. AB - Rapid evolution of pork production in Argentina requires new calibrations for predicting carcass lean meat percentage with the Fat-O-Meater (FOM) and Hennessy Grading Probe (HGP), first adopted in 1995. The second objective was to unify the lean percentage units with those applied by the European Union. Carcasses of 59 gilts and 56 barrows from different environments and breeds were tested. Carcass weights were from 65 to 117kg, and lean content was from 38% to 62%. Predicting lean content by multiple regression equations, the coefficients of determination R(2) were 0.801 and 0.794 for the FOM and HGP equations, and the residual standard deviations (RSD) were 2.40% and 2.45%, respectively. Both instruments had the same precision and were accurate enough to be adopted in national carcass grading classification. Hot carcass weight was not selected as a significant variable. The same prediction equations could be used for gilts and barrows. Quadratic terms did not improve predictions. PMID- 22062925 TI - Functional imaging in predicting response to antineoplastic agents and molecular targeted therapies in lung cancer: a review of existing evidence. AB - The increasing use of FDG-PET ((18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography) imaging in the staging of non-small-cell lung cancer (NSCLC) may result in a significant shift in stage distribution, with an increased percentage of patients staged as having metastatic disease and consequently a higher percentage of patients treated with systemic therapy. The amount of FDG-PET uptake in primary lung lesions has been shown to be correlated with tumour growth rate. Data suggest that tumours with increased glucose uptake are presumably more metabolically active and more biologically aggressive, and standardized uptake value (SUV) at PET may be regarded as a prognostic factor. Growing evidence suggests that PET may be used as a predictive marker to assess the activity of antineoplastic agents, allowing close monitoring of the efficacy of the treatment in order to be able to switch earlier to alternative therapies according to the individual chemosensitivity of the tumour. Currently the value of FDG-PET for monitoring response is complicated by the heterogeneity of the published data on the methods used for FDG quantification and the selection of the primary targets and clinical endpoints. As a result, objective validation of proposed thresholds of responsiveness is lacking. This article discusses the assessment of treatment response in NSCLC patients using functional imaging, and emphasizes advantages and limitations in clinical management. PMID- 22062926 TI - Electrophoretic separation of bovine muscle myosin heavy chain isoforms. AB - This study concerns the definition of the optimum conditions for separation of adult and developmental myosin heavy chain (MHC) isoforms in bovine muscle. The various techniques published do not result in good separation of the MHC in this species. The trials carried out concerned the concentration of acrylamide and N, N'-methylene-bis-acrylamide, and more particularly the concentration of Tris in the separating gel. The finding was that analysis of adult isoforms and developmental isoforms require different conditions. A acrylamide gradient of 3.5 10% with 200 mM Tris pH 8.8 gives good resolution for adult isoforms. Under these conditions 3 fast adult isoforms are revealed. However, study of MHC isoforms throughout foetal life in bovines is complex, and requires the combined use of more than one gel (gradient 3.5-10% at 200 mM Tris and gradient 3.5-10% at 250 mM Tris). PMID- 22062927 TI - Structural and functional characteristics of muscle fibres in pigs with different malignant hyperthermia susceptibility (MHS) and different meat quality. AB - In pigs, intensive growth of the musculature is often accompanied by malignant hyperthermia susceptibility (MHS; n gene) and poorer meat quality. Using histological and histochemical methods, different fibre characteristics in the Longissimus muscle were found in Pietrain*German Landrace pigs with this gene defect. Compared to MHS homozygous negative pigs, groups with the n gene had increased diameters of the mean fibre types and increased glycolytic metabolic potential, as shown by a higher frequency of the fast twitch glycolytic type and a lower frequency of the slow twitch oxidative fibre type. Differences between the groups were also found in the number of angular and giant fibre types. Furthermore, a positive correlation was found between the frequency of oxidative fibres and the relative enzyme activity of NADH tetrazolium reductase. The changes correlated with lower pH and higher drip loss in meat from the MHS homozygous positive group. In conclusion, the different muscle fibre characteristics can be interpreted as endogenous factors which influence the physiological condition in the muscle of the live animal and meat quality post mortem. PMID- 22062928 TI - Image texture features as indicators of beef tenderness. AB - Image processing techniques were developed to predict cooked-beef tenderness from fresh-beef image characteristics. Cattle from different finishing treatments were processed in a commercial plant. Two short loin steaks were sampled from each carcass; one used for sensory evaluation and the other for imaging. The samples varied significantly in both US quality grades and sensory tenderness scores. Color, marbling and texture features were extracted from the beef images. Statistical and neural network analyses were performed to relate the image features to sensory tenderness scores. Image texture features were found to be useful indicators of beef tenderness. Partial least squares and neural network models were able to predict beef tenderness from color, marbling and image texture features to R(2)-values up to 0.70. PMID- 22062929 TI - Sodium lactate and storage temperature effects on shelf life of vacuum packaged beef top rounds. AB - Cooked, vacuum-packaged beef top rounds containing up to 4% sodium lactate (NaL) in the final product were stored at 0, 4, 10 or 16 degrees C for 1, 7, 14 or 21 days. Aerobic plate counts (APCs) were lower for roasts containing 3 or 4% NaL and stored at 10 degrees C for 7 days. At higher temperatures and longer storage times, only those treated with 4% NaL were lower than controls. Lipid oxidation, Hunter L* and b* values decreased and Hunter a* values, cooked yields and Ph increased with NaL addition. Beefy odor decreased with storage but was higher in roasts containing NaL. Roasts with added NaL had lower rancid odor scores. PMID- 22062930 TI - The use of elastography to measure quality characteristics of pork semimembranosus muscle. AB - The objectives of this study were to determine if ultrasonic strain image analysis could estimate pork eating quality parameters (such as fresh color, drip loss, and Warner/Bratzler shear). Intact semimembranosus (SM) muscles (cap off) were analyzed for ultimate pH (pH(ult)). Forty-five SM muscles were selected from the larger allotment of fresh hams over a 3-week period. The SM muscles were selected based on high and low pH(ult) in an attempt to represent a wide range of pork quality. Ultrasonic strain images were obtained perpendicular to the SM muscle fibers of an 8-cm cube. Radio-frequency data from each SM were obtained from a field-of-view (FOV) of 40*30 mm(2) and digitized for each compression step. Tissue displacements were computed for each compression step. Tissue strains were computed from displacement data located in the FOV representing areas of harder and softer muscle tissue and converted to gray scale images at 256 levels. Tissue irregularity of hardness and softness was measured using Fractal dimension and Haralicks parameters. Twenty-one Fractal dimension (FR) parameters, at two neighborhood distances (N), from each strain image and nine Haralick's (HAR) textural parameters (inter-pixel distance=1) were analyzed for each image. The variable FR4N4 had a -0.279 correlation with SM ultimate pH (p<0.10); FR6N8 correlated to WB shear force at 0.325 (p<0.05); and FR21N8 had a correlation coefficient of 0.364 with intramuscular fat (p<0.01). Linear regression equations generated from FRN and HAR parameters for intramuscular fat (R(2)=0.468), Warner/Bratzler shear (R(2)=0.360), and 30 h drip loss (R(2)=0.208). Although elastographic measurement was significantly correlated to shear (p<0.05), a better understanding of physical meat texture is necessary before elastography can be used to identify superior quality pork. PMID- 22062931 TI - Hot processing and grind size affect properties of cooked beef patties. AB - This study was conducted to further understand the role that hot processing and grind size exert on cooked beef patty tenderness and other properties. Low-fat (10%) hot-processed (HP) and cold-processed (CP) beef were ground either through a 0.32 or 0.40 cm plate. A 20% fat CP product was also manufactured through a 0.32 cm plate. HP patties had higher pH, shorter sarcomere lengths, higher tenderness scores (including greater number of smaller particles during chewing) lower shear force values, higher flavor scores, less well-done cooked color, longer cooking times and higher cooking yields than CP patties (p<0.01). The use of a 0.32 cm rather than a 0.40 cm plate improved tenderness properties, especially for HP patties. Other properties were not greatly influenced by grind size. Sensory evaluation and scanning imagery of patties suggested that the greater tenderness of hot processed patties may be due to the presence of smaller meat particles. Highly contracted muscle, providing resistance to grinding, could be responsible for the small meat particles. PMID- 22062932 TI - Utilization of soy protein isolate and konjac blends in a low-fat bologna (model system). AB - Low-fat bologna formulations (LFBMS, <2.0% fat) were manufactured in a model system with two levels (0.5 or 1%) of two konjac blends (KB; KSS=konjac flour/starch and KNC=konjac flour/carrageenan/starch), and three levels (0, 2.2, 4.4%, DWB) of prehydrated soy protein isolate (SPI) to replace 0, 2 and 4% of the meat protein, respectively. Compared to 0.5% KB, the 1% level reduced (p<0.05) protein solubility (PS), vacuum purge (VP, %) and texture profile analysis (TPA) hardness. LFBMS containing KNC had higher (p<0.05) cooking yields, TPA fracturability and shear stress, but lower (p<0.05) expressible moisture (EM), VP values and TPA cohesiveness than KSS. Replacement of 4% meat protein with SPI increased (p<0.05) pH and yellowness (b*), but decreased (p<0.05) redness (a*), PS, EM and most textural characteristics, whereas no differences (p>0.05) were observed between 0 and 2% of meat protein replacements with SPI for most characteristics. PMID- 22062933 TI - Influence of intramuscular fat content on the quality of pig meat - 1. Composition of the lipid fraction and sensory characteristics of m. longissimus lumborum. AB - The present study is part of a project which aimed to examine the influence of intramuscular fat (IMF) content on the sensory attributes and consumer acceptability of pork. Two experiments were conducted to evaluate the influence of IMF level on the composition of the lipid fraction and on the sensory qualities of muscle longissimus lumborum (LL). Each of these experiments used 32 castrated male pigs selected after slaughter either from 125 Duroc*Landrace (Experiment 1) or 102 Tia Meslan*Landrace (Experiment 2) crossbred animals, and showing large variability in LL IMF content: from <1.5 to >3.5% in Experiment 1 and from 1.25 to 3.25% in Experiment 2. Results from lipid analyses indicate that in both experiments, an increase in IMF content is almost entirely reflected by an increase in the triglycerides content of the muscle. In Experiment 2, higher IMF content was associated with higher free fatty acids. Marbling score was significantly affected by IMF level in Experiment 1 but not in Experiment 2. In Experiment 1, a trend towards a favourable effect of high IMF levels on flavour (p=0.09) and tenderness (p=0.055) was observed. In experiment 2, increased IMF level was associated with significantly higher juiciness and flavour scores. The results from the present study indicate that the variability in IMF level of LL muscle was almost entirely due to the variability in triglyceride contents. Favourable effects of increased IMF levels on the sensory attributes of pork were demonstrated in both experiments using different types of animals, but the nature and the magnitude of these effects depended on the experiment considered. PMID- 22062934 TI - Influence of intramuscular fat content on the quality of pig meat - 2. Consumer acceptability of m. longissimus lumborum. AB - The present study is part of a project which aimed to examine the influence of intramuscular fat (IMF) content on sensory attributes and consumer acceptability of pork. Two experiments were conducted to evaluate consumer acceptability of pork chops with varying IMF level in muscle Longissimus lumborum (LL). Each experiment used 32 castrated male pigs selected after slaughter either from 125 Duroc * Landrace (Experiment 1) or 102 Tia Meslan * Landrace (Experiment 2) crossbred animals, and showing large variability in LL IMF content: from <1.5 to >3.5% in Experiment 1 and from 1.25 to 3.25% in Experiment 2. A group of 56 consumers evaluated various items on rib-eye (LL muscle trimmed of backfat) (Experiment 1) and on entire chops trimmed of backfat (Experiment 2). Data from Experiment 1 indicate that an increase in IMF level is associated with an increase in visual perception of fat and a corresponding decrease in the willingness to eat and purchase the meat, when expressed before tasting. The latter effect disappeared after the consumers had tasted the meat, probably due to a positive effect of increase IMF, up to 3.5%, on the perception of texture and taste. In Experiment 2, where entire chops were evaluated, the perception of visible fat was not affected by IMF level, probably due to the lack of variation in the level of intermuscular fat between the four IMF groups. The willingness to eat and purchase the meat were unaffected by IMF level, whereas the perception of texture and taste was enhanced with increased IMF levels up to 3.25%. The present data suggest that the acceptability of pork may be improved by increasing IMF level but: (1) this effect disappeared for IMF levels higher than 3.5%, which are associated with a high risk of meat rejection due to visible fat and (2) the positive effect of increased IMF probably holds true as long as it is not associated with an increase in the level of intermuscular fat. PMID- 22062935 TI - A case of turtleback liver. PMID- 22062936 TI - Fatigue in cirrhosis: is transplant the answer? PMID- 22062937 TI - Endoscopic ultrasonography-guided core biopsy diagnosis of giant adrenal myelolipoma. PMID- 22062938 TI - Accountable care organizations. PMID- 22062939 TI - Intractable childhood epilepsy: choosing between the treatments. AB - Intractable epilepsy is a significant problem affecting approximately 1 in 10 children with seizures. This is traditionally defined as a failure to respond to at least 2 anticonvulsant drugs tried at reasonable doses for several weeks. Although involving a minority of those with epilepsy, these children typically have significant morbidity, detrimental effects on quality of life, and often require hours of time from a child neurologist in their care. In this review and special issue, a practical approach to management options for children who have refractory epilepsy will be presented from experts in the field. PMID- 22062940 TI - The evaluation of treatment-resistant epilepsy. AB - An estimated 10% to 40% of children with epilepsy have treatment-resistant epilepsy. Persistent seizures have negative psychosocial, behavioral, cognitive, and financial consequences and are associated with an increased mortality rate. Accurate syndromic and etiologic diagnoses are of vital importance because they may guide medical and/or surgical decision making. Revisitation of the history to confirm the diagnosis of epilepsy and the appropriateness of medication trials to date is vital. Routine imaging should include structural magnetic resonance imaging (MRI) with an established epilepsy protocol. In the setting of a normal previous MRI, repeat imaging may be indicated and may be supplemented with other imaging modalities. The admission for prolonged inpatient video-encephalographic monitoring may lead to a revision of a pre-existing diagnosis. Laboratory evaluations should include genetic, metabolic, and infectious/inflammatory studies when indicated. In this review, we discuss the implication of seizure semiology and syndrome classification when searching for an underlying diagnosis in treatment-resistant epilepsy, and will review both basic and more advanced procedures/studies that may aid diagnosis. PMID- 22062941 TI - Pharmacologic treatment of intractable epilepsy in children: a syndrome-based approach. AB - The successful pharmacologic treatment of intractable childhood epilepsy is predicated upon an accurate classification of the epilepsy syndrome. The selection of an antiepileptic drug is facilitated by the knowledge of syndrome specific efficacy, the anticipation of potential side effects, and a careful risk benefit assessment tailored to each patient. As such, the identification of comorbidities and careful monitoring for treatment-emergent adverse events, especially cognitive and behavioral effects, is of utmost importance. Especially in refractory cases, polypharmacy may increase the likelihood of side effects, but carefully chosen combinations can result in synergistic benefit. For most epilepsy syndromes, newer antiepileptic drugs typically yield equivalent efficacy and superior tolerability. Nevertheless, continued research is needed to further contrast the syndrome-specific efficacy and tolerability of available drugs and to foster the development of new agents with superior efficacy and side effect profiles. PMID- 22062942 TI - Metabolic treatments for intractable epilepsy. AB - When a child on anticonvulsant medications continues to have seizures, what other options should be considered? Over the past 100 years, dietary therapies for the treatment of intractable epilepsy have become more widely recognized, and their use has continued to expand throughout the world. An increasing number of studies has shown efficacy of these metabolic treatments in improving seizure control. Currently, 4 types of dietary therapy are available in the clinic: the classic long chain fatty acid "ketogenic" diet, the medium chain triglyceride diet, the modified Atkins diet, and the low glycemic index treatment. These therapies should be considered earlier in the treatment of intractable epilepsy because they offer a different approach to treatment that has proven efficacious, tolerable, and cost-effective. PMID- 22062943 TI - Neurostimulation: vagus nerve stimulation and beyond. AB - Patients with medically intractable epilepsy who are not candidates for epilepsy surgery could benefit from neurostimulation. At this time, vagus nerve stimulation (VNS) therapy is the only Food and Drug Administation-approved neurostimulation modality; it has been shown to be efficacious and just as well tolerated in children and adolescents as in adults. Notwithstanding the initial cost of the device and implantation, VNS therapy has been shown to be a cost effective treatment, reducing direct medical costs and improving health-related quality of life measures. Deep brain stimulation of various brain regions, especially the anterior nucleus of the thalamus and responsive neurostimulation, also appear effective but are not yet approved for clinical use. Repetitive transcranial magnetic stimulation, which is also in early clinical development, is promising and could become available in the not too distant future. PMID- 22062944 TI - Surgical management of intractable childhood epilepsy: curative and palliative procedures. AB - Epilepsy surgery is increasingly used to treat intractable childhood-onset epilepsy although it remains an underused treatment option. Advances in technology allowing more accurate identification of the epileptogenic zone along with a better understanding of the benefits of both curative and palliative epilepsy surgery have resulted in an increase of potential candidates. This review covers factors contributing to medical intractability and then details the evaluation of potential surgical candidates. We discuss pre-, peri-, and postoperative variables that lead to curative procedures and highlight the role of palliative epilepsy surgery in cases in which seizure freedom is unlikely. PMID- 22062945 TI - Herbs in epilepsy: evidence for efficacy, toxicity, and interactions. AB - Herbs and dietary supplements enjoy widespread use in the treatment of epilepsy although supportive data yielding efficacy and safety are lacking. Ten specific products, American hellebore, betony, blue cohosh, kava, mistletoe, mugwort, pipsissiwa, skullcap, valerian, and melatonin, have either multiple-cited recommendations for use in epilepsy or a rationale for antiepileptic action and are discussed in detail. These items paradoxically often have a proconvulsant effect in addition to potentially serious adverse effects. Herb-drug interactions also occur at the level of the P450 hepatic enzyme system of drug catabolism and the P-glycoprotein transport system regulating the entry of exogenous compounds into the vasculature or blood-brain barrier. Thus, significant pharmacokinetic interactions may occur, in addition to pharmacodynamic interactions and proconvulsant effects of alternative medications themselves. Patients should be inquired as to the nature of any alternative medicine products they are using, with the view that these products may be reasonable if traditional antiepileptic drug therapy is continued, potential adverse effects of the alternative agents are monitored, and the alternative and traditional agents do not conflict. PMID- 22062946 TI - Counseling of parents of a child with uncontrollable seizures. AB - This review deals with the problem of counseling parents of children with intractable epilepsy. The previous topics address the complexity of the pathophysiology and the treatment options available both mainstream and alternative. However, knowing the reasons for intractability or the reasons for treatment failure may be insufficient to guide the health care professional in trying to help families deal with this problem on a day-to-day basis. There is no greater challenge for the epilepsy professional than caring for this group of patients. How do we help the parents of children we cannot help? Although we may not be able to eliminate seizures, we can be accessible and listen openly. We can try and help families develop strategies, skills, and resources that empower them to manage their situation more effectively. PMID- 22062947 TI - Activation of VEGFR-2 signaling in response to moderate dose of ultraviolet B promotes survival of normal human keratinocytes. AB - Mounting evidence indicates that signaling via VEGF receptors (VEGFRs) extends beyond blood vessel formation. Recently, VEGFRs are also found to be constitutively expressed in keratinocytes and epidermal appendages. Here, we show that the expression of VEGFRs (including VEGFR-1, VEGFR-2, and NRP-1) was significantly enhanced by moderate dose of ultraviolet B (UVB) in normal human keratinocytes and epidermis. The elevated expression of VEGFRs by UVB was independent of autocrine stimulation by their natural ligand, VEGF, but mainly mediated through hypoxia and oxidative stress. Moderate dose UVB also promoted tyrosine phosphorylation of VEGFR-1 and VEGFR-2, this effect was again VEGF independent. Both alpha and delta isoforms of protein kinase C (PKC) were required for UVB-induced phosphorylation of VEGFR-1, but only the delta isoform was required for VEGFR-2 phosphorylation. The phosphorylation of VEGFRs or isoforms of PKC was completely inhibited by PP2, a specific inhibitor for Src family kinases (SFKs), indicating that SFKs are upstream of PKC and VEGFRs. Moderate dose UVB-induced VEGF exerted an anti-apoptotic effect for keratinocytes, whereas high dose UVB-induced VEGF played as an inflammatory factor. Of note, neutralization of VEGFR-2 but not VEGFR-1 exacerbated UVB induced cell death and reduced survival of keratinocytes. Furthermore, VEGFR-2 neutralization inhibited the activation of ERK1/2 and Akt by UVB, suggesting that VEGFR-2 signaling was involved in the pro-survival mechanism via ERK1/2 and PI3 K/Akt pathway. Taken together, we demonstrate for the first time that VEGFR-2 signaling is activated and promotes survival of keratinocytes under moderate dose of UVB irradiation. PMID- 22062948 TI - RhoA and Rho kinase mediate cyclosporine A and sirolimus-induced barrier tightening in renal proximal tubular cells. AB - The regulation and maintenance of the paracellular transport in renal tubular epithelia is vital for kidney functions. Combination of the immunosuppressant drugs cyclosporine A (CsA) and sirolimus (SRL) exerts powerful immunosuppression, but also causes nephrotoxicity. We have previously shown that CsA and SRL elevate transepithelial resistance (TER) in kidney tubular cells partly through MEK/ERK1/2. In this work we examined the hypothesis that the RhoA pathway may also be mediating effects of CsA and SRL. We show that CsA and the CsA/SRL combination activated RhoA, induced cofilin phosphorylation and promoted stress fiber generation. The Rho kinase (ROK) inhibitor, Y27632, prevented CsA and CsA/SRL-induced cofilin phosphorylation and actin remodelling, reduced the TER increase and prevented the rise in claudin-7 levels caused by the drugs. Expression of the exchange factor GEF-H1/lfc was elevated in cells treated with CsA and CsA/SRL. GEF-H1 silencing inhibited RhoA activation by ~50%, and potently reduced cofilin phosphorylation and stress fiber formation induced by CsA and CsA/SRL. However, GEF-H1 downregulation did not prevent the TER change. Thus the Rho/Rho kinase pathway was involved in mediating CsA and CsA/SRL-induced cytoskeleton rearrangement and TER changes via claudin-7 expression. Our data however point to differential regulation of Rho activation involved in central cytoskeleton remodelling, that is GEF-H1-dependent and junctional permeability that does not require GEF-H1. PMID- 22062949 TI - Omega-3 fatty acids enhance mitochondrial superoxide dismutase activity in rat organs during post-natal development. AB - The protection of the developing organism from oxidative damage is ensured by antioxidant defense systems to cope with reactive oxygen species (ROS), which in turn can be influenced by dietary polyunsaturated fatty acids (PUFAs). PUFAs in membrane phospholipids are substrates for ROS-induced peroxidation reactions. We investigated the effects of dietary supplementation with omega-3 PUFAs on lipid peroxidation and antioxidant enzyme activities in rat cerebrum, liver and uterus. Pups born from dams fed a diet low in omega-3 PUFAs were fed at weaning a diet supplying low alpha-linolenic acid (ALA), adequate ALA or enriched with eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA). Malondialdehyde (MDA), a biomarker of lipid peroxidation, and the activities of superoxide dismutase 1 (SOD1), SOD2, catalase (CAT) and glutathione peroxidase (GPX) were determined in the three target organs. Compared to low ALA feeding, supplementation with adequate ALA or with EPA+DHA did not affect the cerebrum MDA content but increased MDA content in liver. Uterine MDA was increased by the EPA+DHA diet. Supplementation with adequate ALA or EPA+DHA increased SOD2 activity in the liver and uterus, while only the DHA diet increased SOD2 activity in the cerebrum. SOD1, CAT and GPX activities were not altered by ALA or EPA+DHA supplementation. Our data suggest that increased SOD2 activity in organs of the growing female rats is a critical determinant in the tolerance to oxidative stress induced by feeding a diet supplemented with omega-3 PUFAs. This is may be a specific cellular antioxidant response to ROS production within the mitochondria. PMID- 22062950 TI - MicroRNA212/132 family: molecular transducer of neuronal function and plasticity. AB - MicroRNAs (miRNAs) are small non-coding RNAs that mediate post-transcriptional gene silencing. It is increasingly clear that miRNAs are key regulatory factors for a tight gene expression control. MiRNAs are involved in many aspects of organism development and function, in physiological and pathological conditions. MiRNA expression varies with cell type, tissue and developmental stages. The microRNA212/132 family is one of the most studied miRNA family due to the involvement of miR132 and miR212 in important cellular processes, especially in the brain. MiR132 and miR212 have been implicated in tissue development and in the formation and plasticity of neuronal connections. The main aim of this review is to highlight recent discoveries about miR212/132 family functions and its possible involvement in pathological processes. PMID- 22062951 TI - Characterization of glyceraldehyde-3-phosphate dehydrogenase as a novel transferrin receptor. AB - A majority of cells obtain of transferrin (Tf) bound iron via transferrin receptor 1 (TfR1) or by transferrin receptor 2 (TfR2) in hepatocytes. Our study establishes that cells are capable of acquiring transferrin iron by an alternate pathway via GAPDH. These findings demonstrate that upon iron depletion, GAPDH functions as a preferred receptor for transferrin rather than TfR1 in some but not all cell types. We utilized CHO-TRVb cells that do not express TfR1 or TfR2 as a model system. A knockdown of GAPDH in these cells resulted in a decrease of not only transferrin binding but also associated iron uptake. The current study also demonstrates that, unlike TfR1 and TfR2 which are localized to a specific membrane fraction, GAPDH is located in both the detergent soluble and lipid raft fractions of the cell membrane. Further, transferrin uptake by GAPDH occurs by more than one mechanism namely clathrin mediated endocytosis, lipid raft endocytosis and macropinocytosis. By determining the kinetics of this pathway it appears that GAPDH-Tf uptake is a low affinity, high capacity, recycling pathway wherein transferrin is catabolised. Our findings provide an explanation for the detailed role of GAPDH mediated transferrin uptake as an alternate route by which cells acquire iron. PMID- 22062952 TI - A new c.1845A->T of oncostatin M receptor-beta mutation and slightly enhanced oncostatin M receptor-beta expression in a Chinese family with primary localized cutaneous amyloidosis. AB - Primary localized cutaneous amyloidosis (PLCA) is a chronic itching skin disease with amyloid material deposited in the upper dermis. PLCA is more common in Southeast Asia and South America, where up to 10% of cases may be familial. Mutations of OSMR or IL31RA have been identified in PLCA. Here we detected a new OSMR mutation in a lichenoid PLCA family from north China. This is the first report of PLCA with gene mutation on the Chinese mainland. A heterozygous 1845A >T was found in exon 13 of the proband, causing p.Lys615Asn substitution, which was not found in screening 100 ethnically matched healthy controls. The particular mutated amino acid is well conserved throughout various evolutionary lineages, located within the second fibronectin III-like domain of oncostatin M receptor beta subunit (OSMRbeta), and in close vicinity to a previously reported mutation, p.Gly618Ala. Immunohistochemistry showed slightly enhanced OSMRbeta expression in the lesion of the proband. This study extends the knowledge of PLCA gene mutation and further supports the pathogenic role of OSMRbeta in PLCA. PMID- 22062953 TI - Quaero muneris: exploring microRNA function in cardiovascular disease. PMID- 22062954 TI - MicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine hearts. AB - Cardiac progenitor cells (CPCs) are multipotent cells that may offer tremendous potentials for the regeneration of injured myocardium. To expand the limited number of CPCs for effective clinical regeneration of myocardium, it is important to understand their proliferative potentials. Single-cell based assays were utilized to purify c-kit(pos) CPCs from human and mouse hearts. MicroRNA profiling identified eight differentially expressed microRNAs in CPCs from neonatal and adult hearts. Notably, the predicted protein targets were predominantly involved in cellular proliferation-related pathways. To directly test this phenotypic prediction, the developmental variance in the proliferation of CPCs was tested. Ki67 protein expression and DNA kinetics were tested in human and mouse in vivo CPCs, and doubling times were tested in primary culture of mouse CPCs. The human embryonic and mouse neonatal CPCs showed a six-fold increase in Ki67 expressing cells, a two-fold increase in the number of cells in S/G2-M phases of cell cycle, and a seven-fold increase in the doubling time in culture when compared to the corresponding adult CPCs. The over-expression of miR 17-92 increased the proliferation in adult CPCs in vivo by two-fold. In addition, the level of retinoblastoma-like 2 (Rbl2/p130) protein was two-fold higher in adult compared to neonatal-mouse CPCs. In conclusion, we demonstrate a differentially regulated cohort of microRNAs that predicts differences in cellular proliferation in CPCs during postnatal development and target microRNAs that are involved in this transition. Our study provides new insights that may enhance the utilization of adult CPCs for regenerative therapy of the injured myocardium. PMID- 22062955 TI - Erythropoietin induces positive inotropic and lusitropic effects in murine and human myocardium. AB - Initial clinical studies indicate a potential beneficial effect of erythropoietin (EPO) in patients with anemia and heart failure. Here, we investigate the direct contractile effects of erythropoietin on myocardial tissue. Treatment with EPO (50U/mL) using excitable murine and human left ventricular muscle preparations resulted in a 37% and 62% increase in twitch tension, respectively (P<0.05). Isolated murine cardiomyocytes exposed to EPO demonstrated a 41% increase in peak sarcomere shortening (P=0.012). Using compounds that specifically stimulate a non erythropoietic EPO receptor yielded similar increases in contractile dynamics. Cardiomyocyte Ca(2+)dynamics showed an 18% increase in peak calcium in EPO treated cardiomyocytes over controls (P=0.03). Studies in muscle strips skinned after EPO treatment demonstrated a phosphorylation dependant increase in the viscous modulus as well as an increase in oscillatory work. The EPO mediated increase in peak sarcomere shortening was abrogated by PI3-K blockade via wortmannin and by non-isozyme specific PKC blockade by chelerythrine. Finally, EPO treatment resulted in an increase in PKCepsilon in the particulate cellular fraction, indicating activation of this isoform. EPO exhibits direct positive inotropic and lusitropic effects in cardiomyocytes and ventricular muscle preparation. These effects are mediated through PI3-K and PKCepsilon isoform signaling to directly affect both calcium release dynamics and myofilament function. PMID- 22062956 TI - Mapping protein receptor-ligand interactions via in vivo chemical crosslinking, affinity purification, and differential mass spectrometry. AB - Protein receptor-ligand interactions play important roles in mediating enzyme catalysis, signal transduction, and other protein functions. Immunoaffinity purification followed by mass spectrometry analysis is a common method for identifying protein receptor-ligand complexes. However, it is difficult to distinguish between specific protein binding partners and non-specifically bound proteins that co-purify with the complex. In addition, weakly interacting binding partners may dissociate from the protein receptor-ligand complexes during immunoaffinity purification. The combination of chemical crosslinking, affinity purification, and differential mass spectrometry analysis provides a direct method for capturing stable, weak, and transient protein interactions that occur in vivo and in vitro. This approach enables the identification of functional receptor-ligand binding partners with high confidence. Herein, we describe a differential mass spectrometry approach coupled with in situ chemical crosslinking and immunoaffinity purification for identifying receptor-ligand binding partners. In particular, we identified a functional, counter-ligand structure of the natural killer cell p30-related protein. PMID- 22062957 TI - Development of an immunopredictor for the evaluation of the risk of cardiovascular diseases based on the level of soluble P-selectin. AB - Due to its physiologic role in modulating adhesive interactions between blood cells and the endothelium during inflammatory processes or at injury sites, the adhesion molecule P-selectin is of great interest. The level of soluble P selectin in plasma or serum can be detected and used as a clinical predictor for adverse cardiovascular events, leading to the presumption that it is secreted, shed or cleaved from the cell membrane during the process of diseases. Increased levels of soluble P-selectin in the plasma have been shown to be associated with a range of cardiovascular disorders, including coronary artery disease, hypertension and atrial fibrillation. Therefore, it is of huge significance to develop simple, rapid and sensitive methods for the detection of such pathological predictors, not only for facilitating the surveillance of cardiovascular mortality/sudden cardiac death, but also for effectively monitoring the drug potency on platelets based on measurement of P-selectin performed on fixed blood samples following platelet stimulation in whole blood in a remote setting. We herein developed a simple, yet novel and sensitive electrochemical sandwich immunosensor for the detection of P-selectin; it operates through covalent linkage of anti-P-selectin antibody on CNT@GNB nanocomposites-modified disposable screen-printed electrode as the detection platform, with the potassium ferrocyanide-encapsulated, anti-P-selectin-tagged liposomal biolabels as the electrochemical signal probes. The immunorecognition of the sample P-selectin by the liposomal biolabels occurred on the surface of the electrodes; the release of potassium ferrocyanide from the bound liposomal biolabels extensively contributed to the increase in electrochemical signal, which was acquired in HCl solution at +0.32V in square wave voltammetry mode. The resulting sigmoidally shaped dose-response curves possessed a linear dynamic working range from 1*10(-13) to 1*10(-5)g/mL. This liposome-based electrochemical immunoassay provides an amplification approach for detecting P-selectin at trace levels, leading to a detection limit as low as 4.3fg (equivalent to 5MUL of 0.85pg/mL solution). A commercially available ELISA kit was used as a reference method to validate the newly-developed assay through the analysis of mouse serum samples. A strong correlation was observed between the two data sets as the R squared value of 0.997 from the linear regression line. This electrochemical immunosensor will be useful for the detection of P-selectin in biological fluids and tissue extracts. PMID- 22062958 TI - Quality characteristics of reduced-fat Chinese-style sausage as related to chitosan's molecular weight. AB - Microbiological and physicochemical characteristics of reduced-fat (approximately 22%) Chinese-style sausages containing 0.1% chitosan (in 1% lactic acid solution) with three different molecular weights [low molecular weight chitosan (CHL), MW= 150 kDa; medium molecular weight chitosan (CHM), MW=600 kDa; high molecular weight chitosan (CHH), MW=1250 kDa] were demonstrated. Sausages were also subject to oven heating or deep-fat frying for sensory evaluation. Treatments containing chitosan were lower in pH at any storage periods than the control (CONT). Generally speaking, total plate counts and lactic acid bacteria counts of all treatments slightly increased, with CHL being the lowest. However, all bacterial counts were lower than 7 [log colony forming unit (CFU)/g] at the end of storage. Results from sensory evaluation showed that deep-fat fried sausages from treatments CHL and CHM were higher in overall acceptability. This study demonstrated that the addition of chitosan to reduced-fat Chinese-style sausage resulted in no detrimental effect on textural properties. PMID- 22062959 TI - Reaction to boar odour by different South African consumer groups. AB - A consumer sensory study of South African pork consumers (n=300) including equal numbers of males and females and consumers from three ethnic groupings (black, white and coloured consumers) was conducted to determine the effects of gender and ethnicity on consumer reactions towards boar odour compounds. Samples consisted of boar fat with varying concentrations of skatole and androstenone. Each consumer evaluated the odour of seven fat samples. Consumers' liking of pork meat in general had a significant effect on the hedonic rating of the boar odour. The majority of consumers represented in this study would be dissatisfied with pork meat exhibiting detectable levels of skatole. In general, more females compared with males, will also respond more negatively towards samples with detectable levels of androstenone. An apparent liking for samples with medium levels of androstenone (0.5-1 MUg/g) was found for some consumers, especially males, and can be partly attributed to the inability of some consumers to smell this compound at these levels or a genuine liking for the odour of androstenone. Significant differences in the sensitivity of consumers from different ethnic groups were found with white females responding more negatively than white males and blacks. Although it was not possible to compare responses directly with the white and black groups, it was found that a higher percentage of coloureds responded negatively to boar odour compounds. Coloured males responded particularly negatively towards samples with detectable skatole, while black males, in general, were found to be more critical than black females. Based on these results it is predicted that the majority of consumers would be less willing to consume pork meat exhibiting detectable levels of boar odour. PMID- 22062960 TI - Free amino acids and other non-volatile compounds formed during processing of Iberian ham. AB - Fifty-five legs from Iberian pigs were traditionally processed into dry cured hams. Free amino acids and other non-volatile compounds in the water-soluble fraction from the biceps femoris muscle were analyzed by HPLC. At the drying stage and in the last months in the cellar the largest increases in these water soluble compounds took place. There was a clear influence on free amino acid formation of salt content and on the formation of peptides of the temperature at each processing stage. As the amount of non-volatile compounds in the water soluble fraction increases with processing time, their determination could provide a maturation index for Iberian ham. PMID- 22062961 TI - Quality properties of pork sausage prepared with water-soluble chitosan oligomer. AB - Emulsion type sausage was prepared with the addition of a chitosan oligomer (molecular weight 5000, 0.2%) and compared to a control. Sausages were aerobic- or vacuum-packaged and stored in a 4 degrees C refrigerator for 3 weeks. Difference of microbial growth between the sample with added chitosan oligomer or control was not observed (P>0.05). Lipid oxidation was lower in the sausage with chitosan oligomer at 3 weeks in aerobic packaging (P<0.05) than in the control sausage. The surface color of the sausage with chitosan oligomer had higher Hunter color L*- and b*-value. Hunter color a*-values were lower in the chitosan oligomer-added sausage and the a*-value increased during storage regardless of packaging (P<0.05). Sensory panels did not detect any difference in color, flavor, texture, and overall acceptance, and mechanical texture analysis also showed no difference. Therefore, the quality of the sausage with added chitosan oligomer (0.2%) was acceptable. PMID- 22062962 TI - Characterization of traditional processing of pork meat into boucane. AB - Boucane is a traditional meat product from Reunion that is obtained by salting, drying and hot smoking pork belly. One-step unit operations give rise to a stable product with remarkable colour and flavour qualities. Smoking the product directly over embers, however, leads to benzo(a)pyrene contamination. Mass transfers (salt gain, water loss) stabilize the end product, which has a 28.5% water content and 5.6% salt content. Lipid oxidation and Maillard reactions are the main mechanisms involved in the boucane production process. The molecules derived from these two reactions are - along with smoke compounds - responsible for the flavour and colour of the end product. PMID- 22062963 TI - Biogenic amine accumulation in ripened sausages affected by the addition of sodium sulphite. AB - The effect of two concentrations of sodium sulphite on biogenic amine accumulation during the ripening of slightly fermented sausages was examined. Three batches of sausages were manufactured: one without sulphite (control), one with 500 mg/kg and one with 1000 mg/kg of sodium sulphite. Considerable tyramine production (75-140 mg/kg dry matter [dm]) was observed in all batches. Sausages with sulphite, especially those with 500 mg/kg, accumulated higher amounts of tyramine than those without sulphite. Cadaverine was observed in the batch without sulphite (38 mg/kg dm), but its production was markedly inhibited by the presence of sulphite. A small amount of putrescine (4-12 mg/kg dm) was found during ripening and its final content was slightly higher in sausages with 1000 mg/kg of sulphite. No production of histamine, phenylethylamine or tryptamine was observed. Agmatine and spermine levels decreased during ripening, whereas spermidine levels remained constant. Although sausages with sulphite showed lower microbial counts, only cadaverine production was lower than in sausages without sulphite. In contrast, tyramine and putrescine production seemed to be stimulated by the presence of sodium sulphite. PMID- 22062964 TI - Strategic finishing feeding as a tool in the control of pork quality. AB - A standard diet and two finishing feeding strategies known to reduce muscle glycogen stores were investigated in combination with exercise immediately prior to slaughter in pigs. The objective was to determine the influence of muscle glycogen at slaughter on temperature and pH in post-mortem muscle, the colour, drip loss and Warner-Bratzler shear force of the meat. The muscle glycogen stores were reduced by strategic finishing feeding. In general, pH(45 min) was higher in muscles from strategically fed pigs compared with control pigs. Exercise also resulted in higher pH(45 min) in control pigs compared to non-exercised control pigs, while the opposite was seen in muscles from strategically fed pigs. Exercise resulted in higher muscle temperatures in the carcasses irrespective of feeding strategy. pH(24 h) were higher in M. biceps femoris and M. semimembranosus from exercised, strategically fed pigs compared with the corresponding controls. In contrast, irrespective of feeding strategy no difference in pH(24 h) was registered in the meat of non-exercised pigs. Drip loss was lower in meat of strategically fed pigs compared with meat of control pigs. Moreover the drip loss was lowest in the meat of non-exercised pigs. The present study shows that strategic finishing feeding has high potential for the control of pork quality. PMID- 22062965 TI - Relationship between lipid peroxidation and fat content in Japanese Black beef Longissimus muscle during storage. AB - We examined the relationship of crude fat content to lipid peroxidation of beef during storage. Longissimus muscle samples (fat content; 6.5-39.4%) from 27 Japanese Black beef steers were stored for 1, 4, 7 and 10 days, and thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH) were determined. TBARS values increased significantly (P<0.05), but LOOH did not change during the 10- day storage period. TBARS values were negatively correlated (P<0.05) with fat content in samples stored for 1, 4, 7 and 10 days. LOOH values, however, were not significantly correlated with fat content except on day 1. Phospholipid contents were correlated (P< 0.01) with LOOH values on each measurement day, but not significantly correlated with TBARS values except on day 1. These findings indicated that: (1) high-fat beef had high preservative properties, and that; (2) TBARS formation was correlated with LOOH derived from phospholipid oxidation in the initial period of storage, and was correlated directly with fat content in a later period. PMID- 22062966 TI - Chromatographic analysis of cadaverine to detect incipient spoilage in mutton. AB - Suitability of measuring cadaverine for rapid assessment of bacterial quality of fresh and stale mutton (showing signs of incipient spoilage) was examined. HPTLC for rapid screening and detection and HPLC for accurate quantification was employed. Analysis of over 150 samples of varying degrees of freshness and postmortem age showed that in more than 90% of the samples, no cadaverine was detectable when meat was deemed acceptable with <10(6) orgs/g. However, when meat showed incipient spoilage, as judged by off odour and dull colour, cadaverine was detected in the range of 1-5 ppm. Such meat samples had a bacterial load of 10(7) orgs / g or more. HPTLC analysis allowed the simultaneous analysis of 5-6 samples and the total time including extraction was 1.5-2 h. As only easily available chemicals and equipment were required, it was a simple, rapid and inexpensive technique. HPTLC detection of cadaverine can therefore be recommended for the rapid assessment of bacterial quality of mutton and HPLC can be used for accurate quantification. PMID- 22062967 TI - Evidence against the non-enzymatic calcium theory of tenderization. AB - The objective of the present study was to determine whether variation in the tenderization of lamb longissimus could be attributed to variations in the rise in free calcium postmortem and sarcomere lengthening post rigor. The longissimus muscle of 10 crossbred lambs (Romney*Coopworth) was sampled at 1 and 7 days postmortem for determination of MIRINZ shear force, myofibrillar fragmentation index (MFI), sarcomere length, free calcium, and proteolysis of troponin-T. Despite considerable variation in tenderness and tenderization of the muscles, sarcomere lengthening was not observed. The concentration of free calcium at 7 days postmortem correlated significantly with the MFI (r=0.640; P<0.05) and tended to correlate with the shear force (r=-0.596; P<0.1) and degradation of troponin-T (r=0.625; P<0.1). Degradation of troponin-T was significantly correlated with tenderization (r=0.664; P<0.05). Troponin-T is a calpain substrate, but reportedly is not degraded through a direct effect from calcium. The present results, therefore, suggest that the variation in free calcium in postmortem muscle affects tenderization through an effect on the calpain system and not through a direct effect of calcium on myofibrillar proteins. Consequently, the results of this study do not support the (calcium) theory that calcium directly affects tenderization. PMID- 22062968 TI - Factors affecting the composition and amount of 'white exudate' from cooked bacon. AB - Bacon sometimes produces a white, unsightly fluid that exudes from the surfaces during cooking -a phenomenon that has resulted in frequent consumer complaints. The quantity of exudate from bacon of known history was assessed subjectively, by ranking photographs following 'dry-frying', and objectively, by collecting exudate in an ice cooled tray after grilling. Trained assessors ranked samples in order of visible exudate as follows: dry cured4.5%)) in drip loss were not discriminated. Predicting drip loss with NIRS early post mortem is not successful, although NIRS in the slaughter line has potential as a fast predictor of intra-muscular fat. Possibilities for using the NIRS technique to get to know more about muscle metabolism and post mortem changes are promising. PMID- 22062980 TI - Effect of pelvic suspension and cooking method on the processing and sensory properties of hams prepared from two pork muscles. AB - The effect of two hanging methods (Achilles and aitch-bone) and two cooking methods (normal and Delta-T (DeltaT)) on the quality of cooked hams produced from two muscles, M. semimembranosus (topside) and M. biceps femoris (silverside) was examined. Pork sides were hung by the Achilles tendon (conventional) or the aitch bone (pelvic suspension) 1 h post-slaughter and chilled for 24 h at 1 degrees C. The hams were steam-cooked using a 'normal' cooking cycle (cooked at 85 degrees C to a core temperature of 72 degrees C) or a 'DeltaT' cycle (maintaining a constant difference, of 35 degrees C, between oven and core temperatures until the oven reaches 85 degrees C, whereupon the core is allowed to come up to 72 degrees C). Pelvic suspension increased (P?0.01) the brine uptake of silverside hams, by 2.6%, but not of topside. The DeltaT cooking method had a significant effect (P?0.05) for both muscles, reducing cook losses by 2.3% units in the topside hams and 3.3% in the silverside hams, compared to the normal continuous cook. Pelvic suspension resulted in slightly (P?0.05) more tender and juicy hams from silverside but not from topside. Both hanging method (Achilles and Aitch bone) and cooking method (normal and DeltaT) affected silverside ham more than topside ham. The overall result was that a combination of pelvic suspension and DeltaT cooking had a positive effect on the quality of cooked hams, particularly hams produced from the silverside. PMID- 22062981 TI - Determination of C22:5 and C22:6 marine fatty acids in pork fat with Fourier transform mid-infrared spectroscopy. AB - Fatty acids in samples (n=74) of pork adipose tissue were measured with a Fourier transform mid-infrared (FT-MIR) spectrometer and by gas chromatography. The measured absorption spectra provided information to estimate partial least squares regression models for fatty acid groups, the iodine value and several fatty acids. The iodine values were predicted with correlation coefficient R=0.996 and root mean square error of cross-validation RMSECV=0.658. The sum of the two marine fatty acids of main interest, C22:5n3+C22:6n3, were predicted with R=0.982 and RMSECV=0.062. The K nearest neighbours procedure successfully classified the samples in three classes, depending on their proportions of marine fatty acids. Application of fat and absorption measurements were rapid, requiring less than 5 min of labour per sample. The results reported in this paper demonstrate that FT-MIR measurements can serve as a rapid method to determine marine fatty acids in pork fat. PMID- 22062982 TI - Color and thiobarbituric acid values of cooked top sirloin steaks packaged in modified atmospheres of 80% oxygen, or 0.4% carbon monoxide, or vacuum. AB - Case-ready fresh beef is typically packaged in a modified-atmosphere with approximately 80% oxygen and 20% carbon dioxide. Recently, USDA approved distribution of fresh meats in a master bag system using 0.4% carbon monoxide (CO). This study compared effects of packaging system (vacuum, 80% oxygen, 0.4% carbon monoxide), fresh meat storage time (7-21 days) and cooking temperature (49 79 degrees C) on extent of myoglobin denaturation, color and rancidity in cooked top sirloin steaks. Steaks packaged in 80% oxygen or CO retained desirable red color for 14 and 21 days storage, respectively. Steaks stored in 80% oxygen exhibited the greatest TBA values and myoglobin denaturation at all storage times and cooking temperatures. Steaks stored in high oxygen developed brown interior color at internal temperatures as low as 57 degrees C, the premature browning effect. Premature browning and rancidity associated with steaks packaged in 80% oxygen was prevented by packaging in 0.4% CO or vacuum. PMID- 22062983 TI - Associations between two gene markers and indicator traits affecting fresh and dry-cured ham processing quality. AB - The study objective was to evaluate the effects of mutations in two genes, PRKAG3 and CAST, on fresh and dry-cured processing characteristics. Processing and curing followed normal commercial procedures. A 100 g sample of the semimembranosus was excised and frozen for later DNA harvest. Genotypes for CAST, and PRKAG3 were determined after DNA extraction from the frozen samples. The PRKAG3 marker had no affect on dry-cured ham processing characteristics. The CAST gene marker was a significant source (P<0.05) of variation for cured ham moisture content and tended to be a significant source (P<0.10) for yield, ham weight loss, salt content and Minolta color change. The data demonstrate that the CAST 11 genotype is associated with greater processing yields. Alternatively, selection or sorting for the CAST 22 genotype should produce cured hams that exhibit more efficient moisture loss and, as a result, require less processing time and contain greater salt content. PMID- 22062984 TI - Performance of Cinta Senese pigs reared outdoors and indoors. 1. Meat and subcutaneous fat characteristics. AB - The effects of rearing system on tissue composition of a sample joint and on chemical-physical traits of meat and subcutaneous fat were studied in an Italian local pig breed. Forty-six Cinta Senese pigs were used; 17 pigs were reared on wood pasture, 29 pigs were reared in pens and fed commercial mixtures. Weight at slaughter was 136.2 and 127.7 kg for indoor and outdoor-pigs respectively. For sample joint composition outdoor-pigs showed a lower percentage of Longissimus lumborum (Ll) (46% vs. 48%) and higher percentages of intermuscular fat (7.2% vs. 4.7%) and bone (20.9% vs. 19.2%). In Ll outdoor-pigs showed higher percentages of intramuscular fat (4.04% vs. 3.29%) and crude protein (23.5% vs. 22.8%), lower drip and cooking losses by oven (0.66% vs. 2.14% and 28.6% vs. 32.3% respectively) and higher cooking loss by water-bath (30.3% vs. 26.6%). Lower values of L* (45.8 vs. 50.1) and higher values of a* (14.9 vs. 11.8) and chroma (15.9 vs. 12.8) were recorded on Ll of outdoor-pigs. Subcutaneous fat of outdoor pigs showed higher percentages of MUFA (55.1% vs. 53.3%) and PUFA (13.2% vs. 10.4%). Outdoor-pigs had higher PUFA/SFA ratio (0.43 vs. 0.29). PMID- 22062985 TI - Composition and quality of Mexican and imported retail beef in Mexico. AB - Randomly selected New York steaks from domestic and imported beef were purchased in three major Mexican cities, comparing Mexican beef (from northern, central, and southern regions of the country) and American beef (USDA-Choice and ungraded No Roll). The meat was analyzed for chemical composition, Warner-Bratzler shear force (WBSF), cooking loss, color and consumer acceptability. All sources of Mexican beef and No Roll US beef had similar chemical composition. USDA-Choice beef had a higher fat content and a lower moisture and total collagen content. Mexican beef from the northern region and USDA-Choice beef had lower WBSF and redness values than the other beef sources. Overall desirability was high regarding all Mexican beef sources, and USDA-Choice beef. No Roll US beef had the lowest overall desirability score. Results indicate Mexican beef is in an advantageous position when competing with imports in the current open market. PMID- 22062986 TI - Meat quality in suckling lambs: effect of pre-slaughter handling. AB - Thirty-three suckling lambs of the Manchega breed were used to compare the effects of pre-slaughter handling (PSH) on initial meat quality and at 7 days post-mortem. Lambs were distributed into three groups: electrically stunned (ESL; n=15), stunned using CO(2) (GSL; n=10) and slaughtered without previous stunning (USL; n=8). Meat quality was evaluated by examining pH, colour (L*, a*, b* values), water holding capacity (WHC), cooking loss (CL), shear force (SF) and drip loss (DL). At 24 h post-mortem, the highest pH corresponded to the USL group (P<0.05) whereas the lowest pH decline (pH(0)-pH(24)) corresponded to the GSL group (P<0.05). Differences in pH among groups disappeared after 7 days post mortem. In general, PSH did not affect values of WHC, CL and colour parameters. After 7 days post-mortem, there were significant differences between groups in DL, this being lowest (P<0.05) in stunned animals. GSL resulted in more tender meat (lower SF value) than ESL and USL (P<0.05). Moreover, there was no blood splash in any of the carcasses of the GSL group. PMID- 22062987 TI - Proteomic analysis of water soluble and myofibrillar protein changes occurring in dry-cured hams. AB - The myofibrillar fraction of raw ham muscles and dry-cured hams with different ripening times was extracted in denaturing and reducing conditions and subjected to two-dimensional gel electrophoresis. The two-dimensional maps gave overall pictures of the already noted progressive disappearance of actin, tropomyosin and myosin light chains during ripening. In addition, two fragments from Myosin Heavy Chain proteolysis, marked as myosin chain fragments MCF1 and MCF2, were identified by immunodetection and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Furthermore, a new form of actin on two-dimensional gel was identified by MALDI-TOF peptide mapping. In 12-month old dry-cured ham, most myofibrillar proteins were completely hydrolyzed. At this stage of ripening, in fact, in some Parma and S. Daniele dry-cured ham samples, myosin heavy chain fragments and other unidentified neo-formed spots were found. Some of the sarcoplasmic proteins in water extracts from pork meat markedly decreased in amount or disappeared totally, during ripening. Surprisingly, two dimensional gel electrophoresis maps of the water soluble protein fraction from dry-cured ham showed the presence of two spots identified as tropomyosin alpha- and beta-chain. This result suggests that some of the saline soluble myofibrillar proteins can disappear from this fraction because of salt solubilization and not due to complete enzyme action. Two-dimensional gel electrophoresis (2-DGE) has proved a powerful tool to evaluate the enzymatic susceptibility of meat proteins and the evolution of protein map fragmentation throughout ripening process as well as a means of obtaining a standard fingerprinting map characterizing the final product. PMID- 22062988 TI - Exclusion of oxygen from modified atmosphere packages limits beef rib and lumbar vertebrae marrow discoloration during display and storage. AB - Visual and instrumental color (L*a*b* and reflectance from 400 to 700 nm) were used to evaluate packaging atmosphere as a way of minimizing beef marrow discoloration. In experiment 1, rib ends (n=24) packaged in 80% O(2)/20% CO(2) discolored more than ribs packaged in 100% N(2), which resulted in a relatively stable purplish marrow color through a 7-day display at 1 degrees C. In experiment 2, lumbar vertebrae (n=10) packaged in 80% O(2)/20% CO(2) had a rapid and significant discoloration within 24 h after packaging, likely because of the formation of methemoglobin. Conversely, vertebrae packaged in 80% N(2)/20% CO(2) and 0.4% CO/30% CO(2)/69.6% N(2) remained color stable during 2 and 6 weeks of storage at 4 degrees C, respectively. Exclusion of oxygen from MAP packages and the addition of low concentrations of CO minimized beef rib and lumbar vertebrae discoloration compared with high-oxygen MAP. PMID- 22062989 TI - Microbiological condition of horse meat prepared at a North American packing plant, and control of the temperatures of product air freighted to Europe. AB - To obtain information about the microbiological quality of horse meat exported from North America, the microbiological conditions of hot or cold boned primal cuts and carcass quarters from horse carcasses processed at a North American packing plant were examined. In addition, temperature histories were obtained from boxes of hot boned meat during cooling, and from horse carcass quarters air freighted to Europe. The log mean numbers of aerobes recovered from horse carcasses after dressing were >2 logcfu/cm(2). Log total numbers of coliforms and Escherichia coli recovered from 25 samples from such carcasses were >2 log and <2 logcfu/2500 cm(2), respectively. Numbers of bacteria generally similar to those were recovered from cooled carcasses or hot or cold boned cuts. The cooling process for hot boned meat met with standards for hot boned beef cooling processes based on calculated growth of E. coli at box centres. The deep tissues of carcass quarters cooled and the temperatures of their surfaces rose during air freighting, but surface temperatures mostly remained below 7 degrees C. The microbiological condition of horse carcass quarters delivered to plants in Europe would likely be comparable with the microbiological conditions of hanging beef delivered from packing plants to distant customers within North America. PMID- 22062990 TI - Conjugated linoleic acid concentration in M. Longissimus dorsi from heifers offered sunflower oil-based concentrates and conserved forages. AB - Dietary inclusion of polyunsaturated fatty acid (PUFA)-rich plant oils is one approach to improving the fatty acid profile of ruminant meat and meat products from a human health perspective. Whole crop wheat silages represent a possible alternative forage to grass silage for beef production, however, they may adversely impact the fatty acid profile of ruminant muscle since grass silage is rich in C18:3n-3. The first objective of this experiment was to investigate the relationship between an increase in the dietary supply of C18:2n-6 from sunflower oil (SFO) and conjugated linoleic acid (CLA) concentration in the muscle tissue of beef cattle. The second objective was to investigate the effect of the basal forage type on the muscle fatty acid composition and its response to increasing inclusion of SFO. One hundred and five heifers were blocked according to initial bodyweight and assigned to one of seven silage treatments. The silage treatments were: (1) grass silage (GS), (2) whole crop wheat silage with 38% dry matter (DM) (W1), (3) GS and W1 at a ratio of 1:2 (DM basis) (W1GS) (4) GS and W1 at a ratio of 2:1 (DM basis) (GSW1), (5) whole crop wheat silage with 52% DM (W2), (6) GS and W2 at a ratio of 1:2 (DM basis) (W2GS), (7) GS and W2 at a ratio of 2:1 (DM basis) (GSW2). Within each silage treatment, 5 animals were assigned to one of three concentrate rations, differing in the content of SFO. The levels of inclusion of SFO in the concentrate were 0, 55, 110 g/kg concentrate. Inclusion of SFO in the diet led to an increase in the n-6:n-3 fatty acid ratio in muscle. In animals fed grass silage or mixed silages the n-6:n-3 ratio was lower in muscle compared with those fed whole crop wheat silages, with the exception of animals fed 55 g SFO/kg, for which feeding W1GS led to a higher ratio than W1. Other than the n-6:n-3 ratio there were no significant interactions between the effect of type of silage and the level of SFO on the concentration of fatty acids in intramuscular fat. Increasing the inclusion of SFO led to a linear increase in the CLAcis-9,trans-11 and PUFA concentration in intramuscular fat (P<0.001). This study confirmed the potential for modification, and improvement from a human health perspective, of the fatty acid composition of beef muscle by dietary manipulation. PMID- 22062991 TI - Profiles of water content, water activity and texture in crusted dry-cured loin and in non-crusted dry-cured loin. AB - This study compares the profiles of water activity (a(w)), water content (X) and texture in loin with crusted surface versus those profiles in loin without crust, and establishes a mathematical model able to describe hardness based on a(w) and/or X. Two loins (m. longissimus dorsi) were dry-cured, aged and then each one was divided into four pieces. Two of them were dried at 15+/-2 degrees C, 50+/ 3% RH (CL treatment) and the other two were dried at 2+/-2 degrees C, 80+/-3% RH (NCL treatment). The pieces of CL were dried under more severe conditions in order to develop a crust on the surface. Three-millimetre thick slices were taken from the most external part towards the inner part. The slices were prepared (10*10*3 mm) for texture profile analysis (TPA). Measurements of a(w) and X were carried out on each slice. Variance analyses and non-linear regression analyses were performed to create a model for loin hardness prediction through X and/or a(w) and a linear regression model for cohesiveness and springiness. CL loins showed a higher hardness and chewiness and lower cohesiveness at the surface (3 mm thickness) than the NCL loins. Hardness and chewiness, fitted with a non linear model, were better described by X than by a(w). Springiness showed a low relationship with X and a(w). The on-line monitoring of X and a(w) at the surface of the product would enable an estimation of the profiles of water content, a(w) and texture and it could be, therefore, a useful tool to avoid crusting. PMID- 22062992 TI - A comparison between two methods (Warner-Bratzler and texture profile analysis) for testing either raw meat or cooked meat. AB - Two methods for assessing texture characteristics of meat (Warner-Bratzler (WB) - and texture profile analysis (TPA)), both performed either on raw or on cooked meat, were tested in 96 samples of m. longissimus dorsi muscle of eight heifers and eight bulls, aged 1, 3 or 6 days post-mortem. A sensory analysis was also performed on 96 samples. Sensory variates were predicted by instrumental variates as follows: hardness was better predicted by TPA than by WB; springiness was only predicted by WB; juiciness was only significantly predicted by TPA; greasiness was always poorly predicted, but the prediction was better with TPA, and the number of chewings was also better predicted with TPA. Results suggested the convenience of performing a TPA for assessing meat texture as, in cooked meat, only TPA furnished highly significant correlations for hardness, for juiciness and for the number of chewings. Although WB could predict hardness and springiness, only the equation for the prediction of the number of chewings was useful (r(2)=0.171, P<0.004). It seems that texture parameters, assessed by a TPA and performed on cooked meat, are the best predictors of sensory texture in bovine meat. PMID- 22062993 TI - Application of computer image analysis to measure pork marbling characteristics. AB - Sixty longissimus (L) muscle chops were selected according to marbling score in order to develop a technique for the quantitative description of marbling fat by means of computer image analysis (CIA) and study its relationship with intramuscular fat content and shear force variation in pork. L muscle samples were taken from gilts belonging to three genetic lines differing in carcass leanness, namely Large White (LW), Meishan-derived dam line (M) and Synthetic Genex 3000 (SG). SG gilts had leaner loins (P<0.001) than LW and M. However, the SG loins were more marbled (P<0.001) and had higher IMF content. In addition, CIA analysis showed that marbling fat was finer and better distributed in the SG line. CIA marbling characteristics were significantly correlated with both IMF content (P<0.001) and shear force values (P<0.05) demonstrating the reliability of this technique to assess the contribution of marbling characteristics to variations in pork eating quality. PMID- 22062994 TI - Performance of Cinta Senese pigs and their crosses with Large White. 1 Muscle and subcutaneous fat characteristics. AB - Twenty-nine Cinta Senese (CS), 29 Large WhitexCinta Senese (LWxCS) and 12 Large White (LW) pigs were reared indoors and fed a commercial mixture. After slaughter (at avg. weight of 136, 139, 155 kg for CS, LWxCS, LW, respectively), a portion of the loin (sample cut) was dissected into lean and Longissimus lumborum (LL), intermuscular fat and bone. Chemical and physical analyses were conducted on LL. Chemical composition and fatty acid profile were determined on the outer layer of backfat. CS pigs had the highest percentage of bone and the lowest of lean in the sample cut, LWxCS showing intermediate values between parental breeds. In LL, CS showed lower moisture (73.23% vs. 74.28%) and higher fat content (3.19% vs. 0.87%) than LW; pH(24) was higher in CS (5.78) than in LWxCS (5.67) and LW (5.50); meat was more red in CS and LWxCS than in LW; CS showed higher water holding capacity than LW, with LWxCS at an intermediate position; raw meat was tougher in CS than in LW, but differences disappeared after cooking. In backfat CS had lower moisture (6.5% vs. 6.9% and 7.8%) and higher lipid content (81.4 vs. 78.1 and 77.5%) than LWxCS and LW; concerning fatty acid composition, CS showed less SFA (saturated fatty acids; 36.2% vs. 37.12% and 37.7%) than the other two genotypes, and, together with LWxCS, less PUFA (polyunsaturated fatty acids; 10.4% and 10.2% vs. 11.1%) and more oleic acid (50.3% and 49.8% vs. 48.5%) than LW. Overall, evidence of additive genetic effects was present for most qualitative parameters with crosses showing intermediate values between parental breeds. PMID- 22062995 TI - The effects of region and gender on the fatty acid, amino acid, mineral, myoglobin and collagen contents of impala (Aepyceros melampus) meat. AB - The effects of sex and region on the fatty acid profile, mineral contents, collagen and myoglobin contents of impala (Aepyceros melampus) meat were investigated. The study was conducted in the Limpopo Province of South Africa where impala were sampled from two separate regions. Female animals at Mara showed higher levels (P<0.05) of saturated (SFA), and mono-unsaturated fatty acids (MUFA) in their tissues than the male animals. The females at Musina also showed a tendency (P<0.10) towards higher levels of SFA and MUFA than the males. Males from both regions showed higher levels (P<0.05) of poly-unsaturated fat than the females. Myristic, palmitic and stearic acid made up the greatest proportion of the SFA component for the males and females from both regions. Oleic acid represented the largest component of the MUFA, with the Mara animals showing higher levels than the Musina animals. alpha-linoleic, gamma-linoleic, and linolenic acid made up the largest proportions of the poly-unsaturated component for both of the regions. Neither region nor sex had any influence on the amino acid content of the meat. The male animals at Mara had lower (P<0.05) myoglobin contents than the females for that region. Region had no effect on the myoglobin content of the meat. No significant sex or regional differences were found in the hydroxyproline and collagen contents of the meat (P>0.05). Regional differences (P<0.05) were found in the amounts of phosphorous and calcium present in the meat. The male animals at Mara were found to have higher levels of zinc than the females. PMID- 22062996 TI - Microbiological contamination of cattle and pig carcasses at five abattoirs determined by swab sampling in accordance with EU Decision 2001/471/EC. AB - A total of 800 cattle carcasses (abattoir A: n=200; B: n=150; C: n=150; D: n=150, E: n=150) and 650 pig carcasses (abattoir A: n=200; B: n=150; C: n=150; D: n=150) were examined at five Swiss abattoirs with an annual slaughtering capacity >10 million kg. Weekly, 10 cattle and 10 pig carcasses were sampled at four sites by the wet-dry double swab technique. From each carcass the samples were pooled and examined for total viable counts (TVC) and Enterobacteriaceae. At the abattoirs, mean log TVCs from cattle carcasses ranged from 2.1 to 3.1 cm(-2) and those from pig carcasses from 2.2 to 3.7 cm(-2). Daily TVC mean log values showed significant differences between abattoirs (P<0.05), whereas no significant differences were detected between animal species. On average, Enterobacteriaceae were detected (i) in low counts, (ii) on 31.0% of cattle and on 20.2% of pig carcasses, and (iii) more frequently and in higher counts on cattle than on pig carcasses (P<0.05). Data from this study indicate that the wet-dry double swab technique is suitable to determine microbiological contamination of cattle and pig carcasses in accordance with EU Decision 2001/471/EC. For samples obtained by the non-destructive technique from cattle and pig carcasses, the following microbiological performance criteria are proposed: Daily mean log values are acceptable, marginal, and unacceptable for TVC when they are <3.00, 3.00-4.00, >4.00 cm(-2), and for Enterobacteriaceae when they are <1.00, 1.00-2.00, and >2.00 cm(-2). However, such values have to be seen merely as baselines. It is important to implement a monitoring system based on abattoir-specific data and criteria as permitted by quality control chart methods. PMID- 22062997 TI - Prediction of horse carcass composition using linear measurements. AB - An analysis of meat quality performed on 107 horses showed that there are significant relationships between some linear measures of carcasses and the irrespective tissue contents. Thus, there is some potential for fat quantity estimation on the basis of nape fat thickness. The equation for the assessment of fat percentage in the carcass contains one variable, i.e., nape fat thickness only. However, even in this case the obtained multiple correlation coefficient was high, R=0.86 and the estimation error was at the level of 2.5%. As a consequence, the estimation of fat deposits in carcasses may be made more objective, and the measurement of nape fat thickness may be applied for the assessment of fat in the live animal. PMID- 22062998 TI - Breed, slaughter weight and ageing time effects on sensory characteristics of lamb. AB - The longissimus lumborum (right and left) from 180 entire male lambs were tasted by a nine-member trained taste panel. The samples were from lambs from three Spanish breeds; Rasa Aragonesa (local meat breed), Churra (local dairy breed) and Spanish Merino. Within breed, three slaughter live weights were considered (10 12, 20-22 or 30-32 kg) and meat was aged in a vacuum package for 1, 2, 4, 8 or 16 days. Panellists assessed a total of eight descriptors. Lamb odour and lamb flavour intensities increased with slaughter weight. However, fat flavour intensity was significantly influenced by breed, with the highest score for Rasa Aragonesa. Off-flavour intensity was influenced by breed and ageing, with higher scores for Rasa Aragonesa and longer ageing times. Tenderness and juiciness were influenced by all three effects (P?0.001, each) and there was a significant interaction between breed and slaughter live weight. Meat was juicier and more tender in the lightest Churra lambs, and in the Spanish Merino lambs for the heavier weight animals. Tenderness and juiciness increased with ageing. The best quality flavour was for the Spanish Merino and the intermediate and heavier lambs. PMID- 22062999 TI - Calpain system in vitro activity and myofibril fragmentation index in fallow deer (Dama dama): effects of age and supplementary feeding. AB - Calpain system (MU- and m-calpain, calpastatin) and myofibril fragmentation index (MFI) were analysed on muscle longissimus thoracis et lumborum of 16 male fallow deer, half 18- and half 30-month-old, slaughtered after a 4-month feeding trial on pasture alone or with concentrate supplement. Diet did not produce any difference on the measured variables. The muscle of the elder deer had a higher calpastatin level 6 h post-mortem (136.0 vs. 99.7 units/50 g, for the 30- and 18 months-old, respectively), and a lower MFI value, particularly 24 h post-mortem (71.1 vs. 89.1). This is in agreement with previous data showing tougher meat from 30-month-old animals. PMID- 22063000 TI - A research note on predicting the carcass yield of Korean native cattle (Hanwoo). AB - This study developed a new equation to predict the carcass yield of Hanwoo cattle, as well as re-evaluating a previous prediction equation. Experimental animals comprised 79 cows, 79 steers, and 79 bulls. A stepwise model selection was performed to determine the most practical carcass traits for predicting the yield. Cold carcass weight (CW), backfat thickness (BFT), and ribeye area (REA) accounted for 52% variation in yield, and these were determined as the final parameters. When the kidney, pelvic, and heart fat were included in the model, this increased the percentage variation explained (R(2)) by 4%. To compare the newly developed equation (Yield=64.65-0.0198*CW-5.2264*BFT+0.1339*REA) and the previously used one, carcass yields of 377,048 industrial animals (145,695 cows, 225,926 bulls, and 5427 steers) were assessed. For the newly developed equation, the mean difference between experimental animals industrial animals differed only by 1.99-2.68% for all sex groups. In the case of the previous prediction equation, the mean difference ranged from 6.06% for bulls to 11.05% for steers. The results demonstrated that the prediction equation should use a mixture of sex and market weight groups. The results also support our decision to use the newly developed model in predicting the yield of Hanwoo. PMID- 22063001 TI - Polypeptide conjugates of D-penicillamine and idarubicin for anticancer therapy. AB - We investigated anticancer therapy with a novel combination of D-penicillamine (D pen) and Idarubicin (Ida) in a synthetic dual drug conjugate (DDC). D-pen and Ida were covalently linked to poly(alpha)-L-glutamic acid (PGA) via reducible disulfide and acid-sensitive hydrazone bonds, respectively. The DDCs showed cell uptake and sustained release of the bound drugs in conditions mimicking the intracellular release media (10mM glutathione and pH 5.2). The in-vitro cytotoxicity of DDCs was comparable to unconjugated Ida in several sensitive and resistant cancer cell lines and correlated with the rate of cell uptake. In a single equivalent-dose pharmacokinetic study, DDCs enhanced the drug exposure by 7-fold and prolonged the plasma circulation half-life (t(1/2)) by 5-fold over unconjugated Ida. The therapeutic index of DDCs was 2-3-fold higher than unconjugated drugs. DDCs caused 89% tumor growth inhibition compared to 60% by unconjugated Ida alone and led to significant enhancement in the median survival (17%) of athymic nu/nu mice bearing NCI-H460 tumor xenografts. PMID- 22063002 TI - Polyelectrolyte LbL microcapsules versus PLGA microparticles for immunization with a protein antigen. AB - The transition from organism-based traditional vaccines to the use of safer subunit vaccines has implemented the use of adjuvants to enhance immunogenicity. This study compares the potential of two types of polymeric microparticles as delivery systems for the model antigen ovalbumin. The delivery systems encompassed polyelectrolyte microcapsules, assembled via Layer-by-Layer technology, and PLGA microparticles fabricated by spray-drying. Mice were immunized subcutaneously either by a single injection or by two injections separated by four weeks with an equivalent dose of the OVA-loaded particles. Both particulate formulations mediated high, long-term IgG(1) responses whereas the IgG(2c) titers remained low. Additionally, Th1 and Th2 phenotype immune responses against OVA were assessed by quantifying the production of cytokines in CD4+ T cells derived from the spleens of immunized mice at 6 months after the first injection. Immunization with particulate formulations led to significantly increased IL-2, IL-4, IL-10 and IFN-gamma production by splenic CD4+ T-cells compared to control animals. LbL microcapsules and PLGA microparticles generated strong immune responses in vivo, characterized by a mixed Th1/Th2 type response with predominance of Th2 immunity. Both particulate formulations elicited a comparable type of immune response and appear to be promising for antigen delivery. PMID- 22063003 TI - Photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres: A platform for near-infrared light-trigged drug release. AB - Photothermal ablation (PTA) is an emerging technique that uses near-infrared (NIR) laser light-generated heat to destroy tumor cells. However, complete eradication of tumor cells with PTA is difficult because of uneven heat distribution in the treatment volume. We hypothesized that combining PTA with chemotherapy using a single multifunctional nanoconstruct that mediates simultaneous photothermal cell killing and drug release (photothermal chemotherapy) would result in enhanced antitumor activity and reduced toxicity compared to chemotherapy alone. Doxorubicin (DOX) was loaded to hollow gold nanospheres (HAuNS) coated with polyethylene glycol (PEG). The pharmacokinetics and biodistribution of both DOX and HAuNS in the resulting nanoconstruct, DOX@PEG HAuNS having different DOX:PEG:HAuNS ratios, were evaluated using dual isotope labeling techniques. The antitumor activity of DOX@PEG-HAuNS with DOX:PEG:HAuNS weight ratio of 1:3:1 (NP3) in combination with NIR laser was studied in vitro and in vivo using human MDA-MB-231 breast cancer and A2780 ovarian cancer cells. In vitro, NP3 mediated PTA of both cancer cells and DOX release upon NIR laser treatment. In vivo, NP3 showed slower clearance in blood and greater accumulation in tumors than free DOX. NP3-plus-NIR laser demonstrated greater antitumor activity than free DOX, NP3, or liposomal DOX. Moreover, NP3 displayed significantly decreased systemic toxicity compared to free DOX or liposomal DOX. Enhanced antitumor effect with NP3-plus-laser can be attributed to both the cytotoxic effect of DOX released from NP3 and the photothermal effect mediated by HAuNS. Slow release of DOX from NP3 in normal tissues contributed to reduced systemic toxicity. Photothermal-chemotherapy exemplified by a single-agent nanoconstruct NP3 is a promising approach to anticancer therapy. PMID- 22063004 TI - Rapid kinetics to peak serum antibodies is achieved following influenza vaccination by dry-coated densely packed microprojections to skin. AB - A rapid time to peak serum antibody response following vaccination is particularly important for influenza: the time window between the availability of appropriate antigen and the start of the seasonal epidemic is very short. In this paper, influenza vaccine was delivered to both the epidermis and dermis of mouse skin using densely packed microprojection arrays for vaccination. We found that, after vaccination, around 75% and 90% of the delivered influenza vaccine migrated away from the ear skin within just 2 days and 1 week - respectively. And the time to peak serum antibody response was as early as 2 weeks. This result matches the kinetics achieved by intramuscular injection of liquid vaccine to muscle. Thus, we demonstrate that skin delivery of small vaccine volumes discretely by thousands of densely packed microprojections neither induces delay in kinetics nor interferes with the long-lasting antibody response; compared to conventional intramuscular injection. PMID- 22063005 TI - Biodegradable polymersomes as carriers and release systems for paclitaxel using Oregon Green(r) 488 labeled paclitaxel as a model compound. AB - Oregon Green(r) 488 labeled paclitaxel (Flutax) loaded biodegradable polymersomes (Flutax-Ps) based on methoxy poly(ethylene glycol)-b-poly(d,l-lactide) (mPEG PDLLA), methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone) (mPEG-PCL) or a mixture of the block copolymers (50:50, w/w) were prepared (abbreviated as Flutax-Ps (L), Flutax-Ps (C) and Flutax-Ps (LC), respectively). For the formation of the Ps, the corresponding block copolymers and Flutax were dissolved in THF and the THF solution was injected into an aqueous phase. Flutax-Ps with a size less than 150nm were obtained, which had Flutax entrapment efficiencies higher than 55% (polymer concentration: 1mg/ml; Flutax concentration up to 100MUg/ml). A sustained and complete release of Flutax was observed for Flutax-Ps (L) over one month with no initial burst. Flutax was released much slower from Ps (C) than from Ps (L) (49.9% after one month), which is probably due to differences in the crystallinity and rate of degradation of the consisting copolymers. The release rate of Flutax from Ps (LC) was in between those of Ps (L) and Ps (C). The in vitro cytotoxicity of Flutax-Ps (L) using cultured SKBR3 breast cancer cells was compared with that of empty Ps (L) and a Cremophor(r) EL/ethanol formulation (50:50, v/v) with Flutax (FCE) or without Flutax (CE). At a Flutax concentration of 5MUg/ml, about 67% reduction in the viability of SKBR3 cells was observed for Flutax-Ps (L) after 3days exposure, while the FCE formulation reduced the cell viability for more than 90% under the same conditions. Empty Ps (L) showed a low toxicity of about 10% and the CE formulation exhibited a cytotoxicity higher than 54% without Flutax, indicating that the high reduction in SKBR3 cell viability for FCE is associated with the toxicity of the Cremophor(r) EL formulation. PMID- 22063006 TI - Characterization of novel spray-dried polymeric particles for controlled pulmonary drug delivery. AB - Numerous studies have addressed the controlled pulmonary drug delivery properties of colloidal particles. However, only scant information on the potential of spray drying for submicron particle preparation is available. By exploiting the advantages of spray-drying, the characteristics of submicron particles can be optimized to meet the requirements necessary for lung application. Submicron particles were prepared from organic poly(d,l-lactide-co-glycolide) (PLGA) solutions, and composite particles were spray-dried from aqueous PLGA nanosuspensions. The feed concentration, as well as the spray-mesh diameter influenced the resulting particle sizes. Nanoparticles were virtually unaffected after spray-drying. The aerodynamic characteristics of both particle species revealed aerosol particle sizes suitable for deposition in the deep lungs (<=4MUm). While the entrapped drug was released within ~90min from the composite particles, extensive drug retardation (~480min) was observed for PLGA particles spray-dried from organic solution. These results suggest that nanospray-drying is a convenient method to prepare submicron, controlled drug delivery vehicles useful for pulmonary application potentially allowing access to alveolar tissue. PMID- 22063007 TI - Low temperature fabrication of biodegradable sugar glass microneedles for transdermal drug delivery applications. AB - Transdermal drug delivery is limited by the barrier properties of the outer skin layer. Microneedles (MNs) effectively circumvent the skin barrier to offer this route as a potential alternative to oral and parenteral delivery of therapeutics. Biodegradable microneedles offer particular advantages however processing commonly requires elevated temperatures that may adversely affect heat-labile molecules and macromolecules. In this study, solid amorphous sugar glasses containing low residual quantities of water were created by dehydration of trehalose and sucrose sugar combination solutions. Biodegradable sugar glass MNs were fabricated following optimisation of a simple and novel low temperature vacuum deposition micromoulding methodology. These had absolute morphological fidelity to silicon master structures and demonstrated sufficient structural rigidity to efficiently penetrate excised human breast skin. Sugar glass MNs incorporating a marker compound dissolved rapidly and completely in situ releasing dye into deeper skin layers. The biological activity of a model macromolecule was partially retained over extended storage following incorporation into sugar glass. This is the first demonstration that MNs created from amorphous sugar glasses can be used for incorporating and delivering molecules, and potentially biologically active macromolecules, via the transdermal route. PMID- 22063008 TI - Factors of significance for pork quality-a review. AB - This paper reviews current knowledge about factors of importance for pork quality with special emphasis on technological quality attributes. It is evident that production and slaughter factors can be used to control technological quality traits. However, most of the present knowledge is based on studies investigating the influence of a single or at the most two factors. This survey reveals that: Most important, an understanding of how production and slaughter factors interact in relation to pork quality is a must to give the maximum number of tools to control pork quality and hereby meat quality demands of tomorrow. -The existence of a new genetic pool (elimination of the halothane and RN(-) genes in the commercial pig populations of tomorrow) force the meat science into a renaissance, as the influence of production and slaughter factors on pork quality may be fundamentally different in this new genetic pool. -A basic understanding on how muscle glycogen stores are influenced by genotype and feeding regime and the interaction with pre-slaughter handling might be the next major breakthrough in controlling technological pork quality. -Introduction of new production systems claim parallel studies to prevent unforseen negative effect on quality. A holistic approach is needed to give an overall understanding of the influence of production, peri and post mortem factors on pork quality. PMID- 22063009 TI - Stable isotope ratio analysis for authentication of lamb meat. AB - The effectiveness of the analysis of stable isotope ratios ((13)C/(12)C and (15)N/(14)N) in fractions of lamb meat, measured by isotope ratio mass spectrometry, was evaluated as a method of feeding and geographical origin authentication. Analyses were carried out on meat from 12 lamb types, produced in couples in six European countries (country of origin, CO) and divided in three groups according to the feeding regime during their finishing period: suckled milk only, pasture without any solid supplementation and supplementation containing maize grain (feeding regime, FR). These analyses were made on two samples of longissimus thoracis muscle, taken from the 13th rib section of the left side of two different lambs, randomly chosen between the 120 selected to represent each lamb type. delta(13)C values varied significantly in different meat fractions, the difference being higher in protein than in fat (average difference 5.00/00). However, the pairs delta(13)C values of crude fat and protein were highly correlated (r=0.976) and affected by lamb type in a similar fashion, mainly reflecting animals' feeding regime. Even delta(15)N values of meat protein fraction showed significant differences between lamb types, not dependant on the feeding regime. In fact, lambs fed on similar diets, but in different countries, gave meat with different (15)N relative abundances. These findings provide the possibility of discriminating lamb types within the same feeding regime. Canonical discriminant analysis was carried out to evaluate whether lamb meat from different CO or FR or CO*FR interaction could be mathematically distinguished by its stable isotope ratios. On the basis of CO, the corrected empirical allocation of 79.2% of the initial observations and the corrected cross-validation of two thirds of the individual meat samples was obtained. FR gave better results: 91.7% of the individual meat samples was both correctly allocated and cross-validated, indicating the high potential of stable isotope ratio analysis as a tool for lamb diet characterisation. The most satisfactory classification attained, using K-means clustering technique and canonical discriminant analysis, enabled a good resolution of six CO*FR groups of lamb types: Icelandic fed on pasture; British and French grazing; Italian; suckled and Karagouniko concentrates finished; French Lacaune; Ternasco de Aragon. It was concluded that multielement stable isotope analysis may be considered promising for the reliable evaluation of lamb meat authenticity, in the same way as for wine, fruit juice, honey and dairy products. PMID- 22063010 TI - Artificial intelligence techniques point out differences in classification performance between light and standard bovine carcasses. AB - The validity of the official SEUROP bovine carcass classification to grade light carcasses by means of three well reputed Artificial Intelligence algorithms has been tested to assess possible differences in the behavior of the classifiers in affecting the repeatability of grading. We used two training sets consisting of 65 and 162 examples respectively of light and standard carcass classifications, including up to 28 different attributes describing carcass conformation. We found that the behavior of the classifiers is different when they are dealing with a light or a standard carcass. Classifiers follow SEUROP rules more rigorously when they grade standard carcasses using attributes characterizing carcass profiles and muscular development. However, when they grade light carcasses, they include attributes characterizing body size or skeletal development. A reconsideration of the SEUROP classification system for light carcasses may be recommended to clarify and standardize this specific beef market in the European Union. In addition, since conformation of light and standard carcasses can be considered different traits, this could affect sire evaluation programs to improve carcass conformation scores from data from markets presenting a great variety of ages and weights of slaughtered animals. PMID- 22063011 TI - Whey and soy protein hydrolysates inhibit lipid oxidation in cooked pork patties. AB - Pork patties containing 1.5% NaCl and 2% hydrolyzed whey protein isolate (WPI, 1 h with flavourzyme or 6 h with protamex) or soy protein isolate (SPI, 0.5 h with chymotrypsin or flavourzyme) were cooked to 70 degrees C and subsequently stored at 4 degrees C up to 7 days. Lipid oxidation in patties during storage was analyzed by measuring the concentration of conjugated dienes (CD) and thiobarbituric acid-reactive substances (TBARS). Intact WPI and SPI, and their hydrolysates, were all inhibitory of oxidation (P <0.05) in cooked patties, with SPI being slightly more effective than WPI. Hydrolysis with protamex augmented the antioxidative activity (CD, TBARS) of WPI. Hydrolysis with either chymotrypsin or flavourzyme improved the ability of SPI to retard CD formation but did not delay the production of TBARS in stored pork patties. PMID- 22063012 TI - Influence of pH and temperature on growth and bacteriocin production by Leuconostoc mesenteroides L124 and Lactobacillus curvatus L442. AB - The aim of this study was to investigate the relationship between the microbial growth, the bacteriocin production and the effect of pH and temperature on the occurrence and the concentration of the maximum activity, to optimize the bacteriocin synthesis during the growth cycle. Two bacteriocins produced by lactic acid strains Leuconostoc mesenteroides L124 and Lactobacillus curvatus L442 were studied. A slight increase of the final biomass resulted in the improvement of the bacteriocin activity in the growth medium under controlled pH (5.0 and 5.5). Temperature and pH had a significant effect on the production of the two bacteriocins and was enhanced by the relatively low growth rates. The optimum production conditions of the bacteriocins did not coincide with those for growth. The optimum pH and temperature values for growth were 6.0-6.5 and 30 degrees C and for bacteriocin production were 5.5 and 25 degrees C. PMID- 22063013 TI - Injection of sodium chloride, sodium tripolyphosphate, and sodium lactate improves Warner-Bratzler shear and sensory characteristics of pre-cooked inside round roasts. AB - Paired inside rounds (n=30 pairs) were removed from randomly selected USDA Select quality grade carcasses to examine the effects of injecting a solution of sodium lactate, sodium tripolyphosphate, and sodium chloride on Warner-Bratzler shear force, cooking loss, lipid oxidation, and sensory characteristics of pre-cooked beef. Injected treatments were more tender (P<0.05) than control products, as measured by Warner-Bratzler shear force and consumer sensory panel ratings. Injected treatments had lower (P<0.01) cooking and re-heating loss percentages when compared to control samples. Lipid oxidation in injected treated samples was significantly reduced as compared to control meat samples. Results of lipid oxidation also revealed that 14-day samples were less (P<0.01) than 0-day samples. Results of this experiment have shown that injection of this solution enhanced sensory panel characteristics, and decreased WBS values and cooking loss. PMID- 22063014 TI - Dietary vitamin E supplementation effects on the color and sensory characteristics of enhanced beef steaks. AB - The objective of this study was to evaluate the effects of dietary vitamin E supplementation on characteristics of enhanced beef cuts during retail display. Twelve steers were fed either a control (E-) diet or a diet supplemented with dl alpha tocopheryl acetate (E+) for 117 days prior to slaughter. Paired strip loins, clods, and inside rounds served as the control (C) or were pumped (P) to 110% of raw weight to contain 0.4% sodium chloride and 0.4% phosphate on a finished weight basis. Steaks were cut (2.5 cm) for sensory evaluation and retail display. No flavor or texture differences existed in strip steaks due to vitamin E. Enhanced steaks were more tender, juicy and salty than controls, however they discolored more rapidly than did controls. Steaks from supplemented cattle were slightly, but significantly, less discolored, indicating that vitamin E may provide some improvements in color stability of enhanced meat products. Vitamin E supplementation may improve short term color stability (up to 2 days in display) of retail beef enhanced by injection of a salt-phosphate solution. PMID- 22063015 TI - Differences in meat quality between organically and conventionally produced pigs. AB - This study compared organic pig meat production with conventional production with regard to carcass- and meat quality traits. 80 crossbred female and castrated male pigs were used [(Swedish Landrace * Swedish Yorkshire) * Hampshire] of which 40 were raised under organic conditions and the other 40 were raised in a conventional production system. The organic pigs were raised outdoors in one large group following the regulations for organic standards. The conventionally raised animals were kept indoors in groups of eight and were given a conventional feed mixture. It was found that meat of organically raised non-carriers of the RN(-) allele was of poorer quality (higher drip loss and increased shear force values) compared with meat from the other animals. The RN genotype had a relatively small effect on carcass and technological traits in this study. The sex of the animals affected carcass traits. PMID- 22063016 TI - Effects of calcium salts on beef longissimus quality. AB - The objective of this research was to evaluate the effects of injection marination with calcium salts on beef longissimus quality traits. Strip loins were injected (11% by weight) with distilled water or a 0.1, 0.2, or 0.3 M solution of calcium ascorbate, calcium chloride, or calcium lactate. Non-injected loins served as controls. Visual and instrumental color evaluations indicated that calcium ascorbate accelerated myoglobin oxidation, and increasing molar concentration of any calcium salt caused faster (P<0.05) discoloration. Aerobic microbial plate counts were lower (P<0.05) for treatments containing calcium lactate than those with calcium chloride or calcium ascorbate. Calcium ascorbate inhibited lipid oxidation whereas calcium lactate and calcium chloride appeared to be pro-oxidants of lipid oxidation. No differences for Warner-Bratzler shear force or sensory panel tenderness were found among the calcium salts; however, 0.3 M treatments had lower shear values and were judged more tender than 0.1 M treatments. Calcium ascorbate and calcium chloride treatments resulted in less (P<0.05) beef flavor and more (P<0.05) off-flavors than calcium lactate treatments. In addition, 0.1 M treatments had higher (P<0.05) beef flavor scores while 0.3 M treatments had higher (P<0.05) off-flavor scores. Considering the effects on color life, microbial inhibition, shear force, and sensory traits, we recommend injecting beef longissimus with a 0.1 M solution of calcium lactate to enhance both uncooked and cooked quality. PMID- 22063017 TI - Fatty acid profile, cholesterol content and tenderness of ostrich meat as influenced by age at slaughter and muscle type. AB - Ten Blue Neck ostriches were used to study the effect of age at slaughter (10-11 and 14-15 months) and muscle on fatty acid profile, cholesterol content and texture of meat. Fatty acid profile of ostrich meat was significantly affected by age at slaughter (P<0.001) and muscles (P<0.001). Different age at slaughter (10 11 vs. 14-15 months) produced an increase of P/S ratio (P<0.001), total saturated (P<0.05) and monounsaturated (P<0.001) fatty acids. The highest percentage of saturated and monounsaturated fatty acids were found in M. iliofibularis (P<0.001), whereas M. gastrocnemius showed the highest content of polyunsaturated fatty acids (P<0.001). Analysis of variance of data on cholesterol content (mg/100 g of meat) showed no significant effects of age at slaughter and muscle location. No effect of age on shear values was observed, whereas sensory panellists scored meat from younger birds as more tender (P<0.001). Both instrumental and sensory evaluation indicated that meat from M. iliofibularis was more tender (P<0.001). PMID- 22063018 TI - Effect of dietary vitamin E supplementation on textural and aroma attributes of enhanced beef clod roasts in a cook/hot-hold situation. AB - The objective of this study was to evaluate the effects of supplementing vitamin E into the diets of finishing cattle on quality characteristics of beef pumped with a phosphate/salt solution (enhanced) the cooked and held in a simulated foodservice situation. Twelve steers were fed either a control (E-) diet or a diet supplemented with dl-alpha-tocopheryl-acetate (E+). Paired clod roasts were either used as controls (C) or were pumped (P) to 110% of raw weight to contain 0.4% sodium chloride and 0.4% phosphate in the finished product. Following injection, clods were allowed to equilibrate then frozen. A flavor profile panel evaluated texture attributes and aroma characteristics of roasts immediately after cooking and after 1 and 2 h of hot-holding. Pumping improved taste and textural attributes of the hot-held clod roasts. Dietary vitamin E supplementation reduced thiobarbituric acid reactive substances (TBARS) from ~0.61 to ~0.42, but over the 2-h time period, did not significantly improve aroma quality of beef roasts. PMID- 22063019 TI - Partial substitution of pork backfat with extra-virgin olive oil in 'salami' products: effects on chemical, physical and sensorial quality. AB - The effects on chemical, physical and sensory quality of the partial substitution of pork backfat with extra-virgin olive oil were studied in 'salami' products. Four 'salami' formulations, with 15% total fat, were prepared, in which 0, 33.5, 50 and 66.5% of pork backfat was substituted with extra-virgin olive oil. The partial pork backfat substitution with extra-virgin olive oil did not substantially affect the chemical, physical and sensorial characteristics of products, with the exception of water activity and texture. With regard to both oxidation and loss of organoleptic quality, the addition of extra-virgin olive oil, rich in mono-unsaturated fatty acids, did not decrease the shelf-life. The difference between samples with and without extra-virgin olive oil was a piquant note detected in the oil-added 'salami'. The formulation with 5% olive oil, corresponding to 33.3% substitution of pork backfat with olive oil, was judged best of all formulations. The results show that it is possible to produce this type of product, of good taste, similar to the traditional one, but with healthier features. PMID- 22063020 TI - The use of computational approaches in inhaler development. AB - Computational Fluid Dynamics (CFD) and Discrete Element Modelling (DEM) studies relevant to inhaled drug delivery are reviewed. CFD is widely used in device design to determine airflow patterns and turbulence levels. CFD is also used to simulate particles and droplets, which are subjected to various forces, turbulence and wall interactions. These studies can now be performed routinely because of the availability of commercial software containing high quality turbulence and particle models. DEM allows for the modelling of agglomerate break up upon interaction with a wall or due to shear in the flow. However, the computational cost is high and the number of particles that can be simulated is minimal compared with the number present in typical inhaled formulations. Therefore DEM is currently limited to fundamental studies of break-up mechanisms. With decreasing computational limitations, simulations combining CFD and DEM that can address outstanding issues in agglomerate break-up and dispersion will be possible. PMID- 22063021 TI - Host factors affecting antiepileptic drug delivery-pharmacokinetic variability. AB - Antiepileptic drugs (AEDs) are the mainstay in the treatment of epilepsy, one of the most common serious chronic neurological disorders. AEDs display extensive pharmacological variability between and within patients, and a major determinant of differences in response to treatment is pharmacokinetic variability. Host factors affecting AED delivery may be defined as the pharmacokinetic characteristics that determine the AED delivery to the site of action, the epileptic focus. Individual differences may occur in absorption, distribution, metabolism and excretion. These differences can be determined by genetic factors including gender and ethnicity, but the pharmacokinetics of AEDs can also be affected by age, specific physiological states in life, such as pregnancy, or pathological conditions including hepatic and renal insufficiency. Pharmacokinetic interactions with other drugs are another important source of variability in response to AEDs. Pharmacokinetic characteristics of the presently available AEDs are discussed in this review as well as their clinical implications. PMID- 22063022 TI - Physicochemical and textural properties of ultrasound-degraded konjac flour and their influences on the quality of low-fat Chinese-style sausage. AB - Physical and textural properties of varying molecular-weight konjac gels made by ultrasonic degradation were compared and gels were processed into low-fat Chinese style sausages for the evaluation of textural and sensory characteristics. Results showed that as molecular weights decreased, storage modulus and loss modulus of konjac gels of varying molecular weights declined, indicating more elastic and viscous konjac gels. Shear values and textural springiness and cohesiveness of Chinese sausage were similar among all treatments. All treatments were found to have similar juiciness and overall acceptability scores. Results indicated that konjac gels with varying molecular weights could be used to partially replace pork fat to achieve similar textural properties. Incorporation of konjac gels with varying molecular weights at the current levels showed similar textural and sensory quality characteristics to the high-fat control, and contained less fat than traditional Chinese sausage. PMID- 22063023 TI - The intracellular distribution of small heat shock proteins in post-mortem beef is determined by ultimate pH. AB - This study analysed Longissimus dorsi muscles from 39 Angus or Angus*Limousin bulls to determine the small heat shock protein (sHSP) dynamics in beef aged at 15 degrees C. Using quantitative ELISA we determined that alpha beta-crystallin and HSP20 were present at higher levels in muscles from Angus bulls. sHSP levels peaked at 0.5 and 3h post-mortem for HSP20 and alpha beta-crystallin respectively. Intermediate pH (pH 5.7-6.3) beef had the highest level of alpha beta-crystallin expression at 3-6h post-mortem. Low pH (<5.7) meat had no detected soluble alpha beta-crystallin and had diminished HSP27 at 22h post mortem. The transition of sHSP between a soluble to an insoluble phase was demonstrated by pH titration of a sarcoplasmic fraction. The effect of ultimate pH upon sHSP distribution in post-mortem muscle may influence final meat quality characteristics. PMID- 22063024 TI - Dry versus wet aging of beef: Retail cutting yields and consumer palatability evaluations of steaks from US Choice and US Select short loins. AB - Paired beef short loins from US Choice (n=48) and US Select (n=48) carcasses were assigned to be dry or wet aged for 14, 21, 28 or 35d. After aging, short loins were processed to determine retail yields and processing times. Upon completion of cutting tests, steaks were served to consumers to assess palatability characteristics. Retail cutting tests showed that dry-aged short loins had reduced yields and increased cutting times when compared to wet-aged short loins. Consumers were unable to determine differences between dry- and wet-aged steaks and for aging periods; however, USDA quality grade had a significant impact on consumer perception of palatability attributes. PMID- 22063025 TI - Extraction of proteins from slaughterhouse by-products: Influence of operating conditions on functional properties. AB - This study investigated the extraction and functional properties of proteins from slaughterhouse by-products: pork lungs, beef lungs and mechanically deboned chicken meat (MDCM). The extraction yield was investigated as a function of pH, temperature and time. Membrane technology was used for purification of proteins from pork and beef lungs, while for MDCM a method based on PI was applied. In the three cases, yields of protein recovery were between 48 and 55% (w/w). The functional properties of the protein concentrates were compared to those of some commercial ingredients. Proteins from pork lungs and MDCM exhibited better gelling properties than egg white and beef plasma, while beef and pork lungs displayed very good emulsifying properties, similar to Na-caseinates. As the methods developed are easy to scale-up, the use of by-product proteins at industrial scale appears to be an interesting opportunity to obtain added value slaughterhouse by-products. PMID- 22063026 TI - Effects of oxygen concentration on the sensory evaluation and quality indicators of beef muscle packed under modified atmosphere. AB - Beef steaks are commonly displayed under high oxygen concentrations in modified atmosphere packs (MAP) in order to promote colour stability. Such conditions, however, may also cause quality deterioration through lipid oxidation and decreased tenderness. The objective of this study was to investigate the effects of oxygen concentration (0%, 10%, 20%, 50% and 80%) on the quality of MAP beef steaks (M. longissimus dorsi). Steaks were stored at 4 degrees C for 15 days and tested for lipid and protein oxidation, heme iron, colour, oxymyoglobin concentration, tenderness and sensory acceptability (up to day 12) for the resulting cooked meat. Sensory panellists expressed a preference for steaks stored in packs containing 50% oxygen, despite detecting oxidised flavours under these conditions. This could be the result of adaptation to, or familiarity with, oxidised flavours by panellists. PMID- 22063027 TI - Finishing steers with diets based on corn, high-tannin sorghum or a mix of both: Color and lipid oxidation in beef. AB - We tested the hypothesis that feeding high-tannin sorghum (HTS) to steers would produce beef more resistant to oxidative deterioration. We observed lower thiobarbituric acid-reactive substances (TBARS) in Gluteus medius of steers fed HTS before it was displayed (P=0.028), which could be explained by a reduced response to stress in these animals. While steers finished with corn and corn+HTS had elevated plasma cortisol at the end of the feeding period (P=0.047 and 0.093, respectively), animals fed HTS and corn+vitamin E did not. However, feeding HTS increased the rate of discoloration and TBARS accumulation after aerobic display of Longissimus lumborum and Gluteus medius. Diet did not affect the activity of oxidation-related enzymes and fatty acid composition of muscle. The accelerated rate of lipid oxidation during display of beef could be partially explained by a numerically lower concentration of tocopherols in the tissue. PMID- 22063028 TI - Impact of feeding and rearing systems of Iberian pigs on volatile profile and sensory characteristics of dry-cured loin. AB - The effect of growing pigs on free-range (FR) or in confinement with three different diets [acorn (A), acorn and grass (A-G) and formulated diet (FD)] on composition, volatile profile and sensory characteristics of dry-cured loin was studied. The FR, A and A-G diets, in comparison with FD, induce a higher alpha- and gamma-tocopherol concentration, which limits the TBARs values at 24h of air exposure. Sixty volatile compounds were identified in the headspace, including 14 aldehydes, 10 hydrocarbons, eight alcohols, five ketones, four furans, four pyrazines, four sulphur compounds, three acids, three esters, three phenols, one pyridine and one pyrrole. Volatiles from amino acid catabolism stressed the difference among batches FR being the batch with the highest level of these compounds. Products from FD showed the lowest fat content and L(*) value. FR loins obtained the highest scores for appearance, odour and flavour in the rank order test sensory analysis. PMID- 22063029 TI - Study of salting and post-salting stages of fresh and thawed Iberian hams. AB - Fresh raw material has been traditionally used to obtain dry-cured Iberian ham, although the use of thawed raw material is increasing. This type of raw material has been previously studied for dry-cured production employing White pigs, where the salting time has been reduced to reach similar NaCl concentrations. The aim of this work was the analysis of salting and post-salting stages of Iberian hams, employing fresh or thawed raw materials. The results showed that fresh Iberian hams had higher salt concentrations than thawed Iberian hams for the salting time ratio used, a ratio established to reduce the freezing/thawing effect that was previously observed working with White ham. This fact shows that the Iberian raw material in dry-cured ham manufacturing is less affected, by the freezing/thawing process than the White raw material. PMID- 22063030 TI - The impact of new generation pre-dressing medium-voltage electrical stimulation on tenderness and colour stability in lamb meat. AB - Previous work identified that a large number of domestic lamb carcases processed in Australia do not meet the recommended pH/temperature window during chilling. New medium voltage electrical stimulation technology has been developed to alleviate this problem. This study used an optimised setting (800mA with a pulse width 0.5ms) to evaluate the effects on meat quality with a focus on tenderness and meat colour. In total 40 (electrically stimulated) and 40 (non electrically stimulated) lambs from 11 lots killed over 2 days were evaluated. There was a significant difference (P<0.05) between stimulation treatments for initial pH, rate of pH decline and the predicted temperature at pH 6.0. There was also a large difference in the number of carcases that met the recommended window (pH of 6.0, between 18 and 25 degrees C), with an average 67.5% of stimulated carcases and 25% of unstimulated carcases meeting or falling just above the recommended window. The stimulation treatment had no significant (P>0.05) effect on sarcomere length or myofibrillar fragmentation index (MFI) of the m. longissimus (LL). After 1day of ageing LL samples from stimulated carcases had a significantly lower (P<0.05) shear force than non stimulated samples, but there was no difference between stimulation treatments after 5 days ageing. However, ageing period did have a significant effect (P<0.001) on both MFI and shear force, such that 5days aged product had higher MFI and lower shear force values. There were minimal effects of stimulation on colour stability. PMID- 22063031 TI - Ability of near infrared reflectance spectroscopy (NIRS) to estimate physical parameters of adult steers (oxen) and young cattle meat samples. AB - The potential of NIRS-based models to predict several physical parameters of oxen and young cattle beef protected by a quality mark was evaluated. Fifty-three and 67 samples of Longissimus thoracis muscle corresponding to oxen and young cattle reared in extensive conditions were analyzed for pH, colour (L(*), a(*), b(*)), water holding capacity (WHC) and Warner-Braztler shear force (WBSF), according to the conventional methods. Several factors which might have jeopardized the prediction of pH, a(*), WHC and WBSF by NIRS are considered in the discussion section. However, the best NIR calibrations, tested by full cross-validation, were for L(*) (R(2)=0.869; SE(CV)=1.56) and b(*) (R(2)=0.901; SE(CV)=1.08) colour parameters in meat samples from young cattle. It can be concluded that NIRS could be a useful tool for estimating the colour of young cattle meat samples, primary consideration for consumers when making purchasing decisions. PMID- 22063032 TI - Colour, composition and quality of M. longissimus dorsi and M. extensor carpi radialis of steers housed on straw or concrete slats or accommodated outdoors on wood-chips. AB - Forty-five Charolais crossbred steers were offered a common diet and accommodated either outside on wood-chips (OWP, 18m(2)/head) or in a naturally-ventilated building in slatted-floor pens (SLA, 2.5m(2)/500kg bodyweight) or in straw-bedded pens (STR, 4m(2)/head) for 132 days. Carcass weight averaged 351, 362, and 372 (sed 6.63)kg (P<0.05), for SLA, STR and OWP, respectively. Accommodation system did not affect the colour, drip loss, shear force or composition of Musculus longissimus dorsi (LD) or Musculus extensor carpi radialis (ECR) muscles or the sensory characteristics of LD. The ultimate pH of ECR was highest (P<0.05) for OWP steers, while their LD was darker at 2 days post-mortem than LD from STR steers. It is concluded that accommodating cattle on OWP had a minor transient effect on beef colour and no impact on beef composition or eating quality. PMID- 22063033 TI - Contents of creatine, creatinine and carnosine in porcine muscles of different metabolic types. AB - Creatine, creatinine and carnosine have been analyzed by hydrophilic interaction chromatography (HILIC) in seven different pork muscles of different metabolic type (Semimembranosus, Biceps femoris, Gluteus maximus, Longissimus dorsi, Gluteus medius, Trapezius and Masseter). As reported in previous literature, carnosine contents are related with the type of metabolism, being higher in those muscles with glycolytic metabolism. Creatine and creatinine also showed significantly higher concentrations in glycolytic muscles such as Semimembranosus, Biceps femoris, Gluteus maximus and Longissimus dorsi. Masseter, a red oxidative muscle, was characterized by the lowest contents of creatine, creatinine and carnosine and, finally, Gluteus medius and Trapezius, both intermediate muscles, had also intermediate contents of these studied compounds. Finally, a correlation between initial content of creatine and creatinine formation after cooking has been verified using pure standards and two different metabolic type muscles, Longissimus dorsi and Masseter, obtaining slightly higher creatinine amounts in Longissimus dorsi, probably due to its higher initial creatine content and its lower pH. PMID- 22063034 TI - The use of ultrasound to predict the carcass composition of live Akkaraman lambs. AB - The aim of this study was to measure fat thickness, area and depth of the longissimus dorsi muscle using ultrasonography, to estimate carcass composition in live Akkaraman lambs. Fat thickness, area and depth of the longissimus dorsi muscle between the 12th and 13th ribs were measured in vivo and on the carcass after slaughter, using real time ultrasound in 40 Akkaraman lambs. To estimate the carcass composition, one-half of a carcass was dissected into muscle, fat and bone after slaughter. Overall, correlation coefficients between ultrasound and carcass longissimus dorsi muscle area, depth and fat thickness were 0.82, 0.60 and 0.77, respectively. Estimates of carcass composition for Akkaraman lambs based on LW explained 78%, 82%, 74%, 52%, 75%, 36% and 72% of the variations for muscle, total carcass fat, subcutaneous fat, inter-muscular fat, non-carcass fat, tail fat and bone, respectively. The introduction of UFT, ULMA and ULMD as independent variables in addition to LW in the multiple linear regression equations further improved the variations for total muscle (80%), carcass fat (84%) and bone weight (76%) whereas no improvement was observed for subcutaneous, intermuscular, non-carcass and tail fat. The results showed that in vivo ultrasound fat thickness and measurement of area and depth of the longissimus dorsi muscle in association with live weight could be used to estimate muscle, total body fat and bone weight in Akkaraman lambs. PMID- 22063035 TI - Assessment of the oxidative and hydrolytic degradation of the lipid fraction of mortadella by means of HPSEC analyses of polar compounds. AB - The aim of this work was to use the HPSEC analysis of polar compounds to assess the level of oxidative and hydrolytic degradation of the lipid fraction of mortadella. The results indicated high primary oxidative degradation of the lipid fraction in the samples, with a mean value for oxidized triacylglycerols of 1.77%, and low secondary oxidation, with a mean value for triacylglycerol oligopolymers of 0.16%. In addition, in some cases, significant hydrolytic degradation was found. HPSEC analysis of polar compounds, to evaluate the level of oxidative and hydrolytic degradation of the mortadella lipid fraction, could be used as an alternative to commonly used techniques, some of which are not always reliable. PMID- 22063036 TI - Effects of dietary soybean oil on lipid and protein oxidation in pork patties during chill storage. AB - The effect of dietary soybean oil on lipid and protein oxidation in low and high fat pork patties made from quadriceps femoris during chill storage in a high oxygen atmosphere packaging (80% O(2)/20% CO(2)) in the dark for 7 days was investigated. Pigs were fed either a standard diet or a diet added 2% soybean oil. After slaughter high fat pork patties were prepared for both feeding regimes by addition of back fat from pigs fed the same diet whereas low fat pork patties were prepared without addition of back fat. The 2% soybean diet increased the amount of unsaturated fat in the pork. Secondary lipid oxidation products determined as thiobarbituric acid reactive substances (TBARS) were found to increase in the pork patties with increased unsaturated fat. Increased unsaturated fat in the pork patties had no effect on protein oxidation determined as free protein thiol content and protein carbonyl content. A small, but significant increase in protein oxidation was found in the high fat pork patties independent on dietary fat. In conclusion, protein oxidation is unaffected by dietary fat in pork patties during chill storage for periods normally used in retail trade, and lipid and protein oxidation are not coupled under these conditions. PMID- 22063037 TI - Instrumental reflectance values of fresh pork are dependant on aperture size. AB - The effect of aperture size on instrumental pork color measurements was studied. Pork longissimus chops (n=30) were cut, aerobically packaged, and allowed to bloom overnight. Chops were measured once with each of four aperture ports (4.45, 2.54, 1.27, and 0.64cm diameter) on a HunterLab LabScan. Reflectance values measured with smaller aperture sizes were reduced (P<0.05) for most visual wavelengths (10nm intervals), and the percent reduction was greatest in the range of the longer, redder wavelengths. Values for L(*), a(*), b(*), and saturation index were reduced (P<0.05) with decreasing aperture size under illuminants A, C, and D(65). Using illuminant A, hue angle increased (P<0.05) as aperture size decreased. For illuminants C and D(65), hue angles were similar (P>0.05) for the three largest aperture sizes, but negative a(*) values found with the smallest aperture size skewed the hue angle data. PMID- 22063038 TI - Dielectric and thermophysical properties of different beef meat blends over a temperature range of -18 to +10 degrees C. AB - Dielectric and thermophysical properties of three different beef meat blends (lean, fat and 50:50 mixture) were evaluated over a range of temperatures from 18 to +10 degrees C. In the region of thawing (-3 to -1 degrees C), dielectric constant (epsilon') and dielectric loss factor (epsilon') values for radio frequency (RF) and microwave (MW) were significantly higher (P<0.05) than at other measured temperatures for the three blends. In the same region, thermal conductivity (k), specific heat (c) and thermal diffusivity (alpha) also showed significant changes (P<0.05). k and alpha values were significantly lower, while c values were significantly higher in this region than at other measured temperatures for the three blends. RF (27.12MHz) vs. MW (896 and 2450MHz) frequencies had an important effect (P<0.05) on the measured dielectric properties of the beef meat blends, with a general tendency towards higher values at the RF frequency. Finally, composition significantly influenced (P<0.05) the measured dielectric and thermophysical properties at all temperatures used. These data are of potential value to food technologists in the context of rapid defrosting of meat products. PMID- 22063039 TI - Determination of added fat in meat paste using microwave and millimetre wave techniques. AB - By evaluating the sensitivity of measurement parameters such as dielectric constant and microwave loss to fat content, several microwave and millimetre methods were compared to identify optimal frequency measurement bands. The results showed that the optimum frequency range lay between 8 and 20GHz where these parameters vary linearly, by up to a factor of 8, as fat is increased to 50% volume. A narrowband waveguide sensor cell was designed and constructed for this optimum range. The imaginary part (epsilon'') of the complex permittivity demonstrated a better measurements resolution for determining fat content than the real part (epsilon'). The waveguide method has excellent repeatability as indicated by low relative standard deviation (RSD<4.88%). Temperature and sample density had minimal impact on the accuracy, repeatability and robustness of the final measurement system. A method of mixtures model for complex permittivity was shown to be a useful predictor of fat content. PMID- 22063040 TI - The effect of mutations in the insulin-like growth factor-II and ryanodine receptor-1 genes on biochemical and histochemical muscle fibre characteristics in pigs. AB - Mutations in IGF-II (insulin-like growth factor-II) and RYR1 (ryanodine receptor 1) increase lean meat content in pigs but with different effects on meat quality. Differences in biochemical and histochemical muscle fibre characteristics between the two mutations can thus be suspected. Therefore, the aim of this study was to investigate the effect of the IGF-II mutation (Apat vs. Gpat) on biochemical and histochemical muscle fibre characteristics in relation to the RYR1 genotype (Nn vs. NN). A prenatal effect of the IGF-II mutation could not be excluded but the increased leanness in both mutations was clearly related to postnatal muscle hypertrophy due to an increase in muscle fibre diameter and a higher proliferative capacity in animals carrying the IGF-II mutation. No effect of the IGF-II or RYR1 mutation was found on fibre type composition and metabolic enzyme activities. Interactions between IGF-II and RYR1 genotypes suggest that the mechanism involved in increased leanness due to the impaired RYR1 receptor might influence the underlying mechanisms of the IGF-II mutation. PMID- 22063041 TI - Influence of different types and proportions of added edible seaweeds on characteristics of low-salt gel/emulsion meat systems. AB - The effects of three different types of edible seaweeds, Sea Spaghetti (Himanthalia elongata), Wakame (Undaria pinnatifida), and Nori (Porphyra umbilicalis) added at two concentrations (2.5% and 5% dry matter) on the physicochemical and morphological characteristics of gel/emulsion systems were evaluated. The addition of seaweeds improved (P<0.05) water- and fat-binding properties except in the case of Nori added at 2.5%. Hardness and chewiness of the cooked products with added seaweed were higher (P<0.05), and springiness and cohesiveness were lower (P<0.05) than in control samples. Colour changes in meat systems were affected by the type of seaweed. The morphology of sample differed depending on the type of seaweed added, and this is the result of differences in physical and chemical characteristic of the seaweed powder used. In general, products formulated with the brown seaweeds (Sea Spaghetti and Wakame) exhibited similar behaviour, different from that of products made with the red seaweed Nori. PMID- 22063042 TI - Effect of animal (lamb) diet and meat storage on myofibrillar protein oxidation and in vitro digestibility. AB - Effect of pasture- or concentrate-diet on myofibrillar protein oxidation and in vitro digestibility was measured in lamb meat (M. longissimus dorsi) during a refrigerated storage of 7days under gas permeable film. Protein oxidation was measured by the carbonyl content determined chemically using 2,4 dinitrophenylhydrazine (DNPH) and specific targets of oxidation were identified by immunoblotting. Carbonyl content significantly increased during storage and diet affected protein oxidation where animals fed concentrate showed higher carbonyl group levels than animals fed pasture. To evaluate effect of diet and storage time on protein digestibility, myofibrillar proteins were exposed to proteases of the digestive tract (pepsin, and a mixture of trypsin and alpha chymotrypsin) in conditions of pH and temperature which mimic digestive process. The myofibrillar protein digestibility was not influenced by the diet. Storage time had no significant effect on myofibrillar protein susceptibility to pepsin while an important increase in digestibility by trypsin and alpha-chymotrypsin was detected during storage. PMID- 22063043 TI - Proteolysis in Painho de Portalegre dry fermented sausage in relation to ripening time and salt content. AB - The effect of salt addition (3% and 6% in the final product) on the shelf-life related physicochemical characteristics and proteolysis profile during the ripening period of a Portuguese dry fermented sausage "Painho de Portalegre", were evaluated. The product with 6% salt concentration had low a(w) and pH values at most ripening periods evaluated, due to the influence of NaCl on the water binding capacity of the protein structure and to the low ammonia accumulation, respectively. Similar changes were observed for total basic volatile nitrogen (TBVN), free amino acid nitrogen (FAAN) and non-protein nitrogen (NPN) fractions in both products. After a clear increase during the first days of the processing phase, all the initial rates slowed down with some fluctuation in FAAN and NPN. In relation to small peptides and free amino acid accumulation, the major differences between the tested formulations were mainly observed on distinct profiles rather than on overall concentrations. PMID- 22063044 TI - Explaining and predicting differences in meat quality through stress reactions at slaughter: The case of Large White and Duroc pigs. AB - Large White and Duroc pigs (n=42) were group-reared on straw. Durocs were more active in the home pens and had higher basal urinary cortisol levels. During tests, Durocs touched more often an unfamiliar human, but not an unfamiliar object, than Large Whites. Pigs were experimentally (low stress) or industrially (high stress) slaughtered. Meat (Longissimus lumborum (LL), Biceps femoris (BF), Adductor femoris (AF) and Semimembranosus (SM)) was darker, more yellow, had higher ultimate pH and better water holding capacity after high, compared to low stress slaughter. Large White meat contained less pre-slaughter glycogen, was redder and lost more drip. Slaughter conditions influenced ultimate pH of Large White more than of Duroc meat. Large Whites, and to a lesser extent Durocs, touching the human less often during the test, had faster early post-mortem LL and BF muscle metabolism. Pigs exploring the unfamiliar object more often were more aggressive during pre-slaughter mixing and had higher AF and SM ultimate pH. PMID- 22063045 TI - The significance of diet, slaughter weight and aging time on pork colour and colour stability. AB - The objective of the present study was to investigate the effect of a diet with a low content of digestible starch, slaughter weight and subsequent aging time on meat colour and colour stability. Pork colour was determined as the extent of blooming of M. longissimus thoracis (LT) and M. semimembranosus (SM) after 1, 2, 4, 8 and 15 days postmortem and as colour stability during a subsequent storage period in air for 6 days. Compared to the control diet, the experimental diet resulted in a significantly lower postmortem muscle temperature (1 degrees C; p<0.0001). Moreover, high slaughter weight (110kg) resulted in a higher postmortem temperature in LT (p<0.001) compared to low weight (85kg). Independent of feeding strategy and slaughter weight, the extent of blooming decreased during the first 2-4 days of aging in LT, however, the effect was more pronounced in meat from experimentally fed pigs and pigs with high slaughter weight. This effect was not seen in SM, where a gradual increase in blooming took place throughout the aging period. The colour stability was found to be superior in aged pork from experimentally fed pigs. The discoloration rate was faster in SM compared to LT. In conclusion, the present study shows that the diet composition can be used as a tool to control meat colour and colour stability in pork. PMID- 22063046 TI - Microbial heat resistance of Listeria monocytogenes and the impact on ready-to eat meat quality after post-package pasteurization. AB - Several methods using bactericides, hydrostatic pressure, and post-package pasteurization technologies to control Listeria monocytogenes (LM) in ready-to eat meats have been attempted. In addition to controlling LM contamination, any newly developed technology must have minimal effects on organoleptic properties. The objectives of this study were to: (1) determine the heat resistance of LM in two brands (A and B) of bologna differing in formulations, and, (2) evaluate the effects of post-package pasteurization on product quality. Fat content did not affect LM heat resistance in bologna at 55, 60, and 65 degrees C; however, Brand B bologna had a numerically lower inactivation rate. Microbial heat resistance differed (P<0.05) with changes in pasteurization temperature. Time and temperature affected (P<0.05) cook-loss and L(*) Hunter color value for both bologna brands. These data show that post-package pasteurization is effective but suggest that meat formulations may need modification to prevent development of negative quality characteristics. PMID- 22063047 TI - Eating quality of beef, from different production systems, assessed by German, Spanish and British consumers. AB - The acceptability of beef from Uruguay (UY), based on eating quality, was compared with beef produced in different European countries (Germany, DE, Spain, ES and United Kingdom, UK). Consumer tests were conducted in DE, ES and UK (each comprising 200 consumers) using 'Hall Tests'. In each country four samples were evaluated, two from Hereford steers from UY (finished at 2 and 3 years) and two from local meat (the same meat sample aged 7 or 20d). Consumers evaluated tenderness, flavour and overall acceptability using 8-point category scales. Hierarchical cluster analysis, highlighted the existence of different clusters of consumers. Two main clusters were identified in DE and UK. The main cluster identified in DE, was labelled as Prefer foreign-imported beef (n=128). These consumers preferred (P<0.05) the samples from UY_2y in terms of tenderness and overall acceptability. The other cluster was labelled as Prefer local beef in terms of flavour and overall acceptability (P<0.05) and comprised the majority of consumers from ES (n=176) and UK (n=153) and the cluster 2 from DE (n=69). UK, cluster 2 (n=33) that did not discriminate between origin and ageing time of beef. These results indicate that consumers did not prefer the same type of meat within the same country and it is possible that there are individual preferences that could lead to the concept of market segmentation being based on taste preferences. It would appear that Uruguayan beef would be very acceptable in Germany and to a lesser extent in Britain and Spain, although further studies are required that include labelling information. PMID- 22063048 TI - Changes in the forms of iron and in concentrations of taurine, carnosine, coenzyme Q(10), and creatine in beef longissimus muscle with cooking and simulated stomach and duodenal digestion. AB - Longissimus muscle samples from 31 Angus-cross heifers finished on either a high concentrate feedlot diet or pasture were used to evaluate the effects of cooking (71 degrees C) on the concentration and forms of iron in the meat, and also on concentrations of the bioactive compounds taurine, carnosine, coenzyme Q(10), creatine and creatinine. For a sub-sample of 15 the effects of pepsin and pancreatin digestion were assessed. For iron, cooking resulted in some overall loss together with a major change from soluble haem and non-haem iron to the insoluble forms, but solubility was regained to a significant extent following digestion. Total haem iron percentage, however, decreased at each step from an initial 88% to a final 61% of total iron. For the bioactive compounds, cooking led to a reduction in taurine, carnosine, coenzyme Q(10), and creatine. The effects of digestion on the bioactive compounds varied. No clear differences were shown in the way in which beef from pasture-finished and feedlot-finished cattle responded to cooking and digestion. PMID- 22063049 TI - Changes of arginyl and leucyl aminopeptidase activities in biceps femoris along Jinhua ham processing. AB - Sixty experimental Jinhua hams were processed by a traditional method. The potential arginyl (RAP) and leucyl (LAP) aminopeptidase activities in biceps femoris were determined. The effects of temperature, salt content, sodium nitrate content and pH value on muscle RAP and LAP activities were evaluated using response surface methodology. Porcine muscle was found to possess very strong potential RAP and LAP activities that decreased gradually during processing from 165,980.97Ug(-1) and 89,201.52Ug(-1) before salting to 3164.70Ug(-1) and 5373.66Ug(-1) after aging, respectively. Temperature, pH value and salt content had significant effects on RAP and LAP activities (P<0.0001). They interacted with each other in their effects on RAP activity (P<0.0001) and influenced LAP activity in exponential way (P<0.05). However, 0-50mgL(-1) sodium nitrate had no detectable effect on either RAP or LAP activity (P>0.05). The regression models showed that muscle RAP and LAP maintained their activities all through Jinhua ham processing. LAP could display very strong actual activity during aging and post aging, indicating that muscle LAP may play the most important role in generating free amino acids during the processing of Jinhua ham. PMID- 22063050 TI - Effects of transport time and rest period on the quality of electrically stimulated male cattle carcasses. AB - Forty-five castrated Nelore-breed male cattle, with average age of 37 months, were randomly chosen. The cattle were submitted to the combination of two transport times (up to 2h and approximately 5h) and five rest periods (0h, 6h, 12h, 18h and 24h). The carcasses were electrically stimulated. After 24h postmortem, the average of the ultimate pH in the M. Longissimus dorsi (LD) was considered normal (5.57-5.72) for eight out of nine cattle groups. The shear force (SF) was higher for cattle that were not allowed a rest period (0h) on both transport times, however it was not significant (p>0.05). This result was compatible with the sarcomere length (SL), which were shorter for those carcasses. The rest period and transport time had no influence on the L(*) (lightness) values, but a(*) (redness) values increased until the 12th hour of rest. The b(*) (yellowness) value was negative for the cattle without a rest period (0h) and transported for 5h. The cattle transported for up to 2h could be allowed a 6-h rest period only, and the cattle transported for 5h could be allowed a 12-h rest period without the meat quality being affected significantly. PMID- 22063051 TI - The effect of sugar concentration and starter culture on instrumental and sensory textural properties of chorizo-Spanish dry-cured sausage. AB - In this study, instrumental and sensory textural properties of chorizo with different levels of glucose (0.1%, 0.5% and 1.0%) and with different starter cultures (Lactobacillus sakei K29, Pediococcus sp. P22 and Pediococcus sp. P208) were studied as well as the relationship between them. The ripening process was followed by physico-chemical and microbiological analysis. Starter culture and concentration of glucose had a highly significant effect on pH, moreover an interactive effect of both factors was found; and also of day of ripening and both starter culture and concentration of glucose. In general terms, changes of pH over time are influenced by the presence of sugar and starter culture even if all chorizos showed at first a rapid decrease, a stay or slow decrease, and a final rise. Texture profile analysis (TPA) proved that hardness and chewiness differ significantly among chorizos with or without starter cultures, except in the batch with 0.1% sugar. Furthermore, the highest values in both textural parameters were found in batches with 0.5% and 1% sugar. The texture differences between chorizos just described were also noticeable in the sensorial evaluation. Likewise, instrumental textural attributes showed significant correlations with sensorial analysis. PMID- 22063052 TI - Effect of dietary antioxidant and fatty acid supply on the oxidative stability of fresh and cooked pork. AB - The effect of dietary oil (linseed or soybean oil) and antioxidant treatment (alpha-tocopheryl acetate (AT; 40ppm) versus a cocktail (AOC; 200ppm): alpha tocopheryl acetate+rosemary+citric acid+gallic acid) on colour, lipid and protein oxidation of fresh and processed pork was investigated. No effect of oil source on different parameters of oxidation was seen. No effect of antioxidant treatment on colour stability of fresh longissimus thoracis (LT) or cooked cured ham (CCH) was observed. For both antioxidant treatments, lipid oxidation in fresh LT and CCH was well controlled during display. However, lipid oxidation increased significantly in pre-frozen uncured cooked meat under aerobic conditions. No unambiguous effect of antioxidant treatment on protein oxidation was observed. There seemed to be no clear link between colour, protein and lipid oxidation. At the dose used in this study, no additional or synergistic effects of the extra components of the AOC on the different oxidation parameters was found. PMID- 22063053 TI - Potential use of near infrared reflectance spectroscopy (NIRS) for the estimation of chemical composition of oxen meat samples. AB - Near infrared reflectance spectroscopy (NIRS) was evaluated as a tool to estimate several chemical parameters of oxen meat protected by a quality mark. Fifty-three samples of longissimus thoracis muscle corresponding to oxen reared in extensive conditions were homogenized and scanned over the NIR spectral range (1100 2500nm). Immediately after scanning, the samples were analyzed for crude protein (CP), myoglobin, collagen, ether extract (EE), gross energy (GE), dry matter (DM) and ash content, according to the official methods. Best NIR calibrations for chemical composition tested by cross-validation showed R(2) and SE(CV) of 0.874 and 20.33gkg(-1) DM (CP), 0.924 and 16.22gkg(-1) DM (EE), 0.941 and 0.293MJkg(-1) DM (GE) and 0.874 and 6.75gkg(-1) FM (DM). Calibrations for myoglobin, collagen and ash content showed a poor predictability, probably as a consequence of the lack of correlation between these parameters and EE content. However, NIRS technology could be an useful tool for estimating the main chemical parameters of oxen meat samples, thus guaranteeing the standards of quality marks. PMID- 22063054 TI - Validation of the EUROP system for lamb classification in Norway; repeatability and accuracy of visual assessment and prediction of lamb carcass composition. AB - The EUROP classification system is based on visual assessment of carcass conformation and fatness. The first objective was to test the EUROP classification repeatability and accuracy of the national senior assessors of the system in Norway. The second objective was to test the accuracy of the trained and certified abattoir EUROP classifiers in Norway relative to EU Commission's supervising assessors. The third and final objective was to test the accuracy of the EUROP classification system, as assessed by the National senior assessors, for prediction of lean meat, fat and bone percentage and lean meat in relation to bone ratio. The results showed that the repeatability and accuracy of the national senior assessors was good, achieving high correlations both for conformation and fatness. For the abattoir assessors, there were some systematic differences compared to EU Commission's assessors, but these differences were within limits accepted by EU Commission. The relationship between abattoir and national senior assessors was good, with only small systematic differences. This may suggest that there also is a systematic difference between the national senior assessors of the system and EU Commission's assessors. The EUROP system predicted lean meat percentage poorly (R(2)=0.407), with a prediction error for 3.027% lean. For fat and bone percentage, the results showed a fairly good prediction of fat percentage, but poorer for bone percentage, R(2)=0.796 and R(2)=0.450, respectively. The prediction error for fat and bone percentage was 2.300% and 2.125%, respectively. Lean: bone ratio was predicted poorly (R(2)=0.212), with a prediction error of 0.363 lean: bone ratio. PMID- 22063055 TI - The effects of freeze-thaw and sonication on mitochondrial oxygen consumption, electron transport chain-linked metmyoglobin reduction, lipid oxidation, and oxymyoglobin oxidation. AB - Mitochondria potentially influence Mb redox stability in meat by (1) decreasing partial oxygen pressure via oxygen consumption, (2) mitochondrial electron transport chain (ETC)-linked reduction of MetMb, and/or (3) oxidation of mitochondrial membrane lipid. The objective of this study was to investigate the effect of freeze-thaw and sonication treatments on mitochondrial oxygen consumption, ETC-dependent MetMb reducing activity, lipid oxidation, and Mb redox stability. Mitochondria were frozen and thawed (-18 degrees C for 2h and 4 degrees C for 0.5h) for 3 cycles, or sonicated for 30s with a sonic dismembrator. State III oxygen consumption rate (OCR) was decreased by both treatments at pH 7.2, and by sonication only at pH 5.6 (P<0.05). There was no effect on state IV OCR (P>0.05). Respiratory control ratio (RCR) was decreased by freeze-thaw and sonication at pH 7.2 and 5.6 (P<0.05). Sonication increased mitochondrial lipid oxidation and MetMb formation (P<0.05); a similar effect was observed in sonicated samples in the presence of ascorbic acid and ferric chloride (P<0.05). Sonication also decreased mitochondrial ETC-dependent MetMb reduction (P<0.05). These results suggested that sonication treatment had the potential to affect Mb stability via mitochondrial lipid oxidation and/or ETC-mediated MetMb reduction, but the effect on myoglobin stability by freeze-thaw treatment was minimal. PMID- 22063056 TI - The relationship of physiological maturity and marbling judged according to Korean grading system to meat quality traits of Hanwoo beef females. AB - Fifty seven carcasses from Hanwoo beef females were randomly selected by official meat graders and were sorted into three levels of maturity and marbling. Carcass data was collected for back fat thickness, longissimus area, carcass weight, meat colour, fat colour, marbling score, yield and quality grades. Mature carcasses had more yellow fat, coarser texture, a larger longissimus muscle area and lower quality grades and marbling scores (P<0.05). Carcasses with a higher marbling score had thicker fat and a higher quality grade. Carcasses with low marbling had a higher yield grade and a coarser texture (P<0.05). Higher marbling scores corresponded with lower cook and drip loss values for longissimus steaks. As the maturity of carcass was increased, the redness and lightness of meat and the yellowness of fat all tended to increase. Tenderness, flavour and overall acceptability scores for the older maturity group were lower than for younger and intermediate groups. Marbling was significantly (P<0.01) correlated with quality grade, crude fat content, cook and drip losses, and Warner-Bratzler shear force. The maturity level was also significantly (P<0.01) correlated with quality grade, fat colour, texture score, number of calves produced and milk teeth, meat redness and yellowness, fat yellowness, and Warner-Bratzler shear force. Results indicate that a low marbling group and older maturity group based on Korean grading system could negatively influence carcass traits and beef qualities of Hanwoo beef female. PMID- 22063057 TI - Comparison of composition and quality traits of meat from young finishing bulls from Belgian Blue, Limousin and Aberdeen Angus breeds. AB - Thirty-six young finishing bulls from three breeds (Belgian Blue, Limousin and Aberdeen Angus) were fattened over five months with finishing diets based either on sugar-beet pulp or on cereals. Nutritional quality traits of meat - fat content and fatty acid composition with emphasis on the n-6 and n-3 polyunsaturated fatty acids - along with some organoleptic quality traits were measured. The Belgian Blue bulls had the lowest intramuscular fat content associated with lower saturated and monounsaturated fatty acid contents. The polyunsaturated fatty acid content did not differ to a large extent between the breeds, the Aberdeen Angus bulls showing slightly higher values. Relative to energy intake, the overall contribution of meat to the n-3 fatty acid recommended intake was small, whatever the breed. By contrast, the contribution of meat to daily fat intake was of greater importance, especially for the Aberdeen Angus bulls. The quality traits of meat varied also according to the breed: compared to the Aberdeen Angus, the Belgian Blue bull meat had the stablest colour, the highest drip and the lowest cooking losses. The meat of Limousin bulls had intermediate characteristics for all the parameters. PMID- 22063058 TI - The sensory acceptability of cooked meat products treated with a protective culture depends on glucose content and buffering capacity: A case study with Lactobacillus sakei 10A. AB - Biopreservation has been proven to be a promising natural preservation technique, but the impact of protective cultures on the sensory properties of cooked meat products (CMP) is not well documented. This work presents a case study on the protective culture Lactobacillus sakei 10A to obtain a clear view on the real consequences of using protective cultures on the sensory quality of CMP. A preliminary screening study on 13 different CMP and more elaborate application trials at 7 degrees C on vacuum packaged pate, cooked ham, cooked sausage and two cooked poultry products demonstrated that L. sakei 10A inhibits the endogenous LAB-flora, Leuconostoc mesenteroides, Brochothrix thermosphacta and Listeria monocytogenes. Despite these promising antagonistic effects, the application of L. sakei 10A to CMP was in some cases limited by a significant acidification resulting in an acid taste of the product. This was most obvious in pate and cooked sausage and less obvious in cooked turkey fillet. From the results a hypothesis could be derived that high buffering capacity and low glucose content are key elements to avoid sensory deviations when applying protective cultures on CMP. PMID- 22063059 TI - Influence of animal temperament and stress responsiveness on the carcass quality and beef tenderness of feedlot cattle. AB - Three groups of steers (A, B, C) were used to study the effect of temperament (Calm, Intermediate, and Excitable) on meat quality. Temperament was based on exit velocity, pen scores, and chute scores. Temperament traits were consistent across evaluations, and values decreased (P<0.05) in magnitude over time. Increasing excitability was associated with higher (P<0.05) serum cortisol concentrations. Carcasses from cattle with calm temperaments had higher (P<0.05) 0.5h postmortem pH values than those from Intermediate and Excitable cattle (0.1 and 0.2 units, respectively). Group C Excitable steers had higher (P<0.05) WBS values than the calmer Group C steers. This trend was observed in Group A steers, although the values were not statistically different. Correlations were highest between temperament values and tenderness after 21d. Temperament influences tenderness, although the mechanism is not clear. PMID- 22063060 TI - Prevalence of biogenic amines during ripening of a traditional dry fermented pork sausage and its relation to the amount of sodium chloride added. AB - The presence of biogenic amines (BA) along the processing stages and storage period of "Painho de Portalegre" and its relationship with the NaCl concentration on their levels were evaluated. Total BA concentration of current "Painho de Portalegre" dry fermented sausage increased (P<0.001) with drying/smoking processing time, attaining 655mgkg(-1) dry matter (DM) at day 6, a level about six times higher than that obtained in seasoned raw material mixtures before casing stuffing (115mgkg(-1)DM). Between day 30 and 40 in the drying/smoking house, that amount increased 20-fold (2500mgkg(-1) DM) over the initial concentration. After one month of storage under vacuum at room temperature, the concentration decreased by almost half to 1561mgkg(-1)DM. Excluding tyramine, the other BA were already present in the minced raw materials. However the sum of cadaverine, putrescine, histamine and tyramine, was well below 5mgkg(-1) proposed as BA limit for meat of high hygienic quality. Cadaverine was the most concentrated BA at the last stage of the drying/smoking (1430-1254mgkg(-1)DM, after 30 and 40 days, respectively), almost double the concentration of putrescine (882-779mgkg(-1)DM), followed by tyramine, beta-phenylethylamine and spermine (376-311, 24 and 27-23mgkg(-1)DM, respectively). Variation was detected among production batches, possibly due to poor control of the processing conditions in traditional manufactures and the effects of the prevailing weather conditions. A higher salt concentration in the final product, 6% compared to 3%, led to a significant reduction in the BA level (P<0.001). This difference was particularly relevant in the early stage of the drying/smoking phase, during which the greatest microbial development mainly occurred in relation to cadaverine, beta-phenylethylamine, putrescine and tyramine levels. PMID- 22063061 TI - Application of an electronic nose for measurements of boar taint in entire male pigs. AB - An electronic nose based on ion mobility spectrometry was used for boar taint measurements of entire male pig samples varying in androstenone and skatole levels (0.09-0.88MUg/g fat and 0.01-0.26MUg/g fat, respectively). Sensory perceptible boar taint (especially boar odour) was found to be more related to androstenone than to skatole, whereas a rancid note was determined more related to skatole than to androstenone. Multivariate models implementing some generally prescribed cut-off limits for androstenone (0.50MUg/g) and skatole (0.21MUg/g) indicated that the e-nose could be used for ordering samples with respect to low and high levels of androstenone and skatole. Studying the direct relationships between e-nose data, sensory data, androstenone and skatole showed better predictivity of the chemical compounds (androstenone: r=-0.948, RMSEP=0.309; skatole: r=-0.629, RMSEP=0.069) than for single sensory descriptors (boar odour r=0.409, RMSEP=0.789). The results thus suggest that the e-nose technology based on ion mobility spectrometry as in the MGD-1 may have a potential for future rapid sorting of boars at the slaughter line. The study provides new knowledge of the applicability of ion mobility spectrometry for measuring boar taint and also confirms the challenge of measuring boar taint using chemically determined cut off limits for a sensory perceptible phenomenon. Thus, future development should be more devoted to developing holistic approaches rather than focusing on the influence of single variables on boar taint. PMID- 22063062 TI - Contribution of postmortem changes of integrin, desmin and MU-calpain to variation in water holding capacity of pork. AB - The purpose of this study was to examine the relationship between integrin, desmin, MU-calpain and water holding capacity in fresh pork. High levels of intact integrin at one day postmortem were negatively correlated with day 1 (P<0.05) and days 1-5 (cumulative) drip loss (P<0.05). High levels of intact integrin at five days postmortem were negatively correlated with days 1-7 (cumulative) purge loss (P<0.05). Intensity of intact desmin at one day postmortem was positively correlated with days 1-7 purge loss (P<0.01). There were positive correlations between intensity of intact desmin at day 7 and day 1 (P<0.01), days 1-5 drip loss (P<0.01) and days 1-7 purge loss (P<0.05). Autolysis of MU-calpain was associated with the degradation of desmin and drip or purge loss postmortem. Our results indicate that low levels of degradation of integrin and high levels of desmin degradation were associated with low drip loss values in fresh pork. PMID- 22063063 TI - Changes in proteins during Teruel dry-cured ham processing. AB - The aim of this work was to investigate the degradation of the water-soluble and myofibrillar proteins during the production of "PDO Teruel" cured ham using SDS PAGE, and measurement of proteolytic activities (cathepsins B+L, cathepsin L, cathepsin D), as factors that influence the sensory characteristics of this product. This paper contributes to the specific characterisation of a product included in the European Union list of special quality products. The results showed that water-soluble proteins decrease considerably due to salting out and drainage after salting. The degradation of myofibrillar proteins is more pronounced during the ripening process, particularly in the last four months when the main proteins responsible for the structure of muscular tissue are affected. There is an important residual enzymatic activity for cathepsin B, L and D, which must be a decisive factor in the proteolysis observed during "PDO Teruel" ham processing. PMID- 22063064 TI - Observation of the distribution of Zn protoporphyrin IX (ZPP) in Parma ham by using purple LED and image analysis. AB - We investigated the distribution of Zn protoporphyrin IX (ZPP) in Parma ham by using purple LED light and image analysis in order to elucidate the mechanism of ZPP formation. Autofluorescence spectra of Parma ham revealed that ZPP was present in both lean meat and fat, while red emission other than that of ZPP was hardly detected. Although ZPP was found to be distributed widely in Parma ham, it was more abundant in intermuscular fat and subcutaneous fat than in lean meat. The intensity of red emission was weak in muscles that were exposed during the processing. ZPP in both lean meat and subcutaneous fat tended to be more abundant in the inner region than in the outer region. It was thought that ZPP is transferred from lean meat to fat tissue during the processing, resulting in the small amount of ZPP in the lean meat adjacent to subcutaneous fat. Our results led to a completely new hypothesis that ZPP is formed in lean meat and transferred to fat tissue. PMID- 22063065 TI - Plasma leptin in growing lambs as a potential predictor for carcass composition and daily gain. AB - Leptin is an adipocyte derived hormone and correlates highly to the extent of body fat tissue. The aim of this study was to determine if leptin could serve as an early predictor for carcass composition and final growth rate in lambs with special emphasis on size and cellularity of the different body fat depots. Thirty intact male ad libitum fed lambs were blood sampled at 20, 25, 30, 35, and 40kg live weight. After slaughtering at 40kg, lean and the visceral, subcutaneous and intermuscular fat were measured by dissection. The fat cell diameter was determined in subcutaneous and perirenal fat. Average daily gain from birth to slaughter correlated to leptin only at 30 and 35kg live weight (r=-0.56 and 0.61, P<0.01) and thus leptin cannot be regarded as a suitable early predictor for growth rate. That goes for the prediction of subcutaneous and intermuscular fat, too; because no relationships were detected between early leptin concentrations and the amount of these tissues. Leptin concentrations measured just before slaughter were related to all fat tissues except the pelvic and intramuscular fat. Among the visceral fat depots, omental fat expressed the highest correlations to leptin (r=0.60, P<0.001). Additionally, leptin concentrations at 35 and 40kg live weight increased with increasing fat cell diameters (r=0.38, P<0.05 to r=0.59, P<0.001). This study indicates that leptin concentration measured in the slaughter weight range has the greatest potential to assess body fat content, whereas an earlier prediction does not seem to be feasible. Further studies should clarify if these results are reproducible for other breeds or species. PMID- 22063066 TI - Role of the blood service in cellular therapy. AB - Cellular therapy is a novel form of medical or surgical treatment using cells in place of or in addition to traditional chemical drugs. The preparation of cellular products - called advanced therapy medicinal products - ATMP in Europe, requires compliance with good manufacturing practices (GMP). Based on long-term experience in blood component manufacturing, product traceability and hemovigilance, selected blood services may represent ideal settings for the development and experimental use of ATMP. International harmonization of the protocols and procedures for the preparation of ATMP is of paramount importance to facilitate the development of multicenter clinical trials with adequate sample size, which are urgently needed to determine the clinical efficacy of ATMP. This article describes European regulations on cellular therapy and summarizes the activities of the 'Franco Calori' Cell Factory, a GMP unit belonging to the department of regenerative medicine of a large public university hospital, which acquired a certification for the GMP production of ATMP in 2007 and developed nine experimental clinical protocols during 2003-2011. PMID- 22063067 TI - The kinetics of cooked meat haemoprotein formation in meat and model systems. AB - The rate of cooked meat haemoprotein formation (measured as the rate of loss of myoglobin solubility) was found, at least initially, to obey first order kinetics in meat, aqueous muscle extracts and mixtures of myoglobin and bovine serum albumin. In meat at 60 degrees C the rate was dependent on the species, (the pigment was formed significantly faster in lamb m. longissimus dorsi than in beef m. longissimus dorsi) and anatomical location (cooked meat haemoprotein was formed in beef m. 1. dorsi about twice as rapidly as in both beef shin and chuck (shoulder) muscle of similar pH). The rate of formation was similar in aqueous muscle extracts to that found in meat and in these systems increased with decreasing pH. The activation energies for all beef systems studied were similar and typical of those associated with protein denaturation (~300 KJ mol(-1)); however, that from lamb appeared to be lower (~200 KJ mol(-1)). The problems of using colour as an index of temperature reached, either for microbial safety (E. Coli 0157:H7 destruction) or quality are discussed in the light of these results. PMID- 22063068 TI - Degradation of ubiquitin in beef during storage. AB - Sarcoplasmic proteins were prepared from the quadriceps femoris muscle immediately after slaughter (2.5 hr) and from stored muscle samples at 10 days post mortem for SDS-PAGE analysis and Western blotting. Characterization with ubiquitin antiserum (Sigma, St. Louis, MO, USA) showed clear and strong recognition of ubiquitin (8.6 kDa) and another minor band (17 kDa) in purified ubiquitin (Sigma, St. Louis, MO, USA). Among the sarcoplasmic proteins prepared, this antiserum also reacted with the bands corresponding to purified ubiquitin (8.6 kDa and 17 kDa) and a small amount of some other higher-molecularmass proteins which were considered to be ubiquitin-protein conjugates. However, at 10 days post mortem, both ubiquitin and the ubiquitin-protein conjugates had almost disappeared, suggesting their degradation by proteinases. PMID- 22063069 TI - Ostrich meat: Physico-chemical characteristics and comparison with turkey and bovine meat. AB - In several European countries ostrich breeding has now become quite common. In Italy this has also given rise to the need for regulations for the slaughtering of Ratites. The present work studies and compares the physico-chemical characteristics of the meat from the thigh of the ostrich with the same anatomical cuts of turkey and bovine. The ostrich meat muscle of the thigh was imported vacuum packed from Israel and France, the muscles considered were m. flexor cruris and m. iliofibularis. The turkey thighs were from the domestic market (supermarket) and the bovine muscle m. pectineus was from spent milking animals from an EEC slaughterhouse. Needless to say that the breeding, the feeding and the system of slaughtering could influence some parameters of the different kinds of meat; however these factors could not be assessed. Due to its tenderness, low fat content and cholesterol levels ostrich meat is, in accordance with modern-day nutritional principles, a valid alternative to other kinds of meat. PMID- 22063070 TI - Development of a quality classification system for lamb carcasses. AB - A total of 1660 commercial lambs, with slaughter weights >= 32kg and having no more than two permanent incisors, were selected on the basis of age, weight, gender, and fatness to be representative of the Canadian market lamb population and utilized to develop a quality classification system for lamb carcasses. Based upon the findings obtained, lamb should be defined as carcasses from ovines weighing 32 kg live or more and with no more than two permanent incisors. Mutton should be defined as carcasses from ovines with more than two permanent incisors or carcasses from ovines that have lost their third temporary incisor. Milk-fed lamb should be defined as carcasses from ovines weighing less than 32kg live. Consequently, classification recommendations arising from the present study apply only to carcasses from ovines defined as lamb, according to the previous definitions. Thus, lamb carcasses so defined can be effectively segregated into three quality groups based upon expected consumer acceptance, utilizing simple, subjective evaluations of the breakjoints and ribs, as follows: Group 1 possessing very red and moist breakjoints and round, red ribs, Group 2 possessing slightly red to red breakjoints and oval shaped ribs, which are either slightly red or have traces of red colour, and Group 3 possessing white, dry breakjoints and flat, white ribs. Classification of lamb carcasses on this basis will allow compensation to producers based upon carcass merit, reflecting consumer acceptance. Although availability and consumer demand will ultimately determine price premiums and/or discounts, based upon present findings, Group 1 should contain 9% or less of the lamb carcasses being marketed and should receive a premium to compensate for a higher degree of consumer acceptance. Group 2 should contain 75% or more of the lamb carcasses being marketed and should receive prevailing market value. Group 3 should contain 15% or less of the lamb carcasses being marketed and should receive a discount to compensate for a lower degree of consumer acceptance. PMID- 22063071 TI - Fatty acid and aldehyde composition of individual phospholipid classes of rabbit skeletal muscles is related to the metabolic type of the fibre. AB - The fatty acid composition of individual phospholipid classes as related to metabolic type of fibre in the rabbit was studied. The fatty acid composition of the individual phospholipid classes of five muscles were compared: two glycolytic ones (Longissimus lumborum and Psoas major), two oxidative ones (Soleus and Semimembranosus propriosus,) and an intermediate one (Gastrocnemius laterale). It was shown that except for phosphatidyl inositol (PI), the fatty acid compositions of the main phospholipid classes were strongly related to the metabolic type of the fibres; phosphatidyl ethanolamine (PE) of oxidative muscles contains less 18:2 n-6 and more 18:0 and long chain PUFA of the n-6 and n-3 series than that of glycolytic ones; phosphatidyl choline (PC) of oxidative muscles contains more 18:0 and less 16:0 and 18:2 n-6 than that of glycolytic ones; cardiolipin of the oxidative muscles contains less 18:2 n-6 than those of the glycolytic ones. These differences in fatty acid composition of PE, PC and cardiolipin explain a large part of the differences in fatty acid compositions of the total phospholipids of glycolytic and oxidative muscles. PMID- 22063072 TI - Effect of different stocking densities during transport on welfare and meat quality in Danish slaughter pigs. AB - Four stocking densities (0.35, 0.39, 0.42 and 0.50 m(2) per 100 kg pig) were investigated under Danish early Autumn conditions (16-24 degrees C) in a study of the effect of transport conditions on pig welfare and meat quality. Two transports were carried out for each stocking density, the two producers concerned delivering pigs to the upper and lower tiers, respectively, of a specialist pig transport vehicle. Total average journey time was 2 hr 39 min and total average transport time 1 hr 47 min. After arrival at the factory pigs were lairaged in groups of 15 for about 1 1 2 hr and then slaughtered using minimal stress with group CO(2)-stunning. Pig behaviour was monitored during transport in the front compartment of the lower tier. Blood samples were taken at slaughter for analysis of creatine phosphokinase, lactate and cortisol and carcasses were evaluated for skin damage and meat quality. Stocking density, as such, had relatively little effect on blood profile or meat quality. Creatine phosphokinase levels were lowest with a stocking density of 0.50 m(2) and the incidence of unacceptable skin damage was generally lowest with a stocking density of 0.35 m(2) and highest with 0.42 m(2). The main source of variation in this experiment was day of transport/slaughter within stocking density so that factors other than stocking density have affected the results obtained. Stocking density had a direct effect on pig behaviour during transport. Giving pigs more space during the short transport did not result in them lying down. On the contrary there was continuous disturbance from other pigs and at 0.42 and 0.50 m(2) pigs had difficulty maintaining balance, when the vehicle negotiated bends or poor road surfaces. Variations in pig behaviour during transport could account for the observed differences in skin damage. PMID- 22063073 TI - Identification and characterization of pigs prone to producing 'RSE' (reddish pink, soft and exudative) meat in normal pigs. AB - RSE (reddish-pink, soft and exudative) meat was investigated using pigs of three different halothane genotypes. A significantly lower pH(1h), value was observed in RSE compared with that of RFN (red, firm and non-exudative) -meat, both of which have values higher than 6.0 at 1 hr post-mortem. Drip loss (%) in RSE-meat was >=7%, which was twice that of RFN-meat. Normal values for fibre optic probe and Minolta L and a were observed for RSE-meat. RSE-meat could be derived from NN and Nn pigs, and its formation could be induced from RFN-prone pigs by poor post slaughter management. Pigs expected to produce RSE-meat were identified using small biopsy samples of M. longissimus dorsi (LD). Predicted RSE-meat in live pigs was confirmed by post-mortem assessments of meat quality using LD muscle. With NN Landrace-Yorkshire * Duroc pigs, 15.6% were identified to be RSE-prone in live pigs, and a further 6.7% RSE was induced after slaughter from RFN pigs. The rate of glycolysis determined from biopsy LD samples and at 1 hr post-mortem (pH(1h)) were significantly (p < 0.001) faster in RSE than in RFN-prone pigs, but significantly slower than those of PSE-prone pigs. Good correlations (p < 0.001) were observed between biopsy fluid (F) values, an indicator of water-holding capacity (WHC), and drip loss (r = 0.652) from post-mortem LD muscle, and between biopsy pH (F), an indicator for the rate of glycolysis, and F (r = -0.828). These results show that the skeletal muscle test using biopsy LD muscle could be employed to reduce the incidence of RSE-meat. PMID- 22063074 TI - A method for identification of frozen meat used for production of cooked ham. AB - A simple method to distinguish if the meat used for production of cooked hams was frozen or unfrozen was developed. Several analytical parameters of quality in meat products (general and colour parameters and protein fraction) were determined in two types of cooked hams: one elaborated with refrigerated (R) and another with frozen and thawed (F/T) raw hams. Student's t-test was applied to compare both groups, but it could not be concluded if R and F/T cooked hams had the same quality or not. For this reason two multivariate statistical analyses, Factor (FA) and Discriminant Analysis (DA), were applied. The application of FA resulted in the separation of the two groups of cooked hams and allowed the selection of the parameters which were used in Discriminant Analysis (DA). A discriminant function, that is both easy to use and to interpret, was obtained. PMID- 22063075 TI - Effect of the dietary supplementation with vitamin E on colour stability and lipid oxidation in packaged, minced pork. AB - The effect of supplementation of vitamin E (200 W kg(-1) feed) in the diet of pigs on colour stability and lipid oxidation in minced pork was studied. Control and enriched diets were provided for the last 12 weeks before slaughter. Half of the samples of minced shoulder meat from control and supplemented pigs were packaged on trays with oxygen-permeable overwraps and half in modified atmosphere packs (initial gas mixture: O(2)/CO(2)/N(2) = 66/ 27/7). Meats were stored for 10 days at 7 degrees C in an illuminated retail display cabinet. The meat from vitamin E-supplemented pigs was more resistant to lipid oxidation than was the control meat. Gas packaging appeared to increase lipid oxidation in control meat, whereas lipid oxidation was stable in meat from vitamin E-supplemented pigs. Colour stability for gaspacked meat was comparable for both dietary groups. However, oxygen-permeable overwraps had a negative effect on colour stability in vitamin E-enriched meat. The reason for this is not known. The shelf-life of enriched and control meat was similar. Thus supplementation of pig feeds with vitamin E is recommended if an improved stability against lipid oxidation of (minced) pork is required. PMID- 22063076 TI - Random amplified polymorphic DNA (RAPD) fingerprints for identification of red meat animal species. AB - The random amplified polymorphic DNA (RAPD) method was used to generate fingerprint patterns for 10 meat species: wild boar, pig, horse, buffalo, beef, venison, dog, cat, rabbit and kangaroo. A total of 29 10-nucleotide primers, with GC contents ranging from 50-80%, were evaluated for their specificity and efficiency. The fingerprint patterns that were generated were found in some cases to be species-specific, i.e. one species could be differentiated from another. The advantages and disadvantages of using RAPD-PCR for the identification of red meat species are also discussed. PMID- 22063077 TI - Effects of age and/or weight at slaughter on longissimus dorsi muscle: Biochemical traits and sensory quality in pigs. AB - The effect of increasing either age alone through feed restriction, or both age and weight at slaughter, on the quality of the longissimus dorsi muscle (LM) was investigated. Starting at 83 days of age and 32 kg, 80 pigs were allotted within litter to four experimental groups. All pigs were free of RYR1 mutated gene. Pigs were fed either ad libitum (A100, A130) or restricted 30% (R100, R130) and slaughtered at either 100 kg (A 100, R100) or 130 kg (A130, R130) body weight. Restricting feed intake in order to increase age at the same weight resulted in slower growth, better feed efficiency and increased leanness, whereas increasing age and weight simultaneously elicited slower growth, reduced feed efficiency and fatter carcasses. Intramuscular fat (IMF) and muscle collagen concentration were reduced by restricted feeding. Increase in both age and weight of pigs resulted in lower water, and higher protein and IMF concentrations. Although pigs were free of RYR1 gene, the PSE condition (defined as pH1 <= 5.9) developed in 25 carcasses, with a higher incidence in restricted pigs. PSE animals were excluded from the subsequent analysis of meat quality data. Feed restriction resulted in higher drip loss and lower a(*) and c(*) (saturation index) values. Longer myofibril fragments in muscle of restricted pigs on day 1 post mortem are indicative of slower maturation, while longer fragments on day 4 in heavier pigs, suggest that the extent of post mortem tenderisation could be negatively affected by the elevation of slaughter weight. Feed restriction had no significant effect on meat sensory quality, whereas increase in both age and weight resulted in lower tenderness, chewiness and mouth coating scores. Our results indicate that increasing age at a given body weight, via feed restriction, reduced IMF and collagen concentrations, and the rate of post mortem proteolysis, however, this had no significant impact on pork quality assessed after 4 days of ageing. On the other hand, increasing both age and weight at slaughter could alter pork texture, in spite of elevated IMF concentration. PMID- 22063079 TI - Letter to the editor: Initial toughness of meat. PMID- 22063078 TI - Effect of dietary fat and vitamin E on colour stability and on lipid and protein oxidation in Turkey meat during storage. AB - The objectives of the study were to investigate the effects of dietary fat (6% soya oil or rapeseed oil or tallow), together with tocopheryl acetate at either a basal (30 ppm) or a supplemented (400 ppm) level for 16 weeks on lipid and protein oxidation, including myoglobin, during refrigerated storage of turkey muscles. When turkeys were fed tallow in particular, vitamin E supplementation improved the vitamin E status of the muscles. Vitamin E supplementation significantly delayed lipid oxidation measured by TBARS, whatever the dietary fat. TBARS were highest in meat from animals fed soya oil. Vitamin E supplementation had no positive effect on colour stability of meat during refrigerated storage. Feeding soya oil induced significantly higher oxidation of proteins (carbonyl content) than rapeseed oil or tallow and vitamin E supplementation induced a slight decrease in carbonyl content at day 9 of storage for M. sartorius. SH content was significantly higher in vitamin E supplemented M. sartorius and M. pectoralis than in controls. PMID- 22063080 TI - Systemic thrombolytic therapy in acute ischemic stroke--new experiences in spreading network of stroke units in Croatia. AB - BACKGROUND: The aims of this paper are: 1) to present the data of systemic thrombolysis for ischemic stroke in five Croatian centers from July 2008 till January 2010; 2) to compare the results between centers and; 3) to compare data with previously published results from 2006 to 2008 period from our center, and with the data from SITS (Safe Implementation of Treatments in Stroke). METHODS: We retrospectively reviewed the medical data of thrombolysed patients in following hospitals: University Hospital Center Zagreb (91 patients), University Hospital Split (25 patients), University Hospital Osijek (22 patients), General Hospital Varazdin (21 patient), and General Hospital Zadar (7 patients). RESULTS: The "time to door" for all centers was 79.71+/-38.63 min, the "door to needle" period was 64.39+/-24.18 min. Systolic and diastolic blood pressures at admission were 158.65+/-27.72 and 90.18+/-15.03 mm Hg, respectively. Systolic and diastolic blood pressures measured immediately prior to administering rt-PA were 152.19+/ 23.17 and 85.40+/-15.27 mm Hg, respectively. Initial median NIHSS score was 12, median NIHSS 2h post thrombolysis was 8, and 7th day after rt-PA treatment 4. Intracerebral hemorrhages or secondary hemorrhagic transformations occurred in 21 (12.65%) patients, among which nine were symptomatic. In a 4.5h time window total of 17 patients were thrombolysed. We did not find any differences in outcome between this group and group of patients thrombolysed in the 3h time-window. The group of patients older than 80 years had a worse outcome. CONCLUSIONS: According to our data, treatment with rt-PA is safe, feasible and effective for stroke patients in both university as well as regional hospitals having stroke units established. Organization of stroke units in regional hospitals, as well as systematic education of public health workers and neurologists, leads to the possibility for each patient to reach the nearest stroke unit and gets the thrombolytic therapy in the therapeutic time window. PMID- 22063081 TI - Late onset vanishing white matter disease presenting with learning difficulties. AB - BACKGROUND: Vanishing white matter is an inherited leukoencephalopathy with typical childhood onset. Late onset forms are rare and may present with an extended range of phenotypes. Case report We present a patient born to consanguineous parents who developed learning disabilities by the age of 16 years. At the age of 25 she had a focal motor seizure with subsequent hemiparesis. After an extensive investigation she was diagnosed and treated as multiple sclerosis. There was progressive memory and planning impairment and, six years later, Sjogren syndrome with central nervous system involvement was diagnosed. For six months she was treated with cyclophosphamide, without any improvement. The next two years she had major clinical deterioration following infections. A homozygous mutation was identified in the EIF2B5 gene at the age of 33, and she died a year later. CONCLUSIONS: VWM leukoencephalopathy is still largely recognized as a pediatric disorder, with many adult neurologists being unfamiliar with the late onset presentations. We wish to draw attention into these forms, avoiding submitting these patients to extensive workup and unnecessary treatments. PMID- 22063082 TI - Recovery of myocardial tissue from extracted leads. PMID- 22063083 TI - The value of in silico chemistry in the safety assessment of chemicals in the consumer goods and pharmaceutical industries. AB - In silico toxicology prediction is an extremely challenging area because many toxicological effects are a result of changes in multiple physiological processes. In this article we discuss limitations and strengths of these in silico tools. Additionally, we look at different parameters that are necessary to make the best use of these tools, and also how to gain acceptance outside the modelling community and into the regulatory arena. As a solution, we propose an integrated workflow for combined use of data extraction, quantitative structure activity relationships and read-across methods. We also discuss how the recent advances in this field can enable transition to a new paradigm of the discovery process, as exemplified by the Toxicity Testing in the 21st Century initiative. PMID- 22063084 TI - Cholesterol content and fatty acid composition of rhea meat. AB - The influence of species and muscle on the intramuscular fat content, cholesterol content and fatty acid composition of Greater and Lesser Rhea meat were evaluated. Muscle has no influence (P>0.05) on any of these characteristics. Neither intramuscular fat (1.23%) nor cholesterol content (57 mg/100 g) differed (P>0.05) between species. Despite differences (P<0.05) in the percentage of individual fatty acids, total saturated fatty acids (33.1%) did not differ (P>0.05) between species, while total monounsaturated fatty acids (26.8 vs 32.2%) was lower (P<0.05) and total polyunsaturated fatty acids (39.7 vs 33.6%) higher (P<0.05) for Greater than Lesser Rhea. PMID- 22063085 TI - Consumer perception, facts and possibilities to improve acceptability of health and sensory characteristics of pork. AB - Changes at consumer level, as well as an image decline of the meat sector, resulted in considerable decreases of fresh meat consumption. Consumer orientation is considered as a prerequisite to slow down or reverse the adverse fresh pork consumption evolution. Consumer perception of pork is taken as the starting point of this article. Focus is first on assessing differences between facts related to nutritional value and healthiness aspects of pork and their perception by Belgian meat consumers. Second, possibilities of improving pork characteristics are identified. Pork is perceived worst as compared to beef and poultry on the attributes leanness, healthiness, taste and tenderness. Consumer oriented response strategies should focus at improving these intrinsic quality characteristics, before other elements like traceability, labelling or marketing can be implemented successfully. The possibilities to improve nutritional value, healthiness and sensory characteristics pertain to selection, pig diet composition, transport, slaughter and post-slaughter circumstances. A successful adoption of consumer orientation urges for co-operation throughout the entire pork production chain. The identified topics are key attention points for adequate production and marketing by the pork sector, as well as for consequent communication by government and public services. PMID- 22063086 TI - The effect of stress, applied immediately before stunning, on pork quality. AB - The effect on meat quality characteristics of stress, applied during a short period just before stunning, was studied on slaughterpigs (113 boars, 85 gilts). Sexes were kept separately and only pigs that had been stunned correctly were included. Aggressive behaviour during lairage occurred more frequently in boars (about twice) than in gilts. Just before stunning, two animals of the same sex, that were lairaged for an equal period at the slaughter facility, were moved as quietly as possible to the stunning pen, after which one pig was stunned immediately and the other subsequently forced to move through the stunning pen over a period of 1 min. Stress resulted in lower pH values and higher temperatures in the semimembranosus (SM) and the longissimus lumborum (LL) muscles and a higher rigor mortis value of the SM, at 45 min post mortem. Stress affected water holding capacity of the LL negatively at 24 h p.m. Statistically significant interactions were present for sex*stress for several meat quality traits. In general, gilts reacted more strongly to short periods of stress than did boars. PMID- 22063087 TI - Changes in connective tissue of M. semitendinosus as a response to different growth paths in steers. AB - The effect of growth path, as opposed to advancing age, on the biophysical and biochemical properties of muscle connective tissue was investigated. Nine-month old Brahman-cross steers were grown across either an uninterrupted path, or paths that incorporated weight-loss and then weight gain on two different diets: one group was realimented on pasture, whilst the other was realimented on a grain based diet. Biophysical attributes of connective tissue toughness (Compression and Adhesion) in the semitendinosus muscle, were significantly reduced by treatment (P<0.05): weight loss with grain realimentation being the least tough in regard to the connective tissue component. Variance within the biophysical attributes was modelled statistically. Statistically significant models included terms for the post-slaughter connective tissue content as well as tissue contents of the enzymes lactate dehydrogenase and isocitrate dehydrogenase. The data suggest that biochemical measurements made up to 100 days prior to slaughter, may have value as indicators of final connective tissue toughness. PMID- 22063088 TI - Effect of the type of diet on muscle characteristics and meat palatability of growing Salers bulls. AB - The effect of the type of diet (hay vs grass silage) on body composition and characteristics and palatability of semitendinosus (ST) and longissimus thoracis (LT) muscles of 16 month old Salers bulls fed at the same energy levels were studied. Animals fed hay had a lower daily weight gain and carcass weight and were leaner. There were no significant differences in the proportions of fibre types in the ST or LT due to diet. ST muscle of hay fed animals had a lower oxidative metabolism, but contained similar amounts of total and type I collagen and greater amounts, and proportions of soluble collagen and of type III collagen, than those of animals fed grass silage. ST muscles of hay-fed animals were more tender than those of silage-fed animals. PMID- 22063089 TI - Effects of electrical stimulation on early postmortem muscle pH and temperature declines in pigs from different genetic lines and halothane genotypes. AB - The objective of this study was to determine if electrical stimulation (ES) early postmortem is an effective method to generate PSE-like meat. One hundred and thirty-eight gilts (85-125 kg) from heavy muscled (HM), normal muscled (NM), and light muscled (LM) porcine genetic lines were subjected to one of two treatments: ES (26 pulses of 500 V, 60 Hz) at 3 min postmortem or non-stimulated (NS). Pigs from HM line were further characterized as halothane (HAL) carriers (Nn) or non carriers (NN). ES carcasses had lower (P<0.0001) pH values and higher (P<0.0001) temperature than NS carcasses during the first 56 min postmortem. ES carcasses had lower (P<0.0001) a*-values, and color and firmness scores, as well as higher (P<0.0001) drip loss and L*-values. No significant interactions were found between treatment and genetic line or HAL gene status with regard to pH, temperature, or quality characteristics. Temperature and pH declines within the first hour postmortem were not affected by genetic line, but slight (P<0.01) quality differences were observed. Nn and NN did not differ in pH or temperature within the first hour postmortem, but Nn carcasses had lower (P<0.01) color and firmness scores, and higher (P<0.05) drip loss. These results show that ES early postmortem is an effective method for simulating PSE development in pigs of different muscling and HAL gene status, and suggest that pH and temperature decline alone cannot explain all aspects of pork quality. PMID- 22063090 TI - Optical measurements of pH in meat. AB - The pH changes occurring in a carcass during the first 24 h after slaughter are important for the quality of the final meat or meat products. Protein denaturation will occur if pH falls to too low a level or if a relatively low pH sets in at a time after slaughter where the carcass temperature is still high. This will result in meat with poor water holding capacity and in extreme cases in meat that is PSE. pH is measured electrochemically using either glass or solid state (IS-FET) electrodes. However, electrochemically based methods are slow to use and do not offer good precision on unhomogenized meat. In this work it has been investigated whether pH can be measured spectroscopically in reflectance using the visual and near infrared spectral regions. On a limited number of pig meat samples (46 longissimus dorsi and 46 semimembranosus muscles) correlations of 0.85 have been achieved using the fast spectroscopic techniques opposed to glass electrode measurements done in duplicate. The prediction errors for the spectroscopic techniques are found to be comparable to the precision of the reference method. PMID- 22063091 TI - Hind-limb protein metabolism and calpain system activity influence post-mortem change in meat quality in lamb [Meat Science 52(1) 9-18]. PMID- 22063092 TI - Bayesian inference in FMRI. AB - Bayesian inference has taken FMRI methods research into areas that frequentist statistics have struggled to reach. In this article we will consider some of the early forays into Bayes and what motivated its use. We shall see the impact that Bayes has had on haemodynamic modelling, spatial modelling, group analysis, model selection and brain connectivity analysis; and consider how these advancements have spun-off into related areas of neuroscience and some of the challenges that remain. Bayes has brought to the table inference flexibility, incorporation of prior information, adaptive regularisation and model selection. But perhaps more important than these things, is the ability of Bayes to empower the methods researcher with a mathematically principled framework for inferring on any model. PMID- 22063093 TI - The future of ultra-high field MRI and fMRI for study of the human brain. AB - MRI and fMRI have been used for about three and two decades respectively and much has changed over this time period, both in the quality of the data and in the range of applications for studying the brain. Apart from resolution improvements from around 4mm in the early days to below 0.5mm with modern technology, novel uses of contrast have led to the ability to sensitize images to some of the brain's structural properties at the cellular scale as well as study the localization and organization of brain function at the level of cortical columns. These developments have in part been facilitated by a continuing drive to increase the magnetic field strength. Will the next few decades see similar improvements? Here we will discuss current state of high field MRI, expected further increases in field strength, and improvements expected with these increases. PMID- 22063094 TI - Greater corticolimbic activation to high-calorie food cues after eating in obese vs. normal-weight adults. AB - The goal of this research is to identify the neural response to rewarding food cues before and after eating in overweight/obese (OB) and normal-weight (NW) adults. Based on the previous literature, we expected greater differential activation to food cues vs. objects for OB compared to NW participants both prior to eating and after consumption of a typical lunch. Twenty-two overweight/obese (11 male) and 16 normal-weight (6 male) individuals participated in a functional magnetic resonance imaging task examining neural response to visual cues of high- and low-calorie foods before and after eating. The OB group demonstrated increased neural response to high- and low-calorie foods after eating in comparison to the NW participants in frontal, temporal, and limbic regions. In addition, greater activation in corticolimbic regions (lateral OFC, caudate, anterior cingulate) to high-calorie food cues was evident in OB vs. NW participants after eating. These findings suggest that for OB individuals, high calorie food cues show sustained response in brain regions implicated in reward and addiction even after eating. Moreover, food cues did not elicit similar brain response after eating in the NW group suggesting that neural activity in response to food cues diminishes with reduced hunger for these individuals. PMID- 22063095 TI - Domain flexibility modulates the heterogeneous assembly mechanism of anthrax toxin protective antigen. AB - The three protein components of anthrax toxin are nontoxic individually, but they form active holotoxin complexes upon assembly. The role of the protective antigen (PA) component of the toxin is to deliver two other enzyme components, lethal factor and edema factor, across the plasma membrane and into the cytoplasm of target cells. PA is produced as a proprotein, which must be proteolytically activated; generally, cell surface activation is mediated by a furin family protease. Activated PA can then assemble into one of two noninterconverting oligomers, a homoheptamer and a homooctamer, which have unique properties. Herein we describe molecular determinants that influence the stoichiometry of PA in toxin complexes. By tethering PA domain 4 (D4) to domain 2 with two different length cross-links, we can control the relative proportions of PA heptamers and octamers. The longer cross-link favors octamer formation, whereas the shorter one favors formation of the heptamer. X-ray crystal structures of PA (up to 1.45 A resolution), including these cross-linked PA constructs, reveal that a hinge-like movement of D4 correlates with the relative preference for each oligomeric architecture. Furthermore, we report the conformation of the flexible loop containing the furin cleavage site and show that, for efficient processing, the furin site cannot be moved ~5 or 6 residues within the loop. We propose that there are different orientations of D4 relative to the main body of PA that favor the formation of either the heptamer or the octamer. PMID- 22063096 TI - Cross-monomer substrate contacts reposition the Hsp90 N-terminal domain and prime the chaperone activity. AB - The ubiquitous molecular chaperone Hsp90 plays a critical role in substrate protein folding and maintenance, but the functional mechanism has been difficult to elucidate. In previous work, a model Hsp90 substrate revealed an activation process in which substrate binding accelerates a large open/closed conformational change required for ATP hydrolysis by Hsp90. While this could serve as an elegant mechanism for conserving ATP usage for productive interactions on the substrate, the structural origin of substrate-catalyzed Hsp90 conformational changes is unknown. Here, we find that substrate binding affects an intrinsically unfavorable rotation of the Hsp90 N-terminal domain (NTD) relative to the middle domain (MD) that is required for closure. We identify an MD substrate binding region on the interior cleft of the Hsp90 dimer and show that a secondary set of substrate contacts drives an NTD orientation change on the opposite monomer. These results suggest an Hsp90 activation mechanism in which cross-monomer contacts mediated by a partially structured substrate prime the chaperone for its functional activity. PMID- 22063097 TI - The use of high resolution melting analysis to detect Fabry mutations in heterozygous females via dry bloodspots. AB - BACKGROUND: As an X-linked genetic disorder, Fabry disease was first thought to affect males only, and females were generally considered to be asymptomatic carriers. However, recent research suggests that female carriers of Fabry disease may still develop vital organ damage causing severe morbidity and mortality. In the previous newborn screening, from 299,007 newborns, we identified a total of 20 different Fabry mutations and 121 newborns with Fabry mutations. However, we found that most female carriers are not detected by enzyme assays. METHODS: A streamlined method for high resolution melting (HRM) analysis was designed to screen for GLA gene mutations using a same PCR and melting program. Primer sets were designed to cover the 7 exons and the Chinese common intronic mutation, IVS4+919G>A of GLA gene. RESULTS: The HRM analysis was successful in identifying heterozygous and hemizygous patients with the 20 surveyed mutations. We were also successful in using this method to test dry blood spots of newborns afflicted with Fabry mutations without having to determine DNA concentration before PCR amplification. CONCLUSION: The results of this study show that HRM could be a reliable and sensitive method for use in the rapid screening of females for GLA mutations. PMID- 22063098 TI - Sarcoid reactions in the skin: 3 cases in association with B-cell lymphomas. PMID- 22063099 TI - Effects of dietary fats on meat quality and sensory characteristics of heavy pig loins. AB - This study examined the influence of dietary fat supplementation to heavy pigs on the meat quality and sensory characteristics of loins. The animals were fed diets containing tallow (TA), corn oil (CO) or rapeseed oil (RO) from 25 kg up to 160 kg live weight (LW). The fats were added at 3% as fed from 25 to 110 kg LW, and at 2.5% from 110 kg LW to slaughtering. Diets were fed at 9% BW(0.75). We found no differences between dietary treatments for loin weight, pH, or color of longissimus lumborum (LL) muscle at 45 min and 24 h after slaughtering. No significant differences in moisture, total protein or total lipid content of LL muscle were found. The linolenic acid content of the total lipid of LL muscle was higher in pigs fed RO than those fed TA and CO. The oxidative stability of LL, as determined by induced TBARS, was lower in pigs fed CO - after 60 min of forced oxidation - and in animals fed CO and RO after 300 min, compared to those fed TA. No significant differences in the sensory characteristics of loin were discerned by a panel of trained tasters. These results indicate that long-term nutrition with added fat at the levels we used has little or no effect on the meat quality or sensory characteristics of heavy pig loin. PMID- 22063100 TI - Effect of dietary conjugated linoleic acid, irradiation, and packaging conditions on the quality characteristics of raw broiler breast fillets. AB - Skinless breast fillets were harvested from broilers fed with 0, 0.25, 0.5, or 1.0% conjugated linoleic acid (CLA) for 3 weeks. Fillets were either vacuum or aerobically packaged, then irradiated at 0 or 3.0 kGy using a Linear Accelerator. Breast fillets were analyzed for thiobarbituric acid reactive substances (TBARS), volatile profiles, and color at 0 and 7 days of storage at 4 degrees C. Dietary CLA reduced TBARS, but had no effect on volatile profiles and color of breast fillets. Color a* value of breast fillets increased after irradiation. Irradiation also induced production of many volatiles, mainly alkanes and alkenes, which could be the breakdown products of unsaturated fatty acids and amino acids. High amount of dimethyl disulfide was detected in the volatiles of irradiated fillets. Low level of hexanal and pentanal in volatiles, together with low TBARS values, indicated that lipid oxidation of breast fillets after irradiation is not a big concern. PMID- 22063101 TI - Effects of RN genotype and silage feed on fat content and fatty acid composition of fresh and cooked pork loin. AB - This study aimed to establish effects of RN genotype and feed (red clover silage) on intra muscular fat content (IMF) and fatty acid composition (FA) of fresh and cooked pork loin (M. longissimus dorsi). Raw loins from silage-fed pigs compared with those from conventionally fed pigs had lower IMF, lower relative levels (rel.%) of saturated (SAFA) and monounsaturated (MUFA) fatty acids, and higher rel.% of polyunsaturated fatty acids (PUFA, omega6, omega3). Cooked loins, from silage-fed pigs compared with those of conventionally fed pigs, had higher rel.% of omega3, and lower omega6/omega3 ratios. IMF and cooking influenced FA concentrations in a pork portion. The differences in concentrations of SAFA, MUFA, PUFA and omega6 between raw loins of silage-fed pigs and conventionally fed pigs did not remain in cooked loins. The omega6/omega3 ratio, however, remained low, and thus more beneficial in loins from silage-fed pigs after cooking. PMID- 22063102 TI - Carbon monoxide-heme pigment is responsible for the pink color in irradiated raw turkey breast meat. AB - Turkey breast muscles were aerobically or vacuum packaged, irradiated at 0, 2.5, or 5.0 kGy using a Linear Accelerator (electron beam), and stored at 4 degrees C. The CIE color values, reflectance scan, oxidation-reduction potential (ORP), production of gaseous compounds, and lipid oxidation of samples were determined at 0, 1, and 2 weeks of storage. Absorption spectra of sample drips were determined at 1 week of storage. Irradiation increased the a-value of both aerobically and vacuum-packaged turkey breast, but vacuum-packaged meat had stronger intensity than the aerobically packaged. The increased redness in vacuum packaged meat was stable during the 2 weeks of storage. The production of CO in meat, which can bind to myoglobin as a sixth ligand, was proportional to irradiation dose. The ORP was decreased by irradiation, but was increased during storage. The ORP and lipid oxidation values were lower in vacuum-packaged than those in aerobically packaged turkey breast. Therefore, increased a-values in irradiated turkey breast should be caused by the decreased ORP and heme pigment CO ligand formation. The absorption spectra of meat drip also showed that the peak wavelengths of irradiated turkey breast were similar to that of the CO myoglobin. PMID- 22063103 TI - Effect of vitamin E supplementation on alpha-tocopherol and beta-carotene concentrations in tissues from pasture- and grain-fed cattle. AB - The effects of dietary vitamin E supplementation of grain-fed cattle on lipid oxidation and meat colour have been extensively investigated, but little attention has been given to pasture-fed cattle where meat is likely to contain naturally high amounts of alpha-tocopherol and carotenoids. In the work described, we evaluated the effects of pasture-feeding alone and with vitamin E supplementation on tissue levels of anti-oxidants and compared the findings with those obtained for grain-fed cattle with and without supplementation. Sorghum was the major component of the grained-based ration. alpha-Tocopherol concentrations in plasma, muscle and fat tissues of pasture-fed cattle were not affected by vitamin E supplementation (2500 IU/head/day for 132 days prior to slaughter) while those of grain-fed cattle increased significantly. The alpha-tocopherol concentrations in the supplemented grain-fed cattle were similar in muscle and liver to pasture-fed animals but were lower in their fat (P<0.05). The major carotenoid present in all tissues studied from pasture-fed was beta-carotene and its contents in plasma, liver, fat and muscles were decreased (P<0.05) by supplementation with vitamin E. Carotenoids were essentially absent in grain-fed cattle except for small amounts in liver. The implication of this study for the meat industry is that cattle grazed on good pasture can achieve concentrations of alpha-tocopherol in muscles and other tissues at least as high as those obtained by supra-nutritional supplementation of grain-fed cattle with vitamin E. However, alpha-tocopherol supplementation of pasture-fed cattle reduced tissue concentrations of beta-carotene, which would reduce carcase fat yellowness and make pasture-fed cattle more acceptable to some Asian markets. PMID- 22063104 TI - Lipid stability and meat colour of beef from pasture- and grain-fed cattle with or without vitamin E supplement. AB - Meat from pasture-fed cattle can have high contents of alpha-tocopherol and other anti-oxidants originating from naturally occurring compounds present in grasses. However, meat from pasture-fed cattle may have an increased demand for endogenous anti-oxidants because of its high content of polyunsaturated fatty acids, which in turn, may affect its colour and lipid stability. In the work described, we evaluated the effects of pasture-feeding alone and with vitamin E supplementation and compared the findings with those obtained for grain-fed cattle (predominantly sorghum) with and without supplementation. Within each nutritional background, vitamin E supplementation did not alter meat colour or colour stability of fresh or 47-day aged muscle during 7-day aerobic storage. However, both control and supplemented grain-fed product had better meat colour (more redness) compared with meat from grass-fed cattle. These differences in redness between pasture- and grain-fed fresh beef were not apparent after ageing. The treatments did not affect the lipid stability of fresh meat during aerobic storage; however, supplementation reduced (P<0.01) lipid oxidation in grain-fed aged beef compared with pasture-fed aged beef, despite both having similar alpha-tocopherol contents. Pasture-fed beef had more linolenic acid, less linoleic acid and, overall, was more polyunsaturated than grain-fed beef (P<0.05). In summary, vitamin E supplementation of pasture-fed cattle did not alter muscle tocopherol contents but pasture-fed beef (both control and supplemented) was more susceptible to lipid oxidation following ageing than vitamin E supplemented grain fed beef. PMID- 22063105 TI - Electrical impedance and tenderisation in bovine meat. AB - The electrical properties and the muscle fibre mechanical resistance of different beef muscles were measured between 1 and 14 days post-mortem. Electrical measurements used different electrode types working by contact with or penetration of muscle. Measurements from the different electrode types were strongly correlated (0.83< r(2) <0.96). Both impedance (Z) and the ratio Z(1 kHz)/ Z(100 kHz) decrease during ageing. These parameters show an almost linear relationship with muscle fibre mechanical resistance. However, the slope of these curves for one muscle changed among animals. Therefore, these electrical parameters are not useful for the prediction of the state of ageing. Meat electrical anisotropy decreases both when frequency increases and with ageing. Electrical anisotropy measured at 1 kHz is significantly (r=0.59, N=129 P<0.01) correlated to muscle fibre mechanical resistance. The mean anisotropy decreases linearly with muscle fibre mechanical resistance in the same way for Semimembranosus and Pectoralis Profundus muscles. When meat is fully aged it is almost electrically isotropic. Electrical anisotropy is, therefore a potential parameter to evaluate meat ageing, but improvements in accuracy are needed before it can be used. PMID- 22063106 TI - Comparison of CO(2) stunning with manual electrical stunning (50 Hz) of pigs on carcass and meat quality. AB - The effects of carbon dioxide stunning on carcass and pork quality attributes were compared with the effects of manual electrical stunning using either head only or head-to-brisket electrodes. A total of 30 Large White*Landrace boars (homozygous dominant for the halothane gene) were randomly allocated immediately prior to slaughter to one of three stunning treatments: carbon dioxide (90% CO(2)), head only (HO; 1.3 A for 4 s at a frequency of 50 Hz) or head to brisket (HBR; 1.3 A for 4 s at a frequency of 50 Hz) electrical stunning. The pH of the M. longissimus thoracis (LT) muscle measured at two sites [between the fifth and sixth thoracic vertebrae (Site 1) and the last thoracic rib (Site 2)] at 40 min post-slaughter was lower (P<0.001) in HBR stunned pigs compared with both CO(2) and HO stunned pigs. No differences in ultimate pH of the LT at either measurement site were found due to stunning method. However, a faster (P<0.05) relative rate of pH decline was found in the LT at Site 1 from HBR stunned pigs compared with CO(2) stunned pigs. No difference in the relative rate of muscle pH decline (P>0.05) between stunning methods was found in the LT muscle at Site 2. Pork from HBR stunned pigs was paler (P<0.05) and had a higher (P<0.001) percentage drip loss compared with pork from HO and CO(2) stunned pigs. LT muscles from HBR stunned pigs had lower (P<0.001) WB shear force values compared with pork from HO stunned pigs (6.57 vs. 8.12 kg, S.E.D. 0.49). Carcass quality was improved by CO(2) stunning, with less (P<0.05) ecchymosis-affected pork trimmed from shoulder primals compared with electrically stunned pigs. These results indicate that manual electrical stunning of pigs using HO tongs and CO(2) stunning reduced percentage drip loss, reduced muscle lightness and reduced the rate of muscle pH decline compared with pigs manually electrically stunned using HBR tongs. PMID- 22063107 TI - Sexing of beef - a survey of possible methods. AB - The beef trade, amounting to several billion Euro per year, is of great importance in the European Union. Several measures have been introduced to support beef producers, such as intervention buying. However, these payments are only effected for male beef, which represents a temptation for fraud. Consequently, reliable methods for sexing of beef are required. This report summarises existing methods in EU countries as well as possible alternatives deduced from the literature. Individual methods are discussed for their advantages and disadvantages as well as their general applicability. PMID- 22063108 TI - Analysis of raw meat to predict proteolysis in Parma ham. AB - Four hundred and thirty-seven pigs (223 purebred Italian Large White, 97 Italian Landrace, and 117 Duroc), were studied to examine the effect of breed on meat quality and assess the possibility of relating proteolysis of dry-cured hams to raw meat quality. The Duroc pigs had intramuscular fat contents and water holding capacities (M. Semimembranosus) significantly higher than those of the Large White and Landrace. The latter had a significantly higher pH(24h) and cathepsin B activities significantly lower than the Duroc breed. The dry-cured hams (M. Biceps femoris) from the three breeds were significantly different in proximate composition, proteolysis and weight loss at the end of ageing. Data for green hams (including salt content) were used to compute a model to fit the proteolysis of the corresponding dry-cured hams. The variables included in the model (R(2)=0.53 and P<0.01) were cathepsin B activity of raw ham, pH(24h), weight loss after the first salting step, and the salt content of the dry-cured ham. The raw hams with the highest cathepsin B activities, the lowest pH(24h), and the highest weight loss after the first salting were those in which greatest proteolysis occured. PMID- 22063109 TI - A comparison of biochemical and meat quality variables in red deer (Cervus elaphus) following either slaughter at pasture or killing at a deer slaughter plant. AB - To investigate effects of pre-slaughter handling on blood and muscle biochemistry and venison quality, paddock-shot (n=8) and commercially slaughtered red deer (n=8) were compared. The deer were kept in two larger groups. One stag per group per day was head-shot, exsanguinated, electrically stimulated then transported 150 m to a deer slaughter premises (DSP) for processing. Prior to each slaughter day one of the groups was mustered into a deer yards and six (including two experimental) deer were selected for commercial handling and processing (including electrical stimulation) at the same DSP. Blood samples taken during exsanguination showed higher levels of cortisol, progesterone, glucose, lactate, albumin, creatine kinase, lactate dehydrogenase, aspartate aminotransferase and packed cell volume in the DSP-killed deer compared with the paddock-shot deer (P<0.05). Interpretation of these values indicated that pre-slaughter handling created moderate stress and high levels of muscular exertion or damage, possibly related to antagonism during lairage. However muscle glycogen, pH and meat quality measurements showed only minor, muscle-specific differences between treatments. PMID- 22063110 TI - The effect of genotype, sex and management strategy on the eating quality of pork. AB - Two hundred and sixteen (Large White*Landrace*Duroc) crossbred pigs were used to determine the influence of genotype, sex, and management strategies on pork quality. The experiment was a 2*3*3 factorial design with the main treatments being genotype (A - 50% and B - <25% Duroc bloodline), sex (females, surgical barrows and immunological barrows) and management strategy (control - C, dietary conjugated linoleic acid supplementation - CLA, and porcine somatotropin administration - pST). Genotype A pigs had less backfat (P2 site), higher intramuscular fat percentage, higher muscle ultimate pH (pH(u)) and surface exudate, and the pork was tougher and less acceptable compared with Genotype B pigs. Female pigs had lower muscle pH(u), higher surface exudate and tougher pork compared with both surgical and immunological barrows. Pigs fed the control diet had lower muscle pH(u) and higher surface exudate compared with pigs fed the CLA supplemented diet or administered pST. Pigs fed the control diet had higher consumer likeness scores for flavour, tenderness, juiciness and overall acceptability compared with pigs fed the CLA supplemented diet or administered pST. The results from this experiment indicate that pork eating quality is reliant on a complex interaction between genotype and sex. The results also indicate that management strategies such as pST administration and CLA supplementation, while being effective in reducing backfat, have the potential to have a negative impact on pork quality. PMID- 22063111 TI - Determination of the precision of the fatty acid analysis of Iberian pig fat by gas chromatography. Results of a mini collaborative study. AB - A collaborative study was carried out to determine the repeatability (error in each laboratory) and reproducibility (error between the different laboratories) of the fatty acid analysis of Iberian pig fat by gas chromatography. To do this, a comparison was made, in accordance with the ISO 5725-2 procedure, of the weight percentage (%) of the main fatty acids (C16:0, C18:0, C18:1 and C18:2) in 60 samples, determined by six laboratories. The results obtained for the relative standard deviation of the repeatability (0.56, 0.49, 0.29, and 0.69%) and for the relative standard deviation of the reproducibility (3.04, 3.54, 1.78 and 2.86%) show that the accuracy obtained is adequate for this analysis method, and in the same order or even higher than that obtained by other authors in similar samples. The differences between the results obtained on using two extraction methods of liquid fat from subcutaneous adipose tissue were recorded with no significant differences being observed between them. PMID- 22063112 TI - Relationship of texture profile analysis and Warner-Bratzler shear force with sensory characteristics of beef rib steaks. AB - Cyclical texture profile analysis (TPA) parameters measured using a star-shaped probe with two cycles of 80% penetration and Warner-Bratzler shear force (WBS) were compared as predictors of objective tenderness and subjective sensory characteristics of rib steaks from 52 beef loins. The TPA parameters of hardness, cohesiveness and chewiness were negatively correlated (P<0.05) with trained panel sensory characteristics of initial tenderness (r=-0.64, -0.41, -0.62, respectively), amount of connective tissue (r=-0.57, -0.27, -0.55, respectively), overall tenderness (r=-0.68, -0.39, -0.64, respectively) and overall palatability (r=-0.56, -0.37, -0.53, respectively). These sensory characteristics were also negatively correlated (P<0.05) with WBS (r=-0.61, -0.49, -0.60, -0.56, respectively). Stepwise regression analysis generated prediction equations that included the TPA parameters of hardness and adhesiveness, which accounted for 47, 36, 51 and 38% of the variation in initial tenderness, amount of connective tissue, overall tenderness and overall palatability, respectively. Prediction equations using WBS accounted for 37, 24, 36 and 31% of the variation in initial tenderness, amount of connective tissue, overall tenderness and overall palatability, respectively. Hence, TPA explained more of the variation in subjective sensory tenderness of the rib steaks than WBS. PMID- 22063113 TI - Possible mechanism for the effect of the RN(-) allele on pork tenderness. AB - The effect of the dominant RN(-) allele on rigor development, ageing and tenderness was studied in M. longissimus dorsi (LD) from 11 heterozygous carriers and five non-carriers of the RN(-) allele. Rigor development was followed by measurements of muscle shortening, isometric tension, pH and FOP. During ageing the myofibrillar length and Warner-Bratzler shear force were measured in the meat. Sensory analysis was performed at 4 days post-mortem using a trained expert panel. It was found that the decrease in pH was faster for RN(-) carriers than non-carriers during the first 5 h post-mortem, after which the pH-time slope was similar for the two groups. This resulted in a significantly lower mean ultimate pH in LD from RN(-) carriers than non-carriers. During rigor development the isometric tension was lower in RN(-) carriers than in non-carriers, while contraction (shortening and sarcomere length) did not differ significantly between the two genotypes. The myofibrillar length, which is an indirect measure of the proteolytic activity that has occurred in the meat, was shorter for the RN(-) carriers than for the non-carriers. The difference in myofibrillar lengths between the genotypes was significant at 1 and 4 days post-mortem but not at 7 days post-mortem, which indicates that the RN(-) carriers have a higher proteolytic activity earlier post-mortem. The results from the Warner-Bratzler shear force measurements showed that the meat from the RN(-) carriers was significantly more tender, 1 and 4 days post-mortem, than the meat from the non carriers. The meat from non-carriers needed 7 days to reach the tenderness attained by that from the RN(-) carriers 4 days post-mortem. The greater tenderness in LD from RN(-) carriers than that from non-carriers was also confirmed by a sensory panel at 4 days post-mortem. In conclusion, differences observed in the course of rigor and ageing in muscle from carriers and non carriers of the RN(-) allele suggest that proteolytic action, as initiated by a more rapid fall in pH, is the most important factor governing the variation in tenderness of the two genotypes. PMID- 22063114 TI - Effect of stunning conditions on occurence of PSE defects in hams of rn+/RN(-) pigs. AB - Pigs of the same genetic type at the RN and HAL loci, i.e. rn(+)RN(-)/NN were reared in similar conditions of feeding and housing. They were slaughtered in two abattoirs (referred to as A1 and A2) using a mixture of air (30%) and CO(2) (70%), at a rate of 300 pigs per hour per slaughterline. One hundred and thirty two pigs from 11 farms were slaughtered in A1 using a corusinga restrainer and 127 pigs from 5 farms were slaughtered in A2 with the backloading technique. pH at 40 min, 2.5 h and 24 h after slaughter and colour (L*, a*, b*) at 24 h after slaughter were measured in the semimembranosus muscle. Meat quality of the ham was scored as follows: 1, no PSE-zone; 2, doubtful; 3, PSE-zones in the semimembranosus and sometimes on the internal flexor muscles; 4, PSE-zones in all the flexor muscles. The muscle pH value was higher in A2 than in A1 at 40 min post mortem (P<0.01), but not at 2.5 and 24 h. L* (P<0.001) and b* (P<0.05) were higher in A1 than in A2. There was a remarkable difference in meat quality scores, with 50% of the hams scoring 3 or 4 in A1, vs 13% in A2. Lairage time before slaughter affected (P<0.01) the pH value at 2.5 h (5.69 vs 5.93). The values of pH1 and pH2.5 decreased with increasing the meat quality score. The values of L* and b* increased markedly with the score. The results of the present study indicate that the method of bringing the slaughter pigs to the stunning device affects the frequency and importance of PSE meat in the ham. The automated driving of groups of animals to the stunning machine combined with the backloading of a nacelle, compared to a traditional system driving pigs in single file using electrical goads and a restrainer was beneficial with respect to both meat quality and animal welfare. PMID- 22063115 TI - Storage and packaging effects on sensory and color characteristics of ground beef. AB - Effects of irradiation (2 kGy) of ground beef patties from trimmings stored aerobically for 0 or 6 days on lean color, odor, and sensory attributes were investigated. Beef trimings were coarse ground and split into 2 groups. Group one was fine ground, pattied, and packaged immediately; group-two was stored 6 days then fine ground, pattied, and packaged. Irradiated beef patties had greater (P<0.05) off-odors, and off-flavors, lower (P<0.05) CIE L(*), a(*) and b(*) and saturation indexes values (P<0.05) after four days of storage at 0+/-1 degrees C. Irradiation of patties produced from trimmings aged an extra 6 days resulted in increased (P<0.05) saturation indexes and b(*) values, but not off-odors when compared to non-aged and irradiated patties. Thus, the production of irradiated beef patties should utilize beef trimmings with the shortest postmortem aging time and a dose of less than 2 kGy to minimize discoloration and off-odors. PMID- 22063116 TI - The effect of night transportation on the heart rate and skin temperature of ostriches during real transportation. AB - Literature has identified a number of stressors that have negative impacts on the welfare of ostriches during transportation. In order to maintain or improve the welfare of animals it is important to minimise or eliminate the impact of such stressors. Literature suggested that ostrich welfare during transit might be improved by using darkened vehicles. A preliminary study was carried out which measured the response of ostrich heart rate and skin temperature (indicators of stress) to transportation. Comparisons were made between transportation during the day and at night. Statistical tests suggested that heart rates and skin temperatures recorded during the night were lower than those recorded during the day. The usual response of ostriches to darkness is to sit, which provides greater stability for the bird while the transportation unit is in motion. Temperatures inside the transportation unit were significantly lower at night. This may also contribute to the lowering of heart rate and skin temperature as it reduces effects of heat stress. The conclusion has been drawn that transporting ostriches at night is potentially beneficial for the reduction of stress and maintenance of welfare. PMID- 22063117 TI - Effect of sodium citrate, carboxymethyl cellulose and carrageenan levels on quality characteristics of low-salt and low-fat bologna type sausages. AB - Quality characteristics of low-salt bologna-type sausage manufactured with sodium citrate (NAC), carboxymethyl cellulose (CMC) and carrageenan (CAR) were examined. Three levels of salt, NAC, CMC and CAR, and two levels of fat were used. Batter and sausage pH values were measured and the frying loss of sausages was analysed by frying slices in an electric grill. Firmness, juiciness, saltiness and flavour intensity of the sausages were sensorically evaluated. Altogether 20 separate sausage batches were prepared. In low-salt sausages containing less than 1.4% NaCl, the use of NAC, CAR and CMC decreased frying loss and increased saltiness. NAC and CAR also increased flavour intensity, but CMC did not. Furthermore, NAC, CAR and CMC increased the firmness of the low-salt sausage, while only NAC increased juiciness when the NaCl content was below 1.4%. NAC increases, however, the sodium content of the product. Therefore, it can be concluded that in low salt sausages no additive alone is suitable. A mixture of NAC and CAR appears to be the best combination. PMID- 22063118 TI - Physical evaluation of popped cereal snacks with spent hen meat. AB - Various blends of spent hen meat and grains (potato starch, corn starch, and rice flour) were popped using a popping machine. Lowest bulk density was observed in the snack with 1:2 ratio of meat and potato starch. Except for the popped snack with meat and rice flour, as the starch content increased, bulk density decreased gradually. Popped snacks with grains only were higher in L* value than those with meat and grains. The a* and b* values increased with increasing meat content. All popped snacks were significantly different (P<0.001) in bulk density, color, and breaking force. As the grain content of snacks increased, the size of the air cells also increased. Results of scanning electron microscopic and optical microscopic observations revealed the popping degree of snack with starch and spent hen meat was affected by the presence of meat. The optimum ratios of meat to grain for high expansion ratio were determined to be 1:2 and 1:3 of meat to corn starch and potato starch. PMID- 22063119 TI - Coupling process for plasma protein fractionation using ethanol precipitation and ion exchange chromatography. AB - Blood is one of the most polluting by-products of the meat industries. Technologies have been developed to recover the proteins contained in blood, and in this study, a process coupling chemical precipitation with ion exchange chromatography was developed to separate and purify the main protein fractions of blood plasma. Ethanol was used as the agent for precipitation and Q-HyperD was used to purify the proteins by chromatography. To monitor all the steps and operations, analytical methods of electrophoresis and HPLC were stablished to identify the fractionated proteins. The results show that this process can recover the main plasma proteins with a high degree of purity for use in the pharmaceutical and food industries. PMID- 22063120 TI - Chicken muscle homogenate gelation properties: effect of pH and muscle fiber type. AB - Gelation properties of chicken breast and thigh muscle homogenates at a protein concentration of 4.5% under different pH conditions (5.80-6.60) and those of myofibrillar proteins at a protein concentration of 2% were compared to determine the influence of muscle fibre types on gelation. The optimal gelling pH for breast muscle homogenates (pH 6.30) was slightly higher than that for thigh muscle homogenates (pH 5.80-6.30), a similar trend was found for the isolated chicken myofibrillar proteins (pH 6.00 for breast and 5.50 for leg). Similarly, the pH values at which breast muscle homogenate gels were weaker (pH<6.20) or stronger (pH?6.20) than thigh muscle homogenate gels were higher when compared with chicken breast and leg myofibrillar protein gels (pH<5.80 and pH>5.90, respectively). PMID- 22063121 TI - Genetic parameters for meat and fat quality and carcass composition traits in Iberian pigs. AB - Carcass composition and quality traits were measured in heavy Iberian pigs after extensive handling. The weights of trimmed hams, forelegs and loins were recorded on 2170-2553 pigs, intramuscular fat content in M. longissimus (IMF) on 1489 and percentages of palmitic, stearic, oleic and linoleic acids in the subcutaneous fat on 1495 pigs, slaughtered at about 160 kg live weight. For carcass traits the heritability estimates ranged from 0.28 to 0.41. Heritability estimate for IMF was 0.25 and estimates of heritability for the measured fatty acids ranged from 0.29 to 0.41. The estimated genetic correlations (rg) suggest antagonism between IMF and weights of hams (rg=-0.30) and loins (rg=-0.33) and an unfavourable positive association of premium cuts with linoleic acid content (rg: 0.31-0.57). The incorporation of meat and fat quality traits to the selection aims of the breeding scheme for Iberian pigs seems advisable. PMID- 22063122 TI - EU carcass classification system: carcass and meat quality in light lambs. AB - Sixty male Apenninica suckling lambs carcasses were studied in order to evaluate the relationship between carcass and meat quality of light lambs as evaluated according to the EU Mediterranean classification system. Increased carcass weight (6-12 kg) was accompanied by greater carcass size and compactness and reduced bone percentage. Moreover the meat quality was similar with the increase of carcass weight in terms of colour, water holding capacity and suitability for domestic storage. No differences for the examined parameters were found between carcasses classified in quality 1 and 2. The EU Mediterranean classification system appears to be unrelated to the quality of the merchandized meat. PMID- 22063123 TI - Extension of the shelf life of beef steaks packaged in a modified atmosphere by treatment with rosemary and displayed under UV-free lighting. AB - Fresh beef steaks, either sprayed on the surface with a solution of rosemary and vitamin C or not sprayed, were packaged in 70%O(2+)20%CO(2+)10%N(2) and displayed at 1+/-1 degrees C without illumination or illuminated by a standard fluorescent lamp, a low-UV, colour-balanced lamp (Promolux(r)), or the fluorescent lamp with a UV filter. Metmyoglobin formation, lipid oxidation (2-thiobarbituric acid reactive substances), instrumental colour (CIE L*, a*, b*), psychrotrophic bacterial counts (PCA) and sensory discolouration and off-odour were determined. Results showed that the use of the antioxidant mixture of rosemary and vitamin C together with the absence of UV radiation significantly reduced the rates of metmyoglobin formation and lipid oxidation, as well as microbial growth, and extended the display life from about 10 to about 20 days. PMID- 22063124 TI - Screening test to detect meat adulteration through the determination of hemoglobin by cation exchange chromatography with diode array detection. AB - A simple sample preparation procedure, consisting of an extraction step with Milli-Q water as extraction solvent for hemoglobins from meat samples, followed by a filtration step with a cellulose acetate filter, is applied. After cation exchange chromatographic separation and diode array detection, different peak patterns for extracted hemoglobins of cow, lamb or pork meat are obtained. Other heme-group containing proteins like myoglobin or cytochrome C, which could be also detected with diode array detection at 416 nm, are chromatographically separated from the hemoglobins. By the use of these characteristic peak patterns, the species of the meat can be specified permitting the qualitative assessment of meat adulteration with the proposed screening method. PMID- 22063125 TI - Acceptability of boar meat by consumers depending on their age, gender, culinary habits, and sensitivity and appreciation of androstenone odour. AB - Sensitivity of the consumers to androstenone, evaluated as the degree of smell (strong/weak) perceived by smelling the pure compound, is important in determining their acceptability of pork with different levels of androstenone and skatole. However, 8% (3.3% women and 16.2% men) of highly sensitive consumers like this odour, and 12.7% (9.1% women and 15.9% men) of mildly sensitive/insensitive consumers dislike it. The effect of the appreciation (like/dislike) of the smell in the acceptability of pork samples has not been reported previously. The aim of this paper is to ascertain if this liking for androstenone odour affects pork acceptability as well as the gender, age, and culinary habits of the consumers. Consumers evaluated the flavour and odour of five cooked and reheated samples, and recorded their acceptability on a 7-step scale. Results showed that acceptability of pork increases when the frequency of cooking and eating fresh pork are higher. The acceptability also differed depending on the sensitivity of the consumer within each age group. Appreciability of androstenone odour discriminates more than sensitivity in consumers' acceptance of pork. PMID- 22063126 TI - Quality characteristics of Chinese sausages made from PSE pork. AB - Chinese sausages made from normal and different levels of PSE pork (100% Normal, 50%Normal+50% PSE and 100% PSE) were vacuum-packaged and stored at 4 degrees C for 45 days. The composition, processing yield, pH value, thiobarbituric acid (TBA) value, water activity, lactic acid bacteria counts and sensory properties of the meat products were evaluated. PSE pork loins had lower pH value, water holding capacity, moisture, fat and myofibrillar proteins content, but higher L(*) value, drip loss and protein content than normal pork. Sausages made from 100% PSE pork had lower pH value, processing yield, moisture and fat content, but higher protein content than those of the 100% Normal and the 50% Normal+50% PSE treatments. Water activity was higher in the 100% PSE treatment than in other treatments. No differences in lactic acid bacterial counts among these treatments were observed. The pH values and water activity of the meat samples decreased, while lactic acid bacterial counts increased with storage time. TBA values among these treatments were not significantly different; however, the increase% of TBA values was higher for the 100% PSE treatment. TBA values of all treatments remained relatively low during storage. Chinese sausages made with 50-100% PSE pork had lower sensory texture, flavor and overall acceptability scores than the control samples, but were of acceptable quality. PMID- 22063127 TI - Effect of diet and fat content on the functional properties of thawed beef. AB - The effect of animal diet (pasture versus grain) and fat content (1, 15 and 25%) on the functional properties and quality of beef stored for 8 months at -20 degrees C was determined. After storage, pasture-finished beef had significantly (P<0.001) less malondialdehyde than grain-finished. Grain-finished beef had a more vivid red colour than pasture-finished (P<0.01). The remaining functional properties determined in this study were not affected by diet. Protein solubility, emulsion activity index, and cooked batter torsion strain decreased and hue angle increased with increasing fat content. The solubility of total and sarcoplasmic proteins and cooked batter torsion stress and strain decreased (P<0.001) and hue angle increased (P<0.001) with storage time regardless of diet and fat content. It is concluded that there is not much difference in the functional properties of beef finished on pasture or grain. However, pasture finished beef is more stable to lipid oxidation than the grain-finished, and hence may be more amenable to further processing. PMID- 22063128 TI - The influence of diets containing either conventional corn, conventional corn with choice white grease, high oil corn, or high oil high oleic corn on belly/bacon quality. AB - The objectives of this study were to evaluate diets possessing different fatty acid profiles (as influenced by corn type) with regard to fatty acid profile and firmness of pork bellies. Crossbred barrows (n=196) were fed one of four corn based diets consisting of conventional corn (CONV), CONV with choice white grease (CWG), high oil corn (HOC), or high oleic, high oil corn (HOHOC). Following 98 days on test, two animals representing the average pen weight (118 kg) were selected for harvest (n=56). A 50-g fat sample was removed from each belly for fatty acid profile analysis. Lateral and vertical flex tests were performed to determine belly firmness. Bellies were pumped and cooked according to a commercial protocol. Total saturated fatty acids increased (P<0.001) and total unsaturated fatty acids decreased (P<0.05) when CWG was added to the CONV diet or when HOC or HOHOC were substituted for CONV corn. Pigs fed CONV corn had firmer bellies, while those fed HOC were softer. No differences were observed across treatment for percentage pump retention, smokehouse yield, or slicing yield (P>0.05). Based on the results of this study, corn type influences fatty acid profile, and belly firmness, but does not affect pump retention, or slicing yields. PMID- 22063129 TI - Survey of conditioning indicators for pork loins: changes in myofibrils, proteins and peptides during postmortem conditioning of vacuum-packed pork loins for 30 days. AB - This study was performed to examine the changes in myofibrils, proteins and peptides during postmortem conditioning of vacuum-packed pork loins at 4 degrees C for 30 days. The fragmentation of myofibrils has been observed during postmortem aging for 20 days and its ratio increased until 20 days. The 32 kDa component derived from troponin T increased during storage for 20 days, while a glyceraldehyde 3-phosphate dehydrogenase (GAPDH) among sarcoplasmic proteins was significantly degraded during storage for 15 days. Some oligopeptides increased during such storage, two peptides (peptides P1 and P2) significantly increasing during storage for 20 days. Their sequences were APPPPAEVHVHEEVH (P1) and VPTPNVSVVDLT (P2). Homology analysis showed that peptides P1 and P2 were derived from troponin T and GAPDH, respectively. It was concluded that the fragmentation of myofibrils, the increases in the 32 kDa component and peptides P1 and P2, and the decrease in GAPDH were useful as conditioning indicators of progressive degree during the storage of pork loins stored at 4 degrees C. PMID- 22063130 TI - Effects of feeding elevated concentrations of monounsaturated fatty acids and vitamin E to swine on characteristics of dry cured hams. AB - Thirty Large White*Great York gilts were fed six experimental diets containing three levels of poly and monounsaturated fatty acids. Within each dietary fat treatment, one group was fed a basal level of vitamin E (20 mg alpha-tocopheryl acetate/kg diet) and the other group received a supplemented level (200 mg alpha tocopheryl acetate/kg diet). Concentration of alpha-tocopherol was significantly higher in hams from pigs fed supplemented dietary levels of vitamin E (P<0.0001), but no significant effect of dietary fat was observed. Dietary vitamin E supplementation reduced the concentration of thiobarbituric acid reactive substances after 9 days storage of sliced samples (P<0.0001), while dietary fat source showed no significant effect. Significantly lower oxidation was observed in ham homogenates from pigs fed higher concentrations of monounsaturated fatty acids after 120 min of incubation under pro-oxidant conditions (P=0.013). No effect of dietary treatment was observed in ham volatile aldehyde profile. No significant effect of dietary vitamin E was observed on surface redness during storage, but a significant effect was observed for luminosity after 7 days of storage (P=0.033). Hams from pigs fed diets enriched in monounsaturated fatty acid showed higher 'a' values (P=0.040) in stored sliced samples. Sensory evaluation revealed a significant effect of dietary vitamin E on redness of ham slices (P<0.001). Dietary supplementation with vitamin E also produced a significantly higher odour and flavour intensity (P=0.006 and P=0.01 respectively). Dry cured ham samples from pigs fed higher amounts of monounsaturated fatty acids showed a significantly higher consistency fat than those from pigs fed polyunsaturated fatty acids. PMID- 22063131 TI - Extraction properties and absorption spectra of dry cured hams made with and without nitrate. AB - The spectral and extraction properties of nitrate-free dried hams (Parma hams) were studied as a function of maturing time and muscle type (semimembranosus and biceps femoris muscles). To understand the red colour of the processed meat, a three-step extraction using water, acetone and tetrahydrofuran (THF) as solvents was employed and the extracts from each step were submitted to spectrophotometric (visible) analysis while the corresponding residues underwent instrumental (CIE L* a* b*) colour evaluation. Results showed that the drier the meat the more the pigment is soluble in organic solvents, THF proving a major extractant in matured hams, regardless of muscle type. When Parma hams were compared with hams made using nitrate, the former displayed more intense (P<0.05) absorption in the red region in the aqueous solution, lower intensities in acetone and higher values in THF solution. Major differences in spectral characteristics were found between water and organic extracts of Parma hams, with both acetone and THF solutions exhibiting a doublet at 544-584 nm, and water extracts displaying two distorted peaks at 551 and 595 nm. It is concluded that dry curing of meat without nitrate yields a lipophylic stable red pigment whose hydrophobicity increases with ageing. PMID- 22063132 TI - Patterns of growth and partitioning of fat depots in tropical fat-tailed Menz and Horro sheep breeds. AB - A total of 147 Menz and Horro lambs of both sexes were serially slaughtered and dissected at five different stages of growth to define the pattern of growth and partitioning of fat among body depots in indigenous Ethiopian Menz and Horro sheep breeds. The GLM procedure of SAS and allometric growth equation were used to assess the effects of various factors on the growth of body depots and to estimate its growth relative to total carcass fat (TCF) and empty body weight (EBW), respectively. Results obtained showed that the growth of carcass fat (CF), non-carcass fat (NCF) and tail fat (TF) is significantly affected by the genotype (P<0.001) and stages of growth (P<0.001) of lambs. Except for CF, the growth of both NCF and TF were also significantly affected (P<0.001 and P<0.05) by the sex and the season in which the lambs were born. Of the two breeds, the Menz sheep deposited more fat into the carcass and less into the non-carcass depots as compared to the Horro sheep and ewe lambs in both breeds deposited more fat intra abdominally than the ram lambs. The highest allometric growth coefficient was obtained for TF (1.2-2.1 relatively to TCF and EBW) and the lowest for NCF (0.8 1.3 relative to TCF and EBW) indicating that the former is a late developing while the later is an early maturing depot in the tropical fat-tailed Menz and Horro sheep breeds. PMID- 22063133 TI - Physico-chemical characteristics of M. Longissimus dorsi from three lines of free range reared Iberian pigs slaughtered at 90 kg live-weight and commercial pigs: a comparative study. AB - Longissimus dorsi muscles from three lines of Iberian pig and those from commercial pigs were analysed in order to evaluate their quality for fresh consumption. Iberian pigs were reared in a natural outdoor production system with access to grass, while m. Longissimus dorsi from commercial pigs were procured from a local slaughterhouse. Iberian pigs' Longissimus dorsi showed a higher fat (P<0.05) and lower phospholipid contents (g PL/g fat; P<0.05) than Longissimus dorsi from commercial pigs. Iberian pigs' Longissimus dorsi muscles had a higher content of haem iron (P<0.05) than those from commercial pigs and consequently m. Longissimus dorsi exhibited a redder colour (higher a*-value) that diverged less from the true red axis (lower hue value; P<0.05) than those from commercial pigs which resulted paler (higher L*-value; P<0.05). Total fat and neutral lipid fatty acid profiles showed higher percentages of palmitic, oleic, total saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) m. Longissimus dorsi of Iberian pigs than in the commercial ones (P<0.05). m. Longissimus dorsi from the commercial pigs contained higher proportions of polyunsaturated fatty acids and a higher n-6/n-3 ratio value (P<0.05). PMID- 22063134 TI - Warner-Bratzler shear evaluations of 40 bovine muscles. AB - Forty muscles from each of 20 beef carcass sides were used to perform Warner Bratzler shear (WBS) force determinations for within and among muscle effects. The M. triceps brachii differed (P <0.05) in WBS values between the caput longum and caput laterale, and the M. gluteobiceps differed (P <0.05) in WBS values between the vertebral, cranial, and caudal portions. The M. trapezius did not differ between the pars cervicalis and pars thoracica. Larger muscles were evaluated for location effects within muscles. The M. pectoralis profundus, M. infraspinatus, M. triceps brachii (caput longum), psoas major, and M. semimembranosus all had significant location effects. Muscles were allocated into "very tender," "tender," "intermediate" or "tough" categories. Those muscles considered "very tender" (WBS <3.2 kg) were the diaphragm (outside skirt or wing of diaphragm), M. spinalis, M. infraspinatus, M. iliacus, M. psoas major, M. serratus ventralis, M. biceps brachii, M. obliquus internus abdominis, and M. vastus medius. Muscles considered "tender" (3.2 kg 4.6 kg) were the M. extensor carpi radialis, M. trapezius, M. brachialis, M. pectoralis profundus, and M. flexor digitorum superficialis (hind limb). The diaphragm muscle was the most tender (WBS=2.03 kg), and the M. flexor digitorum superficialis was the toughest (WBS=7.74 kg). Tenderness, as measured by WBS, varied among and within bovine muscles, and knowledge of this variation allows for more appropriate use for specific purposes in the marketplace. PMID- 22063136 TI - A survey of the dielectric properties of meats and ingredients used in meat product manufacture. AB - The objective of the present study was to improve understanding of interactions between microwave (MW) and radio frequency (RF) radiation and meat/meat products. Dielectric properties at 27.12, 915 and 2450 MHz of lean, fat, aqueous solutions/suspensions and meat blends of typical ingredients used in meat product manufacture were measured. In addition temperature rises of ingredient/meat blends were compared following RF or MW heating. Frequency affected dielectric properties as did composition, with fat having lower dielectric activity than lean. Dielectric properties at MW frequencies appeared more sensitive to composition changes. Ingredients could be subdivided into groups having either lower or higher dielectric activity than lean, with concentration influencing which group an ingredient fell into. When low and high dielectric activity ingredients were incorporated into lean meats dielectric properties did not correlate well with temperature rises indicating the importance of other factors in addition to dielectric properties in determining temperature rise. PMID- 22063137 TI - Simulation of the distribution of current density in the brain of slaughter pigs with the finite element method. AB - The current density in the brain of a slaughter pig during electric stunning was calculated and visualised with an finite element method computer model. The anatomic model of the pig's head was constructed with the computer programme Ansys. Ansys offers the possibility of calculating the current density between electrodes in any position using the mathematical "finite element method" model. After calculation the current density distribution can be visualised in planes in any direction through the pig's head. Our simulation confirmed the common practice of positioning the electrodes for electric stunning either eye to eye or eye to ear, because the highest current density through the brain was calculated for these positions. Setting the electrodes further caudally reduced the current density remarkably and, stunning is therefore not guaranteed. Additionally, this model showed for the first time that, due to their lower resistance, the nervus opticus and blood vessels conduct the current like wires into the brain. PMID- 22063138 TI - Colour and lipid oxidation changes in dry-cured loins from free-range reared and intensively reared pigs as affected by ionizing radiation dose level. AB - The effect of irradiation (0, 5 and 10 kGy) of vacuum-packaged Iberian dry-cured loin slices from pigs fed on concentrate (CON) or free-range reared (FRG) was studied in relation to colour changes, TBA-RS and hexanal content. Both, ionizing radiation and type of loin had a significant effect on the instrumental colour parameters of the samples. Irradiation resulted in significantly higher a*-values in both sets of loins, indicating a redder colour. Numerically calculated total colour difference (DeltaE) changes were significantly less intense in CON vacuum packaged dry-cured loin slices than in FRG samples and changed significantly at 10 kGy dose levels in both types of samples. TBA-RS numbers were significantly affected by irradiation dose and type of loin and increased linearly with dose in both types of slices. Increments in TBA-RS numbers in FRG loin slices was dose dependent and was closely related to the type of dry-cured loin. Irradiation of dry-cured loin slices significantly increased hexanal contents in both groups of loins and the increases were dose-dependent and greater in FRG samples than in CON samples. Differences in the characteristics of the raw material and initial lipid oxidation level could play an important role in the irradiation-induced changes in vacuum-packaged dry-cured loin slices. PMID- 22063139 TI - Selection of muscles as indicators of tenderness after seven days of ageing. AB - The selection of a muscle that could be used as an index muscle for beef tenderness was performed using nine commercially important muscles. A total of 50 bulls, Charolais*Alentejano (n=9), Simmental*Alentejano (n=9) and Alentejano (n=32), were slaughtered at two different commercial live weights: crossbred animals (sample A) between 500 and 600 kg (carcass weight between 310 and 370 kg) and purebred Alentejano (sample B) between 350 and 450 kg (carcass weight between 185 and 295 kg). Slaughter ages varied between 16 and 24 months in both groups. The shear force of nine muscles (Mm. biceps femoris, gastrocnemius, longissimus thoracis, longissimus lumborum, quadriceps femoris, semimembranosus, semitendinosus, supraspinatus and triceps brachii caput longum) was assessed seven days post-mortem. In both samples, the comparison between different muscle means and the combined mean of all muscles and the respective correlations showed that the Mm. biceps femoris and semimembranosus could be used as index muscles. However, the biceps femoris is preferred, because it showed greater stability in terms of the coefficient of variation. PMID- 22063140 TI - Sensory based quality control utilising an electronic nose and GC-MS analyses to predict end-product quality from raw materials. AB - The objective of the present study was to investigate if an electronic nose, comprising six metal oxide sensors (MOS) could predict the sensory quality of porcine meat loaf, based on measuring the volatiles in either the raw materials or the meat loaf produced from those raw materials. A multivariate data analysis strategy involving analysis of variance partial least squares regression (APLSR) and principal component analysis (PCA) was used to determine causal and predictive relationships between the raw material and meat loaf samples, sensory analysis, electronic nose, and GC-MS measurements. The results showed that the six MOS sensors in the Danish odour sensor system (DOSS) could detect the raw materials that led to unacceptable products, as determined by sensory profiling and in-house sensory quality control (QC), and separate those raw materials from each other, based on the volatile composition, as determined by GC-MS. However, the electronic nose was unable to detect all the sensory unacceptable meat loaf samples themselves due to changes in the volatile composition after cooking. Analysis of the GC-MS compounds identified from raw materials and meat loaf samples indicate that two MOS sensors mainly responded to alcohols and to a lesser degree to aldehydes and alkanes, whereas two other sensors most likely responded to low molecular weight sulphur compounds. Thus, the results indicate that measuring volatiles with the MOS sensors in the DOSS system, on raw materials for processed meat products, may be a feasible strategy in sensory based quality control, and may also have potential in predicting the sensory quality of the end product. PMID- 22063141 TI - Characterization of French and Spanish dry-cured hams: influence of the volatiles from the muscles and the subcutaneous fat quantified by SPME-GC. AB - The influence of the volatile compounds on the characterization of Spanish and French dry-cured hams was studied. Thirty volatiles were quantified in each one of four locations (biceps femoris, semimembranosus and semitendinosus muscles and subcutaneous fat) of 29 dry-cured hams by solid-phase microextraction gas chromatography (SPME-GC). The Brown-Forsythe univariate test allowed determination of the volatiles that individually could characterize (p<0.05) the samples by their geographical origin (France, Spain) and breed type (Iberian, white). Stepwise linear discriminant procedure, under very strict conditions (F to-Enter for a F-distribution>0.95), then selected the most remarkable volatile compounds. Four compounds from the subcutaneous fat (methyl benzene and octanol) and the semitendinosus muscle (2-butanone and 2-octanone) allowed 100% correct classifications by geographic origin. On the other hand, only two compounds from the subcutaneous fat (octanol) and the biceps femoris muscle (3-methyl 1-butanol) correctly classified all the samples by the breed type. The ability of these variables to classify the samples was checked by the unsupervised procedure of principal components. PMID- 22063142 TI - The effect of feed withdrawal during lairage on meat quality characteristics in ostriches. AB - Commercially reared ostriches (n=84) were randomly allocated to one of two groups. The first group (stressed: n=38) was deprived of food for a period of 2.5 days prior to slaughter, to simulate the stress experienced by slaughter ostriches held in holding pens (lairage) at a commercial ostrich abattoir over a weekend. The second group (control: n=46) was fed normally until 24 h prior to slaughter. Initial live weight as well as hot and cold drumstick weight were independent (P>0.05) of treatment. Stressed birds lost on average (+/-SE) approximately three times more weight than control birds over the experimental period (-3.2+/-0.6 vs. -1.0+/-0.5 kg, respectively). Full stomach and alimentary tract weights did not differ between treatments although there was a tendency for that derived from stressed birds to have lower stomach contents. The intra muscular (Muscularis iliofibularis) pH(f) of stressed birds was 0.22 units higher (P<0.01) than that of contemporaries in the control group 1 h post-slaughter (6.03+/-0.06 vs. 5.81+/-0.05, respectively). After 26.5 h in a refrigerated room, this difference still remained at 0.25 units (6.46+/-0.07 vs. 6.21+/-0.07, respectively; P<0.05). Post-slaughter changes in intra-muscular pH followed approximately the same trend in stressed and control birds. Intra-muscular temperature was largely independent of treatment, although there was a suggestion of a slightly higher (P=0.18) temperature in stressed birds immediately post slaughter. Cooking loss, drip loss and shearing values were not affected (P>0.05) by the withholding of food for 2.5 days. It can thus be concluded that withholding feed from ostriches on lairage over a period of 2.5 days does not have any negative influence on the meat yield or physical quality traits thereof. PMID- 22063143 TI - Purification and identification of angiotensin converting enzyme inhibitory peptides from beef hydrolysates. AB - Sarcoplasmic protein extracts from beef rump (biceps femoris) were hydrolyzed (for 0, 4, 8, 12, and 24 h) with three enzymes or their paired combinations. Ultrafiltration, gel-filtration, and RP-HPLC were used to separate angiotensin converting enzyme (ACE) inhibitory peptides from the hydrolysates. The highest ACE inhibitory activity of enzyme hydrolysates resulted from 4 h incubation with enzymes or their paired combinations. The activities of gel filtrated fractions from these hydrolysates were assayed in vitro, demonstrating that the 3rd peak of enzyme thermolysin+proteinase A hydrolysate had the highest ACE inhibition activity (52.8%). The 3rd peak of this hydrolysate was separated by RP-HPLC into five peaks, of which peak 3 showed 30.1% ACE inhibition activity. Its peptide sequence was determined to be Val-Leu-Ala-Gln-Tyr-Lys. The results suggested that this peptide may be a potent ACE inhibitor which might perhaps be used to develop beef with a bioactive peptide to lower blood pressure. PMID- 22063144 TI - (23)Na-MRI quantification of sodium and water mobility in pork during brine curing. AB - A model study on movements of sodium ions in pork loin during brining was carried out using (23)Na-magnetic resonance imaging ((23)Na-MRI). Samples of different pH and post-mortem age were mounted in Plexiglas((r)) cylinders with built-in phantoms and cured in 18.9% and 18.1% NaCl (w/v), respectively. One-dimensional (23)Na-MRI and apparent diffusion coefficient (ADC) profiles were obtained over 5 days with intervals of 24 h. On day 5 the meat was cut into 1 cm slices and analyzed for chloride content. (23)Na-MRI and ADC profiles of meat provided detailed non-destructive information about salt and water movements during brine curing. Quantification of salt concentration in meat by one-dimensional (23)Na MRI profiling proved successful at values above 0.9 g NaCl/100 g sample in the meat. (23)Na measurements were calibrated against chemically determined chloride, yielding a linear relationship. (23)Na-MRI profiles suggested that the diffusion of salt into whole meat cuts cannot be described by simple ordinary Fickian diffusion with a constant diffusion coefficient. The diffusion coefficient is suggested to be affected by changes in NaCl concentration, swelling and degree of dehydration. PMID- 22063145 TI - Colour changes after carcasses decontamination by steam and lactic acid. AB - The surface decontamination of meat by steaming and by lactic acid prolongs its shelf life. Possible changes of colour were evaluated by reflectance spectrophotometry and video image analysis (VIA). Reflectance spectra were measured using a D(65) source and CIELab values L(*), a(*) and b(*) were calculated together with ratios of the different myoglobin forms (red, oxy, met). The same samples were evaluated by video image analysis (software LUCIA). Steaming and spraying with lactic acid increased slightly the lightness (L(*)) of the meat surface. Coordinate a(*) (redness) decreased slightly after the decontamination treatment. This was confirmed by VIA; brightness increased and red-ratio r decreased. Both methods, i.e. reflectance spectrophotometry and VIA, reflect the colour changes in a similar way. The main advantage of reflectance spectrophotometry was its higher sensitivity and the possibility of direct calculation of the ratio of the haem pigment forms. However, video image analysis allows analysing of different particles in the image and this method is therefore a suitable tool for monitoring the changes of the surface appearance. PMID- 22063146 TI - Chemical, physical and sensory properties of meat from pure and crossbred Podolian bulls at different ageing times. AB - The present study aimed to investigate the effect of crossbreeding with Limousine sires on fatty acid profile, physical and sensory properties of meat produced by Podolian young bulls. Polyunsaturated fatty acid content was influenced by crossbreeding (P<0.01) with Podolian bulls (P) producing beef characterised by a higher level of unsaturation in comparison with crossbred animals (LP). As a consequence, P/S ratio was significantly higher in meat produced by P animals than LP (P<0.01). P animals had higher linoleic (P<0.05), linolenic (P<0.05), EPA (P<0.05) and DHA acids (P<0.001) levels than LP subjects. No breed effect was observed for the ratio n-6/n-3 (P>0.05). WBS force of LD was significantly lower in meat from crossbred subjects (P<0.05). Both crossbreeding with Limousine and extension of ageing from 2 to 7 days improved LD tenderness as assessed by panel taste (P<0.001). PMID- 22063147 TI - The effect of growth rate during backgrounding and finishing on meat quality traits in beef cattle. AB - The relationship between growth rate and meat tenderness was investigated in ~7000 cattle from temperate and tropically adapted breeds, finished on either pasture or in a feedlot to one of three market weights. Growth rate was calculated from weaning to the beginning of finishing (backgrounding) and over the finishing period, for both contemporary groups and individuals within these groups. Shear force and compression of longissimus lumborum (striploin) and semitendinosus (eye round) were measured at two days ageing, and palatability of the striploin at 14 days ageing. Analyses assessed the importance of growth rate during backgrounding and finishing on both a within group and between group basis. Where significant in individual animals, increased growth rate resulted in more palatable or tender meat, but the results were not consistent between breed types, locations, or the two muscles sampled. The most consistent relationship was an increase in palatability of the striploin with increased growth rate during finishing. Increased growth rate of groups during backgrounding improved palatability consistently across breedtypes, finish and location, however most of this relationship was accounted for by difference in mean group age at slaughter. PMID- 22063148 TI - Stress hormones, carcass composition and meat quality in Large White*Duroc pigs. AB - The levels of stress hormones, cortisol and catecholamines (adrenaline and noradrenaline), were measured in urine collected after slaughter from the bladder, in 309 pigs (females and castrated males) from an F2 intercross between the Large White and Duroc breeds to analyze the relationships between stress responsive neuroendocrine systems, carcass composition and meat quality. Intramuscular fat content was measured from a biopsy sample taken at a live weight of 70 kg from the longissimus lumborum muscle, and carcass and meat quality traits were also collected. Carcass fat content was higher and estimated carcass lean meat content was lower with increasing urinary levels of cortisol and adrenaline (that are highly correlated with each other), but was not related to the levels of noradrenaline, showing that adrenal hormones favor the accretion of fat at the expense of muscle proteins, a typical physiological effect of cortisol. On the contrary, intramuscular fat levels were unrelated to either hormone level. Finally, muscle pH measured 24 h after death was positively correlated with catecholamine levels, an effect related to the catabolism of muscle glycogen by catecholamines released by preslaughter stress, which impairs post-mortem acidification of meat. These results show the importance of a control over stress neuroendocrine systems to increase pork production and product quality, and the value of the genetic approach to reach this goal. PMID- 22063149 TI - Relationships between sensory perception and water distribution determined by low field NMR T(2) relaxation in processed pork - impact of tumbling and RN(-) allele. AB - The relationships between water distribution, measured with low-field NMR (LF NMR) transverse (T(2)) relaxometry and sensory properties in tumbled and non tumbled cured-smoked loins from 30 female Hampshire crossbred pigs were investigated. Upon distributed analysis of the T(2) relaxation, three populations centred at about 2, 40 and 600-800 ms, respectively, were detected. Clear differences in the characteristics of the intermediate population (T(21)) were observed between loins from carriers and non-carriers of the RN(-) allele, which implies differences in water-protein interactions between the two genotypes. PLS regressions between NMR T(2) variables and sensory attributes revealed significant correlations between NMR T(2) variables and the sensory attributes juiciness, acidulous taste and meat taste, which mainly could be ascribed to the T(21) time constant. In addition, the number of unappealing pores assessed by the sensory panel was highly related to the relative T(2) populations, implying that the microstructure is directly reflected in the NMR T(2) populations. However, prediction of the processing yield from NMR T(2) variables was poor. The correlation improved when RN genotypes and tumbling conditions were included as predictors. Thus, other effects of tumbling treatments and RN genotypes unrelated to NMR T(2) relaxation were observed. PMID- 22063150 TI - Effect of tumbling and RN genotype on sensory perception of cured-smoked pork loin. AB - Effects of tumbling and RN genotype on sensory perception of cured-smoked loins were studied on loins from 32 crossbred female pigs containing Hampshire blood. Right-side loins were intermittently tumbled during 4 h, whereas left-side loins were left non-tumbled. Tumbled loins were more tender and uniform in cured colour as well as less acidulous in taste compared with non-tumbled loins. Further, the formation of undesirable pores was lower in tumbled loins. Final juiciness tended to be higher and meat taste intensity lower in tumbled loins, whereas initial juiciness did not differ. There were no significant interactions between tumbling and RN genotype for sensory attributes. RN(-) carriers (RN(-)/rn(+)) were more acidulous in taste, had more pronounced meat taste and were saltier than non carriers (rn(+) /rn(+)). Moreover, they tended to have higher initial juiciness and more undesirable pores, and be less homogeneous in cured pink colour. No differences in consumer preference between the four treatments were detected in the ranking test, but most persons ranked non-tumbled loins highest regarding overall liking. Instrumental tenderness measurements agreed well with sensory tenderness scores. PMID- 22063151 TI - Evolution and identification of lactic acid bacteria isolated during the ripening of Sardinian sausages. AB - Lactic acid bacteria (LAB) were isolated during the production and the ripening of Sardinian sausage, a typical Italian dry fermented sausage. Samples were taken at different stages, and 112 strains were isolated. The isolates were characterized using the micromethod proposed by Font de Valdez et al. [Font de Valdez, G., Savoy de Giori, G., Oliver, G., & De Ruiz Holgado, A. P. (1993). Development and optimization of an expensive microsystem for the biochemical characterization of lactobacilli. Microbiologie Aliments Nutrition, 11, 215-219]. Schillinger and Lucke's [Schillinger, U., & Lucke, F. K. (1987). Identification of lactobacilli from meat and meat products. Food Microbiology. (4), 199-208] scheme and the biochemical patterns given by Bergey's Manual of Systematic Bacteriology [Bergey's Manual of Systematic Bacteriology (1986). Baltimore: William and Wilkins] were used for preliminary identification. A PCR-based method was then used to confirm the results. LAB were the dominant flora during ripening. They consisted mainly of homofermentative mesophilic rods. Lactobacillus sakei (43,3%), Lactobacillus plantarum (16,6%) and Lactobacillus curvatus (13,3%) were the main isolates. The results of the biochemical identification methods agreed well with those of PCR-based identification (91% agreement). PMID- 22063152 TI - The antioxidant properties of baechu-kimchi and freeze-dried kimchi-powder in fermented sausages. AB - The antioxidant properties of baechu-kimchi in fermented sausages were evaluated by investigating its effect on the changes in total free fatty acid content, peroxide value, and TBARS during ripening. The conditions for its antioxidant effectiveness were optimized in a model system (beaker sausages). For this, the conditions of added kimchi - form (kimchi and freeze-dried kimchi-powder), fermentation temperature (7 and 20 degrees C) and concentrations (5%, 10% and 15%) - were varied. The results were compared with that of the control without kimchi. According to the evolution of peroxide value and TBARS, the addition of 5% and 10% kimchi clearly indicated retardation of the development of lipid oxidation. However, an increase in the amount of kimchi added caused a prooxidant effect. The antioxidant effect of kimchi has been found to be dependant on its fermentation temperature as the batches treated with kimchi fermented at 20 degrees C displayed better protection against the formation of oxidative products than those fermented at 7 degrees C. Kimchi-powder did not show any antioxidant properties. PMID- 22063153 TI - The effect of different convection cooking methods on the instrumental quality and yield of pork Longissimus dorsi. AB - The effect of different cooking methods (natural convection, NC, forced convection, FC and forced convection/steam combined, FC/S) on selected physical properties of cooked pork Longissimus dorsi samples were compared. FC/S treatment was significantly faster (~19 min) than NC and FC cooking treatments (~27 min). The overall cook values at the center of all samples (calculated taking into consideration the cooling phase) were comparable and might explain the similar tenderness found among samples that underwent significantly different thermal histories. The weight loss of the FC/S samples was significantly higher than in the other cooking methods while the color of the surface was paler than the NC and FC ones. PMID- 22063154 TI - Fatty acid composition and carcass characteristics of growing lambs fed diets containing palm oil supplements. AB - Thirty 45-day-old male Ojalada lambs were used to investigate the effect of palm oil (as such or in the form of calcium soap) on carcass characteristics and fat composition. Dietary palm oil did not significantly affect dorsal fat thickness, carcass fatness or carcass conformation. The palm oil supplement did not affect C16:0 levels in intramuscular and subcutaneous fat, but did increase the percentage of C16:0 and reduce PUFA and MUFA content in internal fat depots. Supplementation with palm oil in the form of calcium soap did not cause significant differences in the composition of intramuscular fat. Subcutaneous and perirenal fat of lambs fed treatments including palm oil as such contained higher levels of some saturated fatty acids than that of those fed fat in the form of calcium soap. Mesenteric fat of lambs that received calcium soap had less % C18:1 and more % C18:3 than that of those given palm oil. PMID- 22063155 TI - Functional stability of frozen normal and high pH beef. AB - The functional properties of whole, diced or minced high and normal pH beef were determined after 0, 1, 2, 3 and 7 month's storage. There was no interaction between pH, degree of comminution and storage time for most of the attributes measured. Regardless of storage time or comminution method, high pH meat had significantly (P<0.001) higher sarcoplasmic protein solubility, water holding capacity, cooked batter torsion stress and strain, yield and emulsion stability than normal pH meat. Normal pH meat had significantly (P<0.01) higher myofibrillar protein solubility and hue angle than high pH meat. Water holding capacity significantly (P<0.01) decreased and hue angle increased with the increase in the degree of comminution. Protein solubility in raw meat and the cooked batter stress, strain, yield and emulsion stability of both high and normal pH meat deteriorated with time. However, this deterioration was faster in the normal pH meat compared to high pH meat except for total and myofibrillar protein solubility. Within the parameters of the present study, it is concluded that frozen high pH meat possesses superior functional attributes compared to normal pH meat regardless of the degree of comminution or storage time. PMID- 22063156 TI - Addition of tea catechins and vitamin C on sensory evaluation, colour and lipid stability during chilled storage in cooked or raw beef and chicken patties. AB - The effects of addition of tea catechins (TC) and vitamin C (VC) on sensory evaluation, colour and lipid stability in cooked or raw beef and chicken meat patties during refrigerated storage were studied. Fresh beef striploin and chicken breast muscles were minced, following removal of external fat and connective tissue. Following mincing, beef and chicken were assigned to one of the following five treatments: control (meat treated with no antioxidant); TC200, meat plus 200 mg TC/kg muscle; TC400, meat plus 400 mg TC/kg muscle; VC200, meat plus 200 mg VC/kg muscle, VC400, meat plus 400 mg VC/kg muscle. Sodium chloride (1%) was added to all samples. Patties (125 g portions), formed from the above treated minced meat, were oven cooked, cooled, and packaged in 30% CO(2):70% N(2). Fresh raw beef and chicken patties were packaged in 80% O(2):20% CO(2). All samples were stored for up to 7 days under fluorescent lighting at 4 degrees C. Sensory parameters (colour, flavour, taste, tenderness and overall acceptability) were evaluated on cooked beef and chicken patties after 1, 3 and 6 days of storage. Surface colour (Hunter L, a and b values), and lipid oxidation (2 thiobarbituric acid reactive substances) were measured on days 1, 3 and 6 of storage for cooked meats and on days 2 and 7 for raw beef and chicken. Tea catechins addition (200 or 400 mg/kg) to minced meat caused (P<0.05) discolouration in cooked beef and chicken meat patties and significantly reduced (P<0.001) lipid oxidation in cooked or raw beef patties compared to the control. Beef, either raw or cooked, was more susceptible (P<0.01) to oxidation compared to chicken. Raw meat stored in high oxygen conditions was more susceptible to lipid oxidation than cooked meat stored in anaerobic conditions. Tea catechins treatments (TC200 and TC400) inhibited (P<0.05) lipid oxidation in raw beef to a greater extent than vitamin C treatments (VC200 and VC400). These results indicate that tea catechins are potent natural antioxidants and exhibit greater antioxidant efficacy compared to vitamin C. PMID- 22063157 TI - Physicochemical properties of low sodium frankfurter with added walnut: effect of transglutaminase combined with caseinate, KCl and dietary fibre as salt replacers. AB - This study compares the effects of combinations of microbial transglutaminase (TGase) and various non-meat ingredients (caseinate, KCl and wheat fibre) used as salt replacers, with the effects of NaCl on the physicochemical properties (cooking loss, emulsion stability, texture and colour) of frankfurters with added walnuts. The combination of TGase with caseinate, KCl or fibre led to harder, springier and chewier (P<0.05) frankfurters with better water- and fat-binding properties (emulsion stability and cooking loss) (P<0.05) than those made with TGase only. Ranking of ingredient efficiency in combination with TGase showed that caseinate>KCl>fibre. Frankfurters with caseinate presented the highest lightness and the lowest redness values. Frankfurter with NaCl had a harder, springier and chewier gel/emulsion network with lower cooking loss than those NaCl free. PMID- 22063158 TI - Factors affecting acceptability of dry-cured ham throughout extended maturation under "bodega" conditions. AB - The evolution of biochemical, instrumental colour and texture, sensory parameters and consumer acceptability of 12-month dry-cured hams maintained up to 26 months under "bodega" conditions (18 degrees C, 75% relative humidity) was assessed, in order to investigate the influence of extended ripening on their sensory characteristics and acceptability. Results demonstrated that ham acceptability showed no significant differences (p>0.05) from 12 to 22 months, while it decreased significantly (p<0.05) until 26 months. Principal component analysis of all data brought about a comprehensive explanation of the biochemical, instrumental and sensory parameters involved in the acceptability decrease. In fact, high pastiness and adhesiveness values, as measured by both sensory and instrumental methods, appeared to be most related to decreasing acceptability. Those attributes were the result of an excessive proteolysis, as revealed by biochemical maturation indices. PMID- 22063159 TI - Breed, slaughter weight and ageing time effects on consumer appraisal of three muscles of lamb. AB - Consumers (n=265) tasted semitendinosus (ST), semimembranosus (SM) and gluteo biceps (GB) (right and left) from 180 entire male lambs. Muscles were from three Spanish breeds: Rasa Aragonesa (local meat breed), Churra (local dairy breed) and Spanish Merino. Within breed, three slaughter live weights were considered (10 12, 20-22 or 30-32 kg). Isolated muscles were aged under vacuum package for 1, 2, 4, 8 or 16 days. Consumers evaluated tenderness, flavour quality and overall acceptability. Globally, the three attributes were significantly influenced by breed, slaughter live weight and ageing. Considering breed effect, Churra had the lowest scores for tenderness in the heaviest lambs while Spanish Merino was the most tender at 20-22 kg but there were no differences between either for 10-12 kg lambs. Muscles from the heaviest lambs were considered the toughest and those from the 10-12 kg lambs the most tender. Tenderness improved with ageing, but more for SM and GB. Flavour was better in the lightest lambs and, in general, it was not affected negatively by ageing. Consumers preferred meat from the 10-12 kg lambs in all breeds (the most tender and with the best flavour) and aged for intermediate to long periods (4-16 days). For the three attributes, the ST muscle had the best ratings at short ageing times and GB at long ageing times. PMID- 22063160 TI - A note on the incidence and antibiotic resistance of Staphylococcus aureus isolated from meat and chicken samples. AB - One hundred and fifty samples of raw calf/lamb meat samples (mince and chunks) and chicken parts (giblets, carcass) were analysed for the presence of Staphylococcus aureus. Eighty S. aureus strains were isolated and identified. Resistance of the strains to methicillin and other antibiotics was determined by the Kirby-Bauer disc diffusion test. The overall methicillin resistance rate for S. aureus was 67.5%. Of S. aureus strains, 87.5% were resistant to bacitracin. A high prevalence of penicillin G resistance was detected for S. aureus (53.8%). Few of the strains were resistant to erythromycin (7.5%). All strains were susceptible to vancomycin, sulbactam-ampicillin, ciprofloxacin and cefaperazone sulbactam. This study confirmed the presence of S. aureus, especially antibiotic resistant strains, in the foods examined, indicating poor sanitary conditions during processing which may create a health risk for consumers. PMID- 22063161 TI - Microbiological condition of beef mechanically tenderized at a packing plant. AB - When striploins were mechanically tenderized at a beef packing plant, the log total numbers of aerobes, coliforms, staphylococci/listerias and Escherichia coli recovered from surfaces before or after tenderizing were about 2.8, 2.0, 0.6 and 0.3 log cfu 25 cm(-2), respectively. The numbers of those organisms recovered from the deep tissues of the tenderized meat were about 2.0, 1.5 and 1.2 log cfu 25 g(-1) and none, respectively. The aerobes recovered from the deep tissues were unexpectedly numerous in view of the small numbers of bacteria on meat surfaces. That suggests deep tissue contamination was affected by factors other than the numbers on meat surfaces. After cooking tenderized beef to medium rare or well done conditions, with maximum temperatures at steak centres of ?65.4 or ?73.4 degrees C, respectively, aerobes were recovered from only 2 of 25 samples cooked to each condition, at numbers of one or two per sample. This indicates that such cooking can ensure the microbiological safety of mechanically tenderized beef prepared under controlled conditions. PMID- 22063162 TI - Influence of resveratrol on oxidative damage in genomic DNA and apoptosis induced by cisplatin. AB - Cisplatin is a potent chemotherapeutic agent that has gained widespread use against various malignant tumours in a variety of human malignancies. Like other chemotherapeutic agents, cisplatin is genotoxic and apoptogenic in non-tumour cells and the formation of reactive oxygen species appears to be responsible for these toxicities. The anti-genotoxic and anti-apoptotic effects of resveratrol, a polyphenol found in numerous plant species, against cisplatin-induced genotoxicity and apoptosis in vivo were evaluated by use of standard techniques in somatic and germinal cells of mice. Pre-treatment of mice with resveratrol significantly reduced cisplatin-induced genotoxicity and apoptosis and effectively suppressed the apoptotic signalling triggered by cisplatin. The protective effect of resveratrol was found to be stronger at the higher dose, indicating the dose-dependent effect of resveratrol. Cisplatin induced marked biochemical alterations characteristic of oxidative DNA stress. Prior administration of resveratrol before the cisplatin challenge ameliorated these biochemical markers. In conclusion, this study provides evidence for the first time that resveratrol has a protective role in the abatement of cisplatin-induced genotoxicity and apoptosis in somatic and germinal cells of mice. This activity resides, at least in part, in its radical scavenger activity. Therefore, resveratrol can be a promising chemoprotective agent to avert secondary malignancies and abnormal reproductive outcomes in cured cancer patients exposed to cisplatin, without diminishing its anti-neoplastic activity. PMID- 22063163 TI - International Congress of Meat Science and Technology - ICoMST 2008. PMID- 22063164 TI - Animal welfare at markets and during transport and slaughter. AB - This review highlights some recent developments in our understanding of stress and physical injuries that occur before and during transport to slaughter, during handling at livestock markets, and at the time animals are put-up for slaughter within abattoirs. Stress in pigs during transfer to the stunning point within the abattoir has important effects on meat quality, and there is growing evidence that strenuous exercise or CO(2) stunning can contribute to oxidative rancidity in pigs, poultry and fish. In the EU, putting cattle through a crush in order to check that their eartag numbers correspond to their passport numbers is imposing additional stress, and there are reports that it is leading to greater hide contamination with Escherichia coli O157. Recent developments in stunning and slaughter include a better understanding of the causes of variation in captive bolt gun performance, the effectiveness of poll instead of frontal shooting in water buffalo, the prevalence of false aneurysms in carotid arteries during shechita and halal slaughter, and the stress effects of CO(2) stunning in fish. Stunning pigs with 90% CO(2) leads to less PSE meat than 80% CO(2). There have been concerns about the physical activity that cattle show following electrical stunning with an electrically induced cardiac arrest, and with electrical stunning using DC waveforms in broiler chickens. There is also growing concern about the hygiene problems that exist in wet markets, where animals are slaughtered alongside meat that is on display to customers. PMID- 22063165 TI - Have we underestimated the impact of pre-slaughter stress on meat quality in ruminants? AB - Stress is the inevitable consequence of the process of transferring animals from farm to slaughter. The effects of chronic stress on muscle glycogen depletion and the consequent dark cutting condition have been well documented. However, there has been little examination of the consequences of acute stress immediately pre slaughter on ruminant meat quality. New evidence is emerging to show that non pH mediated effects on meat quality can occur through pre-slaughter stress in cattle and sheep. This paper reviews the general aspects of pre-slaughter stress in the pre-slaughter context. It then examines the impacts of pre-slaughter stressors on ruminant carcass and meat quality and considers remedial strategies for remediating and preventing pre-slaughter stress. Further quantification of the biological costs of pre-slaughter stress and the consequences to meat quality is required. PMID- 22063166 TI - Changes in the nutrient quality of meat in an obesity context. AB - Today, being either overweight or obese is becoming the norm both in developing and developed countries. Developing countries often experience a double burden of nutrition-related diseases, as both over and undernutrition are experienced, with overweight presently exceeding underweight in most developing countries. Global diet trends such as moving from a traditional diet to more refined foods and increased sugar and saturated fat intake are identified as contributing to excess energy intake. The nutritional content of meat is non-homogenous and dynamic and meat has changed considerably in fat content, in many countries, during the last decade due to consumer demand. Choosing a particular meat cut of a specific fatness level, prior to cooking and consuming it without added high energy condiments, as well as trimming on the plate, can make a significant contribution to decrease energy intake, from a total diet perspective. Prudent portion size is also of importance. Meat is recognised as an important source of protein, vitamin B(12), Vitamin D and essential Omega 3 fatty acids, as well as bio-available minerals such as iron, zinc and selenium. PMID- 22063167 TI - The animal fat paradox and meat quality. AB - The purpose of this paper is to address some of the paradoxical issues and perceptions regarding animal fats and the related effects on meat quality and consumer perceptions. Meat scientists have been studying carcass characteristics for many years and although the factors that influence the accumulation, distribution and composition of carcass fat in livestock have been extensively researched, the role, value and perceptions of animal fats in meat quality differ significantly in importance between producers, abattoirs, butchers, retailers and consumers. Fat and long-chain fatty acids, whether in adipose tissue or muscle, contribute to important aspects of meat quality and are central to the nutritional and sensory values of meat. In this review the nutritional value of fat, as well as the importance of fat in terms of carcass and meat quality will be highlighted. The 'quality' of meat depends greatly on the socio-demographic backgrounds of the consumer. The aim is to focus on the global importance of fat in the carcass to the producer, processor and consumer. There is currently no clear cut definition for fat quality because the acceptability and perceived quality of fat varies significantly in terms of quantity, colour, consistency and chemical composition in different species of livestock around the world. The association between animal fats and human health is critical and recommendations by health professionals range from excluding fats altogether to a moderate consumption of fats due to their essential role in the body. Recently the emphasis has shifted away from fat quantity to fat quality. Despite these recommendations and years of bad publicity in terms of the adverse affects of animal fats in human health, the livestock industry seems reluctant to shift its focus to fat quality rather than quantity. This approach may adversely affect future meat consumption by consumers who are becoming increasingly critical about the food they eat. PMID- 22063168 TI - The taste of fat. AB - For many years, fat in meats have been considered to convey quality although variations in the amounts of fat were often poorly correlated with eating qualities. The contribution of fat to taste is equally controversial, because a specific 'fat taste' perception had not been characterized. The innate attraction for fats may be due to one or more of orosensory, post-ingestive and metabolic signals. This literature review suggests that taste of lipids, particularly of oxidized PUFAs and their esters, may derive from a specific fatty acid perception mechanism in human lingual papillae. Interactions of the CD36 scavenger system with the many compounds derived from fats in cooked and processed meats offer an explanation for the variety of flavors and off-flavors found in meats. The genetic variations in the presence of receptor proteins could be one of the factors related to the differences in fat preferences in different countries and between genders. PMID- 22063169 TI - Where is MAP Going? A review and future potential of modified atmosphere packaging for meat. AB - Modified atmosphere packaging (MAP) is the removal and/or replacement of the atmosphere surrounding the product before sealing in vapor-barrier materials. While technically different, many forms of MAP are also case-ready packaging, where meat is cut and packaged at a centralized location for transport to and display at a retail store. Most of the shelf life properties of meat are extended by use of MAP, but anoxic forms of MAP without carbon monoxide (CO) do not provide bloomed red meat color and MAP with oxygen (O(2)) may promote oxidation of lipids and pigments. Advances in plastic materials and equipment have propelled advances in MAP, but other technological and logistical considerations are needed for successful MAP systems for raw chilled fresh meat. Current MAP options of air-permeable overwrapped trays in master packs, low O(2) formats of shrunk film vacuum packaging (VP) or MAP with carbon dioxide (CO(2)) and nitrogen (N(2)) and their peelable barrier film derivatives, and high O(2) MAP each have advantages and disadvantages. Packaging technology innovations and ingenuity will continue to provide MAP that is consumer oriented, product enhancing, environmentally responsive, and cost effective, but continued research and development by the scientific and industry sectors will be needed. PMID- 22063170 TI - Post-slaughter traceability. AB - Traceability programs can cover the whole of life, or parts of it, for individual animals or groups/lots of animals. Of 13 country or community traceability programs for cattle/beef, 11 are mandatory (4 encompass, or are scheduled to encompass, birth to retail; 7 cover birth to slaughter) while 2 are voluntary and encompass birth to slaughter. Of 10 country or community traceability programs for swine/pork, 2 are mandatory (1 covers birth to retail; 1 covers birth to slaughter) while 8 are voluntary. Of 6 country or community traceability programs for sheep/sheep-meat, 3 are mandatory (1 encompasses birth to retail; 2 encompass birth to slaughter) while 3 are voluntary. Mandatory birth to retail programs that include "post-slaughter individual animal identification (IAID) traceability" have been implemented for cattle/beef, swine/pork and sheep/sheep meat by the European Union and for cattle/beef by Japan. Many of the voluntary as well as mandatory, birth to slaughter traceability programs for all three species are presumed (though that is not specified) to include "post-slaughter group/lot identification (GLID) traceability" - e.g., those qualifying products for shipment to the European Union. "Post-slaughter IAID traceability" can be accomplished in very-small, small, medium, large and very-large packing plants using single-carcass processing units, tagging and separation/segregation, and/or deoxyribonucleic acid (DNA) fingerprinting technology but all of these approaches are time-consuming and costly; and, to-date, in most countries, there has been no reason compelling enough to cause industry to adopt such protocols or technology. PMID- 22063171 TI - Probiotics in fermented sausages. AB - Probiotic foods receive market interest as health-promoting, functional foods. They have been introduced in a wide range of food industries. However, commercial application of probiotic microorganisms in fermented sausages is not common yet. There are both advantages and disadvantages connected to fermented meat matrices. They are adequate for the carriage of probiotic bacteria since they are usually not or only mildly heated and may promote the survival of probiotic bacteria in the gastrointestinal tract. In contrast, bacterial viability may be reduced due to the high content in curing salt and the low water activity and pH. Therefore, results are expected to be strain-dependent. Up till now, several approaches have been followed but most results are too preliminary to be able to evaluate the effect of probiotic fermented meats on human health. Candidate probiotic strains have been obtained through screening for technological requirements among bacteria that are naturally present in the meat or that originate from meat starter cultures. Alternatively, existing probiotic bacteria have been applied in meat products. Finally, the evaluation of the end-products needs to deal with both health effects and technological characteristics, for instance through human intervention studies and taste panels, respectively. PMID- 22063172 TI - Present and future applications of DNA technologies to improve beef production. AB - Substantial improvements in production efficiency and quality of beef and dairy products have been made possible through manipulation of bovine genetics. The advent of modern breeds in the last two centuries, the institution of phenotypic selection practices and quantitative genetics, even the process of domestication in the distant past, have all represented means to make use of naturally occurring variation in the genome to tailor the animal for a desired outcome. We discuss the history of genome research in cattle and recent technological advances that promise a leap forward in the use of DNA sequence to facilitate selection, in which a detailed genome-level view for individual animals may provide comprehensive and relatively accurate assessment of the consequences, both desired and unintended, of genetic selection for livestock production. PMID- 22063173 TI - Do indigenous Southern African cattle breeds have the right genetics for commercial production of quality meat? AB - The establishment of cattle breeds which are now indigenous to Africa is believed by historians to be very closely associated with man, his development, migration and specific behaviour from 6000 years BC. Today these breeds compete with exotic breeds in a commercial system driven by global economical principles. Results from various trials are discussed to verify if these breeds can adhere to these principles and compete in the South African beef market to produce quality beef economically. Variation in frame size among indigenous breeds will determine their suitability as feedlot cattle depending on the price and feed margins driving profit in this industry sector. Meat quality analyses indicate small or no differences between indigenous and exotic European/British breeds but with potentially superior quality compared to Bos indicus breeds. PMID- 22063174 TI - The yield and nutritional value of meat from African ungulates, camelidae, rodents, ratites and reptiles. AB - The current knowledge of the yield and nutritional (proximate and fatty acid) composition of meat derived from African ungulates, camelidae, rodents, ratites and reptiles is reviewed. Although most of the species discussed give low cholesterol levels consistent with their low meat lipid contents, the tegu lizard gives a very low level (18.2mg/100g tissue). The fatty acid profiles of the various species all have low saturated fatty acids and high polyunsaturated fatty acids resulting in favourable saturated to polyunsaturated fatty acid ratios. Although the springbok, camel, ostrich and crocodile are marketed and exported to sophisticated markets, the rodents are the species that show most promise in becoming large commercial commodities. Not only is their meat desirable and nutritional, but they are also highly adaptable to extensive and intensive production systems. PMID- 22063175 TI - The contribution of chevon from Africa to global meat production. AB - Africa's goat population increased by 75% between 1980 and 2005 and constitutes 30% of the world goat population. Although Africa produces about 20% of the world's chevon, its share of world chevon market has been declining. Exports from Africa represent less than 5% of the total world trade. Most goats are raised by smallholder farmers for subsistence and trading in informal markets. The world renowned Boer, Kalahari Red and Savanna goats are meat breeds that were developed in South Africa. Information on most African goat breeds is scanty, but there seems to be large variations in the breed characteristics, which suggests a potential for selective breeding for more and meat breeds. Recommendations for enhancing goat production in Africa include, prioritizing research and technology transfer on meat goat production, development of more chevon breeds, devising methods to enhance the quality of African chevon through pre- and post-harvest interventions, and improved support from government institutions and policy. PMID- 22063176 TI - Reassessing the principles of electrical stimulation. AB - The mechanisms by which electrical stimulation (ES) of carcasses can be used to modulate meat quality are reviewed. Evidence to support an effect of ES on tenderness (and other meat quality attributes) based solely on changes in the pH/temperature profile within carcass muscles are presented. The interactions between electrical parameters and the contraction responses of carcass muscles are described to provide generalised principles to guide the design of electrical stimulation technology. The commercial risks to meat quality of inappropriate use of electrical stimulation, particularly excessive stimulation to produce PSE-like conditions, are considered. PMID- 22063177 TI - Modelling quality variations in commercial Ontario pork production. AB - This study explores the interactions of sensory and nutritional environment with genotype occurring in current commercial pork production in Ontario, Canada, which may interact to result in poor quality meat. The study focussed on identifying factors and signalling mechanisms that contribute to poor meat quality, in order to develop strategies to reduce the incidence of unacceptable product quality. In the first phase of the work reported here, animal behaviour and muscle metabolism studies were related to meat colour, tenderness and water holding capacity measurements from commercially-produced pigs killed in a commercial packing plant. A partial least squares analysis was used to determine the most important of the principal production variables, peri-mortem biochemical measures and post-mortem carcass condition variables studied, in terms of their influence on water-holding, toughness and colour (L*-value). Variations between producer and kill day at the slaughterhouse were very strong contributors to variability in these three meat quality parameters, followed by pH variations. A second phase of the study is currently underway to characterize patterns of gene expression related to extremes of end-product quality and to reduce quality variations by nutritional and behavioural management strategies. PMID- 22063178 TI - Meat quality assessment using biophysical methods related to meat structure. AB - This paper overviews the biophysical methods developed to gain access to meat structure information. The meat industry needs reliable meat quality information throughout the production process in order to guarantee high-quality meat products for consumers. Fast and non-invasive sensors will shortly be deployed, based on the development of biophysical methods for assessing meat structure. Reliable meat quality information (tenderness, flavour, juiciness, colour) can be provided by a number of different meat structure assessment either by means of mechanical (i.e., Warner-Bratzler shear force), optical (colour measurements, fluorescence) electrical probing or using ultrasonic measurements, electromagnetic waves, NMR, NIR, and so on. These measurements are often used to construct meat structure images that are fusioned and then processed via multi image analysis, which needs appropriate processing methods. Quality traits related to mechanical properties are often better assessed by methods that take into account the natural anisotropy of meat due to its relatively linear myofibrillar structure. Biophysical methods of assessment can either measure meat component properties directly, or calculate them indirectly by using obvious correlations between one or several biophysical measurements and meat component properties. Taking these calculations and modelling the main relevant biophysical properties involved can help to improve our understanding of meat properties and thus of eating quality. PMID- 22063179 TI - Lipid composition and lipolytic enzyme activities in porcine skeletal muscles with different oxidative pattern. AB - Three muscles with different oxidative pattern (m. longissimus dorsi, Ld; m. biceps femoris, Bf; m. triceps brachii, Tb) have been analysed for lipid composition and lipolytic activities. The results showed a relatively low lipid (around 30 g kg(-1)) and cholesterol (around 0.5 g kg(-1)) content being higher in the oxidative and intermediate muscles Tb and Bf, respectively, than in Ld. Muscle Tb had higher amount of phospholipids and PUFA. Muscle Tb also had the higher lipolytic activity (acid and neutral lipase and acid phospholipase activities). There were no differences for acid and neutral esterase activities between the three muscles studied. The use of principal component (PC) analysis might be used to distinguish among the three studied muscles since each one showed a different pattern based on the lipid composition and lipolytic activities. PMID- 22063180 TI - Proteolytic activity of Lactobacillus strains isolated from dryfermented sausages on muscle sarcoplasmic proteins. AB - The proteolytic activity of seven strains of Lactobacillus from two species isolated from dry cured sausages was assayed using a soluble muscle extract as a source of proteins, at a temperature of 30 degrees C. The results indicated that the strains of Lactobacillus plantarum tested had the more active proteolytic system, showing the highest amino acid release in the medium after 72 hr of incubation (L. plantarum CRL 681) when the microorganism was in the stationary phase of growth. The strains of L. casei showed a continued hydrolytic activity with a lower amino acids concentration along the studied period. The SDS-PAGE profiles showed that the major changes in sarcoplasmic proteins were produced in the 13 kDa and 36-40 kDa molecular weights region. PMID- 22063181 TI - Tenderness of normal and callipyge lamb aged fresh or after freezing(*). AB - The present experiments were conducted to determine if tenderness differed between normal (N) and callipyge (CLPG) lamb during post-mortem aging of: (1) longissimus muscle (LM), (2) semimembranosus muscle (SM), and (3) LM after freezing for 6 weeks. In the LM, CLPG chops were tougher (p < 0.01) than N at every post-mortem age and after 24 h CaCl(2) marination of a day 1 chop. Post mortem aging reduced (p < 0.05) shear force of the LM in both N and CLPG; however, this reduction proceeded at a slower rate (-0.127 vs -0.341 kg d(-1); p = 0.01) and for a longer time period (24 vs 6 days; p < 0.05) in CLPG than N. In the SM muscle, shear force values did not differ (p > 0.05). due to phenotype, post-mortem age, or the two-way interaction. Freezing prior to aging accelerated the rate of post-mortem tenderization in CLPG (-0.130 vs -0.060 kg d(-1); p = 0.004) while no changes (p > 0.05) were observed for N. Phenotypic expression of the CLPG gene increased the toughness of the LM with no change in SM; however, freezing prior to aging accelerated the post-mortem tenderization process in CLPG LM. PMID- 22063182 TI - Effect of muscle type, packaging, and irradiation on lipid oxidation, volatile production, and color in raw pork patties. AB - Effects of packaging and irradiation combinations on lipid oxidation, off-flavor, and color changes of raw patties prepared from three pork muscles were studied. Patties were prepared from each of the ground L. dorsi (L. thoracis and lumborum), psoas, and R. femoris muscles of pig, packaged either in oxygen permeable polyethylene bags or impermeable nylon/polyethylene bags, irradiated with an electron beam at 0 or 4.5 kGy dose, and then stored up to two weeks at 4 degrees C. Lipid 8 oxidation and color of the patties were determined after 0, 3, 7, and 14 days of storage, and volatiles 24 hr after irradiation. Irradiation and high fat content accelerated the lipid oxidation in raw meat during storage. Oxygen availability during storage, however, was more important than irradiation on the lipid oxidation and color values of raw patties. Irradiated meat produced more volatiles than nonirradiated patties, and the proportion of volatiles varied by the packaging-irradiation conditions of patties. Irradiation produced many unidentified volatiles that could be responsible for the off-odor in irradiated raw meat. No single volatile components but total volatiles, however, could be used to predict lipid oxidation status of raw meat. PMID- 22063183 TI - Effect of halothane genotype on porcine meat quality and myoglobin autoxidation. AB - The objective of this study was to determine effects of light (40-80 kg) or heavy (100-130 kg) slaughter weight and halothane status (positive, nn; negative, NN; and heterozygous, Nn), on meat quality. Longissimus muscle (LM) pH at 45 min (pH(45)) post-exsanguination was 6.25, 6.03, and 5.84 (different at p < 0.01) for NN, Nn, and nn genotype, respectively. At heavier weights (100-130 kg), genotype correlated (r = -0.71) with LM pH(45), 10th costae LM (TENLM) color score (r = 0.55), TENLM Hunter L(*)-value (r = 0.47), water holding capacity (r = 0.42) and TENLM subjective firmness-wetness score (r = 0.51). Rate constants for metmyoglobin accumulation and oxymyoglobin autoxidation, indicators for fresh meat color stability, increased (p < 0.05) with decreasing pH. Color stability for NN muscle was more stable than nn muscle (p < 0.05). Electrofocusing of myoblobin revealed two bands (MW 17.10(3)) at pI 6.1 and 6.5 across genotypes. Because differences were not observed across genotypes, an observed increase (p < 0.05) in 24 hr myoglobin autoxidation rate constant (associated with increased expression of the HAL gene) are presumed dependent upon post-mortem muscle changes. These data show that changes in halothane status affect fresh pork quality and that lowered meat quality results in further color destruction due to altered chemical reactions involving myoglobin oxidation. PMID- 22063184 TI - Influence of dietary beta-alanine and histidine on the oxidative stability of pork. AB - Carnosine (beta-alanine-L-histidine) and anserine (beta-alanine-1-methyl histidine) are endogenous antioxidants found in skeletal muscle. The objective of this research was to determine if supplementation of swine diets with histidine (histidine; 0.40%) and/or beta-alanine (beta-alanine; 0.225%) was an effective method to increase carnosine and anserine concentrations and the oxidative stability of Longissimus dorsi (LD) and Vastus intermedius (VI) muscles. Dietary treatments had no effect on carnosine and anserine concentrations in LD; however, histidine + beta-alanine supplementation increased carnosine and anserine in VI muscle compared to beta-alanine supplementation. Dietary supplementation had no effect on the formation of thiobarbituric acid reactive (TBARS) or lipid peroxides in cooked VI and LD. In salted VI and LD muscle, differences in TBARS and peroxides were observed; however, these differences did not consistently correlate with differences in anserine and carnosine concentrations. Therefore, the results of this research suggest that supplementation of swine diets with beta-alanine and/or histidine is not an efficient method to increase the oxidative stability of pork. PMID- 22063185 TI - Effects of anka rice, nitrite, and phosphate on warmed-over flavor and palatability characteristics in roast beef. AB - Effects of anka rice, nitrite, and phosphate used in surface curing of roast beef on chemical analysis, lipid oxidation, sensory evaluation, physical measurements, and microbial growth after refrigerated storage were studied. TBA values indicated that nitrite retarded lipid oxidation and inhibited development of warmed-over flavor; however, anka rice had a flavor masking effect on oxidation; and phosphate did not improve physical measurements due to surface curing but slightly inhibited oxidation. There was a synergistic effect among anka rice, nitrite, and phosphate in some measurements. PMID- 22063186 TI - Effects of chopping time, meat source and storage temperature on the colour of New Zealand type fresh beef sausages. AB - The colour stability of finely chopped fresh sausages made from post-rigor, pre rigor salt added (1.5% w/w) or pre-rigor no salt added beef mince was evaluated using a Hunter Miniscan (L (*) a (*) b (*)) and sensory colour panel. Batters were chopped for various times and sausages stored at -1.5 degrees , + 4.0 degrees and + 8.0 degrees C. Regardless of meat source or chopping time, colour stability was greatest at -1.5 degrees C. Panellists found the colour of all sausages stored at -1.5 degrees C acceptable for at least six days. Sausages made from unsalted pre-rigor mince had markedly better colour stability than those made from the other meats, especially when stored at 4 degrees C or 8 degrees C. PMID- 22063187 TI - Effect of pelvic suspension and cooking temperature on the tenderness of electrically stimulated and aged beef, assessed with shear and compression tests. AB - Electrically stimulated carcass sides of young bulls were suspended at 1 hr post mortem from the aitch bone (pelvic suspension; PS) and Achilles tendon (AT), respectively. After an ageing period of 14 days at 3 degrees C, shear force (SF) and compression (20 and 80% compression) tests of the Mm. longissimus lumborum et thoracis (LO) and semimembranosus (SM) were conducted in raw muscle and after heating for 1 hr at 55, 60, 65, 70 and 80 degrees C. Collagen content was higher in SM than in LO, while sarcomere length (SL) of raw muscle were 1.75 and 1.78, for LO and SM. In comparison with the AT-side, PS increased SL by 21 and 47% and cooking loss (at 80 degrees C) by 2 and 6% for LO and SM, respectively. Drip loss of whole muscles from the PS-side during the ageing period tended to be lower (n.s.). Over the whole cooking temperature range, SF-values were relatively high for the SM in comparison with LO. For both muscles from the AT-side, the lowest SF-values were observed at 60 and 65 degrees C. The PS-treatment resulted in higher SF- values for raw muscle and after cooking at low temperatures (55 and 60 degrees C), particularly in the SM. In the intermediate temperature range (65 and 70 degrees C), PS had no significant effect, while in the higher temperature range (80 degrees C), SF-values were lower in the PS-side. Similar tendencies were observed in the LO, although the lower SF-values for the PS-side were observed already at 60 degrees C. In non-destructive compression (20%), there was a gradual increase in stress values with increasing cooking temperature. In comparison with the AT-side, the PS treatment resulted in the LO in similar or higher, and in the SM in lower stress values. With destructive compression (80%), PS resulted in SM in higher stress values in raw muscle and at 55 degrees C, in accordance with the SF-values. It is suggested that the higher SF- and 80% compression values in raw muscle and at low cooking temperatures, are caused by an increase in collagen strength due to a change in the direction and spatial organisation of the collagen fibres as a result of stretching of the muscle. This study demonstrates that the relative contributions of the collagen and myofibrillar components to the mechanical assessed toughness, as well as the effect of pelvic suspension, is dependent of muscle, cooking temperature and the mechanical test applied. PMID- 22063188 TI - Effect of calf feeding regimes and diet EDTA on physico-chemical characteristics of veal stored under modified atmospheres. AB - Physico-chemical characteristics of veal from 30 calves allotted to five different rations with respect to iron bioavailability were evaluated at packaging and after 2 and 4 weeks of storage under both 100% CO(2) and 100% N(2). The five diets were 'Milk', 'Grain', 'Mix' (combination of Milk and Grain) and 'Mix + EDTA' and 'Grain + EDTA' where 15 mg EDTA were added per mg Fe in the feed concentrate. Diet EDTA was generally more influential on veal quality than storage treatments. The chelator caused an unexpected pH drop in veal stored four weeks irrespective of storage conditions (p <= 0.05). However, the colour, texture and flavour of meat from animals fed EDTA in the Grain- and Mix-ration was equivalent to that of Milk-fed veal (p <= 0.05). The EDTA treatments also improved the appearance of veal under anoxic atmospheres. Upon storage however, the chelator increased veal drip losses (p <= 0.05) and also cooking losses from Grain-fed calves (p <= 0.05). Packaging under CO(2) decreased pH (p <= 0.05) and increased drip losses (p <= 0.05) but did not alter other physico-chemical parameters. Dietary treatments had no effect on shear forces (p > 0.05) which decreased after two weeks in storage (p <= 0.05) independent of gas atmospheres. Overall, the quality characteristics of pale veal were obtained following addition of EDTA in Grain- and Mix-fed animals and were maintained in storage. This approach looks promising for the veal industry but warrants further research. PMID- 22063189 TI - Comparison of some physical and chemical properties of selected game meats. AB - There were no significant differences in proximate composition of the different game meats. Game meats were similar in composition to beef, though beef had lower crude fat contents than expected. Myoglobin content was highest in zebra meat and lowest in oryx meat and there were significant differences (p < 0.01) between zebra and kongoni on one hand and oryx and beef on the other. Leg had higher myoglobin contents than loin. Kongoni, oryx and beef lipids consisted mainly of saturated fatty acids while those in zebra lipids were predominantly unsaturated. Zebra meat was darker than meat from other species due to its high myoglobin content. Oryx meat had the highest lightness (L (*)), and chromaticity (a (*) and b (*)) values. This gave it a bright appearance compared to the other species, though zebra meat had the highest hue angle value and thus redness. However, both oryx and kongoni meats showed a tendency to accumulate metmyoglobin at the surface. Zebra meat had less cooking loss compared to meat from the other species, including beef. PMID- 22063190 TI - Calpains and calpastatin from cold-shortened bovine M. longissimus lumborum. AB - Sections of beef longissimus lumborum from four animals were held after 1 hr post mortem at either 0 degrees (cold-shortened) or at 15 degrees C (controls). After 24 hr, the levels of MU- and m-calpains were the same in both treatments and about 30% and 85% of their initial levels respectively. The level of calpastatin at 24 h was higher in cold-shortened (100%) than in controls (60% of its initial level). During subsequent storage at 4 degrees C, the activities of calpains and calpastatin decreased similarly in extracts from both cold-shortened and control muscles. The similar levels of MU-calpain during the first 24 hr post mortem but at the lower temperature suggest that there is less activity under cold-shortening conditions. This, combined with the increased calpastatin levels, would produce less proteolysis by the calpain system. Reduced proteolysis is therefore a factor which should be considered in an understanding of the mechanism of cold-shortening toughness. PMID- 22063191 TI - Assessment of polyaromatic hydrocarbon degradation by potentially pathogenic environmental Vibrio parahaemolyticus isolates from coastal Louisiana, USA. AB - A presumed Vibrio parahaemolyticus isolate from Chesapeake Bay, Maryland, USA was previously reported to grow on phenanthrene, a polyaromatic hydrocarbon (PAH) found in crude oil. Following the Deepwater Horizon oil spill in the Gulf of Mexico, concerns were raised that PAH-degrading V. parahaemolyticus could increase in abundance, leading to elevated risks of disease derived from shellfish consumption. To assess this possibility, we examined responses to naphthalene and phenanthrene of 17 coastal Louisiana environmental V. parahaemolyticus isolates representing five distinct genotypes. Isolates were obtained immediately after the spill began and after oil had reached the Louisiana coast. None of the isolates grew on or oxidized either substrate and a naphthalene degradation product, 1-naphthol, substantially inhibited growth of some isolates. The use of PAH by V. parahaemolyticus is unusual, and an increase in human health risks due to stimulation of V. parahaemolyticus growth by oil derived PAH under in situ conditions appears unlikely. PMID- 22063192 TI - The association between in utero hyperinsulinemia and adolescent arterial stiffness. AB - AIM: To determine the relationship between in utero hyperinsulinemia and children's arterial stiffness at adolescence. METHODS: Indices of arterial stiffness were measured using the SphygmoCor apparatus in 129 adolescents (42 offsprings of mother with gestational diabetes and 87 offsprings of mother with normal glucose tolerance during pregnancy) at 15 years of age. RESULTS: Adolescent of mothers with gestational diabetes had similar central aortic blood pressure, augmentation pressure (AP), augmentation index (AI), and carotid femoral pulse wave velocity (PWV) as that of controls. However, both umbilical cord C-peptide and insulin levels correlated positively AI (R=0.28 and 0.24; p=0.011 and 0.035, respectively), and umbilical insulin level correlated positively with AP (R=0.25; p=0.025). The correlations were significant between umbilical cord C-peptide and AP (R=0.24; p=0.035) and AI (R=0.29; p=0.011) after adjustment for subjects' age, sex, body weight and height. Adolescents who had umbilical cord C-peptide levels at highest quartile (n=25), based on the reference ranges of the original cohort, had a significant greater PWV (5.26+/ 0.12 m/s vs 4.98+/-0.12 m/s; p=0.0049) than those with C-peptide levels at the lower 3 quartiles (n=57) after adjustment for age, sex, body weight and height. CONCLUSIONS: In utero hyperinsulinemia appears to increase the offspring's arterial stiffness at early adolescence. PMID- 22063193 TI - Suppression of high pacing-induced ANP secretion by antioxidants in isolated rat atria. AB - Reactive oxygen species (ROS) are formed as a natural by-product of the normal metabolism of oxygen and have important roles in cell signaling. The aim of this study was to investigate direct effects of ROS on atrial hemodynamics and ANP secretion in isolated perfused beating rat atria with antioxidants. When atria were paced at 1.2 Hz, N-acetyl cystein (antioxidant, NAC), alpha-lipoic acid (antioxidant), tempol (superoxide dismutase mimic), and apocynin (NADPH oxidase inhibitor; NOX inhibitor) did not affect ANP secretion and atrial contractility. When pacing frequency was increased from 1.2 Hz to 4 Hz, the ANP secretion increased and atrial contractility decreased. H(2)O(2) level was increased in perfusate obtained from atria stimulated by high pacing frequency. NAC, alpha lipoic acid and tempol attenuated high pacing frequency-induced ANP secretion but apocynin did not. In contrast, pyrogallol (a superoxide generator) augmented high pacing frequency-induced ANP secretion. NOX-4 protein was increased by high pacing stimulation and in diabetic rat atria. In diabetic rat atria, high pacing frequency caused an increased ANP secretion and a decreased atrial contractility, that were markedly attenuated as compared to control rats. NAC and apocynin reduced high pacing frequency-induced ANP secretion in diabetic rat atria. These results suggest that intracellular ROS formation partly through an increasing NOX activity in response to high pacing frequency is associated with an increased ANP secretion in rat atria. PMID- 22063194 TI - Capillary gel electrophoresis versus SDS PAGE of exudate from fresh pork. AB - This investigation compared electrophoretic profiles of exudate from fresh normal pork in which the protein separation was undertaken by both sodium dodecyl sulphate polyacrylamide gel electrophoresis SDS PAGE and capillary gel electrophoresis. The profiles obtained using the two techniques were similar and in many investigations either method would be suitable. It is suggested that capillary gel electrophoresis offers a number of benefits over the traditional time consuming and labour intensive gel electrophoresis techniques which involves gel preparation, sample application, staining and eventually quantification of the zones by densitometry. For separation of proteins in meat-based systems the advantages of capillary gel electrophoresis include on-capillary detection, instrumental automation, rapid analysis time and low sample volumes while providing similar information to that obtained from SDS PAGE. PMID- 22063195 TI - Freezing and thawing rate effects on drip loss from samples of pork. AB - The effects of six freezing rates, two storage times and three thawing rates on the drip loss from small samples (approximately 6 g) of pork were studied. Drip was collected by centrifugal extraction. Protein denaturation of the meat sample was analysed by differential scanning calorimetry. At fast freezing rates, drip losses obtained were not significantly different from that of fresh samples. At the slower freezing rates studied, drip losses were greater than that from fresh samples. After four weeks storage, drip losses were significantly greater at the slow freezing rates compared to the samples without storage. However, for the stored samples, there were no differences in drip losses with respect to the initial freezing rates. Furthermore, the drip losses from stored samples were not significantly different from drip losses of samples at the slow freezing rates without storage. No differences in denaturation profiles of the meat samples, composition of drip or total protein concentrations in the drip samples were observed. PMID- 22063196 TI - Freezing rate and frozen storage effects on the ultrastructure of samples of pork. AB - Cryo-scanning electron microscopy was used to study the ultrastructure of small samples (approximately 6 g) of pork. Combinations of six freezing rates, two storage times and three thawing rates were used. Cavities created after sublimation of the ice crystals were quantitatively analysed using an image analysis software package. The cross-sectional areas of cavities of meat samples in the frozen state were approximately ten times the areas of the cavities of the fresh and thawed samples. The large cavities in the frozen state grossly distorted the muscle cell structures. Upon thawing, the meat structure had almost completely recovered. No significant freezing rate effects were observed, however, trends were evident. Significant storage time effects were observed. In the frozen state, at the 90th percentile level, the hole area fraction was greater in stored samples for intermediate cavity areas. In thawed samples, hole area fractions of stored samples were greater than in samples without storage. PMID- 22063197 TI - A preliminary investigation of the effects of frozen storage on samples of pork. AB - The effects of combinations of freezing, thawing and frozen storage on the drip loss and ultrastructure of small samples (approximately 6 g) of pork were studied. Samples were stored for up to 12 weeks at -20 degrees C or for up to 4 weeks at temperatures fluctuating between -10 and -3 degrees C. Drip was collected by centrifugal extraction. Cryo-scanning electron microscopy was used to study the ultrastructure of the meat. Sizes of cavities created after sublimation of the ice crystals were quantitatively analysed using an image analysis software package. Freezing rate by storage time interactions were observed in drip loss analyses. No differences were observed in the drip protein concentration or electrophoretic patterns. Ultrastructural differences were only observed after thawing samples stored at the higher temperatures. The effects being investigated were subtle. PMID- 22063198 TI - Low voltage electrical stimulation of lamb carcasses: effects on meat quality. AB - The effects of an early post mortem low voltage electrical stimulation (28 V, 60 Hz) on biochemical changes and on final tenderness in muscles Longissimus thoracis et lumborum and Semimembranosus from lamb carcasses were studied. It was shown that electrical stimulation accelerated the glycolytic process resulting in a significant fall in pH during the first 6 h post mortem in both muscles examined and in a significant reduction in adenosine triphosphate (ATP) content in muscle Longissimus thoracis et lumborum. The effect of electrical stimulation on tenderness was recorded by measuring shear force values 2 and 7 days post mortem. Tenderness was significantly improved by electrical stimulation for the Longissimus thoracis et lumborum both at 2 and at 7 days post mortem, while for Semimembranosus electrical stimulation significantly increased tenderness just at 7 days post mortem. PMID- 22063199 TI - The effects of a starter culture on the formation of biogenic amines in Turkish soudjoucks. AB - The effects of starter culture containing Lactobacillus sake, Pediococcus pentosaceus, Staphylococcus carnosus plus Staphylococcus xylosus on the formation of biogenic amines during ripening of Turkish soudjoucks were investigated. Determination of eight different biogenic amines was carried out by reverse-phase high performance liquid chromatography (HPLC) using diode array detection. It was found that aerobic plate counts (APC) decreased in the samples with added starter culture. Lactic acid bacteria counts increased in both the controls and samples with added starter during ripening. Total Enterobacteriaceae (ENT) counts decreased on the 30th day for vacuum packed and starter added samples. Yeast counts decreased only in vacuum packed and starter added samples on the 30th day. No biogenic amines were found in ground meat samples. Putrescine (PU) and tyramine (TYR) were determined in all control samples during the storage at 4 degrees C. Starter addition inhibited formation of PU but not TYR. PMID- 22063200 TI - Changes in intramuscular connective tissue and collagen solubility of bovine m.semitendinosus during retorting. AB - Vacuum-packed slices of bovine m.semitendinosus (ST) muscle were retorted to internal temperatures of 50, 60, 70, 80, 90, 100 and 121 degrees C. Changes in the microstructure of the endomysium and perimysium were evaluated using a scanning electron microscope (SEM). Changes in solubility of intramuscular collagen were also estimated. In samples heated to 50 degrees C changes in intramuscular connective tissue were not seen. At 60 degrees C granulation of the perimysium and sarcolemma was seen, and on longitudinal sections, as well as granulation, fibrous structures of perimysium were observed. At 70 degrees C increased granulation was observed. In the range 80-121 degrees C progressive compression of the meat structure was seen in the transverse sections. The percentage of soluble collagen in the meat changed little up to an internal temperature of 60 degrees C, but at 70 degrees C it almost doubled, and in the range 80-121 degrees C drastically decreased. PMID- 22063201 TI - Post-mortem variation in pH, temperature, and colour profiles of veal carcasses in relation to breed, blood haemoglobin content, and carcass characteristics. AB - A total of 1764 male calves of the Meuse-Rhine-Yssel (MRY) and Friesian-Holstein (FH) breeds were slaughtered at two commercial slaughterhouses to investigate the variation in pH, temperature, and colour of Dutch veal carcasses processed without electrical stimulation and with a moderate chilling regimen (average temperature of the longissimus lumborum muscle at 45 min, 3, 24, and 48 h post mortem was 38.4, 23.3, 3.7 and 1.9 degrees C, respectively). Blood haemoglobin content was determined 2 weeks before slaughter. The efficacy of captive bolt stunning was scored and the carcass movements after shackling registered. Temperature and pH measurements were carried out at 45 min, and 3, 24, and 48 h after slaughter in the longissimus lumborum muscle (LL). Muscle surface colour (CieLAB-values) was measured with a colorimeter at the rectus abdominis muscle at the same times post-mortem. Carcass conformation and visual carcass colour classification were determined at 45 min post-mortem. Carcasses with a better EUROP-conformation score and heavier weight showed a higher rate of pH decline and a slower cooling rate. Slight differences in cooling systems between the slaughterhouses caused marked differences in pH and temperature profiles. Significant differences in carcass weight were observed between the MRY and FH breeds, leading to significant differences in pH and temperature profiles. Carcass colour of the two breeds was similar. Veal carcass colour in general was not related to the observed variation in post-mortem pH and temperature in the longissimus lumborum muscle and was shown to be more associated with the blood haemoglobin content. Haemoglobin content of the blood in the period before slaughter was shown to be related to the visually assessed carcass colour at 45 min post-mortem (using a 10-colour scale), as well as to the instrumentally determined L*-value, with significant correlation coefficients of 0.61 and -0.61, respectively. Repeated captive bolt stunning to obtain unconsciousness significantly decreased pH at 3 h post-mortem. The degree of carcass movement after slaughter did not influence pH, temperature, or colour profiles of the carcasses. PMID- 22063202 TI - Objective measurement of veal color for classification purposes. AB - 2300 veal calves were used to compare the ability of chromameters to measure the veal meat color on-line and to develop a relationship between instrumental and visual assessments to predict the color score according to the EC-system of classification. The meat color was assessed subjectively by 3 trained judges and objectively by 2 chromameters CR300 and CR310, 45 min post mortem on the Rectus abdominis, on the external side, skin having been removed. R(2) values reached 0.70 for the CR300 and 0.75 for the CR310. The equations of prediction classified correctly up to 87% of carcasses. These data indicate that chromameters (Minolta CR310 and CR300) can be used on-line to measure objectively veal meat color at the end of the slaughterline. PMID- 22063203 TI - Effect of type of suckling and length of lactation period on carcass and meat quality in intensive lamb production systems. AB - This study examined the effect of the type of suckling and length of lactation period on carcass characteristics and lamb meat quality in the Manchega Spanish breed. Fifty-eight lambs were divided into three groups differing in their management systems from birth to slaughter: The first group (W; n=21) was weaned at 35 days old. In the second one (HW; n=18) ewes were subjected to milking simultaneously with suckling of lambs ("half milk") from 15 to 45 days old. The third group (UW; n=19) remained with their mothers from birth to slaughter. UW lambs had higher dressing proportion (48.3%) than the other two groups, a higher fatness score (6.1) and larger amounts kidney and pelvic fat (342.63 g). Shrinkage losses and carcass conformation score did not differ among groups. Among the meat quality traits, UW lambs had higher L* parameter values (50.2). No statistical differences were found in the other parameters assessed. PMID- 22063204 TI - Feeling the pinch? PMID- 22063205 TI - Head trauma in the cat: 1. assessment and management of craniofacial injury. AB - PRACTICAL RELEVANCE: Feline trauma is commonly seen in general practice and frequently involves damage to the head. CLINICAL CHALLENGES: While craniofacial injuries following trauma vary widely in severity, affected cats can often be severely compromised in terms of their neurological, respiratory and cardiovascular status, and their management can be challenging in both the short and long term. They need prompt stabilisation and careful monitoring in the initial period to maximise prospects of a successful outcome. Many cats with severe facial trauma will require surgery to stabilise skull fractures or address injuries to the eyes, with its inherent issues surrounding pain management, ensuring adequate nutrition and the necessity for ongoing hospitalisation. DIAGNOSTICS: Cats with head trauma benefit from imaging of the injured areas as well as thoracic radiography. Imaging the skull can be challenging and is best performed under general anaesthesia. In unstable patients this can be delayed to prevent any associated morbidity. EVIDENCE BASE: The clinical evidence base relating to injury to the feline head is limited, despite its relative frequency in general practice. This review focuses on the initial approach to craniofacial (in particular, ocular and jaw) trauma, and outlines simple techniques for management of soft tissue and bone injuries. Much of the information is based on the authors' clinical experience, as there is a paucity of well-described clinical case material. PMID- 22063206 TI - Head trauma in the cat: 2. assessment and management of traumatic brain injury. AB - PRACTICAL RELEVANCE: Feline trauma patients are commonly seen in general practice and frequently have sustained some degree of brain injury. CLINICAL CHALLENGES: Cats with traumatic brain injuries may have a variety of clinical signs, ranging from minor neurological deficits to life-threatening neurological impairment. Appropriate management depends on prompt and accurate patient assessment, and an understanding of the pathophysiology of brain injury. The most important consideration in managing these patients is maintenance of cerebral perfusion and oxygenation. For cats with severe head injury requiring decompressive surgery, early intervention is critical. EVIDENCE BASE: There is a limited clinical evidence base to support the treatment of traumatic brain injury in cats, despite its relative frequency in general practice. Appropriate therapy is, therefore, controversial in veterinary medicine and mostly based on experimental studies or human head trauma studies. This review, which sets out to describe the specific approach to diagnosis and management of traumatic brain injury in cats, draws on the current evidence, as far as it exists, as well as the authors' clinical experience. PMID- 22063207 TI - CNS disease in the cat: current knowledge of infectious causes. AB - PRACTICAL RELEVANCE: Neurological disease is a relatively common reason for referral, constituting approximately 10% of the feline referral caseload. Nearly one-third to one-half of these cases may be infectious in origin. As such, an awareness of infectious diseases causing central nervous system (CNS) signs in cats, and their clinical diagnosis and management, is relevant to anyone dealing with cats on a regular basis. GLOBAL IMPORTANCE: Some conditions (eg, rabies) are more common in certain countries than others. Conditions such as feline infectious peritonitis (FIP) and toxoplasmosis are of global significance. PATIENT GROUP: Many infectious diseases may affect any feline population. Some, such as FIP, are more common in pedigree households, whereas others such as toxoplasmosis, feline immunodeficiency virus (FIV) or feline leukaemia virus (FeLV) infections, are more likely to affect a single cat with an outdoor lifestyle. EQUIPMENT: All patients benefit from thorough history taking and clinical, neurological and ophthalmic examinations, which all require minimal equipment. Infectious diseases may often be diagnosed on blood samples; however, definitive diagnosis may require more extensive investigation involving cerebrospinal fluid analysis or advanced imaging necessitating access to computed tomography or magnetic resonance imaging. EVIDENCE BASE: The information in this review, which summarises current knowledge of infectious diseases affecting the CNS, is collated from publications on the infectious diseases comprising previous research papers, review articles, case series, case reports and textbooks, supplemented by the clinical experience of the authors. PMID- 22063208 TI - Neuromuscular disorders in the cat: clinical approach to weakness. AB - PRACTICAL RELEVANCE: Weakness is a relatively common clinical presentation in feline medicine and can be caused by primary neuromuscular disease or by diseases of other body systems affecting the neuromuscular system secondarily. Successful work-up relies on a thorough clinical and neurological examination, and logical problem solving, based on an understanding of the underlying neuroanatomical and pathophysiological mechanisms. CLINICAL CHALLENGES: Feline neuromuscular diseases can be a diagnostic challenge. On initial inspection, the presenting signs can mimic disorders of other body systems, particularly cardiovascular, pulmonary and orthopaedic disease, or may be confused with systemic illnesses. Additionally, because many different pathologies of the feline neuromuscular system converge to a similar clinical phenotype, further diagnostic steps such as electrodiagnostics, cerebrospinal fluid analysis, and muscle and nerve biopsies must be considered even after neuromuscular dysfunction has been identified. AUDIENCE: This review provides a framework for the clinical approach to the weak cat and gives a practical summary of neuromuscular diseases for the general practitioner and specialist alike. EVIDENCE BASE: Many diseases affecting the feline neuromuscular system have been well described in the veterinary literature, mostly based on retrospective case reports and series. The evidence base for the treatment of feline neuromuscular diseases remains very limited. PMID- 22063209 TI - Acute spinal cord injury in the cat: causes, treatment and prognosis. AB - PRACTICAL RELEVANCE: Acute spinal conditions are a common emergency presentation in general veterinary practice and have the potential to cause devastating spinal cord injury (SCI) and consequent severe neurological deficits. SCI can be divided into two subgroups: exogenous SCI (vertebral fracture and/or luxation/subluxation) and endogenous SCI (intervertebral disc extrusion and ischaemic myelopathy). CLINICAL CHALLENGES: The majority of cats with SCI have concurrent injuries. The clinician must perform a thorough physical examination and prioritise and then stabilise the life-threatening problems before focusing on the neurological examination. The possibility of multiple sites of SCI and spinal shock can make interpretation of the neurological examination challenging. While plain radiographs or myelography are usually diagnostic, they do not give direct information about the integrity of the spinal cord parenchyma or the severity of any damage. If facilities or experienced staff capable of performing the necessary surgery are not available, or advanced imaging is indicated, referral to a specialist veterinary institution should be considered. AUDIENCE: This review is aimed at clinicians dealing with feline SCI in the emergency setting or at first-opinion level, and discusses causes, initial management, specific treatment and prognosis. PATIENT GROUP: While any cat may potentially be affected by SCI, there is a tendency for exogenous SCI to be more common in younger individuals and, in the authors' experience, pure-breed cats are very rarely presented. Endogenous SCI can be seen in any breed and is typically a condition of adult cats. PMID- 22063210 TI - Blindness and behavioural changes in the cat: common neurological causes. AB - PRACTICAL RELEVANCE: Blindness and behavioural changes occur relatively commonly in cats, either separately or in combination, causing devastating consequences for the cat and owner. Blindness can be caused by primary ophthalmic, metabolic or intracranial disease. Similarly behavioural changes may be the primary result of intracranial or systemic disease, but also occur secondarily to visual deficits or changes in interaction with the external environment (ie, non-medical problems). The anatomical pathways involved in vision are very close to those involved in behavioural regulation. It is, therefore, likely that a brain lesion (especially a forebrain lesion) that causes blindness will also cause behavioural abnormalities. CLINICAL CHALLENGES: In cases of partial or unilateral blindness, obvious visual deficits may not be apparent to the owner or clinician. Rather, the visual impairment may manifest more subtly as changes in behaviour, reluctance to jump or unwillingness to go outside. Similarly, behavioural problems may be episodic and, hence, a cat presenting with behavioural disturbances may appear clinically normal on evaluation. Behavioural changes are unlikely to be noticed unless marked and associated with bilateral blindness or advanced systemic illness. AUDIENCE: This article discusses these two major disorders separately, with the aim of highlighting for the clinician some of the important aspects of the general clinical and neurological examination that can be performed to identify these challenging cases. PMID- 22063211 TI - Deslorelin implants - a new choice in feline reproductive medicine. PMID- 22063213 TI - Effect of organic pig production systems on performance and meat quality. AB - The present study was carried out to establish knowledge of consequence for setting up guidelines of importance for production of competitive organic pork of high quality. Performance and meat quality characteristics were compared between three organic pig production systems based on indoor housing with access to an outdoor area and a Danish conventional indoor system including 100% concentrate during the finishing feeding stage. The three organic systems used the following three feeding regimes: 100% organic concentrate according to Danish recommendations, 70% organic concentrate (restricted) plus ad libitum organic barley/pea silage and 70% organic concentrate (restricted) plus ad libitum organic clover grass silage, respectively. With exception of a slightly lower daily gain in organic pigs fed 100% concentrate, no significant difference was found in performance and meat quality characteristics compared with results obtained in the conventional system. In contrast and independent of roughage used, organic pigs raised on 70% concentrate had a significant reduction in daily gain (P<0.001) compared with pigs raised on 100% concentrate, despite the fact that no difference in feed conversion rate was seen between the tested production systems. However, the percentage of leanness increased significantly in meat from organic pigs raised on 70% concentrate plus roughage compared with meat from pigs given 100% concentrate. This was reflected in higher yield (weight) of lean cuts and lower yield of cuts with high fat content from pigs fed 70% concentrate plus roughage. In general, organic feeding resulted in a significantly higher content of polyunsaturated fatty acids in the back fat (1.8%), which increased further when restricted feeding plus roughage (4%) was used. Restricted concentrate feeding gave rise to a decrease in tenderness compared with pork from pigs fed 100% concentrate. PMID- 22063212 TI - Cell autonomy of DSCAM function in retinal development. AB - Cell adhesion molecules (CAMs) provide identifying cues by which neural architecture is sculpted. The Down Syndrome Cell Adhesion Molecule (DSCAM) is required for many neurodevelopmental processes in different species and also has several potential mechanisms of activity, including homophilic adhesion, homophilic repulsion and heterophilic interactions. In the mouse retina, Dscam is expressed in many, but not all neuronal subtypes. Mutations in Dscam cause the fasciculation of dendrites of neighboring homotypic neurons, indicating a role in self-avoidance among cells of a given type, a disruption of the non-random patterning of their cell bodies, and a decrease in developmental cell death in affected cell populations. In order to address how DSCAM facilitates retinal pattering, we developed a conditional allele of Dscam to use alongside existing Dscam mutant mouse strains. Conditional deletion of Dscam reproduces cell spacing, cell number and dendrite arborization defects. Inducible deletion of Dscam and retinal ganglion cell depletion in Brn3b mutant retinas both indicate that these DSCAM-mediated phenotypes can occur independently. In chimeric retinas, in which wild type and Dscam mutant cells are comingled, Dscam mutant cells entangle adjacent wild type cells of the same type, as if both cells were lacking Dscam, consistent with DSCAM-dependent cell spacing and neurite arborization being mediated through homophilic binding cell-to-cell. Deletion of Dscam in specific cell types causes cell-type-autonomous cell body spacing defects, indicating that DSCAM mediates arborization and spacing by acting within given cell types. We also examine the cell autonomy of DSCAM in laminar stratification and find that laminar disorganization can be caused in a non-cell autonomous fashion. Finally, we find Dscam dosage-dependent defects in developmental cell death and amacrine cell spacing, relevant to the increased cell death and other disorders observed in Down syndrome mouse models and human patients, in which Dscam is present in three copies. PMID- 22063214 TI - The effects of subterranean clover phytoestrogens on sheep growth, reproduction and carcass characteristics. AB - The aim of the present study was to evaluate the effect of a prolonged administration of phytoestrogens on sheep growth rate, female reproductive response, lamb carcass conformation and meat quality. To investigate these effects, two groups of Comisana sheep (24 females and 20 males, initial average live weights of 25.0 and 29.9kg, respectively) were fed on subterranean clover (SC, phytoestrogen content=0.8mg/g of DM) and Italian ryegrass (C, non oestrogenic control diet) for about one year. Feedstuffs were offered ad libitum and supplemented with maize grain and sunflower meal to maintain an adequate and similar energy and protein intake. The results demonstrated that the prolonged administration of the selected subterranean clover cultivars, with low formononetin content (lower than 10% of total isoflavones on dry basis), did not affect ewe reproduction but induced a significant improvement in animal weigh gain and, in males, good carcass and meat characteristics. PMID- 22063215 TI - Antilisterial activity of lactic acid bacteria inoculated on cooked ham. AB - This study was conducted to evaluate the ability of Lactobacillus sakei 1, a bacteriocin-producing (bac(+)) lactic acid bacterium (LAB), isolated from Brazilian fresh pork sausage to inhibit two Listeria monocytogenes strains (serotypes 4b and 1/2a) on cooked, sliced vacuum-packaged ham. L. sakei ATCC 15521 was used as a non-bacteriocin producer (bac(-)). L. monocytogenes (ca. 2 logCFU/mL) and LAB (ca. 6 logCFU/ml) were inoculated on the sterilized ham, vacuum-sealed and incubated at 8 degrees C for 10 days. A treatment with the bacteriocin Chrisin (UI/ml) was included. Both L. monocytogenes strains were significantly inhibited in the presence of either bac(+) and bac(-) LAB in comparison to the control (L. monocytogenes alone). Using a bacteriocinogenic strain of LAB did not offer an additional barrier to listerial growth in the studied meat system. The application of Chrisin did not affect at all the growth of L. monocytogenes. PMID- 22063216 TI - Effects of a compensatory growth strategy on sensory and physical properties of meat from young bulls. AB - The objective of the present study was to investigate the sensory properties, with special emphasis on tenderness, of meat from strategically fed young bulls (13 months of age) slaughtered when a plateau in protein turnover was observed. Twelve Holstein Friesian young bulls were divided into two feeding strategies. One group of young bulls (n=6) were fed ad libitum throughout the rearing period (AD) whereas the second group (n=6) was subjected to a compensatory growth feeding strategy (CO). Sensory profiling of beef longissimus dorsi (LD), semimembranosus (SM) and supraspinatus (SS) was performed in addition to physical measurements (shear force) and content of intramuscular fat of LD. The data was analysed using a regression-based multivariate data analytical strategy. In relation to predictivity of the various shear force measurement constituents for sensory texture, it was determined that a number of the responses collected (e.g. max(mm)), in addition to the commonly used max((N)) may be utilised to predict subtlety in the sensory texture differences of the samples (e.g. Crumbliness) with respect to compensatory feeding. Through profiling LD and SS were found to have enhanced texture and flavour properties when the young bulls were fed ad libitum during rearing. However, the SM samples were found to improve in characteristics regarding texture and appearance when the young bulls had been fed compensatorily. Thus, compensatory feeding as a texture improvement strategy proved to be highly dependant on muscle type. Of note, LD and SS were found to develop an off-flavour designated as 'steer taint' when derived from compensatory feeding. This was postulated as potentially not a problem for the consumer, in LD as the level was not significant, and in SS due to sensory masking when commonly prepared as a stew or casserole. Considering the different preparation methods used for meat from LD, SM and SS, compensatory feeding may be considered to have improved the texture and elevated the eating quality where it was most relevant, namely in SM roasts. PMID- 22063217 TI - Aluminium contents in baked meats wrapped in aluminium foil. AB - In this investigation, the effect of cooking treatments (60min at 150 degrees C, 40min at 200 degrees C, and 20min at 250 degrees C) on aluminium contents of meats (beef, water buffalo, mutton, chicken and turkey) baked in aluminium foil were evaluated. Cooking increased the aluminium concentration of both the white and red meats. The increase was 89-378% in red meats and 76-215% in poultry. The least increase (76-115%) was observed in the samples baked for 60min at 150 degrees C, while the highest increase (153-378%) was in samples baked for 20min at 250 degrees C. It was determined that the fat content of meat in addition to the cooking process affected the migration of aluminium (r(2)=0.83; P<0.01). It was also found that raw chicken and turkey breast meat contained higher amounts of aluminium than the raw chicken and turkey leg meat, respectively. Regarding the suggested provisional tolerable daily intake of 1mg Al/kg body weight per day of the FAO/WHO Expert Committee on Food Additives, there are no evident risks to the health of the consumer from using aluminium foil to cook meats. However, eating meals prepared in aluminium foil may carry a risk to the health by adding to other aluminium sources. PMID- 22063218 TI - Nutrient profiles in retail cuts of bison meat. AB - The objectives were to determine the nutrient composition and variation in eight cuts of bison meat in bulls and heifers and identify nutrient relationships in the clod and sirloin by principal component analysis. The nutrients analyzed were: energy, protein, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, transfat, cholesterol, vitamin A, Ca, Fe, Na and moisture. Differences were observed in fat components between cuts and bulls had higher (P<0.05) amounts of total, saturated, monounsaturated and polyunsaturated fat in the blade compared to the other cuts. The sirloins had less (P<0.05) cholesterol than all the other cuts in bulls and the clod in heifers. Fat varied more than protein and moisture in all cuts. Four principal components (PC) accounted for 63.9% of the total variation of the nutrient composition. Total, monounsaturated and saturated fats were in PC1 and cholesterol in PC2 showing that cholesterol is independent of other fats. If dietary alterations elicit changes in bison meat fatty acid profiles, it may be possible to reduce cholesterol independent of total, monounsaturated or saturated fat. PMID- 22063219 TI - Prevalence of ballooning of the severed carotid arteries at slaughter in cattle, calves and sheep. AB - Previous work in calves indicated that ballooning of the severed arteries is a potential concern in animals receiving a reversible stun before slaughter, and in animals not stunned before slaughter, as it could extend the duration of brain function before the animals die. This study determined the prevalence of ballooning of the carotid arteries in a total of 987 cattle, calves and lambs at slaughter. The severed ends of the carotid arteries were examined by palpation. The prevalence of ballooning that was 3cm or more in diameter, was 16%, 25% and 0% for cattle, calves and lambs, respectively. Artery sections were taken from a sample of large cattle and examined histologically. In ballooned arteries there was coagulated blood between the outer surface of the artery and the inner aspect of the connective tissue sheath surrounding the artery, suggesting the formation of a false aneurysm in the ballooning phenomenon. PMID- 22063220 TI - Small peptides (<5kDa) found in ready-to-eat beef meat. AB - Dietary proteins can have biological properties, many attributed to bioactive peptides (2-50 amino acids). Since little is known about peptides in meat, we investigated the postmortem occurrence of low molecular weight peptides (<5kDa) in bovine Pectoralis profundus muscle, after 14 days storage at 4 degrees C and vacuum cooking for 90min at 75 degrees C. The study combined quantitative (amino acid analysis) and qualitative approaches (mass spectrometry). Eighty-nine percent of peptidic amino acids in fresh muscle corresponded to carnosine, anserine and glutathione. Levels of these compounds were lower in cooked meat compared to fresh muscle. Concomitantly, numerous larger compounds, most probably peptides, were generated in a very reproducible manner during ageing and even more during cooking of meat. Seven peptides (fragments of troponin T, nebulin, procollagen and cypher proteins) were identified in cooked meat extracts. PMID- 22063221 TI - Identifying market segments in beef: Breed, slaughter weight and ageing time implications. AB - In this paper we propose a method to learn the reasons why groups of consumers prefer some beef products to others. We emphasise the role of groups since, from a practical point of view, they may represent market segments that demand different products. Our method starts representing people's preferences in a metric space; there we are able to define a kernel based similarity function that allows a clustering algorithm to identify significant groups of consumers with homogeneous likes. Finally, in each cluster, we developed, with a support vector machine (SVM), a function that explains the preferences of those consumers grouped in the cluster. The method was applied to a real case of consumers of beef that tasted beef from seven Spanish breeds, slaughtered at two different weights and aged for three different ageing periods. Two different clusters of consumers were identified for acceptability and tenderness, but not for flavour. Those clusters ranked two very different breeds (Asturiana and Retinta) in opposite order. In acceptability, ageing period was appreciated in a different way. However, in tenderness most consumers preferred long ageing periods and heavier to lighter animals. PMID- 22063222 TI - A chromatography method for the screening and confirmatory detection of dexamethasone. AB - Corticosteroids, such as dexamethasone, have been illegally used as growth promoting agents to obtain an economical benefit from increased muscle development. These substances remain in meat and other animal products and may have negative toxic consequences for consumers. A screening and confirmatory method for dexamethasone detection in feed and drinking water in livestock has been developed and validated. This method is based on immunoaffinity chromatography followed by reverse-phase high-performance liquid chromatrography (IAC-HPLC) with diode array detection (DAD) at 242nm. Flumethasone was used as internal standard. The method has been validated according to the European Union regulation 2002/657/EC for banned substances and, thus, the specificity, decision limit, detection capability, recovery and repeatability have been determined. The decision limits (CCalpha) were 26ng/mL for water and 190ng/g for feed while detection capabilities (CCbeta) were 30ng/mL for water and 217ng/g for feed. The method showed good accuracy and precision. The stability of dexamethasone under frozen storage has been studied over a 3.5-month period. No losses were observed, thus confirming that water samples taken by inspectors can be stored frozen for a few weeks until analysis. This method has proved to be relatively simple and useful for rapid screening and confirmation of the presence of dexamethasone in water and feed used for meat-producing animals. PMID- 22063223 TI - Technical note: A simplified procedure for myofibril hydrophobicity determination. AB - A simple and reliable method for the determination of surface hydrophobicity of nonsolubilized myofibrils (from pig M. longissimus dorsi) was developed and validated. This method is based on the interaction of the hydrophobic chromophore bromophenol blue (BPB) with myofibrillar proteins and the separation of free and bound BPB by centrifugation. The titration of bound BPB is performed by absorption spectroscopy, and the amount of bound BPB is considered as an index of protein hydrophobicity. Heating, which is known to increase protein hydrophobicity, was performed in order to validate this method. Fixation of BPB to myofibrils increased with heating time and temperature, strongly suggesting that it may be closely related to protein hydrophobicity. PMID- 22063224 TI - NMR relaxometry and differential scanning calorimetry during meat cooking. AB - By combining simultaneous nuclear magnetic resonance (NMR) T(2) relaxometry and differential scanning calorimetry (DSC) on pork samples heated to nine temperature levels between 25 and 75 degrees C, the present study investigates the relationship between thermal denaturation of meat proteins and heat-induced changes in water characteristics. Principal component analysis (PCA) on the distributed (1)H NMR T(2) relaxation data revealed that the major changes in water characteristics during heating occur between 40 and 50 degrees C. This is probably initiated by denaturation of myosin heads, which however, could not be detected in the DSC thermograms obtained directly on the meat. In contrast, the DSC thermograms revealed endothermic transitions at 54, 65 and 77 degrees C, probably reflecting the denaturation of myosin (rods and light chain), sarcoplasmic proteins together with collagen and actin, respectively. Simultaneous modelling of DSC and NMR data by partial least squares regression (PLSR) revealed a correlation between denaturation of myosin rods and light chains at ~53-58 degrees C and heat-induced changes in myofibrillar water (T(2) relaxation time ~10-60ms) as well as between actin denaturation at ~80-82 degrees C and expulsion of water from the meat. Accordingly, the present study demonstrates a direct relationship between thermal denaturation of specific proteins/protein structures and heat-induced changes in water mobility during heating of pork. PMID- 22063225 TI - Modeling of growth and bacteriocin production by Leuconostoc mesenteroides E131. AB - Leuconostoc mesenteroides E131, isolated from dry fermented sausages, produces an antimicrobial agent, characterized as bacteriocin. The effect of pH and temperature on growth and bacteriocin production, using MRS broth as growth medium, was studied in a fermentor. The pH value at which the best cell growth was observed (6.5) did not coincided with the value at which the maximum bacteriocin activity was attained (5.5). In contrast, the maximum bacteriocin activity was attained at temperature (25 degrees C) close to the optimum temperature for cell growth (25-30 degrees C). Notably, the range of pH and temperature for good bacteriocin production was within the range used for sausage fermentation. An empirical model was developed to describe the growth and bacteriocin production in different pH and temperature conditions. The model was able to describe growth and bacteriocin production and it could be used to predict the kinetic parameters of growth and bacteriocin production within the pH and temperature range examined. PMID- 22063226 TI - Effect of feed texture, meal frequency and pre-slaughter fasting on carcass and meat quality, and urinary cortisol in pigs. AB - Carcass and meat quality traits, and urinary cortisol variation was studied in 96 barrows assigned to the following treatments: feed texture (FT; mash vs. pellets), meal frequency (MF; 2 vs. 5 meals per day) and fasting time (F; 4, 14 and 24h) according to a 2*2*3 factorial design. Pigs fed mash, receiving feed five times a day and fasted for 24h before slaughter had lower carcass dressing yield (P<0.001). A higher (P<0.05) bruise score was found on carcasses from pigs fasted for 14 and 24h and fed either pelleted or mashed feed five times per day. The pH(u) value in the Longissimus muscle increased (P<0.05) with increasing fasting time, whereas in the Adductor muscle it was higher (P<0.05) in pigs fed with pellets in two meals per day and fasted for 24h. Urinary cortisol tended to be higher in pigs fasted for 14h compared to those fasted for 4 (P=0.10) and 24h (P=0.06). The results of this study show a significant influence of pellet feeding on carcass yield in fasted pigs, while the effects of pre-slaughter fasting time on meat quality traits were limited. PMID- 22063227 TI - Effect of carbon monoxide and high oxygen modified atmosphere packaging and phosphate enhanced, case-ready pork chops. AB - The objective of this study was to evaluate the effects of CO-MAP compared to traditional high oxygen MAP (HiOx-MAP) packaging and enhanced with different phosphate on enhanced pork quality. Pork loins were enhanced to 10.5% over initial weight to contain 0.3% salt and 0.4% phosphate (either sodium tripolyphosphate [STP] or a blend of STP and sodium hexametaphosphate) on a finished weight basis. Chops were cut, packaged in atmospheres containing 0.4% CO/30.0% CO(2)/69.6% N(2) (CO-MAP) or 80% O(2)/20% CO(2) (HiOx-MAP), aged in the dark, then placed in a lighted retail display case for 48h. Chops packaged in CO MAP were redder (higher Minolta a(*) values) and darker (lower Minolta b(*) values) than chops packaged in HiOx-MAP. Based on sensory scores, the CO-MAP chops were pinker than the HiOx chops after cooking. CO-MAP chops also experienced less purge loss than chops in HiOx-MAP. Results indicate that CO-MAP had no effect on flavor or consumer acceptability and only minimal effects on other characteristics. PMID- 22063228 TI - Influence of storage period and packaging method on sliced dry cured beef "Cecina de Leon": Effects on microbiological, physicochemical and sensory quality. AB - Quality aspects of sliced dry-cured beef "Cecina de Leon" preserved in vacuum and gas mixtures (20%/80% CO(2)/N(2) and 80%/20% CO(2)/N(2)) were studied. The evolution of microbiological, physicochemical and sensory parameters were analysed during storage (210 days) at 6 degrees C. Although microbial counts at 60 days of the gas-packaged samples were lower than the vacuum-packed ones, they were never higher than the spoilage limit (7 logufc/g). A slight increase (p<0.05) in pH was observed throughout storage of "Cecina de Leon" packaged under vacuum and in gas mixtures. However, a decrease (p<0.05) in a(w) was observed during storage of "Cecina de Leon" packaged under vacuum but a(w) did not vary (p>0.05) during storage in the gas-packaged samples. No changes were observed (p>0.05) in lightness (L(*)), redness (a(*)) and yellowness (b(*)) in vacuum and gas packaged samples during storage. However, sensorially evaluated colour showed lower values in gas packaged samples during 30 days storage. This difference was decisive in establishing the shelf-life of "Cecina de Leon" slices preserved in gas mixtures (20%/80% CO(2)/N(2) and 80%/20% CO(2)/N(2)). Therefore, from a microbiological point of view, gas mixtures are more effective in extending the shelf-life of "Cecina de Leon" slices. It is concluded that vacuum packaging allows longer storage than gas-packaging as it maintains a good visual appearance of "Cecina de Leon", the main parameter in consumers' perception of meat quality. PMID- 22063229 TI - Studies on tenderization and preparation of enrobed pork chunks in microwave oven. AB - This study was conducted to develop technology for tenderization and production of enrobed pork chunks in a microwave oven. Meat chunks from shoulder cuts of pork were cured in a solution containing salt, sodium tripolyphosphate and sugar for 48h at 4+/-1 degrees C, enrobed with cream based batter and cooked in a microwave oven at 900MHz. These enrobed chunks (control) were compared with tenderized (treated) enrobed chunks, for which 7.5% cucumis extract, 9% ginger extract and 0.50% papain powder were incorporated in the standard curing solution. Ginger and papain treatments caused significant (P<0.01) increases in the moisture content and pH of the cooked products compared to the control and cucumis treated samples. Shear force values were significantly (P<0.01) lower and overall acceptability scores were significantly (P<0.01) higher in all treated samples compared to the control. During storage at 4+/-1 degrees C, the moisture contents and sensory qualities decreased, but TBARS values and microbial counts increased significantly (P<0.01). Although all products were acceptable up to 15 days of storage, the ginger treated samples had significantly (P<0.01) lower TBARS and microbial loads and higher sensory attributes than the control, cucumis and papain treated samples. The magnitude of the storage changes were less and acceptability ranking was higher for the ginger treated samples compared with the others. The results indicated that microwaves could be used for the preparation of enrobed pork chunks. The overall acceptability and shelf life of microwave cooked enrobed pork chunk can be further improved using ginger extract in the curing solution. PMID- 22063230 TI - Effects of pre-rigor injection of sodium citrate or acetate, or post-rigor injection of phosphate plus salt on post-mortem glycolysis, pH, and pork quality attributes. AB - Forty pork carcass sides were assigned to one of four treatments: pre-rigor citrate (CIT) or acetate injection (ACE); post-rigor phosphate and salt injection (PHOS); and non-injected control (CON). Loins in 20 sides were injected at 50min post-mortem with 4% solutions of CIT or ACE to approximately 110% of projected loin weights, and 10 loins were injected at 24h post-mortem to 106.6% with a solution of 4.4% PHOS and 2.2% salt. Although CIT increased pH (P<0.05), neither CIT nor ACE altered (P>0.05) glycolytic metabolite concentrations. The pH increase in muscles from the CIT treatment was most likely due to its buffering ability rather than to its glycolytic inhibition. Pre-rigor CIT injection improved tenderness without the detrimental effects on color or flavor found with PHOS, but neither CIT nor ACE altered glycolytic metabolites or improved firmness, wetness, or fresh visual color over CON. Poor flavor attributes of the ACE treatment will hinder its use as an ingredient for pork enhancement solutions. PMID- 22063231 TI - Colour and texture characteristics in meat of male and female foals. AB - The effect of livestock production system and sex was studied on the colour and on the texture profile of the longissimus dorsi muscle (LD) from 16- and 24-month old foals aged 4 days. Besides, the effect of ageing time was also studied on the texture profile between 4 and 8 days. Females from the 16-months group were darker than their counterparts and the 4-day aged steaks of the 24-month-old foals were lighter, redder and yellower. LD muscle of the 24-month-old foals was tougher after 4 and 8 days ageing than that of the younger foals besides in the 24-month-old foals the toughness may have been accentuated by lower growth rate prior to slaughter. Ageing improved tenderness but the rate of tenderisation was different according to age. The colour coordinates a(*) and b(*) could differentiate the 4-day aged steaks of the foal samples according to production system to a higher degree than did the compression or WBSF values being b(*) values the most important colour coordinate which could discriminate the origin of the animals. PMID- 22063232 TI - Impact of RN genotype and ageing time on colour characteristics of the pork muscles longissimus dorsi and semimembranosus. AB - The effect of RN genotype on pH decline, ultimate pH, pigment content, blooming and colour stability during 6 days of display at 5 degrees C was studied in two pig muscles, M. longissimus dorsi (LD) and M. semimembranosus (SM), and furthermore the effect of anaerobic storage time (2 days vs. 9 days of ageing) on the same parameters was examined. The postmortem pH decline was faster and the ultimate pH lower in LD and SM of the RN(-) genotype compared with corresponding muscles from the rn(+) genotype. Pork of the RN(-) genotype was initially lighter and more red and yellow than pork of the rn(+) genotype due to a higher degree of blooming, which might be explained by the faster pH decline and/or lower ultimate pH. The level of oxymyoglobin (MbO(2)) was decisive for the redness of both muscles during display in air despite a higher presence of metmyoglobin (MetMb). Pork of the RN(-) genotype was thus redder than that of the rn(+) genotype throughout display in air despite higher oxidation to MetMb. Ageing for 9 days in chill improved the blooming potential in pork of both genotypes compared with 2 days of ageing, resulting in superior meat colour. However, only in pork from the RN(-) genotype, the colour was not negatively affected by ageing time upon display in air. PMID- 22063233 TI - Quality of life in perspective to treatment of postoperative edema after peripheral bypass surgery. AB - BACKGROUND: To examine the effects of peripheral bypass surgery on patients' quality of life (QoL) as well as to compare two treatment modalities to reduce postoperative edema with regard to patients' QoL. METHODS: This was a randomized controlled trial set in the department of vascular surgery in a nonacademic teaching hospital. Ninety-three patients (mean age, 70 years; 33% Rutherford 5 6), enrolled between August 2006 and September 2009, who underwent peripheral bypass surgery (autologous 57, polytetrafluoroethylene 36). Patients were assigned to intermittent pneumatic compression (n = 46) or to compression stockings (n = 47). The main outcome measure was QoL, measured with the World Health Organization Quality of Life assessment instrument (short form: WHOQOL BREF). RESULTS: QoL improved on the domain of Physical Health by 7.18 points (P < 0.001 [range, 0-100]) after 2 weeks and by 10.03 points (P < 0.001) after 3 months. Patients who received a polytetrafluoroethylene bypass scored 0.45 points (P = 0.0008 [range, 1-5]) lower at baseline on Global QoL than patients who received an autologous bypass. Type of bypass or edema treatment method did not affect the improvements. Edema did not correlate with QoL. CONCLUSION: Improvement in QoL on the domain Physical Health following femoropopliteal bypass surgery was found as soon as 2 weeks after surgery. Improvement in QoL domains was not influenced by the type of bypass reconstruction. No specific effects of edema on QoL were detected. PMID- 22063234 TI - Tenderness, ageing rate and meat quality of pork M. longissimus thoracis et lumborum after accelerated boning. AB - The impact of accelerated boning on tenderness, ageing rate and meat quality of pork longissimus muscle was investigated. Accelerated boning of eight Large White*Landrace pork carcasses at 30 min post-mortem followed by chilling at 0 degrees C resulted in tougher pork with higher drip loss and a darker surface lightness relative to conventional boning at 24 h post-mortem. The increased toughness was still observed at 4 days post-mortem, a time by which 80% of ageing generally had occurred as seen in experiment 2. The increased toughness could be attributed to cold shortening and a reduction in proteolysis. PMID- 22063235 TI - Dietary manipulation of muscle long-chain omega-3 and omega-6 fatty acids and sensory properties of lamb meat. AB - The effects of dietary manipulation of muscle long-chain omega-3 fatty acids (FA) on sensory properties of cooked meat in second cross ([Merino*Border Leicester]*Poll Dorset) wether lambs were evaluated. Lambs fed dietary supplements of fish meal (FM, Exp. 1) and fish oil (FO, Exp. 2) showed moderately (P<0.01) and markedly (P<0.001) increased muscle long-chain omega-3 FA content compared with those fed the basal diet of lucerne chaff and oat chaff. Protected canola seed (PCS, Exp. 1) significantly (P<0.001) increased omega-6 FA content of the longissimus muscle. In each of the 2 experiments (1 and 2), after being fed experimental diets for 6 weeks lambs were slaughtered at a commercial abattoir. At 24 h post-mortem (PM) the semitendinosus and biceps femoris muscles were removed from animals and stored at -20 degrees C until evaluation of sensory properties using experienced panel members. The muscle samples were stored for 3 (Exp. 1) and 12 (Exp. 2) months then removed, thawed and cooked for sensory evaluation. The meat samples were cooked under standardized conditions in a convection microwave at 180 degrees C (20-25 min) to an internal temperature of 75 degrees C. Cooked samples were tested for flavour, aroma, juiciness and overall palatability. The significant increase in muscle long-chain omega-3 with FM (Exp. 1 and 2) and FO (Exp. 2) or omega-6 FA with PCS (Exp. 1) were not detrimental to sensory panel evaluations of flavour or aroma of cooked meat when compared with the basal diet. However, meat from FM (Exp. 1) had lower juiciness and FO (Exp. 2) had lower overall palatability. Protected sunflower meal protein with FO (Exp. 2) significantly lowered ratings for flavour, juiciness and overall palatability. Lamb meat with increased levels of long-chain omega-3 FA can be produced without altering the sensory quality (flavour or aroma) of the cooked meat. PMID- 22063236 TI - Predicting pork carcass and primal lean content from electromagnetic scans. AB - Fifty-four whole, pre-rigor, eviscerated carcasses (74.1+/-kg) were selected over a 5-week period to represent carcasses marketed to a Northwest Iowa packing plant during the fall season. Carcasses (spanning 40.7-65.2% carcass lean) were electromagnetically (EM) scanned before entering the chiller. Carcass right sides were fabricated and weights were recorded for each jowl, ham, loin, Boston butt, picnic shoulder, neckbone, sparerib, and belly. Each component was skinned and dissected into external fat, internal (seam) fat, bone, and lean with corresponding weights recorded. Regression equations were derived from points and areas taken from the EM scan curve. The best 5-variable equations were developed for total carcass lean (R(2)=0.9502; RMSE=1.31 kg), percentage carcass lean (R(2)=0.8789; RMSE=1.88%), ham lean (R(2)=0.8475; RMSE=0.755 kg), loin lean (R(2)=.8511; RMSE=0.781 kg), Boston butt lean (R(2)=.7251; RMSE=0.505 kg), picnic lean (R(2)=0.7387; RMSE=0.464 kg), and commodity, component carcass value (R(2)=0.9458; RMSE=$3.24). PMID- 22063237 TI - High and low rigor temperature effects on sheep meat tenderness and ageing. AB - Immediately after electrical stimulation, the paired m. longissimus thoracis et lumborum (LT) of 40 sheep were boned out and wrapped tightly with a polyethylene cling film. One of the paired LT's was chilled in 15 degrees C air to reach a rigor mortis (rigor) temperature of 18 degrees C and the other side was placed in a water bath at 35 degrees C and achieved rigor at this temperature. Wrapping reduced rigor shortening and mimicked meat left on the carcass. After rigor, the meat was aged at 15 degrees C for 0, 8, 26 and 72 h and then frozen. The frozen meat was cooked to 75 degrees C in an 85 degrees C water bath and shear force values obtained from a 1*1 cm cross-section. The shear force values of meat for 18 and 35 degrees C rigor were similar at zero ageing, but as ageing progressed, the 18 rigor meat aged faster and became more tender than meat that went into rigor at 35 degrees C (P<0.001). The mean sarcomere length values of meat samples for 18 and 35 degrees C rigor at each ageing time were significantly different (P<0.001), the samples at 35 degrees C being shorter. When the short sarcomere length values and corresponding shear force values were removed for further data analysis, the shear force values for the 35 degrees C rigor were still significantly greater. Thus the toughness of 35 degrees C meat was not a consequence of muscle shortening and appears to be due to both a faster rate of tenderisation and the meat tenderising to a greater extent at the lower temperature. The cook loss at 35 degrees C rigor (30.5%) was greater than that at 18 degrees C rigor (28.4%) (P<0.01) and the colour Hunter L values were higher at 35 degrees C (P<0.01) compared with 18 degrees C, but there were no significant differences in a or b values. PMID- 22063238 TI - Effects of sodium lactate and trisodium phosphate on the physicochemical properties and shelf life of low-fat Chinese-style sausage. AB - The efficacy of using additives to improve the shelf life of low-fat (approximately 18%) Chinese-style sausages was demonstrated. Sausages containing 3% sodium lactate (SL), 0.2% trisodium phosphate (TSP) or 0.2% potassium sorbate (KS) compared with the control (CONT) were manufactured and stored at 4 degrees C for 12 weeks. Treatment TSP was the highest in pH during any storage intervals. Generally speaking, all microbial counts were lower for SL but higher for TSP; nonetheless, all treatments had bacterial counts less than 10(7) CFU/g. Low-fat Chinese-style sausage containing 3% sodium lactate resulted in better quality regarding physicochemical and microbiological characteristics. Results also suggested a potential utilization of sodium lactate as an antimicrobial agent. PMID- 22063239 TI - Effect of muscle restraint on sheep meat tenderness with rigor mortis at 18 degrees C. AB - The effect on shear force of skeletal restraint and removing muscles from lamb m. longissimus thoracis et lumborum (LT) immediately after slaughter and electrical stimulation was undertaken at a rigor temperature of 18 degrees C (n=15). The temperature of 18 degrees C was achieved through chilling of electrically stimulated sheep carcasses in air at 12 degrees C, air flow 1-1.5 ms(-2). In other groups, the muscle was removed at 2.5 h post-mortem and either wrapped or left non-wrapped before being placed back on the carcass to follow carcass cooling regimes. Following rigor mortis, the meat was aged for 0, 16, 40 and 65 h at 15 degrees C and frozen. For the non-stimulated samples, the meat was aged for 0, 12, 36 and 60 h before being frozen. The frozen meat was cooked to 75 degrees C in an 85 degrees C water bath and shear force values obtained from a 1 * 1 cm cross-section. Commencement of ageing was considered to take place at rigor mortis and this was taken as zero aged meat. There were no significant differences in the rate of tenderisation and initial shear force for all treatments. The 23% cook loss was similar for all wrapped and non-wrapped situations and the values decreased slightly with longer ageing durations. Wrapping was shown to mimic meat left intact on the carcass, as it prevented significant prerigor shortening. Such techniques allows muscles to be removed and placed in a controlled temperature environment to enable precise studies of ageing processes. PMID- 22063240 TI - Effect of dietary fish oil on fatty acid composition, lipid oxidation and sensory property of chicken frankfurters during storage. AB - Broilers fed with three levels of fish oil (0, 2 and 4%) for 6 weeks were used in the manufacture of chicken frankfurters. The meat samples were vacuum-packed and stored at 0 degrees C for 0, 10, 20 and 30 days. Cooking yield, proximate and fatty acid composition, lipid oxidation, microbial and sensory properties of the meat products were measured. Cooking yield, moisture, fat, protein, ash and cholesterol contents of frankfurters were not affected (P>0.05) by levels of dietary fish oil. Frankfurters processed from chickens fed diets enriched with 2 and 4% of supplemental fish oil had a higher (P<0.05) level of n-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid), but had a lower level of n-6 fatty acids (P<0.05) than the controls (0% fish oil). TBA values and pH values of meat samples were not affected (P>0.05) by levels of supplemental fish oil in the diets, however, pH values of the vacuum-packaged chicken frankfurters decreased (P<0.05) as the storage time increased. No differences (P>0.05) in total anaerobic plate counts were observed among the fish oil treatments during storage. Supplementation of 2 and 4% fish oil in the diets did not increase (P>0.05) the intensity of fishy flavor in chicken frankfurters. PMID- 22063241 TI - Lipid composition, retention and oxidation in fresh and completely trimmed beef muscles as affected by common culinary practices. AB - The objective of this study was to determine how and to what extent several culinary practices (i.e. household cooking methods), each applied to the beef muscle deemed most suitable (boiling to infraspinatus, broiling to longissimus lumborum, oven-roasting and microwaving to semitendinosus), could induce significant changes in: lipid and cholesterol contents, fatty acid composition and contents, their true and apparent retention values, and some indices of lipid oxidation. Most nutrients increased their concentration as a consequence of moisture loss through cooking, whilst no substantial variation was induced in fatty acid composition. Nevertheless, each cooking method had its own distinctive heat processing parameters, which interacted with the characteristics peculiar to the pertaining muscle, leading to markedly different evaporative and drip losses, significantly different true retention values for cholesterol and the sum of polyunsaturated fatty acids, distinct responses as to lipid oxidation liability. The selected culinary practices seemed to be able to interact with the composition of the selected muscles, up to the point that pro-oxidant conditions were in some way counteracted by antioxidant effects. PMID- 22063242 TI - On attempts to measure the tenderness of Longissimus Dorsi muscles using fluorescence emission spectra. AB - Autofluorescence spectra have been obtained on beef longissimus dorsi muscles (n=151), and the spectra regressed against Warner-Bratzler (WB) peak values. The spectra obtained depended on the method used, and it is suggested that the difference is related to the use of two different types of Xenon lamps (a pulsed versus a continuous light source) and the inherent kinetic differences in the collection of the fluorochromes' emitted light. Poor to good (R=0.45-0.84) correlations between WB peak values and the emission spectra were obtained. This relationship is established using chemical information originating largely from collagens. Minor differences in predictability were observed using either excitation wavelengths 332 or 380 nm. The emission wavelengths containing the most relevant information about WB peak values were between 360 and 500 nm. Wavelengths around 375 nm, excitation 332 nm, were in particular important and were related to a component in the perimysial tissue, most likely being present in collagen I or III. Excitation at 380 nm revealed the wavelength range 460-480 nm as important presumed due to collagens in the perimysium. An experiment, simulating industrial routines, using 45 samples collected at the slaughterhouse two days post mortem, was carried out. However, for those samples no model was observed between the emission spectra and WB peak values. Only when some samples having very low (< 1.45 MUm) sarcomere lengths were removed, could a significant model be obtained. It is concluded that with the prevailing early post mortem routines in slaughterhouses with, among other things, wide variation in chilling rates between muscles and carcasses, the technique of autofluorescence has limited industrial potential as a sole, rapid non-destructive method for measuring tenderness of the longissimus dorsi muscle (LD). PMID- 22063243 TI - Electrical stunning of pigs: the effect of applied voltage on impedance to current flow and the operation of a fail-safe device. AB - The concept of a 'fail-safe' device to ensure that sufficient current is delivered to render a pig immediately unconscious when electrically stunned was investigated. For live pigs, no significant correlation could be determined between the pre-stun low voltage sensed impedance and the actual, higher voltage stun impedance. In contrast, a good correlation was found using heads from pigs killed more than 24 h previously. The impedance of a live pig's head was predominantly a function of the stunning voltage and decreased non-linearly with increasing voltage. The 'difference' between live and dead pigs was attributed to an 'ageing effect' which is not significant in the first few hours post mortem. No change in phase angle between corresponding stunning current and voltage waveforms, indicated that tissue reactance was not a contributing factor. It is concluded that 'fail-safe' devices based on low voltage pre-stun sensing are unlikely to meet the current legislative requirements (Council Directive 93/119/EC). PMID- 22063244 TI - Effect of dietary vitamin E and irradiation on lipid oxidation, color, and volatiles of fresh and previously frozen turkey breast patties. AB - Turkey breast meat patties, prepared from the turkeys fed diets containing 0, 50, 100, or 200 IU of dl-alpha-tocopheryl acetate (TA) per kg diet from 84 to 112 days of age, were aerobically packaged and irradiated at 0, 1.5, or 2.5 kGy. When dietary TA was increased from 0 to 200 IU/kg diet, plasma and muscle vitamin E levels increased by 5- and 4-fold, respectively. Dietary TA at 100 IU/kg diet significantly improved the storage stability of turkey breast, and it was more distinct in irradiated than nonirradiated meats. Both irradiation and dietary TA increased a*-values of turkey breast meat, but irradiation had a stronger impact. The redness of meat decreased during the 7-day storage, but irradiated meat maintained redder color than nonirradiated. Irradiated meat produced more sulfur volatiles and aldehydes than nonirradiated meats, and dietary TA effectively reduced these compounds during storage. The effects of dietary TA on the reduction of off-odor volatiles were more distinct in previously frozen-stored meats than in fresh meats. PMID- 22063245 TI - Comparison of acidic and alkaline catalysts for preparation of fatty acid methyl esters from ovine muscle with emphasis on conjugated linoleic acid. AB - Methanolic reagents containing acidic catalysts, HCl (0.5 M, 1 h, 80 degrees C) or BF(3) (14%, 1 h, 80 degrees C), or alkaline catalysts, KOH (0.2 M, 15-60 min, 50 degrees C) or NaOCH(3) (0.5 M, 15-60 min, 50 degrees C), were compared for use in preparation of fatty acid methyl esters for GC analysis of total lipids from freeze-dried semitendinosus muscle of lambs fed a 3.6% linoleate diet. Lipid preparations were in duplicate and included a total lipid extract, as well as direct transesterification and direct saponification of freeze-dried muscle. For the total lipid extracts, the weight% of 18:2 cis-9, trans-11 (CLA) with BF(3) (1.15) was 14.0% lower (P=0.001) than with either KOH (1.32) or NaOCH(3) (1.36); however, with HCl (1.25) CLA was intermediate (P=0.02). Concentrations of CLA (mg/g tissue) were similar (P ?0.44) within acidic or alkaline catalysts, but were 18.1% higher (P ?0.01) with KOH (2.56) and NaOCH(3) (2.52) than with HCl (2.01) or BF(3) (2.12). For direct transesterification, weight% of CLA was similar (P=0.55) with KOH (1.34) and NaOCH(3) (1.33), but each was 11.9% greater (P=0.003) than with HCl (1.18) and 19.1% greater (P=0.005) than with BF(3) (1.08). Concentrations of CLA after direct transesterification were greatest (P ?0.04) with KOH (3.31), followed by HCl (2.89, P=0.04), BF(3) (2.42, P ?0.004), and lowest (P ?0.002) with NaOCH(3) (2.21), indicating differences in efficiency of direct transesterification. Weight% of CLA in semitendinosus muscle, ranked highest to lowest, was lambs fed 3.6% linoleate (P ?0.003) > lambs fed 3.8% oleate (P ?0.01) > lambs fed a non-fat supplemented control diet (P ?0.01) when either BF(3) (saponified lipids) or KOH (direct transesterification) was used. Thus, dietary treatment effects on muscle CLA were not affected by catalyst. For the muscle of high-linoleate, high-oleate, and control lambs, CLA was 20.2, 13.9 and 0.0% higher, respectively, with KOH than BF(3), indicating that degradation of CLA by acidic catalysts decreased with lower starting amounts of CLA. PMID- 22063246 TI - Evaluation of sodium lactate as a replacement for conventional chemical preservatives in comminuted sausages inoculated with Listeria monocytogenes. AB - Sodium lactate (SL) as a potential replacer for potassium sorbate (PS) or sodium benzoate (SB) in comminuted sausages was evaluated. Sausages manufactured with 3.3% SL were compared with a control and 0.05 or 0.1% of PS and SB with regard to its influence on changes of chemical composition, physico-chemical and textural properties, and the growth of inoculated Listeria monocytogenes (LM) stored at 4 degrees C for up to 8 weeks. The sausages contained 62-64% moisture, 15-17% fat and 12-14% protein with pH range of 6.10-6.15 and water activity (a(w)) range of 0.936-0.941. Sausages containing 3.3% SL alone had lower (P<0.05) thiobarbituric acid reacting substances (TBARS) values than the control and those of PS (0.05 0.1%). Lightness values of sausages varied (P<0.05) among preservatives and storage times, while yellowness values tended to increase with storage time. Textural attributes (springiness and hardness) were reduced after 2 and 6 weeks storage, respectively. Sodium lactate at an incorporation level of 3.3% to sausage formulation had an antilisterial effect similar to those of 0.05-1.0% of PS or SB and delayed the lag phase for the growth of Listeria monocytogenes at least 2 weeks, compared with the control. PMID- 22063247 TI - Properties of restructured beef steaks from forage- and grain-fed cattle as affected by antioxidant and flavoring agents. AB - Beef trimmings from cattle finished on forage or grain were restructured into steaks to enhance palatability. Steaks were treated with propyl gallate with or without a beefy flavoring agent, stored at -29 degrees C, and analyzed after 0, 1, 3, and 6 months. The strong grassy flavor of forage-finished beef steaks, detected by a sensory panel, was masked by the beefy flavoring agent, rendering the beef more acceptable by consumers. Propyl gallate retarded lipid oxidation and rancidity development in steaks during extended frozen storage. Microbial populations decreased while color scores, cooking yield, and binding strength of steaks exhibited only minor changes during storage. Thus, the combination of antioxidant and flavoring agents with the muscle restructuring technology provides an effective means to enhance the palatability and storage stability of beef from forage-fed cattle. PMID- 22063248 TI - Utilization of pork collagen for functionality improvement of boneless cured ham manufactured from pale, soft, and exudative pork. AB - This study was designed to determine the effect of raw material and the inclusion of pork collagen on the protein functionality of boneless cured pork manufactured from 100% pale, soft, and exudative (PSE), 50% PSE, and 0% PSE with either 3 or 0% collagen. A Randomized Complete Block Design with six replications was utilized as the experimental design. Inclusion of collagen decreased (P<0.05) expressible moisture and increased (P<0.05) CIE b* value. Differences (P<0.05) revealed that collagen inclusion caused the 0% PSE treatments to have a lower cooking loss for 100% PSE treatments with and without collagen and a higher protein-protein bind value for 100% PSE treatments without collagen. Utilization of pork collagen in boneless cured pork that incorporates PSE meat increases water holding capacity and has the potential to improve protein functionality characteristics of the product. PMID- 22063249 TI - Meat quality in male fallow deer (Dama dama): effects of age and supplementary feeding. AB - Thirty-two male fallow deer, half 18- and half 30-month-old, were slaughtered after a 4-month feeding trial on pasture alone or with daily supplement of 500 g (dry matter) concentrate/head (eight each 18- and 30-month-old). Neither diet nor age produced significant effects on M. longissimus thoracis et lumborum (LM) and on M. semimembranosus (SM) pH and colour. Meat texture properties (Warner Bratzler-WB Shear Force and compression), water loss and collagen content were unaffected by diet, while the older deer had higher LM WB peak force values (4.15 vs 4.88 kg) and lower collagen solubility (34.61 vs 22.58%). LM and M. semitendinosus (ST) of the supplemented deer had a higher content of fat (pasture vs concentrate feeding: 0.56 vs 0.72% in LM; 0.55 vs 0.78% in ST) and provided lower PUFA, particularly n-3 PUFA, and higher n-6/n-3 ratio (3.30 vs 4.76 in LM; 3.39 vs 4.63 in ST). Thirty-month-olds' LM and ST were fatter than 18-month olds', and provided lower PUFA, both in the n-6 and n-3 fraction. PMID- 22063250 TI - Meat quality of designated South African indigenous goat and sheep breeds. AB - Carcass composition, proximate meat composition, fatty acid composition and sensory characteristics of two breeds of goats, Indigenous (n=12) and Boer goats (n=12), and two breeds of sheep, Damara (n=12) and Dorper (n=12), on extensive pasture-grazing, were analysed. The right side of each carcass was processed into wholesale cuts and dissected into subcutaneous fat, meat and bone. Meat and fat were minced together and sampled for proximate analysis as well as fatty acid profiles. The remaining minced meat was formed into meat patties, which were cooked for descriptive sensory evaluation of aroma, tenderness, juiciness and flavour characteristics by a trained panel. Goat and sheep breeds had different meat qualities. The composition and properties of subcutaneous and intramuscular fat contributed to the differences in meat quality observed within and between the species studied. Goats had proportionally smaller carcasses. Sheep yielded more dissectable fat and lean and less bone as a percentage of carcass weight than goat breeds, although the proportional lean content per cut of Boer goats was comparable to that of sheep. The percentage of bone was highest for Indigenous goats. Concentrations of saturated fatty acids were higher in goats compared to sheep. Sheep patties were more tender, juicy, greasy and less chewy compared to goat patties. The species related goaty and muttony flavour were clearly distinguishable. It is recommended that goats should be valued as a different species compared to sheep. PMID- 22063251 TI - Influence of dietary fat, on fatty acid composition and sensory properties of dry cured Parma ham. AB - A feeding trial with 27 pigs was performed in order to estimate the effect of different dietary fats on the fatty acid composition, flavour and sensory properties of dry-cured Parma hams, ripened for 16 months. The animals received a pelleted diet supplemented with different fat sources: tallow (TA), corn oil (CO), and rapeseed oil (RO). The sensory quality of the hams was evaluated by means of sensory analyses and by instrumental procedures such as gas chromatography-mass spectrometry of the volatile aroma compounds. A treatment effect was detected for linolenic acid in RO vs. CO and TA hams (P<0.01) and for MUFA content (P<0.01) that was higher in RO and TA compared with CO. The results of panel test showed a significant difference (P<0.05) between TA vs. CO and RO hams. Volatile compounds showed limited differences even if in CO group the amount of singular compound is higher than TA and RO. PMID- 22063252 TI - Early prediction of water-holding capacity in meat by multivariate vibrational spectroscopy. AB - This study had the dual purpose of (a) investigating the feasibility of measuring fundamental vibrational information in fresh porcine meat using infrared (IR) absorption and Raman scattering, and (b) investigating if the vibrational spectra obtained within 1 h after slaughter contained information about the water-holding capacity (WHC) of the meat. Preliminary studies performed at a research slaughterhouse revealed a high correlation between WHC and both IR (r=0.89) and Raman spectra using Partial Least Squares Regressions (PLSR). The good results were confirmed under industrial conditions using FT-IR at-line spectroscopy. However, the latter experiment yielded a somewhat lower correlation (r=0.79). This result is, however, promising for the purpose of finding a method for classification of carcasses with regard to WHC at the slaughter line. The IR region 1800-900 cm(-1) contains the best predictive information according to WHC of the porcine meat. This region covers functional group frequencies of water, protein, fat and glycogen, including the carbonyl and amide groups. PMID- 22063253 TI - Fatty acid composition of intramuscular lipids in various muscles of Holstein Friesian bulls slaughtered at different ages. AB - Holstein-Friesian bulls were slaughtered at 7, 14 and 19 months of age. Samples were collected from the psoas major, longissimus and semitendinosus muscles. The total lipids (TL) of the samples were extracted and the fatty acid compositions were analysed by gas chromatography. Both the slaughtering age and the type of muscles had significant effects on the intramuscular TL contents and fatty acid compositions. The longissimus muscle had higher intramuscular TL both at 14 and 19 months than at 7 months of age. As the bulls became older the proportion of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) increased in the TL of each muscle tested, whereas that of polyunsaturated fatty acids (PUFA) decreased. Among the muscle types, the semitendinosus had the lowest, intramuscular TL at each slaughtering age and the psoas major the highest. Except for SFA at 7 months of age, the semitendinosus showed lower levels of SFA and MUFA and higher proportions of PUFA than the other two muscles. PMID- 22063254 TI - Sensitive and semi-quantitative TaqManTM real-time polymerase chain reaction systems for the detection of beef (Bos taurus) and the detection of the family Mammalia in food and feed. AB - Consumers distrust beef or products that could contain beef because of the BSE (bovine spongiform encephalopathy) and vCJD (variant Creutzfeld Jacob Disease) cases during recent years. Cows could be fed with meat and bone meal-containing food. To regain consumer confidence methods are needed that allow the detection of smallest amounts of beef in the most different kind of products. Polymerase chain reaction (PCR) analysis can be used to detect the smallest amounts of even highly degraded DNA. In this work two methods are presented that allow the detection of mammal DNA and beef DNA, respectively, even in highly degraded DNA. The amplification of fragments as short as 66 and 76 bp, respectively, allow a determination of mammal or beef DNA even in meat and bone meal products. PMID- 22063255 TI - Evaluation of survival of Staphylococcus aureus and Clostridium botulinum in charqui meats. AB - Charqui meats were prepared in laboratory conditions in order to carry out experiments to observe the possibility of development of enterotoxigenic Staphylococcus aureus and Clostridium botulinum proteolytic type B spores and their toxins. Results demonstrated that the harsh processing conditions, high salt concentration, relative high temperature, a(w) values, inhibited the growth of both bacteria. Under our experimental conditions, S. aureus would survive throughout the sequence of salting steps i.e. brine followed by rock salting and the sunshine drying step. However, at final a(w) value of 0.70-0.75 would create conditions to inhibit its development. The other experiment revealed that C. botulinum spores germination also was impaired because of these low a(w) values. Under these conditions, charqui meats revealed to be safe products in relation to toxins from both enterotoxigenic S. aureus and C. botulinum. PMID- 22063256 TI - Effect of antimicrobial proteins from porcine leukocytes on Staphylococcus aureus and Escherichia coli in comminuted meats. AB - Study is aimed to elucidate the effect of porcine leukocyte antimicrobial protein on the proliferation of Staphylococcus aureus and Escherichia coli inoculated in ground meats. The antimicrobial proteins were isolated from porcine blood using 0.2 M sodium acetate extraction and cation-exchange column chromatography. Antimicrobial protein preparation consisted predominantly of 7.5 and 6 kDa molecules. Immunoblotting demonstrated that the 7.5 kDa molecule displayed defensin immuno-reactivity, a unique blood granulocyte antimicrobial protein. Both 7.5 and 6 kDa molecules could decrease apparent proliferation of test cultures. Sterilization (121 degrees C, 30 min) and proteolytic enzymes (pepsin, trypsin, and chymotrypsin) could significantly decrease bacteriocidal activities of antimicrobial protein preparation. Furthermore, antimicrobial protein preparation enhanced exposure of intercellular nucleotide of test cultures. Antimicrobial protein preparation inhibition of S. aureus and E. coli growth was concentration and time dependence. Adding 160 MUg/g antimicrobial protein preparation to ground ham meat and sausage mince could significantly (P<0.05) hurdle viable colony formation of test cultures at 6 and 12 h, respectively. Taken together, porcine leukocyte antimicrobial protein preparation has potential to inhibit proliferation of S. aureus and E. coli inoculated in ground meat via induction of bacterolysis, suggesting this antimicrobial protein preparation be an alternative natural bio-preservation source for ground meat products. PMID- 22063257 TI - Effect of crossbreeding and rearing system on sensory characteristics of Iberian ham. AB - The aim of this work was to study the influence of crossbreeding (Iberian and Iberian*Duroc 50% pigs) and rearing system (outdoors and indoors) on the sensory characteristics of Iberian ham [using descriptive analysis], and to investigate the relationships among sensory data and subcutaneous fat composition. Crossbreeding had a slight effect on sensory and fatty acid profile (only the bitter taste and some low-content fatty acids were significantly affected), but rearing system had a marked effect on subcutaneous fat composition (most fatty acids were affected) and sensory characteristics (texture characteristics being the most affected together with lean appearance and aroma). Palmitic, stearic and oleic acids were closely correlated to some sensory traits, not only lipid related characteristics (brightness, fat oiliness) but also to aroma. PMID- 22063258 TI - High temperature reduction of metmyoglobin in aqueous muscle extracts. AB - Oxymyoglobin in aqueous extracts of fresh beef longissimus dorsi muscles was initially oxidised to metmyoglobin during heat treatments at temperatures in the range 50-70 degrees C. The metmyoglobin then underwent reduction to a red pigment that was shown spectrally to be identical to oxymyoglobin. The formation of oxymyoglobin involved a heat induced precipitate that when removed from the solution, allowed oxidation to metmyoglobin to occur. However, on re-addition of the precipitate further reduction to oxymyoglobin took place. Dialysis of the muscle extract prior to heating markedly inhibited the reduction but addition of NADH to the dialysate permitted further reduction. The precipitate plus NADH caused oxymyoglobin formation in the presence of metmyoglobin but neither the precipitate nor NADH alone induced this formation. It is concluded that the initial conversion of oxymyoglobin to metmyoglobin on heating fresh beef muscle extracts was reversible and that the reverse reaction depended on the presence of both NADH and a muscle protein. PMID- 22063259 TI - Growth of carcass components and its relation with conformation in pigs of three types. AB - The growth of carcass tissues and developmental changes in tissue distribution were studied in three pig types which were selected to have morphologies that could be described as attenuated, blocky and flabby. These were achieved by incorporating, respectively, Landrace, Pietrain and Meishan genes to give commercial 'types' (designated L, P and M,) exhibiting some of the phenotypic qualities of these breeds. Twenty-five female pigs of each type with an average start weight of 27.2 kg were fed ad libitum and slaughtered over a (nominal) live weight range of 35-115 kg. Relations were quantified using the logarithmic transformation of data in the allometric model. Significant type differences in relative growth rates (the b coefficient or slope in the logarithmic plot) were not common, occurring in 14% of the relationships examined, whereas 61% of differences in the constant term (a or intercept in the logarithmic plot) were significant. Increase in carcass weight with age was not different between the types but in relation to slaughter live weight (dressing percentage) P had the highest value, M the lowest. Carcass dimensions showed that, relative to body length, P had the widest ham and shoulder over the whole size range whereas M had a deep (ventral-dorsal) shoulder and wide belly, attributes of shape that would be regarded as undesirable by the meat trade. Relative to carcass weight, L was only slightly longer (3 mm) in the body than M at the heavy end of the weight range but markedly longer (29 mm) than P. These differences in carcass conformation were also evident in the shape of pelvic limb muscles which, at a given length, were lightest and narrowest in M and, in some cases, heavier and wider in P than in L. Pelvic limb volume relative to limb length was greatest in P and least in M. Carcass composition (at a given prepared side weight) of P was characterized by low fat and high lean weights, and a high lean to bone ratio. Subcutaneous fat b was lowest in P, indicating that P was early maturing, but M carcasses had the most subcutaneous and intermuscular fat, also indicative of early maturing. There was, thus, no simple relation between maturity characteristics and carcass composition. M carcasses also had the greatest weight of skin. P had a light hindloin and heavy pelvic limb, M a heavy shoulder, hindloin and flank but a light pelvic limb; L had a light shoulder but a heavy foreloin. The distribution of individual tissues mirrored these differences in joint weights to a varying extent; in most cases the match (relatively heavy/light) was with a single tissue. These data, thus, indicated some pig type differences in tissue distribution and of particular significance was the relatively light lean mass in the pelvic limb of M. The results showed important differences in carcass quality between commercially available pig types differing in conformation. PMID- 22063260 TI - Sensory quality and the incidence of PSE of pork in relation to crossbreed and RN phenotype. AB - The effects of crossbreed and of RN phenotype on pork and its eating quality were evaluated in four different pig crossbreeds [involving Swedish Landrace (L) * Yorkshire (Y) sows and Hampshire (H), Duroc (D), Yorkshire (Y) or Hampshire * Yorkshire (HY) as the terminal sire]. Pigs from the LYH crossbreed were also classified as either carriers or non-carriers of the RN(-) allele. In the crossbreeds investigated, M. longissimus dorsi (LD) and M. semimembranosus (SM) from LYH were found to have the lowest pH as measured 24h post-mortem (pH(24h)). The low pH in the LYH crossbreed was due to the large proportion of RN(-) carriers it had (approximately 70%). The non-carriers of the RN(-) allele in the LYH crossbreed had a pH(24h) close to that of LYD, LYY and LYHY. In a selected group of pigs (N=50), the ultimate pH in the ham muscles M. biceps femoris (BF), M. quadriceps femoris (QF), M. gluteus medius (GM) and M. semitendinosus (ST) was also found to be lower in RN(-) carriers of LYH than in the other crossbreeds. As determined visually, LYD had the highest frequency (2%) of pale, soft and exudative meat (PSE), in LD. Ham from RN(-) carriers of LYH had the highest frequency (23%) of PSE meat around the femur, indicating that when the pH is low, the deep musculature, in which the chilling rate can be slow, is particularly sensitive to the development of PSE. According to assessments by members of a trained sensory panel, tenderness was significantly greater in LD from carriers of the RN(-) allele in LYH than in LD from LYD, LYHY and non-carriers of LYH. The tenderness of LD from LYY was rated as intermediate. The intramuscular fat content was found to be highest in LD from LYD, no relationship between intramuscular fat content and tenderness being found. The RN(-) carriers of LYH received the highest ratings in terms of juiciness. In conclusion, the sensory ratings demonstrated the great eating quality of LD from carriers of the RN(-) allele, indicating that abandoning the Hampshire crossbreed or eliminating the RN(-) allele from it, would result in the meat being less tender. PMID- 22063261 TI - Prediction of pork quality attributes from near infrared reflectance spectra. AB - Near infrared spectroscopy (NIRS) is one of the most promising techniques for large-scale meat quality evaluation. We investigated the potential of NIRS-based models to predict drip loss and shear force of pork samples. Near infrared reflectance spectra (1000-2500 nm), water-holding capacity, shear force, ultimate pH, and colour (L(*), a(*), b(*)-value) of 96 pork longissimus muscles were recorded at 2 days post mortem. Stepwise multiple linear regression (SMLR) and partial least squares regression (PLSR) analyses were used to formulate models for drip loss and shear force. Prediction models for drip loss correlated moderately strong with measured drip loss (R=0.71-0.74), which is similar to the correlation obtained using a combination of ultimate pH, filter paper test, and L(*)-value (R=0.74). The current results indicate that NIRS enables the classification of pork longissimus muscles with a superior or inferior water holding capacity as having a drip loss lower than 5% or higher than 7%. No useful models could be constructed for shear force. PMID- 22063262 TI - Meat nitrosamine contamination level depending on animal breeding factors. AB - The aim of the work was to answer the question how the species, breeding factors and season of the year affect nitrosamine contents in raw meat. The concentrations were assessed in raw pork from gilts, sows, hogs and boars, in beef from heifers, cows, bullocks and bulls, in veal and in horse, ram and goat meat. The studies were conducted in spring, summer, autumn and in winter. Meat contents of nitrosamines (dimethylonitrosamine-DMNA and diethylonitrosamine-DENA) were assessed by Pancholy's method adapted to nitrosamine determination in meat and meat products by Scanlan and Ryes. The levels of DMNA and DENA were determined using a Varian 3400 gas chromatograph coupled to a mass spectrometer (Finnigan MAT ITD. 800). The volatiles were identified by comparing their mass spectra with standards and by comparison of retention times with standards. Quantitative and qualitative analysis was conducted by comparison with N nitrosamine standard solution chromatograms. The highest nitrosamine (DMNA and DENA) concentrations were found in pork and beef, smaller in horseflesh and the lowest in ram and goat meat and in veal. PMID- 22063263 TI - Recent speciation and limited phylogeographic structure in Mixophyes frogs from the Australian Wet Tropics. AB - Through a combination of macroecological, paleoecological, and phylogeographical analyses, the rainforests of the Australian Wet Tropics (AWT) have emerged as a useful model for understanding sensitivity of species to past climatic change and, hence, for predicting vulnerability to future change. To extend the ecological breadth of comparative phylogeographic analyses, we investigate a clade of myobatrachid frogs, Mixophyes, a genus of large, stream-breeding but terrestrial frogs, three species of which are endemic to rainforests of the AWT. Here we (i) combine mtDNA, allozyme, and morphological data to refine knowledge of the geographic and environmental distribution of each taxon, (ii) resolve relationships among species, and (iii) use mtDNA phylogeography to infer responses of the three taxa to late-Pleistocene and Holocene climatic change. Each of the three species (Mixophyes carbinensis, Mixophyes coggeri, and Mixophyes schevilli) is effectively diagnosed by mtDNA, with the two small bodied, allopatric species (M. carbinensis and M. schevilli) being sister-taxa. Mixophyes have a very different history from other AWT amphibians, with more recent speciation (net divergences <5%) and much lower and geographically unstructured mtDNA diversity within each species. The combination of low diversity (theta(Pi)<0.36%) and strong signals of recent population expansion (Fu's Fs<0) suggests very high sensitivity to climate-driven rainforest dynamics, perhaps due to their large body size, low population density, and their requirement for both wet forest-floor litter and streams suitable for breeding. The results further emphasize the heterogeneity of species' responses to climate change and suggest that species dependent on multiple habitat types could be especially vulnerable. PMID- 22063264 TI - Next-generation sequencing reveals phylogeographic structure and a species tree for recent bird divergences. AB - Next generation sequencing (NGS) technologies are revolutionizing many biological disciplines but have been slow to take root in phylogeography. This is partly due to the difficulty of using NGS to sequence orthologous DNA fragments for many individuals at low cost. We explore cases of recent divergence in four phylogenetically diverse avian systems using a method for quick and cost effective generation of primary DNA sequence data using pyrosequencing. NGS data were processed using an analytical pipeline that reduces many reads into two called alleles per locus per individual. Using single nucleotide polymorphisms (SNPs) mined from the loci, we detected population differentiation in each of the four bird systems, including: a case of ecological speciation in rails (Rallus); a rapid postglacial radiation in the genus Junco; recent in situ speciation among hummingbirds (Trochilus) in Jamaica; and subspecies of white-crowned sparrows (Zonotrichia leucophrys) along the Pacific coast. The number of recovered loci aligning closely to chromosomal locations on the zebra finch (Taeniopygia guttata) genome was highly correlated to the size of the chromosome, suggesting that loci are randomly distributed throughout the genome. Using eight loci found in Zonotrichia and Junco lineages, we were also able to generate a species tree of these sparrow sister genera, demonstrating the potential of this method for generating data amenable to coalescent-based analysis. We discuss improvements that should enhance the method's utility for primary data generation. PMID- 22063265 TI - Association between acrochordons and the components of metabolic syndrome. AB - The aim of this study was to investigate the relationship between acrochordons and the components of metabolic syndrome (MS). A total of 192 patients with at least one skin tag and 104 controls having no skin tag seen at an academic outpatient dermatology clinic were involved. Body mass index (BMI), waist circumference, blood pressure, total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) values were measured. Oral glucose tolerance testing was performed. Patients with acrochordons were 64.6/35.4% female/male. The number of acrochordons was below 10 in 77.1% cases. The most frequent localization was the neck (72.4%). Acrochordons were smaller than 3 mm in 64.1% of the cases. Hypertension, diabetes and MS were significantly more frequent in patients with acrochordons than the control group. The acrochordon group showed significantly higher values of BMI, higher levels of TC, TG and LDL-C and significantly lower levels of HDL-C when compared with the control group. According to regression analysis, the number of acrochordons increased in patients with higher BMI values, 2-h plasma glucose, TC and LDL-C levels and lower HDL-C levels. These results support the suggestion that acrochordons are associated with the components of MS. PMID- 22063267 TI - Interaction of fast and slow dynamics in endocrine control systems with an application to beta-cell dynamics. AB - Endocrine dynamics spans a wide range of time scales, from rapid responses to physiological challenges to with slow responses that adapt the system to the demands placed on it. We outline a non-linear averaging procedure to extract the slower dynamics in a way that accounts properly for the non-linear dynamics of the faster time scale and is applicable to a hierarchy of more than two time scales, although we restrict our discussion to two scales for the sake of clarity. The procedure is exact if the slow time scale is infinitely slow (the dimensionless epsilon-quantity is the period of the fast time scale fluctuation times an upper bound to the slow time scale rate of change). However, even for an imperfect separation of time scales we find that this construction provides an excellent approximation for the slow-time dynamics at considerably reduced computational cost. Besides the computation advantage, the averaged equation provided a qualitative insight into the interaction of the time scales. We demonstrate the procedure and its advantages by applying the theory to the model described by Tolic et al. [I.M. Tolic, E. Mosekilde, J. Sturis, Modeling the insulin-glucose feedback system: the significance of pulsatile insulin secretion, J. Theor. Biol. 207 (2000) 361-375.] for ultradian dynamics of the glucose insulin homeostasis feedback system, extended to include beta-cell dynamics. We find that the dynamics of the beta-cell mass are dependent not only on the glycemic load (amount of glucose administered to the system), but also on the way this load is applied (i.e. three meals daily versus constant infusion), effects that are lost in the inappropriate methods used by the earlier authors. Furthermore, we find that the loss of the protection against apoptosis conferred by insulin that occurs at elevated levels of insulin has a functional role in keeping the beta-cell mass in check without compromising regulatory function. We also find that replenishment of beta-cells from a rapidly proliferating pool of cells, as opposed to the slow turn-over which characterises fully differentiated beta-cells, is essential to the prevention of type 1 diabetes. PMID- 22063268 TI - A comprehensive evaluation of a diabetes quality improvement project in privately owned primary care practices that serve minority patients. AB - The authors conducted a diabetes quality improvement project in 5 privately owned primary care practices serving at least 25% minority patients. Interventions included group-specific and practice-specific training on an electronic patient registry, cultural competency practices and tools, and selected quality improvement strategies. The authors conducted a comprehensive evaluation involving quantitative and qualitative data to assess project impact. Although overall clinical performance did not improve over the 14- to 20-month project time frame, other practice structural characteristics and processes did show improvement: successful implementation of the registry and clinician reminders in all practices, institution of team care and patient reminders in 4 practices, and collection of patient race/ethnicity data in 4 practices. These results highlight the difficulty of bringing about clinical improvement in this subset of practices and also the importance of conducting comprehensive evaluations to fully understand and interpret multicomponent quality improvement projects. PMID- 22063269 TI - Regulation of triglyceride metabolism by Angiopoietin-like proteins. AB - Plasma triglyceride concentrations are determined by the balance between production of the triglyceride-rich lipoproteins VLDL and chylomicrons in liver and intestine, and their lipoprotein lipase-mediated clearance in peripheral tissues. In the last decade, the group of Angiopoietin-like proteins has emerged as important regulators of circulating triglyceride (TG) levels. Specifically, ANGPTL3 and ANGPTL4 impair TG clearance by inhibiting lipoprotein lipase (LPL). Whereas ANGPTL4 irreversibly inactivates LPL by promoting conversion of active LPL dimers into inactive monomers, ANGPTL3 reversibly inhibits LPL activity. Studies using transgenic or knockout mice have clearly demonstrated the stimulatory effect of Angptl3 and Angptl4 on plasma TG, which is further supported by human genetic data including genome wide association studies. Whereas ANGPTL3 is mainly active in the fed state, ANGPTL4 is elevated by fasting and mediates fasting-induced changes in plasma TG and free fatty acid metabolism. Both proteins undergo oligomerization and are subject to proteolytic cleavage to generate N- and C-terminal fragments with highly divergent biological activities. Expression of ANGPTL3 is exclusive to liver and governed by the liver X receptor (LXR). In contrast, ANGPTL4 is expressed ubiquitously and under sensitive control of the Peroxisome proliferator-activated receptor (PPAR) family and fatty acids. Induction of ANGPTL4 gene expression by fatty acids and via PPARs is part of a feedback mechanism aimed at protecting cells against lipotoxicity. So far there is very little evidence that other ANGPTLs directly impact plasma lipoprotein metabolism. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID- 22063270 TI - Endoplasmic reticulum stress-mediated inhibition of NSMase2 elevates plasma membrane cholesterol and attenuates NO production in endothelial cells. AB - Chronic exposure of blood vessels to cardiovascular risk factors such as free fatty acids, LDL-cholesterol, homocysteine and hyperglycemia can give rise to endothelial dysfunction, partially due to decreased synthesis and bioavailability of nitric oxide (NO). Many of these same risk factors have been shown to induce endoplasmic reticulum (ER) stress in endothelial cells. The objective of this study was to examine the mechanisms responsible for endothelial dysfunction mediated by ER stress. ER stress elevated both intracellular and plasma membrane (PM) cholesterols in BAEC by ~3-fold, indicated by epifluorescence and cholesterol oxidase methods. Increases in cholesterol levels inversely correlated with neutral sphingomyelinase 2 (NSMase2) activity, endothelial nitric oxide synthase (eNOS) phospho-activation and NO-production. To confirm that ER stress induced effects on PM cholesterol were a direct consequence of decreased NSMase2 activity, enzyme expression was either enhanced or knocked down in BAEC. NSMase2 over-expression did not significantly affect cholesterol levels or NO-production, but increased eNOS phosphorylation by ~1.7-fold. Molecular knock down of NSMase2 decreased eNOS phosphorylation and NO-production by 50% and 40%, respectively while increasing PM cholesterol by 1.7-fold and intracellular cholesterol by 2.7 fold. Furthermore, over-expression of NSMase2 in ER-stressed BAEC lowered cholesterol levels to within control levels as well as nearly doubled the NO production, restoring it to ~74% and 68% of controls using tunicamycin and palmitate, respectively. This study establishes NSMase2 as a pivotal enzyme in the onset of endothelial ER stress-mediated vascular dysfunction as its inactivation leads to the attenuation of NO production and the elevation of cellular cholesterol. PMID- 22063271 TI - Distinct cellular pools of perilipin 5 point to roles in lipid trafficking. AB - The PAT family of lipid storage droplet proteins comprised five members, each of which has become an established regulator of cellular neutral lipid metabolism. Perilipin 5 (also known as lsdp-5, MLDP, PAT-1, and OXPAT), the most recently discovered member of the family, has been shown to localize to two distinct intracellular pools: the lipid storage droplet (LD), and a poorly characterized cytosolic fraction. We have characterized the denser of these intracellular pools and find that a population of perilipin 5 not associated with large LDs resides in complexes with a discrete density (~1.15 g/ml) and size (~575 kDa). Using immunofluorescence, western blotting of isolated sucrose density fractions, native gradient gel electrophoresis, and co-immunoprecipitation, we have shown that these small (~15 nm), perilipin 5-encoated structures do not contain the PAT protein perilipin 2 (ADRP), but do contain perilipin 3 and several other as of yet uncharacterized proteins. The size and density of these particles as well as their susceptibility to degradation by lipases suggest that like larger LDs, they have a neutral lipid rich core. When treated with oleic acid to promote neutral lipid deposition, cells ectopically expressing perilipin 5 experienced a reorganization of LDs in the cell, resulting in fewer, larger droplets at the expense of smaller ones. Collectively, these data demonstrate that a portion of cytosolic perilipin 5 resides in high density lipid droplet complexes that participate in cellular neutral lipid accumulation. PMID- 22063272 TI - Lipase maturation factor 1: a lipase chaperone involved in lipid metabolism. AB - Mutations in lipase maturation factor 1 (LMF1) are associated with severe hypertriglyceridemia in mice and human subjects. The underlying cause is impaired lipid clearance due to lipase deficiency. LMF1 is a chaperone of the endoplasmic reticulum (ER) and it is critically required for the post-translational activation of three vascular lipases: lipoprotein lipase (LPL), hepatic lipase (HL) and endothelial lipase (EL). As LMF1 is only required for the maturation of homodimeric, but not monomeric, lipases, it is likely involved in the assembly of inactive lipase subunits into active enzymes and/or the stabilization of active dimers. Herein, we provide an overview of current understanding of LMF1 function and propose that it may play a regulatory role in lipase activation and lipid metabolism. Further studies will be required to test this hypothesis and elucidate the full spectrum of phenotypes in combined lipase deficiency. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID- 22063273 TI - Rotational and hinge dynamics of discoidal high density lipoproteins probed by interchain disulfide bond formation. AB - To develop a detailed double belt model for discoidal HDL, we previously scored inter-helical salt bridges between all possible registries of two stacked antiparallel amphipathic helical rings of apolipoprotein (apo) A-I. The top score was the antiparallel apposition of helix 5 with 5 followed closely by appositions of helix 5 with 4 and helix 5 with 6. The rationale for the current study is that, for each of the optimal scores, a pair of identical residues can be identified in juxtaposition directly on the contact edge between the two antiparallel helical belts of apoA-I. Further, these residues are always in the '9th position' in one of the eighteen 11-mer repeats that make up the lipid associating domain of apoA-I. To illustrate our terminology, 129j (LL5/5) refers to the juxtaposition of the Calpha atoms of G129 (in a '9th position') in the pairwise helix 5 domains. We reasoned that if identical residues in the double belt juxtapositions were mutated to a cysteine and kept under reducing conditions during disc formation, we would have a precise method for determining registration in discoidal HDL by formation of a disulfide-linked apoA-I homodimer. Using this approach, we conclude that 129j (LL5/5) is the major rotamer orientation for double belt HDL and propose that the small ubiquitous gap between the pairwise helix 5 portions of the double belt in larger HDL discoidal particles is significantly dynamic to hinge off the disc edge under certain conditions, e.g., in smaller particles or perhaps following binding of the enzyme LCAT. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010). PMID- 22063274 TI - Effects of crossbreeding Mexican Pelibuey sheep with Rambouillet and Suffolk on carcass traits. AB - Fifty nine lambs: Pelibuey (P), Suffolk*Pelibuey (SP) and Rambouillet*Pelibuey (RP), were used to evaluate the effect of crossbreeding on carcass characteristics and composition. Following carcass evaluation, muscle, bone, subcutaneous, seam, internal, total fat and other tissues were dissected. Carcass dressing percentage was similar across the three genotypes. The genetic group did not influence the percentage of cuts, except for shoulder percentage. Pelibuey carcasses had less fat thickness than RP and more kidney, pelvic and heart fat than SP. Muscle percentage was lower for RP (51.27+/-0.68) compared to P (54.01+/ 0.61) and SP (53.78+/-0.58) carcasses, respectively. Consequently, the RP group showed the highest proportion of total fat (19.66+/-1.00). In general, RP carcasses had the lowest meat cutability. In conclusion, carcass yield of Pelibuey lambs was not improved by the cross with either Rambouillet or Suffolk breeds. PMID- 22063275 TI - Growth, carcass and meat characteristics of Karayaka growing rams fed sugar beet pulp, partially substituting for grass hay as forage. AB - Twenty-one growing male Karayaka sheep were divided into three groups of seven at 12 months of age. All groups received a commercial feed (60%) and roughage (40%). One group received grass hay as roughage (control, C), the other two groups received a mixture in which 40 (0.40SBP) or 60% (0.60SBP) sugar beet pulp (SBP) was used in partial replacement of grass hay in the C group during 56 days. Dry matter (DM) intake and DM conversion index (kg DM per kg weight gain) of the C group were higher (P<0.01) than that of the 0.40SBP and 0.60SBP groups. While the 0.60SBP increased (P<0.05) the L* of meat from the Karayaka young rams, the 0.40SBP or 0.60SBP decreased the ultimate pH (P<0.05) and cooking loss (P<0.01) compared to the C group. Means for redness (a*), yellowness (b*), Hue (H*) and Chroma (C*) and sensory characteristics indicated that there were no significant differences between dietary treatments. Inclusion of 60% SBP increased the palmitic (P<0.02) and linoleic (P<0.01) acid contents of the meat, it decreased (P<0.01) stearic, oleic and arachidonic acid contents compared to the C group. The 0.40SBP also increased (P<0.01) the linoleic acid content of the meat, but it decreased (P<0.01) stearic and arachidonic acid contents compared to the control. Although meat from young rams fed 0.60SBP diet had a higher value of lightness and linoleic acid, and a lower value of cooking loss than those from animals fed the C diet, sensory evaluation did not discriminate the meat from young rams fed with control and/or SBP diets. Therefore, grass hay can be replaced by 60% of SBP in the growing diet for Karayaka rams without a reduction in meat quality. PMID- 22063276 TI - Concentrations of oxysterols in meat and meat products from pigs fed diets differing in the type of fat (palm oil or soybean oil) and vitamin E concentrations. AB - The aim of this study was to find out whether concentrations of oxysterols in pig meat are affected by dietary polyunsaturated fatty acids and vitamin E. 48 growth finishing pigs were fed diets with either palm oil or soybean oil and vitamin E concentrations of 15, 40 or 200 mg/kg. Concentrations of oxysterols were analyzed in fresh and heat-processed (180 degrees C, 20 min) meat (M. longissimus dorsi) and in boiled sausage prepared from meat and back fat of the animals. Concentrations of oxysterols in fresh muscle were below 5 nmol/g dry matter; they were independent of the dietary fat type and vitamin E concentration. Heating caused a large increase of oxysterol concentration (up to 55 nmol/g dry matter). This effect was reduced by increasing dietary vitamin E concentration but was independent of the dietary fat. Sausage from pigs fed soybean oil had higher concentrations of oxysterols than sausage from pigs fed palm oil; vitamin E reduced concentrations of oxysterols in sausage from pigs fed soybean oil, but not in sausage from pigs fed palm oil. PMID- 22063277 TI - Antioxidant properties of selected Oriental non-culinary/nutraceutical herb extracts as evaluated in raw and cooked meat. AB - Ethanol extracts of white peony (WP), red peony (RP), sappanwood (SW), Moutan peony (MP), rehmania (RE) or angelica (AN) were individually added to ground goat meat at 0.5-2.0% (g dry extract/100 g final meat sample), and raw and cooked samples were aerobically refrigerated for 0, 3 or 6 days. These extracts and rosemary extract (RO) were also individually added to salted or unsalted ground beef at 0.01-0.25% and refrigerated as raw or cooked patties. WP, RP, RE, SW and MP markedly reduced (P<0.05) lipid oxidation in cooked-stored goat meat. With 0.25% of WP, RP, SW, MP or RO in beef, lipid oxidation during storage was minimal in raw and cooked patties (plain or salted); raw patty redness values at day 6 were higher (P<0.05) for SW, WP, RP or MP than RO treatment or the control. At 0.01%, SW was more antioxidative (P<0.05) than the other extracts. PMID- 22063278 TI - Influence of pasture or grain-based diets supplemented with vitamin E on antioxidant/oxidative balance of Argentine beef. AB - Argentine meat has been traditionally produced on pasture. However, to comply with some market requirements, grain finishing is becoming more common among producers. The main goal of the present work was to study lipid oxidation in fresh meat from animals fed different diets in relationship with their antioxidant vitamin status. Attributes were evaluated in beef from pasture or grain-fed animals with (PE and GE) or without supplementation (P and G) with vitamin E (500 UI/head/day). Fresh meat produced on grain (G and GE) had higher fat (4.0+/-1.6 and 4.7+/-1.4 g/100 g) and cholesterol content (51.0+/-3.0 and 52.0+/-4.0 mg/100 g) than meat from pasture (P and PE) fed animals (2.7+/-1.2 to 2.9+/-1.1 g/100 g and 48.0+/-5.0 to 49.0+/-4.0 mg/100 g of intramuscular fat and cholesterol respectively). Fatty acid composition was clearly affected by diet. Beef from pasture-fed cattle had higher percentage of linolenic acid, less linoleic acid and, overall, higher percentage of polyunsaturated fatty acids than beef from grain-fed animals (P<0.05). Thiobarbituric acid reactive substances number and volatile levels of hexanal, pentanal, heptanal, octanal and 3 methylbutanal were higher in grain than in pasture samples (P<0.05). P+PE meat had higher content of antioxidant vitamins than G+GE samples (P<0.001). Values ranged from: 15.92+/-3.48 (G) to 17.39+/-4.29 (GE) and 25.3+/-10.0 (P) to 21.98+/ 5.11 (PE) MUg/g of ascorbic acid; from 1.05+/-0.73 (G) to 1.76+/-0.97 (GE) and 3.08+/-0.45 to 3.91+/-0.74 MUg/g of alpha-tocopherol; and from 0.06+/-0.03 (G) to 0.05+/-0.01 (GE) and 0.45+/-0.21 (P) to 0.63+/-0.27 (PE) MUg/g of beta-carotene. In addition, principal component analysis clearly separated grain from pasture samples regardless of their supplementation with vitamin E. This level of supplementation did not improve the antioxidant status of fresh meat (P>0.05). We conclude that pasture diet contributes natural antioxidants in sufficient amounts and is an efficient way to prevent lipid oxidation in fresh beef. PMID- 22063279 TI - The effect of dietary fish oil rich in n-3 fatty acids on the organoleptic, fatty acid and physicochemical characteristics of ostrich meat. AB - The effect of different levels of unrefined fish oil in the diet on ostrich Musculus iliofibularis was evaluated in a completely randomised experimental design, where a supplementary energy rich feed, containing 6.7% fish oil, was fed at four different levels over a 7-month period. An increase in the amount of fish oil consumed was found to have had no significant effect on the sensory characteristics of ostrich meat, although there was a tendency towards an increase in fishiness, for both aroma and flavour. Increased concentrations of fish oil, however, did have a significant effect on the aroma and flavour of the abdominal fat pads. The muscle pH(f) and muscle lightness (L*) revealed a significant reduction, with increased energy intake. However, the increased energy intake had no effect on the chemical composition (moisture, protein, fat, and ash content) of the meat. The fatty acid profile of both adipose tissue and muscle was altered as a result of the consumption of fish oil. The SFA concentration increased, while the PUFA concentration decreased with increasing dietary levels. The MUFA concentration remained constant for all four groups. PMID- 22063280 TI - Changes in calpain and calpastatin activities of osmotically dehydrated bovine muscle during storage after treatment with calcium. AB - Calpain and calpastatin activities were investigated in calcium-treated beef after osmotic dehydration. Dehydrated beef was soaked in 150 mM calcium chloride solution for 3 h, and then stored for 48 h at 3-4 degrees C. The untreated sample (control) was soaked in deionized water for 3 h instead of calcium chloride solution, after osmotic dehydration. The increase and decrease in the relative activity of crude calpain were observed in the untreated and the calcium treated meat, respectively, during the storage. When the crude calpains were subjected to DEAE-Sephacel column chromatography, it was found that MU-calpain activity decreased rapidly during the storage in the untreated meat, whereas there was almost no change in the activity of m-calpain during the storage. The decrease of calpastatin activity was moderate compared with the decrease of MU calpain activity. In the calcium chloride-treated meat, however, no MU-calpain nor calpastatin activities was detectable after 48 h at cold-room temperature, and m-calpain activity after 48 h had decreased to 6.1% of its activity immediately after thawing. It was concluded that 150 mM calcium chloride treatment after osmotic dehydration was sufficient to introduce calcium ions into the meat. In the presence of sufficient calcium, autolysis of calpains and proteolytic degradation of calpastatin, which eventually related to the rate of decrease in calpain and calpastatin activities, clearly seem to be related to a decrease in meat toughness. PMID- 22063281 TI - Effects of dietary olive and linseed oil on lipid composition, meat quality, sensory characteristics and muscle structure in pigs. AB - The aim of this study was to alter the fatty acid composition of porcine tissue by accumulating essential fatty acids without adversely affecting carcass composition, muscle structure or meat eating quality. A total of 13 female and 12 castrated Pietrain*German Landrace pigs were fed a basal concentrate diet supplemented with 5% olive oil or 5% linseed oil during the growing-finishing period. Carcass composition and meat quality were not affected by the diet. Feeding linseed oil to pigs significantly increased the relative content of linolenic acid and long chain n-3 fatty acids in lipids of muscle, backfat and heart at the expense of arachidonic acid. Oleic acid was accumulated in muscle, backfat and heart lipids by feeding olive oil. The overall flavour of combined meat/backfat samples from castrates was negatively influenced by linseed oil supplementation compared to supplementation with olive oil. The oxidative stability of muscle lipids was lower in linseed oil-fed pigs compared to olive oil fed pigs. The greater cross section areas of the longissimus muscle of females were caused by an increased diameter of red, intermediate and white fibres. PMID- 22063282 TI - Elucidation of the relationship between cooking temperature, water distribution and sensory attributes of pork - a combined NMR and sensory study. AB - Low-field NMR T(2) relaxation was measured continuously during cooking of pork samples (m. longissimus dorsi) to a final temperature of 75 degrees C. Simultaneously the remaining muscle was cooked in an oven to a core temperature of either 62 or 75 degrees C and subsequently evaluated by a sensory panel. Highly significant effects of final cooking temperature on the sensory attributes juiciness (initial and final), hardness, tenderness, crumbliness and chewing time were found. Juiciness and tenderness decreased with increasing temperature, while hardness, crumbliness and chewing time increased with increasing temperature. Distributed T(2) relaxation data revealed marked effects of temperature (62 vs. 75 degrees C) on the water distribution within the meat. Partial least squares (PLS) regressions were used to examine a potential prediction of sensory attributes from the distributed T(2) relaxation data, and high correlations were obtained. Moreover, loadings from the PLS regressions were analysed to evaluate the alterations in the water distribution as a function of temperature that contribute to changes in juiciness. This analysis revealed that the reduction in juiciness at 75 degrees C can be ascribed to changes in the size of the pores confining the myofibrillar water together with an expulsion of water. PMID- 22063283 TI - Effect of weight at slaughter on the volatile compounds of cooked beef from Spanish cattle breeds. AB - The volatile compounds in cooked beef from the local Spanish cattle breeds, Asturiana, Avilena, Parda Alpina, Pirenaica, Retinta, Rubia Gallega, and Morucha, were studied. Bulls were slaughtered at a live weight of 300 and 550kg and the beef was aged for seven days before cooking. Differences in volatile composition among the breeds were considerable and may contribute to the perception of flavour differences in the cooked beef. Peak area values for dimethyl sulfide, which could be related to cauliflower notes, were highest for the meat from the Pirenaica breed. Levels of the detected volatiles, especially sulfur compounds, in the beef from the Asturiana breed were low-intermediate and were potentially related to blood and liver notes and unpleasant flavours. Avilena stood out among the rustic breeds because of its high values for 1-octene, methylcyclohexane, tetradecane and carbon disulfide, while Retinta displayed high 2,3,4 trimethylpentane levels. The effect of weight at slaughter was influenced by breed, because, except for octane, all the volatile compounds behaved differently according to the breed. Ethanol was characteristic of animals with a high percentage intramuscular fat content, and carbon disulfide was characteristic of animals slaughtered at the lower of the two live weights considered. PMID- 22063284 TI - Benchmarking value in the pork supply chain: Processing and consumer characteristics of hams manufactured from different quality raw materials. AB - Impact of fresh ham quality on finished ham product characteristics was evaluated. Bone-in hams destined for spiral-sliced ham manufacturing were sorted into two pH groups before processing: pH?5.5 and pH?5.6. For boneless hams, raw materials were sorted into groups with different levels of pale, soft, and exudative (PSE) product before manufacturing into sliced vacuum packaged hams: "Low PSE" (?5% PSE muscle), "Intermediate PSE" (20-30% PSE muscle) or "High PSE" (40-60% PSE muscle). Few differences were observed between the pH?5.5 and pH?5.6 groups in objective color measures and drip loss in bone-in spiral-sliced hams stored under refrigeration, however, after frozen storage, hams from the pH?5.5 group had lower L*- and a*-values and had much higher drip loss than those from the pH?5.6 group. Processing yields for bone-in spiral-sliced hams were similar through cooking and chilling, however, the pH?5.6 group had higher yields after slicing. For boneless hams, defects occurred at a greater frequency in hams formulated with a greater percentage of PSE raw materials than those with lower amounts of PSE. Differences in objective color measures and purge were minimal over the duration of storage time, but hams formulated with greater percentages of PSE raw materials were lighter in appearance and had less redness. Consumers gave lower color responses for hams formulated with "High PSE" amounts, but did not differentiate between hams manufactured with lower quantities of PSE muscle. However, when consumers directly compared packages of ham, there was distinct discrimination against hams manufactured with greater amounts of PSE. Purchase intent showed that consumers favored ham manufactured from fresh ham muscles containing low quantities of PSE tissue. Further research is needed to determine the optimal ratio of allowable PSE product in formulation that enables processors to maximize consumer appeal with the economic realities of sorting out PSE pork. PMID- 22063285 TI - Quality of low-fat meatballs containing Legume flours as extenders. AB - Meatballs were extended with blackeye bean flour (BBF), chickpea flour (CF), lentil flour (LF) and rusk (R) at level of 10%. Raw and cooked meatballs were analyzed for moisture, fat, protein and ash content. Cooking properties and colour parameters were evaluated. BBF and LF resulted in greater cooking yield, fat retention and moisture retention values. Meatballs extended with LF were lighter than other samples. Meatballs formulated with BBF had the lowest reduction in diameter. Meatballs with BBF and CF had higher water holding capacity (WHC) than other treatment groups. All meatballs incorporating legume flours were tougher (lower penetration values) than the R treatment. According to sensory evaluation results all meatball treatments had high acceptability and received high scores (6.8 and above). Meatballs with BBF and CF had lower TBA values than meatballs with LF and R at 3rd month of frozen storage at -18 degrees C. PMID- 22063286 TI - Meat species identification by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of mitochondrial 12S rRNA gene. AB - Adulteration of high quality meat and meat products with their inferior/cheaper counterparts is a problem in the meat industry. The present study investigated the use of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of the mitochondrial 12S rRNA gene for identification of the origin of meats. PCR-RFLP was applied for species identification of beef, buffalo meat, mutton and chevon. PCR amplification yielded a 456-bp fragment in each of these species. The amplicons were digested with AluI, HhaI, ApoI and BspTI restriction enzymes resulting in a pattern that could identify and differentiate each of the above species. This technique did not yield satisfactory results with meat mixtures/meats. However, consistent results were obtained with both fresh and processed meat samples. PMID- 22063287 TI - TaqMan real-time PCR for the detection and quantitation of pork in meat mixtures. AB - A rapid and highly specific real-time quantitative PCR, based on the amplification of a fragment of the mitochondrial 12S ribosomal RNA gene (rRNA), has been developed for the quantitation of pork (Sus scrofa) in binary pork/beef muscle mixtures. The method combines the use of pork-specific primers, that amplify a 411bp fragment from pork DNA, and mammalian-specific primers amplifying a 425-428bp fragment from mammalian species DNA, which are used as endogenous control. An internal fluorogenic probe (TaqMan), that hybridizes in the "pork specific" and also in the "mammalian" DNA fragments is used to monitor the amplification of the target gene. A comparison of the cycle number (C(t)) at which mammalian and pork-specific PCR products are first detected, in combination with the use of reference standards of known pork content, allows the determination of the percentage of pork in a mixed sample. Analysis of experimental pork/beef muscle binary mixtures demonstrated the specificity and sensitivity of the assay for detection and quantitation of pork in the range 0.5 5%. PMID- 22063288 TI - Benchmarking value in the pork supply chain: Processing characteristics and consumer evaluations of pork bellies of different thicknesses when manufactured into bacon. AB - Impact of belly thickness on processing yields and consumer evaluations of finished bacon products was measured. Before processing through a commercial facility, pork bellies (n=96 per group) were sorted into three target thickness groups: "thin" (approximately 2.0cm); "average" (approximately 2.5cm); "thick" (approximately 3.0cm). Processing yields at various production points were recorded and samples from each thickness group were evaluated by consumers for palatability characteristics and visual appearance. Bacon manufactured using "thick" bellies had the highest processing yields through the smoking and cooking phase. "Thin" bellies had the lowest slicing yields and generated the highest percentage of less valuable "#2 slices" (slice profile less than 1.9cm at any point) and "ends and pieces." Consumers found that bacon manufactured from "average" thickness bellies did not have deficiencies in palatability characteristics, but bacon manufactured from "thin" bellies lacked crispiness and bacon manufactured from "thick" bellies lacked flavor. Consumers found the lean to-fat ratio and the visual appearance of bacon from "thick" bellies was less appealing than bacon from "thin" and "thick" bellies. Moreover, consumers showed much stronger purchase intent for bacon from "thin" and "average" bellies. Belly thickness impacted processing yield and consumer palatability evaluations of bacon. Producers need to minimize production of "thin" bellies because of reduced processing yields and "thick" bellies because of reduced consumer appeal. PMID- 22063289 TI - Effects of pH adjustment with phosphates on attributes and functionalities of normal and high pH beef. AB - Longissimus dorsi muscles from six normal- and six high-ultimate pH bulls were selected for fine mincing and subsequent pH adjustment with acid and alkaline pyrophosphate. Four pH treatments were prepared: initially high remains high (mean of pH 6.37), high becomes normal (5.62); initially normal remains normal (5.65), and normal becomes high (6.21). The addition level of phosphate as P(2)O(5) was the same in all replicates. Before pH adjustment, colour and water holding capacity (WHC) values were strongly affected by higher (initial) pH in expected ways: darker, lower chroma, higher capacity. After pH adjustment, these values were affected only by the final pH, not the initial pH (the pH history). Total protein solubility was likewise affected by final pH but not initial pH. In contrast, the combination high initial pH-high final pH improved sarcoplasmic protein solubility by 20% over the combination normal initial pH-high final pH. Sarcoplasmic protein solubility is an indicator of strain required to fracture cooked batters made from the minced meats; in the event, the rank order of the four treatments for strain-to-fracture matched that of sarcoplasmic protein solubility. Statistically, sarcoplasmic protein solubility and strain-to-fracture were both affected by initial pH (P<0.01) and final pH (P<0.001). However, stress required to fracture cooked batters was entirely controlled by initial pH (P<0.01). In other words, the stress-to-fracture advantage of initially high pH meat was not matched by upward pH adjustment of initially normal pH meat. Emulsion stability, which is better with higher pH meat, was affected by initial and final pH (both P<0.01). Cook yield, like WHC of pH-adjusted raw meat, was more due to final pH than initial pH, similarly cooked batter colour, whereas final pH had a significant effect on quality attributes (generally better when higher). An initially high pH history conferred an enduring advantage on three important batter attributes, stress-to-fracture, strain-to-fracture, and emulsion stability. Therefore, prior exposure of beef to normal pH conditions (pH 5.4-5.7) renders it less useful as a manufacturing grade product. PMID- 22063290 TI - Carcass characteristics and meat quality of male and female foals. AB - This research was conducted to characterize the carcass traits and meat quality of 16-month and 24-month old foals (33 males and 23 females) reared in two different livestock production systems. The carcass parameters assessed were conformation, degree of fatness, morphology, weight and carcass meat colour. The physicochemical characteristics and sensory profile of the M. longissimus dorsi (LD) were determined at 4 days of ageing. The carcass parameters and meat quality traits differed little between colts and fillies. There were significant differences between production systems. Carcasses were characterized by B conformation, 3 of fatness and high dressing percentages (>63%). Foal meat had a high myoglobin content and there were differences between the production systems in the flavour, juiciness, flourness and greasiness of the LD. PMID- 22063291 TI - Quality of ham pate containing bovine globin and plasma as fat replacers. AB - The effect of the incorporation of globin (10%), plasma (10%) and both combined (5% each) as fat replacers on the quality of ham pate was investigated. The chemical composition, the sensorial analysis (color, flavor and consistency) and the instrumental analysis of the texture (hardness, adhesiveness, elasticity, cohesiveness and tackiness) were evaluated. The results showed an increase of moisture and protein contents after the fat replacement, while the fat reduction of 25-35% led to the preparation of light products. No change was observed for the aroma, taste and the consistency of fat replacing products, but an intensification of the cohesivity and a reduction of color, hardness and tackiness were detected in some samples. PMID- 22063292 TI - Influence of kappa-carrageenan on the thermal gelation of salt-soluble meat proteins. AB - Cooked ham-based model systems were prepared using salt-soluble meat protein isolate, kappa-carrageenan and sodium and potassium chloride. The pH was set to 6.2 using a 50mM PIPES-buffer. An experimental mixture design was used to study the effect of carrageenan on the structure build-up of the gelled meat products. In situ gelation experiments were carried out on a controlled-stress rheometer, while a texture analyzer was used to determine the large deformation behaviour. The water holding capacity was measured by a centrifugal technique and confocal scanning laser microscopy was used to visualize the microstructure of the gelled meat products. kappa-Carrageenan was found to increase the complex modulus, the gel strength and the water holding capacity, although these properties were mainly governed by the concentration of meat protein isolate. PMID- 22063293 TI - Characterisation of PSE zones in semimembranosus pig muscle. AB - Pig semimembranosus muscles, sampled from normal hams or from PSE-zones of defective hams, were analysed by histochemistry and electrophoretic techniques. PSE zones were characterised by a disorganisation of fibre alignment and a significant increase of inter fibre spacing (26.2% vs. 16.9%, p<0.05). Protein solubility was significantly lower in defective muscle (55.4 vs. 91.5mg/g, p<0.001). SDS-PAGE evidenced in such samples a lower abundance of the 97, 40 and 26kDa bands in the sarcoplasmic fraction and a higher abundance of the 97, 58, 34, 31, 15 and 11kDa bands in the myofibrillar fraction. Intensity of the MHC band (200kDa) was lower in PSE zone samples. By 2-D electrophoresis, it was shown that troponin T, MLC 1 and alpha-crystallin were less proteolysed in defective muscles, while creatine kinase fragments were more represented. One form of HSP 27 was absent from PSE zone samples. Overall, meat from PSE-zones and fast pH fall-PSE meat show numerous histological and biochemical similarities, particularly in their protein characteristics. PMID- 22063294 TI - Effects of diet and live weight at slaughter on kid meat quality. AB - Forty male twin kids of the Majorera breed were used in a 2*2 design, in which the diet, suckled on dam (SD) or milk replacer (MR) and live weight at slaughter (6 or 10kg) were the main variables. Muscle pH and colour (CIE, L*a*b*) were determined in the longissimus (LD), semimembranosus (SM) and triceps brachii (TB) muscles, immediately after slaughter and chilling (24h). Water-holding capacity, shear force, chemical composition (moisture, fat, protein and collagen content and solubility) were determined. Muscle fibre populations were also studied. SD kid meat was slightly more tender and juicy, and the Chroma value was lower than in MR animals. The meat from the kids that were slaughtered at 10kg was significantly darker in all muscles tested and slightly less tender 6kg LWS kid meat had more moisture and less protein than that of 10kg LWS kids. Muscle fibre area was statistically higher in the 10-kg LWS kids. It was concluded that the meat quality of the heavier kids was not significantly different from that of the lighter kids and that slaughter at the greater weight would result in more meat being marketed. PMID- 22063295 TI - Presence and characterisation of verotoxin producing E. coli in fresh Italian pork sausages, and preparation and use of an antibiotic-resistant strain for challenge studies. AB - One hundred and twenty six samples of fresh pork sausages were analysed for the presence of verocytotoxigenic Escherichia coli (VTEC). Selective enrichment followed by DNA extraction and PCR amplification of the stx1 and stx2 genes highlighted the occurrence of the above mentioned genes in 20 out of 126 samples screened. From the stx positive enriched cultures, isolation was performed on CT SMAC agar plates after immuno-magnetic separation of E. coli O157. Fifty three non-sorbitol fermenting isolates were obtained and further characterised, along with the reference strain E. coli ATCC 35150(T). All the isolates were characterised by PCR assays, assessing the presence of stx1, stx2, rfbE(O157:H7), eae and hlyA genes. The overall prevalence of VTEC was found to be 16%. VTEC strains were also characterised by plasmid profiling and REA-PFGE analysis, which allowed strain clustering into 5 and 8 groups, respectively. In addition, an antibiotic resistant E. coli O157:H7 strain was selected and used in challenge tests of raw pork at 4 degrees C. This strain could be selectively counted in the presence of a normal background microflora and it was shown that it could survive for 1week at 4 degrees C in the raw food studied. PMID- 22063296 TI - Use of ionizing radiation doses of 2 and 4kGy to control Listeria spp. and Escherichia coli O157:H7 on frozen meat trimmings used for dry fermented sausage production. AB - This study evaluated survival of Listeria spp. (four-strain mixture of Listeria innocua plus a non-virulent Listeria monocytogenes strain) and Escherichia coli O157:H7 strain ATCC 43888 during fermentation and ripening of Greek dry sausages formulated from meat and pork fat trimmings previously inoculated with ca. 6logcfug(-1) of the target bacteria and then irradiated in frozen (-25 degrees C) blocks at doses of 0 (control), 2 or 4kGy. Irradiation of the trimmings at 2kGy reduced initial contamination of the sausage batter with Listeria and E. coli O157:H7 by 1.3 and 2.0 logcfug(-1), respectively, while the corresponding reductions at 4kGy were 2.4 and 5.5 logcfug(-1), respectively. In fact, E. coli O157:H7 was eliminated by 4kGy at formulation (day 0) as compared to 7 and 21 days of ripening in samples treated at 2 and 0kGy, respectively. Despite the fact that irradiation assisted in faster declines of listeriae during fermentation, these bacteria showed a strong tailing during ripening, which was more pronounced in sausages irradiated at 4kGy. As a consequence, survival of Listeria in 28-day sausages irradiated at 2 or 4kGy was ca. 2 logcfug(-1) and similar (P>0.05) to that in non-irradiated samples. Irradiation showed promise for controlling E. coli O157:H7 and, to a lesser extent, L. monocytogenes in fermented sausages. PMID- 22063297 TI - Evaluation of peroxyacetic acid as a potential pre-grinding treatment for control of Escherichia coli O157:H7 and Salmonella Typhimurium on beef trimmings. AB - Peroxyacetic acid was evaluated in four separate trials for ability to reduce populations of Escherichia coli O157:H7 and Salmonella serotype Typhimurium on fresh beef trim. Trial 1 examined the effectiveness of peroxyacetic acid on individual pieces of fresh beef trim. Trial 2 evaluated the efficacy of peroxyacetic acid at low levels of contamination on batches of fresh beef trim. Trial 3 studied a washing effect of water. Lastly, Trial 4 compared the effectiveness of peroxyacetic acid to lactic acid. At various inoculation levels, peroxyacetic acid reduced populations of both pathogens by approximately 1.0log(10)CFU/cm(2) on fresh beef trim. Trial 3 showed that approximately half of the reductions found in Trials 1 and 2 were due to a washing effect of the water dip. In addition, as shown in Trial 1, increases in concentrations (>200ppm) did not significantly increase log(10) reductions of both pathogens. Following a water dip in Trial 4, peroxyacetic acid caused a reduction of 0.7log(10)CFU/cm(2) in E. coli O157:H7 and 1.0log(10)CFU/cm(2) in Salmonella Typhimurium, whereas lactic acid caused a reduction of 1.3log(10)CFU/cm(2) in E. coli O157:H7 and 2.1log(10)CFU/cm(2) in S. Typhimurium following the water dip. These results show that peroxyacetic acid was not more effective than 2% l-lactic acid in reducing pathogens on fresh beef trim. PMID- 22063298 TI - The pulmonary mesenchymal tissue layer is defective in an in vitro recombinant model of nitrofen-induced lung hypoplasia. AB - Despite modern treatments, congenital diaphragmatic hernia (CDH) remains associated with variable survival and significant morbidity. The associated pulmonary hypoplasia is a major determinant of outcome. To develop better treatments, improved comprehension of the pathogenesis of lung hypoplasia is warranted. We developed an in vitro cell recombinant model to mimic pulmonary hypoplasia and specifically to investigate epithelial-mesenchymal interactions and to decipher which tissue layer is primarily defective in nitrofen-induced CDH associated lung hypoplasia. Epithelial cells (E) and fibroblasts (F) were isolated from E19 control ((C)) and nitrofen-induced hypoplastic rat lungs ((N)). Cells were recombined and cultured as either homotypic [(F(C))(E(C)) and (F(N))(E(N))] or heterotypic [(F(C))(E(N)) and (F(N))(E(C))] recombinants. Recombinants containing F(N) fibroblasts had a thickened fibroblast tissue layer and there were fewer organized alveolar-like epithelial structures compared with those in control (F(C))(E(C)) recombinants. These F(N) recombinants exhibited a decrease in terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved caspase-3 positive cells. Cell proliferation was arrested in recombinants containing F(N) fibroblasts, which also exhibited increased p27(Kip1) and p57(Kip2) expression. In conclusion, fibroblasts, and not epithelial cells, appear to be the defective cell type in nitrofen-induced hypoplastic lungs due to a decreased ability to undergo apoptosis and maintain overall proliferation. This may explain the characteristic pulmonary interstitial thickening and hypoplasia observed in both nitrofen-induced hypoplastic lungs as well as human hypoplastic CDH lungs. PMID- 22063299 TI - Human memory Th17 cells express a functional histamine H4 receptor. AB - The histamine H4 receptor is functionally expressed on CD4(+) T cells and in particular on human CD4(+) Th2-polarized T cells. Interleukin (IL)-17-producing T cells (Th17 cells) represent a newly defined major CD4(+) T-cell subset, having been identified in psoriatic plaques and in acute skin lesions of atopic dermatitis where histamine is also present in high concentrations. To elucidate the role of the histamine H4 receptor (H4R) on these effector T cells, we polarized human memory T cells into Th17 cells. Further, we investigated H4R expression and assessed its function by real-time PCR, by a cytokine secretion assay of IL-17, and by electrophoretic mobility shift assay of activating protein 1 (AP-1). We show that Th17 cells polarized by IL-1beta together with IL-23 express the H4R on mRNA and protein level. Additionally, we identified IL-17 positive cells in psoriatic skin lesions. The IL-17-positive lymphocytes were all positive also for functional H4R. Stimulation with histamine or a H4R agonist increased the production of IL-17 and induced activating protein-1 in Th17 cells. In inflammatory skin diseases with enhanced histamine release, such as psoriasis and atopic dermatitis, histamine might foster the immunomodulatory potency of skin-infiltrating Th17 cells. PMID- 22063300 TI - Rise rate and timing variability of surface electromyographic activity during rhythmic drumming movements in the world's fastest drummer. AB - The winner of an international contest to find the world's fastest drummer (WFD) can perform repetitive wrist tapping movements with one hand using a handheld drumstick at 10Hz, much faster than the maximum tapping frequency of 5-7Hz in the general population. The muscle activity facilitating this improved performance, however, has only recently been explored. The present study investigated the rise rate and timing variability of surface electromyographic (EMG) activity of wrist flexor/extensor muscles in the WFD, and compared them with those in two control groups: non-drummers (NDs) and ordinary drummers (ODs). The WFD showed more rapid EMG amplitude rise, earlier decline of EMG activity, and more stable muscle activation time than the NDs and ODs. In addition, there was a significant correlation between the EMG rise rate and the duration of drum training in the group of drummers (i.e., ODs and WFD). These results indicate that the 10-Hz performance of the WFD was achieved by a 'sharper' and 'less noisy' burst pattern of wrist muscles, and that drum training would have the effect to increase the speed of development of muscle tension. PMID- 22063301 TI - Tablet preformulations of indomethacin-loaded mesoporous silicon microparticles. AB - In this study, indomethacin-loaded thermally oxidized mesoporous silicon microparticles (TOPSi-IMC) were formulated into tablets with excipients in order to improve the dissolution and permeability properties of the poorly soluble drug. Formulations of TOPSi-IMC particles and excipients were prepared at different TOPSi-IMC particle ratios (25, 30 and 35%). The formulations were compressed by direct compression technique with a single punch tablet machine. For comparison, a formulation containing the bulk IMC (indomethacin) and the same excipients without thermally oxidized mesoporous silicon microparticles particles (TOPSi) was prepared and compressed into tablets. The TOPSi-IMC tablets were characterised according to weight, thickness, crushing strength, disintegration time and dissolution rate. The results of this study show that TOPSi-IMC particles can be compressed to a conventional tablet. The release rate of the drug and its permeation across intestinal cells model (Caco-2) from TOPSi-IMC tablets was improved compared to the bulk IMC tablets. The dissolution rate and permeability of IMC from the tablets decreased with increasing ratio of the TOPSi IMC particles in the formulation. The phenomenon is, presumably, a result of the loss of unique pore structure of the particles due to deformation of the particles under the compression load. PMID- 22063302 TI - Obituary dr donald kinsman 20/5/1923-29/1/1998. PMID- 22063303 TI - An analysis of data relating to pig carcass quality and indices of stress collected in the European union. AB - Information from about 5500 pigs killed in five European countries was used to examine the relation of different measures of carcass and meat quality to one another and their relation to biochemical indices of stress in blood collected at slaughter. There were large differences in the prevalence of potentially PSE meat in pigs from the five countries and evidence of a wide range of stress encountered at slaughter. Relationships between the same measurements made in different muscles were generally good and consistent between countries. There were no apparent relationships between indices of stress and characteristics associated with PSE meat. In contrast, greater stress tended to be reflected in more DFD meat. Based on the association between the level of skin blemish and increased muscle ultimate pH values a probable factor contributing to this was fighting between mixed groups of unfamiliar animals. PMID- 22063304 TI - Effects of salt and temperature on proteolysis during ripening of Iberian ham. AB - Fifty-five hams from Iberian pigs were processed using two different dry-curing techniques, traditional and modern. Salt content, non-protein nitrogen and its fractions (peptide, amino acid and volatile basic nitrogen) from Biceps femoris muscles were quantified. The existence of an overlapping effect of both temperature and salt content on the general non-protein nitrogen production was observed. The most intense proteolytic breakdown took place when higher temperatures were reached during the drying stage. The difference in salt concentration seems to contribute to generating different quantities in the non protein nitrogen fractions. The inclusion at the end of the cellar stage of a stuffing period would permit increasing the accumulation of free amino acid in high salted hams. PMID- 22063305 TI - Prediction of the feeding background of Iberian pigs using the fatty acid profile of subcutaneous, muscle and hepatic fat. AB - Thirty Iberian pigs weighing 95 kg were randomly distributed into three groups of 10 animals each and fattened in three traditional management systems ['montanera' (MO), fed extensively on acorns, 'cebo' (CE) fed on a commercial diet and 'recebo' (RE), fed on acorns and a commercial diet]. Fatty acids from the Masseter muscle, lard and liver were analysed. In the lard, fatty acid profiles from MO and RE pigs presented minor differences; however, in the liver, RE pigs showed differences to MO pigs in most of the fatty acids studied. This suggests that the muscle and especially the liver fatty acid profile reflects the feeding regime during the last phase of feeding, while the lard reflects longer term differences. PMID- 22063306 TI - Effect of dietary vitamin E supplementation for one week before slaughter on drip, colour and lipid stability during display in Japanese Black steer beef. AB - Effects of dietary vitamin E supplementation for one week on drip, colour and lipid stability in raw beef steaks were studied. Four Japanese Black steers were fed no supplemental vitamin E and four were supplemented with 5000 mg of dl-alpha tocopherol per animal daily for one week before slaughter. Steak samples from psoas major and longissimus thoracis muscles were over-wrapped with PVC film and displayed under fluorescent lights at 4 degrees C for 10 days. Drip loss percentages, L(*), a(*) and b(*) values, metmyoglobin percentages, and 2 thiobarbituric acid reactive substances values were determined at day 1, 4, 7 and 10. Dietary vitamin E supplementation increased (p < 0.01) alpha-tocopherol concentration in the plasma, liver and muscles. Vitamin E supplementation reduced (p < 0.001) drip loss compared to the control. Vitamin E supplementation maintained (p < 0.001) redness and retarded (p < 0.01) metmyoglobin formation in beef steak from day 4 to day 10 of display compared to the control. Vitamin E supplementation delayed (p < 0.001) lipid oxidation during 10 days of display compared to the control. The data indicated that dietary vitamin E supplementation for one week prior to slaughter improved lipid stability better than drip and colour stability in beef steak during 10 days of display. PMID- 22063307 TI - The effect of cooking on the chemical composition of meat products with special reference to fat loss. AB - The chemical composition and energy content of four product categories (sausages, restructured steaks, burgers and minced beef) were determined before and after cooking. Two cooking methods were used for each product category: sausages and burgers were fried or grilled, restructured steaks were grilled or cooked in an oven whilst mince was either boiled or lightly fried and then boiled to simulate domestic practice. Based on an initial 100 g of product and excluding the low fat products included in the survey, the average weights after cooking were 78, 73, 72 and 70 g for the sausages, restructured steaks, burgers and minced beef, respectively; average fat contents before and after cooking were 22 and 17 g for the sausages, 17 and 14 g for the restructured steaks, 25 and 16 g for the beef burgers, and 19 and 7 g for the mince; and average energy contents before and after cooking were 1215 and 1016 kJ for the sausages, 958 and 815 kJ for the restructured steaks, 1244 and 906 kJ for the burgers and 1009 and 544 kJ for the mince. For a given product type, cooking method was relatively unimportant; the cooking loss, fat loss and energy content of the cooked product being more dependent on product formulation and manufacturing process. The survey included a low fat sausage, a low fat burger, a lean mince and an extra lean mince with fat contents of 8.7, 7.5, 12.4 and 5.2%, respectively. Overall weight losses during cooking were similar to standard products, though low fat products lost proportionally more water and less fat. Frying resulted in a slight gain in fat content for the low fat sausages and burgers, based on an initial 100 g of product, though fried low fat products still had lower fat and energy contents than standard products. It is argued that national consumption figures should take into account the losses that occur during cooking to avoid overestimating fat and energy intake levels. PMID- 22063308 TI - Effects of grilling to 80 degrees C on the chemical composition of pork loin chops and some observations on the UK National Food Survey estimate of fat consumption. AB - The physical and chemical composition of pork loin chops was investigated, examining the changes that occurred in (i) the whole chop, (ii) the fat tissue and (iii) the lean tissue by grilling to 80 degrees C. Adjacent 25 mm thick chops, with backfat and rind attached, were cut from loins of 90 kg live weight pigs having a fat thickness (P(2)) of 11 mm, representative of current UK production. One chop was analysed fresh by dissection and standard analytical techniques and the other after grilling. Weights of chop (including rind) before and after cooking were 210 and 136 g, respectively. The average weight loss for the whole chop was 35%; the weight loss from fat, 44%, being greater than that from lean, 34%, or rind, 27%, the latter accounting for 14% of the whole raw chop. When expressed conventionally, on a percentage basis, the fat content of the whole rindless chop increased from 22 to 23%, and the fat content of the lean increased from 5.5 to 9%. In absolute terms, based on an initial 100 g, the fat content in the whole chop reduced from 22 to 15 g, with a slight increase in the fat content of the lean, from 5.5 to 6.0 g. It is argued that the National Food Survey (NFS) approach of estimating fat consumption on the basis of the fat content of the raw product is flawed. The terms 'meat consumption' and 'fat consumption' are misleading since they reflect amounts purchased rather than the amount of meat and fat actually consumed, making no allowance for fat lost during cooking or for subcutaneous fat removed by consumers before consumption. Actual fat consumption from cooked meat and meat products, after allowing for a 25% fat loss during cooking and trimming of visible fat, is estimated at 10.3 g per person per day compared with the NFS estimate of 18.1 g. PMID- 22063309 TI - Effect of dietary vitamin E supplementation on pork quality. AB - The purpose of this experiment was to examine the effect of dietary vitamin E supplementation on pork quality, and in particular on colour stability. Crossbred pigs (n = 72) at a mean weight of 44 kg were assigned to one of two treatments. One group received, during a period of 84 days prior to slaughter, a tapioca based diet, which contained 8 mg vitamin E per kg feed. The other group received during this period the same diet, except it was supplemented with 200 mg vitamin E per kg feed. Muscle samples of longissimus thoracis and lumborum (LL) and psoas (PM) were collected at 24 hr post mortem and meat quality was assessed: pH, drip and cooking loss, shear force and intramuscular fat content. Colour stability was evaluated in fresh muscle (LL and PM) and after freezing (LL only) by measuring redness (a(*)-values) during 6 days of storage at 7 degrees C. TBA-values and microbiological counts were also determined during storage. Results showed that extra dietary vitamin E had no effect on pig performance (daily gain, feed efficiency, lean meat percentage) nor on meat quality traits. The vitamin E levels were five times higher in the muscles of the treated group than the control group. In comparison with fresh LL muscle, colour stability was lower in PM and after freezing. In both muscles, the vitamin E treatment reduced TBA values, in particular after frozen storage. No effect was found on microbiological counts. Colour stability was improved in LL after 6 days of storage, but not in PM. The effect in LL is too late to be of practical significance, since pork is usually sold well before that time in The Netherlands. It is suggested that variation in feedstuff composition of the diet may possibly explain part of the variable results reported in literature for the effect of vitamin E supplementation on colour stability of pork. PMID- 22063310 TI - Dry fermented sausages manufactured with different amounts of commercial proteinases: Evolution of total free alpha-NH(2)-N groups and sensory evaluation of the texture. AB - Different doses of some commercial proteinases (Neutrase, Alcalase, HT Proteolytic and Fungal Protease) were tested in the manufacture of two types of dry fermented sausages in order to choose the highest concentration that having proteolytic effect did not show texture problems. The different units in which their activity was expressed was one of the difficulties found in this work. All of them showed proteolytic activity in these products but with different intensity, leading in some cases to an excessive softening of the sausages. The effect of Fungal Protease became apparent earlier in a 16 mm particle size sausage than in a 3 mm particle size sausage. Careful dose selection for every proteinase could make it possible to ensure a proteolytic effect that could accelerate the maturation without texture defects. PMID- 22063311 TI - Liberation of peptides during meat storage and their interaction with proteinase activity. AB - The content of nitrogenous material extracted in perchloric acid from kid longissimus lumborum (LL), semimembranosus (Sm) and triceps brachii (TB) muscles increased 30% during storage for three weeks at 4 degrees C. The extract of fresh muscle contained a range of molecular sizes up to 13 kDa, the majority less than 4 kDa. The amount of the larger polypeptides (> 4 kDa) extracted from meat decreased to 50% of its initial level in meat stored for five days and to 20% after 25 days. The amount of intermediate sized peptides (1.9 to 4 kDa) remained largely constant throughout storage of meat of normal pH, whilst in meat of high ultimate pH, they showed a transitory increase during the first two weeks storage. Smaller size peptides increased with storage time; increasing more slowly in meat of high ultimate pH. This time-dependent pH effect indicates a sequential autolysis involving neutral followed by acidic proteolytic and peptidic activity. Calpain from beef muscle degraded peptides in the extract and the extract acted as a competitor against a synthetic substrate. This implies that the in-situ autolysis and tenderisation of meat postmortem could be reduced by peptide products. PMID- 22063312 TI - Effect of rigor temperature and frozen storage on functional properties of hot boned manufacturing beef. AB - Within 45 min post-mortem, 10mm thick strips of semitendinosus muscle from both unstimulated and high voltage stimulated heifer sides were held at 0, 5, 10, 25 and 35 degrees C for 24 hr, during which they entered rigor. Half the samples were frozen and stored at -20 degrees C for one month. The pH, sarcomere length, drip, total (TPS), myofibrillar (MPS) and sarcoplasmic (SPS) protein solubilities, and Hunter L (*), a (*) and b (*) values were determined at 24 hr and on thawed samples. Electrical stimulation did not significantly affect any of the parameters measured. The ultimate pH of samples entering rigor at 10 and 25 degrees C was lower (p < 0.001) than that of samples held at the other temperatures. Rather surprisingly, there was no significant difference in sarcomere length due to rigor temperature. Samples entering rigor at 35 degrees C had lower TPS, MPS and SPS values than samples held at 0 to 25 degrees C (p < 0.001). The MPS increased with rigor temperature up to 25 degrees C (p < 0.001). Drip and total moisture losses, and Hunter L (*), a (*) and b (*) values also increased with rigor temperature (p < 0.001) whereas SPS decreased and NMR meat water spin-lattice relaxation time (T1) shortened with increasing rigor temperature (p < 0.001). Hue angle and cook loss decreased with rigor temperature in 24 hr samples but increased with rigor temperature in frozen samples. After frozen storage, SPS, T1, cook loss and Hunter L (*), a (*), b (*) values decreased, but TPS, MPS, drip losses and hue angle increased. There were significant (p < 0.05) correlations between SPS, hue angle, drip losses and T1. PMID- 22063314 TI - Corrigendum. PMID- 22063313 TI - Correlations between successive measurements of myofibrillar resistance of raw Longissimus dorsi muscle during ageing. AB - The feasibility of meat classification soon after rigor, based on an ageing criterion, was investigated with a view to obtain sets of regularly aged meat as well as to optimize storage. Muscle fibre resistance was measured on the m. longissimus dorsi of 45 heifers on days 1, 2, 8 and 14, and the resistance values obtained on different days were correlated. Resistance on day 2 was predictive of about 65% of the variation observed on day 8, i.e. when the meat has reached approximately 92% of the tenderization recorded between days 1 and 14. In this study, the predictions based on day 1 resistance were less accurate because the baseline reference was too close to rigor. A class defined at day 2 as the meat which has a resistance lower than 20 N cm(-2), will give fully aged meat at day 8. This class represent 52% of the initial population The various classes of meat, which reach full ageing at different times, can be despatched through variable length marketing circuits so as to achieve full ageing before getting to the consumers. PMID- 22063315 TI - A label-free immunosensor by controlled fabrication of monoclonal antibodies and gold nanoparticles inside the mesopores. AB - A label-free immunosensor for the detection of alpha-fetoprotein (AFP) is proposed based on controlled fabrication of monoclonal antibodies of AFP (anti AFP) and gold nanoparticles (GNPs) inside the pores of mesoporous silica (MPS). The silanol groups on the internal pore walls were grafted by aminopropyltriethoxyl silane, whereas the silanol groups on the external surface of MPS were blocked by trimethylchlorosilane (TMCS). Thus, anti-AFP and GNPs could be confined inside the mesopores of TMCS-MPS by the covalent linking with the amino groups. The prepared anti-AFP/GNPs/TMCS-MPS particles were used to modify glassy carbon electrode (GCE) to construct a label-free immunosensor. After incubating the sample AFP with the anti-AFP/GNPs/TMCS-MPS/GCE, the immunoconjugates were formed on the surface of GCE and the spatial block increased. Thus, the peak current decreased with increasing concentrations of AFP. GNPs inside the mesopores could promote the electron transportation through the pore channel. Under the optimal experimental conditions, the fabricated immunosensor could detect AFP in a linear range from 1.0 to 90 ng ml(-1) with a detection limit of 0.2 ng ml(-1) (3sigma). It provided a novel alternative method for the label-free determination of other antigens. PMID- 22063317 TI - Analytical methods for authentication of fresh vs. thawed meat - A review. AB - Proper labeling of meat products is important to ensure fair-trading and to enable consumers to make informed choices. Different investigations indicate that wrong labeling where thawed meat is labeled as fresh meat is present in 8-15% of analyzed samples. Enforcement of regulations requires adequate analytical methods where enzymatic-, DNA based-, spectroscopic-, bio imaging- and sensory techniques constitute the majority of published papers. The molecular changes that these techniques detect are described. The capability of both discrimination between fresh and thawed meat, and determination of frozen storage time are discussed for each of the analytical techniques. The products included in this review are primarily whole meat from Bos taurus (cow), Sus scrofus (pig) and Gallus gallus (chicken). The best analytical choice in the discrimination of fresh vs. thawed meat is concluded to be a combination of analytical methods. PMID- 22063316 TI - Antigen-specific prevention of type 1 diabetes in NOD mice is ameliorated by OX40 agonist treatment. AB - Antigen-specific therapies are possibly the safest approach to prevent type 1 diabetes (T1D). However their clinical translation has yielded poor results and greater efforts need to be put into the development of novel strategies to ameliorate their clinical outcome. OX40 is a costimulatory molecule expressed by T cells after antigen recognition and has been implicated in the control effector but also regulatory T cells (Tregs) function in vivo. The activity of OX40 signal on Tregs function has been controversial. In this context we investigated whether an anti-OX40 agonist antibody treatment can ameliorate antigen-specific immune intervention for the prevention of T1D. We show that treatment of non-obese diabetic (NOD) mice with an OX40 agonistic antibody (OX86) reduced type 1 diabetes (T1D) incidence by inducing both CD4(+)CD25(+)Foxp3(+) Tregs and CD4(+)Foxp3(-) T cells expressing the latency-associated peptide (LAP). These OX86-induced CD4(+)Foxp3(-)LAP(+) T cells also demonstrated suppressive activity in vitro. A significant increase in protection was observed when OX86 was combined with insulin B9:23 (insB9:23) peptide immunizations. Synergy resulted from an expansion of IL-10-expressing insB9:23-reactive Tregs which augmented the proportion of CD4(+) T cells with in vivo suppressive activity. Consequently, CD4(+) T cells purified from OX86/insB9:23 combination treatment prevented T1D development when adoptively transferred into recipient mice. These findings suggest that the requirement for OX40 signaling by antigen-induced Tregs can be dominant over its well-documented need for effector memory cell function and may have potentially important implications for improving the clinical translation of antigen-specific prevention of T1D and possibly other autoimmune disorders. PMID- 22063318 TI - The antimicrobial effect of thyme essential oil, nisin and their combination against Escherichia coli O157:H7 in minced beef during refrigerated storage. AB - The antimicrobial effect of thyme essential oil (EO) at supplementation levels of 0.3%, 0.6% or 0.9%, nisin at 500 or 1000IU/g, and their combination, on Escherichia coli O157:H7 was examined in both tryptic soy broth (TSB) and minced beef meat. EO at 0.3% possessed a weak antibacterial activity against the pathogen in TSB, whereas at 0.9% showed unacceptable organoleptic properties in minced meat. Thus, only the level of 0.6% of EO was further examined against the pathogens in minced meat. Treatment of minced beef meat with EO at 0.6% showed an inhibitory activity against E. coli O157:H7 during storage at 10 degrees C, but not at 4 degrees C. Treatment of minced beef meat or TSB with nisin at 500 or 1000IU/g did not show any antibacterial activity against E. coli O157:H7. The combination of EO at 0.6% and nisin at 500 or 1000IU/g showed an additive effect against the pathogen, which was higher during storage at 10 degrees C than at 4 degrees C. PMID- 22063319 TI - Dry fermented sausages enriched with lycopene from tomato peel. AB - Tomato industries yield a high amount of by-products mainly tomato peel and seeds. Since tomato peel is rich in lycopene, the direct addition of peel to food products could be a way to use this by-product to obtain a new products enriched in lycopene. This work describes experiments performed to develop dry fermented sausages (salchichon) containing this carotene. 0%, 0.6%, 0.9% and 1.2% (w/w) of dry tomato peel was added to the meat mixture used in sausage manufacture. A slight losts of lycopene was detected after 21 days ripening, however, levels remained between 0.26 and 0.58mg of lycopene/100g of sausage. The sensory and textural properties and overall acceptability of all sausages were good, indicating that tomato peel could be added to dry fermented sausages to produce a meat product enriched in lycopene. PMID- 22063320 TI - Effects of addition of carrot dietary fibre on the ripening process of a dry fermented sausage (sobrassada). AB - Four formulations of a dry fermented sausage, known as sobrassada, containing different percentages of carrot dietary fibre (DF) [3% (S3), 6% (S6), 9% (S9) and 12% (S12) (w/w)] were analyzed for various physico-chemical and microbiological parameters and sensory attributes. The ripening process was monitored throughout storage. The pH of DF-supplemented sobrassadas was critically affected during ripening by the amount of DF incorporated, the values for sobrassada samples containing over 3% of DF suggested that the fermentation process in these samples was not successful. In addition, textural parameters, such as hardness and compression work, were significantly affected by the addition of over 3% of DF. The lipolytic process, one of the major biochemical events, was only affected when relatively large percentages of DF concentrate were incorporated. Thus, S3 and S6 samples exhibited similar free fatty acid profiles to the control throughout ripening. PMID- 22063321 TI - Effect of pre-emulsified fish oil - as source of PUFA n-3 - on microstructure and sensory properties of mortadella, a Spanish bologna-type sausage. AB - Conventional and low-fat cooked sausages (cursive) were prepared with fish oil as a source of n-3 polyunsaturated fatty acids. Fish oil was incorporated pre emulsified with caseinates and water. Pre-emulsion was added in sufficient amounts to give fish oil levels of 1-6% in the final product. Lipid oxidation was determined (TBARs index) and instrumental measures of colour and texture were carried out. A sensory analysis was performed in which sensory parameters were evaluated by a hedonic test. There were no significant changes in TBAR values of final products being similar in both control and fish oil added sausages. In general terms, a slight increase in hardness and work of shearing were observed at the higher fish oil levels independently of the fat content. Sausages were analysed after 90 days of storage under refrigeration and similar results were observed. Microstructure of sausages was also studied by scanning electron microscopy (SEM) and a more compact structure was observed when the high levels were assayed. However, all sausages were well accepted when sensory quality was evaluated. Fat composition showed an increase in n-3 PUFA yielding a n-6/n-3 ratio close to 2, which is considered as healthier. For this, the incorporation of fish oil pre-emulsified seems to be a good option to include n-3 PUFA in cooked meat products, obtaining sensorially adequate and healthier stable sausages. PMID- 22063322 TI - Purification and characterization of a bacteriocin produced by Leuconostoc mesenteroides E131. AB - Leuconostoc mesenteroides E131, isolated from Greek traditional fermented sausage, prepared without the addition of starters, produces a bacteriocin which is active against the pathogen Listeria monocytogenes. The bacteriocin was purified by 50% ammonium sulphate precipitation, cation exchange, and reverse phase chromatography. Bacteriocin is active at pH values between 4.0 and 9.0 and retains activity after incubation for 1h at 100 degrees C. Proteolytic enzymes inactivated the bacteriocin after 1h of incubation, while renin resulted in full inactivation only after 24h. Lipase resulted in full inactivation after 4h. Applying molecular methods, it was determined that the bacteriocin produced, named as mesenterocin E131, was identical to mesenterocin Y105 and was expressed during the exponential growth phase. PMID- 22063323 TI - Determination of volatile compounds in San Daniele ham using headspace GC-MS. AB - The volatile fraction of San Daniele hams was evaluated in barrows and gilts belonging to two commercial breeds. A group of 120 pigs, reared under the same conditions, were slaughtered, and the right ham seasoned/cured for 12 months, in accordance with the San Daniele Consortium protocol. At the end of ripening, 16 hams (four of each gender and breed) were selected and analysed for volatile composition, using a dynamic headspace gas chromatography-mass spectrometry (DHS GC-MS) technique. Seventy five compounds belonging to eight different chemical groups were identified in the hams. Alcohols were the most abundant constituents (41.38%) followed by aldehydes (31.53%). The possibility of classifying hams according breed and gender, using volatile compounds as independent variables, was analysed by principal component analysis, alcohols were the most suitable compounds to discriminate hams. Data from a larger number of samples are required to validate the conclusions. PMID- 22063324 TI - The influence of seasonal temperatures on meat quality characteristics of hot boned, m. psoas major and minor, from goats and sheep. AB - Samples of psoas major and minor muscles were randomly collected weekly from 203 (99 hot and 104 cool seasons) Omani goats, 215 (106 hot and 109 cool seasons) Omani sheep, 212 (104 hot and 108 cool seasons) Somali goats, 242 (127 hot and 115 cool seasons) Somali sheep and 211 (110 hot and 101 cool seasons) Australian Merino sheep slaughtered at the Central Slaughterhouse in Oman to investigate the effect of season on meat quality. The collection period was during November 2004 October 2005 and divided into two seasons according to ambient temperatures and relative humidity. These were termed: cool season (average temperature of 21 degrees C and 59% relative humidity and hot season (average temperature of 35 degrees C and 47% relative humidity). Muscles collected during the hot season had significantly (P<0.05) higher ultimate pH values (5.78) than those collected during the cool season (5.65). Myofibrillar fragmentation index was significantly (P<0.05) higher for hot season samples (86.88%) than for cool season samples (85.59%). Expressed juice was significantly (P<0.05) higher for cool season samples (36.84) than for hot season samples (35.74). Goat meat from the hot seasonal group was significantly (P<0.05) darker than the cold season group based on L* (37.6 vs. 39.6), a* (20.0 vs. 23.3) and b* (3.6 vs. 4.2) colour measurements. These results indicated that high ambient temperatures had caused an increase in muscle ultimate pH leading to significant effects on meat quality. PMID- 22063325 TI - Authentication of meat from game and domestic species by SNaPshot minisequencing analysis. AB - The aim of the present study is to develop an assay for the specific identification of meat from Capreolus capreolus, Cervus elaphus, Capra ibex, Rupicapra rupicapra, targeting sequences of the cytochrome b (cyt b) gene of mitochondrial DNA. The assay is also intended to enable differentiation between meat from these wild species as well as Ovis aries, Capra hircus, Bubalus bubalis, Bos taurus and Sus scrofa domestic species. The primers used in the preliminary PCR were designed in well conserved regions upstream and downstream of the diagnosis sites. They successfully amplified a conserved 232bp region from the cyt b gene of all the species taken into consideration. The sites of diagnosis have been interrogated using a minisequencing reaction and capillary electrophoresis. All the results of the multiplex PER (primer extension reaction) test were confirmed by fragment sequencing. The assay offers the possibility of discriminating nine species at the same time. PMID- 22063326 TI - Carcass and meat quality of Assaf milk fed lambs: Effect of rearing system and sex. AB - The effect of sex and rearing system on growth and carcass and meat characteristics of milk fed Assaf lambs was studied. Thirty-six lambs, 18 males and 18 females were used. Twelve lambs remained with their mothers throughout the experiment (NR). Within 24-36h of birth, the rest were housed individually and fed twice a day ad libitum (AAR) or at 70% of ad libitum consumption (RAR) with reconstituted cow's milk. Sex did not affect animal performance, yet females showed higher carcass and non-carcass fat deposits. NR lambs showed greater BWG than AAR fed lambs, and AAR, higher than the RAR. Differences between naturally and artificially reared lambs in CCW and killing out percentage were not significant. Empty digestive tract and mesenteric fat weights were greater for RAR than NR lambs, with the AAR lambs demonstrating intermediate values; conversely, omental fat was greater in NR lambs. Carcass ether extract content was greater for NR lambs, possibly due to the greater growth. Use of ad libitum cow's milk substitute in suckling lambs twice a day resulted in less body weight gain but similar killing out percentages compared to naturally raised lambs. A 70% restricted supply increased the days in suckling and reduced carcass fatness and compactness. Except for water loss, which was less in NR than artificially fed lambs, no differences were found in meat characteristics. PMID- 22063327 TI - Texture changes in dry-cured ham pieces by mild thermal treatments at the end of the drying process. AB - The present study evaluated the effects of mild thermal treatments at the end of the drying process on physicochemical characteristics and instrumental and sensory texture in dry-cured ham. Experiment 1: effect of thermal treatments (4 46 degrees C) for 4h and 24h. Experiment 2: time effect (4-168h) of thermal treatments at 30 degrees C and 36 degrees C. Both experiments were done on small dry-cured ham dices. Experiment 3: time effect (4-168h) of thermal treatment at 30 degrees C on both instrumental and sensory texture of 4-cm-thick sections of dry-cured ham. The thermal treatment at 30 degrees C for 168h on both dry-cured ham muscle dices (20mm*20mm*15mm) and dry-cured ham sections (4cmthick) decreased softness, adhesiveness and pastiness in BF muscle, without increasing hardness in SM muscle or affecting moisture, a(w) and proteolysis index. PMID- 22063328 TI - Meat and fat colour as a tool to trace grass-feeding systems in light lamb production. AB - Ninety-five lambs were fed as follows: lambs and dams grazing alfalfa (Gr); As Gr but lambs had access to concentrate (Gr+S); ewes grazed and lambs received milk and concentrate until weaning and thereafter concentrate and straw (Rat-Gr); ewes and lambs were stall-fed (Ind). Lambs were slaughtered at 22-24 kg of live-weight and fat and M. rectus abdominis colour measured. Visual appraisal scores of Gr and Ind were significantly different. The absolute value of the integral of the translated spectrum (SUM) was greater in Gr and GR+S. A discriminate analysis was able to discriminate between grass-fed and indoor-fed lambs. A logistic regression including SUM and b(*) classify correctly 99.1% of carcasses. A equation is proposed to calculate the probability of one carcass to do not belongs to Gr or Gr+S group (PNA): [Formula: see text] . PMID- 22063329 TI - Flavour formation in pork semimembranosus: Combination of pan-temperature and raw meat quality. AB - Flavour development and overall eating quality of pork semimembranosus were investigated with regard to different raw meat qualities (feeding/fasting strategy; control/low glycogen level, gender; castrate/female, slaughter live weight; 84kg/110kg) combined with frying temperature (150 degrees C/240 degrees C). It was further investigated whether the precursor levels of glycogen, IMP, inosine, and hypoxanthine in the raw meat were correlated to the raw meat quality and fried/grilled attributes. Pork schnitzels were fried on a pan (155 degrees C) or grill-pan (240-250 degrees C) to a core temperature of 70 degrees C. Frying temperature was the one factor with greatest influence on the sensory attributes, and pan-grilled schnitzels had significantly higher scores in fried/grilled attributes regardless of meat quality compared to pan-fried schnitzels. Texture was not appreciably influenced by any treatment. There was no correlation between precursor levels and raw meat qualities or fried sensory attributes. Gender and slaughter live-weight had no pronounced influence on flavour and overall eating quality. PMID- 22063330 TI - Identifying muscle and processing combinations suitable for use as beef for fajitas. AB - Four different treatments-control, papain, blade tenderization, and papain+blade tenderization-were applied to sixty USDA Choice M. diaphragma pars costalis, M. transversus abdominis, M. obliquus abdominis internus, M. rhomboideus, M. trapezius, M. latissimus, and M. serratus ventralis. Trained (n=6) and consumer (n=81) panelists scored papain samples higher for most sensory traits. Treatment tended not to affect the palatability scores of the M. diaphragma pars costalis and M. serratus ventralis, which tended to receive higher scores in comparison to the other muscles. Consumers were willing to purchase the M. latissimus and M. serratus ventralis treated with papain+blade tenderization and papain, respectively, and these muscles performed well enough to be considered as alternatives in the beef fajita market. PMID- 22063331 TI - Biogenic amine production by Gram-positive bacteria isolated from Spanish dry cured "chorizo" sausage treated with high pressure and kept in chilled storage. AB - We studied the production of biogenic amines by 200 strains of lactic acid bacteria and staphylococci isolated during chilled storage from samples of Spanish dry-cured "chorizo" sausage treated with high-pressure. The presence of biogenic amines in a decarboxylase synthetic broth was confirmed by ion-exchange chromatography. beta-phenylethylamine was the biogenic amine more frequently produced (22.5%), followed by tyramine (7.5%). In tyramine producer-strains the presence of a tyrosine decarboxylase gene was confirmed by PCR. Among lactic acid bacteria, the production of tyramine was mainly related to the species Lactobacillus curvatus. Most of the L. curvatus strains were also beta phenylethylamine-producers. In relation to staphylococci, tyramine-production was mainly associated to Staphylococcus carnosus strains. The S. carnosus strains analysed in this study produced beta-phenylethylamine or beta-phenylethylamine and tyramine simultaneously. RAPD-PCR results indicated that the biogenic amine producer S. carnosus population changes along storage independently of the high pressure treatment. PMID- 22063332 TI - Effects of pork/beef levels and various casings on quality properties of semi dried jerky. AB - The aim of this study was to investigate the effects of pork/beef levels and the casings on the quality properties of semi-dried jerky. The pork/beef levels in the four test formulations were as follows: T-1 (pork: beef=100:0), T-2 (95:5), T 3 (90:10), and T-4 (80:20). After tumbling for 30min with curing solution, the cured meats were stuffed into natural sheep casings, collagen casings, or cellulose casings, and then dried. The restructured jerky with cellulose casing had the lowest water content and the highest protein content, with no significant differences between various formulations. There were no significant differences among all formulations with regard to pH and total microbial counts, and jerky with cellulose casing had the lowest value of water activity. The processing yields of jerky made from the T-3 formulation were not significantly different with the various casings. The shear force of jerky with cellulose casing was lower than with other casings, and the metmyoglobin contents were more than 85% in all formulations. With regard to sensory properties, jerky made with the T-3 formulation and cellulose casings rated most favorable in evaluations than other treatments. PMID- 22063333 TI - Microbial, physical-chemical and sensory spoilage during the refrigerated storage of cooked pork loin processed by the sous vide method. AB - The aim was to study spoilage during the refrigerated storage of cooked pork loin processed by the sous vide method. Samples were packaged under vacuum into polyamide-polypropylene pouches, cooked at an oven temperature/time of 70 degrees C/12h, chilled at 3 degrees C and stored at 2 degrees C for 0, 5 or 10 weeks. Microbial (psychrotrophs, lactic acid bacteria, Enterobacteriaceae, moulds and yeasts), physical-chemical (pH, water activity, TBARS, acidity, L(*)a(*)b(*) colour, texture profile analysis and shear force) and sensory (appearance, odour, flavour, texture and acceptance) parameters were determined. The results showed that sensory spoilage preceded microbiological spoilage of sous vide pork loin. Counts bellow 1logcfu/g of psychrotrophs, anaerobic psychrotrophs, Enterobacteriaceae and lactic acid bacteria were detected in any control week, while moderate counts (2-3logcfu/g) of moulds and yeasts were found. Minor changes in water activity, lipid oxidation, CIELab colour, hardness, cohesiveness or gumminess were associated with spoilage of pork loin, only decreases of lactic acid, springiness and shear force were observed. The pork loin was unacceptable after 10 weeks. This loss of acceptance was mainly due to the deterioration of meaty flavour and odour, although the loss of appearance, juiciness and firmness also contributed. Moderate warmed-over and rancidity were detected. The sensory analysis was the most effective method for determining the shelf life of the sous vide pork-based dishes. PMID- 22063334 TI - Effect of the insulin-like growth factor-II and RYR1 genotype in pigs on carcass and meat quality traits. AB - Recently, a new QTN (quantitative trait nucleotide), which is located in the regulatory sequence of the imprinted IGF-II gene was discovered in the pig and is associated with a significant increase in IGF-II mRNA expression in skeletal muscle during postnatal growth. The aim of the current study was to investigate the effect of the IGF-II paternal allele (Apat and Gpat animals that inherited, respectively, the mutant and wild type paternal allele of interest) on carcass and meat quality traits in Nn and NN RYR1 genotypes. A total of 141 animals were measured, almost equally distributed over the IGF-II and RYR1 genotypes and gender. The Apat allele increased carcass lean meat percentage with approximately 4.5% (P<0.001) as a result of decreased backfat thickness. Average live weight daily gain was not affected, hence average daily lean meat gain was significantly higher for Apat compared to Gpat animals. The IGF-II mutation had no noticeable effect on meat quality in contrast with the RYR1 mutation. No interaction effects of both mutations on meat quality were noticed. PMID- 22063335 TI - Eating quality of pork from pure breeds and DLY studied by focus group research and meat quality analyses. AB - The eating quality of pan-fried pork chops from the pure breeds of Duroc, Hampshire, Black spotted and Wild pigs, and of the cross-breed of Duroc, Landrace and Yorkshire (DLY) was investigated by focus group research in combination with analyses of raw meat quality. The three focus groups, all consisting of young consumers, generally agreed in their description of the eating quality of the five breeds. The focus group methodology was found to be an informative method for the sensory evaluation of pork chops. Chemical and physical analyses of raw meat quality were performed in parallel with the focus group research, and this combination proved useful. The chemical and physical analyses generally supported the focus group evaluation, and differences between the breeds could be explained. Duroc was the breed with the overall best eating quality, while Hampshire had the lowest overall eating quality. DLY, Black spotted, and Wild pigs were intermediate, though not similar. PMID- 22063336 TI - Relationship between sensory attributes and volatile compounds qualifying dry cured hams. AB - This work studies the relationship between 45 volatile compounds and 17 sensory attributes (13 flavour perceptions) of dry-cured hams. Volatile compounds were quantified by SPME-GC while the sensory assessment was carried out by 13 panellists. GC-sniffing was used to determine the odour impact zones of the chromatogram. The odour thresholds of the volatile compounds and their sensory characterisation were determined by dilution analysis. Six sensory attributes (acorn odour and flavour, rancid odour, rancid taste, fat rancid and fat pungent flavours) were explained by regression equations (adjusted -R(2)?0.70) based on ten compounds: benzaldehyde, 2-heptanone, hexanal, hexanol, limonene, 3 methylbutanal, 3-methylbutanol, 2-nonanone, octanol, pentanol. Acorn flavour attribute was successfully emulated by mixing the volatile compounds selected by the equation. Its odour was evaluated by assessors that gave a sensory description that matches with the target. All the procedures performed for the elucidation of volatile-attribute relations showed a basic agreement in their results. PMID- 22063337 TI - Productive performance and meat quality of Mouflon*Sarda and Sarda*Sarda suckling lambs. AB - The objective of this study was to compare slaughtering performance, carcass characteristics, and meat quality in lambs of two different genotypes. Sixteen crossbred Mouflon*Sarda (M*S) and sixteen pure Sarda breed (S*S) suckling lambs were analysed. Chemical and fatty acid composition were determined on semitendinosus and longissimus dorsi muscles and perirenal and pelvic fats. Dressing percentage was higher (P<0.01) in M*S group and after histological dissection M*S carcasses had more muscle tissue (P<0.01) and less separable fat (P<0.05). Muscles of M*S had less cholesterol than the S*S lambs (P<0.01). Polyunsaturated/saturated and n-6/n-3 fatty acids ratios of the intramuscular lipids were optimal in both groups. Indexes of atherogenicity and of thrombogenicity in muscles varied between 0.9 and 1.1. The results indicated several good qualities in both the genotypes, but M*S lambs have some traits which could provide a higher market price. PMID- 22063338 TI - Effects of packaging method and storage time on the chemical, microbiological, and sensory properties of Turkish pastirma - A dry cured beef product. AB - The effects of packaging method (aerobic packaging (AP), vacuum packaging (VP) or modified atmosphere packaging (MAP)), the form of pastirma (sliced or non-sliced) and storage time (0, 15, 30, 60, 90 or 120 days) on the chemical, microbiological and sensory properties of a Turkish pastirma were investigated. Overall, MAP preserved chemical, microbiological and sensory properties of Turkish pastirma better than AP or VP. Very high correlation coefficients (almost all >0.90) were observed between subjective quality parameters (sensory properties) and objective quality parameters (TBARS, hexanal content, L(*), a(*), and b(*)), which suggests that sensory panel was able to determine the quality changes over storage time precisely. Based on the results of this study, MAP should be the preferred choice of packaging in order to preserve overall quality of Turkish pastirma and its implication for pastirma packaging may increase pastirma's current share in the processed meat product market. PMID- 22063339 TI - Effect of processing methods and starter culture (Staphylococcus xylosus and Pediococcus pentosaceus) on proteolytic changes in Turkish sausages (sucuk) during ripening and storage. AB - Proteolytic changes in Turkish sausages (sucuk) produced by two methods (heat processing and traditional) were determined during processing and storage for 90 days. The sausages were produced with or without starter culture in both methods. A mixture of Staphylococcus xylosus and Pediococcus pentosaceus was used as starter culture for their acidic and proteolytic characteristics. The major changes in proteolytic characteristics of sucuk took place during the fermentation stage, with an increase in non-protein nitrogen (NPN) and a decrease in protein solubility. Proteolytic activity was observed in both starter inoculated and non-inoculated (control) sausages during processing. Moreover, a slight increase in proteolytic activity was detected during storage in both starter-inoculated and control traditional sausages, and also in heat-processed sausages due to some heat-resistant proteolytic enzymes. Protein solubility was significantly affected by processing time and heat treatment. Sarcoplasmic and myofibrillar proteins were also affected by starter addition, fermentation, drying and heat processing. During fermentation, starter-inoculated and control sausages showed intense proteolysis in both the traditional and heat processing methods. After heating, intensive degradation of both sarcoplasmic and myofibrillar proteins due to denaturation was observed in heat-processed samples. PMID- 22063340 TI - The relation between glycogen, lactate content and muscle fiber type composition, and their influence on postmortem glycolytic rate and pork quality. AB - This study examined the relation between glycogen, lactate content and muscle fiber type composition, and evaluated their influence on postmortem glycolytic rate and meat quality. Muscle samples were classified based on their glycogen and lactate content at 45min postmortem. Muscles with low glycogen and high lactate levels showed low muscle pH(45min) and high R-values. However, muscles with low glycogen and lactate levels showed normal rates of postmortem glycolysis and normal meat quality. On the other hand, muscles with high glycogen and lactate content showed rapid postmortem glycolysis, paler surface color, higher drip loss, and higher extents of protein denaturation than muscles with high glycogen and low lactate content. These results may be partially explained by muscle fiber type composition. Muscles with low glycogen and lactate content at early postmortem are composed of significantly higher fiber type I and lower fiber type IIB as compared to muscles with high glycogen and lactate content. PMID- 22063341 TI - Comparing the histochemical characteristics and meat quality traits of different pig breeds. AB - The purpose of this study was to compare the muscle histochemical characteristics and meat quality traits between Berkshire, Landrace, Yorkshire, and crossbred pigs. A total of 594 pigs were evaluated. A clear difference between histochemical properties was observed from the results for fiber type composition. In Berkshire pigs, the area percentage of type I fibers was higher (P<0.001) and that of type IIb fibers was lower (P<0.05) than those of other breeds. The muscle pH(45min) and pH(24h) were significantly higher in Berkshire pigs. Drip loss and color parameters were significantly different between the breeds (P<0.001). The Berkshire pigs, which showed the highest muscle pH and lowest drip loss and L(*) values, contained a significantly higher percentage of type I fibers than the other breeds. By comparing the fiber type compositions of the different breeds, the results imply that the longissimus dorsi muscle of Berkshire pigs is more oxidative than that of other breeds. A high pH value in Berkshire pigs is due to a high percentage of type I fibers and a low percentage of type IIb fibers. Based on these results, we conclude that muscle fiber composition can explain in parts the variation of meat quality across and within breeds. PMID- 22063342 TI - The effects of extended curing on the microbiological, physicochemical and sensorial characteristics of Cecina de Leon. AB - The objective of this study was to evaluate the effects of curing times on the characteristics of 7-month dry-cured beef cecina stored for up to 12-months at 16 degrees C and 65% relative humidity. Microbiological and physicochemical parameters, sensorial properties and consumer preferences were analysed at three different processing times (210, 270 and 360days). Curing time significantly affected (p<0.05) most of the parameters studied. Moisture and a(w) decreased (p<0.05) and NaCl content increased from day 210 to day 360, whereas microbial counts decreased (p<0.05) from day 210 to day 360. The continued increase of amino acid content and free fatty acid (p<0.05) until day 360 contributed to modifications in the characteristics of the final product. Thus, cecina with longer processing times had higher scores for colour, flavour and aftertaste. Consumer preferences indicated that the sensory quality of cecina improved from day 210 to day 270 of processing, after which no further changes were noted as curing was extended to 360days. PMID- 22063343 TI - Functional and quality characteristics of the red blood cell fraction from biopreserved porcine blood as influenced by high pressure processing. AB - The effects of high hydrostatic pressure (HHP) processing, at 400MPa for 15min at 20 degrees C, on the microbiological and functional characteristics of the red blood cell (RBC) fraction obtained from porcine blood, previously preserved by means of lactic acid bacteria (LAB) was studied. Biopreservation was achieved by incubation of inulin-enriched blood inoculated with a LAB strain (Enterococcus raffinosus PS99) for 72h at 5 degrees C. Results showed that incubation of blood with added E. raffinosus followed by HHP treatment reduced the levels of contaminant coliforms, proteolytic, hemolytic bacteria, and Pseudomonas spp. on RCB. Color parameters, protein solubility, foaming and emulsifying properties, as well as texture and water holding capacity of heat-induced gels from RBC were not seriously damaged by the combined treatments. This is a new approach to process and preserve animal blood fractions for the development of functional and/or nutritional food ingredients with added value. PMID- 22063344 TI - Breed assignment test in four Italian beef cattle breeds. AB - The assessment of a method able to assign individuals to the breed of origin is needed to certify origin and quality of livestock products. A set of 21 microsatellites was tested for breed identification in four native Italian beef breeds: Chianina, Marchigiana, Romagnola, and Piemontese. Two statistical approaches, based on maximum likelihood and on a Bayesian method, were evaluated. Different marker sets, chosen in order of the highest gene diversity and F(ST) estimates were also tested. The Bayesian method performed better, achieving a correct assignment rate of about 90% even with six microsatellites. The marker sets with the highest gene diversity were shown to perform best. Considering a threshold probability of 90%, only 52.5% of the genotypes were correctly allocated. Such results are mainly due to the low genetic differentiation estimates among breeds (F(ST)=0.049). These findings suggest that markers with high gene diversity and the presence of private alleles should be investigated and the Bayesian method used. PMID- 22063345 TI - How pH causes paleness or darkness in chicken breast meat. AB - Chicken breasts (Pectoralis) at a low-pH (5.91+/-0.12,n=10) were compared with breasts at a high-pH (6.36+/-0.25,n=10,P<0.001). Low-pH breasts had the highest reflectance (P<0.001 from 400 to 700 nm). High-pH breasts had the greatest transmittance into their depth and across individual muscle fibres (P<0.001). The differences in refractive index between ordinary and extraordinary rays across individual muscle fibres were greater in low-pH than in high-pH breasts (P<0.001). Light at low wavelengths had greater reflectance and lower transmittance than light at long wavelengths (P<0.001). Myofibrillar refraction contributed to differences in light scattering between PSE (pale, soft, exudative) and DFD (dark, firm, dry) chicken meat, as it does in pork and beef. PMID- 22063346 TI - Rapid determination of collagen in meat-based foods by microwave hydrolysis of proteins and HPAEC-PAD analysis of 4-hydroxyproline. AB - A rapid microwave procedure for protein hydrolysis coupled with High Performance Anion Exchange Chromatography and Pulsed Amperometric Detection (HPAEC-PAD) was developed to quantify the amino acid 4-hydroxyproline in meat and meat-based products. This innovative approach was successfully applied to determine collagen content (4-hydroxyproline*8) as the index quality of meat material employed in the preparation of typical meat sausages ("Mortadella di Bologna PGI" and "Salamini italiani alla cacciatora PDO") and fresh filled pastas. Microwave hydrolysis showed a precision and accuracy similar to traditional hydrolysis (RSD% from 0.0 to 6.4; relative error 1.4-10.0%) with a reduction in the hydrolysis time from 24h to 20min. HPAEC-PAD allowed detection of 4 hydroxyproline without pre or post-column derivatization and the use of non-toxic eluents. PMID- 22063347 TI - Physico-chemical and microbiological profiles of "salchichon" (Spanish dry fermented sausage) enriched with orange fiber. AB - Spanish dry-fermented sausages with three concentrations (0, 1 and 2%) of orange fiber (juice industry by-product) were prepared and studied. Fermentation and dry curing processes were followed by physico-chemical (pH and water activity), chemical (moisture, lactic acid and residual nitrite level) and microbiological (aerobic mesophilic bacteria, lactic acid bacteria, Enterobacteriaceae, Micrococcaceae and molds and yeasts counts) analysis. Sensory analyses were conducted on the finished products. Only residual nitrite level and counts of micrococcus were affected by fiber addition during fermentation. pH, water activity, residual nitrite level and counts of Micrococcaceae were affected by fiber addition during dry-curing. Orange fiber decreases residual nitrite levels and favours micrococcus growth. Both effects have a positive impact on sausage safety and quality. The reduction in residual nitrite level decreases the risk of nitrosamine formation. For all sensorial attributes evaluated sausages containing 1% fiber showed similar scores to controls. PMID- 22063348 TI - Microbial profiles of frozen trimmings and silver sides prepared at Indian buffalo meat packing plants. AB - To assess microbiological quality of buffalo meat trimmings (TT=114) and silver sides (SS=41), samples were collected from four different Indian meat packing plants. The aim of this study was: (i) to evaluate standard plate count (SPC), psychrotrophic count (PTC), Enterococcus feacalis count (EFC), Staphylococcus aureus count (SAC) and Escherichia coli count (ECC) and the presence of Salmonella spp. and Listeria monocytogenes; and (ii) also to determine vero toxic E. coli (VTEC) by polymerase chain reaction (PCR). TT samples had significantly higher (P<0.001) SPC, PTC, EFC, and SAC than SS, while across the meat types there was no difference (P>0.05) in ECC. E. coli was recovered from 32.4% TT and 19.5% SS samples. The prevalence rate of Salmonella spp. and L. monocytogenes in TT was 1.75% and 0.87%, respectively. But no SS sample was found to be positive for any of these two pathogens. VTEC was found in 2.58% of all the tested samples. This finding suggests that TT contain higher microbes but only small numbers of pathogens of latent zoonotic importance. The present study confirmed the importance of maintaining good process hygiene at meat plants for microbiological status of buffalo meat. PMID- 22063349 TI - De electricitatis catholici musculari - Concerning the electrical properties of muscles, with emphasis on meat quality. AB - This study aims to explore the potential of evoked non-invasive surface electromyography (SEMG) analysis, in predicting meat quality traits in livestock. Evoked SEMG is a system that records, transdermally, electrical signals generated in muscle fibres upon external stimulation. These signals are reported as compound muscle action potentials (CMAP). CMAP parameters of LD correlated negatively and significantly to ultimate pH (pH 24h) at day 61, but not at day 153 after birth, and a similar albeit positive correlation was observed for muscle glycogen content. Muscle glycogen content and pH 24h correlated negatively in LD and BF. Negative significant correlations between CMAP parameters and shear force were found in LD at day 153 after birth, which might, in the range of the recording electrodes, reflect the combined effect of large cross-sectional area fibres and reduced perimysium content per unit volume of muscle. The fact that correlations between CMAP characteristics and quality traits of both metabolic and non metabolic origin could be established, warrants a fuller investigation of this method in terms of its potential as a predictive tool for meat quality traits in live animals. PMID- 22063350 TI - Changes in fatty acids and polar material of restructured low-fat or walnut-added steaks pan-fried in olive oil. AB - The study aims to determine the influence of pan-frying on the fatty acid composition and fat content and alteration of functional restructured beef steaks. Low-fat (L, 2% fat), 20% walnut-added (W, 13% fat) and medium fat (M, 13% fat) steaks were prepared and fried in extra virgin olive oil. Pan-frying increased fat in L and W steaks and decreased it in M ones. Raw L and M steaks showed similar fatty acid profiles while W ones contained a lower percentage of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) but a higher percentage of polyunsaturated fatty acids (PUFA). The fatty acid profile of fried steaks was between that of the raw steaks and olive oil. Several fatty acids (g fatty acid/100g edible steaks) were affected (p<0.001) by the frying*meat formulation interaction. Linoleic and linolenic acid contents did not decrease in fried W steaks, but decreased (p<0.05) when data were expressed on a dry matter basis. Frying increased SFA, MUFA and omega-6 PUFA contents in L samples while it decreased SFA and increased omega-6 PUFA in M steaks. Before and after frying, W steaks had atherogenic and thrombogenic indexes at least three times lower than their counterparts. Both indexes decreased in fried L samples while only the AI in M ones. Polar material content (PM) increased only in L samples. No relevant differences were found between PM of the fried steaks and that of their corresponding used oils. Results suggest that pan-frying improves the fatty acid composition of L and M steaks with minor changes in PM. The high retention of lipids observed in the W samples permits consumption of omega-3 PUFA- and omega-6 PUFA-enriched meat with a very low content of alteration compounds. PMID- 22063351 TI - Effect of pre- and post-pubertal castration on Piemontese male cattle. II: Carcass measures and meat yield. AB - The effect of different castration ages on carcass morphological characteristics, meat yield, commercial cuts and bones weight and measures was evaluated on Piemontese steers and bulls. Carcasses (24) obtained from early castrated (EC, 5th month of age), late castrated (LC, 13th month) and intact males (IM, control group) of similar age (about 18 months) and fattening degree, were weighed, measured and dissected following the local commercial method. Very few differences were found in carcass conformation and fatness as in carcass weight and measures. After data adjusting, few meat cuts were heavier in IM compared to EC and LC, and only one cut measure was different, whereas, almost no differences were found in bone measures and weight. IM produced carcasses with more edible meat than LC and more forequarter and 2nd quality meat than LC and EC. Significant differences were found also between total, hindquarter and perinephric fat. PMID- 22063352 TI - Polycyclic aromatic hydrocarbons (PAHs) in different types of smoked meat products from Serbia. AB - The contents of the16 EU priority PAHs in six different meat products from Serbia (beef ham, pork ham, bacon without skin, bacon with skin, cajna sausage and sremska sausage) were examined during the process of smoking. All these meat products from meat industry Zlatiborac, Mackat, Serbia presented in this study, have not previously been analysed concerning to their contents of PAH compounds. Determination and quantification of PAHs in meat products were performed by a Fast GC/HRMS method. The maximum level for benzo[a]pyrene (BaP) of 5MUg/kg in smoked meat products was not exceeded in any samples. BaP comprises in general 4.6% of the total sum of the 16 EU priority PAHs and 15.2% of the total sum of the 12 IARC PAH compounds. The suitability of BaP as a marker both for 16 EU priority PAHs and 12 IARC probably and possibly carcinogenic PAHs was checked by applying correlation analysis. PMID- 22063353 TI - Effect of freezing on sensory quality, shear force and water loss in beef M. longissimus dorsi. AB - The objective of this study was to determine how sensory quality, shear force and water loss differ between beef stored either chilled or frozen before cooking. Meat tenderness was analysed instrumentally and sensorially using both a consumer panel and a semi-trained panel. Both M. longissimus dorsi (LD) from eight young Holstein bulls were cut into eight samples, weighed, vacuum packed and aged at 4 degrees C for 2, 7 or 14 days. After ageing, the frozen samples were kept at -20 degrees C prior to heat treatment. Water holding capacity was recorded as purge or thawing loss and cooking loss or as combined loss. Sensory analyses were performed on samples aged 7 days. Peak force values declined with ageing time and freezing. Frozen meat aged 2 days had the same peak force values as chilled meat aged 7 days. Total energy was the same for both treatments at day 2 and 7, whereas at day 14 frozen samples showed significantly higher values than chilled samples. The sensory panel experienced the chilled meat to be more tender, juicier and having a more intense meat taste than the frozen meat, whereas the consumers could not find any significant difference in degree of liking. Water holding capacity was lower for the frozen samples. The results indicate that conclusions from studies concerning sensory quality of beef will depend on whether the meat has been kept chilled or frozen before testing. PMID- 22063354 TI - Study of the Lactobacillus sakei protective effect towards spoilage bacteria in vacuum packed cooked ham analyzed by PCR-DGGE. AB - The effectiveness of Lactobacillus sakei B-2 inoculated as a protective culture on the inhibition of spoilage bacteria on sliced vacuum packed cooked ham was investigated by using culture-dependent and -independent approaches. Total microbial DNA was directly extracted from both control and treatment samples, and subjected to a nested PCR protocol, PCR-DGGE analysis was used to identify and monitor the dynamic changes in the microbial population, followed by partial 16S rDNA sequencing. The DGGE profile demonstrated that the protective culture effectively suppressed growth of predominant spoilage bacteria L. sakei, Lactobacillus curvatus and Leuconostoc mesenteroides in cooked ham during storage at 4 degrees C, however, growth of uncultured Leuconostoc was not inhibited. The shelf-life of this product inoculated with L. sakei B-2, at levels of 5.91+/ 0.04log(10)CFUg(-1) was 35 days, compared to 15 days of control samples, when the ham was stored at 4 degrees C. PMID- 22063355 TI - Composition and quality differences between the longissimus and infraspinatus muscles for several groups of pasture-finished cattle. AB - Samples of longissimus (LT) and infraspinatus (IS) muscles from five contrasting groups of pasture-finished cattle (n=7/group) were assessed for quality and composition characteristics in order to determine whether features of pasture finished beef reported previously apply across different muscles and different classes of cattle. The cattle were not raised together or slaughtered at the same time. Wagyu-cross steers had the highest intramuscular fat levels, particularly in the LT, followed by Angus steers, Charolais-cross steers and Belgian Blue cross steers, with the lowest levels for Friesian bulls. Relative to the LT, the IS muscle had longer sarcomeres, higher cooking losses, higher concentrations of vitamin E, and lower myofibrillar fragmentation indexes, while its ultimate pH was slightly higher but less variable. Beef from Wagyu-cross steers had the highest chroma values and the lowest shear values, while Friesian bull beef was darkest and least tender. Intramuscular fatty acid composition and concentrations of bioactive compounds such as coenzyme Q(10) and carnosine, were similar to those reported previously for cattle finished on New Zealand pastures although taurine levels were lower. Generally concentrations of bioactive compounds differed more between muscles and groups than between cattle finished on pasture or grain as reported previously. PMID- 22063356 TI - Microbial and physicochemical succession in fermented sausages produced with bacteriocinogenic culture of Lactobacillus sakei and semi-purified bacteriocin mesenterocin Y. AB - The influence of the bacteriocinogenic culture Lactobacillus sakei (10(5)/g) and semi-purified bacteriocin mesenterocin Y (2560AU/kg) on the safety and quality of traditional Croatian fermented sausages was investigated. The addition of Lb. sakei and/or mesenterocin Y reduced microbial counts (P<0.05) in the final products. After 28 days of ripening, coagulase-negative cocci decreased 1.5 2.0log, yeasts 1.2-1.4log and enterococci 1.7-2.7log. In the case of the addition of Lb. sakei, the lactic acid bacteria count was significantly (P<0.05) higher at day 7 of ripening, and was accompanied by a lower pH and a higher amount of lactic acid (P<0.05). In the final product the amount of acetic acid was significantly lower. More intensive proteolysis and an increase in ammonia content were found at the beginning of fermentation, and in the second phase of ripening in the control samples, respectively. The free fatty acid concentration was significantly lower during the entire ripening process compared to the control (P<0.05). Semi-purified mesenterocin Y did not affect the sensory properties of the sausages, whilst the addition of Lb. sakei enhanced them. PMID- 22063357 TI - A comparison of conventional and radio frequency tempering of beef meats: Effects on product temperature distribution. AB - This study aimed to develop radio frequency (RF) pilot-scale protocols for tempering beef meat blends (4kg blocks) to achieve average temperatures between 2 and -5 degrees C. Post-tempering temperature distribution in these blocks was compared to products tempered by conventional methods. The optimum RF power-time combination for tempering lean and 50:50 lean:fat mixtures to the target range was 500W for 11min which produced respective means of -3.6 degrees C (s.d. 1.1) and -3.4 degrees C (s.d. 1.5). In contrast, 400W for 11min was optimum for fat (mean -4.9 degrees C, s.d. 2.1). This study shows the principal advantages of RF over conventional tempering as an approximate 30 fold tempering time reduction and a greater uniformity of end point temperature distribution under the conditions employed. Furthermore, power consumption was reduced approximately ninefold with RF compared to conventional tempering. More uniform temperature distribution was achieved in samples that were comminuted to a greater extent. PMID- 22063358 TI - Partial replacement of pork fat by conjugated linoleic acid and/or olive oil in liver pates: Effect on physicochemical characteristics and oxidative stability. AB - The effect of replacing pork fat in liver pates by an enriched conjugated linoleic acid oil (CLA-pate), olive oil (OO-pate), or the combination of both type of oils (CLA+OO-pate) on the fatty acid profile, lipid oxidative stability, consistency and emulsion stability was studied and compared with a traditional liver pate (C-pate). Pates were analyzed at days 1, 6, 21 and 71 of refrigerated storage (4 degrees C). A enrichment in CLA was attained in CLA-pate and CLA+OO pate. CLA-pates had the highest content in polyunsaturated fatty acids (PUFA) (p<0.05) due to their content in CLA. A lower content in saturated fatty acids was achieved when using OO or CLA in pates (p<0.05). OO-pates showed the highest levels of monounsaturated fatty acids (MUFA) (p<0.05). No changes in the fatty acid profile and in lipid oxidation (mg malondialdehyde per kg of sample) throughout the storage of the products were found. Lower consistency and emulsion stability were obtained when using CLA or OO in the formulation. Consistency values (in N/cm(2)) tended to increase and emulsion stability to decrease throughout the storage in CLA or OO enriched pates. PMID- 22063359 TI - Characteristics of Staphylococcus hyicus strains isolated from pig carcasses in two different slaughterhouses. AB - In a previous study, we showed that coagulase positive staphylococci, which are often used as indicators for Staphylococcus aureus, are frequently found on pig carcasses. Further characterization of the strains identified only a minor part as S. aureus. Selected non-S. aureus strains were all identified as Staphylococcus hyicus, However, two studies described in this species strains that produce staphylococcal enterotoxins. The aim of the present study was to further characterize such coagulase positive S. hyicus strains isolated from pig carcasses and to assess the results for their food safety relevance. A total of 189 strains from two abattoirs were characterized. Phenotypically, 98.9% showed non-pigmented colonies, 99.5% no haemolysis and 67.7% were egg yolk-positive. DNase activity was found in all but one isolate. Only five of the 189 strains were resistant to the antimicrobials tested. One strain harboured the mecA gene. Exfoliative toxin genes were detected in 31 (16.4%), S. aureus enterotoxin genes in none of the strains. The PFGE genotyping results show only a limited number of clusters. Cluster I included more than 50% of the strains. The fact that similar or closely related PFGE patterns of S. hyicus can be found on carcasses after bleeding in both abattoirs indicates the occurrence of widespread strains in the Swiss pig population. Moreover, the genotyping results revealed a remarkable homogeneity in S. hyicus strains isolated from different process stages in abattoir B, which could indicate a recontamination problem with persisting strains. PMID- 22063360 TI - Inhibition of nitric oxide release pre-slaughter increases post-mortem glycolysis and improves tenderness in ovine muscles. AB - The aim of this experiment was to determine the effect of inhibiting the release of nitric oxide (NO) pre-slaughter in lambs on post-slaughter muscle metabolism and meat quality. Exercise was used as a positive control as NO is known to be released in skeletal muscle during exercise. Forty Border Leicester*Merino lambs were assigned to the treatments L-NAME (NO synthase inhibitor) infusion (0mg/kg vs. 30mg/kg, 135min pre-slaughter) and exercise (none vs. 15min immediately pre slaughter). The inhibition of NO release using L-NAME reduced Warner-Bratzler shear force (WBSF) in the longissimus thoracis et lumborum (LTL) after 3days of ageing, while the Semimembranosous (SM) was unaffected. Inhibition of NO release with L-NAME resulted in altered glucose metabolism as indicated by reduced plasma glucose pre-slaughter particularly in exercised lambs, reduced LTL and SM glycogen of non-exercised lambs post-slaughter and increased SM lactate in exercised lambs post-slaughter. In conclusion, inhibition of NO Synthase with L NAME pre-slaughter increases post-mortem glycolysis and improves tenderness in the loin muscle. PMID- 22063361 TI - Production performance and meat quality characteristics of sheep comprising four sex-types over a range of slaughter weights produced following commercial practice. AB - Eighty four lambs comprising four sex-types (entire rams, castrated rams, vasectomised rams and entire ewes) were distributed equally into seven target slaughter weights (32, 36, 40, 44, 48, 52 and 56kg). All lambs were born in early spring. Dams and lambs were out on pasture until late September when they were housed and fed concentrate and hay. At birth, ram lambs were heavier than ewe lambs (P<0.01) and gained weight faster (P<0.05). The three male sex-types were similar in birth weight, growth rate and dressing out percentage (P>0.05), and were significantly lower than ewes in dressing out percentage (P<0.001). The m. longissimus dorsi (LD) from all sex-types were similar in initial pH, ultimate pH and sarcomere length (P>0.05) but differed in cooking loss and shear force (P<0.05). The LD from ewes were lower in cooking loss than those from the male sex-types (P<0.05), and recorded smaller shear force values (P<0.05). The average a(*) values (redness) of the LD was highest in ewes and differed only from that of vasectomised rams (P<0.05). Ewes were also highest in oxymyoglobin proportion (P<0.05). Although correlations between most meat quality parameters and slaughter weight were highly significant (P<0.001) the correlation coefficients (r) were generally small. PMID- 22063362 TI - Effect of the Iberian pig line on dry-cured ham characteristics. AB - The purpose of this study was to compare the characteristics (chemical composition, instrumental colour, sensory characteristics and acceptance) of dry cured hams obtained form three genetic lines of Iberian pig (Censyra, Torbiscal and Entrepelado). The instrumental colour of fat was affected by the genetic line (b(*), p=0.008; and h degrees , p=0.024), the Censyra group having the largest values. The genetic line did not affect the chemical composition of the subcutaneous fat and lean of the dry-cured hams or the instrumental colour of the lean. Data from a descriptive analysis showed that the only characteristic significantly affected was the toasted flavour (p=0.004), and juiciness and sweetness were slightly affected (p=0.062 and 0.061, respectively). In spite of the slight effect on the physical-chemical and sensory characteristics, acceptance was significantly different, Torbiscal hams having the highest scores. PMID- 22063363 TI - Hydrolyzed wheat gluten suppresses transglutaminase-mediated gelation but improves emulsification of pork myofibrillar protein. AB - The influence of 15-h chymotrypsin-hydrolyzed wheat gluten (GH) on microbial transglutaminase (MTGase)-mediated interaction, gelation and emulsification of pork myofibrillar protein isolate (MPI) was investigated at two ionic strengths (0M and 0.6M NaCl) and pH 6.5. MTGase treatments in 0M NaCl solution decreased the size of myosin heavy chain through deamidation, but this was inhibited by GH or in 0.6M NaCl where myosin polymerization dominated. Stabilization of MPI (thermal transitions) by the MTGase treatment was also diminished (P<0.05) by the presence of GH at both ionic strengths. These GH-induced MPI physicochemical changes greatly weakened the ability of MTGase to promote MPI thermal gelation (gel storage modulus, P<0.05), especially at 0.6M NaCl, which was shown to result from reduced protein aggregation. However, GH improved (P<0.05) emulsifying properties of MPI, regardless of MTGase treatment. PMID- 22063364 TI - Determination of changes in protein conformation caused by pH and temperature. AB - Protein denaturation has a major impact on meat quality parameters such as water holding capacity, tenderness and color. Specific information about structural changes of the individual muscle proteins post-mortem could help understand the factors affecting meat quality. An aromatic dye, 4,4'-dianilino-1,1'-binaphthyl 5,5'-disulfonic acid (bisANS) that binds to the hydrophobic patches of proteins was used to monitor changes in the conformation of individual sarcoplasmic proteins caused by pH. The bisANS reagent was covalently linked to the proteins with UV-light and the proteins were separated and identified using gel electrophoresis and mass spectrometry. The results showed that the sarcoplasmic proteins creatine kinase M, aldolase A and lactate dehydrogenase showed increased hydrophobicity whereas carbonic anhydrase III showed decreased hydrophobicity with increasing pH. Temperature only had a marked effect on the results at around 40 degrees C, there being no change between 25 and 35 degrees C. PMID- 22063365 TI - Effects of growth rate, sex and slaughter weight on fat characteristics of pork bellies. AB - A total of 119 Duroc*(Landrace*Yorkshire) commercial pigs were used to investigate the effect of growth rate (fast vs slow), sex (barrows vs gilts) and slaughter liveweight (107, 115 and 125kg) on the fat characteristics of bellies. Backfat thickness increased with weight (P<0.01). Fat firmness score was only affected by sex (P<0.05), with gilts showing softer bellies than barrows. Fat from gilts and slow growing pigs showed a lower proportion of saturated fatty acids (SFA; P<0.001 and P<0.01, respectively), a higher proportion of linoleic fatty acid (C18:2 n-6; P<0.01), a higher proportion of total polyunsaturated fatty acids (PUFA; P<0.001 and P<0.01, respectively), and an increased iodine value (P<0.001). Consequently, the fat from these bellies had higher PUFA:SFA ratios (P<0.001) and n-6:n-3 ratios (P<0.01 and P<0.001, respectively) than that from the bellies of barrows and fast growing pigs. The belly fat from barrows and fast growing pigs had higher stearic fatty acid (C18:0; P<0.01) and SFA proportions (P<0.001 and P<0.01, respectively) than that from gilts and slow growing pigs. The belly fat from gilts and slow growing pigs would better meet the health requirements of consumers, but it is more prone to rancidity during storage leading to a potentially reduced bacon shelf-life. PMID- 22063366 TI - The changes of signal transduction pathways in hippocampal regions and postsynaptic densities after chronic cerebral hypoperfusion in rats. AB - The mechanisms underlying the cognitive impairment after chronic cerebral hypoperfusion (CCH) are not fully clarified. In the present study, we investigated the molecular basis for the cognitive deficits under the condition of CCH in rats. The ultrastructural changes of postsynaptic densities (PSDs) were examined by ethanolic phosphotungstic acid (EPTA) electron microscopy. Various protein kinase phosphorylation/dephosphorylation levels of the signal transduction pathways in hippocampal regions and postsynaptic densities were assessed by Western blotting. On EPTA electron microscopy, we demonstrated that proteins were highly aggregated in PSD structures of the hippocampal CA1 areas in rats at 3 months after CCH. By Western blotting, the model rats exhibited significant decrease in the levels of hippocampal Ca(2+)-calmodulin-dependent protein kinase II (CaMKII), phospho-CaMKII (p-CaMKII), phospho-extracellular regulated kinase (p-ERK), PSD CaMKII and p-ERK, with no corresponding changes in the levels of phosphorylation/dephoosphorylation protein kinase A (PKA) and protein kinase C (PKC). These results suggest that both the ultrastructural changes of PSDs and aberrant signal transduction may be involved in CCH-induced alterations in synaptic transmission underlying the cognitive dysfunction in rats of CCH. PMID- 22063367 TI - Hospital-associated infections in children: a prospective post-discharge follow up survey in three different paediatric hospitals. AB - BACKGROUND: Reported viral hospital-associated infection (HAI) frequencies have ranged from 1% to 24% between paediatric wards and hospitals. Reasons for this variation remain unclear. AIM: To evaluate the rate of viral HAIs and risk factors in three different paediatric hospitals. METHODS: Data were collected prospectively for two years in one infectious disease ward and three general paediatric wards in Finland and Switzerland. Infections were recorded during the hospitalization and one week after discharge. Ward-specific risk factors for HAIs within each ward were searched by using multivariate logistic regression analysis. FINDINGS: Altogether 5119 patients were hospitalized. Total HAI frequency was 12.2%, with 2.4% of the patients developing HAI in hospital, most often gastroenteritis, and 9.8% [95% confidence interval (CI): 8.9-10.8%] within 72 h of discharge. HAI rates varied from 5.8% to 17.1% between the wards, the highest rate being in a general paediatric ward where shared rooms were common and active cohorting according to viral aetiology was not done. Shared room (OR: 5.45; 95% CI: 2.44-12.2 in a general ward treating infants), longer hospitalization (OR: 1.42 per day; 95% CI: 1.20-1.67 in an infectious disease ward) and young age (OR: 0.71 per year; 95% CI: 0.51-0.98 in general paediatric ward for children aged >1 year) increased risk of HAI in hospital. CONCLUSION: Most viral HAIs in paediatric wards become evident after discharge. Single room bedding appears to be effective in preventing HAIs, especially the spread of respiratory viruses. It also appears that caring for patients with contagious diseases in a separate unit is advantageous. PMID- 22063368 TI - Defining osteoarthritis: a moving target. PMID- 22063369 TI - Global metabolic profiling of human osteoarthritic synovium. AB - Osteoarthritis (OA) is a debilitating disease associated with pain and loss of function in numerous diarthrodial joints of the body. Assessments of the severity and/or progression of OA are commonly based on radiographic stages and pain level, which aren't always correlated to severity of disease or joint dysfunction and may be confounded by other factors(1). There has been recent interest in identifying a biochemical signature of OA(1) that may be detected in serum, urine, and/or synovial fluid that would represent repeatable and predictable biomarkers of OA onset and/or progression. The objective of this study was to use global metabolic profiling to identify a distinct metabolic profile for cultured human synovial tissue from patients with end-stage OA compared to patients with little or no evidence of disease. While metabolic profiles from cultured tissues are not expected to reproduce in vivo profiles, it is expected that perturbations in metabolism caused by end-stage disease would result in differences in metabolic profiles in vitro compared to tissue with little or no evidence of disease. Because metabolomic perturbations often occur prior to alterations in the genome or proteome, metabolomic analysis possibly provides an earlier window to an altered biochemical profile for OA onset and/or progression, and may provide a unique set of potential drug targets. The synovium was targeted because it has been implicated in OA as a mediator of disease progression; osteoarthritic synovium has been demonstrated to express pro-inflammatory cytokines, such as Tumor Necrosis Factor - alpha (TNF-alpha), Interleukin-1 beta (IL-1beta), and IL 6(2), suggesting that a diseased synovial lining could produce an ideal set of biomarkers for diagnosing OA and/or monitoring disease progression. Media from the culture of synovial explants dissected from diseased human joints (early or end-stage OA) was subjected to global metabolic profiling with a liquid chromatography (LC)/and gas chromatography (GC)/mass spectrophotometry (MS)-based technology platform. Metabolites were identified by automated comparison of the ion features in the experimental samples to a reference library of chemical standard entries developed at Metabolon, Inc (Durham, NC). Global metabolic profiling resulted in the identification of 105 distinct compounds across all sample groups, with 11 compounds showing significantly different relative concentrations between end-stage and no/early disease groups. Metabolites specific to collagen metabolism, branched-chain amino acid metabolism, energy metabolism and tryptophan metabolism were amongst the most significant compounds, suggesting an altered metabolic state with disease progression. PMID- 22063370 TI - Methadone and morphine during anesthesia induction for cardiac surgery. Repercussion in postoperative analgesia and prevalence of nausea and vomiting. AB - BACKGROUND AND OBJECTIVES: Pain is an aggravating factor in postoperative morbidity and mortality especially in large size surgeries. Methods to effectively fend pain collide with elevated costs and for this reason they are not accessible in every service. The option would be the use of an opioid with long half-life, such as methadone. The objective of the present study was to compare the requirements of postoperative analgesia in patients who received methadone, morphine, or placebo during anesthetic induction, besides the prevalence of postoperative nausea and vomiting. METHODS: Fifty-five patients scheduled for cardiac surgery were divided into three groups and they received during anesthetic induction 20mg of methadone, 20mg of morphine, or placebo. At the end of surgery, patients were transferred to the ICU where the following parameters were evaluated: duration of anesthesia, time until extubation, time until the need of the first analgesic, number of doses required in 24 hours, assessment of analgesia by the patient, and prevalence of nausea/vomiting. RESULTS: Differences in the duration of anesthesia and time until extubation were not observed. The first dose of analgesic in patients who received methadone was administered later than in patients in the other two groups. The need of analgesics in the methadone group was lower, quality of analgesia was better, and prevalence of nausea and vomiting was also lower. CONCLUSIONS: Methadone during anesthetic induction was effective for analgesia in large size surgeries. Lower incidence of nausea and vomiting was observed in the methadone group and therefore it is a low cost option available among us that should be stimulated. PMID- 22063371 TI - Citrus aurantium blossom and preoperative anxiety. AB - BACKGROUND AND OBJECTIVES: Reducing anxiety is very important before operation. Preoperative visit and use of premedication are popular methods to achieve this goal, but the role of anxiolytic premedication remains unclear and postoperative side-effects may result from routine premedication. Citrus aurantium is used as an alternative medicine in some countries to treat anxiety, and recently the anxiolytic role of this medicinal plant was established in an animal model study. The aim of this study was to assess the anxiolytic effect of Citrus aurantium blossomon preoperative anxiety. METHODS: We studied 60 ASA I patients undergoing minor operation. In a randomized double-blind design, two groups of 30 patients received one of the following oral premedication two hours before induction of anesthesia: 1) Citrus aurantium blossom distillate 1mL.kg(-1) (C-group); 2) Saline solution 1mL.kg(-1) as placebo (P-group). Anxiety was measured before and after premedication using the Spielberger state-trait anxiety inventory (STAI state) and the Amsterdam preoperative anxiety and information scale (APAIS) before operation. RESULTS: After premedication, both the STAI-state and the APAIS scales were decreased in C-group (p<0.05); while exhibiting no significant changes in P-group. CONCLUSIONS: Citrus aurantium blossom may be effective in terms of reduction in preoperative anxiety before minor operation. PMID- 22063372 TI - The influence of posture on spirometric values in grade III obese patients. AB - BACKGROUND AND OBJECTIVES: The change from the sitting position to supine position, general anesthesia, and surgical procedure reduce lung volumes and this effect can be greater in obese patients. The objective of the present study was to evaluate the influence of the sitting position, 30 dorsal inclination, and horizontal dorsal decubitus on spirometry of grade III obese patients. METHODS: Twenty-six adult patients in the preoperatory period were selected according to the following criteria: BMI>40kg.m(-2), age between 18 years and 60 years, and female gender. Variables analyzed included: age, weight, height, BMI, percentage of predictive values of FVC, FEV(1), and VEF(1)/FVC in the sitting position (90 degrees ), 30 degrees dorsal elevation, and horizontal dorsal decubitus (0 degrees ). ANOVA, followed or not by Tukey test were used to compare mean predicted values on the different positions, considering significant a p value lower than 0.05. RESULTS: Percentage values of FVC, FEV(1), and FEV(1)/FVC ratio regarding predicted values in the sitting position (90 degrees ), 30 degrees dorsal elevation, and horizontal dorsal decubitus (0 degrees ), and p value of the corresponding statistical analysis were, respectively: FVC=92.8%, 88.2%, and 86.5%, p=0.301 (ANOVA); FEV(1): 93.1%, 83.8%, and 83.3%, p=0.023 (ANOVA), p=0.038 (Tukey test - 90 degrees *0 degrees ); FEV(1)/FVC: 100,8%, 95.5%, and 96.8%, p=0.035 (ANOVA), p=0.035 (Tukey test - 90 degrees *30 degrees ). CONCLUSIONS: Changes in position produced changes in spirometry results of patients with grade III obesity. PMID- 22063373 TI - What do patients know about the work of anesthesiologists? AB - BACKGROUND AND OBJECTIVES: Modern international studies portray the lack of knowledge of patients regarding the education and role of anesthesiologists. There are no current data on this subject in the national scenario. The objective of this study was to assess the level of knowledge of patients about the education and areas of performance of these specialists. METHODS: This is a prospective study undertaken at a tertiary university hospital in Sao Paulo. During an 18-month period preoperative patients were interviewed. The data were analyzed by the Fisher's exact test, Chi-square test, and Mann-Whitney test according to the variable investigated. In the study, an alpha risk<=0.05 of making a type I error was considered. RESULTS: Four hundred patients, 203 (50.75%) males and 197 (49.25%) females, aged between 18 and 89 years were included in this study. A total of 207 patients (51.75%) recognized anesthesiologists as physicians. Two hundred and eighty-nine (72.25%) patients answered that anesthesiologists care for patients during surgeries, while 256 (64%) did not know that anesthesiologists determine whether patients are fit to undergo surgery. A statistical correlation was observed between the level of schooling and the presence of prior experience with anesthetic-surgical procedures and the correct response to the medical education of anesthesiologists. A significant difference was not observed between the group of patients who underwent pre-anesthetic evaluation and those that did not undergo the evaluation regarding the knowledge of the medical education of anesthesiologists. CONCLUSIONS: A large proportion of patients have a limited knowledge about the education and role of anesthesiologists. Pre-anesthetic evaluation did not increase the proportion of answers that anesthesiologists have medical education. PMID- 22063374 TI - The efficacy of terlipressin versus adrenaline in swine cardiopulmonary resuscitation. AB - BACKGROUND AND OBJECTIVES: The objective of the present study was to evaluate the efficacy of terlipressin (TP) vs. adrenaline (ADR) in increasing coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC) in swine CPR. METHODS: Under anesthesia with ketamine/thiopental, ventricular fibrillation was induced in 44 female immature pigs, remaining unassisted for 10 minutes, followed by 2 minutes of manual CPR (100 compression/10 ventilations/min with air). Animals were, then, divided into four groups: 1) ADR (45MUg.kg(-1)); 2) saline-placebo (10mL); 3) TP 20MUg.kg(-1)); and TP (20MUg.kg(-1)) + ADR (45MUg.kg(-1)). Defibrillation was performed after 2 minutes, observing surviving animals for a 30-minute period. Electrocardiogram, systemic BP, DBP, and PetCO(2) were monitored continuously. RESULTS: Terlipressin did not differ from placebo regarding the effects on CPP, with low rates of ROSC in both groups (1/11 vs. 2/11; p=NS). Adrenaline increased CPP from 13+/-12 to 54+/-15mmHg (p<0.0001), similar effect to TP + ADR (from 21+/-10 to 45+/-13mmHg; p<0.0001), with high rates of ROSC/survivors in both groups (10/11 vs. 9/11, respectively). Among survivors, greater MAP was observed in the TP + ADR group vs. ADR (105+/-19mmHg vs. 76+/-21mmHg; p=0.0157) groups. CONCLUSIONS: Adrenaline and TP + ADR were effective on maintaining CPP/ROSC in this experimental model, but isolated TP did not differ from placebo. However, in surviving animals in the TP + ADR group, greater hemodynamic stability was observed after ROSC, suggesting that TP can be a useful medication in the management of post-CPR hypotension. PMID- 22063375 TI - Assessing the use of 50% enantiomeric excess bupivacaine-loaded microspheres after sciatic nerve block in rats. AB - BACKGROUND AND OBJECTIVES: To achieve better therapeutic benefits of local anesthetics in the control of postoperative pain through controlled-release carrier. The objective of this study was to compare the characteristics of sensory and motor blockade between microspheres without local anesthetic: racemic bupivacaine-loaded microspheres; 50% enantiomeric excess bupivacaine-loaded microspheres; and free 50% enantiomeric excess bupivacaine. METHODS: Wistar rats were distributed into four groups: A (Microsphere); B (S50-R50 bupivacaine-loaded microsphere); C (50% enantiomeric excess bupivacaine-loaded microsphere); and D (50% enantiomeric excess bupivacaine). Inhalation anesthesia was performed before the sciatic nerve block (2% halothane and 100% O(2)). Sensorial blockade was measured by the time required for each rat to withdraw its paw from a hot plate at 56 degrees C (positive>4 sec). Motor blockade was measured by the time between drug injection until recovery of a motor score of 2 on the established criterion. RESULTS: The sensory response was significantly more frequent in groups B, C, and D than in group A (p<0.001). There were no statistically significant differences in the response to the sensory test in groups B, C, and D (p>0.05). The response to the motor test was also significantly more frequent in groups B, C, and D than in group A (p=0.02). A tendency to greater positivity in the motor test was more frequently found in groups B and D than in group C (p=0.10). CONCLUSIONS: Controlled-release of 50% enantiomeric excess bupivacaine-loaded microspheres showed similar results regarding analgesia and less motor blockade when compared to other anesthetic formulations. PMID- 22063376 TI - Myasthenia gravis: two case reports and review of the literature. AB - BACKGROUND AND OBJECTIVES: Myasthenia gravis (MG) is an autoimmune neurologic disease that affects the postsynaptic portion of the neuromuscular junction. It represents a challenge for anesthesiologists due to the diversity of disease manifestations and possibility of postoperative respiratory complications. The objective of this study was to demonstrate the importance of adequate monitoring of the neuromuscular blockade (NMB) due to the multiple presentations of MG. CONTENTS: In this paper we report two cases of patients with MG. The first patient presented with the classical sensitivity to the neuromuscular blocker (NMB) and the second had a similar response to that of a normal patient. The literature review will be restricted to disease characteristics, while the description of its pathophysiology will focus on its reactions to NMB. CONCLUSIONS: We suggest that, due to the multiple presentation and treatment of MG, neuromuscular transmission monitors are fundamental when using NMB. PMID- 22063377 TI - Cephalad angulation of epidural needle insertion may be an important factor for safe epidural space approach: a mathematical model. AB - BACKGROUND AND OBJECTIVES: Epidural approach angle is one of the determining factors for needle traveling length to reach the epidural space. Likewise, the margin of safety against accidental dural puncture should be affected by epidural approach angle because the space available for epidural needle tip movement in the epidural space is depending on the inserting angle to the epidural space. The purpose of this study is to conjecture the effect of the angle formed with the skin and an epidural needle on the margin of safety against accidental dural puncture using a mathematical model. CASE REPORT: Suppose that the width of the epidural space is A mm and that the force advancing the epidural catheter is Ckgf and the diameter of the catheter is D mm. In this situation, assuming that the cephalad angle with the midline approach formed with the skin and an epidural needle is theta, the following parameters can be determined: the available distance for the needle tip in the epidural space = A/sinthetamm; cephalad advancing force of catheter = C*costhetakgf; and the pressure at the site of dura matter where the epidural catheter is pushing = 400*C*sintheta.piD(-2)kgf.cm(-2). The longer the distance available for the needle tip, the larger the margin of safety for dura injury by the epidural needle. It is supposed that theta should be set smaller to make the margin of safety larger. Likewise, smaller theta could decrease the pushing pressure and more effectively create a distinct cephalad advancing force. CONCLUSIONS: Acute cephalad angulation should be considered to increase the margin of safety for epidural approach and catheterization. PMID- 22063378 TI - Anesthesia for surgical correction of coronary artery fistula without extracorporeal circulation: case report. AB - BACKGROUND AND OBJECTIVES: Described by Krause in 1865 (1), coronary artery fistula communicating with cardiac cavities, pulmonary artery, or coronary sinus is very rare. It represents 0.2% to 0.4% of congenital cardiopathies and 0.1% and 0.2% of the adult population undergoing coronary angiography (2). The objective of this report is to present the anesthetic management for surgical closure of a coronary fistula in an elective procedure, considering its particularities. CASE REPORT: This is a 59-year old male patient, whose coronary fistula was diagnosed during clinical investigation of progressive thoracic pain and long-standing dyspnea. The patient underwent surgical correction of coronary artery fistula under general anesthesia without extracorporeal circulation (ECC). The patient evolved without intercurrences, being discharged from the hospital with clinical improvement 7 days after surgery. CONCLUSIONS: Coronary artery fistula is rare, but the anesthesiologist may be faced with this type of patient in distinct situations. Understanding its pathophysiology is important for better perioperative management of the patient, therefore improving the prognosis. PMID- 22063379 TI - Malfunction of the extracorporeal circulation system: case report. AB - BACKGROUND AND OBJECTIVES: The introduction of extracorporeal circulation in clinical practice was decisive for the development of modern cardiovascular surgery. Addition of new procedures and equipment, however, brings inherent risks and complications. The objective of this report is to describe a malfunction of the oxygenation system and emphasize the importance of the interaction among the medical team members to prevent errors and complications. CASE REPORT: During valve replacement and IVC correction surgery, we observed a darker shade of red in the blood on the exit of the oxygenator. Laboratory tests demonstrated severe acidosis and hypoxemia. The entire system was evaluated, but the cause of the malfunction was not found. Measures to reduce damage were successfully instituted. After the surgery, the whole system underwent technical evaluation. CONCLUSIONS: Interaction among the medical team members, early diagnosis, and immediate intervention were fundamental for a favorable outcome. PMID- 22063380 TI - Importance of pre-anesthetic evaluation: case report of a patient with obstructive sleep apnea. AB - BACKGROUND AND OBJECTIVES: The objective of this report was to show the importance of pre-anesthetic assessment in reducing morbidity and mortality of surgical patients and alert to problems and anesthetic care associated with obstructive sleep apnea. CASE REPORT: This is a 28-year old male patient with class II obesity, sleep apnea, hypertension, referred to the pre-anesthetic outpatient clinic for evaluation of uvuloplasty under general anesthesia. After orientation on sleep apnea, explaining to the patient the risks associated with the procedure, and discussing with the surgeon, we decided to review the surgical indication and postpone the procedure. CONCLUSIONS: The pre-anesthetic outpatient clinic is extremely important in reducing morbidity as well as mortality of surgical patients and, especially, in evaluating patients with obstructive sleep apnea, showing to be fundamental for the anesthetic-surgical schedule, orienting conducts to be followed, and interfering positively on patient prognosis. PMID- 22063381 TI - Experimental model of non-controlled hemorrhagic shock in pigs. AB - BACKGROUND AND OBJECTIVES: A better understanding of pathophysiologic changes associated to trauma and hemorrhagic shock can help the development of therapies capable of reducing trauma-related mortality. The objective of this study was to describe a model of non-controlled hemorrhagic shock in pigs. METHODS: Animals received ketamine and midazolam as pre-anesthetic medications. Anesthesia was induced with propofol, and tracheal intubation was performed with the animals on spontaneous ventilation. After intubation neuromuscular blockade was performed. Animals were maintained in controlled mechanical ventilation and normocapnia. Anesthesia was maintained with propofol and fentanyl as needed. Saline was infused during the entire preparation period. MONITORING: Cardioscope, pulse oximeter, invasive blood pressure, volumetric catheter in the pulmonary artery, and urine output by cystostomy were used. Experimental model: after the initial recording of hemodynamic, metabolic, and coagulation variables, right subcostal incision and left lobe liver biopsy were performed. Anesthetic infusion was reduced while the infusion of saline was interrupted. An incision 12cm long 2cm deep was performed in the right liver lobe followed by digital divulsion of the wound. During the hemorrhagic phase, an aspiration probe was placed close to the wound and the volume of aspirated blood was recorded. When mean arterial pressure reached 40mmHg and bleeding was above 700mL the intervention phase was initiated according to the type of study. CONCLUSION: The development of experimental models to reduce high mortality and costs related to trauma is important. PMID- 22063382 TI - Cardiac dysrhythmias and anesthesia. AB - BACKGROUND AND OBJECTIVES: Cardiac dysrhythmias are relatively common in the perioperative period and should be adequately diagnosed and treated by the anesthesiologist whenever indicated. The objective of this article was to review the most relevant aspects of cardiac dysrhythmias, as well as establishing the cause-effect relationship between drugs used in the perioperative period and dysrhythmias. CONTENTS: The mechanisms of dysrhythmias, drugs that can potentially cause dysrhythmias, besides diagnosis and treatment in the perioperative period are presented. CONCLUSIONS: Perioperative dysrhythmias oftentimes do not require treatment and in others the treatment can generate iatrogenicity. Therefore, the knowledge of cardiac dysrhythmias and triggering factors allows a better approach of the perioperative period by the anesthesiologist avoiding wrong or unnecessary treatment. PMID- 22063383 TI - Sex and pain perception and analgesia. AB - Sex is an important factor in painful experience modulation. Large volume of evidence shows that experience is different for males and females, as well as the answer to some classes of analgesics. Laboratory experiments suggest that women have a lower pain threshold than men related to pain from noxious stimuli such as heat, cold, pressure and electrical stimulation. Pain is a dynamic phenomenon under the influence of various mechanisms of excitatory and inhibitory control. The differences in pain perception related to sex may be associated with hyperalgesia in women, but also to the hypoactivity of the inhibitory system of pain in females. The purpose of this review besides showing some relationship for gonadal hormones, central nervous system and pain is to provide reference points for the discussion of one of the most intriguing aspects of the pathophysiology of pain: the differences in the presence of painful stimuli related to gender. PMID- 22063384 TI - Sugammadex((r)): new questions on reversion. PMID- 22063385 TI - Antigenic distance measurements for seasonal influenza vaccine selection. AB - Influenza vaccination is one of the major options to counteract the effects of influenza diseases. Selection of an effective vaccine strain is the key to the success of an effective vaccination program since vaccine protection can only be achieved when the selected influenza vaccine strain matches the antigenic variants causing future outbreaks. Identification of an antigenic variant is the first step to determine whether vaccine strain needs to be updated. Antigenic distance derived from immunological assays, such as hemagglutination inhibition, is commonly used to measure the antigenic closeness between circulating strains and the current influenza vaccine strain. Thus, consensus on an explicit and robust antigenic distance measurement is critical in influenza surveillance. Based on the current seasonal influenza surveillance procedure, we propose and compare three antigenic distance measurements, including Average antigenic distance (A-distance), Mutual antigenic distance (M-distance), and Largest antigenic distance (L-distance). With the assistance of influenza antigenic cartography, our simulation results demonstrated that M-distance is a robust influenza antigenic distance measurement. Experimental results on both simulation and seasonal influenza surveillance data demonstrate that M-distance can be effectively utilized in influenza vaccine strain selection. PMID- 22063386 TI - Antibody persistence and response to 2010-2011 trivalent influenza vaccine one year after a single dose of 2009 AS03-adjuvanted pandemic H1N1 vaccine in children. AB - BACKGROUND: In 2009, several countries used the ASO3-adjuvanted pandemic A/H1N1 vaccine. We assessed the persistence of antibody and the priming induced by a single paediatric dose of this vaccine in children. METHODS: Children aged 15-120 months vaccinated one year before with the ASO3-adjuvanted monovalent pandemic vaccine were tested for the presence of antibody against 2010-2011 TIV components (A/California/7/2009(H1N1), A/Wisconsin/15/2009 (H3N2 A/Perth/16/2009-like) and B/Brisbane/60/2008) before and 21-28 days after each dose of 2010-2011 TIV. Hemagglutination-inhibition (HAI) assay was used. Children received one or two doses of 2010-2011 TIV at 21-28 days interval in relation with their previous immunization status. RESULTS: The results of 128 children were included in the ATP analysis. Before the 2010-2011 TIV administration, 46% of children showed sero-protection to the A/California/7/2009(H1N1) strain (HAI titre >=40) with lower rates of sero-protection to the H3N2A/Perth/16/2009 (37%) and B/Brisbane/60/2008 (19%). After the first dose of 2010-2011 TIV, 98%, 75%, and 57% of vaccinees attained a sero-protective titre to A/California/7/2009(H1N1), A/Perth/16/2009(H3N2), and B/Brisbane/60/2008 strain, respectively. The youngest age group showed significantly lower antibody response to the influenza B component compared to the older age groups after the first dose of vaccine. Among vaccinees who received the second dose of TIV, 96% and 87% had a sero-protective titre to H3N2A/Perth/16/2009 and B/Brisbane/60/2008, respectively. The 2010-2011 TIV was well tolerated. CONCLUSIONS: We found substantial persistence of antibody to the A/California/7/2009 strain one year after a single paediatric dose of AS03 adjuvanted pandemic vaccine and a seroprotective level of antibody to this strain in virtually all children who received one year later a single dose of the 2010 2011 TIV. In contrast, two doses of the 2010-2011 TIV were necessary to induce an adequate immune response to the A/Perth/16/2009(H3N2) and B/Brisbane/60/2008 strains in children previously naive to seasonal vaccine. PMID- 22063387 TI - Parental perception of influenza in Italy: a web survey. PMID- 22063388 TI - Lessons from an online debate about measles-mumps-rubella (MMR) immunization. AB - OBJECTIVE: To provide strategies for immunization advocates on how best to participate in online discussion forums about immunization. METHODS: Content and thematic analysis of an online discussion forum held following the national screening of a documentary about the measles-mumps-rubella (MMR) vaccine and autism scare. A subsample of branches containing more than 20 posts was analysed. Each distinct message (a "post") was coded for the author's manifest position on immunization, author type, topic, and evidence presented or sought. RESULTS: From 103 distinct branches there were 1193 posts sent over a 31/2 h period. We selected the 13 longest branches containing 466 posts from 166 individuals. One third of these individuals were explicitly critical of MMR immunization and one third sought information. The remainder were ambivalent but seeking no information (5%), supportive (14%), or unstated (15%). Among five author categories, only 4% identified themselves as health professionals. Topics included alleged adverse effects of immunization (35%); autism spectrum disorders treatment and causes (31%); vaccine ingredients (12%); a conspiracy (9%); immunization policies (8%); and measles, mumps or rubella (4%). Scientific concepts of evidence failed to compete with lay concepts and personal anecdotes prevailed. CONCLUSIONS: Health professionals and other advocates of immunization should engage in similar types of post-broadcast online discussion forums in a planned and strategic manner that accounts for the decision processes of lay people. This involves expanding and diversifying the support base of people contributing to the forum; setting the agenda; introducing messages known to influence behaviour; not overselling vaccination; and avoiding personal attacks. PMID- 22063389 TI - Effect of modified-live porcine reproductive and respiratory syndrome virus (PRRSv) vaccine on the shedding of wild-type virus from an infected population of growing pigs. AB - There are ongoing efforts to eliminate porcine reproductive and respiratory syndrome virus (PRRSv) from regions in the United States swine industry. However, an important challenge for the accomplishment of those efforts is the re infection of pig units due to the area spread of PRRSv. The objective of this study was to evaluate the effect of PRRS modified-live virus vaccine (MLV) on viral shedding and on dynamics of PRRSv infection in pig populations raised under commercial conditions. The study composed of two rooms of 1000 pigs each. Ten percent of pigs of each room were inoculated with a field isolate of PRRSv. Rooms had separate air spaces and strict scientifically validated biosecurity protocols were adopted to avoid movement of pathogens between rooms. At 8 and 36 dpi (days post inoculation), all pigs of the challenge-vaccine group were inoculated with a MLV vaccine. Pigs of the challenge-control group were placebo-inoculated. Blood and oral fluid samples were collected from each room at 0, 8, 36, 70, 96 and 118 dpi for PRRSv RNA detection using PCR. PRRSv-antibodies were also screened from blood serum samples with a commercially available ELISA test. Additionally, tonsil scraping samples were collected from both groups at 70, 96 and 118 dpi. Moreover, air samples were collected 6 times per week from 0 to 118 dpi and were tested for PRRSv RNA using qPCR assay. There was no difference in the PRRSv infection dynamics measured as duration and magnitude of viremia and seroconversion. Also, there was no difference in the frequency of tonsil scraping samples PRRSv-positive by PCR. However, the challenge-vaccine group had significantly less PRRSv shed compared to the challenge-control group. The challenge-vaccine group had significant less PRRSv-positive oral fluids at 36 dpi. Moreover, the challenge-vaccine group had significant reduction in the cumulative PRRSv shed in the air. PMID- 22063390 TI - Progress in newborn hepatitis B vaccination by birth year cohorts-1998-2007, USA. AB - BACKGROUND: In 1999, the American Academy of Pediatrics (AAP) and the U.S. Public Health Service (USPHS) issued a joint statement on thimerosal in vaccines, which advised clinicians to temporarily postpone the first dose of hepatitis B vaccine for infants born to hepatitis B surface antigen (HBsAg)-negative women. In 2005, the Advisory Committee on Immunization Practices (ACIP) updated the strategy to improve prevention of perinatal and early childhood hepatitis B virus (HBV) transmission. OBJECTIVES: To evaluate the progress in hepatitis B birth dose vaccination coverage in birth year cohort from 1998 to 2007 and assess the impact of changes in ACIP recommendations on the birth dose coverage. METHODS: Birth year cohort study of hepatitis B birth dose vaccination status of 200,865 children aged 19-35 months in the United States and by selected socio-demographic factors; percentage increases of hepatitis B birth dose vaccination coverage between two consecutive birth year cohorts from 1998 to 2007. RESULTS: From 1998 to 1999, hepatitis B birth dose vaccination coverage declined overall in the United States and among selected socio-demographic groups (P<0.001). Conversely, from 1999 to 2007 hepatitis B birth dose vaccination coverage increased significantly by birth year cohort (P<0.001), from approximately 30% in the 1999 birth year cohort to approximately 60% in the 2007 birth year cohort. The first significant increase in hepatitis B birth dose vaccination coverage occurred from 2000 to 2001 birth year cohort. Coverage increases ranged from 8.4% to 11.9% (P<0.001) in the U.S. and across all socio-demographic strata. The second largest increase in hepatitis B birth dose vaccination coverage occurred from 2005 to 2006 birth year cohort in the U.S. and among almost all socio-demographic strata, ranging from 5.6% to 8.7% (P<0.001). Forty-one of the 50 states and the District of Columbia (80%) in the U.S. had increases in hepatitis B birth dose vaccination coverage from 2005 to 2006 birth year cohort. CONCLUSIONS: The United States has made substantial progress in increasing hepatitis B birth dose vaccination and recovered from coverage declines associated with temporary postponement of the birth dose in 1999. The hepatitis B birth dose coverage in the U.S. remains substantially below the Healthy People 2020 target of 85%. PMID- 22063391 TI - Relationships between sensory and objective measures of meat tenderness of beef m. longissimus thoracis from bulls and steers. AB - This study assessed whether relationships between sensory and objective measures of beef tenderness were different for beef from bulls and steers. Trained panelists and instruments were used to measure tenderness of m. longissimus thoracis from bulls (n=58) and steers (n=59). Four measures of sensory tenderness (hardness, cohesiveness, toughness and chewiness) were closely correlated with each other, and moderately correlated with mechanical measures using a Warner Bratzler device, a MIRINZ tenderometer and a compression cell in an Instron device. With increasing values of objective measures, sensory scores increased at a decreasing rate. Use of a general-least-squares model with sensory measures as the dependent variable and objective measures as covariates (linear and quadratic), showed that, after adjustment to a constant objective measure, significant differences between bulls and steers in sensory measures of toughness remained (P<0.001). Adjusted sensory measures also decreased with increasing ultimate pH in some instances. The bull/steer effects on adjusted sensory measures were smaller when regressions were fitted within the two groups. It is concluded that when using a common prediction equation to estimate sensory scores from objective measures, it can be expected that groups or individual samples with higher scores will tend to be under-estimated, and those with lower scores, over-estimated. PMID- 22063392 TI - Effect of organic production system on broiler carcass and meat quality. AB - The effect of organic production on broiler carcass and meat quality was assessed. Two hundred and fifty Ross male chickens were assigned to two different systems of production: conventional, housing in an indoor pen (0.12 m(2)/bird); organic, housing in an indoor pen (0.12 m(2)/bird) with access to a grass paddock (4 m(2)/bird). At 56 and 81 days of age, 20 chickens per group were slaughtered to evaluate carcass traits and the characteristics of breast and drumstick muscles (m. pectoralis major and m. peroneus longus). The organic chickens had carcasses with a higher breast and drumstick percentages and lower levels of abdominal fat. The muscles had lower pHu and water holding capacity. Instead cooking loss, lightness values, shear values, Fe, polyunsaturated fatty acids of n-3 series and TBA-RS were higher. The sensory quality of the breast muscle was better. Organic production system seems to be a good alternative method, due to better welfare conditions and good quality of the carcass and meat. A negative aspect was the higher level of TBA-RS in the muscles, probably due to greater physical activity. PMID- 22063393 TI - Utilization of cereal and fruit fibres in low fat dry fermented sausages. AB - The effect of addition of cereal and fruit dietary fibres on the sensory properties of reduced-fat, dry fermented sausages was studied. Dry fermented sausages with 6 and 10% pork backfat were manufactured, with addition of cereal (wheat and oat) and fruit (peach, apple and orange) dietary fibres, at 1.5 and 3% concentrations. The energy value reduction of the final products was close to 35% and their final fibre contents, after ripening, were 2 and 4%, respectively. The ripening process was monitored by physico-chemical and microbiological analysis. Sensory properties were analyzed using triangular and hedonic tests and, a texture profile analysis was carried out. A correlation principal component analysis was performed. The results showed that the sensory and textural properties of batches with 3% dietary fibre were the worst, due to their hardness and cohesiveness. The best results were obtained with sausages containing 10% pork backfat and 1.5% fruit fibre especially those with orange fibre, which gave organoleptic characteristics similar to conventional high fat products. Thus, reduced fat sausages fortified with dietary fibre can be obtained with an acceptable sensory profile. PMID- 22063394 TI - Meat tenderization by calcium chloride after osmotic dehydration. AB - In this study, meat was tenderized by dipping the meat in a calcium-containing solution after osmotic dehydration. Dehydrated meats were dipped in a 150 mM calcium chloride solution for 3 h, and after that stored for 24, 48, and 168 h at 3 ~ 4 degrees C. Then, meat was subjected to texture measurement, sensory evaluations, biochemical analysis and histological observations. A gradual decrease in the firmness and higher tenderness sensory scores were observed in the meat treated with calcium chloride as compared with the untreated meat. Few differences were observed in water holding capacity by treatment at any stage of storage. A gradual increase in the myofibril fragmentation from the calcium chloride-treated meats was observed throughout the storage compared with the controls. Broadening of the I band and a disordered Z-line were observed in the treated meat. The deformation of the honeycomb-like structure of the endomysium was also observed in the treated samples. Therefore, the dipping in 150 mM calcium chloride solution after dehydration can be applied to improve meat tenderness without detrimental effects on other palatability and quality traits. PMID- 22063395 TI - The effects of acetic acid, gluconic acid and trisodium citrate treatment of beef trimmings on microbial, color and odor characteristics of ground beef through simulated retail display. AB - Antimicrobial effects of selected acidulants in a ground beef production system were studied. Lean beef trimmings were inoculated with Escherichia coli (EC) and Salmonella Typhimurium (ST) then treated with either 5% acetic acid, 5% gluconic acid (GA) or 5% trisodium citrate and then compared with an untreated control (C). Trimmings were ground, packaged and sampled at 0, 1, 2, 3 and 7 days of display for EC, ST, coliforms, aerobic plate counts (APC), sensory color and odor as well as instrumental color traits. Acetic acid reduced (P<0.05) all bacterial types evaluated, but caused changes (P<0.05) in ground beef color (L*, a* and b* values) and odor characteristics. Conversely, although GA reduced (P<0.05) EC and APC, it had little effect on color or odor characteristics as compared with C. Trisodium citrate did not affect (P>0.05) microbial populations, color or odor characteristics of ground beef. PMID- 22063396 TI - Sensory colour assessment of fresh meat from pigs supplemented with iron and vitamin E. AB - Pork muscle samples (M. longissimus dorsi) were obtained from pigs given one of four dietary treatments: (1) control diet; (2) supplemental iron [7-g iron (II) sulphate/kg feed]; (3) supplemental vitamin E (200-mg dl-alpha-tocopheryl acetate/kg of feed); and (4) supplemental vitamin E+supplemental iron. Muscle cores were packaged in polythene bags and placed in a retail refrigerated display cabinet at 5+/-1 degrees C, under fluorescent light (1000 LUX) for up to 5 days. Samples were subjected to visual colour evaluation by a trained sensory panel (n=12) at 0, 1, 3 and 5 days. In addition instrumental L*, a* and b* values and drip loss were measured on each day of analysis. All samples became less red and browner over storage time in the refrigerated display cabinet. The vitamin E treated samples were more red and less brown compared with the other samples on successive days in the cabinet followed by the control, iron/vitamin E and iron treatments. The iron/vitamin E treatment was positioned midway between the vitamin E and iron treatments indicating that the vitamin E in the samples was effective in reducing the pro-oxidative effect of iron in inducing the brown metmyoglobin pigment development. Iron supplementation did not significantly (P<0.05) increase M. longissimus dorsi iron tissue levels, but had a detrimental effect on the visual sensory properties of the iron and iron/vitamin E treatment groups with greater metmyoglobin formation. Vitamin E appears to have promoted non-supplemental iron absorption in the vitamin E treated group without the detrimental sensory colour characteristics associated with ferrous sulphate supplementation. Drip loss increased in all samples during the course of the experiment with no significant (P<0.05) differences between the experimental groups. The panellists were able to differentiate the four experimental groups on each day of the study and were more effective in evaluating the colour quality of samples than instrumental assessment, i.e. the Hunter L* a* b* method. PMID- 22063397 TI - Purification of transglutaminase and its effects on myosin heavy chain and actin of spent hens. AB - The purpose of this study was to purify pig plasma transglutaminase (TGase) and examine its effects on the myosin heavy chain and actin of the breast muscles from spent hens at different temperatures. TGase (0.3 units/mg) was added to myofibrillar proteins solution (0.5 ml) at 4 degrees C for 0, 4, 8, 12, 24 and 48 h; at 25 degrees C for 0, 1, 2, 4, 8, 12, 24 and 48 h; at 37 degrees C for 0, 5, 10, 30 and 60 min. The results of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that plasma TGase was composed of units of molecular weights approximately 75,000 and 80,000. TGase added to the myofibrillar proteins solution indicated that the concentration of the myosin heavy chain and actin decreased when incubated at 4 degrees C for 48 h and when incubated at 25 degrees C for 2 h. Moreover, the relative intensity determined by scanning densitometry of the SDS-PAGE gel indicated that the myosin heavy chain and actin concentration decreased to 45 and 64%, respectively. In addition, the relative intensity of the myosin heavy chain and actin declined to 7 and 63%, respectively, when incubated at 37 degrees C for 5 min. The relative intensity of both the myosin heavy chain and actin decreased with time when incubated at 25 and 37 degrees C. PMID- 22063398 TI - The effect of injection level and cooling method on the quality of cooked ham joints. AB - The effect of cooling method and injection level on cooling rate, weight loss and quality of large cooked ham joints was investigated. Two cooling methods, vacuum (VC) and conventional (CC) and two injection levels (20 and 30%) were examined. VC reduced the cooling rate (70 degrees C to 4 degrees C) significantly in comparison to the CC (2.5 h vs. 12.5 h). Under these test conditions, VC conformed to recent safety guidelines for cooked meat joints of a reduction in temperature to 5 degrees C inside 10 h in comparison to CC. The injection rate had no affect on the cooling rate. Increased weight loss due to vacuum cooling was off-set by increasing the level of brine injection in pork legs from 20 to 30% and getting a yield after VC similar to that for CC hams injected at 20%. Injection rate had no affect on the sensory attributes but cooling method did; VC hams were slightly tougher (P<0.05) and drier (P<0.01) than CC hams. While VC hams injected to a 30% rate were less tender and juicy than CC hams injected at a 20% rate, as indicated by sensory scores and some instrumental texture parameters, they were similar in shear value and in overall acceptability. PMID- 22063399 TI - Continuous distribution analysis of T(2) relaxation in meat-an approach in the determination of water-holding capacity. AB - Continuous distribution analysis as well as traditional bi-exponential fitting analysis were carried out on NMR T(2) relaxation data measured 24 h post-mortem in 74 pork meat samples from M. longissimus dorsi. Areas of relaxation populations found by continuous distribution analysis and corresponding time constants were determined. Comparison of correlations to water holding capacity (WHC), determined by Honikel's bag method [Honikel, K. O. (1998). Reference methods for the assessment of physical characteristics of meat. Meat Science, 49, 447-457], revealed superior performance of continuous distribution analysis (r= 0.85) compared with traditional bi-exponential fitting analysis (r=-0.77). Furthermore, the changes in continuous relaxation time distribution spectra were followed during loss of water from meat samples by centrifugation. It was found that the area of the slowest relaxation population (T(22)) decreased proportionally with the amount of expelled water. A physical explanation for the obtained correlation between continuous relaxation time distribution data and WHC is given upon the results from these data. PMID- 22063400 TI - Temperature and catecholamine effects on metabolism of perfused isolated rabbit muscle. AB - Biceps brachii muscle was isolated from anaesthetized New Zealand rabbits and perfused for 30 min with bovine red cells, while electrically stimulated at 0.1 Hz, 50 V. Temperature was maintained at 34 (physiological temperature of this muscle), 36 or 38 degrees C in the first experiment (Exp 1). In the second experiment (Exp 2), temperature was maintained at either 34 or 38 degrees C and the muscle was perfused with 2 ng/ml adrenaline and 10 ng/ml noradrenaline for 5 min during the perfusion. Whatever the temperature, twitch force decreased (P<0.01) during perfusion indicating muscular fatigue. Total turnover rate of "energy-rich" phosphate was higher at 38 degrees C than at 34 degrees C (P<0.05) during the first 30 min after the perfusion was stopped in Exp 1 and tended to be higher between 30 and 60 min (P<0.10) in Exp 2. Catecholamine perfusion had no effect on contraction and on muscle metabolism whatever the temperature. Our results show that an increase in temperature of 4 degrees C above the physiological temperature decreases the resistance of oxygenated rabbit muscle to fatigue. In anoxic muscle, temperature increase accelerates the turnover of "energy-rich" phosphate compounds, which is known to be detrimental to meat quality. PMID- 22063401 TI - The effect of nitrite and starter culture on microbiological quality of "chorizo" a Spanish dry cured sausage. AB - The effect of nitrite and starter culture on the survival of Enterobacteriaceae, Micrococcaceae, Lactic acid bacteria and other microorganisms was evaluated during ripening of "chorizo", a Spanish dry sausage. Sodium nitrite 50 and 150 ppm and Lactobacillus sake CL35 added to the "chorizo" have a significant inhibitory effect on Enterobacteriaceae counts but did not on Micrococcaceae. The use of Lact. sake could be an adequate safety factor in this product. PMID- 22063402 TI - Microbial, instrumental color and sensory color and odor characteristics of ground beef produced from beef trimmings treated with ozone or chlorine dioxide. AB - The effects of beef trimming decontamination with ozone and chlorine dioxide on ground beef microbial, color and odor characteristics were studied. Beef trimmings were inoculated with Escherichia coli (EC) and Salmonella Typhimurium (ST), then treated with either 1% ozonated water for 7 min (7O) or 15 min (15O), or with 200 ppm chlorine dioxide (CLO) and compared with a control (C). Trimmings were ground, packaged and sampled at 0, 1, 2, 3 and 7 days of display for EC, ST, coliforms (CO), aerobic plate counts (APC), instrumental color, as well as sensory color and odor characteristics. The 15O and CLO treatments reduced (P<0.05) all bacterial types evaluated, whereas the 7O treatment reduced (P<0.05) APC and ST. All treatments caused ground beef to become lighter (L*) in color (P<0.05); however, the 15O treatment was similar (P>0.05) in redness (a*), percentage discoloration, beef odor and off odor intensities when compared to C. PMID- 22063403 TI - Effect of artificial rearing on lamb welfare and meat quality. AB - Twenty male Comisana lambs were equally divided into two groups. Ten subjects were artificially reared, 10 others were ewe reared and used as control. Unseparated control animals displayed increased cellular immune response to a percutaneous injection of phytohemagglutinin (P<0.001). During the open field test, ewe-reared lambs showed a higher number of flight attempts (P<0.01). Carcass yield were higher for artificially reared animals (P<0.05). Conversely, legs of ewe-reared animals had significantly more fat (P<0.05) and a higher content of saturated fatty acids (P<0.001). Polyunsaturated fatty acid content was higher in artificially reared lamb meat (P<0.01), although the ratio n-6/n-3 was well above the recommended values. The triangle test showed a significant difference in sensory analysis between the two products (P<0.05). Finally, for both rearing systems legs without subcutaneous fat showed a higher percentage of polyunsaturated fatty acids and a corresponding lower content of saturated fatty acids (P<0.001). PMID- 22063405 TI - Lipid oxidation in n-3 fatty acid enriched Dutch style fermented sausages. AB - Dutch style fermented sausages were manufactured with a substitution of 10%, 15% and 20% of pork backfat by flaxseed oil and canola oil, pre-emulsified with soy protein isolate. The 15% and 20% substitution were also reached by adding encapsulated flaxseed oil and encapsulated fish oil and by adding flaxseed oil, pre-emulsified with sodium caseinate, respectively. The products were sliced, packaged in an oxygen-enriched atmosphere and stored in the dark for 12 weeks at 7 degrees C. No differences were detected in moisture, protein and fat content between control and modified sausages, with the exception of the formulation with sodium caseinate. The PUFA/SFA ratio increased from 0.30 in the control to 0.42 0.48 in the sausages with canola oil and to 0.49-0.71 in the sausages with flaxseed oil. The n-6/n-3 ratio decreased from 11.20 in the control to 6.94-5.12 in the sausages with canola oil and to 1.93-1.05 in the sausages with flaxseed oil. The addition of canola oil and encapsulated flaxseed oil resulted in a comparable shelf life as the control in terms of lipid oxidation. In the samples with addition of pre-emulsified flaxseed oil, especially with sodium caseinate, lipid oxidation clearly increased during storage. Physical and sensory analysis showed that the sausages with encapsulated fish oil and flaxseed oil resembled the control most. PMID- 22063406 TI - High pressure applied to frozen ham at different process stages. 1. Effect on the final physicochemical parameters and on the antioxidant and proteolytic enzyme activities of dry-cured ham. AB - This paper describes the effect of high pressure (400MPa and 600MPa) applied to frozen hams at early stages of the dry-cured ham process: green hams (GH) and hams at the end of the resting stage (ERS), on some physicochemical parameters and on antioxidant and proteolytic enzyme activities in the final product. No significant differences were observed among treatments either in the drying kinetics or in the physicochemical characteristics. However, when high-pressure was applied to frozen GH hams it produced a superficial denaturation that affected salt absorption and, consequently, the proteolysis index. The high pressure treatment applied during the processing of previously frozen GH and ERS hams reduced the antioxidant enzyme activities slightly (superoxide dismutase, catalase and glutathione peroxidase) but did not affect the cathepsin B and the cathepsin B+L activities. PMID- 22063407 TI - High pressure applied to frozen ham at different process stages. 2. Effect on the sensory attributes and on the colour characteristics of dry-cured ham. AB - This paper describes the effect of high pressure (400MPa and 600MPa) applied to frozen hams at early stages of the dry-cured ham process: green hams (GH) and hams at the end of the resting stage (ERS), on the appearance, some texture and flavour parameters and on the instrumental colour characteristics of dry-cured hams. Pressurized hams showed slightly lower visual colour intensity than the control ones. In general, pressurization did not have a significant effect on the flavour characteristics of the final product. The 600-MPa hams from the ERS process showed significantly lower crumbliness and higher fibrousness scores than the control and the 400-MPa hams. However, none of these differences were enough to affect the overall sensory quality of the hams negatively. Regarding instrumental colour characteristics (L(*)a(*)b(*)), an increase in lightness was observed in the biceps femoris muscle from GH hams pressurized at 400MPa and 600MPa but not in the ERS hams. PMID- 22063408 TI - On-line measurements in pig carcass classification: Repeatability and variation caused by the operator and the copy of instrument. AB - For nearly all pigs slaughtered in the EU, the lean meat content is assessed on line at the slaughter line. The assessment is made indirectly by an instrument performing a number of informative measurements including the thickness of back fat as one of the most important and common measurements. Several types of instruments are used for making the measurements. The quality of the calibration (the prediction ability) has to be approved by the EU Commission. However, the maintenance of instruments, training of operators, working conditions and other factors influencing the routine are quite as important for the accuracy as the calibration. As a part of an EU funded project, partners representing thirteen European countries have investigated the instruments used in their countries focusing on the precision of indirect measurements. The preconditions have differed considerably between the countries resulting in a wide range of estimates of the repeatability and the reproducibility (precision) of fat and muscle thickness. Totally, there have been three different types of manual instruments - invasive probe instruments from three manufacturers, non-invasive ultrasound and callipers. Furthermore, the precision of two automatic instruments with respect to lean meat content has partly been estimated. Even though neither the aim nor the design of the experiments was set for a direct comparison between different instruments, none of them seemed to deviate notably from the others with respect to the precision of fat thickness. In this study, the only investigated influencing factors were the variations in operators and copies of instruments. Generally, the variations between operators were more important than the variation between copies of the same type of instrument. PMID- 22063409 TI - Comparison of ascorbic acid and sodium erythorbate: Effects on the 24h display colour of beef lumbar vertebrae and longissimus lumborum packaged in high-oxygen modified atmospheres. AB - Sodium erythorbate and ascorbic acid were compared as a means to stabilize surface colour of bone-in beef steaks in high-oxygen modified atmosphere (80% oxygen and 20% carbon dioxide). Bone-in strip loins (n=8) were fabricated into 1.9-cm thick steaks, of which both the lumbar vertebrae and longissimus lumborum were topically treated with either ascorbic acid or sodium erythorbate (0, 0.05, 0.1, 0.5, 1.0, or 1.5%, wt/wt basis). Colour (L(*)a(*)b(*)) was evaluated before treatment and 24h after packaging (display at 1 degrees C). Sodium erythorbate was as effective as ascorbic acid for inhibiting vertebrae discolouration (P>0.05). Either reducing agent at 0.5, 1.0, or 1.5% improved (P<0.05) vertebrae redness (compared with 0%, 0.05% and 0.1%). No detrimental effects on muscle colour were observed. When selecting antioxidants intended for bone-in beef steaks displayed in high-oxygen packaging, sodium erythorbate may be a cost effective substitute for ascorbic acid. PMID- 22063410 TI - Effect of slaughter season on fatty acid composition, conjugated linoleic acid isomers and nutritional value of intramuscular fat in Barrosa-PDO veal. AB - This paper describes the influence of slaughter season on lipid content, fatty acid composition, conjugated linoleic acid (CLA) isomeric profile and nutritional value of fat in Barrosa veal from calves reared according to the specifications of the Protected Designation of Origin (PDO). Barrosa purebred calves (n=27) were raised in a traditional production system and slaughtered in early autumn (October) and late spring (June). Barrosa-PDO veal only presented seasonal differences in the levels of some minor fatty acids and CLA isomers, as well as in the PUFA/SFA ratio. Based on the analysed grass intake indicators, it was shown that veal-PDO has similar values to pasture-fed cattle for both slaughter seasons. From a human nutrition perspective, intramuscular fat in Barrosa-PDO veal has a high nutritional value throughout the year, since CLA contents and the percentages of the c9,t11 isomer are relatively high, and the n-6/n-3 ratios are within the recommended values for the human diet. PMID- 22063411 TI - Post-mortem metmyoglobin reduction in fresh venison. AB - The accumulation of metmyoglobin (MetMb) at the surface of meat during storage contributes significantly to its discolouration. Under appropriate conditions it may be possible to utilise residual meat MetMb reducing activity to maintain fresh colour. Venison meat colour stability is poorer compared with other species. Hence, we evaluated the capacity of completely discoloured venison (n=12 animals) to reduce MetMb under anaerobic conditions in order to decipher more clearly the role MetMb reducing activity may play. The reducing capacity of venison (1 day, 3, and 6 weeks post-mortem), electrical stimulation, surface location (top and bottom) and rigor temperature (15 and 35 degrees C) on MetMb were evaluated. Surface MetMb decreased (P<0.001) during storage while deoxymyoglobin increased (P<0.001) demonstrating MetMb reduction. Metmyoglobin reduction was greater (P<0.001) in venison which entered rigor at 15 degrees C, the reduction at the bottom surface of the steaks was greater (P<0.001) compared with the top surface, and electrical stimulation had no affect (P>0.05). These data demonstrate that metmyoglobin reducing activity occurs anaerobically in completely discoloured venison following storage display. The practical application for this finding needs to be determined. PMID- 22063412 TI - Effects of oleoresin-tocopherol combinations on lipid oxidation, off-odor, and color of irradiated raw and cooked pork patties. AB - Lipid oxidation, color, and volatiles of double-packaged pork loins with various oleoresin or oleoresin-tocopherol combinations were determined to establish the best oleoresin-tocopherol conditions that can improve the quality of irradiated raw and cooked pork loins. Rosemary and alpha-tocopherol combination at 0.05% and 0.02% of meat weight, respectively, showed the most potent antioxidant effects in reducing both TBARS values and the amounts of volatile aldehydes in irradiated raw and cooked pork loins. The antioxidant combination, however, did not affect the production of sulfur volatiles responsible for irradiation off-odor and showed little effects on color changes in irradiated raw and cooked pork loins. Exposing double-packaged irradiated pork to aerobic conditions for 3days during the 10-day storage was effective in controlling both lipid oxidation and irradiation off-odor, regardless of packaging sequences. PMID- 22063413 TI - Lipid oxidation and color change of salted pork patties. AB - The purposes of this study were to explore the interaction of lipid oxidation and pigment oxidation in salted pork patties and to study the mutual relationship between lipid and pigment oxidation caused by replacing sodium chloride with potassium chloride at low salt levels. For fresh pork patties, a(*) and b(*) values decreased with the replacement of sodium chloride by potassium chloride. However, there were no significant differences of L(*) values, pH values, total pigments and heme irons by replacement of NaCl with KCl; however, the replacement reduced 2-thiobarbituric acid reactive substances (TBARS). The addition of sodium tripolyphosphate, ascorbic acid and carnosine did not change a(*) and b(*) values of raw pork patties. However, raw pork patties with 0.25% sodium tripolyphosphate had significantly higher L(*) value compared to other samples. The pH of raw pork patties with 0.5% carnosine was higher than those of other treatments. The pH of raw pork patties with 0.25% sodium tripolyphosphate was significantly higher than that of the control treatment with no antioxidant. Samples with 550ppm ascorbic acid had significantly higher total pigment and heme iron than patties with 0.25% sodium tripolyphosphate. Although control treatment with no antioxidant had slightly higher TBARS values, these differences were not large enough to be significant. PMID- 22063414 TI - Characterizing beef muscles with optical scattering and absorption coefficients in VIS-NIR region. AB - We developed a fiber optical probe to measure spatially resolved diffuse reflectance from beef samples in VIS-NIR bandwidth of 450-950nm. The optical scattering and absorption coefficients were obtained by fitting the measurements with diffuse equation. Beef absorption coefficients are related to the sample chemical compositions such as the concentration of myoglobin and its derivatives; while scattering coefficients depend on meat structural properties such as sarcomere length and collagen concentration. Structural properties are also key factors in determining beef tenderness, therefore we hypothesize that a correlation exists between optical scattering and cooked Warner-Bratzler shear (WBS) force. Thirty-two, unfrozen beef muscle samples obtained from different animals were used in the correlation study. We found a higher scattering coefficient was associated with a higher cooked WBS. A linear regression analysis showed that sample scattering coefficients were significantly (p<0.0001) correlated to the corresponding WBS with a coefficient of determination (R(2)) of 0.59. PMID- 22063415 TI - Injection of conjugated linoleic acid into beef strip loins. AB - Beef strip loins (IMPS 180; n=15) were sectioned in thirds and sections (n=45) were left untreated (CNT) or injected with either a commercial powder conjugated linoleic acid (CLA) source (Powder) or a commercial oil CLA source (Oil), whose major isomers were 18:2cis-9, trans-11 and 18:2trans-10, cis-12 CLA isomers. Fresh Oil steaks had 3.20 and 3.15, Powder steaks had 4.67 and 4.62, and CNT steaks had 0.19 and 0.02mg/g muscle tissue (wet basis) of the cis-9, trans-11 and trans-10, cis-12 CLA isomers, respectively. TBARS were similar (Oil) and lower (Powder), compared to CNT. Powder steaks had similar instrumental color, and beef and off flavor characteristics as CNT. Artificial marbling was created with Oil steaks having USDA Small(79) and Powder steaks having USDA Modest(86) marbling scores, while CNT steaks had USDA Slight(94) marbling scores. Injection of CLA can be effective in significantly increasing CLA and potentially creating artificial marbling. PMID- 22063416 TI - The relationship between different pork carcass lean yield definitions and the market carcass value. AB - Cutout and dissection data from 265 carcasses were used to study the impact of the lean yield definition on their ability to discriminate lean carcasses from fat carcasses. The same data were used to evaluate the relationship between the various definitions of lean yield, such as the lean yield predicted by the Destron optical probe (LYDESTRON), the saleable meat yield (SMY), the Canadian lean yield (LY2000) and the lean meat percentage (TVM), and the market carcass value. Based on the highest number of carcasses assigned to the extreme grades (leaner and fatter), the TVM had the greatest discriminating capability based on carcass leanness. The correlation coefficients obtained between market carcass value and LYDESTRON, SMY, LY2000 and TVM were 0.14, 0.54, 0.36 and 0.23, respectively. These weak correlations demonstrate that lean yield alone does not adequately explain the variation in market value between carcasses. Lean yield therefore cannot be used to estimate market value independently of the definition used. PMID- 22063417 TI - Effects of dietary daidzein supplementation of pregnant sows on carcass and meat quality and skeletal muscle cellularity of the progeny. AB - The effects of dietary daidzein during late gestation on maternal performance, neonatal body composition, carcass and meat quality at market weight, and skeletal muscle cellularity were studied. Multiparous sows received a soybean free diet (n=8, control) or the same diet supplemented with 1mg daidzein/kg body weight (n=7) daily from d 85 of gestation to parturition. Litter size, litter weight, and birth weight remained unaffected by daidzein feeding. In newborn piglets from litters >15, the proportions of muscle tissue and skin tended to be decreased (P=0.09) or increased (P=0.03), respectively, after gestational daidzein feeding. The body fat percentage was higher in response to maternal daidzein (P=0.04). Postnatal growth and carcass composition at 180d of age were not affected, however, maternal daidzein supplementation led to increases in longissimus muscle pH(45) (P=0.02) and pH(end) (P=0.11) in pigs from large litters. The proportion of fast-twitch glycolytic fibres in semitendinosus muscle was increased (P=0.06) by maternal daidzein feeding. The results suggest that supplemental daidzein in the maternal diet during late gestation marginally affects meat quality and skeletal muscle cellularity of the progeny. PMID- 22063418 TI - Post-mortem activity of the glycogen debranching enzyme and change in the glycogen pools in porcine M. longissimus dorsi from carriers and non-carriers of the RN(-) gene. AB - Glycogen debranching enzyme (GDE) is together with glycogen phosphorylase responsible for the degradation of glycogen. The present study compares the post mortem activity of GDE and breakdown of the glycogen pools in M. longissimus dorsi of RN(-) carrier pigs and in wild type animals. The activity of GDE (n=14) and pH (n=20) was measured 0.5, 3, 5, 24 and 48h post-mortem. The change in pro glycogen and in macro-glycogen content (n=20) was followed until 216h post-mortem and the transcription level of GDE, glycogenin and glycogen synthase m-RNA (n=19) were measured 0.5h post-mortem. Both the activity of GDE and the transcription level of GDE were found to be similar in RN(-) carriers and wild type animals shortly after slaughter. However, the activity declined faster in wild type animals compared with RN(-) carriers with increasing time post-mortem. The contents of both pro-glycogen and macro-glycogen were higher in RN(-) carriers compared with wild type animals, and further, the proportion of macro-glycogen was higher in RN(-) carriers compared with wild type animals. During the post mortem period, only degradation of pro-glycogen was observed in both genotypes. The decrease in pH was faster and the ultimate pH lower in RN(-) carriers than in wild type animals. It was suggested that the higher GDE activity in the late phase of the post-mortem period in muscles from RN(-) carriers renders the extended pH decrease in these muscles. PMID- 22063419 TI - Species-specific PCR for the identification of ruminant species in feedstuffs. AB - A polymerase chain reaction (PCR) method based on the nucleotide sequence variation in the 12S ribosomal RNA mitochondrial gene has been developed for the specific identification of bovine, ovine and caprine DNAs in feedstuffs. The primers designed generated specific fragments of 84, 121 and 122pb length for bovine, ovine and caprine species, respectively. The specificity of the primers designed was tested against 30 animal species including mammals, birds and fish, as well as eight plant species. Analysis of experimental feedstuffs demonstrated that 0.1% of raw and heated bovine, ovine or caprine tissues can be easily detected using the species-specific primers developed. The performance of this method is not affected by prolonged heat treatment, and consequently it could be very useful to verify the origin of the raw materials in products submitted to denaturing technologies, for which other methods cannot be applied. PMID- 22063420 TI - Development in myofibrillar water distribution of two pork qualities during 10 month freezer storage. AB - The effects of fresh meat quality (PSE versus DFD), freezing temperature (-20 degrees C versus -80C degrees ) and duration of freezer storage on changes in water mobility and distribution were followed at intervals of 1-2 months during 10-month freezer storage of pork using low-field NMR T(2) relaxometry. Fresh meat quality was found to have a strong significant effect (P<0.0001) on the amount of loosely bound water (relaxation time >100ms) also after freezing, which was reflected in a significantly lower cooking yield in PSE meat compared with DFD meat (P<0.0001). While no significant changes in the cooking yield were observed with increasing length of freezer storage, NMR T(2) relaxation measurements revealed a significant increase in the amount of loosely bound water in PSE meat with increasing length of freezer storage. This finding indicates that NMR T(2) relaxation measurements are quite sensitive to freezing-induced changes in the meat structure, causing a shift in the distribution of water and possibly capable of detecting these before they are reflected in a reduced cooking yield. In addition, an interaction between fresh meat quality and effect of length of freezer storage on the amount of very mobile water easily lost as drip was observed, implying that PSE meat is more susceptible to freezer storage-induced deteriorative changes in the meat structure, causing a shift in the distribution of water, than DFD meat. PMID- 22063421 TI - Efficacy of lactic acid salts and sodium acetate on ground beef colour stability and metmyoglobin-reducing activity. AB - This study examined two concentrations (0.6 and 1.0mol) of three lactic acid salts (calcium lactate, CaL; potassium lactate, KL; and sodium lactate, NaL), with and without 0.01mol sodium acetate (n=3 replications), for effects on ground beef colour stability and metmyoglobin-reducing activity (MRA). Ground beef with CaL was least colour stable (P<0.05). Increasing CaL and NaL concentration decreased (P<0.05) colour stability. Ground beef with acetate only was most colour stable (P<0.05), but it did not result in more MRA (P>0.05) than control ground beef. Including both lactate and acetate was not as effective (P>0.05) in increasing colour stability as acetate alone. In general, both KL levels were equal (P>0.05) to the lower NaL concentration, and all three were superior in colour stability (P<0.05) to CaL and the higher NaL concentration. More MRA was generated by including lactates (P<0.05); KL and NaL had more MRA than CaL (P<0.05). However, these increases in MRA did not result in improved colour stability. Overall, adding KL to ground beef would not increase ground beef colour stability over adding nothing, but CaL and high levels of NaL would decrease colour stability. Using 0.01mol sodium acetate maximized ground beef colour stability. PMID- 22063422 TI - The influence of creatine and a high glycemic carbohydrate on the growth performance and meat quality of market hogs fed ractopamine hydrochloride. AB - Crossbred barrows (n=128; 85+/-0.91kg) were randomly allotted to one of four dietary treatments. A pelleted corn-soybean diet containing 5ppm Paylean((r)) (PAY) was tested against a negative control (NCON) diet formulated to meet or exceed the National Research Council's requirements for the growing pig, a pelleted corn-soybean diet containing 0.92% creatine and 2.75% dextrose (COMBO), and a pelleted corn-soybean diet containing a combination of 5ppm Paylean((r)), 0.92% creatine, and 2.75% dextrose (PAYPLUS). No treatment differences were noted when comparing ADG (P=0.66) and hot carcass weight (P=0.75). Over the 27d test, barrows fed PAY and PAYPLUS produced loins with a larger (P<0.01) loin muscle area (LMA) than those fed NCON or COMBO diets. Barrows fed the NCON diet were fatter at the 10th-rib (P<0.01) than those animals fed the remaining dietary treatments. Dietary treatment did not affect the ultimate pH (P=0.87), Japanese color score (P=0.25) or Minolta L(*) (P=0.61) and b(*) (P=0.56) values of the loin. Loin chops from NCON, COMBO and PAYPLUS tended (P=0.07) to contain a higher intramuscular fat content than those from barrows fed PAY. Additionally, loin chops from the NCON and COMBO fed animals were more red (higher a(*)-value) than those chops coming from animals fed the PAY diet (P<0.01). PMID- 22063423 TI - Effects of oral vitamin D(3) supplementation and supplement withdrawal on the accumulation of magnesium, calcium, and vitamin D in the serum, liver, and muscle tissue and subsequent carcass and meat quality of Bos indicus influenced cattle. AB - Bos indicus crossbred cattle (n=79) were fed vitamin D(3) (0 or 3 million IU/hd/d) for 5d. Afterwards, half of each group was slaughtered immediately, while half was fed, without supplementation, for 7d before processing. Serum calcium concentration was increased (P<0.05) in cattle after supplement removal, but not immediately following supplementation. This also was observed in the M. longissimus lumborum and M. triceps brachii, but not in the M. semitendinosus. Liver biopsy vitamin D(3) concentrations were higher (P<0.05) in supplemented cattle immediately following supplementation, but were not different from controls after supplement removal. Vitamin D(3) did not affect tenderness at supplement removal day 0, but increased the tenderness of the M. longissimus lumborum and M. semitendinosus at supplement removal day 7. Vitamin D(3) supplementation improves muscle tenderness and may be more effective when supplementation is ceased 7d before slaughter, with minimum food safety concerns. PMID- 22063424 TI - Conjugated linoleic acid content of beef differs by feeding regime and muscle. AB - The project objective was to determine the CLA content of three muscles (Longissimus lumborum, LD; Semimembranosus, SM; Triceps brachii, TB), in both raw and cooked states, in cattle finished on pasture or with grain supplements. Cattle were randomly assigned to one of four finishing regimens; pasture (n=11), pasture with grain supplement (n=11), pasture with grain supplement containing soyoil (n=12), and feedlot (n=12). In the raw state, TB had higher (P<0.05) CLA than LD or SM on a mg/g sample basis. Total CLA was higher (P<0.05) in the soyoil diet when compared to the other three feeding regimes on a mg/g sample basis and when expressed as mg/g fat in both raw and cooked analyses. Pasture inclusion produced higher levels (P<0.05) of total CLA than the feedlot diet on a mg/g fat basis for cooked samples while maintaining acceptable eating quality. PMID- 22063425 TI - Feral goats in Australia: A study on the quality and nutritive value of their meat. AB - The purpose of this study was to determine the quality of fresh and cooked meat, and the nutritive value of this meat from 62 male Australian feral goats. The goats were slaughtered at 5, 10, 20, 30, 40, 50, 60 and 70kg liveweights. Half of the goats were castrated and half were left as intact animals. The quality profiles of meat (e.g. pH, colour, pigment concentrations, cooking loss, shear force value and eating quality of cooked meat) from both castrated and intact feral goats started to decrease when animals were slaughtered at heavier liveweights (e.g. above 40kg). The nutritive value of the meat (chemical compositions, fatty acids and total cholesterol concentrations) changed when animals were castrated and had heavier slaughter weights. Overall, we recommend that 40kg liveweight is the heaviest slaughter weight, since the quality characteristics of meat will be lower when feral goats were slaughtered above 40kg liveweight. PMID- 22063426 TI - The application of collagen preparations as carriers of rosemary extract in the production of processed meat. AB - The application of collagen preparations as carriers of rosemary extract in the production of wiener-type and liver sausages has been evaluated. The rosemary extract was introduced into the meat products using one of two carriers (collagen hydrolyzate or collagen fibre preparation) or directly (i.e. using no carriers). The relationship between the methods of extract introduction and its antioxidative action was assessed on the basis of the lipid oxidation (i.e. determination of peroxide value and TBARS) during cold storage of sausages in air or in vacuum. The introduction of rosemary extract to the products via the collagen fibre preparation limited lipid oxidation greater than the direct addition of the antioxidant to both meat products, irrespective of storage. On the contrary, in the case of the application of collagen hydrolyzate as a carrier of extract, a masking effect was observed, diminishing the antioxidative impact on the tested products. PMID- 22063428 TI - The biochemical and physical effects of electrical stimulation on beef and sheep meat tenderness. AB - Application of electrical stimulation in the sheep and beef processing industry has been erratic around the world and this may reflect an incomplete knowledge of how to optimise the technology. Although it is well established that stimulation increases the rate of post-mortem glycolysis, other biochemical and biophysical effects have been implicated with the use of this technology. This review seeks to examine the current theories about the effect of stimulation on post-mortem muscle. The classical view that stimulation prevents muscle from shortening excessively during rigor development has been expanded to include the possibility that it also results in physical disruption of muscle structure. The interaction of these effects with the acceleration of the rate of proteolysis through activation of the calpain protease system has not been comprehensively reviewed in the past. Thus there are two mechanisms which could explain the effect of stimulation on tenderisation, reduced 'cold-induced' shortening and alteration of protein structure. A secondary effect is the enhancement of the rate of proteolysis stimulated by release of Ca (2+) at a higher temperature. As a result of this review we highlight several areas that may prove fruitful for further research. The challenge for further development of electrical stimulation systems is optimisation of the activation of the enzyme systems in parallel with manipulation of chilling regimes so as to ensure rigor mortis is achieved at temperatures which minimise shortening. These optimal temperatures largely established at a fixed incubation temperature for detached muscle may be different when measured in intact carcasses. The potential of regional stimulation of sections of the carcass to achieve this outcome is worthy of study given the different fibre composition of muscles and temperature gradients. In addition, to ensure that appropriate amounts of energy are applied to individual carcasses, development of self-response stimulation units, which are able to determine carcass resistance and apply appropriate durations or strengths of stimulation is worthy of future research. This would lead to more effective electrical stimulation practices. PMID- 22063429 TI - Carcass traits of Rambouillet and Merino * Rambouillet lambs and fatty acid profiles of muscle and subcutaneous adipose tissues as affected by new sheep production system. AB - Rambouillet and Merino*Rambouillet lambs were assigned to production systems varying in physical environment and diet: RF (raised-floor, open-sided barn/85% oat hay-10% wheat-5% molasses), FL (feedlot/high-concentrate), and P (pasture/grazing plus supplement). Although treatment duration was varied to produce similar final weights, RF lambs were heavier than P lambs, but dressing percentages were similar. Backfat thickness was less with P and for Merino cross lambs. RF feed was higher in saturated fatty acids (SFA) percentage than FL feed and P supplement, but lower compared to pasture plants. For both breed types, muscle tissue from RF was higher in SFA and lower in polyunsaturated fatty acids (PUFA) percentage than that from FL or P. In adipose tissue, SFA and PUFA tended to be higher and monounsaturated fatty acids were lower with RF for Merino cross lambs. Nevertheless, 16:0 or 18:1 percentage differences among P, FL and RF lamb tissue samples were minor vs. large variations among their respective diets. PMID- 22063430 TI - Effects of sheep production systems on oxidative storage stability of lean lamb patties. AB - Rambouillet lambs were assigned to three production systems varying in physical environment and diet: RF (a new, raised-floor feeding structure, with animals fed a pelleted mixture of 85% oat hay, 7.5% barley and 7.5% molasses); FL (a feedlot, with animals fed high-concentrate rations); and P (a pasture, with animals given access to the pasture and a high-concentrate supplement). Lengths of time on feed were adjusted to produce similar final shorn weights for each system. Ground meat patties were made with knife-separable lean from hind legs and aerobically refrigerated. Fat content of patties was not significantly different between RF and FL or P, while total unsaturated fatty acid percentage was slightly lower (P<0.05) for RF treatment. Patty color (redness) was most stable for RF. Lipid oxidation in raw patties also was lower (P<0.05) for RF than FL, but oxidation in cooked patties was greater for RF. PMID- 22063431 TI - Prediction of technological quality (cooking loss and Napole Yield) of pork based on fresh meat characteristics. AB - In order to investigate if cooking loss and Napole Yield can be predicted from various fresh meat characteristics, pH (1, 15, 30, 60, 120 min and 24 h post mortem), temperature (1, 15, 30, 60, 120 min and 24 h post mortem), water-holding capacity (Honikel's drip loss method and centrifugation loss), and NMR T2 relaxation 24 h post mortem were measured in fresh porcine M. longissimus dorsi from 102 Hampshire crossbreeds of known RN(-) genotype. Subsequently, cooking loss and Napole Yield were determined on cooked and cured, cooked samples, respectively, and partial least squares regression (PLS) was carried out to investigate possible intercorrelations between the physico-chemical measurements performed on the fresh meat and cooking loss/Napole Yield. Significant correlations were found between NMR T2 relaxation measured in fresh pork 24 h post mortem and the cooking loss (R=0.64) and Napole Yield (R=0.58), whereas no correlations were found between traditionally applied methods such as pH measurements, Honikel's method and centrifugation, and the cooking loss/Napole Yield. Consequently, it is concluded that NMR T2 relaxation characteristics of fresh pork in contrast to traditional fresh meat characteristics contain information about factors of importance for cooking loss/Napole Yield from cooked uncured/cured pork. The result implies that low-field (LF) NMR data from fresh meat reflects information about water compartmentalisation and mobility that is partly decisive for subsequent heat-induced changes of importance for the distribution of water within the cooked meat. In addition, the obtained results show that LF NMR data measured on fresh meat also seems to contain information about the inherent water of importance for the technological characteristics of the meat even when the meat is cured before cooking. PMID- 22063432 TI - Determination of fatty acids in the subcutaneous fat of Iberian breed swine by near infrared spectroscopy (NIRS) with a fibre-optic probe. AB - A near infrared spectrometer equipped with a standard 1210/210 bundle remote reflectance fibre-optic probe, with a 5*5 cm quartz window, was used for the determination of fatty acids in the subcutaneous fat of Iberian pigs. A comparative study was made of the determination of fatty acids (C14:0, C16:0, C18:0, C18:1, C18:2, C18:3, C20: 1, Sigmapolyunsaturated, Sigmamonounsaturated and Sigmasaturated) in samples of subcutaneous fat from Iberian pigs by direct application of the fibre-optic probe on samples of whole subcutaneous fat and with cam-lock cups, assessing extracts of total lipids with diethyl ether. The regression method employed was modified partial least squares (MPLS). Calibration of 157 samples, using the fibre optic probe, allowed determination of fatty acids in the following ranges: C14:0 (0.78-1.77), C16:0 (15.87-29.74), C18:0 (4.61 15.90), C18:1 (43.50-61.27), C18:2 (2.03-13.94), C18:3 (0.13-1.14), C20:1 (0.45 2.32), Sigmapolyunsaturated (2.31-14.82), Sigmamonounsaturated (47.37-65.62), Sigmasaturated (22.09-47.31), with corrected standard errors of prediction SEP(C) of 0.093, 0.56, 0.67, 0.94, 0.42, 0.10, 0.20, 0.46, 0.94, 0.83, respectively. The robustness of the method using the fibre-optic probe was tested in a slaughterhouse using 23 samples for external validation, giving multiple correlation coefficients (RSQ) for C14:0, C16:0, C18:0, C18:1, C18:2, C18:3 C20:1, Sigmapolyunsaturated, Sigmamonounsaturated, Sigmasaturated acids of 0.72, 0.94, 0.72, 0.79, 0.88, 0.55, 0.17, 0.88, 0.74, and 0.90, respectively, and a corrected standard error of prediction [SEP(C)] for these acids (%) of 0.11, 0.60, 0.84, 1.20, 0.77, 0.11, 0.30, 0.76, 1.21, and 1.18, respectively. PMID- 22063433 TI - Consumer attitudes towards beef and acceptability of enhanced beef. AB - The objective of this study was to evaluate consumer quality characteristics of enhanced steaks and roasts derived from cattle supplemented with vitamin E during finishing, and to assess the attitudes of these consumers towards beef. Twelve steers were fed either a control (E-) diet or a diet supplemented with dl-alpha tocopheryl acetate (E+). Paired strip loins and rounds were either used as controls (C) or were pumped (P) to 110% of raw weight to contain 0.4% sodium chloride and 0.4% sodium tripolyphosphate in the final product. Consumers (n=103) evaluated roasts and steaks for juiciness, tenderness, saltiness, and overall acceptability on a 9-point hedonic scale. Enhanced steaks and roasts were more acceptable than non-enhanced controls; E+ steaks were less acceptable than E- steaks. A beef quality questionnaire revealed that color, price, visible fat and cut were the most important factors underlying beef steak purchase, while tenderness, flavor and juiciness were weighted most heavily with regard to eating satisfaction. PMID- 22063434 TI - The interaction between calpastatin and RYR1 genes for some pork quality traits. AB - This study was performed in order to investigate a relationship between polymorphism's of calapastatin gene (CAST) identified with HinfI, MspI and RsaI restriction endonucleases in pigs and meat quality characteristics and also interactions between CAST and RYR1 genes. Investigations were carried out on group of 89 fatteners being crosses of (Polish Large White*Polish Landrace)*(Hampshire*Pietrain). Some meat quality characteristics, glycolytic potential of LL muscle, yield of curing meat in cooking, the yield of loin in curing and smoking processes were determined. Statistically significant influence of RYR1 genotype (CC and CT) on investigated traits wasn't affirmed. A significant effect of CAST genotype on the value of several meat quality traits was noticed. Interactions between RYR1 and CAST genes were statistically significant for pH(45) value (CAST/RsaI*RYR1) and for drip loss (CAST/HinfI*RYR1). Obtained results showed that glycogen level in LL muscle in 45 min post mortem depends on CAST/MspI and CAST/RsaI genotypes while glycolytic potential depends on CAST/RsaI genotype. Genotyp AA at CAST/RsaI locus and AA genotype at CAST/HinfI locus stopped disclose of effect of RYR1 gene mutation for pH(45) in LD muscle and for drip loss respectively. Animals heterozygous in RYR1 locus (CT) being BB homozygotes at CAST/RsaI locus produced meat with highest pH(45) value (6,4) and dark meat colour. For technological properties of meat most interesting are double heterozygotes at the loci RYR1 and CAST/HinfI with significantly lowest (P?0.01) drip loss (4,04%). PMID- 22063435 TI - Consumer and sensory investigations in relation to physical/chemical aspects of cooked pork in Scandinavia. AB - The present study addresses sensory quality and liking for pork (eight samples) varying in quality due to adrenaline injection resulting in elevated ultimate pH post-slaughter (24h), meat ageing, cooking temperature and warmed-over flavour (WOF) among consumers (n=288) in Scandinavia. The consumers preferred meat with higher pH (pH(24h)=6.0), cooked to the lowest temperature (65 degrees C versus 80 degrees C). Consumers least preferred samples with WOF described as metallic, acidic and off-flavour by a trained panel. "Elevated pH(24h) meat" cooked to 65 degrees C resulted in a more sweet and tender meat. Juiciness, tenderness and the absence of off-flavour were the most important characteristics for consumers' liking of pork. Consumption frequency and liking of pork were positively related. The consumers that were most satisfied with pork quality reported highest consumption frequency. Elderly people and males expressed the highest liking score and consumption frequency, respectively. PMID- 22063436 TI - Konjac/gellan gum mixed gels improve the quality of reduced-fat frankfurters. AB - Mixed gels of konjac (1%, 2%) and gellan gum (0.25%, 0.5%) were incorporated into reduced-fat (18%) frankfurters and compared with reduced-fat and high-fat (28%) controls for physicochemical, textural, sensory properties and storage stability. C28 (control at 28% fat) had the highest (P<0.05) lightness (L*) and yellowness (b*) values but the lowest redness (a*). C28 had the lowest textural hardness, shear force value and sensory firmness but highest juiciness scores. Treatments containing konjac/gellan gum mixed gels were not different from C28 in sensory overall acceptability, among them K1G5 (1% konjac/0.5% gellan gum) was numerically higher. C18 had the highest TPC (~7.8 log CFU/g) after 12 weeks of storage, followed by gum-containing treatments. In conclusion, it appears feasible to incorporate konjac/gellan gum mixed gel at current levels to reduced fat frankfurter for acceptable sensory merits with reasonable shelf life. PMID- 22063437 TI - Spinal cord tissue detection in comminuted beef: comparison of two immunological methods. AB - Two commercial immunological kits for detection of central nervous system (CNS) tissue in beef were compared: ScheBo(r) BrainosticTM, based on CNS-specific antigen (neuron specific enolase) detection, and Ridascreen(r) Risk Material 10/5 test, an enzyme immunoassay for glial fibrillary acidic protein. Spinal cord (SC) was added to batches of choice, select, and utility grades of ground fresh beef shoulder clod to yield 0.0, 0.0125, 0.025, 0.05, 0.1, 0.2, 0.4, 0.8, and 1.6% SC in meat. Sensitivity and specificity in detecting SC in fresh and frozen samples were determined. Both BrainosticTM and Ridascreen(r) kits detected SC at claimed levels: 0.25% and 0.11%, respectively. The Ridascreen(r) test consistently detected SC at 0.025%, below its claimed sensitivity level, expressed for brain and SC combined. The Ridascreen(r) test was ~10* more sensitive, easier, faster to run and less expensive than the BrainosticTM. Overall, quality grade had no influence on SC detection in fresh or frozen meat. PMID- 22063438 TI - Isotachophoretic determination of added phosphate in meat products. AB - From the phosphate content in meat and meat protein a new ratio of free (non protein) phosphate/protein (16+/-2 mg/g) was calculated. From the level of soluble phosphate determined by capillary isotachophoresis (CITP), protein content determined by Kjeldahl method and with the use of the earlier-mentioned ratio the amount of added phosphates could be calculated. The method was compared with the spectrophotometric dry-ashing reference method on 34 samples and good agreement was found. PMID- 22063439 TI - The effect of quantity and timing of brine addition on water binding and textural characteristics of cooked beef rolls. AB - The combined influence of quantity and timing of water/sodium chloride/phosphate addition on quality characteristics of beef rolls processed with 25 or 50% brine level was investigated. Properties of beef rolls were determined by measuring hydration and textural characteristics. The higher level of brine addition (50%) had detrimental effects on product water binding and textural characteristics. Late addition of brine/water during tumbling (i.e. during the last hour) resulted in rolls which were less hard, chewy and elastic, and had poorer water holding properties. Addition of brine in two parts favourably affected hydration properties and thermal stability, yielding lower cooking loss and purge and higher WHC, irrespective of level of brine addition. It also increased hardness and chewiness and improved springiness, cohesiveness and bind of cooked beef rolls. PMID- 22063440 TI - Conservation of Cervus elaphus meat in modified atmospheres. AB - This study examines the effect of three types of modified atmospheres, each with a different gas composition (A:40% CO(2)+60% N(2); B:80% CO(2)+20% O(2); C:80% CO(2)+20% N(2)), on the development of meat quality of Cervus elaphus in order to suggest a gas composition that best preserves this type of meat. Meat quality was assessed by examining pH, colour as L(*)a(*)b(*) values, drip loss (DL), cooking loss (CL) and shear force (SF). In samples of group A, pH values tended to be higher in all storage periods than those packed with 80% CO(2) and significant differences (P<0.001) among the groups were found at 16 d of storage. Gas composition affected a(*) and b(*) parameters (P<0.001), in samples packed with O(2), the b(*) values were higher than in other groups, while the opposite was true in a(*) values. Similar values of DL and CL were observed for all treatments and both parameters increased over time. SF values decreased with ageing, with similar values observed for all treatments. PMID- 22063441 TI - Consumer sensory evaluation of plain and seasoned goat meat and beef products. AB - Plain meat loaves and chili were prepared with ground goat meat or beef containing 15% fat. A consumer sensory panel first rated meat loaf samples for acceptability on a 9-point hedonic scale. Then, meat loaf samples, followed by chili samples, were each evaluated in triangle test for differentiation between goat meat and beef. Acceptability scores were similar for plain goat meat and beef loaves when the goat meat product was served before the beef product, but were lower for the goat meat with reverse serving order. In triangle tests, goat meat was differentiated from beef, whether plain or seasoned products. PMID- 22063442 TI - The influence of the rate of pH decline on the rate of ageing for pork. I: interaction with method of suspension. AB - The influence of the rate of pH decline post slaughter on the rate of ageing of pork was investigated. The rate of pH decline on 24 finisher pigs was manipulated by altering the method of stunning (carbon dioxide or electrical head to heart) and by the use of electrical stimulation (none or low voltage electrical stimulation (LVES) at 4 min post slaughter). To investigate the effect of pH decline rate on ageing rate independently of the effect on possible muscle shortening, sides were suspended by either the pelvis (to minimize shortening) or conventionally by the Achilles tendon. The data indicated that the rate of pH decline did not influence the rate of ageing but the use of LVES did improve tenderness at 1, 2 and 10 days post slaughter due to the prevention of muscle shortening. Electrical stunning improved tenderness at 1 and 2 days post slaughter but had a detrimental effect on drip loss. Pelvic suspension improved tenderness at rigor, 1, 2 and 6 days post slaughter due to prevention of muscle shortening. The conditions employed however were not severe enough to induce protein denaturation. PMID- 22063443 TI - The influence of the rate of pH decline on the rate of ageing for pork. II: Interaction with chilling temperature. AB - The influence of the rate of pH decline post slaughter on the rate of ageing of pork m. longissimus thoracis et lomborum was investigated. The rate of pH decline on 24 finisher pigs was manipulated by altering the method of stunning (carbon dioxide or electrical head to heart) and by the use of electrical stimulation (none or low voltage electrical stimulation (LVES) at 4 min post slaughter for either 15 s or 60 s). The rate of temperature decline was altered by chilling at 2 or 14 degrees C until rigor. The pH and temperature decline rates generated were designed to induce cold shortening at one extreme and protein denaturation at the other. The research results showed that the rate of pH decline was increased by electrical stimulation which in turn reduced cold shortening and improved tenderness. Chilling at 14 degrees C reduced the time to reach rigor by 1.3 h and resulted in a faster aging rate as indicated by a larger percentage change in WBSF from rigor to 4 days postmortem relative to carcases chilled at 2 degrees C. The greater tenderising effect appeared to be due to a combination of prevention of cold shortening and increased proteolysis. However, chilling slowly at 14 degrees C or the use of LVES for 60 s or any combination of these treatments did not induce protein denaturation. PMID- 22063444 TI - The effect of replacing fat with oat bran on fatty acid composition and physicochemical properties of meatballs. AB - Oat bran was used as a fat substitute in the production of meatballs. The effect of oat bran addition on the fatty acid composition, trans fatty acids, total fat, some physicochemical and sensory properties of the samples was studied. Meatballs were produced with four different formulations; the addition of 5, 10, 15 and 20% oat bran. Control samples were formulated with 25% fat addition as in commercial production. The major fatty acids were cis-oleic, palmitic and stearic acid in all the meatball samples, those with oat bran added as well as the control. Meatballs containing oat bran had lower concentrations of total fat and total trans fatty acids than the control samples. Meatballs made with 20% oat bran had the highest protein, salt and ash contents, L value (lightness), b value (yellowness), and the lowest moisture content and a value (redness). There was no significant difference among the meatball samples with respect to sensory properties, and all samples had high acceptability. PMID- 22063445 TI - Comparison of the performances of Nero Siciliano pigs reared indoors and outdoors. 1. Growth and carcass composition. AB - A total of 78 female and male Nero Siciliano pigs were used. Forty-one pigs were reared following the traditional management system, 37 pigs were reared in pens with a small outdoor paddock and fed to appetite using commercial rations according to the growing period. Both male and female pigs were castrated. All pigs were weighed and measured periodically. Body measurements included height at withers, chest girth, body length, width at shoulders and at rump. Age and body weight at slaughter ranged respectively from 371 to 572 days and from 79 to 113 kg. The carcasses were weighed and dissected into lean, fat and bone cuts. In the early and final stages indoor-pigs grew faster than those reared outdoors. Trends in body length were similar for the two rearing systems, for width at shoulders and rump, chest girth and height at withers, indoor pigs showed higher values than the outdoor ones. Carcasses of similar weight were longer in outdoor than in indoor pigs but the latter showed greater subcutaneous fat thickness. Outdoor pigs had the lowest dressing percentage and the highest percentage of lean cuts, such as shoulder and ham, but not of neck and loin. Sex did not significantly affect the analysed characteristics. PMID- 22063446 TI - Effect of sodium chloride replacement on some characteristics of fermented sausages. AB - The reduction of added NaCl in fermented meat products has been proposed to decrease the amount of sodium in the diet. The effect of substituting NaCl by KCl, potassium lactate (K-lactate) or glycine (0-40%) in some sensory, microbiological and physicochemical characteristics of fermented sausages was evaluated. The sensory effects of substituting NaCl by mixtures of glycine and KCl or glycine and K-lactate was also evaluated. The partial substitution of NaCl by KCl, K-lactate and glycine had little effect on microbiological stability. However, flavour and/or textural defects were detected by sensory analysis with substitution levels of 40% by KCl, 30% with K-lactate and 20% with glycine. The partial substitution (above 40%) of NaCl with different mixtures of KCl/glycine and K-lactate/glycine showed important flavour and textural defects which did not permit an increase in the level of substitution compared to those obtained with the individual components. PMID- 22063447 TI - Effects of cooking method, reheating, holding time, and holding temperature on beef longissimus lumborum and biceps femoris tenderness. AB - Effects of cooking method, holding temperature, holding time, and reheating on Warner-Bratzler peak shear force (WBPSF); Warner-Bratzler myofibrillar force (WBM F), Warner-Bratzler connective tissue force (WBC-F) and cooking loss were investigated. Two muscles (longissimus lumborum and biceps femoris) from USDA Choice beef carcasses were used. Water-bath cooking resulted in higher WBPSF, WBM F, and WBC-F than belt-grill cooking for longissimus lumborum. The biceps femoris muscle tenderness improved more with holding time after cooking on a belt than the longissimus lumborum due to its higher collagen content. Cooking biceps femoris steaks to 54 degrees C by a belt grill and holding them at 57 degrees C in a water bath for 15 min and subsequent reheating to 70 degrees C (best treatment combination) produced a 25% reduction in WBPSF, a 37% reduction in WBC F, and a 12% reduction in WBM-F as compared to the control (cooking steaks directly to 70 degrees C without holding). Water-bath cooking resulted in lower WBPSF than belt-grill cooking for biceps femoris without any holding time, but further tenderization did not occur with holding. Water-bath cooking resulted in higher cooking losses than belt-grill cooking for both muscles. PMID- 22063448 TI - Effect of level, source, and time of feeding prior to slaughter of supplementary dietary magnesium on pork quality. AB - A total of 192 pigs were utilized in a 2*3*3 factorial arrangement with an additional control treatment. The treatments were: (1) magnesium level (1.6 vs. 3.2 g of magnesium pig(-1) day(-1)); (2) magnesium source (sulfate vs. proprionate vs. proteinate); (3) feeding duration (5 vs. 2 vs. 1 day), and a control (no supplementary magnesium). Minolta L(*) values were lower (P?0.05), indicating darker muscle color, for pigs supplemented with 1.6 g magnesium pig( 1) day(-1) compared to the controls while pigs on the 3.2 g magnesium level were intermediate between these two treatments. Animals on the 1 day treatment had a higher (P?0.05) ultimate pH and lower (P?0.05) Minolta L(*) compared to those on the 2 days and control treatments, while 5 days pigs were intermediate and had lower L(*) values compared to the controls. The sulfate and proteinate treatments produced pork with the lower (P?0.05) Minolta L(*) values compared to the controls. Pigs fed the sulfate diet had a lower (P?0.05) drip loss compared to those on the control treatment. Results from this study suggest that the lowest level (1.6 g magnesium pig(-1) day(-1)) and the shortest time of supplementation (1 day) may be effective in improving pork color and water-holding capacity. PMID- 22063449 TI - Characterization of lactic acid bacteria isolated from a Greek dry-fermented sausage in respect of their technological and probiotic properties. AB - A total of 147 lactic acid bacteria was isolated from two types of naturally fermented dry sausages at four different stages of the ripening process studied in order to select the most suitable strains according to their technological characteristics including probiotic properties and antimicrobial activity against food-borne pathogens. Identification of the isolates revealed that 90% were lactobacilli, 4% enterococci, 3% Pediococcus sp. and sporadic isolates of Weissella viridescens, Leuconostoc pseudomesenteroides, and Leuconostoc sp. The isolated strains of Lactobacillus sakei (49 isolates), Lactobacillus curvatus (24 isolates) and Lactobacillus plantarum (7 isolates) were further characterized. All strains could grow at 15 degrees C, whereas the majority of the strains was able to grow in the presence of 6.5% NaCl and on acetate agar. The enzymatic potential of the strains was evaluated using the API ZYM system. During in vitro investigations all strains exhibited high leucine and valine aminopeptidase activities and moderate acid phosphatase and phosphohydrolase activities. Some strains showed very weak lipolytic activity. The enzyme profiling is an important factor for selection of strains as starter cultures. A large majority of the strains tolerated 0.1% bile salts whereas 58% of Lactobacillus curvatus strains and all Lactobacillus plantarum strains were resistant to 0.3% bile salts. All Lactobacillus sakei strains and the majority of Lactobacillus curvatus and Lactobacillus plantarum strains exhibited an anti-listerial activity against three Listeria monocytogenes strains. A percentage of 75, 50 and 29% of Lactobacillus sakei, L. curvatus and L. plantarum strains, respectively, could inhibit two Staphylococcus aureus strains. The contribution of the selected strains to a possible inhibition of Listeria monocytogenes and S. aureus in situ on fermented meats would be of considerable interest to enhance the hygienic quality of these products. PMID- 22063450 TI - Quality characteristics of low fat ostrich meat patties formulated with either pork lard or modified corn starch, soya isolate and water. AB - A trained taste panel could not distinguish (P>0.05) between ostrich meat patties containing either 10% pork lard or 10% of a modified starch/protein isolate (fat replacer) mixture. The panel could distinguish between the types of ostrich muscle/meat cuts used with a significant (P<0.05) number preferring ostrich patties made from meat containing a higher collagen content (+/-3% vs <1%). The chemical analysis of the patties showed that within the meat classes (Class fillet-de-membraned, Class A-very lean off-cuts and Class B-off-cuts containing visual connective tissue and some fat), the patties containing the pork fat had a +6% higher total fat content than those containing the fat replacer. The fatty acid profiles of the various products were in accordance with the meat type and fat or fat replacer used. The mineral profile was as expected for lean ostrich meat that had spices added. It is concluded that fat replacers can be used successfully for the production of low fat ostrich patties without any negative quality attributes being perceived. PMID- 22063451 TI - Effect of the fungal extracellular protease EPg222 on texture of whole pieces of pork loin. AB - Proteolytic activity of the fungal protease EPg222 and its effect on texture has been investigated in a meat model system based on sterile pieces of pork loins incubated for 32 days. SDS-PAGE analysis of treated samples showed intense hydrolysis of the myofibrillar proteins H-meromyosin, T-troponin, tropomyosin and the proteins bands of 98, 89, 48, 39, 37 and 28 kDa after 17 days of incubation. Proteolytic activity of the enzyme led to a higher accumulation of NPN in treated than untreated samples. Microstructural analysis of muscle fibres showed loss of muscle fibre structure only in treated batch. The texture profile analysis reveals lower values in hardness, gumminess and chewiness in treated than control batch. This effect may be of great interest in dry-cured meat products to counterbalance the increase of hardness reported in these products as consequence of protein denaturation. PMID- 22063452 TI - Lipid, instrumental color and sensory characteristics of ground beef produced using trisodium phosphate, cetylpypiridinium chloride, chlorine dioxide or lactic acid as multiple antimicrobial interventions. AB - Beef trimmings were treated with 0.5% cetylpyridinium chloride followed by 10% trisodium phosphate (CT), 200-ppm chlorine dioxide followed by 0.5% cetylpyridinium chloride (CLC), 200-ppm chlorine dioxide followed by 10% trisodium phosphate (CLT), or 2% lactic acid followed by 0.5% cetylpyridinium chloride (LC). The trimmings were ground, packaged and sampled at 0, 1, 2, 3 and 7 days of simulated retail display and compared with an untreated control (C) for instrumental color, sensory color and odor and TBARS (Thiobarbituric acid reactive substances) characteristics. Ground beef from the LC and CLC treatments were lighter (P <0.05; L*) than C. The LC and CT ground beef samples were similar (P > 0.05) in vividness to C. On day 3, CT was scored redder (P <0.05) than C. Therefore, the use of CT, CLT, CLC and LC had little impact on ground beef color and CT improved ground beef color shelf life. PMID- 22063453 TI - Physicochemical and sensory characterisation of Morcilla de Burgos, a traditional Spanish blood sausage. AB - Morcilla de Burgos is a popular cooked blood sausage produced in the region around Burgos in the north of Spain. Physicochemical and sensory properties of this traditional product were investigated in order to support the claim for a Protected Geographical Indication. Products from 14 manufacturers were analysed for pH, water activity (a(w)), moisture, ether-extractable fat, starch, protein, total sugar, ash, iron and sodium contents as well as sensory parameters related to visual, olfactory, texture and flavour attributes. Principal component analysis confirmed the existence of three varieties of Morcilla de Burgos. Morcillas from group I were characterised by a notable blood smell and blood and pepper flavour, a high pH, and a(w) and a high protein content. Morcillas from group II were characterised by strong cumin smell and flavour and a high softness. Morcillas from group III had a high onion odour, high presence of onion and high contents of fat, total sugar and fibre. PMID- 22063454 TI - Effect of transglutaminase-induced cross-linking on gelation of myofibrillar/soy protein mixtures. AB - Microbial transglutaminase (MTGase)-catalyzed interaction and gelation of mixed myofibrillar (MPI)/soy (SPI) protein isolates were investigated at varying ionic strengths and MPI:SPI ratios, with or without SPI being preheated (80 degrees C). MTGase treatments in deionized water converted myosin heavy chain and actin into lower molecular-weight polypeptides, which gradually diminished as the ionic strength increased up to 0.6 M NaCl. A reduced intensity in the electrophoretic bands of soy proteins (7S and 11S except the basic subunits) was observed in all treatments, suggesting cross-linking with MPI. The enzyme treatment slightly increased the thermal transition (denaturation) temperatures of MPI/SPI but greatly enhanced (P<0.05) the elasticity of the mixed protein gels when compared with untreated samples, independent of incubation time. PMID- 22063455 TI - Evaluation of pork colour: prediction of visual sensory quality of meat from instrumental and computer vision methods of colour analysis. AB - M. longissimus dorsi minced pork patties from three dietary treatment groups of DLY (Duroc/Landrace/Yorkshire) cross bred pigs were packaged in polythene bags and placed in a retail refrigerated display cabinet at 5 degrees C+/-1 degrees C, under fluorescent light (1000 lux) for up to 5 days. Each dietary treatment group consisted of pigs (n=7) fed either a low vitamin E diet (80 mg dl-alpha tocopheryl acetate/kg of feed), supplemental iron (7 g iron (II) sulphate/kg feed) or supplemental vitamin E (200mg dl-alpha-tocopheryl acetate/kg of feed) + supplemental iron). Samples were subjected to visual colour evaluation by a trained sensory panel (n=8) and an untrained panel (n=8) on days 0, 1, 3 and 5. Instrumental Hunter L(*), a(*) and b(*) values were measured on each day of analysis using a Minolta colorimeter. In addition RGB (red, green and blue) and Hunter L(*), a(*) and b(*) values were measured using a digital camera. The use of trained and untrained panellists are both relevant in the visual assessment of meat products. In a previous study O'Sullivan, Byrne, and Martens (2003) indicated that the untrained panellist is analogous to the consumer and how they perceive colour changes in meat. However, the trained panellist is useful in the assessment of unfamiliar products and where a greater degree of discrimination is required. The order of oxidation of the experimental treatments was Control (low vitamin E) 0.05), but were negatively correlated with a* and b* values (P<0.05). The "in home" portion of this study consisted of 47 households that prepared and evaluated chops randomly distributed by category. Consumers reported differences in liking of juiciness and liking of tenderness (P<0.05) due to color category. Eighty-nine percent of the households participated in a simulated retail display where, 20.8% chose chops from category A, 26.4% from category B, and 52.8% from category C. A trained panel evaluated the cooked chops and perceived category C to be more tender, more juicy, and less dry than both A and B (P<0.05). Consumers responded similarly to the trained panel in their perceptions of tenderness and juiciness. PMID- 22063458 TI - Self-reported psoriasis severity and quality of life assessment at Comano spa. AB - The relationship between quality of life (QoL) and skin lesion improvement due to psoriasis treatment has been recently underlined. Our objective was to study the self-reported disease severity reduction and QoL during spa treatments and identify predictors of psoriasis improvement. Patients were assessed before and after spa treatment with a disease-specific QoL questionnaire (Skindex-17) and self-administered psoriasis area and severity index (SAPASI). Their correlations were tested. Factors predicting a reduction in Skindex-17 or in SAPASI score were evaluated through regression analysis. Significant mean overall reductions in SAPASI (27%) and Skindex-17 scores (psychosocial: 6%; symptoms: 2%) were achieved. However, 51% of patients reporting SAPASI improvement also reported a worsened QoL. Pearson's correlation between the SAPASI and Skindex-17 scores was poor (r=0.26 for SAPASI-symptoms and r=0.40 for SAPASI-psychosocial). Logistic regression analysis identified the age of psoriasis onset before 30 years (OR=3.81, 95% CI 1.22-11.95, p=0.02) and a basal Skindex-17 symptoms value greater than 5 (OR=3.37, 95% CI 1.12-10.08, p=0.03) as predictive of both SAPASI and Skindex-17 score reductions. Age-of-onset-based stratification identifies the subset most likely to respond to spa treatment. Combining the Skindex-17 with SAPASI provides a more comprehensive patient-centered assessment. We recommend this assessment for psoriasis patients undergoing spa treatment. PMID- 22063459 TI - Symptom triggered screening for ovarian cancer: a pilot study of feasibility and acceptability. AB - PURPOSE: Our goal was to determine if symptom-based ovarian cancer screening was feasible in a primary care clinic and acceptable to women and practitioners. In addition, we wanted to describe the outcomes for a pilot group of screened women. METHODS: A prospective study of 2262 women over age 40 with at least one ovary participated in symptom-based screening using a symptom index (SI). The first 1001 were in a non-intervention study arm and 1261 were screened for symptoms and referred on to testing with CA125 and transvaginal ultrasound (TVS) if the SI result was positive. Patients and practitioners were surveyed about acceptability of study procedures. All patients were linked to the Western Washington SEER Cancer Registry to determine if ovarian cancer was diagnosed in any women. RESULTS: Of the eligible women visiting the clinic, 72.5% were interested in participating, and the participation rate was 62.1%. Of the 1261 who participated in the screening arm 51 (4%) were SI positive and 47 participated in CA125 (45/47 normal) and TVS (32/47 normal). Two endometrial biopsies and one hysteroscopy D&C were performed secondary to study enrollment (pathology negative). No laparotomies or laparoscopies were performed secondary to study involvement. A survey of patient acceptability, on a scale of 1-5, revealed a mean score of 4.8 for the acceptability of SI screening and 4.7 for TVS and CA125 testing among SI positive women. Providers also rated the SI procedures highly acceptable with a mean score of 4.8. Two participating patients were diagnosed with ovarian cancer; one had a true positive SI in the non-intervention arm and one had a false negative SI in the screened arm. CONCLUSION: While our pilot study is not large enough to assess sensitivity or specificity of a symptom-based screening approach, we did find that this type of screening was feasible and acceptable at the time of a primary care visit and referred approximately 4% of women for additional diagnostic testing. Symptom-based screening also resulted in minimal additional procedures. PMID- 22063460 TI - Quality of life in cervical cancer survivors: patient and provider perspectives on common complications of cervical cancer and treatment. AB - OBJECTIVE: This study's objective was to quantify the impact (utility) of common complications of early cervical cancer treatment on quality of life (QOL). Utilities assigned by survivors were compared to those assigned by providers. METHODS: 30 survivors of early cervical cancer identified from our Tumor Registry and 10 gynecologic oncology providers were interviewed. Participants evaluated complications (health states) using the standard gamble (SG) and visual analogue scale (VAS). Each participant was randomly assigned to rate 5 of 13 health states. Mixed-effects linear models were used to generate confidence intervals for utility means, and evaluate the effect of group (survivors versus providers). Higher utilities indicate the health state is closer to perfect health. RESULTS: Survivors and providers mean ages were similar (44 and 40). Mean time from diagnosis was 6.7 years. 28 of 30 survivors had no evidence of disease. 56% of survivors had complications. Using SG, providers consistently assigned utilities 7% higher than survivors (p=0.035) for all health states except "ileostomy", which survivors rated higher than providers. Survivors assigned the lowest utility to small bowel obstruction (SBO) (fixable without an ostomy) and ureteral obstruction (UO). Survivors rated SBO 16% and UO 21% lower than providers. Personal history of complications or higher stage did not have a consistent effect on QOL adjustments. DISCUSSION: Providers assign higher utilities than survivors to health states. Providers and survivors diverge on which complications impact QOL the most. Data on patient preferences should be considered when weighing treatment options with similar survival but different associated complications. PMID- 22063461 TI - Genetic polymorphisms as predictive and prognostic biomarkers in gynecological cancers: a systematic review. AB - PURPOSE: Numerous studies have explored the potential role of genetic polymorphisms as predictive or prognostic biomarkers in gynecologic malignancies. A systematic review for all eligible polymorphisms has not yet been reported. The aim of this study was to summarize the current status of the field and provide direction for future research. DESIGN: We searched literature databases (MEDLINE, EMBASE, Cochrane) from 2006 to April 2011 to identify studies evaluating the association between gene polymorphisms and clinical outcome in ovarian, endometrial, cervical, or vulvar cancer. The main outcome measures were overall survival (OS) and progression-free survival (PFS). Studies reporting relationships between polymorphisms and toxicity were also included. RESULTS: Sixty two studies met the inclusion criteria. The median sample size was 140. Most of the included studies (n=50, 81%) were conducted in ovarian cancer patients. Almost a third assessed potential predictive associations between gene polymorphism and outcome in ovarian cancer. The most commonly evaluated genes were ERCC1, VEGF, ABCB1 (MDR), and GSTP1. Most studies (n=44, 71%) were observational case-series. Only four studies (6%) included a validation arm and patient population ethnicity was explicitly stated only in 27% of included studies. CONCLUSION: No consistent association between any gene polymorphism and clinical outcome in gynecological cancers has been found across studies. There is incomplete adherence to the REMARK guidelines and inadequate methodology reporting in most studies. Moving forward, analysis of large trial-based clinical samples; adherence to the highest methodological standards, and focus on validation analyses are necessary to identify clinically useful pharmacogenomic biomarkers of outcome. PMID- 22063462 TI - A note on the influence of heat treatment, salting and smoking on the acceptability of camel meat products. AB - The present study was conducted to assess the effect of selected processing operations on the acceptability of camel meat products in Dire Dawa, eastern Ethiopia. A total of eight camel meat products were prepared at two levels of salting, smoking, frying and cooking. They were evaluated by a sensory panel using a preference test. The results showed that the fully fried samples were not significantly different in preference to the smoked (2.5% salt, 3 h smoking) samples and were more acceptable than the partly fried samples. Nevertheless, the smoked (2.5% salt, 3 h smoking) samples were preferred over the others. The fully cooked and the salted (3% salt) products were also acceptable. PMID- 22063463 TI - Dietary tea reduces the iron content of beef. AB - We hypothesized that the lightness of Japanese beef was related to the concentration of heme iron. In Experiment 1, six Japanese Black heifers were allotted randomly to one of three treatment groups: a basal concentrate ration (40% flaked corn) or the same diet and either 2 kg/d wheat bran or 0.5 kg/d green tea. After feeding the diets for 174 d, the cattle were slaughtered and the M. longissimus thoracis, M. semimembranosus, and M. gluteus medius were sampled for meat color, iron, and lipid content. The iron content of the M. semimembranosus from the tea-fed cattle was lower than in M. semimembranosus from the control cattle, and a* (redness) and ?(a(*2)+b(*2)) (saturation) values were lower in M. semimembranosus from bran- and tea-fed cattle than in control cattle. Treatment main effects (across muscles) indicated that inclusion of tea in the diet increased intramuscular lipid and reduced the muscle iron content. There was a significant negative correlation (r(2)=0.79) between muscle iron content and L(*) value (lightness). For Experiment 2, the effect of beef breed type on meat color and iron content of M. longissimus thoracis was investigated using stored meat samples from six breeds from a previous fattening experiment done under a high nutritional plane. Muscle iron content was significantly lower in Japanese Black cattle than in Japanese Black * Holstein or Japanese Black * Japanese Black/Holstein. There was no relationship between muscle iron content and intramuscular lipid content (r(2)=0.001). In Experiment 3, samples of M. longissimus dorsi were obtained from 17 Wagyu crossbred and 3 Angus crossbred cattle fed a corn concentrate diet in the USA for 148 d. Iron content of the M. longissimus thoracis from Japanese Black and Japanese Brown * Holstein cattle fattened in Japan was significantly less than the iron content of M. longissimus dorsi from cattle raised in the USA. Overall, the data indicate that it is possible to lower muscle iron, and lighten muscle color, by feeding green tea to Japanese cattle; also, there may be a genetic basis for the lower iron, and lighter color, of beef produced in Japan. PMID- 22063464 TI - An actin gene-related polymerase chain reaction (PCR) test for identification of chicken in meat mixtures. AB - Using the polymerase chain reaction (PCR) and DNA extracted from muscle, a single pair of oligonucleotide primers can yield amplification products from several members of the actin multigene family simultaneously. These multiple PCR products form species-specific "fingerprints" on gel electrophoresis which may be useful for meat authentication. However, for analysis of meat mixtures, the presence of a single band unique to a species would have many advantages over a multi component fingerprint. A procedure is described in which primers amplify at a single actin gene locus, giving a positive band with DNA extracted from chicken and turkey, but no reaction with duck, pheasant, porcine, bovine, ovine or equine DNA. The chicken signal was clearly detectable with DNA from meat admixtures containing 1% chicken/99% lamb and from meat heat-treated at 120 degrees C. For further discrimination, the chicken PCR product could be differentiated from turkey by restriction enzyme digestion. PMID- 22063465 TI - Effects of raw binder system, meat cut and prior freezing on restructured beef. AB - The effect of different meat cuts or previously frozen meat on processing properties of restructured beef bound with alginate or Fibrimex(TM) was investigated. Inside rounds, chuck tenders, chuck clods and tri-tip were used to manufacture restructured logs. Steakettes manufactured with alginate had significantly (P<0.05) higher particle bind in the raw state but Fibrimex had greater bind between meat pieces after cooking. Choice of cut or use of previously frozen meat to manufacture restructured steakettes had no effect on any of the processing parameters measured. Steakettes made with Fibrimex were lighter, redder and yellower than those made with alginate. Redness and yellowness of steakettes decreased with retail storage time. However, the change in redness and yellowness over time was similar for both binders. Use of previously frozen meat resulted in a darker, less red steakette. When alginate was used to manufacture steakettes, cut had no affect on the acceptability of steakettes. However, when Fibrimex was used steakettes made from clod and tip were preferred by a consumer panel to steakettes made from tender and inside round. PMID- 22063466 TI - Colour stability of beef from different Spanish native cattle breeds stored under vacuum and modified atmosphere. AB - Beef steaks from five Spanish cattle breeds were submitted to three packaging conditions: (a) 15 days under vacuum, (b) 15 days under modified atmosphere (MAP) (60% O(2), 30% CO(2) and 10% N(2)), and (c) 10 days under vacuum plus 5 days more under MAP. CIE L(*)a(*)b(*) coordinates, chroma (C(*)) and hue (H(*)), relative concentration of myoglobin, oxymyoglobin and metmyoglobin at the meat surface and sensory evaluation of colour were determined 0, 5, 10 and 15 days after packaging. Beef under MAP showed higher lightness (L(*)) and hue (H(*)) and lower redness (a(*)) and chroma (C(*)) than beef under vacuum. Colour of beef under MAP was not acceptable after 15 days of storage, due to the high metmyoglobin concentration. Yellowness (b(*)) was the indicator of differences due to ageing and differences in colour between breeds were related to L(*), a(*) and H(*) values. Packaging conditions had a greater effect on beef colour than breed, but breed differences might change with packaging atmosphere. Both packaging and breed are major factors in packaged beef quality. PMID- 22063467 TI - Listeria innocua and aerobic mesophiles during chill storage of inoculated mechanically recovered poultry meat treated with high hydrostatic pressure. AB - Mechanically recovered poultry meat (MRPM) was inoculated with Listeria innocua 910 CECT at a level of approximately 10(8) CFU g(-1). Vacuum-packaged samples were treated by combinations of pressure (350, 400, 450 and 500 MPa), time (5, 10, 15 and 30 min) and temperature (2, 10 and 20 degrees C) and later stored at 2 degrees C for 2 months. Counts of L. innocua and aerobic mesophilic bacteria were determined 1, 4, 7, 15, 30 and 60 days after pressurisation. For mesophiles, in most treatments, pressurization at 2 degrees C gave the significantly best results. High pressure caused a marked bactericidal effect on L. innocua: reductions higher than 7.5 log units were achieved in several cases. Some cells were just sublethally injured by pressure. Samples treated at 500 MPa for 30 min at 2 degrees C had counts of only 2.3 log units after 60 days of chill storage. Noninoculated pressurised MRPM did not show Listeria growth throughout storage. These results suggest that high pressure processing can enhance the microbiological quality of MRPM. PMID- 22063468 TI - Pork tenderness estimation by taste panel, Warner-Bratzler shear force and on line methods. AB - The extent to which modification of Warner-Bratzler shear force (WBSF) determinations, relating to storage and preparation of the meat, aperture of the V-shaped cutting blade and shearing velocity, improve the relationship with sensory tenderness perception of pork was studied. Additionally four on-line methods: pH1, FOP1 (light scattering), PQM1 (conductivity) and DDLT (Double Density Light Transmission), were evaluated for their ability to predict tenderness. Sensory tenderness evaluation was conducted on 120 frozen (at -18 degrees C for several months) samples of m. longissimus thoracis et lumborum. After overnight thawing, the meat was grilled to an internal temperature of 74 degrees C and scored on an eight-point scale, from extremely tough to extremely tender. The standard WBSF procedure (protocol A) consisted of heating fresh meat samples (stored for 48 h at 4 degrees C post slaughter) at 75 degrees C for 50 min, cooling in cold tap water for 40 min, taking cylindrical cores parallel to the fibre direction, and shearing at a velocity of 200 mm/min with a blade aperture of 60 degrees . For the prediction of sensory tenderness, the WBSF standard procedure (protocol A) showed the lowest variance (R(2)=15%) and the highest standard error of the estimate (SEE=0.97 N) compared to the other WBSF protocols. A decrease in shearing velocity, from 200 to 100 mm/min and, a replacement of the cutting blade with an aperture of 60 degrees by one with an aperture of 30 degrees led to improvements of R(2) (respectively, 19% vs. 13% and 47% vs. 23%) and SEE (respectively, 0.93 N vs. 0.97 N and 0.80 N vs. 0.97 N) and thus were better predictors of tenderness. A blade aperture of 30 degrees instead of 60 degrees also led to considerably lower WBSF values (22.1 N vs. 30.0 N). Freezing, frozen storage and thawing of the meat, prior to WBSF measurement, resulted in higher shear force values (32.7 N vs. 28.7 N) and a better prediction of tenderness, R(2) (25% vs. 15%) and SEE (0.94 N vs. 1.00 N). Furthermore, preparing the frozen stored meat for WBSF determination in the same way as for the sensory evaluation, namely grilling instead of boiling, led to higher WBSF values (35.5 N vs. 32.7 N) and a further improvement in the prediction of tenderness (R(2)=31% vs. 25% and SEE=0.90 N vs. 0.94 N). From the on-line instruments: pH, FOP and PQM, pH was best in predicting tenderness. Linear regression with tenderness as dependent variable and the on-line techniques as independent variables revealed the following R(2): 16, 8, 8 and 10% and SEE: 0.96, 1.01, 1.01 and 1.00 N for, respectively, pH1, FOP1, PQM1 and DDLT. Thus, the classical instruments and the DDLT technique, which is analogous to the CGM (Capteur Gras/Maigre), an officially accepted carcass grading apparatus in France and Belgium, are not good predictors of tenderness. PMID- 22063469 TI - Bacteriological comparison of parallel and counter flow water chilling of poultry meat. AB - Parallel flow water chilling and counter flow water chilling of young fattened broiler carcasses "Hybro" line were investigated. The samples were taken at 7 a.m. and 2 p.m. in March and April. The total count of aerobic mesophillic bacteria were determined at three stages of processing (evisceration, chilling using ether counter flow or parallel flow and final wash), and twice during the day (7 a.m. and 2 p.m.). Also, the total count of aerobic mesophilic bacteria was determined in samples of cold water (pre-chilling) and samples of ice water (chilling) at different times (7 a.m. and 2 p.m.). Significantly lower bacterial counts were obtained in carcasses treated with counter flow chilling. PMID- 22063470 TI - Uptake of gentamicin by vestibular efferent neurons and superior olivary complex after transtympanic administration in guinea pigs. AB - Transtympanic administration of gentamicin is a widely accepted and effective approach for treating patients with intractable vertigo. Previous studies have demonstrated the uptake, distribution and effects of gentamicin in peripheral vestibular and cochlear structures after transtympanic injection. However, little is known about whether transtympanically administered gentamicin is trafficked into more central auditory and vestibular structures and its effect on these structures. In this study, we used immunofluorescence to determine the distribution of gentamicin within the auditory and vestibular brainstem. We observed gentamicin immunolabeling bilaterally in the vestibular efferent neurons, and in the superior olivary complex, and ipsilaterally in the cochlear nucleus 24h after transtympanic administration of gentamicin, and that the drug could still be detected in these locations 30 days after injection. In contrast, no gentamicin labeling was detected in the vestibular nuclear complex. In the vestibular efferent neurons and superior olivary complex, gentamicin labeling was detected in the cytoplasm and cell processes, while in the cochlear nucleus gentamicin is mainly localized outside and adjacent to the cell bodies of neurons. Nerve fibers in cochlear nucleus, root of eighth nerve, as well as descending pathways from the superior olivary complex, are also immunolabeled with gentamicin continuously. Based on these data, we hypothesize that retrograde axonal transport of gentamicin is responsible for the distribution of gentamicin in these efferent nuclei including vestibular efferent neurons and superior olivary complex and anterograde axonal transport into the ipsilateral cochlear nucleus. PMID- 22063471 TI - Changes in inflammatory gene expression induced by hyperbaric oxygen treatment in human endothelial cells under chronic wound conditions. AB - Hyperbaric oxygen (HBO) therapy involves the inhalation of 100% oxygen, whilst inside a chamber at greater than atmospheric pressure. It is an effective treatment for chronic diabetic wounds, although the molecular mechanisms involved remain unclear. We hypothesised that HBO could alter inflammatory gene expression in human endothelial cells via a reactive oxygen/nitrogen species-mediated pathway. Endothelial cells were exposed to a chronic wound model comprising hypoxia (2% O(2) at 1 atmosphere absolute (ATA); PO(2) ~2 kPa) in the presence of lipopolysaccharide and TNF-alpha for 24h, then treated with HBO for 90 min (97.5% O(2) at 2.4 ATA; PO(2) ~237 kPa). 5h post-HBO, 19 genes involved in adhesion, angiogenesis, inflammation and oxidative stress were downregulated. Notably, only angiogenin gene expression, which promotes both angiogenesis and nitric oxide production (reflected by increased eNOS protein expression in this study), was upregulated. This led to a decrease in endothelial IL-8 mRNA and protein, which could help alleviate inflammatory processes during chronic wound healing. This was no longer evident 22.5h post-HBO, demonstrating the importance of daily exposures in HBO treatment protocols. These studies indicate that elevated oxygen transiently regulates inflammatory gene expression in endothelial cells, which may enhance chronic wound healing. PMID- 22063472 TI - A new generation of studies in RLS epidemiology. PMID- 22063473 TI - Incidence of restless legs syndrome in two population-based cohort studies in Germany. AB - OBJECTIVES: Prospective data about the new-onset of restless legs syndrome (RLS) are lacking. Our aim was to assess the incidence rate of RLS in the general population. METHODS: RLS, defined by the minimal diagnostic criteria, was assessed twice in two independently conducted prospective population-based cohort studies in Germany. The Dortmund Health Study (DHS) had a mean follow-up of 2.2 years, and included 1312 participants, and the Study of Health in Pomerania (SHIP) followed 4308 participants for, on average, 5.2 years. RLS was assessed during face-to-face interviews in both studies at baseline and at follow-up in SHIP, and with mailed questionnaires at follow-up in DHS. RESULTS: The age standardized incidence rate of RLS was 22/1000 person-years (p-y) (cumulative incidence over the follow-up: 9.1%) in DHS and 9/1000 p-y (cumulative incidence: 7.0%) in SHIP. Women had a higher incidence rate than men (DHS: 27/1000 p-y vs. 17/1000 p-y, p=0.28; SHIP: 12/1000 p-y vs. 7/1000 p-y, p<0.001). There was a linear increase in RLS incidence rate with age in both studies. The persistence of RLS symptoms from baseline to follow-up was 47.4% in DHS and 41.5% in SHIP. CONCLUSION: The incidence rate of RLS is high, while the persistence of RLS over time is low, suggesting that RLS symptoms vary considerably. The increased RLS incidence rate among women and the elderly is consistent with previous prevalence data. PMID- 22063474 TI - Disruption of individual nuo-genes leads to the formation of partially assembled NADH:ubiquinone oxidoreductase (complex I) in Escherichia coli. AB - The proton-pumping NADH:ubiquinone oxidoreductase, respiratory complex I, couples the electron transfer from NADH to ubiquinone with the translocation of protons across the membrane. In Escherichia coli the complex is made up of 13 different subunits encoded by the so-called nuo-genes. Mutants, in which each of the nuo genes was individually disrupted by the insertion of a resistance cartridge were unable to assemble a functional complex I. Each disruption resulted in the loss of complex I-mediated activity and the failure to extract a structurally intact complex. Thus, all nuo-genes are required either for the assembly or the stability of a functional E. coli complex I. The three subunits comprising the soluble NADH dehydrogenase fragment of the complex were detected in the cytoplasm of several nuo-mutants as one distinct band after BN-PAGE. It is discussed that the fully assembled NADH dehydrogenase fragment represents an assembly intermediate of the E. coli complex I. A partially assembled complex I bound to the membrane was detected in the nuoK and nuoL mutants, respectively. Overproduction of the DeltaNuoL variant resulted in the accumulation of two populations of a partially assembled complex in the cytoplasmic membranes. Both populations are devoid of NuoL. One population is enzymatically active, while the other is not. The inactive population is missing cluster N2 and is tightly associated with the inducible lysine decarboxylase. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. PMID- 22063475 TI - Robust decomposition of single-channel intramuscular EMG signals at low force levels. AB - This paper presents a density-based method to automatically decompose single channel intramuscular electromyogram (EMG) signals into their component motor unit action potential (MUAP) trains. In contrast to most previous decomposition methods, which require pre-setting and (or) tuning of multiple parameters, the proposed method takes advantage of the data-dependent strategies in the pattern recognition procedures. In this method, outliers (superpositions) are excluded prior to classification and MUAP templates are identified by an adaptive density based clustering procedure. MUAP trains are then identified by a novel density based classifier that incorporates MUAP shape and discharge time information. MUAP trains are merged by a fuzzy system that incorporates expert human knowledge. Finally, superimpositions are resolved to fill the gaps in the MUAP trains. The proposed decomposition algorithm has been experimentally tested on signals from low-force (<=30% maximal) isometric contractions of the vastus medialis obliquus, vastus lateralis, biceps femoris long-head and tibialis anterior muscles. Comparison with expert manual decomposition that had been verified using a rigorous statistical analysis showed that the algorithm identified 80% of the total 229 motor unit trains with an accuracy greater than 90%. The algorithm is robust and accurate, and therefore it is a promising new tool for decomposing single-channel multi-unit signals. PMID- 22063476 TI - Effects of sodium chloride, phosphate type and concentration, and pump rate on beef biceps femoris quality and sensory characteristics. AB - Beef biceps femoris muscles (n=45) were used to evaluate the effect of enhancement with solutions comprising 2.0% sodium chloride and either sodium hexametaphosphate (SHMP), sodium tripolyphosphate (STPP), or tetrasodium pyrophosphate (TSPP) at either 0.2% or 0.4% of product weight. All solutions were injected into muscle samples at either 112% (12% pump) or 118% (18% pump) of raw product weight. Muscles treated with all three phosphate types had decreased (P<0.05) free water compared to untreated muscles (CNT), and while TSPP-treated muscles were able to bind greater (P<0.05) additional water than CNT, STPP- and SHMP-treated muscles did not differ (P>0.05) from CNT. Disregarding phosphate type, steaks with 0.4% phosphate inclusion bound more (P<0.05) water than those with 0.2% phosphate inclusion. Steaks treated with STPP or TSPP had decreased (P<0.05) cooking losses than CNT, while SHMP-treated steaks did not differ (P>0.05) from CNT. Steaks injected at 18% pump had greater (P<0.05) percent moisture, and did not differ (P>0.05) in free water, water binding, or cooking losses from steaks injected at 12% pump. Although there were no differences (P>0.05) in Warner-Bratzler shear force in this study, steaks with SHMP, STPP, and TSPP all were rated more tender, and juicier (P<0.05) by sensory panelists than CNT steaks or steaks enhanced only with sodium chloride. Regardless of phosphate type, steaks enhanced with 0.4% phosphate and those steaks at 18% pump received improved (P<0.05) sensory tenderness ratings compared to 0.2% phosphate and 12% pump, respectively. These results suggest that enhancing biceps femoris muscles with STPP or TSPP can improve water retention, yield, and palatability characteristics. Additionally, enhancement with a phosphate/salt solution at an 18% pump rate, compared to a 12% pump rate, can allow for improved sensory tenderness perceptions without decreasing product yields. PMID- 22063477 TI - Effects of pre-harvest supplemental chlorate on beef carcass and meat quality. AB - Effects of feeding sodium chlorate on carcass quality, tenderness and color stability were evaluated. Heifers (n=64) were fed chlorate at either 0.01% or 0.05% of body weight (BW) in the last feeding or 0.01% for the last 5d before harvest, while control cattle received no chlorate. During the 12h period between feed withdrawal and transport to the harvest facility, the cattle were provided water containing either no sodium chlorate or sodium chlorate (approximately 30mM). Feed treatments at 0.01% of BW produced higher marbling scores than feeding 0.01% of BW for 5d. However, neither of these treatments produced marbling scores that were different from non-treated controls. Water supplementation increased tenderness in cattle fed 0.01% of BW for 5d, but decreased tenderness in cattle fed 0.05% of BW at the last feeding. Although tenderness differences existed, it is not clear whether or not they were caused by the feed or water treatments or by pre-existing variation in the cattle. Neither feed nor water supplementation affected color stability. These data suggest that chlorate preparations could be used to reduce pathogens without adversely impacting meat quality or display life. However, further research is needed to further substantiate these findings. PMID- 22063478 TI - Changes in sensory properties of Galician chorizo sausage preserved by freezing, oil-immersion and vacuum-packing. AB - Galician chorizo sausage, a dry-cured meat product from northwest Spain, was conserved by different methods with the aim of increasing its useful life. We studied changes in the sensory properties of this dry-cured meat product conserved by freezing, vacuum-packing and a traditional method involving immersion in sunflower oil. The reasons for the elimination of the samples conserved in sunflower oil at sampling 13 (week 23) was an increase in rancid flavor, acid flavor and external odor intensity. In sampling 18 (week 41) the samples conserved by vacuum-packing were eliminated because of increases in acid flavor, external and internal odor intensity, flavor intensity and after-taste persistence. In the frozen sausages the changes in sensory properties happened very slowly during storage. PMID- 22063479 TI - The relationship between body dimensions of living pigs and their carcass composition. AB - The performance of a visual image analysis (VIA) system was tested with regards to its potential to determine in vivo carcass composition and conformation, either alone, or in conjunction with other in vivo measures such as live weight and backfat depth. Pigs of both sexes of a commercial type were reared and slaughtered at weights ranging from 50 to 120 kg. Feeding was ad libitum on diets ranging from 0.14 to 0.19 kgkg(-1) crude protein content to produce animals of a range of body condition. Two analyses were carried out: the first analysis addressed the relationship between dimensionless carcass and VIA indices; the second analysis assessed the relationship between carcass composition and VIA body shape using detrended carcass and VIA data, which were produced by removal of allometric growth trends. A statistically significant relationship (P<0.05) between in vivo VIA body size and shape and carcass muscle dimensions and composition was found for most body regions. Adjusted R(2) statistics ranged between 0.13 and 0.54 for relative fat weights and between 0.14 and 0.51 for relative lean weights. The predictive power of the regression models, indicated by R(2)-like statistics for prediction, was approximately 70% of the adjusted R(2) values. The descriptive and predictive powers of the corresponding models generally strengthened if VIA indices were combined with other in vivo measurements. The relationships between in vivo and carcass measures remained statistically significant (P<0.05) after removal of the growth trends, although adjusted R(2) statistics generally decreased. The predictive power of models corresponding to the detrended measures was, however, weak. The results show in vivo VIA measurements to be useful in the estimation of muscle size, carcass conformation and composition, all of which are of significant importance to the pig production, marketing and processing industries. PMID- 22063480 TI - Identification and characterisation of halotolerant bacteria in spoiled dry-cured hams. AB - Twenty bacterial strains isolated from Italian dry-cured hams affected by the so called 'vein defect', were Gram positive, catalase and oxidase negative non-spore forming rods. Twelve strains were identified by molecular characterisation as Marinilactibacillus psychrotolerans. These strains were demonstrated to survive at high salt concentrations (up to 25% w/w, with growth up to 12% w/w), low temperatures (0-3 degrees C) and a pH range (6-7), which is encountered within the leg arterial vein. If strains of Marinilactibacillus are confirmed as causative agents of the 'vein defect', new manufacturing guidelines can be addressed to ham producers. PMID- 22063481 TI - Outdoor rearing of cull sows: Effects on carcass, tissue composition and meat quality. AB - The objective of this study was to provide some information on the influence of outdoor rearing on pasture (O) compared with indoor (I) on carcass and meat quality of cull sows. Twelve sows (6 per group) originating from the same breeding unit were slaughtered 11days after their last weaning. O sows had heavier and fatter carcasses, however lipid content in Longissimus (L) and Triceps brachii (TB) muscles was not affected. Grazing of O sows led to a high increase in the n-3 fatty acid content, particularly the C18:3 linolenic acid in the backfat and L muscle, thus improving the meat nutritional quality. Vitamin E content appeared (P=0.13) to be increased in the backfat of O sows, but not in the muscles. Lipid oxidation in meat during storage was similar between groups. Histological and metabolic observations showed that outdoor rearing increased the glycolytic capacity of the L muscle, and the oxidative capacity of the TB. Outdoor rearing did not influence meat pH1 and pHu, but decreased colour (a(*) and b(*) values) of the TB, and increased the processing yield of loin into cured bacon. Outdoor rearing decreased the red colour intensity and homogeneity, but improved tenderness of cured loins. PMID- 22063482 TI - Use of biodegradable films for fresh cut beef steaks packaging. AB - A comparative study on the use of biodegradable films for fresh cut meat packaging is presented. Beef steaks were packaged using three different films: polyvinyl chloride (PVC), which is actually used to package this food product, a biodegradable polymeric film composed of starch and polyester and a biodegradable film composed of a mixture of three biodegradable polyesters. The packaged beef steaks were stored at 4 and 15 degrees C to simulate actual storage conditions and thermal abuse, respectively. Colour, total viable counts as well as spoilage microorganism counts were monitored over a period of 6 days. No substantial differences were observed among the beef steaks packaged using the three investigated films, suggesting that biodegradable films, such as those used in this investigation, could be advantageously used to replace PVC films in packaging of fresh processed meat, reducing in this way the environmental impact of polymeric films. PMID- 22063483 TI - Biochemical and transcriptomic analyses of two bovine skeletal muscles in Charolais bulls divergently selected for muscle growth. AB - This work aimed to investigate the consequences of muscle growth selection on muscle characteristics. An oxidative muscle (Rectus abdominis, RA) and a glycolytic one (Semitendinosus, ST) were studied in two groups of six extreme young Charolais bulls of high or low muscle growth. Mitochondrial activity was lower in muscles of bulls with high muscle growth. Transcriptomic studies allowed the identification of putatively differentially expressed genes. The differential expression between genetic types of two genes in RA (a heat shock protein and a thyroid receptor interacting protein) and of seven genes in ST (including LEU5, tropomyosin 2, and sarcosin) was confirmed by different statistical approaches or Northern blot analysis, as well as the differential expression of five genes (including PSMD4 and DPM synthase) between RA and ST. Both biochemical and transcriptomic results indicate that selection on muscle growth potential is associated with reduced slow-oxidative muscle characteristics. Further studies are required to understand the physiological importance of genes whose expression is changed by selection. PMID- 22063484 TI - The effects of quality grade, aging, and location within muscle on Warner Bratzler shear force in beef muscles of locomotion. AB - Aging patterns of nine muscles from the chuck and round from two quality classifications of beef: USDA Select and upper 2/3 of USDA Choice grade were determined. The following muscles were evaluated: infraspinatus, triceps brachii lateral head, triceps brachii - long head, serratus ventralis, complexus, splenius, rhomboideus, vastus lateralis and rectus femoris. Muscles were divided into four portions, progressing from anterior to posterior or dorsal to ventral orientation to the carcass depending on muscle fiber orientation. One steak was removed from each portion and aged for 7, 14, 21, or 28 d postmortem, then Warner Bratzler shear force (WBSF) analysis was conducted. Consistent aging recommendations can be given for all muscles studied, as there was no aging by muscle interaction. An aging by USDA grade interaction was noted (P<0.05). The upper 2/3 of USDA Choice need not be aged beyond 7 d. USDA Select should be aged at least 14 d. Steak location within muscle had an effect (P<0.05) on WBSF values in four muscles. These data indicate that fabrication and merchandizing decisions should be made on an individual muscle basis. PMID- 22063485 TI - Effect of dietary conjugated linoleic acid (CLA) supplementation on CLA isomers content and fatty acid composition of dry-cured Parma ham. AB - To evaluate the effects of dietary conjugated linoleic acid (CLA) supplementation on cis-9, trans-11 and trans-10, cis-12 isomer content and on the fatty acid composition of subcutaneous adipose tissue and intramuscular lipids of biceps femoris, the lipids of 24 dry cured Parma hams, obtained from Large White pigs fed isoenergetic diets supplemented with either 0 (CON) or 0.25% (T1) CLA from 97 to 172kg live weight, were analysed by Ag(+)-HPLC and capillary GLC. The dietary treatment had no influence on lipid content of BF and subcutaneous adipose tissue but increased (P<0.01) the content of both isomers, more markedly in the latter tissue. CLA supplementation increased (P<0.01) myristic, palmitic, palmitoleic and total saturated fatty acids, and decreased oleic and eicosenoic acids in both tissues. In adipose tissue, an increase (P<0.05) in stearic acid content was observed. Supplementing the finishing diet of heavy pigs with CLA has thus shown to be an effective tool for increasing the CLA content in cured ham and, also, the saturated:unsaturated ratio of the lipids, a positive effect from a technological point of view. From a human nutritional standpoint, the changes occurring in fatty acid composition negatively affect the atherogenic and thrombogenic indexes, but probably these changes are of no particular concern, as they would only partly offset the progressive increase in the degree of unsaturation of heavy pig lipids that has occurred in recent years, as a consequence of reduced adipose depots in carcasses. PMID- 22063486 TI - Influence of pH on rheological properties of porcine myofibrillar protein during heat induced gelation. AB - Texture of meat products is dependent on the gelation characteristics of myofibrillar protein. Gaining an understanding of the gelation mechanism of meat gel systems is beneficial for the development of processed meat products as well as maintaining quality in meat products. The aim of this study was to investigate the impact of pH (5.6, 6.0, 6.5, and 7.0) on heat-induced gelation properties of myofibrillar proteins from porcine semimembranosus muscle. Dynamic rheological measurements were taken as the temperature increased by 1 degrees C/min from 20 to 85 degrees C, followed by a holding phase at 85 degrees C for 3min to ensure complete gelation and during a subsequent cooling where the temperature dropped from 85 to 5 degrees C at a rate of 5 degrees C/min. Storage modulus (G') increased as gel formation occurred, but decreased after reaching the temperature of myosin denaturation (52 degrees C) until approximately 60 degrees C when the gel strength increased again. This resulted in a peak and subsequent depression in the data. This depression in the curve was more pronounced with increasing pH. Results indicate protein denaturation and gel formation are pH dependent. Furthermore, rate of gelation appears to influence water-holding capacity. PMID- 22063487 TI - Effect of feed rationing during post-weaning growth on meat quality, muscle energy metabolism and fibre properties of Biceps femoris muscle in the rabbit. AB - During the weaning period (5 weeks of age), 50 hybrid rabbits were divided at random into five groups (or blocks). Animals from the block 1 were immediately slaughtered at this age and used as initial reference. The remaining rabbits were placed in individual cages and fed the same amount of food until slaughter, but differently rationed. From 5 to 8 weeks of age, the rabbits coming from blocks 2 and 4, and from blocks 3 and 5 received 70% and 90% of the ad libitum ration, respectively. Animals of blocks 2 and 3 were slaughtered at 8 weeks of age. Between 8 and 11 weeks of age, animals from blocks 4 and 5 were fed, respectively, 90% and 70% of the ad libitum ration, prior to sacrifice. At slaughter the Biceps femoris (BF) muscles were immediately removed from each rabbit and the ultimate pH (pHu) and meat colour L*a*b* parameters were measured. Thereafter, one BF was used for aldolase and isocitrate dehydrogenase (ICDH) activity determinations, while the other BF muscle was used for fibre distribution (% of betaR, alphaR and alphaW) and morphometric trait measurements. As expected, at 8 weeks of age, rabbits given for 3 weeks the strictest feed rationing (70% of the ad libitum ration) were lighter than rabbits fed the lowest feed rationing (90% of the ad libitum ration). At 11 weeks of age, rabbits given the 70% ration initially and then switched to 90% ration showed significantly higher body weights than rabbits fed the alternative diet (90% ration initially and then switched to 70% ration), and the best feed conversion ratio. Fibre type distribution, fibre cross-sectional area and compactness, colour and metabolic characteristics varied according to slaughter age. The effects of feeding treatment were low. PMID- 22063488 TI - Effects of restricted feeding and antioxidant supplementation on pig performance and quality characteristics of longissimus dorsi muscle from Landrace and Duroc pigs. AB - The present study was designed to evaluate the effects of compensatory growth diets with or without antioxidant inclusion (alpha-tocopheryl acetate (TA) or green tea catechins (GTC)) on pig performance and quality characteristics of longissimuss dorsi (LD) muscle from Landrace or Duroc pigs. Breed did not influence pig performance but had a significant effect on pork quality. Duroc muscle had higher intramuscular fat, ash and monounsaturated fatty acid levels and lower levels of moisture compared to Landrace. Lipid and pigment oxidation levels were higher in meat from Landrace pigs at initial stages of the study. Pigs fed restricted diets had reduced growth rates and lower back fat thickness. Decreasing the duration of energy restriction or significantly increasing dietary energy prior to slaughter resulted in compensatory growth. Supplementing diets with alpha-TA increased alpha-tocopherol levels in m. LD. Lipid oxidation levels (TBARS values) remained low throughout refrigerated storage. Dietary treatments did not affect colour stability or compositional analysis. Overall, lipid oxidation was highest in meat from pigs fed diets with greatest energy restriction and lowest in meat from pigs fed diets supplemented with alpha-TA or GTC. PMID- 22063489 TI - Prediction of carcass composition by impedance spectroscopy in lambs of similar weight. AB - Previous research on impedance measurements for the prediction of carcass composition was predominantly carried out on animals that varied widely in body weight, breed, or sex. The high accuracy for the estimated lean or fat mass was mainly obtained by including the body weight in the regression equations. The objective of this study was the prediction of carcass composition in lambs of similar weight. We used 70 male German Merino Mutton lambs and 70 male German Blackheaded Mutton lambs with 35 and 45kg live weight each. Impedance measurements with different electrode placements were carried out in vivo and on carcasses 20min and 24h postmortem. The carcass composition was ascertained by dissection of the left carcass side into lean, fat, and bone. R(2)-values for prediction of lean mass by impedance and body weight ranged between 0.11 and 0.71 within breeds and weight groups and between 0.84 and 0.89in the total material. Lean percentage was estimated with R(2)=0.18-0.48 within breeds and weight groups. The corresponding values for the total material varied from 0.23 to 0.37. We conclude that the impedance method is not suitable for the prediction of lean or fat percentage, neither in lambs of similar weight nor in heterogeneous animals. PMID- 22063490 TI - Development of an autonomous, wireless pH and temperature sensing system for monitoring pig meat quality. AB - This paper focuses on the development of a unique wireless pH and temperature monitoring system to assess pig meat quality. Pale, soft and exudative (PSE) pig meat continues to be a major problem in the pig meat industry today. The PSE condition in pork is related to a number of factors including genetics, pre slaughter stress and insufficient chilling of pig carcasses, which cause a rapid rate of glycolysis post-mortem (<1h). As a result the pH drops to low levels while the muscle temperature is still high. A wireless dual channel system that monitors pH and temperature simultaneously has been developed to provide pH and temperature data of the carcass during the first 24h after slaughter. We have demonstrated that this approach can distinguish in real time, pH and temperature profiles that are 'non-normal', and identify carcasses that are PSE positive quickly and easily. PMID- 22063491 TI - Evaluation of microsatellites as a potential tool for product tracing of ground beef mixtures. AB - Microsatellite genotyping was evaluated as a potential tool for DNA-based tracing of ground beef product. DNA from mixtures containing different numbers of individuals was analysed with a set of cattle microsatellite markers frequently used for parentage testing. As samples contained DNA from several animals, the microsatellite markers showed multiple peaks. The method could distinguish between mixtures containing equal amounts of meat from three different individuals, meat from three individuals mixed in different proportions, ground beef mixtures purchased in different cities, and different batches of ground beef patties. Limitations occurred when batches contained large numbers of individuals (>10) and different batches used meat from the same individuals. We conclude that DNA microsatellites may be useful for DNA traceability of ground beef mixtures prepared from less than 10 individuals, but where larger numbers of animals contribute to a mixture the method is not consistently accurate. PMID- 22063492 TI - Factors influencing tenderness in steaks from Brahman cattle. AB - The objective of this study was to identify a set of explanatory variables for Warner-Bratzler shear force and myofibril fragmentation indices after 7, 14, and 21d of aging; and sensory tenderness after 14d of aging of steaks from Brahman cattle. Insoluble collagen was negatively associated (P<0.001) with all tenderness traits across aging periods, and regression coefficients ranged from 5.69+/-0.49 to 9.12+/-0.29N for Warner-Bratzler shear force. The effect of lean color score (P<0.05) in analyses of unadjusted traits was diminished when data were adjusted for contemporary group (calves of the same sex, fed in one pen, and slaughtered the same day). Insoluble collagen may be of special importance and offer a unique opportunity to improve palatability of steaks from purebred Brahman cattle. PMID- 22063493 TI - Prediction of texture and colour of dry-cured ham by visible and near infrared spectroscopy using a fiber optic probe. AB - The potential of visible and near infrared spectroscopy to predict texture and colour of dry-cured ham samples was investigated. Sensory evaluation was performed on 117 boned and cross-sectioned dry-cured ham samples. Slices of approximate thickness 4cm were cut, vacuum-packaged and kept under frozen storage until spectral analysis. Then, Biceps femoris muscle from the thawed slices was taken and scanned (400-2200nm) using a fiber optic probe. The exploratory analysis using principal component analysis shows that there are two ham groups according to the appearance or not of defects. Then, a K nearest neighbours was used to classify dry-cured hams into defective or no defective classes. The overall accuracy of the classification as a function of pastiness was 88.5%; meanwhile, according to colour was 79.7%. Partial least squares regression was used to formulate prediction equations for pastiness and colour. The correlation coefficients of calibration and cross-validation were 0.97 and 0.86 for optimal equation predicting pastiness, and 0.82 and 0.69 for optimal equation predicting colour. The standard error of cross-validation for predicting pastiness and colour is between 1 and 2 times the standard deviation of the reference method (the error involved in the sensory evaluation by the experts). The magnitude of this error demonstrates the good precision of the methods for predicting pastiness and colour. Furthermore, the samples were classified into defective or no defective classes, with a correct classification of 94.2% according to pasty texture evaluation and 75.7% as regard to colour evaluation. PMID- 22063494 TI - Meat bolus properties in relation with meat texture and chewing context. AB - During chewing the meat sample is fragmented by compressive and shear bite forces while saliva is incorporated. At the end of this process meat is transformed into a bolus with specific properties, which elicit deglutition. This study aims to analyze the mechanical properties of the boli and juice-saliva interactions in different chewing contexts. Two groups of subjects with different chewing efficiencies participated in the study: healthy dentate (n=9) and denture wearers (n=7). Meat boli were obtained from two beef samples exhibiting different textures obtained by varying aging time and cooking temperature. Variables linked to saliva-food matrix interactions (boli volume and weight, dry matter content) were not dependent on muscle fiber disorganization evaluated using shear tests. No texture effect was observed from the mechanical properties of the boli, whatever the chewing context. Denture wearers swallowed less disorganized boli but with a similar water content as dentate. Between subjects variability was the highest for saliva-food interactions and the lowest for mechanical properties. The variations obtained in meat boli characteristics could have consequences on sensory properties perception and on the digestion process. PMID- 22063495 TI - The influences of carcass weight and depot on the fatty acid composition of fats of suckling Manchego lambs. AB - The effects of carcass weight (<5.5 kg, 5.5-6.5 kg, ?6.5 kg) of Manchego suckling lambs, type of fat depot of the leg (subcutaneous, intermuscular and intramuscular) and muscle (m. longissimus dorsi (LD) or m. quadriceps femoris (QF)) on the fatty acid composition were studied. Carcass fatness increased with increasing carcass weight. However, few differences in fatty acid proportion were observed between the three carcass weight groups. The lightest carcasses had lower proportions of myristic (C14:0) and palmitoleic (C16:1) acid and higher proportions of stearic (C18:0) acid, desirable fatty acids (DFA) (C18:0+total unsaturated fatty acid (TUFA)) and a greater nutritive value ((C18:0+C18:1)/C16:0). The fatty acid composition of subcutaneous and intermuscular fat depots of the leg were similar, whereas the intramuscular fat depot was different from both of these, since it had a lower proportion of saturated fatty acids (SFA), a greater proportion of TUFA, higher PUFA/SFA and n 6/n-3 ratios, and greater DFA and nutritive values. The intramuscular fat of the LD was more saturated than QF, higher SFA, and had lower value of PUFA/SFA ratio and DFA. These results indicated that the intramuscular fat quality of the leg was better than subcutaneous and intermuscular fat depots and also that intramuscular fat displayed better attributes of quality (lower SFA, higher TUFA, and greater PUFA/SFA ratio and DFA as well) than intramuscular fat of the LD from the consumer health standpoint. Despite carcass weight affected carcass fatness, it did not seem to influence the proportions of saturated or polyunsaturated fatty acids. For this reason, carcass weight probably had little effect on the organoleptic characteristics of the meat. PMID- 22063496 TI - Time-related changes in cathepsin B and L activities during processing of Jinhua ham as a function of pH, salt and temperature. AB - Sixty experimental Jinhua hams were processed by traditional methods using green hams from local crossbred pigs of Lanxi, Zhejiang province, PR China. Biceps femoris was sampled from five hams randomly taken after each processing stage. Potential activities of cathepsin B and L were determined. The effects of temperature, salt content, pH value and nitrate content on the activities of cathepsin B and L were evaluated using response surface methodology (RSM) and the actual activities of cathepsin B and L during Jinhua ham processing were calculated. The results showed that potential activities of cathepsin B and L decreased gradually from 11332.05 to 9955.50 Ug(-1) prior salting to 1055.32 1359.90 Ug(-1) at the end of post-aging, respectively. After processing, about 9.31% original potential activity of cathepsin B and 13.66% original potential activity of cathepsin L were left. Temperature, pH value and salt content showed significant effects on cathepsin B and L activities. By stepwise regression analysis, two quadratic regression equation models were built individually for estimating cathepsin B and L activities. The models predicted that the actual activities of cathepsin B and L were less than 5% of their corresponding potential activities most of the time before half of loft-aging and about 15% and 20% during the rest processing periods. Nevertheless, cathepsin B and L retained actual activities throughout processing, especially during loft-aging and post aging periods. PMID- 22063497 TI - Development of the aerobic spoilage flora of chilled rabbit meat. AB - Even though worldwide production of rabbit meat is over 1,000,000ton, little information is available on rabbit meat microbiology. This paper reports on the microflora developing on chill-stored rabbit carcasses. Four different lots of 24h post-mortem rabbit carcasses dressed and kept at 0 degrees C in a medium-size abattoir were collected and evaluated for sensory, physicochemical and microbiological changes during aerobic storage at 3+/-1 degrees C. Mean initial pH value (pH(24)), extract-release volume (ERV) and lactate content of Biceps femoris muscle, were 6.26+/-0.20, 13.50+/-3.50ml and 0.70+/-0.07%, respectively. As with other muscle foods kept chilled in air, pH increased and ERV and lactate decreased as storage progressed. Initial levels (logcfu/g) of aerobes (APC), psychrotrophic flora, Pseudomonas spp., Brochothrix thermosphacta, lactic acid bacteria, Enterobacteriaceae and yeasts were 4.76+/-0.31, 4.81+/-0.81, 3.39+/ 1.12, 2.01+/-0.92, 2.76+/-0.51, 0.49+/-0.45 and 3.46+/-0.32, respectively. Pseudomonads, most of them fluorescent, and to a lesser extent B. thermosphacta and yeasts grew faster than the remaining microorganisms and became predominant at the end of the shelf life. Carcasses spoiled when mean APC, psychrotrophic and pseudomonads numbers were ca. 8logcfu/g, their mean shelf life being estimated at 6.8 days. A lot of DFD-like rabbit carcasses, with higher pH and lower ERV values but similar microbial loads to normal meat, developed a strong putrid odour after 4 days. PMID- 22063498 TI - A real time PCR (RT-PCR) alternative assay to detect the T/C mutation in position 1843 of the ryanodine receptor gene. AB - The discovery of the causal mutation of malignant hyperthermia in pigs, a T for C substitution in base 1843 of the ryanodine receptor gene, opened the door to selection procedures based on the analysis of ryanodine receptor genotype based on PCR amplification of the region containing base 1843, subsequent digestion with specific restriction enzymes of the amplified DNA fragment, and electrophoretic analysis of the resulting bands. In this paper, we describe an assay that allows analysis of the three possible genotypes of the ryanodine receptor gene using real time PCR to amplify and detect them in a single step. Results obtained with the RT-PCR assay described in this work match 100% with those obtained using traditional PCR methods. RT-PCR methods are cheaper and faster than traditional ones allowing one to genotype up to 384 samples in a single run. PMID- 22063499 TI - Evaluation method for firmness and stickiness of porcine perirenal fat. AB - The firmness and stickiness of chilled porcine fat at 4 degrees C were evaluated with an Instron compression tester and compared with fatty acid composition. Firmness of cylindrical adipose samples was measured at a force producing a 70% deformation. Firmness values were correlated with refractive index data (r= 0.67), melting point data (r=0.77), and saturated fatty acids concentration data (r=0.72) of the extracted lipid, and with sensory scores data (r=0.89). The firmness value correlated with the concentration of C18:0 (r=0.73). The stickiness of comminuted fat samples was evaluated with the Instron using a fixed load at a compression force of 20N and crosshead speed of 1.5mm/s. Single regression analyses showed that the stickiness parameters, stretch and adhesiveness correlated negatively with the concentration of the saturated fatty acids data (r=-0.64, -0.52) but positively and weakly with the monounsaturated fatty acids data (r=0.28, 0.34). Multiple regression analysis improved their relationships. These results indicate that mechanical evaluation may be used to predict porcine fat texture and saturated fatty acids concentration. PMID- 22063500 TI - Susceptibility profiles and resistance genes for carbapenems (cfiA) and metronidazole (nim) among Bacteroides species in a Turkish University Hospital. AB - Sixty-six nonduplicate Bacteroides clinical isolates collected at Marmara University Hospital were tested to investigate carbapenem and metronidazole resistance profiles and to detect the resistance genes (cfiA and nim) and related insertion sequence (IS) elements. The study found that there were no strains resistant to metronidazole and nim genes were not detected in any of the strains. Five Bacteroides fragilis strains were resistant to meropenem, one of which was also resistant to imipenem. The cfiA gene was detected in 27% of strains, 32% of strains had the IS1187 element, and five strains harbored both gene cfiA and IS1187. These results indicate higher rates of carriage of the cfiA gene and IS1187 insertion elements than have been reported in other countries. PMID- 22063501 TI - Structural studies of the exopolysaccharide consisting of a nonasaccharide repeating unit isolated from Lactobacillus rhamnosus KL37B. AB - A novel structure of exopolysaccharide from the lactic acid bacteria (LAB) Lactobacillus rhamnosus KL37B, from the human intestinal flora, is described. During the structural investigation of the exopolysaccharide it was found that the repeating unit is a nonasaccharide, which is the largest repeating unit found in LAB exopolysaccharides to date. The polysaccharide material was prepared by TCA extraction of a bacterial cell mass, purified by anion-exchange and gel permeation chromatography and characterized using chemical and enzymatic methods. On the basis of monosaccharide and methylation analysis and also 1D and 2D (1)H and (13)C NMR spectroscopy the exopolysaccharide was shown to be composed of the following nonasaccharide repeating unit: The physicochemical cell surface study and adhesive properties indicated distinct surface properties of Lactobacillus rhamnosus strain KL37B with high adhesive abilities to Caco-2 cells, hydrophobicity and slime production, in comparison to other Lactobacillus strains used as controls. PMID- 22063502 TI - Molecular dynamics simulation of the dissolution process of a cellulose triacetate-II nano-sized crystal in DMSO. AB - An understanding of the dissolution process of cellulose derivatives is important not only for basic research but also for industrial purposes. We investigated the dissolution process of cellulose triacetate II (CTA II) nano-sized crystal in DMSO solvent using molecular dynamics simulations. The nano-sized crystal consists of 18 CTA chains. During the 9 ns simulation, it was observed that one chain (C01) located at the corner of the lozenge crystal was solvated by the DMSO molecules and moved away from the remaining cluster into the DMSO solvent. The analysis showed that the breakage of the interaction between the H1, H3, and H5 hydrogens of the pyranose ring and the acetyl carbonyl oxygen in the C01 and C02 adjacent chains would be crucial for the dissolution of CTA. The DMSO molecules solvating around these atoms would prevent the re-crystallization of the CTA molecules and facilitate further dissolution. PMID- 22063503 TI - Computational study of mutarotation in erythrose and threose. AB - For the first time the mutarotation mechanism of furanose rings has been investigated, with and without solvent. The transformations from open-chain furanose to D-erythrose and D-threose have been studied at B3LYP/6-311++G(d,p) and G3MP2B3 levels, in vacuum and in solution through continuum solvation models. We studied the catalytic influence of one, two or three water molecules, as well as simplified models of carbohydrates, that is, methanol and 1,2-ethanediol. Water molecules significantly reduce the energy barrier of the hemiacetal formation occurring between the open-chain and furanose configurations. The energy barrier is optimally reduced by two water molecules. Methanol yields a smaller transition state barrier than the one obtained with a single water molecule. In contrast, 1,2-ethanediol does not provide a lower transition state compared to the barrier in the presence of two water molecules. PMID- 22063504 TI - Controversial behavior of aminoguanidine in the presence of either reducing sugars or soluble glycated bovine serum albumin. AB - The elucidation of the controversial inhibitory effect of aminoguanidine (AG) on the cross-linking and fluorescent advanced glycation end products (AGEs) formation during long-term in vitro glycation of type I collagen with 250 mM reducing sugars or 0.5mg/ml soluble glycated bovine serum albumin (AGE-BSA) was researched. Chromatographic and SDS-PAGE analyses revealed the formation of aggregates during collagen glycation. AG at all concentrations (5-80 mM) prevented the cross-linking of collagen peptides with monosaccharides but an increase in fluorescence with a maximum value at 10 mM AG was noticed. In the presence of AGE-BSA, AG prevented the cross-linking process and decreased the fluorescence levels in a concentration-dependent manner. Our results suggest that AG is an efficient inhibitor of collagen cross-linking and the highest increase in fluorescence due to reducing sugars and AG can be explained by the competition between guanidine group of AG and arginine residues of some protein-bound dideoxyosones, which could form fluorescent compounds. PMID- 22063505 TI - Maria Sklodowska-Curie, analytical chemist. PMID- 22063506 TI - 2011--the year of Maria Sklodowska-Curie: a woman for eternity, but a Polish woman of her time. PMID- 22063507 TI - Solventless and solvent-minimized sample preparation techniques for determining currently used pesticides in water samples: a review. AB - The intensification of agriculture means that increasing amounts of toxic organic and inorganic compounds are entering the environment. The pesticides generally applied nowadays are regarded as some of the most dangerous contaminants of the environment. Their presence in the environment, especially in water, is hazardous because they cause human beings to become more susceptible to disease. For these reasons, it is essential to monitor pesticide residues in the environment with the aid of all accessible analytical methods. The analysis of samples for the presence of pesticides is problematic, because of the laborious and time consuming operations involved in preparing samples for analysis, which themselves may be a source of additional contaminations and errors. To date, it has been standard practice to use large quantities of organic solvents in the sample preparation process; but as these solvents are themselves hazardous, solventless and solvent-minimized techniques are coming into use. This paper discusses the most commonly used over the last 15 years sample preparation techniques for monitoring organophosphorus and organonitrogen pesticides residue in water samples. Furthermore, a significant trend in sample preparation, in accordance with the principles of 'Green Chemistry' is the simplification, miniaturization and automation of analytical techniques. In view of this aspect, several novel techniques are being developed in order to reduce the analysis step, increase the sample throughput and to improve the quality and the sensitivity of analytical methods. The paper describes extraction techniques requiring the use of solvents liquid-liquid extraction (LLE) and its modifications, membrane extraction techniques, hollow fibre-protected two-phase solvent microextraction, liquid phase microextraction based on the solidification of a floating organic drop (LPME-SFO), solid-phase extraction (SPE) and single-drop microextraction (SDME) - as well as solvent-free techniques - solid phase microextraction (SPME) and stir bar sorptive extraction (SBSE). The advantages and drawbacks of these techniques are also discussed, and some solutions to their limitations are proposed. PMID- 22063508 TI - New trends in quantification of acrylamide in food products. AB - Methods applied in acrylamide quantification in foods have been reviewed in this paper. Novel analytical techniques like capillary electrophoresis (CE), immunoenzymatic test (ELISA) and electrochemical biosensors, which can replace traditional methods like high performance liquid chromatography (HPLC) and gas chromatography (GC) were presented. Short time of analysis and high resolution power of electrophoretic techniques caused that they became routinely used in food analysis apart from high performance liquid chromatography and gas chromatography. Application of modern chromatography methods like ultra performance liquid chromatography (UPLC) in acrylamide quantification considerably shortened the time of analysis and decreased the consumption of indispensable reagents. The most promising approaches to acrylamide quantification in foods are electrochemical biosensors and immunoenzymatic tests. In contrast to chromatography and electrophoretic methods they require neither expensive equipment nor time consuming sample preparation and allow for fast screening of numerous samples without the usage of sophisticated apparatuses. Because of many advantages such as miniaturization, rapid and simple analysis, and high sensitivity and selectivity, biosensors are thought to replace conventional methods of acrylamide quantification in food. PMID- 22063509 TI - Lipophilicity study of some non-steroidal anti-inflammatory agents and cephalosporin antibiotics: a review. AB - Lipophilicity properties have long been considered a vital component of drug discovery and development, providing insight into the role of molecular properties in the biological activity of known and new compounds. An extensive survey of the literature published in analytical and pharmaceutical chemistry journals has been conducted. Separation, optical, electrochemical and calculation methods which were developed and used for determination of lipophilicity non steroidal anti-inflammatory agents and cephalosporin antibiotics in drugs and biological materials, have been reviewed. This review covers over 100 miscellaneous methods. Presented review highlighted some recent developments and new techniques that have been used in the lipophilicity detection of two different kinds of drugs. PMID- 22063510 TI - Use of carbon nanotubes and electrothermal atomic absorption spectrometry for the speciation of very low amounts of arsenic and antimony in waters. AB - A procedure for the determination of inorganic arsenic (III, V) and antimony (III, V) in water samples by using a miniaturized solid-phase extraction with carbon nanotubes followed by electrothermal atomic absorption measurement is proposed. The trivalent species are first complexed with ammonium pyrrolidinedithiocarbamate, next retained in a mini-column containing nanotubes and then eluted by means of a plug of an ammonia solution. The atomizer is impregnated with a tungsten salt which acts as an effective chemical modifier during the heating cycle. Total inorganic arsenic and antimony are determined after the reduction of the pentavalent forms with an ammonium iodide solution. Pentavalent arsenic and antimony are calculated by difference. When using 50 mL sample solutions, the limits of detection are 0.02 and 0.05 MUg L(-1) for As and Sb, respectively, and the enrichment factor is 250. The relative standard deviations calculated for five determinations at the 1 MUg L(-1) level are below 4%. PMID- 22063511 TI - Synthesis of molecularly imprinted monolithic fibers for solid-phase microextraction of acetaldehyde from head-space of beverages stored in PET bottles. AB - Molecularly imprinted monolithic fibers were synthesized and evaluated for solid phase microextraction (SPME) of acetaldehyde from head-space of beverages stored in poly(ethylene terephthalate) (PET) bottles. The fibers were prepared by co polymerization of methacrylic acid and ethylene glycole diethacrylate as functional monomer and cross-linker, respectively. Acetaldehyde was used as template molecule during polymerization process, in order to leave specific cavities after leaching off from the co-polymer. Narrow bore (i.d. 100 MUm) glass capillaries as molds were filled with polymerization mixture containing cross linker, functional monomer, template molecule, initiator and porogen solvent. This mixture is then polymerized to form a continuous porous monolith that conforms to the shape of the mold. The resulting monolithic fibers were employed by a micro-syringe to extract acetaldehyde from head-space of sample solutions. Gas chromatography/mass spectrometry (GC/MS) was used to analyze adsorbed acetaldehyde to the fibers. Parameters influencing adsorption of acetaldehyde from head-space of standard solutions to the fiber and subsequently desorption in the GC chamber were optimized. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.01 and 0.03 MUg mL(-1), respectively. The intra-day and inter-day precisions of the peak areas for five replicates were 8 and 15%, respectively. PMID- 22063512 TI - Colorimetric-solid phase extraction method for trace level determination of arsenite in water. AB - This paper introduces a method for the determination of inorganic arsenite [As(III)] in water at low MUg L(-1) by a sorption-photometric method known as colorimetric-solid phase extraction (C-SPE). The method relies on the selective extraction and concentration of an analyte on a reagent-impregnated SPE membrane, followed by direct detection of the extracted colored complex by a handheld diffuse reflectance spectrophotometer (DRS) operating in the visible spectral region. The well-established chemistry of the classic redox titrimetric method for molecular iodine (I(2)) standardization by arsenious oxide (As(2)O(3)) serves as the basis for this analysis. I(2), which is added to the aqueous sample in an excess with respect to the analyte, serves as a colorimetric indicator. The arsenite-iodine reaction is rapid, allowing an exact volume of analyte solution to be immediately passed through an SPE membrane via a syringe after mixing with the indicator. An SPE membrane that is impregnated with the complexing agent poly(vinyl-pyrrolidone) (PVP) serves to complex and concentrate excess I(2) not consumed by the As(III) analyte. The amount of complexed I(2) is determined by a DRS reading directly on the membrane surface. The spectrophotometric measurement can be made in a few seconds, with a total sample workup and readout time of ~ 1 2 min. The limit of detection (LOD) for this determination is below 10 MUg L(-1). The potential effectiveness of the method for the analysis of spiked tap water and surface water is examined, and results from preliminary interference studies are described. The work herein also shows that by applying the principles of negligible depletion (ND), the analytical procedure could be simplified by eliminating the need to pass an exact volume of a sample through the impregnated membrane as long as it exceeds the predetermined minimum volume. PMID- 22063513 TI - Uncertainty of ozone measurements with the primary standard reference photometer (SRP45). AB - A comparison of the ozone primary reference standard photometer serial number 45 (SRP45) against the National Institute of Standards and Technology (NIST) instruments, serial number 0 (SRP0) and 2 (SRP2), has been performed in order to establish the traceability and comparability of ozone measurements made by the Chilean atmospheric science community. A complete uncertainty budget was developed for SRP45, using a GUM approach. The results of the comparisons allow us to conclude that SRP45, SRP0 and SRP2 are comparable according to international criteria over an ozone mole fraction range of 0 nmol mol(-1) to at least 500 nmol mol(-1). The official result for the validation of SRP45 is x(ozone)(SRP45)=[0.013+0.99806x(ozone)(SRP2)] nmol mol(-1) with an expanded uncertainty of [Formula in text] from 0 to 500 nmol mol(-1). PMID- 22063514 TI - A fast method using a new hydrophilic-lipophilic balanced sorbent in combination with ultra-high performance liquid chromatography for quantification of significant bioactive metabolites in wines. AB - This manuscript describes the development and validation of an ultra-fast, efficient, and high throughput analytical method based on ultra-high performance liquid chromatography (UHPLC) equipped with a photodiode array (PDA) detection system, for the simultaneous analysis of fifteen bioactive metabolites: gallic acid, protocatechuic acid, (-)-catechin, gentisic acid, (-)-epicatechin, syringic acid, p-coumaric acid, ferulic acid, m-coumaric acid, rutin, trans-resveratrol, myricetin, quercetin, cinnamic acid and kaempferol, in wines. A 50-mm column packed with 1.7-MUm particles operating at elevated pressure (UHPLC strategy) was selected to attain ultra-fast analysis and highly efficient separations. In order to reduce the complexity of wine extract and improve the recovery efficiency, a reverse-phase solid-phase extraction (SPE) procedure using as sorbent a new macroporous copolymer made from a balanced ratio of two monomers, the lipophilic divinylbenzene and the hydrophilic N-vinylpyrrolidone (OasisTM HLB), was performed prior to UHPLC-PDA analysis. The calibration curves of bioactive metabolites showed good linearity within the established range. Limits of detection (LOD) and quantification (LOQ) ranged from 0.006 MUg mL(-1) to 0.58 MUg mL(-1), and from 0.019 MUg mL(-1) to 1.94 MUg mL(-1), for gallic and gentisic acids, respectively. The average recoveries +/- SD for the three levels of concentration tested (n=9) in red and white wines were, respectively, 89 +/- 3% and 90 +/- 2%. The repeatability expressed as relative standard deviation (RSD) was below 10% for all the metabolites assayed. The validated method was then applied to red and white wines from different geographical origins (Azores, Canary and Madeira Islands). The most abundant component in the analysed red wines was (-)-epicatechin followed by (-)-catechin and rutin, whereas in white wines syringic and p-coumaric acids were found the major phenolic metabolites. The method was completely validated, providing a sensitive analysis for bioactive phenolic metabolites detection and showing satisfactory data for all the parameters tested. Moreover, was revealed as an ultra-fast approach allowing the separation of the fifteen bioactive metabolites investigated with high resolution power within 5 min. PMID- 22063515 TI - On the lability of dissolved Cu, Pb and Zn in freshwater: optimization and application to the Deule (France). AB - A procedure to determine lead and zinc by anodic stripping voltammetry and copper by cathodic stripping voltammetry in natural river samples was developed and validated. Cu determination involves the adsorption of Cu complexes with 8 hydroxyquinoline (oxine) onto a hanging mercury drop electrode. All samples were studied at natural pH and following optimal conditions were found: an accumulation step at -1.3 V (all potential values in the paper are given versus the Ag/AgCl, [KCl]=3M reference electrode) during 30s for determination of Zn contents and at -0.7 V during 60s for determination of Pb contents. Concerning Cu analysis, the optimal oxine concentration was found to be 10(-5)M with a deposition potential of -1.1 V during 30s followed by an adsorption step at -0.25 V during 15s. This procedure was afterwards validated by using certified reference freshwater and performing an intercalibration exercise. Finally the method was successfully applied in the Deule River, highly contaminated by dissolved Zn and to a lesser extent by Pb and Cu, due to past and present activities of metallurgical plants. Under these optimal conditions, metal concentrations measured by our voltammetric procedures in the Deule River were found in the range 12.4-23.2 nM for Zn, 1.7-3.2 nM for Pb and 4.9-7.6 nM for Cu. PMID- 22063516 TI - Determination of Pu and U isotopes in safeguard swipe sample with extraction chromatographic techniques. AB - A simple and reliable separation method of plutonium and uranium was developed using extraction chromatographic techniques. Using the separation method of plutonium and uranium developed in this study, recoveries of plutonium and uranium were compared with those by commercial separation methods of Pu and U. The redox reactions of hydrogen peroxide with plutonium in a nitric acid medium were investigated by UV-vis-NIR absorption spectroscopic techniques. The separation method of Pu and U isotopes with the UTEVA resin updated in this study could be effective to measure quantitatively nano- and picogram amounts of uranium and plutonium in swipe samples using isotope dilution thermal ionization mass spectrometry (ID-TIMS). PMID- 22063517 TI - An anionic exchange stir rod sorptive extraction based on monolithic material for the extraction of non-steroidal anti-inflammatory drugs in environmental aqueous samples. AB - In this study, a stir rod sorptive extraction (SRSE) adsorbent material was prepared by coating poly(4-vinylpyridine-co-ethylene glycol dimethacrylate) [poly(VP-co-EDMA)] monolithic polymer on stir rod, and then applied to the extraction of three non-steroidal anti-inflammatory drugs (NSAIDs) in environmental aqueous samples. The preparation conditions of monolithic material such as the amount of porogen and the ratio of functional monomer to cross-linker were investigated. To achieve the best extraction efficiency, several parameters, including pH value of sample solution, salt concentration in sample matrix, desorption solvent, extraction time, and desorption time, were optimized. By combining SRSE and high performance liquid chromatography with ultraviolet detector, a SRSE-HPLC/UV method for the determination of NSAIDs in environmental aqueous samples was proposed successfully. The limits of detection (LODs) of the developed method for three NSAIDs ranged between 0.09 and 0.25 ng/mL. Good method reproducibility presented as intra- and inter-day precisions were also obtained with the relative standard deviations (RSDs) less than 8.7% and 9.8%, respectively. PMID- 22063518 TI - Electromembrane extraction and HPLC analysis of haloacetic acids and aromatic acetic acids in wastewater. AB - For the first time, haloacetic acids and aromatic acetic acids were extracted from wastewater samples using electromembrane extraction (EME). A thin layer of toluene immobilized on the walls of a polypropylene membrane envelope served as an artificial supported liquid membrane (SLM). The haloacetic acids (HAAs) (chloroacetic acid, dichloroacetic acid, and trifluoroacetic acid) and aromatic acetic acids (phenylacetic acid and p-hydroxyphenylacetic acid) were extracted through the SLM and into an alkalized aqueous buffer solution. The buffer solution was located inside the membrane envelope. The electrical potential difference sustained over the membrane acted as the driving force for the transport of haloacetic acids into the membrane by electrokinetic migration. After extraction, the extracts were analyzed by high-performance liquid chromatography-ultraviolet detection. The detection limits were between 0.072 and 40.3 ng L(-1). The calibration plot linearity was in the range of 5 and 200 MUg L(-1) while the correlation coefficients for the analytes ranged from 0.9932 to 0.9967. Relative recoveries were in the range of 87-106%. The extraction efficiency was found to be comparable to that of solid-phase extraction. PMID- 22063519 TI - Microwave plasma torch-atomic emission spectrometry for the on-line determination of rare earth elements based on flow injection preconcentration by TiO2-graphene composite. AB - In this work, we synthesized TiO(2)-graphene composite as a novel preconcentration material. It was enclosed in a microcolumn in the on-line flow injection system to adsorb trace light (La), medium (Tb), and heavy (Ho) rare earth elements (REEs) prior to their determinations by microwave plasma torch atomic emission spectrometry (MPT-AES). Various experimental parameters, such as sample loading time, sample flow rate, sample pH, eluent flow rate, eluent concentration, and interfering ions, were investigated systematically. Under the optimum conditions, the detection limits (three times of standard deviations of blank by 7 reiterations) of La, Tb, and Ho were found to be 2.2, 1.6, and 2.8 MUg L(-1), with enrichment factors of 17.1, 11.1, and 10.2, respectively. Relative standard deviations for the determination of the target REEs were 3.6%, 1.3%, and 1.4%, respectively (n=7). The developed method was validated by the analysis of La, Tb, and Ho in certified reference material (GBW07313, marine sediment) and high purity REE oxide samples. PMID- 22063520 TI - Novel monohydrogenphosphate ion-selective polymeric membrane sensor based on phenyl urea substituted calix[4]arene. AB - A highly selective and sensitive PVC membrane, containing phenylurea substituted calix[4]arene was found to be a suitable ionophore for monohydrogen phosphate (HPO(4)(2-)) ions that exhibited a Nernstian response (with a slope of -29.4 +/- 0.3 mV decade(-1)). The working concentration range of the electrode was 6.0 * 10(-8)-1.0 * 10(-1) mol L(-1) with a detection limit of 2.0 * 10(-8) mol L(-1). The response time of the sensor in the whole concentration range is very short (<8s), with a considerable lifetime of at least 15 weeks. The sensor possesses the advantages of short response time, low detection limit and a high selectivity towards a large number of inorganic anions. The developed sensor was used as an indicator electrode in potentiometric titration of monohydrogen phosphate ion with barium chloride. The proposed sensor was successfully applied for the direct determination of monohydrogen phosphate in real life samples. PMID- 22063521 TI - An automated solid phase extraction coupled with electrothermal atomic absorption spectrometric determination of Pb(II) in high salt content samples. AB - A novel Pb(II) analysis in dialysis concentrates and seawater samples has been developed with on-line separation and preconcentration system coupled with electrothermal atomic absorption spectrometer (FI-ETAAS). Lewatit Monoplus TP207 imminodiacetat chelating resin was used for separation and preconcentration of Pb(II) ions at pH 4.0. The influence of the analytical parameters such as type of eluent, flow rate of eluent and sample, eluent volume and matrix ions were investigated. W-Rh coated furnace was used as the atomization site. A preconcentration factor of 14 and a detection limit (3s/b) of 12 ng L(-1), along with the sampling frequency of 21 h(-1) were achieved with a 170 s sample loading time and with 2.8 mL sample consumption. The relative standard deviation (RSD) was 1.6% for 1 MUg L(-1) Pb(II) level. The developed method was used for Pb(II) analysis in dialysis concentrates and seawater samples. The certified reference material (CRM403) experimental results are in good agreement with the certified value. PMID- 22063522 TI - Glucose detection with surface plasmon resonance spectroscopy and molecularly imprinted hydrogel coatings. AB - Molecularly imprinted hydrogel membranes were developed and evaluated for detection of small analytes via surface plasmon resonance spectroscopy. Imprinting of glucose phosphate barium salt into a poly(allylamine hydrochloride) network covalently bound to gold surfaces yielded a selective sensor for glucose. Optimization of relative amounts of chemicals used for preparation of the hydrogel was performed to obtain highest sensitivity. Addition of gold nanoparticles into the hydrogel matrix significantly amplified its response and sensitivity due to the impact of gold nanoparticles on the refractive index of the sensing layer. Evaluation of its selectivity showed that the sensor displayed preferential recognition to glucose compared to structurally related sugars in addition to being unaffected by phosphate as well as compounds containing amine groups, like creatinine. The detection limit of glucose in deionized water was calculated to be 0.02 mg/mL. The developed sensor was finally exposed to human urine spiked with glucose illustrating the coating's ability to re-bind the analyte in complex matrices. While the working concentration range in water was determined to be suitable for glucose monitoring in diabetic individuals at physiological levels, the detection in urine was determined to be 0.12 mg/mL. The decreased performance in urine provided an initial perspective on the difficulties associated with measurements in complex media. PMID- 22063523 TI - Automatic heating and cooling system in a gas purge microsyringe extraction. AB - The gas purge microsyringe extraction (GP-MSE) technique offers quantitative and simultaneous extraction, and rapid gas chromatographic-mass spectrometric determination of volatile and semivolatile chemicals is possible. To simplify the application, a new automatic temperature control system was developed here. Stable heating and cooling over a wide range of temperatures were achieved using a micro-heater and thermoelectric cooler under varying gas flow conditions. Temperatures could be accurately controlled in the range 20-350 degrees C (heating) and 20 to -4 degrees C (cooling). Temperature effects on the extraction performance of the GP-MSE were experimentally investigated by comparing the recoveries of polycyclic aromatic hydrocarbons (PAHs) under various experimental conditions. A sample treatment was completed within 3 min, which is much less than the time required for chromatographic analysis. The recovery of chemicals determined ranged from 81 to 96%. High reproducibility data (RSD <= 5%) were obtained for direct extraction of various analytes in spiked complex plant and biological samples. The data show that the heating and cooling system has potential applications in GP-MSE system for the direct determination of various kinds of volatile and semivolatile chemicals from complex matrices without any, or only minor, sample pretreatment. PMID- 22063524 TI - Development of a simple field test for vehicle exhaust to detect illicit use of dyed diesel fuel. AB - Tax-free diesel fuel is intended for off-road uses such as agricultural operations, but illicit use of this fuel does occur and is a convenient way of evading payment of excise taxes. Current enforcement to prevent this practice involves visual inspection for the red azo dye added to the fuel to indicate its tax-free status. This approach, while very effective, has shortcomings such as the invasive nature of the tests and/or various deceptive tactics applied by tax evaders. A test designed to detect illicit dyed-fuel use by analyzing the vehicle exhaust would circumvent these shortcomings. This paper describes the development of a simple color spot test designed to detect the use of tax-free (i.e., dyed) fuel by analyzing the engine exhaust. Development efforts first investigated the combustion products of C.I. Solvent Red 164 (the azo dye formulation used in the United States to tag tax-free fuel). A variety of aryl amines were identified as characteristic molecular remnants that appear to survive combustion. A number of micro-analytical color tests specific for aryl amines were then investigated. One test that detected aryl amines by reacting with 4-(dimethylamino)benzaldehyde seemed to be particularly applicable and was used in a proof-of-principle experiment. The 4-(dimethylamino)benzaldehyde color spot test was able to clearly distinguish between engines that were burning regular fuel and those that were burning dyed diesel fuel. Further development will refine this color spot test to provide an easy-to-use field test. PMID- 22063525 TI - A new method for fabricating a CuO/TiO2 nanotube arrays electrode and its application as a sensitive nonenzymatic glucose sensor. AB - In this report, we presented a new method to fabricate TiO(2) nanotube (TiO(2) NT) arrays modified with cupric oxide (CuO) nanofibers, getting a novel TiO(2) NT arrays composition electrode for sensitive nonenzymatic glucose detection. For the preparation of CuO nanofibers, Cu nanoparticles were firstly electrodeposited onto the TiO(2) NT arrays, and then oxidized to CuO nanofibers followed by annealing in air. The CuO nanofibers modified TiO(2) NT (CuO/TiO(2) NT) arrays electrode for electrocatalytic detection of glucose was investigated by cyclic voltammetry and chronoamperometry in 0.10 M NaOH solution. The linear range of detection of glucose extended up to 2.0mM (R=0.997, n=10) at a potential of 0.50 V (vs. SCE). The sensitivity was 79.79 MUA cm(-2)mM(-1), and the detection limit was 1 MUM (S/N=3). Significantly, the poisoning by chloride ion and the interferences from ascorbic acid, uric acid, lactose, sucrose, fructose and dopamine were negligible. Particularly, the CuO/TiO(2) NT arrays electrode showed excellent stability and repeatability over 1 month. The sensor was also investigated detecting glucose in human blood serum samples. PMID- 22063526 TI - Water-soluble fluorescent conjugated polymer-enzyme hybrid system for the determination of both hydroquinone and hydrogen peroxide. AB - In this paper, a sensitive and simple detecting system was developed for quantitative analysis of both hydroquinone (H(2)Q) and hydrogen peroxide (H(2)O(2)), based on the successful combination of horse radish peroxidase (HRP) and water-soluble conjugate fluorescence polymers PPESO(3). In the presence of HRP and H(2)O(2), H(2)Q could be oxidized to 1,4-benzoquinone (BQ), an intermediate, which plays the main role in the enhanced quenching of the photoluminescence (PL) intensity of PPESO(3). The quenching PL intensity of PPESO(3) (I(0)/I) was proportional to the concentration of H(2)Q and H(2)O(2) in the range of 1.0 * 10(-6) to 2.0 * 10(-3)mol/L (R(2)=0.996) and 6.0 * 10(-6) to 2.0 * 10(-3)mol/L (R(2)=0.999), respectively. The detection limit for H(2)Q and H(2)O(2) was 5.0 * 10(-7)mol/L and 1.0 * 10(-6)mol/L, respectively. The present fluorescence quenching method was successfully applied for the determination of H(2)Q in the lake water, rainwater, tap-water and chemical plant wastewater samples. Compared with previous reports, the fluorescence quenching approach described in this work is simple and rapid with high sensitivity, which has a potential application for detecting various analytes which can be translated into quinone. PMID- 22063527 TI - Silica coated gold nanoaggregates prepared by reverse microemulsion method: dual mode probes for multiplex immunoassay using SERS and fluorescence. AB - A kind of fluorescent dye-doped, silica-coated Au aggregates was fabricated using reverse microemulsion method, which shows both strong fluorescence and intense surface enhanced Raman scattering (SERS) signals. Such a composite nanoparticle is composed of a SERS core as silica-coated Au aggregates and a fluorescent shell as dye-doped silica shell. Being prepared through reverse microemulsion method, the SERS core exhibits a sphere shape and a uniform size. Compared with a silica coated single Au nanoparticle, our presented SERS core shows a greatly increased SERS intensity due to the Au aggregates, which is formed by simply mixing the SERS reporters and Au nanoparticles. When being excited at different wavelengths as 515 nm and 633 nm, the fluorescence and SERS signals can be separately generated, which can avoid the disturbance from each other. In addition, the potential application of such a dual mode nanoparticle in multiplex immunoassay was also demonstrated using a sandwiched structure, where the fluorescence mode can be used for indicating the occurrence of an immune reaction, and SERS mode can further be employed for distinguishing the specific kind of bio-analyte. PMID- 22063528 TI - SPE biosensor for cholesterol in serum samples based on electrochemiluminescent luminol copolymer. AB - A poly(luminol-3,3',5,5'-tetramethylbenzidine) copolymer manufactured by electropolymerization on screen-printed gold electrodes greatly improves the electrochemiluminescence of hydrogen peroxide. Cholesterol oxidase was immobilized on the surface of a poly(luminol-3,3',5,5'-tetramethylbenzidine) screen-printed cell modified with chitosan to prepare an ECL biosensor for cholesterol. Working under the optimized conditions, the linear dynamic range of cholesterol was 2.4 * 10(-5)-1.0 * 10(-3)M with a limit of detection of 7.3 * 10( 6)M and a precision of 10.3% (5.0 * 10(-4)M, n=5) expressed as relative standard deviation. This biosensor was applied to the determination of total cholesterol in serum samples obtaining satisfactory results with respect to the reference procedure. This cholesterol biosensor offers an alternative analytical method with low cost and high speed. PMID- 22063529 TI - Screening of 4-androstenedione misuse in cattle by LC-MS/MS profiling of glucuronide and sulfate steroids in urine. AB - The use of anabolic agents in food producing animals is prohibited within the European Union since 1988. The illegal use of natural steroid hormones control is however still a current challenge, especially regarding the limitations of existing screening methods. In this context, the present study aimed to develop a new screening approach based on the emerging 'untargeted profiling' concept, but with a special emphasis on steroids phase II conjugated metabolites, in the scope of revealing potential biomarkers signing a fraudulent administration of 4 androstenedione. After extraction and separation of the urinary glucuronide and sulfate steroid fractions, each one was analyzed separately by UPLC-MS/MS using the precursor ion scan acquisition mode. This approach was carried out in order to monitor product ion characteristic of sulfate (m/z 97) and glucuronide (m/z 113) functional groups, and then to fish for any potential conjugated steroid leading to these ionic species after fragmentation. After statistical analysis, 86 metabolites (33 from steroid compounds and 53 from other unknown substances) were highlighted as potential biomarkers of 4-androstenedione abuse. After application of several robustness criteria, 26 metabolites (whom 5 were unambiguously structurally identified), were finally selected to build a statistical model which could be used as new diagnostic tool for screening purposes. PMID- 22063530 TI - Optimization of the analytical extraction of polyamines from milk. AB - Polyamines play an important role as growth promoters, in the maturation of the intestinal tract of infants and in the modulation of the immune response; consequently, the importance of polyamines in the diet of infants and adults is well established. However, information on the occurrence and levels of polyamines in cow's milk and milk from other species (including human milk) is contradictory. Furthermore, the methods used for the extraction of amines from these samples vary widely. Therefore, a method for the accurate analysis of amines in milk from different species and in milk products is needed. A sequential strategy of experimental designs was used to optimize the analytical extraction of polyamines from milk. The dependent variables that significantly affected the recoveries were screened through a Plackett-Burman design. Sulfosalicylic acid (SSA) provided better recoveries compared to trichloroacetic acid. Centrifugation time and speed during extraction were independent variables. The Central Composite Rotational Design used to optimize the dependent variables indicated that the optimal conditions for the extraction of polyamines were 40s vortexing, four successive extractions, and an SSA concentration of 1.5%. These conditions provided recoveries >= 92.8% and CV <= 5.8%. The experiments confirmed the predicted results, indicating that the optimized conditions and models used were effective in the determination of amines from milk. Samples of raw milk and milk beverages were observed to be poor sources of spermine and spermidine, whereas human milk contained both amines. PMID- 22063531 TI - Functional magnetic nanoparticle-based trapping and sensing approaches for label free fluorescence detection of DNA. AB - In this study, a label-free fluorescence detection method for DNA was designed using functional magnetic nanoparticles (MNPs) as affinity probes. With the advantage of magnetic feature, MNP-based affinity probes can be easily manipulated for trapping and sensing target species. Two types of MNP-based nanoprobes for trapping and detecting target DNAs were fabricated. The basic strategy for this approach is the use of trapping probes to concentrate target DNAs selectively from complex samples. The detection probes are then used as fluorescence reporters to explore the level of the target species. Trapping probes were constructed by covalently immobilizing probe DNA molecules complementary to the target DNA. Detection nanoprobes were made by linking a fluorescent dye, riboflavin-5'-monophosphate (RFMP), onto the surface of the core/shell Fe(3)O(4)@Al(2)O(3) MNPs via Al-phosphate chelation. The fluorescence derived from RFMP molecules became invisible when molecules were attached onto the MNP surface. However, after phosphorylated species (e.g., DNA molecules) replaced RFMP from the surface of the RFMP-Fe(3)O(4)@Al(2)O(3) MNPs under microwave heating for 15s, the RFMP molecules released from the MNPs enhanced the fluorescence intensity in the solution. Based on the measurement of the fluorescence intensity, the level of target DNA in the samples was determined. The remaining DNA molecules on the RFMP-Fe(3)O(4)@Al(2)O(3) MNPs were characterized by using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The detection limit for DNA was as low as 40 pM using this approach. PMID- 22063532 TI - Flow-batch miniaturization. AB - This study introduces the first micro-flow-batch analyzer (MUFBA). A simple, low cost, deep urethane-acrylate photo-resist ultraviolet-lithographic technique was used in its development. Details of the microfabrication process are presented including; the use of two superimposed photo-masks to improve the micro-channel and stop chamber border definition, as well as integration of an LED/phototransistor photometric pair, while using an open nylon-thread (fishing line) micro-mixing system for solutions homogenization. The system was used for photometric determination of Fe(II) in oral solution iron supplements employing the well-known 1,10-phenanthroline method, with instantaneously prepared micro chamber calibration solutions. All analytical processes were accomplished by simply changing the timing parameters in the control software. It must be emphasized here that there was no outside preparation of the standard calibration solutions; the mixing was all done in-chamber/in-line, with all solutions maintained flowing while being proportioned for the measurement processes. The MUFBA results were acceptable when compared to the reference method, and comparable to normal flow-batch systems. It was possible both to project and build a low-cost probe with high sample throughput (about 120 h(-1)), low relative standard deviations (about 1.1%), and reduced reagent consumption (30 times less than the reference method). The MUFBA system based on urethane acrylate presented satisfactory physical and chemical properties while keeping the flexibility, versatility, robustness, and multi-task characteristics of normal flow-batch analyzers. The MUFBA system contributes to the advance of micro analytical instrumentation, while realizing the basic principles of "Green Chemistry". PMID- 22063533 TI - Highly sensitive nonenzymatic glucose sensor based on electrospun copper oxide doped nickel oxide composite microfibers. AB - An improved nonenzymatic glucose sensor based on copper oxide-doped nickel oxide composite microfibers (CuO-NiO-MFs) modified fluorine tin oxide (FTO) electrode was prepared by electrospinning and calcination technologies without using any immobilization. The results of cyclic voltammetry (CV) and chronoamperometry demonstrated that the CuO-NiO-MFs modified electrode displayed much higher electrocatalytic activity than the nickel oxide microfibers (NiO-MFs) modified electrode toward glucose. The nonenzymatic glucose sensor based on CuO-NiO-MFs showed the highest sensitivity of 3165.53 MUA mM(-1)cm(-2) with the lowest detection limit of 1 * 10(-9)M (signal/noise ratio (S/N)=3) in the nonenzymatic glucose sensors that have been reported in the literature. Additionally, its application for detecting glucose concentration of human serum sample showed good agreement with the results obtained from automatic biochemical analyzer. PMID- 22063534 TI - A sensitive and selective method for the determination of flumorph residues in vegetables and fruits by HPLC-ESI-MS/MS. AB - A method has been developed and validated for the quantitative determination of flumorph residues in vegetables and fruits using dimoxystrobin as internal standard (I.S.) by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The conversion rule between flumorph (Z) and flumorph (E) has been studied through sunlight photodegradation test of flumorph. Flumorph and I.S. were extracted with ethyl acetate and preconcentrated by Oasis HLB cartridge. Qualitative and quantitative detection for the analytes were carried out under the multiple reaction monitoring (MRM) in positive ionization mode after chromatography separation on a Symmetry C(18) (150 mm * 2.1 mm * 3.5 MUm) column. Studies at fortification level of 0.05-25 MUg kg(-1) gave mean recoveries from 77.6 to 92.9% for flumorph, with relative standard deviation (R.S.D.) <= 8.7%. The limit of quantification (LOQ, S/N=10) was 0.05 MUg kg(-1). The proposed method was successfully applied on real samples from different kinds of vegetables and fruits. Flumorph residues were detected in 70% of the samples analyzed and the highest concentration level was 1.83 MUg kg(-1) in tomato sample. PMID- 22063535 TI - Electrochemical behavior of azithromycin at graphene and ionic liquid composite film modified electrode. AB - An electrochemical method has been successfully demonstrated for sensitive determination of azithromycin (Azi) with room temperature ionic liquid (IL) of 1 butyl-3-methylimidazolium hexafluorophosphate (BMIMPF(6)) - graphene (Gr) composite modified glassy carbon electrode (GCE). The cyclic voltammetric results indicate that Gr/IL/GCE can remarkably enhance electrocatalytic activity towards the oxidation of Azi in neutral solutions. Azi produce an anodic peak at about 0.82 V at this electrode. The electrocatalytic behavior was further exploited as a sensitive detection scheme for the Azi determination by differential-pulse voltammetry (DPV). Under optimized conditions, the concentration range and detection limit were 0.49-28.57 MUg ml(-1) and 0.19 MUg ml(-1) (S/N=3) respectively for Azi. The method was successfully applied assay of the drug in the pharmaceutical dosage forms. PMID- 22063536 TI - Blood matrix effects for male and female Wistar rats, in simultaneous HPLC-UV determination of riparin I and III from Aniba riparia (Nees) Mez. (Lauraceae). AB - Aniba riparia (Nees) Mez. (Lauraceae) is popularly known as "louro", and is found in Amazonia and in the Guianas, its distribution extends to the Andes. Alkamide alkaloids were isolated from its green fruit; they were denominated riparin I (methyl ether of N-benzoyl tyramine), riparin II (methyl ether of N-2-hydroxy benzoyl tyramine) and riparin III (methyl ether of N-2,6-dihydroxy-benzoyl tyramine) in tribute to the plant. When administered orally and intraperitoneally to mice, riparin I and III are anxiolytic, yet without any sedative or muscle relaxing effects. The present study shows that variables such as extraction solvent, centrifugation force, and centrifugation time, are important in the simultaneous liquid-liquid extraction of riparin I and III from male and female Wistar rat blood in HPLC-UV studies. The study confirms matrix influence on simultaneous recovery and detection of riparin I and III. The effect of rat blood matrix for riparin I was -13.86%, while for riparin III it was -10.94%. The recovery for riparin I was 82.14%, while for riparin III it was 87.42%. The efficiency of the process was 73.25% for riparin I and 77.81% for riparin III, demonstrating an optimal method for simultaneous recovery of riparins I and III from the blood of rats. The matrix effect for rat blood showed values of 10.25% for riparin I and -83.01% for riparin III. Recovery for riparin I was 113.11%, whereas for riparin III it was 13.65%. The process efficiency of this method for female rat blood was 125.88% for riparin I and 2.58% for riparin III. Simultaneous recovery of riparin I and III from the blood of male and female rats using acetonitrile as the precipitating solvent, while centrifuged at 10,000 * g for 10 min demonstrated the importance of the parameters chosen for the extraction/recovery process of different analytes. PMID- 22063537 TI - Performance evaluation of collision-reaction interface and internal standardization in quadrupole ICP-MS measurements. AB - The combined use of internal standardization with collision and reaction interface in an inductively coupled plasma quadrupole mass spectrometer (ICP-QMS CRI) was evaluated. The behavior of several elements (Ba, Cd, Co, Cr, Cu, Li, Mn, Mo, Pb, Sb, V and Zn) was studied by introducing H(2) or He through the skimmer and sampler cones of the CRI device and by using In, Rh and Sc as internal standards. Certified reference material of trace elements in water (NIST 1643e) was used to evaluate the performance of the method. A vinegar sample and mixed food diet standard reference material were directly introduced into the equipment as complex matrices for Cr and V determinations. Improvements in accuracy and precision were attained combining both strategies. The introduction of H(2) through the skimmer cone was the best way to overcome polyatomic ions formation and to improve SBR and BEC values for several elements. The use of Sc as internal standard improved the performance of ICP-QMS-CRI. PMID- 22063538 TI - Magnetic multi-walled carbon nanotubes assisted dispersive solid phase extraction of nerve agents and their markers from muddy water. AB - The multi-walled carbon nano-tubes (MWCNT) were magnetized with iron oxide nanoparticles and were characterized by SEM and EDX analyses. These magnetized MWCNT (Mag-CNT) were used as sorbent in dispersive solid phase extraction (DSPE) mode to extract nerve agents and their markers. Mag-CNT were dispersed in water and collected with the help of an external magnet. From Mag-CNT, the adsorbed analytes were eluted and analyzed by GC-FPD in phosphorus mode. DSPE was found to be advantageous over conventional solid phase extraction (SPE) in terms of operational simplicity, speed, handling of large sample volume and recoveries. Extraction parameters such as eluting solvent, sorbent amount, pH and salinity of aqueous samples were optimized. Optimized extraction conditions included 40 mg of Mag-CNT as sorbent, chloroform as eluent, pH 3-11 and salinity 20%. Under the optimized conditions, recoveries from distilled water ranged from 60 to 96% and were comparable in tap and muddy water. Limits of quantification and limits of detection of 0.15 ng/ml and 0.05 ng/ml, respectively, were achieved. Superiority of Mag-CNT over conventional C(18) SPE was also established. PMID- 22063539 TI - Scope of detection and determination of gallium(III) in industrial ground water by square wave anodic stripping voltammetry on bismuth film electrode. AB - Gallium(III) in ground water may cause human health hazards due to the antineoplastic and antimicrobial activities of gallium. However, the exposure limit of Ga(III) has not been set. This paper demonstrates the scope of employing the square wave anodic stripping voltammetry (SWASV) on bismuth film electrode (BiFE) for selective and sensitive detection of Ga(III) as well as its accurate and precise determination. The key parameters were optimized and the bismuth film morphology was characterized. The performance of BiFE was also compared with that of the mercury film electrode (MFE). The performance of BiFE was also studied for interferences of Zn(II), Cd(II), Tl(I) and Cu(II) ions. Gaussian peak fitting was performed to improve the calibration curve and the fitting process revealed almost similar stripping peak heights as obtained from the experimentally observed data though slight improvement in calibration was obtained from the peak area analysis. A good linear dynamic range (R(2)=0.996) was obtained in the concentration range of 20-100 MUg/L with a limit of detection (LOD) of 6.6 MUg/L (S/N=3) of Ga(III). A relative standard deviation of 2.9% (n=10) was obtained for 20 MUg/L of Ga(III) solution. The practical analytical utility of the method was verified by the determination of Ga(III) in spiked water samples, where 100-105% recovery of Ga(III) was achieved. PMID- 22063540 TI - A hydrogen peroxide sensor based on Ag nanoparticles electrodeposited on natural nano-structure attapulgite modified glassy carbon electrode. AB - A novel strategy to fabricate hydrogen peroxide (H(2)O(2)) sensor was developed by electrodepositing Ag nanoparticles (NPs) on a glassy carbon electrode modified with natural nano-structure attapulgite (ATP). The result of electrochemical experiments showed that such constructed sensor had a favorable catalytic ability to reduce H(2)O(2). The good catalytic activity of the sensor was ascribed to the ATP that facilitated the formation and homogenous distribution of small Ag NPs. The resulted sensor achieved 95% of the steady-state current within 2s and had a 2.4 MUM detection limit of H(2)O(2). PMID- 22063541 TI - A novel biosensor based on serum antibody immobilization for rapid detection of viral antigens. AB - In this paper, we represent a label-free biosensor based on immobilization of serum antibodies for rapid detection of viral antigens. Human serum containing specific antibodies against Japanese encephalitis virus (JEV) was immobilized on a silanized surface of an interdigitated sensor via protein A/glutaraldehyde for electrical detection of JEV antigens. The effective immobilization of serum antibodies on the sensor surface was verified by Fourier transform infrared spectrometry and fluorescence microscopy. The signal of the biosensor obtained by the differential voltage converted from the change into non-Faradic impedance resulting from the specific binding of JEV antigens on the surface of the sensor. The detection analyzed indicates that the detection range of this biosensor is 1 10 MUg/ml JEV antigens, with a detection limit of 0.75 MUg/ml and that stable signals are measured in about 20 min. This study presents a useful biosensor with a high selectivity for rapid and simple detection of JEV antigens, and it also proposes the biosensor as a future diagnostic tool for rapid and direct detection of viral antigens in clinical samples for preliminary pathogenic screenings in the case of possible outbreaks. PMID- 22063542 TI - A combination of single-drop microextraction and open tubular capillary electrochromatography with carbon nanotubes as stationary phase for the determination of low concentration of illicit drugs in horse urine. AB - In this study we developed an interesting alternative to HPLC-mass spectrometry for the quantification of seven important drugs of abuse in racehorses. The procedure proposed in this work is a combination of single-drop microextraction (SDME) and an open tubular capillary electrochromatography (OT-CEC) using multi wall carbon nanotubes (MWCTs) immobilized into a fused-silica capillary as a stationary phase. The SDME showed to be a powerful tool for extraction/preconcentration of the seven drugs analyzed in the study, showing an enrichment factor between 38- and 102-fold depending on the drug. We have investigated the electrophoretic features of MWCTs immobilized fused-silica capillary by covalent modification of the inner surface of the capillary. The results show a good run-to-run, day-to-day and capillary-to-capillary reproducibility of the method. Compared with the capillary zone electrophoresis (CZE), the coating of the capillary allowed the separation of the analytes with high resolution, with less band-broadening and without distortion of the baseline. The interactions between the analytes and the MWCTs resulted in an increased migration time and probably this was the reason of the front tailing effect. The results showed a good capillary efficiencies and an improved of the electrophoretic separation. PMID- 22063543 TI - Rapid and semi-quantitative presumptive tests for opiate drugs. AB - Digital image analysis was applied to the products of simple colour presumptive tests for opiates. Adobe Photoshop software was used for colour analysis to obtain analytical data in the form of a Red Green Blue (RGB) value. Calibration curves were developed for morphine, codeine, and diamorphine hydrochloride and the developed tests successfully applied to seized heroin samples to demonstrate the application of the technique in a forensic case context. Good agreement with gas chromatographic quantification results was obtained for the illicit samples analysed and a wide linear range and low detection limit for all drugs under test facilitated the application to illicit samples. The results show great potential for use as a semi-quantitative field test for illicit drug compounds. PMID- 22063544 TI - Development of a fast and reliable method for long- and short-term wine age prediction. AB - Wine age prediction based on its intrinsic characteristics can provide significant assistance to oenologists' quality evaluations, concerning wine ageing process control and wine quality assurance. Simpler, faster, cheaper and affordable analytical procedures would be greatly welcome to establish such a practice. In this study, we present a new and reliable strategy to predict wine age, in the long and short-term, centered on the use of wine UV-vis absorbance data, coupled with proper chemometric techniques. The strategy followed consists essentially in first pre-processing the UV-vis data, secondly to carry out variable selection over such pre-processed data sets, and finally to use the set of selected variables for developing a PLS model focused on wine age prediction. We tested different data pre-processing methodologies, namely first and second derivatives, multiplicative scatter correction, standard normal variate and orthogonal signal correction, as well as different variable selection approaches, specifically interval partial least squares, VIPS, genetic algorithms and the wavelet transformation combined with a genetic algorithm. In both case studies, regarding long and short-term ageing periods, we have found out that it is indeed possible to predict wine ages, in our case Madeira wine ages, with an accuracy of 1.4 years for longer ageing periods, and of 3 months for wines of an age comprised in the first two years of ageing. The genetic algorithm revealed to be very useful for proper wavelet coefficients selection, leading to the most parsimonious model among all those analyzed, which also presents the best predictive performance found. PMID- 22063545 TI - Using proteolytic enzymes to assess metal bioaccessibility in marine sediments. AB - In this work we tested two proteolytic enzymes (trypsin and pepsin) to evaluate metal bioaccessibility in marine sediments. Some working conditions were studied, in particular incubation time, enzyme concentration and solution/solid ratio, and metals release mechanisms were investigated using both untreated and denatured enzymes. The results obtained with trypsin and pepsin were compared with each other and with results from proteinase K extraction, carried out on the same sediment samples, following a procedure reported in the literature. Moreover, a comparison with the first step of BCR sequential procedure was made. Metal orders of mobility determined with the different enzymes and with acetic acid were compared with the one defined by the enrichment factors in the gut fluids of deposit-feeder organisms. The overall picture suggests that proteinase K has a better capability of reproducing natural phenomena and is therefore more suitable to determine metal bioaccessibility in marine sediments, when the target of the investigation is deposit-feeder organisms. PMID- 22063546 TI - 1H NMR variable selection approaches for classification. A case study: the determination of adulterated foodstuffs. AB - Whenever dealing with large amount of data as is the case of a NMR spectrum, carrying out a variable selection before applying a multivariate technique is necessary. This work applies various variable selection techniques to extract relevant information from (1)H NMR spectral data. Three approaches have been chosen, because each is based on very different foundations. The first method, called Xdiff, is based on calculating the normalized differences between the mean spectrum of a class considered to be the reference and the spectra of each sample. The second approach is the interval Partial Least Squares method (iPLS), which investigates the influential zones of the spectra that contains the most discriminating predictors calculating local PLS-DA models on narrow intervals. The last one is Genetic Algorithms (GAs) which finds the optimal variables from a random initial subset of variables by means of an iterative process. The performance of each variable selection strategy is determined by the classification results obtained when multiclass Partial Least Squares Discriminant Analysis is applied. This study has been applied to NMR spectra of culinary spices that might be adulterated with banned dyes such as Sudan dyes (I IV). The three techniques give neither the same number nor the same selected variables, but they do select a common zone from the spectra containing the most discriminating variables. All three techniques give satisfactory classification and prediction results, being higher than 95% with iPLS and GA and around 89% with Xdiff, therefore the three variable selection techniques are suitable to be used with NMR data in the determination of food adulteration with Sudan dyes as well as the specific type of adulterant used (I-IV). PMID- 22063547 TI - Fabrication and characterization of disposable sensors and biosensors for detection of formaldehyde. AB - Screen-printed carbon electrodes (SPCEs) electrochemically platinised (Pt-SPCEs) and screen-printed platinised carbon electrodes (SPC(Pt)Es) have been chronoamperometrically characterized for the determination of formaldehyde (FA). The oxidation current registered at 600 mV in the FA concentration range from 0.99 to 9.09 mmol L(-1), led to higher precision values in terms of repeatability and reproducibility when using SPC(Pt)Es. SPC(Pt)Es have been also used for alcohol oxidase (AOX) cross-linked immobilization in the development of enzymatic biosensors for FA. The enzymatic reaction produces hydrogen peroxide, which has been chronoamperometrically monitored and related to FA concentration in different kinds of samples. Experimental design methodology has been performed to optimize the pH and the applied potential. This method has shown a repeatability and reproducibility of 3% (n=4) and 6% (n=4) respectively, related to the slopes of the calibration curves performed in the range from 60 to 460 MUmol L(-1). The use of this kind of biosensor, which has a detection capability of 60 MUmol L(-1) for a given probability of false positive and negative equal to 0.05, has been probed in the determination of FA in commercial samples for histology. PMID- 22063548 TI - Analysis of perfluorinated phosponic acids and perfluorooctane sulfonic acid in water, sludge and sediment by LC-MS/MS. AB - Residues of perfluorinated phosphonic acids (PFPAs) and perfluorooctane sulfonic acid (PFOS) were investigated in various Dutch surface waters, sludge and sediments. For this purpose, a liquid chromatographic (LC) method was optimized by testing several columns with different mobile phases. Atmospheric pressure chemical ionization (APCI) was chosen for the LC tandem mass spectrometry (MS/MS) analysis. An ion-pair reagent was added to the injection solvent to improve peak shape. Different solvents were studied for the extraction from solid samples. For clean-up and pre-concentration, weak anion-exchange solid-phase extraction cartridges were used. Water samples were extracted using the same cartridges. The method was used for screening PFPAs in the Dutch aquatic environment. PFPAs were not observed in sediment or sludge samples. PFOPA was found at 1 ng L(-1) in one surface water sample. PFOS was found at levels between 0.07 ng g(-1) and 48 ng g( 1) (dry weight) in sediments and sewage sludge samples. PFOS concentrations in surface water ranged from 3.3 ng L(-1) to 25.4 ng L(-1). PMID- 22063549 TI - Development of phosphonate modified Fe 1-x MnxFe2O4 mixed ferrite nanoparticles: novel peroxidase mimetics in enzyme linked immunosorbent assay. AB - A highly facile and feasible strategy on the fabrication of advanced intrinsic peroxidase mimetics based on Mn(2+) doped mixed ferrite (Mn(II)(x)Fe(II)(1 x)Fe(III)(2)O(4)) nanoparticles was demonstrated for the quantitative and sensitive detection of mouse IgG (as a model analyte). Mn(2+) doped Fe(1 x)Mn(x)Fe(2)O(4) nanoparticles were synthesized using varying ratios of Mn(2+):Fe(2+) ions and characterized by the well known complementary techniques. The increase of Mn(2+) proportion had remarkably enhanced the peroxidase activity and magnetism. The catalytic activity of mixed ferrites was found to follow Michaelis-Menten kinetics and was noticeably higher than native Fe(3)O(4). The calculated K(m) and K(cat) exhibited strong affinity with substrates which were remarkably higher than similar sized native magnetite nanoparticles and horseradish peroxidase (HRP). These findings stimulated us to develop carboxyl modified Fe(1-x)Mn(x)Fe(2)O(4) nanoparticles using phosphonomethyl immunodiacetic acid (PMIDA) to engineer PMIDA-Fe(1-x)Mn(x)Fe(2)O(4) fabricated enzyme linked immunosorbent assay (ELISA). Results of both PMIDA-Fe(1-x)Mn(x)Fe(2)O(4) linked ELISA revealed that the enhancements in absorbance during the catalysis of enzyme substrate were linearly proportional to the concentration of mouse IgG within the range between 0.1 MUg/ml and 2.5 MUg/ml. Further, this detection was ten times lower than previous reports and the detection limit of mouse IgG was 0.1 MUg/ml. The advantages of our fabricated artificial peroxidase mimetics are combined of low cost, easy to prepare, better stability and tunable catalytic activity. Moreover, this method provides a new horizon for the development of promising analytical tools in the application of biocatalysis, bioassays, and bioseparation. PMID- 22063550 TI - An improved high performance liquid chromatography-photodiode array detection atmospheric pressure chemical ionization-mass spectrometry method for determination of chlorophylls and their derivatives in freeze-dried and hot-air dried Rhinacanthus nasutus (L.) Kurz. AB - Rhinacanthus nasutus (L.) Kurz, a traditional Chinese herb possessing antioxidant and anti-cancer activities, has been reported to contain functional components like carotenoids and chlorophylls. However, the variety and amount of chlorophylls remain uncertain. The objectives of this study were to develop a high performance liquid chromatography-photodiode array detection-atmospheric pressure chemical ionization-mass spectrometry (HPLC-DAD-APCI-MS) method for determination of chlorophylls and their derivatives in hot-air-dried and freeze dried R. nasutus. An Agilent Eclipse XDB-C18 column and a gradient mobile phase composed of methanol/N,N-dimethylformamide (97:3, v/v), acetonitrile and acetone were employed to separate internal standard zinc-phthalocyanine plus 12 cholorophylls and their derivatives within 21 min, including chlorophyll a, chlorophyll a', hydroxychlorophyll a, 15-OH-lactone chlorophyll a, chlorophyll b, chlorophyll b', hydroxychlorophyll b, pheophytin a, pheophytin a', hydroxypheophytin a, hydroxypheophytin a' and pheophytin b in hot-air-dried R. nasutus with flow rate at 1 mL/min and detection at 660 nm. But, in freeze-dried R. nasutus, only 4 chlorophylls and their derivatives, including chlorophyll a, chlorophyll a', chlorophyll b and pheophytin a were detected. Zinc-phthalocyanine was found to be an appropriate internal standard to quantify all the chlorophyll compounds. After quantification by HPLC-DAD, both chlorophyll a and pheophytin a were the most abundant in hot-air-dried R. nasutus, while in freeze-dried R. nasutus, chlorophyll a and chlorophyll b dominated. PMID- 22063551 TI - Comparison of headspace solid-phase microextraction with conventional extraction for the analysis of the volatile components in Melia azedarach. AB - The volatile compositions of Melia azedarach were studied by headspace solid phase microextraction (HS-SPME). The result was compared with that obtained by soxhlet extraction (SE) and ultrasonic extraction (UAE). 79 compounds were identified in this study, among which 64 compounds were first reported. The experimental parameters including fiber type (PDMS, PDMS-DVB and CAR-PDMS), desorption time, extraction temperature and time were investigated. 37 compounds were obtained by HS-SPME, including curcumene (33.25%), alpha-cadinol (11.16%), alpha-muurolene (8.72%), copaene (5.04%), beta-bisabolene (3.41%), and alpha selinene (2.97%). The result suggested that the HS-SPME method is a powerful analytic tool and complementary to traditional methods for the determination of the volatile compounds in Chinese herbs. PMID- 22063552 TI - Development of a new in vitro method to evaluate the photoprotective sunscreen activity of plant extracts against high UV-B radiation. AB - Sunscreen efficiency of biomolecules against UV-B radiation was generally determined in vitro by cosmetic methods which are not well-adapted for routine ecophysiological and bio-guidance studies in plant research laboratories. In this article, we propose a new in vitro method to evaluate the sunscreen photoprotective activity of plant extracts against high UV-B radiation. Because photosynthetic pigments are one of the first targets of UV-B radiation in plants, the experimental design is based on the ability of the tested substances to limit the degradation of sodium magnesium chlorophyllin (SMC), a derivative compound of natural chlorophyll. SMC photodegradation comparatively to natural chlorophyll and related to temperature, concentration and sample solvent were analyzed in order to optimize the experimental parameters. Then, the method was validated by testing nine standard UV filters used in the European cosmetic industry and by comparing results of their activity with those of a reference in vitro procedure. Finally, the method was applied to coastal and marine crude plant extracts. Results have shown that our procedure can be a good alternative to cosmetic methods with a rapid, sensitive and reproducible evaluation of the sunscreen activity of either pure standards or crude plant extracts in small amounts (30 mg). PMID- 22063553 TI - Optimization of the ion chromatographic quantification of airborne fluoride, acetate and formate in the Metropolitan Museum of Art, New York. AB - Ion chromatographic (IC) methods have been compared in order to achieve an optimal separation of fluoride, acetate and formate under various elution conditions on two formerly introduced analytical columns (i and ii) and a novel one (iii): (i) an IonPac AS14 (250 mm * 4 mm I.D.), (ii) Allsep A-2 (150 mm * 4.6mm I.D.), and (iii) an IC SI-50 4E (250 mm (length) * 4mm (internal diameter - I.D.)). The IC conditions for the separation of the anions concerned were optimized on the IC SI-50 4E column. A near baseline separation of these anions was attained on the IonPac AS14, whereas the peaks of fluoride and acetate could not be resolved on the Allsep A-2. A baseline separation for the three anions was achieved on the IC SI-50 4E column, when applying an eluent mixture of 3.2 mmol/L Na(2)CO(3) and 1.0 mmol/L NaHCO(3) with a flow rate of 1.0 mL/min. The highest precision of 1.7, 3.0 and 2.8% and the best limits of detection (LODs) of 0.014, 0.22 and 0.17 mg/L for fluoride, acetate and formate, respectively, were obtained with the IC SI-50 4E column. Hence, this column was applied for the determination of the acetic and formic acid contents of air samples taken by means of passive gaseous sampling at the Metropolitan Museum of Art in New York, USA. Atmospheric concentrations of acetic and formic acid up to 1050 and 450 MUg/m(3), respectively, were found in non-aerated showcases of the museum. In galleries and outdoors, rather low levels of acetic and formic acid were detected with average concentrations of 50 and 10 MUg/m(3), respectively. The LOD data of acetate and formate on the IC SI-50 4E column correspond to around 0.5 MUg/m(3) for both acetic and formic acid in air samples. PMID- 22063554 TI - Surface plasmon resonance based immunosensor for the detection of the cancer biomarker carcinoembryonic antigen. AB - An immunoassay in optimised conditions with a highly sensitive surface plasmon resonance (SPR) based biosensor was developed for the detection of the cancer biomarker carcinoembryonic antigen (CEA). Different formats of the immunoassay were initially investigated on the surface of the gold sensor chip. A self assembled monolayer (SAM) was formed on the gold chip using 11-mercaptoundecanoic acid (MUDA), before the immobilisation of the antibodies was conducted. The assay was then formed in a direct capture and a sandwich assay. In order to increase the sensor signal the CEA antigen was incubated with the detection/capture antibody before it was injected to the sensor chip surface and the results were recorded in real-time using the Biacore 3000 instrument. A detection limit of 3 ng ml(-1) CEA was obtained with a dynamic detection range from 3 ng ml(-1) to 400 ng ml(-1) with correlation coefficients of 1.00 and 0.99 for the sandwich and rabbit anti-mouse (RAM) capture assay. Kinetic data analysis was performed for the standard capture test and subsequently for the developed assays and R(max) showed an increase from 215 RU for the standard capture test to 428 RU for the RAM-capture assay and 734 RU for the sandwich assay, respectively. The developed SPR immunosensor using the sandwich assay format showed high sensitivity and reproducibility for CEA detection which makes it a promising procedure for cancer biomarker analysis. PMID- 22063555 TI - Simultaneous determination of alcohol and carbohydrate content in commercial beverages by ultrasound frequency analysis. AB - Controlling the composition of commercial beverages is critical for quality control. Rapid on-line measurements would allow optimization in real time. We have developed a methodology to monitor the volume fraction of ethanol and the carbohydrate concentrations in liquid mixtures using ultrasound frequency analysis. Characteristic distortion to ultrasound waves propagating through liquids is induced by the specific chemical composition of the mixture. The distortion induced by the hydrogen bonding between water, ethanol, and sucrose can be monitored in the frequency domain using 5 MHz wideband ultrasonic transducers. Multilinear regression was used to quantify both ethanol and sucrose over a wide range of concentrations with correlation coefficients (r(2)) greater than 0.98. Calibrations based on prepared solutions were then used to estimate the ethanol volume and carbohydrate concentration in 22 commercial beverages ranging from sodas to distilled alcohols. Results indicate that the ethanol and carbohydrates could be estimated with a 3.18% and 0.032 g/mL error, respectively. Further, by focusing the analysis over a limited range, the error could be reduced to 0.81% ethanol. This technique demonstrates a strong potential for rapid, in situ monitoring of beverage production, which excludes sample extraction and pretreatment. PMID- 22063556 TI - A novel electrochemical sensor for assaying of antipsychotic drug quetiapine. AB - A novel electrochemical sensor based on poly(2-hydroxy-5-[(4 sulfophenyl)azo]benzoic acid) film modified glassy carbon electrode for fast and simple quantification of trace amount of quetiapine fumarate (QF) was developed. It exhibits excellent enhancement effects on the electrooxidation of QF facilitating preconcentration of drug molecules on the electrode surface. Based on its strong adsorptive activity, the concentration of QF in pharmaceutical formulations and biological fluids was determined directly by voltammetry with excellent sensitivity and high selectivity. The introduction of carboxylated and sulfonated functionalities in polymer film improves the uniform selectivity for positively charged target QF molecules. The calibration curve is linear in QF concentration range of 8.0 * 10(-8) to 7.5 * 10(-6)M with detection limit 1.9 * 10(-8) and sensitivity 8.96 * 10(5) MUA M(-1). The presented sensor has long term stability and good reproducibility with benefits of fast response time, ease of preparation and regeneration of the surface that makes the proposed method useful in the determination of QF in real samples. PMID- 22063557 TI - Highly sensitive amperometric detection of bilirubin using enzyme and gold nanoparticles on sol-gel film modified electrode. AB - We describe the development of a simple and highly sensitive electrochemical (amperometric) sensing of bilirubin based on bilirubin oxidase (BOx) incorporated into the gold nanoparticles (AuNPs). This nanoelectrode platform with self assembled enzyme is highly sensitive toward the electrochemical oxidation of bilirubin and increased the bilirubin concentration linearly from 1 to 5000 MUM with a correlation coefficient of 0.9960, and an apparent Michaelis constant (K(M,app)) of 44 +/- 0.4 MUM. Using an amperometric method, the detection limit for bilirubin at the enzyme-modified electrode was 1.4 nM (signal-to-noise ratio=3). The modified electrode retained a stable response for 2 days while losing only ca. 3.4% of its initial sensitivity during a 10 days storage period in 0.2M phosphate buffer solution (pH=8.4) at <= 4 degrees C. The practical application of the modified electrode was demonstrated by measuring the concentration of bilirubin in blood serum sample. PMID- 22063558 TI - Dye-functional mesoporous silica material for fluorimetric detection of Cr(III) in aqueous solution and biological imaging in living systems. AB - A dye-functionalized silica nanomaterial, SBA-RT was prepared by the immobilization of the Rhodamine-based chemosensor R6G-TETA within the channels of SBA-15. SBA-RT exhibits several different properties compared to the free R6G TETA, such as higher selectivity, blue-shift of the UV-vis spectra due to special spatial environment in the channels of the mesoporous material. It presents Cr(III)-selective fluorimetric and colorimetric responses in aqueous solution. The fluorescence responses are reversible by treating with EDTA and do not vary over a broad pH range suitable for Cr(III) bioimaging application. Through isolating of the metal ions within the mesopores of the silica, SBA-RT can extract Cr(III) from the solution with only trace amounts remaining. The fluorescence images experiment demonstrated the possibility of further application in monitoring Cr(III) in living cells and organisms. PMID- 22063559 TI - Steroid hormones analysis with surface-assisted laser desorption/ionization mass spectrometry using catechin-modified titanium dioxide nanoparticles. AB - This paper describes the application of catechin-modified titanium dioxide nanoparticles (TiO(2) NPs) as matrices to analyze four steroid hormones by surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). The catechin-modified TiO(2) NPs have high absorbance at 337 nm and are effective SALDI matrices when using a nitrogen laser. Four test steroid hormones-cortisone, hydrocortisone, progesterone, and testosterone-were directly analyzed by SALDI MS. The limits of detection at a signal-to-noise ratio of 3 for cortisone, hydrocortisone, progesterone, and testosterone were 1.62, 0.70, 0.66, and 0.23 MUM, respectively. This approach provides good quantitative linearity for the four analytes (R(2)>0.986) with good reproducibility (the shot-to-shot and batch to-batch variations for the four analytes were less than 10% and 15%, respectively). We validated the practicality of this approach-considering its advantages in sensitivity, repeatability, rapidity, and simplicity-through the analysis of testosterone in a urine sample. PMID- 22063560 TI - Reflection spectroscopy for the determination of Au nanostructure formation on carbon surfaces. AB - Au electrodeposition has been performed on carbon electrodes to fabricate Au nanostructures on the working electrode of screen-printed carbon chips. The amount of Au deposited was characterized using the raw reflection spectra obtained by detecting UV-Vis spectrum reflected from the electrode surface. SEM images at different deposition time points provided evidence for the growth of Au nanostructures. The increase in deposition time led to an increase in the intensity of the spectrum obtained for both chips. The acquired optical properties of the carbon chips provide a promising platform for simultaneous optical and electrochemical measurements. PMID- 22063561 TI - Bioaccessibility of essential elements from white cheese, bread, fruit and vegetables. AB - Bioaccessibility of five essential micronutrients (iron, zinc, copper, manganese and molybdenum) from the Lebanese food basket including bread, different varieties of white cheese, fruit and vegetables was evaluated using the in vitro gastrointestinal digestion model. Only very small fraction of Fe and Zn (ca. 10%) was found bioaccessible from bread, squash and cucumber. Iron in apple was not bioaccessible either (<10%) but apples were found to be a good source of Zn (56%). Most of iron (>50%) in cheese was found to be bioaccessible but only one type of cheese, double creme, contained readily bioaccessible zinc. More than 50% of copper and molybdenum was found bioaccessible regardless of the investigated food. High bioaccessibility (>50%) was also observed for manganese in fruit and vegetables whereas that from bread and cheese was fair (25-30%). PMID- 22063562 TI - Urea free and more efficient sample preparation method for mass spectrometry based protein identification via combining the formic acid-assisted chemical cleavage and trypsin digestion. AB - A formic acid (FA)-assisted sample preparation method was presented for protein identification via mass spectrometry (MS). Detailedly, an aqueous solution containing 2% FA and dithiothreitol was selected to perform protein denaturation, aspartic acid (D) sites cleavage and disulfide linkages reduction simultaneously at 108 degrees C for 2h. Subsequently, FA wiped off via vacuum concentration. Finally, iodoacetamide (IAA) alkylation and trypsin digestion could be performed ordinally. A series of model proteins (BSA, beta-lactoglobulin and apo Transferrin) were treated respectively using such method, followed by matrix assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The identified peptide number was increased by ~ 80% in comparison with the conventional urea-assisted sample preparation method. Moreover, BSA identification was achieved efficiently down to femtomole (25 +/- 0 sequence coverage and 16 +/- 1 peptides) via such method. In contrast, there were not peptides identified confidently via the urea-assisted method before desalination via the C18 zip tip. The absence of urea in this sample preparation method was an advantage for the more favorable digestion and MALDI-TOF MS analysis. The performances of two methods for the real sample (rat liver proteome) were also compared, followed by a nanoflow reversed-phase liquid chromatography with electrospray ionization tandem mass spectrometry system analysis. As a result, 1335 +/- 43 peptides were identified confidently (false discovery rate <1%) via FA-assisted method, corresponding to 295 +/- 12 proteins (of top match=1 and requiring 2 unique peptides at least). In contrast, there were only 1107 +/- 16 peptides (corresponding to 231 +/- 10 proteins) obtained from the conventional urea-assisted method. It was serving as a more efficient protein sample preparation method for researching specific proteomes better, and providing assistance to develop other proteomics analysis methods, such as, peptide quantitative analysis. PMID- 22063563 TI - A novel direct-injection photometric detector integrated with solenoid pulse-pump flow system. AB - A novel flow photometric detector based on paired emitter-detector diodes (PEDD), coupled with solenoid pulse micro-pumps is presented. The photometric detection chamber also plays a role of the reaction chamber. Both solutions, a sample and a reagent, are injected by solenoid micro-pumps directly and simultaneously into the chamber in countercurrent. This method ensures fast and effective mixing of the injected solutions. A good accuracy and precision of the injected volumes assure the pulse micro-pumps. This method, in comparison with other flow methods, does not require the application of the reaction coil. Thanks to this, the dispersion of the sample is minimized. The presented flow network is easy to control, miniaturize and exhibits a very low consumption of reagents and the sample. Two chemical systems were chosen and presented as models of photometric reactions: the first - Fe(III) with thiocyanate, and the second - Cr(VI) with 1,5 diphenylcarbazide. To obtain the highest repeatability, the total volume of the solutions should be smaller than the volume of the reaction-detection chamber. In this case, the whole coloured product remains in the chamber. The use of the proposed direct-injection PEDD detector considerably simplifies analytical procedures. The shape of analytical signals and their potential applications have been discussed. PMID- 22063564 TI - Ultrasonic energy as a tool to overcome some drawbacks in the determination of lead in brain tissue and urine of rats. AB - An ultrasonic assisted solid-liquid extraction method was developed to determine the level of lead in the brain and urine of rats. Lead was determined by electrothermal atomic absorption spectrometry with longitudinal-Zeeman background correction. Several analytical drawbacks were addressed and overcome, namely small brain sample mass and the formation of precipitate in the urine samples. Utrasonication provided by an ultrasonic probe succeeded in extracting lead from brain samples. Furthermore, it was demonstrated that the formation of a precipitate lowered the lead content in the liquid phase of the urine. Lead was back extracted from the precipitate to the liquid phase with the aid of ultrasonic energy and acidifying the urine with 10% v/v nitric acid. A microwave assisted acid digestion protocol was used to check the completeness of the lead extraction. The within bath and between bath precision was 5% (n=9) and 7% (n=3) respectively. The limit of quantification was 1.05 MUg g(-1) for brain samples and 2.1 MUg L(-1) for urine samples. A total of 6 samples of urine and 12 samples of brain from control rats and another 6 samples of urine and 12 samples of brain from rats fed with tap water rich in lead acetate were used in this research. Lead levels in brain and urine from exposed rats ranged from 1.9 +/- 0.2 MUg g( 1) to 3.5 +/- 0.2 MUg g(-1) and from 752 +/- 56 MUg L(-1) to 60.9 +/- 1.2 mg L( 1) respectively. Statistically significant differences of levels of lead in brain and urine were found between exposed and non exposed rats. PMID- 22063565 TI - Determination of dissociation parameters of weak acids in different media according to the isohydric method. AB - The isohydricity (pH constancy) principle is referred to the pair of solutions: weak acid (HL, C(0)mol/L) and strong acid (HB, C mol/L) when mixed e.g., according to titrimetric mode. Such a case takes place if the relation C(0)=C+C(2) * 10(pK(1)) is valid, where pK(1)=-log K(1), K(1) - dissociation constant for a weak monoprotic acid HL. This principle, outlined and formulated in earlier paper (Michalowski et al., Talanta 82 (2010) 1965), is the basis for a sensitive method of pK(1) determination, confirmed for a series of weak acids in presence of basal electrolytes or in water+organic solvent (dimethyl sulphoxide, methanol, isopropanol) media. The results of titrations were elaborated according to principles of regression analysis, with use of least squares method. A new criterion for precision of the results obtained according to this method is formulated. The pK(1) values obtained are comparable with ones found in literature. PMID- 22063566 TI - Synthesis and enantioseparation characteristics of a novel mono-6-deoxy-(2,4 dihydroxybenzimide)-beta-cyclodextrin as a chiral stationary phase in high performance liquid chromatography. AB - A novel chiral selector mono-6-deoxy-(2,4-dihydroxybenzimide)-beta-CD (MDHB-beta CD) in which the derivatized group and the cavity of CD is linked by CH(2)-N=C group, was successfully prepared, and the structural characteristics were determined by FT-IR, (1)H and (13)C NMR, MALDITOF-MS and element analysis. The corresponding stationary phase (CSP) was used in HPLC and the enantioseparation performance was investigated using chiral 1-phenyl-2-nitroethanol derivatives as test samples in the reverse-phase mode composed of methanol/water and acetonitrile/TEAA. Better separation abilities and excellent enantioselectivities (alpha>1.26, R(S)>1.73) were obtained on MDHB-beta-CD CSP for these chiral compounds in the methanol/water mobile phase. PMID- 22063567 TI - A review of the growth, and of the carcass and meat quality characteristics of the one-humped camel (Camelus dromedaries). AB - The dromedary camel is a good source of meat especially in areas where the climate adversely affects the performance of other meat animals. This is because of its unique physiological characteristics, including a great tolerance to high temperatures, solar radiation, water scarcity, rough topography and poor vegetation. The average birth weight of camels is about 35kg, but it varies widely between regions, breeds and within the same breed. The meat producing ability of camels is limited by modest growth rates (500g/day). However, camels are mostly produced under traditional extensive systems on poor levels of nutrition and are mostly slaughtered at older ages after a career in work, racing or milk production. Camels reach live weights of about 650kg at 7-8 years of age, and produce carcass weights ranging from 125 to 400kg with dressing-out percentage values from 55% to 70%. Camel carcasses contain about 57% muscle, 26% bone and 17% fat with fore halves (cranial to rib 13) significantly heavier than the hind halves. Camel lean meat contains about 78% water, 19% protein, 3% fat, and 1.2% ash with a small amount of intramuscular fat, which renders it a healthy food for humans. Camel meat has been described as raspberry red to dark brown in colour and the fat of the camel meat is white. Camel meat is similar in taste and texture to beef. The amino acid and mineral contents of camel meat are often higher than beef, probably due to lower intramuscular fat levels. Recently, camel meat has been processed into burgers, patties, sausages and shawarma to add value. Future research efforts need to focus on exploiting the potential of the camel as a source of meat through multidisplinary research into efficient production systems, and improved meat technology and marketing. PMID- 22063568 TI - A review of the nutritional content and technological parameters of indigenous sources of meat in South America. AB - Meat yields, proximate compositions, fatty acids compositions and technological parameters are reviewed for species which might be further developed as indigenous sources of meat in South America. These include the alpaca (Lama pacos), capybara (Hydrochoerus hydrochaeris), guanaco (Lama guanicoe), llama (Lama glama), nutria (Myocastor coypus), collared peccary (Tayassu tajacu), greater rhea (Rhea americana), lesser rhea (Rhea pennata), yacare (Caiman crocodilus yacare), tegu lizard (Tupinambis merianae) and green iguana (Iguana iguana). PMID- 22063569 TI - Effects of aging time and natural antioxidants on the color, lipid oxidation and volatiles of irradiated ground beef. AB - Beef rounds aged for one, two, or three weeks after slaughtering were ground added with 0.05% ascorbic acid+0.01% alpha-tocopherol or 0.05% ascorbic acid+0.01% alpha-tocopherol+0.01% sesamol, placed on Styrofoam trays and wrapped with oxygen-permeable plastic film, and treated with electron beam irradiation at 0 or 2.5kGy. The meat samples were displayed under fluorescent light for 7d at 4 degrees C. Color, lipid oxidation, volatile analysis, oxidation-reduction potential (ORP) and carbon monoxide (CO) production were determined at 0, 3, and 7d of storage. Irradiation increased lipid oxidation of ground beef regardless of their aging time and storage period. As aging time increased lipid oxidation increased. Adding sesamol increased the effectiveness of ascorbate and tocopherol combination in reducing lipid oxidation especially as aging and storage time increased. The redness of beef were decreased by irradiation and adding ascorbic acid and alpha-tocopherol before irradiation was effective in maintaining the redness of irradiated ground beef over the storage period. The combination of ascorbic acid+alpha-tocopherol to ground beef was more effective in reducing ORP than adding sesamol. Irradiation increased CO production from all ground beef regardless of aging time or additives treatments. Volatile sulfur compounds produced by irradiation at Day 0 disappeared over the storage period. Alcohol greatly increased in all nonirradiated beef, but volatiles aldehydes only in irradiated control beef. Antioxidant treatments were effective in reducing aldehydes in ground beef during storage. PMID- 22063570 TI - Influence of vacuum-aging period on bloom development of the beef gluteus medius from top sirloin butts. AB - The gluteus medius (GM) from USDA Select beef carcasses was used to test the effect of aging period on bloom development. Top sirloin butts (IMPS #184) were randomly allocated to 0, 7, 14, 21, 28, and 35d vacuum-aging at 2 degrees C (n=10/aging period). Each week, aged top sirloin butts were faced before two 2.5 cm-thick, non-adjacent steaks were cut and instrumental color (L(*), a(*), and b(*)) of the GM was measured at 10-min intervals for 2h after cutting. Steaks aged for 7 and 14d were a more vivid (greater chroma values; P<0.05), redder (greater a(*) values; P<0.05), and more yellow (greater b(*) values; P<0.05) color than steaks from the other aging periods. Change in total color (DeltaE) was greater (P<0.05) for steaks from top sirloin butts aged 7, 14, and 21d than steaks from top butts aged 28 and 35d, whereas oxymyoglobin percentages for steaks from top butts aged 7 and 14 days were greater (P<0.05) than those from top sirloin butts aged 28 and 35d. As much as 90% of the total increase (P<0.05) in a(*), b(*), and chroma values, as well as hue angles and oxymyoglobin percentages, was achieved during the first 60min after cutting. PMID- 22063571 TI - Characteristics of meat emulsion systems as influenced by different levels of lemon albedo. AB - The effect of the addition of lemon albedo on the functional properties of emulsions was studied by using a model system. Oil/water (O/W) model emulsion systems were prepared by the addition of two types of lemon albedo (raw and dehydrated) at five concentrations (0.0%, 2.5%, 5.0%, 7.5% and 10%) to mechanically deboned chicken meat. The emulsion capacity, stability, viscosity and flow properties of the prepared model emulsions were analyzed. In addition, the colour parameters of cooked emulsion gel were determined. The addition of lemon albedo increased the emulsion capacity (EC) and the highest EC value was reached with 5% of albedo added. However, further increase in the albedo concentration caused an inverse trend in the EC values. A similar trend was observed in the emulsion stability (ES) values. Dehydrated albedo (DA) addition caused higher EC and ES values than did raw albedo (RA). DA increased the L(*), a(*) and b(*) values of the cooked emulsion gels. Emulsion viscosity (EV) values were positively correlated with an increase in albedo concentration and the highest EV value was obtained from the emulsions with 10% albedo. Albedo addition did not change the flow properties of the emulsions and, in addition, increased the pseudoplasticity. As a consequence, the use of lemon albedo might be a potential dietary fiber source to enhance the functional and technological properties for frankfurter-type meat products. PMID- 22063572 TI - Effect of full-fat soy paste and textured soy granules on quality and shelf-life of goat meat nuggets in frozen storage. AB - Goat meat nuggets were prepared using commercially available textured soy granules and reduced beany flavour full-fat soy paste (FFSP) made by simple processing technology to compare the performance of these proteins in a comminuted meat system. Addition of soy proteins (soy paste and soy granules) did not significantly affect the product yield, pH, moisture and fat percentage whereas protein content and water holding capacity (% expressible water) were significantly (p>0.05) lower in nuggets with 15% soy paste. Lower force was required to compress or shear the sample as hardness, springiness, gumminess and chewiness decreased in soy paste incorporated nuggets. Soy proteins either paste or granules, did not affect sensory attributes except flavour and overall acceptability. Nuggets with soy paste and control ones did not differ significantly for flavour and overall acceptability whereas nuggets with soy granules were rated significantly (p>0.05) lower. The nuggets remained stable with minor changes in physico-chemical, microbiological and sensory quality during frozen storage (-18+/-1 degrees C) for 90days. It is concluded from this study that FFSP could be successfully incorporated in comminuted meat systems for producing quality products similar to commercially available soy granules. PMID- 22063573 TI - The effect of heat stress on thyroid hormone response and meat quality in turkeys of two genetic lines. AB - The current study evaluated the effect of heat stress on thyroid hormone (T(3) and T(4)) response and meat quality traits in two turkey lines: a growth-selected commercial line and a genetically unimproved control line. Birds were subjected to heat stress for different durations before harvest. Commercial line had higher pH(15min), and lightness values, but lower cook loss and marinade uptake than control line during the heat stress. There was no difference in drip loss between the two lines. The T(3) concentration was positively correlated with cook loss and was negatively correlated with marinade uptake. The thyroid hormone response during heat stress was less stable in the commercial line than in the control line and the unstable thyroid hormone response in commercial turkeys caused by heat exposure might influence the consistency of meat quality. Results of this study may provide an application in selecting turkeys which yield consistent meat quality. PMID- 22063574 TI - Lipid composition of meat and backfat from Casertana purebred and crossbred pigs reared outdoors. AB - The study aimed to evaluate, with regard to the human nutrition, the lipid profile of meat and backfat from gilts and barrows of the Italian autochthonous genotype Casertana and its crossbreed (Casertana*Large White) slaughtered at two different live weights. Meat from the Casertana cross was nutritionally comparable to that from the purebreed and both would be considered healthy, irrespective of sex and weight, due to the relatively low levels of intramuscular lipids and cholesterol. Muscle cholesterol was considerably lower in the heavy pigs than in the light ones and, as weight increased, cholesterol decreased but only in gilts. Females supply meat with higher polyunsaturated fatty acids (PUFA) and slightly lower saturated fatty acids (SFA) respect to barrows and, thus, higher PUFA/SFA ratio. Casertana crossbreds can represent a good alternative to pure Casertana, mainly in the production of Colonnata lard, due to the better fatty acid profile of the subcutaneous adipose tissue. From the nutritional point of view, the optimal slaughtering weight was about 150kg for both genotypes. Heavy pigs, compared to the light ones, produced loin with lower atherogenic and thrombogenic indexes, lower SFA/unsaturated fatty acids ratio, and higher PUFA/SFA ratio. PMID- 22063575 TI - Role of secondary structures in the gelation of porcine myosin at different pH values. AB - Secondary structures, gelation properties and their relationships in porcine myosin were studied by circular dichroism, dynamic rheological measurement and scanning electron microscopy. Gelling of porcine myosin involved a change in myosin conformation with protein-protein and protein-water interactions. The gelation properties were strongly pH and temperature dependent. Near the pI (pH 5.5 and 6.0), porcine myosin could spontaneously coagulate at 15 degrees C resulting partially from the presence of more beta-sheets. Myosin at pH6.5-9.0 began to form a gel at temperatures greater than 38 degrees C. Heating caused alpha-helices to partially turn into beta-sheets and random coils. Subsequently, myosin aggregated and formed a gel network. The gel strength decreased and the water-holding capacity (WHC) increased with increasing pH. Correlation analysis indicated that both the unfolding of alpha-helices and the formation of beta sheets favored the gelation of porcine myosin. A high beta-sheet fraction prior to heating resulted in a low WHC of resultant gel. A compact and uniform gel was also obtained at pH6.5. PMID- 22063576 TI - Enhancing the antilisterial effect of Lactobacillus curvatus CWBI-B28 in pork meat and cocultures by limiting bacteriocin degradation. AB - This work focused on Listeria monocytogenes growth inhibition and growth rebound in raw and cooked pork meat inoculated with Lactobacillus curvatus strains. During storage of raw meat homogenates in the presence of the bacteriocin producing strain Lactobacillus curvatus CWBI-B28wt, the Listeria monocytogenes cfu count was initially reduced to an undetectable level, but a growth rebound occurred after two weeks, coinciding with loss of 70% of the bacteriocin activity present at the end of week 2. The Listeria growth rebound was suppressed when proteolysis of bacteriocin was countered by the absence of proteases (bacteriocin addition to cooked meat) or the presence of 1% soy flour (added to provide competing substrates). Further experiments confirmed that bacteriocin is sensitive to the action of proteolytic enzymes isolated from both Lactobacillus curvatus CWBI-B28wt and the meat matrix. Bacteriocin proteolysis thus emerges as a cause of Listeria growth rebound. PMID- 22063577 TI - Modelling the yield and texture of comminuted pork products using color and temperature. Effect of fat/lean ratio and starch. AB - Practices to control the processing of finely comminuted meat products are proposed. The objective was to test the practical value of both temperature and light reflection measurements made during emulsification as potential indicators of cooking losses and resulting gel texture in pork sausages emulsified within a wide range of temperatures and starch and fat levels. Prior to cooking, pork batters were chopped for different times to ensure final emulsion temperatures ranging from 5 to 50 degrees C. The effects of the fat/lean ratio (0.25 and 0.67) and starch addition (0.8 and 3.2% w:w) on temperature and optical reflection were also investigated. The chopping increased the temperature and decreased the light reflection of fresh meat emulsion. There was no relevant loss of emulsifying capacity at emulsion temperature below 30 degrees C and lightness values over 70 CIE units. The losses and textural parameters of cooked emulsions could be predicted by means of non-linear regression equations based on the temperature and color of the raw emulsion. The determination coefficients obtained ranged from 0.89 to 0.99. The prediction models needed to be fitted to each batter formulation, especially in the presence of reduced levels of gelation agents (meat protein and starch). Lightness was a better predictor than chromaticity, since it decreased constantly with chopping in the range of final emulsion temperatures studied (5-50 degrees C). This confirms previous studies that lightness could be used for monitoring emulsion stability in meat batters. PMID- 22063578 TI - Rapid differentiation of lactic acid bacteria from autochthonous fermentation of Iberian dry-fermented sausages. AB - The populations of lactic acid bacteria (LAB) in different types of Iberian dry fermented sausages from central-west Spain were identified. A simple and rapid electrophoretic method of whole-cell protein profiles was evaluated, correlating it with 16S rRNA gene sequence analysis and biochemical identification by API 50 CHL. A total of 96 isolates were identified by SDS-PAGE showing stable profiles corresponding to 30-45 polypeptides in the range 95-8kDa that were clearly different for the different species and were grouped with those of the 9 reference strains used in this study. The SDS-PAGE method showed that the predominant species were Pediococcus acidilactici (48%) followed by Lactobacillus plantarum (23%) and Lactobacillus brevis (18%). The identifications obtained by this approach were confirmed by sequencing the V2-V3 region of the 16S rRNA gene and by a BLAST search of the GenBank database. However, biochemical identifications by API 50 CHL showed different errors at the genus and species level. In sum, the SDS-PAGE analysis showed itself to be a rapid and accurate differentiation method for the most commonly encountered LAB isolates in dry fermented sausages. PMID- 22063579 TI - Influence of finishing systems on hydrophilic and lipophilic oxygen radical absorbance capacity (ORAC) in beef. AB - The aim of this research was to: (1) develop a reliable extraction procedure and assay to determine antioxidant activity in meat products, and (2) assess the effect of beef finishing system (forage-finished: alfalfa, pearl millet or mixed pastures vs. concentrate-finished) on longissimus muscle antioxidant activity. The effect of extraction method (ethanol concentration and extraction time), protein removal, and sample preparation method (pulverization or freeze drying) were first evaluated to develop an antioxidant assay for meat products. Beef extracts prepared with low ethanol concentrations (20%) demonstrated higher hydrophilic ORAC. Protein removal prior to extraction reduced hydrophilic ORAC values. Sample preparation method influenced both hydrophilic and lipophilic ORAC, with pulverized samples containing higher hydrophilic and lipophilic ORAC values. Beef cattle finishing system (Forage: alfalfa, pearl millet, or natural pasture vs. concentrates) had little impact on muscle hydrophilic ORAC, but muscle from forage finished beef contained greater lipophilic ORAC. In addition, broiling of steaks reduced hydrophilic ORAC. PMID- 22063580 TI - Enrichment of dry-cured ham with alpha-linolenic acid and alpha-tocopherol by the use of linseed oil and alpha-tocopheryl acetate in pig diets. AB - The use of alpha-linolenic acid and alpha-tocopherol enriched pork on the fatty acids and the sensory characteristics of Spanish dry-cured hams have been studied. Five batches of hams were manufactured using the posterior legs of pigs fed on diets with the same ingredients except for the oil source: sunflower (C), linseed (L) or linseed and olive (1/1, w/w, LO). Two different alpha-tocopheryl acetate concentrations [20 (C, L and LO) or 220 (LOE and LE)mg/kg diet] were used. Biceps femoris and Semitendinosus/Semimembranosus muscles from hams with low polyunsaturated fatty acid n-6/n-3 ratio (less than 3) were obtained from animals fed on linseed and linseed/olive oil enriched diets. However, hams from animals fed on diets added with linseed and alpha-tocopheryl acetate (20mg/kg diet) (batch L) were rejected by consumers because of less acceptable sensory characteristics and higher TBARs. The remaining hams had satisfactory sensory and nutritional characteristics. PMID- 22063581 TI - Effect of oat's soluble fibre (beta-glucan) as a fat replacer on physical, chemical, microbiological and sensory properties of low-fat beef patties. AB - This study evaluated the effect of adding oat fibre source of beta-glucan (13.45%) on physical, chemical, microbiological and sensory traits of low-fat (<10%) beef patties as compared to 20% fat control patties. Significant (p<0.05) improvements in cooking yield (74.19%), and retentions of fat (79.74%) and moisture (48.41%) of low-fat patties were attributed to the water binding ability of beta-glucan. Because of larger water retentions moisture contents of raw and cooked low-fat patties were higher (p<0.05) than those of the control patties. Cholesterol content was similar across formulations. Low-fat and control beef patties remained stable in microbiological quality during 60days frozen storage. Low-fat patties were found to be of lower degree of likeness in the taste but juicer than control (p<0.05). Besides appearance, tenderness and colour were not affected by the addition of oat's soluble fibre. Oat fibre can be used successfully as a fat substitute in low-fat beef patties. PMID- 22063582 TI - Evaluation of cholesterol and lipid oxidation in raw and cooked minced beef stored under oxygen-enriched atmosphere. AB - Oxygen-enriched modified atmosphere packaging (MAP) represents an important means to stabilize meat colour but may lead to an increase in lipid oxidation, influencing the acceptability and safety of the product. In this work, the effect on cholesterol and lipid susceptibility to oxidation was investigated in commercial minced beef held under MAP (80% O(2)/20% CO(2)). Cholesterol oxidation products (COPs), peroxide value (PV) and thiobarbituric acid reactive substances (TBARS) were determined, before and after pan frying, at 1, 8 and 15 days since packaging under refrigerated storage (3-4 degrees C). 7alpha-Hydroxycholesterol, 7beta-hydroxycholesterol and 7-ketocholesterol were the more abundant COPs identified. COPs significantly increased in raw beef during storage: after 1, 8 and 15 days since packaging COPs were at the levels of 10.4, 30.7 and 60.5MUg/g of fat, respectively. Cooking did not affect cholesterol oxidation in freshly packaged minced beef but led to a rise in COPs amount with respect to raw muscle after 8 and 15 days of storage. The trend in cholesterol oxidation reflected the progressive increase in lipid peroxidation rate brought by MAP conditions. PMID- 22063583 TI - Relationships of fat-tail dimensions with fat-tail weight and carcass characteristics at different slaughter weights of Torki-Ghashghaii sheep. AB - The purpose of this research was to investigate the relationship between fat-tail and carcass attributes in Torki-Ghashghaii sheep. Thirty ram lambs belonging to six weight groups (weighing from 25 to 50kg) were used. Fat-tail measurements were recorded on the live animals before slaughter. Hot and cold (after 24h in the cold room) carcass weights, and the weights of the tail and internal organs were recorded. The carcass was dissected into conventional cuts. Each cut was de boned and the physically separable fat was removed from the meat. The bone, physical fat and trimmed meat were weighed separately. The weight of trimmed meat as a percentage of slaughter weight did not change significantly from 25 to 50kg live weights (23.4-25.3%). The weights of physically separated fat and the fat tail as a percentage of live weight varied from 6.6% to 15.5% for various weight groups. The correlation coefficients between the tail weight and dimensions were large, positive, and significant. The highest correlation coefficient was found between the tail weight and upper circumference (r=0.88), and the lowest one was found between the tail weight and upper thickness (r=0.61). The upper and lower circumferences of the tail accounted for 85% of the total variation in the tail weight. The tail weight was positively correlated with the meat chemically determined fat (ether extract; r=0.43; P<0.05) and with the total body fat (r=0.70; P<0.01). Further studies are needed to see whether inclusion of fat-tail measurements in breeding programs would result in a decrease in body fat in this breed. PMID- 22063584 TI - Tensile properties of cooked meat sausages and their correlation with texture profile analysis (TPA) parameters and physico-chemical characteristics. AB - The possibilities of using breaking strength (BS) and energy to fracture (EF) for monitoring textural properties of some cooked meat sausages (chopped, mortadella and galantines) were studied. Texture profile analysis (TPA), folding test and physico-chemical measurements were also performed. Principal component analysis enabled these meat products to be grouped into three textural profiles which showed significant (p<0.05) differences mainly for BS, hardness, adhesiveness and cohesiveness. Multivariate analysis indicated that BS, EF and TPA parameters were correlated (p<0.05) for every individual meat product (chopped, mortadella and galantines) and all products together. On the basis of these results, TPA parameters could be used for constructing regression models to predict BS. The resulting regression model for all cooked meat products was BS= 0.160+6.600*cohesiveness-1.255*adhesiveness+0.048*hardness-506.31*springiness (R(2)=0.745, p<0.00005). Simple linear regression analysis showed significant coefficients of determination between BS (R(2)=0.586, p<0.0001) versus folding test grade (FG) and EF versus FG (R(2)=0.564, p<0.0001). PMID- 22063585 TI - Near-infrared reflectance spectroscopy for predicting chemical, instrumental and sensory quality of beef. AB - The aim of this study was to assess near-infrared reflectance (NIR) spectroscopy as a tool for determining sensory and texture characteristics of beef. Chemical, instrumental, texture and sensory characteristics were predicted by near-infrared reflectance spectroscopy carried out on longissimus dorsi muscle samples from 190 young bulls. The use of first derivative gave best predictions together with NIR spectra, except for myoglobin and water holding capacity, which had an R(2) of prediction of 0.91 and 0.82, respectively, using visible and NIR spectra. Tenderness was the best-predicted variable (R(2)=0.98) demonstrating the potential of NIR spectroscopy in the prediction of sensory variables. Chemical composition variables and Warner-Bratzler shear force were predicted with an R(2) of prediction of around 0.7, but protein was not predicted with accuracy. PMID- 22063586 TI - Influence of wet-aging on bloom development in the longissimus thoracis. AB - The longissimus thoracis (LT) from USDA Select beef carcasses was used to test the effect of aging period (0, 7, 14, 21, 28, or 35d) on bloom development (n=10/aging period). After aging, two 2.54-cm-thick, non-adjacent steaks were cut and instrumental color of the LT was measured at 10-min intervals for 2h. All instrumental color parameters increased (P<0.05) over 40% during the first 10min; however, asymptotic points indicated that color plateaued sometime after 120min. Although aging did not (P?0.05) affect the values where color development plateaued, rate of oxymyoglobin formation tended to be the slowest (P=0.06) in LT steaks aged 7d compared to steaks aged 0, 14, 28 and 35d. Results indicated that as much as 90% of the total increase (P<0.05) in instrumental color and oxymyoglobin percentages was achieved during the first 60min after cutting, but aging period had no impact on bloom development. PMID- 22063587 TI - Effect of kimchi powder level and drying methods on quality characteristics of breakfast sausage. AB - This study was conducted to determine the effect of the addition of kimchi powder on the quality characteristics of meat batter and breakfast sausage. Breakfast sausages were supplemented with freeze dried kimchi powder (FKP) or hot air dried kimchi powder (HKP) at levels of 1% (FKP-1 and HKP-1) or 2% (FKP-2 and HKP-2). The emulsion stability, cooking yield, and apparent viscosity in meat batters improved with increments of kimchi powder (p<0.05). Increased levels of kimchi powder in breakfast sausage decreased the L(*) value, pH, and springiness, and increased the a(*) value, b(*) value, hardness, chewiness, and gumminess (p<0.05). Sensory evaluations indicated that a higher overall acceptability was attained when the kimchi powder was added to breakfast sausage at a level of 2%. PMID- 22063588 TI - Screening of lactic acid bacteria and bifidobacteria for potential probiotic use in Iberian dry fermented sausages. AB - The purpose of this study was to select lactic acid bacteria and bifibobacteria strains as potential probiotic cultures during the processing of Iberian dry fermented sausages. A total of 1000 strains were isolated from Iberian dry fermented sausages (363), and human (337) and pig faeces (300) in different culture media. Around 30% of these strains, mainly isolated from Iberian dry fermented sausages in LAMVAB agar, were pre-selected for testing as potential probiotics by their ability to grow adequately at the pH values and NaCl concentrations of these meat products during the ripening process. Of the in vitro investigations used to predict the survival of a strain in conditions present in the gastro intestinal tract, exposure to pH 2.5 showed itself to be a highly discriminating factor with only 51 out of 312 pre-selected strains resisting adequately after 1.5h of exposure. All acid-resistant isolates identified as lactobacilli originated from human faeces (Lactobacillus casei and Lactobacillus fermentum) and pig faeces (Lactobacillus reuteri, Lactobacillus animalis, Lactobacillus murinus, and Lactobacillus vaginalis). Pediococcus acidilactici strains were isolated from Iberian dry fermented sausages and pig faeces, whereas the greatest number of Enterococcus strains were identified as Enterococcus faecium, with this species being isolated from Iberian dry fermented sausages, and human and pig faeces. Most of these strains are promising probiotic meat culture candidates suitable for Iberian dry fermented sausages. PMID- 22063589 TI - Any link between integrin degradation and water-holding capacity in pork? AB - In order to investigate a possible relationship between integrin degradation and water-holding capacity (WHC), integrin was quantified using western blot, and water mobility and distribution was measured by proton NMR T(2) relaxometry at 24h postmortem in pork (n=30) with a large variation in WHC (drip loss varying from 2.8% to 11.3%). Regression analyses revealed correlation coefficients of r= 0.32 (P=0.08) and r=0.40 (P=0.03) for the correlations between the content of integrin determined by western blot analysis and WHC determined as either drip loss or by NMR, respectively. Water mobility and distribution was also measured in 18 meat samples upon 7 days of aging, which revealed a correlation (r=0.54) between integrin content determined by western blot analysis 24h postmortem and the mobility of the myofibrillar water (T(21) relaxation time) at day 7. In contrast, no correlation could be established between integrin content 24h postmortem and WHC at day 7 determined by NMR as the amount of extramyofibrillar water (T(22) population) (r=-0.01). In conclusion, both visualisation by CLSM and quantification of integrin by western blot analyses of suggested that a strong link between integrin degradation and WHC in pork is questionable, whereas integrin degradation seems to have impact on the succeeding development in the mobility of the myofibrillar water. PMID- 22063590 TI - Relationships between sensory descriptors, consumer acceptability and volatile flavor compounds of American dry-cured ham. AB - The relationships between volatile flavor compounds, sensory descriptors and consumer acceptability were determined for eight commercial American dry-cured hams using external preference and flavor mapping. The majority of consumers preferred (p<0.05) hams that had more intense caramelized, smoky, savory and molasses aromas as well as more intense sweet and savory flavors. Sixteen aroma impact compounds were identified from the headspace volatiles of dry-cured hams. The majority of consumers preferred (p<0.05) hams that were characterized by 4 methyl-2-methoxyphenol (sweet ham), 4-ethyl-2-methoxyphenol (sweet ham), 2 methoxyphenol (smoky, cocoa), 2,6-dimethoxyphenol (smoky ham, savory) and 2 furanmethanol (burnt meat, vitamin). Fourteen percent of consumers preferred (p<0.05) two hams that were characterized by methional (baked potato). Consumer acceptability scores were lower for hams either characterized by methanethiol (sulfur), carbon disulfide (sulfur), 2-butanone (sweet), 3-methylbutanal (malty, fermented), 2-heptanone (burnt meat, vitamin), hexanal (cut grass), benzeneacetaldehyde (floral), 1-octen-3-ol (mushroom) or characterized by benzaldehyde (burnt meat, cooked meat) and limonene (citrus). This study revealed how relationships between sensory descriptors, consumer acceptability and volatile flavor compounds could be determined using external preference mapping and used to comprehend the nature of dry-cured ham flavor as it is perceived by a consumer panel. PMID- 22063591 TI - Immersion vacuum cooling of cooked beef - Safety and process considerations regarding beef joint size. AB - Cooked beef samples (1, 2, and 3kg; 4.7, 5.6, and 6.2cm average radius, respectively) were cooled from ~72 to 4 degrees C core temperature using either air blast (AB), immersion vacuum (IVC) or vacuum (VC) cooling. IVC cooled larger samples within 4h and took less than 2.5h between 72 and 10 degrees C. IVC cooling times were on average shorter than AB and longer than VC for all sizes. Differences increased with size. IVC and AB cooling losses were comparable (P>0.05) while lower on average (P<0.05) than VC losses for same size samples. Additionally, samples between 1.0 and 4.3kg (4.2-8.7cm average radius) were cooled by either IVC or VC. Cooling times were between 2.8 and 5.5h for IVC and between 1.1 and 3.2h for VC. There was a significant effect (P<0.01) of sample size on IVC cooling times. Cooling profiles of larger samples were tested using USDA cooling growth model for Clostridium perfringens in beef broth. According to the model, none of the analyzed profiles would support significant growth of the bacteria. PMID- 22063592 TI - The roles of pH extraction and colloidal protein solubility in the optimization of spectrophotometric nitrite determination in meat products via response surface methodology. AB - The influence of four critical factors such as sample weight/borax reagent ratio (B(R) factor), ascorbic acid content (A(R) factor), neutralization with HCl 1N (N(R) factor) and stirring extraction time (S(ET) factor), was investigate in order to find the best conditions (optimization) to develop the official ISO 2.918 spectrophotometric method to determine the residual nitrite content in meat products, using the response surface methodology (RSM) as optimization tool. The factors most strongly affecting nitrite determination in meat products are B(R), N(R) and A(R), due to their respective effects on pH extraction parameters and on the amount of colloidal protein present in the sample extract. At pH?6, for example, the extract - though appearing clear and transparent to the analyst - contains a considerable amount of hydrolyzed protein, which will severely interfere with measurements, generating false-positive results. The colloidal protein present in the extract (?20mg/g, corresponding in these working conditions to an OD(340) value of ?0.600) will lead to the recording of nitrite values greater than those actually present in the sample. In order to avoid these drawbacks, this paper proposes that the amount of borax added (B(R)) varies as a function of sample weight (W(S)), using the ratio W(S)/B(R)=1.11. In order to monitor the analytical method, it is further recommended that pH be adjusted to 6 7 (lower protein solubility) and that colloidal protein levels be ?20mg/g, as confirmed by an OD(340) value of ?0.600. PMID- 22063593 TI - Effects of feeding strategies including different proportion of pasture and concentrate, on carcass and meat quality traits in Uruguayan steers. AB - Eighty four steers were randomly assigned to three pasture treatments with increasing levels of grain (T1: 0%; T2: 0.6%; T3: 1.2% of live weight) and to an ad libitum concentrate treatment, T4, to study the effects on carcass and meat quality. Animals were slaughtered with 500 kg of average live weight per treatment. Average daily gain increased with increasing levels of energy, determining different slaughter dates. Intermediate treatments showed higher carcass weight than T1. T4 and T3 had a higher weight of valuable cuts than T1 and T4. Pistolas from T4 had a higher fat proportion and lower bone percentage. Increasing levels of energy in diet decreased fat yellowness. After 20 days of aging, T4 had the lowest muscle a(*) values and shear force was higher for T4 than for T1. With pastures finishing strategy, no adverse effects on meat quality were detected and tenderness was enhanced. PMID- 22063594 TI - Evidence for post-mortem m-calpain autolysis in porcine muscle. AB - The objective of the present work was to characterize changes in calpain activity in pork post-mortem. Samples from pig M. longissimus dorsi and M. semimembranosus were collected three days post-mortem from 75 animals and analyzed with casein zymography. The results indicated post-mortem autolysis of m-calpain as two m calpain bands were observed on the zymogram gel. Use of M. longissimus dorsi from three pigs collected at different times during storage further confirmed post mortem autolysis of m-calpain. The activity of the autolyzed form of m-calpain was detectable at day 3 and further increased at day 6. The results also showed a decrease in the non-autolyzed m-calpain activity during post-mortem storage. Collectively, these results suggest that m-calpain is active post-mortem in porcine muscles. PMID- 22063595 TI - Effect of fat score on the quality of various meat products. AB - In the larger Swiss abattoirs the fat score (FS) is determined by default as an indicator of fat quality. The FS refers to the iodine number and is related to the degree of unsaturation of the outer layer of backfat. In a feeding trial with Large White gilts, the FS was determined in 47 carcasses. Meat and fat tissues were prepared for the production of salami (SAL), raw-cured bacon (RCB), pork hamburger (PHB) and Vienna sausage (VIS). In the different meat products, the FS was closely related to the percentage of saturated (SFA: r=-0.49 to -0.79) and polyunsaturated fatty acids (PUFA, r=0.36 to 0.79) for RCB, SAL and PHB (p?0.05), but not for VIS. For RCB, significant correlations with FS were seen for the meat:fat-ratio (r=0.39), fat firmness (r=-0.31) and one fat oxidation marker (1 octen-3-ol: r=0.51). The texture (r=-0.60), a(w)-value (r=0.63) and one fat oxidation marker (1-octen-3-ol: r=0.46) were significantly correlated with FS in SAL. On the whole, only a few variables correlated significantly with FS for SAL and RCB and the corresponding relationships were always linear. No significant correlation between FS and any of the technological and sensorial parameters were found for VIS or PHB. PMID- 22063596 TI - Effect of pork lard content on the chemical, microbiological and sensory properties of a typical fermented meat product (Pitina) obtained from Alpagota sheep. AB - The aim was to investigate the physicochemical, microbiological and sensory properties of Pitina, a typical fermented meat product and evaluate the effect of two levels of pork lard content (Low Fat, LF, 10% vs. High Fat, HF, 30%) on its attributes. HF attained lower pH than LF Pitina, which reached lower water activity. LAB comprised the major flora with substantial counts of micrococci, enterococci and mould and yeast. Gram negative Enterobacteria were recovered as coliforms and faecal coliforms. Listeria monocytogenes was also isolated. The lard level influenced the count of micrococci and some sensory attributes. LF attained higher scores for both hardness and cohesiveness and differed from HF in having a more marked odour of ewe and smoke and sweeter taste. HF had a more pronounced odour and taste of garlic and mould than LF. PMID- 22063597 TI - Investigation of candidate genes for glycolytic potential of porcine skeletal muscle: Association with meat quality and production traits in Italian Large White pigs. AB - The objective of this study was to investigate the association of DNA markers in candidate genes for glycolytic potential on meat quality parameters (pH(1), pH(u), glycogen and lactate content and glycolytic potential of semimembranosus muscle) and estimated breeding values (EBVs) for average daily gain, lean cuts, back fat thickness, ham weight, and feed:gain ratio in 272 Italian Large White pigs. Three mutations in the PRKAG3 gene (T30N, G52S and I199V) were investigated as well as single nucleotide polymorphisms in two other skeletal muscle genes (PGAM2 and PKM2) involved in the glycolytic pathway. Association analysis with the PRKAG3 markers showed significant results (P<0.05) only for pH(1) (I199V, with significant additive effect) and lactate content (T30N), confirming, at least in part, the effects of this gene on meat quality traits. Significant association (P<0.05) was also observed for PGAM2 and ham weight EBV with significant additive and dominance effects. PKM2 was associated with average daily gain, lean cuts (P<0.001), back fat thickness and feed:gain ratio (P<0.05), with significant additive and/or dominance effects on these traits. PKM2 encodes for a key enzyme of the muscle glycolytic pathway and maps on porcine chromosome 7 where other studies have reported important QTL for the same traits. These data might suggest an important function of this gene in the mechanisms that produce the observed effects. The results will be important to evaluate the inclusion of some of these DNA polymorphisms in marker assisted selection programs. PMID- 22063598 TI - Physicochemical characteristics of pork fed palm oil and conjugated linoleic acid supplements. AB - The experiment was conducted to determine chemical and physical characteristics of pork fed palm oil in the diets and with two levels of CLA (0.5% and 1.0%) supplementation. Chemical compositions and CLA contents were analyzed from raw loins and ham portions. Color and shear force values were measured in raw and cooked meats. The pork fed CLA supplements contained higher (P<0.05) moisture, less fat, and lower MUFA:SFA, PUFA:SFA and n-6:n-3 ratios. Fatty acid compositions were noticeably changed in the loin meats when palm oil was supplemented with CLA in the pig diets, but not in the hams. The CLA contents of meats increased (P<0.05) with increasing amounts of CLA in the diets, with the c9,t11 CLA isomer was the highest concentration. The loins from pigs fed CLA supplements had lighter (P<0.05) color while the ham portions showed darker color. Cooked loins from pigs fed CLA supplements gave higher (P<0.05) shear forces compared with that fed palm oil only, while cooked hams had lower forces in spite of higher forces were observed in raw state. PMID- 22063599 TI - Dry versus wet aging of beef: Retail cutting yields and consumer sensory attribute evaluations of steaks from ribeyes, strip loins, and top sirloins from two quality grade groups. AB - Top Choice (n=48) and Select (n=48) paired bone-in ribeye rolls, bone-in strip loins, and boneless top sirloin butts were assigned randomly to one of two aging treatments, dry or wet, and were aged for 14, 21, 28 or 35d. Cutting tests, performed to determine retail yields and processing times, showed dry-aged subprimals had lower total saleable yield percentages and increased processing times compared to wet-aged subprimals. Sensory and Warner-Bratzler shear evaluation was conducted to determine palatability characteristics. For the most part, aging treatment and aging period did not affect consumer sensory attributes. However, ribeye and top loin steaks from the Top Choice quality grade group received higher sensory ratings than their Select counterparts. For top sirloin steaks, no consumer sensory attributes were affected by aging treatment, aging period, or quality grade group. PMID- 22063600 TI - Effects of potential antimicrobial ingredients used to control Listeriamonocytogenes on quality of natural casing frankfurters. AB - Listeriosis concerns have led to increased antimicrobial use; reformulation may affect quality. The objective was to determine the effects of potential antimicrobials on quality of natural casing frankfurters. Eleven treatments were used: no antimicrobials (control); 3.0% sodium lactate and sodium diacetate blend (SL+SD); 1.0%, 2.5%, and 3.5% buffered sodium citrate (SC); 1.0%, 2.5%, and 3.5% buffered sodium citrate and sodium diacetate blend (SC+SD); and 1.0%, 2.5%, and 5.0% whey protein peptides (WP). Trained and consumer panelists analyzed sensory characteristics. Cooking yield was unaffected by treatment (P>0.05). Addition of SC and SC+SD decreased pH (P<0.05). Texture profile analysis was conducted. Hunter color values and growth of aerobic bacteria and lactic acid bacteria were monitored over 15 weeks of storage. No samples reached spoilage. SL+SD 3% caused few changes; WP caused changes perceived as negative; and SC and SC+SD caused changes often perceived as positive. PMID- 22063601 TI - Sarcomere length determination using front-face fluorescence polarization. AB - Tryptophan is the major intrinsic fluorophore in muscle and is a constituent of proteins that have two preferential alignments both parallel and perpendicular to muscle fibre direction. A simple theoretical model and an experimental method based on front-face fluorescence polarization technique for tryptophan fluorescence anisotropy measurements were used for the estimation of post-rigor sarcomere length in beef in the range 1.6-3.4MUm. Fluorescence anisotropy and structure-related model variables displayed changes in cold-shortened samples compared with normal and stretched ones. The anisotropy of contracted samples was lowered by misalignment of fibres in the sample. This method can therefore be used for in-line detection of cold shortening which has meat toughness as a consequence. PMID- 22063602 TI - Intramuscular fatty acid profile of longissimus dorsi and semitendinosus muscle from Pateri goats fed under traditional feeding system of Sindh, Pakistan. AB - The present study was undertaken to assess the intramuscular fatty acid composition of different muscles taken from male Pateri (n=15) goats, reared on naturally grown grasses, leaves and pods of Acacia nilotica and crushed cereal, under traditional way of feeding. Goats were slaughtered with an average weight of 68+/-7kg and age 12+/-1 month. The samples were taken from longissimus dorsi region (between the 12th and 13th rib) and distal region of semitendinosus muscle. Results of total fat content and fatty acids composition does not show significant (P>0.05) variation among muscles investigated. The fatty acid composition of muscles studied were primarily composed of oleic (31.50-33.38%), followed by palmitic acid (19.84-22.05%) and stearic acid (22.25-24.91%) respectively. Muscle tissue in general contained an average 51.13% of saturated fatty acids and 48.87% of unsaturated fatty acids. The mean conjugated linoleic acid was found 0.41%, 0.43% and 0.47% in ribeye and loin portion of longissimus dorsi muscle and distal region of semitendinosus muscle, respectively. PMID- 22063603 TI - Influence of the paprika type on redness loss in red line meat products. AB - Paprika, with its high colourant power (measured in ASTA units), imparts higher initial redness to fresh red sausage and fresh chorizo (red line meat products). This higher degree of redness (measured according to the red-green component, a*, and spectrophotometric colour units) is maintained until the end of the products' shelf life. However, the pasteurization necessary to reduce the microbial load of paprika can cause alterations to its stability. The addition of natural antioxidants to pasteurized paprika (rosemary extract) was seen to maintain the colour levels of meat products throughout their shelf life. Differences in the colour of meat batches elaborated with paprika of different colourant power could be detected by consumers in a hedonistic test, who evaluated the colour positively. PMID- 22063604 TI - Effect of a linseed diet on lipid oxidation, fatty acid composition of muscle, perirenal fat, and raw and cooked rabbit meat. AB - Forty Californian*New Zealand rabbits (1kg initial body weight) were fed a control or a linseed isoenergetic diet containing 30g of extruded linseed/kg. Twenty rabbits for each dietary treatment were slaughtered at 11 weeks of age, at 35 days after the start of the experiment. Feeding the linseed diet increased (P<0.005) the content of 18:2n-3 in muscles, perirenal fat, and raw and cooked meat. The long chain n-3 polyunsaturated fatty acid (PUFA) contents were also increased (P<0.01) in the meat. The linseed diet produced a robust decrease in the n-6/n-3 ratio. Cooking did not alter n-3 PUFA more than saturated fatty acids (SFA) or monounsaturated fatty acids (MUFA). However, n-6 PUFA were altered by cooking. The oxidative stability of Longissimus dorsi was not affected by the linseed diet, even after 300min of forced-oxidation. Inclusion of linseed in rabbit diets is a valid method of improving the nutritional value of rabbit meat. PMID- 22063605 TI - Relationships between sensory and physicochemical measurements in meat of rabbit from three different breeding systems using canonical correlation analysis. AB - Meat from rabbits reared either according to a standard (STAND) or a high quality norm (LABEL) or a low growth breeding (RUSSE) system were submitted to a sensory evaluation and to a large set of physicochemical measurements (weight of retail cuts, colour parameters, ultimate pH, femur flexure test, Warner-Bratzler shear test, water holding capacities and cooking losses). STAND rabbit meat exhibited the most juicy meat in back and in leg (p<0.01). Leg tenderness significantly decreased (p<0.001) in the rank order STAND>LABEL>RUSSE. Canonical correlation analysis showed strong correlations between physicochemical and sensory variables (R(2)=0.73 and 0.68 between the two first pairs of canonical variates). Especially, sensory tenderness and WB shear test variables assessed on raw longissimus muscle (LL) were correlated. Fibrous attribute in back was correlated with cooking loss in LL. When analysed separately only RUSSE rabbits exhibited the same relations between variables as those calculated in whole dataset. PMID- 22063606 TI - Suitability of Norwegian short-tail lambs, Norwegian dairy goats and Cashmere goats for meat production - Carcass, meat, chemical and sensory characteristics. AB - Six female Norwegian lambs (29kg body weight, 8 months old), six castrated Norwegian goats (27kg body weight, 10 months old) and six castrated Cashmere goats (20kg body weight, 8 months old) were used to study the relative potential of Norwegian lambs, Norwegian goats and Cashmere goats for meat production. Animals were fattened on silage and commercial concentrate before slaughter. Lamb meat had 4 % lower (P<0.05) proteins and 13% higher (P<0.05) fat content than goat meats. Moreover, m. longissimus dorsi samples from lambs were less red (a(*)) (P<0.05) and had lower colour intensity (C) and wider hue angle (H) than that from goats. Meat from lambs and Cashmere goats had higher proportions of saturated fatty acids (SFA) (P<0.001), especially stearic acid and lower ones for total unsaturated fatty acids (TUFA) and monounsaturated fatty acids (MUFA) than the meat from Norwegian goats. Sensory panellists scored lamb meat fattier, juicier and more tender than goat meats. Meat from Cashmere goats scored highest (P<0.05) in whiteness, and lowest (P<0.05) in both colour tone and colour intensity. It is concluded that, since C18:0 was the main contributor of SFA in meat from Norwegian lamb and Cashmere goats, meats from them are nutritionally comparable to that from Norwegian goats. However, the higher proportion of SFA in Norwegian lambs and Cashmere goats may increase hardness of fat and being easily solidified upon cooling, may influence meat palatability. PMID- 22063607 TI - Diffusion of NaCl in meat studied by (1)H and (23)Na magnetic resonance imaging. AB - The effect of sodium chloride (NaCl) diffusion into meat was investigated. Proton and sodium magnetic resonance imaging were used to determine the diffusion behaviour of brine (NaCl) in porcine Longissimus dorsi and semitendinosus. NaCl diffusion was visualized through images and diffusion coefficients were determined to be in the range 3-7*10(-10)m(2)s(-1), which is in agreement with values reported in the literature. The diffusion coefficient was found to increase during curing, suggesting microstructural changes in the meat. A supplementary experiment proved that the diffusion behaviour of sodium chloride in regions of meat with connective tissue/fat is distinctive from regions with pure myofilament tissue, as anticipated. Apparent diffusion coefficient (ADC) maps showed that meat microstructures shrunk when cured with 20% (w/w) NaCl brine. ADC across (?) the main muscle fiber direction decreased more than ADC along (||) the main muscle fiber direction. The greater shrinkage in the direction across muscle fibers suggests that the curing induced shrinkage of the transverse structures rather than reduction in longitudinal structures. PMID- 22063608 TI - Physical and sensory characterization and consumer preference of corn and barley fed beef. AB - Steaks from corn-fed and barley-fed beef were characterized by a trained panel, which rated corn-fed beef higher (p<0.05) for tenderness attributes and overall flavor intensity. Canadian consumers preferred (p<0.01) cooked and raw steaks from barley-fed beef, while Mexican consumers showed no preference (p>0.05) for either type of finished beef. Japanese consumers showed a preference (p<0.05) for the appearance of raw barley-fed steaks but a preference for cooked corn-fed steaks (p<0.05). No differences (p>0.05) were observed for Warner-Bratzler shear, marbling scores, cooking losses or Hunter colorimeter values. There was a trend for higher concentrations (p<0.08) of the saturated fatty acids in the barley treatment, but no differences (p>0.10) in mono or polyunsaturated fatty acids. PMID- 22063609 TI - Cholesterol concentration and fatty acid profile of red deer (Cervus elaphus) meat. AB - The effects of gender and age on intramuscular fat (IMF) levels, cholesterol concentration, and fatty acid composition were investigated in the semitendinosus (ST) and triceps brachii (TB) muscles of feral red deer (Cervus elaphus). Six stags of >2years of age, four hinds of 1year, and six calves of 6months were shot in Slovenia. Generally, all parameters measured were influenced by interaction of muscle and treatment group (hinds, stags and calves) at the 5% level or less. In ST muscle, the IMF levels were highest for hinds. In the TB muscle, cholesterol was lower for stags than for hinds and calves. The saturated fatty acids were the highest for stags and the mono-unsaturated fatty acids for hinds. The polyunsaturated fatty acids (PUFAs) were the highest for calves and lowest for hinds. The n-3 PUFAs were the lowest for hinds. In both muscles, the calves had higher n-6 PUFAs than stags and hinds. Only the ST muscle of the hinds contained >1% (1.44%) of the conjugated linoleic acid isomer 18:2cis-9,trans-11, while in the TB of hinds and calves this fatty acid was higher than with stags. We conclude that gender and age of feral red deer influence the IMF content, the cholesterol concentration, and the fatty acid composition of the meat. PMID- 22063610 TI - The influence of ante-mortem treatment on relationship between pH and tenderness of beef. AB - Longissimus lumborum et thoracis muscles from 150 cattle comprising Czech Pied breed bulls and cows were used to investigate the relationship between pH value and beef tenderness as influenced by housing before slaughter and by the hanging mode of carcasses. The pH value was measured in the loin at the end of the slaughter-line (pH(0)) and after cooling of carcasses (pH(24),pH(48)). The texture of raw meat was measured 72h post-mortem by the Warner-Bratzler shear method; the shear force was related to pH. Curvilinear relationships with coefficients of correlation r=0.64 (P<0.05) for bulls individually housed and r=0.83 for bulls housed in groups between the shear force and the pH value 24h p.m. were found with maximal shear force (the most tough meat) in the range of pH(24) from 6.2 to 6.4. Lower correlations (r=0.72 and r=0.54) between pH(24) and meat tenderness were found in the case of cows individually housed and housed in groups, respectively. No significant relationships were found between texture and pH measured at the end of the slaughter-line (r=0.59 for bulls and r=0.65 for cows) and 48h post-mortem (r=0.64 for bulls and r=0.50 for cows). The mode of housing of cattle before slaughter influenced the properties of beef significantly. Meat of bulls housed in groups before slaughter was less tender (the shear force was higher) than meat of bulls individually housed. It could be explained by higher depletion of glycogen before slaughter and thus insufficient pH decline. Generally, the meat of cows was more tender than of bulls irrespective of housing. No significant differences were found between the left and right halves of carcasses. Thus the mode of hanging had no influence on beef tenderness. PMID- 22063611 TI - Determination of glass transition temperature of beef and effects of various cryoprotective agents on some chemical changes. AB - Sucrose (2%), sorbitol (2%), mannitol (2%), gum arabic (0.15%), carrageenan (0.15%) and meat stabilizer (0.5%) were blended with ground beef and stored for 6 months separately at -9 degrees C, -13 degrees C (glass transition temperature (T(g)) of beef determined by Differential Scanning Calorimetry (DSC)) and -18 degrees C. Total volatile basic nitrogen (TVB-N) and Thiobarbituric acid-reactive substances (TBARS) were determined at 1, 3 and 6th months of storage. Cryoprotectants and storage period had a significant effect (P<0.05) on the TVB-N and TBARS values. Although there were no statistically significant differences between storage at -13 degrees C (T(g)) and -18 degrees C, storage at -9 degrees C had different effects on TVB-N and TBARS. PMID- 22063612 TI - Xenobiotic clenbuterol in food producing male pigs: Various tissue residue accumulation on days after withdrawal. AB - Using enzyme-linked immunosorbent assay (ELISA) and liquid chromatography tandem mass spectrometry (LC-MS/MS) the concentrations of clenbuterol (ng/g) were shown to be highest in choroid/pigmented retinal epithelium (choroid/PRE) (499.59+/ 26.36ng/g), followed by hair (fair colored) (207.76+/-86.88ng/g), liver (25.06+/ 16.72ng/g) and kidney (6.88+/-3.52ng/g) after 28 days of oral clenbuterol administration in a growth-promoting dose (10MUg/kg BW, twice daily) to food producing male pigs, with a high correlation coefficient between the two methods for all study matrices (r=0.8800-0.9999). In the liver as an alimentary tissue and regulatory matrix for the control of clenbuterol abuse, the maximal allowed concentration of 0.5ng/g was achieved in liver tissue (0.40+/-0.12ng/g) on day 14 and in the kidney (0.28+/-0.10ng/g) on day 7 after treatment withdrawal. In contrast, the concentration of residual clenbuterol in choroid/PRE (57.49+/ 6.13ng/g) and hair (68.36+/-3.35ng/g) recorded on day 14 of withdrawal was 143- and 170-fold that measured in the liver, with a similar ratio persisting on day 35 of withdrawal (164:1 and 183:1, respectively). These findings indicated a high accumulation potential of clenbuterol residues in the hair and choroid/PRE as compared with the liver and kidney, pointing to the pig choroid/PRE and hair as useful new matrices in the control of clenbuterol abuse as a growth promotant in food production, especially after prolonged withdrawal. PMID- 22063613 TI - Temperature evolution and mass losses during immersion vacuum cooling of cooked beef joints - A finite difference model. AB - A finite difference model was developed to describe and predict the temperature and mass loss evolution in reconstructed beef joints during immersion vacuum cooling. Fast cooling is obtained within beef pores and at beef surface when evaporation in the surrounding liquid is high. The cooling rate diminishes as the vacuum chamber pressure stabilizes and the liquid temperature reaches its lower value. The maximum deviation between measured and calculated temperatures was within 5 degrees C for the beef (core and surface) and within 7 degrees C for the surrounding liquid (measured at the bottom of the container). Absolute differences between predicted and experimental mass losses for the liquid and beef sample were around 2% and 1%, respectively. Mass losses are higher during the first period when evaporation is the main mode of heat transfer. Mechanical agitation in the surrounding liquid is suggested as a way to further reduce cooling times and to prevent uneven cooling. PMID- 22063614 TI - Comparison of fresh beef and camel meat proteolysis during cold storage. AB - The objective of this research was to determine the difference in myofibrillar fragmentation of camel meat and beef during postmortem aging. Semitendinosus muscle was excised at slaughter and muscle pH was measured at 6, 12, 24, 48, and 72h postmortem. Myofibril fragmentation index was measured on 1, 3, 5, and 7 days postmortem. Also, myofibrils isolated from semitendinosus muscles of camel and cattle at 1, 3, 5 and 7 days postmortem storage were analyzed using sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Results showed that the camel semitendinosus muscle had significantly higher myofibril degradation values compared to that in beef which was supported by a difference in troponin-T degradation and appearance of a 30kDa band. Postmortem pH decline of camel meat was significantly slower than that of beef. This study demonstrated that the semitendinosus protease activity of camel meat was superior to that of beef, which may have been due to the difference in pH decline. PMID- 22063615 TI - Ultrasonic and sensory characterization of dry-cured ham fat from Iberian pigs with different genetics and feeding backgrounds. AB - The textural and ultrasonic properties of the subcutaneous fat from five batches of dry-cured hams from animals with different genetics (Iberian, Iberian*Duroc) and type of feeding ("montanera", concentrate feeds with different oleic acid content) were studied and related to the sensory traits (oiliness and brightness) of their biceps femoris muscle. The different genetics and feeding backgrounds found in the batches brought about differences in their ultrasonic velocities (average velocity from 4 to 20 degrees C ranged from 1608 to 1650m/s) and textural parameters (maximum force at 8 degrees C ranged from 11 to 21N). On average, batches with lower textural parameters had lower velocities and higher sensory scores. Ultrasonic measurements were used to carry out a discriminant analysis which allowed 78.3% of the samples to be correctly classified in the batches considered. Therefore, ultrasonic and sensory techniques could be useful in the characterization and differentiation of dry-cured hams from Iberian pigs. PMID- 22063616 TI - Effect of electron-beam irradiation before and after cooking on the chemical properties of beef, pork, and chicken. AB - Ground beef, pork, and chicken thigh meats were irradiated at 0 or 5.0kGy before and after cooking and then stored at -40 degrees C in oxygen permeable bags. The pH, lipid oxidation, volatiles, and carbon monoxide production of the meat were determined at 0 and 6months of storage. The pH values of raw meats from different animal species were different (5.36-6.25) and were significantly increased by cooking, irradiation, and storage (p<0.05). Irradiation had no effect on the TBARS values of ground beef and pork, but significantly increased the TBARS of chicken thigh meat. Cooking, whether it was done before or after irradiation, caused significant increase in TBARS and was most significant in chicken and pork. The numbers of volatiles analyzed by GC/MS were higher in irradiated meats than the non-irradiated ones regardless of meat source. Sulfur-containing compounds were newly produced or increased by irradiation, but dimethyl disulfide and dimethyl trisulfide were not detected in the non-irradiated meats regardless of cooking treatment. Irradiation time, whether done before or after cooking, had little effect on the TBARS, volatiles, and carbon monoxide production in the meat. PMID- 22063617 TI - Effects of soybean oil and linseed oil on fatty acid compositions of muscle lipids and cooked pork flavour. AB - This study was conducted to investigate the effects of dietary oil on the fatty acid compositions of the longissimus and biceps brachii muscles and its effects on cooked muscles flavour. Seventy-two crossbred barrows (Duroc*Landrace*Large White), were blocked by weight and randomly assigned to one of three treatments. The three dietary treatments were: (a) no oil supplement (CON); (b) 3% soybean oil supplement (SO3); (c) 3% linseed oil supplement (LO3). Dietary linseed oil and soybean oil significantly increased the contents of C18:3 and C18:2 in the neutral lipids and phospholipids in both longissimus muscle and biceps brachii muscle, respectively. Aroma compounds analysis indicated only few aroma compounds were affected significantly by dietary oil in both cooked longissimus muscle and biceps brachii muscle. The flavour attributes of cooked longissimus muscle and biceps brachii muscle were not influenced by feeding 3% soybean oil. Feeding 3% linseed oil did not deleteriously affect the flavour of cooked longissimus muscle but cooked biceps brachii muscle from LO3 had significantly lower pork flavour and higher abnormal flavour than CON and SO3. PMID- 22063618 TI - Occurrence and growth of yeasts in processed meat products - Implications for potential spoilage. AB - Spoilage of meat products is in general attributed to bacteria but new processing and storage techniques inhibiting growth of bacteria may provide opportunities for yeasts to dominate the microflora and cause spoilage of the product. With the aim of obtaining a deeper understanding of the potential role of yeast in spoilage of five different processed meat products (bacon, ham, salami and two different liver pates), yeasts were isolated, enumerated and identified during processing, in the final product and in the final product at the end of shelf life. Yeasts were isolated along the bacon production line in numbers up to 4.2 log (CFU/g). Smoking of the bacon reduced the yeast counts to lower than 1.0 log (CFU/g) or non-detectable levels. In general, yeasts were only isolated in low numbers during the production of salami, cooked ham and liver pate. In the final products yeasts were detected in low numbers in a few samples (3 out of 30) samples, 1.0-1.3 log (CFU/g). By the end of storage, yeasts were only detected in 1 out of 25 investigated samples 1.8 log (CFU/g). A combination of phenotypic and genotypic methods was used to identify the yeast microflora present during production of the processed meat products. The yeast microflora was complex with 4-12 different species isolated from the different production sites. In general, Candida zeylanoides, Debaryomyces hansenii and the newly described Candida alimentaria were found to be the dominant yeast species. In addition, three putatively previously undescribed yeast species were isolated. Fourteen isolates, representing seven different species isolated during the production of the processed meat products and one species isolated from spoiled, modified atmosphere packed, sliced ham, were screened for their ability to grow in a meat model substrate under a low oxygen/high carbon-dioxide atmosphere (0.5% O(2), 20% CO(2), 79.5% N(2)) at two different temperatures (5 and 8 degrees C). Eleven out of the tested 14 strains were able to grow in the meat model substrate with C. zeylanoides, D. hansenii, Pichia guilliermondii and Candida sake reaching levels of 10(5)-5*10(6) log (CFU/g), where sensoryical changes appear. PMID- 22063619 TI - Relationships between biochemical characteristics and meat quality of Longissimus thoracis and Semimembranosus muscles in five porcine lines. AB - Five porcine genetic lines which represent a high proportion of European pig production were fully characterized for meat quality parameters and muscle biochemical characteristics (Longissimus thoracis, LT, and Semimembranosus, SM). The line characterisation was based on 100 animals each representing Large White, Landrace, Duroc, Pietrain (Halothane negative) and Meishan (a Meishan/Large White crossbred line) prevalent genetic backgrounds. Different meat quality parameters (pH 45min, pH ultimate, electrical conductivity, and colour measurements), as well as muscle water holding capacity, muscle metabolic and contractile traits, fibre type, size and frequencies were measured and their relationships studied. The main differences in the LT were found between the Meishan and Pietrain genetic lines, in relation to the muscle fibre size (larger in Pietrain). The Duroc line was characterized by the muscle oxidative traits and the Landrace by the high percentage of fast glycolytic fibres. In SM, Duroc and Pietrain were distinguished from Landrace and Meishan according to the metabolic and contractile characteristics of this muscle. Large White tended to lie between the other breeds for many of the traits. The measured muscle characteristics were related to differences in drip loss and marbling values and could thereby influence the eating quality of pork. Overall the results show differences between the genetic lines for a number of muscle traits which could have impact on consumer appeal and eating quality. The present findings should serve to emphasise the importance of including eating quality as a trait in breed selection. PMID- 22063620 TI - An improved microtitre enzyme immunoassay to measure the boar taint steroid 5alpha-androst-16-en-3-one in blood plasma of pigs. AB - Androstenone (5alpha-androst-16-en-3-one) is a volatile steroid which is synthesized in boar testes and stored in high amounts in fat thus leading to an urine-like odor in pork. Whereas microtiter assays (MTA) exist for fat determination, measurement in blood with MTA was not yet possible. The system reported here is based on a specific antiserum and a horse radish peroxidase conjugate as tracer. For coating bovine serum albumin was avoided which otherwise would lead to unspecific binding. Blood plasma was extracted with n-hexane, solvent was evaporated in a vacuum centrifuge and the extract was taken up in buffer with 10% methanol. Assay sensitivity was 2.5pg/well (0.025ng/mL), specificity was confirmed by GC-MS (r=0.96; n=50) and inter- and intraassay variation were 4.9% and 5.9%, respectively. Thus an assay system is available for studies in pig production and in wildlife research due to pheromone activity also in other species. PMID- 22063621 TI - Simultaneous application of microbial transglutaminase and high hydrostatic pressure to improve heat induced gelation of pork plasma. AB - The effects of treating porcine plasma with microbial tranglutaminase (MTGase) under high hydrostatic pressure (HHP) were studied as a means of improving its gel-forming properties when subsequently heated at pH 5.5, near the pH of meats. Plasma containing varying levels of commercial MTGase was pressurized (400MPa, room temperature, pH 7) for different times, and adjusted to pH 5.5 prior to heating to induce gelation. MTGase-treatment under HHP led to greater enhancement of heat-induced plasma gel properties as compared to control samples. The greatest improvements were achieved by pressurising plasma with 43.3U MTGase/g protein for 30min, thereby achieving recoveries of 49% and 63% in fracture force (gel strength) and fracture distance (gel deformability) of the subsequently heat induced gels, respectively, relative to gel properties obtained by heating untreated plasma at physiological conditions (pH 7.5). PMID- 22063622 TI - Is authentication of the geographic origin of poultry meat and dried beef improved by combining multiple trace element and oxygen isotope analysis? AB - Data available on contents of up to 72 different trace elements and the oxygen isotope ratio of 78 poultry breast and 74 dried beef samples were analysed to determine whether the accuracy of the prediction of the geographic origin is improved by combining promising methods. Validation was performed by determining the origin of a smaller sub-group using a statistical model established from the data of the second, larger, sub-group. As expected, the combined data proved useful for the determination of the geographic origin of meat samples. However, combining data did not clearly reduce the percentage of incorrectly classified individual samples compared to the two approaches applied separately. In poultry, cross-validation and validation resulted in 83% and 50% correct classifications, respectively. The corresponding values in dried beef were 73% and 43%. In conclusion, compared to element signature data alone, combining both methods did not improve predictions of origin. PMID- 22063623 TI - Electron microscopy of contractile bands in low voltage electrical stimulation beef. AB - This study was designed to explore the effects of low voltage electrical stimulation and delay chilling on the ultrastructure of beef longissimus muscle. The results showed that 44.9% of sarcomeres in the ES samples had contractile zones, and 16.9% of sarcomeres adjacent to contractile zones were stretched in 100 views of electron microscopy. The ultrastructures of 60.9% of sarcomeres changed when the samples were electrically stimulated and then delay-chilled. Contractile bands play an important role in meat tenderization during postmortem aging. PMID- 22063625 TI - Anion transport by the cochlear motor protein prestin. AB - Prestin is a member of the SLC26 solute carrier family and functions as a motor protein in cochlear outer hair cells. While other SLC26 homologues were demonstrated to transport a wide variety of anions, no electrogenic transport activity has been assigned so far to mammalian prestin. We here use heterologous expression in mammalian cells, patch clamp recordings and measurements of expression levels of individual cells to study anion transport by rat prestin. We demonstrated that cells expressing rat prestin exhibit SCN(-) currents that are proportional to the number of prestin molecules. Variation of the SCN(-) concentration resulted in changes of the current reversal potential that obey the Nernst equation indicating that SCN(-) transport is not stoichiometrically coupled to other anions. Application of external SCN(-) causes large increases of anion currents, but only minor changes in non-linear charge movements suggesting that only a very small percentage of prestin molecules function as SCN(-) transporters under these conditions. Unitary current amplitudes are below the resolution limit of noise analysis and thus much smaller than expected for pore mediated anion transport. A comparison with a non-mammalian prestin from D. rerio - recently shown to function as Cl(-)/SO(4)(2-) antiporter - and an SLC26 anion channel, human SLC26A7, revealed that SCN(-) transport is conserved in these distinct members of the SLC26 family. We conclude that mammalian prestin is capable of mediating electrogenic anion transport and suggest that SLC26 proteins converting membrane voltage oscillations into conformational changes and those functioning as channels or transporters share certain transport capabilities. PMID- 22063626 TI - Ca2+ transients in myenteric glial cells during the colonic migrating motor complex in the isolated murine large intestine. AB - Enteric glia cells (EGCs) form a dense network around myenteric neurons in a ganglia and are likely to have not only a supportive role but may also regulate or be regulated by neural activity. Our aims were to determine if EGCs are activated during the colonic migrating motor complex (CMMC) in the isolated murine colon. Strips of longitudinal muscle were removed and Ca(2+) imaging (Fluo 4) used to study activity in EGCs within myenteric ganglia during CMMCs, followed by post hoc S100 staining to reveal EGCs. The cell bodies of EGCs and their processes formed caps and halos, respectively, around some neighbouring myenteric neurons. Some EGCs (36%), which were largely quiescent between CMMCs, exhibited prolonged tetrodotoxin (TTX; 1 MUm)-sensitive Ca(2+) transients that peaked ~39 s following a mucosal stimulus that generated the CMMC, and often outlasted the CMMC (duration ~23 s). Ca(2+) transients in EGCs often varied in duration within a ganglion; however, the duration of these transients was closely matched by activity in closely apposed nerve varicosities, suggesting EGCs were not only innervated but the effective innervation was localized. Furthermore, all EGCs, even those that were quiescent, responded with robust Ca(2+) transients to KCl, caffeine, nicotine, substance P and GR 64349 (an NK2 agonist), suggesting they were adequately loaded with indicator and that some EGCs may be inhibited by substances released by neighbouring neurons. Intracellular Ca(2+) waves were visualised propagating between closely apposed glia and from glial cell processes to the soma (velocity 12 MUm s(-1)) where they produced an accumulative rise in Ca(2+), suggesting that the soma acts as an integrator of Ca(2+) activity. In conclusion, Ca(2+) transients in EGCs occur secondary to nerve activity; their activation is driven by intrinsic excitatory nerve pathways that generate the CMMC. PMID- 22063627 TI - Human sympathetic outflows to skin and muscle target organs fluctuate concordantly over a wide range of time-varying frequencies. AB - Frequency-domain analyses of simultaneously recorded skin and muscle sympathetic nerve activities may yield unique information on otherwise obscure central processes governing human neural outflows. We used wavelet transform and wavelet phase coherence methods to analyse integrated skin and muscle sympathetic nerve activities and haemodynamic fluctuations, recorded from nine healthy supine young men. We tested two null hypotheses: (1) that human skin and muscle sympathetic nerve activities oscillate congruently; and (2) that whole-body heating affects these neural outflows and their haemodynamic consequences in similar ways. Measurements included peroneal nerve skin and tibial nerve muscle sympathetic activities; the electrocardiogram; finger photoplethysmographic arterial pressure; respiration (controlled at 0.25 Hz, and registered with a nasal thermistor); and skin temperature, sweating, and laser-Doppler skin blood flow. We made recordings at ~27 degrees C, for ~20 min, and then during room temperature increases to ~38 degrees C, over 35 min. We analysed data with a wavelet transform, using the Morlet mother wavelet and wavelet phase coherence, to determine the frequencies and coherences of oscillations over time. At 27 degrees C, skin and muscle nerve activities oscillated coherently, at ever changing frequencies between 0.01 and the cardiac frequency (~1 Hz). Heating significantly augmented oscillations of skin sympathetic nerve activity and skin blood flow, arterial pressure, and R-R intervals, over a wide range of low frequencies, and modestly reduced coordination between skin and muscle sympathetic oscillations. These results suggest that human skin and muscle sympathetic motoneurones are similarly entrained by external influences, including those of arterial baroreceptors, respiration, and other less well defined brainstem oscillators. Our study provides strong support for the existence of multiple, time-varying central sympathetic neural oscillators in human subjects. PMID- 22063628 TI - Diet-induced adaptation of vagal afferent function. AB - Afferent signals from the stomach play an important role in inhibition of food intake during a meal. The gastric hormone ghrelin can influence gastric satiety signalling by altering the sensitivity of gastric vagal afferents. Changes in diet, including food restriction and high fat diet (HFD) alter satiety signalling. We hypothesised that the function of gastric vagal afferent endings are affected by both a period of food restriction and a high fat diet, and that the inhibitory effect of ghrelin on vagal afferents is influenced by the different feeding conditions. We found that both fasting and HFD reduced the responses of gastric vagal tension receptors to distension, but not responses of mucosal receptors to mucosal contact. We traced vagal afferents anterogradely to their terminals in the mucosa where we found they were in close apposition to ghrelin-containing cells. Ghrelin receptor mRNA was expressed in vagal afferent cell bodies of the nodose ganglia, and increased in response to caloric restriction, but decreased in HFD mice. In control mice, ghrelin decreased the sensitivity of tension but not mucosal receptors. After caloric restriction or high fat diet, ghrelin inhibited mucosal receptors, and the inhibition of mechanosensitive tension receptors was enhanced. Therefore, both caloric restriction and HFD decrease mechanosensory vagal afferent signals, and augment the inhibitory effect of ghrelin on vagal afferents, but different mechanisms mediate the short- and longer-term changes. PMID- 22063629 TI - Brain glycogen supercompensation following exhaustive exercise. AB - Brain glycogen localized in astrocytes, a critical energy source for neurons, decreases during prolonged exhaustive exercise with hypoglycaemia. However, it is uncertain whether exhaustive exercise induces glycogen supercompensation in the brain as in skeletal muscle. To explore this question, we exercised adult male rats to exhaustion at moderate intensity (20 m min(-1)) by treadmill, and quantified glycogen levels in several brain loci and skeletal muscles using a high-power (10 kW) microwave irradiation method as a gold standard. Skeletal muscle glycogen was depleted by 82-90% with exhaustive exercise, and supercompensated by 43-46% at 24 h after exercise. Brain glycogen levels decreased by 50-64% with exhaustive exercise, and supercompensated by 29-63% (whole brain 46%, cortex 60%, hippocampus 33%, hypothalamus 29%, cerebellum 63% and brainstem 49%) at 6 h after exercise. The brain glycogen supercompensation rates after exercise positively correlated with their decrease rates during exercise. We also observed that cortical and hippocampal glycogen supercompensation were sustained until 24 h after exercise (long-lasting supercompensation), and their basal glycogen levels increased with 4 weeks of exercise training (60 min day(-1) at 20 m min(-1)). These results support the hypothesis that, like the effect in skeletal muscles, glycogen supercompensation also occurs in the brain following exhaustive exercise, and the extent of supercompensation is dependent on that of glycogen decrease during exercise across brain regions. However, supercompensation in the brain preceded that of skeletal muscles. Further, the long-lasting supercompensation of the cortex and hippocampus is probably a prerequisite for their training adaptation (increased basal levels), probably to meet the increased energy demands of the brain in exercising animals. PMID- 22063630 TI - Assessment of cortical reorganisation for hand function after stroke. AB - Stroke often leads to impairment of hand function. Over the following months a variable amount of recovery can be seen. The evidence from animal and human studies suggests that reorganization rather than repair is the key. Surviving neural networks are important for recovery of function and non-invasive techniques such as functional magnetic resonance imaging allow us to study them in humans. For example, initial attempts to move a paretic limb following stroke are associated with widespread activity within the distributed motor system in both cerebral hemispheres, more so in patients with greater impairment. Disruption of activity in premotor areas using transcranial magnetic stimulation prior to movement can impair motor performance in stroke patients but not in controls suggesting that these new patterns of brain activity can support recovered function. In other words, this reorganisation is functionally relevant. More recently, research has been directed at understanding how surviving brain regions influence one another during movement. This opens the way for functional brain imaging to become a clinically useful tool in rehabilitation. Understanding the dynamic process of systems level reorganization will allow greater understanding of the mechanisms of recovery and potentially improve our ability to deliver effective restorative therapy. PMID- 22063631 TI - Control of firing patterns through modulation of axon initial segment T-type calcium channels. AB - Spontaneously active neurons typically fire either in a regular pattern or in bursts. While much is known about the subcellular location and biophysical properties of conductances that underlie regular spontaneous activity, less is known about those that underlie bursts. Here, we show that T-type Ca(2+) channels localized to the site of action potential initiation in the axon initial segment play a pivotal role in spontaneous burst generation. In auditory brainstem interneurons, axon initial segment Ca(2+) influx is selectively downregulated by dopaminergic signalling. This regulation has marked effects on spontaneous activity, converting the predominant mode of spontaneous activity from bursts to regular spiking. Thus, the axon initial segment is a key site, and dopamine a key regulator, of spontaneous bursting activity. PMID- 22063633 TI - Ultrastructural changes during aging in M. longissimus thoracis from moose and reindeer. AB - Game meat is commonly consumed in Europe but few studies have examined the quality related parameters. In this study we examined the changes in ultrastructure at four times postmortem in M. longissimus from moose (Alces alces) and reindeer (Rangifer tarandus tarandus). The moose were slaughtered during a hunt and reindeer by Swedish standard practices for this semi-domestic animal. Ultrastructural changes occurring in all animals included separation of the sarcolemma from myofibrils, I band breaks, and cytoskeleton breaks; however both I band breaks and cytoskeletal breaks were less common in moose and reindeer than values reported for sheep and beef. Fiber area in the longissimus thoracis muscle was approximately 3270 MUm(2) for moose and 1170 MUm(2) for reindeer indicating that the tenderness of reindeer meat may be largely determined by fiber size. PMID- 22063632 TI - Modulation of Kv3.4 channel N-type inactivation by protein kinase C shapes the action potential in dorsal root ganglion neurons. AB - Fast inactivation of heterologously expressed Kv3.4 channels is dramatically slowed upon phosphorylation of the channel's N-terminal (N-type) inactivation gate by protein kinase C (PKC). However, the presence and physiological importance of this exquisite modulation in excitable tissues were unknown. Here, we employed minimally invasive cell-attached patch-clamping, single-cell qPCR and specific siRNAs to unambiguously demonstrate that fast-inactivating Kv3.4 channels underlie a robust high voltage-activated A-type K(+) current (I(AHV)) in nociceptive dorsal root ganglion neurons from 7-day-old rats. We also show that PKC activation with phorbol 12,13-dibutyrate (PDBu) causes a 4-fold slowing of Kv3.4 channel inactivation and, consequently, accelerates the repolarization of the action potential (AP) by 22%, which shortens the AP duration by 14%. G protein coupled receptor (GPCR) agonists eliminate I(AHV) fast inactivation in a membrane-delimited manner, suggesting a Kv3.4 channel signalling complex. Preincubation of the neurons with the PKC inhibitor bisindolylmaleimide II inhibits the effect of GPCR agonists and PDBu. Furthermore, activation of PKC via GPCR agonists recapitulates the effects of PDBu on the AP. Finally, transfection of the neurons with Kv3.4 siRNA prolongs the AP by 25% and abolishes the GPCR agonist-induced acceleration of the AP repolarization. These results show that Kv3.4 channels help shape the repolarization of the nociceptor AP, and that modulation of Kv3.4 channel N-type inactivation by PKC regulates AP repolarization and duration. We propose that the dramatic modulation of I(AHV) fast inactivation by PKC represents a novel mechanism of neural plasticity with potentially significant implications in the transition from acute to chronic pain. PMID- 22063634 TI - Effects of hot water and lactic acid treatment of beef trimmings prior to grinding on microbial, instrumental color and sensory properties of ground beef during display. AB - The impact of 82 degrees C hot water (HW) or 5% lactic acid (LA) applied aerobically or by vacuum to beef trimmings prior to grinding on Salmonella Typhimurium (ATCC 1769NR; ST), Escherichia coli (ATCC 11775; EC), coliform (CO), aerobic plate count (APC), instrumental color and sensory characteristics of ground beef through simulated retail display was investigated. For this, beef trimmings were inoculated with a mixture (7 log CFU/ml each) of ST and EC, and treated either aerobically or under vacuum in a tumbler with HW or LA antimicrobials. Trimmings were ground, packaged and sampled on days 0, 1, 2, 3 and 7 of display for ST, EC, CO, APC, sensory and instrumental color characteristics. Vacuum HW or LA application had no additive effect (P>0.05) when compared with aerobic application for reducing EC, ST, CO or APC. However, lactic acid was effective for reducing (P<0.05) EC, CO and APC, but reduced ground beef redness. PMID- 22063635 TI - The effect of selected functional additives and heat treatment on nitrosamine content in pasteurized pork ham. AB - The influence of pasteurization and sodium chloride, sodium ascorbate, polyphosphates and sodium nitrite coupled with pasteurization on nitrosamine contents in pork was studied. Nitrosamines: dimethylonitrosamine (DMNA) and diethylonitrosamine (DENA) were extracted from raw material, distilled, condensed in an evaporator under lowered pressure and analyzed chromatographically. An inhibitory effect of NaCl and sodium ascorbate on volatile nitrosamines (DMNA and DENA) was seen. Adding solutions of polyphosphates to the meat caused a slight increase in nitrosamine contents, higher than noted with sodium chloride. The effect of these compounds on nitrosamine formation depended on the presence of polyphosphates and sodium nitrite in the brine. If the brine contained nitrites, the adverse effect of sodium ascorbate and NaCl on nitrosamine formation was weaker. Moreover, a strong inhibitory effect of pasteurization on DMNA and DENA formation was observed. PMID- 22063636 TI - Effects of vascular infusion with a solution of saccharides, sodium chloride, and phosphates with or without vitamin C on carcass traits, Warner-Bratzler shear force, flavor-profile, and descriptive-attribute characteristics of steaks and ground beef from Charolais cattle. AB - Two groups of 18 grain-finished steers were utilized. Nine from one group were infused via the carotid artery immediately after jugular vein exsanguination with an aqueous solution containing saccharides, NaCl, and phosphates (MPSC; MPSC, Inc., Eden Prairie, MN, USA). Nine steers served as non-infused controls (CON). An additional 18 steers were infused with either MPSC (n=9) or MPSC plus 1000 ppm vitamin C (MPSC+C, n=9) solutions. Steers infused with MPSC had higher dressing percentages and organ weights than CON steers. Vascular infusion with MPSC had no effects on USDA yield or quality grade traits, descriptive-attribute sensory panel evaluations, or Warner-Bratzler shear force of longissimus lumborum and semitendinosus muscles. Vascular infusion with MPSC resulted in some significant, but inconsistent effects on flavor-profile characteristics of cooked beef. The addition of vitamin C to the MPSC solution did not provide any benefit. PMID- 22063637 TI - Reduction of E. coli, Salmonella typhimurium, coliforms, aerobic bacteria, and improvement of ground beef color using trisodium phosphate or cetylpyridinium chloride before grinding. AB - The impact of 10% trisodium phosphate (TSP) or 0.5% cetylpyridinium chloride (CPC) applied to beef trimmings either aerobically or under vacuum before grinding on Salmonella typhimurium (ST), Escherichia coli (EC), coliform (CO), aerobic plate count (APC), color and sensory attributes of ground beef through display was studied. For this, beef trimmings were inoculated with ST and EC then treated with either TSP or CPC in vacuum or aerobic conditions. Trimmings were ground, packaged, displayed under simulated retail conditions and sampled on days 0, 1, 2, 3 and 7 for microbial, instrumental color, and sensory color and odor characteristics. Aerobic and vacuum antimicrobial application methods were equally effective (P>0.05) for reducing microorganisms in ground beef. Trisodium phosphate and CPC reduced (P<0.05) all bacterial types monitored. In addition, TSP and CPC improved (P>0.05) ground beef redness (a*), oxymyoglobin stability (630 nm/580 nm) and sensory overall color throughout display without adversely affecting odor characteristics. PMID- 22063638 TI - Lipid traits of muscles as related to genotype and fattening diet in Iberian pigs: total intramuscular lipids and triacylglycerols. AB - Thirty pigs were allotted into four groups according to the fattening diet ("Montanera", diet= acorns and pasture; and "Pienso", diet=concentrated diet) and genotype (Iberian and Iberian*Duroc pigs). Lipid, fatty acid and triacylglycerol compositions,were measured in Biceps femoris muscle. Fattening diet largely affected muscle lipid composition. Total intramuscular lipid and triacylglycerol contents were higher in Montanera pigs than in Pienso pigs (8.0-8.1% vs 6.0-6.8% and 7.4-7.3% vs 6.2-5.4%, respectively). In Montanera pigs, triacylglycerols contained more oleic acid (54.7-56.8% vs 53.5-53.8% and less stearic and palmitic acids (8.8-8.4% vs 9.4-10.2% and 22.2-23.3 vs 23.7-24.4% respectively) and accordingly less PSO and more POL, POO and OOO(?) triacylglycerols compared to Pienso pigs (13.1-13.6% vs 16.2-19.2%, 4.4-3.5% vs 3.0-2.7%, 53.1% vs 51.3-51.9% and 10.1-12.3% vs 8.3-8.6%, respectively). Genotype had no effect on lipid and triacylglycerol contents of muscles and showed only a slight effect on fatty acid and triacylglycerol compositions. PMID- 22063639 TI - Differentiation of cattle species in beef by PCR-RFLP of mitochondrial and satellite DNA. AB - Methods currently used for the identification of the species origin of meat or tissue samples have not been validated for other bovine species than taurine cattle or water buffalo. These methods also do not discriminate between the different bovine species that are used as source of beef. Here, we describe two complementary methods for detection and differentiation of bovine species, which are based on mutations in mitochondrial DNA and centromeric satellite DNA, respectively. The analysis of satellite DNA is especially relevant for the identification of animals that are of hybrid origin. PMID- 22063640 TI - Comparison of shelf life of vacuum-packed pork and beef. AB - The relevance of the intrinsic factors of meat to the sensorial shelf life of vacuum-packed, cold-stored minced pork and beef was investigated. The intrinsic factors studied were the pH and the concentrations of glycogen, glucose, glucose 6-phosphate, l-lactate and fat. The initial bacterial loading was the same on all the meat. High correlations were found between the initial values of pH, fat and l-lactate, respectively, and the rate of spoilage. Using partial least square regression, it was shown that changes in the pH and the concentrations of l lactate and glucose-6-phosphate during storage were able to explain 68% of the variation observed in the rate of spoilage. No relationship was found between spoilage and the origin of the meat (pork or beef). PMID- 22063641 TI - Eating quality of lamb meat: effects of breed, sex, degree of maturity and nutritional management. AB - The eating quality of lamb meat of three indigenous Greek dairy breeds of sheep, reared under different nutritional management conditions, was assessed by Taste Panel Tests (TPT). Lean samples from the leg joints of 69 lamb carcasses of the Boutsko (B), Serres (S) and Karagouniko (K) breed were used. For the first TPT, 24 lambs (four males and four females of each breed) were reared in individual pens on a concentrate ration fed ad libitum. For the second TPT, 27 individual penned male lambs were fed on Lucerne hay ad libitum and on three different levels of concentrate: High (H), Medium, (M) and Low (L). For the third TPT, 18 male lambs were used; initially the groups were fed indoors for 63 days on three different levels of concentrate (H, M and L) together with ad libitum Lucerne hay, and subsequently finished on irrigated, sown pasture. For TPT 1, leg joints were obtained from lambs that had been slaughtered at 30, 45, 60 or 90% of mature weight (PMW) for each breed. For TPT 2, lambs were slaughtered at 23, 28 or 33 kg target slaughter live weights (TSLW), common for all breeds. For TPT 3, lambs were slaughtered at 48 or 55% of PMW for each breed. Panellists assessed warm, roasted lean samples of leg joints and rated Flavour, Juiciness, Tenderness and Overall Acceptability. In TPT 1, degree of maturity significantly affected Flavour, Tenderness and Overall Acceptability whereas sex affected only Flavour. In TPT 2, breed and concentrate level significantly affected the quality characteristics, but concentrate level had no significant effect in TPT 3. Effects associated with slaughter weight were significant for most characteristics in all TPT, with decreasing acceptability for older/heavier lambs. Significant interactions were found between breed and the other factors in TPT 2 and TPT 3 for most quality characteristics. Results from these studies suggest changing traditional production systems may enhance the eating quality of lamb meat. PMID- 22063642 TI - Stunning and slaughter of ostriches. AB - A study of the commercial stunning and slaughter of 783 ostriches in a Republic of South African abattoir revealed that a simple ostrich handling system, combined with a leg clamp applied during stunning current flow and operated by experienced ostrich slaughtermen, resulted in a humane, efficient slaughter process. It was estimated that an electrical stunning current in excess of 400 milliamps at 50 Hz AC, applied to the head only, would prevent recovery in more than 90% of the ostriches, when bled within 60 s from the start of stunning. The identification of rhythmic breathing movements indicate the first stages of recovery and is therefore an essential diagnostic 'tool' in recognising the effectiveness of the stunning treatment. The identification of rhythmic breathing movements in the ostrich after stunning is difficult because spinal reflexes, which produce contraction of limb muscles and result in almost rhythmic body movements could easily be confused with breathing movements. PMID- 22063643 TI - Cooking method and endpoint temperature effects on sensory and color characteristics of pumped pork loin chops. AB - The objective of this study was to evaluate the effects of pumping, cooking method and endpoint temperature on quality of fresh pork chops. The longissimus was removed from 30 paired pork sides. One side was pumped to 110% of original weight (0.4% phosphate, 0.4% salt+added water). Chops were cut (2.5 cm thick) then fried or grilled to 70 or 80 degrees C. As endpoint temperature increased from 70 to 80 degrees C, pork flavor increased (P<0.05) from 95 to 104 (on a 150 point scale) for pumped samples but remained constant in unpumped samples. Juiciness decreased when unpumped samples cooked to 80 degrees C (62) rather than 70 degrees C (78). Warner-Bratzler shear values were lower (P<0.05) in pumped chops than in unpumped controls. Pork flavor was higher and off-flavor was lower in fried chops. Pumping loins appears to enhance sensory attributes of chops even when cooked to abusive endpoint temperatures with limited detrimental effects on physical characteristics. PMID- 22063644 TI - Temperatures and ages of boxed beef packed and distributed in Canada. AB - Boxes of beef were examined when product was packed and when boxes were loaded out of five packing plants, when boxes were loaded into and loaded out of seven refrigerated warehouses, and when boxes were received and opened at 21 retail stores. At each stage of handling at each facility, the boxes to be examined were selected at random. For each selected box, the temperature of product at the centre of the box was measured, and the date of packing and the plant of origin were noted. When cuts were packed, the minimum, median and maximum temperatures were about 2, 6 and 18 degrees C, respectively. Temperatures were successively lower when boxes were loaded out of packing plants, into warehouses and out of warehouses. When loaded out of warehouses, the minimum, median and maximum temperatures were about -2, 1 and 8 degrees C, respectively. The ranges of temperatures were similar, but the median temperatures were about 2 or 1.5 degrees C, respectively, when boxes were received at or were opened at retail stores. At packing plants and warehouses, the temperatures of manufacturing and ground beef were lower than those of cuts, but at the retail store the temperatures of all types of product were similar. When boxes were opened at retail stores, the minimum, median and maximum ages of cuts were about 2, 20 and 130 days, respectively; and the corresponding ages for manufacturing and ground beef were 2, 7 and 56 days, respectively. The data indicate that boxed beef is generally cooled to and maintained at temperatures within the range sought by the meat industry. However, cooling to chiller temperatures of product that is packed while warm can take several days; and some product is held for times that are excessive in view of the temperatures of boxed beef. PMID- 22063645 TI - Muscle lipids, vitamins E and A, and lipid oxidation as affected by diet and RN genotype in female and castrated male Hampshire crossbreed pigs. AB - The objectives of this study were to investigate the polar and neutral lipid fatty acid composition, content of retinol, alpha-tocopherol, gamma-tocopherol and level of oxidation of the pig muscle (M. longissimus dorsi). Female and castrated male Hampshire crossbreeds were produced in two systems. One group was raised indoors with a more polyunsaturated diet and the other raised outdoors with a more saturated diet. The level of polyunsaturated fatty acids in muscle was higher in the indoor females compared with the outdoor females, indoor castrated males and outdoor castrated males. The increased level of polyunsaturated fatty acids in the muscle, which was accompanied by a relatively low content of alpha-tocopherol, increased the susceptibility to lipid oxidation in the form of MDA (malondialdehyde) in the indoor female pigs. Finally, the level of polyunsaturated fatty acids in the polar lipids was affected by the RN genotype, and this difference was dependent on sex. In conclusion, diet has a major effect on the fatty acid composition and oxidation stability in pork muscle, but additional factors such as sex and RN genotype might also contribute. PMID- 22063646 TI - Photooxidation of nitrosylmyoglobin at low oxygen pressure. Quantum yields and reaction stoechiometries. AB - Photooxidation of the nitrite-cured meat pigment, nitrosylmyoglobin, in aqueous solution saturated with a 20% CO(2)/80% N(2) gas mixture with varying oxygen contents (0.1, 0.5 or 1.0%) was found to depend linearly on the oxygen content for both visible (436 nm) and UV-light (366 nm). Quantum yields were similar for the two wavelengths of excitation in agreement with previous findings at higher oxygen pressures. The reaction stoechiometry for photooxidation was different from that of thermal oxidation (investigated at the same oxygen pressures) with a unity MbFe(II)NO/O(2) ratio in the thermal reaction and a ratio larger than one for the photooxidation. For cured meat products packed in modified atmospheres light exposure may be even more harmful for the oxidative stability than expected from the concentration of residual oxygen. PMID- 22063647 TI - Carcass quality in male fallow deer (Dama dama): effects of age and supplementary feeding. AB - Thirty-two male fallow deer, half 18- and half 30-month-old, were slaughtered after a 4-month feeding trial on pasture alone or with daily supplement of 500 g (dry matter) concentrate/head (eight each 18- and 30-month-old). The concentrate was composed of 40% maize, 25% sugar beet pulp, 20% alfalfa, 13% soy flakes, 2% minerals and vitamins. Supplemented deer were heavier (49.9 vs 45.0 kg) and their carcasses produced higher dressing proportions (61.5 vs 57.2%) and bigger amounts of first quality cuts. Supplemented feeding improved muscle development and fat deposition. Thirty-month-olds were heavier than 18-month-olds (53.3 vs 41.6 kg) and their carcasses produced higher dressing proportions (60.9 vs 57.7%) and bigger amounts of first quality cuts; older deer carcasses showed better conformation and bigger amounts of fat deposition. PMID- 22063648 TI - Salivary alpha-amylase and cortisol responsiveness following electrical stimulation stress in major depressive disorder patients. AB - Major depressive disorder (MDD) is often associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis by chronic stress. In comparison, psychosocial stress-induced activation of salivary alpha-amylase (sAA) functions as a marker of sympathoadrenal medullary system (SAM) activity. However, in contrast to salivary cortisol, sAA has been less extensively studied in MDD patients. The present study measured sAA and salivary cortisol levels in patients with MDD. The authors determined Profile of Mood State (POMS) and State-Trait anxiety Inventory (STAI) scores, Heart Rate Variability (HRV), and sAA and salivary cortisol levels in 88 patients with MDD and 41 healthy volunteers following the application of electrical stimulation stress. Patients with major depressive disorder were 8 points or more on Hamilton Depression Scale (HAM-D) scores. Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue, and Confusion scores in patients with major depressive disorder were significantly increased compared to healthy controls. In contrast, Vigor scores in patients with MDD were significantly decreased compared with healthy controls. There was no difference in heart rate variability measures between MDD patients and healthy controls. The threshold of electrical stimulation applied in MDD patients was lower than that in healthy controls. SAA levels in female MDD patients were significantly elevated relative to controls both before and after electrical stimulation. Finally, there were no differences in salivary cortisol levels between major depressive patients and controls. In the present study only three time points were explored. Furthermore, the increased secretion of sAA before and after stimulation could allude to an increased responsiveness of novel and uncontrollable situations in patients with MDD. These preliminary results suggest that sAA might be a useful biological marker of MDD. PMID- 22063649 TI - Associations of DNA markers with meat quality traits in pigs with emphasis on drip loss. AB - Phenotypic information on 1155 market pigs for several pig meat quality traits, was collected. Genotypes on 12 DNA markers, including RYR1 and PRKAG3 I199V, were also obtained on all pigs to investigate the relationship between genetic markers and meat quality. The RYR1 gene had the highest impact on meat quality, however, several other markers showed significant effects on one or more traits. Animals heterozygous at the RYR1 locus were significantly inferior in almost all meat quality traits, except ultimate pH value, initial conductivity and redness of the meat. Drip loss from case-ready meat (measured from 1 to 7 days post-mortem) was 43% higher for heterozygotes than animals of the stress resistant genotype. The homozygous genotype II at position I199V of the PRKAG3 locus also resulted in less drip loss than genotypes IV and VV, regardless of the method and time of measurement. Furthermore, the favourable genotype related to higher ultimate pH and darker meat. Both loci significantly affected the intercept, linear and quadratic terms of fitted drip loss development curves. The favourable genotypes showed a lower drip loss after one day of measurement and a slower increase and a more linear development over time. Whilst the RYR1 and PRKAG3 markers influenced numerous meat quality traits, some of the other markers were also found to have significant effects on one or two meat quality traits. Markers at MC4R and HMGA1 loci significantly affected drip loss, whereas LDHA, CAST (Hpy188I) and ATP2A1 influenced pH value. In addition, the marker ATP2A1 was associated with variation in intramuscular fat content in M. longissimus dorsi. GLUT4 affected temperature 45min post-mortem and several markers (MC4R, LDHA, GLUT4, HMGA1, CAST (Hpy188I and PvuII)) influenced one or two of the different colour measurements. The markers at MC4R, CKM, AGRP, PRKAG3, and HMGA1 loci were tested for their interactions with RYR1 regarding drip loss. Only AGRP showed a significant interaction, but this was based on only a few animals with the homozygous genotype for one allele. Our results suggest that genetic markers provide a useful tool to improve meat quality in pigs independently from RYR1, especially the mutation I199V in the PRKAG3 gene. PMID- 22063650 TI - Application and assessment of extruded edible casings manufactured from pectin and gelatin/sodium alginate blends for use with breakfast pork sausage. AB - Casings formed from pectin (PN) containing 2.5% and 5% corn oil (CO) and olive oil (OO) and gelatine/sodium alginate blends (GSAB) containing 2.5% CO and OO respectively were used for sausage manufacture. Mechanical properties and water content of casings were assessed prior to application. Following sausage manufacture, product quality and shelf-life evaluation were assessed in terms of sensory attributes, instrumental colour, moisture loss and lipid oxidation. All manufactured casings were of good quality and initially produced intact and stable sausage products. However, with time, shrinkage of products occurred where GSAB casings were used. Sensory analysis of sausages showed that PN casings were more preferred to GSAB casings for sausage manufacture. CIE colour analysis supported sensory evaluation. Water losses from sausages using GSAB casings were lower compared to sausages using PN casings due to GSAB casings having higher ability to trap and absorb water compared to PN casings. Lipid oxidation developed over time for all sausage products, however, sausages manufactured using GSAB casings containing both CO and OO at 2.5% had better oxygen barrier properties compared to sausages manufactured using PN containing the same concentration of emulsified oils. Sausages manufactured using casings containing OO were more prone to lipid oxidation than those using CO. Importantly, sausages manufactured using PN casings containing 5.0% CO were extremely stable to lipid oxidation over a six day storage period and significantly, were <1 on the TBARS numbers scale. PMID- 22063651 TI - Mass spectrometric evidence for a zinc-porphyrin complex as the red pigment in dry-cured Iberian and Parma ham. AB - Extracts containing red pigment complexes from the two types of dry-cured hams, Italian Parma and Spanish Iberian ham, were obtained using water and acetone as extraction solvents followed by a crude purification with C18 column filtration. The purified extracts were then analyzed spectroscopically by recording absorption and fluorescence spectra (lambda(ex)=420nm), which both indicate the presence of chemically identical red chromophores with properties similar to a complex of transition metals and protoporphyrin IX. Electrospray ionization mass spectrometry (ESI-MS) in the positive ion mode confirms the presence of identical chemical compounds. ESI-MS in the negative ion mode detects a cluster of seven isotopologue ions (that of m/z 623.2 as the most intense) with a pattern matching that of a Zn protoporphyrin IX complex. Based on mass spectral data it is concluded that a Zn-porphyrin complex constitutes a major chromophore in dry cured Iberian ham as well as in Parma ham. PMID- 22063652 TI - Sensory characteristics of Iberian dry-cured loins: Influence of crossbreeding and rearing system. AB - The sensory characteristics of Iberian dry-cured loins and the influence of crossbreeding (pure Iberian - IB, Iberian female*Duroc male - IB*D and Duroc female*Iberian male - D*IB) and rearing system (outdoors fed on acorns and pasture - MON, indoors fed on concentrates high in oleic acid sunflower oil and supplemented with 250mg/kg of alpha-tocopherol acetate -HOVE- and indoors fed on control concentrates - CON) on sensory attributes were studied. Dry-cured loins from IB-MON and IB-HOVE pigs, which showed the highest intramuscular fat (IMF) content (p<0.01), reached higher scores for brightness, marbling traits (intensity, size and shape) and juiciness, and lower for hardness, dryness and fibrousness than loins from crossbred pigs (IB*D-HOVE, IB*D-CON and D*IB-HOVE). In fact, IMF content was positively linked to juiciness and marbling attributes and negatively to dryness, hardness and fibrousness, which was also observed in the principal component analysis (PCA). Neither the crossbreeding nor the rearing system seemed to influence odour, flavour and taste features. The PCA evidenced that dry-cured loins from IB-MON and IB-HOVE batches gathered together and were placed near to marbling attributes, juiciness and IMF content. PMID- 22063653 TI - An evaluation of simple cleaning methods that may be used in red meat abattoir lairages. AB - Concrete tiles artificially contaminated with field strains of Escherichia coli and Salmonella kedougou, with and without the presence of bovine faecal matter, to simulate visually clean and visually dirty surfaces respectively, were cleaned using a specially designed mechanical rig. Cleaning was carried out using (1) water under mains pressure, (2) water under pressure, (3) water under pressure with a proprietary sanitising agent, (4) steam under pressure and combinations of (5) mains water followed by steam under pressure or (6) water under pressure followed by steam under pressure. Thirty replicates of each of visually clean and visually dirty concrete surfaces were cleaned using each method. Where there was no faecal matter, the use of a proprietary sanitiser at maximum recommended concentration, or the application of steam under pressure gave greater reductions in microbial contamination than the use of mains or a pressure wash. Where the surface was visually contaminated with the faecal material, the use of a pressure wash followed by immediate steam application gave reductions in microbial contamination comparable with the use of a proprietary sanitiser at maximum recommended concentration. The use of steam alone on a visually dirty surface was not an effective means of reducing microbial contamination. A small pilot trial under commercial conditions ranked the efficacy of cleaning treatments as follows: pressure washing followed immediately by steam application was the best method of cleaning a holding pen floor, followed by use of a sanitising agent at the greatest concentration recommended by the manufacturer, and then by pressure washing alone. Pressure washing followed by a delayed steam application appeared to give a poor final result on the surface. PMID- 22063654 TI - Chemical and sensory characterisation of pan-fried pork flavour: Interactions between raw meat quality, ageing and frying temperature. AB - The effect of raw meat quality and cooking temperature on flavour generation in pork was investigated. The semimembranosus muscle was varied through genetics (carrier (HLY) and non-carrier (DLY) of the RN(-) allele) and ageing at 2 degrees C (2, 15, and 22 days), whereas the pan-frying temperatures were 150 degrees C and 250 degrees C. HLY gave more pronounced 'fried' and 'burnt' notes than DLY after frying. This could partly be explained by a significantly higher concentration of glucose and glucose 6-phosphate in HLY after 22 days of ageing. HLY was generally perceived as more sour, which correlated well with the measured pH of HLY, but not to the l-lactate concentration. HLY was furthermore perceived as more tender and juicier than DLY, both attributes increased during ageing. Lipid-derived aroma volatiles dominated the samples fried at 150 degrees C, while those from Maillard reactions mostly prevailed in the aroma profile at 250 degrees C. PMID- 22063655 TI - Effect of cooking bag and netting packaging on the quality of pork ham during water cooking. AB - As a preliminary test for combining water cooking with vacuum cooling in soup of pork ham, three package treatments were designed to study the effect of cooking bag and netting on the quality of water cooked ham, i.e. ham cooked with a cooking bag and without a cooking bag (single netting and double netting). For treatments without a cooking bag, the results indicated that there was no significant superiority of ham cooked with double netting compared with ham cooked with single netting on the processing efficiency and quality characteristics. Although the hams cooked with a bag performed better in some chemical retentions and pigment, the water contents were significantly lower than those hams cooked in single netting (P<0.05), and there was a higher shrinkage tendency compared with the hams cooked without a bag. For the processing characteristics and texture properties of pork ham, there were no significant differences observed among the treatments with and without a cooking bag in terms of the combined effect of cooking and cooling (P>0.05). By considering the safety, convenience, cost, and the recovery effect on the quality changes of ham during vacuum cooling in soup, cooking with single netting is a better choice for future research. PMID- 22063656 TI - Temporal changes in glycogenolytic enzyme mRNAs during myogenesis of primary porcine satellite cells. AB - The objective was to study the regulation of glycogenolytic enzyme mRNAs in porcine satellite cells during proliferation and differentiation. Beyond 80% confluence, cells were grown in absence or presence of 1MUM insulin. The observed increases in abundance of mRNA for glycogenin, glycogen synthase, phosphorylase kinase, phosphorylase and glycogen debranching enzyme, and no alterations of the transporter molecule GLUT4, clearly indicate that glycogenolytic enzymes of potential importance to meat quality development are regulated at the gene level during myogenesis, and are heavily involved in muscle cell and muscle fibre development. The genes, however, are not influenced by insulin, and the lack of response to insulin of expression of gene-encoding enzymes involved in the formation and degradation of glycogen may question the applicability of porcine cell culture systems, like the one applied, as a model to study the regulation and regulatory mechanism of energy metabolism in muscles. PMID- 22063657 TI - Effect of rosemary extract, chitosan and alpha-tocopherol on lipid oxidation and colour stability during frozen storage of beef burgers. AB - The effect of rosemary extract, chitosan and alpha-tocopherol, added individually or in combination, on lipid oxidation and colour stability of frozen (-18 degrees C) beef burgers stored for 180 days was investigated. The burgers' lipid oxidation and appearance were evaluated through measurement of primary (conjugated dienes and peroxide value) and secondary (malondialdehyde) oxidation products, together with visual assessment and instrumental measurement of colour. Chitosan alone and in combination with either rosemary or alpha-tocopherol had the best antioxidative effect (P?0.05) compared to individual use of rosemary or alpha-tocopherol, while the best results were obtained with the combination of chitosan and rosemary. The differences of antioxidative effects, however, between individual use of rosemary or alpha-tocopherol as compared to the controls were also significant (P?0.05). Chitosan added individually or in combination with either rosemary or alpha-tocopherol had also a noteworthy effect on the burgers' appearance as it contributed to red colour retention for a much longer period (P?0.05) compared all other treatments and the controls. In conclusion, the best antioxidative effects were obtained with the combination of chitosan and rosemary extract. PMID- 22063658 TI - Effects of a humidity-stabilizing sheet on the color and K value of beef stored at cold temperatures. AB - The effects of a humidity-stabilizing sheet containing glycerol, on the color and K value of beef stored at cold temperatures were investigated in this study. A drip-absorbing sheet seems to be effective for the preservation of meat quality, while a humidity-stabilizing sheet containing glycerol prevents the increase of metmyoglobin in cold stored beef. Maintaining samples wrapped in humidity stabilizing sheets containing glycerol at low temperature for 7days was a functional method for conserving the concentration of inosine monophosphate. Beef samples wrapped in sheets containing glycerol had lower K values than samples wrapped in sheets not containing glycerol. When the surface of the meat starts to desiccate, the humidity-stabilizing sheet releases moisture that has been absorbed from the beef in the early stages of storage. Thus, glycerol could potentially play a role as a humidity-stabilizing controller and color preservative. This research suggests that a humidity-stabilizing sheet containing glycerol is a useful moisture controller and prevents deterioration of meat quality, discoloration, and desiccation. PMID- 22063659 TI - The effects of shelf-life enhancers on E. coli K12 survival in needle-injected, surface contaminated beef strip steaks enhanced using recycled solutions. AB - The objective of this study was to evaluate the efficacy of shelf-life enhancers (sodium lactate [SL] or sodium lactate+sodium diacetate [SLDA]) on limiting the growth of Escherichia coli K12 in needle-injecting surface-contaminated beef strip steaks with recycled enhancement solutions. Strip loins were injected to 10% over initial weight. SLDA was most effective in controlling bacterial growth followed by SL alone. The salt/phosphate combination in the enhancement solution was ineffective. SL decreased a(*) (less red) and b(*) values (less yellow) of the steaks compared to the salt/phosphate control. SLDA decreased L(*) values compared to SL alone. SL and SLDA were equally effective in reducing purge loss from the steaks. Steaks enhanced with a "fresh" enhancement solution had higher a(*) values (more red) and higher E. coli contamination levels than steaks enhanced with recycled solutions. Recycling did not affect L(*) value, b(*) value, or purge loss. PMID- 22063660 TI - Textural and sensory properties of low fat pork sausages with added hydrated oatmeal and tofu as texture-modifying agents. AB - Low fat sausages were prepared with added hydrated oatmeal or tofu as texture modifying agents at levels of 10%, 15%, and 25% (w/w), respectively. The effects of the type and level of texture-modifying agents on the physical and sensory properties of low fat sausages were investigated. The water-holding capacity in sausage products increased by increasing the hydrated oatmeal level, but no significant differences was observed by the addition of tofu. The higher level of the agents produced a sausage product with less cooking loss and with a softer texture. The moisture absorption measurements suggest that the decrease in hardness of oatmeal-added sausage products may be due to the higher water retention properties of oatmeal in response to heat treatment, while that of tofu added sausage products may be associated with a weaker internal structure of tofu than the pork loin. The sensory evaluations indicated that the greatest overall acceptability in a low fat sausage was attained when the hydrated oatmeal or tofu were at their 15% addition level, respectively. PMID- 22063661 TI - Effect of different carbon dioxide concentrations and exposure times in stunning of slaughter pigs: Impact on animal welfare and meat quality. AB - The objective of this study was to determine the impact of different slaughter procedures on animal welfare and meat quality. Before slaughter in a dip-lift, one-gondola system, 460 pigs were exposed to an atmosphere containing either 80% or 90% CO(2) for 70 or 100s, and at the longer exposure time with stun-to-stick intervals of either 25-35 or 40-50s. Clinical parameters (reflexes, catecholamines and lactate) showed deficiencies in animal welfare after stunning with 80% CO(2) for 70 and 100s, with an interval of 40-50s, and with 90% CO(2) for 70s. Stunning with 80% CO(2) for 70 or 100s always induced stress, as indicated by higher lactate levels, and reduced meat quality as indicated by low pH(24) values (5.4 in Musculus longissimus and 5.5 in Musculus semimembranosus) and low impedance (Py(24)) values, especially in combination with the longer stun to-stick interval (40-50s). Stunning with 80% or 90% CO(2) in a dip-lift system was found to be acceptable for animal welfare (percentage of clinical reflexes) only in combination with the longer exposure time of 100s and the shorter stun-to stick times of 25-35s. When 90% CO(2) was used, the longer stun-to-stick interval of 40-50s also gave results acceptable with regard to animal welfare. Generally, in comparison to 80% CO(2) stunning meat quality was superior (higher pH(24) and Py(24) values) after stunning with 90% CO(2). PMID- 22063662 TI - Antioxidant status and odour profile in fresh beef from pasture or grain-fed cattle. AB - The main goal of the present work was to determine the overall antioxidant status in fresh meat from animals fed different diets and to differentiate them through their odour profiles. Attributes were evaluated in beef from pasture or grain-fed animals with (PE and GE) or without supplementation (P and G) with vitamin E (500UI/head/day). Fresh meat produced on pasture (P and PE) had higher total ferric reducing antioxidant power (FRAP) levels than meat from grain fed-animals (G and GE) (P<0.05). However, no differences were found on their ability to reduce ABTS(+) (2,2'-azino-bis-(3-ethylbenz-thiazoline-6-sulfonic acid)), indicating that total antioxidant activity was preferentially due to the reduction potential than to the quenching capacity of tissue homogenates. Two fold glutathione (GSH and GSSG are the reduced and oxidised forms, respectively) levels were found in the P+PE group respect to G+GE meat (P<0.001). In addition, meat from pasture-fed animals presented a higher glutathione redox potential compared to grain-fed animals (-156.1+/-6.1 and -158.1+/-6.5 vs. -148.1+/-13 and 149.8+/-14.6 for P, PE G and GE, respectively), showing that the antioxidant status in fresh meat was affected by diet. Enzymatic activity of catalase and glutathione peroxidase were equivalent for all dietary groups. Only superoxide dismutase activity was slightly higher (P<0.05) in the P+PE group than in G+GE samples. Odour profile analysis was performed in relationship to antioxidant parameters. Significant linear correlation coefficients (P<0.05) were found for a set of sensors and the FRAP values. E-nose methodology successfully discriminated the odour characteristics of samples corresponding to pasture- or grain-based diet. Hence, it was possible to describe an analytical relationship between the odour profile and the antioxidant power of fresh meat. PMID- 22063663 TI - Chemical equilibrium of minced turkey meat in organic acid solutions. AB - The distribution of acid (HA), anions (A(-)), free protons (H(3)O(+)) and bound protons (H(b)), in homogenized turkey meat was evaluated at various meat/water mass ratios of (1/4-1/10) during titration with acetic acid (0.25N) or lactic acid (0.2N). H(b) concentration was determined by titration with hydrochloric acid (0.075N) and a correlation for [H(b)]=f(pH) was proposed. A procedure was used to calculate the fractions of the various species in equilibrium, starting from an initial acid concentration in a meat/water system and assuming the accuracy of the pK(a) value of the pure weak acids despite the chemical complexity of meat. Calculated results were in very good agreement (+/-0.15) with experimental pH values, whatever the acid, meat batch or meat/water mass ratios used. Less than 1% of the total protons were free (H(3)O(+)) and determined the meat pH. PMID- 22063664 TI - Lipolytic and oxidative changes in Iberian dry-cured loin. AB - This study was conducted using 61 Iberian pigs from four different genetic lines fattened under two different rearing systems. Fatty acid composition of neutral lipids (NL), polar lipids (PL) and free fatty acids (FFA) of the 61 fresh loins and their corresponding dry-cured loins and indices of lipid oxidation (hexanal, TBARS and rancid flavour) of the dry-cured loins were analyzed. Although the total amount of fatty acids from PL decreased most (89.77%), the fatty acid profile of FFA from dry-cured loin was more similar to that of NL from fresh loins. Monounsaturated fatty acids (MUFA) were the most abundant FFA type (260mg/100g muscle dry matter) followed by saturated fatty acid (SFA) (256mg/100g muscle dry matter) and polyunsaturated fatty acids (PUFA) (148mg/100g muscle dry matter). Neither genetic line nor rearing system showed any significant (P>0.05) effect on the decrease of fatty acids in the lipid fractions studied. The important decrease in PUFA from NL (43.70%) and PL (89%) was not reflected in higher oxidative indices in dry-cured loin. Neither PCA nor Pearson's correlation showed any clear relationships between lipolytic changes and oxidative indices. PMID- 22063665 TI - Carcass, sensory, fat color, and consumer acceptance characteristics of Angus cross steers finished on ryegrass (Lolium multiflorum) forage or on a high concentrate diet. AB - Fall-born Angus-cross steers (n=30) from 1 of 2 sires, were randomly assigned to either an 85% corn, 7.5% cotton-seed hulls, and 7.5% vitamin/mineral/urea supplement diet (GRAIN), 100% ryegrass grazing (RG), or ryegrass grazing then the GRAIN diet for 94d (RG/GRAIN). USDA Yield Grade of steers finished on either the GRAIN or RG/GRAIN regimens were higher (P<0.02) compared to those finished on RG. Marbling score and USDA Quality Grade did not differ (P=0.21 and 0.12, respectively) among the three finishing regimens. Yellowness (b(*)) values of the subcutaneous fat from both strip loins (SL) and ribeye (RE) rolls was lowest (P<0.05) in cuts taken from steers finished on GRAIN. Subcutaneous fat of both SL and RE had lower L(*) and hue angle values, and higher a(*) and b(*) values before trimming than after the fat was trimmed to 0.3cm. Initial and sustained tenderness scores of SL from steers finished on GRAIN were higher when compared to RG/GRAIN or RG regimens (P<0.05). Flavor intensity and beef flavor scores were higher (P<0.05) for SL from GRAIN- or RG/GRAIN-finished steers compared to RG finished steers. GRAIN SL had lower (P<0.05) WBSF values than RG, but similar (P>0.05) to RG/GRAIN. Trained sensory tenderness and flavor scores and WBSF values for RE were not affected by finishing regimen (P>0.05). GRAIN steaks had a higher consumer overall acceptability score, average price/kg, and rank (P<0.05). While carcass, fat, and sensory disadvantages were present in RG cattle, the overall magnitude of the differences compared to GRAIN cattle was fairly small. PMID- 22063666 TI - Effect of electrical stimulation on quality of tenderstretched chevon sides. AB - Thirty male Black Bengal goats 5-8 years of age, slaughtered at the Kolkata slaughter house, India, by the traditional 'halal' method, were used to assess the effect of electrical stimulation on tenderstretched sides of chevon carcasses. Five groups (T1, T2, T3, T4 and T5) were treated with variable voltages of 35, 110, 330, 550, 1100 with fixed 50Hz and 10pulses/s for a duration of 3min. Different quality parameters, such as, fibre diameter, sarcomere length, water holding capacity (WHC), pH, microbial content and taste panel score were studied at 24 and 48h post-stimulation. pH, WHC and fibre diameter decreased whereas sarcomere length showed an increasing trend in electrically stimulated meat, which was also microbiologically more stable. The non-stimulated control meat was tougher than the electrically stimulated chevon as evident through taste panel scoring. Treatment 3 (T3), i.e. 330V, 50Hz and 10pulses/s, showed superiority over the other four treatments in the majority of the important meat quality parameters. PMID- 22063667 TI - Evaluation of the oxidation state and metal concentration in the adipose tissue of Parma ham. AB - The effect of different dietary fat supplements: A, no added fat; B, 3% added lard and C, 3% added partially hydrogenated lard (PHL), were evaluated in dry cured Parma ham fat by determination of the lipid oxidation indices, R1 and R2, on a total of 30 Italian Landrace*Italian Large White pigs. Furthermore, correlations between lipid oxidation and calcium, magnesium, iron, zinc, copper and nickel concentrations, determined in Parma ham fat, was also investigated. Results highlighted a correlation between the oxidative state of Parma ham fat and the pigs' diet; in particular the addition of 3% PHL led to a more stable depot fat towards lipid oxidation compared to the addition of lard. Finally, Parma ham fat from treatment C showed higher concentrations of Ca (p<0.01) and Mg (p<0.05) compared to those from control, A, and treatment B groups. On the contrary, no significant differences were found for Fe, Zn, Cu and Ni. PMID- 22063668 TI - Muscle pH and temperature changes in hot- and cold-deboned ostrich (Struthio camelus var. domesticus) Muscularis gastrocnemius, pars interna and Muscularis iliofibularis during the first 23h post-mortem. AB - Cold-shortening is the response when muscles are exposed to temperatures below 10 degrees C with a pH>6.20. The course of pH within hot-deboned and intact ostrich M. gastrocnemius, pars interna and M. iliofibularis were followed for the first 23-24h post-mortem to investigate the changes in pH as well as to determine the point of minimum pH for ostrich muscles post-mortem. The hot-deboned muscles took longer to reach the point of minimum pH than the intact muscles. There was no significant (P=0.4508) difference in the minimum pH (5.91+/-0.26) between the hot deboned and the intact muscles. It was concluded that both the M. gastrocnemius, pars interna and the M. iliofibularis reached a pH<6.20 early post-mortem with muscle temperatures above 10 degrees C; and therefore showed no risk of cold shortening if these muscles were to be hot-deboned 2-4h post-mortem. PMID- 22063669 TI - Preliminary investigation of the effects of low-level dietary inclusion of fragrant essential oils and oleoresins on pig performance and pork quality. AB - Since the tissue characteristics of monogastric species are readily influenced by the composition of the feeds they consume, the objectives of this preliminary study were to assess the performance of finisher pigs on diets containing 0.05% of essential oils or oleoresins of rosemary, garlic, oregano, or ginger, and to determine the effect of these diets on pork quality. The pigs preferred the garlic-treated diet, and feed intake and average daily gain were significantly increased although no difference in feed efficiency was observed. Carcass and meat quality attributes were unchanged by dietary treatment, although a tendency towards reduction of lipid oxidation was noted in oregano-fed pork. Sensory panelists were unable to detect a flavour/aroma difference between treated and control pork. These results indicate that a higher level of dietary supplementation may be required in order to effect observable differences in pork characteristics. PMID- 22063670 TI - Meat fatty acid composition of llama (Lama glama) reared in the Andean highlands. AB - This study reports the results of the chemical analysis of the Longissimus thoracis and lumborum taken from 20 llama males, reared in the Andean highlands. The animals were slaughtered at 25 months and had a mean final body weight of 63kg. Llama meat shows a low fat (3.51%) and cholesterol content (56.29mg/100g). The fatty acid composition in llama meat contains 50.34% saturated fatty acids, 42.48% monounsaturated fatty acids and 7.18% polyunsaturated fatty acids. Llama meat appears to be a healthy alternative red meat choice. PMID- 22063671 TI - Contact dermatitis to the combination gel of adapalene 0.1% and benzoyl peroxide (PBO) 2.5%. PMID- 22063672 TI - Analysis of commercial proanthocyanidins. Part 1: the chemical composition of quebracho (Schinopsis lorentzii and Schinopsis balansae) heartwood extract. AB - Quebracho (Schinopsis lorentzii and Schinopsis balansae) extract is an important source of natural polymers for leather tanning and adhesive manufacturing. We combined established phyto- and synthetic chemistry perspectives with electrospray mass spectrometry experiments to prove that quebracho proanthocyanidin polymers consist of an homologous series of flavan-3-ol based oligomers. The starter unit is always catechin which is angularly bonded to fisetinidol extender units. By comparison of the MS(2) fragmentation spectra of the oligomer with product ion scans of authentic catechin and robinetinidol samples, we proved that quebracho extract contains no robinetinidol, as is often reported. Quebracho proanthocyanidins have acid resistant interflavanyl bonds, due to the absence of 5-OH groups in fisetinidol, and the aDP cannot be determined via conventional thiolysis and phloroglucinolysis. We used the MS data to estimate a conservative (minimum value) aDP of 3.1. PMID- 22063673 TI - Mould starter cultures for dry sausages-selection, application and effects. AB - The use of moulds on sausage surfaces can lead to both desirable and undesirable effects. The pursued effects are mainly related to successful production or consumer appeal. The undesirable effects are usually connected to growth of undesirable moulds. Most importantly, moulds may produce highly toxic secondary metabolites and beta-lactams. Inoculations of sausages with moulds were traditionally done with the indigenous flora of the processing plants, the so called houseflora, which was mainly composed of penicillia and aspergilli. The gradual shift in sausage production from small local producers to large-scale factories and increasing awareness of the risks for consumer safety has paved the way for industrialised procution of mould starter cultures. The industrialized starter cultures are carefully selected among hundreds of candidates going through multi-stage concepts including several analytical and biochemical investigations. While the technological aspects of mould inoculations are fairly resolved, its influence on prodution of secondary metabolites is yet emerging. Moulds produce enzymes for the degredation of lipid- and protein-matter, but studies show that the proteolytic and lipolytic capabilities differs significantly both between strains and is highly dependent on media, pH and temperature. Only few studies have addressed the aroma impact of mould growth on sausages, but information from related areas like milk based systems or sausage models still gives a quite clear picture of which components are important and their possible routes of information. One example is that methyl ketones play significant roles in the flavour of Blue cheeses. Here the presence and production of methyl ketones is ascribed to the beta-oxidation activities of moulds and therefore investigations in sausages flavour have successfully focused on confirming this relationship and its aroma influence. Sausage producers are interested in using the established knowledge on aroma formation in sausages for improving aroma and texture but also for shortening ripening periods or even expanding shelf life. Addition of concentrates of enzymes have yielded some positive results but it is clear that the use of enzymes as additives in sausages production is not straightforward. To ensure optimal consumer safety starter cultures should be applied to achieve maximal controll over the mould population. Starter strains should under no circumstances show pathogenic or toxigenic signs in neither chemical or biological test. Additionally they should not be able to produce antibiotics. PMID- 22063674 TI - Assessment of palatability attributes of the major beef muscles. AB - One kilogram roasts from 33 muscles or muscle groups from 25 Canada AA steer carcasses were evaluated for palatability after roasting to 72 degrees C internal temperature in an electric convection oven preheated to 177 degrees C. Initial tenderness ranged from moderately tough to tender. All butt tender and tenderloin samples were tender on the first bite, but less than 10% of the rib cap (top and lower portions), deckle point, brisket, and eye of round samples were rated tender on the first bite. Overall tenderness also ranged from moderately tough to tender. All of the tenderloin, butt tender, rib-eye cap, and cross rib samples were rated tender overall, but none of the deckle point samples were rated tender overall. Perceptible connective tissue ranged from slight to moderately abundant. Juiciness ranged from slightly dry to moderately juicy. All of the tenderloin, cross rib cap, rib-eye cap, tri tip, flap meat, short rib, and skirt samples were rated juicy, but 40% or less of the shoulder, eye of round, and loss side samples were rated juicy. Beef flavor intensity ranged from slightly to moderately intense, and flavor desirability ranged from slightly undesirable to moderately desirable. All tenderloin, butt tender, striploin, rib eye, and cross rib cap samples were rated desirable in overall palatability, but 25% or less of the rib cap (top and lower portions), shank meat, eye of round, brisket, and deckle point samples were rated desirable in overall palatability. To the extent desirability to the panel utilized is representative of consumer acceptance, only the tenderloin, butt tender, rib-eye cap, cross rib, cross rib cap, and rib-eye either met or came close to meeting the Canadian Cattlemen's Association's goal of 95% acceptance based upon palatability. Consequently, effective postmortem intervention techniques or alternative cooking methods must be developed and applied to improve the palatability of most beef muscles, if the aforementioned goal is to be achieved. PMID- 22063675 TI - Radio frequency cooking of ground, comminuted and muscle meat products. AB - The effect of radio frequency (RF) cooking, on the quality (colour, water holding capacity, texture), heating rate, and temperature history of three types of meat products (ground, comminuted and muscle), was investigated after heating to centre temperature of 72 degrees C in a 1.5 kW RF heater operating at 27.12 MHz. The results were compared with that obtained from heating in a water bath. RF cooking of processed meat products resulted in a decreased cooking time (5.83, 13.5, and 13.25 min for ground beef, comminuted meat, and muscle, respectively compared to 151, 130, and 109 min in water bath), lower juice losses, acceptable colour, water holding capacity and texture. The results indicate that when using RF, ground beef has the highest power efficiency (60.17%) followed by comminuted meat (44.41%), and muscle (43.38%). However, the texture of ground beef was too chewy and elastic. The muscle's colour was inferior. The comminuted and muscle meat products exhibited average energy efficiency with improved texture. The comminuted meat displayed a large cross-sectional temperature differential, possible due to uneven salt distribution. The well mixed comminuted and ground meat products appeared to be most promising for RF cooking. PMID- 22063676 TI - Staged injection marination with calcium lactate, phosphate and salt may improve beef water-binding ability and palatability traits. AB - Semitendinosus and longissimus muscles from USDA Select carcasses were used to investigate the effects of staged injection of calcium lactate followed by phosphate and salt (PS) on water-binding ability and palatability traits. Calcium lactate (0.2 M) and PS (8.4% and 4.2%, respectively) were sequentially injected (5.5% by weight) into muscles with 0, 1, 3, or 5 h holding time between injections. Treatments also included a double pump of 0.1 M calcium lactate with 0 h holding time between injections and a non-marinated control. Injection of calcium lactate and PS increased (P<0.05) pumped yield and decreased (P<0.05) expressible moisture values compared to calcium lactate injection only. No differences in peak force, total energy, or myofibrillar fragmentation index were observed among marination treatments for either muscle; however, longissimus tenderness was unusually high. Trained-panel evaluation of sensory traits did not differ for the semitendinosus muscle. Staged injection of calcium lactate and PS improved (P<0.05) myofibrillar and overall sensory tenderness scores of longissimus muscle over those of the non-marinated control. However, beef flavor intensity scores were lowered (P<0.05) by addition of PS. Holding time between injections did not appear to consistently influence water-binding ability or palatability traits. These data suggest that separate solutions of calcium lactate and PS may be injected into longissimus muscle to improve water-binding ability and palatability traits. PMID- 22063677 TI - Effect of grind size and fat levels on the physico-chemical and sensory characteristics of low-fat ground buffalo meat patties. AB - Two experiments were carried out to investigate the influence of grind size (3, 4 or 6 mm) and fat levels (6, 8, 10 or 20%) on the physico-chemical and sensory characteristics of low-fat ground buffalo meat patties prepared using a combination of carrageenan (0.5%) and sodium alginate (0.1%). At a constant fat level of nearly 8%, there was no significant difference (P>0.05) in the cooking yield, pH, proximate composition and dimensional changes of patties prepared at different grind sizes. However, shear force value increased significantly (P<0.05) with an increase in grind size. The sensory scores were significantly (P<0.05) higher for patties prepared using 3 mm grind size as compared to those prepared at 4 and 6 mm grind sizes and hence it was adopted as the optimum grind size for low-fat ground buffalo meat patties. At a constant grind size of 3mm, cooking yield, moisture, protein and gain in height were significantly (P<0.05) higher and shear force values were significantly (P<0.05) lower for patties at all low-fat levels as compared to the control with 20% fat. Based on its significantly higher (P<0.05) sensory scores, 10% fat level was selected as optimum for low-fat ground buffalo meat patties, although even at 8% fat level sensory rating remained between good to very good. PMID- 22063678 TI - The impact of single antimicrobial intervention treatment with cetylpyridinium chloride, trisodium phosphate, chlorine dioxide or lactic acid on ground beef lipid, instrumental color and sensory characteristics. AB - The effects of antimicrobial agents on ground beef were evaluated to determine if instrumental color, sensory or odor characteristics were impacted. Trimmings were treated with 0.5% cetylpyridinium chloride (CPC), 200-ppm chlorine dioxide (CLO), 0.5% lactic acid (LA), 10% trisodium phosphate (TSP), or an untreated control (C). Ground beef made from trimmings with CLO and TSP were similar (P > 0.05) in L(*) values to the control; however, samples were redder (a(*); P<0.05) than the control. Likewise, sensory panelists found ground beef from the CPC and TSP treatments redder (P<0.05) for worst point color than the control by day 2 of display. The CLO, CPC and TSP treatments were similar (P>0.05) to the control in beef odor intensity until day 3 of display. Therefore, the use of antimicrobial agents on beef trimmings may not adversely affect, and may improve bulk ground beef color and odor characteristics. PMID- 22063679 TI - Assessment of the chemical and cooking properties of the major beef muscles and muscle groups. AB - Thirty-three muscles or muscle groups were separated from 25 Canada AA beef carcasses. Each of these muscles and muscle groups was subsampled, and the contents of moisture, fat, soluble hydroxyproline, insoluble hydroxyproline, and total hydroxyproline were determined. In addition, a 1-kg roast from each muscle or muscle group was used to determine thaw-drip losses, cooking times, and total cooking losses. Cooking times ranged from 51.0 to 111.3 min/kg (S.E.=2.90). Thaw drip losses ranged from 1.26 to 10.05% (S.E.=0.40). Total cooking losses ranged from 21.51 to 33.26% (S.E.=0.70). Moisture content ranged from 666.4 to 761.8 mg/g (S.E.=0.23). Fat content ranged from less than 30 to 118.7 mg/g (S.E.=0.25). The amount of total hydroxyproline on a dry, defatted basis ranged from 17.8 to 117.4 MUMol/g (S.E.=2.24). Insoluble hydroxyproline ranged from 15.2 to 101.9 MUMol/g, (S.E.=1.70), and soluble hydroxyproline ranged from 2.1 to 30.9 MUMol/g (S.E.=0.78). Percent soluble hydroxyproline ranged from less than 10 to more than 30% (S.E.=0.79). Such wide variation in cooking and chemical properties undoubtedly has a considerable impact on the palatability attributes and consumer acceptance of beef. However, greater understanding of the chemical composition of muscle will provide a basis for the development of technologies to enhance the palatability of individual muscles and muscles groups. PMID- 22063680 TI - Effects of cooking beef muscles from frozen or thawed states on cooking traits and palatability. AB - Biceps femoris and longissimus lumborum steaks were cooked from either a frozen or thawed state on an electric belt grill (TBG-60 MagiKitch'n Inc., Quakertown, PA) at 93 degrees C to the endpoint temperature of 70 degrees C. Cooking loss, cooking time, Warner-Bratzler shear force (WBSF), and color (Illuminant A, L(*), a(*), b(*)) were evaluated. Trained panelists (n=6) evaluated palatability attributes on an eight-point scale for myofibrillar tenderness, juiciness, flavor, overall tenderness, and connective tissue amount (1=extremely tough, dry, bland, tough, and abundant; 8=extremely tender, juicy, intense, tender, and none). L(*), a(*), WBSF, juiciness, flavor, connective tissue amount, and overall tenderness did not differ (P>0.05) between steaks cooked from frozen and thawed states. However, thawed steaks cooked faster and had lower cooking losses than frozen steaks. The biceps femoris had higher WBSF values than the longissimus lumborum and was rated less tender by trained panelists. L(*), a(*), or b(*) values did not differ (P>0.05) between muscles. The biceps femoris needed more time to cook and had greater cooking losses than longissimus lumborum. Dimensional changes of steaks cooked to either 60 or 70 degrees C were studied. The width of biceps femoris steaks decreased 12.2%, and width of longissimus lumborum decreased 6.3%. Longissimus lumborum steaks became shorter (P<0.01) than biceps femoris steaks. Thickness of biceps femoris steaks decreased 25.6%, and thickness of longissimus lumborum steaks decreased 23.3%. Muscle type had a more pronounced effect on dimensional changes of steaks than endpoint temperature. PMID- 22063681 TI - Determination of animal skeletal maturity by image processing. AB - Color image features were computed to characterize the skeletal maturity of beef carcasses based on cartilage ossification in the thoracic vertebrae. A trained neural network was tested for predicting USDA beef maturity grades from image features of ossification. A feature curve was defined to characterize the color variations of an isolated cartilage-bone object. Both RGB and HSL color systems were used to derive image features. The maturity grades were assigned by an official USDA grader. Two sets of samples were obtained from two different meat processing plants. The first set contained samples of only A and B maturity grades whereas the second set had all five maturity classifications (A through E). The hue value was the most useful color feature. The mean hue values of cartilage differed (P<0.05) among the maturity grades and the feature curve based on the hue value was used as neural network input for maturity prediction. The accuracy of prediction was 75% for the first set of samples and 65.9% for the second set of samples. The results data show the potential of computer vision techniques for beef maturity assessment. PMID- 22063682 TI - Microbiological effects of carcass decontaminating treatments at four beef packing plants. AB - The effects on the microbiological conditions of carcasses of decontaminating treatments at four beef packing plants were examined. Spraying with 2% lactic acid, vacuum-hot water cleaning and trimming were generally ineffective. Washing reduced numbers of bacteria on carcasses when numbers were relatively high but not when they were relatively low. Pasteurizing with steam or hot water was consistently effective. The results suggest that the maximum reduction of bacteria on carcasses may be obtained by washing and pasteurizing without the other decontaminating treatments that are currently applied to carcasses. PMID- 22063683 TI - Assessment of the relationship between chemical components and palatability of major beef muscles and muscle groups. AB - The relationships of chemical components to palatability attributes in 33 different muscles and muscle groups from 25 Canada AA steer carcasses were assessed. Intramuscular fat and moisture accounted for 38.4 and 23.0% of the variation in panel juiciness ratings of all 33 muscles or muscle groups. Insoluble hydroxyproline content was more closely related with palatability attributes than either total or soluble hydroxyproline content, and accounted for 16.8, 26.0, 34.8, 24.0 and 34.8% of the variation in initial and overall tenderness, amount of perceived connective tissue, flavour desirability, and overall palatability, respectively, of all muscles. Exclusion of "sheet-like" support muscles improved the amount of variation accounted for in palatability traits slightly and exclusion of "combination cuts" containing two or more muscles improved the amount of variation accounted for in palatability traits significantly. Insoluble hydroxyproline not only adversely influenced textural properties contributing to tenderness, but also adversely influenced flavour desirability. The amount perceived connective tissue provides a reliable indication of the amount of insoluble hydroxyproline, and vice versa particularly in individual muscles, where the epimysium has been removed. PMID- 22063684 TI - The effects of multiple antimicrobial interventions on processing, lipid, textural, instrumental color and sensory characteristics when used in a ground beef patty production system. AB - The impact of multiple antimicrobial interventions on ground beef processing, lipid, textural, instrumental color and sensory characteristics were evaluated. Beef trimmings were treated with 0.5% cetylpyridinium chloride followed by 10% trisodium phosphate (CT), 200-ppm chlorine dioxide followed by 0.5% cetylpyridinium chloride (CLC), 200-ppm chlorine dioxide followed by 10% trisodium phosphate (CLT), or 2% lactic acid followed by 0.5% cetylpyridinium chloride (LC) and compared to an untreated control (C). Sensory panelists found LC and CT treatments similar (P>0.05) in grinding ability to C. By day 2 of display, CT, CLT and LC patties were redder (a(*); P<0.05) than C. Sensory panelists found CT patties redder (P<0.05) than C by day 2 of display. Sensory panelists found CT and CLT juicier than C. Therefore, the use of these multiple antimicrobial intervention agents on beef trimmings may improve sensory characteristics and shelf-life of ground beef patties. PMID- 22063685 TI - The effects of castration on the eating quality of dry-cured ham. AB - The influence of the castration of entire male pigs on the eating quality of dry cured ham was evaluated. Forty-eight dry-cured hams (435-day aged) were studied from entire and castrated males of two different crossbreeds. The proximate composition of the meat and the androstenone, indole and skatole fat content were determined. The entire hams were classified according to the androstenone and skatole content. Sensory analysis was carried out by a trained panel, evaluating marbling, juiciness, saltiness, graininess, toughness, overall flavour, boar odour and boar flavour. Also carried out was a preference and acceptability paired test by consumers. Castration increased meat fattening and reduced the androstenone and skatole levels of the fat. Significant differences (P<0.05) were found between entires and castrates for the average values given in all the sensory attributes studied. The dry-cured ham from castrates was scored as more flavoured, more marbled and softer. It was also perceived as less grainy, less salty and having less boar odour and flavour. The sensory perception of boar odour was more intense than that of flavour in dry-cured ham and appears to be related to the level of androstenone and skatole in fat. Dry-cured ham from castrated males was also more accepted and more preferred by consumers, especially women and habitual consumers. Castration of male pigs contributes to improve the quality of dry-cured ham. The rejection caused by boar odour and flavour is reduced, improving the overall flavour, texture and juiciness. In addition, the saltiness is less pronounced in ham from castrates. For this reason, the production of high quality dry-cured ham will have to shoulder the extra costs associated with processing castrated pigs. PMID- 22063686 TI - Effect of dietary linseed oil and alpha-tocopherol on pork tenderloin (Psoas major) muscle. AB - The effect of linseed oil and alpha-tocopheryl acetate on the fatty acid composition and the susceptibility to oxidation of lipid fraction from pork tenderloin (Psoas major) muscle has been studied. Muscles were obtained from animals fed on diets with the same ingredients excepting the oil source [sunflower (C), linseed (L) and linseed and olive (1/1, w/w) (LO)] and alpha tocopherol [20 (C, L and LO) or 200 (LOE and LE) mg/kg diet]. The n-6/n-3 ratio in pork tenderloin was markedly modified by dietary linseed oil administration, which was due to the increase in the C18:3n-3 (and total n-3 fatty acids) and the decrease in the C18:2n-6 (and total n-6 fatty acids) contents (P<0.05). The alpha tocopherol content of tenderloin from batches LE and LOE was about 2.8 mg/kg of muscle, significantly greater (P<0.05) than about 0.7 mg/kg muscle found in tenderloin from pigs receiving C, L and LO. Dietary supplementation with alpha tocopheryl acetate markedly reduced tenderloin lipid oxidation from animals fed diets enriched in n-3 fatty acids (L or LO vs LE or LOE). PMID- 22063687 TI - The influence of environment, mode of nutrition and animal species on level of nitrosamine contamination in venison. AB - The work aimed to research occurrence of nitrosamines in raw venison from different game species and mode of nutrition effect on their meat concentrations. Samples of venison from male and female elks, male and female red deer, male and female roe deer, male and female fallow deer, male and female wild boars, male and female brown hares and males and females of wild rabbits shot in Poland during the permissible hunting seasons were used for the experiments after their jointing and cutting. In the experiments conducted on eight species and 16 genera of wild male and female game animals a total of 336 analytical assays were conducted. Twenty-one meat samples of 1 kg each (each from a different animal) were collected respectively from males and females of eight animal species and taken to a laboratory. Meat contents of nitrosamines [dimethylonitrosamine (DMNA) and diethylonitrosamine (DENA)] were assessed by Pancholy's method adapted to nitrosamine determination in meat and meat products by Scanlan and Ryes. The levels of DMNA and DENA were determined using a Varian 3400 gas chromatograph coupled to a mass spectrometer (Finnigan MAT ITD. 800). Quantitative and qualitative analysis was conducted by comparison with N-nitrosamine standard solution chromatograms. PMID- 22063688 TI - Effects of chlorine dioxide, cetylpyridinium chloride, lactic acid and trisodium phosphate on physical, chemical and sensory properties of ground beef. AB - The impact of beef trimmings treated with either 0.5% cetylpyridinium chloride (CPC), 200-ppm chlorine dioxide (CLO), 2% lactic acid (LA) or 10% trisodium phosphate (TSP) and an untreated control (C) prior to grinding, on instrumental color, sensory characteristics, TBARS values, pH and Lee-Kramer shear under simulated retail display were evaluated. Trimmings were ground, pattied and sampled at 0, 1, 2, 3 and 7 days of display. Patties from LA, CPC and CLO treatments were lighter (L*; P<0.05) and TSP patties were redder (a*; P<0.05) than C. Panelists found TSP and CPC patties were similar or superior in beef and off odor to C on days 3 and 7 of display. Therefore, treatment of beef trimmings before grinding with TSP, CPC, CLO or LA may not only improve ground beef safety, but maintain or enhance patty shelf life. PMID- 22063689 TI - The relationship between pig genetics, myosin heavy chain I, biochemical traits and quality of M. longissimus thoracis. AB - The relationship between muscle biochemical traits, myosin heavy chain I and meat quality of longissimus thoracis was studied using gilts from five divergent porcine lines (A to E) (carcass weight: 83.7+/-8.7 kg). Intramuscular fat (IMF) and haem pigments content as well as myosin heavy chain 1 (MyHC I) percentage and the activity of lactate dehydrogenase (LDH) and isocitrate dehydrogenase (ICDH) were determined. Only group E, a well conformed line of pigs, included the halothane positive genotype. The presence of the Hal gene in this line resulted in meat of poorer quality in terms of meat of higher exudate compared to line D, also a well conformed line of predominantly Pietrain origin but being halothane gene free. Line C presented the highest IMF content (2.02%) as well as high oxidative characteristics (MyHC I, 10.0%; LDH/ICDH, 1.92 MUmol nmol(-1); ICDH activity, 1.78 nmol min(-1) g(-1)) and the lowest drip losses (5.3%). According to a principal component analysis including MyHC I, biochemical traits and meat quality parameters, line C was characterized by a high IMF content and oxidative traits, and line B by a high glycolytic metabolism. Line E was distinguished by high drip losses and by low pH(45) and pH(u). In conclusion, several observed differences in muscle metabolism between lines free of the halothane gene (A, B, C and D) must be caused by other "genetic background" factors. PMID- 22063690 TI - Factors influencing intention to purchase beef in the Irish market. AB - This paper reports on the findings of a study into consumer perceptions towards beef and the influence of these perceptions on consumption. Fishbein and Ajzen's [Belief, attitude, intention and behaviour. An introduction to theory and research (1995) Reading, MA: Addison-Wesley] Theory of Reasoned Action (TRA) provided a useful framework for this analysis. The influence of attitudes and important others (subjective norm) on intention to consume beef were explored. The findings support the usefulness of this model in understanding behaviour towards beef. In this study both attitude and the subjective norm influenced intention to consume beef, but it was attitude that was of greater importance. Health, eating enjoyment and safety were most important determinants of attitude with price, environment and animal welfare less so. An evaluation of the impact of the introduction of new information which related to one belief (health) was also conducted. Those indicating that they would consider increasing their consumption of beef had a more positive attitude towards beef and had more positive health and eating enjoyment beliefs about beef than the 'no' group who had significantly higher safety concerns. PMID- 22063691 TI - Physico-chemical characteristics of carcass and meat Manchego-breed suckling lambs slaughtered at different weights. AB - Forty-nine Manchego-breed lambs raised exclusively on their dams' milk until slaughter were used in this study. The effects of gender and slaughter weight (10, 12 and 14 kg) on carcass fatness, meat quality and the fatty acid composition of their fat were studied. Fatness, and in particular dorsal-fat thickness (P?0.01), increased with live weight. The effect of gender was even greater (P?0.001), as female lambs presented the highest fatness values for all parameters studied. The smallest drop in m. longissimus pH values was seen in the lowest-weight (10 kg) lambs. These same lambs displayed the highest L(*) value and thus the lightest colour. Fatty acid composition, which was not influenced by live weight, was affected by gender. The subcutaneous fat of female lambs contained more linolenic acid (C18:3) (P?0.01) and a greater proportion of polyunsaturated fatty acids than that of male lambs (P?0.001). Likewise, the intramuscular fat of female lambs displayed a greater proportion of monounsaturated fatty acids (P?0.001) than that of male lambs. PMID- 22063692 TI - Labelling information demanded by European consumers and relationships with purchasing motives, quality and safety of meat. AB - Meat labelling can be an important way of informing the consumer on the quality attributes of meat. However, the type of information consumers demand is not well known and there is a lack of consumer-oriented information. Thus, meat labelling requires special attention. The objectives of this paper were: to identify the type of information that is most demanded by European consumers on beef and lamb labelling; to analyse the relationships between the importance of informational cues and other aspects concerning consumer attitudes towards meat consumption and meat quality, and socio-demographic characteristics; and to identify groups of consumers according to their labelling preferences. The information cues considered most important related to the deadline for meat consumption and the origin of meat. Other important cues were nutritional information, maturation time, name of cut and, especially for beef consumers, information on the system of production and on the traceability and the quality control of the meat. Some groups or segments of consumers were identified that had significant differences in relation to the type of information demanded, purchasing motives, quality preferences, sources of information on quality they trusted most and socio economic features. They could be briefly profiled as: 'quality/safety orientated'; 'traditional'; 'quality unconcerned/ convenience-driven' and 'origin motivated' consumers. PMID- 22063693 TI - Prediction of color, texture, and sensory characteristics of beef steaks by visible and near infrared reflectance spectroscopy. A feasibility study. AB - Color, instrumental texture, and sensory attributes of steaks from 24 beef carcasses at 2, 4, 8, 14, and 21 days post mortem were predicted by visible/near infrared (visible/NIR) reflectance spectroscopy in 400-1080 nm region. Predicting the Hunter a, b, and E* yielded the coefficient of determination (R(2)) in calibration to be 0.78-0.90, and R(2) was between 0.49 and 0.55 for tenderness, Hunter L, sensory chewiness and juiciness. The prediction R(2) for tenderness was in the range of 0.22-0.72 when the samples were segregated according to the aging days. Based on partial least square (PLS) model predicted tenderness, beef samples were classified into tender and tough classes with a correct classification of 83%. Soft independent modeling of class analogy of principal component analysis (SIMCA/PCA) model of measured tenderness showed great promise in the classification of tender and tough meats with over 96% success. PMID- 22063694 TI - Rapid detection of chicken and turkey in heated meat products using the polymerase chain reaction followed by amplicon visualisation with vistra green. AB - A rapid and highly specific assay suitable for the routine detection of turkey and chicken in processed meat products has been developed. Based on PCR amplification of species-specific amplicons with rapid visualisation using vistra green, the assay may be completed within 5 h of receipt of sample. DNA was isolated from meat samples by the use of Wizard DNA isolation technology and followed by DNA amplification in the polymerase chain reaction using species specific primers, chicken forward (CF), chicken reverse (CR), turkey forward (TF) and turkey reverse (TR): the production of an amplicon was detected after the end of the PCR in less than 5 min using vistra green and a fluorescence plate reader. The presence of fluorescence denoted the presence of the target species in the sample. PMID- 22063695 TI - A comparison of warmed-over flavour in pork by sensory analysis, GC/MS and the electronic nose. AB - Pork muscle samples (M. longissimus dorsi and M. psoas major) were obtained from pigs given one of 4 dietary treatments, (i) control diet, (ii) supplemental iron (300 mg iron (II) sulphate/kg feed), (iii) supplemental vitamin E (200 mg dl alpha-tocopheryl acetate/kg of feed) and (iv) supplemental vitamin E+supplemental iron. Warmed-over flavour (WOF) was evaluated by a trained sensory panel (n=8) for the four treatments cooked and refrigerated at 4 degrees C for up to 5 days. Gas chromatography mass spectrometry (GC/MS) and Electronic nose analysis was performed on a subset of the full design which included samples of M. longissimus dorsi, treatments (ii) and (iii) and M. psoas major with treatment (i) for 0 days of WOF development. Day 5 of WOF development was included in the subset and represented by samples of M. longissimus dorsi, treatment (iv) and M. psoas major, treatments (ii) and (iii). Bi-linear modeling was used to determine the correlation of GC/MS and electronic nose data to sensory data. Also, the reproducibility and reliability of electronic nose data was evaluated by repeating the analysis of samples in a different laboratory and with a time difference of approximately 11 months. Mean-centring was used to normalise the data from these two different electronic noise data sets. GC/MS data correlated to sensory data with specific compounds (e.g., pentanal, 2-pentylfuran, octanal, nonanal, 1-octen-3-ol and hexanal), proving to be good indices of oxidation in cooked samples of M. longissimus dorsi and M. psoas major. Electronic nose data correlated to sensory data and separated the sensory variation. The reproducibility of this data was high with the second set of samples being predictive of the first set. PMID- 22063696 TI - Oxidative and colour changes in meat from three lines of free-range reared Iberian pigs slaughtered at 90 kg live weight and from industrial pig during refrigerated storage. AB - The oxidative stability and colour evolution during refrigerated storage (10 days at +4 degrees C) of Longissimus dorsi muscle from three lines of Iberian pigs and industrial genotype pigs were studied. The Iberian pigs were reared in an extensive system and fed on a commercial feed with access to pasture grazing, while industrial genotype pigs were reared in an intensive system. Fresh Longissimus dorsi of Iberian pig lines showed a more intense and redder colour, with a statistically significant higher CIE chroma and a*-value as well as a lower L*-value (P<0.05) compared with those of industrial genotype pigs. Pig genotype significantly affected the colour and lipid oxidation changes of m. Longissimus dorsi during refrigerated storage. The decrease in L*-value during the refrigerated storage was more intense in industrial pig's Longissimus dorsi than in those from Iberian pig lines. CIE a*-value decrease was more intense in 'Lampino' Iberian line and industrial Longissimus dorsi than in the other two Iberian pig lines, however CIE a*-value was significantly higher in muscles from Iberian pig lines than in muscle of industrial genotype (P<0.05) at the end of refrigerated storage. The Iberian and industrial pig's Longissimus dorsi did not show statistically significant differences in TBA-RS values (mg MDA/kg meat) at the end of the refrigerated storage period (P>0.05). To establish relationships between parameters measured in fresh meat and oxidation and colour changes during refrigerated storage, correlations and multiple regression models were calculated. CIE a*-values at day 10 were positively correlated with values of fresh muscles for a*, C18:1 percentages and negatively correlated with polyunsaturated fatty acids percentages of neutral and polar lipids. Inversely, TBA-RS values at day 10 showed a positive correlation with initial values for phospholipid content and polyunsaturated fatty acids of neutral and polar lipid fractions, while C18:1 percentage were negatively correlated. PMID- 22063697 TI - Commercial antioxidants control lipid oxidation in mechanically deboned turkey meat. AB - Effects of commercial rosemary antioxidants on oxidative stability of mechanically deboned turkey meat (MDTM) compared with Trolox C (vitamin E), ascorbic acid (vitamin C) and control without antioxidant were investigated. Antioxidants were added to meat at three levels. Thiobarbituric acid (TBA) assay and dynamic headspace gas chromatography were used to assess the effects of commercial antioxidants on lipid stability of MDTM during 7 months of frozen storage. Increased levels of TBA-reactive substances (TBARS) and volatile carbonyl compounds were noticed in all meat samples during storage, however most distinctly in meat without antioxidants. Retarding effect of antioxidants on the development of oxidation depended on the level and type antioxidants. Trolox C-a water soluble, synthetic derivative of vitamin E possessed the greatest antioxidative activity reflected by the lowest values of TBARS and volatile compounds. Ascorbic acid was less efficient than Trolox C and Biolox HT-W (rosemary), but more potent than most rosemary extracts in suppressing lipid oxidation especially in the long term frozen storage MDTM. The DPPH() method confirmed that antioxidant activity depends on the concentration of active compounds present in the samples available to scavenge the free radicals formed during the storage period. Supplementation of MDTM with antioxidants could be an alternative method to prevent oxidative degradation of the meat during frozen storage when vacuum packaging is not practical. PMID- 22063698 TI - Oxidative and lipolytic deterioration of different muscles from free-range reared Iberian pigs under refrigerated storage. AB - Three different type of muscles, two glicolytic (Serratus ventralis and Longissimus dorsi) and one oxidative (Masseter) were displayed under refrigeration at +4 degrees C during 10 days to evaluate differences in lipolytic and oxidative changes of different muscles with different metabolic pattern. Thiobarbituric acid reactive substances (TBARS), phospholipid content, hexanal content and fatty acid profiles of neutral and polar lipid fractions were analysed at day 0 and day 10. Phospholipid content (g phospholipids/g intramuscular fat) significantly (P<0.035) decreased from day 0 to day 10 in m. Masseter (0.33 vs. 0.25, respectively), but not in m. L. dorsi (0.12 vs. 0.09, respectively) and m. S. ventralis (0.19 vs. 0.14, respectively). Changes in fatty acid profiles of neutral and polar lipids significantly differed among muscles after storage. Slight differences were found in neutral lipids from m. L. dorsi and m. S. ventralis, while neutral lipids from m. Masseter were highly altered. Great changes affected fatty acid profiles from polar lipids in the three muscles. m. Masseter muscle showed significantly higher (P<0.000) TBARS values (1.13, 0.65 and 0.60 mg MDA/kg meat, respectively) and hexanal content (689.2, 241.2 and 355.8 MUg/g meat, respectively) than m. L. dorsi and m. S. ventralis. In conclusion, oxidative meat is more prone to oxidative and lipolytic deterioration than glycolytic muscles during refrigerated storage and as a consequence of that a lower shelf-life. PMID- 22063699 TI - The effects of sodium lactate and starter cultures on pH, lactic acid bacteria, Listeria monocytogenes and Salmonella spp. levels in pure chicken dry fermented sausage. AB - Two starter cultures (A and B) and seven sodium lactate concentrations were evaluated for chicken raw dry-fermented sausage processing. Starter culture B contained more lactic acid bacteria and less staphylococci than starter A. Their effects on acidification and inhibition of pathogens (Listeria monocytogenes and Salmonella spp.) were monitored. Starter culture B grew faster and was less inhibited by sodium lactate, thus inducting a faster and more important pH drop into the sausages. With lower pH, sausages processed with B starter were less contaminated by Listeria monocytogenes. The type of starter was found to influence the end-product pH, lactic acid bacteria content and extent of Listeria monocytogenes contamination. A 30-member panel did not note differences between sausages processed with the different starter cultures when lactate was added. Adding sodium lactate to the sausage mix reduced the pH drop in the dry sausage product. This acidification inhibiting effect of sodium lactate was greater for A. Sodium lactate significantly inhibited lactic acid bacteria development but did not reduce Listeria monocytogenes contamination frequency of the batches, unlike in many literature data. Sodium lactate may however control the acidification of the sausage processed with starter B, in order to obtain moderately acidified fermented sausages. A simple kinetic model was applied to our data. The sodium lactate content and especially the type of starter culture often had a significant effect on the four parameters of this empirical model (lag time, acidification time, initial and final pH). PMID- 22063700 TI - Detection of Iberian ham aroma by a semiconductor multisensorial system. AB - A semiconductor multisensorial system, based on tin oxide, to control the quality of dry-cured Iberian hams is described. Two types of ham (submitted to different drying temperatures) were selected. Good responses were obtained from the 12 elements forming the multisensor for different operating temperatures. Discrimination between the two types of ham was successfully realised through principal component analysis (PCA). PMID- 22063701 TI - High pressure processing applied to cooked sausage manufacture: physical properties and sensory analysis. AB - Vacuum-packaged cooked sausages were treated at 500 MPa for 5 or 15 min at mild temperature (65 degrees C). Colour, texture and yield of pressure-treated sausages were evaluated, and compared to those of sausages treated with a conventional heat pasteurisation (80-85 degrees C for 40 min). Colour attributes did not change. Pressurised sausages were more cohesive and less firm than heat treated sausages. Pressure treatment induced higher yield than heat treatment. Sensory analysis was also carried out. In some cases, the sensory panel did not detect differences between both types of sausages; and when there were differences, pressurised samples were preferred in more occasions because of their better appearance, taste and, especially, texture. High pressure processing can replace the second industrial heat treatment of cooked sausages. PMID- 22063702 TI - The effects of dietary oregano essential oil and alpha-tocopheryl acetate on lipid oxidation in raw and cooked turkey during refrigerated storage. AB - The effects of dietary oregano essential oil and alpha-tocopheryl acetate supplementation on the susceptibility of raw and cooked turkey breast and thigh meat to lipid oxidation during refrigerated storage for 9 days were examined. Thirty 12-week-old turkeys were divided into five groups and fed a basal diet containing 30 mg alpha-tocopheryl acetate kg(-1) feed as control, or basal diet plus 200 mg alpha-tocopheryl acetate kg(-1), or basal diet plus 100 mg oregano oil kg(-1), or basal diet plus 200 mg oregano oil kg(-1), or basal diet plus 100 mg oregano oil and 100 mg alpha-tocopheryl acetate kg(-1), for 4 weeks prior to slaughter. Lipid oxidation was assessed by monitoring malondialdehyde formation in raw and cooked meat at 0, 3, 6 and 9 days of refrigerated storage, through use of a third-order derivative spectrophotometric method. Results showed that all dietary treatments significantly (P<0.05) increased the stability of both raw and cooked turkey meat to lipid oxidation compared with the control. Oregano oil at 200 mg kg(-1) was significantly (P<0.05) more effective in delaying lipid oxidation compared to the level of 100 mg kg(-1), equivalent to alpha-tocopheryl acetate at 200 mg kg(-1), but inferior (P<0.05) to oregano oil plus alpha tocopheryl acetate at 100 mg kg(-1) each, which in turn was superior (P<0.05) to all dietary treatments, indicating a synergistic effect. Thigh muscle was more susceptible to oxidation compared with breast muscle in all treatments, although it contained alpha-tocopherol at significantly (P<0.05) higher levels. PMID- 22063703 TI - HIV-related stigma among nursing students in Cameroon. PMID- 22063704 TI - Toward a critical response to HIV criminalization: remarks on advocacy and social justice. PMID- 22063705 TI - Determination of an appropriate heat treatment of animal waste using the ELISA technique: results of a validation study. AB - Effective sterilisation of animal waste is an important prerequisite for the use of animal meal as an ingredient of compound feed for non-ruminants. Specific conditions for the rendering process aimed at the inactivation of the causative agent of Bovine Spongiform Encephalopathy (BSE), and the prevention of other pathogens in feedingstuff, are defined by European law. A validation study encompassing 21 laboratories from 12 European countries was performed using a commercially available test kit based on an enzymelinked immuno sorbent assay (ELISA) which allows proof of the appropriate heat treatment of the processed animal waste. The evaluation of the results regarding the R-value reveals the robustness of the method, a sufficient sensitivity to detect a deviation of the processing conditions from the regulation and a low standard deviation of the data. Moreover the statistical evaluation of the results allows for the estimation of the coefficient of variation which is between 11 and 22% depending on the magnitude of the response of the test. PMID- 22063706 TI - Application of hurdle technology for the development of Caprine keema and its stability at ambient temperature. AB - The study was envisaged to develop and extend the shelf life of the highly perishable Indian traditional meat product, chevon (capine) keema, through the application of hurdle technology.The hurdles used were water activity (a(w)) and pH as variable hurdles as well as vacuum packaging, preservatives and heat treatment as constant hurdles. The water activity of the product was adjusted to 2 levels viz., 0.90 and 0.88 by the addition of humectants. The product with 0.90 was preferred for sensory quality. The pH of the keema was adjusted with lactic acid to 3 desired levels viz. 5.50, 5.65 and 5.80. The product with pH 5.8 was the most acceptable and with pH 5.50 was the least acceptable. Standardised keema with a(w) 0.90 and pH 5.80 was stored at ambient temperature (36.2+/-1.2 degrees C) and evaluated for physico-chemical, microbiological and sensory characteristics. A gradual increase in moisture, a(w), thiobarbituric acid reactive substances (TBARS) number and tyrosine value were observed throughout the storage period. There was a decrease in the growth rate of aerobic and anaerobic counts and complete inhibition of Staphylococcus aureus. Although sensory scores for hurdle treated keema declined upon storage, the product was well accepted up to the 3rd day and fairly accepted up to 5th day whereas the keema prepared by the traditional method was acceptable only on the first day. Hurdle technology significantly improved the shelf life of keema. PMID- 22063707 TI - Effect of dietary vitamin E supplementation on beef colour stability. AB - The effect of dietary vitamin E upon colour, waterholding capacity, bacterial growth and lipid oxidation of beef longissimus thoracis (LT) and psoas major (PM) muscle were examined during aerobic display of fresh muscle and after aging in vacuum for 26 days. Forty crossbred beef bulls received a whole crop corn silage, supplemented with concentrate. Twenty bulls were each supplemented with 2025 mg vit E per day (added to the concentrate) for 136 day prior to slaughter and compared with non-supplemented control animals (n=20). In fresh LT muscle drip loss did not differ between treatment groups, while in PM muscle drip loss was significantly higher for the supplemented group. The treatment did not affect bacterial growth in fresh and aged muscles. Lipid oxidation during 12 day storage of fresh muscle was significantly lower for the supplemented group, as indicated by the lower TBA-values. No effect of the vitamin E treatment was observed on a (*)-values of both fresh and aged LT muscle during display for 8 and 5 days, respectively. In PM muscle, supplemented beef had lower a (*)-values in fresh (at day 1) and aged (at days 1 and 2) muscle, due to a lower oxygenation. The reason for this lower oxygenation is unclear. After aging, colour stability was decreased and more variable than in fresh muscle. Similar results were obtained when the difference in reflection values at 630 and 580 nm (R630-580), instead of the a (*) value, was used as a parameter for colour stability. The absence of an effect of vit. E on the rate of discoloration, might possibly be explained from the observation that alpha-tocopherol levels in control muscle were relatively high (LT: 2.1 and PM: 3.2 MUg/g muscle), compared with data from literature. Analysis of the feed for vit. E suggests that this was due to a relatively high natural vit. E uptake from the feed, which was calculated to be approx. 330 mg vit. E per animal per day for the control group. PMID- 22063708 TI - Postmortem changes in muscle electrical properties of bovine M. longissimus dorsi and their relationship to meat quality attributes and pH fall. AB - Heifers (n=47) were slaughtered and hung conventionally in an industrial meat plant. Electrical impedance (Py) and conductivity (EC) were studied for their ability to indicate or predict selected meat quality attributes i.e. Warner Bratzler shear force (WBSF), sensory tenderness, texture, flavour and acceptability, water holding capacity (WHC) and colour. pH, electrical impedance (meat check) and electrical conductivity (pork quality meter) measurements were taken at hourly intervals up to 8 h and again at 1 and 2 days postmortem. Electrical measurements were taken again at 7 and 14 days postmortem. Freshly cut steaks (2.5 cm thick) were taken from the longissimus dorsi (LD) muscle at 2, 7 and 14 days postmortem, vacuum-packaged in plastic bags and stored at -20 degrees C for WBSF and sensory analysis. Freshly cut steaks were used for WHC and colour measurements. During the development of rigor and over the ageing period, electrical changes occur in muscle tissue. Electrical measurements were found to change significantly between 1 and 14 days postmortem and when measured over the ageing period (at 2, 7 and 14 days postmortem) were significantly correlated to WBSF, sensory tenderness and Hunter 'a' and 'b' values (r=+/-0.56-+/-0.68, p<0.001) and weakly to moderately correlated to other sensory attributes (r=+/ 0.31-0.58, p<0.001) measured at the same times postmortem; thus showing potential for these rapid physical measurements as indicators of meat quality if both electrical measurements and quality attributes are measured at the same times postmortem and correlations are calculated over the ageing period. However, electrical measurements taken at specific times at the early postmortem period (i.e. at 1 or 2 days) showed only a few weak relationships with meat quality attributes measured at later times postmortem (i.e. 7 or 14 days) demonstrating that early postmortem electrical measurements are not suitable for the prediction of ultimate meat quality. Py values taken between 7 h and 7 days postmortem were significantly correlated with all pH measurements with the exception of 1 day values. Two day Py measurements showed the highest correlations (r=0.45-0.62, p<0.01-0.001) with pH. EC was also found to be moderately correlated with pH although correlations were slightly lower than those obtained for Py. Highest correlations (r=0.47-0.59, p<0.01) were obtained for 7 h values. PMID- 22063709 TI - Genomic identification of the breed of an individual or its tissue. AB - To elaborate a methodological approach for the assignment of a breed to a carcass or other animal tissue, DNA microsatellites were utilized. Four Italian beef breeds were studied; examining these breeds is a challenge because they display similar morphological and productive characteristics. As comparison 54 Holstein Friesian subjects were used. To measure the genetic similarities between animals or between groups of animals we used our method (Ciampolini et al, 1995, Individual multilocus genotypes using microsatellite polymorphisms to permit the analysis of the genetic variability within and between italian beef cattle breeds. Journal of Animal science,73, 3259-3268.) based on the consideration of a multilocus genotype of each animal, which enabled us to establish breed genomic formulae. Although the results are only preliminary, they show that we can distinguish easily between Holstein-Friesian subjects and beef animals; moreover we can identify, with a high resolution potential, animals from breeds (the four Italian white) with very high genetic similarities. However all the Holstein Friesian subjects were identified. PMID- 22063710 TI - Growth and effect of staphylococci and lactic acid bacteria on unsaturated free fatty acids. AB - The growth and the effects of four species of staphylococci and six lactic acid bacteria (LAB) of the genus Carnobacterium, Lactobacillus and Pediococcus on unsaturated free fatty acids were studied. The strains were grown in complex medium supplemented either with oleic, linoleic or linolenic acids. Growth was followed and oxidation of the substrates measured by TBARS. The strains of Staphylococcus xylosus 873, 16, Staphylococcus warneri 863 and Staphylococcus saprophyticus grew well on all the substrates. Whereas, the growth of the two strains of Staphylococcus carnosus and Staphylococcus xylosus 831 was inhibited in the media with linolenic acid. The addition of manganese to this media allowed good growth of these strains. All the LAB did not grow well in the media with linoleic acid, but their growth was favoured by addition of manganese to the media. Under our conditions, only linoleic and linolenic acids were oxidised. All the strains had no prooxidant activity. All the staphylococci limited oxidation of linoleic acid and had a small effect on linolenic acid. LAB did not limit oxidation of linoleic acid. With manganese in the media: the oxidation of the sterile controls was delayed for 2 days and then increased; strains of S. carnosus and S. xylosus inhibited oxidation of linolenic acid; and Lactobacillus plantarum and Pediococcus pentosaceus limited oxidation of linoleic acid. The two Carnobacterium, whatever the conditions, had no antioxidant properties. PMID- 22063711 TI - Colour stability and lipid oxidation of fresh beef. Development of a response surface model for predicting the effects of temperature, storage time, and modified atmosphere composition. AB - Samples of fresh beef muscles (Longissimus dorsi) were packed under varying modified atmosphere conditions (20-80% oxygen) and stored at 2-8 degrees C for 10 days. At 2 day intervals meat samples were analysed for surface colour and extent of lipid oxidation (TBARS). Response surface models for predicting the effects of temperature, storage time and modified atmosphere composition on colour stability and lipid oxidation were developed. Temperature and time were found to be the most important factors for retaining meat colour and minimizing lipid oxidation. However, the oxygen content also had a significant effect on both quality parameters. A stable interval of maintaining a good meat colour was found between 55 and 80% O(2). Response surface modelling was found to be very promising for modelling of chemical quality changes in meat stored under different conditions, but the large biological differences between animals may complicate the development of generally valid models. PMID- 22063712 TI - Heterogeneous composition of histochemical fibre types in the different parts of M. longissimus thoracis from Mishima (Japanese native) steers. AB - In Mishima (Japanese native) steers, histochemical properties of m. longissimus thoracis were examined at 3 parts: on the level of 6th thoracic (LT I), 11th thoracic (LT II) and 5th lumbar vertebra (LT III). Myofibres were categorized into Type I, II A and II B. The same fibre type composition (I, 37%, II A, 17%, II B, 46%) was observed at LT I and LT III and another (I, 26%, II A, 15%, II B, 59%) at LT II. At each part apparent regional differences of fibre type composition could not be demonstrated except for Type I between medial and lateral subpart at LT I and Type II A between central and lateral at LT III because of its marked variation among the individual steers. Relative fibre diameter of Type I to Type II A in the combined data was large at LT I and LT III. Type II B fibres showed larger diameter than Type I only at LT III. From these results it was suggested that Mishima steers have maintained another histochemical property of the longissimus muscle differing from that of Japanese Black steers (Gotoh, Iwamoto, Ono, Nishimura, Matsuo, Nakanishi, Umetsu & Takahara, (1994). Comparative study on the regional composition of fiber types in M. Longissimus thoracis with different marbling scores for Japanese Black steers. Animal Science and Technology, 65, 454-463). PMID- 22063713 TI - The characteristics of muscle fiber types of longissimus thoracis muscle and their influences on the quantity and quality of meat from Japanese Black steers. AB - Forty-four Japanese Black fattening steers from four groups, produced in four districts and consisting of differing genetic backgrounds were slaughtered to examine the characteristic differences in muscle fiber types at the 6th thoracic vertebra of the M. longissimus thoracis (LT). The influence of percentage, diameter, and relative area of each muscle fiber type on the carcass characteristics and some quantity and quality traits of beef taken from LT, were also investigated. Significant differences in the characteristics of the muscle fiber types were observed among the four groups, except for muscle fiber diameter in the alphaR fiber, and the relative area of each alphaW fiber. For all steers, the average percentages and diameters of each muscle fiber type, betaR, alphaR and alphaW were 26.8, 18.5 and 54.7% and 51.4, 50.6 and 52.4 MUm, respectively. The relative area of each fiber type was similar to those of muscle fiber composition. alphaR Fiber content had significant negative correlations with marbling score (p<0.05), intramuscular fat content (p<0.05) and ultimate pH value (p<0.05). Significant correlations between the diameter of each fiber type, and the quantity or quality traits of the meat were not found, with the exception of red fiber types (betaR and alphaR) and meat color a(*) values (p<0.05) which were positively correlated. PMID- 22063714 TI - Multivariate data analysis of Cavourmas - a Greek cooked meat product. AB - Physico-chemical and sensory analyses were performed on 48 samples of Cavourmas, a Greek traditional cooked meat product, bought directly from 16 known producers. The following physico-chemical attributes were determined: moisture, crude protein, ether-extractable fat, ash, NaCl, NaNO(2), NaNO(3), pH, TBA value, lightness (L (*)), redness (a(*)), and yellowness (b(*)). Principal component analysis based on three main axes (PC1, PC2 and PC3) accounting for 56.4% of overall variation showed that high consumer acceptability of Cavourmas is related to accepted taste and odour and to the presence of meat in pieces with red colour and white fat. On the contrary, fatty appearance, excessive melted fat and high rancidity were not appealing to the consumer, as confirmed by instrumentally determined high TBA values, high fat content, high percentage moisture and lightness, and should be kept low in order to enhance product acceptability. PMID- 22063715 TI - The effect of paprika, garlic and salt on rancidity in dry sausages. AB - Eight batches of ground fat and eight batches of a mixture of meat and fat (70 and 30%, respectively), were prepared by adding salt, paprika and garlic, in the proportions used for making chorizo - a dry fermented sausage - stuffed into natural casings and then ripened. The evolution of rancidity in these products was evaluated by means of total free fatty acid content, peroxide value and TBARS during the ripening period. Spanish paprika and salt showed antioxidant and prooxidant properties, respectively. Paprika was even able to inhibit the prooxidant effect of salt. Also, four batches of chorizo were made to compare the antioxidant effect of the spices (garlic and paprika) with a mixture of nitrate, nitrite and ascorbic acid. In this respect, paprika and garlic were as effective as the mixture of additives in inhibiting lipid oxidation. PMID- 22063716 TI - Warmed-over flavour in porcine meat - a combined spectroscopic, sensory and chemometric study. AB - The effectiveness of applying rapid spectral techniques in the prediction of meat quality in relation to pre-slaughter stress and warmed-over flavour (WOF) was investigated. The effect of pre-slaughter stress on the development of WOF is a relatively new area of interest in WOF research. The present study investigated the relationship between pre-slaughter stress and WOF characteristics (after 0 to 5 days' storage) in porcine meat as evaluated by chemical, sensory and spectroscopic methods. Sensory evaluation, visual reflectance spectroscopy (VIS) and low-field (1)H NMR (LF-NMR) proved efficient in describing the different stress groups and the storage period, whereas fluorescence spectroscopy and the TBARS test were only able to follow WOF during storage. Near Infrared Reflectance (NIR) and Raman scatter showed a very weak relationship to pre-slaughter stress and levels of WOF during storage. Good correlations (up to r=0.93) of sensory terms were achieved with VIS and fluorescence spectroscopy and LF-NMR. PMID- 22063717 TI - Brain pattern of histone H3 phosphorylation after acute amphetamine administration: its relationship to brain c-fos induction is strongly dependent on the particular brain area. AB - Recent evidence strongly suggests a critical role of chromatin remodelling in the acute and chronic effects of addictive drugs. We reasoned that Immunohistochemical detection of certain histone modifications may be a more specific tool than induction of immediate early genes (i.e. c-fos) to detect brain areas and neurons that are critical for the action of addictive drugs. Thus, in the present work we studied in adult male rats the effects of a high dose of amphetamine on brain pattern of histone H3 phosphorylation in serine 10 (pH3S(10)) and c-fos expression. We firstly observed that amphetamine-induced an increase in the number of pH3S(10) positive neurons in a restricted number of brain areas, with maximum levels at 30 min after the drug administration that declined at 90 min in most areas. In a second experiment we studied colocalization of pH3S(10) immunoreactivity (pH3S(10)-IR) and c-fos expression. Amphetamine increased c-fos expression in medial prefrontal cortex (mPFC), dorsal striatum, nucleus accumbens (Acb), major Island of Calleja (ICjM), central amygdala (CeA), bed nucleus of stria terminalis lateral dorsal (BSTld) and paraventricular nucleus of the hypothalamus (PVN). Whereas no evidence for increase in pH3S(10) positive neurons was found in the mPFC and the PVN, in the striatum and the Acb basically all pH3S(10) positive neurons showed colocalization with c-fos. In ICjM, CeA and BSTld a notable degree of colocalization was found, but an important number of neurons expressing c-fos were negative for pH3S(10). The present results give support to the hypothesis that amphetamine-induced pH3S(10)-IR showed a more restricted pattern than brain c-fos induction, being this difference strongly dependent on the particular brain area studied. It is likely that those nuclei and neurons showing pH3S(10)-IR are more specifically associated to important effects of the drug, including neural plasticity. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID- 22063718 TI - Cannabinoid facilitation of behavioral and biochemical hedonic taste responses. AB - Cannabinoid receptor agonists are known to stimulate feeding in humans and animals and this effect is thought to be related to an increase in food palatability. On the other hand, highly palatable food stimulates dopamine (DA) transmission in the shell of the nucleus accumbens (NAc) and this effect undergoes one trial habituation. In order to investigate the relationship between the affective properties of tastes and the response of NAc shell DA we studied the effect of delta-9-tetrahydrocannabinol (THC) on behavioral taste reactivity to intraoral infusion of appetitive (sucrose solutions) and aversive (quinine and saturated NaCl solutions) tastes and on the response of in vivo DA transmission in the NAc shell to intraoral sucrose. Rats were implanted with intraoral cannulae and the effect of systemic administration of THC on the behavioral reactions to intraoral infusion of sucrose and of quinine or saturated NaCl solutions were scored. THC increased the hedonic reactions to sucrose but did not affect the aversive reactions to quinine and NaCl. The effects of THC were completely blocked by the CB1 receptor inverse agonist/antagonist rimonabant given at doses that do not affect taste reactivity to sucrose. In rats implanted with microdialysis probes and with intraoral cannulae, THC, made sucrose effective in raising dialysate DA in the shell of the NAc. As in the case of highly palatable food (Fonzies, sweet chocolate), the stimulatory effect of sucrose on shell DA under THC underwent one trial habituation. Altogether, these findings demonstrate that stimulation of CB1 receptors specifically increases the palatability of hedonic taste without affecting that of aversive tastes. Consistent with the ability of THC to increase sucrose palatability is the observation that under THC pretreatment sucrose acquires the ability to induce a release of DA in the shell of the NAc and this property undergoes adaptation after repeated exposure to the taste (habituation). This article is part of a Special Issue entitled 'Central Control of Food Intake'. PMID- 22063719 TI - Central control of thermogenesis. AB - In mammals and birds, conservation of body heat at around 37 degrees C is vital to life. Thermogenesis is the production of this heat which can be obligatory, as in basal metabolic rate, or it can be facultative such as the response to cold. A complex regulatory system has evolved which senses environmental or core temperature and integrates this information in hypothalamic regions such as the preoptic area and dorsomedial hypothalamus. These areas then send the appropriate signals to generate and conserve heat (or dissipate it). In this review, the importance of the sympathetic nervous system is discussed in relation to its role in basal metabolic rate and adaptive thermogenesis with a particular emphasis to human obesity. The efferent sympathetic pathway does not uniformly act on all tissues; different tissues can receive different levels of sympathetic drive at the same time. This is an important concept in the discussion of the pharmacotherapy of obesity. Despite decades of work the medicine chest contains only one pill for the long term treatment of obesity, orlistat, a lipase inhibitor that prevents the absorption of lipid from the gut and is itself not systemically absorbed. The central controlling system for thermogenesis has many potential intervention points. Several drugs, previously marketed, awaiting approval or in the earlier stages of development may have a thermogenic effect via activation of the sympathetic nervous system at some point in the thermoregulatory circuit and are discussed in this review. If the balance is weighted to the "wrong" side there is the burden of increased cardiovascular risk while a shift to the "right" side, if possible, will afford a thermogenic benefit that is conducive to weight loss maintenance. This article is part of a Special Issue entitled 'Central Control Food Intake' PMID- 22063720 TI - StarD7 behaves as a fusogenic protein in model and cell membrane bilayers. AB - StarD7 is a surface active protein, structurally related with the START lipid transport family. So, the present work was aimed at elucidating a potential mechanism of action for StarD7 that could be related to its interaction with a lipid-membrane interface. We applied an assay based on the fluorescence de quenching of BD-HPC-labeled DMPC-DMPS 4:1 mol/mol SUVs (donor liposomes) induced by the dilution with non-labeled DMPC-DMPS 4:1 mol/mol LUVs (acceptor liposomes). Recombinant StarD7 accelerated the dilution of BD-HPC in a concentration dependent manner. This result could have been explained by either a bilayer fusion or monomeric transport of the labeled lipid between donor and acceptor liposomes. Further experiments (fluorescence energy transfer between DPH-HPC/BD HPC, liposome size distribution analysis by dynamic light scattering, and the multinuclear giant cell formation induced by recombinant StarD7) strongly indicated that bilayer fusion was the mechanism responsible for the StarD7 induced lipid dilution. The efficiency of lipid dilution was dependent on StarD7 electrostatic interactions with the lipid-water interface, as shown by the pH- and salt-induced modulation. Moreover, this process was favored by phosphatidylethanolamine which is known to stabilize non-lamellar phases considered as intermediary in the fusion process. Altogether these findings allow postulate StarD7 as a fusogenic protein. PMID- 22063721 TI - Opposing roles of connexin43 in glioma progression. AB - Despite the tremendous amount of data over the last 40years, lack of gap junctional intercellular communication (GJIC) or altered expression of gap junction proteins is still a lesser known 'hallmark' of cancer. Expression of astrocytic gap junction protein, connexin43 (Cx43), is often reduced in astrocytomas, the most common neoplasia of the central nervous system (CNS) in adults. Supported by a number of evidences, the global decrease of Cx43 expression appears to be advantageous for the growth of glioma cells. Although the mechanisms by which Cx43 regulates the expression levels of proteins involved in cell growth is unclear, there are evidences to suggest that it might be independent of their channel forming properties. In this regard, the carboxyl tail of Cx43 may have the ability to control the translocation of transcription factor regulators into the nucleus. However, this putative tumor suppressor effect of Cx43 is counterbalanced by its capacity to enhance the migration of glioma cells out of the tumor core through mechanisms that seems to implicate its carboxyl tail, possibly by interacting with the actin cytoskeleton. This ambivalence between the tumor suppressor effect and promotion of cell migration may partly be explained by the heterogeneous expression of Cx43 in the glioma core especially at the malignant glioblastoma stage; some tumor cells would be expected to migrate (Cx43 expressing cells) and others to proliferate (non expressing Cx43 cells). Moreover, the involvement of Cx43 in glioma progression seems to be more complex since, in addition, GJIC may increase their resistance to apoptosis and Cx43 may also affect cell homeostasis in a paracrine fashion via hemichannel action. In conclusion, Cx43 appears to be involved at different levels of the glioma progression by acting on cell growth regulation, promotion of cell migration and resistance to apoptosis. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics. PMID- 22063722 TI - The role of membrane thickness in charged protein-lipid interactions. AB - Charged amino acids are known to be important in controlling the actions of integral and peripheral membrane proteins and cell disrupting peptides. Atomistic molecular dynamics studies have shed much light on the mechanisms of membrane binding and translocation of charged protein groups, yet the impact of the full diversity of membrane physico-chemical properties and topologies has yet to be explored. Here we have performed a systematic study of an arginine (Arg) side chain analog moving across saturated phosphatidylcholine (PC) bilayers of variable hydrocarbon tail length from 10 to 18 carbons. For all bilayers we observe similar ion-induced defects, where Arg draws water molecules and lipid head groups into the bilayers to avoid large dehydration energy costs. The free energy profiles all exhibit sharp climbs with increasing penetration into the hydrocarbon core, with predictable shifts between bilayers of different thickness, leading to barrier reduction from 26 kcal/mol for 18 carbons to 6 kcal/mol for 10 carbons. For lipids of 10 and 12 carbons we observe narrow transmembrane pores and corresponding plateaus in the free energy profiles. Allowing for movements of the protein and side chain snorkeling, we argue that the energetic cost for burying Arg inside a thin bilayer will be small, consistent with recent experiments, also leading to a dramatic reduction in pK(a) shifts for Arg. We provide evidence that Arg translocation occurs via an ion induced defect mechanism, except in thick bilayers (of at least 18 carbons) where solubility-diffusion becomes energetically favored. Our findings shed light on the mechanisms of ion movement through membranes of varying composition, with implications for a range of charged protein-lipid interactions and the actions of cell-perturbing peptides. This article is part of a Special Issue entitled: Membrane protein structure and function. PMID- 22063723 TI - Medicinal plants used in Hmong women's healthcare in northern Thailand. AB - ETHNOPHARMACOLOGICAL RELEVANCE: We studied traditional knowledge of medicinal plants used for women's healthcare in three Hmong villages in northern Thailand and determined how prevalent such knowledge is. We documented traditional medical practices and determined which of the species used are culturally important among the Hmong. MATERIALS AND METHODS: We interviewed six key informants and 147 non specialist informants about their traditional knowledge of medicinal plants used in Hmong women's healthcare. We selected nine species that were known in all three villages as the domain for questionnaire interviews with 181 additional and randomly selected non-specialist informants. We calculated the Cultural Importance index (CI) for each species and use category. We tested normality of the data, age correlations, and gender correlations with Kolmogorov-Smirnov tests, Spearman's rank correlation coefficient, Kruskal-Wallis test, and Mann Whitney tests. RESULTS: We documented traditional knowledge of 79 medicinal plants used in women's healthcare. Of these, three species were culturally important to the Hmong. Our questionnaire interviews revealed significant difference in traditional medicinal plant knowledge between genders and age groups. CONCLUSIONS: The Hmong people in northern Thailand possess large amounts of traditional knowledge related to women's healthcare and plants used for this purpose. However, this knowledge, even for the culturally important species, is not possessed by all Hmong and there were signs of knowledge erosion. Preservation of the Hmong intellectual heritage related to medicinal plants used in women's healthcare requires intensive traditional knowledge dissemination to the young Hmong generation. PMID- 22063724 TI - Khat (Catha edulis) alters the phenotype and anti-microbial activity of peripheral blood mononuclear cells. AB - AIMS OF STUDY: The habit of khat chewing has been associated with increased risk of systemic and oral disease. Although research has been conducted on the affects of khat on oral epithelial cells, little is known about its influence on immune cells. This study examined the biological effects of khat on the phenotype and function of peripheral blood mononuclear cells (PBMCs). MATERIAL AND METHODS: Khat-stimulated PBMCs were examined for signs of cytotoxicity, apoptosis and changes in cell surface receptor and cytokine expression. Khat-induced regulation of transcription factors and stress-related factors were examined, as was PBMC phagocytic activity against oral bacteria. RESULTS: Khat was cytotoxic to PBMC in a dose- and time-dependent manner and cell death was mediated by apoptosis. Khat treated PBMC showed increased expression of co-stimulatory molecules (CD80, CD86 and MHC II) and pattern recognition receptors (TLR-2, TLR-4 and TREM-1) but secretion of inflammatory cytokines (TNFalpha, IL-6, CCL5, CXCL8) was inhibited. In contrast, khat induced an increase in the anti-inflammatory cytokine IL-10 as well as IL-2, IFN-gamma, FasL and HSP70. These khat-induced alterations were accompanied by increased expression of transcription factors p38 MAPK and HIF 1alpha, whilst expression of NFkappaB p65 was inhibited. Although the ability of PBMC to phagocytose dextran and oral bacteria was inhibited, production of reactive oxygen species was increased. CONCLUSION: These data suggest that khat may severely influence the effectiveness of immune surveillance and anti microbial capacity of PBMCs. PMID- 22063725 TI - Identification of hypoglycaemic compounds from berries of Juniperus oxycedrus subsp. oxycedrus through bioactivity guided isolation technique. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Decoction of Juniperus oxycedrus subsp. oxycedrus L. (Cupressaceae) berries is used internally as tea and pounded fruits are consumed to lower blood glucose levels in Turkey. AIM OF THE STUDY: To evaluate hypoglycaemic and antidiabetic activity of J. oxycedrus subsp. oxycedrus berries and to identify active compounds through bioactivity guided isolation technique. MATERIAL AND METHODS: Hypoglycaemic effect of J. oxycedrus subsp. oxycedrus (Joso) berry extracts on oral administration was studied using in vivo models in normal, glucose-hyperglycaemic rats. Streptozotocin induced diabetic rats were used to examine antidiabetic activity of Joso extracts, subextracts, fractions, subfractions and shikimic acid (SA). RESULTS: Through in vivo bioactivity-guided fractionation processes, shikimic acid, 4-O-beta-d-glucopyranosyl ferulic acid and oleuropeic acid-8-O-beta-d-glucopyranoside were isolated from the n-butanol subextract by silica gel and reverse phase column chromatography as the main active ingredient of the active subfraction. After 8 days administration of the major compound shikimic acid, blood glucose levels (24%), malondialdehyde levels in kidney tissues (63-64%) and liver enzymes (AST, ALT, ALP) of diabetic rats were decreased. CONCLUSION: Results indicated that Joso berry extract and its active constituents might be beneficial for diabetes and its complications. PMID- 22063726 TI - A novel property of propolis (bee glue): anti-pathogenic activity by inhibition of N-acyl-homoserine lactone mediated signaling in bacteria. AB - ETHNOPHARMACOLOGICAL RELEVANCE: An alternative approach to antibiotics is the development of anti-pathogenic agents to control the bacterial virulome. Such anti-pathogenic agents could target a phenomena known as quorum sensing (QS). MATERIALS AND METHODS: Six bacterial N-acyl-homoserine lactone (AHL)-dependent bioreporter strains were used to evaluate if bee hive glue also known as propolis contains constituents capable of inhibiting QS-controlled AHL signaling. In addition, the effect of propolis on the QS-dependent swarming motility was evaluated with the opportunisitic pathogen, Pseudomonas aeruginosa. RESULTS: Differences in the propolis tincture samples were identified by physiochemical profiles and absorption spectra. Propolis tinctures at 0.0005% (v/v) that do not affect bacteria biosensor growth or the reporter system monitored were exposed to biosensors with and without the addition an AHL. No AHL signal mimics were found to be present in the propolis tinctures. However, when propolis and an inducer AHL signal were together exposed to five Escherichia coli and a Chromobacterium violaceum biosensor, propolis disrupted the QS bacterial signaling system in liquid- and agar-based bioassays and in C(18) reverse-phase thin-layer plate assays. Swarming motility in the opportunistic pathogen, Pseudomonas aeruginosa PAO1 and its AHL-dependent LasR- and RhlR-based QS behaviors were also inhibited by propolis. CONCLUSIONS: Together, we present evidence that propolis contain compounds that suppress QS responses. In this regard, anti-pathogenic compounds from bee harvested propolis could be identified and isolated and thus will be valuable for the further development of therapeutics to disrupt QS signaling systems which regulate the virulome in many pathogenic bacteria. PMID- 22063727 TI - Effects of Lecythis pisonis Camb. (Lecythidaceae) in a mouse model of pruritus. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Lecythis pisonis Camb. (Lecythidaceae), is popularly known as "Sapucaia". In traditional medicine, leaves are used for the treatment of pruritus. AIM OF THE STUDY: The present study is aimed to investigate the antipruritic effect of the ethanol extract from leaves of Lecythis pisonis (LPEE), fractions (hexane-LPHF, ether-LPEF and ethyl acetate LPEAF) and mixture of triterpenes [ursolic and oleanolic acids (MT)] in mice and rats. MATERIALS AND METHODS: The LPEE, LPHF, LPEF, LPEAF and MT were evaluated on scratching behavior induced by compound 48/80 in mice. In addition, LPEE, LPEF and MT were investigated on rat peritoneal mast cells degranulation induced by compound 48/80 (ex vivo study). The anti-inflammatory activity of LPEE and LPEF was investigated in rats using carrageenan-induced hind paw edema model. In the evaluation of the spontaneous motor activity, the LPEE was studied for its effect on spontaneous motor activity in an open-field test in mice. RESULTS: The scratching behavior induced by compound 48/80 was significantly inhibited in mice pretreated with LPEE, LPHF, LPEF, LPEAF and MT. The suppressive effect of LPEE, LPEF and MT was only partially antagonized by naloxone. In addition, the compound 48/80-elicited degranulation of rat peritoneal mast cells was also markedly reduced in animals pretreated with LPEE, LPEF and MT. In the anti-inflammatory test, LPEE decreased the paw edema at the third hour after carrageenan (Carr) administration. Moreover, LPEF also was able to inhibit the oedematogenic response evoked by carr at all analysed time points. In the open-field test, LPEE pretreated mice showed no impairment of spontaneous locomotion. Furthermore, the LPEE demonstrated no overt toxicity up to an oral dose of 2g/kg in an acute toxicity assay. CONCLUSIONS: These results clearly indicate the antipruritic effects of Lecythis pisonis leaves and suggest that this effect may be related to a stabilizing action on mast cell membrane. Furthermore, these data support the traditional use of this plant against cutaneous pruritus. PMID- 22063728 TI - A new way to analyze resuscitation quality by reviewing automatic external defibrillator data. AB - AIMS: High quality cardiopulmonary resuscitation (CPR) plays an important role in survival of out-of-hospital cardiac arrests (OHCAs). We have developed an algorithm to automatically identify the quality of chest compressions from data retrieved from automatic external defibrillators (AEDs). METHODS: Electrocardiographic (ECG) signals retrieved from AEDs were analyzed by a newly developed algorithm to identify fluctuations in CPR. The algorithm contained three steps. First, it decomposed the AED signals into several intrinsic mode fluctuations (IMFs) by empirical mode decomposition (EMD). Second, it identified the dominant IMFs that carried the chest compression signals and weighted the IMFs to both enhance the chest compression oscillations and filter the noise. Third, it calculated the autocorrelation function (ACF) of the reconstructed signals and tested their periodicity. Using this algorithm, several CPR quality indicators were automatically calculated minute-by-minute and compared with those derived by audio and visual review of AED data by experienced physicians. RESULTS: A total of 77 (29 women, 48 men) OHCA patients were enrolled, and 351 one-min segments were analyzed. The results showed that the CPR quality parameters calculated from the algorithm were highly correlated with those from the manual review (all P<0.001). The limits of agreement by Bland-Altman analysis were acceptable for chest compression number, total flow time, and no flow time, but not for CPR rate. We also demonstrated that only 41.8+/-29.8% of time was spent in chest compressions and only 7.5+/-16.8% was spent in adequate chest compressions. CONCLUSION: Our results demonstrated that several indicators of CPR quality can be precisely and automatically determined by analyzing the ECG signals from AEDs using EMD and autocorrelograms. PMID- 22063730 TI - Histopathologic patterns of nervous system tumors based on computer vision methods and whole slide imaging (WSI). AB - BACKGROUND: Making an automatic diagnosis based on virtual slides and whole slide imaging or even determining whether a case belongs to a single class, representing a specific disease, is a big challenge. In this work we focus on WHO Classification of Tumours of the Central Nervous System. We try to design a method which allows to automatically distinguish virtual slides which contain histopathologic patterns characteristic of glioblastoma--pseudopalisading necrosis and discriminate cases with neurinoma (schwannoma), which contain similar structures--palisading (Verocay bodies). METHODS: Our method is based on computer vision approaches like structural analysis and shape descriptors. We start with image segmentation in a virtual slide, find specific patterns and use a set of features which can describe pseudopalisading necrosis and distinguish it from palisades. Type of structures found in a slide decides about its classification. RESULTS: Described method is tested on a set of 49 virtual slides, captured using robotic microscope. Results show that 82% of glioblastoma cases and 90% of neurinoma cases were correctly identified by the proposed algorithm. CONCLUSION: Our method is a promising approach to automatic detection of nervous system tumors using virtual slides. PMID- 22063729 TI - Passage of low-density lipoproteins through Bruch's membrane and choroid. AB - Plasma lipoproteins are thought to transport cholesterol, vitamins and carotenoids to the retinal pigment epithelium (RPE) for ultimate use by the photoreceptors. However, to reach the RPE, these lipoprotein particles must cross Bruch's membrane. We examined the reflection coefficient of Bruch's membrane (BrM) to low-density lipoprotein (LDL). Bruch's membrane and choroid were removed from 47 bovine eyes. Specimens were placed in a Ussing chamber and perfused with phosphate-buffered saline (PBS) with (31 specimens) or without (16 specimens) fluorescent low-density lipoproteins (DiI-LDL). The hydraulic conductivity of the tissue was determined for both calf and cow eyes. In the perfusions with DiI-LDL, the fluorescence intensity emitted by DiI-LDL in the efflux was measured and the reflection coefficient of BrM/choroid preparations to DiI-LDL determined. Leakage tests were done to confirm tissue integrity. Several specimens were examined using scanning electron microscopy (SEM) to examine tissue integrity before and after perfusion. Leak testing confirmed that BrM was intact both before and after perfusion. The average hydraulic conductivity of BrM/choroid perfusion of calf eyes with PBS alone was 1.42 +/- 0.55 * 10(-9) m/s/Pa (mean +/- SD, n = 11). The average hydraulic conductivity of the cow eyes was 4.94 +/- 1.48 * 10(-10) m/s/Pa (n = 5), nearly a 3-fold decrease with age. While the flow rate remained constant during the PBS perfusions, it decreased as a function of time during perfusion with DiI-LDLs. Our major finding was of fluorescence in the effluent collected in all perfusions with DiI-LDLs, demonstrating passage of LDL through the tissue. The average reflection coefficient of calf BrM/choroid preparations to DiI-LDL was 0.58 +/- 0.25 (n = 23); a similar distribution of reflection coefficients was seen in tissue from cow eyes (0.51 +/- 0.33, n = 8). Our data suggested that the DiI-LDL was modestly hindered and/or captured by the tissue. This might explain the progressive decrease of hydraulic conductivity with continued perfusion of DiI-LDL. PMID- 22063731 TI - An ultra-high speed whole slide image viewing system. AB - BACKGROUND: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed. METHOD: A prototype WSI viewer based on PlayStation(r)3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course. RESULTS: Pathologists were being able to use the system comfortably after 0-15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out. CONCLUSIONS: The preliminary results of adapting the Sony PlayStation(r)3 (PS3(r)) as an ultra high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice. PMID- 22063732 TI - Contemporary trends in procedural volume for adult facial trauma, 1996-2006. AB - OBJECTIVES: To determine how rates of operative facial fractures may have changed between 1996 and 2006 and to determine the potential impact of such change on otolaryngology residency surgical key indicator cases. STUDY DESIGN: Historical cohort study. SETTING: Academic medical center. SUBJECTS AND METHODS: The National Hospital Discharge Survey (NHDS) and National Survey of Ambulatory Surgery (NSAS) 1996 and 2006 cases were reviewed, extracting all cases of adult nasal, malar/zygomatic, maxillary, and mandibular fracture reductions in inpatient and outpatient settings, respectively. Procedure rates for each facial fracture were tabulated and compared between 1996 and 2006. RESULTS: Overall in 1996, there were an estimated 113,041 +/- 3740 operative facial fracture repairs performed. Among the 3 key indicator fracture repairs most relevant to otolaryngologists, there were 15,810 +/- 2143 open nasal fracture reductions, 9360 +/- 1742 open zygomaticomaxillary (ZMC) fracture reductions, and 20,214 +/- 2585 open mandibular fracture repairs. Overall in 2006, there were 120,463 +/- 7554 total facial fracture procedures, with 11,613 +/- 2846 open nasal fracture reductions, 10,216 +/- 2881 open ZMC fracture reductions, and 17,965 +/- 3171 open mandibular repairs. Comparing cohorts, there was no significant change in number of open nasal, ZMC, or mandibular fracture repairs (P = .24, P = .58, P = .80, respectively). CONCLUSION: Facial fracture procedure rates have remained largely stable over the past 10 years. These data have implications for otolaryngology training programs and could help guide resident education in facial trauma. PMID- 22063733 TI - Lateral nasal artery pedicled island flap for repair of nasal alar defects. PMID- 22063734 TI - Determining the most suitable costal cartilage level for rhinoplasty: an experimental study. AB - OBJECTIVE: The aim of this study was to compare the biomechanical properties of septal cartilage (SC) and costal cartilage (CC) grafts harvested from different ribs and to find at which level CC has characteristics closest to SC. STUDY DESIGN: Experimental cadaver study. SETTING: Istanbul Training and Research Hospital. MATERIAL AND METHOD: Cartilage grafts were harvested from the 6th, 7th, and 8th ribs and the SC of 10 fresh cadavers. Shaped cartilage grafts were subjected to a bending test. Results were measured, and the force-deflection curve was plotted. Flexural strength (sigma(f)) and flexural modulus of elasticity (E(f)) were determined. Fractured surfaces were evaluated by scanning electron microscopy (SEM). RESULTS: According to F(max), it was determined that ribs 6, 7, and 8 have significantly more durability compared with the SC (Ps = .030, .004, and .001). With regard to deflection, there was no significant difference between the SC and the 6th and 7th ribs and between the 6th and 7th ribs (Ps = 1.000, .088, and .306), while a significant difference was found between the SC and the 8th rib (P = .001). According to sigma(f), no differences were seen between the 6th and 7th rib (P = .782), while difference was detected between the 6th and 8th and the 7th and 8th ribs (p = .001). Similar trends were established in E(f) values as in sigma(f.) These results were confirmed by SEM images. CONCLUSION: The 7th CC can be used as autograft because it shows similar properties to SC. However, the 6th CC is preferred if more flexibility is desired, and the 8th CC is preferred where more strength is needed. PMID- 22063735 TI - Long-term effect of prednisolone on functional blink recovery after transient peripheral facial motor paralysis. AB - OBJECTIVE: To determine the functional recovery in patients with severe transient peripheral facial motor paralysis (Bell palsy). STUDY DESIGN: Prospective controlled trial. SETTING: Academic medical center. SUBJECTS AND METHODS: Blink recovery was studied in 2 groups of severely affected Bell palsy patients during a follow-up period of 84 weeks. The patients in one group received prednisolone within the first week after the onset of symptoms. No medication was given to the other group. A control group of healthy subjects was also included. Simultaneous orbicularis oculi muscle activity and eyelid kinematics were recorded by surface electromyographic (EMG) recording and eyelid search coils, respectively. RESULTS: At the beginning of the paralysis, very little integrated orbicularis oculi muscle activity and eyelid movement was measured at the palsied side of the face. Thirteen weeks later, the integrated orbicularis oculi EMG and functional blink recovery gradually improved until 39 weeks. Beyond, only the integrated orbicularis oculi EMG slightly increased. At 84 weeks, the integrated orbicularis oculi EMG was significantly larger in the prednisolone group compared with the control group. The integrated EMG of the nonmedicated group recovered to normal values. Curiously enough, the functional blink recovery at the palsied side remained reduced to 64% compared with the healthy controls in the prednisolone treated group and to 36% in the nonmedicated group. CONCLUSION: The authors demonstrate that prednisolone significantly increased the orbicularis oculi muscle activity and significantly improved functional blink recovery in severely affected Bell palsy patients. However, the increase of muscle activity was insufficient to restore functional blinking to normal values. PMID- 22063736 TI - Characteristics of inpatient thyroid surgery at US academic and affiliated medical centers. AB - OBJECTIVE: Describe data from patients undergoing thyroid surgeries for benign and malignant disease at US academic medical centers. STUDY DESIGN: Retrospective, database search. SETTING: The University Health System (UHC) Consortium (Oak Brook, Illinois) data compiled from discharge summaries. SUBJECTS AND METHODS: Discharge data were collected from the first quarter of 2002 through the fourth quarter of 2009. Searching strategy was based on diagnosis of thyroid disease and patients undergoing thyroid surgery across all UHC facilities. Demographic information was collected as well as length of stay (LOS) and costs. Complications were evaluated in this analysis. RESULTS: During the study period, 68,014 thyroidectomies were performed, with 27,200 for thyroid cancer. During the same period 6365 neck dissections were performed, with 1539 as stand-alone procedures. Total thyroidectomy was the procedure of choice for malignant disease. More total thyroidectomies and fewer hemithyroidectomies were being performed for benign thyroid disease in the inpatient setting. Almost all postoperative complications were more frequent after surgery for cancer except myocardial infarction and aspiration pneumonia. On average, LOS was longer for benign disease, but costs were higher for malignant disease. CONCLUSION: This is the largest series reporting inpatient LOS and mortality for thyroid surgery. The limitation of this study is that it reports patients whose stays were more than 23 hours, leaving out a significant number of thyroid surgeries that are performed as outpatients. Although the results contribute greatly to characterizing inpatient surgery, the results may not reflect current US trends for thyroid surgery. PMID- 22063737 TI - Anti-inflammatory potential of an ethyl acetate fraction isolated from Justicia gendarussa roots through inhibition of iNOS and COX-2 expression via NF-kappaB pathway. AB - Justicia gendarussa Burm.f. (J. gendarussa) is a plant used as traditional medicine in different parts of India and China to treat inflammatory disorders like rheumatoid arthritis. But its mechanism of anti-inflammatory action is still unclear. Hence in this context, the objective of our study is to reveal the mechanism of anti-inflammatory activity of J. gendarussa which would form an additional proof to the traditional knowledge of this plant. The anti inflammatory function and mechanism(s) of action was studied in an ethyl acetate fraction isolated from methanolic extract of J. gendarussa roots (EJG). Anti inflammatory studies were conducted on rats using partitioned fractions isolated from methanolic extract of J. gendarussa roots. In carrageenan-induced rat paw edema, ethyl acetate fraction brought about 80% and 93% edema inhibition at 3rd and 5th hour at a dose of 50 mg/kg, when compared to other extracts and Voveran. We investigated whether EJG inhibits the release of cycloxygenase (COX), 5 lipoxygenase (5-LOX), interleukin-6 (IL-6) and nuclear factor kappa B (NF-kappaB) in LPS stimulated human peripheral blood mononuclear cells (hPBMCs). Results shows that EJG dose dependently inhibited LPS-activated COX, 5-LOX, IL-6, and NF kappaB in hPBMCs. EJG also reduced LPS induced levels of iNOS and COX-2 mRNA expression in hPBMCs. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory activity of EJG and therefore, we report the first confirmation of the anti-inflammatory potential of this traditionally employed herbal medicine in vitro. PMID- 22063739 TI - 50(th) International Congress of Meat Science and Technology (50th ICoMST) Helsinki, Finland, 8-13 August 2004. PMID- 22063738 TI - Deficiency in TLR2 but not in TLR4 impairs dendritic cells derived IL-10 responses to schistosome antigens. AB - The purpose of this study was to observe the diverse functions of Toll-like receptors (TLRs) in responses to specific schistosome antigens. Bone marrow derived dendritic cells (BMDCs) from TLR2-deficient (TLR2(-/-)) or TLR4-deficient (TLR4(-/-)) mice were activated with soluble schistosomule antigen (SSA) or soluble egg antigen (SEA). TLR2 mRNA expression was significantly increased in B6 BMDCs following SEA stimulation. TLR2-deficient BMDCs showed enhanced MHCII expression following SSA and SEA stimulation. TLR2-deficient but not TLR4 deficient BMDC failed to produce IL-12p70 and IL-10 in response to schistosome antigens. TLR2-deficient BMDCs induced a stronger CD4(+) T cell proliferative response. IL-4 and IL-10 expression was inhibited in CD4(+) T cells primed with TLR2-deficient BMDCs, while enhanced in TLR4-deficient BMDCs-primed CD4(+) T cells. These results suggest that TLR2 is essential for the establishment of the DC production of IL-12p70 and IL-10. PMID- 22063740 TI - Greetings of the first European meeting of meat research workers. PMID- 22063741 TI - Quality pork genes and meat production. AB - Functional genomics, including analysis of the transcriptome and proteome, provides new opportunities for understanding the molecular processes in muscle and how these influence its conversion to meat. The Quality Pork Genes project was established to identify genes associated with variation in different aspects of raw material (muscle) quality and to then develop genetic tools that could be utilized to improve this quality. DNA polymorphisms identified in the porcine PRKAG3 and CAST genes illustrate the impact that such tools can have in improving meat quality. The resources developed in Quality Pork Genes provide the basis for identifying more of these tools. PMID- 22063742 TI - Carbohydrate metabolism in meat animals. AB - Oxidative energy production is by far dominant in living animal muscles, with the exception the short periods of severe stress, where the aerobic capacity is exceeded, and formation of large amounts of lactate and protons will take place. Energy consumption in muscle cells continues post-mortem with formation of large amounts of lactate and protons, because the aerobic processes for energy production are not available. Post-mortem, the fall in pH is delayed only by buffering capacity of the muscle fibres. In living animals, in addition to buffering capacity, both respiration and transport of lactate and protons out of the muscle fibres by monocarboxylate transporters participate in the regulation of muscle fibre pH which never falls as low as the ultimate pH of the meat. Understanding the regulation of pH in muscle is important both for the welfare of living animals and from the technological point of view as a factor influencing meat quality. PMID- 22063743 TI - Intramuscular connective tissue and its role in meat quality. AB - The amount, spatial distribution and composition of the connective tissue within muscle vary with muscle position in the carcase and with animal age. This has long been recognised to influence the tenderness of cooked meat. This paper builds upon some historical perspectives with a review of some recent clarifications of the biological function of intramuscular connective tissue (IMCT) and of its contribution to meat texture, which is clearly multifactorial. The perimysial component of IMCT varies most in amount between muscles and is also the IMCT structure most involved in defining the mechanical integrity of cooked meat. The distribution of perimysium defines muscle fascicle size (muscle "grain" size), which is also still regarded as an indicator of tenderness. Postmortem conditioning of meat has consistently been shown to reduce the strength of intramuscular connective tissue in the raw state, but with equal consistency, this has been shown not to affect the toughness of cooked meat. Cooking increases IMCT strength in the range 20-50 degrees C and decreases its contribution at higher temperatures and longer cooking times. Crosslinking of collagen in older animals is generally considered to result in tougher meat, although definitive links between mature crosslink content and cooked meat toughness have been difficult to prove. In the last quarter-century, IMCT has been increasingly viewed as a "background" contributor to meat texture, which is difficult to change. However, the large variation in perimysial content of muscles in one animal represents an incredible range of expression. This appears to be firmly fixed to the functional properties of different muscles. In particular, it is hypothesised that definition of muscle fascicle size and shape by the bounding perimysium is related to the need for sub-sections of the whole muscle to slip past each other in the normal contractile function of the tissue. Despite this, the amounts and composition of IMCT can be manipulated by animal nutrition and exercise, and factors affecting the turnover of IMCT may especially be a future target for manipulation of meat texture. PMID- 22063744 TI - The chilling of carcasses. AB - Biochemical processes and structural changes that occur in muscle during the first 24h postmortem play a great role in the ultimate quality and palatability of meat and are influenced by the chilling processes that carcasses are subjected to after slaughter. For beef and lamb, employing chilling parameters that minimize cold shortening is of greatest importance and can be best addressed by ensuring that muscle temperatures are not below 10 degrees C before pH reaches 6.2. For pork, because of the impact of high muscle temperatures and low pH on the development of pale, soft, and exudative (PSE) pork, a more rapid chilling process is needed to reduce PSE with the recommended internal muscle temperature of 10 degrees C at 12h and 2-4 degrees C at 24h. Spray chilling, a system whereby chilled water is applied to carcasses during the early part of postmortem cooling, is used to control carcass shrinkage and to improve chilling rates through evaporative cooling. Delayed chilling can be used to reduce or prevent the negative effects of cold shortening; however, production constraints in high volume facilities and food safety concerns make this method less useful in commercial settings. Electrical stimulation and alternative carcass suspension programs offer processors the opportunity to negate most or all of the effects of cold shortening while still using traditional chilling systems. Rapid or blast chilling can be an effective method to reduce the incidence of PSE in pork but extreme chilling systems may cause quality problems because of the differential between the cold temperatures on the outside of the carcass compared to the warm muscle temperatures within the carcass (i.e., muscles that are darker in color externally and lighter in color internally). PMID- 22063745 TI - The safety of pasteurised in-pack chilled meat products with respect to the foodborne botulism hazard. AB - There has been a substantial increase in sales of pasteurised in-pack chilled products over the last decade. It is anticipated that this trend will continue. These foods address consumer demand in being of high quality and requiring little preparation time. The microbiological safety of these foods commonly depends on a combination of a minimal heat treatment, refrigerated storage and a restricted shelf-life. The principal microbiological safety hazard for pasteurised in-pack meat products is foodborne botulism, as presented by non-proteolytic Clostridium botulinum. This review provides a summary of research that has contributed to the safe development of these foods without incidence of botulism. PMID- 22063746 TI - Microbiological ecology of marinated meat products. AB - Marinated meat products are consumed increasingly. In addition to taste, marinating has been considered to increase product safety and shelf life. In Finland, marinades are complex, spiced sauces. They are acidic water-oil emulsions typically containing salt, sugar, sorbate and/or benzoate. Marinated products are usually packaged under modified atmospheres. This results in the growth of psychrotrophic, anaerobic bacteria like lactic acid bacteria (LAB). Marinating did not increase the shelf life of Finnish poultry products and it strongly selected novel spoilage LAB. Surprisingly, it neither had inhibitory effect on Campylobacter. The buffering capability of meat neutralizes the acidic marinade and results in dissociation of the lipophilic acids making their antimicrobial effect nonexistent. PMID- 22063747 TI - Recent concerns about stunning and slaughter. AB - This review summarises information that is relevant to concerns that have recently been expressed about stunning and slaughter. It is known that captive bolt stunning can result in brain material passing to the lungs via the jugular veins. If future studies show that BSE prions pass beyond the lungs to the edible carcass, there will be a move away from captive bolt stunning in large cattle towards electrical stunning. Greater use of electrical stunning in large cattle will increase the importance of blood splash in the beef industry. The theoretical causes of blood splash are reviewed to improve our understanding of this problem. In some situations it can be due to excessive venous pressure causing rupture of a capillary bed some distance from the source of the pressure rise, but it is not known whether this applies to electrical stunning. Gas stunning is replacing electrical stunning for poultry because it can reduce blood spots, which is a similar condition to blood splash. Several gas stunning methods are now being used, but it is not clear which of these is the most humane. Anoxic stunning leads to carcass convulsions and this causes more carcass damage. In fish, recent developments in electrical stunning are showing promise in overcoming problems with carcass damage. It is recommended that rock lobsters should be chilled or frozen before butchery, to ensure a humane death. PMID- 22063748 TI - Effects of heat on meat proteins - Implications on structure and quality of meat products. AB - Globular and fibrous proteins are compared with regard to structural behaviour on heating, where the former expands and the latter contracts. The meat protein composition and structure is briefly described. The behaviour of the different meat proteins on heating is discussed. Most of the sarcoplasmic proteins aggregate between 40 and 60 degrees C, but for some of them the coagulation can extend up to 90 degrees C. For myofibrillar proteins in solution unfolding starts at 30-32 degrees C, followed by protein-protein association at 36-40 degrees C and subsequent gelation at 45-50 degrees C (conc.>0.5% by weight). At temperatures between 53 and 63 degrees C the collagen denaturation occurs, followed by collagen fibre shrinkage. If the collagen fibres are not stabilised by heat-resistant intermolecular bonds, it dissolves and forms gelatine on further heating. The structural changes on cooking in whole meat and comminuted meat products, and the alterations in water-holding and texture of the meat product that it leads to, are then discussed. PMID- 22063749 TI - Meat as a component of a healthy diet - are there any risks or benefits if meat is avoided in the diet? AB - Meat is frequently associated with a "negative" health image due to its "high" fat content and in the case of red meat is seen as a cancer-promoting food. Therefore, a low meat intake, especially red meat is recommended to avoid the risk of cancer, obesity and metabolic syndrome. However, this discussion overlooks the fact, that meat is an important source for some of micronutrients such as iron, selenium, vitamins A, B12 and folic acid. These micronutrients are either not present in plant derived food or have poor bioavailability. In addition, meat as a protein rich and carbohydrate "low" product contributes to a low glycemic index which is assumed to be "beneficial" with respect to overweight, the development of diabetes and cancer (insulin resistance hypothesis). Taken together meat is an important nutrient for human health and development. As an essential part of a mixed diet, meat ensures adequate delivery of essential micronutrients and amino acids and is involved in regulatory processes of energy metabolism. PMID- 22063750 TI - Meat fats in nutrition. AB - This article reviews the fat content and fatty acid composition of meats in the human diet and discusses nutritional facts related to meat, meat products and other meat-containing foods as sources of dietary fats. Meat is an increasingly important source of high-value animal protein worldwide. Meat fat comprises mostly monounsaturated and saturated fatty acids, with oleic (C18:1), palmitic (C16:0), and stearic acid (C18:0) being the most ubiquitous. Meat and meat products are considerable sources of cholesterol in the diet. In most industrialized countries, a high meat intake contributes to a higher than recommended total and saturated fat and cholesterol intake. Another concern is that meat may replace sources of other important nutrients in the diet. Therefore, the advice to consumers is to prefer lean meats and low-fat meat products and use meat in moderation only. PMID- 22063751 TI - Reducing sodium intake from meat products. AB - Sodium intake exceeds the nutritional recommendations in many industrialized countries. Excessive intake of sodium has been linked to hypertension and consequently to increased risk of stroke and premature death from cardiovascular diseases. The main source of sodium in the diet is sodium chloride. It has been established that the consumption of more than 6g NaCl/day/person is associated with an age-increase in blood pressure. Therefore, it has been recommended that the total amount of dietary salt should be maintained at about 5-6g/day. Genetically salt susceptible individuals and hypertensives would particularly benefit from low-sodium diets, the salt content of which should range between 1 and 3g/day. In industrialized countries, meat products and meat meals at home and in catering comprise one of the major sources of sodium, in the form of sodium chloride. Sodium chloride affects the flavour, texture and shelf life of meat products. The salt intake derived from meat dishes can be lowered by, whenever possible, adding the salt, not during preparation, but at the table. In most cases, salt contents of over 2% can be markedly lowered without substantial sensory deterioration or technological problems causing economical losses. Salt contents down to 1.4% NaCl in cooked sausages and 1.75% in lean meat products are enough to produce a heat stable gel with acceptable perceived saltiness as well as firmness, water-binding and fat retention. A particular problem with low-salt meat products is, however, that not only the perceived saltiness, but also the intensity of the characteristic flavour decreases. Increased meat protein content (i.e. lean meat content) in meat products reduces perceived saltiness. The required salt content for acceptable gel strength depends on the formulation of the product. When phosphates are added or the fat content is high, lower salt additions provide a more stable gel than in non-phosphate and in low-fat products. Small differences in salt content at the 2% level do not have marked effects on shelf life of the products. By using salt mixtures, usually NaCl/KCl, the intake of sodium (NaCl) can be further reduced. PMID- 22063752 TI - Feeding and meat quality - a future approach. AB - The continuous demand for high standards of quality assurance in the meat production of today and tomorrow calls for development of new tools capable of meeting such demands. The present paper aims to re-think the traditional way of using feeding as a quality control tool in the production of meat and to introduce the potential of a nutrigenomic approach as a first step in the development of pro-active quality control systems which fulfil future demands from industry and consumers. A few chosen examples present how specific feeding strategies can manipulate (i) muscle protein turnover and thereby meat tenderness as well as the cost and sustainability of the production and (ii) muscle energy levels at slaughter and thereby the pH decline, water-holding capacity and the sensory characteristics of meats. The examples are discussed in relation to exploiting essential and basic understanding of physiological and physical processes, which can subsequently be included in a systems biology line of thought of importance for development of unique decision support systems in future meat production. PMID- 22063753 TI - The future of BSE from the global perspective. AB - Although, the bovine spongiform encephalopathy (BSE) risk of most countries in Europe has been assessed and they have implemented both measures to control BSE and extensive surveillance systems, complete and valid data is still not consistently available. Globally, data is largely unavailable. Assessments based on incomplete or invalid information could lead to false conclusions. The BSE risk of countries throughout the world must continue to be assessed, and improvements in collection of surveillance data must be made, both in countries already reporting BSE cases and worldwide, in order to evaluate the global BSE picture and assure that cattle and products can be safely traded. PMID- 22063754 TI - Cyclosulfamide-based derivatives as inhibitors of noroviruses. AB - An optimization campaign focused on improving pharmacological activity and physicochemical properties of a recently-identified class of cyclosulfamide-based norovirus inhibitors has been carried out. Dimeric compound 4 was found to be a ~10-fold more potent norovirus inhibitor (ED(50) 0.4 MUM) compared to the original hit, however, isonipecotic acid ester derivatives 7e and 10a were shown to have superior therapeutic indices. PMID- 22063755 TI - Anti-AIDS agents 85. Design, synthesis, and evaluation of 1R,2R-dicamphanoyl-3,3 dimethyldihydropyrano-[2,3-c]xanthen-7(1H)-one (DCX) derivatives as novel anti HIV agents. AB - In this study, 1R,2R-dicamphanoyl-3,3-dimethydihydropyrano[2,3-c]xanthen-7(1H) one (DCX) derivatives were designed and synthesized as novel anti-HIV agents against both wild-type and non-nucleoside reverse transcriptase (RT) inhibitor resistant HIV-1 (RTMDR-1) strains. Twenty-four DCX analogs (6-29) were synthesized and evaluated against the non-drug-resistant HIV-1 NL4-3 strain, and selected analogs were also screened for their ability to inhibit the RTMDR-1 strain. Compared with the control 2-ethyl-3',4'-di-O-(-)-camphanoyl-2',2' dimethyldihydropyrano[2,3-f]chromone (2-EDCP, 2), one of the best anti-HIV coumarin derivatives in our prior study, three DCX compounds (7, 12, and 22) showed better activity against both HIV strains with an EC(50) range of 0.062 0.081 MUM, and five additional compounds (8, 11, 16, 18, and 21) exhibited comparable anti-HIV potency. Six DCX analogs (7, 11-12, 18, and 21-22) also showed enhanced selectivity index (SI) values in comparison to the control. Structure-activity relationship (SAR) information suggested that the extended conjugated system of the pyranoxanthone skeleton facilitates the interaction of the small DCX molecule within the viral binding pocket, consequently leading to enhanced anti-HIV activity and selectivity. Compared to DCP compounds, DCX analogs are a more promising new class of anti-HIV agents. PMID- 22063756 TI - Treatment of clavicle fractures: current concepts review. AB - Clavicle fractures are common in adults and children. Most commonly, these fractures occur within the middle third of the clavicle and exhibit some degree of displacement. Whereas many midshaft clavicle fractures can be treated nonsurgically, recent evidence suggests that more severe fracture types exhibit higher rates of symptomatic nonunion or malunion. Although the indications for surgical fixation of midshaft clavicle fractures remain controversial, they appear to be broadening. Most fractures of the medial or lateral end of the clavicle can be treated nonsurgically if fracture fragments remain stable. Surgical intervention may be required in cases of neurovascular compromise or significant fracture displacement. In children and adolescents, these injuries mostly consist of physeal separations, which have a large healing potential and can therefore be managed conservatively. Current concepts of clavicle fracture management are discussed including surgical indications, techniques, and results. PMID- 22063757 TI - Synthesis, characterization and comparison of antimicrobial activity of PEG/TritonX-100 capped silver nanoparticles on collagen scaffold. AB - Silver nanoparticles have received attention as novel antimicrobial agents. In order to study the effects of silver nanoparticles on both Gram positive and negative bacteria, the nanoparticles were synthesized via chemical reduction method using different concentrations (0.3, 0.6 and 0.9 mM) of poly(ethylene) glycol (PEG) and TritonX-100 (TX). Also, mixed PEG/TX systems with equimolar concentrations capped silver nanoparticles were synthesized and confirmed by UV vis, fluorescence spectroscopy and particle size analysis. These coated silver nanoparticles were incorporated into collagen, lyophilized to form scaffolds and characterized by SEM, XRD, ATR-FTIR, DSC, TGA and zeta potential. Results on mechanical property of all the scaffolds displayed no significant difference in the percentage elongation at break. However, the maximum percentage of 46.67% was observed with the combinations (0.9 mM PEG+0.9 mM TX). This implies that the combinations of surfactants increase the elasticity, which is useful for biomedical applications, e.g., heart-valve preparations. Furthermore, the antimicrobial activities of these capped silver nanoparticles homogenized with collagen were tested against both Gram positive and negative bacteria. Minimum inhibitory concentration values obtained for the combination (0.9 mM PEG+0.9 mM TX) were found to be better than others and thus provide strong antibacterial property to the collagen scaffolds prepared for tissue regeneration applications. PMID- 22063758 TI - A novel toxic alkaloid from poison hemlock (Conium maculatum L., Apiaceae): identification, synthesis and antinociceptive activity. AB - 2-Pentylpiperidine, named conmaculatin, a novel volatile alkaloid related to coniine was identified from the renowned toxic weed Conium maculatum L. (Apiaceae). The structure of conmaculatin was corroborated by synthesis (8 steps starting from cyclohexanol, overall yield 12%). Conmaculatin's strong peripheral and central antinociceptive activity in mice was observed in a narrow dose range (10-20mg/kg). It was found to be lethal in doses higher than 20mg/kg. PMID- 22063760 TI - American Pediatric Society 2011 Presidential Address: Earthquakes, tectonic shifts in graduate medical education, and the role of the APS in finding solid ground. PMID- 22063762 TI - Dissemination of central nervous system tissue from the brain and spinal cord of cattle after captive bolt stunning and carcass splitting. AB - In the absence of reliable live animal tests for the presence of BSE in cattle, a number of measures have been applied to exclude specified risk materials (SRM) from the human food chain. However, concerns remain that current practices in the stunning and slaughter of cattle may disseminate central nervous system (CNS) tissue to meat and meat contact surfaces. The objective of this study was to establish the particular risks of CNS tissue dissemination associated with captive bolt stunning and carcass splitting. The study applied enzyme linked immunosorbent assays (ELISAs) in the detection and quantification of two CNS proteins, syntaxin 1b and GFAP. The study observed extensive dispersal of both CNS proteins onto equipment, beef hide and personnel. These results demonstrate that despite the rigorous application of current SRM control policies, normal slaughter practices continue to present significant opportunities for CNS material including BSE prion present in the CNS of any sub-clinically infected cattle to contaminate meat entering the human food chain. PMID- 22063763 TI - Strategies to eliminate atypical flavours and aromas in sow loins. I. Optimization of sodium tripolyphosphate, sodium bicarbonate, and injection level. AB - Sow meat has been identified to possess objectionable atypical aromas and flavors we have termed as "sow taint". The objective of this study was to identify optimum concentrations of sodium bicarbonate (NaHCO(3)), sodium tripolyphosphate (PO(4)) and percentage marination solution that reduces or eliminates sow taint. Sow loins (N=20) with atypical aromas and flavors were treated with solutions containing sodium tripolyphosphate and sodium bicarbonate with concentrations ranging from 0.25 to 0.50% and 0.35 to 0.70 M, respectively. Injection levels (pump) ranged from 5 to 15% (wt./wt.). Marinated loin chops were evaluated for flavor and textural attributes by a trained sensory panel. Response surface methodology determined four optimum treatment combinations (15% pump, 0.5% PO(4), 0.70 M NaHCO(3); 15% pump, 0.25% PO(4), 0.70 M NaHCO(3); 15% pump, 0.25% PO(4), 0.35 M NaHCO(3); and 15% pump, 0.25% PO(4), 0.35 M NaHCO(3)) that reduced (P<0.05) metallic aroma, metallic and sour aftertastes, and detectable connective tissue while improving (P<0.05) muscle fiber tenderness, juiciness, and overall tenderness. PMID- 22063764 TI - Strategies to eliminate atypical aromas and flavors in sow loins-part II: consumer acceptance of loins marinated with sodium tripolyphosphate and sodium bicarbonate. AB - An identified challenge in using sow loins as a raw material for value added enhanced whole muscle products is to eliminate or minimize objectionable atypical aromas and flavors ("sow taint," ST) that may occur in some sow carcasses. The objective of this study was to determine consumer acceptance of sow loins exhibiting atypical aromas and flavors marinated with a solution of salt, sodium tripolyphosphate and sodium bicarbonate. Sow loins (N=34) with atypical aromas and flavors and commodity loins (N=6) were fabricated into anterior and posterior loin sections and marinated with one of four ST marinade treatment combinations (15% pump, 0.5% PO(4), 0.70 M NaHCO(3); 15% pump, 0.25% PO(4), 0.70 M NaHCO(3); 15% pump, 0.25% PO(4), 0.35 M NaHCO(3); and 15% pump, 0.25% PO(4), 0.35 M NaHCO(3)), or a control marinade (0.25% sodium tripolyphosphate, 15% injection level) and evaluated by a consumer sensory panel. Sensory ratings determined that ST loin chops injected with a 15% solution of sodium tripolyphosphate (0.50%) and sodium bicarbonate (0.35 M) were not different (P>0.05) than loin chops from marinated commodity control loin sections (N=12) for flavor, texture, juiciness, and overall acceptability. These results indicate that a solution containing sodium tripolyphosphate and sodium bicarbonate minimized the detection of atypical aromas and flavors in sow loins. PMID- 22063765 TI - Pore formation in cured-smoked pork determined with image analysis-effects of tumbling and RN(-) gene. AB - The objective of the present study was to investigate the effects of RN genotype (rn(+)/rn(+) or RN(-)/rn(+)) and tumbling condition (tumbled or non-tumbled) on the number of undesirable pore formation in cured-smoked loins using image analysis. Even when not significant, RN(-)/rn(+) loins contained more pores than rn(+)/rn(+) loins. Tumbling clearly decreased the total number of pores, but increased the mean area per pore. Tumbled rn(+)/rn(+) loins contained half the number of pores compared with tumbled RN(-)/rn(+) loins. Even if RN genotype and tumbling influenced the number of pores they did not explain the development of pores in processed meat. The high correlations found when comparing the image analysis results with data from a trained sensory panel and visually scored images indicate that image analysis is a good tool in this type of investigations. PMID- 22063766 TI - Meat quality, fatty acid composition and flavour analysis in Belgian retail beef. AB - The objective of this study was to evaluate the differences in biochemical, sensorial and quality characteristics of retail beef in Belgium. Four types of beef (Belgian Blue double-muscled, Limousin, Irish and Argentine) and two different muscles (longissimus lumborum and semimembranosus) were bought at the retail level and compared with regard to colour, shear force, collagen content, fatty acid analysis, taste panel evaluation as well as flavour analysis. Belgian Blue and Limousin beef had a paler colour, lower collagen and intramuscular fat contents. Fatty acid profiles were significantly different between the four types, with significantly higher PUFA/SFA and n-6/n-3 ratios for Belgiam Blue and Limousin beef compared to Argentine and Irish beef. There were significant differences between the meat types for taste panel tenderness and shear force, however both measurements did not fully correspond. Flavour analysis by gas chromatography-mass spectrometry as well as sensory analysis demonstrated that Irish and Argentine beef had a higher flavour intensity related to higher contents of volatile compounds. Differences in tenderness and flavour between the meat types were probably affected by differences in ageing time, related to import vs local production of meat. PMID- 22063767 TI - Physico-chemical characteristics of carcass and meat Manchego-breed suckling lambs slaughtered at different weights. AB - Forty-nine Manchego-breed lambs raised exclusively on their dams' milk until slaughter were used in this study. The effects of gender and slaughter weight (10, 12 and 14 kg) on carcass fatness, meat quality and the fatty acid composition of their fat were studied. Fatness, and in particular dorsal-fat thickness (P?0.01), increased with live weight. The effect of gender was even greater (P?0.001), as female lambs presented the highest fatness values for all parameters studied. The smallest drop in m. longissimus pH values was seen in the lowest-weight (10 kg) lambs. These same lambs displayed the highest L* value and thus the lightest colour. Fatty acid composition, which was not influenced by live weight, was affected by gender. The subcutaneous fat of female lambs contained more linolenic acid (C18:3) (P?0.01) and a greater proportion of polyunsaturated fatty acids than that of male lambs (P?0.001). Likewise, the intramuscular fat of female lambs displayed a greater proportion of monounsaturated fatty acids (P?0.001) than that of male lambs. PMID- 22063768 TI - Development of a polymerase chain reaction assay for species identification of goose and mule duck in foie gras products. AB - Polymerase chain reaction amplification of a conserved region of the alpha-actin gene has been used for the specific identification of goose (Anser anser) and mule duck (Anas platyrhynchos*Cairina moschata) foie gras. Universal primers were used for the amplification of a DNA fragment containing three introns and four exons of the alpha-actin gene in goose and mule duck. Sequence analysis of the amplified fragments was necessary for the design of forward species-specific primers in the goose and mule duck alpha-actin genes. The use of species-specific forward primers, together with a reverse universal primer, produced amplicons of different length, allowing clear identification of goose and mule duck foie gras samples. Analysis of experimental mixtures demonstrated that 1% of duck can be easily detected in goose foie gras using the PCR method developed here. This genetic marker can be very useful for the accurate identification of these two species in foie gras products. PMID- 22063769 TI - Comparison of six crossbred lamb types: sensory, physical and nutritional meat quality characteristics. AB - The effect of crossbreeding on lamb meat quality was examined on the M. longissimus dorsi and M. semimembranosus of South African lamb breed combinations. The lambs were sired by Dormer (D) and Suffolk (S) rams and born to Merino (M), Dohne Merino (DM) and SA Mutton Merino (SAMM) ewes to give six breed combinations. Ratings of sensory attributes on the M. semimembranosus of the different lamb breed combinations were obtained from a trained descriptive panel. The moisture, total lipids, protein, ash, mineral content and fatty acid composition of the M. semimembranosus were also obtained. Physical parameters measured on the M. longissimus dorsi were: pH(48), drip loss, cooking loss and Warner-Bratzler shear force (WBS). Breed did not have a significant effect (P>0.05) on the sensory quality of lamb, except for D*SAMM lambs which only showed a significantly higher (P?0.05) initial juiciness compared to S*M. However, breed had a significant effect on pH(48), WBS, protein content and the fatty acid and mineral composition. PMID- 22063770 TI - Effect of the relative humidity of drying air during the resting period on the composition and appearance of dry-cured ham surface. AB - This study evaluates the effect of three different relative humidities (RH) during the resting period on the composition of the external part of Semimembranosus muscle (2 mm thick) and the appearance of the surface of the dry cured ham after resting and ageing. Forty-eight hams stored after salting for 40 days at 4+/-1 degrees C and three different RH (52+/-3, 78+/-3 and 85+/-3%) were studied. Half of the hams in each treatment were sampled after the resting period and the rest were aged for 8 additional months at the same temperature and RH. Storage of hams at 52% RH during resting produced a white appearance in some parts of the rind and increased the surface covered with oil drip. Hams stored at 78% showed a similar composition to those stored at 52%, except for the higher moisture content and lower Na/moisture ratio at the end of the resting period, and potassium content (on dry matter, dm) at the end of the process. At the end of resting no white rind was observed, and at the end of the process the surface covered with oil drip was slightly lower than at 52%. Storage of hams at 85% RH increased the surface pH, Na2HPO4.12H2O crystallisation, Mg (dm), Mg/moisture, K (dm) and NPN/NT at the end of the resting period, and increased the pH and Mg (dm), Mg/moisture, Na/moisture, K/moisture, the ash (dm) and ash/moisture contents and decreased the a(w) and the surface covered with oil drip at the end of the process. PMID- 22063771 TI - The significance of cooling rate on water dynamics in porcine muscle from heterozygote carriers and non-carriers of the halothane gene-a low-field NMR relaxation study. AB - The post mortem changes in the chemical/physical state distribution of water were followed in pig muscle (M. longissimus dorsi) from heterozygote (n=12) and non carriers (n=12) of the halothane gene exposed to two different cooling profiles using continuous low-field NMR relaxation measurements. T(2) relaxation data were analyzed using distributed exponential fitting analysis. Independent of genotype post mortem changes were observed in the two water populations characterizing water within the myofibrillar space (T(21)) and the extra-myofibrillar space (T(22)), respectively, as a function of chilling regime. The effect was most pronounced in samples from heterozygote carriers of the halothane gene. The obtained results strongly suggest that improved water-holding capacity of muscles upon fast chilling can be ascribed to a reduced accumulation of extra myofibrillar water in the meat post mortem, and it is hypothesized that differences in the accumulation of extra-myofibrillar water post mortem can be ascribed largely to the time at which disruption of cell membrane integrity takes place. PMID- 22063772 TI - Whey protein concentrates effects on pink color development in a cooked ground turkey breast model system. AB - The ability of whey protein concentrates (WPCs) to reduce pink color in cooked ground turkey was investigated. Ground turkey was formulated with no ligand and nitrite and nicotinamide to induce pinking. Five WPCs with 34 or 80% protein were tested and turkey samples were cooked to 80 and 85 degrees C and stored for 1 and 7 days. Three WPCs reduced a* values in turkey without added nitrite or nicotinamide and one WPC reduced nitrite induced pinking. In nicotinamide-induced pink turkey, two WPCs reduced a* values and two WPCs increased pink color. Nitrosylhemochrome was reduced by two WPCs and nicotinamide hemochrome was reduced by one WPC and increased by two WPCs. Increased cooking temperatures enhanced inhibitory effects or reduced reddening effects of two WPCs. Storage time and protein content had minimal effects on pink color. Whey protein concentrates have the potential to reduce the pink defect in cooked uncured turkey, although the mechanism is unclear. PMID- 22063773 TI - The effect of supplementation with expanded sunflower seed on carcass and meat quality of lambs raised on pasture. AB - The use of conventional concentrates in the supplementation of grass-based fed lambs may induce improvements in growth performance and/or carcass quality but may be disadvantageous in fatty acid profile of tissues, with a negative impact in some nutritional indexes. The objective of this trial was to evaluate the effects on growth performance, carcass and meat quality of using unprotected, unsaturated fat as a supplement for grass-fed based lambs. Twenty-four Merino Branco ram lambs raised on pasture, were supplemented with corn whole grain plus sunflower meal or corn whole grain plus expanded sunflower seed, from 20 to 30 kg live weight. The supplement had no effects on growth performance, carcass quality traits, or meat pH, colour estimates (L(*), a(*), b(*)), water-holding capacity, shear force and sensorial attributes. However, lambs supplemented with expanded sunflower seed showed higher proportions of cis-9, trans-11 octadecadienoic acid and trans-vaccenic acid in intramuscular and subcutaneous fat, showing that the inclusion of unprotected lipids in lambs diet was effective in preventing the reduction of rumenic acid (C18:2 cis-9, trans-11) that occurs when conventional concentrates are used as a supplement. PMID- 22063774 TI - Application of constant current, low voltage electrical stimulation systems to pig carcasses and its effects on pork quality. AB - This study examined the effectiveness of a constant current, low voltage electrical stimulation system on improving pork quality when applied to pigs at 2 min post-exsanguination. A total of 48 female Duroc*Large White/Landrace pigs of 85-90 kg liveweight were randomly allocated immediately prior to slaughter to one of four constant current electrical stimulation treatments: control (no electrical stimulation), 50, 200 and 400 mA. Stimulation was applied to pig carcasses at 2 min post-exsanguination for 30 s. No differences (P>0.05) in WB shear force values, muscle lightness or PSE incidence of pork M. longissimus lumborum (LL) was found due to electrical stimulation treatment. Muscle pH of the LL muscle was lower (P<0.001) in carcasses in the 200 and 400 mA treatments compared to those from carcasses in both the 50 mA and control treatment groups, when measured at the various time points from 40 min to 8 h post-slaughter. Although carcasses stimulated with 200 and 400 mA had higher percentage drip loss (P<0.05) and purge (P<0.001), this was not found to impact WB shear force values, muscle lightness or PSE incidence. PMID- 22063775 TI - Effect of low voltage electrical stimulation of pig carcasses and ageing on sensory attributes of fresh pork. AB - The effect of electrically stimulating pig carcasses and ageing on sensory attributes of pork was evaluated in this study. A total of 48 female pigs [Duroc*Large White/Landrace (A; n=24) and Large White/Landrace (B; n=24)] were randomly allocated immediately prior to slaughter to one of two low voltage stimulation treatments; no stimulation or 150 mA applied for 30 s at 2 min post exsanguination. Each side of the carcass was then randomly allocated to an ageing treatment of either 2 or 7 days post-slaughter. Muscle pH of the M. longissimus lumborum was lower (P<0.001) in electrically stimulated carcasses when measured from 40 min to 8 h post-slaughter compared with non-stimulated carcasses. Percentage drip loss, muscle lightness and PSE incidence were not influenced (P>0.05) by electrical stimulation. Electrical stimulation of pig carcasses and ageing pork for 7 days post-slaughter both improved (P<0.001) consumer scores for tenderness, juiciness, overall liking and quality category, however the interaction term of electrical stimulation and ageing was not significant for any of the sensory attributes. Pork from non-stimulated carcasses that was aged for 2 day post-slaughter was less tender (P<0.01) compared with pork in all other treatments. These results indicate that electrical stimulation (150 mA applied for 30 sec at 2 min post-exsanguination) was effective in improving eating quality attributes of pork, particularly when pork was aged for only 2 days post slaughter, without detrimentally affecting colour or drip loss. PMID- 22063776 TI - Effect of stun duration and current level applied during head to back and head only electrical stunning of pigs on pork quality compared with pigs stunned with CO(2). AB - The effect of current, duration and method of application of manual electrical stunning on pork carcass and meat quality attributes in comparison with stunning pigs with CO(2) was investigated. Two experiments were conducted using a total of 96 Large White*Landrace boars (homozygous dominant for the halothane gene). In Experiment 1, 48 pigs were allocated to one of six stunning treatments: CO(2) (90% in air), electrical stunning (ES) using head only (HO) tongs delivering current at a frequency of 50 Hz at 1.3 or 2.0 A for 4 s and 0.9, 1.3 or 2.0 A for 19 s. Higher drip loss occurred in M. longissimus thoracis et lumborum (LTL) muscles from ES pigs, except those stunned with 0.9 A for 19 s, compared with pigs stunned with CO(2). The incidence of pale, soft exudative (PSE) meat was higher in ES pigs, except those stunned at 1.3 A for 4 s, compared with CO(2) stunned pigs. In Experiment 2, 48 pigs were allocated to one of six stunning treatments: ES using a head to back (HB) handpiece delivering current at 1.3 or 2.0 A for 4 s and 0.9 or 1.3 A for 10 s; HO 1.3 A for 4 s or CO(2). Although stunning treatment did not influence ultimate pH, muscle lightness, tenderness or cooking loss, drip loss and PSE incidence in LTL muscles from CO(2) stunned pigs were lower compared with ES pigs. Overall, ecchymosis and bone fractures were more prevalent in ES pigs compared with CO(2) stunned pigs. This research identified that stunning pigs with CO(2) compared with manual ES lowered the incidence of bone fractures, ecchymosis, PSE and drip loss of pork. PMID- 22063777 TI - Effect of transport time and ageing on aspects of beef quality. AB - Forty-eight bulls were transported by road in groups of eight for approximately 30 min, 3 or 6 h in two replicates. After slaughter, steaks from the longissimus dorsi thoracis of all transported animals were analysed in terms of pH, water holding capacity, myoglobin concentration, texture at 7 and 14 days of ageing (compression and Warner-Bratzler analyses) and colour of the same surface of meat cut at 24 h post-mortem and allowed to bloom for 24 h and 7 d (L(*)a(*)b(*), chroma and hue). The myofibrillar resistance of the meat from animals transported 30 min was significantly greater at 20% compression (P<0.05). The maximum load and a(*)b(*) and chroma were all lower for meat aged 14 days. PMID- 22063778 TI - The influence of RN genotype, including the new V199I allele, on the eating quality of pork loin. AB - The eating quality of M. longissimus dorsi (LD) from RN(-) homozygotes, RN(-) heterozygotes and RN(-) non-carriers was investigated in a Swedish Hampshire*Finnish Landrace pig population. The recently identified new allele (V199I, here denoted rn*) at the RN locus was also detected among the pigs selected and included in the sensory evaluation. The number of animals varied from 10 to 15 in the five genotype groups; RN(-)/RN(-), RN(-)/rn+, RN(-)/rn*, rn+/rn+ and rn+/rn* (in total 59 pigs). In addition, one pig was determined to be rn*/rn* but was excluded from the analysis. The three genotypes in which the RN( ) allele was represented (RN(-)/RN(-), RN(-)/rn+ and RN(-)/rn*) had higher glycogen and lower protein contents as well as lower ultimate pH (measured 48 h post-mortem) in LD than the non-carriers (rn+/rn+ and rn+rn*). Of the sensory parameters evaluated (tenderness, chewing time, chewing residual, juiciness, meat flavour and acidity), the five RN genotypes only affected acidity significantly; the RN(-) allele contributing to a more acid taste in LD. The influence of the rn* allele resembled that of rn+ on the sensory parameters. When the material was divided into three groups (homozygous, heterozygous and non-carriers of the RN(-) allele) the juiciness was found to be significantly influenced by RN genotype, and LD from animals that were homozygous and heterozygous with respect to the RN( ) allele exhibited a higher juiciness than LD from non-carriers. The RN(-) allele also tended to contribute to greater tenderness, which was significantly higher in LD from heterozygous carriers than from non-carriers of the RN(-) allele. A more rapid decline in pH (measured as pH at 45 min and 3 h post-mortem) contributed to a greater tenderness in LD (according to a trained panel and Warner-Bratzler shear force). In addition to the RN genotype, the decline in pH was influenced by carcass weight, which varied between 71 and 97 kg, and by stunning procedure, which changed during the course of the study from individual to group stunning with CO(2). The individual stunning procedure contributed to a lower pH in the initial post-mortem phase (pH(45)), whereas a higher carcass weight and the RN(-) allele lowered the pH in the mid-post-mortem region (pH(3h) and pH(24h)), significantly (P?0.05). The pH continued to decline after 24 h post mortem and the ultimate pH was not reached until 48 h post-mortem. The cooking loss, juiciness and acidity were related to the specific characteristics of the RN(-) carriers, such as higher glycogen content, lower protein content and lower ultimate pH (pH(48h)). PMID- 22063779 TI - Effect of phosphate with tumbling on lipid oxidation of precooked roast beef. AB - This study was a 4*2*4 factorial experiment, sodium tripolyphosphate (0, 0.25, 0.4 and 0.5%), tumbling (nontumbled and tumbled), and storage time (day 0, 2, 4 and 7). Cooking yield was dependent on the level of phosphate and tumbling. For thiobarbituric acid reactive substances (TBARS) values, only sodium tripolyphosphate level and storage time had a significant two-way interaction. The TBARS value of tumbled roast beef with phosphates was the same as that of nontumbled roast beef. For the interaction of phosphate level and storage time, roast beef without phosphate had the significantly highest TBARS values compared with other phosphate levels at day 4 of storage. At day 7, the addition of 0.5% phosphate maintained the oxidative stability of precooked roast beef. The use of 0.5% sodium tripolyphosphate, an iron chelator, should be an effective strategy to reduce the formation of TBARS in precooked roast beef. PMID- 22063780 TI - Improvement of nutritional properties of Chorizo de Pamplona by replacement of pork backfat with soy oil. AB - Dry fermented sausages with a partial substitution of 15, 20 and 25% of pork backfat by pre-emulsified soy oil were prepared. No differences were detected in the water, protein and fat content between control and modified sausages. Cholesterol amount scarcely decreased in the modified sausages (92.96 mg/100 g product in control sausages, 87.71 mg/100 g in sausages prepared with 25% of substitution). No increase in oxidation was detected through chemical or sensory analysis in modified sausages. Saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) in control products were 37.83 and 45.78 g/100 g of total fatty acid, respectively, decreasing in the modified formulations, to 32.81 and 42.09 g/100 g of total fatty acid in the 25% replacement products, respectively. Polyunsaturated fatty acids (PUFA) increased from 15.22 (control) to 23.96 g/100 g of total fatty acid (25% product) due to the significant increase in linoleic and alpha-linolenic acids when soy oil was added. In relation to texture profile analysis (TPA), hardness and springiness did not show significant differences among products. The instrumental measured colours were comparable with that of commercial products. Sensory evaluation of most of the modified sausages did not show significant differences with regard to the control. PMID- 22063781 TI - Effect of sex and terminal sire genotype on performance, carcass characteristics, and meat quality of pigs slaughtered at 117 kg body weight. AB - The effects of gender (barrows; gilts) and terminal sire genotype (DD, Danish Duroc; PxLW, Pietrain*Large White) on performance and carcass and meat quality of pigs sacrificed at a fixed weight of 117 kg were studied. Barrows ate more feed, grew faster, and had poorer feed conversion and less yield of trimmed lean cuts than gilts. Castrates were fatter and had more intramuscular fat and more intense colour of the meat than females. Crossbreds from DD boars grew faster and had better feed conversion than crossbred from P*LW boars. Also, DD sired-pigs had smaller dressing percentages but more trimmed lean cuts proportion than P*LW sired-pigs. Meat from DD pigs was more tender, had more intramuscular fat, and presented lower a* value than meat from P*LW pigs. We conclude that DD boars are a good alternative to P*LW boars for production of heavy pigs destined for the dry-cured industry. PMID- 22063782 TI - Effect of dietary energy content on the intramuscular fat depots and triglyceride composition of river buffalo meat. AB - The production of river buffalo meat in Italy has long been under discussion due to poor acceptance by consumers. In order to understand whether dietary energy content may affect the organoleptic characteristics of buffalo meat, two groups of river buffalo calves were fed on two diets, with high (H) and low (L) energy contents. The animals were slaughtered at 4-monthly intervals starting from 6 months old (10, 14 and 18 months) and five muscles were dissected on the half carcass: Caput longum tricipitis brachii (CloTB), Gluteobiceps (Gb), Semitendinosus (St), Semimembranosus (Sm) and Longissimus dorsi (LD). The results showed that from 6 to 10 months of age the meat lipid content decreases and protein content increases for both diets. The lipid content increases slowly with both diets from 10 to 14 months. In the last experimental period (from 14 to 18 months) an increase in the percentage of lipids with diet H and a decrease with diet L was observed. At all slaughtering ages the meat from the animals fed on diet H had a higher energy content. The different energy content of the two diets did not significantly influence the composition of triglycerides only formed by SFA and triglycerides with a higher degree of unsaturation. The triglycerides with an unsaturated fatty acid in position sn 2 did not show the same behaviour in relation to age and diet. The energy content of the feed did influence the unsaturated fatty acid composition: MUFA increased with an increased energy level of the diet, while PUFA increased with a reduction in the energy level of the diet. The muscle LD showed a significantly higher (P<0.05) content of SFA and lower (P<0.05) of MUFA and PUFA than the other muscles. On the basis of our results, the better TAG's composition is found in the meat of animals fed on diet H and slaughtered at 4 months of age. PMID- 22063783 TI - Physicochemical and sensory characteristics of restructured beef steak with added walnuts. AB - The effects of different proportions (0, 5, 10, 15%) of added walnuts on the physicochemical and sensory characteristics of restructured beef steak were evaluated. The addition of 10 and 15% walnut reduced (P<0.05) cooking loss. Increasing proportions of walnut in the beef steak increased (P<0.05) water binding and reduced (P<0.05) fat binding properties. The addition of walnut did not affect (P>0.05) textural properties in uncooked restructured beef steak, but in cooked products Kramer shear force and bind strength were reduced (P<0.05) when 10% or more of walnut was added. Product morphology characteristics suggest that walnut interferes with the formation of protein network structures. Restructured steaks made with added walnut presented acceptable sensory properties. Incorporation of nuts in meat products can be use to confer potential heart-healthy benefits (Spanish Patent Application 200300367). PMID- 22063784 TI - Mathematical relationships between the intake of n-6 and n-3 polyunsaturated fatty acids and their contents in adipose tissue of growing pigs. AB - To establish the relationships between the fatty acid composition of adipose tissue in growing pigs and the intake of fatty acids, we performed a feeding trial and did a literature survey. Six groups of pigs were fed diets with variable combinations of corn, linseed and fish oil. After 38 days, biopsies of adipose tissue were analyzed for their contents of linoleic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acid. For the four fatty acids, intake data and adipose tissue levels were also collected from the literature. Linear correlations were computed for the intake of each polyunsaturated fatty acid and its level in adipose tissue, the data set consisting of either the original results only or combined with literature figures. The observed strong correlations between dietary and fat tissue polyunsaturated fatty acids indicate that the fatty acid composition of the diet may be used as an index of the fatty acid composition of the diet, and vice versa. The regression equations presented can be used to steer the fatty acid composition of adipose tissue of growing pigs by the fatty acid composition of their diet. PMID- 22063785 TI - True retention of nutrients on cooking of Australian retail lamb cuts of differing carcass classification characteristics. AB - The true retention of nutrients (proximate principles and cholesterol) on cooking of three retail cuts from lambs classified by weight, sex and fatness score was investigated. Fat retentions of the total cut and of the lean portion of lamb legs and mid-loin chops were not affected by carcass fatness, weight and sex or their interactions, however, the fat retention of the total cut and of the lean portion of forequarter chops was affected by fat score, with forequarter chops from fat score 1 retaining more fat than did chops of carcasses of higher fat score. Overall, fat was lost by all cuts (total cut) on cooking, with only 70-80% of fat being retained, but fat content of lean only increased on cooking (retention >100%), indicating the passage of fat into the lean portion from the external fat cover during the cooking process. Carcass factors and their interactions had little or no effect on the protein, water and ash retentions of the total cut or the lean portions of the three cuts. Cholesterol retention by the lean portion of three cooked lamb cuts was not affected by any carcass factors or their interactions. Cholesterol retentions were ~99% for total cuts and tended to be ~102% for the lean portions. PMID- 22063786 TI - Lipid composition of Australian retail lamb cuts with differing carcass classification characteristics. AB - The gross, proximate, fatty acids and cholesterol composition of three raw retail cuts from 28 lambs classified by weight, sex and fatness score were investigated. For gross composition, cut weight increased significantly with fat score and carcass weight. Percentage fat increased significantly from fat score 1-2 but not beyond (P<0.05). For nutrient composition the fat contents of the total cut and lean only portion of the three cuts increased directly with fat score by 10 g/100 g and 1.7 g/100 g, respectively. Fat content increased mainly at the expense of moisture. Cholesterol content of total cut and lean only portions decreased with increased fat score, by 16 and 18 mg/100 g, respectively. For lean only levels of myristic and palmitic acids increased significantly (P<0.05) while stearic acid decreased significantly, while levels of linoleic and linolenic acids decreased significantly with increased fat score. PMID- 22063787 TI - Detection of factors influencing nitrite determination in meat. AB - A critical assessment was made of the official Spanish method for determining nitrite content in meat, using a 2((k-p)) fold-over Plackett-Burman experiment to identify influencing factors (IF) affecting the analytical method; these factors were drawn from seven apparent critical factors (ACF): sample weight (W(S)), extraction temperature (T(E)), stirring extraction time (S(ET)), addition of Carrez I reagent (C(I-R)), addition of Carrez II reagent (C(II-R)), addition of borax reagent (B(R)) and color development time (D(CT)). In the experimental conditions assayed, the analytical method does not require protein precipitation. In addition, a negative effect of the Carrez reagent on nitrite determination was detected; it is thus proposed that this reagent be eliminated, in accordance with AOAC method 973.31. The use of borate improved nitrite extraction, but the W(S)/B(R) ratio must be adjusted to determine the best ratio and to eliminate any negative effect when the ratio increases. PMID- 22063788 TI - P(y)-a parameter for meat quality. AB - The P(y) is a parameter which assesses the integrity of the cell membranes. It is a direct indicator for the volume fraction of cells surrounded by insulating cell membranes. The P(y) has been shown to correlate well with meat quality parameters like the drip loss or pH. It is a useful parameter for the discrimination between normal suited meat and PSE meat. The measurement is instantaneous and nondestructive. Due to aging of meat, P(y) depends on the time post mortem. It shows the highest significance between 4 and 24 h p.m. PMID- 22063789 TI - Changes in meat quality characteristics of bovine meat during the first 6 days post mortem. AB - The development of some quality parameters in bovine meat during the first 6 days of post mortem ageing was studied in two commercial groups (heifer and bull). In the first day bull meat is harder and springier. Meat pH falls during the first 24 h post mortem in both groups, reaching values around 5.5, and it did not change during the next 5 days. Water-holding capacity (expressed as percentage of expelled water) increased in heifer meat. Instrumental texture measures (texture profile analysis, TPA) showed a decrease in hardness, springiness and chewiness in bull raw meat. Sensory analysis showed that assessors perceived a decrease in hardness and in springiness in bull meat and a decrease in juiciness and in chewiness (number of chewings before swallowing) in heifer meat. Ageing showed no effect on assessors' pleasantness either in heifers' or in bulls' meat. During the first 3 days, heifer meat was juicier. Heifers' meat produced a greater pleasantness on the sixth day. Both meats were not very different for most quality parameters studied in this work. PMID- 22063790 TI - Impact of Helicobacter pylori infection on severity of psoriasis and response to treatment. AB - The aims of this study were to determine the prevalence of H. pylori seropositivity in patients with psoriasis, to evaluate the relationship between PASI (Psoriasis Area and Severity Index) scores and H. pylori infection, and to assess the impact of H. pylori infection on the response to treatment. A total of 300 patients with psoriasis and 150 non-psoriatic healthy controls were enrolled in the study. Patient PASI scores were recorded and H. pylori stool antigen tests performed in both patients and controls. Fifty patients with H. pylori infections were randomly assigned to one of two groups, one of which received acitretin with H. pylori treatment and the other acitretin alone. Statistical analyses were performed using chi-square and logistic regression tests. PASI scores were significantly higher in patients with H. pylori infections. Treatment aimed at eradicating H. pylori infection enhanced the effectiveness of acitretin therapy and shortened response times. Our results suggest that H. pylori infection plays a role in the severity of psoriasis, and that eradicating such infections enhances the effectiveness of psoriasis treatment. PMID- 22063791 TI - Investigation of the physicochemical and sensory homogeneity of traditional French dry sausages. AB - The aim of this study was to investigate the homogeneity of the traditional dry sausages manufactured in small scale facilities from the Massif Central region in France by taking into account the diversity of the production in this area. The homogeneity was estimated by analysis of the physicochemical parameters of 6 types of traditional dry sausages chosen as representatives of the production diversity. The homogeneity was evaluated (i) within the product, (ii) in the production batch and (iii) over 2 different seasons for each type of dry sausage. When heterogeneity was detected, sensory analysis was performed in order to check if the physicochemical differences found were perceived by a sensory panel. The physicochemical results showed that there was no significant heterogeneity within the product nor there was in the production batch. Over the 2 seasons studied, 3 out of the 6 dry sausages were heterogeneous in composition and this feature was perceived by the sensory panel. The possible causes of this heterogeneity (amounts of ingredients added, type and composition of the raw materials used, length of drying) are discussed. PMID- 22063792 TI - The effects of shelf-life enhancers on E. coli K12 survival in needle-injected, surface contaminated beef strip steaks enhanced using recycled solutions. AB - The objective of this study was to evaluate the efficacy of shelf-life enhancers (sodium lactate [SL] or sodium lactate + sodium diacetate [SLDA]) on limiting the growth of Escherichia coli K12 in needle-injecting surface-contaminated beef strip steaks with recycled enhancement solutions. Strip loins were injected to 10% over initial weight. SLDA was most effective in controlling bacterial growth followed by SL alone. The salt/phosphate combination in the enhancement solution was ineffective. SL decreased a(*) (less red) and b(*) values (less yellow) of the steaks compared to the salt/phosphate control. SLDA decreased L(*) values compared to SL alone. SL and SLDA were equally effective in reducing purge loss from the steaks. Steaks enhanced with a "fresh" enhancement solution had higher a(*) values (more red) and higher E. coli contamination levels than steaks enhanced with recycled solutions. Recycling did not affect L(*) value, b(*) value, or purge loss. PMID- 22063793 TI - A survey of pork quality in relation to pre-slaughter conditions, slaughterhouse facilities, and quality assurance. AB - A survey at five pigs' slaughterhouses was performed to investigate the effect of a quality assurance system, pre-slaughter conditions and slaughterhouse facilities on pork quality. Totally, 2246 pigs were included over four transports per slaughterhouse, i.e. two transports were produced according to a quality assurance system and the other two were conventional pigs. Meat quality was measured on 446 pigs. The pH in the longissimus dorsi muscle and the electrical conductivity in the semimembranosus muscle were measured 30min post-mortem. Twenty-four hours later pH and electrical conductivity in both the longissimus dorsi and the semimembranosus muscle were measured. Pigs managed according to a chain quality protocol showed an overall higher potential for improved meat quality. Differences in meat quality between the different slaughterhouses were also found, however they were dependent on muscle type and time of measuring. Influencing factors on pork quality seemed to be stocking density during transport, the handling during offloading the pigs from the truck, stocking density, and air temperature during lairage. PMID- 22063794 TI - Carcass composition and meat quality of three different Iberian*Duroc genotype pigs. AB - Carcass composition and meat quality of Longissimus dorsi (LD) and Biceps femoris (BF) muscles from three different Iberian*Duroc genotype pigs were studied: GEN1: ? Iberian*? Duroc1; GEN2: ? Duroc1*? Iberian; GEN3: ? Duroc2*? Iberian. Duroc1 (DU1) were selected for the manufacture of dry-cured meat products while Duroc2 (DU2) were pigs selected for meat production, with high percentages of meat cuts and low carcass fat. Genotype had a significant effect on the differences found while sex had not. GEN2 showed the highest weights at days 180 and 238 of weaning and the highest slaughter weights (day 316) followed by GEN3, while the lowest weights were found in GEN1. GEN3 had well conformed carcasses in comparison with GEN1 and GEN2, since GEN3 showed the highest percentages of ham and loin and the highest weight of loin as well as the lowest back and ham fat thickness. However, the use of DU2 pigs in the cross with Iberian had negative effects on meat quality, as GEN3 gave the worst meat quality in both muscles, postmortem pH, cook and drip loss, and colour and the lowest percentages of intramuscular fat (IMF). In subcutaneous fat (SCF), GEN3 had higher percentages of polyunsaturated fatty acids (PUFA) than GEN2, while GEN2 had higher saturated fatty acids (SFA) levels. In LD, IMF from GEN3 showed the highest percentage of MUFA and PUFA; while the fatty acid profile of GEN2 was more saturated. BF muscle showed similar trends, but not significantly so. On the other hand, few differences were found between reciprocal crosses (GEN1 vs. GEN2). GEN2 showed higher IMF in LD than GEN1, agreeing with their carcass weight. As a result, GEN1 had a fatty acid profile of IMF in the LD that was more unsaturated. PMID- 22063795 TI - Biogenic amines in pressurized vacuum-packaged cooked sliced ham under different chilled storage conditions. AB - This work was undertaken to study how storage conditions (at constant temperatures of 2+/-1 and 12+/-1 degrees C and temperature fluctuations at 7+/-5 degrees C) affect microbial development and the production of biogenic amines in vacuum-packaged cooked sliced ham subjected to high pressure (400MPa/10min/30 degrees C). Initially, the product exhibited low levels of contamination. Microbiological changes during storage depend on the processing (non-pressure and pressure treatment) and the chilled storage conditions. Generally, microbial growth in pressurized samples was similar to that in the non-pressurized samples, although the total viable count and lactic flora were lower and growth was delayed. Processing and storage conditions affected the formation of each amine differently. The most important changes were in tyramine, which formed more quickly in non-pressurized products stored at 12 degrees C and with temperature fluctuations. The formation of biogenic amines in these products can be prevented not only by ensuring good manufacturing practices and applying high pressure but also by ensuring the right chilled storage conditions. PMID- 22063796 TI - Ion distribution and protein proteolysis affect water holding capacity of Longissimus thoracis et lumborum in meat of lamb subjected to antemortem exercise. AB - Exercise has been shown previously to reduce the water holding capacity (WHC) of meat in lamb. The consequence of changes in the distribution of ions pre- and post-rigor and proteolysis on WHC is relatively unknown. Twelve crossbred lambs were used to investigate the effect of exercise on the meat quality traits of the Longissimus thoracis et lumborum (LTL) muscle. There were no treatment effects on Warner-Bratzler shear force (WBSF), myofibril and sarcoplasmic protein solubility, denaturation or sarcomere length. With exercise the initial pH of the muscle was lower and the rate of pH fall to rigor was faster compared to controls. Exercise caused increased purge and meat fluid had a lower osmolarity, magnesium, potassium and sodium concentration. Proteolysis of desmin occurred after day 3 and vinculin on day 7 of ageing with exercise. It was concluded that exercise caused changes in the distribution of ions and the proteolysis of muscle proteins that reduced the ability of the muscle to bind or hold water. PMID- 22063797 TI - Variability in temperature distribution and cooking properties of ground pork patties containing different fat level and with/without salt cooked by microwave energy. AB - This study was carried out to evaluate the cooking effects of fat level (10% and 20%) with and without NaCl (1.5%) on the microwave cooking pattern and properties of ground pork patties. Each patty was cooked from a thawed state to 76.7 degrees C in a microwave oven with full power (900W). Cooking rate in patties produced without salt was not affected by fat level, but the addition of salt in pork patties decreased cooking rate, regardless of fat levels. The temperatures at the edges of the patties increased faster than those at the center or the mid-way positions. In the patties with NaCl, the temperature of the center position was higher than that of the mid-way position. Patties containing salt within the same fat level had higher moisture content and lower fat content than those without salt, although no significant differences in compositional properties were observed between the center, midway, or edge positions. Total cooking loss, drip loss, and reduction in diameter and thickness were higher in patties with 20% fat compared to those with 10% fat, but the addition of salt resulted in reduction, regardless of fat level. Also, the addition of salt increased the redness and reduced yellowness of the cooked products. PMID- 22063798 TI - Effect of low dose gamma irradiation on beef quality and fatty acid composition of beef intramuscular lipid. AB - Eight Chinese Yellow Cattle semitendinous muscles were irradiated using a (60)Co irradiation source (with the dose of 1.13, 2.09, or 3.17kGy) and stored (0 day or 10 days at 7 degrees C) to estimate fatty acids change of neutral lipid (NL), polar lipid (PL) and total lipid (TL) fractions, and the beef quality change. Total saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) increased with irradiation, ratios of MUFA to SFA did not change in TL. Whilst, total polyunsaturated fatty acid (PUFA) reduced with irradiation, which resulted in PUFA to SFA ratio decreased in TL (0 day or 10 days). Purge loss and 2 thiobarbituric acid reactive substances values increased with irradiation (from 0 to 3.17kGy) at 0 day, but these values were lower with irradiation at 10 days. Total bacterial counts decreased proportionally with irradiation dose increasing from 0 to 3.17kGy. It can be concluded that fatty acid profiles in beef changed with irradiation; however, fatty acid profiles did not change much at 3.17kGy compared with 1.13 or 2.09kGy, and the beef quality were most acceptable at the dose of 3.17kGy, thus, low dose of about 3kGy gamma irradiation was recommended to apply in fresh beef preparation. PMID- 22063799 TI - Influence of carbon monoxide in package atmospheres containing oxygen on colour, reducing activity, and oxygen consumption of five bovine muscles. AB - Steaks from five bovine muscles [psoas major (PM), longissimus lumborum (LL), deep semimembranosus (DSM), superficial semimembranosus (SSM), and semitendinosus (ST)] were packaged in atmospheres containing 20% or 80% oxygen, with and without 0.4% carbon monoxide. Steaks were evaluated on d 0, 4, and 7 of retail display for instrumental (CIE L(*), a(*), and b(*)) and visual colour, total- and metmyoglobin-reducing activity, and oxygen consumption rate. Combining carbon monoxide with either oxygen level had no effect (P>0.05) on any measured attribute. Using higher oxygen levels increased colour stability and reduced variability (P<0.05) among muscles for all measured attributes. In general, colour stability and reducing activity for the muscles were LL>ST>SSM>PM>DSM. Including 0.4% carbon monoxide with 20% or 80% oxygen may not have impacted colour, due to preferential formation of oxymyoglobin, rather than carboxymyoglobin, at these oxygen levels. PMID- 22063800 TI - Effect of illumination on the display life of fresh pork sausages packaged in modified atmosphere. Influence of the addition of rosemary, ascorbic acid and black pepper. AB - Pork forelegs were used for manufacturing fresh sausages, treated with different natural antioxidants (rosemary, ascorbic acid and black pepper), packaged in 80% O(2)+20% CO(2) atmosphere and displayed at 2+/-1 degrees C under different lightings (darkness, standard fluorescent, low-UV colour-balanced lamp and standard fluorescent plus a UV-filter). Two packs for each treatment were opened every 4 days for subsequent analysis of colour CIE L(*), a(*), b(*), TBARS, microbial psychrotrophic aerobes and sensory discolouration and off-odour. Lighting with standard fluorescent was highly deleterious for sausage display life, which fell from 12 to 8 days due mainly to early discolouration. Inserting a UV-filter extended display life to 12 days, while the use of a low-UV lamp was not effective in protecting from discolouration. Addition of rosemary plus ascorbic acid, in the absence of black pepper, retarded discolouration only in sausages illuminated with the UV-filter, reaching a display life of 16 days, equal to that of sausages maintained in the dark. PMID- 22063801 TI - Effect of different binders on the quality of enrobed buffalo meat cutlets and their shelf life at refrigeration storage (4+/-1 degrees C). AB - To enhance the binding and quality of enrobed buffalo meat cutlets (EBMC), a meat emulsion at 0%, 15%, 20% and 25% replaced the cooked meat in the formulation. Emulsion containing products had significantly higher moisture contents and texture scores compared to the control. Emulsion at 20% level could be incorporated in enrobed buffalo meat cutlets to enhance their quality. Addition of 1% egg white powder improved the quality of EBMC compared to control, while a 3% level had adverse effect on the sensory attributes despite giving higher product yield and lower shrinkage. Cutlets with refined wheat flour had significantly higher protein and fat contents. It had also higher acceptability followed by corn flour, potato starch and tapioca flour. TBARS of enrobed samples remained lower than controls throughout the storage period. Mesophilic count remained below log3cfu/g for both samples during storage. Uncoated products and enrobed products were acceptable up to 10th and 15th day, respectively. Enrobing of buffalo meat cutlets improved their acceptability and shelf life under refrigeration storage. PMID- 22063802 TI - Aminogenesis control in fermented sausages manufactured with pressurized meat batter and starter culture. AB - The application of high hydrostatic pressure (200MPa) to meat batter just before sausage fermentation and the inoculation of starter culture were studied to improve the safety and quality of traditional Spanish fermented sausages (fuet and chorizo). Higher amounts of biogenic amines were formed in chorizo than in fuet. Without interfering with the ripening performance in terms of acidification, drying and proteolysis, hydrostatic pressure prevented enterobacteria growth but did not affect Gram-positive bacteria significantly. Subsequently, a strong inhibition of diamine (putrescine and cadaverine) accumulation was observed, but that of tyramine was not affected. The inoculated decarboxylase-negative strains, selected from indigenous bacteria of traditional sausages, were resistant to the HHP treatment, being able to lead the fermentation process, prevent enterococci development and significantly reduce enterobacteria counts. In sausages manufactured with either non-pressurized or pressurized meat batter, starter culture was the most protective measure against the accumulation of tyramine and both diamines. PMID- 22063803 TI - An examination of factors affecting radio frequency heating of an encased meat emulsion. AB - The potential of radiofrequency (RF) heating for rapid cooking of a cased comminuted meat emulsion (white pudding) to a pasteurisation temperature of 73 degrees C was examined. Immersion of the product in water was essential in order to prevent thermal damage to the casings by electrical arcing effects during heating. Using a polyethylene heating cell with non-circulating water the applied RF power, primary electrode distance as well as the mineral content, temperature and volume of the surrounding water all influenced the efficiency of the RF heating. Under optimised conditions maximum/minimum temperature gradients (DeltaT) across the products in excess of 15 degrees C were observed. These could be reduced to around 6 degrees C by heating the white puddings in a cell operating with recirculating hot water (80 degrees C). Using an oven power output of 450W a 4.3-fold reduction in cooking time compared to conventional steam oven cooking could be achieved. PMID- 22063804 TI - Effect of thawing rate on distribution of an injected salt and phosphate brine in beef. AB - Striping or streaking is a problem in moisture enhanced meats which are injected to low levels. Research was undertaken to determine brine distribution paths and effect of pre-injection thawing rate on brine distribution. Beef rib eyes and eye of rounds were vacuum packed and aged 7 days at 3 degrees C, then frozen (-35 degrees C) for a month, thawed either quickly in water (5h at 12-17 degrees C) or slowly in air (48h at 3 degrees C), injected to 108-110% using a conventional brine containing blue food colouring, chilled overnight, then cut along four planes and photographed for image analysis of % blue, % marbling, and subjective evaluation of brine distribution paths. There were no significant differences in % blue due to treatment. Brine distribution in both muscles was better parallel to fibers than perpendicular to them. A subset of aged rib eyes was injected to 125%. Although brine was more extensively distributed than at lower injection levels, basic patterns remained unchanged. PMID- 22063805 TI - Mineral content of longissimus dorsi thoracis from water buffalo and Zebu influenced cattle at four comparative ages. AB - The longissimus dorsi thoracis (LDT) of 64 water buffalo and 68 Zebu-influenced cattle was used to determine the mineral content variation (mg/100g of fresh tissue) according to species, age (7, 17, 19 and 24 months-of-age, MOA) and gender (steers and bulls). Buffalo LDT had higher concentrations of K, Mn, Fe, Zn and Cu at weaning (P<0.05). Phosphorous content was higher (P<0.05) at post weaning ages. Mineral profile was affected by age without clear trends; the Na and K contents increased at 24 MOA. The age*species, age*gender and species*gender interactions affected (P<0.05) Fe content that ranged from 1.74 to 2.56mg/100g fresh tissue. Meat from both species contributes with more of 25% of K, P, Fe and Zn of the daily requirement for an adult. PMID- 22063806 TI - Comparison between rabbit lines for sensory meat quality. AB - Rabbits from three synthetic lines were used in the experiment. Line R was selected for growth for 24 generations. Lines V and A were selected for litter size at weaning for 30 and 33 generations, respectively. Sensory analysis was carried out on the Longissimus muscle. The parameters evaluated were: juiciness (J), hardness (H), fibrousness (F), flouriness (Fl), intensity of rabbit flavour (IRF), aniseed odour (AO), aniseed flavour (AF), liver odour (LO) and liver flavour (LF). A Bayesian analysis was performed. Line V was only 82% as juicy as line R. Line V was 18% harder and 17% more fibrous than line R. Lines A and R had the same H and F. No differences in Fl were found. Small effects were found for flavour traits. We conclude that line origin has an influence on some sensory traits determining rabbit meat tenderness. PMID- 22063807 TI - Difference in tenderness and pH decline between water buffalo meat and beef during postmortem aging. AB - The objective of this research was to determine the difference in tenderness and some characteristics of water buffalo meat and beef during postmortem aging. Five female crossbred water-buffalo (Philippine Carabao*Bulgarian Murrah) and five female crossbred cattle (Brahman*Philippine Native), were finished on the same diet for 6 months and slaughtered at 30 months of age. The muscle pH was measured at 40min, 3h, 7h, 24h, and 48h postmortem. Longissimus thoracis (LT) and semimembranosus (SM) muscles were excised at 2d postmortem, and shear force was measured at 2, 4, 7, and 14d postmortem. Glycogen and lactate concentrations were determined from 0, 2, and 4d LT samples, and myosin heavy chain type of buffalo and cattle LT was determined by ELISA methods. Myofibrillar protein degradation was also observed by SDS-PAGE and Western blotting of fast-type troponin T. Results showed that the buffalo meat had significantly lower shear force values compared to beef for LT and SM muscles, which was supported by a difference in troponin T degradation. Postmortem pH decline of buffalo meat was significantly slower than that of beef, which was confirmed by lactic acid concentrations, but was not explained by glycogen content. In addition, there was no significant difference in the ratio of slow to fast type muscle fibers in buffalo and cattle, indicating that myosin heavy chain type was not responsible for the difference in pH decline and tenderness between the buffalo meat and beef. This study demonstrated that the tenderness of water buffalo meat was superior to that of Brahman beef, which may have been due to the difference in pH decline and the subsequent effect on muscle protease activity. PMID- 22063808 TI - Postmortem changes in bovine troponin T isoforms on two-dimensional electrophoretic gel analyzed using mass spectrometry and western blotting: The limited fragmentation into basic polypeptides. AB - To comprehend postmortem changes in troponin T (TnT), whole beef proteins were developed on a two-dimensional electrophoretic gel. Multiple TnT-related spots were identified by both western blotting and MALDI-TOF MS utilizing bovine TnT isoform mRNA sequences. More than 10 TnT fast-type isoform spots (pI 5.7-9.6<) and the two slow-type isoform spots (pI 5.6-5.7) were observed at slaughter. All the isoforms were degraded exclusively into basic spots (pI 9.6<) at day 14 postmortem. Some TnT-related phosphorylated spots present at slaughter had disappeared by day 14, suggesting that the phosphorylated N-terminal region was cut off during beef aging. The intact isoforms and the fragments were identified by the MS with sequence coverage of 20.8-62.7%, and two of the fragments included the cutting site peptide of a conventional 30kDa or of a slow TnT-derived fragment. These results revealed that all of the TnT isoforms are cut exclusively in the glutamic acid-rich amino-terminal region during postmortem aging. PMID- 22063809 TI - Effect of modified atmosphere packaging on the microbiological and sensory quality on a dry cured beef product: "Cecina de leon". AB - The aim of this study was to investigate the shelf-life of commercial "Cecina de Leon" (CL) packaged in vacuum (VP) and in CO(2)/N(2) atmospheres (20/80% CO(2)/N(2) and 80/20% CO(2)/N(2)). Packaged product was stored at 6 degrees C, measuring microbiological, physico-chemical and sensory parameters during 210 days. The values obtained for mesophilic aerobic, anaerobic and psychrotrophic counts did not vary in both the vacuum and the gas packaged samples after 210 days of storage. Enterobacteria and enterococci were always below the detection limit, and in the gas-packaged CL, pseudomonad numbers were significantly inhibited. No changes were observed in the counts of the typical microflora of CL (Lactic Acid Bacteria, yeasts and moulds and Micrococcaceae) up to 210 days and no differences (p>0.05) were found between the counts in the VP and in the gas packaged samples. A pronounced initial fading was observed in redness (a(*)) within the first 15 days in the VP samples and within the second month in the gas packaged samples attributed to the presence of white film on surface of CL portions. No differences were observed (p>0.05) in texture parameters evaluated between packaging methods during storage, and the values found are within the range for CL not packaged. The sensory properties of CL stored in 20/80% CO(2)/N(2) were slightly less acceptable than the samples packed under vacuum and under 80/20% CO(2)/N(2) at 210 days of storage. It is concluded that no clear advantage of the gas packaging was observed compared to the VP of "Cecina de Leon". PMID- 22063810 TI - Construction, management and cleanliness of red meat abattoir lairages in the UK. AB - A survey of a large number of UK abattoirs was conducted via a questionnaire designed to obtain information on (i) throughput and species slaughtered; (ii) construction materials used; (iii) use and type of bedding and (iv) details of cleaning/sanitation regimes. A representative group of abattoirs were selected on the basis of the responses to the questionnaire, and the lairage at these plants investigated through enumeration of Escherichia coli remaining after routine cleansing operations. The aim of this study was to enable identification of "common lairage practices" and to assess the general status of the lairage hygiene and effectiveness of lairage cleaning in commercial UK abattoirs. The study shows that microbial contamination often remains in UK lairage holding pens after routine cleaning operations. It would appear that there are significant differences in the effectiveness of lairage cleaning programmes at commercial abattoirs, and that the stun-box-roll-out areas are often cleaned to a better standard than the holding areas. As a result of persistence of microbial contamination in the lairage, there is a possible risk of foodborne pathogens persisting in the environment and potentially contaminating animals and carcasses processed on subsequent days. PMID- 22063811 TI - Accuracy of in vivo muscularity indices measured by computed tomography and their association with carcass quality in lambs. AB - Assessments of muscle mass and skeletal dimensions by Computed Tomography (CT) enable the development of new muscularity indices for the hind leg (HL) and lumbar region (LR) in lambs. Compared to previous CT muscularity indices, the accuracy was much higher with the new index in the HL (correlations between CT and dissection indices of 0.89 vs 0.51). The accurate measurement of femur length by CT used in the calculation of the new HL index made an important contribution to the higher accuracy of the index. The improvement in accuracy was smaller for the LR (0.55 vs 0.44). The association of CT muscularity indices and carcass quality in Texel and Scottish Blackface lambs showed that improved muscularity is not phenotypically correlated with detrimental effects on carcass composition. CT muscularity indices provide an alternative method to improve carcass conformation and leanness, using measurements that at a constant weight are independent of fatness. PMID- 22063812 TI - Effects of weight at slaughter and sex on the carcass characteristics of Florida suckling kids. AB - The effect of slaughter weight and sex on some carcass traits of suckling kids of the Florida breed was evaluated. A total of 60 kids (30 male and 30 female), fed exclusively on milk replacers, were slaughtered at 7-8kg (group 1), 10-11kg (group 2) or 14-15kg (group 3) of liveweight (mean weights of 7.6kg, 10.8kg and 14.4kg, respectively). Higher slaughter weights decreased the percentage of subproducts (blood, skin, head, feet) and internal organs (lungs+traquea, heart, liver, spleen, thymus) but significantly increased the percentage of intestine and fat depots (omental fat and mesenteric fat). Higher slaughter weights also increased carcass measures (L 40.5 vs 49.1; F 22.5 vs 25.9; G 10.4 vs 14.2; Wr 10.1 vs 13.9; Wth 8.0 vs 10.5; Th 16.5 vs 199; B 32.3 vs 42.4; PT 41.5 vs 50.8), compactness carcass index (96.6 vs 152.3) and compactness leg index (27.5 vs 44.1). Sex only significantly affected the percentages of feet, internal organs, omental fat, measure L, carcass compactness index and hind limb compactness index. The meat colour and fat colour were mainly scored as pale and white respectively in the carcasses of the lightest animals, whereas heavier kids were scored as pink and cream. Slaughter weight also influenced significantly the carcass fatness (score 1 in lightest kids and 2 or 3 in heavier ones). There were no significant (p>0.05) differences between slaughter weight group and sex in dressing percentages. Percentages corresponding to the long leg, back and neck (30-33%, 18-19% and 8-10%, respectively) decreased when the slaughter weight increased, whereas the ribs (23-25%) and the flank (10-11%) increased slightly. The carcasses comprised 57-58% muscle, 22-25% bone, 5-6% subcutaneous fat and 9 12% intermuscular fat. The percentage muscle stayed the same with increasing slaughter weight, whereas the bone decreased and the fat increased. The carcasses of the heavier females contained less lean and more fat than the males. The bone percentage was significantly (p<0.05) lower in the females and the carcass fat percentage was significantly (p<0.05) higher than in the males. PMID- 22063813 TI - Functional recovery after cerebellar damage is related to GAP-43-mediated reactive responses of pre-cerebellar and deep cerebellar nuclei. AB - Since brain injuries in adulthood are a leading cause of long-term disabilities, the development of rehabilitative strategies able to impact on functional outcomes requires detailing adaptive neurobiological responses. Functional recovery following brain insult is mainly ascribed to brain neuroplastic properties although the close linkage between neuronal plasticity and functional recovery is not yet fully clarified. The present study analyzed the reactive responses of pre-cerebellar (inferior olive, lateral reticular nucleus and pontine nuclei) and deep cerebellar nuclei after a hemicerebellectomy, considering the great plastic potential of the cerebellar system in physiological and pathological conditions. The time course of the plastic reorganization following cerebellar lesion was investigated by monitoring the Growth Associated Protein-43 (GAP-43) immunoreactivity. The time course of recovery from cerebellar symptoms was also assessed to parallel behavioral and neurobiological parameters. A key role of GAP-43 in neuronal reactive responses was evidenced. Neurons that underwent an axotomy as consequence of the right hemicerebellectomy (neurons of left inferior olive, right lateral reticular nucleus and left pontine nuclei) exhibited enhanced GAP-43 immunoreactivity and cell death. As for the not axotomized neurons, we found enhanced GAP-43 immunoreactivity only in right pontine nuclei projecting to the spared (left) hemicerebellum. GAP-43 levels augmented also in the three deep cerebellar nuclei of the spared hemicerebellum, indicating the ponto-cerebellar circuit as crucially involved in functional recovery. Interestingly, each nucleus showed a distinct time course in GAP-43 immunoreactivity. GAP-43 levels peaked during the first post-operative week in the fastigial and interposed nuclei and after one month in the dentate nucleus. These results suggest that the earlier plastic events of the fastigial and interposed nuclei were driving compensation of the elementary features of posture and locomotion, while the later plastic events of the dentate nucleus were mediating the recovered ability to flexibly adjust the locomotor plan. PMID- 22063814 TI - Language, memory and the temporal lobes. PMID- 22063815 TI - Taxonomic and thematic organisation of proper name conceptual knowledge. AB - We report the investigation of the organisation of proper names in two aphasic patients (NBC and FBI). The performance of both patients on spoken word to written word matching tasks was inconsistent, affected by presentation rate and semantic relatedness of the competing responses, all hallmarks of a refractory semantic access dysphasia. In a series of experiments we explored the semantic relatedness effects within their proper name vocabulary, including brand names and person names. First we demonstrated the interaction between very fine grain organisation and personal experience, with one patient with a special interest in the cinema demonstrating higher error rates when identifying the names of actors working in a similar film genre (e.g., action movies: Arnold Schwarzenegger, Bruce Willis, Sylvester Stallone, Mel Gibson) than those working in different genres (e.g., Arnold Schwarzenegger, Gregory Peck, Robin Williams, Gene Kelly). Second we compared directly two potential principles of semantic organisation - taxonomic and thematic. Furthermore we considered these principles of organisation in the context of the individuals' personal knowledge base. We selected topics matching the interests and experience of each patient, namely cinema and literature (NBC) and naval history (FBI). The stimulus items were arranged in taxonomic arrays (e.g., Jane Austen, Emily Bronte, Agatha Christie), thematic arrays (e.g., Jane Austen, Pride and Prejudice, Mr Darcy), and unrelated arrays (e.g., Jane Austen, Wuthering Heights, Hercule Poirot). We documented that different patterns of taxonomic and thematic organisation were constrained by whether the individual has limited knowledge, moderate knowledge or detailed knowledge of a particular vocabulary. It is suggested that moderate proper name knowledge is primarily organised by taxonomy whereas extensive experience results in a more detailed knowledge base in which theme is a powerful organising principle. PMID- 22063816 TI - Naming with proper names: the left temporal pole theory. AB - Existing empirical data on proper names processing are critically reviewed in trying to understand which tasks may involve the left temporal pole, which proper name related functions are supported by this structure and eventually offer some speculations about why these functions might have developed in this location in the course of human evolution. While clinical group studies support the idea that proper name processing takes place in the left temporal pole, single case studies of selective proper name anomia or sparing, as well as neuroimaging studies, suggest the involvement of a larger neural network. Within this network, an important role may be played by the ventro-medial prefrontal cortex, including areas critical in social interaction. The differentiation in the brain of proper name processing from common names processing could in part be due to social pressure, favouring a neural system able to more efficiently and unambiguously sustain designating categories or designating individual entities. The activation of the left temporal pole in proper name processing is shown to increase with age. Longer social interaction may thus contribute to convey proper names processing toward areas closer to those supporting social cognition. PMID- 22063817 TI - The executive control of face memory. AB - Patients with frontal lobe damage and cognitively normal elderly individuals demonstrate increased susceptibility to false facial recognition. In this paper we review neuropsychological evidence consistent with the notion that the common functional impairment underlying face memory distortions in both subject populations is a context recollection/source monitoring deficit, coupled with excessive reliance on relatively preserved facial familiarity signals in recognition decisions. In particular, we suggest that due to the breakdown of strategic memory retrieval, monitoring, and decision operations, individuals with frontal lobe impairment caused by focal damage or age-related functional decline do not have a reliable mechanism for attributing the experience of familiarity to the correct context or source. Memory illusions are mostly apparent under conditions of uncertainty when the face cue does not directly elicit relevant identity-specific contextual information, leaving the source of familiarity unspecified or ambiguous. Based on these findings, we propose that remembering faces is a constructive process that requires dynamic interactions between temporal lobe memory systems that operate in an automatic or bottom-up fashion and frontal executive systems that provide strategic top-down control of recollection. Executive memory control functions implemented by prefrontal cortex play a critical role in suppressing false facial recognition and related source memory misattributions. PMID- 22063818 TI - The causes and consequences of transient epileptic amnesia. AB - Transient epileptic amnesia (TEA) is a recently recognised syndrome of epilepsy in which the principle manifestation of seizures is recurrent episodes of isolated memory loss. In this article, we describe the clinical and cognitive profile of this emerging syndrome, and present new data that provide at most weak support for its proposed relationship to cerebrovascular disease. TEA is often associated with two unusual forms of interictal memory impairment: accelerated long-term forgetting and remote memory impairment. We discuss the clinical and theoretical implications of these relatively novel cognitive deficits. PMID- 22063819 TI - Distorted temporal consciousness and preserved knowing consciousness in confabulation: a case study. AB - In this study we describe a patient, TA, who developed a chronic amnesic confabulatory syndrome, following rupture of a right internal carotid siphon aneurysm. Our aim was to elucidate as fully as possible the nature of TA's impairment and to test the hypothesis of confabulation as reflecting a dysfunction of Temporal Consciousness, i.e., to become aware of something as part of a personal past, present or future. TA's confabulations were present in answers to questions tapping Temporal Consciousness, i.e., autobiographical episodic memory, orientation in time and place, and foresight of personal future. In contrast, confabulations were not observed in answers to questions tapping Knowing Consciousness, i.e., to become aware of something as a meaning or as an element of impersonal knowledge. In fact, he had normal access to semantic knowledge, including foresight of impersonal future. TA's brain MRI showed lesions involving the right hippocampus, parahippocampal gyrus, fornix, mammillary bodies, and thalamus. Moreover TA showed sub-cortical lesions involving the caudate and putamen nuclei bilaterally, a lesion site not commonly described in amnesic-confabulatory syndrome. We suggest that this pattern of results is better accounted for within the framework of the Memory, Consciousness and Temporality Theory and reflects a specific distortion of Temporal Consciousness. PMID- 22063820 TI - Therapy efficacy in chronic aphasia. AB - There is good evidence that aphasia therapy is effective if sufficiently prolonged or intensive and that chronic aphasic individuals can also benefit from therapy, but data on chronic aphasia are scanty. The aim of this retrospective study was to investigate whether chronic aphasia benefits from a very intensive therapeutic regimen. We revised the files (January 2000 to December 2008) of the chronic subjects whom we suggested have periodic sessions in our Unit (generally once a week) and 2-3 hours daily of homework with the help of a family member, supervised and controlled by the speech-therapist. Treatment would go on as long as amelioration is evident. Results for 23 chronic aphasic subjects are reported. All subjects had undergone previous therapy and 10 had been dismissed because no further recovery was expected. Recovery was significant in oral and written nouns and actions naming, oral and written sentence production and Token Test scores. Only 4 subjects did not improve. Severity of the disorder did not predict success or failure. We conclude that recovery was due to the intense work done. Further, we believe such a regimen could be successful in a number of patients for whom a less intensive regimen would not be effective. PMID- 22063822 TI - Biased mutational pattern and quasispecies hypothesis in H5N1 virus. AB - Like other RNA viruses, influenza viruses are subject to high mutation rates. Carrying segmented RNA genomes, their genetic variability is even higher. We aimed at analyzing the mutational events occurring during the infection of chickens by the Highly Pathogenic Avian Influenza (HPAI) H5N1 virus. We therefore studied the different sequences of two surface proteins, hemagglutinin (HA) and neuraminidase (NA), as well as two internal proteins, PB2 and NS. Three organs (lung, spleen, brain) were obtained from a chicken, experimentally infected with a lethal dose of HPAI H5N1 virus. Cloning these PCR fragments enabled us to investigate the mutations undergone by the virus after several replicative cycles. The first outcome is the presence of a strong mutational bias, resembling host-driven ADAR1 adenosine deamination, which is responsible for 81% of all mutations. Whereas the frequency of RNA dependent RNA polymerase-related mutations is compatible with the survival of the virus, the ADAR1-like activity usually strongly increases the mutation frequency into a level of "error catastrophe" in theory incompatible with virus survival. Nevertheless, the virus was successfully infective. HPAI H5N1 virus displayed traits in agreement with the quasispecies theory. The role of this quasispecies structure in successful infection and the superposition with the ADAR1-like response is discussed. PMID- 22063824 TI - The World Cancer Research Fund report 2007: A challenge for the meat processing industry. AB - One of the 10 universal guidelines for healthy nutrition in a report of the World Cancer Research Fund released at the end of 2007 is to "limit intake of red meat and avoid processed meat", as a result of the "convincing evidence" for an association with an increased risk of colorectal cancer development. In the present paper, the scientific evidence for the association between processed meats intake and colorectal cancer development is explored and the most probable hypothesis on the mechanism underlying this relationship formulated. It seems that the present state of knowledge is not well understood but relates to a combination of haem iron, oxidative stress, formation of N-nitroso compounds and related residues in the digestive tract as the causal factors. Although criticisms of the inaccurate definition of processed meats and the insufficient accounting for the large variability in composition of meat products have been expressed, it is clear that the report urges proper action by the meat and nutrition research community and the meat industry. Research items that in our view should be addressed are discussed. They include: (1) evaluating the health risks associated with processed meats intake within the context of the supply of beneficial nutrients and other nutrition associated health risks; (2) definition of the role of nitrites and nitrates in meat processing; (3) investigating the role of red and processed meats on the endogenous formation of N-nitroso compounds in the digestive tract; and (4) developing improved processed meats using new ingredients. PMID- 22063825 TI - Collagen contribution to meat toughness: Theoretical aspects. AB - One of the major changes in connective tissues during heating is the transformation of the quasi-crystalline structure of collagen into a random-like structure. This molecular change induces a shortening of these tissues and gives them a rubber-like behaviour. In this state, their mechanical properties are dependent on the total number of cross-linked chains present per volume, which can be estimated from the number and the functionality of each cross-link present in the sample. The number of cross-linked chains per volume of meat explains a large amount of the tenderness variation, produced by muscle type, animal age, type, and sex in different species. During heating collagen fibres and fibrils shortening produces a pressure which is also dependent on the total amount of cross-linked chains present per volume, but also on the morphology of endomysial and perimysial envelopes. In meat, during heating, collagen fibres and fibrils thermal shortening is restricted by muscle fibres and muscle fibre bundles. This restriction, which depends on several muscle fibre characteristics, has a strong effect on the final elastic modulus of connective tissues, by changing the respective amount of crystalline and rubber-like fractions in collagen fibres and fibrils after heating. The implications of this phenomenon in tenderness variations are discussed. PMID- 22063826 TI - Pig Longissimus lumborum proteome: Part I. Effects of genetic background, rearing environment and gender. AB - A 2*2*2 factorial experiment on Longissimus lumborum of 24 pigs found that rearing environment (indoors or outdoors), breed of sire (Duroc or Large White), and gender (female or castrated male) influenced 22, 10, and 88 proteins of the soluble fraction, respectively, containing 220 matched spots in total. Some proteins were influenced by more than one main effect. Outdoor rearing resulted in lower levels of enzymes of the glycolytic pathway suggesting a more oxidative metabolism. Breed of sire slightly altered the balance of enzymes of the glycolytic pathway. Gender had profound effects. In particular, different enzyme levels suggest a more lipid oriented energy metabolism, and a higher extractability of myofibrillar proteins suggest altered control of the contractile apparatus, in castrated males. Differences in extractability did not explain the profound gender effects. Glycogen content, ultimate pH, drip and thawing losses showed main or interactive effects of the three treatment factors. PMID- 22063827 TI - Pig Longissimus lumborum proteome: Part II: Relationships between protein content and meat quality. AB - Gender, rearing environment and breed of sire influenced 50.5% of the matched protein spots of the soluble fraction and some meat quality traits [Kwasiborski, A., Sayd, T., Chambon, C., Sante-Lhoutellier, V., Rocha, D., & Terlouw, C. (2008). Muscle proteome in pigs: Part I: Effects of genetic background, rearing environment and gender. Meat Science]. Multiple regression analyses determined that 1 or 2 proteins explained between 24% and 85% of variability in Longissimus meat quality. Regression models differed between treatment groups, but relationships between proteins and meat quality traits seemed to be related to common underlying mechanisms. Thus, proteins retained in models for ultimate pH, lightness, drip, thawing and cooking loss were related to the glycolytic pathway, phosphate transfer, or fibre type composition. Another model for thawing loss retained proteins related to denaturation of myofibrils or lipid content. The models for redness involved proteins related to post-mortem oxidative activity. Thus, proteins correlated with meat quality traits were related to biochemical mechanisms known to be involved in meat quality. Relative contributions of these mechanisms may vary according to gender, sire breed or rearing environment. PMID- 22063828 TI - Antioxidant properties of plum concentrates and powder in precooked roast beef to reduce lipid oxidation. AB - Boneless beef roasts (Semimembranosus+Adductor) were injected (20%) with a brine containing (1) no plum ingredient (control), (2) 2.5 or 5% fresh plum juice concentrate (FP), (3) 2.5 or 5% dried plum juice concentrate (DP), or (4) 2.5 or 5% spray dried plum powder (PP). Whole roasts were cooked, vacuum-packaged and stored at <4.0 degrees C for 10wk. At 2wk intervals, evaluations were performed on sliced product to determine vacuum-packaged purge, Allo-Kramer shear force, lipid oxidation (TBARS), color space values, and sensory attributes. All plum ingredients reduced TBARS values and had minimal effects on tenderness, sensory characteristics, color and appearance. Small changes in purge, color values, TBARS and some sensory properties were found during storage. These results indicate that 2.5% FP or DP could be incorporated into precooked beef roasts to reduce lipid oxidation and potentially, warmed-over flavor (WOF). PMID- 22063829 TI - Beliefs and attitudes of butchers and consumers towards dry-cured ham. AB - The objectives were to evaluate the attitude of butcher and consumer towards soft and pasty texture problems in dry-cured ham and to assess the butcher and consumer behaviour when selecting and purchasing this product. Ninety-nine butchers and 200 consumers were interviewed with 17-question and 20-question surveys, respectively. The texture problems (softness and pastiness) were highly important for both butchers and consumers. The characteristics most frequently considered "important" or "very important" by butchers were processing time, smell/aroma and texture as selection criteria and salty taste and aged/matured flavour as sensory indicators of dry-cured ham quality. According to butchers' opinion, salty taste and their own advice are the factors most frequently considered "important" or "very important" as affecting the consumer's decision to purchase. For the consumer, the sensory attributes were considered more important than extrinsic characteristics when purchasing dry-cured ham. PMID- 22063830 TI - Consumers' sensory acceptability of pork from immunocastrated male pigs. AB - Boar taint is the off-odour or off flavour of cooked pork. Currently, the most common method of controlling boar taint is surgical castration. However, immunocastration has been used in some parts of the world as an alternative to surgical castration. The aim of this study was to evaluate the sensory acceptability of meat from immunocastrated pigs (IM) compared with meat from females (FE), surgically castrated (CM) and entire males (EM). Twenty animals of each type were evaluated by 201 consumers in 20 sessions. Longissimus thoracis muscle of the different animals was cooked in an oven at 180 degrees C for 10min. Consumers scored the odour and the flavour of the meat in a 9-point category scale without an intermediate level. There were no significant differences in consumer's evaluation of meat from IM, CM, and FE. In contrast, EM meat presented a higher percentage of dissatisfied scores and was significantly (P<0.05) less accepted than meat from CM, IM and FE. Consumers' acceptability of EM meat was always lower, independently of its androstenone levels. However meat with low levels of androstenone was more accepted that meat with medium or high levels of this substance. It can be concluded that immunocastration produced pork that was accepted by the consumers, and was indistinguishable from pork from CM or FE. PMID- 22063831 TI - Meat quality of Moxoto and Caninde goats as affected by two levels of feeding. AB - The objective of this study was to evaluate the effect of reduced feed intake on Moxoto and Caninde goat, which are native breeds of semi arid area of Brazil, by analyzing the resultant meat quality. Intact male goats of both genotypes (10 animals each), weighing about 15kg, were allocated to two feeding levels (AL: feed ad libitum and FR: feed restricted to 63% of the total feed consumed by AL). Water-holding capacity and a(*) color parameter were significantly influenced (p<0.05) by genotype. Proximate composition, cholesterol, shear force, pH, cooking loss, and sensory scores did not differ significantly (p>0.05) between genotypes. The redness of the meat of the Caninde breed was much improved in FR goats. Although, feed restriction by 37% did affect the final live weight and mean daily gain weight, it had no effect on chemical, physical, and sensory quality of Moxoto and Caninde meat. PMID- 22063832 TI - Comparison of the thermal characteristics of connective tissue in loose structured and normal structured porcine M. semimembranosus. AB - The aim of the present study was to characterise the thermal properties of connective tissue in loose structured porcine SM muscles in comparison to normal looking SM muscles and to see whether the meat quality traits were related to the properties of connective tissue. Samples from the muscles with loose structure and light colour were selected by visual assessment and normal looking SM muscles were used as a control (n=25 loose structured+25 control). The loose structured muscles had lower ultimate pH (pH(u)) than the control muscles. The onset and peak temperatures of thermal shrinkage of intramuscular connective tissue (T(o) and T(p), respectively) in loose structured muscles were similar to those of control muscles when the full set of data (25 loose structured+25 control) were analysed. When the T(o) and T(p) data from muscles the exhibiting ten lowest and ten highest pH(u) values were analysed, the low pH(u) muscles (all classified as loose structured) had lower T(o) and T(p) than the high pH(u) muscles (all classified as control) (p<0.05). Drip loss of loose structured SM muscles (11.1%) was dramatically higher than that of control muscles (3.9%). Collagen content and collagen solubility were similar in loose structured and control muscles. It seemed that changes in the properties of intramuscular connective tissue were more easier found in porcine SM muscles with low pH(u) than in SM muscles with high pH(u). PMID- 22063833 TI - The assessment of carcass composition of Awassi male lambs by real-time ultrasound at two different live weights. AB - The accuracy of ultrasonography to measure fat thickness (FT) and longissimus dorsi muscle (LM) traits (area, depth and width) in live Awassi male lambs and predict carcass FT and LM traits was studied. Twenty six Awassi male lambs were randomly divided into light (L) (n=13) and heavy (H) (n=13) finishing lambs. Slaughter weight of lambs in L and H groups were 40 and 45kg, respectively. FT and LM traits, cross-sectional area between the 12th and 13th rib were measured using real-time ultrasound in vivo and on the carcass after slaughter. All ultrasound and carcass measurements were the same except live weight (LW) (P<0.001), cold carcass weight (CCW) (P<0.001) and carcass LM width (P<0.05). Overall, correlation coefficients between ultrasound and carcass FT, LM depth, width and area were 0.79, 0.82 (P<0.001); 0.60, 0.58 (P<0.05); 0.48, -0.17 (P>0.05) and 0.89, 0.87 (P<0.001), respectively, for lambs in L and H groups. The introduction of ultrasound FT and ultrasound LM area as independent variables in addition to LW in the multiple regression equations further improved the variations for carcass FT (84%, 71%), carcass LM area (79%, 79%), CCW (72%, 65%) for lambs in light and heavy groups whereas no improvement was observed for carcass yield. These results indicate that in vivo ultrasound FT and measurement of the LM area in association with LW could be used to estimate carcass FT, carcass LM area and CCW in different LW Awassi lambs. PMID- 22063834 TI - Feeding strategy for improving tenderness has opposite effects in two different muscles. AB - Compensatory growth has been shown to affect rate of muscle protein turnover and may potentially improve tenderness of beef. Thus, a study of tenderness in relation to feeding regime and slaughtering at a time with maximal muscle protein degradation was performed. Friesian bull calves (5-month-old) were fed either ad libitum (n=6) (AA) or restrictively for 3 months followed by re-alimentation for 6 weeks (n=6) (RA) before slaughter at 10 months. At slaughter the fractional breakdown rate of muscle protein was 2.4% in RA compared with 1.6% in AA (P<0.06). Sensory profiling revealed superior texture of M. semimembranosus from RA compared with AA, whereas M. longissimus was superior in texture from AA compared with RA, with no difference in proteolysis and shear force. In conclusion it was clear that different muscles in terms of tenderness responded very differently to the nutritional manipulation. PMID- 22063835 TI - Enhancement of the nutritional status and quality of fresh pork sausages following the addition of linseed oil, fish oil and natural antioxidants. AB - Fresh pork sausages (pork shoulder, pork back fat, water, rusk and seasoning) were manufactured where 15% of the pork back fat was substituted with linseed oil (LO) or fish oil (FO). Green tea catechins (GTC) and green coffee antioxidant (GCA) were added to both LO (LGTC 200 and LGCA 200) and FO (FGTC 200 and FGCA 200) substituted sausages at a level of 200mg/kg. Raw and cooked pork sausages were either over-wrapped with oxygen permeable film (aerobic storage) or stored in modified atmosphere packages (MAP) containing 80% O(2):20% CO(2) or 70% N(2):30% CO(2), respectively for 7 days at 4 degrees C. Effects on fatty acid profiles, lipid oxidation, colour and sensorial properties were investigated. alpha-Linolenic acid increased from 1.34% (control) to 8.91% (LO) and up to 11.2% (LGTC 200 and LGCA 200). Addition of fish oil increased levels of EPA from 0.05% (control) to 2.83% (FO), 3.02% (FGTC 200) and 2.87% (FGCA 200) and DHA levels increased from 0.04% (control) to a maximum of 1.93% (FGTC 200). Lipid oxidation was low in raw and cooked linseed oil containing sausages. GTC (200mg/kg) significantly (P<0.05) reduced lipid oxidation in raw fish oil containing sausages after 7 days of storage. Colour parameters in raw pork sausages were unaffected by the packaging atmosphere. L(*) lightness values were lower (P<0.05) in LGTC 200 and a(*) redness values lower (P<0.05) in LGTC 200 and FGTC 200 after 7 days of storage. Sensory scores of cooked pork sausages were unaffected by linseed oil addition. Flavour and overall acceptability scores in cooked fish oil containing sausages were improved by GTC addition. Results obtained demonstrate potential for the production of nutritionally enhanced fresh pork sausages. PMID- 22063836 TI - Sensory and preference testing of selected beef muscles infused with a phosphate and lactate blend. AB - Consumers expect beef products to be juicy and tender. In the present investigation four beef muscles, i.e. Biceps femoris (BF), Longissimus lumborum (LL), Rectus femoris (RF) and Semitendinosus (ST), were infused with a blend consisting of sodium and potassium salts, di- and triphosphates and lactates. The muscles were stored at 4 degrees C for 24h, followed by storage at -18 degrees C until the descriptive sensory analysis could be performed on all four muscles. BF and LL were also subjected to consumer sensory analysis to determine the overall degree of liking. The infused and non-infused samples did not differ significantly with regard to aroma and flavour. The infused samples were significantly more juicy and tender than the untreated samples. Although the infused samples were rated significantly higher in salty taste than the untreated samples, both treatments illustrated a relatively low mean value for saltiness. Both the infused LL and BF samples illustrated a high degree of liking. Therefore, the infusion of beef muscles with a blend containing phosphates and lactates could be applied successfully to enhance the sensory attributes of beef. PMID- 22063837 TI - Effect of live weight and sex on physico-chemical and sensorial characteristics of Merino lamb meat. AB - Forty-eight lamb carcasses were divided into four groups (n=12) according to slaughter weight (24 and 29kg) and sex (male and female). Colour, pH, moisture, and intramuscular fat were not affected (p>0.05) by slaughter weight or sex. With respect to fatty acid composition, slaughter weight had significant effects on C12:0 (p<0.01), C14:0, C16:0, and C18:1 n-9 (p<0.05) in Longissimus lumborum (LL) muscle. The percentage of C12:0 and C14:0 decreased as slaughter weight increased, while C16:0 increased. In Semimembranosus (SM) m., only C18:3 n-3 and C20:2 n-6 were affected (p<0.001) by slaughter weight. Total PUFA in LL m. was greater (p<0.01) in females than in males. Although in general, sensorial quality was not significantly affected by slaughter weight or sex, meat from lighter lambs (24kg) had greater general acceptability than meat from heavier lambs (29kg). PMID- 22063838 TI - Proteins in longissimus muscle of Korean native cattle and their relationship to meat quality. AB - Proteomic profiling by two-dimensional gel electrophoresis and mass spectrometry of longissimus dorsi muscle tissue from Korean native cattle identified seven proteins that are differentially expressed in animals producing low and high quality grade beef. The expression level of alpha actin is increased in high quality grade beef and the expression levels of T-complex protein 1 (TCP-1), heat shock protein beta-1 (HSP27), and inositol 1,4,5-triphosphate receptor type1 (IP3R1), a new protein to be associated with meat quality, are increased in low quality grade beef. In particular, the quantitation of HSP27 and IP3R1 by both silver staining and immunoblotting correlated well with intramuscular fat content, meat tenderness, and free calcium levels. The data suggest that HSP27 and IP3R1 are potential meat quality biomarkers and their identification provides new insight into the molecular mechanisms and pathways associated with overall beef quality. PMID- 22063839 TI - Effect of the inoculation of a starter culture and vacuum packaging during the resting stage on sensory traits of dry-cured ham. AB - The effects of the inoculation of a mixed starter culture and vacuum packaging (during resting stage) on odour, appearance, texture and flavour of dry-cured ham were studied. After salting, half of the 36 processed hams were inoculated with a commercial starter culture containing lactic-acid bacteria, Gram-positive catalase-positive cocci and yeasts. Nine hams per group (inoculated and non inoculated) remained vacuum-packaged during resting. External odour during the process, as well as appearance of the cut surface, texture and flavour on semimembranosus and biceps femoris of the final product were assessed. Vacuum packaging during resting caused an increase in white film and feedstuff flavour, as well as a decrease in aged flavour, hardness, fibrousness and overall liking. The use of the starter culture brought about an increase in feedstuff flavour, a decrease in sweetness, aged flavour, nutty flavour and overall liking and, only in vacuum-packaged hams, the development of a floral flavour, but had no significant effect on texture descriptors. The starter culture studied is considered inappropriate for the production of traditional Spanish dry-cured ham regardless of the type of resting used. PMID- 22063840 TI - Application of a radical scavenging activity test to measure the total antioxidant activity of poultry meat. AB - The antioxidant activity of the hydrophilic and lipophilic fraction of poultry meat was determined in terms of 'radical scavenging activity' (RSA) using a modified ABTS radical cation decolorization method. The method uses the extraction of hydrophilic and lipophilic fractions in water and methanol chloroform, respectively. The determination of the RSA of the lipophilic fraction was conducted using a chloroform extract and maintaining a constant chloroform:ethanol ratio in the solution of analysis. The method was tested on nine samples of poultry breasts and thigh meats and permitted to quantify the RSA in terms of MUmol Trolox equivalent antioxidant capacity (TEAC) with a mean relative standard deviation of less than 5%. The contribution of the hydrophilic fraction to the total RSA was much higher than that of the lipid soluble fraction. Breast showed a higher RSA than thigh meat due to its lower total lipids content. The total RSA value (TEAC=2.4MUmolg(-1)) suggests that poultry meat could significantly contribute to the antioxidant activity of the diet. PMID- 22063841 TI - Extension of the display life of lamb with an antioxidant active packaging. AB - Fresh lamb steaks were treated with three different preparations of natural antioxidants: one group was packaged with a rosemary active film, the second group was packaged with an oregano active film, and the third group was sprayed on the meat surface with a rosemary extract before packaging in a high-oxygen atmosphere. Samples were stored under illumination at 1+/-1 degrees C for 13days. Metmyoglobin formation, lipid oxidation (TBARS), instrumental colour (CIE a(*)), psychrotrophic bacterial counts (PCA), sensory discolouration and off-odour were determined. The use of a rosemary extract, a rosemary active film or an oregano active film resulted in enhanced oxidative stability of lamb steaks. Active films with oregano were significantly more efficient than those with rosemary, exerting an effect similar to that of direct addition of the rosemary extract; in fact, they extended fresh odour and colour from 8 to 13days compared to the control. PMID- 22063842 TI - Beef sausage structure affected by sodium chloride and potassium lactate. AB - A histological and ultrastructural study was conducted to characterize changes in the muscle fibre structure of three fresh sausage preparations, depending on meat composition, sodium chloride (NaCl) and potassium lactate (K-lactate) contents. After addition of 0.8% and 1.6% NaCl, 65% and 51%, respectively, of the area observed showed well preserved fibres (histological data). The altered regions presented a large disorganization of the myofilaments and a solubilization of the sarcolemma and of the Z lines. K-lactate addition had no marked effects on meat structure. The preparation containing some sheep meat was more sensitive to salt than the others containing only bovine meat. The level of alteration was much lower than those obtained in pork meat in another study. Technological conditions used to modify the internal muscle fibre structure during sausage processing depend on the species used. Therefore, the classification of the sausage preparation to "meat preparation" or "meat product" under the EU regulation (EC) No. 853/2004 (which assign meat preparations to meat if the product has undergone a process insufficient to modify the internal muscle fibre structure of the meat) must be systematically controlled when changing the meat sausage composition. PMID- 22063843 TI - Effects of previous diet and duration of soybean oil supplementation on light lambs carcass composition, meat quality and fatty acid composition. AB - Forty Merino Branco ram lambs were used to study the effects of initial diet and duration of supplementation with a conjugated linoleic acid (CLA) promoting diet, on carcass composition, meat quality and fatty acid composition of intramuscular fat. The experimental period was 6 weeks. The experimental design involved 2 initial diets (commercial concentrate (C); dehydrated lucerne (L)), and 2 finishing periods (2 and 4 weeks) on dehydrated lucerne plus 10% soybean oil (O). Data were analysed as a 2*2 factorial arrangement with initial diet and time on finishing (CLA promoting) diet as the main factors. The lambs were randomly assigned to four groups: CCO; COO; LLO; LOO according to the lamb's diet fed in each period. Lambs initially fed with concentrate showed higher hot carcass weights (11.2 vs 9.6kg) than lambs fed initially with lucerne. The increase of the duration of finishing period reduced the carcass muscle percentage (57.4% vs 55.5%) and increased the subcutaneous fat percentage (5.67% vs 7.03%). Meat colour was affected by initial diet. Lambs initially fed with concentrate showed a lower proportion of CLA (18:2cis-9, trans-11 isomer) (0.98% vs 1.38% of total fatty acids) and most of n-3 polyunsaturated fatty acids than lambs initially fed with lucerne. Initial diet did not compromise the response to the CLA-promoting diet and the proportion of 18:2cis-9, trans-11 in intramuscular fat increased with the duration of time on the CLA-promoting diet (1.02% vs 1.34% of total fatty acids). PMID- 22063844 TI - The effect of interaction between genotype CAST/RsaI (calpastatin) and MYOG/MspI (myogenin) on carcass and meat quality in pigs free of RYR1(T) allele. AB - The purpose of the studies was to demonstrate to what degree genotypes of calpastatin (CAST/RsaI) and myogenin (MYOG) genes as well as the interaction between them may affect the carcass and meat quality of pigs. The investigations were conducted on 397 stress resistant pigs (free of RYR1(T) allele). It was demonstrated that the favourable effect of the variants of CAST and MYOG genes on carcass quality traits depends on the cut. The gene variant favourably affecting the weight of ham simultaneously had a negative effect on the weight of the loin. It was also shown that the interaction between CAST and MYOG genotypes has a significant effect on backfat thickness. The effect of a given combination of CAST and MYOG genotypes on carcass traits is related to the weight of a substantial cut (ham, loin). Genotypes at loci CAST/RsaI and MYOG have a significant effect on the value of certain traits and parameters of meat quality and its technological value (genotype CAST on pH at 35min and 2, 3, 24, 48, 96, 144h post-mortem (pH(35), pH(2), pH(3), pH(24), pH(48), pH(96), pH(144), respectively), R(1) (IMP/ATP), electrical conductivity at 3 and 4h post-mortem (EC(3), EC(4)), technological yield of meat in curing and thermal processing (TY) and protein content in the muscle tissue, while genotype MYOG on pH(48), EC(35), EC(3), EC(24) and dry matter content). PMID- 22063845 TI - Effects on growth performance, carcass characteristics, and the fat and meat fatty acid profile of rabbits fed diets with chia (Salvia hispanica L.) seed supplements. AB - The effects of three levels (0%, 10%, or 15%) of chia (Salvia hispanica L.) seed (SHS) included in the diet on the growth performance, some carcass characteristics and fatty acid profile of rabbit meat and perirenal fat was studied. At the end of the experiment, there were no significant differences among the groups in live weight, live weight gain, feed consumption, feed efficiency, carcass yield or the percentages of edible organs. The percentage values of hind legs, fore legs, loin and abdominal wall, breast and ribs, skin and limbs, and head were not affected by the inclusion level of SHS. The polyunsaturated fatty acid (PUFA) concentration in the longissimus dorsi muscle and perirenal fat was significantly increased with increasing SHS inclusion, while the saturated fatty acid (SFA) decreased. The n-6/n-3 PUFA ratio of the rabbit meat decreased from 4.55 in the control group, to 1.03 in the 15% SHS group. PMID- 22063846 TI - Effect of gender and castration of females and slaughter weight on performance and carcass and meat quality of Iberian pigs reared under intensive management systems. AB - A total of 360 Iberian dam*Duroc sire pigs was used to study the influence of gender and castration of females (CM, castrated males; CF, castrated females; IF, intact females) and slaughter weight (SW; 145 and 156kg body weight, BW) on performance and carcass and meat quality. Each treatment was replicated four times (15 pigs). Intact females ate less, tended to have better feed conversion and had less carcass fat and more primal cuts yield than CM and CF. Pigs slaughtered at 156kg BW ate more feed and had worse feed conversion than pigs slaughtered at 145 BW. An increase in SW improved carcass yield, but tended to decrease trimmed ham yield. Intact females are an alternative to castrated females for intensive production of Iberian pigs. Also, the reduction in slaughter weight from 156 to 145kg BW is recommended for this type of production. PMID- 22063847 TI - Detection of virulence determinants by real time PCR in E. coli isolated from mutton. AB - Ninety three Escherichia coli isolates belonging to 35 serotypes isolated from market mutton were tested to find out the prevalence of virulence determinants, Verotoxin 1 (VT1), Verotoxin 2 (VT2), Intimin (eae) genes and enterohemolysin production. Real Time PCR based detection was carried out for virulence genes using SYBR green format and amplicons were confirmed by melt curve analysis. Prevalence of VT1 gene in these isolates was much higher (38.70%) on the other hand, that of VT2 gene was nil (0%) while that of eae was very low (3.22%). Enterohemolysin production was found in 31.18% isolates when tested on washed sheep blood agar supplemented with CaCl(2). All enterohemolysin producing isolates were also positive for the VT1 gene. PMID- 22063848 TI - The behaviour of the protein complex throughout the technological process in the production of cooked cold meats. AB - Protein composition was examined in order to find markers that could be useful in technology optimization. The behaviour of sarcoplasmic and myofibrillar proteins during the processing of roast pork was studied at the various processing steps, utilising some electrophoretic (SDS-PAGE, 2DE and IEF) and thermometric (DSC) techniques and evaluating the content of amino acids produced. The relevance of desmin as a marker of structural modification was emphasised. The extraction of myofibrillar proteins by brine, the formation of a protein network at 62 degrees C and the evaluation of the exudate produced during cooking are the crucial steps that should be monitored when a new industrial process is to be optimised. PMID- 22063849 TI - The use of various live animal measurements to predict carcass and meat quality in two divergent lamb breeds. AB - Live weight, subjective scores of condition and conformation, live animal video image analysis (LVIA), ultrasound and X-ray computed tomography (CT) scanning were used to investigate the best method or combination of methods for predicting carcass and meat quality traits in live Texel and Scottish Blackface lambs. Predictors derived from CT alone accounted for a high proportion of the variance in dissected fat and muscle weight in Texel lambs (adjusted R(2)=~0.8), as well as intra-muscular fat content in the loin (~0.6), but lower proportions in Blackface lambs (~0.7 for fat, 0.4-0.5 for muscle and intra-muscular fat), after adjusting for sire and fixed effects. Adding traits measured by other in vivo methods increased prediction accuracies (adjusted R(2)) by up to 0.26, depending on trait and data set. Shear force and ultimate pH could not be accurately predicted using the traits considered here (adjusted R(2)<0.4). Although the same methods tended to be best for predicting product quality traits between breeds, prediction accuracies differed. PMID- 22063850 TI - Chitosan effects on quality properties of Greek style fresh pork sausages. AB - The effect of chitosan (0.5% and 1%) added individually or in combination with nitrites (150ppm) on microbiological (Total Viable Counts, Lactic acid bacteria, Pseudomonas spp., Brochothrix thermosphacta, Enterobacteriaceae, yeasts and moulds), physicochemical-chemical (pH, chemical composition, lipid oxidation) and sensory properties of fresh pork sausages stored at 4 degrees C for 28 days was investigated. Chitosan addition resulted in significant (p<0.05) inhibition of microbial growth, while nitrites did not seem to protect sausages from microbial spoilage. A gradual reduction of nitrites was observed till the end of storage, when nitrites were almost depleted in all nitrite containing samples. The rate of lipid oxidation in fresh pork sausages was significantly decreased (p<0.05) by addition of increasing levels of chitosan, while samples containing both chitosan and nitrites showed the lowest malondialdehyde (MDA) values, indicating a synergistic antioxidative effect. Consequently, the samples containing the combination of nitrites and chitosan at any level deteriorated less rapidly and were judged as more acceptable than all the other samples. PMID- 22063851 TI - Comparison of visible and near infrared reflectance spectroscopy to discriminate between pasture-fed and concentrate-fed lamb carcasses. AB - We compared visible and near infrared spectroscopy to distinguish pasture-fed (P) from stall concentrate-fed (S) lamb carcasses. A total of 120 P and 139 S lambs were used. The reflectance spectrum of perirenal fat was measured at wavelengths between 400 and 700nm using a portable spectrophotometer, and at wavelengths between 400 and 2500nm using a laboratory monochromator NIRSystem. In method W(450-510), the reflectance data were used at wavelengths between 450 and 510nm. In methods W(400-700) and W(400-2500), a multivariate analysis was performed over the full set of reflectance data, at wavelengths in the range 400-700nm and 400 2500nm, respectively. The proportion of correctly classified P lambs was 89.1%, 90.8% and 97.5% for W(450-510), W(400-700) and W(400-2500,)W(400-2500) performing best. The proportion of correctly classified S lambs was not significantly different between methods (98.6%, 98.6% and 97.8% for W(450-510), W(400-700) and W(400-2500), respectively). PMID- 22063852 TI - Effect of feeding fermentable fibre-rich feedstuffs on meat quality with emphasis on chemical and sensory boar taint in entire male and female pigs. AB - Skatole, androstenone and other compounds such as indole cause boar taint in entire male pork. However, female pigs also produce skatole and indole. The purpose of this experiment was to minimise boar taint and increase overall impression of sensory quality by feeding entire male and female pigs with fibre rich feedstuffs. The pigs have been fed three organic diets for either 1 or 2 weeks prior to slaughter of which two diets contained different fermentable fibre rich feedstuffs - 10-13.3% dried chicory roots or 25% blue lupines. These two treatments were compared with pigs fed with an organic control diet for either 1 or 2 weeks prior to slaughter. Lupines significantly reduced skatole in blood and backfat for both genders after 1 week. Moreover, lupines showed negative impact on growth rate and feed conversion whilst chicory showed no significant differences in this respect. However, the indole concentration was significantly lower in chicory than lupine fed pigs. From a sensory perspective, chicory and lupine feeding reduced boar taint since odour and flavour of manure related to skatole and urine associated to androstenone were minimised. The level of boar taint in the entire male pigs was most effectively reduced after 14 days by both fibre-rich feeds while lupine had the largest influence on "boar" taint reduction in female pigs. PMID- 22063853 TI - Effect of high pressure treatment on colour, microbial and chemical characteristics of dry cured loin. AB - The effect of high pressure on sliced and vacuum packaged commercial dry-cured pork loin was determined by analysing the induced colour changes, the residual enzymatic activities of cathepsins, aminopeptidases and dipeptidilpeptidases and the changes in the content of free amino acids and also its effect on lipid oxidation, as TBARS (Thiobarbituric reactives substances) and volatile flavour compounds. High pressure treatments above 300MPa affected the colour of dry cured pork loins producing an increase in lightness and decreased redness and these differences were detected during all vacuum storage. High pressure produced a reduction in the activity of aminopeptidases and dipeptidylpeptidases. The untreated samples showed an increase in free amino acid content during vacuum storage while the pressurised samples showed no significant increases probably due to the reduction in aminopeptidase activity. The oxidative stability of the pressurised dry-cured loins was not affected as observed by the absence of differences in TBARS values and in the abundance of volatile compounds from the lipid oxidation. However, the pressurised treatment produced a reduction of several flavour compounds, particularly those derived from Maillard reactions, although they are regenerated during vacuum storage. In summary, high pressure treatment after the ripening of dry-cured loin affects its quality but the differences can be minimised by vacuum storage. PMID- 22063854 TI - Effect of the packaging method and the storage time on lipid oxidation and colour stability on dry fermented sausage salchichon manufactured with raw material with a high level of mono and polyunsaturated fatty acids. AB - The effects of fatty acid composition, two packaging methods (vacuum and 20% CO(2)/80% N(2)) and storage under refrigeration for 210 days were evaluated on a dry fermented sausage (salchichon), manufactured with raw material enriched in monounsaturated or polyunsaturated fatty acids. Fatty acid composition was determined on sausage mixtures and on ripened sausages and lipid oxidation and colour stability was determined on ripened sausage at different times during storage. The modification of fatty acid composition of the sausages raised the nutritional quality, slightly affecting the colour properties. Dry fermented sausages enriched in polyunsaturated and monounsaturated fatty acids presented higher lipid oxidation values than the control ones. Both packaging methods (vacuum and 20% CO(2)/80% N(2)) during 210 days of chilled storage had minor effects on the colour and the lipid oxidation stability. PMID- 22063855 TI - Effects of rapid chilling of carcasses and time of deboning on weight loss and technological quality of pork semimembranosus muscle. AB - The effect of rapid air chilling of carcasses in the first 3 h of chilling at -31 degrees C (then at 2-4 degrees C, till 24 h post-mortem) and the possibility of earlier deboning (8 h post-mortem) after rapid air chilling, compared to conventional air chilling (at 2-4 degrees C, till 24 h post-mortem) on weight loss and technological quality (pH value, tenderness, drip loss, cooking loss and colour - L(*)a(*)b(*) values) of pork M. semimembranosus was investigated. Under the rapid chilling conditions, weight loss was 0.8% at 8 h post-mortem and increased to 1.4% at 24 h post-mortem when weight loss was 2.0% under conventional chilling. Carcasses that were rapid chilled had significantly lower (P<0.001) internal temperature in the deep leg at 4 (25.7 degrees C), 6 (13.0 degrees C), 8 (6.2 degrees C) and 24 h (3.8 degrees C) post-mortem compared to conventional chill treatment (32.7, 24.2, 19.1 and 5.1 degrees C, respectively). Rapid chilling reduced significantly (P<0.05) the rate of pH value decline at 8 h (6.02) post-mortem in M. semimembranosus compared to conventional chill treatment (5.88). Compared to conventional chilling, in M. semimembranosus deboned in different time post-mortem, rapid chilling had a positive significant effect on drip loss (P<0.05, muscles deboned 8 h post-mortem), cooking loss (P<0.001) and incidence of pale colour (L(*) value). Rapid chilling i.e. rapid chilling and earlier deboning had neither positive nor negative significant effects (P>0.05) on other investigated technological quality parameters of M. semimembranosus (tenderness, a(*) value and b(*) value) compared to conventional chilling. PMID- 22063856 TI - Development and quality evaluation of cooked buffalo tripe rolls. AB - Cooked buffalo tripe rolls (BTRs) were prepared from a combination of buffalo tripe (75%) and buffalo meat (25%) by using mincing (M-BTR) and blade tenderization (BT-BTR). They were stored at 4+/-1 degrees C and studied for various physico-chemical, sensory and microbial qualities. Significantly (P<0.01) higher pH, shear force value, diameter shrinkage and fat percentage were observed in M-BTR and BT-BTR than control product (100% minced buffalo meat). The product yield and drip loss percentage were significantly (P<0.01) lower in BT-BTR, whereas drip loss percentage was significantly higher in M-BTR compared to controls and BT-BTR. No significant change was noticed in protein and moisture content between the different products. All physico-chemical parameters and sensory evaluation scores of M-BTR were comparable with control. Significant (P<0.01) increases were noticed in pH, moisture content, thiobarbituric acid and tyrosine values with increasing storage period, whereas the extract release volume decreased significantly. All microbial counts and sensory evaluation scores were within the acceptable limits until 15 days of storage at 4+/-1 degrees C in low-density polyethylene pouches stored aerobically. PMID- 22063857 TI - Carcass and meat quality traits of wild boar (Sus scrofas. L.) with 2n=36 karyotype compared to those of phenotypically similar crossbreeds (2n=37 and 2n=38) raised under same farming conditions. 1. Carcass quantity and meat dressing. AB - The aim of this study was to compare wild boar (chromosomal number 2n=36) to phenotypically similar animals of 2n=37 and 2n=38 chromosomes (crossbreeds) with respect to live weight, carcass yield, meat yield, fat and weight of inner organs. All animals were born and raised on the same farm and slaughtered at 39 weeks. The final live weight of wild boar 2n=36 was significantly lower (47.2kg) as compared to crossbreeds (80.0kg). Animals 2n=36 had more carcass yields (65.5%) than 2n=37 karyotype (64.9%) and 2n=38 (64.4%). Wild boar had the highest yields for the cuts with bones and boneless cuts compared to crossbreeds. Therefore, variations in karyotype are accompanied by differences in some carcass quantitative traits, i.e., 2n=36 grow and fatten slower than crossbreeds 2n=37 and 2n=38. PMID- 22063858 TI - Preliminary investigations on the effects of ageing and cooking on the Raman spectra of porcine longissimus dorsi. AB - The influence of ageing and cooking on the Raman spectrum of porcine longissimus dorsi was investigated. The rich information contained in the Raman spectrum was highlighted, with numerous changes attributed to changes in the environment and conformations of the myofibrillar proteins. Predictions equations for shear force and cooking loss were developed from the Raman spectra of both raw and cooked pork. Good correlations and standard errors of prediction were obtained for both WB shear force and cooking loss, with the raw and the cooked samples showing almost identical results R(2)=0.77, root mean standard error of prediction (RMSEP)% of mean=12% for shear force; R(2)=0.71, RMSEP% of mean=10% for cooking loss. The Raman spectra were also able to predict the extent of cooking that occurred within the pork (R(2)(val)=0.94, RMSEP% of range=5.5%). Raman spectroscopy has considerable potential as a method for non-destructive and rapid determination of pork quality parameters such as tenderness. Raman spectroscopy may provide a means of determining changes during cooking and the extent to which foods have been cooked. PMID- 22063859 TI - Traceability of four European Protected Geographic Indication (PGI) beef products using Single Nucleotide Polymorphisms (SNP) and Bayesian statistics. AB - The use of SNPs in combination with Bayesian statistics for the geographic traceability of cattle was evaluated using a dataset comprising 24 breeds from Italy, France, Spain, Denmark, the Netherlands, Switzerland and UK genotyped with 90 polymorphic markers. The percentage of correct assignment of the individuals to their Country of origin was 90%, with an average assignment probability of 93% and an average specificity of 92%. The higher value was observed for UK breeds (97% of correct assignment) while Swiss animals were the most difficult to allocate (77% of correct assignment). Tracing of Protected Geographic Indication (PGI) products, the approach correctly assigned 100% of Guaranteed Pure Highland Beef; 97% of "Vitellone dell'Appennino Centrale" breeds; 84% of Ternera de Navarra, and 80% of Boeuf de Chalosse. Methods to verify Products of Designated Origin (PDO) and Protected Geographic Indication (PGI) products will help to protect regional foods and promote the economic growth of marginal rural areas by encouraging the production of high quality niche market foods. PMID- 22063860 TI - Effect of ractopamine level, gender, and duration of ractopamine on belly and bacon quality traits. AB - The objective was to determine belly and bacon quality traits in pigs fed ractopamine (RAC) for various durations during finishing. A 2*3*2 factorial arrangement was used with barrows and gilts, fed RAC levels of 0.0, 5.0, or 7.4ppm, for 21 or 28d prior to harvest. Bellies were fabricated and measured for length, thickness, firmness, and processing yields. Once processed, 1.27cm slices were removed at 25%, 50%, and 75% the distance from the blade end, packaged and digitally imaged using a Chem1 Genius(2) Bio Imaging System. Total slice area (TA), total slice length (TL), secondary lean length (SL), secondary lean area (SA), and percent lean area (TA - all lean components=LA) were determined by tracing images in Adobe Photoshop Elements. A composite sample from the three slices was used for proximate analysis to determine moisture and fat composition for each belly. Feeding RAC increased belly yield, TA, TL, SA, and LA (P<0.05), but did not alter moisture or fat composition (P>0.05). Gilts had decreased firmness and higher pump uptakes compared to barrows (P<0.05). Additionally gilts had increased TL, SL, and LA with lower fat and higher moisture content (P<0.05). RAC feeding duration had no significant effect on belly or bacon quality traits (P>0.05), furthermore, no interactions were found to be significant (P>0.05). RAC administration during finishing resulted in improved belly and bacon yields with no negative effects on the quality traits evaluated. PMID- 22063861 TI - Quality of donkey meat and carcass characteristics. AB - A study based on 15 entire donkey males was carried out to evaluate carcass quality and nutritional characteristics of meat obtained by these animals slaughtered at 15 months of age and a mean final body weight of 181kg. The meat had a low (2.02g/100g) fat content, an appreciable (22.8g/100g) protein content, and cholesterol content was 68.7mg/100g. Glycogen was also determined (0.45g/100g) within 12h of sampling. Potassium was the mineral with the highest content (343mg/100g), followed by phosphorus (212mg/100g), sodium (52mg/100g) and magnesium (24mg/100g). Donkey meat obtained from young animals can be considered a good alternative to other red meats and not only for the production salami, or other fermented meat products. PMID- 22063862 TI - Sensory characterisation and consumer acceptability of small calibre fermented sausages with 50% substitution of NaCl by mixtures of KCl and potassium lactate. AB - The effect of six mixtures with 50% molar substitution of KCl (0-50%) and potassium lactate (0-50%) as NaCl substitutes in small calibre fermented sausages on some sensory parameters and on the acceptability was studied. Also, the relationship between sensory profile and consumer acceptability using external preference mapping was investigated. The results showed that as the K-lactate substitution increased, pH, sweetness, crumbliness and pastiness also increased, and piquantness, hardness, cohesiveness, ripened flavour, acid taste and saltiness decreased. However, the treatments prepared with a high level of salt substitution by KCl showed scores of sensory attributes similar to those of the control. Consumer segmentation showed differences in acceptability between genders, place of residence, educational level and age group. Consumers rejected fermented sausages with high K-lactate substitution but not those with a high KCl substitution. External preference mapping split consumers up into four clusters with different preference patterns. According to these results and from a sensory point of view, it is possible to achieve a reduction of 50% of NaCl in small calibre fermented sausages and to obtain a product acceptable to most consumers. PMID- 22063863 TI - Development of a hybrid image processing algorithm for automatic evaluation of intramuscular fat content in beef M. longissimus dorsi. AB - An automatic method for estimating the content of intramuscular fat (IMF) in beef M. longissimus dorsi (LD) was developed using a sequence of image processing algorithm. To extract IMF particles within the LD muscle from structural features of intermuscular fat surrounding the muscle, three steps of image processing algorithm were developed, i.e. bilateral filter for noise removal, kernel fuzzy c means clustering (KFCM) for segmentation, and vector confidence connected and flood fill for IMF extraction. The technique of bilateral filtering was firstly applied to reduce the noise and enhance the contrast of the beef image. KFCM was then used to segment the filtered beef image into lean, fat, and background. The IMF was finally extracted from the original beef image by using the techniques of vector confidence connected and flood filling. The performance of the algorithm developed was verified by correlation analysis between the IMF characteristics and the percentage of chemically extractable IMF content (P<0.05). Five IMF features are very significantly correlated with the fat content (P<0.001), including count densities of middle (CDMiddle) and large (CDLarge) fat particles, area densities of middle and large fat particles, and total fat area per unit LD area. The highest coefficient is 0.852 for CDLarge. PMID- 22063864 TI - Molecular and technological characterization of lactic acid bacteria from traditional fermented sausages of Basilicata region (Southern Italy). AB - Lactic acid bacteria (LAB) from traditional fermented sausages of the Basilicata region were investigated by ARDRA-PCR and RAPD-PCR for taxonomic identification at species and strain level and characterized on the basis of the growth and acidification at different temperatures, incubation times, levels of NaCl and KNO(2), hydrolysis of sarcoplasmatic and myofibrillar proteins and antimicrobial, peptide/amino acid release and nitrate reductase activities. Lactobacillus sakei was the predominant species (67%) followed by Pediococcus pentosaceus (16%), Leuconostoc carnosum (8%), Lactobacillus plantarum (4%), Lactobacillus brevis (2%) and Leuconostoc pseudomesenteroides (2%). The technological characterization revealed that most of the isolates had good acidifying and proteolytic properties. Moreover, Lb. sakei strains showed antimicrobial ability, while Leuconostoc strains the highest reduction of nitrates. This work was a preliminary study in the formulation of autochthonous starter cultures in order to standardize the production process of sausages, to preserve their typical organoleptic and sensory characteristics and to improve the quality of final product. PMID- 22063865 TI - Southern Spain lamb types discrimination by using visible spectroscopy and basic physicochemical traits. AB - The potential for using visible spectroscopy (400-700nm) to classify six types (breed*production system) of lamb meat was investigated. Seven wavelengths namely 400, 410, 420, 450, 510, 610 and 670nm were retained for the discriminant analysis. The basic meat physicochemical traits of Longissimus dorsi were also studied and a model including that information together with the spectra was developed to compare both accuracies. Then, Myoglobin content, water holding capacity, pH, a(*), 670 and 610nm wavelengths, protein percentage, L(*), ash content, 450 and 420nm wavelengths and moisture percentage were selected as variables for the development of the discriminant function. The data analysis showed that it was possible to discriminate the lamb types with accuracy around 83% using visible spectroscopy. However these results improved to 95% when using the reflectance together with basic physicochemical traits (12% better than using only the spectra). PMID- 22063866 TI - Monitoring of warmed-over flavour in pork using the electronic nose - correlation to sensory attributes and secondary lipid oxidation products. AB - Sensory analysis of meatballs was carried out to monitor the warmed-over flavour (WOF) development in cooked, cold-stored (at 4 degrees C for 0, 2 and 4days) and reheated meatballs derived from M. longissimus dorsi (LD) and M. semimembranosus (SM) of pigs fed a standard diet supplemented with either 3% of rapeseed oil or 3% of palm oil. This was performed in combination with measurement of volatile compounds using a solid-state-based gas sensor array system (electronic nose) and gas chromatography/mass spectrometry together with measurement of thiobarbitoric acid reactive substances (TBARS). Subsequently, to elucidate the relations and predictability between the obtained data, the gas sensor responses were correlated with chemical (volatile and non-volatile secondary lipid oxidation products) and sensory data (flavour and odour attributes), using partial least squares regression modelling (PLSR). The TBARS, hexanal, pentanal, pentanol and nonanal all correlated to the sensory attributes associated to WOF formation. Moreover, the responses from eight of the MOS (metal oxide semiconductor) sensors within the electronic nose proved to be significantly related to WOF characteristics detected by both sensory and chemical analysis, while six of the MOSFET (metal oxide semiconductor field effect transistor) sensors were related to freshly cooked meat attributes determined by sensory analysis. The obtained results show the potential of the present gas sensor technology to monitor WOF formation in pork. PMID- 22063867 TI - Marinating as a technology to shift sensory thresholds in ready-to-eat entire male pork meat. AB - This study investigated the effect of marinades in improving the eating quality in ready-to-eat boar meat. Neck chops with fat content below 18.9%, skatole ?1.1ppm (range 0.03-1.1) and androstenone ?5.6ppm (range 0.01-5.6) were used. In a screening experiment different marinades were tested for their ability to mask boar taint (defined as manure and urine odour and flavour). Liquid smoke and oregano extracts appeared to have the best potential for masking, and were studied in detail. Results from the study indicated that marinated chops with skatole content of approximately 0.4ppm appeared similar to castrates in boar taint. Chops with skatole contents above 0.7ppm remained unmasked despite the use of strongly flavoured marinades. Unmarinated chops served at 60 degrees C were more tainted than those served at 15 degrees C, but scored lower for boar taint when reheated, although the concentrations of androstenone and skatole remained the same. The fat content of the chops was not well correlated to the perception of boar taint. The attributes manure and urine were correlated with the level of skatole, but urine attribute was not a good indicator of the androstenone level. PMID- 22063868 TI - Prediction of beef eating quality from colour, marbling and wavelet texture features. AB - Beef longissimus dorsi colour, marbling fat and surface texture are long established properties that are used in some countries by expert graders to classify beef carcasses, with subjective and inconsistent decision. As a computer vision system can deliver objective and consistent decisions rapidly and is capable of handling a greater variety of image features, attempts have been made to develop computerised predictions of eating quality based on these and other properties but have failed to adequately model the variation in eating quality. Therefore, in this study, examination of the ribeye at high magnification and consideration of a broad range of colour and marbling fat features was used to attempt to provide better information on beef eating quality. Wavelets were used to describe the image texture of the beef surface at high magnification rather than classical methods such as run lengths, difference histograms and co occurrence matrices. Sensory panel and Instron analyses were performed on duplicate steaks to measure the quality of the beef. Using the classical statistical method of partial least squares regression (PLSR) it was possible to model a very high proportion of the variation in eating quality (r(2)=0.88 for sensory overall acceptability and r(2)=0.85 for 7-day WBS). Addition of non linear texture terms to the models gave some improvements. PMID- 22063869 TI - Factors that affect and motivate the purchase of quality-labelled beef in Spain. AB - The aim of the present study was to identify the factors that affect and motivate the purchase of quality-labelled beef in Spain. For this purpose a total of 364 surveys were carried out on buyers of beef in three Spanish cities. The sample was divided into three groups of buyers according to the frequency with which they buy beef with a quality label. A logistic regression analysis was used to estimate the differences between groups. The results showed the importance of the production region as a quality aspect. In general terms, variables such as income level and lifestyles would seem to be the variables that enable us to discriminate between quality-labelled beef buyers and non-buyers, whereas beef purchasing habits, a greater appreciation of production systems and attitudes towards quality-labelled beef, are the variables that may explain the differences that exist between regular and occasional quality-labelled beef buyers. PMID- 22063870 TI - Fluorescence spectroscopy as a novel approach for the assessment of myofibrillar protein oxidation in oil-in-water emulsions. AB - The oxidation of oil-in-water emulsions (37 degrees C/10 days) containing increasing levels of myofibrillar proteins (MP) (0.5%, 1% and 2% on the basis of lipid content) was investigated. Protein oxidation was assessed by measuring the loss of natural tryptophan fluorescence and the increase in fluorescent protein oxidation products (FP) using fluorescence spectroscopy. Lipid oxidation was simultaneously analysed by measuring the increase of conjugated dienes (CD) and hexanal. The oxidative degradation of tryptophan residues occurred as an early event in MP oxidation whereas FP formed later as secondary protein oxidation products. The shift of the tryptophan maximum fluorescence emission wavelength during oxidation provided information about the location of oxidising tryptophan residues. Emulsions with higher concentrations of MP displayed higher tryptophan fluorescence and yielded a higher amount of FP. MP acted as inhibitors of lipid oxidation because emulsions with higher MP contents contained lower levels of CD and hexanal. Significant negative correlations were found between tryptophan fluorescence and CD, reflecting the timely interaction between primary lipid oxidation products and protein oxidation. Both spectrophotometric techniques were useful although the loss of tryptophan fluorescence is more reliable since it is a specific measurement which is not affected by the presence of other fluorescent protein oxidation products. PMID- 22063871 TI - Simulation of giant fibre development in biopsy samples from pig longissimus muscle. AB - The incidence of hyper-contracted giant fibres in pig postmortem skeletal muscle is closely related to poor meat quality in terms of pale, soft, and exudative pork. Detection of a predisposition to develop giant fibres in live pigs could help to predict pork quality and to exclude affected pigs from genetic selection. The abundance and proportion of giant fibres in longissimus muscle were highest in Pietrain followed by Landrace, Large White, and Leicoma pigs of market weight. The postmortem development of giant fibres could be successfully simulated in vitro incubating biopsy samples from longissimus muscle at 37 degrees C for 60min. For repeated measurements on three samples the intraclass correlation coefficient for the number of giant fibres/cm(2) was theta^(3)=0.69 for biopsy and theta^(3)=0.87 for carcass samples. "Simulated" giant fibres exhibited ultrastructural changes in plasma membrane, myofibrils, mitochondria, and sarcoplasmatic reticulum as shown previously for giant fibres in carcass samples. PMID- 22063872 TI - Comparative efficacy of pomegranate juice, pomegranate rind powder extract and BHT as antioxidants in cooked chicken patties. AB - A study was carried out to evaluate the antioxidant potential of pomegranate juice (PJ), rind powder extract (RP) and butylated hydroxyl toluene (BHT) in cooked chicken patties during refrigerated storage. Freshly minced chicken meats were assigned to one of the following four treatments: control (meat treated with no antioxidants); 10mg equivalent PJ phenolics per 100g meat; 10mg equivalent RP phenolics per 100g meat; 10mg BHT per 100g meat. The patties formed from the minced meats were grilled for 20min and stored under aerobically at 4 degrees C for 15 days. Total phenolic content (as tannic acid equivalent) significantly (P<0.05) increased from 152 in control to 195 and 224MUg/g in PJ and RP patties. Addition of PJ or RP did not affect any of the sensory attributes. The TBARS values were significantly (P<0.05) reduced from 1.272 in control patties to 0.896, 0.763 and 0.203mg malonaldehyde per kg samples in BHT, PJ and RP patties, respectively. The RP treatment substantially inhibited (P<0.01) lipid oxidation in cooked chicken patties to a much greater extent than BHT treatment. The PJ or RP at a level of 10mg equivalent phenolics/100g meat would be sufficient to protect chicken patties against oxidative rancidity for periods longer than the most commonly used synthetic antioxidant like BHT. PMID- 22063873 TI - Effect of dietary conjugated linoleic acid in combination with monounsaturated fatty acids on the meat composition and quality traits of dry-cured loin. AB - Three levels (0%, 1% and 2%) of an enriched conjugated linoleic acid oil (CLA) were combined with two levels of monounsaturated fatty acids (MUFA) (low -19% average and high -39% average) for pig feeding. Composition, weight losses, lipid oxidation (thiobarbituric acid test, TBARs), change in the fatty acid content of the lipid fractions and sensory analysis of dry-cured loin as affected by dietary CLA, MUFA and CLA*MUFA interaction were studied. CLA and CLA*MUFA did not affect moisture and intramuscular fat content of dry-cured loin, weight losses during the processing, changes in the content of most fatty acids from lipid fractions and sensory traits. CLA and MUFA supplementation led to lower TBARs values (1.3mg MDA/kg sample for 0% CLA and 0.9mg MDA/kg sample for 2% CLA; 1.2mg MDA/kg sample for low MUFA diets and 0.9mg MDA/kg sample for high MUFA diets), the highest TBARs values being detected for 0% CLA-low MUFA diets [1.5mg MDA/kg sample]. The combination of dietary CLA with different MUFA levels in pig diets did not affect most composition and quality traits of dry-cured loin. Dietary CLA and MUFA seemed to lead to lower lipid oxidation in this product. PMID- 22063874 TI - Fluorimetric detection of protoporphyrins as an indicator for quality monitoring of fresh intact pork meat. AB - In fresh meat production fast and non-destructive quality monitoring along the distribution chain is a key aspect to guaranteeing high quality and safe products for consumption. The applicability of fluorescence spectroscopy using protoporphyrins as indicators for meat ageing was investigated. Porcine musculus longissimus dorsi (MLD) was stored in slices over 20 days at 5 and 12 degrees C and measured every day with an excitation of 420nm and an emission range of 550 750nm. Additionally, pH, drip loss and colour were examined to assess possible correlations. The obtained spectra of the MLD showed an increase in three peaks at 592, 638 and 705nm which could be reconstructed using the spectra of standard solutions of protoporphyrin IX (PP) and zinc protoporphyrin IX (ZnPP) or magnesium protoporphyrin (MgPP), respectively. Using principal component analysis (PCA) on the fluorescence spectral data, the meat slices stored at 5 degrees C showed differences in the fluorescence signal after the 10th day and 5th day when stored at 12 degrees C. An interrelationship between the additional analyses and the fluorescence intensities on these relevant days could not be established. In conclusion, the increase of ZnPP fluorescence due to temperature related changes of physiological meat properties is capable of serving as a quality indicator with regards to inadequate conditioning (e.g. during transportation and/or storage) of pork meat. PMID- 22063875 TI - Inhibition of lipid oxidation in refrigerated and frozen salted raw minced chicken breasts with electron beam irradiated almond skin powder. AB - Antioxidant effects of electron beam irradiated almond skin powder (ASP) in raw minced chicken breasts (MCB) during refrigerated and frozen storage were studied. MCB samples were treated with BHT, non-irradiated ASP (0kGy), irradiated ASP (10kGy, 20kGy and 30kGy) and compared to MCB without antioxidants. Colour was determined on initial and final day of analysis while conjugated dienes (CD), peroxide values (POV), TBARS and hexanal content were evaluated periodically for 12 days of refrigerated storage and seven months of frozen storage. ASP addition lowered L* values compared to MCB without ASP or BHT. During refrigerated storage, MCB containing ASP had decreased formation of lipid oxidation products ranging from 0 to 66%, 7 to 24%, 0 to 37% and 4 to 71% reduction in POV, CD, TBARS and hexanal content, respectively, as compared to MCB without antioxidants over duration of study. A 15-65%, 3-25%, 14-50% and 28-82% reduction in POV, CD, TBARS and hexanal content, respectively, for frozen MCB was detected. PMID- 22063876 TI - Effect of a 10-day ageing at 30 degrees C on the texture of dry-cured hams processed at temperatures up to 18 degrees C in relation to raw meat pH and salting time. AB - The aim of this study was to investigate the effect of a 10-day ageing at 30+/-2 degrees C on the texture of dry-cured hams processed at temperatures up to 18+/-2 degrees C for 12 months in relation with raw ham pH and salting time. Three pH groups (semimembranosus muscle at 24h post-mortem: Low pH<5.7, Medium pH=5.7?pH?5.9, and High pH>5.9), three salting times (6d, 10d and 14d) and two ageing temperatures (18 degrees C and 30 degrees C) were investigated. Physicochemical characteristics, instrumental and sensory texture and product sliceability were evaluated on biceps femoris and semimembranosus muscles. Hams with pH(SM24)<5.7 should be avoided in order to reduce the incidence of texture problems in dry-cured ham elaboration. Texture problems are especially important in hams with a reduced salt content that are mechanically sliced (not frozen). A 10-day ageing at 30 degrees C could be useful for reducing the soft texture problems in dry-cured hams processed at temperatures up to 18 degrees C for 12 months without affecting the product flavour. PMID- 22063877 TI - The application of wheat fibre and soy isolate impregnated with iodine salts to fortify processed meats. AB - The aim was to use wheat dietary fibre and soy protein isolate as carriers of KI and KIO(3) for fortification of processed meat with iodine. Products from minced pork were prepared with addition of iodised wheat fibre and soy isolate, and iodised table salt for comparison and the effects of thermal processing and storage on changes in iodine content were determined. It was shown that both alternative carriers limited the iodine changes in meat products compared with iodised table salt. However, wheat fibre was more effective in limiting iodine losses during thermal processing and soy protein during storage of the products. The greatest effect of the carriers was found in meat products fortified with the less stable KI. PMID- 22063878 TI - Evaluation of post mortem stability of porcine skeletal muscle RNA. AB - The objective of this study was to evaluate the effect of postmortem times on the quality of porcine skeletal muscle total RNA in order to consider the possibility to use postmortem material for gene expression analysis. Samples of Musculus semimembranosus were collected at 20min, 2h, 6h, 24h and 48h postmortem from the left legs of four commercial heavy pigs. Total RNA was analysed by agarose gel electrophoresis stained with ethidium bromide and by microfluidic capillary electrophoresis on an Agilent 2100 Bioanalyzer instrument obtaining 28S:18S rRNA peak ratios and RIN values. The average RIN values of the analysed samples were 7.45+/-0.13, 7.43+/-0.15, 7.45+/-0.10, 7.33+/-0.15 and 3.95+/-0.58 for the same postmortem times, respectively, indicating that RNA degradation was present at 48h postmortem. In a similar experiment, carried out by other authors on beef cattle muscle total RNA extracted at different postmortem times, RNA was stable up to 8days after death as indicated by intact 28S and 18S rRNA bands. Thus, differences among species or other environmental factors might affect the level of RNA degradation. In the porcine postmortem samples, qualitative assessment of GAPDH transcripts by PCR amplification of different cDNA fragments indicated that postmortem stages did not affect the possibility of analysing this housekeeping gene. Thus, postmortem porcine skeletal muscle can be an useful tissue to obtain gene expression based information. PMID- 22063879 TI - Growth inhibition of bacterial isolates recovered from two types of Portuguese dry smoked sausages (chourico). AB - Potassium sorbate (PS), sodium benzoate (SB) and methyl p-hydroxybenzoate (MHB) were investigated as surface treatments for their ability to inhibit the growth of 18 isolates of spoilage and pathogenic bacteria from two types of Portuguese dry smoked sausages (Chourico). MHB significantly inhibited the growth rate of 12 of the isolates (p<0.05) whereas no effect was observed for four isolates of lactic acid bacteria, identified as Enterococcusfaecium, Pediococcusacidilactici and Lactobacilluscurvatus, and two isolates identified as Clostridiumaminovalericum and Staphylococcusepidermidis. PS and SB had less influence on the bacterial growth rates. It was concluded that MHB can be applied as surface treatment to improve the stability and safety of the product along shelf life period in modified atmosphere package. PMID- 22063880 TI - Antigen-specific IFN-gamma and IL-4 production in caprine herpesvirus infected goats. AB - The analysis of cytokines secreted by antigen-specific lymphocytes is hampered in goats by the paucity of species-specific reagents yet it is crucial to study immune responses to infections. To overcome this limit, two commercial kits designed to measure soluble bovine IL-4 (by ELISA) and frequencies of bovine IFN gamma secreting cells (by ELISPOT) were tested for cross-reactivity in goats. In addition, an ELISA specific to bovine/ovine IL-4 and employing two monoclonal antibodies, clones CC313 and CC314, was tested as well. Concanavalin A-stimulated caprine peripheral blood mononuclear cells (PBMCs) cultures were studied and they exhibited high levels of soluble IL-4 and high frequencies of IFN-gamma secreting cells. In addition, the two IL-4 ELISAs detected similar amounts of cytokine. To start defining the cytokine response triggered by caprine herpesvirus 1 (CpHV-1) infection, PBMC cultures were setup from goats naturally or experimentally infected with CpHV-1. High frequencies of IFN-gamma producing cells and low, when detectable, levels of soluble IL-4 were observed in CpHV-1-specific PBMC cultures from both groups of infected goats. Thus, the availability of cross-reactive research tools can expand cytokine studies in goats and can implement the research on immunity to other caprine infections. PMID- 22063881 TI - Determination of the lean meat percentage of pig carcasses using magnetic resonance imaging. AB - The purpose of Workpackage 3 of the European Eupigclass project was to test indirect methods of measuring the lean meat percentage of a carcass that would be less costly, at least as accurate and more consistent than dissection. Magnetic resonance imaging was one of the three indirect methods tested to measure the lean meat weight and the lean meat percentage of pig carcasses, the other methods being X-ray CT and vision techniques. One hundred and twenty carcasses from three different genotypes and from both sexes were slaughtered. The left parts of the carcasses were fully dissected and the right parts were investigated with an indirect method using a 1.5T MRI system. The acquisition protocol was chosen to give an optimized contrast between fat and muscle tissues. Two different approaches, image segmentation and PLS regression, were used to extract information from the images. Automatic image segmentation was performed to quantify the volume of muscle in the images and gave a standard error of prediction using a linear regression with the dissection of the left half carcasses of 586g and 1.10% for lean meat weight and lean meat percentage, respectively. PLS regression using the signal intensities histograms gave an estimation error of 465g for lean meat weight. These results showed that MRI could be used in place of full dissection for authorizing and monitoring classification equipment of pig carcasses. PMID- 22063882 TI - Influence of maternal feed rationing on metabolic and contractile properties of Longissimus lumborum muscle fibres in the rabbit offspring. AB - Thirty hybrid female rabbits of 15 weeks of age were divided into three groups and fed for 8 weeks (until the first parturition) on one of the three following diets: "C diet" (DE=11.71MJ/kg DM) fed ad libitum; "R diet" was the C diet fed at 80% of ad libitum, "F diet" rich in fibre (24.6% vs 18.7% for C diet; DE=9.77MJ/kg DM) fed ad libitum. Afterwards, all the does received the C diet ad libitum. One pup per litter was slaughtered at birth, one at 35d (weaning) and one at 81d of age. At the second parturition, another pup per litter was slaughtered at birth. Ten minutes post mortem the Longissimus lumborum (LL) muscle was sampled and the mean cross-sectional area, compactness index (CI) and sphericity of the fibres of the new-born rabbits were determined; on rabbits of 35 and 81d of age the fibre type distribution (betaR, alphaR or alphaW) was also measured. The two maternal rationed-diets significantly increased the CI of LL fibres of new-born rabbits of the first kindling, compared to the C diet. On weaning rabbits the greatest effect of maternal feed rationing was observed on the percentage of alphaW fibres (P<0.01), which was the highest for the F diet (85.2%), intermediate for the C diet (78.0%) and the lowest for the R diet (71.8%). At 81d of age, no effect of maternal dietary treatment was found on offspring. PMID- 22063883 TI - Relationship between water content, NaCl content, pH and texture parameters in dry-cured muscles. AB - The aim of the present study was to describe the effect of NaCl and pH on the relationship between water content and hardness, cohesiveness and springiness in dry-cured muscles. The experiment was undertaken using 18 hams, selected in a commercial slaughterhouse. Half of the hams had a pH<5.7 and the rest a pH>6.2, measured on the semimembranosus muscle at 24-h postmortem. The semimembranosus and biceps femoris muscles were cut from hams, cured and individually packaged in bags and were laid in trays in a room at 2+/-2 degrees C for 45days. Thereafter nine samples from each muscle were shaped like a parallelepiped and dried until different levels of drying, ranging from 28.5% to 59.7% water content, were attained. The rest of the muscle was ground and packaged until its subsequent physicochemical analysis. At the end of the drying period, a Texture Profile Analysis was used to determine textural parameters. The results indicated that for a range of X (kg H(2)O/kg dry matter) between 0.8 and 1.3 the hardness remains practically unchanged while for X<0.6 the hardness increases substantially. The samples from hams with low pH(SM) had greater hardness, cohesiveness and springiness than those from hams with high pH(SM). Dry-cured muscles with lower NaCl content showed lower hardness, cohesiveness and springiness, especially in those with pH(SM)>6.2. At X values lower than 0.6 the hardness was more influenced by water content than by NaCl content or pH(SM). PMID- 22063884 TI - The effect of production system and age on levels of iron, taurine, carnosine, coenzyme Q(10), and creatine in beef muscles and liver. AB - Samples of longissimus (LL) and triceps brachii (TB) muscles from Angus-cross heifers finished either on a high-concentrate ration in Washington, USA, (US cattle, n=15) or on pasture in New Zealand (NZ cattle, n=16) were assessed for composition characteristics. Half of the NZ cattle were of a similar age to the US cattle (NZAge) and half were of a similar weight (NZWt). Iron concentration was higher in TB (20.9 vs. 17.5MUgg(-1); P<0.001) and was higher for the NZWt group than the NZAge group or the US cattle. The proportion of iron as haem iron was highest for the NZWt group (87.3%; P<0.01), but the proportion as soluble haem iron was highest for the US cattle. For a sub-group of 10 pasture-finished cattle, iron levels in cheek muscle were higher than for LL or TB, and liver levels were 66% higher than cheek muscle. The proportion of haem iron, however, was lowest in liver (55.3%) and was lower in cheek muscle (78.4%) than LL or TB. Relative to LL, TB had higher levels of taurine and coenzyme Q(10), but lower levels of carnosine, creatine and creatinine, as expected for a muscle with a more aerobic metabolism. These differences were magnified for the even more aerobic cheek muscle. Differences between the two NZ groups were small, but muscles from the US cattle contained less taurine, carnosine, coenzyme Q(10), and creatinine. Reasons for these differences in various meat components for similar cattle from different production systems are not clear. PMID- 22063885 TI - The effect of production system and age on concentrations of fatty acids in intramuscular fat of the longissimus and triceps brachii muscles of Angus-cross heifers. AB - The concentrations of fatty acids were measured in intramuscular fat from the longissimus lumborum (LL) and triceps brachii (TB) muscles of Angus-cross heifers finished either on a high-concentrate ration in Washington, USA, (US cattle, n=15) or on pasture in New Zealand (NZ cattle, n=16). Half of the NZ cattle were of a similar age to the US cattle (NZAge) and half were of a similar weight (NZWt). Intramuscular fat levels were higher for the LL muscle and for the US cattle but only within the LL muscle (P<0.05). Aspects of the fatty-acid patterns that are of relevance to human nutrition tended to favour the pasture-finished NZ cattle with lower n-6/n-3 fatty acid ratios (P<0.001), higher concentrations of an anticarcinogenic conjugated linoleic acid (C18:2 c9,t11) (P<0.05) and its precursor (trans-vaccenic acid, TVA) (P<0.01), and lower levels of the 18-carbon trans monounsaturated fatty acids other than TVA (P<0.01). Concentrations of 20 of the 22 fatty acids analysed differed significantly between the two muscles. When values were adjusted to a common intramuscular fat level by covariance, most of the group differences remained, but a number of the muscle differences became non-significant. For almost half the fatty acids considered, there was a significant interaction between treatment group and muscle, which indicates that the results for one muscle do not necessarily apply to other muscles, although the ranking of the groups was usually the same for both muscles. PMID- 22063886 TI - A method for simultaneous fluorometry and rheology of connective tissue in bulk meat. AB - A probe tipped with optical fibres was mounted on the load cell of a compression tester and pushed into well-aged beef rib roasts (Canada Grade AAA, n=6, 33+/ 3.6days post-mortem). Fluorescence (F; excitation 365nm, emission >420nm) and reflectance (R; 365nm) were measured through single optical fibres. Diffuse R was measured using different fibres for illumination and detection, thus responding to tissue between the two fibres. Replication was by a matrix pattern of penetrations on single roasts. For example, in a typical roast, F was correlated with the force of penetration (mean r=0.86+/-0.06, n=20, all P<0.001). R was less (P<0.001) strongly correlated with penetration force (mean r=0.46+/-0.10, n=20, all P<0.001). F signals from connective tissue contained less peaks than R signals from both connective and adipose tissue (respectively, 2.75+/-0.43 versus 5.57+/-0.67peakscm(-1), P<0.001, n=20 pairs) and F peaks were wider than R peaks (respectively, 3.54+/-0.88 versus 1.38+/-0.19mm, P<0.001, n=20 pairs). For the spinales dorsi aponeurosis, the depth at which peak force was reached was strongly correlated with the depths at which both peak F and peak R were reached (r=0.98, P<0.001, n=20 for both). Diffuse R was only weakly correlated with penetration force (mean r=0.29+/-0.12 with only 5/10 correlations significant P<0.001). This new method showed the primary resistance to dorso-ventral penetrometry of well-aged beef rib roasts originated from connective tissue. PMID- 22063887 TI - Effects of rice bran on sensory and physico-chemical properties of emulsified pork meatballs. AB - Four kinds of bran, which are milled from important rice cultivators in Taiwan, have high contents of dietary fiber, fat and protein. The use of rice bran in Kung-wan, an emulsified pork meatball, was investigated. It was found that protein and fat contents, and white index of meatballs decreased as the amount of bran increased. A texture profile analysis (TPA) also indicated the hardness, gumminess and chewiness of the Kung-wan decreased. The sensory scores of taste, texture and overall acceptability of meatballs with less than 10% added bran showed no significant difference from those for meatballs without bran. However, the added amount of 15% enriched meatballs resulted in inferior sensory scores. The bran's particle size profoundly affected the sensory and physico-chemical properties of the meat products. Meatballs enriched with smaller bran particles possessed higher TPA indices and sensory scores than those added with larger ones. No significant differences in proximate composition, cooking yield, color and sensory quality were found among emulsified meatballs enriched with four different kinds of bran. Conclusively, the suitable amount of rice bran that should be added to emulsified pork meatballs was less than 10% and a smaller particle size would result in better quality. PMID- 22063888 TI - Postmortem regulation of glycolysis by 6-phosphofructokinase in bovine M. Sternocephalicus pars mandibularis. AB - This experiment addressed the hypothesis that 6-phosphofructokinase (6-PFK) regulates glycolysis in postmortem in M. sternocephalicus pars mandibularis. In two separate experiments, muscle samples were excised from randomly-selected steers that would typically be found on a commercial slaughter floor. In the first experiment, two samples were obtained from each of 6 steers immediately post-exsanguination; one sample was immersed immediately in liquid nitrogen and the other was stored at 4 degrees C for 4 d, to compare 6-PFK enzyme activity and glycolytic intermediate concentrations between fresh and d 4 postmortem samples. The greatest activity of 6-PFK was measured in fresh muscle extracts at pH 7.4, whereas little activity was detectable at pH 7.0. 6-PFK activity measured at pH 7.4 in d 4 samples also was barely detectable. Hill coefficient values for 6-PFK in fresh samples measured at pH 7.4 or 7.0, and d 4 samples measured at pH 7.4 were 2.9, 0.8, and 0.7, respectively, indicating loss of cooperativity with both lowered pH during assay and with time postmortem. Glycogen concentrations decreased 45% from d 0 to d 4, to 39.6MUmol glycogen/g muscle. Muscle concentrations of free glucose increased (P<0.001) from 0.84MUmol/g at d 0 to 6.54MUmol/g at d 4. Fructose-6-phosphate and glucose-6-phosphate increased (P<0.001) from d 0 to d 4 (2.8-fold and 4.7-fold, respectively). Lactate began accumulating immediately (3.33MUmol/g) and was elevated to 45.9MUmol/g by d 4. In the second experiment, conversion of [U-(14)C]glucose to lactate, glycogen, and CO(2) was measured in vitro at pH 7.4 and 7.0 in fresh M. sternocephalicus pars mandibularis strips from four steers. Total [U-(14)C]glucose was less in muscle strips incubated at pH 7.0 than in those incubated at pH 7.4 (55.5 vs. 123nmol glucose utilized per 100mg muscle per h; P=0.04), due primarily to a reduction in glucose conversion to lactate. The conversion of glucose to glycogen or CO(2) in vitro was unaffected by media pH. These results suggest that the postmortem decline in pH in M. sternocephalicus pars mandibularis ultimately inactivates 6 PFK; this occurs prior to the depletion of glycogen reserves. PMID- 22063889 TI - Honey inhibits lipid oxidation in ready-to-eat ground beef patties. AB - Our objective was to evaluate the antioxidant capabilities of clover (CH) and wildflower honeys (WH) in delaying lipid oxidation in cooked and reheated ground beef patties stored in refrigerated and frozen states. CH and WH (5%, 10%, or 15% w/w) were each mixed separately into ground beef chuck (18% fat) and formed into 30g patties mixed with 1% salt (w/w). A control (CON) with no honey and a control with sodium tripolyphosphate (STP; 0.25% w/w) were used for comparison. Patties were cooked to 71 degrees C, overwrapped with oxygen-permeable PVC film and either stored refrigerated (4 degrees C) for 12 days or frozen (-18 degrees C) for 45 days. Cook yield, pH and water activity were measured on day 0. On designated sampling days, patties were reheated to 71 degrees C. Thiobarbituric acid-reactive substances (TBARS) and lipid hydroperoxides (LOOH) were measured spectrophotometrically to assess lipid oxidation. TBARS and LOOH of ready-to-eat (RTE) ground beef patties containing either CH or WH were lower (P<0.01) than CON patties following storage; however, STP patties had lower TBARS values than honey containing patties (P<0.01). WH and CH at 15% were equally effective in suppressing LOOH compared to STP in refrigerated and frozen patties. All honey concentrations improved cook yield, with 10% WH being more effective than STP. Both CH and WH delayed lipid oxidation in RTE ground beef patties stored at 4 degrees C and -18 degrees C, with WH decreasing LOOH formation in refrigerated patties as effectively as STP. Honey may be a natural alternative to phosphates to delay lipid oxidation. PMID- 22063890 TI - Meat color stability affected by barley variety fed in finishing diet to beef steers. AB - Angus crossbred steers were assigned randomly to one of four finishing diets based on corn, Chinook, Logan, or H3 barley. Steers were harvested and after a 72 h chill, carcass quality and yield grade data were collected. Beef ribs were removed from 72 carcasses for further analysis. Ribs were aged in vacuum bag at 2 degrees C for 14 days. After aging three adjacent steaks (3.18cm) were removed to determine color stability, tenderness, proximate analysis and pH. Diets fed to steers had no effect on quality and yield grade or tenderness of beef steaks. Steaks from steers fed Logan barley variety were significantly less red at 10 days of storage (Hunter a*=24.06) than steaks from steers fed the other barley varieties (Chinook a*=26.4; H3 a*=28.05) or corn (a*=26.14). Identification of barley varieties that affect color stability could result in designing diets specifically for improved color and increase the use of barley as a finishing grain. PMID- 22063891 TI - Effect of dietary supplementation of vitamin E on characteristics of lamb meat packed under modified atmosphere. AB - The effect of dietary vitamin E supplementation on modified-atmosphere packed lamb meat during storage was studied. Thirty-six weaned male Manchego breed lambs were fed diets supplemented with three different vitamin E concentrations (0, 250, 500 and 1000mg/kg feed) for an average of 37 days, in the 13-26kg live weight growth range. Slices of m. longissimus dorsi were packaged under modified atmosphere (70% O(2) and 30% CO(2)), stored at 2+/-1 degrees C in darkness for 14 and 28 days. Meat quality parameters after both storage periods were assessed. Dietary vitamin E supplementation significantly increased alpha-tocopherol concentration in muscle. Initially, lipid oxidation (TBARS), meat colour and bacterial load were similar in all groups. Lipid and colour oxidation of meat increased significantly (P<0.001) throughout storage. The increase was greater in non-supplemented lambs than in supplemented ones. The bacterial counts after 28 days of storage reached the limit for microbiological shelf life (7log(10)cfu/cm(2)). Dietary vitamin E supplementation increased the shelf life of meat packaged under modified atmosphere to 14 days. TBARS, pigment oxidation and bacterial load were inside the acceptable limit. The meat maintained its quality for 28 days of storage only when lambs were fed with the 1000mg/kg dietary supplement, though the bacterial load was at the limit of acceptability. PMID- 22063892 TI - Nutritional profile of restructured beef steak with added walnuts. AB - Amino acid, fatty acid profile, cholesterol, vitamin E and mineral contents were assessed in restructured beef steak with 20% added walnut (20W). Compared with control restructured beef steak (0% added walnut), the product with added walnut presented a lower (P<0.05) lysine/arginine ratio, larger (P<0.05) quantities (mg/100 g product) of monounsaturated (MUFA) and n3 polyunsaturated (PUFA) fatty acids (mainly alpha-linolenic acid), a lower (P<0.05) n6/n3 PUFA ratio and a higher (P<0.05) polyunsaturated/saturated fatty acid ratio. The replacement of raw meat material by walnut reduced (P<0.05) the cholesterol content and increased (more than 400 times) the amount of gamma-tocopherol. Iron, calcium, magnesium and manganese contents of 20W sample were greater (P<0.05) than in the control. Some changes induced by added walnut in the nutritional quality of the restructured product may present health benefits. PMID- 22063893 TI - The accuracy of predicting carcass composition of three different pig genetic lines by dual-energy X-ray absorptiometry. AB - The accuracy of dual energy X-ray absorptiometry (DXA) for predicting carcass composition was evaluated by applying this technology to 95 half-carcasses of gilts from three genetic lines of widely varying composition. The DXA measurements of total weight, fat and lean masses and bone mineral content were used to predict the dissected lean, fat, bone and weight of the major primal cuts and the overall carcass. The study showed that it is not necessary to correct, or rather adjust, the prediction equations between genetic lines, given the small decrease in the prediction error (less than 1.43%). Except for the prediction for loin bone weight, the results showed that incorporating more than one of the predictive variables derived from DXA or from direct carcass measurements into the regression models was not justified in terms of prediction accuracy. The best predictions were those for half-carcass weight and primal cut weights (R(2)>0.95). The prediction of dissected lean ranked second in accuracy (R(2)>0.85), with the exception of the belly. The equations using DXA measurements provide good estimation (R(2)>0.70) of the weight of fat in the carcass and primal cuts. However, DXA showed moderate accuracy (R(2)<0.66) in predicting bone weight, although greater accuracy was attained for loin bone weight using a two-variable prediction model. PMID- 22063894 TI - Biochemical and physical factors affecting discoloration characteristics of 19 bovine muscles. AB - Steaks from muscles (n=19 from nine beef carcasses) were evaluated over the course of retail display (0-, 1-, 2-, 3-, 4- or 5-d) for objective measures of discoloration (metmyoglobin, oxymyoglobin, L*-, a*-, and b*-values), reducing ability (metmyoglobin reductase activity (MRA), resistance to induced metmyoglobin formation (RIMF), and nitric oxide metmyoglobin reducing ability (NORA)), oxygen consumption rate (OCR), oxygen penetration depth, myoglobin content, oxidative rancidity, and pH. Muscles were grouped according to objective color measures of discoloration. M. longissimus lumborum, M. longissimus thoracis, M. semitendinosus, and M. tensor fasciae latae were grouped as "high" color stability muscles, M. semimembranosus, M. rectus femoris, and M. vastus lateralis were grouped as "moderate" color stability muscles, M. trapezius, M. gluteus medius, and M. latissimus dorsi were grouped as "intermediate" color stability muscles, M. triceps brachi - long head, M. biceps femoris, M. pectoralis profundus, M. adductor, M. triceps brachi - lateral head, and M. serratus ventralis were grouped as "low" color stability muscles, and M. supraspinatus, M. infraspinatus, and M. psoas major were grouped as "very low" color stability muscles. Generally, muscles of high color stability had high RIMF, nitric oxide reducing ability, and oxygen penetration depth and possessed low OCRs, myoglobin content, and oxidative rancidity. In contrast, muscles of low color stability had high MRA, OCRs, myoglobin content, and oxidative rancidity and low RIMF, NORA, and oxygen penetration depth. Data indicate that discoloration differences between muscles are related to the amount of reducing activity relative to the OCR. PMID- 22063895 TI - The effects of antioxidant combinations on color and lipid oxidation in n-3 oil fortified ground beef patties. AB - This study was carried out to determine an effective combination of chelators, reductants and free radical scavengers for enhancing color stability and minimizing lipid oxidation in muscle foods fortified with n-3 fatty acids. Chelators (sodium tripolyphosphate, STPP; sodium citrate, CIT), reductants (sodium erythorbate, ERY) and radical scavengers (butylhydroxyanisole, BHA; mixed tocopherols from two different sources, 30 or 95TOC; rosemary extract, ROSE) were incorporated in various combinations into ground beef (15% fat) with or without n 3 oil fortification (n=8). Individually, STPP and CIT had no significant effect on a* values except day 4, but showed higher a* values when combined with ERY (STPP+ERY and CIT+ERY) (P<0.05). CIT had lower hue angle values than STPP on days 4 and 6, but CIT+ERY showed more discoloration than STPP+ERY (P<0.05). CIT+ERY showed less lipid oxidation than CIT alone (P<0.05), whereas there was no difference between STPP and STPP+ERY. CIT+ERY+ROSE demonstrated higher a* values than CIT+ERY+95TOC on days 4 and 6 (P<0.05); there was no difference between ROSE and 95TOC groups when n-3 oil was incorporated into ground beef patties (P>0.05). The combination of ROSE and ERY appeared to be effective in slowing the decline of a* values. All antioxidant combinations were effective at delaying lipid oxidation when compared to CON or n-3. A combination of CIT, ERY and ROSE was most effective for stabilizing color and delaying lipid oxidation. PMID- 22063896 TI - Application of PLSR in correlating physical and chemical properties of pork ham with different cooling methods. AB - Partial least squares regression (PLSR) was applied to understand the relationship between physical and chemical properties of pork leg ham with different cooling treatments, i.e., cold room, air blast and vacuum cooling. The results indicated that overall 69.8% variation of physical matrix was explained by chemical matrix. For the univariate analysis of physical attributes, the results showed that gumminess (88.1%) and hardness (86.5%) were best explained by chemical matrix, followed by springiness (78.7%), Warner-Bratzler Shear force (61.3%), and a* (60.0%). Graphical display of the regression coefficients indicated that different cooling treatments had different effects on the physical property of pork ham. Therefore, to predict the physical quality with chemical attributes, separate regression formulations should be adopted for different cooling methods. These findings have practical importance in attempts to predict physical properties from chemical components. In addition, they can also be used to control the physical properties by adjusting the components in the meat system. PMID- 22063897 TI - Effects of breed and marination on the sensory attributes of pork from Large White and Hampshire-sired pigs. AB - The effects of breed and marination were tested for their effects on meat pH, water holding (marinade uptake and losses) and eating quality (tenderness, juiciness and flavour). Loins were removed from one side of 20 Large White-sired and 20 Hampshire-sired pigs after slaughter, cut into four pieces and injected to 112% of their initial weight with water, a polyphosphate-containing marinade (pH 7.7) or a high pH marinade (pH 10.3). An uninjected piece of loin served as control. Samples were left overnight and then frozen before being thawed, cooked and assessed by a trained ten member sensory panel using 1-8 category scales. Hampshires had higher intramuscular fat (0.95%) than Large Whites (0.62%) but otherwise the effects of breed were small compared with marination. Both marinades significantly increased meat pH from 5.5 (control) by 0.2U, significantly reduced the cooking loss and increased the meat yield from about 80% to 90%. Water-injected samples lost large amounts of added water as drip after thawing and had a yield (76%) similar to the control. Marinaded samples retained more water post-cooking. Both marinades significantly increased tenderness (p<0.001) and juiciness (p<0.001) by about 1.0U compared with the control (4.4 for tenderness and 4.2 for juiciness). Pork flavour, however, was significantly reduced (p<0.001) and abnormal flavour was significantly increased (p<0.001) by marination. Tenderness was positively correlated with pH after injection (0.83) and yield (0.75); juiciness was also positively correlated with pH after injection (0.78) and yield (0.87). The absence of any significant difference in eating quality between control and water-injected samples, and the relatively large effects of marination, suggest that retained water (after cooking) is crucial in determining perceived tenderness and juiciness in pork. PMID- 22063898 TI - Dietary creatine monohydrate affects quality attributes of Duroc but not Landrace pork. AB - Increased creatine content in the muscle may delay post mortem lactate formation and postpone the pH decline, hence potentially improving the water-holding capacity (WHC). Duroc and Landrace pigs were supplemented with 0, 12.5, 25 or 50g creatine monohydrate (CMH)/d for 5 days prior to slaughter. Meat from Longissimus dorsi (LD) of Duroc pigs had a higher WHC and pH at all times, lower colour determinants; a* (redness), b* (yellowness), L* (lightness) and was more juicy compared to that of Landrace pigs. Furthermore, higher pH(2h), pH(24h) and decreased colour determinants were observed in carcass sides exposed to a faster cooling profile. Dietary supplementation with CMH increased the body weight gain of both breeds. However, only meat from Duroc pigs had higher pH(30min) and pH(45min) (at 50g CMH/d) and WHC, but reduced redness (reduced in both breeds) and juiciness when supplemented with CMH compared to non-supplemented controls. PMID- 22063899 TI - The detection of horse and donkey using real-time PCR. AB - We have developed real-time PCR assays specific for horse and donkey, applicable to the detection of low levels of horse or donkey meat in commercial products. Primers, designed to the mitochondrial cytochrome b gene, were 3' mismatched to closely related and other commercial species. Amplification of non-target species DNA was prevented by truncation of primers at the 5' position, thereby conferring complete specificity. Both assays were highly sensitive and detected the presence of 1pg of donkey template DNA or 25pg of horse template DNA when assessed using dilutions of DNA in water. Model food samples, spiked with horse or donkey muscle and commercial products containing horse, were successfully tested for the presence of horse or donkey, demonstrating the applicability of the assays to food products. PMID- 22063900 TI - Should electrical stimulation be applied when cold shortening is not a risk? AB - This experiment was designed to show whether delayed high voltage stimulation (ES) is more beneficial than no stimulation (NS) to secure tenderness under circumstances where rigor conditions are difficult to control due to variations in carcass size, fatness and/or chilling capacity. Ten Charolais carcasses were split during slaughter, the left sides were stimulated at 45min post-mortem for 45s, and the right sides were left unstimulated. The carcass sides were then chilled at a medium chilling rate. Sarcomere length measurements confirm that there was neither cold nor heat shortening in the M. longissimus (LD). LD from ES sides aged for 2 days was more tender than non-stimulated LD (NES), although prolonged ageing eroded the advantage of ES to a non-significant advantage after 14 days. Initial tenderness differences coincided with lower 24h calpain activity, suggesting an early onset of proteolysis and ageing (tenderisation). In contrast to conventional early ES, delayed ES, appears to be beneficial for the early development of tenderness without too much interference with enzyme. Myofibril fragment length (MFL) was a good indicator of the development of tenderness during prolonged ageing but not for the early post-mortem variation in tenderness. No colour (L*, a*, b*) differences, occurred due to stimulation treatment, while drip loss was slightly higher at 24h post-mortem for ES meat. PMID- 22063901 TI - Effect of salt and transglutaminase (TG) level and processing conditions on quality characteristics of phosphate-free, cooked, restructured pork shoulder. AB - Six treatments of phosphate-free restructured cooked pork shoulder were produced with two salt levels (2% and 1%) and three transglutaminase levels (0%, 0.075% and 0.15%) under two processing conditions (72 degrees C/65 min and 78 degrees C/65 min). Salt level significantly affected (p<0.05) the chemical composition, the cooking losses, the colour, the sensory attributes and the overall acceptability of the product. Transglutaminase level affected (p<0.05) only the consistency and the overall acceptability. The processing conditions on the contrary, affected the moisture and the protein content, the cooking losses, the consistency and the juiciness of restructured cooked pork shoulder. Transglutaminase can be used at a level of 0.15% with reduced salt level (1%) and processing at 72 degrees C/65 min to produce phosphate-free restructured cooked pork shoulder with acceptable sensory attributes. PMID- 22063905 TI - The mathematical relationship between dishware size and portion size. AB - Portion size has increased considerably over the past few decades and one influencing factor is dishware size. Using mathematical models we investigated how dish size affects the potential energy available in a meal. Two types of plate filling - flat and conical - were modelled for a range of plate sizes and energy densities, then compared to recommended daily energy requirements from Australian guidelines. Bowl filling was also modelled. Results indicate that a small increase in dishware size can lead to a substantial increase in energy available to be consumed, particularly if food is energy dense. This reinforces the need to consider dishware size when developing strategies to prevent over consumption. PMID- 22063904 TI - Both left and right posterior parietal activations contribute to compensatory processes in normal aging. AB - Older adults often exhibit greater brain activation in prefrontal cortex compared to younger adults, and there is some evidence that this increased activation compensates for age-related neural degradation that would otherwise adversely affect cognitive performance. Less is known about aging and compensatory recruitment in the parietal cortex. In this event-related functional magnetic resonance imaging study, we presented healthy young and old participants with two Stroop-like tasks (number magnitude and physical size). In young, the number magnitude task activated right parietal cortex and the physical size task activated left parietal cortex. In older adults, we observed contralateral parietal recruitment that depended on the task: in the number magnitude task older participants recruited left posterior parietal cortex (in addition to the right parietal activity observed in young) while in the physical size task they recruited right (in addition to left) posterior parietal cortex. In both cases, the additional parietal activity was associated with better performance suggesting that it played a compensatory role. Older adults also recruited left prefrontal cortex during both tasks and this common activation was also associated with better performance. The results provide evidence for task specific compensatory recruitment in parietal cortex as well as task-independent compensatory recruitment in prefrontal cortex in normal aging. PMID- 22063906 TI - Effect of supplemental vitamin E on the color and case-life of top loin steaks and ground chuck patties in modified atmosphere case-ready retail packaging systems. AB - Retail packages (n=384; 24 of each product in each treatment by storage combination) of ground chuck patties (GC) and top loin steaks (TL) were used to evaluate effects of dietary supplementation of Vitamin E (VITE) to cattle on product performance when packaged in a modified atmosphere case-ready packaging system (MAP). Products from control (CON) animals and cattle fed 500 IUanimal( 1)day(-1) for 124 days were evaluated. Color properties, lipid oxidation, and alpha-tocopherol concentration were measured. Analysis revealed a higher concentration of alpha-tocopherol in VITE samples compared with control samples for top loin steaks and ground chuck patties. In comparison to CON cuts, maximum display life was improved by 3 and 0.9 days with VITE for top loin steaks and ground chuck patties, respectively. This study suggests that VITE supplementation would be beneficial in improving lipid and color stability of beef products stored in high oxygen MAP packaging systems. PMID- 22063907 TI - Lipid and colour stability of Milano-type sausages: effect of packing conditions. AB - Lipid and colour oxidative changes in Milano-type fermented sausages were studied in relation to packing conditions and extended storage under fluorescent light. Matured sausages were sliced and packed under vacuum or in protective atmosphere (100% N(2)) and exposed in a display cabinet to mimic commercial conditions of light and temperature for 2 months. Lipid oxidation was measured by the determination of thiobarbituric acid reactive substances (TBARS) and cholesterol oxidation products (COP), whereas the oxidation of nitrosylmyoglobin was evaluated by a trained sensory panel. Lipid oxidation and discolouration were positively related in vacuum-packed sausages: TBARS and COP values increased significantly concurrently with increasing brown scores. Protective atmosphere came out to be more efficient than vacuum in controlling fatty acid oxidation and, to a lesser extent, cholesterol and pigment degradation: TBARS values remained constant during the whole storage period whereas cholesterol oxides and brown colour scores gradually increased but remained lower than those of vacuum packed sausages. Higher residual oxygen in vacuum packing could be responsible for the observed differences in oxidative stability. PMID- 22063908 TI - Salt and phosphate effects on the gelling process of pressure/heat treated pork batters. AB - Thermal instability and setting was induced in pork by comminution, and the presence of NaCl and a salt mixture. Meat batter production by cooking (70 degrees C/30 min) produced almost complete protein denaturation and aggregation, mostly by hydrophobic interactions. It led to a firm and elastic gel with high water holding capability, these properties being greater in the gel with sodium tripolyphosphate. Pressurisation (400 MPa/70 degrees C/30 min) produced partial protein denaturation and differential scanning calorimetry and electrophoresis showed that both salt-soluble and salt-insoluble proteins remained native-like after treatment. The presence of these proteins, stabilised by hydrogen-bonds, were responsible for reductions in the mechanical properties but enhancement in water holding of the pressurised products. Tripolyphosphate partially counteracted the pressure effects in the pressure/heat combination. PMID- 22063909 TI - Meat pH and meat fibre direction effects on moisture diffusivity in salted ham muscles dried at 5 degrees C. AB - The effects of meat pH and meat fibre direction on the effective moisture diffusivity coefficient (D(e)) in salted ham muscles dried at 5 degrees C and 80% of air relative humidity were studied. Parallelepipedic meat samples from different muscles in the ham (Gluteus medius, Semimembranosus and Biceps femoris) were salted (0.08 kg NaCl/kg d.m.) and drying was only allowed through two faces of the sample by covering the other faces with PVC film. D(e) values were determined by Fick's 2nd law. D(e) parallel to the meat fibre direction in samples of Gluteus medius muscles was not affected by pH in the range 5.3-6.7. No significative differences in D(e) between the three muscles were detected (D(e) values ranged from 2.03*10(-11) to 2.55*10(-11) m(2)/s). D(e) perpendicular to meat fibre direction was 31% lower than D(e) parallel. The fibre direction effect was independent of the muscle. PMID- 22063910 TI - Factors affecting the level of boar taint in entire male pigs as assessed by consumer sensory panel. AB - A sensory study was conducted to determine consumer responses to meat from entire male pigs in order to evaluate different factors involved in causing boar taint, including 16-androstene steroids, skatole, size of accessory sexual glands and live weight. Pork chops from 33 entire Yorkshire male pigs were divided into three groups according to the levels of 16-androstene steroids in salivary glands, high (H; 56-114 MUg/g), medium (M; 35-55 MUg/g) and low (L; 26-6 MUg/g), and were distributed among 59 families. Pork chops from gilts were used as control (C). The families were asked to rate liking of cooking aroma, flavour and texture, and overall liking. Consumer ratings were best related to the size of bulbourethral gland and salivary gland, followed by the levels of 16-androstene steroids in salivary gland. Meat from the L group received similar ratings to the C group, except the ratings for texture and overall liking were better than the C group. M samples were liked similarly to C, with the exception of some samples that had high fat skatole levels and which were liked less. H samples were liked less than C. The samples evaluated at the beginning of the experiment were liked more than those evaluated afterwards indicating sensitization of consumers to boar taint. The results indicate that levels of 16-androstenes in salivary glands can be used to estimate boar taint due to 16-androstenes; however, skatole measurements also need to be included. In addition, consumers are sensitive to some other maturity-related factors, which need to be considered when estimating the levels of boar taint. The effect of sensitization of consumers to boar taint requires more study. PMID- 22063911 TI - Combined effects of pre-slaughter treatments and lairage time on carcass and meat quality in pigs of different halothane genotype. AB - The effect of two different lairage times on meat quality was investigated in pigs with different halothane genotype previously submitted to controlled pre slaughter treatments. One hundred and ninety nine Italian heavy pigs were loaded by ramp or lift and transported unmixed for 1 h to the abattoir at a stocking density of either <0.4 or >0.6 m(2) per 100 kg pigs. After unloading, an equal number of animals within each previous treatment was held in lairage for 2 h or overnight (22 h) before slaughter. Carcass and meat quality and incidence of skin damage were evaluated. Longer lairage did not negatively affect carcass traits and reduced the incidence of PSE meat without increased DFD occurrence. It also seriously increased the amount of skin damage due to fighting, resulting in long fasting. Pre-slaughter treatments and halothane genotype showed a negligible effect on the response to the resting time. PMID- 22063912 TI - Raw-meat packaging and storage affect the color and odor of irradiated broiler breast fillets after cooking. AB - Raw breast fillets were divided into two groups and either vacuum or aerobically packaged. The fillets in each group were subdivided equally into two groups and then irradiated at 0 or 3 kGy using a Linear Accelerator. After 0, 3 and 7 days of storage at 4 degrees C, fillets were cooked in an 85 degrees C water bath (cook-in-bag) to an internal temperature of 74 degrees C. Oxidation-reduction potential (ORP) of raw fillets was measured before cooking, and color and sensory characteristics were analyzed after cooking. Irradiation decreased the ORP of meat, but the potential in aerobically packaged fillets increased during storage. After cooking, color a*-value of irradiated fillets was higher than that of the non-irradiated. Irradiation of raw meat also changed color L* and b* values after cooking. Aerobic storage reduced the redness of cooked meat induced by irradiation. Irradiated raw broiler fillets stored for 0 day and 3 day under aerobic conditions before cooking produced a oxidized chicken-like odor. The odor, however, disappeared after 7 days of storage under aerobic conditions before cooking. For raw broiler samples stored under vacuum conditions, significant differences in color and odor between irradiated and non-irradiated fillets remained throughout the 7-day storage period after cooking. Irradiation had only a minor influence on lipid oxidation of raw breast fillets as indicated by low TBARS values. This study indicates that the effect of irradiation on color and odor of broiler breast fillets after cooking can be reduced significantly through shelf-display of raw fillets under aerobic conditions. Storage under vacuum conditions before cooking is not effective in reducing irradiation-induced changes in the color and odor of breast fillet after cooking. PMID- 22063913 TI - Porcine troponin I: a thermostable species marker protein. AB - In this study, we confirmed our previous hypothesis that the 24 kD thermostable skeletal muscle protein (TSMP) recognized by a panel of porcine-specific monoclonal antibodies (MAbs) is skeletal troponin I (sTnI). The TSMP and sTnI purified from porcine muscle have identical electrophoretic mobilities, isoelectric characteristics, and specific antigenicities. The heterogeneity of sTnI between porcine and other species, and between porcine sTnI and other troponin subunits or cardiac isoforms can be immunologically differentiated by the MAbs. Heat treatment of sTnI up to 126 degrees C for 120 min did not diminish its solubility and antigenicity. The antigenic specificity and thermal stability of sTnI indicate its potential as a thermostable species marker for the identification of the origin of meats in severely heated products. PMID- 22063914 TI - Fatty acid and triglyceride profiles of intramuscular and subcutaneous fat from fresh and dry-cured hams from Hairless Mexican Pigs. AB - The study was designed to compare the fatty acid profiles and triglyceride composition of subcutaneous and intramuscular fat of raw and cured hams from Hairless Mexican Pigs. Curing (180 days) was developed throughout several ordered steps: salting, stabilization, drying and ripening. For the salting step, hams were rubbed with nitrate salt, and kept on salt 1 day per kilogram at 0-4 degrees C and at relative humidity of 80-85%. The rest of the process consisted of small increments of temperature (from 0-24 degrees C) and small decrements of relative humidity (from 82-68%). The curing process decreased (P<0.05) significantly the proportion of unsaturated fatty acids (raw: 59.2+/-0.3% and cured: 55.3+/-0.4%) and increased the saturated ones (raw: 34.4+/-0.3% and cured: 39.4+/-0.5%). Subcutaneous and intramuscular fat had similar (P>0.05) percentages of unsaturated (57.60+/-0.3 and 56.88+/-0.4%, respectively) and saturated fatty acids (37.5+/-0.33 and 38.3+/-0.4%, respectively). With the exception of the monopalmitate, the curing process decreased (P<0.05) the levels of all acylglycerols studied. PMID- 22063915 TI - Immunohistochemical detection of brain tissue in heated meat products. AB - Immunohistochemical methods were used to determine whether brain tissue could be detected in test batches of meat products prepared with known levels of this tissue (0, 1, 5, 10, or 20% bovine brain tissue or 5% porcine brain tissue). Four different, commercially-available antibodies were examined: anti-Neurofilament (anti-NF), anti-MyelinBasicProtein (anti-MBP), anti-NeuronSpecificEnolase (anti NSE) and anti-GlialFibrillaryAcidicProtein (anti-GFAP). Results obtained with the four antibodies differed with the heat treatment applied to the products (pasteurisation or sterilisation). The amount of immunoreaction product in the raw meat product varied with the antibody, even when the sample contained the same amount of brain tissue. The staining pattern also varied with the antibody. Overall, the anti-MBP antibody proved to be most useful in detecting brain tissue in finely comminuted heated meat products. PMID- 22063916 TI - Quality of comminuted sausages formulated from mechanically deboned poultry meat. AB - Comminuted sausages formulated with mechanically deboned poultry meat-MDPM (turkey or chicken, frame or neck) treated in different ways before production (vacuum packed MDPM or air packed skeletons deboned at production) and stored frozen for 6 or 18 weeks have been studied using a full-factorial design and chemical, physical and sensory analysis. MDPM was obtained from a Beehive separator. Comminuted sausages with MDPM from turkey frames, stored at -25 degrees C as skeletons, packed in air for 18 weeks developed marked rancid odour and flavour which could also be detected by thiobarbituric acid reactive substances (TBARS) and the concentration of volatile compounds. Vacuum packed mechanically deboned meat irrespective of species and carcass part could be stored for up to 18 weeks and used in formulation of sausages without any serious changes in their sensory profiles. Instrumental colour differences between sausages were mainly due to species. Turkey sausages were darker, redder and less yellow than chicken sausages. Moisture and fat contents were influenced by carcass part and to a lesser extent depended on species and storage time. Principal least squares regression (PLS2) showed close relationships between instrumental parameters and sensory attributes. TBARS, hexanal and volatile compounds were highly correlated with rancid flavour while redness (a(*)) was strongly related to sensory colour hue and colour strength. PMID- 22063917 TI - Cooked sausage batter cohesiveness as affected by sarcoplasmic proteins. AB - In the first trial, m. semitendinosus and m. biceps femoris were held at 0, 10 and 35 degrees C until they entered rigor, and in the second trial, minced m. semitendinosus was washed in water for 15, 30, 45 or 60 min. The samples from both the trials were then used to make a finely comminuted sausage batter. Soluble sarcoplasmic protein (SSP) levels decreased with increasing rigor temperature (P < 0.05) or washing (P < 0.01). Cooked batter shear stress was not affected by SSP level, but batter shear strain decreased with the decreasing SSP level associated with an increasing rigor temperature (P < 0.05) or washing (P < 0.01). Reducing the SSP content lowered the cook yield (P < 0.05) and emulsion stability (P < 0.01) of the batter from the washed samples compared to that of controls. The results suggest that sarcoplasmic proteins are important in determining the strain values (cohesiveness) of cooked sausage batter. PMID- 22063918 TI - Perimysial collagen crosslinking and meat tenderness in Belgian Blue double muscled cattle. AB - The relationship between intramuscular collagen and five collagen crosslink concentrations, and the tenderness of meat from Belgian Blue normal, heterozygous double-muscled (DM) and homozygous DM cattle was investigated using M. semitendinosus (St) and M. gluteobiceps (Gb). The histidinohydroxymerodesmosine (HHMD) concentration (per mol collagen) in St was less in DM animals than normal animals. Concentrations (per gram of wet meat) of HHMD and Erlich chromogen (EC) in Gb, and HHMD, EC, dihydroxylysinorleucine (DHLNL) and hydroxylysinorleucine (HLNL) in St were also lower in DM animals than normal animals. Shear force of raw meat was significantly greater in normal animals than DM for both muscles; cooked meat shear force was greater in the normal animals for the Gb muscles only, showing a good correlation with sarcomere length. Most correlations between shear force and collagen or crosslink concentrations were not significant and those that were highly significant were generally weak. PMID- 22063919 TI - Contribution of major structural changes in myofibrils to rabbit meat tenderisation during ageing. AB - The contribution of major structural (myofibrillar fragmentation upon mechanical treatment) and ultra-structural (Z-line degradation, loss of electron density of M-line, transversal disruption of sarcomeres at N(2)-line level, longitudinal fissure of myofibrils, and loss of transversal alignments of Z- and M-lines) changes in myofibrils to rabbit (Oryctolagus cuniculus L.) meat tenderisation, during the ageing period (9 days at +4 degrees C), was studied for different types of muscle (type I, semimembranosus proprius; type IIB, semimembranosus accessorius; and type IID, psoas major). The results strongly suggest that myofibrillar structure weakening at N(2)-line level (evaluated by myofibrillar fragmentation upon mechanical homogenisation and observed by transversal disruption of sarcomeres), which is very likely mediated by cysteine endopeptidases, might be the major structural change responsible for rabbit meat tenderisation during ageing. Both myofibrillar fragmentation and transversal disruption of sarcomeres are good ageing indices for rabbit meat. The other major ultra-structural changes in myofibrils appear to have no major role in rabbit meat tenderisation at refrigeration temperatures. Finally, it is proposed that meat tenderisation during ageing depends mainly on the specific cleavage of titin molecules/filaments and nebulin molecules, at their susceptible sites located at or very close to the N(2)-line region (extensible segment and near C-terminus, respectively), mediated by cysteine endopeptidases (possibly calpains). PMID- 22063920 TI - A novel fused 1,2,4-triazine aryl derivative as antioxidant and nonselective antagonist of adenosine A(2A) receptors in ethanol-activated liver stellate cells. AB - It has been detected that hepatic adenosine A(2A) receptors play an active role in the pathogenesis of hepatic fibrosis and suggest a novel therapeutic target in the treatment and prevention of hepatic cirrhosis. In this paper we examined if our new triazine derivative (IMT) can inhibit ethanol-induced activation of HSCs measured as increased alpha-SMA, collagen synthesis and enhanced oxidative stress in rat liver stellate cells. We also investigated its influence on cytokines (TGF beta, TNF-alpha) synthesis, MMP-2 and TIMP-1 production and ethanol-induced intracellular signal transduction. Moreover, with using of known adenosine A(2A) receptor agonist (CGS 21680), and antagonist (SCH 58261) we examined if this triazine derivative acts on adenosine receptors. We detected a strong antagonistic action of new triazine derivative (IMT) on ethanol-induced rat liver stellate cells activation, observed as a significant decrease in alpha-SMA, collagen synthesis, reactive oxygen species production, TGF-beta, TNF-alpha, MMP 2 and TIMP-1 production as well as JNK, p38MAPK, NFkappaB, IkappaB, Smad3 phosphorylation. Moreover, IMT strongly inhibited activation of stellate cells by known selective agonist of adenosine A(2A) receptor (CGS 21680). When known A(2A) receptor antagonist (SCH 58261) was used together with IMT this effect was not spectacular. Additionally, only slight enhancement of inhibition was observed when cells were pretreated both IMT with SCH 58261, hence we suppose that IMT acts as nonselective antagonist of A(2A) receptors, and, besides its antioxidant activity, also by this way inhibited ethanol-induced stellate cell activation. PMID- 22063921 TI - Effect of vicanicin and protolichesterinic acid on human prostate cancer cells: role of Hsp70 protein. AB - With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on prostate cancer cells, in the present study, we evaluated the effect of five lichen secondary metabolites the depsides atranorin (1), diffrattaic (2) and divaricatic (3) acids, the depsidone vicanicin (4) and the protolichesterinic acid (5) on cell growth in androgen-sensitive (LNCaP) and androgen-insensitive (DU-145) human prostate cancer cells. The cell viability was measured using MTT assay. LDH release, a marker of membrane breakdown, was also measured. For the detection of apoptosis, the evaluation of DNA fragmentation (COMET assay) and caspase-3 activity assay were employed. The expression of Bcl-2, Bax, TRAIL, COX 2, NOS2 and Hsp70 proteins was detected by western blot analysis. Generation of reactive oxygen species was measured by using a fluorescent probe. It was observed that atranorin (1), diffrattaic (2) and divaricatic (3) acids showed a lower activity inhibiting the prostate cancer cells only at more high concentrations (25 and 50MUM). Whereas compounds vicanicin (4) and protolichesterinic acid (5) showed a dose-response relationship in the range of 6.25-50MUM concentrations in DU-145 and LNCaP cells, activating an apoptotic process. The novel finding, in the present study, is that apoptosis induced by these compounds appears to be mediated, at least in part, via the inhibition of Hsp70 expression, that may be correlated with a modulation of redox-sensitive mechanisms. The combination of vicanicin (4) and protolichesterinic acid (5) with other anti-prostate cancer therapies could be considered a promising strategy that warrants further in vivo evaluation. PMID- 22063922 TI - Ontogeny of gene expression of group IB phospholipase A2 isoforms in the red sea bream, Pagrus (Chrysophrys) major. AB - The red sea bream (Pagrus major) was previously found to express mRNAs for two group IB phospholipase A(2) (PLA(2)) isoforms, DE-1 and DE-2, in the digestive organs, including the hepatopancreas, pyloric caeca, and intestine. To characterize the ontogeny of the digestive function of these PLA(2)s, the present study investigated the localization and expression of DE-1 and DE-2 PLA(2) genes in red sea bream larvae/juveniles and immature adults, by in situ hybridization. In the adults, DE-1 PLA(2) mRNA was expressed in pancreatic acinar cells. By contrast, DE-2 PLA(2) mRNA was detected not only in digestive tissues, such as pancreatic acinar cells, gastric glands of the stomach, epithelial cells of the pyloric caeca, and intestinal epithelial cells, but also in non-digestive ones, including cardiac and lateral muscle fibers and the cytoplasm of the oocytes. In the larvae, both DE-1 and DE-2 PLA(2) mRNAs first appeared in pancreatic tissues at 3 days post-hatching (dph) and in intestinal tissue at 1 dph, and expression levels for both gradually increased after this point. In the juvenile stage at 32 dph, DE-1 PLA(2) mRNA was highly expressed in pancreatic tissue, and DE-2 PLA(2) mRNA was detected in almost all digestive tissues, including pancreatic tissue, gastric glands, pyloric caeca, and intestine, including the myomere of the lateral muscles. In conclusion, both DE-1 and DE-2 PLA(2) mRNAs are already expressed in the digestive organs of red sea bream larvae before first feeding, and larvae will synthesize both DE-1 and DE-2 PLA(2) proteins. PMID- 22063923 TI - JD-30, an active fraction extracted from Danggui-Shaoyao-San, decreases beta amyloid content and deposition, improves LTP reduction and prevents spatial cognition impairment in SAMP8 mice. AB - JD-30 is an active fraction extracted from Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription. We previously showed that JD-30 could alleviate cognitive dysfunction of the mice induced by intracerebroventricular injection of beta-amyloid (Abeta). However, data remain scarce on the effect of JD-30 on an Alzheimer's disease (AD) model and the underlying mechanisms are unknown. Further detailed studies on the effects of JD-30 on spatial cognition of senescence-accelerated mouse prone 8 (SAMP8), a suitable rodent model for cognitive impairment of aged subjects were investigated to elucidate the possible mechanisms. Long-term treatment with JD-30 significantly decreased the prolonged latency of SAMP8 in the Morris water-maze test. It also ameliorated the reduction of long-term potentiation (LTP) and reduced the damage of neurons in the hippocampus of SAMP8. Finally, JD-30 decreased the content and deposition of Abeta in the brain of SAMP8. The results show that JD-30 improves deterioration of spatial learning and memory in the SAMP8 mouse model, and by decreasing the content and deposition of Abeta, neuronal activity and synaptic plasticity improve, suggesting one of the mechanisms involved. PMID- 22063924 TI - Hypocapnia-dependent facilitation of augmented breaths: observations in awake vs. anesthetized rats. AB - We investigated whether commonly used injectable laboratory anesthetics alter the regulation of augmented breaths (ABs) in different respiratory backgrounds. Male rats were studied on three separate experimental days, receiving one of three injections in randomized order: ethyl carbamate ('urethane'; 1.2mgkg(-1)), ketamine/xylazine (ket/xyl; 80/10mgkg(-1)), or normal saline. Following each of the three interventions, breathing was monitored during 15min exposures to normoxia (room air), hypoxia (10% O(2)) and hypoxia+CO(2) (10% O(2), 5% CO(2)). Urethane anesthesia completely eliminated ABs from the breathing rhythm in room air conditions (p<0.001), and decreased the hypocapnia-dependent component of this response (p<0.001). ket/xyl left the normal incidence of ABs in room air breathing intact but significantly suppressed the hypoxia-induced facilitation of ABs (p=0.0015). These results provide the first clear evidence that laboratory anesthesia can profoundly alter the regulation of ABs including the hypocapnia dependent component of their facilitation. PMID- 22063926 TI - Genomic approaches to economic trait loci and tissue expression profiling: application to muscle biochemistry and beef quality. AB - Genetic and environmental factors profoundly alter the phenotypes of animals. Nowadays, genomics allows large-scale analysis of gene characteristics (structural genomics) and expression (functional genomics). Genome mapping, comparative genomics and identification of quantitative trait loci and polymorphisms are the subject of active investigation to gain a better knowledge of the structure and function of genes. Gene expression profiling using DNA microarrays and proteomics holds great promise for the study of regulatory events which control the final biological functions. Combined with classical genetics and muscle biochemistry to form an integrative biology, these new approaches will bring a better understanding of complex traits and physiological processes. Major applications in meat science could be, for cattle, (1) the identification of new predictors of quality traits (for instance, tenderness), (2) the monitoring of beef quality (including traceability) through the production systems (nutrition level, growth path, grass-feeding), and (3) the improvement of animal selection (markers and gene assisted selection) which may also include quality traits. PMID- 22063925 TI - Structure-activity relationships in rodent diaphragm muscle fibers vs. neuromuscular junctions. AB - The diaphragm muscle (DIAm) is a highly active muscle of mixed fiber type composition. We hypothesized that consistent with greater activation history and proportion of fatigue-resistant fibers, neuromuscular transmission failure is lower in the mouse compared to the rat DIAm, and that neuromuscular junction (NMJ) morphology will match their different functional demands. Minute ventilation and duty cycle were higher in the mouse than in the rat. The proportion of fatigue-resistant fibers was similar in the rat and mouse; however the contribution of fatigue-resistant fibers to total DIAm mass was higher in the mouse. Neuromuscular transmission failure was less in mice than in rats. Motor end-plate area differed across fibers in rat but not in mouse DIAm, where NMJs displayed greater complexity overall. Thus, differences across species in activation history and susceptibility to neuromuscular transmission failure are reflected in the relative contribution of fatigue resistant muscle fibers to total DIAm mass, but not in type-dependent morphological differences at the NMJ. PMID- 22063927 TI - Sensory aspects of consumer choices for meat and meat products. AB - The topics discussed in this paper are the changing demand for meat and the factors that influence this demand. These factors include increased health concerns, change in demographics, the need for convenience, changes in the distribution of meat, and price. Finally, the paper covers the meat industry's need for understanding the consumer and the measurement methods used to assess consumer preferences. PMID- 22063928 TI - Effects of fatty acids on meat quality: a review. AB - Interest in meat fatty acid composition stems mainly from the need to find ways to produce healthier meat, i.e. with a higher ratio of polyunsaturated (PUFA) to saturated fatty acids and a more favourable balance between n-6 and n-3 PUFA. In pigs, the drive has been to increase n-3 PUFA in meat and this can be achieved by feeding sources such as linseed in the diet. Only when concentrations of alpha linolenic acid (18:3) approach 3% of neutral lipids or phospholipids are there any adverse effects on meat quality, defined in terms of shelf life (lipid and myoglobin oxidation) and flavour. Ruminant meats are a relatively good source of n-3 PUFA due to the presence of 18:3 in grass. Further increases can be achieved with animals fed grain-based diets by including whole linseed or linseed oil, especially if this is "protected" from rumen biohydrogenation. Long-chain (C20 C22) n-3 PUFA are synthesised from 18:3 in the animal although docosahexaenoic acid (DHA, 22:6) is not increased when diets are supplemented with 18:3. DHA can be increased by feeding sources such as fish oil although too-high levels cause adverse flavour and colour changes. Grass-fed beef and lamb have naturally high levels of 18:3 and long chain n-3 PUFA. These impact on flavour to produce a 'grass fed' taste in which other components of grass are also involved. Grazing also provides antioxidants including vitamin E which maintain PUFA levels in meat and prevent quality deterioration during processing and display. In pork, beef and lamb the melting point of lipid and the firmness/hardness of carcass fat is closely related to the concentration of stearic acid (18:0). PMID- 22063929 TI - Microbiological safety standards and public health goals to reduce foodborne disease. AB - Even though microbiological standards have been promulgated for many decades, their utility has sometimes been questioned, and this is one reason that performance standards associated with programs like HACCP in processing plants and now in other food industries have been espoused. The public has an increasing concern over food safety and perceives a zero tolerance policy (i.e. no pathogens in a sample of food) and strict enforcement with punitive consequences for failure to comply is the answer to making food safer. At present, there is no clear connection between government policy and a reduction in foodborne illness. Although national disease statistics may show gradual declines over long periods for some pathogens associated with food, other problems, including new pathogens, tend to emerge. International bodies and some governments, however, are increasingly considering adopting a risk-based approach to managing a food supply, with the potential for introducing the Acceptable Level of Protection (ALOP) and Food Safety Objectives (FSOs) concepts. These make it possible to see a connection between a goal for disease reduction and what industry must do to accomplish this with specific objectives through performance standards and microbiological testing. However, it may not be easy to apply this approach for all types of industries and pathogens and in developing countries. PMID- 22063930 TI - Prediction of technological and organoleptic properties of beef Longissimus thoracis from near-infrared reflectance and transmission spectra. AB - Technological and organoleptic properties of beef cuts were predicted by near infrared (NIR) spectroscopy. Spectra were collected on 189 beef Longissimus thoracis muscle samples using, transmission (NIRT) and reflectance with a probe. Quality assessment and NIR recordings were performed on sliced loin after 2 and 8 days ageing. Partial least squares regression yielded determination coefficients of cross-validation (R(2)(cv)) of 0.12-0.25 for the prediction of Warner-Bratzler Peak Shear Force in reflectance and 0.15-0.41 in transmission. Higher R(2)(cv) were obtained for L* parameter (0.83-0.85), a* (0.39-0.49) and b* (0.73-0.75) with reflectance. Predictions of drip loss and cooking loss were less accurate with a R(2)(cv) range of 0.38 to 0.54 and 0.25 to 0.47, respectively. The NIR spectra collected on fresh meat show good potential to predict CIE L* and b* parameters in reflectance mode. PMID- 22063931 TI - Evaluation of fat sources on cholesterol and lipoproteins using pigs selected for high or low serum cholesterol. AB - At approximately 8 weeks of age, four-way cross (Chester White*Landrace*Large White*Yorkshire) pigs (n=24) were selected based on genetically high (H) or low (L) serum cholesterol levels-12 from each genetic group-to determine the relationship between genetics, fat source, and sex class on plasma cholesterol, growth, carcass characteristics, and cholesterol and lipid content of muscle and adipose tissues. Boars and gilts, six each from the two genetic groups, were assigned randomly to one of three dietary treatments for 46 days. A standard grower diet was modified to include beef tallow (T), corn oil (CR) or coconut oil (CC), and the pigs were given ad libitum access to feed. Cholesterol was added to each diet to ensure the diets contained the same amount of cholesterol. Except for the plasma lipids, there were no differences between boars and gilts at the initial evaluation or at the end of the treatment; therefore, sex means were pooled for statistical analyses. Body weight was unaffected by diet on days 18, 29 or 46. Blood samples were taken on days 1, 29, and 46 via the anterior vena cava. Plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL) concentrations were greater in the H than L groups (overall TC in H and L pigs=150 and 124 mg/dl, respectively, and LDL in H and L pigs=105 and 76 mg/dl, respectively). Pigs fed diets containing saturated fats had greater TC and LDL than pigs fed unsaturated fats (TC=165, 149, and 126 mg/dl for T, CC, and CR diets, respectively, and LDL=108, 88, and 77 mg/dl for T, CC, and CR diets, respectively). There were significant time*gene*sex interactions for both TC and LDL yielding subtle differences in the response of the sexes from the two genetic groups over time. Pigs were slaughtered on day 46, and carcass data were collected. There were no differences in fat at the first rib, 10th rib, last rib, or last lumbar vertebra, but differences (P <0.05) were found between genetic groups for M. longissimus thoracis et lumborum (LTL) muscle area (H=21.0+/-0.8 cm(2), L=18.1+/-1.0 cm(2)) and USDA muscle score (H=2.1+/-0.1, L=1.7+/-0.1). There were no genetic or diet effects for cholesterol content of pre-rigor or post-rigor LTL muscle. Neither genetics nor dietary treatment affected the cholesterol content of the adipose tissue. There were no differences in fat percentage between genetic groups for muscle or adipose tissue. There were differences (P <0.05) in total lipid content among the dietary treatments for the pre-rigor (T=6.0+/-0.6%, CC=4.3+/-0.3%, CN=3.9+/-0.5%) and post-rigor (T=6.4+/ 0.9%, CC=4.1+/-0.3%, CN=5.0+/-0.4%) LTL. Cholesterol accretion in muscle and adipose tissues of growing pigs was not influenced by source of fat in the diet or by their genetic propensity for high or low plasma cholesterol. PMID- 22063932 TI - Effect of irradiation on the quality of turkey ham during storage. AB - Effect of electron-beam irradiation on the quality of ready-to-eat (RTE) turkey ham was studied. Turkey hams were purchased from local stores and sliced into 0.5 cm-thick pieces and vacuum packaged. The ham samples were randomly separated into three groups and irradiated at 0, 1, or 2 kGy, and stored at 4 degrees C for up to 14 days. Volatiles, color, TBARS values and sensory characteristics were determined to compare the effect of irradiation and storage on the quality of RTE turkey ham. Irradiation had little effects on color and TBARS values of RTE turkey hams. Sensory analysis indicated that sulfury odor increased as irradiation dose increased, and the contents of sulfur compounds in irradiated RTE turkey hams were higher (P <0.05) than those in nonirradiated samples. Irradiation increased (P <0.05) the production of acetaldehyde, which could be related to a metal-like flavor in irradiated hams. However, overall quality changes in RTE turkey hams by irradiation up to 2 kGy were minor. PMID- 22063933 TI - In situ investigation of the calcium-induced proteolytic and salting-in mechanisms causing tenderization in calcium-enhanced muscle. AB - The objective of this experiment was to explore the mechanism(s) of calcium induced tenderization in calcium-enhanced beef muscle. At 72 h postmortem, beef strip loins (n=15) were injected (9% by weight) with 0.0, 0.05, 0.1, 0.2, or 0.4 M calcium chloride (CaCl(2)) with and without 0.05 M zinc chloride (ZnCl(2)), and aged until 15 days postmortem. Warner-Bratzler shear force peak values indicated that addition of ZnCl(2) drastically inhibited tenderization; however, enhancement with CaCl(2) still tended to reduce shear values (P=0.07; 0.55 kg) when ZnCl(2) was present. In the absence of ZnCl(2), the 0.2 and 0.4 M CaCl(2) treatments were 18.9 and 32.1% more (P<0.05) tender than the 0.0 M CaCl(2) treatment. SDS-PAGE indicated that addition of zinc reduced breakdown of troponin T into ~31 and ~28 kDa components. Transmission electron micrographs indicated that addition of CaCl(2) without ZnCl(2) caused more frequent Z-line fractures and increased lateral spreading of myofibrils. These results suggest that both calcium-activated enzymatic activity and a non-enzymatic salting-in effect contributed to tenderization of calcium-enhanced muscle. However, the enzymatic mechanism reduced toughness 2.9- to 7.5-fold more than the non-enzymatic mechanism. Calcium-activated enzymatic degradation appears to be the major tenderization mechanism and non-enzymatic salting-in of calcium ions appears to be a minor tenderization mechanism, even at high calcium concentrations. PMID- 22063934 TI - Effects of micro-perforated film on the quality and shelf life improvements of pork loins during chilled storage. AB - The effects of micro-perforated film (MPF) packaging method on the quality and shelf life of pork loin during chilled storage were investigated, compared with non-packaging (control) and non-perforated film (PPF) packaging. Loins were removed from five hogs after slaughter and chilling, and each loin was portioned into four parts. These samples (40 sections) were allocated to each of five intervals (0, 1, 4, 7 and 14 days) to minimize variation among treatments and stored for 14 days under 55+/-10% relative humidity and 0+/-1 degrees C. Total aerobic counts of control sample were significantly lower than those from MPF or PPF loins after 14 days of storage. At 14 days, the counts of Pseudomonas and Enterobacteriaceae in the samples from MPF were significantly lower than those from PPF. At 7 days, 'L' value for the control and 'a' value for PPF were significantly lower, and DeltaE values for the control were significantly higher than other samples. During storage time, percentage weight loss was the most in the control samples with MPF following and PPF the least. Accordingly, water contents decreased highest in the control samples followed by those from MPF and PPF. TBA values increased with storage time, however no significant differences were observed among treatments. Sensory evaluation analyses showed that MPF samples were generally better evaluated in all parameters over the storage time. Therefore, it has been concluded that MPF could be used as an effective packaging technology since it extends the shelf life of fresh meat by controlling the microbial growth and evaporation at a moderate level. PMID- 22063935 TI - Comparison of antioxidant effects of milk mineral, butylated hydroxytoluene and sodium tripolyphosphate in raw and cooked ground pork. AB - The antioxidant effects of 0.5-2.0% milk mineral (MM) was tested in raw and cooked ground pork stored at 2 degrees C or -20 degrees C, compared to butylated hydroxytoluene (BHT) and sodium tripolyphosphate (STP). TBA numbers were low and not different between raw meat treatments. TBA numbers were lower (P<0.01) for cooked treatments with MM or STP compared to controls or treatments with BHT. Experiments were also done to determine acceptability of pork samples with various TBA values, and to determine effect of holding time before serving on TBA values. Cooked pork patties held at 71 degrees C for 90 or 120 min had higher (P<0.05) TBA values than patties held for 0-60 min. Thus patties could be warmed for 60 min after cooking without significantly increasing TBA number. For paired-preference sensory testing, patties were cooked and stored at 2 degrees C for 0, 1, 2 and 3 days to obtain TBA numbers of 0.4, 1.5, 3.4 and 3.9 respectively. Panelists preferred (P<0.001) patties with TBA number <0.5, compared to patties with TBA numbers >1.4. PMID- 22063936 TI - Effect of cooking temperature and cooking time on Warner-Bratzler tenderness measurement and collagen content in rabbit meat. AB - The effects of cooking temperature (50-90 degrees C) and time (10-120 min) on Warner-Bratzler (WB) tenderness measurement of longissimus lumborum (LL) muscle in 70-day-old rabbits were investigated. Cooking losses, total collagen content and collagen solubility of LL muscle were measured in parallel. Increasing cooking temperature caused a four-phase effect on WB measurement. Stress and total energy were significantly increased between raw meat and cooked meat at 50 degrees C, then they dramatically decreased to a minimum observed at 60-65 degrees C, and increased again to reach a maximum at 80-90 degrees C. Cooking losses exhibited an 83% increase between 50 and 80 degrees C. At 80 degrees C, stress and total energy values remained constant after 20 and 40 min respectively. LL muscle collagen content was 16.4+/-2.3 mg/g of dried muscle. Collagen solubility at 77 degrees C for 1 h was high: 75.3+/-8.1%. PMID- 22063937 TI - Influence of dietary conjugated linoleic acids (CLA) and age at slaughtering on meat quality and intramuscular collagen in rabbits. AB - To assess the effects of dietary conjugated linoleic acids (CLA) on meat composition and intramuscular collagen (IMC), 144 New Zealand White rabbits, half males half females, 55 days old (1.8 kg LW), were assigned to three weight- and sex- balanced groups and given the following dietary supplements: 0.5% sunflower oil, (C); 0.25% sunflower oil plus 0.25% CLA (T1); and 0.5% CLA (T2). The CLA was prepared from sunflower oil and contained 65% CLA isomers, half cis-9, trans-11 and half trans-10, cis-12. Six males and six females from each group (total 36) were slaughtered at 76, 90 and 104 days of age (corresponding to 2.5, 2.8, and 3.1 kg BW, respectively). The lean fraction was higher and the water content significantly higher in the meat of T2 compared to C and T1 for all ages combined. At the third slaughtering (104 days) the meat fat content was significantly lower in group T2. For all ages combined, IMC content, IMC hydroxylysylpyridinoline (HLP) concentration (index of collagen cross-linking) and IMC maturity (HLP/IMC) were significantly lower in the intermediate supplementation group (T1) compared to C and T2, and were also lower in animals slaughtered at 90 days. CLA supplementation has limited effects on the chemical composition of rabbit meat, with positive effects on meat texture and tenderness after supplementation up to 35 days at 0.25%, and a significant decrease in fat content only at high slaughter weight and high supplementation level (0.5%). PMID- 22063938 TI - Effect of added MU-calpain and post-mortem storage on the mechanical properties of bovine single muscle fibres extended to fracture. AB - The effects of MU-calpain and post-mortem storage on the strength of single muscle fibres were investigated. During the 10 min of incubation at pH 7.5, MU calpain became evenly distributed throughout the fibre. MU-Calpain-incubation resulted in thinner (P <0.001) Z-lines and reduced (P <0.001) the strength of the fibres compared to controls. These results demonstrate that MU-calpain is capable of mechanically weakening the muscle fibres. Post-mortem storage of meat for 10 days at 2 degrees C weakened (P <0.001) the muscle fibres compared to 24-h fibres. The presence or absence of Ca(2+) affected fibre stiffness. Fibres incubated at pH 7.5 in 100 MUM Ca(2+) were less stiff than fibres incubated in 200 MUM EGTA. Breaking stress and strain were not affected by Ca(2+). We hypothesise that Ca(2+) causes conformational changes in some of the load-bearing proteins, which alters their initial resistance to extension, but does not affect the breaking strength of the fibres. PMID- 22063939 TI - Sensory and meat quality traits of pork in relation to post-slaughter treatment and RN genotype. AB - The effects on eating quality and meat quality of two different forms of post slaughter treatment, performed in an abattoir, were studied in carriers and non carriers of the RN(-) allele. Carcasses were subjected to rapid and slow chilling, and pelvic and Achilles suspension in a factorial experimental design. A temperature of 10 degrees C was achieved in the centre of M. longissimus dorsi (LD) within 3.5 h in rapidly chilled carcasses and within 8 h in slowly chilled carcasses. In deep M. semimembranosus (SM) a temperature of 10 degrees C was achieved within 11.5 h in rapidly chilled carcasses and within 14 h in slowly chilled carcasses. LD from slowly chilled RN(-) carriers suspended by the pelvis exhibited the greatest tenderness, while LD from rapidly chilled non-carriers suspended from the Achilles tendon exhibited the lowest tenderness. Pelvic suspension or slow chilling of non-carriers produced the same improvement in tenderness, and when combined the tenderness increased further. However, the tenderness of the RN(-) carriers was already high, and no significant improvement was seen following any of the studied post-slaughter treatments. Pelvic suspension prevented shortening of muscle fibres, as seen by longer sarcomeres in LD from pelvic-suspended sides. However, longer sarcomeres were associated with greater tenderness only in LD from non-carriers of the RN(-) allele. The presence of the RN(-) allele and a slow chilling regime increased the rate of pH decline in LD. Achilles suspension also increased the rate of pH fall in SM, in addition to the RN(-) allele and slow chilling. The overall tenderness of LD was mainly related to the course of pH decline during rigor; lower pH values between 3 and 7 h post-mortem contributing to greater tenderness. The myofibrillar length was predominantly related to RN genotype and was shorter in RN(-) carriers than in non-carriers. The RN(-) allele and slow chilling contributed to higher evaporation losses and RN(-) carriers exhibited increased frequency of PSE meat in the ham muscles. The use of pelvic suspension appears advantageous over slower chilling, since it improved tenderness without any negative influence on drip loss, evaporation or cooking loss. PMID- 22063940 TI - Consumer perceptions: pork and pig production. Insights from France, England, Sweden and Denmark. AB - Consumer focus groups in France, England, Sweden and Denmark were used to obtain insights into the decision-making involved in the choice of fresh pork and attitudes towards today's pig production systems. Many positive perceptions of pork meat were evoked. Negative images of the production systems in use today were expressed, but rationalised in terms of consumer demands, market competition and by comparisons to previous systems of production. Knowledge of production systems appeared of little consequence in terms of any meat market potential as several groups freely remarked that there was no link between the negative images of production methods and their purchase behaviour. The groups were clearly confused and mistrusted the limited information available at the point of purchase. Careful consideration should be given to meat labelling, in particular taking account of the evident consumer ethnocentrism, to assure that such information is targeted to enhance consumer confidence. PMID- 22063941 TI - Carcass classification in suckling lambs. II. Comparison among subjective carcass classification methods: fatness scales and conformation scales with 0.25 point intervals. AB - Forty-nine Manchega breed suckling lambs were used. Carcass weight was less than 13 kg, and lambs were slaughtered at 10, 12 and 14 kg liveweight. Carcasses were classified by three assessors on colour photographs, by several classification methods: the European Union scale for light lambs carcasses (EU), Colomer-Rocher methods for fatness (CF) and conformation (CC), and the new scale for suckling lambs (SL) developed by our research group. Carcasses were also assessed using these scales divided into 0.25 point-intervals (EU-25, CF-25, CC-25 and SL-25). A correlation analysis was made between assessors score and tissue composition in the carcass and in three joints (leg, best end of neck and loin, and shoulder). For all the methods studied 0.25 point scales were best correlated to tissue composition than 1.0 points-interval scales. When 1.0 point-interval scales were used the SL scale was best correlated to tissue composition. When 0.25 point scales were used, the EU scale gave the best correlations. Conformation scale (CC) was useful to predict carcass composition, specially kidney knob and channel fat content. PMID- 22063942 TI - Quality of buffalo meat burger containing legume flours as binders. AB - The effect of addition of different decorticated legume flours, viz., soya bean, bengal gram, green gram and black gram, on the quality of buffalo meat burger was studied. The burgers consisted of optimized quantities of roasted or unroasted legume flour, spices and common salt. Inclusion of roasted black gram flour registered the highest yield of 95.7%, lowest shrinkage of 5% and lowest fat absorption of 26.6% on frying. Protein content of 18-20% was highest in the soya flour formulation. Free fatty acid (FFA) values (as% oleic) increased from 14.3 to 17.3 in freshly prepared samples (before frying) to 16.0-19.4 in 4 m frozen ( 16+/-2 degrees C) stored samples and fried samples had about 25% lower FFA values. Formulations with roasted flours registered lower thiobarbituric acid (TBA) values (mg malonaldehyde/kg sample) of 0.6-1.5 as against 0.6-2.1 for unroasted flours before frying. The burgers prepared with any of these binders were organoleptically acceptable even after storage at -16+/-2 degrees C for 4 months., However, the burger with black gram dhal (dehulled split legume) flour had better sensory quality attributes compared to other legumes. PMID- 22063943 TI - Use of Lactococcus lactis subsp. cremoris NCDO 763 and alpha-ketoglutarate to improve the sensory quality of dry fermented sausages. AB - The aim of the present work was to enhance the degradation of free amino acids in dry fermented sausages as precursors of volatile compounds responsible for the ripened flavour. For this purpose, Lactococcus lactis subsp. cremoris NCDO 763, its intracellular cell free extract (ICFE) and alpha-ketoglutarate were added to sausages. Papain was also used to increase the amount of free amino acids. When L. lactis was inoculated in sausages, an increase in the proteolytic phenomena was observed. The addition of alpha-ketoglutarate increased transamination phenomena in batches where it was added. The enhancement of these phenomena determined a noticeable rise in the content of glutamic acid (the main final product in transamination reactions) and a decrease, among other amino acids, of valine and leucine, with the formation of high amounts of their derivatives 2 methylpropanal and 3-methylbutanal. These aldehydes are responsible for the ripened flavour of dry fermented sausages. Sensory analysis showed an improvement of odour and flavour when L. lactis and alpha-ketoglutarate were combined. On the other hand, the intracellular cell free extract of L. lactis did not show any important activity in relation to amino acid breakdown even when used together with alpha-ketoglutarate and/or papain. PMID- 22063944 TI - Effects of liquid smoke on quality characteristics of Turkish standard smoked beef tongue. AB - The purpose of this research was to determine some quality characteristics of beef tongues processed with liquid and vaporous (traditional) smoke. The tongues were divided into two groups; traditional (vaporous) smoking and liquid smoke application groups, and the processed tongues were vacuum packaged and monitored for quality during 30 days of storage at 4+/-1 degrees C. All the smoked tongue samples were subjected to chemical, microbiological and organoleptic analysis at 0, 5, 10, 15 and 30 days of storage. The results indicated that despite some favorable results attributed to traditional smoking, liquid smoke application of beef tongue is also possible without causing any major acceptability problems in terms of quality. PMID- 22063945 TI - Ultra-fast freezing and low storage temperatures are not necessary to maintain the functional properties of manufacturing beef. AB - The effects of freezing rates and subsequent storage temperatures on the functional properties of meat were assessed. In the first trial, 24 Semitendinosus muscles were allocated to four freezing treatments to determine the effect of freezing rate alone (no frozen storage) on the functional properties of thawed muscle proteins. In the second trial, the effect of freezing rate, storage temperature and time were determined: 24 semimembranosus muscles were assigned to 30 treatment combinations using an incomplete factorial design with two freezing rates * three storage temperatures * five storage times. All samples individually sealed in water impermeable bags were thawed in water at 10 degrees C and then analysed. The rate of freezing alone in both trials and for both muscles had no effect on protein solubility; sulphydryl content; surface hydrophobicity; emulsion activity index or meat colour. Slowly frozen semimembranosus had more drip than fast frozen muscles. Semimembranosus muscle sarcoplasmic protein solubility increased and myofibrillar protein solubility decreased with storage temperature below -18 degrees C. Storage temperature did not affect the other attributes measured. Functional properties were mainly affected by storage time and the interaction between storage time and freezing rate. It is concluded that the current practice of blast freezing and storage at 18 to 20 degrees C is sufficient to maintain the quality of manufacturing beef. PMID- 22063946 TI - Effects of pork collagen on thermal and viscoelastic properties of purified porcine myofibrillar protein gels. AB - The objectives of this study were to examine the thermal, water-binding and viscoelastic properties of mixed protein systems containing purified myofibrils from porcine semimembranosus (MP) and pork collagen (PC) during gelation and subsequent cooling. MP:PC mixtures (100:0, 90:10, 80:20, 70:30, 60:40, 50:50) normalized to 4% protein were evaluated. No significant differences in thermal characteristics of these mixtures could be detected using differential scanning calorimetry. A primary peak was observed near 66 degrees C. Using small-strain oscillatory testing, the rheological properties during gelling and cooling were quantified. Storage modulus (G') increased upon heating for all treatments, but the rate of gel firming and the G' value at 85 degrees C were significantly lower (P<0.05) as PC was added to the mixed protein system. Upon cooling, gels revealed a significantly lower (P<0.05) rate of gel firming and significantly lower (P<0.05) G' value at 5 degrees C in samples with 20% inclusion of PC and higher. Addition of PC yielded a significant linear (R(2)=0.65; P<0.01) increase in the water-holding capacity (WHC) of the gels, indicating that the matrix formed in MP:PC gels had a greater ability to entrap water than that of the control MP gels. The inclusion of 10% PC resulted in gels with significantly higher (P<0.05) WHC and similar firmness when compared with gels comprised of MP as the only protein source. PMID- 22063947 TI - Sensory properties and lipid oxidation in aerobically refrigerated cooked ground goat meat. AB - Plain meat loaf and chili (a seasoned product) prepared with vacuum packaged/frozen-and-thawed ground goat meat were aerobically refrigerated for 0, 3, or 6 days. The 2-thiobarbituric acid-reactive substances (TBARS) content of the plain loaf increased ~3200 and ~4200% after 3 and 6 days, respectively, while peroxide value (PV) increased 250 and 430%. The corresponding increases for chili were much smaller (29 and 79% for TBARS and 90 and 47% for PV), most likely due to antioxidative effects of culinary non-meat ingredients used in chili preparation. Trained sensory panel evaluations of plain loaf samples showed that "cooked goat meat/brothy" aromatic (associated with freshly cooked goat meat) intensity decreased (P<0.05) 3% in plain loaf samples stored for 6 days, while "cardboard" aromatic (associated with oxidized cooked meat) intensity increased (P<0.05) 31%. "Cardboard" scores correlated (P<0.05) with both TBARS and PV, but the correlation was higher with TBARS. PMID- 22063948 TI - The effect of altered growth rates on the calpain proteolytic system and meat tenderness in cattle. AB - The present study was conducted to determine the effects of growth pattern on the calpain system and meat tenderization. Twenty-four Friesian calves were randomly allocated to three treatment groups: FAST (fast growth rate), SLOW (severely restricted growth rate) and ALTER (restricted growth for 30 days followed by fast growth rate). Four animals from each group were slaughtered on day 32 or 45 after altering the growth rates. Samples of M. longissimus dorsi were rapidly frozen at slaughter for protein analysis by Western blotting. Restricted growth reduced the immunoreactivity of a calpastatin band (135 kDa) measured at 24 h postmortem. Immunoreactivity associated with the large subunit of MU- or m-calpain appeared to be unaffected by growth patterns. Shear force measurements taken after 14 days of conditioning were positively related to 135 kDa calpastatin at 24 h postmortem. In this study there was no clear relationship between shear force and growth pattern. PMID- 22063949 TI - An evaluation of the growth, carcass and meat quality characteristics of Omani goat breeds. AB - Body weight, growth, carcass and meat quality characteristics were evaluated in three breeds of goats (Batina, Dhofari and Jabal Akdhar) in Oman. Fourteen intact male goats from each breed were used. Jabal Akdhar goats had significantly heavier slaughter, empty body, and carcass weights and higher growth rates than Dhofari and Batina goats. Jabal Akdhar goats had significantly heavier internal organs than the other two breeds. Dressing-out percent (based on empty body weight) of goats ranged between 53 and 57%, with the Dhofari goats having the highest value. Longissimus muscle dimensions varied between the three breeds, with Jabal Akdhar having a significantly larger area than Batina with Dhofari in between. Dhofari goats produced significantly shorter and wider carcasses than Batina and Jabal Akhdar goats. Carcass cuts were significantly heavier in Jabal Akdhar than the other two breeds. Four muscles (Mm. longissimus dorsi, biceps femoris, semitendinosus, and semimembranosus) from both sides of each carcass were subjected to two different ageing periods (1 day vs. 6 day) and evaluated for ultimate pH, expressed juice, percent cooking loss, colour (L*, a* and b*), and Warner-Bratzler shear force. Breed had a significant influence on pH and percent cooking loss but not on expressed juice, shear force value and colour (CIE L*,a*, b* values). Muscles from the Batina goats had significantly higher ultimate pH values and lower percent cooking loss than Dhofari and Jabal Akdhar goats. Ageing from 1 to 6 days increased tenderness significantly (27%), but decreased cooking loss by 5%. PMID- 22063950 TI - A fermented meat model system for studies of microbial aroma formation. AB - A fermented meat model system was developed, by which microbial formation of volatiles could be examined. The model was evaluated against dry, fermented sausages with respect to microbial growth, pH and volatile profiles. Fast and slowly acidified sausages and models were produced using the starter cultures Pediococcus pentosaceus and Staphylococcus xylosus. Volatiles were collected and analysed by dynamic headspace sampling and GC-MS. The analysis was primarily focused on volatiles arising from amino acid degradation and a total of 24 compounds, of which 19 were quantified, were used for multivariate data analysis. Growth of lactic acid bacteria was comparable for model and sausages, whereas survival of S. xylosus was better in the model. Multivariate analysis of volatiles showed that differences between fast and slowly acidified samples were identical for model and sausage. For both sausage and model, fast-acidified samples had a high content of ketones, sulphides and methyl-branched acids, whereas slowly acidified samples had the highest content of methyl-branched alcohols, aldehydes, their ethyl esters, phenylacetaldehyde and methional. Furthermore, model repeatability with respect to pH, microbial growth and volatile profiles was similar to sausage production. Based on these findings, the model system was considered valid for studies of aroma formation of meat cultures for fermented sausage. PMID- 22063951 TI - Effect of retail lights on acceptability of salami. AB - The effects of light source on the acceptability of Hungarian, Hot-Hungarian and regular salamis were investigated. The color of all salamis was most preferred (P<0.05) under incandescent (INC) light, as compared to fluorescent (FL) and metal halide (MH). Higher buying response was also evident when INC was used. The two Hungarian salamis, which had a high red component (higher a* and chroma values), received higher color preference scores under FL compared to MH. Most panelists described the color of the Hungarian salami under INC light as red, but brown under FL and MH. Relative luminance data, collected with a fiber optic probe connected to a photo-diode array, demonstrated the reason to be low red color seen in salamis presented under FL and MH lights. PMID- 22063952 TI - Comparison of clam-shell cookers and electric broilers and their effects on cooking traits and repeatability of Warner-Bratzler shear force values. AB - Clam-shell (CS) type cookers were investigated as an alternative cookery method for objective tenderness evaluations of beef strip loin steaks. This study was conducted in two phases: Phase I determined the most effective clam-shell cooking temperature setting (Low, Medium or High) and Phase II compared the repeatabilities of cooking traits and Warner-Bratzler shear (WBS) values from steaks cooked on electric broilers (EB) to steaks cooked on CS. Data from Phase I showed that cooking time was reduced (P<0.05) substantially for steaks cooked on CS with the shortest cooking times associated with the highest temperature settings. EB steaks had higher cooking losses compared with CS steaks (P<0.05), while the CS-Low temperature setting yielded the lowest cooking losses. WBS values did not differ except for steaks cooked on the CS-Medium setting, which were lower (P<0.05) than EB and CS-Low cooked steaks. CS-High setting was determined to be the optimum temperature setting for CS cooking because it required the least amount of time to cook and produced WBS values that were not different from steaks cooked on EB. Therefore, repeatability of cooking traits and WBS values of CS-High and EB were investigated in Phase II. Data from Phase II showed similar trends for cooking traits and WBS values between CS and EB cooked steaks as were observed in Phase I. Repeatabilities for WBS values were higher for steaks cooked on CS (R=0.86) compared with EB (R=0.41). The CS method appears to be an acceptable alternative to EB for cooking steaks used in meat tenderness research. PMID- 22063953 TI - Postmortem changes in myofibrillar-bound calpain 3 revealed by immunofluorescence microscopy. AB - An immunofluorescence microscopy method for following changes in myofibrillar bound calpain 3 was developed. Afterward, proteolytic changes in calpain 3(p94), calpain 1, titin, and nebulin were examined in myofibrils prepared from ovine longissimusthoracis et lumborum (LTL) stored for 0, 1, 2, and 3 days postmortem. Western blot analysis revealed that the levels of intact calpain 3 (expressed as percentage of the level immediately postmortem) were 80%, 10% and not detectable in myofibrils prepared at 1, 2, and 3 days, respectively. Western blots for calpain 1 also indicated conversion of the intact protein (80 kDa) to a 76 kDa fragment during the same time period. Thus calpains 1 and 3 appear to be activated during postmortem storage. Immunofluorescence microscopy using an IS1 region specific antibody revealed that calpain 3 staining was most intense at the sarcomere Z- and M-lines. The fluorescence intensity declined significantly during storage, paralleling changes in the proteolytic breakdown of titin and nebulin associated with these structures. PMID- 22063954 TI - Intramuscular variation in beef tenderness. AB - Intramuscular variation of beef tenderness was investigated in three muscles: Semitendinosus (ST), Triceps brachii (TB) and Rectus femoris (RF). The aim of the study was to evaluate a French process (called "affranchi") used to improve meat tenderness. Two groups of 72 muscles (24 ST, 24 TB and 24 RF) aged 10 and 14 days respectively, were assessed for tenderness by sensory analysis and compression measurements. For all three muscles, sensory evaluation showed a significant intramuscular variation in tenderness with a longitudinal gradient. Compression measurements on the raw meat showed similar results but of reduced accuracy. It appears that the process "affranchi" which consists in removing a part of the muscle, is very useful to improve meat tenderness and could be used by meat processors. The low relationship between compression measurements and sensory evaluation suggest compression measurements on raw meat are not suitable to predict meat tenderness as perceived by consumers. PMID- 22063955 TI - Effect of replacing beef fat with olive oil on quality characteristics of Turkish soudjouk (sucuk). AB - Four formulation of Turkish soudjouks were produced in three replicates by traditional methods as follows; one control (C) using 85% beef and 15% beef fat and three treatments by replacing 20, 40 and 60% of beef fat with virgin olive oil incorporated as pre-emulsified fat (PEF) with soy protein isolate (SPI), respectively. It was found that the moisture content and pH decreased while fat and ash content increased on the 21st day of fermentation and in the ripening period. Cholesterol content decreased depending on the amount of incorporated olive oil to the formulation, which shows the addition of olive oil in soudjouks reduces the cholesterol content (P<0.05). TBA values were affected by the amount of incorporated olive oil and the highest TBA value was found for with the 60% olive oil replacement. Oleic and linoleic acid contents were high while other fatty acid contents were low for the 40 and 60% olive oil samples compared with controls. Sausages with 40% olive oil received high evaluation from the panel for appearance and texture but there was no significant difference (P>0.05) between samples in the terms of color and general acceptability. It is concluded that replacement of beef fat with olive oil had a positive effect on sensory quality and on reducing the cholesterol content of soudjouks. PMID- 22063956 TI - Irradiation effects on meat flavor: A review. AB - Irradiating fresh meat, even at low doses, can result in off-odors and flavors which have been described as rotten egg, bloody, fishy, barbecued corn, burnt, sulfur, metallic, alcohol or acetic acid. The odors vary with the type of meat, temperature during irradiation, oxygen exposure during and/or after the irradiation process, packaging and presence of antioxidative substances. Irradiation can induce formation of isooctane-soluble carbonyl compounds in the lipid fraction and low molecular weight, acid-soluble carbonyls in the protein fraction of meat. Increasing irradiation dose increases these compounds however, cooking reduces them. Among the volatile components, 1-heptene and 1-nonene are influenced most by irradiation dose, and aldehydes (propanal, pentanal, hexanal) are influenced most by packaging type (aerobic vs vacuum). Sulfur-containing volatiles formed from sulfur-containing compounds (primarily amino acids) also contribute to irradiation odor. Dimethyltrisulfide is one of the most potent off odor compounds, contributing fishy, putrid odors, followed by bismethylthiomethane (sulfurous). Reducing the temperature during the irradiation process reduces the effects on odor/flavor because free radical generation and dispersion are reduced. Ultimately, radiolysis of water into free radical species (OH,H, H(3)0(+), e(aq)(-)) may be the initiators of both lipid oxidation breakdown products and sulfur-containing volatiles responsible for irradiation odor. Methods to decrease the detrimental effects of irradiation include oxygen exclusion (vacuum packaging), replacement with inert gases (nitrogen), addition of protective agents (antioxidants), and post-irradiation storage to allow flavor to return to near-normal levels (re-packaging or double packaging in oxygen permeable film). PMID- 22063957 TI - Effects of dietary vitamin A restriction during finishing on color display life, lipid oxidation, and sensory traits of longissimus and triceps brachii steaks from early and traditionally weaned steers. AB - Our objective was to determine the effects of vitamin A restriction during finishing on color display life, lipid oxidation, and sensory traits of longissimus lumborum (LL) and triceps brachii (TB) steaks from early and traditionally weaned steers. Forty-eight steers weaned at either 137+/-26 days (EW) or 199+/-26 days (TW) were supplemented with either 15,400IU/kg dry matter of vitamin A (HA) or restricted to no supplemental vitamin A (LA) during finishing for 210 and 150 days, respectively. Both LL and TB steaks from the HA steers had the darkest (P<0.05) color scores after 3 days of retail display in PVC packaging at 2 degrees C, and the highest (P<0.05) thiobarbaturic acid reactive substances (TBARS) values. Instrumental a*, b*, and saturation index values were lowest (P<0.05) in LL steaks from the HA steers. Instrumental L* values were lower (P<0.05) on days 4-6 in TB steaks from TW steers fed LA than those from EW steers fed HA. No differences were found in Warner-Bratzler shear force values or sensory traits in either muscle. No supplemental vitamin A versus high levels of vitamin A inclusion in finishing diets has potential to increase color display life and reduce lipid oxidation, with no effects on meat palatability. PMID- 22063958 TI - Incision of the heart during meat inspection of fattening pigs - A risk-profile approach. AB - Meat inspection in the EU is based on Regulation (EC) 854/2004. Accordingly a risk based meat inspection should be implemented. In this paper, the incision of the heart in pig meat inspection is discussed with respect to efficacy. The incision especially can reveal the presence of endocarditis. Here, Erysipelothrixrhusiopathiae (E. rhusiopathiae) and/or Streptococcussuis (S. suis) are of particular concern. Both agents are regarded to be zoonotic agents. There is some evidence for infection of humans via an alimentary pathway. Hence, the occurrence of E. rhusiopathiae and S. suis is a concern of public health (PH) as well as veterinary public health (VPH). However, other measures, including on farm disease prevention and diagnosis, seem to be more important for food safety. It is concluded that the incision and inspection of the heart is not justifiable with respect to PH aspects. PMID- 22063959 TI - Colour of bovine subcutaneous adipose tissue: A review of contributory factors, associations with carcass and meat quality and its potential utility in authentication of dietary history. AB - The colour of bovine subcutaneous (sc) adipose tissue (carcass fat) depends on the age, gender and breed of cattle. Diet is the most important extrinsic factor but its influence depends on the duration of feeding. Cattle produced under extensive grass-based production systems generally have carcass fat which is more yellow than their intensively-reared, concentrate-fed counterparts and this is caused by carotenoids from green forage. Although yellow carcass fat is negatively regarded in many countries, evidence suggests it may be associated with a healthier fatty acid profile and antioxidant content in beef, synonymous with grass feeding. Nonetheless, management strategies to reduce fat colour of grass-fed cattle are sought after. Current research suggests that yellow colour of this tissue is reduced if pasture-fed cattle are converted to a grain-based diet, which results in accretion of adipose tissue and dilution of carotenoids. Colour changes may depend on the initial yellow colour, the carotene and utilisable energy in the finishing diet, the duration of finishing, the amount of fat accumulated during finishing and the rate of utilisation of carotene from body fat. Differences in nutritional strategies which cause differences in fatty acid composition may be reflected by differences in fat colour and carotenoid concentration. Fat colour and carotenoids are prominent among a panoply of measurements which can aid the authentication of the dietary history and thus to some extent, the origin of beef, although this potential utility is complicated by the simultaneous rather than discrete use of forages and concentrates in real production systems. PMID- 22063960 TI - The morphological detection of bone and cartilage particles in mechanically separated meat. AB - The calcium content of mechanically separated meat (MSM) is a common indicator of elevated bone contents due to the separation process, e.g. as applied in EU regulations. But a direct morphological proof of bone material is needed, especially to identify undeclared MSM additives to meat products. We present a new morphological method for the detection of both bone and cartilage particles, because elevated cartilage contents may be indicative of MSM additives also. The method is based on simultaneous staining with Alizarin Red and Alcian Blue. We investigated MSM, commercially produced from breast of veal, for elevated particle contents. In addition, we determined the rate of recovery for minced pork mixed with 0-5% bone or cartilage. The results show that staining with Alizarin Red and Alcian Blue is suited to the efficient and simultaneous detection of bone and cartilage material in meat mixtures. The morphological staining is simpler than previously applied methods. Preparations can be assessed macroscopically, and they can be quantified gravimetrically. Manual sorting and weighing of particles appears to underestimate MSM contents if particles are ground very finely. PMID- 22063961 TI - The Jarvis Beef Stunner: Effects of a prototype chest electrode. AB - The Jarvis Beef Stunner electrically induces a stun, cardiac arrest and spinal discharge in adult cattle by three consecutive cycles. Concerns over varying incidences of cardiac arrest and some meat quality problems prompted this study to investigate the effect of replacing the conventional brisket electrode (T1) with a prototype chest electrode, with (T2), and without (T3) spinal discharge in 287 animals in a commercial abattoir. Repositioning the electrode did not significantly affect electrical parameters in any of the cycles. All animals received a cardiac arrest as assessed by electrocardiogram. Most post-stun/kill responses were unaffected. No difference was found in the incidence of a broken femur between treatments, but haemorrhages in the sirloin were significantly reduced by the prototype electrode (left: 51.1% (T1) vs. 30.3% (T3); right: 57.6% (T1) vs. 36.4% (T3)). The chest electrode was therefore efficient at causing cardiac arrest, did not significantly affect post-stun/kill responses and reduced haemorrhaging in the high-value sirloin. PMID- 22063962 TI - Carcass characteristics, fatty acid composition, and meat quality of Criollo Argentino and Braford steers raised on forage in a semi-tropical region of Argentina. AB - The purpose of this study was to characterize and compare the carcass characteristics, cholesterol concentration, fatty acid composition of intramuscular fat and subcutaneous fat, and meat quality of Criollo Argentino and Braford steers reared in an extensive system, without supplementation, and slaughtered at approximately 400kg live weight. The Braford steers had greater (P<0.05) carcass weight, yield, conformation score, marbling degree, fat thickness and fatness score than Criollo Argentino steers. The tissue composition of the 10th rib was: 68.1% vs. 63.6% muscle, 23.9% vs. 20.4% bone and 8.2% vs. 16.3% fat for the Criollo Argentino and Braford breeds, respectively. The meat of Longissimus muscle from Braford steers was lighter, redder, yellower and more tender than that from Criollo Argentino steers. The meat of Longissimus muscle from Braford steers had a higher fat content, similar protein and ash contents and a lower (P?0.001) cholesterol concentration than that from Criollo Argentino steers. The subcutaneous depot was the most saturated, while the intramuscular fat had the most polyunsaturated fatty acids. Intramuscular fat showed the highest ?h fatty acids, and PUFA/SFA and n-6/n-3 ratios and for MUFA/SFA, 16:0/18:0 and h/H ratios were not significantly different between adipose tissue depots. The influence of breed on the fatty acid profile varies among adipose tissues. In general, both intramuscular fat and subcutaneous fat from Criollo steers contained more unsaturated fatty acids and less saturated fatty acids, than did fat from Braford steers. PMID- 22063963 TI - Comparison of acids on the induction of an Acid Tolerance Response in Salmonellatyphimurium, consequences for food safety. AB - Salmonellatyphimurium inactivation at pH 3.0 in Brain Heart Infusion (BHI) and Meat Extract (ME) was studied using stationary-phase cells grown in non-acidified BHI (pH 7.4) and ME (pH 6.6) and acidified BHI and ME at pH values of 6.4, 5.4 and 4.5 with acetic, ascorbic, citric, lactic, malic and hydrochloric acids. Cells grown in buffered BHI (pH 7.0) were used as non-acid adapted control cells. Acid adapted S. typhimurium cells obtained in both media (BHI and ME) were more resistant to extremely acidic conditions when ME was used as challenge medium, although the ability of S. typhimurium to survive extreme pH conditions also depended on growth medium and type of acidulant used. Acid adapted cells grown in BHI developed a higher Acid Tolerance Response (ATR) than those grown in ME. When cells were grown in acidified BHI, no bacterial inactivation was observed after three hours of acid challenge in ME. Furthermore, when cells were grown in acidified ME at pH values of 6.4 and 5.4, D-values obtained using ME as challenge medium were, respectively, 6-9 and 10-15 fold higher than those found when BHI was used as challenge medium. In all cases, the order of acids in inducing the ATR was citric>acetic>lactic>malic?hydrochloric>ascorbic. These findings represent a concern for food safety as the increase in the acid resistance of acid adapted cells could allow for S. typhimurium survival in the strong acidic environment of the gastrointestinal tract. PMID- 22063964 TI - Effect of carbon monoxide packaging and lactate enhancement on the color stability of beef steaks stored at 1 degrees C for 9 days. AB - Our objective was to assess the effects of lactate enhancement in combination with different packaging systems on beef longissimus lumborum and psoas major steak color. Strip loins and tenderloins (n=16) were assigned to one of four injection treatments (non-injected control, water-injected control, 1.25%, and 2.5% lactate in the finished product). Steaks were individually packaged in either vacuum, high-oxygen (80% O(2)/20% CO(2)), or 0.4% CO (30% CO(2)/69.6% N(2)) and stored for either 0, 5, or 9 days at 1 degrees C. The L(*) and a(*) values of both the longissimus and psoas responded similarly to lactate, which at 2.5% darkened steaks (P<0.05) packaged in all atmospheres and improved (P<0.05) the redness of steaks packaged in high-oxygen. Packaging steaks in CO did not counteract the darkening effects of lactate. Nevertheless, CO improved (P<0.05) color stability compared with high-oxygen packaging. PMID- 22063965 TI - Changes of physicochemical, microbiological, and textural properties during ripening of Italian low-acid sausages. Proteolysis, sensory and volatile profiles. AB - In this study low-acid sausages were studied to characterize their physicochemical, microbiological, and textural properties during ripening. The final a(w) was 0.87-0.88, whereas pH values stayed around their initial values during processing. Lactic acid bacteria increased very slowly in number and a small increase of Micrococcaceae was also noticed. Low-acid sausages showed low hardness and cohesiveness, and were easily distinguishable by sensory analysis from other industrial and artisan sausages. Under the conditions of the study, observed volatile compounds were mainly from spices and wine. The respective contribution of muscle and indigenous bacterial enzymes to proteolysis was determined by comparing changes in low-acid sausages to those containing an antibiotic-antimycotic mixture or sugar. A large part of the degradation of myofibrillar proteins appeared due to endogenous enzymes, although bacterial proteinases contributed to the degradation of these proteins. The role of microorganisms in proteolysis was more evident in the degradation of sarcoplasmic proteins. PMID- 22063966 TI - Expression of adipogenic transcription factors in adipose tissue of fattening Wagyu and Holstein steers. AB - In this experiment, we studied the effects of breed differences on the protein expression of adipogenic transcription factors, the C/EBP family (C/EBPalpha, C/EBPbeta-LAP, C/EBPbeta-LIP and C/EBPdelta) and PPARgamma, in the adipose tissues of Japanese Black (Wagyu) and Holstein steers from various anatomical sites (subcutaneous, intermuscular, and mesenteric) at different fattening periods (19 and 24 months of age). The expression of C/EBPbeta-LAP and C/EBPalpha in the mesenteric fat tissue of Wagyu at 19 months of age was significantly higher than that of Holstein. The expression of C/EBPdelta in the subcutaneous, intermuscular and mesenteric fat tissue of Wagyu at 19 months of age was significantly higher than that of Holstein. The plasma insulin concentrations of Wagyu steers at 19 months of age tended to be higher than those of Holstein. No significant differences in the expression of the adipogenic transcription factors and plasma insulin concentration were observed between the breeds at 24 months of age. These results suggest the existence of breed difference on the expression of the C/EBP family between fattening Wagyu and Holstein steers at 19 months of age, whereas breed difference might have disappeared before 24 months of age. PMID- 22063967 TI - Effect of grass silage and concentrate based finishing strategies on cull dairy cow performance, carcass and meat quality characteristics. AB - Sixty-eight spring calving Holstein-Friesian dairy cows on completion of lactation were randomly assigned to one of four dietary treatments. The experiment commenced on 17th December 2005 and was completed on 27th June 2006. Pre-experimental live weight and BCS were 605kg (s.d. 68.9) and 2.7 (s.d 0.28), respectively. The four treatments were: ad-lib grass silage (GS), GS+3kg concentrate (GS+3), GS+6kg concentrate (GS+6) and GS+9kg concentrate (GS+9). All cows were finished to a live weight>620kg and a BCS>3.5. Live animal, carcass and meat quality characteristics were measured. Mean (s.d.) total feed utilized was similar, at 1.5 (0.05) tonnes DM/cow across all treatments. There was a linear (P<0.001) increase in ADG (kg/day) for the first three dietary treatments, GS (0.71), GS+3 (0.91), GS+6 (1.14) with no additional response to the final increment, GS+9 (1.15). As concentrate proportion in the diet increased there was a linear decrease (P<0.001) in days to slaughter. Cows on the GS+9 treatment (84 days) finished on average 12, 25 and 38 days earlier than those on the GS+6, GS+3, and GS treatments. The GS+9 treatment had lower carcass fat yellowness ('b' value) than the GS treatment but the GS+3 and GS+6 treatments did not differ from either GS or GS+9. There was no effect of treatment (P>0.05) on muscle redness ('a' value) following exposure to oxygen. When cull cows are finished to pre defined slaughter criteria, similar carcass classifications and carcass quality can be achieved with diets ranging from GS to GS+9, however significant difference in physical performance and days to slaughter will result. PMID- 22063968 TI - Prediction of fat, muscle and value in Norwegian lamb carcasses using EUROP classification, carcass shape and length measurements, visible light reflectance and computer tomography (CT). AB - One hundred and twenty carcasses were sampled to compare different techniques or methods for prediction of lamb carcass composition and value. Four methods that are used at the Norwegian Meat Research Centre, Animalia, were selected. These were the basic EUROP classification, the advanced EUROP classification using carcass shape and length measurements, visible light reflectance probing (GP) and Computer Tomography (CT). The different technologies were tested using an iterative approach, selecting calibration and validation data sets from the 120 carcasses randomly, where 90 carcasses were used for calibration, and 30 for validation. The best prediction models were obtained using CT, with respect to prediction error and correlation between predicted and measured value of carcass fat and muscle (in kg), and value (in NOK). Due to high cost and low operating speeds of CT, optical probing (GP) may be the second best solution of the technologies used in this study, combined with a CT dissection reference as an alternative to manual dissection. PMID- 22063969 TI - Histological characteristics of musculus longissimus dorsi and their correlation with restriction fragment length polymorphism of the myogenin gene in Jinghua*Pietrain F(2) crossbred pigs. AB - PCR-RFLP, periodic acid Schiff (PAS) and myosin heavy chain (MHC) immunohistochemistry were employed to survey the relationships between the genotypes of the myogenin gene (myog) and the histological characteristics of the muscle and other postmortem traits in the Jinghua*Pietrain (JP) F(2) crossbred pigs. The muscle fibers were classified into three groups according to their PAS reactivity: PAS(-), PAS(+~++), and PAS(+++) and accounted for approximately 16%, 74% and 10% of the total muscle, respectively. MHC immunohistochemistry was used to categorize muscle fibers into either slow or fast fibers; the proportions of slow and fast fibers were 6% and 94%, respectively. Two different cleavage patterns and three genotypes (AA, AB and BB) were identified and their frequencies were 0.4087, 0.4986 and 0.0928, respectively, for the three genotypes and 0.6580 and 0.3420, respectively, for cleavage patterns A and B. Different genotypes were variably associated with cross-sectional area (p=0.074), water holding capacity (p=0.002), pH (p<0.001) and carcass temperature (p<0.001) of the loin muscle. Different genotypes showed marked correlation with the L value (p<0.001), a value (p=0.002), and b (p<0.001) of the Minolta meat color index. The genotypes were also significantly related to the cross-sectional area (p<0.001), diameter (p<0.001), aspect ratio (p<0.001) and the density (p<0.001) of muscle fibers from the longissimus dorsi muscle. The results also revealed that the genotypes showed no significant association with the circularity (p=0.132) or the percentage of intramuscular connective tissue (p=0.193). PMID- 22063970 TI - Minerals, haem and non-haem iron contents of rhea meat. AB - Mineral contents, haem and non-haem iron of rhea (Rhea americana) muscles Obturatorius medialis (OM), Iliotibialis lateralis (IL) and Iliofibularis (I) were determined. No differences between the three muscles were observed for calcium, phosphorus, magnesium and sodium. There is more potassium, zinc and copper in IL muscle than in OM and I muscles. For Manganese, OM and IL muscles show a higher content in comparison with I muscle. For selenium, IL and I muscles show the highest content compared to OM muscle. For total, haem and non-haem iron, the IL muscle shows the highest content respect to the other muscles. When compared to other meats, the minerals content of rhea meat show an elevated level in phosphorus, selenium and total and haem iron. The human health concern due to the deficient diet in selenium and iron, and their high contents in rhea meat will be of great importance in the promotion of this meat. PMID- 22063971 TI - Dietary tannins improve lamb meat colour stability. AB - Fourteen male Comisana lambs were divided into two groups at 45days of age: lambs fed a concentrate diet (C), or lambs fed the same concentrate with the addition of quebracho (Schinopsis lorentzii) tannins (T). Sheep were slaughtered at 105days of age. Lipid oxidation, colour coordinates, haem pigment concentration, and metmyoglobin percentages were measured on minced semimembranosus muscle (SM) over 14days of refrigerated storage in a high oxygen modified atmosphere. Tannin supplementation increased (P<0.01) a(*) values and reduced (P<0.01) b(*) values of the SM when compared to C. Lower hue angles (P<0.001) and metmyoglobin formation (P=0.07) were observed in lamb from T-fed compared to C-fed sheep during the 14-days storage period. Furthermore, feeding T resulted in greater (P<0.001) haem pigment concentrations in the SM during refrigerated storage; however, diet had no (P=0.28) effect on lipid oxidation. Therefore, including quebracho tannins in sheep diets can improve meat colour stability of fresh lamb during extended refrigerated storage. PMID- 22063972 TI - Limousin myostatin F94L variant affects semitendinosus tenderness. AB - Texture parameters (peak force and compression), muscle myofibre diameter, and hydroxyproline were measured in semitendinosus samples from a cattle gene-mapping herd. The data were analysed to determine the relationships between these traits. The traits were also mapped by genetic linkage analysis to identify quantitative trait loci, and hence, candidate genes for these traits. Neither texture parameters were affected by the muscle structural traits of myofibre diameter or collagen content (as measured by hydroxyproline), despite significant variation in these traits between animals. QTL for the texture parameters of peak force and compression, as well as collagen content, were found on cattle chromosome 2 (BTA2) and attributed to the myostatin gene. Within the cattle population used for the QTL mapping, a gene variant of myostatin, F94L, has been previously shown to increase muscle mass, predominantly in the semitendinosus. It was determined herein that the F94L myostatin homozygous animals had more tender meat as measured by both peak force and compression. The variant was also responsible for a reduction in the collagen/elastin content of muscle. The myostatin F94L variant had no effect on muscle myofibre diameter of the semitendinosus, even though the variant causes substantial increases in muscle mass. Consequently, the increase in muscle mass of the variant must be due to myofibre hyperplasia and not hypertrophy. In addition, myostatin effects on tenderness are caused by changes in the extracellular matrix rather than muscle myofibre diameter. PMID- 22063973 TI - Colour calibration of a laboratory computer vision system for quality evaluation of pre-sliced hams. AB - Due to the high variability and complex colour distribution in meats and meat products, the colour signal calibration of any computer vision system used for colour quality evaluations, represents an essential condition for objective and consistent analyses. This paper compares two methods for CIE colour characterization using a computer vision system (CVS) based on digital photography; namely the polynomial transform procedure and the transform proposed by the sRGB standard. Also, it presents a procedure for evaluating the colour appearance and presence of pores and fat-connective tissue on pre-sliced hams made from pork, turkey and chicken. Our results showed high precision, in colour matching, for device characterization when the polynomial transform was used to match the CIE tristimulus values in comparison with the sRGB standard approach as indicated by their DeltaE(ab)(*) values. The [3*20] polynomial transfer matrix yielded a modelling accuracy averaging below 2.2 DeltaE(ab)(*) units. Using the sRGB transform, high variability was appreciated among the computed DeltaE(ab)(*) (8.8+/-4.2). The calibrated laboratory CVS, implemented with a low-cost digital camera, exhibited reproducible colour signals in a wide range of colours capable of pinpointing regions-of-interest and allowed the extraction of quantitative information from the overall ham slice surface with high accuracy. The extracted colour and morphological features showed potential for characterizing the appearance of ham slice surfaces. CVS is a tool that can objectively specify colour and appearance properties of non-uniformly coloured commercial ham slices. PMID- 22063974 TI - Meat quality and intramuscular fatty acid composition of Sanfratellano and Haflinger foals. AB - The goal of the trial was to evaluate meat quality, with an emphasis on intramuscular fatty acid composition, of Sanfratellano foals, compared to that from Haflinger foals,both slaughtered at 18 months of age. Thirty foals, half of Sanfratellano breed and half of Haflinger breed, naturally weaned at 7-8 months, were divided into two homogeneous groups at 15 months of age and fed a finishing diet based on polyphite hay and concentrate. The finishing period lasted three months. Sanfratellano foals showed higher slaughter weight (P<0.05) as well carcass weight (P<0.05) compared to Haflinger foals. Meat physical and proximate analyses did not discriminate the two groups. Normal pH values (5.6-5.7) measured at 4-6 day post mortem were recorded in meat from both groups. Shear force values accounted (range 55-58N) for a favourable tenderness in both groups. The intramuscular fat level was low in both groups (<2.5%) supporting the healthy image of this meat. The proportion of linolenic acid was higher (P<0.01) in Haflinger meat than in Sanfratellano one, thus causing a higher (P<0.05) total n 3 fatty acid content. Overall meat from both groups showed a favourable repartition among saturated (36-37% total FAME's), monounsaturated (33% total FAME's) and polyunsaturated fatty acids (30-31% total FAME's). PMID- 22063975 TI - The influence of cooking and fat trimming on the actual nutrient intake from meat. AB - The effects of cooking and trimming of visible fatty tissue on the content of fat, fatty acids, minerals and vitamins was studied in six meat cuts (beef rib eye and brisket, pork neck steak and belly, veal chop and rolled breast) in order to improve the estimates of the actual nutrient intake from meat. Cooking decreased the absolute fat content by about 17.9-44.4% and therefore concomitantly influenced the content of different fatty acids. The trimming of visible fatty tissue additionally decreased the fat content by about 23.8-59.1%. Calcium, sodium, potassium, magnesium and phosphorus decreased during cooking in all cuts and cooking processes, while iron and zinc were found to increase in beef. All vitamins decreased during cooking, with thiamine showing the highest losses, from 73% up to 100%. In conclusion, the cooking and trimming of meat cuts considerably affected the nutrients in various ways and to different degrees, which should be taken into account when the nutrient intakes of meat are estimated. PMID- 22063976 TI - Carcass and meat quality of Thai native cattle fattened on Guinea grass (Panicum maxima) or Guinea grass-legume (Stylosanthes guianensis) pastures. AB - Carcass and meat quality of Thai native cattle, fattened for 2 years on Guinea grass (Panicum maxima) and Guinea grass-legume (Stylosanthes guianensis) pastures, were investigated in twelve 3-years old males. Groups had similar carcass quality except for kidney fat percentage (higher in cattle of the grass legume group). This group also had a lighter meat (Longissimus dorsi, Infraspinatus) than the grass-only fed cattle. Shear force was generally at the borderline to tender meat, and was unaffected by treatment as were other texture related properties except muscle fibre diameter. Meat of the grass-legume group was perceived less juicy (P<0.05) but more tender (P<0.1). The meat of the grass legume-fed cattle also had more intramuscular fat (4.3% vs. 3.4%) and a slightly less favourable n-6:n-3 fatty acid ratio (2.2 vs. 2.0). In conclusion, the mostly weak differences in carcass and meat quality did not clearly favour one of the grazing systems. PMID- 22063977 TI - Compensatory growth response as a strategy to enhance tenderness in entire male and female pork M. longissimus thoracis. AB - The effects of restrictive feeding strategies aimed at promoting a compensatory growth response were investigated with respect to tenderness improvement in pork M. longissimus thoracis. Compensatory growth response is defined by increased weight in pigs fed ad libitum after a period with restricted feeding compared to pigs fed ad libitum the entire fattening period. Specifically, the aim was to study the sensory textural characteristics after female and entire male pigs have been exposed to restrictions in either energy, protein or both in specific growth periods. It was found that textural differences were caused by feeding strategies and not related to variation in intramuscular fat, which did not vary significantly between genders. The female pigs demonstrated compensatory growth response and the texture was significantly (P<0.001) improved by low dietary level of energy from day 50 to 90 and normal dietary level of protein during the entire feeding period. For the entire male pigs, low level of protein in the late feeding period significantly (P<0.05) improved the texture. Also, low level of protein and normal level of energy in the early feeding period resulted in improved tenderness. However, these texture improvements were deemed not to be an effect of compensatory growth since the entire male pigs did not compensate for the feeding restriction in the early feeding period. The tenderness enhancement for the entire male pigs compromised the production results in terms of 7-15% lower carcass weight. PMID- 22063978 TI - Effectiveness of combined preservation methods to extend the shelf life of Morcilla de Burgos. AB - Morcilla de Burgos is the most famous blood sausage in Spain. However, while producers are interested in extending its shelf life, the consumer is increasingly demanding more natural food. This situation has led to the current search for new and mild preservation technologies. Two batches of four different products: control without any treatment, control with organic acid salts (CnOAS; a 3% mixture of potassium/sodium l-lactate), control with high hydrostatic pressure processing (CnHPP; 600MPa-10min), and a combination of both treatments (OAS+HPP), were carried out to evaluate any synergistic effect that occurs when combining OAS and HPP, and the influence of different preservative treatments on the spoilage bacterial population and their evolution. HPP (with or without addition of OAS) can be considered the most suitable method for preserving morcilla de Burgos as it does not produce negative changes in sensory attributes. No clear selective effect of different treatments on the composition of the spoilage bacteria was seen and similar spoilage patterns were observed independently of the preservation treatment used. PMID- 22063979 TI - Effectiveness of poll stunning water buffalo with captive bolt guns. AB - Practical experience has indicated that shooting water buffalo with a captive bolt gun in the front of the head does not always produce an effective stun. Slaughtermen have been claiming that the poll position is more reliable, but under present EU regulations this shooting position is not allowed for domesticated bovines. This study examined the effectiveness of shooting water buffalo with captive bolt guns in the poll region. The depth of concussion was assessed in 30 water buffalo from physical collapse, presence or absence of corneal and palpebral reflexes, normal rhythmic breathing, eyeball rotation, nystagmus and whether the animal was re-shot. All except one animal collapsed immediately. The one animal that failed to collapse was not breathing. The prevalence of a shallow depth of concussion in the poll shot animals was 53%. Two had been shot through the spinal cord, and with the exception of those plus one other in which the bolt did not penetrate the brain, the other animals were considered to be adequately stunned. Post mortem examination of the brain showed that 79% of the under thirty month old animals were shot in the midbrain or brain stem, but these regions had to be avoided in over thirty month old animals because of the risk of damaging the brain stem sample needed for BSE testing. In addition, three water buffalo were shot in the crown position and one in the front of the head. The frontal position was ineffective as the animal did not collapse, and all animals shot in the crown position resumed breathing shortly after shooting, indicating a shallow depth of concussion. It is concluded that poll shooting can be effective in water buffalo, but it produces a shallow depth of concussion compared with frontal shooting in cattle. It requires accurate placement of the gun to ensure that buffalo are not shot through the spinal cord instead of the brain. Vigilance is needed in ensuring that the animals are stuck promptly so that none recover consciousness. PMID- 22063980 TI - CT scanning carcases has no detrimental effect on the colour stability of M. longissimus dorsi from beef and sheep. AB - This study investigated the effect of computerised tomography imaging (CT scan), for carcase composition determination, on the oxy/metmyoglobin ratio, hue and L(*), a(*) and b(*) scores of M. longissimus dorsi from both beef and lamb. Beef and lamb M. longissimus dorsi were divided into four proportions and randomly allocated to one of the following treatments; CT 30 day aged; CT fresh; control 30 day aged; control fresh. Colour measurements were made over a 96h retail display period. CT scan had little effect on the colour of both lamb and beef across all colour parameters. There was a small negative affect observed in CT aged samples (P<0.05) for ratio, hue, a(*) and b(*) values, however these differences were so small that they are unlikely to impact upon the commercial shelf-life of the product. Other factors such as aging, species and vitamin E concentration play a much greater role in colour stability than CT. Aged M. longissimus dorsi clearly had a worse colour stability than the fresh packaged samples, while beef was a lot more colour stable than lamb. It appears that CT scan for the purpose of body composition determination will not have any commercially relevant impact on colour stability of both beef and lamb. PMID- 22063981 TI - Alternating frequency to increase the response to stimulation from medium voltage electrical stimulation and the effect on objective meat quality. AB - The use of alternating frequencies during stimulation can increase stimulation response of a medium voltage electrical stimulation unit (MVS) by increasing the rate of pH decline. Various combinations of frequency modulation were tested in experiment 1 to determine the treatment resulting in the greatest stimulation response; the lowest initial pH, fastest rate of pH decline, highest temperature at pH 6 and the highest number of carcasses with a pH of 6 by 25(o)C and the treatment achieving the highest number of carcasses in the pH temp window (temperature at pH 6 between 18-25(o)C). The objective meat quality of these treatments compared to an unstimulated treatment was tested in experiment 2. Modulating the frequency (Hz) across the 6 segmented electrodes of the MVS by 10, 15, 25, 10, 15, 25Hz (Treatment 6, using a pulse width: 2.5ms, current: 1A) resulted in the greatest stimulation response. This treatment may be suitable for abattoirs that hot bone sheepmeat and require fast pH declines to ensure minimal cold shortening of meat. However, this treatment did not result in the tenderer meat despite the higher stimulation response. This treatment may have induced a greater number of contractions overall and therefore a greater pH decline response but resulted in less myofibrillar disruption compared to the other treatments due to a concomitant decreased force of contraction thus reducing potential tenderisation. Maintaining a constant frequency of 15Hz (Treatment 1; pulse width: 2.5ms, current: 1A) resulted in a higher number of carcasses in the pH temp window required (temperature at pH 6 between 18-25(o)C) in part A (P<0.05) and in addition to the higher tenderness levels this treatment may be more appropriate to satisfy the overall demands of abattoirs using these systems. This paper has also demonstrated electrical stimulation results in tenderer meat compared to unstimulated meat even after 30d of ageing (2.53+/-0.4 compared to 2.85+/-0.1 for the loin (M. longissimus thoracis et lumborum) (P<0.01) possibly due to a protective benefit of stimulation on meat tenderness. Overall, no detrimental effects of modulating frequency were observed on drip loss or retail colour display despite a greater rate of colour change observed with the modulated frequency treatment and the longer aged product. PMID- 22063982 TI - Acceptability of lamb fed on pasture, concentrate or combinations of both systems by European consumers. AB - It is well known that the eating quality of lamb is highly affected by feeding systems. The aim of this study was to ascertain acceptability of Uruguayan lamb meat from animals fed on different diets (only pasture-D1, only concentrate-D4 and two combinations of both systems-D3 and D4) by consumers from different European countries (Spain, Germany, United Kingdom and France). One hundred and twenty castrated Corriedale lambs were reared to 28.2+/-0.8 kg live weight and then thirty lambs were allocated to each diet and reared to 40kg live weight. Sections of loin were cooked using contact grills until the internal temperature of the muscle reached 72 degrees C (65 degrees C in France), cut and then served to consumers. A minimum of 180 consumers per country evaluated overall liking, flavour and tenderness acceptability of lamb from the 4 diets in sessions of 10 consumers using 8-point category scales. Globally consumers preferred lamb fed on concentrate or the combination of concentrate and pasture to lamb fed only on pasture. However, different segments of consumers were identified in each country based on their lamb acceptability. This information contributes to the identification of developing different commercial strategies in relation to the consumer segments found. PMID- 22063983 TI - Technological and safety properties of Lactobacillus plantarum strains isolated from a Tunisian traditional salted meat. AB - A total of 17 strains of Lactobacillus plantarum, isolated from a Tunisian traditional salted meat and identified by biochemical and molecular methods, were characterized according to their technological properties including acidifying, antimicrobial and enzymatic activities as well as antibiotic resistance in order to select the most suitable for use as starter cultures for the production of fermented sausages. All the strains studied showed good acidifying activity and were able to reduce the pH to less than 4.3 in 72, 48 and 24h at 15, 25 and 37 degrees C respectively. The majority of strains displayed antimicrobial activities against Salmonella arizonae, Staphylococcus aureus, Pseudomonas aeuroginosa and Escherichia coli, however characterization of the antimicrobial substances showed that none of the strains could produce bacteriocins. All the L. plantarum strains were able to hydrolyze casein, whereas none of them was found to possess lipolytic activity. The majority of strains of L. plantarum were resistant to tetracycline, erythromycin, rifampicin, ampicillin and penicillin G. PMID- 22063984 TI - Effect of crossbreeding and gender on meat quality and fatty acid composition in pork. AB - This study considers the effect of crossbreeding and gender (barrows; gilts) on meat quality and intramuscular and subcutaneous fatty acid composition in pork. The sire lines included Large White (LW), Duroc (D) and Pietrain (P) and the dam line was Landrace (LR)*LW, producing LW*(LR*LW), D*(LR*LW) and P*(LR*LW). Pork samples were removed from Longissimus dorsi (LD) and Semimembranosus (SM) muscles and subcutaneous fat (SCF). There were no important differences in meat quality parameters but D*(LR*LW) had the highest percentage of intramuscular fat. Castrated males had more intramuscular fat and more intense meat colour than female pigs. The Large White and Duroc sire line had saturated fatty acids (SFA) in SM, whereas the Pietrain sire line was significantly higher than Duroc sire line in the concentration of polyunsaturated fatty acids (PUFA), PUFA/SFA (P/S) and the n-6/n-3 ratio. The concentrations of SFA and monounsaturated fatty acids (MUFA) in SCF were significantly higher in LW*(LR*LW) and P*(LR*LW), respectively. No differences were found in the percentage of PUFA, P/S and n-6/n 3 ratio between D*(LR*LW) and P*(LR*LW). Female pigs had the most polyunsaturated intramuscular and subcutaneous fat. The results demonstrate small differences in fatty acid compositions among sires. PMID- 22063985 TI - Meat quality is associated with muscle metabolic status but not contractile myofiber type composition in premature pigs. AB - Longissimus muscles were sampled from Erhualian (EHL) and Pietrain (PIE) pigs at 20kg of body weight. No breed differences were detected in either the proportions or the mRNA/protein expression of respective MyHC isoforms, or the mRNA expression of PGC-1alpha (all P>0.10). However, meat quality traits were already divergent between breeds, and were associated with distinct energy metabolic status, as reflected by dramatically lower AMPK activity yet higher CK and LDH activities (all P<0.01) in longissimus muscle of EHL pigs. Moreover, mRNA expression of glucocorticoid receptor (GR) was found to be higher (P<0.05) in longissimus muscle of EHL pigs. These results indicate that the differences in meat quality traits occur early in premature pigs, and these are attributed to skeletal muscle energy metabolism and not contractile myofiber type composition. Breed-specific GR expression in muscle may be related to the pattern of energy metabolism and meat quality, yet the mechanism awaits further investigation. PMID- 22063986 TI - Cholesterol photosensitised oxidation of beef meat under standard and modified atmosphere at retail conditions. AB - The effect of the fluorescent light exposure and type of packaging (normal atmosphere and oxygen-rich atmosphere) was evaluated on the oxidation parameters (peroxides and cholesterol oxidation products) of raw beef slices placed in packed vessels and refrigerated. The concentration of COPs in meat treated under modified atmosphere ranged from 0.15 to 0.52mg/100g meat (average value of 0.27mg COPs/100g meat), which was twice as much as the average COPs content (0.14mg/100g) of meat packed under air (0.04-0.27mg COPs/100g meat). The main cholesterol oxide was 7k, which represented about one third of the total cholesterol oxides, followed by 7beta-OH (20-25% of total COPs), 7alpha-OH (about 20%) and beta-epoxy (12-18%). In normal atmosphere, photoxidation was a superficial process, since an inverse correlation between meat slice weight and COPs content on a lipid basis was observed, unlike in a high oxygen (32%) atmosphere. PMID- 22063987 TI - Detection of genetically modified organisms in processed meat products on the Serbian food market. AB - The addition of soybean proteins to processed meat products has significantly increased in recent years due to the interesting functional and nutritional properties of these vegetable proteins. Since the Roundup Ready (RR) soybean is the only transgenic soybean line approved for market in EU this work was aimed at monitoring its presence in meat products on the Serbian food market. The extracted DNA was analyzed using duplex polymerase chain reaction (PCR) with primer pairs aimed at the lectin gene and 35S promoter. Samples positive for the presence of GM soybean were subjected to a real-time quantification of the percentage of RR soya. The results indicated that out of fifty processed meat products examined, twelve gave positive results with 35S promoter and all contained RR soya below 0.1%. PMID- 22063988 TI - CO(2) stunning may compromise swine welfare compared with electrical stunning. AB - The effects of two different stunning methods on critical blood values in fattening pigs at a federal inspection slaughtering plant were monitored. A total of 658 pigs from the same genetic line and origin, were randomly assigned to 3 treatments: reference baseline levels (resting pigs; T1), stunning with CO(2) (T2) and stunned electrically (T3). Energetic profile, acid imbalance and blood gas levels, were monitored. Significant differences (p?0.05) between treatments for all variables were found, CO(2) stunned pigs showed hypercapnia, hypercalcemia, hyperglucemia, lactic acidemia, and an increase in haematocrit, coupled with reduced pH, [Formula: see text] , and Na; electrically stunned pigs had reduced blood pH, [Formula: see text] and [Formula: see text] . The remaining indicators were increased in relation to the resting swine. Thus CO(2) stunning leads to a major imbalance because of mineral and acid base gaseous interchange, compared to electric stunning, thus possibly compromising animal welfare. PMID- 22063989 TI - Use of pure glycerol in fattening heavy pigs. AB - Eighty Italian Duroc*Italian Large White pigs (BW 42.6+/-3.37kg) were used to determine the effects of pure glycerol on growth performance and meat quality of heavy pigs. Pigs were divided into five groups receiving 0% (control), 5% or 10% during the growing and finishing phases (42.6-160kg BW) (G+F5,G+F10) or 5% or 10% during the finishing period (100-160kg BW) (FIN5,FIN10) of pure glycerol in substitution for maize meal (on a dry matter basis). The pigs were slaughtered at approximately 160kg BW. The growth performance of pigs fed 5% glycerol did not differ from controls regardless of feeding duration, whereas those fed 10% glycerol showed reduced growth and poorer feed:gain ratio. Fat quality and meat suitability for raw ham curing were not affected by dietary treatment. Differences were not consistent enough to draw any conclusion about the effects of feeding glycerol on sensory characteristics. PMID- 22063990 TI - Phosphate analysis of natural sausage casings preserved in brines with phosphate additives as inactivating agent - Method validation. AB - Certain phosphates have been identified as suitable additives for the improvement of the microbial and mechanical properties of processed natural sausage casings. When mixed with NaCl (sodium chloride) and used under specific treatment and storage conditions, these phosphates are found to prevent the spread of foot-and mouth disease and classical swine fever via treated casings. The commercially available QuantichromTM phosphate assay kit has been evaluated as to whether it can serve as a reliable and low-tech method for routine analysis of casings treated with phosphate. The outcome of this study indicates that this particular assay kit has sufficient sensitivity to qualitatively determine the presence of phosphate in treated casings without interference of naturally occurring phosphate in salt used for brines in which casings are preserved. PMID- 22063991 TI - Effect of low temperatures (-18 to +5 degrees C) on the texture of beef lean. AB - The textural properties of beef over the temperature range -18 to +5 degrees C were measured using Warner Bratzler (WB) and tensile techniques. In addition, the effects of rapid radio frequency (RF) tempering and slower conventional air tempering on texture were compared. Temperature showed a significant effect (P<0.05) on WB and tensile shear force, with higher values obtained at temperatures on or below -5 degrees C. Work to fracture values showed two peaks at -15 and -3 degrees C. Sample thickness and muscle fibre direction were also important factors affecting shear force, with samples cut across fibres showing higher values. Tempering method showed no effect (P?0.05) on the textural properties measured. In light of the rapid nature of RF tempering, these findings will be of interest to the meat industry. PMID- 22063992 TI - Flavour development in pork. Influence of flavour precursor concentrations in longissimus dorsi from pigs with different raw meat qualities. AB - Flavour development and overall eating quality of pan-fried pork chops of longissimus dorsi from eight different raw meat qualities aged for 4 and 15 days were assessed by a trained sensory panel. The raw meat qualities were obtained through combinations of strategic feeding/fasting (control vs. low glycogen concentration), slaughter live-weight (84kg vs. 110kg), and gender (female vs. castrate). The flavour development was investigated for possible correlation with the concentrations of selected individual flavour precursors present in the raw meat: monosaccharides, IMP and degradation products, fatty acids, lactate and thiamine. Differences in precursor concentrations between the raw meat qualities were observed with feeding/fasting and ageing as the main factors with the largest influence of all experimental factors. However, the concentrations of the precursors could not explain the differences in sensory perception of the pan fried pork chops. Overall, the differences were small. PMID- 22063993 TI - New strategies for reducing the pork back-fat content in typical Italian salami. AB - In this work the possibility to substitute pork backfat with extra virgin olive oil (EVOO), adsorbed on whey protein-based crumb or white bread crumb, in typical Italian salami is addressed. Five types of salami were manufactured, under the usual commercial conditions, by replacing 0 (Control), 60% and 100% of pork backfat with whey protein-based crumb (WP60-WP100) and white pan bread (PB60 PB100), respectively, soaked in EVOO. Results highlighted that pH, weight loss, colour parameters and microbial counts did not show statistically significant differences between the Control and the modified salami. On the other hand, malonaldehyde was slightly lower in PB100, PB60, WP100 and WP60, compared to the Control. Chemical composition was significantly affected by formulations. Modified salami presented a better fatty acid profile showing lower saturated and higher monounsaturated fatty acids than control. Furthermore in all modified salami atherogenic and thrombogenic indices displayed the lowest values. The Control showed the highest values for Warner-Bratzler Shear, hardness, cohesiveness, gumminess and chewiness. Sensory evaluation of WP60 did not show significant differences compared to the Control, whereas PB100 and WP100 were unacceptable for taste. PMID- 22063994 TI - Compared development of intermuscular and subcutaneous fat in carcass and primal cuts of growing pigs from 30 to 140kg body weight. AB - A total of twenty two Large White X Landrace castrated males were slaughtered at 30, 70, 110 or 140kg BW. Carcasses were weighed and cut into four primal cuts (belly, ham, loin, and shoulder). Each cut was weighed and dissected into bone, muscle, skin, and intermuscular and subcutaneous adipose tissues. Kidney fat was also taken and weighed. Kidney fat grew more rapidly than subcutaneous or intermuscular fat averaged over all four cuts. In the shoulder and loin, about one third of total adipose tissue was in the intermuscular fraction. In the belly, there was as much (in 30-110kg BW pigs) or more (in 140kg BW pigs) intermuscular than subcutaneous adipose tissue. In the ham, the intermuscular fraction of adipose tissue grew more slowly than the subcutaneous one, so that it represented less than one fourth of total ham adipose tissue in 140kg BW pigs. Intermuscular adipose tissue exhibited a lower lipid content than subcutaneous adipose tissue, whatever the body weight, but the differences in lipid content between the adipose tissues decreased with increasing weight. These results show that the relative development of intermuscular and subcutaneous adipose tissues differs according to anatomical location. PMID- 22063995 TI - Optimisation of microwave assisted extraction (MAE) for polycyclic aromatic hydrocarbon (PAH) determination in smoked meat. AB - A rapid extraction method involving microwave assisted extraction (MAE), followed by sample clean-up on a silica cartridge, reversed-phase high performance liquid chromatography (RP-HPLC) and spectrofluorimetric detection, was optimised for polycyclic aromatic hydrocarbon (PAH) determination in smoked meat. Compared to solvent extraction assisted by sonication, MAE, carried out with n-hexane on 2g of lyophilised sample at 115 degrees C for 15min, allowed to obtain better extraction efficiencies. Limits of quantification (LOQ, s/n=10) lower than 0.2MUg/kg wet weight were found for all PAHs, except for Fl (0.3MUg/kg), P (0.6MUg/kg) and IP (0.4MUg/kg). The optimised procedure, that presented good analytical performances (with recoveries ranging from 77% to 103%, and precision within 10% for most of the PAHs), was applied to determine PAH content in different smoked meat products from the Italian market. PMID- 22063996 TI - Partial replacement of nitrite by annatto as a colour additive in sausage. AB - For decreasing the use of nitrite in sausage in industrial conditions, annatto (Bixa orellana L.) powder (1% norbixin) was used in two different formulations of sausage (with 55% and 70% of meat) as a replacement for 20%, 40%, 60%, 80% and 100% nitrite. Then the qualitative characteristics of the samples such as colour (L(*), a(*) and b(*)), microbial contamination and sensory tests (flavour and odour) were compared with the control (without annatto and with 100% nitrite) after 2, 10, 20 and 30 days from production and under the refrigerated condition. The Statistical comparison showed that in both formulations of sausage, the sample containing 60% annatto was the best sample for its colour (for higher a(*) and lower b(*)); yet, this sample also did not show any significant differences from the control for microbial contamination and sensory properties. PMID- 22063997 TI - Dual X-ray absorptiometry accurately predicts carcass composition from live sheep and chemical composition of live and dead sheep. AB - Fifty merino wethers (liveweight range from 44 to 81kg, average of 58.6kg) were lot fed for 42d and scanned through a dual X-ray absorptiometry (DXA) as both a live animal and whole carcass (carcass weight range from 15 to 32kg, average of 22.9kg) producing measures of total tissue, lean, fat and bone content. The carcasses were subsequently boned out into saleable cuts and the weights and yield of boned out muscle, fat and bone recorded. The relationship between chemical lean (protein+water) was highly correlated with DXA carcass lean (r(2)=0.90, RSD=0.674kg) and moderately with DXA live lean (r(2)=0.72, RSD=1.05kg). The relationship between the chemical fat was moderately correlated with DXA carcass fat (r(2)=0.86, RSD=0.42kg) and DXA live fat (r(2)=0.70, RSD=0.71kg). DXA carcass and live animal bone was not well correlated with chemical ash (both r(2)=0.38, RSD=0.3). DXA carcass lean was moderately well predicted from DXA live lean with the inclusion of bodyweight in the regression (r(2)=0.82, RSD=0.87kg). DXA carcass fat was well predicted from DXA live fat (r(2)=0.86, RSD=0.54kg). DXA carcass lean and DXA carcass fat with the inclusion of carcass weight in the regression significantly predicted boned out muscle (r(2)=0.97, RSD=0.32kg) and fat weight, respectively (r(2)=0.92, RSD=0.34kg). The use of DXA live lean and DXA live fat with the inclusion of bodyweight to predict boned out muscle (r(2)=0.83, RSD=0.75kg) and fat (r(2)=0.86, RSD=0.46kg) weight, respectively, was moderate. The use of DXA carcass and live lean and fat to predict boned out muscle and fat yield was not correlated as weight. The future for the DXA will exist in the determination of body composition in live animals and carcasses in research experiments but there is potential for the DXA to be used as an online carcass grading system. PMID- 22063998 TI - Brown tumour presenting as a soft-tissue mass. PMID- 22064000 TI - Myosin heavy chain isoforms account for variation in pork quality. AB - The objective of this study was to determine the impact of myosin heavy chain (MyHC) isoforms (I, IIB, IIA and IIX) on pork quality traits of halothane (HAL) negative (NN) and halothane-carrier (Nn) pigs. Gilts (n=32) were assigned to a 2*2 factorial of genetic population (GP) and slaughter weight (WT; 120 and 135 kg). Classical meat quality characteristics were collected and MyHC content was determined on muscle samples. Regression equations for pork quality and carcass composition traits were determined. Only I/IIB accounted for variation in drip loss of NN gilts (R(2)=0.18), while GP related to drip loss in Nn gilts (R(2)=0.70). Type I MyHC content explained variation in ultimate (24 h) muscle pH of NN gilts (R(2)=0.09), while I/IIB, I/IIX and IIB/IIX were significant for Nn gilts (R(2)=0.99). I/IIA, I/IIX, IIB/IIX and GP accounted for variation in Hunter Color a (redness) values of NN gilts (R(2)=0.69), while IIB, IIA, IIB/IIA and GP were significant for Nn gilts (R(2)=0.97). Overall, fiber type composition accounts for a larger proportion of variation in the quality traits of Nn compared to NN gilts. PMID- 22064001 TI - Sensory and chemical investigations on the effect of oven cooking on warmed-over flavour development in chicken meat. AB - Descriptive sensory profiling was carried out to evaluate the effect of oven cooking temperature (160, 170, 180, 190 degrees C) on warmed-over flavour (WOF) development in cooked, chill-stored (at 4 degrees C for 0, 1, 2 and 4 days) and reheated chicken patties, derived from M. pectoralis major. In addition, gas chromatography-mass spectrometry (GC-MS) was carried out on a representative sub set (160, 180, 190(o)C, stored at 4 degrees C for 0, 1, 4 days) of the meat samples used in sensory profiling. The effects of cooking and WOF in the sensory and chemical data were analysed using multivariate ANOVA-Partial Least Squares Regression (APLSR). Descriptive profiling indicated that WOF development was described by an increase of 'rancid' and 'sulphur/rubber' sensory notes and a concurrent decrease of chicken 'meaty' characteristics. Increasing cooking temperature resulted in meat samples with a more 'roasted', 'toasted' and 'bitter' sensory nature. Moreover, the 'roasted' character of the meat samples was also related to WOF development. Analysis of the volatile compounds from the chicken patties showed a rapid development of lipid oxidation derived compounds with chill-storage. Such compounds most likely contributed to the 'rancid' aspect of WOF development. Moreover, changes in sulphur-containing compounds were also related to WOF development and were proposed as additional participants in the lipid oxidation reactions. The sensory effects of these compounds were mainly described by the 'sulphur/rubber' note associated with WOF development. Overall, cooking temperature was found to increase the formation of Maillard-derived compounds, however, these did not appear to inhibit WOF development in the chicken patties. PMID- 22064002 TI - Analysis of biogenic amines in northern and southern European sausages and role of flora in amine production. AB - The biogenic amine contents, microbial counts and flora producing amines were investigated in four types of fermented sausages. Southern type European sausages (Italian and Belgian) showed higher tyramine and phenylethylamine values than northern type ones (Norwegian and Belgian). The spontaneous non-starter lactic acid bacteria could be responsible for the production of these amines in the Italian products, and the cocci Gram positive in the Belgian South ones. The Norwegian sausages showed the lowest total amine content of those studied. The two Belgian types were characterised by the highest putrescine contents, associated with high counts of Enterococcus. The production of amines in vitro by the starter cultures used in the manufacture of the sausages revealed that none of the Lactobacillus species produced any amines and only Kocuria varians and Staphylococcus carnosus showed phenylethylamine and tryptamine production. High correlations were found between the content of putrescine, histamine and cadaverine. PMID- 22064003 TI - Effects of starter cultures and additives on the quality of Turkish style sausage (sucuk). AB - The effects of starter cultures and additives on the quality of Turkish style sausage (sucuk) were investigated during ripening and storage. Total aerobic plate counts (aerobic bacteria), mould and yeast counts, pH, thiobarbituric acid (TBA) value and biogenic amine formation were followed. Aerobic bacteria increased (P<0.05) during the first 10 days of ripening to 9.26 log CFU/g and they decreased (P<0.05) to 5.70 at the end of the storage. Larger reductions (P<0.05) were observed in sausages made with high levels of potassium sorbate, nitrite and nitrate than in those containing low levels of additives and those without additives at the end of storage. During the first 3 days of ripening, the pH values of all sausages decreased (P<0.05) from 5.98 to about 4.53. Later, the pH values increased slowly, due to decomposition of acids to an approximately constant value of about 5.20. TBA values were higher (P<0.05) in the sausages made without additives than in the others. Sausages prepared using high concentration of additives had lower (P<0.05) concentrations of biogenic amines than the others. Addition of starter culture with high concentration of additives (nitrite, nitrate, alpha-tocopherol, ascorbic acid, potassium sorbate, potassium pyrophosphate and di-potassium hydrogenphosphate) decreased the formation of biogenic amine. PMID- 22064004 TI - Differentiation of the raw material of the Iberian pig meat industry based on the use of amplified fragment length polymorphism. AB - The present study is the first step of the development of a new analytical technique to discriminate the genotypes of purebred Iberian and crossbred Iberian*Duroc pigs. A DNA test of breed identity has clear advantages for the protection of the brand name of high-prized products of purebred Iberian pigs. Amplified fragment length polymorphism procedure was used to analyze the genomic DNA samples of 77 Duroc and 80 Iberian pigs from the most representative populations. Thirteen primer combinations produced 588 amplified fragments. A total number of 139 fragments were polymorphic and 14 out of them were detected in Duroc and never in Iberian pigs. A panel of the nine most frequent markers allows the discrimination between purebred and crossbred animals. The values of the probability of exclusion of the pure Iberian origin (P(EC)) were 0.97 and 0.78, for crossbred individuals with 50 or 25% of Duroc genes, respectively. PMID- 22064005 TI - Intron variability in an actin gene can be used to discriminate between chicken and turkey DNA. AB - A novel one-step method for the differentiation of chicken and turkey DNA is described. The technique uses the polymerase chain reaction (PCR) and primers that exploit intron variability in alpha-cardiac actin to generate single products of a characteristic size for each species. No cross-reactivity with porcine, ovine or bovine DNA templates is apparent and analysis of chicken/turkey admixtures indicates that it is possible to detect 1% turkey in 99% chicken and vice versa. Because the test is based on a nuclear gene target, it forms a valuable complement to other methods based on mitochondrial DNA sequences. PMID- 22064006 TI - Effect of calcium infusion on tenderness and ageing rate of pork m. longissimus thoracis et lumborum after accelerated boning. AB - The effect of calcium chloride infusion at either 0.5 or 6 h post slaughter on tenderness, ageing rate and meat quality of pork longissimus muscle that had been boned at rigor or had undergone accelerated processing and conditioning at either 0 degrees C or 14 degrees C was investigated. The time of calcium infusion had no effect on the initial WBSF values or the aging rate. However, calcium infusion overall resulted in lower WBSF initially (1-day post-mortem) and also after 6 days ageing at 2 degrees C regardless of the processing procedures used. Calcium infusion did not, however, increase the ageing rate compared to comparable treatments that had not been calcium infused. Based on this observation and the myofibrillar fragmentation index results, it was concluded that the increased tenderness due to calcium infusion was not due to increased proteolysis as has been previously postulated, but was due to either a direct effect of calcium on tenderness, or an indirect effect of calcium via increased post-mortem glycolysis and pH decline rate resulting in reduced cold shortening. Calcium infusion had detrimental effects on drip loss and meat colour. PMID- 22064007 TI - Consumer acceptability of dark, firm and dry (DFD) and normal pH beef steaks. AB - The sensory attributes of dark, firm and dry (DFD) and normal pH beef, both raw and fried, were evaluated and compared by a consumer panel (n=64). Consumer sensory evaluations indicated that the general appearance (P<0.05), colour (P<0.001) and acceptability (P<0.01) of raw normal pH steaks were preferred to those of raw DFD steaks. Twice as many panellists preferred the raw normal pH than raw DFD steaks because of the more attractive red colour, compared to the almost black colour of raw DFD steaks. No significant differences were found between the hedonic ratings of the sensory attributes of fried normal pH and fried DFD steaks. It was expected but not confirmed that consumers would find the tenderness of the DFD steaks more acceptable compared to the normal pH steaks. However, when forced to choose, female consumers significantly preferred fried normal pH steaks to fried DFD steaks, presumably because of a better flavour and more acceptable colour. PMID- 22064008 TI - Charqui meats as fermented meat products: role of bacteria for some sensorial properties development. AB - Jerked beef, a derivative of charqui meat, is a cured, salted and dried meat product. The presence of halotolerant bacteria, where Staphylococcus spp. (84.2%) were the predominant species, would act eventually as starter cultures and was followed throughout processing. Jerked beef prepared separately with exogenous S. carnosus and S. xylosus as starter cultures resulted in high proteolysis. Samples prepared with S. xylosus had the highest proteolysis and were preferred by the sensory panel. This research has suggested that jerked beef (and thus charqui meat) prepared under these conditions is a fermented meat product. PMID- 22064009 TI - Monitoring androstenone levels in boars by direct immunochemical analysis of serum samples. AB - The possibility of using blood samples for screening high levels of boar taint steroid androstenone (5alpha-androst-16-en-3-one) was studied both in living animals at the farm and carcasses at the slaughterhouse. The steroid was measured from boar serum and fat samples with a simple time-resolved fluoroimmunoassay. Fat samples contained androstenone in the range of 90-7500 ng/g (n=214), and 74.8% of the samples exhibited fat androstenone levels above 500 ng/g. Androstenone concentrations in blood samples were measured by direct serum assay and ranged up to 215 ng/ml (n=214). The levels of androstenone were correlated (r=0.78-0.88, P<0.001) between the serum and fat samples obtained at slaughter and serum samples taken at the farm 7-11 days before slaughter. A direct serum analysis seems to give a reliable indication of the androstenone level in fat and it can also be used in the screening of living animals. PMID- 22064010 TI - Changes in proteasome activity during postmortem aging of bovine muscle. AB - Changes in the chymotrypsin-like, trypsin-like, peptidylglutamylpeptide hydrolyzing and caseinolytic activities of proteasomes in bovine rectus abdominis muscle were measured during the first seven days of postmortem storage. Enzyme assays were performed in crude extracts under near-physiological conditions, since the activities are likely to be altered by purification. The different proteasome activities at cellular pH were stable at different times postmortem, and were 40, 76, 50 and 61% of their at-death value after 7 days of storage at 4 degrees C. This considerable postmortem stability of proteasome activities, despite the marked decrease in pH, allows them to play a role in meat tenderization in synergy with other proteolytic systems. PMID- 22064011 TI - Tenderness of pork m. longissimus thoracis et lumborum after accelerated boning. Part I. Effect of temperature conditioning. AB - This research investigated the effect on tenderness and meat quality of temperature conditioning at 0, 7, 14 or 21 degrees C of pork longissimus muscle after accelerated boning (removal from the carcass within 30 min post slaughter). The conditioning temperature had no effect (P>0.05) on tenderness at the end of the conditioning period (i.e. at the onset of rigor) but had a significant effect (P<0.05) after the muscles were aged for four days at 2 degrees C. After aging, the muscles conditioned at 14 degrees C were more tender than muscles conditioned at the other three temperatures; the muscles conditioned at 0 degrees C were tougher than the muscles conditioned at the higher three temperatures. Conditioning at 14 degrees C produced muscles that had lighter surface colour and lower drip loss due to prevention of cold toughening which occurred at lower temperatures or protein denaturation at the higher temperatures. PMID- 22064012 TI - Tenderness of pork m. longissimus thoracis et lumborum after accelerated boning. Part II. Effect of post-slaughter ageing. AB - This research investigated the effect of ageing time (0-10 days) at 2 degrees C on tenderness of pork longissimus muscle after either rigor boning (RB) or accelerated boning (removal from carcass within 30 min post slaughter) and temperature conditioning at either 0 or 14 degrees C. Ageing occurred most rapidly in muscles conditioned at 14 degrees C- maximum tenderization occurred by 4 days post-mortem. RB muscles and muscles conditioned at 0 degrees C aged more slowly and took 8 and 10 days, respectively, to reach a comparable level of tenderness. Temperature conditioning at 14 degrees C, produced muscles which had lower drip loss and lighter surface colour. PMID- 22064013 TI - Assessment for simulation learning outcomes: a comparison of knowledge and self reported confidence with observed clinical performance. AB - BACKGROUND: With extensive use of simulation in nursing education, researchers around the world are evaluating learning outcomes from simulation. Numerous studies reported the use of knowledge tests and self-reported measures to evaluate simulation outcomes. AIM: To determine whether self-reported confidence and knowledge measures are indicators of clinical performance observed in a simulation-based assessment. METHOD: Thirty-one third year nursing students were randomized into intervention and control group. The intervention group received a six hour simulation-based programme in care of a patient with physiological deterioration. Pre and post-tests using knowledge test, confidence scale and simulation-based assessment were conducted immediately before and after the simulation program. RESULTS: The intervention group had a significantly higher post-test mean score than the control group for knowledge and clinical performances. Both groups demonstrated a significant improvement on post-test scores from pre-test scores for self-confidence with no significant differences detected among the two groups. Correlation tests indicated no significant correlation between self-confidence and clinical performance, and between knowledge and clinical performance. CONCLUSION: The study did not provide evidence to support the validity of the knowledge test and self-confidence measures for predicting clinical performance. Most importantly, it revealed potential danger of a simulation-based assessment that could lead toward overestimation of self-confidence. PMID- 22064014 TI - Arcuate nucleus of hypothalamus is involved in mediating the satiety effect of electroacupuncture in obese rats. AB - Obesity is a major health problem in the world. Since effective remedies are rare, researchers are trying to discover new therapies for obesity, and acupuncture is among the most popular alternative approaches. This study investigated the anti-obesity mechanisms of EA, using a rat model of diet-induced obesity. After feeding with a high-fat diet for 9 weeks, a number of rats who gained weight that surpassed the maximal body weight of rats in the chow-fed group were considered obese and employed in the study. A 2 Hz EA treatment at the acupoints ST36/SP6 with the intensity increasing stepwise from 0.5-1-1.5 mA was given once a day for 30 min. Rats treated with EA showed significantly decreased food intake and reduced body weight compared with the rats in DIO and restraint group. EA treatment increased peptide levels of alpha-MSH and mRNA levels of its precursor POMC in the arcuate nuclear of hypothalamus (ARH) neurons. In addition, the cerebral spinal fluid (CSF) content of alpha-MSH was elevated by EA application. ARH lesions by monosodium glutamate abolished the inhibition effect of EA on food intake and body weight. A non-acupoint stimulation did not show the benefit effect on food intake inhibition and body weight reduction compared with restraint and ST36/SP6 EA treatment. We concluded that EA treatment at ST36/SP6 acted through ARH to significantly inhibit food intake and body weight gain when fed a high-fat diet and that the stimulation of alpha-MSH expression and release might be involved in the mechanism. PMID- 22064017 TI - "Nice guys finish last": influence of mate choice on reproductive success in Long Evans rats. AB - The present study was designed to determine if male physiology and male reproductive behavior predict reproductive success in Long-Evans rats. Mating behavior was observed in sexually naive, naturally cycling female rats during behavioral estrous that were given the opportunity to mate with two males simultaneously. DNA analysis of offspring born following these mating encounters was used to identify the paternity of each pup. In order to assess the effect of mate choice during these mating encounters on reproductive success, one male rat in each pair was categorized as the preferred mate if the female spent more time (>50%) with him during the mating test of the present study. Furthermore, each male in the pairs was categorized as "attractive" or "non-attractive" by computing the number of females that preferred each male across many mating tests. Similar to results reported in Lovell et al. (2007), during 76% of these mating tests the same male rat in each pair was preferred by different female rats. Overall attractiveness of individual male rats predicted reproductive success in the present study. Interestingly, "attractive" males sired significantly FEWER pups than "non-attractive" males. Neither behavioral (e.g., latency to first sexual stimulation, number of sexual stimulations) nor physiological measures (e.g., body weight, urinary testosterone levels) of male rats predicted their reproductive success. In conclusion, the present results indicate that certain features of some males are more attractive to females, but attractive males are at a reproductive disadvantage (as measured by the number of pups sired). Although basal urinary testosterone levels did not differ between males that sired the majority of pups in a litter and males that sired few or none of the pups in a litter, aggression and/or other physiological measures of fertility (e.g., penile reflexes) may differ between males that are attractive to females and those that have a reproductive advantage. PMID- 22064018 TI - Association of polymorphisms in the calpain I, calpain II and growth hormone genes with tenderness in bovine M. longissimus dorsi. AB - The objective of this study was to determine if there is an association between tenderness in bovine M. longisimus dorsi (LD) and polymorphisms in the bovine calpain I (exons 9 & 14), calpain II (regulatory subunit) or growth hormone (intron 3) genes. Genomic DNA was isolated from bovine LD (n=281) on which quality attributes (Warner Bratzler shear force (WBSF), sarcomere length and composition) were also characterised. DNA polymorphisms were analysed using polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. Association analyses were performed between genotypes at the four polymorphic loci and day 14 WBSF values. It was found that the calpain 1 exon 9 genotypes had an association with WBSF such that animals with the GA genotype exhibited decreased WBSF and increased tenderness when compared to animals with the GG genotype (P<0.05). This observation concurs with that of earlier studies, suggesting that this polymorphism is a functional marker for beef tenderness. PMID- 22064019 TI - Muscle type specific expression of tropomyosin isoforms in bovine skeletal muscles. AB - Nucleotide sequences encoding an entire coding region for bovine tropomyosin (TPM) isoforms were determined. Three TPM isoforms, TPM1, TPM2 and TPM3, were expressed in bovine skeletal muscles, and exhibited a 93.3%, 99.6% and 100% amino acid homology to the human sequence, respectively. Based on the sequences, the composition of TPM isoforms was analyzed on cDNA and protein levels from five physiologically different muscles (masseter, diaphragm, psoas major, longissimus thoracis and semitendinosus) using RT-PCR and proteome analyses. Although the content of TPM2 was constantly about 50% of the total TPM in all muscles, the contents of TPM1 and TPM3 were different in muscles according to their function in muscle contraction. In masseter, the content of TPM3 cDNA was about 50% and higher than that of other muscles. In longissimus thoracis and semitendinosus, the contents of TPM1 cDNA were 29.6% and 31.7%, respectively, which were comparatively higher than that of other muscles. The result suggests that the TPM dimer consists of the TPM2 subunit regularly and TPM1 or TPM3 depending on whether the muscle is fast or slow type, respectively. PMID- 22064020 TI - Effects of rigor temperature and electrical stimulation on venison quality. AB - The effects of rigor temperature and electrical stimulation on venison quality were assessed using venison longissimus dorsi muscle. In the first trial, effect of rigor temperature (0, 15, 25, 30, 35 and 42 degrees C) and time post-mortem (at rigor, 3, 7 and 14 days) on drip and cooking losses, % expressible water (water holding capacity, WHC), sarcomere length, protein solubility, meat tenderness and colour were investigated. In the second trial, the effects of rigor temperature (15 and 35 degrees C), electric stimulation (stimulated or not stimulated) and time (at rigor, 3 and 6 weeks post-mortem) on tenderness and colour were further investigated. Results of the first trial showed no clearly established trends of the effect of rigor temperature and time on the cooking and drip losses and protein solubility except venison muscles that went into rigor at 42 degrees C tended to have higher drip loss and lower protein solubilities compared to muscles that went into rigor at the other temperatures. Venison water holding capacity (WHC) decreased with the increase in rigor temperature (P<0.001) and venison became more tender with time post-mortem. Venison colour improved with increasing rigor temperature. During display, samples that went into rigor at 15, 25 and 35 degrees C had the lowest and those at 0 and 42 degrees C had the highest rate of change of redness (a(*)) value with time. In the second trial, tenderness was improved by stimulation (P=0.01). Redness (a(*)) values were affected by rigor temperature (P<0.01) and post-mortem time (P<0.001) but not by electrical stimulation. It is concluded that venison tenderness can be improved via the manipulation of rigor temperature to obtain acceptable level of tenderness early post-mortem with less damaging effect on colour stability. PMID- 22064021 TI - Lateral and longitudinal characterization of color stability, instrumental tenderness, and sensory characteristics in the beef semimembranosus. AB - The objectives of this study were to evaluate longitudinal and lateral variations in color stability and sensory characteristics of the semimembranosus from each muscle location (dorsal=D, medial=M, ventral=V), and within each steak subsequently divided into four regions (caudal-distal=CaD, cranial-distal=CrD, caudal-proximal=CaP, cranial-proximal=CrP). Instrumental color assessment indicated that L(*) (lightness) values tended to be lower for the CaD and CrD regions of all muscle locations, with higher L(*) values recorded for the CrP regions of muscle sections. Instrumental tenderness measurements for Meullenet Owens razor and Warner-Bratzler shear force values were generally lower for the CaD region of the D section, whereas regions within the V section were tougher and required greater shear force. Sensory panelists perceived lower amounts of connective tissue in the CaD of the D section, which tended to be more tender, whereas higher levels of connective tissue and greater toughness occurred in the CaP and CrP regions of the M and V sections. These results provide a detailed muscle profile of the quality variation within the semimembranosus, and may be used to further enhance the fabrication and marketability of this beef subprimal cut. PMID- 22064022 TI - Effect of ripening time and rearing system on amino acid-related flavour compounds of Iberian ham. AB - The evolution of free amino acids and amino acid-derived volatile compounds during the ripening of Iberian ham from pigs reared in a Montanera system (outdoor-based, with acorn and pasture available) and a Pienso system (indoor based, with a high oleic acid concentrate) was studied. Ripening time influenced significantly all the free amino acids detected (p<0.05) except for threonine and tyrosine. The total free amino acid content increased significantly from day 120 to day 230 (drying stage) and then the concentration remained almost steady. This marked increase in the free amino acid content matched an increase in the amino acid-derived volatile compounds. The volatile compounds also increased after day 230. Conversely, rearing system had a weak effect on the free amino acid content and on the amino acid-derived volatile compounds. Only glutamic acid was significantly influenced (p=0.027), and a slight effect on proline and aspartic acid was found (p=0.051 and p=0.084, respectively), concentrations being larger in Montanera hams than in Pienso ones. With regard to the amino acid derived volatile compounds, only a significant influence of rearing system on acetaldehyde and on the coelution of 2,6-dimethylpyrazine+dihidro-2(3H)furanone was found. The small differences caused by rearing system confirm the great importance of concentrate formulation. PMID- 22064023 TI - Effects of massaging on hardness, rheological properties, and structure of four wild boar muscles of different fibre type content and age. AB - Histochemistry (percentage number of three type fibres and their cross-sectional area) and changes in hardness, rheological properties (elastic and viscous moduli), and structural elements (mean fibre cross-sectional area and thickness of endomysium) of four wild boar muscles of different ages: biceps femoris (BF), semimembranosus (SM), quadriceps femoris (QF), and longissimus (L) subjected to effective massaging for 1, 2, 3, and 4h were evaluated. BF, with the high percentage of type I fibres, higher mean fibre cross-sectional area, thicker endomysium as compared with QF, SM and L, was harder, more elastic, and more viscous than the other three muscles. Muscles of older boars were found to contain higher percentages of type I fibres, lower percentages of type IIB fibres, bigger muscle fibre cross-sectional areas, thicker endomysium and higher values of hardness than the same muscles of young boars, whereas the percentage of type IIA fibres was about the same in the muscles of both groups. No effect of age on rheological properties was found. Muscle massaging resulted in an increase in the mean fibre cross-sectional area, changes in thickness of the endomysium, reduction in hardness and viscous moduli as well as in the elastic moduli of the muscles studied. The lower the initial values of textural and structural parameters and percentage of type I fibres of a muscle were, the higher was the muscles susceptibility to massage. BF compared to SM, QF and L, of all the older boar muscles tested compared to those obtained from young boars were less susceptible to mechanical tenderization. PMID- 22064024 TI - Quality and shelf life evaluation of fermented sausages of buffalo meat with different levels of heart and fat. AB - Investigations were carried to study the effect of heart incorporation (0%, 15% and 20%) and increasing levels of fat (20% and 25%) on physicochemical (pH, moisture content and thiobarbituric acid, TBA number) and microbiological (total plate count and yeast and mold count) quality and shelf life of semi dry sausages of buffalo meat during refrigerated storage (4 degrees C). Different levels of fat significantly (p<0.05) increased the pH of the sausage samples. However different levels of heart incorporation did not significantly (p<0.05) affect pH, moisture content and TBA number of sausage samples. Fresh samples had pH, moisture content and TBA number in the range of 5.15-5.28, 42.4-47.4% and 0.073 0.134 respectively. Refrigerated storage significantly (p<0.05) increased TBA number of control samples while storage did not significantly (p<0.05) increase the TBA number of sodium ascorbate (SA) treated samples. Total plate counts of twelve sausage samples were f under the TFTC (too few to count) limit at the initial stage. Incorporation of different levels of heart and also increasing levels of fat did not significantly (p<0.05) increase the log TPC/g values. Yeast and molds were not detected in twelve samples of semi dry fermented sausages in their fresh condition. Storage revealed that there was a consistent decrease in pH, and moisture content. Refrigerated storage significantly (p<0.05) reduced both pH and moisture contents. TBA number and total plate counts and yeast and mold counts of controls were found to increase significantly (p<0.05) during refrigerated storage. However, in SA treated sausage, only TPC and yeast and mold count significantly (p<0.05) increased during refrigerated storage. Shelf life of the sausages was found to be 60 days under refrigerated storage (4 degrees C). PMID- 22064025 TI - Regional variation in the hedonic evaluation of lamb meat from diverse production systems by consumers in six European countries. AB - This paper describes the responses of consumers in six European countries (Greece, Italy, Spain, France, Iceland and United Kingdom) tasting meat from twelve different local types of lambs produced in those same six countries. Animals represented 10 breeds and crossbreeds, three sexes, several diets composed of either milk, concentrates and various forages as main ingredients and different slaughter ages, from 1 and 12 months, and carcass weights, from 5.5 to 30.4kg. Tests were conducted by 36 volunteer families in each of the six countries involved in the study. Families were asked to roast the joints using their own cooking criteria, evaluating (from "dislike extremely" to "like extremely") flavour, tenderness, juiciness and overall liking. Also the cook was asked to rate the odour during cooking. Country and lamb type and their interaction were statistically significant for all the variables analysed. Results suggest a link between the assessments of a given lamb type and the consumers' culinary background, showing clear associations between country and lamb type preferences. It was possible to separate, independently of the country, different groups of families with similar preferences. Five family groups, which included 88 families (40.74%), had a clear Mediterranean origin and preferred types of lamb fed either milk or mainly concentrate diets. Seven family groups, which included 93 families (43.06%) with a clear northern origin, preferred types reared on grass or with grass included in the diet. The rest of the groups (four) that included 35 families (16.20%) had no clear composition (northern or Mediterranean), and they had a wider taste preference. It can clearly be seen that there are two categories of consumers of lamb in the analysed European market: those who prefer "milk or concentrate taste" and those who prefer "grass taste". PMID- 22064026 TI - Comparison of stunning methods in the dissemination of central nervous system tissue on the beef carcass surface. AB - Beef carcasses were examined to explore the effects of stunning methods on central nervous system tissue (CNST) dissemination on the surface during the slaughtering process. The frequency of occurrence of CNST contamination on four defined parts, each on the interior and exterior surfaces of the split carcass, and their level of the contamination were measured by an ELISA test. The effect of hot carcass weight was also examined. The results showed that the frequency of contamination occurrence was not affected by the stunning method. However, the penetrating captive bolt stunning method resulted in a higher level of CNST contamination than non-penetrating sledge-hammer stunning (P<0.001). The higher level of contamination occurred on the interior surface of carcasses along the vertebral area. Therefore, the dissemination of CNST on carcasses seemed to be affected by the stunning method, carcass splitting, and carcass washing. The carcass weight significantly affected the level of CNST contamination on the carcass (P<0.01) but there was no interaction with the stunning method. PMID- 22064027 TI - Effect of high power ultrasound and ageing on the physical properties of bovine Semitendinosus and Longissimus muscles. AB - Tenderness is an important meat quality parameters and the use of high power ultrasound to disrupt muscle structure may prove effective for reducing both myofibrillar and collagenous toughness. The experiment was carried out with Longissimus lumborum et thoracis and Semitendinosus muscles from 3 to 4 year old steers. Uncooked beef samples (60*40*20mm) were treated with high power ultrasound (24kHz, 12W/cm(2)) for up to 240s, and aged for up to 8.5 days before evaluation of pH, drip loss, cook losses Warner-Bratzler shear (WBS), compression hardness, and colour. Ultrasound treatment significantly reduced WBS force and hardness, but significantly increased pH. Ageing significantly reduced hardness and WBS force, but there was no significant interaction between ultrasound treatment and ageing time. Ultrasound treatment did not affect any of the colour parameters (L(*)a(*)b(*), chroma and hue) but the ageing time significantly increased the lightness, chroma and hue. There was no significant effect of ultrasound treatment on drip loss, but it did significantly reduce the cook and total loss. During ageing, cook loss and total losses significantly increased. The results suggest that high power ultrasound is capable of reducing objective texture measurements of beef without compromising the other quality parameters investigated. PMID- 22064028 TI - Influence of dietary inclusion level of manganese on pork quality during retail display. AB - Boneless pork loins (n=112) were used to test the influence of dietary manganese (Mn) inclusion level on pork quality traits during retail display. Crossbred barrows and gilts were fed diets formulated with 0, 20, 40, 80, 160, or 320ppm Mn from Availa((r))Mn (AvMn; a Mn-amino acid complex) from 23.8 to 106.8kg live weight. At approximately 48h postmortem, boneless pork loins were fabricated into longissimus thoracis et lumborum (LM) chops, which were subsequently placed in open-topped, coffin-chest display cases (2.6 degrees C) under continuous warm white, fluorescent lighting (1600lx) for 7days. Dietary Mn level had no effect on LM pH (P=0.47), purge volume (P=0.60) and loss (P=0.53), or moisture loss (P=0.95) during retail display. Chops from pigs fed 80ppm Mn received higher (P<0.05) American and Japanese color scores than pigs fed 0 and 40ppm Mn. Even though the LM from pigs fed 80, 160, and 320ppm Mn tended to be darker (lower L(*) values; P=0.07) than chops from pigs fed 40ppm Mn, a(*) (redness) and b(*) (yellowness) values, as well as hue angle and chroma, were not (P?0.19) affected by dietary Mn. On days 0 and 1, the reflectance ratio of 630nm/580nm was similar (P>0.05) among dietary Mn supplementation levels; yet, by day 4 of retail display, chops from pigs fed 80ppm Mn had higher (P<0.05) reflectance ratios than chops from pigs fed 0, 20, 40, and 160ppm, whereas LM chops from pigs fed 40ppm Mn had lower (P<0.05) reflectance ratios than all other dietary treatments on day 7 (Mn supplementation level*display day; P=0.04). Although TBARS were greater (P<0.001) on day 7 than 0 of retail display, TBARS values did not (P=0.43) differ among dietary Mn levels. Results indicate that supplementing swine diets with 80ppm Mn may improve pork color during retail display without increasing the likelihood of lipid oxidation. PMID- 22064029 TI - Effect of degree of cutting of leek on physicochemical characteristics of Greek traditional sausages. AB - Fresh-cut leek is one of the principal ingredients of Greek traditional sausages. In this study the effect of the degree of cutting of leek on the physicochemical traits of Greek traditional sausages was investigated. Leek was cut to three different degrees (coarse, medium and fine), before being mixed with meat, salt and seasonings; the mixture was placed in natural casings and stored for six days at 15-18 degrees C. Sausages lost about 25% of their initial weight by the end of storage. While pH decreased in all treatments, it was significantly more so (to pH 4.1) in sausages with fine-cut leek, from as early as the second day of storage. During storage all sausages showed a decrease in lightness and a change in colour from yellow to red. The internal atmosphere of the sausages with fine cut leek showed peak CO(2) concentrations of 30% while those with coarse and medium-cut leek showed peak CO(2) concentrations of 20% by day one of storage and equibrated to 5%. Ethylene in the internal atmosphere of sausages with fine and medium-cut leek peaked by day one at 5.5MUll(-1) but to only 2MUll(-1) for those with coarse-cut leek. Sausage nitrate content and antioxidant capacity did not show major differences between treatments. Fine-cut leek contributed to sausage stability and quality more rapidly than medium or coarse-cut leek. PMID- 22064030 TI - The effect of post-mortem ageing and heating on water retention in bovine muscles. AB - The muscles semitendinosus (ST) and psoas major (PM) were removed from chilled young bull carcasses 24h after slaughter and stored at 4 degrees C. At the 1st, 6th and 12th day of post-mortem ageing the chemical composition (moisture, fat, protein, collagen) and contents of free, immobilized and unfreezable water in the muscles were estimated. The muscle steaks were boiled at 100 degrees C, roasted at 170 degrees C or fried at 160 degrees C to an internal temperature of 75 degrees C, and the amounts of total, free, immobilized, and unfreezable water in heated muscles were evaluated. The unfreezable water was estimated by DSC. In the raw muscles immobilized water constituted 74-75%, free water 16.6-17.6% and unfreezable water 7-8% of the total water. Independent of time of ageing, PM muscle contained significantly more free water than ST muscle. During post-mortem ageing, changes in free, immobilized and unfreezable water in muscles were not significant. The level of free water was highest in boiled and least in fried meat, however the amount of immobilized water was highest in fried and lowest in boiled meat. The amount of unfreezable water in muscles heated after 12 days of post-mortem ageing decreased. PMID- 22064031 TI - Lipolysis, proteolysis, physicochemical and sensory characteristics of different types of Spanish ostrich salchichon. AB - The objective of this study was to compare three different types of salchichon: made of ostrich meat, made of ostrich meat and lean pork, and made of ostrich meat and pork belly, from physicochemical and sensory viewpoints. To evaluate the intensity of lipolysis and proteolysis produced during the ripening process, the profile and content of free fatty acids, the degree of rancidity, the non protein, water-soluble and aminoacidic nitrogen content were determined. In addition, the composition of the fermented sausages (pH, a(w), moisture, fat, protein, ash, sodium chloride and sodium nitrite content) was analysed. From a sensory viewpoint, the organoleptic characteristics of the different types of salchichon were studied using free choice profiling. The fermented sausages had varying characteristics depending on their formulation (ostrich meat or ostrich meat plus pork) and all of them were well accepted by the panelists. This study helps characterise the different types of ostrich salchichon made in Spain. PMID- 22064032 TI - Role of surface-inoculated Debaryomyces hansenii and Yarrowia lipolytica strains in dried fermented sausage manufacture. Part 2: Evaluation of their effects on sensory quality and biogenic amine content. AB - The aim was to study the effects of Debaryomyces hansenii and Yarrowia lipolytica strains, used with lactic acid starter cultures (Lactobacillus plantarum), in the manufacture of dried fermented sausages in order to understand their effects on volatile profile, biogenic amine content and sensory properties. The experimental data showed that every yeast strain produced a specific profile of volatile metabolic products. The yeasts also gave sausages with distinctive sensory properties. The degree of mincing also influenced these properties, but none of these factors had significant influence upon the accumulation of biogenic amines. PMID- 22064033 TI - Role of surface-inoculated Debaryomyces hansenii and Yarrowia lipolytica strains in dried fermented sausage manufacture. Part 1: Evaluation of their effects on microbial evolution, lipolytic and proteolytic patterns. AB - The aim of this work was to study the effects of Debaryomyces hansenii and Yarrowia lipolytica strains, used with lactic acid starter cultures (Lactobacillus plantarum), on the manufacture of dried fermented sausages to understand their role on sausage microbial evolution, lipolytic and proteolytic patterns. The inoculation of the yeast strains did not markedly affect the sausage's microbial flora. The sausages with the yeast strains showed more marked and earlier water activity (a(w)) reductions. Moreover, the surface inoculation of the yeast strains resulted, at the end of ripening, in more pronounced proteolysis and lipolysis. The lipolytic patterns of the products were affected not only by the yeast strain but also by the level of mincing of the meat mixture used. PMID- 22064034 TI - Aging-induced changes in microstructure and water distribution in fresh and cooked pork in relation to water-holding capacity and cooking loss - A combined confocal laser scanning microscopy (CLSM) and low-field nuclear magnetic resonance relaxation study. AB - Confocal laser scanning microscopy (CLSM) and low-field nuclear magnetic resonance (LF-NMR) relaxometry were combined to characterize microstructural changes and water distribution in fresh and cooked pork during an aging period of 14 days. At day 1 (24h postmortem) a few muscle fibres, which appear swollen, were observed in both fresh and cooked meat. An identical microstructure was still apparent after 14 days, however, the number of muscle fibres showing distinguished characteristics was found to increase throughout the aging period. Hence, it was apparent that during aging the individual fibres swell and disintegrate at different rates. Development in water-holding capacity (WHC) was followed during the aging period using gravimetric methods, and an increase in the WHC in the fresh meat was observed, which resembled the amount of extramyofibrillar water measured by NMR relaxometry (T(22) population). This was consistent with the CLSM images, as a substantial increase in the number of myofibrils that appeared swollen, capable of holding more water, was observed during aging. In the cooked meat the width of the T(21c) population, reflecting the myofibrillar water in the cooked meat, was seen to decrease during the entire storage period, which corresponds to the development of a more homogeneous structure. In the CLSM data a continuous degradation during the storage period was observed, which could resemble a shift to a more homogeneous structure. Comparison of CLSM of transverse sections of fresh and cooked pork revealed a pronounced shrinkage of muscle fibres upon cooking. This resulted in large gaps between the cooked muscle fibres, which also was visible as shrinkage at the level of the individual myofibrils. This pattern was also reflected in the NMR relaxation data. The cooking-induced shrinkage of the myofibrils occurred concomitantly with a decrease in the amount of intermyofibrillar water within the individual fibre and an increase in the larger extramyofibrillar spaces between fibres, i.e. water is expelled from the myofibrillar matrix upon cooking. Accordingly, the present study demonstrated that the use of CLSM together with NMR relaxometry can provide further information on the relationship between structural characteristics of meat and resultant water distribution. PMID- 22064035 TI - Characterization of Micrococcaceae isolated from Iberian dry-cured sausages. AB - The populations of Micrococcaceae in different types of Iberian dry-cured sausages from central-west Spain were characterized and their technological and antimicrobial properties determined in order to evaluate their suitability as starter cultures in dry-cured sausage manufacture. Of a total of four hundred strains isolated from two manufacturers, one hundred and sixty-six were selected to evaluate nitrate reductase, proteolytic, lipolytic, and antimicrobial activities, and growth at different values of pH and water activity (a(w)). Most of the strains were identified as Staphylococcus except for eight isolates assigned to Kocuria spp. The species most often isolated was Staphylococccus xylosus. Others were, in descending order of abundance, S. aureus, S. lugdunensis, S. saprophyticus, S. sciuri, S. chromogenes, and S. capitis. The distributions of the minority Staphylococcus species were different for the two manufacturers. All the investigated strains were able to grow at pH and a(w) greater than 5.0 and 0.85, respectively, the values usually found in Iberian dry cured sausages. Five S. xylosus strains showed antimicrobial activity against some indicator strains which were investigated. Seven strains with the best properties were pre-selected and tested for their lipolytic and proteolytic activities against pork fat and myofibrillar and sarcoplasmic pork proteins, respectively, and for their low biogenic amines production. Most of the strains showed proteolytic and lipolytic activities, but none produced histamine, tyramine, phenylethylamine, or spermine. Three strains, identified as Staphylococcus xylosus, possess useful properties which make them candidates for testing as starter cultures in pilot processing of Iberian sausages. PMID- 22064036 TI - Physical meat quality characteristics of hot-deboned ostrich (Struthio camelus var. domesticus) Muscularis gastrocnemius, pars interna during post-mortem aging. AB - There is a risk of shortening and toughening with hot-deboning of muscles. However, with refrigerated aging this phenomenon may be negated. Vacuum-packed hot and cold-deboned ostrich Muscularis gastrocnemius, pars interna were stored for 21 d at 4 degrees C to investigate the effects of hot-deboning on quality characteristics of ostrich meat during refrigerated storage. Muscle pH did not differ (P>0.05) between hot and cold-deboned muscles during storage. Hot-deboning caused (P<0.0001) more purge in the vacuum packages of the hot-deboned muscles (1.83+/-1.31%) than in the cold-deboned muscles (0.67+/-075%) during the 21-d aging period. Hot-deboned muscles were tougher (P<0.05) than cold-deboned muscles from 24h up to 5 d. Although hot-deboning caused muscles to be tougher than cold deboned muscles, with aging at 4 degrees C beyond 5 d this toughness was found to be insignificant. PMID- 22064037 TI - Novel method for determination of myofibril fragmentation post-mortem. AB - Multi angle light scattering was used to determine the myofibril fragmentation of pig longissimus dorsi muscle which was then compared with results from the common turbidity method. The method is based on measurement of the myofibril particle size distribution with the use of a special optical unit containing several individual detectors. The method was able to determine post-mortem changes in a pig muscle homogenate without purification of the myofibrils and is therefore simpler and much faster than the traditional turbidity method. There was a significant correlation (p<0.01) between Warner-Bratzler shear force (WBSF) and particle size distribution. The root mean square error of prediction was found to be 6.1N (10-15% of the measured WBSF) when multivariate data analysis was used to make a prediction model for WBSF. Multi angle light scattering is very useful for estimation of myofibril fragmentation since the method is fast and the sample preparation is simple. PMID- 22064038 TI - Genotype and sex effects on carcass and meat quality of suckling kids protected by the PGI "Cabrito de Barroso". AB - Carcass composition and meat quality traits were evaluated in 55 suckling kids (27 males and 28 females) from Serrana (S), Bravia (B) and Serrana*Bravia (S*B) crossbred genotypes. Kids were slaughtered at 8-11kg of live weight according to "Cabrito de Barroso-PGI" specifications and carcasses' left sides were totally dissected. Dressing percentage (based on ELW) did not vary between genotypes and sexes. Genotype B carcasses have better conformation, expressed in higher compactness index and muscle/bone ratio. Sex had no effect on the composition of dissected carcass but females deposited more internal fat than males. S genotype had significantly less muscle content and higher dissectible fat compared to B and S*B genotypes, suggesting differences in maturity stages. The carcass' bone content (20.4-21.4%) did not differ significantly between genotypes. The longissimus thoracis et lumborum (LTL) and gluteobiceps (GB) muscles were used for meat quality determinations. Genotype had a significant effect on meat traits and fatty acid composition of the analysed muscles: B genotype and LTL muscle showed lower final pH, S*B genotype had darker and more red muscles, GB muscle had a higher shear force value and lower collagen solubility. Few sex effects were observed on meat quality traits as well as on fatty acid composition. Average percentage of desirable fatty acids in kids was superior to 60% with male S genotype displaying a lower value. Genotypes B and B*S, males and GB muscle had more favorable PUFA:SFA ratios. PMID- 22064039 TI - Effect of grazing pastures of different botanical composition on antioxidant enzyme activities and oxidative stability of lamb meat. AB - The aim of this work was to study the influence of different pastures (Intensive ryegrass, Botanically diverse and Leguminosa rich pastures) on the antioxidant status and oxidative stability of meat from lambs that had been exclusively grazing for three months. Lipid, colour and protein oxidation, alpha-tocopherol content and activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (Cat) and glutathione peroxidase (GSH-Px)) were measured in Longisimus thoracis et lumborum muscle samples taken 1 day after slaughter. Pasture type significantly affected protein oxidation and the activity of GSH-Px, but no significant differences were found for the alpha-tocopherol content, colour and lipid oxidation, and the activities of SOD and Cat. Grazing a Botanically diverse pasture induced significantly higher protein oxidation in meat, as measured by the free thiol and carbonyl contents, compared to a Leguminosa rich or Intensive ryegrass pasture (P<0.05). The GSH-Px activity was significantly higher in meat from lambs on the Leguminosa rich pasture compared to the other pasture groups (P<0.01). PMID- 22064040 TI - Pigmented mammary Paget's disease mimicking melanoma: report of three cases. AB - Pigmented mammary Paget's disease (PMPD) is a rare subtype of mammary Paget's disease. The differential diagnosis of PMPD and melanoma is difficult clinically and sometimes histopathologically. Here we present three cases of PMPD with a variable-sized lesion. All cases showed an irregular-shaped black-brown macule, one of which was accompanied by nipple retraction. Dermoscopically, all cases showed reticular pigmentation with or without irregular black dots, regression structures and streaks, which were indistinguishable from those of melanoma. In all but one of the cases, preoperative examinations confirmed the presence of a subcutaneous mammary lesion. All patients underwent a total mastectomy with the histopathological results indicating invasive ductal carcinoma. These cases emphasize how difficult it is to distinguish PMPD from melanoma. Dermoscopic features also mimic those of melanoma, but the reticular pigmentation seen in all cases could be a feature specific to PMPD. For suspicious cases, histopathological assessment using immunohistochemistry is highly recommended. PMID- 22064041 TI - Conservative management of esophageal perforations during pneumatic dilation for idiopathic esophageal achalasia. AB - BACKGROUND & AIMS: Esophageal perforation is the most serious adverse event of pneumatic dilation (PD) for achalasia; it is usually managed by surgical repair. We investigated risk factors for esophageal perforation after PD and evaluated safety and long-term outcome of nonsurgical management strategies. METHODS: We analyzed medical records of patients with achalasia who were treated with PD from 1992-2010 at the University Hospital Gasthuisberg in Leuven, Belgium; all patients with esophageal perforation were contacted to determine long-term outcomes. Achalasia outcomes were assessed by using the Vantrappen criteria. RESULTS: Of 830 PD procedures performed on 372 patients with manometry-confirmed achalasia (57 +/- 1 years, 51% male), 16 were complicated by transmural esophageal perforation (4.3% of patients, 1.9% of dilations). Age >65 years was the only significant risk factor for complications (odds ratio, 3.5; 95% confidence interval, 1.2-10.2). All patients were treated conservatively with broad-spectrum antibiotics and nothing by mouth. In 6 patients (38%) the clinical course was further complicated by a pleural effusion, which required a drain in 4 patients. One patient (6%) died of mediastinal hemorrhage within 12 hours after PD. Patients with complications were discharged after 19 +/- 2.3 days, compared with 4 +/- 0.2 days for those without complications (P < .0001). Long-term outcomes (mean follow-up, 84 +/- 14 months) were determined for 12 patients (75%); 11 had excellent or good outcomes (69%), and 1 had a moderate outcome (6%). CONCLUSIONS: Age >65 years is a significant risk factor for esophageal perforation after PD. Nonsurgical management of transmural esophageal tears is feasible, with favorable short-term and long-term outcomes, but is not devoid of complications. PMID- 22064042 TI - Metachronous multiple clinical presentations in a patient with immunoglobulin G4 related sclerosing disease. PMID- 22064043 TI - Endoscopic examination of the stomach in situs inversus. PMID- 22064044 TI - Selective voting in convex-hull ensembles improves classification accuracy. AB - OBJECTIVE: Classification algorithms can be used to predict risks and responses of patients based on genomic and other high-dimensional data. While there is optimism for using these algorithms to improve the treatment of diseases, they have yet to demonstrate sufficient predictive ability for routine clinical practice. They generally classify all patients according to the same criteria, under an implicit assumption of population homogeneity. The objective here is to allow for population heterogeneity, possibly unrecognized, in order to increase classification accuracy and further the goal of tailoring therapies on an individualized basis. METHODS AND MATERIALS: A new selective-voting algorithm is developed in the context of a classifier ensemble of two-dimensional convex hulls of positive and negative training samples. Individual classifiers in the ensemble are allowed to vote on test samples only if those samples are located within or behind pruned convex hulls of training samples that define the classifiers. RESULTS: Validation of the new algorithm's increased accuracy is carried out using two publicly available datasets having cancer as the outcome variable and expression levels of thousands of genes as predictors. Selective voting leads to statistically significant increases in accuracy from 86.0% to 89.8% (p<0.001) and 63.2% to 67.8% (p<0.003) compared to the original algorithm. CONCLUSION: Selective voting by members of convex-hull classifier ensembles significantly increases classification accuracy compared to one-size-fits-all approaches. PMID- 22064045 TI - Implementation and evaluation of an education program to guide palliative care for people with motor neurone disease. AB - BACKGROUND: Despite a recognized need for a palliative approach to caring for people with motor neurone disease (MND), access to palliative care is often limited. AIM: This project aimed to improve the knowledge of health professionals about a palliative approach to MND care. DESIGN: A three-phase study was undertaken to develop, implement and evaluate an education program for health professionals that promoted a palliative approach to MND care. This paper discusses the second and third phases: the implementation and evaluation of the project. Education workshops were held for health professionals. Their knowledge of palliative care was measured before and after the workshops and one month later. Attitudes to providing MND care were also measured. SETTING: Workshops were held in South Australia and Western Australia. Participants were health professionals working in the areas of MND care or palliative care. Some aged care and generalist health professionals were included if they had a role in providing care to people with MND. RESULTS: The participants demonstrated an improvement in MND knowledge (chi(2) = 64.13(2), p = 0.000) and palliative care knowledge (chi(2) = 17.24(2), p = 0.000); both were sustained at one month. Attitudes to providing MND care also improved (chi(2) = 11.85(2), p = 0.003) and were maintained at the six-month follow-up. Participants indicated that the knowledge gained positively influenced their clinical practice. CONCLUSIONS: A targeted education program for health professionals improved understanding about end-of life care for people with MND. Health care providers also reported having made improvements in the care provided to patients and carers, particularly communication, psychosocial care and symptom management. PMID- 22064046 TI - Maternal quercetin intake during pregnancy results in an adapted iron homeostasis at adulthood. AB - The flavonoid quercetin is a powerful iron chelator, capable of oxidizing heme iron in hemoglobin from Fe(2+) to Fe(3+). Moreover, quercetin crosses the placenta and accumulates in the fetus. Since adaptations made by the fetus to cope with inappropriate nutrition may lead to permanent changes, a relative high intake of quercetin may have detrimental affects later in life. Therefore, we investigated the effects of maternal exposure to quercetin (302 mg/kg feed), starting from 3 days before conception until the end of gestation, on erythropoiesis and iron homeostasis at embryonic day 14.5 and in 12-week old mice. During fetal development, quercetin exposure had no effect on the erythroid lineage switch and concomitant globin switch. However, adult mice prenatally exposed to quercetin had significant increase iron storage in the liver, by upregulating iron-associated cytokine expression (hepcidin, IL-1beta, IL-6 and IL 10). These long term changes in gene expression could be mediated through epigenetic modifications, as prenatal quercetin exposure resulted in a modest hypermethylation of repetitive elements. Despite the increased iron levels, oxidative stress was significantly decreased in the liver of these animals as assessed by 8-oxo-dG levels. These data suggest that prenatal quercetin exposure results in increased iron storage, while decreasing oxidative stress induced DNA damage together with a shift towards increased expression of inflammation associated cytokines in the liver at adult age. PMID- 22064047 TI - 51st International Congress of Meat Science and Technology (51st ICoMST) Baltimore, USA, 7-12 August 2005. PMID- 22064048 TI - Epidemiology, risks and pathogenesis of obesity. AB - Obesity is operationally defined using a relationship of height and weight called the body mass index. Using this measure, more than 60% of Americans are overweight and over 30% are obese. To determine the importance of the body mass index, which would also label many athletes "overweight", we also need assessment of central fatness, and the medical conditions present in any given person. A problem of this magnitude is expensive, costing between 3% and 8% of health budgets in various countries. An increasing body weight increases the risk of early mortality, and enhances the risk of developing diabetes, gall bladder disease, high blood pressure, heart disease, osteoarthritis and certain forms of cancer. Although obesity results from an imbalance between what is eaten and what the body needs for its daily activities, these relationships are complex, and it is the "devil in the details" that is needed to provide clear public health strategies to prevent the progression of what some have called an epidemic. PMID- 22064049 TI - Effects of dietary factors and other metabolic modifiers on quality and nutritional value of meat. AB - A number of technologies that increase feed efficiency and lean tissue deposition while decreasing fat deposition have been developed in an effort to improve profitability of animal production. In general, the mode of action of these metabolic modifiers is to increase muscle deposition while often simultaneously reducing fat deposition. However, there have been some concerns that the focus on increasing production efficiency and lean meat yield has been to the detriment of meat quality. The aim of this review is to collate data on the effects of these metabolic modifiers on meat quality, and then discuss these overall effects. When data from the literature are collated and subject to meta-analyses it appears that conservative use of each of these technologies will result in a 5-10% (0.3 0.5kg) increase in shear force with a similar reduction in perception of tenderness. However, it should be borne in mind that the magnitude of these increases are similar to those observed with similar increases in carcass leanness obtained through other means (e.g. nutritional, genetic selection) and may be an inherent consequence of the production of leaner meat. To counter this, there are some other metabolic factors and dietary additives that offer some potential to improve meat quality (for example immuncastration) and it is possible that these can be used on their own or in conjunction with somatotropin, approved beta-agonists, anabolic implants and CLA to maintain or improve meat quality. PMID- 22064050 TI - Muscle profiling: Characterizing the muscles of the beef chuck and round. AB - To fully characterize properties of the muscles of the beef chuck and round, and to reveal potential opportunities to upgrade the value, 39 different muscles were dissected from 142 beef carcasses differing in carcass weight, yield grade, and quality grade. Numerous physical and chemical properties of the muscles were determined. Muscle effects were observed for all traits (objective color, expressible moisture, proximate composition, emulsion capacity, pH, total collagen content, total heme-iron concentration, and Warner-Bratzler shear force). USDA quality grade generally had the most effect on muscle traits, with carcass weight and yield grade having lesser effects. These muscle profile data will allow for more informed decisions to be made in the selection of individual muscles from the beef chuck and round for the production of value-added products. PMID- 22064051 TI - Enhancing palatability traits in beef chuck muscles. AB - Thirty-six USDA Select complexus, latissimus dorsi, rhomboideus, serratus ventralis (SEV), splenius, subscapularis, supraspinatus (SUS), and triceps brachii (TRB) muscles were studied. Muscles were assigned to one of four treatments: control, marinated, needle-pumped, and vacuum-tumbled to reach 10% brine pick-up after treatment. The solution was formulated to have 0.5% of sodium chloride and 0.4% of sodium tripolyphosphate in the end product. Steaks from the SEV, SUS, and TRB muscles were cooked on a grill and the other five muscles were oven-roasted whole, all of them cooked to an internal temperature of 71 degrees C. Sensory evaluations and Warner-Bratzler shear force (WBSF) determinations were conducted immediately after cooking (Day-1), and after being cooked and stored frozen for 60 days (Day-60). For the Day-60 evaluation, samples were reheated using a microwave oven. The needle-pumped treatment reduced WBSF values compared to the control in 3 out of 8 muscles (P<0.05). The marinated treatment appeared to have the greatest influence on juiciness and was different from the control in 7 of 8 muscles (P<0.05). Comparing treated muscles to the control, tenderness was increased in 4 out of 8 muscles when needle pumped (P<0.05). Brine treatment reduced sensory detected connective tissue only in 2 of 8 muscles. More off flavors were detected by the panel for marinated samples from six of eight muscles. All muscles had lower values for WBSF, less connective tissue and off flavors, and higher juiciness, overall tenderness, and beef flavor intensity on Day-1 than Day-60. The needle-pumped method was slightly superior to the marinated and vacuum-tumbled treatments even though the differences were not always consistent. But, regardless of the application method, palatability traits were generally enhanced by brine treatments. PMID- 22064052 TI - Use of comparative genomics as a tool to assess the clinical and public health significance of emerging Shiga toxin-producing Escherichia coli serotypes. AB - Shiga toxin (Stx)-producing Escherichia coli (STEC) cause sporadic or epidemic food- or water-borne illness whose clinical spectrum includes diarrhea, hemorrhagic colitis, and the potentially fatal hemolytic uremic syndrome (HUS). Over 200 STEC serotypes have now been implicated in human disease. Serotype O157:H7 is associated most outbreaks and most cases of HUS. Other serotypes are also associated with outbreaks and HUS but less commonly than serotype O157:H7, and some cause HUS but are typically non-epidemic. Many STEC serotypes have been associated with diarrhea, but not with outbreaks or HUS, while others, isolated from cattle, have never been linked to human disease. The only proven virulence strategies for STEC are Stx production and, in some strains, a characteristic attaching and effacing cytopathology on enterocyte that is mediated by factors encoded on a pathogenicity island (PAI) known as the locus of enterocyte effacement (LEE). But Stx subtypes and LEE cannot fully explain the apparent differences in virulence between STEC subgroups. However, publication of the genome sequences of two E. coli O157:H7 strains has revealed new candidate PAIs and has stimulated the use of novel approaches for assessing differences in virulence potential between groups of strains. This paper highlights the clinico pathological features and pathogenesis of STEC infection, new information arising from E. coli O157:H7 genome sequences, and progress in the use of of comparative genomics for assessing potential differences in virulence and public health significance between STEC subgroups. PMID- 22064053 TI - Pre-harvest interventions to reduce carriage of E. coli O157 by harvest-ready feedlot cattle. AB - Escherichia coli O157 is an important cause of food-borne illness. The primary reservoir for this organism is cattle and at present the major site of control is within abattoirs. Recent data have highlighted the importance of the pathogen load entering abattoirs on harvest-ready feedlot cattle. The likelihood for in plant intervention failure increases as the proportion of cattle carrying E. coli O157 within a pen increases. Pre-harvest reduction of E. coli O157 colonization will require targeted intervention strategies and should reduce contamination of carcasses thereby enhancing public health. Several pre-harvest interventions show substantial promise, such as specific strains of direct-fed microbials, vaccine technology, sodium chlorate, and neomycin sulfate, whereas others such as Brown Seaweed or chlorination of water have little or no detectable benefit. Selection of validated interventions strategies will be important as efforts to control pre harvest carriage of E. coli O157 increase. PMID- 22064054 TI - Post-harvest interventions to reduce/eliminate pathogens in beef. AB - In 1999 the foodborne pathogens Salmonella, Listeria, Campylobacter, and Escherichia coli (both O157 and non-O157) were estimated to cause more than 6 million illnesses and approximately 9000 deaths each year. However, the most recent Centers for Disease Control and Prevention report on the sources and incidence of foodborne disease, released in 2004, has shown a dramatic decrease in E. coli O157:H7 infections. Since raw beef products are the most frequently foodborne sources of these pathogens, the results of this report demonstrate that the microbiological quality of raw beef has improved greatly. During the intervening years, post-harvest interventions have continually improved, with new attention to hide decontamination and innovative treatments of carcasses. In addition, a system to hold and test beef trim or ground beef for E. coli O157:H7 before its release into commerce has provided an even greater level of safety. In this paper, we review the latest information on the prevalence of E. coli O157:H7 and other pathogens on beef, the evidence identifying the hide as the primary source of pathogens on beef carcasses, the efficacy of various hide and carcass interventions, and other developments that have led or have the potential to lead to even greater improvements in the microbial quality of beef. PMID- 22064055 TI - Viability of Listeria monocytogenes on commercially-prepared hams surface treated with acidic calcium sulfate and lauric arginate and stored at 4 degrees C. AB - We demonstrated the effectiveness of delivering an antimicrobial purge/fluid into shrink-wrap bags immediately prior to introducing the product and vacuum sealing, namely the "Sprayed Lethality In Container" (SLICTM) intervention delivery method. The pathogen was Listeria monocytogenes, the antimicrobials were acidic calcium sulfate (ACS; calcium sulfate plus lactic acid; 1:1 or 1:2 in dH(2)O) and lauric arginate (LAE; Ethyl-N-dodecanoyl-l-arginate hydrochloride; 5% or 10% in dH(2)O), and the product was commercially prepared "table brown" ham (ca. 3 pounds each). Hams were surface inoculated with a five-strain cocktail of L. monocytogenes (ca. 7.0 log(10) CFU per ham), added to shrink-wrap bags that already contained ACS or LAE, vacuum-sealed, and stored at 4 degrees C for 24h. Pathogen levels decreased by 1.2, 1.6, 2.4, and 3.1 log(10) CFU/ham and 0.7, 1.6, 2.2, and 2.6 log(10) CFU/ham in samples treated with 2, 4, 6, and 8mL of a 1:1 and 1:2 solution of ACS, respectively. In samples treated with 2, 4, 6, and 8mL of a 5% solution of LAE, pathogen levels decreased by 3.3, 6.5, 5.6, and 6.5 log(10) CFU/ham, whereas when treated with a 10% solution of LAE pathogen levels decreased ca. 6.5 log(10) CFU/ham for all application volumes tested. The efficacy of ACS and LAE were further evaluated in shelf-life studies wherein hams were surface inoculated with either ca. 3.0 or 7.0 log(10) CFU of L. monocytogenes, added to shrink-wrap bags that contained 0, 4, 6, or 8mL of either a 1:2 solution of ACS or a 5% solution of LAE, vacuum-sealed, and stored at 4 degrees C for 60 days. For hams inoculated with 7.0 log(10) CFU, L. monocytogenes levels decreased by ca.1.2, 1.5, and 2.0 log(10) CFU/ham and 5.1, 5.4, and 5.5 log(10) CFU/ham within 24h at 4 degrees C in samples treated with 4, 6, and 8mL of a 1:2 solution of ACS and a 5% solution of LAE, respectively, compared to control hams that were not treated with either antimicrobial. Thereafter, pathogen levels remained relatively unchanged (+/-1.0 log(10) CFU/ham ) after 60 days at 4 degrees C in hams treated with 4, 6, and 8mL of a 1:2 solution of ACS and increased by ca. 2.0-5.0 log(10) CFU/ham in samples treated with 4, 6, and 8mL of a 5% solution of LAE. For hams inoculated with 3.0 log(10) CFU, L. monocytogenes levels decreased by 1.3, 1.9, and 1.8 log(10) CFU/ham within 24h at 4 degrees C in samples treated with 4, 6, and 8mL of a 1:2 solution of ACS, respectively, compared to control hams that were not treated. Likewise, levels of the pathogen were reduced to below the limit of detection (i.e., 1.48 log(10) CFU/ham) in the presence of 4, 6, and 8mL of a 5% solution of LAE within 24h at 4 degrees C. After 60 days at 4 degrees C, pathogen levels remained relatively unchanged (+/-0.3 log(10) CFU/ham) in hams treated with 4, 6, and 8mL of a 1:2 solution of ACS. However, levels of L. monocytogenes increased by ca. 2.0 log(10) CFU/ham in samples treated with 4 and 6mL of a 5% LAE solution within 60 days but remained below the detection limit on samples treated with 8mL of this antimicrobial. These data confirmed that application via SLICTM of both ACS and LAE, at the concentrations and volumes used in this study, appreciably reduced levels of L. monocytogenes on the surface of hams within 24h at 4 degrees C and showed potential for controlling outgrowth of the pathogen over 60 days of refrigerated storage. PMID- 22064056 TI - Current research in meat color. AB - This review surveyed recent literature focused on factors that affect myoglobin chemistry, meat color, pigment redox stability, and methodology used to evaluate these properties. The appearance of meat and meat products is a complex topic involving animal genetics, ante- and postmortem conditions, fundamental muscle chemistry, and many factors related to meat processing, packaging, distribution, storage, display, and final preparation for consumption. These factors vary globally, but the variables that affect basic pigment chemistry are reasonably consistent between countries. Essential for maximizing meat color life is an understanding of the combined effects of two fundamental muscle traits, oxygen consumption and metmyoglobin reduction. In the antemortem sector of research, meat color is being related to genomic quantitative loci, numerous pre-harvest nutritional regimens, and housing and harvest environment. Our knowledge of postmortem chilling and pH effects, atmospheres used for packaging, antimicrobial interventions, and quality and safety of cooked color are now more clearly defined. The etiology of bone discoloration is now available. New color measurement methodology, especially digital imaging techniques, and improved modifications to existing methodology are now available. Nevertheless, unanswered questions regarding meat color remain. Meat scientists should continue to develop novel ways of improving muscle color and color stability while also focusing on the basic principles of myoglobin chemistry. PMID- 22064057 TI - New packaging technologies for the 21st century. AB - This paper reviews the major influencers that will drive change in meat packaging. A review of the current state of fresh-meat packaging in the US has shown a continued evolution to case ready packaging, with 60% of the packages audited being in the case ready format, versus 49% just two years earlier. Additionally, the market is moving to a higher degree of convenience in the meat case, and reducing the linear feet devoted to fresh meat (69% fresh meat linear feet two years ago, versus 63% in 2004). Additional evidence for the growth of convenience items was shown by a 48% growth in shelf stable meal kits between 1998 and 2003. Packaging innovations have been developed to meet these needs for convenience, but have largely been implemented outside of the meat industry. These include, but are not limited to, lines of hand-held soups, self-heating cans and cartons that are replacing the traditional steel can for retort purposes. The recent developments of films that are ovenable in traditional as well as microwave ovens are critical to the further advancement of convenience meat items. Material costs are also driving the need for packaging innovations. Polyethylene costs rose 20% during the second half of 2003, which is largely due to increased petroleum costs. As petroleum costs are sustained at the current high levels, renewable packaging for food, such as materials based on polylactide, will become more feasible. Labor costs and availability at retail will continue to drive the demand for case ready packaging innovations. The recent regulatory approval of carbon monoxide in fresh meat packaging in the US will enable greater usage of low oxygen packaging formats and should provide greater retail acceptance of case ready in the US. PMID- 22064058 TI - Functional genomics in farm animals - Microarray analysis. AB - The rapid progression of farm animal genomics has introduced novel technologies capable of presenting global descriptions of biological systems at the level of gene and protein expression and protein interaction. To fully benefit from these developments, experimental designs have to be adapted to these new technologies, and important considerations must be made in the choice of technologies and methods of analysis to be used. This paper addresses practical issues in the use of microarray based methods for gene-expression analysis in farm animals, and provides an overview of different array-platforms as well as a presentation of methods and software for the analysis of array data. Experimental design and the selection of animals and samples for microarray studies in farm animals present novel challenges, which are often overlooked. In particular, the frequent use of half sibs and full sibs in animal studies increases the risk of falsely identifying genes as being differentially expressed, due to genetic linkage of the gene to a QTL or a major gene affecting the trait in question. PMID- 22064059 TI - The use of proteomics in meat science. AB - Characterising the function of genes is a major challenge in the post-genomic era. Post-genomic tools and technologies have dramatically changed the experimental approaches by which complex biological systems can be characterised. Proteomics is an important cornerstone in functional genome characterisation, and like all other functional genomics tools, including transcriptomics and metabolomics, the aim of proteome studies is to translate genome information into useful biological insight, that will allow scientists to build and test better hypotheses, with the ultimate goal to find better solutions to challenges in food production, medicine and environmental management. In agricultural sciences as well as in all other life sciences, the implementation of proteomics and the other post-genomic tools is an important step towards achieving better product quality and a more sustainable animal production. The aim of this review is to introduce the developing field of proteomics, and to discuss the use of proteomics in meat science projects. The most frequently used technologies for characterising cellular protein expression patterns will be introduced, and some early examples of applying proteomics to meat quality research will be discussed. PMID- 22064060 TI - The vital role of science in global policy decision-making: An analysis of past, current, and forecasted trends and issues in global red meat trade and policy. AB - As global populations and economies change, the dynamics of global trade and policy change as well. In analyzing the past trends and projections for global populations, economic developments, animal product production and consumption, global trade policy, and current issues being faced, one can begin to make some predictions or projections as to how the global red meat and poultry infrastructure will change and, more importantly, point to areas where a proactive approach is necessary to shape these changes to meet the most globally beneficial end. Many issues face the global red meat industry, from food safety to animal disease, and are becoming more and more complicated as consumer knowledge increases and as politics intervene. Internationalized science is key and vital in the future of global trade policy as science can address the more informed consumer in a manner, which reduces anxiety over unknowns. The role of the industry is to provide the information and knowledge to the consumer necessary to convey the validity of globally accepted standards, which relate to ensuring consumer safety, animal welfare, and provide assurances that these standards are being met within the production sector. PMID- 22064061 TI - The science of recalls. AB - Morbidity due to foodborne illnesses in the US has decreased over the last ten years. During the same time period recalls affecting the meat and poultry industry have increased from 38 in 1993 to a peak of 128 in 2002. Recalls due to L. monocytogenes (LM) and E. coli O157:H7 have accounted for the majority of recalls in recent years, while incidence rates for these pathogens have decreased. Incidence of Salmonella and E. coli O157:H7 cases since 1996 have decreased 17% and 42% respectively while product positives in ready to eat foods for LM has decreased from 3% in 1995 to 0.75% in 2003. In response to the increasing number of recalls, members of the meat and poultry industry have developed recall plans to effectively manage a recall crisis. A detailed recall plan which is tested through mock scenarios is essential to reducing the economic and negative consumer confidence impact of recalls. PMID- 22064062 TI - Traceability from a European perspective. AB - At pan-European level there is a need for traceability systems giving information on origin, processing, retailing and final destination of foodstuffs. Such systems shall enhance consumer confidence in food; enable the regulatory authorities to identify and to withdraw health hazardous and non-consumable foodstuffs from the market. Animal feeds are an element in this "food-to-farm" approach to public health. Such feedstuffs are preliminary elements of some foods for human consumption, and hence are an inherent element of the food chain. A harmonised pan-European food traceability protocol would greatly assist authorities in detecting fraud as well as dangerous substances. The food chain comprises a range of sequential and parallel stages bridging the full spectrum from agricultural production to the consumable foodstuffs by consumers. EU legislation on traceability and the technologies needed to implement this system for meat and meat products are the focus of this paper. PMID- 22064063 TI - Traceability from a US perspective. AB - Traceability of a food consists of development of "an information trail that follows the food product's physical trail". Internationally, the US is lagging behind many countries in developing traceability systems for food in general and especially for livestock, poultry and their products. The US food industry is developing, implementing and maintaining traceability systems designed to improve food supply management, facilitate traceback for food safety and quality, and differentiate and market foods with subtle or undetectable quality attributes. Traceability, for livestock, poultry and meat, in its broadest context, can, could, or will eventually be used: (1) to ascertain origin and ownership, and to deter theft and misrepresentation, of animals and meat; (2) for surveillance, control and eradication of foreign animal diseases; (3) for biosecurity protection of the national livestock population; (4) for compliance with requirements of international customers; (5) for compliance with country-of origin labeling requirements; (6) for improvement of supply-side management, distribution/delivery systems and inventory controls; (7) to facilitate value based marketing; (8) to facilitate value-added marketing; (9) to isolate the source and extent of quality-control and food-safety problems; and (10) to minimize product recalls and make crisis management protocols more effective. Domestically and internationally, it has now become essential that producers, packers, processors, wholesalers, exporters and retailers assure that livestock, poultry and meat are identified, that record-keeping assures traceability through all or parts of the complete life-cycle, and that, in some cases, the source, the production-practices and/or the process of generating final products, can be verified. At issue, as the US develops traceback capabilities, will be the breadth, depth and precision of its specific traceability systems. PMID- 22064064 TI - Mechanisms of water-holding capacity of meat: The role of postmortem biochemical and structural changes. AB - Unacceptable water-holding capacity costs the meat industry millions of dollars annually. However, limited progress has been made toward understanding the mechanisms that underlie the development of drip or purge. It is clear that early postmortem events including rate and extent of pH decline, proteolysis and even protein oxidation are key in influencing the ability of meat to retain moisture. Much of the water in the muscle is entrapped in structures of the cell, including the intra- and extramyofibrillar spaces; therefore, key changes in the intracellular architecture of the cell influence the ability of muscle cells to retain water. As rigor progresses, the space for water to be held in the myofibrils is reduced and fluid can be forced into the extramyofibrillar spaces where it is more easily lost as drip. Lateral shrinkage of the myofibrils occurring during rigor can be transmitted to the entire cell if proteins that link myofibrils together and myofibrils to the cell membrane (such as desmin) are not degraded. Limited degradation of cytoskeletal proteins may result in increased shrinking of the overall muscle cell, which is ultimately translated into drip loss. Recent evidence suggests that degradation of key cytoskeletal proteins by calpain proteinases has a role to play in determining water-holding capacity. This review will focus on key events in muscle that influence structural changes that are associated with water-holding capacity. PMID- 22064065 TI - Effects of nitric oxide and oxidation in vivo and postmortem on meat tenderness. AB - Metabolic processes in muscle tissue in vivo result in the production of reactive oxygen species and oxidative compounds including superoxide anions and nitric oxide (NO). Reactive oxygen species can react with both lipids and proteins and often have deleterious effects, contributing to the onset of ageing and senescence as well as cell death. Nitric oxide (NO) is a free radical that is constantly produced or released throughout the body by diverse tissues and is known to influence proteolytic activity in human and rodent skeletal muscle as well as being involved in regulation of calcium homeostasis in the muscle cell. The influence of nitric oxide on development of meat tenderness has been studied through postmortem manipulation and also through in vivo studies. The effect of NO on meat tenderness is postulated to be via its regulatory effects on the proteins calpain, cathepsins, ryanodine receptor channel in the sarcoplasmic reticulum (SR) and the sarcoplasmic-endoplasmic release calcium ATPase in the SR. NO is an oxidant although the effects of NO on effector proteins can be distinguished from a direct oxidation reaction. The onset of oxidation in meat postmortem is well known to produce off-odours, discolouration and unacceptable flavours associated with rancidity. Oxidation during the immediate postmortem period appears to inhibit tenderisation during ageing, probably through an inhibitory effect of oxidation on the calpain enzyme. Oxidation of muscle tissue occurring as a result of availability of oxygen during modified atmosphere packaging may also have deleterious consequences for tenderness development during storage of meat prior to retail display. In conclusion, it is proposed that postmortem meat tenderisation is influenced by skeletal muscle's release of NO pre-slaughter and the oxidation of proteases postmortem. This proposal is compatible with the existing tenderness model and will hopefully assist in increasing the accuracy of prediction of meat tenderness. Future directions for research are discussed. PMID- 22064067 TI - The Pseudomonas aeruginosa toxin L-2-amino-4-methoxy-trans-3-butenoic acid inhibits growth and induces encystment in Acanthamoeba castellanii. AB - L-2-Amino-4-methoxy-trans-3-butenoic acid (AMB) is a toxic antimetabolite produced by the opportunistic pathogen Pseudomonas aeruginosa. To evaluate its importance as a potential virulence factor, we tested the host response towards AMB using an Acanthamoeba castellanii cell model. We found that AMB (at concentrations >= 0.5 mM) caused amoebal encystment in salt buffer, while inhibiting amoebal growth in rich medium in a dose-dependent manner. However, no difference in amoebal plaque formation was observed on bacterial lawns of wild type and AMB-negative P. aeruginosa strains. We thereby conclude that AMB may eventually act as a virulence factor, but only at relatively high concentrations. PMID- 22064066 TI - The role of interleukin-15 in inflammation and immune responses to infection: implications for its therapeutic use. AB - Interleukin-15 (IL-15) is a pleiotropic cytokine with a broad range of biological functions in many diverse cell types. It plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems. This review provides an overview of the mechanisms by which IL-15 modulates the host response to infectious agents and its utility as a cytokine adjuvant in vaccines against infectious pathogens. PMID- 22064068 TI - Laboratory investigation of dysfunctional HDL. AB - High-density lipoprotein (HDL) particles are anti-atherosclerotic, by virtue of their functions in reverse cholesterol transportation, anti-inflammation and anti oxidation. However, recent studies have cast doubt on the cardio-protective role of HDL. Structural modification and composition alteration of HDL due to chronic inflammation and acute phase responses may result in loss of normal biological function and even convert HDL into a pro-inflammatory and pro-oxidative agent. Therefore, the assessment of dysfunctional HDL has become a novel target to investigate the association between HDL and coronary artery disease risk. This review article summarizes the laboratory assessment of dysfunctional HDL. PMID- 22064069 TI - Blood folate is associated with asymptomatic or partially symptomatic Alzheimer's disease in the Nun study. AB - Asymptomatic and partially symptomatic Alzheimer's disease (APSYMAD) are a series of cognitive states wherein subjects have substantial Alzheimer's disease (AD) pathology (classification B or C by the Consortium to Establish a Registry for AD criteria), but have normal or only partially impaired cognitive function; all of these subjects are non-demented. These cognitive states may arise from the prevention or delay of clinical symptom expression by exposure to certain nutritional factors. This study examined blood levels of folate and antioxidants (i.e., carotenoids) in relation to APSYMAD, nested in the Nun study, a longitudinal study of aging and AD. Sixty elderly female subjects, who had AD on the basis of neuropathology exams, were included. Following adjustment for APOE4 status, education level, and age at blood draw, subjects with the highest blood folate levels had a higher likelihood of being in the APSYMAD group as compared to the demented (AD) group (odds ratio = 1.09, 95% CI = 1.00-1.18. p < 0.06). This association was not significantly influenced by additional adjustment for blood concentrations of carotenoids. Restriction of the population to subjects with near normal cognition on the cognitive state score (score = 1-3) indicated an elevated association with blood folate (odds ratio = 1.12, 95% CI = 1.01-1.25, p < 0.04). Blood carotenoids were not associated with APSYMAD. Thus, folate status may influence the expression of clinical symptoms of AD disease and aid in the delay or prevention of dementia. PMID- 22064070 TI - Detection of peri-synaptic amyloid-beta pyroglutamate aggregates in early stages of Alzheimer's disease and in AbetaPP transgenic mice using a novel monoclonal antibody. AB - The neurodegenerative pathology in patients with Alzheimer's disease (AD) has been associated with the progressive accumulation of aggregated and post translationally modified amyloid-beta (Abeta) species. Among them, recent studies indicate that the pyroglutamate modification of Abeta (pE(3)Abeta) catalyzed by glutaminyl cyclase might play an important role in the pathogenesis of AD. Although the effects of the pyroglutamate modification on Abeta aggregation and toxicity have been investigated, less is known about the distribution of pE(3)Abeta across the spectrum of AD and in the brains of amyloid-beta protein precursor (AbetaPP) transgenic (tg) animals. For this purpose, we generated a novel monoclonal antibody (denominated D129) that specifically recognizes pE(3)Abeta and characterized the patterns of distribution in the postmortem brain samples from AD patients divided by disease stage (Braak stage) and in AbetaPP tg mice. We found that in early stages of AD and young AbetaPP tg mice pE(3)Abeta was found in discrete linear and granular aggregates in the neuropil that co localized with the pre-synaptic protein synaptophysin and was in close opposition to dendrites labeled with MAP2. In later stages of AD and in older AbetaPP tg mice, pE(3)Abeta was abundant in diffuse and mature plaques. In conclusion, this study suggests that peri-synaptic accumulation of pE(3)Abeta might contribute to early cognitive dysfunction in AD. PMID- 22064071 TI - Endogenous secretory receptor for advanced glycation end-products inhibits amyloid-beta1-42 uptake into mouse brain. AB - The cell-surface receptor for advanced glycation end-products (RAGE) has been implicated in the development of diabetic vascular complications and Alzheimer's disease. RAGE has been considered to be involved in amyloid-beta1-42 (Abeta1-42) uptake into brain. In the present study, we demonstrate that endogenous secretory RAGE (esRAGE), a decoy form of RAGE generated by alternative RNA processing, is able to inhibit Abeta1-42 influx into mouse brain. Surface plasmon resonance and competitive binding assays revealed that human Abeta1-42 interacted with human esRAGE within the immunoglobulin V type region. We next examined the uptake and distribution of 125I-labeled human Abeta1-42 in various organs and body fluids of newly created mice overexpressing human esRAGE as well as RAGE-null and wild-type (WT) mice. The transition of the 125I-labeled Abeta1-42 from circulation to brain parenchyma peaked at 30 min after the injection into WT mice, but this was significantly blunted in esRAGE-overexpressing and RAGE-null mice. Significant reduction in 125I-labeled Abeta1-42-derived photo-stimulated luminescence were marked in ventricles, cerebral cortex, hippocampus, especially CA1 and CA3 regions, putamen, and thalamus. The results thus suggest the potential of esRAGE in protection against the development of Alzheimer's disease. PMID- 22064072 TI - Independence between GTPase active sites in the Escherichia coli cell division protein FtsZ. AB - We have analyzed the substrate kinetics of the GTPase activity of FtsZ and the effects of two different GTPase inhibitors, GDP and the slowly hydrolyzable GTP analogue GMPCPP. In the absence of inhibitors the GTPase activity follows simple Michaelis-Menten kinetics, and both GDP and GMPCPP inhibited the activity in a competitive manner. These results indicate that the GTPase active sites in FtsZ filaments are independent of each other, a feature relevant to elucidate the role of GTP hydrolysis in FtsZ function and cell division. PMID- 22064073 TI - Structural basis of gammaH2AX recognition by human PTIP BRCT5-BRCT6 domains in the DNA damage response pathway. AB - Human Pax2 transactivation domain-interacting protein (hPTIP), containing six BRCT domains, is an essential protein required for the IR induced DDR process with an unclear role. Here we report that the tandem BRCT5-BRCT6 domain of hPTIP recognizes the gammaH2AX tail, and this interaction depends on the phosphorylation of H2AX Ser139 and binding with the carboxyl ending peptide to the aminoacyl ending peptide. The 2.15 A crystal structure of hPTIP BRCT5/6 gammaH2AX complex and mutation analysis provide molecular evidence for direct interactions between PTIP and gammaH2AX. This interaction proffers a new clue to identify the role of PTIP in DDR pathways. PMID- 22064074 TI - Promiscuous interactions of human septins: the GTP binding domain of SEPT7 forms filaments within the crystal. AB - We describe the purification, crystallization and structure for the GTP-binding domain of human septin 7 (SEPT7G). We show that it forms filaments within the crystal lattice which employ both the G and NC interfaces, similar to those seen in the hetero-filament of SEPT2/6/7. The NC interface is considered promiscuous as it is absent from the hetero-filament. Such promiscuity could provide the potential for permuting monomers along a filament in order to generate diversity in hetero-polymers. On the other hand, our results suggest that the G and NC interfaces may be necessary but insufficient for determining correct hetero filament assembly. PMID- 22064075 TI - Developmental changes in the mammalian gonadotropin-inhibitory hormone (GnIH) ortholog RFamide-related peptide (RFRP) and its cognate receptor GPR147 in the rat hypothalamus. AB - The mammalian gonadotropin-inhibitory hormone (GnIH) ortholog RFamide-related peptide (RFRP) is considered to act on gonadotropin-releasing hormone (GnRH) neurons and on the pituitary to inhibit gonadotropin release and synthesis. To understand the functional significance of this neuropeptide, we investigated the physiological changes in RFRP at mRNA and peptide levels, as well as at the mRNA level of its cognate receptor, G protein-coupled receptor 147 (GPR147), in the rat hypothalamus during development. We also investigated the effects of gonadal steroids on mRNA expression levels of these molecules. In male rats, mRNA expressions of both RFRP and GPR147 increased from postnatal days 12 and 16, peaking at postnatal days 35 and 42, respectively. However, their expressions fell at postnatal day 49. In female rats, mRNA expression of RFRP continued to increase throughout development; mRNA expression of GPR147 in female rats increased from postnatal day 16, peaking at postnatal day 28, but decreased from postnatal day 35. The hypothalamic contents of RFRP on postnatal days 28 and 42 were significantly higher than on postnatal day 4 in male rats, and those on postnatal day 42 were significantly higher than those on postnatal days 4 and 28 in females. Neither orchidectomy nor ovariectomy influenced mRNA expression levels of RFRP or GPR147 in the prepubertal period when endogenous sex steroid levels were low in males and females. Administration of estradiol-17beta (E2) increased mRNA expression of RFRP in prepubertal females. These results suggest that the hypothalamic RFRP system changes during development. An ovarian sex steroid, E2, may stimulate mRNA expression of RFRP in the prepubertal period when the basal E2 concentration is low. PMID- 22064076 TI - Longer Tc-99m-mebrofenin labeling-to-administration time results in scintigraphic underestimation of liver function. AB - OBJECTIVE: Tc-99m-mebrofenin clearance rate is used to estimate hepatocellular function. This investigation studied effect of labeling-to-administration (LTA) time of Tc-99m-mebrofenin and its liver clearance rate. METHODS: A total of 15 patients, age 46 +/- 13 (range, 19-69) years, referred for routine gallbladder ejection fraction testing, were retrospectively studied. All had tests associated to normal liver, and no medical history of liver diseases was observed. Tc-99m mebrofenin scintigraphic liver clearance (MSLC) rate was determined by the standard technique based on liver uptake rate. The radiopharmaceutical was prepared at an off-site central radiopharmacy. Linear regression was used to assess relationship of LTA time and MSLC. RESULTS: The LTA was 7.6 +/- 2.0 (range, 4-12) hours. The labeling efficiency was 99.0% +/- 1.33%. The MSLC rate was 11.9%/min +/- 2.7%/min (range, 6.4-18.3). There was an inverse relationship of LTA and MSLC, expressed in the following equation: y = -0. 97x + 19.25 (R = 0.5076, P = 0.0028). The negative correlation with LTA remained when MSLC was corrected for body surface area (R = 0.4241, P = 0.0085). CONCLUSION: There is a significant underestimation of MSLC with increasing LTA time. If liver function assessment is the purpose of a hepatobiliary study, Tc-99m-mebrofenin should be administered as close to the time of radiopharmaceutical preparation as possible, preferably within 1 hour. PMID- 22064077 TI - Renal axis deviation in urinary tract abnormalities of children: the role of renal scintigraphy. AB - BACKGROUND: Urinary tract pathologies are common in children. Previous reports suggested a relationship between some renal pathologies and renal anatomic variations. This study evaluates the effect of different urinary tract abnormalities on scintigraphic renal long axis. METHODS: Children referred to our nuclear medicine department for Tc-99m dimercaptosuccinic acid and/or Tc-99m N,N ethylenedicysteine renal scintigraphies were entered consecutively. Presence of single, ectopic, or fused kidneys, extrarenal pathologies altering renal long axis, and history of renal surgery or advanced renal disease were used as exclusion criteria. If indicated, patients were assessed for vesicoureteral reflux (VUR). Long renal axis of each kidney was drawn with a line passing through the kidney's upper and lower poles using posterior image. The angle between this axis and patient's longitudinal body axis was defined as "renal angle." After defining age-groups, "age-corrected renal angle" was calculated. RESULTS: A total of 311 cases (622 kidney units) entered the study (183 females, 128 males). Mean age was 41.8 months. Mean "renal angle" was 11.7, 11.9, 14.1, 17.6, 28.5, 16.7, and 19.2 degrees in normal, mild, moderate, and severe VUR, high-grade ureteropelvic junction (UPJ) obstruction, nonobstructive pelvic dilatation, and ureterovesical junction obstruction, respectively (P = 0.000). Applying receiver operating characteristic analysis and using ultrasonography as the gold standard, renal angle deviation of 13.75 degrees led to the sensitivity of 74.6% and specificity of 70.7% to detect pyelocalyceal system dilatation. Using a "renal angle" cutoff value of 18.7 degrees, 85% sensitivity and 85% specificity were achieved for the diagnosis of high-grade UPJ obstruction. Using "age-corrected renal angle," a cutoff value of 3.9 degrees was consistent with 60% sensitivity and 73% specificity for the diagnosis of severe VUR. CONCLUSION: Considerable renal axis deviation is noted in patients with UPJ obstruction and severe VUR in children. Measurement of "renal angle" provides indirect but useful clues to the presence of urinary tract pathologies. Renal scintigraphy is a useful tool for drawing renal axis and measuring "renal angle," potentially making it useful for prediction of urinary tract system abnormalities. PMID- 22064078 TI - F-18 FDG in conjunction with 11C-choline PET/CT in the diagnosis of hepatocellular carcinoma. AB - PURPOSE: F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) alone has limited sensitivity for the diagnosis of hepatocellular carcinoma (HCC). We hoped to improve the diagnostic sensitivity by combining F-18 FDG and C-choline PET/CT. MATERIALS AND METHODS: A total of 76 consecutive patients with HCC were prospectively enrolled. Whole-body F-18 FDG PET/CT scan was performed for all patients. In those patients with negative F-18 FDG scans, a regional C-choline PET/CT scan was also performed. RESULTS: Positive F-18 FDG scans were noted in 61.1% (48/76) patients with HCC. Increased F-18 FDG uptake correlated with decreased tumor differentiation (P = 0.042). In 28 HCC patients with negative F-18 FDG scans, C-choline scan was positive in 71.4% patients. C-choline scan did not detect any significant difference between well- and moderately differentiated HCC (P = 0.585). Compared with F-18 FDG scan, C choline scan showed a trend toward an improved detection of well-differentiated HCC (66.7% vs. 35.7%, NS). For detection of moderately differentiated HCC, the sensitivity of C-choline and F-18 FDG PET/CT was similar (85.7% vs. 72.0%, P = 0.648). The dual-tracer modality improved the diagnostic sensitivity of F-18 FDG PET/CT alone from 63.1% to 89.5% (P < 0.001). CONCLUSIONS: F-18 FDG in conjunction with C-choline increases the sensitivity of PET/CT in detecting HCC. PMID- 22064079 TI - Early dynamic versus late static lymphoscintigraphy for the identification of sentinel lymph nodes in breast cancer. AB - PURPOSE: Sentinel lymph node (SLN) biopsy is an established method for the identification of early breast cancer metastases. SLN lymphoscintigraphy is pivotal in many cases, but the diagnostic value of early dynamic versus late static imaging procedures remains unclear. The objective of this study was to evaluate the diagnostic value of early dynamic versus late static imaging in the identification of SLN in breast cancer patients. MATERIALS AND METHODS: A total of 104 consecutive female patients who were referred for SLN scintigraphy prior to breast cancer surgery were included in this retrospective study. All patients underwent both a 20-minute dynamic lymphoscintigraphy and a 2-hour static acquisition. The images were independently evaluated for the presence, location, and numbers of SLN and echelon nodes in a blinded and random manner by 2 trained observers. Any discrepancy was solved by a third party arbitrator. RESULTS: SLN was identified in 101 of 104 (97%) patients on the static images versus 41 of 104 (39%) of the patients based on the dynamic acquisition. The combined use of dynamic and static images did not increase the diagnostic performance versus late lymphoscintigraphy alone. CONCLUSIONS: Identification of SLN by lymphoscintigraphy in breast cancer can be performed using a 2-hour static image alone. PMID- 22064080 TI - Predictive value of preablation stimulated thyroglobulin and thyroglobulin/thyroid-stimulating hormone ratio in differentiated thyroid cancer. AB - PURPOSE: Recent studies have shown that thyroglobulin (Tg) concentration is a useful tumor marker in follow-up of differentiated thyroid cancer (DTC) patients after thyroidectomy and subsequent radioiodine (I-131) therapy. However, its role is controversial after total or near-total thyroidectomy before the first I-131 ablative treatment. So, we used thyroid-stimulating hormone (TSH) levels to normalize predictive values of Tg for DTC. METHODS: The study was a retrospective analysis. A total of 244 patients with DTC who had undergone a total thyroidectomy and subsequent I-131 therapy were included. Exclusion criteria were patients with high serum Tg antibody (TgAb) concentration and in whom it was not measured. Patients were divided into 2 groups as M1 and M0, according to whether the patient present with or without distant metastases. RESULTS: Preablative stimulated Tg in group M0 ranged between 0.1 and 348.9 ng/mL and group M1 between 0.2 and 1000 ng/mL. Tg/TSH ratios ranged 0.000667 to 12.143 ng/IU and 0.002948 to 12500 ng/IU. Both Tg and Tg/TSH values were significantly different between the 2 groups (the Wilcoxon rank sum test: Tg P < 0.0001 [z = 8.785]; Tg/TSH P < 0.0001 [z = 8.850]). The areas under receiver operating characteristic curves for Tg concentrations and Tg/TSH ratios were 0.913 and 0.916, respectively. CONCLUSION: Both Tg and Tg/TSH ratios might be considered predictive markers for metastases of DTC just after total thyroidectomy before the first I-131 ablative therapy. PMID- 22064081 TI - Planning and conducting meetings effectively, part I: planning a meeting. AB - Meetings are held by leaders for many purposes, including conveying information, raising morale, asking for opinions, brain storming, making people part of the problem-solving process, building trust, getting to a consensus, and making decisions. However, many meetings waste time, some undermine the leader's power, and some decrease morale. Part I of this series of articles gives some tips on basic planning for decision-making meetings. Part II of this series of articles analyzes selected components of decision-making meetings. Part III of this series will be on how the chairperson keeps decision-making meetings on track to make them efficient and productive. PMID- 22064082 TI - When should F-18 FDG PET/CT be used instead of 68Ga-DOTA-peptides to investigate metastatic neuroendocrine tumors? PMID- 22064083 TI - Asymptomatic rib cavernous hemangioma. PMID- 22064084 TI - Atypical sites of bony metastases in a prostate cancer patient. PMID- 22064085 TI - Unsuspected perforated Richter hernia in the inguinal canal detected by F-18 FDG PET/CT. PMID- 22064086 TI - Negative amyloid PET imaging in a patient with probable Alzheimer's disease. PMID- 22064087 TI - Polycystic kidney disease: renal cyst infection detected on F-18 FDG PET/CT. PMID- 22064088 TI - Rare cerebral and pulmonary metastases from low-grade basal cell adenocarcinoma of the parotid gland. PMID- 22064089 TI - Ventriculoperitoneal shunt leakage into a breast implant demonstrated by radionuclide cisternography. PMID- 22064090 TI - Munchhausen syndrome presenting as fever of unknown origin: diagnosis by F-18 FDG PET/CT. PMID- 22064091 TI - Effect of mobile cell phone ringing on function of gamma camera. PMID- 22064092 TI - Ovarian thecoma mimicking carcinoma on F-18 FDG PET in a postmenopausal woman with elevated CA-125. PMID- 22064093 TI - Predominant IgG4 disease and concurrent early-stage rectal cancer. PMID- 22064094 TI - A hepatoid adenocarcinoma of the stomach with liver metastasis mimicking hepatocellular carcinoma detected by F-18 FDG PET/CT imaging. PMID- 22064095 TI - Unilateral diffusely increased muscle uptake of F-18 FDG in a patient with hemiparesis due to stroke. PMID- 22064096 TI - Scintigraphic demonstration of ectopic thyroid tissue in a thyroglossal duct cyst in the presence of a normal thyroid. PMID- 22064097 TI - Detection of a sinus of Valsalva aneurysm by F-18 FDG PET/CT imaging. PMID- 22064098 TI - F-18 FDG uptake in focal fatty infiltration of liver mimicking hepatic malignancy on PET/CT images. PMID- 22064099 TI - Differentiated thyroid cancer with epiphora: detection of nasolacrimal duct obstruction on I-131 SPECT/CT. PMID- 22064100 TI - Tc-99m-MIBI-negative parathyroid adenoma in primary hyperparathyroidism detected by C-11-methionine PET/CT after previous thyroid surgery. PMID- 22064101 TI - Diagnosis of cardiac sarcoidosis through mismatched defects seen on N-13 NH3/F-18 FDG cardiac PET. PMID- 22064102 TI - Current readings in nuclear medicine. PMID- 22064103 TI - PET/CT imaging of thyroid cancer. AB - Positron emission tomography (PET) is a highly sensitive, low invasive technology for cancer biology imaging. The role of F-18 FDG PET/CT in differentiated thyroid cancer (DTC) is well established, particularly in patients presenting with elevated Tg levels and negative radioactive iodine WBS. It has been demonstrated that F-18 FDG uptake represents less differentiated thyroid cancer cells or dedifferentiated cells and PET positive lesions are more likely to be resistant to I treatment. The uptake of F-18 FDG is related to tumor size, thyroid capsule invasion and histological variants with a poor prognosis. As in other cancers, early detection of recurrences improves outcomes and survival. I PET/CT can also be used to image the patients with DTC, similarly to I WBS. Compared with F-18 FDG PET/CT, its spatial resolution is only slightly degraded but increasing the imaging time reduces this difference. In addition, F-18 FDG PET/CT has been found helpful in the management of patients with anaplastic and medullary thyroid cancer. Other radiopharmaceuticals such as Ga-DOTATOC and F-18 DOPA may provide complimentary information to F-18 FDG PET/CT in the detection of recurrent thyroid cancer. PMID- 22064104 TI - Yttrium-90 time-of-flight PET/CT is superior to Bremsstrahlung SPECT/CT for postradioembolization imaging of microsphere biodistribution. PMID- 22064105 TI - Impact of F-18 FDG PET-CT for the diagnosis and management of infection in JARVIK 2000 device. PMID- 22064106 TI - Early gastric cancer detected by 2-hour delayed FDG PET with the water gastric distention method. PMID- 22064107 TI - Lack of concordance between the F-18 fluoromisonidazole PET and the F-18 FDG PET in human glioblastoma. PMID- 22064108 TI - Simultaneous detection of breast tumor resection margins and radioguided sentinel node biopsy using an intraoperative electronically collimated probe with variable energy window: a case report. PMID- 22064109 TI - Three-phase skeletal scintigraphy in pachydermoperiostosis. PMID- 22064110 TI - Preoperative evaluation of possible cross-circulation in conjoined twins by hepatobiliary scintigraphy. PMID- 22064111 TI - FDG PET/CT detects malignant lymphoma invading the penis. PMID- 22064112 TI - Unusual Tc-99m methylene diphosphonate uptake by clinically suspected adrenal metastases from hepatocellular carcinoma. PMID- 22064113 TI - Primary pulmonary osteosarcoma: PET/CT and SPECT/CT findings. PMID- 22064114 TI - Round cell liposarcoma presenting as an FDG-positive primary with an FDG-negative retroperitoneal metastasis: a pitfall for F-18 FDG PET/CT imaging. PMID- 22064115 TI - Lower neck neurilemmoma can masquerade as lymph node metastasis on FDG PET/CT in patient with nasopharyngeal carcinoma. PMID- 22064116 TI - Atypical presentation of plasma cell leukemia secondary to multiple myeloma detected by F-18 FDG PET/CT. PMID- 22064117 TI - Multistage high-dose I-131 treatment for a nonthyroidectomized patient with metastatic differentiated thyroid cancer. PMID- 22064118 TI - Ectopic kidney mimicking a Meckel's diverticulum on Tc-99m pertechnetate scan. PMID- 22064119 TI - F-18 FDG PET/CT imaging of endogenous Cushing syndrome. PMID- 22064120 TI - Image gently: go with the guidelines. PMID- 22064121 TI - Binding of the plant hormone kinetin in the active site of Mistletoe Lectin I from Viscum album. AB - The crystal structure of the ribosome inhibiting protein Mistletoe Lectin I (ML I) derived from the European mistletoe, Viscum album, in complex with kinetin has been refined at 2.7A resolution. Suitably large crystals of ML-I were obtained applying the counter diffusion method using the Gel Tube R Crystallization Kit (GT-R) on board the Russian Service Module on the international space station ISS within the GCF mission No. 6, arranged by the Japanese aerospace exploration agency (JAXA). Hexagonal bi-pyramidal crystals were grown during three months under microgravity. Before data collection the crystals were soaked in a saturated solution of kinetin and diffraction data to 2.7A were collected using synchrotron radiation and cryogenic techniques. The atomic model was refined and revealed a single kinetin molecule in the ribosome inactivation site of ML-I. The complex demonstrates the feasibility of mistletoe to bind plant hormones out of the host regulation system as part of a self protection mechanism. PMID- 22064122 TI - Modulation of fibrillation of hIAPP core fragments by chemical modification of the peptide backbone. AB - The well-ordered cross beta-strand structure found in amyloid aggregates is stabilized by many different side chain interactions, including hydrophobic interactions, electrostatic charge and the intrinsic propensity to form beta sheet structures. In addition to the side chains, backbone interactions are important because of the regular hydrogen-bonding pattern. beta-Sheet breaking peptide analogs, such as those formed by N-methylation, interfere with the repetitive hydrogen bonding pattern of peptide strands. Here we test backbone contributions to fibril stability using analogs of the 6-10 residue fibril core of human islet amyloid polypeptide, a 37 amino acid peptide involved in the pathogenesis of type II diabetes. The Phe-Gly peptide bond has been replaced by a hydroxyethylene or a ketomethylene group and the nitrogen-atom has been methylated. In addition, we have prepared peptoids where the side chain is transferred to the nitrogen atom. The backbone turns out to be extremely sensitive to substitution, since only the minimally perturbed ketomethylene analog (where only one of the -NH- groups has been replaced by -CH(2)-) can elongate wildtype fibrils but cannot fibrillate on its own. The resulting fibrils displayed differences in both secondary structure and overall morphology. No analog could inhibit the fibrillation of the parent peptide, suggesting an inability to bind to existing fibril surfaces. In contrast, side chain mutations that left the backbone intact but increased backbone flexibility or removed stabilizing side-chain interactions had very small effect on fibrillation kinetics. We conclude that fibrillation is very sensitive to even small modifications of the peptide backbone. PMID- 22064123 TI - A retrospective analysis of lesser metatarsophalangeal joint fusion as a treatment option for hammertoe pathology associated with metatarsophalangeal joint instability. AB - Complex hammer digit deformity is commonly associated with instability of the metatarsophalangeal joint. Restoring joint stability is critical for digit alignment and function and can be challenging and unpredictable. Lesser metatarsophalangeal joint fusion might be an alternative treatment to the current soft tissue balancing, repair, and extra-articular osseous procedures used to treat joint instability. The present study was a retrospective chart and radiographic review of the pooled outcomes of 31 consecutive lesser metatarsophalangeal joint fusion procedures performed by 3 independent surgeons from May 2004 to September 2009. The clinical and radiographic outcomes were analyzed with descriptive and inferential statistics. The overall interval to radiographic union was 8.69 +/- 1.7 weeks (range 6 to 12 and 95% confidence interval 7.9 to 9.4). The overall period to clinical union was 10.25 +/- 4.5 weeks (range 4 to 22 and 95% confidence interval 8.5 to 11.9). The mean duration of non-weight-bearing was 4.71 +/- 1.74 weeks, followed by 5.09 +/- 2.8 weeks of guarded weight-bearing with a brace. Complications included nonunion in 4 (12.90%), hardware breakage in 2 (6.45%), and soft tissue infection in 1 (3.23%). Patients demonstrated a statistically significant reduction in pain (p = .035) and improved digit alignment after the procedure that enabled full return to unrestricted weight-bearing activities without limitations or the need for orthoses. These findings support metatarsophalangeal joint fusion as an alternative treatment of lesser digit metatarsophalangeal joint instability associated with hammer digit deformities that obviate the need for concomitant soft tissue procedures such as plantar plate repair or tendon balancing procedures. PMID- 22064124 TI - Surgical technique for combined Dwyer calcaneal osteotomy and peroneal tendon repair for correction of peroneal tendon pathology associated with cavus foot deformity. AB - Peroneal tendon pathology is commonly seen in patients with underlying pes cavus. The Dwyer calcaneal osteotomy is a useful adjunctive procedure to address the heel varus component of the cavus foot deformity, especially in the presence of concomitant peroneal tendon pathology. The lateralizing heel osteotomy using a wedge resection can effectively reduce future stress on the repaired peroneal tendons, although technical challenges arise when attempting to perform both tendon repair and heel osteotomy through the same incision. Specific principles must be followed to achieve adequate exposure of the desired structures, obtain desired correction of the deformity, and avoid complications such as sural neuritis. In the present report, the surgical principles and technical pearls are highlighted in a pictorial demonstration of preoperative planning for calcaneal wedge resection, incision placement, osteotomy guide pin technique, fixation pearls, and peroneal tendon repair and transfer. PMID- 22064125 TI - Chondroblastoma of the talus: a case report and literature review. AB - Chondroblastoma is a rare, benign cartilaginous neoplasm that accounts for approximately 1% of all bone tumors, and approximately 4% of all chondroblastomas arise in the talus. Here we report a case of chondroblastoma in the left talus. The 22-year-old male patient presented with a 16-month history of ankle pain. Based on radiological and pathological examination, we diagnosed the patient with chondroblastoma. A posterolateral approach was used to allow access to the lesion. After curettage, the allogenic bone chips were packed into the talar body defect. After 2 years' follow-up, we found no recurrence or metastasis of chondroblastoma, suggesting our surgery procedure was effective. PMID- 22064126 TI - Fungal osteomyelitis of calcaneus due to Candida albicans: a case report. AB - Osteomyelitis can be a challenging entity to treat. Because of the emergence of risk factors, including broad-spectrum antibiotics, intravenous drug abuse, immunocompromised hosts, and other factors, opportunistic pathogens have increased in prevalence in bone infections. A review of the published data revealed few reported cases of fungal osteomyelitis localized to the foot. In the present report, we describe a rare case of fungal osteomyelitis localized to the calcaneus in an elderly female patient who was successfully treated with surgical debridement and a 6-week course of oral fluconazole. PMID- 22064127 TI - Consumer perception of meat quality and implications for product development in the meat sector-a review. AB - In the first part of the paper, the Total Food Quality Model is used as a frame of reference for analysing the way in which consumers perceive meat quality, drawing mainly on European studies involving beef and pork. The way in which consumers form expectations about quality at the point of purchase, based on their own experience and informational cues available in the shopping environment, is described, as well as the way in which quality is experienced in the home during and after meal preparation. The relationship between quality expectations and quality experience and its implications for consumer satisfaction and repeat purchase intent is addressed. In the second part of the paper, and building on the insights obtained on subjective quality perception, possibilities for consumer-oriented product development in the meat sector are addressed. Issues dealt with here are branding, differentiation by taste, healthiness and convenience, and by process characteristics like organic production and animal welfare. PMID- 22064128 TI - Prediction of color and pH measurement throughout boneless center-cut pork loins. AB - Boneless pork loins (N=95) divided into three groupings based on National Pork Producers Council color standards were utilized to characterize changes in color and pH throughout the loin. CIE L(*), CIE a(*), CIE b(*), saturation, and hue angle differed (P<0.05) for color category and chop position. A color category by position interaction (P<0.05) existed only for pH values. These differences in color and pH measures throughout the loin indicate that one measurement may not characterize the entire boneless loin. For all color and pH measures significant orthogonal and polynomial contrasts existed, therefore, separate regression equations were developed for each color category to predict position response. Multiple regression equations were significant for most objective measures of color and pH, but the low R(2) values indicate that these models provide little information as to changes in color and pH throughout the boneless pork loin. PMID- 22064129 TI - Physicochemical, microbiological and sensory attributes for the characterization of Greek traditional sausages. AB - Physicochemical, microbiological and sensory analyses were performed on 67 samples of Greek traditional sausages. The following physicochemical attributes were recorded: moisture 49.17%+/-7.05, protein 17.62%+/-2.67, fat 29.74%+/-8.02 and ash content 2.99%+/-0.55, moisture/protein ratio 2.83+/-0.5. pH value 5.48+/ 0.49, water activity (a(w)) 0.959+/-0.015, total grill losses 12.81%+/-5.27 and fat grill losses 9.64%+/-4.36. The microbial counts, expressed as log(10)cfu/g, were for aerobic plate count 8.22+/-0.5, lactic acid bacteria 7.45+/-0.66, Brochothrix thermosphacta 7.02+/-1.21, pseudomonads 6.88+/-1.33 and yeasts 5.39+/ 1.03. Mean sensory scores, on a five-point hedonic scale, were 4.46+/-0.63 for appearance, 4.14+/-0.63 for firmness, 3.80+/-0.97 for flavour and 4.12+/-0.52 for overall quality. The discriminant analysis have shown that, based on their pH and a(w) values, 74.6% of sausages were classified as easily perishable, 19.4% as perishable and 5.9% as shelf-stable. Also, 4.4% of sausages had fat content less than 15%, 23.8% from 15 to 25%, 46.2% from 25 to 35% and 25.3% more than 35%. Principal component analysis has shown that the first two components (PC1 PC2) account for 44.1% of the total variance. PC1 was related to water activity, ash, moisture and fat content, flavour, Br. thermosphacta and pseudomonads count, and to a lesser extent to cross section quality. PC2 was related to aerobic plate count, lactic acid bacteria and moisture content. PMID- 22064130 TI - Green hams electrical impedance spectroscopy (EIS) measures and pastiness prediction of dry cured hams. AB - The objective of this study was to assess the value of electrical impedance spectroscopy (EIS) as a predictor of certain dry-cured ham sensory properties in green hams of different technological meat qualities and processed commercially. Measurements of technological meat quality (weight, ham conformation, subcutaneous fat thickness, pH(45) and pH(u)) and some sensory properties (adhesiveness, hardness, crumbliness, pastiness, fibrousness and saltiness) were carried out on the Biceps femoris (BF) and Semimembranosus (SM) muscles. The electrical parameters, R(o), R(inf), ratio (R(inf)/R(o)), F(c) and alpha, were obtained with EIS equipment applied to two different regions of the ham at 36 h post mortem (BF and SM). Principal component (PC) analysis was used to describe the relationship between sensory properties and electrical parameters. For BF muscle there were no clear relationships between the electrical parameters and the sensory properties. However, for SM muscle, pastiness was correlated positively with the ratio and F(c) obtained by EIS. None of the electrical parameters obtained by EIS were able to differentiate between groups of hams classified according to their level of pastiness in the BF muscle. However, in the SM muscle, the origin of the pastiness was related to the use of PSE meat and was predicted by the electrical impedance measurements. The EIS prototype correctly detected 69.2 and 56.0% (for SM and BF muscles, respectively) of the problem hams in terms of pastiness. These results could be of use in the selection of the raw material to reduce the incidence of dry-cured hams with defective texture. PMID- 22064131 TI - Linear hydrocarbons content of intramuscular lipids of dry-cured Iberian ham. AB - This study has been carried out to determine the linear hydrocarbons content (n alkane and n-alkene) in intramuscular lipids (biceps femoris muscle) of dry-cured Iberian ham considering "feeding system" (Montanera: fed on acorns and pasture and concentrate feed) and "genotype" (hams from Iberian pure pigs and hams from Iberian crossbreed with Duroc in a 50%). The linear hydrocarbons from n-C(14) to n-C(32) range were present in the four studied groups. n-Alkenes fraction (60-76 mg/kg of intramuscular fat) was higher than n-alkanes fraction (34-38 mg/kg). The most abundant n-alkane and n-alkene were the shortest chain ones. Feeding and genotype did not influence linear hydrocarbons content (neither n-alkanes nor n alkenes). PMID- 22064132 TI - Water characteristics in cooked beef as influenced by ageing and high-pressure treatment-an NMR micro imaging study. AB - The water characteristics in cooked pressure-heat treated (45 degrees C for 45 min prior to pressurisation at 150 MPa for 30 min) and non-pressurised, cooked (control) samples of beef Longissimus aged for 1, 3, 8 or 16 days were studied by nuclear magnetic resonance microscopy. A multi-echo sequence was used to obtain T2 images, and independent of ageing period, the T2 values were found to be lower in pressure-heat treated meat revealing alterations in water characteristics of pressure-treated, cooked meat compared with cooked meat. With increasing ageing duration, the T2 values in both pressure-treated, cooked and cooked meat decreased indicating that the water became more tightly trapped in the protein network. In addition, independent of length of ageing period the relationship between cooking loss in the cooked meat and transverse relaxation differed between non-pressurised and pressure-treated meat, which reveals that the mechanisms changing the water properties in beef during ageing are different from those occuring during pressure-heat treatment of meat. PMID- 22064133 TI - Effect of linseed feeding at similar linoleic acid levels on the fatty acid composition of double-muscled Belgian Blue young bulls. AB - The effect of including linseed [extruded (EL) or crushed (CL)] instead of whole soybeans (S) in the finishing diet of double-muscled Belgian Blue young bulls on the fatty acid composition of the longissimus thoracis, triceps brachii and subcutaneous fat was investigated. The dietary supply of C18:2n-6 was similar in the three diets, while in the EL and CL diet the supply of C18:3n-3 was equal. No effects of diet on the saturated, monounsaturated and branched chain fatty acids were found. Including linseed in place of whole soybeans increased the total intramuscular n-3 fatty acid content significantly, mainly as C18:3n-3, while no significant effect on the total and individual n-6 fatty acid incorporation was observed in the intramuscular fat. As a consequence of the higher n-3 content, the n-6/n-3 ratio was decreased by linseed feeding. In contrast with the intramuscular fat, the subcutaneous fat showed a significantly increased C18:3n-3 proportion accompanied by a significantly decreased C18:2n-6 proportion when linseed was fed. Diet did not influence the c9t11CLA content in the intramuscular or the subcutaneous fat. PMID- 22064134 TI - Does the newly discovered calpain 10 play a role in meat tenderization during post-mortem storage? AB - The objective was to study calpain 10 during meat tenderization. Western assays were developed and changes in calpain 10, tenderization level and desmin were determined in Longissimui (LTL) during post-mortem storage. A comparison between some characteristics of calpains 1, 2 and 10 indicated differences in the pI and sub-cellular distribution. Tenderness improved gradually during post-mortem storage and was accompanied by a decline in intact desmin level. Western analysis indicated that calpain 10 is present in sheep LTL probably as two proteins (MW 73.6 and 70.7 kDa). Post-mortem storage caused a decline in the level of the 73.6 and 70.7 kDa proteins in the sarcoplasmic fraction and a concomitant increase in these proteins in the myofibrillar fraction. Changes in the myofibrillar calpain 10 proteins were strongly correlated with the rate of tenderization. To conclude, calpain 10 proteins are present in sheep LTL and the sub-cellular distribution is dynamic during post-mortem storage. PMID- 22064135 TI - A procedure to determine the water-binding capacity of meat trimmings for cooked sausage formulation. AB - An attempt was made to determine the water-binding capacity of each individual trimming in a multicomponent system. Three types of experimental cooked sausages (finely chopped luncheon sausage, coarsely chopped sausage and ring sausage with potato starch) were made of five different meat trimmings: two pork trimmings and two beef trimmings, and one beef trimming used as a replacer. The water-binding was determined by the Tuominen-Honkavaara method by stepwise addition of water (basic formulation and four water additions) to the formulations and determining the firmness by a consistometer. The water-binding of each trimming was obtained by replacing the trimming by an additonal trimming. A total of 3 sausage types*5 meat trimmings*5 water levels giving 75 experimental batches of 5 kg each were made. The average water-binding values of the same meat trimming combination in each sausage type were practically the same, and therefore the total averages for the same meat trimming combinations of each of the three sausage types were used for the subsequent calculations. The determination of the water-binding values of the meat trimmings were solved by forming five equations with four unknowns each, and then solving the unknowns using Microsoft Excel's 'Solver' function. By this procedure it was possible to determine the water-binding of individual meat trimmings in sausage systems. This procedure can be used for the determination of the technological properties of meats for linear programming. PMID- 22064136 TI - Microbiological conditions of detained beef carcasses before and after removal of visible contamination. AB - The microbiological conditions of carcasses detained for the removal of visible contamination at four beef packing plants were examined. The numbers of aerobes and Escherichia coli recovered from most visibly contaminated sites did not exceed numbers generally regarded as acceptable for beef carcasses. The numbers of bacteria at visibly contaminated sites were reduced when those sites were trimmed, but additional and/or routine decontaminating treatments after trimming gave greater reductions in numbers at three of the plants. At each plant, at the end of the dressing process, the microbiological condition of the carcasses that had been detained was similar or superior to the condition previously determined for carcasses routinely produced from the process. PMID- 22064137 TI - Prerigor infusion of lamb with sodium chloride, phosphate, and dextrose solutions to improve tenderness. AB - Combinations of sodium chloride, phosphate, and dextrose solutions were infused prerigor into lamb carcasses to evaluate effects on tenderness, palatability, color change and microbiological growth during simulated retail display. Each carcass (n=48) was randomly assigned to one of the following: (1) deionized water (dH(2)O), (2) 2% NaCl (S), (3) 3% dextrose (D), (4) 0.5% tri-polyphosphate (P), (5) 2% NaCl and 3% dextrose (SD), (6) 2% NaCl and 0.5% tri-polyphosphate (SP), (7) 0.5% tri-polyphosphate and 3% dextrose (PD), and (8) 2% NaCl, 0.5% tri polyphosphate, and 3% dextrose (SPD). The right side was pumped to 120% its original green weight and the corresponding left side served as the paired control in a nested design. The SD, SP and SPD solutions improved (P<0.05) Warner Bratzler shear force values (WBS), sensory panel evaluations for tenderness, decreased cook loss, and increased ultimate pH when compared with their corresponding controls. In addition, no adverse affects on color or microbiological growth were observed for any of the treatments. PMID- 22064138 TI - Quantifying the extent of variation in the eating quality traits of the M. longissimus dorsi and M. semimembranosus of conventionally processed Irish beef. AB - The aim of this investigation was to quantify the scale of variation in the eating quality of two commercial beef muscles, M. longissimus dorsi (LD) and M. semimembranosus (Sm). Both the LD and Sm were excised from steers (n=81) and heifers (n=81) (classification grade O4H, O4L, R4H, R4L) within 48 h postmortem, vacuum packaged and stored at 4 degrees C until tested for eating quality at 14 days postmortem. Quality measurements analysed were: pH, Warner Bratzler shear force, sensory attributes, sarcomere length, Hunter L a b muscle and subcutaneous fat colour and chemical composition. Extent of variation in many eating quality measurements, with the exception of most sensory attributes and subcutaneous fat colour, depended on gender, classification grade or a combination of both. The LD was more variable than the Sm for most quality attributes and heifers were more variable than steers. No one carcass grade was more variable over all attributes analysed; with different grades causing higher or lower variances within certain attributes. Knowledge of the current scale of variation in the eating quality of beef is required by the meat industry, and is one that requires further research. PMID- 22064139 TI - Effect of proteolytic enzyme activity and heating on the mechanical properties of bovine single muscle fibres. AB - The effect of proteolysis and heating on the mechanical properties of single muscle fibres isolated from bovine M. semitendinosus was investigated. Short incubations with MU-calpain (pH 7.5) and cathepsin B (pH 5.6) at room temperature reduced (P<0.01) the raw fibre strength by 50%. After subsequent heating, MU calpain-incubated fibres were 20% weaker and cathepsin B-incubated fibres 50% weaker than heated controls. Fibres were incubated for 8 days at 2 degrees C under post-mortem like pH conditions (pH 5.6) or pH conditions optimal for the calpains (pH 7.5). At pH 5.6 no significant weakening of the fibres was observed when incubations were performed in 0.1, 1 or 10 mM Ca(2+). In contrast, incubation in 1 or 10 mM Ca(2+) at pH 7.5 decreased the strength of the fibres. Addition of the protease inhibitors E-64 or PD150,606 prevented this weakening, suggesting that the weakening is caused by proteolyses and not directly by Ca(2+). PMID- 22064140 TI - Utilization of response surface modeling to evaluate the effects of non-meat adjuncts and combinations of PSE and RFN pork on water holding capacity and cooked color in the production of boneless cured pork. AB - Boneless cured pork was produced from combinations of pale, soft, and exudative (PSE) and red, firm, and non-exudative (RFN) semimembranosus muscle. Response Surface Methodology was utilized to determine the effects of soy protein concentrate (SPC), sodium caseinate (SC), and modified food starch (MFS) on the water holding capacity and cooked color in a chunked and formed product. Fifteen ingredient combinations were replicated three times for each PSE and RFN combination giving 75 treatments per replication. Utilization of SPC decreased (P<0.01) cooking loss and redness while increasing (P<0.01) yellowness. MFS decreased (P<0.01) expressible moisture, and both MFS and SC increased (P<0.05) cooked redness while decreasing (P<0.01) cooked lightness. Product formulations using these adjuncts demonstrate potential to improve the water-holding capacity and cooked color in PSE as well as RFN pork. This research also demonstrated that diluting RFN pork with no more than 25% PSE pork permits the formation of a high quality boneless deli ham roll. PMID- 22064141 TI - Carcass and meat quality of selected final hybrids of pigs in the Czech Republic. AB - The objective of this work was to compare the quality of carcass and meat in the selected crossbred pigs used in the Czech Republic. A total of 200 pigs that arose from four crossbreeding was studied; the dam line was in all combination of hybrids represented by Czech Large White * Landrace. Sire line included Large White * Belgian Landrace (I), Hampshire * Pietrain (II), Duroc * Pietrain (III) and Czech meat pig (IV). Influence of crossbreeding on lean meat percentage and muscle depth was statistically highly significant (P<0.001), influence on fat depth was evident (P<0.05). Differences in pH(1) value among the individual final hybrids were not statistically significant but variance of pH(24) value was highly notable (P<0.001). All colour parameters (L(*), a(*), b(*) values), drip loss and exudate also were influenced by hybrid combination (P<0.001). Influence of crossbreeding on intramuscular fat content was not statistically significant (P=0.067). Higher content of intramuscular fat was determined in the hybrids with Duroc breed in sire line. In the whole group, 8.5% pig with PSE defect was found. By comparison of all the various hybridisation, positive influence of Hampshire breed on the carcass quality and negative influence on meat quality was confirmed. On the other hand, meat quality is positively influenced Duroc and Czech meat pig breeds. PMID- 22064142 TI - The relationship between meat tenderization, myofibril fragmentation and autolysis of calpain 3 during post-mortem aging. AB - The objective was to study the potential role of calpain 3 in postmortem myofibril breakdown and meat tenderization. We determined the temporal changes in calpain 3 protein in the ovine m. longissimus thoracis et lumborum (LTL, n=4) during post-mortem storage. Concurrently, we also determined the kinetics of tenderization level, changes in MFI, degradation of nebulin and desmin, and autolysis of calpain 1. The autolysis of calpains 1 and 3 were strongly correlated with the kinetics of tenderization and changes in MFI. The best correlation was between the appearance of the autolyzed calpains 1 and 3 and nebulin degradation. Taken together, the results indicated that calpains 1 and/ or 3 might be playing a key role in post-mortem tenderization of LTL via the proteolysis of specific muscle structural proteins such as nebulin. This is the first report that relates calpain 3 to myofibrillar protein degradation in post mortem skeletal muscle. PMID- 22064143 TI - Interrelationships of breed type, USDA quality grade, cooking method, and degree of doneness on consumer evaluations of beef in Dallas and San Antonio, Texas, USA. AB - The objective of this research was to evaluate the consumer controlled factors of cooking method and degree of doneness on top loin steaks from different USDA quality grades (Low Choice, High Select or Low Select) and breed-types (English, Continental European Cross or Brahman Cross). In addition, cities within the same region were evaluated for differences in consumer controlled factors and palatability responses. The in-home product test was conducted in Dallas and San Antonio, Texas, USA. Consumers (n=173) evaluated steaks for overall like (OSAT), tenderness (TEND), juiciness (JUIC), and flavor (FLAV) using 23-point hedonic scales. Respondents in Dallas cooked their steaks to higher degrees of doneness than did those in San Antonio. Outdoor grilling was the most frequently used method of cookery for steaks in both cities. Generally, consumers in San Antonio gave higher palatability ratings to Choice steaks and Dallas consumers gave higher ratings to Select steaks. The interactions of city*cooking method, breed type*cooking method, and degree of doneness*cooking method were significant for all palatability attributes. In addition, the interaction of cooking method*quality grade was significant for TEND, JUIC, and FLAV. Warner-Bratzler shear (WBS) force was determined on a steak from each strip loin. Steaks from Continental European Cross cattle and Low Choice carcasses had the lowest WBS values. Differences in consumer preparation of beef top loin steaks present very unique challenges for the beef industry. Consumer information programs may serve a valuable role in connecting consumer perceptions with the preparation techniques needed to consistently achieve satisfaction. PMID- 22064144 TI - Effect of dietary alpha-linolenic acid and vitamin E on the fatty acid composition, storage stability and sensory traits of rabbit meat. AB - The synergistic effect of dietary linolenic acid and vitamin E on the oxidative stability and nutritional and eating characteristics of fresh and stored rabbit meat was studied. One-hundred hybrid male rabbits were divided into two homogenous groups and fed ad libitum two diets differing in the amount of sunflower and flaxseed and in the level of alpha-tocopherol, as follows: control diet: 0.08 kg kg(-1) sunflower, 50 mg kg(-1) alpha-tocopheryl-acetate and LNA-VE diet: 0.08 kg kg(-1) flaxseed, 200 mg kg(-1) alpha-tocopheryl-acetate. At 85 days, 20 rabbits per group were slaughtered and the thiobarbituric-acid reactive substances (TBA-RS), chemical composition, fatty acid profile and sensory quality were assessed on the longissimus dorsi muscles (fresh and stored for 8 days at 4 degrees C). The proximate composition of the fresh muscle was not significantly affected by the dietary treatment. Rabbits fed the LNA-VE diet showed a good capability to elongate and desaturate linolenic acid and this diet enriched the n 3 PUFA content of the meat without affecting its peroxidative stability. The sensory quality of the fresh and stored muscle was slightly affected by the dietary treatment, even though final tenderness (fresh meat) and overall acceptability (stored meat) of the LNA-VE rabbits showed significantly higher scores. PMID- 22064145 TI - Lipolysis and lipid oxidation in fermented sausages depending on different processing conditions and different antioxidants. AB - Lipolysis and lipid oxidation in Mediterranean and North Europe type sausages were studied in relation to raw material, processing conditions and additives. In particular the effect of ascorbic acid, nitrites and spices was evaluated. Lipolysis was measured by the determination of total and free fatty acids of fresh minces and matured products and lipid oxidation was evaluated by thiobarbituric acid reactive substances and cholesterol oxidation products. The increase of free fatty acids during maturation appears to be independent from processing conditions and the differences in polyunsaturated fatty acids increment found among the formulations appear to be due to inherent variations of raw materials. The presence of ascorbic acid and/or nitrite seems important for cholesterol protection and, as a consequence, for the safety of fermented meat products while spices at doses up to 0.1% do not seem to have a remarkable effect. The effect on fatty acid oxidation of the same additives and of the different processing technologies is not significantly different and the variations linked to raw material may play the greatest role. PMID- 22064146 TI - Characterisation of young bulls of the Bruna dels Pirineus cattle breed (selected from old Brown Swiss) in relation to carcass, meat quality and biochemical traits. AB - Seventy-four young bulls of the Bruna dels Pirineus beef cattle breed were reared in a typical production system and slaughtered at an average age of 381 days and live weight of 541 kg. The animals were evaluated for productive traits, carcass quality, meat quality, eating quality and biochemical characteristics of m. longissimus thoracis (LT). Biochemical measurements included intramuscular fat (IMF) and collagen proportion, haem pigment concentration, lactate dehydrogenase and isocitrate dehydrogenase activities and type I (MHC I) fibre percentage determined by ELISA. Bruna dels Pirineus bulls achieved high growth rates during the fattening period (1.63 kg/day) and showed good carcass quality, with a high dressing-out proportion (607 g/kg, hot carcass), a good conformation score (U; EUROP) and a moderate fatness score (3;1-5). Carcass composition was estimated from the sixth rib joint dissection (682 g/kg lean proportion, 127 g/kg total dissectable fat and 163 g/kg bone). IMF (24.3 g/kg) and MHC I (27.9%) showed high variabilities (CV>30%). Sensory analysis of LT included beef and livery odour and flavour intensity, and overall tenderness and juiciness assessment of loin samples (14-day ageing). Beef odour and flavour were slightly positively correlated with IMF and carcass fatness score (P<0.05). Fatness, MHC I, insoluble collagen and cooking losses tended to affect the livery flavour intensity positively. This variable was significantly higher in meat from bulls of lower carcass quality (i.e. lower conformation score, lower lean proportion; P<0.05) and higher type I fibre percentage. Loin overall tenderness and juiciness were not affected by the biochemical traits studied, however, they were negatively affected by cooking loss (P<0.05). PMID- 22064147 TI - Water properties during cooking of pork studied by low-field NMR relaxation: effects of curing and the RN(-)-gene. AB - Using low-field NMR transverse relaxation measurements, the physico-chemical state of water in meat was followed continuously during cooking of 20 uncured and 20 cured pork samples from RN-carriers (n=20) and non-carriers (n=20). The obtained relaxation data were analysed using (i) distributed exponential fitting, and (ii) principal component analysis (PCA). Distributed exponential fitting revealed transition from a system with relatively well-separated components to a less well-defined system with a wide distribution of relaxation times and merged components during cooking. In addition, distributed exponential fitting analysis implied changes in relaxation characteristics that are tentatively ascribed to denaturation of myosin and subsequent shrinkage of the myofibrillar structures. The results are further suggested to reflect formation of new compartments in the myofibrillar lattice during the shrinkage of the existing structures with a succeeding redistribution of water. Nitrite curing was found to affect the distribution of water as well as the progress in the different water populations during cooking. PCA revealed two major shifts in relaxation characteristics around 43 and 56 degrees C in uncured samples and around 43 and 63 degrees C in cured samples, and the shift around 43 degrees C was found to be significantly affected by RN-genotype. The strong shift in water properties around 43 degrees C is suggested to be a result of myosin denaturation, and thus the results imply differences in myosin denaturation in meat from RN-carriers compared with meat from non-carriers. The second shift in water properties is suggested to reflect the onset of collagen shrinkage causing longitudinal shrinkage of meat, and accordingly the shift from 56 to 63 degrees C in the presence of salt points towards an effect of curing on structural alterations during cooking. PMID- 22064148 TI - Volatiles in a sausage surface model-influence of Penicillium nalgiovense, Pediococcus pentosaceus, ascorbate, nitrate and temperature. AB - Thirty-two agar sausage models were arranged in a 2((5-1)) fractional factorial design to analyse the effects of Penicillium nalgiovense growth, Pediococcus pentosaceus starter, sodium ascorbate, sodium nitrate and temperature on 79 volatiles produced during incubation. The model focused on the outer 10 millimeters of sausages. Ascorbate addition showed clear antioxidative effects, and reduced the amount of more than half of all volatiles but increased concentrations of 2-methyl-propanal and 3-methyl-butanal. The effects of P. pentosaceus and Micrococcaceae were confounded, but together they had pronounced antioxidative effects, lowering the amount of straight chain aldehydes, 2 alkenals, furanes and ketones. P. pentosaceus and Micrococcaceae growth increased the leucine catabolites 3-methyl-butanal and 3-methyl-1-butanol. P. nalgiovense decreased the concentrations of 2-heptanone, 2-octanone and 2-nonanone, probably because of abnormally high concentration of mycelia. The data indicates that P. nalgiovense converts 2,3-butanedione and 3-hydroxy-2-butanone to 2-butanone. P. nalgiovense increased the concentrations of 1-octene-3-ol and dimethyl disulfide, liberated 2-methyl-furan and 2,4-dimethyl-furan from casing and seemed to liberate chloroform and 1,2-dimethyl benzene from meat. Both 2-methyl-1-propanol and 2-methyl-1-butanol decreased significantly with increasing temperature-this indicated a shift in metabolic pathway. No effects were seen for addition of nitrate. PMID- 22064149 TI - Effect of different feeds on meat quality and fatty acid composition of lambs fattened at pasture. AB - Two kinds of feed (commercial concentrate vs whole supplemented barley) were compared in unweaned lambs and lambs weaned at 40 days of age, fattened at pasture and slaughtered at 28 kg live weight, in order to observe their effects on meat quality and fatty acid composition. The weaning status influenced fatness; unweaned lambs displayed a greater carcass fatness score and more kidney knob and channel fat than weaned lambs. Compared with the unweaned animals, weaned lambs exhibited higher pH values at 0 h and 45 min in the m. longissimus thoracis (LT) and at 45 min and 24 h in the m. semitendinosus. The redness index (a*) of the m. LT of weaned lambs was higher than that of unweaned lambs, and lambs fed concentrate displayed a higher yellowness index (b*) and a higher Hue value than those given whole barley. Water-holding capacity did not vary with the treatments studied. The proportion of saturated fatty acids (SFA) in intramuscular fat was higher (P?0.001) in unweaned lambs than in weaned ones while, on the other hand, the latter displayed a higher proportion of monounsaturated fatty acids (MUFA) and a higher n-6/n-3 ratio in the same tissue. As was the case with intramuscular fat, the subcutaneous fat of unweaned lambs exhibited higher proportions of medium-chain fatty acids (C12:0, C14:0 y C16:0) and lower ones of stearic (C18:0) and oleic (C18:1) fatty acids than that of weaned lambs. Higher levels of heptadecenoic acid (C17:1) were found in the subcutaneous fat of lambs fed whole barley than in that of lambs given concentrate. PUFA/SFA and n-6/n-3 ratios were lower in the m. LT than in the m. quadriceps femoris. PMID- 22064150 TI - Lipid and protein oxidation in vitro, and antioxidant potential in meat from Charolais cows finished on pasture or mixed diet. AB - In this work, the effect of finishing diet (pasture- or mixed-diet) on lipid and protein oxidation in beef homogenates was evaluated. Oxidation was chemically induced by ferrous iron and hydrogen peroxide. Lipid and protein oxidation were respectively measured by determining TBA reactive substances (TBA-RS) and protein carbonyl groups (DNPH coupling method). Evaluation of the antioxidant status of meat was also performed by measuring vitamin E concentration and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase. Pasture-finishing mode of animals significantly protected lipids in meat from oxidation but diet mode did not affect protein oxidation. Concentration of vitamin E was higher in meat from pasture-fed animals. Different diets had opposite effects on SOD and GPx activities, pasture-finishing mode of animals increasing SOD activity but decreasing GPx activity. No significant effect of diet was noted on catalase activity. PMID- 22064151 TI - Fat volatiles tracers of grass feeding in sheep. AB - Volatile compounds were analysed in subcutaneous fat from lambs raised and finished on grass (GG); raised and finished on concentrates (SS); raised on grass and finished on concentrates for a long (GS1) or a short (GS2) period. Whereas 3 methylindole (skatole), a compound that has been described as a good discriminator of grass feeding, was unaffected by the diet (P>0.05), 2,3 octanedione was lower (P<0.01) in the fat from animals that spent a period in stall with a concentrate diet than in those finished on grass. Among the 20 monoterpenes detected, only p-cymene was affected by the treatment, being higher (P<0.05) in the fat from animals raised and finished on grass (GG) than in the other treatments. Eight among the 13 detected sesquiterpenes were affected by the diet treatment. In particular beta-caryophyllene, not detected in the fat from animals raised and finished on concentrates (SS group), was at basal levels in the animals raised on pasture and finished for different durations on concentrates (GS1 and GS2 treatments) and was present at high levels in the animals raised and finished on grass (P<0.0005). From a factorial discriminant analysis, four of the 33 terpenes detected discriminated perfectly those animals raised and finished on pasture (GG) from all the other groups (SS, GS1, GS2). PMID- 22064152 TI - Analysis of image-based measurements and USDA characteristics as predictors of beef lean yield. AB - This paper describes a comprehensive analysis of the 12th rib image measurements, USDA yield characteristics and USDA yield grade as predictors of beef lean yield. The predictors were used in separate groups to construct three sets of multiple linear regression models for the prediction of lean yield of 241 carcasses. Fat thickness is traditionally considered the most useful predictor. The analysis showed that the percent rib eye area was a more useful single predictor than fat thickness, and that the average fat thickness was insignificant when rib eye area and fat area were used. While marbling is traditionally considered a predictor of quality, the results showed that marbling characteristics were also useful for yield prediction. The usually-observed large differences in accuracy between the predictions of lean weight and lean percentage were shown to result from the variations in carcass weight. Statistical diagnostics confirmed the suitability of the models developed. A neural network model was tested and the results suggested that the inclusion of nonlinearity in the predictive models did not prove beneficial. Important predictors were identified and the advantages of computer vision and image processing techniques were further demonstrated. PMID- 22064153 TI - A method for early determination of meat ultimate pH. AB - A patented method of rapidly determining the ultimate pH from approximate glycolytic potential of muscles of slaughtered animals has been devised. The method is based on the rapid hydrolysis of muscle glycogen to glucose by the enzyme amyloglucosidase and subsequent measurement of the liberated glucose. In acetate buffer at pH 4.5, glucose concentration can be determined in 30 s with domestic meters for diabetes control. The meter response differed from that of glucose in blood, but was linear with concentration. In slurries comprising homogenised meat in acetate buffer and added glucose, a similar linear response was obtained. Amyloglucosidase was capable of rapidly hydrolysing glycogen to glucose in such slurries. In the 24 h following slaughter, a decrease in glycogen, as determined by glucose, occurred in parallel with the decline in pH. At the same time, lactate progressively accumulated as expected. Values for the approximate glycolytic potential and (by calibration) ultimate pH, were obtained on prerigor muscle within 7 min of muscle sampling in an industrial environment. The method is suitable for on-line application in beef abattoirs particularly those employing hot boning where ultimate must be known at the grading point. PMID- 22064154 TI - Peroxynitrite induced discoloration of muscle foods. AB - The objective of this research was to characterize the ability of peroxynitrite to cause the discoloration of meat using an in vitro oxymyoglobin system, a soluble fraction of beef muscle and minced muscle. Kinetic studies of the bolus addition of peroxynitrite (250 MUM) to solutions of oxymyoglobin in phosphate buffer showed that oxidation occurred over the first 10 min producing 180 MUM metmyoglobin and then slowed to the oxidation rate of the control. Addition of peroxynitrite (100-750 MUM) to the soluble fraction of Longissimus dorsi muscle resulted in partial to complete discoloration of samples with 500-750 MUM peroxynitrite resulting in 90-100% conversion of oxymyoglobin to metmyoglobin after 90 min. In minced L. dorsi samples, kinetic studies indicate that addition of 250 MUM peroxynitrite resulted in a longer period of metmyoglobin formation than the in vitro experiment, lasting 40 min and resulting in the formation of 280 MUM metmyoglobin. Antioxidants (ascorbic acid, glutathione, alpha-tocopherol and Trolox) were ineffective in preventing peroxynitrite-induced discoloration of minced meat, however ascorbic acid was able to partially restore color loss as the incubation period continued. The results indicate that peroxynitrite may be involved in the discoloration of muscle foods. PMID- 22064155 TI - A note on the suitability of an exponential equation to characterize pH decline corrected for muscle temperature in bovine muscle early post mortem. AB - Identifying rates of pH and temperature decline associated with bovine M. longissimus thoracis et lumborum (LTL) tenderness would assist beef carcass processors to produce a high quality product. An exponential decay equation was used to describe the early post mortem declines of pH values adjusted to 20 degrees C and their concomitant temperature data from 371 bovine LTL muscles. Approximately 10% of the muscles in the database exhibited non-exponential pH decline post mortem and the model did not converge for these muscles. For convergent muscles, the model predicted pH values homoscedastically with no significant bias. Limits of agreement analysis showed that the model predicted the adjusted pH value within 0.14 pH units. Prediction error was evenly distributed and the intra-class correlation coefficent was high (r(I)=0.98). When applied to the muscle temperature data, the exponential equation predicted temperature values heteroscedastically. These results indicated that this exponential equation characterised the post mortem pH decline in LTL muscle sufficiently well for researchers to use the exponential constant (k) of decay to describe this decline with time or muscle temperature. The equation was not appropriate for describing the decline of muscle temperature with time post mortem in this data set. PMID- 22064156 TI - Erratum to: "Comparison of the performances of Nero Siciliano pigs reared indoors and outdoors. 1. Growth and carcass composition" Meat Science 65(2) (2003) 825 831. PMID- 22064157 TI - Adipose tissue quantity and composition contribute to adipokine concentrations in the subclavian vein and the inferior mesenteric vein. AB - BACKGROUND: Adipose tissue dysfunction is associated with inflammation, type 2 diabetes mellitus and vascular diseases. Visceral adipose tissue (VAT)-derived adipokines, which are released in the portal circulation may influence liver metabolism. OBJECTIVES: (1) To estimate the contribution of VAT and subcutaneous adipose tissue (SAT) on adipokine levels by measuring differences in adipokine concentrations between the portal draining inferior mesenteric vein and the subclavian vein. (2) To determine the relation of both VAT and SAT quantity and composition to mesenteric and systemic concentrations of adipokines. DESIGN: Cross-sectional cohort study. SUBJECTS: A total of 32 patients undergoing abdominal aortic surgery. MEASUREMENTS: A panel of 18 adipokines was measured in perioperatively obtained blood samples from the subclavian vein and the inferior mesenteric vein. Adipocyte size, macrophage infiltration and capillary density were measured in subcutaneous and mesenteric adipose tissue biopsies; SAT and VAT areas were measured on computed tomography images. RESULTS: Serum interferon gamma-inducible protein 10 (IP-10) and hepatocyte growth factor (HGF) concentrations were significantly higher in the inferior mesenteric vein vs the subclavian vein. SAT area (beta -18; 95% confidence interval (CI) -35 to -2), subcutaneous adipocyte size (beta -488; 95% CI -938 to -38) and SAT macrophages quantity (beta -1439; 95% CI -2387 to -491) were negatively associated with adiponectin levels in the systemic circulation. SAT area was related to systemic concentrations of leptin. Mesenteric adiponectin concentrations were related to VAT area (beta -20; 95% CI -35 to -5) and visceral adipocyte size (beta -1076; 95% CI -1624 to -527). VAT area, adipocyte size and capillary density were related to systemic adiponectin concentrations. CONCLUSION: SAT and VAT quantities as well as morphologic characteristics of both adipose tissue depots are related to systemic and mesenteric adipokine concentrations. There were no differences in adipokine concentrations between the mesenteric and subclavian vein, except for higher IP-10 and HGF concentrations in the inferior mesenteric vein, indicating a possible contribution of VAT to IP-10 and HGF levels. PMID- 22064158 TI - Peroxisome proliferator-activated receptor alpha (PPARalpha) activation advances locomotor activity and feeding daily rhythms in mice. AB - Peroxisome proliferator-activated receptors (PPARs) are key mediators of energy homeostasis, and lipid and glucose metabolism that exhibit circadian expression. PPAR activating drugs are used clinically as lipid and glucose-lowering drugs. We evaluated the effect of long-term (11 weeks) PPARalpha and PPARgamma activation using bezafibrate and rosiglitazone, respectively, on metabolism, locomotor activity and feeding rhythms of non-obese mice. We found that bezafibrate, but not rosiglitazone, led to no weight gain and a slight weight loss with reduced epididymal fat pads. Although rosiglitazone had a minor effect on 24-h food intake rhythm, bezafibrate treatment was accompanied by increased amplitude and an advanced acrophase of the 24-h feeding rhythm. Similarly, unlike rosiglitazone, bezafibrate treatment was accompanied by a significantly advanced acrophase of locomotor activity rhythm under constant darkness conditions. As disrupted circadian rhythms lead to obesity, PPARalpha activation can serve as a clinical target for the modulation of both circadian rhythms and metabolism. PMID- 22064159 TI - Is funding source related to study reporting quality in obesity or nutrition randomized control trials in top-tier medical journals? AB - BACKGROUND: Faithful and complete reporting of trial results is essential to the validity of the scientific literature. An earlier systematic study of randomized controlled trials (RCTs) found that industry-funded RCTs appeared to be reported with greater quality than non-industry-funded RCTs. The aim of this study was to examine the association between systematic differences in reporting quality and funding status (that is, industry funding vs non-industry funding) among recent obesity and nutrition RCTs published in top-tier medical journals. METHODS: Thirty-eight obesity or nutrition intervention RCT articles were selected from high-profile, general medical journals (The Lancet, Annals of Internal Medicine, JAMA and the British Medical Journal) published between 2000 and 2007. Paired papers were selected from the same journal published in the same year, one with and the other without industry funding. The following identifying information was redacted: journal, title, authors, funding source and institution(s). Then three raters independently and blindly rated each paper according to the Chalmers method, and total reporting quality scores were calculated. FINDINGS: The inter rater reliability (Cronbach's alpha) was 0.82 (95% confidence interval = 0.80 0.84). The total mean (M) and s.d. of Chalmers Index quality score (out of a possible 100) for industry-funded studies were M = 84.5, s.d. = 7.04 and for non industry-funded studies they were M = 79.4, s.d. = 13.00. A Wilcoxon matched pairs signed-ranks test indicates no significant rank difference in the distributions of total quality scores between funding sources, Z = -0.966, P = 0.334 (two tailed). INTERPRETATION: Recently published RCTs on nutrition and obesity that appear in top-tier journals seem to be equivalent in quality of reporting, regardless of funding source. This may be a result of recent reporting of quality statements and efforts of journal editors to raise all papers to a common standard. PMID- 22064160 TI - Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men. AB - BACKGROUND: Little is known about the effects of short-term caloric restriction (CR) and overfeeding (OF) on glucose homeostasis in healthy lean individuals. In addition, it remains unclear whether the effects of CR and OF are reversed by a complementary feeding period. METHODS: Ten healthy men participated in two cycles of controlled 7-day periods of CR and refeeding (RF; protocol A), and OF and CR (protocol B) at +/-60% energy requirement. At baseline, insulin sensitivity (IS) was assessed by euglycemic clamp (M). Before and during each feeding cycle, fasting and oral glucose tolerance test-derived indices were used to estimate glucose tolerance, IS and glucose-stimulated insulin secretion. RESULTS: Clamp tests revealed normal IS at baseline (M-values 9.4+/-2.1 mg kg-1 min-1, coefficient of variation (CV)(inter) 22%). M-values were significantly correlated with indices of IS. In protocol A, CR-induced weight loss (-3.0+/-0.4 kg) was associated with an increase in fasting IS. Postprandial IS and glucose-stimulated insulin secretion remained unchanged, but glucose tolerance decreased. RF decreased fasting and postprandial IS at increased glucose-stimulated insulin secretion. In protocol B, OF significantly increased the body weight (+1.6+/-0.9 kg). Concomitantly, fasting and postprandial IS decreased at increased glucose stimulated insulin secretion. Subsequent CR reversed these effects. Inter individual variability in indices of glucose metabolism was high with coefficients of variation ranging from 9 to 59%. CONCLUSION: Significant changes in glucose metabolism are evident within 7-day periods of controlled OF and underfeeding. Although IS was impaired at the end of the CR-RF cycle, IS was normalized after the OF-CR cycle. At different feeding regimens, homeostatic responses of glucose metabolism were highly variable. PMID- 22064161 TI - Reward activity in satiated overweight women is decreased during unbiased viewing but increased when imagining taste: an event-related fMRI study. AB - OBJECTIVE: The aim of this functional magnetic resonance imaging (fMRI) study was to investigate reward-related brain activity in satiated overweight and healthy weight participants in response to high-calorie palatable food pictures, when viewing the pictures without prior instructions (called unbiased viewing) versus imagining the taste of the shown pictures (called taste imagination). We predicted that neural activation in brain reward regions would be greater in overweight participants than in healthy-weight ones and that this difference between groups would be strongest during unbiased viewing. METHOD: Neural activation was measured using fMRI in 14 overweight (mean body mass index (BMI): 29.8 kg m(-2)) and 15 healthy-weight (mean BMI: 21.1 kg m(-2)) participants who were satiated, in response to palatable and unpalatable high-calorie and low calorie food pictures, presented in an event-related design during two conditions: unbiased viewing (no prior instructions) versus taste imagination. RESULTS: A group * condition interaction was found in 14 brain regions involved in food reward processing during the presentation of high-calorie palatable food stimuli. During the taste imagination condition, neural activation in these regions was greater in the overweight participants than in the healthy-weight ones. Contrary to our expectations, the opposite pattern was observed during unbiased viewing: activation in reward regions in the overweight participants was reduced compared with the healthy-weight ones. In all brain reward regions except for the left amygdala, the group * condition interaction was specific to high calorie palatable food stimuli. CONCLUSION: Greater reward activity in the overweight participants compared with the control group when imagining taste may represent an increased reward response induced by high-calorie palatable food. During unbiased viewing, reduced reward activation in the overweight participants compared with those with a healthy weight may reflect avoidance of high-calorie palatable food stimuli. Taken together, this pattern of activation may reflect ambivalence in the overweight group between desire for (in the taste imagination condition) and avoidance of (in the unbiased viewing condition) high-calorie palatable food stimuli. PMID- 22064163 TI - Sertraline (Zoloft) response in major depressive disorder is not associated with three 5-HT1A receptor gene polymorphisms (rs6295, rs10042486, or rs1364043) in Chinese-Han patients. PMID- 22064162 TI - Genome-wide association study of comorbid depressive syndrome and alcohol dependence. AB - OBJECTIVE: Depression and alcohol dependence (AD) are common psychiatric disorders that often co-occur. Both disorders are genetically influenced, with heritability estimates in the range of 35-60%. In addition, evidence from twin studies suggests that AD and depression are genetically correlated. Herein, we report results from a genome-wide association study of a comorbid phenotype, in which cases meet the Diagnostic and Statistical Manual of Mental Disorders-IV symptom threshold for major depressive symptomatology and the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for AD. METHODS: Samples (N=467 cases and N=407 controls) were of European-American descent and were genotyped using the Illumina Human 1M BeadChip array. RESULTS: Although no single nucleotide polymorphism (SNP) meets genome-wide significance criteria, we identified 10 markers with P values less than 1 * 10(-5), seven of which are located in known genes, which have not been previously implicated in either disorder. Genes harboring SNPs yielding P values less than 1 * 10(-5) are functionally enriched for a number of gene ontology categories, notably several related to glutamatergic function. Investigation of expression localization using online resources suggests that these genes are expressed across a variety of tissues, including behaviorally relevant brain regions. Genes that have been previously associated with depression, AD, or other addiction-related phenotypes such as CDH13, CSMD2, GRID1, and HTR1B - were implicated by nominally significant SNPs. Finally, the degree of overlap of significant SNPs between a comorbid phenotype and an AD-only phenotype is modest. CONCLUSION: These results underscore the complex genomic influences on psychiatric phenotypes and suggest that a comorbid phenotype is partially influenced by genetic variants that do not affect AD alone. PMID- 22064164 TI - Mental health delivery system in India-a brief report. PMID- 22064166 TI - Dietary vitamin A concentration alters fatty acid composition in pigs. AB - This experiment was conducted to study the effect of vitamin A concentration in the diet on fatty acid composition in pigs. One-hundred and twenty eight Duroc * (Large White * Landrace) castrated male pigs were used. Pigs were randomly distributed and located in cages of four pigs each to the following treatment: vitamin A-enriched diet (100,000IU/kg) (n=16) and control diet with a basal level (7500IU/kg) (n=16). The pigs were slaughtered at an average weight of 125.9kg. No effect of diet vitamin A level on performance, carcass traits and intramuscular fat percentage was observed. The retinol concentration in subcutaneous backfat and retinol and retinol palmitate contents in liver were higher in the pigs that were given the vitamin A enriched diet than in those receiving the control diet. However the vitamin A supplementation did not increase the retinol content in the muscle. Pigs receiving the vitamin A enriched diet showed a higher C16:0 and ?SFA proportions in the outer layer and C18:0 and ?SFA proportions in the inner layer. Moreover, the diet rich in vitamin A led to a reduction of C18:1 n-9 and ?MUFA proportions in subcutaneous backfat inner layer. Dietary vitamin A concentration had not influence on main fatty acids composition of intramuscular lipids. Dietary vitamin A enrichment lead to a higher C16:0, ?SFA concentration in liver lipids. PMID- 22064167 TI - Influence of transportation stress and animal temperament on fecal shedding of Escherichia coli O157:H7 in feedlot cattle. AB - To test the influence of transportation stress and temperament on shedding of Escherichia coli O157:H7, cattle (n=150) were classified at various stages of production as Excitable, Intermediate or Calm based on a variety of disposition scores. Presence of E. coli O157:H7 was determined by rectal swabs from live animals and from colons collected postmortem. Percentage of cattle shedding E. coli O157:H7 at arrival at the feedlot was approximately equal among temperament groups. Before shipment to the processing facility, a higher (P=0.03) proportion of cattle from the Calm group shed E. coli O157:H7 compared to the other temperament groups. When pooled across all sampling periods, cattle from the Calm group had a greater percentage test positive for E. coli O157:H7. Neither the acute stressor of transportation nor a more excitable temperament led to increased shedding of E. coli O157:H7 in cattle. PMID- 22064168 TI - The effect of cooking on the fatty acid composition of longissimus muscle from beef heifers fed rations designed to increase the concentration of conjugated linoleic acid in tissue. AB - Longissimus dorsi (LD) muscle from 60 Charolais crossbred heifers, aged for 14 days was used to investigate the effect of cooking on the content of PUFA and CLA fatty acids. Animals were offered a control diet of grass silage and concentrates (CO) or rations designed to enhance the concentration of CLA in tissue, i.e. unsupplemented grazed pasture (G), sunflower-oil supplemented grazing (SFG) or linseed-oil oil supplemented grazing (LSG). The SFG diet was the most effective for increasing the concentration of CLA but also caused the highest n-6/n-3 fatty acid ratio. There were no changes in the relative distribution of fatty acids upon cooking (140 degrees C for 30min) and this procedure can be recommended because it preserves the nutritional value of the meat. It is concluded that irrespective of the change in the fatty acid composition of LD due to alteration in the diet of the cattle, cooking did not cause thermal degradation of PUFA, or thermal degradation or oxidative synthesis of CLA. PMID- 22064169 TI - Analysis and classification of commercial ham slice images using directional fractal dimension features. AB - This paper presents a novel and non-destructive approach to the appearance characterization and classification of commercial pork, turkey and chicken ham slices. Ham slice images were modelled using directional fractal (DF(0 degrees ;45 degrees ;90 degrees ;135 degrees )) dimensions and a minimum distance classifier was adopted to perform the classification task. Also, the role of different colour spaces and the resolution level of the images on DF analysis were investigated. This approach was applied to 480 wafer thin ham slices from four types of hams (120 slices per type): i.e., pork (cooked and smoked), turkey (smoked) and chicken (roasted). DF features were extracted from digitalized intensity images in greyscale, and R, G, B, L(*), a(*), b(*), H, S, and V colour components for three image resolution levels (100%, 50%, and 25%). Simulation results show that in spite of the complexity and high variability in colour and texture appearance, the modelling of ham slice images with DF dimensions allows the capture of differentiating textural features between the four commercial ham types. Independent DF features entail better discrimination than that using the average of four directions. However, DF dimensions reveal a high sensitivity to colour channel, orientation and image resolution for the fractal analysis. The classification accuracy using six DF dimension features (a(90 degrees )(*),a(135 degrees )(*),H(0 degrees ),H(45 degrees ),S(0 degrees ),H(90 degrees )) was 93.9% for training data and 82.2% for testing data. PMID- 22064170 TI - Volatile compounds in fresh meats subjected to high pressure processing: Effect of the packaging material. AB - The effect of high pressure treatment (400MPa, 10min at 12 degrees C) on the volatile profile of minced beef and chicken breast, packaged with or without aluminum foil in a multilayer polymeric bag, was investigated. The analysis of the volatile fraction was carried out by dynamic headspace extraction coupled to gas chromatography-mass spectrometry. Pressurization produced significant changes in the levels of some volatile compounds presumably coming from microbial activity. Some alcohols and aldehydes decreased, while other compounds, such as 2,3-butanedione and 2-butanone, were more abundant in high pressure processed meats. A significant migration of compounds from the plastic material was observed, mainly branched-chain alkanes and benzene compounds. Two functions built by the principal component analysis explained a high percentage of the variance and could be used to separate the samples into four distinct groups, according to high pressure treatment and packaging material. PMID- 22064171 TI - Burdizzo pre-pubertal castration effects on performance, behaviour, carcass characteristics, and meat quality of Holstein bulls fed high-concentrate diets. AB - The effects of Burdizzo pre-pubertal castration on performance, behaviour, carcass, and meat quality of Holstein bulls fed high-concentrate diets were evaluated. Two hundred bulls (8.0+/-0.42 months old) were randomly assigned to control (CTR) or Burdizzo castration (BURD). After 121d, ADG, BW, and HCW were greater in CTR animals than in BURD animals, as well as, the agonistic and sexual behaviour. However, carcass fatness and intramuscular LT (longissimus thoracis) fat percentage were greater in BURD animals than in CTR animals. Additionally, CTR animals showed lower L(*), a(*), and b(*) than BURD. The WBSF was smaller (P<0.01) in BURD than in CTR bulls at all ageing days, and in both treatments decreased (P<0.01) from 0 to 7d of ageing. Additionally, at day 0 of ageing, meat from BURD animals showed similar WBSF to meat from CTR bulls after 7d of ageing. However, 23% of BURD animals did not have a complete testicular atrophy, suggesting that the method of castration was not completely effective. PMID- 22064172 TI - National Beef Market Basket Survey - 2006: External fat thickness measurements and separable component determinations for beef from US retail establishments. AB - A market basket survey for beef retail cut composition at the retail level (four stores each from two chains in each city) was conducted in 11 US cities from January to March 2006. Beef cuts (n=17,495) were measured for external fat thickness with cuts from the chuck (0.05cm), round (0.05cm), and miscellaneous (0.04cm) having less (P<0.05) fat than cuts from the loin (0.11cm) and rib (0.11cm). Beef cuts (n=1327) were separated physically into separable components with round cuts having more (P<0.05) separable lean (96.63%) than chuck cuts (86.81%) and miscellaneous cuts (86.18%), which had more (P<0.05) separable lean than loin cuts (84.53%) with rib cuts (69.34%) having the lowest (P<0.05) separable lean. Chemical fat from the separable lean differed (P<0.05) between each cut category: round cuts (3.71%), miscellaneous cuts (4.99%), loin cuts (5.60%), chuck cuts (6.90%), and rib cuts (8.61%). Ground beef samples (n=235), with declared lean/fat percentages ranging from 73/27 to 96/4, had overall chemical fat values of 13.41% and moisture values of 67.42%. This survey documents the current beef retail cut and ground beef composition, which is helpful to those who need this information for various dietary and marketing purposes. PMID- 22064173 TI - Effects of feeding system and nitrogen source on lamb growth, meat characteristics and fatty acid composition. AB - For this study, 28 lambs were allocated to four groups: two groups were raised in stalls and fed a hay-concentrate ration. The two remaining groups were reared on dry pasture and received concentrate in stalls. In each feeding system, two iso nitrogen concentrates were used, soya bean and soya plus faba bean. At the end of the growth trial (77 days), all lambs were slaughtered. Samples of longissimus dorsi muscle were used for muscle analysis and fatty acid (FA) composition determination. Average daily gain (134g) was similar for all treatments. Stall lambs deposited significantly (p<0.001) more fat per day (13 vs 5g) and slightly more muscle (41 vs 35g) than pasture grazing ones; the first had more fat tissue (5.2kg) than the later (4.6kg). All these parameters were not influenced by nitrogen source. FA profile and meat characteristics were similar for all dietary treatments. It could be concluded that dry pasture did not affect meat quality but lead to the leaner lambs. PMID- 22064174 TI - Sodium citrate as a replacement for sodium chloride in a brine solution when evaluated in cows of different backfat thickness. AB - The objective of this study was to evaluate seven muscles from cow forequarters, which were selected based on backfat thickness; an indicator of supplemental feed before slaughter: Moderate cover (Moderate ? 0.76cm) and Thin cover (Thin ? 0.51cm). In addition, enhancement with a brine solution containing either Sodium Chloride or Sodium Citrate was evaluated for differences in shelf-life and meat quality. Moderate carcasses had increased carcass weight, increased fat cover and a lower yield for some of the muscles compared to Thin. However, there were minimal differences for palatability and shelf-life compared to Thin. Trained panelists detected minimal differences between Citrate and Chloride for palatability. Citrate resulted in visually darker steaks, but less discoloration during the display period. Results indicate that while selection of cow carcasses based upon backfat thickness results in minimal quality differences; compared to enhancement with Chloride, Citrate minimally impacts palatability and will extend product shelf-life by reducing discoloration. PMID- 22064175 TI - The value of in vivo real time ultrasonography in assessing loin muscularity and carcass composition of rabbits. AB - Sixty nine growing rabbits were scanned over the lumbar region using a real time ultrasonography (RTU) machine to estimate loin muscularity and carcass composition. Longissimus thoracis et lumborum muscle (LM) depth, width and area were taken. Animals were weighed (LW), slaughtered and carcass composition was determined. Equivalent measurements to those taken by RTU in vivo were taken on the carcass and muscularity indices were calculated on carcass and in vivo. Simple correlations between the two types of measurements were determined and carcass composition was estimated by simple and multiple regressions. The LW varied from 1200 to 3410g. The simple correlations between carcass and in vivo RTU LM measurements were high (P<0.001) and the LM area was the trait with the highest correlation (r=0.92). Simple correlations between muscularity indices measured by RTU and in carcass were significant (P<0.001). In vivo RTU measurements explained a large amount of the variation of the carcass meat weight (MW) and bone weight (r(2) range from 0.49 to 0.77; P<0.001). Using multiple regression equations to estimate carcass composition, the best fit was obtained with the LW and one or more in vivo RTU measurement. The LW explained 90.6% of the variation of MW in the carcass. In vivo RTU is able to estimate loin muscularity and carcass composition of rabbits with accuracy. The usefulness of in vivo RTU and LW to predict carcass composition of rabbits using multiple regressions was also shown. PMID- 22064176 TI - Characterization of striping in fresh, enhanced pork loins. AB - To investigate the striping phenomenon in fresh, enhanced pork, a series of experiments were undertaken to identify possible causes of the problem. No one factor (individual brine components, brine pH, ingredient concentration, enhancement pressure, meat and brine pH, or enhancement level) was specifically identified, which could be used to reduce the severity of the striping problem. Furthermore, tumbling the product for 2h, did not reduce the amount of striping, indicating once striping has occurred, it is permanent. Evaluation of the striping pattern indicates that the stripes are formed not only at the needle injection site, but also follow the muscle fiber orientation. The use of darker pork provided more of a contrast when evaluating striping, thus exacerbating the perceived level of striping. PMID- 22064177 TI - Muscle fibre characteristics of two contrasting sheep breeds: Scottish Blackface and Texel. AB - This study evaluates the effects of breed and sex, together with those of birth weight and litter size, on muscle fibre type characteristics in Texel (TEX) and Scottish Blackface sheep (SBF). The M.longissimus thoracis et lumborum (LTL) of TEX had a significantly higher total muscle cross-sectional area (16%), a higher total fibre number (20%) and a higher muscle CT density (5%) than the SBF but had a similar average muscle fibre size. The frequency of slow fibres in the LTL in TEX was lower than in SBF (7.5% vs. 9.6%). Muscle fibre histochemistry similarly demonstrated that the oxidative fibre frequency in TEX was 10% lower than in SBF. The inter-fibre lipid content in TEX was also significantly lower than in SBF. Correspondingly, TEX displayed higher frequency (91.7% vs. 90.9% in SBF) and higher relative total area (92.5% vs. 90.4% in SBF) of fast fibres. These breed differences in muscle fibre traits indicate underlying genetic variation, and future analyses will evaluate the link of these traits to meat quality and assess the usefulness of these traits in breeding programmes. PMID- 22064178 TI - Comparative study of the histochemical properties, collagen content and architecture of the skeletal muscles of wild boar crossbred pigs and commercial hybrid pigs. AB - The histochemical properties, collagen content and architecture of Musculus longissimusthoracis (LT), Musculus pectoralis profundus (PP) and Musculus biceps femoris (BF) were compared in F(1) (half blood) and F(2) (quarter blood) wild boar crossbred pigs and commercial hybrid pigs, and Japanese wild pigs. F(1) pigs showed the lowest growth rate, followed by F(2) pigs. The most rapid growth was shown by the commercial pigs. The percentage weights of LT and PP muscle to body weight were larger in the wild boar crossbred pigs than commercial pigs. The muscles of the crossbred pigs contained type I and IIA myofibers at higher frequency and type IIB at lower frequency than the commercial pigs, except for LT muscle of F(2) pigs. The myofiber diameter in each type of muscle did not differ between pigs except for the smaller type IIA in BF muscle in commercial pigs. The total amount of intramuscular collagen was less in LT muscles than the others. More intramuscular collagen was found in the wild boar crossbred pigs than the commercial pigs in LT and PP muscles. With an increase of collagen content, the perimysial collagen architecture developed but not the endomysial architecture. Traits characteristic of the crossbred pigs seem to be inherited from the wild boar. Our results clarify that cross breeding with wild boar results in pigs with distinctive muscle characteristics in terms of histochemical properties, collagen content and architecture. PMID- 22064179 TI - Polymorphism of the growth hormone gene and its association with growth traits in Boer goat bucks. AB - In the present study, the polymorphism of growth hormone (GH) gene was analyzed as a genetic marker candidate for growth traits in Boer goat bucks. Two single nucleotide polymorphisms (SNPs) - A781G (Ser/Gly35) and A1575G (Leu147), were identified by GH gene sequencing and PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) analysis. AA genotype resulted in a significant decrease in birth chest girth (P=0.03) and weaning weight (P=0.014) comparing to AB genotype, while CC genotype contributed to weaning height (P=0.04) greater than CD genotype. When in combination, AACD genotype was undesired for lower scores in a series of growth traits including body weight, length, height, and chest girth at birth and weaning, as well as the pre-weaning daily gain and body weight at age of 11 months. These results indicate that new molecular markers associated with caprine growth traits can be used in MAS (marker-assisted selection) in Boer goat bucks. PMID- 22064180 TI - Conjugated Linoleic Acid (CLA) content of meat from three muscles of Massese suckling lambs slaughtered at different weights. AB - Eighteen Massese male lambs, fed mainly maternal milk were slaughtered at 11, 14 and 17kg. Samples of Longissimus Dorsi (LD), Triceps Brachii (TB) and Semimembranosus (Sm) muscles were collected. Milk from the lamb's dams was sampled weekly. Fatty acid composition of milk and meat was determined. TB was the fattest muscle, Sm the leanest one and LD showed an intermediate value of total lipids, while the weight at slaughter did not influence total intramuscular fat content in any muscle. Although slaughter weight slightly affected overall fatty acid composition of muscles, rumenic acid and total CLA content in TB and Sm, but not in LD, significantly increased with slaughter weight. As regard milk fatty acid composition, the contents of total CLA, RA and others minor CLA isomers decreased during the first four weeks after lambing and then increased at the last control (five weeks). The animals slaughtered at a live weight of 14 and 17kg showed a greater SCD enzyme activity (estimated by product/substrate ratio) and a higher rumen activity (estimated by means of branched chain and odd chain fatty acid content in meat) than animals slaughtered at 11kg. Cis-7, trans-9 CLA content significantly increased with the slaughter age in TB and SM, while trans 7, trans-9 CLA, only increased in TB, and cis-8, cis-10 CLA, only increased in SM. Further studies are needed in order to verify weather the different behaviour of RA in LD muscle may be due to differences in muscle metabolism or fatty acid utilisation. PMID- 22064181 TI - Digestion study of proteins from cooked meat using an enzymatic microreactor. AB - A semi automatic flow procedure with photometric detection was developed for the study of meat protein digestion. This system comprised two independent flow pathways, gathered by two compartments. The gastric compartment was simulated by an ultrafiltration cell fitted with a 10 KDa cut off membrane and the intestinal compartment was simulated by a 1 KDa cut off dialysis membrane. The pathways were filled with solutions simulating digestive conditions. The proposed system was employed in digestion studies of whole protein extracts from raw and cooked (100 degrees C) meat. A mathematical modelling for the determination of the digestive kinetic constants was established. The results show that meat cooking leads to an important decrease of protein digestibility by proteases of the digestive tract. PMID- 22064182 TI - Antioxidant effect rosemary (Rosmarinus officinalis L.) and oregano (Origanum vulgare L.) extracts on TBARS and colour of model raw pork batters. AB - Herbs and spices are traditional used as food ingredients as well as for their antioxidant properties. The objective of this work was to study the concentration of carnosol, rosmarinic and carnosic acids in rosemary (Rosmarinus officinalis L.) and oregano leaves (Origanum vulgare L.), and their effect on the oxidation and colour of model pork batters. Extracts were obtained by maceration with ethanol and reflux with chloroform. Rosemary extracts showed higher antioxidant activity, even more than the phenol compounds separately. These extracts also showed the highest antioxidant capacity, possibly due to the presence of high concentrations of carnosic acid and carnosol and unidentified active compounds. However, ethanol oregano extracts containing high concentrations of phenols, mainly rosmarinic acid, efficiently prevented colour deterioration. The antioxidant effect of the studied extracts depends, not only on the concentration of phenol compounds (rosmarinic acid, carnosol and carnosic acid), but also on the extraction method and solvent. PMID- 22064183 TI - Novel association of acid phosphatase locus 1*C allele with systemic lupus erythematosus. AB - The red cell acid phosphatase (ACP1) gene, which encodes a low-molecular-weight phosphotyrosine phosphatase, has been suggested as a common genetic factor of autoimmunity. In the present study, we aim to investigate the possible association of ACP1 with the susceptibility of systemic lupus erythematosus (SLE). A total of 1,546 SLE patients and 1,947 healthy individuals from 4 Caucasians populations were included in the present study. Four single-nucleotide polymorphisms (SNPs) were genotyped in this study: rs10167992, rs11553742, rs7576247, and rs3828329. ACP1*A, ACP1*B, and ACP1*C codominant ACP1 alleles were determined using 2 of the SNPs and analyzed. After the meta-analysis test was performed, a significant association of rs11553742*T was observed (p(pooled) = 0.005, odds ratios = 1.37 [1.10-1.70]), retaining significance after multiple testing was applied (p(FDR) = 0.019). Our data indicate for first time the association of rs11553742*T with increased susceptibility in SLE patients. PMID- 22064185 TI - Prediction of drip-loss, pH, and color for pork using a hyperspectral imaging technique. AB - Many subjective grading methods with poor repeatability and tedious procedures are still widely used in meat industry. In this study, a hyperspectral-imaging based technique was investigated to evaluate its potentials for objective determination of pork quality attributes. The system extracted spectral and spatial characteristics simultaneously to determinate the quality attributes, drip loss, pH, and color, of pork meat. Six feature band images were selected for predicting the drip loss (459, 618, 655, 685, 755 and 953nm), pH (494, 571,637, 669, 703 and 978nm) and color (434, 494, 561, 637, 669 and 703nm), respectively. Two intensity indices of the band images were used as inputs to establish neural network models to predict the quality attributes. The results showed that with the hyperspectral-imaging system, the drip loss, pH, and color of pork meat could be predicted with correlation coefficients of 0.77, 0.55 and 0.86, respectively. Pork meat could be classified based on their exudative characteristics and color successfully. PMID- 22064186 TI - Effect of a new emulsifier containing sodium stearoyl-2-lactylate and carrageenan on the functionality of meat emulsion systems. AB - The emulsion capacity and stability of a new emulsifier containing sodium stearoyl lactylate plus iota carrageenan (SSL/iC) in comparison to caseinate and soy isolate was analysed. The emulsion capacity and stability of SSL/iC in oil/water (O/W) model system emulsions was higher than shown by caseinate and soy isolate. However, the O/W emulsion stability was negatively affected by sodium chloride addition, but positively affected by an increase in temperature. Meat batters were made with caseinate, soy isolate, and SSL/iC at the minimum concentration that showed a good performance (>75% stability) in the O/W emulsions. The emulsifier SSL/iC produced high cook yields and good stability when used in meat batters. However, the cooked meat batters containing SSL/iC showed texture characteristics highly detrimental to the sensory analysis. On the other hand, the addition of 2% potato starch reduced the differences in texture parameters among the samples made with the different emulsifiers. PMID- 22064187 TI - Influence of dietary conjugated linoleic acids and vitamin E on meat quality, and adipose tissue in rabbits. AB - Eighty New Zealand White rabbits, age 55 days, half male and half female, were randomly assigned to one of four diets in a 2*2*2 factorial arrangement. The diets contained 0% or 0.5% CLA, and 60 or 240mg/kg alpha-Tocopheryl acetate. Forty-eight rabbits were slaughtered at age 92 days. Growth performances and carcass weight were higher (P<0.05) in 240mg/kg of alpha-tocopheryl acetate-fed rabbits. Fat and CLA isomers content of Longissimus Lumborum (LL) muscle was higher (P<0.05) in CLA-fed rabbits than control. Fatty acid composition of LL muscle was modified (P<0.05) and oxidative stability was increased (P<0.001) by both dietary treatments. CLA increased (P<0.05) triglyceride, total cholesterol and glucose levels in plasma. Adipocytes in interscapular and perirenal fat in the 240mg/kg alpha-tocopheryl acetate and 0.5% CLA groups were larger in size but lesser in number than in 60mg/kg alpha-tocopheryl acetate and no CLA rabbit (P<0.01). PMID- 22064188 TI - Non-haem iron availability from pork meat: Impact of heat treatments and meat protein dose. AB - Pork meat heated at 60, 80, 100, and 120 degrees C (1h), raw pork meat, BSA, casein and haemoglobin were examined for their effects on in vitro iron availability measured as Fe(2+)-dialysability, and on iron-reducing capacity following in vitro protein digestion (IVPD-dialysis). The pepsin-digested samples of meat heated at 80, 100, and 120 degrees C resulted in increased in vitro iron availability. Generally, the capacity to reduce Fe(3+) to Fe(2+) was higher in the pepsin digests, whereas Fe(2+) decreased significantly after pepsin+pancreatin digestion and only part of the Fe(2+) was dialysable. Regardless of protein concentration, casein had no effect on in vitro iron availability, while pork meat protein treated at 120 degrees C showed dose dependency reaching a plateau at 50mg protein/ml. In conclusion, the major effects on iron availability in vitro was shown in pepsin digests under conditions mimicking those in the duodenal lumen and heat-treatment of meat at 120 degrees C showed the most pronounced effects. PMID- 22064189 TI - Predicting longissimus dorsi texture characteristics in beef based on early post mortem colour measurements. AB - Sixty young bulls of Pirenaica breed that were representative of the beef production and marketing systems in Northern Spain were studied. The following parameters were determined with the aim of predicting beef texture characteristics of the longissimus dorsi based on the objective measurements taken on the carcass at the early post-mortem period: colour measurement (CIE L(*)a(*)b(*)) readings were taken on the latissimus dorsi (LTD), rectus abdominis (RA), and longissimus dorsi (LD) muscles. In this study, it was observed that more information on beef tenderness is obtained with colour measurements taken on the carcass LTD and RA, and LD at 24h post-mortem. However, the regression analysis showed that beef TI from Pireanica young bulls can be predicted quite accurately by C(*) measured on the RA muscle just 45min after slaughter. PMID- 22064190 TI - Assessment of high hydrostatic pressure and starter culture on the quality properties of low-acid fermented sausages. AB - The addition of starter culture and high pressure processing after ripening improved the microbial quality of low-acid fermented sausages (fuet and chorizo). The use of Lactobacillus sakei CTC6626 and Staphylococcus xylosus CTC6013 as starter culture significantly reduced Enterobacteriaceae and Enterococcus levels in the finished sausages. Moreover, the addition of starter culture produced sausages of similar quality to traditional low-acid fermented sausages. Slightly lower pH values and higher cohesiveness were obtained for both fuet and chorizo with starter culture. Sensory analysis showed no differences between lots of chorizo whereas starter fuet was more acid and gummy. High pressure induced an additional reduction of Enterobacteriaceae in non-starter sausages. An increase of textural properties was observed after pressurization. No other differences were observed between non-treated and pressurized sausages. PMID- 22064191 TI - Comparison of the lipid content and fatty acid composition of intermuscular and subcutaneous adipose tissues in pig carcasses. AB - Lipid contents and compositions were measured in 35 pigs from seven genotype-sex groups with large variations in body composition. The animals were slaughtered at 115kg live weight, and the left side was separated into four primal cuts: belly, ham, loin, and shoulder. Samples of adipose tissues were taken from flare fat and from subcutaneous and intermuscular adipose tissues in each of the four cuts. In the loin, the outer and inner layers of subcutaneous adipose tissue were sampled separately. Total lipid content was lower in intermuscular than in subcutaneous adipose tissue. It was the highest in flare fat. There was a gradient of decreasing unsaturation from the outer layer of subcutaneous adipose tissue, to the inner layer, to intermuscular adipose tissue, to flare fat. The monounsaturated fatty acid concentrations followed the same pattern. There was a statistically positive correlation between the linoleic acid concentration of the different adipose tissues and the half carcass muscle content. PMID- 22064192 TI - The impact of sensory quality of pork on consumer preference. AB - Danish consumers from Roskilde, a town near the Danish capital Copenhagen (n=213), and from Holstebro, a provincial town in the north-western part of Jutland (n=162), rated nine different samples of pork on an unstructured hedonic scale from "do not like at all" to "like very much". The samples represented variation in raw meat quality (pH, IMF and carcass weight), muscle (LD and BF), origin (Danish/French Pay Basque), cooking method (pan/oven) and end point temperature (65 degrees C/75 degrees C). The meat was described by sensory profiling and chemical and physical analysis (pH, fat, water, colour, fatty acid composition). All the consumers preferred tender, juicy meat with a fried flavour and no off-flavours. However, within this description there were differences. The consumers from Holstebro put more emphasis on tenderness and the absence of off flavours, while the consumers in Roskilde preferred the fried flavour. The young consumers put less emphasis on tenderness, compared with consumers aged over 30 years, but preferred instead some crumbliness in the meat. A segmentation of the consumers showed that about 6% of the consumers were only influenced by flavour attributes in their preference. In contrast, 12% of the consumers were mainly influenced by texture irrespective of flavour attributes other than sour-like taste. Most of the consumers were, however, influenced by both flavour and texture as well as appearance. PMID- 22064193 TI - Influence of hunting-season stage and ripening conditions on nitrogen fractions and degradation of myofibrillar proteins in venison (Cervus elaphus) chorizo sausages. AB - The influence of hunting-season stage (deer hunted at the start versus deer hunted at the end of the season) and ripening conditions (natural versus controlled drying rooms) on nitrogen fractions and degradation of myofibrillar proteins were studied in chorizo sausages made with venison. Variations of nitrogen fractions during 21 days of ripening were found. In all batches, myofibrillar protein content decreased and proteolysis indices were between 4.6% and 14.4% at the end of ripening. However, after 45 days of storage in vacuum packs no significant variations in nitrogen fractions contents occurred. Similar changes of electrophoretic profiles of myofibrillar proteins in batches processed under controlled conditions took place during ripening, however samples of batches processed in natural drying rooms did not show the same variation. Ripening conditions influenced the relative density of bands corresponding to 45 (actin), 37 (T-troponin), 35 (tropomyosin), 20 (C-troponin) and 19kDa, after 21 days of ripening. Hunting season stage influenced the relative density of the 49kDa band after 21 days of ripening. Changes on proteins profiles were found after storage in all four batches. PMID- 22064194 TI - Effect of the Iberian*Duroc reciprocal cross on productive parameters, meat quality and lipogenic enzyme activities. AB - The aim of this study was to investigate the effect of the Iberian*Duroc reciprocal cross on: (i) productive parameters, (ii) physico-chemical traits of three muscles with different oxidative patterns (Longissimus dorsi, Biceps femoris and Psoas maior) and (iii) lipogenic enzyme activities (glucose-6 phosphate dehydrogenase and malic enzyme) in subcutaneous adipose and muscle tissues. Fourteen Duroc-sired (Duroc?*Iberian?) and 14 Iberian-sired castrate male pigs (Iberian?*Duroc?) were selected at weaning and were reared until 235 days of age. Iberian-sired pigs had significantly higher weight at slaughter (147.7kg vs. 138.8kg, p<0.05) as well as a greater ham and foreleg weight than Duroc-sired pigs. The fatty acid composition of subcutaneous adipose tissue of Duroc-sired pigs showed a higher percentage of C18:0 (13.21% vs. 14.34%, p<0.05) and a lower percentage of monounsaturated fatty acids (47.79% vs. 46.73%, p<0.05) compared to that from Iberian-sired pigs. Contrary to productive parameters, there were no noticeable differences between reciprocal cross in parameters defining meat quality, although there was a clear muscle effect on such parameters with this effect being significant for most of the traits. No differences were found between reciprocal crosses for glucose-6-phosphate dehydrogenase and malic enzymes activities in both muscular and subcutaneous adipose tissues. Lipogenic enzyme activities were considerably higher in subcutaneous adipose tissue compared to muscles. Glucose-6-phosphate dehydrogenase activity did not differ (p>0.05) between muscles, whereas malic enzyme activity was higher (p<0.05) in Psoas maior compared to Biceps femoris and those were higher than in Longissimus dorsi, which was consistent with the positive correlations (p<0.05) found between malic enzyme activity and traits defining oxidative metabolic type. On the contrary, negative correlations (p<0.05) were found between malic enzyme activity and intramuscular fat content, which could suggest that there are differences among muscles in the ability of depositing fatty acids from other tissues. PMID- 22064195 TI - Effect of dietary fat type on meat quality and fatty acid composition of various tissues in growing-finishing swine. AB - Thirty-six castrated male growing pigs were used to study the effect of dietary beef tallow (BT) versus sunflower oil (SO) on meat quality and fatty acid composition of various tissues. The diets used contained either 5% (w/w) of the variable fat source. The fat type had no significant effect on carcass traits (carcass weight, back-fat thickness, fat-lean ratio) and meat quality (colour, pH(1), pH(U), drip losses, cooking losses, shear force, sacromere length, loin moisture, loin marbling). The diet with SO instead of BT significantly increased the incorporation of polyunsaturated fatty acids in adipose tissues, loin and liver at the expense of the sum of saturated and monounsaturated fatty acids. In erythrocytes, the diet containing SO raised the contents of saturated and polyunsaturated fatty acids and lowered that of monounsaturated fatty acids. In particular, the SO diet produced an increase in the content of linoleic acid (C18:2n-6) in the various tissues. It is concluded that feeding a diet with SO instead of BT altered the fatty acid composition of tissues without simultaneously affecting various characteristics of meat quality. PMID- 22064196 TI - Quality assessment of Iberian pigs through backfat ultrasound characterization and fatty acid composition. AB - Five batches of Iberian pig backfat of different breeds and with differing feeding regimes were analysed as to their fatty acid composition and textural, thermal and ultrasonic properties. The feeding regime affected the backfat composition more than the breed of the animals. The higher the oleic acid content in the feeding regime, the higher the monounsaturated fatty acid content in the samples. Ultrasonic velocities ranged from 1609 to 1631m/s. A change in the slope of the velocity versus temperature curve was found at 6 degrees C, coincident with a change in the melting rate found in the differential scanning calorimetry. Discriminant analysis using ultrasonic measurements allowed 94.7% of the samples to be correctly classified in the batches considered, while the use of the fatty acids composition correctly classified 86.2% of the samples. Therefore, ultrasonic techniques could be useful in the characterization and classification of backfat samples from Iberian pigs. PMID- 22064197 TI - Diversity of microorganisms in the environment and dry fermented sausages of small traditional French processing units. AB - Naturally fermented sausages produced in nine traditional French processing units and their environmental surfaces were characterised by microbial and physico chemical analyses. Salmonella and Staphylococcus aureus were not detected in the environment whereas Listeria monocytogenes was detected in four samples. Staphylococcus/Kocuria, lactic acid bacteria (LAB), Enterobacteriaceae, Pseudomonas, yeasts/moulds and enterococci contaminated the surfaces of two processing units, indicating insufficient cleaning and disinfection procedures. The final sausages did not present any health risk in seven of the processing units. In two of the processing units, the final sausages were contaminated with S. aureus and L. monocytogenes, respectively, at levels exceeding the maximum tolerable limit. Staphylococcus/Kocuria and LAB grew well in the products. Biogenic amines were found in the majority of the final products. Their occurrence was associated with high numbers of lactic acid bacteria and enterococci. The study outlined the processing and microbial diversities of French naturally fermented sausages. PMID- 22064198 TI - The fate of two Listeria monocytogenes serotypes in "cig kofte" at different storage temperatures. AB - Cig kofte is a traditional Turkish food prepared from minced beef, bulgur, onions, garlic and varieties of spices. It is generally consumed within a few hours. However, leftovers can be kept in refrigerator or in room temperature up to 24h until they are consumed. In this study, survival and growth of two Listeria monocytogenes serotypes were investigated in cig kofte during the storage. For this purpose, the prepared samples were separately contaminated with serotypes 1/2b or 4b of L. monocytogenes at the level of 10(4)CFU/g and stored at 4 degrees C and 21 degrees C. L. monocytogenes colonies were counted at the beginning, 3rd, 6th, 12th and 24th hours of the storage. At 4 degrees C, L. monocytogenes 4b significantly increased (P<0.05) from 4.12 to 5.49log(10)CFU/g but L. monocytogenes 1/2b remained constant (P>0.05) during the storage period. At 21 degrees C, both L. monocytogenes 1/2b and 4b increased significantly (P<0.05) from 4.56 to 5.16log(10)CFU/g and from 4.23 to 5.65log(10)CFU/g, respectively. The physicochemical and microbiological characteristics of the cig kofte did not inhibit the growths of L. monocytogenes serotypes during the storage. These results indicated that L. monocytogenes was able to survive and grow in cig kofte at the both storage temperatures of 4 degrees C and 21 degrees C and cig kofte seemed to be a suitable medium for this pathogen. PMID- 22064199 TI - Study of the shelf life of a dry fermented sausage "salchichon" made from raw material enriched in monounsaturated and polyunsaturated fatty acids and stored under modified atmospheres. AB - The microbiological, physico-chemical and sensory properties of salchichon with high unsaturated fat content, packed under vacuum and 20/80% CO(2)/N(2) modified atmosphere, were evaluated to determine its quality changes during storage under refrigeration. These sausages were manufactured with pork meat and pork backfat obtained from pigs fed with three different diets (control diet-CO, high oleic diet-HO and high linoleic diet-HL). In general, few significant differences were found in counts of different groups of microorganism between the three types of sausages and no difference between the packaging methods. A reduction in pH values was observed during storage and no great differences were determined by storage period on water activity (a(w)). Both parameters (pH and a(w)) presented similar results to those found in different Spanish sausages and other European dry fermented products. The sensory results denoted that sensory quality gradually decreased during storage under both packaging conditions (vacuum and 20/80% CO(2)/N(2)), so it is not advisable to store longer than 150days. On the other hand, fermented sausages with high content of unsaturated fatty acids had similar sensory properties to those of conventional sausages, and even a comparable sensory stability. In conclusion, the results showed healthier salchichons (HO and HL) similar to the traditional (CO) one could be manufactured and stored under refrigeration after slicing for a reasonable period, but the advantage of the gas mixture packaging (20/80% CO(2)/N(2)) versus vacuum packaging was not clear. PMID- 22064200 TI - Selection criteria for lactic acid bacteria to be used as functional starter cultures in dry sausage production: An update. AB - Lactic acid bacteria (LAB) have long been used as starter cultures in the production of fermented dry sausages and other meat-derived commodities. These cultures are generally designed to meet food safety, shelf-life, technological effectiveness and economic feasibility criteria. Besides all these traditional properties, novel starter cultures should take into account the risks posed by the formation of biogenic amines in food, and the development and spreading of bacterial resistance to antibiotics. Further, 'functional starters' could protect consumers from harmful bacteria either by a rapid acidification or by the production of antimicrobials (bacteriocins). Specially-selected cultures may also provide probiotic benefits, and, if properly modified, they may even be endorsed with nutraceutical traits. The present review discusses the technological and new selection criteria that should be taken into account when selecting LAB starter cultures for the production of fermented dry sausages. PMID- 22064201 TI - A theoretical approach of the relationships between collagen content, collagen cross-links and meat tenderness. AB - This work concerns the relationship between meat tenderness and the rubber-like properties, i.e. pressure and elastic modulus, that endomysium and perimysium connective tissues develop when meat has been heated to a temperature above which collagen contracts. For rest length meats with similar intramuscular connective tissue morphology, and which are at the same ageing state and pH, the elastic modulus of the collagenous fraction of connective tissues is approximately proportional to the total number of collagen cross-links present per volume of meat. Calculations from various published experiments concerned with the effect on tenderness of muscle type, animal age, type, and sex from different species show that this modulus follows most of the variations of meat toughness. Moreover, the proportionality between the increase in this elastic modulus and the increase in meat toughness approaches unity in situations where toughness mainly depends on connective tissues. This work demonstrates the decisive role of rubber-like properties of connective tissues in meat tenderness variations. PMID- 22064202 TI - Dietary creatine monohydrate has no effect on pork quality of Danish crossbred pigs. AB - Creatine content in the muscle may delay postmortem lactate formation and postpone the pH decline, hence potentially improving the water-holding capacity (WHC) as shown in a previous study including purebred Duroc pigs, although the same study did not find any effect on meat from purebred Landrace pigs. In the present study Danish D(LY) crossbreeds were supplemented with 0 or 50g creatine monohydrate (CMH)/d for five days prior to the slaughter. CMH supplementation had no effect on meat quality indicators (pH and temperature), meat quality attributes (WHC and colour) or eating quality (juiciness and tenderness) of meat from the D(LY) crossbred pigs. As a consequence the D(LY) crossbreed was classified as a non-responder to CMH supplementation. PMID- 22064203 TI - A comparison of carcass and meat quality characteristics of Creole and Large White pigs slaughtered at 90kg BW. AB - The effect of breed in combination with sex (gilts or barrows) on carcass composition and meat quality characteristics were studied in two replicates involving a total of 40 Creole (CR) and 40 Large White (LW). This trial was conducted in the experimental facilities of INRA in Guadeloupe (French West Indies, 16 degrees Lat. N. and 61 degrees Long. W). All the pigs were slaughtered at about 90kg BW. No interaction between breeds and sex was found for all criteria studied. Carcass dressing weight was higher in CR than in LW (832 vs. 810g/kg, P<0.001) in connection with their lower internal organs weight (34.0 vs. 41g/kg; P<0.001). Fat cuts weight (i.e., back and leaf fat) was higher in CR than in LW (192 vs. 90g/kg; P<0.001). Creole pigs showed higher intramuscular fat percentage (IMF), higher percentage of monounsaturated fatty acids (MUFA) and lower percentage of polyunsaturated fatty acids (PUFA) in Longissimus dorsi (LD) muscle than LW pigs (4.72% vs. 2.29%, 50.2% vs. 45.0% and 7.9% vs. 13.8%, respectively). Whatever the muscle considered the ultimate pH was higher (P<0.05) in CR than in LW pigs. The drip and cooking losses of LD muscle were lower in CR than in LW (8.2% vs. 9.7% and 28.9% vs. 30.1%, respectively; P<0.05). Whatever the breed, the females were leaner than barrows (P<0.01) but the effect of sex was significant only on a few parameters. PMID- 22064204 TI - Effect of rosemary extract, chitosan and alpha-tocopherol on microbiological parameters and lipid oxidation of fresh pork sausages stored at 4 degrees C. AB - The effect of rosemary extract, chitosan and alpha-tocopherol, added individually or in combination, on microbiological parameters and lipid oxidation of fresh pork sausages stored for 20days at 4 degrees C was investigated. Microbiological determinations included the enumeration of Enterobacteriaceae, Pseudomonas spp., total viable count, yeasts and moulds and lactic acid bacteria, while pH values were also determined. Lipid oxidation was evaluated through measurement of primary (peroxide value) and secondary (malondialdehyde concentration) oxidation products. Chitosan addition resulted in significant (P?0.05) inhibition of microbial growth, while the lowest microbial counts were obtained in the samples containing both chitosan and rosemary, indicating a possible synergistic effect. Chitosan and its combinations with either alpha-tocopherol or rosemary, and especially the latter combination, showed also the most intense antioxidative effect (P?0.05), at least when compared to alpha-tocopherol alone or the controls, while use of rosemary extract alone had a comparable (P>0.05) antioxidative effect with chitosan and its combinations. Shelf life of samples containing chitosan was almost doubled compared to the remaining samples. In conclusion, the best antimicrobial and antioxidative effects were obtained from the combination of chitosan with the rosemary extract. PMID- 22064205 TI - The effect of dietary energy and vitamin E administration on performance and intramuscular collagen properties of lambs. AB - The effect of different dietary energy levels, with or without injections of vitamin E, on growth, carcass traits and intramuscular collagen (IMC) characteristics of growing lambs was studied. Twenty-four Ile de France ram lambs were evaluated in a 2*2 factorial design involving different DL-alpha-tocopheryl acetate injections (C, control=0 and V=150IU/wk, i.m. for eight wk) and energy level (N, normal=7.61 and L, low=6.47MJ/kg DM). Growth and slaughter performance, and IMC characteristics were not influenced by diet. DL-alpha-tocopheryl acetate increased ADG during suckling, while it did not affect live weight, carcass weight and dressing percentage. Vitamin E injections reduced carcass shrinkage but also had a negative effect on pelvic limb percentage. The Longissimus muscle pH values were higher in V than in C lambs. DL-alpha-tocopheryl acetate reduced IMC maturity and muscle hydroxylysylpyridinoline crosslink concentration, more markedly in lambs fed low energy diets. PMID- 22064206 TI - Effectiveness of high pressure processing on the hygienic and technological quality of porcine plasma from biopreserved blood. AB - The effects of a high hydrostatic pressure (HHP) treatment (450MPa, 15min at 20 degrees C) on both the microbiological quality and the functional properties of plasma from biopreserved porcine blood were evaluated. Blood was inoculated with Enterococcus raffinosus-PS99 (10(7)ufcmL(-1)) and stored at 5 degrees C. After 72 h storage, bacterial counts in inoculated samples decreased by 52, 70, 81 and more than 99% for coliforms, Pseudomonas spp, hemolytic and proteolytic bacteria, respectively. Counts of these bacterial groups were undetectable in the final product after pressurization, whereas total lactic acid bacteria were detected at levels up to 10(2)ufcmL(-1). Gelling, foaming and emulsifying properties of the plasma proteins were not noticeably affected by HHP. The results show that it is possible to obtain high-quality and microbiologically stable blood derivatives as functional ingredients, by combining biopreservation and HHP. PMID- 22064207 TI - Trace elements in fish and meat. PMID- 22064208 TI - Effects of duration of treatment and dosage of eicosapentaenoic acid and stearidonic acid on red blood cell eicosapentaenoic acid content. AB - OBJECTIVE: The purpose of this randomized, controlled, parallel group study was to characterize the relationships between dosages of stearidonic acid (SDA) and eicosapentaenoic acid (EPA), and incorporation of EPA into red blood cell (RBC) membranes over time. METHODS: Healthy subjects (n=131) received capsules with placebo (safflower oil), SDA (0.43, 1.3, 2.6, or 5.2 g/d) or EPA (0.44, 1.3, or 2.7 g/d) for 12 weeks. RBC fatty acids were analyzed biweekly. RESULTS: RBC %EPA increased in all EPA and SDA groups (p<0.02 vs. control) except the 0.43 g/d SDA group (p=0.187). For theoretical intakes of EPA of 0.25, 0.5, and 0.89 g/d, the amounts of SDA needed to achieve equivalent RBC EPA enrichment were 0.61, 1.89, and 5.32 g/d (conversion efficiencies of 41%, 26%, and 17%), respectively. CONCLUSIONS: SDA increased RBC %EPA in a dosage and time-dependent manner at intakes as low as 1.3 g/d. PMID- 22064209 TI - Psychological factors associated with visual impairment. AB - An attempt has been made to study the psychological pattern in terms of six criteria in the visually handicapped subjects. A total of 75 subjects were administered Cornell Medical Index health questionnaire. Twenty-five out of these had normal vision, another third had curable ocular disease and the rest were permanently handicapped. PMID- 22064210 TI - Comparative pharmacophysiology of vernakalant, ranolazine, and d-sotalol in canine pulmonary vein sleeve preparations: new flavors or same old taste? PMID- 22064211 TI - Developmentally regulated SCN5A splice variant potentiates dysfunction of a novel mutation associated with severe fetal arrhythmia. AB - BACKGROUND: Congenital long-QT syndrome (LQTS) may present during fetal development and can be life-threatening. The molecular mechanism for the unusual early onset of LQTS during fetal development is unknown. OBJECTIVE: We sought to elucidate the molecular basis for severe fetal LQTS presenting at 19 weeks' gestation, the earliest known presentation of this disease. METHODS: Fetal magnetocardiography was used to demonstrated torsades de pointes and a prolonged rate-corrected QT interval. In vitro electrophysiological studies were performed to determine functional consequences of a novel SCN5A mutation found in the fetus. RESULTS: The fetus presented with episodes of ventricular ectopy progressing to incessant ventricular tachycardia and hydrops fetalis. Genetic analysis disclosed a novel, de novo heterozygous mutation (L409P) and a homozygous common variant (R558 in SCN5A). In vitro electrophysiological studies demonstrated that the mutation in combination with R558 caused significant depolarized shifts in the voltage dependence of inactivation and activation, faster recovery from inactivation, and a 7-fold higher level of persistent current. When the mutation was engineered in a fetal-expressed SCN5A splice isoform, channel dysfunction was markedly potentiated. Also, R558 alone in the fetal splice isoform evoked a large persistent current, and hence both alleles were dysfunctional. CONCLUSION: We report the earliest confirmed diagnosis of symptomatic LQTS and present evidence that mutant cardiac sodium channel dysfunction is potentiated by a developmentally regulated alternative splicing event in SCN5A. Our findings provide a plausible mechanism for the unusual severity and early onset of cardiac arrhythmia in fetal LQTS. PMID- 22064212 TI - The genetics of dilated cardiomyopathy. PMID- 22064213 TI - Health care transitions: a peek into the future. PMID- 22064214 TI - Hypoglycemia: symptom or diagnosis? PMID- 22064215 TI - Entrapment of mycelial fragments in calcium alginate: a general technique for the use of immobilized filamentous fungi in biocatalysis. AB - Transformation reactions on 3beta,17beta-dihydroxyandrost-5-ene using free fungal cells were compared with those carried out by macerated mycelia, immobilized in calcium alginate beads. Six fungi were utilized in this study, namely Rhizopus oryzae ATCC 11145, Mucor plumbeus ATCC 4740, Cunninghamella echinulata var. elegans ATCC 8688a, Aspergillus niger ATCC 9142, Phanerochaete chrysosporium ATCC 24725 and Whetzelinia sclerotiorum ATCC 18687. The results show, for the first time, that encapsulated mycelial fragments essentially carry out the same bioconversions as those observed with growing cells. As the immobilized cells were "resting", the products formed were free of contamination by natural products, and this greatly aided the purification of the metabolites. Conditions for bead preparation were optimized. Furthermore, it was noted that the beads could be reused, once they had been subjected to a rejuvenation process. PMID- 22064216 TI - Brassinosteroids and analogs as neuroprotectors: synthesis and structure-activity relationships. AB - We have demonstrated previously that the brassinosteroid (BR) 24-epibrassinolide exerts neuroprotective effects deriving from its antioxidative properties. In this study, we synthesized 2 natural BRs and 5 synthetic analogs and analyzed their neuroprotective actions in neuronal PC12 cells, against 1-methyl-4 phenylpyridinium (MPP(+)), a neurotoxin known to induce oxidative stress and degenerescence of dopaminergic neurons characteristic of Parkinsonian brains. We also tested the neuroprotective potential of 2 commercially available BRs. Our results disclosed that 6 of the 9 BRs and analogs tested protected neuronal PC12 cells against MPP(+) toxicity. In addition, our structure-activity study suggests that the steroid B-ring and lateral chain play an important role for their neuroprotective action. PMID- 22064217 TI - Synthesis of 21-nitrogen substituted pregna-5,17(20)-dienes from pregnenolone. AB - The facile synthesis of six [17(20)Z]- and [17(20)E]-isomeric 3beta-hydroxy pregna-5,17(20)-dien-21-oyl amides and three [17(20)E]-3beta-hydroxy-2-[prergna 5,17(20)-dien-20-yl]-oxazolines from pregnenolone is presented. The synthetic scheme consists of transformation of pregnenolone into the known 17alpha-bromo-21 iodo-3beta-acetoxypregn-5-en-20-one followed by reaction with ethanolamine, 2 methyl-2-aminopropanol, and (1-aminocyclohexyl)methanol resulted in mixture of [17(20)E]- and [17(20)Z]-pregna-5,17(20)-dien-21-(2-hydroxy)-oyl amides; separation of [17(20)E]- and [17(20)Z]-isomers; their cyclization into [17(20)E] oxazolines under action of POCl(3) in pyridine, and removal of acetate protecting groups. Significantly different orientation of nitrogen containing substituents in [17(20)Z]- and [17(20)E]-isomers regarding to steroid backbone enables their configuration to be easily identified by NMR spectroscopy. All synthesized compounds did not exhibit marked toxic effects in three cell lines (MCF-7, Hep G2, and LNCaP). In androgen-sensitive LNCaP cells all testing compounds at concentrations of 50 nM potently stimulated proliferation. PMID- 22064218 TI - Redetermination of despujolsite, Ca(3)Mn(SO(4))(2)(OH)(6).3H(2)O. AB - The crystal structure of despujolsite [tricalcium manganese bis-(sulfate) hexahydroxide tri-hydrate], the Ca/Mn member of the fleischerite group, ideally Ca(3)Mn(4+)(SO(4))(2)(OH)(6).3H(2)O, was previously determined based on X-ray diffraction intensity data from photographs, without H-atom positions located [Gaudefroy et al. (1968 ?). Bull. Soc. Fr. Mineral. Crystallogr.91, 43-50]. The current study redetermines the structure of despujolsite from a natural specimen, with all H atoms located and with higher precision. The structure of despujolsite is characterized by layers of CaO(8) polyhedra (m.. symmetry) inter-connected by Mn(OH)(6) octa-hedra (32. symmetry) and SO(4) tetra-hedra (3.. symmetry) along [001]. The average Ca-O, Mn-O and S-O bond lengths are 2.489, 1.915, and 1.472 A, respectively. There are two distinct hydrogen bonds that stabilize the structural set-up. This work represents the first description of hydrogen bonds in the fleischerite group of minerals. PMID- 22064219 TI - Colour of muscle from 18-month-old steers given long-term daily exercise. AB - Darker beef from pasture-fed compared with grain-fed cattle may result from differences in physical activity rather than differences in nutrition. The objective was to determine if steers that were exercised produced darker meat than non-exercised steers and whether any effect was muscle-related. Exercised steers were walked 4.41 km daily in a single bout, six days per week for 18 weeks at an average speed of 5.2 kmh(-1). All steers were fed grass silage on an ad libitum basis plus 6 kg concentrates. Following slaughter, muscle colour coordinates ('L' (lightness), 'a' (redness) and 'b' (yellowness) values) of M. longissimus dorsi (LD), M. semimembranosus (SM) and M. extensor carpi radialis (ECR) were recorded at 48 h postmortem and redness and yellowness were used to calculate muscle hue ('H') and colour intensity/saturation ('C'). The pH of all muscles was measured at 1.5, 3, 6, 22 and 48 h postmortem and LD samples were recovered (90 min postmortem) for glycolytic potential (GP) assessment. Exercise did not affect muscle lightness, yellowness, hue or colour intensity. However, LD was the darkest (P<0.001) and SM the most saturated (P<0.001) muscle. Exercise affected muscle redness in a muscle-dependent manner (muscle*exercise, P=0.038) whereby ECR became more red with exercise but LD and SM were unaffected. There were muscle*time (P<0.001) and time*exercise (P=0.045) interactions for muscle pH. The ECR muscle had the highest pH at all times. The exercised steers had higher (P<0.05) LD muscle pH than control steers at 3 and 6 h postmortem. Exercise did not affect myoglobin concentration, which was muscle dependent, decreasing in the order: SM (6.72 mg/g)>ECR (6.33 mg/g)>LD (5.48 mg/g), which were all different (P<0.001). Exercise had no effect on GP in LD muscle (111 vs. 99 MUmol/g for control and exercised steers, respectively; SED=6.6 MUmol/g). It was concluded that although application of exercise did not affect muscle lightness and thus, did not cause 'darker' meat, it did affect muscle redness in a muscle-dependent manner. PMID- 22064220 TI - Development of a PCR-culture technique for rapid detection of yeast species in vacuum packed ham. AB - A rapid assay for detection of yeast species in vacuum packed ham has been developed based on the polymerase chain reaction (PCR) coupled to a 24 h pre enrichment at 25 degrees C. DNA was isolated from yeast inoculated ham samples and amplified using primers specific for the 18S rRNA gene sequences of yeasts. A detection limit of 10(2) CFU/cm(2) was achieved following enrichment of samples experimentally inoculated with three yeast species frequently associated with meat products spoilage: Debaryomyces hansenii, Yarrowia lipolytica, and Kluyveromyces marxianus. Likewise, commercial sliced and vacuum packed ham samples were analysed using the PCR-culture technique. The results obtained in this work show that PCR amplification of a conserved region of the 18S rRNA gene in the yeast species could be potentially used as a rapid tool for detection of low levels of viable spoilage yeasts in meat products. PMID- 22064221 TI - The effect of whey protein-enriched fractions on the physical and sensory properties of frankfurters. AB - Four Beta-lactoglobulin (beta-lg) enriched fractions containing different mineral contents were prepared and evaluated in frankfurters. Frankfurters were assessed for cook loss, water holding capacity (WHC), textural and sensory characteristics. The addition of the beta-lg fractions reduced the cook loss (p<0.001) in comparison to the control (6.63% vs 3.98%). The fractions (beta-lg 1 and 2) with the lowest calcium level significantly reduced WHC (p<0.01). The beta lg fractions had no detrimental effect on the sensory characteristics (p>0.05). All of the fractions increased the TPA value of hardness in comparison to the control (p<0.001) while the springiness decreased in the fractions (p<0.001) with the lowest mineral level. This study showed that the mineral composition of the beta-lactoglobulin fractions affected cook loss, tenderness and hardness (TPA) of the frankfurters and the addition of the beta-lactoglobulin enriched fraction did not affect the organoleptic quality of frankfurters in comparison to the control. This study shows the potential for next generation whey protein fractions and their application in meat products. PMID- 22064222 TI - Effects of carcass weight and muscle on texture, structure and myofibre characteristics of wild boar meat. AB - Texture, histology and muscle fibre characteristic of selected muscles: m. quadriceps femoris (QF), m. biceps femoris (BF), and m. semimembranosus (SM) of wild boars of different carcass weight (20+/-2 and 60+/-3kgSD) were compared. Muscle texture (hardness, cohesiveness, springiness, chewiness) was determined with the double penetration test performed with the Instron 1140 apparatus. Structural elements (muscle fibre cross-section area, perimysium and endomysium thickness) and percentage of myofibres of each type: I (slow oxidative), IIA (fast oxidative-glycolytic) and IIB (fast glycolytic) per muscle fibre bundle, were measured in muscle samples using a computer image analysis program. The young wild boar muscles showed significantly lower values for the textural parameters (p<0.05). The muscle fibre cross-sectional areas of the juvenile wild boar muscles were significantly lower and the perimysium and endomysium thinner (p<0.05) than those in the old wild boar meat, while the percentage of type IIB fibres was higher. Of all the wild boar muscles tested, the highest hardness and chewiness values were found in BF which, at the same time, showed the highest fibre cross-sectional area and the thickest perimysium and endomysium. The highest percentage of I and IIA fibre types was typical of BF and SM either in young or in old wild boars with the lowest percentage of type I and the highest percentage of type IIB fibres being found in the QF. The results suggest that a higher hardness of wild boar muscles can be connected with a thicker perimysium and endomysium, fibres of higher cross-sectional area and probably a higher content of red fibres (type I). PMID- 22064223 TI - Microbiological and sensory changes in "Morcilla de Burgos" preserved in air, vacuum and modified atmosphere packaging. AB - "Morcilla de Burgos" is the most popular blood sausage in Spain. Traditionally, this product is distributed and sold without packaging in the local market. To extend its shelf-life and expand the market, different packaging methods have been employed and compared: "morcilla" stored in air (without packaging), in vacuum and in modified atmosphere packaging (MAP) using three different CO(2) concentrations 30%, 50% and 80% and balanced with N(2). Total viable count (TVC), psychrotrophs, lactic acid bacteria (LAB), pseudomonads, enterobacteria, moulds and yeasts, enterococci, Staphylococcus aureus, and sulfite reducing clostridia were analysed during storage at 4 degrees C. Sulfite-reducing clostridia, pathogenic staphylococci, and enterococci were not detected in any sample. In air stored "morcilla" a significant increase in all microbial groups was observed during storage. Pseudomonads were the predominant microorganisms reaching a population higher than 8 log cfu/g after 27 days of storage. On the other hand, a decrease in pH was noticed in MAP and in vacuum packaged "morcilla" (pH 4.73) during storage. At the same time, LAB becomes the predominant species in all these packaged samples. The rest of the microbiota did not grow during storage. In "morcilla" packed with 50% and 80% of CO(2), counts of pseudomonads and enterobacteria were lower than found in the vacuum packs. Sensory analysis showed that shelf-life of "morcilla" stored in air did not exceed 17 days, while samples packed under vacuum and with 30% CO(2) were acceptable until 22 days of storage. "Morcillas" packaged with 50% and 80% CO(2) were sensorially acceptable for 32 days. PMID- 22064224 TI - Fatty acid composition of meat from typical lamb production systems of Spain, United Kingdom, Germany and Uruguay. AB - The fatty acid composition of commercial lambs from different production systems of Spain, Germany, United Kingdom and of two types of Uruguayan lambs (heavy and light) was studied. Concentrate fed lambs, as Spanish lambs, displayed the highest proportions of linoleic acid (C18:2), while Uruguayan lambs, reared under extensive grazing conditions, showed the highest proportions of linolenic acid (C18:3), due to the great concentration of this fatty acid in grass. German and British lambs, which were fed grass and concentrate, displayed intermediate proportions of linolenic acid (C18:3). Heavy Uruguayan lambs had higher intramuscular fat content (5.92%) than German (4.25%) and British (4.32%) lambs, and this content was twofold higher than light lambs (Spanish (2.41%) and light Uruguayan (3.05%)). Heavy Uruguayan, German and British lambs had a low polyunsaturated/saturated (P/S) ratio due to their high saturated fatty acid (SFA) content and proportion. Principal component analysis was performed to study the relationship between fatty acids. Spanish lambs were clearly separated from the other types and were situated close to the proportions of short chain and n-6 fatty acids and n-6/n-3 ratio in the data plot for fatty acid proportions. Light Uruguayan lambs were located close to long chain fatty acids, and heavy Uruguayan and British lambs were placed near the antithrombotic potential (ATT), stearic acid (C18:0), SFA and conjugated linoleic acid (CLA) proportions. German lambs were located between Spanish lambs and the other types. PMID- 22064225 TI - Effects of enhancement with varying phosphate types and concentrations, at two different pump rates on beef biceps femoris instrumental color characteristics. AB - The effect of enhancing beef biceps femoris muscles (n=45) with solutions comprising 2.0% sodium chloride and either sodium hexametaphosphate (SHMP), sodium tripolyphosphate (STPP), or tetrasodium pyrophosphate (TSPP) at either 0.2% or 0.4% of product weight on instrumental color during simulated retail display was investigated. All solutions were injected into muscle samples at either 112% (12% pump) or 118% (18% pump) of raw product weight. Muscles treated with all three phosphate types had lower (P<0.05) L* and b* values compared to untreated muscles (CNT). Steaks enhanced with STPP had similar (P>0.05) a* values as CNT, whereas SHMP- and TSPP-treated steaks generally had lower a* values than CNT. Across phosphate type, excluding day 3 of display, steaks treated with phosphate at 0.4% had similar (P>0.05) a* values as CNT, whereas those with 0.2% phosphate addition had lower (P<0.05) a* values than CNT. Across five days of display, STPP maintained higher (P<0.05) a* values than steaks treated only with sodium chloride, whereas SHMP did not differ (P>0.05) from sodium chloride treated steaks. While STPP maintained a similar (P>0.05) saturation index as CNT, SHMP and TSPP generally had decreased (P<0.05) vividness during display. Additionally, excluding day 3 of display, phosphate concentration at 0.4% maintained similar vividness as CNT, whereas 0.2% phosphate concentration caused decreased (P<0.05) vividness, compared to CNT. The 630/580nm ratio results indicated that SHMP had less (P<0.05) oxymyoglobin than CNT throughout display. Disregarding day 3 of display, both STPP and TSPP had similar (P>0.05) oxymyoglobin proportions as CNT. These results indicate that STPP was the most effective phosphate type for maintaining color. Additionally, 0.4% phosphate concentrations can maintain color better than 0.2% phosphate concentrations. However, none of the phosphate/salt combinations produced superior color, compared to untreated steaks. PMID- 22064226 TI - The effect of alpha-tocopherol and butylated hydroxyanisole on the colour properties and lipid oxidation of kavurma, a cooked meat product. AB - Kavurma is a cooked meat product and is consumed sliced. The amount of animal fat in kavurma (30-40%) is higher than in other meat products; therefore, lipid oxidation and colour defects are a major problem during storage and in the market place. To preserve the quality characteristics of kavurma in markets antioxidants must be added and the product must be packaged and stored at low temperature. In this study, the effects of alpha-tocopherol and butylated hydroxyanisole (BHA) levels on lipid oxidation and colour deterioration of sliced and vacuum-packaged kavurma were investigated. Kavurma was made from beef meat and melted beef fat in 5 groups: No-added antioxidant, 50mg/kg BHA, 100mg/kg BHA, 50mg/kg alpha tocopherol and 100mg/kg alpha-tocopherol. The kavurma produced was sliced (3-4-cm thick) and vacuum packed and stored at 4 degrees C for 300 days, and thiobarbituric acid reactive substance, pH, moisture, lightness, redness and yellowness values of sliced product were determined during storage. The use of antioxidants in kavurma production caused a significant (P<0.01) decrease in the thiobarbituric acid reactive substances (TBARS) values. The lipid oxidative stability effect of the antioxidants was in following order: 100mg/kg BHA>100mg/kg alpha-tocopherol>50mg/kg BHA=50mg/kg alpha-tocopherol>no-added antioxidant group. Also, TBARS values did not differ significantly (P>0.05) between 0 and 300 days in the 100mg/kg BHA and 100mg/kg alpha-tocopherol groups. In addition, the no-added antioxidant group had lower lightness and yellowness values than all the antioxidant groups. Sliced and vacuum-packaged kavurma with added antioxidant showed greater colour and lipid oxidative stability during storage than kavurma to which no antioxidant was added. PMID- 22064227 TI - Instrumental colour of Iberian ham subcutaneous fat and lean (biceps femoris): Influence of crossbreeding and rearing system. AB - The influence of crossbreeding (Iberian vs Iberian*Duroc 50% pigs) and rearing system (Montanera vs Pienso) on the instrumental colour of Iberian ham (subcutaneous fat and biceps femoris muscle) and the relationships to sensory appearance and chemical composition were researched by using a factorial design. In subcutaneous fat, a significant effect (p<0.05) of crossbreeding and rearing system was found: b* and chroma were larger in hams from Iberian pigs than from Iberian*Duroc (50%) pigs, and L*, a* and chroma were larger in Pienso hams than in Montanera hams. CIEL*a*b* variables of subcutaneous fat were closely related to subcutaneous fatty acid composition, the largest correlationships involving L* (L* and 18:0, 0.652, p<0.001; L* and 18:1, -0.616, p<0.001). Instrumental colour variables and sensory appearance were also correlated (L* and fat pinkness, 0.539, p<0.001). In lean (biceps femoris), instrumental colour data was not affected by crossbreeding and rearing system. CIEL*a*b* variables were not related to chemical composition (moisture, NaCl, intramuscular fat and pigment content), although they were correlated to sensory appearance (L* and marbling, 0.419, p=0.014). PMID- 22064228 TI - Changes in flavor compounds of dry-cured Chinese Jinhua ham during processing. AB - Sixty experimental Jinhua hams were processed by a traditional method using green hams from local Liangtouwu cross-bred pigs. Samples of Biceps femoris were taken from five hams randomly at each of the key stages of production, i.e., green ham, end of salting, end of sun-drying, middle of loft-aging, end of loft-aging, post aging-1 and post-aging-2. Analysis of flavor compounds showed 89 compounds at the green ham stage and at the end of salting, 90 at the end of sun-drying, 91 at the middle of loft-aging, 96 at the end of loft-aging, 93 at the post-age-1 and 94 at the post-age-2. The flavor compounds could be clustered in the following chemical families: alkanes and alkenes, aromatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids, esters, oxygenous heterocycle compounds, nitrogenous compounds, sulphur compounds, chloride compounds, amides, and terpenes. During processing, the concentrations of aldehydes and carboxylic acids increased; while the concentrations of alcohols, ketones, alkanes, alkenes, aromatic and cyclic hydrocarbons decreased. Sulphur compounds and pyrazines were formed and increased continuously during processing. In the final Jinhua ham, the contents of aldehydes, carboxylic acids, alcohols and ketones were 45.07%, 18.39%, 13.93% and 9.00% of the total flavor substances, respectively. The first principal component was a group dominated by five unbranched aldehydes; the second principal component was a group dominated by five branched and unbranched alcohols, two branched ketones, toluene, hexane and 4-nitrophthalamide. The two principal components explained 90.6% of the total flavor variance in Jinhua ham. PMID- 22064229 TI - Quality characteristics of irradiated turkey breast rolls formulated with plum extract. AB - The effects of adding 1%, 2% and 3% plum extract on the quality characteristics of vacuum-packaged, irradiated ready-to-eat turkey breast rolls were determined. Turkey breast rolls were sliced, packaged and irradiated at 0 or 3 kGy using a Linear Accelerator. Lipid oxidation, volatile profiles, color, texture, proximate analysis and sensory characteristics of sliced turkey breast rolls were determined at 0 and 7 days of storage. Addition of plum extract had no detectable effect on the proximate analysis of turkey breast rolls. Plum extract increased a* and b* values, and decreased L* value of turkey breast rolls due to the original color of plum extract. Addition of >2% plum extract to turkey breast rolls was effective in controlling lipid oxidation of irradiated meat and the production of aldehydes (hexanal, heptanal, octanal, and nonanal) in non irradiated meat at Day 0. Texture of turkey breast rolls was not influenced, but juiciness was increased by plum extract. Therefore, addition of 3% or higher of plum extract is recommended to improve mouth-feel and antioxidant effect in irradiated turkey breast rolls. However, the color of turkey breast rolls with 3% plum extract was dark and might not be appealing to consumers. PMID- 22064230 TI - Effects of dietary alpha-lipoic acid on glycolysis of postmortem muscle. AB - The effects of dietary alpha-lipoic acid (alpha-LA) on the pH value, AMP activated protein kinase (AMPK) activation, and the activities of glycogen phosphorylase and pyruvate kinase in postmortem muscle were investigated. Eighteen C57BL/6J mice were fed diets containing 0%, 0.5%, and 1.0% alpha-LA. At the end of 2-week feeding trial, the mice were killed and longissimus muscles were sampled at 0-, 1-, and 24-h postmortem for pH determination and enzyme assay. The results showed that dietary alpha-LA treatment significantly slowed down the decrease of pH values in postmortem muscle. The ultimate pH values in postmortem muscle of mice receiving 0.5% and 1.0% alpha-LA treatments were 6.40 and 6.63, respectively, significantly higher than that (6.21) of no alpha-LA treatment (p<0.05). AMPK was activated at the early postmortem stage. Dietary alpha-LA can suppress the activation of AMPK in postmortem muscle. At 1- and 24-h postmortem, activities of AMPK were much lower in postmortem muscle of mice receiving 0.5% and 1.0% alpha-LA treatments than that with no alpha-LA treatment. Between these two dietary alpha-LA treatments, however, no difference in AMPK activity was observed, indicating that 0.5% dietary alpha-LA is enough to suppress AMPK in postmortem muscle. Similar to AMPK, glycogen phosphorylase activity was higher in the treatment without dietary alpha-LA than those with 0.5% and 1.0% dietary alpha-LA supplements. No difference in the activity of glycogen phosphorylase was observed between the 0.5% and 1.0% dietary alpha-LA treatments. Dietary alpha-LA had no significant influence on the activity of pyruvate kinase in postmortem muscle. All these results indicate that AMPK plays a role in glycolysis in postmortem muscle. Dietary alpha-LA supplementation can suppress the activation of AMPK in postmortem muscle, down-regulate the activity of glycogen phosphorylase, resulting in a higher ultimate pH values in postmortem muscle. Therefore, dietary alpha-LA supplementation is a potential way to reduce the incidence of pale, soft, exudative (PSE) meat. PMID- 22064231 TI - Utilization of hazelnut pellicle in low-fat beef burgers. AB - Hazelnut pellicle was used as a dietary fiber in the production of beef burgers. The effects of hazelnut pellicle addition on proximate composition, pH, cook loss, dimensional changes, color and sensory characteristics of beef burgers were evaluated. Hazelnut pellicle addition affected some quality parameters of beef burgers. The control samples had the lowest moisture and protein contents (P<0.05). The cooking yield and reduction in diameter and thickness of beef burgers improved by the addition of hazelnut pellicle. Beef burgers formulated with hazelnut pellicle had lower L, a and b values than control samples (P<0.05). There were differences among beef burger samples in respect to sensory properties, control samples and 1% and 2% pellicle added samples had high acceptability. The results indicate that, 1-2% hazelnut pellicle can be used as a suitable dietary fiber source in low-fat beef burger production. PMID- 22064232 TI - Effect of feeding on fatty acid composition of muscles and adipose tissues in young goats raised in the Argan tree forest of Morocco. AB - The characteristics of meat from goats raised in the Argan tree forest in the south-western part of Morocco were studied in two experiments. Each experiment was carried out on three groups of six male goats. They were reared either indoors (IC) and fed concentrate or outdoors where they grazed in the Argan tree forest and were offered concentrate (OC) or only Argan fruit pulp (OS). Outdoor raised goats had a very low growth rate in the first experiment (34 g/d), whereas it was relatively high in the second experiment (64 g/d) in which herbaceous vegetation availability was higher. In each experiment, omental (OM) and perirenal (PR) weights were the lowest in the two groups of goats raised outdoors. Lipid and cholesterol contents in muscles were lower in goats raised in the Argan tree forest than in those raised indoors. Outdoor-raised goats had particularly high proportions of odd-chain fatty acids (FA), branched-chain (FA) of the iso and anteiso series in adipose tissues and muscles and higher n-6 and n 3 polyunsaturated FA (PUFA) proportions and a lower n-6:n-3 PUFA ratio than indoor-raised goats. Indoor-raised goats had a higher proportion of palmitic acid and a lower proportion of archidic acid than outdoor-raised goats. In indoor raised goats, the proportions of Delta9 straight-chain mono-unsaturated fatty acids (MUFA) (C(16:1n-7) and cis C(18:1n-9)) were relatively higher than those of total MUFA, because of lower percentages of some MUFA, such as C(16:1n-9) and other isomers of oleic acid. The low fat content and FA profile of the meat from the goats reared in the Argan tree forest conveyed beneficial characteristics to this meat in regards to human health. The relatively high contents of branched chain FA of iso and anteiso series and PUFA in the meat from goats raised in the Argan tree forest could be considered as a sign of typicity. PMID- 22064233 TI - Application of electrolyzed oxidizing water to reduce Listeria monocytogenes on ready-to-eat meats. AB - Experiments were conducted to determine the effectiveness of acidic (EOA) or basic electrolyzed oxidizing (EOB) water, alone or in combination, on ready-to eat (RTE) meats to reduce Listeria monocytogenes (LM). Frankfurters or ham surfaces were experimentally inoculated with LM and subjected to dipping or spraying treatments (25 or 4 degrees C for up to 30 min) with EOA, EOB, and other food grade compounds. LM was reduced the greatest when frankfurters were treated with EOA and dipped at 25 degrees C for 15 min. A combination spray application of EOB/EOA also resulted in a slight reduction of LM on frankfurters and ham. However, reductions greater than 1log CFU/g were not observed for the duration of the study. Even with a prolonged contact time, treatments with EOA or EOB were not enough to meet regulatory requirements for control of LM on RTE meats. As such, additional studies to identify food grade antimicrobials to control the pathogen on RTE meats are warranted. PMID- 22064234 TI - Extraction of meat juices for isotopic analysis. AB - So far no standard procedure exists to obtain water of meat for isotopic (18)O/(16)O-water analysis. Fast extraction via heating the tissues is possible when considering certain boundary conditions. A specially designed vessel was tested with water and was then used for meat juice extraction. The reproducibility (sigma) of delta(18)O-values was 0.120/00. Meat samples of six different species were analysed. Water of pork samples was extracted after open storage. Here, decreases in meat weight correspond to decreases in extract yield and to an increase in the (18)O/(16)O-ratio. The mean water contents in extracts was almost constant [93.2+/-0.05 wt% (p>0.05)]. The technique offers an opportunity to develop an automatic, mobile extraction device and to obtain extracts with no further influences on their quality. This method could also be useful for the determination of meat quality attributes as cooking loss or drip without evaporative losses. PMID- 22064235 TI - Myosin heavy chain isoform composition influences the susceptibility of actin activated S1 ATPase and myofibrillar ATPase to pH inactivation. AB - The objectives of this study were to determine the influence of pH and MyHC isoforms on myofibrillar and actin-activated myosin subfragment 1 (S1) ATPase activity and the protective effect of actin. Red (RST) semitendinosus and white (WST) semitendinosus myofibrils were incubated at pH 7, 6, or 5.5 with 0 or 2mM ATP. RST and WST S1 isolates were incubated at pH 7, 6, or 5.5 in the presence or absence of actin. Maximum calcium-activated myofibrillar and actin-activated S1 ATPase activity were then assayed at pH 7. Incubation of myofibrils with ATP caused ATPase activity of myofibrils to decrease (p<0.05) with the pH of the incubation. RST myofibrils maintained a higher (p<0.0001) relative activity than WST myofibrils after incubation at pH 6 with ATP. Myofibrils incubated without ATP exhibited higher (p<0.001) activities than those incubated with ATP following pH 5.5 treatments. WST myofibrils had a lower (p<0.05) relative activity than RST following incubation at pH 5.5 without ATP. S1 ATPase activities decreased (p<0.05) with incubation pH in WST samples, but not in RST samples. WST S1 activity was higher (p<0.01) in samples exposed to pH 6 and 5.5 with actin bound compared to those incubated without actin. RST S1 exhibited a higher (p<0.01) relative activity than WST samples following pH 5.5 treatment with bound actin. These data show that low pH inactivates myofibrils by altering actin-activated S1 ATPase. Furthermore, these results suggest that muscles with high proportions of fast fibers are more susceptible to pH inactivation of ATPase activity and that the protective effect of actin binding to myosin is less in fast fibers. PMID- 22064236 TI - The relationship between muscle fiber characteristics, postmortem metabolic rate, and meat quality of pig longissimus dorsi muscle. AB - The aim of this study was to investigate the histochemical parameters of muscle fibers, and to estimate the correlation of muscle fiber characteristic to postmortem metabolic rate and meat quality traits in pigs. A total of 231 crossbred pigs were evaluated. Samples of the longissimus dorsi muscle were taken to evaluate the histochemical characteristics, postmortem metabolic rate and meat quality. Fiber type composition was mainly related to postmortem metabolic rate and meat quality traits among various muscle fiber characteristics. The percentage of type IIb fiber was negatively related to pH(45min) (r=-0.33) and positively to R-value (r=0.32). Drip loss was negatively related to fiber area percentages of type I and IIa (r=-0.25 and -0.26, respectively) and positively related to type IIb percentage (r=0.39). A similar tendency was found between lightness and fiber area percentage. In conclusion, increasing the percentage of type IIb fiber is related to increasing the postmortem metabolic rate, and is related to the deterioration of meat quality. PMID- 22064237 TI - Correlation of animal diet and fatty acid content in young goat meat by gas chromatography and chemometrics. AB - The meat fatty acids (FA) profiles of caprines submitted to different dietary treatments were determined by gas chromatography. The data were treated by Chemometrics to consider all variables together. The contents of saturated FA (SFA), monounsaturated FA (MUFA), polyunsaturated FA (PUFA), omega-3 (n-3) FA, and omega-6 (n-6) FA in 32 samples were analyzed. PUFA:SFA and n-6:n-3 ratios were also considered. The multivariate methods of hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to analyze the experimental results. HCA can group samples according to their basic composition, and PCA can explain the relationship among the dietary treatments according to the meat fatty acid composition. Treatment 1 presented the highest n-6 FA concentration, PUFA:SFA, and n-6:n-3 ratios, and the lowest MUFA and n-3 concentrations. Opposite results were observed for treatment 4. Treatments 2 and 3 were highly similar with differences mainly in SFA and MUFA concentrations. PMID- 22064238 TI - Heat and ultrafiltration extraction of broiler meat carnosine and its antioxidant activity. AB - This study examined the effects of extraction and further ultrafiltration on the carnosine content, antioxidant activity and total iron content of chicken muscle extracts. Fresh breast meat had 7-fold higher carnosine than fresh thigh meat (2900 versus 419MUg/g meat, respectively). Carnosine extracts of breast and thigh were prepared by heating at 60, 80 and 100 degrees C, and ultrafiltration (UF) using a 5000MW cut-off. At increasing temperatures, protein concentrations decreased while carnosine, total iron and antioxidant activity increased. Antioxidant abilities of the 80 and 100 degrees C-heated extracts were greater than that of the 60 degrees C extract (p<0.05). The ultrafiltrate from the 80 degrees C-heated extract had approximately 20% higher carnosine, but 40% lower protein and 10-30% lower iron than the 80 degrees C-heated ultrafiltrate. However, compared in terms of carnosine concentration, the meat extracts had greater antioxidant activity than pure carnosine (p<0.05). PMID- 22064239 TI - Effects of thawing temperature on the physicochemical properties of pre-rigor frozen chicken breast and leg muscles. AB - The objective of this study was to evaluate effects of thawing temperature on the biochemical and physicochemical properties of pre-rigor frozen chicken breast and leg muscles. Breast and leg muscles from 24 broiler chickens were excised within 10min postmortem. Pre-rigor muscles were frozen at -20 degrees C and thawed at 0 and 18 degrees C, and pH, R-value, sarcomere length, muscle shortening, thaw and cook loss, shear force and myofibrillar fragmentation index (MFI) compared with those in pre-rigor or 2 degrees C chilled muscles. The ultimate pH of 18 degrees C thawed muscle was lower than that of 0 degrees C thawed and 2 degrees C chilled muscles. As expected, the shortening of sarcomere length and muscle length of thaw rigor muscles were more than those of chilled muscle, but there were no significant differences between chilled muscle and 0 degrees C thawed muscle. Also, there were no significant differences in R-value (Abs 250/Abs 260) and cook loss due to thawing temperature. Samples thawed at 0 degrees C had higher MFI and lower shear value than samples thawed at 18 degrees C. Shear force value and MFI were not significantly different between chilled muscle and 0 degrees C thawed muscle. By thawing at 0 degrees C, thaw shortening was prevented, and tender meat comparable to the chilled meat was obtained. PMID- 22064240 TI - Carcass composition and meat quality differences between pasture-reared ewe and ram lambs. AB - Comparisons were made of carcass and meat quality characteristics of pasture raised Texel-cross ewe (n=269) and ram (n=275) lambs between 5 and 8 months of age with an average carcass weight of 17.2kg. Carcass assessment was based on linear dimensions and dissection of a leg into muscle, fat and bone, and meat quality measurements were made on M. semimembranosus and M. longissimus. At a set carcass weight, ewe lambs had higher dressing percentages (2%), shorter carcasses (0.7cm), and heavier leg cuts (35g) (P<0.01) than males. At the same leg weight, legs of ewe lambs were fatter than males (subcutaneous plus intermuscular fat; 11.2% vs 9.6%; P<0.001), whereas legs of ram lambs contained significantly more muscle and bone than females (P<0.001). Leg muscle to bone ratio (4.7 vs 4.4) and muscularity were higher for females than males (P<0.001). However, the relationship between leg muscle to bone ratio and muscularity was not the same between the sexes, and for any given muscularity value the muscle to bone ratio of ram lambs was lower than females. As a result, if carcass lean meat yield is predicted from a measure of carcass shape, such as muscularity, lean meat yields will be overestimated for males and underestimated for females. Meat quality was lower in ram lambs than in females (P<0.001) as shown by higher Warner-Bratzler shear values (peak value 109.8 vs 97.0N for M. Semimembranosus), higher ultimate meat pH values, and lower redness (a(*)) and lightness (L(*), for the longissimus muscle only) values (P<0.001). It is concluded that significant differences between ewe and ram lambs do exist for many carcass and meat quality traits, but for most quality traits the differences are small. PMID- 22064241 TI - Comparison of flavor changes in cooked-refrigerated beef, pork and chicken meat patties. AB - Beef and pork longissimus dorsi (LD) and semimembranosus (SM) and chicken breast (B) and thigh (T) muscles excised 24 h postmortem were ground by muscle/species group, formed into patties, pan-fried, refrigerated for 0, 3 or 6 days, and evaluated by a trained sensory panel for intensity of specific flavors. The rate of decline in species-specific natural meat flavor intensity and the rate of increase in "cardboard" (CBD) flavor intensity during the first half of the 6-day storage were fastest for beef, while such decline and increase during the entire storage period were slowest for chicken B. Overall trends of natural meat flavor and CBD intensity changes for chicken T appeared more like those for the red meats than chicken B. It was concluded that, while flavor deterioration can occur in cooked-stored meats from all the species, quantitative or the magnitude of differences between species would depend on muscle types and sensory terms/method used. PMID- 22064242 TI - Effects of chemical acidification and microbial fermentation on the rheological properties of meat products. AB - The gelation patterns of meat batters acidified with lactic acid bacteria (LAB) fermentation, liquid lactic acid, encapsulated lactic, citric and gluconic acids were studied. LAB provided slow (overnight) acidification that resulted in a significantly higher pre-cooking modulus of rigidity (G') value compared to all treatments, including a non-acidified control. The LAB heat-gelation pattern was also different from all other treatments. Liquid lactic acid caused an immediate pH reduction (from 5.6 to 4.6), crumbly texture, moisture release, and an initial higher G' value compared to the control, but lower than the LAB. The hydrogenated oil encapsulated acids, designed to release acid at 51-55 degrees C, did not produce crumbly texture or moisture release. Encapsulated lactic acid showed an increase in the initial G', probably because of limited pre-cooking acid release. However, citric and gluconic acids showed no such effect. During cooling, LAB treatment showed the lowest G' value curve, followed by the control, liquid lactic acid, and the encapsulated acids. PMID- 22064243 TI - Application of a multiplex PCR for the simultaneous detection of Escherichia coli O157:H7, Salmonella and Shigella in raw and ready-to-eat meat products. AB - Escherichia coli O157:H7, Salmonella and Shigella might contaminate similar types of meat products and cause deadly diseases in humans. Traditional microbiological analyses to detect these pathogens are labor-intensive and time-consuming. The objective of this study was to apply a multiplex PCR for simultaneous detection of the pathogenic bacteria in certain raw and ready-to-eat meat matrices. The tested samples had aerobic plate counts ranging from non-detectable, in chicken nuggets and salami, to 8.36log(10)CFU/g in ground pork. The pH of homogenates spanned from 6.86, in ground beef, to 7.17 in salami. Following a 24-h enrichment, the multiplex PCR assay could concurrently detect the three pathogens at 0.2log(10)CFU/g in ground beef, roast beef, beef frankfurters, chicken nuggets, salami and turkey ham, and 1.2log(10)CFU/g in ground pork. This multiplex PCR offers an efficient microbiological tool for presumptive detection of E. coli O157:H7, Salmonella and Shigella in meat. PMID- 22064244 TI - Exploring sub-lethal effects of exposure to a nucleopolyhedrovirus in the speckled wood (Pararge aegeria) butterfly. AB - This study investigated the sub-lethal effects of larval exposure to baculovirus on host life history and wing morphological traits using a model system, the speckled wood butterfly Pararge aegeria (L.) and the virus Autographa californica nucleopolyhedrovirus. Males and females showed similar responses to the viral infection. Infection significantly reduced larval growth rate, whilst an increase in development time allowed the critical mass for pupation to be attained. There was no direct effect of viral infection on the wing morphological traits examined. There was, however, an indirect effect of resisting infection; larvae that took longer to develop had reduced resource investment in adult flight muscle mass. PMID- 22064245 TI - Endoplasmic reticulum: ER stress regulates mitochondrial bioenergetics. AB - Endoplasmic reticulum (ER) stress activates an adaptive unfolded protein response (UPR) that facilitates cellular repair, however, under prolonged ER stress, the UPR can ultimately trigger apoptosis thereby terminating damaged cells. The molecular mechanisms responsible for execution of the cell death program are relatively well characterized, but the metabolic events taking place during the adaptive phase of ER stress remain largely undefined. Here we discuss emerging evidence regarding the metabolic changes that occur during the onset of ER stress and how ER influences mitochondrial function through mechanisms involving calcium transfer, thereby facilitating cellular adaptation. Finally, we highlight how dysregulation of ER-mitochondrial calcium homeostasis during prolonged ER stress is emerging as a novel mechanism implicated in the onset of metabolic disorders. PMID- 22064246 TI - Endoplasmic reticulum stress signaling is involved in silver nanoparticles induced apoptosis. AB - Although silver nanoparticles (AgNPs) have been reported to exert strong acute toxic effects on various cultured cells by inducing oxidative stress, the molecular mechanisms by which AgNPs-damaged cells are unknown. Because the endoplasmic reticulum (ER) may play an important role in the response to oxidative stress-induced damage and is quite sensitive to oxidative damage, we hypothesized that AgNPs may exert cytotoxic effects on cells by modulating ER stress. In our study, AgNPs resulted in cytotoxicity and apoptotic cell death when analyzing cell viability, DNA fragmentation and the apoptotic sub-G(1) population. Flow cytometry and confocal microscopy indicated that the cells were sensitive to AgNPs with respect to the induction of mitochondrial Ca(2+) overloading and enhancement of ER stress. AgNPs induced a number of signature ER stress markers, including phosphorylation of RNA-dependent protein kinase-like ER kinase (PERK) and its downstream eukaryotic initiation factor 2alpha, phosphorylation of inositol-requiring protein 1 (IRE1), splicing of ER stress specific X-box transcription factor-1, cleavage of activating transcription factor 6 (ATF6) and up-regulation of glucose-regulated protein-78 and CCAAT/enhancer-binding protein-homologous protein (CHOP/GADD153). Down-regulation of PERK, IRE1 and ATF6 expression using siRNA significantly decreased AgNPs induced the enhancement of ER stress. In addition, down-regulation of CHOP expression with siRNA CHOP attenuated AgNPs-induced apoptosis. Taken together, the present study supports an important role for the ER stress response in mediating AgNPs-induced apoptosis. PMID- 22064247 TI - Overexpression of polo-like kinase 1 and its clinical significance in human non small cell lung cancer. AB - Polo-like kinase 1 is a serine/threonine kinase which plays an essential role in mitosis and malignant transformation. The aim of this study was to investigate the prognostic significance of polo-like kinase 1 expression and determine its possibility as a therapeutic target in non-small cell lung cancer. Semi quantitative RT-PCR assay was performed to detect polo-like kinase 1 mRNA expression in non-small cell lung cancer cells or tissues. Immunohistochemistry was performed to detect polo-like kinase 1 protein expression in 100 non-small cell lung cancer tissue samples, and the associations of polo-like kinase 1 expression with clinicopathological factors or prognosis of non-small cell lung cancer patients were evaluated. RNA interference was employed to inhibit endogenous polo-like kinase 1 expression and analyzed the effects of polo-like kinase 1 inhibition on the malignant phenotypes of non-small cell lung cancer cells including growth, apoptosis, radio- or chemoresistance. Also, the possible molecular mechanisms were also investigated. The levels of polo-like kinase 1 mRNA expression in non-small cell lung cancer cell lines or tissues were significantly higher than those in normal human bronchial epithelial cell line or corresponding non-tumor tissues. High polo-like kinase 1 expression was significantly correlated with advanced clinical stage, higher tumor classification and lymph node metastasis of non-small cell lung cancer patients (P=0.001, 0.004 and 0.001, respectively). Meanwhile, high polo-like kinase 1 protein expression was also an independent prognostic molecular marker for non small cell lung cancer patients (hazard ratio: 2.113; 95% confidence interval: 1.326-3.557; P=0.017). Polo-like kinase 1 inhibition could significantly inhibit in vitro and in vivo proliferation, induce cell arrest of G(2)/M phase and apoptosis enhancement in non-small cell lung cancer cells, which might be activation of the p53 pathway and the Cdc25C/cdc2/cyclin B1 feedback loop. Further, inhibition of polo-like kinase 1 could enhance the sensitivity of non small cell lung cancer cells to taxanes or irradiation. Thus, polo-like kinase 1 might be a prognostic marker and a chemo- or radiotherapeutic target for non small cell lung cancer. PMID- 22064248 TI - Cooperativity between inhibition of cytosolic K+ efflux and AMPK activation during suppression of hypoxia-induced cellular apoptosis. AB - Cellular potassium homeostasis has recently emerged as a critical regulator of apoptosis in response to variety of stimuli. However, functional hierarchy of this phenomenon in the apoptotic cascade and therefore, its significance as a pathway for intervention is not fully established. Chronic hypoxia, a known threat to cell survival, also modulates cellular potassium homeostasis. In this study, we tested if hypoxia-induced apoptosis in lymphocytes can be prevented by modulating cellular K+ homeostasis. We observed that chronic hypoxia accelerated the rate of apoptosis in resting murine splenocytes concomitant with cytosolic K+ efflux. We tested several modalities including elevated extracellular potassium besides various K+ channel inhibitors to curtail hypoxia-induced K+ efflux and interestingly, established that the supplementation of KCl in extracellular medium was most effective in preventing hypoxia-induced apoptosis in these cells. Subsequent mechanistic dissection of pathways underlying this phenomenon revealed that besides effectively inhibiting hypoxia-induced efflux of K+ ion and its downstream cell-physiological consequences; elevated extracellular KCl modulated steady state levels of cellular ATP and culminated in stabilization of AMPKalpha with pro-survival consequences. Also, interestingly, global gene expression profiling revealed that KCl supplementation down regulated a distinct p53 regulated cellular sub-network of genes involved in regulation of DNA replication. Additionally, we present experimental evidence for the functional role of AMPK and p53 activation during suppression of hypoxia-induced apoptosis. In conclusion, our study highlights a novel bimodal effect wherein cooperativity between restoration of K+ homeostasis and a sustainable 'metabolic quiescence' induced by AMPK activation appeared indispensible for curtailing hypoxia-induced apoptosis. PMID- 22064249 TI - Diffuse large B-cell lymphoma as a sequela of Stevens-Johnson syndrome associated with an increased Epstein-Barr virus load. PMID- 22064250 TI - Progress in management of typhoid perforation. AB - Case fatality rate (CFR) for typhoid perforation (TP) has been on gradual but variable decline world wide. This review highlights the progress in management of TP from 1960 including the controversies, current principles of management and the advances associated with the best results of treatment. This is a review of publications on TP from 1960 to 2010 principally from Medline and Ovid databases. Main search terms used are typhoid and perforation. The median CFR by decade was estimated from studies that reported CFR. With advances in surgery and supportive care, median CFR for TP declined from over 50% in 1960 to single digits in the last decade in some countries but with West Africa lagging behind at 16%. Variations in CFR are attributed to differences in perforation-operation interval and quality of care. Opportunities now exist for patients with TP to recover from the disease but priority remains with prevention of enteric fever in endemic areas. PMID- 22064251 TI - Doppler ultrasound in the assessment of suspected intra-uterine growth restriction. AB - Small fetuses constitute a large heterogenous group that includes healthy small fetuses, chromosomally abnormal fetuses and fetuses suffering from utero placental insufficiency leading to restriction in fetal growth. This review outlines the diagnosis of intra-uterine growth restriction and describes how to differentiate this group from the group of healthy small fetuses. This is very crucial in the management of small fetuses in order to avoid unnecessary intervention in the healthy group, as well as avoid stillbirth and neonatal mortality and morbidity. PMID- 22064252 TI - Anemia in pregnancy at two levels of health care in Ibadan, south west Nigeria. AB - BACKGROUND: In Africa, anemia in pregnancy contributes to non-attainment of the MDG goals 4 and 5. This study examined the prevalence and some risk factors for anemia at two levels of health care in the Ibadan metropolis. METHODS: This was a retrospective study of the booking records of pregnant women at the University College Hospital (UCH, a profit-making tertiary institution) and Adeoyo Maternity Hospital (AMH, a secondary level institution offering free services) in Ibadan, September 1, 2008 to December 31, 2008. Eligible women had singleton pregnancies and no known chronic illnesses. Anemia was defined as packed cell volume (PCV) < 30%, and degrees of anemia as mild (PCV 27-29%), moderate (PCV 19-26%), and severe (PCV below 19%). Statistical analysis was done by the Chi-square test, Fisher exact test, and t-test. A P value of < 0.05 was considered significant. RESULTS: Data from 2702 women (384 and 2318 from UCH and AMH, respectively) were available for analysis. About 30% of the women were anemic. The patients in UCH had higher mean PCV (33.03 +/- 4.32 vs. 31. 04 +/- 4.09, P = 0.00). A higher proportion of anemia was seen in patients presenting in Adeoyo (32.4% vs. 16.7%, P = 0.00). Factors associated with anemia included young age (P = 0.00), low parity (P = 0.00), and hospital type (P = 0.00). Parity and hospital type remained significant on logistic regression. CONCLUSION: Lower prevalence of anemia at the tertiary hospital maybe attributed to the higher socioeconomic status of the clientele. Short-term early antenatal management of anemia and long term economic/educational empowerment is advocated. PMID- 22064253 TI - Profile and causes of mortality among elderly patients seen in a tertiary care hospital in Nigeria. AB - BACKGROUND: Old age is one of the factors associated with increased risk of dying when admitted to hospital. Therefore, aim of this study was to examine causes and pattern of death among elderly patients managed in a tertiary care hospital in Nigeria with scanty mortality records. MATERIALS AND METHODS: This prospective study was on deaths that occurred in patients 60 years and above admitted to University of Ilorin Teaching Hospital (UITH), Ilorin, between January 2005 and June 2007. Excluded were all brought-in-dead during the study period. Information obtained included demographic data, duration on admission, and diagnosis. Causes of death were determined from clinical progress notes and diagnosis. RESULTS: A total of 1298 deaths occurred during the study period, of which 297 occurred in persons 60 years and above with crude death rate of 22.8%. The mean age at death was 68 +/- 9 years (ranged 60-100 years). This consisted of 59% males and 41% females. Mean age at death for females was 69.7 +/- 8.7 years and for males 68.1 +/- 9.8 years (P = 0.05). Mean values of serum chemistry were sodium 137 +/- 8 mMol/l, potassium 3.6 +/- 1 mMol/l, urea 11 +/- 8 mMol/l, and creatinine 126 +/- 91 MUmol/l. The value of mean haemogram concentration was 10.5 +/- 3 gm/dl and white cell count was 12 +/- 2 * 10(9)/mm3. The three most common diagnoses at deaths were stroke (19.8%), sepsis (16.5%), and lower respiratory tract disease (8.1%). Infectious diseases accounted for 38.2% of all diagnoses. Collective mean length of hospital stay (LOS) at death was 6.8 +/- 8.6 (ranged 15 minutes-60 days). Close to 27.4% of the deaths occurred within 24 hours and neurological disorder had shortest hospital stay (4.6 +/- 6.3 days), followed by endocrine disorders (6.8 +/- 8.4 days) and respiratory diseases (8.4 +/- 5.6 days) [P = 0.001]. CONCLUSION: Hospital mortality is high amongst older people. Stroke and infectious diseases are leading causes of death. Efforts should be geared toward reducing risk for cardiovascular diseases and improvement on level of personal and community hygiene. PMID- 22064254 TI - Dyslipidemias in type 2 diabetes mellitus patients in Nnewi South-East Nigeria. AB - BACKGROUND: Dyslipidemia has been noted to play an integral role in the pathogenesis and progression of micro and macrovascular complications in diabetes mellitus patients. The complications exemplified by renal vascular and cardiovascular disease cause the most morbidity and mortality in this group of patients. OBJECTIVE: This study is aimed at understanding the pattern of dyslipidemia among type 2 diabetic patients. MATERIALS AND METHODS: A total of 108 consenting adult type 2 diabetic patients seen in the medical unit of the Nnamdi Azikiwe University Teaching Hospital Nnewi were evaluated in this crosssectional study. Their fasting lipid profile, fasting blood glucose, weight, height and blood pressure were evaluated. RESULT: The prevalence of dyslipidemia (at least one abnormal lipid profile) was 90.7%. The 24.1% had single dyslipidemia while 66.6% had combined dyslipidemia. Reduced HDL constituted the highest single abnormality (62%) followed by hypertriglyceridemia (56.5%), hypercholesterolemia (53.7%) and high LDL in (44.4%). The duration of DM was not significantly associated with dyslipidemia (P > 0.05). CONCLUSION: Dyslipidemia is highly prevalent among type 2 diabetic patients in Nigeria with the majority of the patients having combined dyslipidemia. We recommend that aggressive treatment of lipidemia and hyperglycemia can be instituted to reduce the risk of macro and microvascular complications. PMID- 22064255 TI - Should non acute and recurrent headaches have neuroimaging before review by a Neurologist?--a review in a Southern Nigerian Tertiary Hospital. AB - BACKGROUND: Headache is a common complaint in general practice and it is known that most headaches are primary and that the yield of neuroimaging like cranial computed tomography (CT) in headache is generally low. In this study, we were able to demonstrate that the yield of neuroimaging in non-acute and recurrent headache could be higher if cases are reviewed first by a specialist Neurologist before cranial CT. METHOD: Seventy-four cases that were referred to the specialist neurology clinic with complaints of chronic and recurrent headaches without focal neurological deficit that had CT scan were reviewed consecutively using the short form of the International Classification of Headache Disorders second edition (ICHD 2) criteria after their demographics of age, sex were captured, to find out the proportion and characteristics of study cases that had identifiable cranial lesions on cranial CT scan. All cases were reviewed by a specialist Neurologist before CT scan and all CT films were reviewed by a specialist Radiologist. Age, sex and the distribution of CT findings were described from a frequency table and mean age of study cases with and without identifiable lesions on CT were compared with t-test for any significant difference and the effect of gender on the presence of identifiable lesions was tested with chi square and the agreement between clinical and CT diagnoses were tested on kappa statistics. RESULTS: (1) Mean age of cases was 37.55 (22.06) years. (2) No significant effect of gender was found on intracranial lesions (P = 0.345). (3) Intracranial lesions were found in 47.3% of cases and the mean age was higher compared to cases with normal findings on cranial CT (P = 0.019). (4) Clinical and CT diagnoses agreed in 56.2% of the cases (P = 0.000). CONCLUSION: The high yield of intracranial lesions may be accounted for by the method of selection of cases for cranial CT. PMID- 22064256 TI - Awareness and utilization of protective eye device among welders in a southwestern Nigeria community. AB - OBJECTIVE: To determine the level of awareness and practice of use of protective eye devices among welders in Ile-Ife. METHODS: This is a cross-sectional descriptive study of 405 consenting welders. A pretested proforma was utilized to obtain information on sociodemographic characteristics, as well as awareness and use of protective eye device. RESULTS: The age of the respondents ranged from 16 to 80 years. The mean age was 39 +/- 13 years. A large proportion (315, 78%) of the welders was aged between 21 and 50 years. The youngest group aged <= 20 years accounted for 15 (4%) of all welders, while the oldest group aged > 60 years accounted for 21 (5.2%). 402 were males (99.3%) and three were females (0.7%). Three hundred thirty-six (83%) of the welders had practiced for 6 years and above. There was a high level of awareness of protective eye devices among the welders (367, 90.6%), being higher among arc welders compared with gas welders (P < 0.001). Less than half (186, 45.9%) of the welders possessed protective eye devices. Of these, only 39 (9.6%) made use of the devices always. Some of the reasons for not using the protective eye devices include discomfort and poor visibility (56, 13.6%) and inadequate appreciation of the necessity to wear it (49, 12.1%). CONCLUSION: The findings of this study suggest that a significant proportion of welders in Ile-Ife were not utilizing protective eye device. Health education and awareness campaigns about the importance and benefits of utilizing protective eye devices are recommended. PMID- 22064257 TI - Features and perceptions of menopausal women in Benin City, Nigeria. AB - BACKGROUND/OBJECTIVE: The features of menopause have always been assumed to occur only to a minor degree of significance in Nigerian women. Perceptions of menopausal symptoms are greatly influenced by social, cultural and economic settings and may influence the mode of treatment for menopausal symptoms. The aim of this study was to determine the features and perceptions of natural menopause among menopausal women in Benin-City, Edo State, Nigeria. METHODS: A descriptive cross-sectional study of 533 randomly selected Nigerian women in Benin City, Edo State who had experienced at least 24 continuous months of amenorrhea using a structured questionnaire. RESULTS: The ages of the women studied ranged between 47 and 78 years; mean 57.4 +/- 6.3 years. The mean menopausal and menercheal ages were 49.8 +/- 2.6 and 15.2 +/- 2.0 years. Most (80.7%) were currently married with 63.6% in monogamous relationships. Three hundred and fifty-six women (66.8%) have heard of the word menopause and correctly described it. Menopause was considered a normal event by 97.4%. Majority (407; 77.6%) adjusted very well to the events of menopause with none revealing any serious maladjustment. Three hundred and forty-six women (64.9%) were no longer sexually active. Joint pains (287; 53.8%), hot flushes (272; 51%) and night sweats (22; 42%) were the most common symptoms believed to be related to menopause. Three hundred and two women (56.7%) actually suffered at least one of the menopause symptoms. Joint pains (52.9%), hot flushes (43.3%) and night sweats (29.8%) were the commonest symptoms experienced. Freedom from monthly bleeding (50.7%) was the most commonly reported advantage of menopause. Only thirty nine (7.3%) were aware of hormone replacement therapy (HRT) and none were on /ever had HRT. CONCLUSION: Although menopause is well-tolerated by women in our environment, it needs further investigation. Research priorities include the influence of socio-cultural beliefs on sexuality at menopause and evaluation of HRT benefits. PMID- 22064258 TI - Maternal and fetal outcome in patients with eclampsia at Murtala Muhammad specialist Hospital Kano, Nigeria. AB - BACKGROUND/OBJECTIVES: Eclampsia is a major contributor to maternal and perinatal mortality worldwide. It is much more common in developing countries like Nigeria where presentation is usually late and resources are scarce. The staggering figures of maternal death (46%) reported by the Society of Obstetricians and Gynaecologists of Nigeria (SOGON) in 2004 moved the Kano State government to initiate programs that will reduce maternal mortality in the state. The objectives of this report were; 1) to determine the prevalence of eclampsia at Murtala Muhammad Specialist hospital (MMSH) Kano between April 2008 and May 2009; 2) to determine maternal and fetal outcome in eclamptic patients admitted to MMSH Kano between April 2008 and May 2009. METHODS: Case records of all patients admitted to MMSH between April 2008 and May 2009 were retrieved and analyzed using Epi-info version 3.2.2 April 2004 (CDC Atlanta, USA). Information extracted includes demographic data, maternal and fetal outcome. A P value of less than 0.05 was considered significant. RESULTS: There were 688 eclamptic patients admitted and 13 943 women delivered during the study period giving a prevalence of 5% of total deliveries. One hundred and twenty six women died giving a maternal mortality ratio (MMR) of 904/100 000, among them 36 were eclamptics. The perinatal mortality rate for the eclamptics was 132/1 000. 81.4% of the women were primigravidas and majority (82.2%) were at term. Almost 83.3% presented within 12 hours of the onset of the fits and nearly half (44.9%) had their convulsion before the onset of labor. CONCLUSION: The incidence of eclampsia is 5% of total deliveries. Delay in presentation is associated with poor outcome. PMID- 22064259 TI - Disseminated Langerhan's cell histiocytosis: a case report and review of the literature. AB - Langerhan's cell histiocytosis is characterized by the presence of large mononucleated cells associated with inflammatory cells. We describe the clinical presentation, histopathology and some immunohistochemistry findings, in an eight year-old female patient. PMID- 22064260 TI - Prognosis of idiopathic intracranial hypertension in Saudi Arabia. PMID- 22064261 TI - Referral for assisted reproductive technology: indications and treatment outcome. PMID- 22064262 TI - The influence of passive wrist joints on the functionality of prosthetic hands. AB - BACKGROUND: The addition of a passive wrist to a single degree of freedom prosthesis has an effect on its functionality. The amount of impact is undetermined. OBJECTIVES: To measure the grasping function of a commercial single degree of freedom hands with and without two forms of passive wrist flexor. STUDY DESIGN: Form-board and timed tasks. METHOD: Repeated measures with a single subject using a validated assessment tool. The test measured the function of one conventional, single axis, powered hand controlled by the same myocontroller format. It was used in conjunction with a passive three position wrist flexor, a wrist with compliance in the flex/extend and radial/ulnar deviation and compared with a hand without these axes. RESULTS: The overall functional score of the hand alone was 80 out of 100. The use of a wrist flexion unit resulted in a higher score (83) and the compliant wrist achieved a score of 79. The addition of a wrist allowed improved performance in Power, Lateral and Tips grips for both wrist designs, in addition the Extension grip was improved with the compliant wrist. CONCLUSION: Wrist flexion had a positive impact on the functional score. It enabled some tasks to be performed quicker and with less difficulty. PMID- 22064263 TI - Pf332-C231-reactive antibodies affect growth and development of intra erythrocytic Plasmodium falciparum parasites. AB - The Plasmodium falciparum antigen 332 (Pf332), is a megadalton parasite protein expressed at the surface of infected red cells during later stages of the parasite's developmental cycle. Antibodies to different parts of this antigen have been shown to inhibit parasite growth and adherence to host cells with or without ancillary cells. However, the mechanisms involved in these inhibitions remain largely unknown. We further analysed the activities of specific antibodies with regard to their specific mechanisms of action. For these analyses, affinity purified human antibodies against epitopes in the C-terminal fragment of Pf332 (Pf332-C231) were employed. All purified antibodies recognized Pf332-C231 both by immunofluorescence and ELISA. IgG was the main antibody isotype detected, although all sera investigated had varying proportions of IgG and IgM content. All the antibodies showed a capacity to inhibit parasite growth in P. falciparum cultures to different extents, mainly by acting on the more mature parasite stages. Morphological analysis revealed the antibody effects to be characterized by the presence of a high proportion of abnormal schizonts (15-30%) and pyknotic parasites. There was also an apparent antibody effect on the red cell integrity, as many developing parasites (up to 10% of trophozoites and schizonts) were extracellular. In some cases, the infected red cells appeared to be disintegrating/fading, staining paler than surrounding infected and uninfected cells. Antigen reversal of inhibition confirmed that these inhibitions were antigen specific. Furthermore, the growth of parasites after 22-42h exposure to antibodies was investigated. Following the removal of antibody pressure, a decreased growth rate of these parasites was seen compared to that of control parasites. The present study confirms the potential of Pf332 as a target antigen for parasite neutralizing antibodies, and further indicates that epitopes within the C231 region of Pf332 should constitute important tools in the dissection of the role of Pf332 in the biology of the malaria parasite, as well as in the design of a malaria vaccine. PMID- 22064264 TI - HIV-1 and influenza antigens synthetically linked to IgG2a Fc elicit superior humoral responses compared to unmodified antigens in mice. AB - Using murine IgG subclass molecules (IgG1 or IgG2a) synthetically fused to HIV-1 or influenza test antigens, we explored the potential for IgG Fc scaffolds to augment immunogenicity. Each antigen (Ag) was grafted onto a hinge-Fc scaffold containing all critical residues necessary for interaction with effector cells, thus retaining effector functions of the native IgG subclass. We hypothesized that the differential affinity of FcgammaRs for specific IgG subclasses would influence the magnitude of immune responses elicited by immunization with an Ag IgG Fc fusion vaccine. We demonstrate here that the antigen-specific humoral response elicited by Ag-IgG2a fusion vaccines is at least tenfold greater than that elicited by native antigen, that this response is superior to that elicited by Ag-IgG1, and that the augmented antigen-specific humoral response elicited is Fcgamma receptor-dependent. PMID- 22064265 TI - Enhanced memory B-cell immune responses after a second acellular pertussis booster vaccination in children 9 years of age. AB - Whooping cough has made its comeback and the incidence of pertussis in countries with widespread pertussis vaccination is most prominent in individuals above 9 years of age. To control the burden of infection, several countries already introduced acellular pertussis (aP) booster vaccination in adolescents and/or adults. However, antibody levels wane rapidly after vaccination even at older age. In this longitudinal study we investigated the effect of a second aP booster on the pertussis-specific memory B-cell immunity in children 9 years of age that have previously been vaccinated according to the national immunization program. Longitudinal blood samples were taken before, one month and one year after the booster. Purified B-cells were polyclonally stimulated and frequencies of memory B-cells were identified by ELISPOT-assays specific for various pertussis antigens. In addition, IgG levels and avidity indices were measured with fluorescent bead-based multiplex immunoassays. Starting with low pertussis specific antibody and memory B-cell levels, a typical booster response was measured at one month after vaccination with increased antibody and memory B-cell responses. Although these responses declined slightly after one year, they substantially exceeded pre-booster levels and the avidity indices of the anti pertussis antibodies remained high. Furthermore, high numbers of pertussis specific memory B-cells at one-month post-booster correlate quite reliably with the corresponding high antibody response at one-year follow-up. In conclusion, booster vaccination in children 9 years of age induced an enhanced pertussis specific memory immune response that sustained at least for one year. Therefore, this study supports the introduction of booster vaccination in older age groups. PMID- 22064266 TI - Innocuousness and safety of classical swine fever marker vaccine candidate CP7_E2alf in non-target and target species. AB - Chimeric pestivirus CP7_E2alf is a promising live marker vaccine candidate against classical swine fever. Prior to a possible application in the field, several safety aspects have to be addressed. Due to the fact that CP7_E2alf is based on a bovine viral diarrhea virus backbone, its behavior in ruminants is of particular interest. In the framework of this study, its innocuousness in non target species was addressed by inoculation of calves, young goats, lambs, and rabbits. To this means, high titres of CP7_E2alf were applied orally to three animals of each species. Additional animals were left as unvaccinated contact controls. During the study, all animals remained clinically healthy, and neither fever nor leukopenia were observed. Virus could not be isolated from purified white blood cells or from nasal or faecal excretions. Moreover, none of the animals (inoculated or contact control) seroconverted. In the target species, innocuousness, shedding and transmission of vaccine virus was addressed in different animal trials that were carried out primarily for the purpose of efficacy, potency or duration of immunity studies. In all experiments, CP7_E2alf proved to be completely safe for the vaccinees and unvaccinated contact controls. Furthermore, no shedding or transmission was detected in any of the experiments. Even after parental vaccination, vaccine virus genome was barely detectable in blood or organ samples of vaccinated animals. Thus, CP7_E2alf can be regarded as completely safe for both target and non-target species. PMID- 22064267 TI - An open-label, randomized, multi-center study of the immunogenicity and safety of DTaP-IPV (KinrixTM) co-administered with MMR vaccine with or without varicella vaccine in healthy pre-school age children. AB - BACKGROUND: In the US, it is recommended that 4-6 year old children receive diphtheria-tetanus-acellular pertussis (DTaP), inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella (V), and influenza vaccines. Data relating to the concomitant administration of combination DTaP-IPV vaccine (KinrixTM; GlaxoSmithKline Biologicals) and influenza or V vaccines are currently limited. This study was undertaken to evaluate the immunogenicity and reactogenicity of KinrixTM when co-administered with MMR (M-M-RII((r)), Merck & Co.) and VarivaxTM (Merck & Co.) in 4-6 year old children. METHODS: Phase IIIb, open-label, non inferiority study (NCT00871117). We randomized (1:1) healthy 4-6 year olds to receive KinrixTM+MMR+V on day 0 (Group 1), or KinrixTM+MMR on day 0, followed by V at month 1 (Group 2). We measured DTaP-IPV immunogenicity before and 1 month post-vaccination (prior to V vaccination in Group 2). We collected local and general solicited symptoms within 4 days after vaccination and serious adverse events (SAEs) through 6 months post-vaccination. RESULTS: We enrolled 478 subjects. One month post-vaccination, >95% of subjects in both groups had booster responses to diphtheria, tetanus and pertussis antigens and all subjects had seroprotective anti-poliovirus antibody titers. Immune responses in Group 1 were non-inferior to Group 2 for responses to DTaP-IPV antigens according to pre specified criteria. Reporting of solicited local events at the DTaP-IPV site appeared to be similar between the two vaccine groups, as was reporting of solicited general adverse events within 4 days of vaccination; no vaccine related SAEs were reported. CONCLUSION: Concomitant administration of varicella vaccine with KinrixTM and MMR did not impact the immunogenicity of diphtheria, tetanus, pertussis or poliovirus antigens. Both vaccine regimens were well tolerated. These results support the co-administration of DTaP-IPV, MMR, and V vaccines in 4 6-year-old children, providing protection against multiple diseases in a timely and efficient manner. PMID- 22064268 TI - Antibody response to the influenza vaccine in healthcare workers. AB - People vaccinated against influenza develop hemagglutination inhibition (HAI) antibodies (Ab) that bind to the virus and neutralize it. Ab titer levels are variable depending on factors insufficiently studied, and tend to decrease over time. In the present study, we analyzed antibodies responses before and after influenza vaccination in nurses working in a hospital, with the aim of: - identifying seroconversion rates to trivalent influenza vaccine one month after immunization; - evaluating if, six months after vaccination, influenza HAI Ab titer fall comparing to one-month post vaccination HAI Ab titer; - studying the association between the lack of HAI Ab response (seroconversion) assessed one month after immunization and: ? past influenza vaccinations, ? baseline (before vaccination) HAI Ab titer, ? baseline (before vaccination) HAI Ab titer >= 40 (considered as a protection titer). Hemagglutination inhibition reaction was used to assess specific HAI Ab titers against influenza A(H(1)N(1)), A(H(3)N(2)) and B virus strains included in the influenza vaccine and we used progressive dilutions of two times, starting on 1:10 until 1:20.480. Seroconversion rates, one month after vaccination, were 66.7% for A(H(1)N(1)) strain, 63.2% for A(H(3)N(2)) strain and 56.3% for B strain. The most immunogenic strain used in 2007/08 influenza vaccine was A(H(1)N(1)). Seroconversion rates after one month were negatively associated with past influenza vaccinations, baseline HAI Ab titers >= 40 and baseline HAI Ab titers. Six months after vaccination, 50% of participants showed a drop in HAI Ab titers to an half, for each of the considered strains, but they remain high enough to protect against the disease. PMID- 22064269 TI - MAOS and medicinal chemistry: some important examples from the last years. AB - This review aims to highlight microwave-assisted organic synthesis as applied to medicinal chemistry in the last years, showing some reactions performed under microwave irradiation for the synthesis of distinct structurally molecules of biological interest, divided into the following groups: antineoplastics, anti inflammatory, antimicrobial agents, antivirals, agents for the treatment of neglected diseases and central nervous system-acting prototypes. PMID- 22064270 TI - Effect of the lectin of Bauhinia variegata and its recombinant isoform on surgically induced skin wounds in a murine model. AB - Lectins are a structurally heterogeneous group of highly specific carbohydrate binding proteins. Due to their great biotechnological potential, lectins are widely used in biomedical research. The purpose of the present study was to evaluate the healing potential of the lectin of Bauhinia variegata (nBVL) and its recombinant isoform (rBVL-1). Following surgical creation of dorsal skin wounds, seven groups of mice were submitted to topical treatment for 12 days with lectin, D-galactose, BSA and saline. The animals were anesthetized and euthanized on POD 2, 7 and 12 in order to evaluate the healing potential of each treatment. The parameters considered included wound size, contraction rate, epithelialization rate and histopathological findings. Wound closure was fastest in animals treated with rBVL-1 (POD 7). nBVL was more effective than the controls. All skin layers were reconstructed and keratin deposition increased. Our findings indicate that the lectin of Bauhinia variegata possesses pro-healing properties and may be employed in the treatment of acute skin wounds. PMID- 22064271 TI - Synthesis, characterization, acetylcholinesterase inhibition, molecular modeling and antioxidant activities of some novel Schiff bases derived from 1-(2 ketoiminoethyl)piperazines. AB - Some novel Schiff bases derived from 1-(2-ketoiminoethyl)piperazines were synthesized and characterized by mass spectroscopy, FTIR, UV-Visible, 1H and 13C NMR. The compounds were tested for inhibitory activities on human acetylcholinesterase (hAChE), antioxidant activities, acute oral toxicity and further studied by molecular modeling techniques. The study identified the compound (DHP) to have the highest activity among the series in hAChE inhibition and DPPH assay while the compound LP revealed the highest activity in the FRAP assay. The hAChE inhibitory activity of DHP is comparable with that of propidium, a known AChE inhibitor. This high activity of DHP was checked by molecular modeling which showed that DHP could not be considered as a bivalent ligand due to its incapability to occupy the esteratic site (ES) region of the 3D crystal structure of hAChE. The antioxidant study unveiled varying results in 1,1 diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. This indicates mechanistic variations of the compounds in the two assays. The potential therapeutic applications and safety of these compounds were suggested for use as human acetylcholinesterase inhibitors and antioxidants. PMID- 22064272 TI - Chemical constituents and biological studies of the leaves of Grevillea robusta. AB - Three new compounds: Graviquinone (1), cis-3-hydroxy-5-pentadecylcyclohexanone (2), and methyl 5-ethoxy-2-hydroxycinnamate (3), and thirty-eight known compounds were isolated and identified from the leaves of Grevillea robusta. The structures of these compounds were determined by spectroscopic and chemical transformation methods. Graviquinone (1) showed the strongest cytotoxicity against MCF-7, NCI H460, and SF-268 cell lines. Methyl 2,5-dihydroxycinnamate (4), graviphane (13), and dehydrograviphane (14) exhibited very potent DPPH scavenging activity compared with alpha-tocopherol. Methyl 2,5-dihydroxycinnamate (4) and bis norstriatol (17) demonstrated strong inhibition of L-DOPA oxidation by mushroom tyrosinase compared with kojic acid. PMID- 22064273 TI - Consecutive three-component synthesis of 3-(hetero)aryl-1H-pyrazoles with propynal diethylacetal as a three-carbon building block. AB - A novel consecutive three-component synthesis of 3-(hetero)aryl-1H-pyrazoles via room temperature Sonogashira arylation of propynal diethylacetal used as a propargyl aldehyde synthetic equivalent has been disclosed. The final acetal cleavage-cyclocondensation with hydrazine hydrochloride at 80 degrees C rapidly furnishes the title compounds in a one-pot fashion. PMID- 22064274 TI - Triprolidinium dipicrate. AB - In the tripodinium cation of the title compound {systematic name: 2-[(E)-1-(4 methyl-phen-yl)-3-(pyrrolidin-1-ium-1-yl)prop-1-en-yl]pyridinium bis-(2,4,6 trinitro-phenolate)}, C(19)H(24)N(2) (+).2C(6)H(2)N(3)O(7) (-), the N atoms on both the pyrrolidine and pyridinium groups are protonated. The pyrrolidine group adopts a slightly distorted envelope configuration. Strong N-H?O cation-anion hydrogen bonds and weak inter-molecular N-H?O inter-actions link the dication and two anions. In both picrate anions, the nitro groups display rotational disorder over two orientations in a 0.605 (6):0.395 (6) ratio. The crystal packing also features weak inter-molecular pi-pi [centroid-centroid distance = 3.8036 (14) A] and C-H?O inter-actions. PMID- 22064275 TI - O,O'-2-Iodo-1,3-phenyl-ene bis-(diphenyl-phosphinothio-ate). AB - The title compound, C(30)H(23)IO(2)P(2)S(2), was synthesized by the reaction of 2 iodo-benzene-1,3-diol, chloro-diphenyl-phosphine, Et(3)N and sulfur. The P=S bonds project to opposite sides of the central aromatic ring. The O-P-S and C-P-S bond angles are significantly larger than the O-P-C and C-P-C bond angles, indicating significant distortion of the tetra-hedral geometries of the P atoms. The P=S bond lengths of 1.9311 (13) and 1.9302 (12) A in the title compound are shorter than that found in Ph(3)P=S [1.950 (3) A] because the replacement of one C atom attached the P atom by an O atom increases the effective electronegativity of the P atom. PMID- 22064276 TI - 10-Hy-droxy-benzo[h]quinolinium tetra-chlorido(2-methyl-quinolin-8-olato kappaN,O)stannate(IV) methanol disolvate. AB - In the disolvated title salt, (C(13)H(10)NO)[SnCl(4)(C(10)H(8)NO)].2CH(3)OH, the Sn(IV) atom is chelated by the N,O-bidentate 2-methyl-quinolin-8-olate ion and is further coordinated by four chloride ions, showing a distorted octa-hedral SnNOCl(4) geometry. In the crystal, the cation and anion are linked to the methanol mol-ecules by O-H?O and N-H?O hydrogen bonds. PMID- 22064277 TI - Comparison of glucose, glucose 6-phosphate, ribose, and mannose as flavour precursors in pork; the effect of monosaccharide addition on flavour generation. AB - The effect of glucose, glucose 6-phosphate, mannose and ribose on the generation of aroma volatiles in pork was investigated. The monosaccharides were added individually to minced pork prior to heat treatment (160 degrees C for 10min) in the following concentrations: glucose (27.5MUmol/g), ribose (1.2MUmol/g), mannose (8.3MUmol/g) and glucose 6-phosphate (0.5MUmol/g). The natural concentrations of the monosaccharides in the pork used were found to be 4.0MUmol/g for glucose, 0.1MUmol/g for ribose, 0.3MUmol/g for mannose and 2.6MUmol/g for glucose 6 phosphate. The major aroma compounds identified in the headspace of the heated samples were pyrazines, aldehydes (Strecker and lipid-derived), ketones, and sulphides. Glucose generated the highest amounts of volatiles followed by glucose 6-phosphate. However, when related to the added concentration of glucose 6 phosphate, this phosphorylated monosaccharide showed the highest aroma generating potential. The addition of ribose did not increase the concentration of volatiles compared with pork without the added monosaccharide. The fates of ribose 5 phosphate and ribose in pork were studied over time. The concentrations of ribose and ribose 5-phosphate clearly decreased during 2h equilibration, which may be due to enzymatic activities. These precursors may, therefore, be less important pork flavour precursors than glucose and glucose 6-phosphate. PMID- 22064278 TI - Dynamic viscoelastic characterisation of ostrich-meat yor (Thai sausage) following pressure, temperature and holding time regimes. AB - Ostrich-meat yor (Thai sausage) was pressurized at 200, 400 and 600MPa, with 40 and 50 degrees C for 40 or 60min, subsequently, the products were assessed by stress control rheometry. Two types of viscoelastic measurement were made. The first was an oscillatory analysis performed at a frequency range of 0.01-10Hz using a stress of 30Pa. Secondly, creep and recovery testing was performed with an initial load of 30Pa for 300s, unloaded recovery 900s. Finally, the products were subjected to sensory evaluation using a 9-point hedonic scale. To support the rheological measurement, SDS-PAGE electrophoretic analysis was also applied. The viscoelastic characterisation of all treated ostrich-meat yor showed that G' was larger than G" with small tan delta values (0.23) and the difference between G' and G" of each plot was relatively one log cycle. These indicated solid-like behaviour with the predominance of an elastic component. Whereas all creep curves of the treated samples were best characterised by a four-element "Burgers" model in which the J(0) data and retardation time (lambda(ret)) suggested that increasing pressure levels, temperature and holding time significantly affected the viscoelastic properties of the samples. The electrophoregrams indicated that these structural changes which might be associated with the formation of hydrophobic interactions and disulphide bonding. Most sensory attributes of the pressure treated products received higher scores than conventionally steamed products. PMID- 22064279 TI - Relationship of temperament, growth, carcass characteristics and tenderness in beef steers. AB - Relationships of temperament evaluated at different production stages with growth, carcass characteristics and beef tenderness were determined in Bonsmara crossbred steers managed under commercial managent. Temperament was evaluated at weaning and at initiation of the finishing phase. Steers from a Roswell, NM ranch (n=156) and a Cline, TX ranch (n=21) were stratified at fall weaning by weight and source and randomly allotted to winter ryegrass at Uvalde or Overton, TX followed by feeding in a commercial feedlot near Batesville, TX. Cattle were observed for temperament (escape velocity, EV, m/s; pen and chute temperament score, PTS and CTS) at weaning and upon entry to the feedlot. Cattle were harvested at approximately 7 mm 12th rib fat. Carcass data was taken approximately 36 hrs post-mortem and 2.5cm thick steaks were removed from the 13th rib for Warner-Bratzler shear force (WBS) determination. The only measures of temperament significantly related to performance were EV and PTS. Weaning EV appeared to be more related to feedlot ADG (r=-0.26, P<0.003), ribeye area (r= 0.37, P<0.0008), yield grade (r=0.29, P<0.01) and WBS, r=0.27, P<0.005) than did the later measures of temperament. However, in-feedlot EV was associated with feedlot weights (r=-0.28, P<0.0004). Results of this research suggest temperament, particularly at weaning, is related to feedlot performance, carcass merit, and beef tenderness at a low to moderate level and evaluation of this trait may be a helpful management tool. PMID- 22064280 TI - Predicting Longissimusdorsi myoglobin oxidation in aged beef based on early post mortem colour measurements on the carcass as a colour stability index. AB - Sixty young bulls of the Pirenaica breed, representative of the beef production and marketing system in northern Spain, were used. The carcass grading and weight, pH at 24h post-mortem, and objective colour measurements (CIE L(*)a(*)b(*)) were recorded on the Latissimus dorsi, Rectus abdominis and Longissimus dorsi in order to find indicators and predictors of beef colour stability (Longissimus dorsi metmyoglobin percentage on ageing for 3, 7 and 14days) by means of early post-mortem measurements on the carcass. Neither the conformation nor the degree of fattening, under the current EU beef carcass classification system, displayed any statistically significant relationship with colour stability of beef aged 3, 7 and 14days. However, there was a relationship between the instrumental colour measured on the carcass and the colour stability of the beef. This relationship allowed prediction of colour stability (Longissimus dorsi MMb percentage) after 3, 7 and 14days of ageing and 48h blooming using colour coordinates measured on the carcass. PMID- 22064281 TI - Liberation of actin from actomyosin in meats heated to 65 degrees C. AB - This study investigated whether actin liberation from myofibrils occurs during the heating of various muscles, as well as squid mantle muscle at temperatures, such as 60 degrees C, employed for vacuum cooking of meats. Actin liberation was demonstrated in scallop striated adductor muscle, but not in beef, pork, or chicken, using the detection method previously employed with squid muscle, in which liberated actin was detected with SDS-PAGE, in the supernatant obtained by centrifugation of the homogenate of heated muscle in 0.2M KCl at a neutral pH. However, actin liberation was demonstrated in beef, pork and chicken by a new detection method, in which heated muscle was homogenized in 0.6M KCl or NaCl at a slightly alkaline pH and maintained at 4 degrees C for 16h with stirring, after which the homogenate was diluted three times with water and centrifuged to obtain the supernatant containing the liberated actin. This new method indicated that actin liberation in beef, pork, and chicken was marked by heating at 65 degrees C, but scarcely induced at 80 degrees C. Thus, the liberation of actin from myofibrils may contribute to the greater tenderness of vacuum-cooked meat (meat heated at a low temperature for long time), as compared with meat prepared by cooking at a higher temperature. PMID- 22064282 TI - Irradiated Chinese Rugao ham: Changes in volatile N-nitrosamine, biogenic amine and residual nitrite during ripening and post-ripening. AB - N-nitrosamines, biogenic amines and residual nitrite are harmful substances and often present in cured meat. The effects of gamma-irradiation (gamma-irradiation) on these chemicals in dry-cured Chinese Rugao ham during ripening and post ripening were investigated. Rugao hams were irradiated at a dose of 5kGy before ripening and were then ripened in an aging loft. Although gamma-irradiation degraded tyramine, putrescine and spermine, on the other hand, it promoted the formation of spermidine, phenylethylamine, cadaverine and tryptamine. Residual nitrite was significantly reduced by gamma-irradiation. N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA) and N-nitrosopyrrolidine (NPYR) were found in Chinese Rugao ham during ripening and post-ripening but could be degraded with gamma-irradiation. The results suggest that gamma-irradiation may be a potential decontamination measure for certain chemical compounds found in dry-cured meat. PMID- 22064283 TI - A novel fiber optic sensor to monitor beef meat emulsion stability using visible light scattering. AB - Accurate control of the meat emulsification process for a consistent product quality entails the development of an on-line optical sensor technology to determine the optimum chopping end-point yielding minimum cooking loss and a fine texture. Previous studies suggested that light backscatter measurements can be used to monitor physical-chemical changes during emulsification in comminuted meat products if appropriate spacing between the emitting and detecting optical fibers is used. Light backscatter intensity from beef emulsions manufactured with different fat/lean ratio (0.075, 0.250, and 0.330) and chopping duration (2, 5, and 8min) were obtained using a dedicated fiber optic prototype. Optical measurements were collected at three radial distances (2, 2.5, and 3mm) from the light source using a fiber optic spectrometer (300-1100nm). Light backscatter intensity decreased logarithmically with increasing fiber optic spacing. Light propagation through the emulsion decreased significantly with increasing chopping duration and fat concentration. Cooking loss increased with increasing fat/lean ratio and with under- or over-chopping. The maximum emulsion stability was observed at 5min of chopping. Several optically derived parameters were found to be significantly correlated with fat loss during cooking. Typically, those correlations were observed to increase with decreasing fiber distance. Based on these findings, an optical configuration is proposed that would compensate for the emulsion heterogeneity, maximizing the existing correlation between the optical signal and the emulsion quality metrics. PMID- 22064284 TI - 4-(1,3-Benzodioxol-5-yl)-2-oxo-1,2,5,6-tetra-hydro-benzo[h]quinoline-3-carbo nitrile. AB - In the mol-ecule of the title compound, C(21)H(14)N(2)O(3), the tetra-hydro benzo[h]quinoline fused-ring system is buckled owing to the ethyl-ene -CH(2)CH(2) fragment, the benzene ring and the pyridine ring being twisted by 24.3 (1) degrees . The ring of the benzodioxol system is bent away from the pyridine ring by 61.4 (1) degrees in order to avoid crowding the cyanide substituent. Two mol ecules are linked by a pair of N-H?O hydrogen bonds to form a centrosymmetric dimer. PMID- 22064286 TI - Intramuscular lipid and fatty acid profile of sheep comprising four sex-types and seven slaughter weights produced following commercial procedure. AB - The intramuscular lipid and fatty acid profiles of the m. longissimus dorsi from 84 sheep comprising four sex-types (enire ram, vasectomised ram, wether and ewe) and seven slaughter weights (32, 36, 40, 44, 48 and 52kg) were measured. Animals were reared following the commercial practice. Specifically, they were fed pasture and a concentrate diet, and age at slaughter ranged from 180 to 390 days. Differences between entire and vasectomised rams, and between wethers and ewes in intramuscular lipid content were not significant (P>0.05). However, entire and vasectomised rams were significantly lower (P<0.05) in intramuscular lipid content than ewes and wethers. Sex related differences in 14:0 (myristic acid), t18:1, c18:1, t18:2 and c18:2 proportions were not significant (P>0.05). Ewes and wethers were similar in 16:0 (palmitic acid) and 18:0 (stearic acid) proportions, but ewes contained significantly higher 16:0 and lower 18:0 proportions than entire and vasectomised rams (P<0.01). Entire and vasectomised rams recorded the highest c18:3 proportions, wethers were intermediate whilst ewes contained the lowest proportion (P<0.01). Although neither saturated fatty acid (SFA) nor monounsaturated fatty acid (MUFA) proportions varied with sex-type, vasectomised rams contained significantly higher polyunsaturated fatty acid (PUFA) proportion that the other sex-types (P<0.05). Whilst intramuscular lipid content, and 18:0 and c18:1 proportions were linearly correlated with slaughter weight (P<0.001), 14:0 and c18:3 proportions decreased quadratically with increasing slaughter weight (P<0.001). The vasectomised ram and the entire ram were similar in fatty acid profile, except the significantly higher PUFA proportion recorded by the vasectomised ram. PMID- 22064287 TI - Influence of oxygen exclusion and temperature on pathogenic bacteria levels and sensory characteristics of packed ostrich steaks throughout refrigerated storage. AB - Ostrich steaks (290) were obtained from Iliofibularis muscles. For microbiological and pH determinations, samples were inoculated with Listeria monocytogenes NCTC 11994 (80 steaks) or Escherichia coli ATCC 12806 (80), then air- or vacuum-packed and stored at either 4+/-1 degrees C or 10+/-1 degrees C. Analyses were carried out on days 0, 3, 6 and 9 of storage. For sensory evaluation, samples (130) were air- or vacuum-packed and stored at 4+/-1 degrees C or at 10+/-1 degrees C. Sensory attributes (odour, colour, drip loss, texture and general acceptability) were scored by six untrained judges using an unstructured nine-point hedonic scale on eleven sampling days (0, 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30). Increases in microbial counts (log(10)cfu/g) were observed throughout storage in all groups of samples for both L. monocytogenes (from 6.39+/-0.43-6.62+/-0.32 at day 0 to 8.87+/-0.19-9.64+/-0.43 at day 9) and E. coli (from 5.57+/-0.15-5.68-0.40 to 7.79+/-0.96-9.64+/-0.17). Gas atmosphere influenced microbial counts from day 3 of storage with lower (P<0.05) values observed in vacuum- than in air-packed samples at 10 degrees C (L. monocytogenes) or at 4 and 10 degrees C (E. coli). Storage temperature significantly influenced bacterial counts throughout storage, especially in air-packed samples. Lower pH values in vacuum- than in air-packed samples were observed from day 6. Both effects (gas atmosphere and temperature) influenced the hedonic scores, with higher values assigned to vacuum-packed samples for most attributes (with the exception of drip loss) and sampling days. A marked influence of storage temperature on sensorial scores was obtained in air-packaged ostrich steaks. The shelf-life (time until the average general acceptability score fell below 5) was 6 (air-packed samples), 9 (vacuum-packed, 10 degrees C), or 12 days (vacuum packed, 4 degrees C). The results being reported here suggest the importance of both oxygen exclusion and storage at low temperatures to reduce microbiological risks and improve the acceptability of ostrich meat. However, the short shelf life of this product highlights the need to keep the time between slaughter and sale to a minimum. PMID- 22064288 TI - Characterisation of fluorescent Schiff bases formed during oxidation of pig myofibrils. AB - The aim of this study was to investigate the formation of fluorescent Schiff bases between proteins and lipid oxidation products in myofibrils. Myofibrils were prepared from pig M. longissimus dorsi and oxidized by hydroxyl (OH()) and superoxide (O(2)(-)) radical generating systems. Protein oxidation was measured by the carbonyl content and lipid oxidation was estimated by measurement of thiobarbituric acid reactive substances (TBARS). To avoid any bias due to their low solubility, fluorescent pigments were estimated directly in the solid state by a front-face fluorescence technique. Hydroxyl radicals generated high levels of lipid and protein oxidation as well as fluorescent pigments, whereas only fluorescence was affected by superoxide radicals. The formation of fluorescent pigments was linked not only to aldehyde production, but also to the availability of the amino groups of the myofibrillar protein side chains. Schiff bases could be implicated in protein aggregation with deleterious effect on meat quality. PMID- 22064289 TI - Heat-induced gelation of porcine blood plasma proteins as affected by pH. AB - Porcine plasma is a by-product of the meat industry that can be used as a food ingredient. It is a protein mixture, hence its composition can be modified to meet specific functionality requirements. In the present paper, the gelation properties of plasma and its two major fractions (serum and albumin) have been studied at pH 4.5, 6.0 and 7.5. Polyacrylamide gel electrophoresis (SDS-PAGE) revealed that albumin was the constituent that remained soluble to a larger extent during heat-treatments, and that acidic coagulation occurred at pH 4.5, making weak interactions the predominating ones between protein aggregates. Differential scanning calorimetry (DSC) and rheological tests showed that both the thermal stability and the gelation point of protein solutions were lower as pH decreased. The textural properties and water-holding capacities of plasma and albumin gels were more pH-dependent than serum. Albumin gels were the weakest and those of plasma at pH 7.5, the strongest. It has been determined that interactions between protein fractions play a key role in the gelling properties due to synergistic effects. This knowledge should be useful in the engineering of a plasma derivative product designed for specific food requirements, by reformulating its natural composition and enhanced by controlling pH. PMID- 22064290 TI - The combined effect of antioxidants and modified atmosphere packaging on protein and lipid oxidation in beef patties during chill storage. AB - Effect of rosemary extract and ascorbate/citrate (1:1) in combination with modified atmosphere packaging (100% N(2), 80% O(2)/20% N(2)) on protein and lipid oxidation in minced beef patties during storage in the dark for up to 6 days at 4 degrees C was investigated. A high level of oxygen in the packaging atmosphere was found to increase both lipid and protein oxidation during storage as evaluated by TBARS analysis of secondary lipid oxidation products and by 2,4 dinitrophenylhydrazine derivatization of protein carbonyls. Both antioxidant systems tested were found to inhibit lipid oxidation but not protein oxidation. In contrast, ascorbate/citrate was found to promote protein oxidation. Rosemary extract was found to regenerate or protect alpha-tocopherol whereas the packaging atmospheres had no effect on alpha-tocopherol stability. In high oxygen atmospheres both antioxidants protected the fresh red meat colour with ascorbate/citrate being more efficient than the rosemary extract, whereas no effect of antioxidant on meat colour was found in beef patties stored in 100% nitrogen. PMID- 22064291 TI - Identification of meats from red deer (Cervus elaphus), fallow deer (Dama dama), and roe deer (Capreolus capreolus) using polymerase chain reaction targeting specific sequences from the mitochondrial 12S rRNA gene. AB - Polymerase chain reaction (PCR) based on oligonucleotide primers targeting the mitochondrial 12S rRNA gene was applied to the specific identification of meats from red deer (Cervus elaphus), fallow deer (Dama dama), and roe deer (Capreolus capreolus). The use of a common reverse primer, together with forward specific primers for red deer, fallow deer, and roe deer, allowed the selective amplification of the desired cervid sequences. The specificity of each primer pair was verified by PCR analysis of DNA from various game and domestic meats. The assay can be useful for the accurate identification of meats from cervid species, avoiding mislabeling or fraudulent species substitution in meat products. PMID- 22064292 TI - Indoor fattening of lambs raised on pasture. Part 1: Influence of stall finishing duration on lipid classes and fatty acids in the longissimus thoracis muscle. AB - Forty male Ile-de-France lambs (10 blocks of 4 homologous lambs) were used to study the effects of four feeding systems on muscle fatty acids (FA): raising and finishing on cool-season grasses (G), raising on the same grasses and stall finishing, indoors, on concentrates and hay, respectively, for 22 (GSS) or 41 days (GSL), and stall-feeding indoors on concentrates and hay during both growing and finishing periods (S). Twenty-four lambs only (6 blocks) were retained for comparison of growth performances, lipid content in the longissimus thoracis muscle (LT) and their FA composition according to treatment. The 16 other lambs (4 blocks) were removed from the comparison, due to a large spread in the growth of the lambs towards the end of the trial. No significant effects of treatment were seen on the rate of growth (221, 228, 243 and 245+/-SE 8.0g/d, respectively, for G, GSS, GSL and S groups), and the lipid contents of the LT (2.22, 2.16, 2.17 and 2.52+/-SE 0.11g/100g fresh tissue). Grazing, lowered n-6 PUFA (polyunsaturated fatty acids), and increased n-3 PUFA and C18:2 c9t11 (conjugated linoleic acid cis9, trans11) compared to concentrate feeding. The main effects of grazing were not removed by a short period of finish indoors on concentrate (GSS group), but C20:4 n-6 and C22:6 n-3 contents achieved the lowest contents in this group, with significant differences from the values observed for GSL and S groups (C20:4 n-6) or from the three other groups (C22:6 n-3). After a longer period of finish on concentrate (GSL group), C18:3 n-3 (linolenic acid), C18:2 c9t11 and long chain (LC) n-3 PUFA were brought to the levels observed in the S group. In terms of adequacy for human health, the C18:2 n-6/C18:3 n-3 ratios were favourably low in the four groups (2.6, 3.6, 4.9 and 5.2+/-SE 0.7, respectively, for G, GSS, GSL and S groups), the level observed in the case of G group being significantly lower than for the three other groups and the level observed for GSS group being significantly lower than for the GSL and S groups. PMID- 22064293 TI - Physical and chemical characteristics and acceptability of home style beef jerky. AB - Properties of snack foods from comminuted, seasoned beef, dried under laboratory conditions at a temperature of 55+/-2 degrees C were analyzed in this study. Samples were collected after 3, 4, 5, 6 and 7h of drying. The jerky products were evaluated by selected physicochemical and sensory methods. A significant influence of thermal treatment on the sample colour (L(*), a(*), b(*)-values) was observed. Results of sensory examination of selected attributes of the analyzed product performed by a trained panel confirmed that dried snack products obtained from beef under non-commercial conditions had the most desirable texture attributes, i.e. high chewiness at such a dryness that the moisture-to-protein ratio (MPR) was 0.5. At this value tensile work was the largest (757.77N*mm). Such a product is an attractive offer for those consumers who are willing to accept original, convenience products meeting at the same time their growing requirements concerning high organoleptic and nutritive value. PMID- 22064294 TI - Sodium diffusion in cured pork determined by (22)Na radiology. AB - A (22)Na-radioisotope method was developed as a non-destructive method for studying NaCl diffusion in meat. Scanning a well-defined cylindrical geometry with diffusion from one end gave reliable sodium diffusion profiles in meat. The diffusion coefficients derived from the profiles amounted to 5-7*10(-10)m(2)/s at 21 degrees C, largely in accordance with the general findings of the literature. Subsequent autoradiography carried out on the same samples demonstrated the feasibility of this method for validation of different experimental set-ups. The diffusion profiles were skewed showing a wall effect which, however, did not prevent consistent determination of the diffusion coefficient. The results suggest that the diffusion of salt in meat may depend on the individual animal. The present study appears to be the first to employ radioactive (22)Na as a tracer for NaCl diffusion in meat; it is concluded that the method is promising for studying salt diffusion in meat. PMID- 22064295 TI - Effect of social dominance on the meat quality of young Friesian bulls. AB - This study examined whether social status of the animals influenced the productive, morphological, physiological, and meat quality parameters in young Friesian bulls. The social dominance index (SDI) was estimated by direct observation of the dominance relationships among animals living in a feedlot. Thirty young bulls were divided into three groups based on their social status as assessed by SDI. The social status of the animals had a small effect on daily growth rate, but did not affect carcass or meat quality parameters. Physiological measures of stress were also unaffected by the animals' social status. PMID- 22064296 TI - Effect of cooking temperature and time on the physico-chemical, histological and sensory properties of female carabeef (buffalo) meat. AB - The effect of cooking temperature (80-100 degrees C) and time (30-60min) on collagen solubility of Semimembranosus muscle in carabeef were investigated. The pH, cooking loss, shear force value, collagen content, collagen solubility, sensory evaluation and histological observations of water bath cooked and pressure cooked Semimembranosus meat samples were measured. Increase in pH, cooking loss, collagen solubility and tenderness scores with decrease in shear force value and collagen content was observed with increases in cooking temperature and time. However, no statistical difference was observed for shear force values, collagen solubility values and tenderness scores in pressure cooked meat and meat cooked in a water bath at 100 degrees C for 45min, inferring that cooking of buffalo meat at 100 degrees C for 45min improved collagen solubility and tenderness to the same extent as that due to pressure cooking. PMID- 22064297 TI - Influence of myosin heavy- and light chain isoforms on early postmortem glycolytic rate and pork quality. AB - This study addressed the influence of the content of myosin heavy- (MHC) and light chain (MLC) isoforms on early postmortem glycolytic rate and meat quality traits in the porcine longissimus muscle. The fast-glycolysing group showed lower contents of MHC slow and MLC 1s isoforms (P<0.05), and higher MHC fast isoform contents than the normal-glycolysing group (P<0.05). The MHC fast/slow ratio was correlated with lactate content (r=0.41) and early postmortem muscle pH (r= 0.51), and the content of the MLC 1s isoform was negatively correlated with lactate content and glycolytic potential (r=-0.38 and -0.36, respectively). Hence, both the MHC and MLC isoforms did influence metabolite contents, thus also affecting glycolytic rate, and suggested that the myosin isoforms, in particular the MHC isoforms, might also have some bearing on the extent of protein denaturation and pork quality during the early postmortem period. PMID- 22064298 TI - Effects of fattening periods on the expression of adipogenic transcription factors in Wagyu beef cattle. AB - In this experiment, we studied the effects of fattening periods (at 19, 24, and 29 months of age) on the expression of the C/EBP family (C/EBPalpha, C/EBPbeta, and C/EBPdelta) and PPARgamma protein levels by Western blot analysis from different fat depots (subcutaneous, intermuscular, and mesenteric fat tissue) of Japanese Black steers. The expressions of C/EBPbeta-liver-enriched activator protein (LAP), which activates preadipocyte differentiation, in subcutaneous, intermuscular, and mesenteric fat tissue at 29 months of age were significantly lower than those at 19 months. On the other hand, the expressions of C/EBPbeta liver-enriched inhibitory protein (LIP), which represses preadipocyte differentiation, in subcutaneous and intermuscular fat tissue in 29 months of age were significantly higher than those at 19 months. The expressions of C/EBPalpha, which activates adipocyte terminal differentiation, in intermuscular fat tissue at 29 months of age were significantly higher than those at 19 months. No significant differences in the C/EBPdelta and PPAR gamma levels were observed in the fattening periods for any fat depots. These results suggest that adipogenic transcription factors, especially C/EBPbeta and C/EBPalpha, play an important role in regulating adipogenesis during the fattening periods of Japanese Black cattle. PMID- 22064299 TI - Biochemical and sensory characteristics of traditional fermented sausages of Vallo di Diano (Southern Italy) as affected by the use of starter cultures. AB - In this study, two strains of Staphylococcus xylosus isolated from traditional fermented sausages of Vallo di Diano (Southern Italy) were used in combination with an acidifying strain of Lactobacillus curvatus as starter culture for the production of fermented sausages. Two starter formulation were developed combining the proteolytic but not lipolytic (prt(+), lip(-)) S. xylosus CVS11 with the L. curvatus AVL3 (starter S1) and the S. xylosus FVS21 (prt(-), lip(+)) with the same strain of L. curvatus (starter S2). Proteolysis and lipolysis were observed during ripening by the increase in total free amino acids (FAA) and free fatty acids (FFA), respectively. Such activities were observed in both started and non started sausages (control). Moreover, the proteolytic and lipolytic activities were detected in products started by both formulations irrespective of the presence of such activities in the strains used. Therefore, it was not possible to conclude whether the effect of proteolysis and lipolysis during ripening of the started fermented sausages was due to the activity of the starter cultures or to the action of meat endogenous enzymes. PMID- 22064300 TI - Improved antioxidant activity of Vitamin E through solubilization in ethanol: A model study with ground beef. AB - Previous research has demonstrated that vitamin E (tocopherol) applied to muscle foods using an oil carrier targets the neutral lipid fraction (NLF: triacylglycerols) instead of the polar lipid fraction (PLF: phospholipids) and therefore does not act as an effective antioxidant. This paper demonstrates that delta-tocopherol (TOH) applied using a polar carrier was effectively incorporated into the PLF of ground beef and reduced subsequent TBARs development. TOH was incorporated in the PLF at 2820+/-231MUg TOH/g lipid and in the NLF at 167+/ 66.2MUg TOH/g lipid. Cooking ground beef (patties) did not result in loss of absolute amount of delta-tocopherol (5020+/-975MUg vs. 6220+/-1510MUg TOH, respectively). In addition, the development of thiobarbituric reactive substances (TBARs) in cooked product was significantly (p<0.05) lowered by TOH incorporation on days 2, 9, 15, and 22. PMID- 22064301 TI - Effect of mediterranean forest parasite with Curculio sp. on nutritional value of acorn for Iberian pig feeding and fat characteristics. AB - Sixteen Iberian barrows of the same age with an average initial live weight of 100.1kg were randomly distributed in two groups of eight pigs each. One group was fed healthy acorns and the other group received acorns infested of Curculio sp. The subcutaneous backfat from pigs fed healthy acorns had higher C18:1n-9, MUFA and C20:5n-3 and lower C18:0 and SFA proportions than that from the pigs fed acorns infested with Curculio. The consumption of acorns infested with Curculio sp. led to a reduction of C18:1n-9, MUFA, C18:2n-6, C18:3n-3, C22:5n-3 and PUFA proportions in neutral lipids from Longissimus dorsi muscle with respect to consumption of healthy acorns, whereas in polar lipids it produced a reduction in C18:1n-9, MUFA and C18:4n-3 proportions and an increase in C18:2n-6, C20:4n-6, n 6 and C20:5n-3 proportions and of n-6/n-3 ratio with respect to the healthy acorns consumption. The pigs fed healthy acorns had higher intramuscular fat percentage in Longissimus dorsi than pigs fed with acorns infested with Curculio (9.95 vs 7.09% SEM=0.60). PMID- 22064302 TI - Sonoelasticity to monitor mechanical changes during rigor and ageing. AB - We propose the use of sonoelasticity as a non-destructive method to monitor changes in the resistance of muscle fibres, unaffected by connective tissue. Vibrations were applied at low frequency to induce oscillations in soft tissues and an ultrasound transducer was used to detect the motions. The experiments were carried out on the M. biceps femoris muscles of three beef cattle. In addition to the sonoelasticity measurements, the changes in meat during rigor and ageing were followed by measurements of both the mechanical resistance of myofibres and pH. The variations of mechanical resistance and pH were compared to those of the sonoelastic variables (velocity and attenuation) at two frequencies. The relationships between pH and velocity or attenuation and between the velocity or attenuation and the stress at 20% deformation were highly correlated. We concluded that sonoelasticity is a non-destructive method that can be used to monitor mechanical changes in muscle fibers during rigor-mortis and ageing. PMID- 22064303 TI - The effect of nisin on L. monocytogenes in Turkish fermented sausages (sucuks). AB - Turkish fermented sausage (sucuk) is a traditional, well-known meat product in Turkey. The aim of this study was to evaluate the effect of different nisin concentrations on Listeria monocytogenes in experimentally contaminated sucuk. Analyses were performed on at 0, 1, 3, 5, 7, 10, 15, 20, 25 and 30days for L. monocytogenes and other microbiological parameters (Total mesophilic aerobic bacteria and lactic acid bacteria) and physico-chemical parameters (pH, a(w) and moisture content).The sucuk dough was contaminated with L. monocytogenes ATCC 7644 at a concentration of 10(6)cfu/g, and the dough was divided into six equal groups. Each group was treated separately with different nisin concentrations (0, 5, 10, 25, 50 and 100MUg/g). No L. monocytogenes surviving cells were detected in groups which contained 100MUg/g and 50MUg/g nisin at day 20 and 25, respectively (p<0.001). In conclusion, the inhibition of L. monocytogenes in sucuk increases with the increasing concentrations of nisin. PMID- 22064304 TI - Effect of Iberian*Duroc genotype on dry-cured loin quality. AB - Dry-cured loins from three different pig genotypes were studied: GEN1: ? Iberian*? Duroc1, GEN2: ? Duroc1*? Iberian; GEN3: ? Duroc2*? Iberian. GEN1 and GEN2 are reciprocal crosses, while the difference between GEN2 and GEN3 is the Duroc sire line. The genotype of pigs Duroc1 was selected for the manufacture of dry-cured meat products, while the genotype Duroc2 was selected for meat production. The chemical composition of the dry-cured loins was significantly different, especially the intramuscular fat (IMF) content which was highest in GEN2. Dry-cured loins from GEN3 showed lower CIE a(*) and chroma values. IMF from GEN2 was more saturated whereas GEN3 had higher percentages of PUFA and MUFA. Loins from GEN3 had higher TBA-RS values (p>0.05) and hexanal contents. Loins from GEN3 had higher Warner-Bratzler shear force (p>0.05) and instrumental hardness than those from GEN2, being intermediate in GEN1. Panellists considered that loins from GEN2 were more marbled, more odorous, juicier, sweeter and less salty than loins from GEN3. Therefore, loins from GEN2 had the best quality, followed by GEN1, while GEN3 had the worst quality. PMID- 22064305 TI - In vitro and in vivo studies of creatine monohydrate supplementation to Duroc and Landrace pigs. AB - Duroc and Landrace pigs as well as primary myotubes from these breeds were used to investigate mechanisms behind differences in their response to creatine monohydrate (CMH). Pigs were supplemented with 0, 12.5, 25 or 50g CMH/d for 5 days (n=10 per treatment and breed). Plasma levels of creatine increased dose dependently in both breeds, while muscle-creatine phosphate content increased only in the Duroc pigs. (1)H NMR metabolic profiling showed a tendency towards clustering according to CMH supplementation only among Duroc pigs, revealing a stronger response compared to Landrace pigs. The abundance of insulin-like growth factor I and myostatin mRNA was decreased by CMH supplementation while that of type 1 IGF-receptor and creatine transporter was unaffected. Protein synthesis, increased in the myotubes from both breeds, indicating protein accretion, but no effect was observed on the mRNA abundance of IGF-I, type 1 IGF-receptor, myostatin or the creatine transporter in myotubes. PMID- 22064306 TI - Some qualitative and chromatic aspects of thawed buffalo (Bubalus bubalis) meat. AB - After thawing, the meat of beef calves (Italian Frisian breed) and buffalo calves (Mediterranean breed) slaughtered at 4, 8 and 12 months of age was examined. Both the pH and the thawing loss confirmed that the meat of buffalo calves is more suitable for preservation by freezing. With increased age and time of exposure to air the lightness of the non-renewed surface was reduced. The lightness of the fresh cut surface remained stable in the various thawing phases though it was less in the older animals. The a(*) index increased with animal age but decreased during the 4 days post-thawing. The fresh cut surface of buffalo meat from calves slaughtered at 4 and 8 months was not darker than beef slaughtered at the same age. On the contrary at 12 months of age, the buffalo meat had a lower redness index than beef and a higher haematin concentration. PMID- 22064307 TI - Rate and extent of pH decline affect proteolysis of cytoskeletal proteins and water-holding capacity in pork. AB - The objective of this study was to determine the extent to which early postmortem (PM) pH decline influences proteolysis of the intermediate filament protein desmin, the costameric proteins vinculin and talin and autolysis of MU-calpain in the longissimus muscle (LM) of pigs from two genetic lines. Based on the LM 3h pH (H=3h pH of LM>6.0; L=3h pH of LM pH<5.7) PM, 10 carcasses per line and pH group were selected. The average 3h pH within pH group was 6.23 (H) and 5.44 (L). The LM samples were collected 24, 48, 72, and 120h PM and percent drip loss was measured after 1, 2, and 4d of storage. Samples collected at 24, 48, 72, and 120h PM were used to monitor desmin, vinculin, and talin degradation and samples collected at 24h PM were used to determine the extent of MU-calpain autolysis by immunoblotting. Higher (P<0.01) pH values at 45min, 6h, and 24h PM and lower (P<0.01) drip losses after 1, 2, and 4d of storage were recorded in the H compared to the L-group. Abundance of the 76kDa MU-calpain autolysis product was greater (P<0.01), proteolysis of talin at all measured time points and proteolysis of desmin after 24 and 48h PM was greater (P?0.03) in the H-group than in the L-group. The current findings indicate activation rate of MU-calpain may be associated with proteolysis of desmin and talin and could play a role in the development of drip loss. The rate of early PM pH decline can partly explain the variation of desmin and talin degradation by affecting the activation of MU calpain. PMID- 22064308 TI - Growth, yield of carcass and biochemical composition of meat and fat in nutria (Myocastor coypus) reared in an intensive production system. AB - Growth, carcass yield and proximate composition were determined in intensively reared nutria (Myocastor coypus) fed different levels of protein. Growth, food intake and food utilization efficiency were not significantly affected, within the same sex, in animals receiving 16%, 19% or 22% of protein in the diet. Males consumed the same amount of food as females but had greater live and carcass weights at slaughter age than females. Males had the highest meat yield and females had the highest fat content. Independent of dietary protein level, the pectoral muscles of all animals ranged from 19.2% to 23.6% protein, 1.97% to 2.47% total lipids, and 70.1 to 72.0mg of cholesterol in 100g of tissue. In the thigh muscles, the observed ranges were between 21.4% and 22.9% in proteins, 1.83% and 2.07 in total lipids and 69.9 and 71.0mg of cholesterol in 100g of tissue. The determination of classes of lipids shows more phospholipids contents in animals receiving 16% of protein in diet. PMID- 22064309 TI - Nutritional and sensory quality of porcine raw meat, cooked ham and dry-cured shoulder as affected by dietary enrichment with docosahexaenoic acid (DHA) and alpha-tocopheryl acetate. AB - The effects of dietary enrichment of pig diets with DHA from a marine source (Algatrium((r))) and alpha-tocopheryl acetate on the nutritional and sensory characteristics of pork and pork products were evaluated. Raw and cooked hams, and dry-cured shoulders from pigs fed with three diets (control, control supplemented with 0.3% DHA plus 50ppm alpha-tocopheryl acetate and control with 200ppm alpha-tocopheryl acetate) were used. The treatments did not cause any significant differences in proteolytic and antioxidant enzyme activities, except on catalase (CAT) which increased significantly in raw hams from pigs fed DHA supplemented diets. Vitamin E accumulated in samples with alpha-tocopheryl acetate supplementation. DHA added to the diet increased the DHA level by 87% compared with the control treatment in both raw and dry-cured shoulders, and exceeded 82% in cooked hams. In consequence, the incorporation of the n-3 source in the diet significantly reduced the n-6/n-3 ratio in all products. The ratio reduction ranged from 51% in dry-cured shoulders to 65% in cooked and raw hams. No significant differences were found among treatments in the sensory parameters evaluated in the cooked hams. Fishy odour and flavour were not detected in any sample by the trained panel. However, reduced cured and aged flavours and a stronger fishy flavour were found in dry-cured shoulders from pigs on the DHA enriched treatment; while, alpha-tocopheryl acetate supplementation had negligible influence on flavour. PMID- 22064310 TI - Direct demonstration of the presence of zinc in the acetone-extractable red pigment from Parma ham. AB - We studied the presence of zinc in the red pigment extracted from Parma ham by scanning electron microscopy/energy dispersive X-ray microanalysis. The large peak of about 8.6keV and the small peaks at about 1.1keV and 9.5keV were derived from K(alpha), L(alpha1) and K(beta) X-ray of zinc, respectively. Thus, the results suggested that zinc existed in the red pigment extracted from Parma ham. In contrast, the K(alpha) X-ray peak of iron (6.4keV) was not detected and the K(alpha) X-ray peak of magnesium (1.3keV) was hardly detected. These results revealed that the red pigment contained not iron but zinc. In addition to the results of mass analysis in previous studies, the red pigment was demonstrated to be zinc protoporphyrin IX. PMID- 22064312 TI - Comment on: "Characterization of maternal transfer of decabromodiphenyl ether (BDE-209) administered to pregnant Sprague-Dawley rats". PMID- 22064315 TI - Understanding the potential and challenges of adenoma treatment as a prevention opportunity: insights from the BeWEL formative study. AB - OBJECTIVES: To explore prevention opportunities presented by colorectal adenoma diagnosis and inform engagement strategies for the BeWEL study (body weight and physical activity lifestyle intervention for colorectal cancer screening participants who have undergone adenoma removal). METHODS: Qualitative study comprising 4 purposively sampled focus groups conducted in urban and rural areas in Tayside, Scotland, with different deprivation levels. Participants were men and women (n=17) aged 50-74 with BMI>25 kg/m(2) with removal of adenoma detected by colorectal cancer screening. RESULTS: Adenoma diagnosis presents both opportunities and challenges for prevention. Some patients perceived adenoma as minor and not sufficiently motivating to act as a 'teachable moment'. Patients had low awareness of the relationship between adenoma and lifestyle factors, and received little information on prevention during screening and treatment. Consequently they interpreted post-treatment 'all clear' messages as validation of existing lifestyles, and did not see the relevance of prevention advice. Receptiveness increased when the association between lifestyle, adenoma recurrence and other illness was explained. CONCLUSION: The study illustrates the value of exploratory research into patient understanding to improve communications and health services. Without unduly worrying patients, professionals should explain how to reduce risk of adenoma, cancer and other diseases, particularly through diet, physical activity and weight reduction. PMID- 22064316 TI - An observational study on socio-economic and ethnic differences in indicators of sedentary behavior and physical activity in preschool children. AB - OBJECTIVE: We studied associations between social disadvantage and indicators of sedentary behavior and physical activity at preschool age. METHODS: Data from 4688 children enrolled in a birth cohort in Rotterdam, the Netherlands, between 2002 and 2006 were analyzed. Indicators of sedentary behavior (watching television >= 2 h/day and sitting in a buggy >= 0.5 h/day) and physical inactivity (playing outside < 3 h/day) were measured by a parent-reported questionnaire at age 3. Adjustments were made for social circumstances and indicators of health behaviors. Logistic regression was used to obtain odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Children with low educated mothers (OR: 3.27, 95% CI 2.12-5.05) and non-Dutch children (OR(nonWestern): 2.67, 95% CI 2.04-3.49, OR(Western): 2.09, 95% CI 1.42-3.0) were more likely to watch television for at least 2 h/day. Similar results were seen for sitting in a buggy for at least 0.5h/day. Non western children were more likely to play outside for less than 3 h/day (OR: 1.95, 95% CI: 1.39-2.73) than native Dutch children, while no differences were seen for other western children or children from mothers with a low educational level. CONCLUSIONS: Socio economic status and ethnicity are already associated with indicators of sedentary lifestyles at preschool age. PMID- 22064317 TI - Storytelling to access social context and advance health equity research. AB - OBJECTIVE: Increased understanding of individual and social determinants of health is crucial to moving toward health equity. This essay examines storytelling as a vehicle for advancing health equity research. METHOD: Contemplative examination of storytelling as a research strategy. RESULTS: An overview of story theory is provided. This is followed by an examination of storytelling as a tool for increasing understanding about the contexts in which people negotiate health, strengthening participation of communities in addressing health issues, and building bridges between researchers and target populations. CONCLUSION: Storytelling can be a powerful tool for advancing health equity research. However, its effective use requires a renegotiation of relationships between researchers and target communities, as well as setting aside routine time to attend storytelling events and read a variety of stories. PMID- 22064318 TI - The function of integrin-linked kinase in normal and activated stellate cells: implications for fibrogenesis in wound healing. AB - Integrin-linked kinase (ILK) is a multidomain focal adhesion protein implicated in signal transduction between integrins and growth factor/extracellular receptors. We have previously shown that ILK expression is increased in liver fibrosis and that ILK appears to be a key regulator of fibrogenesis in rat hepatic stellate cells, effectors of the fibrogenic response. Here we hypothesized that the mechanism by which ILK mediates the fibrogenic phenotype is by engaging the small GTPase, Rho in a signal transduction pathway linked to fibrogenesis. ILK function in quiescent (non-fibrogenic) and activated (fibrogenic) stellate cells was examined in cells isolated from rat livers. ILK, Rho, and Galpha(12/13) signaling were manipulated using established chemical agents or specific adenoviral constructs. ILK activity was minimal in quiescent stellate cells, but prominent in activated stellate cells; inhibition of ILK activity had no effect in quiescent cells, but had prominent effects in activated cells. Overexpression of ILK in activated stellate cells increased Rho activity, but had no effect in quiescent cells. Further, endothelin-1 stimulated Rho activity in activated stellate cells, but not in quiescent cells. Rho, Rho guanine nucleotide exchange factors, and Galpha(12/13) expression were increased after stellate cell activation. Inhibition of Galpha(12/13) signaling, by expression of the RGS domain of the p115-Rho-specific GEF (p115-RGS) in activated stellate cells, significantly inhibited type I collagen and smooth muscle alpha actin expression, both classically upregulated after stellate cell activation. The data suggest that ILK mediates Rho-dependent functional effects in activated stellate cells, and raise the possibility that ILK is important in cross-talk with the G-protein-coupled receptor system. PMID- 22064319 TI - Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms. AB - Although large cholangiocytes exert their functions by activation of cyclic adenosine 3',5'-monophosphate (cAMP), Ca(2+)-dependent signaling regulates the function of small cholangiocytes. Histamine interacts with four receptors, H1 H4HRs. H1HR acts by Galphaq activating IP(3)/Ca(2+), whereas H2HR activates Galpha(s) stimulating cAMP. We hypothesize that histamine increases biliary growth by activating H1HR on small and H2HR on large cholangiocytes. The expression of H1-H4HRs was evaluated in liver sections, isolated and cultured (normal rat intrahepatic cholangiocyte culture (NRIC)) cholangiocytes. In vivo, normal rats were treated with histamine or H1-H4HR agonists for 1 week. We evaluated: (1) intrahepatic bile duct mass (IBDM); (2) the effects of histamine, H1HR or H2HR agonists on NRIC proliferation, IP(3) and cAMP levels and PKCalpha and protein kinase A (PKA) phosphorylation; and (3) PKCalpha silencing on H1HR stimulated NRIC proliferation. Small and large cholangiocytes express H1-H4HRs. Histamine and the H1HR agonist increased small IBDM, whereas histamine and the H2HR agonist increased large IBDM. H1HR agonists stimulated IP(3) levels, as well as PKCalpha phosphorylation and NRIC proliferation, whereas H2HR agonists increased cAMP levels, as well as PKA phosphorylation and NRIC proliferation. The H1HR agonist did not increase proliferation in PKCalpha siRNA-transfected NRICs. The activation of differential signaling mechanisms targeting small and large cholangiocytes is important for repopulation of the biliary epithelium during pathologies affecting different-sized bile ducts. PMID- 22064320 TI - A novel murine model for non-alcoholic steatohepatitis developed by combination of a high-fat diet and oxidized low-density lipoprotein. AB - Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome that is characterized by steatosis, inflammation, and fibrosis, and may progress to cirrhosis and carcinoma. To investigate its pathogenic processes, we established a novel murine model for NASH by combination of a high-fat diet (HFD) and oxidized low-density lipoprotein (oxLDL). Mice that received HFD for 23 weeks showed hepatic steatosis, slight fibrosis, and a high level of lipid peroxidation compared with a regular diet (RD)-fed mice. Hepatic injury and elevated tumor necrosis factor (TNF)-alpha mRNA expression were also detected in these mice. Moreover, oxLDL administration to HFD-fed mice during weeks 21-23 not only aggravated hepatic steatosis, fibrosis, and lipid metabolism, but also resulted in intense inflammation, including severe hepatic injury and inflammatory cell infiltration, which are the typical histological features of NASH. Inflammation was accompanied by increased gene expression of TNF-alpha and interleukin (IL)-6. Additionally, the livers of RD-fed animals treated with oxLDL during weeks 21-23 were characterized by foamy macrophages and inflammatory cell infiltration along with an elevated IL-6 mRNA level. These results suggest that an increased oxidative state, including HFD-induced intracellular lipid peroxidation and its extracellular source from oxLDL, is the actual trigger for hepatic inflammation in which liver injury is mediated by TNF-alpha and inflammatory cell accumulation is dependent on IL-6. HFD and oxLDL also induced insulin resistance in mice; additionally, oxLDL downregulated insulin secretion. In this model, CD36 overexpression was observed in the hepatocytes of HFD-fed mice and those treated with HFD and oxLDL, and in the hepatic macrophages of RD-fed mice immediately after oxLDL treatment. In vitro experiments indicated a rapid and transient elevation of CD36 on macrophage plasma membrane in response to oxLDL. Our findings demonstrate that CD36 expressed on hepatocytes and hepatic macrophages mediates the pathophysiology of NASH. PMID- 22064321 TI - ERp29 induces breast cancer cell growth arrest and survival through modulation of activation of p38 and upregulation of ER stress protein p58IPK. AB - Endoplasmic reticulum protein 29 (ERp29) is an ER luminal protein that has a role in protein unfolding and secretion, but its role in cancer is unclear. Recently, we reported that overexpression of ERp29 significantly inhibited cell proliferation and prevented tumorigenesis in highly proliferative MDA-MB-231 breast cancer cells. Here, we show that ERp29-induced cancer cell growth arrest is modulated by the interplay between the concomitant phosphorylation of p38 and upregulation of the inhibitor of the interferon-induced, double-stranded RNA activated protein kinase, p58(IPK). In this cell model, ERp29 overexpression significantly downregulates modulators of cell proliferation, namely urokinase plasminogen activator receptor, beta(1)-integrin and epidermal growth factor receptor. Furthermore, ERp29 significantly (P<0.001) increases phosphorylation of p38 (p-p38) and reduces matrix metalloproteinase-9 secretion. The role of ERp29 in upregulating cyclin-dependent kinase inhibitors (p15 and p21) and in downregulating cyclin D(2) is demonstrated in slowly proliferating ERp29 overexpressing MDA-MB-231 cells, whereas the opposite response was observed in ERp29-knockdown MCF-7 cells. Pharmacological inhibition of p-p38 downregulates p15 and p21 and inhibits eIF2alpha phosphorylation, indicating a role for p-p38 in this process. Furthermore, p58(IPK) expression was increased in ERp29 overexpressing MDA-MB-231 cells and highly decreased in ERp29-knockdown MCF-7 cells. This upregulation of p58(IPK) by ERp29 suppresses the activation of p p38/p-PERK/p-eIF2alpha by repressing eIF2alpha phosphorylation. In fact, reduction of p58(IPK) expression by RNA interference stimulated eIF2alpha phosphorylation. The repression of eIF2alpha phosphorylation by p58(IPK) prevents ERp29-transfected cells from undergoing ER-dependent apoptosis driven by the activation of ATF4/CHOP/caspase-3. Hence, the interplay between p38 phosphorylation and p58(IPK) upregulation has key roles in modulating ERp29 induced cell-growth arrest and survival. PMID- 22064322 TI - Bis(cyanamide-kappaN)[4-(1H-imidazol-1-yl)phenol-kappaN]bis-(nitrato kappaO)copper(II). AB - A pair of linear cyanamide (NCNH(2)) ligands, two monodentate 4-(1H-imidazol-1 yl)phenol (L) ligands and two nitrate anions link the Cu(II) atom into a mononuclear unit, [Cu(NO(3))(2)(C(9)H(8)N(2)O)(2)(NCNH(2))(2)]. The coordination polyhedron of the Cu atom is an elongated octa-hedron distorted by Jahn-Teller effects. Inter-molecular O-H?O, O-H?N, N-H?O and N-H?N hydrogen-bonding inter actions link these units into a three-dimensional supra-molecular architecture. PMID- 22064323 TI - Estimation of glomerular filtration rate in calves using the contrast medium iodixanol. AB - To develop a simple procedure for estimating glomerular filtration rate (GFR) in calves, a three-sample method using iodixanol was first compared to that using the standard agent inulin. Iodixanol and inulin were co-administered intravenously to calves at 40 mg I/kg and 40 mg/kg, respectively, and blood was collected 30, 60, 120, and 180 min later. Serum iodixanol and inulin concentrations were separately determined by high performance liquid chromatography and colorimetry. Serum urea nitrogen (UN) and creatinine concentrations were also measured. GFR estimated by iodixanol was consistent with that using inulin in clinically healthy calves. Based on GFR estimations in healthy calves and those renal-loaded with iodixanol, it was found that the serum creatinine concentrations became elevated when GFR decreased to 60% of the reference value. In contrast, serum UN concentrations fluctuated widely, presumably due to extra-renal factors. When GFR was estimated using the three sample method and compared with the single-blood-sample method, 62/69 (90%) of samples tested were within the agreement plots. The results demonstrated that the single-blood-sample method using iodixanol may be useful in monitoring GFR in calves. PMID- 22064324 TI - Bone morphogenic protein-4 induces endothelial cell apoptosis through oxidative stress-dependent p38MAPK and JNK pathway. AB - The expression of bone morphogenic protein 4 (BMP4), a new pro-inflammatory marker, is increased by disturbed flow in endothelial cells (ECs). BMP4 stimulates production of reactive oxygen species (ROS) and causes endothelial cell dysfunction. The present study examined BMP4-induced apoptosis in ECs and isolated arteries from rat, mouse, and human, and the signaling pathways mediating BMP4-induced apoptosis. Apoptosis was assessed by flow cytometry to detect Annexin-V positive cells, and terminal deoxynucleotidyl transferase dUTP nick end (TUNEL) labeling. The superoxide production was measured by dihydroethidium fluorescence. BMP4 induced EC apoptosis in human mesenteric arteries, mouse aortic endothelium, rat primary ECs, and human ECs. BMP4-induced EC apoptosis was mediated through ROS production by activation of NADPH oxidase, which led to cleaved caspase-3 expression. BMP4 also induced sequential activation of p38 MAPK and JNK which was upstream of caspase 3 activation. Knockdown of BMP receptor 1A by lentiviral shRNA or NOX4 siRNA transfection inhibited BMP4-induced ROS production, p38 and JNK phosphorylation, and caspase-3 activation in ECs. JNK siRNA inhibited BMP4-induced JNK phosphorylation and caspase-3 activation. The present study delineates that BMP4 causes EC apoptosis through activation of caspase-3 in a ROS/p38MAPK/JNK-dependent signaling cascade. PMID- 22064325 TI - Cardiomyocyte calcineurin signaling in subcellular domains: from the sarcolemma to the nucleus and beyond. AB - The serine-threonine phosphatase calcineurin is activated in cardiac myocytes in the diseased heart and induces pathological hypertrophy. Calcineurin activity is mainly triggered by calcium/calmodulin binding but also through calpain mediated cleavage. How controlled calcineurin activation is possible in cardiac myocytes, which typically show a 10-fold difference in cytosolic calcium concentration with every heartbeat, has remained enigmatic. It is now emerging that calcineurin activation and signaling occur in subcellular microdomains, in which it is brought together with target proteins and exceedingly high concentrations of calcium in order to induce downstream signaling. We review current evidence of subcellular calcineurin mainly at the sarcolemma and the nucleus, but also in association with the sarcoplasmic reticulum and mitochondria. We also suggest that knowledge about subcellular signaling could help to develop inhibitors of calcineurin in specific microdomains to avoid side-effects that may arise from complete calcineurin inhibition. PMID- 22064326 TI - Local signalling in myocytes. PMID- 22064327 TI - Methods of assessment of magnesium status in humans: a systematic review. AB - To understand humans' requirements for magnesium and the effect of magnesium on health, it is important to identify sensitive and population-specific biomarkers of magnesium status. Thus, we assessed the effectiveness of different magnesium status biomarkers through a systematic review of published magnesium supplementation and depletion trials in healthy humans. The methods used in this study included a structured search on Ovid MEDLINE, EMBASE (Ovid) and Cochrane databases up to September 2008, followed by the use of formal inclusion/exclusion criteria, data extraction, validity assessment, and meta-analysis. A total of 20 potential biomarkers of magnesium status were assessed from 21 included publications. The majority of studies included were magnesium supplementation studies. Fewer magnesium depletion studies were identified. Available data analysis suggests that serum/plasma magnesium concentration, red blood cell (RBC) concentration and urinary magnesium excretion responded to dietary manipulation. For other biomarkers with available data, it was not possible to draw any conclusions about their usefulness as magnesium status biomarkers. The lack of data prevented detailed subgroup analysis. In conclusion, although limited data were available, serum/plasma magnesium concentration, RBC magnesium concentration and urinary magnesium excretion appear to be useful biomarkers of magnesium status in the general population. Further high-quality studies are needed to assess the effectiveness of existing and newly developed biomarkers, especially in populations that are vulnerable to magnesium deficiency. PMID- 22064328 TI - Specialty outpatient care of diabetic patients in Poland--are we far from treatment targets? Rationale, design, and preliminary results of the OPTIMO study. AB - INTRODUCTION: While clinical practice guidelines reflect the best known evidence based approach to patient care, it is individual clinicians and patients who make decisions and treatment choices, and individual patients who actually achieve (or not) the treatment goals. OBJECTIVES: The aim of the study was to describe the population of diabetic patients attending specialty outpatient clinics, to characterize the management of patients with different types of diabetes, and to assess the accordance of management with the recommendations developed by Diabetes Poland. PATIENTS AND METHODS: The OPTIMO observational study was conducted from 2006 to 2009 and included patients with diabetes diagnosed according to the 1999 World Health Organization criteria who were observed for 1 to 3 years, with control visits at least every 6 months. Participating physicians used pocket PCs equipped with specially developed software to collect patients' data and to provide educational reminders to clinicians. RESULTS: The final analysis involved 9600 patients for whom valid baseline questionnaires were available. Type 2 diabetes was observed in 92% and type 1 diabetes in 6% of the patients. Mean age was 60.5 years. Women constituted 54% of the population. Coronary heart disease was observed in 32% and arterial hypertension in 76% of the patients. At baseline, 23% of the patients had hemoglobin A1c level below 6.5% and 44% below 7.0. Total cholesterol and triglycerides treatment goals were met at baseline by slightly more than half of the patients, while low-density lipoprotein cholesterol treatment goal was met only by 33% of the patients. Baseline blood pressure below 130/80 mmHg was reported for 11% of the patients. CONCLUSIONS: At the beginning of the OPTIMO study, we have observed considerable deviations from treatment targets recommended by current clinical practice guidelines for diabetic patients, which leaves significant room for improvement in the care of diabetic patients. PMID- 22064329 TI - Role of base-excision repair in the treatment of childhood acute lymphoblastic leukaemia with 6-mercaptopurine and high doses of methotrexate. AB - Methotrexate (MTX) and 6-mercaptopurine (6MP) are the most commonly used drugs in the therapy of childhood acute lymphoblastic leukaemia (ALL). The main genotoxic effect of MTX resulting from inhibition of thymidylate synthase is mis incorporation of uracil into DNA, which is considered essential for the effectiveness of the Protocol M in ALL IC BFM 2002/EURO LB 2002 regimens. In this study, we investigated the level of basal and induced DNA damage as well as the effectiveness of DNA repair in lymphocytes of children with ALL at four time points during therapy with MTX and 6MP. To assess DNA damage and the efficacy of DNA repair we used the modified alkaline comet assay with uracil DNA glycosylase (Udg) and endonuclease III (EndoIII). In addition, we examined the induction of apoptosis in the lymphocytes of the patients during treatment. Finally, we compared the activity of base-excision repair (BER), involved in removal of both uracil and oxidized bases from DNA in lymphocytes of children with ALL and lymphocytes of healthy children. BER efficiency was estimated in an in vitro assay with cellular extracts and plasmid substrates of heteroduplex DNA with an AP-site. Our results indicate that there is a significant decrease in the efficacy of DNA repair associated with an increased level of uracil in DNA and induction of apoptosis during therapy. Moreover, it was found that the BER capacity was decreased in the lymphocytes of ALL patients in contrast to that in lymphocytes of healthy children. Thus, we suggest that an impairment of the BER pathway may play a role in the pathogenesis and therapy of childhood ALL. PMID- 22064330 TI - Treadmill running frequency on anxiety and hippocampal adenosine receptors density in adult and middle-aged rats. AB - Physical exercise protocols have varied widely across studies raising the question of whether there is an optimal intensity, duration and frequency that would produce maximal benefits in attenuating symptoms related to anxiety disorders. Although physical exercise causes modifications in neurotransmission systems, the involvement of neuromodulators such as adenosine has not been investigated after chronic exercise training. Anxiety-related behavior was assessed in the elevated plus-maze in adult and middle-aged rats submitted to 8 weeks of treadmill running 1, 3 or 7 days/week. The speed of running was weekly adjusted to maintain moderate intensity. The hippocampal adenosine A1 and A2A receptors densities were also assessed. Treadmill running protocol was efficient in increasing physical exercise capacity in adult and middle-aged rats. All frequencies of treadmill running equally decreased the time spent in the open arms in adult animals. Middle-aged treadmill control rats presented lower time spent in the open arms than adult treadmill control rats. However, treadmill running one day/week reversed this age effect. Adenosine A1 receptor was not changed between groups, but treadmill running counteracted the age-related increase in adenosine A2A receptors. Although treadmill running, independent from frequency, triggered anxiety in adult rats and treadmill running one day/week reversed the age-related anxiety, no consistent relationship was found with hippocampal adenosine receptors densities. Thus, our data suggest that as a complementary therapy in the management of mental disturbances, the frequency and intensity of physical exercise should be taken into account according to age. Besides, this is the first study reporting the modulation of adenosine receptors after chronic physical exercise, which could be important to prevent neurological disorders associated to increase in adenosine A2A receptors. PMID- 22064333 TI - Small intestinal bacterial overgrowth and lactose intolerance contribute to irritable bowel syndrome symptomatology in Pakistan. AB - BACKGROUND /AIM: The symptoms of irritable bowel syndrome resemble those of small intestinal bacterial overgrowth (SIBO). The aim of this study was to determine the frequency of SIBO and lactose intolerance (LI) occurrence in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) according to Rome III criteria. PATIENTS AND METHODS: In this retrospective case-control study, patients over 18 years of age with altered bowel habit, bloating, and patients who had lactose Hydrogen breath test (H 2 BT) done were included. The "cases" were defined as patients who fulfill Rome III criteria for IBS-D, while "controls" were those having chronic nonspecific diarrhea (CNSD) who did not fulfill Rome III criteria for IBS-D. Demographic data, predominant bowel habit pattern, concurrent use of medications, etc., were noted. RESULTS: Patients with IBS-D were 119 (51%) with a mean age of 35 +/- 13 years, while those with CNSD were 115 (49%) with mean age 36 +/- 15 years. Patients in both IBS-D and CNSD were comparable in gender, with male 87 (74%) and female 77 (64%). SIBO was documented by lactose H2BT in 32/234 (14%) cases. It was positive in 22/119 (19%) cases with IBS-D, while 10/115 (9%) cases had CNSD (P = 0.03). LI was positive in 43/234 (18%) cases. Of these, 25/119 (21%) cases had IBS-D and 18/115 (16%) cases had CNSD (P = 0.29). CONCLUSION: SIBO was seen in a significant number of our patients with IBS-D. There was no significant age or gender difference in patients with or without SIBO. PMID- 22064334 TI - Metabolic syndrome frequency in inflammatory bowel diseases. AB - BACKGROUND/AIM: Metabolic syndrome (MetS) is a clinical condition characterized by central obesity, elevated triglycerides, low-high density lipoproteins, impaired fasting glucose, and hypertension. There is insufficient data on the prevalence of MetS in patients with inflammatory bowel disease (IBD). This study sought to determine the prevalence of MetS in a Turkish cohort of patients with IBD and the association between insulin resistance (IR) and the MetS parameters, in this population. PATIENTS AND METHODS: A total of 177 patients over 18 years of age (62 with Crohn's disease (CD) and 115 with ulcerative colitis (UC)) were enrolled in the study. The presence of at least three criteria of the International Diabetes Federation (IDF) was accepted for the diagnosis of MetS. The Homeostasis Model Assessment (HOMA) was used to determine IR. HOMA values < 1 were considered normal and values > 2.5 indicated a high probability of IR. RESULTS: MetS frequency was higher in patients n=34 (29.5%) with UC than in patients n=11 (17.7%) with CD (P < 0.01). MetS was detected in 12 of the 117 patients (10.3%) with IBD, under 45 years of age, and in 33 of 60 patients (55%) over 45 years of age. HOMA value in n=31 patients (27%) with UC was > 2.5. Body mass index, insulin (P < 0.001), waist circumference, fasting plasma glucose, leukocyte count (P < 0.01), triglycerides, C-reactive protein, and uric acid values (P < 0.05) were significantly higher in UC patients with IR than those without IR. CONCLUSION: Frequent occurrence of MS with increasing age in IBD, particularly in UC, showed the importance of early diagnosis and treatment of cardiovascular disease risk factors in the long-term follow-up of these diseases. PMID- 22064335 TI - Prevalence of microscopic colitis in patients with chronic diarrhea in Egypt: a single-center study. AB - BACKGROUND/AIM: Microscopic colitis (MC) is diagnosed when a patient with chronic watery non-bloody diarrhea (CWND) has an endoscopically normal colon, but colonic biopsies show unique inflammatory changes characteristic of lymphocytic or collagenous colitis. MC is a disorder of unknown etiology. Studies comparing the prevalence of the disease in developing countries as compared to developed countries may shed more light on the possibility of a post-infectious etiology. Most data on the incidence and prevalence of MC are from developed countries where it accounts for 4-13% of cases of CWND. There are only a few reports from developing countries. Two studies from Peru and Tunis, with high prevalence of infectious gastroenteritis, revealed MC in 40% and 29.3% of cases of CWND, respectively. The aim of this study was to investigate the prevalence of MC in patients presenting with CWND in Egypt. MATERIALS AND METHODS: A total of 44 patients with CWND of unexplained etiology who had undergone full colonoscopy with no macroscopic abnormalities between January 2000 and January 2010 were assessed retrospectively. RESULTS: The histological appearance of MC was identified in 22 (50%) patients. Twelve (55%) patients were male and 10 (45%) female. Mean age was 40 years (range: 20-65 years). Twenty (91%) of MC cases had lymphocytic colitis and 2 (9%) had collagenous colitis. CONCLUSIONS: The prevalence of MC in Egyptian patients with CWND is high when compared to that in developed countries. MC mainly affects young and middle-aged patients and it is more commonly of the lymphocytic type. PMID- 22064336 TI - In-hospital mortality among a cohort of cirrhotic patients admitted to a tertiary hospital. AB - BACKGROUND/AIM: To determine the mortality rate in a cohort of hospitalized patients with cirrhosis and examine their resuscitation status at admission. MATERIALS AND METHODS: A retrospective chart review was conducted of patients with cirrhosis who were admitted to a tertiary care hospital in Riyadh, Saudi Arabia, from January 1, 2009, to December 31, 2009. RESULTS: We reviewed 226 cirrhotic patients during the study period. The hospital mortality rate was 35%. A univariate analysis revealed that worse outcomes were seen in patients with advanced age or who had worse child-turcotte-pugh (CPT) scores, worse model for end-stage liver disease (MELD) scores, low albumin and high serum creatinine. Using a multivariate analysis, we found that advanced age (P=0.004) and high MELD (P=0.001) scores were independent risk factors for the mortality of cirrhotic patients. The end-of-life decision were made in 34% of cirrhotic patients, and the majority of deceased patients were "no resuscitation" status (90% vs. 4%, P<0.001). CONCLUSIONS: The relatively high mortality in cirrhotic patients admitted for care in a tertiary hospital, Saudi Arabia was comparable to that reported in the literature. Furthermore, end-of-life discussions should be addressed early in the hospitalization of cirrhotic patients. PMID- 22064337 TI - Enterocutaneous fistulae: etiology, treatment, and outcome - a study from South India. AB - BACKGROUND/AIM: Enterocutaneous fistula (ECF) is a difficult condition managed in the surgical wards and is associated with significant morbidity and mortality. Sepsis, malnutrition, and electrolyte abnormality is the classical triad of complications of ECF. Sepsis with malnutrition is the leading cause of death in cases of ECF. Although it is a common condition, no recent report in literature on the profile of patients with ECF has been documented from the southern part of India. MATERIALS AND METHODS: All consecutive patients who developed or presented with ECF during the study period were included in the study. The etiology, anatomic distribution, fistula output, clinical course, complications, predictive factors for spontaneous closure, and outcomes for patients with ECF were studied. RESULTS: A total of 41 patients were included in this prospective observational study, of which 34 were males and 7 were females. About 95% of ECF were postoperative. Ileum was found to be the most common site of ECF. Also, 49% of fistulas were high output and 51% were low output. Serum albumin levels correlated significantly with fistula healing and mortality. Surgical intervention was required in 41% of patients. CONCLUSION: Most of the ECF are encountered in the postoperative period. Serum albumin levels can predict fistula healing and mortality. Conservative management should be the first line of treatment. Mortality in patients with ECF continues to be significant and is commonly related to malnutrition and sepsis. PMID- 22064338 TI - High frequency of A2143G mutation in clarithromycin-resistant Helicobacter pylori isolates recovered from dyspeptic patients in Iran. AB - BACKGROUND/AIM: Resistance to clarithromycin in H. pylori isolates is accepted as a main cause of treatment failure in developing countries. We aimed to determine the prevalence of clarithromycin-resistant strains isolated from dyspeptic patients in northern Iran, furthermore we aimed to assess the relationship between clinical outcomes of infection with point mutations. MATERIALS AND METHODS: A total of 147 consecutive patients infected with H. pylori were included for determining the status of resistant H. pylori strains. With upper gastroscopy, three antral biopsies were taken from each patient, first section for rapid urea test, second for pathology and third section was used for bacterial culture in microbiologic lab. The antimicrobial susceptibility tests in this examination were agar dilution, in accordance with clinical and laboratory standards institue guidelines. Restriction fragment length polymorphism-PCR (RFLP PCR) method was applied to determine the frequency of point mutations in 23s rRNA gene. Statistical analysis was performed using SPSS software (15.0) (SPSS, Inc., Chicago, Ill). Chi-square and Fisher's exact tests were applied to our analysis. A P value less than 5% was considered as statistically significant. RESULTS: Our results showed that there was no point mutation in clarithromycin-susceptible strains of H. pylori. CONCLUSION: The important findings in our study indicate that A2143G is the most prevalent point mutation (30/32: 93.7%) attributed in clarithromycin resistance among the H. pylori strains. The current study concluded that clarithromycin could still be involved in the empirical treatment of H. pylori infection, although a high frequency of A2143G mutation may increase the concerns regarding treatment failure. PMID- 22064339 TI - Short-term outcome and quality of life of endoscopically placed gastric balloon and laparoscopic adjustable gastric band. AB - BACKGROUND/AIM: A prospective longitudinal study was conducted to describe short term outcome and quality of life (QOL) of endoscopically placed gastric balloon (EPGB) and laparoscopic adjustable gastric band (LAGB). MATERIALS AND METHODS: Forty seven consecutive patients with body mass index (BMI) of 42 to 72 kg/m2 were assigned to undergo EPGB (n=17) or LAGB (n=30) between May 2008 and May 2010. The main measured outcomes included weight loss, resolution or improvement of comorbidities, hospital stay, complications and QOL. RESULTS: Patients were followed up for a mean of 14 months. Hospital stay was shorter for EPGB patients (one versus two days, P<0.001). Early postoperative complications recorded in EPGB were minor including nausea and vomiting. No late complications were recorded in the EPGB group. One case of band slippage was reported in the LAGB group and fixed laparoscopically. Percent excess weight loss was less in EPGB compared to LAGB (26.2% versus 44.0%, P=0.004). Resolution or improvement of comorbidities was comparable in both groups. The globally impaired preoperative quality of life showed considerable improvement in both groups. CONCLUSION: EPGB is a safe and effective approach in short-term management of morbid obesity. Weight loss, resolution of comorbidities and improvement in QOL were comparable between both groups. PMID- 22064340 TI - Sexual dysfunction in males with hepatitis C virus: relevance to histopathologic changes and peginterferon treatment. AB - BACKGROUND/AIM: The frequency of sexual dysfunction (SD) is not well known in patients with chronic hepatitis C virus (HCV). In spite of the fact that histological benefits of peginterferon (Peg-IFN)/ribavirin therapy are well established, the effects on sexual health are less certain. To assess the prevalence of the SD and explore its relevance to histopathologic changes and Peg IFN treatment. MATERIALS AND METHODS: The study included 100 HCV males; all the patients completed questionnaires to assess their sexual function before and during the treatment. RESULTS: Before treatment, SD was reported only by 12 (19.4%) and 10 (29.4%) patients of early and advanced liver fibrosis, respectively. SD during HCV treatment (with Peg-IFN and ribavirin) for liver fibrosis was significant, as 24 (70.6%) out of 34 (100%) of HCV patients had advanced fibrosis but only 20 (32.3%) out of 62 (100%) patients had early fibrosis and were sexually affected (P = 0.01). SD before treatment was found in 22 (22%) patients; 16 (16%) were > 40 years old and 6 (6%) patients were <= 40 years old. SD showed highly significant (P = 0.001) difference prior to and during treatment. Pre treatment, 78 (78%) patients denied any SD and only 22 (22%) were sexually affected, while during treatment, the number of patients who were sexually affected rose to 44 (44%). The rest of the group [56 (56%)] did not report any sexual impairment. CONCLUSION: SD was noticed during Peg-IFN and ribavirin treatment in patients with advanced liver fibrosis. Age and advanced liver fibrosis were important factors in inducing SD. This is of key importance for clinical practice as it modifies the management of HCV patients. PMID- 22064341 TI - Coexistent ampullary squamous cell carcinoma with adenocarcinoma of the pancreatic duct. AB - Primary squamous cell carcinoma (SCC) of ampulla has seldom been reported. However, metastatic SCC to ampulla of Vater is well known. We report a case of primary SCC of ampulla of Vater coexistent with well-differentiated adenocarcinoma of the distal pancreatic duct. A 50-year-old female presented with evidence of obstructive jaundice. Endoscopic retrograde cholangio-pancreatography revealed bulging papilla with ulcero-infiltrative growth at the ampulla of Vater. An initial endoscopic biopsy of the ampullary mass showed a well-differentiated SCC. The patient underwent Whipple's operation. Thorough sampling of the dilated portion of the pancreatic duct showed presence of well-differentiated adenocarcinoma of the distal pancreatic duct. Immunohistochemical study with synaptophysin and chromogranin was done with negative result, ruling out neuroendocrine differentiation. Also, a detailed clinical, endoscopic and radiological examination was carried out, that excluded the presence of primary SCC elsewhere. PMID- 22064342 TI - Ulcerative colitis in infancy. AB - Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder of colon. Frequency of UC is gradually increasing over few years worldwide. Prevalence is 35 to 100/100,000 people in USA, 1% of them are infants. UC develops in a genetically predisposed individual with altered intestinal immune response. An eight-month-old girl presented with loose bloody stool, growth failure, and moderate pallor. The girl was diagnosed as a case of UC by colonoscopy and biopsy. Treatment was thereafter started with immunosuppressive drugs. After initial induction therapy with parenteral steroid and infliximab, the patient is now on remission with azathioprine and mesalamine. UC is rare in Bangladesh, especially in children, and it is rarer during infancy. Several conditions like infective colitis, allergic colitis, Meckel's diverticulitis, Crohn's disease, etc. may mimic the features of UC. So, if a child presents with recurrent bloody diarrhea, UC should be considered as differential diagnosis. PMID- 22064343 TI - Enterolith with enterocolic fistula: the diagnostic approach. AB - An enterolith is a mixed concretion formed in GIT, usually rare in humans. Primary enteroliths are formed in small bowel, typically within a diverticulum and secondary enteroliths in gallbladder. This case report highlights the presence of an enterocolic fistula; probably a postradiotherapy complication; and an enterolith without associated small bowel or colonic diverticuli. We have discussed the various diagnostic modalities used to reach a preoperative diagnosis of this rare condition. Imaging plays an important role in the detection and management of acquired gastrointestinal fistulas. The more routine use of cross-sectional imaging (especially computed tomography and magnetic resonance imaging) has altered the standard sequence of radiologic evaluation for possible fistulas, but fluoroscopic studies remain a valuable complement, especially for confirming and defining the anomalous communications. PMID- 22064344 TI - Unusual cause of rectal bleeding. Klippel-Trenaunay syndrome (KTS). PMID- 22064345 TI - Unusual late metastasis from gastric carcinoma. PMID- 22064346 TI - Successful application of ankaferd blood stopper in a patient with lower gastrointestinal bleeding. PMID- 22064347 TI - Helicobacter pylori and insulin resistance association: not just a myth, not yet a fact. PMID- 22064348 TI - AML1/ETO and POU4F1 synergy drives B-lymphoid gene expression typical of t(8;21) acute myeloid leukemia. PMID- 22064349 TI - Synergistic induction of p53 mediated apoptosis by valproic acid and nutlin-3 in acute myeloid leukemia. AB - Although TP53 mutations are rare in acute myeloid leukemia (AML), wild type p53 function is habitually annulled through overexpression of MDM2 or through various mechanisms including epigenetic silencing by histone deacetylases (HDACs). We hypothesized that co-inhibition of MDM2 and HDACs, with nutlin-3 and valproic acid (VPA) would additively inhibit growth in leukemic cells expressing wild type TP53 and induce p53-mediated apoptosis. In vitro studies with the combination demonstrated synergistic induction of apoptosis in AML cell lines and patient cells. Nutlin-3 and VPA co-treatment resulted in massive induction of p53, acetylated p53 and p53 target genes in comparison with either agent alone, followed by p53 dependent cell death with autophagic features. In primary AML cells, inhibition of proliferation by the combination therapy correlated with the CD34 expression level of AML blasts. To evaluate the combination in vivo, we developed an orthotopic, NOD/SCID IL2rgamma(null) xenograft model of MOLM-13 (AML FAB M5a; wild type TP53) expressing firefly luciferase. Survival analysis and bioluminescent imaging demonstrated the superior in vivo efficacy of the dual inhibition of MDM2 and HDAC in comparison with controls. Our results suggest the concomitant targeting of MDM2-p53 and HDAC inhibition, may be an effective therapeutic strategy for the treatment of AML. PMID- 22064350 TI - Glucocorticoid-induced TNFR-related protein (GITR) ligand modulates cytokine release and NK cell reactivity in chronic lymphocytic leukemia (CLL). AB - Natural killer (NK) cells play an important role in the immunosurveillance of hematopoietic malignancies. Their reactivity is influenced by activating and inhibitory signals mediated by tumor-expressed ligands for NK receptors. Many members of the tumor necrosis factor (TNF) family modulate differentiation, proliferation, activation and death of both tumor and immune effector cells. The TNF receptor family member glucocorticoid-induced TNFR-related protein (GITR) stimulates anti-tumor immunity in mice, but available data indicate that GITR may mediate different effects in mice and men and impairs the reactivity of human NK cells. Here, we comprehensively studied the expression and function of GITR ligand (GITRL) in leukemia. Among the different leukemia entities, pronounced expression of GITRL on leukemic cells was observed in chronic lymphocytic leukemia (CLL), and the GITR receptor was expressed at significantly higher levels on NK cells of CLL patients compared with healthy controls. Upon GITR GITRL interaction, signaling via GITRL into the leukemia cells induced the release of interleukin (IL)-6, IL-8 and TNF, which act as growth and survival factors for CLL cells. In addition, GITRL impaired both direct and Rituximab induced degranulation, cytotoxicity and interferon-gamma production of NK cells, which could be restored by GITR blocking antibodies. Thus, GITRL may contribute to disease pathophysiology and resistance to direct and Rituximab-induced NK reactivity in CLL. PMID- 22064351 TI - MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-activated MCL-1 induction and modulation of MCL-1/BIM complex. AB - Recently, strategies for acute myeloid leukemia (AML) therapy have been developed that target anti-apoptotic BCL2 family members using BH3-mimetic drugs such as ABT-737. Though effective against BCL2 and BCL-X(L), ABT-737 poorly inhibits MCL 1. Here we report that, unexpectedly, ABT-737 induces activation of the extracellular receptor activated kinase and induction of MCL-1 in AML cells. MEK inhibitors such as PD0325901 and CI-1040 have been used successfully to suppress MCL-1. We report that PD0325901 blocked ABT-737-induced MCL-1 expression, and when combined with ABT-737 resulted in potent synergistic killing of AML-derived cell lines, primary AML blast and CD34+38-123+ progenitor/stem cells. Finally, we tested the combination of ABT-737 and CI-1040 in a murine xenograft model using MOLM-13 human leukemia cells.Whereas control mice and CI-1040-treated mice exhibited progressive leukemia growth, ABT-737, and to a significantly greater extent, ABT-737+CI-1040 exerted major anti-leukemia activity. Collectively, results demonstrated unexpected anti-apoptotic interaction between the BCL2 family-targeted BH3-mimetic ABT-737 and mitogen-activated protein kinase signaling in AML cells: the BH3 mimetic is not only restrained in its activity by MCL-1, but also induces its expression. However, concomitant inhibition by BH3 mimetics and MEK inhibitors could abrogate this effect and may be developed into a novel and effective therapeutic strategy for patients with AML. PMID- 22064352 TI - CALM/AF10-positive leukemias show upregulation of genes involved in chromatin assembly and DNA repair processes and of genes adjacent to the breakpoint at 10p12. AB - The t(10;11)(p12;q14) is a recurring chromosomal translocation that gives rise to the CALM/AF10 fusion gene, which is found in acute myeloid leukemia, acute lymphoblastic leukemia and malignant lymphoma. We analyzed the fusion transcripts in 20 new cases of CALM/AF10-positive leukemias, and compared the gene expression profile of 10 of these to 125 patients with other types of leukemia and 10 normal bone marrow samples. Based on gene set enrichment analyses, the CALM/AF10 positive samples showed significant upregulation of genes involved in chromatin assembly and maintenance and DNA repair process, and downregulation of angiogenesis and cell communication genes. Interestingly, we observed a striking upregulation of four genes located immediately centromeric to the break point of the t(10;11)(p12;q14) on 10p12 (COMMD3 (COMM domain containing 3), BMI1 (B lymphoma Mo-MLV insertion region 1 homolog), DNAJC1 (DnaJ (Hsp40) homolog subfamily C member 1) and SPAG6 (sperm associated antigen 6)). We also conducted semiquantitative reverse transcriptase-PCR analysis on leukemic blasts from a murine CALM/AF10 transplantation model that does not have the translocation. Commd3, Bmi1 and Dnajc1, but not Spag6 were upregulated in these samples. These results strongly indicate that the differential regulation of these three genes is not due to the break point effect but as a consequence of the CALM/AF10 fusion gene expression, though the mechanism of regulation is not well understood. PMID- 22064353 TI - SF3B1 mutations in primary myelofibrosis: clinical, histopathology and genetic correlates among 155 patients. PMID- 22064354 TI - Oral high-dose glucocorticoids and ofatumumab in fludarabine-resistant chronic lymphocytic leukemia. PMID- 22064355 TI - SF3B1 mutations in myelodysplastic syndromes: clinical associations and prognostic implications. PMID- 22064356 TI - 4-(3,5-Dimethyl-1H-pyrazol-1-yl)benzene-sulfonamide. AB - The two aromatic rings of the title compound, C(11)H(13)N(3)O(2)S, are inclined at an angle of 47.81 (4) degrees . The N atom of the amino unit is pyramidally coordinated; one H atom inter-acts with the sulfamyl O atom of an adjacent mol ecule, forming a centrosymmetric hydrogen-bonded dimer. The dimers are linked by N-H?N hydrogen bonds, generating a three-dimensional network. PMID- 22064357 TI - 4-(2-Azaniumyl-eth-yl)piperazin-1-ium bis(perchlorate). AB - In the title compound, C(6)H(17)N(3) (2+).2ClO(4) (-), the piperazine ring adopts a chair conformation with the ethyl-ammonium fragment occupying an equatorial position. In the crystal, the dications and perchlorate anions are linked through N-H?O hydrogen bonding and weak C-H?O hydrogen bonding into a three-dimensional supra-molecular network. PMID- 22064359 TI - Muscle and blood redox status after exercise training in severe COPD patients. AB - Beneficial effects of exercise training in patients with chronic obstructive pulmonary disease (COPD) are acknowledged. However, high-intensity exercise may enhance muscle oxidative stress in severe COPD patients. We hypothesized that high-intensity exercise training of long duration does not deteriorate muscle redox status. In the vastus lateralis and blood of 18 severe COPD patients and 12 controls, before and after an 8-week training program, protein oxidation and nitration, antioxidant systems, and inflammatory cytokines were examined. At baseline, COPD patients showed greater muscle oxidative stress and superoxide dismutase activity and circulating inflammatory cytokines than controls. Among COPD patients, muscle and blood protein carbonylation levels were correlated. Both groups showed training-induced increase in VO(2) peak and decreased blood lactate levels. After training, among the COPD patients, blood protein nitration levels were significantly reduced and muscle protein oxidation and nitration levels did not cause impairment. Muscle and blood levels of inflammatory cytokines were not modified by training in either patients or controls. We conclude that in severe COPD patients, high-intensity exercise training of long duration improves exercise capacity while preventing the enhancement of systemic and muscle oxidative stress. In addition, in these patients, resting protein oxidation levels correlate between skeletal muscle and blood compartments. PMID- 22064360 TI - 3',4'-didemethylnobiletin induces phase II detoxification gene expression and modulates PI3K/Akt signaling in PC12 cells. AB - Oxidative stress is considered a major cause of neurodegenerative disorders. In this work, we investigated the cytoprotective effects and mechanisms of the citrus flavonoid nobiletin (NOB) and its metabolite, 3',4'-didemethylnobiletin (3',4'-dihydroxy-5,6,7,8-tetramethoxyflavone; DTF), in PC12 cells. Both NOB and DTF exhibited strong potency in attenuating serum withdrawal- and H(2)O(2)-caused cell death and increased intracellular GSH level via upregulation of both catalytic and modifier subunits of glutamate-cysteine ligase (GCL). However, only DTF suppressed intracellular ROS accumulation in H(2)O(2)-treated cells, induced heme oxygenase-1 (HO-1) expression, and enhanced nuclear factor E2-related factor 2 (Nrf2) binding to the ARE. Nevertheless, DTF-mediated HO-1 upregulation was independent of Nrf2 activation because knockdown of Nrf2 expression by siRNA did not affect its expression. DTF suppressed NF-kappaB activation, and addition of NF-kappaB inhibitor, pyrrolidine dithiocarbamate or Bay 11-7082, synergistically enhanced DTF-mediated HO-1 expression, indicating that HO-1 induction is associated with NF-kappaB suppression. NOB and DTF also activated the ERK, JNK, and Akt pathways in PC12 cells that had undergone serum starvation. Addition of pharmacological kinase inhibitors, U0126, SP600125, and LY294002, caused cytotoxicity and the last significantly attenuated NOB- and DTF-mediated antiapoptotic actions, indicating the involvement of PI3K/Akt signaling in their cytoprotective effects. In conclusion, HO-1 and GCL upregulation and intrinsic ROS-scavenging activity may contribute to DTF-mediated cytoprotection. Furthermore, modulation of PI3K/Akt signaling is involved in channeling the DTF stimulus for cell survival against oxidative insults. PMID- 22064361 TI - Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. AB - The worldwide rising prevalence of obesity and insulin resistance is associated with a parallel increase in nonalcoholic fatty liver disease (NAFLD). NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to increased inflow of free fatty acids and/or de novo lipogenesis caused by various drugs and multiple defects in energy metabolism. Accumulation of lipids in the hepatocyte impairs the oxidative capacity of the mitochondria, increasing the reduced state of the electron transport chain (ETC) complexes and stimulating peroxisomal and microsomal pathways of fat oxidation. The consequent increased generation of reactive oxygen species (ROS) and reactive aldehydic derivatives causes oxidative stress and cell death, via ATP, NAD, and glutathione depletion and DNA, lipid, and protein damage. Oxidative stress also triggers production of inflammatory cytokines, causing inflammation and a fibrogenic response. This ultimately results in the development of nonalcoholic steatohepatitis (NASH), which can result in end-stage liver disease. The current therapeutic strategies for NASH treatment are mostly directed toward correction of the risk factors. Stimulation of mitochondrial function may also prevent NASH development, protecting the cell against the increased flux of reduced substrates to the ETC and ROS generation. PMID- 22064362 TI - Reactive oxygen species are produced at low glucose and contribute to the activation of AMPK in insulin-secreting cells. AB - Excess reactive oxygen species (ROS) production is thought to play a key role in the loss of pancreatic beta-cell number and/or function, in response to high glucose and/or fatty acids. However, contradictory findings have been reported showing that in pancreatic beta cells or insulin-secreting cell lines, ROS are produced under conditions of either high or low glucose. Superoxide production was measured in attached INS1E cells as a function of glucose concentration, by following in real time the oxidation of dihydroethidine. Minimal values of superoxide production were measured at glucose concentrations of 5-20 mM, whereas superoxide generation was maximal at 0-1 mM glucose. Superoxide generation started rapidly (15-30 min) after exposure to low glucose and was suppressed by its addition within minutes. Superoxide was totally suppressed by rotenone, but not myxothiazol, suggesting a role for complex I in this process. Indirect evidence for mitochondrial ROS generation was also provided by a decrease in aconitase activity. Activation of AMPK, a cellular metabolic sensor, and its downstream target ACC by low glucose concentration was largely inhibited by addition of MnTBAP, a MnSOD and catalase mimetic that also totally suppressed superoxide production. Taken together, the data show that low glucose activates AMPK in a superoxide-dependent, AMP-independent way. PMID- 22064364 TI - Small molecule inhibitors of mammalian thioredoxin reductase. AB - Mammalian thioredoxin reductases (TrxRs) are a family of NADPH-dependent flavoproteins with a penultimate selenocysteine residue at the carboxy-terminus. Besides their native substrate thioredoxins (Trx), the enzymes show a broad substrate specificity, at least partially, because of the C-terminal redox-active site that is easily accessible in the reduced form. TrxRs are ubiquitous in all kinds of cells and have a critical role in regulating intracellular redox signaling. In recent years, a wealth of evidence has revealed that overactivation/dysfunction of TrxRs is closely related to various diseases, especially in tumor development, and thus the past decades have witnessed an expanding interest in finding TrxRs inhibitors, which might be promising agents for cancer chemotherapy. Herein we reviewed the small molecule inhibitors of mammalian TrxRs, with an emphasis on those that have potential anticancer activity. This review includes the nonpatent references up to 2010 that deal with mammalian TrxR inhibitors. PMID- 22064363 TI - Peroxidase-mediated dealkylation of tamoxifen, detected by electrospray ionization-mass spectrometry, and activation to form DNA adducts. AB - Tamoxifen (TAM) is extensively used for the treatment and prevention of breast cancer. Associated with TAM treatment is a two- to eightfold increase in risk of endometrial cancer. To understand the mechanisms associated with this increased risk several pathways for TAM metabolism and DNA adduct formation have been studied. The purpose of this study was to investigate the role of peroxidase enzymes in the metabolism of TAM and its activation to form DNA adducts. Using advanced tandem mass spectrometry we have investigated the peroxidase-mediated metabolism of TAM. Incubation of TAM with horseradish peroxidase (HRP) and H(2)O(2) produced multiple metabolites. Electrospray ionization-MS/MS analysis of the metabolites demonstrated a peak at 301.3m/z with daughter ions at 183.0, 166.9, 128.9, and 120.9m/z, which identified the metabolite as metabolite E (ME). The levels of ME were significantly inhibited by the addition of ascorbic acid to the incubation mixture. Co-incubation of either TAM or ME and DNA with HRP and H(2)O(2) produced three DNA adducts with a RAL of 1.97+/-0.01*10(-7) and 8.45+/ 2.7*10(-7). Oxidation of ME with MnO(2) produced metabolite E quinone methide (MEQM). Furthermore, incubation of either TAM or ME with HRP and H(2)O(2) resulted in formation of MEQM. Reaction of calf thymus DNA with MEQM produced three DNA adducts with a RAL of 9.8+/-1.0*10(-7). Rechromatography analyses indicated that DNA adducts 1, 2, and 3 formed in the HRP activation of either TAM or ME were the same as those formed by the chemical reaction of DNA with MEQM. The results of these studies demonstrate that peroxidase enzymes can both metabolize TAM to form the primary metabolite ME and activate ME to a quinone methide intermediate, which reacts with DNA to form adducts. It is possible that peroxidase enzymes or peroxidase-like activity in endometrium could contribute to the formation of DNA damage and genotoxic effects in endometrium after TAM administration. PMID- 22064365 TI - Quantification of hydroxyl radical-derived oxidation products in peptides containing glycine, alanine, valine, and proline. AB - Proteins are a major target for oxidation due to their abundance and high reactivity. Despite extensive investigation over many years, only limited quantitative data exist on the contributions of different pathways to the oxidation of peptides and proteins. This study was designed to obtain quantitative data on the nature and yields of oxidation products (alcohols, carbonyls, hydroperoxides, fragment species) formed by a prototypic oxidant system (HO(*)/O(2)) on small peptides of limited, but known, amino acid composition. Peptides composed of Gly, Ala, Val, and Pro were examined with particular emphasis on the peptide Val-Gly-Val-Ala-Pro-Gly, a repeat motif in elastin with chemotactic activity and metalloproteinase regulation properties. The data obtained indicate that hydroperoxide formation occurs nonrandomly (Pro > Val > Ala > Gly) with this inversely related to carbonyl yields (both peptide bound and released). Multiple alcohols are generated at both side-chain and backbone sites. Backbone fragmentation has been characterized at multiple positions, with sites adjacent to Pro residues being of major importance. Summation of the product concentrations provides clear evidence for the occurrence of chain reactions in peptides exposed to HO(*)/O(2), with the overall product yields exceeding that of the initial HO(*) generated. PMID- 22064366 TI - 4,4'-Bipyridine-1,1'-diium 2,3,5,6-tetra-bromo-terephthalate dihydrate. AB - The title compound, C(10)H(10)N(2) (2+).C(8)Br(4)O(4) (2-).2H(2)O, consists of a tetra-bromo-terephthalate dianion, a 4,4'-bipyridinium dication and two solvent water mol-ecules. Crystallographic inversion centers are situated at the center of the aromatic ring of the dianion as well as at the midpoint of the carbon carbon bond connecting the pyridine rings in the dication. In the crystal, inter molecular N-H?O hydrogen-bonding inter-actions between tetra-bromo-terephthalate dianions and protonated 4,4'-bipyridinium dications result in the formation of a chain-like structure. Further O-H?O hydrogen bonds between carboxyl-ate O atoms and water mol-ecules lead to the formation of a two-dimensional network in the crystal structure. PMID- 22064367 TI - Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries. AB - Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority <15.4%) of the individual target inhibitors of the same target pair and 0.58-7.1% of the other 6 targets outside the target pair. COMBI-SVMs showed low dual inhibitor false hit rates (0.006-0.056%, 0.042-0.21%, 0.2-4%) in screening 17 million PubChem compounds, 168,000 MDDR compounds, and 7-8181 MDDR compounds similar to the dual inhibitors. Compared with similarity searching, k-NN and PNN methods, COMBI-SVM produced comparable dual inhibitor yields, similar target selectivity, and lower false hit rate in screening 168,000 MDDR compounds. The annotated classes of many COMBI-SVMs identified MDDR virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. PMID- 22064368 TI - Ba(11)La(4)Br(34): a new barium lanthanum bromide. AB - The structure of the title compound, barium lanthanum bromide (11/4/34), can be derived from the fluorite structure. The asymmetric unit contains two Ba sites (one with site symmetry 4/m..), one La site (site symmetry 4..), one mixed occupied Ba and La site (ratio 1:1, site symmetry m..) and six Br sites (one with site symmetry ?=4.., one with 2.., one with m.., the latter being disordered over two positions with a 0.86:0.14 ratio). The fundamental building units of the structure are edge-sharing polyhedral clusters made up of Ba and La bromide clusters inter-connected to BaBr(8) square prisms and BaBr(10) groups. PMID- 22064369 TI - Analysis of the effect of perioperative magnesium sulphate on minimal alveolar concentration of desflurane using bispectral index monitoring. AB - BACKGROUND: In this study we aimed to analyze the effect of perioperative magnesium sulphate (MgSO(4)) on minimal alveolar concentration (MAC) of desflurane using bispectral index (BIS) monitoring. PATIENTS AND METHODS: Sixty patients undergoing abdominal surgery under general anesthesia were randomized into two groups: Mg - receiving perioperative MgSO(4) supplementation and C - control. Anesthesia was titrated to maintain the BIS value between 45-55. RESULTS: MAC values, tachycardia and hypertension during intubation was found to be lower in group Mg compared to group C (p<0.001). Time to extubation, verbal cooperation and eye opening was longer in patients receiving infusion of MgSO(4) (p<0.001). CONCLUSION: We concluded that perioperative MgSO(4) infusion may be used as an adjunct as it decreases MAC of desflurane and suppresses the hemodynamic response to intubation. PMID- 22064370 TI - A study of prevalence and pattern of hyperactive syndrome in primary school children. AB - Prevalence of hyperactive syndrome in 2160 primary school children between the age of 6-12 years was found to be 4.67%. The ratio of male, female distribution of hyperactive syndrome was found to be 4.74: 1. It was significantly associated with type of school (only in girls), age (only in boys) and occupation of father (only in boys). Hyperkinetic behaviour of children was not significantly associated with income of parents. Family structure and dynamics of hyperactive children studied did not reveal gross pathology. Some of the hyperactive children were found to be impulsive in their cognitive style and others experienced difficulties in visuo-spatial perception and visuo-motor coordination. PMID- 22064371 TI - catena-Poly[[diaqua-bis-{MU(2)-3,5-bis-[(pyridin-4-yl)methyl-amino] benzoato}nickel] monohydrate]. AB - In the title coordination polymer, {[Ni(C(19)H(17)N(4)O(2))(2)(H(2)O)(2)].H(2)O}(n), the Ni(2+) cation is located on an inversion center and coordinated by two carboxyl-ate O atoms from two different 3,5-bis-(pyridin-4-yl-methyl-amino)-benzoate anions, two O atoms from two coordinated water mol-ecules and two N atoms from two different 3,5-bis (pyridin-4-yl-methyl-amino)-benzoate anions, displaying a slightly distorted NiN(2)O(4) octa-hedral geometry. Each 3,5-bis-(pyridin-4-yl-methyl-amino) benzoate anion acts as a MU(2)-bridge, linking different nickel ions into a chain along [010]. In the crystal, adjacent chains are further linked through N-H?O, O H?O, O-H?N and C-H?O hydrogen bonds into a three-dimensional network. The coordinated water mol-ecules and a disordered water mol-ecule of hydration with 0.50 site occupancy play an important role in the formation of these hydrogen bonding inter-actions. PMID- 22064372 TI - Intra and extra erythrocyte lithium ion concentration ratios in manic patients. AB - In a study RBC-Plasma lithium ratios in manic patients treated with lithium we found that lithium responders had higher lithium ratios than lithium non responders. There was, however, no cut off value which could differentiate lithium responders from non-responders. PMID- 22064373 TI - Thromboembolic events are associated with prolonged clot lysis time in patients with permanent atrial fibrillation. AB - INTRODUCTION: Atrial fibrillation (AF) is associated with a prothrombotic state. OBJECTIVES: We evaluated associations of previous thromboembolic events with fibrinolytic parameters in patients with AF. PATIENTS AND METHODS: We studied 62 consecutive patients with permanent AF (27 men, 35 women, aged 46-89 years [median, 78 years]). Patients receiving warfarin or acenocoumarol on a long-term basis were eligible. We determined plasma fibrin clot lysis time (CLT), plasminogen activator inhibitor-1 (PAI-1) antigen, thrombin-activatable fibrinolysis inhibitor (TAFI) activity and antigen, plasminogen, alpha2 antiplasmin (alpha2AP), and soluble thrombomodulin (sTM). RESULTS: There were 19 subjects (30.6%) with a history of thrombotic events (stroke in 11, myocardial infarction in 8, and pulmonary embolism in 3 patients). They had longer CLT (P = 0.0035 for patients with previous stroke and P = 0.001 for patients with any previous thrombotic event), together with higher PAI-1 (P = 0.025 and P = 0.016, respectively), TAFI activity (P = 0.002 and P = 0.011, respectively), sTM (P = 0.0023 and P = 0.012, respectively), and alpha2AP (P = 0.007 and P = 0.0006, respectively) than the remaining subjects. AF patients with previous stroke had also higher TAFI antigen than the remainder (P = 0.04). CLT (P = 0.024), PAI-1 (P = 0.022), TAFI activity (P = 0.048), and sTM (P = 0.032, all P for trend) increased with higher CHA2DS2-VASc scores. CLT was not associated with time from thrombotic event to enrollment. Patients taking oral anticoagulants (n = 46) had only slightly higher sTM levels (3.6 [2.9-6.3] vs. 2.9 [2.2-4.1] ng/ml, P = 0.049) than the remaining subjects. CONCLUSIONS: Stroke or other thromboembolic event in AF patients is associated with impaired lysability of fibrin clots combined with elevated PAI-1, TAFI, sTM, and alpha2AP. PMID- 22064374 TI - S-Adenosylhomocysteine enhances DNA damage through increased beta-amyloid formation and inhibition of the DNA-repair enzyme OGG1b in microglial BV-2 cells. AB - S-Adenosylhomocysteine (SAH) is a risk factor for neurodegenerative diseases such as Alzheimer's disease, for which beta-Amyliod (Abeta) formation is a major risk factor. We recently showed that SAH increases Abeta formation in mouse microglial BV2 cells. Here, we show that incubation of BV2 cells with SAH (0-500nM) for 6 24h sequentially increased Abeta formation, ROS and DNA damage measured as 8-oxo deoxyguanosine (8-oxo-dG) levels. Pre-incubation of BV2 cells with 20MUM beta secretase inhibitor IV for 30min followed by incubation with SAH (500nM) markedly decreased Abeta formation and 8-oxo-dG levels. Treatment with SAH for 24h concentration-dependently inhibited DNA methyltransferase (DNMT1) activity and inhibited DNMT1 binding to Sp1 site of 8-oxoG-DNA glycosylases I (OGG1) promoter and OGG1 protein and mRNA expression at 24h; the latter effect was attributed to hypomethylation of the OGG1 gene promoter, because pre-incubation of cells with betaine (1.0mM for 30 min) markedly prevented the inhibition of OGG1 protein expression induced by SAH. Overall, we demonstrate that SAH increases DNA damage in BV-2 cells possible by increased Abeta formation leading to increased formation of ROS. Furthermore, the DNA damage is enhanced by SAH through inhibition of DNMT1 activity and hypomethylation of OGG1 gene promoter. PMID- 22064375 TI - Dibromidooxido[(Z)-N'-(propan-2-yl-idene)benzohydrazidato](triphenyl phosphane)rhenium(V). AB - The asymmetric unit of the title neutral rhenium(V) coordination compound, [ReBr(2)(C(10)H(11)N(2)O)O(C(18)H(15)P)], contains two mol-ecules. In each of the two molecules the metal atom is octa-hedrally coordinated, the bromido ligands being cis-orientated. The chelate ligand is present in its imine-tautomeric form. In the crystal, C-H?Br contacts connect the mol-ecules into chains along [101]. The shortest inter-centroid distance between two aromatic rings was found to be 3.906 (2) A. PMID- 22064376 TI - Efficacy and safety of antidepressant drug treatment in children and adolescents. AB - Depression and anxiety are common disorders in youth that can have profound influences on functioning and even mortality. In the late 1990s, large controlled trials began demonstrating the efficacy of selective serotonin reuptake inhibitors for these conditions in the pediatric population. By 2003, regulatory agencies began warning the public of unrecognized risk and misrepresented benefit. The current review article summarizes a series of published and unpublished efficacy and safety data regarding antidepressant use in children and adolescents. The resulting complex synthesis suggests that these medications may offer mild-to-moderate benefit, with notable exceptions depending on medication and indication, but they may also heighten the risk for suicidal ideation and parasuicidal behavior. However, reviewed epidemiological data does not demonstrate a relationship between newer antidepressant prescription and completed suicide in large populations of youth. In conclusion, this breadth of mixed research data is applied to clinical decision making. PMID- 22064377 TI - African ancestry protects against Alzheimer's disease-related neuropathology. AB - Previous studies in dementia epidemiology have reported higher Alzheimer's disease rates in African-Americans when compared with White Americans. To determine whether genetically determined African ancestry is associated with neuropathological changes commonly associated with dementia, we analyzed a population-based brain bank in the highly admixed city of Sao Paulo, Brazil. African ancestry was estimated through the use of previously described ancestry informative markers. Risk of presence of neuritic plaques, neurofibrillary tangles, small vessel disease, brain infarcts and Lewy bodies in subjects with significant African ancestry versus those without was determined. Results were adjusted for multiple environmental risk factors, demographic variables and apolipoprotein E genotype. African ancestry was inversely correlated with neuritic plaques (P=0.03). Subjects with significant African ancestry (n=112, 55.4%) showed lower prevalence of neuritic plaques in the univariate analysis (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.55-0.95, P=0.01) and when adjusted for age, sex, APOE genotype and environmental risk factors (OR 0.43, 95% CI 0.21-0.89, P=0.02). There were no significant differences for the presence of other neuropathological alterations. We show for the first time, using genetically determined ancestry, that African ancestry may be highly protective of Alzheimer's disease neuropathology, functioning through either genetic variants or unknown environmental factors. Epidemiological studies correlating African-American race/ethnicity with increased Alzheimer's disease rates should not be interpreted as surrogates of genetic ancestry or considered to represent African-derived populations from the developing nations such as Brazil. PMID- 22064379 TI - Conversion of a murine monoclonal antibody A13 targeting epidermal growth factor receptor to a human monoclonal antibody by guided selection. AB - Epidermal growth factor receptor (EGFR) is an attractive target for tumor therapy because it is overexpressed in the majority of solid tumors and the increase in receptor expression levels has been linked with a poor clinical prognosis. Also it is well established that blocking the interaction of EGFR and the growth factors could lead to the arrest of tumor growth and possibly result in tumor cell death. A13 is a murine monoclonal antibody (mAb) that specifically binds to various sets of EGFR-expressing tumor cells and inhibits EGF-induced EGFR phosphorylation. We isolated human immunoglobulin genes by guided selection based on the mAb A13. Four different human single chain Fvs (scFvs) were isolated from from hybrid scFv libraries containing a human VH repertoire with the VL of mAb A13 and a human VL repertoire with the VH of mAb A13. All the 4 scFvs bound to EGFR-expressing A431 cells. One scFv (SC414) with the highest affinity was converted to IgG1 (ER414). The ER414 exhibited ~17 fold lower affinity compared to the A13 mAb. In addition the ER414 inhibited an EGF-induced tyrosine phosphorylation of EGFR with much lower efficacy compared to the A13 mAb and Cetuximab (Merck KgaA, Germany). We identified that the epitope of A13 mAb is retained in ER414. This approach will provide an efficient way of converting a murine mAb to a human mAb. PMID- 22064380 TI - Reverse transcriptase real-time PCR for detection and quantification of viable Campylobacter jejuni directly from poultry faecal samples. AB - Campylobacter spp. is the most common cause of bacterial diarrhoea in humans worldwide. Therefore, rapid and reliable methods for detection and quantification of this pathogen are required. In this study, we have developed a reverse transcription quantitative real-time PCR (RT-qPCR) for detection and quantification of viable Campylobacter jejuni directly from chicken faecal samples. The results of this method and a DNA-based quantitative real-time PCR (qPCR) method were compared with those of a bacterial culture method. Using bacterial culture and RT-qPCR methods, viable C. jejuni cells could be detected for up to 5 days in both the C. jejuni spiked and the naturally contaminated faecal samples. We found that no RT-qPCR signals were obtained when viable C. jejuni cells could not be counted by the culture method. In contrast, using a DNA based qPCR method, dead or non-viable Campylobacter cells were detected, and all tested samples were positive, even after 20 days of storage. The developed method for detection and quantification of viable C. jejuni cells directly from chicken faecal samples can be used for further research on the survival of Campylobacter in the environment. PMID- 22064381 TI - Di-MU-chlorido-bis-{[1,2-bis-(pyridin-2-ylmeth-oxy)benzene kappaN,O,O',N']chloridocadmium}. AB - In centrosymmetric dinuclear title compound, [Cd(2)Cl(4)(C(18)H(16)N(2)O(2))(2)], the Cd(II) atom is seven-coordinated in a penta-gonal-bipyramidal environment defined by two N atoms and two O atoms from one ligand and three Cl(-) anions, two of which are bridging. A pi-pi inter-action between adjacent pyridine rings [centroid-centroid distance = 3.773 (1) A] further stablizes the dimer. PMID- 22064382 TI - Bis(1,4,7-trithia-cyclo-nona-ne)nickel(II) bis-(tetra-fluorido-borate) nitro methane disolvate. AB - The homoleptic thio-ether title complex, [Ni(C(6)H(12)S(3))(2)](BF(4))(2).2CH(3)NO(2), shows the expeced hexa-kis-(thio ether) octa-hedral environment around the Ni(II) atom. It crystallized as two crystallographically independent complex cations, [Ni(9S3)(2)](2+) (9S3 = 1,4,7 trithia-cyclo-nona-ne), within the unit cell where each Ni(II) lies on an inversion center. In addition to the complex cations, there are two crystallographically independent BF(4) (-) anions present to balance the charge, and each shows disorder along a pseudo-C(3) axis with ratios of 0.53 (2):0.47 (2) and 0.55 (2):0.45 (2). Two nitro-methane solvent mol-ecules per complex cation are also present in the unit cell. PMID- 22064383 TI - Heptamagnesium bis-(phosphate) tetra-kis-(hydrogen phosphate) with strong hydrogen bonds: Mg(7)(PO(4))(2)(HPO(4))(4). AB - The title compound, Mg(7)(PO(4))(2)(HPO(4))(4), was synthesized by the hydro thermal method. The structure is based on a framework of edge- and corner-sharing MgO(6) and MgO(4)(OH)(2) octa-hedra, an MgO(5) polyhedron, PO(4) and PO(3)(OH) tetra-hedra. All atoms are in general positions except for one Mg atom, which is located on a crystallographic inversion centre. The OH groups, bridging Mg-(OH) P, are involved in strong hydrogen bonds. Compounds with the general formula M(7)(PO(4))(2)(HPO(4))(4) (M = Mg, Mn, Fe and Co) are all isostructural with their homologue arsenate Mg(7)(AsO(4))(2)(HAsO(4))(4). PMID- 22064384 TI - Flash photolysis of caged compounds in the cilia of olfactory sensory neurons. AB - Photolysis of caged compounds allows the production of rapid and localized increases in the concentration of various physiologically active compounds. Caged compounds are molecules made physiologically inactive by a chemical cage that can be broken by a flash of ultraviolet light. Here, we show how to obtain patch clamp recordings combined with photolysis of caged compounds for the study of olfactory transduction in dissociated mouse olfactory sensory neurons. The process of olfactory transduction (Figure 1) takes place in the cilia of olfactory sensory neurons, where odorant binding to receptors leads to the increase of cAMP that opens cyclic nucleotide-gated (CNG) channels. Ca entry through CNG channels activates Ca-activated Cl channels. We show how to dissociate neurons from the mouse olfactory epithelium and how to activate CNG channels or Ca-activated Cl channels by photolysis of caged cAMP or caged Ca. We use a flash lamp to apply ultraviolet flashes to the ciliary region to uncage cAMP or Ca while patch-clamp recordings are taken to measure the current in the whole-cell voltage-clamp configuration. PMID- 22064385 TI - Interleukin 1beta regulates progesterone metabolism in human cervical fibroblasts. AB - Progesterone plays a critical role in regulating cervical structure necessary for pregnancy maintenance. Preterm labor and early cervical ripening are often associated with localized infection. We hypothesized that proinflammatory cytokines enhance progesterone metabolism in human cervical fibroblasts (HCFs) in vitro, through the regulation of the expression of 20alpha-hydroxysteroid dehydrogenases (aldo-keto reductase [AKR]1C1, AKR1C2, or AKR1C3), 5alpha reductase type 1 (5alpha-RDT1), and/or 17beta-hydroxysteroid dehyrogenases (17beta-HSD) type 1 and 2. The expression of both progesterone receptor (PR) and estrogen receptor alpha (ERalpha) was also studied. Human cervical fibroblasts were found to express AKR1C1, C2, and C3, with AKR1C1 exhibiting the greatest expression. These cells also expressed 5alpha-RDT1 and 17beta-HSD1 and 2, albeit to a lesser level compared to the aldo-keto reductases. The fibroblasts also expressed both PR and ERalpha. Interleukin 1beta (IL-1beta) significantly increased the expression of AKR1C1 and C2 but not C3 but did not alter 5alpha RDT1 nor 17beta-HSD1 or 2 expression. Interleukin 1beta treatment significantly increased progesterone metabolism by these cells. Use of specific inhibitors for aldo-keto reductases or 5alpha reductases confirmed that the increased progesterone metabolism was a consequence of the increased expression and/or activity of AKR1C1/2. Our results indicate that a major proinflammatory cytokine, IL-1beta, can facilitate local progesterone metabolism in a cell type critical for maintaining cervical structure via regulating expression of AKR1C1 and 2. PMID- 22064386 TI - Role of label-retaining cells in estrogen-induced endometrial regeneration. AB - Candidate stem/progenitor cells have been identified in mouse endometrium as label-retaining cells (LRCs). The role of endometrial stem/progenitor cells in initiating estrogen-stimulated endometrial growth in prepubertal and cycling mice was investigated following a single 17beta-estradiol (E2) injection in bromodeoxyuridine (BrdU)-labeled and -chased (LRC), ovariectomised mice. Proliferating (BrdU(+)/Ki-67(+)) and mitotic (BrdU(+)/PH3(+)) epithelial LRCs were first detected in prepubertal mice 8 hours following E2 treatment, initiating the proliferative response. In contrast, all epithelial LRCs and 16% of epithelial cells in cycling mice proliferated within 2 hours. In cycling mice, 12% of stromal LRCs initiated a proliferative response 8 hours after E2. Proliferating epithelial LRCs and most stromal LRCs (85%) lacked estrogen receptor-alpha (ESR1). These findings suggest that endometrial epithelial LRCs function as stem/progenitor cells by receiving proliferative signals from neighboring ESR1(+) niche cells to initiate the growth of the epithelium during development, while mature epithelial cells may undergo self-replication in cycling endometrium. PMID- 22064387 TI - Cyclic changes in the expression of p57(kip2) in human endometrium and its regulation by steroid hormones in endometrial stromal cells in vitro. AB - We investigated the expressions of p57(kip2) and p27(kip) and its regulation by steroids in the normal and abnormal human endometrium. Endometrial p27(kip1) and p57(kip2) messenger RNA (mRNA) were markedly increased in the secretory phase. P57(kip2) protein was absent in proliferative phase but appeared in glandular epithelium together with early- to mid-secretory phase stromal cells. During the late secretory phase, strong P57(kip2) protein immunoreactivity was found in the stromal cells. In both endometrial hyperplasia and cancer, the expression of P57(kip2) protein was low. In cultured human endometrial stromal cells (ESCs), p27(kip1) mRNA levels were increased together with the decidual marker prolactin (prl), following treatment with 17beta-estradiol (E2) and progesterone (P4). At 1 nmol/L, the glucocorticoid receptor (GR) agonist dexamethasone (DEX) induced prl, p57(kip2) , and p27(kip1) mRNA in ESCs. Taken together, upregulation of p57(kip2) may play an important role in the decidual differentiation by P4 and growth inhibition of malignant cells in human endometrium. PMID- 22064388 TI - Risk-takers wanted. PMID- 22064389 TI - Preemptive genotyping trialed to prevent adverse drug reactions. PMID- 22064390 TI - New mouse models of autism highlight need for standardized tests. PMID- 22064391 TI - First drugs found to inhibit elusive cancer target. PMID- 22064392 TI - Stanford program gives discoveries a shot at commercialization. PMID- 22064393 TI - Massive biobank yields first results--with more to come. PMID- 22064394 TI - MS pipeline flowing, but niche remains for neuroprotection. PMID- 22064395 TI - Research organizations push back against clinical trials directive. PMID- 22064396 TI - Drug shortages may derail careers along with trials. PMID- 22064397 TI - Sequencing projects bring age-old wisdom to genomics. PMID- 22064398 TI - Malaria vaccine cuts risk in half in late-stage trial. PMID- 22064400 TI - Straight talk with... Steve Brown. Interview by Hannah Waters. PMID- 22064401 TI - A raw nerve. PMID- 22064402 TI - Autism, authenticated. PMID- 22064403 TI - Smart resource allocation needed to study 'legal highs'. PMID- 22064406 TI - Hepcidin in malaria superinfection: can findings be translated to humans? PMID- 22064407 TI - Tissue factor and obesity, a two-way street. PMID- 22064408 TI - Targeting osteoclast-osteoblast communication. PMID- 22064409 TI - Erythropoiesis lagging? pIgA1 steps in to assist Epo. PMID- 22064410 TI - SGK1: a fine balancing act for human pregnancy. PMID- 22064411 TI - An unSIRTain role in longevity. PMID- 22064412 TI - Unfolding neurodevelopmental disorders: found in translation. PMID- 22064413 TI - Unfolding neurodevelopmental disorders: the mystery of developing connections. PMID- 22064426 TI - Tumor angiogenesis: molecular pathways and therapeutic targets. AB - As angiogenesis is essential for tumor growth and metastasis, controlling tumor associated angiogenesis is a promising tactic in limiting cancer progression. The tumor microenvironment comprises numerous signaling molecules and pathways that influence the angiogenic response. Understanding how these components functionally interact as angiogenic stimuli or as repressors and how mechanisms of resistance arise is required for the identification of new therapeutic strategies. Achieving a durable and efficient antiangiogenic response will require approaches to simultaneously or sequentially target multiple aspects of the tumor microenvironment. PMID- 22064427 TI - The lymphatic vasculature in disease. AB - Blood vessels form a closed circulatory system, whereas lymphatic vessels form a one-way conduit for tissue fluid and leukocytes. In most vertebrates, the main function of lymphatic vessels is to collect excess protein-rich fluid that has extravasated from blood vessels and transport it back into the blood circulation. Lymphatic vessels have an important immune surveillance function, as they import various antigens and activated antigen-presenting cells into the lymph nodes and export immune effector cells and humoral response factors into the blood circulation. Defects in lymphatic function can lead to lymph accumulation in tissues, dampened immune responses, connective tissue and fat accumulation, and tissue swelling known as lymphedema. This review highlights the most recent developments in lymphatic biology and how the lymphatic system contributes to the pathogenesis of various diseases involving immune and inflammatory responses and its role in disseminating tumor cells. PMID- 22064428 TI - The neutrophil in vascular inflammation. AB - Here we focus on how neutrophils have a key regulatory role in vascular inflammation. Recent studies using advanced imaging techniques have yielded new insights into the mechanisms by which neutrophils contribute to defense against bacterial infections and also against sterile injury. In these settings, neutrophils are recruited by various mechanisms depending on the situation. We also describe how these processes may be disrupted in systemic infections, with a particular emphasis on mouse models of sepsis. Neutrophils are often immobilized in the lungs and liver during systemic infections, and this immobilization may be a mechanism through which bacteria can evade the innate immune response or allow neutrophils to form neutrophil extracellular traps that trap and kill bacteria in blood. The platelet is also an important player in sepsis, and we describe how it collaborates with neutrophils in the formation of neutrophil extracellular traps. PMID- 22064429 TI - Ischemia and reperfusion--from mechanism to translation. AB - Ischemia and reperfusion-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery. An imbalance in metabolic supply and demand within the ischemic organ results in profound tissue hypoxia and microvascular dysfunction. Subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Recent advances in understanding the molecular and immunological consequences of ischemia and reperfusion may lead to innovative therapeutic strategies for treating patients with ischemia and reperfusion-associated tissue inflammation and organ dysfunction. PMID- 22064430 TI - Under pressure: the search for the essential mechanisms of hypertension. AB - High blood pressure, or hypertension, is a very common disorder with a substantial impact on public health because of its associated complications. Despite the high prevalence of essential hypertension and years of research, the basic causes remain obscure. Here I review recent advances in understanding the pathophysiology of hypertension. I present a general overview of the field and, by necessity, use broad strokes to portray recent progress and place it in context. For this purpose, I use illustrative examples from the large number of important developments in hypertension research over the last five years. The intent of this review is to provide a sense of where the field is progressing, with an emphasis on work that sheds light on pathogenic mechanisms and that is therefore likely to inform new translational advances. PMID- 22064431 TI - Atherosclerosis: current pathogenesis and therapeutic options. AB - Coronary artery disease (CAD) arising from atherosclerosis is a leading cause of death and morbidity worldwide. The underlying pathogenesis involves an imbalanced lipid metabolism and a maladaptive immune response entailing a chronic inflammation of the arterial wall. The disturbed equilibrium of lipid accumulation, immune responses and their clearance is shaped by leukocyte trafficking and homeostasis governed by chemokines and their receptors. New pro- and anti-inflammatory pathways linking lipid and inflammation biology have been discovered, and genetic profiling studies have unveiled variations involved in human CAD. The growing understanding of the inflammatory processes and mediators has uncovered an intriguing diversity of targetable mechanisms that can be exploited to complement lipid-lowering therapies. Here we aim to systematically survey recently identified molecular mechanisms, translational developments and clinical strategies for targeting lipid-related inflammation in atherosclerosis and CAD. PMID- 22064432 TI - Arterial thrombosis--insidious, unpredictable and deadly. AB - The formation of blood clots--thrombosis--at sites of atherosclerotic plaque rupture is a major clinical problem despite ongoing improvements in antithrombotic therapy. Progress in identifying the pathogenic mechanisms regulating arterial thrombosis has led to the development of newer therapeutics, and there is general anticipation that these treatments will have greater efficacy and improved safety. However, major advances in this field require the identification of specific risk factors for arterial thrombosis in affected individuals and a rethink of the 'one size fits all' approach to antithrombotic therapy. PMID- 22064438 TI - Ferulic acid ethyl ester as a potential therapy in neurodegenerative disorders. AB - Oxidative stress is involved in the onset, progression and pathogenesis of a number of diseases including neurodegenerative diseases. It is critical to develop a pharmacological approach to combat oxidative stress which may reduce the risk of diseases and help in promoting healthy life. In an attempt to reduce the side effects associated with allopathic medicines a number of studies are now focusing on developing treatment regimens from naturally occurring plant products. In this review, the protective role of ferulic acid (4-hydroxy-3 methoxycinnamic acid) (FA), a naturally occurring antioxidant compound found in fruit, some vegetables, and grains, and its ethyl ester derivative are discussed with respect to neurodegeneration. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease. PMID- 22064433 TI - Stem cells and the vasculature. AB - Unraveling the contribution of stem and progenitor cells to blood vessel formation and, reciprocally, the importance of blood vessels to the production and function of stem and progenitor cells, has been a major focus of vascular research over the last decade, but has spawned many controversies. Here I review how vascular stem and progenitor cells contribute both vascular and nonvascular cells during development and in disease, and how nonvascular stem and progenitor cells might contribute to vascular lineages. I also discuss the role of the vasculature in forming stem and progenitor cell niches. Finally, I highlight the potential relevance of these relationships to disease etiology and treatment. PMID- 22064439 TI - 4-[Bis(4-fluorophenyl)methyl]piperazin-1-ium picrate. AB - The title compound {systematic name: 4-[bis(4-fluorophenyl)methyl]piperazin-1-ium 2,4,6-tri-nitro-phenolate}, C(17)H(19)F(2)N(2) (+).C(6)H(2)N(3)O(7) (-), is the picrate salt of a piperazine-supported amine bearing a benzhydryl substituent on one of its N atoms. During co-crystallisation, protonation took place on the N atom of the secondary amine functionality. The non-aromatic six-membered heterocycle adopts a chair conformation. In the crystal, N-H?O hydrogen bonds as well as C-H?O contacts connect the components into a three-dimensional network. PMID- 22064440 TI - 2-[(4-Meth-oxy-anilino)meth-yl]phenol. AB - In the title compound, C(14)H(15)NO(2), the dihedral angle between the two benzene rings is 71.10 (5) degrees . In the crystal, mol-ecules are linked by inter-molecular N-H?O, and O-H?N hydrogen bonds into a chain running parallel to the b axis. PMID- 22064441 TI - 3-(1,3-Dithio-lan-2-yl-idene)-1-(4-meth-oxy-phen-yl)pyridine-2,4(1H,3H)-dione. AB - In the title compound, C(15)H(13)NO(3)S(2), the dithiol-ane ring adopts a twisted conformation. The mol-ecule exhibits a V-shaped conformation, with a dihedral angle of 79.05 (7) degrees between the benzene ring and the pyridine ring. In the crystal, C-H?O inter-actions are observed. PMID- 22064442 TI - Quantitatively measuring in situ flows using a self-contained underwater velocimetry apparatus (SCUVA). AB - The ability to directly measure velocity fields in a fluid environment is necessary to provide empirical data for studies in fields as diverse as oceanography, ecology, biology, and fluid mechanics. Field measurements introduce practical challenges such as environmental conditions, animal availability, and the need for field-compatible measurement techniques. To avoid these challenges, scientists typically use controlled laboratory environments to study animal-fluid interactions. However, it is reasonable to question whether one can extrapolate natural behavior (i.e., that which occurs in the field) from laboratory measurements. Therefore, in situ quantitative flow measurements are needed to accurately describe animal swimming in their natural environment. We designed a self-contained, portable device that operates independent of any connection to the surface, and can provide quantitative measurements of the flow field surrounding an animal. This apparatus, a self-contained underwater velocimetry apparatus (SCUVA), can be operated by a single scuba diver in depths up to 40 m. Due to the added complexity inherent of field conditions, additional considerations and preparation are required when compared to laboratory measurements. These considerations include, but are not limited to, operator motion, predicting position of swimming targets, available natural suspended particulate, and orientation of SCUVA relative to the flow of interest. The following protocol is intended to address these common field challenges and to maximize measurement success. PMID- 22064443 TI - ALTered telomeres in response to telomere dysfunction. PMID- 22064444 TI - 6-Chloro-N-methyl-5-nitro-N-phenyl-pyrimidin-4-amine. AB - In the title compound, C(11)H(9)ClN(4)O(2), the dihedral angle between the aromatic rings is 79.67 (8) degrees . pi-pi stacking between centrosymmetrically related pairs of pyrimidine rings occurs along [100] [centroid-centroid separations = 3.4572 (8) and 3.5433 (7) A]. PMID- 22064447 TI - Valvular disease: the UK TAVI experience: insights from the 'real world'. PMID- 22064448 TI - Device therapy: Public-access AEDs improve neurologically intact survival after cardiac arrest. PMID- 22064450 TI - Surgery: No benefit of cerebral perfusion over hypothermia in pulmonary endarterectomy. PMID- 22064451 TI - Synthesis of a novel kind of carbon nanoparticle with large mesopores and macropores and its application as an oral vaccine adjuvant. AB - The purpose of this study is to develop a novel kind of adjuvant for oral vaccine delivery. In order to effectively prevent the degradation of antigens in the gastrointestinal tract and optimize the uptake for M cells, a novel kind of hydrophobic carbon nanoparticle (C1) with the size of 470nm was synthesized by taking silica as a template and sucrose as a carbon source. Notably, there were large mesopores and macropores mainly of 40-60nm, which made it to be excellent candidate as an antigen carrier. C1 was characterized using SEM, TEM and nitrogen adsorption. Following oral immunization with BSA loaded in C1, the IgG titer reached to a level almost equal to that of parenteral administration of antigen emulsified in Freund's complete adjuvant (FCA). Mucosal IgA was also detected in intestinal, salivary and vaginal secretions, suggesting an effective stimulation of mucosal immune response. Besides, both T-helper 1 and T-helper 2 (Th1 or Th2) mediated responses were induced. We believe that the research will help in the design of novel vaccine adjuvant for improvement their potential on modulation of immune response. PMID- 22064452 TI - All-trans retinoic acid loaded block copolymer nanoparticles efficiently induce cellular differentiation in HL-60 cells. AB - All-trans retinoic acid (atRA) is used in the differentiation therapy of Acute Promyelocytic Leukemia. However, its therapeutic success is limited by the appearance of relapse and recalcitrant cases, poor aqueous solubility and high degradability. In the current work, we prepared two types of atRA-loaded copolymer nanoparticles - PL1RA and PC1RA, based on poly(ethyleneglycol) (PEG) poly(l-lactide) and PEG-poly(epsilon-caprolactone), respectively. We then evaluated their physico-chemical properties and compared their differentiation inducing potential of HL-60 cells with free atRA. These nanoparticles were in the size range 100-150nm, possessed moderate colloidal stability and exhibited around 30% encapsulation efficiencies. In vitro release studies indicated pseudo-zero order release of a sustained nature, with PL1RA showing 71% and PC1RA exhibiting 84% drug release over a period of two weeks. Photostability measurements exhibited considerable increase in atRA photostability in the nanoparticle forms: 25% of the drug in PL1RA and 19% in PC1RA was intact as compared to only 5% for free atRA after 8h of light exposure. PL1RA and PC1RA exhibited efficacies comparable to free atRA in inducing HL-60 respiratory burst as assessed by nitroblue tetrazolium and 2',7'-dichlorodihydro fluorescein diacteate assays. The average CD11b expressions for atRA, PL1RA and PC1RA on day 5 of treatment were 58%, 49% and 60%, respectively. Post-differentiation apoptosis (~40%) and reduction in mitochondrial transmembrane potentials (~60-70%) were also comparable across all treatment groups. Therefore, our block copolymer nanoparticles, PL1RA and PC1RA, are attractive and effective vehicles for atRA delivery which maintain its activity and enhance its stability resulting in efficient induction of HL-60 differentiation. PMID- 22064453 TI - Controlled release of insulin from self-assembling nanofiber hydrogel, PuraMatrixTM: application for the subcutaneous injection in rats. AB - The concept of this research is, using the acetyl-(Arg-Ala-Asp-Ala)4-CONH2 peptide hydrosol (PuraMatrixTM, PM), to develop an new injectable formula of controlled insulin delivery for subcutaneous injection. PM has sol-gel phase transition behavior, and was developed as a scaffold in the field of tissue engineering. The aqueous media of the PM including insulin changed from a sol to a gel phase with increasing ion strength of phosphate ion and pH in working environments in vitro and in vivo. In this study, we examined the in vitro insulin dissolution behavior and the in vivo pharmacokinetics and pharmacodynamics after subcutaneous administration of PM-insulin sol (PM-Isol). In the in vitro release study, after PM-Isol was converted to a gel phase (PM Igel), PM concentration-dependent and controlled release of insulin were observed at the final concentrations of PM between 0.1% and 2.0% (w/v). The PM-Isol is changed to gel form in vivo, and exhibited a sustained-release pharmacokinetics of insulin, where PM concentration-dependent prolongation of efficacy was found. The plasma glucose level markedly decreased, and the lowest plasma glucose level was maintained up to 24h when 2.0% (w/v) PM-Isol was administered subcutaneously to rats. The PM-Isol, we developed here, is applicable for the wild-type of insulin, and increased the bioavailability and hypoglycemic efficacy of insulin after subcutaneous injection. Hence, the PM is a useful inactive ingredient to produce various types of control-released system of insulin by making just a few changes in PM content of the formulation. PMID- 22064454 TI - Targeting epidermal growth factor receptor in tumors: from conventional monoclonal antibodies via heavy chain-only antibodies to nanobodies. AB - The discovery of naturally occurring heavy chain only antibodies and their further development into small recombinant 'nanobodies' offers attractive applications in drug targeting. Here, we describe the properties of nanobodies that have been developed to target the epidermal growth factor receptor (EGFR) and contrast these to the characteristics of heavy chain only antibodies and conventional antibodies. EGFR is overexpressed in many tumors and is an attractive target for tumor-directed drug targeting. PMID- 22064455 TI - 1,1,1-Trifluoro-4-(thio-phen-2-yl)-4-[(2-{[4,4,4-trifluoro-3-oxo-1-(thio-phen-2 yl)but-1-en-1-yl]amino}-eth-yl)amino]-but-3-en-2-one. AB - The asymmetric unit of the diamine compound, C(18)H(14)F(3)N(2)O(2)S(2), consists of two mol-ecules; the C=C double bond has a Z configuration in the C(4)H(3)S-C=C C(=O)-C segment. The -NH-CH(2)-CH(2)-NH chain adopts a twisted U-shape. The amino group is an intra-molecular hydrogen-bond donor to the carbonyl group; the intra molecular hydrogen bond generates a six-membered ring. In both mol-ecules, the thienyl rings are disordered over two positions; the occupancies of the major components are 0.817 (4) and 0.778 (4) in one mol-ecule and 0.960 (4) and 0.665 (4) in the other. One of the trifluoro-methyl groups is disordered over two positions with the major component having 0.637 (8) occupancy. PMID- 22064456 TI - Robust generation of hepatocyte-like cells from human embryonic stem cell populations. AB - Despite progress in modelling human drug toxicity, many compounds fail during clinical trials due to unpredicted side effects. The cost of clinical studies are substantial, therefore it is essential that more predictive toxicology screens are developed and deployed early on in drug development (Greenhough et al 2010). Human hepatocytes represent the current gold standard model for evaluating drug toxicity, but are a limited resource that exhibit variable function. Therefore, the use of immortalised cell lines and animal tissue models are routinely employed due to their abundance. While both sources are informative, they are limited by poor function, species variability and/or instability in culture (Dalgetty et al 2009). Pluripotent stem cells (PSCs) are an attractive alternative source of human hepatocyte like cells (HLCs) (Medine et al 2010). PSCs are capable of self renewal and differentiation to all somatic cell types found in the adult and thereby represent a potentially inexhaustible source of differentiated cells. We have developed a procedure that is simple, highly efficient, amenable to automation and yields functional human HLCs (Hay et al 2008 ; Fletcher et al 2008 ; Hannoun et al 2010 ; Payne et al 2011 and Hay et al 2011). We believe our technology will lead to the scalable production of HLCs for drug discovery, disease modeling, the construction of extra-corporeal devices and possibly cell based transplantation therapies. PMID- 22064459 TI - Adaptive clinical trials in oncology. AB - Modern oncology drug development faces challenges very different from those of the past and it must adapt accordingly. The size and expense of phase III clinical trials continue to increase, but the success rate remains unacceptably low. Adaptive trial designs can make development more informative, addressing whether a drug is safe and effective while showing how it should be delivered and to whom. An adaptive design is one in which the accumulating data are used to modify the trial's course. Adaptive designs are ideal for addressing many questions at once. For example, a single trial might identify the appropriate patient population, dose and regimen, and therapeutic combinations, and then switch seamlessly into a phase III confirmatory trial. Adaptive designs rely on information, including from patients who have not achieved the trial's primary end point. Longitudinal models of biomarkers (including tumor burden assessed via imaging) enable predictions of primary end points. Taking a Bayesian perspective facilitates building an efficient and accurate trial, including using longitudinal information. A wholly new paradigm for drug development exemplifying personalized medicine is evinced by an adaptive trial called I-SPY2, in which drugs from many companies are evaluated in the same trial--a phase II screening process. PMID- 22064460 TI - Targeted therapies: adjuvant bisphosphonates--an option with low estrogen? PMID- 22064462 TI - Immunotherapy: a first for first-line therapy in NSCLC. PMID- 22064461 TI - Clinical radioimmunotherapy--the role of radiobiology. AB - Conventional external-beam radiation therapy is dedicated to the treatment of localized disease, whereas radioimmunotherapy represents an innovative tool for the treatment of local or diffuse tumors. Radioimmunotherapy involves the administration of radiolabeled monoclonal antibodies that are directed specifically against tumor-associated antigens or against the tumor microenvironment. Although many tumor-associated antigens have been identified as possible targets for radioimmunotherapy of patients with hematological or solid tumors, clinical success has so far been achieved mostly with radiolabeled antibodies against CD20 ((131)I-tositumomab and (90)Y-ibritumomab tiuxetan) for the treatment of lymphoma. In this Review, we provide an update on the current challenges aimed to improve the efficacy of radioimmunotherapy and discuss the main radiobiological issues associated with clinical radioimmunotherapy. PMID- 22064463 TI - (1E,1'E)-4,4'-[1,1'-(Hydrazine-1,2-diyl-idene)bis-(ethan-1-yl-1-yl idene)]diphenol dihydrate. AB - The asymmetric unit of the title compound, C(16)H(16)N(2)O(2).2H(2)O, contains one half-mol-ecule of diphenol and one water mol-ecule. The complete diphenol mol ecule is generated by a crystallographic inversion centre. In the mol-ecule, the central C(meth-yl)-C=N-N=C-C(meth-yl) plane makes a dihedral angle of 8.88 (6) degrees with its adjacent benzene ring. In the crystal, the components are linked by O-H?N and O-H?O hydrogen bonds into a three-dimensional network. The crystal structure is further stabilized by a weak C-H?pi inter-action. PMID- 22064464 TI - Ultrasound dye-assisted surgery (USDAS): a promising diagnostic and therapeutic tool for the treatment of cancer recurrences in the neck. AB - The evolution of new techniques for cancer surgery has led to important changes in cancer care in recent years. The endpoint of cancer treatment is now to treat the patient with minimum discomfort while respecting quality of life. New techniques, such as mini-invasive surgery, must respect the correct oncological indications, when technically feasible. The surgery for nodal spread or recurrence of disease, after previous surgery on T or T and N for neck cancer, can represent a diagnostic and therapeutic challenge, especially in the neck, which is characterized by small spaces and noble structures. Often lesions become enveloped in scar tissue and can be difficult to visualize during surgery, representing a genuine problem for the surgeon. Ultrasound dye-assisted surgery is a procedure that combines ultra-sound localization of pathological nodes with the use of methylene blue to mark diseased structures to simplify their visualization (and thus removal) in the surgical field. The technique is simple and can be used in surgically and oncologically experienced hands, even in hospitals that do not have sophisticated technology. PMID- 22064465 TI - Micromanaging aging with miRNAs: new messages from the nuclear envelope. AB - Over the last years, the discovery of microRNAs (miRNAs) has revolutionized the classic concepts of gene expression regulation and has introduced a new group of molecules that may contribute to the complex changes observed during aging. Although several Caenorhabditis elegans miRNAs have been proved to influence the nematode life span, the current knowledge about miRNA-mediated regulation of mammalian aging is still limited. Recently, we have analyzed the functional relevance of miRNAs in accelerate aging by using Zmpste24-/- mice, a murine model that phenocopies Hutchinson-Gilford progeria syndrome. These studies have revealed that the nuclear abnormalities present in these mice affect the expression levels of several miRNAs, including a marked upregulation of miR-1 and miR-29. Furthermore, we have found that the altered expression of these miRNAs may contribute to the progeroid phenotype of mutant mice by modulating the levels of key components of the somatroph axis and DNA damage response pathways. Here, we discuss these recent discoveries and summarize the present evidences regarding the involvement of aging-associated miRNAs or geromiRs in senescence and longevity regulation. PMID- 22064466 TI - Dbp5, Gle1-IP6 and Nup159: a working model for mRNP export. AB - Gene expression is a stepwise process involving distinct cellular processes including transcription, mRNA (mRNA) processing, mRNA export, and translation. As mRNAs are being synthesized, proteins associate with the RNA to form messenger ribonucleoprotein particles (mRNPs). Previous studies have demonstrated that the RNA-binding protein composition of these mRNPs is dynamic, changing as the mRNP moves through the different steps of gene expression, and playing a critical role in these events. An important step during this maturation process occurs at the cytoplasmic face of the nuclear pore complex (NPC) where the export protein Gle1 bound to inositol hexakisphosphate (IP 6) spatially activates the ATP-hydrolysis and mRNP-remodeling activity of the DEAD-box protein Dbp5. Recent work from our laboratory and others has provided important insights into the function and regulation of Dbp5. These include a more detailed explanation of the mechanism of Dbp5 RNP remodeling, the role of Gle1-IP6 in stimulating Dbp5 ATPase activity, and the identification of a novel paradigm for regulation of Dbp5 by Nup159. Based on in vitro biochemical assays, X-ray crystallography, and corresponding in vivo phenotypes, we propose here an updated model of the Dbp5 cycle during mRNP export through the NPC. This takes into account all available data and provides a platform for future studies. PMID- 22064467 TI - Epigenetic stability of repressed states involving the histone variant macroH2A revealed by nuclear transfer to Xenopus oocytes. AB - How various epigenetic mechanisms restrict chromatin plasticity to determine the stability of repressed genes is poorly understood. Nuclear transfer to Xenopus oocytes induces the transcriptional reactivation of previously silenced genes. Recent work suggests that it can be used to analyze the epigenetic stability of repressed states. The notion that the epigenetic state of genes is an important determinant of the efficiency of nuclear reprogramming is supported by the differential reprogramming of given genes from different starting epigenetic configurations. After nuclear transfer, transcription from the inactive X chromosome of post-implantation-derived epiblast stem cells is reactivated. However, the same chromosome is resistant to reactivation when embryonic fibroblasts are used. Here, we discuss different kinds of evidence that link the histone variant macroH2A to the increased stability of repressed states. We focus on developmentally regulated X chromosome inactivation and repression of autosomal pluripotency genes, where macroH2A may help maintain the long-term stability of the differentiated state of somatic cells. PMID- 22064468 TI - Dare to challenge the silence? Telomeric gene silencing revisited. AB - Gene silencing refers to position-dependent and promoter-independent repression of genes via the establishment and the maintenance of compacted heterochromatin. A very significant part of our knowledge on this phenomenon has been derived from studies in the yeasts S. cerevisiae and S. pombe. The gene silencing analyses in these species very often include the FOA-sensitivity assay, which detects the suppression of a reporter gene (URA3 in S. cerevisiae and URA4 in S. pombe) inserted at genomic locations of choice. Two recent studies have contested the validity of this assay and have set uneasy silence in the field. We are not certain how much of the previously acquired data truly deals with gene silencing. The current article comments on this challenge. PMID- 22064469 TI - Progeria Research Day at Brunel University. AB - Hutchinson-Gilford Progeria Syndrome (HGPS) is a severe premature aging syndrome that affects children. These children display characteristics associated with normal aging and die young usually from cardiovascular problems or stroke. Classical HGPS is caused by mutations in the gene encoding the nuclear structural protein lamin A. This mutation leads to a novel version of lamin A that retains a farnesyl group from its processing. This protein is called Progerin and is toxic to cellular function. Pre-lamin A is an immature version of lamin A and also has a farnesylation modification, which is cleaved in the maturation process to create lamin A. PMID- 22064470 TI - SUMO routes ribosome maturation. AB - The control of ribosome biogenesis is a critical cellular nodal point, which ensures that protein synthesis is coordinated with cell growth and proliferation. Prior to their cytoplasmic assembly the 40S and 60S ribosomal subunits pass through the nucleolus and the nucleoplasm via a maturation pathway that involves a set of non-coding RNAs and non-ribosomal regulatory trans-acting factors. In mammalian cells the inventory of the required protein components is still fragmentary and it is largely unclear what drives the subcellular transitions and the exchange of protein components along the maturation pathway. However, recent data indicate that the dynamic post-translational modification by the ubiquitin like SUMO modifier is critically involved in these processes. In particular, removal of SUMO from trans-acting factors by the SUMO-specific isopeptidase SENP3 is instrumental in the 60S maturation pathway in mammals. In an attempt to pinpoint the relevant targets of SENP3 we identified a novel SENP3-associated protein complex comprised of PELP1, TEX10 and WDR18. We demonstrated that this complex is involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the 60S ribosomal subunit. Importantly, we found that PELP1 is a SENP3-sensitive target of SUMO and observed that lack of SENP3-mediated desumoylation prevents the nucleolar partitioning of the PELP1 TEX10-WDR18 complex. SUMO-dependent subnuclear trafficking may thus assist in coordinating the rate of ribosome formation. Here we propose that sumoylation of PELP1 serves as a quality control mechanism that restricts pre-mature loading of the PELP1-WDR18-TEX10 complex to 60S particles thereby limiting ribosome maturation. We further hypothesize that the PELP1-associated AAA-ATPase MDN1 may be part of this surveillance pathway. PMID- 22064471 TI - Physical breakdown of the nuclear envelope is not necessary for breaking its barrier function. AB - During mitosis in higher eukaryotic cells, nuclear envelope breakdown (NEBD) occurs and leads to the disassembly of the nuclear membrane and nuclear pore complexes (NPC). This brings about a mixing of nuclear and cytoplasmic macromolecules (open mitosis). On the other hand, in many fungi, mitosis occurs without NEBD (closed mitosis). In a recent study, we reported a novel phenomenon in a closed mitosis organism, Schizosaccharomyces pombe: mixing of nuclear and cytoplasmic proteins occurred in meiosis without breakdown of the nuclear membrane or disassembly of nuclear pore complexes. We designated this event virtual nuclear envelope breakdown (V-NEBD). The key event in V-NEBD is nuclear translocation of Rna1, a RanGAP1 homologue in S. pombe. This leads to collapse of the Ran-GTP gradient across the nuclear envelope (NE) and occurs coincidently with V-NEBD. Thus, the barrier function of the NE can be abated without its physical breakdown through modulation of the Ran-GTP gradient. PMID- 22064472 TI - Isolation & characterization of Hoechst(low) CD45(negative) mouse lung mesenchymal stem cells. AB - Tissue resident mesenchymal stem cells (MSC) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis and tumor formation. Taken together these studies suggest that resident lung MSC play a role during pulmonary tissue homeostasis, injury and repair during diseases such as pulmonary fibrosis (PF) and arterial hypertension (PAH). Here we describe a technology to define a population of resident lung MSC. The definition of this population in vivo pulmonary tissue using a define set of markers facilitates the repeated isolation of a well-characterized stem cell population by flow cytometry and the study of a specific cell type and function. PMID- 22064474 TI - Ambulatory surgery center and general hospital competition: entry decisions and strategic choices. AB - BACKGROUND: General hospitals are consistently under pressure to control cost and improve quality. In addition to mounting payers' demands, hospitals operate under evolving market conditions that might threaten their survival. While hospitals traditionally were concerned mainly with competition from other hospitals, today's reimbursement schemes and entrepreneurial activities encouraged the proliferation of outpatient facilities such as ambulatory surgery centers (ASCs) that can jeopardize hospitals' survival. PURPOSE: The purpose of this article was to examine the relationship between ASCs and general hospitals. More specifically, we apply the niche overlap theory to study the impact that competition between ASCs and general hospitals has on the survival chances of both of these organizational populations. METHODOLOGY: Our analysis examined interpopulation competition in models of organizational mortality and market demand. We utilized Cox proportional hazard models to evaluate the impact of competition from each on ASC and hospital exit while controlling for market factors. We relied on two data sets collected and developed by Florida's Agency for Health Care Administration: outpatient facility licensure data and inpatient and outpatient surgical procedure data. FINDINGS: Although ASCs do tend to exit markets in which there are high levels of ASC competition, we found no evidence to suggest that ASC exit rates are affected by hospital density. On the other hand, hospitals not only tend to exit markets with high levels of hospital competition but also experience high exit rates in markets with high ASC density. PRACTICE IMPLICATIONS: The implications from our study differ for ASCs and hospitals. When making decisions about market entry, ASCs should choose their markets according to the following: demand for outpatient surgery, number of physicians who would practice in the surgery center, and the number of surgery centers that already exist in the market. Hospitals, on the other hand, should account for competition from ASCs while making market-entry decisions and while developing their strategic plans. PMID- 22064475 TI - Hospital electronic medical record enterprise application strategies: do they matter? AB - BACKGROUND: Successful implementations and the ability to reap the benefits of electronic medical record (EMR) systems may be correlated with the type of enterprise application strategy that an administrator chooses when acquiring an EMR system. Moreover, identifying the most optimal enterprise application strategy is a task that may have important linkages with hospital performance. PURPOSE: This study explored whether hospitals that have adopted differential EMR enterprise application strategies concomitantly differ in their overall efficiency. Specifically, the study examined whether hospitals with a single vendor strategy had a higher likelihood of being efficient than those with a best of-breed strategy and whether hospitals with a best-of-suite strategy had a higher probability of being efficient than those with best-of-breed or single vendor strategies. A conceptual framework was used to formulate testable hypotheses. METHODOLOGY: A retrospective cross-sectional approach using data envelopment analysis was used to obtain efficiency scores of hospitals by EMR enterprise application strategy. A Tobit regression analysis was then used to determine the probability of a hospital being inefficient as related to its EMR enterprise application strategy, while moderating for the hospital's EMR "implementation status" and controlling for hospital and market characteristics. FINDINGS: The data envelopment analysis of hospitals suggested that only 32 hospitals were efficient in the study's sample of 2,171 hospitals. The results from the post hoc analysis showed partial support for the hypothesis that hospitals with a best-of-suite strategy were more likely to be efficient than those with a single-vendor strategy. PRACTICE IMPLICATIONS: This study underscores the importance of understanding the differences between the three strategies discussed in this article. On the basis of the findings, hospital administrators should consider the efficiency associations that a specific strategy may have compared with another prior to moving toward an enterprise application strategy. PMID- 22064476 TI - A U1-U2 snRNP interaction network during intron definition. AB - The assembly of prespliceosomes is responsible for selection of intron sites for splicing. U1 and U2 snRNPs recognize 5' splice sites and branch sites, respectively; although there is information regarding the composition of these complexes, little is known about interaction among the components or between the two snRNPs. Here we describe the protein network of interactions linking U1 and U2 snRNPs with the ATPase Prp5, important for branch site recognition and fidelity during the first steps of the reaction, using fission yeast Schizosaccharomyces pombe. The U1 snRNP core protein U1A binds to a novel SR-like protein, Rsd1, which has homologs implicated in transcription. Rsd1 also contacts S. pombe Prp5 (SpPrp5), mediated by SR-like domains in both proteins. SpPrp5 then contacts U2 snRNP through SF3b, mediated by a conserved DPLD motif in Prp5. We show that mutations in this motif have consequences not only in vitro (defects in prespliceosome formation) but also in vivo, yielding intron retention and exon skipping defects in fission yeast and altered intron recognition in budding yeast Saccharomyces cerevisiae, indicating that the U1-U2 network provides critical, evolutionarily conserved contacts during intron definition. PMID- 22064477 TI - The RecQ4 orthologue Hrq1 is critical for DNA interstrand cross-link repair and genome stability in fission yeast. AB - Of the five human RecQ family helicases, RecQ4, BLM, and WRN suppress distinct genome instability-linked diseases with severe phenotypes, often with indeterminate etiologies. Here, we functionally define Hrq1, a novel orthologue of RecQ4 from fission yeast. Biochemical analysis of Hrq1 reveals a DEAH box- and ATP-dependent 3'-5' helicase activity on various DNA substrates, including bubbles but not blunt duplexes, characteristic of the RecQ family. Cells lacking Hrq1 suffer spontaneous genomic instability and, consequently, require homologous recombination repair and the DNA damage checkpoint for viability. Hrq1 supports the nucleotide excision repair of DNA damage caused by the chemotherapeutic agent cisplatin and, in certain genetic contexts, UV light. Genetic epistasis analyses reveal that Hrq1 acts parallel to the PCNA/Ubc13/Mms2-dependent postreplication repair (PRR) pathway. Thus, in hrq1Delta cells, lesions are channeled through the PRR pathway, yielding hyper-recombinant and mutator phenotypes; analogous defects may underlie the genetic instability and diseases associated with RecQ4 dysfunction. PMID- 22064478 TI - Regulation of estrogen receptor alpha N-terminus conformation and function by peptidyl prolyl isomerase Pin1. AB - Estrogen receptor alpha (ERalpha), a key driver of growth in the majority of breast cancers, contains an unstructured transactivation domain (AF1) in its N terminus that is a convergence point for growth factor and hormonal activation. This domain is controlled by phosphorylation, but how phosphorylation impacts AF1 structure and function is unclear. We found that serine 118 (S118) phosphorylation of the ERalpha AF1 region in response to estrogen (agonist), tamoxifen (antagonist), and growth factors results in recruitment of the peptidyl prolyl cis/trans isomerase Pin1. Phosphorylation of S118 is critical for Pin1 binding, and mutation of S118 to alanine prevents this association. Importantly, Pin1 isomerizes the serine118-proline119 bond from a cis to trans isomer, with a concomitant increase in AF1 transcriptional activity. Pin1 overexpression promotes ligand-independent and tamoxifen-inducible activity of ERalpha and growth of tamoxifen-resistant breast cancer cells. Pin1 expression correlates with proliferation in ERalpha-positive rat mammary tumors. These results establish phosphorylation-coupled proline isomerization as a mechanism modulating AF1 functional activity and provide insight into the role of a conformational switch in the functional regulation of the intrinsically disordered transactivation domain of ERalpha. PMID- 22064479 TI - TIN2 stability is regulated by the E3 ligase Siah2. AB - Telomeres are coated by shelterin, a six-subunit complex that is required for protection and replication of chromosome ends. The central subunit TIN2, with binding sites to three subunits (TRF1, TRF2, and TPP1), is essential for stability and function of the complex. Here we show that TIN2 stability is regulated by the E3 ligase Siah2. We demonstrate that TIN2 binds to Siah2 and is ubiquitylated in vivo. We show using purified proteins that Siah2 acts as an E3 ligase to directly ubiquitylate TIN2 in vitro. Depletion of Siah2 led to stabilization of TIN2 protein, indicating that Siah2 regulates TIN2 protein levels in vivo. Overexpression of Siah2 in human cells led to loss of TIN2 at telomeres that was dependent on the presence of the catalytic RING domain of Siah2. In contrast to RNAi-mediated depletion of TIN2 that led to loss of TRF1 and TRF2 at telomeres, Siah2-mediated depletion of TIN2 allowed TRF1 and TRF2 to remain on telomeres, indicating a different fate for shelterin subunits when TIN2 is depleted posttranslationally. TPP1 was lost from telomeres, although its protein level was not reduced. We speculate that Siah2-mediated removal of TIN2 may allow dynamic remodeling of the shelterin complex and its associated factors during the cell cycle. PMID- 22064480 TI - Selective signaling by Akt1 controls osteoblast differentiation and osteoblast mediated osteoclast development. AB - Maintaining optimal bone integrity, mass, and strength throughout adult life requires ongoing bone remodeling, which involves coordinated activity between actions of bone-resorbing osteoclasts and bone forming-osteoblasts. Osteoporosis is a disorder of remodeling in which bone resorption outstrips deposition, leading to diminished bone mass and an increased risk of fractures. Here we identify Akt1 as a unique signaling intermediate in osteoblasts that can control both osteoblast and osteoclast differentiation. Targeted knockdown of Akt1 in mouse primary bone marrow stromal cells or in a mesenchymal stem cell line or genetic knockout of Akt1 stimulated osteoblast differentiation secondary to increased expression of the osteogenic transcription factor Runx2. Despite enhanced osteoblast differentiation, coupled osteoclastogenesis in Akt1 deficiency was markedly inhibited, with reduced accumulation of specific osteoclast mRNAs and proteins and impaired fusion to form multinucleated osteoclasts, defects secondary to diminished production of receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (m-CSF), critical osteoblast-derived osteoclast differentiation factors. Delivery of recombinant lentiviruses encoding Akt1 but not Akt2 to Akt1-deficient osteoblast progenitors reversed the increased osteoblast differentiation and, by boosting accumulation of RANKL and m-CSF, restored normal osteoclastogenesis, as did the addition of recombinant RANKL to conditioned culture medium from Akt1-deficient osteoblasts. Our results support the idea that targeted inhibition of Akt1 could lead to therapeutically useful net bone acquisition, and they indicate that closely related Akt1 and Akt2 exert distinct effects on cellular differentiation pathways. PMID- 22064481 TI - Mechanistic basis for RAG discrimination between recombination sites and the off target sites of human lymphomas. AB - During V(D)J recombination, RAG targeting to correct sites versus off-target sites relies on both DNA sequence features and on chromatin marks. Kinetic analysis using the first highly active full-length purified RAG1/RAG2 complexes has now allowed us to define the important catalytic features of this complex. We found that the overall rate of nicking, but not hairpinning, is critical for the discrimination between correct (optimal) versus off-target (suboptimal) sites used in human T-cell lymphomas, and we show that the C-terminal portion of RAG2 is required for this. This type of kinetic analysis permits us to analyze only the catalytically active RAG complex, in contrast to all other methods, which are unavoidably confounded by mixture with inactive RAG complexes. Moreover, we can distinguish the two major features of any enzymatic catalysis: the binding constant (K(D)) and the catalytic turnover rate, k(cat). Beyond a minimal essential threshold of heptamer quality, further suboptimal heptamer deviations primarily reduce the catalytic rate constant k(cat) for nicking. Suboptimal nonamers reduce not only the binding of the RAG complex to the recombination site (K(D)) but also the catalytic rate constant, consistent with a tight interaction between the RAG complex and substrate during catalysis. These features explain many aspects of RAG physiology and pathophysiology. PMID- 22064482 TI - Hypergrowth mTORC1 signals translationally activate the ARF tumor suppressor checkpoint. AB - The ARF tumor suppressor is a potent sensor of hyperproliferative cues emanating from oncogenic signaling. ARF responds to these cues by eliciting a cell cycle arrest, effectively abating the tumorigenic potential of these stimuli. Prior reports have demonstrated that oncogenic Ras(V12) signaling induces ARF through a mechanism mediated by the Dmp1 transcription factor. However, we now show that ARF protein is still induced in response to Ras(V12) in the absence of Dmp1 through the enhanced translation of existing Arf mRNAs. Here, we report that the progrowth Ras/tuberous sclerosis complex (TSC)/mTORC1 signaling pathway regulates ARF protein expression and triggers ARF-mediated tumor suppression through a novel translational mechanism. Hyperactivation of mTORC1 through Tsc1 loss resulted in a significant increase in ARF expression, activation of the p53 pathway, and a dramatic cell cycle arrest, which were completely reversed upon Arf deletion. ARF protein induced from Ras(V12) in the absence of Dmp1 repressed anchorage-independent colony formation in soft agar and tumor burden in an allograft model. Taken together, our data demonstrate the ability of the ARF tumor suppressor to respond to hypergrowth stimuli to prevent unwarranted tumor formation. PMID- 22064483 TI - Frat is a phosphatidylinositol 3-kinase/Akt-regulated determinant of glycogen synthase kinase 3beta subcellular localization in pluripotent cells. AB - Suppressing the activity of Gsk3beta is critical for maintenance of murine pluripotent stem cells. In murine embryonic stem cells (mESCs), Gsk3beta is inhibited by multiple mechanisms, including its inhibitory phosphorylation on serine 9 by protein kinase B (Akt), a major effector of the canonical phosphatidylinositol 3-kinase (PI3K) pathway. A second PI3K/Akt-regulated mechanism promotes the nuclear export of Gsk3beta, thereby restricting its access to nuclear substrates such as c-myc and beta-catenin. Although Gsk3beta shuttles between the nucleus and cytoplasm under self-renewing conditions, its localization is primarily cytoplasmic because its rate of nuclear export exceeds its rate of nuclear import. In this report, we show that Gsk3beta is exported from the nucleus in a complex with Frat. Loss of PI3K/Akt activity results in dissociation of this complex and retention of Gsk3beta in the nucleus. Frat continues to shuttle between the nucleus and cytoplasm under these conditions and remains predominantly in the cytoplasm. These results indicate that Frat carries Gsk3beta out of the nucleus under self-renewing conditions and that PI3K regulates this by promoting its association with Frat. These findings provide new links between PI3K/Akt signaling and regulation of Gsk3beta activity by Frat, an oncogene previously shown to cooperate with Myc in tumorigenesis. PMID- 22064484 TI - RNF34 is a cold-regulated E3 ubiquitin ligase for PGC-1alpha and modulates brown fat cell metabolism. AB - The transcriptional coactivator PGC-1alpha is a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell. PGC-1alpha is a short-lived protein, and the molecular components that control PGC-1alpha turnover and their functional importance in energy metabolism are largely unknown. Here we performed a luciferase-based overexpression screen and identified a Ring-finger-containing protein, RNF34, as a specific E3 ubiquitin ligase for PGC-1alpha. RNF34 is a nuclear protein that interacts with and ubiquitinates PGC-1alpha to promote its turnover. Interestingly, RNF34 binds to the C-terminal half of PGC-1alpha and targets it for degradation independently of the previously identified N-terminal phosphodegron motif. In brown fat cells, knockdown of RNF34 increases the endogenous PGC-1alpha protein level, uncoupling protein 1 (UCP1) expression, and oxygen consumption, while the opposite effects are observed in brown fat cells ectopically expressing wild-type RNF34 but not in cells expressing the ligase activity-defective mutant. Moreover, cold exposure and beta3-adrenergic receptor signaling, conditions that induce PGC-1alpha expression, suppress RNF34 expression in the brown fat cell, indicating a physiological relevance of this E3 ligase in thermogenesis. Our results reveal that RNF34 is a bona fide E3 ubiquitin ligase for PGC-1alpha and negatively regulates brown fat cell metabolism. PMID- 22064485 TI - Satb1 ablation alters temporal expression of immediate early genes and reduces dendritic spine density during postnatal brain development. AB - Complex behaviors, such as learning and memory, are associated with rapid changes in gene expression of neurons and subsequent formation of new synaptic connections. However, how external signals are processed to drive specific changes in gene expression is largely unknown. We found that the genome organizer protein Satb1 is highly expressed in mature neurons, primarily in the cerebral cortex, dentate hilus, and amygdala. In Satb1-null mice, cortical layer morphology was normal. However, in postnatal Satb1-null cortical pyramidal neurons, we found a substantial decrease in the density of dendritic spines, which play critical roles in synaptic transmission and plasticity. Further, we found that in the cerebral cortex, Satb1 binds to genomic loci of multiple immediate early genes (IEGs) (Fos, Fosb, Egr1, Egr2, Arc, and Bdnf) and other key neuronal genes, many of which have been implicated in synaptic plasticity. Loss of Satb1 resulted in greatly alters timing and expression levels of these IEGs during early postnatal cerebral cortical development and also upon stimulation in cortical organotypic cultures. These data indicate that Satb1 is required for proper temporal dynamics of IEG expression. Based on these findings, we propose that Satb1 plays a critical role in cortical neurons to facilitate neuronal plasticity. PMID- 22064486 TI - Drosophila Pumilio protein contains multiple autonomous repression domains that regulate mRNAs independently of Nanos and brain tumor. AB - Drosophila melanogaster Pumilio is an RNA-binding protein that potently represses specific mRNAs. In developing embryos, Pumilio regulates a key morphogen, Hunchback, in collaboration with the cofactor Nanos. To investigate repression by Pumilio and Nanos, we created cell-based assays and found that Pumilio inhibits translation and enhances mRNA decay independent of Nanos. Nanos robustly stimulates repression through interactions with the Pumilio RNA-binding domain. We programmed Pumilio to recognize a new binding site, which garners repression of new target mRNAs. We show that cofactors Brain Tumor and eIF4E Homologous Protein are not obligatory for Pumilio and Nanos activity. The conserved RNA binding domain of Pumilio was thought to be sufficient for its function. Instead, we demonstrate that three unique domains in the N terminus of Pumilio possess the major repressive activity and can function autonomously. The N termini of insect and vertebrate Pumilio and Fem-3 binding factors (PUFs) are related, and we show that corresponding regions of human PUM1 and PUM2 have repressive activity. Other PUF proteins lack these repression domains. Our findings suggest that PUF proteins have evolved new regulatory functions through protein sequences appended to their conserved PUF repeat RNA-binding domains. PMID- 22064487 TI - Developmental regulation of microRNA expression in Schwann cells. AB - Schwann cell differentiation and subsequent myelination of the peripheral nervous system require the action of several transcription factors, including Sox10, which is vital at multiple stages of development. The transition from immature to myelinating Schwann cell is also regulated posttranscriptionally and depends upon Dicer-mediated processing of microRNAs (miRNAs). Although specific miRNA targets have begun to be identified, the mechanisms establishing the dynamic regulation of miRNA expression have not been elucidated. We performed expression profiling studies and identified 225 miRNAs differentially expressed during peripheral myelination. A subset of 9 miRNAs is positively regulated by Sox10, including miR 338 which has been implicated in oligodendrocyte maturation. In vivo chromatin immunoprecipitation (ChIP) of sciatic nerve cells revealed a Sox10 binding site upstream of an alternate promoter within the Aatk gene, which hosts miR-338. Sox10 occupied this site in spinal cord ChIP experiments, suggesting a similar regulatory mechanism in oligodendrocytes. Cancer profiling studies have identified clusters of miRNAs that regulate proliferation, termed "oncomirs." In Schwann cells, the expression of many of these proproliferative miRNAs was reduced in the absence of Sox10. Finally, Schwann cells with reduced Sox10 and oncomir expression have an increase in the CDK inhibitor p21 and a concomitant reduction in cell proliferation. PMID- 22064488 TI - Transanal single port surgery: selecting a suitable access port in a porcine model. AB - Single port surgery of rectal tumors may be associated with a shorter learning curve and fewer costs than transanal endoscopic microsurgery. The authors aimed to select the most optimal single access port for transanal employment. Four single access ports (GelPOINT, TriPort, SSL Access System, and SILS) were tested in 2 pigs. Insertion feasibility and intraoperative features of each port were assessed. A rectal excision was attempted using the most suitable port. Insertion of GelPOINT was impossible. SILS and TriPort were easily inserted; however, insufficient stability demanded manual fixation. CO2 leaked through the TriPort trocar ports. Insertion of the 2-cm SSL Access System retractor was difficult, but pneumorectum and surgical circumstances were favorable. Single port transanal surgery may be a promising alternative for transanal endoscopic microsurgery. The SSL Access System was found the most suitable for this indication in a porcine model. PMID- 22064489 TI - Single-port gynecologic surgery with a novel surgical platform. AB - BACKGROUND: Laparoendoscopic single-site surgery (LESS) allows better cosmesis and decreased pain when compared with traditional laparoscopy (TL). Instrument crowding and diminished triangulation are limitations. This study evaluates a novel single-port surgical platform (NSP) designed to facilitate the transition from TL to LESS (TransEnterix SPIDER, Durham, NC). METHODS: NSP and TL were compared using standardized dry lab tasks. Feasibility of NSP in gynecology was assessed using the porcine model. RESULTS: Completion times with NSP were longer for ring transfer (P = .025) and trended longer for disc cutting (P = .074). Disc cutting accuracy was lower with NSP versus TL (P = .008). NSP operative times for hysterectomy, pelvic and para-aortic node dissection were 22.3, 13.3, and 26 minutes, respectively, without complications. Fatigue and lack of integrated bipolar cautery were limitations of NSP. CONCLUSION: While application of NSP to gynecology appears feasible, lower performance when compared with TL underscores the need for caution when applying NSP to humans. PMID- 22064490 TI - You can't touch this: touch-free navigation through radiological images. AB - Keyboards, mice, and touch screens are a potential source of infection or contamination in operating rooms, intensive care units, and autopsy suites. The authors present a low-cost prototype of a system, which allows for touch-free control of a medical image viewer. This touch-free navigation system consists of a computer system (IMac, OS X 10.6 Apple, USA) with a medical image viewer (OsiriX, OsiriX foundation, Switzerland) and a depth camera (Kinect, Microsoft, USA). They implemented software that translates the data delivered by the camera and a voice recognition software into keyboard and mouse commands, which are then passed to OsiriX. In this feasibility study, the authors introduced 10 medical professionals to the system and asked them to re-create 12 images from a CT data set. They evaluated response times and usability of the system compared with standard mouse/keyboard control. Users felt comfortable with the system after approximately 10 minutes. Response time was 120 ms. Users required 1.4 times more time to re-create an image with gesture control. Users with OsiriX experience were significantly faster using the mouse/keyboard and faster than users without prior experience. They rated the system 3.4 out of 5 for ease of use in comparison to the mouse/keyboard. The touch-free, gesture-controlled system performs favorably and removes a potential vector for infection, protecting both patients and staff. Because the camera can be quickly and easily integrated into existing systems, requires no calibration, and is low cost, the barriers to using this technology are low. PMID- 22064492 TI - Diabetes: tissue bacteria predict diabetes onset. PMID- 22064493 TI - The worldwide epidemiology of type 2 diabetes mellitus--present and future perspectives. AB - Over the past three decades, the number of people with diabetes mellitus has more than doubled globally, making it one of the most important public health challenges to all nations. Type 2 diabetes mellitus (T2DM) and prediabetes are increasingly observed among children, adolescents and younger adults. The causes of the epidemic of T2DM are embedded in a very complex group of genetic and epigenetic systems interacting within an equally complex societal framework that determines behavior and environmental influences. This complexity is reflected in the diverse topics discussed in this Review. In the past few years considerable emphasis has been placed on the effect of the intrauterine environment in the epidemic of T2DM, particularly in the early onset of T2DM and obesity. Prevention of T2DM is a 'whole-of-life' task and requires an integrated approach operating from the origin of the disease. Future research is necessary to better understand the potential role of remaining factors, such as genetic predisposition and maternal environment, to help shape prevention programs. The potential effect on global diabetes surveillance of using HbA(1c) rather than glucose values in the diagnosis of T2DM is also discussed. PMID- 22064498 TI - Surgery: benign thyroid disease-total or subtotal thyroidectomy? PMID- 22064500 TI - Reproductive endocrinology: adverse pregnancy outcomes in polycystic ovary syndrome. PMID- 22064502 TI - Autoimmunity: Celiac disease in T1DM-the need to look long term. AB - Does untreated celiac disease associated with type 1 diabetes mellitus worsen microvascular outcomes? Previous studies have concluded that a gluten-free diet offers no major benefit for glycemic control, whereas Leeds and colleagues provide preliminary data to the contrary. The question awaits a long-term prospective study or a clinical trial. PMID- 22064504 TI - Interpersonal problems associated with multidimensional personality questionnaire traits in women during the transition to adulthood. AB - Personality traits are known to be associated with a host of important life outcomes, including interpersonal dysfunction. The interpersonal circumplex offers a comprehensive system for articulating the kinds of interpersonal problems associated with personality traits. In the current study, traits as measured by the Multidimensional Personality Questionnaire in a sample of 124 young women were correlated with interpersonal dysfunction as measured by the Inventory of Interpersonal Problems-Circumplex. Results suggest that Multidimensional Personality Questionnaire traits vary in their associations with interpersonal distress and in their coverage of specific kinds of interpersonal difficulties among women undergoing the transition to adulthood. PMID- 22064505 TI - Experimental generation of carcinoma-associated fibroblasts (CAFs) from human mammary fibroblasts. AB - Carcinomas are complex tissues comprised of neoplastic cells and a non-cancerous compartment referred to as the 'stroma'. The stroma consists of extracellular matrix (ECM) and a variety of mesenchymal cells, including fibroblasts, myofibroblasts, endothelial cells, pericytes and leukocytes (1-3). The tumour associated stroma is responsive to substantial paracrine signals released by neighbouring carcinoma cells. During the disease process, the stroma often becomes populated by carcinoma-associated fibroblasts (CAFs) including large numbers of myofibroblasts. These cells have previously been extracted from many different types of human carcinomas for their in vitro culture. A subpopulation of CAFs is distinguishable through their up-regulation of alpha-smooth muscle actin (alpha-SMA) expression(4,5). These cells are a hallmark of 'activated fibroblasts' that share similar properties with myofibroblasts commonly observed in injured and fibrotic tissues (6). The presence of this myofibroblastic CAF subset is highly related to high-grade malignancies and associated with poor prognoses in patients. Many laboratories, including our own, have shown that CAFs, when injected with carcinoma cells into immunodeficient mice, are capable of substantially promoting tumourigenesis (7-10). CAFs prepared from carcinoma patients, however, frequently undergo senescence during propagation in culture limiting the extensiveness of their use throughout ongoing experimentation. To overcome this difficulty, we developed a novel technique to experimentally generate immortalised human mammary CAF cell lines (exp-CAFs) from human mammary fibroblasts, using a coimplantation breast tumour xenograft model. In order to generate exp-CAFs, parental human mammary fibroblasts, obtained from the reduction mammoplasty tissue, were first immortalised with hTERT, the catalytic subunit of the telomerase holoenzyme, and engineered to express GFP and a puromycin resistance gene. These cells were coimplanted with MCF-7 human breast carcinoma cells expressing an activated ras oncogene (MCF-7-ras cells) into a mouse xenograft. After a period of incubation in vivo, the initially injected human mammary fibroblasts were extracted from the tumour xenografts on the basis of their puromycin resistance (11). We observed that the resident human mammary fibroblasts have differentiated, adopting a myofibroblastic phenotype and acquired tumour-promoting properties during the course of tumour progression. Importantly, these cells, defined as exp-CAFs, closely mimic the tumour-promoting myofibroblastic phenotype of CAFs isolated from breast carcinomas dissected from patients. Our tumour xenograft-derived exp-CAFs therefore provide an effective model to study the biology of CAFs in human breast carcinomas. The described protocol may also be extended for generating and characterising various CAF populations derived from other types of human carcinomas. PMID- 22064506 TI - 3,3'-Dibenzyl-1,1'-[naphthalene-1,4-diylbis(methyl-ene)]di(1H-imidazol-3-ium) bis (hexa-fluoro-phosphate). AB - In the title N-heterocyclic carbene compound, C(32)H(30)N(4) (2+).2PF(6) (-), the mean plane of the naphthalene ring system makes dihedral angles of 79.15 (15) and 76.85 (16) with the imidazole rings and 56.15 (19) and 80.56 (16) degrees with the benzene rings. An intra-molecular C-H?N hydrogen bond occurs. The crystal structure is stabilized by C-H?F inter-actions. In addition, pi-pi inter-actions [centroid-centroid distances = 3.848 (1) and 3.574 (3) A] are observed. The nine equatorial F atoms in the two PF(6) (-) anions were disordered over two positions with occupancy ratios of 0.545 (10):0.455 (10) and 0.793 (11):0.207 (11) in the two anions. PMID- 22064507 TI - CDPK-driven changes in the intracellular ROS level and plant secondary metabolism. AB - Heterologous expression of a constitutively active calcium-dependent protein kinase (CDPK) gene was previously shown to increase secondary metabolite production in cultured cells of Rubia cordifolia, but the critical question of how CDPK activates secondary metabolism remains to be answered. In this article, we report that the expression of the Arabidopsis CDPK gene, AtCPK1, in R. cordifolia cells caused moderate and stable elevation of intracellular reactive oxygen species (ROS) levels. In contrast, the non-active, mutated AtCPK1 gene did not cause such an effect. The active AtCPK1 also increased cell size, likely by restricting cell division. These results are consistent with the model in which constitutive expression of AtCPK1 mimics the effects of elicitors, acting on secondary metabolism via the activation of ROS production. PMID- 22064508 TI - Online homology modelling as a means of bridging the sequence-structure gap. AB - For even the best-studied species, there is a large gap in their representation in the protein databank (PDB) compared to within sequence databases. Typically, less than 2% of sequences are represented in the PDB. This is partly due to the considerable experimental challenge and manual inputs required to solve three dimensional structures by methods such as X-ray diffraction and multi-dimensional nuclear magnetic resonance (NMR) spectroscopy in comparison to high-throughput sequencing. This gap is made even wider by the high level of redundancy within the PDB and under-representation of some protein categories such as membrane associated proteins which comprise approximately 25% of proteins encoded in genomes. A traditional route to closing the sequence-structure gap is offered by homology modelling whereby the sequence of a target protein is modelled on a template represented in the PDB using in silico energy minimisation approaches. More recently, online homology servers have become available which automatically generate models from proffered sequences. However, many online servers give little indication of the structural plausibility of the generated model. In this paper, the online homology server Geno3D will be described. This server uses similar software to that used in modelling structures during structure determination and thus generates data allowing determination of the structural plausibility of models. For illustration, modelling of a chemotaxis protein (CheY) from Pseudomononas entomophila L48 (accession YP_609298) on a template (PDB id. 1mvo), the phosphorylation domain of an outer membrane protein PhoP from Bacillus subtilis, will be described. PMID- 22064509 TI - 4'-(4-Chlorophenyl)-1'-methyldispiro[indan-2,2'-pyrrolidine-3',2''-indan]-1,3,1'' trione. AB - In the title compound, C(27)H(20)ClNO(3), the two cyclo-pentane rings adopt envelope conformations. The pyrrolidine ring also adopts an envelope conformation (with the spiro C atom as the flap) and its least-squares plane (fitted to five atoms) makes dihedral angles of 66.50 (9), 77.36 (8) and 73.76 (8) degrees with the chloro-benzene ring and the two 2,3-dihydro-1H-indene ring systems, respectively. The mol-ecular conformation is stabilized by an intra-molecular C H?O hydrogen bond, which generates an S(6) ring motif. In the crystal, mol-ecules are linked by C-H?O hydrogen bonds into chains running parallel to the [001] direction. PMID- 22064513 TI - Identification of isocitrate dehydrogenase 1 as a potential diagnostic and prognostic biomarker for non-small cell lung cancer by proteomic analysis. AB - Lung cancer is the leading cause of cancer-related death in the world. To explore tumor biomarkers for clinical application, two-dimensional fluorescence difference gel electrophoresis and subsequent MALDI-TOF/TOF mass spectrometry were performed to identify proteins differentially expressed in 12 pairs of lung squamous cell tumors and their corresponding normal tissues. A total of 28 nonredundant proteins were identified with significant alteration in lung tumors. The up-regulation of isocitrate dehydrogenase 1 (IDH1), superoxide dismutase 2, 14-3-3epsilon, and receptor of activated protein kinase C1 and the down regulation of peroxiredoxin 2 in tumors were validated by RT-PCR and Western blot analysis in independent 15 pairs of samples. Increased IDH1 expression was further verified by the immunohistochemical study in extended 73 squamous cell carcinoma and 64 adenocarcinoma clinical samples. A correlation between IDH1 expression and poor overall survival of non-small cell lung cancer (NSCLC) patients was observed. Furthermore, ELISA analysis showed that the plasma level of IDH1 was significantly elevated in NSCLC patients compared with benign lung disease patients and healthy individuals. In addition, knockdown of IDH1 by RNA interference suppressed the proliferation of NSCLC cell line and decreased the growth of xenograft tumors in vivo. These observations suggested that IDH1, as a protein promoting tumor growth, could be used as a plasma biomarker for diagnosis and a histochemical biomarker for prognosis prediction of NSCLC. PMID- 22064512 TI - Genetic contributions to behavioural diversity at the gene-environment interface. AB - Recent work on behavioural variation within and between species has furthered our understanding of the genetic architecture of behavioural traits, the identities of relevant genes and the ways in which genetic variants affect neuronal circuits to modify behaviour. Here we review our understanding of the genetics of natural behavioural variation in non-human animals and highlight the implications of these findings for human genetics. We suggest that gene-environment interactions are central to natural genetic variation in behaviour and that genes affecting neuromodulatory pathways and sensory processing are preferred sites of naturally occurring mutations. PMID- 22064514 TI - Performing custom microRNA microarray experiments. AB - microRNAs (miRNAs) are a large family of ~ 22 nucleotides (nt) long RNA molecules that are widely expressed in eukaryotes (1). Complex genomes encode at least hundreds of miRNAs, which primarily inhibit the expression of a vast number of target genes post-transcriptionally (2, 3). miRNAs control a broad range of biological processes (1). In addition, altered miRNA expression has been associated with human diseases such as cancers, and miRNAs may serve as biomarkers for diseases and prognosis (4, 5). It is important, therefore, to understand the expression and functions of miRNAs under many different conditions. Three major approaches have been employed to profile miRNA expression: real-time PCR, microarray, and deep sequencing. The technique of miRNA microarray has the advantage of being high-throughput, generally less expensive, and most of the experimental and analysis steps can be carried out in a molecular biology laboratory at most universities, medical schools and associated hospitals. Here, we describe a method for performing custom miRNA microarray experiments. A miRNA probe set will be printed on glass slides to produce miRNA microarrays. RNA is isolated using a method or reagent that preserves small RNA species, and then labeled with a fluorescence dye. As a control, reference DNA oligonucleotides corresponding to a subset of miRNAs are also labeled with a different fluorescence dye. The reference DNA will serve to demonstrate the quality of the slide and hybridization and will also be used for data normalization. The RNA and DNA are mixed and hybridized to a microarray slide containing probes for most of the miRNAs in the database. After washing, the slide is scanned to obtain images, and intensities of the individual spots quantified. These raw signals will be further processed and analyzed as the expression data of the corresponding miRNAs. Microarray slides can be stripped and regenerated to reduce the cost of microarrays and to enhance the consistency of microarray experiments. The same principles and procedures are applicable to other types of custom microarray experiments. PMID- 22064516 TI - Genetic selection for enhanced serine metabolism in cancer development. PMID- 22064517 TI - Nek9, Nek6, Nek7 and the separation of centrosomes. PMID- 22064518 TI - Targeted cancer therapy: what if the driver is just a messenger? AB - "Shoot the driver" is the paradigm of targeted cancer therapy. However, resistance to targeted inhibitors of signaling pathways is a major problem. In part the redundancy of signaling networks can bypass targeted inhibitors and thereby reduce their biological effect. In this case the driver turns out to be one of several potential messengers and is easily replaced. Cocktails of multiple targeted inhibitors are an obvious solution. This is limited, however, by the lack of potent inhibitors and may also produce increased toxicity. Therefore we explored the direct blockade of a key biological activity downstream from multiple converging oncogenic signals. Specifically, several oncogenic signaling pathways including AKT, MAPK and PIM kinase signals converge on the activation of cap-dependent translation. In cancer cells, aberrant activation of cap-dependent translation favors the increased expression of short-lived oncoproteins like c MYC, MCL1, CYCLIN D1 and the PIM kinases. Intriguingly, cancer cells are especially sensitive to even temporary reductions in these proteins. We will discuss our findings concerning translational inhibitor therapy in cancer. PMID- 22064519 TI - How CD95 stimulates invasion. AB - CD95 is best known for its capacity to induce apoptosis, but also activates multiple non-apoptotic signalling pathways. In particular, CD95 promotes migration and tissue invasion of apoptosis-resistant cell types, and this plays a central role in inflammation, neurobiology, and tumor biology. CD95 induces invasion by stimulating the expression of extracellular matrix (ECM)-degrading proteases, and by stimulating the formation of actin-driven cell protrusions through Rac and the cofilin pathway. In this review we discuss how CD95-initiated signalling pathways may cooperate to facilitate cell migration and tissue invasion. PMID- 22064520 TI - The role of mucin in GERD and its complications. AB - Acid, pepsin and other noxious material reach the esophageal mucosa and interact with the luminal aspect of the squamous epithelium. The first protective barrier to these potentially injurious substances is the mucus buffer layer that covers the mucosa. In healthy people, the esophagus has a protective surface adherent mucus gel barrier. Levels of mucin glycoprotein are considerably increased in response to acid and pepsin. A wide spectrum of mucin genes are expressed in normal esophageal mucosa, squamous cell carcinoma of the esophagus, Barrett epithelium and esophageal adenocarcinoma. The mucins MUC5AC and MUC6 are expressed to a similar degree in Barrett metaplasia and gastric mucosa, as is MUC2 in Barrett intestinal metaplasia and small bowel mucosa. Increased expression of MUC1 is associated with progression from dysplasia to adenocarcinoma of the esophagus. Thus, mucins have an important role in the defense of esophageal mucosa against the acid, pepsin and bile that are present in the refluxate. Changes in the expression of mucins occur in patients with GERD, and might lead to the development of new drugs. PMID- 22064521 TI - Crohn's disease: Cost-effectiveness of reducing radiation in Crohn's disease. PMID- 22064522 TI - Pancreas: Microglial activation key to pain in chronic pancreatitis. PMID- 22064523 TI - Metabolic syndrome: Cortisol production and the metabolic syndrome. PMID- 22064524 TI - New-generation vaccines against cholera. AB - Cholera is a major global health problem, causing approximately 100,000 deaths annually, about half of which occur in sub-Saharan Africa. Although early generation parenteral cholera vaccines were abandoned as public health tools owing to their limited efficacy, newer-generation oral cholera vaccines have attractive safety and protection profiles. Both killed and live oral vaccines have been licensed, although only killed oral vaccines are currently manufactured and available. These killed oral vaccines not only provide direct protection to vaccinated individuals, but also confer herd immunity. The combination of direct vaccine protection and vaccine herd immunity effects makes these vaccines highly cost-effective and, therefore, attractive for use in developing countries. Administration of these oral vaccines does not require qualified medical personnel, which makes their use practical--even in developing countries. Although new-generation oral cholera vaccines should not be considered in isolation from other preventive approaches, especially improved water quality and sanitation, they represent important tools in the public health armamentarium to control both endemic and epidemic cholera. PMID- 22064526 TI - Celiac disease: Lack of vitamins D and K affects bone health in celiac disease. PMID- 22064525 TI - IBD: a MAST3-regulated gene set in IBD. PMID- 22064527 TI - 4-Methyl-N-[(5-nitro-thio-phen-2-yl)methyl-idene]aniline. AB - The title compound, C(12)H(10)N(2)O(2)S, is a Schiff base formed from p-toluidine and 5-nitro-thio-phene-2-carbaldehyde. The C=N bond adopts an E configuration. The benzene and thio-phene rings form a dihedral angle of 9.2 (1) degrees . PMID- 22064528 TI - Directed HIV-1 evolution of protease inhibitor resistance by second-generation short hairpin RNAs. AB - Despite the success of antiretroviral drugs in decreasing AIDS-related mortality, a substantial fraction of HIV-infected patients experience therapy failure due to the emergence of drug-resistant virus variants. For durable inhibition of HIV-1 replication, the emergence of such escape viruses must be controlled. In addition to antiretroviral drugs, RNA interference (RNAi)-based gene therapy can be used to inhibit HIV-1 replication by targeting the viral RNA genome. RNAi is an evolutionary conserved gene silencing mechanism that mediates the sequence specific breakdown of the targeted mRNA. Here we investigated an alternative strategy combining the activity of a protease inhibitor (PI) with second generation short hairpin RNAs (shRNAs) designed to specifically block the emergence of PI-resistant HIV-1 variants. We demonstrate that dominant viral escape routes can be effectively blocked by second-generation shRNAs and that virus evolution can be redirected toward less-fit variants. These results are of importance for a deeper understanding of HIV-1 evolution under combined drug and RNAi pressure and may be used to design future therapeutic approaches. PMID- 22064529 TI - Low prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus isolates among Connecticut veterans. AB - The Etest glycopeptide resistance detection identified two potential heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) isolates from a screen of 288 methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients at a Connecticut Veterans Hospital. However, the two isolates did not meet the criteria for hVISA by the population analysis profile-area under the curve analysis, arguing against routine screening for hVISA in this low prevalence population. PMID- 22064530 TI - Zinc acetate/carrageenan gels exhibit potent activity in vivo against high-dose herpes simplex virus 2 vaginal and rectal challenge. AB - Topical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce the incidence of HIV infections worldwide. Previously we completed phase 3 testing of the carrageenan-based gel Carraguard. Although the trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex, it did show that Carraguard is safe when used weekly for up to 2 years. Moreover, Carraguard has in vitro activity against human papillomavirus (HPV) and HSV-2 and favorable physical and rheological properties, which makes it a useful vehicle to deliver antiviral agents such as zinc acetate. To that end, we previously reported that a prototype zinc acetate carrageenan gel protects macaques against vaginal challenge with combined simian-human immunodeficiency virus reverse transcriptase (SHIV-RT). Herein, we report the safety and efficacy of a series of zinc acetate and/or carrageenan gels. The gels protected mice (75 to 85% survival; P < 0.001) against high-dose (10(6)-PFU) HSV-2 vaginal or rectal challenge. In contrast, zinc acetate formulated in HEC (hydroxyethylcellulose; or the Universal Placebo) failed to protect mice against the high-dose vaginal HSV-2 challenge (similar to aqueous zinc acetate solution and the placebo controls). The gels were found to be effective spreading gels, exhibited limited toxicity in vitro, caused minimal damage to the architecture of the cervicovaginal and rectal mucosae in vivo, and induced no increased susceptibility to HSV-2 infection in a mouse model. Our results provide a strong rationale to further optimize and evaluate the zinc acetate/carrageenan gels for their ability to block the sexual transmission of HIV and HSV-2. PMID- 22064531 TI - Generic vancomycin enriches resistant subpopulations of Staphylococcus aureus after exposure in a neutropenic mouse thigh infection model. AB - Previous studies have shown that "bioequivalent" generic products of vancomycin are less effective in vivo against Staphylococcus aureus than the innovator compound. Considering that suboptimal bactericidal effect has been associated with emergence of resistance, we aimed to assess in vivo the impact of exposure to innovator and generic products of vancomycin on S. aureus susceptibility. A clinical methicillin-resistant S. aureus (MRSA) strain from a liver transplant patient with persistent bacteremia was used for which MIC, minimum bactericidal concentration (MBC), and autolytic properties were determined. Susceptibility was also assessed by determining a population analysis profile (PAP) with vancomycin concentrations from 0 to 5 mg/liter. ICR neutropenic mice were inoculated in each thigh with ~7.0 log(10) CFU. Treatment with the different vancomycin products (innovator and three generics; 1,200 mg/kg of body weight/day every 3 h) started 2 h later while the control group received sterile saline. After 24 h, mice were euthanized, and the thigh homogenates were plated. Recovered colonies were reinoculated to new groups of animals, and the exposure-recovery process was repeated until 12 cycles were completed. The evolution of resistance was assessed by PAP after cycles 5, 10, 11, and 12. The initial isolate displayed reduced autolysis and higher resistance frequencies than S. aureus ATCC 29213 but without vancomycin-intermediate S. aureus (VISA) subpopulations. After 12 cycles, innovator vancomycin had significantly reduced resistant subpopulations at 1, 2, and 3 mg/liter, while the generic products had enriched them progressively by orders of magnitude. The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide. PMID- 22064532 TI - Evolution of nasal carriage of methicillin-resistant coagulase-negative staphylococci in a remote population. AB - Nasal carriage of methicillin-resistant coagulase-negative staphylococci (MR CoNS) is highly prevalent in community subjects, but its dynamic has been little investigated. Nasal swabbing was performed in 2006 and 2008 in 154 Amerindians living isolated in French Guiana. MR-CoNS strains were identified and characterized by non-beta-lactam susceptibility testing and staphylococcal cassette chromosome mec element (SCCmec) typing, characterizing the associations of ccr and mec gene complex allotypes, and for MR Staphylococcus epidermidis (MRSE), multilocus variable number of tandem repeats analysis (MLVA) was used. The impact of sociodemographic and medical characteristics on the persistence of MR-CoNS carriage was assessed by bivariate analysis. Prevalence of MR-CoNS carriage was 50.6% in 2006 and 46.8% in 2008. The 274 MR-CoNS isolates, including S. epidermidis (n = 89, 62 MLVA patterns), Staphylococcus haemolyticus (n = 78), and Staphylococcus hominis (n = 72), exhibited 41 distinct ccr and mec gene complex associations. Persistent carriage (in 2006 and 2008), intermittent carriage (either in 2006 or 2008), and noncarriage were documented in 25.3, 47.4, and 27.3% of the participants, respectively. Persistent carriage of a given MRSE isolate was rarely observed (n = 8 isolates). Furthermore, no epidemiological factor, including antibiotic exposure, was associated with persistent carriage. The high diversity of MRSE clones and their ccr and mec gene complex associations contrasted with the high carriage rates in this isolated community, which might reflect the occurrence of SCCmec rearrangement and the generation of new MR-CoNS strains. PMID- 22064533 TI - Simulated antibiotic exposures in an in vitro hollow-fiber infection model influence toxin gene expression and production in community-associated methicillin-resistant Staphylococcus aureus strain MW2. AB - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain MW2 harbors a plethora of toxins to mediate its virulence. However, toxin expression and regulation with simulated clinical antimicrobial exposures are unclear. This study evaluated these relationships using an in vitro pharmacodynamic hollow-fiber infection model. Clinical doses of clindamycin, linezolid, minocycline, trimethoprim-sulfamethoxazole (SXT), and vancomycin were simulated over 72 h against MW2 in the hollow fiber model. Expression levels of lukSF-PV and enterotoxin genes sec4, sek, seq, and sel2 were quantified by real time PCR. Panton-Valentine leukocidin (PVL) was quantified by enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was determined on polymorphonuclear cells (PMNs). Vancomycin produced the maximum MW2 killing (2.53 log(10) CFU/ml) after the first dose, but the greatest sustained killing over 72 h occurred with linezolid and clindamycin. Vancomycin and minocycline induced gene upregulation from 0 to 8 h, followed by downregulation for the remaining simulation period. Clindamycin decreased gene expression in the first 24 h, followed by moderate increases (2.5-fold) thereafter. Linezolid increased gene expression 11.4- to 200.4-fold but inhibited PVL production (0.6 +/- 0.3 versus 5.9 +/- 0.2 MUg/ml, linezolid versus control at 72 h; P < 0.05). Similar effects on PVL production occurred with clindamycin and minocycline. SXT increased PVL production at 48 h (2.8-fold) and 72 h (4.9-fold) of treatment (P < 0.05), resulting in increased PVL cytotoxicity on PMNs. Linezolid, clindamycin, and minocycline were the most effective agents on decreasing the virulence potential in CA-MRSA, notably after 8 h of treatment. SXT had minimal effects on toxin gene regulation, but it increased production and cytotoxicity of PVL toxin in the model and may enhance virulence when it is used to treat severe infections. PMID- 22064534 TI - Galectin-1-specific inhibitors as a new class of compounds to treat HIV-1 infection. AB - Despite significant improvements, antiretroviral therapies against HIV-1 are plagued by a high frequency of therapeutic failures that have been associated with acquisition of drug resistance. We recently reported that HIV-1 exploits a host glycan binding protein, galectin-1, to increase its attachment to host cells, thereby increasing its overall infectivity in susceptible cells. This finding suggests that host molecules such as galectin-1 could reduce the expected efficiency of HIV-1 drugs targeting early steps of the replicative cycle, such as attachment and entry processes. Thus, new classes of drugs that would interfere with galectin-1/HIV-1 interactions could benefit the current antiretroviral therapy. To further explore this possibility, experiments were conducted to discover leading compounds showing specific inhibition of galectin-1 activity in a cellular model of HIV-1 infection. Three lactoside compounds were found to modestly inhibit the interaction of galectin-1 with primary human CD4(+) T cells. Interestingly, these same inhibitors reduced the galectin-1-mediated increase in HIV-1 attachment to target cells in a much more efficient manner. More important, the tested lactoside derivatives also significantly decreased the galectin-1 dependent enhancement of HIV-1 infection. These observations deserve further attention when considering that the development of new drugs to prevent and treat HIV-1 infection remains a priority. PMID- 22064535 TI - Virologic escape during danoprevir (ITMN-191/RG7227) monotherapy is hepatitis C virus subtype dependent and associated with R155K substitution. AB - Danoprevir is a hepatitis C virus (HCV) NS3/4A protease inhibitor that promotes multi-log(10) reductions in HCV RNA when administered as a 14-day monotherapy to patients with genotype 1 chronic HCV. Of these patients, 14/37 experienced a continuous decline in HCV RNA, 13/37 a plateau, and 10/37 a rebound. The rebound and continuous-decline groups experienced similar median declines in HCV RNA through day 7, but their results diverged notably at day 14. Plateau group patients experienced a lesser, but sustained, median HCV RNA decline. Baseline danoprevir susceptibility was similar across response groups but was reduced significantly at day 14 in the rebound group. Viral rebound in genotype 1b was uncommon (found in 2/23 patients). Population-based sequence analysis of NS3 and NS4A identified treatment-emergent substitutions at four amino acid positions in the protease domain of NS3 (positions 71, 155, 168, and 170), but only two (155 and 168) were in close proximity to the danoprevir binding site and carried substitutions that impacted danoprevir potency. R155K was the predominant route to reduced danoprevir susceptibility and was observed in virus isolated from all 10 rebound, 2/13 plateau, and 1/14 continuous-decline patients. Virus in one rebound patient additionally carried partial R155Q and D168E substitutions. Treatment-emergent substitutions in plateau patients were less frequently observed and more variable. Single-rebound patients carried virus with R155Q, D168V, or D168T. Clonal sequence analysis and drug susceptibility testing indicated that only a single patient displayed multiple resistance pathways. These data indicate the ascendant importance of R155K for viral escape during danoprevir treatment and may have implications for the clinical use of this agent. PMID- 22064536 TI - Distribution of spontaneous gyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in France. AB - We determined the prevalence of gyrA mutations conferring fluoroquinolone resistance in 97 Helicobacter pylori isolates collected in France from 2007 to 2010. Ninety-four harbored one or two mutations already found in the quinolone resistance determining region (QRDR) of gyrA (for T87I, n = 23; for N87K, n = 32; for D91N, n = 30; for D91G, n = 7; for D91Y, n = 6), 2 harbored a mutation never previously described (D91H and A88P), and one strain was resistant (ciprofloxacin MIC of 8 mg/liter) without a detected mutation conferring this resistance in gyrA or gyrB genes. PMID- 22064537 TI - The spiFEG locus in Streptococcus infantarius subsp. infantarius BAA-102 confers protection against nisin U. AB - Nisin U is a member of the extended nisin family of lantibiotics. Here we identify the presence of nisin U immunity gene homologues in Streptococcus infantarius subsp. infantarius BAA-102. Heterologous expression of these genes in Lactococcus lactis subsp. cremoris HP confers protection to nisin U and other members of the nisin family, thereby establishing that the recently identified phenomenon of resistance through immune mimicry also occurs with respect to nisin. PMID- 22064538 TI - In vivo comparison of CXA-101 (FR264205) with and without tazobactam versus piperacillin-tazobactam using human simulated exposures against phenotypically diverse gram-negative organisms. AB - CXA-101 is a novel antipseudomonal cephalosporin with enhanced activity against Gram-negative organisms displaying various resistance mechanisms. This study evaluates the efficacy of exposures approximating human percent free time above the MIC (%fT > MIC) of CXA-101 with or without tazobactam and piperacillin tazobactam (TZP) against target Gram-negative organisms, including those expressing extended-spectrum beta-lactamases (ESBLs). Sixteen clinical Gram negative isolates (6 Pseudomonas aeruginosa isolates [piperacillin-tazobactam MIC range, 8 to 64 MUg/ml], 4 Escherichia coli isolates (2 ESBL and 2 non-ESBL expressing), and 4 Klebsiella pneumoniae isolates (3 ESBL and 1 non-ESBL expressing) were used in an immunocompetent murine thigh infection model. After infection, groups of mice were administered doses of CXA-101 with or without tazobactam (2:1) designed to approximate the %fT > MIC observed in humans given 1 g of CXA-101 with or without tazobactam every 8 h as a 1-h infusion. As a comparison, groups of mice were administered piperacillin-tazobactam doses designed to approximate the %fT > MIC observed in humans given 4.5 g piperacillin tazobactam every 6 h as a 30-min infusion. Predicted piperacillin-tazobactam %fT > MIC exposures of greater than 40% resulted in static to >1 log decreases in CFU in non-ESBL-expressing organisms with MICs of <=32 MUg/ml after 24 h of therapy. Predicted CXA-101 with or without tazobactam %fT > MIC exposures of >=37.5% resulted in 1- to 3-log-unit decreases in CFU in non-ESBL-expressing organisms, with MICs of <=16 MUg/ml after 24 h of therapy. With regard to the ESBL expressing organisms, the inhibitor combinations showed enhanced CFU decreases versus CXA-101 alone. Due to enhanced in vitro potency and resultant increased in vivo exposure, CXA-101 produced statistically significant reductions in CFU in 9 isolates compared with piperacillin-tazobactam. The addition of tazobactam to CXA 101 produced significant reductions in CFU for 7 isolates compared with piperacillin-tazobactam. Overall, human simulated exposures of CXA-101 with or without tazobactam demonstrated improved efficacy versus piperacillin-tazobactam. PMID- 22064539 TI - In vitro phenotypic susceptibility of HIV-2 clinical isolates to CCR5 inhibitors. AB - HIV-2 is naturally resistant to nonnucleoside reverse transcriptase inhibitors, to a fusion inhibitor, and to some of the protease inhibitors. Maraviroc is the first drug of the new anti-CCR5 drug class and is effective only on CCR5-tropic (R5) HIV-1. No previous studies concerning HIV-2 susceptibility to maraviroc have been reported yet. We developed a phenotypic maraviroc susceptibility test using a peripheral blood mononuclear cell (PBMC) model. We analyzed the maraviroc susceptibility of 13 R5 HIV-2, 2 X4R5 (dual) HIV-2, and 2 CXCR4-tropic (X4) HIV-2 clinical isolates. We also tested, with the same protocol, 1 X4 HIV-1 and 4 R5 HIV-1 clinical isolates. For the R5 HIV-2 clinical isolates, the 50% effective concentration (EC(50)) for maraviroc was 0.80 nM (interquartile range [IQR], 0.48 to 1.39 nM), similar to that observed for the R5 HIV-1 isolates. The median maximum percentage of inhibition in the R5 HIV-2 isolates was 93% (IQR, 84 to 98%), similar to that observed in the R5 HIV-1 isolates. As expected, both X4 HIV 1 and HIV-2 were highly resistant to maraviroc. Our study showed for the first time that maraviroc is active in vitro against R5 HIV-2. The new tools we developed will allow identification of HIV-2-infected patients eligible for CCR5 inhibitor use and management of virological failure when receiving a maraviroc based regimen. PMID- 22064540 TI - Downregulation of mitogen-activated protein kinase 1 of Leishmania donovani field isolates is associated with antimony resistance. AB - Emergence of resistance to pentavalent antimonials has become a severe obstacle in the treatment of visceral leishmaniasis (VL) on the Indian subcontinent. The mechanisms operating in laboratory-generated strains are somewhat known, but the determinants of clinical antimony resistance are not well understood. By utilizing a DNA microarray expression profiling approach, we identified a gene encoding mitogen-activated protein kinase 1 (MAPK1) for the kinetoplast protozoan Leishmania donovani (LdMAPK1) that was consistently downregulated in antimony resistant field isolates. The expression level of the gene was validated by real time PCR. Furthermore, decreased expression of LdMAPK1 was also confirmed at the protein level in resistant isolates. Primary structure analysis of LdMAPK1 revealed the presence of all of the characteristic features of MAPK1. When expressed in Escherichia coli, the recombinant enzyme showed kinase activity with myelin basic protein as the substrate and was inhibited by staurosporine. Interestingly, overexpression of this gene in a drug-sensitive laboratory strain and a resistant field isolate resulted in increased the sensitivity of the transfectants to potassium antimony tartrate, suggesting that it has a role in antimony resistance. Our results demonstrate that downregulation of LdMAPK1 may be in part correlated with antimony drug resistance in Indian VL isolates. PMID- 22064541 TI - The oligo-acyl lysyl antimicrobial peptide C12K-2beta12 exhibits a dual mechanism of action and demonstrates strong in vivo efficacy against Helicobacter pylori. AB - Helicobacter pylori has developed antimicrobial resistance to virtually all current antibiotics. Thus, there is a pressing need to develop new anti-H. pylori therapies. We recently described a novel oligo-acyl-lysyl (OAK) antimicrobial peptidomimetic, C(12)K-2beta(12), that shows potent in vitro bactericidal activity against H. pylori. Herein, we define the mechanism of action and evaluate the in vivo efficacy of C(12)K-2beta(12) against H. pylori after experimental infection of Mongolian gerbils. We demonstrate using a 1-N phenylnaphthylamine (fluorescent probe) uptake assay and electron microscopy that C(12)K-2beta(12) rapidly permeabilizes the bacterial membrane and creates pores that cause bacterial cell lysis. Furthermore, using nucleic acid binding assays, Western blots, and confocal microscopy, we show that C(12)K-2beta(12) can cross the bacterial membranes into the cytoplasm and tightly bind to bacterial DNA, RNA, and proteins, a property that may result in inhibition of enzymatic activities and macromolecule synthesis. To define the in vivo efficacy of C(12)K 2beta(12), H. pylori-infected gerbils were orogastrically treated with increasing doses and concentrations of C(12)K-2beta(12) 1 day or 1 week postinfection. The efficacy of C(12)K-2beta(12) was strongest in animals that received the largest number of doses at the highest concentration, indicating dose-dependent activity of the peptide (P < 0.001 by analysis of variance [ANOVA]) regardless of the timing of the treatment with C(12)K-2beta(12). Overall, our results demonstrate a dual mode of action of C(12)K-2beta(12) against the H. pylori membrane and cytoplasmic components. Moreover, and consistent with the previously reported in vitro efficacy, C(12)K-2beta(12) shows significant in vivo efficacy against H. pylori when used as monotherapy. Therefore, OAK peptides may be a valuable resource for therapeutic treatment of H. pylori infection. PMID- 22064542 TI - Differential effects of linezolid and ciprofloxacin on toxin production by Bacillus anthracis in an in vitro pharmacodynamic system. AB - Bacillus anthracis causes anthrax. Ciprofloxacin is a gold standard for the treatment of anthrax. Previously, using the non-toxin-producing DeltaSterne strain of B. anthracis, we demonstrated that linezolid was equivalent to ciprofloxacin for reducing the total (vegetative and spore) bacterial population. With ciprofloxacin therapy, the total population consisted of spores. With linezolid therapy, the population consisted primarily of vegetative bacteria. Linezolid is a protein synthesis inhibitor, while ciprofloxacin is not. Since toxins are produced only by vegetative B. anthracis, the effect of linezolid and ciprofloxacin on toxin production is of interest. The effect of simulated clinical regimens of ciprofloxacin and linezolid on the vegetative and spore populations and on toxin production was examined in an in vitro pharmacodynamic model over 15 days by using the toxin-producing Sterne strain of B. anthracis. Ciprofloxacin and linezolid reduced the total Sterne population at similar rates. With ciprofloxacin therapy, the total Sterne population consisted of spores. With linezolid therapy, >90% of the population was vegetative B. anthracis. With ciprofloxacin therapy, toxin was first detectable at 3 h and remained detectable for at least 5 h. Toxin was never detected with linezolid therapy. Ciprofloxacin and linezolid reduced the total Sterne population at similar rates. However, the B. anthracis population was primarily spores with ciprofloxacin therapy and was primarily vegetative bacteria with linezolid therapy. Toxin production was detected for at least 5 h with ciprofloxacin therapy but was never detected with linezolid treatment. Linezolid may have an advantage over ciprofloxacin for the treatment of B. anthracis infections. PMID- 22064543 TI - Discovery and engineered overproduction of antimicrobial nucleoside antibiotic A201A from the deep-sea marine actinomycete Marinactinospora thermotolerans SCSIO 00652. AB - Marinactinospora thermotolerans SCSIO 00652, originating from a deep-sea marine sediment of the South China Sea, was discovered to produce antimicrobial nucleoside antibiotic A201A. Whole-genome scanning and annotation strategies enabled us to localize the genes responsible for A201A biosynthesis and to experimentally identify the gene cluster; inactivation of mtdF, an oxidoreductase gene within the suspected gene cluster, abolished A201A production. Bioinformatics analysis revealed that a gene designated mtdA furthest upstream within the A201A biosynthetic gene cluster encodes a GntR family transcriptional regulator. To determine the role of MtdA in regulating A201A production, the mtdA gene was inactivated in frame and the resulting DeltamtdA mutant was fermented alongside the wild-type strain as a control. High-performance liquid chromatography (HPLC) analyses of fermentation extracts revealed that the DeltamtdA mutant produced A201A in a yield ~25-fold superior to that of the wild type strain, thereby demonstrating that MtdA is a negative transcriptional regulator governing A201A biosynthesis. By virtue of its high production capacity, the DeltamtdA mutant constitutes an ideal host for the efficient large scale production of A201A. These results validate M. thermotolerans as an emerging source of antibacterial agents and highlight the efficiency of metabolic engineering for antibiotic titer improvement. PMID- 22064544 TI - Evaluation of ceftobiprole activity against a variety of gram-negative pathogens, including Escherichia coli, Haemophilus influenzae (beta-lactamase positive and beta-lactamase negative), and Klebsiella pneumoniae, in a rabbit meningitis model. AB - Ceftobiprole medocaril, a new cephalosporin, is highly active against a broad spectrum of Gram-positive and Gram-negative clinical pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant pneumococci. In this study, we tested ceftobiprole against various Gram-negative pathogens in a rabbit meningitis model and determined its penetration into the cerebrospinal fluid (CSF). In this animal model, ceftobiprole produced an antibacterial activity similar to that of cefepime against an Escherichia coli strain, a Klebsiella pneumoniae strain, and a beta-lactamase-negative Haemophilus influenzae strain. Against a beta-lactamase-positive H. influenzae strain, ceftobiprole was significantly superior. The penetration of ceftobiprole through inflamed meninges reached about 16% of serum levels compared to about 2% of serum levels through uninflamed meninges. PMID- 22064545 TI - Population pharmacokinetics of voriconazole in adults. AB - Voriconazole is a first-line agent for the treatment of invasive fungal infections. The pharmacology of voriconazole is characterized by extensive interindividual variability and nonlinear pharmacokinetics. The population pharmacokinetics of voriconazole in 64 adults is described. The patient population consisted of 21 healthy volunteers, who received a range of intravenous (i.v.) and oral voriconazole regimens, and 43 patients with proven or probable invasive aspergillosis, who received the currently licensed dosage. Voriconazole concentrations were measured using high-performance liquid chromatography (HPLC). The pharmacokinetic data were modeled using a nonparametric methodology and with a nonlinear pharmacokinetic structural model. The extent and consequences of pharmacokinetic variability were explored using Monte Carlo simulation. The relationship between drug exposure and clinical response was explored using logistic regression. Optimal sampling times were identified using D-optimal design. The fit of the nonlinear model was acceptable. Data from the healthy volunteers provided robust estimates for K(m) and the maximum rate of enzyme activity (V(max)). The Bayesian parameter estimates were more variable and statistically different in patients than in volunteers. There was a linear relationship between the trough concentration and area under the concentration-time curve (AUC(0-12)). There was no relationship between the AUC(0 12) and clinical response. The original parameter values were readily recapitulated using Monte Carlo simulation. Initial i.v. dosing resulted in higher AUC(0-12) and trough concentrations compared with oral dosing. Sample collection times of 1, 2, 3, 4, 8, and 12 h after an i.v. infusion are maximally informative times for future pharmacokinetic studies. PMID- 22064546 TI - Pharmacodynamic effects of simulated standard doses of antifungal drugs against Aspergillus species in a new in vitro pharmacokinetic/pharmacodynamic model. AB - In conventional MUIotaC tests, fungi are exposed to constant drug concentrations, whereas in vivo, fungi are exposed to changing drug concentrations. Therefore, we developed a new in vitro pharmacokinetic/pharmacodynamic model where human plasma pharmacokinetics of standard doses of 1 mg/kg amphotericin B, 4 mg/kg voriconazole, and 1 mg/kg caspofungin were simulated and their pharmacodynamic characteristics were determined against three clinical isolates of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus with identical MICs (1 mg/liter for amphotericin B, 0.5 mg/liter for voriconazole) and minimum effective concentrations (0.5 mg/liter for caspofungin). This new model consists of an internal compartment (a 10-ml dialysis tube made out of a semipermeable cellulose membrane allowing the free diffusion of antifungals but not galactomannan) inoculated with Aspergillus conidia and placed inside an external compartment (a 700-ml glass beaker) whose content is diluted after the addition of antifungal drugs by a peristaltic pump at the same rate as the clearance of the antifungal drugs in human plasma. Fungal growth was assessed by galactomannan production. Despite demonstrating the same MICs, amphotericin B completely inhibited (100%) A. fumigatus but not A. flavus and A. terreus, whose growth was delayed for 7.53 and 22.8 h, respectively. Voriconazole partially inhibited A. fumigatus (49.5%) and Alpha. flavus (27.9%) but not Alpha. terreus; it delayed their growth by 3.99 h (A. fumigatus) and 5.37 h (Alpha. terreus). Caspofungin did not alter galactomannan production in all of the species but A. terreus. The new model simulated human pharmacokinetics of antifungal drugs and revealed important pharmacodynamic differences in their activity. PMID- 22064548 TI - PCP goes organic. PMID- 22064549 TI - Cell polarity: The missing link in skeletal morphogenesis? AB - Despite extensive genetic analysis of the dynamic multi-phase process that transforms a small population of lateral plate mesoderm into the mature limb skeleton, the mechanisms by which signaling pathways regulate cellular behaviors to generate morphogenetic forces are not known. Recently, a series of papers have offered the intriguing possibility that regulated cell polarity fine-tunes the morphogenetic process via orienting cell axes, division planes and cell movements. Wnt5a-mediated non-canonical signaling, which may include planar cell polarity, has emerged as a common thread in the otherwise distinct signaling networks that regulate morphogenesis in each phase of limb development. These findings position the limb as a key model to elucidate how global tissue patterning pathways direct local differences in cell behavior that, in turn, generate growth and form. PMID- 22064550 TI - Detection and localization of active gastrointestinal bleeding with multidetector row computed tomography angiography: a 5-year prospective study in one medical center. AB - GOAL: To prospectively assess the utility of multidetector row computed tomography angiography (MDCTA) in the diagnosis of active gastrointestinal bleeding (GIB). BACKGROUND: MDCTA is a relatively recent advance in CT scanning technology enabling excellent vascular visualization and detection of various vascular abnormalities. However, there is no prospective study with a large population evaluating the role of MDCTA in the diagnosis of active GIB. STUDY: From January 2006 to January 2011, 113 consecutive patients with clinical signs of active GIB underwent MDCTA (16-slice, 64-slice, or dual-source). The criteria for positive CT findings included active extravasation of contrast material within bowel lumen, abnormal bowel mucosal enhancement, vascular malformation, abnormally enhancing polyp or diverticulum, or tumor. Two radiologists reviewed the images and assessed CT findings in consensus. The standards of reference included digital subtraction angiography, endoscopy, surgery, or final pathology reports. Sensitivity, specificity, positive and negative predictive values, and accuracy of MDCTA for detection of active GIB were evaluated. RESULTS: Positive CT findings for active GIB were identified in 80 of 113 patients (70.8%), all of which were confirmed by 1 or more reference standard. Negative MDCTA results were obtained in 33 patients (29.2%). Of these, 27 patients did not require any further intervention and were discharged without incident. The overall sensitivity, specificity, positive and negative predictive values, and accuracy of MDCTA was 86.0%, 100%, 100%, 60.6%, and 88.5%, respectively. CONCLUSIONS: MDCTA is an accurate first-line screening method for detection and localization of GIB and can guide triage in patients with active GIB. PMID- 22064551 TI - Can percutaneous cholecystostomy be a definitive management for both acute calculous and acalculous cholecystitis? PMID- 22064552 TI - Endoscopic ampullectomy: techniques and outcomes. AB - Advances in endoscopic ampullectomy continue to mitigate concerns regarding incomplete removal of ampullary neoplasias, postprocedure complications, and insufficient treatment of tumors with undetected malignant foci or intraductal invasion. Advanced T staging of these lesions with endoscopic ultrasound and intraductal ultrasound, while useful tools for selection of candidates for snare polypectomy, should be limited to lesions either greater than 3 cm, bearing the macroscopic appearance of malignancy or unamenable to endoscopic therapy. Intraductal ultrasound has demonstrated T-staging accuracy superior to endoscopic ultrasound. One prospective study of prophylactic pancreatic stent placement and a number of retrospective studies have reported reduced complication rates. Recent studies continue to propose follow-up endoscopic retrograde cholangiopancreatography at 3-month intervals after ampullectomy to evaluate for recurrence and ablate residual tissue, with the interval increased to 6 to 12 months for 5 years on obtaining negative biopsies for adenomatous tissue. The development of thermal ablation, notably argon plasma coagulation, for fulguration of residual unresectable tumor, biductal sphincterotomy and prophylactic pancreatic pancreatic stent placement, and advanced diagnostic imaging mitigate the concerns leveled against endoscopic ampullectomy. In experienced hands, endoscopic papillectomy of noninvasive, benign ampullary lesions is a safe, technically feasible, and effective alternative to surgical resection. This study will focus on diagnosis and staging of ampullary adenomas and reviews indications for, and outcomes and complications of, endoscopic papillectomy. PMID- 22064553 TI - Same-day bowel cleansing regimen is superior to a split-dose regimen over 2 days for afternoon colonoscopy: results from a large prospective series. AB - GOALS AND BACKGROUND: Conventional bowel preparation for afternoon colonoscopy requires an oral agent the day before the procedure. Bowel cleansing given only on the day of the colonoscopy has never been attempted. The aims of this study were to compare the efficacy of bowel cleansing, impact on activities of daily living (ADLs), side effects, and patient preference of a same-day regimen with a 2-day regimen. STUDY: A single-blinded, prospective cohort study. Patients were block recruited into 2 groups with the endoscopist blinded to the regimen. Group A: 3 sachets of sodium picosulphate given at 12:00 noon and at 05:00 PM the day before and at 8:00 AM on the morning of the procedure. Group B: 2 sachets of sodium picosulphate on the morning of the procedure at 07:00 and 10:00 AM. Patients completed a quality-of-life questionnaire investigating the side effects, impact on ADLs, and regimen preference. The main outcome measures were mucosal cleansing, impact on ADLs, side effects, and patient preference of the regimen. RESULTS: A total of 227 patients underwent screening colonoscopy. There were 95 patients in group A and 132 in group B, all of whom were age and sex matched. Same-day preparation produced better mucosal cleansing (P = 0.0046) with fewer side effects (P = 0.002). Impact on ADLs was less with the same-day regimen (P < 0.0001). Significantly more number of patients preferred the same-day preparation compared with the 2-day regimen (P = 0.0147). CONCLUSIONS: Same-day bowel preparation is feasible, safe, and more effective than a split-dose regimen. It has fewer adverse events and is preferred by patients. PMID- 22064554 TI - HER-2/neu overexpression is an independent prognostic factor for intestinal-type and early-stage gastric cancer patients. AB - GOALS: To evaluate the HER-2/neu protein level by immunohistochemistry (IHC) and its gene amplification by fluorescence in situ hybridization (FISH) in gastric cancer samples, and the relevance to the prognosis of gastric cancer patients. STUDY: HER-2/neu overexpression and gene amplification were examined with semiquantitative standardized IHC in 775 formalin-fixed paraffin-embedded gastric cancer samples, and 252 of these cases were analyzed with FISH. RESULTS: Of the 775 gastric cancer samples examined by IHC, a total of 88 (11%) cases were positive for HER-2/neu overexpression at a score of 3+; another 44 (6%) cases were equivocal with a score of 2+; and the rest 643 (83%) cases were negative scored as 0/1+. Intestinal-type and early-stage cancers exhibited higher rate of HER-2/neu overexpression than those of diffuse/mixed-type and advanced cancers (P<0.05). Intestinal-type and early-stage cancers with HER-2/neu overexpression also exhibited short 5 year survival rates (21% vs. 47%, P=0.027; 29% vs. 60%, P=0.037) than HER-2/neu-negative cases, but not in the diffuse/mixed-type and advanced stage cancers. By FISH analysis, it was shown that 70% (60/86) of IHC 3+ had HER-2/neu gene amplication. In contrast, only 14% (6/43) of IHC 2+ cases, and 2.5% (3) of the 120 cases with IHC 0/1+ randomly selected showed HER-2/neu gene amplification. CONCLUSIONS: HER-2/neu overexpression may be used as an independent prognostic factor for intestinal-type and early-stage gastric cancer patients. IHC 3+ and 2+ cases should be further detected by FISH to assess HER 2/neu gene status. Patients with HER-2/neu amplification also might constitute potential candidates for targeted therapy with trastuzumab. PMID- 22064555 TI - Utility of soluble angiogenic factors as biomarker for disease severity and prognosis. PMID- 22064556 TI - The intestinal microbiota and obesity. AB - Obesity has been and continues to be an epidemic in the United States. Obesity has been addressed in multiple health initiatives, including Healthy People 2010, with no state meeting the proposed goal of a prevalence of obesity < 15% of the adult population. In contrast, obesity rates have continued to increase, with the self-reported prevalence of obesity among adults increasing by 1.1% from 2007 to the present. Indeed, since 2009, 33 states reported obesity prevalences of 25% or more with only 1 state reporting prevalence < 20%. There have been multiple approaches for the treatment of obesity, including fad diets, incentive-based exercise programs, and gastric bypass surgery; none of which have been optimal. In a murine model, it was shown that the majority of the intestinal microbiome consists of two bacterial phyla, the Bacteroidetes and the Firmicutes, and that the relative abundance of these two phyla differs among lean and obese mice; the obese mouse had a higher proportion of Firmicutes to Bacteroidetes (50% greater) than the lean mouse. The same results were appreciated in obese humans compared to lean subjects. The postulated explanation for this finding is that Firmicutes produce more complete metabolism of a given energy source than do Bacteroidetes, thus promoting more efficient absorption of calories and subsequent weight gain. Researchers were able to demonstrate that colonizing germ-free mice with the intestinal microbiome from obese mice led to an increased total body fat in the recipient mice despite a lack of change in diet. The converse, that, colonizing germ-free obese mice with the intestinal microbiome of thin mice causing a decreased total body fat in the recipient mice, has not yet been done. Other possible mechanisms by which the intestinal microbiome affects host obesity include induction of low-grade inflammation with lipopolysaccharide, regulation of host genes responsible for energy expenditure and storage, and hormonal communication between the intestinal microbiome and the host. The following review discusses the microbiome-obesity relationship and proposed mechanisms by which the intestinal microbiota is hypothesized to influence weight gain. PMID- 22064557 TI - False-positive tissue transglutaminase antibody levels occur in HIV-positive patients: HLA typing is essential. PMID- 22064558 TI - rac-8a'-Methyl-3',4',8',8a'-tetra-hydro-2'H-spiro-[[1,3]dioxolane-2,1' naphthalen]-6'(7'H)-one. AB - The title racemic compound, C(13)H(18)O(3), a common precursor in the total synthesis of terpenes, crystallizes with two molecules in the asymmetric unit. The crystal structure is made up of triple chains, formed by weak inter-molecular C-H?O contacts, propagating in the a-axis direction. PMID- 22064559 TI - Bacterial physiology. Stressed bacteria aren't lost without a leader. PMID- 22064560 TI - Extreme genome reduction in symbiotic bacteria. AB - Since 2006, numerous cases of bacterial symbionts with extraordinarily small genomes have been reported. These organisms represent independent lineages from diverse bacterial groups. They have diminutive gene sets that rival some mitochondria and chloroplasts in terms of gene numbers and lack genes that are considered to be essential in other bacteria. These symbionts have numerous features in common, such as extraordinarily fast protein evolution and a high abundance of chaperones. Together, these features point to highly degenerate genomes that retain only the most essential functions, often including a considerable fraction of genes that serve the hosts. These discoveries have implications for the concept of minimal genomes, the origins of cellular organelles, and studies of symbiosis and host-associated microbiota. PMID- 22064562 TI - A history of hookworm vaccine development. AB - The human hookworms Necator americanus and Ancylostoma duodenale remain among the most common infections of humans in areas of rural poverty in the developing regions of the world, with an estimated 1 billion people infected with one or more of these parasites. Herein, we review the nearly 100 years of research, development, animal testing, and fieldwork that have led to our current progress in recombinant hookworm vaccines. We begin with the identification of hookworm at the start of the 20th century in Southern US, then discuss the progress in developed countries to eliminate human hookworm infection, and then the industrial development and field use in the 1970s a canine hookworm vaccine(Ancylostoma caninum), and finally our progress to date in the development and clinical testing of an array of recombinant antigens to prevent human hookworm disease from N. americanus infection. Special attention is given to the challenges faced in the development of a vaccine against a blood-feeding nematode, including the epidemiology of infection (high prevalence of infection), pathogenesis (chronic infection that increases with the age of the host), and a robust immune response that fails to confer the protection in the host and a concomitant absence of correlates of protection by a successful vaccine could be developed and tested. Finally, we provide the optimal and acceptable profiles of a human hookworm vaccine, including the proposed indication, target population, and route of administration, as developed by the Human Hookworm Vaccine Initiative, the only group currently working on vaccines targeting this parasite. PMID- 22064563 TI - Medication utilization for targeted symptoms in children and adults with fragile X syndrome: US survey. AB - OBJECTIVE: To identify the most common neurological and behavioral symptoms treated by medications in individuals with fragile X syndrome (FXS), factors associated with treatment variability, and difficulty in swallowing a pill. METHOD: A total of 1019 caregivers provided information about 1064 sons and 299 daughters with FXS in a US national survey. Caregivers reported (a) current use of medications for attention, anxiety, hyperactivity, mood swings, anger, depression, seizures, self-injury, or sleep; (b) perceived efficacy; and (c) difficulty in swallowing a pill. RESULTS: Sixty-one percent of males and 38% of females were currently taking medication for at least 1 symptom. The most common symptoms were anxiety, attention, and hyperactivity. Treatments for attention and hyperactivity were common in childhood but declined substantially after the age of 18 years; anxiety treatment remained high in adults. Children perceived to be more impaired and children diagnosed or treated for autism were more likely to be taking medications. Caregivers considered most medications somewhat effective, but less than one-third rated current medication as "a lot" effective. Many children had difficulty swallowing a pill, but only 11% of adult males and 2% of adult females had a lot of difficulty. CONCLUSION: Symptom-based medication use is common in FXS, although response is incomplete and there is clearly an unmet need for medications with improved efficacy. The persistent use of medications to treat anxiety, mood, and behavior problems throughout adolescence and into the adult years suggests important outcomes when evaluating the efficacy of new medications. PMID- 22064572 TI - 1-Methyl-3-(4-chloro-benzo-yl)imidazo[1,2-a]pyridin-1-ium-2-olate. AB - In the mol-ecule of the title compound, C(15)H(11)ClN(2)O(2), the nine-membered heterobicycle is approximately planar [largest deviation from least-squares plane = 0.012 (2) A] and forms a dihedral angle of 51.14 (8) degrees with the plane of the 4-chloro-phenyl group. There is a non-classical intra-molecular hydrogen bond between the pyridine alpha-H atom and the O atom of the benzoyl group. The crystal structure is stabilized by weak C-H?O and C-H?Cl inter-actions involving the 'olate' O atom and the Cl atom attached to the benzoyl group as acceptors. PMID- 22064573 TI - 3-Ferrocenyl-2-(4-nitro-phen-yl)acrylonitrile. AB - In the title compound, [Fe(C(5)H(5))(C(14)H(9)N(2)O(2))], the ferrocenyl rings exhibit an eclipsed conformation with a staggering angle of 15.9 degrees , which is quite large compared to similar compounds. PMID- 22064575 TI - QTc prolongation in the intensive care unit: a review of offending agents. PMID- 22064577 TI - Patient- and family-centered care in the neonatal intensive care unit in our own words: one family's story. PMID- 22064578 TI - Nutritional supplements in critical illness. AB - Poor nutritional intake during critical illness can contribute to increased morbidity and mortality. Although nutrition strategies for critically ill patients attempt to provide essential macronutrients, recent evidence suggests that certain micronutrients and supplements may improve wound healing and decrease infectious and inflammatory complications. This review will focus on mechanism of action, adverse effects and drug interactions reported in the literature, and appropriate dosing and outcomes data for specific nutritional supplements in various critically ill adult populations. PMID- 22064580 TI - Caring for the critically ill patient with cancer. PMID- 22064581 TI - Advances in oncology care: targeted therapies. AB - The start of the 21st century has produced advances in cancer care that have improved both survival rates and quality of life for many persons diagnosed with cancer. Targeted therapy has given new hope for controlling cancer as a chronic illness. Alone, or in combination with traditional therapies such as surgery, radiation, and/or chemotherapy, this new form of therapy targets malignant cells, halting tumor growth and the potential metastatic spread of disease. Toxicities are limited, but some are serious and may require intensive care. It is imperative for the experienced critical care nurse to have an understanding of these new treatment options and those on the horizon, as these therapies are the future of cancer care. Whereas in previous decades, patients with cancer may not have survived an intensive care admission for treatment complications or advanced disease, many patients now are recovering from life-threatening events, continuing treatment for their disease, and going on to live meaningful, good quality lives. PMID- 22064583 TI - Oncologic emergencies: new decade, new perspectives. AB - The picture of oncologic emergencies in the intensive care unit has changed over the past decade. The classic emergencies, that is, superior vena cava syndrome, spinal cord compression, tumor lysis syndrome and life-threatening hypercalcemia, are now routinely managed on the general oncology unit or in an outpatient setting. Vigilant monitoring for early signs of complications, proactive interventions to prevent complications, and aggressive management account for this change. Currently, emergent conditions that necessitate intensive care unit admission or transfer in the patient with cancer include respiratory failure, cardiac emergencies, hemorrhagic events and coagulopathies, sepsis, and hemodynamic instability. This article will present the current evidence-based management of these conditions, a brief summary of classic oncologic emergencies, and the role of the critical care nurse in meeting the multidimensional needs of the patient and family during the life-threatening episode, based on Ferrell's quality of life model. PMID- 22064584 TI - Aggressive disease, aggressive treatment: the adult hematopoietic stem cell transplant patient in the intensive care unit. AB - Hematopoietic stem cell transplant is associated with high morbidity and mortality. Transplant is often the only curative therapy for cancers such as leukemia, lymphoma, and multiple myeloma. Between 40% and 80% of patients who receive transplant become long-term survivors, and intensive care unit (ICU) admission rates are between 24% and 44% during the peritransplant period. The aggressive nature of hematopoietic stem cell transplant has a drastic impact on the physical and emotional state of the patient and family. From the day of diagnosis of any blood cancer, patients and families are faced with decisions and challenges ranging from quality of life and mortality to insurance coverage and financial concerns. The purpose of this article is to provide the experienced ICU nurse with background on the hematopoietic stem cell transplant process as a basis for interventions that can improve patient- and family-centered care, to provide tools that improve the transitions between the transplant and ICU teams, and to support communication between nursing teams for patients who survive the ICU stay and for those at the end of life. Collaboration between 2 separate nursing units can result in exceptional care for this complex patient population. PMID- 22064585 TI - Managing cancer-related pain in critical care settings. AB - Pain is a common symptom experienced by individuals who are in treatment for cancer and becomes more prevalent for those with more advanced stages of malignancy. Critical care nurses are essential in the management of cancer related pain, which is a challenging problem when individuals who have a cancer diagnosis are admitted to the intensive care unit for emergent conditions. Regular, thorough, and patient-appropriate assessments by experienced critical care nurses guide selection of treatment modalities, including pharmacologic and nonpharmacologic techniques. In addition, existential pain necessitates spiritual care intervention, and involvement of other appropriate interdisciplinary team members can result in improved management of all types of pain experienced by critically ill individuals with cancer. PMID- 22064586 TI - Providing a "good death" for oncology patients during the final hours of life in the intensive care unit. AB - Cancer is a leading cause of death in the United States. Aggressiveness of cancer care continues to rise in parallel with scientific discoveries in the treatment of a variety of malignancies. As a result, patients with cancer often require care in intensive care units (ICUs). Although growth in hospice and palliative care programs has occurred nationwide, access to these programs varies by geographic region and hospital type. Thus, critical care nurses may be caring for patients with cancer during the final hours of life in the ICU without the support of palliative care experts. This article provides an overview of the meaning of the final hours of life for cancer patients and uses principles of a "good death" and the tenets of hospice care to organize recommendations for critical care nurses for providing high quality end-of-life care to patients with cancer in the ICU. PMID- 22064587 TI - The meaning of our work: caring for the critically ill patient with cancer. AB - The prevalence and survival rates of critically ill patients with cancer in the intensive care unit have increased considerably in the past 2 decades; yet, the meaning of caring for cancer patients in this setting may fall along a continuum. This article addresses the nurse's experience in caring for the critically ill patient with cancer by presenting a current profile of these patient in the intensive care unit in the context of the historical development and mission of critical care and the evolution of cancer as a chronic disease. The moral distress that can result when these 2 "cultures" or "realities" collide and the meaning of the nurse's work will be examined. Strategies and resources for critical care nurses to incorporate into their practice when caring for the critically ill patient with cancer, and themselves, will be addressed. PMID- 22064589 TI - When and how to evaluate interrater reliability of patient assessment tools. PMID- 22064590 TI - Monitor alarms and alarm fatigue. PMID- 22064591 TI - Prevalence and significance of alterations in cardiac structure and function in patients with heart failure and a preserved ejection fraction. AB - BACKGROUND: The purpose of this study was to examine the prevalence of abnormalities in cardiac structure and function present in patients with heart failure and a preserved ejection fraction (HFPEF) and to determine whether these alterations in structure and function were associated with cardiovascular morbidity and mortality. METHODS AND RESULTS: The Irbesartan in HFPEF trial (I PRESERVE) enrolled 4128 patients; echocardiographic determination of left ventricular (LV) volume, mass, left atrial (LA) size, systolic function, and diastolic function were made at baseline in 745 patients. The primary end point was death or protocol-specific cardiovascular hospitalization. A secondary end point was the composite of heart failure death or heart failure hospitalization. Associations between baseline structure and function and patient outcomes were examined using univariate and multivariable Cox proportional hazard analyses. In this substudy, LV hypertrophy or concentric remodeling was present in 59%, LA enlargement was present in 66%, and diastolic dysfunction was present in 69% of the patients. Multivariable analyses controlling for 7 clinical variables (including log N-terminal pro-B-type natriuretic peptide) indicated that increased LV mass, mass/volume ratio, and LA size were independently associated with an increased risk of both primary and heart failure events (all P<0.05). CONCLUSIONS: Left ventricular hypertrophy or concentric remodeling, LA enlargement, and diastolic dysfunction were present in the majority of patients with HFPEF. Left ventricular mass and LA size were independently associated with an increased risk of morbidity and mortality. The presence of structural remodeling and diastolic dysfunction may be useful additions to diagnostic criteria and provide important prognostic insights in patients with HFPEF. PMID- 22064592 TI - Benefit of transferring ST-segment-elevation myocardial infarction patients for percutaneous coronary intervention compared with administration of onsite fibrinolytic declines as delays increase. AB - BACKGROUND: Although randomized trials suggest that transfer for primary percutaneous coronary intervention (X-PCI) in ST-segment-elevation myocardial infarction is superior to onsite fibrinolytic therapy (O-FT), the generalizability of these findings to routine clinical practice is unclear because door-to-balloon (XDB) times are rapid in randomized trials but are frequently prolonged in practice. We hypothesized that delays resulting from transfer would reduce the survival advantage of X-PCI compared with O-FT. METHODS AND RESULTS: ST-segment-elevation myocardial infarction patients enrolled in the National Registry of Myocardial Infarction (NRMI) within 12 hours of pain onset were identified. Propensity matching of patients treated with X-PCI and O-FT was performed, and the effect of PCI-related delay on in-hospital mortality was assessed. PCI-related delay was calculated by subtracting the XDB from the door to-needle time in each matched pair. Conditional logistic regression adjusted for patient and hospital variables identified the XDB door-to-needle time at which no mortality advantage for X-PCI over O-FT was present. Eighty-one percent of X-PCI patients were matched (n=9506) to O-FT patients (n=9506). In the matched cohort, X-PCI was performed with delays >90 minutes in 68%. Multivariable analysis found no mortality advantage for X-PCI over O-FT when XDB door-to-needle time exceeded ~120 minutes. CONCLUSION: PCI-related delays are extensive among patients transferred for X-PCI and are associated with poorer outcomes. No differential excess in mortality was seen with X-PCI compared with O-FT even with long PCI related delays, but as XDB door-to-needle time times increase, the mortality advantage for X-PCI over O-FT declines. PMID- 22064593 TI - Frailty is independently associated with short-term outcomes for elderly patients with non-ST-segment elevation myocardial infarction. AB - BACKGROUND: For the large and growing population of elderly patients with cardiovascular disease, it is important to identify clinically relevant measures of biological age and their contribution to risk. Frailty is an emerging concept in medicine denoting increased vulnerability and decreased physiological reserves. We analyzed the manner in which the variable frailty predicts short term outcomes for elderly non-ST-segment elevation myocardial infarction patients. METHODS AND RESULTS: Patients aged >= 75 years, with diagnosed non-ST segment elevation myocardial infarction were included at 3 centers, and clinical data including judgment of frailty were collected prospectively. Frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale. The impact of the comorbid conditions on risk was quantified by the coronary artery disease-specific index. Of 307 patients, 149 (48.5%) were considered frail. By multiple logistic regression, frailty was found to be strongly and independently associated with risk for the primary composite outcome (death from any cause, myocardial reinfarction, revascularization due to ischemia, hospitalization for any cause, major bleeding, stroke/transient ischemic attack, and need for dialysis up to 1 month after inclusion) (odds ratio, 2.2; 95% confidence interval, 1.3-3.7), in-hospital mortality (odds ratio, 4.6; 95% confidence interval, 1.3-16.8), and 1-month mortality (odds ratio, 4.7; 95% confidence interval, 1.7-13.0). CONCLUSIONS: Frailty is strongly and independently associated with in-hospital mortality, 1-month mortality, prolonged hospital care, and the primary composite outcome. The combined use of frailty and comorbidity may constitute an ultimate risk prediction concept in regard to cardiovascular patients with complex needs. PMID- 22064594 TI - Mild retinopathy is a risk factor for cardiovascular mortality in Japanese with and without hypertension: the Ibaraki Prefectural Health Study. AB - BACKGROUND: It is unclear whether mild hypertensive retinopathy is a risk factor for mortality. This study examined whether mild hypertensive retinopathy could be a risk factor for cardiovascular mortality in subjects with and without hypertension. METHODS AND RESULTS: In this cohort study, 87 890 individuals (29 917 men and 57 973 women) 40 to 79 years of age in 1993 were followed up until 2008. Retinal photography was classified as normal, grade 1, or grade 2 based on the Keith-Wagener-Barker system. Risk ratios for all-cause and cause-specific mortality for each classification were calculated with Cox proportional hazards regression models. Covariates included age, systolic blood pressure, antihypertensive medication use, and other cardiovascular risk factors. Multivariable hazard ratios for total cardiovascular disease mortality were 1.24 (95% confidence interval [CI], 1.12-1.38) and 1.23 (95% CI, 1.03-1.47) for grades 1 and 2 among men and 1.12 (95% CI, 1.01-1.24) and 1.44 (95% CI, 1.24-1.68) for grades 1 and 2 among women, respectively. Hazard ratios for total stroke mortality were 1.31 (95% CI, 1.13-1.53) and 1.38 (95% CI, 1.08-1.77) for grades 1 and 2 among men and 1.30 (95% CI, 1.12-1.50) and 1.70 (95% CI, 1.36-2.11) for grades 1 and 2 among women, respectively. For both hypertensive and normotensive subjects of each sex, multivariable hazard ratios for all-cause mortality, total cardiovascular mortality, and total stroke mortality were significantly higher for grade 1 or 2 compared with normal. CONCLUSIONS: Mild hypertensive retinopathy is a risk factor for cardiovascular mortality independently of cardiovascular risk factors among men and women with and without hypertension. PMID- 22064595 TI - Statin use in outpatients with obstructive coronary artery disease. AB - BACKGROUND: Clinical trials have shown that statin therapy reduces cardiovascular morbidity and mortality in patients with coronary artery disease (CAD), even among patients with low-density lipoprotein cholesterol levels <100 mg/dL. We sought to determine the extent to which patients with obstructive CAD in routine outpatient care are treated with statins, nonstatins, or no lipid-lowering therapy. METHODS AND RESULTS: Within the American College of Cardiology's Practice Innovation and Clinical Excellence (PINNACLE) outpatient registry, we examined rates of treatment with statin and nonstatin medications in 38 775 outpatients with obstructive CAD (history of myocardial infarction or coronary revascularization) and without documented contraindications to statin therapy. Among these patients, 30 160 (77.8%) were prescribed statins, 2042 (5.3%) were treated only with nonstatin lipid-lowering medications, and 6573 (17.0%) were untreated. Lack of medical insurance was associated with no statin treatment, and male sex, coexisting hypertension, and a recent coronary revascularization were associated with statin treatment. Among those not on any lipid-lowering therapy, low-density lipoprotein cholesterol levels were available for 51.2% (3365/6573). Among these untreated patients, low-density lipoprotein cholesterol levels were <100 mg/dL in 1794 patients (53.3%) and >= 100 mg/dL in 1571 patients (46.7%). CONCLUSIONS: Despite robust clinical trial evidence, a substantial number of patients with obstructive CAD remain untreated with statins. A small proportion were treated with nonstatin therapy, and 1 in 6 patients was simply untreated; half of the untreated patients had low-density lipoprotein cholesterol values <100 mg/dL. These findings illustrate important opportunities to improve lipid management in outpatients with obstructive CAD. PMID- 22064596 TI - Identification of a danger-associated peptide from apolipoprotein B100 (ApoBDS-1) that triggers innate proatherogenic responses. AB - BACKGROUND: Subendothelial deposited low-density lipoprotein particles are a known inflammatory factor in atherosclerosis. However, the causal components derived from low-density lipoprotein are still poorly defined. Apolipoprotein B100 (ApoB100) is the unexchangeable protein component of low-density lipoprotein, and the progression of atherosclerosis is associated with immune responses to ApoB100-derived peptides. In this study, we analyzed the proinflammatory activity of ApoB100 peptides in atherosclerosis. METHODS AND RESULTS: By screening a peptide library of ApoB100, we identified a distinct native peptide referred to as ApoB100 danger-associated signal 1 (ApoBDS-1), which shows sequence-specific bioactivity in stimulation of interleukin-8, CCL2, and interleukin-6. ApoBDS-1 activates mitogen-activated protein kinase and calcium signaling, thereby effecting the expression of interleukin-8 in innate immune cells. Ex vivo stimulation of carotid plaques with ApoBDS-1 enhances interleukin-8 and prostaglandin E2 release. Furthermore, we demonstrated that ApoBDS-1-positive peptide fragments are present in atherosclerotic lesions using immunoassays and that low-molecular-weight fractions isolated from plaque show ApoBDS-1 activity inducing interleukin-8 production. CONCLUSIONS: Our data show that ApoBDS-1 is a previously unrecognized peptide with robust proinflammatory activity, contributing to the disease-promoting effects of low-density lipoprotein in the pathogenesis of atherosclerosis. PMID- 22064597 TI - m-Calpain induction in vascular endothelial cells on human and mouse atheromas and its roles in VE-cadherin disorganization and atherosclerosis. AB - BACKGROUND: Although dysfunction of VE-cadherin-mediated adherence junctions in vascular endothelial cells (ECs) is thought to be one of the initial steps of atherosclerosis, little is known regarding how VE-cadherin is disrupted during atherogenic development. This study focused on the role of calpain, an intracellular cysteine protease, in the proteolytic disorganization of VE cadherin and subsequent progression of atherosclerosis. METHODS AND RESULTS: Increased expression of m-calpain was observed in aortic ECs in atherosclerotic lesions in humans and low-density lipoprotein receptor-deficient (ldlr(-/-)) mice. Furthermore, proteolytic disorganization of VE-cadherin was shown in aortic ECs in ldlr(-/-) and apolipoprotein E-deficient (apoE(-/-)) mice. Long-term administration of calpain inhibitors into these mice attenuated atherosclerotic lesion development and proinflammatory responses, as well as VE-cadherin disorganization, without normalization of plasma lipid profiles. Furthermore, in vivo transfection of m-calpain siRNA to ldlr(-/-) mice prevented disorganization of VE-cadherin and proatherogenic hyperpermeability in aortic ECs. Treatment of cultured ECs with oxidized LDL, lysophosphatidylcholine, or LDL pretreated with secreted phospholipase A(2) led to the induction of m-calpain but not of MU calpain, thereby eliciting selective m-calpain overactivation. These data suggest that lysophosphatidylcholine-induced m-calpain directly cleaves a juxtamembrane region of VE-cadherin, resulting in dissociation of beta-catenin from the VE cadherin complex, disorganization of adherence junctions, and hyperpermeability in ECs. CONCLUSIONS: Subtype-selective induction of m-calpain in aortic ECs during atherosclerotic progression is associated with proteolytic disorganization of VE-cadherin and proatherogenic hyperpermeability in cells. Thus, a strategy to selectively inhibit m-calpain may be useful for the therapeutic treatment of patients with atherosclerosis. PMID- 22064598 TI - 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. PMID- 22064599 TI - 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. PMID- 22064600 TI - 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. PMID- 22064601 TI - 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. PMID- 22064602 TI - The 5alpha-androstanedione pathway to dihydrotestosterone in castration-resistant prostate cancer. AB - The survival and progression of prostate cancer are generally dependent on expression of the androgen receptor (AR), as well as the availability of endogenous AR agonists. Originating from the gonads, testosterone is released into circulation and is converted by steroid-5alpha-reductase in prostate cancer to 5alpha-dihydrotestosterone (DHT), potently activating AR and driving tumor progression. Advanced prostate cancer is initially treated with gonadal testosterone depletion, which suppresses this cascade of events and typically leads to a treatment response. Eventually, resistance to testosterone deprivation occurs with "castration-resistant" prostate cancer (CRPC) and is driven by the intratumoral synthesis of DHT. The generation of DHT occurs in large part from adrenal 19-carbon precursor steroids, which are dependent on expression of CYP17A1. Although the path from adrenal precursor steroids to DHT was generally thought to require 5alpha-reduction of testosterone, recent data suggest that it instead involves conversion from Delta-androstenedione by steroid-5alpha reductase isoenzyme-1 to 5alpha-androstanedione, followed by subsequent conversion to DHT. The 5alpha-androstanedione pathway to DHT therefore bypasses testosterone entirely. Abiraterone acetate effectively inhibits CYP17A1, blocks the synthesis of androgens, and extends the survival of men with CRPC. Further progress in the hormonal treatment of CRPC is dependent on an understanding of the mechanisms that underlie CRPC and resistance to abiraterone acetate. PMID- 22064603 TI - Angiotensin-converting enzyme DD polymorphism is associated with poor coronary collateral circulation in patients with coronary artery disease. AB - OBJECTIVES: Although association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and cardiovascular diseases was reported by many studies, the relation between ACE I/D polymorphism and coronary collateral circulation (CCC) has not been studied yet. The aim of the present study was to investigate a possible relationship between ACE I/D polymorphism and CCC. METHODS: Patients who were subjected to coronary angiography in the 2006 to 2009 period and had at least a completely occluded major artery were included in this study. To classify collateral circulation, we used the Rentrop classification. Patients were classified as having poor CCC (Rentrop grades 0 to 1) or good CCC (Rentrop grades 2 to 3). Gene polymorphism was detected through the detailed melting curve analysis of polymerase chain reaction products after amplification using real-time polymerase chain reaction method and LightCycler 1.5 apparatus. RESULTS: We prospectively studied 113 patients who had at least 1 totally occluded major epicardial coronary artery. Forty-seven patients had poor CCC and 67 patients had good CCC. There were no differences among groups in age, sex, risk factors, lipid profile, uses of cardiovascular drugs, and number of diseased vessels. Plasma ACE levels were significantly higher in poor CCC group (P < 0.001). The frequency of DD polymorphism was higher in the poor CCC group (P < 0.001). In allele frequency, we found that the frequency of the D allele was higher in poor CCC group than in the good CCC group (95% confidence interval [CI], 2.16-7.38; P < 0.001). Multiple regression analysis with CCC development as the dependent variable revealed that the presence of total occlusion of the left circumflex artery (95% CI, 1.29-6.6; P = 0.001), ACE DD genotype (95% CI, 2.55 12.79; P = 0.001), presence of diabetes (95% CI, 1.03-3.16; P = 0.005), and pulse pressure (95% CI, 1.04-1.56; P = 0.045) were independent determinants of poor coronary collateral development. CONCLUSIONS: This study showed that ACE DD polymorphism is associated with poor CCC. Poor collateral circulation in patients carrying the D allele may be associated with endothelial dysfunction and elevated blood ACE levels in these patients. PMID- 22064604 TI - CD200 expression in B-cell chronic lymphoproliferative disorders. AB - BACKGROUND: Flow cytometry immunophenotyping (FCIP) is used for rapid, specific diagnosis of B-chronic lymphoproliferative disorders (BCLPDs). However, cases may deviate from the typical immunophenotype; therefore, there is a need for adding new marker(s) for differentiating BCLPDs.Lately, few researches highlighted CD200 expression in some BCLPDs. Our aim was to evaluate CD200 expression in different BCLPDs and whether adding CD200 to BCLPD-FCIP routine panels could improve the ability of their differential diagnosis. METHODS: We evaluated CD200 expression in 49 BCLPD patients and 26 age- and sex-matched control subjects. Flow cytometry immunophenotyping first panel included CD5, CD19, sIg, CD23, CD22, CD79b, and FMC7; for BCLPDs other than chronic lymphocytic leukemia (CLL) and mantle cell lymphoma, CD11c, CD103, CD25, and CD10 were evaluated. RESULTS: Using tricolor FCIP, CD200 showed high bright expression on CD5/19-positive clone in all B-CLL patients (100%), with a mean of 94% (SD, 11%); in the 2 cases of hairy cell leukemia, CD200 was brightly expressed on 96% and 99% of cells. In all other BCLPDs including mantle cell lymphoma, follicular lymphoma and splenic marginal zone lymphoma, CD200 expression (on CD19/22-positive cells) was less than 20% with a mean of 10% (SD, 8%) and a dim pattern. CD200 expression was significantly higher in CLL compared with non-Hodgkin lymphoma groups (P < 0.001). CONCLUSIONS: Evaluating CD200 expression has a great impact on accurate BCLPDs diagnosis and could be added to the BCLPD routine panels. The high expression of CD200 in B cell CLL and hairy cell leukemia could open the option for targeted immune (anti CD200) therapy. PMID- 22064605 TI - Comorbidities in gouty arthritis. AB - BACKGROUND: Gouty arthritis is increasing in prevalence in men and women, particularly in older age groups. METHODS: A PubMed search was conducted to identify common comorbidities associated with gouty arthritis, their impact on quality of life, and strategies to manage gouty arthritis and its associated comorbidities. RESULTS: Gouty arthritis is associated with numerous comorbidities that are increasing in prevalence (chronic kidney disease [CKD], hypertension, obesity, diabetes, metabolic syndrome, and cardiovascular disease) and that negatively impact long-term prognosis and quality of life. Therefore, certain considerations and precautions are necessary when treating gouty arthritis in these patients. For example, nonsteroidal anti-inflammatory drugs can cause acute renal toxicity or worsen CKD and should be avoided in this population. Dosage adjustments are recommended when using colchicine and urate-lowering therapy in patients with CKD, which may limit efficacy. Febuxostat may be used in patients with mild to moderate renal impairment, but insufficient information is available for use in patients with creatinine clearance of less than 30 mL/min. Numerous drug-drug interactions in patients with gouty arthritis and comorbidities may alter serum uric acid levels. Several interleukin 1beta inhibitors, which target the underlying inflammatory mechanism of gouty arthritis and many of its comorbidities, are in development and may provide an option for patients not adequately managed with other treatments. CONCLUSIONS: Gouty arthritis is associated with renal, metabolic, and cardiovascular comorbidities that negatively impact overall health. The management of gouty arthritis in the presence of comorbidities is particularly challenging because of contraindications, the need for dosage adjustments, and polypharmacy. PMID- 22064606 TI - The safety and efficacy of etanercept on cardiac functions and lipid profile in patients with active rheumatoid arthritis. AB - OBJECTIVES: Patients with rheumatoid arthritis (RA) are known to be at increased cardiovascular risk. Etanercept is a tumor necrosis factor alpha (TNF-alpha) blocking agent that has been successfully used in the treatment of RA. We sought to assess the effects of etanercept on cardiac functions and lipid profile in RA patients without overt cardiac disease. METHODS: Sixteen patients with active RA were recruited to the study prospectively. Etanercept was administered subcutaneously twice a week for 6 months. Clinical and laboratory predictors of RA activity and lipid profile were evaluated at baseline and at 6 months. The systolic and diastolic function parameters of the left ventricle were obtained by echocardiographic examination and included mitral inflow Doppler and tissue Doppler imaging. RESULTS: Sixteen patients (13 women; median age, 48 years [range, 27-69 years]) completed the study. Patients' 28-item Disease Activity Score and Health Assessment Questionnaire scores were significantly reduced by treatment (6.35 to 4.45 [P < 0.001] and 2.0 to 0.75 [P = 0.005], respectively). Diastolic dysfunction was detected in 6 patients (37.5%) (3 in grade 1 and 3 in grade 2) by mitral inflow Doppler and the tissue Doppler parameters before the treatment. No significant change in diastolic dysfunction was observed during follow-up (6/16 to 5/16, P = 0.164). In addition, there were also no significant differences in the left ventricular ejection fraction (65.8-66.9, P = 0.168) and lipid profiles after 6 months of etanercept treatment. CONCLUSIONS: Etanercept treatment was safe for use as regards cardiac functions and lipid profiles and effective on RA parameters during 6-month follow-up in patients with active RA. PMID- 22064607 TI - Minimum 10-year follow-up of arthroscopic intra-articular Bankart repair using bioabsorbable tacks. AB - BACKGROUND: There are few long-term studies evaluating functional outcomes and rates of arthrosis after arthroscopic Bankart repair with bioabsorbable tacks. PURPOSE: We evaluated the clinical and radiographic results of arthroscopic Bankart repair using intra-articular bioabsorbable tacks at a minimum of 10 years' follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-two consecutive patients were retrospectively identified. Twenty patients (63%) were evaluated at a mean follow-up of 13.5 years (range, 10.75-17.5 years) and average age of 43 years (range, 28-73 years). The surgical shoulder (SS) was compared with a healthy control shoulder (CS) in 15 of 20 patients. Outcome tools included the Western Ontario Shoulder Instability Index (WOSI) and Disabilities of the Shoulder, Arm, and Hand (DASH). Blinded, independent evaluators performed physical examinations and reviewed radiographs. RESULTS: Thirteen patients (65%) had stable shoulders, 5 of 7 (25%) failed by dislocation, and 2 of 7 (10%) failed by signs of anterior instability on examination. Three patients underwent revision stabilization surgery. Average time to failure was 4.2 years (range, 0.25-14.7 years). Average WOSI and DASH scores were 80% and 7.3, respectively. The CS faired better than SS in WOSI scores (97% vs 83%, respectively; P = .008), main DASH scores (0.39 vs 6.79, respectively; P = .024), and the DASH sports module (0.00 vs 10.94, respectively; P = .043). Patients lost 5.9 degrees of passive forward flexion (P = .031) and 4.3 degrees of passive external rotation (P = .001). Forty percent returned to their preoperative sports level. Higher grades of arthrosis were seen in the SS (20% absent, 40% mild, 25% moderate, and 15% severe) versus CS (P = .002). CONCLUSION: At long-term follow-up, 65% of patients treated with an arthroscopic Bankart repair using bioabsorbable tacks had a well-functioning, stable shoulder. Disability scores were greatest with sports; however, the majority of patients had well-preserved ranges of motion and good functional WOSI scores. Despite this, 40% had evidence of moderate to severe glenohumeral arthrosis. PMID- 22064608 TI - Retention of movement pattern changes after a lower extremity injury prevention program is affected by program duration. AB - BACKGROUND: Changes in movement patterns have been repeatedly observed immediately after completing a lower extremity injury prevention program. However, it is not known if movement pattern changes are maintained after discontinuing the training program. HYPOTHESIS: The ability to maintain movement pattern changes after training has ceased may be influenced by the program's duration. The authors hypothesized that among individuals who completed either a 3-month or 9-month training program and who demonstrated immediate movement pattern changes, only those who completed the 9-month training program would maintain movement pattern changes after a 3-month period of no longer performing the exercises. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 140 youth soccer athletes from 15 separate teams volunteered to participate. Athletes' movement patterns were assessed using the Landing Error Scoring System (LESS) at pretest, posttest, and 3 months after ceasing the program (retention test). Eighty-four of the original 140 participants demonstrated improvements in their LESS scores between pretest and posttest (change in LESS score >0) and were included in the final analyses for this study (n = 84; 20 boys and 64 girls; mean age, 14 +/- 2 years; age range, 11-17 years). Teams performed 3-month (short duration group) and 9-month (extended-duration group) injury prevention programs. The exercises performed were identical for both groups. Teams performed the programs as part of their normal warm-up routine. RESULTS: Although both groups improved their total LESS scores from pretest to posttest, only the extended duration training group retained their improvements 3 months after ceasing the injury prevention program (F(2,137) = 3.38; P = .04). CONCLUSION: Results suggest that training duration may be an important factor to consider when designing injury prevention programs that facilitate long-term changes in movement control. PMID- 22064609 TI - Going to the USA--a US headache center from an Italian perspective. AB - During a period I spent at the UCSF Headache Center in the USA, I noted striking differences between the US health-care system and the Italian one in which I was trained. Here, I aim to outline some of these differences from a scientific-and, more importantly, from a sociocultural-point of view. Awareness of these aspects may help us to better understand different approaches to the diagnosis and treatment of various diseases, including headache. PMID- 22064610 TI - Advances in understanding and treatment of Tourette syndrome. AB - Tourette syndrome is a hereditary, childhood-onset neurodevelopmental disorder that was first clearly described in France in 1885. This disorder is characterized by sudden, rapid, recurrent, nonrhythmic movements (motor tics) or sounds (vocal or phonic tics), often preceded by premonitory sensations or urges. Some individuals also have psychiatric comorbidities, notably attention-deficit hyperactivity disorder or obsessive-compulsive disorder. Tourette syndrome occurs worldwide, in all races and ethnicities, in both sexes and in children as well as in adults. Estimates of its prevalence in children vary, with rates of up to 1% being reported, but rates of 0.3-0.8% are thought to accurately reflect the occurrence of the disorder. Research has led to progress in many aspects of Tourette syndrome, although many questions and unmet needs remain. For example, except for rare cases, the genetic basis remains elusive. The anatomical and neuronal changes in the brain that underlie Tourette syndrome are also unclear, although the evidence increasingly implicates alterations in basal ganglia function. Treatment is often unnecessary for individuals with mild tics, but for those with moderate to severe forms of the syndrome, some drugs are available, albeit frequently ineffective. Behavioral and surgical therapies, in particular deep brain stimulation, are currently undergoing development and show promising results. This Review examines the history of Tourette syndrome and describes its clinical presentation. The article also provides an overview of the epidemiology and pathophysiology of this disorder. Current treatment strategies and potential future therapies are also discussed. PMID- 22064611 TI - Depression-a study of 80 cases. AB - The present study refers to an analysis of eighty cases of depression. The annual incidence in our psychiatric population ranges from 17-20% of all the new psychiatric cases. The peak incidence was observed in the age group of 26-45 years, without any particular affinity to either sex. 83.8% of our sample were married and those hailing from nuclear families formed the larger proportion (58.75%).Somatic symptoms were the predominant presenting complaint in 61.3% of our patients. Another noteworthy observation was significant number of depressives harboured guilt feelings (76.3%) and suicidal ideas (73.8%). Other findings are also discussed. PMID- 22064612 TI - N'-[(1E)-4-Diethyl-amino-2-hy-droxy-benz-idene]benzohydrazide. AB - In the title compound, C(18)H(21)N(3)O(2), the dihedral angle between the phenyl and benzene rings is 36.85 (10) degrees . The methyl C atom of one of the ethyl groups is disordered over two positions with site occupancies of 0.810 (8) and 0.190 (8). The mol-ecular structure is stabilized by a classical intra-molecular O-H?N hydrogen bond. The crystal structure exhibits weak inter-molecular N-H?O, C H?O and C-H?pi inter-actions. PMID- 22064613 TI - Psychometric properties of the Starkstein Apathy Scale in patients with early untreated Parkinson disease. AB - BACKGROUND: : Although the 14-item Starkstein Apathy Scale (SAS) is recommended to screen for and measure the severity of apathetic symptoms in Parkinson disease (PD), the psychometric attributes of this scale have not yet been fully evaluated. OBJECTIVE: : The authors examined the reliability, factor structure, and discriminant validity of the SAS in 194 nondemented patients with early untreated PD. DESIGN: : Cross-sectional multicenter population-based study from Western and Southern Norway. MEASUREMENTS: : Standardized rating scales for parkinsonism and neuropsychiatric symptoms. RESULTS: : The SAS showed fair internal consistency (Cronbach's alpha = 0.69) and exploratory factor analysis identified two factors: the first factor (24.2% of the variance) represented cognitive-behavioral aspects of apathy (items 1, 2, and 4-8; Cronbach's alpha = 0.74) and the second factor (15.0% of the variance) a general apathy dimension (items 3 and 9-14; Cronbach's alpha = 0.52). The correlation between these two factors was low (Spearman's r = 0.19, N = 194, p = 0.008), indicating clinically distinct dimensions, but both factor scores were strongly related to the total SAS score (Spearman's r > 0.6, N = 194, p < 0.0005). Item 3 (insight or self reflection) showed a negative item-total correlation, and removing this item raised the Cronbach's alpha of the second factor to 0.70, but did not substantially alter the other results. Both the total score and factor scores of SAS showed fair discriminant validity. CONCLUSIONS: : Although the SAS showed fairly good psychometric properties and the exploratory factor analysis suggested a two-factor solution, the results with this PD sample indicate that item 3 is ambiguous and should be considered removed from the scale. PMID- 22064614 TI - Poly[[aqua-tris-(MU(4)-benzene-1,2-dicarboxyl-ato)dilanthanum(III)] hemihydrate]. AB - The asymmetric unit of the title coordination polymer, {[La(2)(C(8)H(4)O(4))(3)(H(2)O)].0.5H(2)O}(n), contains two independent La(III) atoms, one of which is surrounded by eight carboxyl-ate-O atoms from six benzene 1,2-dicarboxyl-ate (BDC) anions in a bicapped trigonal-prismatic geometry. The other La(III) atom is nine-coordinated in a tricapped trigonal-prismatic geometry, formed by eight carboxyl-ate-O atoms from six BDC anions and a coordinated water mol-ecule. The BDC anions bridge the La(III) atoms, forming a two-dimensional polymeric complex parallel to (001). The crystal structure contains weak O-H?O and non-classical C-H?O hydrogen bonds. A C-H?pi inter-action is also present in the crystal structure. The uncoordinated water molecule shows half-occupation. PMID- 22064617 TI - Education and psychological test scores. AB - Education, a long neglected variable affecting psychological test score, is in search of reemphasis. Some evidence for this has accumulated on the psychological tests constructed and standardized here at the department of Psychiatry, P.G.I., Chandigarh. Tentative norms prepared education wise on WAIS-Verbal section, PGI Memory Scale, Proverb and Similarity Tests, Psychoticism Questionnaire, and PGI MQN 2, for adults, in the age range of 16-50, are reported. The results showed marked difference in the mean scores of different educational categories and thus stressed the need for reporting norms separately for different educational levels. PMID- 22064618 TI - (R(P),R(P))-Bis[(3-menthyloxy)(phenyl)-phosphino-yl] disulfide. AB - The molecule of the title compound, C(32)H(48)O(4)P(2)S(2), has 2 symmetry, the mid-point of the S-S bond being located on a twofold rotation axis. The two tetra hedral P units are linked by a S-S bond with a P-S-S-P torsion angle is 131.19 (6) degrees . The dihedral angle between two phenyl rings is 12.66 (13) degrees . The cyclo-hexane ring of the menthoxyl group displays a chair conformation. Weak inter-molecular C-H?O hydrogen bonding is present in the crystal structure. PMID- 22064619 TI - fac-(2-Amido-ethyl-kappaC,O)trichlorido(urea-kappaO)tin(IV). AB - The Sn atom in the title compound, [Sn(C(3)H(6)NO)Cl(3)(CH(4)N(2)O)], is octa hedrally coordinated within a CCl(3)NO donor set provided by a chelating amido ethyl ligand (C and O), a urea-O atom and three facially arranged Cl atoms. Systematic variations in the Sn-Cl bond distances are correlated with the relative trans influence exerted by the C and carbonyl-O atoms. The three dimensional crystal packing is stabilized by N-H?O and N-H?Cl hydrogen bonds. PMID- 22064620 TI - 4-[(E)-(4-Diethyl-amino-2-hy-droxy-benzyl-idene)amino]-1,5-dimethyl-2-phenyl-1H pyrazol-3(2H)-one. AB - In the title compound, C(22)H(26)N(4)O(2), the phenyl ring and hy-droxy-benzene group are twisted with respect to the central pyrazolone ring, making dihedral angles of 54.05 (5) and 21.80 (6) degrees , respectively. One of the ethyl groups is disordered over two positions with site occupancies of 0.872 (6) and 0.128 (6). The mol-ecular structure features short intra-molecular O-H?N and C-H?O contacts. The crystal packing exhibits weak inter-molecular C-H?O and C-H?pi inter-actions. PMID- 22064621 TI - (2,7-Dimeth-oxy-naphthalen-1-yl)(2,4,6-trimethyl-phen-yl)methanone. AB - In the title compound, C(22)H(22)O(3), the dihedral angle between the naphthalene ring system and the benzene ring is 82.93 (5) degrees . The bridging carbonyl C C(=O)-C plane makes dihedral angles of 50.11 (6) and 46.87 (7) degrees , respectively, with the naphthalene ring system and the benzene ring. In the crystal, three types of weak inter-molecular C-H?O inter-actions are observed. PMID- 22064622 TI - Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis. AB - BACKGROUND: The majority of pancreatic cancers are diagnosed at an advanced stage. As surgical resection remains the only hope for cure, more aggressive surgical approaches have been advocated to increase resection rates. Institutions have begun to release data on their experience with pancreatectomy and simultaneous arterial resection (AR), which has traditionally been considered a general contraindication to resection. The aim of the present meta-analysis was to evaluate the perioperative and long-term outcomes of patients with AR during pancreatectomy for pancreatic cancer. METHODS: The Medline, Embase, and Cochrane Library and J-East databases were systematically searched to identify studies reporting outcome of patients who underwent pancreatectomy with AR for pancreatic cancer. Studies that reported perioperative and/or long-term results after pancreatectomy with AR were eligible for inclusion. Meta-analyses included comparative studies providing data on patients with and without AR and were performed using a random effects model. RESULTS: The literature search identified 26 studies including 366 and 2243 patients who underwent pancreatectomy with and without AR. All studies were retrospective cohort studies and the methodological quality was moderate to low. Meta-analyses revealed AR to be associated with a significantly increased risk for perioperative mortality [Odds ratio (OR) = 5.04; 95% confidence interval (CI), 2.69-9.45; P < 0.0001; I2 = 24%], poor survival at 1 year (OR = 0.49; 95% CI, 0.31-0.78; P = 0.002; I2 = 35%) and 3 years (OR = 0.39; 95% CI, 0.17-0.86; P = 0.02; I2 = 49%) compared with patients without AR. The increased perioperative mortality (OR = 8.87; 95% CI, 3.40-23.13; P < 0.0001; I2 = 5%) and lower survival rate at 1 year (OR = 0.50; 95% CI, 0.31-0.82; P = 0.006; I2 = 40%) was confirmed in the comparison to patients undergoing venous resection. Despite substantial perioperative mortality, pancreatectomy with AR was associated with more favorable survival compared with patients who did not undergo resection for locally advanced disease. CONCLUSIONS: AR in patients undergoing pancreatectomy for pancreatic cancer is associated with a poor short and long-term outcome. Pancreatectomy with AR may, however, be justified in highly selected patients owing to the potential survival benefit compared with patients without resection. These patients should be treated within the bounds of clinical trials to assess outcomes after AR in the era of modern pancreatic surgery and multimodal therapy. PMID- 22064623 TI - Use of direct observed therapy to confirm compliance in a warfarin clinic. AB - Anticoagulation therapy poses multiple risks to patients and contributes to thousands of health-care dollars in treating complications. These risks have been shown to decrease when patients are monitored in a warfarin clinic. Even in the setting of a warfarin clinic, complications can occur, most of which are related to patient compliance. Warfarin clinics have limited options for addressing issues of compliance. Direct observed therapy is a technique that warfarin clinics can use to highlight issue of noncompliance to more safely manage patients on warfarin. A short course of direct observed therapy is a feasible method to confirm compliance with anticoagulation medication. Direct observed therapy allows providers to adjust medication based on real data and not just patient statements of compliance. Direct observed therapy also allows providers to confront patients with tangible evidence of noncompliance that cannot be refuted. PMID- 22064624 TI - What stands in the way of technology-mediated patient safety improvements?: a study of facilitators and barriers to physicians' use of electronic health records. AB - OBJECTIVES: For electronic health record (EHR) systems to have a positive impact on patient safety, clinicians must be able to use these systems effectively after they are made available. This study's objective is to identify and describe facilitators and barriers to physicians' use of EHR systems. METHODS: Twenty research interviews were conducted with attending physicians who were using EHR at 1 of 2 Midwest community hospitals and/or at their respective outpatient clinics. RESULTS: Analyses yielded more than 200 perceived facilitators and barriers, comprising 19 distinct categories. Categories of facilitators/barriers related to user attribute included learning, typing proficiency, understanding the EHR system, motivation/initiative, and strategies/workarounds. Categories related to system attributes were supporting hardware/software and system speed, functionality, and usability. Categories related to support from others were formal technical support, formal training, and informal support from colleagues. Categories of organizational facilitators/barriers were time allowance and interinstitutional integration. Categories of environmental facilitators/barriers were physical space, electricity, wireless connectivity, and the social environment. CONCLUSIONS: Together, the broad set of discovered facilitators and barriers confirms and expands prior research on the facilitators and barriers to health information technology use. The depth of reported information on each facilitator and barrier made possible by qualitative interview methods contributes to the theoretical understanding of facilitators and barriers to EHR use. Equally as important, this study provides an information base from which relevant policy and design interventions can be launched to improve the use of EHR systems and, thus, patient safety. PMID- 22064625 TI - Error detection and recovery in dialysis nursing. AB - OBJECTIVES: Our aim for this study was to evaluate dialysis nurses' ability to detect and recover from nursing errors. METHODS: Two clinical cases with a total of 12 embedded errors were constructed. The errors were based on real events but were modified for the experimental design by an expert dialysis nurse. A total of 31 registered nurse subjects "talked aloud" as they read through the 2 cases and answered a set of predesigned knowledge-based and procedural questions. The talk aloud sessions were recorded and transcribed for analysis of errors detected and recovered. RESULTS: Performance on procedurally based error detection and recovery was significantly higher as a function of expertise (P < 0.05), where more-experienced nurses performed better than the less-experienced nurses in detecting and recovering procedurally based errors. However, no differences were found for knowledge-based errors. CONCLUSIONS: Expert nurses develop a special ability to detect and recover from nursing errors, but the nature of these errors depends on the nature of the task. Dialysis nursing requires more knowledge of procedures rather than conceptual knowledge in their routine work, and thus, the nurses develop better procedurally based skills. This raises concern about nurses making knowledge-based or conceptual errors, which, if made, are not detected or corrected. The need for understanding conceptual knowledge underlying procedures and for training in error detection and correction strategies is discussed in the context of nursing. PMID- 22064626 TI - The nature and causes of unintended events reported at 10 internal medicine departments. AB - OBJECTIVE: This study aimed to examine the nature and causes of unintended events (UEs) at internal medicine departments (IMD). METHODS: An observational study was conducted at 10 IMDs in 8 Dutch hospitals. The study period per participating department was 5 to 14 weeks. During this period, staff were asked to report all UEs concerning patient safety. To identify underlying root causes, experienced researchers analyzed the reports using a standardized root cause analysis method called PRISMA medical. RESULTS: Hospital staff reported 625 UEs. Medication related UEs were the most reported events (42%). Of all reported UEs, 12% involved the collaboration between the IMD and other departments within the hospital.On the basis of the 625 UEs, 920 root causes were identified. The mean (SD) number of root causes per incident was 1.47 (0.68). Human root causes were related to 83.2% of the UEs, organizational root causes were related to 15.7%, technical root causes were related to 7%, and other root causes were related to 8.6% of the UEs.More than half of the reported UEs reached the patient (62%), with suboptimal care as the most frequently occurring consequence (44.7%). Physical injury occurred in 10.3% of the UEs. CONCLUSIONS: Hospital staff reporting UEs seems to be a good method for gaining insight into the types of UEs that occur at hospital departments. Although many UEs had human causes, identifying technical and organizational causes is important for the development of successful improvement strategies considering their contribution to human error. Important targets for these strategies are the medication process and collaboration within the hospital. PMID- 22064629 TI - Tetra-kis(diethyl ether)tetra-MU(4)-oxido-octa-kis-(penta-fluoro-phen-yl)octa zinc. AB - Mol-ecules of the title compound, [Zn(8)(C(6)F(5))(8)O(4)(C(4)H(10)O)(4)], are located on a special position of site symmetry [Formula: see text]. As a result, there is just one quarter-mol-ecule in the asymmetric unit. The title compound features a Zn(4)O(4) cube. Each Zn atom in the cube carries a pentafluorophenyl substituent. Each O atom is bonded to a further Zn atom, which is connected to a pentafluorophenyl substituent and the O atom of a diethyl ether mol-ecule. All ether C atoms are disordered over two sets of sites with a site occupation factor of 0.51 (2) for the major occupied site. PMID- 22064628 TI - Genetics of susceptibility and treatment response in psoriatic arthritis. AB - Psoriatic arthritis (PsA), an inflammatory arthritis associated with psoriasis, has a wide spectrum of disease severity. The clinical heterogeneity in PsA probably reflects substantial genetic heterogeneity. In recent years, many genes that contribute to the pathogenesis of psoriasis and PsA have been identified, especially in Western cohorts. Emerging evidence from functional studies of candidate genes identified by genome-wide association studies is suggestive of an integrated, multi-tiered pathogenic model, comprising distinct signaling networks that affect skin barrier function, innate immune responses (involving NFkappaB and interferon signaling), and adaptive immune responses (involving CD8(+) T cells and type 17 T-helper-cell signaling). Although several genes--and variants thereof--within these pathways have been associated with susceptibility to psoriasis and PsA, replication in large multiethnic cohorts, fine mapping and resequencing efforts, together with functional studies of the variants, are warranted to better understand their role in disease susceptibility. With respect to pharmacogenetics, several candidate gene polymorphisms have been shown to influence responses to both traditional and biologic therapies in psoriasis and PsA, but confirmation in large prospective cohorts is required before the information can be used in the clinical setting. PMID- 22064630 TI - Does VSL#3 really improve symptoms in children with IBS? PMID- 22064631 TI - Endocrine and bone metabolic complications in chronic liver disease and after liver transplantation in children. AB - With improved survival of orthotopic liver transplantation (OLT) in children, prevention and treatment of pre- and posttransplant complications have become a major focus of care. End-stage liver failure can cause endocrine complications such as growth failure and hepatic osteodystrophy, and, like other chronic illnesses, also pubertal delay, relative adrenal insufficiency, and the sick euthyroid syndrome. Drug-induced diabetes mellitus post-OLT affects approximately 10% of children. Growth failure is found in 60% of children assessed for OLT. Despite optimisation of nutrition, rarely can further stunting of growth before OLT be prevented. Catch-up growth is usually observed after steroid weaning from 18 months post-OLT. Whether growth hormone treatment would benefit the 20% of children who fail to catch up in height requires testing in randomised controlled trials. Hepatic osteodystrophy in children comprises vitamin D deficiency rickets, low bone mass, and fractures caused by malnutrition and malabsorption. Vitamin D deficiency requires aggressive treatment with ergocalciferol (D2) or cholecalciferol (D3). The active vitamin D metabolites alphacalcidol or calcitriol increase gut calcium absorption but do not replace vitamin D stores. Prevalence of fractures is increased both before OLT (10%-28% of children) and after OLT (12%-38%). Most fractures are vertebral, are associated with low spine bone mineral density, and frequently occur asymptomatically, but they may also cause chronic pain. Fracture prediction in these children is limited. OLT in children is also associated with a greater risk of developing avascular bone necrosis (4%) and scoliosis (13%-38%). This article reviews the literature on endocrine and skeletal complications of liver disease and presents preventive screening recommendations and therapeutic strategies. PMID- 22064632 TI - Liver, hormones, and bones. PMID- 22064633 TI - Serum cystatin C correlates negatively with viral load in treatment-naive children with chronic hepatitis C. AB - OBJECTIVES: Hepatitis C virus (HCV) infection is a serious health problem that causes chronic infection in up to 85% of cases. HCV nonstructural (NS) cysteine protease, NS2/3, is required for viral replication in vivo. Cystatin C is a naturally occurring cysteine protease inhibitor in human cells. We aimed to investigate the relation between serum levels of cystatin C and HCV viremia in treatment-naive children with chronic hepatitis C. METHODS: Serum cystatin C levels were measured in 27 children with chronic hepatitis C and determined their relation with liver functions, histopathological parameters, and hepatitis C viral load. Serum cystatin C was compared with that of 25 age- and sex-matched healthy controls. RESULTS: Cystatin C was significantly higher in patients than in controls (1.4 +/- 0.47 vs 0.99 +/- 0.49; P = 0.006), and in those with low viremia than in those with moderate viremia (1.55 +/- 0.41 vs 0.99 +/- 0.43; P = 0.013). Cystatin C was not correlated with histopathological findings in liver biopsy (P > 0.05 for all). In addition, there was no significant difference of cystatin C levels in patients with normal versus those with elevated transaminases (P > 0.05). Of importance, cystatin C correlated negatively with viral load (P < 0.0001). CONCLUSIONS: Cystatin C levels correlated negatively with HCV viremia. This finding may reflect an inhibitory effect of cystatin C on HCV replication through inhibiting its NS2/3 and tempting for further studies for cystatin C as a possible adjuvant therapy for HCV infection. PMID- 22064634 TI - Review of measurement methods and clinical validation studies of noninvasive blood pressure monitors: accuracy requirements and protocol considerations for devices that require patient-specific calibration by a secondary method or device before use. AB - Existing standardized protocols for clinical validation of noninvasive blood pressure (BP) monitors do not have specific provisions for monitors that require patient-specific calibration by a secondary method or device before use. This article seeks to identify accuracy requirements and protocol considerations for such monitors. Measurement methods that require patient-specific calibration were reviewed to identify their clinical accuracy requirements. Validation studies of monitors that use these methods were reviewed to identify limitations in their protocols. For a monitor that requires patient-specific calibration, inadequate adaptation of existing protocols can fail to validate the accuracy of the monitor for its intended use. A protocol for such a monitor must have provisions to assess the monitor's accuracy in tracking intrapatient BP changes, from the calibrated level, after a calibration or between calibrations. Performing a patient-specific calibration with a patient at rest and immediately evaluating the monitor against a reference method with the patient also at rest will not assess this accuracy, because changes in BP at rest and over a short time are generally small compared with those that occur over 24 h. For validation purposes, intrapatient BP changes can be achieved by validating the monitor over an extended period or induced by means of physical maneuvers or pharmacological interventions. The secondary method or device used for the calibration must be accurate. The protocol must also have provisions to assess the monitor's ability to correct for changes in hydrostatic pressure, reject or correct for motion artefacts, and correct for other factors that affect measurement accuracy during use. There is a need to establish protocol provisions to ensure that noninvasive BP monitors that require patient-specific calibration are properly validated for their intended use before they are placed on the market or introduced into clinical use. PMID- 22064640 TI - Training and outcome monitoring in robotic urologic surgery. AB - The use of robot-assisted laparoscopic technology is rapidly expanding, with applicability in numerous disciplines of surgery. Training to perform robot assisted laparoscopic urological procedures requires a motivated learner, a motivated teacher or proctor, a curriculum with stepwise learning objectives, and regular access to a training robot. In light of the many constraints that limit surgical training, animal models should be utilized to quantifiably improve the surgical skills of residents and surgical fellows, before these skills are put into practice on patients. A system based on appropriate supervision, graduated responsibility, real-time feedback, and objective measure of progress has proven to be safe and effective. Surgical team education directed towards cohesion is perhaps the most important aspect of training. At present, there are very few published guidelines for the safe introduction of robotic urologic surgery at an institution. Increasing evidence demonstrates the effects of learning curve and surgical volume on oncological and functional outcomes in robotic surgery (RS). This necessitates the introduction of mechanisms and guidelines by which trainee surgeons can attain a sufficient level of skill, without compromising the safety of patients. Guidelines for outcome monitoring following RS should be developed, to ensure patient safety and sufficient baseline surgeon skill. PMID- 22064641 TI - Image-guided radiation therapy for muscle-invasive bladder cancer. AB - Organ preservation protocols that incorporate chemoradiotherapy have shown good efficacy in bladder cancer. Owing to changes in rectal filling, urinary inflow and subsequent bladder volume with bladder wall deformations, irradiation must take into account interfractional and intrafractional internal target motion. Growing evidence suggests that image guidance during irradiation is essential in order to appropriately treat bladder cancer in this way. We performed a literature search on the imaging techniques and margins used for radiation therapy planning in the context of whole-bladder and partial-bladder irradiation. The most common image-guided radiation therapy (IGRT) method was based on cone beam CT using anisotropic margins. The role of cine-MRI for the prediction of intraindividual bladder changes, in association with cone-beam CT or ultrasonography, is promising. Drinking protocols, diet and laxatives were used in most cases to minimize large variations in bladder size and shape. IGRT is crucial for avoiding tumor undercoverage and undue toxicity during radiation therapy for bladder cancer. IGRT-based adaptive radiation therapy can be performed using cone-beam CT or ultrasonography: modeling of bladder changes with cine-MRI or other imaging techniques might also be useful for facilitating adaptive radiation therapy with personalized margins. PMID- 22064643 TI - Pediatrics: AAP recommends reduced imaging after first febrile UTI. PMID- 22064644 TI - 4-(4-Bromo-phen-yl)-2-oxo-1,2,5,6-tetra-hydro-benzo[h]quinoline-3-carbonitrile. AB - In the mol-ecule of the title compound, C(20)H(13)BrN(2)O, the tetra-hydro benzo[h]quinoline fused-ring system is buckled owing to the ethyl-ene -CH(2)CH(2) fragment, the benzene ring and the pyridine ring being twisted by 17.7 (1) degrees . The 4-substituted aromatic ring is bent away from the pyridine ring by 82.3 (1) degrees in order to avoid crowding the cyanide substituent. Two mol ecules are linked by a pair of N-H?O hydrogen bonds to form a centrosymmetric dimer. PMID- 22064645 TI - Dimethyl 4-(4-hy-droxy-phen-yl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxyl ate. AB - The title mol-ecule, C(17)H(19)NO(5), was prepared by a Hantzsch dihydro-pyridine synthesis from 4-hy-droxy-benzaldehyde, methyl acetoacetate and NH(4)HCO(3). In the mol-ecular structure of the title compound, the dihydro-pyridine ring adopts a flattened boat conformation and the plane of the base of the boat forms a dihedral angle of 80.8 (2) degrees with the aromatic six-membered ring. The packing is stabilized by strong inter-molecular N-H?O(carbon-yl), O(hydrox-y) H?O(carbon-yl) and weak intra-molecular C-H?O hydrogen bonds. PMID- 22064646 TI - {N,N-Bis[2-(diphenyl-phosphan-yl)eth-yl]-aniline}(eta-dibenzyl-ideneacetone) palladium(0). AB - In the title complex, [Pd(C(34)H(33)NP(2))(C(17)H(14)O)], the Pd(0) atom is coordinated in a trigonal planar geometry formed by two P atoms of a bis [(diphenyl-phosphino)eth-yl]aniline ligand and a C=C (eta(2)) bond involving the C atoms that are in the alpha,beta positions relative to the central ketone of the dibenzyl-ideneacetone ligand. PMID- 22064647 TI - N'-[(E)-1-(4-Bromo-phen-yl)ethyl-idene]-4-hy-droxy-2-methyl-1,1-dioxo-2H-1,2 benzothia-zine-3-carbohydrazide. AB - The six-membered heterocycle in the title compound, C(18)H(16)BrN(3)O(4)S, adopts a sofa conformation. Intra-molecular N-H?N and O-H?O hydrogen bonds stabilize the mol-ecular conformation by forming a five- and a six-membered ring, respectively. The crystal packing is stabilized by inter-molecular C-H?O hydrogen bonds. PMID- 22064648 TI - MIC-1 (a multifunctional modulator of dendritic cell phenotype and function) is produced by decidual stromal cells and trophoblasts. AB - BACKGROUND: Macrophage inhibitory cytokine-1 (MIC-1) is a multifunctional cytokine produced in high amounts by placental tissue. Inhibiting trophoblast invasion and suppressing inflammation through inhibition of macrophage activation, MIC-1 is thought to provide pleiotropic functions in the establishment and maintenance of pregnancy. So far, little is known about the decidual cell subsets producing MIC-1 and the effect of this cytokine on dendritic cells (DCs), which are known to play a distinct role in the development of pro-fetal tolerance in pregnancy. METHODS: To identify the decidual cell types expressing and secreting MIC-1, immunohistochemical staining, PCR experiments, western blot analysis and ELISAs were performed. Immature DCs (iDCs) were generated from peripheral blood-derived monocytes and differentiated in the presence of MIC-1 or dexamethasone (Dex) for control. Migratory and proliferative activity of DCs after MIC-1 exposure was investigated by migration and proliferation assay. Cytokine secretion after MIC-1 exposure was tested in isolated uNK cells, isolated CD14+ monocytes, monocyte-derived iDCs and mature DCs. Subsequently, the phenotype of DCs was studied using FACS analysis. To test the T-cell stimulatory capacity of pre-incubated DCs, mixed lymphocyte reaction was applied. Finally, the expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) after the exposure of MIC-1 to maturing DCs was analysed by western blot. RESULTS: Immunohistochemical staining, PCR and western blot experiments demonstrated that MIC-1 is mainly expressed by trophoblast cells and decidual stromal cells. Analysis of the MIC-1 secretion of decidual cell types by ELISA again characterized trophoblast and stromal cells as main producers. The migratory activity of iDCs was significantly induced by MIC-1. No changes in proliferative activity of DCs were observed after MIC-1 pre incubation. The secretion of pro- or anti-inflammatory cytokines was not affected significantly by MIC-1. Studying the phenotype of DCs after MIC-1 exposure by FACS analysis, we observed that MIC-1 suppresses the expression of typical maturation molecules such as CD25 and CD83 as well as of CD86 during cytokine induced DC maturation similar to Dex. In addition, T-cell stimulatory capacity of DCs was significantly reduced after MIC-1 exposure. MIC-1 was also able to increase slightly the expression of IDO (a key immunomodulatory enzyme promoting periphereal tolerance) in maturing DCs. CONCLUSIONS: We have identified MIC-1 as a novel factor (secreted by decidual cells in early pregnancy) that could promote the increase of a tolerogenic subtype of DC in decidua. PMID- 22064649 TI - First experiences with hysterosalpingo-foam sonography (HyFoSy) for office tubal patency testing. AB - BACKGROUND: This study was conducted to describe the first experiences with hysterosalpingo-foam sonography (HyFoSy) as a first step routine office procedure for tubal patency testing. METHODS: A prospective observational cohort study was started in a university affiliated teaching hospital. In 2010, 73 patients with subfertility and a low risk of tubal pathology were examined. A non-toxic foam containing hydroxymethylcellulose and glycerol was applicated through a cervical applicator for contrast sonography (HyFoSy). Tubal patency was determined by transvaginal ultrasonographic demonstration of echogenic dispersion of foam in the Fallopian tube and/or the peritoneal cavity. Only in case patency could not be demonstrated, a hysterosalpingography (HSG) was performed as a control. RESULTS: In 67 out of 73 (92%) patients, a successful procedure was performed. In 57 out of 73 (78%) cases, there was no further need for a HSG. In five patients (5/73; 7%) tubal occlusion was confirmed by HSG and in five patients (5/73; 7%) there was discordance between HyFoSy and HSG. Of 73 patients, 14 (19%) conceived within a median of 3 months after the procedure. CONCLUSIONS: HyFoSy is a successful procedure to demonstrate tubal patency as a first step office procedure. PMID- 22064650 TI - The risk of stroke in patients with acute myocardial infarction treated invasively. AB - BACKGROUND: To assess the incidence, clinical significance, and independent risk factors of stroke in patients with acute myocardial infarction (AMI) treated invasively. MATERIALS AND METHODS: We analyzed 2520 consecutive patients with AMI admitted between 2003 and 2007. Data on long-term follow-up were screened to identify patients who had stroke. RESULTS: During a median of 25.5 months, 52 patients (2.07%) had stroke. The cumulative risk of stroke was the highest during the first year (1.23%) and particularly within the first month after AMI (0.28%). Patients with stroke were at a significantly higher risk of developing major adverse cardiovascular events, including repeated AMI (26.9 vs. 14.6%, P<0.05) and death (40.4 vs. 13.6%, P<0.001). Previous stroke [hazard ratio (HR) 5.89], female sex (HR 2.60), glomerular filtration rate <60 ml/min/1.73 m (HR 1.92), and contrast nephropathy (HR 1.87, all P<0.05) were independent predictors of stroke. The receiver-operating curve calculated for the Contrast nephropathy, renal Insufficiency, Female, prior Stroke (CIFS) risk scale demonstrated a significant predictive value of this scale (area under curve 0.73, P<0.001). Patients with the lowest, median, and highest risk scores (<4, 4-5, >=6 points, respectively) differed significantly with regard to stroke incidence (2.1 vs. 7.9 vs. 14.0%, respectively, P<0.05). CONCLUSION: The risk of stroke is the highest within the first month after AMI. Stroke is a marker of unfavorable outcome in this population. Independent risk factors for stroke after invasive treatment of AMI are different from those commonly perceived as stroke predictors. A risk scale based on sex, stroke history, and renal impairment is useful in risk stratification. PMID- 22064651 TI - Aortopulmonary fistula in acute dissection: findings at unenhanced and enhanced computed tomographic imaging. AB - Acquired aortopulmonary fistulas are a rare complication of acute aortic dissections. We present a case of an aortopulmonary fistula after a Stanford type A dissection, focusing on the imaging findings and etiology of this entity. Early recognition can lead to proper surgical planning and increase the chance of survival. PMID- 22064652 TI - MiR-126 acts as a tumor suppressor in pancreatic cancer cells via the regulation of ADAM9. AB - The epithelial-mesenchymal transition (EMT) is a critical step for pancreatic cancer cells as an entry of metastatic disease. Wide variety of cytokines and signaling pathways are involved in this complex process while the entire picture is still cryptic. Recently, miRNA was found to regulate cellular function including EMT by targeting multiple mRNAs. We conducted comprehensive analysis of miRNA expression profiles in invasive ductal adenocarcinoma (IDA), intraductal papillary mucinous adenoma, intraductal papillary mucinous carcinoma, and human pancreatic cancer cell line to elucidate essential miRNAs which regulate invasive growth of pancreatic cancer cells. Along with higher expression of miR-21 which has been shown to be highly expressed in IDA, reduced expression of miR-126 in IDA and pancreatic cancer cell line was detected. The miR-126 was found to target ADAM9 (disintegrin and metalloproteinase domain-containing protein 9) which is highly expressed in pancreatic cancer. The direct interaction between miR-126 and ADAM9 mRNA was confirmed by 3' untranslated region assay. Reexpression of miR-126 and siRNA-based knockdown of ADAM9 in pancreatic cancer cells resulted in reduced cellular migration, invasion, and induction of epithelial marker E-cadherin. We showed for the first time that the miR-126/ADAM9 axis plays essential role in the inhibition of invasive growth of pancreatic cancer cells. PMID- 22064653 TI - Silencing of DLC1 upregulates PAI-1 expression and reduces migration in normal prostate cells. AB - Deleted in liver cancer 1 (DLC1) is a GTPase-activating protein (GAP) domain containing tumor suppressor that localizes to focal adhesions. In cancer cells, loss of DLC1 is known to enhance cancer cell migration. However, the role of DLC1 in normal cell migration has not been well studied. Here, we show that silencing of DLC1 (shDLC1) in normal prostate epithelial cells reduces cell migration in both Transwell and wound-healing assays. This migration defect is mainly due to upregulation of plasminogen activator inhibitor 1 (PAI-1). Silencing of PAI-1 rescues the shDLC1-reduced migration phenotype. Reexpression of DLC1 suppresses PAI-1 and restores the migration defect as well. In contrast, DLC1-K714E (GAP inactive) mutant neither decreases the PAI-1 level nor rescues the shDLC1 migration defect. Interestingly, DLC1-Y442F (tensin-binding and focal adhesion localizing defective) mutant is able to suppress PAI-1 expression but does not restore the migration defect. Furthermore, PAI-1 upregulation in shDLC1 cells is EGFR-MEK pathway dependent and is able to promote in vitro angiogenesis. Together, our results show that at least the following two new mechanisms are involved in DLC1-mediated normal cell migration: (i) DLC1 modulates the expression of PAI-1, which is a negative regulator for cell migration, in a GAP domain and EGFR-MEK-dependent manner and (ii) Independent of PAI-1, the interaction of DLC1 with tensin members positively regulates cell migration. PMID- 22064654 TI - Genetic and epigenetic inactivation of extracellular superoxide dismutase promotes an invasive phenotype in human lung cancer by disrupting ECM homeostasis. AB - Extracellular superoxide dismutase (EcSOD) is an important superoxide scavenger in the lung in which its loss, sequence variation, or abnormal expression contributes to lung diseases; however, the role of EcSOD in lung cancer has yet to be studied. We hypothesized that EcSOD loss could affect malignant progression in lung, and could be either genetic or epigenetic in nature. To test this, we analyzed EcSOD expression, gene copy number, promoter methylation, and chromatin accessibility in normal lung and carcinoma cells. We found that normal airway epithelial cells expressed abundant EcSOD and had an unmethylated promoter, whereas EcSOD-negative lung cancer cells displayed aberrant promoter hypermethylation and decreased chromatin accessibility. 5-aza-dC induced EcSOD suggesting that cytosine methylation was causal, in part, to silencing. In 48/50 lung tumors, EcSOD mRNA was significantly lower as early as stage I, and the EcSOD promoter was hypermethylated in 8/10 (80%) adenocarcinomas compared with 0/5 normal lung samples. In addition, 20% of the tumors showed loss of heterozygosity (LOH) of EcSOD. Reexpression of EcSOD attenuated the malignant phenotype of lung carcinoma cells by significantly decreasing invasion and survival. Finally, EcSOD decreased heparanase and syndecan-1 mRNAs in part by reducing NF-kappaB. By contrast, MnSOD and CuZnSOD showed no significant changes in lung tumors and had no effect on heparanase expression. Taken together, the loss of EcSOD expression is unique among the superoxide dismutases in lung cancer and is the result of EcSOD promoter methylation and LOH, suggesting that its early loss may contribute to ECM remodeling and malignant progression. PMID- 22064655 TI - Activation of androgen receptor, lipogenesis, and oxidative stress converged by SREBP-1 is responsible for regulating growth and progression of prostate cancer cells. AB - We previously reported that sterol regulatory element-binding protein-1 (SREBP-1) is involved in the transcriptional regulation of androgen receptor (AR) and formation of fatty acid through altered expression of fatty acid synthase (FASN). In this article, we provide a new finding that SREBP-1 induced oxidative stress in prostate cancer cells through increased production of reactive oxygen species (ROS) and expression of NADPH oxidase 5 (Nox5). We have shown that (i) expression of SREBP-1 protein is positively associated with the clinical Gleason grades in human prostate cancer; (ii) genetic overexpression or knockdown of SREBP-1 in prostate cancer cells resulted in corresponding increased or decreased AR, FASN and Nox5 expression, fatty acid and lipid droplet accumulation, and ROS generation; and (iii) SREBP-1 induces and promotes the growth, migration, invasion, and castration-resistant progression of prostate cancer cells in vitro and in vivo. Our data show a novel molecular mechanism by which SREBP-1 promotes prostate cancer growth and progression through alterations in the concerted intracellular metabolic and signaling networks involving AR, lipogenesis, and ROS in prostate cancer cells. PMID- 22064656 TI - Fractalkine receptor CX(3)CR1 is expressed in epithelial ovarian carcinoma cells and required for motility and adhesion to peritoneal mesothelial cells. AB - Epithelial ovarian carcinoma (EOC) is a deadly disease, and little is known about the mechanisms underlying its metastatic progression. Using human specimens and established cell lines, we determined that the G-protein-coupled seven transmembrane fractalkine receptor (CX(3)CR1) is expressed in primary and metastatic ovarian carcinoma cells. Ovarian carcinoma cells robustly migrated toward CX(3)CL1, a specific ligand of CX(3)CR1, in a CX(3)CR1-dependent manner. Silencing of CX(3)CR1 reduced migration toward human ovarian carcinoma ascites fluid by approximately 70%. Importantly, adhesion of ovarian carcinoma cells to human peritoneal mesothelial cells was dependent on CX(3)CL1/CX(3)CR1 signaling. In addition, CX(3)CL1 was able to induce cellular proliferation. Together, our data suggest that the fractalkine network may function as a major contributor to the progression of EOC, and further attention to its role in the metastasis of this deadly malignancy is warranted. PMID- 22064657 TI - Regulation of CXCL8/IL-8 expression by zonula occludens-1 in human breast cancer cells. AB - Accumulating data now suggest that ZO-1, once delocalized from tight junctions, could be implicated in the regulation of tumor-promoting genes. Because of their major implication in different steps of tumor progression, we investigated here the influence of ZO-1 on chemokines expression in breast cancer cells. Using GeneArray analysis to compare chemokine mRNA expression in breast tumor cells transfected with a siRNA against ZO-1, we identified CXCL-8IL-8 as a major potential target of ZO-1 signaling, being strongly downregulated following ZO-1 siRNA transfection. Examining further the relationship between ZO-1 and interleukin-8 (CXCL8/IL-8), we first showed that CXCL8/IL-8 expression correlates with a relocalization of ZO-1 in several breast cancer cell lines. Moreover, CXCL8/IL-8 is downregulated in invasive BT549 cells transfected with three different ZO-1 siRNA and overexpressed in noninvasive BT20 and SKBR3 cells transfected with vectors expressing ZO-1. We also provide evidence for an activation of the CXCL8/IL-8 promoter by ZO-1. Finally, we show that the regulation of CXCL8/IL-8 by ZO-1 is independent of the beta-catenin pathway. Our results thus clearly show an implication of ZO-1 in CXCL8/IL-8 regulation. Because of the major implications of CXCL8/IL-8 in tumor invasion, such a regulation could play an important role in breast cancer progression. PMID- 22064658 TI - Lung cancer in mice induced by the jaagsiekte sheep retrovirus envelope protein is not maintained by rare cancer stem cells, but tumorigenicity does correlate with Wnt pathway activation. AB - JSRV, a simple beta-retrovirus, is the etiologic agent of ovine pulmonary adenocarcinoma, a form of non-small cell lung cancer in sheep and goats. It has been shown that the envelope protein alone is sufficient to induce tumorigenesis in the lungs of mice when delivered via an adeno-associated viral vector. Here, we tested the hypothesis that JSRV envelope-induced tumors are maintained by a small population of tumor-initiating cells, termed cancer stem cells. To test this hypothesis, dissociated cancer cells were sorted from envelope-induced tumors in mouse lung based on the putative stem cell markers Sca-1, CD34, and CD133, the pluripotency-associated transcription factor Oct4, and the level of Wnt signaling. No association with increased tumor-initiating capacity was found with any of the cell-surface markers. In addition, we were unable to detect any evidence of Oct4 expression in tumor-bearing mouse lung. However, tumor cells possessing an active Wnt signaling pathway did show a significant correlation with increased tumor formation upon transplantation. Limiting dilution transplant analysis suggests the existence of a large fraction of cells with the ability to propagate tumor growth, with increasing tumor initiation potential correlating with activated Wnt signaling. PMID- 22064660 TI - MRI in acute and subacute post-traumatic spinal cord injury: pictorial review. AB - STUDY DESIGN: Pictorial review. OBJECTIVES: To illustrate MRI signs of acute and subacute injury with emphasis on evidence-based links to clinical outcome and implications for treatment. METHODS: Description of important aspects of MRI techniques and illustration of critical MRI signs important in the assessment of spinal cord injury following trauma, in the acute and subacute stages. CONCLUSIONS: Familiarity with cord MRI appearances has an important impact on planning the management of the acutely spinal cord injured patient and also identifying complications in the subacute phase particularly in the presence of neurological deterioration. PMID- 22064661 TI - The translational dialogue in spinal cord injury research. AB - BACKGROUND: Although the emphasis in clinical spinal cord injury (SCI) research has been directed towards the evaluation of clinical assessments (standards in neurological examination) and the appreciation of outcome measures (that is, extent and pattern of clinical recovery from SCI), the underlying neurological mechanisms for recovery from SCI are not well documented in humans. However, to improve the translational research, a meaningful preclinical-clinical dialogue is required, with an appreciation for both fundamental neural mechanisms and what makes human SCI unique. This holds true both for potential interventions in rehabilitation and novel drug or cell-based treatment approaches in acute SCI. OBJECTIVES: The gap in translational research that needs to be approached from both ends not only includes the appreciation of principal neural mechanisms (repair, sprouting, plasticity) and their assumed impact onto outcomes (even though humans and non primate animals may rely on slightly different supraspinal control for some movements), but also includes an understanding of the spatial (location and size of lesion) and temporal (timelines of damage and recovery) factors in spinal cord damage that can vary considerably between the different species being studied. CONCLUSION: The preclinical-clinical dialogue should be encouraged as a venue to improve the appreciation of discoveries in basic research, and to power valid discoveries towards a meaningful translation into advanced treatments downstream. Similarly, the upstream identification of appropriate clinical targets that take into account clinical constraints depends on reliable and advanced clinical information being provided to preclinical investigators. PMID- 22064662 TI - Visualization of DNA replication in the vertebrate model system DT40 using the DNA fiber technique. AB - Maintenance of replication fork stability is of utmost importance for dividing cells to preserve viability and prevent disease. The processes involved not only ensure faithful genome duplication in the face of endogenous and exogenous DNA damage but also prevent genomic instability, a recognized causative factor in tumor development. Here, we describe a simple and cost-effective fluorescence microscopy-based method to visualize DNA replication in the avian B-cell line DT40. This cell line provides a powerful tool to investigate protein function in vivo by reverse genetics in vertebrate cells(1). DNA fiber fluorography in DT40 cells lacking a specific gene allows one to elucidate the function of this gene product in DNA replication and genome stability. Traditional methods to analyze replication fork dynamics in vertebrate cells rely on measuring the overall rate of DNA synthesis in a population of pulse-labeled cells. This is a quantitative approach and does not allow for qualitative analysis of parameters that influence DNA synthesis. In contrast, the rate of movement of active forks can be followed directly when using the DNA fiber technique(2-4). In this approach, nascent DNA is labeled in vivo by incorporation of halogenated nucleotides (Fig 1A). Subsequently, individual fibers are stretched onto a microscope slide, and the labeled DNA replication tracts are stained with specific antibodies and visualized by fluorescence microscopy (Fig 1B). Initiation of replication as well as fork directionality is determined by the consecutive use of two differently modified analogues. Furthermore, the dual-labeling approach allows for quantitative analysis of parameters that influence DNA synthesis during the S phase, i.e. replication structures such as ongoing and stalled forks, replication origin density as well as fork terminations. Finally, the experimental procedure can be accomplished within a day, and requires only general laboratory equipment and a fluorescence microscope. PMID- 22064664 TI - Cortical systems that process language, as revealed by non-native speech sound perception. AB - Over the course of language acquisition, the brain becomes specialized in the perception of native language speech sounds or phonemes. As a result, adult speakers are highly efficient at processing their native language, but may struggle to perceive some non-native phonemes. This specialization is thought to arise from changes that occur in a person's brain as a result of maturation and language experience. In this study, adult native speakers of English were asked to discriminate between phonemes of varying degrees of difference from English (similar to English: Tagalog /na/-/na/; different from English: Ndebele /k||i/ /k!i/), as their brain activity was measured using functional near infrared spectroscopy imaging. The left inferior frontal region showed activation only during the native condition; this finding is discussed in the context of developmental and adult neuroimaging work and suggests that the left inferior frontal region is critical for perceiving native phoneme contrasts during development and in adulthood. PMID- 22064665 TI - 3-[4-(2-Chloro-benzyl-idene-amino)-3-methyl-5-sulfanyl-idene-4,5-dihydro-1H-1,2,4 triazol-1-yl]-1,3-diphenyl-propan-1-one. AB - In the title mol-ecule, C(25)H(21)ClN(4)OS, the triazole ring forms dihedral angles of 47.9 (2), 84.5 (2) and 3.9 (2) degrees with the two phenyl rings and the chloro-phenyl ring, respectively. The chloro-phenyl ring, the triazole ring and the conjugative linker between the two aromatic rings are nearly coplanar with an r.m.s. deviation of 0.0483 (2) A and a maximum deviation of 0.0911 (2) A. PMID- 22064666 TI - Endothelial nitric oxide synthase genotypes and haplotypes modify the responses to sildenafil in patients with erectile dysfunction. AB - Erectile dysfunction (ED) is usually treated with sildenafil. Although genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may impair endogenous NO formation, there is little information about how eNOS polymorphisms and haplotypes affect the responses to sildenafil. We studied 118 patients; 63 patients had ED secondary to radical prostatectomy (PED) and 55 had organic, clinical ED. eNOS genotypes for three eNOS polymorphisms (T(-786)C, rs2070744; a variable number of tandem repeats (VNTR) in intron 4; and Glu298Asp, rs1799983) were determined, and eNOS haplotypes were estimated using PHASE 2.1. The clinical responses to sildenafil were evaluated and the patients were classified as good responders (GR) or poor responders (PR) when their changes in five-item version of International Index for Erectile Function questionnaire were above or below the median value. The TC/CC genotypes and the C allele for the T(-786)C polymorphism were more common in GR, compared with PR patients with PED. However, the 4b4a/4a4a genotypes and the 4a allele for the VNTR polymorphism in intron 4 were more common in GR, compared with PR patients with clinical ED. The C-4a-Glu haplotype was more common in GR than in PR patients with PED. Conversely, the T 4b-Asp haplotype was less common in GR than in PR patients with PED. No other significant differences were found. Our findings show evidence that eNOS polymorphisms affect the responses of PED and clinical ED patients to sildenafil. PMID- 22064667 TI - Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. AB - BACKGROUND: Hirsutism, defined by the presence of excessive terminal hair in androgen-sensitive areas of the female body, is one of the most common disorders in women during reproductive age. METHODS: We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, pathophysiology, diagnosis and management of hirsutism. RESULTS: The prevalence of hirsutism is ~10% in most populations, with the important exception of Far East Asian women who present hirsutism less frequently. Although usually caused by relatively benign functional conditions, with the polycystic ovary syndrome leading the list of the most frequent etiologies, hirsutism may be the presenting symptom of a life-threatening tumor requiring immediate intervention. CONCLUSIONS: Following evidence-based diagnostic and treatment strategies that address not only the amelioration of hirsutism but also the treatment of the underlying etiology is essential for the proper management of affected women, especially considering that hirsutism is, in most cases, a chronic disorder needing long-term follow-up. Accordingly, we provide evidence-based guidelines for the etiological diagnosis and for the management of this frequent medical complaint. PMID- 22064668 TI - Thromboxane A2 receptor: biology and function of a peculiar receptor that remains resistant for therapeutic targeting. AB - While blood platelets express several G-protein-coupled receptors (GPCRs) that play pivotal roles in their activation, several diseases, for example thrombotic disorders, may develop if these receptors are inappropriately activated. Thus, these receptors have been the subject of investigations to design therapeutic interventions for managing multiple thrombosis-based disease states. One such GPCR, the thromboxane A(2) receptor (TPR), remains resistant to such interventions. The present review provides a critical examination of the binding, structural biology, and signaling of TPRs. The review also provides a rationale for using principles of "drug rediscovery" as an alternative/viable approach for the therapeutic targeting of TPRs. To this end, it is noteworthy that many US Food and Drug Administration (FDA)-approved drugs have been found to selectively (and nonselectively) block TPR-mediated functional responses, for example platelet aggregation, as described in this review. Therefore, while none of the antagonists, thus far developed for targeting TPRs, have made it into clinical use, this peculiar receptor can be antagonized by a large number of drugs used for indications unrelated to thrombosis. PMID- 22064669 TI - Efficient derivation of human neuronal progenitors and neurons from pluripotent human embryonic stem cells with small molecule induction. AB - There is a large unfulfilled need for a clinically-suitable human neuronal cell source for repair or regeneration of the damaged central nervous system (CNS) structure and circuitry in today's healthcare industry. Cell-based therapies hold great promise to restore the lost nerve tissue and function for CNS disorders. However, cell therapies based on CNS-derived neural stem cells have encountered supply restriction and difficulty to use in the clinical setting due to their limited expansion ability in culture and failing plasticity after extensive passaging(1-3). Despite some beneficial outcomes, the CNS-derived human neural stem cells (hNSCs) appear to exert their therapeutic effects primarily by their non-neuronal progenies through producing trophic and neuroprotective molecules to rescue the endogenous cells(1-3). Alternatively, pluripotent human embryonic stem cells (hESCs) proffer cures for a wide range of neurological disorders by supplying the diversity of human neuronal cell types in the developing CNS for regeneration(1,4-7). However, how to channel the wide differentiation potential of pluripotent hESCs efficiently and predictably to a desired phenotype has been a major challenge for both developmental study and clinical translation. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, resulting in inefficient and uncontrollable lineage-commitment that is often followed by phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity(7-10). In addition, undefined foreign/animal biological supplements and/or feeders that have typically been used for the isolation, expansion, and differentiation of hESCs may make direct use of such cell-specialized grafts in patients problematic(11-13). To overcome these obstacles, we have resolved the elements of a defined culture system necessary and sufficient for sustaining the epiblast pluripotence of hESCs, serving as a platform for de novo derivation of clinically suitable hESCs and effectively directing such hESCs uniformly towards clinically relevant lineages by small molecules(14) (please see a schematic in Fig. 1). Retinoic acid (RA) does not induce neuronal differentiation of undifferentiated hESCs maintained on feeders(1, 14). And unlike mouse ESCs, treating hESC differentiated embryoid bodies (EBs) only slightly increases the low yield of neurons(1, 14, 15). However, after screening a variety of small molecules and growth factors, we found that such defined conditions rendered retinoic acid (RA) sufficient to induce the specification of neuroectoderm direct from pluripotent hESCs that further progressed to neuroblasts that generated human neuronal progenitors and neurons in the developing CNS with high efficiency (Fig. 2). We defined conditions for induction of neuroblasts direct from pluripotent hESCs without an intervening multi-lineage embryoid body stage, enabling well controlled efficient derivation of a large supply of human neuronal cells across the spectrum of developmental stages for cell-based therapeutics. PMID- 22064670 TI - Dynamic changes in the inner ear function and vestibular neural pathway related to the progression of labyrinthine infarction in patient with an anterior inferior cerebellar artery infarction. AB - OBJECTIVE: To describe changes in the inner ear function and the vestibular neural pathway according to the progression of a labyrinthine infarction in a patient with an anterior inferior cerebellar artery (AICA) infarction. PATIENT: A 58-year-old woman with hypertension who presented with isolated inner ear symptoms similar to those of endolymphatic hydrops but finally progressed to an AICA infarction. INTERVENTION: Serial neurotologic testing according to progression to an AICA infarction and antiplatelet therapy. MAIN OUTCOME MEASURES: Radiologic findings and neurotologic parameters, including pure tone audiogram thresholds, spontaneous nystagmus, summating potentials/action potentials on electrocochleography, interaural amplitude difference on the vestibular-evoked myogenic potential test, canal paresis and fixation index on the bithermal caloric test, and gain on oculomotor tests. RESULTS: Our patient initially presented with sudden hearing loss and was diagnosed with an acute AICA infarction on a follow up MRI. Dynamic change in neurotologic testing was observed during disease progression. The vertigo and motion intolerance improved gradually after antiplatelet therapy. CONCLUSION: Changes in the clinical profile, which were documented during a transition from isolated labyrinthine ischemia to an AICA infarction, suggest that sensitivity to an ischemic injury is variable in different components of the labyrinthine organs in addition to providing a new insight into the response of vestibular neural pathway to ischemic injury. PMID- 22064671 TI - Intracochlear visualization: comparing established and novel endoscopy techniques. AB - HYPOTHESIS: Intracochlear visualization is achievable with chip-on-tip endoscopes also called (digital) video endoscopy, videoscopy, electronic endoscopy, or endoscopy with distal chip/sensor/camera technology. BACKGROUND: Recent advances in digital camera sensor sizes have significantly reduced the size of chip-on-tip endoscopes to sizes near that of the scala tympani opening up the possibility of intracochlear visualization. METHODS: We compared the image quality of chip-on tip cameras with commercially available rigid endoscopes (a.k.a. Hopkins rods) and commercially available fiber-optic scopes (sialendoscopes). Furthermore, we performed a feasibility study to elucidate the spatial constraints that future visualization technology must reach to allow intracochlear visualization. RESULTS: Image resolution for chip-on-tip endoscopes ranks before fiberscopes and after Hopkins rods. The image quality depends further on illumination, which remains unresolved for chip-on-tip endoscopes for intracochlear visualization. The insertion depth of the currently available cameras allows up to 270 degrees of travel from the round window. CONCLUSION: Visual guidance and inspection inside scala tympani is possible with a novel, small-sized digital camera endoscope. This may find clinical applicability for visual confirmation of anatomy during cochlear implantation. PMID- 22064672 TI - Investigating the association between polymorphism of follicle-stimulating hormone receptor gene and ovarian response in controlled ovarian hyperstimulation. AB - AIM: The aim of the study was to investigate the association between follicle stimulating hormone receptor (FSHR) gene polymorphism at Position 680 and the outcomes of controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer (IVF-ET) in infertile women. MATERIALS AND METHODS: One hundred and eight patients under 35 years of age who underwent IVF-ET procedures were included in this study. The hormonal profile and treatment of all patients were analyzed and FSHR polymorphism was examined by polymerase chain reaction restriction fragment length polymorphism. Women from all groups were classified based on polymorphisms at Position 680, occupied either by asparagines (Asn) or serine (Ser) as Asn/Asn, Asn/Ser, and Ser/Ser genotype. RESULT: Our study showed that all patients in the Asn/Asn group were normal responders and in the Asn/Ser group 64.8% were normal responders and 21.1% and 14.1% were poor and hyper responders respectively. In the Ser/Ser group we did not have normal responders and 46.7% of these patients were poor responders and 53.3% were hyper responders. CONCLUSION: FSH receptor polymorphism is correlated with response to ovarian stimulation. PMID- 22064673 TI - Sudden hearing loss in sarcoidosis: otoneurological study and neuroradiological correlates. AB - Sarcoidosis is an inflammatory multisystem disorder of unknown cause. Approximately 5-7% of patients manifest symptoms of central nervous system involvement, or neurosarcoidosis. Cranial neuropathy usually entails facial nerve palsy and optic neuritis. Sudden hearing loss has been reported in fewer than 20 cases. Herewith, two new cases of sudden hearing loss due to probable neurosarcoidosis are reported, each having a quite different clinical course. In one case, unilateral sudden hearing loss and facial palsy were the presenting symptoms of systemic sarcoidosis, while in the second, unilateral sudden deafness occurred despite ongoing immunosuppressive treatment for systemic sarcoidosis. PMID- 22064674 TI - A model for rural psychiatric services-raipur rani experience. AB - During the last five years efforts have been directed to understand the needs of the mentally ill persons residing in the rural areas. An outcome of our work involving 60,000 people living in a geographically defined area in Ambala District of Haryana has resulted in a realistic model for wider application in the country. The project work has led to the development of a number of research instruments and data regarding the prevalence of mental illness in the rural areas. A method for identifying mentally ill and to study the community attitudes has also been developed. The preparation of the Manual and simple training programmes has been a significant contribution. Knowledge regarding the practical problems of supervision and support of peripheral health workers in carrying out mental health work has been gained. The formation of the Mental Health Association by the village leaders has enhanced the community awareness and involvement in the ongoing programme of care.It is hoped that the experiences and the results of the above research work would act as a stimulant for similar experiments and further refining of the needed expertise and data for making mental health care a reality at the primary health care in the near future. PMID- 22064675 TI - Opipramolium fumarate. AB - In the crystal structure of the title salt {systematic name: 4-[3-(5H dibenz[b,f]azepin-5-yl)prop-yl]-1-(2-hy-droxy-eth-yl)piperazin-1-ium (2Z)-3-carb oxy-prop-2-enoate}, C(23)H(30)N(3)O(+).C(4)H(3)O(4) (-), the piperazine group in the opipramol cation is protonated at only one of the N atoms. In the cation, the dihedral angle between the two benzene rings is 53.5 (6) degrees . An extensive array of inter-molecular O-H?O, O-H?N and N-H?O hydrogen bonds and weak inter molecular N-H?O, C-H?O and C-H?pi inter-actions dominate the crystal packing. PMID- 22064676 TI - 6,7,6',7'-Tetra-phenyl-2,2'-bi[1,3-dithia-5,8-diaza-cyclo-penta-[b]naphthalenyl idene] chloro-form disolvate. AB - The title compound, C(42)H(24)N(4)S(4).2CHCl(3), a symmetrical tetra-thia fulvalene (TTF) derivative, was prepared by a tri-ethyl-phos-phite-mediated self coupling reaction of 6,7-diphenyl-1,3-dithia-5,8-diaza-cyclo-penta-[b]napthalen-2 one. The asymmetric unit contains two TTF mol-ecules and four chloro-form solvent mol-ecules. Cl?Cl inter-actions [contact distances = 3.263 (1)-3.395 (2) A] are present between the solvent mol-ecules, resulting in a tape along the bc plane. The crystal packing features weak C-H?Cl and C-H?N hydrogen bonds, resulting in the formation of a two-dimensional supramolecular network. PMID- 22064677 TI - Specificity determinants of allosteric modulation in the neuronal nicotinic acetylcholine receptor: a fine line between inhibition and potentiation. AB - We are interested in the allosteric modulation of neuronal nicotinic acetylcholine receptors (nAChRs). We have postulated that the anthelmintic morantel (Mor) positively modulates (potentiates) rat alpha3beta2 receptors through a site located at the beta(+)/alpha(-) interface that is homologous to the canonical agonist site (J Neurosci 29:8734-8742, 2009). On this basis, we aimed to determine the site specificity by studying differences in modulation between alpha3beta2 and alpha4beta2 receptors. We also compared modulation by Mor with that of the related compound oxantel (Oxa). Whereas Mor and Oxa each potentiated alpha3beta2 receptors 2-fold at saturating acetylcholine (ACh) concentrations, Mor had no effect on alpha4beta2 receptors, and Oxa inhibited ACh evoked responses. The inhibition was noncompetitive, but not due to open channel block. Furthermore, the nature and extent of modulation did not depend on subunit stoichiometry. We studied six positions at the alpha(-) interface that differ between alpha3 and alpha4. Two positions (alpha3Ile57 and alpha3Thr115) help mediate the effects of the modulators but do not seem to contribute to specificity. Mutations in two others (alpha3Leu107 and alpha3Ile117) yielded receptors with appreciable alpha4-character; that is, Mor potentiation was reduced compared with wild-type alpha3beta2 control and Oxa inhibition was evident. A fifth position (alpha3Glu113) was unique in that it discriminated between the two compounds, showing no change in Mor potentiation from control but substantial Oxa inhibition. Our work has implications for rational drug design for nicotinic receptors and sheds light on mechanisms of allosteric modulation in nAChRs, especially the subtle differences between potentiation and inhibition. PMID- 22064678 TI - Functional selectivity in CB(2) cannabinoid receptor signaling and regulation: implications for the therapeutic potential of CB(2) ligands. AB - Receptor internalization increases the flexibility and scope of G protein-coupled receptor (GPCR) signaling. CB(1) and CB(2) cannabinoid receptors undergo internalization after sustained exposure to agonists. However, it is not known whether different agonists internalize CB(2) to different extents. Because CB(2) is a promising therapeutic target, understanding its trafficking in response to different agonists is necessary for a complete understanding of its biology. Here we profile a number of cannabinoid receptor ligands and provide evidence for marked functional selectivity of cannabinoid receptor internalization. Classic, aminoalkylindole, bicyclic, cannabilactone, iminothiazole cannabinoid, and endocannabinoid ligands varied greatly in their effects on CB(1) and CB(2) trafficking. Our most striking finding was that (R)-(+)-[2,3-dihydro-5-methyl-3 (4-morpholinylmethyl) pyrrolo-[1,2,3-d,e]-1,4-benzoxazin-6-yl]-1-naphthalenyl methanone (WIN55,212-2) (and other aminoalkylindoles) failed to promote CB(2) receptor internalization, whereas 5-(1,1-dimethylheptyl)-2-(5-hydroxy-2-(3 hydroxypropyl)cyclohexyl)phenol (CP55,940) robustly internalized CB(2) receptors. Furthermore, WIN55,212-2 competitively antagonized CP55,940-induced CB(2) internalization. Despite these differences in internalization, both compounds activated CB(2) receptors as measured by extracellular signal-regulated kinase 1/2 phosphorylation and recruitment of beta-arrestin(2) to the membrane. In contrast, whereas CP55,940 inhibited voltage-gated calcium channels via CB(2) receptor activation, WIN55,212-2 was ineffective on its own and antagonized the effects of CP55,940. On the basis of the differences we found between these two ligands, we also tested the effects of other cannabinoids on these signaling pathways and found additional evidence for functional selectivity of CB(2) ligands. These novel data highlight that WIN55,212-2 and other cannabinoids show strong functional selectivity at CB(2) receptors and suggest that different classes of CB(2) ligands may produce diverse physiological effects, emphasizing that each class needs to be separately evaluated for therapeutic efficacy. PMID- 22064679 TI - Zearalenone contamination in barley, corn, silage and wheat bran. AB - Zearalenone (ZEN) is a nonsteroidal estrogen mycotoxin produced by Fusarium graminearum and other Fusarium species, which are plant pathogenic fungi that infect many plants and their products, including corn, barley, fruits and vegetables. This study presents the results of a survey for ZEN contamination on barley, corn, silage and wheat bran. A total of 54 samples were collected from Shahrekord in spring and summer 2010, including 20 barley, 8 corn, 12 silage and 14 wheat bran and analyzed using direct competitive enzyme-linked immunosorbent assay. From 54 samples analyzed, ZEN was found in 8 samples (14.8%), with a mean level of 142 ng/g. Corn had the highest incidence of ZEN (25.0%), followed by barley (20.0%) and silage (16.7%). No ZEN was detected in any wheat bran samples. The results of this study show that ZEN-exposed corn, barley, silage and wheat bran would not be a health concern in animals. PMID- 22064680 TI - Cloning and expression of alkane hydroxylase-1 from Alcanivorax borkumensis in Escherichia coli. AB - Enzymes with hydroxylating activity on alkanes have potential application as biotransformation catalysts in chemical and pharmaceutical industry. Genome of Alcanivorax borkumensis, a marine bacterium with hydrocarbon dissimilation activity, contains at least two P450 monooxygenases and two nonheme monooxygenases, AlkB1 and AlkB2, respectively. Presumably, all these enzymes possess alkane hydroxylating activity. Both AlkB1 and AlkB2 are membrane proteins. Two accessory proteins, rubredoxin and rubredoxin reductase, supply the reducing equivalent from nicotinamide adenine dinucleotide phosphate reduced (NADPH to hydroxylases. Rubredoxin reductase catalyses the reduction of rubredoxin by oxidation of NADPH, and rubredoxin transfers the electrons to the alkane hydroxylase to complete the hydroxylation reaction. Here, we sought to investigate the expression of alkB1 gene in Escherichia coli. Therefore, we amplified alkB1 gene from A. borkumensis genome by polymerase chain reaction and cloned it in the expression vector pET26 upstream of His-tag sequence. Predisposed BL21 (DE3) cells were transformed by the recombinant vector. At last, expression of recombinant enzyme was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting. Regarding the potential ability of this enzyme in hydroxylation of long-chained alkanes, the application of it would be studied in petroleum downstream industries. PMID- 22064681 TI - A weight of evidence approach for the assessment of the ototoxic potential of industrial chemicals. AB - There is accumulating epidemiological evidence that exposure to some solvents, metals, asphyxiants and other substances in humans is associated with an increased risk of acquiring hearing loss. Furthermore, simultaneous and successive exposure to certain chemicals along with noise can increase the susceptibility to noise-induced hearing loss. There are no regulations that require hearing monitoring of workers who are employed at locations in which occupational exposure to potentially ototoxic chemicals occurs in the absence of noise exposure. This project was undertaken to develop a toxicological database allowing the identification of possible ototoxic substances present in the work environment alone or in combination with noise exposure. Critical toxicological data were compiled for chemical substances included in the Quebec occupational health regulation. The data were evaluated only for noise exposure levels that can be encountered in the workplace and for realistic exposure concentrations up to the short-term exposure limit or ceiling value (CV) or 5 times the 8-h time weighted average occupational exposure limit (TWA OEL) for human data and up to 100 times the 8-h TWA OEL or CV for animal studies. In total, 224 studies (in 150 articles of which 44 evaluated the combined exposure to noise and a chemical) covering 29 substances were evaluated using a weight of evidence approach. For the majority of cases where potential ototoxicity was previously proposed, there is a paucity of toxicological data in the primary literature. Human and animal studies indicate that lead, styrene, toluene and trichloroethylene are ototoxic and ethyl benzene, n-hexane and p-xylene are possibly ototoxic at concentrations that are relevant to the occupational setting. Carbon monoxide appears to exacerbate noise-induced hearing dysfunction. Toluene interacts with noise to induce more severe hearing losses than the noise alone. PMID- 22064682 TI - Oxidative damage in erythrocytes of adult rats and their suckling pups exposed to gibberellic acid. AB - Gibberellic acid (GA(3)) is a plant growth regulator used in agriculture worldwide. The present study investigated the propensity of GA(3) to induce hematological disorders. Pregnant Wistar rats were randomly divided into two groups: group I served as controls; group II received orally GA(3) (200 ppm) from the 14th day of pregnancy until day 14 after delivery. GA(3) reduced the number of red blood cells, hemoglobin concentration, and hematocrit in suckling rats, while these parameters remained unchanged in their mothers. White blood cells increased in mothers and were unchanged in their pups. Several studies have associated these hematological disorders with oxidative stress. In fact, GA(3) treatment revealed in erythrocytes a significant increase in malondialdehyde levels and a decrease in antioxidant enzyme activities such as superoxide dismutase, catalase, and glutathione peroxidase. Moreover, a significant decline was observed in acetylcholinesterase activity, glutathione, nonprotein thiols, and vitamin C levels. PMID- 22064683 TI - Heterogeneity mapping of protein expression in tumors using quantitative immunofluorescence. AB - Morphologic heterogeneity within an individual tumor is well-recognized by histopathologists in surgical practice. While this often takes the form of areas of distinct differentiation into recognized histological subtypes, or different pathological grade, often there are more subtle differences in phenotype which defy accurate classification (Figure 1). Ultimately, since morphology is dictated by the underlying molecular phenotype, areas with visible differences are likely to be accompanied by differences in the expression of proteins which orchestrate cellular function and behavior, and therefore, appearance. The significance of visible and invisible (molecular) heterogeneity for prognosis is unknown, but recent evidence suggests that, at least at the genetic level, heterogeneity exists in the primary tumor(1,2), and some of these sub-clones give rise to metastatic (and therefore lethal) disease. Moreover, some proteins are measured as biomarkers because they are the targets of therapy (for instance ER and HER2 for tamoxifen and trastuzumab (Herceptin), respectively). If these proteins show variable expression within a tumor then therapeutic responses may also be variable. The widely used histopathologic scoring schemes for immunohistochemistry either ignore, or numerically homogenize the quantification of protein expression. Similarly, in destructive techniques, where the tumor samples are homogenized (such as gene expression profiling), quantitative information can be elucidated, but spatial information is lost. Genetic heterogeneity mapping approaches in pancreatic cancer have relied either on generation of a single cell suspension(3), or on macrodissection(4). A recent study has used quantum dots in order to map morphologic and molecular heterogeneity in prostate cancer tissue(5), providing proof of principle that morphology and molecular mapping is feasible, but falling short of quantifying the heterogeneity. Since immunohistochemistry is, at best, only semi-quantitative and subject to intra- and inter-observer bias, more sensitive and quantitative methodologies are required in order to accurately map and quantify tissue heterogeneity in situ. We have developed and applied an experimental and statistical methodology in order to systematically quantify the heterogeneity of protein expression in whole tissue sections of tumors, based on the Automated QUantitative Analysis (AQUA) system(6). Tissue sections are labeled with specific antibodies directed against cytokeratins and targets of interest, coupled to fluorophore-labeled secondary antibodies. Slides are imaged using a whole-slide fluorescence scanner. Images are subdivided into hundreds to thousands of tiles, and each tile is then assigned an AQUA score which is a measure of protein concentration within the epithelial (tumor) component of the tissue. Heatmaps are generated to represent tissue expression of the proteins and a heterogeneity score assigned, using a statistical measure of heterogeneity originally used in ecology, based on the Simpson's biodiversity index(7). To date there have been no attempts to systematically map and quantify this variability in tandem with protein expression, in histological preparations. Here, we illustrate the first use of the method applied to ER and HER2 biomarker expression in ovarian cancer. Using this method paves the way for analyzing heterogeneity as an independent variable in studies of biomarker expression in translational studies, in order to establish the significance of heterogeneity in prognosis and prediction of responses to therapy. PMID- 22064684 TI - tert-Butyl-aminium 2-carb-oxy-4,5-dichloro-benzoate. AB - In the structure of the title anhydrous salt, C(4)H(12)N(+).C(8)H(3)Cl(2)O(4) ( ), the 4,5-dichloro-phthalate monoanions have the common 'planar' conformation with the carboxyl groups close to coplanar with the benzene ring and with a short intra-molecular carb-oxy-lic acid O-H?O hydrogen bond. In the crystal, a two dimensional sheet structure is formed through aminium N-H?O(carbox-yl) hydrogen bonding associations. PMID- 22064685 TI - Imaging odor-evoked activities in the mouse olfactory bulb using optical reflectance and autofluorescence signals. AB - In the brain, sensory stimulation activates distributed populations of neurons among functional modules which participate to the coding of the stimulus. Functional optical imaging techniques are advantageous to visualize the activation of these modules in sensory cortices with high spatial resolution. In this context, endogenous optical signals that arise from molecular mechanisms linked to neuroenergetics are valuable sources of contrast to record spatial maps of sensory stimuli over wide fields in the rodent brain. Here, we present two techniques based on changes of endogenous optical properties of the brain tissue during activation. First the intrinsic optical signals (IOS) are produced by a local alteration in red light reflectance due to: (i) absorption by changes in blood oxygenation level and blood volume (ii) photon scattering. The use of in vivo IOS to record spatial maps started in the mid 1980's with the observation of optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex(1). IOS imaging of the surface of the rodent main olfactory bulb (OB) in response to odorants was later demonstrated by Larry Katz's group(2). The second approach relies on flavoprotein autofluorescence signals (FAS) due to changes in the redox state of these mitochondrial metabolic intermediates. More precisely, the technique is based on the green fluorescence due to oxidized state of flavoproteins when the tissue is excited with blue light. Although such signals were probably among the first fluorescent molecules recorded for the study of brain activity by the pioneer studies of Britton Chances and colleagues(3), it was not until recently that they have been used for mapping of brain activation in vivo. FAS imaging was first applied to the somatosensory cortex in rodents in response to hindpaw stimulation by Katsuei Shibuki's group(4). The olfactory system is of central importance for the survival of the vast majority of living species because it allows efficient detection and identification of chemical substances in the environment (food, predators). The OB is the first relay of olfactory information processing in the brain. It receives afferent projections from the olfactory primary sensory neurons that detect volatile odorant molecules. Each sensory neuron expresses only one type of odorant receptor and neurons carrying the same type of receptor send their nerve processes to the same well-defined microregions of ~100MUm(3) constituted of discrete neuropil, the olfactory glomerulus (Fig. 1). In the last decade, IOS imaging has fostered the functional exploration of the OB(5, 6, 7) which has become one of the most studied sensory structures. The mapping of OB activity with FAS imaging has not been performed yet. Here, we show the successive steps of an efficient protocol for IOS and FAS imaging to map odor-evoked activities in the mouse OB. PMID- 22064687 TI - The potential for central monitoring techniques to replace on-site monitoring: findings from an international multi-centre clinical trial. AB - BACKGROUND: Compliance with Good Clinical Practice (GCP) guidelines should ensure the safety of trial participants and the reliability of trial results. Over the last decade, increasing emphasis has been placed on the role of costly on-site monitoring and source data verification as processes to demonstrate that GCP is being followed, despite a lack of empirical evidence that these are effective. PURPOSE: To assess whether findings from on-site monitoring of a recent international multi-centre clinical trial could have been identified using central data review and other centralised monitoring techniques. METHODS: Findings documented in a sample of site monitoring reports, and Programme Management Board Executive (PMBe) reports, from the Microbicides Development Programme (MDP) 301 trial - a randomised placebo-controlled trial of a microbicide gel to prevent vaginally acquired HIV infection conducted in four countries in East and Southern Africa - were extracted and individually assessed to determine whether they could have been detected in the trial database or through other central means. RESULTS: Four site visit reports contained 268 monitoring findings from a review of 104 participant files covering 324 study visits. Of the 268 findings, 76 (28.4%) were also identified in the study database. Central checks, had these been in place (such as central receipt and review of back-translated documents, enrolment and testing logs, informed consent, and more complex database queries), could have identified a further 179 (66.8%); 13 (4.9%) other findings (all minor) could have been identified through a review of the participant folder at site. The four PMBe reports reviewed included six major and three critical findings from a review of over 1000 participant files: only two of these (both major) were assessed as unlikely to be identified using central monitoring techniques. LIMITATIONS: The study data used were not collected with this retrospective review in mind. It suggests that prospective work is needed to compare monitoring practices in real time. CONCLUSIONS: While there may be some categories of findings that it is not possible to identify centrally, the very large majority of findings reviewed in this analysis could be identified using central monitoring strategies. These data suggest that with better central and targeted on-site monitoring, it should be possible to identify and address most protocol and procedural compliance issues without performing intensive and costly routine on-site data monitoring. PMID- 22064688 TI - Single read and paired end mRNA-Seq Illumina libraries from 10 nanograms total RNA. AB - Whole transcriptome sequencing by mRNA-Seq is now used extensively to perform global gene expression, mutation, allele-specific expression and other genome wide analyses. mRNA-Seq even opens the gate for gene expression analysis of non sequenced genomes. mRNA-Seq offers high sensitivity, a large dynamic range and allows measurement of transcript copy numbers in a sample. Illumina's genome analyzer performs sequencing of a large number (> 10(7)) of relatively short sequence reads (< 150 bp).The "paired end" approach, wherein a single long read is sequenced at both its ends, allows for tracking alternate splice junctions, insertions and deletions, and is useful for de novo transcriptome assembly. One of the major challenges faced by researchers is a limited amount of starting material. For example, in experiments where cells are harvested by laser micro dissection, available starting total RNA may measure in nanograms. Preparation of mRNA-Seq libraries from such samples have been described(1, 2) but involves significant PCR amplification that may introduce bias. Other RNA-Seq library construction procedures with minimal PCR amplification have been published(3, 4) but require microgram amounts of starting total RNA. Here we describe a protocol for the Illumina Genome Analyzer II platform for mRNA-Seq sequencing for library preparation that avoids significant PCR amplification and requires only 10 nanograms of total RNA. While this protocol has been described previously and validated for single-end sequencing(5), where it was shown to produce directional libraries without introducing significant amplification bias, here we validate it further for use as a paired end protocol. We selectively amplify polyadenylated messenger RNAs from starting total RNA using the T7 based Eberwine linear amplification method, coined "T7LA" (T7 linear amplification). The amplified poly A mRNAs are fragmented, reverse transcribed and adapter ligated to produce the final sequencing library. For both single read and paired end runs, sequences are mapped to the human transcriptome(6) and normalized so that data from multiple runs can be compared. We report the gene expression measurement in units of transcripts per million (TPM), which is a superior measure to RPKM when comparing samples(7). PMID- 22064689 TI - Bis(1,10-phenanthroline-kappaN,N')(sulfato-O)copper(II) ethane-1,2-diol monosolvate. AB - In the title compound, [Cu(SO(4))(C(12)H(8)N(2))(2)].C(2)H(6)O(2), the Cu(II) ion is five-coordinated in a distorted square-pyramidal manner by four N atoms from two chelating 1,10-phenanthroline (phen) ligands and one O atom from a monodentate sulfate anion. The four N atoms comprise a square and the one O atom the apex of a square pyramid. The two chelating N(2)C(2) groups are oriented at 71.1 (2) degrees . In the crystal, the components are connected by inter molecular O-H?O hydrogen bonding. The presence of pseudosymmetry in the structure suggests the higher symmetry space group C2/c, but attempts to refine the structure in this space group resulted in an unsatisfactory model. PMID- 22064686 TI - Factors influencing enrollment of African Americans in the Look AHEAD trial. AB - BACKGROUND: Many factors have been identified that influence the recruitment of African Americans into clinical trials; however, the influence of eligibility criteria may not be widely appreciated. We used the experience from the Look AHEAD (Action for Health in Diabetes) trial screening process to examine the differential impact eligibility criteria had on the enrollment of African Americans compared to other volunteers. METHODS: Look AHEAD is a large randomized clinical trial to examine whether assignment to an intensive lifestyle intervention designed to produce and maintain weight loss reduces the long-term risk of major cardiovascular events in adults with type 2 diabetes. Differences in the screening, eligibility, and enrollment rates between African Americans and members of other racial/ethnic groups were examined to identify possible reasons. RESULTS: Look AHEAD screened 28,735 individuals for enrollment, including 6226 (21.7%) who were self-identified African Americans. Of these volunteers, 12.9% of the African Americans compared to 19.3% of all other screenees ultimately enrolled (p < 0.001). African Americans no more often than others were lost to follow-up or refused to attend clinic visits to establish eligibility. Furthermore, the enrollment rates of individuals with histories of cardiovascular disease and diabetes therapy did not markedly differ between the ethnic groups. Higher prevalence of adverse levels of blood pressure, heart rate, HbA1c, and serum creatinine among African American screenees accounted for the greater proportions excluded (all p < 0.001). CONCLUSIONS: Compared to non-African Americans, African American were more often ineligible for the Look AHEAD trial due to comorbid conditions. Monitoring trial eligibility criteria for differential impact, and modifying them when appropriate, may ensure greater enrollment yields. PMID- 22064690 TI - 2-Bromo-N-(4-chloro-phen-yl)-2-methyl-propanamide. AB - In the title mol-ecule, C(10)H(11)BrClNO, there is a twist between the mean plane of the amide group and the benzene ring [C(=O)-N-C-C torsion angle = -27.1 (3) degrees ]. In the crystal, inter-molecular N-H?O and weak C-H?O hydrogen bonds link the mol-ecules into chains along [010]. PMID- 22064691 TI - Participant modelling: an effective treatment strategy for stammering. AB - Six cases of stammering, free from gross organic and psychological abnormality were taken up for treatment by participant modelling. All the cases showed substantial improvement with this treatment model ty. PMID- 22064692 TI - (E)-1-{4-[Bis(4-meth-oxy-phen-yl)meth-yl]piperazin-1-yl}-3-(4-methyl-phen-yl)prop 2-en-1-one. AB - In the title mol-ecule, C(29)H(32)N(2)O(3), the piperazine ring has a chair conformation. The amide N atom is almost planar (bond angle sum = 359.5 degrees ), whereas the other N atom is clearly pyramidal (bond angle sum = 330.4 degrees ). The dihedral angle between the meth-oxy-benzene rings is 81.29 (16) degrees . In the crystal, mol-ecules are linked by C-H?O hydrogen bonds. PMID- 22064693 TI - N-(2-Amino-4,6-dihydroxypyrimidin-5-yl)acetamide dihydrate. AB - The title compound, C(6)H(8)N(4)O(3).2H(2)O, which crystallized as a dihydrate, has two almost planar segments viz. the pyrimidine ring and the C-N-C(=O)-C group [maxmum deviations of 0.020 (2) and 0.014 (2) A, respectively], with a dihedral angle of 87.45 degrees . In the crystal, the components are linked by O-H?O and N H?O hydrogen bonds. PMID- 22064694 TI - 4-(4-Chloro-phen-yl)-8-methyl-2-oxo-1,2,3,4,4a,5,6,7-octa-hydro-quinoline-3 carbonitrile. AB - The six-membered N-heterocyclic ring of title compound, C(17)H(17)ClN(2)O, is fused with a methyl-substituted cyclo-hexene ring. The nitro-gen-bearing ring has an envelope conformation with the benzene ring-bearing C atom lying 0.432 (6) A out of the plane defined by the other five atoms (r.m.s. deviation 0.011 A); its benzene substituent is aligned at 84.7 (1) degrees to the latter plane. The cyclo-hexene ring adopts a half-chair conformation. In the crystal, two mol ecules are linked about a center of inversion by pairs of N-H?O hydrogen bonds, generating dimers. An ethyl-ene portion is disordered over two orientations in a 1:1 ratio. The crystal studied was a non-merohedral twin with a 15.3 (1)% minor component. PMID- 22064695 TI - Isolation and expansion of human glioblastoma multiforme tumor cells using the neurosphere assay. AB - Stem-like cells have been isolated in tumors such as breast, lung, colon, prostate and brain. A critical issue in all these tumors, especially in glioblastoma mutliforme (GBM), is to identify and isolate tumor initiating cell population(s) to investigate their role in tumor formation, progression, and recurrence. Understanding tumor initiating cell populations will provide clues to finding effective therapeutic approaches for these tumors. The neurosphere assay (NSA) due to its simplicity and reproducibility has been used as the method of choice for isolation and propagation of many of this tumor cells. This protocol demonstrates the neurosphere culture method to isolate and expand stem-like cells in surgically resected human GBM tumor tissue. The procedures include an initial chemical digestion and mechanical dissociation of tumor tissue, and subsequently plating the resulting single cell suspension in NSA culture. After 7-10 days, primary neurospheres of 150-200 MUm in diameter can be observed and are ready for further passaging and expansion. PMID- 22064696 TI - Coronary artery disease is detectable by multi-slice computed tomography in most asymptomatic type 2 diabetic patients at high cardiovascular risk. AB - OBJECTIVE: Non-invasive testing often does not identify coronary artery disease (CAD) in diabetic subjects. This study was designed in order to examine the prevalence of CAD in a cohort of asymptomatic type 2 diabetic patients at high cardiovascular risk and negative nuclear imaging, using multi-slice computed tomography (MSCT) angiography. METHODS: In total, 770 type 2 diabetic patients were screened from January 2008 through July 2010. Of these, 132 Caucasians with diabetic nephropathy and asymptomatic for angina were eligible for a cross sectional study. Patients underwent MSCT after ischaemia was excluded by myocardial Single Photon Emission Computed Tomography (SPECT) at rest and after dynamic exercise. When obstructive plaques were found (>= 50% lumen narrowing), patients were sent to conventional coronary angiography (CCA). RESULTS: Six subjects were not included in the analysis because of motion artefacts. MSCT was positive for CAD in 114 patients (90%). Within patients with positive MSCT, 60 (48% of all) showed one or more obstructive plaques. CCA confirmed significant stenosis (>= 50%) in 48 of these 60 patients (80%). Some 21 (35%) showed stenosis >= 75% and were submitted to the revascularisation procedure. CONCLUSION: MSCT seems to better identify CAD than myocardial SPECT in asymptomatic patients with type 2 diabetes and diabetic nephropathy. PMID- 22064697 TI - Vascular endothelial growth factor polymorphisms are involved in the late vascular complications in Type II diabetic patients. AB - AIM: To determine the potential genotype differences in the vascular endothelial growth factor (VEGF) gene in diabetic patients, which might explain the difference in terms of the development of clinical vascular complications: great vessels atherosclerosis vs. retinopathy. METHODS: Genotyping of the VEFG gene insertion/deletion -2549, the C-2578A and the G+405C polymorphisms was done in 40 diabetic patients (26 with peripheral artery disease (PAD) and 14 with diabetic retinopathy (DR)). RESULTS: There was a significant increase in the frequency of the VEGF -2549 DD genotype in PAD patients compared with the DR group (34.6 vs. 0; p = 0.016), as well as in the distribution of the VEGF -2549 ID genotype in DR compared with PAD patients (85.7 vs. 38.4; p = 0.005). There was a significant increase in the frequency of the VEGF -2578 CC genotype in the PAD group compared with DR (34.6 vs. 0; p = 0.016), as well as in the VEGF -2578 CA genotype in DR patients compared with PAD (85.7 vs. 34.6; p = 0.002). The VEGF +405 genotype was not associated with diabetic vascular complications. CONCLUSION: This study provides preliminary evidence that VEGF polymorphisms are associated with a differential presentation of diabetic vascular complications. PMID- 22064698 TI - Shh signaling guides spatial pathfinding of raphespinal tract axons by multidirectional repulsion. AB - Relatively little is known about the molecular mechanisms underlying spatial pathfinding in the descending serotonergic raphespinal tract (RST) in the developing spinal cord, one of the most important nerve pathways for pain, sensory and motor functions. We provide evidence that ventral floor plate secreted Sonic hedgehog (Shh) is responsible for the establishment of decreasing gradients in both the anterior-to-posterior (A-P) and the medial-to-lateral (M-L) directions in the ventral spinal cord during serotonergic RST axon projection. Downstream components of the Shh pathway, Patched 1 (Ptch1) and Smoothened (Smo), were expressed in the serotonergic caudal raphe nuclei and enriched in the descending serotonergic RST axons. Diffusible Shh repulsion of serotonergic RST axons was shown to be mediated by Shh-Ptch1 interactions and derepression of Smo. Using a co-culture assay, we showed that A-P graded repulsion mediated by Shh signaling pushed the serotonergic axons caudally through the ventral spinal cord and M-L graded repulsion mediated by Shh signaling simultaneously restricted the serotonergic axons to the ventral and ventral-lateral funiculus. Prominent pathfinding errors of serotonergic RST axons were observed in various Shh, Ptch1 and Smo mutants. We conclude that Shh signaling-mediated multidirectional repulsion is required to push descending serotonergic RST axons in the A-P direction, and to restrict these axons to the ventral and ventral-lateral funiculus in the M-L direction. This is the first demonstration that Shh signaling-mediated multidirectional repulsion of serotonergic RST axons maintains spatial axon pathfinding in the developing spinal cord. PMID- 22064699 TI - Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature. AB - Cardiomyocytes derived from pluripotent stem cells can be applied in drug testing, disease modeling and cell-based therapy. However, without procardiogenic growth factors, the efficiency of cardiomyogenesis from pluripotent stem cells is usually low and the resulting cardiomyocyte population is heterogeneous. Here, we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes (VMs), and consistent with other reports of iPSCs derived from various somatic cell types, VM-derived iPSCs (ViPSCs) exhibit a markedly higher propensity to spontaneously differentiate into beating cardiomyocytes as compared to genetically matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts. Strikingly, the majority of ViPSC derived cardiomyocytes display a ventricular phenotype. The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation. In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs, we performed global gene expression and DNA methylation analysis, which revealed a distinct epigenetic signature that may be involved in specifying the VM fate in pluripotent stem cells. PMID- 22064700 TI - Direct reprogramming of Sertoli cells into multipotent neural stem cells by defined factors. AB - Multipotent neural stem/progenitor cells hold great promise for cell therapy. The reprogramming of fibroblasts to induced pluripotent stem cells as well as mature neurons suggests a possibility to convert a terminally differentiated somatic cell into a multipotent state without first establishing pluripotency. Here, we demonstrate that Sertoli cells derived from mesoderm can be directly converted into a multipotent state that possesses neural stem/progenitor cell properties. The induced neural stem/progenitor cells (iNSCs) express multiple NSC-specific markers, exhibit a global gene-expression profile similar to normal NSCs, and are capable of self-renewal and differentiating into glia and electrophysiologically functional neurons. iNSC-derived neurons stain positive for tyrosine hydroxylase (TH), gamma-aminobutyric acid, and choline acetyltransferase. In addition, iNSCs can survive and generate synapses following transplantation into the dentate gyrus. Generation of iNSCs may have important implications for disease modeling and regenerative medicine. PMID- 22064701 TI - The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. AB - Metabolism is vital to every aspect of cell function, yet the metabolome of induced pluripotent stem cells (iPSCs) remains largely unexplored. Here we report, using an untargeted metabolomics approach, that human iPSCs share a pluripotent metabolomic signature with embryonic stem cells (ESCs) that is distinct from their parental cells, and that is characterized by changes in metabolites involved in cellular respiration. Examination of cellular bioenergetics corroborated with our metabolomic analysis, and demonstrated that somatic cells convert from an oxidative state to a glycolytic state in pluripotency. Interestingly, the bioenergetics of various somatic cells correlated with their reprogramming efficiencies. We further identified metabolites that differ between iPSCs and ESCs, which revealed novel metabolic pathways that play a critical role in regulating somatic cell reprogramming. Our findings are the first to globally analyze the metabolome of iPSCs, and provide mechanistic insight into a new layer of regulation involved in inducing pluripotency, and in evaluating iPSC and ESC equivalence. PMID- 22064703 TI - S phase-dependent interaction with DNMT1 dictates the role of UHRF1 but not UHRF2 in DNA methylation maintenance. AB - Recent studies demonstrate that UHRF1 is required for DNA methylation maintenance by targeting DNMT1 to DNA replication foci, presumably through its unique hemi methylated DNA-binding activity and interaction with DNMT1. UHRF2, another member of the UHRF family proteins, is highly similar to UHRF1 in both sequence and structure, raising questions about its role in DNA methylation. In this study, we demonstrate that, like UHRF1, UHRF2 also binds preferentially to methylated histone H3 lysine 9 (H3K9) through its conserved tudor domain and hemi-methylated DNA through the SET and Ring associated domain. Like UHRF1, UHRF2 is enriched in pericentric heterochromatin. The heterochromatin localization depends to large extent on its methylated H3K9-binding activity and to less extent on its methylated DNA-binding activity. Coimmunoprecipitation experiments demonstrate that both UHRF1 and UHRF2 interact with DNMT1, DNMT3a, DNMT3b and G9a. Despite all these conserved functions, we find that UHRF2 is not able to rescue the DNA methylation defect in Uhrf1 null mouse embryonic stem cells. This can be attributed to the inability for UHRF2 to recruit DNMT1 to replication foci during S phase of the cell cycle. Indeed, we find that while UHRF1 interacts with DNMT1 in an S phase-dependent manner in cells, UHRF2 does not. Thus, our study demonstrates that UHRF2 and UHRF1 are not functionally redundant in DNA methylation maintenance and reveals the cell-cycle-dependent interaction between UHRF1 and DNMT1 as a key regulatory mechanism targeting DNMT1 for DNA methylation. PMID- 22064704 TI - An atypical component of RNA-directed DNA methylation machinery has both DNA methylation-dependent and -independent roles in locus-specific transcriptional gene silencing. AB - RNA-directed DNA methylation (RdDM) is an important de novo DNA methylation pathway in plants. RdDM mediates the transcriptional silencing of many endogenous genomic loci, most of which are transposon related. A forward genetics screen identified DTF1 (DNA-binding transcription factor 1) as a new component for RdDM in Arabidopsis. Loss-of-function mutations in DTF1 release the transcriptional silencing of RdDM target loci and reduce the accumulation of 24-nt small interfering RNAs (siRNAs) from some of the targets. Interestingly, in the dtf1 mutant plants, the release of transcriptional gene silencing at solo-LTR is accompanied by decreased siRNA accumulation but not by reduced DNA methylation. These results suggest that DTF1 is an atypical component of RdDM and has both DNA methylation-dependent and -independent roles in transcriptional gene silencing. We suggest that besides DNA methylation, siRNAs may cause some other uncharacterized epigenetic modifications that lead to transcriptional gene silencing. PMID- 22064705 TI - 4-(1,3-Benzothia-zol-2-yl)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one. AB - The central five-membered ring of the title compound, C(18)H(15)N(3)OS, is almost planar (r.m.s. deviation = 0.028 A) and the benzothia-zole fused-ring system is close to coplanar with this ring [dihedral angle = 6.1 (1) degrees ]. The phenyl substituent is twisted by 62.5 (1) degrees . PMID- 22064706 TI - Macrophage migration inhibitory factor deficiency protects pancreatic islets from palmitic acid-induced apoptosis. AB - As a result of chronic exposure to high levels of free fatty acids, glucose and inflammatory mediators beta-cell apoptosis occurs at the end stage of obesity associated type 2 diabetes (T2D). One potentially deleterious molecule for beta cell function associated with T2D and obesity in humans is macrophage migration inhibitory factor (MIF). Therefore, the aim of this study was to explore MIF expression in vivo during development of obesity and insulin resistance in high fat diet (HFD)-fed C57BL/6 mice and whether MIF inhibition could affect beta-cell apoptosis and dysfunction induced by palmitic acid (PA) in vitro. Indeed, increase in systemic and locally produced MIF correlated well with the weight gain, triglyceride upregulation, glucose intolerance and insulin resistance, which developed in HFD-fed mice. In in vitro settings PA dose-dependently induced MIF secretion before apoptosis development in islets. Further, mif gene deletion, mRNA silencing or protein inhibition rescued beta-cells from PA-induced apoptosis as measured by MTT assay and histone-DNA enzyme linked immuno sorbent assay. Protection from induced apoptosis was mediated by altered activation of caspase pathway and correlated with changes in the level of Bcl-2 family members. Further, MIF inhibition conveyed a significant resistance to PA-induced downregulation of insulin and PDX-1 expression and ATP content. However, beta cell function was not entirely preserved in the absence of MIF judging by low glucose oxidation and depolarized mitochondrial membrane. In conclusion, the observed considerable preservation of beta-cells from nutrient-induced apoptosis might implicate MIF as a potential therapeutic target in the later stage of obesity-associated T2D. PMID- 22064708 TI - Histone deacetylase inhibitors in the generation of the anti-tumour immune response. AB - Acetylation of lysine residues acts to modify the function of a wide range of proteins. In histones, it affects chromatin structure, which can impact gene transcription, whereas acetylation of transcription factors and heat-shock proteins affect their activity. Deacetylase inhibitors block the dynamic turnover of acetylation resulting in hyperacetylation of target proteins. This can affect a wide range of cellular functions, and in a wide range of tumour cell types promote cytostatic and cytotoxic effects, but has little effect on normal cells. The inhibitors are being used clinically as anti-cancer agents. Although direct effects of the histone deacetylase (HDAC) inhibitors on cancers are beginning to be elucidated, the prospect of concurrent stimulation of the immune response raises hopes for immune attack of the tumour as part of the initial anti-cancer therapy and long-term immune-surveillance of residual or recurrent tumour. This review will examine the evidence for the generation of anti-tumour immunity after treatment of cancers with HDAC inhibitors. PMID- 22064707 TI - Insights into inflammatory bowel disease using Toxoplasma gondii as an infectious trigger. AB - Oral infection of certain inbred mouse strains with the protozoan Toxoplasma gondii triggers inflammatory pathology resembling lesions seen during human inflammatory bowel disease, in particular Crohn's disease (CD). Damage triggered by the parasite is largely localized to the distal portion of the small intestine, and as such is one of only a few models for ileal inflammation. This is important because ileal involvement is a characteristic of CD in over two thirds of patients. The disease induced by Toxoplasma is mediated by Th1 cells and the cytokines tumor necrosis factor-alpha and interferon-gamma. Inflammation is dependent upon IL-23, also identified by genome-wide association studies as a risk factor in CD. Development of lesions is concomitant with emergence of E. coli that display enhanced adhesion to the intestinal epithelium and subepithelial translocation. Furthermore, depletion of gut flora renders mice resistant to Toxoplasma-triggered ileitis. Recent findings suggest complex CCR2 dependent interactions between lamina propria T cells and intraepithelial lymphocytes in fueling proinflammatory pathology in the intestine. The advantage of the Toxoplasma model is that disease develops rapidly (within 7-10 days of infection) and can be induced in immunodeficient mice by adoptive transfer of mucosal T cells from infected donors. We propose that Toxoplasma acts as a trigger setting into motion a series of events culminating in loss of tolerance in the intestine and emergence of pathogenic T cell effectors. The Toxoplasma trigger model is providing new leaps in our understanding of immunity in the intestine. PMID- 22064710 TI - 1,8-Bis(4-meth-oxy-3-nitro-phen-yl)naphthalene. AB - Mol-ecules of the title compound, C(24)H(18)N(2)O(6), are located on a twofold rotation axis passing through through the central C-C bond of the naphthalene ring system. The mol-ecular conformation is characterized by a roughly coplanar arrangement of the two substituted phenyl rings [dihedral angle 18.53 (5) degrees ]. These two aryl rings are each twisted by 65.40 (5) degrees from the plane of the naphthyl unit. PMID- 22064711 TI - Two strikingly different signaling pathways are induced by meningococcal type IV pili on endothelial and epithelial cells. AB - Following adhesion on brain microvasculature, Neisseria meningitidis is able to cross the blood-brain barrier (BBB) by recruiting the polarity complex and the cell junction proteins, thus allowing the opening of the paracellular route. This feature is the consequence of the activation by the type IV pili of the beta2 adrenergic receptor/beta-arrestin signaling pathway. Here, we have extended this observation to primary peripheral endothelial cells, and we report that the interaction of N. meningitidis with the epithelium is strikingly different. The recruitment of the junctional components by N. meningitidis is indeed restricted to endothelial cell lines, and no alteration of the cell-cell junctions can be seen in epithelial monolayers following meningococcal type IV pilus-mediated colonization. Consistently, the beta2-adrenergic receptor/beta-arrestin pathway was not hijacked by bacteria adhering on epithelial cells. In addition, we showed that the consequences of the bacterial signaling on epithelial cells is different from that of endothelial cells, since N. meningitidis-induced signaling which protects the microcolonies from shear stress on endothelial cells is unable to do so on epithelial cells. Finally, we report that the minor pilin PilV, which has been shown to be essential for endothelial cell response, is not a required bacterial determinant to induce an epithelial cell response. These data demonstrate that even though pilus-mediated signaling induces an apparently similar cortical plaque, in epithelial and endothelial cell lineages, the signaling pathways are strikingly different in both models. PMID- 22064712 TI - Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein. AB - Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density. PMID- 22064713 TI - Macrophages are critical for cross-protective immunity conferred by Babesia microti against Babesia rodhaini infection in mice. AB - Although primary infection of mice with Babesia microti has been shown to protect mice against subsequent lethal infection by Babesia rodhaini, the mechanism behind the cross-protection is unknown. To unravel this mechanism, we investigated the influence of primary infection of mice with nonlethal B. microti using different time courses on the outcome of subsequent lethal B. rodhaini infection. Simultaneous infections of mice with these parasites resulted in rapid increases in parasitemia, with 100% mortality in BALB/c mice, as observed with control mice infected with B. rodhaini alone. In contrast, mice with acute, resolving, and chronic-phase B. microti infections were completely protected against B. rodhaini, resulting in low parasitemia and no mortalities. Mice immunized with dead B. microti were not protected from B. rodhaini infection, although high antibody responses were induced. Interestingly, the protected mice had significantly decreased levels of antibody response, cytokines (including gamma interferon [IFN-gamma], interleukin-2 [IL-2], IL-8, IL-10, and IL-12), and nitric oxide levels after infection with B. rodhaini. SCID mice and IFN-gamma deficient mice with chronic B. microti infections demonstrated protective responses comparable to those of immunocompetent mice. Likewise, in vivo NK cell depletion did not significantly impair the protective responses. Conversely, macrophage depletion resulted in increased susceptibility to B. rodhaini infection associated with changes in their antibody and cytokines profiles, indicating that macrophages contribute to the protection against this challenge infection. We conclude that future development of vaccines against Babesia should include a strategy that enhances the appropriate activation of macrophages. PMID- 22064714 TI - A protective epitope in type III effector YopE is a major CD8 T cell antigen during primary infection with Yersinia pseudotuberculosis. AB - Virulence in human-pathogenic Yersinia species is associated with a plasmid encoded type III secretion system that translocates a set of Yop effector proteins into host cells. One effector, YopE, functions as a Rho GTPase activating protein (GAP). In addition to acting as a virulence factor, YopE can function as a protective antigen. C57BL/6 mice infected with attenuated Yersinia pestis generate a dominant H2-Kb-restricted CD8 T cell response to an epitope in the N-terminal domain of YopE (YopE69-77), and intranasal vaccination with the YopE69-77 peptide and the mucosal adjuvant cholera toxin (CT) elicits CD8 T cells that are protective against lethal pulmonary challenge with Y. pestis. Because YopE69-77 is conserved in many Yersinia strains, we sought to determine if YopE is a protective antigen for Yersinia pseudotuberculosis and if primary infection with this enteric pathogen elicits a CD8 T cell response to this epitope. Intranasal immunization with the YopE69-77 peptide and CT elicited a CD8 T cell response that was protective against lethal intragastric Y. pseudotuberculosis challenge. The YopE69-77 epitope was a major antigen (~30% of splenic CD8 T cells were specific for this peptide at the peak of the response) during primary infection with Y. pseudotuberculosis, as shown by flow cytometry tetramer staining. Results of infections with Y. pseudotuberculosis expressing catalytically inactive YopE demonstrated that GAP activity is dispensable for a CD8 T cell response to YopE69-77. Determining the features of YopE that are important for this response will lead to a better understanding of how protective CD8 T cell immunity is generated against Yersinia and other pathogens with type III secretion systems. PMID- 22064715 TI - Pathophysiology of the rhesus macaque model for inhalational brucellosis. AB - The objective of this study was to characterize the rhesus macaque (RM) as a model for inhalational brucellosis in support of the U.S. Food and Drug Administration's (FDA) Animal Rule. The pathophysiology of chronic Brucella melitensis aerosol infection was monitored in two phases that each occurred over an 8-week time period; dose escalation (8 RMs; targeted doses of 5.0E+03, 5.0E+04, or 5.0E+05 CFU/animal or the unchallenged control) and natural history (12 RMs; targeted dose of 2.50E+05 CFU/animal or the unchallenged control). RMs given an aerosol challenge with B. melitensis developed undulating fevers (6/6 phase I; 8/9 phase II), positive enriched blood cultures (5/10; phase II), and bacterial burdens in tissues starting 14 to 21 days postchallenge (6/6 phase I; 10/10 phase II). In addition, 80% (8/10; phase II) of infected RMs seroconverted 14 to 21 days postchallenge. RMs developed elevations in certain liver enzymes and had an increased inflammatory response by 3 weeks postchallenge as shown by increases in C-reactive protein (6/8) and neopterin (4/8), which correlated with the onset of a fever. As early as 14 days postchallenge, positive liver biopsy specimens were detected (2/8), and ultrasound imaging showed the development of splenomegaly. Finally, histopathologic examination found lesions attributed to Brucella infection in the liver, kidney, lung, and/or spleen of all animals. The disease progression observed with the RMs in this study is analogous to human brucellosis pathophysiology. Thus, the results from this study support the use of the RM as an animal model for inhalational brucellosis to evaluate the efficacy of novel vaccines and therapeutics against B. melitensis. PMID- 22064716 TI - Repeated exposure to Aspergillus fumigatus conidia results in CD4+ T cell dependent and -independent pulmonary arterial remodeling in a mixed Th1/Th2/Th17 microenvironment that requires interleukin-4 (IL-4) and IL-10. AB - Pulmonary arterial remodeling is a pathological process seen in a number of clinical disease states, driven by inflammatory cells and mediators in the remodeled artery microenvironment. In murine models, Th2 cell-mediated immune responses to inhaled antigens, such as purified Aspergillus allergen, have been reported to induce remodeling of pulmonary arteries. We have previously shown that repeated intranasal exposure of healthy C57BL/6 mice to viable, resting Aspergillus fumigatus conidia leads to the development of chronic pulmonary inflammation and the coevolution of Th1, Th2, and Th17 responses in the lungs. Our objective was to determine whether repeated intranasal exposure to Aspergillus conidia would induce pulmonary arterial remodeling in this mixed Th inflammatory microenvironment. Using weekly intranasal conidial challenges, mice developed robust pulmonary arterial remodeling after eight exposures (but not after two or four). The process was partially mediated by CD4+ T cells and by interleukin-4 (IL-4) production, did not require eosinophils, and was independent of gamma interferon (IFN-gamma) and IL-17. Furthermore, remodeling could occur even in the presence of strong Th1 and Th17 responses. Rather than serving an anti-inflammatory function, IL-10 was required for the development of the Th2 response to A. fumigatus conidia. However, in contrast to previous studies of pulmonary arterial remodeling driven by the A. fumigatus allergen, viable conidia also stimulated pulmonary arterial remodeling in the absence of CD4+ T cells. Remodeling was completely abrogated in IL-10-/- mice, suggesting that a second, CD4+ T cell-independent, IL-10-dependent pathway was also driving pulmonary arterial remodeling in response to repeated conidial exposure. PMID- 22064717 TI - Defining the roles of human carcinoembryonic antigen-related cellular adhesion molecules during neutrophil responses to Neisseria gonorrhoeae. AB - Symptomatic infection of humans with Neisseria gonorrhoeae is characterized by a neutrophil-rich cervical or urethral exudate, suggesting that neutrophils are important both for the clearance of these bacteria and for the pathogenesis of gonorrhea. Neisseria interacts with neutrophils through ligation of human carcinoembryonic antigen related-cellular adhesion molecules (CEACAMs) by their surface-expressed Opa proteins, resulting in bacterial binding, engulfment, and neutrophil activation. Multiple CEACAMs are expressed by human neutrophils, and yet their coexpression has precluded understanding of the relative contribution of each CEACAM to functional responses of neutrophils during neisserial infection. In this work, we directly address the role of each CEACAM during infection by introducing individual human CEACAMs into a differentiated murine MPRO cell line-derived neutrophil model. Murine neutrophils cannot bind the human restricted Neisseria; however, we show that introducing any of the Opa-binding CEACAMs of human neutrophils (CEACAM1, CEACAM3, and CEACAM6) allows binding and entry of Neisseria into murine neutrophils. While CEACAM1- and CEACAM6-expressing neutrophils bind more bacteria, neisserial uptake via these two receptors unexpectedly proceeds without appreciable neutrophil activation. In stark contrast, neisserial engulfment via CEACAM3 recapitulates the oxidative burst and intracellular granule release seen during human neutrophil infection. Finally, by coexpressing multiple CEACAMs in our model, we show that the expression of CEACAM1 and CEACAM6 potentiate, rather than hinder, CEACAM3-dependent responses of neutrophils, exposing a cooperative role for this family of proteins during neisserial infection of neutrophils. These observations illustrate a divergence in function of CEACAMs in neutrophils and implicate the human-restricted CEACAM3 in the neutrophil innate response to neisserial infection. PMID- 22064718 TI - Injuries to individuals participating in mountain and wilderness sports: a review. AB - OBJECTIVE: The objective of this review is to summarize evidence on injuries occurring in individuals participating in mountain and wilderness sports. DATA SOURCES: Scopus, ISI Web of Knowledge, SPORTDiscus, Ovid Safety and Health, Index to Theses, COPAC, and sportscotland e-library. The search terms were (mountain* or wilderness or adventure or climb* or (hill walk*)) and (accident* or injur* or rescue*) and (epidemiolog* or statistic* or pattern* or survey*). The search period was from 1987 to 2010. STUDY SELECTION: A total of 2034 articles were identified. The full text of 137 articles was retrieved. Fifty articles met inclusion criteria-mountain and wilderness; nonmotorized, leisure time, outdoor activities; and nonfatal injury. Skiing and snowboarding articles were excluded. DATA EXTRACTION: Study design was classified using the "STOX" hierarchy of evidence. Study quality was rated independently by 2 reviewers. DATA SYNTHESIS: All studies were observational. Twenty-one (42%) were longitudinal, 20 (40%) were cross-sectional surveys, and 9 were cohort studies. A majority of casualties were aged 20 to 39 years. There was a clear male majority, 70% to 89% in most studies. The percentage of casualties who sustained severe injuries ranged from 5% to 10%- less than 10% were admitted to hospital. Casualties sustained an average of 1.2 to 2.8 injuries (most >1.6), which mainly affected the soft tissues; between 2% and 38% were fractures. Up to 90% of injuries were to the extremities. CONCLUSIONS: The majority of mountain and wilderness sports injuries are minor to moderate. However, some casualties have life-threatening medical problems, which may have long-term implications for return to sport and general well-being. PMID- 22064719 TI - Severe physical exertion, oxidative stress, and acute lung injury. AB - We report the case of a 27-year-old male athlete presenting with severe dyspnoea 24 hours after completing an "Ironman Triathlon." Subsequent chest radiology excluded pulmonary embolus but confirmed an acute lung injury (ALI). Echocardiography corroborated a normal brain natriuretic peptide level by demonstrating good biventricular systolic function with no regional wall motion abnormalities. He recovered well, without requiring ventilatory support, on supplemental oxygen therapy and empirical antibiotics. To date, ALI following severe physical exertion has never been described. Exercise is a form of physiological stress resulting in oxidative stress through generation of reactive oxygen/nitrogen species. In its extreme form, there is potential for an excessive oxidative stress response--one that overwhelms the body's protective antioxidant mechanisms. As our case demonstrated, oxidative stress secondary to severe physical exertion was the most likely factor in the pathogenesis of ALI. Further studies are necessary to explore the pathological consequences of exercise induced oxidative stress. Although unproven as of yet, further research may be needed to demonstrate if antioxidant therapy can prevent or ameliorate potential life-threatening complications in the acute setting. PMID- 22064720 TI - Topical nitroglycerin decreases pain intensity in daily activities: a review. AB - OBJECTIVE: To review the evidence for the effectiveness of topical nitroglycerin in treating acute and chronic tendinopathies among adults. DATA SOURCES: The investigators searched 27 databases for experimental studies, published from January 1990 to March 2009 in any language, on nitroglycerin application for tendon injuries. Further studies were sought from the reference lists of relevant articles. STUDY SELECTION: Selection criteria were randomized controlled trials (RCTs) and other clinical controlled trials that compared topical nitroglycerin with placebo, an alternative intervention, or a standard treatment for acute (<2 weeks), subacute (2-6 weeks), or chronic (>6 weeks) tendinopathy; adult participants; and reduction of pain as an outcome measure. The search identified 163 published articles, of which 7 RCTs were included. DATA EXTRACTION: Details of the study design, participants, interventions, and outcomes (primarily pain, and secondarily range of motion and strength of the involved musculotendinous units) were extracted. Quality was evaluated by the Standard Quality Assessment Criteria for Evaluating Research Papers (14 points, scored 2 for "yes" and 1 for "partial"). Data assessment was done by 2 independent reviewers. MAIN RESULTS: Glyceryl trinitrate was compared with placebo in 5 studies, 1 study compared nitroglycerin with local corticosteroid/anesthetic solution, and 1 study compared nitroglycerin and tendon rehabilitation with tendon rehabilitation alone. Dosage of transdermal nitroglycerin varied from 0.72 to 5 mg per day for a period of 3 days to 24 weeks. In the acute phase of tendinopathy, 2 studies reported conflicting evidence for pain relief, with the comparison between nitroglycerin and corticosteroid infiltration favoring the latter. In 2 studies, there was limited evidence for the effectiveness of nitroglycerin in improving joint mobility. In the chronic phase, 5 studies assessed pain intensity at rest, with activity, and/or at night. Meta-analysis of the results of 3 of the studies favored nitroglycerin over control for decreasing pain on activities of daily living [odds ratio (OR) 4.44; 95% confidence interval (CI) 2.34-8.40]. When results from the acute studies were included, the positive effects of nitroglycerin on pain intensity remained (OR, 4.86; 95% CI, 2.62-9.02). In chronic tendinopathies, evidence for decreasing pain at rest and during the night was conflicting. Pain duration and sleep-hour duration were not improved. There was limited evidence of improvement effected by transdermal nitroglycerin in range of motion and in local tenderness. Evidence from 3 studies showed an increase in peak muscle force after 24 weeks. All 7 studies reported headache as an adverse event, which resulted in 1 to 9 discontinuations of the intervention. Data from 4 studies found an increase in the incidence of headache with nitroglycerin (OR, 1.73; 95% CI, 1.01-2.97). Data from 3 studies showed no difference in the occurrence of contact dermatitis between nitroglycerin and placebo. Study quality was good (mean score, 23.71/28 points). Most of the studies passed the criteria pertaining to randomization, comparison of baseline characteristics, and appropriate methods of outcome evaluation and analysis. Blinding was infrequent or inadequate. CONCLUSIONS: Topical nitroglycerin relieved pain intensity in activities of daily living among patients with chronic or acute tendinopathies. There was little evidence for effectiveness on other outcomes. The incidence of headache was increased by nitroglycerin. PMID- 22064721 TI - Corticosteroid and other injections in the management of tendinopathies: a review. AB - OBJECTIVE: To determine the efficacy and risk of adverse effects of peritendinous corticosteroid and other injections in the management of tendinopathy. DATA SOURCES: In March 2010, using terms describing common tendinopathies and injections, including steroids, local anesthetics, sclerosing solutions, aprotinin, platelet-rich plasma, botulinum toxins, and glycosaminoglycans, 8 databases were searched without language, publication, or date restrictions. Reference lists were scanned for additional articles. STUDY SELECTION: Criteria for inclusion were randomized controlled trials that compared >=1 peritendinous injection with placebo or other nonsurgical intervention. Study methods were independently assessed by 2 reviewers (reliability, kappa = 0.85) on a modified PEDro scale, and scores were required to be >=50% for inclusion. Studies with a high proportion of patients with adhesive capsulitis, full-thickness rotator cuff tears, or rheumatologic disease were excluded. Of 2954 studies screened, 174 full text articles were evaluated for inclusion by 1 investigator and confirmed by a second. Of 64 studies that were initially included, the 41 that scored >50% on the PEDro scale were retained. DATA EXTRACTION: Information about injection type and comparison treatments, site of the tendinopathy, duration of follow-up (short term, <12 weeks; long term, >=52 weeks), outcomes (pain, function, and patient rated overall improvement), and frequency of adverse events was extracted. Study results were pooled when the data were sufficiently homogeneous. MAIN RESULTS: Clinically diagnosed lateral epicondylalgia: In 3 trials that compared corticosteroid injections with no intervention, corticosteroid injections were effective in the short term in pain reduction [standard mean difference (SMD), 1.44; 95% confidence interval (CI), 1.17-1.71], in improving function (SMD, 1.50; 95% CI, 1.22-1.77), and in overall improvement [relative risk (RR), 3.47; 95% CI, 2.11-5.69]. In the intermediate and long term, corticosteroid injections were less effective than no intervention. In comparison with placebo injection (4 studies), there was limited evidence for the effectiveness of corticosteroid injection in relieving pain. In comparison with physiotherapy (4 studies), corticosteroid injection was more effective in the short term for improving function (SMD, 1.29; 95% CI, 1.03-1.55) and in overall improvement (RR, 2.37; 95% CI, 1.75-3.21), and there was strong evidence among heterogeneous studies for reducing pain. Intermediate and long-term results were worse in pain and function for the corticosteroid injection intervention. Corticosteroid injections were more effective than orthotic devices for the wrist or elbow for overall improvement in the short term but not in the long term (2 studies). Effectiveness did not differ in comparisons of high- versus low-corticosteroid dosage, and between triamcinolone and hydrocortisone. Pain and function improved more with corticosteroid than with platelet-rich plasma injection in the short term but were worse in the long term. Rotator cuff tendinopathy: In the short term, corticosteroid injection improved pain (SMD, 0.68; 95% CI, 0.35-1.01) and function (SMD, 0.62; 95% CI, 0.29-0.95) more than placebo (3 studies). In comparisons with nonsteroidal anti-inflammatory drugs (NSAIDs) and with NSAIDs plus placebo injection, no differences in pain or function were found (3 studies) or when NSAIDs were administered in addition to corticosteroid and placebo injections (4 studies). Corticosteroid injection and physiotherapy did not differ in effectiveness (2 studies), although 1 study found short-term greater overall improvement and function after corticosteroid injection. Adverse effects were reported in 82% of corticosteroid injection trials. In comparison with placebo injections, corticosteroid injections were associated with an increased risk of atrophy for Achilles and patellar tendons but not elbow tendons. In trials of injections of sclerosant, platelet-rich plasma, proteinase, glycosaminoglycan polysulfate, sodium hyaluronate, prolotherapy, and botulinum toxin compared with placebo injection or other therapies, only sodium hyaluronate compared with placebo showed consistently better results in the short and long term in overall improvement and pain reduction of lateral epicondylalgia (1 study). Adverse effects were reported for all these injections except sclerosant and platelet rich plasma. CONCLUSIONS: Corticosteroid injection is beneficial in the short term for the treatment of tendinopathies but may be worse than other treatments in the intermediate and long terms. No clear evidence of benefit of other injections was shown, except for sodium hyaluronate in the short and long term. PMID- 22064722 TI - Ice slurry ingestion increases running time in the heat. AB - OBJECTIVE: To examine the effect of drinking an ice slurry (slushy) compared with cold water on prolonged submaximal exercise performed in the heat and on thermoregulatory responses. DESIGN: Crossover trial, with the 2 conditions counterbalanced and in random order. Results were adjusted for multiple comparisons by the method of Bonferroni. SETTING: Exercise laboratory study; Edith Cowan University, Western Australia. PARTICIPANTS: Moderately active male volunteers (n = 10; mean age, 28 years) who participated in recreational sport and who had no injuries or history of heat illness were included. INTERVENTION: Five to 14 days before the trials, the participants were familiarized with the procedure by a progressive treadmill run to volitional exhaustion at their previously determined first ventilatory threshold running speed, in the same hot environment as the trials (34 degrees C, 55% relative humidity). The 2 experimental trials were completed at the same time of day, 5 to 20 days apart. During the first 15 minutes, the participants rested while baseline measurements were taken. Over the next 30 minutes, they drank either a 7.5 g/kg flavored ice slurry (-1 degrees C) or the same volume of flavored cold water (4 degrees C) and then commenced the treadmill run. Participants were instructed to keep their normal lifestyle habits stable. In the 24 hours preceding the trials, they were asked to avoid strenuous exercise and to consume a specified amount of carbohydrate and fluid but no alcohol, caffeine, nonsteroidal anti-inflammatory drugs, or nutritional supplements. Urine and blood samples were taken, and respiratory variables, heart rate, and rectal and skin temperatures were continuously monitored. Heat storage was calculated from temperature and anthropomorphic measurements. MAIN OUTCOME MEASURES: The primary outcome measures were comparisons of run time to exhaustion, perceived exhaustion, heat storage capacity, and changes in rectal and skin body temperatures during the 2 trials. MAIN RESULTS: All 10 participants took longer to fatigue (range, 2.4-14.2 minutes) after ice slurry (mean, 50.2 minutes; SD, 8.5 minutes) than after cold water (mean, 40.7 minutes; SD, 7.2 minutes) ingestion (relative mean increase, 19%; SD, 6%; P = 0.001). Mean rectal temperature during the rest period did not differ between conditions but was 0.32 degrees C lower after drinking the ice slurry than after cold water ingestion before the start of exercise (P = 0.001). During the treadmill runs, rectal temperature rose for both conditions but remained lower for the ice slurry condition for the first 30 minutes of exercise (P = 0.001). After exercise to exhaustion, mean rectal temperature was higher for the ice slurry condition than for the cold water condition (39.36 degrees ; SD, 0.41 degrees vs 39.05 degrees ; SD, 0.37 degrees ; P = 0.001). Mean skin temperature showed a similar pattern to rectal temperature except that the conditions did not differ during or after exercise. During the prerun period, heat storage was lower after ice slurry than after cold water ingestion (-18.28 W/m vs -7.84 W/m; P = 0.001), but during exercise, heat storage was greater after ice slurry than after cold water ingestion (100.10 W/m vs 78.93 W/m; P = 0.005), although the mean rates of heat storage were similar between conditions. During exercise, participant ratings of thermal sensation and perceived exertion were lower after ice slurry than after cold water ingestion, except at exhaustion, when the ratings were similar. CONCLUSIONS: Ice slurry (slushy) compared with cold water ingestion prolonged running time to exhaustion in hot and humid conditions, reduced rectal temperature during exercise, and allowed rectal temperature to rise higher before the runner reached exhaustion. PMID- 22064723 TI - Promoting cycling: a review of interventions. AB - OBJECTIVE: To determine which approaches promote cycling, the size of the effects, and whether there are associated benefits on physical activity or anthropometric measures, by means of a systematic review. DATA SOURCES: Intervention studies with a cycling outcome measure were identified from searches of 13 databases, previous systematic reviews, Web sites, and reference lists of selected articles. International experts were asked to identify further relevant published or unpublished studies. The search was completed in January 2010. STUDY SELECTION: The selection criteria were controlled trials and "before and after" studies of the effect of any intervention on cycling behavior; studies had to include a minimal or no intervention comparison group or a similar population; and a specific measure of cycling before and after the intervention was required. Studies using stationary bicycles were excluded. Of 32,916 records retrieved, 118 full-text articles were assessed, and 25 were included in the quantitative analysis. Each step in the selection process was independently reviewed by a second reviewer, and disagreements were resolved. DATA EXTRACTION: Details of the study setting, objective, intervention, sample, duration, outcome measures, and results were extracted and checked by 2 reviewers, who also assessed validity (evaluated in summary as yes/no on randomization, representativeness, comparability, measurement, and use of statistical test). Disagreements were resolved by discussion. Outcomes were summarized as absolute changes in cycling after adjustment for changes in the control group. Meta-analysis was not possible because of heterogeneity and statistical inadequacies in the studies. MAIN RESULTS: Six studies [2 randomized controlled trials (RCTs), 1 cohort study, and 3 controlled repeat cross-sectional studies, all meeting >=3 validity criteria] included interventions primarily intended to promote cycling. An RCT using individual counseling and incentives as interventions found that Swedish women with abdominal obesity in the intervention group were more likely to report cycling >2 km per day after 18 months than the control group [odds ratio, 7.8; 95% confidence interval (CI), 4.0-15.0]. Increase in cycling was not associated with greater reductions in waist circumference in women in the intervention group than in the control group. A cluster RCT (Bike-Texas Safe Routes to School) using combined educational and promotional activities as interventions found no difference after 1 semester in cycling to school among fourth and fifth graders and their parents compared with control schools, but the prevalence of recreational cycling increased (net increase + 2.54 days per week; P = 0.02). In a controlled repeat cross-sectional study in the Netherlands, improving the connectivity of 1 area of Delft was associated with an increase from 40% to 43% in household cycle trips after 3 years, compared with a change from 38% to 39% in an unimproved area. In Odense, Denmark, promotion and improved infrastructure were associated, after 3 years, with a 3.4% net increase in bicycle trips (adjusted for regional trends). In a cohort study in Australia, residents in 1 area were encouraged by a wide-ranging promotional program, including cycle training and free bike hire, to use existing cycle paths. After 2 years, residents of the intervention area reported more use of the cycle paths than the comparison group (net change in prevalence, +5.1%; P < 0.01), and bicycle counters also showed greater cycle path use in the intervention area (net increase, 7.9%), but no increase in the prevalence of cycling in the population occurred. In English towns, media campaigns, services for cyclists, and improvements to infrastructure were associated with increased proportions of residents who reported cycling more frequently (net increase in proportions cycling >=12 times per month in 2 areas, 0.97% and 1.65%, and net increase in proportions cycling for >=30 minutes once per month, 2.78% and 1.89%) compared with control towns. There was a reduction in the proportion of residents in intervention areas who were classified as inactive (-2.6%; 95% CI, -3.7% to 1.5%), but no increase in the proportion who were more than moderately active. The effects of individualized marketing of walking, cycling, and public transit use as an alternative to car use were investigated in 16 studies (2 cohort studies and 14 controlled repeat cross-sectional studies; 13 studies met 2 validity criteria). Most studies included individualized information and incentives to households interested in changing their travel behavior and were associated with modest but generally consistent increases in self-reported cycling trip frequency (median, +8 trips per person per year; range, 0 to +21). CONCLUSIONS: Individual and community intervention programs, improving infrastructure, and marketing to households all increased cycling (usually self reported) to a small extent. Environmental changes combined with advice and support may be needed to increase cycling substantially and in a sustainable way in the population. PMID- 22064724 TI - In response to: SCUBA diving and portal vein thrombosis: a case report. PMID- 22064725 TI - In response to: Seventy-five percent of National Football League teams use pregame hyperhydration with intravenous fluid. PMID- 22064727 TI - Bupropion hydro-bromide propanol hemisolvate. AB - The title compound {systematic name: N-[1-(3-chloro-phen-yl)-1-oxopropan-2-yl] tert-butanaminium bromide propanol hemisolvate}, C(13)H(19)ClNO(+).Br( ).0.5C(3)H(8)O, crystallizes with two independent bupropion hydro-bromide ion pairs and a solvent 1-propanol mol-ecule in the asymmetric unit. In both mol ecules, the expected proton transfer from HBr to the amino group of the bupropion mol-ecule is observed, and intra- and inter-molecular N-H?Br hydrogen-bond inter actions are formed. These inter-actions link the mol-ecules into hydrogen-bond dimers. The side chains of the two cations have slightly different orientations. The 1-propanol solvent mol-ecule is linked to a bromide ion by an O-H?Br hydrogen bond. PMID- 22064728 TI - Bilateral hand malformations with absence of carpal bones with fusion of proximal metacarpals. AB - A 14-year-old boy presented with a deformity of his left hand since birth. His parents were nonconsanguineous and his early history was uneventful. The mother was not exposed to any teratogenic drugs during pregnancy. His other siblings are normal. The parents noticed the hand deformity at birth but he had not come to medical attention until he complained of restricted movement of the left hand at the wrist. On examination he did not have any pain on movement of the wrist nor tenderness over the wrist joint. Palmar flexion was restricted completely and active dorsiflexion was restricted in the last 30 degrees . Further passive dorsiflexion was exaggerated and the middle finger could touch the dorsal aspect of the forearm. The hand was deviated to the ulnar side. The patient was of normal stature and had no dysmorphic features. The index finger of the right hand was noted to be small. His feet were normal PMID- 22064729 TI - Pollicisation of the index finger without interosseous muscle or extensor tendon repositioning in isolated thumb hypoplasia/aplasia. AB - As a part of the pollicisation procedure, previous authors describe interosseous muscle and/or extensor tendon repositioning. The benefit of these tendon transfers has never been investigated despite the fact that other authors have used different techniques or do not perform some of these transfers routinely. In this paper, 16 children (17 hands) with isolated aplasia/hypoplasia of the thumb underwent the pollicisation procedure without any intrinsic tendon transfers. Surgery was performed at a mean age of 22 months and the mean follow-up time was 5 years. No early operative complications were seen. At final follow-up, the overall function and appearance of the hand was satisfactory in all patients. The results of our retrospective study warrant further investigation of these tendon transfers in a prospective comparative long-term study. PMID- 22064730 TI - Arthroscopic synovectomy of idiopathic synovitis of the distal radial ulnar joint. PMID- 22064731 TI - Accuracy of the skyline view for detecting dorsal cortical penetration during volar distal radius fixation. AB - Fractures of the distal radius are commonly treated using volar locking plates. Several complications have been associated with this procedure, including extensor tendon irritation and rupture. It has been suggested that prominence of screws past the dorsal cortex may contribute to this complication. This study aimed to determine the ability of the skyline view to demonstrate screws penetrating the dorsal cortex. A volar locking plate was applied to a synthetic forearm model. Lateral, oblique, and skyline views were obtained, with the distal screws both beneath and 1 mm beyond the dorsal cortex. The images were shown to orthopaedic trainees who were asked to decide if screws penetrated the dorsal cortex. Subjects were correct in 83% of cases using the skyline view compared with 77% (p = 0.05, lateral) and 50% (p < 0.01, oblique). This study demonstrates the skyline view of the distal radius could be a useful and accurate addition to routine intraoperative fluoroscopy views. PMID- 22064732 TI - (E)-4-Hy-droxy-N'-(3-hy-droxy-4-meth-oxy-benzyl-idene)benzohydrazide. AB - The mol-ecule of the title benzohydrazide derivative, C(15)H(14)N(2)O(4), exists in a trans conformation with respect to the C=N double bond and is twisted, the dihedral angle between the two benzene rings being 24.17 (6) degrees . The meth oxy group is almost co-planar with respect to the attached benzene ring [C(m)-O-C C (m = meth-yl) = -1.45 (17) degrees ]. In the crystal, the mol-ecules are linked by N-H?O and O-H?O hydrogen bonds into sheets parallel to the bc plane. These sheets are further connected into a three-dimensional network by weak C-H?O and C H?pi inter-actions. PMID- 22064733 TI - Effects of supplementation frequency on ruminal fermentation and digestion by steers fed medium-quality hay and supplemented with a soybean hull and corn gluten feed blend. AB - Reducing the frequency of supplementation to beef cattle would reduce labor and vehicle maintenance costs and could have the potential to increase profits if performance is not negatively affected. Six ruminally cannulated beef steers (362 +/- 18 kg of BW) were used in a replicated 3 * 3 Latin square design to determine the effect of supplementation frequency (daily or on alternate days) on digestion and ruminal parameters when feeding medium-quality hay and supplementing with a mixture of soybean hulls and corn gluten feed. Dietary treatments consisted of ad libitum fescue hay (8.8% CP and 34.8% ADF) that was supplemented at 1% of BW daily (SD), supplemented at 2% of BW on alternate days (SA), or not supplemented (NS). The supplement (14.6% CP and 29.8% ADF) contained 47% soybean hull pellets, 47% corn gluten feed pellets, 2% feed grade limestone, and 4% molasses (as fed). Each period consisted of a 12-d adaptation phase followed by 6 d of total fecal, urine, and ort collection. All supplement offered was consumed within 2 h. Ruminal fluid was collected every 4 h for 2 d. Hay intake was reduced (P < 0.01) for SD and further reduced (P < 0.01) for SA. Hay intake was 1.54, 1.19, and 1.02% of BW (SEM +/- 0.036) for NS, SD, and SA, respectively. There was a treatment (P < 0.01) * day interaction for mean ruminal pH. On the day of supplementation, ruminal pH for SA (6.13) was lower (P < 0.01) than those for both SD (6.29) and NS (6.52). However, on the day the SA treatment did not receive supplement, ruminal pH of SA (6.53) did not differ (P = 0.87) from ruminal pH of NS and was greater (P < 0.01) than that of SD. Ruminal pH of SD was lower (P < 0.01) than that of NS. Diet DM digestibility was increased (P < 0.01) by supplementation but did not differ (P = 0.58) because of frequency. Dry matter digestibility was 57.9, 64.1, and 64.6% (SEM +/- 0.65) for NS, SD, and SA, respectively. The amount of N retained did not differ (P = 0.47) because of frequency (24.9 +/- 5.61 and 22.0 +/- 5.50 g/d for SD and SA, respectively) and was greater (P < 0.01) for the supplemented treatments than for NS (4.2 +/- 3.30 g/d). When supplementing a blend of soybean hulls and corn gluten feed, producers can reduce the frequency of supplementation to every other day without reducing digestibility or N retention. PMID- 22064734 TI - Amino acid digestibility of corn distillers dried grains with solubles, liquid condensed solubles, pulse dried thin stillage, and syrup balls fed to growing pigs. AB - Distillers dried grains with solubles (DDGS) has low and variable AA digestibility. The variability is often attributed to damage during the heating process, and it has been suggested that the damage happens to the soluble components of DDGS such as reducing sugars. Combining solubles and grains sometimes produces syrup balls (SB); their digestibility is unknown. The objective of this experiment was to identify potential sources of poor and variable AA digestibility in DDGS. Specifically, our objective was to determine whether the problems are associated with the solubles component or with SB. The ingredients evaluated were DDGS, intact SB, ground SB, liquid condensed solubles (LCS), and pulse dried thin stillage (PDTS) obtained from the same ethanol plant. The LCS is produced by evaporation of thin stillage. Each ingredient was used as the only source of AA in an experimental diet. In a duplicate 6 * 6 Latin square design with 7-d adaptation and collection periods, the 6 treatments consisted of an N-free diet and the 5 test ingredients. Pigs had 5 d of adaptation to each diet, and on d 6 and 7 ileal digesta were collected from an ileal cannula for 8 h each day. Both SB treatments had apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of AA that were similar or greater (P < 0.05) than those of DDGS. The AID and SID values of Lys and a few other AA were similar in LCS (SID Lys: 63.1%) and DDGS (SID Lys: 61.5%), but the digestibility values of most AA in LCS were less than in DDGS (P < 0.05). The low digestibility of AA in LCS was most pronounced for Met (SID: LCS, 41.9% vs. DDGS, 82.8%). The LCS had less (P < 0.05) AID and SID of CP (SID: 67.8%) than intact SB (SID: 85.2%) and ground SB (SID: 85.9%) as well as all AA. The PDTS generally had the least AID and SID and had less (P < 0.05) CP (SID: 55.3%) and several AA, including Lys, compared with LCS. In conclusion, the presence of SB does not decrease AA digestibility of DDGS, and the LCS evaluated has less indispensible AA digestibility than DDGS. The LCS has low digestibility of AA that seems to not be caused by heat damage. PMID- 22064735 TI - Granulated lysozyme as an alternative to antibiotics improves growth performance and small intestinal morphology of 10-day-old pigs. AB - Lysozyme is a 1,4-beta-N-acetylmuramidase that has antimicrobial properties. The objective of this experiment was to determine the effect of a purified granulated lysozyme, compared with antibiotics, on growth performance, small intestinal morphology, and Campylobacter shedding in 10-d-old pigs. Forty-eight pigs (n = 16 per treatment), with an initial BW of 4.0 +/- 0.1 kg (P > 0.40), were weaned at 10 d of age, blocked by litter and sex, and assigned to pens (8 pigs/pen). Each block was randomly assigned to consume 1 of 3 liquid dietary treatments for 14 d: a control diet, the control diet + lysozyme (100 mg/kg of diet), or the control diet + antibiotics (neomycin and oxytetracycline, 16 mg/kg of diet). Pigs were weighed and blood was sampled on d 0, 7, and 14. Blood was analyzed for plasma urea N and IgA. After 14 d of treatment, pigs were killed and samples of the jejunum and ileum were collected and fixed to measure villus height and crypt depth. Rectal swabs were taken on d 0, 7, and 14 of treatment, and samples of ileal and cecal contents were taken at d 14 of treatment to determine the presence of Campylobacter. Pigs consuming lysozyme and antibiotics gained BW at a faster rate than did control pigs over the course of the study (402 +/- 12 and 422 +/- 14 g/d, respectively, vs. 364 +/- 14 g/d; P < 0.02), resulting in heavier ending BW (9.9 +/- 0.3, 9.9 +/- 0.3, and 9.0 +/- 0.2 kg for pigs in the lysozyme, antibiotic, and control groups, respectively; P < 0.03). Immunoglobulin A decreased and plasma urea N increased over the course of the study (P < 0.1), regardless of dietary treatment (P > 0.6). Crypt depth was increased in pigs fed lysozyme- and antibiotic-treated diets, compared with pigs fed the control diet, in both the jejunum (60.0 +/- 2.8 and 62.2 +/- 3.0 um, respectively, vs. 50.7 +/- 3.1 um; P < 0.03) and ileum (76.0 +/- 7.5 and 72.2 +/- 5.0 um, respectively, vs. 52.4 +/- 3.5 um; P < 0.02). Villus height did not differ in the jejunum (P > 0.2) but was increased in the ileum of pigs consuming the lysozyme- and antibiotic treated diets, compared with pigs fed the control diet (312 +/- 20 and 314 +/- 10 um, respectively, vs. 263 +/- 15 um; P < 0.4). Small intestinal total mucosa and mucosal protein concentrations, as well as disaccharidase-specific activities, were not altered by lysozyme or antibiotics (P > 0.05). Campylobacter was detected in 27% of control samples but in only 5% of samples from pigs fed antibiotics and 8% of samples from pigs fed lysozyme (P < 0.01). Thus, granulated lysozyme is a suitable alternative to antibiotics for 10-d-old pigs consuming manufactured liquid diets. PMID- 22064736 TI - Triennial Lactation Symposium: Effects of stress on postpartum reproduction in dairy cows. AB - The objective was to review the effects of production stressors on reproductive performance of dairy cows. It has been well documented that genetic selection for milk yield over the last 50 yr has been associated with reduced fertility. In addition to negative associations between yield and conception rate, there is also an association between milk production and expression of behavioral estrus. Stress caused by production diseases in high-yielding dairy cows also contributes to the problems of poor fertility. Lameness results in reduced intensity of estrus and can contribute to ovulation failure, which is largely due to reduced pre-ovulatory estradiol secretion and failure of the LH surge. Mastitis has been associated with prolonged intervals to dominant follicle selection, and in animals with uterine infection the dominant follicle grows slower and produces less estradiol. In a recent study, we identified that milk yield was associated with an increased incidence of uterine infection, which is known to contribute to reduced fertility and prolonged calving-to-conception intervals. The incidence of uterine disease was 73% in high-yielding, compared with 45% in low-yielding cows. As well as effects at the ovary, various models of stress have also been shown to perturb endocrine secretion in the hypothalamus and anterior pituitary. In conclusion, the adverse effects on fertility associated with genetic selection for yield in dairy cows is, in part, associated with increased incidences of production disease-induced stress but is also associated with high milk yield. PMID- 22064737 TI - Use of rosemary, oregano, and a commercial blend of essential oils in broiler chickens: in vitro antimicrobial activities and effects on growth performance. AB - The present study was conducted to characterize the in vitro antimicrobial activities of 3 essential oils [oregano, rosemary, and a commercial blend of essential oils (BEO)] against pathogenic and nonpathogenic bacteria and to evaluate their effects on broiler chicken performances. The chemical composition of the essential oils was determined using the gas chromatography interfaced with a mass spectroscopy. The disc diffusion method, the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC) were applied for the determination of antimicrobial activities of essential oils. In vivo study, a total of seven hundred fifty 1-d-old male broiler chickens were assigned to 6 dietary treatment groups: basal diet (control; CON), CON + 44 mg of avilamycin/kg (A), CON + 100 mg of rosemary essential oil/kg (ROS), CON + 100 mg of oregano essential oil/kg (OR), CON + 50 mg of rosemary and 50 mg of oregano essential oils/kg (RO), and CON + 1,000 mg of BEO/kg (essential oil mixture, EOM). The essential oils isolated from rosemary and oregano were characterized by their greater content of 1,8-cineole (49.99%) and carvacrol (69.55%), respectively. The BEO was mainly represented by the aldehyde (cinnamaldehyde) and the monoterpene (1,8-cineole) chemical groups. The results of the disc diffusion method indicated that the rosemary essential oil had antibacterial activity (P <= 0.05) against only 3 pathogenic bacteria, Escherichia coli (8 mm), Salmonella indiana (11 mm), and Listeria innocua (9 mm). The essential oil of oregano had antimicrobial activities (P <= 0.05) on the same bacteria as rosemary but also on Staphylococcus aureus (22 mm) and Bacillus subtilis (12 mm). Oregano essential oil had greater (P <= 0.05) antimicrobial activities against pathogenic bacteria than rosemary essential oil but they had no synergism between them. The BEO showed an increased antimicrobial activity (P <= 0.05) against all studied bacteria (pathogenic and nonpathogenic bacteria) except for Lactobacillus rhamnosus. The supplementation of the basal diet with avilamycin or essential oils improved (P <= 0.05) broiler chicken BW, BW gain, and G:F compared with the CON diet. There were no differences in growth performances among birds fed A, ROS, OR, RO, or EOM diets. In general, essential oils contained in rosemary, oregano, and BEO can substitute for growth promoter antibiotics. Although the 3 essential oils had different antimicrobial activities, they exhibited the same efficiency in broiler chickens. PMID- 22064738 TI - Determining the optimal age for recording the retinal vascular pattern image of lambs. AB - Newborn Ripollesa lambs (n = 143) were used to assess the optimal age at which the vascular pattern of the retina can be used as a reference for identification and traceability. Retinal images from both eyes were recorded from birth to yearling (d 1, 8, 30, 82, 180, and 388 of age) in duplicate (2,534 images) using a digital camera specially designed for livestock (Optibrand, Fort Collins, CO). Intra- and inter-age image comparisons (9,316 pairs of images) were carried out, and matching score (MS) was used as the exclusion criterion of lamb identity (MS <70). Retinal images were used for verifying the identity of live lambs of 4 Spanish commercial categories: milk-fed lambs (MF; "lechal," 1 mo of age and <12 kg of BW, n = 136); light fattened lambs (LF; "recental," 3 mo of age and ~25 kg of BW, n = 134); recruited replacement lambs (RR; "ovino mayor," 6 mo of age and ~35 kg of BW, n = 59); and yearling replacement lambs (YR; >12 mo of age and ~50 kg of BW, n = 25). Values of MS were treated with a model based on the 1-inflated bivariate beta distribution, and treated data were compared by using a likelihood ratio test. Intra-age image comparisons showed that average MS and percentage of images with MS >=70 increased (P < 0.05) with lamb age from d 1 to 82 (81.0 +/- 1.0 to 95.9 +/- 0.4, and 75.8 to 100%, respectively) and reached a plateau thereafter. Inter-age retinal image comparisons for MF lambs at 30 d showed that the percentage of images with MS >=70 was greater when reference images at 8 d were used instead of 1-d images (94.8 vs. 87.4%, respectively; P < 0.05). In LF lambs, 30-d retinal images matched better than those at 8 d of age (99.6 vs. 93.6%, respectively; P < 0.05). Regarding RR and YR lambs, the 82-d images allowed the confirmation of 100% lamb identity, whereas 8-d images showed a smaller (P < 0.05) percentage of matching (87.9 and 89.8%, respectively, for RR and YR lambs; P > 0.05); no differences were detected for 30-d images (97.4 and 98.0%, respectively, for RR and YR lambs; P > 0.05). Total percentage of matching was achieved when images were obtained from older lambs (180 and 388 d). In conclusion, retinal imaging was a useful tool for verifying the identity and auditing the traceability of live lambs from suckling to yearling. Matching scores were satisfactory when the reference retinal images were obtained from 1 mo-old or older lambs. PMID- 22064739 TI - Field testing of a system for online classification of beef carcasses for longissimus tenderness using visible and near-infrared reflectance spectroscopy. AB - The present experiments were conducted to field test a system optimized for online prediction of beef LM tenderness based on visible and near-infrared (VISNIR) spectroscopy and to develop and validate a model for prediction of tenderness that would be unbiased by normal variation in bloom time before application of VISNIR. For both Exp. 1 and 2, slice shear force (SSF) was measured on fresh (never frozen) steaks at 14 d postmortem. Carcasses with VISNIR predicted SSF <=15 kg were classified as VISNIR predicted tender and carcasses with VISNIR-predicted SSF >15 kg were classified as VISNIR not predicted tender. In Exp. 1, spectroscopy was conducted online, during carcass grading, at 3 large scale commercial fed-beef processing facilities. Each carcass (n = 1,155) was evaluated immediately after ribbing and again when the carcass was graded. For model development and validation, carcasses were blocked by plant and observed SSF. One-half of the carcasses (n = 579) were assigned to a calibration data set, which was used to develop regression equations, and one-half of the carcasses (n = 576) were assigned to a prediction data set, which was used to validate the regression equations. Carcasses predicted tender by VISNIR spectroscopy had smaller (P < 10(-19)) mean LM SSF values at 14 d postmortem in the calibration (13.9 vs. 16.5 kg) and prediction (13.8 vs. 16.4 kg) data sets than did carcasses not predicted tender by VISNIR spectroscopy. Relative to carcasses not predicted tender by VISNIR, a decreased percentage of carcasses predicted tender by VISNIR had LM SSF >25 kg in the calibration (2.0 vs. 7.8%) and prediction (0.8 vs. 8.0%) data sets. In Exp. 2, carcasses (n = 4,204) were evaluated with VISNIR online at 6 commercial fed-beef processing facilities on 38 production days. The carcasses predicted tender by VISNIR spectroscopy had decreased mean LM SSF values at 14 d postmortem (16.3 vs. 19.9 kg; P < 10(-87)), longer sarcomere lengths (1.77 vs. 1.72 um; P < 10(-10)), and a greater percentage of desmin degraded (42 vs. 34%; P < 10(-5)) by 14 d postmortem. Relative to carcasses not predicted tender by VISNIR, a decreased percentage of carcasses predicted tender by VISNIR had LM SSF >25 kg (4.9 vs. 21.3%). The present experiments resulted in development and independent validation of a robust method to noninvasively predict LM tenderness of grain-fed beef carcasses. This technology could facilitate tenderness-based beef merchandising systems. PMID- 22064740 TI - Evaluation of a ruminally dosed tall fescue seed extract as a model for fescue toxicosis in steers. AB - Tall fescue (Lolium arundinaceum) toxicosis research is often complicated by a reduction in intake of infected forage or seed, making treatment comparisons difficult. This study was conducted to develop a fescue toxicosis model that would allow for variations in DMI without altering the quantity of alkaloids consumed over the course of the experiment. Ground tall fescue seed and a tall fescue seed extract were used in two 2-period crossover experiments to determine the effectiveness of ruminal dosing of a tall fescue seed extract to induce fescue toxicosis. This experiment used 4 growing Holstein steers (BW = 337 +/- 24 kg) surgically fitted with ruminal cannulas. Steers were maintained on a diet of endophyte-free fescue hay fed ad libitum throughout the experiment. Endophyte infected (E+; 4.1 mg/kg of ergovaline) and uninfected (E-; 0.0 mg/kg of ergovaline) KY-31 tall fescue seed was ground and dosed or extracted with ethanol, concentrated, and lyophilized before ruminal dosing. Ergovaline concentration of the final extract was 102 mg/kg. Animals were given a minimum of a 3-wk washout period between treatments. Physiological indicators were measured over 7 d at 22 degrees C (d 1 to 3) and 32 degrees C (d 4 to 7) during both seed and extract dosing. Seed and extract E+ dosing reduced serum prolactin concentrations such that they were not different from zero (P < 0.10). Treatment with E+ reduced feed intake (P < 0.05) and heart rate (P < 0.001), and increased respiration rate (P < 0.01) and core temperature (P < 0.05) during both seed and extract dosing. Increasing environmental temperature from 22 to 32 degrees C reduced total intake (P < 0.05) and increased core temperature (P < 0.001) and respiration rate (P < 0.001) during both seed and extract dosing. Diastolic blood pressure tended (P < 0.09) to be increased during E+ extract dosing and reduced during heat stress. These physiological alterations are consistent with those reported for cattle grazing or consuming seed from endophyte-infected tall fescue. These data indicate that a ruminally dosed ethanol extract of tall fescue seed is efficacious in inducing fescue toxicosis in cattle. PMID- 22064741 TI - Technical note: validation of a model for online classification of US Select beef carcasses for longissimus tenderness using visible and near-infrared reflectance spectroscopy. AB - The present experiment was conducted to provide a validation of a previously developed model for online classification of US Select carcasses for LM tenderness based on visible and near-infrared (VISNIR) spectroscopy and to determine if the accuracy of VISNIR-based tenderness classification could be enhanced by making measurements after postmortem aging. Spectroscopy was conducted online, during carcass grading, at a large-scale commercial fed beef processing facility, and the strip loin was obtained from the left side of US Select carcasses (n = 467). Slice shear force (SSF) was measured on fresh steaks at 2 and 14 d postmortem. Online VISNIR tenderness classes differed in mean SSF values at both 2 d (29.4 vs. 33.6 kg) and 14 d (18.0 vs. 21.2 kg) postmortem (P < 10(-7)). Online VISNIR tenderness classes differed in both the percentage of carcasses with LM SSF values greater than 40 kg at 2 d postmortem (5.1 vs. 21.0%; P < 10(-6)) and the percentage of carcasses with LM SSF values greater than 25 kg at 14 d postmortem (6.8 vs. 23.2%; P < 10(-5)). Whereas 15.0% of the carcasses sampled for this experiment had LM SSF values greater than 25 kg at 14 d postmortem, only 6.8% of the carcasses classified as tender by VISNIR had LM SSF values greater than 25 kg. All the carcasses sampled that had LM SSF values greater than 35 kg at 14 d postmortem were accurately classified as tough by VISNIR. Before measurement of SSF on d 14, VISNIR spectroscopy was conducted on the SSF steak. Tenderness classes based on d 14 VISNIR spectra differed both in mean SSF value at 14 d postmortem (17.7 vs. 21.6 kg; P < 10(-11)) and the percentage of carcasses with LM SSF values greater than 25 kg at 14 d postmortem (7.3 vs. 22.7%; P < 10(-5)). These data support our previous work showing that VISNIR spectroscopy can be used to classify US Select carcasses noninvasively for LM tenderness, and the results establish that this technology could also be applied to aged US Select strip loins. This technology would allow packing companies and other segments of the beef marketing chain to identify US Select carcasses or strip loins that excel in LM tenderness for use in branded beef programs. PMID- 22064742 TI - Characterization of L-lysine transport across equine and porcine jejunal and colonic brush border membrane. AB - In nonruminant herbivores, microbially derived AA could contribute to whole-body AA homeostasis and thus decrease predicted AA requirements. However, postileal capacity of AA uptake is currently unknown. Therefore, to test the hypothesis that Lys is transported across the large colon mucosal apical membrane with capacity similar to that of the small intestinal mucosa in the pony and pig, we examined Lys transport in vitro using brush border membrane vesicles (BBMV). Mucosa was collected from the distal jejunum (DJ) and proximal large colon (PLC) of growing pigs (n = 3) and ponies (n = 4), flash frozen in liquid nitrogen, and stored at -80 degrees C. Jejunal and colonic BBMV were manufactured by Mg(2+) precipitation and used to determine initial rates and kinetics [the maximal transport rate (V(max)) and the Michaelis constant (K(M))] of l-Lys transport into apical epithelia by rapid filtration technique in Na(+)-gradient incubation buffer. Initial rates of total l-Lys uptake did not differ between the PLC and DJ in either the pig or the pony, or between the pony and the pig, at each l-Lys concentration. In the pig, compared with the DJ, l-Lys transport V(max) in the PLC did not differ (121 +/- 26 and 180 +/- 26 pmol*mg of protein(-1)*s(-1), respectively; P = 0.14) and l-Lys K(M) in the PLC tended to be greater (0.23 +/- 0.22 and 0.89 +/- 0.22 mM, respectively; P = 0.09). In the pony, compared with the DJ, l-Lys transport V(max) in the PLC was greater (62 +/- 25 and 149 +/- 25 pmol*mg of protein(-1)*s(-1), respectively; P = 0.04) and l-Lys K(M) in the PLC was greater (0.08 +/- 0.22 and 1.05 +/- 0.22 mM, respectively; P = 0.02). l Lysine diffusion was not different between segments; however, total intestinal diffusion was greater (P = 0.03) in the pony than in the pig (115 +/- 10 and 73 +/- 10 pmol.mg of protein(-1)*s(-1), respectively). These results demonstrate that the large colon is capable of l-Lys transport across the apical epithelial membrane with greater capacity and less affinity than the jejunum, indicating that the large colon may play a significant role in l-Lys absorption and homeostasis in hindgut fermenters. PMID- 22064743 TI - Application of computer-assisted semen analysis to explain variations in pig fertility. AB - Sperm quality is often evaluated through computer-assisted semen analysis (CASA) and is an indicator of boar fertility. The aim of this research was to study the relationship between CASA motility parameters and fertility results in pigs. Insemination records and semen parameters from a total of 45,532 ejaculates collected over a 3-yr period were used. The statistical model for analysis of fertility data from these inseminations included factors related to sow productivity. The boar- and semen-related variance (direct boar effect) were corrected for the effects of individual boar, genetic line of the boar, age of the boar, days between ejaculations, number of sperm cells in an ejaculate, number of sperm cells in an insemination dose, and AI station. The remaining variance was analyzed if semen motility parameters had a significant effect. This analysis revealed significant (P < 0.05) effects of progressive motility, velocity curvilinear, and beat cross frequency on farrowing rate (FR). Total motility, velocity average path, velocity straight line, and amplitude of lateral head displacement affected (P < 0.05) total number of piglets born (TNB). Boar- and semen-related parameters explained 5.3% of the variation in FR and 5.9% of the variation in TNB. Motility parameters, measured by CASA, explained 9% of the boar- and semen-related variation in FR and 10% of the boar- and semen-related variation in TNB. Individual boar and genetic line of the boar affected (P < 0.0001) the variation in FR and TNB. No differences (P > 0.05) were observed between effects of AI stations on fertility outcome, underscoring the objectivity of the CASA system used. Motility parameters can be measured with CASA to assess sperm motility in an objective manner. On the basis of the motility pattern, CASA enables one to discriminate between the fertilizing capacity of ejaculates, although this depends on the genetic line of the boar used in AI stations. PMID- 22064744 TI - Spoilage characteristics of traditionally packaged ground beef with added lactic acid bacteria displayed at abusive temperatures. AB - Growth of pathogenic organisms such as Escherichia coli O157:H7 and Salmonella spp. can be inhibited in ground beef through the addition of certain lactic acid producing bacteria (LAB; Lactobacillus acidophilus NP51, Lactobacillus crispatus NP35, Pediococcus acidilactici, and Lactococcus lactis ssp. lactis). This study evaluated the effects of LAB inclusion on the organoleptic and biochemical properties typically associated with spoilage in traditionally packaged ground beef displayed at abusive (10 degrees C) temperatures for 36 h. Trained and untrained panelist evaluations of lean color and off-odor, as well as instrumental color analyses, did not indicate an effect on spoilage traits due to LAB utilization (P > 0.05). However, display length affected each variable independently and was indicative of decreased stability and acceptability as display time (h) increased (P < 0.05). Thiobarbituric acid values were decreased for ground beef with added LAB (P < 0.05), but likely can be related to bacterial degradation of lipid oxidation by-products because no reduction in organoleptic traits due to oxidation was noted between treatments. Overall, LAB did not adversely influence the spoilage characteristics of traditionally packaged ground beef displayed at abusive temperatures for up to 36 h. Furthermore, biochemical and sensory indicators of spoilage were present for all treatments at the conclusion of display. Therefore, LAB can be added to ground beef in traditional packaging as a processing intervention without masking or delaying the expected spoilage characteristics. PMID- 22064748 TI - (5S,6R)-6-Bromo-6-methyl-5-phenyl-3,4,5,6-tetra-hydro-2H-cyclo-penta-[b]pyran-7 one. AB - The title compound, C(15)H(15)BrO(2), was synthesized by a Bronsted acid catalysed domino electrocyclization-halogenation reaction. The five-membered ring is essentially planar (r.m.s. deviation 0.006 A) and forms a dihedral angle of 72.7 (3) degrees with the attached phenyl ring. The six-membered heterocycle adopts a half-chair conformation. The crystal packing is stabilized by a C-H?O contact. PMID- 22064745 TI - The effect of intravenous insulin infusion on renal blood flow in conscious sheep is partially mediated by nitric oxide but not by prostaglandins. AB - To test the effect of insulin on renal perfusion and the participation of NO and PG as mediators of this response, renal blood flow (RBF) was measured in sheep (n = 8) implanted with ultrasonic flow probes around renal arteries and with a systemic arterial pressure (SAP, n = 4) telemetry device. Three protocols were performed: 1) RBF and SAP were recorded (0800 to 1800 h) in fed and fasted sheep, with the latter receiving intravenous (i.v.) infusions (0.5 mL/min) of insulin at 2 or 6 mU/(kg.min); 2) fasted sheep received i.v. infusions of either an inhibitor of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME) alone [0.22 mg/(kg.min), 1000 to 1200 h] or L-NAME (1000 to 1200 h) + insulin during the second hour (6 mU/(kg.min), 1100 to 1200 h); and 3) the same protocol was followed as in protocol 2, substituting L-NAME with ketoprofen [0.2 mg/(kg.min)], a cyclooxygenase inhibitor. In all protocols, plasma insulin and glucose were determined. During insulin administration, euglycemia was maintained and hypokalemia was prevented by infusing glucose and KCl solutions. After the onset of meals, a long-lasting 18% increase in RBF and a 48% insulin increase were observed (P < 0.05), without changes in SAP. Low- and high-dose insulin infusions increased RBF by 19 and 40%, respectively (P < 0.05). As after meals, the increases in RBF lasted longer than the insulin increase (P < 0.05). The L-NAME infusion decreased RBF by 15% (P < 0.05); when insulin was added, RBF increased to preinfusion values. Ketoprofen decreased RBF by 9% (P < 0.05); when insulin was added, RBF increased to 13% above preinfusion values (P < 0.05). In no case was a modification in SAP or glucose noted during the RBF changes. In conclusion, insulin infusion mimics the meal-dependent increase in RBF, independent of SAP, and lasts longer than the blood insulin plateau. The RBF increase induced by insulin was only partially prevented by L-NAME. Ketoprofen failed to prevent the insulin-dependent RBF increase. Both facts suggested that complementary vasodilatatory agents accounted for the insulin effect on sheep renal hemodynamics. PMID- 22064749 TI - Diaqua-bis-(4-bromo-benzoato-kappaO)bis-(N,N-diethyl-nicotinamide kappaN)manganese(II). AB - In the crystal structure of the title Mn(II) complex, [Mn(C(7)H(4)BrO(2))(2)(C(10)H(14)N(2)O)(2)(H(2)O)(2)], the Mn(II) cation is located on an inversion center and coordinated by two diethyl-nicotinamide (DENA) ligands, two 4-bromo-benzoate (PBB) anions and two water mol-ecules in a distorted octa-hedral geometry. The dihedral angle between the carboxyl-ate group and the adjacent benzene ring is 3.25 (14) degrees . In the mol-ecule, the pyridine ring and the benzene ring are oriented at a dihedral angle of 77.24 (5) degrees . In the crystal, inter-molecular C-H?O hydrogen bonds link the mol ecules into a two-dimensional network. Weak inter-molecular C-H?O hydrogen bonds and pi-pi inter-actions between the pyridine rings of neighbouring mol-ecules [centroid-centroid distance = 3.537 (1) A] further consolidate the crystal packing. PMID- 22064750 TI - Spiro-[cyclo-propane-1,3'-indolin]-2'-one. AB - In the title mol-ecule, C(10)H(9)NO, the dihedral angle between the mean plane of the cyclo-propane ring and the essentially planar [maximum deviation = 0.032 (2) A] indole ring system is 87.65 (17) degrees . In the crystal, inter-molecular N H?O hydrogen bonds link mol-ecules into one-dimensional chains along [100]. PMID- 22064751 TI - Predictive role of nasal functionality tests in the evaluation of patients before nocturnal polysomnographic recording. AB - Obstructive sleep apnoea syndrome is a disease characterized by a collapse of the pharyngeal airway resulting in repeated episodes of airflow cessation, oxygen desaturation, and sleep disruption. It is a common disorder affecting at least 2 4% of the adult population. The role of nasal resistance in the pathogenesis of sleep disordered breathing and sleep apnoea has not been completely clarified. Aim of the present study was to establish whether nasal resistance and nasal volumes, measured by means of Active Anterior Rhinomanometry and Acoustic Rhinometry together with Muco-Ciliary Transport time play a positive predictive role in the evaluation of Obstructive sleep apnoea syndrome patients before running a nocturnal polysomnographic recording. A retrospective study was performed analysing 223 patients referred for suspected Obstructive sleep apnoea syndrome. All patients were submitted to complete otorhinolaryngological evaluation and underwent nocturnal polysomnography. On the basis of polysomnographic data analysis, the apnoea-hypopnoea index and snoring index, patients were classified into two groups: Group 1 (110/223 patients) with a diagnosis of mild-moderate Obstructive sleep apnoea syndrome (apnoea-hypopnoea index < 30) and Group 2 (113/223 patients) affected by snoring without associated hypoxaemia/hypercapnia. A control group of 76 subjects, not complaining of sleep disorders and free from nasal symptoms was also selected. The results showed, in all the snoring and Obstructive sleep apnoea syndrome patients, total nasal resistance and increased Muco-Ciliary Transport time compared to standard values. Furthermore, the apnoea-hypopnoea index was significantly higher in patients with higher nasal resistence and significantly different between the groups. These results allow us to propose the simultaneous evaluation of nasal functions by Active Anterior Rhinomanometry, Acoustic Rhinometry, and Muco-Ciliary Transport time in the selection of patients undergoing polysomnography. PMID- 22064752 TI - N-(4-Amino-phen-yl)-4-methylbenzene-sulfonamide. AB - The title compound, C(13)H(14)N(2)O(2)S, crystallized with two independent mol ecules in the asymmetric unit. They both have V-shaped conformations: the dihedral angles between their benzene rings are identical [45.86 (13) degrees ] and their C-S-N-C torsion angles are similar [67.9 (3) and 70.2 (3) degrees ]. In the crystal, the mol-ecules are linked by N-H?O and N-H?N hydrogen bonds, generating a three-dimensional network. PMID- 22064753 TI - 3-(4-Chloro-benzene-sulfonamido)-5-methyl-cyclo-hex-2-en-1-one. AB - For the title compound, C(13)H(14)ClNO(3)S, geometrical parameters, determined using X-ray diffraction techniques, are compared with those calculated by density functional theory (DFT), using hybrid exchange-correlation functional, B3LYP methods. The dihedral angle between the benzene ring and the conjugated part of the cyclo-hexene ring is 87.47 (5) degrees . The cyclo-hexene ring and its substituents are disordered over two conformations, with occupancies of 0.786 (3) and 0.214 (3). In the crystal, mol-ecules are linked into chains in the c-axis direction by inter-molecular N-H?O(C=O) hydrogen bonds. C-H?O inter-actions are also observed. PMID- 22064754 TI - Bis(1-benzyl-3-methyl-imidazolium-kappaC)mercury(II) bis-(hexa fluoridophosphate). AB - The asymmetric unit of the title complex, [Hg(C(11)H(12)N(2))(2)](PF(6))(2), consists of one bis-(1-benzyl-3-methyl-imidazolium)mercury(II) cation, one half of the cation and an additional Hg(II) atom, which lies on an inversion centre, and three hexa-fluorido-phosphate anions. The Hg(II) atoms exist in a linear coordination geometry [C-Hg-C = 178.9 (2) and 180 degrees ] formed by two carbene C atoms from the imidazole rings. In the crystal, the cations and anions are connected via C-H?F hydrogen bonds, forming a three-dimensional network. PMID- 22064755 TI - Diphenyl [(S)-1-phenylpropanamido]-phosphate. AB - The title compound, C(21)H(22)NO(3)P, was synthesized from the reaction of (C(6)H(5)O)(2)P(O)(Cl) and S-1-phenyl-propyl-amine (1:2 mole ratio) at 273 K, followed by removal of the S-1-phenyl-propyl-amine hydro-chloride by-product by dissolving in H(2)O. The P atom is located in a distorted tetra-hedral environment. The bond angles at the P atom vary from 99.51 (12) to 116.68 (12) degrees . The sp(2) character of the N atom is reflected by the C-N-P angle [120.9 (2) degrees ]. The P=O group and the N-H unit adopt an anti orientation with respect to one another. In the crystal, adjacent mol-ecules are linked via N H?O(P) hydrogen bonds into a one-dimensional arrangement running parallel to the a axis. PMID- 22064756 TI - 2,5-Bis(pyridinium-2-yl)-3,6-bis-(2-pyrid-yl)pyrazine bis-[tetra-chlorido aurate(III)]. AB - In the title compound, (C(24)H(18)N(6))[AuCl(4)](2), the cation is located on an inversion center. Each of the two independent Au(III) ions lies on an inversion center and has a distorted square-planar geometry. In the crystal, inter molecular C-H?Cl hydrogen bonds, pi-pi inter-actions [centroid-centroid distances = 3.5548 (16) and 3.7507 (16) A] and Au?pi inter-actions [Au?centroid distance = 3.6424 (10) A] are effective in the stabilization of the structure, resulting in the formation of a supra-molecular structure. Intra-molecular N-H?N hydrogen bonds are present in the cation. PMID- 22064757 TI - Correlation between psychopathology and urinary steroid and biogenic amine metabolites in male schizophrenics. AB - In eight normals, eight anxiety neurotics and eight patients of acute schizophrenic episode, twenty-four-hour urinary excretion of each of the following was measured: (1) 17-ketosteroids (17-KS)-total, glucuronides) and sulphates, (2)17-hydroxycorticosteroids 17-KS)-total, conjugated and free, (3) Vanilamendelic acid (VMA), and (4) total indoles. In case of schizophrenics, such measurements were made before starting treatment, and after 30 days of chlorpromazine therapy. The psychopathology of schizophrenic subjects were rated on Rockland and Pollir (R. P.) scale on both occasions. Correlating the psychopathology with the biochemical values, amongst schizophrenics, R. P. score was found to show significant positive correlation with VMA and, to a lesser extent with total indoles. Schizophrenics excrated greater amount of VMA than normals and this returned to near normal levels with treatment. On the other hand, schizophrenics excreted lower amounts of most steroid fractions than normals, but amongst schizophrenics, there was no significant correlation between R. P. score arid steroid excretion. PMID- 22064758 TI - Triethyl-ammonium 2,4,6-trisulfanylidene-1,3,5-triazinan-1-ide. AB - The asymmetric unit of the title compound, C(6)H(16)N(+).C(3)H(2)N(3)S(3) (-), contains two independent ion pairs. The 2,4,6-trithioxo-1,3,5-triazinan-1-ide anion features an almost planar six-membered ring (r.m.s. deviations = 0.009 and 0.018 A) having exocyclic double-bond S atoms. The anions inter-act by N-H?S hydrogen bonds to generate a chain running along [110]. The triethyl-ammonium cations are hydrogen bonded to the anions with the ammonium H atom forming a hydrogen bond to the negatively-charged N atom of the anion. In the crystal structure, both triethyl-ammonium cations are disordered over two orientations with equal occupancies. PMID- 22064759 TI - 3,15-Dimeth-oxy-10-methyl-tricyclo-[9.4.0.0]penta-deca-1(11),2(7),3,5,9,12,14 heptaen-8-one. AB - The title mol-ecule, C(18)H(16)O(3), contains three fused rings, of which the seven-membered cyclo-hept-2-enone ring has a screw-boat conformation. The two meth-oxy-phenyl rings make a dihedral angle of 50.4 (2) degrees . In the crystal, mol-ecules are linked by inter-molecular C-H?O hydrogen bonds, leading to a three dimensional supra-molecular architecture. PMID- 22064760 TI - Recurrent pregnancy loss: TNF-alpha and IL-10 polymorphisms. AB - BACKGROUND: The recurrent pregnancy loss requires careful consideration of genetic, anatomic, endocrine, infectious and immunological factors. Cytokine gene polymorphisms in the promoter regions of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 are associated with recurrent pregnancy loss. AIM: The aim of present study was to investigate the association of the IL-10 -592C/A and TNF alpha-308 G/A, promoter polymorphisms among women with at least three consecutive miscarriages. MATERIALS AND METHODS: Genotyping was done in 50 women with RPL for IL-10-592C/A and TNF-alpha-308G/A promoter polymorphism to see the association of these loci with pregnancy loss. The control group included 50 healthy women having two or more children (mean age of the female subjects 35 years) for statistical comparisons. RESULTS: IL- 10-592C/A and TNF-alpha-308G/A promoter polymorphisms were not associated with the recurrent miscarriages. CONCLUSIONS: There is a need to screen a larger sample and in different ethnic groups using IL 10-592C/A and TNF-alpha-308G/A markers to understand their association with recurrent miscarriages. This would further help in efficient management of immunologically mediated recurrent miscarriages at the sample/individual level. PMID- 22064761 TI - Juvenile general paralysis of insane: a case report. PMID- 22064763 TI - catena-Poly[[[tetra-aqua-nickel(II)]-MU-4,4'-bipyridyl-kappaN:N'] 3,3'-(p-phenyl ene)diacrylate]. AB - In the title compound, {[Ni(C(10)H(8)N(2))(H(2)O)(4)](C(12)H(8)O(4))}(n), the Ni(II), 4,4'-bipyridyl (bipy) and 3,3'-(p-phenyl-ene)diacrylate (L(2-)) moieties are situated on inversion centres. The bipy ligands bridge Ni(II) ions into positively charged polymeric chains along [101]. The Ni(II) atom is coordinated by two N atoms from two bipy ligands and four water mol-ecules in a distorted octa-hedral geometry. L(2-) anions inter-act with the polymeric chains via O-H?O hydrogen bonds, forming a three-dimensional supra-molecular network. PMID- 22064764 TI - cis-Aqua-bis-(2,2'-bipyrimidine-kappaN,N)iodidomanganese(II) iodide monohydrate. AB - The asymmetric unit of the title compound, [MnI(C(8)H(6)N(4))(2)(H(2)O)]I.H(2)O, consists of a cationic Mn(II) complex, an I(-) anion and a solvent water mol ecule. In the complex, the Mn(II) ion is six-coordinated in a distorted octa hedral environment defined by four N atoms of the two chelating 2,2'-bipyrimidine (bpym) ligands, one I(-) anion and one O atom of a water ligand. The dihedral angle between the least-squares planes of the two bpym ligands [maximum deviation = 0.092 (7) A] is 79.9 (1) degrees . In the crystal, the complex, anion and solvent water mol-ecule are linked by inter-molecular O-H?O, O-H?I and O-H?N hydrogen bonds. PMID- 22064765 TI - Bilateral osseous stenosis of the internal auditory canal: case report. AB - Osteomas as well as exostoses of the internal auditory canal are rare, benign, usually slow-growing lesions. The most common localizations of these temporal bone lesions are the mastoid cortex and the external auditory canal. A rare case is reported of bilateral osseous stenosis of the internal auditory canal, in the absence of clinical (auditory, vestibular and facial nerve) symptoms. In the absence of auditory, vestibular and/or facial nerve symptoms, long-term follow-up should be assessed; surgical intervention may be warranted only if symptoms are present. PMID- 22064766 TI - Use of the MEGA exposure database for the validation of the Stoffenmanager model. AB - OBJECTIVES: This paper explores the usefulness of the exposure database MEGA for model validation and evaluates the capability of two Stoffenmanager model equations (i.e. handling of powders/granules and machining) to estimate workers exposure to inhalable dust. METHODS: For the task groups, 'handling of powders and granules' (handling) and 'machining of wood and stone' (machining) measurements were selected from MEGA and grouped in scenarios depending on task, product, and control measures. The predictive capability of the model was tested by calculating the relative bias of the single measurements and the correlation between geometric means (GMs) for scenarios. The conservatism of the model was evaluated by checking if the percentage of measurement values above the 90th percentile estimate was <=10%. RESULTS: From 22 596 personal measurements on inhalable dust within MEGA, 390 could be selected for handling and 1133 for machining. The relative bias for the task groups was -25 and 68%, respectively, the percentage of measurements with a higher result than the estimated 90th percentile 11 and 7%. Correlations on a scenario level were good for both model equations as well for the GM (handling: r(s) = 0.90, n = 15 scenarios; machining: r(s) = 0.84, n = 22 scenarios) as for the 90th percentile (handling: r(s) = 0.79; machining: r(s) = 0.76). CONCLUSIONS: The MEGA database could be used for model validation, although the presented analyses have learned that improvements in the database are necessary for modelling purposes in the future. For a substantial amount of data, contextual information on exposure determinants in addition to basic core information is stored in this database. The relative low bias, the good correlation, and the level of conservatism of the tested model show that the Stoffenmanager can be regarded as a useful Tier 1 model for the Registration, Evaluation, Authorisation and Restriction of Chemicals legislation. PMID- 22064767 TI - 8-Hy-droxy-2-methyl-quinolinium diiodido(2-methyl-quinolin-8-olato kappaN,O)zincate. AB - The reaction of 2-methyl-8-hy-droxy-quinoline and zinc iodide in acetonitrile affords the title salt, (C(10)H(10)NO)[Zn(C(10)H(8)NO)I(2)], in which the Zn(II) ion is coordinated by a N,O-chelating 2-methyl-quinolin-8-olate ligand and two iodide ligands in a distorted tetra-hedral geometry. The cation is linked to the anion by an O-H?O hydrogen bond. PMID- 22064768 TI - 4-[Bis(4-fluorophenyl)methyl]piperazin-1-ium 2-(2-phenylethyl)benzoate. AB - The asymmetric unit of the title salt, C(17)H(19)F(2)N(2) (+.)C(15)H(13)O(2) (-), derived from a 1,4-diaza-cyclo-hexane derivative and a carb-oxy-lic acid, contains two formula units. The cation is protonated at the secondary amine functionality. The six-membered heterocycles adopt chair conformations. The fluorophenyl rings in the two cations make dihedral angles of 77.21 (19) and 78.8 (2) degrees while the aromatic rings in the anions enclose angles of 69.5 (2) and 69.9 (2) degrees . In the crystal, classical N-H?O hydrogen bonds as well as C-H?F and C-H?O contacts connect the entities into layers parallel to ac. PMID- 22064769 TI - Tris(1,10-phenanthroline-5,6-dione-kappaN,N')zinc bis-(perchlorate) acetonitrile monosolvate. AB - In the title compound, [Zn(C(12)H(6)N(2)O(2))(3)](ClO(4))(2).CH(3)CN, the Zn(II) atom is coordinated by six N atoms from three chelating 1,10-phenanthroline-5,6 dione ligands in a distorted octa-hedral environment. In the crystal, inter molecular C-H?O hydrogen bonds and O?pi and N?pi inter-actions [O?centroid distances = 2.907 (5) and 2.843 (7) A; N?centroid distance = 2.861 (10) A] link the complex cations, perchlorate anions and acetonitrile solvent mol-ecules into a three-dimensional network. PMID- 22064770 TI - 2-Amino-4,6-dimeth-oxy-pyrimidin-1-ium p-toluene-sulfonate. AB - In the title salt, C(6)H(10)N(3)O(2) (+).C(7)H(7)O(3)S(-), the 2-amino-4,6-dimeth oxy-pyrimidinium cation inter-acts with the sulfonate group of the p-toluene sulfonate anion via a pair of N-H?O hydrogen bonds, forming a cyclic hydrogen bonded R(2) (2)(8) motif, which in the crystal is linked by further intemolecular N-H?O hydrogen bonds, forming supra-molecular chains along the c axis. Furthermore, neighboring chains are inter-linked via weak C-H?O hydrogen bonds and C-H?pi inter-actions, forming layers. PMID- 22064771 TI - 3-Methyl-5-phen-oxy-1-phenyl-1H-pyrazole-4-carbaldehyde. AB - In the title compound, C(17)H(14)N(2)O(2), the pyrazole ring makes dihedral angles of 73.67 (4) and 45.99 (4) degrees , respectively, with the adjacent phenyl and phen-oxy rings. In the crystal, there are no classical hydrogen bonds, but a weak C-H?pi inter-action is observed. PMID- 22064772 TI - 2,4-Dichloro-N-(2,6-dimethyl-phen-yl)benzene-sulfonamide. AB - In the crystal of the title compound, C(14)H(13)Cl(2)NO(2)S, the N-H bond in the C-SO(2)-NH-C segment orients itself away from the two ortho-methyl groups in the aniline benzene ring and towards the ortho-chloro group of the sulfonyl benzene ring. The mol-ecule is bent at the S atom with a C-SO(2)-NH-C torsion angle of 100.48 (18) degrees . The sulfonyl and aniline benzene rings are tilted relative to each other by 69.6 (1) degrees . Inter-molecular N-H?O hydrogen bonds link the mol-ecules into infinite chains. PMID- 22064773 TI - (Z)-2-Sulfanyl-idene-5-(thio-phen-2-yl-methyl-idene)imidazolidin-4-one. AB - The mol-ecule of the title compound, C(8)H(6)N(2)OS(2), has a V shape with two five-membered rings attached to a methyl-ene C atom. All non-H atoms are approximately coplanar (r.m.s. deviation = 0.096 A). In the crystal, mol-ecules are linked by N-H?O hydrogen bonds into layers. The thio-phene ring is disordered over two positions; the major orientation has an occupancy of 0.683 (3). is there an intramolecular N---H...S bond? PMID- 22064774 TI - Acridine 0.75-hydrate. AB - The title compound, C(13)H(9)N.0.75H(2)O was obtained during a study of the polymorphic system of acridine, by slow evaporation from an ethanol-water solution. There are two acridine mol-ecules (indicated by I and II, respectively) and one and a half water mol-ecules in the asymmetric unit. The half-mol-ecule of water is located on a crystallographic twofold axis. The crystal structure is built up from two threads of mol-ecule II sewn together with water mol-ecules through O-H?O and O-H?N hydrogen bonds from one side and with pi-pi inter-actions [centroid-centroid distance = 3.640 (3) and 3.7431 (3) A] between overlapping mol ecules II on the other side. Mol-ecule I is attached to this thread from both sides by C-H?O hydrogen bonds. The threads are connected to each other by pi-pi inter-actions [centroid-centroid distances = 3.582 (3) and 3.582 (3) A] between the inner side of mol-ecule I and stabilized by a C-H?pi inter-action on the other side of mol-ecule I. This thread with rows of mol-ecule I hanging on its sides is generated by translation perpendicular to the a axis. PMID- 22064775 TI - Standardisation of gujrati version of middlesex hospital questionnaire. AB - The Middlesex Hospital Questionnaire is a short clinical diagnostic self rating scale for psychoneurotic patients constructed by Crown and Crisp (1966). Aim of the present study was to prepare Gujarati Version of the M.H.Q. and to establish the reliability and validity of the same.Gujarati version of the M.H.Q. was given to 204 normal population consisting of university students, school teachers, factory workers, house wives and middle aged men from different walks of the life to test the validity. The test was also administered to 30 neurotic patients. This Gujarati version was found to be reliable. There was highly significant difference between normal population and neurotic patients on total score and on all the six subtests, thus establishing the validity of the Gujarati version. It also related well with the clinical diagnosis in most of the cases. PMID- 22064776 TI - 3,4-Dibromo-2,5-bis-[(dieth-oxy-phosphor-yl)meth-yl]-1-phenyl-sulfonyl-1H pyrrole. AB - In the title compound, C(20)H(29)Br(2)NO(8)P(2)S, the pyrrole ring is essentially planar, with a maximum deviation of 0.013 (3) A for a C atom. The pyrrole ring is almost orthogonal to the sulfonyl-bound phenyl ring, with a dihedral angle 88.5 (2) degrees . Both P atoms exhibit distorted tetra-hedral configurations with O-P O angles widened and O-P-C angles narrowed from the ideal tetra-hedral value. In the crystal, mol-ecules are linked into centrosymmetric dimers via C-H?O inter actions, resulting in R(2) (2)(10) graph-set motifs which are further consolidated by R(2) (2)(13) graph-set ring motifs via C-H?O inter-actions, further resulting in chains of mol-ecules running parallel to the c axis; a phosphono O atom is involved in bifurcated hydrogen bonding. All the eth-oxy groups are disordered over two positions each with unequal site-occupancy factors. PMID- 22064777 TI - Ethyl 1-phenyl-sulfonyl-1H-indole-2-carboxyl-ate. AB - In the title compound, C(17)H(15)NO(4)S, the six-membered ring of the indole unit makes a dihedral angle of 72.40 (5) degrees with the phenyl ring. The mol-ecular structure features a short C-H?O contact. PMID- 22064778 TI - Efficacy of propranolol on schizophrenic thought disorder. AB - 15 schizophrenic patients were treated with dl-propranolol in a 4 week open study. Dosage was gradually increased over a period of 17 days to 1920 mg/day. Improvements were rated on Thought Disorder Scores (A & B) of the MBPRS and GPRS subscale for schizophrenia. Majority of the patients showed a 50% improvement in terms of their residual scores by the 4th week of treatment and the side effects experienced were minimal. PMID- 22064780 TI - N'-[(E)-2-Hy-droxy-3,5-diiodo-benzyl-idene]cyclo-hexa-ne-1-carbohydrazide. AB - In the title compound, C(14)H(10)I(2)N(2)O(2), the two aromatic rings are inclined at a dihedral angle of 16.72 (33) degrees . The mol-ecular structure is stabilized by an intra-molecular O-H?N hydrogen bond. In the crystal, inter molecular N-H?O inter-actions link the mol-ecules into chains running along the c axis. C-H?O inter-actions also occur. The crystal used for the structure determination was a non-merohedral twin with a domain ratio of 0.972 (2):0.028 (2). PMID- 22064781 TI - Outcomes of structural fat grafting for paralytic and non-paralytic dysphonia. AB - Aims of this prospective study were to evaluate the results of vocal fold structural fat grafting for glottic insufficiency and to compare the outcomes obtained in unilateral vocal fold paralysis (UVFP) and congenital or acquired soft tissue defects in vocal folds. Sixty-six consecutive patients with breathy dysphonia, in 43 cases (aged 16-79 years) related to UVFP and in 23 cases (aged 16-67 years) related to vocal fold iatrogenic scar or sulcus vocalis, underwent autologous structural fat grafting into vocal folds. Lipoaspirates were centrifuged at 1200 g for 3 min to separate and remove blood, cell debris and the oily layer. The refined fat was injected under direct microlaryngoscopy in a multilayered way. The main outcome measures were grade, roughness, breathiness, asthenicity and strain (GRBAS) perceptual evaluation, maximum phonation time (MPT), self-assessed Voice Handicap Index (VHI), and voice acoustic analysis, considered pre-operatively and at 3 and 6 months after fat grafting. After surgery, MPT, VHI, G and B improved in both groups (p < 0.05). In particular, G and VHI functional subscales showed a significantly greater decrease in patients with UVFP (p < 0.05). The acoustic variables improved significantly only in the UVFP group (p < 0.005). From 3 to 6 months postoperatively, most variables showed a trend with further improvement. Vocal fold structural fat grafting was significantly effective in treating glottic insufficiency due to UVFP or soft tissue defects. Perceptual, acoustic and subjective assessments confirmed that patients with UVFP had better outcomes than those with soft tissue defects. PMID- 22064782 TI - N-(2-Bromo-phen-yl)-4-methyl-N-(4-methyl-phen-ylsulfon-yl)benzene-sulfonamide. AB - In the title compound, C(20)H(18)BrNO(4)S(2), the mean planes formed by the toluene substituents are inclined at a dihedral angle of 45.34 (8) degrees . The bromo-benzene group is disordered over two positions with an occupancy ratio of 0.74:0.26, resulting in two conformations of the ring; the two rings are oriented at a dihedral angle of 6.6 (6) degrees with each other. In the crystal structure, weak C-H?O inter-actions connect the mol-ecules in a zigzag manner along the a axis. PMID- 22064783 TI - Tetra-kis(MU(2)-2-phen-oxy-propionato)-kappaO,O':O';kappaO:O,O';kappaO:O'-bis [(1,10-phenanthroline-kappaN,N')(2-phen-oxy-propionato-kappaO,O')cerium(III)]. AB - In the centrosymmetric binuclear title complex, [Ce(2)(C(9)H(9)O(3))(6)(C(12)H(8)N(2))(2)], the two Ce(III) ions are linked by four 2-phen-oxy-propionate groups in bi- and tridentate bridging modes. Each Ce(III) ion is nine-coordinated by one 1,10-phenanthroline mol-ecule, two O atoms from a chelating carboxyl-ate, two O atoms derived from a MU(3)-carboxylate and two O atoms derived from two MU(2)-carboxylate ligands in a distorted CeN(2)O(7) monocapped square-anti-prismatic geometry. PMID- 22064784 TI - Bis(nitrato-kappaO)tetra-kis-[1-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-1 one]copper(II). AB - In the title complex, [Cu(NO(3))(2)(C(11)H(11)N(3)O)(4)], the Cu(II) atom is situated on a centre of inversion and is coordinated by two O atoms from two nitrate anions and four N atoms from four monodentate 1-phenyl-3-(1H-1,2,4 triazol-1-yl)propan-1-one ligands in a distorted octa-hedral geometry. Weak inter molecular C-H?O and C-H?N hydrogen bonds result in a supra-molecular layer parallel to (101). These layers are connected by pi-pi inter-actions between the benzene rings [centroid-centroid distance = 3.891 (2) A]. PMID- 22064785 TI - 3-(4-Bromo-anilino)-3-(4-chloro-phen-yl)-1-phenyl-propan-1-one. AB - The asymmetric C atom in the title compound, C(21)H(17)BrClNO, is in a slightly distorted tetra-hedral environment and the NH unit adopts a gauche orientation with respect to the CO group. In the crystal, pairs of inter-molecular N-H?O hydrogen bonds form centrosymmetric dimers. PMID- 22064786 TI - N,N'-Bis(2,5-dichloro-phen-yl)isophthalamide. AB - The asymmetric unit of the title compound, C(20)H(12)Cl(4)N(2)O(2), contains one half-mol-ecule with a center of symmetry along a C?C axis of the central benzene ring. The two C=O groups adopt an anti orientation and the two amide groups are twisted away from the central benzene ring by 27.38 (3) and 27.62 (4) degrees . The mean planes of the dichloro-substituted benzene rings are twisted by 7.95 (4) degrees with respect to the benzene ring. The crystal packing is stabilized by weak inter-molecular N-H?O inter-actions. PMID- 22064787 TI - Primary abdominal pregnancy following intra-uterine insemination. AB - Primary abdominal pregnancy is an extremely rare type of extrauterine pregnancy. It has been reported from many unusual intra-abdominal sites. We report a case of primary abdominal pregnancy following intra-uterine insemination (not reported earlier to our knowledge). Implanted on the anterior surface of the uterus possibly related to an endometriotic foci. Early diagnosis enabled laparoscopic management of this case. PMID- 22064788 TI - Potassium ditin(IV) tris-[phosphate(V)], KSn(2)(PO(4))(3). AB - The title compound, KSn(2)(PO(4))(3), belongs to the NASICON-type family of phosphates with the space group R[Formula: see text]. Its structure is constructed by very regular [with P-O distances ranging from 1.513 (6) to 1.522 (6) A] PO(4) tetra-hedra and SnO(6) octa-hedra on the 3. axis, which are linked by O atoms, forming an [Sn(2)(PO(4))(3)] framework. The K atoms occupy the [Formula: see text]. axis sites and are located in the voids of this arrangement. The crystal studied was a merohedral twin with twin law (010 100 00[Formula: see text]) and a component ratio of 0.580 (7):0.420 (7). PMID- 22064789 TI - 4-Benz-yloxy-2-bromo-1-meth-oxy-benzene. AB - In the title compound, C(14)H(13)BrO(2), the phenyl ring is oriented at a dihedral angle of 72.6 (3) degrees with respect to the bromo-meth-oxy-phenyl ring. The crystal structure is stabilized by weak inter-molecular C-H?O inter actions. PMID- 22064790 TI - A new mixed group 5 metal selenide, Nb(1.41)V(0.59)Se(9). AB - The new mixed-metallic phase, niobium vanadium nona-selenide, (Nb(2-x)V(x))Se(9) (0.18<= x <= 0.59) is isostructural with monoclinic V(2)Se(9). The structure is composed of chains of bicapped trigonal-prismatic [MSe(8)] units. The metal (M) site is occupied by statistically disordered Nb [0.706 (5)] and V [0.294 (5)] atoms. Two trigonal prisms are linked by sharing a recta-ngular face composed of two Se(2) (2-) pairs. Through three edging and capping Se atoms, the chains are extended along [101]. The chain shows alternating short [2.8847 (7) A] and long [3.7159 (7) A] M-M distances. The structure shows a wide range of Se-Se inter actions. In addition to the Se(2) (2-) pairs of the recta-ngular face, an inter mediate Se?Se separation [2.6584 (5) A] is found. The amount of each metal can vary, [(Nb(2-x)V(x))Se(9), 0.18 <= x <=m 0.59] and they seem to form a random substitutional solid solution. The M-M distances increase gradually by increasing the amount of Nb atoms. The classical charge-balance of the compound can be described as [M(4+)](2)[Se(2) (2-)](2)[Se(5) (4-)]. PMID- 22064791 TI - 2-(2-p-Tolyl-benzo[g]quinolin-3-yl)ethanol. AB - In the title compound, C(22)H(19)NO, the pyridine ring and the adjacent naphthalene ring system are nearly coplanar, making a dihedral angle of 3.3 (1) degrees , while the pyridine and benzene rings are perpendicular to each other, with a dihedral angle of 89.9 (1) degrees . The crystal packing is stabilized by inter-molecular O-H?N hydrogen bonds and C-H?pi inter-actions. PMID- 22064792 TI - Poly[(MU(6)-6-oxidopyridinium-2-carboxyl-ato)caesium]. AB - The asymmetric unit of the polymeric title salt, [Cs(C(6)H(4)NO(3))](n), comprises a Cs(+) cation and a 6-oxidopyridinium-2-carboxyl-ate anion. The Cs(+) cation is six-coordinated by O atoms derived from two oxido and four carboxyl-ate O atoms; each O atom in the anion bridges two Cs(+) cations. In the crystal, inter-molecular N-H?O hydrogen bonding is present and contributes to the stability of the three-dimensional network generated by the bridging O atoms. PMID- 22064793 TI - Aqua-(2,9-dimethyl-1,10-phenanthroline-kappaN,N')diformato-kappaO,O';kappaO nickel(II) monohydrate. AB - The asymmetric unit of the title compound, [Ni(HCO(2))(2)(C(14)H(12)N(2))(H(2)O)].H(2)O, contains a mononuclear complex mol ecule hydrogen bonded to a lattice water mol-ecule. The Ni(II) atom exhibits a distorted octa-hedral coordination geometry formed by the N atoms from a 2,9 dimethyl-1,10-phenanthroline ligand, two O atoms of a chelating formate anion, one aqua O atom and one O atom of a coordinating formate anion. The mol-ecules are assembled into chains extending along [100] through by O-H?O hydrogen bonds. The supra-molecular chains are further linked into layers parallel to (011) by weak pi-pi packing inter-actions [centroid-centroid separation = 3.768 (2) A]. The resulting layers are stacked to meet the requirement of close-packing patterns. PMID- 22064794 TI - Capillary haemangioma of the middle ear: a rare lesion difficult to evaluate. AB - Haemangiomas are benign vascular tumours relatively common in the head and neck district but very rare in the temporal bone. Depending on its clinical presentation, haemangioma can be mistaken for other vascular masses such as glomus tumour or other lesions of the middle ear. Unfortunately, clinical and radiological evaluation may be insufficient to make a pre-operative diagnosis and the diagnosis is often based upon intra-operative biopsy specimen findings. PMID- 22064795 TI - Trichlorido-1kappaCl,2kappaCl-(2,6-dimethyl-phenolato-2kappaO)-MU-oxido bis{1,2(eta)-2,3,4,5-tetra-methyl-1-[4-(trimethyl-silyl)phen-yl]cyclo-penta-dien yl}dititanium(IV). AB - The title dinuclear titanocene, [Ti(2)(C(8)H(9)O)(C(18)H(25)Si)(2)Cl(3)O], contains one Ti atom tetra-hedrally coordinated by two Cl atoms, a bridging O atom and the substituted cyclo-penta-dienyl ligand, and another Ti atom tetra hedrally coordinated by a Cl atom, a bridging O atom, the 2,6-dimethyl-phenolate ligand and the substituted cyclo-penta-dienyl ligand. The bridging O atom lies on a twofold rotation axis. PMID- 22064796 TI - Kernelized locality-sensitive hashing. AB - Fast retrieval methods are critical for many large-scale and data-driven vision applications. Recent work has explored ways to embed high-dimensional features or complex distance functions into a low-dimensional Hamming space where items can be efficiently searched. However, existing methods do not apply for high dimensional kernelized data when the underlying feature embedding for the kernel is unknown. We show how to generalize locality-sensitive hashing to accommodate arbitrary kernel functions, making it possible to preserve the algorithm's sublinear time similarity search guarantees for a wide class of useful similarity functions. Since a number of successful image-based kernels have unknown or incomputable embeddings, this is especially valuable for image retrieval tasks. We validate our technique on several data sets, and show that it enables accurate and fast performance for several vision problems, including example-based object classification, local feature matching, and content-based retrieval. PMID- 22064797 TI - Constrained Nonnegative Matrix Factorization for Image Representation. AB - Nonnegative matrix factorization (NMF) is a popular technique for finding parts based, linear representations of nonnegative data. It has been successfully applied in a wide range of applications such as pattern recognition, information retrieval, and computer vision. However, NMF is essentially an unsupervised method and cannot make use of label information. In this paper, we propose a novel semi-supervised matrix decomposition method, called Constrained Nonnegative Matrix Factorization (CNMF), which incorporates the label information as additional constraints. Specifically, we show how explicitly combining label information improves the discriminating power of the resulting matrix decomposition. We explore the proposed CNMF method with two cost function formulations and provide the corresponding update solutions for the optimization problems. Empirical experiments demonstrate the effectiveness of our novel algorithm in comparison to the state-of-the-art approaches through a set of evaluations based on real-world applications. PMID- 22064798 TI - Latent log-linear models for handwritten digit classification. AB - We present latent log-linear models, an extension of log-linear models incorporating latent variables, and we propose two applications thereof: log linear mixture models and image deformation-aware log-linear models. The resulting models are fully discriminative, can be trained efficiently, and the model complexity can be controlled. Log-linear mixture models offer additional flexibility within the log-linear modeling framework. Unlike previous approaches, the image deformation-aware model directly considers image deformations and allows for a discriminative training of the deformation parameters. Both are trained using alternating optimization. For certain variants, convergence to a stationary point is guaranteed and, in practice, even variants without this guarantee converge and find models that perform well. We tune the methods on the USPS data set and evaluate on the MNIST data set, demonstrating the generalization capabilities of our proposed models. Our models, although using significantly fewer parameters, are able to obtain competitive results with models proposed in the literature. PMID- 22064799 TI - Object recognition by discriminative combinations of line segments, ellipses, and appearance features. AB - We present a novel contour-based approach that recognizes object classes in real world scenes using simple and generic shape primitives of line segments and ellipses. Compared to commonly used contour fragment features, these primitives support more efficient representation since their storage requirements are independent of object size. Additionally, these primitives are readily described by their geometrical properties and hence afford very efficient feature comparison. We pair these primitives as shape-tokens and learn discriminative combinations of shape-tokens. Here, we allow each combination to have a variable number of shape-tokens. This, coupled with the generic nature of primitives, enables a variety of class-specific shape structures to be learned. Building on the contour-based method, we propose a new hybrid recognition method that combines shape and appearance features. Each discriminative combination can vary in the number and the types of features, where these two degrees of variability empower the hybrid method with even more flexibility and discriminative potential. We evaluate our methods across a large number of challenging classes, and obtain very competitive results against other methods. These results show the proposed shape primitives are indeed sufficiently powerful to recognize object classes in complex real-world scenes. PMID- 22064800 TI - Simultaneously fitting and segmenting multiple-structure data with outliers. AB - We propose a robust fitting framework, called Adaptive Kernel-Scale Weighted Hypotheses (AKSWH), to segment multiple-structure data even in the presence of a large number of outliers. Our framework contains a novel scale estimator called Iterative Kth Ordered Scale Estimator (IKOSE). IKOSE can accurately estimate the scale of inliers for heavily corrupted multiple-structure data and is of interest by itself since it can be used in other robust estimators. In addition to IKOSE, our framework includes several original elements based on the weighting, clustering, and fusing of hypotheses. AKSWH can provide accurate estimates of the number of model instances and the parameters and the scale of each model instance simultaneously. We demonstrate good performance in practical applications such as line fitting, circle fitting, range image segmentation, homography estimation, and two--view-based motion segmentation, using both synthetic data and real images. PMID- 22064801 TI - Spacetime texture representation and recognition based on a spatiotemporal orientation analysis. AB - This paper is concerned with the representation and recognition of the observed dynamics (i.e., excluding purely spatial appearance cues) of spacetime texture based on a spatiotemporal orientation analysis. The term "spacetime texture" is taken to refer to patterns in visual spacetime, (x,y,t), that primarily are characterized by the aggregate dynamic properties of elements or local measurements accumulated over a region of spatiotemporal support, rather than in terms of the dynamics of individual constituents. Examples include image sequences of natural processes that exhibit stochastic dynamics (e.g., fire, water, and windblown vegetation) as well as images of simpler dynamics when analyzed in terms of aggregate region properties (e.g., uniform motion of elements in imagery, such as pedestrians and vehicular traffic). Spacetime texture representation and recognition is important as it provides an early means of capturing the structure of an ensuing image stream in a meaningful fashion. Toward such ends, a novel approach to spacetime texture representation and an associated recognition method are described based on distributions (histograms) of spacetime orientation structure. Empirical evaluation on both standard and original image data sets shows the promise of the approach, including significant improvement over alternative state-of-the-art approaches in recognizing the same pattern from different viewpoints. PMID- 22064802 TI - 6-Hy-droxy-2H-1,3-benzodioxole-5-carbaldehyde. AB - The title compound, C(8)H(6)O(4), crystallizes with two independent mol-ecules in the asymmetric unit. The benzodioxole ring system is almost planar in each mol ecule, with maximum deviations of 0.008 (1) and 0.007 (1) A. The mol-ecular structure is characterized by strong electrostatic intra-molecular O?O contacts [2.649 (3) A] and intra-molecular O-H?O hydrogen-bonding inter-actions. Inter molecular O?O inter-actions [3.001 (2) A] are observed in the crystal structure. PMID- 22064803 TI - N,N'-Bis(2-methyl-phen-yl)-N''-(2,2,2-trichloro-acet-yl)phospho-ric triamide. AB - In the title compound, C(16)H(17)Cl(3)N(3)O(2)P, the P-N bonds in the P(O)[NH(2 CH(3))C(6)H(4)](2) unit [1.623 (4) and 1.637 (3) A] are shorter than the P-N bond in the C(O)NHP(O) fragment [1.704 (3) A]. The phosphoryl and carbonyl groups are anti with respect to each other and the P atom has a distorted tetra-hedral configuration. In the crystal, adjacent mol-ecules are linked via N-H?O(P) and N H?O(C) hydrogen bonds into an extended chain parallel to [101]. PMID- 22064804 TI - 2-(4-Chloro-phen-yl)-3,5-dimethyl-1lambda,2-thia-zine-1,1-dione. AB - In the title compound, C(12)H(12)ClNO(2)S, the S atom is displaced by 0.708 (2) A out of the plane through the remaining atoms of the thia-zine ring (r.m.s. deviation = 0.0823 A). This plane makes a dihedral angle of 89.33 (7) degrees with the phenyl ring. In the crystal, adjacent mol-ecules are connected through C H?O hydrogen bonds into layers parallel to the bc plane. PMID- 22064805 TI - Tetra-kis(MU(2)-2-phen-oxy-propionato)-kappaO,O':O';kappaO:O,O';kappaO:O'-bis [(1,10-phenanthroline-kappaN,N')(2-phen-oxy-propionato kappaO,O')gadolinium(III)]. AB - In the centrosymmetric binuclear title complex, [Gd(2)(C(9)H(9)O(3))(6)(C(12)H(8)N(2))(2)], the two Gd(III) ions are linked by four 2-phen-oxy-propionate (L) groups in bi- and tridentate bridging modes. Each Gd(III) ion is nine-coordinated by one 1,10-phenanthroline mol-ecule, one bidentate chelating carboxyl-ate group and four bridging carboxyl-ate groups in a distorted GdN(2)O(7) monocapped square-anti-prismatic geometry. PMID- 22064806 TI - N,N'-(Ethane-1,2-di-yl)dibenzene-sulfonamide. AB - In the title compound, C(14)H(16)N(2)O(4)S(2), the dihedral angle between the terminal phenyl rings is 77.07 (13) degrees . The geometries around the S atoms are distorted tetra-hedral, with O-S-O angles of 120.66 (12) and 119.44 (11) degrees . In the crystal, mol-ecules are stacked in columns along the a axis via inter-molecular N-H?O and C-H?O hydrogen bonds. PMID- 22064807 TI - A comparative study of guilt and hostility in depressive subjects. PMID- 22064808 TI - 8-Hy-droxy-2-methyl-quinolinium tetra-chlorido(pyrazine-2-carboxyl-ato kappaN,O)stannate(IV) methanol monosolvate. AB - In the title solvated salt, (C(10)H(10)NO)[SnCl(4)(C(5)H(3)N(2)O(2))].CH(3)OH, the Sn(IV) atom is chelated by the N,O-bidentate pyrazine-2-carboxyl-ate ligand and four chloride ions, and shows a distorted octa-hedral SnNOCl(4) coordination at the metal atom. The 8-hy-droxy-2-methyl-quinolinium cation and the anion are linked to the methanol mol-ecules by O-H?O, O-H?N and N-H?O hydrogen bonds, generating a linear chain running along [1[Formula: see text]0]. There are two independent ion pairs and solvent mol-ecules in the asymmetric unit. The crystal studied was a non-merohedral twin with a 41.8 (1)% twin component. PMID- 22064809 TI - rac-3-{4-[(Furan-2-ylmethyl-idene)-amino]-3-methyl-5-sulfanyl-idene-4,5-dihydro 1H-1,2,4-triazol-1-yl}-1,3-diphenyl-propan-1-one. AB - In the title mol-ecule, C(23)H(20)N(4)O(2)S, the triazole ring forms dihedral angles of 150.3 (2), 77.3 (2) and 77.6 (2) degrees , respectively, with the furan ring and the phenyl rings. The furan ring is almost perpendicular to the central phenyl ring, making a dihedral angle of 86.0 (3) degrees . PMID- 22064810 TI - 4-(5-Oxo-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzene-sulfonamide. AB - With respect to the aliphatic planar five-membered ring (r.m.s. deviation = 0.011 A) of the title compound, C(15)H(13)N(3)O(2)S, the phenyl ring is aligned at 6.9 (1) degrees and the phenyl-ene ring at 2.4 (1) degrees , so that the three rings are nearly coplanar. The amino group has the N atom in a pyramidal geometry; the group is a hydrogen-bond donor to the sulfonyl O atom of one mol-ecule and to the ketonic O atom of another mol-ecule, resulting in the formation of a layer parallel to the bc plane. PMID- 22064811 TI - Tetra-aqua-bis-(2-methyl-1H-benzimidazolium-1,3-diacetato-kappaO)cobalt(II) tetra hydrate. AB - In the title compound, [Co(C(12)H(11)N(2)O(4))(2)(H(2)O)(4)].4H(2)O, the Co(II) atom lies on an inversion center and is octa-hedrally coordinated by six O atoms from four water mol-ecules and two monodentate zwitterionic 2-methyl benzimidazolium-1,3-diacetate ligands. An intra-molecular O-H?O hydrogen bond occurs. In the crystal, inter-molecular O-H?O hydrogen bonds link the mol-ecules into a three-dimensional network. pi-pi inter-actions between the imidazole and benzene rings [centroid-centroid distance = 3.9031 (17) A] consolidate the crystal packing. PMID- 22064812 TI - Poly[(MU(5)-5-amino-isophthalato)aqua-barium]. AB - In the title compound, [Ba(C(8)H(5)NO(4))(H(2)O)](n), the Ba(II) ion is eight coordinated by six O atoms and one N atom from five 5-amino-isophthalate ligands and one water mol-ecule in a distorted dodeca-hedral geometry. The Ba(II) ions are connected via the ligands into a layer parallel to (011). The layers are linked by N-H?O hydrogen bonds. The coordinated water mol-ecule is involved in intra-layer O-H?O hydrogen bonds. PMID- 22064813 TI - Identification of patients at high risk for hypocalcemia after total thyroidectomy. AB - Hypocalcemia is a major post-operative complication of total thyroidectomy, causing severe symptoms and increasing hospitalization time. The primary cause is secondary hypo-parathyroidism following damage to, or devascularisation of, one or more parathyroid glands during surgery. Aim of the study was to develop a simple and reliable method for predicting post-operative hypocalcemia in total thyroidectomy patients. A retrospective analysis was made of immediate pre operative and early post-operative calcium levels in 100 patients. It was found that a marked decrease in blood calcium, immediately after surgery, was a sensitive predictor of hypocalcemia. In a subsequent prospective series of 67 patients, the efficacy was assessed of early administration of calcium plus Vitamin D in reducing symptomatic hypocalcemia in patients in whom the difference (Delta) between pre- and post-operative blood calcium was >= 1.1 mg/dl. This treatment was part of a protocol in which normo-calcemic patients were discharged immediately after drainage removal (third post-operative day). In the retrospective series, 84% of patients who developed hypocalcemia had Delta >= 1.1 and 54% of patients who did not develop hypocalcemia had Delta < 1.1 (p < 0.0001). Mean duration of hospitalization was 6.2 days. In the prospective series, 76% of patients who developed hypocalcemia had Delta >= 1.1 mg/dl; of the patients who did not develop hypocalcemia 75% had Delta < 1.1 mg/dl (p = 0.0013); mean hospitalization was 4.7 days (p < 0.0001). Use of the 1.1 mg/dl cut-off for deciding whether to start early prophylaxis allowed most patients to avoid symptomatic hypocalcemia (and the associated anxiety), while permitting a significantly reduced hospital stay, resulting in lower hospitalization costs. PMID- 22064814 TI - Dichlorido(2,3-di-2-pyridyl-pyrazine-kappaN,N)platinum(II). AB - The Pt(II) ion in the title complex, [PtCl(2)(C(14)H(10)N(4))], is four coordinated in a distorted square-planar environment by two N atoms of a chelating 2,3-di-2-pyridyl-pyrazine ligand and two chloride anions. The pyridyl ring coordinated to the Pt(II) atom is inclined slightly to its carrier pyrazine ring [dihedral angle = 13.5 (1) degrees ], whereas the uncoordinated pyridyl ring is inclined considerably to the pyrazine ring [dihedral angle = 54.3 (2) degrees ]. The dihedral angle between the two pyridyl rings is 59.2 (2) degrees . In the crystal, the complexes are assembled through inter-molecular C-H?N and C-H?Cl hydrogen bonds, forming a three-dimensional network. Intra-molecular C-H?N and C H?Cl hydrogen bonds are also present. PMID- 22064815 TI - Przewalski's Horse (Equus ferus przewalskii) Re-introduction in the Great Gobi B Strictly Protected Area: from Species to Ecosystem Conservation. AB - The Przewalski's horse (Equus ferus przewalskii Poljakov, 1881), or "Takhi" in Mongolian, became extinct in the wild by the mid 1960's. The last recorded sightings of Przewalski's horses occurred in the Dzungarian Gobi desert in SW Mongolia, today's Great Gobi B Strictly Protected Area (SPA). A re-introduction program was initiated in 1992 and the first group of captive-born Przewalski's horses was airlifted to the SPA. Given the logistical challenges associated with such a venture, the initial project focus has been on transport logistics and the well-being of the re-introduced horses. Today, conservation efforts are spread over the entire protected area. Present day efforts include other mammals, vegetation and the local people. Due to its important symbolic value in Mongolian culture, the Przewalski's horse became an important flagship species for the protected area's conservation and management. PMID- 22064816 TI - (E)-1-(2-Amino-phen-yl)-3-(3,4,5-trimeth-oxy-phen-yl)prop-2-en-1-one. AB - In the asymmetric unit of the title chalcone derivative, C(18)H(19)NO(4), there are three crystallographically independent mol-ecules (mol-ecules A, B and C). In mol-ecule A, the dihedral angle between two benzene rings is 12.22 (10) degrees and the plane of the central prop-2-en-1-one unit makes dihedral angles of 11.02 (13) and 2.64 (12) degrees with the two adjacent benzene rings. The corresponding angles in mol-ecule B are 12.35 (10), 18.78 (12) and 7.29 (12) degrees , respectively, and those in mol-ecule C are 15.40 (10), 15.62 (3) and 3.19 (13) degrees . In each mol-ecule, an intra-molecular N-H?O hydrogen bond generates an S(6) ring motif. In the crystal structure, the mol-ecules B are linked by inter-molecular N-H?O hydrogen bonds into a zigzag chain along the c axis, while the mol-ecules A and C are linked together via an N-H?O hydrogen bond into a dimer. Adjacent dimers are further connected by N-H?N hydrogen bonds into a three-dimensional network. Weak C-H?O and C-H?pi inter-actions are also observed. PMID- 22064817 TI - Bis(MU-2-phen-oxy-propionato-kappaO:O')bis-[(1,10-phenanthroline-kappaN,N')bis-(2 phen-oxy-propionato-kappaO,O')samarium(III)]. AB - The dimeric title compound, [Sm(2)(C(9)H(9)O(3))(6)(C(12)H(8)N(2))(2)], is centrosymmetric and is composed of six 2-phen-oxy-propionate anions and two 1,10 phenanthroline ligands. The Sm(III) atom is coordinated by two O atoms from two bridging anions, four O atoms from two chelating anions and the N atoms of the N heterocycle in a distorted dodeca-hedral geometry. PMID- 22064818 TI - 4-[2-(4-Bromo-phen-yl)hydrazinyl-idene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1 carbothio-amide. AB - In the title compound, C(11)H(10)BrN(5)OS, the approximately planar pyrazole ring [maximum deviation = 0.014 (2) A] forms a dihedral angle of 5.49 (13) degrees with the benzene ring. An intra-molecular N-H?O hydrogen bond generates an S(6) ring motif. In the crystal, mol-ecules are linked through inter-molecular N-H?S and N-H?O hydrogen bonds, forming a two-dimensional network parallel to (100). A short Br?Br contact of 3.5114 (6) A is also observed. PMID- 22064819 TI - 3-Benzyl-2-phenyl-1,3-thia-zolidin-4-one. AB - In the title compound, C(16)H(15)NOS, the thia-zolidine ring, which is essentially planar [maximum deviation = 0.071 (2) A], makes dihedral angles of 88.01 (8) and 87.21 (8) degrees with the terminal phenyl rings. The dihedral angle between the phenyl rings is 49.45 (5) degrees . In the crystal, mol-ecules are linked by a weak inter-molecular C-H?O hydrogen bond, forming a supra molecular chain along the b axis. Furthermore, the crystal packing is stabilized by a weak C-H?pi inter-action. PMID- 22064820 TI - Laryngeal debridement: an alternative treatment for a laryngopyocele presenting with severe airway obstruction. AB - The laryngocele is an abnormal saccular dilatation of the ventricle of Morgagni, which maintains its communication with the laryngeal vestibule. Three types of laryngoceles have been described: internal, external, and combined or mixed in relation to the position of the sac with respect to the thyrohyoid membrane. If the laryngocele becomes obstructed and infected it leads to the so-called laryngopyocele which, although a rare disease (8% of laryngoceles), can become an emergency causing severe airway obstruction needing urgent management, even tracheostomy. An alternative method is presented of emergency management of an internal laryngopyocele causing severe airway obstruction using a laryngeal microdebrider and avoiding tracheostomy. PMID- 22064821 TI - Development of naphtho[1,2-b:5,6-b']dithiophene based novel small molecules for efficient bulk-heterojunction organic solar cells. AB - Two new small molecules with a rigid planar naphtho[1,2-b:5,6-b']dithiophene (NDT) unit were designed and synthesized. Solution processed bulk-hetereojunction organic solar cells based on blends of the small molecules and [6,6]-phenyl-C(71) butyric acid methyl ester (PC(71)BM) exhibited promising photovoltaic device performance with a maximum power conversion efficiency up to 2.20% under the illumination of AM 1.5G, 100 mW cm(-2). PMID- 22064822 TI - 1-(2,4,6-Triisopropyl-phen-yl)ethanone. AB - The title compound, C(17)H(26)O, is a di-ortho-alkyl substituted phenyl ethanone that exhibits a significant twisting of the ketone fragment relative to the aromatic ring [O-C-C-C torsion angle = 89.32 (17) degrees ] due to steric pressure from the ortho-isopropyl groups. One ortho- and the para-isopropyl group exhibit orientational disorder with a refined site occupancy factor of 0.562 (3):0.438 (3). PMID- 22064823 TI - catena-Poly[[bis-(nitrato-kappaO)cadmium]bis-[MU-1,4-bis-(pyridin-3-yl-meth oxy)benzene-kappaN:N']]. AB - In the title compound, [Cd(NO(3))(2)(C(18)H(16)N(2)O(2))(2)](n), the six coordinated Cd(II) ion is located on an inversion center and has a distorted octa hedral environment defined by four N atoms from four 1,4-bis-(pyridin-3-ylmeth oxy)benzene ligands and two O atoms from two nitrate anions. The ligands link the Cd(II) ions into a ribbon-like structure running along [201]. One O atom of the nitrate anion is disordered over two positions with site-occupancy factors of 0.59 (2) and 0.41 (2). PMID- 22064824 TI - 2-[(Indan-1-yl-idene)amino]-ethanol. AB - The five-membed ring of the title compound, C(11)H(13)NO, that is fused with the aromatic ring is approximately planar (r.m.s. deviation = 0.037 A) despite the presence of the sp(3)-hybrid-ized ethyl-ene linkage. The hy-droxy group of the N bound hy-droxy-ethyl chain serves as hydrogen-bond donor to the azomethine N atom of an adjacent mol-ecule, generating a hydrogen-bonded C(2)-symmetric dimer. PMID- 22064825 TI - (4R)-4-(Biphenyl-4-yl)-7-chloro-1,2,3,4-tetra-hydro-quinoline. AB - The title compound, C(21)H(18)ClN, was synthesized by an enanti-oselective Bronsted acid-catalysed transfer hydrogenation reaction. The six-membered heterocycle adopts a half-chair conformation. It has the biphenyl residue in an axial position. The two rings of the biphenyl residue are almost coplanar [dihedral angle = 2.65 (9) degrees ]. The crystal packing is stabilized by N-H?Cl hydrogen bonds, which connect the mol-ecules into chains running along the a axis. PMID- 22064826 TI - 2-{[2-(2-Hy-droxy-3-meth-oxy-benzyl-idene)hydrazin-1-yl-idene]meth-yl}-6-meth-oxy phenol. AB - The title compound, C(16)H(16)N(2)O(4), was obtained from the reaction of hydrazine hydrate and o-vanilin in absolute ethanol. The mol-ecule is almost planar (except for the methyl H atoms), with a mean deviation from the plane of 0.0259 A. The mol-ecular structure also exhibits an approximate non crystallographic twofold axis. Intra-molecular O-H?N hydrogen bonds occur. In the crystal, inter-molecular C-H?O hydrogen bonds generate mol-ecular zigzag sheets. The sheets stack through C-H?pi inter-actions, leading to a three-dimensional network. PMID- 22064827 TI - Chemoselective conversion of alpha-unbranched aldehydes to amides, esters, and carboxylic acids by NHC-catalysis. AB - Depending on the N-heterocyclic carbene catalyst utilized, alpha-unbranched aldehydes selectively provided amides, esters, or carboxylic acids through oxidation by NCS. The alpha-unbranched aldehyde underwent these reactions chemoselectively in the presence of an aromatic or alpha-branched aldehyde. PMID- 22064828 TI - Circulatory miR34a as an RNAbased, noninvasive biomarker for brain aging. AB - MicroRNAs in blood samples have been identified as an important class of biomarkers, which can reflect physiological changes from cancer to brain dysfunction. In this report we identify concordant increases in levels of expression of miR-34a in brain and two components of mouse blood samples, peripheral blood mononuclear cells (PBMCs) and plasma, from 2 day old neonates through young adulthood and mid-life to old age at 25 months. Levels of this microRNA's prime target, silent information regulator 1 (SIRT1), in brain and the two blood-derived specimens decrease with age inversely to miR-34a, starting as early as 4 months old, when appreciable tissue aging has not yet begun. Our results suggest that: 1. Increased miR-34a and the reciprocal decrease of its target, SIRT1, in blood specimens are the accessible biomarkers for age-dependent changes in brain; and 2. these changes are predictors of impending decline in brain function, as early as in young adult mice. PMID- 22064829 TI - Caloxanthone C: a pyran-oxanthone from the stem bark of Calophyllum soulattri. AB - THE TITLE COMPOUND [SYSTEMATIC NAME: 5,10-di-hy-droxy-2,2-di-methyl-12-(2-methyl but-3-en-2-yl)-pyrano[3,2-b]xanthen-6(2H)-one], C(23)H(22)O(5), isolated from the stem bark of Calophyllum soulattri, consists of four six-membered rings and a 2 methyl-but-3-en-2-yl side chain. The tricyclic xanthone ring system is almost planar [maximum deviation = 0.093 (2) A], whereas the pyran-oid ring is in a distorted boat conformation. The 2-methyl-but-3-en-2-yl side chain is in a synperiplanar conformation. There are two intra-molecular O-H?O hydrogen bonds. In the crystal, mol-ecules are linked by C-H?O inter-actions, forming a zigzag chain propagating in [010]. PMID- 22064830 TI - Label-free visual detection of nucleic acids in biological samples with single base mismatch detection capability. AB - We have combined an allosteric molecular beacon for target recognition and guanine-rich DNAzyme for signal amplification to develop a new platform for visual detection of nucleic acids with single-base mismatch detection capability. The fully DNA-structured platform can undergo color change in response to target DNA/RNA, which enables sensitive and selective visual detection in biological samples. PMID- 22064831 TI - 4-((E)-{2-[N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)carboximido yl]benzyl-idene}amino)-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one. AB - The title compound, C(30)H(28)N(6)O(2), is a symmetric diimine derived from ortho dibenzaldehyde. Both C=N bonds are (E)-configured. The terminal N-bonded phenyl groups adopt staggered conformations relative to their respective parent heterocycles, the relevant least-squares planes inter-sect at angles of 32.35 (11) and 38.59 (10) degrees . In the crystal, C-H?O contacts connect the mol ecules into chains along the b axis and give rise to a C(1) (1)(14)C(1) (1)(14) and a R(2) (2)(12) pattern on different levels of graph-set analysis. The shortest inter-centroid distance between two centroids was found at 4.2074 (11) A between the two five-membered heterocycles. PMID- 22064832 TI - Poly[[tetra-MU(3)-acetato-hexa-MU(2)-acetato-diaqua-MU(2)-oxalato-tetra lanthanum(III)] dihydrate]. AB - The title compound, {[La(4)(CH(3)CO(2))(10)(C(2)O(4))(H(2)O)(2)].2H(2)O}(n), exhibits a two-dimensional layered structure with the oxalate and acetate ligands acting as bridges. The asymmetric unit contains two crystallographically independent lanthanum(III) ions, half of an oxalate ligand, five acetate ligands, one coordinated water mol-ecule and one uncoordinated water mol-ecule. The coordination numbers of the two La ions are 9 and 10. Adjacent layers of the structure, which extend parallel to (100), are linked by O-H?O hydrogen bonds and are also held together by van der Waals inter-actions between the CH(3) groups of the acetate anions. PMID- 22064834 TI - (2Z)-1-(5-Hy-droxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-3-(4-meth-oxy-anilino)but-2 en-1-one. AB - The central residue in the title compound, C(21)H(21)N(3)O(3), is close to planar (r.m.s. deviation = 0.0753 A for all non-H atoms from OH to NH inclusive): the hy droxy, amino and carbonyl groups all lie to the same side of the mol-ecule (the conformation about the ethene bond is Z), facilitating the formation of intra molecular O-H?O and N-H?O hydrogen bonds that close S(6) rings. However, overall the mol-ecule is twisted as the terminal aromatic rings are not coplanar with the central plane [dihedral angles = 20.55 (5) and 80.90 (4) degrees for the N-bound phenyl ring and the meth-oxy-benzene ring, respectively]. The dihedral angle between the rings is 82.14 (7) degrees . Supra-molecular layers in the ac plane mediated by C-H?pi inter-actions are found in the crystal. PMID- 22064833 TI - Abrogation of PIK3CA or PIK3R1 reduces proliferation, migration, and invasion in glioblastoma multiforme cells. AB - Glioblastoma multiforme (GBM) is a highly invasive and deadly brain tumor. Tumor cell invasion makes complete surgical resection impossible and reduces the efficacy of other therapies. Genome-wide analyses of mutations, copy-number changes, and expression patterns have provided new insights into genetic abnormalities common in GBM. We analyzed published data and identified the invasion and motility pathways most frequently altered in GBM. These were most notably the focal adhesion and integrin signaling, and extracellular matrix interactions pathways. We mapped alterations in each of these pathways and found that they included the catalytic PIK3CA and regulatory PIK3R1 subunit genes of the class IA PI3K. Knockdown of either of these genes separately in GBM cell lines by lentiviral-mediated shRNA expression resulted in decreased proliferation, migration, and invasion in all lines tested. FAK activity was reduced by knockdown of either PIK3CA or PIK3R1, and MMP2 levels were reduced by knockdown of PIK3R1. We conclude that PIK3R1, like PIK3CA, is a potential therapeutic target in GBM and that it also influences tumor cell growth and motility. PMID- 22064835 TI - Effects of total solar eclipse on mental patients-a clinicobiochemical correlation. AB - Thirteen treated psychotic cases comprising of eight schizophrenic, four M.D.P. (manic type) and one M. D. P. (depressive type), who were clinically symptom free, were studied in respect of their hormones and behavioural abnormalities under effect of total solar eclipse. Of the hormones studied viz., T(2), T(4), TSH, Cortisol and prolactin, it is prolactin which showed an increase in titre associated with behavioural abnormalities in concerned patients during and immediately after the total solar eclipse. Deflection in both prolactin and behaviour gradually seemed to normalise over the post eclipse period. PMID- 22064836 TI - 9-(Pent-4-en-yl)anthracene. AB - In the title compound, C(19)H(18), the anthracene system is almost planar, with a maximum deviation of -0.039 (1) A. The structure is stabilized by C-H?pi inter actions. The pentene moiety is not planar and is twisted away from the attached anthracene system with a maximum torsion angle of 91.2 (1) degrees . PMID- 22064837 TI - Poly[[tetra-aqua-bis-(MU(3)-pyridine-2,6-dicarboxyl-ato)(MU(2)-pyridine-2,6 dicarboxyl-ato)dilanthanum(III)] dihydrate]. AB - There are two independent La(III) cations in the polymeric title compound, {[La(2)(C(7)H(3)NO(4))(3)(H(2)O)(4)].2H(2)O}(n). One is nine-coordinated in an LaN(2)O(7) tricapped trigonal-prismatic geometry formed by three pyridine-2,6 dicarboxyl-ate anions and two water mol-ecules, while the other is ten coordinated in an LaNO(9) bicapped square-anti-prismatic geometry formed by four pyridine-2,6-dicarboxyl-ate anions and two water mol-ecules. The two La(III) cations are separated by a non-bonding distance of 5.026 (3) A. The pyridine-2,6 dicarboxyl-ate anions bridge the La(III) cations, forming a three-dimensional polymeric complex. The crystal structure contains extensive classical O-H?O hydrogen bonds and weak inter-molecular C-H?O hydrogen bonds. The crystal structure is further consolidated by pi-pi stacking between pyridine rings, the shortest centroid-centroid distance between parallel pyridine rings being 3.700 (5) A. PMID- 22064838 TI - 2-(1H-Benzotriazol-1-yl)-3-(2,6-dichloro-phen-yl)-1-phenyl-propan-1-ol. AB - The asymmetric unit of the title compound, C(21)H(17)Cl(2)N(3)O, contains two crystallographically independent mol-ecules with similar conformations. The benzotriazole ring is oriented at dihedral angles of 30.61 (5) and 43.36 (5) degrees , respectively, to the phenyl and dichloro-phenyl rings in one mol-ecule, and 32.25 (5) and 41.04 (5) degrees in the other. The dihedral angles between the phenyl and dichloro-phenyl rings are 66.38 (7) and 66.14 (6) degrees in the two mol-ecules. An intra-molecular O-H?N hydrogen bond links the benzotriazole ring and phenyl-propanol unit in each mol-ecule. In the crystal, weak inter molecular C-H?N hydrogen bonds link the mol-ecules into chains along the a axis. pi-pi stacking between the dichloro-phenyl rings [centroid-centroid distances = 3.809 (1) and 3.735 (1) A] may further stabilize the crystal structure. PMID- 22064839 TI - (E)-Methyl 3-(4-chloro-phen-yl)-2-{2-[(E)-(hy-droxy-imino)-meth-yl]phen-oxy-meth yl}acrylate. AB - In the title compound, C(18)H(16)ClNO(4), the dihedral angle between the mean planes through the aromatic rings is 83.8 (8) degrees . The hy-droxy-ethanimine group is essentially coplanar with the ring to which it is attached [O-N-C-C torsion angle = -177.96 (13) degrees ]. The mol-ecules are linked into centrosymmetric R(2) (2)(6) dimers via O-H?N hydrogen bonds. The crystal packing is further stabilized by C-H?O inter-actions. PMID- 22064840 TI - Correlation between female sex and allergy was significant in patients presenting with dysphonia. AB - Aim of the present study was to investigate the prevalence of allergy in patients affected by both organic and/or functional vocal fold disorders. The secondary aim was to assess the correlation between sex and allergy in dysphonic patients. A retrospective chart review was performed on dysphonic patients. A total of 76 patients underwent fiberoptic endoscopy to assess the objective picture. Logistic regression analyses have been conducted to assess the association between sex and the outcome variables. The laryngoscopic examination revealed the presence of poor glottic closure in 32.9%, hyperkinesias in 11.8%, redness in 11.84%, polyps in 5.3%, oedema in 3.95%, vocal fold hypertrophy in 5.3%, nodules in 42.1%, cordectomy in 2.6%. Allergic rhinitis was present in 56.6%, milk intolerance in 13.2%, asthma in 9.2%, atopic dermatitis in 3.9%, drugs intolerance in 11.8%. A total of 76.32% patients presenting with dysphonia were allergic. A statistically significant association was found between female sex and presence of allergy. In conclusion, allergy testing should be performed routinely on female professional voice users. Mild respiratory disorders must be taken into serious consideration in female professional voice users, who may primarily complain of vocal dysfunction rather than upper and lower respiratory diseases. PMID- 22064841 TI - Poly[[bis-(dimethyl-formamide)[MU(7)-5,5'-(methyl-enedi oxy)diisophthalato]dizinc] dimethyl-formamide monosolvate]. AB - In the crystal structure of the title coordination polymer, {[Zn(2)(C(17)H(8)O(10))(C(3)H(7)NO)(2)].C(3)H(7)NO}(n), the mol-ecular build-ing block (MBB), viz. {Zn(2)(CO(2))(4)(C(3)H(7)NO)(2)}, comprises two zinc atoms, each bridged by three carboxyl-ate groups. These two Zn atoms exhibit different coordination environments: a distorted coordination intermediate between trigonal pyramidal, and square-pyramidal formed by the two coordinated dimethyl-formamide mol-ecules and three carboxylate groups, and a distorted tetra-hedral coordination defined by carboxy-late groups of which three are bidentate bridging and the fourth is a monodentate ligand. Thus, each ligand connects four MBBs, forming the three-dimensional polymer. PMID- 22064842 TI - Radial shrinkage and ultrasound acoustic emissions of fresh versus pre-dried Norway spruce sapwood. AB - Acoustic emission (AE) and radial shrinkage were compared between fully saturated fresh and pre-dried Norway spruce sapwood during dehydration at ambient temperature. Hydraulic conductivity measurements, anatomical investigations on bordered pits and X-ray computed tomography (CT) scans were done to search for possible AE sources other than the breakage of the water columns inside the tracheids. Both fresh and pre-dried specimens showed radial shrinkage due to drying surface layers right from the beginning of dehydration, which induced almost no AE. Whereas no dimensional changes occurred in pre-dried wood thereafter, fresh wood showed a rapid shrinkage increase starting at 25% relative water loss. This dimensional change ceased when further moisture got lost and was even partially reversed. AE of fresh wood showed much higher activity and energy, which is a waveform feature that describes the strength of the acoustic signal. Extremely high single AE energy events were detected at this critical stage of dehydration. After partial recovery from shrinkage, neither dimensional changes nor AE activity showed differences between fresh and pre-dried wood after more than 80% relative moisture loss. Our results suggested that fresh sapwood is more prone to dehydration stresses than pre-dried sapwood. Differences in AE and shrinkage behavior might be due to the weakening or distortion of the pit membranes (cavitation fatigue), pit aspiration, structural changes of the cell walls and micro-checks, which occurred during the first dehydration cycle. PMID- 22064843 TI - 6-Meth-oxy-2-methyl-1-m-tolyl-1H-benzimidazole hemihydrate. AB - The title compound, C(16)H(16)N(2)O.0.5H(2)O, is a substituted 1-phenyl benzimidazole, which belongs to the class of ATP-site inhibitors of the platelet derived growth-factor receptor. In the crystal, the components are linked by an O H?N hydrogen bond. PMID- 22064844 TI - {5,5'-Bis(diethyl-amino)-2,2'-[(2,2-dimethyl-propane-1,3-di-yl)bis-(nitrilo methanylyl-idene)]diphenolato}dioxido-molybdenum(VI). AB - In the title compound, [Mo(C(27)H(38)N(4)O(2))O(2)], the Mo(VI) atom is coordinated by two oxide O atoms and by two O and two N atoms of the tetra dentate Schiff base ligand in a distorted octa-hedral geometry. The Mo-N bond trans to a terminal oxide group is significantly longer than the other Mo-N bond, which is attributed to the strong trans effect of the oxide O atom. The dihedral angle formed between the substituted benzene rings is 71.79 (14) degrees . One of the ethyl groups is disordered over two sets of sites, with a refined site occupancy ratio of 0.588 (18):0.412 (18). PMID- 22064845 TI - trans-Tetra-carbonyl-bis-[tris-(4-fluoro-phen-yl)phosphane-kappaP]chromium(0). AB - In the title compound, [Cr(C(18)H(12)F(3)P)(2)(CO)(4)], the Cr atom is octa hedrally coordinated by four carbonyl ligands and the two tertiary phosphanes that are trans to each other. The Cr atom and two carbonyl groups are on a twofold axis. The benzene rings attached to the phospho-rus atom make dihedral angles of 80.32 (5), 52.91 (5) and 83.80 (5) degrees with each other. In the crystal, C-H?O and C-H?F inter-molecular inter-actions form an infinite three dimensional network. PMID- 22064846 TI - Catalytic reactions of chlorite with a polypyridylruthenium(II) complex: disproportionation, chlorine dioxide formation and alcohol oxidation. AB - cis-[Ru(2,9-Me(2)phen)(2)(OH(2))(2)](2+) reacts readily with chlorite at room temperature at pH 4.9 and 6.8. The ruthenium(II) complex can catalyze the disproportionation of chlorite to chlorate and chloride, the oxidation of chlorite to chlorine dioxide, as well as the oxidation of alcohols by chlorite. PMID- 22064847 TI - Hearing preservation surgery in acoustic neuroma. Slow progress and new strategies. AB - Quality and rate of preserved hearing are crucial to make hearing preservation surgery a viable treatment. A long-term experience with hearing preservation surgery, with tumour size and hearing as admission criteria, was evaluated to assess which size and hearing allowed a high rate of success. The hearing outcome in relation to size of tumour and pre-operative hearing was retrospectively reviewed in a consecutive series of 115 cases of sporadic acoustic neuroma which were operated on with hearing preservation surgery. Inclusion criteria were hearing with <= 30 dB pure tone average and >= 70% Speech Discrimination Score. The size was <= 15 mm in the first series of 51 cases, and <= 10 mm in the second series of 64 cases. Pre-operative and post-operative pure tone average were measured at 0.5 to 4.0 KHz, and speech discrimination score at <= 40 dB above perception. Post-operative hearing within 30 dB pure tone average and 70% speech discrimination score was considered socially useful hearing and successful outcome. The change to 40 dB pure tone average and 60% speech discrimination score from a pre-operative 30 pure tone average/70% speech discrimination score was considered an acceptable outcome. Patients with a tumour of <= 10 mm size in the cerebello-pontine-angle and hearing within 20 dB pure tone average/80% speech discrimination score had a success rate of 76%. Patients with hearing between the 20 dB pure tone average/80% speech discrimination score and 30 dB pure tone average/ 70% speech discrimination score had a success rate of 41%, which increased to 53% if the limit to success was set at 40 dB pure tone average/60% speech discrimination score. Patients with a tumour larger than 10 mm or hearing worse than 30 dB pure tone average/70% speech discrimination score had a poor preservation rate. In conclusion, hearing preservation surgery on a <= 10 mm acoustic neuroma with good hearing had a high rate of success and appeared to be a realistic treatment option which could be integrated with observation and radiotherapy in updated guidelines of treatment. PMID- 22064848 TI - Use of micellar mobile phases for the chromatographic determination of melamine in dietetic supplements. AB - Melamine is a nitrogen-rich industrial chemical which is occasionally used to increase the apparent protein content of different products destined for human and animal consumption. In this work, a liquid chromatographic procedure that uses micellar mobile phases of sodium dodecyl sulfate (SDS) buffered at pH 3, a C18 column and UV detection is reported for the determination of melamine in dietetic supplements. Samples were reconstituted with a SDS solution and were directly injected, thus avoiding long extraction and experimental procedures. Melamine was eluted in less than 10 min with no interference by other compounds of the matrices. The optimum mobile phase composition was taken by a chemometrical approach that considers the retention factor, efficiency and peak shape. Validation was performed following the indications of the European Commission (Decision 2002/657/EC). The following parameters were considered: linearity (0.02-100 MUg mL(-1); R(2) = 0.9996), intra- and inter-day precisions (<12.4%), accuracy (90.0-101.3%), and robustness (less than 9.8% and 5.1%, for retention time and peak area, respectively). The limits of detection and quantification were 9 and 20 ng mL(-1), respectively. Recoveries for several spiked samples were in the 85.8-114.3% range. These results indicate that the proposed methodology is useful for routine analysis of control quality of infant formula and adult dietetic supplements. PMID- 22064849 TI - Dual detection strategy for electrochemical analysis of glucose and nitrite using a partitionally modified electrode. AB - A dual-region modified electrode was designed and fabricated by means of partitioned electrodeposition of gold and platinum nanoparticles on an indium tin oxide (ITO) conductive glass for dual-component electrochemical detection. The two differently modified regions were assigned to detect two analytes, separately and simultaneously. The gold nanoparticle modified ITO region (AuNPs/ITO) was used for glucose detection while the platinum nanoparticle modified ITO region (PtNPs/ITO) for nitrite detection. The glucose oxidation peak current at 0.10 V on AuNPs/ITO exhibited a linear dependence on the concentration of glucose and was used to determine the concentration of glucose in dual-detection. The nitrite reduction peak current at PtNPs/ITO showed a nonlinear dependence on the concentration of nitrite. A theoretical model combining the adsorption-controlled and the mass-transfer-controlled kinetics was proposed to quantitatively describe the nonlinear behavior. Though the presence of glucose interfered with the electrochemical detection of nitrite, it was demonstrated that the influence of glucose on nitrite detection can be corrected. On the basis of the proposed theoretical model, the simultaneous dual-detection of glucose and nitrite was accomplished at ITO electrodes partitionally modified with AuNPs and PtNPs. PMID- 22064850 TI - Calcium platinum aluminium, CaPtAl. AB - A preliminary X-ray study of CaPtAl has been reported previously by Hulliger [J. Alloys Compd (1993), 196, 225-228] based on X-ray powder diffraction data without structure refinement. With the present single-crystal X-ray study, we confirm the assignment of the TiNiSi type for CaPtAl, in a fully ordered inverse structure. All three atoms of the asymmetric unit have .m. site symmetry. The structure features a (infinity) (3)[AlPt] open framework with a fourfold coordination of Pt by Al atoms and vice versa. The Ca atoms are located in the large channels of the structure. PMID- 22064851 TI - HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. AB - The resolution of genome-wide association studies (GWAS) is limited by the linkage disequilibrium (LD) structure of the population being studied. Selecting the most likely causal variants within an LD block is relatively straightforward within coding sequence, but is more difficult when all variants are intergenic. Predicting functional non-coding sequence has been recently facilitated by the availability of conservation and epigenomic information. We present HaploReg, a tool for exploring annotations of the non-coding genome among the results of published GWAS or novel sets of variants. Using LD information from the 1000 Genomes Project, linked SNPs and small indels can be visualized along with their predicted chromatin state in nine cell types, conservation across mammals and their effect on regulatory motifs. Sets of SNPs, such as those resulting from GWAS, are analyzed for an enrichment of cell type-specific enhancers. HaploReg will be useful to researchers developing mechanistic hypotheses of the impact of non-coding variants on clinical phenotypes and normal variation. The HaploReg database is available at http://compbio.mit.edu/HaploReg. PMID- 22064852 TI - eQuilibrator--the biochemical thermodynamics calculator. AB - The laws of thermodynamics constrain the action of biochemical systems. However, thermodynamic data on biochemical compounds can be difficult to find and is cumbersome to perform calculations with manually. Even simple thermodynamic questions like 'how much Gibbs energy is released by ATP hydrolysis at pH 5?' are complicated excessively by the search for accurate data. To address this problem, eQuilibrator couples a comprehensive and accurate database of thermodynamic properties of biochemical compounds and reactions with a simple and powerful online search and calculation interface. The web interface to eQuilibrator (http://equilibrator.weizmann.ac.il) enables easy calculation of Gibbs energies of compounds and reactions given arbitrary pH, ionic strength and metabolite concentrations. The eQuilibrator code is open-source and all thermodynamic source data are freely downloadable in standard formats. Here we describe the database characteristics and implementation and demonstrate its use. PMID- 22064853 TI - A cross-sample statistical model for SNP detection in short-read sequencing data. AB - Highly multiplex DNA sequencers have greatly expanded our ability to survey human genomes for previously unknown single nucleotide polymorphisms (SNPs). However, sequencing and mapping errors, though rare, contribute substantially to the number of false discoveries in current SNP callers. We demonstrate that we can significantly reduce the number of false positive SNP calls by pooling information across samples. Although many studies prepare and sequence multiple samples with the same protocol, most existing SNP callers ignore cross-sample information. In contrast, we propose an empirical Bayes method that uses cross sample information to learn the error properties of the data. This error information lets us call SNPs with a lower false discovery rate than existing methods. PMID- 22064854 TI - The CHR promoter element controls cell cycle-dependent gene transcription and binds the DREAM and MMB complexes. AB - Cell cycle-dependent gene expression is often controlled on the transcriptional level. Genes like cyclin B, CDC2 and CDC25C are regulated by cell cycle-dependent element (CDE) and cell cycle genes homology region (CHR) promoter elements mainly through repression in G(0)/G(1). It had been suggested that E2F4 binding to CDE sites is central to transcriptional regulation. However, some promoters are only controlled by a CHR. We identify the DREAM complex binding to the CHR of mouse and human cyclin B2 promoters in G(0). Association of DREAM and cell cycle dependent regulation is abrogated when the CHR is mutated. Although E2f4 is part of the complex, a CDE is not essential but can enhance binding of DREAM. We show that the CHR element is not only necessary for repression of gene transcription in G(0)/G(1), but also for activation in S, G(2) and M phases. In proliferating cells, the B-myb-containing MMB complex binds the CHR of both promoters independently of the CDE. Bioinformatic analyses identify many genes which contain conserved CHR elements in promoters binding the DREAM complex. With Ube2c as an example from that screen, we show that inverse CHR sites are functional promoter elements that can bind DREAM and MMB. Our findings indicate that the CHR is central to DREAM/MMB-dependent transcriptional control during the cell cycle. PMID- 22064855 TI - YMDB: the Yeast Metabolome Database. AB - The Yeast Metabolome Database (YMDB, http://www.ymdb.ca) is a richly annotated 'metabolomic' database containing detailed information about the metabolome of Saccharomyces cerevisiae. Modeled closely after the Human Metabolome Database, the YMDB contains >2000 metabolites with links to 995 different genes/proteins, including enzymes and transporters. The information in YMDB has been gathered from hundreds of books, journal articles and electronic databases. In addition to its comprehensive literature-derived data, the YMDB also contains an extensive collection of experimental intracellular and extracellular metabolite concentration data compiled from detailed Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) metabolomic analyses performed in our lab. This is further supplemented with thousands of NMR and MS spectra collected on pure, reference yeast metabolites. Each metabolite entry in the YMDB contains an average of 80 separate data fields including comprehensive compound description, names and synonyms, structural information, physico-chemical data, reference NMR and MS spectra, intracellular/extracellular concentrations, growth conditions and substrates, pathway information, enzyme data, gene/protein sequence data, as well as numerous hyperlinks to images, references and other public databases. Extensive searching, relational querying and data browsing tools are also provided that support text, chemical structure, spectral, molecular weight and gene/protein sequence queries. Because of S. cervesiae's importance as a model organism for biologists and as a biofactory for industry, we believe this kind of database could have considerable appeal not only to metabolomics researchers, but also to yeast biologists, systems biologists, the industrial fermentation industry, as well as the beer, wine and spirit industry. PMID- 22064856 TI - NucleaRDB: information system for nuclear receptors. AB - The NucleaRDB is a Molecular Class-Specific Information System that collects, combines, validates and disseminates large amounts of heterogeneous data on nuclear hormone receptors. It contains both experimental and computationally derived data. The data and knowledge present in the NucleaRDB can be accessed using a number of different interactive and programmatic methods and query systems. A nuclear hormone receptor-specific PDF reader interface is available that can integrate the contents of the NucleaRDB with full-text scientific articles. The NucleaRDB is freely available at http://www.receptors.org/nucleardb. PMID- 22064857 TI - FungiDB: an integrated functional genomics database for fungi. AB - FungiDB (http://FungiDB.org) is a functional genomic resource for pan-fungal genomes that was developed in partnership with the Eukaryotic Pathogen Bioinformatic resource center (http://EuPathDB.org). FungiDB uses the same infrastructure and user interface as EuPathDB, which allows for sophisticated and integrated searches to be performed using an intuitive graphical system. The current release of FungiDB contains genome sequence and annotation from 18 species spanning several fungal classes, including the Ascomycota classes, Eurotiomycetes, Sordariomycetes, Saccharomycetes and the Basidiomycota orders, Pucciniomycetes and Tremellomycetes, and the basal 'Zygomycete' lineage Mucormycotina. Additionally, FungiDB contains cell cycle microarray data, hyphal growth RNA-sequence data and yeast two hybrid interaction data. The underlying genomic sequence and annotation combined with functional data, additional data from the FungiDB standard analysis pipeline and the ability to leverage orthology provides a powerful resource for in silico experimentation. PMID- 22064858 TI - Crystal structure of the NurA-dAMP-Mn2+ complex. AB - Generation of the 3' overhang is a critical event during homologous recombination (HR) repair of DNA double strand breaks. A 5'-3' nuclease, NurA, plays an important role in generating 3' single-stranded DNA during archaeal HR, together with Mre11-Rad50 and HerA. We have determined the crystal structures of apo- and dAMP-Mn(2)(+)-bound NurA from Pyrococcus furiousus (Pf NurA) to provide the basis for its cleavage mechanism. Pf NurA forms a pyramid-shaped dimer containing a large central channel on one side, which becomes narrower towards the peak of the pyramid. The structure contains a PIWI domain with high similarity to argonaute, endoV nuclease and RNase H. The two active sites, each of which contains Mn(2)(+) ion(s) and dAMP, are at the corners of the elliptical channel near the flat face of the dimer. The 3' OH group of the ribose ring is directed toward the channel entrance, explaining the 5'-3' nuclease activity of Pf NurA. We provide a DNA binding and cleavage model for Pf NurA. PMID- 22064859 TI - Direct evidence of nuclear Argonaute distribution during transcriptional silencing links the actin cytoskeleton to nuclear RNAi machinery in human cells. AB - Mammalian RNAi machinery facilitating transcriptional gene silencing (TGS) is the RNA-induced transcriptional gene silencing-like (RITS-like) complex, comprising of Argonaute (Ago) and small interfering RNA (siRNA) components. We have previously demonstrated promoter-targeted siRNA induce TGS in human immunodeficiency virus type-1 (HIV-1) and simian immunodeficiency virus (SIV), which profoundly suppresses retrovirus replication via heterochromatin formation and histone methylation. Here, we examine subcellular co-localization of Ago proteins with promoter-targeted siRNAs during TGS of SIV and HIV-1 infection. Analysis of retrovirus-infected cells revealed Ago1 co-localized with siRNA in the nucleus, while Ago2 co-localized with siRNA in the inner nuclear envelope. Mismatched and scrambled siRNAs were observed in the cytoplasm, indicating sequence specificity. This is the first report directly visualizing nuclear compartment distribution of Ago-associated siRNA and further reveals a novel nuclear trafficking mechanism for RITS-like components involving the actin cytoskeleton. These results establish a model for elucidating mammalian TGS and suggest a fundamental mechanism underlying nuclear delivery of RITS-like components. PMID- 22064860 TI - YY1 associates with the macrosatellite DXZ4 on the inactive X chromosome and binds with CTCF to a hypomethylated form in some male carcinomas. AB - DXZ4 is an X-linked macrosatellite composed of 12-100 tandemly arranged 3-kb repeat units. In females, it adopts opposite chromatin arrangements at the two alleles in response to X-chromosome inactivation. In males and on the active X chromosome, it is packaged into heterochromatin, but on the inactive X chromosome (Xi), it adopts a euchromatic conformation bound by CTCF. Here we report that the ubiquitous transcription factor YY1 associates with the euchromatic form of DXZ4 on the Xi. The binding of YY1 close to CTCF is reminiscent of that at other epigenetically regulated sequences, including sites of genomic imprinting, and at the X-inactivation centre, suggesting a common mode of action in this arrangement. As with CTCF, binding of YY1 to DXZ4 in vitro is not blocked by CpG methylation, yet in vivo both proteins are restricted to the hypomethylated form. In several male carcinoma cell lines, DXZ4 can adopt a Xi-like conformation in response to cellular transformation, characterized by CpG hypomethylation and binding of YY1 and CTCF. Analysis of a male melanoma cell line and normal skin cells from the same individual confirmed that a transition in chromatin state occurred in response to transformation. PMID- 22064861 TI - The LANL hemorrhagic fever virus database, a new platform for analyzing biothreat viruses. AB - Hemorrhagic fever viruses (HFVs) are a diverse set of over 80 viral species, found in 10 different genera comprising five different families: arena-, bunya-, flavi-, filo- and togaviridae. All these viruses are highly variable and evolve rapidly, making them elusive targets for the immune system and for vaccine and drug design. About 55,000 HFV sequences exist in the public domain today. A central website that provides annotated sequences and analysis tools will be helpful to HFV researchers worldwide. The HFV sequence database collects and stores sequence data and provides a user-friendly search interface and a large number of sequence analysis tools, following the model of the highly regarded and widely used Los Alamos HIV database [Kuiken, C., B. Korber, and R.W. Shafer, HIV sequence databases. AIDS Rev, 2003. 5: p. 52-61]. The database uses an algorithm that aligns each sequence to a species-wide reference sequence. The NCBI RefSeq database [Sayers et al. (2011) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res., 39, D38-D51.] is used for this; if a reference sequence is not available, a Blast search finds the best candidate. Using this method, sequences in each genus can be retrieved pre-aligned. The HFV website can be accessed via http://hfv.lanl.gov. PMID- 22064862 TI - The Candida genome database incorporates multiple Candida species: multispecies search and analysis tools with curated gene and protein information for Candida albicans and Candida glabrata. AB - The Candida Genome Database (CGD, http://www.candidagenome.org/) is an internet based resource that provides centralized access to genomic sequence data and manually curated functional information about genes and proteins of the fungal pathogen Candida albicans and other Candida species. As the scope of Candida research, and the number of sequenced strains and related species, has grown in recent years, the need for expanded genomic resources has also grown. To answer this need, CGD has expanded beyond storing data solely for C. albicans, now integrating data from multiple species. Herein we describe the incorporation of this multispecies information, which includes curated gene information and the reference sequence for C. glabrata, as well as orthology relationships that interconnect Locus Summary pages, allowing easy navigation between genes of C. albicans and C. glabrata. These orthology relationships are also used to predict GO annotations of their products. We have also added protein information pages that display domains, structural information and physicochemical properties; bibliographic pages highlighting important topic areas in Candida biology; and a laboratory strain lineage page that describes the lineage of commonly used laboratory strains. All of these data are freely available at http://www.candidagenome.org/. We welcome feedback from the research community at candida-curator@lists.stanford.edu. PMID- 22064863 TI - EcoliWiki: a wiki-based community resource for Escherichia coli. AB - EcoliWiki is the community annotation component of the PortEco (http://porteco.org; formerly EcoliHub) project, an online data resource that integrates information on laboratory strains of Escherichia coli, its phages, plasmids and mobile genetic elements. As one of the early adopters of the wiki approach to model organism databases, EcoliWiki was designed to not only facilitate community-driven sharing of biological knowledge about E. coli as a model organism, but also to be interoperable with other data resources. EcoliWiki content currently covers genes from five laboratory E. coli strains, 21 bacteriophage genomes, F plasmid and eight transposons. EcoliWiki integrates the Mediawiki wiki platform with other open-source software tools and in-house software development to extend how wikis can be used for model organism databases. EcoliWiki can be accessed online at http://ecoliwiki.net. PMID- 22064864 TI - Gene Expression Atlas update--a value-added database of microarray and sequencing based functional genomics experiments. AB - Gene Expression Atlas (http://www.ebi.ac.uk/gxa) is an added-value database providing information about gene expression in different cell types, organism parts, developmental stages, disease states, sample treatments and other biological/experimental conditions. The content of this database derives from curation, re-annotation and statistical analysis of selected data from the ArrayExpress Archive and the European Nucleotide Archive. A simple interface allows the user to query for differential gene expression either by gene names or attributes or by biological conditions, e.g. diseases, organism parts or cell types. Since our previous report we made 20 monthly releases and, as of Release 11.08 (August 2011), the database supports 19 species, which contains expression data measured for 19,014 biological conditions in 136,551 assays from 5598 independent studies. PMID- 22064865 TI - Interferon gamma (IFN-gamma) disrupts energy expenditure and metabolic homeostasis by suppressing SIRT1 transcription. AB - Chronic inflammation impairs metabolic homeostasis and is intimately correlated with the pathogenesis of type 2 diabetes. The pro-inflammatory cytokine IFN-gamma is an integral part of the metabolic inflammation circuit and contributes significantly to metabolic dysfunction. The underlying mechanism, however, remains largely unknown. In the present study, we report that IFN-gamma disrupts the expression of genes key to cellular metabolism and energy expenditure by repressing the expression and activity of SIRT1 at the transcription level. Further analysis reveals that IFN-gamma requires class II transactivator (CIITA) to repress SIRT1 transcription. CIITA, once induced by IFN-gamma, is recruited to the SIRT1 promoter by hypermethylated in cancer 1 (HIC1) and promotes down regulation of SIRT1 transcription via active deacetylation of core histones surrounding the SIRT1 proximal promoter. Silencing CIITA or HIC1 restores SIRT1 activity and expression of metabolic genes in skeletal muscle cells challenged with IFN-gamma. Therefore, our data delineate an IFN-gamma/HIC1/CIITA axis that contributes to metabolic dysfunction by suppressing SIRT1 transcription in skeletal muscle cells and as such shed new light on the development of novel therapeutic strategies against type 2 diabetes. PMID- 22064866 TI - Detection of recombination events in bacterial genomes from large population samples. AB - Analysis of important human pathogen populations is currently under transition toward whole-genome sequencing of growing numbers of samples collected on a global scale. Since recombination in bacteria is often an important factor shaping their evolution by enabling resistance elements and virulence traits to rapidly transfer from one evolutionary lineage to another, it is highly beneficial to have access to tools that can detect recombination events. Multiple advanced statistical methods exist for such purposes; however, they are typically limited either to only a few samples or to data from relatively short regions of a total genome. By harnessing the power of recent advances in Bayesian modeling techniques, we introduce here a method for detecting homologous recombination events from whole-genome sequence data for bacterial population samples on a large scale. Our statistical approach can efficiently handle hundreds of whole genome sequenced population samples and identify separate origins of the recombinant sequence, offering an enhanced insight into the diversification of bacterial clones at the level of the whole genome. A data set of 241 whole genome sequences from an important pandemic lineage of Streptococcus pneumoniae is used together with multiple simulated data sets to demonstrate the potential of our approach. PMID- 22064867 TI - Novel insights into FH-associated disease are KEAPing the lid on oncogenic HIF signalling. PMID- 22064868 TI - MU-Acetato-MU-(5-chloro-2-{1,3-bis[2-(5-chloro-2 oxidobenzylideneamino)ethyl]imidazolidin-2-yl}phenolato)-bis[methanolnickel(II)] methanol monosolvate monohydrate. AB - The crystal structure shows that the title compound, [Ni(2)(CH(3)CO(2))(C(27)H(24)Cl(3)N(4)O(3))(CH(4)O)(2)].CH(3)OH.H(2)O, con-tains [Ni(2)L(OAc)(CH(3)OH)(2)] mol-ecules in the unit cell {H(3)L = 5-chloro-2-{1,3 bis[2-(5-chloro-2-oxidobenzylideneimino)-ethyl]imidazolidin-2-yl}phenolate} with water and methanol as solvates. The title compound is a neutral dinuclear compound, in which the L(3-) Schiff base acts as a hepta-dentate ligand, using each one of its N(2)O compartments to coordinate a nickel atom. The acetate anion bridges the two nickel atoms via one O while the distorted octahedral coordination sphere for each nickel atom is completed by a coordinated methanol ligand. One of the coordinated methanol ligands is involved in an intra-molecular hydrogen bond to the uncoordinated O atom of the bridging acetate ligand while the other forms a hydrogen bond with the methanol solvate. The solvate water mol ecule forms strong hydrogen bonds to both terminal phenolato O atoms. The methanol solvate mol-ecule also forms a hydrogen bond with the water solvate mol ecule. PMID- 22064869 TI - 2,3-Dibromo-3-(4-chloro-phen-yl)-1-(2-hy-droxy-phen-yl)propan-1-one. AB - In the title mol-ecule, C(15)H(11)Br(2)ClO(2), an S(6) ring motif is formed via an intra-molecular O-H?O hydrogen bond. The dihedral angle formed between the chloro- and hy-droxy-substituted benzene rings is 34.10 (15) degrees . In the crystal, weak inter-molecular C-H?O hydrogen bonds link the mol-ecules into chains along the c axis. PMID- 22064870 TI - 1,1'-(Propane-1,3-di-yl)bis-(3-phenyl-urea). AB - The title compound, C(17)H(20)N(4)O(2), has crystallographic inversion symmetry. In the crystal structure, inter-molecular hydrogen bonding between adjacent urea groups gives rise to infinite polymeric chains diagonally across the bc plane. With a centroid-centroid distance of 3.295 (2) A, pi-pi stacking is present in the crystal along the same plane. PMID- 22064871 TI - Two consecutive click reactions as a general route to functional cyclic polyesters. AB - A simple and universal route to functional cyclic polyesters has been demonstrated, combining two consecutive click reactions of azide-alkyne cycloaddition of linear hetero-bifunctional precursors and thiol-ene coupling for post cyclization functionalizations. Functional cationic and thermo-responsive cyclic polyphosphoesters have been synthesized to demonstrate the efficiency of the procedures. PMID- 22064872 TI - The challenge of mental health care in pediatrics. PMID- 22064873 TI - Iron in infancy and long-term development. PMID- 22064874 TI - A randomized trial of single home nursing visits vs office-based care after nursery/maternity discharge: the Nurses for Infants Through Teaching and Assessment After the Nursery (NITTANY) Study. AB - OBJECTIVE: To compare office-based care (OBC) with a care model using a home nursing visit (HNV) as the initial postdischarge encounter for "well" breastfeeding newborns and mothers. DESIGN: Randomized controlled trial. SETTING: A single academic hospital. PARTICIPANTS: A total of 1154 postpartum mothers intending to breastfeed and their 1169 newborns of at least 34 weeks' gestation. INTERVENTIONS: Home nursing visits were scheduled no later than 2 days after discharge; OBC timing was physician determined. OUTCOME MEASURES: Mothers completed telephone surveys at 2 weeks, 2 months, and 6 months. The primary outcome was unplanned health care utilization for mothers and newborns within 2 weeks of delivery. Other newborn outcomes were proportion seen within 2 days after discharge and breastfeeding duration. Maternal mental health, parenting competence, and satisfaction with care outcomes were assessed. Analyses followed an intent-to-treat paradigm. RESULTS: At 2 weeks, hospital readmissions and emergency department visits were uncommon, and there were no study group differences in these outcomes or with unplanned outpatient visit frequency. Newborns in the HNV group were seen no more than 2 days after discharge more commonly than those in the OBC group (85.9% vs 78.8%) (P = .002) and were more likely to be breastfeeding at 2 weeks (92.3% vs 88.6%) (P = .04) and 2 months (72.1% vs 66.4%) (P = .05) but not 6 months. No group differences were detected for maternal mental health or satisfaction with care, but HNV group mothers had a greater parenting sense of competence (P < .01 at 2 weeks and 2 months). CONCLUSIONS: Home nursing visits are a safe and effective alternative to OBC for the initial outpatient encounter after maternity/nursery discharge with similar patterns of unplanned health care utilization and modest breastfeeding and parenting benefits. PMID- 22064875 TI - Banning all sugar-sweetened beverages in middle schools: reduction of in-school access and purchasing but not overall consumption. AB - OBJECTIVE: To determine whether state policies that regulate beverages in schools are associated with reduced in-school access and purchase of sugar-sweetened beverages (SSBs) and reduced consumption of SSBs (in and out of school) among adolescents. DESIGN: Cross-sectional. SETTING: Public schools in 40 states. PARTICIPANTS: Students sampled in fifth and eighth grades (spring 2004 and 2007, respectively). MAIN EXPOSURES: State policies that ban all SSBs and state policies that ban only soda for 2006-2007. MAIN OUTCOME MEASURES: In-school SSB access, in-school SSB purchasing behavior, and overall SSB consumption (in and out of school) in eighth grade. RESULTS: The proportions of eighth-grade students who reported in-school SSB access and purchasing were similar in states that banned only soda (66.6% and 28.9%, respectively) compared with states with no beverage policy (66.6% and 26.0%, respectively). In states that banned all SSBs, fewer students reported in-school SSB access (prevalence difference, -14.9; 95% CI, -23.6 to -6.1) or purchasing (-7.3; -11.0 to -3.5), adjusted for race/ethnicity, poverty status, locale, state obesity prevalence, and state clustering. Results were similar among students who reported access or purchasing SSBs in fifth grade compared with those who did not. Overall SSB consumption was not associated with state policy; in each policy category, approximately 85% of students reported consuming SSBs at least once in the past 7 days. Supplementary analyses indicated that overall consumption had only a modest association with in school SSB access. CONCLUSION: State policies that ban all SSBs in middle schools appear to reduce in-school access and purchasing of SSBs but do not reduce overall consumption. PMID- 22064876 TI - Doctor-office collaborative care for pediatric behavioral problems: a preliminary clinical trial. AB - OBJECTIVES: To evaluate the feasibility and clinical benefits of an integrated mental health intervention (doctor-office collaborative care [DOCC]) vs enhanced usual care (EUC) for children with behavioral problems. DESIGN: Cases were assigned to DOCC and EUC using a 2:1 randomization schedule that resulted in 55 DOCC and 23 EUC cases. SETTING: Preassessment was conducted in 4 pediatric primary care practices. Postassessment was conducted in the pediatric or research office. Doctor-office collaborative care was provided in the practice; EUC was initiated in the office but involved a facilitated referral to a local mental health specialist. PARTICIPANTS: Of 125 referrals (age range, 5-12 years), 78 children participated. INTERVENTIONS: Children and their parents were assigned to receive DOCC or EUC. MAIN OUTCOME MEASURES: Preassessment diagnostic status was evaluated using the Schedule for Affective Disorders and Schizophrenia for School aged Children. Preassessment and 6-month postassessment ratings of behavioral and emotional problems were collected from parents using the Vanderbilt Attention Deficit/Hyperactivity Disorder Diagnostic Parent Rating Scale, as well as individualized goal achievement ratings forms. At discharge, care managers and a diagnostic evaluator completed the Clinical Global Impression Scale, and pediatricians and parents completed satisfaction and study feedback measures. RESULTS: Group comparisons found significant improvements for DOCC over EUC in service use and completion, behavioral and emotional problems, individualized behavioral goals, and overall clinical response. Pediatricians and parents were highly satisfied with DOCC. CONCLUSION: The feasibility and clinical benefits of DOCC for behavioral problems support the integration of collaborative mental health services for common mental disorders in primary care. PMID- 22064877 TI - Iron-fortified vs low-iron infant formula: developmental outcome at 10 years. AB - OBJECTIVE: To assess long-term developmental outcome in children who received iron-fortified or low-iron formula. DESIGN: Follow-up at 10 years of a randomized controlled trial (1991-1994) of 2 levels of formula iron. Examiners were masked to group assignment. SETTING: Urban areas around Santiago, Chile. PARTICIPANTS: The original study enrolled healthy, full-term infants in community clinics; 835 completed the trial. At 10 years, 473 were assessed (56.6%). INTERVENTION: Iron fortified (mean, 12.7 mg/L) or low-iron (mean, 2.3 mg/L) formula from 6 to 12 months. MAIN OUTCOME MEASURES: We measured IQ, spatial memory, arithmetic achievement, visual-motor integration, visual perception, and motor functioning. We used covaried regression to compare iron-fortified and low-iron groups and considered hemoglobin level before randomization and sensitivity analyses to identify 6-month hemoglobin levels at which groups diverged in outcome. RESULTS: Compared with the low-iron group, the iron-fortified group scored lower on every 10-year outcome (significant for spatial memory and visual-motor integration; suggestive for IQ, arithmetic achievement, visual perception, and motor coordination; 1.4-4.6 points lower; effect sizes, 0.13-0.21). Children with high 6-month hemoglobin levels (> 12.8 g/dL [to convert to grams per liter, multiply by 10]) showed poorer outcome on these measures if they received iron-fortified formula (10.7-19.3 points lower; large effect sizes, 0.85-1.36); those with low hemoglobin levels (< 10.5 g/dL) showed better outcome (2.6-4.5 points higher; small but significant effects, 0.22-0.36). High hemoglobin levels represented 5.5% of the sample (n = 26) and low hemoglobin levels represented 18.4% (n = 87). CONCLUSION: Long-term development may be adversely affected in infants with high hemoglobin levels who receive 12.7 mg/L of iron-fortified formula. Optimal amounts of iron in infant formula warrant further study. PMID- 22064878 TI - Evaluation of the Web-based computer-tailored FATaintPHAT intervention to promote energy balance among adolescents: results from a school cluster randomized trial. AB - OBJECTIVE: To evaluate the short- and long-term results of FATaintPHAT, a Web based computer-tailored intervention aiming to increase physical activity, decrease sedentary behavior, and promote healthy eating to contribute to the prevention of excessive weight gain among adolescents. DESIGN: Cluster randomized trial with an intervention group and a no-intervention control group. SETTING: Twenty schools in the Netherlands. PARTICIPANTS: A total of 883 students (aged 12 13 years). INTERVENTION: The FATaintPHAT (VETisnietVET in Dutch) Web-based computer-tailored intervention. OUTCOME MEASURES: Self-reported behaviors (diet, physical activity, sedentary behavior) and pedometer counts were measured at baseline and at 4-month and 2-year follow-up; body mass index (BMI), waist circumference, and fitness were measured at baseline and at 2-year follow-up. Descriptive and multilevel regression analyses were conducted among the total study population and among students not meeting behavioral recommendations at baseline (students at risk). RESULTS: The complete case analyses showed that FATaintPHAT had no effect on BMI and waist circumference. However, the intervention was associated with lower odds (0.54) of drinking more than 400 mL of sugar-sweetened beverages per day and with lower snack intake (beta = -0.81 snacks/d) and higher vegetable intake (beta = 19.3 g/d) but also with a lower step count (beta = -10 856 steps/wk) at 4-month follow-up. In addition, among students at risk, FATaintPHAT had a positive effect on fruit consumption (beta = 0.39 g/d) at 4-month follow-up and on step count (beta = 14 228 steps/wk) at 2 year follow-up but an inverse effect on the odds of sports participation (odds ratio, 0.45) at 4-month follow-up. No effects were found for sedentary behavior. CONCLUSION: The FATaintPHAT intervention was associated with positive short-term effects on diet but with no effects or unfavorable effects on physical activity and sedentary behavior. PMID- 22064879 TI - Chronic disease: a national men's health problem. PMID- 22064880 TI - The economic burden shouldered by public and private entities as a consequence of health disparities between men and women. AB - On average, American men live shorter, less healthy lives than women. They are more likely to be the victim of a violent crime, die in a car crash, commit suicide, and be injured at work. In addition, men have higher death rates in 9 of the top 10 causes of death, and are less likely to receive routine preventative care, leaving men with a life span that is significantly shorter than women's. Recently, policy makers and researchers have been paying more attention to health disparities including race, sex, and ethnicity. However, men are still noticeably absent from these discussions despite being significantly harmed by disparities in preventive care, quality of life, and overall health outcomes. Ignoring these disparities is costly in terms of lost productivity, lives lost, and financial costs incurred by the government and employers each year. Premature death and morbidity in men costs federal, state, and local governments in excess of $142 billion annually. It also costs U.S.employers and society as a whole in excess of $156 billion annually in direct medical payments and lost productivity and an additional $181 billion annually in decreased quality of life. As federal and state governments and the private sector struggle with increasing health entitlement burdens-including escalating health care costs-eliminating male health inequities emerges as an important source of savings. This analysis will examine the economic and intangible costs associated with the health disparities that exist between genders and the benefits reaped if these disparities are reduced or eliminated. PMID- 22064881 TI - Circulating tumor cells in the cerebrospinal fluid: "tapping" into diagnostic and predictive potential. PMID- 22064882 TI - Genomic aberrations in pediatric diffuse intrinsic pontine gliomas. AB - Diagnostic biopsy is not routinely performed for children with diffuse intrinsic pontine glioma (DIPG). Consequently, our understanding of DIPG biology is hindered by limited tissue availability. We performed comparative genomic hybridization (CGH) on autopsy specimens to examine the feasibility of determining DNA genomic copy number aberrations on formalin-fixed, paraffin embedded (FFPE) blocks. Histology on FFPE blocks obtained from autopsy of pediatric patients with DIPG was reviewed. Regions were marked for processing, and DNA was extracted from the tissue core, labeled by chemical coupling with Cy5, and hybridized to 105K oligonucleotide CGH arrays. After hybridization and washing, arrays were scanned, and data segmented and processed with Nexus software. Twenty-two samples from 13 subjects were obtained. Histologic variability was noted. CGH was successfully performed on 18 of 22 samples, representing 11 of 13 subjects. All demonstrated DNA copy number abnormalities. High copy number amplification of known oncogenes and homozygous deletions of known tumor suppressor genes were observed. Additional regions of high copy number amplification and homozygous deletion and geographical variations in the CGH patterns were found. CGH performed on FFPE tissue obtained from autopsy yields satisfactory results. This sample set from patients with DIPG was highly informative, with the majority of specimens showing >=1 abnormality related to a known cancer gene. Aberrations in candidate drug targets were observed. This study establishes the feasibility of genomic DNA analysis from DIPG autopsy material, identifies several targets for which molecular targeted therapy exists, and suggests significant heterogeneity among patients with DIPG. PMID- 22064883 TI - Capture of double-stranded DNA in stacked-graphene: giving new insight into the graphene/DNA interaction. AB - Colloidal chemically converted graphene sheets (CCGs) are able to contact with each other to form stable self-assembled stacked-CCGs via salt "invasion", which can serve as powerful building blocks for capturing double-stranded DNA. PMID- 22064884 TI - Glutamate and tumor-associated epilepsy. PMID- 22064885 TI - (E)-2-[1-(4-Fluoro-phen-yl)pent-1-en-3-yl-idene]malononitrile. AB - The title mol-ecule, C(14)H(11)FN(2), is approximately planar except the ethyl group, the maximum atomic deviation being 0.105 (5) A. The fluoro-phenyl ring and 2-propyl-idene-malononitrile unit are located on the opposite sides of the C=C double bond, showing an E configuration. PMID- 22064886 TI - First principles based mean field model for oxygen reduction reaction. AB - A first principles-based mean field model was developed for the oxygen reduction reaction (ORR) taking account of the coverage- and material-dependent reversible potentials of the elementary steps. This model was applied to the simulation of single crystal surfaces of Pt, Pt alloy and Pt core-shell catalysts under Ar and O(2) atmospheres. The results are consistent with those shown by past experimental and theoretical studies on surface coverages under Ar atmosphere, the shape of the current-voltage curve for the ORR on Pt(111) and the material dependence of the ORR activity. This model suggests that the oxygen associative pathway including HO(2)(ads) formation is the main pathway on Pt(111), and that the rate determining step (RDS) is the removal step of O(ads) on Pt(111). This RDS is accelerated on several highly active Pt alloys and core-shell surfaces, and this acceleration decreases the reaction intermediate O(ads). The increase in the partial pressure of O(2)(g) increases the surface coverage with O(ads) and OH(ads), and this coverage increase reduces the apparent reaction order with respect to the partial pressure to less than unity. This model shows details on how the reaction pathway, RDS, surface coverages, Tafel slope, reaction order and material-dependent activity are interrelated. PMID- 22064887 TI - A naturally occurring nanomaterial from the Sundew (Drosera) for tissue engineering. AB - In recent years advances have been made in the design of novel materials for tissue engineering through the use of polysaccharides. This study evaluated the ability of a naturally secreted polysaccharide adhesive from the Sundew (Drosera capensis) as a support for cell growth. The Sundew adhesive has several advantages including its high elasticity and antibiotic nature. By coating glass cover slips with the Sundew adhesive, a network of nanofibers was generated that was capable of promoting attachment and differentiation of a model neuronal cell line, PC-12. We also demonstrated the potential of this material for repairing bone and soft tissue injuries, by testing attachment of osteoblasts and endothelial cells. Finally, it was determined that the Sundew biomaterial was stable through testing by atomic force microscopy and prolonged cell growth. This work has proven the capabilities of using a nanomaterial derived from the Sundew adhesive for the purpose of tissue engineering. PMID- 22064889 TI - 5-Bromo-2-(4-fluoro-phen-yl)-3-phenyl-sulfinyl-1-benzofuran. AB - In the title compound, C(20)H(12)BrFO(2)S, the 4-fluoro-phenyl ring makes a dihedral angle of 2.63 (6) degrees with the mean plane of the benzofuran fragment. The dihedral angle between the phenyl ring and the mean plane of the benzofuran fragment is 84.60 (6) degrees . In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds, and slipped pi-pi inter-actions between the benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.719 (3) A, inter-planar distance = 3.000 (3) A and slippage = 1.520 (3) A]. PMID- 22064890 TI - Carbon nanotube composite coating of neural microelectrodes preferentially improves the multiunit signal-to-noise ratio. AB - Extracellular metal microelectrodes are widely used to record single neuron activity in vivo. However, their signal-to-noise ratio (SNR) is often far from optimal due to their high impedance value. It has been recently reported that carbon nanotube (CNT) coatings may decrease microelectrode impedance, thus improving their performance. To tease out the different contributions to SNR of CNT-coated microelectrodes we carried out impedance and noise spectroscopy measurements of platinum/tungsten microelectrodes coated with a polypyrrole-CNT composite. Neuronal signals were recorded in vivo from rat cortex by employing tetrodes with two recording sites coated with polypyrrole-CNT and the remaining two left untreated. We found that polypyrrole-CNT coating significantly reduced the microelectrode impedance at all neuronal signal frequencies (from 1 to 10 000 Hz) and induced a significant improvement of the SNR, up to fourfold on average, in the 150-1500 Hz frequency range, largely corresponding to the multiunit frequency band. An equivalent circuit, previously proposed for porous conducting polymer coatings, reproduced the impedance spectra of our coated electrodes but could not explain the frequency dependence of SNR improvement following polypyrrole-CNT coating. This implies that neither the neural signal amplitude, as recorded by a CNT-coated metal microelectrode, nor noise can be fully described by the equivalent circuit model we used here and suggests that a more detailed approach may be needed to better understand the signal propagation at the electrode-solution interface. Finally, the presence of significant noise components that are neither thermal nor electronic makes it difficult to establish a direct relationship between the actual electrode noise and the impedance spectra. PMID- 22064892 TI - (MU-2,2'-Bipyrimidine-kappaN,N:N,N)bis-[triaqua-(sulfato-kappaO)manganese(II)]. AB - The title complex, [Mn(2)(SO(4))(2)(C(8)H(6)N(4))(H(2)O)(6)], is the second monoclinic polymorph [De Munno et al. (1995 ?). Inorg. Chem.34, 408-411; Hong et al. (1996 ?). Polyhedron, 15, 447-452]. The asymmetric unit contains two crystallographically independent half-mol-ecules of the binuclear Mn(II) complex; an inversion centre is located at the centroid of each complex. The two Mn(II) atoms in each complex mol-ecules are bridged by a bis-chelating 2,2'-bipyrimidine (bpym) ligand and each Mn(II) atom is six-coordinated in a considerably distorted octa-hedral environment defined by two N atoms of the bridging bpym ligand and four O atoms from one sulfato anionic ligand and three water mol-ecules. In the crystal, the complex mol-ecules are linked by O-H?O hydrogen bonds between the water and sulfato ligands, forming a three-dimensional network. PMID- 22064893 TI - 1-(4-Bromo-phen-yl)-2-(phenyl-sulfon-yl)ethanone. AB - The overall conformation of the title mol-ecule, C(14)H(11)BrO(3)S, is L-shaped, as seen in the value of the dihedral angle formed between the terminal benzene rings of 75.44 (13) degrees . The presence of C-H?O inter-actions leads to the formation of linear supra-molecular chains along the a-axis direction in the crystal structure. These are connected into supra-molecular arrays in the ab plane via C-H?pi contacts. PMID- 22064894 TI - (E)-1-(Naphthalen-1-yl)-3-(1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-one. AB - In the title mol-ecule, C(22)H(16)N(2)O, the phenyl ring is twisted slightly with respect to the plane of the central pyrazole ring [dihedral angle = 14.8 (2) degrees ]; the central ring is connected to the naphthyl ring through a -CH=CH C(=O)- fragment, whose C=C double bond has an E configuration. The pyrazole ring and naphthalene ring system are twisted by 46.3 (1) degrees . Weak inter molecular C-H?O hydrogen bonds link the mol-ecules, forming supra-molecular chains running along the a axis. The crystal studied was a non-merohedral twin with a component ratio of 0.544 (2):0.456 (2). PMID- 22064895 TI - Ethyl 3-oxo-2,3-dihydro-1,2-benzothia-zole-2-carboxyl-ate. AB - The title compound, C(10)H(9)NO(3)S, was synthesized by the reaction of benzo[d]isothia-zol-3(2H)-one with ethyl carbonochloridate in toluol. The benzisothia-zolone ring system is approximately planar, with a maximum deviation from the mean plane of 0.020 (1) A for the N atom. PMID- 22064896 TI - Constitutional factors in male potency disorders. AB - Fifty five patients of sexual inadequacy were studied for libidunous strength and androgyny score. Androgyny score was compared with a normal male population. The results show that premature ejaculators and patients with secondary disorders have a high sex drive. Androgyny scores did not differentiate the patients from controls as well as different subgroup of potency disorders. Biiliac diameter of patients with erectile impotence was more than the patients with premature ejaculation. PMID- 22064897 TI - tert-Butyl N-[3-hy-droxy-1-phenyl-4-(pyrimidin-2-ylsulfan-yl)butan-2-yl]carbamate monohydrate. AB - In the title hydrate, C(19)H(25)N(3)O(3)S.H(2)O, the configuration at each chiral centre in the organic mol-ecule is S, with the hy-droxy and carbamate substituents being anti [O-C-C-N torsion angle = -179.3 (3) degrees ]. The thio pyrimidyl and carbamate residues lie to one side of the pseudo-mirror plane defined by the C(5)S backbone of the mol-ecule; this plane approximately bis-ects the benzene ring at the 1- and 4-C atoms. The dihedral angle formed between the terminal rings is 5.06 (18) degrees . In the crystal, supra-molecular tubes aligned along the b axis are found: these are sustained by a combination of O H?O, O-H?N and N-H?O hydrogen bonds. PMID- 22064898 TI - N,N-Dimethyl-3-oxo-3-(thio-phen-2-yl)propanaminium chloride. AB - In the title mol-ecular salt, C(9)H(14)NOS(+).Cl(-), the crystal packing is stabilized by weak inter-molecular N-H?Cl, C-H?Cl and C-H?pi inter-actions, which lead to the formation of a two-dimensional supra-molecular layer which stacks along the b axis. PMID- 22064899 TI - Dibromido(4,7-diazadecane-1,10-di-amine)-copper(II). AB - In the title compound, [CuBr(2)(C(8)H(22)N(4))], the Cu(II) atom is six coordinate forming a distorted octa-hedral complex and is bonded to two axial bromide anions and four equatorial nitro-gen donors. The equatorial Cu-N bond distances range from 2.005 (8) to 2.046 (8) A while the axial Cu-Br distances are 2.8616 (17) and 2.9402 (17) A, thus the six-coordinate Cu complex shows the usual Jahn-Teller distortion. All amine hydrogen atoms participate in either inter- or intra-molecular hydrogen bonding to the Br anions. PMID- 22064900 TI - catena-Poly[[dichloridomercury(II)]-MU-1,4-bis-[(pyridin-2-yl)meth-oxy]benzene kappaN:N']. AB - In the title compound, [HgCl(2)(C(18)H(16)N(2)O(2))](n), the Hg(II) atom is four coordinated in a distorted tetra-hedral environment defined by two Cl atoms and two N atoms from two 1,4-bis-(pyridin-2-ylmeth-oxy)benzene ligands. The ligand shows a non-coplanar conformation, in which the dihedral angles between the two terminal pyridine rings and the linking benzene ring are 7.275 (17) and 74.020 (14) degrees . The flexible ligands link the Hg(II) atoms into a chain running along [010], with an Hg?Hg separation of 10.335 (5) A, which is equal to the b axis. The chains are connected by C-H?O and C-H?Cl hydrogen bonds. PMID- 22064901 TI - No association between ACE polymorphism and risk of nasopharyngeal carcinoma. AB - Emerging evidence has shown that angiotensin I-converting enzyme (ACE) plays pivotal roles not only in the regulation of cardiovascular homeostasis but also in the process of tumorigenesis. A common ACE I/D polymorphism has been found to be functional, with the D allele displaying a higher plasma ACE level and ACE activity. The purpose of this study was to investigate whether the ACE I/D polymorphism was related to the risk of nasopharyngeal carcinoma (NPC). The study included 175 patients with NPC and 279 age- and sex-matched control subjects. The ACE I/D polymorphism was identified by a polymerase chain reaction analysis. No association was found between the ACE I/D polymorphism and risk of NPC (ID vs. II: odds ratio [OR] = 0.77, 95% confidence interval [CI] 0.51-1.17; DD vs. II: OR = 0.98, 95%CI 0.56-1.72, respectively). This finding indicates that the ACE I/D polymorphism may not play a role in susceptibility to NPC. Further studies are warranted to confirm this finding, especially in ethnically disparate populations. PMID- 22064902 TI - (Penta-fluoro-propionato-kappaO)tetra-kis-(trimethyl-phosphine oxide kappaO)copper(II) penta-fluoro-propionate. AB - The title compound, [Cu(C(3)F(5)O(2))(C(3)H(9)OP)(4)](C(3)F(5)O(2)), comprises a cationic Cu(II) complex and a disordered penta-fluoro-propionate counter-ion. The metal atom has a distorted square-pyramidal coordination environment formed by four O atoms originating from trimethyl-phosphine oxide mol-ecules and the remaining one belonging to the monodentate penta-fluoro-propionate anion, which is situated in the basal plane of the pyramid. The mol-ecules are held together in the crystal by a net of weak C-H?O and C-H?F hydrogen bonds. The counter anion is disordered over two sets of sites in a 0.629 (5):0.371 (5) ratio. PMID- 22064903 TI - 1-Benzoyl-3-[3-cyano-8-methyl-4-(1-methyl-1H-pyrrol-2-yl)-5,6,7,8-tetra-hydro quinolin-2-yl]thio-urea. AB - In the N-substituted benzoyl-thio-urea, C(24)H(23)N(5)OS, the benzoyl-thio-urea unit is non-planar (r.m.s. deviation = 0.126 A). The aliphatic part of the tetra hydro-quinoline fused-ring system is disordered over two positions in a 0.592 (5):0.408 (5) ratio. The pyridine and pyrrole rings are twisted by 55.2 (1) degrees in order to avoid crowding of their respective substituents. Pairs of mol-ecules are linked by N-H?N hydrogen bonds, forming centrosymmetric dimers. Furthermore, an intra-molecular N-H?O hydrogen bond stabilizes the mol-ecular conformation. PMID- 22064904 TI - Time budget-, behavioral synchrony- and body score development of a newly released Przewalski's horse group Equus ferus przewalskii, in the Great Gobi B Strictly Protected Area in SW Mongolia. AB - The Przewalski's horse (Equus ferus przewalskii) became extinct in the wild in the 1960s, but survived as a species due to captive breeding. There have been several initiatives to re-introduce the species in central Asia, but until now only two projects in Mongolia establish free-ranging populations. Data on basic ecology and behavior of the species prior to extinction is largely lacking and a good documentation of the re-introduction process is essential. Between 13 May and 2 September 2003 we documented the time budget-, group synchrony and body score development of a newly released Przewalski's horse group in the Gobi area of SW Mongolia.Contrary to our expectations, the newly released Przewalski's horses did not show the expected succession of an exploration-, acclimatization-, and established phase. Grazing activity was very high after the release, decreased to a minimum in July and increased again towards the end of the study in September. Resting activity followed the opposite trend, whereas moving activity was more or less constant over the entire observation period. Behavioral synchronization of the group was high throughout the study period and immigration or emigration of members did not result in a de-synchronization of the group. The body score index never dropped, but rather increased for all group members.Our data suggests that captive bred Przewalski's horses experience little behavioral and nutritional stress when being released into the desert steppe of the Gobi regions after one year in an adaptation enclosure. PMID- 22064905 TI - Bromidotetra-kis-(2-isopropyl-1H-imidazole-kappaN)copper(II) bromide. AB - The Cu(II) atom in the title salt, [CuBr(C(6)H(10)N(2))(4)]Br, is coordinated in a square-pyramidal geometry by four imidazole N atoms and one bromide anion that is located at the apex of the pyramid. The cations and the anions form a two dimensional network parallel to (001) through N-H?Br hydrogen bonds. PMID- 22064906 TI - 2-[3-(1H-Benzimidazol-2-yl)prop-yl]-1-decyl-1H-benzimidazole. AB - The asymmetric unit of the title compound, C(27)H(36)N(4), contains two independent mol-ecules. Except for the atoms of the decyl chain, the non-H atoms of each mol-ecule are approximately coplanar (r.m.s. deviations = 0.075 and 0.164 A) and the -CH(2)CH(2)CH(2)- link connecting the two benzimidazolyl fused-ring systems is slightly opened up at the middle C atom. The decyl substituent adopts an extended zigzag conformation in both mol-ecules. In the crystal, adjacent mol ecules inter-act by N-H?N hydrogen bonds, generating a chain parallel to the c axis. PMID- 22064907 TI - 3-Benzyl-2-(furan-2-yl)-1,3-thia-zolidin-4-one. AB - In the title compound, C(14)H(13)NO(2)S, the thia-zolidine ring is approximately planar with a maximum deviation of 0.112 (1) A. The furan ring is disordered over two orientations, with an occupancy ratio of 0.901 (5):0.099 (5). The central thia-zolidine ring makes dihedral angles of 85.43 (8), 87.50 (11) and 87.9 (9) degrees with the phenyl ring and the major and minor components of the disordered furan ring, respectively. In the crystal, mol-ecules are connected by weak inter-molecular C-H?O hydrogen bonds, forming supra-molecular chains parallel to the b axis. PMID- 22064908 TI - 2,4-Diiodo-6-{[4-(morpholin-4-yl)phenyl]iminomethyl}phenol. AB - In the title compound, C(17)H(16)I(2)N(2)O(2), the two aromatic rings are almost coplanar [dihedral angle 2.57 (15) degrees ]. The morpholine ring adopts a chair conformation. The mol-ecular structure is stabilized by an O-H?N hydrogen bond and the crystal packing exhibits weak inter-molecular C-H?O and pi-pi [centroid to-centroid distances 3.663 (3)-4.073 (3) A] inter-actions. PMID- 22064909 TI - Saccades and smooth pursuit eye movements in central vertigo. AB - In order to analyze the diagnostic efficiency of saccadic and pursuit eye movements compared to findings from brain magnetic resonance imaging in patients with central vertigo, 108 patients were selected from 580 dizzy patients as cases of suspected central origin; the saccadic and pursuit eye movements were evaluated by electronystagmography and findings were compared to information from magnetic resonance imaging. The study of oculomotor movements in patients suspected of having a central lesion revealed a 83.3% sensitivity and 21.2% specificity. Restricting consideration to severe alterations in eye movements as indicative of a central origin, this test gives a 71.4% sensitivity and 50.0% specificity. In conclusion, the study of alterations in oculomotor movements, in patients with suspected central lesions, proved to be a test with good sensitivity also compared with results of magnetic resonance imaging. PMID- 22064910 TI - A non-parametric method for automatic neural spike clustering based on the non uniform distribution of the data. AB - In this paper, we propose a simple and straightforward algorithm for neural spike sorting. The algorithm is based on the observation that the distribution of a neural signal largely deviates from the uniform distribution and is rather unimodal. The detected spikes to be sorted are first processed with some feature extraction technique, such as PCA, and then represented in a space with reduced dimension by keeping only a few most important features. The resulting space is next filtered in order to emphasis the differences between the centers and the borders of the clusters. Using some prior knowledge on the lowest level activity of a neuron, such as e.g. the minimal firing rate, we find the number of clusters and the center of each cluster. The spikes are then sorted using a simple greedy algorithm which grabs the nearest neighbors. We have tested the proposed algorithm on real extracellular recordings and used the simultaneous intracellular recordings to verify the results of the sorting. The results suggest that the algorithm is robust and reliable and it compares favorably with the state-of-the-art approaches. The proposed algorithm tends to be conservative, it is simple to implement and is thus suitable for both research and clinical applications as an interesting alternative to the more sophisticated approaches. PMID- 22064911 TI - (Z)-Methyl 2-bromo-methyl-3-(2-chloro-phen-yl)acrylate. AB - In the title compound, C(11)H(10)BrClO(2), the dihedral angle between the benzene ring and the plane of the acrylate unit is 62.1 (1) degrees . The crystal packing is stabilzed by inter-molecular C-H?O hydrogen bonds and C-Cl?pi inter-actions [Cl?centroid = 3.829 (1) A and C-Cl?centroid = 165.3 (1) degrees ]. PMID- 22064912 TI - Poly[[tetra-aquatetrakis-[MU(3)-5-(pyridine-4-carboxamido) isophthalato]cobalt(II)digadolinium(III)] tetra-hydrate]. AB - In the centrosymmetric polymeric title compound, {[CoGd(2)(C(14)H(8)N(2)O(5))(4)(H(2)O)(4)].4H(2)O}(n), the Gd(III) cation is coordinated by one water mol-ecule and four pyridine-4-carboxamido-isophthalate (L) anions in a distorted square-anti-prismatic arrangement, while the Co(II) cation, located on an inversion center, is coordinated by two pyridyl-N atoms, two carboxyl-ate-O atoms and two water mol-ecules in a distorted octa-hedral geometry. The asymmetric unit contains two anionic L ligands: one bridges two Gd cations and one Co cation through two carboxyl groups and one pyridine-N atom; the other bridges two Gd cations and one Co cation through two carboxyl groups and the uncoordinated pyridine-N atom is hydrogen-bonded to the adjacent coordinated water mol-ecule. Extensive O-H?O and N-H?O hydrogen bonds are present in the crystal structure. PMID- 22064913 TI - Diaqua-dichloridobis(pyridine-kappaN)manganese(II). AB - The molecular title compound, [MnCl(2)(C(5)H(5)N)(2)(H(2)O)(2)], lies about an inversion centre. The Mn(II) atom is in an all-trans octa-hedral environment defined by two water mol-ecules, two chloride anions and two pyridine ligands. An inter-molecular hydrogen-bonding inter-action between a water mol-ecule and a chloride anion bonded to an adjacent Mn(II) atom generates an eight-membered ring. The crystal packing exhibits two inter-molecular pi-pi stacking inter actions between the aromatic rings, with centroid-centroid distances of 3.485 (12) and 3.532 (12) A. PMID- 22064914 TI - Cationic intermediates in oxidative addition reactions of Cl2 to [PtCl2(cis-1,4 DACH)]. AB - Oxidative addition and reductive elimination are fundamental processes in transition-metal chemistry. New interest in this field has been generated by the exploitation of platinum(IV) complexes as antitumor drugs. The two extra ligands can be used to render these species more resistant to attack by biological nucleophiles compared to their platinum(II) counterparts, to anchor additional pharmacologically active moieties, or, finally, to target the drug to specific sites by conferring responsiveness to some type of chemotaxis. On the other hand, platinum(IV) species are considered to be prodrugs and to require reduction to Pt(II) to become active. Thus, reductive elimination promoted by biological reducing agents becomes an important issue and it too could be exploited for targeting purposes. In this paper, we investigated the oxidation step in more detail and shown that, independent of the solvent used, a solvent molecule assists the reaction by entering in a trans position with respect to the attacking oxidant. In the case of bifunctional solvent molecules, such as dimethylsulfoxide, both S- and O-coordinated species are formed, the latter being thermodynamically favored. The substitution of the axially coordinated solvent molecule by a free chloride ion is found to be quite slow in organic solvents, as well as in water. It is also shown that the intermediate solvato-species can be exploited for binding just one molecule of another substrate in the axial position. PMID- 22064915 TI - Application of PARAFAC to a two-component system exhibiting fluorescence resonance energy transfer: from theoretical prediction to experimental validation. AB - One of the conventionally accepted requirements for parallel factor analysis (PARAFAC) to handle the fluorescence excitation emission matrices (EEMs) is the independence of each component's absorption and emission spectra in simple mixtures of fluorophores. EEMs of samples in which Forster resonance energy transfer (FRET) occurs between fluorophores seem to fail to meet this requirement. A rigorous theoretical treatment of the steady-state kinetics in the present work indicates that the fluorescence in the presence of FRET, excited by relatively weak excitation light intensity, can be reasonably separated into additive contributions from three parts: donors, acceptors and FRET. This prediction is for the first time verified experimentally in sodium dodecyl sulfate micellar solutions containing biphenyl as the energy donor and 2,5 diphenyloxazole as the energy acceptor. The experimental EEMs were well fitted to three components as predicted. A well accepted diagnostic test called core consistency (CC), specifically designed for modeling simple mixtures of fluorophores with PARAFAC, was found to be negative for the 3-component model in the present study. The simultaneous occurrence of good model fit and significantly negative CC when modeling fluorophore mixtures by conventional PARAFAC would be indicative of the presence of physical/chemical processes (e.g., FRET) that deviate from the conventional working requirements for PARAFAC. The extent of FRET has been independently measured or calculated by three methods: 1) decrease in steady state fluorescence of donor; 2) lifetime measurements with population analysis; and 3) Poisson statistics based on PARAFAC-determined distribution constants. The results of the three methods are consistent. The normalized scores of the three components found by PARAFAC also agree to within a few percent with relative concentrations in aqueous and micelle phases determined from distribution constants for the solutions prepared with nine different combinations of total donor and acceptor concentrations. Our theoretical treatment also for the first time spells out in detail the relationship between the PARAFAC scores and concentrations of components, in terms of photophysical constants of the components and spectral shape factors. PMID- 22064916 TI - The promise of standardized data collection: school health variables identified by states. AB - A gap in data prevents measurement of the needs of school-age children and the influence of school nursing interventions on student health and education outcomes. Its remedy is in the data collected in school health rooms. A national clinical database describing school health will allow education and health leaders to build evidence-based programs for children. Several states collect school health data describing student needs and school nursing practice. This study identified, collated, described, and evaluated the variables compiled from state school health reporting documents to identify commonalities and form the foundation of a standardized school health reporting system. A comprehensive content analysis of variables in the instruments yielded a framework within which school health data can be organized and described. It consists of five broad categories describing staffing; risk management; health promotion; episodic care; and care coordination. The result provides a nationally standardized coding set to describe school health. PMID- 22064917 TI - Aminobenzoates as building blocks for natural product assembly lines. AB - The ortho-, meta-, and para- regioisomers of aminobenzoate are building blocks for a wide range of microbial natural products. Both the ortho-isomer (anthranilate) and PABA derive from the central shikimate pathway metabolite chorismate while the meta-isomer is not available by that route and starts from UDP-3-aminoglucose. PABA is largely funnelled into folate biosynthesis while anthranilate is the scaffold for biosynthetic elaboration into many natural heterocycles, most notably with its role in indole formation for tryptophan biosynthesis. Anthranilate is also converted to benzodiazepinones, fumiquinazolines, quinoxalines, phenoxazines, benzoxazolinates, quinolones, and phenazines, often with redox enzyme participation. The 5-hydroxy form of 3 aminobenzaote is the starter unit for ansa-bridged rifamycins, ansamitocins, and geldanamycins, whereas regioisomers 2-hydroxy, 4-hydroxy and 2,4-dihydroxy-3 aminobenzoate are key components of antimycin, grixazone, and platencin and platensimycin biosynthesis, respectively. The enzymatic mechanisms for generation of the aminobenzoate regioisomers and their subsequent utilization for diverse heterocycle and macrocycle construction are examined. PMID- 22064918 TI - Therapeutic potential of intravenously administered human mesenchymal stromal cells. AB - Mesenchymal stem cells (MSC) represent a stem and progenitor cell population that has been shown to promote tissue recovery in pre-clinical and clinical studies. The study of MSC migration following systemic infusion of exogenous MSC is difficult. The challenges facing these efforts are due to a number of factors, including defining culture conditions for MSC, the phenotype of cultured MSC, the differences observed between cultured MSC and freshly isolated MSC. However, even if, MSC populations consist of a mixture of stem and more committed multipotent progenitors, it remains probable that these cell populations are still useful in the clinic as discussed in this review. PMID- 22064920 TI - New cadmium thio- and selenocyanato coordination compounds: structural snapshots on the reaction pathway to more condensed anionic networks. AB - In this contribution several new coordination compounds on the basis of cadmium(II) thio- and selenocyanate with pyrimidine as co-ligand were prepared and investigated for their structural, thermal and spectroscopic properties. The reaction of cadmium(II) thiocyanate with pyrimidine leads to the formation of four compounds, which from a structural point of view are closely related. In the most pyrimidine-rich 1 : 2 compound [Cd(NCS)(2)(pyrimidine)(2)](n) (1A) (1 : 2 = ratio between metal salt and the co-ligand pyrimidine) the Cd cations are linked by the pyrimidine ligands into layers and are additionally coordinated by two terminal N-bonded anions. In the 2 : 3 compound {[Cd(NCS)(2)](2)(pyrimidine)(3)}(n) (1B) the Cd cations are linked into chains by MU-1,3 bridging thiocyanato anions, which are connected into layers by only half of the pyrimidine ligands, whereas the other co-ligands are only terminal coordinated. Further reduction of the pyrimidine content leads to the formation of the 1 : 1 2D compound [Cd(NCS)(2)(pyrimidine)](n) (1CI) in which the terminal N-bonded thiocyanato anions become bridging. Surprisingly, crystallization experiments lead to the formation of an additional pyrimidine-deficient intermediate of composition {[Cd(NCS)(2)](3)(pyrimidine)(2)}(n) (1D), in which some of the MU-1,3 coordinated anions transform into MU-1,1,3 bridging thiocyanato anions. Consequently the four structures can be used as snapshots of intermediates on the way to a more condensed thiocyanato coordination network. In contrast, with cadmium selenocyanate only two different compounds were obtained. The 1 : 2 compound [Cd(NCSe)(2)(pyrimidine)(2)](n) (2A) is not isotypic to 1A and shows a completely different coordination topology whereas the pyrimidine deficient 1 : 1 compound (2B) shows a more condensed network with MU-1,3 coordinating selenocyanato anions. On heating, the 1 : 2 compound 1A decomposes into Cd(NCS)(2)via a new polymorphic modification (1CII) as intermediate which is metastable, whereas the 1 : 2 selenocyanato compound 2A transforms into the 1 : 1 compound 2B on heating which cannot be obtained phase pure under these conditions. If faster heating rates are used, there are indications for the formation of a 3 : 2 compound, which is amorphous to X-rays. The results are compared with those obtained for related thio- and selenocyanato coordination polymers with pyridine, pyridazine and pyrazine as co-ligand. Moreover, their impact on the structures and thermal reactivity of analogous paramagnetic compounds is discussed in detail. Based on the structural data of compound 1D the unknown structures of two intermediates were determined, which are formed in the thermal decomposition reaction of the Mn and Fe thiocyanato pyrimidine coordination polymers, reported recently. PMID- 22064921 TI - 1,1'-(2,5-Dimethyl-thio-phene-3,4-di-yl)diethanone. AB - The title compound, C(10)H(12)O(2)S, crystallizes with four mol-ecules in the asymmetric unit. The main conformational difference between these mol-ecules is the orientation of the acetyl groups with respect to the ring. Whereas one acetyl group is only slightly twisted with respect to the thio-phene ring [C-C-C-O torsion angles = 165.7 (4), -164.6 (4), 164.3 (4) and -163.6 (4) degrees ], the other acetyl group is markly twisted out of the ring plane [C-C-C-O torsion angles = -61.2 (6), 61.3 (7), -59.7 (7) and 59.9 (6) degrees ]. In the crystal, mol-ecules are linked by weak C-H?O inter-actions into infinite chains along the c axis. PMID- 22064922 TI - 2-Chloro-N-[2-(2-fluoro-benzo-yl)-4-nitro-phen-yl]-N-methyl-acetamide. AB - The title compound, C(16)H(12)ClFN(2)O(4), crystallizes with two mol-ecules in the asymmetric unit in which the dihedral angles between the mean planes of the two benzene rings are 65.1 (7) and 65.6 (6) degrees . In each mol-ecule, the nitro group displays rotational disorder over two orientations in a 0.503 (11):0.497 (11) ratio and the Cl atom is disordered in a 0.432 (5):0.568 (5) ratio. In one mol-ecule, the F atoms is statistically disordered over two positions. The crystal packing features weak inter-molecular C-H?O and C-H?Cl inter-actions, which form a layered network. PMID- 22064923 TI - {MU-1,2-Bis[bis-(4-meth-oxy-phen-yl)phosphan-yl]-1,2-diethyl-hydrazine kappaP:P'}bis-[chloridogold(I)] tetra-hydro-furan disolvate. AB - The title compound, [Au(2)Cl(2)(C(32)H(38)N(2)O(4)P(2))].2C(4)H(8)O, is formed from a bidentate phosphine ligand complexed to two linear gold(I) nuclei [P-Au-Cl = 175.98 (3) degrees ]. The nuclei are 3.1414 (2) A apart. The mol-ecule exhibits a twofold symmetry axis. Stacks of the compound are formed through inter molecular C-H?Cl inter-actions, while the tetra-hydro-furan (THF) solvate is further attached to the stacks through weak C-H?O hydrogen bonding from the THF O atom to two separate H atoms on the complex. PMID- 22064924 TI - 2-(1H-1,3-Benzodiazol-2-ylsulfan-yl)-1-(4-chloro-phen-yl)ethanone. AB - The mol-ecule in the structure of the title compound, C(15)H(11)ClN(2)OS, displays two planar residues [r.m.s. deviation = 0.014 A for the benzimidazole residue, and the ketone group is co-planar with the benzene ring to which it is attached forming a O-C-C-C torsion angle of -173.18 (14) degrees ] linked at the S atom. The overall shape is based on a twisted V, the dihedral angle formed between the two planes being 82.4 (2) degrees . The amine-H atom is bifurcated, forming N-H?O and N-H?S hydrogen bonds leading to dimeric aggregates. These are linked into a supra-molecular chain along the c axis via C-H?pi hydrogen bonds. Chains form layers in the ab plane being connected along the c axis via weak pi pi inter-actions [3.9578 (8) A] formed between centrosymmetrically related chloro substituted benzene rings. PMID- 22064925 TI - (2E,4E)-N-Benzyl-2-cyano-5-phenyl-penta-2,4-dienamide. AB - In the title compound, C(19)H(16)N(2)O, the mol-ecule adopts an E configuration about the two C=C double bonds. The dihedral angle between the phenyl rings is 88.89 (8) degrees . In the crystal, mol-ecules are linked by inter-molecular N H?N and C-H?O hydrogen bonds into chains running parallel to [130]. PMID- 22064926 TI - Atomically thin layers of MoS2 via a two step thermal evaporation-exfoliation method. AB - Two dimensional molybdenum disulfide (MoS(2)) has recently become of interest to semiconductor and optic industries. However, the current methods for its synthesis require harsh environments that are not compatible with standard fabrication processes. We report on a facile synthesis method of layered MoS(2) using a thermal evaporation technique, which requires modest conditions. In this process, a mixture of MoS(2) and molybdenum dioxide (MoO(2)) is produced by evaporating sulfur powder and molybdenum trioxide (MoO(3)) nano-particles simultaneously. Further annealing in a sulfur-rich environment transforms majority of the excess MoO(2) into layered MoS(2). The deposited MoS(2) is then mechanically exfoliated into minimum resolvable atomically thin layers, which are characterized using micro-Raman spectroscopy and atomic force microscopy. Furthermore Raman spectroscopy is employed to determine the effect of electrochemical lithium ion exposure on atomically thin layers of MoS(2). PMID- 22064927 TI - 2-[(2-Chloro-benzyl-idene)amino]-4,5,6,7-tetra-hydro-1-benzothio-phene-3 carbonitrile. AB - In the title compound, C(16)H(13)ClN(2)S, the mean planes fitted through all non H atoms of the heterocyclic five-membered and the benzene rings are oriented at a dihedral angle of 5.19 (7) degrees . In the crystal, a weak C-H?pi inter-action occurs, along with weak pi-pi inter-actions [cenroid-centroid distance = 3.7698 (11) A]. PMID- 22064928 TI - Serum lithium levels with slow-release and conventional lithium carbonate preparation. AB - Eighteen physically healthy volunteers were given 1200 mg of standard and sustained-release preparations of lithium on two different occasions. Serum lithium levels were estimated at four hourly intervals and statistically analysed. The findings and the results have been discussed with particular reference to their implications for future research. PMID- 22064929 TI - catena-Poly[[tetra-kis-(hexa-methyl-phospho-ramide-kappaO)bis-(nitrato kappaO,O')samarium(III)] [silver(I)-di-MU-sulfido-tungstate(VI)-di-MU-sulfido]]. AB - The Sm atom in the cation of the title salt, {[Sm(NO(3))(2)(C(6)H(18)N(3)OP)(4)][AgS(4)W]}(n), is coordinated by eight O atoms derived from two chelating nitrate anions, and four hexamethylphos-phoramide ligand, defining a distorted square-antiprismatic geometry. The anions self assemble into polymeric chains via W-S-Ag bridges having a [AgS(4)W] repeat unit; the W-Ag-W and Ag-W-Ag angles are 161.657 (17) and 153.978 (9) degrees , respectively. The title complex is isostructural with the Y, Yb, Eu, Nd, La and Dy isomorphs. PMID- 22064930 TI - (E)-4-[2-(2-Hy-droxy-benzo-yl)-hydra-zin-ylidene]penta-noic acid. AB - The title mol-ecule, C(12)H(14)N(2)O(4), adopts a trans configuration with respect to the C=N double bond. The amino group is involved in an intra-molecular N-H?O hydrogen bond. In the crystal structure, inter-molecular O-H?O hydrogen bonds link the mol-ecules into doubled sheets parallel to the (101) plane. PMID- 22064931 TI - Spatial resolution of the pain system: a proximal-to-distal gradient of sensitivity revealed with psychophysical testing. AB - The spatial resolution of the pain system has not been studied in depth, and results are contradictory regarding the gradient of spatial resolution. Microneurographic recordings have revealed smaller receptive fields and higher density of nociceptors in more distal than proximal leg regions, whereas histological studies report higher density of C-fibers in more proximal than distal body regions. Due to this controversy, we conducted various psychophysical tests in order to examine the nociceptive spatial resolution and its gradient. Heat-pain threshold (HPT), perceived pain intensity, spatial summation (SS) of pain, two-point discrimination (2PD) of pain, and pain localization were measured in four body regions: upper back, thigh, lower leg, and foot. The highest HPT was demonstrated in the lower leg as compared with more proximal regions (P < 0.0001). SS was observed in all the regions and was found to be smallest in the foot (P < 0.05). The smallest 2PD and localization distances were found in the foot (P < 0.01) as compared with the lower leg and upper back. It appears that the nociceptive spatial resolution has a proximal-to-distal pattern of performance, namely that the spatial resolution of pain is finer in more distal than proximal body regions, similar to that of the touch system. PMID- 22064932 TI - Sound can improve visual search in developmental dyslexia. AB - We examined whether developmental dyslexic adults suffer from sluggish attentional shifting (SAS; Hari and Renvall in Trends Cogn Sci 5:525-532, 2001) by measuring their shifting of attention in a visual search task with dynamic cluttered displays (Van der Burg et al. in J Exp Psychol Human 34:1053-1065, 2008). Dyslexics were generally slower than normal readers in searching a horizontal or vertical target among oblique distracters. However, the addition of a click sound presented in synchrony with a color change of the target drastically improved their performance up to the level of the normal readers. These results are in line with the idea that developmental dyslexics have specific problems in disengaging attention from the current fixation, and that the phasic alerting by a sound can compensate for this deficit. PMID- 22064933 TI - 2,4-Dichloro-N-(2,5-dimethyl-phen-yl)benzene-sulfonamide. AB - The asymmetric unit of the title compound, C(14)H(13)Cl(2)NO(2)S, contains three independent moleules. The torsion angles of the C-SO2-NH-C segments in the three mol-ecules are 67.5 (2), 83.4 (2) and -77.5 (2) degrees . The two aromatic rings are tilted relative to each other by 68.8 (1), 64.1 (1) and 68.5 (1) degrees . The crystal structure features dimers linked by pairs of N-H?O hydrogen bonds. PMID- 22064934 TI - catena-Poly[[triphenyl-tin(IV)]-MU-5-amino-2-nitro-benzoato-kappaO:O]. AB - The title compound, [Sn(C(6)H(5))(3)(C(7)H(5)N(2)O(4))](n), forms polymeric chains along [010]. The Sn(IV) ion is five-coordinated in a distorted trigonal bipyramidal geometry by two monodentate carboxyl-ate groups and three phenyl rings. The axial sites are occupied by the O atoms of two symmetry-related carboxyl-ate groups [O-Sn-O = 170.88 (3) degrees ]. The benzene ring of the 5 amino-2-nitro-benzoate ligand forms dihedral angles of 82.92 (6), 81.10 (6) and 83.54 (6) degrees with respect to the three phenyl rings. In the crystal, the chains are linked by inter-molecular N-H?O and weak C-H?O inter-actions into a three-dimensional network. The crystal structure is further stabilized by weak inter-molecular C-H?pi inter-actions. PMID- 22064935 TI - 1'-Methyl-4'-phenyldispiro-[indan-2,2'-pyrrolidine-3',2''-indan]-1,3,1''-trione. AB - The conformation of the title compound, C(27)H(21)NO(3), is stabilized by a weak intra-molecular C-H?O hydrogen bond, which generates an S(6) ring motif. The pyrrolidine ring adopts a half-chair conformation. Both of the other five membered rings are in envelope conformations. No significant inter-molecular hydrogen bonds are observed. PMID- 22064936 TI - N-{(2S)-3-Hy-droxy-4-[(5-methyl-1,3,4-thia-diazol-2-yl)sulfan-yl]-1-phenyl-2-but yl}-4-methyl-benzene-sulfonamide. AB - The thia-diazoyl and sulfonyl-benzene rings in the title compound, C(20)H(23)N(3)O(3)S(3), are aligned to the same side of the mol-ecule, forming a twisted 'U' shape [dihedral angle = 77.6 (5) degrees ]. The benzyl-benzene ring is orientated in the opposite direction from the mol-ecule but projects approximately along the same axis as the other rings [dihedral angle between benzene rings = 28.2 (5) degrees ] so that, overall, the mol-ecule has a flattened shape. The hy-droxy and amine groups are almost syn which enables the formation of inter-molecular hy-droxy-OH?N(thia-diazo-yl) and amine-H?O(sulfon yl) hydrogen bonds leading to a supra-molecular chain aligned along the a axis. PMID- 22064937 TI - Stepwise synthesis of a hydrido, N-heterocyclic dicarbene iridium(III) pincer complex featuring mixed NHC/abnormal NHC ligands. AB - We describe a stepwise synthesis of the hydrido, N-heterocyclic dicarbene iridium(III) pincer complex [Ir(H)I(C(NHC)CC(aNHC))(NCMe)] (3) which features a combination of normal and abnormal NHC ligands. The reaction of the bis(imidazolium) diiodide [(CH(imid)CHCH(imid))]I(2) (1) with [Ir(MU-Cl)(cod)](2) afforded first the mono-NHC Ir(I) complex [IrI(cod)(CH(imid)CHC(NHC))]I (2), which was then reacted with 2 equiv. of Cs(2)CO(3) in acetonitrile at 60 degrees C for 40 h to yield 3. These observations support our previously proposed mechanism for the formation of hydrido, N-heterocyclic dicarbene iridium(III) pincer complexes from the reaction of bis(imidazolium) salts with weak bases involving a mono-NHC Ir(I) intermediate. We describe the reactivity of the mono NHC Ir(I) complex 2 under various conditions. By changing the reaction solvent from MeCN to toluene, we observed the cleavage of the imidazol-2-ylidene ring and the formation of an iminoformamide-containing mono-NHC Ir(I) complex [IrI(cod){[NHCH=CHN(Ad)CHO]CHC(NHC)}] (4). Complex 4 was also prepared in high yield from the reaction of 2 with strong bases (potassium tert-butoxide or potassium hexamethyldisilazane), via the initial formation of the complex [IrI(cod)(CH(NHC)CHC(NHC))] (5), which contains a coordinated NHC moiety and a free carbene arm, followed by subsequent hydrolysis of the latter. The bis(imidazolium) salt 1 can be deprotonated by strong bases to form the bis(carbene) ligand C(NHC)CHC(NHC) (6), which readily reacts with [Ir(MU Cl)(cod)](2) to give the dinuclear complex [{IrI(cod)}(2)(MU-C(NHC)CHC(NHC))] (7), in which the N-heterocyclic bis(carbene) ligand bridges the two metals through the carbene carbon atoms. PMID- 22064938 TI - catena-Poly[(diaqua-strontium)-bis-(MU-2-methyl-3,5-dinitro-benzoato)]. AB - The title compound, [Sr(C(8)H(5)N(2)O(6))(2)(H(2)O)(2)](n), essentially consists of a one-dimensional polymeric network with Sr(2)O(2) rings extending along the [100] direction. The range of Sr-O bond lengths is 2.4822 (13)-2.8113 (13) A. C H?O and O-H?O hydrogen-bonding inter-actions stabilize the mol-ecules in the form of a two-dimensional polymeric network parallel to (001). One of the nitro groups is disordered over three sets of sites with the occupancy ratio of 0.46:0.32:0.22. PMID- 22064939 TI - N-(4-Chloro-phenyl-sulfon-yl)-2-methyl-propanamide. AB - In the crystal structure of the title compound, C(10)H(12)ClNO(3)S, the N-C bond in the C-SO(2)-NH-C segment has a gauche torsion with respect to the S=O bonds. The mol-ecule is twisted at the S atom with a C-S-N-C torsion angle of -62.3 (3) degrees . The benzene ring and the SO(2)-NH-CO-C segment form a dihedral angle of 89.3 (1) degrees . In the crystal, mol-ecules are linked by pairs of N-H?O hydrogen bonds into inversion dimers. PMID- 22064940 TI - Multiple depositions of Ag nanoparticles on chemically modified agarose films for surface-enhanced Raman spectroscopy. AB - A facile and cost-effective approach for the preparation of a surface-enhanced Raman spectroscopy (SERS) substrate through constructing silver nanoparticle/3 aminopropyltriethoxysilane/agarose films (Ag NPs/APTES/Agar film) on various solid supports is described. The SERS performance of the substrate was systematically investigated, revealing a maximum SERS intensity with four layers of the Ag NP deposition. The enhancement factor of the developed substrate was calculated as 1.5 * 10(7) using rhodamine 6G (R6G) as the probe molecule, and the reproducibility of the SERS signals was established. A high throughput screening platform was designed, manufactured and implemented which utilised the ability to cast agarose to assemble arrays. Quantitative analysis of 4-aminobenzoic acid (4 ABA) and 4-aminothiophenol (4-ATP) was achieved over a ~0.5 nM-0.1 MUM range. PMID- 22064941 TI - Purines and the Anti-Epileptic Actions of Ketogenic Diets. AB - Ketogenic diets are high in fat and low in carbohydrates and represent a well established and effective treatment alternative to anti-epileptic drugs. Ketogenic diets are used for the management of a variety of difficult-to-treat or intractable seizure disorders, especially pediatric refractory epilepsy. However, it has been shown that this dietary therapy can reduce seizures in people of all ages, and ketogenic diets are being applied to other prevalent medical conditions such as diabetes. Although used effectively to treat epilepsy for nearly 90 years, the mechanism(s) by which ketogenic diets work to reduce seizures remain ill-understood. One mechanism receiving increased attention is based on findings that ketogenic diets increase the brain energy molecule ATP, and may also increase the levels and actions of the related endogenous inhibitory neuromodulator adenosine. ATP and adenosine have both been identified as important modulators of seizures; seizures increase the actions of these purines, these purines regulate epileptic activity in brain, adenosine receptor antagonists are pro-convulsant, and adenosinergic mechanisms have been implicated previously in the actions of approved anti-epileptic therapeutics. Here we will review recent literature and describe findings that shed light on mechanistic relationships between ketogenic diets and the purines ATP and adenosine. These emerging mechanisms hold great promise for the effective therapeutic management of epileptic seizures and other neurological conditions. PMID- 22064942 TI - N-(4-Chloro-1,3-benzothia-zol-2-yl)-2-(3-methyl-phen-yl)acetamide monohydrate. AB - In the title compound, C(16)H(13)ClN(2)OS.H(2)O, the dihedral angle between the mean planes of the benzothia-zole ring system and the methylphenyl ring is 79.3 (6) degrees . The crystal packing features inter-molecular O-H?N, O-H?O and N-H?O hydrogen bonds involving the water mol-ecule and weak C-H?O, C-H?Cg and pi-pi stacking inter-actions [centroid-centroid distances = 3.8743 (7), 3.7229 (7) and 3.7076 (8) A]. PMID- 22064943 TI - Effects of temperature and soil moisture on methyl halide and chloroform fluxes from drained peatland pasture soils. AB - A series of laboratory-based incubations using a stable isotope tracer technique was applied to measure the net and gross fluxes of CH(3)Cl and CH(3)Br as well as the net fluxes of CHCl(3) from surface soils of the Sacramento-San Joaquin Delta of California. Annually averaged flux measurements show that these mineral/oxidized peat soils are a net source of CH(3)Cl (140 +/- 266 nmol m(-2) d(-1)) and CHCl(3) (258 +/- 288 nmol m(-2) d(-1)), and a net sink of CH(3)Br ( 2.3 +/- 4.5 nmol m(-2) d(-1)). Gross CH(3)Cl and CH(3)Br fluxes are strongly influenced by both soil moisture and temperature: gross production rates of CH(3)Cl and CH(3)Br are linearly correlated with temperature, whereas gross consumption rates exhibit Gaussian relationships with maximum consumption at soil moisture levels between 20 and 30% volumetric water content (VWC) and a temperature range of 25 to 35 degrees C. Although soil moisture and soil temperature strongly affect consumption rates, the range of gross consumption rates overall is limited (-506 +/- 176 nmol m(-2) d(-1) for CH(3)Cl and -12 +/- 4 nmol m(-2) d(-1) for CH(3)Br) and is similar to rates reported in previous studies. CHCl(3) fluxes are not correlated with methyl halide fluxes, temperature, or soil moisture. The annual emission rates of CHCl(3) from the Sacramento-San Joaquin Delta are found to be a potentially significant local source of this compound. PMID- 22064944 TI - Mechanism and determinants of nanoparticle penetration through human skin. AB - The ability of nanoparticles to penetrate the stratum corneum was the focus of several studies. Yet, there are controversial issues available for particle penetration due to different experimental setups. Meanwhile, there is little known about the mechanism and determinants of their penetration. In this paper the penetration of four model gold nanoparticles of diameter 6 and 15 nm, differing in surface polarity and the nature of the vehicle, through human skin was studied using multiphoton microscopy. This is in an attempt to profoundly investigate the parameters governing particle penetration through human skin. Our results imply that nanoparticles at this size range permeate the stratum corneum in a similar manner to drug molecules, mainly through the intercellular pathways. However, due to their particulate nature, permeation is also dependent on the complex microstructure of the stratum corneum with its tortuous aqueous and lipidic channels, as shown from our experiments performed using skin of different grades of barrier integrity. The vehicle (toluene-versus-water) had a minimal effect on skin penetration of gold nanoparticles. Other considerations in setting up a penetration experiment for nanoparticles were also studied. The results obtained are important for designing a new transdermal carrier and for a basic understanding of skin-nanoparticle interaction. PMID- 22064945 TI - Polyaspartic acid coated manganese oxide nanoparticles for efficient liver MRI. AB - We report in this communication a simple, facile surface modification strategy to transfer hydrophobic manganese oxide nanoparticles (MONPs) into water by using polyaspartic acid (PASP). We systematically investigated the effect of the size of PASP-MONPs on MRI of normal liver and found that the particles with a core size of 10 nm exhibited greater enhancement than those with larger core sizes. PMID- 22064946 TI - Subcutaneous sarcoidosis: a rare involvement of the paralateral nasal region. AB - A case of subcutaneous sarcoidosis involving the paralateral nasal region is described and a brief review of the literature is made. Subcutaneous sarcoidosis without systemic disease is a rare entity and has seldom been reported on the trunk and face. Diagnosis is always difficult as it can only be confirmed by histological studies. PMID- 22064947 TI - A new method of UV-patternable hydrophobization of micro- and nanofluidic networks. AB - This work reports a new method to hydrophobize glass-based micro- and nanofluidic networks. Conventional methods of hydrophobizing glass surfaces often create particulate debris causing clogging especially in shallow nanochannels or require skilful handling. Our novel method employs oxygen plasma, silicone oil and ultraviolet (UV) light. The contact angle of the modified bare glass surface can reach 100 degrees whilst the inner channels after treatment facilitate stable and durable water-in-oil droplet generation. This modified surface was found to be stable for more than three weeks. The use of UV in principle enables in channel hydrophobic patterning. PMID- 22064948 TI - (S)-N-{1-[5-(4-Chloro-benzyl-sulfanyl)-1,3,4-oxadiazol-2-yl]eth-yl}-4-methyl benzene-sulfonamide. AB - The title compound, C(18)H(18)ClN(3)O(3)S(2), adopts by folding the form of a distorted disc. Inter-planar angles are 29.51 (7) and 63.43 (7) degrees from the five-membered ring to the aromatic systems and 34.80 (6) degrees between these two latter rings. The absolute configuration was confirmed by determination of the Flack parameter. In the crystal, the mol-ecules are linked by four hydrogen bonds, one classical (N-H?N) and three 'weak' (C-H?O), forming layers parallel to the ac plane; these are in turn linked in the third dimension by Cl?N [3.1689 (16) A] and Cl?O [3.3148 (13) A] contacts to the heterocyclic ring. PMID- 22064949 TI - Increasing access to learning for the adult basic education learner with learning disabilities: evidence-based accommodation research. AB - Accommodating adult basic education (ABE) learners with learning disabilities (LD) is common practice across many instructional, testing, and work settings. However, the results from this literature search indicate that very few empirically based studies are available to support or reject the effectiveness of a great deal of accommodation implementation. In addition, in light of the profound changes to literacy taking place in today's digital, networked, and multimodal world, technology is redefining traditional concepts of accessibility and accommodation. PMID- 22064950 TI - The impact of learning disabilities on adulthood: a review of the evidenced-based literature for research and practice in adult education. AB - It is now well established that learning disabilities (LD) persist into the adult years, yet despite a developing literature base in this area, there is a paucity of evidence-based research to guide research and practice. Consistent with the demands of the adult stage of development, autonomy and self-determination are crucial to quality-of-life issues to adults in general, and specifically to adults with LD. There are many areas of functioning in which adults need to adapt successfully, such as employment, family, social and emotional, daily living routines, community, and recreation and leisure. In essence, there are a myriad of challenges and outcomes as adults navigate the trials and tribulations of LD as it manifests itself into adulthood. This review of the extant evidence-based literature seeks to discover relevant knowledge that can be shared with practitioners who serve adults with LD in a variety of professional and volunteer roles, particularly in adult education settings. PMID- 22064951 TI - Effective literacy instruction for adults with specific learning disabilities: implications for adult educators. AB - Adults with learning disabilities (LD) attending adult basic education, GED programs, or community colleges are among the lowest performers on measures of literacy. For example, on multiple measures of reading comprehension, adults with LD had a mean reading score at the third grade level, whereas adults without LD read at the fifth grade level. In addition, large numbers of adults perform at the lowest skill levels on quantitative tasks. Clearly, significant instructional challenges exist for adults who struggle with literacy issues, and those challenges can be greater for adults with LD. In this article, the literature on adults with LD is reviewed, and evidenced-based instructional practices that significantly narrow the literacy achievement gap for this population are identified. Primary attention is given to instructional factors that have been shown to affect literacy outcomes for adults with LD. These factors include the use of explicit instruction, instructional technology, and intensive tutoring in skills and strategies embedded in authentic contexts. PMID- 22064952 TI - Effects of a psychosocial intervention on the executive functioning in children with ADHD. AB - The purpose of this study was to analyze the effects of an intensive psychosocial intervention on the executive functioning (EF) in children with ADHD. The treatment was carried out in a coordinated manner over a period of 10 weeks with 27 children with ADHD aged 7 to 10, their parents, and their teachers. A battery of neuropsychological tasks was applied to evaluate attention, interference control, verbal and visuospatial working memory, planning ability, and flexibility. The comparative analysis of the treated group of ADHD children and an untreated ADHD group showed significant differences that were especially important in visuospatial memory and planning in favor of the treated children, even when the scores in the pretreatment phase were included as covariables. Likewise, improvements were observed in the parents' and teachers' behavioral ratings of hyperactivity or impulsivity and inattention. The conclusion was drawn that psychosocial interventions with children with ADHD can have a positive effect on some executive functions. PMID- 22064953 TI - In situ mechanical analysis of cardiomyocytes at nano scales. AB - Nanomechanical behaviors of single living cardiomyocytes are quantitatively observed using calculated torsions and deflections of an AFM cantilever. The lateral contractions are related to the calcium intensity within rather than the vertical beating power of the cardiomyocytes. Drug-induced nanomechanical changes of cardiomyocytes were further investigated by measuring lateral contractions in real time. PMID- 22064954 TI - Python erythrocytes are resistant to alpha-hemolysin from Escherichia coli. AB - alpha-Hemolysin (HlyA) from Escherichia coli lyses mammalian erythrocytes by creating nonselective cation pores in the membrane. Pore insertion triggers ATP release and subsequent P2X receptor and pannexin channel activation. Blockage of either P2X receptors or pannexin channels reduces HlyA-induced hemolysis. We found that erythrocytes from Python regius and Python molurus are remarkably resistant to HlyA-induced hemolysis compared to human and Trachemys scripta erythrocytes. HlyA concentrations that induced maximal hemolysis of human erythrocytes did not affect python erythrocytes, but increasing the HlyA concentration 40-fold did induce hemolysis. Python erythrocytes were more resistant to osmotic stress than human erythrocytes, but osmotic stress tolerance per se did not confer HlyA resistance. Erythrocytes from T. scripta, which showed higher osmotic resistance than python erythrocytes, were as susceptible to HlyA as human erythrocytes. Therefore, we tested whether python erythrocytes lack the purinergic signalling known to amplify HlyA-induced hemolysis in human erythrocytes. P. regius erythrocytes increased intracellular Ca2+ concentration and reduced cell volume when exposed to 3 mM ATP, indicating the presence of a P2X7-like receptor. In addition, scavenging extracellular ATP or blocking P2 receptors or pannexin channels reduced the HlyA-induced hemolysis. We tested whether the low HlyA sensitivity resulted from low affinity of HlyA to the python erythrocyte membrane. We found comparable incorporation of HlyA into human and python erythrocyte membranes. Taken together, the remarkable HlyA resistance of python erythrocytes was not explained by increased osmotic resistance, lack of purinergic hemolysis amplification, or differences in HlyA affinity. PMID- 22064955 TI - Sleep disturbances: time to join the top 10 potentially modifiable cardiovascular risk factors? PMID- 22064956 TI - Diversity of myocardial interstitial proteolytic pathways: gene deletion reveals unexpected consequences. PMID- 22064957 TI - Catheter-based reperfusion treatment of pulmonary embolism. PMID- 22064958 TI - Sex/gender differences in cardiovascular disease prevention: what a difference a decade makes. PMID- 22064959 TI - Longest survivor of pulmonary atresia with ventricular septal defect: well developed major aortopulmonary collateral arteries demonstrated by multidetector computed tomography. PMID- 22064960 TI - Constrictive pericarditis presenting as a large mediastinal mass causing functional tricuspid and pulmonary stenosis. PMID- 22064961 TI - Changes in stroke epidemiology, prevention, and treatment. PMID- 22064963 TI - Letter by Vorpahl and Kelm regarding article, "Stent thrombogenicity early in high-risk interventional settings is driven by stent design and deployment and protected by polymer-drug coatings". PMID- 22064964 TI - rac-Dichlorido(1-{(diphenyl-phosphan-yl)[2-(diphenyl-phosphan-yl)phen-yl]meth yl}ferrocene-kappaP,P')palladium(II) dimethyl sulfoxide disolvate. AB - The racemic title compound, [FePdCl(2)(C(5)H(5))(C(36)H(29)P(2))].2(CH(3))(2)SO, features a Pd-chelating 1,3-diphosphine, which is substituted at a P-bearing asymmetric C atom by a ferrocenyl group. The Pd(II) atom is in a distorted quadratic coordination by two P and two Cl atoms with bond lengths of 2.2414 (3) and 2.2438 (3) A for Pd-P, and 2.3452 (3) and 2.3565 (3) A for Pd-Cl. The conformation of the Pd complex is controlled by an intra-molecular slipped pi-pi stacking inter-action between a phenyl and a cyclo-penta-dienyl ring with corresponding C?C distances starting at 3.300 (2) A and the distance between ring centroids being 3.674 (2) A. The crystal structure is stabilized by C-H?Cl and C H?O hydrogen bonds. The (CH(3))(2)SO solvent mol-ecules are arranged in layers parallel to (101) and are linked in pairs by C-H?O inter-actions. One (CH(3))(2)SO mol-ecule is orientationally disordered [occupancy ratio 0.8766 (17):0.1234 (17)] with sulfur in two positions at both sides of its C(2)O triangle. PMID- 22064965 TI - 2-Methyl-propan-2-aminium 2-(meth-oxy-carbon-yl)benzoate. AB - In the title compound, C(4)H(12)N(+).C(9)H(7)O(4) (-), two C atoms and the N atom of the cation lie on a mirror plane, while all the atoms of the anion are disordered about a mirror plane. In the crystal, N-H?O hydrogen bonds link the components into chains along [010]. In the anion, the mean planes of the methoxycarbonyl and carboxylate groups form dihedral angles of 83.0 (2) and 83.2 (2) degrees , respectively, with the aromatic ring. PMID- 22064966 TI - The place for remodeling technique and stenting in the endovascular management of intracranial aneurysms: a single-center analysis from 2008 to 2010. AB - INTRODUCTION: The objective of this study was to analyze the place for the balloon remodeling and stenting in the endovascular treatment of intracranial aneurysms as well as the impact of their use on the failure and complications rates. Analysis was conducted in a recent 3-year period (2008-2010) in a single center. METHODS: A total of 287 aneurysms, harbored by 252 patients (age, 16-87 years; mean, 50.9 +/- 13.4 years), were proposed for endovascular treatment. Patient and aneurysms characteristics, modalities of treatment (coiling, remodeling, or stenting), failure rate, and rate of adverse events related to the treatment were analyzed. RESULTS: Treatment failed in 3/287 aneurysms (1.0%). The use of the remodeling technique and stenting increased over time (23.9% and 4.6% in 2008, 39.5% and 14.9% in 2009, and 43.9% and 20.7% in 2010, respectively). The remodeling technique was used in a similar percentage of cases independent of aneurysm characteristics (aneurysm status, location, and size, and neck size), except dome-to-neck ratio. Stenting was more frequently used in unruptured aneurysms, in internal carotid artery aneurysms, and in wide neck aneurysms. The rate of specific adverse events (thromboembolism and intraoperative rupture) was similar in coiling (2.8%), remodeling (6.9%), and stenting (1.1%). The rate of specific adverse events was similar in 2008, 2009, and 2010 (2.3%, 4.4%, and 6.1%, respectively). CONCLUSION: In the endovascular management of intracranial aneurysms, the large use of the remodeling technique combined with stenting in selected cases enables a low rate of treatment failures without increasing the rate of complications. PMID- 22064967 TI - Few-atomic-layered boron carbonitride nanosheets prepared by chemical vapor deposition. AB - Few-atomic-layered boron carbonitride (BCN) nanosheets have been grown on Si substrate by microwave plasma chemical vapor deposition from a gas mixture of CH(4)-N(2)-H(2)-BF(3). The grown BCN nanosheets are oriented with their base planes perpendicular to the substrate surface. Ultrathin BCN nanosheets with thickness from 2 to a few atomic layers account for a considerable portion of the products, although many of them have more than 10 layers. Photoluminescence is measured for the BCN nanosheets and intense emission at 3.27 eV with very weak defect-related emission is observed for the nanosheets with the composition of B(0.38)C(0.27)N(0.35). The present BCN nanosheets are promising for applications in nanoelectronics, catalyst supports, gas adsorption, etc. PMID- 22064968 TI - One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol. AB - Difluoroalkenylzinc reagents prepared from 1-(2'-methoxy-ethoxymethoxy)-2,2,2 trifluoroethane and 1-(N,N-diethylcarbamoyloxy)-2,2,2-trifluoroethane at ice bath temperatures underwent Negishi coupling with a range of aryl halides in a convenient one pot procedure. While significant differences between the enol acetal and carbamate reagents were revealed, the Negishi protocol compared very favourably with alternative coupling procedures in terms of overall yields from trifluoroethanol. PMID- 22064969 TI - 1-Heptyl-1,3,6,8-tetraaza-tricyclo-[4.3.1.1]undecan-1-ium iodide. AB - The title compound C(14)H(29)N(4) (+).I(-) salt, was obtained by the reaction of cage adamanzane-type aminal 1,3,6,8-tetra-aza-tricyclo-[4.3.1.1(3,8)]undecane with heptyl iodide. In the cation, the bond lengths and angles are within normal ranges, except for one N-C(ring) bond distance of 1.542 (3) A, which is unexpectedly long compared with related compounds. In the crystal, ions are linked through C-H?I hydrogen bonds. The crystal studied was a non-merohedral twin with a minor twin domain of 6.56 (5)%. PMID- 22064970 TI - The vitamin D receptor regulates rheumatoid arthritis synovial fibroblast invasion and morphology. AB - Serum levels of vitamin D levels are commonly reduced in patients with rheumatoid arthritis (RA) and have been implicated in disease pathogenesis. We recently identified a new vitamin D receptor transcriptional signature in synovial tissues from rats with mild and nonerosive arthritis, suggesting a vitamin D-mediated protective effect. In the present study, we address the hypothesis that part of the vitamin D protective effect is mediated via interference with fibroblast-like synoviocyte (FLS) invasive properties, an in vitro cellular phenotype that correlates with radiographic and histological damage in pristane-induced arthritis and RA. FLSs derived from DA rats with pristane-induced arthritis and RA patients were studied in an in vitro model of invasion through a collagen-rich barrier (Matrigel) over a 24-h period, in the presence or absence of calcitriol, an active form of vitamin D. Matrix metalloprotease (MMP) expression levels were analyzed with zymography and quantitative real-time polymerase chain reaction, and the cytoskeleton was studied with immunofluorescense microscopy. Calcitriol significantly inhibited DA and RA FLS invasion by 54% and 53%, respectively. Calcitriol also reduced interleukin (IL)-1beta-induced expression of MMP-1 by 95% in DA FLSs and by 73.5% in RA FLS. Calcitriol treatment reduced actin cytoskeleton reorganization, reduced polarized formation of lamellipodia and reduced colocalization of phosphorylated focal adhesion kinase (p-FAK) with lamellipodia, all consistent with reduced cell ability to move and invade. In conclusion, we identified a new effect of calcitriol in FLS invasion. This discovery suggests that the reduced serum levels of vitamin D and its metabolites commonly seen in RA might increase risk for FLS-mediated cartilage and bone invasion and erosions. Treatment with vitamin D or its analogs has the potential to become a helpful adjuvant aimed at preventing or reducing joint destruction. PMID- 22064971 TI - Oxidized low-density lipoprotein-dependent platelet-derived microvesicles trigger procoagulant effects and amplify oxidative stress. AB - The fundamental mechanisms that underlie platelet activation in atherothrombosis are still obscure. Oxidative stress is involved in central features of atherosclerosis. Platelet-derived microvesicles (PMVs) could be important mediators between oxidative stress and platelet activation. CD36 could be a receptor of PMVs, thus generating a PMV-CD36 complex. We aimed to investigate the detailed pathway by which oxidative damage contributes to platelet activation by the PMV-CD36 complex. We found that oxidized low-density lipoprotein stimulated the generation of PMVs. PMVs enhanced normal platelet activation, as assessed by the expression of integrin alpha(IIb)beta3, secretion of soluble P-selectin and platelet aggregation, but CD36-deficient platelets were not activated by PMVs. The function of the PMV-CD36 complex was mediated by the MKK4/JNK2 signaling axis. Meanwhile, PMVs increased the level of 8-iso-prostaglandin-F2alpha, a marker of oxidative stress, in a CD36- and phosphatidylserine-dependent manner. We concluded that PMVs are important mediators between oxidative stress and platelet activation. PMVs and CD36 may be effective targets for preventing platelet activation in cardiovascular diseases. PMID- 22064973 TI - N-[(E)-4-(Methyl-sulfon-yl)benzyl-idene]-3-nitro-aniline. AB - In the title compound, C(14)H(12)N(2)O(4)S, the dihedral angle between the two aromatic rings is 35.65 (12) degrees . The crystal packing is stabilized by weak C-H?O hydrogen bonds and aromatic pi-pi ring stacking inter-actions [minimum ring centroid separation = 3.697 (3) A]. PMID- 22064972 TI - The interaction of ApoA-I and ABCA1 triggers signal transduction pathways to mediate efflux of cellular lipids. AB - Reverse cholesterol transport (RCT) has been characterized as a crucial step for antiatherosclerosis, which is initiated by ATP-binding cassette A1 (ABCA1) to mediate the efflux of cellular phospholipids and cholesterol to lipid-free apolipoprotein A-I (apoA-I). However, the mechanisms underlying apoA-I/ABCA1 interaction to lead to the lipidation of apoA-I are poorly understood. There are several models proposed for the interaction of apoA-I with ABCA1 as well as the lipidation of apoA-I mediated by ABCA1. ApoA-I increases the levels of ABCA1 protein markedly. In turn, ABCA1 can stabilize apoA-I. The interaction of apoA-I with ABCA1 could activate signaling molecules that modulate posttranslational ABCA1 activity or lipid transport activity. The key signaling molecules in these processes include protein kinase A (PKA), protein kinase C (PKC), Janus kinase 2 (JAK2), Rho GTPases and Ca2+, and many factors also could influence the interaction of apoA-I with ABCA1. This review will summarize these mechanisms for the apoA-I interaction with ABCA1 as well as the signal transduction pathways involved in these processes. PMID- 22064974 TI - Concordance rates of Doppler ultrasound and CT angiography in the grading of carotid artery stenosis: a systematic literature review. AB - Physicians have been increasingly relying on noninvasive imaging methods to grade carotid stenosis. The accuracy of Doppler ultrasound (DUS) and CT angiography (CTA) versus intra-arterial angiography (IA) has been assessed in many studies and at least two meta-analyses. Here, we performed a systematic review of studies that compared DUS to CTA. In a PubMed review of the literature from 2000 to 2009, we found 12 studies that compared DUS and CTA-based grading of carotid stenosis. Only 4 of them included at least 20 patients and provided data to classify the diseased arteries into the following categories: mild, moderate or severe NASCET stenosis or occlusion. We extracted 431 arteries from 244 patients (range per study: 48-164). It was not possible to distinguish symptomatic from asymptomatic stenoses. Nearly half arteries had severe stenosis (46% based on DUS and 43% based on CTA). The weighted kappa was 0.85 (95% CI 0.76-0.94), and the accuracy was 0.78. When the arteries were classified into medical and potentially surgical groups, the kappa was 0.76 (95% CI 0.70-0.83), and the accuracy was 0.89. Overall, 17% of the stenoses classified as medical based on DUS were reclassified as surgical based on CTA and 14% of the stenoses classified as medical based on CTA were reclassified as surgical based on DUS. The sparse available data comparing DUS and CTA suggest that the grading of a carotid stenosis as medical or potentially surgical remains uncertain in a relatively high proportion of patients. PMID- 22064975 TI - Seroconversion of anti-aquaporin-4 antibody in NMO spectrum disorder: a case report. PMID- 22064976 TI - Investigation of autonomic function in idiopathic REM sleep behavior disorder. AB - Idiopathic REM sleep behavior disorder (iRBD) has been suggested as an early "pre motor" stage of Parkinson's disease (PD) in a significant proportion of cases. We investigated autonomic function in 15 consecutive iRBD patients and compared these findings to PD patients and healthy controls. All participants underwent cardiovascular autonomic function testing, and were rated on the COMPASS scale. Symptomatic orthostatic hypotension was present in two iRBD patients, two PD patients and none of the healthy controls. In the tilt table examination, blood pressure changes were similar between iRBD patients and healthy controls. In the PD group, blood pressure drops were more pronounced. In the orthostatic standing test, iRBD patients had higher blood pressure changes than healthy controls. Highest drops were found in PD. Valsalva ratio was lower in iRBD and PD compared to healthy controls. Total COMPASS score was higher in iRBD compared to healthy controls. Highest scores were found in PD. These results support the presence of autonomic dysfunction in iRBD. On several measures, dysfunction was intermediate between healthy controls and PD consistent with the concept that iRBD can be manifestation of synuclein-associated neurodegenerative disorders. Follow-up studies are needed to determine whether iRBD patients with dysfunction on several autonomic domains are at particular risk for developing one of these diseases. PMID- 22064977 TI - Vivid visual mental imagery in the absence of the primary visual cortex. AB - The role of the primary visual cortex in visual mental imagery has provided significant debate in the imagery literature. Functional neuroimaging studies show considerable variation depending on task and technique. Patient studies can be difficult to interpret due to the diverse nature of cortical damage. The type of cortical damage in patient SBR is exceedingly rare as it is restricted to the gray matter of the calcarine sulcus. In this study, we show that in spite of his near-complete cortical blindness, SBR exhibits vivid visual mental imagery both behaviorally and when measured with functional magnetic resonance imaging. The pattern of cortical activation to visual mental imagery in SBR is indistinguishable from individual sighted subjects, in contrast to the visual perceptual responses, which are greatly attenuated. PMID- 22064978 TI - 2-(5-{6-[5-(Pyrazin-2-yl)-1H-1,2,4-triazol-3-yl]pyridin-2-yl}-1H-1,2,4-triazol-3 yl)pyrazine. AB - In the title mol-ecule, C(17)H(11)N(11), the five rings are almost coplanar [maxium deviation 0.1949 (1) A]. The dihedral angles between the two pyrazine rings and the two triazole rings are 1.52 (4) and 2.51 (5) degrees , respectively. The central pyridine ring forms dihedral angles of 5.57 (1) and 1.71 (1) degrees with the two triazole rings. The crystal packing consists of a three-dimensional network structure generated by inter-molecular N-H?N hydrogen bonds. The crystal structure is further consolidated by pi-pi stacking [centroid to-centroid distances 3.599 (10) and 4.769 (13) A]. PMID- 22064981 TI - Subpubic cyst. Subpubic degenerative cyst arising from the fibrocartilage of the pubic symphysis. PMID- 22064982 TI - Reliability of radiographic parameters in adults with hip dysplasia. AB - OBJECTIVE: To assess the reliability of radiographic measurements in adults previously treated for developmental dysplasia of the hip (DDH) and to clarify whether these parameters differ according to position of the patient (supine versus standing). MATERIALS AND METHODS: Fifty-one patients (41 females and 10 males) with 63 affected hips were included in the study. The mean follow-up period was 45 (44-49) years in the patients who had not undergone total hip replacement (THR). Anteroposterior radiographs of the pelvis were taken with the patient in the supine and in the standing position. Measurements used for residual hip dysplasia were center-edge (CE) angle and migration percentage (MP). The joint space width (JSW) was measured at three or four locations of the upper, weight-bearing part of the joint, and the shortest distance was termed the minimum joint space width (minJSW). One radiologist and one orthopaedic surgeon, each with more than 30 years of experience, independently measured the radiographic parameters. RESULTS: The limits of agreement (LOA) of the CE angle (mean interobserver difference +/- 2SD) were within the range -8 to 7 degrees . The LOA of the MP were in the range -8 to 8% and of the minJSW -0.6 to 1.1 mm. The mean differences in CE angle between supine and standing radiographs (supine standing) ranged from -1.1 to 0.0 degrees and the mean differences in MP between supine and standing positions were below 1%. The mean positional differences in minJSW were below 0.1 mm and were not statistically significant. CONCLUSION: The interobserver variations with regard to CE angle, MP, and minJSW were moderate, indicating that these are reliable measurements in clinical practice. Femoral head coverage and JSW did not significantly differ between supine and weight-bearing positions. PMID- 22064983 TI - Cone-beam computed tomography arthrography: an innovative modality for the evaluation of wrist ligament and cartilage injuries. AB - PURPOSE: Cone-beam computed tomography (CBCT) has become an important modality in dento-facial imaging but remains poorly used in the exploration of the musculoskeletal system. The purpose of this study was to prospectively evaluate the performance and radiation exposure of CBCT arthrography in the evaluation of ligament and cartilage injuries in cadaveric wrists, with gross pathology findings as the standard of reference. MATERIALS AND METHODS: Conventional arthrography was performed under fluoroscopic guidance on 10 cadaveric wrists, followed by MDCT acquisition and CBCT acquisition. CBCT arthrography and MDCT arthrography images were independently analyzed by two musculoskeletal radiologists working independently and then in consensus. The following items were observed: scapholunate and lunotriquetral ligaments, triangular fibrocartilage complex (TFCC) (tear, integrity), and proximal carpal row cartilage (chondral tears). Wrists were dissected and served as the standard of reference for comparisons. Interobserver agreement, sensitivity, specificity, and accuracy were determined. Radiation dose (CTDI) of both modalities was recorded. RESULTS: CBCT arthrography provides equivalent results to MDCT arthrography in the evaluation of ligaments and cartilage with sensitivity and specificity between 82 and 100%, and interobserver agreement between 0.83 and 0.97. However, radiation dose was significantly lower (p < 0.05) for CBCT arthrography than for MDCT arthrography with a mean CTDI of 2.1 mGy (range 1.7-2.2) versus a mean of 15.1 mGy (range 14.7-16.1). CONCLUSION: CBCT arthrography appears to be an innovative alternative to MDCT arthrography of the wrist as it allows an accurate and low radiation dose evaluation of ligaments and cartilage. PMID- 22064984 TI - Society of Skeletal Radiology 2011 Annual Meeting. AB - Peer-reviewed abstracts presented at the 2011 Society of Skeletal Radiology (SSR) Annual Meeting were reviewed again following oral presentation. Topics representing new concepts, new or novel imaging techniques, and instructive case series involving the musculoskeletal system, felt to be of potential interest to investigators and practicing clinicians, have been highlighted in this compilation and analysis. ePoster highlights have also been submitted. PMID- 22064985 TI - Ultrasonographic analysis of subcutaneous angiolipoma. AB - OBJECTIVE: To describe and analyze the ultrasonographic appearance of subcutaneous angiolipoma in pathology-proven cases. MATERIALS AND METHODS: We retrospectively searched the January 2004 to May 2011 surgical pathology database for cases of pathology-proven angiolipoma. The ultrasonographic findings were analyzed for angiolipoma size, shape, margin, echo texture, echogenicity, acoustic enhancement, calcifications, and color Doppler flow. RESULTS: Of 31 angiolipomas, 19 lesions occurred in an upper extremity, one in a lower extremity, nine in the chest and abdominal wall, and two in the back. The mean tumor size was 17.7 mm. Twenty-five cases (80%) appeared as oval mass and all tumors had well-defined margins. All cases showed hyperechoic; 14 (45%), homogeneous; 17 (55%), heterogeneous. Seven cases (23%) showed blood flow in the mass. Acoustic enhancement and calcification was not shown in any cases. A correct preoperative diagnosis was made in three cases (10%) by ultrasonography. CONCLUSIONS: Most subcutaneous angiolipomas are oval-shaped, have well-defined margins, and hyperechoic appearance on ultrasonography. Although color Doppler flow of subcutaneous angiolipoma is not seen in many cases, it may helpful in differentiating angiolipoma from ordinary subcutaneous lipoma. PMID- 22064986 TI - Comparison of autophotomontage software programs in eyes with CMV retinitis. AB - PURPOSE: Automated mosaic software programs are used to stitch together overlapping retinal fundus photographs. The performance of these programs in eyes with retinal diseases has not been independently evaluated. This study compares the quality of the mosaic products of three autophotomontage software programs, using digital fundus photographs of eyes with cytomegalovirus (CMV) retinitis. METHODS: Photographs of 99 eyes with CMV retinitis of 94 patients with HIV were taken at Maharaj Nakorn Chiang Mai Hospital in Chiang Mai, Thailand. Automated mosaic images were created for each of the 99 eyes by three different commercially available programs: IMAGEnet (Topcon, Oakland, NJ), i2k Retina (DualAlign LLC, Clifton Park, NY), and AutoMontage (OIS, Sacramento, CA). Three masked graders ranked each set of mosaics for each eye. The graders also assessed the overall image quality and documented mosaic artifacts in each image. RESULTS: i2k Retina was ranked as the best program (70%-88%) more often than AutoMontage (10%-33%, P < 0.001) or IMAGEnet (0%-4%, P < 0.001) for creating automontages from digital fundus photographs of eyes with CMV retinitis. Acceptable quality mosaic images were reported most commonly for i2k Retina (93%-94%) and AutoMontage (91%-95%), followed by IMAGEnet (27%-56%, P < 0.001). IMAGEnet had a significantly higher percentage of mosaic errors than did either i2k Retina or AutoMontage (P < 0.001). CONCLUSIONS: In eyes with CMV retinitis, both the i2k Retina and AutoMontage software packages appear to create higher quality mosaics than does IMAGEnet. Automated retinal mosaic imaging may be valuable in diagnosing CMV retinitis and observing disease progression. PMID- 22064987 TI - Cultured autologous oral mucosal epithelial cell sheet (CAOMECS) transplantation for the treatment of corneal limbal epithelial stem cell deficiency. AB - PURPOSE: Total bilateral corneal limbal epithelial stem cell deficiency (LSCD) cannot be treated with the surgical transplantation of autologous limbus or cultured autologous limbal epithelium. Transplantation of allogenic limbal epithelium is possible but requires immunosuppressive treatments. Cultured autologous oral mucosal epithelial cell sheet (CAOMECS) is a transparent, resistant, viable, and rapidly bioadhesive cell sheet, cultured with the UpCell Insert technology (CellSeed, Inc., Tokyo, Japan), which allows for grafting onto the patient's corneal stroma without suturing. It has therefore been proposed as an alternative treatment for LSCD. METHODS: The objectives were to assess the safety and efficacy of CAOMECS, using a prospective Gehan's design. Safety was measured in terms of ocular adverse events during the study period, and efficacy was measured using a composite criterion based on epithelial defect, punctate epithelial keratopathy, conjunctival epithelium on the cornea, number of vascular pediculi, and vessel activity. RESULTS: CAOMECS was found to be safe and effective. In total, 26 eyes of 25 patients received a graft. Two patients experienced serious adverse events classified as not product related. Twenty-five patients were included in the efficacy analysis, as one patient was lost to follow-up. The treatment was found to be effective in 16 of 25 patients at 360 days after grafting. Of the 23 patients who completed follow-up at 360 days, 22 had no ulcers, and 19 showed a decrease in the severity of the punctate epithelial keratopathy. CONCLUSIONS: CAOMECS is a well-tolerated and safe tissue engineered product. These results suggest its efficacy for reconstructing the ocular surface in patients with total bilateral corneal LSCD. PMID- 22064988 TI - Molecular characterization of explant cultured human oral mucosal epithelial cells. AB - PURPOSE: To culture and characterize oral mucosal epithelial cells (OMEC) grown on de-epithelialized human amniotic membrane (HAM) to explore their suitability as autografts in patients with bilateral ocular surface disease (OSD) and limbal stem cell deficiency. METHODS: Oral biopsy samples were obtained from 20 patients undergoing oral reconstructive surgery, with informed consent and Institutional Ethics Committee approval. Morphologic studies, transmission electron microscopy (TEM), reverse transcriptase (RT) PCR and immunocytochemistry were used to characterize the OMEC. RESULTS: Morphologic studies and TEM revealed a confluent sheet of proliferating, stratified oral epithelial cells connected to each other by desmosomes, containing intracellular cytokeratins and abundant mucin granules. These characteristics were further corroborated and elucidated by RT-PCR and immunocytochemistry. The presence of markers of differentiated, stratified epithelial cells (cytokeratin K3, K4, K13, and connexin 43), progenitor stem cell cell markers (p63, p75, beta1-integrin/CD29, and ABCG2), and a variety of predominantly membrane-bound and a few gel-forming mucins (MUC 1, 5B, 6, 13, 15, and 16) was established. CONCLUSIONS: Cultured OMEC have the potential to act as autografts for ocular surface reconstruction in patients with bilateral ocular surface disease and can prove to be particularly beneficial to ameliorate the mucin deficiency state in dry eye associated with OSD. PMID- 22064989 TI - Cross-linking with ultraviolet-a and riboflavin reduces corneal permeability. AB - PURPOSE: To investigate the effect of cross-linking treatment on corneal permeability in a live animal model. METHODS: Rabbit eyes were selected at random to be left unoperated or to undergo epithelial debridement with or without treatment consisting of cross-linking (CXL) with riboflavin and ultraviolet-A. Nine eyes received a total dose of 3.6 J/cm2 and after epithelial healing the corneas were placed in a two-chamber system for quantification of the diffusion of fluorescein compared with controls. Thirty eyes received a total dose of 5.4 J/cm2 and, after epithelial healing, in vivo corneal permeability was quantified as the pupillary response over a 30-minute period to a dose of topical pilocarpine compared with controls. RESULTS: In the ex vivo assay, the mean permeability coefficient in the CXL group (2.42 * 10-7) was reduced when compared with the unoperated controls (3.73 * 10-7; P = 0.007) and to the eyes that received epithelial debridement alone (3.74 * 10-7; P = 0.01). In the in vivo permeability assay, the change in pupillary diameter at 30 minutes after pilocarpine administration was smaller in the CXL group (-1.9 mm), compared with the epithelial debridement group (-2.6 mm; P < 0.001) and with the unoperated controls (-2.7 mm; P = 0.003). CONCLUSIONS: Corneal cross-linking with ultraviolet-A and riboflavin results in a statistically significant reduction in corneal permeability. These findings suggest that dosing of topical medications may need to be increased in eyes with a history of CXL to achieve expected therapeutic effects, and they may have implications for the long-term health of the cornea. PMID- 22064990 TI - Substratum compliance regulates human trabecular meshwork cell behaviors and response to latrunculin B. AB - PURPOSE: To determine the impact of substratum compliance and latrunculin-B (Lat B), both alone and together, on fundamental human trabecular meshwork (HTM) cell behavior. Lat-B is a reversible actin cytoskeleton disruptor that decreases resistance to aqueous humor outflow and decreases intraocular pressure. METHODS: HTM cells were cultured on polyacrylamide hydrogels possessing values for compliance that mimic those reported for normal and glaucomatous HTM, or tissue culture plastic (TCP). Cells were treated with 0.2 MUM or 2.0 MUM Lat-B in dimethyl sulfoxide (DMSO) or DMSO alone. The impact of substratum compliance and/or Lat-B treatment on cell attachment, proliferation, surface area, aspect ratio, and migration were investigated. RESULTS: HTM cells had profoundly decreased attachment and proliferation rates when cultured on hydrogels possessing compliance values that mimic those found for healthy HTM. The effect of Lat-B treatment on HTM cell surface area was less for cells cultured on more compliant hydrogels compared with TCP. HTM cell migration was increased on stiffer hydrogels that mimic the compliance of glaucomatous HTM and on TCP in comparison with more compliant hydrogels. Lat-B treatment decreased cellular migration on all surfaces for at least 7 hours after treatment. CONCLUSIONS: Substratum compliance profoundly influenced HTM cell behaviors and modulated the response of HTM cells to Lat-B. The inclusion of substratum compliance that reflects healthy or glaucomatous HTM results in cell behaviors and responses to therapeutic agents in vitro that may more accurately reflect in vivo conditions. PMID- 22064991 TI - The effects of nicotine on the human electroretinogram. AB - PURPOSE: To examine the effects of nicotine on responses from the human retina measured electrophysiologically. METHODS: Electroretinogram (ERG) responses were obtained from ten healthy, visually normal adults who were nonsmokers. Nicotine (2 and 4 mg) and a placebo were administered in the form of gum 30 minutes before testing in two separate experiments. ERG responses were collected and analyzed using a full-field ERG system. Responses were recorded from one eye of each subject using a bipolar contact-lens electrode. Intensity-response curves were obtained under both dark- and light-adapted conditions. In experiment 1, both dark- and light-adapted tests were completed sequentially. In experiment 2, only light-adapted testing was performed. Intensity-response functions were analyzed using the Naka-Rushton equation. RESULTS: In experiment 1, compared with placebo, dark-adapted b-wave amplitude responses decreased significantly after chewing gum containing both 2 and 4 mg of nicotine. Under light-adapted conditions, the peak b-wave amplitude was significantly decreased after chewing gum containing 4 mg of nicotine. In experiment 2, light-adapted b-wave amplitudes were increased after 4 mg nicotine. Oscillatory potentials were measured but no significant effects under nicotine were observed. CONCLUSIONS: To the knowledge of the authors, this is the first demonstration that nicotine by itself affects responses in the human retina. These data support reports of the expression of nicotinic acetylcholine receptors in rabbit and nonhuman primate retina. PMID- 22064992 TI - Keratin 13 immunostaining in corneal impression cytology for the diagnosis of limbal stem cell deficiency. AB - PURPOSE: The aim of this study was to develop a validated, reliable, and minimally invasive technique for diagnosing limbal stem cell deficiency (LSCD) by immunocytochemical detection of conjunctival and corneal keratins on epithelial cells collected by impression cytology (IC). METHODS: After validation of labeling techniques on a cohort of 10 healthy control patients, keratins K12, K13, and K19 were labeled on corneal IC of 10 eyes suspected of LSCD. Positive scores for the conjunctival markers K13/K19, coupled with the rarity of the corneal marker K12, were diagnostic proof of LSCD. RESULTS: IC is a reliable and noninvasive technique for collecting epithelial cells. The labeling validation phase has permitted K3 labeling to be eliminated due to lack of corneal specificity. Among patients with LSCD, nine samples were diagnosed with LSCD (K13+/K19+), which was severe (K12-) in eight cases and mild (K12+) in one case. One sample could not be analyzed due to lack of cells. CONCLUSIONS: K13 has shown to be a new marker of conjunctival differentiation. The immunocytochemical search for the K13/K19 couple by corneal IC provides a simple and reliable method for diagnosing LSCD, whereas the level of K12 could provide a score of disease severity. On the other hand, the authors question the corneal specificity of K3 as conventionally established. PMID- 22064993 TI - Involvement of EphB/Ephrin-B signaling in axonal survival in mouse experimental glaucoma. AB - PURPOSE: To examine the functional significance of EphB/ephrin-B upregulation in mouse experimental glaucoma. METHODS: In a loss-of-function approach, mouse mutants lacking EphB2 (EphB2(-/-)) or EphB3 (EphB3(-/-)) protein, and mutants expressing EphB2 truncated in the C-terminus (EphB2(lacZ/lacZ)) were subjected to laser-induced ocular hypertension (LIOH), an experimental mouse model of glaucoma. The number of optic nerve axons was counted in paraphenylenediamine (PPD)-stained sections and compared between EphB mutants and wild type littermates. In a gain-of-function approach, retina/optic nerve explants obtained from LIOH-treated animals were exposed to EphB2-Fc recombinant proteins or Fc control proteins. Tissue sections through the optic nerve head (ONH) were labeled with neuron-specific anti-tubulin beta-III antibody to determine axonal integrity. RESULTS: Both EphB2 and EphB3 null mutant mice exhibited more severe axonal degeneration than wild type littermates after treatment with LIOH. Mutant mice in which the C-terminal portion of EphB2 is truncated had an intermediate phenotype. Application of EphB2-Fc recombinant protein to LIOH-treated optic nerve explants resulted in greater sparing of tubulin beta-III-containing retinal ganglion cell (RGC) axons. CONCLUSIONS: These results provide genetic evidence in mice that both EphB/ephrin-B forward and reverse signaling feed into an endogenous pathway to moderate the effects of glaucomatous insult on RGC axons. LIOH-induced axon loss is maintained in retina/optic nerve explants after removal from an ocular hypertensive environment. Exogenous application of EphB2 protein enhances RGC axon survival in explants, suggesting that modulation of Eph/ephrin signaling may be of therapeutic interest. PMID- 22064994 TI - p53-regulated increase in oxidative-stress--induced apoptosis in Fuchs endothelial corneal dystrophy: a native tissue model. AB - PURPOSE: This study compared susceptibility of Fuchs endothelial corneal dystrophy (FECD) and normal corneal endothelial cells (CECs) to oxidative stress, and studied the mechanism of oxidative-stress-induced apoptosis in FECD-affected endothelium. METHODS: For in vitro studies, immortalized normal and FECD human corneal endothelial cell lines (HCECi and FECDi, respectively) were exposed to tert-butyl hydroperoxide (tBHP). Apoptotic cell populations were distinguished using flow cytometry. Reactive oxygen species production was measured by a horseradish peroxidase assay. For ex vivo studies, CECs were exposed to tBHP. Oxidative DNA damage and apoptosis were assessed by anti-8-hydroxydeoxyguanosine antibody and TUNEL assay, respectively. p53 and phospho-p53 levels were assessed by Western blot and immunohistochemistry. RESULTS: Flow cytometry revealed a higher rate of apoptosis in FECDi than that in HCECi after exposure to 0.5 mM (P=0.010) and 1.0 mM tBHP (P=0.041). Further analysis showed increased production of H2O2 by FECDi than that by HCECi. Oxidative DNA damage increased in both normal and FECD CECs after exposure to 0.5 mM tBHP (P=0.031 and 0.022, respectively), leading to a 21% increase in TUNEL-positive CECs in FECD (P=0.015) but no change in normal. Baseline p53 expression was twofold higher in FECD than that in normal endothelium (P=0.002). Immunofluorescence revealed an increase in p53 and phospho-p53 levels in FECD compared with that in normal endothelium. CONCLUSIONS: FECD CECs are more susceptible to oxidative DNA damage and oxidative stress-induced apoptosis than normal. Increased activation of p53 in FECD suggests that it mediates cell death in susceptible CECs. The authors conclude that p53 plays a critical role in complex mechanisms regulating oxidative-stress induced apoptosis in FECD. PMID- 22064995 TI - Ocular biocompatibility of nitinol intraocular clips. AB - PURPOSE: To evaluate the tolerance and biocompatibility of a preformed nitinol intraocular clip in an animal model after anterior segment surgery. METHODS: Yucatan mini-pigs were used. A 30-gauge prototype injector was used to attach a shape memory nitinol clip to the iris of five pigs. Another five eyes received conventional polypropylene suture with a modified Seipser slip knot. The authors compared the surgical time of each technique. All eyes underwent standard full field electroretinogram at baseline and 8 weeks after surgery. The animals were euthanized and eyes collected for histologic analysis after 70 days (10 weeks) postsurgery. The corneal thickness, corneal endothelial cell counts, specular microscopy parameters, retina cell counts, and electroretinogram parameters were compared between the groups. A two sample t-test for means and a P value of 0.05 were use for assessing statistical differences between measurements. RESULTS: The injection of the nitinol clip was 15 times faster than conventional suturing. There were no statistical differences between the groups for corneal thickness, endothelial cell counts, specular microscopy parameters, retina cell counts, and electroretinogram measurements. CONCLUSIONS: The nitinol clip prototype is well tolerated and showed no evidence of toxicity in the short-term. The injectable delivery system was faster and technically less challenging than conventional suture techniques. PMID- 22064996 TI - Relationship of ocular biometry and retinal vascular caliber in preschoolers. AB - PURPOSE: To systematically examine the association between ocular biometry and retinal vascular caliber in Singapore Chinese preschoolers aged 48 to 72 months. METHODS: A total of 469 Singapore Chinese children aged 48 to 72 months were recruited through the Strabismus, Amblyopia and Refractive Error Study in Singaporean Chinese Preschoolers (STARS) from 2006 to 2008. According to standardized protocols, cycloplegic autorefraction, ocular biometry measurements, and retinal photography were performed. Retinal vascular caliber was measured quantitatively and was summarized as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively. Ocular magnification was corrected by using the Bengtsson formula. RESULTS: The mean retinal arteriolar and venular calibers were 156.08 MUm and 219.55 MUm in boys, and 161.96 MUm and 224.25 MUm in girls, respectively. In multiple linear regression adjusted for age, sex, father's education, parental myopia history, mean arterial blood pressure, body mass index, and spherical equivalent, each 1.0 mm increase in axial length was associated with a 3.52 MUm decrease in retinal arteriolar caliber (P = 0.023) and a 5.55 MUm decrease in retinal venular caliber (P = 0.008). Each 1.00 mm increase in corneal curvature was associated with a 13.79 MUm decrease (P = 0.004) in retinal venular caliber. CONCLUSIONS: In very young children aged 48 to 72 months, narrower retinal arteriolar and venular caliber was associated with elongated axial length. Narrower retinal venular caliber was associated with larger corneal curvature. This suggests that the major structural correlate of myopia might have an effect on retinal microvasculature from early childhood. PMID- 22064997 TI - 5,13-Disulfamoyl-1,9-diazatetracyclo[7.7.1.0.0]heptadeca-2(7),3,5,10,12,14-hexaen 1-ium chloride. AB - In the title salt, C(15)H(17)N(4)O(4)S(2) (+).Cl(-), the chloride anion is disordered over two positions with occupancies of 0.776 (6) and 0.224 (6). The cation adopts an L shape and the dihedral angle between the benzene rings is 82.5 (3) degrees . In the crystal, inversion dimers of cations linked by pairs of N H?N hydrogen bonds occur, with the bond arising from the protonated N atom. The cationic dimers are linked into chains via the disordered chloride ions by way of N-H?Cl hydrogen bonds and N-H?O, C-H?O and C-H?Cl inter-actions also occur, which help to consolidate the three-dimensional network. PMID- 22064998 TI - 4-(4-Chloro-phen-yl)-8-methyl-2-oxo-1,2,5,6,7,8-hexa-hydro-quinoline-3 carbonitrile. AB - The six-membered N-heterocyclic ring of the title compound, C(17)H(15)ClN(2)O, is fused with a methyl-substituted cyclo-hexene ring. The approximately planar nitro gen-bearing ring (r.m.s. deviation 0.019 A) is aromatic, and the N atom shows a trigonal-planar coordination; its benzene substituent is aligned at 77.1 (1) degrees . The cyclo-hexene ring adopts a half-chair conformation. In the crystal, inversion-related mol-ecules are linked by pairs of N-H?O hydrogen bonds, generating dimers. PMID- 22064999 TI - Pharmacogenetics for oncology practice. PMID- 22065000 TI - Germline genetic testing to predict drug response and toxicity in oncology- reality or fiction? AB - In addition to 6-mercaptopurine, 5-fluorouracil and irinotecan, the United States Food and Drug Administration (US FDA) has recently recommended label change for tamoxifen, to include pharmacogenetic information on treatment outcome. With the increasing availability of pharmacogenetic testing, on germline as well as somatic mutations, oncologists are now able to identify individuals at risk of severe treatment toxicity or poor treatment response. However, there are still knowledge gaps to fill before rationalised therapy based on pharmacogenetics can be fully integrated into clinical practice. This review provides an overview on the application of pharmacogenetic testing for germ line mutations in oncology to predict response and toxicity. PMID- 22065001 TI - Inter-ethnic differences--how important is it in cancer treatment? AB - It is now well recognised that there are inter-ethnic differences accounting for variations in both pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, resulting in differences in drug responses. Treating physicians should be aware of pharmacogenetic differences that may exist between the races while extrapolating data generated from other populations to their own patients in order to ensure optimal treatment response and minimise toxicity. This is especially crucial in the practice of oncology where many anti-cancer drugs have narrow therapeutic indices. This paper discusses some commonly used drugs in cancer treatment where inter-ethnic differences in drug safety and efficacy are known to exist that are relevant to the Asian physician. PMID- 22065002 TI - Tumour genetics and genomics to personalise cancer treatment. AB - Personalising cancer treatment to optimise therapeutic efficacy while minimising exposure to the toxicities of ineffective drugs is the holy grail of medical oncology. Clinical parameters and conventional histopathological characterisations of cancers are no longer adequate to guide the practising oncologists in treatment planning. The explosion of knowledge in cancer molecular biology has led to the availability of tumour-specific molecules that serve as predictive and prognostic markers. In breast cancer, HER-2 positivity is a good predictor for success of anti-HER-2 trastuzumab monoclonal antibody therapy. K ras mutational status predicts the likelihood of response to anti-EGFR monoclonal antibodies in advanced colorectal cancers. Similarly, EGFR mutational status in pulmonary adenocarcinoma is highly predictive for responses or otherwise to tyrosine kinase inhibitors. Notwithstanding our deeper understanding of tumour biology and the availability of predictive and prognostic laboratory tools, we are still far from achieving our dream of the perfect personalised cancer treatment, as each tumour in a particular patient is unique to itself. A much coveted, real-time, anti-tumour drug sensitivity testing in the future may one day pave the way for truly treating the right tumour with the right drug in the right patient. PMID- 22065003 TI - Challenges and pitfalls in the introduction of pharmacogenetics for cancer. AB - There have been several success stories in the field of pharmacogenetics in recent years, including the analysis of HER2 amplification for trastuzumab selection in breast cancer and VKORC1 genotyping for warfarin dosing in thrombosis. Encouraging results from these studies suggest that genetic factors may indeed be important determinants of drug response and toxicity for at least some drugs. However, to apply pharmacogenetics appropriately, a thorough understanding of the scope and limitations of this field is required. The challenges include an appreciation of biological variability, logistical issues pertaining to the proper management of information, the need for robust methods and adequate sample quality with well-designed workflows. At the same time, the economics of pharmacogenetic testing from the perspective of clinicians, patients, governments, insurance companies and pharmaceutical companies will play an important role in determining its future use. Ethical considerations such as informed consent and patient privacy, as well as the role of regulatory bodies in addressing these issues, must be fully understood. Only once these issues are properly dealt with can the full benefits of pharmacogenetics begin to be realised. PMID- 22065004 TI - Perforated colorectal cancer: an important differential diagnosis in all presumed diverticular abscesses. PMID- 22065005 TI - Eosinophilic gastroenteritis presenting with duodenal obstruction and ascites. PMID- 22065006 TI - No coma, but expressive dysphasia with cerebellar signs: an unique presentation of cerebral malaria. PMID- 22065007 TI - A good prognosis of central pontine myelinolysis in a type II diabetic patient. PMID- 22065008 TI - Two cases of glossopharyngeal neuralgia successfully treated with pulsed radiofrequency treatment. PMID- 22065009 TI - A verrucous 'tumour' on the scalp. PMID- 22065010 TI - 9-Hy-droxy-4,8-dimethyl-12-(pyrrolidin-1-ylmeth-yl)-3,14-dioxatricyclo [9.3.0.0]tetra-dec-7-en-13-one. AB - The title compound, C(19)H(29)O(4), was synthesized from 9alpha-hy-droxy parthenolide (9alpha-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxatricyclo [9.3.0.0(2,4)]tetra-dec-7-en-13-one), which was isolated from the chloro-form extract of the aerial parts of Anvillea radiata. The mol-ecule is built up from two fused five- and ten-membered rings with the pyrrolidin-1-ylmethyl group as a substituent. The five-membered lactone ring has an envelope conformation, whereas the ten-membered and pyrrolidine rings display approximate chair-chair and twisted conformations, respectively. The dihedral angle between the ten-membered ring and the lactone ring is 18.01 (19) degrees . An intra-molecular O-H?N hydrogen bond occurs. The crystal structure is stabilized by weak inter-molecular C-H?O hydrogen-bonding inter-actions. PMID- 22065011 TI - P2Y purinoceptors induce changes in intracellular calcium in acinar cells of rat lacrimal glands. AB - Adenosine 5'-triphosphate (ATP) is an extracellular signal that regulates various cellular functions. Cellular secretory activities are enhanced by ATP as well as by cholinergic and adrenergic stimuli. The present study aimed to determine which purinoceptors play a role in ATP-induced changes in the intracellular concentration of calcium ions ([Ca2+](i)) and in the fine structure of acinar cells of rat lacrimal glands. ATP induced exocytotic structures, vacuolation and an increase in [Ca2+](i) in acinar cells. The removal of extracellular Ca2+ or the use of Ca2+ channel blockers partially inhibited the ATP-induced [Ca2+](i) increase. U73122 (an antagonist of PLC) and heparin (an antagonist of IP3 receptors) did not completely inhibit the ATP-induced [Ca2+](i) increase. P1 purinoceptor agonists did not induce any changes in [Ca2+](i), whereas suramin (an antagonist of P2 receptors) completely inhibited ATP-induced changes in [Ca2+](i). A P2Y receptor agonist, 2-MeSATP, induced a strong increase in [Ca2+](i), although UTP (a P2Y2,4,6 receptor agonist) had no effect, and reactive blue 2 (a P2Y receptor antagonist) resulted in partial inhibition. The potency order of ATP analogs (2-MeSATP > ATP >>> UTP) suggested that P2Y1 played a significant role in the cellular response to ATP. BzATP (a P2X7 receptor agonist) induced a small increase in [Ca2+](i), but alpha,beta-meATP (a P2X1,3 receptor agonist) had no effect. RT-PCR indicated that P2X2,3,4,5,6,7 and P2Y1,2,4,12,14 are expressed in acinar cells. In conclusion, the response of acinar cells to ATP is mediated by P2Y (especially P2Y1) as well as by P2X purinoceptors. PMID- 22065012 TI - Estimation of regional bone metabolism from whole-body 18F-fluoride PET static images. AB - PURPOSE: We evaluate a new quantitative method of acquiring and analysing (18)F positron emission tomography (PET) studies that enables regional bone plasma clearance (K ( i )) to be estimated from static scans acquired at multiple sites in the skeleton following a single injection of tracer. METHODS: Dynamic lumbar spine (18)F PET data from two clinical trials were used to simulate a series of static scans acquired 30-60 min after injection. Venous blood samples were taken at 30, 40, 50 and 60 min and K ( i ) evaluated by Patlak analysis and the static scan method. The data were used to evaluate the precision errors of the Patlak and static scan methods expressed as the percentage coefficient of variation (%CV) and compare their response to 6 months of treatment with the bone anabolic agent teriparatide. RESULTS: Static scan K ( i ) measurements 30-60 min after injection were highly correlated with the Patlak results (r > 0.99). The %CV for the static scan method was 17.5% 30 min after injection, decreasing to 14.5% at 60 min, compared with 13.0% for Patlak analysis. Response to teriparatide treatment was +25.2% for the static scan method compared with +24.3% for Patlak analysis. The mean ratio (SD) of the static scan and Patlak K ( i ) results was 1.006 (0.015) at 30 min after injection decreasing to 0.965 (0.015) at 60 min. CONCLUSION: (18)F-Fluoride bone plasma clearance can be estimated from a static scan and venous blood samples acquired 30-60 min after injection. The method enables K ( i ) to be estimated at multiple skeletal sites with a single injection of tracer. PMID- 22065013 TI - Prospective comparison of combined 18F-FDG and 18F-NaF PET/CT vs. 18F-FDG PET/CT imaging for detection of malignancy. AB - PURPOSE: Typically, (18)F-FDG PET/CT and (18)F-NaF PET/CT scans are done as two separate studies on different days to allow sufficient time for the radiopharmaceutical from the first study to decay. This is inconvenient for the patients and exposes them to two doses of radiation from the CT component of the examinations. In the current study, we compared the clinical usefulness of a combined (18)F-FDG/(18)F-NaF PET/CT scan with that of a separate (18)F-FDG-only PET/CT scan. METHODS: There were 62 patients enrolled in this prospective trial. All had both an (18)F-FDG-alone PET/CT scan and a combined (18)F-FDG/(18)F-NaF PET/CT scan. Of the 62 patients, 53 (85%) received simultaneous tracer injections, while 9 (15%) received (18)F-NaF subsequent to the initial (18)F-FDG dose (average delay 2.2 h). Images were independently reviewed for PET findings by two Board-Certified nuclear medicine physicians, with discrepancies resolved by a third reader. Interpreters were instructed to only report findings that were concerning for malignancy. Reading the (18)F-FDG-only scan first for half of the patients controlled for order bias. RESULTS: In 15 of the 62 patients (24%) neither the (18)F-FDG-only PET/CT scan nor the combined (18)F-FDG/(18)F-NaF PET/CT scan identified malignancy. In the remaining 47 patients who had PET findings of malignancy, a greater number of lesions were detected in 16 of 47 patients (34%) using the combined (18)F-FDG/(18)F-NaF PET/CT scan compared to the (18)F-FDG-only PET/CT scan. In 2 of these 47 patients (4%), the (18)F-FDG-only scan demonstrated soft tissue lesions that were not prospectively identified on the combined study. In 29 of these 47 patients (62%), the combined scan detected an equal number of lesions compared to the (18)F-FDG-only scan. Overall, 60 of all the 62 patients (97%) showed an equal or greater number of lesions on the combined scan than on the (18)F-FDG-only scan. CONCLUSION: The current study demonstrated that (18)F-FDG and (18)F-NaF can be combined in a single PET/CT scan by administering the two radiopharmaceuticals simultaneously or in sequence on the same day. In addition to patient convenience and reduced radiation exposure from the CT component, the combined (18)F-FDG/(18)F-NaF PET/CT scan appeared to increase the sensitivity for detection of osseous lesions compared to the (18)F FDG-only PET/CT scan in the studied population. PMID- 22065014 TI - C3 and C4 complement system components as biomarkers in the intermittent atopic asthma diagnosis. AB - OBJECTIVE: To analyze serum C3 and C4 complement system components with a view to their possible utility as biomarkers of intermittent atopic asthma. METHODS: Serum levels of the C3 and C4 complement components were assayed in 70 children aged from 3 to 14 years and with a history of "wheezy chest." After 2 years' outpatients follow-up and after application of inclusion and exclusion criteria, the children were divided into two groups: 40 children with intermittent atopic asthma and 30 children without asthma. None of the children in either group were treated with inhaled or systemic corticosteroids or long-acting bronchodilators. The two groups had similar ages according to Student's t test. The C3 and C4 component test results followed a normal distribution and were therefore compared using Student's t test with significance set at p < 0.05. RESULTS: The results for the group with intermittent atopic asthma were significantly elevated for C3 in 85.0% of the children, for C4 in 87.5% of the children, for both C3 and C4 in 72.5% of the children, and for either C3 or C4 in 97.5% of the children, when compared with the results for the children without asthma from the same age group. CONCLUSIONS: We observed an increase in the serum levels of the C3 and/or C4 components of the complement system in the majority of the patients with intermittent atopic asthma studied here, when compared with the results for children in the same age group without asthma. We conclude that the presence of elevated C3 and/or C4 complement components could represent a biomarker for diagnosis of intermittent atopic asthma. PMID- 22065015 TI - Management of priority mental disorders in the community. AB - As a part of designing a suitable model for mental health care delivery in rural India, a study of detection and management of priority mental disorders was carried out in 120 villages around rural mental health centre, Sakalwara in Bangalore District. During three and a half year period, the team attempted to manage 51 schizophrenics, 30 acute psychotics, 27 M. D. P. and 268 epileptics in the community with minimum number of drugs. The experiences and outcome of this attempt is presented and discussed here. PMID- 22065016 TI - 6-Meth-oxy-2-methyl-1-phenyl-1H-indole-3-carbonitrile. AB - In the title compound, C(17)H(14)N(2)O, the dihedral angle between the indole ring system and the phenyl ring is 64.48 (7) degrees . The crystal packing features weak C-H?pi inter-actions. PMID- 22065017 TI - 3,3,4,4-Tetra-fluoro-1-[2-(3,3,4,4-tetra-fluoro-pyrrolidin-1-yl)phen yl]pyrrolidine. AB - The asymmetric unit of the title compound, C(14)H(12)F(8)N(2), contains one tetra fluoro-pyrrolidine system and one half-mol-ecule of benzene; the latter, together with a second heterocyclic unit, are completed by symmetry, with a twofold crystallographic axis crossing through both the middle of the bond between the C atoms bearing the heterocyclic rings and the opposite C-C bonds of the whole benzene mol-ecule. The pyrrolidine ring shows an envelope conformation with the apex at the N atom. The dihedral angle between the least-squares plane of this ring and the benzene ring is 36.9 (5) degrees . There are intra-molecular C-H?N inter-actions generating S(6) ring motifs. In the crystal structure, the mol ecules are linked by C-H?F inter-actions, forming chains parallel to [010]. PMID- 22065018 TI - Iowa Case Management for Rural Drug Abuse. AB - OBJECTIVE: The purpose of this research was to evaluate the effectiveness of a comprehensive, strengths-based model of case management for clients in drug abuse treatment. METHOD: 503 volunteers from residential or intensive outpatient treatment were randomly assigned to one of three conditions of Iowa Case Management (ICM) plus treatment as usual (TAU), or to a fourth condition of TAU only. All were assessed at intake and followed at 3, 6, and 12 months. RESULTS: Clients in all four conditions significantly decreased substance use by 3 months after intake and maintained most gains over time. However, the addition of ICM to TAU did not improve substance use outcomes. CONCLUSION: Overall, the addition of case management did not significantly improve drug treatment as hypothesized by both researchers and clinicians. Some results were mixed, possibly due to the heterogeneous sample, wide range of case management activities, or difficulty retaining participants over time. PMID- 22065019 TI - catena-Poly[[aqua-[1,4-bis-(1H-imidazol-4-yl)benzene]cadmium]-MU(3)-5-methyl isophthalato]. AB - In the title coordination polymer, [Cd(C(9)H(6)O(4))(C(12)H(10)N(4))(H(2)O)](n), the Cd(II) atom has a NO(6) donor set and is coord-inated by five carboxyl-ate O atoms from three different 5-methyl-1,3-phenyl-enediacetate (pda(2-)) anions, one O atom from a water mol-ecule and one N atom from a 1,4-bis-(1H-imidazol-4 yl)benzene (L) ligand, displaying a highly distorted penta-gonal-bipyramidal geometry. Each pda(2-) anion acts as a MU(3)-bridge, linking Cd(II) atoms to form one-dimensional slabs extending parallel to [010]. In the crystal, adjacent mol ecules are linked through N-H?N and N-H?O hydrogen bonds into a three-dimensional network. PMID- 22065020 TI - Dichloridotetra-kis-(diniconazole)nickel(II). AB - In the title compound, [NiCl(2)(C(15)H(17)Cl(2)N(3)O)(4)], the Ni atom lies on an inversion center and has an axially extended trans-NiCl(2)N(4) octa-hedral geometry arising from its coordination by four diniconazole [systematic name: (E) (RS)-1-(2,4-dichloro-phen-yl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pent-1-en-3 ol] ligands and two chloride ions. In the crystal, O-H?Cl hydrogen bonds link the mol-ecules into [100] chains. PMID- 22065021 TI - 4-[2-(2-Meth-oxy-phen-yl)hydrazinyl-idene]-3-methyl-5-oxo-4,5-dihydro-1H-pyrazole 1-carbothio-amide. AB - In the title mol-ecule, C(12)H(13)N(5)O(2)S, a bifurcated intra-molecular N H?O(O) hydrogen bond forms two S(6) ring motifs. The benzene ring forms a dihedral angle of 14.36 (11) degrees with the pyrazole ring. In the crystal, pairs of N-H?S hydrogen bonds form centrosymmetric dimers, generating R(2) (2)(8) ring motifs, which stack along the b axis. PMID- 22065022 TI - 3-(2-Bromo-phen-yl)thia-zolo[3,2-a]benzimidazole. AB - The title compound, C(15)H(9)BrN(2)S, was prepared by the reaction of 1-bromo-2 (2,2-dibromo-vin-yl)benzene with 1H-benzo[d]imidazole-2(3H)-thione. The thia zolo[3,2-a]benz-imidazole fused-ring system is nearly planar, the maximum atomic deviation being 0.049 (4) A. This mean plane is oriented at a dihedral angle of 71.55 (17) degrees with respect ot the bromo-phenyl ring. pi-pi stacking is observed in the crystal structure, the centroid-centroid distance between the thia-zole and imidazole rings of adjacent mol-ecules being 3.582 (2) A. PMID- 22065023 TI - Dichlorido(eta-cyclo-octa-1,5-diene)bis-(propane-nitrile-kappaN)ruthenium(II). AB - In the title complex, [RuCl(2)(C(8)H(12))(C(3)H(5)N)(2)], the metal ion is coordinated to both double bonds of the cyclo-octa-1,5-diene ligand, two chloride ions (in cis positions) and two N-atom donors from two propane-nitrile mol-ecules that complete the coordination sphere for the neutral complex. The coordination around the Ru(II) atom can thus be considered as octa-hedral with slight trigonal distortion. PMID- 22065024 TI - Bis(MU-2-phenyl-quinoline-4-carboxyl-ato)bis-[aqua-(1,10-phenanthroline)(2-phenyl quinoline-4-carboxyl-ato)manganese(II)] dihydrate. AB - In the centrosymmetric dinuclear title complex, [Mn(2)(C(16)H(10)NO(2))(4)(C(12)H(8)N(2))(2)(H(2)O)(2)].2H(2)O, the Mn(II) cation is in a distorted octa-hedral coordination geometry defined by two N atoms from a 1,10-phenanthroline ligand, one water O atom and three O atoms from three 2 phenyl-quinoline-4-carboxyl-ate anions. A pair of 2-phenyl-quinoline-4-carboxyl ate anions bridge two Mn cations, forming the dinuclear mol-ecule. An intra moleculr O-H?O hydrogen bond occurs. Inter-molecular O-H?O and O-H?N hydrogen bonds are present in the crystal structure. PMID- 22065025 TI - N-(2-Nitro-oxyeth-yl)picolinamide. AB - In the title mol-ecule, C(8)H(9)N(3)O(4), the amide group is involved in the formation of an intra-molecular N-H?N hydrogen bond. In the crystal, mol-ecules related by translation along the a axis are linked into chains via weak inter molecular C-H?O inter-actions. PMID- 22065026 TI - Bis(guanidinium) cyananilate. AB - The asymmetric unit of the title compound, 2CH(6)N(3) (+).C(8)N(2)O(4) (2-), contains one half of a centrosymmetric 2,5-di-cyano-3,6-dioxocyclo-hexa-1,4-diene 1,4-diolate (cyananil-ate) anion and one guanidinium cation, which are connected by N-H?O and N-H?N hydrogen bonds into a three-dimensional network. PMID- 22065027 TI - Narrow band imaging and high definition television in the endoscopic evaluation of upper aero-digestive tract cancer. AB - Narrow band imaging and high definition television are recent innovations in upper aero-digestive tract endoscopy. Aim of this prospective, non-randomized, unblinded study was to establish the diagnostic advantage of these procedures in the evaluation of squamous cell cancer arising from various upper aero-digestive tract sites. Between April 2007 and January 2010, 444 patients affected by upper aero-digestive tract squamous cell cancer, or previously treated for it, were evaluated by white light and narrow band imaging +/- high definition television endoscopy, both in the pre-/intra-operative setting and during follow-up. Tumour resection was performed taking into account narrow band imaging and high definition television information to obtain histopathologic confirmation of their validity. Endoscopic and pathologic data were subsequently matched to obtain sensitivity, specificity, positive, negative predictive values, and accuracy. Overall, 110 (25%) patients showed adjunctive findings by narrow band imaging +/- high definition television when compared to standard white light endoscopy. Of these patients, 98 (89%) received histopatological confirmation. The sensitivity, specificity, positive, negative predictive values, and accuracy for white light high definition television were 41%, 92%, 87%, 82%, and 67%, for narrow band imaging alone 75%, 87%, 87%, 74%, and 80%, and for narrow band imaging-high definition television 97%, 84%, 88%, 96%, and 92%. The highest diagnostic gain was observed in the oral cavity and oropharynx (25%). Narrow band imaging and high definition television were of value in the definition of superficial tumour extension, and in the detection of synchronous lesions in the pre-/intra operative settings. These technologies also played an important role during post treatment surveillance for early detection of persistences, recurrences, and metachronous tumours. PMID- 22065028 TI - 7-Benzyl-3-(4-fluoro-phen-yl)-2-(pyrrol-idin-1-yl)-5,6,7,8-tetra-hydro pyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-one. AB - In the title compound, C(26)H(25)FN(4)OS, the thienopyrimidine fused-ring system is close to planar (r.m.s. deviation = 0.066 A), with a maximum deviation of 0.1243 (17) A for the N atom adjacent to the carbonyl group. This ring system forms dihedral angles of 67.5 (1) and 88.9 (1) degrees with the adjacent six membered rings. Inter-molecular C-H?O hydrogen bonding and C-H?pi inter-actions help to stabilize the crystal structure. PMID- 22065029 TI - 4-(3-Methyl-4,5-dihydro-1H-benzo[g]indazol-1-yl)benzene-sulfonamide. AB - In the title compound, C(18)H(17)N(3)O(2)S, the aromatic ring bearing the sulfamide unit is aligned at 61.65 (1) degrees with respect to the pyrrole ring; its amino group forms N-H?N and N-H?O hydrogen bonds to neighboring mol-ecules, generating sheets in the ac plane. PMID- 22065030 TI - 2-(4-Chloro-phen-yl)-2-oxoethyl 4-hy-droxy-benzoate. AB - The title compound, C(15)H(11)ClO(4), consists of a chloro-benzene ring and a phenol ring which are linked together by a 1,4-dioxo-2-oxabutane-1,4-diyl group. The dihedral angle between the chloro-benzene and phenol rings is 65.70 (11) degrees . In the crystal, inter-molecular O-H?O hydrogen bonds link the mol ecules into chains along [010]. PMID- 22065031 TI - Heart failure: a problem of our age. PMID- 22065032 TI - Thyroid dysfunction and long-term outcome during and after interferon-alpha therapy in patients with chronic hepatitis C. AB - INTRODUCTION: Thyroid dysfunction (TD) is a well-established adverse effect in chronic hepatitis C virus (HCV)-infected patients, treated with interferon-alpha (IFN-alpha), with or without ribavirin. However, the long-term outcome is not well-studied. The purpose of this study was to estimate the prevalence and long term outcome of TD after HCV-therapy. MATERIALS AND METHODS: Retrospective analysis of 109 HCV-treated patients (for 6 to 12 months, according to HCV genotype), for the period 1996 to 2008. Thyroid function tests were performed every 3 months during therapy and after discontinuation (3 months to 12 years). Routine laboratory tests and virological assessment were performed according to generally accepted practice. RESULTS: TD was observed in 26 patients (23.85%). The positive and negative predictive value for thyroid autoantibodies (ATA) was 80% and 72.7%, respectively. Relative risk for those with positive ATA was 2.9 (95% CI: 1.6 to 5.3, P = 0.014). The median duration of TD was 12.0 months (min: 3; max: 132). The median follow-up period for the patients with TD was 25.5 months (min: 12; max: 144). Finally, 15 patients developed permanent TD (57.69%), compared to 11 with temporary TD (42.31%). Sex is a risk factor for TD, as there were more females than males affected (P = 0.011). Genotype, viral load, time of HCV-exposure prior to therapy, and virological response did not differ between patients with and without TD. CONCLUSION: TD among HCV-treated patients was more frequent than usually reported, with >50% developing permanent TD. ATA status may play a role in estimating the risk of subsequent TD. Women appear to be more vulnerable to TD than men. PMID- 22065033 TI - Renal cell carcinoma in young patients is associated with poorer prognosis. AB - INTRODUCTION: Renal cell carcinoma (RCC) in young patients is uncommon but thought to represent a distinctive clinical entity from older patients with different clinico-pathologic features and outcomes. We evaluated the association of age at the time of diagnosis with pathological staging, histological parameters, disease recurrence and overall survival (OS) following radical or partial nephrectomy for non-metastatic RCC in native kidneys. MATERIALS AND METHODS: A retrospective review of 316 patients with RCC after nephrectomy at a single institution between January 2001 and June 2008 was performed. Eligible patients included all histologically proven primary non-metastatic RCC treated by radical or partial nephrectomy. They were categorised into group A (<= 40 years at diagnosis) and B (> 40 years). Differences in clinical parameters were analysed using the Mann Whitney U test. The prognostic potential of age at diagnosis was evaluated using Cox proportional hazards regression. Survival was estimated using the Kaplan Meier method. RESULTS: There were 33 patients in group A and 283 patients in group B. There were more non-clear cell tumours in the younger group (30% vs 14%, P <0.05). No statistical differences were found in the stage and grade of both groups. At a median follow-up time of 41 months, the younger group had a higher metastatic rate (18% vs 10.5%, P <0.05), lower 5-year cancer-specific survival (82% vs 98%, P <0.05) and lower 5-year OS (82 % vs 95%, P <0.05). CONCLUSION: Younger patients were more likely to have non-clear cell RCC with higher disease recurrence and lower OS. They should not be assumed to have similar features and outcomes as screen-detected early RCC in older patients. PMID- 22065034 TI - Acute pyelonephritis and renal abscesses in adults--correlating clinical parameters with radiological (computer tomography) severity. AB - INTRODUCTION: The aim of this study is to evaluate the correlations between clinical and biochemical parameters with radiological severity of CT diagnosed acute pyelonephritis (APN) and renal abscesses, thereafter defining clinical predictors to identify patients with severe APN or renal abscesses. MATERIALS AND METHODS: The inpatient medical records of all patients diagnosed with APN or renal abscesses admitted over one year were reviewed. Patients with CT imaging performed were classified into 3 groups--mild APN, severe APN and renal abscesses. Clinical and biochemical parameters were correlated with radiological severity. RESULTS: One hundred and thirty patients were included in the study. Male gender, older age, presence of diabetes mellitus and unobstructing renal stones were significantly associated with severe APN or renal abscesses. Clinical and biochemical parameters that were associated with more severe disease include a higher leucocyte count and C-reactive proteins, left neutrophil shift, thrombocytosis or thrombocytopenia, low serum albumin, acute renal impairment and bacteremia. The percentage of patients had positive urine and blood cultures were 40.8% and 30.7% respectively. Of these patients, 97.9% had severe APN or renal abscesses on CT imaging had diabetes mellitus (DM), hypotension, acute renal failure or leucocyte count of >20K. CONCLUSION: Our study showed a good correlation between clinical and radiological severity in adult patients with APN and renal abscesses. Patients with severe APN or renal abscesses were likely to be diabetics presenting with hypotension, acute renal impairment and a leucocyte count of greater than 20K. PMID- 22065035 TI - Thoracic endovascular aortic repair: a local single institution experience. AB - INTRODUCTION: The purpose of this retrospective study was to evaluate the short- to mid-term results of the endovascular repair of thoracic aortic disease and to present an overview of our experience with thoracic endovascular aortic repair (TEVAR) in our institution. MATERIALS AND METHODS: A retrospective review of all patients who were treated and underwent TEVAR in our institution between August 2004 and November 2009 was conducted. RESULTS: Technical success was achieved in 100% of the patients and the 30-day mortality rate was 0%. Perioperative endoleak was visualised at the end of the procedure in 4 patients. Secondary endoleak was observed in 2 patients. Mean hospital length of stay post-TEVAR was 15.4 days. Postoperative major complications were observed in 4 patients. The 30-day mortality rate was 0%, with 2 mortalities (11.1%) during the followup period. CONCLUSION: This study adds to the growing body of literature that support TEVAR as an effective procedure in the management of thoracic aortic diseases and reflects its feasibility in our population. Further technical advancement in stent grafts, careful selection of patients and standardised peri-procedural care would contribute to further improvements in clinical outcomes. PMID- 22065036 TI - MELAS associated pathological hyperemotionalism: a case report. PMID- 22065037 TI - Mismatched bone marrow transplantation for severe aplastic anaemia after liver transplantation for associated acute liver failure. PMID- 22065038 TI - Anticonvulsant hypersensitivity syndrome secondary to lamotrigine mimicking a septic episode. PMID- 22065039 TI - A case of myeloid sarcoma with unusually extensive and rapidly progressive skin manifestations. PMID- 22065040 TI - Giant subphrenic abscess: a rare complication of laparoscopic-assisted vaginal hysterectomy. PMID- 22065041 TI - Acute upper airway obstruction secondary to gunshot injury splitting cervical vertebra. PMID- 22065042 TI - A rare mediastinal tumour with spinal cord involvement in an adult. PMID- 22065043 TI - 2-Azido-methyl-3-methyl-1-phenyl-sulfonyl-1H-indole. AB - In the title compound, C(16)H(14)N(4)O(2)S, the plane of the indole ring is twisted by 70.4 (2) degrees with respect to the plane of the azidomethyl- substituent. As a result of the electron-withdrawing character of the phenyl sulfonyl groups, the N-C bond lengths are slightly longer than the anti-cipated value of approximately 1.355 A for an N atom with a planar configuration. The indole ring is essentially planar, with a maximum deviation of 0.0296 A. The azide group is almost linear, the N-N-N angle being 171.4 (3) degrees . The methyl group on the azide-substituted C atom is in a flagpole position. The phenyl ring of the sulfonyl substituent makes a dihedral angle of 87.07 (10) degrees with the best plane of the indole moiety. The crystal packing is stabilized by inter-molecular C-H?O inter-actions, which link the mol-ecules into infinite chains running parallel to the b axis. The crystal packing is further stabilized by C-H?pi inter-actions. PMID- 22065044 TI - Poly[[(2,2'-bipyridine)(MU(3)-7-oxabicyclo-[2.2.1]heptane-2,3-dicarboxyl ato)cadmium] monohydrate]. AB - The title compound, {[Cd(C(8)H(8)O(5))(C(10)H(8)N(2))].H(2)O}(n), was obtained by the reaction of cadmium acetate with 2,2'-bi-pyridine and 7-oxabicyclo (2.2.1)heptane-2,3-dicarb-oxy-lic anhydride. The Cd(II) atom is seven-coordinated in a distorted penta-gonal-bipyramidal configuration, defined by five O atoms from the carboxyl-ate groups of three 7-oxabicyclo-[2.2.1]heptane-2,3-dicarboxyl ato ligands and two N atoms from the 2,2'-bipyridine ligand. Two O atoms link two Cd(II) atoms, forming a dinuclear center: the Cd-O-Cd bridging angle is 110.19 (6) degrees . The polymeric structure extends along [100] and is linked by inter molecular O-H?O hydrogen bonds involving the solvent water molecule. Extensive pi pi stacking exists between 2,2-bypiridine ligands along [010] with centroid centroid distance of 3.650 (2) A PMID- 22065045 TI - Context-dependent motor skill and the role of practice. AB - Research has shown that retrieval of learned information is better when the original learning context is reinstated during testing than when this context is changed. Recently, such contextual dependencies have also been found for perceptual-motor behavior. The current study investigated the nature of context dependent learning in the discrete sequence production task, and in addition examined whether the amount of practice affects the extent to which sequences are sensitive to contextual alterations. It was found that changing contextual cues but not the removal of such cues-had a detrimental effect on performance. Moreover, this effect was observed only after limited practice, but not after extensive practice. Our findings support the notion of a novel type of context dependent learning during initial motor skill acquisition and demonstrate that this context-dependence reduces with practice. It is proposed that a gradual development with practice from stimulus-driven to representation-driven sequence execution underlies this practice effect. PMID- 22065046 TI - Expression of antigen processing and presenting molecules in brain metastasis of breast cancer. AB - Defects in human leukocyte antigen class I antigen processing machinery (APM) component expression can have a negative impact on the clinical course of tumors and the response to T cell-based immunotherapy. Since brain metastases of breast cancer are of increasing clinical significance, the APM component expression levels and CD8(+) T cell infiltration patterns were analyzed in primary breast and metastatic brain lesions of breast cancer by immunohistochemistry. Comparison of unpaired 50 primary and 33 brain metastases showed lower expression of beta2 microglobulin, transporter associated with antigen processing (TAP) 1, TAP2 and calnexin in the brain lesions. Although no significant differences were found in APM component scores between primary breast and brain lesions in 15 paired cases, primary breast lesions of which patients eventually developed brain metastases showed lower levels of beta2-microglobulin, TAP1 and calnexin compared with breast lesions without known brain metastases. The extent of CD8(+) T cell infiltration was significantly higher in the lesions without metastasis compared with the ones with brain metastases, and was positively associated with the expression of TAP1 and calnexin. Furthermore, mouse tumor cells stably transfected with silencing hairpin (sh)RNA for TAP1 demonstrated a decreased susceptibility to cytotoxic T lymphocytes in vitro and enhanced spontaneous brain metastasis in vivo. These data support the functional significance of TAP1 expression in tumor cells. Taken together, our data suggest that patients with low or defective TAP1 or calnexin in primary breast cancers may be at higher risks for developing brain metastasis due to the defects in T cell-based immunosurveillance. PMID- 22065047 TI - Regulatory dendritic cells in the tumor immunoenvironment. AB - The tumor microenvironment is a pivotal factor in tumorigenesis, and especially in progression, as the pathogenesis of cancer critically depends on the complex interactions between various microenvironmental components. A key component of the tumor immunoenvironment is the infiltration of immune cells, which has been proven to play a dual role in tumor growth and progression. This Janus two-faced function of the tumor immunoenvironment is seen in tumor infiltration by T cells, which correlates with improved patient survival, but also with the homing of multiple subsets of immunoregulatory cells that inhibit the antitumor immune response. Regulatory dendritic cells (regDCs) have recently been shown to be induced by tumor-derived factors and represent a new and potentially important player in supporting tumor progression and suppressing the development of antitumor immune responses. Our recent data reveal that different tumor cell lines produce soluble factors that induce polarization of conventional DCs into regDCs, both in vitro and in vivo. These regDCs can suppress the proliferation of pre-activated T cells and are phenotypically and functionally different from their precursors as well as the classical immature conventional DCs. Understanding the biology of regDCs and the mechanisms of their formation in the tumor immunoenvironment will provide a new therapeutic target for re-polarizing protumorigenic immunoregulatory cells into proimmunogenic effector cells able to induce and support effective antitumor immunity. PMID- 22065048 TI - A rebuttal to the potential anti-tumour benefit of Helicobacter pylori-induced neutrophil-activating protein. PMID- 22065049 TI - Visualization of dual coronary artery fistulae drainage to the right ventricle by transthoracic echocardiography. AB - Coronary artery fistula is a rare abnormality of coronary circulation. It is mostly congenital but acquired forms can also occur. Fistulae are usually asymptomatic and can sometimes be visualized during cardiac imaging such as transthoracic echocardiogram, cardiac magnetic resonance imaging, coronary computed tomography angiography and coronary angiography. PMID- 22065050 TI - 1-[(Z)-8-(4-Chlorophenoxy)-3-(2,4-di-fluorophenyl)-4-oxaocta-2-en-2-yl]-1H-1,2,4 triazol-4-ium nitrate. AB - In the title compound C(21)H(21)ClF(2)N(3)O(2) (+).NO(3) (-), the triazole ring makes dihedral angles of 40.7 (3) and 30.2 (4) degrees with the 4-chloro-pheny and 2,4-difluoro-phenyl rings, respectively. The cation adopts a Z-configuration about the C=C double bond which links the triazole ring to the 4-chloro-phen-oxy unit via a but-yloxy chain. In the crystal, the cations and the anions are linked by N-H?O, C-H?O and C-H?F hydrogen bonding. PMID- 22065051 TI - The stratum corneum revisited: a new understanding of its role in healthy and diseased skin. Introduction. PMID- 22065052 TI - Clinical relevance of maintaining the structural and functional integrity of the stratum corneum: why is it important to you? PMID- 22065053 TI - Managing epidermal barrier function in the treatment of dermatoses. PMID- 22065054 TI - Expression of coagulation factors and their receptors in tumor tissue and coagulation factor upregulation in peripheral blood of patients with cerebral carcinoma metastases. AB - BACKGROUND: Patients with malignancies often suffer from thrombembolic events that complicate the course of cancer disease and reduce the patients' quality of life or shorten the survival time in severe cases. This phenomenon is also known for patients with primary or secondary brain tumors; but the reasons are not identified. METHODS: We performed a prospective case-controlled study of patients with brain metastases but without any active peripheral tumor site. Blood of patients was collected perioperatively and investigated for coagulation factor activities. Moreover, we analyzed the expression of coagulation factors and their receptors within the tumor material of brain metastases from clear-cell renal cell carcinomas and small-cell carcinomas of the lung. RESULTS: Here, we show that even patients without an active peripheral tumor disease that means without any tumor masses outside the central nervous system after anticancer treatment by surgery, radiation therapy, or chemotherapy but with symptomatic brain metastasis develop an increased systemic activation of multiple coagulation factors. The pro coagulatory state is expressed preoperatively, but also can be observed in the early postoperative period. Additionally to that, intracerebral metastases of clear-cell renal cell carcinomas and of small-cell carcinomas of the lung express prothrombin, thrombin, factor X, and the protease-activated receptors type 1, 2, 3, and 4. CONCLUSIONS: These observations support the hypothesis of a link between the hemostatic system in the periphery and the malignant tumor disease even when the tumor is an intracerebral metastasis and the affected patient currently is free of a systemically active tumor. The results of this study support the hypothesis that the concerted action of coagulation factors and their receptors within the metastasis tissue itself and the systemic coagulation system could control the malignant behavior of tumor disease and make larger prospective trials mandatory. PMID- 22065055 TI - Management of drug-resistant spinal tuberculosis with a combination of surgery and individualised chemotherapy: a retrospective analysis of thirty-five patients. AB - PURPOSE: Drug-resistant tuberculosis is a major public-health concern globally and can be difficult to manage clinically. Spinal tuberculosis is the most common manifestation of extrapulmonary tuberculosis. However, there have been few reports on the topic of drug-resistant spinal tuberculosis. The aim of this study was to investigate the clinical characteristics and drug susceptibility patterns and the outcomes of management with a combination of surgery and individualised chemotherapy, for drug-resistant spinal tuberculosis. METHODS: We retrospectively analysed 35 patients with drug-resistant tuberculous spondylitis. After surgery, individualised chemotherapy was tailored for each patient according to the drug resistance profile and previous history of chemotherapy. The patients were followed up clinically and radiologically for an average period of 35.8 months. RESULTS: Among 35 drug-resistant spinal tuberculosis cases, 13 were retreatment cases. Twelve were multi-drug resistant tuberculosis (MDR-TB), and 23 were non MDR-TB. The patients with MDR-TB and non-MDR-TB had undergone previous chemotherapy for an average of 14.50 +/- 2.00 (0-60) months and 4.56 +/- 1.54 (0 74) months, respectively. A total of 32 cases underwent open operations, and the other three had percutaneous drainage and local chemotherapy. Patients received individualised chemotherapy for an average of 23.6 months postoperatively. Local recurrence was observed in six patients. Thirty-three patients had been cured at the final follow-up, and the other two were still receiving chemotherapy. CONCLUSIONS: Drug-resistant tuberculous spondylitis is mainly acquired through previous irregular chemotherapy and the spreading of drug-resistant strains. Management with a combination of surgery and individualised chemotherapy is feasible in the treatment of severe complications and the prevention of acquired drug resistance. PMID- 22065057 TI - 5-(4-Fluoro-phen-yl)-3-methyl-sulfanyl-2-phenyl-1-benzofuran. AB - In the title compound, C(21)H(15)FOS, the dihedral angle between the mean plane of the benzofuran fragment and the mean planes of the pendant 4-fluoro-benzene and phenyl rings are 31.72 (6) degrees and 32.51 (6) degrees , respectively. In the crystal, the mol-ecules are linked by weak C-H?pi inter-actions. The crystal studied was a merohedral twin with a 0.62 (9):0.38 (9) domain ratio. PMID- 22065058 TI - Transurethral prostate biopsy before radical cystectomy remains clinically relevant for decision-making on urethrectomy in patients with bladder cancer. AB - BACKGROUND: This study retrospectively evaluated the clinical relevance of transurethral prostate biopsy (TUPB) before radical cystectomy by comparing the pathology of prostatic urethra biopsy specimens with that of cystectomy specimens. METHODS: Of 294 patients who underwent cystectomy and urinary diversion, 101 men with preoperative TUPB were included in this study. For these patients, if the result of TUPB was positive for urothelial carcinoma, we performed urethrectomy as a rule. If it was negative, we presented the option of urethral preservation and decided the final type of urinary reconstruction. The sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of TUPB were assessed, and we investigated the number of final urethral recurrences. We also tried to identify which clinical and pathological findings by TUPB most accurately predicted the disease remaining in the prostate of cystectomy specimens. RESULTS: Of the 25 patients with positive TUPB, 18 had disease in the prostatic urethra or stroma of cystectomy specimens. There were 3 patients with negative TUPB but with involvement of the prostate in cystectomy specimens. Thus, TUPB achieved 86% sensitivity, 91% specificity, 72% PPV, and 96% NPV. Two patients (1.9%) had urethral recurrence in this period. Among the findings for TUPB, non-papillary tumors most accurately predicted the disease in the prostate of cystectomy specimens. CONCLUSIONS: TUPB achieved a high NPV and the urethral recurrence rate was acceptable. If TUPB was negative, patients could have chance urethral preservation. Thus, our clinical decision for urethrectomy based on the result of TUPB is still useful. PMID- 22065059 TI - Development of a light microscopy stain for the sclerites of Gyrodactylus von Nordmann, 1832 (Monogenea) and related genera. AB - Recent developments in semi-automated identification techniques and the increasing ability to rapidly access digital images and taxonomic descriptions offer to increase the range of individuals capable of performing taxonomic identifications. The present study details methodological approaches undertaken in developing a dedicated stain for the visualisation of monogenean haptoral skeletal elements and reproductive sclerites. The histochemical protocols centre around the use of fluorescent dyes and standard light and laser scanning confocal microscopy to support studies of the functional morphology of these hard structures in small, relatively uncompressed specimens, making these structures more amenable to semi-automated analysis and identification techniques. Staining of the sclerites was achieved using a tissue digestion step to remove the tegument and tissues enclosing the sclerites and then staining them in situ with 40 mM chromothrope 2R (C2R) containing 3 mM phosphotungstic acid (PTA) and 0.5% acetic acid (AA) at room temperature for up to 2 days. Visualisation of the armature of the male copulatory organ of warm water Gyrodactylus species was achieved using 40 mM C2R containing 3 mM PTA for 3 days, whilst cold water species were best stained in 6.4 mM C2R for 1 day without an NaOH pre-treatment. The developed techniques allow for good visualisation of the skeletal elements in a number of monogenean groups and promise to assist the preparation and identification/description of specimens. The 2D/3D digital images of specimens prepared in this manner should provide a useful resource for taxonomists and others needing material to assist specimen identification. PMID- 22065060 TI - Diagnosis of visceral leishmaniasis: developments over the last decade. AB - Diagnostic parameters for visceral leishmaniasis (VL), a potentially fatal parasitic disease caused by Leishmania donovani, have been redefined in the last decade with the development of serological and molecular tests, though a definitive diagnosis still banks on the century-old parasitological methods in many areas. Recombinant antigens have improved performance of serodiagnostic methods. Serology-based tests, rk39 antigen dipstick, and direct agglutination test commonly employed in the field are highly sensitive methods, however, fail to distinguish past infections. Molecular approaches have become increasingly relevant due to remarkable sensitivity, specificity, and flexibility in choice of samples. Quantitative polymerase chain reaction is a highly sensitive and specific tool used in referral labs for detection/assessment of parasite load in VL patients and subsequently in monitoring treatment response to antileishmanial agents. The method displays potential to provide threshold for distinguishing asymptomatics in endemic areas. Currently, improvement in VL diagnostics is required for successful decentralized (point-of-care) testing in field conditions and to detect VL-HIV co-infection. Techniques such as loop-mediated isothermal amplification offer a reliable molecular diagnostic method for field application. The diagnosis based on bioanalytics/biosensors promise frontiers for point-of care VL detection after adequate standardization. This review summarizes the recent developments in VL diagnostics, drawing attention towards the need for standardization of the diagnostics across the affected regions. PMID- 22065061 TI - Essential oils of indigenous in Greece six Juniperus taxa: chemical composition and larvicidal activity against the West Nile virus vector Culex pipiens. AB - The chemical composition of 14 essential oils (EOs), obtained from various parts (leaves, fruits, wood) of the six indigenous in Greece Juniperus family taxa, was determined by GC and GC/MS analysis. The insecticidal properties of these EOs were evaluated against Culex pipiens L. larvae of 3rd and early 4th instars, in order to delineate the relationship between the phytochemical content of the EOs and their larvicidal activities. The analytical data indicated that the EOs mainly consisted of monoterpenes, mostly cyclic and only occasionally aliphatic, and to a lesser percent, of diterpenes. The larvicidal bioassays against C. pipiens larvae revealed that the most active EO was derived from the wood of Juniperus drupacea and contains mainly non-oxygenated monoterpenes and a significant amount of diterpenes, displaying the highest chemodiversity. Its initial LC(50) value was 26.47 mg L(-1). On the contrary, the EO isolated from J. phoenicea berries, which consisted of monoterpenes (non-oxygenated, cyclic), was the less active displaying an LC(50) value of 96.69 mg L(-1). In respect to the contained phytochemicals, myrcene was assayed as the most toxic, displaying an LC(50) value of 33.83 mg L(-1), while the four isomers of pinene abundant in all EOs were less active exhibiting LC(50) values ranging from 70.40 to 94.88 mg L( 1). Results herein reveal that the EOs isolated from the studied Juniperus family taxa represent an inexpensive source of natural mosquito control mixtures. PMID- 22065062 TI - Insecticidal potency of bacterial species Bacillus thuringiensis SV2 and Serratia nematodiphila SV6 against larvae of mosquito species Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. AB - The tremendous worldwide efforts to isolate novel mosquito larvicidal bacteria with improved efficacy present significant promise to control vector-borne diseases of public health importance. In the present study, two native bacterial isolates, Bacillus thuringiensis (Bt SV2) and Serratia species (SV6) were evaluated for mosquito larvicidal potential against the early fourth instar larvae of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus with reference to B. thuringiensis subsp. israelensis (Bti) H 14. The native Gram positive, spore-forming Bt SV2 isolate showed 100% mortality against early fourth instars of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus, in parallel to Bti H14 strain. After 24 h, Bt SV2 showed 98%, 89%, and 80.67%, and Bti H14 showed 92%, 98.33%, and 60% mortality against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus, respectively. Serratia SV6 showed highest activity against Culex quinquefasciatus (100%) followed by Anopheles stephensi (95%) and Aedes aegypti (91%) after 48 h of exposure. The Gram-negative Serratia SV6 showed delayed toxicity compared to Bti H14 and Bt SV2 against early fourth instars of Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. The relative mortality of all treatments after 12-h exposures showed the varied toxicity with respect to exposure time, bacterial treatment, and mosquito species. Genetic relatedness of the strains was confirmed on the basis of phylogenetic reconstructions based on alignment of 16S rRNA gene sequences which indicated a strong clustering of the strain SV2 with B. thuringiensis and the strain SV6 with Serratia nematodiphila. In conclusion, the native isolate B. thuringiensis SV2 showed significant toxicity while Serratia SV6 showed less and delayed toxicity against several mosquito species compared with BtiH14. They may be used as novel bacterial insecticidal agents in mosquito vector-borne disease control. To our knowledge, this is the first report on mosquito larvicidal potential of Serratia species. PMID- 22065063 TI - Larvicidal activity of medicinal plant extracts and lignan identified in Phryma leptostachya var. asiatica roots against housefly (Musca domestica L.). AB - Medicinal plant extracts from 27 plant species in 20 families were tested for their larvicidal activity against housefly, Musca domestica (L.). Responses varied with plant material and concentration. Among plant species tested, Phryma leptostachya var. asiatica showed 100% larvicidal activity against M. domestica at 10 mg/g concentration. Larvicidal activities of Atractylodes japonica, Saussurea lappa, Asiasarum sieboldi, and Gleditsia japonica var. koraiensis were 89.3%, 85.3%, 93.3%, and 96.6% at 10 mg/g concentration, respectively. Extracts of Prunus persica, Curcuma longa, and Paeonia moutan produced moderate activity. Larvicidal activity of other plant extracts was less than 50%. Among test plant species, P. leptostachya var. asiatica showed the most potent larvicidal activity. The active constituent of P. leptostachya var. asiatica roots was identified as the leptostachyol acetate by spectroscopic analysis. The LC(50) values of leptostachyol acetate against M. domestica larvae were 0.039 mg/g. Naturally occurring medicinal plant extracts and P. leptostachya var. asiatica root-derived compounds merit further study as potential housefly larval control agents or lead compounds. PMID- 22065064 TI - [Prognosis and quality of life after decompressive hemicraniectomy: a nationwide survey in Germany on the attitudes held by doctors and nurses]. AB - BACKGROUND: Decompressive hemicraniectomy reduces mortality in patients with space-occupying MCA infarction. Quality of life in surviving patients is discussed controversially. We assessed attitudes of neurologists and nurses providing care to this patient group towards decompressive hemicraniectomy. METHODS: A postal questionnaire on attitudes and opinions on prognosis and quality of life after decompressive hemicraniectomy was returned by 280 neurologists and 166 nurses from tertiary care centers throughout Germany. RESULTS: In both groups of professionals, estimates of the probability of survival after decompressive hemicraniectomy and the resulting degree of disability were consistent with results of clinical outcomes studies. Only 9% of the nurses and 33% of the physicians assumed that the majority of survivors achieve an acceptable quality of life; 58% of physicians and 32% of nurses would suggest decompressive hemicraniectomy to their nearest relative. Under the assumption of an uncertain outcome, 61% of physicians and 22% of nurses would agree to decompressive hemicraniectomy. In both professional groups, agreement for surgery increases when scenarios with a more favorable outcome were proposed [modified Rankin Scale (mRS) 2-5)]. If an outcome of 4 on the mRS is proposed, indicating moderately severe disability, only a minority favored decompressive hemicraniectomy (25% of doctors and 8% of nurses). CONCLUSIONS: Despite a realistic assessment of prognosis after decompressive hemicraniectomy, a majority of respondents estimated the quality of life of survivors as unsatisfactory. Nurses had a more pessimistic attitude towards decompressive hemicraniectomy. The majority of respondents consider an outcome of 4 on the mRS as unacceptable. PMID- 22065065 TI - 2-Hy-droxy-N-(4-methyl-phen-yl)benzamide. AB - In the crystal structure of the title compound, C(14)H(13)NO(2), the mol-ecules are approximately planar, the r.m.s. deviation for all non-H atoms being 0.0435 A; the dihedral angle between the two rings is 3.45 (12) degrees . The planarity is accounted for in terms of the presence of intra-molecular N-H?O and C-H?O hydrogen bonding, each of which completes an S(6) ring motif. The mol-ecules are stabilized in the form of supra-molecular chains extending along the crystallographic c axis due to inter-molecular O-H?O and C-H?O hydrogen bonding; each type leads to an R(2) (1)(6) ring motif. PMID- 22065066 TI - RNA splicing and debranching viewed through analysis of RNA lariats. AB - Intron lariat RNAs, created by pre-mRNA splicing, are sources of information on gene expression and structure. Although produced equivalently to their corresponding mRNAs, the vast majority of intron lariat RNAs are rapidly degraded. However, their levels are enhanced in cells deficient for RNA debranching enzyme, which catalyzes linearization of these RNAs, the rate limiting step in their degradation. Furthermore, RNA lariats are resistant to degradation by the 3' exonuclease polynucleotide phosphorylase (PNPase), providing a means to enrich for lariat RNAs. Working with the yeast Saccharomyces cerevisiae as a model organism, our goal was to develop novel combinations of methods to enhance the use of intron lariat RNAs as objects of study. Using RT PCR assays developed for detecting and quantifying specific lariat RNAs, we demonstrate the resistance of RNA lariats to degradation by PNPase and their sensitivity to cleavage by RNA debranching enzyme. We also employ sequential treatments with these two enzymes to produce characteristic effects on linear and lariat RNAs. We establish the utility of the methods for analyzing RNA debranching enzyme variants and in vitro debranching reactions and discuss several possible applications, including measuring relative rates of transcription and combining these methods with non-gene-specific RNA sequencing as a novel approach for genome annotation. In summary, enzymatic treatments that produce characteristic effects on linear and lariat RNAs, combined with RT-PCR or RNA sequencing, can be powerful tools to advance studies on gene expression, alternative splicing, and any process that depends on the RNA debranching enzyme. PMID- 22065067 TI - Genome-wide association analysis to identify chromosomal regions determining components of earliness in wheat. AB - The modification of flowering date is considered an important way to escape the current or future climatic constraints that affect wheat crops. A better understanding of its genetic bases would enable a more efficient and rapid modification through breeding. The objective of this study was to identify chromosomal regions associated with earliness in wheat. A 227-wheat core collection chosen to be highly contrasted for earliness was characterized for heading date. Experiments were conducted in controlled conditions and in the field for 3 years to break down earliness in the component traits: photoperiod sensitivity, vernalization requirement and narrow-sense earliness. Whole-genome association mapping was carried out using 760 molecular markers and taking into account the five ancestral group structure. We identified 62 markers individually associated to earliness components corresponding to 33 chromosomal regions. In addition, we identified 15 other significant markers and seven more regions by testing marker pair interactions. Co-localizations were observed with the Ppd-1, Vrn-1 and Rht-1 candidate genes. Using an independent set of lines to validate the model built for heading date, we were able to explain 34% of the variation using the structure and the significant markers. Results were compared with already published data using bi-parental populations giving an insight into the genetic architecture of flowering time in wheat. PMID- 22065068 TI - Role of Sp1 transcription factor in Interleukin-1-induced ADAMTS-4 (aggrecanase 1) gene expression in human articular chondrocytes. AB - Proinflammatory cytokines such as interleukin-1 beta (IL-1beta) stimulate cartilage extracellular matrix aggrecan degradation by aggrecanases or ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) during the pathogenesis of arthritis. Human aggrecanase-1 (ADAMTS-4) gene promoter contains at least one specificity protein-1 (Sp1)-transcription factor-binding site. We investigated the previously unknown role of Sp1 in the regulation of ADAMTS-4 gene expression in human articular chondrocytes. Mithramycin and WP631, the specific inhibitors of guanine cytosine (GC)-rich Sp1 DNA binding, partially suppressed IL-1-induced ADAMTS-4 expression and activity. Genetic inhibition of Sp1 by antisense oligonucleotide or by small interfering RNA (siRNA)-mediated Sp1 knockdown partially inhibited ADAMTS-4 induction by IL-1. Sense oligonucleotide and negative control siRNA had no effect. In contrast, cytomegalovirus promoter driven Sp1 overexpression further enhanced IL-1-induced ADAMTS-4 expression and activity. Constitutively expressed glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was not affected by any of the agents. These results provide pharmacological and genetic evidence for the importance of Sp1 in ADAMTS-4 gene regulation by IL-1. Thus, Sp1 could be potentially targeted to reduce arthritis associated cartilage aggrecan loss. PMID- 22065069 TI - Which clinical variables have the most significant correlation with quality of life evaluated by SF-36 survey in Croatian cohort of patient with ankylosing spondylitis and psoriatic arthritis? AB - The aim of our study was to assess clinical variables with the best correlation to quality of life (QOL) assessed by medical outcome survey Short-Form 36 (SF-36) in patients with spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). We analyzed the cohort of 54 patients (22 patients with PsA and 32 patients with AS), who filled the Croatian version of SF-36. For each type of arthritis, patients were clinically evaluated using the extensive list of clinical variables categorized into subjective and objective group. For AS patients, subjective and objective variables (spinal mobility measurements, clinical assessment of spinal pain, patient assessments of disease activity and pain) correlated mainly with the physical functioning concept of SF-36. Patients assessments of fatigue correlated with the energy/fatigue subscale, whereas patient assessment of enthesial pain correlated with the pain subscale. Correlations between clinical variables and SF-36 concepts of PsA patients showed more diverse distribution than for AS. Objective variables (spinal mobility measurements, a 76-joint score, clinical assessment of spinal pain) correlated with concepts concerning physical health and pain. Several subjective patient assessments correlated with energy/fatigue, emotional well-being, pain and general health subscales. Both patient and physician assessment of PsA activity correlated with the role limitations due to emotional problems. Bath ankylosing spondylitis functional index (BASFI) had the strongest correlation with the physical functioning concept of SF-36 in both diseases. Our findings provide important information to help selecting the variables with strongest impact on QOL, for better planning the management strategies and achieving better rehabilitation results. PMID- 22065070 TI - Is psychological distress intrinsic to fibromyalgia syndrome? Cross-sectional analysis in two clinical presentations. AB - Clinical presentation of fibromyalgia syndrome (FMS) is heterogeneous and often involves psychological comorbidities. Clinical subgrouping of FMS patients has been proposed as a strategy to improve patients' long-term outcomes by helping identify specific treatment needs. Using the 90 Symptom Checklist Revised (SCL-90 R), we have assessed emotional distress in two FMS patient subpopulations discriminated on the basis of their differences in scores on specific items of the Fibromyalgia Impact Questionnaire (FIQ). Subjects classed as type II exhibited high emotional distress on all ten dimensions studied, which included somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism, and additional items subscales, as well as on the global severity index (GSI), positive symptom total (PST), and positive symptom distress index (PDSI). T scores in these patients were above diagnostic cutoff level of 60 on somatization, obsessive-compulsive, and depression subscales. In contrast, the profile exhibited by type I subjects fell entirely within normal values for nonpsychiatric population. Emotional status was significantly inversely correlated with present clinical pain in type I-, but not in type II-fibromyalgia patients. Regression analysis revealed a model based on phobic anxiety, paranoid ideation, and depression subscales as best contributing to classification. The present data suggest that associated psychological distress and maladaptive emotional responses that are commonly attributed to the general FMS population may be largely a distinguishing feature of one subset of patients. PMID- 22065071 TI - Midterm clinico-radiologic findings of an open label observation study of add-on tacrolimus with biologics or non-biologic DMARDs. AB - Tacrolimus (TAC) suppresses immune-inflammation by an intermediary inhibition of calcineurin activation in the treatment of rheumatoid arthritis (RA). Various combination therapies for RA have been reported to be superior to monotherapies. The aim was therefore to study add-on TAC in a combination with biologics (BIO) and/or non-BIO disease-modifying anti-rheumatic drugs (DMARDs) in treatment resistant patients. In eight RA patients, TAC was added on to BIO (TAC/BIO group) and in forty-one to non-BIO DMARDs (TAC/non-BIO group). The mean C-reactive protein (CRP) decreased from 33 mg/l at the baseline to 16 mg/l at first year in the TAC/BIO group (P < 0.05), from 41 to 14 mg/l in the TAC/non-BIO group (P < 0.05); the mean DAS28-CRP (28 joint count) disease activity score decreased from 5.3 to 4.4 in the TAC/BIO group (P < 0.05) and from 5.0 to 3.9 in the TAC/non-BIO group (P < 0.05). The median of Delta modified total Sharp score decreased from 43 during the year preceding the baseline to 3 during the first year of the follow-up in the TAC/BIO group (P < 0.05) and from 22 to 0 during the second year in the TAC/non-BIO group (P < 0.05). Twenty-six adverse events occurred in this study in 26 patients (53% in all); however, the only severe adverse event was one case of an atypical mycobacterial disease (2%). The combination therapy of TAC with BIO or non-BIO DMARDs represents an effective and relatively safe mode of therapy in treatment-resistant RA. PMID- 22065072 TI - Perspectives on quality and content of information for juvenile idiopathic arthritis on Italian Web pages: a different way to meet the needs of families? PMID- 22065073 TI - Positive power Doppler signal in plantar fasciitis. AB - The plantar fascia is a multilayered band of fibrous tissue that support and maintain the longitudinal arch of the foot. We report a 34-old obese woman with heel pain for the past 3 years. On physical examination, she presented painful plantar fascia throughout extension of the foot. In addition, a soft painful, mobile nodule was also palpated in the medial aspect of her left heel. An US examination of her left foot showed an increased thickness of her plantar fascia with reduced echogenity, the presence of an effusion and a positive power Doppler signal. Positive US Doppler signal may be helpful in evaluating patients with plantar fasciitis and is suggestive of the presence of active microcirculation. PMID- 22065074 TI - Correlation of serum prolactin levels and disease activity in systematic lupus erythematosus. AB - To assess the frequency of hyperprolactinaemia and its possible clinical significance in patients with systemic lupus erythematosus (SLE). In this cross sectional study, we determined serum prolactin (PRL) levels in 60 SLE female patients (age range 15-60 years). Disease activity was defined according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Serum PRL concentrations were determined by immunoradiometric assay. Elevated serum concentrations of PRL (>20 ng/ml) were found in 5 of 60 (8.4%) patients. No direct correlation between PRL levels with disease activity of SLE was found (r = 0.062, P = 0.39). SLE was active in 23 patients (SLEDAI >= 6) and inactive in 37 (SLEDAI < 6). In those with active disease, median PRL levels were lower (11.0 ng/ml) than normoprolactinaemic group (12.1 ng/ml). There was no significant difference in serum PRL levels between active and non-active patients (P = 0.07). There was a significant difference in the frequency of several clinical manifestations and serological parameters between SLE patients with normal and high prolactin (renal involvement, haematological manifestation and anti-ds DNA). This study has shown that hyperprolactinaemia is prevalent in random SLE patients. The elevated PRL levels seem not to be associated with disease activity. The mechanism and pathoaetiological and clinical significance of hyperprolactinaemia in a small subset of SLE patients remain unclear and a longer follow-up is necessary. PMID- 22065075 TI - A case of leukoencephalopathy associated with adalimumab-treated rheumatoid arthritis and a review of literature. AB - Tumor necrosis factor-alpha (TNF-alpha) inhibitor is recently being widely used to treat autoimmune diseases, but some noticeable adverse events were reported and neurological events have especially been described. It is mandatory to compare these cases for finding the risk factors, the duration of the neurological events, their processes and their outcomes. We present here the case of leukoencephalopathy secondary to adalimumab, which is a tumor necrosis factor alpha (TNF-alpha) inhibitor. We also reviewed the other 14 published leukoencephalopathy cases associated with the use of TNF inhibitors. Eleven patients had underlying rheumatoid arthritis, and the others had psoriatic arthritis, ankylosing spondylitis and Still's disease. The median duration of treatment with anti-TNF-alpha before the presentation of neurological symptoms was 9.2 months (range: 1.5-24). The duration of using anti-TNF-alpha was not related with the outcome. Although cases of neurological adverse events associated with anti-TNF-alpha treatment are rare, it is very important to monitor the neurological signs and symptoms suggestive of a demyelinating disorder in RA patients who are receiving anti-TNF-alpha treatment and especially those patients who are older and who have a history of MS or demyelination. PMID- 22065076 TI - Novel photosensory two-component system (PixA-NixB-NixC) involved in the regulation of positive and negative phototaxis of cyanobacterium Synechocystis sp. PCC 6803. AB - Two wild-type substrains of a motile cyanobacterium Synechocystis sp. PCC 6803 show positive phototaxis toward a light source (PCC-P) and negative phototaxis away from light (PCC-N). In this study, we found that a novel two-component system of photoresponse is involved in the phototactic regulation. Inactivation of slr1212 (pixA), which encodes a photoreceptor histidine kinase, reverted the positive phototaxis of PCC-P to negative phototaxis, and inactivation of the downstream slr1213 (nixB) and slr1214 (nixC), which encode AraC-like transcription factor-type and PatA-type response regulators, respectively, reverted the negative phototaxis of PCC-N to positive phototaxis. Opposite effects of pixA and nixBC disruption implies an unexpected signal transduction pathway in the switching of positive and negative phototaxis. The blue/green-type cyanobacteriochrome GAF domain of PixA was expressed in Synechocystis and phycocyanobilin-producing Escherichia coli. The holoprotein covalently bound a chromophore phycoviolobilin and showed reversible photoconversion between the violet- (Pv, lambda(peak) = 396 nm) and green-absorbing (Pg, lambda(peak) = 533 nm) forms, although the protein from E. coli partially bound a precursor phycocyanobilin. These results were discussed with regard to an idea that PixA serves as a violet light receptor for switching of positive and negative phototaxis by transcriptional and functional regulation. PMID- 22065077 TI - Multiple myeloma mesenchymal stem cells: characterization, origin, and tumor promoting effects. AB - Hematologic malignancies rely heavily on support from host cells through a number of well-documented mechanisms. Host cells, specifically mesenchymal stem cells (MSC), support tumor cell growth, metastasis, survival, bone marrow colonization, and evasion of the immune system. In multiple myeloma, similar to solid tumors, supporting cells have typically been considered healthy host cells. However, recent evidence reveals that many MSCs derived from patients with multiple myeloma (MM-MSC) show significant defects compared with MSCs from nondiseased donors (ND-MSC). These abnormalities range from differences in gene and protein expression to allelic abnormalities and can initiate after less than 1 day of coculture with myeloma cells or persist for months, perhaps years, after removal from myeloma influence. Alterations in MM-MSC function contribute to disease progression and provide new therapeutic targets. However, before the scientific community can capitalize on the distinctions between MM-MSCs and ND-MSCs, a number of confusions must be clarified, as we have done in this review, including the origin(s) of MM-MSCs, identification and characterization of MM-MSCs, and downstream effects and feedback circuits that support cancer progression. Further advances require more genetic analysis of MM-MSCs and disease models that accurately represent MSC-MM cell interactions. PMID- 22065078 TI - BEAMing sheds light on drug resistance. AB - Targeted therapies against somatically altered genes are currently used for the treatment of many human cancers. The nascent technology known as BEAMing has the potential to increase the clinical utility of these agents because it allows for the detection of cancer mutations in peripheral blood, providing a rapid assessment of tumor mutation status. PMID- 22065079 TI - Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma. AB - Malignant mesothelioma is an aggressive malignancy related to asbestos and erionite exposure. AP-1 transcriptional activity and the NF-kappaB signaling pathway have been linked to mesothelial cell transformation and tumor progression. HGF and c-Met are highly expressed in mesotheliomas. Phosphoinositide 3-kinase, AKT, and the downstream mTOR are involved in cell growth and survival, and they are often found to be activated in mesothelioma. p16(INK4a) and p14(ARF) are frequently inactivated in human mesothelioma, and ~50% of mesotheliomas contain the NF2 mutation. Molecular therapies aimed at interfering with these pathways have not improved the dismal prognosis of mesothelioma, except possibly for a small subset of patients who benefit from certain therapies. Recent studies have shown the importance of asbestos-induced inflammation in the initiation and growth of mesothelioma, and HMGB1 and Nalp3 inflammasome have been identified as key initiators of this process. Asbestos induces cell necrosis, causing the release of HMGB1, which in turn may activate Nalp3 inflammasome, a process that is enhanced by asbestos-induced production of reactive oxygen species. HMGB1 and Nalp3 induce proinflammatory responses and lead to interleukin-1beta and TNF-alpha secretion and NF-kappaB activity, thereby promoting cell survival and tumor growth. Novel strategies that interfere with asbestos- and erionite-mediated inflammation might prevent or delay the onset of mesothelioma in high-risk cohorts, including genetically predisposed individuals, and/or inhibit tumor growth. The very recent discovery that germline BAP1 mutations cause a new cancer syndrome characterized by mesothelioma, uveal melanoma, and melanocytic tumors provides researchers with a novel target for prevention and early detection. PMID- 22065080 TI - Antitumor activity of NVP-BKM120--a selective pan class I PI3 kinase inhibitor showed differential forms of cell death based on p53 status of glioma cells. AB - PURPOSE: The aim of this study was to show preclinical efficacy and clinical development potential of NVP-BKM120, a selective pan class I phosphatidylinositol 3 kinase (PI3K) inhibitor in human glioblastoma (GBM) cells in vitro and in vivo. EXPERIMENTAL DESIGN: The effect of NVP-BKM120 on cellular growth was assessed by CellTiter-Blue assay. Flow cytometric analyses were carried out to measure the cell-cycle, apoptosis, and mitotic index. Mitotic catastrophe was detected by immunofluorescence. The efficacy of NVP-BKM120 was tested using intracranial U87 glioma model. RESULTS: We tested the biologic effects of a selective PI3K inhibitor NVP-BKM120 in a set of glioma cell lines. NVP-BKM120 treatment for 72 hours resulted in a dose-dependent growth inhibition and effectively blocked the PI3K/Akt signaling cascade. Although we found no obvious relationship between the cell line's sensitivity to NVP-BKM120 and the phosphatase and tensin homolog (PTEN) and epidermal growth factor receptor (EGFR) statuses, we did observe a differential sensitivity pattern with respect to p53 status, with glioma cells containing wild-type p53 more sensitive than cells with mutated or deleted p53. NVP-BKM120 showed differential forms of cell death on the basis of p53 status of the cells with p53 wild-type cells undergoing apoptotic cell death and p53 mutant/deleted cells having a mitotic catastrophe cell death. NVP-BKM120 mediates mitotic catastrophe mainly through Aurora B kinase. Knockdown of p53 in p53 wild type U87 glioma cells displayed microtubule misalignment, multiple centrosomes, and mitotic catastrophe cell death. Parallel to the assessment of the compound in in vitro settings, in vivo efficacy studies using an intracranial U87 tumor model showed an increased median survival from 26 days (control cohort) to 38 and 48 days (treated cohorts). CONCLUSION: Our present findings establish that NVP BKM120 inhibits the PI3K signaling pathways, leading to different forms of cell death on the basis of p53 statuses. Further studies are warranted to determine if NVP-BKM120 has potential as a glioma treatment. PMID- 22065081 TI - Modulation of the tumor microvasculature by phosphoinositide-3 kinase inhibition increases doxorubicin delivery in vivo. AB - PURPOSE: Because effective drug delivery is often limited by inadequate vasculature within the tumor, the ability to modulate the tumor microenvironment is one strategy that may achieve better drug distribution. We have previously shown that treatment of mice bearing tumors with phosphoinositide-3 kinase (PI3K) inhibitors alters vascular structure in a manner analogous to vascular normalization and results in increased perfusion of the tumor. On the basis of that result, we asked whether inhibition of PI3K would improve chemotherapy delivery. EXPERIMENTAL DESIGN: Mice with xenografts using the cell line SQ20B bearing a hypoxia marker or MMTV-neu transgenic mice with spontaneous breast tumors were treated with the class I PI3K inhibitor GDC-0941. The tumor vasculature was evaluated by Doppler ultrasound, and histology. The delivery of doxorubicin was assessed using whole animal fluorescence, distribution on histologic sections, high-performance liquid chromatography on tumor lysates, and tumor growth delay. RESULTS: Treatment with GDC-0941 led to approximately three fold increases in perfusion, substantially reduced hypoxia and vascular normalization by histology. Significantly increased amounts of doxorubicin were delivered to the tumors correlating with synergistic tumor growth delay. The GDC 0941 itself had no effect on tumor growth. CONCLUSION: Inhibition of PI3K led to vascular normalization and improved delivery of a chemotherapeutic agent. This study highlights the importance of the microvascular effects of some novel oncogenic signaling inhibitors and the need to take those changes into account in the design of clinical trials many of which use combinations of chemotherapeutic agents. PMID- 22065082 TI - Targeting tumor-associated endothelial cells: anti-VEGFR2 immunoliposomes mediate tumor vessel disruption and inhibit tumor growth. AB - PURPOSE: Angiogenesis is a key process in tumor progression. By binding VEGF, VEGF receptor-2 (VEGFR2) is a main signaling transducer in tumor-associated angiogenesis. Accordingly, therapeutic approaches against the VEGF/VEGFR2 signaling axis have been designed. However, an efficient and specific chemotherapeutic targeting of tumor-associated endothelial cells has not yet been achieved. EXPERIMENTAL DESIGN: We have employed anti-VEGFR2 antibodies covalently linked to pegylated liposomal doxorubicin (PLD) to specifically ablate tumor associated endothelial cells in the Rip1Tag2 mouse model of insulinoma, in the MMTV-PyMT mouse model of breast cancer, and in the HT-29 human colon cancer xenograft transplantation model. RESULTS: In each model, anti-VEGFR2-targeted immunoliposomes (ILs) loaded with doxorubicin (anti-VEGFR2-ILs-dox) were superior in therapeutic efficacy to empty liposomes, empty anti-VEGFR2-ILs, antibodies alone, and PLD. Efficacy was similar to that of the oral VEGFR1, -2, and -3 inhibitor PTK787. Detailed histopathologic and molecular analysis revealed a strong antiangiogenic effect of anti-VEGFR2-ILs-dox, and the observed antiangiogenic therapy was significantly more efficient in reducing tumor burden in well-vascularized transgenic mouse models as compared with the less vascularized xenograft model. CONCLUSIONS: Anti-VEGFR2 ILs provide a highly efficient approach to selectively deplete VEGFR2-expressing tumor vasculature. They offer a novel and promising anticancer strategy. PMID- 22065083 TI - Antitumor activity of sustained N-myc reduction in rhabdomyosarcomas and transcriptional block by antigene therapy. AB - PURPOSE: Rhabdomyosarcomas are a major cause of cancer death in children, described with MYCN amplification and, in the alveolar subtype, transcription driven by the PAX3-FOXO1 fusion protein. Our aim was to determine the prevalence of N-Myc protein expression and the potential therapeutic effects of reducing expression in rhabdomyosarcomas, including use of an antigene strategy that inhibits transcription. EXPERIMENTAL DESIGN: Protein expression was assessed by immunohistochemistry. MYCN expression was reduced in representative cell lines by RNA interference and an antigene peptide nucleic acid (PNA) oligonucleotide conjugated to a nuclear localization signal peptide. Associated gene expression changes, cell viability, and apoptosis were analyzed in vitro. As a paradigm for antigene therapy, the effects of systemic treatment of mice with rhabdomyosarcoma cell line xenografts were determined. RESULTS: High N-Myc levels were significantly associated with genomic amplification, presence of the PAX3/7-FOXO1 fusion genes, and proliferative capacity. Sustained reduction of N-Myc levels in all rhabdomyosarcoma cell lines that express the protein decreased cell proliferation and increased apoptosis. Positive feedback was shown to regulate PAX3-FOXO1 and N-Myc levels in the alveolar subtype that critically decrease PAX3 FOXO1 levels on reducing N-Myc. Pharmacologic systemic administration of the antigene PNA can eliminate alveolar rhabdomyosarcoma xenografts in mice, without relapse or toxicity. CONCLUSION: N-Myc, with its restricted expression in non fetal tissues, is a therapeutic target to treat rhabdomyosarcomas, and blocking gene transcription using antigene oligonucleotide strategies has therapeutic potential in the treatment of cancer and other diseases that has not been previously realized in vivo. PMID- 22065084 TI - Concurrent temozolomide and dose-escalated intensity-modulated radiation therapy in newly diagnosed glioblastoma. AB - PURPOSE: To determine the maximum-tolerated dose (MTD) of radiation (RT) with concurrent temozolomide in patients with newly diagnosed glioblastoma (GBM), to estimate their progression-free (PFS) and overall survival (OS), and to assess the role of (11)C methionine PET (MET-PET) imaging in predicting recurrence. EXPERIMENTAL DESIGN: Intensity-modulated RT (IMRT) doses of 66 to 81 Gy, assigned to patients by the time-to-event continual reassessment method, were delivered over 6 weeks with concurrent daily temozolomide (75 mg/m(2)) followed by adjuvant cyclic temozolomide (200 mg/m(2) d1-5 q28d *6 cycles). Treatment was based on gadolinium-enhanced MRI. Pretreatment MET-PET scans were obtained for correlation with eventual sites of failure. RESULTS: A total of 38 patients were analyzed with a median follow-up of 54 months for patients who remain alive. Late CNS grade >=III toxicity was observed at 78 (2 of 7 patients) and 81 Gy (1 of 9 patients). None of 22 patients receiving 75 or less Gy developed RT necrosis. Median OS and PFS were 20.1 (14.0-32.5) and 9.0 (6.0-11.7) months, respectively. Twenty-two of 32 patients with pretreatment MET-PET uptake showed uptake beyond the contrast-enhanced MRI. Patients whose treatment did not include the region of increased MET-PET uptake showed an increased risk of noncentral failure (P < 0.001). CONCLUSIONS: Patients with GBM can safely receive standard temozolomide with 75 Gy in 30 fractions, delivered using IMRT. The median OS of 20.1 months is promising. Furthermore, MET-PET appears to predict regions of high risk of recurrence not defined by MRI, suggesting that further improvements may be possible by targeting metabolically active regions. PMID- 22065085 TI - A global view of the OCA2-HERC2 region and pigmentation. AB - Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160-170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535-542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Long-range haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele. PMID- 22065086 TI - A novel locus for autosomal dominant congenital motor nystagmus mapped to 1q31 q32.2 between D1S2816 and D1S2692. AB - Congenital motor nystagmus (CMN) is characterized by bilateral involuntary ocular oscillation without any other underlying ocular or systemic diseases. An autosomal dominant CMN was identified in a large Chinese family where all patients had nystagmus since infancy. The nystagmus in the family is independent of any known ocular or systemic diseases. After exclusion of known CMN loci, a genome-wide scan was performed by genotyping microsatellite markers at about 10 cM intervals, together with two-point linkage analysis. Exome sequencing was used to screen coding exons of well-annotated genes. Sanger-dideoxy sequencing was used to verify candidate variations inside the linkage interval. Congenital motor nystagmus in this family shows linkage to markers in a 11.39 Mb (12.1 cM) region on chromosome 1q31-q32.2 between D1S2816 and D1S2692. All nine markers in the linkage interval gave positive lod scores, with D1S2655 and D1S2636 yielding lod scores of 5.16 and 5.18, respectively, at theta = 0. No causative mutation in the linkage interval was identified by exome sequencing of gDNA from four patients. A linkage study of additional families and further analysis of candidate genes may ultimately lead to identification of the gene responsible for dominantly inherited CMN. PMID- 22065087 TI - Audit of acute Charcot's disease in the UK: the CDUK study. AB - AIMS/HYPOTHESIS: We studied factors associated with the development and resolution of acute Charcot foot using a web-based observational study. METHODS: Clinicians managing cases of acute Charcot foot in the UK and Ireland between June 2005 and February 2007 were invited to register anonymised details on a secure website. RESULTS: A total of 288 cases (age 57.0 +/- 11.3 years [mean +/- SD]; 71.2% male) were registered from 76 centres. Of these, 36% of patients recalled an episode of relevant trauma in the preceding 6 months, while 12% had had surgery to the affected foot. In 101 (35%) cases, ulceration was present at registration and 20% of these had osteomyelitis. Non-removable off-loading devices were used at presentation in 35.4% of cases, with removable off-loading used in 50%. Data on resolution were available for 219 patients. The median time to resolution was 9 months in patients whose initial management included the use of non-removable off-loading, compared with 12 months in the remainder (p = 0.001). Bisphosphonates were administered intravenously in 25.4% and orally in 19.4% of cases. The median time to resolution in patients who received bisphosphonates was 12 months and was longer than in those who did not (10 months, p = 0.005). CONCLUSIONS/INTERPRETATION: The median time to resolution was longer than in earlier series. Although limited by being observational and non randomised, these data suggest that the use of non-removable off-loading at presentation may shorten the time to resolution. They provide no evidence to indicate that the use of bisphosphonates is beneficial. PMID- 22065088 TI - Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. AB - AIMS/HYPOTHESIS: Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. METHODS: Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, beta-hydroxybutyrate, ketones, insulin and glucose were performed in baseline and 6 month plasma samples from 500 participants who had lost >=4 kg during Phase I of the Weight Loss Maintenance (WLM) trial. Homeostatic model assessment of insulin resistance (HOMA-IR) and change in HOMA-IR with weight loss (?HOMA-IR) were calculated. Principal components analysis (PCA) and mixed models adjusted for race, sex, baseline weight, and amount of weight loss were used; findings were validated in an independent cohort of patients (n = 22). RESULTS: Mean weight loss was 8.67 +/- 4.28 kg; mean ?HOMA-IR was -0.80 +/- 1.73, range 28.9 to 4.82). Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR (r = 0.50, p < 0.0001) and independently associated with ?HOMA-IR (p < 0.0001). ?HOMA-IR increased in a linear fashion with increasing baseline factor 3 quartiles. Amount of weight loss was only modestly correlated with ?HOMA-IR (r = 0.24). These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting ?HOMA-IR (p = 0.007). CONCLUSIONS/INTERPRETATION: A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity. PMID- 22065089 TI - Evaluation of teicoplanin dosing designs to achieve a new target trough concentration. AB - Minimum inhibitory concentration (MIC) creep in vancomycin has prompted guidelines that recommend a target trough concentration (C (min)) of 15-20 mg/L, and it is also considered necessary to set a C (min) of >15 mg/L for teicoplanin (TEIC), especially in patients with complicated methicillin-resistant Staphylococcus aureus (MRSA) infections. The aim of this study was to investigate the appropriate TEIC regimen for reaching the revised target C (min) (15-30 mg/L) in patients with normal renal function and those with renal dysfunction. We analyzed patients with MRSA infections who were treated with TEIC between July 2006 and December 2009. Two-day loading regimen was studied in patients with non renal-dysfunction (group 1). The 1-day loading regimen was studied in patients with non-renal-dysfunction (group 2, control) and in patients with renal dysfunction (group 3). The 178 patients in the study consisted of 76, 28, and 74 patients in groups 1, 2, and 3, respectively. C (min) on day 4 was 14.6 +/- 5.6, 11.9 +/- 4.1, and 13.5 +/- 4.2 mg/L, and the proportion of patients achieving the revised target range was 34.2%, 17.9%, and 20.3%, respectively. Only one patient in group 1 revealed C (min) of >30 mg/L. Treatment success rates, nephrotoxicity, and hepatotoxicity were similar among the three groups. It was difficult to achieve the revised target C (min) with the 2-day loading regimen in patients without renal dysfunction and with the standard TEIC regimen, even in patients with renal dysfunction. Further investigation of an even higher TEIC dosing regimen is considered necessary. PMID- 22065090 TI - Necrotizing fasciitis following psoas muscle abscess caused by hypermucoviscous Klebsiella pneumoniae. AB - A 59-year-old Japanese diabetic woman was admitted to a small private hospital with general malaise, fever, and a 1-month history of low back pain. A computed tomography scan of the abdomen revealed left abdominal necrotizing fasciitis with suspected left psoas muscle abscess. She was transferred to Gunma University Hospital, received antibiotic therapy, and underwent debridement of the infected subcutaneous tissue, fascia, and necrotic left psoas muscle. She was transferred to the intensive care unit to receive mechanical ventilation and inotropic support. Blood culture showed growth of Klebsiella pneumoniae, from which hypermucoviscosity was detected by the string test. She was extubated on day 5 of hospitalization and transferred to a general ward on day 14. Free skin grafting was performed on day 76, and she was discharged on day 134 without any complications. PMID- 22065091 TI - Prevalence and clinical usefulness of antiphospholipid and anticofactor antibodies in different Spanish preeclampsia subsets. AB - OBJECTIVE: To study the prevalence and clinical usefulness of antiphospholipid antibodies in different preeclampsia subsets. DESIGN: Observational cross sectional study. SETTING: Tertiary teaching hospital. PATIENTS: Ninety-nine women with preeclampsia versus 83 healthy pregnant women as controls. INTERVENTIONS: We analysed anticardiolipin IgG/IgM, anti-beta(2)glycoprotein IgG/IgM, antiphosphatidylserine IgG/IgM, antiAnnexin-A5 IgG/IgM, and lupus anticoagulant. MAIN OUTCOME MEASURE: Comparison of antiphospholipid antibody positivity between groups. RESULTS: Antiphospholipid antibody prevalence was 14.14% in the study group vs. 7.23% in controls. Excluding antiAnnexin-A5-positive women, overall antiphospholipid prevalence was 13.19% vs. 3.61% (p = 0.034). Only IgM anticardiolipin positivity showed significant differences between preeclampsia group and controls (8.1% vs. 1.20%, p = 0.041). Comparing a severe preeclampsia subset vs. controls, we obtained these significant results: for two or more positive antiphospholipid tests: 9.09% vs. 1.20 (p = 0.037); IgM-anticardiolipin 10.91% vs. 1.20% (p = 0.016); IgG/IgM-anti-beta(2)glycoprotein-I 10.91% vs. 1.90% (p = 0.016), IgM-anti-beta(2)glycoprotein-I 9.09% vs.1.20 (p = 0.037). When comparing early-onset preeclampsia vs. controls we found IgM-anticardiolipin 11.11% vs. 1.20% (p = 0.029). CONCLUSIONS: Prevalence of antiphospholipid antibodies in preeclampsia patients is twice that in healthy pregnant women. Multipositive aPL test, IgM-anticardiolipin and IgM-anti-beta(2)glycoprotein-I isotypes showed an association with severe and early-onset preeclampsia. Larger studies are needed to establish the usefulness of antiphospholipid tests as risk markers for severe and early onset preeclampsia. PMID- 22065092 TI - Environment and lupus-related diseases. AB - Clinical manifestations of lupus are encountered in a variety of disease entities, including isolated cutaneous lupus, undifferentiated connective tissue disease, mixed connective tissue disease, drug-induced lupus, overlap syndrome, and systemic lupus erythematosus (SLE). While each entity has been recognized as a specific disease with its own diverse clinical and serological pattern, one could argue that many findings are common. Could it be that all of these entities actually represent a spectrum of one disease? Could it be that rather than the genetic predisposition and hence controlled factors that govern this spectrum of diseases, that environmental factors associated with SLE could also play a role in the different entities of this spectrum? The traditional environmental triggers in SLE include sunlight and ultraviolet (UV) light, infections, smoking, and medications including biologics such as tumor necrosis factor alpha (TNF-a) blockers. In this review, we update and further substantiate these traditional factors in the various lupus-related syndromes. We will also discuss the association with vaccine exposure, industrial estrogens, and other factors. PMID- 22065093 TI - Vitamin D status in systemic lupus erythematosus patients and its association with selected clinical and laboratory parameters. AB - OBJECTIVES: To identify relationships between vitamin D serum levels and the presence of autoantibodies directed against vitamin D and levels of interleukin(IL)-17 and IL-23 in patients with systemic lupus erythematosus (SLE). METHODS: The study included 49 patients with SLE. Serum concentrations of 25(OH)D(3) were measured with electrochemiluminescence immunoassay (ECLIA). Enzyme-linked immunosorbent assays (ELISA) were used to determine antibodies directed against 1,25(OH)(2)D(3) and levels of IL-17 and IL-23 in serum of SLE patients. In evaluation of vitamin D status, the control group consisted of 49 age and gender matched healthy individuals, whereas in assessment of anti-vitamin D antibodies the control group comprised 30 sera from blood donors. RESULTS: Serum concentration of 25(OH)D(3) in SLE patients during the warm season was 18.47 +/- 9.14 ng/ml, which was significantly decreased as compared with that of the control group - 31.27 +/- 12.65 ng/ml (p = 0.0005). During the cold season a trend toward lower concentration of 25(OH)D(3) in SLE patients was revealed; however, it did not reach statistical significance (11.71 +/- 7.21 ng/ml vs. 16.01 +/- 8.46 ng/ml; p = 0.054). Results within the recommended range for vitamin D (30-80 ng/ml; 70-200 nmol/l) were observed only in three patients. The 25(OH)D(3) concentration was decreased in SLE patients with renal disease or leucopenia as compared with the levels in patients who did not have either problem (p = 0.006 and p = 0.047, respectively). The cold season was found to be a risk factor for vitamin D deficiency (<20 ng/ml) (odds ratio = 9.25; p = 0.005). Autoantibodies directed against 1,25(OH)(2)D(3) were detected in three SLE patients. No significant difference in 25(OH)D(3) serum concentrations was found between SLE patients with and without these autoantibodies. No link was shown between the existence of autoantibodies against 1,25(OH)(2)D(3) and clinical or laboratory findings, including IL-17 and IL-23 levels. However, serum concentrations of IL-23 were lower in patients with vitamin D deficiency (p = 0.037). CONCLUSIONS: SLE patients, especially those with leucopenia or renal involvement, are at high risk of vitamin D deficiency and require vitamin D supplementation. Some SLE patient sera contained 1,25(OH)(2)D(3) antibodies, but these antibodies do not appear to affect vitamin D levels. PMID- 22065094 TI - Cutaneous phaeohyphomycosis caused by Exophiala spinifera in a patient with systemic lupus erythematosus. AB - Exophiala spinifera can induce both phaeohyphomycosis and chromomycosis. To date there have been 18 human infections caused by E. spinifera in the English literature. A case of E. spinifera-induced phaeohyphomycosis in a patient with systemic lupus erythematosus (SLE) is described. Direct microscopic examination of the pus showed branched, septate and chained hyphae and spores. A dark green velvety colony grew on Sabouraud dextrose agar. Slide culture showed branched, septate hyphae and spine-like annellated conidiophores. Histopathological biopsy revealed yellowish brown hyphae and spores. The isolate was identified as E. spinifera by DNA sequence analysis. The strain was unable to liquefy gelatin, grew at 25 degrees C to 39 degrees C, and was sensitive to itraconazole, amphotericin B, and terbinafine. To our knowledge, this is the first case of cutaneous phaeohyphomycosis caused by E. spinifera in SLE patients. PMID- 22065095 TI - TLR7/8/9 polymorphisms and their associations in systemic lupus erythematosus patients from southern Brazil. AB - Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and can affect several organs and systems. It is characterized by high production of autoantibodies against nuclear compounds. TLR7/8/9 are responsible for nucleic acid recognition and they trigger proinflammatory responses through activation of NK-kappaB and Type I IFN production, making a bridge between the innate and the adaptative immune systems. We analyzed the frequency of TLR7 rs179008, TLR8 rs3764880, TLR9 rs5743836 and rs352140 in 370 patients with SLE and 415 healthy controls from southern Brazil. All analyses were conducted with regard to gender and ethnicity. Genotypic and allelic frequencies were different for TLR7 rs179008 (0.253 vs. 0.163, p = 0.020 and p = 0.003, OR for T allele: 1.74 CI 95% 1.12 2.70) and TLR9 rs5743836 (0.174 vs. 0.112, p = 0.045 and p = 0.017, OR for C allele: 1.59, CI 95% 0.99-2.57) between European-derived female groups. A higher frequency was observed for the presence of Anti-SSa/Ro for TRL9 rs5743836 C allele carriers (0.228 vs 0.126, Bonferroni corrected p = 0.06). No statistical differences were found for TLR9 haplotypic analyses. We suggest that TLR7 rs179008 and TLR9 rs5743836 can be considered SLE susceptibility factors for women of European descent in our population. PMID- 22065096 TI - 17beta-Estradiol (E-2) administration to male (NZB * SWR)F1 mice results in increased Id(LN)F1-reactive memory T-lymphocytes and accelerated glomerulonephritis. AB - While it has been shown that estradiol treatment accelerates the onset of lupus nephritis with autoantibody production and kidney damage in both male and female lupus-prone mice, the specific mechanism(s) involved are unknown. Our previous work has shown that alterations in Id(LN)F(1)-reactive T cells and Id(LN)F(1)+ antibodies correlated closely with the onset of autoimmune nephritis in female F(1) progeny of SWR and NZB (SNF(1)) mice, supporting a critical role for the Id(LN)F(1) idiotype in the development of disease. Since male SNF(1) mice normally do not develop nephritis, we tested whether administration of 17beta estradiol (E-2) to male SNF(1) mice would increase Id(LN)F(1) IgG levels and autoreactive T cells, and further, induce nephritis. We found that E-2-treated male SNF(1) mice developed nephritis with the same time course and mean survival as normal female SNF(1) mice. Moreover, it appeared that the mechanism involved increased serum Id(LN)F(1)(+)IgG and its deposition in kidney glomeruli, preceded by a striking twofold increase in T-lymphocytes expressing the memory phenotype (CD44(+)CD45RB(lo)) predominantly in the Id(LN)F(1)-reactive T-cell population. In addition, we noted that cells with this phenotype were increased in the nephritic kidneys of treated mice, suggesting a direct involvement of those cells in the renal pathology. E-2 treatment also induced increased numbers of pathogenic Id(LN)F(1)+ antibody-producing B cells and elevated presentation of pathogenic Id(LN)F(1)+ peptide. Taken together, these results suggest a mechanism of E-2-induced acceleration of autoimmune disease in lupus-prone mice may involve expansion of autoreactive idiotypic T and B-cell populations. PMID- 22065097 TI - Cardiovascular event in systemic lupus erythematosus in northern Sweden: incidence and predictors in a 7-year follow-up study. AB - INTRODUCTION: An increased rate of cardiovascular disease (CVD) has been suggested in patients with systemic lupus erythematosus (SLE). The risk for myocardial infarction (MI), coronary artery disease and stroke has been reported as particularly prevalent in younger females compared with the reference population. This study was performed to analyse the standard incidence ratio (SIR) of and predictors for cardiovascular events (CVEs) in patients with SLE from northern Sweden, with a fairly homogenous population. METHODS: In 2000 all prevalent patients with SLE (>=4 American College of Rheumatology [ACR] criteria; n = 277) from the four northern-most counties of Sweden were assessed with clinical and laboratory analyses. Seven years follow-up data concerning MI and stroke were extracted from the national registers of hospitalization and death in Sweden. The incidence ratio among the patients was compared with that for the general population from the same catchment area using data from the same register and Statistics Sweden. To identify time to event and CVE predictors, two matched controls for each patient were used and disease related variables as CVD predictors. RESULTS: The SIR for a CVE was 1.27 (95% CI 0.82-1.87) and for females separately aged 40-49 years was 8.00 (95% CI 1.65-23.38). The overall SIR for MI was 2.31 (95% CI 1.34-3.7), for females overall was 1.75 (95% CI 0.84 3.22) and for females aged between 40 and 49 years was 8.7 (95% CI 1.1-31.4). The time to an event was significantly shorter among SLE patients (p < 0.001) and was predicted by hypertension adjusted for smoking and disease. High SLEDAI and anti cardiolipin IgG antibodies predicted an event in Cox proportional hazards regression models adjusted for age and previous MI. Diabetes, smoking ever and sex did not affect the prediction models. CONCLUSION: The risk of a CVE, or MI, was eight- or nine-fold greater among middle-aged female SLE patients. Time to event was significantly shorter and CVE was associated with SLE-related factors including hypertension and age. PMID- 22065098 TI - Disparate effects of depletion of CD1d-reactive T cells during early versus late stages of disease in a genetically susceptible model of lupus. AB - Some T cells react with lipid antigens bound to antigen-presenting molecule CD1d. Numbers and functions of a subset of such lipid-reactive T cells are reduced in patients with systemic lupus erythematosus (SLE) and their relatives, as well as in genetically susceptible and chemically induced animal models of lupus-like disease. We have reported that the germline deletion of CD1d exacerbates lupus, suggesting a protective role of these cells in the development of lupus. The use of a knockout mouse model in this study, however, did not allow examination of the role of these cells at different stages of disease. Here, we describe an approach to deplete CD1d-dependent T cells, which allowed us to investigate the role of these cells at different stages of disease in genetically lupus-prone NZB/NZW F1 (BWF1) mice. Repeated intravenous injections of large numbers of CD1d transfected cells resulted in ~50-75% reduction in these cells, as defined by the expression of CD4, NK1.1 and CD122, and lack of expression of CD62 ligand. TCR gammadelta (+)NK1.1(+) cells were also reduced in the recipients of CD1d transfected cells as compared with control recipients. Such depletion of CD1d reactive T cells in preclinical BWF1 mice resulted in disease acceleration with a significant increase in proteinuria and mortality. In older BWF1 mice having advanced nephritis, however, such depletion of CD1d-reactive T cells resulted in some disease improvement. Taken together, these data as well as our published studies suggest that CD1d-reactive T cells protect against the development of lupus in animal models. However, these cells appear to be unable to suppress established lupus nephritis in these animals, and might even play a disease aggravating role in late stages of disease. PMID- 22065100 TI - The malignant neuroleptic syndrome (a review with report of three cases). PMID- 22065101 TI - Aqua-(dicyanamido-kappaN)(2,9-dimethyl-1,10-phenanthroline-kappaN,N')(nitrato kappaO,O')cobalt(II)-2,9-dimethyl-1,10-phenanthroline-water (2/1/2). AB - In the title compound, 2[Co(C(2)N(3))(NO(3))(C(14)H(12)N(2))(H(2)O)].C(14)H(12)N(2).2H(2)O, the Co(II) ion is coordinated by a bidentate 2,9-dimethyl-1,10-phenanthroline (dmphen) ligand, a bidentate nitrate anion, a water mol-ecule and a monodentate dicyan amide group in a distorted octa-hedral geometry. One uncoordinated dmphen mol ecule is situated on a crystallographic twofold axis and the asymmetric unit is completed by one water mol-ecule. In the crystal, mol-ecules form a one dimensional framework in the [001] direction through O-H?N and O-H?O hydrogen bonds. The crystal packing is further stabilized by pi-pi stacking inter-actions between the dmphen rings of neighboring mol-ecules, with a centroid-centroid separation of 3.5641 (8) A and a partially overlapped arrangement of parallel dmphen rings with a distance of 3.407 (2) A. PMID- 22065099 TI - Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies. AB - Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID- 22065102 TI - Aptamer-based modulation of blood coagulation. AB - Nucleic acid based aptamers are single-stranded oligonucleotide ligands isolated from random libraries by an in-vitro selection procedure. Through the formation of unique three-dimensional structures, aptamers are able to selectively interact with a variety of target molecules and are therefore also promising candidates for the development of anticoagulant drugs. While thrombin represents the most prominent enzymatic target in this field, also aptamers directed against other coagulation proteins and proteases have been identified with some currently being tested in clinical trials. In this review, we summarize recent developments in the design and evaluation of aptamers for anticoagulant therapy and research. PMID- 22065104 TI - Hydronephrosis caused by a relapse of granulomatosis with polyangiitis (Wegener's). AB - We describe a case of relapsed granulomatosis with polyangiitis (Wegener's) (GPA) that presented with abdominal pain. (18)F-fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET)/computed tomography (CT) clearly depicted an inflammation of the left peri-iliac arterial soft tissue, which was thought to be the cause of the ureteral obstruction and hydronephrosis. Our case shows that peri-iliac arterial inflammation occurs in GPA and causes hydronephrosis. In addition, FDG-PET/CT is a useful tool for management of this systemic inflammatory disease. PMID- 22065105 TI - Transcutaneous interferential electrical stimulation for management of neurogenic bowel dysfunction in children with myelomeningocele. AB - PURPOSE: We describe the efficacy of transcutaneous interferential (IF) electrical stimulation on constipation symptoms in children with myelomeningocele (MMC). METHODS: MMC children (30, comprising of 17 girls and 13 boys), mean age 6.7 +/- 2.9, with moderate to severe intractable constipation were enrolled in this study. They were divided into treatment (IF stimulation, 15 children) and control (sham stimulation, 15 children) groups. All children underwent anorectal manometry before and 6 months after IF therapy considering the rectoanal inhibitory reflex and sphincter pressure. Parents were instructed to complete a bowel habit diary by providing data on the number of defecations per week, form of stool and episodes of pain during defecation. According to parents' report a total neurogenic bowel dysfunction score questionnaire was filled before and 6 months after treatment. A 15-course abdominal area IF electrical stimulation was performed for 20 min and three times per week, with low-frequency current in a duration of 250 MUs every 6 s. Children were followed up for a minimum period of 6 months. RESULTS: In the treatment group, sphincter pressure and rectoanal inhibitory reflex significantly improved compared with sham stimulation and pretreatment measures (P < .05). In 73% of patients, the characteristics of constipation decreased immediately after IF therapy, while in 53% patients, they persisted for 6 months. Frequency of defecation increased statistically significant from 2.5 +/- 1.1 per week before treatment to 4.7 +/- 2.3 per week after treatment (P < .001). CONCLUSIONS: This pilot study showed that IF therapy is safe, noninvasive, and effective modality to improve constipation symptoms and anorectal manometry parameters in children with history of myelomeningocele. PMID- 22065106 TI - Quality of life after laparoscopic resection rectopexy. AB - PURPOSE: This study evaluated continence, constipation, and quality of life (QoL) after laparoscopic resection rectopexy (LRR) for full-thickness rectal prolapse. Results were compared with existing data after perineal rectosigmoidectomy (PRS). METHODS: From May 2003 to February 2008, consecutive patients suffering from full thickness rectal prolapse undergoing LRR were retrospectively studied. A standardized questionnaire including the Cleveland Clinic Constipation and Incontinence Scores (CCCS and CCIS) as well as general and constipation-related QoL scores (EQ-5D and PAC-QOL) was administered. Results were compared with those after PRS. For statistic analysis, the Wilcoxon test (EQ-5D and EQ-VAS) and two sample Student's t test (CCCS, CCIS, and PAC-QOL) were used for LRR, for the comparison of both procedures Mann-Whitney test (EQ-5D) and two-sample Student's t test (EQ-VAS, CCCS, CCIS, and PAC-QOL). RESULTS: Eighteen patients, 15 female, aged 58.1 (+/-20.2) years underwent LRR. Eleven patients completed follow-up. Postoperatively, neither functional outcome nor QoL improved. Two recurrences occurred, morbidity was n = 2, and mortality n = 1. In comparison, patients after PRS benefit from improved constipation, general QoL measures, status of health, and all dimensions of constipation-related QoL. CONCLUSIONS: Patients after LRR do not benefit from improved general nor constipation-related QoL nor improved functional results compared to PRS. PMID- 22065107 TI - Impact of fat obesity on laparoscopic total mesorectal excision: more reliable indicator than body mass index. AB - BACKGROUND: The aim of this study was to evaluate the impact of visceral fat obesity (VFO) on early surgical and oncologic outcomes of laparoscopic total mesorectal excision (LTME) for rectal cancer. PATIENTS AND METHODS: Between June 2003 and June 2009, a total of 142 patients who had undergone LTME were included. Patients were divided into the obese group (OG) and the non-obese group (NOG) according to BMI and visceral fat area (VFA). Obesity was defined by BMI >=25 kg/m2 or VFA >=130 cm2. RESULTS: There were 37 (26.0%) and 29 (20.4%) obese patients according to BMI and VFA, respectively. The OG, defined by both VFA and BMI, had a significantly longer operative time. The VFO group experienced more frequent conversion to laparotomy (17.2% vs. 5.0%; P = 0.047) and significantly higher blood loss during surgery (205.8 +/- 257.0 mL vs. 102.5 +/- 219.9 mL; P = 0.031), whereas there was no significant difference when defined by BMI. Time to first flatus was significantly longer in the VFO group compared with the NOG (mean 3.5 days vs. 2.7 days; P = 0.046), whereas it was not significantly different when classified by BMI. Regarding oncologic parameters, the VFO group had a significantly higher number of patients from whom less than 12 total lymph nodes were retrieved (65.5% vs. 34.5%; P = 0.002); however, there was no difference between the two groups defined by BMI. CONCLUSION: VFO is proven to be a more reliable predictive factor than BMI in estimating early surgical outcomes for patients who underwent LTME. VFO is associated with fewer numbers of retrieved lymph nodes. PMID- 22065108 TI - Role of dendritic cells in progression and clinical outcome of colon cancer. AB - PURPOSE: The dendritic cells (DCs) are key players in the initiation and regulation of immune responses including antitumor immunity. In the current study, we aimed to elucidate the role of different subtypes of DCs infiltrating the tumor stroma and invasive margin for tumor progression and survival of patients with colon cancer. METHODS: The presence of immature (CD1a- and S100 protein+) and mature (CD83- and HLA-DR+) DCs was evaluated by immunohistochemistry in tissue samples from 145 patients with colon cancer. Patients were dichotomized according to the number of DCs in the tumor stroma and invasive margin, and clinical, histological, and survival data were compared between the two groups of patients. RESULTS: The number of the mature CD83+ DCs in the tumor stroma and in the invasive margin significantly correlated with the tumor stage: the lower level of infiltration was found in patients that have advanced tumor stage. The frequency of distant metastases was higher in patients who had lower numbers of immature CD1a+ DCs in tumor stroma and of CD83+ DCs in invasive margin. Patients showing a relatively high number of S100+ DCs in the tumor stroma and HLA-DR+ DCs in the invasive margin had a longer overall survival (p < 0.05). Patients with lower CD83+ DCs infiltration in invasive margin had worse prognosis after surgical therapy compared with those with higher CD83+ DCs infiltration (p = 0.0397). CONCLUSIONS: Our results demonstrate that the infiltration of colon cancer with DCs is related with tumor progression and patient prognosis, suggesting a central role for DCs in controlling local antitumor immunity. PMID- 22065109 TI - The effects of tacrolimus on colonic anastomotic healing in rats. AB - AIM: The aim of this experimental study is to investigate the effects of tacrolimus on colonic anastomotic healing after subcutaneous administration. MATERIALS AND METHODS: Forty Albino-Wistar male rats were divided into two groups, with two equal subgroups each. They all underwent colonic resection followed by a single-layer, inverted colon anastomosis and were injected subcutaneously with either 1 ml of 0.9% NaCl solution or tacrolimus (0.1 mg/kg body weight) depending on their group. Half of the rats were sacrificed on the fourth postoperative day, while the remaining half were sacrificed on the eighth postoperative day. Macroscopical and histological assessment was performed, while anastomotic bursting pressures and the tissue concentrations in hydroxyproline and collagenase I were evaluated. RESULTS: On the fourth postoperative day, the bursting pressures (217.00 +/- 11.12, p < 0.001), the fibroblast activity (2.80 +/- 0.42, p = 0.022), the neoangiogenesis (2.10 +/- 0.32, p = 0.007) and the tissue hydroxyproline concentration (254.23 +/- 67.10, p = 0.001) were significantly higher in the tacrolimus-treated animals. Furthermore, tacrolimus significantly decreased the inflammatory cell infiltration (1.50 +/- 0.53, p < 0.001) and the tissue collagenase I concentration (4.16 +/- 0.76, p = 0.002). On the eighth day, the bursting pressure (264.00 +/- 32.61, p < 0.001) and the hydroxyproline tissue concentration (331.04 +/- 55.56, p = 0.002) were significantly higher in the tacrolimus subgroups. The inflammatory cell infiltration (1.20 +/- 0.42, p < 0.001) and the collagenase I concentration (1.61 +/- 0.83, p < 0.001) were significantly lower. In addition, the adhesion formation score was significantly lower (1.20 +/- 0.92, p = 0.065). CONCLUSION: Tacrolimus, when injected subcutaneously, promotes healing of colonic anastomoses in rats. It impairs not only inflammatory response but also collagen degradation, resulting to increased anastomotic strength on the fourth as well as on the eighth postoperative day. PMID- 22065110 TI - Dukes C colorectal cancer: is the metastatic lymph node ratio important? AB - PURPOSE: Although the regional lymph node status is essential for staging of colorectal cancer, the importance of the total number of collected nodes remains controversial. Our aim was to examine the impact of the metastatic lymph node ratio (LNR) on the survival of patients with Dukes C colorectal cancer. METHODS: All patients with Dukes C histology were selected from a prospectively collected database of all colorectal cancers resected between 1997 and 2007 at our institution. Demographic, histopathological and adjuvant treatment data were collected. The total number of positive lymph nodes was divided by the total number of lymph nodes examined to calculate the LNR. Patients were categorised into LNR groups 1 to 5 according to cut-off points: <=0.1, 0.21, 0.36, 0.6 and >=0.61. Survival from the date of operation was calculated using Kaplan-Meier estimates. Multivariate analysis was performed to identify those factors influencing survival. RESULTS: Of 1,098 patients who underwent colorectal cancer resections, 41% were staged as Dukes C. Sixty-four percent of patients received chemotherapy. The median number of lymph nodes harvested and positive for tumour were 11 (range 1-52) and 4 (range 1-28), respectively. In patients who received chemotherapy, 5-year survival was 69.3% for LNR 1 and 23.6% for LNR 5. When no chemotherapy was given, the 5-year survival was 43.1% for LNR 1 and 8.7% for LNR 5. CONCLUSIONS: Current evaluation of positive lymph nodes may not accurately stage Dukes C colorectal cancer. The assessment of the LNR is a useful prognostic method in this heterogenous group of patients. PMID- 22065111 TI - Pleiotrophin is a potential colorectal cancer prognostic factor that promotes VEGF expression and induces angiogenesis in colorectal cancer. AB - PURPOSE: Pleiotrophin (PTN) is an important developmental secretory cytokine expressed in many types of cancer and involved in angiogenesis and tumor growth; however, the significance of PTN expression in colorectal cancer (CRC) has not been established. METHODS: Immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect PTN expression in CRC patients. The relationship between PTN expression and clinicopathological characteristics and survival time was statistically analyzed, and the relationship between PTN and vascular endothelial growth factor (VEGF) in tumor angiogenesis was further analyzed. RESULTS: Of CRC tissues, 74.70% (62/83) stained positive, with a strong positive ratio of 60.24% (50/83). The expression of PTN in CRC tissues was much higher than in normal colorectal tissues. PTN serum levels in CRC patients (mean = 254.59 +/- 261.76 pg/ml) were significantly higher than those of normal volunteers (mean = 115.23 +/- 79.53 pg/ml; p < 0.001). PTN expression was related to CRC differentiation and TNM staging. High level of PTN is a predictor of a poor prognosis and high expression of PTN is accompanied by high expression of VEGF in CRC patients. Investigation of the relationship between PTN and VEGF revealed that PTN, through the PTN/RPTPbeta/zeta signaling pathway, increased tyrosine phosphorylation of beta-catenin, leading to an increase in VEGF. CONCLUSIONS: Our study identifies PTN as an essential growth factor for CRC. PTN promotes VEGF expression and cooperates with VEGF in promoting CRC angiogenesis. PTN could serve as a prognostic factor for this cancer. Considering that PTN shows very limited expression in normal tissue, it may represent an attractive new target for CRC therapy. PMID- 22065112 TI - The JAK2 variant rs10758669 in Crohn's disease: altering the intestinal barrier as one mechanism of action. AB - PURPOSE: The aetiology of intestinal barrier dysfunction in Crohn's disease (CD) is poorly understood. Associations in relatives of CD families suggest a genetic basis, but the relevant variants are still unknown. We hypothesized that variants in genes occurring in pathways such as autophagy and IL23 signalling might contribute to CD by altering intestinal permeability. METHODS: We analysed five variants (rs10758669 within JAK2, rs744166 within STAT3, rs4958847, rs11747270 and rs13361189 within IRGM) in adult German inflammatory bowel disease patients (CD, n = 464; ulcerative colitis (UC), n = 292) and matched healthy controls (n = 508). These data were correlated with gastrointestinal permeability as assessed by lactulose/mannitol ratio in CD patients (n = 141) in remission. RESULTS: Our data confirm the association between JAK2 rs10758669 (p = 0.026, OR = 1.25, 95% CI = 1.04-1.50) and STAT3 rs744166 (p = 0.04, OR = 0.83, 95% CI = 0.688-0.998) with CD, but not UC. With respect to all the analysed IRGM variants, no association was found to either CD or UC. Among CD patients, an increased intestinal permeability was detected in 65 out of 141 patients (46.1%). Most importantly, patients carrying the C risk allele within JAK2 rs10758669 displayed an increased permeability more often compared with patients without the C allele (p = 0.004). No association with intestinal permeability was found for STAT3 rs744166 and all IRGM variants. CONCLUSIONS: JAK2 rs10758669 and STAT3 rs744166 increase susceptibility for CD. We show that the A>C substitution in rs10758669 of the JAK2 gene is associated with increased intestinal permeability. Altering intestinal barrier function might thus be one mechanism how JAK2 contributes to CD pathogenesis. PMID- 22065113 TI - Capsule endoscopy: comparison of two different reading modes. AB - PURPOSE: Capsule endoscopy (CE) is a very useful tool for the evaluation of the small intestine, but it is time consuming. The aim of this study was to compare evaluation times and detection rates in two different reading modes (single view at a speed of 10 frames per second (fps) and four images simultaneously, i.e., quadview mode at a speed of 20 fps) to find the optimum setting mode for evaluation of CE videos. METHODS: CE videos of 70 patients performed for different indications (obscure bleeding, n = 50; suspected Crohn's disease, n = 10; and suspected or complicated celiac disease, n = 10) were reviewed by investigators A and B in the two different reading modes. RESULTS: The mean evaluation time using single view at 10 fps was 22 min (SD +/- 9.1 min) and 11.9 min (SD +/- 4.8 min) using quadview mode at 20 fps. The detection rates of angiodysplasias, erosions, small ulcers, and small polyps were only discreetly lower using the quadview mode at 20 fps. In Crohn's disease and celiac disease, the essential aspects of inflamed or atrophic mucosa segments were equally detected in both reading modes. In one case of complicated celiac disease with severe erosive jejunitis, a lymphoma-suspect lesion was overlooked in the quadview mode at 20 fps. CONCLUSIONS: It is often possible to read CE videos in quadview mode at a higher speed with even so a high diagnostic yield in a shortened evaluation time. PMID- 22065114 TI - Long-term follow-up of patients undergoing adipose-derived adult stem cell administration to treat complex perianal fistulas. AB - PURPOSE: In patients with perianal fistulas, administration of adult stem cells (ASCs) derived from liposuction samples has proved a promising technique in a preceding phase II trial. We aimed to extend follow-up of these patients with this retrospective study. METHOD: Patients who had received at least one dose of treatment (ASCs plus fibrin glue or fibrin glue alone) were included. Adverse events notified since the end of the phase II study were recorded. Clinical and magnetic resonance imaging (MRI) criteria were used to determine whether recurrence of the healed fistula had occurred. RESULTS: Data were available for 21 out of 24 patients treated with ASCs plus fibrin glue and 13 out of 25 patients treated with fibrin glue in the phase II study. Follow-up lasted a mean of 38.0 and 42.6 months, respectively. Two adverse events unrelated to the original treatment were reported, one in each group. There were no reports of anal incontinence associated with the procedure. Of the 12 patients treated with ASCs plus fibrin glue who were included in the retrospective follow-up in the complete closure group, only 7 remained free of recurrence. MRI was done in 31 patients. No relationship was detected between MRI results and the clinical fistula status, independent of the treatment received. CONCLUSIONS: Long-term follow-up reaffirmed the very good safety profile of the treatment. Nevertheless, a low proportion of the stem cell-treated patients with closure after the procedure remained free of recurrence after more than 3 years of follow-up. PMID- 22065115 TI - 6-Benzyl 4-ethyl 2-chloro-5,6,7,8-tetra-hydro-pyrido[4,3-d]pyrimidine-4,6-di carboxyl-ate. AB - In the title compound, C(18)H(18)ClN(3)O(4), the dihedral angle between the pyrimidine ring and the N-bonded ester grouping is 56.27 (7) degrees and the dihedral angle between the aromatic rings is 11.23 (7) degrees . PMID- 22065116 TI - First clinical evaluation of a novel capacitive ECG system in patients with acute myocardial infarction. AB - OBJECTIVE: The ECG plays a central role in the rapid diagnosis of acute myocardial infarctions (MI). In haemodynamically instable patients, adhesion of electrodes sometimes is difficult and assessing ECGs through layers of clothes has not been done so far. A novel capacitive measurement of ECG signals is possible without skin contact. Whether this technical innovation can be used in patients with MI is unclear. METHODS: We evaluated a capacitive ECG system (cECG) in patients with anterior and inferior ST elevation MI (STEMI) as compared to patients without ST elevations in anterior and inferior leads. The cECG was assessed using a sensor array consisting of 15 electrodes of which the classical leads I, II, III, aVL, aVF and V(1)-V(3) were calculated from. 66 patients were included in the study. In addition to the conventional ECG (kECG) the novel cECG was registered before reperfusion therapy was started. RESULTS: In a first round, 19 patients presented with anterior MI, 23 with inferior MI, and 7 either with left bundle branch block or lateral MI. Regarding anterior MI, a significant correlation (P < 0.05) was found between ST elevations in leads I, aVL, V(2) and V(3) comparing cECG and kECG. In inferior MI, there was only a significant correlation (P < 0.05) in lead III between cECG and kECG, but not in II and aVF. Therefore, 17 additional patients were included in the study by placing an additional electrode further away from the sensor array on the chest. ST elevations now correlated in all inferior leads II, III and aVF (P < 0.05) as measured in 9 patients with inferior MI. In addition, in 8 patients an inferior MI was correctly ruled out. CONCLUSION: It is possible to identify STEMIs by cECG. This innovative technique could play an important role in the pre-hospital period as well as in the hospital. PMID- 22065117 TI - Aqua-chloridobis(2-eth-oxy-6-formyl-phenolato-kappaO,O)chromium(III) acetonitrile hemisolvate. AB - In the mononuclear complex mol-ecule of the title compound, [Cr(C(9)H(9)O(3))(2)Cl(H(2)O)].0.5CH(3)CN, the Cr(III) atom displays an elongated octa-hedral coordination geometry. The dihedral angle between the benzene rings is 12.27 (11) degrees . Adjacent complex mol-ecules are linked into dimers by O H?O hydrogen bonds, generating rings of R(1) (2)(6) and R(1) (2)(5) graph-set motifs, and by aromatic pi-pi stacking inter-actions, with a centroid-centroid distance of 3.812 (2) A. The crystal packing is further stabilized by inter molecular C-H?N hydrogen bonds. The C and N atoms of the acetonitrile solvent mol ecule are located on a crystallographic twofold axis. PMID- 22065118 TI - 5-Hy-droxy-3-phenyl-5-trifluoro-meth-yl-4,5-dihydro-1H-pyrazole. AB - The five-membered dihydro-pyrazole ring in the title compound, C(10)H(9)F(3)N(2)O, is approximately planar (r.m.s. deviation 0.111 A for all non H atoms) and its phenyl substituent is aligned at an angle of 14.7 (2) degrees . Adjacent mol-ecules are linked by N-H?O and O-H?N hydrogen bonds, generating ribbons running along the b axis of the monoclinic unit cell. PMID- 22065119 TI - Diiodido(1,10-phenanthroline-5,6-dione-kappaN,N')mercury(II). AB - The Hg(II) atom in the title complex, [HgI(2)(C(12)H(6)N(2)O(2))], is tetra hedrally coordinated by the N atoms of the chelating 1,10-phenanthroline-5,6 dione ligand and two I atoms. The range of tetra-hedral angles is broad, viz. 68.94 (17) degrees for the chelate angle to a wide 132.627 (15) degrees for the I-Hg-I angle. The ligand mol-ecule is non-planar with the O atoms lying 0.422 (5) and -0.325 (5) A out of the plane through the remaining atoms [r.m.s. deviation = 0.068 A]. Mol-ecules are consolidated in the crystal packing by C-H?O inter actions. PMID- 22065120 TI - (Z)-Methyl 2-[(4-bromo-2-formyl-phen-oxy)meth-yl]-3-o-tolyl-acrylate. AB - In the title compound, C(19)H(17)BrO(4), the dihedral angle between the two benzene rings is 82.1 (1) degrees . The mol-ecular structure is stabilized by an intra-molecular C-H?O hydrogen bond which generates an S(7) ring motif. The crystal packing is stabilized by inter-molecular C-H?O hydrogen bonds and C-H?pi inter-actions. Inter-molecular C-H?O inter-actions are involved in the formation of centrosymmetric R(2) (2)(16) dimers, which are connected into supra-molecular tapes running along the [100] direction. PMID- 22065121 TI - Rapid improvement of a complex migrainous episode with sodium valproate in a patient with CADASIL. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited disease of small arteries caused by mutations in the Notch3 gene. Complex migrainous episodes, such as acute confusional migraine, status migrainosus with persisting aura, and "CADASIL coma" have been described in patients with CADASIL. However, there are few descriptions of effective treatment of such episodes. We describe a 44-year-old male with CADASIL, who presented with sudden-onset aphasia and decreased responsiveness after prolonged, severe migraine attack. Subsequently, the patient had two generalized seizures. A subtle status epilepticus was suspected because of drowsiness and seizures, and intravenous sodium valproate medication was initiated. EEG recording showed left hemispheric attenuation but no spike discharges, thus not confirming epileptic mechanism. The clinical status of the patient improved markedly after the initiation of valproate. The patient started speaking again; drowsiness and headache subsided. In repeated EEG recording, the left hemispheric attenuation disappeared. Diffusion weighted MR imaging showed no signs of recent ischemic events. The patient recovered fully from the episode with no further seizures. We suggest that CADASIL patients with acute complex migrainous episodes may benefit from intravenous sodium valproate. PMID- 22065122 TI - (E)-2-{1-[(6-Chloro-pyridin-3-yl)meth-yl]imidazolidin-2-yl-idene}-2-cyano-N-(2 methylphenyl)acetamide. AB - In the title compound, C(19)H(18)N(5)O, the imidazolidine ring makes dihedral angles of 87.62 (17) and 28.27 (11) degrees with the pyridine and benzene rings, respectively. An intra-molecular N-H?O hydrogen bond is observed between the carbonyl O atom and an imidazolidine H atom. In the crystal, an inter-molecular N H?N hydrogen bond gives rise to a linear chain running along the b axis. PMID- 22065123 TI - Poly[aqua-(MU(3)-2-hy-droxy-5-nitro-benzoato-kappaO:O:O)rubidium]. AB - In the structure of title compound, [Rb(C(7)H(4)NO(5))(H(2)O)](n), the centrosymmetric cyclic dimeric repeating unit comprises two irregular RbO(4) complex centres bridged by the carboxyl-ate groups of the 5-nitro-salicylate ligands. The coordination about each Rb atom is completed by a monodentate water mol-ecule and a phenolic O-atom donor which gives a bridging extension [Rb-O range = 3.116 (7)-3.135 (5) A]. The polymeric structure is stabilized by inter molecular water O-H?O(carboxyl-ate) hydrogen bonds and weak inter-ring pi-pi inter-actions [minimum ring centroid separation = 3.620 (4) A]. An intramolecular O-H?O hydrogen bond between phenol and carboxylate groups is also present. PMID- 22065124 TI - Water based microwave assisted extraction of thiamethoxam residues from vegetables and soil for determination by HPLC. AB - A microwave assisted extraction (MAE) method for determination of thiamethoxam residues in vegetable and soil samples was standardized. Insecticide spiked vegetable and soil samples were extracted by MAE using water as an extraction solvent, cleaned up by solid phase extraction and analysed by high performance liquid chromatography on photodiode array detector. The recoveries of the insecticide from various vegetable (tomato, radish, brinjal, okra, French been, sugarbeet) and soil (sandy loam, silty clay loam, sandy clay loam, loamy sand) samples at 0.1 and 0.5 MUg g(-1) spiking levels ranged from 79.8% to 86.2% and from 82.1% to 87.0%, respectively. The recoveries by MAE were comparable to those obtained by the conventional blender and shake-flask extraction techniques. The precision of the MAE method was demonstrated by relative standard deviations of <3% for the insecticide. PMID- 22065125 TI - Methylmercury concentrations in six fish species from two Colombian rivers. AB - The objective of this study was to determine whether fish collected from the La Miel or Nechi Rivers (Colombia) differed in muscle methyl mercury (meHg) concentration. Two fish from six different species were collected from markets adjacent to each river. Overall, fish collected from the market adjacent to the Nechi River contained higher levels of meHg. This result however is being driven by very high meHg concentrations in four individual fish, three of which are Pimelodid, long-whiskered catfish. These catfish may represent ideal sentinel organism for the detection of meHg contamination in Colombian rivers. PMID- 22065126 TI - Persistence and dissipation of the insecticide flubendiamide and its metabolite desiodo flubendiamide residues in tomato fruit and soil. AB - A method for residue analysis of flubendiamide and its metabolite desiodo flubendiamide was developed using high performance liquid chromatography. This method was then used to evaluate the residual level and dissipation rate of flubendiamide and desiodo flubendiamide in the tomato fruit. The half-life of flubendiamide in tomato fruit was 1.64 and 1.98 days in recommended and double of the recommended dose, respectively. Tomato fruit and soil samples analyzed on the 10th day after the last spray revealed that flubendiamide and its metabolite desiodo flubendiamide residues at below determination level (0.01 MUg g(-1)) at either dose of application. PMID- 22065127 TI - Weather conditions and political party vote share in Dutch national parliament elections, 1971-2010. AB - Inclement weather on election day is widely seen to benefit certain political parties at the expense of others. Empirical evidence for this weather-vote share hypothesis is sparse however. We examine the effects of rainfall and temperature on share of the votes of eight political parties that participated in 13 national parliament elections, held in the Netherlands from 1971 to 2010. This paper merges the election results for all Dutch municipalities with election-day weather observations drawn from all official weather stations well distributed over the country. We find that the weather parameters affect the election results in a statistically and politically significant way. Whereas the Christian Democratic party benefits from substantial rain (10 mm) on voting day by gaining one extra seat in the 150-seat Dutch national parliament, the left-wing Social Democratic (Labor) and the Socialist parties are found to suffer from cold and wet conditions. Cold (5 degrees C) and rainy (10 mm) election day weather causes the latter parties to lose one or two parliamentary seats. PMID- 22065128 TI - 2-[(E)-(6-Amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra-hydro-pyrimidin-5-yl)imino meth-yl]pyridinium chloride monohydrate. AB - The title compound, C(12)H(14)N(5)O(2) (+).Cl(-).H(2)O, is the monohydrate of the hydro-chloride of an oxopurine-derived Schiff base in which protonation took place at the pyridine N atom. The organic cation is essentially planar (r.m.s. of all fitted non-H atoms = 0.0373 A). In the crystal, N-H?O and N-H?Cl hydrogen bonds as well as C-H?O and C-H?Cl contacts connect the different entities into a three-dimensional network. The shortest centroid-centroid distance between two pyrimidine rings is 3.6364 (9) A. PMID- 22065129 TI - 1,5-Dichloro-3(2,7),7(2,7)-dinaphthal-ena-2,4,6,8-tetra-oxa-1(2,6),5(2,6) di(1,3,5-triazina)octa-phane. AB - In the macrocyclic title compound, C(26)H(12)Cl(2)N(6)O(4), an O-atom-bridged calix[2]naphthalene-[2]triazine synthesized using a one-pot approach from naphthalene-2,7-diol and cyanuric chloride, the two isolated naphthalene planes and the two triazine-2,6-di-oxy planes adopt a 1,3-alternate configuration, with a dihedral angle of 84.10 (8) degrees between the naphthalene rings and a dihedral angle of 39.02 (14) degrees between the triazine rings. In the crystal, weak inter-molecular pi-pi stacking inter-actions are found between face-to-face naphthalene rings [centroid-centroid distance = 3.662 (7) A]. PMID- 22065130 TI - 3,4-Dibromo-2,5-dimethyl-1-phenyl-sulfonyl-1H-pyrrole. AB - In the title compound, C(12)H(11)Br(2)NO(2)S, the dihedral angle between the two rings is 78.79 (12) degrees . The crystal packing features C-H?pi inter-actions. PMID- 22065131 TI - 3-(2-Bromo-acet-yl)-6-fluoro-2H-chromen-2-one. AB - The non-H atoms of the title compound, C(11)H(6)BrFO(3), are essentially coplanar (r.m.s. deviation for all non-H atoms = 0.074 A). In the crystal, the molecules are linked by C-H?O and C-H?Br inter-actions. PMID- 22065132 TI - N-(2-Chloro-phen-yl)-4-methyl-benzamide. AB - The asymmetric unit of the title compound, C(14)H(12)ClNO, contains two independent mol-ecules in which the dihedral angles between the two aromatic rings are 51.76 (6) and 51.48 (7) degrees . The crystal structure is stabilized by inter-molecular N-H?O hydrogen bonds, which link the mol-ecules into chains running along the c axis. PMID- 22065133 TI - [1-(1H-Imidazo[4,5-f][1,10]phenanthro-lin-2-yl)naphthalen-2-ol kappaN,N]diiodidomercury(II). AB - In the title compound, [HgI(2)(C(23)H(14)N(4)O)], the Hg(II) atom is four coordinated by two N atoms from one 1-(1H-imidazo[4,5-f][1,10]phenanthrolin-2 yl)naphthalen-2-ol ligand and by two I atoms in a distorted tetra-hedral environment. An intra-molecular O-H?N hydrogen bond stabilizes the mol-ecular conformation and an inter-molecular N-H?I inter-action stabilizes the crystal packing. PMID- 22065135 TI - 5-Chloro-1-phenyl-1H-pyrazol-4-amine. AB - In the crystal structure of the title compound, C(9)H(8)ClN(3), amino-pyrazole N H?N hydrogen bonds connect the mol-ecules along the [010] direction; the chains interact with each other only by van der Waals-type inter-actions. The pyrazole and phenyl rings are inclined at a dihedral angle of 45.65 (6) degrees PMID- 22065136 TI - cis-Aqua-bis-(2,2'-bipyrimidine-kappaN,N)iodidomanganese(II) iodide dihydrate. AB - The asymmetric unit of the title compound, [MnI(C(8)H(6)N(4))(2)(H(2)O)]I.2H(2)O, contains a cationic Mn(II) complex, an I(-) anion and two solvent water mol ecules. In the complex, the Mn(II) ion is six-coordinated in a considerably distorted octa-hedral environment defined by four N atoms of the two chelating 2,2'-bipyrimidine (bpym) ligands, one I(-) anion and one O atom of a water ligand. As a result of the different trans effects of the I and O atoms, the Mn-N bond trans to the I atom is slightly longer than the Mn-N bond trans to the O atom. The dihedral angle between the least-squares planes of the two bpym ligands [maximum deviation = 0.088 (4) A] is 76.48 (6) degrees . In the crystal, the complex cation, the anion and the solvent water mol-ecules are linked by inter molecular O-H?O, O-H?I and O-H?N hydrogen bonds. PMID- 22065134 TI - GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS. AB - Inhibiting glycogen synthase kinase-3 (GSK-3) activity via pharmacological intervention has become an important strategy for treating neurodegenerative and psychiatric disorders. The known GSK-3 inhibitors are of diverse chemotypes and mechanisms of action and include compounds isolated from natural sources, cations, synthetic small-molecule ATP-competitive inhibitors, non-ATP-competitive inhibitors, and substrate-competitive inhibitors. Here we describe the variety of GSK-3 inhibitors with a specific emphasis on their biological activities in neurons and neurological disorders. We further highlight our current progress in the development of non-ATP-competitive inhibitors of GSK-3. The available data raise the hope that one or more of these drug design approaches will prove successful at stabilizing or even reversing the aberrant neuropathology and cognitive deficits of certain central nervous system disorders. PMID- 22065137 TI - Chloroquine-related depression. AB - Drugs are known to induce depressive states. Chloroquine, an antimalarial, in therapeutic doses administered for malaria therapy, may produce symptoms rather indistinguishable from endogenous depression. The possible mechanisms of production of depression related to chloroquine use are hypothesised. PMID- 22065138 TI - 8-Thia-1,6-diaza-bicyclo-[4.3.0]nonane-7,9-dione. AB - There are two independent mol-ecules, A and B, in the asymmetric unit of the title compound, C(6)H(8)N(2)O(2)S. In the crystal, pairs of inter-molecular S?O contacts [3.286 (1) A] link the B mol-ecules into inversion dimers. PMID- 22065139 TI - (E)-4-Phenyl-butan-2-one oxime. AB - In the title compound, C(10)H(13)NO, the C-C-C-C torsion angle formed between the benzene ring and the butan-2-one oxime unit is 73.7 (2) degrees , with the latter lying above the plane through the benzene ring. In the crystal, inter-molecular O H?N hydrogen bonds link pairs of mol-ecules into dimers, forming R(2) (2)(6) ring motifs which are stacked along the a axis. PMID- 22065140 TI - N'-(3,5-Dibromo-2-hy-droxy-benzyl-idene)-4-nitro-benzohydrazide methanol monosolvate. AB - The title compound, C(14)H(9)Br(2)N(3)O(4).CH(4)O, was obtained as the product of the reaction of 3,5-dibromo-salicyl-aldehyde with 4-nitro-benzohydrazide in methanol. The benzohydrazide mol-ecule is nearly planar, with a maximum deviation of 0.126 (2) A. The mean planes of the two benzene rings make a dihedral angle of 9.3 (3) degrees . Intra-molecular O-H?N and O-H?Br inter-actions are observed in the benzohydrazide mol-ecule. In the crystal, pairs of adjacent benzohydrazide mol-ecules are linked by two methanol mol-ecules through inter-molecular O-H?O and N-H?O hydrogen bonds, forming a dimer. PMID- 22065141 TI - Therapeutic monoclonal antibodies for multiple myeloma: an update and future perspectives. AB - Multiple myeloma (MM) still remains incurable in most of the patients. Despite of treatments with high-dose chemotherapy, stem cell transplantation and other novel therapies, most patients will become refractory to the therapies and relapse. Thus, it is urgent to develop new approaches for MM treatment. Currently, antibody-targeted therapy has been extensively utilized in hematological malignancies, including MM. Several novel monoclonal antibodies (mAbs) against MM have been generated and developed over the past several years. These mAbs aim to target not only tumor cells alone but also tumor microenvironment, including interaction of tumor-bone marrow stromal cells and the components of bone marrow milieu, such as cytokines or chemokines that support myeloma cell growth and survival. These include mAbs specific for CD38, CS1, CD40, CD74, CD70, HM1.24, interleukin-6 and beta(2)-microglobulin (beta(2)M). We have shown that anti beta(2)M mAbs may be a potential antitumor agent for MM therapy due to their remarkable efficacy to induce myeloma cell apoptosis in tumor cell lines and primary myeloma cells from patients in vitro and in established myeloma mouse models. In this article, we will review advances in the development and mechanisms of MM-targeted mAbs and especially, anti-beta(2)M mAbs. We will also discuss the potential application of the mAbs as therapeutic agents to treat MM. PMID- 22065142 TI - Dimeth-yl(4-methyl-phen-yl)ammonium naphthalene-1,5-disulfonate dihydrate. AB - The asymmetric unit of the organic-inorganic hybrid salt, 2C(9)H(14)N(+).C(10)H(6)O(6)S(2) (2-).2H(2)O, consists of one dimeth-yl(4-methyl phen-yl)ammonium cation, one half of a naphthalene-1,5-disulfonate anion lying on a crystallographic centre of inversion, and one water mol-ecule. In the crystal, O-H?O(S) and N-H?OH(2) hydrogen bonds link the cations and anions forming ring motifs. PMID- 22065143 TI - An equity framework for health technology assessments. AB - Despite the inclusion of equity in the design of many health care systems, pragmatic tools for considering equity systematically, alongside the efficiency categories of cost-effectiveness in health technology assessment (HTA), remain underdeveloped. This article develops a framework to help decision makers supplement the standard efficiency criteria of HTA and avoid building inequities, explicit or implicit, into their methods. The framework is intended as a first step toward creating a checklist for alerting decision makers to a wide range of equity considerations for HTA. This framework is intended be used as part of the process through which advisory bodies receive their terms of reference; scope the agenda prior to the selection of a candidate intervention and its comparators for HTA; prepare background briefing for decision makers; and help to structure the discussion and composition of professional and lay advisory groups during the assessment process. The framework is offered as only a beginning of an ongoing process of deliberation and consultation, through which the matters covered can be expected to become more comprehensive and the record of past decisions and their contexts in any jurisdiction adopting the tool can serve to guide subsequent evidence gathering and decisions. In these ways, it may be hoped that equity will be more systematically and fully considered and implemented in both the procedures and decisions of HTA. PMID- 22065144 TI - Test result-based sampling: an efficient design for estimating the accuracy of patient safety indicators. AB - OBJECTIVE: Accuracy studies of Patient Safety Indicators (PSIs) are critical but limited by the large samples required due to low occurrence of most events. We tested a sampling design based on test results (verification-biased sampling [VBS]) that minimizes the number of subjects to be verified. METHODS: We considered 3 real PSIs, whose rates were calculated using 3 years of discharge data from a university hospital and a hypothetical screen of very rare events. Sample size estimates, based on the expected sensitivity and precision, were compared across 4 study designs: random and VBS, with and without constraints on the size of the population to be screened. RESULTS: Over sensitivities ranging from 0.3 to 0.7 and PSI prevalence levels ranging from 0.02 to 0.2, the optimal VBS strategy makes it possible to reduce sample size by up to 60% in comparison with simple random sampling. For PSI prevalence levels below 1%, the minimal sample size required was still over 5000. CONCLUSIONS: Verification-biased sampling permits substantial savings in the required sample size for PSI validation studies. However, sample sizes still need to be very large for many of the rarer PSIs. PMID- 22065145 TI - Value of magnetic resonance arthrography in post-traumatic anterior shoulder instability prior to arthroscopy: a prospective evaluation of MRA versus arthroscopy. AB - PURPOSE: This prospective study was designed to evaluate the value of magnetic resonance arthrography (MRA) after traumatic anterior shoulder instability prior to arthroscopy. METHODS: Patients included had two or more shoulder dislocations, at least the first being traumatic. MRA images were scored for Hill Sachs lesions, superior labral anterior posterior (SLAP) lesions, rotator cuff tears, glenohumeral ligament (GHL) lesions and Bankart lesions. Consequently, a standardized shoulder arthroscopy was performed. Five surgeons were involved in the study, initially blinded to the MRA results. MRA and arthroscopic findings were compared. Interobserver agreement was calculated by using Cohen's Kappa coefficients (kappa). RESULTS: Eighteen patients (13 male, 5 female) were included (mean age 26.1 years). Hill Sachs lesions demonstrated fair agreement (kappa = 0.33) whereas for SLAP lesions moderate agreement was calculated (kappa = 0.43). On MRA, four partial thickness rotator cuff lesions were seen, not being stated by arthroscopy. GHL lesions were described on MRA in 15 patients; only two patients turned out to have GHL lesions at arthroscopy. Two arthroscopically diagnosed Bankart lesions which needed surgical treatment were not detected by MRA (moderate agreement, kappa = 0.47). CONCLUSIONS: In patients with post traumatic anterior glenohumeral instability MRA shows many lesions that can not be confirmed by arthroscopy and therefore do not have therapeutical consequences. On the other hand some labral lesions which do need surgical treatment are not detected on MRA. At least from this study, it can be concluded that MRA has limited value prior to the arthroscopic treatment of post-traumatic shoulder instability. PMID- 22065146 TI - Primary results of Kienbock's disease treated using balloon kyphoplasty system. AB - OBJECTIVE: Kienbock's disease is difficult to treat and optimal treatments for stages II to III continue to elude investigators. We hypothesized that impacting the ischemic cancellous trabeculae and increasing the strength and rigidity of the lunate with balloon kyphoplasty can prevent lunate collapse, relieve the symptoms, and increase wrist range of motion. The purpose of this study was to demonstrate the feasibility of percutaneous balloon kyphoplasty for treatment of stage II to III Kienbock's disease. METHODS: The study group comprised five patients (two in stage II, three in stage III). All were treated with balloon kyphoplasty. Pain, strength, and wrist flexion/extension range of motion were evaluated preoperatively and postoperatively. The Mayo Wrist Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score were used to evaluate outcomes. Patient satisfaction was also assessed. Comparisons between preoperative and postoperative data were made with SPSS software. RESULTS: Clinical data were collected at a mean of 26.6 months (range 24-28 months) postoperatively. Pain was significantly reduced from 6.8 +/- 0.8 in the visual analog scale preoperatively to 0.6 +/- 0.9 at the 24-month follow-up. Strength and range of motion were improved postoperatively in all patients. The mean DASH score was 11.3 (range 6.7-18.3), and the mean Mayo Wrist Score was 78 (range 75 80). All five patients returned to their previous occupations. CONCLUSIONS: Balloon kyphoplasty can prevent lunate collapse, reduce pain, and improve wrist function of patients with stage II to III Kienbock's disease. Further studies regarding the feasibility of this new approach are warranted. PMID- 22065147 TI - Fenestrated pedicle screws for cement-augmented purchase in patients with bone softening: a review of 21 cases. AB - BACKGROUND: This prospective mixed cohort study was designed to evaluate the middle- to long-term purchase of cement-augmented pedicular screws in patients with poor bone quality. The growing number of surgical procedures performed in the spine has highlighted the problem of screws loosening in patients with poor bone stock due to osteoporosis and/or tumors. Different methods of increasing screw purchase have been reported in the literature, including polymethylmethacrylate (PMMA) augmentation. MATERIALS AND METHODS: From September 2006 to April 2008, 21 patients with a poor bone stock condition due to osteoporosis or tumor underwent posterior stabilization by fenestrated pedicle screws and PMMA augmentation. Pain improvement and long-term clinical outcome were assessed by visual analogue scale (VAS) score and SF-36 health survey (SF 36) questionnaire. Implant stability was evaluated by plain radiography and CT scans performed three days after surgery and every three months thereafter. After the first 12 months, radiologic controls were taken once a year in all surviving patients. Complications were evaluated in all cases. RESULTS: All patients were clinically and radiographically followed up for a mean of 36 months. VAS scores and SF-36 questionnaires showed a statistically significant reduction in pain and improvement in the quality of life. No radiological loosening or pulling out of screws was observed. In two cases, cement leakage occurred intraoperatively: one patient who suffered from a transitory nerve root palsy improved spontaneously, while the surgeon immediately removed the excess cement before setting in the other case. In three cases, the post-op CT scan revealed a small amount of cement in the canal without clinical relevance. CONCLUSIONS: Fenestrated screws for cement augmentation provided effective and lasting purchase in patients with poor bone quality due to osteoporosis or tumors. No case of loosening was recorded after a mean follow-up of 36 months. The only clinical complication strictly related to PMMA screw augmentation did not require further surgery. PMID- 22065148 TI - Medication induced diabetes during induction in pediatric acute lymphoblastic leukemia: prevalence, risk factors and characteristics. AB - INTRODUCTION: Medication induced diabetes (MID) during induction therapy (MIDi) in patients with acute lymphoblastic leukemia (ALL) is not well characterized in children, with recent studies yielding conflicting results. PURPOSE: The purpose of the study was to describe the prevalence of MIDi and risk factors for its development. METHODS: We retrospectively gathered demographic, disease course and treatment data on 363 patients aged 1 to 17.9 years diagnosed with ALL at a pediatric tertiary care hospital between 1998 and 2005. MIDi was defined as blood glucose >=200 mg/dL (11.1 mmol/L) on at least 2 separate days during induction. RESULTS: Fifty-seven subjects (15.7%) developed MIDi during the study period. Patients >=10 years were more likely to develop MIDi than those <10 years (odds ratio [OR] 9.6, 95% confidence interval [CI] 5.1-17.8). BMI percentile among those with MIDi (mean +/- SD 58.2 +/- 31.0) did not differ from those without MIDi (52.2 +/- 32.0, P = 0.429). The presence of Trisomy 21 (OR 3.6, 95% CI 1.1 11.4, P = 0.030) and CNS involvement at diagnosis (OR 3.8, 95% CI 1.4-10.1, P = 0.009) were associated with an increased risk of MIDi. After adjustment for potential confounding variables, age >=10 years and the presence of CNS disease at diagnosis remained significantly associated with MIDi. CONCLUSIONS: Older age and CNS involvement at diagnosis increase the risk of MIDi. In contrast to previous studies, higher BMI was not associated with MIDi in our population. PMID- 22065150 TI - [Fibromyalgia]. PMID- 22065151 TI - Functional centromeres in Astragalus sinicus include a compact centromere specific histone H3 and a 20-bp tandem repeat. AB - The centromere plays an essential role for proper chromosome segregation during cell division and usually harbors long arrays of tandem repeated satellite DNA sequences. Although this function is conserved among eukaryotes, the sequences of centromeric DNA repeats are variable. Most of our understanding of functional centromeres, which are defined by localization of a centromere-specific histone H3 (CENH3) protein, comes from model organisms. The components of the functional centromere in legumes are poorly known. The genus Astragalus is a member of the legumes and bears the largest numbers of species among angiosperms. Therefore, we studied the components of centromeres in Astragalus sinicus. We identified the CenH3 homolog of A. sinicus, AsCenH3 that is the most compact in size among higher eukaryotes. A CENH3-based assay revealed the functional centromeric DNA sequences from A. sinicus, called CentAs. The CentAs repeat is localized in A. sinicus centromeres, and comprises an AT-rich tandem repeat with a monomer size of 20 nucleotides. PMID- 22065152 TI - Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin. AB - Microorganisms have been implicated in the pathogenesis of psoriasis. Previous studies of psoriasis and normal skin have used swabs from the surface rather than skin biopsies. In this study, biopsies were taken from 10 patients with psoriasis and 12 control subjects from unmatched sites. Samples were analysed with massive parallel pyrosequencing on the 454 platform targeting the 16S rRNA gene and the variable regions V3-V4. The samples grouped into 19 phyla, 265 taxon and 652 operational units (OTUs) at 97% identity. A cut-off abundance level was set at 1%. The three most common phyla in both normal and psoriasis skin were Firmicutes (39% psoriasis, 43% normal skin), Proteobacteria (38% psoriasis, 27% normal skin) and Actinobacteria (5% psoriasis, 16% normal skin, p = 0.034). In trunk skin, Proteobacteria were present at significantly higher levels in psoriasis compared to controls (52 vs. 32%, p = 0.0113). The commonest genera were Streptococci in both psoriasis (32%) and normal skin (26%). Staphylococci were less common in psoriasis (5%) than in controls (16%), as were Propionibacteria (psoriasis 0.0001669%, controls 0.0254%). Both Staphylococci and Propionibacteria were significantly lower in psoriasis versus control limb skin (p = 0.051, 0.046, respectively). This study has shown some differences in microbiota between psoriasis and normal skin. Whether these are of primary aetiological significance, or secondary to the altered skin of psoriasis remains to be determined. PMID- 22065153 TI - cis-[1,2-Bis(diphenyl-arsan-yl)ethane-kappaAs,As']tetra-carbonyl-chromium(0). AB - In the title compound, [Cr(C(26)H(24)As(2))(CO)(4)], the Cr atom is octa-hedrally coordinated by four carbonyl ligands and one bidentate 1,2-bis-(diphenyl-arsan yl)ethane ligand, which chelates in a cis manner with an As-Cr-As bite angle of 82.513 (9) degrees . The dihedral angles between the pairs of benzene rings attached to each As atom are 84.63 (9) and 77.15 (8) degrees . In the crystal, mol-ecules are linked by C-H?O inter-actions, forming infinite chains along the a axis. The crystal structure is further stabilized by C-H?pi inter-actions. PMID- 22065154 TI - Growth differentiation factor 15: a canary in a coal mine? PMID- 22065155 TI - Association of growth differentiation factor-15 with coronary atherosclerosis and mortality in a young, multiethnic population: observations from the Dallas Heart Study. AB - BACKGROUND: Growth differentiation factor 15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions. Although higher circulating GDF-15 concentrations are associated with mortality across a spectrum of cardiovascular conditions, the relationship of GDF-15 with atherosclerosis and mortality in the general population remains undefined. METHODS: We measured plasma GDF-15 in 3219 participants of the Dallas Heart Study, a population sample of adults ages 30-65 years (55% women, 49% black). GDF 15 was analyzed in prespecified categories (<1200; 1200-1799; and >=1800 ng/L) and continuously. End points included prevalent coronary artery calcium (CAC>10 Agatston units), increased CAC (CAC>=100 Agatston units) by electron beam computed tomography, and mortality through a median 7.3 years of follow-up (120 deaths, 48 cardiovascular deaths). RESULTS: Increasing GDF-15 associated with older age, black race, hypertension, diabetes, smoking, left ventricular (LV) mass/body surface area, and worse renal function (P<0.0001 for each). In multivariable models adjusted for traditional risk factors, renal function, and LV mass/body surface area, GDF-15>=1800 ng/L was associated with CAC>10 (odds ratio 2.1; 95% CI 1.2-3.7; P=0.01), CAC>=100 (odds ratio 2.6; 95% CI 1.4-4.9; P=0.002), all-cause mortality (hazard ratio 3.5; 95% CI 2.1-5.9, P<0.0001), and cardiovascular mortality (hazard ratio 2.5; 95% CI 1.1-5.8, P=0.03). Adding log GDF-15 to fully adjusted models modestly improved the c statistic (P=0.025), the integrated discrimination index (0.028; P<0.0001) and the category-less net reclassification index (0.42; P=0.002). These findings remained significant with further adjustment for high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T. CONCLUSIONS: GDF-15 is independently associated with subclinical coronary atherosclerosis and mortality, and its potential role for risk stratification in the general population merits further evaluation. PMID- 22065156 TI - Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: the JUPITER trial. AB - BACKGROUND: Although statin therapy is known to increase concentrations of PCSK9, whether this effect is related to the magnitude of LDL reduction is uncertain. This study was undertaken to understand the extent of this effect and examine the relationship between PCSK9 and LDL cholesterol (LDL-C) reduction. METHODS: We measured plasma PCSK9 concentrations by ELISA at baseline and at 1 year in 500 men and 500 women participating in the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial that randomly allocated participants to rosuvastatin 20 mg daily or placebo. We also evaluated rs11591147, a single nucleotide polymorphism known to have an impact on plasma PCSK9 concentrations. RESULTS: At baseline, median (interquartile range) PCSK9 concentrations were higher in women [73 (62-90)] ng/mL than in men [69 (57 81) ng/mL] (P<0.005). During 1 year, there was no change in PCSK9 concentrations in the placebo arm, suggesting stability in time. In contrast, the rosuvastatin increased PCSK9 by 35% in women [101 (82-117) ng/mL] and 28% in men [89 (71-109) ng/mL] (P<0.0001). Among those allocated to rosuvastatin, greater reductions in LDL-C were associated with greater increases in PCSK9 on both absolute and relative scales (r=-0.15, P<0.0005). Furthermore PCSK9 (rs11591147) did not alter the magnitude of LDL-C reduction associated with rosuvastatin use. CONCLUSIONS: In this randomized trial, rosuvastatin increased plasma concentration of PCSK9 in proportion to the magnitude of LDL-C reduction; the LDL-C response to statin could not be inferred by PCSK9 concentrations. PMID- 22065157 TI - Midregional proadrenomedullin for prediction of cardiovascular events in coronary artery disease: results from the AtheroGene study. AB - BACKGROUND: Midregional proadrenomedullin (MR-proADM) is a newly identified prognostic marker in heart failure. We evaluated the prognostic impact of MR proADM in a cohort of patients with symptomatic coronary artery disease according to their clinical presentation. METHODS: We measured baseline MR-proADM concentrations in 2240 individuals from the prospective AtheroGene study and evaluated the prognostic impact on future fatal and nonfatal cardiovascular events during a follow-up period of 3.6 (1.6) years. RESULTS: The sample comprised 1355 individuals with stable angina pectoris (SAP) and 885 with acute coronary syndrome (ACS). A cardiovascular event occurred in 192 people. Individuals presenting with SAP had only slightly lower plasma MR-proADM concentrations than those with ACS (0.53 vs 0.55 nmol/L, P=0.006). MR-proADM showed a moderate association with age, serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), glomerular filtration rate, serum C-reactive protein, hypertension, diabetes, and prevalent multivessel disease (all P<0.0005). Individuals suffering from a cardiovascular event had higher MR-proADM concentrations at baseline in both groups (SAP 0.63 vs 0.53 nmol/L and ACS 0.65 nmol/L vs 0.55 nmol/L, both P<0.0005). Cox regression analysis incorporating various variables of cardiovascular risk and NT-proBNP revealed a hazard ratio of 1.4 (95% CI 1.2-1.6; P<0.0005) per increment of MR-proADM by 1SD. In risk models for secondary prevention, MR-proADM provided information comparable to that of NT proBNP. CONCLUSIONS: MR-proADM is an independent predictor for future cardiovascular events in patients with symptomatic coronary artery disease, providing information comparable to NT-proBNP for secondary risk stratification. PMID- 22065158 TI - Facial recognition software success rates for the identification of 3D surface reconstructed facial images: implications for patient privacy and security. AB - Image de-identification has focused on the removal of textual protected health information (PHI). Surface reconstructions of the face have the potential to reveal a subject's identity even when textual PHI is absent. This study assessed the ability of a computer application to match research subjects' 3D facial reconstructions with conventional photographs of their face. In a prospective study, 29 subjects underwent CT scans of the head and had frontal digital photographs of their face taken. Facial reconstructions of each CT dataset were generated on a 3D workstation. In phase 1, photographs of the 29 subjects undergoing CT scans were added to a digital directory and tested for recognition using facial recognition software. In phases 2-4, additional photographs were added in groups of 50 to increase the pool of possible matches and the test for recognition was repeated. As an internal control, photographs of all subjects were tested for recognition against an identical photograph. Of 3D reconstructions, 27.5% were matched correctly to corresponding photographs (95% upper CL, 40.1%). All study subject photographs were matched correctly to identical photographs (95% lower CL, 88.6%). Of 3D reconstructions, 96.6% were recognized simply as a face by the software (95% lower CL, 83.5%). Facial recognition software has the potential to recognize features on 3D CT surface reconstructions and match these with photographs, with implications for PHI. PMID- 22065159 TI - Splenectomy enhances the anti-fibrotic effect of bone marrow cell infusion and improves liver function in cirrhotic mice and patients. AB - BACKGROUND: In 2003, we initiated a clinical trial to examine autologous bone marrow cell infusion (ABMi) therapy for cirrhotic patients and reported the clinical effect of the therapy. To analyze how splenectomy may potentiate the effects of bone marrow cell infusion on cirrhosis, we performed a mouse study and a clinical trial on patients with cirrhosis. METHODS: In mice, we analyzed the effect of splenectomy on bone marrow cell infusion in four experimental groups (group A, splenectomy + bone marrow cell infusion + CCl(4); group B, sham operation + bone marrow cell infusion + CCl(4); group C, splenectomy + CCl(4); group D, sham operation + CCl(4)). In clinical, we compared the effect of splenectomy on ABMi therapy. RESULTS: We observed significantly increased average serum albumin levels and higher expression of green fluorescent protein (GFP), matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen in the livers of group A. We observed MMP9/GFP double-positive cells in the cirrhotic livers. A significant decrease in the liver fibrosis areas was observed in group A. Splenectomy enhanced the repopulation of bone marrow cells into the cirrhotic liver and improved the liver microenvironment via expression of MMP9 secreted from repopulating GFP-positive cells. Next, we performed a clinical trial to compare the effect of splenectomy on the efficacy of ABMi therapy. Cirrhotic patients who underwent splenectomy before ABMi therapy tended to have a greater improvement in liver function. CONCLUSION: ABMi therapy with splenectomy may be an effective therapeutic modality for cirrhosis. PMID- 22065160 TI - A large-scale nationwide multicenter prospective observational study of triple therapy using rabeprazole, amoxicillin, and clarithromycin for Helicobacter pylori eradication in Japan. AB - BACKGROUND: In recent years in Japan, the rate of clarithromycin (CAM) resistance in Helicobacter pylori has risen to around 30%, and the eradication rate with triple therapy [proton pump inhibitor + amoxicillin (AMPC) + CAM] has been trending downward to around 70%. In 2007, rabeprazole (RPZ)-based triple therapy (RPZ + AMPC + CAM: RAC therapy) was approved in Japan, and a large-scale nationwide study was therefore initiated to evaluate the efficacy and safety of RAC therapy in clinical practice. METHODS: Patients with H. pylori-positive gastric/duodenal ulcer (including ulcer scars) were administered triple therapy comprising RPZ 10 mg, AMPC 750 mg, and CAM 200 mg (or 400 mg), twice daily for 7 days. RESULTS: The eradication rate was 80.7% (2,551/3,162). The results of multivariate analysis indicated the following as factors affecting the eradication rate: sex, treatment compliance, history of H. pylori treatment, presence of urologic disease, presence of respiratory disease, and year of starting treatment. The incidence of adverse drug reactions (such as diarrhea and dysgeusia) was 4.4% (166/3,789). The results of multivariate analysis indicated the following as factors affecting the incidence of adverse drug reactions: sex, daily CAM dose, and history of allergies. CONCLUSION: In a large-scale nationwide study of use in clinical practice, RAC therapy was confirmed to be effective and safe. PMID- 22065161 TI - Usefulness of differentiating metabolic syndrome into visceral fat type and subcutaneous fat type using ultrasonography in Japanese males. AB - BACKGROUND: Although metabolic syndrome (MS) is likely to be associated with nonalcoholic fatty liver disease (NAFLD), visceral fat type MS and subcutaneous fat type MS have not been distinguished. In this study, we divided persons with MS into those with visceral and subcutaneous fat types by ultrasonography (US), and elucidated differences between these types of MS in Japanese males. METHODS: The subjects were 628 males with MS who underwent a medical checkup including abdominal US. We examined for the presence of fatty liver and investigated biochemical parameters, and we also made a distinction between visceral and subcutaneous fat types of MS by US. RESULTS: Total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the frequency of fatty liver were significantly higher in visceral fat type MS than in subcutaneous fat type MS. On logistic regression analysis with NAFLD (in our study, fatty liver with ALT >=31 IU/l was defined as NAFLD) as a dependent variable, the age, body mass index (BMI), AST, and visceral fat type MS were significant risk factors for NAFLD. BMI, AST, and visceral fat type MS were predictors of an increased prevalence of NAFLD [odds ratios (ORs) = 1.903, 12.06, and 2.617; 95% confidence intervals (CIs) = 1.122-3.228, 7.053-20.61, and 1.741-3.935; p = 0.017, <0.001, and <0.001, respectively). CONCLUSIONS: Japanese males with visceral fat type MS are more likely to have dyslipidemia, fatty liver, and liver dysfunction than those with subcutaneous fat type MS. Visceral fat type MS is one of the most significant risk factors for NAFLD in Japanese males with MS. PMID- 22065162 TI - Acoustic radiation force impulse elastography for noninvasive assessment of chronic pancreatitis. AB - BACKGROUND: Endoscopic ultrasonography or real-time elastography has been applied for the diagnosis of chronic pancreatitis. Acoustic radiation force impulse (ARFI) imaging is another tissue strain imaging technology, and recent technological advances have enabled quantification of the stiffness of some tissues by measuring the shear wave velocity (SWV) during routine B-mode ultrasonography. METHODS: ARFI elastography was performed in 52 healthy volunteers and 46 patients with chronic pancreatitis. SWV was measured in the head, body, and tail of the pancreas. The diagnostic performance was assessed using receiver-operating characteristic (ROC) curves. RESULTS: SWV in patients with chronic pancreatitis was significantly higher than that in healthy volunteers in each part of the pancreas, although the measurement was difficult in the tail of the pancreas. The area under the ROC curve was 0.78 in the body of the pancreas, with an optimal cut-off value of 1.40 m/s, and the sensitivity, specificity, positive predictive value, and negative predictive value were 75, 72, 69, and 78%, respectively. In the patients with chronic pancreatitis, alcoholic etiology and decreased body mass index (BMI) were associated with high SWV. CONCLUSIONS: ARFI elastography of the pancreas showed high elasticity in chronic pancreatitis compared to findings in the normal pancreas. This modality is feasible to use for the diagnosis of chronic pancreatitis. PMID- 22065163 TI - Performance of peripheral (serum and molecular) blood markers for diagnosis of endometriosis. AB - PURPOSE: To quantify the mRNA levels of MMP-3, MMP-9, VEGF and Survivin in peripheral blood and the serum levels of CA-125 and Ca19-9 in women with and without endometriosis and to investigate the performance of these markers to differentiate between deep and ovarian endometriosis. METHODS: A case control study enrolled a series of 60 patients. Twenty controls have been matched with 20 cases of ovarian and 20 cases of deep endometriosis. Univariable and multivariable performance of serum CA125 and CA19-9, mRNA for Survivin, MMP9, MMP3 and VEGF genes have been evaluated by means of ROC curves and logistic regression, respectively. RESULTS: No difference in markers' concentration was detected between ovarian and deep endometriosis. In comparison with controls, serum CA125 and CA19 yielded the better sensitivity followed by mRNA for Survivin gene (81.5, 51.9 and 7.5% at 10% false positive rate, respectively). Multivariable estimated odds of endometriosis yielded a sensitivity of 87% at the same false positive rate. CONCLUSIONS: A combination of serum and molecular markers could allow a better diagnosis of endometriosis. PMID- 22065164 TI - Mixed epidermal cyst and mucinous cystadenoma of the ovary: a hitherto unreported entity. PMID- 22065165 TI - A priori assumptions about characters as a cause of incongruence between molecular and morphological hypotheses of primate interrelationships. AB - When molecules and morphology produce incongruent hypotheses of primate interrelationships, the data are typically viewed as incompatible, and molecular hypotheses are often considered to be better indicators of phylogenetic history. However, it has been demonstrated that the choice of which taxa to include in cladistic analysis as well as assumptions about character weighting, character state transformation order, and outgroup choice all influence hypotheses of relationships and may positively influence tree topology, so that relationships between extant taxa are consistent with those found using molecular data. Thus, the source of incongruence between morphological and molecular trees may lie not in the morphological data themselves but in assumptions surrounding the ways characters evolve and their impact on cladistic analysis. In this study, we investigate the role that assumptions about character polarity and transformation order play in creating incongruence between primate phylogenies based on morphological data and those supported by multiple lines of molecular data. By releasing constraints imposed on published morphological analyses of primates from disparate clades and subjecting those data to parsimony analysis, we test the hypothesis that incongruence between morphology and molecules results from inherent flaws in morphological data. To quantify the difference between incongruent trees, we introduce a new method called branch slide distance (BSD). BSD mitigates many of the limitations attributed to other tree comparison methods, thus allowing for a more accurate measure of topological similarity. We find that releasing a priori constraints on character behavior often produces trees that are consistent with molecular trees. Case studies are presented that illustrate how congruence between molecules and unconstrained morphological data may provide insight into issues of polarity, transformation order, homology, and homoplasy. PMID- 22065166 TI - Pedicle subtraction osteotomy through pseudarthrosis to correct thoracolumbar kyphotic deformity in advanced ankylosing spondylitis. AB - INTRODUCTION: Surgical treatment is mandatory for spinal pseudarthrosis in advanced ankylosing spondylitis (AS) patients with painful sagittal deformity and/or neurological deficits. However, the most effective and safe surgical procedure for AS-related symptomatic thoracolumbar pseudarthrosis is still controversial. The purpose of this study is to explore the outcomes of pedicle subtraction osteotomy (PSO) at the level of pseudarthrotic lesion combined with supplemental anterior fusion for patients suffering from kyphotic pseudarthrosis in AS. MATERIALS AND METHODS: Seven AS patients with thoracolumbar pseudarthrosis and kyphotic deformity were reviewed. There were 6 males and 1 female with a mean age of 41.7 years. All patients had back pain. Imaging findings demonstrated 3 column extensive discovertebral destruction in all patients. The preoperative global kyphosis averaged 75 degrees (range, 37 degrees -114 degrees ) with the apex at the level of pseudarthrosis. Three patients had incomplete neurological deficits (Frankel D) preoperatively. All patients underwent PSO at the level of pseudarthrosis in the first stage followed by supplemental anterior fusion in the second stage. Radiographic and clinical outcomes were assessed with an average follow-up of 38 months (range, 24-59 months). The visual analogue scale (VAS) was compared before surgery and at the final follow-up. RESULTS: All patients showed significant pain relief postoperatively and were satisfied with the kyphosis correction as well. Solid bony fusion was shown at the final follow-up. Three patients with neurological deficits had complete recovery of neurological function. The global kyphosis was corrected from 75o to 30o, with a mean correction of 45o. The VAS showed significant improvement. No surgical complication was observed. CONCLUSION: PSO can be safely performed through the site of pseudarthrotic lesion in AS patients with pseudarthrosis and kyphotic deformity. After PSO, supplemental anterior fusion is sometimes necessary to support the anterior and middle column in a second stage if there is a bone defect in the osteotomy site. PMID- 22065167 TI - Use of the iPhone for Cobb angle measurement in scoliosis. AB - PURPOSE: The Cobb technique is the universally accepted method for measuring the severity of spinal deformities. Traditionally, Cobb angles have been measured using protractor and pencil on hardcopy radiographic films. The new generation of mobile 'smartphones' make accurate angle measurement possible using an integrated accelerometer, providing a potentially useful clinical tool for assessing Cobb angles. The purpose of this study was to compare Cobb angle measurements performed using a smartphone and traditional protractor in a series of 20 adolescent idiopathic scoliosis patients. METHODS: Seven observers measured major Cobb angles on 20 pre-operative postero-anterior radiographs of Adolescent Idiopathic Scoliosis patients with both a standard protractor and using an Apple iPhone. Five of the observers repeated the measurements at least a week after the original measurements. RESULTS: The mean absolute difference between pairs of smartphone/protractor measurements was 2.1 degrees , with a small (1 degrees ) bias toward lower Cobb angles with the iPhone. 95% confidence intervals for intra observer variability were +/-3.3 degrees for the protractor and +/-3.9 degrees for the iPhone. 95% confidence intervals for inter-observer variability were +/ 8.3 degrees for the iPhone and +/-7.1 degrees for the protractor. Both of these confidence intervals were within the range of previously published Cobb measurement studies. CONCLUSIONS: We conclude that the iPhone is an equivalent Cobb measurement tool to the manual protractor, and measurement times are about 15% less. The widespread availability of inclinometer-equipped mobile phones and the ability to store measurements in later versions of the angle measurement software may make these new technologies attractive for clinical measurement applications. PMID- 22065168 TI - Efficacy of exercise therapy for the treatment of adolescent idiopathic scoliosis: a review of the literature. AB - PURPOSE: Current evidence regarding the use of exercise therapy in the treatment of adolescent idiopathic scoliosis (AIS) was assessed with a review of published literature. METHODS: An extensive literature search was carried out with commonly used medical databases. A total of 155 papers were identified out of which only 12 papers were deemed to be relevant. RESULTS: There were nine prospective cohort studies, two retrospective studies and one case series. All studies endorsed the role of exercise therapy in AIS but several shortcomings were identified--lack of clarity of patient recruitment and in the method of assessment of curve magnitude, poor record of compliance, and lack of outcome scores. Many studies reported "significant" changes in the Cobb angle after treatment, which were actually of small magnitude and did not take into account the reported inter or intra-observer error rate. All studies had poor statistical analysis and did not report whether the small improvements noted were maintained in the long term. CONCLUSIONS: This unbiased literature review has revealed poor quality evidence supporting the use of exercise therapy in the treatment of AIS. Well-designed randomised controlled studies are required to assess the role of exercise therapy in AIS. PMID- 22065170 TI - A randomized clinical trial of autologous T-cell therapy in multiple sclerosis: subset analysis and implications for trial design. AB - BACKGROUND: Tovaxin is an autologous T-cell immunotherapy under investigation for the treatment of MS. The product consists of in vitro expanded myelin-reactive T cells manufactured against up to six immunodominant peptides derived from three myelin antigens. METHODS: A Phase 2b placebo controlled study (TERMS) was conducted in 150 subjects to gather safety and efficacy data in relapsing remitting MS and clinically isolated syndrome subjects. RESULTS: Tovaxin had a favorable safety profile. Although no statistically significant clinical or radiological benefit of Tovaxin immunotherapy was identified in the modified intent-to-treat population, a prospective analysis of subjects with more active disease favored Tovaxin in terms of annualized relapse rate (ARR) and disability progression. An analysis also found a possible legacy effect of prior disease modifying treatment (DMT) which may have contributed to a lowered ARR in the placebo group. DMT-naive subjects treated with Tovaxin had a lower ARR compared to the placebo group, particularly in those with active baseline disease (ARR >= 1, ARR>1). However, clinical benefit was not was accompanied by a treatment dependent improvement in MRI measures. CONCLUSIONS: Previous DMT exposure may reduce effect size and study power. Limiting subject selection to DMT-treatment naive individuals may be a reasonable approach to phase 2 or proof-of-concept studies of limited duration. PMID- 22065171 TI - Retraction note to: Functionalization of titanium based metallic biomaterials for implant applications. PMID- 22065172 TI - N-(2,4-Dichloro-phen-yl)-4-methyl-benzene-sulfonamide. AB - The mol-ecule of the title compound, C(13)H(11)Cl(2)NO(2)S, is bent at the S atom with a C-SO(2)-NH-C torsion angle of -69.07 (16) degrees . The sulfonyl and aniline rings are rotated relative to each other by 53.0 (1) degrees . In the crystal, pairs of N-H?O(S) hydrogen bonds link the mol-ecules into centrosymmetric dimers. PMID- 22065173 TI - Endonasal endoscopic dacryocystorhinostomy: how to achieve optimal results with simple punch technique. AB - Endonasal endoscopic dacryocystorhinostomy (EEDCR) has been popularized as a minimally invasive technique. Although preliminary reports revealed less success in comparison with external approaches, recent endonasal endoscopic surgeries on various types of DCR have preserved advantages of this technique while diminishing the failures. We described our experience on EEDCR, including the main advantages and disadvantages of it. Hundred consecutive cases of lachrymal problems underwent EEDCR utilizing simple punch removal of bone, instead of powered instrumentation or lasers. The medial aspect of the sac was removed in all of patients, while preserving normal mucosa around the sac. Hundred cases of EEDCR were performed on 81 patients, with 19 bilateral procedures. Nine procedures were performed under local anesthesia. Based on a mean 14 months follow-up, 95 cases were free of symptoms, revealing 95% success rate. The punch technique diminishes the expenses of powered or laser instrumentation with comparable results. It seems that preserving normal tissues and creating a patent rhinostomy with least surgical trauma and less subsequent scar, plays the most important role in achieving desirable results. PMID- 22065174 TI - Spatio-temporal trends of Iberian wild boar contact with Mycobacterium tuberculosis complex detected by ELISA. AB - The continuing expansion of Eurasian wild boar (Sus scrofa) populations raises concerns regarding disease transmission. In south-central Spain, overabundant wild boar are reservoirs of Mycobacterium bovis, and related members of the Mycobacterium tuberculosis complex (MTBC), the causative agents of bovine tuberculosis (bTB). An indirect enzyme-linked immunosorbent assay using bovine purified protein derivative was applied to determine the spatial and temporal distribution of wild boar contact with MTBC in the Iberian Peninsula and to model and identify the associated risk factors. Wild boar apparent seroprevalence was 22%. Seropositives were detected in 71% of 81 sites, including 23 sites where wildlife was thought to be bTB free. The results described a new geographic range of wild boar contact with MTBC and a stable prevalence in this wildlife reservoir that contrasts with the success of bTB control in cattle. Inference of which host (wild boar or cattle) is driving bTB maintenance was not possible with our correlational results. The possibility of a wild boar bTB emergence in non endemic regions should urgently be taken into account to avoid a future scenario resembling the current situation in south-central Spain. PMID- 22065175 TI - Synthesis of novel Eu(III) luminescent probe based on 9- acridinecarboxylic acid skelton for sensing of ds-DNA. AB - Eu(III)-9-acridinecarboxylate (9-ACA) complex was synthesized and characterized by elemental analysis, conductivity measurement, IR spectroscopy, thermal analysis, mass spectroscopy, (1)H-NMR, fluorescence and ultraviolet spectra. The results indicated that the composition of this complex is [Eu(III)-(9 ACA)(2)(NCS)(C(2)H(5)OH)(2)] 2.5 H(2)O and the oxygen of the carbonyl group coordinated to Eu(III). The interaction between the complex with nucleotides guanosine 5'- monophosphate (5'-GMP), adenosine 5'-diphosphates (5'-ADP), inosine (5'-IMP) and CT-DNA was studied by fluorescence spectroscopy. The fluorescence intensity of Eu(III)-9-acridinecarboxylate complex was enhanced with the addition of CT-DNA. The effect of pH values on the fluorescence intensity of Eu(III) complex was investigated. Under experimental conditions, the linear range was 9 50 ng mL(-1) for calf thymus DNA (CT- DNA) and the corresponding detection limit was 5 ng mL(-1). The results showed that Eu(III)-(9-ACA)(2) complex binds to CT DNA with stability constant of 2.41 * 10(4) M. PMID- 22065176 TI - Exploring the structure of psychopathological symptoms: a re-analysis of AMDP data by robust nonmetric multidimensional scaling. AB - This paper investigates the structure of psychopathological symptoms. Based on AMDP symptom profiles, a symptom space was calculated by robust nonmetric multidimensional scaling (NMDS) and the symptom structures of a sample dating from 1980 and a sample from 2002/2003 were compared. The method of NMDS presented in this study allows results from other studies to be confirmed and complemented. The symptom factors identified in the past by factor-analytic studies were replicated as clusters in two-dimensional symptom maps. Additionally, some theoretically assumed clusters of symptoms were detected that were not found in previous factor analysis approaches. From the results, which are depicted in a continuous space, new insights can be gained, especially with regard to questions of categorical and dimensional classifications. The comparison of the structural aspects of the symptomatology across more than two decades resulted in only small divergences and allows conclusions to be drawn about the stability of these structures and consequently of the symptom clusters and dimensions. PMID- 22065177 TI - The neurological manifestations of trauma: lessons from World War I. AB - Changes in the clinical presentation of functional disorders and the influence of social and cultural factors can be investigated through the historical case notes from mental hospitals. World War I (WWI) was a potent trigger of functional disorders with neurological or psychiatric symptoms. We analysed 100 randomly selected case files of German servicemen admitted to the Department of Psychiatry of the Charite Medical School of Berlin University during WWI and classified them according to contemporaneous and retrospective modern diagnoses. We compared the clinical presentations with accounts in the German and British medical literature of the time. Most patients obtained the contemporaneous diagnosis of 'psychopathic constitution' or hysteria reflecting the general view of German psychiatrists that not the war but an individual predisposition was the basis for the development of symptoms. The clinical picture was dominated by pseudoneurological motor or sensory symptoms as well as pseudoseizures. Some soldiers relived combat experiences in dream-like dissociative states that partly resemble modern-day post-traumatic stress disorder. Most servicemen were classified as unfit for military service but very few of them were granted compensation. Severe functional disorders of a neurological character could develop even without traumatic exposure in combat, which is of interest for the current debate on triggers of stress disorders. The high incidence of pseudoseizures accords with the psychiatric literature of the time and contrasts with accounts of war-related disorders in Britain. The tendency of German psychiatrists not to send traumatised servicemen back to active duty also distinguished between German and British practice. Our data contribute to the debate on the changing patterns of human responses to traumatic experience and their historical and social context. PMID- 22065178 TI - The childhood obesity epidemic: lessons for preventing socially determined health conditions. PMID- 22065179 TI - Effects of moral outrage on child welfare reform. PMID- 22065180 TI - Crossing growth percentiles in infancy and risk of obesity in childhood. AB - OBJECTIVE: To examine the associations of upward crossing of major percentiles in weight-for-length in the first 24 months of life with the prevalence of obesity at ages 5 and 10 years. DESIGN: Longitudinal study. SETTING: Multisite clinical practice. PARTICIPANTS: We included 44 622 children aged from 1 month to less than 11 years with 122 214 length/height and weight measurements from January 1, 1980, through December 31, 2008. MAIN EXPOSURE: The number of major weight-for length percentiles crossed during each of four 6-month intervals, that is, 1 to 6 months, 6 to 12 months, 12 to 18 months, and 18 to 24 months. MAIN OUTCOME MEASURES: Odds and observed prevalence of obesity (body mass index [calculated as weight in kilograms divided by height in meters squared] >=95th percentile) at ages 5 and 10 years. RESULTS: Crossing upwards 2 or more weight-for-length percentiles was common in the first 6 months of life (43%) and less common during later age intervals. Crossing upwards 2 or more weight-for-length percentiles in the first 24 months was associated with elevated odds of obesity at ages 5 years (odds ratio, 2.08; 95% CI, 1.84-2.34) and 10 years (1.75; 1.53-2.00) compared with crossing less than 2 major percentiles. Obesity prevalence at ages 5 and 10 was highest among children who crossed upwards 2 or more weight-for-length percentiles in the first 6 months of life. CONCLUSIONS: Crossing upwards 2 or more major weight-for-length percentiles in the first 24 months of life is associated with later obesity. Upward crossing of 2 weight-for-length percentiles in the first 6 months is associated with the highest prevalence of obesity 5 and 10 years later. Efforts to curb excess weight gain in infancy may be useful in preventing later obesity. PMID- 22065181 TI - Physicians' shared decision-making behaviors in attention-deficit/hyperactivity disorder care. AB - OBJECTIVES: To describe the amount of shared decision-making (SDM) behavior exhibited during treatment-planning encounters for children newly diagnosed as having attention-deficit/hyperactivity disorder and to explore relationships between participant characteristics and the amount of SDM. DESIGN: Prospective cohort study. SETTING: Seven community-based primary care pediatric practices in the Cincinnati, Ohio; northern Kentucky; and southeast Indiana regions from October 5, 2009, through August 9, 2010. PARTICIPANTS: Ten pediatricians and 26 families with a 6- to 10-year-old child newly diagnosed as having attention deficit/hyperactivity disorder. OUTCOME MEASURE: The amount of SDM behavior exhibited during videorecorded encounters, as coded by 2 independent raters using the validated Observing Patient Involvement (OPTION) scale, which was adapted for use in pediatric settings and produces a score ranging from 0 (no parental involvement) to 100 (maximal parental involvement). RESULTS: Treatment decisions focused on initiation of medication treatment. The mean (SD) total OPTION score was 28.5 (11.7). More SDM was observed during encounters involving families with white vs nonwhite children (adjusted mean difference score, 14.9; 95% confidence interval [CI], 10.2-19.6; P < .001), private vs public health insurance coverage (adjusted mean difference score, 15.1; 11.2-19.0; P < .001), mothers with at least some college education vs high school graduate or less (adjusted mean difference score, 12.3; 7.2-17.4; P < .001), and parents who did not screen positive for serious mental illness vs those who did (adjusted mean difference score, 15.0; 11.9-18.1; P < .001). CONCLUSIONS: Low levels of SDM were observed. Exploratory analyses identified potential disparities and barriers. Interventions may be needed to foster SDM with all parents, especially those of nonwhite race, of lower socioeconomic status, of lower educational level, and with serious mental illness. PMID- 22065182 TI - A national profile of caregiver challenges among more medically complex children with special health care needs. AB - OBJECTIVES: To profile the national prevalence of more medically complex children with special health care needs (CSHCN) and the diversity of caregiver challenges that their families confront. DESIGN: Secondary analysis of the 2005-2006 National Survey of Children With Special Health Care Needs (unweighted n = 40 723). SETTING: United States-based population. PARTICIPANTS: National sample of CSHCN. MAIN EXPOSURE: More complex CSHCN were defined by incorporating components of child health and family need, including medical technology dependence and care by 2 or more subspecialists. MAIN OUTCOME MEASURES: Caregiver challenges were defined by family-reported care burden (including hours providing care coordination and home care), medical care use (on the basis of health care encounters in the last 12 months), and unmet needs (defined by 15 individual medical care needs and a single nonmedical service need). RESULTS: Among CSHCN, 3.2% (weighted n = 324 323) met criteria for more complex children, representing 0.4% of all children in the United States. Caregivers of more complex CSHCN reported a median of 2 (interquartile range, 1-6) hours per week on care coordination and 11 to 20 (interquartile range, 3->21) hours per week on direct home care. More than half (56.8%) reported financial problems, 54.1% reported that a family member stopped working because of the child's health, 48.8% reported at least 1 unmet medical service need, and 33.1% reported difficulty in accessing nonmedical services. CONCLUSIONS: Extraordinary and diverse needs are common among family caregivers of more complex CSHCN. Enhanced care coordination support, respite care, and direct home care may begin to address the substantial economic burden and the multiple unmet needs that many of these families face. PMID- 22065183 TI - Impact of a more restrictive approach to urinary tract imaging after febrile urinary tract infection. AB - OBJECTIVES: To determine the impact of using an algorithm requiring selective rather than routine urinary tract imaging following a first febrile urinary tract infection (UTI) on imaging use, detection of vesicoureteral reflux (VUR), prophylactic antibiotic use, and UTI recurrence within 6 months. DESIGN: Retrospective review comparing outcomes during periods before algorithm use (September 1, 2006, to August 31, 2007) and after algorithm use (September 1, 2008, to August 31, 2009). The new algorithm, which adapted recommendations from the United Kingdom's National Institute for Health and Clinical Excellence 2007 guidelines, was implemented in 2008. The algorithm calls for renal ultrasonography in most cases and restricts voiding cystourethrography for use in patients with certain risk factors. SETTING: County health system. PARTICIPANTS: Children younger than 2 years with a first febrile UTI. INTERVENTION: Selective algorithm for urinary tract imaging. MAIN OUTCOME MEASURES: Urinary tract imaging use, detection of VUR, prophylactic antibiotic use, and UTI recurrence within 6 months. RESULTS: After introduction of the new algorithm, voiding cystourethrography and prophylactic antibiotic use decreased markedly. Rates of UTI recurrence within 6 months and detection of grades 4 and 5 VUR did not change, but detection of grades 1 to 3 VUR decreased substantially. Patients in the prealgorithm group with grades 1 to 3 VUR who would have been missed with selective screening underwent no interventions other than successive urinary tract imaging and prophylactic antibiotic use. CONCLUSIONS: By restricting urinary tract imaging after an initial febrile UTI, rates of voiding cystourethrography and prophylactic antibiotic use decreased substantially without increasing the risk of UTI recurrence within 6 months and without an apparent decrease in detection of high-grade VUR. Clinicians can be more judicious in their use of urinary tract imaging. PMID- 22065184 TI - Effect of neuromuscular warm-up on injuries in female soccer and basketball athletes in urban public high schools: cluster randomized controlled trial. AB - OBJECTIVE: To determine the effectiveness of coach-led neuromuscular warm-up on reducing lower extremity (LE) injuries in female athletes in a mixed-ethnicity, predominantly low-income, urban population. DESIGN: Cluster randomized controlled trial. SETTING: Chicago public high schools. PARTICIPANTS: Of 258 coaches invited to participate, 95 (36.8%) enrolled (1558 athletes). Ninety coaches and 1492 athletes completed the study. INTERVENTIONS: We randomized schools to intervention and control groups. We trained intervention coaches to implement a 20-minute neuromuscular warm-up. Control coaches used their usual warm-up. MAIN OUTCOME MEASURES: Coach compliance was tracked by self-report and direct observation. Coaches reported weekly athlete exposures (AEs) and LE injuries causing a missed practice or game. Research assistants interviewed injured athletes. Injury rates were compared between the control and intervention groups using chi(2) and Fisher exact tests. Significance was set at P < .05. Poisson regression analysis adjusted for clustering and covariates in an athlete subset reporting personal information (n = 855; 57.3%). RESULTS: There were 28 023 intervention AEs and 22 925 control AEs. Intervention coaches used prescribed warm-up in 1425 of 1773 practices (80.4%). Intervention athletes had lower rates per 1000 AEs of gradual-onset LE injuries (0.43 vs 1.22, P < .01), acute-onset noncontact LE injuries (0.71 vs 1.61, P < .01), noncontact ankle sprains (0.25 vs 0.74, P = .01), and LE injuries treated surgically (0 vs 0.17, P = .04). Regression analysis showed significant incidence rate ratios for acute-onset noncontact LE injuries (0.33; 95% CI, 0.17-0.61), noncontact ankle sprains (0.38; 95% CI, 0.15-0.98), noncontact knee sprains (0.30; 95% CI, 0.10-0.86), and noncontact anterior cruciate ligament injuries (0.20; 95% CI, 0.04-0.95). CONCLUSION: Coach-led neuromuscular warm-up reduces noncontact LE injuries in female high school soccer and basketball athletes from a mixed-ethnicity, predominantly low-income, urban population. TRIAL REGISTRATION CLINICALTRIALS.ORG IDENTIFIER: NCT01092286. PMID- 22065185 TI - Picture of the month--quiz case. Juvenile dermatomyositis. PMID- 22065186 TI - Early identification of children at risk of developing obesity. PMID- 22065187 TI - Reduced imaging after urinary tract infection: are benefits accompanied by adverse risks? PMID- 22065188 TI - Translating cost-effective injury prevention research into sustainable change on the playing field: the youth injury epidemic. PMID- 22065189 TI - National school lunch program for all. PMID- 22065190 TI - Reducing screen time for children. PMID- 22065191 TI - Robot-assisted transaxillary thyroid surgery in the United States: is it comparable to open thyroid lobectomy? AB - BACKGROUND: The purpose of this study was to compare the outcome of robot assisted transaxillary thyroid surgery (RATS) to the standard open technique for thyroid lobectomy in the U.S. population. METHODS: Comparison was made between 25 consecutive patients who underwent thyroid lobectomy via RATS and 25 patients who underwent open thyroid lobectomy. All patients met predetermined criteria for RATS. Clinical characteristics of patients and operative data were compared between groups using the Fisher exact or the Kruskal-Wallis test. RESULTS: The RATS and open groups were similar in gender (92% vs 84% female), median body mass index (BMI) (25 vs 26), preoperative cytology (P=.71), and postoperative diagnosis (P=.91). Operative time for the RATS group was longer than the open group [median 121 minutes (range 74-199 minutes) vs 68 minutes (41-112 minutes), P<.0001]. Estimated blood loss was greater in the RATS group [median 10 cc (0-150 cc) vs 0 cc (0-25 cc), P=.0042]. Unlike the open group, postoperative complications in the RATS group included 2 patients with neurological deficits in the brachial plexus distribution. The postoperative incidence of temporary hoarseness, bleeding, infection, seroma, numbness, and length of hospital stay did not differ significantly between groups. CONCLUSIONS: In a select group of patients, RATS is comparable to open thyroid lobectomy in terms of postoperative complications and hospital stay. Patients should be counseled that RATS is associated with a longer operative time, a potential for brachial plexus neurological deficits, and larger (although still low) blood loss. A prospective trial further evaluating cost, quality of life, and patient-reported satisfaction is warranted. PMID- 22065192 TI - Patterns of care, prognosis, and survival in patients with metastatic gastrointestinal stromal tumors (GIST) refractory to first-line imatinib and second-line sunitinib. AB - BACKGROUND: Data regarding the management and outcome of patients with metastatic gastrointestinal stromal tumors (GIST) refractory to 1st-line imatinib and 2nd line sunitinib are limited. METHODS: Medical records of 223 imatinib-resistant and sunitinib-resistant GIST who were treated in 11 major referral centers were reviewed. RESULTS: The three most frequent drugs used in the 3rd-line setting were: nilotinib n = 67 (29.5%), sorafenib n = 55 (24.5%), and imatinib n = 40 (17.5%). There were 18 patients (8%) who received best supportive care (BSC) only. The median progression-free survival (PFS) and overall survival (OS) on 3rd line treatment were 3.6 months [95% confidence interval (95% CI), 3.1-4.1] and 9.2 months (95% CI, 7.5-10.9), respectively. Multivariate analysis showed that, in the 3rd-line setting, albumin level and KIT/PDGFRA mutational status were significantly associated with PFS, whereas performance status and albumin level were associated with OS. After adjustment for prognostic factors, nilotinib and sorafenib provided the best PFS and OS. Rechallenge with imatinib was also associated with improved OS in comparison with BSC. CONCLUSION: In the 3rd-line setting, rechallenge with imatinib provided limited clinical benefit but was superior to BSC. Sorafenib and nilotinib have significant clinical activity in imatinib-resistant and sunitinib-resistant GIST and may represent an alternative for rechallenge with imatinib. PMID- 22065193 TI - Molecular detection of sentinel node micrometastases in patients with clinical N0 gastric carcinoma with real-time multiplex reverse transcription-polymerase chain reaction assay. AB - PURPOSE: Described is a novel real-time multiplex reverse transcription polymerase chain reaction (RT-PCR) assay suitable for intraoperative detection of micrometastasis (MM) in sentinel nodes (SNs) dissected from patients with clinical N0 (cN0) gastric carcinoma. METHODS: One hundred three patients with gastric cancer, who were preoperatively diagnosed with cN0 and clinical T1 or T2, were enrolled. The patients underwent SN mapping followed by standard radical gastrectomy with lymph node dissection. In addition to all SNs, non-SNs (NSNs) within the SN lymphatic basin and NSN from a different lymphatic basin were randomly sampled. All SNs and NSNs were examined by routine histologic diagnosis and RT-PCR for the expression of cytokeratin (CK) 19, CK20, and carcinoembryonic antigen (CEA). RESULTS: The RT-PCR assay and histologic examination were performed in 512 SNs and 299 NSNs from 103 patients. Pathologic l lymph node metastasis was revealed in 13 (12.6%) of 103 patients. All metastatic lymph nodes were identified within SNs. SNs of these 13 patients had positive findings on RT PCR. Twenty-eight (27.2%) of 103 patients had negative histopathology but positive findings on RT-PCR. In 7 patients (6.8%), SNs were negative but NSNs were positive on RT-PCR. RT-PCR-positive NSNs were present in the same station as corresponding SNs in 3 of these 7 patients and in the same basin as SNs in 4 patients. CONCLUSIONS: The real-time multiplex RT-PCR assay is a useful tool for the detection of MM in SNs and NSNs in patients with gastric cancer. PMID- 22065194 TI - Adverse effects of smoking on postoperative outcomes in cancer patients. AB - BACKGROUND: The possible negative effects of smoking on postoperative outcomes have not been well studied in cancer patients. METHODS: We used the VA Surgical Quality Improvement Program (VASQIP) database for the years 2002-2008, which assesses preoperative risk factors and postoperative outcomes for patients undergoing major surgery within the VA healthcare system. RESULTS: Compared with never smokers, prior smokers and current smokers with GI malignancies were significantly more likely to have surgical site infection (SSI) (odds ratio [OR], 1.25; 95% confidence interval [95% CI], 1.09-1.44) (OR, 1.20; 95% CI, 1.05-1.38), combined pulmonary complications (combined pulmonary outcome [CPO]: pneumonia, failure to wean from ventilator, reintubation) (OR, 1.60; 95% CI, 1.38-1.87) (OR, 1.96; 95% CI, 1.68-2.29), and return to the operating room (OR, 1.20; 95% CI, 1.03-1.39) (OR, 1.31; 95% CI, 1.13-1.53), respectively. Both prior and current smokers had a significantly higher mortality at 30 days (OR, 1.50; 95% CI, 1.19 1.89) (OR, 1.41; 95% CI, 1.08-1.82) and 1 year (OR, 1.22; 95% CI, 1.08-1.38) (OR, 1.62; 95% CI, 1.43-1.85). Thoracic surgery patients who were current smokers were more likely to develop CPO (OR, 1.62; 95% CI, 1.25-2.11) and mortality within 1 year (OR, 1.50; 95% CI, 1.17-1.92) compared with nonsmokers, but SSI rates were not affected by smoking status. Current smokers had a significant increase in postsurgical length of stay (overall 4.3% [P < .001], GI 4.7% [P = .003], thoracic 9.0% [P < .001]) compared with prior smokers. CONCLUSIONS: Prior and current smoking status is a significant risk factor for major postoperative complications and mortality following GI cancer and thoracic operations in veterans. Smoking cessation should be encouraged prior to all major cancer surgery in the VA population to decrease postoperative complications and length of stay. PMID- 22065195 TI - Aggressive variants of papillary thyroid cancer: incidence, characteristics and predictors of survival among 43,738 patients. AB - BACKGROUND: The diffuse sclerosing (DSV) and tall cell (TCV) variants are considered aggressive subtypes of papillary thyroid cancer (PTC) for which data are limited. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1988-2008) was used to compare the incidence and clinical/pathologic characteristics of DSV and TCV with classic PTC. Prognostic factors associated with survival were analyzed by chi-square test, analysis of variance, log rank test, and Cox multivariate regression. RESULTS: There were 261 DSV, 573 TCV, and 42,904 PTC patients. Compared to a 60.8% increase in classic PTC incidence, DSV and TCV incidence increased by 126% (P (trend) = 0.052) and 158% (P (trend) = 0.002), respectively. Aggressive variants were associated with higher rates of extrathyroidal extension, multifocality, and nodal and distant metastasis (all P < 0.001) compared to classic PTC. Nodal metastasis was more likely with DSV (72.2% vs. 66.8% TCV vs. 56.3% PTC, P < 0.001); distant metastasis was most common with TCV (11.1% vs. 7.3% DSV vs. 4.3% PTC, P < 0.001). After adjustment, DSV [hazard ratio (HR) 1.8, P = 0.007] and TCV (HR 1.9, P < 0.001) histologies were associated with significantly reduced survival (5-year overall: 87.5% DSV, 80.6% TCV vs. 93.5% PTC, P < 0.001). Tumor size independently predicted worse prognosis for TCV (HR 1.29, P < 0.001) but not DSV patients. Thyroid surgery and radioiodine improved survival of DSV and TCV patients (all P < 0.05). Patients with aggressive variants who received external-beam radiotherapy did not experience improved survival. CONCLUSIONS: DSV and TCV are rare, increasing in incidence, and have a worse prognosis than classic PTC. Patients with these variants should be treated aggressively with thyroidectomy and radioiodine, regardless of tumor size. PMID- 22065196 TI - catena-Poly[[bis-(3-methyl-benzoato-kappaO,O')lead(II)]-MU-4,4'-bipyridine kappaN:N']. AB - In the title complex, [Pb(C(8)H(7)O(2))(2)(C(10)H(8)N(2))](n), the Pb(II) atom is located on a twofold rotation axis and is six-coordinated by four carboxyl-ate O atoms from two 3-methyl-benzoate ligands and two N atoms from two 4,4'-bipyridine (4,4'-bpy) ligands, displaying a hemi-directed coordination. The 4,4'-bpy ligand has an inversion center at the mid-point of the central C-C bond. The Pb(II) atoms are linked by bidentate bridging 4,4'-bpy into a chain along [101]. These chains are further connected into layers via C-H?O hydrogen bonds. PMID- 22065197 TI - Endovascular treatment of two concomitant causes of pulsatile tinnitus: sigmoid sinus stenosis and ipsilateral jugular bulb diverticulum. Case report and literature review. AB - We describe a rare case of highly invalidating pulsatile tinnitus associated with both stenosis of the sigmoid sinus and ipsilateral jugular bulb diverticulum. Both conditions were successfully treated by positioning a stent across the sigmoid sinus and jugular bulb. To our knowledge, the present clinical case represents the first report of such an approach. The therapeutic decision-making is discussed in relation to the etiopathologic hypothesis put forward. PMID- 22065198 TI - Gemcitabine-induced posterior reversible encephalopathy syndrome: a case report. AB - Gemcitabine is a commonly used chemotherapeutic agent for a variety of tumors. Although this nucleoside analog antineoplastic agent is similar in structure to cytarabine, central nervous system toxicities have rarely been attributed to gemcitabine. The posterior reversible encephalopathy syndrome (PRES) is a condition characterized by reversible neurological and radiological findings that has been associated with use of chemotherapeutic and more recently novel targeted therapies. We describe one case of a 41-year-old woman with PRES under treatment for leiomyosarcoma because of the probable association with gemcitabine. Our case, to our knowledge, represents the seventh published report of this particular toxicity. Naranjo algorithm, efficacious method for assessing the causality of adverse drug reactions (ADRs) from a case report, suggests a direct casual relationship. PRES is probably a rare complication of gemcitabine, but the oncologist should take it into careful consideration, because PRES is reversible with treatment of current hypertension or removal of the causative agent. However, failure to quickly recognize the syndrome and discontinue the offending agent may result in profound and permanent central nervous system dysfunction or death. PMID- 22065199 TI - Temozolomide plus radiotherapy for glioblastoma in a Canadian province: efficacy versus effectiveness and the impact of O6-methylguanine-DNA-methyltransferase promoter methylation. AB - BACKGROUND: Radiotherapy with concomitant and adjuvant temozolomide has been the standard of care for newly diagnosed glioblastoma in adults since the pivotal trial by Roger Stupp and colleagues. The effectiveness of this regimen has not been evaluated in Canada. Additionally, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation on patient survival has not been confirmed. Hence, survival outcomes and MGMT predictive value were compared for the patients in Alberta versus the Stupp trial population. METHODS: Retrospective chart review of 215 adult glioblastoma patients who started radiotherapy and temozolomide between January 2007 and December 2010 at the Cross Cancer Institute (Edmonton, Alberta) or the Tom Baker Cancer Centre (Calgary, Alberta). RESULTS: In the Alberta population, median overall survival was 14.3 months (vs. 14.6 months in trial, p = NS) and median progression-free survival was 5.8 months (vs. 6.9 months in trial, p = NS). However, unlike the trial, the Alberta MGMT subgroup analysis for overall survival was not statistically significant, despite a hazard ratio of 0.65 in favor of the methylated group. More Alberta patients received corticosteroids (p < 0.0001) and fewer underwent complete resection (p = 0.0001) or a postprogression second surgery (p = 0.01) than the Stupp population, but characteristics were otherwise similar. CONCLUSION: Current practice in Alberta enables patients to achieve overall and progression-free survival similar to the clinical trial. Further follow-up is required to confirm the predictive value of the MGMT assay. Until that is clarified or better treatments are developed, it is reasonable to continue offering this treatment regimen to patients regardless of MGMT methylation status. PMID- 22065200 TI - Twenty years of multidisciplinary research and practice: the Journal of Occupational Rehabilitation then and now. AB - BACKGROUND: Early research of work disability in the 1980s showed a complexity of factors influencing pain and health-related functional limitation at work; hence, multidisciplinary perspectives were necessary to understand the complex interplay between biomechanical, organizational, social, and psychological factors impacting work disability. To address this need, the Journal of Occupational Rehabilitation was founded in 1991 with the goal of providing a scientific, yet practical forum for presenting multidisciplinary research and practice in work disability. Now, the 20-year collection of articles in the Journal reflects important trends and directions in the field of occupational rehabilitation. METHODS: We conducted a retrospective summary of the past 20 years of the Journal of Occupational Rehabilitation, including its inaugural goals and intent, rates of submission and acceptance, trends in the types of articles published, study topics, global distribution of authors, and future directions. RESULTS: The original goal of providing a multidisciplinary scientific and practical forum has been met, but current trends reflect a maturing scientific evidence base, with less representation of employer-based case studies and practical innovations. There has been a dramatic increase in the international representation of studies, authors, and peer reviewers outside of the US. Also, published studies now address work disability for a larger number of health concerns. CONCLUSIONS: Contributions to the Journal continue to reflect a multidisciplinary perspective, but the Journal has seen significant changes with respect to international representation, the expanding study of non-musculoskeletal sources of work disability, and the maturing scientific evidence base in the field of occupational rehabilitation. Future volumes of the Journal will likely reflect continuing changes in the global economy, workforce fitness, and job demands. PMID- 22065201 TI - Organs-on-a-chip: a focus on compartmentalized microdevices. AB - Advances in microengineering technologies have enabled a variety of insights into biomedical sciences that would not have been possible with conventional techniques. Engineering microenvironments that simulate in vivo organ systems may provide critical insight into the cellular basis for pathophysiologies, development, and homeostasis in various organs, while curtailing the high experimental costs and complexities associated with in vivo studies. In this article, we aim to survey recent attempts to extend tissue-engineered platforms toward simulating organ structure and function, and discuss the various approaches and technologies utilized in these systems. We specifically focus on microtechnologies that exploit phenomena associated with compartmentalization to create model culture systems that better represent the in vivo organ microenvironment. PMID- 22065202 TI - Nanomaterial-based biosensor as an emerging tool for biomedical applications. AB - The combination of nanomaterials and biological sensing elements to selectively recognize chemical or biological molecules has resulted in the development of novel nanobiosensors. Nanobiosensors offer several important advantages over conventional biological procedures, and could have a significant impact on humankind. Hence, the momentum toward building miniaturized, reliable, sensitive, and selective sensing instruments has focused on combining nanomaterials with biomolecules for detection of a wide range of analytes. In this article, we present an overview of the various nanomaterial-based biosensors that utilize different biological recognition elements for biomedical applications. In this review, several types of nanomaterial-based biosensors along with their applications are discussed, including the latest developments in the field of nanobiosensors for biomedical applications. PMID- 22065203 TI - Kinematic modeling-based left ventricular diastatic (passive) chamber stiffness determination with in-vivo validation. AB - The slope of the diastatic pressure-volume relationship (D-PVR) defines passive left ventricular (LV) stiffness kappa. Although kappa is a relative measure, cardiac catheterization, which is an absolute measurement method, is used to obtain the former. Echocardiography, including transmitral flow velocity (Doppler E-wave) analysis, is the preferred quantitative diastolic function (DF) assessment method. However, E-wave analysis can provide only relative, rather than absolute pressure information. We hypothesized that physiologic mechanism based modeling of E-waves allows derivation of the D-PVR(E-wave) whose slope, kappa(E-wave), provides E-wave-derived diastatic, passive chamber stiffness. Our kinematic model of filling and Bernoulli's equation were used to derive expressions for diastatic pressure and volume on a beat-by-beat basis, thereby generating D-PVR(E-wave), and kappa(E-wave). For validation, simultaneous (conductance catheter) P-V and echocardiographic E-wave data from 30 subjects (444 total cardiac cycles) having normal LV ejection fraction (LVEF) were analyzed. For each subject (15 beats average) model-predicted kappa(E-wave) was compared to experimentally measured kappa(CATH) via linear regression yielding as follows: kappa(E-wave) = alphakappa(CATH) + b (R(2) = 0.92), where, alpha = 0.995 and b = 0.02. We conclude that echocardiographically determined diastatic passive chamber stiffness, kappa(E-wave), provides an excellent estimate of simultaneous, gold standard (P-V)-defined diastatic stiffness, kappa(CATH). Hence, in chambers at diastasis, passive LV stiffness can be accurately determined by means of suitable analysis of Doppler E-waves (transmitral flow). PMID- 22065204 TI - The Annals of Biomedical Engineering: inception to signature journal. AB - The Annals of Biomedical Engineering, the flagship journal of the Biomedical Engineering Society, developed through four distinct stages. Once an editorial infrastructure was in place and a publisher was secured, a long-lived struggle for sufficient manuscripts and financial stability ensued. The journal achieved a degree of stableness by the mid-1980s. Electronic communication and on-line publishing in the 1990s allowed more rapid turn around but the increased acceptance of quality manuscripts created pressures from insufficient available pages. The journal finally turned to self-publication. The Board of Directors and the Publications Board carefully nurtured the journal over the years with financial support and policy. Still, the bulk of the effort was carried by the editors. They dealt with an ever increasing complex publishing process that now supports three Society journals. PMID- 22065205 TI - Occurrence and distribution of salsolinol-like compound, 1-acetyl-6,7-dihydroxy 1,2,3,4-tetrahydroisoquinoline (ADTIQ) in parkinsonian brains. AB - Parkinson's disease (PD) arises from the loss of dopaminergic neurons in the substantia nigra. 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) is well known to cause Parkinsonism in humans with neurotoxicity specific for dopaminergic neurons. The experience with MPTP supports the hypothesis that endogenous or xenobiotic neurotoxins are involved in the pathogenesis of PD in humans. In our study, 1-acetyl-6, 7-dihydroxy-1, 2, 3, 4-tetrahydro-isoquinoline (ADTIQ), a novel compound, was found in frozen human brain tissues. The formation of ADTIQ was demonstrated using dopamine and methylglyoxal under physiological conditions. Methylglyoxal is a by-product of glycolysis. ADTIQ and its precursors, dopamine and methylglyoxal, were detected in different regions of frozen human brains such as the substantia nigra, caudate nucleus, putamen, frontal cortex, and the cerebellum. A significant difference in ADTIQ levels between control and Parkinson's patients was found; for instance, the ADTIQ level in putamen of PD patients was 0.76 +/- 0.27 nmol/g compared to 0.10 +/- 0.01 nmol/g in control. Our results might indicate that ADTIQ is possibly related to Parkinson's disease. PMID- 22065206 TI - Preparation and properties of nanoscale containers for biomedical application in drug delivery: preliminary studies with kynurenic acid. AB - The main purpose of this study was to facilitate the delivery of kynurenic acid (KYNA) across the blood-brain barrier (BBB) by applying micelles as nanoscale containers. Non-ionic amphiphilic molecules were used for preparation of spherical micelles for delivery of kynurenic acid in aqueous solution in physiological condition. It was established that Triton X 100 and Lutensol AP 20 non-ionic surfactants are able to produce stable nanocontainers for delivery of kynurenic acid molecules. The incorporation of KYNA molecules was investigated by dynamic light scattering and the size of micelles were calculated between 5 and 10 nm in 150 mM NaCl and pH 7.5-7.6 solutions. Encapsulated kynurenic acid showed a significantly higher blood-brain barrier permeability compared with non encapsulated kynurenic acid. The in vivo experiments showed that the encapsulated kynurenic acid is able to display effects within the central nervous system, even after its peripheral administration. PMID- 22065207 TI - Type A monoamine oxidase is associated with induction of neuroprotective Bcl-2 by rasagiline, an inhibitor of type B monoamine oxidase. AB - Rasagiline and (-)deprenyl (selegiline), irreversible type B monoamine oxidase (MAO-B) inhibitors, protect neuronal cells through gene induction of pro-survival Bcl-2 and neurotrophic factors in the cellular models of neurodegenerative disorders. In this paper, the role of MAO in the up-regulation of neuroprotective Bcl-2 gene by these inhibitors was studied using type A MAO (MAO-A) expressing wild SH-SY5Y cells and the transfection-enforced MAO-B overexpressed cells. Rasagiline and (-)deprenyl, and also befloxatone, a reversible MAO-A inhibitor, increased Bcl-2 mRNA and protein in SH-SY5Y cells. Silencing MAO-A expression with short interfering (si) RNA suppressed Bcl-2 induction by rasagiline, but not by (-)deprenyl. MAO-B overexpression inhibited Bcl-2 induction by rasagiline and befloxatone, but did not affect that by (-)deprenyl, suggesting the different mechanisms behind Bcl-2 gene induction by these MAO-B inhibitors. The novel role of MAO-A in Bcl-2 induction by rasagiline is discussed with regard to the molecular mechanism underlying neuroprotection by the MAO inhibitors. PMID- 22065208 TI - Interaction of insulin and PPAR-alpha genes in Alzheimer's disease: the Epistasis Project. AB - Altered glucose metabolism has been described in Alzheimer's disease (AD). We re investigated the interaction of the insulin (INS) and the peroxisome proliferator activated receptor alpha (PPARA) genes in AD risk in the Epistasis Project, including 1,757 AD cases and 6,294 controls. Allele frequencies of both SNPs (PPARA L162V, INS intron 0 A/T) differed between Northern Europeans and Northern Spanish. The PPARA 162LL genotype increased AD risk in Northern Europeans (p = 0.04), but not in Northern Spanish (p = 0.2). There was no association of the INS intron 0 TT genotype with AD. We observed an interaction on AD risk between PPARA 162LL and INS intron 0 TT genotypes in Northern Europeans (Synergy factor 2.5, p = 0.016), but not in Northern Spanish. We suggest that dysregulation of glucose metabolism contributes to the development of AD and might be due in part to genetic variations in INS and PPARA and their interaction especially in Northern Europeans. PMID- 22065209 TI - CSF biomarkers in different phenotypes of Parkinson disease. AB - CSF biomarker studies were performed in 6 patients each with tremor-dominant (TD) and non-tremor-dominant (NT) Parkinson disease (PD) patients, 27 Alzheimer disease (AD) and 17 age-matched controls. In both NT-PD and AD patients total tau levels and the cortex tau/Abeta-42 were significantly increased compared to both TD-PD patients and controls (p < 0.01). These data in a small cohort confirm previous studies, corroborating the opinion that CSF levels of tau protein and the index total-tau/Abeta-42 may be potential markers of the severity of neurodegeneration in PD. PMID- 22065210 TI - Instability of syllable repetition in progressive supranuclear palsy. AB - Dysarthria is a prominent feature of progressive supranuclear palsy (PSP) and consists--amongst other features--of impaired speech fluency. Since in Parkinson's disease (PD) steadiness of syllable repetition in the course of the performance has been shown to be impaired, the aim of the present study was to investigate if measurement of syllable repetition shows similar or even more pronounced abnormalities in PSP. Thirty six patients with the clinical diagnosis of PSP (16 PSP-Richardson syndrome/PSP-RS and 20 PSP-parkinsonism/PSP-P), 60 patients with PD and 32 healthy speakers were tested. Participants had to repeat a single syllable in a self chosen isochronous pace. Percental coefficient of variance (COV) of interval length was measured for description of pace stability throughout the performance. All patients were tested according to Unified Parkinson's Disease Rating Scale (UPDRS III). Patients with PSP were additionally scored according to PSP rating scale (PSPRS). In the PSP group, COV was significantly worse not only when compared with healthy speakers but also when compared with PD patients of similar disease duration and similar global motor impairment. COV showed only a trend to higher values in the subgroup with PSP-RS as compared to PSP-P. In the PSP-P, but not in the PSP-RS subgroup, there was a positive correlation between COV and PSPRS/UPDRS III. PSP patients feature more pronounced difficulties in the steady syllable repetition than patients with PD and healthy controls as a hint for a more profound dysfunction of basal motor speech performance in PSP than in PD. PMID- 22065211 TI - The difficulties of clinical trials evaluating therapeutic agents in patients with severe sepsis. AB - INTRODUCTION: Although the pathophysiology of sepsis has been extensively studied, the disease remains a common cause of death in the critically ill patient. It thus remains one of the most pressing clinical and economic problems of modern medicine. A vast amount of inflammatory mediators have been identified as key factors in driving sepsis. Therapeutic agents designed to target these mediators have so far failed to demonstrate significant clinical benefit. METHODS: Clinical trials are the standard for assessing safety and efficacy of novel agents but are made difficult by the heterogeneous nature of septic patients. This review aims to highlight the complex nature of sepsis and the inherent difficulties encountered in designing clinical trials in these patients. The major factors contributing to the difficulties in improving internal and external validity will be discussed with the aim of guiding future study design. CONCLUSIONS: The design of clinical trials on the septic patient remains a challenge. Methodology must be rigorous if seemingly positive clinical trials which are widely implemented are later discredited as a result of poor study design. Many lessons can be learnt from the study design of the PROWESS trial, however there remains room for improvement. This review serves as a stimulus and guide in motivating much needed high quality clinical trials in sepsis. PMID- 22065212 TI - Beyond AREDS: is there a place for antioxidant therapy in the prevention/treatment of eye disease? AB - Age-related macular degeneration (AMD), the major cause of blindness in adults (65 years of age and older), and diabetic retinopathy, the major cause of blindness in working adults, are chronic, progressive diseases with multifaceted etiologies that are not fully understood. Progression and lack of treatment of both diseases may lead to the advanced stage with neovascularization. Although the detailed cellular mechanisms leading to the development of AMD and diabetic retinopathy remain elusive, oxidative damage to the retina and its pigment epithelium are considered to be involved. Clinical studies have shown that the progression of AMD can be slowed down by nutritional antioxidants, but trials with antioxidants for diabetic retinopathy (very limited in number) have been inconclusive. Long-term administration of the AREDS antioxidants, the same nutritional antioxidants that have been demonstrated to slow the progression of AMD, have yielded exciting results in preventing the pathogenesis of retinopathy in diabetic rodents. These results suggest the merit of testing the AREDS antioxidants in a clinical trial to prevent the development and/or progression of diabetic retinopathy, with the possibility of reducing the impact of this common vision-threatening disease. PMID- 22065213 TI - Are religiosity and spirituality associated with obesity among African Americans in the Southeastern United States (the Jackson Heart Study)? AB - There are several lines of evidence that suggest religiosity and spirituality are protective factors for both physical and mental health, but the association with obesity is less clear. This study examined the associations between dimensions of religiosity and spirituality (religious attendance, daily spirituality, and private prayer), health behaviors and weight among African Americans in central Mississippi. Jackson Heart Study participants with complete data on religious attendance, private prayer, daily spirituality, caloric intake, physical activity, depression, and social support (n = 2,378) were included. Height, weight, and waist circumference were measured. We observed no significant association between religiosity, spirituality, and weight. The relationship between religiosity/spirituality and obesity was not moderated by demographic variables, psychosocial variables, or health behaviors. However, greater religiosity and spirituality were related to lower energy intake, less alcohol use, and less likelihood of lifetime smoking. Although religious participation and spirituality were not cross-sectionally related to weight among African Americans, religiosity and spirituality might promote certain health behaviors. The association between religion and spirituality and weight gain deserves further investigation in studies with a longitudinal study design. PMID- 22065214 TI - Mass spectrometry-based chemoproteomic approaches. AB - The term "chemical proteomics" refers to a research area at the interface of chemistry, biochemistry, and cell biology that focuses on studying the mechanism of action of bioactive small molecule compounds, which comprises the mapping of their target proteins and their impact on protein expression and posttranslational modifications in target cells or tissues of interest on a proteome-wide level. For this purpose, a large arsenal of approaches has emerged in recent years, many of which employing quantitative mass spectrometry. This review briefly summarizes major experiment types employed in current chemical proteomics research. PMID- 22065215 TI - Chemical proteomics in drug discovery. AB - Real-world drug discovery and development remains a notoriously unproductive and increasingly uneconomical process even in the Omics era. The dominating paradigm in the industry continues to be target-based drug design, with an increased perception of the role of signaling pathways in homeostasis and in disease. Since proteins represent the major type of drug targets, proteomics-based approaches, which study proteins under relatively physiological conditions, have great potential if they can be reduced to practice such that they successfully complement the arsenal of drug discovery techniques. This chapter discusses examples of drug discovery processes where chemical proteomics-based assays using native endogenous proteins should have substantial impact. PMID- 22065216 TI - Compound immobilization and drug-affinity chromatography. AB - Bioactive small molecules act through modulating a yet unpredictable number of targets. It is therefore of critical importance to define the cellular target proteins of a compound as an entry point to understanding its mechanism of action. Often, this can be achieved in a direct fashion by chemical proteomics. As with any affinity chromatography, immobilization of the bait to a solid support is one of the earliest and most crucial steps in the process. Interfering with structural features that are important for identification of a target protein will be detrimental to binding affinity. Also, many molecules are sensitive to heat or to certain chemicals, such as acid or base, and might be destroyed during the process of immobilization, which therefore needs to be not only efficient, but also mild. The subsequent affinity chromatography step needs to preserve molecular and conformational integrity of both bait compound and proteins in order to result in the desired specific enrichment while ensuring a high level of compatibility with downstream analysis by mass spectrometry. Thus, the right choice of detergent, buffer, and protease inhibitors is also essential. This chapter describes a widely applicable procedure for the immobilization of small molecule drugs and for drug-affinity chromatography with subsequent protein identification by mass spectrometry. PMID- 22065217 TI - Affinity-based chemoproteomics with small molecule-peptide conjugates. AB - In affinity-based chemoproteomics strategies, the direct immobilization of small bioactive probe molecules to a solid support may pose problems with respect to the preservation of the functional activity toward the target proteins. Typically, immobilized molecules on solid supports exhibit lower affinity for target proteins compared to the free parent molecule. This may lead to a failure to specifically capture the target proteins or to unacceptable losses during the washing steps. To circumvent these shortcomings, we have devised small molecule peptide conjugates (SMPCs), which enable wide-ranging experimental strategies for the capturing of protein targets of small molecules from cells or tissues. With the possibilities of synthesizing peptides of tailored biochemical and biophysical properties, SMPCs enable the identification of protein targets of small molecules from cell-lysates and intact cells. Moreover, labeling of these conjugates with fluorophores can provide information on the cellular localization and distribution of the target. PMID- 22065218 TI - A chemical proteomic probe for detecting dehydrogenases: catechol rhodanine. AB - Inherent complexity of the proteome often demands that it be studied as manageable subsets, termed subproteomes. A subproteome can be defined in a number of ways, although a pragmatic approach is to define it based on common features in an active site that lead to binding of a common small molecule ligand (e.g., a cofactor or a cross-reactive drug lead). The subproteome, so defined, can be purified using that common ligand tethered to a resin, with affinity chromatography. Affinity purification of a subproteome is described in the next chapter. That subproteome can then be analyzed using a common ligand probe, such as a fluorescent common ligand that can be used to stain members of the subproteome in a native gel. Here, we describe such a fluorescent probe, based on a catechol rhodanine acetic acid (CRAA) ligand that binds to dehydrogenases. The CRAA ligand is fluorescent and binds to dehydrogenases at pH > 7, and hence can be used effectively to stain dehydrogenases in native gels to identify what subset of proteins in a mixture are dehydrogenases. Furthermore, if one is designing inhibitors to target one or more of these dehydrogenases, the CRAA staining can be performed in a competitive assay format, with or without inhibitor, to assess the selectivity of the inhibitor for the targeted dehydrogenase. Finally, the CRAA probe is a privileged scaffold for dehydrogenases, and hence can easily be modified to increase affinity for a given dehydrogenase. PMID- 22065219 TI - Probing proteomes with benzophenone photoprobes. AB - Benzophenone photoprobes represent powerful tools for chemical proteomics. Upon UV irradiation, a benzophenone photoprobe can selectively form a covalent bond with its target protein in complex protein mixtures. Thus, photoprobes can be used to profile a wide variety of proteins in complex proteomes. This chapter describes simple protocols to derivatize fluorenylmethyloxycarbonyl (Fmoc) protected peptide-nucleic-acid adenine (PNA adenine) into a benzophenone photoprobe and its application in photolabeling its target proteins. The method as described does not require specialized equipment for probe synthesis and photolabeling. In addition, the strategy is applicable to recognition motifs other than PNA adenine, such as peptides, to profile their target proteins in complex proteomes. PMID- 22065220 TI - Biotinylated probes for the analysis of protein modification by electrophiles. AB - Formation of covalent protein adducts by lipid electrophiles contributes to diseases and toxicities linked to oxidative stress, but analysis of the adducts presents a challenging analytical problem. We describe selective adduct capture using biotin affinity probes to enrich protein and peptide adducts for analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). One approach employs biotinamidohexanoic acid hydrazide to covalently label residual carbonyl groups on adducts. The other employs alkynyl analogs of lipid electrophiles, which form adducts that can be postlabeled with azidobiotin tags by Cu(+) catalyzed cycloaddition (Click chemistry). To enhance the selectivity of adduct capture, we use an azidobiotin reagent with a photocleavable linker, which allows recovery of adducted proteins and peptides under mild conditions. This approach allows both the identification of protein targets of lipid electrophiles and sequence mapping of the adducts. PMID- 22065221 TI - Profiling of methyltransferases and other S-Adenosyl-L-homocysteine-binding proteins by Capture Compound mass spectrometry. AB - There is a variety of approaches to reduce the complexity of the proteome on the basis of functional small molecule-protein interactions. We describe a generic approach based on trifunctional Capture Compounds, in which the initial equilibrium-driven interaction between a small molecule probe and target proteins is irreversibly fixed upon photo-crosslinking between an independent photo activable reactivity function of the Capture Compound and the surface of the target protein(s). Subsequently, Capture Compound - protein conjugates are isolated from complex biological mixtures via the sorting function of the Capture Compound. Here, we describe the application of a trifunctional Capture Compound that carries the methyltransferase product inhibitor S-Adenosyl-L -homocysteine as the selectivity function for the isolation of methyltransferases from a complex lysate of Escherichia coli DH5alpha cells. Photo-activated crosslinking enhances yield and sensitivity of the experiment, and the specificity can be readily tested for in competition experiments using an excess of free S-Adenosyl L -homocysteine. PMID- 22065222 TI - Identifying cellular targets of small-molecule probes and drugs with biochemical enrichment and SILAC. AB - Sequencing of the human genome in the last decade has not yet led to a concomitant increase in the numbers of novel drug targets. While the pharmaceutical industry has invested heavily in improving drugs for existing protein targets, it has not tended toward a similar investment in experimental approaches to identify cellular targets of drugs. It is striking that the targets of numerous widely used FDA-approved drugs remain unknown. The development of robust, unbiased methods for target identification would greatly enhance our understanding the mechanisms-of-action of small molecules. Cell-based phenotypic screens followed by unbiased target identification have the potential to identify novel combinations of small molecules and their protein targets, shed light on drug polypharmacology, and enable unbiased screening approaches to drug discovery. Classical biochemical enrichment with immobilized small molecules has been used for over four decades but has been limited by issues concerning specificity and sensitivity. The application of mass spectrometry-based quantitative proteomics in combination with these affinity reagents has proven to be especially useful in addressing these common issues in affinity purification experiments. We describe the use of SILAC in identifying proteins that bind small molecule probes and drugs in a cellular context. PMID- 22065223 TI - Determination of kinase inhibitor potencies in cell extracts by competition binding assays and isobaric mass tags. AB - Chemical proteomics offers a unique approach for target identification of small molecule inhibitors directly from cell extracts, thus enabling characterization of target proteins under close to physiological conditions. Here, we describe a competition binding procedure that is based on affinity enrichment of potential target proteins on a probe matrix in the presence of increasing amounts of free test compound in solution. Reduced binding of target proteins to the probe matrix as a function of test compound concentration can be measured and thus, enables calculation of IC(50) values. The method employs quantitative mass spectrometry using isobaric mass tags which enables determination of potency for a large number of target proteins in a single analysis. PMID- 22065224 TI - Affinity-based profiling of dehydrogenase subproteomes. AB - The high cost of drug discovery and development requires more efficient approaches to the identification and inhibition of tractable protein targets. One strategy is to pursue families of proteins that already possess affinity for a drug lead scaffold, where that scaffold plays the dual role of serving (a) when tethered to a resin, as a ligand to purify a subproteome of interest, and (b) as a lead molecule that has the potential for optimization for a given member of the subproteome. Here, we describe an example of the purification of a subproteome using a scaffold tailored to the dehydrogenase family of enzymes. Combined with modern LC-MS/MS methods and subsequent searching of proteome databases, such affinity chromatography strategies can be used to purify and identify any proteins with affinity for the scaffold molecule. The method is exemplified using the CRAA (catechol rhodanine acetic acid) privileged scaffold, which is tailored to dehydrogenases. CRAA affinity column chromatography, combined with LC-MS/MS, is described as a method for profiling dehydrogenase subproteomes. PMID- 22065225 TI - Probing the specificity of protein-protein interactions by quantitative chemical proteomics. AB - Chemical proteomics is a versatile tool to investigate protein-small molecule interactions, but can be extended to probe also secondary binding investigating small molecule-protein 1-protein 2 interactions, providing insight into protein scaffolds. This application of chemical proteomics has in particular been applied extensively to cyclic nucleotide (cAMP, cGMP) signaling. cAMP regulates cellular functions primarily by activating cAMP-dependent protein kinase (PKA). Compartmentalization of PKA plays an important role in the specificity of cAMP signaling events and is mediated by interaction of the regulatory subunit (PKA-R) with A-kinase anchoring proteins (AKAPs), which often form the core of even larger protein machineries. The selective binding of AKAPs to one of the major isoforms PKA-R type I (PKA-RI) and PKA-R type II (PKA-RII) is an important feature of cAMP/PKA signaling. However, this specificity is not well established for most AKAPs. Here, we describe a chemical proteomics approach that combines cAMP-based affinity chromatography with quantitative mass spectrometry to investigate PKA-R isoform/AKAP specificity directly in lysates of cells and tissues of any origin. With this tool, several novel PKA-R/AKAP specificities can be easily resolved. PMID- 22065226 TI - Fluorescence-based proteasome activity profiling. AB - With the proteasome emerging as a therapeutic target for cancer treatment, accurate tools for monitoring proteasome (inhibitor) activity are in demand. In this chapter, we describe the synthesis and use of a fluorescent proteasome activity probe that allows for accurate profiling of proteasomal activity in cell lysates, intact cells, and murine and human patient-derived material, with high sensitivity using SDS-PAGE. The probe allows for direct scanning of the gel for fluorescent emission of the distinct proteasomal subunits and circumvents the use of Western blot analysis. Due to its suitable biochemical and biophysical properties, the fluorescent probe can also be used for confocal laser scanning microscopy and flow cytometry-based experiments. PMID- 22065227 TI - Chemical cross-linking and high-resolution mass spectrometry to study protein drug interactions. AB - This method describes the combination of chemical cross-linking and high resolution mass spectrometry for analyzing conformational changes in target proteins that are induced by drug binding. Our approach is exemplified for detecting conformational changes within the peroxisome proliferator-activated receptor alpha upon binding of low-molecular weight compounds, proving that our strategy provides a basis to efficiently characterize target protein-drug interactions. PMID- 22065228 TI - Monitoring ligand modulation of protein-protein interactions by chemical cross linking and High-Mass MALDI mass spectrometry. AB - Analyzing the effect of ligands on protein-protein interactions is important to better understand the cellular processes. In vitro characterization of these modulations remains challenging because of the drawbacks associated with the analysis of noncovalent interactions. To facilitate the analysis, stabilization of the protein complex by chemical cross-linking followed by High-Mass MALDI mass spectrometry is a recently developed method offering several advantages: No need for immobilization or special tags, the analysis is possible directly on wild type protein complexes, no need for buffer exchange, large applicability range for any type of protein complex from 0 to 1,500 kDa. Using this method, we analyzed the effect of the inhibitors Nutlin-3a and Nutlin-3b on the protein complex MDM2-p53. Using this fast and sensitive method, the IC(50) values of these inhibitors have been determined. PMID- 22065229 TI - Time-controlled transcardiac perfusion crosslinking for in vivo interactome studies. AB - The time-controlled transcardiac perfusion crosslinking (tcTPC) method differs from conventional perfusion fixation in that the crosslinking reagent is administered throughout the circulatory system for only a relatively short period of time, thereby allowing limited crosslinking to occur. Bait protein complexes are isolated by affinity capture (AC) under stringent conditions and are recovered from the AC matrix by acidic elution. Affinity-purified proteins are reduced, alkylated, and digested with a specific endoproteinase, such as trypsin. Subsequently, peptides are isotopically labeled, separated by reversed-phase chromatography and analyzed by quantitative tandem mass spectrometry (MS/MS). The proteins crosslinked to the bait protein during tcTPC are identified by database searches with conventional protein identification software. The tcTPC strategy offers unique advantages over alternative approaches for studying a subset of protein complexes which require a particular environment for their structural integrity, such as membrane protein complexes that are notorious for their tendency to dissociate upon detergent solubilization. The sensitivity and utility of this method are influenced by the spatial distribution of chemical groups within the bait protein complexes that can engage in productive crosslinks. PMID- 22065230 TI - Ligand discovery using small-molecule microarrays. AB - Genome-wide association studies and genetic linkage studies have created a growing list of proteins related to disease. Small molecules can serve as useful probes of function for these proteins in a cellular setting or may serve as leads for therapeutic development. High-throughput and general binding assays may provide a path for discovering small molecules that target proteins for which little is known about structure or function or for which conventional functional assays have failed. One such binding assay involves small-molecule microarrays (SMMs) containing compounds that have been arrayed and immobilized onto a solid support. The SMMs can be incubated with a protein target of interest and protein small molecule interactions may be detected using a variety of fluorescent readouts. Several suitable methods for manufacturing SMMs exist and different immobilization methods may be more or less preferable for any given application. Here, we describe protocols for covalent capture of small molecules using an isocyanate-coated glass surface and detection of binding using purified protein. PMID- 22065231 TI - Working with small molecules: preparing and storing stock solutions and determination of kinetic solubility. AB - The handling of organic compounds in the laboratory requires the use of organic (co-) solvents to mediate solubility. Advantages and disadvantages of the widely used solvent dimethylsulfoxide (DMSO) are discussed, and guidelines for dissolution and storage of compounds are given. Finally, nephelometry is introduced as a fast method to determine the kinetic solubility of a compound. PMID- 22065232 TI - A database for chemical proteomics: ChEBI. AB - Chemical proteomics is concerned with the identification of protein targets interacting with small molecules. Hence, the availability of a high quality and free resource storing small molecules is essential for the future development of the field. The Chemical Entities of Biological Interest (ChEBI) database is one such database. The scope of ChEBI includes any constitutionally or isotopically distinct atom, molecule, ion, ion pair, radical, radical ion, complex, conformer, etc., identifiable as a separately distinguishable entity. These entities in question are either products of nature or synthetic products used to intervene in the processes of living organisms. In addition, ChEBI contains a chemical ontology which relates the small molecules with each other thereby making it easier for users to discover data. The ontology also describes the biological roles that the small molecules are active in. The ChEBI database also provides a central reference point in which to access a variety of bioinformatics data points such as pathways and their biochemical reactions; expression data; protein sequence and structures. PMID- 22065233 TI - Working with small molecules: rules-of-thumb of "drug likeness". AB - Based on analyses of existing small organic drug molecules, a set of "rules-of thumb" have been devised to assess the likeness of a small molecule under study to those existing drugs in terms of physicochemical and topological properties. These rules can be used to estimate the likelihood of a small molecule to possess the desired efficacy, pharmacokinetic/pharmacodynamic properties, and toxicity profiles to eventually become a drug, and therefore, whether it justifies further experimental work and development. These rules are particularly useful when selecting a chemical starting point for a given project or choosing a chemical series to focus when multiple series are available. Caution should be paid, however, not to overly rely on these rules for decision-making, since these rules are restricted by knowledge of existing drugs. Novel chemotypes and/or targets may be exceptions. PMID- 22065234 TI - Adherence to HIV treatment and care among previously homeless jail detainees. AB - HIV-infected persons entering the criminal justice system (CJS) often experience suboptimal healthcare system engagement and social instability, including homelessness. We evaluated surveys from a multisite study of 743 HIV-infected jail detainees prescribed or eligible for antiretroviral therapy (ART) to understand correlates of healthcare engagement prior to incarceration, focusing on differences by housing status. Dependent variables of healthcare engagement were: (1) having an HIV provider, (2) taking ART, and (3) being adherent (>=95% of prescribed doses) to ART during the week before incarceration. Homeless subjects, compared to their housed counterparts, were significantly less likely to be engaged in healthcare using any measure. Despite Ryan White funding availability, insurance coverage remains insufficient among those entering jails, and having health insurance was the most significant factor correlated with having an HIV provider and taking ART. Individuals interfacing with the CJS, especially those unstably housed, need innovative interventions to facilitate healthcare access and retention. PMID- 22065235 TI - The development and psychometric properties of the HIV and Abuse Related Shame Inventory (HARSI). AB - Shame has been shown to predict sexual HIV transmission risk behavior, medication non-adherence, symptomatic HIV or AIDS, and symptoms of depression and PTSD. However, there remains a dearth of tools to measure the specific constructs of HIV-related and sexual abuse-related shame. To ameliorate this gap, we present a 31-item measure that assesses HIV and sexual abuse-related shame, and the impact of shame on HIV-related health behaviors. A diverse sample of 271 HIV-positive men and women who were sexually abused as children completed the HIV and Abuse Related Shame Inventory (HARSI) among other measures. An exploratory factor analysis supported the retention of three-factors, explaining 56.7% of the sample variance. These internally consistent factors showed good test-retest reliability, and sound convergent and divergent validity using eight well established HIV specific and general psychosocial criterion measures. Unlike stigma or discrimination, shame is potentially alterable through individually focused interventions, making the measurement of shame clinically meaningful. PMID- 22065236 TI - 1-(2-Hy-droxy-2-phenyl-eth-yl)-3-(4-meth-oxy-phen-yl)urea. AB - In the title compound, C(16)H(18)N(2)O(3), the dihedral angle between the 4-meth oxy-phenyl ring and the urea group is 35.6 (2) degrees . The H atoms of the urea NH groups are positioned syn to each other. In the crystal, inter-molecular N-H?O and O-H?O hydrogen bonds link the mol-ecules into a two-dimensional array in the ac plane; the carbonyl-O atom is trifurcated. PMID- 22065237 TI - Difference in intraosseous blood vessel volume and number in osteoporotic model mice induced by spinal cord injury and sciatic nerve resection. AB - In the present study, we examined intraosseous blood vessel parameters of the tibial metaphysis in mice using microcomputed tomography (uCT) to investigate the relationship between post-nerve-injury osteoporosis and local intraosseous blood vessel volume and number. Mice were randomly divided into groups receiving spinal cord injury (SCI), sciatic nerve resection group (NX), or intact controls (30 mice/group). Four weeks after surgery, mice were perfused with silicone and the distribution of intraosseous blood vessels analyzed by MUCT. The bone density, MUCT microstructure, biomechanical properties, and the immunohistochemical and biochemical indicators of angiogenesis were also measured. The SCI group showed significantly reduced tibial metaphysis bone density, MUCT bone microstructure, tibial biomechanical properties, indicators of angiogenesis, and intraosseous blood vessel parameters compared to the NX group. Furthermore, the spinal cord injured mice exhibited significantly decreased intraosseous blood vessel volume and number during the development of osteoporosis. In conclusion, these data suggest that decreased intraosseous blood vessel volume and number may play an important role in the development of post-nerve-injury osteoporosis. PMID- 22065238 TI - Children and adolescents treated with neridronate for osteogenesis imperfecta show no evidence of any osteonecrosis of the jaw. AB - Over recent years, several reports have been published on unusual cases of osteonecrosis of the jaw (ONJ) in adults using second- and third-generation nitrogen-containing bisphosphonates such as pamidronate, alendronate, risedronate and zoledronate, but no case has ever been reported either in children or in adult patients taking neridronate. Children and adolescents affected by osteogenesis imperfecta (OI) could belong to a high-risk group for ONJ because bone fragility in OI is associated with a connective tissue malfunction. The purpose of this study is to evaluate the incidence of ONJ in a pediatric population treated with neridronate for OI. A total of 102 pediatric patients with OI who received neridronate infusions for a mean of 6.81 years (SD +/- 3.06 years) were clinically assessed for possible ONJ. Eligibility criteria for participation included patients between 1.2 and 24 years old who received cyclical neridronate infusions for at least 1 year. All the patients were reviewed to determine duration, dosage and cumulative dose of their bisphosphonate therapy and were examined clinically to assess their oral health status. We have not demonstrated any occurrence of ONJ in our patients. In conclusion, at the moment insufficient data are available to prove a greater risk of ONJ in children with OI than in children affected by other forms of bone fragility. However, cases may emerge in future because the risk of ONJ seems to be related to the cumulative dose and the duration of therapy. PMID- 22065239 TI - Ethyl 2-[2-(3-meth-oxy-phen-yl)hydrazinyl-idene]-3-oxobutano-ate. AB - The title compound, C(13)H(16)N(2)O(4), is approximately planar (r.m.s. deviation = 0.065 A for the 19 non-H atoms). An intra-molecular N-H?O hydrogen bond generates an S(6) ring motif and the mol-ecule adopts an E conformation with respect to the central C=N double bond. In the crystal, pairs of inter-molecular C-H?O hydrogen bonds link adjacent mol-ecules into inversion dimers. The crystal structure also features weak C-H?pi inter-actions. PMID- 22065240 TI - Development of a new Knee Society scoring system. AB - BACKGROUND: The Knee Society Clinical Rating System was developed in 1989 and has been widely adopted. However, with the increased demand for TKA, there is a need for a new, validated scoring system to better characterize the expectations, satisfaction, and physical activities of the younger, more diverse population of TKA patients. QUESTIONS/PURPOSES: We developed and validated a new Knee Society Scoring System. METHODS: We developed the new knee scoring system in two stages. Initially, a comprehensive survey of activities was developed and administered to 101 unilateral TKA patients (53 women, 48 men). A prototype knee scoring instrument was developed from the responses to the survey and administered to 497 patients (204 men, 293 women; 243 postoperatively, 254 preoperatively) at 15 medical institutions within the United States and Canada. Objective and subjective data were analyzed using standard statistical and psychometric procedures and compared to the Knee Injury and Osteoarthritis Score and SF-12 scores for validation. Based on this analysis, minor modifications led to the new Knee Society Scoring System. RESULTS: We found the new Knee Society Scoring System to be broadly applicable and to accurately characterize patient outcomes after TKA. Statistical analysis confirmed the internal consistency, construct and convergent validity, and reliability of the separate subscale measures. CONCLUSIONS: The new Knee Society Scoring System is a validated instrument based on surgeon- and patient-generated data, adapted to the diverse lifestyles and activities of contemporary patients with TKA. This assessment tool allows surgeons to appreciate differences in the priorities of individual patients and the interplay among function, expectation, symptoms, and satisfaction after TKA. PMID- 22065241 TI - 1-Methyl-3,3-bis-[(4-methyl-phen-yl)sulfan-yl]piperidin-2-one. AB - The piperidone ring in the title compound, C(20)H(23)NOS(2), has a half-chair distorted to a twisted-boat conformation [Q(T) = 0.5200 (17) A]. One of the S bound benzene rings is almost perpendicular to the least-squares plane through the piperidone ring, whereas the other is not [dihedral angles = 75.28 (5) and 46.41 (5) A, respectively]. In the crystal, the presence of C-H?O and C-H?pi inter-actions leads to the formation of supra-molecular layers in the ab plane. PMID- 22065242 TI - Living the categorical imperative: autistic perspectives on lying and truth telling-between Kant and care ethics. AB - Lying is a common phenomenon amongst human beings. It seems to play a role in making social interactions run more smoothly. Too much honesty can be regarded as impolite or downright rude. Remarkably, lying is not a common phenomenon amongst normally intelligent human beings who are on the autism spectrum. They appear to be 'attractively morally innocent' and seem to have an above average moral conscientious objection against deception. In this paper, the behavior of persons with autism with regard to deception and truthfulness will be discussed in the light of two different ethical theories, illustrated by fragments from autobiographies of persons with autism. A systemizing 'Kantian' and an empathizing 'ethics of care' perspective reveal insights on high-functioning autism, truthfulness and moral behavior. Both perspectives are problematic from the point of view of a moral agent with autism. High-functioning persons with autism are, generally speaking, strong systemizes and weak empathizers. Particularly, they lack 'cognitive empathy' which would allow them to understand the position of the other person. Instead, some tend to invent a set of rules that makes their behavior compatible with the expectations of others. From a Kantian point of view, the autistic tendency to always tell the truth appears praiseworthy and should not be changed, though it creates problems in the social life of persons with autism. From a care ethics perspective, on the other hand, a way should be found to allow the high-functioning persons with autism to respect the feelings and needs of other persons as sometimes overruling the duty of truthfulness. We suggest this may even entail 'morally educating' children and adolescents with autism to become socially skilled empathic 'liars'. PMID- 22065243 TI - DLG5 P1371Q is associated with inflammatory bowel disease and complementary to R30Q in disease susceptibility. AB - BACKGROUND AND PURPOSE: The SNP R30Q (rs1248696) within the discs large homolog 5 (DLG5) gene has been associated with inflammatory bowel disease (IBD). In this study, we examined the genetic association of another DLG5 SNP P1371Q (rs2289310) with IBD and its interaction with R30Q in disease susceptibility. METHODS: A total of 213 IBD patients [106 familial; 59 Crohn's disease (CD) and 47 ulcerative colitis (UC)] and 107 sporadic [57 CD and 50 UC] were included in this study. Controls included 139 non-diseased family members of IBD patients and 170 unrelated healthy subjects. Genotypes for P1371Q and G1066G polymorphisms were determined by PCR-based RFLP. Epistasis between P1371Q and R30Q in disease susceptibility was analysed using a novel statistical model. RESULTS: P1371Q was associated with IBD (OR = 2.335, 95% CI = 1.097-4.972, p = 0.0246), however, the synonymous variant G1066G (rs1648234) was not. Gender distribution analysis revealed the A allele of P1371Q was significantly associated with IBD in women (OR = 3.765, 95% CI = 1.307-10.85, p = 0.0095). Modeling interaction between P1371Q and R30Q showed a significant increase in disease association (OR = 2.265, 95% CI = 1.405-3.652, p = 0.0007) incidence for sporadic and familial IBD patients. Further epistatic analysis identified an increased significance in the association of gender with IBD (OR = 4.311, 95% CI = 2.101-8.846, p = 0.0001). CONCLUSIONS: DLG5 P1371Q was associated with IBD and this association was female specific. A significant epistatic interaction between P1371Q and R30Q was observed, suggesting that P1371Q is complementary to R30Q, with R30Q exhibiting a dominant effect in IBD susceptibility. PMID- 22065244 TI - Tigecycline accelerates staphylococcal-infected burn wound healing through matrix metalloproteinase-9 modulation. AB - OBJECTIVES: We investigated the in vivo efficacy of tigecycline, a new glycylcycline (a tetracycline derivative), in the management of methicillin resistant Staphylococcus aureus (MRSA)-infected experimental surgical wounds in rats. The main outcome measures were quantitative bacterial culture, histological examination and immunohistochemical expression of matrix metalloproteinase-9 (MMP 9) and collagen IV. METHODS: An animal model was used to compare the in vivo efficacy of teicoplanin and tigecycline in the treatment of burn wound infections by S. aureus. A copper bar, heated in boiling water, was placed on the paraspinal site of each rat, resulting in full thickness burns. A small gauze was placed over each burn and then inoculated with 5 * 10(7) cfu of S. aureus ATCC 43300. To mimic the clinical situation in burn patients, surgical debridement was performed 48 h after the injury. The wounds were left to heal by secondary intention. The study included an uninfected control group that did not receive any treatment, a contaminated group that did not receive any treatment, and two contaminated groups treated with intraperitoneal tigecycline (2 mg/kg) and teicoplanin (7 mg/kg), respectively. RESULTS: All antibiotic treatments were significantly effective. Tigecycline showed the highest antimicrobial activity, with a better impact on histological results. Infected rats treated with tigecycline showed a significant decrease in MMP-9 expression both in epithelium and in dermis compared with rats treated with teicoplanin. CONCLUSIONS: Tigecycline, besides its antimicrobial activity, exerts an important modulatory effect on MMP-9, accelerating wound healing in staphylococcal-infected burns. PMID- 22065245 TI - In vitro evaluation of marginal and internal adaptation after occlusal stressing of indirect class II composite restorations with different resinous bases and interface treatments. "Post-fatigue adaptation of indirect composite restorations". AB - The present study evaluated the influence of different composite bases and surface treatments on marginal and internal adaptation of class II indirect composite restorations, after simulated occlusal loading. Thirty-two class II inlay cavities were prepared on human third molars, with margins located in cementum. A 1-mm composite base extending up to the cervical margins was applied on all dentin surfaces in the experimental groups; impressions were made and composite inlays fabricated. The following experimental conditions were tested: no liner (control group), flowable composite treated with soft air abrasion (experiment 1), flowable composite sandblasted (experiment 2) and restorative composite sandblasted (experiment 3). All specimens were submitted to 1,000,000 cycles with a 100-N eccentric load. Tooth-restoration margins were analysed semi quantitatively by scanning electron microscopy before and after loading; internal adaptation was also evaluated after test completion. The percentage of perfect adaptation in enamel was 79.5% to 92.7% before loading and 73.3% to 81.9% after loading. Perfect adaptation to dentin was reduced before loading (54.8% to 77.6%) and after loading (41.9% to 63%), but no difference was found among groups for pre- and post-loading conditions. No debonding occurred between the base and composite luting. A significant, negative influence of cyclic loading was observed. The results of the present study support the use of flowable or restorative composites as base/liner underneath large class II restorations. Soft air abrasion represents a potential alternative to airborne particle abrasion for treating cavities before cementation. The application of a composite base underneath indirect composite restorations represents a feasible non-invasive alternative to surgical crown lengthening to relocate cavity margins from an intra-crevicular to supra-gingival position. PMID- 22065246 TI - Expression and secretion levels of Th1 and Th2 cytokines in patients with aggressive periodontitis. AB - The role of Th1 and Th2 cytokines in the pathogenesis of aggressive periodontitis has not been previously examined. The aim of this study was to analyse the expression and production of IL-2, IFN-gamma, IL-4 and IL-13 in CD4+ cells from the peripheral blood of patients with aggressive periodontitis (AgP) and periodontally healthy controls. Gene expression was analysed in inactivated and activated CD4+ cells by real-time PCR. Cells were activated for 4, 8 and 24 h with anti-CD3/CD28 antibody, phytohemagglutinin (PHA), and Porphyromonas gingivalis (P.g.) outer membrane protein (OMP). Protein levels were measured in supernatants of activated CD4+ cells by bead-based immunoassay (CBA). Statistics were performed using U test (p < 0.05). In controls, IL-4 expression was increased in inactivated CD4+ cells (p = 0.05), and IFN-gamma and IL-2 expressions were increased in activated CD4+ cells: IFN-gamma with anti-CD3/anti CD28, P.g. OMP and PHA (p < 0.05); IL-2 with P.g. OMP and PHA (p < 0.05). In patients, although IL-4 and IL-13 expressions were higher in activated CD4+ cells, there were no differences compared to controls. The production of IL-4 and IL-2 was higher in the patients' CD4+ cells activated with PHA (p < 0.05). Although the results showed a predominantly Th1 mRNA profile in activated CD4+ cells of controls, protein concentrations showed no clear Th1 or Th2 profiles. The functional pathways of the Th cell immune response in aggressive periodontitis are still not well understood in order to develop individualised diagnostic and treatment plans. PMID- 22065247 TI - Possible hazardous effects of hydrofluoric acid and recommendations for treatment approach: a review. AB - Hydrofluoric acid (HF) is commonly used for conditioning the glass ceramics either prior to cementation or for intraoral repair in prosthetic and restorative dentistry. The present study offers a review of chemical properties of HF used, highlight the possible hazardous effects of this agent, and to recommend the treatment approach for potential risks. Available published information documented in PubMed, Medline, and Picarta literature databases was reviewed. Additional information was derived from scientific reports, medical and chemical textbooks, handbooks, product information, manufacturers' instructions, Internet web sites of the HF manufacturers. No report was found on the incidence of the hazardous effects of HF in dentistry. Reports from other fields presented incidences of acute and chronic symptoms in exposure to HF. While acute symptoms include skin or nail burns, chronic ones involve systemic toxicity, eye injuries, inhalation and ingestion-related symptoms that can be even fatal. HF can be harmful and particularly aggressive to soft tissues, but symptoms may not be apparent immediately after exposure. The hazardous effects are not based on the pH value, but on the toxicity of HF. Potential hazards of HF known from other applications than dentistry should be considered also in dental applications. Especially the clinicians, who often deal with adhesive cementation or repair of glass ceramics, should take necessary precautions for possible hazards of HF. PMID- 22065248 TI - Identification of valid housekeeping genes for quantitative RT-PCR analysis of cardiosphere-derived cells preconditioned under hypoxia or with prolyl-4 hydroxylase inhibitors. AB - Infarction irreversibly damages the heart, with formation of an akinetic scar that may lead to heart failure. Endogenous cardiac stem cells (CSCs) are a promising candidate cell source for restoring lost tissue and thereby preventing heart failure. CSCs may be isolated in vitro, via the formation of cardiospheres, to give cardiosphere-derived cells (CDCs). Although qRT-PCR analyses of CDCs have been performed, no justification for the selection of the housekeeping gene has been published. Here, we evaluated the most suitable housekeeping gene for RNA expression analysis in CDCs cultured under normoxia, hypoxia or with prolyl-4 hydroxylase inhibitors (PHDIs), from both neonatal and adult rats, to determine the effects of ageing and different culture conditions on the stability of the housekeeping gene for CDCs. Six candidate housekeeping genes, [glyceraldehyde-3 phosphate dehydrogenase (GAPDH), beta-actin (Actb), hypoxanthine phosphoribosyltransferase 1 (HPRT-1), beta-2-microtubulin (beta2M), 60S acidic ribosomal protein large P1 (RPLP-1) and TATA box binding protein (Tbp)] were evaluated in this study. Analysis using geNorm and NormFinder revealed that GAPDH was the most constant housekeeping gene among all genes tested under normoxia for both neonatal and adult CDCs, whereas Actb was the most stable housekeeping gene under hypoxia. For the PHDI-treated CDCs, overall, GADPH, Actb and beta2M were more consistently expressed, whereas HPRT-1, RPLP-1 and Tbp showed unstable expression. The ranking for beta2M, HPRT-1 and RPLP-1 stability was different for neonatal and adult cells, indicating that expression of these genes was age dependent. Lastly, independent of age or culture conditions, Tbp was the least stable housekeeping gene. In conclusion, a combination of Actb and GADPH gave the most reliable normalization for comparative analyses of gene transcription in neonatal and adult rat CDCs preconditioned by hypoxia or PHDIs. PMID- 22065249 TI - Challenges in lung transplantation. AB - Lung transplantation is an established therapy for end-stage pulmonary disorders in selected patients without significant comorbidities. The particular constraints associated with organ transplantation from deceased donors involve specific allocation rules in order to optimise the medical efficacy of the procedure. Comparison of different policies adopted by national transplant agencies reveals that an optimal and unique allocation system is an elusive goal, and that practical, geographical and logistic parameters must be taken into account. A solution to attenuate the imbalance between the number of lung transplant candidates and the limited availability of organs is to consider marginal donors. In particular, assessment and restoration of gas exchange capacity ex vivo in explanted lungs is a new and promising approach that some lung transplant programmes have started to apply in clinical practice. Chronic lung allograft dysfunction, and especially bronchiolitis obliterans, remains the major medium- and long-term problem in lung transplantation with a major impact on survival. Although there is to date no cure for established bronchiolitis obliterans, new preventive strategies have the potential to limit the burden of this feared complication. Unfortunately, randomised prospective studies are infrequent in the field of lung transplantation, and data obtained from larger studies involving kidney or liver recipients are not always relevant for this purpose. PMID- 22065250 TI - Cultivable bacteria from ancient algal mats from the McMurdo Dry Valleys, Antarctica. AB - The McMurdo Dry Valleys in Antarctica are a favorable location for preservation of dormant microbes due to their persistent cold and dry climate. In this study, we examined cultivable bacteria in a series of algal mat samples ranging from 8 to 26539 years old. Cultivable bacteria were found in all samples except one (12303 years old), but abundance and diversity of cultivable bacteria decreased with increasing sample age. Only members of the Actinobacteria, Bacteroidetes, and Firmicutes were found in the ancient samples, whereas bacteria in the 8-year old sample also included Cyanobacteria, Proteobacteria, and Deinococcus-Thermus. Isolates of the Gram-positive spore-forming bacterium Sporosarcina were found in 5 of 8 samples. The growth of these isolates at different temperatures was related to the phylogenetic distance among genotypes measured by BOX-PCR. These findings suggest that adaptation to growth at different temperatures had occurred among Sporosarcina genotypes in the Dry Valleys, causing the existence of physiologically distinct but closely related genotypes. Additionally, fully psychrophilic isolates (that grew at 15 degrees C, but not 25 degrees C) were found in ancient samples, but not in the modern sample. The preservation of viable bacteria in the Dry Valleys could potentially represent a legacy of bacteria that impacts on current microbial communities of this environment. PMID- 22065251 TI - (R*,S*)-(+/-)-1-(2-{[2,8-Bis(trifluoromethyl)quinolin-4 yl](hydroxy)methyl}piperidin-1-yl)ethanone methanol monosolvate. AB - The title mefloquine derivative has been crystallized as its 1:1 methanol solvate, C(19)H(18)F(6)N(2)O(2).CH(3)OH. Each of the meth-ine-hydroxyl residue [the C-C-C-O torsion angle is -16.35 (17) degrees ] and the piperidinyl group [distorted chair conformation] lies to one side of the quinolinyl ring system. The hydroxyl and carbonyl groups lie to either side of the mol-ecule, enabling their participation in inter-molecular inter-actions. Thus, the hydroxyl and carbonyl groups of two centrosymmetrically related mol-ecules are bridged by two methanol mol-ecules via O-H?O hydrogen bonds, leading to a four-mol-ecule aggregate. These are linked into a supra-molecular chain along the a axis via C H?O inter-actions involving the hydroxyl-O atom. The chains assemble into layers that inter-digitate along the c axis being connected by C-H?F inter-actions. PMID- 22065252 TI - Testing standard and modular designs for psychotherapy treating depression, anxiety, and conduct problems in youth: a randomized effectiveness trial. AB - CONTEXT: Decades of randomized controlled trials have produced separate evidence based treatments for depression, anxiety, and conduct problems in youth, but these treatments are not often used in clinical practice, and they produce mixed results in trials with the comorbid, complex youths seen in practice. An integrative, modular redesign may help. OBJECTIVE: Standard/separate and modular/integrated arrangements of evidence-based treatments for depression, anxiety, and conduct problems in youth were compared with usual care treatment, with the modular design permitting a multidisorder focus and a flexible application of treatment procedures. DESIGN: Randomized effectiveness trial. SETTING: Ten outpatient clinical service organizations in Massachusetts and Hawaii. PARTICIPANTS: A total of 84 community clinicians were randomly assigned to 1 of 3 conditions for the treatment of 174 clinically referred youths who were 7 to 13 years of age (70% of these youths were boys, and 45% were white). The study was conducted during the period from January 12, 2005 to May 8, 2009. INTERVENTIONS: Standard manual treatment (59 youths [34% of the sample]; cognitive behavioral therapy for depression, cognitive behavioral therapy for anxiety, and behavioral parent training for conduct problems), modular treatment (62 youths [36%]; integrating the procedures of the 3 separate treatments), and usual care (53 youths [30%]). MAIN OUTCOME MEASURES: Outcomes were assessed using weekly youth and parent assessments. These assessments relied on a standardized Brief Problem Checklist and a patient-generated Top Problems Assessment (ie, the severity ratings on the problems that the youths and parents had identified as most important). We also conducted a standardized diagnostic assessment before and after treatment. RESULTS: Mixed effects regression analyses showed that modular treatment produced significantly steeper trajectories of improvement than usual care and standard treatment on multiple Brief Problem Checklist and Top Problems Assessment measures. Youths receiving modular treatment also had significantly fewer diagnoses than youths receiving usual care after treatment. In contrast, outcomes of standard manual treatment did not differ significantly from outcomes of usual care. CONCLUSIONS: The modular approach outperformed usual care and standard evidence-based treatments on multiple clinical outcome measures. The modular approach may be a promising way to build on the strengths of evidence-based treatments, improving their utility and effectiveness with referred youths in clinical practice settings. Trial Registration clinicaltrials.gov Identifier: NCT01178554. PMID- 22065253 TI - A multisite study of the clinical diagnosis of different autism spectrum disorders. AB - CONTEXT: Best-estimate clinical diagnoses of specific autism spectrum disorders (autistic disorder, pervasive developmental disorder-not otherwise specified, and Asperger syndrome) have been used as the diagnostic gold standard, even when information from standardized instruments is available. OBJECTIVE: To determine whether the relationships between behavioral phenotypes and clinical diagnoses of different autism spectrum disorders vary across 12 university-based sites. DESIGN: Multisite observational study collecting clinical phenotype data (diagnostic, developmental, and demographic) for genetic research. Classification trees were used to identify characteristics that predicted diagnosis across and within sites. SETTING: Participants were recruited through 12 university-based autism service providers into a genetic study of autism. PARTICIPANTS: A total of 2102 probands (1814 male probands) between 4 and 18 years of age (mean [SD] age, 8.93 [3.5] years) who met autism spectrum criteria on the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule and who had a clinical diagnosis of an autism spectrum disorder. MAIN OUTCOME MEASURE: Best estimate clinical diagnoses predicted by standardized scores from diagnostic, cognitive, and behavioral measures. RESULTS: Although distributions of scores on standardized measures were similar across sites, significant site differences emerged in best-estimate clinical diagnoses of specific autism spectrum disorders. Relationships between clinical diagnoses and standardized scores, particularly verbal IQ, language level, and core diagnostic features, varied across sites in weighting of information and cutoffs. CONCLUSIONS: Clinical distinctions among categorical diagnostic subtypes of autism spectrum disorders were not reliable even across sites with well-documented fidelity using standardized diagnostic instruments. Results support the move from existing subgroupings of autism spectrum disorders to dimensional descriptions of core features of social affect and fixated, repetitive behaviors, together with characteristics such as language level and cognitive function. PMID- 22065254 TI - Epigenetic signatures of autism: trimethylated H3K4 landscapes in prefrontal neurons. AB - CONTEXT: Neuronal dysfunction in cerebral cortex and other brain regions could contribute to the cognitive and behavioral defects in autism. OBJECTIVE: To characterize epigenetic signatures of autism in prefrontal cortex neurons. DESIGN: We performed fluorescence-activated sorting and separation of neuronal and nonneuronal nuclei from postmortem prefrontal cortex, digested the chromatin with micrococcal nuclease, and deeply sequenced the DNA from the mononucleosomes with trimethylated H3K4 (H3K4me3), a histone mark associated with transcriptional regulation. Approximately 15 billion base pairs of H3K4me3-enriched sequences were collected from 32 brains. SETTING: Academic medical center. PARTICIPANTS: A total of 16 subjects diagnosed as having autism and 16 control subjects ranging in age from 0.5 to 70 years. MAIN OUTCOME MEASURES: Identification of genomic loci showing autism-associated H3K4me3 changes in prefrontal cortex neurons. RESULTS: Subjects with autism showed no evidence for generalized disruption of the developmentally regulated remodeling of the H3K4me3 landscape that defines normal prefrontal cortex neurons in early infancy. However, excess spreading of H3K4me3 from the transcription start sites into downstream gene bodies and upstream promoters was observed specifically in neuronal chromatin from 4 of 16 autism cases but not in controls. Variable subsets of autism cases exhibit altered H3K4me3 peaks at numerous genes regulating neuronal connectivity, social behaviors, and cognition, often in conjunction with altered expression of the corresponding transcripts. Autism-associated H3K4me3 peaks were significantly enriched in genes and loci implicated in neurodevelopmental diseases. CONCLUSIONS: Prefrontal cortex neurons from subjects with autism show changes in chromatin structures at hundreds of loci genome-wide, revealing considerable overlap between genetic and epigenetic risk maps of developmental brain disorders. PMID- 22065255 TI - Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. AB - CONTEXT: No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. OBJECTIVE: To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription opioids. DESIGN: Multisite, randomized clinical trial using a 2 phase adaptive treatment research design. Brief treatment (phase 1) included 2 week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine naloxone treatment, 4-week taper, and 8-week postmedication follow-up. SETTING: Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription opioids. INTERVENTIONS: In both phases, patients were randomized to standard medical management (SMM) or SMM plus opioid dependence counseling; all received buprenorphine-naloxone. MAIN OUTCOME MEASURES: Predefined "successful outcome" in each phase: composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports. RESULTS: During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus opioid dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P < .001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower phase 2 success rates while taking buprenorphine-naloxone. CONCLUSIONS: Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM. PMID- 22065256 TI - Doppler tissue energy and stress echocardiography in the diagnosis of myocardial contusion in canines. AB - We sought to evaluate the significance of Doppler tissue energy (DTE) and stressed echocardiography for diagnosing myocardial contusion (MC) in canines. Ten adult healthy dogs were anesthetized (3% pentobarbital sodium/i.v.) and impacted by BIM-II biological impact machine to induce MC. Conventional and stressed echocardiographies were used for segmental abnormal ventricular wall motions; DTE was also used to detect the abnormal ventricular wall motions and areas of injured myocardial fibers after MC, and the results were compared with those of triphenyl tetrazolium chloride (TTC) staining. The data show that both conventional and stressed echocardiographies identified ventricular wall segmental abnormal motions or even aneurysms. These segments were mainly distributed over the front and middle interventricular walls and anterolateral ventricular wall. The ventricular wall motion scoring and wall motion segment index (WMSI) increased remarkably after MC induction. Compared with TTC staining, the conventional echocardiography showed 100% sensitivity and 66.67% specificity, whereas the stressed echocardiography displayed 100% sensitivity and 88.89% specificity. DTE showed both the sensitivity and specificity of 100% for MC diagnosis. Thus, DTE has higher specificity than conventional and stressed echocardiographies. In conclusion, both DTE and stress echocardiography have higher clinical value for MC diagnosis in canines. PMID- 22065257 TI - Identification of transcriptome profiles and signaling pathways for the allelochemical juglone in rice roots. AB - Juglone (5-hydroxy-1,4-naphthoquinone) is known allelochemical, but its molecular mode of action is not well understood. We found that juglone induced reactive oxygen species production and calcium accumulation. To gain more insight into these cellular responses, we performed large-scale analysis of the rice transcriptome during juglone stress. Exposure to juglone triggered changes in transcript levels of genes related to cell growth, cell wall formation, chemical detoxification, abiotic stress response and epigenesis. The most predominant transcription-factor families were AP2/ERF, HSF, NAC, C2H2, WRKY, MYB and GRAS. Gene expression profiling of juglone-treated rice roots revealed upregulated signaling and biosynthesis of abscisic acid and jasmonic acid and inactivation of gibberellic acid. In addition, juglone upregulated the expression of two calcium dependent protein kinases (CDPKs), 6 mitogen-activated protein kinase (MAPK) genes and 1 MAPK gene and markedly increased the activities of a CDPK-like kinase and MAPKs. Further characterization of these juglone-responsive genes may be helpful for better understanding the mechanisms of allelochemical tolerance in plants. PMID- 22065258 TI - Interest in a national research network in surgery in Switzerland. AB - BACKGROUND: Networks are known to improve performance and create synergies. A research network can provide a significant advantage for all parties involved in research in surgery by systematically tracking the outcome of a huge number of patients over a long period of time. The aim of the present study was to investigate the experiences of surgeons with respect to research activities, to evaluate the opinions of surgeons with regard to the development of a national network for research in the field of surgery in Switzerland and to obtain data on how such a network should be designed. METHODS: An anonymous postal survey of board-certified surgeons practising in Switzerland was conducted during summer 2007. The questionnaire included questions related to research activities, the desire to develop a national research network and the design and potential advantages of such a network. Qualitative analyses were performed using Mayring's content analysis. RESULTS: A total of 337 out of 749 (45%) questionnaires were returned. In all, 156/337 (46.3%) surgeons were engaged in research activities. During the past five years, 212/337 (62.9%) of the participants had participated at least in one multi-centre study. Out of 337, 88 (26.1%) surgeons were members of an established research association in Switzerland. Interest in a national surgical research network was reported by 266 (78.9%) participants. The reported advantages were "power" (53.1%), "teamwork effects" (23.7%), "efficiency" (12.2%) and "quality aspects" (8.0%). The most frequently named design proposal was based on a clinic for coordinating research, while the younger participants also suggested a web-based platform. CONCLUSIONS: Due to the significant interest of participants, the establishment of a national research network should be considered. An established clinic for coordinating research alongside an additional web-based platform to target young surgeons could function as an umbrella organisation. PMID- 22065259 TI - Sexual isolation between North American and Bogota strains of Drosophila pseudoobscura. AB - Sexual isolation, the reduced ability of organisms of different species to successfully mate, is one of the reproductive barriers that prevent gene flow between different taxa. Various species-specific signals during courtship are attributed to the sexual isolation between them. Drosophila pseudoobscura has been widely used to study the behavioral and genetic mechanisms underlying selection for sexual isolation, as a model system for speciation. D. pseudoobscura and its sibling species, D. persmilis, live together in many locations but are reproductively isolated from one another. North American geographic strains of D. pseudoobscura from the American West mate at random. Several decades ago, D. pseudoobscura was collected in the vicinity of Bogota, Colombia, and later named the subspecies D. pseudoobscura bogotana. Nearly 5,000 matings were observed in this study. We analyzed mating behavior and cuticular hydrocarbon profiles as well as courtship within and between North American and Bogota strains of D. pseudoobscura. Here we report for the first time that Bogota strains of D. pseudoobscura do show statistically significant sexual isolation from North American strains. In addition, there are quantitative variations in cuticular hydrocarbons as well as in courtship behavior between Bogota and North American strains, and females of both North American and Bogota strains show strong preference for North American strain males having high mating propensities, suggesting that the Bogota strains are at an early stage that could lead to a separate species. PMID- 22065260 TI - Migraine attack triggering a generalised seizure: is this a case of migralepsy or ictal epileptic headache? PMID- 22065261 TI - Who benefits from peer support in psychiatric institutions? AB - This study examines the influence of recovery-oriented peer events on participants' recovery attitudes and explores who benefits most from such events. Changes in participants' recovery attitudes were evaluated (pre, post, follow up), and compared with changes of control groups. Distributions of recovery related values in subgroups were analyzed descriptively. The results of non parametric tests (Friedman) showed participants with significantly higher values in the dimension Recovery is possible directly after the interventions (P = 0.006), but not 6 months later, and not in comparison with members of control groups. On a descriptive level, women, participants with schizophrenia and with two or more episodes of the disorder showed higher recovery-related values compared to men, participants with an affective disorder and only one episode. Within their feedback, organizations and peers express a positive view of peer support, but evidence for a positive impact of the evaluated peer events on recovery attitude is limited. PMID- 22065263 TI - Antibiotic prescribing in ambulatory pediatrics in the United States. AB - BACKGROUND: Antibiotics are commonly prescribed for children with conditions for which they provide no benefit, including viral respiratory infections. Broad spectrum antibiotic use is increasing, which adds unnecessary cost and promotes the development of antibiotic resistance. OBJECTIVE: To provide a nationally representative analysis of antibiotic prescribing in ambulatory pediatrics according to antibiotic classes and diagnostic categories and identify factors associated with broad-spectrum antibiotic prescribing. PATIENTS AND METHODS: We used the National Ambulatory and National Hospital Ambulatory Medical Care surveys from 2006 to 2008, which are nationally representative samples of ambulatory care visits in the United States. We estimated the percentage of visits for patients younger than 18 years for whom antibiotics were prescribed according to antibiotic classes, those considered broad-spectrum, and diagnostic categories. We used multivariable logistic regression to identify demographic and clinical factors that were independently associated with broad-spectrum antibiotic prescribing. RESULTS: Antibiotics were prescribed during 21% of pediatric ambulatory visits; 50% were broad-spectrum, most commonly macrolides. Respiratory conditions accounted for >70% of visits in which both antibiotics and broad-spectrum antibiotics were prescribed. Twenty-three percent of the visits in which antibiotics were prescribed were for respiratory conditions for which antibiotics are not clearly indicated, which accounts for >10 million visits annually. Factors independently associated with broad-spectrum antibiotic prescribing included respiratory conditions for which antibiotics are not indicated, younger patients, visits in the South, and private insurance. CONCLUSIONS: Broad-spectrum antibiotic prescribing in ambulatory pediatrics is extremely common and frequently inappropriate. These findings can inform the development and implementation of antibiotic stewardship efforts in ambulatory care toward the most important geographic regions, diagnostic conditions, and patient populations. PMID- 22065262 TI - Critically ill children during the 2009-2010 influenza pandemic in the United States. AB - BACKGROUND: The 2009 pandemic influenza A (H1N1) (pH1N1) virus continues to circulate worldwide. Determining the roles of chronic conditions and bacterial coinfection in mortality is difficult because of the limited data for children with pH1N1-related critical illness. METHODS: We identified children (<21 years old) with confirmed or probable pH1N1 admitted to 35 US PICUs from April 15, 2009, through April 15, 2010. We collected data on demographics, baseline health, laboratory results, treatments, and outcomes. RESULTS: Of 838 children with pH1N1 admitted to a PICU, the median age was 6 years, 58% were male, 70% had >=1 chronic health condition, and 88.2% received oseltamivir (5.8% started before PICU admission). Most patients had respiratory failure with 564 (67.3%) receiving mechanical ventilation; 162 (19.3%) received vasopressors, and 75 (8.9%) died. Overall, 71 (8.5%) of the patients had a presumed diagnosis of early (within 72 hours after PICU admission) Staphylococcus aureus coinfection of the lung with 48% methicillin-resistant S aureus (MRSA). In multivariable analyses, preexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among 251 previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8 [95% confidence interval: 3.1-20.6]; P < .0001) remained a mortality risk factor. CONCLUSIONS: Children with preexisting neurologic conditions and immune compromise were at increased risk of pH1N1-associated death after PICU admission. Secondary complications of pH1N1, including myocarditis, encephalitis, and clinical diagnosis of early presumed MRSA coinfection of the lung, were mortality risk factors. PMID- 22065264 TI - Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. AB - Standard pharmacologic closure of the patent ductus arteriosus currently involves the administration of 1 of 2 cyclooxygenase inhibitors: either indomethacin or ibuprofen. However, both of these drugs can be associated with potentially significant adverse effects. We present here the cases of 5 preterm infants (gestational age: 26-32 weeks; postnatal age: 3-35 days) with large, hemodynamically significant patent ductus arteriosus who had either failed or had contraindications to ibuprofen therapy. Each of these infants was treated with off-label oral paracetamol (15 mg/kg per dose every 6 hours). Ductal closure was achieved within 48 hours in all the treated infants. No toxicity was observed. PMID- 22065265 TI - Parent participation and physician-parent communication during informed consent in child leukemia. AB - OBJECTIVE: In this study we evaluated the effectiveness of a physician-directed intervention at enhancing positive physician behaviors and communication strategies during informed consent conferences (ICCs) for pediatric acute leukemia clinical trials. PATIENTS AND METHODS: Physicians at 2 large pediatric hospitals were recruited to participate in a physician-directed intervention (PDI), which included 1 full-day seminar and successive half-day booster sessions. ICCs were then observed, audiotaped, coded, and analyzed to evaluate the effectiveness of the intervention. Data also were collected at 2 control sites. Between 2003 and 2007, 59 ICCs were observed and analyzed. RESULTS: Significant group differences were found in physician rapport-building behaviors. Physicians in the PDI + booster session group engaged in greater rapport-building than did physicians in the PDI group who did not attend booster sessions and physicians in the control group. No group differences were detected for physician partnership-building. In addition, parents in the PDI + booster session group engaged in more general communication and study-related communication, and mothers in the PDI groups asked significantly more questions per minute than did mothers in the control group. CONCLUSIONS: These results provide support for the effectiveness of the PDI at enhancing positive physician behaviors. Booster session attendance is a critical component of physician-directed interventions to improve parental participation and physician-parent communication during ICCs. PMID- 22065266 TI - Limits of human viability in the United States: a medicolegal review. PMID- 22065267 TI - Undernutrition, poor feeding practices, and low coverage of key nutrition interventions. AB - OBJECTIVE: To estimate the global burden of malnutrition and highlight data on child feeding practices and coverage of key nutrition interventions. METHODS: Linear mixed-effects modeling was used to estimate prevalence rates and numbers of underweight and stunted children according to United Nations region from 1990 to 2010 by using surveys from 147 countries. Indicators of infant and young child feeding practices and intervention coverage were calculated from Demographic and Health Survey data from 46 developing countries between 2002 and 2008. RESULTS: In 2010, globally, an estimated 27% (171 million) of children younger than 5 years were stunted and 16% (104 million) were underweight. Africa and Asia have more severe burdens of undernutrition, but the problem persists in some Latin American countries. Few children in the developing world benefit from optimal breastfeeding and complementary feeding practices. Fewer than half of infants were put to the breast within 1 hour of birth, and 36% of infants younger than 6 months were exclusively breastfed. Fewer than one-third of 6- to 23-month-old children met the minimum criteria for dietary diversity, and only ~50% received the minimum number of meals. Although effective health-sector-based interventions for tackling childhood undernutrition are known, intervention-coverage data are available for only a small proportion of them and reveal mostly low coverage. CONCLUSIONS: Undernutrition continues to be high and progress toward reaching Millennium Development Goal 1 has been slow. Previously unrecognized extremely poor breastfeeding and complementary feeding practices and lack of comprehensive data on intervention coverage require urgent action to improve child nutrition. PMID- 22065268 TI - Cobalamin F disease detected by newborn screening and follow-up on a 14-year-old patient. AB - The cobalamin F (cblF) defect is caused by disturbed lysosomal release of cobalamin (vitamin B(12)) into the cytoplasm caused by mutations in the LMBRD1 gene. We present the clinical and biochemical characterization of a patient with newly diagnosed cblF disease and a follow-up on a 14-year-old patient. The new patient presented with elevation of propionyl carnitine found on a newborn screen. The patient was small for gestational age, exhibited dysmorphic features and mild developmental delay, and had trigonocephaly and ventricular septal defect. There was biochemical normalization and clinical improvement within 3 weeks of parenteral cobalamin treatment. The other patient presented at 4 weeks of life with failure to thrive and feeding difficulties. She was treated only with monthly cyanocobalamin shots. The patient has never experienced metabolic decompensation. She had short stature and was an average student with no behavioral concerns. Her metabolic derangements normalized after switching to weekly hydroxycobalamin. The available data on 14 patients with confirmed cblF disease suggest variability in age of onset, presenting symptoms, response to treatment, and long-term complications. Common clinical findings include small for gestational age, feeding difficulties, growth failure, and developmental delays. Some patients have congenital heart defects, dysmorphic features, and other congenital anomalies. PMID- 22065269 TI - Effect of antihypotensive treatment on cerebral oxygenation of preterm infants without PDA. AB - BACKGROUND: Preterm infants with hypotension (mean arterial blood pressure [MABP] < gestational age [GA]) are treated with volume expansion and/or dopamine to ensure adequate cerebral perfusion/oxygenation. We used near-infrared spectroscopy to analyze the effects of volume expansion and dopamine on cerebral oxygenation in hypotensive preterm infants without patent ductus arteriosus (PDA). PATIENTS AND METHODS: Among 390 infants, 71 (GA < 32 weeks) were hypotensive and eligible for inclusion. Thirty-three infants received volume expansion only (NaCl 0.9%; 20 mL/kg), and 38 received additional dopamine (5 MUg/kg per minute). Nine and 11 infants initially treated with dopamine subsequently needed 7.5 and 10 MUg/kg per minute, respectively. Seventy-one infants without hypotension were individually matched to serve as controls. MABP, regional cerebral oxygen saturation (rSco(2)), fractional tissue oxygen extraction (cFTOE), and arterial saturation (Sao(2)) were monitored 15 minutes before and 30 and 60 minutes after volume or dopamine and at comparable postnatal ages in controls. RESULTS: No changes in MABP, rSco(2), or cFTOE were found 30 minutes after volume expansion. MABP increased 60 minutes after 5 MUg/kg per minute dopamine (median [range]: 28 [19-32] vs 33 [23-46] mm Hg; P < .001). There was a small increase and decrease, respectively, in rSco(2) (63 [43-84] vs 66 [46 87]%; P < .05) and cFTOE (0.33 [0.14-0.56] vs 0.31 [0.07-0.54]1/1; P < .05). However, no differences were found at any time point between controls and infants treated with volume or additional dopamine (5, 7.5, and 10 MUg/kg per minute) for rSco(2) or cFTOE. CONCLUSIONS: Volume expansion and additional dopamine do not cause any significant change in rSco(2) or cFTOE in hypotensive preterm infants without PDA. We speculate that very preterm infants with hypotension but without signs of a compromised cerebral oxygenation and systemic perfusion might not be in need of antihypotensive therapy. PMID- 22065270 TI - Recent advances in management and treatment of hereditary angioedema. AB - CONTEXT: Hereditary angioedema (HAE) is a rare autosomal-dominant disease characterized by recurrent self-limiting episodes of skin and mucosal edema. Morbidity and mortality are significant, and new and pending therapies are now available to reduce the risk associated with the disease. OBJECTIVE: To update the reader on new advances in HAE to improve patient care. METHODS: We performed a literature search of Ovid, PubMed, and Google to develop this review. Articles that are necessary for the understanding and use of the new therapeutic options for HAE were chosen, and studies of high quality were used to support the use of therapies, and in most cases, results from phase III studies were used. RESULTS: Until recently, therapy for HAE attacks in the United States consisted of symptom relief with narcotics, hydration, and fresh-frozen plasma, which contains active C1 inhibitor. Therapy to prevent HAE attacks has been confined to androgens and, occasionally, antifibrinolytic agents; however, both drug groups have significant adverse effects. The approval of C1-inhibitor concentrate for prevention and acute therapy has improved efficacy and safety. Ecallantide has also been approved for therapy of attacks, and icatibant is expected to be approved in the next few months for attacks. Recombinant C1 inhibitor is presently in phase III studies and should be available for attacks in the near future. CONCLUSION: In this article we review the changing therapeutic options available for patients in 2011 and beyond. PMID- 22065271 TI - Myocardial infarction associated with use of the synthetic cannabinoid K2. AB - Designer drugs have been problematic over the years. Products such as K2 and Spice, which contain synthetic cannabinoids, are marketed as incense and are widely available on the Internet and at various specialty shops. The effects are reported as cannabis-like after smoking them. In addition, use of these synthetic cannabinoids will not appear on a routine urine toxicology screen. Recently, K2 became a popular alternative to marijuana among youths. Health implications of these designer drugs are not completely understood. Little has been reported about the harmful effects of K2. We report here the first (to our knowledge) cases of myocardial infarction (MI) after smoking K2. Three patients presented separately to the emergency department complaining of chest pain within days after the use of K2. Acute MI was diagnosed in each case on the basis of electrocardiogram changes and elevated troponin levels. Coronary angiography was performed, and the results were normal for the first 2 patients. The incidence of ST-elevation MI is low among teenagers, and association with drug use should be suspected. Public education and awareness need to be heightened about the possible health implications of K2. PMID- 22065272 TI - The association of acetaminophen and asthma prevalence and severity. AB - The epidemiologic association between acetaminophen use and asthma prevalence and severity in children and adults is well established. A variety of observations suggest that acetaminophen use has contributed to the recent increase in asthma prevalence in children: (1) the strength of the association; (2) the consistency of the association across age, geography, and culture; (3) the dose-response relationship; (4) the timing of increased acetaminophen use and the asthma epidemic; (5) the relationship between per-capita sales of acetaminophen and asthma prevalence across countries; (6) the results of a double-blind trial of ibuprofen and acetaminophen for treatment of fever in asthmatic children; and (7) the biologically plausible mechanism of glutathione depletion in airway mucosa. Until future studies document the safety of this drug, children with asthma or at risk for asthma should avoid the use of acetaminophen. PMID- 22065273 TI - Paternal depressive symptoms and child behavioral or emotional problems in the United States. AB - BACKGROUND: The negative effects of maternal mental health problems on child health are well documented. In contrast, there is a profound paucity of information about paternal mental health's association with child health. OBJECTIVE: To investigate the association of paternal mental health problems and depressive symptoms and children's emotional or behavioral problems. METHODS: We analyzed Medical Expenditure Panel Survey data, which included a representative sample of US children (N = 21 993) aged 5 to 17 years and their mothers and fathers. The main outcome measure was child emotional or behavioral problems assessed by using the Columbia Impairment Scale. RESULTS: Paternal depressive symptoms, as assessed using the Patient Health Questionnaire-2, and mental health problems, more generally, assessed by using the Short-Form 12 Scale, were independently associated with increased rates of child emotional or behavioral problems even after controlling for numerous potential confounders including maternal depressive symptoms and other mental health problems. The adjusted odds ratio (aOR) for emotional or behavioral problems among children of fathers with depressive symptoms was 1.72 (95% confidence interval [CI]: 1.33-2.23) and the aOR associated with abnormal paternal scores on the mental component scale of the Short-Form 12 was 1.33 (95% CI: 1.10-1.62) for those within 1 SD below average and 1.48 (95% CI: 1.20-1.84) for those >1 SD below average. CONCLUSIONS: To the best of our knowledge, this is the first study to use a representative US sample to demonstrate that living with fathers with depressive symptoms and other mental health problems is independently associated with increased rates of emotional or behavioral problems of children. PMID- 22065274 TI - Tricyclic antidepressant overdose in a toddler treated with intravenous lipid emulsion. AB - We report a case that involves the use of intravenous lipid emulsion as an antidote for a drug overdose involving a 20-month-old girl who had ingested a potentially lethal amount of the tricyclic antidepressant (TCA) dothiepin. The patient's condition continued to deteriorate despite implementation of standard pediatric treatment recommendations for TCA toxicity. Administration of intravenous lipid emulsion in addition to standard therapy (including sodium bicarbonate) and direct-current cardioversion for ventricular arrhythmia led to a successful outcome. The case report is followed by a review of the current evidence underlying this novel therapy and the background on its use. TCA toxicity is addressed specifically. PMID- 22065275 TI - Stress hyperglycemia: a sign of familial diabetes in children. AB - Stress hyperglycemia in children is considered a benign condition that usually does not mandate further investigation. In some clinical settings it might be the first sign of diabetes mellitus (DM). Two unrelated boys, one aged 2 years 7 months and the other aged 5 days, were evaluated in the emergency department for a febrile infection and found to have elevated blood glucose levels (238 and 150 mg/dL [preprandial], respectively). In both cases the elevated hemoglobin A1c levels (6.5% and 6.6%, respectively) combined with a history of gestational DM in the mother and positive family history for DM suggested maturity-onset diabetes of the young. Genetic analysis revealed 2 known heterozygote mutations in the glucokinase gene: c.697T->C p.C233R in the first case and c.616A->C p.T206P in the second case. Our findings suggest that stress hyperglycemia during early childhood in association with a positive family history of DM might be a sign of monogenic diabetes. PMID- 22065276 TI - Intraoperative parathyroid hormone as an indicator for parathyroid gland preservation in thyroid surgery. AB - BACKGROUND: Intra-operative parathyroid hormone (PTH) levels have successfully been used to assess surgical ablation of parathyroid adenomas, the use of this same test to predict preservation of viable gland has not been widely used. AIM: to test the sensitivity and specificity of intraoperative rapid PTH assay test in predicting permanent postoperative hypoparathyroidism, and applicability to guide the search for inadvertently removed parathyroid glands for possible auto transplantation. PATIENTS AND METHODS: 52 patients undergoing total thyroidectomy for non-malignant thyroid diseases were included. Intraoperative rapid PTH assay test was performed. If levels were reduced, or less than 3 parathyroid glands were detected, removed thyroid gland was examined for unintentionally removed parathyroid tissue for possible auto transplantation. RESULTS: There was a strong correlation between intraoperative rapid PTH assays and those taken 24 hours after surgery, 16 out of 52 patients had reduction of the PTH intraoperatively to levels below 25 pg/ml, of them, 11 patients (who had values between 15-24 pg/ml) recovered to normal PTH levels within 4 weeks, while the 5 patients with intraoperative PTH levels below 15 pg/ml failed to regain normal PTH levels up to 12 weeks postoperatively, even in those patients where parathyroid tissue was auto transplantated. The 4 patients who had parathyroid tissue reimplanted intraoperatively restored some of their parathyroid function as indicated by relative rise of their PTH levels, but did not reach even the low normal levels. (ROC) curve for prediction of early hypoparathyroidism using intraoperative rapid PTH assay was statistically highly significant with optimal cutoff value for predicting early hypocalcaemia level <27 pg/ml, (sensitivity 100%, specificity 68.2%). (ROC) curves for predicting permanent hypoparathyroidism using intraoperative rapid PTH assay or standard PTH assay taken 24 hours after surgery were statistically significant with optimal cutoff value PTH level <12 pg/ml on the intraoperative PTH curve or <15 pg/ml on the postoperative PTH curve (sensitivity 100%, specificity 100%). CONCLUSION: Intraoperative PTH assay may allow intraoperative monitoring of parathyroid function, predicting postoperative outcomes, may identify patients at risk of developing postoperative hypoparathyroidism, guiding surgeons to re-examine removed specimens for inadvertently removed parathyroid tissue with possible auto transplantation, or more practically a guide to early replacement therapy to prevent hypocalcaemia, leading to safe and early hospital discharge. Limitations in our study to be reconsidered in further studies, are relative small sample size, inability for randomisation, and the variable values reported for the cut off value of PTH causing hypocalcaemic symptoms needing intervention. PMID- 22065277 TI - Reinvestigation of the low-temperature form of Ag(2)Se (naumannite) based on single-crystal data. AB - The crystal structure of the low-temperature form of synthetic naumannite [disilver(I) selenide], Ag(2)Se, has been reinvestigated based on single-crystal data. In comparison with previous powder diffraction studies, anisotropic displacement parameters are additionally reported. The structure is composed of Se layers and two crystallographically independent Ag atoms. One Ag atom lies close to the Se layer and is surrounded by four Se atoms in a distorted tetra hedral coordination, while the second Ag atom lies between the Se layers and exhibits a [3 + 1] coordination defined by three close Se atoms, forming a trigonal plane, and one remote Se atom. PMID- 22065278 TI - Cloning and characterization of a novel tyrosine ammonia lyase-encoding gene involved in bagremycins biosynthesis in Streptomyces sp. AB - Tyrosine ammonia lyase catalyzes the deamination of L: -tyrosine to trans coumaric acid. A novel tyrosine ammonia lyase-encoding gene, bagA, was cloned and sequenced from bagremycins-producing strain Streptomyces sp. Tu 4128 whose protein product contains a Ala-Ser-Gly segment in the active site. The disruption of the bagA gene abolished trans-coumaric acid and bagremycins production. trans coumaric acid restored the formation of bagremycin A in the mutant, but not bagremycin B. Thus, trans-coumaric acid is a precursor for biosynthesis of bagremycins and the bagA gene codes for tyrosine ammonia lyase to synthesize trans-coumaric acid. This is a novel bacterial tal gene reported in actinomycetes for the second time and for the first time in a Streptomyces sp. PMID- 22065279 TI - H1N1v at a seroepidemiological glance: is the nightmare over? AB - When the second wave of pandemic influenza A H1N1v 2009 (H1N1v) emerged in the winter of 2010/2011, public health authorities were afraid of dangerous implications and severe clinical courses again. As further H1N1v waves might appear, achievement of sufficient herd immunity is a matter of urgency. The objective of this study was to determine the seroprevalence of antibodies against H1N1v by hemagglutination-inhibition test (HI) after the second wave. We compared our recent findings with our data obtained after the first pandemic in 2009/2010. Between March and May 2011 we collected serum samples from 600 persons aged 1 to 84 years admitted to University Hospital Frankfurt/Main and analysed the titres of anti-H1N1v by HI. The overall seroprevalence of anti-H1N1v has risen from 36.9% (95% confidence interval (95%CI), 33-41) in unvaccinated persons after the first wave to 57.3% (95%CI, 53.1-61.2) in vaccinated and unvaccinated. The highest rate of seropositivity was detected in the age group of 10-19 years (66%; 95%CI, 55.8-75.2), whereas the lowest was found in the age group 40-59 years (51%; 95%CI, 40.8-61.1). Although seroprevalence has significantly increased, sufficient herd immunity is still not achieved. Therefore, general vaccination programs have to be propagated continuously by public health authorities. PMID- 22065280 TI - Prevalence and characterisation of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli isolates in healthy volunteers in Tunisia. AB - The objective of this investigation was to analyse the carriage rate of extended spectrum beta-lactamase (ESBL)-producing Escherichia coli in faecal samples of healthy humans in Tunisia and to characterise the recovered isolates. One hundred and fifty samples were inoculated on MacConkey agar plates supplemented with cefotaxime (2 MUg/ml) for ESBL-positive E. coli recovery. The characterisation of ESBL genes and their genetic environments, detection of associated resistance genes, multilocus sequence typing (MLST) and phylogroup typing were performed by polymerase chain reaction (PCR) and sequencing. The presence and characterisation of integrons and virulence factors were studied by PCR and sequencing. ESBL positive E. coli isolates were detected in 11 of 150 faecal samples (7.3%) and one isolate/sample was further characterised. These isolates contained the blaCTX M-1 (ten isolates) and blaTEM-52c genes (one isolate). The ISEcp1 (truncated by IS10 in four strains) and orf477 sequences were found upstream and downstream, respectively, of all bla (CTX-M-1) genes. Seven different sequence types (STs) and three phylogroups were identified among CTX-M-1-producing isolates [ST/phylogroup (number of isolates)]: ST58/B1 (3), ST57/D (2), ST165/A (1), ST155/B1 (1), ST10/A (1), ST398/A (1) and ST48/B1 (1). The TEM-52-producing isolate was typed as ST219 and phylogroup B2. Six ESBL isolates contained class 1 integrons with the gene cassettes dfrA17-aadA5 (five isolates) and dfrA1-aadA1 (one). Healthy humans in the studied country could be a reservoir of CTX-M-1 producing E. coli. PMID- 22065281 TI - The longitudinal association between glycaemic control and health-related quality of life following insulin therapy optimisation in type 2 diabetes patients. A prospective observational study in secondary care. AB - PURPOSE: To test whether improvement in glycosylated haemoglobin (HbA(1c)) as a marker of glycaemic control, following intensifying insulin therapy, is associated with improvements in HRQoL. METHODS: Dutch sub-optimally controlled (HbA(1c) > 7%) type 2 diabetes patients (N = 447, mean age 59 +/- 11) initiated insulin glargine therapy. Data were collected at baseline, 3 and 6 months, and included HbA(1c) and measures of HRQoL: diabetes symptom distress (Diabetes Symptom Checklist-revised; DSC-r), fear of hypoglycaemia (Hypoglycaemia Fear Survey; HFS-w) and emotional well-being (WHO-5 wellbeing index). RESULTS: HbA(1c) decreased from 8.8 +/- 1.4% to 8.0 +/- 1.2% and 7.7 +/- 1.3% at 3 and 6 months follow-up, respectively (P < 0.001), DSC-r score improved from 17.7 +/- 14.7 to 14.3 +/- 13.3 and 13.6 +/- 13.3 (P < 0.001). HFS-w score did not significantly change. WHO-5 score increased from 56 +/- 23 to 62 +/- 23 and 65 +/- 22 P < 0.001). A modest, significant association was found between HbA(1c) and WHO-5 score (B = -1.8, 95% CI: -2.7 to -0.8) and HbA1c and DSC-r score (B = 1.0, 95% CI: 0.4 to 1.6). No such association was found for HFS-w score. CONCLUSIONS: An association between improvement in HbA(1c) by means of optimising insulin therapy and improvement in HRQoL in type 2 diabetes patients has been observed. A weak, yet significant longitudinal association was found between improved HbA(1c) and emotional well-being and diabetes symptom distress. PMID- 22065282 TI - Prevalence of symptoms, with a focus on fatigue, and changes of symptoms over three months in outpatients receiving cancer chemotherapy. AB - QUESTIONS UNDER STUDY: Prevalence of symptoms, with a focus on fatigue, and changes of symptoms were explored over three months in outpatients with lymphoma, lung, breast or colorectal cancer, receiving chemotherapy in the oncology outpatient clinic of a Swiss tertiary care hospital. METHODS: Prospective, descriptive design; symptom prevalence was measured at start of chemotherapy (T1), and one week prior to the third and fourth cycle (T2, T3). Included were patients starting chemotherapy, with expected survival of >3 months, irrespective of stage of disease. The Memorial Symptom Assessment Scale was used to assess 32 symptoms; fatigue was measured with the FACIT-Fatigue Scale (negative scale). Data were analysed using descriptive statistics and random-intercept regression models. RESULTS: 77 patients participated at T1, 58 and 50 at T2 and T3. Patients experienced on average 9.8, 14.4, and 13.7 symptoms, showing a significant increase over time. Lack of energy and feeling drowsy were most frequent. Symptom scores for lack of energy, changes in skin, pain, and feeling drowsy remained >2 over time (scale 0-4, higher scores = more symptoms). Fatigue mean scores were 36.3, 30.2, and 31.3, showing a significant increase of fatigue over time. Individual symptom trajectories varied widely within and among patients. CONCLUSIONS: High symptom prevalence at start of chemotherapy as well as over time and great variability in symptom experience call for an individual, systematic symptom assessment and management that does not focus solely on side effects of therapy but includes disease-related symptoms to achieve satisfactory control of symptoms in outpatients receiving chemotherapy. PMID- 22065283 TI - Isolation of the opdE gene that encodes for a new hydrolase of Enterobacter sp. capable of degrading organophosphorus pesticides. AB - Microbial enzymes that can hydrolyze organophosphorus compounds have been isolated, identified and characterized from different microbial species in order to use them in biodegradation of organophosphorus compounds. We isolated a bacterial strain Cons002 from an agricultural soil bacterial consortium, which can hydrolyze methyl-parathion (MP) and other organophosphate pesticides. HPLC analysis showed that strain Cons002 is capable of degrading pesticides MP, parathion and phorate. Pulsed-field gel electrophoresis and 16S rRNA amplification were performed for strain characterization and identification, respectively, showing that the strain Cons002 is related to the genus Enterobacter sp. which has a single chromosome of 4.6 Mb and has no plasmids. Genomic library was constructed from DNA of Enterobacter sp. Cons002. A gene called opdE (Organophosphate Degradation from Enterobacter) consists of 753 bp and encodes a protein of 25 kDa, which was isolated using activity methods. This gene opdE had no similarity to any genes reported to degrade organophosphates. When kanamycin-resistance cassette was placed in the gene opdE, hydrolase activity was suppressed and Enterobacter sp. Cons002 had no growth with MP as a nutrients source. PMID- 22065286 TI - Effects of dabigatran in vitro on thrombin biomarkers by Calibrated Automated Thrombography in patients after ischemic stroke. AB - Randomized trials suggest superior and safe stroke prevention in patients with atrial fibrillation after anticoagulation with dabigatran (D) at a 150 mg BID as described in the RE-LY prospective randomized open-label trial when compared to warfarin. Thrombin generation (TG) is a cornerstone of coagulation cascade, and represents a critical biomarker of atherothrombosis. We, therefore, sought to define the effect of D in escalating concentrations on the time course of TG using the Calibrated Automated Thrombogram((r)) (CAT) technology in patients after ischemic stroke. Serial plasma samples were obtained from 20 patients with ischemic stroke documented by neuroimaging, who were treated with aspirin for at least 30 days. The impact of 0.1, 0.23, 0.46, 0.69 mM D in platelet-poor plasma (PPP) on TG indices was assessed using fluorogenic substrate CAT device. The following integrated CAT parameters: TGmax, start time (t-start) peak time (t peak), and mean time (t-mean) were calculated for each D dose and compared with those of the vehicle. Preincubation of PPP with D resulted in dose-dependent significant inhibition of most TG indices. The TGmax was gradually reduced from 447 +/- 21 nM at baseline and reach significance for 0.46 mM D (355 +/- 44 nM, P = 0.03); and decreased further at 0.69 mM D to 302 +/- 27 nM (P = 0.01). The t peak has been achieved 2-3 times later than after vehicle already at 0.23 nM D. The t-start was delayed 3-4 fold starting from 0.23 mM concentration of D (P < 0.001 for all), but not different from D 0.1 mM (1.5 vs. 1.6; P = 0.34). The t mean was not significantly affected by D. D in vitro impacts indices of TG predominantly by dose dependent inhibition of endogenous TG, and delayed thrombin production. This preliminary evidence, while intriguing, requires confirmation in post-stroke patients receiving orally dosed D in order to determine whether these findings are clinically relevant. PMID- 22065287 TI - [Clinical and radiological results after operative treatment of mallet fracture using Kirschner wire technique]. AB - BACKGROUND: In our clinic dorsal distal phalanx fractures involving more than 30% of the articulare line in the lateral view are treated operatively using the Kirschner wire technique. Recently conservative treatment of these fractures is more and more recommended. Therefore we investigated in a retrospective study our patients with special regards to complications. PURPOSE: The aim of this study was to evaluate the complications, as well as the clinical and radiological results of patients after operative treatment of dorsal distal phalanx fractures using the Kirschner wire technique. PATIENTS AND METHODS: 43 patients with dorsal intraarticular fractures of the distal phalanx involving at least one third of the articular surface of the distal interphalangeal (DIP) joint were treated between 02/05 and 08/09 using Kirschner wire technique. At a mean follow-up of 28 (8-60, median 24,5) months, 32 patients were evaluated clinically and radiologically as well as with ultrasound. RESULTS: 5 patients developed superficial wound infections and were treated with antibiotics. 2 of these patients needed an early removal of the Kirschner wires. 2 patients showed nail deformity and 2 had an ulnar deviation of the DIP joint. The mean extension lag was 10 degrees (0-30 degrees , median 10 degrees ), the mean flexion lag was 19 degrees (0-60 degrees , median 15 degrees ). 11 patients had a flexion lag of more than 20 degrees . 4 patients had an extension lag of more than 20 degrees . All of these patients showed tendon tears or large lesions by ultrasound. Degenerative changes were noted in radiographs of 15 patients. CONCLUSIONS: Because of unsatisfactory results in 63% (n=20), conservative treatment will be our treatment of choice in the future. Operative treatment will only be done in patients with subluxation of the distal phalanx. PMID- 22065288 TI - 1-(4-Meth-oxy-phen-yl)-2-methyl-1H-indole-3-carbonitrile. AB - In the title compound, C(17)H(14)N(2)O, the dihedral angle between the indole ring system and the benzene ring is 58.41 (4) degrees . The crystal packing features pi-pi stacking [shortest centroid-centroid separation = 3.8040 (9) A] and C-H?pi inter-actions. PMID- 22065289 TI - N-[(E)-3,4-Dimeth-oxy-benzyl-idene]-2,3-dimethyl-aniline. AB - In the title compound, C(17)H(19)NO(2), the aromatic rings are oriented at a dihedral angle of 59.27 (12) degrees . In the crystal, inversion dimers linked by pairs of weak C-H?O inter-actions generate R(2) (2)(12) loops. PMID- 22065290 TI - Adjuvant therapy for HER2+ breast cancer: practice, perception, and toxicity. AB - Multiple adjuvant regimens are used for HER2+ breast cancer, but experience in routine practice is not reported. We evaluated whether oncologists' perceptions of these regimens matches clinical experience. We surveyed Wisconsin medical oncologists throughout the state regarding factors impacting selection of TCH (docetaxel, carboplatin, and trastuzumab) or anthracycline-based therapy. We also reviewed 200 cases of HER2+ breast cancer treated at the University of Wisconsin and the Marshfield Clinic and collected data on patient and tumor characteristics, chemotherapy regimen, and toxicities. Two-thirds of surveyed oncologists prefer anthracycline-based therapy, particularly for node-positive cancers. However, TCH was preferred for early-stage (T1a-bN0) tumors. Half of oncologists use prophylactic G-CSF with TCH. In the 200 cases reviewed at our centers, acute toxicity occurred more frequently with TCH. There were fewer dose modifications or delays for AC-TH (doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab) than TCH (31% vs. 47%, P = 0.07), possibly due to higher use of prophylactic G-CSF with AC-TH (77% vs. 34% with TCH, P < 0.001). Fifteen patients received prophylactic G-CSF during TCH; none developed neutropenic fever. In contrast, 25% developed neutropenic fever during TCH without G-CSF. There were modest declines in median left ventricular ejection fraction reaching 9% with AC TH and 3% with TCH at 12 months, but early cessation of trastuzumab was similar for both regimens. We conclude that TCH and AC-TH are common adjuvant regimens used for HER2+ breast cancer. The preference of TCH for early-stage disease and anthracycline-based therapy for node-positive disease suggests that many oncologists perceive that TCH is safer and AC-TH more effective. Myelosuppression from TCH is greater than AC-TH, but can be mitigated with routine G-CSF. PMID- 22065291 TI - Prognostic role of CA15.3 in 7942 patients with operable breast cancer. AB - To assess the prognostic value of presurgical CA15.3 in a large cohort of patients with early breast cancer. A total of 7.942 consecutive patients with breast cancer operated at the European Institute of Oncology between 1998 and 2005 and with presurgical values of CA 15.3 available were included. We explored patterns of recurrence by baseline CA 15.3 values. Mean CA15.3 was 17.0 U/ml. CA15.3 was associated with age, tumor size, nodal involvement, Ki-67 labeling index, grade, HER2 expression, molecular subtype, and perivascular invasion. CA15.3 was independently associated with distant metastases [HR > 20 U/ml vs. <= 20 U/ml: 1.34 (95% CI 1.15-1.56)] and death [HR > 20 U/ml vs. <= 20 U/ml: 1.30 (95% CI 1.11-1.53)]. When considering CA15.3 as continuous variable, we observed a constant risk of metastasis and death from the lowest values to about 15-20 U/ml, and then a significantly increasing risk with increasing values of CA15.3. Finally, CA15.3 provided significant additional information to the common prognostic factors to predict the occurrence of metastases (C-index P value 0.04). In patients with operable breast cancer, presurgical CA15.3 value is an independent prognostic factor for metastases and deaths. CA15.3 provides additional information to the common prognostic factors and should be considered in the adjuvant therapeutic algorithm. PMID- 22065292 TI - Bis[3,5-difluoro-2-(4-methyl-pyridin-2-yl)phenyl-kappaC,N](picolinato kappaN,O)iridium(III) chloro-form monosolvate. AB - In the title complex, [Ir(C(12)H(8)F(2)N)(2)(C(6)H(4)NO(2))].CHCl(3), two similar mol-ecules of each component comprise the asymmetric unit. The independent complex mol-ecules are linked by inter-molecular pi-pi inter-actions [centroid centroid distance = 3.830 (4) A]. The Ir(III) ion adopts a distorted octa-hedral geometry, being coordinated by three N atoms, two C atoms, and one O atom of three bidentate ligands, with the N atoms arranged meridionally. PMID- 22065293 TI - Patients with focal full-thickness cartilage lesions benefit less from ACL reconstruction at 2-5 years follow-up. AB - PURPOSE: To investigate differences in patient-reported outcome after anterior cruciate ligament (ACL) reconstruction between patients with and without a concomitant full-thickness cartilage lesion. METHODS: 30 primary ACL reconstructed patients with an isolated concomitant full-thickness cartilage lesion and 59 matched controls without cartilage lesions were identified in the Norwegian National Knee Ligament Registry and included in the present study. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used as the outcome measure. At a median follow-up of 2.1 years (range, 2-5 years) after ACL reconstruction, 80 (90%) of the patients completed the KOOS. RESULTS: Preoperatively, there were no differences in KOOS between the study group and the control group. At follow-up, patients with full-thickness cartilage lesions reported significantly decreased scores compared to patients without cartilage lesions in the KOOS subscales pain (mean difference, 8.1; 95% confidence interval [CI], 0.8-15.3), activities in daily living (mean difference, 5.8; 95% CI, 0.3 11.2), sport/recreation (mean difference, 19.8; 95% CI, 5.3-34.3) and quality of life (mean difference, 17.2; 95% CI, 4.2-30.1). Patients with full-thickness cartilage lesions reported significantly less improvement from preoperative to follow-up than patients without cartilage lesions for the KOOS subscales pain (mean difference, 11.6; 95% CI, 3.2-19.9), sport/recreation (mean difference, 20.6; 95% CI, 8.1-33.1) and quality of life (mean difference, 16.3; 95% CI, 3.8 28.7). CONCLUSIONS: ACL-injured patients with full-thickness cartilage lesions reported worse outcomes and less improvement after ACL reconstruction than those without cartilage lesions at 2-5 years follow-up. LEVEL OF EVIDENCE: Prognostic; prospective cohort study, Level I. PMID- 22065294 TI - The effect of tranexamic acid on blood loss and use of blood products in total knee arthroplasty: a meta-analysis. AB - PURPOSE: Studies have shown that tranexamic acid (TXA) reduces blood loss and transfusion need in patients undergoing total knee arthroplasty (TKA). However, no single study has been large enough to definitively determine whether the drug is safe and effective. We report a systematic review and meta-analysis of randomised controlled trials evaluating the efficacy and safety of TXA in reducing blood loss and transfusion in TKA. METHODS: A comprehensive literature search was done in Cochrane Library, MEDLINE, EMBASE, and CNKI. Two reviewers independently identified the eligible studies, assessed their methodological quality, and extracted data. The data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group. The relevant data were analyzed using RevMan 5.0. RESULTS: Fifteen randomized controlled trials involving 842 patients were included. The use of TXA reduced total blood loss by a mean of 487 ml [95% confidence interval (CI) -629 to -344], intra operative blood loss by a mean of 127 ml (95% CI -313-59), and post-operative blood loss by a mean of 245 ml (95% CI -410 to -80). TXA led to a significant reduction in the proportion of patients requiring blood transfusion (risk difference -0.4). There were no significant differences in deep-vein thrombosis (DVT), pulmonary embolism, or other complications among the study groups. CONCLUSION: Meta-analysis indicates that TXA may reduce post-operative, total blood loss and transfusion in patients undergoing TKA. TXA led to a significant reduction in the proportion of patients requiring blood transfusion. LEVEL OF EVIDENCE: Therapeutic study (Systematic review of Level I studies with inconsistent results), Level II. PMID- 22065295 TI - Short-term outcome of the second generation characterized chondrocyte implantation for the treatment of cartilage lesions in the knee. AB - PURPOSE: To evaluate short-term clinical and MRI outcome of the second generation characterized chondrocyte implantation (CCI) for the treatment of cartilage defects in the knee. METHODS: Thirty-two patients aged 15-51 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of different locations in the knee were treated with CCI using a synthetic collagen I/III membrane to cover the defect. Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) for pain. Serial magnetic resonance imaging (MRI) scans of 22 patients were scored using the original and modified Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system. RESULTS: The patients included in this study showed a significant gradual clinical improvement after CCI. The MRI findings of this pilot study were considered to be promising. No signs of deterioration were observed. A complete or hypertrophic filling was observed in 76.5% of the cases at 24 months of follow up. No preventive effect of an avital membrane on the occurrence of hypertrophic repair tissue was observed on MRI. Three failures were observed among the 32 patients until now (9.4%). CONCLUSIONS: This investigation provided useful information on the efficacy of this treatment. The short-term clinical and MRI outcome are promising. Large-scale and long-term trials are mandatory to confirm the results and the reliability of this procedure. LEVEL OF EVIDENCE: IV. PMID- 22065296 TI - The New Walter Reed National Military Medical Center. PMID- 22065297 TI - Support for women in osteopathic medicine who breastfeed: a call for action. PMID- 22065298 TI - Developmental and persistent developmental stuttering: an overview for primary care physicians. AB - Stuttering is a speech disorder characterized by a disruption in the fluency, timing, and rhythm of normal speech. It affects approximately 5% of children at some point in their lives. Although dysfluency often resolves before adulthood, it may cause periods of extreme anxiety for patients, especially those who continue to stutter in adolescence and adulthood. Although these patients are unlikely to stop stuttering, treatment options are available to reduce anxiety and therefore the severity of symptoms. In the present review article, the authors discuss the pathophysiology, diagnosis, and management of developmental stuttering in children and adults. PMID- 22065299 TI - Osteopathic distinctiveness in osteopathic predoctoral education and its effect on osteopathic graduate medical education. AB - The number of colleges of osteopathic medicine (COMs), osteopathic medical students, and osteopathic physicians in practice has been consistently growing since the 1960s. In recent years, the growth of the profession has been exponential. Despite this growth, graduates of COMs are increasingly choosing allopathic residencies. The authors believe that this trend may stem from a lack of focus on osteopathic principles and practice in COMs, as well as geographic and specialty limitations of available osteopathic residency positions. The present article will briefly examine the history of AOA accreditation and the current accreditation process and the current state of osteopathic predoctoral education and postdoctoral training. The authors call on osteopathic physicians to help bring osteopathic distinctiveness to osteopathic predoctoral education by mentoring and volunteering at COMs. In addition, the authors urge the osteopathic profession to increase the number of osteopathic residencies to account for the number of and distribution of osteopathic medical school graduates. PMID- 22065300 TI - Sacral stress fracture in a distance runner. AB - Sacral stress fractures are uncommon injuries that are associated with repetitive load-bearing activities. The authors describe a 23-year-old male cross-country runner who presented with low back and buttocks pain. Radiographic findings were unremarkable, but a hop test identified a sacral stress fracture. The patient was instructed to stop running and to take calcium and vitamin D supplements. Four months later, his symptoms completely resolved and he began running again. The authors also present a review of the literature, which revealed that patients with sacral stress fractures are likely to have normal neurologic examinations and full active range of motions. However, they will likely describe discomfort with passive hip flexion. The authors recommend the hop test for patients with this type of history and these physical examination findings. If a sacral stress fracture is found, treatment regimens should consist of 4 to 6 weeks of rest with gradual return to activity. PMID- 22065301 TI - A safe and effective plant gene switch system for tissue-specific induction of gene expression in Arabidopsis thaliana and Brassica juncea. AB - The ability to regulate spatial and temporal expression of genes is a useful tool in biotechnology as well as studies of functional genomics. Such regulation can provide information concerning the function of a gene in a developmental context while avoiding potential harmful effects due to constitutive overexpression of the gene. A GUS gene construct that uses the ecdysone receptor-based chemically inducible system and several different tissue-specific promoters was introduced into the model plant Arabidopsis thaliana and into the crop plant Brassica juncea. Here we describe the results of studies showing that this system provides both temporal and spatial control of transgene expression, and confirm that this system is useful for tissue-specific and temporal induction of gene expression in A. thaliana and B. juncea. PMID- 22065302 TI - Non-occupational sitting and mental well-being in employed adults. AB - BACKGROUND: Emerging evidence suggests that sedentary behaviour may be adversely associated with physical health, but few studies have examined the association with mental well-being. PURPOSE: This study examined the association of four non occupational sedentary behaviours, individually and in total, with mental well being in employed adults. METHODS: Baseline data from the evaluation of Well@Work, a national workplace health promotion project conducted in the UK, were used. Participants self-reported sitting time whilst watching television, using a computer, socialising and travelling by motorised transport. Mental well being was assessed by the 12-item version of the general health questionnaire. Analyses were conducted using multiple linear regression. RESULTS: In models adjusted for multiple confounders, TV viewing, computer use and total non occupational sitting time were adversely associated with general health questionnaire-12 assessed mental well-being in women. Computer use only was found to be adversely associated with mental well-being in men. CONCLUSION: Sedentary behaviour may be adversely associated with mental well-being in employed adults. The association may be moderated by gender. PMID- 22065303 TI - Progress of the Asian Society of Cardiovascular Imaging. AB - ASCI has continued to grow over the past 5 years since its establishment in 2006. Recent record shows total membership of 804 from 34 countries and 1,032 attendants from 32 countries at the last annual congress in Hong Kong in 2011. ASCI publishes ASCI Special Issues twice a year in the International Journal of Cardiovascular Imaging. The Asian CCT and CMR Guideline Working Group of ASCI published guidelines and protocol in the ASCI Special Issue of the International Journal of Cardiovascular Imaging in 2010. ASCI launched the [ASCI](2) (Advanced School for Core Investigators from ASCI) Program with the aim to recruit young ASCI members of high potential and train them to become representative scholars of Asia, which was met with much success in 2010 and 2011. ASCI is trying to widen its scope by collaborating with other cardiovascular imaging societies including the European Society of Cardiovascular Radiology. Multicenter trials by ASCI researchers and cardiac imaging registry in the Asian population are being designed to represent ASCI. PMID- 22065304 TI - Differing perceptions of intervention thresholds for fracture risk: a survey of patients and doctors. AB - This survey suggests that patients are prepared to accept higher absolute fracture risk than doctors, before considering pharmacological therapy to be justified. Patients require that drug treatments confer substantial fracture risk reductions in order to consider long-term therapy. INTRODUCTION: Absolute fracture risk estimates are now incorporated into osteoporosis treatment guidelines. At present, little is known about how patients regard fracture risk and its management. We set out to describe and compare the views of patients and doctors on the level of fracture risk at which drug treatment is justified. METHODS: A cross-sectional survey was conducted on 114 patients referred for bone density measurement and 161 doctors whose practice includes management of osteoporosis. Participants were asked about fracture risk thresholds for pharmacological intervention. RESULTS: The absolute risk of both major osteoporotic fracture and hip fracture at which drug treatment was considered by patients to be justifiable was higher than that reported by doctors [major osteoporotic fracture, median (interquartile range): patients, 50% (25 to 60); doctors, 10% (10 to 20); P < 0.0001; hip fracture: patients, 50% (25 to 60); doctors, 10% (5 to 20); P < 0.0001]. Patients required that a drug provide a median 50% reduction in relative risk of fracture in order to consider taking long-term therapy, irrespective of the treatment mode or dosing schedule. Among doctors, there was an inverse relationship between the number of osteoporosis consultations conducted each month and threshold of risk for recommending drug treatment (r = -0.22 and r = -0.29 for major osteoporotic fracture and hip fracture, respectively, P < 0.01 for both) CONCLUSIONS: Patients are prepared to accept higher absolute fracture risk than doctors, before considering pharmacological therapy to be justified. Patients require that drug treatments confer substantial fracture risk reductions in order to consider long-term therapy. PMID- 22065305 TI - Reproductive performance in out-of-breeding season of fatty ewes using implant norgestomet with or without PMSG. AB - Pregnancy in out-of-breeding season in ewes increases the economical goals. Synchronization of estrus and ovulation is essential for above program. The aims of this study using implant norgestomet with or without Pregnant Mare Serum Gonadotropin (PMSG) were to evaluate the serum progesterone (P4) concentration changes: the conception rate and estimation of the lambing rate and litter size. In total, 80 non-cycling multiparous Iranian Kurdish breed fat-tailed ewes with <0/5 ng/ml P4 were used in April and May 2008 in the suburb of Mashhad, Iran. The animals were randomly divided into three groups: a control group (n = 30) without hormonal treatment, another group (n = 25) received 3 mg of norgestomet implant placed subcutaneously in the convex surface of the ear for 9 days, and the third group (n = 25) treated with 3 mg of norgestomet implant for 9 days with an IM injection of 500 IU PMSG at implant removal. The progesterone of treatment and control groups were measured on days 4, 9, and 13 after removal of the norgestomet using radioimmunoassay. Every five ewes were exposed to one ram after 24 h of norgestomet removal in treatment and control groups, simultaneously. The pregnancy was examined after 25 days of ram removal using ultrasonography. Progesterone concentration was significantly higher in treatment groups on 9 and 13 days after norgestomet removal (P < 0.05). The pregnancy rate in the control, non-PMSG, and PMSG treatments groups were 17%, 52%, and 72%, respectively. The rates of single and twin pregnancy in the non-PMSG treatment group were 69% and 31%, respectively. These rates in norgestomet and PMSG treatment group were 50% and 39%, respectively. Triplet pregnancy (11%) was observed only in the PMSG treatment group. It was concluded that using implant norgestomet especially accompanied with PMSG can increase and improve the fertilization rate of ewe in the out-of-breeding season program. PMID- 22065306 TI - Maedi-visna virus infection in Karayaka and Amasya Herik breed sheep from provinces in northern Turkey. AB - Maedi-visna is an important virus infection of sheep having prolonged incubation period (slow disease) and reflecting two distinct forms clinically and pathologically. In this study, the presence of MVV was investigated serologically in 58 Amasya Herik sheep breed and 525 Karayaka sheep breed. Seropositivity rates in Amasya Herik sheep breed and Karayaka sheep breed were detected as 69.0% and 18.5%, respectively. MVV antibodies were found in 137 of 583 serum samples (23.5%). Positivity rates for the provinces varied and were as follows: Samsun 19.4%, Sinop 15.4%, Ordu 25.8%, Trabzon 26.7%, Rize 36.7%, Amasya 69.0% and Tokat 35.0%, however no antibody response was detected in all of the sheep in Giresun province. PMID- 22065307 TI - Presence of an interaction between smoking and being overweight increases risks of hypertension, diabetes, and cardiovascular disease in outpatients with mood disorders. AB - OBJECTIVE: We aimed to evaluate the hypothesis that the presence of an interaction between smoking and being overweight increases the risks of lifestyle related diseases (hypertension, diabetes mellitus, dyslipidemia, and cardiovascular disease) in outpatients with mood disorders. METHODS: In this cross-sectional survey, using data from 213 outpatients with mood disorders (95 men, 118 women), we calculated the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for each of hypertension, diabetes, dyslipedemia, and cardiovascular disease, using a binary logistic regression model; we then calculated the adjusted OR values for smokers and non-smokers with body mass indexes (BMIs) of <25 or >=25 kg/m2. Next, we examined the data for the presence of an interaction between smoking and being overweight, using three measures of additive interaction: relative excess risk due to the interaction (RERI), attributable proportion due to the interaction (AP), and the synergy index (S). RESULTS: Smokers with BMI <25 kg/m2 had a significantly lower risk of hypertension (OR 0.27, 95% CI 0.09-0.81) than non-smokers with BMI <25 kg/m2 (reference group). Compared with the reference group, overweight non-smokers had a significantly higher risk (2.82, 1.34-6.19) of hypertension, and overweight smokers had a higher risk (4.43, 1.28-15.26) of hypertension and very high risks of diabetes (8.24, 2.47-27.42) and cardiovascular disease (13.12, 1.95-88.41). The highest RERI was derived from the relation with cardiovascular disease. The highest AP and S were derived from the relation with type 2 diabetes. There was no interaction of smoking and being overweight with dyslipidemia. CONCLUSION: The presence of an interaction between smoking and being overweight exacerbates the risks of hypertension, diabetes, and cardiovascular disease in outpatients with mood disorders. PMID- 22065308 TI - The chemical compound PTC124 does not affect cellular electrophysiology of cardiac ventricular myocytes. AB - PURPOSE: Nonsense mutations that create premature termination codons (PTC) leading to disease by a mechanism of haploinsufficiency are relatively common in the SCN5A gene encoding the major sodium channel in heart. PTCs in SCN5A are associated with isolated conduction disease and Brugada syndrome (BrS). Pharmacological therapy does not exist for these disorders, but would be highly beneficial. Recently, an orally bio-available drug capable of suppressing premature termination, PTC124, has been identified that selectively induces ribosomal read-through of premature but not normal termination codons. In this study, we tested the acute and long-term effects of PTC124 on action potential characteristics of rabbit ventricular cardiomyocytes. METHODS: The effects of PTC124 on action potentials of isolated adult rabbit ventricular cardiomyocytes were studied using the perforated patch-clamp methodology. Acute effects of PTC124 were measured in freshly isolated cardiomyocytes, while long term effects were measured after 48 h in cultured cardiomyocytes. RESULTS: Resting membrane potential, maximum upstroke velocity, action potential amplitude and action potential duration at 20, 50 and 90% of repolarization were not affected by application of PTC124, neither acute nor after 48 h. CONCLUSION: PTC124 has no acute or long-term effects on rabbit ventricular action potentials. These experiments form the basis for future studies evaluating the use of this therapy in preventing potentially lethal arrhythmias in patients with BrS and/or conduction disease. PMID- 22065309 TI - Erratum: 2-Benz-yloxy-1,2,4-triazolo[1,5-a]quinazolin-5(4H)-one. Corrigendum. AB - The name of one of the authors in the paper by Al-Salahi et al. [Acta Cryst. (2011), E67, o1861] is corrected.[This corrects the article DOI: 10.1107/S1600536811024962.]. PMID- 22065310 TI - (R)-2-Phen-oxy-1-(4-phenyl-2-sulfan-ylidene-1,3-oxazolidin-3-yl)ethanone. AB - The central 1,3-oxazolidine-2-thione ring in the title compound, C(17)H(15)NO(3)S, is approximately planar with maximum deviations of 0.036 (4) and -0.041 (5) A for the O and methyl-ene-C atoms, respectively. The dihedral angles formed between this plane and the two benzene rings, which lie to the same side of the central plane, are 86.5 (2) [ring-bound benzene] and 50.6 (3) degrees . The ethan-1-one residue is also twisted out of the central plane, forming a O-C N-C torsion angle of 151.5 (5) degrees . The dihedral angle formed by the benzene rings is 62.8 (2) degrees so that overall, the mol-ecule has a twisted U-shape. In the crystal, mol-ecules are linked into supra-molecular arrays two mol-ecules thick in the bc plane through C-H?O, C-H?S and C-H?pi inter-actions. PMID- 22065311 TI - Rhizobium helanshanense sp. nov., a bacterium that nodulates Sphaerophysa salsula (Pall.) DC. in China. AB - Studying rhizobia in the root nodules of Sphaerophysa salsula (Pall.) DC in the northwest of China, we obtained five strains classified as genus Rhizobium on the basis of their 16S rRNA gene sequences. The sequence similarity of strain CCNWQTX14(T) with the most related species was 99.0%. Further phylogenetic analysis of housekeeping genes (recA and atpD) suggested the five strains comprised a novel lineage within Rhizobium. The nifH and nodD gene sequences of CCNWQTX14(T) were phylogenetically closely related with those of Sinorhizobium kummerowiae and R. sphaerophysae, respectively. The five strains isolated from different places were also distinct from related Rhizobium species using ERIC fingerprint profiles. The DNA-DNA hybridization value was 41.8% between CCNWQTX14(T) and Rhizobium sphaerophysae CCNWGS0238(T). Our novel strains were only able to form effective nodules on its original host Sphaerophysa salsula. Our data showed that the five Rhizobium strains formed a unique genomic species, for which a novel species Rhizobium helanshanense sp. nov. is proposed. The type strain is CCNWQTX14(T) (=ACCC 16237(T) =HAMBI 3083(T)). PMID- 22065312 TI - Update--Ethical standards in sport and exercise science research. PMID- 22065313 TI - A 'new' method to normalize exercise intensity. PMID- 22065314 TI - Happy Mother's Day. PMID- 22065315 TI - Integration of 3D volumetry, portal vein transection and in situ split procedure: a new surgical strategy for inoperable liver metastasis. AB - INTRODUCTION: The purpose of this study was to report on the feasibility of integrating 3D preoperative volumetry, portal vein transection and in situ split procedure. A 54-year-old female with now resectable colorectal liver metastasis (CRLM) (segments III, IVb, V-VIII) underwent a two-staged procedure. METHODS: Segment III resection, right portal vein transection and an in situ split procedure (first stage) after 3D volumetry based on CT data and a right trisegmentectomy (second stage) were performed. RO resection of metastases was achieved, and the postoperative course was uneventful. CONCLUSION: The proposed strategy seems to be a promising method to achieve higher resectability rates in CRLM patients. PMID- 22065316 TI - Molecular mechanism underlying the detection of colorectal cancer by 18F-2-fluoro 2-deoxy-D-glucose positron emission tomography. AB - BACKGROUND: Biological imaging by positron emission tomography (PET) using 18F-2 fluoro-2-deoxy-D-glucose (FDG) has been widely used clinically for the detection of primary tumors and for early prediction of response to chemotherapy. In this study, we examined the molecular mechanism underlying the detection of colorectal cancers by FDG-PET. MATERIAL AND METHODS: In all, 37 patients with colorectal cancer were examined with FDG-PET, and the maximal standardized uptake value (SUV) was calculated. Using surgical tissue samples, we examined the expression levels of hypoxia-inducible factor alpha (HIF1alpha), a marker of tissue hypoxia; proliferative cellular nuclear antigen (PCNA), a marker of proliferation; and glucose transporter (GLUT)1 and hexokinase (HK)2, protein of glucose uptake by using reverse transcriptase-polymerase chain reaction. RESULTS: All except two colorectal cancer lesions showed increased uptake of FDG. The mean SUV of FDG-PET was 12.0 +/- 1.2 (+/-SEM). The mean mRNA expression levels of GLUT1 and HK2 were significantly higher in cancer tissues than in the surrounding normal mucosa. Moreover, to promote the upregulation of glucose uptake, the expressions of HIF1alpha and PCNA were induced to 2.6 and 3.3 times higher than that in the normal mucosa. However, the quantitative correlation analysis showed SUV was correlated with HIF1alpha expression but not with PCNA expression. CONCLUSION: Our molecular-based analysis suggested that FDG accumulation due to induction of glucose uptake proteins might be associated with the hypoxic environment in tumors rather than the tumor growth. Therefore, for assessing the efficacy of chemotherapy using FDG-PET, we must keep in mind that SUV does not indicate the tumor growth directly. PMID- 22065317 TI - Budd-Chiari syndrome revisited: 38 years' experience with surgical portal decompression. AB - OBJECTIVE: Ten years ago, we reported our results with what remains as the largest clinical experience with surgical portal decompression for Budd-Chiari syndrome (BCS) in the West. Since then, our series has expanded to 77 patients, and there has been an explosion of interest in and publications about BCS. The objectives of this study are to assess the validity of our observations and conclusions regarding BCS reported 10 years ago by expansion of our series of patients and observations of outcomes over an additional decade of close follow up. METHODS: Seventy-seven patients with BCS were allocated to three groups: group I, 39 had hepatic vein occlusion alone, treated by side-to-side portacaval shunt (SSPCS); group II, 26 had inferior vena cava occlusion treated by mesoatrial shunt in eight and combined SSPCS and cavoatrial shunt (CAS) in 18; and group III, 12 had decompensated cirrhosis too late for portal decompression who were listed for liver transplantation (LT). An extensive diagnostic workup included angiography with pressure measurements and needle liver biopsy. Follow up was 100%, lasting 5-38 years. RESULTS: In group I, long-term survival is 95% with 36 free of ascites, leading lives of good quality 5-38 years post-SSPCS. In group II, mesoatrial shunt was discontinued after 1990 because of a high failure rate, but combined SSPCS-CAS has resulted in 100% survival for 5-25 years. In group III, six patients (50%) are alive and well for more than 5 years post-LT. Serial liver biopsies following portal decompression have shown long-term reversal of the lesions of BCS. CONCLUSIONS: Long-term survival following portal decompression of BCS in the West has not been equaled by any other form of therapy, medical or surgical. It is imperative to perform surgical portal decompression early in the course of BCS in order to avoid irreversible liver damage. PMID- 22065318 TI - Effect of neoadjuvant chemoradiation and surgical technique on recurrence of localized pancreatic cancer. AB - OBJECTIVES: To determine the influence of neoadjuvant chemoradiation and standardized dissection of the superior mesenteric artery upon the oncologic outcome of patients with localized pancreatic adenocarcinoma. METHODS: One hundred ninety-four patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy between 2004 and 2008 were evaluated. The retroperitoneal dissection was performed directly along the superior mesenteric artery in all cases. A standard histopathologic protocol that measured the "superior mesenteric artery (SMA) margin distance" between cancer cells and the superior mesenteric artery was employed. RESULTS: Seventy-six percent of patients received neoadjuvant chemoradiation. The SMA margin was positive in 4% of patients but an additional 22% of patients with a negative margin had a SMA margin distance of <=1 mm. Preoperative CT images overestimated the SMA margin distance in 73% of cases. Patients who received chemoradiation had longer SMA margin distances than those who did not. Patients who received chemoradiation and had a SMA margin of >1 mm had the lowest recurrence rates. Administration of neoadjuvant chemoradiation and lower estimated blood loss were independently associated with longer progression-free survival on multivariate analysis. CONCLUSIONS: Preoperative chemoradiation and meticulous dissection of the superior mesenteric artery maximize the distance between cancer cells and the SMA margin and may influence locoregional control. PMID- 22065319 TI - A root-cause analysis of mortality following major pancreatectomy. AB - INTRODUCTION: Although mortality rates from pancreatectomy have decreased worldwide, death remains an infrequent but profound event at an individual practice level. Root-cause analysis is a retrospective method commonly employed to understand adverse events. We evaluate whether emerging mortality risk assessment tools sufficiently predict and account for actual clinical events that are often identified by root-cause analysis. METHODS: We assembled a Pancreatic Surgery Mortality Study Group comprised of 36 pancreatic surgeons from 15 institutions in 4 countries. Mortalities after pancreatectomy (30 and 90 days) were accrued from 2000 to 2010. For root-cause analysis, each surgeon "deconstructed" the clinical events preceding a death to determine cause. We next tested whether mortality risk assessment tools (ASA, POSSUM, Charlson, SOAR, and NSQIP) could predict those patients who would die (n = 218) and compared their prognostic accuracy against a cohort of resections in which no patient died (n = 1,177). RESULTS: Two hundred eighteen deaths (184 Whipple's resection, 18 distal pancreatectomies, and 16 total pancreatectomies) were identified from 11,559 pancreatectomies performed by surgeons whose experience averaged 14.5 years. Overall 30- and 90-day mortalities were 0.96% and 1.89%, respectively. Individual surgeon rates ranged from 0% to 4.7%. Only 5 patients died intraoperatively, while the other 213 succumbed at a median of 29 days. Mean patient age was 70 years old (38% were >75 years old). Malignancy was the indication in 90% of cases, mostly pancreatic cancer (57%). Median operative time was 365 min and estimated blood loss was 700 cc (range, 100-16,000 cc). Vascular repair or multivisceral resections were required for 19.7% and 15.1%, respectively. Seventy seven percent had a variety of major complications before death. Eighty-seven percent required intensive care unit care, 55% were transfused, and 35% were reoperated upon. Fifty percent died during the index admission, while another 11% died after a readmission. Almost half (n = 107) expired between 31 and 90 days. Only 11% had autopsies. Operation-related complications contributed to 40% of deaths, with pancreatic fistula being the most evident (14%). Technical errors (21%) and poor patient selection (15%) were cited by surgeons. Of deaths, 5.5% had associated cancer progression-all occurring between 31 and 90 days. Even after root-cause scrutiny, the ultimate cause of death could not be determined for a quarter of the patients-most often between 31 and 90 days. While assorted risk models predicted mortality with variable discrimination from nonmortalities, they consistently underestimated the actual mortality events we report. CONCLUSION: Root-cause analysis suggests that risk prediction should include, if not emphasize, operative factors related to pancreatectomy. While risk models can distinguish between mortalities and nonmortalities in a collective fashion, they vastly miscalculate the actual chance of death on an individual basis. This study reveals the contributions of both comorbidities and aggressive surgical decisions to mortality. PMID- 22065320 TI - Pulmonary hypertension, how to diagnose and who to treat? PMID- 22065321 TI - BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity. AB - MT1-MMP (membrane type 1-matrix metalloproteinase) plays important roles in cell growth and tumor invasion via mediating cleavage of MMP2/gelatinase A and a variety of substrates including type I collagen. BST-2 (bone marrow stromal cell antigen 2) is a membrane tetherin whose expression dramatically reduces the release of a broad range of enveloped viruses including HIV from infected cells. In this study, we provided evidence that both transient and IFN-alpha induced BST 2 could decrease the activity of MMP2 via binding to cellular MT1-MMP on its C terminus and inhibiting its proteolytic activity; and finally block cell growth and migration. Zymography gel and Western blot experiments demonstrated that BST 2 decreased MMP2 activity, but no effect on the expression of MMP2 and MT1-MMP genes. Confocal and immunoprecipitation data showed that BST-2 co-localized and interacted with MT1-MMP. This interaction inhibited the proteolytic enzyme activity of MT1-MMP, and blocked the activation of proMMP2. Experimental results of C-terminus deletion mutant of MT1-MMP showed that activity of MMP2 was no change and also no interaction existed between the mutant and BST-2 after co transfection with the mutant and BST-2. It meant that C-terminus of MT1-MMP played a key role in the interaction with BST-2. In addition, cell growth in 3D type I collagen gel lattice and cell migration were all inhibited by BST-2. Taken together, BST-2, as a membrane protein and a tetherin of enveloped viruses, was a novel inhibitor of MT1-MMP and could be considerable as an inhibitor of cancer cell growth and migration on clinic. PMID- 22065323 TI - An international perspective on abnormal uterine bleeding. PMID- 22065324 TI - A five-year international review process concerning terminologies, definitions, and related issues around abnormal uterine bleeding. AB - Over the past decade there has been an increasing realization about the extent of confusion associated with the many terminologies used to describe abnormal uterine bleeding (AUB). This led to the organization of an international workshop of 35 experts from 15 countries in Washington, D.C., USA, in 2005, which addressed the confusions and controversies around AUB. The workshop comprehensively addressed anomalies in the terminologies, definitions, and causes of AUB. It also began to address broader issues including investigations, quality of life, the need for structured symptom questionnaires, cultural aspects, and future research needs. This workshop led to a series of recommendations and publications and to the establishment of the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Working Group. Since then, a series of international presentations and small group workshops has resulted in a wide awareness of the program and a comprehensive series of recommendations and publications. A particularly influential large-scale interactive workshop with 600 attendees was held during the 2009 FIGO World Congress, which demonstrated the broad acceptability of the current recommendations. This article describes the process leading to the development of international recommendations on terminologies, definitions, and classification of causes of AUB and the establishment of the FIGO Menstrual Disorders Working Group. PMID- 22065325 TI - The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. AB - Over the past 5 years there has been a major international discussion aimed at reaching agreement on the use of well-defined terminologies to describe the normal limits and range of abnormalities related to patterns of uterine bleeding. This article builds on concepts previously presented, which include the abandonment of long-used, ill-defined, and confusing English-language terms of Latin and Greek origin, such as menorrhagia and metrorrhagia. The term DYSFUNCTIONAL UTERINE BLEEDING should also be discarded. Alternative terms and concepts have been proposed and defined. The terminologies and definitions described here have been comprehensively reviewed and have received wide acceptance as a basis both for routine clinical practice and for comparative research studies. It is anticipated that these terminologies and definitions will be reviewed again on a regular basis through the International Federation of Gynecology and Obstetrics Menstrual Disorders Working Group. PMID- 22065326 TI - Molecular and cellular causes of abnormal uterine bleeding of endometrial origin. AB - Women today may reasonably anticipate in the order of some 400 menstrual cycles over their reproductive lifespan. The endometrium is thus subject to repeat cycles of shedding and repair and notably healing of the endometrium post menses is "scarless". The local molecular and cellular mechanisms involved in post menstrual resolution of the inflammatory events associated with menstruation and endometrial repair remain to be fully determined. Menstrual complaints are common. It is highly likely that unrestrained local inflammatory events and/ or deficient repair processes within the endometrium contribute to the women's experience of heavy menstrual bleeding (HMB). The management of women with HMB may need to utilize therapeutic approaches that optimize endometrial repair processes, post menses. These approaches may be necessary in addition to current therapies that hitherto have focused on limiting the local inflammation associated with menstruation. Research endeavors thus need to focus upon the molecular and cellular causes of problematic uterine bleeding. Herein the events associated with pre-menstrual progesterone withdrawal, limitation of blood loss, the expression of vasoactive mediators and factors that may modulate vascular morphology are described. Such lines of enquiry and knowledge will be essential if novel targets for treatment of menstrual bleeding complaints, such as HMB, are to be identified. PMID- 22065327 TI - The need for investigations to elucidate causes and effects of abnormal uterine bleeding. AB - This article describes a modern perspective on the basic investigations for abnormal uterine bleeding (AUB) in low-resource settings compared with a much more detailed approach for high-resource settings, bearing in mind issues of effectiveness and cost effectiveness. AUB includes any one or more of several symptoms, and it should be evaluated for the characteristics of the woman's specific bleeding pattern, her "complaint" and the presence of other symptoms (especially pain), the impact on several aspects of body functioning and lifestyle, and the underlying cause(s), especially cancer. Ideally, the evaluation is comprehensive, considering each of the potential etiological domains defined by the International Federation of Gynecology and Obstetrics PALM COEIN system for the classification of causes. However, the detail of the questions and the extent of investigations will be significantly influenced by the technologies available and the time allotted for a consultation. In general, investigations should be performed only if they will make a material difference to the management approaches that can be offered. This should be an important consideration when a range of costly high-technology tests is accessible or when certain tests only have limited availability. PMID- 22065328 TI - The structured menstrual history: developing a tool to facilitate diagnosis and aid in symptom management. AB - Abnormal uterine bleeding (AUB) is a prevalent symptom that encompasses abnormalities in menstrual regularity, duration, frequency and/or volume, and it is encountered frequently by both primary care physicians and obstetrician gynecologists. Research on AUB has used numerous methods to measure bleeding and assess symptoms, but the lack of universally accepted outcome measures hinder the quality of research and the ability of clinical investigators to collaborate in multicenter trials. Similarly, clinical care for women reporting heavy, prolonged, or irregular menstrual bleeding is not optimized because standard ways of evaluating symptoms and change in symptoms over time do not exist. This article describes (1) the current methods of evaluating women with AUB, both in research and clinical care; and (2) offers suggestions for the development of a standardized structured menstrual history for use in both research and clinical care. PMID- 22065329 TI - An international response to questions about terminologies, investigation, and management of abnormal uterine bleeding: use of an electronic audience response system. AB - More than 600 registrants attended a two-hour interactive symposium on abnormal uterine bleeding (AUB) at the Federation of Gynecology and Obstetrics World Congress in Cape Town, October 2009. Nearly 250 of these participants answered multiple questions through an electronic audience responder system. The audience heard five structured presentations on clinically important and controversial aspects of AUB, including terminologies and definitions, classification of causes, mechanisms of AUB in the absence of structural lesions of the reproductive tract, the potential for a structured menstrual history, and management of heavy menstrual bleeding (HMB) in low-resource settings. Numerous demographic details were collected, and a total of 30 questions to the audience were interspersed through each of the presentations. The audience demonstrated great variation in the way the terms AUB, menorrhagia, and dysfunctional uterine bleeding (DUB) are used, and considerable majorities agreed that the terms menorrhagia and DUB should be abolished. AUB should be the overarching term to describe all symptomatic departures from normal menstruation or the menstrual cycle. HMB is a suitable replacement term for menorrhagia. DUB can be replaced by the three clinical entities comprising "nonstructural" causes of AUB. There was a high consistency across demographic subgroups in answers to most questions. Acute and chronic AUB were defined, and aspects of a classification system for causes of AUB and of a structured menstrual history were explored. Issues related to investigation and hormonal treatment of HMB in low-resource settings were explored by registrants from developing countries. PMID- 22065330 TI - Management of abnormal uterine bleeding in low- and high-resource settings: consideration of cultural issues. AB - In non industrialized countries the incidence of heavy menstrual bleeding (HMB) appears to be similar to that of industrialized countries, although data is scanty. In low-resource settings, women with abnormal uterine bleeding (AUB) often delay seeking medical care because of cultural beliefs that a heavy red menstrual bleed is healthy. Efforts to modify cultural issues are being considered. A detailed history and a meticulous examination are the important foundations of a definitive diagnosis and management in low-resource settings but are subject to time constraints and skill levels of the small numbers of health professionals. Women's subjective assessment of blood loss should be combined, if possible, with a colorimetric hemoglobin assessment, if full blood count is not possible. Outpatient endometrial sampling, transvaginal sonography, and hysteroscopy are available in some non industrialized countries but not in the lowest resource settings. After exclusion of serious underlying pathology, hematinics should be commenced and antifibrinolytic or nonsteroidal anti inflammatory drugs considered during menses to control the bleeding. Intrauterine or oral progestogens or the combined oral contraceptive are often the most cost effective long-term medical treatments. When medical treatment is inappropriate or has failed, the surgical options available most often are myomectomy or hysterectomy. Hysteroscopic endometrial resection or newer endometrial ablation procedures are available in some centers. If hysterectomy is indicated the vaginal route is the most appropriate in most low-resource settings. In low resource settings, lack of resources of all types can lead to empirical treatments or reliance on the unproven therapies of traditional healers. The shortage of human resources is often compounded by a limited availability of operative time. Governments and specialist medical organizations have rarely included attention to AUB and HMB in their health programs. Local guidelines and attention to training of doctors, midwives, and traditional health workers are critical for prevention and improvement in management of HMB and its consequences for iron deficiency anemia and postpartum hemorrhage, the major killer of young women in developing countries. PMID- 22065331 TI - 5-Meth-oxy-2-{[4-(morpholin-4-yl)phen-yl]imino-meth-yl}phenol. AB - In the title compound, C(18)H(20)N(2)O(3), the dihedral angle between the two aromatic rings is 33.66 (6) degrees . The morpholine ring adopts a chair conformation. The mol-ecular structure is stabilized by an intra-molecular O-H?N hydrogen bond. In the crystal, mol-ecules are linked via weak inter-molecular C H?O and C-H?pi inter-actions. PMID- 22065332 TI - Air embolism and blunt chest trauma. PMID- 22065333 TI - Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors. AB - BACKGROUND: Seizures after cardiac surgery are a serious complication. The antifibrinolytic agent tranexamic acid (TA), which has known proconvulsant properties, may be associated with postoperative seizures. We sought to determine the association between TA and other risk factors for seizures after cardiac surgery. METHODS AND RESULTS: We analyzed a database of consecutive cardiac surgery patients (April 2003 to December 2009) using multivariable logistic regression analysis to assess for seizure risk factors. Seizures occurred in 56 of 5,958 patients (0.94%). TA use was associated with an increased risk of seizures (odds ratio 7.4, 95% confidence interval 2.8-19.3; P < 0.001). Multivariable logistic regression analysis revealed that the following factors were significantly associated with seizures: TA exposure; Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score > 20; preoperative cardiac arrest; preoperative neurological disease; open chamber surgery; cardiopulmonary bypass time > 150 min; and previous cardiac surgery. Seizures occurred at a median of 5.3 hr (interquartile range 2.4-15.1 hr) after the end of surgery. In all, 58.1% were grand mal, 14.5% were associated with a stroke, and 58.1% recurred in hospital. Altogether, 48.3% of the patients were able to discontinue anticonvulsant medications prior to discharge. Compared to the non-seizure group, seizure patients had an increased rate of postoperative neurological complications, defined as delirium and/or stroke (3.2% vs 19.6%, P < 0.001), increased intensive care unit (ICU) length of stay (1.0 vs 4.7 days, P < 0.001), and increased ICU mortality (1.4 % vs 9.7 %, P = 0.001). CONCLUSIONS: Our data suggest that multiple risk factors, including TA, are associated with seizures after cardiac surgery. Thus, the TA dose may be a readily modifiable risk factor for postoperative seizures. PMID- 22065334 TI - 'The body gets used to them': patients' interpretations of antibiotic resistance and the implications for containment strategies. AB - BACKGROUND: Interventions promoting evidence based antibiotic prescribing and use frequently build on the concept of antibiotic resistance but patients and clinicians may not share the same assumptions about its meaning. OBJECTIVE: To explore patients' interpretations of 'antibiotic resistance' and to consider the implications for strategies to contain antibiotic resistance. DESIGN: Multi country qualitative interview study. PARTICIPANTS: One hundred and twenty-one adult patients from primary care research networks based in nine European countries who had recently consulted a primary care clinician with symptoms of Lower Respiratory Tract Infection (LRTI). APPROACH: Semi-structured interviews with patients following their consultation and subjected to a five-stage analytic framework approach (familiarization, developing a thematic framework from the interview questions and the themes emerging from the data, indexing, charting, and mapping to search for interpretations in the data), with local network facilitators commenting on preliminary reports. RESULTS: The dominant theme was antibiotic resistance as a property of a 'resistant human body', where the barrier to antibiotic effectiveness was individual loss of responsiveness. Less commonly, patients correctly conceptualized antibiotic resistance as a property of bacteria. Nevertheless, the over-use of antibiotics was a strong central concept in almost all patients' explanations, whether they viewed resistance as located in either the body or in bacteria. CONCLUSIONS: Most patients were aware of the link between antibiotic use and antibiotic resistance. The identification of the misinterpretation of antibiotic resistance as a property of the human body rather than bacterial cells could inform clearer clinician-patient discussions and public health interventions through emphasising the transferability of resistance, and the societal contribution individuals can make through more appropriate antibiotic prescribing and use. PMID- 22065335 TI - The relationship between distal and proximal colonic neoplasia: a meta-analysis. AB - OBJECTIVES: To investigate the association between proximal colonic neoplasia and distal lesions as a function of the lesion type. The extent to which health, demographic, and study characteristics moderate this association was also examined. DATA SOURCES: Google Scholar, Web of Science, Scopus, and PubMed. STUDY ELIGIBILITY CRITERIA: Studies allowing the calculation of OR of proximal neoplasia (PN) and proximal advanced neoplasia (PAN) for distal hyperplastic polyps (HP), nonadvanced adenomas (NAA), adenomas (AD), and advanced neoplasia (AN); also, studies for which the proportions of subjects with isolated (i.e., not accompanied by distal lesions) PN (IPN) and PAN (IPAN) over the total number of subjects with PN or PAN could be calculated. STUDY APPRAISAL AND SYNTHESIS METHODS: Thirty-two studies were included for calculating OR between proximal neoplasia and distal lesions and 40 studies for proportions of IPN and IPAN. Subgroup analyses were conducted for presence of symptoms, prevalence of PN and PAN, age, proportion of males, geographic region, study design, and demarcation point. RESULTS: The association between distal lesions and proximal neoplasia increased with the severity of the distal lesions. Odds of PN were higher in subjects with HP compared to subjects with a normal distal colon. Odds of PN and PAN were higher in subjects with NAA, AD, and AN than in subjects with a normal distal colon. PAN were more strongly associated with distal lesions in asymptomatic populations, in young populations, and in populations with a low prevalence of PAN. In approximately 60% of the subjects with PN and PAN, these neoplasia were isolated. LIMITATIONS: The present results may be affected by publication bias and dichotomization in the subgroup analyses. Limitations related to the individual studies include self-selection, lesion misclassification and misses, and technological advances leading to changes in the detection of lesions during the time span of the included studies. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: All types of distal lesions are predictive of PN. All types of distal neoplasia are predictive of PAN. The association between distal lesions and proximal neoplasia increases with the severity of the distal lesion. The association between distal lesions and proximal advanced neoplasia is stronger in low-risk groups as compared to high risk groups. PMID- 22065336 TI - Triptolide attenuate the oxidative stress induced by LPS/D-GalN in mice. AB - Triptolide, a diterpene triepoxide, is one of the major components of most functional extracts of Tripterygium wilfordii Hook f, which is known to have various biological effects, including immunosuppressive, anti-inflammatory and anti-tumor functions. We studied the inhibitory effect of triptolide on endotoxemia (ETM)-induced oxidative stress, which was induced in C57BL/6 mice by lipopolysaccharide (LPS) and D-galactosamine (D-GalN). Pretreatment with triptolide decreased the reactive oxygen species (ROS) levels, mortality rate and liver injury after LPS/D-GalN injection. We utilized comprehensive proteomics to identify alterations in liver protein expression during pretreatment with triptolide or N-acetylcysteine (NAC) after LPS/D-GalN injection, 44 proteins were found to be related to oxidative stress, mitochondria, metabolism and signal transduction, and 23 proteins of them seemed to be significantly up- or down regulated. Furthermore, both triptolide and NAC inhibited activation of c-jun NH2 terminal kinases (JNK) and mitogen-activated protein kinase p38 (p38), phosphorylation of inhibitor of nuclear factor-kappa B (IkappaB) and activation of nuclear factor-kappaB (NF-kappaB). These results demonstrated that triptolide inhibited the activation of JNK and p38 by decreasing ROS levels, which in turn inhibited the hepatic injury. In addition, we set and validated the phosphorylation model of extracellular signal-regulated kinase (ERK) and proposed that triptolide probably induced ERK phosphorylation through inhibiting its dephosphorylation rates. These results showed that triptolide can effectively reduce the oxidative stress and partially rescue the damage in the liver induced by LPS/D-GalN. PMID- 22065337 TI - [Comments on the article "Motivation of female surgeons - pleasure or burden" by C. Stroh (Zentralbl Chir 2010; 135: 447-450)]. PMID- 22065338 TI - [Reno-pulmo-aortal fibromuscular dysplasia causing angiorrhexis and mimicking pheochromocytoma / paraganglioma - case report]. PMID- 22065339 TI - [Therapy of paediatric pancreatic trauma]. AB - BACKGROUND: The goal of this clinical study is to evaluate diagnostics and therapeutical strategies for paediatric pancreatic trauma. It is assumed that conservative treatment is at least as good as operative treatment. PATIENTS / MATERIAL AND METHODS: In a retrospective study 36 children with pancreatic trauma treated between the years 1987 and 2010 in the paediatric surgery department of the University Medical Centre Mannheim were included. Injury grades, diagnostics and treatment were evaluated. RESULTS: In a collective of 36 patients with an average age of seven years the following injuries were found: 26 grade 1, three grade 2, five grade 3 and two grade 4 injuries. Eight patients presented with polytrauma, 20 showed additional injuries. Initial levels of amylase and lipase and screening ultrasound were not always sensitive. 18 patients received conservative treatment. The remaining 18 were operated: either exploratory laparotomy and drainage or pancreas reconstruction with inner stenting or distal pancreatic resection were performed. Pancreatic pseudocysts were drained by transgastric stenting. CONCLUSION: 20 years ago blunt pancreatic trauma was usually treated operatively. Today grade 1 and grade 2 injuries should be treated conservatively. Higher graded pancreatic ductal injuries can be managed operatively with ductal stenting and organ conservation. Pancreatic resections are not always necessary. Endoscopic transgastric drainage of persisting pancreatic pseudocysts is also successful in children. PMID- 22065340 TI - [Diverticulosis as a risk factor for foreign body-associated bowel perforation]. PMID- 22065341 TI - Functional importance of laparoscopic sleeve gastrectomy for the lower esophageal sphincter in patients with morbid obesity. AB - BACKGROUND: Obesity is characterized by excess body fat measured in body mass index (BMI), which is the weight in kilograms (kg) divided by the height in square meters [m(2)]. In the Northern Hemisphere, the prevalence of overweight has increased by up to 34%. This situation is associated with high incidence of comorbidities such as gastroesophageal reflux disease. Bariatric surgery is the only effective treatment for severe obesity, resulting in amelioration of obesity comorbidities. Data on LES competence following sleeve gastrectomy (SG), one of the several bariatric procedures, are conflicting. METHODS: In a prospective study, we enrolled 37 patients and divided them into two subgroups in order to evaluate lower esophageal sphincter pressure (LESP) and esophageal motility before and after laparoscopic sleeve gastrectomy (LSG) by means of stationary esophageal manometry. A study collective also underwent a gastroscopy. Participants (20) were healthy controls who volunteered. RESULTS: Preoperative median BMI in group I (control) differed statistically significantly (p < 0.0001) as compared to groups II and III (22 vs. 50.5 or 47.5 kg/m2, respectively). After LSG, the BMI of groups II and III decreased to 39.5 and 45 kg/m2, respectively. Postoperatively, LESP increased significantly, namely, from preoperative 8.4 to 21.2 mmHg in group II and from 11 to 24 mmHg (p < 0.0001) in group III. Tubular esophageal motility profits from LSG. As expected, the gastroscopy findings ranged from cardiac insufficiency, esophagitis and hiatal hernia to gastric ulcer. CONCLUSION: LSG significantly increased lower esophageal pressure independent of weight loss after LSG and may protect obese patients from gastroesophageal reflux. PMID- 22065342 TI - Lean and fat mass loss in obese patients before and after Roux-en-Y gastric bypass: a new application for ultrasound technique. AB - OBJECTIVE: This study aims to evaluate the thickness of the femoral quadriceps and biceps brachii and brachialis muscles bilaterally and the adjacent subcutaneous fat in patients undergoing gastric bypass Roux-en-Y before and after surgery, using ultrasound as the diagnostic method of choice. METHODS: We studied 12 patients undergoing this surgical method preoperatively and during the first, third, and sixth postoperative months. During these periods, patients were evaluated by ultrasound to determine the thickness of subcutaneous adipose tissue and muscle of the upper and lower limbs. RESULTS: Postoperatively, these patients showed a reduction in the thickness of the upper and lower extremities muscle and adipose tissue as compared to their preoperative values. There was a significant difference in the loss of muscle thickness in all postoperative months and in the thickness of fatty tissue in the sixth month after surgery, compared to the preoperative muscle and fatty tissue thickness. CONCLUSIONS: Ultrasound can be considered as the diagnostic method of choice when assessment of the fat and lean body mass is required in morbidly obese patients before and after bariatric surgery. PMID- 22065343 TI - Organophosphate and phthalate esters in standard reference material 2585 organic contaminants in house dust. AB - The levels of 22 phthalate diesters (phthalates) and organophosphate triesters (organophosphates) have been investigated in standard reference material 2585 (SRM 2585) "organic contaminants in house dust." Ultrasonic-assisted solvent extraction and solid-phase extraction on a Florisil adsorbent were used as the extraction and cleanup steps combined with analysis using gas chromatography tandem mass spectrometry in positive ion chemical ionization mode. Seven phthalates were detected in the concentration range 1-570 MUg/g. Di(2-ethylhexyl) phthalate was the major phthalate present at 570 MUg/g. Ten organophosphates were detected in SRM 2585. Tris(2-butoxyethyl) phosphate was the predominant organophosphate at 82 MUg/g, and nine organophosphates were determined at concentrations ranging from 0.19 to 2.3 MUg/g. Five organophosphates were below the method detection limit, of which two were in level with the procedural blank. The applied extraction and cleanup method was evaluated for the analysis of SRM 2585. The extraction yield was >=99%, except for tris(2-chloroethyl) phosphate (97%) and diethyl phthalate (98.5%). The problem of calibration curvature is addressed, and it is shown that the use of deuterated standards improves the analysis. The concentrations of ten organophosphate esters were determined in SRM 2585, and seven of these were compared with existing data. To our knowledge, this is the first report of the levels of the seven phthalates esters in SRM 2585 "organic contaminants in house dust." PMID- 22065344 TI - Analysis of the bioactivity of magnetically immunoisolated peroxisomes. AB - Peroxisomes produce reactive oxygen species which may participate in biotransformations of innate biomolecules and xenobiotics. Isolating functional peroxisomes with low levels of contaminants would be a useful tool to investigate biotransformations occurring in these organelles that are usually confounded with biotransformations occurring in other co-isolated organelles. Here, we immunoisolate peroxisomes and demonstrate that the impurity level after isolation is low and that peroxisomes retain their biological activity. In this method, an antibody targeting a 70-kDa peroxisomal membrane protein was immobilized to silanized magnetic iron oxide beads (1-4 MUm in diameter) coated with Protein A. Peroxisomes from L6 rat myoblast homogenates were magnetically captured, washed, and then analyzed for subcellular composition using enzymatic assays. Based on the ratio of peroxisomal to lysosomal activity, the retained fraction is 70-fold enriched relative to the unretained fraction. Similarly, the ratio of peroxisomal activity to mitochondrial content suggests that the retained fraction is >30-fold enriched relative to the unretained fraction. H(2)O(2) production from the beta oxidation of palmitoyl-CoA demonstrated that the isolated peroxisomal fraction was biologically active. Capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) analysis confirmed that the immunopurified fractions were capable of transforming the anticancer drug doxorubicin and the fatty acid analog, BODIPY 500/510 C1C12. Besides its use to investigate peroxisome biotransformations in health and disease, the combination of magnetic immunoisolation with CE-LIF could be widely applicable to investigate subcellular specific biotransformations of xenobiotics occurring at immunoisolated subcellular compartments. PMID- 22065345 TI - Electrochemical uranyl biosensor with DNA oligonucleotides as receptor layer. AB - The feasibility of using gold electrodes modified with short-chain ssDNA oligonucleotides for determination of uranyl cation is examined. Interaction between UO(2)(2+) and proposed recognition layer was studied by means of voltammetric and quartz crystal microbalance measurements. It was postulated that ssDNA recognition layer functions via strong binding of UO(2)(2+) to phosphate DNA backbone. The methylene blue was used as a redox marker for analytical signal generation. Biosensor response was based on the difference in electrochemical signal before and after subjecting it to sample containing uranyl ion. The lower detection limit of 30 nmol L(-1) for UO(2)(2+) was observed for a sample incubation time of 60 min. Proposed ssDNA-modified electrodes demonstrated good selectivity towards UO(2)(2+) against common metal cations, with only Pb(2+) and Ca(2+) showing considerable interfering effect. PMID- 22065346 TI - Headspace gas chromatography-mass spectrometry for rapid determination of halonitromethanes in tap and swimming pool water. AB - Halonitromethanes (HNMs) are one of the most cytotoxic and genotoxic classes found among the unregulated disinfection by-products formed by the reaction of chemical disinfectants with natural organic matter in water. Typical methods used to determine these compounds in water (mainly trichloronitromethane) are based on the Environmental Protection Agency (EPA) method 551.1 using liquid-liquid extraction. A fast and straightforward method for the determination of the nine HNMs in water has been developed using a static headspace (HS) coupled with gas chromatography-mass spectrometry (GC-MS). Important parameters controlling headspace extraction were optimised to obtain the highest sensitivity: 250 MUL of methyl tert-butyl ether (as a chemical modifier) and 6 g of anhydrous sodium sulphate were added to the water sample; an oven temperature of 80 degrees C and an equilibration time of 20 min were also selected. The addition of a chemical modifier favoured the volatilisation of all HNMs, increasing their signals up to approximately four times. Under optimum conditions, the method developed provides limits of detection between 0.03 and 0.60 MUg/L and a relative standard deviation of ~6.0%. The developed method was validated and then compared with the reference method EPA 551.1 for the analysis of tap and swimming pool water. A good agreement in the results was observed, which corroborated the good performance of the proposed HS-GC-MS method. PMID- 22065347 TI - Identification of phospholipid species affected by miltefosine action in Leishmania donovani cultures using LC-ELSD, LC-ESI/MS, and multivariate data analysis. AB - Leishmaniasis is a widespread parasitic disease principally treated by intravenous drugs. Hexadecylphosphocholine (miltefosine) has recently proved its efficacy by oral route. Although its mechanism of action has been investigated, and principally relies on perturbations of the metabolism of lipids and especially phospholipids, further studies need to be conducted to detect precisely which metabolic pathways are impacted. For this purpose, the present work proposes a complete lipidomic study focused on membrane phospholipids of clones of Leishmania donovani non-treated (NT), treated (T) and resistant (R) to miltefosine. Firstly, a separation of phospholipids in normal phase high performance liquid chromatography (NP-HPLC) was coupled to a mass spectrometer (MS) equipped with an electrospray (ESI) ion source, and response was compared to evaporative light scattering detection (ELSD). Secondly, a quantification of phospholipid classes was performed using NP-HPLC/ESI/MS on NT, T and R clones of L. donovani. Thirdly, full-scan acquisitions of analyzed samples were compared using orthogonal signal correction-partial least square-discriminant analysis (OSC-PLS-DA) to highlight phospholipid molecular species of interest between the three types of clones. Structural determination of the most relevant species has finally been performed using tandem mass spectrometry. A first hypothesis on the effect of miltefosine on lipid metabolic pathways is then proposed. PMID- 22065348 TI - Fragmentation methods on the balance: unambiguous top-down mass spectrometric characterization of oxaliplatin-ubiquitin binding sites. AB - The interaction between oxaliplatin and the model protein ubiquitin (Ub) was investigated in a top-down approach by means of high-resolution electrospray ionization mass spectrometry (ESI-MS) using diverse tandem mass spectrometric (MS/MS) techniques, including collision-induced dissociation (CID), higher-energy C-trap dissociation (HCD), and electron transfer dissociation (ETD). To the best of our knowledge, this is the first time that metallodrug-protein adducts were analyzed for the metal-binding site by ETD-MS/MS, which outperformed both CID and HCD in terms of number of identified metallated peptide fragments in the mass spectra and the localization of the binding sites. Only ETD allowed the simultaneous and exact determination of Met1 and His68 residues as binding partners for oxaliplatin. CID-MS/MS experiments were carried out on orbitrap and ion cyclotron resonance (ICR)-FT mass spectrometers and both instruments yielded similar results with respect to number of metallated fragments and the localization of the binding sites. A comparison of the protein secondary structure with the intensities of peptide fragments generated by collisional activation of the [Ub+Pt-(chxn)] adduct [chxn = (1R,2R)-cyclohexanediamine] revealed a correlation with cleavages in solution phase random coil areas, indicating that the N-terminal beta-hairpin and alpha-helix structures are retained in the gas phase. PMID- 22065349 TI - Qualitative studies on the metabolism and the toxicological detection of the fentanyl-derived designer drugs 3-methylfentanyl and isofentanyl in rats using liquid chromatography-linear ion trap-mass spectrometry (LC-MS(n)). AB - The opioid 3-methylfentanyl, a designer drug of the fentanyl type, was scheduled by the Controlled Substance Act due to its high potency and abuse potential. To overcome this regulation, isofentanyl, another designer fentanyl, was synthesized in a clandestine laboratory and seized by the German police. The aims of the presented study were to identify the phase I and phase II metabolites of 3 methylfentanyl and isofentanyl in rat urine, to identify the cytochrome P450 (CYP) isoenzymes involved in their initial metabolic steps, and, finally, to test their detectability in urine. Using liquid chromatography (LC)-linear ion trap mass spectrometry (MS(n)), nine phase I and five phase II metabolites of 3 methylfentanyl and 11 phase I and four phase II metabolites of isofentanyl could be identified. The following metabolic steps could be postulated for both drugs: N-dealkylation followed by hydroxylation of the alkyl and aryl moiety, hydroxylation of the propanamide side chain followed by oxidation to the corresponding carboxylic acid, and, finally, hydroxylation of the benzyl moiety followed by methylation. In addition, N-oxidation of isofentanyl could also be observed. All hydroxy metabolites were partly excreted as glucuronides. Using recombinant human isoenzymes, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 were found to be involved in the initial metabolic steps. Our LC-MS(n) screening approach allowed the detection of 0.01 mg/L of 3-methylfentanyl and isofentanyl in spiked urine. However, in urine of rats after the administration of suspected recreational doses, the parent drugs could not be detected, but their common nor metabolite, which should therefore be the target for urine screening. PMID- 22065350 TI - Double-stranded Let-7 mimics, potential candidates for cancer gene therapy. AB - MicroRNAs (miRNAs), a class of small, single-stranded endogenous RNAs, act as post-transcriptional regulators of gene expression. The ability of one single miRNA regulating multiple functionally related mRNAs makes it a new potential candidate for cancer gene therapy. Let-7s miRNAs have been demonstrated as tumor suppressor genes in various types of cancers, providing one choice of gene therapy by replenishing this miRNA. In the present studies, we demonstrate that the chemically synthesized, double-stranded Let-7 mimics can inhibit the growth and migration and induce the cell cycle arrest of lung cancer cell lines in vitro. Let-7 mimics silence gene expression by binding to the 3' UTR of targeting mRNAs. Mutation of seed sequence significantly depresses the gene silencing activity of Let-7 mimics. Our results also demonstrate that it is possible to increase the activity of Let-7s through mutating the sequence within the 3'end of the antisense strand. Directly, co-transfection Let-7 mimics with active siRNAs impairs the anti-cancer activities of Let-7 mimics. However, a 3-h interval between the introduction of Let-7 mimics and a kind of siRNA avoids the competition and enhances the anti-cancer activities of Let-7 mimics. Taken together, these results have revealed that Let-7s mimics are potential candidates for cancer gene therapy. PMID- 22065351 TI - The changing face of family medicine. PMID- 22065353 TI - Black hairy tongue in an infant. PMID- 22065352 TI - Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study. AB - BACKGROUND: Combined oral contraceptives are a common method of contraception, but they carry a risk of venous and arterial thrombosis. We assessed whether use of drospirenone was associated with an increase in thrombotic risk relative to third-generation combined oral contraceptives. METHODS: Using computerized records of the largest health care provider in Israel, we identified all women aged 12 to 50 years for whom combined oral contraceptives had been dispensed between Jan. 1, 2002, and Dec. 31, 2008. We followed the cohort until 2009. We used Poisson regression models to estimate the crude and adjusted rate ratios for risk factors for venous thrombotic events (specifically deep vein thrombosis and pulmonary embolism) and arterial thromboic events (specifically transient ischemic attack and cerebrovascular accident). We performed multivariable analyses to compare types of contraceptives, with adjustment for the various risk factors. RESULTS: We identified a total of 1017 (0.24%) venous and arterial thrombotic events among 431,223 use episodes during 819 749 woman-years of follow up (6.33 venous events and 6.10 arterial events per 10,000 woman-years). In a multivariable model, use of drospirenone carried an increased risk of venous thrombotic events, relative to both third-generation combined oral contraceptives (rate ratio [RR] 1.43, 95% confidence interval [CI] 1.15-1.78) and second generation combined oral contraceptives (RR 1.65, 95% CI 1.02-2.65). There was no increase in the risk of arterial thrombosis with drospirenone. INTERPRETATION: Use of drospirenone-containing oral contraceptives was associated with an increased risk of deep vein thrombosis and pulmonary embolism, but not transient ischemic attack or cerebrovascular attack, relative to second- and third generation combined oral contraceptives. PMID- 22065354 TI - Potential pitfalls of "specialized" primary care. PMID- 22065355 TI - The practicality of practice guidelines. PMID- 22065357 TI - New network created to assess drug safety. PMID- 22065358 TI - Risk of venous thromboembolism with oral contraceptives. PMID- 22065360 TI - A comprehensive view of focused practices. PMID- 22065359 TI - Breast reconstruction after mastectomy for breast cancer. PMID- 22065361 TI - Addressing the social causes of poor health is integral to practising good medicine. PMID- 22065362 TI - Canada's laws on pharmaceutical intellectual property: the case for fundamental reform. PMID- 22065363 TI - Improving primary health care delivery: still waiting for the magic bullet. PMID- 22065365 TI - Learning to retire gracefully. PMID- 22065366 TI - Chloridodiphen-yl{[1-(1,3-thia-zol-2-yl-kappaN)ethyl-idene]-4-phenyl-thio semicarbazidato-kappaN,S}tin(IV) methanol monosolvate. AB - The title compound, [Sn(C(6)H(5))(2)(C(12)H(11)N(4)S(2))Cl].CH(4)O, is formed during the reaction between 2-acetyl-thia-zole 4-phenyl-thio-semicarbazone (Hacthptsc) and diphenyl-tin(IV) dichloride in methanol. In the crystal structure, the Sn atom exhibits an octa-hedral geometry with the [N(2)S] anionic tridentate thio-semicarbazone ligand having chloride trans to the central N and the two phenyl groups trans to each other. The Sn-Cl distance is 2.5929 (6), Sn-S is 2.4896 (6) and Sn-N to the central N is 2.3220 (16) A. The MeOH mol-ecules link the Sn complexes into one-dimensional chains via N-H?O and O-H?Cl hydrogen bonds. PMID- 22065367 TI - Increased expression of the histamine H4 receptor subtype in hypertrophic differentiation of chondrogenic ATDC5 cells. AB - Histamine has been regarded as an inflammatory mediator of arthritic disorders. We have previously reported that the expression of histamine H(4) receptor (H(4)R) mRNA in synovial tissues was significantly higher in patients with osteoarthritis (OA) compared to those with rheumatoid arthritis. Chondrocyte hypertrophy and endochondral ossification are essential processes in pathologic disorders such as osteophyte formation during OA progression. In the present study, we examined the expression of H(4) R during differentiation into hypertrophic chondrocytes in the ATDC5 cells, a widely used in vitro model of chondrogenic differentiation. Quantitative reverse transcription polymerase chain reaction showed that the levels of histidine decarboxylase and H(4)R mRNA on ATDC5 cells were increased in a time-dependent manner during the culture period. By contrast, the expressions of H(1)R and H(2)R were not increased from day 7 onwards. The mRNA expression of the hypertrophic chondrocyte marker type X collagen (COL X) was increased markedly from 14 to 21. Immunocytochemical analysis indicated that H(4)R staining was strongly immunoreactive on the plasma membrane of ATDC5 cells. Flow cytometry showed increased expression of H(4)R and COL X protein in ATDC5 chondrocytes. Furthermore, the majority of the COL X positive cells expressed H(4) R throughout the culture period. In summary, we showed for the first time that H(4)R is expressed in ATDC5 chondrocytes. Moreover, we found that most hypertrophic chondrocytes express H(4)R, suggesting that this receptor might be associated with the differentiation of chondrocytes into hypertrophic cells, which are abnormally observed in joint lesions in OA. PMID- 22065368 TI - The repair of the Achilles tendon rupture: comparison of two percutaneous techniques. AB - This study proposes a comparison between two percutaneous techniques of subcutaneous Achilles tendon rupture by evaluating the risk of lesion developing, the morbidity of the surgical technique adopted and the effectiveness of each technique. Sixty patients were operated at Padua Orthopaedic Clinic by using the two different procedures: (1) Ma and Griffith in 30 cases and (2) Tenolig in 30 cases. Risk of rupture developing has been evaluated in relation to sex, age, side, kind of trauma, work and presence of preoperative risk factors. The Morbidity of surgical technique has been evaluated in with respect to surgical time, hospital permanence, immobilization, active nonweight-bearing mobilization, assisted weight bearing until the full one, number of early and late complications before and after hospital discharge. Effectiveness has been evaluated in relation to return time to common life, work and sport; anatomical and functional features have been evaluated using McComis score, rating results as: very good (from 80 to 70), good (from 69 to 60), fair (from 59 to 50) and poor (<50). Tenolig group shows shorter average time from hospital admission and operation, hospital permanence and immobilization (P < 0.05), and it results in an easier and quicker execution and functionally stimulates the tendon healing in a short time. Effectiveness was the same for both techniques because average McComis score was good (P = 0.35), and there was no significant differences in common life returning time (P = 0.12). Tenolig technique seems to be preferable to Ma and Griffith. PMID- 22065369 TI - Effects of atopic dermatitis on the morphology and water content of scalp hair. AB - The effects of atopic dermatitis (AD) on scalp hair properties, such as morphology and water content, were investigated using atomic force microscopy (AFM) and thermogravimetric analyzer. Hairs from lesional and nonlesional scalp regions of eight patients with AD were investigated. The severity of the disease, which was evaluated using the SCORing Atopic Dermatitis index, was 48.75 (range, 40-80). Hairs from 15 normal adults were also examined as controls. The surface images were taken in an area of 20 * 20 MUm(2) with 512 * 512 pixels and a scan speed of 0.8 line/s. AD affected the cuticle structures and scales of scalp hair. The edges of cuticles were torn and collapsed, and the scales were very thick. The water contents of both types of AD hair were less than the control: 12% +/- 0.7%, 11.7% +/- 0.4%, and 13% +/- 0.8% for lesional AD hair, nonlesional AD hair, and control hair, respectively. The scalp hair of patients with AD can be characterized by thick and globular scale patterns. The hair of patients with AD has less water content than normal hair showing a good agreement with the property of skin having AD. PMID- 22065370 TI - Pressure immobilization after North American Crotalinae snake envenomation. PMID- 22065371 TI - Commentary: pressure bandaging for North American snake bite? No! AB - This issue of The Journal of Medical Toxicology includes a position statement regarding the use of pressure immobilization for the pre-hospital treatment of North American Crotalinae envenomation. This commentary discusses the background behind the creation of the position statement and explores the issues involved in applying science to real-world public health recommendations and practice. PMID- 22065372 TI - [Deep infection after treatment of proximal femur fractures--results and assessment of life quality]. AB - BACKGROUND: Proximal femur fractures are the second most prevalent fractures in patients older than 65 years. Despite large improvements in implant design and surgical technique, complications in fracture healing are very common. Deep infection after osteosynthetic treatment is considered to be one of the major complications with a high rate of mortality. Little is known about the adequate treatment and results in patients with infection of proximal femur fractures. The aim of this study was to evaluate the different treatment options for eradication of infection as well as to analyse the clinical outcome and quality of life. PATIENTS AND METHODS: 40 patients treated for infected proximal femur fractures between 2001 and 2010 were retrospectively analysed. Quality of life was assessed in 21 patients after an average of 40 months using the WOMAC and the SF-12 score. RESULTS: Surgical treatment included complete removal of infected implants and radical debridement. In 20 patients resection arthroplasty had to be performed. Ten patients were treated with a modular prosthesis, 4 patients were treated with a proximal femur replacement. Due to severe infection and risk-increasing comorbidities, resection arthroplasty had to be performed in the remaining 12 patients. Re-osteosynthesis could be performed in 13 patients. Average time of treatment was 67 days. At the time of follow-up the rate of mortality proved to be 15%. The rate of reinfection was 14.6%. At the time of follow-up infection was still prevalent in 2 patients. Dislocation after the hip prosthesis occurred in 3 of 14 patients. Of the 13 patients who received re-osteosynthesis one patient suffered a reinfection. Delayed fracture healing was treated with spongiosa grafts in 2 cases. 33% of the patients with resection arthroplasty died during follow-up. Statistical analysis showed better results in WOMAC and SF-12 scores in patients with hip prosthesis. Patients with re-osteosynthesis showed a larger variation in results. CONCLUSION: Deep infection after osteosynthetic treatment of proximal femur fractures is a severe complication. Radical surgical treatment and adequate local and systemic antibiotic application can help clear an infection. Quality of life is significantly reduced. Treatment should therefore be adapted to the individual patient's condition. PMID- 22065373 TI - [Clostridium difficile-associated infections in a septic ward of a level 1 trauma centre: an analysis of 159 patients]. AB - BACKGROUND: Clostridium difficile-associated infections are severe nosocomial infections. In recent studies, dramatic increases of CD-associated infections for the U.S.A. and Germany have been described, which leads to additional risk for patients and higher costs. Despite several studies, there is no study available which analyses the incidence of CD-associated infections on a septic ward at a level 1 trauma centre. Therefore, this study was performed to analyse the incidence and risk factors of developing a CD-associated infection in septic trauma patients. MATERIAL AND METHODS: All patients treated between January 2002 and December 2009 at the septic ward of a level 1 trauma centre, who developed a CD-associated diarrhoea or pseudomembranous colitis, were included in this retrospective study. Information about age, sex, admission diagnosis, indication for antibiotic therapy, length of antibiotic therapy, number of administered antibiotics, length of hospital stay, type of treatment of the CD-associated infection as well as the mortality rate was gleaned from the patients' medical records. Furthermore, the relation of developing a CD-associated infection was determined for the following factors: (i) age > 65 years versus < 65 years; (ii) male versus female; (iii) single versus multiple antibiotic therapy; (iv) cephalosporins versus remaining antibiotic groups. RESULTS: Between January 2002 and December 2009 6378 patients with surgical infection were treated at our level 1 trauma centre, whereas a total of 159 patients (2.5%) developed during the hospital stay a Clostridium difficile-associated diarrhoea. The incidence of CD associated infection increased dramatically in 2009 and was more than quadrupled compared with 2002 or 2003. Patients over 65 years of age developed more frequently a CD-associated infection compared to patients less than 65 years of age (OR 1.96, 95% CI 1.4 to 2.7). There was no difference between males and females as well as between multiple antibiotic therapy and single antibiotic therapy (OR 0.96, 95% CI 0.7 to 1.3). Cephalosporins were the most often administered antibiotics with a median value of 45.9% followed by gyrase inhibitors with a median value of 17.2%. However, there were no differences between antibiotic groups (OR 1.11; 95% CI 0,87-1,5). CONCLUSIONS: In conclusion, CD-associated infections are frequent nascent infections on a septic ward at a level 1 trauma centre. This could result in a therapeutic dilemma in the future, especially in septic surgery, where antibiotic therapy is an essential component of the therapy. Thus, further prospective clinical and experimental studies are essential. PMID- 22065374 TI - [Comparative study on the strength of different mechanisms of operation of multidirectionally angle-stable distal radius plates]. AB - INTRODUCTION: Polyaxial angle-stable plating is thought to be particularly beneficial in the management of complex intra-articular fractures of the distal radius. The present study was performed to investigate the strength of polyaxial locking interfaces of distal radius plates. MATERIAL AND METHODS: We tested the polyaxial interfaces of 3 different distal radius plates (2.4 mm Variable Angle LCP Two-Column Volar Distal Radius Plate, Synthes, Palmar Classic, Konigsee Implantate and VariAx Plate Stryker). The strength of 0 degrees and 10 degrees screw locking angle was obtained during static loading. RESULTS: The strength of Palmar Classic with a 0 degrees locking angle is significantly the best of all tested systems. With a 10 degrees locking angle there is no significant difference between Palmar Classic, Two column Plate and VariAx Plate. CONCLUSION: The strength of polyaxial interfaces differs between the tested systems. A reduction of ultimate strength is due to increases of screw locking angle. The design of polyaxial locking interfaces should be investigated in human bone models. PMID- 22065375 TI - [Training adaptation of the Achilles tendon in competitive athletes--sonographic standard values for the Achilles tendon]. AB - BACKGROUND: Current theories and empirical results regarding the sonographic dimensions of the Achilles tendon as well as an alleged training adaptation of the tendon in competitive athletes are tested for the first time in a large in vivo sample. The pathological validity of a thickened tendon in competitive athletes is under scrutiny. MATERIAL AND METHOD: In addition to 202 national squad athletes from the German track and field federation, 199 age-matched normal individuals were examined sonographically. The portable ultrasound scanner Just Vision was used to compare 404 Achilles tendons of athletes with 398 Achilles tendons of normal individuals as to tendon diameter. Furthermore, pathologies were assessed. RESULTS: Achilles tendon diameter at the calcanear insertion was 4.2 +/- 0.72 mm on average. Athletes' tendons were thicker than normal tendons (p < 0.001) - athletes, however, also reported more clinical symptoms (p < 0.001). In athletes, increasing diameters were associated with more clinical problems as opposed to normal individuals. At the tendon waist, diameters above 6.0 mm were very likely to go along with pathologies. CONCLUSIONS: For the first time, valid data of Achilles tendon diameters in competitive athletes and normal individuals have been presented. The emerging pattern of results clearly contradicts the notion of a physiological training adaptation of the Achilles tendon. PMID- 22065376 TI - [Quality of documentation and care for victims of violence for the example of a trauma surgery emergency department in a major city]. AB - BACKGROUND: People who have become victims of violence have manifold problems. Besides medical diagnostics and therapy, it is necessary to recognise the situation in which these patients have become such victims, to document the consequences of this violence for use in court and to offer further assistance. Victims of violence often contact primarily a trauma ambulance. The optimisation of the medical treatment of the victims is a relevant traumatological topic, which so far has received only very scant attention. Therefore the aim of this study was to evaluate the necessity for an interdisciplinary combination of treatments for the targeted treatment of these victims. MATERIAL AND METHODS: Using a standardised data card a retrospective data analysis of all out-patients and all in-patients of a trauma centre with regard to the existence of a violent context was carried out for the year 2004. All such cases were included and the data were evaluated descriptively according to age, gender, information about the act of violence, consequences thereof, type and scope of the diagnostic findings, as well as inducements for further measures. In this context we differentiated between "domestic violence" and "public violence". RESULTS: The data of 7132 patients were evaluated. Altogether 347 victims of violence were identified (among them 109 victims of "public violence", 59 victims of domestic violence, and 179 cases that could not be allocated clearly). This results in a quota of 4.9% of all patients treated. The average age of the victims was 30.6 years. It was striking that in many cases the anamnesis and documentation were rather fragmentary. CONCLUSION: A very high percentage of victims of violence could be found among the patients needing traumatological treatment. With regard to the fragmentary care there is an enormous need for medical training and interdisciplinary treatment of victims of violence. PMID- 22065377 TI - [Comparative findings of balloon kyphoplasty in patients with vertebral fractures due to osteoporosis, metastases and myeloma]. AB - OBJECTIVE: By evaluations of treatment protocols, the documentation of balloon kyphoplasty regarding efficacy, duration of action and safety should be expanded. In addition, the evaluations should help to clarify the differences in balloon kyphoplasty for patients with vertebral fractures concerning efficacy and safety in relation to the underlying diseases: osteoporosis, bone metastases or myeloma. MATERIAL AND METHODS: In order to reposition the endplates of the vertebrae a balloon was inserted after placement of the working channels. After removal of the balloon, the resulting caverns were filled with PMMA. The radiological and clinical follow-up examinations were carried out over a period of up to 3 years. The clinical and radiological findings before and after treatment at specified visits were transferred to a statistical programme and evaluated. RESULTS: The comparisons of the postoperative results according to the initial diagnosis (metastases: n = 222, osteoporosis: n = 122, myeloma: n = 122) demonstrated significant differences with respect to the cement leakage (14 %, 5 %, 7.5 %), but in all cases without any clinical relevance. The small differences related to the reduction in pain intensity (VAS > 50 mm in each group) after surgery were up to 12 months with no clinical significance. Also in the Oswestry score no differences between the 3 groups were registered. In the case of osteoporosis patients, due to the lower starting position a more significant increase of vertebral body height could be achieved by the kyphoplasty than in the comparison groups of patients with metastases or myeloma (? 3.1 mm vs. 0.4-0.5 mm; P < 0.001). Consequently, the kyphosis angle decreased in the osteoporotic group also more strongly than in the comparison groups. CONCLUSIONS: It is evident that the pain relief in the vast majority of cases started immediately after surgery. Additionally, a significant improvement in functioning (Oswestry score) was registered. Both clinical parameters - as far as they could be checked - showed a steady degree of improvement over a period of at least 3 years. This comparative analysis led to the conclusion that balloon kyphoplasty can be successfully applied indiscriminately in patients with vertebral fractures as a result of osteoporosis and also to fractures associated with bone metastases or with myeloma. PMID- 22065378 TI - Characterization and optimization of a simple, repeatable system for the long term in vitro culture of aligned myotubes in 3D. AB - Increased recent research activity in exercise physiology has dramatically improved our understanding of skeletal muscle development and physiology in both health and disease. Advances in bioengineering have enabled the development of biomimetic 3D in vitro models of skeletal muscle which have the potential to further advance our understanding of the fundamental processes that underpin muscle physiology. As the principle structural protein of the extracellular matrix, collagen-based matrices are popular tools for the creation of such 3D models but the custom nature of many reported systems has precluded their more widespread adoption. Here we present a simple, reproducible iteration of an established 3D in vitro model of skeletal muscle, demonstrating both the high levels of reproducibility possible in this system and the improved cellular architecture of such constructs over standard 2D cell culture techniques. We have used primary rat muscle cells to validate this simple model and generate comparable data to conventional established cell culture techniques. We have optimized culture parameters for these cells which should provide a template in this 3D system for using muscle cells derived from other donor species and cell lines. PMID- 22065379 TI - Di-n-propyl 4,4'-dihy-droxy-3,3'-{[(3aRS,7aRS)-2,3,3a,4,5,6,7,7a-octa-hydro-1H benzimidazole-1,3-di-yl]bis-(methyl-ene)}dibenzoate. AB - The title compound, C(29)H(38)N(2)O(6), was prepared as model for studying intra molecular hydrogen-bonding inter-actions. Mol-ecules of the title compound are located on a crystallographic twofold rotation axis, which passes through the C atom linked to the two N atoms on the imidazolidine ring. The mol-ecular structure shows the existence of two intra-molecular O-H?N hydrogen-bonding inter actions between the two N atoms of the imidazolidine moiety and the hy-droxy groups in the aromatic rings. The crystal structure shows the strain of ring fusion in the perhydro-benzimidazole moiety according to the endocyclic bond angles and the torsion angles, which evidence a puckering of the cyclo-hexane ring with respect to normal tetra-hedral bond angles in an ideal chair conformation. PMID- 22065380 TI - Facilitating the pickup of individual DNA molecules by AFM nanomanipulation with tips mechanically worn on bare mica. AB - The tip is one of the critical factors to improve the efficiency in picking up individual DNA molecules from solid substrates based on atomic force microscope (AFM) nanomanipulation. We found that wearing AFM tips on certain solid substrates in advance to nanomanipulation operation would largely improve the pickup efficiency, which was ascribed to the increasing affinity of the tip to the DNA molecules along with the increase of the tip radius after wearing. It was demonstrated that bare mica was superior to APTES-modified mica to keep the tip clean while wearing, which was crucial for DNA pickup during AFM nanomanipulation. PMID- 22065381 TI - Current role of interventions in metastatic kidney tumors: single center experience. AB - This study on the treatment of kidney tumor metastases aims to expose our experience in different interventional therapies for renal cell carcinomas metastasis in different organs, broaching their complications and comparing our results with the literature. In the last 5 years, after informed consent, 22 patients with metastatic kidney tumors were enrolled in this retrospective observational study. According to lesion sites, different interventional procedures may be performed: RFA for pancreas, lung, adrenal gland and liver lesions; TAE and RFA for bone lesions and IVC filter positioning for thrombosis of renal vein. There were mainly satisfactory results: complete necrosis of pancreas, lung and adrenal gland metastasis with a technical success rate of 100%; after TAE and RFA of bone lesions, an acceptable blood loss was registered during surgical intervention; no recurrences after liver metastasis ablation were observed in a period of 3 months; positioning of IVC filter was technically correct in 100% of patients; few complications, such as diffuse abdominal pain for pancreas, pneumothorax in the lung RCC metastasis and a post-RFA syndrome for the adrenal. There was a nodular recurrence along the ablation margin in one liver RCC metastasis. Inclusion criteria were relatively strict and only 22 patients were included in this study. The follow-up has been relatively short to date, so we are not certain of the long-term results, though these are comparable to those found in literature. It is possible to conclude that Interventional radiology plays an important role in RCC metastasis treatment, if we have few complications and improved outcomes. PMID- 22065382 TI - Central anticholinergic syndrome presenting as akinetic mutism. AB - A case of central anticholinergic syndrome due to overdosage of trihexyphenidyl hydrochloride presenting as septal akinetic mutism with unequally dilated pupils is discussed in reference to similar presentation in animals and possible clinical application. PMID- 22065383 TI - Time and number: the privileged status of small values in the brain. PMID- 22065384 TI - Microarray-based identification of aminopeptidase N target genes in keratinocyte conditioned medium-stimulated dermal fibroblasts. AB - Of the many processes that affect the outcome of wound repair, epidermal-dermal interactions are essential to extracellular matrix (ECM) remodeling and in particular, soluble factors released by keratinocytes are known to have a direct impact on the production of ECM by dermal fibroblasts. Aminopeptidase N (APN) has recently been proposed as a cell-surface receptor for stratifin and is responsible for the stratifin-mediated matrix metalloproteinase-1 (MMP-1) upregulation in fibroblasts. The present study examines whether modulation of APN gene expression has any impact on the fibroblast ECM gene expression profile. The result reveals that in the presence of keratinocyte-derived soluble factors, transient knockdown of APN in dermal fibroblasts affects the expression of key ECM components such as fibronectin, tenascin-C, MMP-1, MMP-3, and MMP-12. The regulatory effects of APN on fibronectin and selective MMPs appear to be associated with receptor-mediated signal transduction independently of its peptidase activity. On the contrary, inhibition of the APN enzymatic activity by bestatin significantly reduces the tenascin-C expression and enhances the contraction of fibroblast-populated collagen gel, suggesting an activity dependent regulation of fibroblast contractility by APN. The overall effects of APN on the expression of fibronectin, tenascin-C, and MMPs in fibroblasts propose an important role for APN in the regulation of keratinocyte-mediated ECM remodeling and fibroblast contractile activity. PMID- 22065385 TI - Trends in biomedical engineering: focus on Regenerative Medicine. AB - Regenerative medicine is a critical frontier in biomedical and clinical research. The major progresses in the last few years were driven by a strong clinical need which could benefit from regenerative medicine outcomes for the treatment of a large number of conditions including birth defects, degenerative and neoplastic diseases, and traumatic injuries. Regenerative medicine applies the principles of engineering and life sciences to enhance the comprehension of the fundamental biological mechanisms underlying the structure-function relationships in physiologic and pathologic tissues and to accomplish alternative strategies for developing in vitro biological substitutes which are able to restore, maintain, or improve tissue, and organ function. This paper reviews selected approaches currently being investigated at Politecnico di Milano in the field of regenerative medicine. Specific tissue-oriented topics are divided in three sections according to each developmental stage: in vitro study, pre-clinical study, and clinical application. In vitro studies investigate the basic phenomena related to gene delivery, stem cell behavior, tissue regeneration, and to explore dynamic culture potentiality in different applications: cardiac and skeletal muscle, cartilage, hematopoietic system, peripheral nerve, and gene delivery. Specific fields of regenerative medicine, i.e., bone, blood vessels, and ligaments engineering have already reached the preclinical stage providing promising insights for further research towards clinical applications. The translation of the results obtained during in vitro and preclinical steps into clinical organ replacement is a very challenging issue, which can offer a valid alternative to fight morbidity, organ shortage, and ethical-social problems associated with allotransplantation as shown in the clinical case reported in this review. PMID- 22065386 TI - Trends in biomedical engineering: focus on Smart Bio-Materials and Drug Delivery. AB - The present article reviews on different research lines, namely: drug and gene delivery, surface modification/modeling, design of advanced materials (shape memory polymers and biodegradable stents), presently developed at Politecnico di Milano, Italy. For gene delivery, non-viral polycationic-branched polyethylenimine (b-PEI) polyplexes are coated with pectin, an anionic polysaccharide, to enhance the polyplex stability and decrease b-PEI cytotoxicity. Perfluorinated materials, specifically perfluoroether, and perfluoro-polyether fluids are proposed as ultrasound contrast agents and smart agents for drug delivery. Non-fouling, self-assembled PEG-based monolayers are developed on titanium surfaces with the aim of drastically reducing cariogenic bacteria adhesion on dental implants. Femtosecond laser microfabrication is used for selectively and spatially tuning the wettability of polymeric biomaterials and the effects of femtosecond laser ablation on the surface properties of polymethylmethacrylate are studied. Innovative functionally graded Alumina-Ti coatings for wear resistant articulating surfaces are deposited with PLD and characterized by means of a combined experimental and computational approach. Protein adsorption on biomaterials surfaces with an unlike wettability and surface-modification induced by pre-adsorbed proteins are studied by atomistic computer simulations. A study was performed on the fabrication of porous Shape Memory Polymeric structures and on the assessment of their potential application in minimally invasive surgical procedures. A model of magnesium (alloys) degradation, in a finite element framework analysis, and a bottom-up multiscale analysis for modeling the degradation mechanism of PLA matrices was developed, with the aim of providing valuable tools for the design of bioresorbable stents. PMID- 22065387 TI - Trends in biomedical engineering: focus on Genomics and Proteomics. AB - Genomics is the study of an organism's genome aimed at the functional specification of the different parts of the sequence that comprise the blueprint of the living cell to unveil the mechanisms of the physiology of the cell and its basic, developmental, and tissue-specific processes. Proteomics is the comprehensive study of the executive molecules of the cell coded by the genome, further raising the level of complexity, because of the large amplification in the number, going from genes to proteins, and to the sophisticated structural and functional characterization of protein products, which confer specific biochemical properties. While continuous progress in technology provides new experimental solutions to study and measure the behavior of genes and proteins in the cell, the analysis and the management of biological data cannot be uncoupled from the use of mathematics, statistics, and informatics disciplines that play a key role in modern molecular biology.Together, genomics and proteomics, meant as complementary approaches, delineate the framework of modern molecular medicine, where the knowledge of the functional mechanisms on a subcellular scale, both under physiologic and pathologic conditions, may lead to an improvement in diagnosis, therapy, and drug development. PMID- 22065388 TI - Trends in biomedical engineering: focus on Patient Specific Modeling and Life Support Systems. AB - Over the last twenty years major advancements have taken place in the design of medical devices and personalized therapies. They have paralleled the impressive evolution of three-dimensional, non invasive, medical imaging techniques and have been continuously fuelled by increasing computing power and the emergence of novel and sophisticated software tools. This paper aims to showcase a number of major contributions to the advancements of modeling of surgical and interventional procedures and to the design of life support systems. The selected examples will span from pediatric cardiac surgery procedures to valve and ventricle repair techniques, from stent design and endovascular procedures to life support systems and innovative ventilation techniques. PMID- 22065389 TI - Biomechanics of implant-tooth supported prostheses: effects of mesiodistal implant angulation and mode of prosthesis connection. AB - PURPOSE: The purpose of this study was to explore the effects of implant angulation and its possible influence on prosthetic connection as regards implant/tooth strains in a combined implant and natural tooth abutment fixed partial denture. METHODS: A natural tooth was embedded between vertically-aligned and 17 degrees angulated implants in a polymethyl methacrylate acrylic resin model. Three designs (Group 1: tooth and vertically-aligned implant; Group 2: tooth and 17 degrees angulated implant, Group 3: tooth and vertically-aligned implant having a different prosthetic connection to Group 1) of tooth-implant supported prostheses (n=4) were fabricated. Strain gauges were bonded on the prostheses and on the approximal sides of the natural tooth abutment and implants. Once the test fixed partial dentures were seated, a static load of 150 N was applied to each prosthesis. During testing, strain-gauge signals were digitalized by a data acquisition system and this signal was stored and assessed with corresponding software at a sample rate of 10 KHz. RESULTS: The data were then evaluated using Mann-Whitney U and Kruskal Wallis tests at 95% confidence level. Mesiodistal tilting of implants increased peri-implant strains in implant tooth supported prostheses during torque-tightening and under load. The mode of prosthesis connection may affect strains within the prosthesis and natural tooth abutments, although its impact under static loading conditions seems negligible. CONCLUSIONS: This investigation suggests that mesiodistal tilting of implants may have a biomechanical effect in tooth-implant supported prostheses. PMID- 22065390 TI - Rheological properties of cross-linked hyaluronic acid dermal fillers. AB - AIM: Ha based dermal fillers in recent years aroused big interest in the area of cosmetic surgery for the rejuvenation of the dermis. There is not a ideal dermal filler (DF) for all applications and in commerce there are many types of DF that differ for their chemical-physical properties. So the aim of this paper is to correlate the rheological and physical properties of different DF to their clinical effectiveness. MATERIALS AND METHODS: In this frame the samples have been subjected to oscillation dynamic rheological and steady shear measurements. RESULTS: Our results demonstrate that the viscoelastic properties of different DF varie strongly also considering fillers of the same family. Furthermore it was found that the materials physical properties influence significantly the performance of dermal filler. In particular the clinical data appear to correlate with the concentration of the polymer and with the product between the concentration and the percent elasticity, so these should be crucial parameters for the clinical performance of DF. CONCLUSION: So rheological data can be a tool to have an indication on the efficacy and longevity of DF but it has to be considered that production technology, in-vivo-conditions, injector skills and experience influence them also significantly. PMID- 22065391 TI - Influence of metal ions on human lymphocytes and the generation of titanium specific T-lymphocytes. AB - BACKGROUND: There is mounting evidence to suggest the involvement of the immune system by means of activation by metal ions released via biocorrosion, in the pathophysiologic mechanisms of aseptic loosening of orthopedic implants. However, the detailed mechanisms of how metal ions become antigenic and are presented to T lymphocytes, in addition to how the local inflammatory response is driven, remain to be investigated. METHODS: Human T-lymphocytes were cultured in the presence of a variety of metal ions before investigating functional and phenotypic changes using flow cytometric analysis. Additionally, human monocyte-derived dendritic cells (mDC) loaded with metal ions were used as antigen-presenting cells and incubated with naive T-lymphocytes with the aim of generating titanium-specific T lymphocytes. RESULTS: Using an autologous in vitro model, with mDC treated with Titanium (IV), we were able to induce Titanium (IV)-specific T-lymphocytes. These T-lymphocytes responded in a dose-related manner to Titanium (IV), while they did not cross-react with Titanium (III) or other metal ions, indicating that the new antigenic peptide complexes formed by Titanium (IV) are highly specific. CONCLUSION: This study showed that mDC exposed to Titanium (IV) are able to induce the generation of Titanium (IV)-specific T-lymphocytes, demonstrating the strong and specific antigenicity of Titanium (IV) ions released by biocorrosion. PMID- 22065392 TI - Effects of nonenzymatic glycation on mechanical properties of demineralized bone matrix under compression. AB - PURPOSE: Effects of in vitro induced nonenzymatic glycation of bone collagen on stiffness and fracture of demineralized bone matrix in unconfined compression were investigated. MATERIAL AND METHODS: Regular specimens from mid-shaft of bovine femur were grouped in pairs. One sample (R) from each pair was incubated in ribose solution, control samples (C) were incubated in a buffer solution. Samples were then demineralized in formic acid. Demineralized samples were axially compressed to failure (0.033/s). Direction of compression was along the longitudinal axis of femur (L) or perpendicular (transverse) to that (T). Mechanical behavior of demineralized samples was characterized in terms of secant modulus, stress, and strain at fracture and work to failure. The development of damage was examined in terms of acoustic emission (AE) signal recorded during loading. RESULTS: In L direction, strain at fracture following glycation was lower than in the controls (p=0.038); secant modulus and ultimate stress were not significantly different in R and C. In the transverse direction, strain at fracture in R was higher than in C (p=0.053), as well as work to failure (p=0.020). Anisotropy of bone matrix, defined in terms of a ratio of the parameters in two perpendicular directions, decreased markedly in ribosylated samples. Both the number of AE events and cumulative AE energy during deformation were significantly higher in ribosylated samples than in the control for both directions of compression. CONCLUSION: The study demonstrated that nonenzymatic glycation plays a significant role in modifying organic matrix properties in cortical bone. PMID- 22065393 TI - Technical features and criteria in designing fiber-reinforced composite materials: from the aerospace and aeronautical field to biomedical applications. AB - Polymer-based composite materials are ideal for applications where high stiffness to-weight and strength-to-weight ratios are required. From aerospace and aeronautical field to biomedical applications, fiber-reinforced polymers have replaced metals, thus emerging as an interesting alternative. As widely reported, the mechanical behavior of the composite materials involves investigation on micro- and macro-scale, taking into consideration micromechanics, macromechanics and lamination theory. Clinical situations often require repairing connective tissues and the use of composite materials may be suitable for these applications because of the possibility to design tissue substitutes or implants with the required mechanical properties. Accordingly, this review aims at stressing the importance of fiber-reinforced composite materials to make advanced and biomimetic prostheses with tailored mechanical properties, starting from the basic principle design, technologies, and a brief overview of composites applications in several fields. Fiber-reinforced composite materials for artificial tendons, ligaments, and intervertebral discs, as well as for hip stems and mandible models will be reviewed, highlighting the possibility to mimic the mechanical properties of the soft and hard tissues that they replace. PMID- 22065394 TI - (E)-1-(4-Chloro-benzyl-idene)-2-phenyl-hydrazine. AB - The asymmetric unit of the title compound, C(13)H(11)ClN(2), contains two geometrically distinct mol-ecules; one mol-ecule is close to planar [dihedral angle between the aromatic rings = 2.44 (18) degrees ] and the other is twisted about the linking hydrazide group [dihedral angle = 14.08 (19) degrees ]. In the crystal, the N-H groups do not form hydrogen bonds and the mol-ecules are linked by weak C-H?pi inter-actions. PMID- 22065396 TI - Aqua-{6,6'-dieth-oxy-2,2'-[ethane-1,2-diyl-bis(nitrilo-methanylyl-idene)]diphen olato}zinc. AB - The mononuclear zinc title complex, [Zn(C(20)H(22)N(2)O(4))(H(2)O)], was obtained by the reaction of 3-eth-oxy-salicyl-aldehyde, ethane-1,2-diamine, and zinc acetate in methanol. The Zn atom is five-coordinated by two phenolate O and two imine N atoms of the tetradentate Schiff base ligand and by one water O atom, forming a square-pyramidal geometry. In the crystal, pairs of mol-ecules are linked via inter-molecular O-H?O hydrogen bonds, forming dimers. PMID- 22065397 TI - Adolescent Sexual Assault and the Medical and Nonmedical Use of Prescription Medication. AB - Previous research has documented an association between sexual victimization and prescription medication use among adults. The purpose of this study was to determine whether such a relationship was present for adolescent girls when considering sexual victimization by a peer and the use of four drug classes for medical and nonmedical reasons. The study was based on a secondary analysis of a cross-sectional Web-based, self-administered survey of female students from a middle and high school (n = 490). As predicted, sexual victimization increased the likelihood of non-medical prescription medication use of opioid analgesics and sedative medication, although these relationships varied based on the severity of sexual assault. Findings are discussed in light the importance of increasing awareness among health professionals, researchers, and the wider community of the increased risk for prescription medication abuse among adolescent girls who have a history of sexual violence. PMID- 22065398 TI - Self-etching adhesive on intact enamel, with and without pre-etching. AB - OBJECTIVE: Bond strengths of composite resin to enamel using self-etch adhesive (SEA) Clearfil SE bond system on intact enamel and enamel pre-etched with phosphoric acid were compared. The objective was to determine if the pre-etching would increase the bond strengths of the SEA systems to intact enamel and to evaluate the effect of pre-etching on bond formation of self-etch adhesives on intact enamel. MATERIALS AND METHOD: Labial surfaces of 40 caries free permanent upper central and lateral incisors were cleaned, sectioned of their roots. All specimens were mounted on acrylic block and divided randomly into four groups. In two groups the application of self-etch adhesive, Clearfil SE bond was carried as per manufacturer's instructions, composite cylinders were built, whereas in the other two groups, 37% phosphoric acid etching was done before the application of self-etching adhesives. Then the resin tags were analyzed using scanning electron microscope and shear bond strength was measured using Instron universal testing machine. RESULTS: When phosphoric acid was used, there was significant increase in the depth of penetration of resin tags and in the Shear Bond Strength of composite to enamel. CONCLUSION: The results indicate that out of both treatment groups, pre-etching the intact enamel with 37% phosphoric acid resulted in formation of longer resin tags and higher depth of penetration of resin tags of the Clearfil SE bond, and attaining higher bond strength of the Clearfil SE bond to intact enamel. PMID- 22065399 TI - Development and application of whole-sediment toxicity test using immobilized freshwater microalgae Pseudokirchneriella subcapitata. AB - A method for a whole-sediment toxicity test using alginate immobilized microalgae Pseudokirchneriella subcapitata was developed using spiked sediments and applied to contaminated field sediment samples. For method development, a growth inhibition test (72 h) with algal beads was conducted for the sediments spiked with Cu or diuron. The method was validated by determining dose-response relationships for Cu and diuron in both fine-grained and coarse-grained sediments. The results of a spiked sediment toxicity test suggested that sediment particle size distribution (clay content) had a significant effect on the growth of P. subcapitata. The developed method using immobilized microalgae P. subcapitata beads was applied successfully in the toxicity test and toxicity identification evaluation (TIE) for the four field sediment samples. After a series of extractions with 0.01 M CaCl(2) solution, acetone, and dichloromethane, the extracted sediment, which was shown to be nontoxic to algae, was used as the control and diluent for the same sediment in the whole-sediment toxicity test. The results showed that all investigated field sediment samples were found to be toxic to the immobilized algae P. subcapitata, with their median effective concentration (EC50) values ranging from 41.4 to 79.0% after 72 h exposure. In the whole sediment TIE, growth of P. subcapitata was improved to varying degrees after adding zeolite, resin, or activated charcoal, suggesting different contributions to toxicity from ammonia, metals, and organic contaminants in the tested sediments. PMID- 22065400 TI - A randomized, crossover, placebo- and moxifloxacin-controlled study to evaluate the effects of bosutinib (SKI-606), a dual Src/Abl tyrosine kinase inhibitor, on cardiac repolarization in healthy adult subjects. AB - Effects of therapeutic and supratherapeutic concentrations of bosutinib, a dual Src/Abl tyrosine kinase inhibitor, on the corrected QT interval (QTc) in 60 healthy adults were assessed, according to ICH-E14 guidelines, in this 2-part, randomized, single-dose, double-blind, crossover, placebo- and open-label moxifloxacin-controlled study. Subjects received placebo, moxifloxacin and bosutinib 500 mg with food (therapeutic) in Part 1. In Part 2, subjects received placebo and bosutinib 500 mg plus ketoconazole (supratherapeutic). ANOVA compared baseline-adjusted QTc for bosutinib with placebo; and bosutinib plus ketoconazole with placebo plus ketoconazole. Primary endpoint was population-specific QT correction (QTcN). Secondary endpoints were Bazett QT correction (QTcB), Fridericia's formula QT correction (QTcF) and individual QT correction (QTcI). Upper bounds for 90% confidence intervals were <10 msec for the mean change in QTcN from placebo at all postdose time points, suggesting that mean therapeutic exposures (C(max) , 114 ng/mL; AUC, 2,330 ng . h/mL) and mean supratherapeutic exposures (C(max) , 326 ng/mL; AUC, 15,200 ng . h/mL) were not associated with QTc changes. Similar results were obtained for QTcB, QTcF and QTcI. No clinically relevant pharmacokinetic/pharmacodynamic relationship was observed between bosutinib concentrations and QTc. No subjects had QTcB, QTcF, QTcI or QTcN >450 msec or change from baseline >30 msec. In summary, therapeutic and supratherapeutic bosutinib exposures are not associated with QTc prolongation in healthy adults. PMID- 22065402 TI - 3,3'-Dinitro-bis-phenol A. AB - THE TITLE COMPOUND [SYSTEMATIC NAME: 2,2'-dinitro-4,4'-(propane-2,2-di yl)diphenol], C(15)H(14)N(2)O(6), crystallizes with two mol-ecules in the asymmetric unit. Both have a trans conformation for their OH groups, and in each, the two aromatic rings are nearly orthogonal, with dihedral angles of 88.30 (3) and 89.62 (2) degrees . The nitro groups are nearly in the planes of their attached benzene rings, with C-C-N-O torsion angles in the range 1.21 (17)-4.06 (17) degrees , and they each accept an intra-molecular O-H?O hydrogen bond from their adjacent OH groups. One of the OH groups also forms a weak inter-molecular O-H?O hydrogen bond. PMID- 22065403 TI - (E)-N'-(5-Bromo-2-meth-oxy-benzyl-idene)-2-chloro-benzohydrazide. AB - In the title compound, C(15)H(12)BrClN(2)O(2), the dihedral angle between the two substituted aromatic rings is 77.8 (3) degrees . The mol-ecule exists in a trans conformation with respect to the methyl-idene unit. In the crystal structure, inversion dimers linked by pairs of N-H?O hydrogen bonds generate R(2) (8)(8) loops. PMID- 22065404 TI - 1-[(E)-4-(Phenyl-diazen-yl)phen-yl]-3-pyrroline-2,5-dione. AB - The title compound, C(16)H(11)N(3)O(2), displays a trans configuration with respect to the azo group. The mol-ecule is non-planar; the maleimide ring forms a dihedral angle of 42.35 (4) degrees with the benzene ring bonded to its N atom and the mean plane of this benzene ring is rotated by 21.46 (8) degrees with respect to the azo group mean plane, which, in turn, forms a dihedral angle of 24.48 (7) degrees with the 'terminal' benzene ring. Mol-ecules in the crystal are pi-pi stacked along the [100] direction with a mean inter-planar distance of 3.857 (1) A. In addition, C-H?O inter-actions link them into double layers parallel to the ac plane. PMID- 22065405 TI - The role of the characteristics of humic substances in binding with benzo[h]quinoline. AB - The binding constants (K(DOC)) of the mixture of benzo[h]quinoline and its protonated analog, benzo[h]quinolinium, to four types of humic substances obtained from the International Humic Substances Society were determined by the fluorescence quenching method. A simple mixing model was used to eliminate the fluorescent interference from the minor analog in the solution and to deduce K(mix), which represents the overall binding as the sum of that for the individual analogs. The characteristics of humic substances, especially their hydrophobicity and aromaticity, established by principal component analysis of structural and elemental compositions, were the main determinants of the binding affinity with both benzo[h]quinoline and benzo[h]quinolinium (K(BQ) and K (BQH+) across a range of pH values. The strongest overall affinity of benzo[h]quinoline for humic substances is observed near pH 4 and with more hydrophobic humic substances, which suggests possible choices in attempts at remediation of benzo[h]quinoline containing particles with humic substances. PMID- 22065406 TI - Pathways for water loss from doubly protonated peptides containing serine or threonine. AB - The doubly-protonated peptides Ala-Ala-Xaa-Ala-Ala-Ala-Arg show extensive loss of H(2)O when Xaa = Ser or Thr. Using quasi-MS(3) techniques the fragmentation reactions of the [M + 2H - H(2)O](+2) ions have been studied in detail. For both Ser and Thr, the [M + 2H - H(2)O](+2) ions show three primary fragmentation reactions, elimination of CH(3)CH=NH, elimination of one Ala residue, and elimination of two Ala residues, in all cases forming doubly-charged products. From a study of the further fragmentation of these products, it is concluded that elimination of two Ala residues results in formation of a three-membered aziridine ring by interaction with the adjacent amide function as H(2)O is lost. The elimination of one Ala residue results in formation of a five-membered oxazoline ring through interaction with the N-terminal adjacent carbonyl function as H(2)O is lost. The elimination of CH(3)CH=NH appears to involve formation of an eight-membered ring by interaction with the remote N-terminal carbonyl function as H(2)O is lost. However, this initial structure undergoes rearrangement through interaction with the adjacent C-terminal carbonyl function prior to further fragmentation. The [MH - H(2)O](+) ion of Ala-Ala-Ser-Ala-Ala Ala also shows elimination of CH(3)CH=NH, one Ala residue and two Ala residues. PMID- 22065407 TI - Aqua-[4-(hy-droxy-imino-meth-yl)pyridine-kappaN](imino-diacetato kappaO,N,O')copper(II). AB - In the title complex, [Cu(C(4)H(5)NO(4))(C(6)H(6)N(2)O)(H(2)O)], conventionally abbreviated Cu(IDA)(4-OXPy)(H(2)O), where IDA is imino-diacetate and 4-OXPy is 4 (hy-droxy-imino-meth-yl)pyridine, the Cu(II) atom exhibits a distorted square pyramidal coordination geometry, which is constructed from two O atoms and one N atom from a IDA ligand, one N atom from 4-OXPy ligand and one O atom from water. This mol-ecule looks like a space shuttle, the IDA ligand is its empennage (tail), and the 4-OXPy ligand is its airframe. The complexes are linked into two dimensional supra-molecular layers parallel to (100) by three pairs of O-H?O hydrogen bonds. Two pairs of N-H?O hydrogen bonds further connect these supra molecular layers, forming a three-dimensional supra-molecular network. PMID- 22065408 TI - 2,4-Dichloro-N-(3,4-dimethyl-phen-yl)benzene-sulfonamide. AB - In the title compound, C(14)H(13)Cl(2)NO(2)S, the C-SO(2)-NH-C torsion angle is 60.84 (18). The sulfonyl and the aniline benzene rings are tilted relative to each other by 66.4 (1) degrees . The crystal structure features inversion-related dimers linked by pairs of N-H?O hydrogen bonds. PMID- 22065409 TI - Representation of non-spatial and spatial information in the lateral entorhinal cortex. AB - Some theories of memory propose that the hippocampus integrates the individual items and events of experience within a contextual or spatial framework. The hippocampus receives cortical input from two major pathways: the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). During exploration in an open field, the firing fields of MEC grid cells form a periodically repeating, triangular array. In contrast, LEC neurons show little spatial selectivity, and it has been proposed that the LEC may provide non spatial input to the hippocampus. Here, we recorded MEC and LEC neurons while rats explored an open field that contained discrete objects. LEC cells fired selectively at locations relative to the objects, whereas MEC cells were weakly influenced by the objects. These results provide the first direct demonstration of a double dissociation between LEC and MEC inputs to the hippocampus under conditions of exploration typically used to study hippocampal place cells. PMID- 22065410 TI - 5-(4-Fluoro-phen-yl)-2-methyl-3-methyl-sulfinyl-1-benzofuran. AB - In the title compound, C(16)H(13)FO(2)S, the 4-fluoro-phenyl ring makes a dihedral angle of 38.75 (8) degrees with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds. PMID- 22065411 TI - (2,6-Difluoro-phen-yl)(4-methyl-piperidin-1-yl)methanone. AB - In the title compound, C(13)H(15)F(2)NO, the piperidine ring adopts a chair conformation. The dihedral angle between the least-squares plane of the piperidine ring and the benzene ring is 48.75 (7) degrees . In the crystal structure, the mol-ecules are connected via C-H?O hydrogen bonds, forming a zigzag chain along the b axis. PMID- 22065412 TI - 4-Chloro-N-(2,3-dimethyl-phen-yl)-2-methyl-benzene-sulfonamide. AB - The asymmetric unit of the title compound, C(15)H(16)ClNO(2)S, contains two independent moleules. The conformation of the N-H bonds are anti to the ortho methyl groups in the sulfonyl benzene rings of both the mol-ecules, while the N-H bonds are anti to the ortho- and meta-methyl groups in the aniline ring of one of the mol-ecules and syn in the other. Furthermore, the torsion angles of the C SO(2)-NH-C segments in the two mol-ecules of are -66.8 (3) and 70.3 (3) degrees . The sulfonyl and the aniline benzene rings are oriented at angles of 44.1 (1) and 39.7 (1) degrees in the two mol-ecules. In the crystal, pairs of N-H?O hydrogen bonds link the mol-ecules into dimers. PMID- 22065413 TI - (E)-N'-(5-Bromo-2-hy-droxy-3-meth-oxy-benzyl-idene)-1H-indole-3-carbo-hydrazide. AB - There are three independent mol-eculesi n the asymmetric unit of the title compound, C(18)H(16)BrN(3)O(3), in which the dihedral angles between the indole and benzene rings are 76.9 (2), 4.9 (2), and 70.9 (2) degrees . All three mol ecules exist in a trans configuration with respect to the methyl-idene units. In each mol-ecule, there is one intra-molecular O-H?N hydrogen bond. In the crystal, N-H?O hydrogen bonds occur. PMID- 22065414 TI - Does reconsolidation occur in humans: a reply. PMID- 22065415 TI - trans-Diaqua-bis-(dl-valinato-kappaN,O)nickel(II). AB - In the title complex, [Ni(C(5)H(9)NO(2))(2)(H(2)O)(2)], the Ni(II) atom, located on a centre of inversion, is trans-coordinated by two O atoms and two N atoms from d-bidentate valine and l-bidentate valine ligands and two water O atoms in an octa-hedral geometry. In the crystal, the discrete mononuclear units are linked into a three-dimensional network via O-H?O and N-H?O hydrogen bonds. C-H?O inter-actions are also observed. PMID- 22065416 TI - 2,2'-[1,5-Bis(4-amino-phen-yl)-1,5-dihydro-benzo[1,2-d;4,5-d']diimidazole-2,6-di yl]diphenol. AB - The title mol-ecule, C(32)H(24)N(6)O(2), has a crystallographic inversion centre in the middle of the benzodiimidazole core. It exists as the enol-imine tautomeric form and exhibits a strong intra-molecular O-H?N hydrogen bond. The dihedral angles between the planes of the 2-hy-droxy-phenyl and 4-amino-phenyl substituents and the plane of the benzodiimidazole unit [12.69 (8) and 84.71 (8) degrees , respectively] differ significantly due to steric reasons. In the crystal, mol-ecules are linked by C-H?pi inter-actions, forming a two-dimensional network. PMID- 22065417 TI - XIAP protects oligodendrocytes against cell death in vitro but has no functional role in toxic demyelination. AB - Oligodendroglial damage and loss are typical characteristics of demyelinating diseases such as multiple sclerosis (MS) and the leukodystrophies. Axonal loss is the underlying cause of permanent neurological deficits in MS and it is thought to arise from a combination of immune-mediated axonal damage and the loss of trophic support to axons from myelin sheaths after demyelination. Prevention of oligodendroglial damage or death and demyelination are therefore attractive neuroprotective treatment strategies. However, a better understanding of mechanisms leading to oligodendroglial damage and demyelination is a prerequisite for the development of such treatment options. Here, we demonstrate that X-linked inhibitor of apoptosis (XIAP), the most potent member of the inhibitor of apoptosis proteins (IAP) family is expressed in oligodendrocytes in vivo and in vitro. Increased expression of XIAP is associated with protection against selected cell death pathways, whereas decreased expression increases oligodendroglial cell death in vitro. However, lack of XIAP does not modulate oligodendroglial cell death in toxic demyelination in vivo. PMID- 22065419 TI - The response of diatom central carbon metabolism to nitrogen starvation is different from that of green algae and higher plants. AB - The availability of nitrogen varies greatly in the ocean and limits primary productivity over large areas. Diatoms, a group of phytoplankton that are responsible for about 20% of global carbon fixation, respond rapidly to influxes of nitrate and are highly successful in upwelling regions. Although recent diatom genome projects have highlighted clues to the success of this group, very little is known about their adaptive response to changing environmental conditions. Here, we compare the proteome of the marine diatom Thalassiosira pseudonana (CCMP 1335) at the onset of nitrogen starvation with that of nitrogen-replete cells using two-dimensional gel electrophoresis. In total, 3,310 protein spots were distinguishable, and we identified 42 proteins increasing and 23 decreasing in abundance (greater than 1.5-fold change; P < 0.005). Proteins involved in the metabolism of nitrogen, amino acids, proteins, and carbohydrates, photosynthesis, and chlorophyll biosynthesis were represented. Comparison of our proteomics data with the transcriptome response of this species under similar growth conditions showed good correlation and provided insight into different levels of response. The T. pseudonana response to nitrogen starvation was also compared with that of the higher plant Arabidopsis (Arabidopsis thaliana), the green alga Chlamydomonas reinhardtii, and the cyanobacterium Prochlorococcus marinus. We have found that the response of diatom carbon metabolism to nitrogen starvation is different from that of other photosynthetic eukaryotes and bears closer resemblance to the response of cyanobacteria. PMID- 22065420 TI - Nucleoid-enriched proteomes in developing plastids and chloroplasts from maize leaves: a new conceptual framework for nucleoid functions. AB - Plastids contain multiple copies of the plastid chromosome, folded together with proteins and RNA into nucleoids. The degree to which components of the plastid gene expression and protein biogenesis machineries are nucleoid associated, and the factors involved in plastid DNA organization, repair, and replication, are poorly understood. To provide a conceptual framework for nucleoid function, we characterized the proteomes of highly enriched nucleoid fractions of proplastids and mature chloroplasts isolated from the maize (Zea mays) leaf base and tip, respectively, using mass spectrometry. Quantitative comparisons with proteomes of unfractionated proplastids and chloroplasts facilitated the determination of nucleoid-enriched proteins. This nucleoid-enriched proteome included proteins involved in DNA replication, organization, and repair as well as transcription, mRNA processing, splicing, and editing. Many proteins of unknown function, including pentatricopeptide repeat (PPR), tetratricopeptide repeat (TPR), DnaJ, and mitochondrial transcription factor (mTERF) domain proteins, were identified. Strikingly, 70S ribosome and ribosome assembly factors were strongly overrepresented in nucleoid fractions, but protein chaperones were not. Our analysis strongly suggests that mRNA processing, splicing, and editing, as well as ribosome assembly, take place in association with the nucleoid, suggesting that these processes occur cotranscriptionally. The plastid developmental state did not dramatically change the nucleoid-enriched proteome but did quantitatively shift the predominating function from RNA metabolism in undeveloped plastids to translation and homeostasis in chloroplasts. This study extends the known maize plastid proteome by hundreds of proteins, including more than 40 PPR and mTERF domain proteins, and provides a resource for targeted studies on plastid gene expression. Details of protein identification and annotation are provided in the Plant Proteome Database. PMID- 22065421 TI - The TOPLESS interactome: a framework for gene repression in Arabidopsis. AB - Transcription factors activate or repress target gene expression or switch between activation and repression. In animals and yeast, Groucho/Tup1 corepressor proteins are recruited by diverse transcription factors to induce context specific transcriptional repression. Two groups of Groucho/Tup1-like corepressors have been described in plants. LEUNIG and LEUNIG_HOMOLOG constitute one group and TOPLESS (TPL) and the four TPL-related (TPR) corepressors form the other. To discover the processes in which TPL and the TPR corepressors operate, high throughput yeast two-hybrid approaches were used to identify interacting proteins. We found that TPL/TPR corepressors predominantly interact directly with specific transcription factors, many of which were previously implicated in transcriptional repression. The interacting transcription factors reveal that the TPL/TPR family has been coopted multiple times to modulate gene expression in diverse processes, including hormone signaling, stress responses, and the control of flowering time, for which we also show biological validation. The interaction data suggest novel mechanisms for the involvement of TPL/TPR corepressors in auxin and jasmonic acid signaling. A number of short repression domain (RD) sequences have previously been identified in Arabidopsis (Arabidopsis thaliana) transcription factors. All known RD sequences were enriched among the TPL/TPR interactors, and novel TPL-RD interactions were identified. We show that the presence of RD sequences is essential for TPL/TPR recruitment. These data provide a framework for TPL/TPR-dependent transcriptional repression. They allow for predictions about new repressive transcription factors, corepressor interactions, and repression mechanisms and identify a wide range of plant processes that utilize TPL/TPR-mediated gene repression. PMID- 22065422 TI - Gravistimulation changes the accumulation pattern of the CsPIN1 auxin efflux facilitator in the endodermis of the transition zone in cucumber seedlings. AB - Cucumber (Cucumis sativus) seedlings grown in a horizontal position develop a specialized protuberance (or peg) on the lower side of the transition zone between the hypocotyl and the root. This occurs by suppressing peg formation on the upper side via a decrease in auxin resulting from a gravitational response. However, the gravity-stimulated mechanism of inducing asymmetric auxin distribution in the transition zone is poorly understood. The gravity-sensing tissue responsible for regulating auxin distribution in the transition zone is thought to be the endodermal cell. To characterize the gravity-stimulated mechanism, the auxin efflux facilitator PIN-FORMED1 (CsPIN1) in the endodermis was identified and the localization of CsPIN1 proteins during the gravimorphogenesis of cucumber seedlings was examined. Immunohistochemical analysis revealed that the accumulation pattern of CsPIN1 protein in the endodermal cells of the transition zone of cucumber seedlings grown horizontally differed from that of plants grown vertically. Gravistimulation for 30 min prompted changes in the accumulation pattern of CsPIN1 protein in the endodermis as well as the asymmetric distribution of auxin in the transition zone. Furthermore, 2,3,5-triiodobenzoic acid inhibited the differential distribution of auxin as well as changes in the accumulation pattern of CsPIN1 in the endodermis of the transition zone during gravistimulation. These results suggest that the altered pattern of CsPIN1 accumulation in the endodermis in response to gravistimulation influences lateral auxin transport through the endodermis, resulting in asymmetric auxin distribution in the transition zone. PMID- 22065423 TI - Two phases of replacement replenish the olfactory ensheathing cell population after injury in postnatal mice. AB - Olfactory ensheathing cells (OECs) support the regeneration of olfactory sensory neurons throughout life, however, it remains unclear how OECs respond to a major injury. We have examined the proliferation and migration of OECs following unilateral bulbectomy in postnatal mice. S100beta-DsRed and OMP-ZsGreen transgenic mice were used to visualize OECs and olfactory neurons, respectively, and we used the thymidine analogue ethynyl deoxyuridine (EdU) to identify cells that were proliferating at the time of administration. Following unilateral bulbectomy, there was an initial phase of OEC proliferation throughout the olfactory pathway with a peak of proliferation occurring 2 to 7 days after the injury. A second phase of proliferation also occurred in which precursors localized within the olfactory mucosa divided to replenish the OEC population. We then tracked the positions of OECs that had proliferated and found that there was a progressive increase in OECs in the cavity for at least 12 to 16 days after injury which could not be accounted for solely by local proliferation of OECs within the cavity. These results suggest that OECs migrated from the peripheral olfactory nerve to populate the mass of cells that filled cavity left by bulbectomy. Our results demonstrate that following injury to the olfactory nervous system, the OEC population is replenished by migration of cells that arise from both local proliferation of OECs throughout the olfactory nerve pathway as well as from precursor cells in the olfactory mucosa. PMID- 22065424 TI - A perception theory in mind-body medicine: guided imagery and mindful meditation as cross-modal adaptation. AB - A new theory of mind-body interaction in healing is proposed based on considerations from the field of perception. It is suggested that the combined effect of visual imagery and mindful meditation on physical healing is simply another example of cross-modal adaptation in perception, much like adaptation to prism-displaced vision. It is argued that psychological interventions produce a conflict between the perceptual modalities of the immune system and vision (or touch), which leads to change in the immune system in order to realign the modalities. It is argued that mind-body interactions do not exist because of higher-order cognitive thoughts or beliefs influencing the body, but instead result from ordinary interactions between lower-level perceptual modalities that function to detect when sensory systems have made an error. The theory helps explain why certain illnesses may be more amenable to mind-body interaction, such as autoimmune conditions in which a sensory system (the immune system) has made an error. It also renders sensible erroneous changes, such as those brought about by "faith healers," as conflicts between modalities that are resolved in favor of the wrong modality. The present view provides one of very few psychological theories of how guided imagery and mindfulness meditation bring about positive physical change. Also discussed are issues of self versus non-self, pain, cancer, body schema, attention, consciousness, and, importantly, developing the concept that the immune system is a rightful perceptual modality. Recognizing mind-body healing as perceptual cross-modal adaptation implies that a century of cross modal perception research is applicable to the immune system. PMID- 22065425 TI - 4,4'-Dibromo-2,2'-[m-phenyl-enebis(nitrilo-methanylyl-idene)]diphenol. AB - The title compound, C(20)H(14)Br(2)N(2)O(2), is a dibasic tetra-dentate Schiff base and reveals intra-molecular O-H?N hydrogen bonds between the hy-droxy O atoms and the imino N atoms. The dihedral angle between the central and terminal benzene rings is 39.7 (1) degrees . In the crystal, the compound is disposed about a crystallographic mirror plane parallel to the ac plane passing through the two central C atoms. The mol-ecules are stacked in columns along the c axis through pi-pi inter-actions, the shortest centroid-centroid distance being 3.872 (3) A. PMID- 22065426 TI - Initial management of and outcome in patients with pneumococcal bacteremia: a retrospective study at a Swiss university hospital, 2003-2009. AB - PURPOSE: The aim of this quality control study was to assess the time to initial diagnostic procedures and the time to the first dose of antibiotics in patients with pneumococcal bacteremia, and to investigate whether the timeliness of these interventions influenced outcome. METHODS: We retrospectively studied patient characteristics, chronological sequence of diagnostic and therapeutic steps, and the course of disease of all patients with pneumococcal bacteremia at a Swiss university hospital between 2003 and 2009, and we analyzed associations between these factors and the length of hospital stay (LOS) and mortality. RESULTS: A total of 102 episodes of pneumococcal bacteremia in 98 patients were analyzed, of whom 15.7% died during hospitalization. The median time (interquartile range [IQR]) to the first antibiotic dose was 4.0 (2.0-5.9) h, and the median times (IQR]) to blood cultures, chest radiograph, lumbar puncture, and brain computed tomography (CT) scan or magnetic resonance imaging (MRI) were 1.4 (0.5-3.3), 2.5 (1.2-4.2), 4.2 (2.7-7.2), and 2.3 (0.6-6.2) h, respectively. The time to diagnostic procedures and therapy were not associated with LOS or death. Risk factors for death in the univariable analysis were: Charlson comorbidity index [odds ratio [OR] (95% confidence interval) per unit increase, 1.3 (1.1-1.6)], neutropenia [OR 10.1 (2.0-51.0)], human immunodeficiency virus (HIV) infection [OR 3.9 (1.1-13.8)], chronic respiratory disease [OR 4.4 (1.2-16.0)], chronic liver disease [OR 3.2 (1.0-9.7)], smoking [OR 3.8 (1.1-13.5)], injection drug use [OR 9.7 (1.5-63.7)], and antibiotic therapy within 6 months before admission [OR 4.0 (1.3-12.5)]. The multivariable analysis revealed age >60 years (P = 0.048) and alcoholism (P = 0.009) as risks for prolonged LOS. CONCLUSIONS: The outcome of pneumococcal bacteremia may be more influenced by patient characteristics than by minor differences in the timeliness of initial diagnostic and therapeutic measures within the first several hours after hospital admission. PMID- 22065427 TI - Anatomy of a nanoscale conduction channel reveals the mechanism of a high performance memristor. AB - By employing a precise method for locating and directly imaging the active switching region in a resistive random access memory (RRAM) device, a nanoscale conducting channel consisting of an amorphous Ta(O) solid solution surrounded by nearly stoichiometric Ta(2) O(5) is observed. Structural and chemical analysis of the channel combined with temperature-dependent transport measurements indicate a unique resistance switching mechanism. PMID- 22065428 TI - Shrink-film configurable multiscale wrinkles for functional alignment of human embryonic stem cells and their cardiac derivatives. AB - A biomimetic substrate for cell-culture is fabricated by plasma treatment of a prestressed thermoplastic shrink film to create tunable multiscaled alignment "wrinkles". Using this substrate, the functional alignment of human embryonic stem cell derived cardiomyocytes is demonstrated. PMID- 22065429 TI - Genome size determination using flow cytometry of propidium iodide-stained nuclei. AB - With the rapid expansion of whole-genome sequencing and other genomic studies in nonmodel -organisms, there is a growing demand for robust and user-friendly methods for estimating eukaryotic genome sizes across a broad range of taxa. Propidium iodide (PI) staining with flow cytometry is a powerful method for genome sizing because it is relatively fast, works with a wide variety of materials, and provides information on a very large number of nuclei. In this method, nuclei are stained with PI, which intercalates into the major groove of DNA. Unknown samples are typically costained with standard nuclei of a known genome size, and the relative fluorescence is used to calculate the genome size of the unknown. PMID- 22065430 TI - Chromosome analysis in invertebrates and vertebrates. AB - The revolution in molecular techniques over the last 30 years detracted from many traditional cytological techniques for examining basic biological problems. One of these casualties is the preparation of karyotypes and analysis of chromosomal structure, behaviour, and variation. Recent technology permitting the full sequencing of organisms has highlighted (but does not replace) the importance of understanding chromosomal constitution and karyotype structure, which underpin genome organisation. This chapter provides simple and straightforward protocols for the preparation of chromosome spreads from animals, and more advanced techniques for cell culture and chromosomal banding and hybridisation. PMID- 22065431 TI - Genomic libraries: I. Construction and screening of fosmid genomic libraries. AB - Large insert genome libraries have been a core resource required to sequence genomes, analyze haplotypes, and aid gene discovery. While next generation sequencing technologies are revolutionizing the field of genomics, traditional genome libraries will still be required for accurate genome assembly. Their utility is also being extended to functional studies for understanding DNA regulatory elements. Here, we present a detailed method for constructing genomic fosmid libraries, testing for common contaminants, gridding the library to nylon membranes, then hybridizing the library membranes with a radiolabeled probe to identify corresponding genomic clones. While this chapter focuses on fosmid libraries, many of these steps can also be applied to bacterial artificial chromosome libraries. PMID- 22065432 TI - Genomic libraries: II. Subcloning, sequencing, and assembling large-insert genomic DNA clones. AB - Sequencing large insert clones to completion is useful for characterizing specific genomic regions, identifying haplotypes, and closing gaps in whole genome sequencing projects. Despite being a standard technique in molecular laboratories, DNA sequencing using the Sanger method can be highly problematic when complex secondary structures or sequence repeats are encountered in genomic clones. Here, we describe methods to isolate DNA from a large insert clone (fosmid or BAC), subclone the sample, and sequence the region to the highest industry standard. Troubleshooting solutions for sequencing difficult templates are discussed. PMID- 22065433 TI - Reduced representation methods for subgenomic enrichment and next-generation sequencing. AB - Several methods have been developed to enrich DNA for subsets of the genome prior to next-generation sequencing. These front-end enrichment strategies provide powerful and cost-effective tools for researchers interested in collecting large scale genomic sequence data. In this review, I provide an overview of both general and targeted reduced representation enrichment strategies that are commonly used in tandem with next-generation sequencing. I focus on several key issues that are likely to be important when deciding which enrichment strategy is most appropriate for a given experiment. Overall, these techniques can enable the collection of large-scale genomic data in diverse species, providing a powerful tool for the study of evolutionary biology. PMID- 22065434 TI - Accessing the transcriptome: how to normalize mRNA pools. AB - As advances in next generation sequencing continue to provide increasing access to the genomics -revolution for research systems having few or no genomic resources, transcriptome sequencing will only increase in importance as a fast and direct means of accessing the genes themselves. However, constructing a comprehensive cDNA library for deep sequencing is very difficult, as highly abundant transcripts hamper de novo identification of low-expressed genes, and genes expressed only under very specific conditions will remain elusive. The reduction of variance in gene expression levels to within a tenfold range of differences by cDNA normalization provides an important means of allocating sequencing across a greater fraction of genes, directly translating into a more even coverage across genes. Here, we outline two different normalization methods, addressing many of the important issues we think need consideration when going from RNA isolation to the cDNA material required for sequencing. This will provide coding gene information across thousands of genes from any organism, providing rapid insights into topics such as gene family member identification and genetic variation that may be associated with a studied phenotype. PMID- 22065435 TI - Transcriptome sequencing goals, assembly, and assessment. AB - Transcriptome sequencing provides quick, direct access to the mRNA. With this information, one can design primers for PCR of thousands of different genes, SNP markers, probes for microarrays and qPCR, or just use the sequence data itself in comparative studies. Transcriptome sequencing, while getting cheaper, is still an expensive endeavor, with an examination of data quality and its assembly infrequently performed in depth. Here, we outline many of the important issues we think need consideration when starting a transcriptome sequencing project. We also walk the reader through a detailed analysis of an example transcriptome dataset, highlighting the importance of both within-dataset analysis and comparative inferences. Our hope is that with greater attention focused upon assessing assembly performance, advances in transcriptome assembly will increase as prices continue to drop and new technologies, such as Illumina sequencing, start to be used. PMID- 22065436 TI - Rapid retrieval of DNA target sequences by primer extension capture. AB - There is a widespread need for methods to enrich DNA samples for sequences of interest prior to high-throughput sequencing and to reduce the costs associated with a shotgun approach. While useful for targeting megabase-sized regions in a few samples, hybridization capture approaches such as those using microarrays currently involve bulky handling steps, long incubation times, and high per sample costs. In contrast, the primer extension capture (PEC) method allows direct selection of small genomic regions from DNA sources within 2 h, with low costs for use with parallel samples. PEC promises useful applications in studies such as ancient DNA or forensic sequencing, taxonomic surveying of metagenomic samples, or genomic mapping of repetitive elements. PMID- 22065437 TI - SNP discovery and genotyping for evolutionary genetics using RAD sequencing. AB - Next-generation sequencing technologies are revolutionizing the field of evolutionary biology, opening the possibility for genetic analysis at scales not previously possible. Research in population genetics, quantitative trait mapping, comparative genomics, and phylogeography that was unthinkable even a few years ago is now possible. More importantly, these next-generation sequencing studies can be performed in organisms for which few genomic resources presently exist. To speed this revolution in evolutionary genetics, we have developed Restriction site Associated DNA (RAD) genotyping, a method that uses Illumina next-generation sequencing to simultaneously discover and score tens to hundreds of thousands of single-nucleotide polymorphism (SNP) markers in hundreds of individuals for minimal investment of resources. In this chapter, we describe the core RAD-seq protocol, which can be modified to suit a diversity of evolutionary genetic questions. In addition, we discuss bioinformatic considerations that arise from unique aspects of next-generation sequencing data as compared to traditional marker-based approaches, and we outline some general analytical approaches for RAD-seq and similar data. Despite considerable progress, the development of analytical tools remains in its infancy, and further work is needed to fully quantify sampling variance and biases in these data types. PMID- 22065438 TI - DNA microarray-based mutation discovery and genotyping. AB - DNA microarrays provide an efficient means of identifying single-nucleotide polymorphisms (SNPs) in DNA samples and characterizing their frequencies in individual and mixed samples. We have studied the parameters that determine the sensitivity of DNA probes to SNPs and found that the melting temperature (T (m)) of the probe is the primary determinant of probe sensitivity. An isothermal melting temperature DNA microarray design, in which the T (m) of all probes is tightly distributed, can be implemented by varying the length of DNA probes within a single DNA microarray. I describe guidelines for designing isothermal melting temperature DNA microarrays and protocols for labeling and hybridizing DNA samples to DNA microarrays for SNP discovery, genotyping, and quantitative determination of allele frequencies in mixed samples. PMID- 22065439 TI - Genotyping with Sequenom. AB - Often in evolutionary genetics research, one needs to analyze polymorphisms in populations for which cost-efficient high-throughput arrays are nonexistent, either because the species is not a model organism or because the populations have been subjected to such specific conditions that their base variation is almost unique. In this situation, custom-made genotyping assays are required. Sequenom's MassARRAY((r)) genotyping platform is a powerful and flexible method for assaying up to a few thousand markers and up to thousands of individuals. It is based on distinguishing allele-specific primer extension products by mass spectrometry (MALDI-TOF). Most stages of the experimental protocol reflect adaptations of established PCR protocols to multiplexing, which allows the simultaneous amplification and detection of multiple markers per reaction. PMID- 22065440 TI - Isolating microsatellite loci: looking back, looking ahead. AB - Microsatellite DNA loci are tandemly repeated simple sequence repeats (SSRs) that are ubiquitous in eukaryotic genomes. When flanked by unique sequences, length variation (driven by high rates of strand slippage during DNA replication) at a given repeat locus can be assayed by PCR and electrophoretic separation of the resulting DNA fragments (representing alleles defined by fragment size or repeat number at that locus). In nonmodel organisms that do not have sequence information at SSR loci (or at SSRs in a closely related taxon), microsatellites must be isolated and sequenced de novo. Traditionally, this has been accomplished with cloning of genomic DNA fragments enriched for SSRs, a protocol described in detail here. PCR primers flanking microsatellite repeats can be used to assay repeat length variation among individuals (typically through fluorescent labeling of one strand and capillary electrophoresis), useful for questions related to population variation, individual assignment, mating studies, selection scans, mapping, and phenotypic traits. High-throughput next-generation sequencing will likely supplant traditional cloning methods for the discovery of microsatellite loci. PMID- 22065441 TI - Design of custom oligonucleotide microarrays for single species or interspecies hybrids using Array Oligo Selector. AB - New technologies for DNA sequencing have made it feasible to determine the genome sequence of any organism of interest. This sequence is the resource required to create tools for downstream studies, including DNA microarrays. A number of vendors can produce DNA microarrays containing customer-specified sequences, allowing investigators to design and order arrays customized for any species of interest. Freely available, user-friendly computer programs are available for designing microarray probes. These design programs can be used to create probes that distinguish between two related genomes, allowing investigation of gene expression or gene representation in intra- or interspecies hybrids or in samples containing DNA from multiple species. PMID- 22065442 TI - Identification of homologous gene sequences by PCR with degenerate primers. AB - Degenerate primers are mixtures of similar oligonucleotides that are used in a PCR, so-called degenerate PCR, to amplify unknown DNA sequences, typically coding sequences of genes. Degenerate primers are designed based on sequence data of related and already sequenced gene homologs. This method is useful for identifying new members of a gene family or orthologous genes from different organisms where genomic information is not available. We describe here how to design degenerate primers, set up the PCR (with genomic DNA or cDNA as a template), clone the resulting PCR fragments, and sequence them. Since this method only yields partial coding sequences, complete gene sequences must then be achieved by other approaches such as inverse PCR (see Chapter 16), 5' RACE, 3' RACE, or circular RACE (see Chapter 15). PMID- 22065443 TI - Characterizing cDNA ends by circular RACE. AB - Rapid amplification of cDNA ends (RACE) is a widely used PCR-based method to identify the 5' and 3' ends of cDNA transcripts from partial cDNAs. While conceptually simple, this method often requires substantial optimization before accurate end identification is achieved. This is due in part to the anchoring of a universal primer to a cDNA or mRNA for PCR, which can lead to the generation of nonspecific amplification. Here, we describe an improvement of the original RACE method, circular RACE, which can be used to simultaneously identify both the 5' and 3' end of a target cDNA. PMID- 22065444 TI - Identification of DNA sequences that flank a known region by inverse PCR. AB - The Polymerase Chain Reaction (PCR) with its multiple applications in molecular genetic analysis is the cornerstone of modern basic and applied biomedical research. This chapter focuses on the inverse PCR technique that has been used widely over the last two decades in genotyping and chromosome walking applications for the isolation of unknown DNA sequences upstream and downstream of a known DNA region. The method is based on the use of circularized templates and primers facing outward from the known sequence, rather than primers facing each other used in conventional PCR. As a result, the original genome sequence is rearranged, and stretches of known sequence end up flanking the unknown DNA sequence in the inverse PCR product. I also discuss the special case of using outward facing primers to isolate the intergenic region between genes clustered in tandem or inverted arrangement, since it can hugely simplify the cloning of cis-regulatory sequences in new species of interest. PMID- 22065445 TI - Quantification of transcript levels with quantitative RT-PCR. AB - Differential gene expression is a key factor driving phenotypic divergence. Determining when and where gene expression has diverged between organisms requires a quantitative method. While large-scale approaches such as microarrays or high-throughput mRNA sequencing can identify candidates, quantitative RT-PCR is the definitive method for confirming gene expression differences. Here, we describe the steps for performing qRT-PCR including extracting total RNA, reverse transcribing it to make a pool of cDNA, and then quantifying relative expression of a few candidate genes using real-time or quantitative PCR. PMID- 22065446 TI - Using pyrosequencing to measure allele-specific mRNA abundance and infer the effects of cis- and trans-regulatory differences. AB - Changes in gene expression are an important source of phenotypic differences within and between species. Differences in RNA abundance can be readily quantified between genotypes using a variety of tools, including microarrays, quantitative real-time PCR, cDNA sequencing, and in situ hybridization, but determining the genetic basis of heritable expression differences has historically been less straightforward. Genetic changes that affect RNA abundance can be broadly classified into two groups depending on how they affect gene expression: cis-acting changes affect expression of a single allele in a diploid cell and are typically located close to the affected gene in the genome, whereas trans-acting changes affect expression of both alleles of a gene in a diploid cell and can be located virtually anywhere within a genome. By comparing relative expression of two alleles in an F(1) hybrid with relative expression between the two parental genotypes, the net effects of cis- and trans-acting changes can be discerned. Here, I describe how pyrosequencing can be used to obtain relative gene-specific and allele-specific expression. I also describe how such data can be used to infer the relative contribution of cis- and trans-acting changes to expression differences between genotypes. PMID- 22065447 TI - Whole-mount in situ hybridization of sectioned tissues of species hybrids to detect cis-regulatory changes in gene expression pattern. AB - To distinguish whether differences in gene expression between species or between individuals of the same species are caused by cis-regulatory changes or by distribution differences in trans-regulatory proteins, comparison of species specific mRNA expression in an F1 hybrid by whole-mount in situ hybridization is a rarely used yet very powerful tool. If asymmetric expression pattern is observed for the two alleles, this implies a cis-regulatory divergence of this gene. Alternatively, if symmetric expression pattern is observed for both alleles, the change in expression of this gene is probably caused by changes in the distribution of trans-regulatory proteins. In this chapter, I describe how to prepare RNA probes, tissue samples and how to detect mRNA expression pattern using in situ hybridization. Although I choose to present here the detection of yellow-related gene (YRG) expression pattern in the larval epidermis of swallowtail butterflies, this protocol can be adapted to other species and tissues. YRG mRNA expression is correlated with interspecific differences of yellow and green larval color pattern such as V-shaped markings in swallowtail butterflies. F1 hybrids show an intermediate color pattern between parental species. In this case, both species-specific YRG mRNA showed a similar expression pattern in F1 hybrids, suggesting that the change in expression of YRG is mainly caused by changes in the distribution of trans-regulatory proteins. PMID- 22065448 TI - Identifying fluorescently labeled single molecules in image stacks using machine learning. AB - In the past several years, a host of new technologies have made it possible to visualize single molecules within cells and organisms (Raj et al., Nat Methods 5:877-879, 2008; Pare et al., Curr Biol 19:2037-2042, 2009; Lu and Tsourkas, Nucleic Acids Res 37:e100, 2009; Femino et al., Science 280:585-590, 1998; Rodriguez et al., Semin Cell Dev Biol 18:202-208, 2007; Betzig et al., Science 313:1642-1645, 2006; Rust et al., Nat Methods 3:793-796, 2006; Fusco et al., Curr Biol 13:161-167, 2003). Many of these are based on fluorescence, either fluorescent proteins or fluorescent dyes coupled to a molecule of interest. In many applications, the fluorescent signal is limited to a few pixels, which poses a classic signal processing problem: how can actual signal be distinguished from background noise? In this chapter, I present a MATLAB (MathWorks (2010) MATLAB. Retrieved from http://www.mathworks.com) software suite designed to work with these single-molecule visualization technologies (Rifkin (2010) spotFinding Suite. http://www.biology.ucsd.edu/labs/rifkin/software.html). It takes images or image stacks from a fluorescence microscope as input and outputs locations of the molecules. Although the software was developed for the specific application of identifying single mRNA transcripts in fixed specimens, it is more general than this and can be used and/or customized for other applications that produce localized signals embedded in a potentially noisy background. The analysis pipeline consists of the following steps: (a) create a gold-standard dataset, (b) train a machine-learning algorithm to classify image features as signal or noise depending upon user defined statistics, (c) run the machine-learning algorithm on a new dataset to identify mRNA locations, and (d) visually inspect and correct the results. PMID- 22065449 TI - Experimental approaches to evaluate the contributions of candidate cis-regulatory mutations to phenotypic evolution. AB - Elucidating the molecular bases by which phenotypic traits have evolved provides a glimpse into the past, allowing the characterization of genetic changes that cumulatively contribute to evolutionary innovations. Historically, much of the experimental attention has been focused on changes in protein-coding regions that can readily be identified by the genetic code for translating gene coding sequences into proteins. Resultantly, the role of noncoding sequences in trait evolution has remained more mysterious. In recent years, several studies have reached an unprecedented level of detail in describing how noncoding mutations in gene cis-regulatory elements contribute to morphological evolution. Based on these and other studies, we describe an experimental framework and some of the genetic and molecular methods to connect a particular cis-regulatory mutation to the evolution of any phenotypic trait. PMID- 22065450 TI - Experimental approaches to evaluate the contributions of candidate protein-coding mutations to phenotypic evolution. AB - Identifying mechanisms of molecular adaptation can provide important insights into the process of phenotypic evolution, but it can be exceedingly difficult to quantify the phenotypic effects of specific mutational changes. To verify the adaptive significance of genetically based changes in protein function, it is necessary to document functional differences between the products of derived and wild-type alleles and to demonstrate that such differences impinge on higher level physiological processes (and ultimately, fitness). In the case of metabolic enzymes, this requires documenting in vivo differences in reaction rate that give rise to differences in flux through the pathway in which the enzymes function. These measured differences in pathway flux should then give rise to differences in cellular or systemic physiology that affect fitness-related variation in whole organism performance. Efforts to establish these causal connections between genotype, phenotype, and fitness require experiments that carefully control for environmental variation and background genetic variation. Here, we discuss experimental approaches to evaluate the contributions of amino-acid mutations to adaptive phenotypic change. We discuss conceptual and methodological issues associated with in vitro and in vivo studies of protein function, and the evolutionary insights that can be gleaned from such studies. We also discuss the importance of isolating the effects of individual mutations to distinguish between positively selected substitutions that directly contribute to improvements in protein function versus positively selected, compensatory substitutions that mitigate negative pleiotropic effects of antecedent changes. PMID- 22065451 TI - Making reporter gene constructs to analyze cis-regulatory elements. AB - Cis-regulatory sequences control when, where, and how much genes are transcribed. A better understanding on these elements is a fundamental keystone to better understand development, cell differentiation, and morphogenesis. Several methods based on in silico analysis or ChIP-seq experiments have been developed to detect cis-acting sequences. Here, we describe a protocol to isolate such sequences from genomic DNA and to clone them into expression vectors for functional assays using the Gateway cloning technology. PMID- 22065452 TI - PCR-directed in vivo plasmid construction using homologous recombination in baker's yeast. AB - A variety of applications require the creation of custom-designed plasmids, including transgenic reporters, heterologous gene fusions, and phenotypic rescue plasmids. These plasmids are created traditionally using restriction digests and in vitro ligation reactions, but these techniques are dependent on available restriction sites and can be laborious given the size and number of fragments to be ligated. The baker's yeast Saccharomyces cerevisiae provides a powerful platform to create nearly any plasmid through PCR-directed yeast-mediated ligation. This technique can ligate complex plasmids of up to 50 kilobasepairs (kb) in vivo to produce plasmids with precisely defined sequences. PMID- 22065453 TI - Production of fosmid genomic libraries optimized for liquid culture recombineering and cross-species transgenesis. AB - Genomic DNA libraries are a valuable source of large constructs that can contain all the regulatory elements necessary for recapitulating wild-type gene expression when introduced into animal genomes as a transgene. Such clones can be directly used in complementation studies. In combination with recombineering manipulation, the tagged genomic clones can serve as faithful in vivo gene activity reporters that enable studies of tissue specificity of gene expression, subcellular protein localization, and affinity purification of complexes. We present a detailed protocol for generating an unbiased genomic library in a custom pFlyFos vector that is optimized for liquid culture recombineering manipulation and site-specific transgenesis of fosmid-size loci across different Drosophila species. The cross-species properties of the library can be used, for example, to establish the specificity of RNAi phenotypes or to selectively introgress specific genomic loci among different Drosophila species making it an ideal tool for experimental evolutionary studies. The FlyFos system can be easily adapted to other organisms. PMID- 22065454 TI - Recombination-mediated genetic engineering of large genomic DNA transgenes. AB - Faithful gene activity reporters are a useful tool for evo-devo studies enabling selective introduction of specific loci between species and assaying the activity of large gene regulatory sequences. The use of large genomic constructs such as BACs and fosmids provides an efficient platform for exploration of gene function under endogenous regulatory control. Despite their large size they can be easily engineered using in vivo homologous recombination in Escherichia coli (recombineering). We have previously demonstrated that the efficiency and fidelity of recombineering are sufficient to allow high-throughput transgene engineering in liquid culture, and have successfully applied this approach in several model systems. Here, we present a detailed protocol for recombineering of BAC/fosmid transgenes for expression of fluorescent or affinity tagged proteins in Drosophila under endogenous in vivo regulatory control. The tag coding sequence is seamlessly recombineered into the genomic region contained in the BAC/fosmid clone, which is then integrated into the fly genome using phiC31 recombination. This protocol can be easily adapted to other recombineering projects. PMID- 22065455 TI - Overlap extension PCR: an efficient method for transgene construction. AB - Combining genes or regulatory elements to make hybrid genes is a widely used methodology throughout the biological sciences. Here, we describe an optimized approach for hybrid gene construction called overlap extension PCR. In this method, the polymerase chain reaction (PCR) is employed for efficient and reliable construction of hybrid genes. A PCR-based approach does not rely on available restriction sites or other specific sequences, an advantage over more conventional cloning or recombineering methods. With the use of high-fidelity DNA polymerase, this method can be used for making even very large constructs (>20 kb) with minimal unwanted mutations. Finally, overlap extension-PCR can be used as a means for site-directed mutagenesis, introducing desired mutations to the final hybrid gene. PMID- 22065456 TI - Gene knockdown analysis by double-stranded RNA injection. AB - The discovery of RNAi, in which double-stranded RNA (dsRNA) suppresses the translation of homologous mRNA, has had a huge impact on evolutionary genetics by enabling the analysis of loss-of-function phenotypes in organisms in which classical genetic analysis is laborious or impossible. In this chapter, we discuss an RNAi method via simple dsRNA injection in the red flour beetle, Tribolium castaneum. Tribolium is gaining popularity in evolutionary genetics due in part to the ease of RNAi application. We describe procedures for dsRNA synthesis and injection and provide a description of the injection apparatus. In addition, we detail two methods to validate the efficacy of RNAi (real-time PCR and western blot analyses). Although this chapter focuses mainly on Tribolium, many of the molecular biology and injection procedures described here are applicable to other organisms with some modifications. A few notes regarding dsRNA injection in other species are also included. PMID- 22065457 TI - Copper(II)-catalyzed hydrosilylation of ketones using chiral dipyridylphosphane ligands: highly enantioselective synthesis of valuable alcohols. AB - In the presence of PhSiH(3) as the reductant, the combination of enantiomeric dipyridylphosphane ligands and Cu(OAc)(2).H(2)O, which is an easy-to-handle and inexpensive copper salt, led to a remarkably practical and versatile chiral catalyst system. The stereoselective formation of a selection of synthetically interesting beta-, gamma- or delta-halo alcohols bearing high degrees of enantiopurity (up to 99.9% enantiomeric excess (ee)) was realized with a substrate-to-ligand molar ratio (S/L) of up to 10,000. The present protocol also allowed the hydrosilylation of a diverse spectrum of alkyl aryl ketones with excellent enantioselectivities (up to 98% ee) and exceedingly high turn-over rates (up to 50,000 S/L molar ratio in 50 min reaction time) in air, under very mild conditions, which offers great opportunities for the preparation of various physiologically active targets. The synthetic utility of the chiral products obtained was highlighted by the efficient conversion of optically enriched beta halo alcohols into the corresponding styrene oxide, beta-amino alcohol, and beta azido alcohol, respectively. PMID- 22065458 TI - 4-Amino-2-chloro-benzoic acid. AB - The title compound, C(7)H(6)ClNO(2), crystallizes with two roughly planar mol ecules in the asymmetric unit (r.m.s. deviations = 0.073 and 0.074 A). The amine H atoms of the two mol-ecules have opposite orientations. In the crystal, mol ecules are linked into dimers by pairs of O-H?O hydrogen bonds, generating R(2) (2)(8) loops. N-H?N and N-H?Cl hydrogen bonds link the dimers into a three dimensional network. The crystal studied was found to be a racemic twin. PMID- 22065459 TI - Vascular Ehlers-Danlos syndrome presenting as rapidly progressive multiple arterial aneurysms and dissections. AB - Life expectancy in vascular Ehlers-Danlos syndrome (EDS) is shortened due to spontaneous rupture of arteries, the colon and the gravid uterus. Two adolescent males with vascular EDS illustrate rapid progression of arterial aneurysms, dissections, and rupture. Radiologic imaging played an important role in initially diagnosing and monitoring the evolution of arterial involvement. Both prophylactic and emergency management remain largely ineffective in this connective tissue disorder; however, noninvasive imaging may provide important prognostic information. PMID- 22065460 TI - Transition from anodic titania nanotubes to nanowires: arising from nanotube growth to application in dye-sensitized solar cells. AB - Anodic formation of titania nanowires has been interpreted using a bamboo splitting model; however, a number of phenomena are difficult to explain with this model. Herein, transition from nanotubes to nanowires is investigated by varying the anodizing conditions. The results indicate that the transition requires a large number of hydrogen ions to reduce the passivated area of tube walls, and therefore can be observed only in an intermediate chemical dissolution environment. Accordingly, a model in terms of stretching and splitting is proposed to interpret the transition process. The model provides a basis to suppress the nanowires with surface treatments before anodization and to clear the nanowires with an ultrasonication process after anodization. The nanotube nanowire transition also arises when the tubes are directly used in dye sensitized solar cells. Treatment with titanium tetrachloride solution for about 10 h is found to be effective in suppressing the nanowires, and thus improving the photovoltaic properties of the solar cells. PMID- 22065461 TI - 5-Methyl-1,2-oxazole-3-carb-oxy-lic acid. AB - In the crystal structure of the title compound, C(5)H(5)NO(3), all the non-H atoms are approximately coplanar: the carb-oxy O atoms deviating by 0.013 (2) and -0.075 (2) A from the isoxazole ring plane. In the crystal, the molecules form inversion dimers linked by pairs of O-H?O hydrogen bonds and the dimers stack via pi-pi inter-actions [centroid-centroid distance = 3.234 (2) A]. PMID- 22065462 TI - {N'-[1-(2-Pyrid-yl)ethyl-idene-kappaN]benzo-hydrazidato-kappaN',O}{N'-[1-(2-pyrid yl)ethyl-idene-kappaN]benzohydrazide-kappaN',O}copper(II) trichloro-acetate. AB - In the title complex, [Cu(C(14)H(13)N(3)O)(C(14)H(12)N(3)O)](CCl(3)COO), the central Cu(II) ion exhibits a distorted octa-hedral geometry with the two ligands coordinating in an meridional format. The N(4)O(2) ligand environment is defined by two benzoyl O atoms, two pyridyl N atoms and imino N atoms. As evidenced by the bond lengths, the two benzohydrazone ligands exist in distinctively different forms, one of them as a regular neutral ligand and the other as an anionic enolate arising from deprotonation. The much longer Cu-O bond and longer Cu-N bond lengths in the neutral benzohydrazone ligand imply weak ligation in comparison with the anionic enolate form. The acute angles of the five-membered rings cause a significant deviation from a regular octa-hedral geometry. PMID- 22065463 TI - Synthesis and analytical investigation of C-terminally modified peptide aldehydes and ketone: application to oxime ligation. AB - C-terminally modified peptides aldehyde (glycinal and alpha-oxo aldehyde peptides) and ketone (pyruvic acid-containing peptide) were synthesised to get new insights into the mechanism of acido-catalysed oxime ligation. Their tetrahedral hydrated forms were investigated in solution and in the gas phase, using NMR and in-source collision-induced dissociation mass spectrometry, respectively, and the kinetics of the oximation reactions followed using analytical HPLC. The results obtained confirmed that the first step of the oximation reaction was the limiting step for the pyruvic acid-containing peptides because of the steric effect and of the carbon angular strain of the ketone. The second step is the determining step for the aldehyde peptides because the basicity of the oxygen of the hydroxyl function of the tetrahedral form is greater for glycinal than for alpha-oxo aldehyde. These data strongly suggest that the hydrated form of the aldehyde partner has to be considered when oxime reactions are performed in aqueous buffer. PMID- 22065464 TI - Insomnia as predictor versus outcome of PTSD and depression among Iraq combat veterans. AB - OBJECTIVES: The study conducted a longitudinal assessment of insomnia as an antecedent versus consequence of posttraumatic stress disorder (PTSD) and depression symptoms among combat veterans. DESIGN: Two postdeployment time points were used in combination with structural equation modeling to examine the relative strength of two possible directions of prediction: insomnia as a predictor of psychological symptoms, and psychological symptoms as a predictor of insomnia. Participants were active duty soldiers (N = 659) in a brigade combat team who were assessed 4 months after their return from a 12-month deployment to Iraq, and then again eight months later. RESULTS: Although both insomnia and psychological symptoms were associated at both time periods and across time periods, insomnia at 4 months postdeployment was a significant predictor of change in depression and PTSD symptoms at 12 months postdeployment, whereas depression and PTSD symptoms at 4 months postdeployment were not significant predictors of change in insomnia at 12 months postdeployment. CONCLUSIONS: Results support the role of insomnia in the development of additional psychological problems and highlight the clinical implications for combat veterans, to include the importance of longitudinal assessment and monitoring of sleep disturbances, and the need for early intervention. PMID- 22065465 TI - 4-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)benzonitrile. AB - In the title compound, C(13)H(7)ClN(4), the imidazopyridazine ring system is essentially planar [maximum deviation 0.015 (1) A]. It is inclined to the benzene ring of the benzonitrile group by 11.31 (2) degrees . In the crystal, molecules are linked via C-H?Cl and C-H?N interactions. PMID- 22065466 TI - Bis{2-[(E)-(5-tert-butyl-2-hy-droxy-phen-yl)diazen-yl]benzoato}dimethyl-tin(IV). AB - In the title diorganotin dicarboxyl-ate, [Sn(CH(3))(2)(C(17)H(17)N(2)O(3))(2)], the tin(IV) atom is six-coordinated by four O atoms derived from asymmetrically coordinating carboxyl-ate ligands, and two methyl-C atoms. The resulting C(2)O(4) donor set defines a skew-trapezoidal bipyramid with the Sn-C bonds disposed over the weaker Sn-O bonds. Within each carboxyl-ate ligand, the hydroxyl-H atom forms bifurcated O-H?(O,N) hydrogen bonds with carboxyl-ate-O and azo-N atoms. The dihedral angles between the benzene rings in the two ligands are 10.44 (11) and 34.24 (11) degrees . In the crystal, centrosymmetric dimers are formed through pairs of Sn?O inter-actions [2.8802 (16) A], and the dimers are linked into supra molecular layers in the ac plane by C-H?pi inter-actions. PMID- 22065467 TI - rac-(6S)-6-Hy-droxy-6-{2-[2-(propan-2-yl-idene)hydrazinyl-idene]prop yl}indolo[2,1-b]quinazolin-12(6H)-one. AB - The chiral title compound, C(21)H(20)N(4)O(2), crystallizes as a racemic mixture. In the crystal, mol-ecules form centrosymmetric pi-overlapping dimers [inter planar distance = 3.338 (6) A], which are further connected along the a axis forming centrosymmetric dimers via O-H?N hydrogen bonds. C-H?O inter-actions are also observed. The indolo[2,1-b]quinazoline group is somewhat bent, with a small dihedral angle of 6.3 (4) degrees between the plane of the quinazoline system and the plane of the benzene ring of the indole moiety. The C=N-N=C atoms of the azine group is oriented almost perpendicular [84.1 (2) degrees ] to the mean plane of the quinazoline system. PMID- 22065468 TI - Assessment of community food resources: A Latino neighborhood study in upstate New York. AB - This study aims to assess availability, affordability, and accessibility of food items in a low-income Latino neighborhood within a small city using an on-site food store survey. Store locations were identified by on-site GPS. Results showed the Latino neighborhood had limited availability and above average cost of high fiber bread. Fresh vegetables were more expensive compared to the non-Latino neighborhood, and more stores in the Latino neighborhood participated in Supplemental Nutrition Assistance Food Program. The lack of supermarkets, fewer stores with disability access, and the lack of public transportation left Latino residents without a vehicle or with physical disabilities with few food shopping options. PMID- 22065469 TI - (2-{[2-(1H-Benzimidazol-2-yl-kappaN)phen-yl]imino-methyl-kappaN}-5-methyl phenolato-kappaO)chloridozinc(II). AB - In the title mononuclear complex, [Zn(C(21)H(16)N(3)O)Cl], the Zn(II) ion is coordinated in a distorted tetra-hedral geometry by two benzimidazole N atoms and one phenolate O atom from the tridentate Schiff base ligand and a chloride ligand. The benzimidazole ring system forms dihedral angles of 26.68 (9) and 56.16 (9) degrees with the adjacent benzene ring and the methyl-phenolate group benzene ring, respectively. In the crystal, mol-ecules are linked by N-H?Cl hydrogen bonds into chains along [100]. Furthermore, weak C-H?O and C-H?pi inter actions, in addition to pi-pi inter-actions with centroid-centroid distances in the range 3.5826 (13)-3.9681 (13) A, are also observed. PMID- 22065470 TI - Diaqua-(5-carb-oxy-benzene-1,3-dicarboxyl-ato-kappaO,O)(6,6'-dimethyl-2,2' bipyridine-kappaN,N')nickel(II) hepta-hydrate. AB - In the title compound, [Ni(C(9)H(4)O(6))(C(12)H(12)N(2))(H(2)O)(2)].7H(2)O, the Ni(II) atom is six-coordinated by two O atoms from a chelating carboxyl-ate group of a 5-carb-oxy-benzene-1,3-dicarboxyl-ate ligand, two O atoms of two water mol ecules and two N atoms from a 6,6'-dimethyl-2,2'-bipyridine ligand in a distorted octa-hedral geometry. The compound exhibits a three-dimensional supra-molecular structure composed of the complex mol-ecules and lattice water mol-ecules, which are linked together by inter-molecular O-H?O hydrogen bonds and partly overlapping pi-pi inter-actions between the pyridine and benzene rings [centroid centroid distances = 3.922 (2) and 3.921 (2) A]. One of the lattice water mol ecules is disordered over two positions in an occupancy ratio of 0.521 (6):0.479 (6). PMID- 22065471 TI - Bis[MU-N'-(2-methyl-1-oxidopropanyl-idene)-2-oxidobenzohydrazidato]tetra-pyridine trinickel(II). AB - The asymmetric unit of the title trinuclear Ni(II) compound, [Ni(3)(C(11)H(11)N(2)O(3))(C(5)H(5)N)(4)], contains two independent mol-ecules which are located on individual inversion centres. The central Ni atom, located on an inversion centre, is coordinated by two pyridine N atoms and is further N,O chelated by two N-(2-methyl-propano-yl)salicyloylhydrazidate anions in an elongated octa-hedral coordination geometry. The terminal Ni atom is coordinated by a pyridine ligand and is further N,N',O-chelated by an N-(2-methyl-propano yl)salicyloyl-hydrazidate anion in a distorted square-planar coordination geometry. Weak intra-molecular C-H?O hydrogen bonding is observed in the structure. PMID- 22065472 TI - Moyamoya disease (presenting as schizophrenia). AB - The aetiology of Schizophrenia is still obscure. This case report is of interest because it draws attention to a hitherto neglected area in this filed, i.e., the role of cerebro-vascular malformation and the resulting insufficiency in the cerebral circulation as a possible factor in the pathogenesis of Schizophrenia. PMID- 22065473 TI - Medical students' attitudes toward the anatomy dissection room in relation to personality. AB - Assessment of the personalities of medical students could enable medical educators to formulate strategies for the best development of academic and clinical competencies. In this article, we focus on the experience of students in the anatomy dissecting room. While there have been many attempts to evaluate the emotional responses of medical students to human cadaveric dissection, there has been no investigation into how different personality traits affect the responses. The main hypothesis tested was that there is a relationship between personality traits and attitudes toward the dissection room. For the present study, a group of French medical students (n = 403; mean age 21.3 +/- 1.6; 65.3% female) completed a "Big Five" personality inventory and a questionnaire to assess their attitudes in regard to human dissection. The findings are consistent with our hypothesis, in that we found a relationship between reporting anxiety and four of the "Big Five" dimensions (all except openness). The rated level of anxiety was positively correlated with negative affectivity, more strongly at the beginning than at the end of the course. There were significant gender differences in attitudes toward dissection. The findings are discussed in relation to the possibility of preparing students for the dissecting room experience and also in relation to the students' understanding of mortality issues. PMID- 22065474 TI - Browsing software of the Visible Korean data used for teaching sectional anatomy. AB - The interpretation of computed tomographs (CTs) and magnetic resonance images (MRIs) to diagnose clinical conditions requires basic knowledge of sectional anatomy. Sectional anatomy has traditionally been taught using sectioned cadavers, atlases, and/or computer software. The computer software commonly used for this subject is practical and efficient for students but could be more advanced. The objective of this research was to present browsing software developed from the Visible Korean images that can be used for teaching sectional anatomy. One thousand seven hundred and two sets of MRIs, CTs, and sectioned images (intervals, one millimeter) of a whole male cadaver were prepared. Over 900 structures in the sectioned images were outlined and then filled with different colors to elaborate each structure. Software was developed where four corresponding images could be displayed simultaneously; in addition, the structures in the image data could be readily recognized with the aid of the color-filled outlines. The software, distributed free of charge, could be a valuable tool to teach medical students. For example, sectional anatomy could be taught by showing the sectioned images with real color and high resolution. Students could then review the lecture by using the sectioned and color-filled images on their own computers. Students could also be evaluated using the same software. Furthermore, other investigators would be able to replace the images for more comprehensive sectional anatomy. PMID- 22065477 TI - Synthesis and helical structure of spiroborate-based double-stranded helicate with oligophenol strands bearing bipyridine units. PMID- 22065478 TI - Computational study of bond dissociation enthalpies for substituted beta-O-4 lignin model compounds. AB - The biopolymer lignin is a potential source of valuable chemicals. Phenethyl phenyl ether (PPE) is representative of the dominant beta-O-4 ether linkage. DFT is used to calculate the Boltzmann-weighted carbon-oxygen and carbon-carbon bond dissociation enthalpies (BDEs) of substituted PPE. These values are important for understanding lignin decomposition. Exclusion of all conformers that have distributions of less than 5% at 298 K impacts the BDE by less than 1 kcal mol( 1). We find that aliphatic hydroxyl/methylhydroxyl substituents introduce only small changes to the BDEs (0-3 kcal mol(-1)). Substitution on the phenyl ring at the ortho position substantially lowers the C-O BDE, except in combination with the hydroxyl/methylhydroxyl substituents, for which the effect of methoxy substitution is reduced by hydrogen bonding. Hydrogen bonding between the aliphatic substituents and the ether oxygen in the PPE derivatives has a significant influence on the BDE. CCSD(T)-calculated BDEs and hydrogen-bond strengths of ortho-substituted anisoles, when compared with M06-2X values, confirm that the latter method is sufficient to describe the molecules studied and provide an important benchmark for lignin model compounds. PMID- 22065479 TI - Influence of uncommon histology on breast conservation therapy for breast cancer biology dictates technique? AB - INTRODUCTION: Although trends and variations in the use of breast conservation therapy (BCT) for ductal carcinoma have been studied, little is known about uncommon breast cancer histologies. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to identify 338,682 patients with T1 or T2 (<=5 cm) ductal, lobular, tubular, mucinous, medullary, or papillary carcinoma of the breast from 1998 to 2008. Multivariate logistic regression analysis was used to identify predictors of BCT. RESULTS: The majority of patients underwent BCT (60%). The rate of BCT remained relatively constant from 1998 to 2008 overall but varied from 50% for lobular to 79% for tubular. The highest rate of mastectomy was seen in lobular (49%). Nodal positivity following surgical staging was lowest for tubular (6%) and mucinous (8%). Adjuvant radiation was given to 72% overall and was lowest for papillary (58%). Predictors of BCT included tubular (OR 1.8, 95% CI 1.7-1.9) and medullary (OR 2.0, 95% CI 1.8-2.2) subtypes (vs. ductal). CONCLUSIONS: Patients with uncommon breast cancer histologies show wide variation in the application of BCT depending on the primary tumor. This suggests that an individualized approach in the use of BCT depending on histology should be used. PMID- 22065480 TI - 5-Hy-droxy-3-methyl-5-phenyl-4,5-di-hydro-1H-pyrazole-1-carbothio-amide. AB - In the title compound C(11)H(13)N(3)OS, the aromatic ring and the dihydro pyrazole ring are oriented orthogonally with respect to each other, making a dihedral angle of 89.92 (9) degrees . An intra-molecular O-H?S hydrogen bond occurs. In the crystal, weak N-H?N and N-H?S hydrogen bonds link the mol-ecules into a columnar stack propagating along the b axis. PMID- 22065481 TI - Minimal genotype--phenotype correlation for small deletions within distal 1p36. PMID- 22065482 TI - Flocculation and transcriptional adaptation to fermentation conditions in a recombinant wine yeast strain defective for KNR4/SMI1. AB - KNR4 defective recombinant wine yeast strains were previously shown to oversecrete mannoproteins during alcoholic fermentation and, depending on the genetic background, to contribute to protein stability of white wines. We have tried to get a deeper insight into the consequences of KNR4 deletion in a wine yeast strain, from both a biological and an enological standpoint, and to understand the mechanisms leading to improved mannoprotein release. In fermentation experiments, followed by aging on lees, and compared to the parent strain, the recombinant strain shows increased release of mannoproteins during the fermentation but little increase during aging. Mannoprotein release by the recombinant strain takes place mainly during the fermentation step. In contrast, autolysis of the recombinant strain keeps going after aging for 78 days. In addition, the recombinant strain is moderately flocculent, which would be interesting for the production of sparkling wines. This might be related to changes in the expression of Flo1p-regulated genes. The new biological processes affected by KNR4 deletion in wine yeasts, as revealed by this transcriptomic study are flocculation, adaptation to anaerobiosis, oxidative stress response, and ethanol tolerance, as well as FKS1 overexpression; but no overexpression was detected for genes coding for major structural mannoproteins of the cell wall. PMID- 22065483 TI - Carboxylate-directed tandem functionalisations of alpha,beta-dihaloalkenoic acids with 1-alkynes: a straightforward access to (Z)-configured, alpha,beta substituted gamma-alkylidenebutenolides. PMID- 22065484 TI - 2,4-Diamino-5-(4-chloro-phen-yl)-6-ethyl-pyrimidin-1-ium 2-acet-amido-benzoate. AB - The title compound, C(12)H(14)ClN(4) (+).C(9)H(8)NO(3) (-), is a salt with a 1:1 ratio of cation and anion components inter-acting with each other forming an R(2) (2)(8) ring motif. The crystal structure is stabilized by hydrogen bonds (N-H?O) involving two different eight-membered rings. One of them is formed between the pyrimidine ring (donor) and the carboxylate group (acceptor) from the benzoate, whereas the other ring is formed by N-H?O interactions, which help to form a dimer between two symmetry-related salts in the unit cell. In addition, an intramolecular C-H?N and intermolecular C-H?Cl interactions help to control the molecules in the unit-cell packing. PMID- 22065485 TI - 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. PMID- 22065486 TI - Peri-operative chemotherapy for resectable colorectal liver metastasis: does timing of systemic therapy matter? AB - BACKGROUND: The benefit of pre-operative chemotherapy in patients with resectable colorectal liver metastases (CRLM) remains ill defined. We sought to evaluate the impact of peri-operative systemic chemotherapy timing on outcome following resection of CRLM. METHODS: 676 patients who underwent surgery for CRLM were identified from two hepatobiliary center databases. Data were collected and analyzed utilizing multivariate, matched, and propensity-score analyses. RESULTS: Median number of metastases was 2 and median tumor size was 3.3 cm. 334 patients (49.4%) received pre-operative chemotherapy while 342(50.6%) did not. Surgical treatment was resection only (n = 555; 82.1%; minor hepatectomy, n = 399; 59.1%). While there was no difference in morbidity following minor liver resection (pre operative chemotherapy: 17.9% versus no pre-operative chemotherapy: 16.5%; P = 0.72), morbidity was higher after major hepatic resection (pre-operative chemotherapy: 23.1% versus no pre-operative chemotherapy: 14.2%; P = 0.06). Patients treated with pre-operative chemotherapy had worse 5-year survival (43%) as compared to patients not treated with pre-operative chemotherapy (55%)(P = 0.009). Controlling for baseline characteristics, pre-operative chemotherapy was not associated with outcome on multivariate (HR = 1.04, P = 0.87) or propensity score analysis (HR = 1.40, P = 0.12). CONCLUSION: Pre-operative chemotherapy was associated with a trend toward increased morbidity among patients undergoing a major hepatic resection. Receipt of pre-operative chemotherapy was associated with neither an advantage nor disadvantage in terms of long-term survival. PMID- 22065487 TI - Intragenic deletion of UBE3A gene in 2 sisters with Angelman syndrome detected by MLPA. PMID- 22065488 TI - High-throughput analysis of intraclonal variability of glycoprotein sialylation. AB - Development of recombinant Chinese Hamster Ovary (CHO) cells producing therapeutic proteins requires analyzing the quality, such as sialic acid content, of proteins produced by many cell clones. In order to perform these analyses, high-throughput methods are required. Conventional methods for quantifying sialic acid, however, require protein purification, which is time consuming and cannot be used for high-throughput analysis. Here we used a high-throughput method (HTM) that we recently developed to analyze the intraclonal variability of 24 CHO cell subclones. The sialic acid content varied significantly from 1 to 70 mg sialic acid/g protein, and the concentration of total proteins secreted by the cells varied from 41 to 214 mg/L. In addition, the sialic acid content was negatively correlated with total protein concentration. This trend agrees with previous theoretical and experimental studies. Overall, the HTM can finish these analyses in 15 minutes, while conventional methods used in previous studies will require at least 24 days. Thus, the HTM can significantly accelerate the analyses of clonal and intraclonal variability in cell line development PMID- 22065489 TI - Synthesis of alpha,beta-unsaturated ketones by Pd-catalyzed decarboxylative allylation of alpha-oxocarboxylates. PMID- 22065490 TI - Temporal decision making in simultaneous timing. AB - With two experiments it was examined whether one or two clocks operate the timing of two intervals presented simultaneously. The target interval always preceded the distracter interval, and was longer than it. Thus, the distracter was completely embedded within the target interval. The participants used the method of temporal production. The stimuli to be judged differed in modality which allowed for testing the hypothesis of modality-specific internal clocks that operate in parallel and independent from one another when two stimuli were presented at the same time. The main results of this study were as follows. First, production times of the target interval increased proportionally with production times of the distracter interval. Second, the auditory distracter interval was on average produced in less time than the visual distracter interval. Third, a target interval that was accompanied by an auditory distracter interval was on average produced in less time than a target interval that was accompanied by a visual distracter interval. The results obtained support the hypothesis of multiple clocks being involved in the timing of different intervals presented simultaneously. PMID- 22065491 TI - Soil amendments with Brassica cover crops for management of Phytophthora blight on squash. AB - BACKGROUND: Phytophthora blight induced by Phytophthora capsici is responsible for serious yield loss in vegetable production in the United States and other countries. This study was conducted to evaluate the efficacy of Brassica cover crops used as soil amendments for managing Phytophthora blight of squash. RESULTS: In greenhouse studies, disease incidence on squash plants was significantly reduced by soil amendment with mustard shoots or roots used at 1 and 2.5% (plant tissue/soil, w/w). The shoots of canola used at 1 or 2.5% also suppressed disease, while the roots of canola or other crops did not reduce disease significantly. In field studies, soil amendments with mustard and canola provided the greatest disease reduction and increased squash yield significantly compared with the non-treated control. Mustard and canola did not appear to be susceptible to P. capsici. CONCLUSION: The results indicated that some Brassica crops, particularly mustard and canola, had the potential to significantly reduce Phytophthora blight on squash when used as soil amendments. As P. capsici has a remarkable ability to develop resistance to chemical fungicides, use of effective Brassica cover crops could be a biorational alternative to fungicides and a valuable component in developing integrated disease management programs. PMID- 22065492 TI - Overexpression of survivin is correlated with increased invasion and metastasis of colorectal cancer. AB - BACKGROUND: The aim of this study was to investigate the association of survivin expression with metastasis of colorectal cancer (CRC). METHODS: RT-PCR and Western blot assays were performed to detect survivin expression in CRC cells and normal intestinal epithelial cell. The expression of survivin gene was also detected in 15 CRC tissues, surrounding and adjacent colon tissues. Moreover, survivin expression in 48 CRC tissues with or without lymph node metastasis was analyzed. Multivariate analysis for lymph node metastasis was performed using logistic regression model. RNA interference was used to inhibit survivin expression in CRC cells and analyze its effect on invasion and metastasis of CRC cells. RESULTS: The expression levels of survivin mRNA and protein were higher in CRC cells than in normal intestinal epithelial cell line. The average levels of survivin mRNA and protein were higher in CRC tissues than surrounding or adjacent colon tissues (P < 0.05). High survivin expression was an independent factor for predicting lymph node metastasis of CRC (P = 0.043). RNAi-mediated survivin knockdown could significantly inhibit in vitro invasion and in vivo metastasis of CRC cells, which might be inactivation of matrix metalloproteinases. CONCLUSION: Targeting survivin will be a potential strategy to suppress metastasis of CRC. PMID- 22065493 TI - A hydrogen-bridged adduct 3,4,6,7,8,9-hexa-hydro-2H-pyrimido[1,2-a]pyrimidin-1 ium [1,3-bis-(tert-butyl-dimethyl-sil-yloxy)-1,3-bis-(pyridin-2-yl)propan-2-yl idene]nitro-nate acetonitrile monosolvate. AB - The title compound, C(7)H(14)N(3) (+).C(25)H(40)N(3)O(4)Si(2) (-).CH(3)CN, was obtained by the reaction of 2-nitro-1,3-di(pyridin-2-yl)-1,3-di(tert-butyl dimethyl-sil-yloxy)propane with 1,3,4,6,7,8-hexa-hydro-2H-pyrimido[1,2 a]pyrimidine. Two hydrogen bonds stabilize the Lewis acid/base pair of the nitro nate and the guanidinium moiety with N?O distances of 2.772 (3) and 2.732 (3) A. Both hydrogen atoms are more closely bound to the guanidinium [N-H distances of 0.83 (3) and 0.93 (3) A] than to the nitro-nate moiety. The nitro-nate is double bonded to the respective carbon with an N=C bond length of 1.316 (3) A. PMID- 22065494 TI - 2,3-Dichloro-pyridine. AB - The complete mol-ecule of the title compound, C(5)H(3)Cl(2)N, is generated by crystallographic twofold symmetry, which forces the pyridine N atom and the opposite C-H group to be statistically disordered. In the crystal, weak aromatic pi-pi stacking [centroid-centroid separation = 3.805 (4) A and slippage = 1.704 A] leads to [100] stacks of mol-ecules. Short Cl?Cl contacts [3.334 (3) A] are also observed. PMID- 22065495 TI - 10,21-Dimethyl-2,7,13,18-tetraphenyl-3,6,14,17 tetraazatricyclo[17.3.1.1]tetracosa-1(23),2,6,8(24),9,11,13,17,19,21-decaene 23,24-diol cyclohexane 0.33-solvate. AB - The title compound, C(46)H(40)N(4)O(2).0.33C(6)H(12), was obtained unintentionally as a product of an attempted synthesis of a cadmium(II) complex of the [2,6-{PhSe(CH(2))(2)N=CPh}(2)C(6)H(2)(4-Me)(OH)] ligand. The full tetra imino-diphenol macrocyclic ligand is generated by the application of an inversion centre. The macrocyclic ligand features strong intra-molecular O-H?N hydrogen bonds. The dihedral angles formed between the phenyl ring incorporated within the macrocycle and the peripheral phenyl rings are 82.99 (8) and 88.20 (8) degrees . The cyclo-hexane solvent mol-ecule lies about a site of [Formula: see text] symmetry. Other solvent within the lattice was disordered and was treated with the SQUEEZE routine [Spek (2009). Acta Cryst. D65, 148-155]. PMID- 22065496 TI - (4-Chloro-3-nitro-benzoato)triphenyl-tin(IV). AB - In the title compound, [Sn(C(6)H(5))(3)(C(7)H(3)ClNO(4))], the four-coordinate Sn(IV) atom exists in a distorted tetra-hedral geometry, formed by a monodentate carboxyl-ate group and three phenyl rings. The conformation is stabilized by an intra-molecular C-H?O hydrogen bond, which generates an S(5) ring. The aromatic ring of the 4-chloro-3-nitro-benzoate ligand makes dihedral angles of 75.64 (12), 64.37 (12) and 2.97 (12) degrees with the three phenyl ligands. The O atoms of the nitro group are disordered over two sets of sites in a 0.817 (5):0.183 (5) ratio. In the crystal, mol-ecules are linked via inter-molecular C-H?O hydrogen bonds into chains running parallel to [010]. PMID- 22065497 TI - A novel model for DNA sequence similarity analysis based on graph theory. AB - Determination of sequence similarity is one of the major steps in computational phylogenetic studies. As we know, during evolutionary history, not only DNA mutations for individual nucleotide but also subsequent rearrangements occurred. It has been one of major tasks of computational biologists to develop novel mathematical descriptors for similarity analysis such that various mutation phenomena information would be involved simultaneously. In this paper, different from traditional methods (eg, nucleotide frequency, geometric representations) as bases for construction of mathematical descriptors, we construct novel mathematical descriptors based on graph theory. In particular, for each DNA sequence, we will set up a weighted directed graph. The adjacency matrix of the directed graph will be used to induce a representative vector for DNA sequence. This new approach measures similarity based on both ordering and frequency of nucleotides so that much more information is involved. As an application, the method is tested on a set of 0.9-kb mtDNA sequences of twelve different primate species. All output phylogenetic trees with various distance estimations have the same topology, and are generally consistent with the reported results from early studies, which proves the new method's efficiency; we also test the new method on a simulated data set, which shows our new method performs better than traditional global alignment method when subsequent rearrangements happen frequently during evolutionary history. PMID- 22065498 TI - A comparison of melancholic and nonmelancholic recurrent major depression in Han Chinese women. AB - BACKGROUND: Although the diagnosis of melancholia has had a long history, the validity of the current DSM-IV definition remains contentious. We report here the first detailed comparison of melancholic and nonmelancholic major depression (MD) in a Chinese population examining in particular whether these two forms of MD differ quantitatively or qualitatively. METHODS: DSM-IV criteria for melancholia were applied to 1,970 Han Chinese women with recurrent MD recruited from 53 provincial mental health centers and psychiatric departments of general medical hospitals in 41 cities. Statistical analyses, utilizing Student's t-tests and Pearson's chi(2) , were calculated using SPSS 13.0. RESULTS: Melancholic patients with MD were distinguished from nonmelancholic by being older, having a later age at onset, more episodes of illness and meeting more A criteria. They also had higher levels of neuroticism and rates of lifetime generalized anxiety disorder, panic disorder, and social and agoraphobia. They had significantly lower rates of childhood sexual abuse but did not differ on other stressful life events or rates of MD in their families. DISCUSSION: Consistent with most prior findings in European and US populations, we find that melancholia is a more clinically severe syndrome than nonmelancholic depression with higher rates of comorbidity. The evidence that it is a more "biological" or qualitatively distinct syndrome, however, is mixed. PMID- 22065499 TI - 1-(tert-But-oxy-carbon-yl)piperidine-4-carb-oxy-lic acid. AB - In the title compound, C(11)H(19)NO(4), the piperidine ring adopts a chair conformation. In the crystal, mol-ecules are linked by inter-molecular O-H?O and C-H?O hydrogen bonds, forming a layer parallel to the bc plane. PMID- 22065500 TI - Methyl 2,2-bis-(2,4-dinitro-phen-yl)ethano-ate. AB - In the title compound, C(15)H(10)N(4)O(10), the dihedral angle between the aromatic rings is 89.05 (16) degrees . One O atom of one of the nitro groups is disordered over two sites in a 0.70:0.30 ratio. In the crystal, the mol-ecules are linked by weak C-H?O inter-actions. PMID- 22065501 TI - Bis[1,3-bis(1-propyl-1H-benzimidazol-2-yl)-2-oxapropane]-cadmium(II) dipicrate dimethyl-formamide monosolvate. AB - In the title compound, [Cd(C(22)H(26)N(4)O)(2)](C(6)H(2)N(3)O(7))(2).C(3)H(7)NO, the Cd(II) ion is coordinated by four N atoms and two O atoms from two tridentate 1,3-bis-(1-propyl-1H-benzimidazol-2-yl)-2-oxopropane ligands in a distorted octa hedral coordination environment. There are significant differences in the chemically equivalent Cd-O bond lengths [2.618 (2) A and 2.561 (2) A]. PMID- 22065502 TI - Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A. AB - Classical Hutchinson-Gilford progeria syndrome (HGPS) is caused by LMNA mutations that generate an alternatively spliced form of lamin A, termed progerin. HGPS patients present in early childhood with atherosclerosis and striking features of accelerated aging. We report on two pedigrees of adult-onset coronary artery disease with progeroid features, who were referred to our International Registry of Werner Syndrome (WS) because of clinical features consistent with the diagnosis. No mutations were identified in the WRN gene that is responsible for WS, among these patients. Instead, we found two novel heterozygous mutations at the junction of exon 10 and intron 11 of the LMNA gene. These mutations resulted in the production of progerin at a level substantially lower than that of HGPS. Our findings indicate that LMNA mutations may result in coronary artery disease presenting in the fourth to sixth decades along with short stature and a progeroid appearance resembling WS. The absence of early-onset cataracts in this setting should suggest the diagnosis of progeroid laminopathy. This study illustrates the evolving genotype-phenotype relationship between the amount of progerin produced and the age of onset among the spectrum of restrictive dermopathy, HGPS, and atypical forms of WS. PMID- 22065503 TI - catena-Poly[[diaqua-strontium]-bis-(MU-quinoline-3-carboxyl-ato)]. AB - The title compound, [Sr(C(10)H(6)NO(2))(2)(H(2)O)(2)](n), contains an eight coordinate Sr(II) ion displaying a distorted square-anti-prismatic geometry, two quinoline-3-carboxyl-ate ligands and two terminal water mol-ecules. The Sr(II) atom is surrounded by six carboxyl-ate O atoms from four separate quinoline-3 carboxyl-ate ligands and two O atoms from two coordinated water mol-ecules. The bridging carboxyl-ate O atoms [Sr-O = 2.498 (3) and 2.495 (3) A] link Sr(II) atoms, forming a chain substructure extending along the c axis. The chains are linked by O-H?N and O-H?O hydrogen bonds, giving a three-dimensional framework structure. PMID- 22065504 TI - 5-Cyclo-pentyl-2-methyl-3-phenyl-sulfonyl-1-benzofuran. AB - In the title compound, C(20)H(20)O(3)S, the cyclo-pentyl ring adopts an envelope conformation. The phenyl ring makes a dihedral angle of 81.40 (6) degrees with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds and C-H?pi inter-actions. PMID- 22065505 TI - (2R)-2-(1,3-Dioxoisoindolin-2-yl)-3-methyl-butanoic acid. AB - In the title compound, C(13)H(13)NO(4), the dihedral angle between the nine membered phthalimino ring system and the carb-oxy-lic acid group is 67.15 (9) degrees . An intra-molecular C-H?O close contact, which forms an S(6) ring, may help to establish the mol-ecular conformation. In the crystal, mol-ecules are linked by O-H?O hydrogen bonds, thereby forming C(7) chains propagating in [010]. PMID- 22065506 TI - 5-Hy-droxy-3,4',6,7-tetra-meth-oxy-flavone. AB - The title compound, C(19)H(18)O(7) [systematic name 5-hy-droxy-3,6,7-tri-meth- oxy-2-(4-meth-oxy-phen-yl)-4H-1-benzopyran-4-one], is a flavonoid which was isolated from the traditional Chinese medicine Laggera alata. The benzene ring of the benzopyran-one unit forms dihedral angles of 1.72 (3) and 37.39 (5) degrees with the pyran ring and the substituent benzene ring, respectively. The mol ecular conformation is stabilized by an intra-molecular phenol O-H?O(ketone) hydrogen bond. PMID- 22065507 TI - 2,4-Diamino-5-(4-chloro-phen-yl)-6-ethyl-pyrimidin-1-ium 2-propanamido-benzoate. AB - In the title salt, C(12)H(14)ClN(4) (+).C(10)H(10)NO(3) (-), zwitterionic N-H?O inter-actions form an R(2) (2)(8) ring. The crystal structure is stabilized by N H?O and N-H?N hydrogen bonds involving two different eight-membered rings. An N H?O inter-action occurs between the pyrimidine ring (donor) and carboxyl-ate group (acceptor) while the other ring is formed by N-H?N inter-actions, which form a dimer between two symmetry-related salts. An intra-molecular N-H?O hydrogen bond forms a six-membered ring in the benzoate. Inter-molecular C-H?O inter-actions are also observed. PMID- 22065508 TI - (2E)-1-(2,4-Dimethyl-quinolin-3-yl)-3-(thio-phen-2-yl)prop-2-en-1-one. AB - Two independent but virtually identical mol-ecules comprise the asymmetric unit in the title compound, C(18)H(15)NOS. With reference to the quinolin-3-yl group, the 3-(thio-phen-2-yl)prop-2-en-1-one residue is almost perpendicular, with all but the carbonyl O atom lying to one side of the plane. This conformation is reflected by the C-C-C-C torsion angles of -102.2 (3) and 81.1 (3) degrees in the two independent mol-ecules. The dihedral angle formed between the 13 non-H atoms directly associated with the quinolin-3-yl group and the thio-phen-2-yl ring is 87.70 (11) degrees [83.85 (10) degrees for the second independent mol ecule]. The presence of C-H?O, C-H?N and pi-pi inter-actions [centroid-centroid distance = 3.5590 (12) A] lead to supra-molecular chains along the c-axis direction. These are connected along the a-axis direction by C-H?pi inter actions. The resultant supra-molecular layers stack along the b axis. PMID- 22065509 TI - What line drawings reveal about the visual brain. AB - Scenes in the real world carry large amounts of information about color, texture, shading, illumination, and occlusion giving rise to our perception of a rich and detailed environment. In contrast, line drawings have only a sparse subset of scene contours. Nevertheless, they also trigger vivid three-dimensional impressions despite having no equivalent in the natural world. Here, we ask why line drawings work. We see that they exploit the underlying neural codes of vision and they also show that artists' intuitions go well beyond the understanding of vision found in current neurosciences and computer vision. PMID- 22065510 TI - 2,2'-[(1E)-3-Phenyl-prop-2-ene-1,1-di-yl]bis-(3-hy-droxy-5,5-dimethyl-cyclo-hex-2 en-1-one). AB - In the title mol-ecule, C(25)H(30)O(4), the two cyclo-hexene rings adopt envelope conformations. The two hy-droxy groups are involved in the formation of intra molecular O-H?O hydrogen bonds. In the crystal structure, weak inter-molecular C H?O hydrogen bonds link mol-ecules related by translation along the axis a into chains. PMID- 22065511 TI - CONTINUOUS-TIME FILTERS FOR STATE ESTIMATION FROM POINT PROCESS MODELS OF NEURAL DATA. AB - Neural spike trains, the primary communication signals in the brain, can be accurately modeled as point processes. For many years, significant theoretical work has been done on the construction of exact and approximate filters for state estimation from point process observations in continuous-time. We have previously developed approximate filters for state estimation from point process observations in discrete-time and applied them in the study of neural systems. Here, we present a coherent framework for deriving continuous-time filters from their discrete-counterparts. We present an accessible derivation of the well known unnormalized conditional density equation for state evolution, construct a new continuous-time filter based on a Gaussian approximation, and propose a method for assessing the validity of the approximation following an approach by Brockett and Clark. We apply these methods to the problem of reconstructing arm reaching movements from simulated neural spiking activity from the primary motor cortex. This work makes explicit the connections between adaptive point process filters for analyzing neural spiking activity in continuous-time, and standard continuous-time filters for state estimation from continuous and point process observations. PMID- 22065512 TI - 4-Nitro-N-(3-nitro-phen-yl)benzamide. AB - The title compound, C(13)H(9)N(3)O(5), prepared as a solid derivative of 3-nitro analine via reaction with 4-nitro-benzoyl chloride, crystallizes in a chiral space group. The mol-ecule is non-planar with a dihedral angle of 26.1 (1) degrees between the two benzene rings. Both nitro groups are twisted slightly out of the plane of their corresponding benzene rings, making dihedral angles of 10.7 (4) and 13.5 (4) degrees . The mol-ecules are stacked along the a axis with benzene ring centroid-centroid distances of 3.8878 (6) A. In the crystal, inter molecular benzene C-H?O inter-actions involving one nitro group and the carbonyl group link the mol-ecules, forming chains along [001]. An additional set of aromatic C-H?O inter-actions with the second nitro group form chains along [101], connecting adjacent chains to create layers perpendicular to the b axis. PMID- 22065513 TI - 3,3'-Diallyl-1,1'-[o-phenyl-enebis(methyl-ene)]diimidazol-3-ium bis-(hexa-fluoro phosphate). AB - In the cation of the title mol-ecular salt, C(20)H(24)N(4) (2+).2PF(6) (-), the central benzene ring makes dihedral angles of 84.19 (7) and 79.10 (7) degrees with the pendant imidazole rings. In one of the hexa-fluoro-phosphate anions, the six F atoms are disordered over two sets of sites, with an occupancy ratio of 0.842 (3):0.158 (3). In the crystal, the cations and anions are linked by numerous C-H?F hydrogen bonds, thereby forming a three-dimensional network. PMID- 22065514 TI - A second monoclinic polymorph of bis-(2,2'-bipyridine-kappaN,N')diiodido manganese(II). AB - The Mn(II) ion in the title complex, [MnI(2)(C(10)H(8)N(2))(2)], is six coordinated in a distorted cis-N(4)I(2)Mn octa-hedral environment by four N atoms of the two chelating 2,2'-bipyridine ligands and two iodide anions. As a result of the different trans effects of the N and I atoms, the Mn-N bonds trans to the I atom are slightly longer than the Mn-N bonds trans to the N atom. The dihedral angle between the approximately planar ligands [maximum deviation = 0.064 (7) A] is 75.0 (1) degrees . Numerous inter- and intra-molecular pi-pi inter-actions between the pyridyl rings are present, the shortest centroid-centroid distance being 3.905 (5) A. The structure reported herein represents a new monoclinic polymorph of the previously reported monoclinic (P2(1)/c) form [Ha (2011 ?). Z. Kristallogr. New Cryst. Struct.226, 187-188]. PMID- 22065515 TI - Effects of camptothecin and hydroxycamptothecin on insect cell lines Sf21 and IOZCAS-Spex-II. AB - BACKGROUND: In recent years, concerns over the potential impact of synthetic pesticides on the environment have made the discovery and development of environmentally friendly pesticides a more pressing issue. Camptothecin (CPT) and its derivatives have attracted much attention owing to their unique mechanisms of action against insects. In this paper, two insect cell lines, Sf21 and IOZCAS Spex-II, were used to conduct a preliminary investigation of the potential of CPT and hydroxycamptothecin (HCPT) as inducers of apoptosis in insect cell lines, and to illustrate the mechanism of action of CPT on insects at the cellular level. RESULTS: The results showed that both CPT and HCPT demonstrate potent cytotoxic effects to the tested insect cell lines in a time- and dose-dependent manner. The DNA fragmentation, activation of caspases and cytochrome c release were observed in both IOZCAS-Spex-II and Sf21 treated with CPT and HCPT. There is no significant difference in cytotoxicity and caspase-3 activation (P < 0.05, except when treated for 2 h) between CPT and HCPT, although the caspase-3 activation was slightly stronger when treated with HCPT in both Sf21 and IOZCAS-Spex-II. CONCLUSION: The results confirm the existence of the mitochondrial-dependent pathway of apoptosis induced by CPT and HCPT in Sf21 and IOZCAS-Spex-II cell lines. Further investigations are required to reveal the mitochondrial mechanisms and regulation of caspase activation during apoptosis. These studies will provide basic knowledge needed to understand the mechanisms of action of CPT and to develop CPT and its derivatives as insecticides. PMID- 22065516 TI - (E)-1-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-3-(4-fluoro-phen-yl)prop-2-en-1 one. AB - The asymmetric unit of the title compound, C(19)H(16)FN(3)O, contains two crystallographically independent mol-ecules. The triazole rings in both mol ecules are essentially planar with maximum deviations of 0.002 (1) and 0.001 (1) A. The dihedral angles between the benzene and fluorophenyl rings are 79.36 (9) and 89.40 (10) degrees in the two molecules. In the crystal, the two independent mol-ecules are linked by C-H?N hydrogen bonds, forming dimers. Furthermore, the crystal structure is stabilized by C-H?pi inter-actions. PMID- 22065517 TI - 2-Amino-4-methyl-6-oxo-3,6-dihydro-pyrimidin-1-ium perchlorate-2-amino-6-methyl pyrimidin-4(1H)-one-water (1/1/1). AB - In the title compound, C(5)H(8)N(3)O(+).ClO(4) (-).C(5)H(7)N(3)O.H(2)O, each perchlorate anion is paired with a protonated cationic 2-amino-6-methyl-pyrimidin 4(1H)-one and another non-protonated entity of the same organic pyrimidinone. The crystal structure is stabilized by N-H?O(org), N-H?O(water), N-H?O(ClO4), O H?O(ClO4), N-H?N and C-H?O(ClO4) hydrogen bonds between the anions, organic entities and water mol-ecules. Inter-molecular pi-pi stacking inter-actions between neighbouring organic rings are observed with a face-to-face distance of 3.776 (2) A, and O-H?O hydrogen bonds link the perchlorate anions and the water mol-ecules into chains along the b-axis direction. The perchlorate anion and the inter-stitial water mol-ecule are disordered over two mutually incompatible positions with a common occupancy ratio of 0.678 (16):0.322 (16). PMID- 22065518 TI - 3,4-Bis[4-(4-meth-oxy-phen-oxy)phen-yl]-1-methyl-1H-pyrrole-2,5-dione. AB - The title compound, C(31)H(25)NO(6), has a structure related to other 3,4-diaryl substituted maleic anhydride derivatives which have been shown to be useful as photochromic materials. The dihedral angles between the maleimide ring system and the benzene rings bonded to it are 44.48 (3) and 17.89 (3) degrees , while the angles between each of the latter rings and the corresponding ether bridging connected meth-oxy-benzene rings are 78.61 (8) and 72.67 (7) degrees . In the crystal, the molecules are linked by C-H?O inter-actions. PMID- 22065519 TI - Clinical efficacy of paclitaxel/cisplatin as an adjuvant chemotherapy for patients with cervical cancer who underwent radical hysterectomy and systematic lymphadenectomy. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to compare the clinical efficacy of paclitaxel/cisplatin (TP) as an adjuvant chemotherapy to adjuvant radiotherapy (RT) after radical hysterectomy and systematic lymphadenectomy for patients with cervical cancer. METHODS: A total of 125 patients with early-stage cervical cancer, who underwent radical hysterectomy, and received adjuvant therapy due to recurrent risk factors were retrospectively analyzed. Forty-nine patients were treated with RT, and 32 received paclitaxel/cisplatin (TP) for three to six cycles at 4-week interval. Survival and postoperative complications were compared between two modalities. RESULTS: There was no significant difference of 3-year disease-free survival between two groups (P = 0.23), while significantly better 3-year overall survival in TP group than RT group (P = 0.02). Seven of 32 patients (21.9%) treated with adjuvant TP, 16 of 49 patients (32.7%) treated with RT showed disease recurrence. Median of survival time after recurrence in RT group and TP group was 8.5 months, 12.0 months, respectively. Postoperative bowel obstruction was significantly more frequent in the RT group compared to the TP group (P = 0.01). CONCLUSIONS: Postoperative chemotherapy using TP might be more beneficial for survival than adjuvant RT and can reduce postoperative complications for cervical cancer patients treated with radical hysterectomy. PMID- 22065520 TI - Changing sociodemographic and clinical profile of patients attending a general hospital psychiatric clinic: some indications of community acceptance. AB - Demographic and clinical variables of first one thousand new patients attending a general hospital psychiatric clinic during each of the two years 1967 and 1977, were compared. The profile of a typical patient seems to have undergone a marked change over the decade. More patients are low drawn from lower income and occupational categories and the proportion of rural patients has increased. Proportion or acute psychiatric presentation particularly acute psychosis has increased markedly. Follow up rate has improved. All these indicate an increasing acceptance of this facility by the community and a better psychiatric awareness. PMID- 22065521 TI - (E)-4-{[(3-Propyl-5-sulfanyl-idene-4,5-dihydro-1H-1,2,4-triazol-4-yl)imino]-meth yl}-3-(p-tol-yl)-1,2,3-oxadiazol-3-ium-5-olate. AB - The title compound, C(15)H(16)N(6)O(2)S, exists in a trans configuration with respect to the acyclic N=C bond. The 1,2,3-oxadiazol-3-ium ring makes dihedral angles of 10.59 (8) and 73.94 (8) degrees , respectively, with the 1,2,4-triazole and benzene rings. The mol-ecular structure is stabilized by an intra-molecular C H?S hydrogen bond, which generates an S(6) ring motif. In the crystal, mol-ecules are linked into inversion dimers by pairs of inter-molecular N-H?S hydrogen bonds, generating eight-membered R(2) (2)(8) ring motifs. The dimers are further connected by C-H?O hydrogen bonds, forming a sheet parallel to the bc plane. The ethyl group is disordered over two sets of sites with occupancies of 0.744 (7) and 0.256 (7). PMID- 22065522 TI - A new support measure to quantify the impact of local optima in phylogenetic analyses. AB - Phylogentic analyses are often incorrectly assumed to have stabilized to a single optimum. However, a set of trees from a phylogenetic analysis may contain multiple distinct local optima with each optimum providing different levels of support for each clade. For situations with multiple local optima, we propose p support which is a clade support measure that shows the impact optima have on a final consensus tree. Our p-support measure is implemented in our PeakMapper software package. We study our approach on two published, large-scale biological tree collections. PeakMapper shows that each data set contains multiple local optima. p-support shows that both datasets contain clades in the majority consensus tree that are only supported by a subset of the local optima. Clades with low p-support are most likely to benefit from further investigation. These tools provide researchers with new information regarding phylogenetic analyses beyond what is provided by other support measures alone. PMID- 22065523 TI - Isopropyl 3-oxo-2,3-dihydro-1,2-benzothia-zole-2-carboxyl-ate. AB - The title compound, C(11)H(11)NO(3)S, was synthesized by the reaction of benzo[d]isothia-zol-3(2H)-one with isopropanol in toluene. The benzoisothia zolone ring system is essentially planar, with a mean deviation of 0.018 (2) A from the least-squares plane defined by the nine constituent atoms. In the crystal, mol-ecules are linked by weak inter-molecular C-H?O hydrogen bonds. PMID- 22065524 TI - A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia. AB - Autosomal recessive ataxias are heterogeneous group of disorders characterized by cerebellar atrophy and peripheral sensorimotor neuropathy. Molecular characterization of this group of disorders identified a number of genes contributing to these overlapping phenotypes. Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive form of ataxia caused by mutations in the SETX gene. We report on a consanguineous family with autosomal recessive inheritance and clinical characteristics of AOA2, and no mutations in the SETX gene. We mapped the AOA locus in this family to chromosome 17p12-p13. Sequencing of all genes in the refined region identified a homozygous missense mutation in PIK3R5 that was absent in 477 normal controls. Our characterization of the PIK3R5 protein and findings suggest that it may play a role in the development of the cerebellum and vermis. PMID- 22065525 TI - Clinical predictors of familial depression in Han Chinese women. AB - BACKGROUND: A number of clinical features potentially reflect an individual's familial vulnerability to major depression (MD), including early age at onset, recurrence, impairment, episode duration, and the number and pattern of depressive symptoms. However, these results are drawn from studies that have exclusively examined individuals from a European ethnic background. We investigated which clinical features of depressive illness index familial vulnerability in Han Chinese females with MD. METHODS: We used lifetime MD and associated clinical features assessed at personal interview in 1,970 Han Chinese women with DSM-IV MD between 30-60 years of age. Odds Ratios were calculated by logistic regression. RESULTS: Individuals with a high familial risk for MD are characterized by severe episodes of MD without known precipitants (such as stress life events) and are less likely to feel irritable/angry or anxious/nervous. CONCLUSIONS: The association between family history of MD and the lack of a precipitating stressor, traditionally a characteristic of endogenous or biological depression, may reflect the association seen in other samples between recurrent MD and a positive family history. The symptomatic associations we have seen may reflect a familial predisposition to other dimensions of psychopathology, such as externalizing disorders or anxiety states. PMID- 22065526 TI - Where do we come from? What are we? Where are we going? PMID- 22065527 TI - Evidence that autistic traits show the same etiology in the general population and at the quantitative extremes (5%, 2.5%, and 1%). AB - CONTEXT: Genetic factors play an important role in the etiology of both autism spectrum disorders and autistic traits. However, little is known about the etiologic consistency of autistic traits across levels of severity. OBJECTIVE: To compare the etiology of typical variation in autistic traits with extreme scoring groups (including top 1%) that mimicked the prevalence of diagnosed autism spectrum disorders in the largest twin study of autistic traits to date. DESIGN: Twin study using phenotypic analysis and genetic model-fitting in the total sample and extreme scoring groups (top 5%, 2.5%, and 1%). SETTING: A nationally representative twin sample from the general population of England. PARTICIPANTS: The families of 5968 pairs aged 12 years old in the Twins' Early Development Study. Main Outcome Measure Autistic traits as assessed by the Childhood Autism Spectrum Test. RESULTS: Moderate to high heritability was found for autistic traits in the general population (53% for females and 72% for males). High heritability was found in extreme-scoring groups. There were no differences in heritability among extreme groups or between the extreme groups and the general population. A continuous liability shift toward autistic trait affectedness was seen in the cotwins of individuals scoring in the top 1%, suggesting shared etiology between extreme scores and normal variation. CONCLUSION: This evidence of similar etiology across normal variation and the extremes has implications for molecular genetic models of autism spectrum disorders and for conceptualizing autism spectrum disorders as the quantitative extreme of a neurodevelopmental continuum. PMID- 22065528 TI - Brain gray matter deficits at 33-year follow-up in adults with attention deficit/hyperactivity disorder established in childhood. AB - CONTEXT: Volumetric studies have reported relatively decreased cortical thickness and gray matter volumes in adults with attention-deficit/hyperactivity disorder (ADHD) whose childhood status was retrospectively recalled. We present, to our knowledge, the first prospective study combining cortical thickness and voxel based morphometry in adults diagnosed as having ADHD in childhood. OBJECTIVES: To test whether adults with combined-type childhood ADHD exhibit cortical thinning and decreased gray matter in regions hypothesized to be related to ADHD and to test whether anatomic differences are associated with a current ADHD diagnosis, including persistent vs remitting ADHD. DESIGN: Cross-sectional analysis embedded in a 33-year prospective follow-up at a mean age of 41.2 years. SETTING: Research outpatient center. PARTICIPANTS: We recruited probands with ADHD from a cohort of 207 white boys aged 6 to 12 years. Male comparison participants (n = 178) were free of ADHD in childhood. We obtained magnetic resonance images in 59 probands and 80 comparison participants (28.5% and 44.9% of the original samples, respectively). MAIN OUTCOME MEASURES: Whole-brain voxel-based morphometry and vertexwise cortical thickness analyses. RESULTS: The cortex was significantly thinner in ADHD probands than in comparison participants in the dorsal attentional network and limbic areas (false discovery rate < 0.05, corrected). In addition, gray matter was significantly decreased in probands in the right caudate, right thalamus, and bilateral cerebellar hemispheres. Probands with persistent ADHD (n = 17) did not differ significantly from those with remitting ADHD (n = 26) (false discovery rate < 0.05). At uncorrected P < .05, individuals with remitting ADHD had thicker cortex relative to those with persistent ADHD in the medial occipital cortex, insula, parahippocampus, and prefrontal regions. CONCLUSIONS: Anatomic gray matter reductions are observable in adults with childhood ADHD, regardless of the current diagnosis. The most affected regions underpin top-down control of attention and regulation of emotion and motivation. Exploratory analyses suggest that diagnostic remission may result from compensatory maturation of prefrontal, cerebellar, and thalamic circuitry. PMID- 22065529 TI - Depression and history of attempted suicide as risk factors for heart disease mortality in young individuals. AB - CONTEXT: Although depression is associated with increased cardiovascular morbidity and mortality, there is virtually no information on whether it also increases the risk in young populations. OBJECTIVES: We sought to determine the association of unipolar and bipolar depression and a history of attempted suicide with mortality due to ischemic heart disease (IHD) and cardiovascular disease (CVD) in young US adults and to examine potential sex differences. DESIGN: Longitudinal epidemiologic study. SETTING: Nationally representative sample of US adults. PARTICIPANTS: A total of 7641 US adults aged 17 to 39 years from the 1988 1994 Third National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: Cardiovascular disease and IHD mortality. Unipolar/bipolar depression and a history of attempted suicide were assessed via the Diagnostic Interview Schedule. RESULTS: After a median follow-up of 14.9 years, a total of 51 subjects (0.67%) died of CVD causes and 28 (0.37%) died of IHD. Depression (538 individuals [7.04%]) and history of attempted suicide (419 [5.48%]) were each associated with an increased risk of IHD death, with adjusted hazard ratios of 3.70 (95% CI, 1.32-10.35) for depression and 7.12 (2.67-18.98) for a history of attempted suicide. Women with depression or a history of attempted suicide had a 3-fold adjusted risk of CVD (adjusted hazard ratio, 3.20 [95% CI, 1.12-9.17]) and a 14-fold adjusted risk of IHD (14.57 [2.65-80.10]). Corresponding figures for men were 2.37 (0.85-6.58) and 3.52 (1.05-11.76). CONCLUSION: In adults younger than 40 years, depression and history of attempted suicide are significant independent predictors of premature CVD and IHD mortality in both sexes. PMID- 22065530 TI - Protein binding in patients with late-life depression. AB - CONTEXT: Depression has been identified as a risk factor and a prodrome of dementia. Common neurobiological mechanisms may underlie this clinical and phenomenologic overlap. OBJECTIVE: To examine and compare protein (amyloid and tau) binding in critical brain regions in patients diagnosed as having late-life major depressive disorder (MDD) and healthy control individuals using 2-(1-{6-[(2 [(18)F]fluoroethyl)(methyl)-amino]-2-naphthyl}ethylidene) malononitrile ([(18)F]FDDNP) positron emission tomography. DESIGN: A cross-section neuroimaging study using positron emission tomography. SETTING: University of California, Los Angeles. Patients Our samples comprised 20 patients diagnosed as having MDD and 19 healthy control individuals of comparable age, sex, and educational level. Main Outcome Measure Relative distribution volume in regions of interest was used as the measure of [(18)F]FDDNP binding in all study participants. RESULTS: When compared with controls, [(18)F]FDDNP binding was significantly higher overall and in the posterior cingulate and lateral temporal regions in the MDD group. CONCLUSIONS: These findings suggest that neuronal injury associated with higher protein load in critical brain regions might provide a mechanism in the pathophysiologic manifestation of MDD in late life and have implications for the therapeutics of depression in elderly individuals. PMID- 22065531 TI - Personality disorders and the 3-year course of alcohol, drug, and nicotine use disorders. AB - CONTEXT: Little is known about the role of a broad range of personality disorders in the course of substance use disorder (SUD) and whether these differ by substance. The existing literature focuses mostly on antisocial personality disorder and does not come to clear conclusions. OBJECTIVE: To determine the association between the 10 DSM-IV personality disorders and the persistence of common SUDs in a 3-year prospective study of a national sample. DESIGN: Data were drawn from participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) who had alcohol dependence (n = 1172), cannabis use disorder (n = 454), or nicotine dependence (n = 4017) at baseline and who were reinterviewed 3 years later. Control variables included demographic characteristics, family history of substance disorders, baseline Axis I disorders and treatment status, and prior SUD duration. Main Outcome Measure Persistent SUD, defined as meeting full criteria for the relevant SUD throughout the 3-year follow-up period. RESULTS: Persistent SUD was found among 30.1% of participants with alcohol dependence, 30.8% with cannabis use disorder, and 56.6% with nicotine dependence at baseline. Axis I disorders did not have strong or consistent associations with persistent SUD. In contrast, antisocial personality disorder was significantly associated with persistent alcohol, cannabis, and nicotine use disorders (adjusted odds ratios, 2.46-3.51), as was borderline personality disorder (adjusted odds ratios, 2.04-2.78) and schizotypal personality disorder (adjusted odds ratios, 1.65-5.90). Narcissistic, schizoid, and obsessive-compulsive personality disorders were less consistently associated with SUD persistence. CONCLUSIONS: The consistent findings on the association of antisocial, borderline, and schizotypal personality disorders with persistent SUD indicates the importance of these personality disorders in understanding the course of SUD. Future studies should examine dimensional representations of personality disorders and the role of specific components of these disorders, biological and environmental contributors to these relationships, and potential applications of these findings to treatment development. PMID- 22065532 TI - Mirtazapine to reduce methamphetamine use: a randomized controlled trial. AB - CONTEXT: No approved pharmacologic treatments for methamphetamine dependence exist. Methamphetamine use is associated with high morbidity and is a major cofactor in the human immunodeficiency virus epidemic among men who have sex with men (MSM). OBJECTIVE: To determine whether mirtazapine would reduce methamphetamine use among MSM who are actively using methamphetamine. DESIGN: Double-blind, randomized, controlled, 12-week trial of mirtazapine vs placebo conducted from September 5, 2007, to March 4, 2010. SETTING: San Francisco Department of Public Health. PARTICIPANTS: Participants were actively using, methamphetamine-dependent, sexually active MSM seen weekly for urine sample collection and substance use counseling. INTERVENTIONS: Random assignment to daily oral mirtazapine (30 mg) or placebo; both arms included 30-minute weekly substance use counseling. MAIN OUTCOME MEASURES: The primary study outcome was reduction in methamphetamine-positive urine test results. Secondary outcomes were study medication adherence (by self-report and medication event monitoring systems) and sexual risk behavior. RESULTS: Sixty MSM were randomized, 85% of follow-up visits were completed, and 56 participants (93%) completed the final visit. In the primary intent-to-treat analysis, participants assigned to the mirtazapine group had fewer methamphetamine-positive urine test results compared with participants assigned to the placebo group (relative risk, 0.57; 95% CI, 0.35-0.93, P = .02). Urine positivity decreased from 67% (20 of 30 participants) to 63% (17 of 27) in the placebo arm and from 73% (22 of 30) to 44% (12 of 27) in the mirtazapine arm. The number needed to treat to achieve a negative weekly urine test result was 3.1. Adherence was 48.5% by medication event monitoring systems and 74.7% by self-report; adherence measures were not significantly different between arms (medication event monitoring systems, P = .82; self report, P = .92). Most sexual risk behaviors decreased significantly more among participants taking mirtazapine compared with those taking placebo (number of male partners with whom methamphetamine was used, P = .009; number of male partners, P = .04; episodes of anal sex with serodiscordant partners, P = .003; episodes of unprotected anal sex with serodiscordant partners, P = .003; episodes of insertive anal sex with serodiscordant partners, P = .001). There were no serious adverse events related to study drug or significant differences in adverse events by arm (P >= .99). CONCLUSION: The addition of mirtazapine to substance use counseling decreased methamphetamine use among active users and was associated with decreases in sexual risk despite low to moderate medication adherence. Trial Registration clinicalTrials.gov Identifier NCT00497081. PMID- 22065534 TI - Microdeletion of Xq28 involving the AFF2 (FMR2) gene in two unrelated males with developmental delay. AB - Fragile X E (FRAXE) is an X-linked form of intellectual disability characterized by mild to moderate cognitive impairment, speech delay, hyperactivity, and autistic behavior. The folate-sensitive fragile site FRAXE is located in Xq28 approximately 600 kb distal to the fragile X syndrome fragile site (FRAXA) and harbors an unstable GCC (CCG) triplet repeat adjacent to a CpG island in the 5' untranslated region of the AFF2 (FMR2) gene. The disorder results from amplification and methylation of the GCC repeat and resultant silencing of AFF2. Although chromosome abnormalities that disrupt AFF2 have been reported in two individuals with mild-moderate intellectual disability, microdeletions of Xq28 that delete only AFF2 have not been described as a potential cause of FRAXE intellectual disability. We performed clinical and molecular characterization of two males with 240 and 499 kb deletions, respectively, at Xq28, both of which encompassed only one gene, AFF2. The 240 kb deletion in Patient 1 was intragenic and lead to the loss of 5' exons 2-4 of AFF2; the 499 kb deletion in Patient 2 removed the 5' exons 1-2 of AFF2 including approximately 350 kb upstream of the gene. Both individuals had developmental and speech delay, and one had mild dysmorphism. We predict disruption of AFF2 in these two patients is likely the cause of their overlapping phenotypes. PMID- 22065533 TI - Racial/ethnic variations in substance-related disorders among adolescents in the United States. AB - CONTEXT: While young racial/ethnic groups are the fastest growing population in the United States, data about substance-related disorders among adolescents of various racial/ethnic backgrounds are lacking. OBJECTIVE: To examine the magnitude of past-year DSM-IV substance-related disorders (alcohol, marijuana, cocaine, inhalants, hallucinogens, heroin, analgesic opioids, stimulants, sedatives, and tranquilizers) among adolescents of white, Hispanic, African American, Native American, Asian or Pacific Islander, and multiple race/ethnicity. DESIGN: The 2005 to 2008 National Survey on Drug Use and Health. SETTING: Academic research. PARTICIPANTS: Noninstitutionalized household adolescents aged 12 to 17 years. MAIN OUTCOME MEASURES: Substance-related disorders were assessed by standardized survey questions administered using the audio computer-assisted self-interviewing method. RESULTS: Of 72 561 adolescents aged 12 to 17 years, 37.0% used alcohol or drugs in the past year; 7.9% met criteria for a substance-related disorder, with Native Americans having the highest prevalence of use (47.5%) and disorder (15.0%). Analgesic opioids were the second most commonly used illegal drugs, following marijuana, in all racial/ethnic groups; analgesic opioid use was comparatively prevalent among adolescents of Native American (9.7%) and multiple race/ethnicity (8.8%). Among 27 705 past-year alcohol or drug users, Native Americans (31.5%), adolescents of multiple race/ethnicity (25.2%), adolescents of white race/ethnicity (22.9%), and Hispanics (21.0%) had the highest rates of substance-related disorders. Adolescents used marijuana more frequently than alcohol or other drugs, and 25.9% of marijuana users met criteria for marijuana abuse or dependence. After controlling for adolescents' age, socioeconomic variables, population density of residence, self-rated health, and survey year, adjusted analyses of adolescent substance users indicated elevated odds of substance-related disorders among Native Americans, adolescents of multiple race/ethnicity, adolescents of white race/ethnicity, and Hispanics compared with African Americans; African Americans did not differ from Asians or Pacific Islanders. CONCLUSIONS: Substance use is widespread among adolescents of Native American, white, Hispanic, and multiple race/ethnicity. These groups also are disproportionately affected by substance related disorders. PMID- 22065535 TI - Screening of common bean (Phaseolus vulgaris) for resistance against temperate root-knot nematodes (Meloidogyne spp.). AB - BACKGROUND: An important part of the production area of common bean (Phaseolus vulgaris L.) in Belgium is located on the sandy soils of the provinces of Antwerp and Limburg where Meloidogyne chitwoodi (Golden), M. fallax (Karssen) and M. hapla (Chitwood) are present. The host plant status of ten bean cultivars for root-knot nematodes was determined by evaluating penetration, development and egg mass formation after inoculation with second-stage juveniles. RESULTS: The tested cultivars were poor to good hosts for M. chitwoodi, non-hosts or bad hosts for M. fallax and excellent hosts for M. hapla. Significantly fewer M. fallax were found in the roots, and their development was delayed. Penetration of M. hapla took place over a longer period than that of M. chitwoodi and M. fallax. The number of mature females of M. chitwoodi in cv. Polder 6 weeks after inoculation was no different from that in other cultivars, although fewer egg masses were found on this cultivar in the screening test. There was no influence of M. chitwoodi on vegetative growth of cv. Polder. CONCLUSION: The differences found in host plant status of bean cultivars stress the importance of a correct diagnosis of the Meloidogyne species in agricultural fields. Cultivar Polder showed potential as a trap crop for M. chitwoodi. PMID- 22065536 TI - The influence of postoperative glycemic control on recurrence after curative resection in diabetics with hepatitis C virus-related hepatocellular carcinoma. AB - BACKGROUND AND OBJECTIVES: To elucidate the influence of diabetes on tumor recurrence after curative resection for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODS: A total of 100 patients who underwent curative resection for solitary HCV-related HCC were analyzed. Data from 26 patients with diabetes were compared to those of 74 patients without diabetes. The two groups were matched in terms of presence of cirrhosis, Child-Pugh classification, and tumor size (within 10%). RESULTS: Tumor-free survival rates were 45% and 48% at 3 years and 27% and 27% at 5 years in patients with and without diabetes, respectively. No significant difference was observed in the tumor-free survival rates between patients with and without diabetes. Tumor-free survival rates were 66% and 27% at 3 years in patients with normal postoperative glycated hemoglobin (HbA1c) level (HbA1c, <6.5%) and elevated postoperative HbA1c level (HbA1c, >=6.5%), respectively. Multivariate analysis showed that poor glycemic control (HbA1c, >=6.5%) was associated with postoperative tumor recurrence in patients with diabetes [odds ratio (OR) = 3.551, 95% confidence interval (CI) = 1.129-11.172, P = 0.030]. CONCLUSIONS: Careful control of plasma glucose should be performed to prevent tumor recurrence after curative resection for HCV-related HCC in patients with diabetes. PMID- 22065537 TI - Memory dysfunction in panic disorder: an investigation of the role of chronic benzodiazepine use. AB - BACKGROUND: Studies of the neurocognitive effects of long-term benzodiazepine use have been confounded by the presence of neurocognitive deficits characterizing the clinical conditions for which these medications are taken. Similarly, studies of the neurocognitive effects of anxiety disorders have been confounded by the inclusion of chronically benzodiazepine-medicated patients. This study was designed to tease apart the potentially confounding effects of long-term benzodiazepine use and panic disorder (PD) on memory and visuoconstructive abilities. METHODS: Twenty chronically benzodiazepine-medicated and 20 benzodiazepine-free patients with PD with agoraphobia were compared with a group of 20 normal control participants, group-matched for age, education, and gender on a battery of neuropsychological tests assessing short-term, episodic long term, and semantic memory, as well as visuoconstructive abilities. RESULTS: Results indicated that benzodiazepine-free panic patients were relatively impaired in nonverbal short-term and nonverbal episodic long-term memory and visuoconstructive abilities, whereas verbal short-term and verbal episodic memory and semantic memory were preserved. Only limited evidence was found for more pronounced impairments in chronically benzodiazepine-medicated PD patients. CONCLUSIONS: This study provides evidence that patients with PD are characterized by relative impairments in nonverbal memory and visuoconstructive abilities, independent of benzodiazepine use. Nonetheless, we found evidence that chronic treatment with benzodiazepines is associated with intensification of select relative impairments in this realm. Documentation of these deficits raises questions about the broader etiology of neurocognitive impairment in PD as well as its impact on daily functioning. PMID- 22065538 TI - CDH13 gene coding T-cadherin influences variations in plasma adiponectin levels in the Japanese population. AB - Adiponectin is most abundantly expressed in adipose tissue and well known to play an important role in metabolic regulation. Several studies have attempted to identify the genetic determinants of metabolic syndrome (MetS), though no study has revealed a cis- or trans-single nucleotide polymorphism (SNP) that affects plasma adiponectin levels, except the adiponectin structure gene and genes encoding adiponectin-regulatory proteins. We performed a genome-wide association study in regards to plasma adiponectin concentrations in 3,310 Japanese subjects. We identified the strongest statistically associated SNP (rs4783244) with adiponectin levels (P = 3.8 * 10(-19)) in the first intron of CDH13 (T-cadherin) gene in a 30-kb haplotype block covering the promoter region to first intron. In addition, rs12051272 SNP genotypes in linkage disequilibrium with rs4783244 were found to be more significantly associated with adiponectin levels (P = 9.5*10( 20)) and specifically with the levels of high-molecular weight (HMW) adiponectin, a subtype form associated with parameters related to glucose metabolism. Our results did show more significant association with adiponectin levels than rs12444338 (in CDH13) SNP genotypes reported recently. We suggest that the phenotype-affecting haplotype tagged by rs12051272 SNP would affect the plasma adiponectin levels and that we have to take the CDH13 genotype into account before considering the functional relevance of the adiponectin level. PMID- 22065539 TI - 5-Cyclo-pentyl-2-(4-fluoro-phen-yl)-3-methyl-sulfinyl-1-benzofuran. AB - In the title compound, C(20)H(19)FO(2)S, the cyclo-pentyl ring adopts an envelope conformation. The 4-fluoro-phenyl ring makes a dihedral angle of 27.10 (7) degrees with the mean plane of the benzofuran fragment. In the crystal, mol ecules are linked by weak inter-molecular C-H?O hydrogen bonds and C-H?pi inter actions. In the cyclo-pentyl ring, one C atom is disordered over two orientations with site-occupancy factors of 0.617 (7) and 0.383 (7). PMID- 22065540 TI - Split hand-split foot-ectodermal dysplasia and amelogenesis imperfecta with a TP63 mutation. AB - We report on a mother and son who were affected with split hand-split foot (formerly described as ectrodactyly), ectodermal dysplasia, hyperpigmentation of skin, and dystrophic nails. Their hair was wiry, brownish, and slow-growing. Scanning electron micrography of their scalp hair showed hypoplastic hair bulbs, partial loss of hair cuticles, and frayed hair shafts. The son was affected with amelogenesis Imperfecta (hypocalcification, hypoplasia, and hypomaturation types), in the primary and permanent dentition. An unerupted supernumerary maxillary second premolar and fusion of mandibular incisors were observed in the primary dentition and their permanent successors. Mutation analysis showed a c.588-2A > C mutation in TP63 in the mother and her son. It is predicted that an alternative splice site was used, specifically the AG located just three nucleotides upstream. Use of this site is predicted to include three extra nucleotides in the transcript and thus incorporation of a single extra amino acid (p.Thr195_Tyr196insPro). This is the first time that amelogenesis imperfecta, fusion of teeth, and a supernumerary premolar have been shown to be associated with a TP63 mutation. PMID- 22065541 TI - A novel structural position-specific scoring matrix for the prediction of protein secondary structures. AB - MOTIVATION: The precise prediction of protein secondary structure is of key importance for the prediction of 3D structure and biological function. Although the development of many excellent methods over the last few decades has allowed the achievement of prediction accuracies of up to 80%, progress seems to have reached a bottleneck, and further improvements in accuracy have proven difficult. RESULTS: We propose for the first time a structural position-specific scoring matrix (SPSSM), and establish an unprecedented database of 9 million sequences and their SPSSMs. This database, when combined with a purpose-designed BLAST tool, provides a novel prediction tool: SPSSMPred. When the SPSSMPred was validated on a large dataset (10,814 entries), the Q3 accuracy of the protein secondary structure prediction was 93.4%. Our approach was tested on the two latest EVA sets; accuracies of 82.7 and 82.0% were achieved, far higher than can be achieved using other predictors. For further evaluation, we tested our approach on newly determined sequences (141 entries), and obtained an accuracy of 89.6%. For a set of low-homology proteins (40 entries), the SPSSMPred still achieved a Q3 value of 84.6%. AVAILABILITY: The SPSSMPred server is available at http://cal.tongji.edu.cn/SPSSMPred/ CONTACT: lith@tongji.edu.cn PMID- 22065542 TI - Magnetic field-induced acceleration of the accumulation of magnetic iron oxide nanoparticles by cultured brain astrocytes. AB - Magnetic iron oxide nanoparticles (Fe-NPs) are considered for various biomedical and neurobiological applications that involve the presence of external magnetic fields. However, little is known on the effects of a magnetic field on the uptake of such particles by brain cells. Cultured brain astrocytes accumulated dimercaptosuccinate-coated Fe-NP in a time-, temperature-, and concentration dependent manner. This accumulation was strongly enhanced by the presence of the magnetic field generated by a permanent neodymium iron boron magnet that had been positioned below the cells. The magnetic field-induced acceleration of the accumulation of Fe-NP increased almost proportional to the strength of the magnetic field applied, increasing the cellular-specific iron content from an initial 10 nmol/mg protein within 4 h of incubation at 37 degrees C to up to 12,000 nmol/mg protein. However, presence of a magnetic field also increased the amounts of iron that attached to the cells during incubation with Fe-NP at 4 degrees C. These results suggest that the presence of an external magnetic field promotes in cultured astrocytes both the binding of Fe-NP to the cell membrane and the internalization of Fe-NP. PMID- 22065543 TI - Prognostic values of the miR-17-92 cluster and its paralogs in colon cancer. AB - BACKGROUND: MicroRNAs have been shown to offer great potential in both the diagnosis and prognosis of cancer. Despite the well-established role of the miR 17-92 in cancer formation and progression, the contribution of each individual miRNA remains to be characterized. Thus, we investigated whether deregulation of the miR-17-92 associated with colon cancer prognosis. METHODS: Expression levels of the miR-17-92 cluster and its paralogs were determined in 48 colon tumor and 48 paired normal tissues by real-time qRT-PCR. Associations with miRNA expression, age, sex, TNM staging, and survival prognosis were evaluated. RESULTS: MiR-17-92 cluster and its paralogs were significantly overexpressed in colon tumor. No significant associations were found between the deregulation of certain miRNAs and the clinical and pathologic characteristics observed in patients. Kaplan-Meier curves demonstrated significantly reduced overall survival in patients expressing high levels of miR-17. In multivariate Cox models, miR-17 overexpression (HR 2.67; P = 0.007) and TNM staging (HR 8.87; P = 0.002) were significantly associated with a risk of death. CONCLUSIONS: The miR-17-92 cluster and its paralogs were significantly elevated in patients with colon cancer, and heightened expression of miR-17 was associated with poor survival. Moreover, miR 17 and TNM staging were both identified as significant, but independent, prognostic biomarkers in colon cancer. PMID- 22065544 TI - Do patients with hoarding disorder have autistic traits? AB - BACKGROUND: Hoarding symptoms have been described in individuals with autism spectrum disorders (ASD). Furthermore, individuals with hoarding disorder (HD) may display some ASD-like features. In order to further refine the diagnostic boundaries of HD, we examined the presence of autistic traits and theory of mind deficits in individuals with HD and of hoarding behavior in patients with ASD. METHODS: Two hundred and twenty-one participants in five groups (HD, ASD, obsessive-compulsive disorder (OCD), anxiety disorders (AD), and healthy controls (HC)) were administered measures of autistic traits (Autism-Spectrum Quotient), theory of mind (eyes test-revised), and hoarding severity (saving inventory revised; SI-R (add acronym)). RESULTS: Hoarders displayed more autistic traits compared to healthy individuals but not to psychiatric controls. Participants with ASD had significantly higher scores on the SI-R than both psychiatric (OCD or AD) and HC groups, indicating more severe hoarding behavior, but had lower scores than participants with HD. The presence of autistic traits in individuals with HD was related to the presence of comorbid OCD, but the presence of hoarding symptoms in individuals with ASD was unrelated to comorbid OCD. CONCLUSIONS: We conclude that individuals with HD do not display more autistic traits than psychiatric controls, thus supporting its status as an independent diagnostic entity. More research is needed to further understand the phenomenology and clinical relevance of hoarding symptoms in ASD. PMID- 22065545 TI - CRB1 mutations in inherited retinal dystrophies. AB - Mutations in the CRB1 gene are associated with variable phenotypes of severe retinal dystrophies, ranging from leber congenital amaurosis (LCA) to rod-cone dystrophy, also called retinitis pigmentosa (RP). Moreover, retinal dystrophies resulting from CRB1 mutations may be accompanied by specific fundus features: preservation of the para-arteriolar retinal pigment epithelium (PPRPE) and retinal telangiectasia with exudation (also referred to as Coats-like vasculopathy). In this publication, we report seven novel mutations and classify over 150 reported CRB1 sequence variants that were found in more that 240 patients. The data from previous reports were used to analyze a potential correlation between CRB1 variants and the clinical features of respective patients. This meta-analysis suggests that the differential phenotype of patients with CRB1 mutations is due to additional modifying factors rather than particular mutant allele combination. PMID- 22065546 TI - Authors response to correspondence about an improved compensation method. PMID- 22065547 TI - 2,2-Diethyl 4-methyl 5-(4-nitro-phen-yl)-4-phenyl-pyrrolidine-2,2,4-tricarboxyl ate. AB - The title compound, C(24)H(26)N(2)O(8), was synthesized by the cyclo-addition reaction of methyl 2-phenyl-acrylate, diethyl 2-amino-malonate and 4-nitro benzaldehyde. The pyrrolidine ring exhibits an envelope conformation. The two benzene rings are located on opposite sides of the pyrrolidine ring and subtend a dihedral angle of 59.16 (14) degrees . The crystal packing is stabilized by N-H?O and weak C-H?O hydrogen bonding. PMID- 22065548 TI - Blood platelet adhesion to printed von Willebrand factor. AB - Von Willebrand factor (vWF), a glycoprotein in blood, mediates the adhesion of blood platelets and thus plays a crucial role in hemostasis and thrombosis. Functional coating of surfaces with vWF allows the investigation of in vitro adhesion of blood platelet. We used soft lithography to create a functional patterned substrate. vWF was printed on plasma-treated glass and mica surfaces, producing elongated network-like fibril structures. A minimum layer thickness of 3 nm was observed, corresponding to the height of a monolayer of vWF. The stability of the patterns was verified in a laminar fluid flow, and the bioactivity of the structures was tested with platelet adhesion experiments. Platelets adhered to and spread on printed vWF. These results indicate that printed vWF substrates are stable and functional in typical perfusion experiments, and thus provide a useful tool for studying thrombus formation in vitro. PMID- 22065549 TI - A prognostic model to predict outcome of patients failing to achieve pathological complete response after anthracycline-containing neoadjuvant chemotherapy for breast cancer. AB - BACKGROUND: The aim of this study was to evaluate factors that could possibly affect the outcome of patients failing to achieve pathological complete response (pCR) after anthracycline-containing neoadjuvant chemotherapy (NCT) for breast cancer, and built a prognostic model to predict patients' outcome. PATIENTS AND METHODS: Data from 199 stage II-III breast cancer patients who failed to achieve pCR after NCT were used. Variables at baseline and at surgery (age, menopausal status, tumour size, grade, histotype, node status, vascular invasion, ER, PR, HER-2, Cathepsin D, P53, Topo-IIalpha, Nm-23, Bcl-2, BAX, MDR, GSTN, PS2, P27, Cyclin D1 and Ki-67) were investigated. RESULTS: Tumour marker Ki-67, Cathepsin D status and number of positive lymph nodes at surgery were significant prognostic factors in multivariate analysis for both DFS and OS. According to our prognostic model, the 5-year DFS rates in low, intermediate-low, intermediate-high and high risk groups were 94%, 65%, 43% and 28%, respectively (log-rank test P < 0.001). The 5-year OS rates in these four groups were 94%, 84%, 66% and 34%, respectively (log-rank test P < 0.001). CONCLUSION: Our prognostic model could easily discriminate patients with different risks of experiencing an event or death, which could allow physicians to tailor treatment strategies specifically and individually. PMID- 22065550 TI - Investigation of telomere length and psychological stress in rape victims. AB - BACKGROUND: Women are at an increased risk of depression and other mental health problems following rape. Various etiological factors for depression, including predisposing genetic factors, have been identified. Telomeres are repetitive nucleoprotein structures located at chromosomal ends that protect them from premature degradation. Telomeres reduce in length with each cell division, resulting in cellular senescence and apoptosis. METHODS: Relative quantification of telomeric repeats using qPCR was performed to investigate whether shorter relative leukocyte telomere length (LTL) in a cohort of 64 rape victims was associated with resilience, the development of rape trauma-related major depressive disorder (MDD) or the development of posttraumatic stress disorder (PTSD) after 3 months. RESULTS: Out of the 64 participants, 23 participants were diagnosed with MDD at baseline and 31 after 3 months. Nine participants were diagnosed with PTSD (MDD and PTSD specifically related to the trauma). No significant associations were observed between relative LTL and resilience or the development of MDD at either baseline or after 3 months in this cohort. However, a marginally significant association was evident between relative LTL and PTSD status. CONCLUSIONS: The significant association between relative LTL and PTSD suggests that shorter relative LTL might have acted as a predisposing factor in the development of PTSD after a severely traumatic event. The results of this study indicate that telomere shortening may be an important marker of PTSD risk, with implications for early intervention and timely treatment, and as such warrant replication in a larger cohort. PMID- 22065551 TI - Effects of exposition to polluted environments on blood cells of the fish Prochilodus lineatus. AB - In this study, we investigated the effects of contaminated water on the blood parameters of the fish Prochilodus lineatus exposed during 7 and 20 days. Blood was collected with heparinized syringes, and blood smears were prepared and stained with Leishman stain. Slides were examined and photographed using a Leica light microscope. Total white blood cell counts and differential counts of thrombocytes and leukocytes were obtained for statistical analysis. The group exposed to water samples from Lago Azul exhibited an increase in the number of leukocytes and in the total number of white blood cells, suggesting that the chemical contaminants in this environment were acting similarly to antigens in this fish species, causing the proliferation of defense cells. In the group exposed to detergent during 20 days, the number of thrombocytes decreased. These results suggest that the variations in the number of leukocytes were indicators of environmental pollution and that biodegradable detergents may, after a certain time of exposure, affect vital functions in fish, such as coagulation and prevention of infections, which directly involves thrombocytes. PMID- 22065552 TI - Proteome profiling of the green sulfur bacterium Chlorobaculum tepidum by N terminal proteomics. AB - In this study, we performed the first large-scale identification of N-terminal peptides from the green sulfur bacterium Chlorobaculum tepidum. Combined fractional diagonal chromatography (COFRADIC) was used to isolate protein N terminal peptides from three different proteome preparations, and following LC MS/MS analysis, over 621 different proteins were identified by their N-terminal peptides. Our data constitute the largest data set currently available for protein N-termini of prokaryotic photosynthetic organisms. PMID- 22065553 TI - Micropatterned agarose scaffolds covalently modified with collagen for culture of normal and neoplastic hepatocytes. AB - Anchorage-dependent cells including hepatocytes, the main functional cellular constituent comprising liver tissue, require a substrate for cell adhesion when cultured outside their native tissue. The challenge with hepatocyte culture is that material substrates and designs supporting hepatocyte attachment, phenotype, and function are not readily available. Our laboratory previously published that type I collagen found in the liver extracellular matrix supports hepatocyte culture. We hypothesized that micropatterned agarose with a coating of collagen covalently bound to the surface would facilitate hepatocyte adhesion and phenotype. To test this hypothesis, primary canine hepatocytes and neoplastic human HepG2 hepatocellular carcinoma cells were cultured on these substrates. Hepatocyte adhesion was dependent on the cell type and also the micropattern design. Viable normal and neoplastic hepatocytes attached to the microchannel troughs rather than on the ridges. In contrast, hepatocyte adhesion on the microcircular patterns was similar to control agarose as cells did not sense differences in surface topology on these substrates. Neoplastic cells exhibited a distinct difference in growth behavior following 7 days in culture on the microchannel patterns, exhibiting aberrant proliferation relative to normal hepatocytes which did not proliferate. Our results suggest that patterned microchannel agarose may be useful to evaluate hepatoprotective and noxious agents. PMID- 22065554 TI - Treatment change of somatic symptoms and cultural syndromes among Cambodian refugees with PTSD. AB - BACKGROUND: There is only one previously published study of treatment change across initial pharmacological treatment for a minority or refugee group with posttraumatic stress disorder (PTSD). That study found that certain somatic symptoms among Southeast Asian populations did not improve across treatment. This article assesses in a culturally sensitive way symptom change through time of Cambodian patients presenting for pharmacotherapy treatment of PTSD. METHODS: Fifty-six Cambodian refugees with PTSD and no previous psychiatric treatment were assessed at baseline and then at 3 and 6 months after initiating pharmacotherapy. The measures included the PTSD Checklist; the Cambodian Somatic Symptom and Syndrome Inventory (SSI) to assess culturally salient somatic symptoms and cultural syndromes; and the Short Form-12 Health Survey to assess self-perceived functioning. RESULTS: Across treatment, large effect sizes were seen on all measures (Cohen's d = 1.1-1.4). The SF-12 change score was more highly correlated to the SSI change score (r = .82) than to the PTSD change score (r = .61). Significant change only occurred from baseline to 3 months. CONCLUSIONS: Pharmacological treatment for traumatized Cambodian refugees with PTSD seems to lead to improvement not only in PTSD symptoms, but also in culturally salient somatic symptoms and cultural syndromes. Culturally sensitive assessment and treatment should ideally include the assessment of culturally salient somatic symptoms and cultural syndromes. PMID- 22065555 TI - B-flow imaging for the measurement of residual lumen diameter of renal artery stenosis. AB - BACKGROUND: The aim of this study was to assess the accuracy and efficacy of B flow imaging (BFI) in the diagnosis and measurement of renal artery stenosis (RAS) compared with color duplex ultrasonography (CDU) and digital subtraction angiography (DSA). METHODS: Fifty-one consecutive patients with RAS diagnosed and measured with DSA were subsequently and independently examined with BFI for the measurement of residual lumen diameter, and with CDU for the measurement of peak systolic velocity and renal-aortic velocity ratio. The diagnostic performances of BFI and CDU in determining 60-99% RAS were compared by receiver operating characteristic curve analysis. The agreement between DSA and BFI stenosis measurements was evaluated with Bland-Altman method. RESULTS: The area under curve was 0.983 for BFI and 0.959 for CDU, without a significant difference in diagnostic performances (p = 0.26). BFI yielded an 88% sensitivity and 94% specificity in the diagnosis of RAS with a 3% underestimation of RAS compared to DSA (95% confidence interval 1.4%, 4.6%). CONCLUSIONS: BFI is an accurate method that minimally underestimates RAS. It might provide an additional benefit to CDU in patients with RAS. PMID- 22065556 TI - Analysis of proteome and frost tolerance in chromosome 5A and 5B reciprocal substitution lines between two winter wheats during long-term cold acclimation. AB - Dynamics of cold tolerance and crown proteome composition has been analysed in a set of two winter wheat cultivars Mironovskaya 808 and Bezostaya 1 and four reciprocal substitution lines with interchanged chromosomes 5A and 5B during a long-term cold-acclimation (CA) treatment. Proteome analysis has revealed 298 differently abundant spots during experiment. Most of them (260) were changed due to CA process and only 52 spots displayed differences between genotypes. Two hundred and seven protein spots were successfully identified by tandem mass spectrometry. Comparison of samples before and after vernalization fulfillment by a combination of ANOVA and Student' T-test displayed ten differentially abundant protein spots (e.g. chopper chaperones). However, differences in the accumulation of these spots did not reflect differences in vernalization requirement of genotypes. Therefore, our results indicate that vernalization process has not influenced total proteome of CA wheat crowns. A few protein spots (14 spots; e.g. malate dehydrogenase) revealed differential accumulation levels between the individual genotypes or their groups possessing chromosome 5A or 5B from Mironovskaya 808 versus Bezostaya 1. The study has shown the effect of chromosome 5A on physiological traits and also proteome in winter wheat. Putative candidate protein markers for cold tolerance in wheat are discussed. PMID- 22065557 TI - 1-(3,4-Dimeth-oxy-phen-yl)propan-1-one. AB - The title compound, C(11)H(14)O(3), was isolated from the stems of Trigonostemon xyphophylloides, which belongs to Trigonostemon genus of Euphorbiaceae. The plants in this genus were used in folk medicine, such as for the treatment of diseases caused by viruses and fungi. The limited investigation of the chemistry of this plant prompted an examination of constituents of its twigs, from which the title compound was isolated. The mol-ecule is approximately planar with an r.m.s. deviation of 0.1237A. In the crystal, inter-molecular C-H?O hydrogen bonds connect the mol-ecules into a two-dimensional network structure with an R(2) (2)(12) graph-set motif. PMID- 22065558 TI - 1,2-Bis(benz-yloxy)-1,2-bis-(4-chloro-phen-yl)-3,8-dimeth-oxy-acenaphthene. AB - In the title compound, C(40)H(32)Cl(2)O(4), the two chloro-benzene rings are in syn orientations with respect to the naphthalene ring system and make dihedral angles of 57.12 (6) and 85.74 (6) degrees with it. The benzene rings of the benz yloxy group make dihedral angles of 75.34 (6) and 83.95 (7) degrees , with the naphthalene ring system. In the crystal, the mol-ecules are linked by inter molecular C-H?Cl inter-actions between the methyl-ene H atoms of the benz-yloxy group and the Cl atoms in adjacent mol-ecules. Furthermore, centrosymmetrically related mol-ecules are linked into dimeric units by pairs of C-H?pi inter actions. PMID- 22065559 TI - Optimization of poly(epsilon-caprolactone) surface properties for apatite formation and improved osteogenic stimulation. AB - A biodegradable polymer with surface properties that promotes cell attachment and host integration is widely recognized as a useful three-dimensional construct for bone tissue engineering applications. In this work, studies were carried out to correlate surface properties of modified polycaprolactone (PCL) films with cell material interactions. PCL film substrates were subjected to various degrees of chemical hydrolysis using different pretreatment solutions to introduce different densities of carboxylate groups onto the surfaces. The extent of hydrolysis on the films was optimized to allow the deposition of a dense and uniform bone-like apatite layer by an alternate soak treatment, followed by subsequent incubation in simulated body fluid (SBF). The hydrolyzed and apatite-coated PCL films were investigated using scanning electron microscopy, thin film X-ray diffractometer (TF-XRD), water contact angle, and Alizarin red staining. Surface wettability, roughness, and chemistry of various PCL substrates were correlated with cell attachment, proliferation, viability, and alkaline phosphatase activity. Results demonstrated that cell attachment increased with increasing surface hydrophilicity and roughness. The apatite-coated films showed significantly improved surface wettability and enhanced surface roughness, which subsequently led to better cell attachment potential, high-cell viability, and enhanced bone formation capability. Thus, surface modification with an apatite coating layer is a promising approach for enhancing the efficacy of the polymeric scaffold for bone tissue engineering applications. PMID- 22065560 TI - Childhood maltreatment and social anxiety disorder: implications for symptom severity and response to pharmacotherapy. AB - BACKGROUND: Childhood maltreatment has been associated with symptom severity, reduced quality of life, and impaired functioning in adults with social anxiety disorder (SAD). No study has investigated how childhood maltreatment impacts pharmacotherapy outcomes in this population, despite evidence for such a link in depression. The current study replicates previous work on childhood maltreatment within SAD and examines its impact on response to pharmacotherapy. METHODS: One hundred and fifty six individuals seeking treatment for SAD completed the Childhood Trauma Questionnaire, which measures various types of abuse and neglect, along with the measures of symptom severity, quality of life, and disability. Data from a subset of patients enrolled in a paroxetine trial (N = 127) were analyzed to gauge the impact of childhood maltreatment on attrition and treatment response. RESULTS: All types of maltreatment except for sexual abuse and physical abuse were related to greater symptom severity. Emotional abuse and neglect were related to greater disability, and emotional abuse, emotional neglect, and physical abuse were related to decreased quality of life. Emotional abuse significantly predicted attrition. A time by emotional abuse interaction suggests that for those who stayed the course, the impact of emotional abuse on severity of social anxiety weakened significantly over time. CONCLUSIONS: Emotional maltreatment was most strongly linked to dysfunction in SAD, despite a tendency in the anxiety literature to focus on the effects of sexual and physical abuse. Additionally, individuals reporting emotional abuse were more likely to dropout from pharmacotherapy, but those who stayed the course displayed similar outcomes to those without such a history. PMID- 22065561 TI - Multiclass mycotoxin analysis in food, environmental and biological matrices with chromatography/mass spectrometry. AB - Mold metabolites that can elicit deleterious effects on other organisms are classified as mycotoxins. Human exposure to mycotoxins occurs mostly through the intake of contaminated agricultural products or residues due to carry over or metabolite products in foods of animal origin such as milk and eggs, but can also occur by dermal contact and inhalation. Mycotoxins contained in moldy foods, but also in damp interiors, can cause diseases in humans and animals. Nephropathy, various types of cancer, alimentary toxic aleukia, hepatic diseases, various hemorrhagic syndromes, and immune and neurological disorders are the most common diseases that can be related to mycotoxicosis. The absence or presence of mold infestation and its propagation are seldom correlated with mycotoxin presence. Mycotoxins must be determined directly, and suitable analytical methods are necessary. Hundreds of mycotoxins have been recognized, but only for a few of them, and in a restricted number of utilities, a maximum acceptable level has been regulated by law. However, mycotoxins seldom develop alone; more often various types and/or classes form in the same substrate. The co-occurrence might render the individual mycotoxin tolerance dose irrelevant, and therefore the mere presence of multiple mycotoxins should be considered a risk factor. The advantage of chromatography/mass spectrometry (MS) is that many compounds can be determined and confirmed in one analysis. This review illustrates the state-of-the-art of mycotoxin MS-based analytical methods for multiclass, multianalyte determination in all the matrices in which they appear. A chapter is devoted to the history of the long-standing coexistence and interaction among humans, domestic animals and mycotoxicosis, and the history of the discovery of mycotoxins. Quality assurance, although this topic relates to analytical chemistry in general, has been also examined for mycotoxin analysis as a preliminary to the systematic literature excursus. Sample handling is a crucial step to devise a multiclass analytical method; so when possible, it has been treated separately for a better comparison before tackling the instrumental part of the whole analytical method. This structure has resulted sometimes in unavoidable redundancies, because it was also important to underline the interconnection. Most reviews do not deal with all the possible mycotoxin sources, including the environmental ones. The focus of this review is the analytical methods based on MS for multimycotoxin class determination. Because the final purpose to devise multimycotoxin analysis should be the assessment of the danger to health of exposition to multitoxicants of natural origin (and possibly also the interaction with anthropogenic contaminants), therefore also the analytical methods for environmental relevant mycotoxins have been thoroughly reviewed. Finally, because the best way to shed light on actual risk assessment could be the individuation of exposure biomarkers, the review covers also the scarce literature on biological fluids. PMID- 22065562 TI - The nuclear proteome of the green alga Chlamydomonas reinhardtii. AB - Nuclear proteins play a central role in regulating gene expression. Their identification is important for understanding how the nuclear repertoire changes over time under different conditions. Nuclear proteins are often underrepresented in proteomic studies due to the frequently low abundance of proteins involved in regulatory processes. So far, only few studies describing the nuclear proteome of plant species have been published. Recently, the genome sequence of the unicellular green alga Chlamydomonas reinhardtii has been obtained and annotated, allowing the development of further detailed studies for this organism. However, a detailed description of its nuclear proteome has not been reported so far. Here, we present an analysis of the nuclear proteome of the sequenced Chlamydomonas strain cc503. Using LC-MS/MS, we identified 672 proteins from nuclei isolates with a maximum 1% peptide spectrum false discovery rate. Besides well-known proteins (e.g. histones), transcription factors and other transcriptional regulators (e.g. tubby and HMG) were identified. The presence of protein motifs in nuclear proteins was investigated by computational tools, and specific over-represented protein motifs were identified. This study provides new insights into the complexity of the nuclear environment and reveals novel putative protein targets for further studies of nuclear mechanisms. PMID- 22065563 TI - Fabrication of protein micropatterns using a functional substrate with convertible protein-adsorption surface properties. AB - A functional substrate capable of regulating protein adsorption was prepared using a crosslinked albumin (cl-albumin) film for use in the fabrication of protein micropatterns. The adsorption of proteins with different characteristics onto cl-albumin film, including serum proteins, serum albumin, and lysozyme, was investigated using a quartz crystal microbalance. The results showed that surfaces coated with cl-albumin film are highly resistant to protein adsorption, regardless of protein charge and rigidity. In addition, this adsorption resistance property can be easily converted to promote protein adsorption by exposing the cl-albumin film to a charged polymer solution. By combining the convertible surface property of cl-albumin film and inkjet printing techniques, a precise protein micropattern was successfully fabricated on the substrate. Protein adsorption onto the wall surface of microchannels could also be suppressed or promoted by coating the surface with cl-albumin film. This approach will aid in the development of biomaterials carrying protein micropatterns, such as biosensors, biochips, and cellular scaffolds. PMID- 22065564 TI - Virtual reality exposure therapy in anxiety disorders: a quantitative meta analysis. AB - Virtual reality exposure therapy (VRET) is a promising intervention for the treatment of the anxiety disorders. The main objective of this meta-analysis is to compare the efficacy of VRET, used in a behavioral or cognitive-behavioral framework, with that of the classical evidence-based treatments, in anxiety disorders. A comprehensive search of the literature identified 23 studies (n = 608) that were included in the final analysis. The results show that in the case of anxiety disorders, (1) VRET does far better than the waitlist control; (2) the post-treatment results show similar efficacy between the behavioral and the cognitive behavioral interventions incorporating a virtual reality exposure component and the classical evidence-based interventions, with no virtual reality exposure component; (3) VRET has a powerful real-life impact, similar to that of the classical evidence-based treatments; (4) VRET has a good stability of results over time, similar to that of the classical evidence-based treatments; (5) there is a dose-response relationship for VRET; and (6) there is no difference in the dropout rate between the virtual reality exposure and the in vivo exposure. Implications are discussed. PMID- 22065565 TI - Transgenic mice with SCA10 pentanucleotide repeats show motor phenotype and susceptibility to seizure: a toxic RNA gain-of-function model. AB - Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder manifested by ataxia and seizure. SCA10 is caused by a large expansion of an intronic ATTCT pentanucleotide repeat in the ATXN10 gene. We have recently postulated a toxic RNA-mediated gain of function in the pathogenesis of spinal cerebellar ataxia type 10 (SCA10). The spliced intron-9 RNA containing the expanded AUUCU repeat aggregates in SCA10 cells and sequesters hnRNP K. hnRNP K sequestration triggers the translocation of protein kinase Cdelta (PKCdelta) to mitochondria, leading to activation of caspase-3 and apoptosis. To confirm the toxic RNA-mediated gain of function, we generated a new transgenic mouse model in which the expanded pentanucleotide repeats are constructed in the 3'-untranslated region (3'UTR) to ensure transcription without translation of the repeat. We constructed an artificial transgene containing the SCA10 (ATTCT)(500) track within the 3'UTR of the LacZ gene driven by the rat prion promoter (PrP) and used this to generate a new transgenic mouse model for SCA10. We then examined these mice for neurological phenotypes and histopathological, molecular, and cellular changes. The transgenic mice showed irregular gait and increased seizure susceptibility at the age of 6 months, resembling the clinical phenotype of SCA10. The cerebral cortex, hippocampus, and pontine nuclei showed neuronal loss. The brains of these animals also showed molecular and cellular changes similar to those previously found in an SCA10 cell model. Expression of the expanded SCA10 AUUCU repeat within the 3'UTR of a gene results in neuronal loss with associated gait abnormalities and increased seizure susceptibility phenotypes, which resemble those seen in SCA10 patients. Moreover, these results bolster the idea that the SCA10 disease mechanism is mediated by a toxic RNA gain-of-function mutation of the expanded AUUCU repeat. PMID- 22065566 TI - Tetra-kis(picolinato-kappaN,O)zirconium(IV) dihydrate. AB - In the title compound, [Zr(C(6)H(4)NO(2))(4)].2H(2)O, the Zr(IV) atom is located on a crystallographic fourfold rotoinversion axis ([Formula: see text]) and is coordinated by four picolinate anions with Zr-O and Zr-N distances of 2.120 (2) and 2.393 (2) A, respectively. An approximate square-anti-prismatic coordination polyhedron of the N,O-coordination ligand atoms is formed, with a distortion towards dodeca-hedral geometry. The crystal packing is stabilized by inter molecular pi-pi inter-actions between adjacent picolinate rings [centroid centroid distances = 3.271 (1) and 3.640 (2) A], as well as O-H?O hydrogen bonds between the solvent mol-ecules and the coordinated ligands, thereby linking the mol-ecules into a supra-molecular three-dimensional network. PMID- 22065567 TI - (E)-6-Amino-1,3-dimethyl-5-[(pyridin-2-yl-methyl-idene)amino]-pyrimidine 2,4(1H,3H)-dione. AB - In the title compound, C(12)H(13)N(5)O(2), a Schiff-base-derived chelate ligand, the non-aromatic heterocycle and its substituents essentially occupy one common plane (r.m.s. of fitted non-H atoms = 0.0503 A). The N=C bond is E-configured. Intra-cyclic angles in the pyridine moiety cover the range 117.6 (2)-124.1 (2) degrees . Intra- and inter-molecular N-H?N and N-H?O hydrogen bonds are observed in the crystal structure, as are intra- and inter-molecular C-H?O contacts which, in total, connect the mol-ecules into a three-dimensional network. The shortest ring-centroid-to-ring-centroid distance of 3.5831 (14) A is between the two different types of six-membered rings. PMID- 22065568 TI - Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer. AB - Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (p<0.05) in bladder cancer samples compared with control urine samples. The increased abundance found in urine from bladder cancer patients compared with controls was confirmed with Western blot for four selected proteins; fibrinogen beta chain precursor, apolipoprotein E, alpha-1-antitrypsin, and leucine-rich alpha-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen beta chain and alpha-1 antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors. PMID- 22065569 TI - (E)-1-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-3-phenyl-prop-2-en-1-one. AB - The asymmetric unit of the title compound, C(19)H(17)N(3)O, contains two independent mol-ecules. In one mol-ecule, the essentially planar triazole ring [maximum deviation = 0.003 (2) A] forms dihedral angles of 5.57 (12) and 87.51 (12) degrees with the two phenyl rings, while in the other mol-ecule [maximum deviation in triazole ring = 0.001 (2) A] these angles are 1.55 (10) and 82.73 (11) degrees . The dihedral angles between the two phenyl rings in the two mol ecules are 87.77 (13) and 81.22 (11) degrees . In the crystal, the independent mol-ecules are connected via a weak C-H?N hydrogen bond, forming dimers. Further stabilization is provided by weak C-H?pi inter-actions. PMID- 22065570 TI - Genetic drift. The mall test (or fun with a dysmorphologist). PMID- 22065571 TI - Disorder-specific mental health service use for mood and anxiety disorders: associations with age, sex, and psychiatric comorbidity. AB - BACKGROUND: The objectives of this study are to examine the prevalence of disorder-specific mental health service use for mood and anxiety disorders, and relationships between helpseeking and age, sex, and psychiatric comorbidity. METHODS: The authors used Wave 2 data from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), which included 34,653 adults. Cross tabulations provided helpseeking prevalence rates for five anxiety disorders and three mood disorders by age and sex, as well as for individuals with and without comorbid anxiety and mood disorders. Logistic regression analyses explored the likelihood of helpseeking among younger and middle-aged adults in comparison to older adults. RESULTS: The prevalence of helpseeking was highest for panic disorder (45.3%) and dysthymia (44.5%) and lowest for specific phobias (7.8%). For each condition except panic disorder service use was most likely among middle aged adults and especially unlikely among older individuals. Sex differences in treatment seeking favoring women showed only modest variability with age. Finally, the prevalence of helpseeking was generally lower among individuals without comorbid anxiety or mood disorders, and the hill-shaped influence of age on service use was attenuated in this pure group. CONCLUSIONS: The results of this study highlight the highest prevalence of disorder-specific service use among middle-aged adults and women, and among individuals with panic disorder and dysthymia. For purposes of identifying groups who are in need of targeted efforts to increase service use, helpseeking was especially unlikely among people suffering from specific phobia, as well as among men and older adults. PMID- 22065572 TI - Inhibitor of kappaB kinase epsilon (IKK(epsilon)), STAT1, and IFIT2 proteins define novel innate immune effector pathway against West Nile virus infection. AB - West Nile virus is an emerging virus whose virulence is dependent upon viral evasion of IFN and innate immune defenses. The actions of IFN-stimulated genes (ISGs) impart control of virus infection, but the specific ISGs and regulatory pathways that restrict West Nile virus (WNV) are not defined. Here we show that inhibitor of kappaB kinase epsilon (IKKepsilon) phosphorylation of STAT1 at serine 708 (Ser-708) drives IFIT2 expression to mediate anti-WNV effector function of IFN. WNV infection was enhanced in cells from IKKepsilon(-/-) or IFIT2(-/-) mice. In IKKepsilon(-/-) cells, the loss of IFN-induced IFIT2 expression was linked to lack of STAT1 phosphorylation on Ser-708 but not Tyr-701 nor Ser-727. STAT1 Ser-708 phosphorylation occurs independently of IRF-3 but requires signaling through the IFN-alpha/beta receptor as a late event in the IFN induced innate immune response that coincides with IKKepsilon-responsive ISGs expression. Biochemical analyses show that STAT1 tyrosine dephosphorylation and CRM1-mediated STAT1 nuclear-cytoplasmic shuttling are required for STAT1 Ser-708 phosphorylation. When compared with WT mice, WNV-infected IKKepsilon(-/-) mice exhibit enhanced kinetics of virus dissemination and increased pathogenesis concomitant with loss of STAT1 Ser-708 phosphorylation and IFIT2 expression. Our results define an IFN-induced IKKepsilon signaling pathway of specific STAT1 phosphorylation and IFIT2 expression that imparts innate antiviral immunity to restrict WNV infection and control viral pathogenesis. PMID- 22065573 TI - Nuclear factor kappaB subunits RelB and cRel negatively regulate Toll-like receptor 3-mediated beta-interferon production via induction of transcriptional repressor protein YY1. AB - The induction of beta-interferon (IFN-beta) is a key anti-viral response to infection by RNA viruses. Virus-induced expression of IFN-beta requires the co operative action of the transcription factors IRF-3/7, NF-kappaB, and ATF-2/c-Jun on the IFN-beta promoter leading to the orderly recruitment of chromatin remodeling complexes. Although viruses strongly activate NF-kappaB and promote its binding to the IFN-beta promoter, recent studies have indicated that NF kappaB is not essential for virus-induced expression of IFN-beta. Herein, we examined the role of NF-kappaB in regulating IFN-beta expression in response to the viral-sensing Toll-like receptor 3 (TLR3). Intriguingly pharmacological inhibition of the NF-kappaB pathway augments late phase expression of IFN-beta expression in response to TLR3 stimulation. We show that the negative effect of NF-kappaB on IFN-beta expression is dependent on the induction of the transcriptional repressor protein YinYang1. We demonstrate that the TLR3 ligand polyriboinosinic:polyribocytidylic acid (poly(I:C)) induces expression and nuclear translocation of YinYang1 where it interacts with the IFN-beta promoter and inhibits the binding of IRF7 to the latter. Evidence is also presented showing that the NF-kappaB subunits c-Rel and RelB are the likely key drivers of these negative effects on IFN-beta expression. These findings thus highlight for the first time a novel self-regulatory mechanism that is employed by TLR3 to limit the level and duration of IFN-beta expression. PMID- 22065574 TI - Alternative mRNA splicing of corepressors generates variants that play opposing roles in adipocyte differentiation. AB - The SMRT and NCoR corepressors partner with, and help mediate repression by, a wide variety of nuclear receptors and non-receptor transcription factors. Both SMRT and NCoR are expressed by alternative mRNA splicing, resulting in the production of a series of interrelated corepressor variants that differ in their tissue distribution and in their biochemical properties. We report here that different corepressor splice variants can exert opposing transcriptional and biological effects during adipocyte differentiation. Most notably, the NCoRomega splice variant inhibits, whereas the NCoRdelta splice variant promotes, adipogenesis. Furthermore, the ratio of NCoRomega to NCoRdelta decreases during adipogenic differentiation. We propose that this alteration in corepressor splicing helps convert the cellular transcriptional program from one that maintains the pre-adipocyte in an undifferentiated state to a new transcriptional context that promotes differentiation and helps establish the proper physiology of the mature adipocyte. PMID- 22065575 TI - The WD40 repeat protein WDR26 binds Gbetagamma and promotes Gbetagamma-dependent signal transduction and leukocyte migration. AB - The Gbetagamma subunits of heterotrimeric G proteins transmit signals to control many cellular processes, including leukocyte migration. Gbetagamma signaling may regulate and be regulated by numerous signaling partners. Here, we reveal that WDR26, a member of the WD40 repeat protein family, directly bound free Gbetagamma in vitro, and formed a complex with endogenous Gbetagamma in Jurkat T cells stimulated by the chemokine SDF1alpha. Suppression of WDR26 by siRNAs selectively inhibited Gbetagamma-dependent phospholipase Cbeta and PI3K activation, and attenuated chemotaxis in Jurkat T cells and differentiated HL60 cells in vitro and Jurkat T cell homing to lymphoid tissues in scid mice. Similarly, disruption of the WDR26/Gbetagamma interaction via expression of a WDR26 deletion mutant impaired Gbetagamma signaling and Jurkat T cell migration, indicating that the function of WDR26 depends on its binding to Gbetagamma. Additional data show that WDR26 also controlled RACK1, a negative regulator, in binding Gbetagamma and inhibiting leukocyte migration. Collectively, these experiments identify WDR26 as a novel Gbetagamma-binding protein that is required for the efficacy of Gbetagamma signaling and leukocyte migration. PMID- 22065576 TI - Signal-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate without activation of phospholipase C: implications on gating of Drosophila TRPL (transient receptor potential-like) channel. AB - In Drosophila, a phospholipase C (PLC)-mediated signaling cascade, couples photo excitation of rhodopsin to the opening of the transient receptor potential (TRP) and TRP-like (TRPL) channels. A lipid product of PLC, diacylglycerol (DAG), and its metabolites, polyunsaturated fatty acids (PUFAs) may function as second messengers of channel activation. However, how can one separate between the increase in putative second messengers, change in pH, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) depletion when exploring the TRPL gating mechanism? To answer this question we co-expressed the TRPL channels together with the muscarinic (M1) receptor, enabling the openings of TRPL channels via G protein activation of PLC. To dissect PLC activation of TRPL into its molecular components, we used a powerful method that reduced plasma membrane-associated PI(4,5)P(2) in HEK cells within seconds without activating PLC. Upon the addition of a dimerizing drug, PI(4,5)P(2) was selectively hydrolyzed in the cell membrane without producing DAG, inositol trisphosphate, or calcium signals. We show that PI(4,5)P(2) is not an inhibitor of TRPL channel activation. PI(4,5)P(2) hydrolysis combined with either acidification or application of DAG analogs failed to activate the channels, whereas PUFA did activate the channels. Moreover, a reduction in PI(4,5)P(2) levels or inhibition of DAG lipase during PLC activity suppressed the PLC-activated TRPL current. This suggests that PI(4,5)P(2) is a crucial substrate for PLC-mediated activation of the channels, whereas PUFA may function as the channel activator. Together, this study defines a narrow range of possible mechanisms for TRPL gating. PMID- 22065577 TI - Subunit and domain requirements for adenylate-mediated protection of Snf1 kinase activation loop from dephosphorylation. AB - Members of the AMP-activated protein kinase (AMPK) family are activated by phosphorylation at a conserved threonine residue in the activation loop of the kinase domain. Mammalian AMPK adopts a phosphatase-resistant conformation that is stabilized by binding low energy adenylate molecules. Similarly, binding of ADP to the Snf1 complex, yeast AMPK, protects the kinase from dephosphorylation. Here, we determined the nucleotide specificity of the ligand-mediated protection from dephosphorylation and demonstrate the subunit and domain requirements for this reaction. Protection from dephosphorylation was highly specific for adenine nucleotides, with ADP being the most effective ligand for mediating protection. The full-length alpha subunit (Snf1) was not competent for ADP-mediated protection, confirming the requirement for the regulatory beta and gamma subunits. However, Snf1 heterotrimeric complexes that lacked either the glycogen binding domain of Gal83 or the linker region of the alpha subunit were competent for ADP-mediated protection. In contrast, adenylate-mediated protection of recombinant human AMPK was abolished when a portion of the linker region containing the alpha-hook domain was deleted. Therefore, the exact means by which the different adenylate nucleotides are distinguished by the Snf1 enzyme may differ compared with its mammalian ortholog. PMID- 22065578 TI - Natural diterpenoid compound elevates expression of Bim protein, which interacts with antiapoptotic protein Bcl-2, converting it to proapoptotic Bax-like molecule. AB - Overwhelming evidence indicates that Bax and Bak are indispensable for mediating cytochrome c release from mitochondria during apoptosis. Here we report a Bax/Bak independent mechanism of cytochrome c release and apoptosis. We identified a natural diterpenoid compound that induced apoptosis in bax/bak double knock-out murine embryonic fibroblasts and substantially reduced the tumor growth from these cells implanted in mice. Treatment with the compound significantly increased expression of Bim, which migrated to mitochondria, altering the conformation of and forming oligomers with resident Bcl-2 to induce cytochrome c release and caspase activation. Importantly, purified Bim and Bcl-2 proteins cooperated to permeabilize a model mitochondrial outer membrane; this was accompanied by oligomerization of these proteins and deep embedding of Bcl-2 in the membrane. Therefore, the diterpenoid compound induces a structural and functional conversion of Bcl-2 through Bim to permeabilize the mitochondrial outer membrane, thereby inducing apoptosis independently of Bax and Bak. Because Bcl-2 family proteins play important roles in cancer development and relapse, this novel cell death mechanism can be explored for developing more effective anticancer therapeutics. PMID- 22065579 TI - Formation of ternary complex of human biliverdin reductase-protein kinase Cdelta ERK2 protein is essential for ERK2-mediated activation of Elk1 protein, nuclear factor-kappaB, and inducible nitric-oxidase synthase (iNOS). AB - Growth factors, insulin, oxidative stress, and cytokines activate ERK1/2 by PKCdelta and MEK1/2. Human biliverdin reductase (hBVR), a Ser/Thr/Tyr kinase and intracellular scaffold/bridge/anchor, is a nuclear transporter of MEK1/2 stimulated ERK1/2 (Lerner-Marmarosh, N., Miralem, T., Gibbs, P. E., and Maines, M. D. (2008) Proc. Natl. Acad. Sci. U.S.A. 105, 6870-6875). hBVR, PKCdelta, and MEK1/2 overlap in their tissue expression profile and type of activators. Presently, we report on formation of an hBVR-PKCdelta-ERK2 ternary complex that is essential for ERK2 signal transduction and activation of genes linked to cell proliferation and cancer. MEK1/2 and the protein phosphatase PP2A were also present in the complex. When cells were stimulated with insulin-like growth factor-1 (IGF-1), an increased interaction between hBVR and PKCdelta was detected by FRET-fluorescence lifetime imaging microscopy. hBVR and ERK2 were phosphorylated by PKCdelta; however, the PKC was not a substrate for either ERK2 or hBVR. IGF-1 and phorbol ester increased hBVR/PKCdelta binding; hBVR was required for the activation of PKCdelta and its interaction with ERK2. The C terminal phenylalanine residues of PKCdelta (Phe(660), Phe(663), and Phe(665)) were necessary for binding to ERK2 but not for hBVR binding. Formation of the hBVR-PKCdelta-ERK2 complex required the hBVR docking site for ERK, FXFP (DEF, C box) and D(delta)-box (ILXXLXL) motifs. The hBVR-based peptide KKRILHCLGLA inhibited PKC activation and PKCdelta/ERK2 interaction. Phorbol ester- and TNF alpha-dependent activation of the ERK-regulated transcription factors Elk1 and NF kappaB and expression of the iNOS gene were suppressed by hBVR siRNA; those activities were rescued by hBVR. The findings reveal the direct input of hBVR in PKCdelta/ERK signaling and identify hBVR-based peptide regulators of ERK-mediated gene activation. PMID- 22065580 TI - Crystal structure and RNA binding properties of the RNA recognition motif (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an enzyme catalyzing tRNA hypermodification. AB - Humans express nine paralogs of the bacterial DNA repair enzyme AlkB, an iron/2 oxoglutarate-dependent dioxygenase that reverses alkylation damage to nucleobases. The biochemical and physiological roles of these paralogs remain largely uncharacterized, hampering insight into the evolutionary expansion of the AlkB family. However, AlkB homolog 8 (ABH8), which contains RNA recognition motif (RRM) and methyltransferase domains flanking its AlkB domain, recently was demonstrated to hypermodify the anticodon loops in some tRNAs. To deepen understanding of this activity, we performed physiological and biophysical studies of ABH8. Using GFP fusions, we demonstrate that expression of the Caenorhabditis elegans ABH8 ortholog is widespread in larvae but restricted to a small number of neurons in adults, suggesting that its function becomes more specialized during development. In vitro RNA binding studies on several human ABH8 constructs indicate that binding affinity is enhanced by a basic alpha-helix at the N terminus of the RRM domain. The 3.0-A-resolution crystal structure of a construct comprising the RRM and AlkB domains shows disordered loops flanking the active site in the AlkB domain and a unique structural Zn(II)-binding site at its C terminus. Although the catalytic iron center is exposed to solvent, the 2 oxoglutarate co-substrate likely adopts an inactive conformation in the absence of tRNA substrate, which probably inhibits uncoupled free radical generation. A conformational change in the active site coupled to a disorder-to-order transition in the flanking protein segments likely controls ABH8 catalytic activity and tRNA binding specificity. These results provide insight into the functional and structural adaptations underlying evolutionary diversification of AlkB domains. PMID- 22065581 TI - Human mutation within Per-Arnt-Sim (PAS) domain-containing protein kinase (PASK) causes basal insulin hypersecretion. AB - PAS kinase (PASK) is a glucose-regulated protein kinase involved in the control of pancreatic islet hormone release and insulin sensitivity. We aimed here to identify mutations in the PASK gene that may be associated with young-onset diabetes in humans. We screened 18 diabetic probands with unelucidated maturity onset diabetes of the young (MODY). We identified two rare nonsynonymous mutations in the PASK gene (p.L1051V and p.G1117E), each of which was found in a single MODY family. Wild type or mutant PASKs were expressed in HEK 293 cells. Kinase activity of the affinity-purified proteins was assayed as autophosphorylation at amino acid Thr307 or against an Ugp1p-derived peptide. Whereas the PASK p.G1117E mutant displayed a ~25% increase with respect to wild type PASK in the extent of autophosphorylation, and a ~2-fold increase in kinase activity toward exogenous substrates, the activity of the p.L1051V mutant was unchanged. Amino acid Gly1117 is located in an alpha helical region opposing the active site of PASK and may elicit either: (a) a conformational change that increases catalytic efficiency or (b) a diminished inhibitory interaction with the PAS domain. Mouse islets were therefore infected with adenoviruses expressing wild type or mutant PASK and the regulation of insulin secretion was examined. PASK p.G1117E-infected islets displayed a 4-fold decrease in glucose-stimulated (16.7 versus 3 mM) insulin secretion, chiefly reflecting a 4.5-fold increase in insulin release at low glucose. In summary, we have characterized a rare mutation (p.G1117E) in the PASK gene from a young-onset diabetes family, which modulates glucose-stimulated insulin secretion. PMID- 22065582 TI - Exogenous ceramide-1-phosphate reduces lipopolysaccharide (LPS)-mediated cytokine expression. AB - Toll-like receptor 4 (TLR4) is a component of the innate immune system that recognizes a diverse group of molecular structures, such as lipopolysaccharide (LPS) from Gram-negative bacteria. TLR4 signaling ultimately leads to activation of the transcription factor, nuclear factor kappaB (NF-kappaB), and the production of cytokines. Ceramide is a bioactive sphingolipid that has been suggested to regulate TLR4-induced NF-kappaB signaling, although reports on the role of ceramide in TLR4 activation conflict. We investigated the possibility that ceramide metabolites, such as ceramide-1-phosphate (C-1-P), may explain these discrepancies. We now report that exogenous C-1-P, but not ceramide, reduces NF-kappaB-mediated gene transcription in HEK 293 cells stably transfected with human TLR4, CD14, and MD-2. We demonstrate that inhibition of NF-kappaB by exogenous C-1-P is dose-dependent and specific to TLR4 in a reporter assay. We further demonstrate a requirement for both the phosphate moiety and the sphingoid backbone to inhibit LPS-activated NF-kappaB transcription. Specifically, C-1-P prevents the degradation of IkappaB, the phosphorylation of the p65 subunit of NF kappaB, and LPS-stimulated MAPK activation. The functional consequence of C-1-P inhibition of NF-kappaB is a reduction in LPS-mediated cytokine release from HEK 293 TLR4-expressing cells and human peripheral blood mononuclear cells. Taken together, these data demonstrate that C-1-P may function as an anti-inflammatory lipid mediator of immune response. PMID- 22065583 TI - Global expression analysis identified a preferentially nerve growth factor induced transcriptional program regulated by sustained mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) and AP-1 protein activation during PC12 cell differentiation. AB - Neuronal differentiation of PC12 cells in response to NGF is a prototypical model in which signal duration determines a biological response. Sustained ERK activity induced by NGF, as compared with transient activity induced by EGF, is critical to the differentiation of these cells. To characterize the transcriptional program activated preferentially by NGF, we compared global gene expression profiles between cells treated with NGF and EGF for 2-4 h, when sustained ERK signaling in response to NGF is most distinct from the transient signal elicited by EGF. This analysis identified 69 genes that were preferentially up-regulated in response to NGF. As expected, up-regulation of these genes was mediated by sustained ERK signaling. In addition, they were up-regulated in response to other neuritogenic treatments (pituitary adenylate cyclase-activating polypeptide and 12-O-tetradecanoylphorbol-13-acetate plus dbcAMP) and were enriched for genes related to neuronal differentiation/function. Computational analysis and chromatin immunoprecipitation identified binding of CREB and AP-1 family members (Fos, FosB, Fra1, JunB, JunD) upstream of >30 and 50%, respectively, of the preferentially NGF-induced genes. Expression of several AP-1 family members was induced by both EGF and NGF, but their induction was more robust and sustained in response to NGF. The binding of Fos family members to their target genes was similarly sustained in response to NGF and was reduced upon MEK inhibition, suggesting that AP-1 contributes significantly to the NGF transcriptional program. Interestingly, Fra1 as well as two other NGF-induced AP-1 targets (HB EGF and miR-21) function in positive feedback loops that may contribute to sustained AP-1 activity. PMID- 22065584 TI - Translational repression of the disintegrin and metalloprotease ADAM10 by a stable G-quadruplex secondary structure in its 5'-untranslated region. AB - Anti-amyloidogenic processing of the amyloid precursor protein APP by alpha secretase prevents formation of the amyloid-beta peptide, which accumulates in senile plaques of Alzheimer disease patients. alpha-Secretase belongs to the family of a disintegrin and metalloproteases (ADAMs), and ADAM10 is the primary candidate for this anti-amyloidogenic activity. We recently demonstrated that ADAM10 translation is repressed by its 5'-UTR and that in particular the first half of ADAM10 5'-UTR is responsible for translational repression. Here, we asked whether specific sequence motifs exist in the ADAM10 5'-UTR that are able to form complex secondary structures and thus potentially inhibit ADAM10 translation. Using circular dichroism spectroscopy, we demonstrate that a G-rich region between nucleotides 66 and 94 of the ADAM10 5'-UTR forms a highly stable, intramolecular, parallel G-quadruplex secondary structure under physiological conditions. Mutation of guanines in this sequence abrogates the formation of the G-quadruplex structure. Although the G-quadruplex structure efficiently inhibits translation of a luciferase reporter in in vitro translation assays and in living cells, inhibition of G-quadruplex formation fails to do so. Moreover, expression of ADAM10 was similarly repressed by the G-quadruplex. Mutation of the G quadruplex motif results in a significant increase of ADAM10 levels and consequently APPsalpha secretion. Thus, we identified a critical RNA secondary structure within the 5'-UTR, which contributes to the translational repression of ADAM10. PMID- 22065585 TI - Conserved structural mechanisms for autoinhibition in IpaH ubiquitin ligases. AB - The IpaH family of novel E3 ligase (NEL) enzymes occur in a variety of pathogenic and commensal bacteria that interact with eukaryotic hosts. We demonstrate that the leucine-rich repeat (LRR) substrate recognition domains of different IpaH enzymes autoinhibit the enzymatic activity of the adjacent catalytic novel E3 ligase domain by two distinct but conserved structural mechanisms. Autoinhibition is required for the in vivo biological activity of two IpaH enzymes in a eukaryotic model system. Autoinhibition was retro-engineered into a constitutively active IpaH enzyme from Yersinia pestis by introduction of single site substitutions, thereby demonstrating the conservation of autoregulatory infrastructure across the IpaH enzyme family. PMID- 22065586 TI - Oncogenic Ras and B-Raf proteins positively regulate death receptor 5 expression through co-activation of ERK and JNK signaling. AB - Oncogenic mutations of ras and B-raf frequently occur in many cancer types and are critical for cell transformation and tumorigenesis. Death receptor 5 (DR5) is a cell surface pro-apoptotic death receptor for tumor necrosis factor-related apoptosis-inducing ligand and has been targeted in cancer therapy. The current study has demonstrated induction of DR5 expression by the oncogenic proteins Ras and B-Raf and revealed the underlying mechanisms. We demonstrated that both Ras and B-Raf induce DR5 expression by enforced expression of oncogenic Ras (e.g. H Ras12V or K-Ras12V) or B-Raf (i.e. V600E) in cells and by analyzing gene expression array data generated from cancer cell lines and from human cancer tissues. This finding is further supported by our results that knockdown of endogenous K-Ras or B-Raf (V600E) reduced the expression of DR5. Importantly, we have elucidated that Ras induces DR5 expression through co-activation of ERK/RSK and JNK signaling pathways and subsequent cooperative effects among the transcriptional factors CHOP, Elk1, and c-Jun to enhance DR5 gene transcription. Moreover, we found that the majority of cancer cell lines highly sensitive to the DR5 agonistic antibody AMG655 have either Ras or B-Raf mutations. Our findings warrant further study on the biology of DR5 regulation by Ras and B-Raf, which may provide new insight into the biology of Ras and B-Raf, and on the potential impact of Ras or B-Raf mutations on the outcome of DR5-targeted cancer therapy. PMID- 22065587 TI - 3-Formylchromone interacts with cysteine 38 in p65 protein and with cysteine 179 in IkappaBalpha kinase, leading to down-regulation of nuclear factor-kappaB (NF kappaB)-regulated gene products and sensitization of tumor cells. AB - 3-Formylchromone (3-FC) has been associated with anticancer potential through a mechanism yet to be elucidated. Because of the critical role of NF-kappaB in tumorigenesis, we investigated the effect of this agent on the NF-kappaB activation pathway. Whether activated by inflammatory agents (such as TNF-alpha and endotoxin) or tumor promoters (such as phorbol ester and okadaic acid), 3-FC suppressed NF-kappaB activation. It also inhibited constitutive NF-kappaB expressed by most tumor cells. This activity correlated with sequential inhibition of IkappaBalpha kinase (IKK) activation, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and reporter gene expression. We found that 3-FC inhibited the direct binding of p65 to DNA, and this binding was reversed by a reducing agent, thus suggesting a role for the cysteine residue. Furthermore, mutation of Cys38 to Ser in p65 abolished this effect of the chromone. This result was confirmed by a docking study. 3-FC also inhibited IKK activation directly, and the reducing agent reversed this inhibition. Furthermore, mutation of Cys179 to Ala in IKK abolished the effect of the chromone. Suppression of NF-kappaB activation led to inhibition of anti apoptotic (Bcl-2, Bcl-xL, survivin, and cIAP-1), proliferative (cyclin D1 and COX 2), invasive (MMP-9 and ICAM-1), and angiogenic (VEGF) gene products and sensitization of tumor cells to cytokines. Thus, this study shows that modification of cysteine residues in IKK and p65 by 3-FC leads to inhibition of the NF-kappaB activation pathway, suppression of anti-apoptotic gene products, and potentiation of apoptosis in tumor cells. PMID- 22065588 TI - Crystal structures of the laminarinase catalytic domain from Thermotoga maritima MSB8 in complex with inhibitors: essential residues for beta-1,3- and beta-1,4 glucan selection. AB - Laminarinases hydrolyzing the beta-1,3-linkage of glucans play essential roles in microbial saccharide degradation. Here we report the crystal structures at 1.65 1.82 A resolution of the catalytic domain of laminarinase from the thermophile Thermotoga maritima with various space groups in the ligand-free form or in the presence of inhibitors gluconolactone and cetyltrimethylammonium. Ligands were bound at the cleft of the active site near an enclosure formed by Trp-232 and a flexible GASIG loop. A closed configuration at the active site cleft was observed in some molecules. The loop flexibility in the enzyme may contribute to the regulation of endo- or exo-activity of the enzyme and a preference to release laminaritrioses in long chain carbohydrate hydrolysis. Glu-137 and Glu-132 are proposed to serve as the proton donor and nucleophile, respectively, in the retaining catalysis of hydrolyzation. Calcium ions in the crystallization media are found to accelerate crystal growth. Comparison of laminarinase and endoglucanase structures revealed the subtle difference of key residues in the active site for the selection of beta-1,3-glucan and beta-1,4-glucan substrates, respectively. Arg-85 may be pivotal to beta-1,3-glucan substrate selection. The similarity of the structures between the laminarinase catalytic domain and its carbohydrate-binding modules may have evolutionary relevance because of the similarities in their folds. PMID- 22065589 TI - Polypeptide modulators of caspase recruitment domain (CARD)-CARD-mediated protein protein interactions. AB - The caspase recruitment domain (CARD) is present in a large number of proteins. Initially, the CARD was recognized as part of the caspase activation machinery. CARD-CARD interactions play a role in apoptosis and are responsible for the Apaf 1-mediated activation of procaspase-9 in the apoptosome. CARD-containing proteins mediate the inflammasome-dependent activation of proinflammatory caspase-1. More recently, new roles for CARD-containing proteins have been reported in signaling pathways associated with immune responses. The functional role of CARD-containing proteins and CARDs in coordinating apoptosis and inflammatory and immune responses is not completely understood. We have explored the putative cross-talk between apoptosis and inflammation by analyzing the modulatory activity on both the Apaf-1/procaspase-9 interaction and the inflammasome-mediated procaspase-1 activation of CARD-derived polypeptides. To this end, we analyzed the activity of individual recombinant CARDs, rationally designed CARD-derived peptides, and peptides derived from phage display. PMID- 22065590 TI - Critical role of calpain in axonal damage-induced retinal ganglion cell death. AB - Calpain, an intracellular cysteine protease, has been widely reported to be involved in neuronal cell death. The purpose of this study is to investigate the role of calpain activation in axonal damage-induced retinal ganglion cell (RGC) death. Twelve-week-old male calpstatin (an endogenous calpain inhibitor) knockout mice (CAST KO) and wild-type (WT) mice were used in this study. Axonal damage was induced by optic nerve crush (NC) or tubulin destruction induced by leaving a gelatin sponge soaked with vinblastine (VB), a microtubule disassembly chemical, around the optic nerve. Calpain activation was assessed by immunoblot analysis, which indirectly quantified the cleaved alpha-fodrin, a substrate of calpain. RGCs were retrogradely labeled by injecting a fluorescent tracer, Fluoro-Gold (FG), and the retinas were harvested and flat-mounted retinas prepared. The densities of FG-labeled RGCs harvested from the WT and CAST KO groups were assessed and compared. Additionally, a calpain inhibitor (SNJ-1945, 100 mg/kg/day) was administered orally, and the density of surviving RGCs was compared with that of the vehicle control group. The mean density of surviving RGCs in the CAST KO group was significantly lower than that observed in the WT group, both in NC and in VB. The mean density of surviving RGCs in the SNJ-1945 treated group was significantly higher than that of the control group. The calpain inhibitor SNJ-1945 has a neuroprotective effect against axonal damage induced RGC death. This pathway may be an important therapeutic target for preventing this axonal damage-induced RGC death, including glaucoma and diabetic optic neuropathy and other CNS diseases that share a common etiology. PMID- 22065591 TI - 14-3-3epsilon marks the amyloid-stimulated microglia long-term activation. AB - Microglia-mediated inflammation in the central nervous system is a hallmark of the pathogenesis of several neurodegenerative diseases including Alzheimer's disease. Microglial cells activation follows the deposition of amyloid beta fibrils and it is generally considered a triggering factor in the early steps of the onset of Alzheimer's disease. Although the initial engagement of microglia seems to play a neuroprotective role, many lines of evidence indicate that a persistent activation with the production of proinflammatory molecules contributes to dismantle neuronal activity and to induce neuronal loss occurring in neurodegenerative diseases. To date, limited proteomic data are available on activated microglial cells in response to extracellular amyloidogenic peptides. In this study, murine microglial cells have been employed to investigate the effects of amyloid beta peptides in triggering microglial activation. The response was monitored at the proteome level through a two-dimensional gel electrophoresis-based approach. Results show only a limited number of differentially expressed proteins, among these a more acidic species of the cytosolic actin, and the 14-3-3epsilon protein, found significantly upregulated in Abeta-activated cells. 14-3-3epsilon belongs to a regulatory protein family involved in important cellular processes, including those leading to neurodegenerative diseases, and thus its increased expression suggests a role of this protein in tuning microglia activation. PMID- 22065592 TI - Two large-scale surveys on community attitudes toward an opt-out biobank. AB - Although US research regulations allow for de-identified biorepositories to be developed without formal informed consent from the patients whose samples are included, it is unknown whether this model will be well-received by community members. Based on early evidence that such a biobank could be successful if patients who object have the opportunity to opt-out, Vanderbilt University developed a biorepository named BioVU that follows this model. This study reports the findings from two large-scale surveys among communities important to this biorepository. In the first, a population-based phone survey of Nashville residents, we found that approval for BioVU is high (93.9%) and that this approval is similar among all population groups. A hypothetical biobank that does not obtain some form of written permission is much less well received. In the second, an online survey of Vanderbilt University faculty and staff, we found a higher level of support for BioVU (94.5%) among faculty and staff working throughout the university. In this survey, employees least likely to approve of BioVU are those employees who prefer not to receive medical care at Vanderbilt University. These surveys demonstrate the highest level of approval for a genomic biobank ever reported in the literature, even among groups traditionally cautious about such research. This high level of approval may reflect increasing comfort with genomic research over time combined with the effect that trust in a specific institution can have on approval for an operating biobank compared with approval of a hypothetical biobank. PMID- 22065593 TI - Attachment and alliance in the treatment of depressed, sexually abused women. AB - BACKGROUND: Depression among women with sexual abuse histories is less treatment responsive than in general adult samples. One contributor to poorer treatment outcomes may be abused women's difficulties in forming and maintaining secure relationships, as reflected in insecure attachment styles, which could also impede the development of a positive therapeutic alliance. The current study examines how attachment orientation (i.e. anxiety and avoidance) and development of the working alliance are associated with treatment outcomes among depressed women with histories of childhood sexual abuse. METHOD: Seventy women seeking treatment in a community mental health center who had Major Depressive Disorder and a childhood sexual abuse history were randomized to Interpersonal Psychotherapy or treatment as usual. RESULTS: Greater attachment avoidance and weaker working alliance were each related to worse depression symptom outcomes; these effects were independent of the presence of comorbid Borderline Personality Disorder and Post-Traumatic Stress Disorder. The effect of avoidant attachment on outcomes was not mediated by the working alliance. Further, working alliance had a stronger effect on depression outcomes in the Interpersonal Psychotherapy group. CONCLUSION: Understanding the influence of attachment style and the working alliance on treatment outcomes can inform efforts to improve the treatments for depressed women with a history of childhood sexual abuse. PMID- 22065594 TI - Immunoglobulin D amyloidosis: a distinct entity. AB - IgD monoclonal gammopathies are uncommon. They are seen rarely as a monoclonal gammopathy of undetermined significance and are present in 1%-2% of patients with multiple myeloma. In light-chain amyloidosis, IgD monoclonal proteins are found in ap-proximately 1% of patients. When an IgD monoclonal protein is found, amyloidosis is often omitted from the differential diagnosis. In the present study, we reviewed the natural history of IgD-associated amyloidosis among 53 patients seen over 41 years. The distribution of clinical syndromes suggests that these patients have a lower frequency of renal and cardiac involvement. The overall survival of these patients does not appear to be different from that of patients who have light-chain amyloidosis associated with another monoclonal protein. PMID- 22065595 TI - The relationship between tissue factor and cancer progression: insights from bench and bedside. AB - It is now widely recognized that a strong correlation exists between cancer and aberrant hemostasis. Patients with various types of cancers, including pancreatic, colorectal, and gastric cancer, often develop thrombosis, a phenomenon commonly referred to as Trousseau syndrome. Reciprocally, components from the coagulation cascade also influence cancer progression. The primary initiator of coagulation, the transmembrane receptor tissue factor (TF), has gained considerable attention as a determinant of tumor progression. On complex formation with its ligand, coagulation factor VIIa, TF influences protease activated receptor-dependent tumor cell behavior, and regulates integrin function, which facilitate tumor angiogenesis both in vitro and in mouse models. Furthermore, evidence exists that an alternatively spliced isoform of TF also affects tumor growth and tumor angiogenesis. In patient material, TF expression and TF cytoplasmic domain phosphorylation correlate with disease outcome in many, but not in all, cancer subtypes, suggesting that TF-dependent signal transduction events are a potential target for therapeutic intervention in selected types of cancer. In this review, we summarize our current understanding of the role of TF in tumor growth and metastasis, and speculate on anticancer therapy by targeting TF. PMID- 22065596 TI - Defects in Glanzmann thrombasthenia and LAD-III (LAD-1/v) syndrome: the role of integrin beta1 and beta3 in platelet adhesion to collagen. AB - Patients with Glanzmann thrombasthenia or Leukocyte Adhesion Deficiency-III syndrome (LAD-III or LAD-1/variant) present with increased bleeding tendency because of the lack or dysfunction of the fibrinogen receptor GPIIb/IIIa (integrin alphaIIbbeta3), respectively. Although the bleeding disorder is more severe in LAD-III patients, classic aggregometry or perfusion of Glanzmann or LAD III platelets over collagen-coated slides under physiologic shear rate does not discriminate between these 2 conditions. However, in a novel flow cytometry-based aggregation assay, Glanzmann platelets were still capable of forming small aggregates upon collagen stimulation, whereas LAD-III platelets were not. These aggregates required functional GPIa/IIa (integrin alpha2beta1) instead of integrin alphaIIbbeta3, thus explaining the clinically more severe bleeding manifestations in LAD-III patients, in which all platelet integrins are functionally defective. These findings provide genetic evidence for the differential requirements of platelet integrins in thrombus formation and demonstrate that correct integrin function assessment can be achieved with a combination of diagnostic methods. PMID- 22065597 TI - The cell cycle regulator CDC25A is a target for JAK2V617F oncogene. AB - The JAK2(V617F) mutation is present in the majority of patients with polycythemia vera and one-half of those with essential thrombocythemia and primary myelofibrosis. JAK2(V617F) is a gain-of-function mutation resulting in constitutive JAK2 signaling involved in the pathogenesis of these diseases. JAK2(V617F) has been shown to promote S-phase entry. Here, we demonstrate that the CDC25A phosphatase, a key regulator of the G1/S cell-cycle transition, is constitutively overexpressed in JAK2(V617F)-positive cell lines, JAK2-mutated patient CD36(+) progenitors, and in vitro-differentiated proerythroblasts. Accordingly, CDC25A is overexpressed in BM and spleen of Jak2(V617F) knock-in mice compared with wild-type littermates. By using murine FDC-P1-EPOR and human HEL and SET-2 cell lines, we found that JAK2(V617F)-induced CDC25A up-regulation was caused neither by increased CDC25A transcription or stability nor by the involvement of its upstream regulators Akt and MAPK. Instead, our results suggest that CDC25A is regulated at the translational level through STAT5 and the translational initiation factor eIF2alpha. CDC25A inhibition reduces the clonogenic and proliferative potential of JAK2(V617F)-expressing cell lines and erythroid progenitors while moderately affecting normal erythroid differentiation. These results suggest that CDC25A deregulation may be involved in hematopoietic cells expansion in JAK2(V617F) patients, making this protein an attracting potential therapeutic target. PMID- 22065598 TI - The PI3K/PKB signaling module as key regulator of hematopoiesis: implications for therapeutic strategies in leukemia. AB - An important mediator of cytokine signaling implicated in regulation of hematopoiesis is the PI3K/protein kinase B (PKB/c-Akt) signaling module. Constitutive activation of this signaling module has been observed in a large group of leukemias. Because activation of this signaling pathway has been demonstrated to be sufficient to induce hematologic malignancies and is thought to correlate with poor prognosis and enhanced drug resistance, it is considered to be a promising target for therapy. A high number of pharmacologic inhibitors directed against either individual or multiple components of this pathway have already been developed to improve therapy. In this review, the safety and efficacy of both single and dual-specificity inhibitors will be discussed as well as the potential of combination therapy with either inhibitors directed against other signal transduction molecules or classic chemotherapy. PMID- 22065599 TI - Tcl1 interacts with Atm and enhances NF-kappaB activation in hematologic malignancies. AB - The T-cell leukemia/lymphoma 1 (TCL1) oncogene is a target of chromosomal translocations and inversions at 14q31.2, and its rearrangement in T cells causes T-cell prolymphocytic leukemias. TCL1 dysregulation in B cells is responsible for the development of an aggressive form of chronic lymphocytic leukemia (CLL), the most common human leukemia. We have investigated the mechanisms underlying the oncogenic functions of Tcl1 protein using a mass spectrometry approach and have identified Atm (ataxia-telangiectasia mutated) as a candidate Tcl1-interacting protein. The Tcl1-Atm complex formation was validated by coimmunoprecipitation experiments. Importantly, we show that the association of Atm with Tcl1 leads to enhanced IkappaBalpha phosphorylation and ubiquitination and subsequent activation of the NF-kappaB pathway. Our findings reveal functional cross-talk between Atm and Tcl1 and provide evidence for a novel pathway that could be targeted in leukemias and lymphomas. PMID- 22065600 TI - (4-Bromo-2-{[2-(morpholin-4-yl)ethyl-imino]-meth-yl}phenolato)dioxido vanadium(V). AB - In the title mononuclear dioxidovanadium(V) complex, [V(C(13)H(16)BrN(2)O(2))O(2)], the V(V) atom is five-coordinated by one phenolate O, one imine N and one morpholine N atom of the Schiff base ligand, and by two oxide O atoms, forming a distorted square-pyramidal geometry. In the crystal, weak C-H?O inter-actions and a short Br?Br contact [3.4597 (12) A] are observed. PMID- 22065601 TI - Cellular and molecular effects of resveratrol in health and disease. AB - Resveratrol, a natural polyphenol abundantly found in grape skins and red wine, possesses diverse biochemical and physiological actions, including anti inflammatory, anti-oxidation, anti-proliferation and promotion of differentiation, and chemopreventive effects. Recently, it is attracting increased attention due to its health benefits, especially in common age-related diseases such as cardiovascular disease, cancer, type 2 diabetes, and neurological conditions. In this review, we discuss the latest cellular and molecular findings that account for the beneficial actions of resveratrol. PMID- 22065602 TI - UTP affects the Schwannoma cell line proteome through P2Y receptors leading to cytoskeletal reorganisation. AB - Glial cells in the peripheral nervous system, such as Schwann cells, respond to nucleotides, which play an important role in axonal regeneration and myelination. Metabotropic P2Y receptor agonists are promising therapeutic molecules for peripheral neuropathies. Nevertheless, the proteomic mechanisms involved in nucleotide action on Schwann cells remain unknown. Here, we studied intracellular protein changes in RT4-D6P2T Schwann cells after treatment with nucleotides and Nucleo CMP Forte (CMPF), a nucleotide-based drug. After treatment with CMPF, 2-D DIGE revealed 11 differential gel spots, which were all upregulated. Among these, six different proteins were identified by MS. Some of these proteins are involved in actin remodelling (actin-related protein, Arp3), membrane vesicle transport (Rab GDP dissociation inhibitor beta, Rab GDI), and the endoplasmic reticulum stress response (protein disulfide isomerase A3, PDI), which are hallmarks of a possible P2Y receptor signalling pathway. Expression of P2Y receptors in RT4 D6P2T cells was demonstrated by RT-PCR and a transient elevation of intracellular calcium measured in response to UTP. Actin reorganisation was visualized after UTP treatment using phalloidin-FITC staining and was blocked by the P2Y antagonist suramin, which also inhibited Arp3, Rab GDI, and PDI protein upregulation. Our data indicate that extracellular UTP interacts with Schwann P2Y receptors and activates molecular machinery that induces changes in the glial cell cytoskeleton. PMID- 22065603 TI - Short stature due to 15q26 microdeletion involving IGF1R: report of an additional case and review of the literature. PMID- 22065604 TI - The conversion of nickel-bound CO into an acetyl thioester: organometallic chemistry relevant to the acetyl coenzyme A synthase active site. AB - When three become one: Within one nickel-based model system, the three reactants CO, MeI, and PhSH have been assembled to yield an acetyl thioester. The reactivity is of relevance for the functioning of the acetyl coenzyme A synthase active site and provides insights into possible binding sequences. PMID- 22065605 TI - In vivo magnetic resonance imaging tracking of SPIO-labeled human umbilical cord mesenchymal stem cells. AB - Human umbilical cord mesenchymal stem cells (hUC-MSCs) can be efficiently labeled by superparamagnetic iron oxide (SPIO) nanoparticles, which produces low signal intensity on magnetic resonance imaging (MRI) in vitro. This study was to evaluate the feasibility of in vivo tracking for hUC-MSCs labeled by SPIO with noninvasive MRI. SPIO was added to cultures at concentrations equivalent to 0, 7, 14, 28, and 56 ug Fe/ml (diluted with DMEM/F12) and incubated for 16 h. Prussian Blue staining was used to determinate the labeling efficiency. Rats were randomly divided into three groups, control group, hUC-MSCs group, and SPIO-labeled hUC MSCs group. All groups were subjected to spinal cord injury (SCI) by weight drop device. Rats were examined for neurological function. In vivo MRI was used to track SPIO-labeled hUC-MSCs transplanted in rats spinal cord. Survival and migration of hUC-MSCs were also explored using immunofluorescence. Significant improvements in locomotion were observed in the hUC-MSCs groups. There was statistical significance compared with control group. In vivo MRI 1 and 3 weeks after injection showed a large reduction in signal intensity in the region transplanted with SPIO-labeled hUC-MSCs. The images from unlabeled hUC-MSCs showed a smaller reduction in signal intensity. Transplanted hUC-MSCs engrafted within the injured rats spinal cord and survived for at least 8 weeks. In conclusion, hUC-MSCs can survive and migrate in the host spinal cord after transplantation, which promote functional recovery after SCI. Noninvasive imaging of transplanted SPIO-labeled hUC-MSCs is feasible. PMID- 22065606 TI - Investigation of the effect of hyperglycemia on intracerebral hemorrhage by proteomic approaches. AB - Intracerebral hemorrhage (ICH) is associated with high mortality and disability, and hyperglycemia worsens the clinical and neurological outcomes of patients with ICH. In this study, we utilized proteomic approaches to investigate the role of hyperglycemia in ICH. Hyperglycemia was induced by intraperitoneal injection of streptozotocin (STZ) in adult Sprague-Dawley male rats; ICH was induced by stereotaxic infusion of collagenase/heparin into the right striatum. It was observed that the size of induced hemorrhage was significantly larger in the hyperglycemic group (n=6 in each group). On the first day after ICH, an apparent decrease in the bilateral grasp was also observed for the lesioned hyperglycemic rats compared with normoglycemic ones. When employing 2-DE and MS to examine the proteomes of perihematomal and control regions in individual hyperglycemic and normoglycemic rats, eight differentially expressed protein targets were identified. Most noteworthy, in response to ICH significant increase of albumin was ubiquitously observed in the brains of normoglycemic rats but not in the brains of hyperglycemic rats. Coincidentally, more significant neuronal apoptosis were found in the perihematomal regions of hyperglycemic rats. These observations described suggest the protection role of albumin in acute stage of ICH, which may be dependent on different blood sugar levels. PMID- 22065607 TI - 8p21 microdeletion in a patient with intellectual disability and behavioral abnormalities. PMID- 22065608 TI - 2-[(E)-(6-Amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra-hydro-pyrimidin-5-yl)imino meth-yl]pyridinium bromide. AB - The title compound, C(12)H(14)N(5)O(2) (+).Br(-), is the hydro-bromide salt of a Schiff base in which protonation has taken place at the pyridine N atom. This organic cation is essentially planar (r.m.s. of all fitted non-H atoms = 0.0448 A). In the crystal, N-H?Br hydrogen bonds as well as C-H?O and C-H?Br inter actions connect the mol-ecules, forming a three-dimensional network. PMID- 22065609 TI - Gender roles and their influence on life prospects for women in urban Karachi, Pakistan: a qualitative study. AB - BACKGROUND: Pakistan is a patriarchal society where men are the primary authority figures and women are subordinate. This has serious implications on women's and men's life prospects. OBJECTIVE: The aim was to explore current gender roles in urban Pakistan, how these are reproduced and maintained and influence men's and women's life circumstances. DESIGN: Five focus group discussions were conducted, including 28 women representing employed, unemployed, educated and uneducated women from different socio-economic strata. Manifest and latent content analyses were applied. FINDINGS: TWO MAJOR THEMES EMERGED DURING ANALYSIS: 'Reiteration of gender roles' and 'Agents of change'. The first theme included perceptions of traditional gender roles and how these preserve women's subordination. The power gradient, with men holding a superior position in relation to women, distinctive features in the culture and the role of the extended family were considered to interact to suppress women. The second theme included agents of change, where the role of education was prominent as well as the role of mass media. It was further emphasised that the younger generation was more positive to modernisation of gender roles than the elder generation. CONCLUSIONS: This study reveals serious gender inequalities and human rights violations against women in the Pakistani society. The unequal gender roles were perceived as static and enforced by structures imbedded in society. Women routinely faced serious restrictions and limitations of autonomy. However, attainment of higher levels of education especially not only for women but also for men was viewed as an agent towards change. Furthermore, mass media was perceived as having a positive role to play in supporting women's empowerment. PMID- 22065610 TI - Gold(I)-1,3-diene complexes: connecting structure, bonding, and reactivity. PMID- 22065611 TI - Lectin capture strategy for effective analysis of cell secretome. AB - Secreted proteins play important roles in physiological and pathological processes. However, effective proteomic detection of low-abundant secreted proteins is often shielded by the presence of a large amount of intracellular proteins released from unavoidable dead cells during cell culture. In the present study, we applied lectin affinity capture approach to enrich the secreted proteins in the conditioned media (CM) of three human breast cell lines (MCF-10A, MCF-7, and MDA-MB-231). Lectin capture showed efficient enrichment of the secreted proteins in CM of all three cell lines and significantly increased the number of secreted proteins detected: from 183 to 292 for MCF-10A, 196 to 325 for MCF-7, and 194 to 368 for MDA-MB-231. Based on more comprehensive profiling of the secreted proteins, we identified 92 secreted proteins which were both upregulated in MCF-7 and MDA-MB-231, with 82 only found in lectin-captured samples. It should be noted that among these 82 potential biomarkers, 59 were not reported in the previous proteomic studies of breast cancer. These data indicate that the lectin capture approach is a powerful means to move toward more comprehensive analysis and comparison of secretomes. PMID- 22065612 TI - Striking phenotypic variability in familial TRPV4-axonal neuropathy spectrum disorder. PMID- 22065613 TI - Taming the Friedel-Crafts reaction: organocatalytic approach to optically active 2,3-dihydrobenzofurans. AB - Fine-tuning: Three types of optically active trans-2,3-disubstituted-2,3 dihydrobenzofurans having three contiguous stereogenic centers can be efficiently accessed by one-pot reaction cascades (see scheme; TMS = trimethylsilyl). High substitution diversity of the final products can be achieved from the same common precursors by fine-tuning of their reactivity through simple structural modifications. PMID- 22065614 TI - A newborn with overlapping features of AEC and EEC syndromes. AB - Ectrodactyly, ectodermal dysplasia, clefting (EEC) syndrome is the prototype of several p63 conditions, which include ankyloblepharon, ectodermal dysplasia, clefting (AEC) syndrome, limb-mammary syndrome (LMS), Rapp-Hodgkin syndrome (RHS), ADULT syndrome, and others. All these disorders include combinations of ectodermal dysplasia, orofacial clefting and limb malformations in variable severity. A newborn patient is presented with diffuse erythematous and desquamating skin lesions and anal atresia. She also had sparse and lightly colored thin hair, deeply set eyes, hypoplastic alae nasi, and a short philtrum. Cleft lip/palate and ankyloblepharon were not present. Complete cutaneous syndactyly was present on both hands in between the third and fourth fingers. Mild ectrodactyly was evident on all four extremities in between first and second digits. There was post-axial polydactyly on both feet. Anal atresia was present and defecation occurred through a rectovaginal fistula. The patient represented an interesting overlapping clinical condition between AEC and EEC syndromes. Diffuse skin lesions with excoriation and desquamation suggest AEC syndrome, despite the absence of ankyloblepharon, however; ectrodactyly and polydactyly strongly suggest the EEC syndrome. C308Y mutation in exon 8 of TP63 gene was detected, which was previously described to lead only to EEC syndrome and not to any of the other allelic conditions. These data emphasize the large degree of clinical variability that may be seen for specific TP63 mutations. PMID- 22065615 TI - Effect of mass spectrometric parameters on peptide and protein identification rates for shotgun proteomic experiments on an LTQ-orbitrap mass analyzer. AB - The success of a shotgun proteomic experiment relies heavily on the performance and optimization of both the LC and the MS systems. Despite this, little consideration has, so far, been given to the importance of evaluating and optimizing the MS instrument settings during data-dependent acquisition mode. Moreover, during data-dependent acquisition, the users have to decide and choose among various MS parameters and settings, making a successful analysis even more challenging. We have systematically investigated and evaluated the effect of enabling and disabling the preview mode for FTMS scan, the number of microscans per MS/MS scan, the number of MS/MS events, the maximum ion injection time for MS/MS, and the automatic gain control target value for MS and MS/MS events on protein and peptide identification rates on an LTQ-Orbitrap using the Saccharomyces cerevisiae proteome. Our investigations aimed to assess the significance of each MS parameter to improve proteome analysis and coverage. We observed that higher identification rates were obtained at lower ion injection times i.e. 50-150 ms, by performing one microscan and 12-15 MS/MS events. In terms of ion population, optimal automatic gain control target values were at 5*10(5) -1*10(6) ions for MS and 3*10(3) -1*10(4) ions for MS/MS. The preview mode scan had a minimal effect on identification rates. Using optimized MS settings, we identified 1038 (+/-2.3%) protein groups with a minimum of two peptide identifications and an estimated false discovery rate of ~1% at both peptide and protein level in a 160-min LC-MS/MS analysis. PMID- 22065616 TI - Molecular wheels of ruthenium and osmium with bridging chalcogenolate ligands: edge-shared-octahedron structures and metal-ion binding. AB - Inventing new wheels: reaction of [M(3)(CO)(12) ] (M=Ru, Os) with 4-RC(6)H(4)SH afforded [{M(S-4-RC(6)H(4))(2)(CO)(2)}(8)] (R=H; I) or [{M(S-4 RC(6)H(4))(2)(CO)(2)}(6)] (R=Me, iPr; II; see scheme), all of which have been structurally characterized. The octamers I are unique metal molecular wheels featuring skew-edge-shared octahedra with a central planar M(8) octagon. [{Ru(S-4 iPrC(6)H(4))(2)(CO)(2)}(6)] selectively binds a Cu(+) or Ag(+) ion to form [M'{Ru(S(4-iPr-C(6)H(4)))(2)(CO)(2)}(6)](+) (III). PMID- 22065617 TI - 4,4'-Bipyridine-3-(thio-phen-3-yl)acrylic acid (1/2). AB - In the title 1/2 adduct, C(10)H(8)N(2).2C(7)H(6)O(2)S, the dihedral angle between the pyridine rings is 18.41 (11) degrees . In the thio-phene-acrylic acid mol ecules, the dihedral angles between the respective thio-phene and acrylic acid units are 5.52 (17) degrees and 23.92 (9) degrees . In the crystal, the components are linked via O-H?N hydrogen-bonding inter-actions, forming units of two 3-thio-phene-acrylic acid mol-ecules and one 4,4'-bipyridine mol-ecule. PMID- 22065619 TI - Reassessment of oral frenula in Ehlers-Danlos syndrome: a study of 32 patients with the hypermobility type. PMID- 22065618 TI - Dissociation of response and feedback negativity in schizophrenia: electrophysiological and computational evidence for a deficit in the representation of value. AB - Contrasting theories of schizophrenia propose that the disorder is characterized by a deficit in phasic changes in dopamine activity in response to ongoing events or, alternatively, by a weakness in the representation of the value of responses. Schizophrenia patients have reliably reduced brain activity following incorrect responses but other research suggests that they may have intact feedback-related potentials, indicating that the impairment may be specifically response-related. We used event-related brain potentials and computational modeling to examine this issue by comparing the neural response to outcomes with the neural response to behaviors that predict outcomes in patients with schizophrenia and psychiatrically healthy comparison subjects. We recorded feedback-related activity in a passive gambling task and a time estimation task and error-related activity in a flanker task. Patients' brain activity following an erroneous response was reduced compared to comparison subjects but feedback-related activity did not differ between groups. To test hypotheses about the possible causes of this pattern of results, we used computational modeling of the electrophysiological data to simulate the effects of an overall reduction in patients' sensitivity to feedback, selective insensitivity to positive or negative feedback, reduced learning rate, and a decreased representation of the value of the response given the stimulus on each trial. The results of the computational modeling suggest that schizophrenia patients exhibit weakened representation of response values, possibly due to failure of the basal ganglia to strongly associate stimuli with appropriate response alternatives. PMID- 22065620 TI - 3-Hy-droxy-2-[(2E)-1-(2-hy-droxy-6-oxocyclo-hex-1-en-1-yl)-3-(2-meth-oxy-phen yl)prop-2-en-1-yl]cyclo-hex-2-en-1-one. AB - In the title compound, C(22)H(24)O(5), each of the cyclo-hexenone rings adopts a half-chair conformation. The hy-droxy and carbonyl O atoms face each other and are orientated to allow for the formation of the two intra-molecular O-H?O hydrogen bonds which are typical of xanthene derivatives. In the crystal, weak inter-molecular C-H?O hydrogen bonds link mol-ecules into layers parallel to the ab plane. PMID- 22065621 TI - Lewis acid catalyzed intramolecular [3+2] cross-cycloaddition of donor-acceptor cyclopropanes with carbonyls: a general strategy for the construction of acetal[n.2.1] skeletons. AB - Build a bridge: The first catalytic intramolecular [3+2] cycloaddition of monodonor-monoacceptor cyclopropanes (see scheme) provides a general and efficient strategy for construction of structurally diverse acetal[n.2.1] and 1,4 dioxygen-substituted cyclic skeletons, which are widely distributed in biologically important natural products. PMID- 22065622 TI - 2-Oxo-4-(thio-phen-2-yl)-1,2,5,6-tetra-hydro-benzo[h]quinoline-3-carbonitrile. AB - In the mol-ecule of the title compound, C(18)H(12)N(2)OS, the tetra-hydro benzo[h]quinoline fused-ring system is buckled owing to the ethyl-ene -CH(2)CH(2) fragment, the benzene ring and the pyridine ring being twisted by 16.0 (1) degrees . The 4-substituted aromatic ring is bent away from the pyridine ring by 59.5 (2) degrees (for the major disordered thienyl component) in order to avoid crowding the cyanide substituent. In the crystal, two mol-ecules are linked by a pair of N-H?O hydrogen bonds to form a centrosymmetric dimer. The thienyl ring is disordered over two sites in a 72.7 (2):27.3 ratio. PMID- 22065623 TI - N-[4-(7-Meth-oxy-2-oxo-2H-chromen-8-yl)-2-methyl-butan-2-yl]propionamide. AB - In the crystal structure of the title osthol derivative, C(18)H(23)NO(4), mol ecules are linked by N-H?O hydrogen bonds into an infinite chain running parallel to the c axis. The CH(3)CH(2)- atoms of the propionamide group are disordered over two sets of sites with refined occupancies of 0.689 (12) and 0.311 (12). PMID- 22065624 TI - 2-Oxo-4-phenyl-1,2,5,6-tetra-hydro-benzo[h]quinoline-3-carbonitrile. AB - In the mol-ecule of the title compound, C(20)H(14)N(2)O, the tetra-hydro benzo[h]quinoline fused-ring system is buckled owing to the ethyl-ene -CH(2)CH(2) fragment, the benzene ring and the pyridine ring being twisted by 19.7 (1) degrees . The 4-substituted aromatic ring is bent away from the pyridine ring by 62.9 (1) degrees in order to avoid crowding the cyanide substituent. In the crystal, two mol-ecules are linked by a pair of N-H?O hydrogen bonds to form a centrosymmetric dimer. PMID- 22065625 TI - The box C/D and H/ACA snoRNPs: key players in the modification, processing and the dynamic folding of ribosomal RNA. AB - Box C/D and H/ACA RNPs are essential ribonucleoprotein particles that are found throughout both eukaryotes [small nucleolar RNPs (snoRNPs)] and archaea [snoRNP like complexes (sRNPs)]. These complexes catalyze the site-specific pseudouridylation and most of the methylation of ribosomal RNA (rRNA). The numerous modifications, which are clustered in functionally important regions of the rRNA, are important for rRNA folding and ribosome function. The RNA component of the complexes [small nucleolar RNA (snoRNA) or small RNA (sRNA)] functions in substrate binding by base pairing with the target site and as a scaffold coordinating the organization of the complex. In eukaryotes, a subset of snoRNPs do not catalyze modification but, through base pairing to the rRNA or flanking precursor sequences, direct pre-rRNA folding and are essential for rRNA processing. In the last few years there have been significant advances in our understanding of the structure of archaeal sRNPs. High resolution structures of the archaeal C/D and H/ACA sRNPs have not only provided a detailed understanding of the molecular architecture of these complexes but also produced key insights into substrate binding and product release. In both cases, this is mediated by significant movement in the complexes. Advances have also been made in our knowledge of snoRNP recruitment and release from pre-ribosome complexes in eukaryotes. New snoRNA-rRNA interactions have been documented, and the roles of RNA helicases in releasing snoRNP complexes from the rRNA have been described. PMID- 22065626 TI - Writers cramp in office workers-an epidemiologic and psychosomatic study. AB - The study is aimed at investigating the occurrence of writers cramp in office workers, drawn from ten major offices of Kanpur to determine the nature and relationship of various emotional factors in the development of this disability. The observations on writers cramp cases were compared with a group of normal and diseased controls. Out of a surveyed population of 3,325 office workers, there were 18 cases of writers cramp. Cramp cases scored significantly higher on all the subscales of Middlesex hospital questionnaire than the diseased and normal controls. Emotional stress of sufficient intensity was recorded in an increased percentage (66.70%) of writers cramp cases as compared to diseased and normal controls (53.3% and 46.7% respectively). The most frequent area of disturbance was severe maladjustment found in 38.9% of writers cramp cases, while in diseased and normal controls the type of stresses were of a different nature. PMID- 22065627 TI - 2-[(1R,3S)-6,7-Dimeth-oxy-1-phenyl-1,2,3,4-tetra-hydro-isoquinolin-3-yl]-4-phenyl 1,3-thia-zole. AB - In the title compound, C(26)H(24)N(2)O(2)S, the dihedral angle between the thia zole ring and the adjacent phenyl ring is 3.02 (15) degrees . The N-containing six-membered ring of the tetra-hydro-isoquinoline unit adopts a half-chair conformation. The dihedral angle between the least-squares plane of the tetra hydro-isoquinoline ring system and its nearest phenyl ring is 76.90 (13) degrees . No classical hydrogen bonds nor pi-pi inter-actions were found in the crystal structure. PMID- 22065628 TI - Single-domain parvulins constitute a specific marker for recently proposed deep branching archaeal subgroups. AB - Peptidyl-prolyl cis/trans isomerases (PPIases) are enzymes assisting protein folding and protein quality control in organisms of all kingdoms of life. In contrast to the other sub-classes of PPIases, the cyclophilins and the FK-506 binding proteins, little was formerly known about the parvulin type of PPIase in Archaea. Recently, the first solution structure of an archaeal parvulin, the PinA protein from Cenarchaeum symbiosum, was reported. Investigation of occurrence and frequency of PPIase sequences in numerous archaeal genomes now revealed a strong tendency for thermophilic microorganisms to reduce the number of PPIases. Single domain parvulins were mostly found in the genomes of recently proposed deep branching archaeal subgroups, the Thaumarchaeota and the ARMANs (archaeal Richmond Mine acidophilic nanoorganisms). Hence, we used the parvulin sequence to reclassify available archaeal metagenomic contigs, thereby, adding new members to these subgroups. A combination of genomic background analysis and phylogenetic approaches of parvulin sequences suggested that the assigned sequences belong to at least two distinct groups of Thaumarchaeota. Finally, machine learning approaches were applied to identify amino acid residues that separate archaeal and bacterial parvulin proteins from each other. When mapped onto the recent PinA solution structure, most of these positions form a cluster at one site of the protein possibly indicating a different functionality of the two groups of parvulin proteins. PMID- 22065629 TI - Methyl rac-(2R,11S,12R)-12-(2-chloro-phen-yl)-22-oxo-9,13,21-trioxapenta-cyclo [12.8.0.0.0.0]docosa-1(14),3,5,7,15(20),16,18-hepta-ene-11-carboxyl-ate. AB - In the title compound C(27)H(19)ClO(6), the coumarin ring system is not exactly planar, with a dihedral angle of 4.12 (7) degrees between its benzene and lactone rings. The cis-fused pyran rings adopt half-chair conformations. The carbometh-oxy and chloro-phenyl groups are in a trans configuration. The crystal packing is stabilized by inter-molecular C-H?O interactions, which produce a centrosymmetric R(2) (2)(14) dimer and two centrosymmetric R(2) (2)(18) dimers connecting the mol-ecules in a two-dimensional fashion. PMID- 22065630 TI - catena-Poly[[silver(I)-MU-bis-{2-[(E)-phenyl-diazen-yl]-1H-imidazol-1-yl}methane] trifluoro-methane-sulfonate]. AB - The title compound, {[Ag(C(19)H(16)N(8))](CF(3)SO(3))}(n), is a coordin-ation polymer with cationic chain motif. The Ag(+) cation is coordinated by two unsubstituted imidazolyl N atoms of two independent 2-paBIM ligands [2-paBIM is bis-{2-[(E)-phenyl-diazen-yl]-1H-imidazol-1-yl}methane]. The shortest Ag?Ag separation in a cationic chain is 8.841 (2) A and the dihedral angle between two 2-phenyl-diazenyl-imidazole planes in the same ligand is 74.7 (3) degrees . Weak C-H?O interactions are seen in the crystal. PMID- 22065631 TI - 2-(2-Hy-droxy-phen-yl)-3,4-dihydro-iso-quinolin-1(2H)-one. AB - There are two independent mol-ecules in the asymmetric unit of the title compound, C(15)H(13)NO(2), in both the six-membered dihydro-pyridine rings adopt a half-chair conformation. The two benzene rings make dihedral angles of 43.66 (10) and 62.22 (10) degrees in the two mol-ecules. In the crystal, the two independent mol-ecules are linked alternately by inter-molecular O-H?O hydrogen bonds, forming a zigzag chain along the c axis. Furthermore, inter-molecular C H?pi inter-actions link the chains into a three-dimensional network. PMID- 22065632 TI - (Z)-4-[(2-Amino-anilino)(phen-yl)methyl-idene]-3-methyl-1-phenyl-1H-pyrazol-5(4H) one. AB - The mol-ecule of the title compound, C(23)H(20)N(4)O, assumes a non-planar conformation in which the pyrazolone ring forms dihedral angles of 10.33 (11), 65.34 (11) and 63.52 (10) degrees with the three benzene rings. In the crystal, the mol-ecules are linked by inter-molecular N-H?N hydrogen bonds, generating chains parallel to the b axis. The secondary amino group is involved in an intra molecular N-H?O hydrogen bond. PMID- 22065633 TI - 4-Meth-oxy-anilinium nitrate. AB - The title compound, C(7)H(10)NO(+).NO(3) (-), crystallized with two p-ansidinium cations and two nitrate anions in the asymmetric unit. As well as Columbic and van der Waals forces, moleucles inter-act via multiple bifurcated N-H?O hydrogen bonds that help consolidate the crystal packing, resulting in a three-dimensional network. PMID- 22065634 TI - catena-Poly[[diaquaterbium(III)]-tetrakis(MU(2)-pyridine-4-carboxylato-kappaO:O') [diaquaterbium(III)]-bis(MU(2)-pyridine-4-carboxylato-kappaO:O')]. AB - The title complex, [Tb(2)(C(6)H(4)NO(2))(6)(H(2)O)(4)](n), was isolated under hydro-thermal conditions using the ligand pyridine-4-carb-oxy-lic acid (HL) and Tb(2)O(3). The deprotonated L(2-) ligands adopt bridging coordination modes. The central Tb(III) atom is bridged by L(2-) ligands, forming a polymeric chain parallel to the a axis. Supra-molecular O-H?N inter-actions link the chains, building up a layer parallel to (010). O-H?O hydrogen bonds also occur. Two of the pyridine rings are disordered by rotation around the central C-N direction with occupancy ratios of 0.53 (1):0.47 (1). PMID- 22065635 TI - 6-(4-Meth-oxy-phen-yl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-carbaldehyde. AB - The 4-meth-oxy-phenyl residue in the title compound, C(21)H(19)NO(2), is oriented at a dihedral angle of 54.6 (5) degrees with respect to the phenyl ring and at a dihedral angle of 52.5 (8) degrees with respect to the pyrrole ring of the pyrrolizine system. The phenyl ring is oriented at a dihedral angle of 36.2 (5) degrees with respect to the pyrrole ring. The meth-oxy group makes a C-C-O-C torsion angle of 3.8 (9) degrees with the attached benzene ring. PMID- 22065636 TI - An intramolecular salt bridge drives the soluble domain of GTP-bound atlastin into the postfusion conformation. AB - Endoplasmic reticulum (ER) network branching requires homotypic tethering and fusion of tubules mediated by the atlastin (ATL) guanosine triphosphatase (GTPase). Recent structural studies on the ATL soluble domain reveal two dimeric conformers proposed to correspond to a tethered prefusion state and a postfusion state. How the prefusion conformer transitions to the postfusion conformer is unknown. In this paper, we identify an intramolecular salt bridge mediated by two residues outside the GTPase domain near the point of rotation that converts the prefusion dimer to the postfusion state. Charge reversal of either residue blocked ER network branching, whereas a compensatory charge reversal to reestablish electrostatic attraction restored function. In vitro assays using the soluble domain revealed that the salt bridge was dispensable for GTP binding and hydrolysis but was required for forming the postfusion dimer. Unexpectedly, the postfusion conformation of the soluble domain was achieved when bound to the nonhydrolyzable GTP analogue guanosine 5'-[beta,gamma-imido]triphosphate, suggesting that nucleotide hydrolysis might not be required for the prefusion to postfusion conformational change. PMID- 22065637 TI - Hsp42 is required for sequestration of protein aggregates into deposition sites in Saccharomyces cerevisiae. AB - The aggregation of proteins inside cells is an organized process with cytoprotective function. In Saccharomyces cerevisiae, aggregating proteins are spatially sequestered to either juxtanuclear or peripheral sites, which target distinct quality control pathways for refolding and degradation. The cellular machinery driving the sequestration of misfolded proteins to these sites is unknown. In this paper, we show that one of the two small heat shock proteins of yeast, Hsp42, is essential for the formation of peripheral aggregates during physiological heat stress. Hsp42 preferentially localizes to peripheral aggregates but is largely absent from juxtanuclear aggregates, which still form in hsp42Delta cells. Transferring the amino-terminal domain of Hsp42 to Hsp26, which does not participate in aggregate sorting, enables Hsp26 to replace Hsp42 function. Our data suggest that Hsp42 acts via its amino-terminal domain to coaggregate with misfolded proteins and perhaps link such complexes to further sorting factors. PMID- 22065638 TI - Existence of a novel clathrin-independent endocytic pathway in yeast that depends on Rho1 and formin. AB - Yeast is a powerful model organism for dissecting the temporal stages and choreography of the complex protein machinery during endocytosis. The only known mechanism for endocytosis in yeast is clathrin-mediated endocytosis, even though clathrin-independent endocytic pathways have been described in other eukaryotes. Here, we provide evidence for a clathrin-independent endocytic pathway in yeast. In cells lacking the clathrin-binding adaptor proteins Ent1, Ent2, Yap1801, and Yap1802, we identify a second endocytic pathway that depends on the GTPase Rho1, the downstream formin Bni1, and the Bni1 cofactors Bud6 and Spa2. This second pathway does not require components of the better-studied endocytic pathway, including clathrin and Arp2/3 complex activators. Thus, our results reveal the existence of a second pathway for endocytosis in yeast, which suggests similarities with the RhoA-dependent endocytic pathways of mammalian cells. PMID- 22065639 TI - Cdk1 phosphorylation of the kinetochore protein Nsk1 prevents error-prone chromosome segregation. AB - Cdk1 controls many aspects of mitotic chromosome behavior and spindle microtubule (MT) dynamics to ensure accurate chromosome segregation. In this paper, we characterize a new kinetochore substrate of fission yeast Cdk1, Nsk1, which promotes proper kinetochore-MT (k-MT) interactions and chromosome movements in a phosphoregulated manner. Cdk1 phosphorylation of Nsk1 antagonizes Nsk1 kinetochore and spindle localization during early mitosis. A nonphosphorylatable Nsk1 mutant binds prematurely to kinetochores and spindle, cementing improper k MT attachments and leading to high rates of lagging chromosomes that missegregate. Accordingly, cells lacking nsk1 exhibit synthetic growth defects with mutations that disturb MT dynamics and/or kinetochore structure, and lack of proper phosphoregulation leads to even more severe defects. Intriguingly, Nsk1 is stabilized by binding directly to the dynein light chain Dlc1 independently of the dynein motor, and Nsk1-Dlc1 forms chainlike structures in vitro. Our findings establish new roles for Cdk1 and the Nsk1-Dlc1 complex in regulating the k-MT interface and chromosome segregation. PMID- 22065640 TI - Cryoelectron tomography of radial spokes in cilia and flagella. AB - Radial spokes (RSs) are ubiquitous components in the 9 + 2 axoneme thought to be mechanochemical transducers involved in local control of dynein-driven microtubule sliding. They are composed of >23 polypeptides, whose interactions and placement must be deciphered to understand RS function. In this paper, we show the detailed three-dimensional (3D) structure of RS in situ in Chlamydomonas reinhardtii flagella and Tetrahymena thermophila cilia that we obtained using cryoelectron tomography (cryo-ET). We clarify similarities and differences between the three spoke species, RS1, RS2, and RS3, in T. thermophila and in C. reinhardtii and show that part of RS3 is conserved in C. reinhardtii, which only has two species of complete RSs. By analyzing C. reinhardtii mutants, we identified the specific location of subsets of RS proteins (RSPs). Our 3D reconstructions show a twofold symmetry, suggesting that fully assembled RSs are produced by dimerization. Based on our cryo-ET data, we propose models of subdomain organization within the RS as well as interactions between RSPs and with other axonemal components. PMID- 22065641 TI - Tim50's presequence receptor domain is essential for signal driven transport across the TIM23 complex. AB - N-terminal targeting signals (presequences) direct proteins across the TOM complex in the outer mitochondrial membrane and the TIM23 complex in the inner mitochondrial membrane. Presequences provide directionality to the transport process and regulate the transport machineries during translocation. However, surprisingly little is known about how presequence receptors interact with the signals and what role these interactions play during preprotein transport. Here, we identify signal-binding sites of presequence receptors through photo-affinity labeling. Using engineered presequence probes, photo cross-linking sites on mitochondrial proteins were mapped mass spectrometrically, thereby defining a presequence-binding domain of Tim50, a core subunit of the TIM23 complex that is essential for mitochondrial protein import. Our results establish Tim50 as the primary presequence receptor at the inner membrane and show that targeting signals and Tim50 regulate the Tim23 channel in an antagonistic manner. PMID- 22065642 TI - Dichlorido[1-(2,6-dimethyl-phenyl-imino)-1,2-diphenyl-propan-2-ol kappaN,O]palladium(II) methanol monosolvate. AB - The title compound, [PdCl(2)(C(23)H(23)NO)].CH(3)OH, was obtained by the reaction of 1-(2,6-dimethyl-phenyl-imino)-1,2-diphenyl-propan-2-ol and palladium chloride in methanol. The Pd atom is four-coordinated by the O atom of a tertiary alcohol, the imine N atom of the hy-droxy-limine part of the bidentate ligand and by two chloride ions, forming a nearly square-planar geometry. The complex mol-ecule and the uncoordinated methanol mol-ecule are connected via an O-H?O hydrogen bond. PMID- 22065643 TI - catena-Poly[[tetra-kis-(hexa-methyl-phospho-ramide-kappaO)bis-(nitrato kappaO,O')yttrium(III)] [silver(I)-di-MU-sulfido-molybdenum(VI)-di-MU-sulfido]]. AB - In the cation of the title compound, {[Y(NO(3))(2)(C(6)H(18)N(3)OP)(4)][AgMoS(4)]}(n), the Y atom is coordinated by eight O atoms from two chelating nitrate groups and four hexa-methyl-phospho ramide (hmp) ligands, which gives rise to a distorted square-anti-prismatic environment. Together with the two nitrate ligands, the overall charge for the complex cation is +1, which leads to the anionic chain having a monovalent repeat unit. The polymeric anionic chain, with Mo-Ag-Mo and Ag-Mo-Ag angles of 161.916 (13) and 153.915 (13) degrees , respectively, presents a distorted linear configuration. The cations and the anions are linked via weak C-H?S hydrogen bonding inter-actions while the cations exhibit inter-molecular C-H?O inter actions. The structure is isotypic with the corresponding W, Yb, Eu, Nd, La and Dy complexes. PMID- 22065644 TI - (Acetyl-acetonato-kappaO,O')bis-[5-meth-oxy-2-(naphth[1,2-d][1,3]oxazol-2 yl)phenyl-kappaC,N]iridium(III). AB - In the title compound, [Ir(C(18)H(12)NO(2))(2)(C(5)H(7)O(2))], the Ir atom is O,O'-chelated by the acetyl-acetonate group and C,N-chelated by the 2-aryl naphth[1,2-d]oxazole groups. The six-coordinate metal atom displays a distorted octa-hedral geometry. Intra-molecular C-H?O hydrogen bonds occur. In the crystal, inter-molecular C-H?O hydrogen bonds link the mol-ecules into columns parallel to the b axis. PMID- 22065645 TI - A cocrystal strategy to tune the luminescent properties of stilbene-type organic solid-state materials. AB - The one- and two-photon luminescence of stilbene-type solid-state materials can be tuned and controlled from blue to yellow color by a supramolecular cocrystal method. PMID- 22065646 TI - Application of Barluenga Boronic Coupling (BBC) to the parallel synthesis of drug like and drug fragment-like molecules. PMID- 22065647 TI - Practical synthesis of photochromic diarylethenes in integrated flow microreactor systems. AB - An effective method for the synthesis of photochromic diarylethenes through the generation of heteroaryllithiums and subsequent reaction with octafluorocyclopentene has been developed by using integrated flow microreactor systems. Reactions can be conducted without using cryogenic conditions by virtue of effective temperature and residence time control, although much lower temperatures (<-78 degrees C) are needed for batch macroreactions. Moreover, the synthesis of unsymmetrical diarylethenes, which is difficult to achieve when using conventional batch macrosystems, has been accomplished based on the selective introduction of one aryl group to give arylheptafluorocyclopentene followed by the introduction of another aryl group. The productivity of the laboratory-scale system is approximately 0.5 mmol min(-1). Therefore, the present integrated flow microreactor method serves as a practical way of synthesizing various photochromic diarylethene derivatives. PMID- 22065648 TI - Long-range attraction in aqueous colloidal suspensions. AB - Long-range attractions in aqueous suspensions were observed between polymeric microspheres and also between microspheres and a gel bead. Attractive displacements were consistently seen even between like-charged entities, and they were observed over spans as large as 2 mm. Such behaviors are unexpected, and may reside in a long-range attraction mechanism. PMID- 22065649 TI - Quantum rod-sensitized solar cells. PMID- 22065650 TI - Bis(eta-1-tert-butyl-inden-yl)nickel(II). AB - The title compound, [Ni(C(13)H(15))(2)], shows a slightly distorted sandwich structure with two independent mol-ecules in the asymmetric unit. Both Ni atoms are located on crystallographic centres of inversion. PMID- 22065651 TI - [(2R,3S,6S)-3-Acet-yloxy-6-(1-phenyl-1H-1,2,3-triazol-4-yl)-3,6-dihydro-2H-pyran 2-yl]methyl acetate. AB - In the title compound, C(18)H(19)N(3)O(5), the 3,6-dihydro-2H-pyran ring adopts a half-chair, distorted towards a half-boat, conformation with Q(T) = 0.5276(14) A. The benzene ring is twisted out of the place of the triazole ring [dihedral angle = 23.54 (8) degrees ]. In the crystal, supra-molecular layers in the ac plane are formed through C-H?O and C-H?pi(triazole) inter-actions. These stack along the b axis being connected by C-H?N contacts. PMID- 22065652 TI - Post-thyroidectomy dysphonia in patients with bilateral resection of the superior laryngeal nerve: a comparative spectrographic study. AB - The most serious complications of total thyroidectomy, in cases of widespread and invasive diseases, are mainly hypoparathyroidism and laryngeal inferior nerve palsy. Lesions of the external branch of superior laryngeal nerve instead, although less obvious than the those caused by the recurrent laryngeal nerve lesions, have been taken less into consideration. The frequency of this lesion varies from 14% to 20% of cases, although in reality it is underestimated; in fact, on the one hand it is difficult to assess this, and on the other, post thyroidectomy dysphonia is often considered inevitable. In the present retrospective research, 15 thyroidectomized patients (4 male, 11 female), have been subjected to qualitative and quantitative evaluation of the voice. Of these, 7 had a nerve lesion, while 8 did not. All the patients received a self evaluation voice questionnaire (VHI). In all cases, a videolaryngostroboscopy has been carried out and the voice acoustic features examined through a spectrographic analysis. The results showed that removal of the thyroid, at the end of a 12-month post-surgery period, still causes an impact on the qualitative and quantitative aspects of the vocal function, whether the superior larynx nerve was injured or not. The majority of the patients, in both groups, reported that their voice had worsened in quality and durability. Hence, we have shown that the patients with upper larynx nerve lesion have an alteration of F0, show a lower energy level and a modified spectrographic quality compared to patients without injury. This low voice is often considered by patients as a normal consequence of thyroid surgery. The present research confirms that the attempt to identify and protect the superior laryngeal nerve is essential to prevent post-thyroidectomy dysphonia, but this is not sufficient to obtain the best results because of the existence of muscular and psychogenic factors that reduce the still voice capacity of the patient. PMID- 22065653 TI - 3-Amino-1-methyl-9,10-dihydro-phenanthrene-2,4-dicarbonitrile. AB - The asymmetric unit of the title compound, C(17)H(13)N(3), contains two independent mol-ecules, which are non-planar as they are buckled owing to the ethyl-ene portion. The dihedral angle between the benzene rings is 26.4 (1) degrees in one mol-ecule and 32.9 (1) degrees in the other. In the crystal, the mol-ecules are disposed about a false inversion center, and are linked by two N H?N hydrogen bonds, generating a dimer. The dimers are linked by further N-H?N hydrogen bonds, resulting in a chain that runs along the longest axis of the ortho-rhom-bic unit cell. PMID- 22065654 TI - Propane-1,3-diaminium bis-(pyridine-4-carboxyl-ate) monohydrate. AB - The asymmetric unit of the title compound, C(3)H(12)N(2) (2+).2C(6)H(4)NO(2) ( ).H(2)O, consists of half of a doubly protonated propane-1,3-diammonium dication, a pyridine-4-carboxyl-ate anion and half of a solvent water mol-ecule; the dication and the solvent water are located on a twofold rotation axis which passes through the central C atom of the dication and the water O atom. The carboxyl-ate group of the anion appears to be delocalized on the basis of the C-O bond lengths. In the crystal, the components are linked by inter-molecular N-H?O, N-H?N and O-H?O hydrogen bonds. PMID- 22065655 TI - 3-(4-Nitro-phen-yl)-1H-1,2,4-triazole-5(4H)-thione. AB - In the title compound, C(8)H(6)N(4)O(2)S, the 1,2,4-triazole ring and the nitro group form dihedral angles of 6.26 (13) and 9.5 (3) degrees , respectively, with the phenyl ring. In the crystal, the mol-ecules are linked via pairs of N-H?S hydrogen bonds, generating [010] chains which contain R(2) (2) (8) ring motifs. The crystal structure is further stabilized by pi-pi stacking [centroid-centroid distance = 3.5491 (14) A] inter-actions. PMID- 22065656 TI - 2-Bromo-N-(2-hy-droxy-5-methyl-phen-yl)-2-methyl-propanamide. AB - In the title mol-ecule, C(11)H(14)BrNO(2), there is twist between the mean plane of the amide group and the benzene ring [the C-N-C-C torsion angle is -172.1 (2) degrees ]. The amide H atom forms an intra-molecular hydrogen bond with the Br atom. In the crystal, inter-molecular O-H?O and weak C-H?O hydrogen bonds link mol-ecules into a chain along [100]. PMID- 22065657 TI - Prognostic effect size of cardiovascular biomarkers in datasets from observational studies versus randomised trials: meta-epidemiology study. AB - OBJECTIVE: To compare the reported effect sizes of cardiovascular biomarkers in datasets from observational studies with those in datasets from randomised controlled trials. DESIGN: Review of meta-analyses. STUDY SELECTION: Meta analyses of emerging cardiovascular biomarkers (not part of the Framingham risk score) that included datasets from at least one observational study and at least one randomised controlled trial were identified through Medline (last update, January 2011). DATA EXTRACTION: Study-specific risk ratios were extracted from all identified meta-analyses and synthesised with random effects for (a) all studies, and (b) separately for observational and for randomised controlled trial populations for comparison. RESULTS: 31 eligible meta-analyses were identified. For seven major biomarkers (C reactive protein, non-HDL cholesterol, lipoprotein(a), post-load glucose, fibrinogen, B-type natriuretic peptide, and troponins), the prognostic effect was significantly stronger in datasets from observational studies than in datasets from randomised controlled trials. For five of the biomarkers the effect was less than half as strong in the randomised controlled trial datasets. Across all 31 meta-analyses, on average datasets from observational studies suggested larger prognostic effects than those from randomised controlled trials; from a random effects meta-analysis, the estimated average difference in the effect size was 24% (95% CI 7% to 40%) of the overall biomarker effect. CONCLUSIONS: Cardiovascular biomarkers often have less promising results in the evidence derived from randomised controlled trials than from observational studies. PMID- 22065658 TI - Why do the results of randomised and observational studies differ? PMID- 22065659 TI - Doctors in Israeli detention facilities are complicit in torture, says report. PMID- 22065660 TI - Extent of Dutch psychologist's research fraud was "unprecedented". PMID- 22065661 TI - Surgeon's return to work highlights need for urgent reform of GMC. PMID- 22065662 TI - Care in the community is an "unfinished revolution," says think tank. PMID- 22065663 TI - GMC rules against doctor who used unconventional tests and treatments for chronic fatigue syndrome. PMID- 22065664 TI - 2-[5-(4-Meth-oxy-phen-yl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-6-methyl-1,3 benzothia-zole. AB - In the title compound, C(24)H(21)N(3)OS, the pyrazole ring makes dihedral angles of 5.40 (7) and 6.72 (8) degrees with the benzo[d]thiazole ring system and the benzene ring, respectively, and a dihedral angle of 85.72 (8) degrees with the meth-oxy-substituted benzene ring. In the crystal structure, the mol-ecules are linked by C-H?pi inter-actions. PMID- 22065665 TI - 'FOLIE A DEUX': (A Case Report from Kenya). AB - The author presents the first case report of folie a deux from Saharan Africa. The clinical presentation of this disorder in Africa does not significantly differ from those reported elsewhere. But cultural factors like superstitions and witchcraft play an important role in the management of these patients. In the author's view, cooperation with the traditional healer with simultaneous administration of modern drugs may be the ideal way to treat such patients. PMID- 22065667 TI - Risks of cardiac imaging. PMID- 22065669 TI - 2-Methyl-1H-benzimidazol-3-ium hydrogen phthalate. AB - The asymmetric unit of the title compound, C(8)H(9)N(2) (+).C(8)H(5)O(4) (-), contains two independent ion pairs. In each 2-methyl-1H-benzimidazolium ion, an intra-molecular O-H?O bond forms an S(7) graph-set motif. In the crystal, the components are linked by N-H?O hydrogen bonds, forming chains along [210]. Further stabilization is provided by weak C-H?O hydrogen bonds. PMID- 22065670 TI - Hyperprolactinemia: An often missed cause of male infertility. PMID- 22065671 TI - Redetermination of (E)-3-(anthracen-9-yl)-1-(2-hy-droxy-phen-yl)prop-2-en-1-one. AB - The redetermined structure of title chalcone derivative, C(23)H(16)O(2), corrects errors in the title, scheme and synthesis in the previous report of the same structure [Jasinski et al. (2011 ?). Acta Cryst. E67, o795]. There are two independent mol-ecules in the asymmetric unit with slight differences in bond lengths and angles. The dihedral angle between the benzene ring and the anthracene ring system is 73.30 (4) degrees in one mol-ecule and 73.18 (4) degrees in the other. Both mol-ecules feature an intra-molecular O-H?O hydrogen bond, which generates an S(6) ring. In the crystal, mol-ecules are arranged into sheets lying parallel to the ac plane and further stacked along the b axis by pi pi inter-actions with centroid-centroid distances in the range 3.6421 (6)-3.7607 (6) A. The crystal structure is further stabilized by C-H?pi inter-actions. There are also C?O [3.2159 (15) A] short contacts. PMID- 22065672 TI - Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. AB - Adjuvants are critical for the success of vaccines. Agonists of microbial pattern recognition receptors (PRRs) are promising new adjuvant candidates. A mechanism through which adjuvants enhance immune responses is to stimulate innate immunity. We studied the innate immune response in humans to synthetic double-stranded RNA (polyinosinic:polycytidylic acid [poly IC] stabilized with poly-L-lysine [poly ICLC]), an agonist for toll-like receptor (TLR) 3, and the cytosolic RNA helicase MDA-5. Transcriptional analysis of blood samples from eight volunteers, after subcutaneous administration of poly ICLC, showed up-regulation of genes involved in multiple innate immune pathways in all subjects, including interferon (IFN) and inflammasome signaling. Blocking type I IFN receptor ex vivo significantly dampened the response to poly IC. Comparative transcriptional analysis showed that several innate immune pathways were similarly induced in volunteers immunized with the highly efficacious yellow fever vaccine. Therefore, a chemically defined PRR agonist like poly ICLC can be a reliable and authentic microbial mimic for inducing innate immune responses in humans. PMID- 22065673 TI - Register shifting of an insulin peptide-MHC complex allows diabetogenic T cells to escape thymic deletion. AB - In nonobese diabetic (NOD) mice, two sets of autoreactive CD4(+) T cells recognize the B:9-23 segment of the insulin B chain. One set, type A, recognizes insulin presented by antigen-presenting cells (APCs). These T cells are highly deleted in the thymus. The second set, type B, does not recognize insulin protein but reacts with soluble B chain peptide. This set is not deleted in the thymus but is activated in the islets of Langerhans. In this study, we examine the specificity of these two types of T cells. The protein-reactive set recognizes the stretch of residues 13-21 of the insulin B chain. The set reactive to peptide only recognizes the stretch from residues 12-20. A single amino acid shift of the B chain peptide bound to I-A(g7) determines whether T cells recognize peptides generated by the processing of insulin, and consequently their escape from thymic purging. Biochemical experiments indicate that peptides bound in the 13-21 register interact more favorably with I-A(g7) than peptides that bind in the 12 20 register. Thus, self-reactive T cells can become pathogenic in the target organ where high concentrations of antigen and/or differences in intracellular processing present peptides in registers distinct from those found in the thymus. PMID- 22065674 TI - Diaqua-bis-(5-methyl-pyrazine-2-carboxyl-ato-kappaN,O)cadmium. AB - In the title compound, [Cd(C(6)H(5)N(2)O(2))(2)(H(2)O)(2)], the Cd(II) ion is coordinated in a severely distorted octa-hedral geometry. The N atoms are cis to each other, while the water O atoms and ligand O atoms are mutually trans. The crystal structure is stabilized by a network of O-H?O, O-H?N and C-H?O hydrogen bonds and pi-pi stacking inter-actions [centroid-centroid distances = 3.730 (3) and 3.652 (3) A] between the 5-methyl-pyrazine-2-carboxyl-ate ligands. The structure is isotypic with the manganese analog. PMID- 22065675 TI - HTLV-2 APH-2 expression is correlated with proviral load but APH-2 does not promote lymphocytosis. AB - We recently discovered the antisense protein of human T-cell leukemia virus (HTLV) type 2 (APH-2), whose messenger RNA is encoded by the antisense strand of the HTLV-2 genome. We quantified proviral load, level of tax, and APH-2 in a series of blood samples obtained from a cohort of HTLV-2 carriers. We determined whether APH-2 promotes cell proliferation. APH-2 was detectable in most samples tested and was correlated with proviral load. APH-2 levels were not correlated with lymphocyte count in vivo, consistent with the inability of APH-2 to promote cell proliferation in vitro. APH-2 does not promote cell proliferation and does not cause lymphocytosis. PMID- 22065676 TI - Backing the wrong horse. PMID- 22065677 TI - The ICMJE's definition of authorship is illogical and unethical. PMID- 22065678 TI - GlaxoSmithKline pays $3bn to settle dispute over rosiglitazone and other drugs. PMID- 22065679 TI - UK government spends 2m pound to raise awareness of dementia. PMID- 22065680 TI - Something in the water. PMID- 22065681 TI - Organisations challenge basis for recommending HPV vaccine for boys. PMID- 22065682 TI - India's experience of using recycled pacemakers could benefit other countries. PMID- 22065683 TI - Bad medicine: adult attention-deficit/hyperactivity disorder. PMID- 22065684 TI - Breast cancer surgeon is struck off because of risk to patients. PMID- 22065685 TI - [Bis-(4-methyl-1,3-thia-zol-2-yl-kappaN)methane]-tricarbonyl-dichlorido tungsten(II). AB - The title compound, [WCl(2)(C(9)H(10)N(2)S(2))(CO)(3)], is a hepta-coordinate tungsten(II) complex with a capped-octa-hedral coordination sphere in which one CO ligand caps a face formed by a chloro ligand and the two other carbonyls. The chloro ligands are mutually trans positioned at an angle of 156.98 (7) degrees . The chelating bis-(4-methyl-1,3-thia-zol-2-yl)methane ligand coordinates with the imine N atoms. In the crystal, mol-ecules are linked into chains parallel to [201] by weak C-H?O contacts between the CH(2) group of the bis-(4-methyl-thia zol-2-yl)methane ligand and the O atom of the capping CO group. PMID- 22065686 TI - The ethics of the affordability of health insurance. AB - In this essay we argue that the concept of affordable health insurance is rooted in a social obligation to protect fair equality of opportunity. Specifically, health insurance plays a limited but significant role in protecting opportunity in two ways: it helps keep people functioning normally and it protects their financial security. Together these benefits enable household members to exercise reasonable choices about their plans of life. To achieve truly affordable coverage, society must be able to contain the overall cost of health care, and health insurance must be progressively financed, meaning that those who are best able to pay for coverage should pay the largest share. While the recently passed Patient Protection and Affordable Care Act (ACA) falls short on both of these counts, we argue that it makes important contributions toward household affordability through the use of subsidies and regulations. The main shortcoming of the ACA is an insufficient protection against burdensome cost sharing, which we illustrate using several hypothetical scenarios. We conclude with recommendations about how to make opportunity-enhancing expansions to the current coverage subsidies. PMID- 22065689 TI - Cyclo-linopeptide K butanol disolvate monohydrate. AB - The title compound, C(56)H(83)N(9)O(11)S.2C(4)H(10)O.H(2)O, is a butanol-water solvate of the cyclo-linopeptide cyclo(Metsulfone(1)-Leu(2)-Ile(3)-Pro(4)-Pro(5) Phe(6)-Phe(7)-Val(8)-Ile(9)) (henceforth referred to as CLP-K) which was isolated from flax oil. All the amino acid residues are in an l configuration based on the CORN rule. The cyclic nona-peptide exhibits eight trans peptide bonds and one cis peptide bond observed between the two proline residues. The conformation is stabilized by an alpha- and a beta-turn, each containing an N-H?O hydrogen bond between the carbonyl group O atom of the first residue and the amide group H atom of the fourth (alpha-turn) and the third residue (beta-turn), repectively. In the crystal, the components of the structure are linked by inter-molecular N-H?O and O-H?O hydrogen bonds into a two-dimensional network parallel to (001). The C(H(2))OH group of one of the butanol solvent mol-ecules is disordered over two sets of sites with refined occupancies of 0.863 (4) and 0.137 (4). PMID- 22065690 TI - Neurological biomarkers in the perioperative period. AB - The rapid detection and evaluation of patients presenting with perioperative neurological dysfunction is of great clinical relevance. Biomarkers have been defined as biological molecules that can be used as an indicator of new onset or progression of a biological process or effect of treatment. Biomarkers have become increasingly important in this setting to supplement other modalities of diagnosis such as EEG, sensory- or motor-evoked potential, transcranial Doppler, near-infrared spectroscopy, or imaging methods. A number of neuro-proteins have been identified and are currently under investigation for potential to provide insights into injury severity, outcome, and the ability to monitor cellular damage and molecular events that occur during neurological injury. S100B is a protein released by glial cells and is considered a marker of blood-brain barrier dysfunction. Clinical studies in patients undergoing cardiac and non-cardiac surgery indicate that serum levels of S100B are increased intraoperatively and after operation. The neurone-specific enolase has also been extensively investigated as a potential marker of neuronal injury in the context of cardiac and non-cardiac surgery. A third biomarker of interest is the Tau protein, which has been linked to neurodegenerative disorders. Tau appears to be more specific than the previous two biomarkers since it is only found in the central nervous system. The metalloproteinase and ubiquitin C terminal hydroxylase-L1 (UCH-L1) are the most recently researched markers; however, their usefulness is still unclear. This review presents a comprehensive overview of S100B, neuronal specific enolase, metalloproteinases, and UCH-L1 in the perioperative period. PMID- 22065691 TI - Brain-penetrating IgG-iduronate 2-sulfatase fusion protein for the mouse. AB - Mucopolysaccharidosis (MPS) type II (Hunter's syndrome) is caused by mutations in the iduronate 2-sulfatase (IDS) fusion protein. MPS-II affects the brain, and enzyme replacement therapy is not effective in the brain, because the enzyme does not cross the blood-brain barrier. To treat mouse models of MPS-II with brain penetrating IDS, the lysosomal enzyme was reengineered as an IgG-IDS fusion protein. The mature human IDS was fused to the carboxyl terminus of both heavy chains of the chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), and the fusion protein is designated cTfRMAb-IDS. The purity and identity of the fusion protein was confirmed by electrophoresis and Western blotting with antibodies to mouse IgG and human IDS. The EC50 of binding of the cTfRMAb-IDS fusion protein to the mouse TfR (0.85 +/- 0.15 nM) was comparable to the EC50 of binding of the cTfRMAb (0.78 +/- 0.05 nM). The IDS enzyme activity of the cTfRMAb-IDS fusion protein was 126 +/- 1 nmol . h-1 . MUg-1 protein. After intravenous injection in the mouse, the cTfRMAb-IDS fusion protein was rapidly removed from plasma and distributed to tissues, including brain and spinal cord. The uptake of the fusion protein by brain or spinal cord was 1.3 +/- 0.1 and 2.2 +/- 0.2% injected dose/g, respectively, which is 100-fold greater than the brain uptake of IDS alone. This work shows that a lysosomal sulfatase can be reengineered as an IgG-enzyme fusion protein that rapidly penetrates the brain after intravenous administration. PMID- 22065692 TI - Poly[(5,5'-dimethyl-2,2'-bipyridine-kappaN,N')(MU(3)-5-hy-droxy-isophthalato kappaO:O,O:O)cadmium]. AB - In the title compound, [Cd(C(8)H(4)O(5))(C(12)H(12)N(2))], the Cd(II) cation is coordinated by three 5-hy-droxy-isophthalate anions and one 5,5'-bimethyl-2,2' bipyridine ligand in a distorted CdO(4)N(2) octa-hedral geometry. The 5-hy-droxy isophthalate anions bridge the Cd cations, forming a two-dimensional polymeric complex parallel to (100). In the complex, the hy-droxy group is linked to the uncoordinated carb-oxy-O atom via an O-H?O hydrogen bond. Weak C-H?O hydrogen bonds are also present in the crystal structure. One of the methyl groups is disordered over two positions in a 0.536 (11):0.464 (11) ratio. PMID- 22065693 TI - Hexa-MU-chlorido-MU(4)-oxido-tetra-kis-({1-[(pyridin-2-yl)meth-yl]-1H benzimidazole-kappaN}copper(II)). AB - The title tetra-nuclear complex, [Cu(4)Cl(6)O(C(13)H(11)N(3))(4)], features a tetra-hedral arrangement of copper(II) ions bonded to the central O atom (site symmetry [Formula: see text]). Each of the six edges of the Cu(4) tetra-hedron is bridged by a chloride ion (one of which has site symmetry 2), so that each copper ion is linked to the other three metal ions through the central O atom and through three separate chloride-ion bridges. The fifth coord-ination position, located on the central Cu-O axis on the outside of the cluster, is occupied by an N atom of the mono-dentate 1-(pyridin-2-ylmeth-yl)-1H-benzimidazole ligand. The resulting coordination geometry of the metal ion is a distorted trigonal bipyramid with the O and N atoms in the axial positions. The dihedral angle between the benzimidazole ring system and the pendant pyridine ring is 61.0 (2) degrees . PMID- 22065694 TI - 3-Hy-droxy-2-(hy-droxy-meth-yl)pyridinium chloride. AB - The cation of the title compound, C(6)H(8)NO(2) (+).Cl(-), is essentially planar (r.m.s. deviation = 0.0104 A). Intermolecular O-H?Cl and N-H?Cl hydrogen bonds, as well as C-H?O contacts, connect the mol-ecules in the crystal structure. A short C?C distance of only 3.3930 (19) A between C atoms of neighbouring rings is indicative of pi-stacking. The corresponding centroid-centroid distance between the two aromatic systems is 4.2370 (7) A due to the small overlap of the adjacent rings. PMID- 22065695 TI - 2,6,6-Trimethyl-cyclo-hexene-1-carbaldehyde oxime. AB - In the crystal of the title compound C(10)H(17)NO, synthesized by the reaction of beta-cyclo-citral with hydroxyl-amine hydro-chloride, inversion-related mol ecules are linked by a pair of O-H?N hydrogen-bonding inter-actions between the oxime functionalities, forming R(2) (2)(6) loops. The molecular conformation is stabilized by intra-molecular methyl C-H?N inter-actions. The cyclohexene ring has the typical half-chair conformation. PMID- 22065696 TI - Piperazine-1,4-diium naphthalene-1,5-disulfonate. AB - The title molecular salt, C(4)H(12)N(2) (2+).C(10)H(6)O(6)S(2) (2-), consists of a piperazinium cation and a 1,5-naphthalene-disulfonate anion. Crystallographic inversion centers are situated at the center of the ring of the dication as well as at the midpoint of the central carbon-carbon bond in the dianion. In the crystal, inter-molecular N-H?O hydrogen bonds link the cations and anions. PMID- 22065697 TI - Tris(1,10-phenanthroline)iron(II) MU-oxido-bis-[trichloridoferrate(III)]. AB - In the title salt, [Fe(C(12)H(8)N(2))(3)][Fe(2)Cl(6)O], the ionic components are linked into a two-dimensional supra-molecular layer by two pairs of C-H?Cl hydrogen bonds and pi-pi stacking inter-actions [centroid-centroid distances = 3.655 (4) and 3.498 (3) A]. The salt is characterized as a mixed-valent Fe(II) Fe(III) compound, in which an Fe(II) atom is coordinated by three phen ligands, forming a six-coordinated cationic entity and the anionic part is formed by two Fe(III) atoms in tetra-hedral coordination environments constructed by three chloride ions and one bridging oxide ligand. Intra-molecular C-H?N hydrogen bonds are observed. PMID- 22065698 TI - [3-Chloro-N'-(2-oxidonaphthalen-1-yl methylidene)benzohydrazidato]methanol(methanolato)oxidovanadium(V). AB - In the title complex, [V(C(18)H(11)ClN(2)O(2))(CH(3)O)O(CH(3)OH)], the V(V) ion is coordinated by a tridendate 3-chloro-N'-(2-oxidonaphthalen-1 ylmethylidene)benzohydrazidate ligand, one oxido ligand and by O atoms from a methanol and a methoxide ligand, forming a distorted octa-hedral geometry. The dihedral angle between the benzene ring and the naphthyl-ene ring system is 6.4 (3) degrees . The deviation of the V(V) ion from the plane defined by the three donor atoms of the tridentate ligand and the meth-oxy O atom towards the oxido O atom is 0.323 (2) A. In the crystal, pairs of inter-molecular O-H?N hydrogen bonds form centrosymmetric dimers. PMID- 22065699 TI - 2-[4-(2-Formyl-phen-oxy)-but-oxy]-benzaldehyde. AB - In the crystal structure of the title compound, C(18)H(18)O(4), the full mol ecule is generated by the application of an inversion centre. The mol-ecule is essentially planar, with an r.m.s. deviation of 0.017 (1) A for all non-H atoms. The mol-ecules are linked through inter-molecular C-H?O inter-actions to form a mol-ecular sheet parallel to the ([Formula: see text]02) plane. PMID- 22065700 TI - Bis(hydrogen l-glutamato)palladium(II). AB - In the title compound, [Pd(C(5)H(8)NO(4))(2)], the Pd(II) atom is coordinated by two O atoms and two N atoms of two N,O-chelating hydrogen l-glutatmate ligands in a square-planar geometry with the N and O atoms in a mutually trans arrangement. The complex units are embedded in a network of N-H?O and O-H?O hydrogen-bonding inter-actions that stabilize the three-dimensional crystal structure. The strongest hydrogen bonds are formed between the gamma-COOH untis of adjacent glutamate ligands, leading to dimers of the type R(2) (2)(8) with O?O separations of 2.640 (6) A. PMID- 22065701 TI - The mixed-valent titanium phosphate, Li(2)Ti(2)(PO(4))(3), dilithium dititanium(III/IV) tris-(orthophosphate). AB - The mixed-valent titanium phosphate, Li(2)Ti(2)(PO(4))(3), has been prepared by the reactive halide flux method. The title compound is isostructural with Li(2)TiM(PO(4))(3) (M = Fe, Cr) and Li(2)FeZr(PO(4))(3) and has the same (3) (infinity)[Ti(2)(PO(4))(3)](2-) framework as the previously reported Li(3-) (x)M(2)(PO(4))(3) phases. The framework is built up from corner-sharing TiO(6) octa-hedra and PO(4) tetra-hedra, one of which has 2 symmetry. The Li(+) ions are located on one crystallographic position and reside in the vacancies of the framework. They are surrounded by four O atoms in a distorted tetra-hedral coordination. The classical charge-balance of the title compound can be represented as Li(+) (2)(Ti(3+)/Ti(4+))(PO(4) (3-))(3). PMID- 22065702 TI - trans-Carbonyl-chloridobis[tris(naph-thalen-1-yl)-phosphane-kappaP]rhodium(I) acetone trisolvate. AB - In the title compound, trans-[RhCl{P(C(10)H(7))(3)}(2)(CO)].3C(3)H(6)O, where P(C(10)H(7))(3) is trinaphthyl-phosphine, the Rh-P bond lengths are 2.3360 (10) and 2.3258 (10) A, while the Rh-Cl bond length is 2.3525 (11) A. The coordination around the Rh atom shows a slightly distorted square-planar arrangement. PMID- 22065703 TI - Sociocultural beliefs and treatment acceptance. AB - The beliefs of patients attending walk-in clinic and outpatient section, Department of Psychiatry, NIMHANS, Bangalore were studied separately. The Walk-in Clinic and Outpatient population were divided into three groups by systematic randomization. The beliefs of Group I, Hand III were left untouched, contradicted and supported respectively. The follow up attendance pattern of the patients was taken as an indicator of treatment acceptance and according to the regularity of follow up in each group patients were categorised as good, fair and poor attenders.The significance of these findings is discussed and it is inferred that supporting scientifically tenable beliefs and keeping a neutral attitude towards unscientific beliefs may be the best policy for a clinician. PMID- 22065704 TI - catena-Poly[[[bis-(3-amino-pyrazine-2-carboxyl-ato)triaqua-praseodymium(III)]-MU 3-amino-pyrazine-2-carboxyl-ato-[(3-amino-pyrazine-2-carboxyl-ato)diaqua formatopraseodymium(III)]-MU-3-amino-pyrazine-2-carboxyl-ato] hexa-hydrate]. AB - The asymmetric unit of the polymeric title compound, {[Pr(2)(C(5)H(4)N(3)O(2))(5)(CHO(2))(H(2)O)(5)].6H(2)O}(n), has two independent Pr(III) atoms; one is coordinated by two water mol-ecules and the other by three water mol-ecules. The first is N,O-chelated by three 3-amino-pyrazine-2-carboxyl ate ions, whereas the second is chelated by two carboxyl-ate ions; both exist in a monocapped square-anti-prismatic geometry. The polymeric chains that run along the a axis inter-act with the lattice water mol-ecules, generating a three dimensional hydrogen-bonded network. The formate ion is disordered over two positions with respect to the non-coordinated atoms in a 1:1 ratio. PMID- 22065705 TI - Chlorido(10,11,12,13-tetra-hydro-4,5,9,14-tetra-aza-benzo[b]triphenyl-ene kappaN,N)copper(I). AB - The Cu(I) atom in the title compound, [CuCl(C(18)H(14)N(4))], is N,N'-chelated by the N-heterocyclic ligand and coordinated by one Cl(-) anion in a distorted trigonal geometry. In the crystal, the Cu(I) atom is disordered over two positions in a 0.667 (6):0.333 (6) ratio. The deviation of the Cu atom from the N/N/Cl coordination plane is 0.013 (3) A for the major component and 0.073 (6) A for the minor component. Two methyl-ene C atoms are also disordered over two positions in a 0.667 (6):0.333 (6) ratio. PMID- 22065706 TI - [(E)-10-(2,6-Dimethyl-phenyl-imino)-9-methyl-9,10-dihydro-phenanthren-9 olato]penta-methyl-dialuminum(III). AB - The two Al atoms in the title compound, [Al(2)(CH(3))(5)(C(23)H(20)NO)], are four coordinated in a distorted tetra-hedral environment. The coordination of one Al atom includes three methyl-C atoms and the O atom from the ligand, whereas the second Al atom is surrounded by the O atom and one N atom from the ligand as well as by two methyl-C atoms. In the ligand, the dihedral angle between the two phenyl rings in the 9,10-dihydro-phenanthren unit is 20.64 (12) degrees . PMID- 22065707 TI - Evaluation of a method for assessing pulmonary function in laryngectomees. AB - In total laryngectomies the impairment of pulmonary function reflects the sum of pre- and post-operative ventilatory changes. Objective information on the respiratory condition in laryngectomees, as assessed in the pulmonary function laboratory is somewhat limited, perhaps because of difficulties related to methodology. The aim of our study was to evaluate the reproducibility of a method employed to assess the pulmonary function in laryngectomized patients. The experimental extra-tracheal device was set up with a silicone adapter through a cardboard tube to the skin around the tracheostoma. Pulmonary function tests included measurements of forced vital capacity, force expiratory volume at 1 second and Tiffeneau index in 3 consecutive evaluations, in 11 patients who underwent total laryngectomy. The control group comprised 11 patients, not laryngectomized, evaluated by conventional spirometry. Those responsible for evaluating were asked to report possible technical failures and to demonstrate the reproducibility of the curves resulting from the tests. The use of the silicone adapter and skin adhesive provided a complete, airtight seal of the system, in all cases. The presence of the tracheo-oesophageal prosthesis did not negatively affect the test results. All patients attributed a maximum value, both for comfort and acceptance, of the device. The values are comparable in both groups, thus indicating the accuracy of the proposed methodology. All examinations were reproducible. After total laryngectomy, pulmonary function testing, with an extra-tracheal device, is not only reliable but also easy to perform in a routine out-patient setting. The methodology did not present air leaks and was, therefore, well accepted by all patients tested. PMID- 22065708 TI - N-(2-Chloro-phen-yl)-N'-(2-methyl-phen-yl)succinamide. AB - In the title compound, C(17)H(17)ClN(2)O(2), the asymmetric unit contains half a mol-ecule with a centre of symmetry at the mid-point of the central C-C bond. The conformations of the amide O atoms are anti to the methyl-ene atoms. Further, the N-H bonds in the amide fragments are anti to the ortho-chloro/methyl groups in the adjacent benzene rings. The dihedral angle between the benzene ring and the NH-C(O)-CH(2) segment in the two halves of the mol-ecule is 62.0 (2) degrees . In the crystal, a series of N-H?O inter-molecular hydrogen bonds link the mol-ecules into column-like infinite chains along the a axis. The methyl and Cl groups are disordered with respect to the ortho positions of the benzene ring, with site occupation factors of 0.5 each. PMID- 22065709 TI - Nuclear detonation and infertility: Evidence. PMID- 22065710 TI - 4-(4-Bromo-phen-yl)-2,3,3a,4,5,11c-hexa-hydro-benzo[f]furo[3,2-c]quinoline. AB - In the title compound, C(21)H(18)BrNO, both heterocyclic rings, viz. the hydro pyridine ring and the adjacent hydro-furan ring, adopt envelope conformations. These two heterocycles make a dihedral angle of 37.3 (1) degrees . The dihedral angle between the hydro-pyridine and benzene rings is 69.6 (1) degrees . In the crystal, adjacent mol-ecules are linked by pairs of inter-molecular C-H?O hydrogen bonds, forming centrosymmetric dimers. PMID- 22065711 TI - Dicaesium diaqua-bis-(methyl-ene-diphospho-nato-kappaO,O')cobaltate(II). AB - The asymmetric unit of the title compound, Cs(2)[Co(CH(4)O(6)P(2))(2)(H(2)O)(2)], is comprised of one bidentate methyl-enediphospho-nate ligand and one water mol ecule which are coordinated to the Co(II) atom, as well as a caesium counter cation. The Co atom occupies a special position on a crystallographic inversion center. The caesium ion is octa-hedrally coordinated by six O atoms with Cs-O distances ranging from 3.119 (2) to 3.296 (2) A. A three-dimensional network is formed through O-H?O hydrogen bonds. PMID- 22065712 TI - 2,2'-(1,3-Diazinane-1,3-di-yl)diaceto-nitrile: a second monoclinic polymorph. AB - A new monoclinic polymorph of the title compound, C(8)H(12)N(4), in the space group P2(1)/n (Z = 4) is reported. The previously known form was also monoclinic, P2(1)/c (Z = 4), but the unit-cell parameters and crystal packing were different [Shoja & Saba (1993 ?). Acta Cryst. C49, 354-355]. The hexa-hydro-pyrimidine ring of the title compound adopts a chair conformation with a diequatorial substitution and with the CH(2)-C N groups oriented nearly parallel and in the same direction [NC-CH(2)?CH(2)-CN pseudo torsion angle = -6.27 (18) degrees ]. In the crystal, inter-molecular C-H? N hydrogen bonds connects the mol-ecules into a chain along the b axis. PMID- 22065713 TI - {4-[(2,4-Dichloro-benzo-yloxy)meth-yl]-1-phenyl-1H-1,2,3-triazol-5-yl}methyl 2,4 dichloro-benzoate. AB - In the title molecule, C(24)H(15)Cl(4)N(3)O(4), the triazole ring makes dihedral angles of 72.02 (12), 81.60 (12) and 73.82 (11) degrees , respectively, with the adjacent phenyl ring and the two dichloro-benzene rings. In the crystal, a weak C H?N inter-action, a short Cl?Cl contact [3.307 (2) A] and a pi-pi stacking inter action [centroid-centroid distance = 3.568 (4) A] are observed. An intra molecular C-H?O inter-action is also present. PMID- 22065714 TI - 2-(3H-1,3-Benzothia-zol-2-yl-idene)-propane-dial. AB - In the title compound, C(10)H(7)NO(2)S, the dihedral angle between the benzimidazole and malonaldehyde group is 1.41 (2) degrees . An intra-molecular hydrogen bond is formed between the NH group and one of the adjacent carbonyl O atoms. In addition, the NH group forms an inter-molecular hydrogen bond to a symmetry equivalent of this carbonyl O atom, connecting the mol-ecules into centrosymmetric dimers. The structure also contains C-H?O inter-molecular inter actions. PMID- 22065715 TI - (2-Benzoyl-phen-yl)(2-meth-oxy-1-naphth-yl)methanone. AB - In the title compound C(25)H(18)O(3), the central benzene ring forms dihedral angles of 87.4 (5) and 85.4 (4) degrees with the phenyl ring and the naphthalene ring system, respectively. The carbonyl O atoms deviate significantly from the phenyl ring and the meth-oxy-substituted naphthalene ring system [by 0.508 (1) and 0.821 (1) A, respectively]. The crystal packing is stabilized by C-H?O hydrogen bonds, which generate C(6) chains, and C-H?pi inter-actions. PMID- 22065716 TI - 1-Azido-N'-(phenylsulfonyl)methan-imid-amide. AB - In the title compound, C(7)H(7)N(5)O(2)S, the aromatic ring is oriented at dihedral angles of 79.46 (2) and 89.17 (2) degrees , respectively, with respect to the amino-(azido)-methyl and the S(6) six-membered ring motif generated by an intra-molecular N-H?O inter-action [N?O = 2.8901 (15) A]. Inter-molecular N-H?O hydrogen bonds [N?O = 2.9177 (15) and 2.9757 (15) A] generate an infinite one dimensional network along the base vector (010). PMID- 22065717 TI - (2,4-Dihy-droxy-6-meth-oxy-phen-yl)(3,5-dihy-droxy-phen-yl)methanone monohydrate. AB - The title benzophenone compound, C(14)H(12)O(6).H(2)O, was isolated from the bark of Garcinia hombroniana Pierre (Guttiferae). The mol-ecule is twisted, the dihedral angle between the two benzene rings being 59.13 (7) degrees . The meth oxy group is approximately coplanar with the attached benzene ring, with a C-O-C C torsion angle of 1.91 (18) degrees . The water mol-ecule is disordered over two positions in a 0.555 (19):0.445 (19) ratio. An intra-molecular O-H?O hydrogen bond generates an S(6) ring motif. The crystal structure is stabilized by inter molecular O-H?O hydrogen bonds. These inter-actions link the mol-ecules into sheets parallel to the ac plane. The sheets are stacked along the b axis by pi-pi inter-actions, with centroid-centroid distances of 3.6219 (7) A. A weak O-H?pi inter-action was also noted. PMID- 22065718 TI - {meso-Tetra-kis[p-(hept-yloxy)phen-yl]-porphyrinato}silver(II). AB - The title compound, [Ag(C(72)H(84)N(4)O(4))], crystallizes with the Ag(II) cation on a centre of symmetry. The macrocyclic 24-membered ring core is planar with a mean deviation of 0.0311 (15) A and the four-coordinate Ag(II) cation fits into its center, at 2.0814 (19) and 2.0872 (19) A, from the surrounding pyrrole-N atoms, in agreement with what is found in related compounds. The p-heptyl oxyphenyl groups are rotated 75.51 (5) and 84.45 (8) degrees with respect to the porphyrin mean plane, due to steric hindrance with the pyrrole-H atoms of the macrocycle. PMID- 22065719 TI - N-Benzyl-5-(dimethyl-amino)-naphthalene-1-sulfonamide. AB - The structure of the title compound, C(19)H(20)N(2)O(2)S, displays inter molecular N-H?O hydrogen bonding, which generates inversion dimers. There is no pi-pi stacking in the crystal structure. The dihedral angle between the phenyl ring and naphthalene ring system is 59.16 (11) degrees . PMID- 22065720 TI - Activated STAT5 promotes long-lived cytotoxic CD8+ T cells that induce regression of autochthonous melanoma. AB - Immunotherapy based on adoptive transfer of tumor antigen-specific CD8(+) T cell (TC) is generally limited by poor in vivo expansion and tumor infiltration. In this study, we report that activated STAT5 transcription factors (STAT5CA) confer high efficiency on CD8(+) effector T cells (eTC) for host colonization after adoptive transfer. Engineered expression of STAT5CA in antigen-experienced TCs with poor replicative potential was also sufficient to convert them into long lived antigen-responsive eTCs. In transplanted mastocytoma- or melanoma-bearing hosts, STAT5CA greatly enhanced the ability of eTCs to accumulate in tumors, become activated by tumor antigens, and to express the cytolytic factor granzyme B. Taken together, these properties contributed to an increase in tumor regression by STAT5CA-transduced, as compared with untransduced, TCs including when the latter control cells were combined with infusion of interleukin (IL) 2/anti-IL-2 complexes. In tumors arising in the autochthonous TiRP transgenic model of melanoma associated with systemic chronic inflammation, endogenous CD8(+) TCs were nonfunctional. In this setting, adoptive transfer of STAT5CA transduced TCs produced superior antitumor effects compared with nontransduced TCs. Our findings imply that STAT5CA expression can render TCs resistant to the immunosuppressive environment of melanoma tumors, enhancing their ability to home to tumors and to maintain high granzyme B expression, as well as their capacity to stimulate granzyme B expression in endogenous TCs. PMID- 22065721 TI - Use of multifunctional sigma-2 receptor ligand conjugates to trigger cancer selective cell death signaling. AB - One major challenge in the development of cancer therapeutics is the selective delivery of the drugs to their cellular targets. In the case of pancreatic cancer, the sigma-2 receptor is a unique target that triggers apoptosis upon activation. We have previously developed a series of chemical compounds with high affinity for the sigma-2 receptor and showed rapid internalization of the ligands. One particular specific ligand of the sigma-2 receptor, SV119, binds to pancreatic cancer cells and induces target cell death in vitro and in vivo. In this study, we characterized the ability of SV119 to selectively deliver other death-inducing cargos to augment the cytotoxic properties of SV119 itself. When conjugated to SV119, small molecules that are known to interfere with intracellular prosurvival pathways retained their ability to induce cell death, the efficiency of which was enhanced by the combinatorial effect of SV119 delivered with its small molecule cargo. Our findings define a simple platform technology to increase the tumor-selective delivery of small molecule therapeutics via sigma-2 ligands, permitting chemotherapeutic synergy that can optimize efficacy and patient benefit. PMID- 22065722 TI - A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment. AB - Constitutive production of inflammatory cytokines is a characteristic of many human malignant cell lines; however, the in vitro and in vivo interdependence of these cytokines, and their significance to the human cancer microenvironment, are both poorly understood. Here, we describe for the first time how three key cytokine/chemokine mediators of cancer-related inflammation, TNF, CXCL12, and interleukin 6, are involved in an autocrine cytokine network, the "TNF network," in human ovarian cancer. We show that this network has paracrine actions on angiogenesis, infiltration of myeloid cells, and NOTCH signaling in both murine xenografts and human ovarian tumor biopsies. Neutralizing antibodies or siRNA to individual members of this TNF network reduced angiogenesis, myeloid cell infiltration, and experimental peritoneal ovarian tumor growth. The dependency of network genes on TNF was shown by their downregulation in tumor cells from patients with advanced ovarian cancer following the infusion of anti-TNF antibodies. Together, the findings define a network of inflammatory cytokine interactions that are crucial to tumor growth and validate this network as a key therapeutic target in ovarian cancer. PMID- 22065723 TI - Dichloridotetra-kis-(diniconazole)cobalt(II). AB - In the crystal structure of the title compound, [CoCl(2)(C(15)H(17)Cl(2)N(3)O)(4)], the Co(II) cation lies on an inversion center and has a slightly distorted octa-hedral coordination geometry. The equatorial positions are occupied by four N atoms from four diniconazole [systematic name: (E)-(RS)-1-(2,4-dichloro-phen-yl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pent-1-en 3-ol] ligands. The axial sites are occupied by two Cl(-) anions. In the two independent organic ligands, the triazole ring is oriented at dihedral angles of 18.28 (14) and 32.15 (14) degrees with respect to the dichloro-phenyl ring. Inter-molecular O-H?Cl hydrogen bonds consolidate the crystal packing. PMID- 22065724 TI - 2-(1,3-Benzoxazol-2-yl)-1-phenyl-ethenyl benzoate. AB - In the title mol-ecule, C(22)H(15)NO(3), the configuration about the ethyl-enic double bond is Z configuration and it is approximately coplanar with the adjacent phenyl ring and benzoxazole ring system as indicated by the C(H)=C(O)-C(phen-yl) C(phen-yl) and O(benzoxazole)-C-C(H)=C(O) torsion angles of 179.88 (15) and 5.7 (2) degrees , respectively. The dihedral angle between the essentially planar (r.m.s. deviation = 0.080 A) 2-(1,3-benzoxazol-2-yl)-1-phenyl-ethenyl group and the benzoate phenyl ring is 61.51 (6) degrees . A short intra-molecular O?O non bonded inter-action of 2.651 (2) A is present. PMID- 22065725 TI - Cyclo-hex-yl(meth-yl)ammonium {bis-[cyclo-hex-yl(meth-yl)amino]-phosphor-yl}(4 methyl-phenyl-sulfon-yl)aza-nide. AB - In the anion of the title salt, C(7)H(16)N(+).C(21)H(35)N(3)O(3)PS(-), the P and S atoms are both in distorted tetra-hedral environments and the angles at the tertiary N atoms confirm their sp(2) character. The two S=O groups are in syn and gauche conformations with respect to the phosphoryl group. In the crystal, N H?O(=S) and N-H?O(=P) hydrogen bonds involving two anions and two cations form a centrosymmetric four-component cluster. PMID- 22065726 TI - 5-(Biphenyl-4-yl)-3-(3-meth-oxy-benzyl-idene)furan-2(3H)-one. AB - In the title compound, C(24)H(18)O(3), the dihedral angles between the mean planes of the five-membered furan ring and the meth-oxy-substituted benzene and the adjacent and outer biphenyl benzene rings are 2.43 (7), 4.48 (7) and 30.47 (8) degrees , respectively. The crystal packing is stabilized by weak C-H?O and C H?pi inter-molecular hydrogen bonds and pi-pi stacking inter-actions [centroid centroid distances = 3.8752 (8) and 3.8331 (8) A]. PMID- 22065727 TI - A clinical and follow up study of atypical psychoses. AB - Twenty-two cases who fulfilled the criteria of having atypical manifestation at any stage of illness and had minimum follow up of three years were studied in detail. Their family history and follow up was analysed. The findings of the present study suggest that the cases showing admixture of schizophrenic and affective symptoms are probably a variant of affective disorders although a possibility of their being a third independent psychosis cannot be ruled out. PMID- 22065728 TI - 3,4,5-Trihy-droxy-benzohydrazide. AB - In the title compound, C(7)H(8)N(2)O(4), the dihedral angle between the aromatic ring and the hydrazide grouping is 21.34 (7) degrees . In the crystal, the mol ecules are linked into a three-dimensional network by O-H?O, O-H?N and N-H?O hydrogen bonds. PMID- 22065729 TI - 6-Methyl-nicotinic acid. AB - All non-H atoms of the title compound, C(7)H(7)NO(2), are nearly coplaner, the r.m.s. deviation being 0.0087 A. In the crystal, the partially overlapped arrangement and the face-to-face distance of 3.466 (17) A between parallel pyridine rings of neighboring mol-ecules indicates the existence of pi-pi stacking. Inter-molecular O-H?N hydrogen bonding and weak C-H?O hydrogen bonding are present in the crystal structure. PMID- 22065730 TI - Cerebral abscess following adenotonsillectomy: a rare complication. AB - In the present paper, we report an extremely rare case of a 4-year-old girl who developed a frontal lobe intracerebral abscess following adenotonsillectomy. This was diagnosed by computerised tomography at scan 21 days post-tonsillectomy when she presented with bilateral sixth nerve palsies. We believe that intracranial complications should be considered in any patient who present with headache or vomiting following tonsil surgery, especially if the patient has a spiking pyrexia. PMID- 22065731 TI - N'-[(1E)-(2-Hy-droxy-naphthalen-1-yl)methyl-idene]-2-meth-oxy-benzohydrazide. AB - There are three independent mol-ecules in the asymmetric unit of the title compound, C(19)H(16)N(2)O(3), in which the dihedral angles between the naphthalene ring system and the benzene ring are 7.52 (16), 18.15 (18), and 13.9 (2) degrees . All the mol-ecules exist in the trans configuration with respect to the methyl-idene units. In each mol-ecule there is one O-H?N and one N-H?O intra molecular hydrogen bond. In the crystal, two of the mol-ecules are linked via a bifurcated N-H?(O,O) hydrogen bond. All three mol-ecules are further linked via C H?O inter-actions. PMID- 22065732 TI - Leptin promotes the mobilization of vascular progenitor cells and neovascularization by NOX2-mediated activation of MMP9. AB - AIMS: Bone marrow (BM) progenitors participate in new vessel formation and endothelial repair. The leptin receptor (ObR) is expressed on hematopoietic cells; however, the effects of leptin on BM progenitor cells and their angiogenic potential are unknown. METHODS AND RESULTS: In the present study, we show that the short-term administration of leptin (over five consecutive days) into wild type mice increased the number of circulating, BM-derived sca-1(+), flk-1(+) vascular progenitors, 95 +/- 1.7% of which also expressed ObR. Ex vivo stimulation of BM cells with leptin enhanced the expression of NADPH oxidase isoform 2 (NOX2), and the leptin-induced increase in reactive oxygen species production, matrix metalloproteinase-9 (MMP9) expression and circulating soluble KitL levels was absent in mice lacking NOX2. Furthermore, intraperitoneal injections of leptin improved perfusion and increased the number of BM-derived, CD31-positive endothelial cells in ischaemic hindlimbs after femoral artery ligation. The effects of leptin on the mobilization of sca-1(+), flk-1(+) cells and neovascularization were abolished in mice transplanted with BM from ObR deficient and in NOX2(-/-) mice. CONCLUSION: Our findings suggest that the angiogenic effects of leptin involve sca-1(+), flk-1(+) vascular progenitor cells mobilized from the BM in response to ObR-mediated activation of NOX2, increased MMP9 expression, and sKitL release. PMID- 22065733 TI - MicroRNA and vascular remodelling in acute vascular injury and pulmonary vascular remodelling. AB - Vascular remodelling is an integral pathological process central to a number of cardiovascular diseases. The complex interplay between distinct cell populations in the vessel wall following vascular injury leads to inflammation, cellular dysfunction, pro-growth signals in the smooth muscle cell (SMC) compartment, and the acquisition of a synthetic phenotype. Although the signals for vascular remodelling are diverse in different pathological contexts, SMC proliferation and migration are consistently observed. It is therefore critical to elucidate key mechanisms central to these processes. MicroRNAs (miRNAs) are small non-coding sequences of RNA that have the capacity to regulate many genes, pathways, and complex biological networks within cells, acting either alone or in concert with one another. In diseases such as cancer and cardiac disease, the role of miRNA in disease pathogenesis has been documented in detail. In contrast, despite a great deal of interest in miRNA, relatively few studies have directly assessed the role of miRNA in vascular remodelling. The potential for modulation of miRNA to achieve therapeutic benefits in this setting is attractive. Here, we focus on the role of miRNA in vascular inflammation and remodelling associated with acute vascular injury (vein graft disease, angioplasty restenosis, and in-stent restenosis) as well as in vascular remodelling associated with the development of pulmonary arterial hypertension. PMID- 22065735 TI - Bromocriptine or cabergoline-induced cerebrospinal fluid rhinorrhea: A life threatening complication during management of prolactinoma. PMID- 22065734 TI - Role of microRNAs in diabetes and its cardiovascular complications. AB - Diabetes is the most common metabolic disorder and is recognized as one of the most important health threats of our time. MicroRNAs (miRNAs) are a novel group of non-coding small RNAs that have been implicated in a variety of physiological processes, including glucose homeostasis. Recent research has suggested that miRNAs play a critical role in the pathogenesis of diabetes and its related cardiovascular complications. This review focuses on the aberrant expression of miRNAs in diabetes and examines their role in the pathogenesis of endothelial dysfunction, cardiovascular disease, and diabetic retinopathy. Furthermore, we discuss the potential role of miRNAs as blood biomarkers and examine the potential of therapeutic interventions targeting miRNAs in diabetes. PMID- 22065736 TI - N-(Prop-2-yn-1-yl)-1,3-benzothia-zol-2-amine. AB - In the title compound, C(10)H(8)N(2)S, the 2-amino-benzothia-zole and propyne groups are not coplanar [dihedral angle = 71.51 (1) degrees ]. The crystal structure is stabilized by strong inter-molecular N-H?N hydrogen bonds and C-H?C, C-H?pi and F-type aromatic-aromatic [centroid-centroid distance = 3.7826 (12) A] inter-actions are also observed. PMID- 22065737 TI - Glycogen synthase kinase (GSK)-3 promotes p70 ribosomal protein S6 kinase (p70S6K) activity and cell proliferation. AB - The p70 ribosomal protein S6 kinase 1 (S6K1) plays a key role in cell growth and proliferation by regulating insulin sensitivity, metabolism, protein synthesis, and cell cycle. Thus, deregulation of S6K contributes to the progression of type 2 diabetes, obesity, aging, and cancer. Considering the biological and clinical importance of S6K1, a complete understanding of its regulation is critical. One of the key motifs in the activation of S6K1 is a turn motif, but its regulation is not well understood. Here we provide evidence for two mechanisms of modulating turn motif phosphorylation and S6K1 activity. First, mammalian target of rapamycin regulates turn motif phosphorylation by inhibiting its dephosphorylation. Second, we unexpectedly found that glycogen synthase kinase (GSK)-3 promotes turn motif phosphorylation. Our studies show that mammalian target of rapamycin and GSK-3 cooperate to control the activity of S6K1, an important regulator of cell proliferation and growth. Our unexpected results provide a clear rationale for the development and use of drugs targeting GSK-3 to treat diseases such as diabetes, cancer, and age-related diseases that are linked to improper regulation of S6K1. PMID- 22065738 TI - Impaired lymphatic contraction associated with immunosuppression. AB - To trigger an effective immune response, antigen and antigen-presenting cells travel to the lymph nodes via collecting lymphatic vessels. However, our understanding of the regulation of collecting lymphatic vessel function and lymph transport is limited. To dissect the molecular control of lymphatic function, we developed a unique mouse model that allows intravital imaging of autonomous lymphatic vessel contraction. Using this method, we demonstrated that endothelial nitric oxide synthase (eNOS) in lymphatic endothelial cells is required for robust lymphatic contractions under physiological conditions. By contrast, under inflammatory conditions, inducible NOS (iNOS)-expressing CD11b(+)Gr-1(+) cells attenuate lymphatic contraction. This inhibition of lymphatic contraction was associated with a reduction in the response to antigen in a model of immune induced multiple sclerosis. These results suggest the suppression of lymphatic function by the CD11b(+)Gr-1(+) cells as a potential mechanism of self-protection from autoreactive responses during on-going inflammation. The central role for nitric oxide also suggests that other diseases such as cancer and infection may also mediate lymphatic contraction and thus immune response. Our unique method allows the study of lymphatic function and its molecular regulation during inflammation, lymphedema, and lymphatic metastasis. PMID- 22065739 TI - Anthropogenic fire drives the evolution of seed traits. AB - Fire is a major disturbance affecting ecosystems worldwide. Phylogenetic studies have shown that the evolution of seed persistence (fire resistance) is associated with fire frequency or severity. However, the existence of specific seed traits resulting from natural selection mediated by fire remains a key question in plant evolution. We evaluated the role of fire in the evolution of seed traits from a microevolutionary perspective, using as a study system a native forb from the Chilean matorral, where fire is a novel, anthropogenic disturbance. We show that anthropogenic fires are shaping the evolution of seed traits such as pubescence and shape. Among-population variation in seed pubescence, shape, and pericarp thickness was strongly associated with fire frequency, and within a population, fire selected those plants with more pubescent seeds, thicker pericarps, and less rounded seeds. Seed pubescence and shape were shown to be heritable traits. Our findings provide insights into the understanding of the evolution of seed traits in fire-prone environments and demonstrate that human-made fires can be driving evolutionary changes in plant species from ecosystems where fires do not occur naturally. PMID- 22065740 TI - Role of type 2 deiodinase in response to acute lung injury (ALI) in mice. AB - Thyroid hormone (TH) metabolism, mediated by deiodinase types 1, 2, and 3 (D1, D2, and D3) is profoundly affected by acute illness. We examined the role of TH metabolism during ventilator-induced lung injury (VILI) in mice. Mice exposed to VILI recapitulated the serum TH findings of acute illness, namely a decrease in 3,5,3'-triiodothyronine (T(3)) and thyroid-stimulating hormone and an increase in reverse T(3). Both D2 immunoreactivity and D2 enzymatic activity were increased significantly. D1 and D3 activity did not change. Using D2 knockout (D2KO) mice, we determined whether the increase in D2 was an adaptive response. Although similar changes in serum TH levels were observed in D2KO and WT mice, D2KO mice exhibited greater susceptibility to VILI than WT mice, as evidenced by poorer alveoli integrity and quantified by lung chemokine and cytokine mRNA induction. These data suggest that an increase in lung D2 is protective against VILI. Similar findings of increased inflammatory markers were found in hypothyroid WT mice exposed to VILI compared with euthyroid mice, indicating that the lungs were functionally hypothyroid. Treatment of D2KO mice with T(3) reversed many of the lung chemokine and cytokine profiles seen in response to VILI, demonstrating a role for T(3) in the treatment of lung injury. We conclude that TH metabolism in the lung is linked to the response to inflammatory injury and speculate that D2 exerts its protective effect by making more TH available to the injured lung tissue. PMID- 22065741 TI - Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia. AB - Neural stem/progenitor cell proliferation and differentiation are required to replace damaged neurons and regain brain function after hypoxic-ischemic events. DNA base lesions accumulating during hypoxic-ischemic stress are removed by DNA glycosylases in the base-excision repair pathway to prevent cytotoxicity and mutagenesis. Expression of the DNA glycosylase endonuclease VIII-like 3 (Neil3) is confined to regenerative subregions in the embryonic and perinatal brains. Here we show profound neuropathology in Neil3-knockout mice characterized by a reduced number of microglia and loss of proliferating neuronal progenitors in the striatum after hypoxia-ischemia. In vitro expansion of Neil3-deficient neural stem/progenitor cells revealed an inability to augment neurogenesis and a reduced capacity to repair for oxidative base lesions in single-stranded DNA. We propose that Neil3 exercises a highly specialized function through accurate molecular repair of DNA in rapidly proliferating cells. PMID- 22065742 TI - HSV-1 gene expression from reactivated ganglia is disordered and concurrent with suppression of latency-associated transcript and miRNAs. AB - In cell cultures, HSV-1 replication is initiated by recruitment by virion protein 16 of transcriptional factors and histone-modifying enzymes to immediate early (alpha) gene promoters. HSV establishes latent infections characterized by suppression of viral gene expression except for latency-associated transcripts (LATs) and miRNAs. The latent virus reactivates in stressed neurons. A fundamental question is how reactivation initiates in the absence of virion protein 16. We report the following findings in the ganglion explant model. (i) Anti-nerve growth factor antibody accelerated the reactivation of latent virus. Viral mRNAs were detected as early as 9 h after explantation. (ii) After explantation the amounts of viral mRNAs increased whereas amounts of miRNAs and LATs decreased. The decrease in miRNAs and LATs required ongoing protein synthesis, raising the possibility that LAT and miRNAs were degraded by a viral gene product. (iii) The expression of viral genes in explanted ganglia was disordered rather than sequentially ordered as in infected cells in culture. These findings suggest that in reactivating ganglia gene expression is totally derepressed and challenge the current models in that establishment of or exit from latency could not be dependent on the suppression or activation of single or small clusters of viral genes. Finally, miRNAs and LATs reached peak levels 9-11 d after corneal inoculation, thus approximating the pattern of virus replication in these ganglia. These findings suggest that the patterns of accumulation of LATs and miRNAs reflect many different stages in the infection of neurons. PMID- 22065743 TI - Phytoplasma protein effector SAP11 enhances insect vector reproduction by manipulating plant development and defense hormone biosynthesis. AB - Phytoplasmas are insect-transmitted phytopathogenic bacteria that can alter plant morphology and the longevity and reproduction rates and behavior of their insect vectors. There are various examples of animal and plant parasites that alter the host phenotype to attract insect vectors, but it is unclear how these parasites accomplish this. We hypothesized that phytoplasmas produce effectors that modulate specific targets in their hosts leading to the changes in plant development and insect performance. Previously, we sequenced and mined the genome of Aster Yellows phytoplasma strain Witches' Broom (AY-WB) and identified 56 candidate effectors. Here, we report that the secreted AY-WB protein 11 (SAP11) effector modulates plant defense responses to the advantage of the AY-WB insect vector Macrosteles quadrilineatus. SAP11 binds and destabilizes Arabidopsis CINCINNATA (CIN)-related TEOSINTE BRANCHED1, CYCLOIDEA, PROLIFERATING CELL FACTORS 1 and 2 (TCP) transcription factors, which control plant development and promote the expression of lipoxygenase (LOX) genes involved in jasmonate (JA) synthesis. Both the Arabidopsis SAP11 lines and AY-WB-infected plants produce less JA on wounding. Furthermore, the AY-WB insect vector produces more offspring on AY-WB-infected plants, SAP11 transgenic lines, and plants impaired in CIN-TCP and JA synthesis. Thus, SAP11-mediated destabilization of CIN-TCPs leads to the down-regulation of LOX2 expression and JA synthesis and an increase in M. quadrilineatus progeny. Phytoplasmas are obligate inhabitants of their plant host and insect vectors, in which the latter transmits AY-WB to a diverse range of plant species. This finding demonstrates that pathogen effectors can reach beyond the pathogen-host interface to modulate a third organism in the biological interaction. PMID- 22065744 TI - Lower specific infectivity of protease-resistant prion protein generated in cell free reactions. AB - Prions are unconventional infectious agents that cause transmissible spongiform encephalopathy (TSE) diseases, or prion diseases. The biochemical nature of the prion infectious agent remains unclear. Previously, using a protein misfolding cyclic amplification (PMCA) reaction, infectivity and disease-associated protease resistant prion protein (PrPres) were both generated under cell-free conditions, which supported a nonviral hypothesis for the agent. However, these studies lacked comparative quantitation of both infectivity titers and PrPres, which is important both for biological comparison with in vivo-derived infectivity and for excluding contamination to explain the results. Here during four to eight rounds of PMCA, end-point dilution titrations detected a >320-fold increase in infectivity versus that in controls. These results provide strong support for the hypothesis that the agent of prion infectivity is not a virus. PMCA-generated samples caused the same clinical disease and neuropathology with the same rapid incubation period as the input brain-derived scrapie samples, providing no evidence for generation of a new strain in PMCA. However, the ratio of the infectivity titer to the amount of PrPres (specific infectivity) was much lower in PMCA versus brain-derived samples, suggesting the possibility that a substantial portion of PrPres generated in PMCA might be noninfectious. PMID- 22065745 TI - Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth. AB - Understanding neurite growth regulation remains a seminal problem in neurobiology. During development and regeneration, neurite growth is modulated by neurotrophin-activated signaling endosomes that transmit regulatory signals between soma and growth cones. After injury, delivering neurotrophic therapeutics to injured neurons is limited by our understanding of how signaling endosome localization in the growth cone affects neurite growth. Nanobiotechnology is providing new tools to answer previously inaccessible questions. Here, we show superparamagnetic nanoparticles (MNPs) functionalized with TrkB agonist antibodies are endocytosed into signaling endosomes by primary neurons that activate TrkB-dependent signaling, gene expression and promote neurite growth. These MNP signaling endosomes are trafficked into nascent and existing neurites and transported between somas and growth cones in vitro and in vivo. Manipulating MNP-signaling endosomes by a focal magnetic field alters growth cone motility and halts neurite growth in both peripheral and central nervous system neurons, demonstrating signaling endosome localization in the growth cone regulates motility and neurite growth. These data suggest functionalized MNPs may be used as a platform to study subcellular organelle localization and to deliver nanotherapeutics to treat injury or disease in the central nervous system. PMID- 22065747 TI - Conserved metabolic energy production pathways govern Eiger/TNF-induced nonapoptotic cell death. AB - Caspase-independent cell death is known to be important in physiological and pathological conditions, but its molecular regulation is not well-understood. Eiger is the sole fly ortholog of TNF. The ectopic expression of Eiger in the developing eye primordium caused JNK-dependent but caspase-independent cell death. To understand the molecular basis of this Eiger-induced nonapoptotic cell death, we performed a large-scale genetic screen in Drosophila for suppressors of the Eiger-induced cell death phenotype. We found that molecules that regulate metabolic energy production are central to this form of cell death: it was dramatically suppressed by decreased levels of molecules that regulate cytosolic glycolysis, mitochondrial beta-oxidation of fatty acids, the tricarboxylic acid cycle, and the electron transport chain. Importantly, reducing the expression of energy production-related genes did not affect the cell death triggered by proapoptotic genes, such as reaper, hid, or debcl, indicating that the energy production-related genes have a specific role in Eiger-induced nonapoptotic cell death. We also found that energy production-related genes regulate the Eiger induced cell death downstream of JNK. In addition, Eiger induced the production of reactive oxygen species in a manner dependent on energy production-related genes. Furthermore, we showed that this cell death machinery is involved in Eiger's physiological function, because decreasing the energy production-related genes suppressed Eiger-dependent tumor suppression, an intrinsic mechanism for removing tumorigenic mutant clones from epithelia by inducing cell death. This result suggests a link between sensitivity to cell death and metabolic activity in cancer. PMID- 22065748 TI - Metabolic cycling without cell division cycling in respiring yeast. AB - Despite rapid progress in characterizing the yeast metabolic cycle, its connection to the cell division cycle (CDC) has remained unclear. We discovered that a prototrophic batch culture of budding yeast, growing in a phosphate limited ethanol medium, synchronizes spontaneously and goes through multiple metabolic cycles, whereas the fraction of cells in the G1/G0 phase of the CDC increases monotonically from 90 to 99%. This demonstrates that metabolic cycling does not require cell division cycling and that metabolic synchrony does not require carbon-source limitation. More than 3,000 genes, including most genes annotated to the CDC, were expressed periodically in our batch culture, albeit a mere 10% of the cells divided asynchronously; only a smaller subset of CDC genes correlated with cell division. These results suggest that the yeast metabolic cycle reflects a growth cycle during G1/G0 and explains our previous puzzling observation that genes annotated to the CDC increase in expression at slow growth. PMID- 22065749 TI - Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers. AB - Activation of the PI3K and epidermal growth factor receptor (EGFR) pathway is able to drive oncogenesis in multiple human cancers, including head and neck squamous cell carcinoma. Targeted agents such as cetuximab and erlotinib are currently used in patients with head and neck squamous cell carcinoma, but, in this disease, the genomic alterations that cause pathway activation and determine response to pharmacologic inhibition remain ill-defined. Here, we present a detailed dissection of the EGFR/PI3K pathway, composed of sequencing of the core pathway components, and high-resolution genomic copy number assessment. Mutations were found in PIK3CA (6%), but no point mutations were observed in other pathway genes such as PTEN and EGFR. In contrast, we observed frequent copy number alterations of genes in the pathway, including PIK3CA, EGFR, protein tyrosine phosphatase receptor S (PTPRS), and RICTOR. In total, activating genetic pathway alterations were identified in 74% of head and neck tumors. Importantly, intragenic microdeletions of the EGFR phosphatase PTPRS were frequent (26%), identifying this gene as a target of 19p13 loss. PTPRS loss promoted EGFR/PI3K pathway activation, modulated resistance to EGFR inhibition, and strongly determined survival in lung cancer patients with activating EGFR mutations. These findings have important implications for our understanding of head and neck cancer tumorigenesis and for the use of targeted agents for this malignancy. PMID- 22065750 TI - Sulfanyl stabilization of copper-bonded phenoxyls in model complexes and galactose oxidase. AB - Integrating sulfanyl substituents into copper-bonded phenoxyls significantly alters their optical and redox properties and provides insight into the influence of cysteine modification of the tyrosine cofactor in the enzyme galactose oxidase. The model complexes [1(SR2)](+) are class II mixed-valent Cu(II) phenoxyl-phenolate species that exhibit intervalence charge transfer bands and intense visible sulfur-aryl pi -> pi* transitions in the energy range, which provides a greater spectroscopic fidelity to oxidized galactose oxidase than non sulfur-bearing analogs. The potentials for phenolate-based oxidations of the sulfanyl-substituted 1(SR2) are lower than the alkyl-substituted analogs by up to ca. 150 mV and decrease following the steric trend: -S(t)Bu > -S(i) Pr > -SMe. Density functional theory calculations suggest that reducing the steric demands of the sulfanyl substituent accommodates an in-plane conformation of the alkylsulfanyl group with the aromatic ring, which stabilizes the phenoxyl hole by ca. 8 kcal mol(-1) (1 kcal = 4.18 kJ; 350 mV) through delocalization onto the sulfur atom. Sulfur K-edge X-ray absorption spectroscopy clearly indicates a contribution of ca. 8-13% to the hole from the sulfur atoms in [1(SR2)](+). The electrochemical results for the model complexes corroborate the ca. 350 mV (density functional theory) contribution of hole delocalization on to the cysteine-tyrosine cross-link to the stability of the phenoxyl radical in the enzyme, while highlighting the importance of the in-plane conformation observed in all crystal structures of the enzyme. PMID- 22065751 TI - Influence of coastal vegetation on the 2004 tsunami wave impact in west Aceh. AB - In a tsunami event human casualties and infrastructure damage are determined predominantly by seaquake intensity and offshore properties. On land, wave energy is attenuated by gravitation (elevation) and friction (land cover). Tree belts have been promoted as "bioshields" against wave impact. However, given the lack of quantitative evidence of their performance in such extreme events, tree belts have been criticized for creating a false sense of security. This study used 180 transects perpendicular to over 100 km on the west coast of Aceh, Indonesia to analyze the influence of coastal vegetation, particularly cultivated trees, on the impact of the 2004 tsunami. Satellite imagery; land cover maps; land use characteristics; stem diameter, height, and planting density; and a literature review were used to develop a land cover roughness coefficient accounting for the resistance offered by different land uses to the wave advance. Applying a spatial generalized linear mixed model, we found that while distance to coast was the dominant determinant of impact (casualties and infrastructure damage), the existing coastal vegetation in front of settlements also significantly reduced casualties by an average of 5%. In contrast, dense vegetation behind villages endangered human lives and increased structural damage. Debris carried by the backwash may have contributed to these dissimilar effects of land cover. For sustainable and effective coastal risk management, location of settlements is essential, while the protective potential of coastal vegetation, as determined by its spatial arrangement, should be regarded as an important livelihood provider rather than just as a bioshield. PMID- 22065752 TI - Time-resolved structural dynamics of thin metal films heated with femtosecond optical pulses. AB - We utilize 100 fs optical pulses to induce ultrafast disorder of 35- to 150-nm thick single Au(111) crystals and observe the subsequent structural evolution using 0.6-ps, 8.04-keV X-ray pulses. Monitoring the picosecond time-dependent modulation of the X-ray diffraction intensity, width, and shift, we have measured directly electron/phonon coupling, phonon/lattice interaction, and a histogram of the lattice disorder evolution, such as lattice breath due to a pressure wave propagating at sonic velocity, lattice melting, and recrystallization, including mosaic formation. Results of theoretical simulations agree and support the experimental data of the lattice/liquid phase transition process. These time resolved X-ray diffraction data provide a detailed description of all the significant processes induced by ultrafast laser pulses impinging on thin metallic single crystals. PMID- 22065753 TI - Heat shock protein 70 kDa chaperone/DnaJ cochaperone complex employs an unusual dynamic interface. AB - The heat shock protein 70 kDa (Hsp70)/DnaJ/nucleotide exchange factor system assists in intracellular protein (re)folding. Using solution NMR, we obtained a three-dimensional structure for a 75-kDa Hsp70-DnaJ complex in the ADP state, loaded with substrate peptide. We establish that the J domain (residues 1-70) binds with its positively charged helix II to a negatively charged loop in the Hsp70 nucleotide-binding domain. The complex shows an unusual "tethered" binding mode which is stoichiometric and saturable, but which has a dynamic interface. The complex represents part of a triple complex of Hsp70 and DnaJ both bound to substrate protein. Mutagenesis data indicate that the interface is also of relevance for the interaction of Hsp70 and DnaJ in the ATP state. The solution complex is completely different from a crystal structure of a disulfide-linked complex of homologous proteins [Jiang, et al. (2007) Mol Cell 28:422-433]. PMID- 22065754 TI - Copy number variation detection in whole-genome sequencing data using the Bayesian information criterion. AB - DNA copy number variations (CNVs) play an important role in the pathogenesis and progression of cancer and confer susceptibility to a variety of human disorders. Array comparative genomic hybridization has been used widely to identify CNVs genome wide, but the next-generation sequencing technology provides an opportunity to characterize CNVs genome wide with unprecedented resolution. In this study, we developed an algorithm to detect CNVs from whole-genome sequencing data and applied it to a newly sequenced glioblastoma genome with a matched control. This read-depth algorithm, called BIC-seq, can accurately and efficiently identify CNVs via minimizing the Bayesian information criterion. Using BIC-seq, we identified hundreds of CNVs as small as 40 bp in the cancer genome sequenced at 10* coverage, whereas we could only detect large CNVs (> 15 kb) in the array comparative genomic hybridization profiles for the same genome. Eighty percent (14/16) of the small variants tested (110 bp to 14 kb) were experimentally validated by quantitative PCR, demonstrating high sensitivity and true positive rate of the algorithm. We also extended the algorithm to detect recurrent CNVs in multiple samples as well as deriving error bars for breakpoints using a Gibbs sampling approach. We propose this statistical approach as a principled yet practical and efficient method to estimate CNVs in whole-genome sequencing data. PMID- 22065755 TI - alpha-Synuclein fate is determined by USP9X-regulated monoubiquitination. AB - alpha-Synuclein is central to the pathogenesis of Parkinson disease (PD). Mutations as well as accumulation of alpha-synuclein promote the death of dopaminergic neurons and the formation of Lewy bodies. alpha-Synuclein is monoubiquitinated by SIAH, but the regulation and roles of monoubiquitination in alpha-synuclein biology are poorly understood. We now report that the deubiquitinase USP9X interacts in vivo with and deubiquitinates alpha-synuclein. USP9X levels are significantly lower in cytosolic fractions of PD substantia nigra and Diffuse Lewy Body disease (DLBD) cortices compared to controls. This was associated to lower deubiquitinase activity toward monoubiquitinated alpha synuclein in DLBD cortical extracts. A fraction of USP9X seems to be aggregated in PD and DLBD, as USP9X immunoreactivity is detected in Lewy bodies. Knockdown of USP9X expression promotes accumulation of monoubiquitinated alpha-synuclein species and enhances the formation of toxic alpha-synuclein inclusions upon proteolytic inhibition. On the other hand, by manipulating USP9X expression levels in the absence of proteolytic impairment, we demonstrate that monoubiquitination controls the partition of alpha-synuclein between different protein degradation systems. Deubiquitinated alpha-synuclein is mostly degraded by autophagy, while monoubiquitinated alpha-synuclein is preferentially degraded by the proteasome. Moreover, monoubiquitination promotes the degradation of alpha synuclein, whereas deubiquitination leads to its accumulation, suggesting that the degradation of deubiquitinated alpha-synuclein by the autophagy pathway is less efficient than the proteasomal one. Lower levels of cytosolic USP9X and deubiquitinase activity in alpha-synucleinopathies may contribute to the accumulation and aggregation of monoubiquitinated alpha-synuclein in Lewy bodies. Our data indicate that monoubiquitination is a key determinant of alpha-synuclein fate. PMID- 22065756 TI - Terminal protein-primed amplification of heterologous DNA with a minimal replication system based on phage Phi29. AB - The DNA amplification performed by terminal protein-primed replication systems has not yet been developed for its general use to produce high amounts of DNA linked to terminal protein (TP). Here we present a method to amplify in vitro heterologous DNAs using the Phi29 DNA replication machinery and producing DNA with TP covalently attached to the 5' end. The amplification requires four Phi29 proteins, DNA polymerase, TP, single-stranded DNA binding protein and double stranded DNA binding protein (p6). The DNA to be amplified is inserted between two sequences that are the Phi29 DNA replication origins, consisting of 191 and 194 bp from the left and right ends of the phage genome, respectively. The replication origins do not need to have TP covalently attached beforehand to be functional in amplification and they can be joined to the DNA to be amplified by cloning or ligation. The facts that two functional origins were required at the ends of a linear template DNA and that the kinetics of DNA synthesis was very similar to that obtained using the TP-containing Phi29 genome as template support the proposal that genuine amplification is taking place. Amplification factors of 30-fold have been obtained. Possible applications of DNAs produced by this method are discussed. PMID- 22065757 TI - Femtosecond dynamics coupled to chemical barrier crossing in a Born-Oppenheimer enzyme. AB - Contributions of fast (femtosecond) dynamic motion to barrier crossing at enzyme catalytic sites is in dispute. Human purine nucleoside phosphorylase (PNP) forms a ribocation-like transition state in the phosphorolysis of purine nucleosides and fast protein motions have been proposed to participate in barrier crossing. In the present study, (13)C-, (15)N-, (2)H-labeled human PNP (heavy PNP) was expressed, purified to homogeneity, and shown to exhibit a 9.9% increase in molecular mass relative to its unlabeled counterpart (light PNP). Kinetic isotope effects and steady-state kinetic parameters were indistinguishable for both enzymes, indicating that transition-state structure, equilibrium binding steps, and the rate of product release were not affected by increased protein mass. Single-turnover rate constants were slowed for heavy PNP, demonstrating reduced probability of chemical barrier crossing from enzyme-bound substrates to enzyme bound products. In a second, independent method to probe barrier crossing, heavy PNP exhibited decreased forward commitment factors, also revealing mass-dependent decreased probability for barrier crossing. Increased atomic mass in human PNP alters bond vibrational modes on the femtosecond time scale and reduces on-enzyme chemical barrier crossing. This study demonstrates coupling of enzymatic bond vibrations on the femtosecond time scale to barrier crossing. PMID- 22065758 TI - Insights regarding guanine nucleotide exchange from the structure of a DENN domain protein complexed with its Rab GTPase substrate. AB - Rab GTPases are key regulators of membrane traffic pathways within eukaryotic cells. They are specifically activated by guanine nucleotide exchange factors (GEFs), which convert them from their "inactive" GDP-bound form to the "active" GTP-bound form. In higher eukaryotes, proteins containing DENN-domains comprise a major GEF family. Here we describe at 2.1-A resolution the first structure of a DENN-domain protein, DENND1B-S, complexed with its substrate Rab35, providing novel insights as to how DENN-domain GEFs interact with and activate Rabs. DENND1B-S is bi-lobed, and interactions with Rab35 are through conserved surfaces in both lobes. Rab35 binds via switch regions I and II, around the nucleotide binding pocket. Positional shifts in Rab residues required for nucleotide binding may lower its affinity for bound GDP, and a conformational change in switch I, which makes the nucleotide-binding pocket more solvent accessible, likely also facilitates exchange. PMID- 22065759 TI - Inferring the rules of interaction of shoaling fish. AB - Collective motion, where large numbers of individuals move synchronously together, is achieved when individuals adopt interaction rules that determine how they respond to their neighbors' movements and positions. These rules determine how group-living animals move, make decisions, and transmit information between individuals. Nonetheless, few studies have explicitly determined these interaction rules in moving groups, and very little is known about the interaction rules of fish. Here, we identify three key rules for the social interactions of mosquitofish (Gambusia holbrooki): (i) Attraction forces are important in maintaining group cohesion, while we find only weak evidence that fish align with their neighbor's orientation; (ii) repulsion is mediated principally by changes in speed; (iii) although the positions and directions of all shoal members are highly correlated, individuals only respond to their single nearest neighbor. The last two of these rules are different from the classical models of collective animal motion, raising new questions about how fish and other animals self-organize on the move. PMID- 22065760 TI - Nanostructure of cellulose microfibrils in spruce wood. AB - The structure of cellulose microfibrils in wood is not known in detail, despite the abundance of cellulose in woody biomass and its importance for biology, energy, and engineering. The structure of the microfibrils of spruce wood cellulose was investigated using a range of spectroscopic methods coupled to small-angle neutron and wide-angle X-ray scattering. The scattering data were consistent with 24-chain microfibrils and favored a "rectangular" model with both hydrophobic and hydrophilic surfaces exposed. Disorder in chain packing and hydrogen bonding was shown to increase outwards from the microfibril center. The extent of disorder blurred the distinction between the I alpha and I beta allomorphs. Chains at the surface were distinct in conformation, with high levels of conformational disorder at C-6, less intramolecular hydrogen bonding and more outward-directed hydrogen bonding. Axial disorder could be explained in terms of twisting of the microfibrils, with implications for their biosynthesis. PMID- 22065761 TI - Evolution of D-lactate dehydrogenase activity from glycerol dehydrogenase and its utility for D-lactate production from lignocellulose. AB - Lactic acid, an attractive, renewable chemical for production of biobased plastics (polylactic acid, PLA), is currently commercially produced from food based sources of sugar. Pure optical isomers of lactate needed for PLA are typically produced by microbial fermentation of sugars at temperatures below 40 degrees C. Bacillus coagulans produces L(+)-lactate as a primary fermentation product and grows optimally at 50 degrees C and pH 5, conditions that are optimal for activity of commercial fungal cellulases. This strain was engineered to produce D(-)-lactate by deleting the native ldh (L-lactate dehydrogenase) and alsS (acetolactate synthase) genes to impede anaerobic growth, followed by growth based selection to isolate suppressor mutants that restored growth. One of these, strain QZ19, produced about 90 g L(-1) of optically pure D(-)-lactic acid from glucose in < 48 h. The new source of D-lactate dehydrogenase (D-LDH) activity was identified as a mutated form of glycerol dehydrogenase (GlyDH; D121N and F245S) that was produced at high levels as a result of a third mutation (insertion sequence). Although the native GlyDH had no detectable activity with pyruvate, the mutated GlyDH had a D-LDH specific activity of 0.8 MUmoles min(-1) (mg protein)(-1). By using QZ19 for simultaneous saccharification and fermentation of cellulose to D-lactate (50 degrees C and pH 5.0), the cellulase usage could be reduced to 1/3 that required for equivalent fermentations by mesophilic lactic acid bacteria. Together, the native B. coagulans and the QZ19 derivative can be used to produce either L(+) or D(-) optical isomers of lactic acid (respectively) at high titers and yields from nonfood carbohydrates. PMID- 22065762 TI - Niemann-Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding. AB - Niemann-Pick type C1 (NPC1) protein is needed for cellular utilization of low density lipoprotein-derived cholesterol that has been delivered to lysosomes. The protein has 13 transmembrane domains, three large lumenal domains, and a cytoplasmic tail. NPC1's lumenally oriented, N-terminal domain binds cholesterol and has been proposed to receive cholesterol from NPC2 protein as part of the process by which cholesterol is exported from lysosomes into the cytosol. Using surface plasmon resonance and affinity chromatography, we show here that the second lumenal domain of NPC1 binds directly to NPC2 protein. For these experiments, a soluble NPC1 lumenal domain 2 was engineered by replacing adjacent transmembrane domains with antiparallel coiled-coil sequences. Interaction of NPC2 with NPC1 lumenal domain 2 is only detected at acidic pH, conditions that are optimal for cholesterol binding to NPC2 and transfer to NPC1; the pH is also appropriate for the acidic environment where binding would take place. Binding to NPC1 domain 2 requires the presence of cholesterol on NPC2 protein, a finding that supports directional transfer of cholesterol from NPC2 onto NPC1's N terminal domain. Finally, human disease-causing mutations in NPC1 domain 2 decrease NPC2 binding, suggesting that NPC2 binding is necessary for NPC1 function in humans. These data support a model in which NPC1 domain 2 holds NPC2 in position to facilitate directional cholesterol transfer from NPC2 onto NPC1 protein for export from lysosomes. PMID- 22065763 TI - Algorithm discovery by protein folding game players. AB - Foldit is a multiplayer online game in which players collaborate and compete to create accurate protein structure models. For specific hard problems, Foldit player solutions can in some cases outperform state-of-the-art computational methods. However, very little is known about how collaborative gameplay produces these results and whether Foldit player strategies can be formalized and structured so that they can be used by computers. To determine whether high performing player strategies could be collectively codified, we augmented the Foldit gameplay mechanics with tools for players to encode their folding strategies as "recipes" and to share their recipes with other players, who are able to further modify and redistribute them. Here we describe the rapid social evolution of player-developed folding algorithms that took place in the year following the introduction of these tools. Players developed over 5,400 different recipes, both by creating new algorithms and by modifying and recombining successful recipes developed by other players. The most successful recipes rapidly spread through the Foldit player population, and two of the recipes became particularly dominant. Examination of the algorithms encoded in these two recipes revealed a striking similarity to an unpublished algorithm developed by scientists over the same period. Benchmark calculations show that the new algorithm independently discovered by scientists and by Foldit players outperforms previously published methods. Thus, online scientific game frameworks have the potential not only to solve hard scientific problems, but also to discover and formalize effective new strategies and algorithms. PMID- 22065764 TI - Complementing apolipoprotein secretion by cultured retinal pigment epithelium. PMID- 22065765 TI - Separation of stem cell maintenance and transposon silencing functions of Piwi protein. AB - Piwi-interacting RNAs (piRNAs) and Piwi proteins have the evolutionarily conserved function of silencing of repetitive genetic elements in germ lines. The founder of the Piwi subfamily, Drosophila nuclear Piwi protein, was also shown to be required for the maintenance of germ-line stem cells (GSCs). Hence, null mutant piwi females exhibit two types of abnormalities, overexpression of transposons and severely underdeveloped ovaries. It remained unknown whether the failure of GSC maintenance is related to transposon derepression or if GSC self renewal and piRNA silencing are two distinct functions of the Piwi protein. We have revealed a mutation, piwi(Nt), removing the nuclear localization signal of the Piwi protein. piwi(Nt) females retain the ability of GSC self-renewal and a near-normal number of egg chambers in the ovarioles but display a drastic transposable element derepression and nuclear accumulation of their transcripts in the germ line. piwi(Nt) mutants are sterile most likely because of the disturbance of piRNA-mediated transposon silencing. Analysis of chromatin modifications in the piwi(Nt) ovaries indicated that Piwi causes chromatin silencing only of certain types of transposons, whereas others are repressed in the nuclei without their chromatin modification. Thus, Piwi nuclear localization that is required for its silencing function is not essential for the maintenance of GSCs. We suggest that the Piwi function in GSC self-renewal is independent of transposon repression and is normally realized in the cytoplasm of GSC niche cells. PMID- 22065766 TI - The musculoskeletal system of humans is not tuned to maximize the economy of locomotion. AB - Humans are known to have energetically optimal walking and running speeds at which the cost to travel a given distance is minimized. We hypothesized that "optimal" walking and running speeds would also exist at the level of individual locomotor muscles. Additionally, because humans are 60-70% more economical when they walk than when they run, we predicted that the different muscles would exhibit a greater degree of tuning to the energetically optimal speed during walking than during running. To test these hypotheses, we used electromyography to measure the activity of 13 muscles of the back and legs over a range of walking and running speeds in human subjects and calculated the cumulative activity required from each muscle to traverse a kilometer. We found that activity of each of these muscles was minimized at specific walking and running speeds but the different muscles were not tuned to a particular speed in either gait. Although humans are clearly highly specialized for terrestrial locomotion compared with other great apes, the results of this study indicate that our locomotor muscles are not tuned to specific walking or running speeds and, therefore, do not maximize the economy of locomotion. This pattern may have evolved in response to selection to broaden the range of sustainable running speeds, to improve performance in motor behaviors not related to endurance locomotion, or in response to selection for both. PMID- 22065767 TI - Vbeta2 natural killer T cell antigen receptor-mediated recognition of CD1d glycolipid antigen. AB - Natural killer T cell antigen receptors (NKT TCRs) recognize lipid-based antigens (Ags) presented by CD1d. Although the TCR alpha-chain is invariant, NKT TCR Vbeta exhibits greater diversity, with one (Vbeta11) and three (Vbeta8, Vbeta7, and Vbeta2) Vbeta chains in humans and mice, respectively. With the exception of the Vbeta2 NKT TCR, NKT TCRs possess canonical tyrosine residues within complementarity determining region (CDR) 2beta that are critical for CD1d binding. Thus, how Vbeta2 NKT TCR docks with CD1d-Ag was unclear. Despite the absence of the CDR2beta-encoded tyrosine residues, we show that the Vbeta2 NKT TCR engaged CD1d-Ag in a similar manner and with a comparable affinity and energetic footprint to the manner observed for the Vbeta8.2 and Vbeta7 NKT TCRs. Accordingly, the germline-encoded regions of the TCR beta-chain do not exclusively dictate the innate NKT TCR-CD1d-Ag docking mode. Nevertheless, clear fine specificity differences for the CD1d-Ag existed between the Vbeta2 NKT TCR and the Vbeta8.2 and Vbeta7 NKT TCRs, with the Vbeta2 NKT TCR exhibiting greater sensitivity to modifications to the glycolipid Ag. Furthermore, within the Vbeta2 NKT TCR-CD1d-alphaGalCer complex, the CDR2beta loop mediated fewer contacts with CD1d, whereas the CDR1beta and CDR3beta loops contacted CD1d to a much greater extent compared with most Vbeta11, Vbeta8.2, and Vbeta7 NKT TCRs. Accordingly, there is a greater interplay between the germline- and nongermline-encoded loops within the TCR beta-chain of the Vbeta2 NKT TCR that enables CD1d-Ag ligation. PMID- 22065768 TI - Surface-engineered substrates for improved human pluripotent stem cell culture under fully defined conditions. AB - The current gold standard for the culture of human pluripotent stem cells requires the use of a feeder layer of cells. Here, we develop a spatially defined culture system based on UV/ozone radiation modification of typical cell culture plastics to define a favorable surface environment for human pluripotent stem cell culture. Chemical and geometrical optimization of the surfaces enables control of early cell aggregation from fully dissociated cells, as predicted from a numerical model of cell migration, and results in significant increases in cell growth of undifferentiated cells. These chemically defined xeno-free substrates generate more than three times the number of cells than feeder-containing substrates per surface area. Further, reprogramming and typical gene-targeting protocols can be readily performed on these engineered surfaces. These substrates provide an attractive cell culture platform for the production of clinically relevant factor-free reprogrammed cells from patient tissue samples and facilitate the definition of standardized scale-up friendly methods for disease modeling and cell therapeutic applications. PMID- 22065769 TI - Fcgamma receptor IIB (FcgammaRIIB) maintains humoral tolerance in the human immune system in vivo. AB - Maintenance of immunological tolerance is crucial to prevent development of autoimmune disease. The production of autoantibodies is a hallmark of many autoimmune diseases and studies in mouse model systems suggest that inhibitory signaling molecules may be important checkpoints of humoral tolerance. By generating humanized mice with normal and functionally impaired Fcgamma receptor IIB (FcgammaRIIB) variants, we show that the inhibitory Fcgamma-receptor is a checkpoint of humoral tolerance in the human immune system in vivo. Impaired human FcgammaRIIB function resulted in the generation of higher levels of serum immunoglobulins, the production of different autoantibody specificities, and a higher proportion of human plasmablasts and plasma cells in vivo. Our results suggest that the inhibitory FcgammaRIIB may be an important checkpoint of humoral tolerance in the human immune system. PMID- 22065770 TI - Keeping proteasomes under control--a role for phosphorylation in the nucleus. PMID- 22065771 TI - Energetic consequences of thermal and nonthermal food processing. AB - Processing food extensively by thermal and nonthermal techniques is a unique and universal human practice. Food processing increases palatability and edibility and has been argued to increase energy gain. Although energy gain is a well-known effect from cooking starch-rich foods, the idea that cooking meat increases energy gain has never been tested. Moreover, the relative energetic advantages of cooking and nonthermal processing have not been assessed, whether for meat or starch-rich foods. Here, we describe a system for characterizing the energetic effects of cooking and nonthermal food processing. Using mice as a model, we show that cooking substantially increases the energy gained from meat, leading to elevations in body mass that are not attributable to differences in food intake or activity levels. The positive energetic effects of cooking were found to be superior to the effects of pounding in both meat and starch-rich tubers, a conclusion further supported by food preferences in fasted animals. Our results indicate significant contributions from cooking to both modern and ancestral human energy budgets. They also illuminate a weakness in current food labeling practices, which systematically overestimate the caloric potential of poorly processed foods. PMID- 22065772 TI - Multiple emergences of genetically diverse amphibian-infecting chytrids include a globalized hypervirulent recombinant lineage. AB - Batrachochytrium dendrobatidis (Bd) is a globally ubiquitous fungal infection that has emerged to become a primary driver of amphibian biodiversity loss. Despite widespread effort to understand the emergence of this panzootic, the origins of the infection, its patterns of global spread, and principle mode of evolution remain largely unknown. Using comparative population genomics, we discovered three deeply diverged lineages of Bd associated with amphibians. Two of these lineages were found in multiple continents and are associated with known introductions by the amphibian trade. We found that isolates belonging to one clade, the global panzootic lineage (BdGPL) have emerged across at least five continents during the 20th century and are associated with the onset of epizootics in North America, Central America, the Caribbean, Australia, and Europe. The two newly identified divergent lineages, Cape lineage (BdCAPE) and Swiss lineage (BdCH), were found to differ in morphological traits when compared against one another and BdGPL, and we show that BdGPL is hypervirulent. BdGPL uniquely bears the hallmarks of genomic recombination, manifested as extensive intergenomic phylogenetic conflict and patchily distributed heterozygosity. We postulate that contact between previously genetically isolated allopatric populations of Bd may have allowed recombination to occur, resulting in the generation, spread, and invasion of the hypervirulent BdGPL leading to contemporary disease-driven losses in amphibian biodiversity. PMID- 22065773 TI - RNAi-mediated knockdown of Xist can rescue the impaired postimplantation development of cloned mouse embryos. AB - Cloning mammals by somatic cell nuclear transfer (SCNT) is highly inefficient. Most SCNT-generated embryos die after implantation because of unidentified, complex epigenetic errors in the process of postimplantation embryonic development. Here we identify the most upstream level of dysfunction leading to impaired development of clones by using RNAi against Xist, a gene responsible for X chromosome inactivation (XCI). A prior injection of Xist-specific siRNA into reconstructed oocytes efficiently corrected SCNT-specific aberrant Xist expression at the morula stage, but failed to do so thereafter at the blastocyst stage. However, we found that shortly after implantation, this aberrant XCI status in cloned embryos had been corrected autonomously in both embryonic and extraembryonic tissues, probably through a newly established XCI control for postimplantation embryos. Embryo transfer experiments revealed that siRNA-treated embryos showed 10 times higher survival than controls as early as embryonic day 5.5 and this high survival persisted until term, resulting in a remarkable improvement in cloning efficiency (12% vs. 1% in controls). Importantly, unlike control clones, these Xist-siRNA clones at birth showed only a limited dysregulation of their gene expression, indicating that correction of Xist expression in preimplantation embryos had a long-term effect on their postnatal normality. Thus, contrary to the general assumption, our results suggest that the fate of cloned embryos is determined almost exclusively before implantation by their XCI status. Furthermore, our strategy provides a promising breakthrough for mammalian SCNT cloning, because RNAi treatment of oocytes is readily applicable to most mammal species. PMID- 22065774 TI - RNAi screening reveals requirement for host cell secretory pathway in infection by diverse families of negative-strand RNA viruses. AB - Negative-strand (NS) RNA viruses comprise many pathogens that cause serious diseases in humans and animals. Despite their clinical importance, little is known about the host factors required for their infection. Using vesicular stomatitis virus (VSV), a prototypic NS RNA virus in the family Rhabdoviridae, we conducted a human genome-wide siRNA screen and identified 72 host genes required for viral infection. Many of these identified genes were also required for infection by two other NS RNA viruses, the lymphocytic choriomeningitis virus of the Arenaviridae family and human parainfluenza virus type 3 of the Paramyxoviridae family. Genes affecting different stages of VSV infection, such as entry/uncoating, gene expression, and assembly/release, were identified. Depletion of the proteins of the coatomer complex I or its upstream effectors ARF1 or GBF1 led to detection of reduced levels of VSV RNA. Coatomer complex I was also required for infection of lymphocytic choriomeningitis virus and human parainfluenza virus type 3. These results highlight the evolutionarily conserved requirements for gene expression of diverse families of NS RNA viruses and demonstrate the involvement of host cell secretory pathway in the process. PMID- 22065776 TI - CD95 triggers Orai1-mediated localized Ca2+ entry, regulates recruitment of protein kinase C (PKC) beta2, and prevents death-inducing signaling complex formation. AB - The death receptor CD95 plays a pivotal role in immune surveillance and immune tolerance. Binding of CD95L to CD95 leads to recruitment of the adaptor protein Fas-associated death domain protein (FADD), which in turn aggregates caspase-8 and caspase-10. Efficient formation of the CD95/FADD/caspase complex, known as the death-inducing signaling complex (DISC), culminates in the induction of apoptosis. We show that cells exposed to CD95L undergo a reorganization of the plasma membrane in which the Ca(2+) release-activated Ca(2+) channel Orai1 and the endoplasmic reticulum-resident activator stromal interaction molecule 1 colocalize with CD95 into a micrometer-sized cluster in which the channel elicits a polarized entry of calcium. Orai1 knockdown and expression of a dominant negative construct (Orai1E106A) reveal that on CD95 engagement, the Orai1-driven localized Ca(2+) influx is fundamental to recruiting the Ca(2+)-dependent protein kinase C (PKC) beta2 to the DISC. PKCbeta2 in turn transiently holds the complex in an inactive status, preventing caspase activation and transmission of the apoptotic signal. This study identifies a biological role of Ca(2+) and the Orai1 channel that drives a transient negative feedback loop, introducing a lag phase in the early steps of the CD95 signal. We suggest that these localized events provide a time of decision to prevent accidental cell death. PMID- 22065775 TI - Wip1 promotes RUNX2-dependent apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents. AB - The inactivation of the p53 tumor suppressor pathway in many cancers often increases their resistance to anticancer therapy. Here we show that a previously proposed strategy directed to Wip1 inhibition could be ineffective in tumors lacking p53. On the contrary, Wip1 overexpression sensitized these tumors to chemotherapeutic agents. This effect was mediated through interaction between Wip1 and RUNX2 that resulted, in response to anticancer treatment, in RUNX2 dependent transcriptional induction of the proapoptotic Bax protein. The potentiating effects of Wip1 overexpression on chemotherapeutic agents were directed only to tumor cells lacking p53. The overexpression of Wip1 in normal tissues provided protection from cisplatin-induced apoptosis through decreased strength of upstream signaling to p53. Thus, Wip1 phosphatase promotes apoptosis in p53-negative tumors and protects normal tissues during treatment with anticancer agents. PMID- 22065777 TI - Age dynamics in scientific creativity. AB - Data on Nobel Laureates show that the age-creativity relationship varies substantially more over time than across fields. The age dynamics within fields closely mirror field-specific shifts in (i) training patterns and (ii) the prevalence of theoretical contributions. These dynamics are especially pronounced in physics and coincide with the emergence of quantum mechanics. Taken together, these findings show fundamental shifts in the life cycle of research productivity, inform theories of the age-creativity relationship, and provide observable predictors for the age at which great achievements are made. PMID- 22065778 TI - Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis. AB - Correlations in spontaneous brain activity provide powerful access to large-scale organizational principles of the CNS. However, making inferences about cognitive processes requires a detailed understanding of the link between these couplings and the structural integrity of the CNS. We studied the impact of multiple sclerosis, which leads to the severe disintegration of the central white matter, on functional connectivity patterns in spontaneous cortical activity. Using a data driven approach based on the strength of a salient pattern of cognitive pathology, we identified distinct networks that exhibit increases in functional connectivity despite the presence of strong and diffuse reductions of the central white-matter integrity. The default mode network emerged as a core target of these connectivity modulations, showing enhanced functional coupling in bilateral inferior parietal cortex, posterior cingulate, and medial prefrontal cortex. These findings imply a complex and diverging relation of anatomical and functional connectivity in early multiple sclerosis and, thus, add an important observation for understanding how cognitive abilities and CNS integrity may be reflected in the intrinsic covariance of functional signals. PMID- 22065779 TI - Flux through hepatic pyruvate carboxylase and phosphoenolpyruvate carboxykinase detected by hyperpolarized 13C magnetic resonance. AB - In the heart, detection of hyperpolarized [(13)C]bicarbonate and (13)CO(2) by magnetic resonance (MR) after administration of hyperpolarized [1-(13)C]pyruvate is caused exclusively by oxidative decarboxylation of pyruvate via the pyruvate dehydrogenase complex (PDH). However, liver mitochondria possess alternative anabolic pathways accessible by [1-(13)C]pyruvate, which may allow a wider diagnostic range for hyperpolarized MR compared with other tissue. Metabolism of hyperpolarized [1-(13)C]pyruvate in the tricarboxylic acid (TCA) cycle was monitored in the isolated perfused liver from fed and fasted mice. Hyperpolarized [1-(13)C]pyruvate was rapidly converted to [1-(13)C]lactate, [1-(13)C]alanine, [1 (13)C]malate, [4-(13)C]malate, [1-(13)C]aspartate, [4-(13)C]aspartate, and [(13)C]bicarbonate. Livers from fasted animals had increased lactate:alanine, consistent with elevated NADH:NAD(+). The appearance of asymmetrically enriched malate and aspartate indicated high rates of anaplerotic pyruvate carboxylase activity and incomplete equilibration with fumarate. Hyperpolarized [(13)C]bicarbonate was also detected, consistent with multiple mechanisms, including cataplerotic decarboxylation of [4-(13)C]oxaloacetate via phosphoenolpyruvate carboxykinase (PEPCK), forward TCA cycle flux of [4 (13)C]oxaloacetate to generate (13)CO(2) at isocitrate dehydrogenase, or decarboxylation of [1-(13)C]pyruvate by PDH. Isotopomer analysis of liver glutamate confirmed that anaplerosis was sevenfold greater than flux through PDH. In addition, signal from [4-(13)C]malate and [4-(13)C]aspartate was markedly blunted and signal from [(13)C]bicarbonate was completely abolished in livers from PEPCK KO mice, indicating that the major pathway for entry of hyperpolarized [1-(13)C]pyruvate into the hepatic TCA cycle is via pyruvate carboxylase, and that cataplerotic flux through PEPCK is the primary source of [(13)C]bicarbonate. We conclude that MR detection of hyperpolarized TCA intermediates and bicarbonate is diagnostic of pyruvate carboxylase and PEPCK flux in the liver. PMID- 22065780 TI - Genotypes of predomestic horses match phenotypes painted in Paleolithic works of cave art. AB - Archaeologists often argue whether Paleolithic works of art, cave paintings in particular, constitute reflections of the natural environment of humans at the time. They also debate the extent to which these paintings actually contain creative artistic expression, reflect the phenotypic variation of the surrounding environment, or focus on rare phenotypes. The famous paintings "The Dappled Horses of Pech-Merle," depicting spotted horses on the walls of a cave in Pech Merle, France, date back ~25,000 y, but the coat pattern portrayed in these paintings is remarkably similar to a pattern known as "leopard" in modern horses. We have genotyped nine coat-color loci in 31 predomestic horses from Siberia, Eastern and Western Europe, and the Iberian Peninsula. Eighteen horses had bay coat color, seven were black, and six shared an allele associated with the leopard complex spotting (LP), representing the only spotted phenotype that has been discovered in wild, predomestic horses thus far. LP was detected in four Pleistocene and two Copper Age samples from Western and Eastern Europe, respectively. In contrast, this phenotype was absent from predomestic Siberian horses. Thus, all horse color phenotypes that seem to be distinguishable in cave paintings have now been found to exist in prehistoric horse populations, suggesting that cave paintings of this species represent remarkably realistic depictions of the animals shown. This finding lends support to hypotheses arguing that cave paintings might have contained less of a symbolic or transcendental connotation than often assumed. PMID- 22065781 TI - Hypo- and hyperactivated Notch signaling induce a glycolytic switch through distinct mechanisms. AB - A switch from oxidative phosphorylation to glycolysis is frequently observed in cancer cells and is linked to tumor growth and invasion, but the underpinning molecular mechanisms controlling the switch are poorly understood. In this report we show that Notch signaling is a key regulator of cellular metabolism. Both hyper- and hypoactivated Notch induce a glycolytic phenotype in breast tumor cells, although by distinct mechanisms: hyperactivated Notch signaling leads to increased glycolysis through activation of the phosphatidylinositol 3-kinase/AKT serine/threonine kinase pathway, whereas hypoactivated Notch signaling attenuates mitochondrial activity and induces glycolysis in a p53-dependent manner. Despite the fact that cells with both hyper- and hypoactivated Notch signaling showed enhanced glycolysis, only cells with hyperactivated Notch promoted aggressive tumor growth in a xenograft mouse model. This phenomenon may be explained by that only Notch-hyperactivated, but not -hypoactivated, cells retained the capacity to switch back to oxidative phosphorylation. In conclusion, our data reveal a role for Notch in cellular energy homeostasis, and show that Notch signaling is required for metabolic flexibility. PMID- 22065782 TI - A yeast functional screen predicts new candidate ALS disease genes. AB - Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP 43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates similar to TDP-43 and FUS, followed by bioinformatics to predict prion-like domains in a subset of them. We sequenced one of these genes, TAF15, in patients with ALS and identified missense variants, which were absent in a large number of healthy controls. These disease-associated variants of TAF15 caused formation of cytoplasmic foci when expressed in primary cultures of spinal cord neurons. Very similar to TDP-43 and FUS, TAF15 aggregated in vitro and conferred neurodegeneration in Drosophila, with the ALS-linked variants having a more severe effect than wild type. Immunohistochemistry of postmortem spinal cord tissue revealed mislocalization of TAF15 in motor neurons of patients with ALS. We propose that aggregation-prone RNA-binding proteins might contribute very broadly to ALS pathogenesis and the genes identified in our yeast functional screen, coupled with prion-like domain prediction analysis, now provide a powerful resource to facilitate ALS disease gene discovery. PMID- 22065784 TI - Competition is a driving force in topographic mapping. AB - Topographic maps are the primary means of relaying spatial information in the brain. Understanding the mechanisms by which they form has been a goal of experimental and theoretical neuroscientists for decades. The projection of the retina to the superior colliculus (SC)/tectum has been an important model used to show that graded molecular cues and patterned retinal activity are required for topographic map formation. Additionally, interaxon competition has been suggested to play a role in topographic map formation; however, this view has been recently challenged. Here we present experimental and computational evidence demonstrating that interaxon competition for target space is necessary to establish topography. To test this hypothesis experimentally, we determined the nature of the retinocollicular projection in Math5 (Atoh7) mutant mice, which have severely reduced numbers of retinal ganglion cell inputs into the SC. We find that in these mice, retinal axons project to the anteromedialj portion of the SC where repulsion from ephrin-A ligands is minimized and where their attraction to the midline is maximized. This observation is consistent with the chemoaffinity model that relies on axon-axon competition as a mapping mechanism. We conclude that chemical labels plus neural activity cannot alone specify the retinocollicular projection; instead axon-axon competition is necessary to create a map. Finally, we present a mathematical model for topographic mapping that incorporates molecular labels, neural activity, and axon competition. PMID- 22065785 TI - Nanoparticles enhance brain delivery of blood-brain barrier-impermeable probes for in vivo optical and magnetic resonance imaging. AB - Several imaging modalities are suitable for in vivo molecular neuroimaging, but the blood-brain barrier (BBB) limits their utility by preventing brain delivery of most targeted molecular probes. We prepared biodegradable nanocarrier systems made up of poly(n-butyl cyanoacrylate) dextran polymers coated with polysorbate 80 (PBCA nanoparticles) to deliver BBB-impermeable molecular imaging probes into the brain for targeted molecular neuroimaging. We demonstrate that PBCA nanoparticles allow in vivo targeting of BBB-impermeable contrast agents and staining reagents for electron microscopy, optical imaging (multiphoton), and whole brain magnetic resonance imaging (MRI), facilitating molecular studies ranging from individual synapses to the entire brain. PBCA nanoparticles can deliver BBB-impermeable targeted fluorophores of a wide range of sizes: from 500 Da targeted polar molecules to 150,000-Da tagged immunoglobulins into the brain of living mice. The utility of this approach is demonstrated by (i) development of a "Nissl stain" contrast agent for cellular imaging, (ii) visualization of amyloid plaques in vivo in a mouse model of Alzheimer's disease using (traditionally) non-BBB-permeable reagents that detect plaques, and (iii) delivery of gadolinium-based contrast agents into the brain of mice for in vivo whole brain MRI. Four-dimensional real-time two-photon and MR imaging reveal that brain penetration of PBCA nanoparticles occurs rapidly with a time constant of ~18 min. PBCA nanoparticles do not induce nonspecific BBB disruption, but collaborate with plasma apolipoprotein E to facilitate BBB crossing. Collectively, these findings highlight the potential of using biodegradable nanocarrier systems to deliver BBB-impermeable targeted molecular probes into the brain for diagnostic neuroimaging. PMID- 22065786 TI - Low paternity skew and the influence of maternal kin in an egalitarian, patrilocal primate. AB - Levels of reproductive skew vary in wild primates living in multimale groups depending on the degree to which high-ranking males monopolize access to females. Still, the factors affecting paternity in egalitarian societies remain unexplored. We combine unique behavioral, life history, and genetic data to evaluate the distribution of paternity in the northern muriqui (Brachyteles hypoxanthus), a species known for its affiliative, nonhierarchical relationships. We genotyped 67 individuals (22 infants born over a 3-y period, their 21 mothers, and all 24 possible sires) at 17 microsatellite marker loci and assigned paternity to all infants. None of the 13 fathers were close maternal relatives of females with which they sired infants, and the most successful male sired a much lower percentage of infants (18%) than reported for the most successful males in other species. Our findings of inbreeding avoidance and low male reproductive skew are consistent with the muriqui's observed social and sexual behavior, but the long delay (>=2.08 y) between the onset of male sexual behavior and the age at which males first sire young is unexpected. The allocation of paternity implicates individual male life histories and access to maternal kin as key factors influencing variation in paternal--and grandmaternal--fitness. The apparent importance of lifelong maternal investment in coresident sons resonates with other recent examinations of maternal influences on offspring reproduction. This importance also extends the implications of the "grandmother hypothesis" in human evolution to include the possible influence of mothers and other maternal kin on male reproductive success in patrilocal societies. PMID- 22065783 TI - Role of donor genital tract HIV-1 diversity in the transmission bottleneck. AB - The predominant mode of HIV-1 infection is heterosexual transmission, where a genetic bottleneck is imposed on the virus quasispecies. To probe whether limited genetic diversity in the genital tract (GT) of the transmitting partner drives this bottleneck, viral envelope sequences from the blood and genital fluids of eight transmission pairs from Rwanda and Zambia were analyzed. The chronically infected transmitting partner's virus population was heterogeneous with distinct genital subpopulations, and the virus populations within the GT of two of four women sampled longitudinally exhibited evidence of stability over time intervals on the order of weeks to months. Surprisingly, the transmitted founder variant was not derived from the predominant GT subpopulations. Rather, in each case, the transmitting variant was phylogenetically distinct from the sampled locally replicating population. Although the exact distribution of the virus population present in the GT at the time of transmission cannot be unambiguously defined in these human studies, it is unlikely, based on these data, that the transmission bottleneck is driven in every case by limited viral diversity in the donor GT or that HIV transmission is solely a stochastic event. PMID- 22065787 TI - Profile of Eric F. Lambin. PMID- 22065788 TI - Malaria antifolate resistance with contrasting Plasmodium falciparum dihydrofolate reductase (DHFR) polymorphisms in humans and Anopheles mosquitoes. AB - Surveillance for drug-resistant parasites in human blood is a major effort in malaria control. Here we report contrasting antifolate resistance polymorphisms in Plasmodium falciparum when parasites in human blood were compared with parasites in Anopheles vector mosquitoes from sleeping huts in rural Zambia. DNA encoding P. falciparum dihydrofolate reductase (EC 1.5.1.3) was amplified by PCR with allele-specific restriction enzyme digestions. Markedly prevalent pyrimethamine-resistant mutants were evident in human P. falciparum infections- S108N (>90%), with N51I, C59R, and 108N+51I+59R triple mutants (30-80%). This resistance level may be from selection pressure due to decades of sulfadoxine/pyrimethamine use in the region. In contrast, cycloguanil-resistant mutants were detected in very low frequency in parasites from human blood samples S108T (13%), with A16V and 108T+16V double mutants (~4%). Surprisingly, pyrimethamine-resistant mutants were of very low prevalence (2-12%) in the midguts of Anopheles arabiensis vector mosquitoes, but cycloguanil-resistant mutants were highly prevalent-S108T (90%), with A16V and the 108T+16V double mutant (49-57%). Structural analysis of the dihydrofolate reductase by in silico modeling revealed a key difference in the enzyme within the NADPH binding pocket, predicting the S108N enzyme to have reduced stability but the S108T enzyme to have increased stability. We conclude that P. falciparum can bear highly host specific drug-resistant polymorphisms, most likely reflecting different selective pressures found in humans and mosquitoes. Thus, it may be useful to sample both human and mosquito vector infections to accurately ascertain the epidemiological status of drug-resistant alleles. PMID- 22065789 TI - Profile of Philip N. Johnson-Laird. PMID- 22065790 TI - CD83-stimulated monocytes suppress T-cell immune responses through production of prostaglandin E2. AB - CD83 is commonly known as a specific marker for mature dendritic cells. It has been shown to be important for CD4(+) T-cell development in the thymus. However, its function in the peripheral immune system remains enigmatic. Here, we show that CD83 inhibits proliferation and production of IL-2 and IFN-gamma by T cells, and the inhibitory effect of CD83 is mediated by monocytes. Prostaglandin E2 (PGE(2)), but not IL-10 or TGF-beta, was up-regulated specifically by CD83 in monocytes. Consistent with high levels of PGE(2), expression of COX-2 also was increased upon CD83 treatment. NF-kappaB activation also is required for induction of PGE(2) by CD83. Finally, application of the COX-2-selective inhibitor NS-398 fully prevented CD83-triggered inhibition of T-cell responses. Our study establishes an immune-regulatory mechanism by CD83 via stimulation of PGE(2) production in monocytes. PMID- 22065791 TI - IFN-alpha and CD46 stimulation are associated with active lupus and skew natural T regulatory cell differentiation to type 1 regulatory T (Tr1) cells. AB - Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptive immune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral tissues: thymus-developed natural T regulatory cells (nTregs) controlling self-tolerance and antiinflammatory IL-10-secreting type 1 regulatory T cells (Tr1) derived from Ag-stimulated T cells, which regulate inflammation-dependent adaptive immunity and minimize immunopathology. We establish herein that cell contact-mediated nTreg regulatory function is inhibited by inflammation, especially in the presence of the complement C3b receptor (CD46). Instead, as with other T-cell subsets, the latter inflammatory conditions of stimulation skew nTreg differentiation to Tr1 cells secreting IL 10, an effect potentiated by IFN-alpha. The clinical relevance of these findings was verified in a study of 152 lupus patients, in which we showed that lupus nTreg dysfunction is not due to intrinsic defects but is rather induced by C3b stimulation of CD46 and IFN-alpha and that these immune components of inflammation are directly associated with active lupus. These results provide a rationale for using anti-IFN-alpha Ab immunotherapy in lupus patients. PMID- 22065792 TI - Modulation of the feedback-related negativity by instruction and experience. AB - A great deal of research focuses on how humans and animals learn from trial-and error interactions with the environment. This research has established the viability of reinforcement learning as a model of behavioral adaptation and neural reward valuation. Error-driven learning is inefficient and dangerous, however. Fortunately, humans learn from nonexperiential sources of information as well. In the present study, we focused on one such form of information, instruction. We recorded event-related potentials as participants performed a probabilistic learning task. In one experiment condition, participants received feedback only about whether their responses were rewarded. In the other condition, they also received instruction about reward probabilities before performing the task. We found that instruction eliminated participants' reliance on feedback as evidenced by their immediate asymptotic performance in the instruction condition. In striking contrast, the feedback-related negativity, an event-related potential component thought to reflect neural reward prediction error, continued to adapt with experience in both conditions. These results show that, whereas instruction may immediately control behavior, certain neural responses must be learned from experience. PMID- 22065793 TI - 2-(4-Bromo-phen-yl)-3,4-dihydro-isoquinolin-2-ium thio-cyanate hemihydrate. AB - In the title hemihydrated salt, C(15)H(13)BrN(+).NCS(-).0.5H(2)O, the two benzene rings are aligned at a dihedral angle of 46.9 (1) degrees . The six-membered heterocycle of the dihydro-isoquinoline unit adopts a half-chair conformation. The water mol-ecule and thio-cyanate ion are linked by O-H?N hydrogen bonds, generating a four-membered ring motif. In addition, C-H?O and C-H?S inter-actions link the components into a chain along the c axis. pi-pi inter-actions [centroid centroid distance = 3.974 (2) A] link the chains into sheets and further pi-pi [centroid-centroid distance = 3.746 (2) A] and C-H?pi inter-actions give rise to a three-dimensional nework. PMID- 22065794 TI - Dichloridobis[4-(1H-pyrazol-3-yl)pyridine-kappaN]zinc. AB - In the title compound, [ZnCl(2)(C(8)H(7)N(3))(2)], the Zn(II) cation is coordinated by two Cl(-) anions and two 4-(1H-pyrazol-3-yl)pyridine ligands in a distorted tetra-hedral geometry. In the two 4-(1H-pyrazol-3-yl)pyridine ligands, the dihedral angles between the pyrazole and pyridine rings are 3.3 (3) and 13.3 (3) degrees . Inter-molecular N-H?N and N-H?Cl hydrogen bonding is present in the crystal structure. PMID- 22065795 TI - Utility of thyroid collars in cephalometric radiography. AB - OBJECTIVE: A study was carried out to investigate the rationale that use of a thyroid collar (TC) in cephalometric radiography hampers the diagnostic and descriptive quality of lateral cephalogram. METHODS: A randomized observer blinded study was designed. The study consisted of two groups. The first group data were retrieved from the oral radiology archival system having lateral cephalogram without a TC. The second group was selected from the oral radiology department of patients where lateral cephalogram was taken using a TC. Lateral cephalogram was taken on direct digital system, the Kodak 9000 unit (Eastman Kodak, Rochester, NY). 2 observers blinded about the aim of the study were appointed to identify 15 sets of landmarks on the lateral cephalogram. Interobserver variance was also analysed for the study. RESULTS: 50 lateral cephalograms in each group were studied. Out of 15 sets of landmarks, 12 were identified consistent with the TC group. Three landmarks, namely the hyoid bone, second cervical vertebra and third cervical vertebra could not be identified on the TC group. There was no significant difference in the interobserver markings on lateral cephalogram. CONCLUSIONS: TCs do mask a few landmarks on the lateral cephalogram. These landmarks are mainly used for analysis of skeletal maturity index (SMI). Lead TCs are probably the most convenient and easily available means to protect the thyroid from unwanted radiation while taking lateral cephalogram. It is therefore encouraged to use a TC during routine cephalometric radiography where SMI information is not needed. PMID- 22065796 TI - A prospective study of three diagnostic sonographic methods in differentiation between benign and malignant salivary gland tumours. AB - OBJECTIVE: The aim of this study was to evaluate the role of three diagnostic sonographic methods, greyscale sonography (GSS), colour Doppler sonography (CDS) and spectral Doppler (SPD), in differentiating between benign and malignant salivary gland (SG) tumours. METHODS: 44 patients with SG masses were examined using GSS, CDS and SPD. The morphological features of each tumour were evaluated using GSS, the distribution and number of detected blood vessels were assessed using CDS, and peak systolic velocity (PSV), resistive index (RI) and pulsatility index (PI) were measured on SPD. All cases underwent excisional biopsy and a definite tissue diagnosis was obtained. RESULTS: Histopathological examination revealed that 28 of the 44 tumours were benign and 16 were malignant. GSS showed that malignant SG tumours had a significantly higher incidence of ill-defined borders and lymph node involvement than benign tumours, but there was no significant difference between benign and malignant SG tumours regarding echogenicity, homogeneity or sonographic shape. CDS demonstrated malignant tumours with significantly higher vascularity and a scattered distribution. Using SPD, malignant tumours had significantly higher PSV, RI and PI compared with benign tumours. CONCLUSION: RI values above 0.7, PI values above 1.2, PSV values above 44.3 cm s(-1), ill-defined borders, lymph node involvement, Grade 2 or 3 vascularity and hilar distribution of blood vessels should alert the clinician to suspect a malignant SG tumour. After consensus on the threshold values of PSV, RI and PI in differentiating benign from malignant SG tumours, these numbers should be incorporated into the software of ultrasound machines to guide the sonographer in his or her analysis. PMID- 22065797 TI - Comparison of ultrasonography with computed tomography in the diagnosis of nasal bone fractures. AB - OBJECTIVES: The aim of this study is to compare ultrasonography with CT in the diagnosis of nasal bone fractures. METHODS: 40 patients (9 female and 31 male) with mid-facial fractures, which were suspected nasal bone fractures, were included. All of the patients had mid-facial CT images. Ultrasonography with a 7.5 MHz transducer (Aloka 3500, Tokyo, Japan) was used to evaluate the nasal bone fractures. All of the sonograms were compared with CT findings for sensitivity, specificity and predictive values. A chi(2) test was applied to the data to assess statistical significance. RESULTS: CT diagnosed nasal bone fractures in 24 of the 40 patients (9 unilateral fractures and 15 bilateral fractures) while ultrasonography diagnosed the fractured bones in 23 patients (9 unilateral fractures and 14 bilateral fractures). Ultrasonography missed one fractured bone in a bilateral fractured case and a unilateral fracture was also missed (two false-negative results). The sensitivity and specificity of ultrasonography in assessing nasal bone fracture in comparison with CT were 94.9% and 100%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) of ultrasonographic evaluation of the nasal bone fractures were 100% and 95.3%, respectively. The chi(2) test did not show any significant difference between CT and ultrasonography in diagnosis of nasal bone fractures (P = 0.819). CONCLUSION: Ultrasonography can be used as a first line of diagnostic imaging for evaluating nasal bone fractures, especially in children and pregnant women. PMID- 22065798 TI - Comparison of linear and angular measurements using two-dimensional conventional methods and three-dimensional cone beam CT images reconstructed from a volumetric rendering program in vivo. AB - OBJECTIVE: The aim of this study was to compare the linear and angular measurements made on two-dimensional (2D) conventional cephalometric images and three-dimensional (3D) cone beam CT (CBCT) generated cephalograms derived from a 3D volumetric rendering program. METHODS: Pre-treatment cephalometric digital radiographs of 11 patients and their corresponding CBCT images were randomly selected. The digital cephalometric radiographs were traced using Vista Dent OC (GAC International, Inc Bohemia, NY) and by hand. CBCT and Maxilim(r) (Medicim, Sint-Niklass, Belgium) software were used to generate cephalograms from the CBCT data set that were then linked to the 3D hard-tissue surface representations. In total, 16 cephalometric landmarks were identified and 18 widely used measurements (11 linear and 7 angular) were performed by 2 independent observers. Intraobserver reliability was assessed by calculating intraclass correlation coefficients (ICC), interobserver reliability was assessed with Student t-test and analysis of variance (ANOVA). Mann-Whitney U-tests and Kruskal-Wallis H tests were also used to compare the three methods (P < 0.05). RESULTS: The results demonstrated no statistically significant difference between interobserver analyses for CBCT-generated cephalograms (P < 0.05), except for Gonion-Menton (Go Me) and Condylion-Gnathion (Co-Gn). Intraobserver examinations showed low ICCs, which was an indication of poor reproducibility for Go-Me and Sella-Nasion (S-N) in CBCT-generated cephalograms and poor reproducibility for Articulare-Gonion (Ar Go) in the 2D hand tracing method (P < 0.05). No statistical significance was found for Vista Dent OC measurements (P > 0.05). CONCLUSIONS: Measurements from in vivo CBCT-generated cephalograms from Maxilim(r) software were found to be similar to conventional images. Thus, owing to higher radiation exposure, CBCT examinations should only be used when the inherent 3D information could improve the outcome of treatment. PMID- 22065799 TI - Fractal dimension evaluation of cone beam computed tomography in patients with bisphosphonate-associated osteonecrosis. AB - OBJECTIVES: The aim of this study was to (1) evaluate the fractal dimension (FD) in regions of the mandible on cone beam CT (CBCT) images of patients with bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) and (2) to select the most suitable region of interest (ROI) for further study on detection of bone alterations associated with bisphosphonates. METHODS: CBCT images of patients with BP-ONJ were included with matched controls. Values of FD were compared between groups. Selected ROIs were: ROI-1 - below the mandibular foramen; ROI-2 - above the mandibular foramen; ROI-3 - anterior to the mental foramen; ROI-4 - above the mandibular canal. The area of bone exposure was included as ROI-5. The results were analysed using generalized estimating equations and conditional logistic regression. RESULTS: There were 36 patients (67% female) with a mean age of 60.7 years. The mean FDs were: ROI-1 - 1.678 for controls and 1.673 for patients (P = 0.81); ROI-2 - 1.657 for controls and 1.653 for patients (P = 0.78); ROI-3 - 1.661 for controls and 1.684 for patients (P = 0.17); and ROI-4 1.670 for controls and 1.698 for patients (P = 0.03). The value of the FD in the area of exposed bone was the highest (1.729). The odds of being a BP-ONJ patient vs being a control was six times as high for individuals with a higher FD score at ROI-4, although the confidence interval was quite wide owing to the small sample size. CONCLUSION: In this preliminary study, BP-ONJ patients had higher FD values than controls at regions close to the alveolar process. The results suggest that FD is a promising tool for detection of bone alterations associated with BP-ONJ. PMID- 22065800 TI - A suggested technique for the application of the cone beam computed tomography periapical index. AB - OBJECTIVES: Cone beam CT (CBCT) produces undistorted three-dimensional (3D) images of the maxillofacial region with a radiation dosage lower than conventional CT. The periapical index score (PAI) is commonly used to follow up the lesions in the bone using periapical radiographs. Recently, a new PAI based on CBCT was introduced (CBCT-PAI). The aim of this technical report is to present a modified reproducible method to assess the CBCT-PAI. METHODS: CBCT was used to evaluate a periapical bone lesion observed in the area of tooth number 13 before treatment and 2 years after treatment. The modified CBCT-PAI was applied to both the examinations to measure the lesion. The dimensional analysis of the lesion was performed in each plane, assessing three fixed and reproducible dimensions: mesiodistal (M-D), buccolingual (B-L) and coronoapical (C-A). The images were evaluated by three mutually independent examiners. Data were collected and reported in a chart. The results were compared with each other and with the PAI score from the periapical radiographs. RESULTS: The three observers reported the same measurements of the lesion for each plane. The CBCT-PAI follow-up showed a reduction of the size of the lesion (5D vs 4D) but also an increase in the erosion of the buccal cortical plate. The comparison of CBCT-PAI with classic PAI showed the first method to be more precise. CONCLUSIONS: This technical report shows how the CBCT-PAI can be applied to the CBCT exam of a periapical lesion in a reproducible way. PMID- 22065801 TI - Abnormal radiological features in a multiple myeloma patient: a case report and radiological review of myelomas. AB - Multiple myeloma is the prototype of malignant monoclonal gammopathies. The most common skeletal sites are pelvis, skull, spine, ribs and femoral and humeral shafts. The classic radiographic presentation of multiple myeloma is lytic skeletal lesions. Other types of presentation include sclerotic and porotic changes. Primary sclerotic manifestations are rare and occur in only 3% of cases. Although exceptional, multiple myeloma must be borne in mind in the presence of bone sclerosis. This report presents a patient with multiple myeloma with a sunburst/hair-on-end pattern on the radiograph and sclerotic skeletal lesions. PMID- 22065802 TI - Cone beam CT sialography of Stafne bone cavity. AB - Stafne bone cavity (SBC) was mostly described as a small oval radiolucency in the posterior mandibular region. To the best of our knowledge, the literature does not contain any report of the use of cone beam CT (CBCT) sialography for the diagnosis of this entity. The aim of this paper is to present a large, irregular and expanded atypical SBC, which made diagnosis difficult. A CBCT sialography was performed to get a definite diagnosis of this rare entity. PMID- 22065803 TI - Tetrafid mandibular condyle: a unique case report and review of the literature. AB - Morphological changes such as bifid and trifid mandibular condyle are rare entities. The aim of the present report is to describe a unique morphological variation of the mandibular condyle which has four separate condylar heads (tetrafid mandibular condyle) and to discuss clinical and radiological differential diagnosis of tetrafid mandibular condyle with advanced imaging techniques. PMID- 22065804 TI - Worth syndrome as a diagnosis for mandibular osteosclerosis. AB - This case report presents an unusual incidental radiographic finding on a dental panoramic radiograph that caused diagnostic confusion. A 46-year-old female presented with symmetrical sclerotic cortical thickening of the anterior mandible visible on radiograph, with no other major clinical examination findings. The patient subsequently showed no change in radiographic appearance over a 6 year period. Based on this evidence, and the benign nature of the history, we propose a diagnosis of Worth syndrome. This report aims to clarify the difference in terminology and presentation of two conditions known to produce mandibular osteosclerosis: Worth syndrome and Van Buchem disease, both of which are often quoted synonymously in the literature. PMID- 22065805 TI - Spontaneous regression of large mandibular lesions: consider Langerhans cell histiocytosis. PMID- 22065806 TI - An interesting artefact! PMID- 22065809 TI - 1H-1,2,4-Triazol-4-ium 4-nitro-benzene-sulfonate monohydrate. AB - In the 4-nitro-benzene sulfonate anion of the title compound, C(2)H(4)N(3) (+).C(6)H(4)NO(5)S(-).H(2)O, the nitro group is slightly twisted from the plane of the benzene ring [dihedral angle = 2.8 (3) degrees ]. In the crystal, the three components are linked via N-H?O, O-H?N, O-H?O and C-H?O hydrogen bonds, forming a two-dimensional network parallel to the bc plane. A short inter molecular O?N contact of 2.872 (3) A is also observed between the nitro and sulfonate groups. PMID- 22065810 TI - Diethyl 4,4'-(diazenediyl)dibenzoate. AB - The full mol-ecule of the title compound, C(18)H(18)N(2)O(4), is generated by the application of an inversion centre. There are strong pi-pi inter-actions between adjacent mol-ecules with a centroid-centroid distance of 3.298 (2)A. PMID- 22065811 TI - 1,3-Benzothia-zole-oxalic acid (2/1). AB - The asymmetric unit of the title compound, C(7)H(5)NS.0.5C(2)H(2)O(4), contains one benzothia-zole mol-ecule and half an oxalic acid mol-ecule, the complete mol ecule being generated by inversion symmetry. The benzothia-zole mol-ecule is essentially planar, with a maximum deviation of 0.007 (1) A. In the crystal, the benzothia-zole mol-ecules inter-act with the oxalic acid mol-ecules via O-H?N and C-H?O hydrogen bonds generating R(2) (2)(8) (* 2) and R(4) (4)(10) motifs, thereby forming supra-molecular ribbons along [101]. PMID- 22065812 TI - (E)-2-[4-(2-Chloro-phen-yl)but-3-en-2-yl-idene]malononitrile. AB - There are two independent but virtually identical mol-ecules in the asymmetric unit of the title compound, C(13)H(19)ClN(2). Each mol-ecular skeleton displays an approximately planar structure except for the methyl group [the r.m.s. deviations for all 16 non-H atoms are 0.039 (mol-ecule 1) and 0.056 A (mol-ecule 2)]. An E configuration is found about each of the C=C bonds. The crystal packing is stabilized by C-H?N inter-actions that connect the independent mol-ecules into supra-molecular chains along the c-axis direction. PMID- 22065813 TI - (E)-1-(3-Nitro-phen-yl)ethanone (2-methyl-phen-yl)hydrazone. AB - In the title Schiff base compound, C(15)H(15)N(3)O(2), the azomethine double bond adopts an E configuration. The dihedral angle between the two aromatic rings is 13.4 (12) degrees . In the crystal, mol-ecules are arranged in wave-like layers parallel to (100) without any classical hydrogen bonding. PMID- 22065814 TI - Diethyl [benzyl-amino-(1,3-diphenyl-1H-pyrazol-4--yl)meth-yl]phospho-nate. AB - In the title compound, C(27)H(30)N(3)O(3)P, the pyrazole ring is essentially planar [maximum deviation = 0.002 (2) A] and it forms dihedral angles of 9.3 (1) and 40.2 (1) degrees , respectively, with the phenyl rings attached to the N and C atoms. In the crystal, pairs of centrosymmetrically related mol-ecules are linked into dimers by N-H?O hydrogen bonds. PMID- 22065815 TI - A monoclinic polymorph of dichlorido(2,4,6-tri-2-pyridyl-1,3,5-triazine kappaN,N,N)manganese(II). AB - The Mn(II) ion in the title complex, [MnCl(2)(C(18)H(12)N(6))], is five coordinated in a distorted square-pyramidal geometry by three N atoms of the tridentate 2,4,6-tri-2-pyridyl-1,3,5-triazine ligand and two chloride anions. In the crystal, the pyridyl rings are located approximately parallel to their carrier triazine ring, making dihedral angles of 5.0 (1), 3.8 (1) and 3.2 (1) degrees . Intramolecular C-H?N hydrogen bonds are present. The complexes are stacked in columns along the c axis and linked by inter-molecular C-H?Cl hydrogen bonds, forming one-dimensional chains. In the column, inter-molecular pi-pi inter actions between the six-membered rings are present, the shortest centroid centroid distance being 3.623 (2) A. The structure reported herein represents a monoclinic polymorph of the previously reported triclinic form [Ha (2010 ?). Acta Cryst. E66, m262]. PMID- 22065816 TI - {2,2'-[(2,2-Dimethyl-propane-1,3-diyl-dinitrilo)-bis-(phenyl-methyl-idyne)] diphenolato}nickel(II). AB - The asymmetric unit of the title complex, [Ni(C(31)H(28)N(2)O(2))], comprises two crystallographically independent mol-ecules. The geometry around the Ni(II) atom in each mol-ecule is distorted square planar. The dihedral angles between the two phen-oxy rings in each mol-ecule are 17.8 (4) and 36.5 (4) degrees . The crystal packing is stabilized by weak pi-pi inter-actions [centroid-centroid distance = 3.758 (5) A] and C-H?pi inter-actions. PMID- 22065817 TI - 4,4'-Dichloro-2,2'-[imidazolidine-1,3-diylbis(methylene)]diphenol. AB - The imidazolidine ring in the title compound, C(17)H(18)Cl(2)N(2)O(2), adopts a twist conformation. The observed conformation is stabilized by two intra molecular O-H?N hydrogen bonds, with both N atoms acting as hydrogen-bond acceptors. The phenyl substituents are aligned at 70.0 (1) and 76.6 (1) degrees with respect to the best plane through the five atoms of the imidazolidine ring. Weak inter-molecular C-H?O inter-actions stabilize the crystal packing. PMID- 22065818 TI - Hexaaqua-magnesium bis-(3-carb-oxy-4-hy-droxy-benzene-sulfonate) dihydrate. AB - In the crystal structure of the title compound, [Mg(H(2)O)(6)](C(7)H(5)O(6)S)(2).2H(2)O, the octa-hedral complex cation lies on an inversion centre and is hydrogen bonded through the coordinated water molecules to the substituted benzene-sulfonate monoanions and the water mol ecules of solvation. These inter-actions together with a carb-oxy-lic acid O H?O(sulfonate) association give a three-dimensional structure. PMID- 22065819 TI - 2-(2-Pyrid-yl)pyridinium (2,2'-bipyridine-kappaN,N')tetra-kis-(nitrato kappaO,O')bis-muthate(III). AB - The structure of the title compound, (C(10)H(9)N(2))[Bi(NO(3))(4)(C(10)H(8)N(2))], consists of 2-(2-pyrid yl)pyridinium cations and anions [Bi(NO(3))(4)(C(10)H(8)N(2))](-). The Bi(3+) ion lies on the twofold axis. It is coordinated by two nitro-gen atoms from one 2,2' bipyridine ligand and eight oxygen atoms from four NO(3) (-) anions. The disordered cation is positioned at the inversion centre. The [Bi(NO(3))(4)(C(10)H(8)N(2))](-) anions and 2-(2-pyrid-yl)pyridinium cations are connected via N-H?O hydrogen bonds into chains. Moreover, these chains are further linked into a two-dimensional layered structure through pi-pi stacking inter-actions between bipyridine ligands along the c axis [centroid-centroid distance = 2.868 (4) A]. PMID- 22065820 TI - Ovarian hyperstimulation syndrome. AB - Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of assisted reproduction technology. The syndrome is characterized by cystic enlargement of the ovaries and a fluid shift from the intravascular to the third space due to increased capillary permeability and ovarian neoangiogenesis. Its occurrence is dependent on the administration of human chorionic gonadotrophin (hCG). beta-hCG and its analogs, estrogen, estradiol, prolactin, histamine and prostaglandins have all been implicated in OHSS but now it is increasingly better understood that the vasoactivesubstances such as interleukins, tumor necrosis factor-alpha, endothelin-1, and vascular endothelial growth factor (VEGF) secreted by the ovaries have been implicated in increasing vascular permeability. Enlargement of the ovaries causes abdominal pain, nausea and vomiting. Leakage of fluid from follicles, increased capillary permeability leading to third spacing (due to the release of vasoactive substances), or frank rupture of follicles can all cause ascites. Due to leakage of fluid through the impaired blood vessels both within and outside the ovary there is massive fluid-shift from the intra vescular bed to the third compartment results in intravascular hypovolemia with concomitant development of edema, ascites, hydrothorax and/or hydropericardium. Low-dose gonadotrophin protocols have been implemented to reduce the risks of fertility treatment in polycystic ovary syndrome patients. Prophylactic albumin administration may interrupt the development of OHSS by increasing the plasma oncotic pressure and binding mediators of ovarian origin. OHSS is significantly lower in an antagonist protocol than in an agonist protocol. Cabergoline inhibits partially the VEGF receptor 2 phosphorylation levels and associated vascular permeability without affecting luteal angiogenesis reduces the 'early' (within the first 9 days after hCG) onset of OHSS. To prevent thrombosis, subcutaneous heparin 5000-7500 U/d is begun on the first day of admission. These patients need a hospital ward where the clinical picture is well understood and the personnel have expertise in its treatment and follow-up. Admission to an intensive care unit is necessary when critical OHSS develops. PMID- 22065821 TI - Subglottic stenosis following percutaneous tracheostomy: a single centre report as a descriptive study. AB - Tracheal stenosis is a potential complication of tracheostomy. The present study aimed to describe the epidemiologic profile of subglottic stenosis in a referral medical centre. During a 4-year period, all patients who had been admitted in an Intensive Care Unit of Imam Khomeini Hospital (affiliated to Tehran University of Medical Sciences) and had undergone percutaneous tracheostomy during 7-10 days after endotracheal intubation were enrolled in the study. After removing the tracheostomy tube, patients were evaluated regarding development of tracheal stenosis using fiberoptic bronchoscopy and multi-slice computed tomography scan. During the study period, percutaneous tracheostomy was performed in 140 patients with a mean age of 38 years. Overall 54 patients died due to the severity of the disorder during hospitalization. In the remaining 86 patients, 54 cases needed permanent or long-term mechanical ventilation and were excluded from the study. Twelve patients died during the first 3 months and 20 patients were left for final assessment. Multi-slice computed tomography scan imaging showed subglottic stenosis in 17 cases (85%). Of these, 9 patients (52%) had tracheal stenosis of < 50%. Tracheal stenosis of 25- 40% was found in 5 cases (25%). Patients in whom the tracheostomy tube had been removed in the first 3 weeks after tracheostomy did not present tracheal stenosis (n = 3, 15%). The present study revealed that subglottic stenosis is frequent in patients who have undergone percutaneous tracheostomy in the Intensive Care unit setting. However, the stenosis is generally mild and is not associated with serious and/ or life-threatening clinical manifestations. PMID- 22065822 TI - Ethyl-enediammonium tetra-aqua-disulfato-cadmate. AB - The crystal structure of the title compound, [NH(3)(CH(2))(2)NH(3)][Cd(SO(4))(2)(H(2)O)(4)], consists of [Cd(SO(4))(2)(H(2)O)(4)](2-) anions that are built from octa-hedral Cd(H(2)O)(4)O(2) and SO(4) tetra-hedral units linked by corner sharing. The ethyl ene-diamminium cations are linked to the anions via N-H?O hydrogen bonds. The asymmetric unit contains one-half of the compound, the other half being related to the first by an inversion centre. The crystal structure presents alternate stacking of the inorganic and organic layers along the crystallographic b axis. The structure cohesion and stability is further assured by O(water)-H?O hydrogen bonds. PMID- 22065823 TI - Tetra-MU-acetato-kappaO:O'-bis-[(3,5-di-methyl-1H-pyrazole-kappaN)-copper(II)]. AB - The dinuclear centrosymmetric title compound, [Cu(2)(CH(3)CO(2))(4)(C(5)H(8)N(2))(2)], has a distorted square-pyramidal coordination geometry around each Cu(II) atom in which four O atoms from the bridging acetate ligands form the basal plane while two N atoms from the pyrazole ligands occupy the apical positions. The crystal has two half mol-ecules in the asymmetric unit with a Cu?Cu distance of 2.6762 (4) A. Disorder was found for two O atoms and two C atoms of one acetate ligand and refined with occupancies of 0.265 (7) and 0.735 (7). The crystal also features mol-ecules linked through two N-H?O hydrogen bonds resulting in one-dimensional chains extending along the crystallographic b axis. PMID- 22065824 TI - Lithium cobalt(II) pyrophosphate, Li(1.86)CoP(2)O(7), from synchrotron X-ray powder data. AB - Structure refinement of high-resolution X-ray powder diffraction data of the title compound gave the composition Li(1.865)CoP(2)O(7), which is also verified by the ICP measurement. Two Co sites exist in the structure: one is a CoO(5) square pyramid and the other is a CoO(6) octa-hedron. They share edges and are further inter-connected through P(2)O(7) groups, forming a three-dimensional framework, which exhibits different kinds of inter-secting tunnels containing Li cations and could be of great inter-est in Li ion battery chemistry. The structure also exhibits cation disorder with 13.5% Co residing at the lithium (Li1) site. Co seems to have an average oxidation state of 2.135, as obtained from the strutural stochiometry that closely supports the magnetic susceptibility findings. PMID- 22065825 TI - Deacetyl-nomilin monohydrate. AB - In the title compound (systematic name 1-hy-droxy-1,2-dihydro-obacunoic acid 3,4 lactone monohydrate), C(26)H(32)O(8).H(2)O, the dihedral angles between the planes of the ester groups and the furan plane are 43.06 (12) and 56.06 (7) degrees , while that between the furan plane and the keto group is 58.50 (9) degrees . The A/B, B/C and C/D ring junctions are all trans-fused. Inter molecular O-H?O hydrogen bonds between the hy-droxy and carbonyl groups and the water mol-ecule give rise to a three-dimensional structure. PMID- 22065826 TI - Bis(triphenyl-phosphanyl-idene)iminium dichloridotriphenyl-stannate(IV). AB - The structure of the title compound, [Ph(3)P=N=PPh(3)](+)[Ph(3)SnCl(2)](-) or (C(36)H(30)NP(2))[Sn(C(6)H(5))(3)Cl(2)], obtained as a by product of the reaction between Ph(3)SnCl and [Ph(3)P=N=PPh(3)](+).HSeO(3) (-), consists of discrete essentially isolated ions. Both the cation and the anion lie on twofold axes which pass through the central N atom in the cation and through the Sn(IV) atom in the anion. In the crystal, the ions inter-act only through a weak inter-action between the Cl atom of the anion and an H atom of a phenyl ring of the cation. PMID- 22065827 TI - 4,4'-[p-Phenyl-enebis(-oxy)]dibutanoic acid. AB - The complete mol-ecule of the title compound, C(14)H(18)O(6), has a center of inversion at the centroid of the benzene ring and the asymmetric unit contains one half-mol-ecule. The conformation of the side chain is anti [C-C-C-C = -171.40 (17) degrees ]. In the crystal, pairs of head-to-head carb-oxy-lic acid O-H?O hydrogen bonds link the mol-ecules into infinite zigzag chains propagating along [130]. Weak C-H?pi inter-actions between adjacent chains expand the structure into a layered network in the ac plane. PMID- 22065828 TI - 3-(3-Chloro-phenyl-sulfon-yl)-2,5-dimethyl-1-benzofuran. AB - In the title molecule, C(16)H(13)ClO(3)S, the 3-chloro-phenyl ring makes a dihedral angle of 76.30 (5) degrees with the mean plane of the benzofuran fragment. In the crystal, pairs of inter-molecular C-H?pi inter-actions link the mol-ecules into inversion dimers. PMID- 22065829 TI - 2,9-Dichloro-6H,13H-5:12,7:14-di-methano-dibenzo[d,i][1,3,6,8]tetra-azecine. AB - The title compound, C(16)H(14)Cl(2)N(4), is isomorphous with 2,9-dimethyl-6H,13H 5:12,7:14-dimethano-dibenzo[d,i]-[1,3,6,8]tetra-azecine [Rivera et al. (2009 ?). Acta Cryst. E65, o2553] and has twofold symmetry, with two carbon atoms located on a twofold axis. Only van der Waals forces occur between molecules in the crystal. In the isomorphous compound the crystal structure is stabilized by weak C-H?pi inter-actions. PMID- 22065830 TI - (E)-N'-(3-Bromo-5-chloro-2-hy-droxy-benzyl-idene)nicotinohydrazide. AB - There are two independent mol-ecules in the asymmetric unit of the title compound, C(13)H(9)BrClN(3)O(2), in which the dihedral angles between the benzene and pyridine rings are 8.23 (9) degrees and 52.84 (12) degrees . Both the mol ecules exist in an E configuration with respect to the C=N double bond. The two mol-ecules in the asymmetric unit are linked via weak C-H?O hydrogen bonds. In both the mol-ecules, an intra-molecular O-H?N hydrogen bond generate an S(6) graph-set motif. In the crystal, inter-molecular N-H?O and C-H?O hydrogen bonds generate bifurcated R(1) (2)(7) ring motifs. The crystal packing is further stabilized by weak inter-molecular N-H?O, N-H?N, C-H?O and pi-pi [centroid centroid distance 3.615 (2) A] inter-actions. PMID- 22065831 TI - Minimally-invasive parathyroid surgery. AB - During the last two decades, several techniques for minimally-invasive parathyroidectomy have been developed, including open approaches (open minimally invasive parathyroidectomy - OMI P), minimally-invasive radio-guided parathyroidectomy (MI-RP), video-assisted parathyroidectomy (VAP), video-assisted parathyroidectomy through a lateral approach (VAP-LA) and purely endoscopic parathyroidectomy (EP). We have reviewed the pertinent literature, analyzing the indications, outcomes, advantages and disadvantages of the different techniques. Even if the field of minimally-invasive parathyroidectomy is heterogeneous, there is some evidence that minimally-invasive video-assisted parathyroidectomy (MIVAP) should be preferred over OMIP for better cosmetic outcomes, improved visualization of neck structures and control of pain. There is also low-level evidence that MIVAP has some advantages over other purely endoscopic procedures for parathyroidectomy and VAP-LA, in terms of technical difficulties, in addition to the possibility to perform bilateral exploration and associated procedures on the thyroid gland. While the data on medium-term results are encouraging, longer follow-up times are still needed to confirm its safety and rate of cure with respect to conventional surgery. It has been demonstrated that MIVAP is also feasible in secondary and familial hyperparathyroidism, although no conclusive data are available. PMID- 22065832 TI - An evaluation of the effect of infertility on marital, sexual satisfaction indices and health-related quality of life in women. AB - BACKGROUND: The effect of infertility on marital and sexual functioning, health related quality of life (QoL) and the acceptability of the treatment modalities is a poorly researched area in India. AIMS AND OBJECTIVES: To measure and compare the impact of infertility on marital adjustment, sexual functioning, QoL and the acceptability of various treatment modalities in infertility. DESIGN AND SETTING: Hospital-based cross-sectional controlled study. MATERIALS AND METHODS: Data regarding infertility, socio-demographic characteristics and treatment acceptability was obtained via a semi-structured questionnaire. validated, standardized scales were used to measure marital adjustment (abbreviated dyadic adjustment scale), sexual functioning (abbreviated sexual functioning questionnaire) in cases and controls, and quality of life (FertiQol) in cases. Data from 106 women attending tertiary infertility centers who met the definition of primary infertility and 212 controls attending the medical outpatient department in the same centers was obtained. RESULTS: Body mass index and socioeconomic status were significant (P < 0.006 and < 0.0001 respectively) for infertility. Fertility-enhancing regimens and adoption had the highest acceptability with a wide dispersion of range for adoption and least acceptance for sperm, egg, embryo donation and surrogate motherhood. Logistic regression analysis revealed a significant effect size of infertility on marital adjustment (Nagelkerke R(2) 0.725, Cohen's D 0.86) and sexual functioning (Nagelkerke R(2) 0.73, Cohen's D 0.815). QoL showed a decrease in mean scores on the FertiQol scale similar to normative data. CONCLUSIONS: Effective counseling, reassurance and measures to reduce the impact of the condition on marital and sexual life, overall QoL are needed to impart a holistic treatment in infertility. PMID- 22065833 TI - Propyl 3-oxo-2,3-dihydro-1,2-benzothia-zole-2-carboxyl-ate. AB - The title compound, C(11)H(11)NO(3)S, was synthesized by the reaction of benzo[d]isothia-zol-3(2H)-one with propyl carbono-chloridate in toluene. The benzoisothiazolone ring system is approximately planar with a maximum deviation from the mean plane of 0.0226 (14) A for the N atom. Weak inter-molecular C-H?O hydrogen bonding occurs in the crystal structure. PMID- 22065834 TI - 4,4'-Dimeth-oxy-2,2'-{[(3aRS,7aRS)-2,3,3a,4,5,6,7,7a-octa-hydro-1H-1,3 benzimidazole-1,3-diyl]bis(methyl-ene)}diphenol. AB - The title compound, C(23)H(30)N(2)O(4), is a Mannich base useful for studying the effect of an electron-donating phenol substituent on intra-molecular hydrogen bonding. In the mol-ecular structure, the cyclo-hexane ring adopts a chair conformation and the five-membered ring has a twisted envelope conformation. Each meth-oxy group is oriented in the same plane of the respective aromatic ring, showing torsion angles below 11.8 (3) degrees and bond angles between the meth oxy group and the aromatic ring of 116.6 (2) and 116.6 (1) degrees . The structure shows inter-actions between two the N atoms of the heterocyclic ring and the hy-droxy groups by intra-molecular O-H?N hydrogen-bonding inter-actions. In the crystal, C-H?O inter-actions are observed. The crystal studied was a racemic mixture of RR and SS enanti-omers. PMID- 22065835 TI - (2E)-1-(Pyridin-2-yl)-3-(2,4,6-trimeth-oxy-phen-yl)prop-2-en-1-one. AB - The title heteroaryl chalcone derivative, C(17)H(17)NO(4), is a condensation product of 2-acetyl-pyridine and 2,4,6-trimeth-oxy-benzaldehyde. The mol-ecule is roughly planar, the dihedral angle between the pyridine and benzene rings being 5.51 (10) degrees . All the three meth-oxy groups are almost co-planar with the bound benzene ring [r.m.s. deviation of 0.0306 (2) A]. A weak C-H?O intra molecular inter-action involving one of the ortho-meth-oxy groups generates an S(6) ring motif. In the crystal, the mol-ecules are linked by weak C-H?O inter actions into anti-parallel face-to-face pairs. Adjacent pairs are further connected into sheets parallel to the ab plane. PMID- 22065836 TI - 3,4-Dimethyl-anilinium 4-methyl-benzene-sulfonate. AB - In the crystal structure of the title compound, C(8)H(12)N(+).C(7)H(7)O(3)S(-), N H?O hydrogen bonds link the cations and anions into ribbons parallel to the c axis. N-H?S inter-actions also occur. PMID- 22065837 TI - 2-(2-Chloro-phen-yl)-3-methyl-5,6-diphenyl-2,3-dihydro-pyrazine. AB - In the title mol-ecule, C(23)H(19)ClN(2), the heterocyclic ring adopts a screw boat conformation, with all substituents equatorial. The benzene ring at position 2 makes dihedral angles of 77.88 (12) and 76.31 (12) degrees with the phenyl rings at positions 5 and 6, respectively. The dihedral angle between the phenyl rings at positions 5 and 6 is 70.05 (10) degrees . The Cl atom is disordered over two positions with occupancy factors of 0.946 (5) and 0.054 (5). In the crystal, C-H?pi inter-actions are found. PMID- 22065838 TI - A NOD to zebrafish models of inflammatory bowel disease pathogenesis. PMID- 22065839 TI - Pathological looping in the synucleinopathies: investigating the link between Parkinson's disease and Gaucher disease. PMID- 22065840 TI - Mouse genetics for studying mechanisms of deafness and more: an interview with Karen Steel. Interview by Sarah Allan. PMID- 22065842 TI - Regulating complement in the kidney: insights from CFHR5 nephropathy. AB - Complement factor H related protein 5 (CFHR5) nephropathy is a monogenic disorder of complement regulation that is endemic in Cyprus. The disease is characterised by haematuria, C3 glomerulonephritis and kidney failure. Its identification suggests a role for the CFHR5 protein in the regulation of complement in the kidney. In this review, we discuss how studying CFHR5 nephropathy can contribute to our understanding of the role of complement in kidney diseases such as dense deposit disease, C3 glomerulonephritis and atypical haemolytic uraemic syndrome. PMID- 22065843 TI - Lactate shuttles at a glance: from physiological paradigms to anti-cancer treatments. AB - Hypoxia and oncogene expression both stimulate glycolytic metabolism in tumors, thereby leading to lactate production. However, lactate is more than merely a by product of glycolysis: it can be used as a metabolic fuel by oxidative cancer cells. This phenomenon resembles processes that have been described for skeletal muscle and brain that involve what are known as cell-cell and intracellular lactate shuttles. Two control points regulate lactate shuttles: the lactate dehydrogenase (LDH)-dependent conversion of lactate into pyruvate (and back), and the transport of lactate into and out of cells through specific monocarboxylate transporters (MCTs). In tumors, MCT4 is largely involved in hypoxia-driven lactate release, whereas the uptake of lactate into both tumor cells and tumor endothelial cells occurs via MCT1. Translating knowledge of lactate shuttles to the cancer field offers new perspectives to therapeutically target the hypoxic tumor microenvironment and to tackle tumor angiogenesis. PMID- 22065846 TI - Off-pump vs. on-pump CABG: are we any closer to a resolution? PMID- 22065844 TI - Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity. AB - The close correspondence between energy intake and expenditure over prolonged time periods, coupled with an apparent protection of the level of body adiposity in the face of perturbations of energy balance, has led to the idea that body fatness is regulated via mechanisms that control intake and energy expenditure. Two models have dominated the discussion of how this regulation might take place. The set point model is rooted in physiology, genetics and molecular biology, and suggests that there is an active feedback mechanism linking adipose tissue (stored energy) to intake and expenditure via a set point, presumably encoded in the brain. This model is consistent with many of the biological aspects of energy balance, but struggles to explain the many significant environmental and social influences on obesity, food intake and physical activity. More importantly, the set point model does not effectively explain the 'obesity epidemic'--the large increase in body weight and adiposity of a large proportion of individuals in many countries since the 1980s. An alternative model, called the settling point model, is based on the idea that there is passive feedback between the size of the body stores and aspects of expenditure. This model accommodates many of the social and environmental characteristics of energy balance, but struggles to explain some of the biological and genetic aspects. The shortcomings of these two models reflect their failure to address the gene-by-environment interactions that dominate the regulation of body weight. We discuss two additional models--the general intake model and the dual intervention point model--that address this issue and might offer better ways to understand how body fatness is controlled. PMID- 22065856 TI - Distribution of the homeostasis model assessment of insulin resistance in Mexican children and adolescents. AB - OBJECTIVE: Several cutoff points of the homeostasis model assessment of insulin resistance (HOMA-IR; varying from 2.5 to 4.0) have been suggested for diagnosing IR in youth. In this study, we determined the distribution of the HOMA-IR in Mexican children and adolescents. DESIGN AND METHODS: A total of 6132 children and adolescents from San Luis Potosi, Leon, Queretaro, and Durango, which are cities in central and northern Mexico, were enrolled in a population-based cross sectional study. Eligible participants were apparently healthy children and adolescents aged 6-18 years. Pregnancy and the presence of chronic illnesses were exclusion criteria. RESULTS: A total of 3701 (60.3%) girls and 2431 (39.7%) boys were included in this study. In the overall population, the mean body mass index, insulin levels, and fasting glucose levels were 21.8+/-1.3 kg/m(2), 7.1+/-3.2 MUU/ml, and 86.2+/-10.0 mg/dl respectively. The concentrations of insulin and fasting glucose gradually increased from 6 to 12 years of age, whereas the concentrations tended to plateau in the 13- to 18-year-old population. The absolute mean of the HOMA-IR was 2.89+/-0.7. The HOMA-IR gradually increased with age and reached a plateau at 13 years of age. CONCLUSIONS: Because the insulin concentrations, glucose levels, and HOMA-IR exhibited a gradual increase with age that was not related to obesity, our results suggested that the evaluation of IR in children should be based on percentiles of the HOMA-IR rather than a dichotomous value derived from a single cutoff point. PMID- 22065857 TI - DG3173 (somatoprim), a unique somatostatin receptor subtypes 2-, 4- and 5 selective analogue, effectively reduces GH secretion in human GH-secreting pituitary adenomas even in Octreotide non-responsive tumours. AB - OBJECTIVE: Somatostatin analogues (SSA) reduce autonomous GH secretion by activating somatostatin receptors (sst) 2 and 5 in 50-60% of acromegalic patients. However, by inhibiting insulin secretion these SSA reduce glucose tolerance. DG3173 is a novel SSA with additional binding to sst4 and low insulin suppressing activity. We investigated the effect of DG3173, including its relation to specific tumour characteristics, on GH secretion in human somatotroph adenoma cell cultures (hSA) in comparison with Octreotide. METHODS: Twenty-seven hSA were characterised immunohistochemically for their hormone- and sst expression, granularity and pre-surgical therapy with SSA. GH was determined in supernatants of hSA treated with DG3173 or Octreotide in time- (n=6) and dose response (n=21) experiments. A positive response was defined as GH suppression to below 80% of baseline. RESULTS: In the dose-response experiments DG3173 suppressed GH secretion in more adenomas than Octreotide (10/21 vs 5/21), including 38% (6/16) of Octreotide non-responders. In responders the extent of GH suppression and IC(50) were comparable for both SSA. The response-rate of both SSA was higher in monohormonal vs bihormonal adenomas, yet GH declined similarly in both groups. Neither pre-surgical SSA (n=6) nor tumour morphology was related to the GH response. However, semi-quantitative analysis indicated a small but significant negative correlation between the GH response to Octreotide and the immunoreactivity scores of sst2 expression. CONCLUSIONS: DG3173 equalled Octreotide in suppressing GH secretion in hSA. Since DG3173 suppressed GH in some Octreotide-non-responsive adenomas, its clinical effectiveness will be worth testing. Moreover, its reduced insulin-suppressive potency would make it a valuable alternative to Octreotide. PMID- 22065859 TI - Follicular assembly: mechanisms of action. AB - The differentiation of primordial germ cells (PGCs) into functional oocytes is important for the continuation of species. In mammals, PGCs begin to differentiate into oocytes during embryonic development. Oocytes develop in clusters called germ line cysts. During fetal or neonatal development, germ cell cysts break apart into single oocytes that become surrounded by pregranulosa cells to form primordial follicles. During the process of cyst breakdown, a subset of cells in each cyst undergoes cell death with only one-third of the initial number of oocytes surviving to form primordial follicles. The mechanisms that control cyst breakdown, oocyte survival, and follicle assembly are currently under investigation. This review describes the mechanisms that have been implicated in the control of primordial follicle formation, which include programmed cell death regulation, growth factor and other signaling pathways, regulation by transcription factors and hormones, meiotic progression, and changes in cell adhesion. Elucidation of mechanisms leading to formation of the primordial follicle pool will help research efforts in ovarian biology and improve treatments of female infertility, premature ovarian failure, and reproductive cancers. PMID- 22065860 TI - Porcine uterus contains a population of mesenchymal stem cells. AB - The uterus has a remarkable ability of cycling remodeling throughout the reproductive life of the female. Recent findings in the human and mouse indicate that adult stem/progenitor cells may play a prominent role in the maintenance of uterine endometrial and myometrial homeostasis. We aimed to characterize the prospective stem/progenitor cells in the porcine uterus and establish a new model for uterine stem cell research. In this study, we demonstrated that cells isolated from porcine uterus have capacity for in vitro differentiation into adipogenic and osteogenic lineages and express the mesenchymal stem cell (MSC) markers CD29, CD44, CD144, CD105, and CD140b as revealed by RT-PCR. Moreover, we showed that some cells isolated from the porcine uterus when cultured at low density produce large clones with an efficiency of 0.035%. Simultaneously, they were negative for hematopoietic stem cell markers such as CD34 and CD45. Low expression of nestin, which is specific for neural stem cells and various progenitor cells, was also detected. We conclude that the porcine uterus contains a small population of undifferentiated cells with MSC-like properties similar to human and mouse uteri. PMID- 22065858 TI - Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders: Thematic Review Series: Genetics of Human Lipid Diseases. AB - As the specific composition of lipids is essential for the maintenance of membrane integrity, enzyme function, ion channels, and membrane receptors, an alteration in lipid composition or metabolism may be one of the crucial changes occurring during skeletal and cardiac myopathies. Although the inheritance (autosomal dominant, autosomal recessive, and X-linked traits) and underlying/defining mutations causing these myopathies are known, the contribution of lipid homeostasis in the progression of these diseases needs to be established. The purpose of this review is to present the current knowledge relating to lipid changes in inherited skeletal muscle disorders, such as Duchenne/Becker muscular dystrophy, myotonic muscular dystrophy, limb-girdle myopathic dystrophies, desminopathies, rostrocaudal muscular dystrophy, and Dunnigan-type familial lipodystrophy. The lipid modifications in familial hypertrophic and dilated cardiomyopathies, as well as Barth syndrome and several other cardiac disorders associated with abnormal lipid storage, are discussed. Information on lipid alterations occurring in these myopathies will aid in the design of improved methods of screening and therapy in children and young adults with or without a family history of genetic diseases. PMID- 22065861 TI - Comparison of 7alpha-methyl-19-nortestosterone effectiveness alone or combined with progestins on androgen receptor mediated-transactivation. AB - 7alpha-methyl-19-nortestosterone (MENT) is an androgen with potent gonadotropin inhibitory activity and prostate-sparing effects. These attributes give MENT advantages over testosterone as a male contraceptive, but, as in the case of testosterone, a partial dose-dependent suppression of spermatogenesis has been observed. Combination of testosterone or MENT with synthetic progestins improves the rate of azoospermia; however, it is unknown whether these combinations affect hormone androgenicity or exert synergistic effects via progestational or androgenic interaction. Herein, using transactivation assays, we examined the ability of MENT alone or combined with several 19-nor-derived synthetic progestins to activate androgen receptor (AR)-dependent gene transcription. In addition, the capability of 7alpha-methyl-estradiol (7alpha-methyl-E(2)), an aromatized metabolite of MENT, to transactivate gene transcription via estrogen receptor alpha (ERalpha; ESR1) or ERbeta (ESR2) was also investigated. As expected, MENT induced gene transactivation through either the progesterone receptor (PGR) or the AR. MENT was as efficient as progesterone in activating PGR mediated reporter gene expression, but it was ten times more potent than testosterone and dihydrotestoterone in activating of AR-driven gene expression. The addition of increasing concentrations of other 19-nortestosterone derivatives (norethisterone or levonorgestrel) did not affect, in a significant manner, the ability of MENT to activate AR-dependent reporter gene transcription. The same results were obtained with different cell lines. 7alpha-Methyl-E(2) resulted in potent estrogen activity via both ER subtypes with efficiency similar to natural E(2). These results suggest that the addition of 19-nortestosterone-derived progestins, as a hormonal adjuvant in male fertility strategies for effective spermatogenic suppression, does not display any detrimental effect that would interfere with MENT androgenic transcriptional activity. PMID- 22065862 TI - Normalizing action of exendin-4 and GLP-1 in the glucose metabolism of extrapancreatic tissues in insulin-resistant and type 2 diabetic states. AB - Exendin-4 (Ex-4) mimics glucagon-like peptide-1 (GLP-1 or GCG as listed in the HUGO database), being anti-diabetic and anorectic, in stimulating glucose and lipid metabolism in extrapancreatic tissues. We studied the characteristics of Ex 4 and GLP-1 action, during prolonged treatment, on GLUTs expression (mRNA and protein), glycogen content (GC), glucose transport (GT), glycogen synthase a (GSa), and kinase (PI3K and MAPKs) activity, in liver, muscle, and fat of insulin resistant (IR, by fructose) and type 2 diabetic (T2D, streptozotocin at birth) rats compared with normal rats. In both IR and T2D, the three tissues studied presented alterations in all measured parameters. In liver, GLP-1 and also Ex-4 normalized the lower than normal Glut2 (Slc2a2) expression and showed a trend to normalize the reduced GC in IR, and GLP-1, like Ex-4, also in T2D, effects mediated by PI3K and MAPKs. In skeletal muscle, neither GLP-1 nor Ex-4 modified Glut4 (Slc2a4) expression in either experimental model but showed normalization of reduced GT and GSa, in parallel with the normalization of reduced PI3K activity in T2D and MAPKs in both models. In adipose tissue, the altered GLUT4 expression in IR and T2D, along with reduced GT in IR and increased GT in T2D, and with hyperactivated PI3K in both, became normal after GLP-1 and Ex-4 treatment; yet, MAPKs, that were also higher, became normal only after Ex-4 treatment. The data shows that Ex-4, as well as GLP-1, exerts a normalizing effect on IR and T2D states through a distinct post-receptor mechanism, the liver being the main target for Ex-4 and GLP-1 to control glucose homeostasis. PMID- 22065863 TI - Longitudinal structure-function correlates in elderly reveal MTL dysfunction with cognitive decline. AB - By integrating behavioral measures and imaging data, previous investigations have explored the relationship between biological markers of aging and cognitive functions. Evidence from functional and structural neuroimaging has revealed that hippocampal volume and activation patterns in the medial temporal lobe (MTL) may predict cognitive performance in old age. Most past demonstrations of age-related differences in brain structure-function were based on cross-sectional comparisons. Here, the relationship between 6-year intraindividual change in functional magnetic resonance imaging (fMRI) signal and change in memory performance over 2 decades was examined. Correlations between intraindividual change in fMRI signal during episodic encoding and change in memory performance measured outside of scanning were used as an estimate for relating brain-behavior changes. The results revealed a positive relationship between activation change in the hippocampus (HC) and change in memory performance, reflecting reduced hippocampal activation in participants with declining performance. Using a similar analytic approach as for the functional data, we found that individuals with declining performance had reduced HC volume compared with individuals with intact performance. These observations provide a strong link between cognitive change in older adults and MTL structure and function and thus provide insights into brain correlates of individual variability in aging trajectories. PMID- 22065864 TI - Differential expression patterns of striate cortex-enriched genes among Old World, New World, and prosimian primates. AB - A group of 5 genes, OCC1, testican-1, testican-2, 5-HT1B, and 5-HT2A, are selectively expressed in layer 4 (4C of Brodmann) of striate cortex (visual area V1) of both Old World macaques and New World marmoset monkeys. The expression of these genes is activity dependent, as expression is reduced after blocking retinal activity. Surprisingly, the pronounced expression pattern has not been found in rodents or carnivores. Thus, these genes may be highly expressed in V1 of some but perhaps not all primates. Here, we compared the gene expression in members of 3 major branches of primate evolution: prosimians, New World monkeys, and Old World monkeys. Although the expression pattern of 5-HT1B was well conserved, those of the other genes varied from the least distinct in prosimian galagos to successively more in New World owl monkeys, marmosets, squirrel monkeys, and Old World macaque monkeys. In owl monkeys, the expression of 5-HT2A was significantly reduced by monocular tetrodotoxin injection, while those of OCC1 and 5-HT1B were not. Thus, we propose that early primates had low levels of expression and higher levels emerged with anthropoid primates and became further enhanced in the Old World catarrhine monkeys that are more closely related to humans. PMID- 22065865 TI - Use of an automatic application for wall motion classification based on longitudinal strain: is it affected by operator expertise in echocardiography? A multicentre study by the Israeli Echocardiography Research Group. AB - AIMS: Assessing the quality of wall motion (WM) on echocardiograms remains a challenge. Previously, we validated an automated application used by experienced echocardiographers for WM classification based on longitudinal two-dimensional (2D) strain. The aim of this study was to show that the use of this automatic application was independent of the user's experience. METHODS AND RESULTS: We compared the WM classifications obtained by the application when used by 12 highly experienced readers (Exp-R) vs. 11 inexperienced readers (InExp-R). Both classifications were compared with expert consensus classifications using the standard visual method. Digitized clips of cardiac cycles from three apical views in 105 patients were used for these analyses. Reproducibility of both groups was high (overall intra-class correlation coefficient: InExp-R = 0.89, Exp-R = 0.83); the lowest was noted for hypokinetic segments (InExp-R = 0.79, Exp-R = 0.72). InExp-R scores were concordant with Exp-R mode scores in 88.8% of segments; they were overestimated in 5.8% and underestimated in 3.2%. The sensitivity, specificity, and accuracy of InExp-R vs. Exp-R for classifying segments as normal/abnormal were identical (87, 85, and 86%, respectively). CONCLUSION: Classification of WM from apical views with an automatic application based on longitudinal 2D strain by InExp-R vs. Exp-R was similar to visual classification by Exp-R. This application may be useful for inexperienced echocardiographers/technicians and may serve as an automated 'second opinion' for experienced echocardiographers. PMID- 22065866 TI - Multi-modality imaging of apical aortic conduit. PMID- 22065867 TI - Penicilliosis in children without HIV infection--are they immunodeficient? AB - BACKGROUND: Penicillium marneffei infection is indigenous to Southeast Asia. Majority of penicilliosis occurs in patients with AIDS, and less commonly with secondary immunodeficiencies. Penicilliosis is rare in otherwise healthy persons, but information on their immunological status is often lacking. METHODS: From 1996 to 2009, we diagnosed penicilliosis in 5 children. Their clinical features, immunological findings, and genetic studies were analyzed. A systematic review of the English and Chinese literature was performed. Case reports/series on patients <18 years with penicilliosis were included, and patients stated to be human immunodeficiency virus (HIV)-positive excluded. RESULTS: All of our 5 patients were HIV negative. Presentations included fungemia (n = 2), multifocal lymphadenopathy (n = 2), and necrotizing pneumonia (n = 1). Four patients had recurrent mucocutaneous candidiasis. Hyperimmunoglobin E syndrome was diagnosed in 1 patient, while another had functional defect in interleukin-12/interferon gamma axis. Three patients were lymphopenic with low natural killer cell counts, but a specific immune defect was not identified. Systematic review of 509 reports on human penicilliosis identified 32 patients aged 3 months to 16 years with no known HIV infection. Twenty-four patients (75%) had disseminated disease, and 55% died of penicilliosis. Eight patients had primary immunodeficiencies or blood disorders, while 4 others had abnormal immune functions. Immune evaluations of the remaining patients were unstated. CONCLUSION: Penicilliosis is a severe disease causing high mortality in children. As an AIDS-defining illness, penicilliosis should be regarded as an indicator for underlying immunodeficiency in HIV-negative individuals. Immunological investigations should be performed, especially in those with recurrent infections. Multicentered collaborative studies are needed to collect information on long-term prognosis and define immune defects underlying penicilliosis. PMID- 22065868 TI - Experiential and rational decision making: a survey to determine how emergency physicians make clinical decisions. AB - BACKGROUND: Dual-process psychological theories argue that clinical decision making is achieved through a combination of experiential (fast and intuitive) and rational (slower and systematic) cognitive processes. OBJECTIVE: To determine whether emergency physicians perceived their clinical decisions in general to be more experiential or rational and how this compared with other physicians. METHODS: A validated psychometric tool, the Rational Experiential Inventory (REI 40), was sent through postal mail to all emergency physicians registered with the College of Physicians and Surgeons of Ontario, according to their website in November 2009. Forty statements were ranked on a Likert scale from 1 (Definitely False) to 5 (Definitely True). An initial survey was sent out, followed by reminder cards and a second survey to non-respondents. Analysis included descriptive statistics, Student t tests, analysis of variance and comparison of mean scores with those of cardiologists from New Zealand. RESULTS: The response rate in this study was 46.9% (434/925). The respondents' median age was 41-50 years; they were mostly men (72.6%) and most had more than 10 years of clinical experience (66.8%). The mean REI-40 rational scores were higher than the experiential scores (3.93/5 (SD 0.35) vs 3.33/5 (SD 0.49), p<0.0001), similar to the mean scores of cardiologists from New Zealand (mean rational 3.93/5, mean experiential 3.05/5). The mean experiential scores were significantly higher for female respondents than for male respondents (3.40/5 (SD 0.49) vs 3.30/5 (SD 0.48), p=0.003). CONCLUSIONS: Overall, emergency physicians favoured rational decision making rather than experiential decision making; however, female emergency physicians had higher experiential scores than male emergency physicians. This has important implications for future knowledge translation and decision support efforts among emergency physicians. PMID- 22065869 TI - Short- and long-term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST-segment elevation myocardial infarction: a meta-analysis of randomized control trials. AB - AIMS: Bone marrow stem cell (BMSC) treatment of ST-segment elevation myocardial infarction (STEMI) has been primarily via the intracoronary route or via endogenous mobilization using granulocyte colony-stimulating factor (G-CSF). Studies have provided conflicting results. We therefore performed a meta-analysis of these treatments, examining short- and long-term efficacy and safety. METHODS AND RESULTS: Randomized controlled trials (RCTs) of BMSC-based therapy for STEMI, delivered within 9 days of reperfusion, were identified by systematic search. Random effects models were used to calculate pooled effects of clinical outcomes, with meta-regression to assess dependence of the magnitude of effect sizes on study characteristics. Twenty-nine RCTs enrolling 1830 patients were included. Intracoronary BMSC therapy resulted in an overall improvement in left ventricular ejection fraction (LVEF) of 2.70% [95% confidence interval (CI) 1.48-3.92; P < 0.001] in the short term and 3.31% (95% CI 1.87-4.75; P < 0.001) longer term. Meta-regression suggested a dose-response relationship between quantity of CD34(+) cells delivered and increase in LVEF (P = 0.007). G-CSF treatment resulted in a trend towards similar benefits (P = 0.20). No significant differences were observed in pooled adverse outcome rates between intervention and control groups of either treatment approach, except for lower revascularization rates with intracoronary BMSC vs. control (odds ratio 0.68, 95% CI 0.47-0.97; P = 0.03). CONCLUSIONS: Intracoronary BMSC therapy post-STEMI improves LVEF beyond standard medical treatment, in both the short and longer term. G-CSF treatment shows positive but non-significant trends. Both treatments demonstrate safety comparable with conventional medical treatment. PMID- 22065870 TI - Exercise training in recently hospitalized heart failure patients enrolled in a disease management programme: design of the EJECTION-HF randomized controlled trial. AB - AIMS: The Exercise Joins Education: Combined Therapy to Improve Outcomes in Newly discharged Heart Failure (EJECTION-HF) study will evaluate the impact of a supervised exercise training programme (ETP) on clinical outcomes in recently hospitalized heart failure patients attending a disease management programme (DMP). Methods This multisite, pragmatic randomized controlled trial enrols patients discharged from participating hospitals with clinical evidence of heart failure who are willing and able to participate in a DMP and considered clinically safe to exercise. Enrolment includes participants with impaired and preserved left ventricular systolic function. Baseline assessment and programme commencement occur within 6 weeks of hospital discharge. The control group DMP includes individualized education and follow-up from a multidisciplinary heart failure team; a weekly education programme for 12 weeks; self-management advice; and medical follow-up. Home exercise is recommended for all participants. In addition, intervention participants are offered 36 supervised, structured gym based 1 h exercise sessions over 24 weeks. Sessions are tailored to exercise capacity and include aerobic, resistance, and balance exercises. Enrolment target is 350 participants. Primary outcome is 12-month mortality and readmissions. Secondary outcomes include blinded evaluation of depressive symptoms, sleep quality, cognition, and functional status (activities of daily living, 6 min walk distance, grip strength) at 3 and 6 months. A cost-utility analysis will be conducted. CONCLUSION: This study will enrol a representative group of hospitalized heart failure patients and measure a range of patient and health service outcomes to inform the design of post-hospital DMPs for heart failure. Enrolment will be completed in 2013. ACTRN12608000263392. PMID- 22065871 TI - Ventricular automaticity as a predictor of sudden death in ischaemic heart disease. AB - Opinion has oscillated in the cardiology community regarding the significance of ventricular premature beats and non-sustained ventricular tachycardia as predictors of sudden cardiac death. Automaticity can be a marker of underlying structural heart disease. It is unclear whether the apparent association with sudden death is simply a reflection of this fact. Older data are unreliable as the populations studied probably had a high prevalence of unrecognized structural heart disease. Current risk stratification is imperfect. The balance of evidence suggests that automaticity does predict risk and it may have a role in risk assessment algorithms, but at present the dataset is insufficient. PMID- 22065872 TI - Quantitative analysis of response to treatment with erlotinib in advanced non small cell lung cancer using 18F-FDG and 3'-deoxy-3'-18F-fluorothymidine PET. AB - The purpose of this study was to evaluate the relevance for the prediction of clinical benefit of first-line treatment with erlotinib using different quantitative parameters for PET with both (18)F-FDG and 3'-deoxy-3'-(18)F fluorothymidine ((18)F-FLT) in patients with advanced non-small cell lung cancer. METHODS: Data were used from a prospective trial involving patients with untreated stage IV non-small cell lung cancer. (18)F-FDG PET and (18)F-FLT PET were performed before and 1 (early) and 6 (late) weeks after erlotinib treatment. Several quantitative standardized uptake values (SUVs) using different definitions of volumes of interest with varying isocontours (maximum SUV [SUV(max)], 2-dimensional peak SUV [SUV(2Dpeak)], 3-dimensional [3D] peak SUV [SUV(3Dpeak)], 3D isocontour at 50% of the maximum pixel value [SUV(50)], 3D isocontour at 50% adapted for background [SUV(A50)], 3D isocontour at 41% of the maximum pixel value adapted for background [SUV(A41)], 3D isocontour at 70% of the maximum pixel value [SUV(70)], 3D isocontour at 70% adapted for background [SUV(A70)], and relative SUV threshold level [SUV(RTL)]) and metabolically active volume measurements were obtained in the hottest single tumor lesion and in the sum of up to 5 lesions per scan in 30 patients. Metabolic response was defined as a minimum reduction of 30% in each of the different SUVs and as a minimum reduction of 45% in metabolically active volume. Progression-free survival (PFS) was compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan-Meier statistics and a log-rank test. RESULTS: Patients with a metabolic response on early (18)F-FDG PET and (18)F-FLT PET in the hottest single tumor lesion as well as in the sum of up to 5 lesions per scan had a significantly longer PFS, regardless of the method used to calculate SUV. However, the highest significance was obtained for SUV(max), SUV(50), SUV(A50), and SUV(A41.) Patients with a metabolic response measured by SUV(max) and SUV(3Dpeak) on late (18)F-FDG PET in the hottest single tumor lesion had a significantly longer PFS. Furthermore, Kaplan-Meier analyses showed a strong association between PFS and response seen by metabolically active volume, measured either in early (18)F-FLT or in late (18)F-FDG. CONCLUSION: Early (18)F FDG PET and (18)F-FLT PET can predict PFS regardless of the method used for SUV calculation. However, SUV(max), SUV(50), SUV(A50), and SUV(A41) measured with (18)F-FDG might be the best robust SUV to use for early response prediction. Metabolically active volume measurement in early (18)F-FLT PET and late (18)F-FDG PET may have an additional predictive value in monitoring response in patients with advanced non-small cell lung cancer treated with erlotinib. PMID- 22065874 TI - 18F-FDG PET/CT as a sensitive and early treatment monitoring tool: will this become the major thrust for its clinical application in infectious and inflammatory disorders? PMID- 22065875 TI - A pilot study to evaluate 3'-deoxy-3'-18F-fluorothymidine pet for initial and early response imaging in mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma. Proliferation activity is considered an important prognostic marker. Immunohistochemical analysis from core biopsy or lymph node may not represent the proliferation rate. We investigated the in vivo proliferation marker 3'-deoxy-3'-(18)F fluorothymidine ((18)F-FLT) to characterize MCL. METHODS: Eight untreated MCL patients were recruited prospectively. (18)F-FLT PET/CT was performed 45 min after injection of (18)F-FLT. (18)F-FDG PET/CT served as reference. Mean (18)F FLT standardized uptake values were assessed per lesion and compared with respective (18)F-FDG uptake. Correlation of mean (18)F-FLT and (18)F-FDG uptake in the hottest lesion to Ki67 immunostaining was performed. Five patients underwent repetitive early (18)F-FLT PET. RESULTS: All lymphoma lesions identified by (18)F-FDG PET/CT showed increased (18)F-FLT uptake. Semiquantitative analysis revealed a high mean (18)F-FLT standardized uptake value of 9.9 (range, 5.5-15.9). Mean (18)F-FLT uptake and Ki67 expressions showed a strong positive correlation. CONCLUSION: PET using (18)F-FLT as a biomarker for proliferative activity showed a high sensitivity for MCL. (18)F-FLT uptake shows a correlation with proliferation. Our results warrant further analysis of (18)F FLT PET in MCL. PMID- 22065876 TI - In vivo near-infrared fluorescence imaging of integrin alpha2beta1 in prostate cancer with cell-penetrating-peptide-conjugated DGEA probe. AB - The overexpression of integrin alpha(2)beta(1) has been demonstrated to correlate with prostate tumor aggressiveness and metastatic potential. Recently, we reported that the DGEA peptide is a promising targeting ligand for near-infrared fluorescence and microPET imaging of integrin alpha(2)beta(1) expression in prostate cancers. Here, we aimed to further improve the targeting efficacy of this peptide by incorporating a series of cell-penetrating peptides (CPPs) into the DGEA sequence. METHODS: After the conjugation with appropriate fluorescent dyes, the CPP-DGEA peptides were evaluated in human prostate cell lines (PC-3, CWR-22, and LNCaP) that contain different integrin alpha(2)beta(1) expression levels. In addition, to reduce excess kidney uptake, a carboxypeptidase-specific sequence Gly-Lys was incorporated into the probe design, allowing for cleavage by the kidney brush border enzymes of the CPP before uptake by proximal tubule cells. RESULTS: Although the CPP motif greatly facilitated the translocation of CPP-DGEA without affecting binding specificity in vitro, fluorescent dye-labeled CPP-DGEA demonstrated extremely high kidney uptake in vivo. Kidney uptake was dramatically decreased after a carboxypeptidase-specific peptide linker (Gly-Lys) had been incorporated into the probe design. The optimized probe demonstrated a prominent accumulation of activity in PC-3 tumor (integrin alpha(2)beta(1) positive). Receptor specificity was confirmed with blocking experiments and evaluation in a CWR-22 control tumor model with low alpha(2)beta(1) expression. CONCLUSION: This study demonstrated that the introduction of a CPP sequence can facilitate the internalization of an integrin-targeted peptide probe in vitro. Moreover, a cleavable peptide linker successfully reduced kidney uptake while preserving good tumor uptake in vivo. PMID- 22065877 TI - Feasibility of 11C-acetate PET/CT for imaging of fatty acid synthesis in the atherosclerotic vessel wall. AB - Fatty acids are a common constituent of atherosclerotic plaque and may be synthesized in the plaque itself. Fatty acid synthesis requires acetyl-coenzyme-A (CoA) as a main substrate, which is produced from acetate. Currently, (11)C acetate PET/CT is used for the evaluation of malignancies. There are no data concerning its potential for the characterization of atherosclerotic plaque. Therefore, the purpose of the present study was to examine the prevalence, distribution, and topographic relationship of arterial (11)C-acetate uptake and vascular calcification in major arteries. METHODS: Thirty-six patients were examined by whole-body (11)C-acetate PET/CT. Tracer uptake in various arterial segments was analyzed both qualitatively and semiquantitatively by measuring the blood-pool-corrected standardized uptake value (target-to-background ratio). CT images were used to measure calcified plaque burden. RESULTS: (11)C-acetate uptake was observed at 220 sites in 32 (88.8%) of the 36 study patients, and mean target-to-background ratio was 2.5 +/- 1.0. Calcified atherosclerotic lesions were observed at 483 sites in 30 (83.3%) patients. Sixty-four (29.1%) of the 220 lesions with marked (11)C-acetate uptake were colocalized with arterial calcification. However, only 13.3% of all arterial calcification sites demonstrated increased radiotracer accumulation. CONCLUSION: Our data indicate the feasibility of using (11)C-acetate PET/CT for imaging of fatty acid synthesis in the atherosclerotic vessel wall. This study provides a rationale to incorporating (11)C-acetate PET into further preclinical and clinical studies to obtain new insights into fatty acid synthesis in atherosclerotic lesions and to evaluate whether it may be used to monitor pharmacologic intervention with fatty acid synthase inhibitors. PMID- 22065878 TI - Obituary. Anthony Clive James (1943-2011). PMID- 22065879 TI - Avoiding complications with Aptos sutures. AB - BACKGROUND: Over the past decade, several methods of minimally-invasive thread mediated lifting have been widely adopted in aesthetic surgery. Early use of these methods met with great enthusiasm, and threadlifting was often performed without sufficient regard for proper indications, controls, or outcomes. Soon after, reports of early-relapse ptosis, complications, and other undesirable side effects began to appear in the literature. OBJECTIVES: The authors describe the current best practices associated with threadlifting to ensure proper use and improved results. METHODS: The authors retrospectively reviewed their collective case data, analyzing the results of 12,788 face and neck threadlift procedures in 6098 patients over 12.5 years. RESULTS: The data showed inconsistent results and early relapse of deformity with the Aptos Thread and Aptos Thread 2G methods. Complications included thread visibility, migration, and exposure; linear bleeding along the needle course; skin dimpling; hypocorrection and hypercorrection; transient paresthesias; and a small number of cases of injury to major vessels, nerve branches, and parotid capsule/duct. As new devices were developed and the indications for each technique refined, soft tissue suspension became more effective and durable, and the incidence of complications correspondingly decreased in the latter part of the series. CONCLUSIONS: Threadlifting is a relatively modern trend in aesthetic surgery that demands a similarly novel approach from surgeons. When performed properly, threadlifting is associated with minor and infrequent complications and is a helpful clinical alternative to traditional facial rejuvenation techniques. PMID- 22065880 TI - The minimal access deep plane extended vertical facelift. AB - BACKGROUND: Modern facelift techniques have benefited from a "repopularization" of shorter incisions, limited skin elevation, and more limited dissection of the superficial musculoaponeurotic system (SMAS) and platysma in order to shorten postoperative recovery times and reduce surgical risks for patients. OBJECTIVES: The authors describe their minimal access deep plane extended (MADE) vertical vector facelift, which is a hybrid technique combining the optimal features of the deep plane facelift and the short scar, minimal access cranial suspension (MACS) lift. METHODS: The authors retrospectively reviewed the case records of 181 patients who underwent facelift procedures performed by the senior author (AAJ) during a two year period between March 2008 and March 2010. Of those patients, 153 underwent facelifting with the MADE vertical technique. With this technique, deep plane dissection releases the zygomatico-cutaneous ligaments, allowing for more significant vertical motion of the midface and jawline during suspension. Extended platysmal dissection was utilized with a lateral platysmal myotomy, which is not traditionally included in a deep plane facelift. The lateral platysmal myotomy allowed for separation of the vertical vector of suspension in the midface and jawline from the superolateral vector of suspension that is required for neck rejuvenation, obviating the need for additional anterior platysmal surgery. RESULTS: The average age of the patients was 57.8 years. The average length of follow-up was 12.7 months. In 69 consecutive patients from this series, average vertical skin excision measured 3.02 cm on each side of the face at the junction of the pre auricular and temporal hair tuft incision (resulting in a total excision of 6.04 cm of skin). Data from the entire series revealed a revision rate of 3.9%, a hematoma rate of 1.9%, and a temporary facial nerve injury rate of 1.3%. CONCLUSIONS: The common goal of all facelifting procedures is to provide a long-lasting, natural, balanced, rejuvenated aesthetic result with few complications and minimal downtime. The MADE vertical facelift fulfills these criteria and often yields superior results in the midface and neck areas, where many short scar techniques fail. Furthermore, this procedure can be performed under local anesthesia, which is a benefit to both patients and surgeons. PMID- 22065881 TI - The Lassus vertical technique. AB - In this historical perspective article, the author outlines the evolution of his vertical scar technique, first developed in 1964. He describes the procedure and reports the results of his 42-year experience with a series of 2000 breasts. PMID- 22065882 TI - Four-dimensional breast imaging, part II: clinical implementation and validation of a computer imaging system for breast augmentation planning. AB - BACKGROUND: No publications exist describing the impact of three-dimensional imaging on the consultation process for breast augmentation, nor have existing software products claiming simulation features been validated. OBJECTIVES: The authors describe the application of four-dimensional technology during patient consultation to assist in planning implant size and type. METHODS: Forty-six primary breast augmentation patients underwent preoperative consultation with 4D simulation software; 35 out of 46 also received follow-up imaging. At six months postoperatively, simulated measurements were compared to actual measurements and questionnaires were mailed to patients asking them to assess the imaging experience. A follow-up phone survey 18 months postoperatively examined the persistence of patient attitudes about implant size and imaging. Practice productivity was evaluated by comparing specific parameters (such as scheduling rates) between three separate time periods for the same clinic. RESULTS: Across all parameters, breast augmentation simulations correlated highly with positive surgical outcomes (R-value = 0.68). The majority (95%) of patients believed the simulations were accurate; 89% also expressed that it enhanced trust in the surgeon and 74% reporting that it helped in choosing an implant size. Despite 48% also indicating that they would select a larger implant if they were to undergo surgery again, no patients have undergone reoperations of any kind. Compared to historical controls, scheduling rates in the practice increased from 40% to 77% after addition of simulation software. CONCLUSIONS: 4D breast imaging appears to be an accurate system for analysis, planning, simulation, and patient education for women considering primary breast augmentation, and application of this technology during the consultation process was correlated with a high degree of patient satisfaction and practice productivity. PMID- 22065883 TI - Commentary on: Four-dimensional breast imaging, parts I and II. PMID- 22065884 TI - The influence of career stage, practice type and location, and physician's sex on surgical practices among board-certified plastic surgeons performing breast augmentation. AB - BACKGROUND: Breast augmentation is the most commonly performed cosmetic surgical procedure in the United States, but surgeon preferences in terms of technique and postoperative care regimen vary widely. OBJECTIVES: The authors investigated the influence of career stage, practice type and location, and physician's sex on surgical technique preferences among board-certified plastic surgeons performing breast augmentation. METHODS: In October 2009, an online survey was e-mailed to all active members of the American Society of Plastic Surgeons practicing within the United States. Response frequencies were calculated and correlated with surgeon demographics. RESULTS: From the pool of 4737 respondents, 898 responses were received (18.9%). Surgeons performing breast augmentation were more frequently male, between 46 and 65 years old, and had practiced for at least 20 years in solo private practice in a suburban setting. Surgical volume most frequently consisted of 10% to 25% cosmetic surgery, with 10 to 50 breast augmentations performed per year. Surgeons in practice for five years or less were more likely to use smooth, round silicone gel-filled implants, to select implants smaller than 300 cc, to use the dual-plane pocket, and to recommend yearly follow-up. Surgeons in practice for more than 20 years were more likely to select saline implants, utilize the subglandular plane, perform closed capsulotomy, and place drains. Surgeons at academic centers performed fewer breast augmentation surgeries and placed smaller implants than those in private practice, while surgeons in suburban locations performed more breast augmentations than those in urban or rural locations. Surgeons in the West performed the greatest number of augmentations, although the largest-sized implants were placed in the Southwest. Compared with men, women surgeons appeared significantly less likely to use saline implants, were less likely to perform more than 100 breast augmentations per year, and were significantly more likely to place implants less than 300 cc. CONCLUSIONS: Surgical preferences were associated with years in practice and included differences in technique and postoperative care. Practice location was associated with differences in procedural volume, implant size, incision location, and recommended follow-up time, while practice type was related to surgical volume, implant size, implant location, and percentage of cosmetic surgery performed. PMID- 22065885 TI - Minimal-scar handlift: a new surgical approach. AB - BACKGROUND: Removal of excess skin from the aging hand can cause scarring in one of the body's most visible areas, which is highly undesirable for patients. A minimal-scar approach to tightening this skin, in conjunction with the rejuvenating effects of minimally-invasive procedures, is therefore needed. OBJECTIVES: The authors describe a new technique for limiting scar size and visibility by locating the incision in a unique position on the ulnar side of the dorsum of the hand. METHODS: Eleven patients were treated with the authors' method between March and September 2009. Both hands were treated for each patient, but these procedures occurred separately, at an interval of two to four months. The surgical approach included skin flap advancement and rotation, and the procedure took place under local anesthesia and sedation. The resultant scar was S-shaped. Changes in postoperative stress ratio were visualized. RESULTS: Patients reported being highly satisfied with this procedure with regard to scar size, quality, and location. No major complications were observed, such as infection, flap necrosis, and nerve damage. All minor complications were treated conservatively. Patients with Fitzpatrick skin types I-III profited from less scar visibility in their outcomes. All patients experienced quick recovery with minimal downtime, independent of skin type. CONCLUSIONS: The minimal-scar handlift technique is an effective surgical approach to rejuvenating the hand and can be implemented concurrently with minimally-invasive techniques for volume restoration. The complication rate is low, and patient/surgeon satisfaction with outcomes is high. PMID- 22065886 TI - Commentary on: Minimal-scar handlift: a new surgical approach. PMID- 22065887 TI - Plastic surgery marketing in a generation of "tweeting". AB - BACKGROUND: "Social media" describes interactive communication through Web-based technologies. It has become an everyday part of modern life, yet there is a lack of research regarding its impact on plastic surgery practice. OBJECTIVES: The authors evaluate and compare the prevalence of classic marketing methods and social media in plastic surgery. METHODS: The Web sites of aesthetic surgeons from seven US cities were compared and evaluated for the existence of Facebook, Twitter, or MySpace links and promotions. To find the sites, the authors conducted a Google search for the phrase "plastic surgery" with the name of each city to be studied: Beverly Hills, California; Dallas, Texas; Houston, Texas; Las Vegas, Nevada; Miami, Florida; New York City, New York; and San Francisco, California. The trends of social networking memberships were also studied in each of these cities. RESULTS: In comparison to aesthetic surgeons practicing in other cities, those in Miami, Florida, favored social media the most, with 50% promoting a Facebook page and 46% promoting Twitter. Fifty-six percent of New York City aesthetic surgeons promoted their featured articles in magazines and newspapers, whereas 54% of Beverly Hills aesthetic surgeons promoted their television appearances. An increase in the number of new Facebook memberships among cosmetic providers in the seven cities began in October 2008 and reached a peak in October, November, and December 2009, with subsequent stabilization. The increase in the number of new Twitter memberships began in July 2008 and remained at a steady rate of approximately 15 new memberships every three months. CONCLUSIONS: Social media may seem like a new and unique communication tool, but it is important to preserve professionalism and apply traditional Web site building ethics and principles to these sites. We can expect continued growth in plastic surgeons' utilization of these networks to enhance their practices and possibly to launch direct marketing campaigns. PMID- 22065888 TI - "What not to wear" and other aspects of professionalism. PMID- 22065889 TI - Cosmetic plastic surgery training in the United Kingdom. PMID- 22065890 TI - Hydrogen quantum effects in hydride LaNi(5)H(7). AB - Energy eigenvalues and wave functions of hydrogen atoms in hydride LaNi(5)H(7) are calculated. First-principles electronic structure calculations are employed to obtain the three-dimensional potential energy structure of each hydrogen site. These quantum effects are not negligibly small in evaluation of enthalpy of formation, an important property of hydrogen storage. Including the temperature effect from hydrogen gas, experimental values are well reproduced. The excitation probability of inelastic neutron scattering is also calculated using the wave functions obtained. PMID- 22065891 TI - Effects of a Foster Parent Training Program on Young Children's Attachment Behaviors: Preliminary Evidence from a Randomized Clinical Trial. AB - Young children who enter foster care experience disruptions in care and maltreatment at a point when maintaining attachment relationships is a key, biologically based task. In previous research, we have found that young children experience challenges as they form attachments with new caregivers. They tend to push their new caregivers away, even though such children are especially in need of nurturing care. Further, many caregivers do not respond in nurturing ways when their children are distressed, which we have found is problematic for young children in foster care. We developed an intervention that is designed to help caregivers provide nurturance even when children do not elicit it, and even when it does not come naturally to them. This paper presents preliminary findings of the effectiveness of this intervention on children's attachment behaviors. Forty six children were randomly assigned to either the experimental intervention or to an educational intervention. For three consecutive days, attachment behaviors were reported across three distress-eliciting situations. Children whose parents had received the experimental intervention showed significantly less avoidance than children whose parents had received the educational intervention. These preliminary results suggest that the intervention is successful in helping children develop trusting relationships with new caregivers. PMID- 22065892 TI - Optimization of a Hybrid Magnetic Bearing for a Magnetically Levitated Blood Pump via 3-D FEA. AB - In order to improve the performance of a magnetically levitated (maglev) axial flow blood pump, three-dimensional (3-D) finite element analysis (FEA) was used to optimize the design of a hybrid magnetic bearing (HMB). Radial, axial, and current stiffness of multiple design variations of the HMB were calculated using a 3-D FEA package and verified by experimental results. As compared with the original design, the optimized HMB had twice the axial stiffness with the resulting increase of negative radial stiffness partially compensated for by increased current stiffness. Accordingly, the performance of the maglev axial flow blood pump with the optimized HMBs was improved: the maximum pump speed was increased from 6000 rpm to 9000 rpm (50%). The radial, axial and current stiffness of the HMB was found to be linear at nominal operational position from both 3-D FEA and empirical measurements. Stiffness values determined by FEA and empirical measurements agreed well with one another. The magnetic flux density distribution and flux loop of the HMB were also visualized via 3-D FEA which confirms the designers' initial assumption about the function of this HMB. PMID- 22065893 TI - Culturally-Competent Treatments for Asian Americans: The Relevance of Mindfulness and Acceptance-Based Psychotherapies. AB - The development of effective treatments for Asian Americans is important because treatment disparities continue to exist for this population. Because of their theoretical grounding in East Asian philosophies, mindfulness and acceptance based psychotherapies appear to constitute promising ways to provide culturally responsive mental health care to Asian Americans. However, in practice these approaches often reflect conceptions of mental health that are more consistent with Western world views. We review points of intersection and divergence between Western-based mindfulness and acceptance psychotherapies and Asian American cultural values. We then propose a culturally syntonic approach that accentuates certain components of mindfulness and acceptance psychotherapies and adapts other components of these approaches to be more consistent with Asian American cultural values. PMID- 22065894 TI - Development of standard digital images for pneumoconiosis. AB - We developed the standard digital images (SDIs) to be used in the classification and recognition of pneumoconiosis. From July 3, 2006 through August 31, 2007, 531 retired male workers exposed to inorganic dust were examined by digital (DR) and analog radiography (AR) on the same day, after being approved by our institutional review board and obtaining informed consent from all participants. All images were twice classified according to the International Labour Office (ILO) 2000 guidelines with reference to ILO standard analog radiographs (SARs) by four chest radiologists. After consensus reading on 349 digital images matched with the first selected analog images, 120 digital images were selected as the SDIs that considered the distribution of pneumoconiosis findings. Images with profusion category 0/1, 1, 2, and 3 were 12, 50, 40, and 15, respectively, and a large opacity were in 43 images (A = 20, B = 22, C = 1). Among pleural abnormality, costophrenic angle obliteration, pleural plaque and thickening were in 11 (9.2%), 31 (25.8%), and 9 (7.5%) images, respectively. Twenty-one of 29 symbols were present except cp, ef, ho, id, me, pa, ra, and rp. A set of 120 SDIs had more various pneumoconiosis findings than ILO SARs that were developed from adequate methods. It can be used as digital reference images for the recognition and classification of pneumoconiosis. PMID- 22065895 TI - Validity of self-reported healthcare utilization data in the Community Health Survey in Korea. AB - To evaluate the sensitivity and specificity of Community Health Survey (CHS), we analyzed data from 11,217 participants aged >= 19 yr, in 13 cities and counties in 2008. Three healthcare utilization indices (admission, outpatient visits, dental visits) as comparative variables and the insurance benefit claim data of the Health Insurance Review & Assessment Service as the gold-standard were used. The sensitivities of admission, outpatient visits, and dental visits in CHS were 54.8%, 52.1%, and 61.0%, respectively. The specificities were 96.4%, 85.6%, and 82.7%, respectively. This is the first study to evaluate the validity of nationwide health statistics resulting from questionnaire surveys and shows that CHS needs a lot of efforts to reflect the true health status, health behavior, and healthcare utilization of the population. PMID- 22065896 TI - Different clinical characteristics among Aeromonas hydrophila, Aeromonas veronii biovar sobria and Aeromonas caviae monomicrobial bacteremia. AB - This study aimed to compare the clinical presentations of Aeromonas hydrophila, A. veronii biovar sobria and A. caviae monomicrobial bacteremia by a retrospective method at three hospitals in Taiwan during an 8-yr period. There were 87 patients with A. hydrophila bacteremia, 45 with A. veronii biovar sobria bacteremia and 22 with A. caviae bacteremia. Compared with A. hydrophila and A. veronii biovar sobria bacteremia, A. caviae bacteremia was more healthcare associated (45 vs 30 and 16%; P = 0.031). The patients with A. caviae bacteremias were less likely to have liver cirrhosis (27 vs 62 and 64%; P = 0.007) and severe complications such as shock (9 vs 40 and 47%; P = 0.009) and thrombocytopenia (45 vs 67 and 87%; P = 0.002). The APACHE II score was the most important risk factor of Aeromonas bacteremia-associated mortalities. The APACHE II scores of A. caviae bacteremias were lower than A. hydrophila bacteremia and A. veronii biovar sobria bacteremia (7 vs 14 and 16 points; P = 0.002). In conclusion, the clinical presentation of A. caviae bacteremia was much different from A. hydrophila and A. veronii biovar sobria bacteremia. The severity and mortality of A. caviae bacteremia were lower than A. hydrophila or A. veronii biovar sobria bacteremia. PMID- 22065897 TI - Safety and immunogenicity of a new trivalent inactivated split-virus influenza vaccine in healthy Korean children: a randomized, double-blinded, active controlled, phase III study. AB - We report results of a randomized, double-blinded, active-controlled, phase III study conducted to evaluate the immunogenicity and safety of a new trivalent inactivated split-virus influenza vaccine (GC501) manufactured by the Green Cross Corporation in Korea. A total of 283 healthy children aged 6 months to < 18 yr were randomized to receive either GC501 or control. Of the GC501 recipients, seroconversion occurred in 48.5% for A/H1N1, 67.7% for A/H3N2 and 52% for influenza B. The proportion of subjects who had post-vaccination hemagglutination inhibition titers of 1:40 or greater was 90.7% for A/H1N1, 86.8% for A/H3N2 and 82.4% for influenza B in the GC501 recipients. No serious adverse events related to vaccination, or withdrawals because of adverse events were reported. The majority of solicited adverse events were mild in intensity. GC501 vaccine has good tolerability and favorable immunogenicity in children aged 6 months to < 18 yr. The addition of one more brand of influenza vaccine may allow for better global accessibility of vaccine for epidemics or future pandemics. PMID- 22065898 TI - Genes associated with recurrence of hepatocellular carcinoma: integrated analysis by gene expression and methylation profiling. AB - Gene expression is suppressed by DNA methylation. The goal of this study was to identify genes whose CpG site methylation and mRNA expression are associated with recurrence after surgical resection for hepatocellular carcinoma (HCC). Sixty-two HCCs were examined by both whole genome DNA methylation and transcriptome analysis. The Cox model was used to select genes associated with recurrence. A validation was performed in an independent cohort of 66 HCC patients. Among fifty nine common genes, increased CpG site methylation and decreased mRNA expression were associated with recurrence for 12 genes (Group A), whereas decreased CpG site methylation and increased mRNA expression were associated with recurrence for 25 genes (Group B). The remaining 22 genes were defined as Group C. Complement factor H (CFH) and myosin VIIA and Rab interacting protein (MYRIP) in Group A; proline/serine-rich coiled-coil 1 (PSRC1), meiotic recombination 11 homolog A (MRE11A), and myosin IE (MYO1E) in Group B; and autophagy-related protein LC3 A (MAP1LC3A), and NADH dehydrogenase 1 alpha subcomplex assembly factor 1 (NDUFAF1) in Group C were validated. In conclusion, potential tumor suppressor (CFH, MYRIP) and oncogenes (PSRC1, MRE11A, MYO1E) in HCC are reported. The regulation of individual genes by methylation in hepatocarcinogenesis needs to be validated. PMID- 22065899 TI - Intravenous KITENIN shRNA injection suppresses hepatic metastasis and recurrence of colon cancer in an orthotopic mouse model. AB - KITENIN (KAI1 C-terminal interacting tetraspanin) promotes invasion and metastasis in mouse colon cancer models. In the present study, we evaluated the effects of KITENIN knockdown by intravenous administration of short hairpin RNAs (shRNAs) in an orthotopic mouse colon cancer model, simulating a primary or adjuvant treatment setting. We established orthotopic models for colon cancer using BALB/c mice and firefly luciferase-expressing CT-26 (CT26/Fluc) cells. Tumor progression and response to therapy were monitored by bioluminescence imaging (BLI). In the primary therapy model, treatment with KITENIN shRNA substantially delayed tumor growth (P = 0.028) and reduced the incidence of hepatic metastasis (P = 0.046). In the adjuvant therapy model, KITENIN shRNA significantly reduced the extent of tumor recurrence (P = 0.044). Mice treated with KITENIN shRNA showed a better survival tendency than the control mice (P = 0.074). Our results suggest that shRNA targeting KITENIN has the potential to be an effective tool for the treatment of colon cancer in both adjuvant and metastatic setting. PMID- 22065900 TI - Calculation of the cardiothoracic ratio from portable anteroposterior chest radiography. AB - Cardiothoracic ratio (CTR), the ratio of cardiac diameter (CD) to thoracic diameter (TD), is a useful screening method to detect cardiomegaly, but is reliable only on posteroanterior chest radiography (chest PA). We performed this cross-sectional 3-phase study to establish reliable CTR from anteroposterior chest radiography (chest AP). First, CD(Chest PA)/CD(Chest AP) ratios were determined at different radiation distances by manipulating chest computed tomography to simulate chest PA and AP. CD(Chest PA) was inferred from multiplying CD(Chest AP) by this ratio. Incorporating this CD and substituting the most recent TD(Chest PA), we calculated the 'corrected' CTR and compared it with the conventional one in patients who took both the chest radiographies. Finally, its validity was investigated among the critically ill patients who performed portable chest AP. CD(Chest PA)/CD(Chest AP) ratio was {0.00099 * (radiation distance [cm])} + 0.79 (n = 61, r = 1.00, P < 0.001). The corrected CTR was highly correlated with the conventional one (n = 34, difference: 0.00016 +/- 0.029; r = 0.92, P < 0.001). It was higher in congestive than non-congestive patients (0.53 +/- 0.085; n = 38 vs 0.49 +/- 0.061; n = 46, P = 0.006). Its sensitivity and specificity was 61% and 54%. In summary, reliable CTR can be calculated from chest AP with an available previous chest PA. This might help physicians detect congestive cardiomegaly for patients undergoing portable chest AP. PMID- 22065901 TI - Relationships of basal level of serum 17-hydroxyprogesterone with that of serum androstenedione and their stimulated responses to a low dose of ACTH in young adult patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. AB - A single measurement of serum 17alpha-hydroxyprogesterone (17OHP) level can be unreliable because of its marked diurnal variation. We investigated the relationship of serum level of 17OHP with that of androstenedione (AD), which shows a smaller diurnal variation. And we tested whether the responses of these two hormones to low-dose ACTH stimulation are correlated in patients with 21 hydroxylase deficiency. Baseline serum 17OHP and AD levels were measured in 87 patients and a low-dose ACTH stimulation test was performed in 41 patients. The basal 17OHP level correlated positively with the basal AD level independently of sex, type of 21-hydroxylase deficiency, and the time of day of blood sampling (n = 87, R(2) = 0.75, P < 0.001). The area under the curve of 17OHP and AD correlated positively with their respective basal levels. The fold-change increase in 17OHP after ACTH injection correlated negatively with the basal 17OHP level, but that of AD did not correlate with the basal AD level. The random serum 17OHP level, used in the clinic, is a reliable guide and a low-dose ACTH stimulation test provides no extra benefit for assessing the treatment adequacy in patients with 21-hydroxylase deficiency. PMID- 22065902 TI - Overlapping medication associated with healthcare switching among Korean elderly diabetic patients. AB - This study was performed to describe the patterns of healthcare switching with overlapping use of anti-diabetic medication in the elderly using the Korea Health Insurance Review and Assessment Service's claims data. The study subjects were ambulatory elderly diabetic patients (ICD-10, E10-14) receiving at least one oral anti-diabetic drug or insulin, and visiting healthcare facilities more than two times between January and December 2005. A total of 457,975 elderly diabetic ambulatory care patients were identified. The mean of visiting frequencies was 9.0 ( +/- 3.6) and switching frequencies was 1.5 ( +/- 0.8) during 2005. Switching group consisted of 33% of total study subject. Healthcare switching was common in female patients who were older, and had treated polytherapy more in rural areas. The movement among primary care medical services was very common among the patients in the switching group (52.6%). A statistically significant correlation was observed between the healthcare switching and concomitant drug use (rho = 0.96), and overlapping days (rho = 0.57). The use of overlapping anti diabetic medication increased with the extent of healthcare switching. Further, frequent switching of healthcare between primary clinics was observed. Efforts should be made to establish continuity for the elderly diabetic patients with the identification of frequent switching with overlapping medication. PMID- 22065903 TI - Spirometric standards for healthy children and adolescents of Korean Chinese in northeast China. AB - In China there are 1,923,842 Korean Chinese, who live mostly (92.27%) in the country's three northeast provinces. In spite of this sizeable number, no spirometric data are available at present on them. The present study investigated normal spirometric reference values for the Korean Chinese children and adolescents. Spirometry was performed in 443 healthy Korean Chinese children and adolescents aged 8-18 yr with measurements of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF) and maximum mid expiratory flow (MMEF). Reference equations for FEV1, FVC, PEF and MMEF were derived by using multiple regression analysis. All of the measured spirometric parameters correlated positively with height and age significantly (P < 0.001). The predicted values of FVC and FEV1 were higher than values obtained by using Caucasian and other Asian equations (P < 0.001). A set of spirometric reference equations has been derived using a relatively large, healthy, non-smoking young Korean Chinese population with a wide range of ages and heights, the results of which differ from those gained from several other reference equations. These reference equations should be used for evaluation of lung function in this population. PMID- 22065904 TI - Sulforaphane induces antioxidative and antiproliferative responses by generating reactive oxygen species in human bronchial epithelial BEAS-2B cells. AB - Sulforaphane (SFN) is a naturally occurring compound which is known to induce the phase II antioxidant genes via Nrf2 activation, although the underlying mechanism has not been fully elucidated. In this study, we investigated Nrf2 induction in response to SFN in human bronchial epithelial BEAS-2B cells and determined the signaling pathways involved in this process. SFN treatment reduced cell viability. Prior to cell death, intracellular reactive oxygen species (ROS) were generated at a high rate within a minute of commencing SFN treatment. Pretreatment with antioxidant N-acetylcysteine (NAC) blocked SFN-induced decrease in cell growth. Erk1/2 was activated within 30 min of SFN addition, whereas Akt phosphorylation did not significantly change until the first 8 hr after SFN treatment but then became substantially low until 48 hr. Inhibition of Erk1/2 phosphorylation attenuated SFN-induced loss of cell viability. Nrf2 protein levels in both nuclear and whole cell lysates were increased by SFN treatment, which was dependent on ROS production. Knockdown of Nrf2 with siRNA attenuated SFN-induced heme oxygenase-1 (HO-1) up-regulation. Induction of the Nrf2/HO-1 after SFN treatment was potently suppressed by pretreatment with NAC. Overall, our results indicate that SFN mediates antioxidative and antiproliferative responses by generating ROS in BEAS-2B cells. PMID- 22065905 TI - Frequency of killer cell immunoglobulin-like receptors (KIRs) in Korean patients with chronic HCV infection. AB - Natural killer (NK) cells play an important role in innate immunity, especially in the response to viral infections, such as hepatitis C virus (HCV). Killer cell immunoglobulin-like receptors (KIRs) are the primary receptors of NK cells that mediate innate immunity. KIRs are also involved in acquired immunity, because some KIRs are expressed on the surface of certain subsets of T cells. In this study, the frequency of KIR genes, HLA-C allotypes, and combinations of KIR genes with their HLA-C ligands were evaluated in two different groups of the Korean population: controls and patients with chronic HCV infection. The study population consisted of 147 Korean patients with chronic HCV infection. The frequency of KIR2DS2 in patients with chronic HCV infection was 9.5% which was significantly lower than 19.5% of the control (P < 0.01). However, there were no significant differences in the frequency of other KIR genes, HLA-C allotypes or different combinations of KIR genes with their HLA-C ligands. This study can contribute to the further prospective study with a larger scale, suggesting the assumption that KIR2DS2 might aid in HCV clearance by enhancing both the innate and acquired immune responses of people in Korea. PMID- 22065906 TI - Apoptotic effects of genistein, biochanin-A and apigenin on LNCaP and PC-3 cells by p21 through transcriptional inhibition of polo-like kinase-1. AB - Natural isoflavones and flavones are important dietary factors for prostate cancer prevention. We investigated the molecular mechanism of these compounds (genistein, biochanin-A and apigenin) in PC-3 (hormone-independent/p53 mutant type) and LNCaP (hormone-dependent/p53 wild type) prostate cancer cells. A cell growth rate and apoptotic activities were analyzed in different concentrations and exposure time to evaluate the antitumor activities of genistein, biochanin-A and apigenin. The real time PCR and Western blot analysis were performed to investigate whether the molecular mechanism of these compounds are involving the p21 and PLK-1 pathway. Apoptosis of prostate cancer cells was associated with p21 up-regulation and PLK-1 suppression. Exposure of genistein, biochanin-A and apigenin on LNCaP and PC-3 prostate cancer cells resulted in same pattern of cell cycle arrest and apoptosis. The inhibition effect for cell proliferation was slightly greater in LNCaP than PC-3 cells. In conclusion, flavonoids treatment induces up-regulation of p21 expression, and p21 inhibits transcription of PLK-1, which promotes apoptosis of cancer cells. PMID- 22065907 TI - Protective effect of hypoxic preconditioning on hypoxic-ischemic injured newborn rats. AB - Brief episodes of cerebral hypoxia-ischemia cause transient ischemic tolerance to subsequent ischemic events that are otherwise lethal. This study was conducted to evaluate the protective effect of hypoxic preconditioning on hypoxic-ischemic injury in the neonatal rat and the persistence of a protective window after hypoxic preconditioning. The rats were preconditioned with hypoxia (8% oxygen, 92% nitrogen) for three hours, subjected to ischemia using ligation of the right common carotid artery, and then exposed to another three hours of hypoxia. Using proton magnetic resonance spectroscopy, terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end-labeling (TUNEL) staining, and morphologic scores, this study shows that hypoxic preconditioning 6-hr to 1-day before hypoxic ischemic injury increases survival rates and has neuroprotective effects against subsequent hypoxic-ischemic injury. The mechanism of the protective effects of hypoxic preconditioning in the newborn rat brain may involve downregulation of apoptotic cell death. PMID- 22065908 TI - Orthopedic surgeon's awareness can improve osteoporosis treatment following hip fracture: a prospective cohort study. AB - Through retrospective Jeju-cohort study at 2005, we found low rates of detection of osteoporosis (20.1%) and medication for osteoporosis (15.5%) in those who experienced hip fracture. This study was to determine the orthopedic surgeons' awareness could increase the osteoporosis treatment rate after a hip fracture and the patient barriers to osteoporosis management. We prospectively followed 208 patients older than 50 yr who were enrolled for hip fractures during 2007 in Jeju cohort. Thirty four fractures in men and 174 in women were treated at the eight hospitals. During the study period, orthopedic surgeons who worked at these hospitals attended two education sessions and were provided with posters and brochures. Patients were interviewed 6 months after discharge using an evaluation questionnaire regarding their perceptions of barriers to osteoporosis treatment. The patients were followed for a minimum of one year. Ninety-four patients (45.2%) underwent detection of osteoporosis by dual energy x-ray absorptiometry and 67 (32.2%) were prescribed medication for osteoporosis at the time of discharge. According to the questionnaire, the most common barrier to treatment for osteoporosis after a hip fracture was patients reluctance. The detection and medication rate for osteoporosis after hip fracture increased twofold after orthopedic surgeons had attended the intervention program. Nevertheless, the osteoporosis treatment rate remains inadequate. PMID- 22065909 TI - Plexiform angiomyxoid myofibroblastic tumor of the stomach: a case report. AB - Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a recently described mesenchymal tumor of the stomach. We report the first case of PAMT in Korea. A 52 yr-old man underwent esophagogastroduodenoscopy due to dyspepsia for 2 yr. There was a submucosal mass with small mucosal ulceration in the gastric antrum. The tumor measured 3.5 * 2.3 cm in size and showed multinodular plexiform growth pattern of bland-looking spindle cells separated by an abundant myxoid or fibromyxoid matrix rich in small thin-walled blood vessels. The tumor cells were negative for CD117 (c-KIT), CD34 and S-100 protein, but diffusely positive for smooth muscle actin consistent with predominant myofibroblastic differentiation. The patient is doing well without recurrence or metastasis for 5 months after surgery. Although there have been limited follow-up data, PAMT is regarded as a benign gastric neoplasm with histological and immunohistochemical characteristics distinguished from gastrointestinal stromal tumor and other mesenchymal tumors of the stomach. PMID- 22065910 TI - Use of drug-eluting stent with provisional T-stenting technique in the treatment of renal artery bifurcation stenosis; long-term angiographic follow-up. AB - Atherosclerotic renal artery stenosis (RAS) usually involves the ostium and the proximal one-third of the renal artery main branch. Percutaneous renal artery angioplasty with stent placement is a well recognized treatment for atherosclerotic RAS. Occasionally, atherosclerotic RAS involves renal artery bifurcations. However, stent implantation in atherosclerotic RAS involving bifurcation is not only troublesome, but also challenging because of side branch occlusion and in-stent restenosis (ISR). In the present report, we describe the use of drug-eluting stents (DES) with provisional T-stenting technique for the treatment of renal artery bifurcation lesion. Follow-up angiogram showed no significant ISR 18 months after the procedure. In the treatment of renal bifurcation lesions, a two-stent strategy using DES could be a viable option in selected patients. PMID- 22065911 TI - Dura mater graft-associated Creutzfeldt-Jakob disease: the first case in Korea. AB - Since 1987, dura mater graft-associated iatrogenic Creutzfeldt-Jakob disease (dCJD) has been reported in many countries. We report the first case of dCJD in Korea. A 54-yr-old woman, who underwent resection of the meningioma in the left frontal region and received a dura mater graft 23 yr ago presented with dysesthesia followed by psychiatric symptoms and ataxia. Her neurological symptoms rapidly progressed to such an extent that she exhibited myoclonus, dementia, and pyramidal and extrapyramidal signs within 8 weeks. The 14-3-3 protein was detected in her cerebrospinal fluid; however, an electroencephalogram did not reveal characteristic positive sharp wave complexes. Diffusion-weighted magnetic resonance images, obtained serially over 64 days, revealed the rapid progression of areas of high signal intensity in the caudate nucleus and cingulate gyrus to widespread areas of high signal intensity in the cortex and basal ganglia. Pathological examination of brain biopsy specimens confirmed the presence of spongiform changes and deposition of prion protein in the neurons and neuropils. PMID- 22065912 TI - Recurrent bilateral branch retinal artery occlusion with hearing loss and encephalopathy: the first case report of Susac syndrome in Korea. AB - We report the first case of Susac syndrome in Koreans, in a 23-yr-old female patient who presented with sudden visual loss and associated neurological symptoms. Ophthalmic examination and fluorescein angiography showed multiple areas of branch retinal artery occlusion, which tended to recur in both eyes. Magnetic resonance imaging showed dot-like, diffusion-restricted lesions in the corpus callosum and left fornix, and audiometry showed low-frequency sensory hearing loss, compatible with Susac syndrome. She received immunosuppressive therapy with oral steroid and azathioprine. Three months later all the symptoms disappeared but obstructive vasculitis have been relapsing. This patient demonstrated the entire clinical triad of Susac syndrome, which tends to occur in young females. Although this disorder has rarely been reported in Asian populations, a high index of suspicion is warranted for early diagnosis and timely treatment. PMID- 22065913 TI - Early non-invasive diagnosis and treatment of acute eosinophilic myopericarditis by cardiac magnetic resonance. AB - We report a case of early non-invasive diagnosis of acute eosinophilic myopericarditis (AEM) by cardiovascular magnetic resonance (CMR) before cardiac biopsy. A 35-yr-old woman presented with a flu-like illness, followed by pleuritic chest pain and shortness of breath. Transthoracic echocardiography revealed mild left ventricular (LV) systolic dysfunction with borderline LV wall thickness and moderate pericardial effusion. The patient had peripheral eosinophilia and CMR was performed immediately at first day of visit before cardiac biopsy. CMR showed diffuse subepicardial high T2 signals and diffuse late gadolinium enhancement in LV. Steroid therapy was immediately initiated and patient's symptom was rapidly improved. Endomyocardial biopsy at hospital day 3 reported multifocal mild infiltration of eosinophils and lymphocytes. The patient was finally confirmed as acute eosinophilic myopericarditis. This presentation emphasizes on the role of CMR which enables early non-invasive diagnosis of AEM and visualize the extent of the myocarditis. PMID- 22065914 TI - Polymorphisms in apoptosis-related genes and TP53 mutations in non-small cell lung cancer. AB - Apoptosis plays an essential role in the elimination of mutated or transformed cells from the body. Therefore, polymorphisms of apoptosis-related genes may lead to an alteration in apoptotic capacity, thereby affecting the occurrence of TP53 mutations in lung cancer. We investigated the relationship between potentially functional polymorphisms of apoptosis-related genes and TP53 mutations in non small cell lung cancer (NSCLC). Twenty-seven single nucleotide polymorphisms in 20 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay in 173 NSCLCs and the associations with TP53 mutations in the entire coding exons (exons 2-11), including splicing sites of the gene, were analyzed. None of the 27 polymorphisms was significantly associated with the occurrence of TP53 mutations. This suggests that apoptosis-related genes may not play an important role in the occurrence of TP53 mutations in lung cancer. PMID- 22065916 TI - Protein changes in the retina following experimental retinal detachment in rabbits. AB - PURPOSE: Retinal detachment leads to the widespread cellular remodeling of the retina. The purpose of this study was to identify protein changes that accompany these cellular alterations by comparing the proteomic profiles of sham and experimentally detached rabbit retina. Elucidation of the proteins most dramatically affected by retinal detachment would add further understanding to the pathophysiology of this condition, and potentially identify therapeutic targets useful in preventing the deleterious effects of detachment, including photoreceptor cell death and the activation of non-neuronal microglial and Muller cells. METHODS: Retinal detachments were induced in the right eyes of six New Zealand Red pigmented rabbits. Sham surgery was performed in the right eyes of six other rabbits that were used as controls. At seven days, the eyes were enucleated and the retinal tissue was harvested. The individual retinal samples were subjected to high resolution two-dimensional polyacrylamide gel electrophoresis. Differentially expressed protein spots were processed for identification by liquid chromatography-tandem mass spectrometry. Further investigation was undertaken with western blotting, and immunocytochemical studies on a further set of four sham and four detached retinas. RESULTS: Eighteen protein spots were found to be at least twofold differentially expressed between the sham and detached retinas. These protein spots were identified as: vimentin; tubulin beta-2C; fragments of alpha-enolase; fructose-bisphosphate aldolase A; ATP synthase subunit beta; mitochondrial creatine kinase; N-terminal fragments of albumin; prohibitin; and transducin-beta(1). CONCLUSIONS: The differentially expressed proteins determined in this study may play an important role in the cellular responses of the retina after its detachment, subsequent ability to recover following surgical reattachment, as well as in serious complications such as subretinal fibrosis and proliferative vitreoretinopathy. PMID- 22065917 TI - Evaluation of topical cysteamine therapy in the CTNS(-/-) knockout mouse using in vivo confocal microscopy. AB - PURPOSE: The purpose of this study was to assess the ability of quantitative in vivo confocal microscopy (CM) to detect changes in cystine crystal volume in the cystinosisn (Ctns(-/-))mouse cornea following topical cysteamine therapy. METHODS: Fifteen Ctns(-/-) mice were sequentially followed using in vivo CM from 3 to 10 months of age. In a second experiment, five mice receiving topical cysteamine eyedrops (0.55%) for 4 weeks were compared to five untreated mice. The volume of corneal cystine crystals was determined by thresholding and counting high intensity pixels in the in vivo CM scans and dividing by the stromal volume to calculate a crystal volume index (CVI). RESULTS: Corneal crystals progressively increased in density with age, reaching a peak density at 6-8 months and showing a 70 fold increase in CVI. Eyes treated with cysteamine drops showed significantly less crystal accumulation compared to control eyes (p<0.001) with only a 15% increase in treated eyes (p=ns) compared to 173% increase (p<0.04) for untreated eyes. CONCLUSIONS: Measurement of CVI shows that there is a progressive increase in cystine crystal volume up to 8 months of age and that cysteamine eyedrops significantly inhibits progression in the Ctns(-/-) mouse. These findings are similar to those seen clinically in patients with cystinosis, and suggest that measurement of CVI in the Ctns(-/-) mouse may be used as a model to develop novel therapeutic strategies for treating corneal cystinosis. PMID- 22065918 TI - CFH 184G as a genetic risk marker for anterior uveitis in Chinese females. AB - OBJECTIVE: To investigate the association of three single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), KIAA1109, and interleukin 27 (IL-27) genes in patients with anterior uveitis (AU). METHODS: A case-control study was performed in 98 Chinese AU patients and 308 healthy controls. Three SNPs including CFH-rs800292, KIAA1109-rs4505848, and IL27-rs4788084 were detected using TaqMan SNP Genotyping Assays. Analyses were also stratified according to gender, clinical features and human leukocyte antigen (HLA)-B27 status of the patients. RESULTS: No significant association was found between all three SNPs and AU. However, when stratified by gender, there were significant increases in the frequency of the CFH-rs800292 184G allele and GG homozygosity in female patients compared with control subjects (p=0.003 and p=0.009, respectively). Similar association was not detected in males. No significant association was found between AU and KIAA1109-rs4505848 or IL27-rs4788084 even stratified by gender. There was no significant difference in genotypes of AU patients stratified by various clinical features. Subgroup analyses showed that all three SNPs (rs800292, rs4505848, and rs4788084) were not associated with AU in HLA-B27 positive patients, neither in HLA-B27-negative patients. CONCLUSIONS: Our results showed an association between AU and CFH polymorphism in Chinese female patients but not in males, indicating gender-specific genetic differences in CFH. Gender should be considered in genetic studies of anterior uveitis even extending to other immunologic diseases. PMID- 22065919 TI - Combined treatment with antioxidants and immunosuppressants on cytokine release by human peripheral blood mononuclear cells - chemically injured keratocyte reaction. AB - PURPOSE: To investigate the effect of antioxidants and immunosuppresants on mixed peripheral blood mononuclear cells (PBMC) - chemically injured keratocytes reaction (MLKR). METHODS: The PBMC stimulation assay was performed using chemically injured keratocytes treated with 0.05 N NaOH for 90 s (MLKR). MLKR were treated with various drugs including rapamycin, dexamethasone, mycophenoleic acid (MPA), alpha lipoic acid (ALA), and N-acetyl cysteine (NAC). Matrix metalloprotease-9 (MMP-9), transforming growth factor-beta 1 (TGF-beta1), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF) secretion profiles of activated PBMCs stimulated by NaOH-treated keratocytes were determined by ELISA. RESULTS: Anti-oxidants as well as immunosuppressants suppressed PBMC proliferation. MMP-9 levels were lower in antioxidants group. IL 6 levels decreased in dexamethasone group and anti-oxidants group. Combination of immunosuppressants and antioxidants suppressed more PBMC proliferation except for rapamycin + ALA group, suppressed MMP-9 production except for MPA + ALA group, decreased IL-6 levels and increased MIF levels except for rapamycin + ALA group. TGF-beta1 levels were elevated in rapamycin group and rapamycin + ALA group. CONCLUSIONS: Cytokine production was different depending on combination of drugs.Our results suggest that the different drugs should be selected for treatment according to the phases of corneal chemical burn. PMID- 22065920 TI - Age-related retention of fiber cell nuclei and nuclear fragments in the lens cortices of multiple species. AB - PURPOSE: To determine the differences between species in the retention of lens fiber cell nuclei and nuclear fragments in the aging lens cortex and the relationship of nuclear retention to lens opacity. For this purpose old human, monkey, dog, and rat lenses were compared to those of three strains of mouse. We also investigated possible mechanisms leading to nuclear retention. METHODS: Fixed specimens of the species referred to above were obtained from immediate on site sacrifice of mice and rats, or from recently fixed lenses of other species, dogs, monkeys, and humans, obtained from collaborators. The retention of undegraded nuclei and nuclear fragments was graded 1-4 from histologic observation. All species lenses were examined microscopically in fixed sections stained with hematoxylin and eosin (H&E) or 4',6-diamidino-2-phenylindole (DAPI). Slit lamp observations were made only on the mice and rats before sacrifice and lens fixation. Values of 0 to 4 (clear lens to cataract) were given to degree of opacity. MRNA content in young versus old C57BL/6 mouse lenses was determined by quantitative PCR (qPCR) for DNase II-like acid DNase (DLAD) and other proteins. DLAD protein was determined by immunofluorescence of fixed eye sections. RESULTS: In old C57BL/6 and DBA mice and, to a lesser degree, in old CBA mice and old Brown Norway (BN) rats lenses were seen to contain a greatly expanded pool of unresolved whole nuclei or fragments of nuclei in differentiating lens fiber cells. This generally correlated with increased slit lamp opacities in these mice. Most old dog lenses also had an increase in retained cortical nuclei, as did a few old humans. However, a second rat strain, BNF1, in which opacity was quite high had no increase in retained nuclei with age nor did any of the old monkeys, indicating that retained nuclei could not be a cause of opacity in these animals. The nuclei and nuclear fragments were located at all levels in the outer cortex extending inward from the lens equator and were observable by the DAPI. These nuclei and nuclear fragments were seen from 12 months onward in all C57BL/6 and DBA/2 mice and to a lesser degree in the CBA, increasing in number and in space occupancy with increasing age. Preliminary results suggest that retention of nuclei in the C57BL/6 mouse is correlated with an age-related loss of DLAD from old lenses. CONCLUSIONS: A very marked apparently light refractive condition caused by retained cortical nuclei and nuclear fragments is present in the lens cortices, increasing with age in the three strains of mice examined and in one of two strains of rats (BN). This condition was also seen in some old dogs and a few old humans. It may be caused by an age-related loss of DLAD, which is essential for nuclear DNA degradation in the lens. However, this condition does not develop in old BNF1 rats, or old monkeys and is only seen sporadically in humans. Thus, it can not be a universal cause for age related lens opacity or cataract presence, although it develops concurrently with opacity in mice. This phenomenon should be considered when using the old mouse as a model for human age-related cataract. PMID- 22065921 TI - A mutation in the UBIAD1 gene in a Han Chinese family with Schnyder corneal dystrophy. AB - PURPOSE: To identify the molecular defect in the UbiA prenyltransferase domain containing 1 (UBIAD1) gene in a four-generation Chinese family with Schnyder corneal dystrophy (SCD). METHODS: A four-generation Chinese family with SCD and 50 unrelated normal individuals as controls were enrolled in. The complete ophthalmic examination was performed and blood samples were taken for subsequent genetic analysis. Mutation screening of UBIAD1 was performed by polymerase chain reaction (PCR) based DNA sequencing. RESULTS: The missense mutation N102S in UBIAD1 was identified in this pedigree from the mainland of China for the first time. The molecular defect cosegregates with the affected individuals, whereas not found in unaffected family members or normal controls. CONCLUSIONS: The nonsynonymous mutation, N102S, in UBIAD1 detected in this family confirms that it is a mutation hot spot not only in Caucasian but also in Chinese. This finding adds support to the proposal that N102S has been independently mutated and argues against the likelihood of a founder effect. PMID- 22065922 TI - Congenital anterior polar cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. AB - PURPOSE: To identify the potential pathogenic mutation over four generations of a Chinese family with congenital anterior polar cataracts (APC). METHODS: We investigated four generations of a Chinese family who are afflicted with anterior polar cataracts. The family resides in a relatively isolated region of Northern China. Peripheral blood samples were collected from all of the family members, and genomic DNA was then extracted from the blood samples. A gene scan was performed using about 400 primers labeled with fluorescent stain. Linkage software defined the region of the diseased gene with a Linkage analysis, and Cyrillic software processed the resulting haplotypes. Mutation detection was performed in the candidate gene by sequencing amplified products. RESULTS: A maximum logarithm of odds score (LOD) score was obtained at marker D21S1252(LOD score [Z]=3.23, recombination fraction [theta]=0.0. Haplotype analysis traced the disease gene to an 18.47 cM region bounded by D21S263 and D21S266 on chromosome21q22.11-q22.3. Direct sequencing of the candidate alpha A crystallin (CRYAA) gene revealed a c.347G>A transition in exon 3 of CRYAA that co-segregated with the cataract in the family members and was not observed in 100 control patients. This single-nucleotide change resulted in the substitution of a highly conserved Arginine by Histidine (R116H). CONCLUSIONS: The present study identified a missense mutation (R116H) in the CRYAA gene that causes autosomal dominant congenital anterior polar cataracts in a Chinese family. Our finding confirms the high rate of apparently independent mutations at this dinucleotide. PMID- 22065923 TI - Interaction between Pax6 and its novel mutant in Bufo raddei Strauch. AB - PURPOSE: Exploration of the relationship between a novel paired box 6 (Pax6) mutant and Pax6 in Bufo raddei Strauch. METHODS: RT-PCR, yeast 2-hybrid system, and co-immunoprecipitation were used to analyze the Pax6 protein and its mutant during embryonic eye development in Bufo raddei Strauch. RESULTS: We have cloned the Pax6 ORF sequence from Bufo raddei Strauch. Here we report the cloning of a novel Pax6 homolog of Bufo raddei Strauch named Pax6 variant. Comparing the 2 genes, the homolog of ORF nucleotide sequence is more than 99% in Bufo raddei Strauch; only the proline-serine-threonine(PST)-rich transaction domain differs. The deduced amino acid sequences of PST region are 53.1% identical. An interaction was found between Pax6 and Pax6 variant via yeast 2-hybrid system; with further study, we found that they interacted in vivo via co immunopricipitation. CONCLUSIONS: A Pax6 mutant was first found in Bufo raddei Strauch. Interaction between Pax6 and Pax6 variant may play a critical role during eye development in Bufo raddei Strauch. This suggests that expression of Pax6 variant may play a role and appears to be a necessity in eye development, but that Pax6 itself is still pivotal in eye development. PMID- 22065924 TI - RDH12 retinopathy: novel mutations and phenotypic description. AB - PURPOSE: To identify patients with autosomal recessive retinal dystrophy caused by mutations in the gene, retinal dehydrogenase 12 (RDH12), and to report the associated phenotype. METHODS: After giving informed consent, all patients underwent full clinical evaluation. Patients were selected for mutation analysis based upon positive results from the Asper Ophthalmics Leber congenital amaurosis arrayed primer extansion (APEX) microarray screening, linkage analysis, or their clinical phenotype. All coding exons of RDH12 were screened by direct Sanger sequencing. Potential variants were checked for segregation in the respective families and screened in controls, and their pathogenicity analyzed using in silico prediction programs. RESULTS: Screening of 389 probands by the APEX microarray and/or direct sequencing identified bi-allelic mutations in 29 families. Seventeen novel mutations were identified. The phenotype in these patients presented with a severe early-onset rod-cone dystrophy. Funduscopy showed severe generalized retinal pigment epithelial and retinal atrophy, which progressed to dense, widespread intraretinal pigment migration by adulthood. The macula showed severe atrophy, with pigmentation and yellowing, and corresponding loss of fundus autofluorescence. Optical coherence tomography revealed marked retinal thinning and excavation at the macula. CONCLUSIONS: RDH12 mutations account for approximately 7% of disease in our cohort of patients diagnosed with Leber congenital amaurosis and early-onset retinal dystrophy. The clinical features of this disorder are highly characteristic and facilitate candidate gene screening. The term RDH12 retinopathy is proposed as a more accurate description. PMID- 22065925 TI - Zebularine suppresses TGF-beta-induced lens epithelial cell-myofibroblast transdifferentiation by inhibiting MeCP2. AB - PURPOSE: Posterior capsular opacification (PCO) is a common long-term complication of modern cataract surgery. Remnant lens epithelial cells (LECs) undergo a myofibroblast transdifferentiation that is thought to be the initial step of PCO pathogenesis. The purpose of this study is to determine the effects of zebularine on transforming growth factor-beta (TGFbeta)-induced, LEC myofibroblast transdifferentiation. METHODS: The expression levels of methyl CpG binding protein 2 (MeCP2) and alpha-smooth muscle actin (alpha-SMA) in human PCO membranes were evaluated by confocal microscopy. The role that MeCP2 played in TGFbeta2-induced alpha-SMA expression was analyzed by western blotting both before and after MeCP2 knockdown with MeCP2-specific siRNA. The effect of zebularine on MeCP2 expression was analyzed over time using a variety of dosages. The effect of zebularine on TGFbeta2-induced alpha-SMA expression was determined by western blot analysis. RESULTS: MeCP2 and alpha-SMA co-localized in human PCO membranes. When MeCP2 was depleted, TGFbeta2 could not induce alpha-SMA expression. Zebularine decreased MeCP2 expression in lens epithelial cells in a time- and dose-dependent pattern and reversed TGFbeta2-induced alpha-SMA expression. CONCLUSIONS: MeCP2 plays an important role in TGFbeta2-induced alpha SMA expression in lens epithelial cells. Zebularine could reverse the TGFbeta2 induced alpha-SMA expression by inhibiting MeCP2 expression. Therefore, zebularine could potentially prevent PCO formation. PMID- 22065926 TI - Enhanced in vitro antiproliferative effects of EpCAM antibody-functionalized paclitaxel-loaded PLGA nanoparticles in retinoblastoma cells. AB - BACKGROUND: To specifically deliver paclitaxel (PTX) to retinoblastoma (RB) cells, the anionic surface-charged poly(lactic-co-glycolic acid) (PLGA) NPs loaded with paclitaxel were conjugated with epithelial cell adhesion molecule (EpCAM) antibody for enhancing site-specific intracellular delivery of paclitaxel against EpCAM overexpressing RB cells. METHODS: PTX-loaded PLGA NPs were prepared by the oil-in-water single emulsion solvent evaporation method, and the PTX content in NPs was estimated by the reverse phase isocratic mode of high performance liquid chromatography. Ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride/N-hydroxysuccinimide chemistry was employed for the covalent attachment of monoclonal EpCAM antibody onto the NP surface. In vitro cytotoxicity of native PTX, unconjugated PTX-loaded NPs (PTX-NPs), and EpCAM antibody-conjugated PTX-loaded nanoparticles (PTX-NP-EpCAM) were evaluated on a Y79 RB cell line by a dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while cellular apoptosis, cysteinyl-aspartic acid protease (caspase)-3 activation, Poly (adenosine diphosphate-ribose) polymerase (PARP) cleavage, and cell-cycle arrest were quantified by flow cytometry. By employing flow cytometry and fluorescence image analyses, the extent of cellular uptake was comparatively evaluated. RESULTS: PTX-NP-EpCAM had superior antiproliferation activity, increased arrested cell population at the G(2)-M phase, and increased activation of caspase-3, followed by PARP cleavage in parallel with the induction of apoptosis. Increased uptake of PTX-Np-EpCAM by the cells suggests that they were mainly taken up through EpCAM mediated endocytosis. CONCLUSIONS: EpCAM antibody functionalized biodegradable NPs for tumor-selective drug delivery and overcoming drug resistance could be an efficient therapeutic strategy for retinoblastoma treatment. PMID- 22065927 TI - The human Muller cell line MIO-M1 expresses opsins. AB - PURPOSE: To determine whether the human Muller cell line Moorfields/Institute of Ophthalmology-Muller 1 (MIO-M1) expresses opsins. METHODS: The gene expression of opsins was determined by reverse-transcription PCR (RT-PCR). The presence of opsin proteins was determined by western blotting and immunocytochemistry. The light sensitivity of the cells was examined with imaging experiments using the calcium-sensitive dye Fluo-4. RESULTS: MIO-M1 cells express glial (glutamine synthase [GLUL], vimentin [VIM], glial fibrillary acidic protein [GFAP], cellular retinaldehyde-binding protein [RLBP1], glial high-affinity glutamate transporter [SLCA1], aquaporin-4 [AQP4], inwardly rectifying potassium channel Kir4.1 [Kir4.1]), neuronal (Thy-1 cell surface antigen [THY1], heavy neurofilament polypeptide [NEFH], microtubule-associated protein 2 [MAP2], neurogenic differentiation 1 [NEUROD1], neuronal nuclei [NEUN]), and neural progenitor markers (Nestin [NES], paired-type homeobox transcription factor [PAX6], neurogenic locus notch homolog 1 [NOTCH1]). The cells contain mRNA for the following opsins: blue opsin (OPN1SW), rhodopsin (OPN2), panopsin (OPN3), melanopsin (OPN4), neuropsin (OPN5), and peropsin (RRH), as well as for the transducins (guanine nucleotide binding protein [GNAZ], alpha transducing activity polypeptide 1 [GNAT1], alpha transducing activity polypeptide 2 [GNAT2]). The presence of blue opsin and melanopsin was confirmed with immunocytochemistry and western blotting. The immunoreactivity and mRNA of red green opsin were found in some but not all cultures, while the immunoreactivity for rhodopsin was absent in all cultures investigated. Repetitive stimulation with 480 nm light evoked slow and fast transient calcium responses in the majority of cells investigated, while irradiation with 600 nm light was ineffective. CONCLUSIONS: The human Muller cell line MIO-M1 expresses opsins. This suggests immortalized Muller cells could be used as a cellular source to produce human opsins for their potential application as therapeutic agents in patients with retinitis pigmentosa. PMID- 22065928 TI - Analysis of candidate genes for age-related macular degeneration subtypes in the Japanese population. AB - PURPOSE: Age-related macular degeneration (AMD) is thought to be a polygenetic disease. It is divided into three subtypes; neovascular AMD (nAMD), polypoidal choroidal vasculopathy, and retinal angiomatous proliferation (RAP). These subtypes are thought to have different pathophysiological and genetic backgrounds. We aimed to investigate the relationships between single nucleotide polymorphisms (SNPs) in candidate genes and subtypes of AMD in the Japanese population. METHODS: We genotyped 685 AMD patients and 277 controls for four SNPs of the selected candidate genes: rs800292 in complement factor H, rs10490924 in age-related maculopathy susceptibility 2 (ARMS2), rs2301995 in elastin (ELN), and rs1801133 in methylenetetrahydrofolate reductase (MTHFR). Case-control studies were performed using these AMD subtypes. Logistic regression analysis was performed using a history of hypertension, diabetes mellitus, and smoking as cardiovascular risks. RESULTS: The genotype-dominant or recessive distribution of all four SNPs differed significantly between the controls and the AMD patients. In the subtype analysis, there were significant differences between the controls and the AMD patients in genotype distributions. This was true for all AMD subtype analyses of both rs800292 (complement factor H) and rs10490924 (ARMS2). Logistic regression analysis indicated the TT genotype of the ARMS2 gene to be significantly more common in RAP patients (p=1.54*10(-13), odds ratio: 22.18). In contrast, there were significant differences in the genotype distribution between the controls and nAMD patients only for rs2301995 (ELN, p=0.022) and rs1801133 (MTHFR, p=2.50*10(-3)). CONCLUSIONS: Our results indicate that SNPs of the ARMS2 gene may serve as strong genetic markers of RAP, and that SNPs of the ELN and MTHFR genes are potential genetic markers for nAMD. PMID- 22065929 TI - Effects of a myosin light chain kinase inhibitor on the optics and accommodation of the avian crystalline lens. AB - PURPOSE: While many studies investigate the cytoskeletal properties of the lens with respect to cataract development, examinations of how these molecular structures interact are few. Myosin light chain kinase (MLCK), actin, and myosin are present on the crystalline lenses of chickens. The purpose of this experiment was to determine whether contractile proteins found on the lens play a role in the optical functions of the lens at rest, and during accommodation. METHODS: Eyes of 6-day old white Leghorn chicks (Gallus gallus domesticus) were enucleated, with the ciliary nerve intact. One eye was treated with the MLCK inhibitor 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-7) and the other eye with vehicle only. Three concentrations of ML-7 were used: 1 uM, 10 uM, and 100 uM. The back vertex focal lengths (BVFLs) were measured before, during, and after accommodation using an optical laser scanning monitor (ScantoxTM). To further confirm ML-7 activity, western blotting was performed to detect whether MLCK was inhibited. RESULTS: Western blots confirmed that MLCK was inhibited at all three ML-7 concentrations. Ten uM ML-7 treatments led to longer BVFLs at rest (p=0.0338), while 100 uM treatments led to opposite changes, resulting in shorter BVFLs (p=0.0220). While 1 uM treatments did not lead to significant optical changes (p=0.4416), BVFLs were similar in pattern to those of the 10 uM group. ML-7 had no effects on accommodative amplitudes (p=0.7848). CONCLUSIONS: Inhibition of MLCK by ML-7 led to differential changes in BVFLs that presumably affected lenticular integrity. No apparent effect on accommodative amplitudes was observed. PMID- 22065930 TI - A novel frame-shift mutation in FRMD7 causes X-linked idiopathic congenital nystagmus in a Chinese family. AB - PURPOSE: To screen mutations in the FERM domain-containing 7 (FRMD7) gene in a Chinese family with X-linked idiopathic congenital nystagmus (ICN). METHODS: It has been reported that FRMD7 mutations account for approximately 47% of X-linked nystagmus in Chinese patients. We collected 5 ml of blood samples from members of a family with X-linked ICN and 100 normal controls. Mutations in FRMD7 were determined by sequencing PCR products. RESULTS: We identified a previously unreported 4 bp deletion in FRMD7 (c.1486-1489 del TTTT) in a Chinese family. The mutation co-segregated with the disease phenotype in patients and female carriers, while it was not detected in other relatives or in the 100 normal controls. CONCLUSIONS: Our results expand the spectrum of FRMD7 mutations causing ICN, and further confirm the role of FRMD7 in the pathogenesis of ICN. Direct sequencing of FRMD7 could be used as a diagnostic testing of idiopathic congenital nystagmus. PMID- 22065931 TI - Decreased total antioxidants status in the plasma of patients with pseudoexfoliation glaucoma. AB - PURPOSE: To evaluate total antioxidant status (TAS) in the plasma of pseudoexfoliation glaucoma (PEG) patients and to compare this level with a matching control group. Additionally, we aim to investigate the effect of the combined action of the lysyl oxidase-like 1 (LOXL1) mutation status with TAS level on the development of PEG. METHODS: Plasma samples were obtained from 54 PEG patients and 54 controls of matching age, sex, and ethnicity. TAS in all samples was determined by spectrophotometric and enzyme-linked immunosorbent assay methods. The coding region of LOXL1, where it encompasses both single nucleotide polymorphisms (SNPs; rs1048661 and rs3825942), was sequenced. RESULTS: The mean (+/-SD) total antioxidant (TAS) value was lower among patients: 0.87 (0.24), range 0.9-1.41 than controls: 1.07 (0.23), range 0.72-1.94, and this difference was statistically significant (p<0.0001: 95%CI: -0.295-0.114). Evaluating the impact of age, sex, and the mutation in addition to the mean TAS value in patients with PEG, a logistic regression analysis was conducted using diseased/not diseased as the outcome of interest (the dependent variable). Results show that, controlling for all other variables, mean TAS value (p<0.0001) and the mutation G/G in rs3825942 (p=0.041) are significant risk factors for PEG. CONCLUSIONS: Our findings provide evidence that TAS decreases in the plasma of PEG patients, suggesting that TAS may have an important role in the pathogenesis of PEG. The combined effect of the "G" allele and the decreased TAS may contribute to the overall pathogenesis of PEG. PMID- 22065932 TI - A novel PIKFYVE mutation in fleck corneal dystrophy. AB - PURPOSE: To report the findings of the clinical and molecular evaluation in a Greek family with fleck corneal dystrophy (CFD). METHODS: A 58-year-old woman was seen on routine ophthalmic examination and diagnosed as having CFD. All available family members were examined to evaluate the clinical findings and inheritance of the disease. Twenty members of the family in five generations underwent slit-lamp examination. Eleven were females and nine males, aged from two years to 85 years old. Blood samples were available from four patients with CFD and seven unaffected relatives, and the DNAs were subjected to molecular screening of the phosphoinositide kinase, five finger-containing (PIKFYVE) gene by direct sequencing or denaturing high performance liquid chromatography (DHPLC). RESULTS: The clinical evaluation revealed six family members (five females and one male) with CFD. In two CFD patients early cataract formation was noticed. All patients affected with the corneal dystrophy were asymptomatic. The molecular analyses demonstrated the existence of a novel c.3060-3063delCCTT (p.P968Vfs23) mutation in PIKFYVE in all CFD patients tested but in none of the six unaffected family members. No molecular screening was performed in the seventh unaffected member as the causative mutation was clearly transmitted from his affected wife to his affected son. CONCLUSIONS: We report on the clinical and molecular findings of a five generation Greek family with CFD and we conclude that the novel c.3060 3063delCCTT (p.P968Vfs23) mutation in PIKFYVE, which segregated with the disease, was the causative mutation in this family. PMID- 22065933 TI - Increased response to oxidative stress challenge in Graves' ophthalmopathy orbital fibroblasts. AB - PURPOSE: To investigate whether orbital fibroblasts from patients with Graves' ophthalmopathy (GO) are more responsive to oxidative stress. METHODS: Lipid peroxidation, oxidative DNA damage, reactive oxygen species (ROS) contents and activities of antioxidant enzymes were measured in cultured orbital fibroblasts from GO patients and age-matched normal controls in response to 200 MUM hydrogen peroxide (H(2)O(2)). RESULTS: GO fibroblasts had increased basal levels of malondialdehyde (MDA), 8-hydroxy 2'-deoxyguanosine, superoxide anions, H(2)O(2), and manganese-dependent superoxide dismutase (Mn-SOD) activity, as well as decreased glutathione peroxidase (GPx) activity and the ratio between reduced (GSH) and oxidized glutathione (GSSG) compared with the orbital fibroblasts from normal subjects. After treatment of the cells with 200 MUM H(2)O(2), the amplitude of increase in the intracellular levels of MDA (63% versus 26%), H(2)O(2) (24% versus 13%) and Mn-SOD activity (48% versus 23%) was exaggerated in GO fibroblasts compared with normal controls, respectively. In addition, treatment of GO fibroblasts with 200 MUM H(2)O(2) led to a dramatic reduction of catalase activity (-59% versus -29%), GPx activity (-56% versus -13%), and GSH/GSSG ratio (-49% versus -21%), respectively. CONCLUSIONS: Elevated ROS and redox imbalance in GO orbital fibroblasts were exacerbated by H(2)O(2) as a result of exhaustion of GSH and compromise of antioxidant enzymes. Hypersensitivity to oxidative stress of GO orbital fibroblasts may play a role in the pathogenesis of GO. PMID- 22065934 TI - Fibroblast growth factor 10 upregulates the expression of mucins in rat conjunctival epithelial cells. AB - PURPOSE: This in vitro study aimed to gain insight into the function of fibroblast growth factor 10 (FGF10) on the ocular surface, especially its effect on mRNA expression of the mucins Muc1, Muc4, and Muc5ac, and mucin protein synthesis. METHODS: We isolated primary cultured rat conjunctival epithelial cells (Cj-ECs) and treated them with FGF10 (1 ng/ml, 10 ng/ml, 100 ng/ml, and 200 ng/ml) and basic fibroblast growth factor 2 (FGF2; 10 ng/ml) for 24 h or 48 h. The proliferation of Cj-ECs was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3 carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). mRNA levels of Muc1, Muc4, and Muc5ac were determined by real-time PCR. Synthesis levels of MUC1 and MUC4 were measured by western blot. Flow cytometry and Annexin V/PI double staining revealed degrees of apoptosis. RESULTS: In primary culture, the epithelial cells were compact and cobblestone pavement in shape. Most of the cells were positive for cytokeratin (CK). FGF10 and FGF2 significantly stimulated Muc1, Muc4, and Muc5ac mRNA expression, cell proliferation, and synthesis of MUC1 and MUC4 proteins. FGF10 was more potent than FGF2 in these regards. FGF10 did not restrain the apoptosis of Cj-ECs. CONCLUSIONS: The results of this study demonstrated that FGF10 is associated with the promotion of Cj-EC proliferation and mucin production. The effects of FGF10 on Cj-ECs support a rationale to investigate its therapeutic potential for ocular surface diseases. PMID- 22065935 TI - A tribute to Dr Naranjan S Dhalla on his 75th birthday. PMID- 22065936 TI - Trastuzumab-induced cardiac dysfunction: A 'dual-hit'. AB - Trastuzumab (Trz) is a monoclonal antibody against the human epidermal growth factor receptor 2 that is found to be overexpressed in 25% to 30% of breast cancer patients. In spite of the therapeutic benefits of Trz, cardiotoxic side effects are still an issue. This effect is potentiated particularly when Trz is administered following doxorubicin (DOX) treatment. Among the various mechanisms that may account for DOX and Trz-induced cardiotoxicity, the role of oxidative stress has gained significant support. The present review discusses the evidence supporting the hypothesis that oxidative stress comes from multiple sources through an increase in the production of reactive oxygen species and/or a decrease in antioxidant defense systems. The adjuvant use of Trz can potentiate cardiomyocyte damage through a 'dual-hit' mechanism, which includes inhibition of the neuregulin-1 survival signalling pathway and angiotensin II-induced activation of NADPH oxidase, with the ability to further increase reactive oxygen species production. Preventive therapies for DOX- and Trz-induced cardiac dysfunction have eluded investigators, but may include the prophylactic use of angiotensin-converting enzyme inhibitors, beta-blockers and use of antioxidants. Thus, a better understanding of the mechanisms leading to this characteristic drug-induced cardiomyopathy, as well as potential cardioprotective strategies is required. PMID- 22065937 TI - Effect of sarpogrelate on cardiovascular disorders. AB - The present article, dedicated to Dr NS Dhalla on the occasion of the jubilee of his life's work, is a brief review of articles based on the authors' studies of sarpogrelate conducted in collaboration with Dr NS Dhalla. These studies on the effects of sarpogrelate on cardiovascular disorders have been ongoing for more than 10 years, and 10 articles have been published to date. PMID- 22065939 TI - Prevention of diabetes-induced myocardial dysfunction in rats using the juice of the Emblica officinalis fruit. AB - Normalization of hyperglycemia, hyperlipidemia and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. The present study investigated the effects of the fruit juice obtained from Emblica officinalis on myocardial dysfunction in diabetic rats. Diabetes was induced by streptozotocin (STZ), and the rats were treated with E officinalis fruit juice for eight weeks. Injection of STZ produced loss of body weight, polydypsia, polyphagia, hyperglycemia, hypoinsulinemia and dyslipidemia. It also produced hypertension, bradycardia, hypertrophy and myocardial functional alterations associated with an increase in serum lactate dehydrogenase and creatinine kinase MB levels. Treatment with the fruit juice not only prevented STZ-induced loss of body weight, increases in water and food intake, increases in serum glucose levels and disturbed lipid profile, but also an increase in serum lactate dehydrogenase and creatinine kinase-MB levels, and increased myocardial hypertrophy and cardiomyopathy. There was an increase in the area under the curve (AUC) for glucose, and a decrease in AUC(insulin) was observed in diabetic rats; treatment decreased AUC(glucose) but not AUC(insulin) or hyperinsulinemia. There was a decrease in antioxidant enzyme levels (in superoxide dismutase, reduced glutathione and catalase) in diabetic hearts, which could be improved by treatment with fruit juice. The present data suggest that fruit juice may be beneficial for the treatment of myocardial damage associated with type 1 diabetes mellitus. The activity of E officinalis fruit juice can be attributed to the concentration of polyphenol present. PMID- 22065938 TI - An integrated approach for the mechanisms responsible for atherosclerotic plaque regression. AB - Atherosclerosis was originally considered to be an ongoing process that was inevitably associated with age. However, plaques are highly dynamic, and are able to progress, stabilize or regress depending on their surrounding milieu. A great deal of research attention has been focused on understanding the involvement of high-density lipoprotein in atherosclerotic plaque regression. However, atherosclerotic plaque regression encompasses a variety of processes that can be grouped into three main areas: removal of lipids and necrotic material; restoration of endothelial function and repair of denuded areas; and cessation of vascular smooth muscle cell proliferation and phenotype reversal. In addition to the role of high-density lipoproteins in lipid removal, resident macrophages and foam cells are able to regain motility and rapidly migrate on milieu improvement, moving both lipids and necrotic material to regional lymph nodes. Neighbouring endothelial cells can proliferate and replace dead and dysfunctional cells. Circulating endothelial progenitor cells can similarly restore vessel function. Finally, abrogation of smooth muscle cell proliferation occurs secondarily to these processes. This information is integrated in the current article to present a comprehensive and clear depiction of plaque regression. This integrated view of regression is essential to optimize the pharmaceutical targeting of the many processes and pathways involved in plaque regression. PMID- 22065940 TI - Effect of a glutathione S-transferase inhibitor on oxidative stress and ischemia reperfusion-induced apoptotic signalling of cultured cardiomyocytes. AB - Oxidative stress and ischemia-reperfusion (I/R) injury are crucial in the pathogenesis of cardiovascular diseases. The antioxidant glutathione S transferase (GST) is responsible for the high-capacity metabolic inactivation of electrophilic compounds and toxic substrates. The main objective of the present study was to examine the effect of GST inhibition (with the administration of ethacrynic acid [EA]) on the viability and apoptosis of cardiomyocytes when these cells are exposed to various stress components of I/R and mitogen-activated protein kinase (c-Jun N-terminal kinase, p38 and extracellular signal-regulated kinase [ERK]) inhibitors. The primary culture of neonatal rat cardiomyocytes was divided into six experimental groups: control group of cells (group 1), cells exposed to H(2)O(2) (group 2), I/R (group 3), I/R and EA (group 4), H(2)O(2) coupled with EA (group 5), and EA alone (group 6). The viability of cardiomyocytes was determined using a colorimetric MTT assay. The apoptosis ratio was evaluated via fluorescein isothiocyanate-labelled annexin V and propidium iodide staining. c-Jun N-terminal kinase, p38, Akt/protein kinase B and ERK/p42 p44 transcription factors were monitored with flow cytometry. c-Jun N-terminal kinase activation increased due to GST inhibition during I/R. EA administration led to a significant increase in p38 activation following both H(2)O(2) treatment and I/R. ERK phosphorylation increased when GST was exposed to I/R. A pronounced decrease in Akt phosphorylation was observed when cells were cotreated with EA and H(2)O(2). GST plays an important role as a regulator of mitogen-activated protein kinase pathways in I/R injury. PMID- 22065941 TI - MicroRNA signatures of stem cells. AB - The unique properties of embryonic stem (ES) cells to self-renew indefinitely or to differentiate to any cell type (pluripotency) warrants their clinical application in regenerative medicine. MicroRNAs are crucial for post transcriptional gene regulation and, thus, remain an essential element of the regulation of ES cells. The present review discusses the essential elements of microRNAs that regulate the life and death of ES cells. PMID- 22065942 TI - Effects of amino acid supplementation on myocardial cell damage and cardiac function in diabetes. AB - Although amino acid deficiencies are known to occur in diabetes patients and are considered to contribute to the occurrence of cardiomyopathy, the mechanisms of the impact of the restoration of amino acids on improved cardiac function are not completely understood. Accordingly, the present study was conducted to examine the beneficial effects of dietary supplementation of taurine, arginine and carnitine, individually or in combination, in an experimental model of chronic diabetes. For inducing diabetes, rats received a single injection of streptozotocin (65 mg/kg body weight). Experimental animals were treated (by oral gavage) daily for three weeks with amino acids before the induction of diabetes; this treatment was continued for an additional eight-week period. Diabetes was observed to induce cardiac dysfunction, myocardial cell damage, and changes in plasma glucose and lipid levels. Treatment of diabetic animals with taurine, unlike carnitine or arginine, attenuated alterations in cardiac function, as evidenced by echocardiography and in vivo catheterization techniques. Taurine, carnitine and arginine, individually or in combination, attenuated diabetes induced cell damage as revealed by electron microscopy. While carnitine alone reduced plasma levels of triglycerides with an increase in high-density lipoprotein cholesterol, none of the amino acids, alone or in combination, had an effect on myocardial glycogen content, lipid accumulation or hyperglycemia. These results suggest that dietary supplementation of taurine attenuates diabetes induced changes in cardiac contractile function and ultrastructure without any alterations in plasma lipid and glucose levels. PMID- 22065943 TI - Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress. AB - Chronic hypertension may have a negative impact on the myocardial response to ischemia. On the other hand, intrinsic ischemic tolerance may persist even in the pathologically altered hearts of hypertensive animals, and may be modified by short- or long-term adaptation to different stressful conditions. The effects of long-term limitation of living space (ie, crowding stress [CS]) and brief ischemia-induced stress on cardiac response to ischemia/reperfusion (I/R) injury are not yet fully characterized in hypertensive subjects. The present study was designed to test the influence of chronic and acute stress on the myocardial response to I/R in spontaneously hypertensive rats (SHR) compared with their effects in normotensive counterparts. In both groups, chronic, eight-week CS was induced by caging five rats per cage in cages designed for two rats (200 cm(2)/rat), while controls (C) were housed four to a cage in cages designed for six animals (480 cm(2)/rat). Acute stress was evoked by one cycle of I/R (5 min each, ischemic preconditioning) before sustained I/R in isolated Langendorff perfused hearts of normotensive and SHR rats. At baseline conditions, the effects of CS were manifested only as a further increase in blood pressure in SHR, and by marked limitation of coronary perfusion in normotensive animals, while no changes in heart mechanical function were observed in any of the groups. Postischemic recovery of contractile function, severity of ventricular arrhythmias and lethal injury (infarction size) were worsened in the hypertrophied hearts of C-SHR compared with normotensive C. However, myo-cardial stunning and reperfusion induced ventricular arrhythmias were attenuated by CS in SHR, which was different from deterioration of I/R injury in the hearts of normotensive animals. In contrast, ischemic preconditioning conferred an effective protection against I/R in both groups, although the extent of anti-infarct and anti-arrhythmic effects was lower in SHR. Both forms of stress may improve the altered response to ischemia in hypertensive subjects. In contrast to short-term preconditioning stress, chronic psychosocial stress was associated with a higher risk of lethal arrhythmias and contractile failure in normotensive animals exposed to an acute ischemic challenge. PMID- 22065944 TI - The impact of different sources of body mass index assessment on smoking onset: An application of multiple-source information models. AB - Multiple-source data are often collected to provide better information of some underlying construct that is difficult to measure or likely to be missing. In this article, we describe regression-based methods for analyzing multiple-source data in Stata. We use data from the BROMS Cohort Study, a cohort of Swedish adolescents who collected data on body mass index that was self-reported and that was measured by nurses. We draw together into a single frame of reference both source reports and relate these to smoking onset. This unified method has two advantages over traditional approaches: 1) the relative predictiveness of each source can be assessed and 2) all subjects contribute to the analysis. The methods are applicable to other areas of epidemiology where multiple-source reports are used. PMID- 22065945 TI - Prevalence of chronic obstructive pulmonary disease in rural women of Tamilnadu: implications for refining disease burden assessments attributable to household biomass combustion. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the 13th leading cause of burden of disease worldwide and is expected to become 5th by 2020. Biomass fuel combustion significantly contributes to COPD, although smoking is recognized as the most important risk factor. Rural women in developing countries bear the largest share of this burden resulting from chronic exposures to biomass fuel smoke. Although there is considerable strength of evidence for the association between COPD and biomass smoke exposure, limited information is available on the background prevalence of COPD in these populations. OBJECTIVE: This study was conducted to estimate the prevalence of COPD and its associated factors among non-smoking rural women in Tiruvallur district of Tamilnadu in Southern India. DESIGN: This cross-sectional study was conducted among 900 non smoking women aged above 30 years, from 45 rural villages of Tiruvallur district of Tamilnadu in Southern India in the period between January and May 2007. COPD assessments were done using a combination of clinical examination and spirometry. Logistic regression analysis was performed to examine the association between COPD and use of biomass for cooking. R software was used for statistical analysis. RESULTS: The overall prevalence of COPD in this study was found to be 2.44% (95% CI: 1.43-3.45). COPD prevalence was higher in biomass fuel users than the clean fuel users 2.5 vs. 2%, (OR: 1.24; 95% CI: 0.36-6.64) and it was two times higher (3%) in women who spend >2 hours/day in the kitchen involved in cooking. Use of solid fuel was associated with higher risk for COPD, although no statistically significant results were obtained in this study. CONCLUSION: The estimates generated in this study will contribute significantly to the growing database of available information on COPD prevalence in rural women. Moreover, with concomitant indoor air pollution measurements, it may be possible to increase the resolution of the association between biomass use and COPD prevalence and refine available attributable burden of disease estimates. PMID- 22065946 TI - Concurrent imaging of synaptic vesicle recycling and calcium dynamics. AB - Synaptic transmission involves the calcium dependent release of neurotransmitter from synaptic vesicles. Genetically encoded optical probes emitting different wavelengths of fluorescent light in response to neuronal activity offer a powerful approach to understand the spatial and temporal relationship of calcium dynamics to the release of neurotransmitter in defined neuronal populations. To simultaneously image synaptic vesicle recycling and changes in cytosolic calcium, we developed a red-shifted reporter of vesicle recycling based on a vesicular glutamate transporter, VGLUT1-mOrange2 (VGLUT1-mOr2), and a presynaptically localized green calcium indicator, synaptophysin-GCaMP3 (SyGCaMP3) with a large dynamic range. The fluorescence of VGLUT1-mOr2 is quenched by the low pH of synaptic vesicles. Exocytosis upon electrical stimulation exposes the luminal mOr2 to the neutral extracellular pH and relieves fluorescence quenching. Reacidification of the vesicle upon endocytosis again reduces fluorescence intensity. Changes in fluorescence intensity thus monitor synaptic vesicle exo- and endocytosis, as demonstrated previously for the green VGLUT1-pHluorin. To monitor changes in calcium, we fused the synaptic vesicle protein synaptophysin to the recently improved calcium indicator GCaMP3. SyGCaMP3 is targeted to presynaptic varicosities, and exhibits changes in fluorescence in response to electrical stimulation consistent with changes in calcium concentration. Using real time imaging of both reporters expressed in the same synapses, we determine the time course of changes in VGLUT1 recycling in relation to changes in presynaptic calcium concentration. Inhibition of P/Q- and N-type calcium channels reduces calcium levels, as well as the rate of synaptic vesicle exocytosis and the fraction of vesicles released. PMID- 22065947 TI - Spatiotemporal Molecular Approach of in utero Electroporation to Functionally Decipher Endophenotypes in Neurodevelopmental Disorders. AB - We have only just begun to decipher the complexity of our brain, including its maturation. Correct brain development and communication among brain areas are crucial for proper cognitive behavior. Brain area-specific genes expressed within a particular time window direct neurodevelopmental events such as proliferation, migration, axon guidance, dendritic arborization, and synaptogenesis. These genes can pose as susceptibility factors in neurodevelopmental disorders eventually resulting in area-specific cognitive deficits. Therefore, in utero electroporation (IUE)-mediated gene transfer can aid in creating valuable animal models in which the regionality and time of expression can be restricted for the targeted gene(s). Moreover, through the use of cell-type-specific molecular constructs, expression can be altered in a particular neuronal subset within a distinct area such that we are now able to causally link the function of that gene in that brain region to the etiology of the disorder. Thus, IUE-mediated gene transfer is an attractive molecular technique to spatiotemporally address the developmental aspects of gene function in relation to neurodevelopmental disorder-associated endophenotypes. PMID- 22065948 TI - Beyond cAMP: The Regulation of Akt and GSK3 by Dopamine Receptors. AB - Brain dopamine receptors have been preferred targets for numerous pharmacological compounds developed for the treatment of various neuropsychiatric disorders. Recent discovery that D2 dopamine receptors, in addition to cAMP pathways, can engage also in Akt/GSK3 signaling cascade provided a new framework to understand intracellular signaling mechanisms involved in dopamine-related behaviors and pathologies. Here we review a recent progress in understanding the role of Akt, GSK3, and related signaling molecules in dopamine receptor signaling and functions. Particularly, we focus on the molecular mechanisms involved, interacting partners, role of these signaling events in the action of antipsychotics, psychostimulants, and antidepressants as well as involvement in pathophysiology of schizophrenia, bipolar disorder, and Parkinson's disease. Further understanding of the role of Akt/GSK3 signaling in dopamine receptor functions could provide novel targets for pharmacological interventions in dopamine-related disorders. PMID- 22065949 TI - ROCKing Regeneration: Rho Kinase Inhibition as Molecular Target for Neurorestoration. AB - Regenerative failure in the CNS largely depends on pronounced growth inhibitory signaling and reduced cellular survival after a lesion stimulus. One key mediator of growth inhibitory signaling is Rho-associated kinase (ROCK), which has been shown to modulate growth cone stability by regulation of actin dynamics. Recently, there is accumulating evidence the ROCK also plays a deleterious role for cellular survival. In this manuscript we illustrate that ROCK is involved in a variety of intracellular signaling pathways that comprise far more than those involved in neurite growth inhibition alone. Although ROCK function is currently studied in many different disease contexts, our review focuses on neurorestorative approaches in the CNS, especially in models of neurotrauma. Promising strategies to target ROCK by pharmacological small molecule inhibitors and RNAi approaches are evaluated for their outcome on regenerative growth and cellular protection both in preclinical and in clinical studies. PMID- 22065950 TI - Enhanced Synaptic Activity and Epileptiform Events in the Embryonic KCC2 Deficient Hippocampus. AB - The neuronal potassium-chloride co-transporter 2 [indicated thereafter as KCC2 (for protein) and Kcc2 (for gene)] is thought to play an important role in the post natal excitatory to inhibitory switch of GABA actions in the rodent hippocampus. Here, by studying hippocampi of wild-type (Kcc2(+/+)) and Kcc2 deficient (Kcc2(-/-)) mouse embryos, we unexpectedly found increased spontaneous neuronal network activity at E18.5, a developmental stage when KCC2 is thought not to be functional in the hippocampus. Embryonic Kcc2(-/-) hippocampi have also an augmented synapse density and a higher frequency of spontaneous glutamatergic and GABA-ergic postsynaptic currents than naive age matched neurons. However, intracellular chloride concentration ([Cl(-)](i)) and the reversal potential of GABA-mediated currents (E(GABA)) were similar in embryonic Kcc2(+/+) and Kcc2(-/ ) CA3 neurons. In addition, KCC2 immunolabeling was cytoplasmic in the majority of neurons suggesting that the molecule is not functional as a plasma membrane chloride co-transporter. Collectively, our results show that already at an embryonic stage, KCC2 controls the formation of synapses and, when deleted, the hippocampus has a higher density of GABA-ergic and glutamatergic synapses and generates spontaneous and evoked epileptiform activities. These results may be explained either by a small population of orchestrating neurons in which KCC2 operates early as a chloride exporter or by transporter independent actions of KCC2 that are instrumental in synapse formation and networks construction. PMID- 22065952 TI - How emotions change time. AB - Experimental evidence suggests that emotions can both speed-up and slow-down the internal clock. Speeding up has been observed for to-be-timed emotional stimuli that have the capacity to sustain attention, whereas slowing down has been observed for to-be-timed neutral stimuli that are presented in the context of emotional distractors. These effects have been explained by mechanisms that involve changes in bodily arousal, attention, or sentience. A review of these mechanisms suggests both merits and difficulties in the explanation of the emotion-timing link. Therefore, a hybrid mechanism involving stimulus-specific sentient representations is proposed as a candidate for mediating emotional influences on time. According to this proposal, emotional events enhance sentient representations, which in turn support temporal estimates. Emotional stimuli with a larger share in ones sentience are then perceived as longer than neutral stimuli with a smaller share. PMID- 22065953 TI - Social Defeat during Adolescence and Adulthood Differentially Induce BDNF Regulated Immediate Early Genes. AB - Stressful life events generally enhance the vulnerability for the development of human psychopathologies such as anxiety disorders and depression. The incidence rates of adult mental disorders steeply rises during adolescence in parallel with a structural and functional reorganization of the neural circuitry underlying stress reactivity. However, the mechanisms underlying susceptibility to stress and manifestation of mental disorders during adolescence are little understood. We hypothesized that heightened sensitivity to stress during adolescence reflects age-dependent differences in the expression of activity-dependent genes involved in synaptic plasticity. Therefore, we compared the effect of social stress during adolescence with social stress in adulthood on the expression of a panel of genes linked to induction of long-term potentiation (LTP) and brain-derived neurotrophic factor (BDNF) signaling. We show that social defeat during adolescence and adulthood differentially regulates expression of the immediate early genes BDNF, Arc, Carp, and Tieg1, as measured by qPCR in tissue lysates from prefrontal cortex, nucleus accumbens, and hippocampus. In the hippocampus, mRNA levels for all four genes were robustly elevated following social defeat in adolescence, whereas none were induced by defeat in adulthood. The relationship to coping style was also examined using adult reactive and proactive coping rats. Gene expression levels of reactive and proactive animals were similar in the prefrontal cortex and hippocampus. However, a trend toward a differential expression of BDNF and Arc mRNA in the nucleus accumbens was detected. BDNF mRNA was increased in the nucleus accumbens of proactive defeated animals, whereas the expression level in reactive defeated animals was comparable to control animals. The results demonstrate striking differences in immediate early gene expression in response to social defeat in adolescent and adult rats. PMID- 22065954 TI - The organization of shape and color in vision and art. AB - The aim of this work is to study the phenomenal organization of shape and color in vision and art in terms of microgenesis of the object perception and creation. The idea of "microgenesis" is that the object perception and creation takes time to develop. Our hypothesis is that the roles of shape and color are extracted in sequential order and in the same order these roles are also used by artists to paint objects. Boundary contours are coded before color contours. The microgenesis of the object formation was demonstrated (i) by introducing new conditions derived from the watercolor illusion, where the juxtaposed contours are displaced horizontally or vertically, and based on variations of Matisse's Woman, (ii) by studying descriptions and replications of visual objects in adults and children of different ages, and (iii) by analyzing the linguistic sequence and organization in a free naming task of the attributes related to shape and color. The results supported the idea of the microgenesis of the object perception, namely the temporal order in the formation of the roles of the object properties (shape before color). Some general principles were extracted from the experimental results. They can be a starting point to explore a new domain focused on the microgenesis of shape and color within the more general problem of object organization, where integrated and multidisciplinary studies based on art and vision science can be very useful. PMID- 22065955 TI - External measures of cognition. AB - The human brain is undoubtedly the most impressive, complex, and intricate organ that has evolved over time. It is also probably the least understood, and for that reason, the one that is currently attracting the most attention. In fact, the number of comparative analyses that focus on the evolution of brain size in Homo sapiens and other species has increased dramatically in recent years. In neuroscience, no other issue has generated so much interest and been the topic of so many heated debates as the difference in brain size between socially defined population groups, both its connotations and implications. For over a century, external measures of cognition have been related to intelligence. However, it is still unclear whether these measures actually correspond to cognitive abilities. In summary, this paper must be reviewed with this premise in mind. PMID- 22065951 TI - Anatomical pathways involved in generating and sensing rhythmic whisker movements. AB - The rodent whisker system is widely used as a model system for investigating sensorimotor integration, neural mechanisms of complex cognitive tasks, neural development, and robotics. The whisker pathways to the barrel cortex have received considerable attention. However, many subcortical structures are paramount to the whisker system. They contribute to important processes, like filtering out salient features, integration with other senses, and adaptation of the whisker system to the general behavioral state of the animal. We present here an overview of the brain regions and their connections involved in the whisker system. We do not only describe the anatomy and functional roles of the cerebral cortex, but also those of subcortical structures like the striatum, superior colliculus, cerebellum, pontomedullary reticular formation, zona incerta, and anterior pretectal nucleus as well as those of level setting systems like the cholinergic, histaminergic, serotonergic, and noradrenergic pathways. We conclude by discussing how these brain regions may affect each other and how they together may control the precise timing of whisker movements and coordinate whisker perception. PMID- 22065956 TI - "Pulling telescoped phantoms out of the stump": manipulating the perceived position of phantom limbs using a full-body illusion. AB - Most amputees experience phantom limbs, or the sensation that their amputated limb is still attached to the body. Phantom limbs can be perceived in the location previously occupied by the intact limb, or they can gradually retract inside the stump, a phenomenon referred to as "telescoping". Telescoping is relevant from a clinical point of view, as it tends to be related to increased levels of phantom pain. In the current study we demonstrate how a full-body illusion can be used to temporarily revoke telescoping sensations in upper limb amputees. During this illusion participants view the body of a mannequin from a first person perspective while being subjected to synchronized visuo-tactile stimulation through stroking, which makes them experience the mannequin's body as their own. In Experiment 1 we used an intact mannequin, and showed that amputees can experience ownership of an intact body as well as referral of touch from both hands of the mannequin. In Experiment 2 and 3 we used an amputated mannequin, and demonstrated that depending on the spatial location of the strokes applied to the mannequin, participants experienced their phantom hand to either remain telescoped, or to actually be located below the stump. The effects were supported by subjective data from questionnaires, as well as verbal reports of the perceived location of the phantom hand in a visual judgment task. These findings are of particular interest, as they show that the temporary revoking of telescoping sensations does not necessarily have to involve the visualization of an intact hand or illusory movement of the phantom (as in the rubber hand illusion or mirror visual feedback therapy), but that it can also be obtained through mere referral of touch from the stump to the spatial location corresponding to that previously occupied by the intact hand. Moreover, our study also provides preliminary evidence for the fact that these manipulations can have an effect on phantom pain sensations. PMID- 22065958 TI - Dopamine Modulates Spike Timing-Dependent Plasticity and Action Potential Properties in CA1 Pyramidal Neurons of Acute Rat Hippocampal Slices. AB - Spike timing-dependent plasticity (STDP) is a cellular model of Hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15-20), we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent long-term potentiation (t-LTP) to 171 +/- 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10-20 min) to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the beta-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 +/- 6.9% of ACSF values) in sucrose prepared slices. These results suggest that dopamine signaling is involved in regulating the efficiency to elicit STDP in CA1 pyramidal neurons. PMID- 22065957 TI - Sex differences in the relationship of dietary Fatty acids to cognitive measures in american children. AB - Because the first neurons evolved in an environment high in the n-3 (omega-3) fatty acid docosahexaenoic acid (DHA), this fatty acid became a major component of neural structure and function and makes up 10% of the dry weight of the human brain. Since n-3 fatty acids must come from the diet, this suggests a possible positive role for dietary n-3 fatty acids in cognition and a possible negative role for n-6 fatty acids, which compete with n-3 for access to critical enzymes. Because human females must provide DHA for the growth of the unusually large brains of their offspring from maternal fat stored during childhood, their need for DHA is especially great. We used stepwise regression to determine whether particular dietary fatty acids and other nutrients were related to cognitive performance in over 4000 American children aged 6-16 from the Third National Health and Nutrition Examination Survey; a variety of possible biological, social, and environmental risk factors were statistically controlled. In this context the only dietary factors related to cognitive performance were n-3 and n 6 fatty acids. Dietary n-3 fatty acids were positively related to cognitive test scores in male and female children, while n-6 showed the reverse relationship, significantly so in females. In female children the positive effects of n-3 intake were twice as strong as in males and exceeded the negative effects of lead exposure. This suggests that increasing dietary intake of n-3 and decreasing n-6 fatty acids may have cognitive benefits in children, especially in females. PMID- 22065959 TI - Alpe adria report 2010 - conclusions and recommendations for the treatment of alcohol dependence. PMID- 22065960 TI - How Prevalent is "Food Addiction"? AB - Increasing evidence suggests that binge eating-related disorders could be related to addiction-like eating patterns due to the addictive potential of hyperpalatable foods. Subsequently, important implications have been derived for treatment of those disorders and even political actions. However, studies on the prevalence of food addiction are rare. Few recent studies investigated addictive eating in children, adolescents, and adults. This mini-review presents these first attempts to assess addictive eating and how prevalent addictive eating patterns were in the respective studies. It is concluded that the prevalence of food addiction is increased in obese individuals and even more so in obese patients with binge eating disorder. However, prevalence of food addiction is not sufficient to account for the obesity epidemic. Conversely, an arguably high prevalence of food addiction can also be found in under-, normal-, and overweight individuals. Future studies may investigate which factors are associated with addictive eating in non-obese individuals. PMID- 22065961 TI - A cognitive architecture for the coordination of utterances. AB - Dialog partners coordinate with each other to reach a common goal. The analogy with other joint activities has sparked interesting observations (e.g., about the norms governing turn-taking) and has informed studies of linguistic alignment in dialog. However, the parallels between language and action have not been fully explored, especially with regard to the mechanisms that support moment-by-moment coordination during language use in conversation. We review the literature on joint actions to show (i) what sorts of mechanisms allow coordination and (ii) which types of experimental paradigms can be informative of the nature of such mechanisms. Regarding (i), there is converging evidence that the actions of others can be represented in the same format as one's own actions. Furthermore, the predicted actions of others are taken into account in the planning of one's own actions. Similarly, we propose that interlocutors are able to coordinate their acts of production because they can represent their partner's utterances. They can then use these representations to build predictions, which they take into account when planning self-generated utterances. Regarding (ii), we propose a new methodology to study interactive language. Psycholinguistic tasks that have traditionally been used to study individual language production are distributed across two participants, who either produce two utterances simultaneously or complete each other's utterances. PMID- 22065962 TI - Enhancing the Clinical Potential of AAV Vectors by Capsid Engineering to Evade Pre-Existing Immunity. AB - Vectors based on adeno-associated viruses (AAV) have shown considerable promise in both preclinical models and increasingly in clinical trials. However, one formidable challenge is pre-existing immunity due to widespread exposure to numerous AAV variants and serotypes within the human population, which affect efficacy of clinical trials due to the accompanying high levels of anti-capsid neutralizing antibodies. Transient immunosuppression has promise in mitigating cellular and humoral responses induced by vector application in naive hosts, but cannot overcome the problem that pre-existing neutralizing antibodies pose toward the goal of safe and efficient gene delivery. Shielding of AAV from antibodies, however, may be possible by covalent attachment of polymers to the viral capsid or by encapsulation of vectors inside biomaterials. In addition, there has been considerable progress in using rational mutagenesis, combinatorial libraries, and directed evolution approaches to engineer capsid variants that are not recognized by anti-AAV antibodies generally present in the human population. While additional progress must be made, such strategies, alone or in combination with immunosuppression to avoid de novo induction of antibodies, have strong potential to significantly enhance the clinical efficacy of AAV vectors. PMID- 22065963 TI - An alternative path for the evolution of biological nitrogen fixation. AB - Nitrogenase catalyzed nitrogen fixation is the process by which life converts dinitrogen gas into fixed nitrogen in the form of bioavailable ammonia. The most common form of nitrogenase today requires a complex metal cluster containing molybdenum (Mo), although alternative forms exist which contain vanadium (V) or only iron (Fe). It has been suggested that Mo-independent forms of nitrogenase (V and Fe) were responsible for N(2) fixation on early Earth because oceans were Mo depleted and Fe-rich. Phylogenetic- and structure-based examinations of multiple nitrogenase proteins suggest that such an evolutionary path is unlikely. Rather, our results indicate an evolutionary path whereby Mo-dependent nitrogenase emerged within the methanogenic archaea and then gave rise to the alternative forms suggesting that they arose later, perhaps in response to local Mo limitation. Structural inferences of nitrogenase proteins and related paralogs suggest that the ancestor of all nitrogenases had an open cavity capable of binding metal clusters which conferred reactivity. The evolution of the nitrogenase ancestor and its associated bound metal cluster was controlled by the availability of fixed nitrogen in combination with local environmental factors that influenced metal availability until a point in Earth's geologic history where the most desirable metal, Mo, became sufficiently bioavailable to bring about and refine the solution (Mo-nitrogenase) we see perpetuated in extant biology. PMID- 22065964 TI - Immune Responses to rAAV6: The Influence of Canine Parvovirus Vaccination and Neonatal Administration of Viral Vector. AB - Recombinant adeno-associated viral (rAAV) vectors promote long-term gene transfer in many animal species. Significant effort has focused on the evaluation of rAAV delivery and the immune response in both murine and canine models of neuromuscular disease. However, canines provided for research purposes are routinely vaccinated against canine parvovirus (CPV). rAAV and CPV possess significant homology and are both parvoviruses. Thus, any immune response generated to CPV vaccination has the potential to cross-react with rAAV vectors. In this study, we investigated the immune response to rAAV6 delivery in a cohort of CPV-vaccinated canines and evaluated multiple vaccination regimens in a mouse model of CPV-vaccination. We show that CPV-vaccination stimulates production of neutralizing antibodies with minimal cross-reactivity to rAAV6. In addition, no significant differences were observed in the magnitude of the rAAV6-directed immune response between CPV-vaccinated animals and controls. Moreover, CPV vaccination did not inhibit rAAV6-mediated transduction. We also evaluated the immune response to early rAAV6-vaccination in neonatal mice. The influence of maternal hormones and cytokines leads to a relatively permissive state in the neonate. We hypothesized that immaturity of the immune system would permit induction of tolerance to rAAV6 when delivered during the neonatal period. Mice were vaccinated with rAAV6 at 1 or 5 days of age, and subsequently challenged with rAAV6 exposure during adulthood via two sequential IM injections, 1 month apart. All vaccinated animals generated a significant neutralizing antibody response to rAAV6-vaccination that was enhanced following IM injection in adulthood. Taken together, these data demonstrate that the immune response raised against rAAV6 is distinct from that which is elicited by the standard parvoviral vaccines and is sufficient to prevent stable tolerization in neonatal mice. PMID- 22065965 TI - Low-grade lymphoma: Beyond fludarabine-single therapy. PMID- 22065966 TI - Engineered therapeutic antibodies with enhanced effector functions: Clinical application of the Potelligent(r) Technology. PMID- 22065967 TI - Fortuitous detection of esophageal pneumatosis in a neutropenic patient. PMID- 22065968 TI - Plasma cell leukemia with rouleaux formation involving neoplastic cells and RBC. PMID- 22065969 TI - Treatment of chronic graft-versus-host disease: Past, present and future. AB - Chronic GVHD was recognized as a complication of allogeneic hematopoietic cell transplantation more than 30 years ago, but progress has been slowed by the limited insight into the pathogenesis of the disease and the mechanisms that lead to development of immunological tolerance. Only 6 randomized phase III treatment studies have been reported. Results of retrospective studies and prospective phase II clinical trials suggested overall benefit from treatment with mycophenolate mofetil or thalidomide, but these results were not substantiated by phase III studies of initial systemic treatment for chronic GVHD. A comprehensive review of published reports showed numerous deficiencies in studies of secondary treatment for chronic GVHD. Fewer than 10% of reports documented an effort to minimize patient selection bias, used a consistent treatment regimen, or tested a formal statistical hypothesis that was based on a contemporaneous or historical benchmark. In order to enable valid comparison of the results from different studies, eligibility criteria, definitions of individual organ and overall response, and time of assessment should be standardized. Improved treatments are more likely to emerge if reviewers and journal editors hold authors to higher standards in evaluating manuscripts for publication. PMID- 22065970 TI - ABO-incompatible renal transplantation: From saline flushes to antigen-specific immunoadsorption-Tools to overcome the barrier. AB - On April 23, 1951, a 30-year-old woman received the first intentional ABOi (ABO incompatible) renal transplantation in Boston. At that time, it was commonly believed that intensely rinsing the graft to remove blood would be sufficient to overcome any immunological problems associated with blood type incompatibility. However, when the abovementioned patient and another ABOi transplant recipient died within a month, Humes and colleagues arrived at the same conclusion: "We do not feel that renal transplantation in the presence of blood incompatibility is wise." In the decades that followed, we learned that the oligosaccharide surface antigens representing the ABO-blood group antigens are expressed not only on erythrocytes but also on cells from various tissues, including the vascular endothelium. The growing gap between organ demand and availability has sparked efforts to overcome the ABO barrier. After its disappointing results in the early 1970s, Japan became the leader of this endeavor in the 1980s. All protocols are based on 2 strategies: removal of preformed antibodies with extracorporeal techniques and inhibition of ongoing antibody production. Successful ABOi renal transplantation became possible with the advent of splenectomy, new immunosuppressive drugs (e.g., rituximab, a monoclonal antibody against CD20), and extracorporeal methods such as antigen-specific immunoadsorption. This review summarizes the underlying pathophysiology of ABOi transplantation and the different protocols available. Further, we briefly touch potential short- and long-term problems, particularly the incidence of infectious complications and malignancies, that can arise with high-intensity immunosuppressive therapy. PMID- 22065971 TI - Recent advances in the path toward the cure for chronic myeloid leukemia. AB - Through the phase 3 International Randomized Study of Interferon vs. STI571 (IRIS) trial, imatinib emerged as the standard treatment for chronic myeloid leukemia (CML) and has successfully prolonged the duration of both the chronic phase (CP) and the disease-free state. The majority of newly diagnosed patients treated for CP-CML achieve a complete cytogenetic response (CCyR), and over time, most of these eventually achieve major molecular responses (MMRs) and even complete molecular responses (CMRs). In ongoing phase 3 randomized trials of second-generation tyrosine kinase inhibitors (TKIs), nilotinib and dasatinib have been found to have superior efficacies in helping achieve cytogenetic and molecular responses, including MMRs and CMRs. However, only the MMR rate was significantly higher in bosutinib compared with the imatinib control, but not in CCyR rate. Current reports of imatinib discontinuation suggested that achieving CMR is an important prerequisite for CML to be cured. Recent data from the STIM (Stop Imatinib) trial showed that imatinib can be successfully discontinued in patients who achieve a certain level of CMR. Standardized real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) assays have been available in routine clinical practice, and efforts are being focused on achieving higher sensitivity and optimizing the time of imatinib discontinuation. Although very few patients are cured by administration of only Bcr-Abl TKIs, including imatinib and second-generation TKIs, current advances may eventually make this possible. This report summarizes the detailed clinical data obtained in the DASISION, ENESTnd, and BELA studies and discusses high-sensitivity detection methods and future therapeutic strategies. PMID- 22065972 TI - Clinical significance of B cell-activating factor (BAFF) and a proliferation inducing ligand (APRIL) in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. AB - BACKGROUND: BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) are members of the tumor necrosis factor family and promote B cell survival and proliferation. We evaluated the correlation between serum concentration of BAFF or APRIL and severity of acute graft-versus-host disease (GVHD). METHODS: Fifteen patients who received allogeneic hematopoietic stem transplantation for leukemia and developed acute GVHD were enrolled. We determined serum concentrations of BAFF and APRIL at the onset of the first clinical manifestation of GVHD by enzyme-linked immunosorbent assay. RESULTS: Nine patients had grade 2 acute GVHD, and 6 had grade 3-4 acute GVHD. The BAFF serum concentration was higher in patients with grade 3-4 acute GVHD (1,093.42 in grade 2 vs. 2,171.99 pg/mL in grade 3-4), although the difference was not significant (P=0.077). However, the ratio of BAFF serum concentration to absolute lymphocyte count (ALC) (BAFF/ALC) was significantly higher in patients with grade 3-4 acute GVHD (P=0.045). The APRIL serum concentration and APRIL/ALC ratio showed similar results (P=0.077 and P=0.013, respectively). CONCLUSION: Patients with grade 3-4 acute GVHD had higher BAFF/ALC and APRIL/ALC ratios than patients with grade 2 acute GVHD. These findings suggest that B cells might play an important role in the development of acute GVHD, and that the BAFF and APRIL concentrations in serum might be significant predictive factors for estimating the severity of acute GVHD. Their clinical significance should be further evaluated in a larger patient population. PMID- 22065973 TI - Fludarabine-containing chemotherapy for patients with previously untreated low grade non-Hodgkin's lymphoma. AB - BACKGROUND: The clinical efficacy and safety of fludarabine combination chemotherapy was investigated for the treatment of previously untreated patients with low-grade (NHL). METHODS: Twenty-five patients who were newly diagnosed as low-grade NHL were treated with fludarabine combination chemotherapy. Fludarabine combination regimens consisted of fludarabine, mitoxantrone and dexamethasone or fludarabine, cyclophosphamide and mitoxantrone with or without rituximab and repeated every 4 weeks. RESULTS: The median age was 60 years (range, 35-77 years), with 13 of 25 patients (52%) >=60 years of age. Seven of 25 patients (28%) with an intermediate risk follicular lymphoma international prognostic index (FLIPI) and 9 of 25 patients (36%) with a high risk FLIPI were enrolled in this study. The delivered median number of chemotherapy was six (range, 2-9 cycles). The overall response rate with fludarabine-based treatment was 88%, including 52% complete remission and 36% partial remission. During the median follow-up of 19 months, the estimated 2-year event-free survival was 63+/-10% (95% CI, 43-83) and the 2-year overall survival was 78+/-9% (95% CI, 60-96). Fludarabine combination chemotherapy was frequently associated with grade 3 or 4 neutropenia in 84% patients. However, neutropenic infection was observed in only one (4%) patient. Four patients (16%) showed grade 3 or more non-hematologic toxicities, such as acute coronary syndrome, intracranial hemorrhage, anaphylaxis and gastric cancer. CONCLUSION: Fludarabine-combination treatment was a highly active regimen with well toleration in untreated low-grade NHL. PMID- 22065974 TI - New clinical score for disease activity at diagnosis in Langerhans cell histiocytosis. AB - BACKGROUND: The clinical presentation and course of Langerhans cell histiocytosis (LCH) are variable, ranging from an isolated, spontaneously remitting bone lesion to multisystem disease with risk organ involvement. Treatment of LCH ranges from a wait-and-see attitude to intensive multidrug therapy and, in some cases, bone marrow transplantation. It is necessary to develop an objective score for assessing disease activity in patients with LCH. We propose a new clinical scoring system to evaluate disease activity at diagnosis that can predict the clinical outcomes of LCH and correlate it with clinical courses. METHODS: Clinical data, obtained from children diagnosed with LCH at Asan Medical Center and Hanyang University Hospital between March 1998 and February 2009, were studied retrospectively. The scoring system was developed according to the basic biological data, radiological findings, and physical findings and applied to a database containing information on 133 patients. RESULTS: The median age of the 133 patients (74 male, 59 female) was 52 months (range, 0.6-178 months), and LCH was diagnosed based on CD1a positivity. At diagnosis, the score distributions were highly asymmetrical: the score was between 1 and 2 in 75.9% of cases, 3-6 in 15.8%, and greater than 6 in 8.3%. Initial scores above 6 were highly predictive of reactivation and late complications. CONCLUSION: This new LCH disease activity score provides an objective tool for assessing disease severity, both at diagnosis and during follow-up. PMID- 22065975 TI - Genotypic influence of alpha-deletions on the phenotype of Indian sickle cell anemia patients. AB - BACKGROUND: Some reports have shown that co-inheritance of alpha-thalassemia and sickle cell disease improves hematological parameters and results in a relatively mild clinical picture for patients; however, the exact molecular basis and clinical significance of the interaction between alpha-thalassemia and sickle cell disease in India has not yet been described. There is little agreement on the clinical effects of alpha-thalassemia on the phenotype of sickle cell disease. METHODS: Complete blood count and red cell indices were measured by an automated cell analyzer. Quantitative assessment of hemoglobin variants HbF, HbA, HbA(2), and HbS was performed by high performance liquid chromatography (HPLC). DNA extraction was performed using the phenol-chloroform method, and molecular study for common alpha-deletions was done by gap-PCR. RESULTS: Out of 60 sickle cell anemia patients, the alpha-thalassemia genotype was found in 18 patients. Three patients had the triplicated alpha-genotype (Anti alpha-3.7 kb), and the remaining patients did not have alpha-deletions. This study indicates that patients with co-existing alpha-thalassemia and sickle cell disease had a mild phenotype, significantly improved hematological parameters, and fewer blood transfusions than the patients with sickle cell anemia without co-existing alpha deletions. CONCLUSION: Co-existence of alpha-thalassemia and sickle cell anemia has significant effects on the phenotype of Indian sickle cell patients. PMID- 22065976 TI - The prevalence of anemia and iron depletion in the population aged 10 years or older. AB - BACKGROUND: Anemia and iron depletion continue to be common disorders in the world. This study was aimed at assessing the prevalence of anemia and iron depletion in apparently healthy Koreans aged 10 years or more. METHODS: We used the data of the 4(th) Korean National Health & Nutrition Examination Survey (KNHANES), which assessed 7,607 individuals (3,337 males and 4,270 females). Iron depletion was defined as serum ferritin less than 15 ng/mL. RESULTS: In males, mean hemoglobin (Hb) concentration decreased after the age of 50. The prevalence of anemia was 7.1% in 60 to 69 year olds and 12.3% in men aged 70 or older. As for females, the prevalence of anemia was 8.8% in 15 to 17 year olds, 16.7% in 18 to 49 year olds, 10.9% in 60 to 69 year olds, and 18.2% women aged 70 or older. In males, the prevalence of iron depletion was 8.6% at ages 10 to 14 years, 3.9% at 15 to 17, and 2.6% at 70 years or older. In females, the prevalence of iron depletion was 17.2% at ages 10 to 14 years, 24.1% at 15 to 17, 33.0% at 18 to 49, and 5.7% at 70 years or older. Although normocytic anemia was most common in both males and females, the proportion of microcytosis and macrocytosis increased at age 70 or older. CONCLUSION: The prevalence of anemia and iron depletion was high in women of reproductive age and in the elderly. Considering the rapid increase in the older population, an intervention to prevent anemia and iron depletion is imperative. PMID- 22065977 TI - Clinical significance of anti-mitochondrial antibodies in a patient with chronic graft-versus-host disease following hematopoietic stem cell transplantation. AB - Recent studies indicate that patients with chronic graft-versus-host disease (GVHD) are not expected to show positivity for anti-mitochondrial antibody (AMA), which is a specific disease marker for primary biliary cirrhosis (PBC). A differential diagnosis between PBC and hepatic involvement of GVHD based on clinical manifestations and pathologic study is difficult because both diseases show similar results. Therefore, the presence of AMA may be important for distinguishing each disease. Here, we report a case of hepatic involvement of chronic GVHD with positive AMA, in which the pathologic findings and initial presentation of clinical findings were compatible with both PBC and chronic GVHD. PMID- 22065978 TI - A case of follicular B-cell lymphoma treated using clarithromycin. AB - We report a case of follicular B-cell lymphoma (FL) treated successfully using clarithromycin (CAM). A 44-year-old man who presented with lymphadenopathy was diagnosed with FL after a histological examination of his biopsy specimens. He was administered chemotherapy with R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone) following which stable disease was achieved. However, the subsequent clinical course showed partial remission of FL and stable disease with tumor regrowth, each of which was treated with chemotherapeutic regimens. Since the patient was diagnosed with leukocytopenia, he could not undergo chemotherapy for the third regrowth; hence, he was administered CAM. His lymphadenopathy regressed and the levels of soluble interleukin 2-receptor decreased. This case shows that treatment using CAM may be effective in some cases of FL. PMID- 22065979 TI - A controversial conclusion regarding primary extranodal diffuse large B-cell lymphoma. PMID- 22065980 TI - Acceptance and expectance: Cultural norms for alcohol use in Denmark. AB - Alcohol consumption levels in Denmark are high with the risk of increased morbidity and mortality in the population. It is suggested that people's views of "normal" use of alcohol must be the platform for formulating effective alcohol education and prevention strategies. However, little is known about the cultural norms for alcohol use. The aim of this article is to examine the perceptions of cultural norms for alcohol use in Denmark among different age groups and the similarities and differences between the groups, including examining how people construct and negotiate the cultural norms for drinking. Five focus group interviews were conducted with one group per the following age groups: 16-20; 21 34; 35-44; 45-64; and 65-82. These groups consisted of both men and women with five to six participants in each group (a total of 27). Thematic analysis was performed with the aim of developing themes that reflected the cultural norms for alcohol use. The unifying theme of this research was Danish people's acceptance and expectance of social drinking. Alcohol is widely accepted and associated with mutual expectations to drink, leading to identification of cultural influences and facilitation to drink. The social drinking context plays an important role in people's perceptions of the normality of drinking. This includes the selection of particular beverages, and regularly leads to consumption above the recommended levels for low risk to health. This calls for public health attention that promotes low risk drinking in the social context and aims to prevent and reduce serious alcohol-related harm and health problems across the population. PMID- 22065981 TI - Social injury: An interpretative phenomenological analysis of the attitudes towards suicide of lay persons in Ghana. AB - One way of furthering our understanding of suicidal behaviour is to examine people's attitudes towards it and how they conceive the act. The aim of this study was to understand how lay persons conceive the impact of suicide on others and how that influences their attitudes towards suicide; and discuss the implications for suicide prevention in Ghana. This is a qualitative study, using a semi-structured interview guide to investigate the attitudes and views of 27 lay persons from urban and rural settings in Ghana. Interpretative Phenomenological Analysis was used to analyse the data. Findings showed that the perceived breach of interrelatedness between people due to suicidal behaviour influenced the informants' view of suicide as representing a social injury. Such view of suicide influenced the negative attitudes the informants expressed towards the act. The negative attitudes towards suicide in Ghana are cast in consequential terms. Thus, suicide is an immoral act because it socially affects others negatively. The sense of community within the African ethos and The Moral Causal Ontology for Suffering are theoretical postulations that are used to offer some explanations of the findings in this study. PMID- 22065982 TI - Gout, genetics and ABC transporters. AB - Gout is a chronic arthritic disease associated with high levels of urate in blood. Recent advances in research have permitted the identification of several new and common genetic factors underlying the disease. Among them, a polymorphism in the ABC transporter gene ATP-binding cassette transporter isoform G2 has been highlighted. ATP-binding cassette transporter isoform G2 was found to be involved in renal urate elimination, and the presence of the Q141K polymorphism to induce a 2-fold decrease in urate efflux. The Q141K variant has been shown to have impaired trafficking, leading to its intracellular retention, whereas the wild type protein is expressed on the cell surface. Several agents are being studied for the purpose of improving folding, trafficking and function of various ABC transporters, including ATP-binding cassette transporter isoform G2. If successful, this strategy opens doors to potential new therapies for gout. PMID- 22065983 TI - Acute spontaneous spinal subdural haematoma presenting as paraplegia and complete recovery with non-operative treatment. AB - Spontaneous spinal subdural haematoma (SSDH) with no underlying pathology is a very rare condition. Only 20 cases have been previously reported. It can be caused by abnormalities of coagulation, blood dyscrasia, or trauma, underlying neoplasm, and arteriovenous malformation. It occurs most commonly in the thoracic spine and presents with sudden back pain radiating to the arms, legs or trunk, and varying degrees of motor, sensory, and autonomic disturbances. Although the main approach to management is surgical decompression, conservative management is used as well. We report the case of a 57-year-old man who presented with sudden severe low back pain followed by rapid onset of complete paraplegia. Magnetic resonance imaging (MRI) revealed an anterior subdural haematoma from T9 to L1 with cord compression. Corticosteroid treatment was administered. The patient showed substantial clinical improvement after 7 days of bed rest and an intense rehabilitation programme. An MRI scan and a computed tomography angiogram did not reveal any underlying pathology to account for the subdural haematoma. PMID- 22065984 TI - Antigenic, immunologic and genetic characterization of rough strains B. abortus RB51, B. melitensis B115 and B. melitensis B18. AB - The lipopolysaccharide (LPS) is considered the major virulent factor in Brucella spp. Several genes have been identified involved in the synthesis of the three LPS components: lipid A, core and O-PS. Usually, Brucella strains devoid of O-PS (rough mutants) are less virulent than the wild type and do not induce undesirable interfering antibodies. Such of them proved to be protective against brucellosis in mice. Because of these favorable features, rough strains have been considered potential brucellosis vaccines. In this study, we evaluated the antigenic, immunologic and genetic characteristics of rough strains B. abortus RB51, B. melitensis B115 and B. melitensis B18. RB51 derived from B. abortus 2308 virulent strain and B115 is a natural rough strain in which the O-PS is present in the cytoplasm. B18 is a rough rifampin-resistan mutant isolated in our laboratory. The surface antigenicity of RB51, B115 and B18 was evaluated by testing their ability to bind antibodies induced by rough or smooth Brucella strains. The antibody response induced by each strain was evaluated in rabbits. Twenty-one genes, involved in the LPS-synthesis, were sequenced and compared with the B. melitensis 16M strain. The results indicated that RB51, B115 and B18 have differences in antigenicity, immunologic and genetic properties. Particularly, in B115 a nonsense mutation was detected in wzm gene, which could explain the intracellular localization of O-PS in this strain. Complementation studies to evaluate the precise role of each mutation in affecting Brucella morphology and its virulence, could provide useful information for the assessment of new, attenuated vaccines for brucellosis. PMID- 22065985 TI - Estimation of recurrence of colorectal adenomas with dependent censoring using weighted logistic regression. AB - In colorectal polyp prevention trials, estimation of the rate of recurrence of adenomas at the end of the trial may be complicated by dependent censoring, that is, time to follow-up colonoscopy and dropout may be dependent on time to recurrence. Assuming that the auxiliary variables capture the dependence between recurrence and censoring times, we propose to fit two working models with the auxiliary variables as covariates to define risk groups and then extend an existing weighted logistic regression method for independent censoring to each risk group to accommodate potential dependent censoring. In a simulation study, we show that the proposed method results in both a gain in efficiency and reduction in bias for estimating the recurrence rate. We illustrate the methodology by analyzing a recurrent adenoma dataset from a colorectal polyp prevention trial. PMID- 22065986 TI - Flavaglines alleviate doxorubicin cardiotoxicity: implication of Hsp27. AB - BACKGROUND: Despite its effectiveness in the treatment of various cancers, the use of doxorubicin is limited by a potentially fatal cardiomyopathy. Prevention of this cardiotoxicity remains a critical issue in clinical oncology. We hypothesized that flavaglines, a family of natural compounds that display potent neuroprotective effects, may also alleviate doxorubicin-induced cardiotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Our in vitro data established that a pretreatment with flavaglines significantly increased viability of doxorubicin-injured H9c2 cardiomyocytes as demonstrated by annexin V, TUNEL and active caspase-3 assays. We demonstrated also that phosphorylation of the small heat shock protein Hsp27 is involved in the mechanism by which flavaglines display their cardioprotective effect. Furthermore, knocking-down Hsp27 in H9c2 cardiomyocytes completely reversed this cardioprotection. Administration of our lead compound (FL3) to mice attenuated cardiomyocyte apoptosis and cardiac fibrosis, as reflected by a 50% decrease of mortality. CONCLUSIONS/SIGNIFICANCE: These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induced cardiac toxicity. PMID- 22065987 TI - Comparison of intravenous medetomidine and medetomidine/ketamine for immobilization of free-ranging variable flying foxes (Pteropus hypomelanus). AB - Medetomidine (0.03 mg/kg) and medetomidine/ketamine (0.05/5.0 and 0.025/2.5 mg/kg), administered by intravenous injection, were evaluated for short-term immobilization of wild-caught variable flying foxes (Pteropus hypomelanus). Medetomidine alone produced incomplete chemical restraint and a stressful, prolonged induction. Both ketamine/medetomidine doses produced a smooth induction and complete immobilization. The combined medetomidine/ketamine dose of 0.025/2.5 mg/kg produced a rapid induction (232+/-224 sec) with minimal struggling and vocalization, a complete and effective immobilization period, and tended to lead to a faster and better quality recovery than medetomidine alone or a higher dose of medetomidine and ketamine (0.05/5.0 mg/kg), thus reducing holding time and permitting an earlier release of the bat back into the wild. PMID- 22065988 TI - Characterization of the GDP-D-mannose biosynthesis pathway in Coxiella burnetii: the initial steps for GDP-beta-D-virenose biosynthesis. AB - Coxiella burnetii, the etiologic agent of human Q fever, is a gram-negative and naturally obligate intracellular bacterium. The O-specific polysaccharide chain (O-PS) of the lipopolysaccharide (LPS) of C. burnetii is considered a heteropolymer of the two unusual sugars beta-D-virenose and dihydrohydroxystreptose and mannose. We hypothesize that GDP-D-mannose is a metabolic intermediate to GDP-beta-D-virenose. GDP-D-mannose is synthesized from fructose-6-phosphate in 3 successive reactions; Isomerization to mannose-6 phosphate catalyzed by a phosphomannose isomerase (PMI), followed by conversion to mannose-1-phosphate mediated by a phosphomannomutase (PMM) and addition of GDP by a GDP-mannose pyrophosphorylase (GMP). GDP-D-mannose is then likely converted to GDP-6-deoxy-D-lyxo-hex-4-ulopyranose (GDP-Sug), a virenose intermediate, by a GDP-mannose-4,6-dehydratase (GMD). To test the validity of this pathway in C. burnetii, three open reading frames (CBU0671, CBU0294 and CBU0689) annotated as bifunctional type II PMI, as PMM or GMD were functionally characterized by complementation of corresponding E. coli mutant strains and in enzymatic assays. CBU0671, failed to complement an Escherichia coli manA (PMM) mutant strain. However, complementation of an E. coli manC (GMP) mutant strain restored capsular polysaccharide biosynthesis. CBU0294 complemented a Pseudomonas aeruginosa algC (GMP) mutant strain and showed phosphoglucomutase activity (PGM) in a pgm E. coli mutant strain. Despite the inability to complement a manA mutant, recombinant C. burnetii PMI protein showed PMM enzymatic activity in biochemical assays. CBU0689 showed dehydratase activity and determined kinetic parameters were consistent with previously reported data from other organisms. These results show the biological function of three C. burnetii LPS biosynthesis enzymes required for the formation of GDP-D-mannose and GDP-Sug. A fundamental understanding of C. burnetii genes that encode PMI, PMM and GMP is critical to fully understand the biosynthesic pathway of GDP-beta-D-virenose and LPS structure in C. burnetii. PMID- 22065989 TI - Environmental factors controlling the distribution of symbiodinium harboured by the coral Acropora millepora on the Great Barrier Reef. AB - BACKGROUND: The Symbiodinium community associated with scleractinian corals is widely considered to be shaped by seawater temperature, as the coral's upper temperature tolerance is largely contingent on the Symbiodinium types harboured. Few studies have challenged this paradigm as knowledge of other environmental drivers on the distribution of Symbiodinium is limited. Here, we examine the influence of a range of environmental variables on the distribution of Symbiodinium associated with Acropora millepora collected from 47 coral reefs spanning 1,400 km on the Great Barrier Reef (GBR), Australia. METHODOLOGY/PRINCIPAL FINDINGS: The environmental data included Moderate Resolution Imaging Spectroradiometer (MODIS) satellite data at 1 km spatial resolution from which a number of sea surface temperature (SST) and water quality metrics were derived. In addition, the carbonate and mud composition of sediments were incorporated into the analysis along with in situ water quality samples for a subset of locations. Analyses were conducted at three spatio-temporal scales [GBR (regional-scale), Whitsunday Islands (local-scale) and Keppel Islands/Trunk Reef (temporal)] to examine the effects of scale on the distribution patterns. While SST metrics were important drivers of the distribution of Symbiodinium types at regional and temporal scales, our results demonstrate that spatial variability in water quality correlates significantly with Symbiodinium distribution at local scales. Background levels of Symbiodinium types were greatest at turbid inshore locations of the Whitsunday Islands where SST predictors were not as important. This was not the case at regional scales where combinations of mud and carbonate sediment content coupled with SST anomalies and mean summer SST explained 51.3% of the variation in dominant Symbiodinium communities. CONCLUSIONS/SIGNIFICANCE: Reef corals may respond to global-scale stressors such as climate change through changes in their resident symbiont communities, however, management of local-scale stressors such as altered water quality is also necessary for maintenance of coral-Symbiodinium associations. PMID- 22065990 TI - Reducing crowding by weakening inhibitory lateral interactions in the periphery with perceptual learning. AB - We investigated whether lateral masking in the near-periphery, due to inhibitory lateral interactions at an early level of central visual processing, could be weakened by perceptual learning and whether learning transferred to an untrained, higher-level lateral masking known as crowding. The trained task was contrast detection of a Gabor target presented in the near periphery (4 degrees ) in the presence of co-oriented and co-aligned high contrast Gabor flankers, which featured different target-to-flankers separations along the vertical axis that varied from 2lambda to 8lambda. We found both suppressive and facilitatory lateral interactions at target-to-flankers distances (2lambda - 4lambda and 8lambda, respectively) that were larger than those found in the fovea. Training reduces suppression but does not increase facilitation. Most importantly, we found that learning reduces crowding and improves contrast sensitivity, but has no effect on visual acuity (VA). These results suggest a different pattern of connectivity in the periphery with respect to the fovea as well as a different modulation of this connectivity via perceptual learning that not only reduces low level lateral masking but also reduces crowding. These results have important implications for the rehabilitation of low-vision patients who must use peripheral vision to perform tasks, such as reading and refined figure-ground segmentation, which normal sighted subjects perform in the fovea. PMID- 22065991 TI - Batf3-dependent CD11b(low/-) peripheral dendritic cells are GM-CSF-independent and are not required for Th cell priming after subcutaneous immunization. AB - Dendritic cells (DCs) subsets differ in precursor cell of origin, functional properties, requirements for growth factors, and dependence on transcription factors. Lymphoid-tissue resident CD8alpha(+) conventional DCs (cDCs) and CD11b(low/-)CD103(+) non-lymphoid DCs are developmentally related, each being dependent on FMS-like tyrosine kinase 3 ligand (Flt3L), and requiring the transcription factors Batf3, Irf8, and Id2 for development. It was recently suggested that granulocyte/macrophage colony stimulating factor (GM-CSF) was required for the development of dermal CD11b(low/-)Langerin(+)CD103(+) DCs, and that this dermal DC subset was required for priming autoreactive T cells in experimental autoimmune encephalitis (EAE). Here, we compared development of peripheral tissue DCs and susceptibility to EAE in GM-CSF receptor deficient (Csf2rb(-/-)) and Batf3(-/-) mice. We find that Batf3-dependent dermal CD11b(low/ )Langerin(+) DCs do develop in Csf2rb(-/-) mice, but that they express reduced, but not absent, levels of CD103. Further, Batf3(-/-) mice lacking all peripheral CD11b(low/-) DCs show robust Th cell priming after subcutaneous immunization and are susceptible to EAE. Our results suggest that defective T effector priming and resistance to EAE exhibited by Csf2rb(-/-) mice does not result from the absence of dermal CD11b(low/-)Langerin(+)CD103(+) DCs. PMID- 22065992 TI - Fossil plotopterid seabirds from the Eo-Oligocene of the Olympic Peninsula (Washington State, USA): descriptions and functional morphology. AB - The plotopterids (Aves, Plotopteridae) were a group of extinct wing-propelled marine birds that are known from Paleogene-aged sediments (Eocene to Miocene), mostly around the Pacific Rim (especially Japan and the northwest coast of North America). While these birds exhibit a strikingly similar wing morphology to penguins (Spheniscidae), they also share derived characters with pelecaniform birds that are absent in penguins and exhibit apparently superficial similarities with auks (Alcidae: Charadriiformes). Despite quite an abundant fossil record, these birds have been little studied, and in particular their functional morphology remains little understood. Here we present osteological overviews of specimens from the northwest coast of Washington state (USA). We give an amended diagnosis for the well-represented North American genus, Tonsala Olson, 1980, describe a new large species, and examine the functional morphology of plotopterids showing that the ratio of humeral strength to femoral strength is quite low in one well-represented species Tonsala buchanani sp.nov., relative to both extant penguins and alcids. While the femoral strength of Tonsala buchanani is 'penguin-grade', its humeral strength is more 'alcid-grade'. These results have implications for understanding the mode-of-locomotion of these extinct marine birds. Although not related to Spheniscidae, our descriptions and functional results suggest that Tonsala buchanani sustained similar loads in walking, but slightly lower humeral loads during swimming, than a modern penguin. This suggests a swimming mode that is more similar to living alcids, than to the highly-specialised locomotor strategy of living and fossil penguins. PMID- 22065993 TI - CCND1 as a predictive biomarker of neoadjuvant chemotherapy in patients with locally advanced head and neck squamous cell carcinoma. AB - BACKGROUND: Cyclin D1 (CCND1) has been associated with chemotherapy resistance and poor prognosis. In this study, we tested the hypothesis that CCND1 expression determines response and clinical outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) patients treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. METHODOLOGY AND FINDINGS: 224 patients with HNSCC were treated with either cisplatin-based chemotherapy followed by surgery and radiotherapy (neoadjuvant group, n = 100) or surgery and radiotherapy (non neoadjuvant group, n = 124). CCND1 expression was assessed by immunohistochemistry. CCND1 levels were analyzed with chemotherapy response, disease-free survival (DFS) and overall survival (OS). There was no significant difference between the neoadjuvant group and non-neoadjuvant group in DFS and OS (p = 0.929 and p = 0.760) when patients treated with the indiscriminate administration of cisplatin-based chemotherapy. However, in the neoadjuvant group, patients whose tumors showed a low CCND1 expression more likely respond to chemotherapy (p<0.001) and had a significantly better OS and DFS than those whose tumors showed a high CCND1 expression (73% vs 8%, p<0.001; 63% vs 6%, p<0.001). Importantly, patients with a low CCND1 expression in neoadjuvant group received more survival benefits than those in non-neoadjuvant group (p = 0.016), however patients with a high CCND1 expression and treated with neoadjuvant chemotherapy had a significantly poor OS compared to those treated with surgery and radiotherapy (p = 0.032). A multivariate survival analysis also showed CCND1 expression was an independent predictive factor (p<0.001). CONCLUSIONS: This study suggests that some but not all patients with HNSCC may benefit from neoadjuvant chemotherapy with cisplatin-based regimen and CCND1 expression may serve as a predictive biomarker in selecting patients undergo less than two cycles of neoadjuvant chemotherapy. PMID- 22065994 TI - Differential gene expression at coral settlement and metamorphosis--a subtractive hybridization study. AB - BACKGROUND: A successful metamorphosis from a planktonic larva to a settled polyp, which under favorable conditions will establish a future colony, is critical for the survival of corals. However, in contrast to the situation in other animals, e.g., frogs and insects, little is known about the molecular basis of coral metamorphosis. We have begun to redress this situation with previous microarray studies, but there is still a great deal to learn. In the present paper we have utilized a different technology, subtractive hybridization, to characterize genes differentially expressed across this developmental transition and to compare the success of this method to microarray. METHODOLOGY/PRINCIPAL FINDINGS: Suppressive subtractive hybridization (SSH) was used to identify two pools of transcripts from the coral, Acropora millepora. One is enriched for transcripts expressed at higher levels at the pre-settlement stage, and the other for transcripts expressed at higher levels at the post-settlement stage. Virtual northern blots were used to demonstrate the efficacy of the subtractive hybridization technique. Both pools contain transcripts coding for proteins in various functional classes but transcriptional regulatory proteins were represented more frequently in the post-settlement pool. Approximately 18% of the transcripts showed no significant similarity to any other sequence on the public databases. Transcripts of particular interest were further characterized by in situ hybridization, which showed that many are regulated spatially as well as temporally. Notably, many transcripts exhibit axially restricted expression patterns that correlate with the pool from which they were isolated. Several transcripts are expressed in patterns consistent with a role in calcification. CONCLUSIONS: We have characterized over 200 transcripts that are differentially expressed between the planula larva and post-settlement polyp of the coral, Acropora millepora. Sequence, putative function, and in some cases temporal and spatial expression are reported. PMID- 22065995 TI - Multi-locus analysis reveals a different pattern of genetic diversity for mitochondrial and nuclear DNA between wild and domestic pigs in East Asia. AB - BACKGROUND: A major reduction of genetic diversity in mtDNA occurred during the domestication of East Asian pigs. However, the extent to which genetic diversity has been lost in the nuclear genome is uncertain. To reveal levels and patterns of nucleotide diversity and to elucidate the genetic relationships and demographic history of domestic pigs and their ancestors, wild boars, we investigated 14 nuclear markers (including 8 functional genes, 2 pseudogenes and 4 intergenic regions) from 11 different chromosomes in East Asia-wide samples and pooled them with previously obtained mtDNA data for a combined analysis. PRINCIPAL FINDINGS: The results indicated that domestic pigs and wild boars possess comparable levels of nucleotide diversity across the nuclear genome, which is inconsistent with patterns that have been found in mitochondrial genome. CONCLUSIONS: This incongruence between the mtDNA and nuclear genomes is suggestive of a large-scale backcross between male wild boars and female domestic pigs in East Asia. Our data reveal the impacts of founder effects and backcross on the pig genome and help us better understand the complex demographic histories of East Asian pigs, which will be useful for future work on artificial selection. PMID- 22065996 TI - A differential concentration-dependent effect of IVIg on neutrophil functions: relevance for anti-microbial and anti-inflammatory mechanisms. AB - BACKGROUND: Polymorphonuclear neutrophils (PMN) play a key role in host defences against invading microorganisms but can also potentiate detrimental inflammatory reactions in case of excessive or misdirected responses. Intravenous immunoglobulins (IVIg) are used to treat patients with immune deficiencies and, at higher doses, in autoimmune, allergic and systemic inflammatory disorders. METHODOLOGY/PRINCIPAL FINDINGS: We used flow cytometry to examine the effects of IVIg on PMN functions and survival, using whole-blood conditions in order to avoid artifacts due to isolation procedures. IVIg at low concentrations induced PMN activation, as reflected by decreased L-selectin and increased CD11b expression at the PMN surface, oxidative burst enhancement, and prolonged cell survival. In contrast, IVIg at higher concentrations inhibited LPS-induced CD11b degranulation and oxidative burst priming, and counteracted LPS-induced PMN lifespan prolongation. CONCLUSIONS/SIGNIFICANCE: IVIg appears to have differential, concentration-dependent effects on PMN, possibly supporting the use of IVIg as either an anti-microbial or an anti-inflammatory agent. PMID- 22065997 TI - Male moth songs tempt females to accept mating: the role of acoustic and pheromonal communication in the reproductive behaviour of Aphomia sociella. AB - BACKGROUND: Members of the subfamily Galleriinae have adapted to different selective environmental pressures by devising a unique mating process. Galleriinae males initiate mating by attracting females with either chemical or acoustic signals (or a combination of both modalities). Six compounds considered candidates for the sex pheromone have recently been identified in the wing gland extracts of Aphomia sociella males. Prior to the present study, acoustic communication had not been investigated. Signals mediating female attraction were likewise unknown. METHODOLOGY/PRINCIPAL FINDINGS: Observations of A. sociella mating behaviour and recordings of male acoustic signals confirmed that males initiate the mating process. During calling behaviour (stationary wing fanning and pheromone release), males disperse pheromone from their wing glands. When a female approaches, males cease calling and begin to produce ultrasonic songs as part of the courtship behaviour. Replaying of recorded courting songs to virgin females and a comparison of the mating efficiency of intact males with males lacking tegullae proved that male ultrasonic signals stimulate females to accept mating. Greenhouse experiments with isolated pheromone glands confirmed that the male sex pheromone mediates long-range female attraction. CONCLUSION/SIGNIFICANCE: Female attraction in A. sociella is chemically mediated, but ultrasonic communication is also employed during courtship. Male ultrasonic songs stimulate female sexual display and significantly affect mating efficiency. Considerable inter-individual differences in song structure exist. These could play a role in female mate selection provided that the female's ear is able to discern them. The A. sociella mating strategy described above is unique within the subfamily Galleriinae. PMID- 22065998 TI - Interactions between Upf1 and the decapping factors Edc3 and Pat1 in Saccharomyces cerevisiae. AB - In Saccharomyces cerevisiae, mRNA transcripts with premature termination codons are targeted for deadenylation independent decapping and 5' to 3' decay in a quality control pathway termed nonsense-mediated decay (NMD). Critical factors in NMD include Upf1, Upf2, and Upf3, as well as the decapping enzyme, Dcp2/Dcp1. Loss of Upf2 or Upf3 leads to the accumulation of not only Upf1 and Dcp2 in P bodies, but also of the decapping-activators Pat1, Dhh1, and Lsm1. An interaction between Upf1 and Dcp2 has been identified, which might recruit Dcp2 to the NMD decapping complex. To determine the nature and significance of the Dcp2-Upf1 interaction, we utilized the yeast two-hybrid assay to assess Upf1 interactions with various mRNA decapping factors. We find that although Dcp2 can interact with Upf1, this interaction is indirect and is largely dependent on the Edc3 protein, which interacts with the N-terminal domain of Upf1 at an overlapping, but not identical, site as Upf2. We also found that Pat1 has an independent two-hybrid interaction with the N-terminus of Upf1. Assessment of both reporter and endogenous NMD transcripts suggest that the decapping stimulators, including Edc3 and Pat1, as well as Edc1 and Edc2, are not essential for NMD under normal conditions. This work defines a larger decapping complex involved in NMD, but indicates that components of that complex are not required for general NMD and might either regulate a subset of NMD transcripts or be essential for proper NMD under different environmental conditions. PMID- 22065999 TI - Long timescale fMRI neuronal adaptation effects in human amblyopic cortex. AB - An investigation of long timescale (5 minutes) fMRI neuronal adaptation effects, based on retinotopic mapping and spatial frequency stimuli, is presented in this paper. A hierarchical linear model was developed to quantify the adaptation effects in the visual cortex. The analysis of data involved studying the retinotopic mapping and spatial frequency adaptation effects in the amblyopic cortex. Our results suggest that, firstly, there are many cortical regions, including V1, where neuronal adaptation effects are reduced in the cortex in response to amblyopic eye stimulation. Secondly, our results show the regional contribution is different, and it seems to start from V1 and spread to the extracortex regions. Thirdly, our results show that there is greater adaptation to broadband retinotopic mapping as opposed to narrowband spatial frequency stimulation of the amblyopic eye, and we find significant correlation between fMRI response and the magnitude of the adaptation effect, suggesting that the reduced adaptation may be a consequence of the reduced response to different stimuli reported for amblyopic eyes. PMID- 22066000 TI - Association between multi-dose drug dispensing and quality of drug treatment--a register-based study. AB - BACKGROUND: In the elderly in Scandinavia, multi-dose drug dispensing (MDD) is a common alternative to ordinary prescriptions (OP). MDD patients receive their drugs in unit bags, one for each dose occasion. The prescribing procedure differs between MDD and OP. The aim of the present study was to investigate the association between MDD and quality of drug treatment (QDT). METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was performed of all inhabitants in Region Vastra Gotaland alive on December 31st 2007, aged >=65 years, with >=1 prescribed drug and >=2 health care visits for >=2 diagnoses for obstructive pulmonary disease, diabetes mellitus, and/or cardiovascular disease in 2005-2007 (n = 24,146). For each patient, drug treatment on December 31st 2007 was estimated from drugs registered in the Swedish Prescribed Drug Register. QDT was evaluated according to established quality indicators (>=10 drugs, Long acting benzodiazepines, Drugs with anticholinergic action, >=3 psychotropics, and Drugs combinations that should be avoided). Logistic regression, with adjustments for age, sex, burden of disease, and residence, was performed to investigate the association between MDD and QDT. Mean age was 77 years, 51% were females, and 20% used MDD. For all quality indicators, the proportion of patients with poor QDT was greater in patients with MDD than in patients with OP (all P<0.0001). Unadjusted and adjusted odds ratios (95% confidence intervals) for poor QDT (MDD patients vs. OP patients) ranged from 1.47 (1.30-1.65) to 7.08 (6.30-7.96) and from 1.36 (1.18-1.57) to 5.48 (4.76-6.30), respectively. CONCLUSIONS/SIGNIFICANCE: Patients with MDD have poorer QDT than patients with OP. This cannot be explained by differences in age, sex, burden of disease, or residence. These findings must be taken into account when designing alternative prescribing systems. Further research is needed to evaluate causative factors and if the findings also apply to other dose dispensing systems. PMID- 22066001 TI - Novel candidate genes associated with hippocampal oscillations. AB - The hippocampus is critical for a wide range of emotional and cognitive behaviors. Here, we performed the first genome-wide search for genes influencing hippocampal oscillations. We measured local field potentials (LFPs) using 64 channel multi-electrode arrays in acute hippocampal slices of 29 BXD recombinant inbred mouse strains. Spontaneous activity and carbachol-induced fast network oscillations were analyzed with spectral and cross-correlation methods and the resulting traits were used for mapping quantitative trait loci (QTLs), i.e., regions on the genome that may influence hippocampal function. Using genome-wide hippocampal gene expression data, we narrowed the QTLs to eight candidate genes, including Plcb1, a phospholipase that is known to influence hippocampal oscillations. We also identified two genes coding for calcium channels, Cacna1b and Cacna1e, which mediate presynaptic transmitter release and have not been shown to regulate hippocampal network activity previously. Furthermore, we showed that the amplitude of the hippocampal oscillations is genetically correlated with hippocampal volume and several measures of novel environment exploration. PMID- 22066002 TI - Effects of dietary fish oil on the depletion of carcinogenic PAH-DNA adduct levels in the liver of B6C3F1 mouse. AB - Many carcinogenic polycyclic aromatic hydrocarbons (PAHs) and their metabolites can bind covalently to DNA. Carcinogen-DNA adducts may lead to mutations in critical genes, eventually leading to cancer. In this study we report that fish oil (FO) blocks the formation of DNA adducts by detoxification of PAHs. B6C3F1 male mice were fed a FO or corn oil (CO) diet for 30 days. The animals were then treated with seven carcinogenic PAHs including benzo(a)pyrene (BaP) with one of two doses via a single intraperitoneal injection. Animals were terminated at 1, 3, or 7 d after treatment. The levels of DNA adducts were analyzed by the (32)P postlabeling assay. Our results showed that the levels of total hepatic DNA adducts were significantly decreased in FO groups compared to CO groups with an exception of low PAH dose at 3 d (P = 0.067). Total adduct levels in the high dose PAH groups were 41.36+/-6.48 (Mean+/-SEM) and 78.72+/-8.03 in 10(9) nucleotides (P = 0.011), respectively, for the FO and CO groups at 7 d. Animals treated with the low dose (2.5 fold lower) PAHs displayed similar trends. Total adduct levels were 12.21+/-2.33 in the FO group and 24.07+/-1.99 in the CO group, P = 0.008. BPDE-dG adduct values at 7 d after treatment of high dose PAHs were 32.34+/-1.94 (CO group) and 21.82+/-3.37 (FO group) in 10(9) nucleotides with P value being 0.035. Low dose groups showed similar trends for BPDE-dG adduct in the two diet groups. FO significantly enhanced gene expression of Cyp1a1 in both the high and low dose PAH groups. Gstt1 at low dose of PAHs showed high levels in FO compared to CO groups with P values being 0.014. Histological observations indicated that FO played a hepatoprotective role during the early stages. Our results suggest that FO has a potential to be developed as a cancer chemopreventive agent. PMID- 22066003 TI - Discrimination task reveals differences in neural bases of tinnitus and hearing impairment. AB - We investigated auditory perception and cognitive processing in individuals with chronic tinnitus or hearing loss using functional magnetic resonance imaging (fMRI). Our participants belonged to one of three groups: bilateral hearing loss and tinnitus (TIN), bilateral hearing loss without tinnitus (HL), and normal hearing without tinnitus (NH). We employed pure tones and frequency-modulated sweeps as stimuli in two tasks: passive listening and active discrimination. All subjects had normal hearing through 2 kHz and all stimuli were low-pass filtered at 2 kHz so that all participants could hear them equally well. Performance was similar among all three groups for the discrimination task. In all participants, a distributed set of brain regions including the primary and non-primary auditory cortices showed greater response for both tasks compared to rest. Comparing the groups directly, we found decreased activation in the parietal and frontal lobes in the participants with tinnitus compared to the HL group and decreased response in the frontal lobes relative to the NH group. Additionally, the HL subjects exhibited increased response in the anterior cingulate relative to the NH group. Our results suggest that a differential engagement of a putative auditory attention and short-term memory network, comprising regions in the frontal, parietal and temporal cortices and the anterior cingulate, may represent a key difference in the neural bases of chronic tinnitus accompanied by hearing loss relative to hearing loss alone. PMID- 22066004 TI - Thermodynamic concepts in the study of microbial populations: age structure in Plasmodium falciparum infected red blood cells. AB - Variability is a hallmark of microbial systems. On the one hand, microbes are subject to environmental heterogeneity and undergo changeable conditions in their immediate surroundings. On the other hand, microbial populations exhibit high cellular diversity. The relation between microbial diversity and variability of population dynamics is difficult to assess. This connection can be quantitatively studied from a perspective that combines in silico models and thermodynamic methods and interpretations. The infection process of Plasmodium falciparum parasitizing human red blood cells under laboratory cultivation conditions is used to illustrate the potential of Individual-based models in the context of predictive microbiology and parasitology. Experimental data from several in vitro cultures are compared to the outcome of an individual-based model and analysed from a thermodynamic perspective. This approach allows distinguishing between intrinsic and external constraints that give rise to the diversity in the infection forms, and it provides a criterion to quantitatively define transient and stationary regimes in the culture. Increasing the ability of models to discriminate between different states of microbial populations enhances their predictive capability which finally leads to a better the control over culture systems. The strategy here presented is of general application and it can substantially improve modelling of other types of microbial communities. PMID- 22066005 TI - Effects of non-local diffusion on structural MRI preprocessing and default network mapping: statistical comparisons with isotropic/anisotropic diffusion. AB - Neuroimaging community usually employs spatial smoothing to denoise magnetic resonance imaging (MRI) data, e.g., Gaussian smoothing kernels. Such an isotropic diffusion (ISD) based smoothing is widely adopted for denoising purpose due to its easy implementation and efficient computation. Beyond these advantages, Gaussian smoothing kernels tend to blur the edges, curvature and texture of images. Researchers have proposed anisotropic diffusion (ASD) and non-local diffusion (NLD) kernels. We recently demonstrated the effect of these new filtering paradigms on preprocessing real degraded MRI images from three individual subjects. Here, to further systematically investigate the effects at a group level, we collected both structural and functional MRI data from 23 participants. We first evaluated the three smoothing strategies' impact on brain extraction, segmentation and registration. Finally, we investigated how they affect subsequent mapping of default network based on resting-state functional MRI (R-fMRI) data. Our findings suggest that NLD-based spatial smoothing maybe more effective and reliable at improving the quality of both MRI data preprocessing and default network mapping. We thus recommend NLD may become a promising method of smoothing structural MRI images of R-fMRI pipeline. PMID- 22066006 TI - Evolution of interactions and cooperation in the spatial prisoner's dilemma game. AB - We study the evolution of cooperation in the spatial prisoner's dilemma game where players are allowed to establish new interactions with others. By employing a simple coevolutionary rule entailing only two crucial parameters, we find that different selection criteria for the new interaction partners as well as their number vitally affect the outcome of the game. The resolution of the social dilemma is most probable if the selection favors more successful players and if their maximally attainable number is restricted. While the preferential selection of the best players promotes cooperation irrespective of game parametrization, the optimal number of new interactions depends somewhat on the temptation to defect. Our findings reveal that the "making of new friends" may be an important activity for the successful evolution of cooperation, but also that partners must be selected carefully and their number limited. PMID- 22066007 TI - Nevirapine plasma concentrations are associated with virologic response and hepatotoxicity in Chinese patients with HIV infection. AB - BACKGROUND: Limited information is available on the relationship between nevirapine plasma concentrations and virologic response or liver toxicity in Chinese patients with HIV infection. The objective of this prospective study was to test this relationship and to determine the minimal therapeutic trough concentration of nevirapine for Chinese patients. METHODS: A total of 227 HIV infected, treatment naive patients were enrolled into this study. Blood samples were taken at C(trough) (12 hr postdose) and C(2) (2 hr postdose) for measurement of nevirapine concentrations 6 months after treatment initiation. Therapeutic outcomes, viral load and CD4 cell count, were assessed at 3 and 6 months after starting therapy, while the evaluation of hepatotoxicity was undertaken 12 months after nevirapine treatment. RESULTS: A significant correlation between nevirapine trough concentrations and viral load was noticed after 6 months of treatment, particularly in patients with partial response and viral failure (p<0.01). The therapeutic C(trough) of nevirapine for Chinese patients was determined to be 3.9 ug/ml using the receiver operating characteristic curve. Virologic failure was observed in 21% (6/29) of patients with low nevirapine concentrations (<3.9 ug/ml) versus 5% (4/87) in patients with concentrations higher than 3.9 ug/ml (p = 0.015). Hepatotoxicity was significantly associated with the median nevirapine trough concentrations among male patients (8.20 vs. 5.48 ug/ml, p = 0.015) and hepatitis C virus co-infection (p = 0.039). CONCLUSIONS: Among Chinese patients with HIV infection, the therapeutic C(trough) of nevirapine was 3.9 ug/ml, higher than the recommended 3.0 ug/ml. The correlation between nevirapine concentrations, efficacy and hepatotoxicity suggests the benefit of dosage adjustment based on therapeutic drug monitoring among Chinese HIV-infected patients to optimize nevirapine containing antiretroviral therapy. PMID- 22066008 TI - A photolyase-like protein from Agrobacterium tumefaciens with an iron-sulfur cluster. AB - Photolyases and cryptochromes are evolutionarily related flavoproteins with distinct functions. While photolyases can repair UV-induced DNA lesions in a light-dependent manner, cryptochromes regulate growth, development and the circadian clock in plants and animals. Here we report about two photolyase related proteins, named PhrA and PhrB, found in the phytopathogen Agrobacterium tumefaciens. PhrA belongs to the class III cyclobutane pyrimidine dimer (CPD) photolyases, the sister class of plant cryptochromes, while PhrB belongs to a new class represented in at least 350 bacterial organisms. Both proteins contain flavin adenine dinucleotide (FAD) as a primary catalytic cofactor, which is photoreduceable by blue light. Spectral analysis of PhrA confirmed the presence of 5,10-methenyltetrahydrofolate (MTHF) as antenna cofactor. PhrB comprises also an additional chromophore, absorbing in the short wavelength region but its spectrum is distinct from known antenna cofactors in other photolyases. Homology modeling suggests that PhrB contains an Fe-S cluster as cofactor which was confirmed by elemental analysis and EPR spectroscopy. According to protein sequence alignments the classical tryptophan photoreduction pathway is present in PhrA but absent in PhrB. Although PhrB is clearly distinguished from other photolyases including PhrA it is, like PhrA, required for in vivo photoreactivation. Moreover, PhrA can repair UV-induced DNA lesions in vitro. Thus, A. tumefaciens contains two photolyase homologs of which PhrB represents the first member of the cryptochrome/photolyase family (CPF) that contains an iron-sulfur cluster. PMID- 22066009 TI - Longitudinal analysis of QuantiFERON-TB Gold In-Tube in children with adult household tuberculosis contact in South Africa: a prospective cohort study. AB - BACKGROUND: QuantiFERON-TB Gold In Tube (QFT-GIT) is a tool for detecting M. tuberculosis infection. However, interpretation and utility of serial QFT-GIT testing of pediatric tuberculosis (TB) contacts is not well understood. We compared TB prevalence between baseline and 6 months follow-up using QFT-GIT and tuberculin skin testing (TST) in children who were household contacts of adults with pulmonary TB in South Africa, and explored factors associated with QFT-GIT conversions and reversions. METHOD: Prospective study with six month longitudinal follow-up. RESULTS: Among 270 enrolled pediatric contacts, 196 (73%) underwent 6 month follow-up testing. The 6-month prevalence estimate of MTB infection in pediatric contacts increased significantly from a baseline of 29% (79/270, 95%CI [24-35]) to 38% (103/270, 95% CI [32-44], p<0.001) using QFT-GIT; prevalence increased from a baseline of 28% (71/254, 95%CI [23-34]) to 33% (88/263, 95%CI [21-32], p = 0.002) using TST. Prevalence estimates were influenced by thresholds for positivity for TST, but not for QFT-GIT. Among 134 children with a negative or indeterminate baseline QFT-GIT, 24 (18%) converted to positive at follow-up; conversion rates did not differ significantly when using more stringent thresholds to define QFT-GIT conversion. Older age >10 years (AOR 8.9 95%CI [1.1 72]) and baseline TST positivity >=5 mm (AOR 5.2 95%CI [1.2-23]) were associated with QFT-GIT conversion. Among 62 children with a positive baseline QFT-GIT, 9 (15%) reverted to negative; female gender (AOR 18.5 95%CI [1.1-321]; p = 0.04] was associated with reversion, while children with baseline positive TST were less likely to have QFT-GIT reversion (AOR 0.01 95%CI [0.001-0.24]). CONCLUSION: Among pediatric contacts of adult household TB cases in South Africa, prevalence estimates of TB infection increased significantly from baseline to 6 months. Conversions and reversions occurred among pediatric TB contacts using QFT-GIT, but QFT-GIT conversion rates were less influenced by thresholds used for conversions than were TST conversion rates. PMID- 22066010 TI - Pathobiological implications of MUC16 expression in pancreatic cancer. AB - MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease. PMID- 22066011 TI - Clinical validation of integrated nucleic acid and protein detection on an electrochemical biosensor array for urinary tract infection diagnosis. AB - BACKGROUND: Urinary tract infection (UTI) is a common infection that poses a substantial healthcare burden, yet its definitive diagnosis can be challenging. There is a need for a rapid, sensitive and reliable analytical method that could allow early detection of UTI and reduce unnecessary antibiotics. Pathogen identification along with quantitative detection of lactoferrin, a measure of pyuria, may provide useful information towards the overall diagnosis of UTI. Here, we report an integrated biosensor platform capable of simultaneous pathogen identification and detection of urinary biomarker that could aid the effectiveness of the treatment and clinical management. METHODOLOGY/PRINCIPAL FINDINGS: The integrated pathogen 16S rRNA and host lactoferrin detection using the biosensor array was performed on 113 clinical urine samples collected from patients at risk for complicated UTI. For pathogen detection, the biosensor used sandwich hybridization of capture and detector oligonucleotides to the target analyte, bacterial 16S rRNA. For detection of the protein biomarker, the biosensor used an analogous electrochemical sandwich assay based on capture and detector antibodies. For this assay, a set of oligonucleotide probes optimized for hybridization at 37 degrees C to facilitate integration with the immunoassay was developed. This probe set targeted common uropathogens including E. coli, P. mirabilis, P. aeruginosa and Enterococcus spp. as well as less common uropathogens including Serratia, Providencia, Morganella and Staphylococcus spp. The biosensor assay for pathogen detection had a specificity of 97% and a sensitivity of 89%. A significant correlation was found between LTF concentration measured by the biosensor and WBC and leukocyte esterase (p<0.001 for both). CONCLUSION/SIGNIFICANCE: We successfully demonstrate simultaneous detection of nucleic acid and host immune marker on a single biosensor array in clinical samples. This platform can be used for multiplexed detection of nucleic acid and protein as the next generation of urinary tract infection diagnostics. PMID- 22066012 TI - c-Rel controls multiple discrete steps in the thymic development of Foxp3+ CD4 regulatory T cells. AB - The development of natural Foxp3(+) CD4 regulatory T cells (nTregs) proceeds via two steps that involve the initial antigen dependent generation of CD25(+)GITR(hi)Foxp3(-)CD4(+) nTreg precursors followed by the cytokine induction of Foxp3. Using mutant mouse models that lack c-Rel, the critical NF-kappaB transcription factor required for nTreg differentiation, we establish that c-Rel regulates both of these developmental steps. c-Rel controls the generation of nTreg precursors via a haplo-insufficient mechanism, indicating that this step is highly sensitive to c-Rel levels. However, maintenance of c-Rel in an inactive state in nTreg precursors demonstrates that it is not required for a constitutive function in these cells. While the subsequent IL-2 induction of Foxp3 in nTreg precursors requires c-Rel, this developmental transition does not coincide with the nuclear expression of c-Rel. Collectively, our results support a model of nTreg differentiation in which c-Rel generates a permissive state for foxp3 transcription during the development of nTreg precursors that influences the subsequent IL-2 dependent induction of Foxp3 without a need for c-Rel reactivation. PMID- 22066013 TI - Cost-of-illness analysis of type 2 diabetes mellitus in Iran. AB - INTRODUCTION: Diabetes is a worldwide high prevalence chronic progressive disease that poses a significant challenge to healthcare systems. The aim of this study is to provide a detailed economic burden of diagnosed type 2 diabetes mellitus (T2DM) and its complications in Iran in 2009 year. METHODS: This is a prevalence based cost-of-illness study focusing on quantifying direct health care costs by bottom-up approach. Data on inpatient hospital services, outpatient clinic visits, physician services, drugs, laboratory test, education and non-medical cost were collected from two national registries. The human capital approach was used to calculate indirect costs separately in male and female and also among different age groups. RESULTS: The total national cost of diagnosed T2DM in 2009 is estimated at 3.78 billion USA dollars (USD) including 2.04+/-0.28 billion direct (medical and non-medical) costs and indirect costs of 1.73 million. Average direct and indirect cost per capita was 842.6+/-102 and 864.8 USD respectively. Complications (48.9%) and drugs (23.8%) were main components of direct cost. The largest components of medical expenditures attributed to diabetes's complications are cardiovascular disease (42.3% of total Complications cost), nephropathy (23%) and ophthalmic complications (14%). Indirect costs include temporarily disability (335.7 million), permanent disability (452.4 million) and reduced productivity due to premature mortality (950.3 million). CONCLUSIONS: T2DM is a costly disease in the Iran healthcare system and consume more than 8.69% of total health expenditure. In addition to these quantified costs, T2DM imposes high intangible costs on society in terms of reduced quality of life. Identification of effective new strategies for the control of diabetes and its complications is a public health priority. PMID- 22066014 TI - Relating neuronal to behavioral performance: variability of optomotor responses in the blowfly. AB - Behavioral responses of an animal vary even when they are elicited by the same stimulus. This variability is due to stochastic processes within the nervous system and to the changing internal states of the animal. To what extent does the variability of neuronal responses account for the overall variability at the behavioral level? To address this question we evaluate the neuronal variability at the output stage of the blowfly's (Calliphora vicina) visual system by recording from motion-sensitive interneurons mediating head optomotor responses. By means of a simple modelling approach representing the sensory-motor transformation, we predict head movements on the basis of the recorded responses of motion-sensitive neurons and compare the variability of the predicted head movements with that of the observed ones. Large gain changes of optomotor head movements have previously been shown to go along with changes in the animals' activity state. Our modelling approach substantiates that these gain changes are imposed downstream of the motion-sensitive neurons of the visual system. Moreover, since predicted head movements are clearly more reliable than those actually observed, we conclude that substantial variability is introduced downstream of the visual system. PMID- 22066015 TI - Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. AB - Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS. PMID- 22066016 TI - Spleen-resident CD4+ and CD4- CD8alpha- dendritic cell subsets differ in their ability to prime invariant natural killer T lymphocytes. AB - One important function of conventional dendritic cells (cDC) is their high capacity to capture, process and present Ag to T lymphocytes. Mouse splenic cDC subtypes, including CD8alpha(+) and CD8alpha(-) cDC, are not identical in their Ag presenting and T cell priming functions. Surprisingly, few studies have reported functional differences between CD4(-) and CD4(+) CD8alpha(-) cDC subsets. We show that, when loaded in vitro with OVA peptide or whole protein, and in steady-state conditions, splenic CD4(-) and CD4(+) cDC are equivalent in their capacity to prime and direct CD4(+) and CD8(+) T cell differentiation. In contrast, in response to alpha-galactosylceramide (alpha-GalCer), CD4(-) and CD4(+) cDC differentially activate invariant Natural Killer T (iNKT) cells, a population of lipid-reactive non-conventional T lymphocytes. Both cDC subsets equally take up alpha-GalCer in vitro and in vivo to stimulate the iNKT hybridoma DN32.D3, the activation of which depends solely on TCR triggering. On the other hand, and relative to their CD4(+) counterparts, CD4(-) cDC more efficiently stimulate primary iNKT cells, a phenomenon likely due to differential production of co-factors (including IL-12) by cDC. Our data reveal a novel functional difference between splenic CD4(+) and CD4(-) cDC subsets that may be important in immune responses. PMID- 22066017 TI - Heritability and artificial selection on ambulatory dispersal distance in Tetranychus urticae: effects of density and maternal effects. AB - Dispersal distance is understudied although the evolution of dispersal distance affects the distribution of genetic diversity through space. Using the two spotted spider mite, Tetranychus urticae, we tested the conditions under which dispersal distance could evolve. To this aim, we performed artificial selection based on dispersal distance by choosing 40 individuals (out of 150) that settled furthest from the home patch (high dispersal, HDIS) and 40 individuals that remained close to the home patch (low dispersal, LDIS) with three replicates per treatment. We did not observe a response to selection nor a difference between treatments in life-history traits (fecundity, survival, longevity, and sex-ratio) after ten generations of selection. However, we show that heritability for dispersal distance depends on density. Heritability for dispersal distance was low and non-significant when using the same density as the artificial selection experiments while heritability becomes significant at a lower density. Furthermore, we show that maternal effects may have influenced the dispersal behaviour of the mites. Our results suggest primarily that selection did not work because high density and maternal effects induced phenotypic plasticity for dispersal distance. Density and maternal effects may affect the evolution of dispersal distance and should be incorporated into future theoretical and empirical studies. PMID- 22066018 TI - Effects of elevated temperature and carbon dioxide on the growth and survival of larvae and juveniles of three species of northwest Atlantic bivalves. AB - Rising CO(2) concentrations and water temperatures this century are likely to have transformative effects on many coastal marine organisms. Here, we compared the responses of two life history stages (larval, juvenile) of three species of calcifying bivalves (Mercenaria mercenaria, Crassostrea virginica, and Argopecten irradians) to temperatures (24 and 28 degrees C) and CO(2) concentrations (~250, 390, and 750 ppm) representative of past, present, and future summer conditions in temperate estuaries. Results demonstrated that increases in temperature and CO(2) each significantly depressed survival, development, growth, and lipid synthesis of M. mercenaria and A. irradians larvae and that the effects were additive. Juvenile M. mercenaria and A. irradians were negatively impacted by higher temperatures while C. virginica juveniles were not. C. virginica and A. irradians juveniles were negatively affected by higher CO(2) concentrations, while M. mercenaria was not. Larvae were substantially more vulnerable to elevated CO(2) than juvenile stages. These findings suggest that current and future increases in temperature and CO(2) are likely to have negative consequences for coastal bivalve populations. PMID- 22066019 TI - Boswellic acid suppresses growth and metastasis of human pancreatic tumors in an orthotopic nude mouse model through modulation of multiple targets. AB - Pancreatic cancer (PaCa) is one of the most lethal cancers, with an estimated 5 year survival of <5% even when patients are given the best treatment available. In addition, these treatments are often toxic and expensive, thus new agents which are safe, affordable and effective are urgently needed. We describe here the results of our study with acetyl-11-keto-beta-boswellic acid (AKBA), an agent obtained from an Ayurvedic medicine, gum resin of Boswellia serrata. Whether AKBA has an activity against human PaCa, was examined in in vitro models and in an orthotopic nude mouse model of PaCa. We found that AKBA inhibited the proliferation of four different PaCa cell lines (AsPC-1, PANC-28, and MIA PaCa-2 with K-Ras and p53 mutations, and BxPC-3 with wild-type K-Ras and p53 mutation). These effects correlated with an inhibition of constitutively active NF-kappaB and suppression of NF-kappaB regulating gene expression. AKBA also induced apoptosis, and sensitized the cells to apoptotic effects of gemcitabine. In the orthotopic nude mouse model of PaCa, p.o. administration of AKBA alone (100 mg/kg) significantly inhibited the tumor growth; this activity was enhanced by gemcitabine. In addition, AKBA inhibited the metastasis of the PaCa to spleen, liver, and lungs. This correlated with decreases in Ki-67, a biomarker of proliferation, and CD31, a biomarker of microvessel density, in the tumor tissue. AKBA produced significant decreases in the expression of NF-kappaB regulating genes in the tissues. Immunohistochemical analysis also showed AKBA downregulated the expression of COX-2, MMP-9, CXCR4, and VEGF in the tissues. Overall these results demonstrate that AKBA can suppress the growth and metastasis of human pancreatic tumors in an orthotopic nude mouse model that correlates with modulation of multiple targets. PMID- 22066020 TI - Accuracy and cut-off values of pepsinogens I, II and gastrin 17 for diagnosis of gastric fundic atrophy: influence of gastritis. AB - BACKGROUND: To establish optimal cutoff values for serologic diagnosis of fundic atrophy in a high-risk area for oesophageal squamous cell carcinoma and gastric cancer with high prevalence of Helicobacter pylori (H. pylori) in Northern Iran, we performed an endoscopy-room-based validation study. METHODS: We measured serum pepsinogens I (PGI) and II (PGII), gastrin 17 (G-17), and antibodies against whole H. pylori, or cytotoxin-associated gene A (CagA) antigen among 309 consecutive patients in two major endoscopy clinics in northeastern Iran. Updated Sydney System was used as histology gold standard. Areas under curves (AUCs), optimal cutoff and predictive values were calculated for serum biomarkers against the histology. RESULTS: 309 persons were recruited (mean age: 63.5 years old, 59.5% female). 84.5% were H. pylori positive and 77.5% were CagA positive. 21 fundic atrophy and 101 nonatrophic pangastritis were diagnosed. The best cutoff values in fundic atrophy assessment were calculated at PGI<56 ug/l (sensitivity: 61.9%, specificity: 94.8%) and PGI/PGII ratio<5 (sensitivity: 75.0%, specificity: 91.0%). A serum G-17<2.6 pmol/l or G-17>40 pmol/l was 81% sensitive and 73.3% specific for diagnosing fundic atrophy. At cutoff concentration of 11.8 ug/l, PGII showed 84.2% sensitivity and 45.4% specificity to distinguish nonatrophic pangastritis. Exclusion of nonatrophic pangastritis enhanced diagnostic ability of PGI/PGII ratio (from AUC = 0.66 to 0.90) but did not affect AUC of PGI. After restricting study samples to those with PGII<11.8, the sensitivity of using PGI<56 to define fundic atrophy increased to 83.3% (95%CI 51.6-97.9) and its specificity decreased to 88.8% (95%CI 80.8-94.3). CONCLUSIONS: Among endoscopy clinic patients, PGII is a sensitive marker for extension of nonatrophic gastritis toward the corpus. PGI is a stable biomarker in assessment of fundic atrophy and has similar accuracy to PGI/PGII ratio among populations with prevalent nonatrophic pangastritis. PMID- 22066021 TI - Defence responses of Arabidopsis thaliana to infection by Pseudomonas syringae are regulated by the circadian clock. AB - The circadian clock allows plants to anticipate predictable daily changes in abiotic stimuli, such as light; however, whether the clock similarly allows plants to anticipate interactions with other organisms is unknown. Here we show that Arabidopsis thaliana (Arabidopsis) has circadian clock-mediated variation in resistance to the virulent bacterial pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000), with plants being least susceptible to infection in the subjective morning. We suggest that the increased resistance to Pst DC3000 observed in the morning in Col-0 plants results from clock-mediated modulation of pathogen associated molecular pattern (PAMP)-triggered immunity. Analysis of publicly available microarray data revealed that a large number of Arabidopsis defence-related genes showed both diurnal- and circadian-regulation, including genes involved in the perception of the PAMP flagellin which exhibit a peak in expression in the morning. Accordingly, we observed that PAMP-triggered callose deposition was significantly higher in wild-type plants inoculated with Pst DC3000 hrpA in the subjective morning than in the evening, while no such temporal difference was evident in arrhythmic plants. Our results suggest that PAMP triggered immune responses are modulated by the circadian clock and that temporal regulation allows plants to anticipate and respond more effectively to pathogen challenges in the daytime. PMID- 22066022 TI - Serum microRNA-21 as marker for necroinflammation in hepatitis C patients with and without hepatocellular carcinoma. AB - BACKGROUND: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC. METHODOLOGY/PRINCIPAL FINDINGS: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR 21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = -0.494, P = 0.00002), alanine aminotransferase (ALT) (r = -0.309, P = 0.007), aspartate aminotransferase (r = -0.495, P = 0.000007), bilirubin (r = -0.362, P = 0.002), international normalized ratio (r = -0.338, P = 0.034) and gamma glutamyltransferase (r = -0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dC(T) of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%. CONCLUSIONS/SIGNIFICANCE: The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV induced HCC. PMID- 22066023 TI - CCL28 induces mucosal homing of HIV-1-specific IgA-secreting plasma cells in mice immunized with HIV-1 virus-like particles. AB - Mucosae-associated epithelial chemokine (MEC or CCL28) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASCs) in the mucosal lamina propria. The ability of this chemokine to enhance migration of IgA-ASCs to mucosal sites was assessed in a mouse immunization model using HIV-1(IIIB) Virus-like particles (VLPs). Mice receiving either HIV-1(IIIB) VLPs alone, CCL28 alone, or the irrelevant CCL19 chemokine were used as controls. Results showed a significantly increased CCR3 and CCR10 expression on CD19(+) splenocytes of HIV-1(IIIB) VPL CCL28-treated mice. HIV-1 Env-specific IFN-gamma, IL-4 and IL-5 production, total IgA, anti-Env IgA as well as gastro-intestinal mucosal IgA-secreting plasma cells were also significantly augmented in these mice. Notably, sera and vaginal secretions from HIV-1(IIIB) VLP-CCL28-treated mice exhibited an enhanced neutralizing activity against both a HIV-1/B-subtype laboratory strain and a heterologous HIV-1/C-subtype primary isolate. These data suggest that CCL28 could be useful in enhancing the IgA immune response that will likely play a pivotal role in prophylactic HIV vaccines. PMID- 22066024 TI - Legacy effects of canopy disturbance on ecosystem functioning in macroalgal assemblages. AB - Macroalgal assemblages are some of the most productive systems on earth and they contribute significantly to nearshore ecosystems. Globally, macroalgal assemblages are increasingly threatened by anthropogenic activities such as sedimentation, eutrophication and climate change. Despite this, very little research has considered the potential effects of canopy loss on primary productivity, although the literature is rich with evidence showing the ecological effects of canopy disturbance. In this study we used experimental removal plots of habitat-dominating algae (Order Fucales) that had been initiated several years previously to construct a chronosequence of disturbed macroalgal communities and to test if there were legacy effects of canopy loss on primary productivity. We used in situ photo-respirometry to test the primary productivity of algal assemblages in control and removal plots at two intertidal elevations. In the mid tidal zone assemblage, the removal plots at two sites had average primary productivity values of only 40% and 60% that of control areas after 90 months. Differences in productivity were associated with lower biomass and density of the fucoid algal canopy and lower taxa richness in the removal plots after 90 months. Low-shore plots, established three years earlier, showed that the loss of the large, dominant fucoid resulted in at least 50% less primary productivity of the algal assemblage than controls, which lasted for 90 months; other smaller fucoid species had recruited but they were far less productive. The long term reduction in primary productivity following a single episode of canopy loss of a dominant species in two tidal zones suggests that these assemblages are not very resilient to large perturbations. Decreased production output may have severe and long-lasting consequences on the surrounding communities and has the potential to alter nutrient cycling in the wider nearshore environment. PMID- 22066025 TI - Amelioration of experimental autoimmune encephalomyelitis by plumbagin through down-regulation of JAK-STAT and NF-kappaB signaling pathways. AB - Plumbagin (PL), a herbal compound derived from roots of the medicinal plant Plumbago zeylanica, has been shown to have immunosuppressive properties. Present report describes that PL is a potent novel agent in control of encephalitogenic T cell responses and amelioration of mouse experimental autoimmune encephalomyelitis (EAE), through down-regulation of JAK-STAT pathway. PL was found to selectively inhibit IFN-gamma and IL-17 production by CD4(+) T cells, which was mediated through abrogated phosphorylation of JAK1 and JAK2. Consistent with IFN-gamma and IL-17 reduction was suppressed STAT1/STAT4/T-bet pathway which is critical for Th1 differentiation, as well as STAT3/ROR pathway which is essential for Th17 differentiation. In addition, PL suppressed pro-inflammatory molecules such as iNOS, IFN-gamma and IL-6, accompanied by inhibition of IkappaB degradation as well as NF-kappaB phosphorylation. These data give new insight into the novel immune regulatory mechanism of PL and highlight the great value of this kind of herb compounds in probing the complex cytokine signaling network and novel therapeutic targets for autoimmune diseases. PMID- 22066026 TI - Normal mouse intestinal epithelial cells as a model for the in vitro invasion of Trichinella spiralis infective larvae. AB - It has been known for many years that Trichinella spiralis initiates infection by penetrating the columnar epithelium of the small intestine; however, the mechanisms used by the parasite in the establishment of its intramulticellular niche in the intestine are unknown. Although the previous observations indicated that invasion also occurs in vitro when the infective larvae are inoculated onto cultures of intestinal epithelial cells (e.g., human colonic carcinoma cell line Caco-2, HCT-8), a normal readily manipulated in vitro model has not been established because of difficulties in the culture of primary intestinal epithelial cells (IECs). In this study, we described a normal intestinal epithelial model in which T. spiralis infective larvae were shown to invade the monolayers of normal mouse IECs in vitro. The IECs derived from intestinal crypts of fetal mouse small intestine had the ability to proliferate continuously and express specific cytokeratins as well as intestinal functional cell markers. Furthermore, they were susceptible to invasion by T. spiralis. When inoculated onto the IEC monolayer, infective larvae penetrated cells and migrated through them, leaving trails of damaged cells heavily loaded with T. spiralis larval excretory-secretory (ES) antigens which were recognized by rabbit immune sera on immunofluorescence test. The normal intestinal epithelial model of invasion mimicking the natural environment in vivo will help us to further investigate the process as well as the mechanisms by which T. spiralis establishes its intestinal niche. PMID- 22066027 TI - Hands-on parameter search for neural simulations by a MIDI-controller. AB - Computational neuroscientists frequently encounter the challenge of parameter fitting--exploring a usually high dimensional variable space to find a parameter set that reproduces an experimental data set. One common approach is using automated search algorithms such as gradient descent or genetic algorithms. However, these approaches suffer several shortcomings related to their lack of understanding the underlying question, such as defining a suitable error function or getting stuck in local minima. Another widespread approach is manual parameter fitting using a keyboard or a mouse, evaluating different parameter sets following the users intuition. However, this process is often cumbersome and time intensive. Here, we present a new method for manual parameter fitting. A MIDI controller provides input to the simulation software, where model parameters are then tuned according to the knob and slider positions on the device. The model is immediately updated on every parameter change, continuously plotting the latest results. Given reasonably short simulation times of less than one second, we find this method to be highly efficient in quickly determining good parameter sets. Our approach bears a close resemblance to tuning the sound of an analog synthesizer, giving the user a very good intuition of the problem at hand, such as immediate feedback if and how results are affected by specific parameter changes. In addition to be used in research, our approach should be an ideal teaching tool, allowing students to interactively explore complex models such as Hodgkin-Huxley or dynamical systems. PMID- 22066028 TI - Dystrophin is required for the normal function of the cardio-protective K(ATP) channel in cardiomyocytes. AB - Duchenne and Becker muscular dystrophy patients often develop a cardiomyopathy for which the pathogenesis is still unknown. We have employed the murine animal model of Duchenne muscular dystrophy (mdx), which develops a cardiomyopathy that includes some characteristics of the human disease, to study the molecular basis of this pathology. Here we show that the mdx mouse heart has defects consistent with alteration in compounds that regulate energy homeostasis including a marked decrease in creatine-phosphate (PC). In addition, the mdx heart is more susceptible to anoxia than controls. Since the cardio-protective ATP sensitive potassium channel (K(ATP)) complex and PC have been shown to interact we investigated whether deficits in PC levels correlate with other molecular events including K(ATP) ion channel complex presence, its functionality and interaction with dystrophin. We found that this channel complex is present in the dystrophic cardiac cell membrane but its ability to sense a drop in the intracellular ATP concentration and consequently open is compromised by the absence of dystrophin. We further demonstrate that the creatine kinase muscle isoform (CKm) is displaced from the plasma membrane of the mdx cardiac cells. Considering that CKm is a determinant of K(ATP) channel complex function we hypothesize that dystrophin acts as a scaffolding protein organizing the K(ATP) channel complex and the enzymes necessary for its correct functioning. Therefore, the lack of proper functioning of the cardio-protective K(ATP) system in the mdx cardiomyocytes may be part of the mechanism contributing to development of cardiac disease in dystrophic patients. PMID- 22066029 TI - Predicting a positive response to intravenous immunoglobulin in isolated lower motor neuron syndromes. AB - OBJECTIVE: To determine clinically related characteristics in patients with pure lower motor neuron (LMN) syndromes, not fulfilling accepted diagnostic criteria, who were likely to respond to intravenous immunoglobulin (IVIg) treatment. METHODS: Demographic, clinical, laboratory and neurophysiological characteristics were prospectively collected from patients with undifferentiated isolated LMN syndromes who were then treated with IVIg. Patients were classified as either responders or non-responders to therapy with IVIg based on clinical data and the two groups were compared. RESULTS: From a total cohort of 42 patients (30 males, 12 females, aged 18-83 years), 31 patients responded to IVIg and 11 did not. Compared to patients that developed progressive neurological decline, responders were typically younger (45.8 compared to 56.0 years, P<0.05) and had upper limb (83.9% compared to 63.6%, NS), unilateral (80.6% compared to 45.5%, P<0.05), and isolated distal (54.1% compared to 9.1%, P<0.05) weakness. Patients with predominantly upper limb, asymmetrical, and distal weakness were more likely to respond to IVIg therapy. Of the patients who responded to treatment, only 12.9% had detectable GM(1) antibodies and conduction block (not fulfilling diagnostic criteria) was only identified in 22.6%. CONCLUSIONS: More than 70% of patients with pure LMN syndromes from the present series responded to treatment with IVIg therapy, despite a low prevalence of detectable GM(1) antibodies and conduction block. Patients with isolated LMN presentations, not fulfilling accepted diagnostic criteria, may respond to IVIg therapy, irrespective of the presence of conduction block or GM(1) antibodies, and should be given an empirical trial of IVIg to determine treatment responsiveness. PMID- 22066030 TI - Individual differences and metacognitive knowledge of visual search strategy. AB - A crucial ability for an organism is to orient toward important objects and to ignore temporarily irrelevant objects. Attention provides the perceptual selectivity necessary to filter an overwhelming input of sensory information to allow for efficient object detection. Although much research has examined visual search and the 'template' of attentional set that allows for target detection, the behavior of individual subjects often reveals the limits of experimental control of attention. Few studies have examined important aspects such as individual differences and metacognitive strategies. The present study analyzes the data from two visual search experiments for a conjunctively defined target (Proulx, 2007). The data revealed attentional capture blindness, individual differences in search strategies, and a significant rate of metacognitive errors for the assessment of the strategies employed. These results highlight a challenge for visual attention studies to account for individual differences in search behavior and distractibility, and participants that do not (or are unable to) follow instructions. PMID- 22066031 TI - Benzonidazole therapy modulates interferon-gamma and M2 muscarinic receptor autoantibody responses in Trypanosoma cruzi-infected children. AB - OBJECTIVE: The presence of autoantibodies with adrenergic and cholinergic activity, capable of triggering neurotransmitter receptor-mediated effects, has been associated with pathogenesis in T. cruzi-infected hosts. The goal of this study was to investigate the production of anti-M2 muscarinic receptor autoantibodies (Anti-M2R AAbs) as well as the IFN-gamma profile in children at the early stage of Chagas disease, and to examine whether trypanocidal chemotherapy with benzonidazole (BZ) could modify both response patterns. METHODS: This study comprised 30 T. cruzi-infected children (mean age: 13.8 years) and 19 uninfected controls (mean age: 12.7 years). Infected patients were treated with BZ and followed-up. Blood samples collected at diagnosis-T0, end of treatment-T1, and six months later-T2 were analysed by ELISA for detection of Anti-M2R AAbs and circulating levels of IFN-gamma. RESULTS: At T0, anti-M2R AAbs were demonstrated in 56.7% of T. cruzi-infected patients, whereas uninfected controls were 100% negative. The average age of Anti-M2R AAbs(+) patients was higher than that from negative population. Infected children also displayed significantly stronger serum IFN-gamma responses than controls. Upon BZ treatment, a significant linear decreasing trend in Anti-M2R AAb reactivity was recorded throughout the follow-up, with 29.7-88.1% decrease at T2. IFN-gamma circulating levels also declined by T2. CONCLUSION: Anti-M2R AAbs and IFN-gamma raise early during chagasic infection in children and are downmodulated by BZ therapy. These findings reinforce the usefulness of early BZ treatment not only to eliminate the parasite but also to reduce potentially pathogenic immune responses. PMID- 22066033 TI - Conducting correlation seminars in basic sciences at KIST Medical College, Nepal. AB - KIST Medical College is a new medical school in Lalitpur, Nepal. In Nepal, six basic science subjects are taught together in an integrated organ system-based manner with early clinical exposure and community medicine. Correlation seminars are conducted at the end of covering each organ system. The topics are decided by the core academic group (consisting of members from each basic science department, the Department of Community Medicine, the academic director, and the clinical and program coordinators) considering the public health importance of the condition and its ability to include learning objectives from a maximum number of subjects. The learning objectives are decided by individual departments and finalized after the meeting of the core group. There are two student coordinators for each seminar and an evaluation group evaluates each seminar and presenter. Correlation seminars help students revise the organ system covered and understand its clinical importance, promote teamwork and organization, and supports active learning. Correlation seminars should be considered as a learning modality by other medical schools. PMID- 22066034 TI - Endometrial stromal sarcoma metastasis to the lumbar spine and sphenoid bone. AB - Endometrial stromal sarcoma (ESS) is typically associated with metastasis to the abdomen, pelvis, and lung. We found three case reports of ESS metastasis to the bone (two to the thoracic spine, and one to the parietal bone). Our objective is to review the literature on ESS spinal and intracranial metastases and, report the first case of ESS metastatic to the lumbar paraspinal region and sphenoid bone. A 53-year-old female with ESS status-post radiation, chemotherapy, and pelvic exenteration surgery presented with right hip weakness, back pain, and radicular leg pain that were explained by chemotherapy-induced neuropathy, radiation-induced lumbosacral plexopathy, and femoral nerve and obturator nerve injury during pelvic exenteration surgery. During routine positron emission tomography, we found metastasis to the L3 lumbar spinal region. L3 laminectomy and subtotal resection of the mass was performed with tumor residual in the neuroforamina and pedicles. One month later, magnetic resonance imaging (MRI) performed for persistent headaches revealed a large lesion in the sphenoid bone that was biopsied transsphenoidally with the same diagnosis, but no further surgery was performed. She is intolerant of chemotherapy and currently undergoing whole brain radiation. Delay in the diagnosis and management of lumbar paraspinal and sphenoid bone metastasis of ESS likely occurred because of the uniqueness of the location and aggressiveness of ESS metastasis. Health care providers should be aware of potentially aggressive metastasis of ESS to bone, in particular the unusual locations of the lumbar paraspinal region and sphenoid bone. PMID- 22066035 TI - Salvage surgery for a giant melanoma on the back. AB - We report a case of a giant melanoma on the back with a very extreme Breslow thickness. On physical examination a large odorous and ulcerating tumour was seen adjacent to two large crusted lesions, probably in transit metastases. In the right and left axilla enlarged lymph nodes were palpated. The patient underwent salvage surgery consisting of a complete wide excision of the tumors on the back as well as axillary lymph node dissection on both sides. Histopathology showed a malignant melanoma with a Breslow thickness of 48 mm. Four of fifteen nodes in the right axilla and one of nine nodes in the left axilla, were positive for metastatic disease. Also various in transit and subcutaneous metastases were found in the wide excision specimen. The interest of our observation relies in the rarity of a melanoma with such an extreme Breslow thickness and the difficulty in performing adequate palliative therapy that offers quality of life by means of tumor control. PMID- 22066036 TI - Efficacy of trabectedin in metastatic solitary fibrous tumor. AB - Solitary fibrous tumor is a rare tumor type and has an unpredictable course. Local recurrence rate varies between 9 and 19%, and rate of metastatic involvement between 0 and 36 %. It is characterized by a typical architecture and immuno-histochemistry tests. The most important prognostic factor is the complete resection of primary tumor. Treatment of recurrences is not clearly established. If a solitary fibrous tumor is too advanced to allow surgical resection, radiotherapy and chemotherapy may be used. The most often used drugs are doxorubicine and?or ifosfamide. We report the case of man with metastatic solitary fibrous tumor treated with trabectedin, administered at a dose of 1.5 mg/m2 every 3 weeks. After 3 cycles, metastases had significantly decreased. Recurrence of the disease was demonstrated 8 months after the start of trabectedin. This case shows that trabectedin is a possible treatment option. PMID- 22066037 TI - A pure microcytic bladder carcinoma synchronous to prostatic adenocarcinoma. AB - Small cell carcinoma (SCC) or microcytic carcinoma of the urinary bladder is a rare entity comprising approximately 0.5% of all bladder tumors. Due to its rarity, no prospective studies evaluating the most effective treatment have been published in the medical literature. Several cases of bladder SCC have been presented so far. We describe our case report and we revise the recent literature. Our patient was diagnosed with pure bladder SCC and prostatic adenocarcinoma. After the initial and complete transurethral resection of the bladder tumour (TUR-BT), he underwent a thorax and mediastinum computer tomography (CT) examination to exclude primary pulmonary small cell carcinoma and a bone scan scintigraphy for staging purposes. He received a three 14-day cycles of Cisplatin-containing chemotherapeutic schema and a single dose of Luteinizing Hormone Releasing hormone (LHRH) analogue injection after 14 days of bicalutamide administration. The patient is followed for 24 months without any signs of bladder SCC recurrence or biochemical or local relapse from prostatic adenocarcinoma. PMID- 22066038 TI - Massive recurring angiomyxoma of the scrotum in a obese man. AB - Aggressive angiomyxoma (AAM) is a rare mesenchymal benign myxoid tumor, characterized by locally infiltrative nature and high recurrence rate. AAM occurs almost exclusively in adult females, arising from the soft tissue of the pelvic region: to our knowledge, only 43 cases occurring in men have been reported. We report a case of massive recurrence of scrotal AAM in a 46-year-old obese man, who already underwent surgery for the same disease in 2004 and 2005. The mass had a circumference of 106 cm and weighted 30 kg. It was impossible to appreciate the testes and to find the penis. The patient underwent scrotal resection, bilateral orchidopexia and transposition of the penis, by means of a preputial flap. Residual scrotal skin was modeled in order to create a neoscrotum, where the testes were placed and secured with interrupted sutures. Histologic examination showed diffuse angiomyxoma-like lipomatosis. After three months, the patient presented with local relapse which also involved the external urethral orifice. PMID- 22066039 TI - Response to radiation in renal medullary carcinoma. AB - Renal medullary carcinoma (RMC) is a rare and highly aggressive malignancy arising from the renal medulla and found mostly in patients with sickle cell trait. RMC usually presents with widely metastatic disease. We describe a young man diagnosed with metastatic RMC who sustained a complete response to systemic chemotherapy but developed brain metastases with leptomeningeal involvement and subsequently had a partial response to brain irradiation. The use of radiation in the management of RMC is reviewed. Due to the apparent propensity for RMC to spread to the central nervous system, prophylactic treatment such as craniospinal irradiation should be considered along with chemotherapy in patients with metastatic RMC to potentially improve the progression-free interval. PMID- 22066040 TI - Primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy. AB - Cancer complicates approximately 0.1% of all pregnancies. Primary tracheal carcinoma is one of very rarely seen tumors and the rate of its being seen makes up approximately % 0.2 of all tumors of respiratory tract. The patient, 28 years old, who has 28-weeks-pregnant, was diagnosed with primary tracheal adenocystic carcinoma. Patient was made operation as thoracotomy and tracheal tumor was removed at the 28(th) week of pregnancy. Patient was delivered with sectio abdominale at the 39(th) week of pregnancy. Primary tracheal adenocystic carcinoma is very rarely seen tumors and it is the first tracheal ACC with pregnancy case in literature to have been detected and surgically treated during pregnancy. We discussed primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy with literature. PMID- 22066041 TI - Merkel cell carcinoma in a 17-year-old boy, report of a highly aggressive fatal case and review of the literature. AB - Merkel cell carcinoma is a rare tumor frequently involving the skin with an aggressive behavior and fatal outcome. It occurs mostly in the caucasian race between 60-80 years of age and it is rare in children. Herein we report our experience with a highly aggressive fatal Merkel cell carcinoma in an immunocompetent 17-year-old boy. Its characteristics and treatment modalities will be also discussed. PMID- 22066042 TI - The indices of body size and aggressiveness of papillary thyroid carcinoma. AB - PURPOSE: The incidence of papillary thyroid carcinoma (PTC) is increasing worldwide. Positive associations between indices of body size and thyroid cancer have been reported. However, the relationships to cancer severities and/or behaviors are uncertain. METHODS: We performed a retrospective analysis of the data of patients who underwent total thyroidectomy due to PTC. The epidemiologic factor and pathologic report after operation were determined based on chart review. The relationships between indices of body size and these parameters were assessed. RESULTS: Positive association between body mass index and T stage was found, but it was not statically significant. In neck lymph node metastasis, the group with metastasis had a tendency for larger mean height and weight, but significant difference was found only in height. However, in the multivariate analysis, the age and size of nodules were only identified as independent risk factors of neck lymph node metastasis (P = 0.000 and 0.019). CONCLUSION: There was no independent association between indices of body size and stages of PTC in patients who underwent total thyroidectomy. PMID- 22066043 TI - The effects of laparoscopic assisted total gastrectomy on surgical outcomes in the treatment of gastric cancer. AB - PURPOSE: To evaluate the effectiveness of laparoscopic assisted total gastrectomy (LATG), we compared its early surgical outcomes with those of conventional open total gastrectomy (OTG) in patients who were diagnosed as having early gastric cancer preoperatively. METHODS: We retrospectively analyzed early surgical outcomes in 190 consecutive patients who underwent total gastrectomy for early gastric cancer between January 2009 to April 2010. The patients were divided into those who underwent LATG and those who underwent OTG. Their early surgical outcomes were analyzed to evaluate the effectiveness of LATG. RESULTS: There was no significant difference in postoperative complication rates (P = 0.291). But in the analysis of other early surgical outcomes, we found that LATG could improve time to first flatus (P < 0.001), time to commencement of soft diet (P = 0.034), administration of analgesics (P = 0.024), pain score (Numeric Rating Scale), and hospital discharge (P = 0.045). CONCLUSION: Although LATG didn't show better results for postoperative complications than those of OTG, LATG contributes to the improvement of early surgical outcomes, including bowel movement, pain score and hospital discharge. Therefore, we suggest that LATG could be a method to improve early surgical outcomes in patients who need total gastrectomy. PMID- 22066044 TI - Migrating motor complex changes after side-to-side ileal bypass in mouse ileum ex vivo: mechanism underlying the blind loop syndrome? AB - PURPOSE: This study was intended to investigate the migrating motor complex (MMC) changes after ileal bypass in ex-vivo mouse models. METHODS: Partial (side-to side) and total bypass (occlusion of proximal part of bypassed loop) were performed on ileums of female Institute of Cancer Research mice. After 2 and 4 weeks, the bypassed segments were harvested and MMCs were recorded at 4 different sites ex-vivo. Amplitude, duration, interval, direction of propagation, and the area under the curve (AUC) of MMCs were measured and compared to those of the controls. RESULTS: In control mice (n = 7), most MMCs propagated aborally (91.1%). After 2 weeks of partial bypass (n = 4), there was a significant decrease in both amplitude and AUC, and orally-propagating MMCs increased significantly (45%, P = 0.002). Bidirectional MMCs (originating in the bypassed loop and propagating in both directions) were also observed (10%). The amplitude of the MMCs remained decreased at 4 weeks after partial bypass (n = 4), and neither the AUC nor the direction of propagation showed significant changes compared to 2 weeks. Similarly, in the total bypass model, both the amplitude and AUC of the MMCs decreased significantly compared to controls. In contrast to partial bypass, 95% of the MMCs within the bypassed loop propagated aborally after 2 weeks (n = 6), which was similar to the control state. After 4 weeks (n = 5), however, MMCs either lost their temporal relationship or completely disappeared. CONCLUSION: The changes in propagation direction of the MMCs in the partially bypassed loop may contribute to stagnation of bowel contents and the development of blind loop syndrome. PMID- 22066045 TI - Prognostic implication of metastatic lymph node ratio in node-positive rectal cancer. AB - PURPOSE: The aim of this study was to evaluate the prognostic significance of the ratio between metastatic and examined lymph nodes (LNs) in patients with stage III rectal cancer. METHODS: A review was made of 175 (male, 98) patients with stage III rectal cancer of R0 resection. LN disease was stratified both by the American Joint Committee on Cancer/International Union Against Cancer nodal classification (pN) and by quartiles of the lymph node ratio (LNR). Disease-free survivals (DFS) were made using Kaplan-Meier curves and assessed by the log rank test and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Patients ranged in age from 29 to 83 (median, 60) years with median follow-up of 47 months (range, 13 to 181 months). months. There was a significant correlation between the number of metastatic LNs and the LNR (r = 0.8681, P < 0.0001). Cut-off points of LNR quartiles best to separate patients with regard to 5-year DFS were between quartile 2 and 3, and between 3 and 4 (LNR1, 2, and 3); the 5-year DFS according to such stratification was 89.6%, 55.8%, and 18.2% in LNR1, 2, and 3, respectively (P < 0.0001). Cox model identified the LNR as the most significant independent prognostic covariate; LNR2 showed 3.6 times (95% confidence interval [CI], 1.682 to 7.584; P = 0.0009) and LNR3, 18.7 times (95% CI, 6.872 to 50.664; P < 0.0001) more risky than LNR1. CONCLUSION: This study suggests that ratio-based LN staging, which reflects the number of LNs examined and the quality of LN dissection, is a simple and reliable system for prognostic LN stratification in patients with stage III rectal cancer. PMID- 22066046 TI - Gynecologic pathologies in our appendectomy series and literature review. AB - PURPOSE: Appendectomy applied from the diagnosis of acute appendicitis is one the most common operations in surgery. The rates of negative appendectomy are still high. The rates of negative appendectomy in males and females differ and are higher in females. In our study, these differences, particularly in females, were studied and possible solutions were discussed. METHODS: Between October 2002 and October 2009, among women receiving urgent appendectomies, those whose primary cause was gynecological pathology were studied retrospectively. All our women subjects were examined by preoperative gynecologists. After gynecological consultation, the patients were evaluated by a general surgeon due to lack of urgent ultrasonography, computed tomography (CT) and diagnostic laparoscopy and the patient received appendectomy due to acute appendicitis. RESULTS: In our series of 1,969 appendectomies, the rate of female/male is 811/1,158. It was determined that the primary cause in 47 (47/811; 5.8%) women with applied appendectomy was gynecological pathology. As a gynecological pathology, it was observed that the most common cause was ovarian cyst ruptures at a rate of 72.3%. The negative appendectomy rate in males was found to be 14.94% (173/1,158), and in females it was 22.56% (183/811). The difference between them is significant (P < 0.01). Of these women, 5.8% were gynecologically-induced and 16.76% were unrelated to gynecological causes. CONCLUSION: We believe that gynecological consultation before appendectomy in women is necessary, but not sufficient. It is also important that at least one of the facilities, such as us, CT, magnetic resonance imaging, and diagnostic laparoscopy should be available in surgical use for the diagnosis of negative appendicitis. PMID- 22066047 TI - Multiple renal arteries challenge in laparoscopic donor nephrectomy: how far can we go? AB - PURPOSE: Living donor kidneys with multiple arteries are routinely procured laparoscopically. We aim to present our experience with laparoscopic donor nephrectomy (LDN) and to compare the graft function and outcome between cases with single versus multiple arteries. METHODS: We compared the demographic data, operation time, warm ischemia time, rejection rate, and graft function between LDN kidneys with single artery and those with multiple arteries. RESULTS: Seventy three cases with 1 renal artery (group LDN-1), 8 cases with 2 renal arteries (group LDN-2) and 5 cases with 3 or more renal arteries (group LDN-3) were included in the study. The mean operative time was significantly higher in groups LDN-2 (100.3 +/- 9.5 minutes) and LDN-3 (120.6 +/- 10.3 minutes) compared to group LDN-1 (75.7 +/- 10 minutes, P < 0.001). Similar results were detected with respect to the warm ischemia time. There were no statistically significant differences related to graft function and outcome among these groups. CONCLUSION: Multiple renal arteries present a special challenge in both donor nephrectomy and renal transplantation. However, laparoscopic procurement of a kidney with multiple renal arteries, regardless of the number, is reliable and has no significant impact on the graft outcome. PMID- 22066048 TI - Surgical resection of metastasis to the pancreas. AB - PURPOSE: Metastasis to the pancreas is rare, and the benefit of resection for pancreatic metastasis is poorly defined. The aim of this study was to review our experiences of the operative management of metastasis to the pancreas. METHODS: Between 1995 and 2009, 11 patients (8 men and 3 women; median age, 54 years) were admitted to our institution with a metachronously metastatic lesion to the pancreas and later underwent pancreatic resection. The clinical features and outcomes of treatments were examined. RESULTS: The primary cancers were renal cell carcinoma (RCC, n = 7), carcinoid tumor (n = 2), rectal cancer and leiomyosarcoma. Six patients underwent distal pancreatectosplenectomy, 3 pancreaticoduodenectomy and 2 patients underwent enucleation for small RCC. One patient died of metastatic RCC at 53 months after surgery and ten patients remain alive; four patients without disease at 7 to 69 months postoperatively, and the other six with disease at 11 to 68 months. Median postoperative survival of all patients was 34 months. CONCLUSION: Patients with a low surgical risk should be considered for pancreatic metastasectomy if curative resection is possible. Primary cancer type, which is associated with survival benefit, would be the best candidate for surgical resection of metastases to the pancreas. PMID- 22066049 TI - The early and mid-term results of carotid artery stenting in high-risk patients. AB - PURPOSE: This study aimed to investigate early and mid-term outcomes of carotid artery stenting (CAS). METHODS: We retrospectively reviewed 111 patients who were treated for carotid stenosis between October 2004 and December 2009 (42 CASs and 69 carotid endarterectomies [CEAs]). RESULTS: CAS group was older than CEA group (70 years vs. 67 years, P = 0.001). Coronary artery disease and high lesion above the 2nd cervical vertebral body were more common in CAS group (29% vs. 13%, P = 0.002; 4% vs. 24%, P = 0.004). The 30-days stroke rate was higher in CAS group (10% vs. 1% in CEA group, P = 0.067, Fisher's exact test). New brain lesions on diffusion-weighted magnetic resonance imaging were more common in CAS group (48% vs. 20% in CEA group, P = 0.002, chi-square test). The 1-, 3-year freedom from stroke were 91%, 84% in CAS group and 99%, 99% in CEA group (P = 0.007, log-rank test). Univariate analysis showed that female gender and age > 70 years were related with postprocedural neurological complications (P = 0.046 and P = 0.007, log-rank test). However, none were independent risk factors on multivariate analysis. CONCLUSION: In our series, the rates of peri-procedural neurological complications in CAS group were significantly high. These results suggest that more experience and restricted patient selection will be needed for CAS. PMID- 22066050 TI - Association with inflammatory cells and apolipoproteins to the progression of atherosclerosis. AB - PURPOSE: Inflammatory cells are known to be associated with the progression of atherosclerosis and plaque rupture. However, the relation to inflammatory cells and apolipoproteins on the progression of atherosclerosis is unknown. This study was aimed at examining the different expressions of inflammatory cells and evaluate the effect of apolipoprotein (APO) C1 and APO E during the progression of atherosclerosis. METHODS: Ten atherosclerotic tissues were compared with five non-atherosclerotic tissues. The presence of vascular smooth muscle cells (VSMCs), macrophages, T-cells, APO C1, and APO E were identified by Western blotting and immunohistochemical analysis with antibodies. The senescence was analyzed by senescence-associated beta-galactosidase. RESULTS: The protein expression and senescence of macrophages, APO C1 and APO E were significantly higher in the main atherosclerotic lesion than the non-atherosclerotic lesion. A high concentration of inflammatory cells and the paucity of VSMCs were present in the shoulder area. In addition, macrophage and T-cells are expressed in the early stage of atherosclerotic development and more expanded in advanced atherosclerotic plaques. APO C1 was expressed mainly within the necrotic core, and APO E existed mostly around the necrotic core and the fibrous cap in advanced atherosclerotic plaques. CONCLUSION: Our study indicated that the expression and the senescence of macrophage and T-cells may be closelyrelated to induction and deposition of APO C1 and APO E. This contributes to the development and progression of atherosclerotic plaque by expanding the necrotic core. PMID- 22066051 TI - Adrenal ganglioneuroma with hepatic metastasis. AB - Ganglioneuroma is the most differentiated tumor of neural crest origin and rarely arises in the adrenal gland. Ganglioneuroma is typically known to be benign, but very rarely can metastasize to distant sites. We report a case of a 31-year-old man with a huge adrenal mass with hepatic metastases. PMID- 22066052 TI - Clinical significance of morphologic characteristics in triple negative breast cancer. AB - PURPOSE: No clinically useful target molecule has been identified for triple negative (TN) breast cancer, i.e., estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-2-negative phenotype, and its prognosis is poor. The aim of this study is to clarify the clinical and pathologic characteristics of triple negative breast cancer (TNBC). METHODS: The study subjects, 87 women with TNBC, were a subset of patients operated at Kosin University Gospel Hospital from January 2000 to December 2005. We examined pathologic characteristics such as tumor necrosis, infiltrating border, lymphocytic infiltration, prominent nucleoli in TNBC. And we studied the correlation between TNBC and several factors related to pathologic morphology. Chi-squared tests were used for statistical analysis. Kaplan-Meier estimates are presented for the survival function, and differences in survival were analyzed using the log rank test. RESULTS: Tumor necrosis was found in 51 patients (58.3%) in TNBC. And infiltrating border was found in 71 patients (81.0%). Also continuous lymphocytic distribution and prominent nucleoli was found in 31 patients (35.7%), 52 patients (59.7%), respectively. No association was detected between pathologic characteristics and other biological markers. Patients with tumor necrosis positive for TNBC didn't show shorter disease-free survival (P = 0.4490) or overall survival (P = 0.979) than patients without tumor necrosis. CONCLUSION: These findings suggest that pathologic characteristics cannot be used to classify triple-negative breast cancer into only two subtypes with differing prognoses. But because our study is small size study, more abundant patients' dates will be needed to evaluate the morphologic characteristics' predictive role. PMID- 22066053 TI - Experience and analysis of level VII cervical lymph node metastases in patients with papillary thyroid carcinoma. AB - PURPOSE: Papillary thyroid cancer with level VII (anterior superior mediastinal lymph nodes) lymph node metastasis belongs to Stage IV a according to the Americal Joint Committee on Cancer cancer staging. The aim of our study was to identify clinicopathologic factors that are related to level VII cervical lymph node metastasis and to suggest recommendations for level VII dissection. METHODS: We reviewed 195 patients with papillary thyroid carcinoma who had their initial operation containing level VII dissection from April 2006 to June 2007. Level VII dissection involved lymph nodes in the anterior superior mediastinum and tracheoesophageal grooves, extending from the suprasternal notch to the innominate artery. Clinicophathologic factors, such as gender, age and lateral neck metastasis, related to Level VII metastasis were analyzed by tumor size, multifocality of tumor, extrathyroidal extension and lymphovascular invasion. RESULTS: Nine (4.6%) of 195 patients with papillary thyroid carcinoma had level VII metastasis. Clinicopathologic factors that were related to level VII metastasis included lateral neck metastasis (P < 0.01), tumor size (P < 0.01) and lymphovascular invasion (P < 0.05). CONCLUSION: If preoperatively, the tumor size is over 1.5 cm, or there is lateral neck metastasis, level VII dissection must be considered. If there is lymphovascular invasion pathologic findings postoperatively, special attention should be paid for detection of level VII recurrence. PMID- 22066054 TI - Clinical usefulness of laparoscopic total extraperitoneal hernia repair for recurrent inguinal hernia. AB - PURPOSE: Hernia repair after recurrence is a challenging procedure, and many approaches have been suggested for it. Total extraperitoneal (TEP) hernia repair should be considered in recurrent hernia. This study was conducted for the purpose of investigating the clinical usefulness of laparoscopic TEP hernia repair for recurrent inguinal hernia. METHODS: Among the 191 patients who underwent TEP hernia repair at these authors' center from June 2006 to January 2010, the bilateral-hernia cases and the patients with a history of previous pelvic surgery were excluded. A total of 19 patients (12.5%) were enrolled in the recurrent-inguinal-hernia group (group R), and 133 patients (87.5%) in the primary-hernia group (group P). Data were investigated retrospectively, based on the medical records. RESULTS: The mean operation time was 97 minutes in group R and 99 minutes in group P (>0.05). In group R, no operation modality change occurred, and temporary urinary retention was developed in four patients (21.1%). In group P, on the other hand, operation modality change from TEP to the transabdominal preperitoneal approach was necessary in four patients (3%). Additionally, in group P, 30 patients (22.6%) had temporary urinary retention and six (4.5%) had testicular edema. No recurrence was identified during the follow up period in both groups (mean follow-up period: 15.8 months for group R and 18.0 months for group P). CONCLUSION: Laparoscopic TEP hernia repair seems to be a safe and useful method for correcting recurrent inguinal hernia. PMID- 22066055 TI - Laparoscopic totally extraperitoneal repair without suprapubic port: comparison with conventional totally extraperitoneal repair. AB - PURPOSE: We have treated 24 patients through laparoscopic totally extraperitoneal (TEP) repair without suprapubic port by using reliability and reducing the invasiveness of two surgery. This study is aimed to assess the safety and feasibility of the TEP repair without suprapubic port compared to conventional TEP repair. METHODS: From September 2007 to 11 May 2010, we compared two groups that suffer from inguinal hernias. One is comprised of 24 patients who were treated without suprapubic port laparoscopic totally extraperitoneal repair (Group A), and the other is comprised of 100 patients who were treated with conventional laparoscopic totally extraperitoneal repair (Group B). Data regarding patient demographics (sex, age, site of hernia, and the type of hernia), operating time, postoperative hospital stay, the use of analgesics, and complications were prospectively collected. RESULTS: There was no significant difference noted between two groups in relation to sex, age, site, and the type of hernia. The mean operating time and postoperative hospital stay was longer for the Group B (62.9 minutes, 3.55 days) than for the Group A (59.0 minutes, 2.54 days) (P = 0.389, P < 0.001). Postoperative urinary retention, seroma, wound infection were respectively 4.2%, 8.3%, 0% in Group A, and 12.0%, 8.0%, 7% in group B. There was difference between the two groups, but not statistical significance. Group B used more analgesics than Group A (0.33 vs. 0.48), but it wasn't significant statistically (P = 0.234). CONCLUSION: Although prospective randomized studies with long-term follow-up evaluation are needed to confirm our study between laparoscopic totally extraperitoneal repair without suprapubic-port and conventional laparoscopic totally extraperitoneal repair, our method have some advantages in postoperative pain, urinary retention, operating time, postoperative hospital stay, and cosmetic effect. PMID- 22066056 TI - Routine chest computed tomography as a preoperative work-up for primary colorectal cancer: is there any benefit in short-term outcome? AB - PURPOSE: The aim of this study was to assess the role of pre-operative chest computed tomography (CT) compared with abdominopelvic CT (AP-CT) and chest radiography (CXR) for detecting pulmonary metastasis in patients with primary colorectal cancer (CRC). METHODS: We retrospectively analyzed the data of 619 patients with primary CRC who simultaneously received a preoperative chest CT (chest CT group), AP-CT with hilar extension, and CXR (CXR group). RESULTS: In the chest CT group, there were 297 (48.0%) normal, 198 (32%) benign, 96 (15.5%) indeterminate, 26 (4.2%) metastasis, and two lung cancers. Eighteen patients (2.9%) in the CXR group who had no pulmonary metastasis were diagnosed with pulmonary metastasis on a chest CT. The sensitivity and accuracy were 83.9% and 99.0% in the chest CT group, respectively, and 29.0% and 91.5% in the CXR group, respectively (P < 0.0001 and P = 0.0003). CONCLUSION: Chest CT appears to improve the accuracy of pre-operative staging in patients with CRC and is useful for the early detection of pulmonary metastasis as a baseline study for abnormal lung nodules. PMID- 22066057 TI - Lessons learned from 100 initial cases of laparoscopic liver surgery. AB - PURPOSE: Laparoscopic liver resection (LLR) is now widely accepted and is being increasingly performed. The present study describes our experience with LLR at a single center over an eight-year period. METHODS: This retrospective study enrolled 100 patients between October 2002 and February 2010. Forty-six benign lesions and 54 malignant lesions were included. The LLR performed included 58 pure laparoscopy procedures, 18 hand-assisted laparoscopy procedures and 24 hybrid technique procedures. RESULTS: The mean age of the patients was 57 years; among these patients, 31 were over 65 years of age. The mean operation time was 220 minutes. The overall morbidity was 11% and the mortality was zero. Among the 20 patients with simple hepatic cysts, 50% unexpectedly recurred. Among the 41 patients with hepatocellular carcinoma, 21 patients (51%) underwent preoperative radiofrequency ablation therapy or transarterial chemoembolization. During parenchymal-transection, 11 received blood transfusion. The width of the resection margins was under 0.5 cm in 11 cases (27%); 0.5 to 1 cm in 22 cases (54%) and over 1 cm in eight cases (12%). There was no port site seeding, but argon beam coagulation-induced tumor dissemination was observed in two cases. The overall two-year survival rate was 75%. CONCLUSION: This study suggests that the applications for LLR can be gradually expanded when assuring that the safety and curability of LLR are equivalent to that of open liver resection. PMID- 22066058 TI - Characteristic clinical and pathologic features for preoperative diagnosed groove pancreatitis. AB - PURPOSE: Groove pancreatitis is a rare specific form of chronic pancreatitis that extends into the anatomical area between the pancreatic head, the duodenum, and the common bile duct, which are referred to as the groove areas. We present the diagnostic modalities, pathological features and clinical outcomes of a series of symptomatic patients with groove pancreatitis who underwent pancreaticoduodenectomy. METHODS: Six patients undergoing pancreaticoduodenectomy between May 2006 and May 2009 due to a clinical diagnosis of symptomatic groove pancreatitis were retrospectively included in the study. RESULTS: Five cases were male and one case was female, with a median age at diagnosis of 50 years. Their chief complaints were abdominal pain and vomiting. Abdominal computed tomography, endoscopic ultrasound and endoscopic retrograde cholangiopancreatography were performed. Preoperative diagnosis of all patients was groove pancreatitis. Histological finding was compatible with clinically diagnosed groove pancreatitis in five patients and the pathologic diagnosis of the remaining patient was adenocarcinoma of distal common bile duct. Following pancreaticoduodenectomy, four living patients experienced significant pain alleviation. CONCLUSION: The diagnostic imaging modalities of choice for groove pancreatitis are computed tomography and endoscopic ultrasonography. If symptomatic groove pancreatitis is suspected, careful follow-up of patients is necessary and pancreaticoduodenectomy seems to be a reasonable treatment option. PMID- 22066059 TI - Measurement of carotid artery stenosis: correlation analysis between B-mode ultrasonography and contrast arteriography. AB - PURPOSE: To evaluate the efficacy of B-mode ultrasonography (US) in measurement of carotid stenosis% (CS%). METHODS: One hundred and thirth-three carotid arteries in 96 patients who underwent both carotid US and carotid arteriography (CA) were included in this retrospective study. To measure CS% on US, a cross sectional view of the most stenotic segment of the internal carotid artery was captured and residual diameter and original diameter of that segment were measured with electronic caliper on the same plane and in the same direction. To measure CS% on an angiogram, we used European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET) methods. Pearson's correlation analysis and linear regression analysis were used to determine the correlation between CS% on an US and angiogram. RESULTS: Pearson's correlation coefficient (R) between CS% measured in US and CA were 0.853 (ECST method, P < 0.001) and 0.828 (NASCET method, P < 0.001). Accuracies of B-mode US were 93.2%, 88.0%, and 81.2% for estimating CS% by ECST method and 86.5%, 82.7%, and 82% for estimating CS% by NASCET method. CONCLUSION: CS% measured in B-mode US was simpler and showed a strong positive correlation with that measured on an arteriogram either ECST or NASCET method. PMID- 22066060 TI - Home intravenous antibiotic treatment for intractable cholangitis in patients with biliary atresia following Kasai portoenterostomies. AB - PURPOSE: Patients with biliary atresia (BA) treated with Kasai portoenterostomy may later develop intractable cholangitis (IC) that is unresponsive to routine conservative treatment. It may cause biliary cirrhosis and eventually hepatic failure with portal hypertension. Control of IC requires prolonged hospitalization for the administration of intravenous antibiotics. To reduce the hospitalization period, we designed a home intravenous antibiotic treatment (HIVA) which can be administered after initial inpatient treatment. In this study, we reviewed the effects of this treatment. METHODS: We reviewed medical records of 10 patients treated with HIVA for IC after successful Kasai portoenterostomies performed for BA between July 1997 and June 2009. RESULTS: The duration of HIVA ranged from 8 to 39 months (median, 13.5 months). The median length of hospital stay was 5.7 days per month for conventional treatments to manage IC before HIVA and, 1.5 days per month (P = 0.012) after HIVA. The median amount of medical expenses per month was reduced by about one tenth with HIVA. One patient underwent liver transplantation due to uncontrolled esophageal variceal bleeding, but the other nine patients had acceptable hepatic function with native livers. CONCLUSION: HIVA may be an effective primary treatment for IC after Kasai portoenterostomies for BA, and reduce length of hospital stay and medical expense. PMID- 22066061 TI - Hemorrhage from a jejunal polypoid hemangioma: single incisional laparoscopic approach. AB - Bleeding lesions in the small bowel are a much more significant challenge in terms of detection and treatment than those of the stomach or the large bowel, and require extensive gastrointestinal evaluation before a diagnosis can be made. The authors report the case of an 81-year-old female patient who underwent small bowel segmental resection by single incisional laparoscopic approach for distal jejunalhemangioma, which caused severe anemia. An abdominal computed tomography scan demonstrated a highly enhancing polypoid tumor in the distal ileum. During the single incisional laparoscopic exploration using a 2 cm sized skin incision, jejuno-jejunal intussusceptions and a jejunal tumor were noted. Single incisional laparoscopy was performed to assist the jejunal segmental resection. Pathologic reports confirmed the lesion to be a jejunalhemangioma. The authors report an unusual case of jejunalhemangioma caused by intussusception and gastrointestinal hemorrhage, which was treated by single incisional laparoscopic surgery. PMID- 22066062 TI - Isolated primary schwannoma arising on the colon: report of two cases and review of the literature. AB - Primary schwannoma of the large intestine is an extremely rare neoplasm. Here, we report two cases of colonic schwannoma confirmed pathologically after laparoscopic resection. A 52-year-old female and a 59-year-old female were referred by their general practitioners to our coloproctologic clinic for further evaluation and management of colonic submucosal masses. Colonoscopies performed in our institution revealed round submucosal tumors with a smooth and intact mucosa in the mid-ascending and descending colon, respectively. Computed tomography (CT) scans showed an enhancing soft tissue mass measuring 2 * 2 cm in the right colon and well-defined soft tissue nodule measuring 1.5 * 1.7 cm in the proximal descending colon, respectively. We performed laparoscopic right hemicolectomy and segmental left colectomy under the preoperative impression of gastrointestinal stromal tumors. Two cases were both diagnosed to be benign schwannoma of the colon after immunohistochemical stains (S-100 (+), smooth muscle actin (-), CD117 (-), and CD34 (-)). PMID- 22066063 TI - The effective distribution system for the concentration of patients to extra large hospitals. AB - PURPOSE: In Korean society, extra-large hospitals are congested with the majority of patients. Because of the congestions, the urgent patients need to wait anywhere from as short as a month to around three months. These concentrations of the patients on the extra-large hospitals causes not only the economic problem in terms of loss of opportunity cost and resources of other medium and large hospitals but also the fear and the consequential stress of the patients and the families of the patients who are waiting for the surgeries. The phenomenon of the concentrations derived due to the insufficient information to the medical consumers. If the information on medical treatment services such as surgery schedule is provided before the selection of hospital, we expect that the selection of hospital for the patients and their family will differ, resulting in redistribution of concentration phenomenon. In this paper, we propose and verify the effective distribution system for the concentration on the extra-large hospitals. METHODS: Web simulation survey was conducted. A total 100 respondents were divided into 4 groups of 25 respondents and the different information was provided to each group. RESULTS: Through multiple comparisons among groups, only group which was provided with both information about 'the difference of surgical results' and 'the waiting time for surgery', had difference in significance. CONCLUSION: By providing two sets of information to patients, reckless selection of extra-large hospitals can be spread to more appropriate hospitals and therefore achieve effective distribution of the population concentration on extra large hospital. PMID- 22066064 TI - Risk factors for postoperative ileus after urologic laparoscopic surgery. AB - PURPOSE: Although its incidence has decreased with the widespread use of less invasive surgical techniques including laparoscopic surgery, postoperative ileus remains a common postoperative complication. In the field of urologic surgery, with the major exception of radical cystectomy, few studies have focused on postoperative ileus as a complication of laparoscopic surgery. The present study aims to offer further clues in the management of postoperative ileus following urological laparoscopic surgery through an assessment of the associated risk factors. METHODS: The medical records of 267 patients who underwent laparoscopic surgery between February 2004 and November 2009 were reviewed. After excluding cases involving radical cystectomy, combined surgery, open conversion, and severe complications, a total of 249 patients were included for this study. The subjects were divided into a non-ileus group and an ileus group. The gender and age distribution, duration of anesthesia, American Society of Anesthesiologists Physical Status Classification Score, body mass index, degree of operative difficulty, presence of complications, surgical procedure and total opiate dosage were compared between the two groups. RESULTS: Of the 249 patients, 10.8% (n = 27) experienced postoperative ileus. Patients with ileus had a longer duration of anesthesia (P = 0.019), and perioperative complications and blood loss were all correlated with ileus (P = 0.000, 0.004, respectively). Multiple linear regression analysis showed that the modified Clavien classification was an independent risk factor for postoperative ileus (odds ratio, 5.372; 95% confidence interval, 2.084 to 13.845; P = 0.001). CONCLUSION: Postoperative ileus after laparoscopic urologic surgery was more frequent in patients who experienced more perioperative complications. PMID- 22066065 TI - Non-invasive ventilation for surgical patients with acute respiratory failure. AB - PURPOSE: Acute respiratory failure is a relatively common complication in surgical patients, especially after abdominal surgery. Non-invasive ventilation (NIV) is increasingly used in the treatment of acute respiratory failure. We have assessed the usefulness of NIV in surgical patients with acute respiratory failure. METHODS: We retrospectively reviewed the medical charts of patients who were admitted to a surgical intensive care unit between March 2007 and February 2008 with acute respiratory failure. The patients who have got respiratory care for secondary reason such as sepsis and encephalopathy were excluded from this study. RESULTS: Of the 74 patients who were treated with mechanical ventilation, 15 underwent NIV and 59 underwent invasive ventilation. The causes of acute respiratory failure in the NIV group were atelectasis in 5 patients, pneumonia in 5, acute lung injury in 4, and pulmonary edema in 1, this group included 3 patients with acute respiratory failure after extubation. Overall success rate of NIV was 66.7%. CONCLUSION: NIV may be an alternative to conventional ventilation in surgical patients with acute respiratory failure. Use of NIV may avoid re intubation in patients who develop respiratory failure after intubation. PMID- 22066066 TI - Prognostic significance of cytosolic phospholipase A2 expression in patients with colorectal cancer. AB - PURPOSE: Cyclooxygenase-2 is believed to be an important enzyme in the pathogenesis of colorectal cancer (CRC). Cytosolic phospholipase A2 (cPLA2), also, have been suggested to be related to the carcinogenesis of CRC. The aim of this study was to investigate cPLA2 expression and its relationship with prognostic significance in CRC. METHODS: Eighty-eight patients with colorectal cancer who underwent curative surgery were enrolled in this study. cPLA2 was examined in 88 primary CRCs by immunohistochemistry and we compared their expression with clinicopathologic findings, recurrence and survival in patients with CRC. RESULTS: The expression of cPLA2 was positive in 54.5% (48/88). The expression of cPLA2 was not correlated with clinicopathologic parameters. However, cPLA2 expression was significantly related with vascular endothelial growth factor expression. Kaplan-Meier analysis didn't show any clinical significance in disease-free survival and overall survival according to cPLA2 expression. CONCLUSION: These results suggest that cPLA2 expression was not associated with the prognosis of CRC. However, further large-scale studies are needed to clarify the prognostic effect of cPLA2 in CRC. PMID- 22066067 TI - Expression of the survivin-2B splice variant related to the progression of colorectal carcinoma. AB - PURPOSE: Recently, two alternatively spliced survivin variants, survivin-DeltaEx3 and survivin-2B, were identified in a single copy of the survivin gene. It has been reported that the expressions of survivin splice variants significantly correlates with the clinical results in many types of human carcinoma. We investigated the transcription levels of survivin and its splice variants in human colorectal carcinomas, and analyzed correlations between survivin expression levels and clinicopathologic features. METHODS: We used Western blot and real-time quantitative reverse transcription polymerase chain reaction (RT PCR) to analyze the protein and mRNA expression levels of survivin variants in 51 colorectal carcinomas. The quantitative RT-PCR was performed using primer pairs specific for survivin and each of its splice variants, then normalized for the gene that encodes glyceraldehydes-3-phosphate dehydrogenase. RESULTS: In Western blotting, the protein levels of survivin were higher in the tumor tissue than in normal tissue. The expression of survivin, survivin-2B and survivin-DeltaEx3 mRNA was present in 96%, 64.7%, and 82.4% of the samples, respectively. When the pathologic parameters were compared, colorectal cancers of advanced pT stages showed significant decrease in survivin-2B mRNA expression by the quantitative RT PCR (P < 0.001). CONCLUSION: The decreased expression of survivin-2B might be related to tumor progression in colorectal cancers. This finding indicates that alternatively spliced variants of survivin may be involved in refining the functions of survivin during tumor progression. PMID- 22066068 TI - Liver resection for hepatocellular carcinoma: case-matched analysis of laparoscopic versus open resection. AB - PURPOSE: To analyze the outcomes of laparoscopic liver resection compared with open liver resection in patients with hepatocellular carcinoma (HCC). METHODS: Between July 2005 and December 2009, 26 consecutive patients with HCC underwent a pure laparoscopic liver resection, and data from this group (laparoscopic liver resection group, L-group) were compared with a retrospective control group of 29 patients who underwent open liver resection for HCC (open liver resection group, O-group) during the same period. The two groups were matched in terms of demographic data, tumor size, degree of liver cirrhosis, American Society of Anesthesiology score, type of resection, and tumor location. RESULTS: Median operation time and the amount of intraoperative packed red blood cell transfusion in the L-group were 147.5 minutes and 0.35 units, respectively. The L-group revealed a shorter operation time (147.5 vs. 220.0 minutes, P = 0.031) than the O group. No difference in perioperative morbidity or mortality rates was observed (3.8, 0 vs. 24.1%, 0%; P = 0.054, non-specific, respectively); the L-group was associated with a shorter hospital stay than the O-group (11.08 vs. 16.07 days, P = 0.034). After a mean follow-up of 23.9 months (range, 0.7 to 59.4 months), the 1-year disease-free survival rate was 84.6% in the L-group and 82.8% in the O group (P = 0.673). CONCLUSION: Laparoscopic liver resection for HCC is feasible and safe in selected patients and can produce good surgical results with a shorter postoperative hospital stay and similar outcomes in terms of perioperative morbidity, mortality, and disease-free survival than open resection. PMID- 22066069 TI - Inguinal hernia repair in patients with liver cirrhosis accompanied by ascites. AB - PURPOSE: We describe the clinical characteristics and assess the outcomes and stability of inguinal hernia repair under local anesthesia for patients with liver cirrhosis accompanied by ascites. METHODS: We retrospectively reviewed the medical records of 22 patients with cirrhosis and ascites who underwent mesh plug hernia repair performed by a single surgeon from January 2002 to August 2009, and the clinical characteristics and outcomes of the patients were analyzed. RESULTS: Twenty-two patients were included in the study. Fifteen (68.2%) were Child's class B and seven (31.8%) were Child's class C. Hernia repairs were successful without major complications or recurrence in all patients. Minor complications occurred in only three patients, consisting of two hematomas and one case of scrotal swelling. Complications were resolved spontaneously without the need for blood transfusion or reintervention. Thirteen patients died during follow-up (59.1%); eight of these patients died within 1 year after hernia repair. However, there was no 30-day postoperative mortality. Five of the eight patients who died were Child's class B and the remaining three patients were Child's class C. Deaths were all related to cirrhotic complications, and there was no operation related mortality. CONCLUSION: Inguinal hernia repairs under local anesthesia in patients with cirrhosis accompanied by ascites were performed safely and effectively. Therefore, surgical repair is recommended even in patients with refractory ascites and poor hepatic function to prevent life-threatening complications or severe pain and improve quality of life. PMID- 22066070 TI - Laparoscopic total extraperitoneal repair for incarcerated inguinal hernia. AB - PURPOSE: We wanted to measure and compare the patient demographics and perioperative outcomes between patients with incarcerated and patients with non incarcerated inguinal hernia. METHODS: We conducted a retrospective analysis of 945 patients who were scheduled for laparoscopic total extraperitoreal (TEP) repair of inguinal hernia from May 2002 to May 2010. There were 66 patients who had incarcerated hernia and 879 patients who had non-incarcerated hernia. RESULTS: The mean age was younger in the incarcerated hernia group than in the non-incarcerated hernia group (41.67 vs. 48.50 years, P < 0.01), and all the incarcerated inguinal hernias patients were male. Most of the incarcerated hernias (63 out of 66 cases, 95%) were indirect hernias. The mean hospital stay showed no difference between the two groups (1.03 vs. 0.93 days, P = 0.142) but the operation time was longer for the incarcerated group than that for the non incarcerated group (33.36 vs. 24.59 minutes, P < 0.01). Postoperative swelling (including seroma) was more frequent in the incarcerated group (14 out of 66 cases, 21%, P < 0.01), but postoperative pain was similar in both groups (3.0 vs. 8.9%, P = 0.095). There was one recurrence in the non-incarcerated group, but this had no statistical significance. CONCLUSION: Laparoscopic TEP repair for the patients with chronic incarcerated inguinal hernias was safe and feasible. However, a well-designed study is needed to confirm if it is suitable for acute incarcerated inguinal hernias. PMID- 22066071 TI - Clinical experience with persistent cloaca. AB - PURPOSE: Persistent cloaca is one of the most severe types of anorectal malformation. Appropriate initial drainage is difficult due to their various malformations and hydrocolpos or dilated urinary bladder. Corrective surgery also differs among individual patients. We describe our experiences with the surgical management of children with persistent cloaca. METHODS: We retrospectively reviewed 16 children diagnosed with persistent cloaca at Asan Medical Center. RESULTS: Sixteen patients were managed in their neonatal period. Twelve patients had enlarged bladder or vagina at birth. Three patients, who did not undergo cystostomy or vaginostomy at first operation, had earlier complications after surgery or required drainage tube insertion. One patient who did not undergo hydrocolpos drainage died of sepsis and complications. Nine patients underwent corrective surgery; posterior sagittal anorectovaginourethroplasty using the Pena method. Three patients required additional operations due to complications after surgery. CONCLUSION: Patients found to have anatomical malformations before colostomy, as well as hydrocolpos and bladder enlargement, require a vaginostomy with or without a cystostomy to reduce complications. Follow-up is required in patients with hydrocolpos and bladder enlargement to determine whether vaginal drainage improves dilated bladder. Continuous long-term follow-up examination is required to determine the long-term results of corrective surgery. PMID- 22066072 TI - Round ligament varicosities mimicking inguinal hernia in pregnancy. AB - Round ligament varicosities during pregnancy are rare, and can easily be mistaken for an inguinal hernia. On physical examination, round ligament varicosities and groin hernia are difficult to distinguish. The diagnosis of round ligament varicosities can be established on gray-scale and color Doppler sonography. We experienced a case of round ligament varicosities in which a 29-year-old woman presented symptoms at 36 weeks gestation. The patient was diagnosed using Doppler sonography, managed with conservative therapy, and had an uncomplicated vaginal delivery at 40 weeks. The symptoms were resolved completely by two weeks postpartum. We report a case of round ligament varicosities that was diagnosed at 36 weeks of gestation with a review of the literature. PMID- 22066073 TI - Hepatoid adenocarcinoma of the gallbladder with production of alpha-fetoprotein. AB - Hepatoid adenocarcinoma (HAC) is a tumor with aberrant hepatocellular differentiation that occurs in extrahepatic organs. HAC of the gallbladder is rare, and cases of alpha-fetoprotein production are extremely rare. A 61-year-old man was diagnosed with gallbladder adenocarcinoma after laparoscopic cholecystectomy. A radical operation including resection of liver bed and lymph node dissection was performed, and no tumor cell was found. However, at postoperative 19 months, he showed lymphadenopathy of the portocaval area and tumor thrombi in the right portal vein with high levels of serum alpha fetoprotein. After right hemihepatectomy and portahepatis lymph node dissection was performed, he was diagnosed with metastatic HAC. On reviewing the gallbladder specimen, the tumor finally demonstrated HAC as the primary origin. Despite adjuvant therapy, the patient died from multiple liver metastasis 26 months after cholecystectomy. Although HAC of the gallbladder is a very rare malignancy, awareness of its existence is critical to avoid misdiagnosis. PMID- 22066074 TI - Laparoscopy-assisted distal gastrectomy for gastric cancer after liver transplantation. AB - A case report described a 72-year-old man with a history of a deceased-donor liver transplantation (due to hepatitis B-associated end-stage liver cirrhosis) performed in 1994. The patient was diagnosed with renal cell carcinoma and pulmonary metastasis in 1997 and was successfully treated with radiofrequency ablation and thoracoscopic superior segmentectomy. There was no evidence of newly diagnosed metastatic lesions or recurrence until the 19th post-operative month. Gastric cancer was identified by endoscopy during a routine follow-up examination; the pre-pyloric antral lesion measured 1.5 cm in size and was histologically well-differentiated and confined to the submucosal layers on endoscopic ultrasound. Laparoscopic gastrectomy and lymph node dissection (D1 + beta) was successfully performed in March 2009, and the patient was discharged on the 5th post-operative day without complications. This suggests that laparoscopic surgery is one of the feasible methods for resection of gastric cancer in liver transplant patients. PMID- 22066075 TI - Segmental duodenectomy with duodenojejunostomy of gastrointestinal stromal tumor involving the duodenum. AB - Duodenal gastrointestinal stromal tumors (GISTs) are uncommon and a relatively small subset of GISTs whose optimal surgical procedure has not been well defined. Because submucosal spread and local lymph node involvement is infrequent in GISTs, wide margins with routine lymph node dissection may not be required. Various techniques of limited resection for duodenal GISTs have been described depending on the site and the size of the tumors. In this study, we report two cases of GIST involving the third and fourth portion of the duodenum successfully treated by segmental duodenectomy with end-to-end duodenojejunostomy. This technique should be considered as a treatment option for GIST located at the third and fourth portion of the duodenum. PMID- 22066076 TI - Pneumomediastinum caused by colonic diverticulitis perforation. AB - A 59-year-old man presented with abdominal and left flank pain. The symptom had started 30 days before as an acute nephrolithiasis, which had worsened despite conservative management. The abdomen was slightly distended and tender over the lower abdomen, without signs of generalized peritoneal irritation. A computed tomography (CT) scan showed an abscess in left para-renal space up to the subphrenic space and an unexpected pneumomediastinum. An emergency operation was performed, which showed retroperitoneal diverticulitis perforation of the sigmoid descending junction with abscess formation. A segmental resection of the diseased colon and end-colostomy was performed (Hartmann's procedure). However, the patient's condition progressively deteriorated, and he died of sepsis and multi organ failure on the 5th postoperative day. Although pneumomediastinum caused by colonic diverticulitis perforation is extremely rare, it could be a life threatening condition in patients without signs of peritonitis because of delayed diagnosis. PMID- 22066077 TI - Laparoscopic resection of a appendiceal mucocele. AB - Laparoscopic resection of appendiceal mucoceles has recently been described, but the safety and efficacy are controversial. We present two cases of laparoscopic mucocelectomies involving 14 and 15 cm cystic masses originating from the appendix. The laparoscopic mucocelectomies were performed using four ports. From the beginning of the procedure, a laparoscopic bag was used to safely contain the mucocele, prevent rupture of the mucocele, and retract the mucocele. An endoscopic stapling device was used to transect the base of the cecum. Minimal handling was achieved by gravity and with the use of laparoscopic instruments. Laparoscopic appendectomies are widely performed for acute appendicitis, but laparoscopic resection is not routinely performed for an appendiceal mucocele because of the risk of perforation and subsequent pseudomyxoma peritonei. We report two cases of laparoscopic appendiceal mucocelectomies, which were performed safely with laparoscopic instruments and minimal manipulation. PMID- 22066078 TI - Sarcomatoid carcinoma of colon: extremely poor prognosis. AB - Colonic sarcomatoid carcinomas are known to be extremely rare tumors, with only 22 cases reported either as sarcomatoid carcinomas or carcinosarcomas in the literature. The known characteristics are rapid growth, a high recurrence rate, and an extremely poor prognosis. Herein we report a case of a patient who had a sarcomatoid carcinoma of the sigmoid colon and died only 22 days after surgery due to rapid tumor growth. PMID- 22066079 TI - Primary adenosquamous carcinoma of the colon. AB - Adenosquamous cell carcinoma (Ad-SCC) of the colon is rare. The pathogenesis of Ad-SCC is unclear, however, several hypotheses have been suggested. The clinical presentation and gross findings of Ad-SCC of the colon are similar to those of adenocarcinoma of the colon, but Ad-SCC has a more aggressive clinical course and a poorer prognosis. We report on two cases of Ad-SCC of the colon with obstruction; a collision-type Ad-SCC that has not only obstruction but also numerous hepatic metastases, and a composite-type Ad-SCC treated with left hemicolectomy followed by an adjuvant chemotherapy. PMID- 22066080 TI - Graft-versus-host disease after kidney transplantation. AB - Graft-versus-host disease (GVHD) is a rare complication after kidney transplantation. We describe a 62-year-old female with end-stage renal disease due to hypertension. She received a kidney with 4 mismatched human leukocyte antigen (HLA) out of 6 HLA - A, B, DR from a deceased donor. After the procedure, the patient showed watery diarrhea on postoperative day (POD) 45. An endoscopic biopsy of the colon revealed some apoptotic cells consistent with GVHD. Thrombocytopenia was gradually developed on POD 54. She received steroid pulse therapy, and thrombocytopenia did not progress. However, pneumonia, renal failure, and cardiac failure occurred. She died due to multiple organ failure. We must consider GVHD in renal transplant recipients without homozygous or identical HLA, who had only watery diarrhea without other typical GVHD symptoms such as skin rash and fever, although GVHD is rare in renal transplant recipients. PMID- 22066081 TI - Cardiac tamponade caused by tuberculosis pericarditis in renal transplant recipients. AB - A 50-year-old male, renal transplant recipient, was admitted with fever and chest discomfort. At admission, chest radiologic finding was negative and echocardiography showed minimal pericardial effusion. After 2 days of admission, chest pain worsened and blood pressure fell to 60/40 mmHg. Emergency echocardiography showed a large amount of pericardial effusion compressing the entire heart. Pericardiocentesis was performed immediately. Mycobacterium tuberculosis was isolated from pericardial fluid. Tuberculosis pericarditis should be considered as the cause of cardiac tamponade in renal transplant recipients, even with the absence of pericardial effusion in the initial study or suggestive history. PMID- 22066082 TI - A giant retroperitoneal lymphangioma in a patient with neurofibromatosis type 1. AB - Neurofibromatosis type 1 (NF-1) is a genetically inherited disorder that may cause skin abnormalities and tumors that form on nerve tissues. These tumors can be small or large and can occur anywhere in the body, including the brain, spinal cord, or other peripheral nerves. Retroperitoneal lymphangiomas are very rare benign malformations of the lymphatic system. About 95% lymphangiomas occur in the skin and the subcutaneous tissues of the head, neck and axillary region and the remaining 5% appear in other parts of the body such as lungs, pleura, pericardium, liver, gallbladder, kidney, and the mesentery. Herein, we report the case of a giant retroperitoneal lymphangioma in a patient with NF-1 with a review of the literature. PMID- 22066083 TI - Pneumatosis intestinalis after adult liver transplantation. AB - Pneumatosis intestinalis is an uncommon disorder characterized by an accumulation of gas in the bowel wall. We described three cases undertaking liver transplantation. The patients developed diarrhea in three cases and high fever in two. An abdominal X-ray and computed tomography scan demonstrated extensive pneumatosis intestinalis in the colon with pneumoperitoneum mimicking hollow organ perforation. However, the patients had no abdominal symptoms and there was no evidence of peritonitis. The infection work-up was negative except one case with cytomegalovirus antigenemia. After one week of conservative management including bowel rest and antibiotic therapy, their pneumoperitoneum resolved spontaneously without any complication. Pneumatosis intestinalis should be considered as a differential diagnosis after adult liver transplantation with patients suffering from watery diarrhea and fever. Pneumoperitoneum, air-density in mesentery and retroperitoneum in patients with pneumatosis intestinalis without signs of peritonitis improved with conservative management, which included bowel rest and antibiotic therapy. PMID- 22066084 TI - Auxiliary partial orthotopic liver transplantation for adult onset type II citrullinemia. AB - Adult-onset type II citrullinemia (CTLN2) is a disorder caused by an inborn error of metabolism affecting the liver. CTLN2 is an autosomal recessive disorder characterized by recurrent encephalopathy with hyperammonemia due to highly elevated plasma levels of citrulline and ammonia, caused by a deficiency of argininosuccinate synthetase in the liver. A small number of patients have undergone liver transplantation with favorable results. In Korea, the limitations of the deceased donor pool have made living donor liver transplantation a common alternative treatment option. We report the case of a patient with type II citrullinemia who was treated successfully with auxiliary partial orthotopic liver transplantation (APOLT) from a living donor. This is the first description of an APOLT for a patient with adult onset type II citrullinemia in Korea. PMID- 22066085 TI - Cystic lymphangioma of the pancreas mimicking pancreatic pseudocyst. AB - Lymphangiomas are rare congenital benign tumors arising from the lymphatic system, and are mostly encountered in the neck and axillary regions of pediatric patients (95%). Lymphangioma of the pancreas is extremely rare accounting for less than 1% of these tumors. We report here on a case of pancreatic cystic lymphangioma. A 54-year-old woman presented with intermittent postprandial abdominal discomfort and radiating back pain. Abdominal computed tomography scan revealed 8 * 6.5 cm hypodense cystic mass arising from the tail of the pancreas without septa or solid component. The initial impression was a pancreatic pseudocyst. The patient underwent distal pancreatectomy with splenectomy. The histopathologic and immunohistochemical study helped make the diagnosis of a pancreatic cystic lymphangioma. Herein, we report a case of pancreatic cystic lymphangioma mimicking pancreatic pseudocyst and review the relevant medical literature. PMID- 22066086 TI - Laparoscopic splenectomy for sclerosing angiomatoid nodular transformation of the spleen. AB - Primary splenic tumors are rare and mainly found incidentally on radiologic studies. Among them, sclerosing angiomatoid nodular transformation (SANT) of the spleen is a new entity defined as a benign pathologic lesion. Most SANTs have no clinical symptoms and are occasionally accompanied by other splenic diseases such as malignancies. So, the exact diagnosis of the nature of the splenic tumor is mandatory for further treatment. But, preoperative diagnosis is not easy since it is difficult to obtain the tissue from the spleen for pathological study. Recently, laparoscopic splenectomy has become the more standard procedure for the spleen for diagnosis and treatment. Here, we report a rare case of SANT diagnosed following laparoscopic splenectomy. PMID- 22066087 TI - Early gastric cancer arising from heterotopic gastric mucosa in the gastric submucosa. AB - The incidence of heterotopic gastric mucosa located in the submucosa in resected stomach specimens has been reported to be 3.0 to 20.1%. Heterotopic gastric mucosa is thought to be a benign disease, which rarely becomes malignant. Heterotopic gastric mucosa exists in the gastric submucosa, and gastric cancer rarely occurs in heterotopic gastric mucosa. Since tumors are located in the normal submucosa, they appear as submucosal tumors during endoscopy, and are diagnosed through endoscopic biopsies with some difficulty. For such reasons, heterotopic gastric mucosa is mistaken as gastric submucosal tumor. Recently, two cases of early gastric cancer arising from heterotopic gastric mucosa in the gastric submucosa were treated. Both cases were diagnosed as submucosal tumors based on upper gastrointestinal endoscopy, endoscopic ultrasound, and computed tomography findings, and in both cases, laparoscopic wedge resections were performed, the surgical findings of which also suggested submucosal tumors. However, pathologic assessment of the surgical specimens led to the diagnosis of well-differentiated intramucosal adenocarcinoma arising from heterotopic gastric mucosa in the gastric submucosa. PMID- 22066088 TI - Components separation technique for large abdominal wall defect. AB - Repairing large incisional hernia with abdominal wall reconstruction is a technically challenging problem for surgeons. We report our experience of large midline incisional hernia which was repaired successfully with components separation technique. A patient with incisional hernia, 35 * 20 cm in size, underwent operation following standard components separation technique. The aponeurosis of the external abdominal oblique muscle was longitudinally transected from the rectus sheath, and the external abdominal oblique muscle was separated from the internal abdominal oblique muscle. With further separation of the posterior rectus sheath from the rectus abdominis muscle, closure of the abdominal wall was attained without tension. The post-operative course was uneventful with minor wound seroma. The patient discharged safely, and no further complication in terms of recurrence and wound problem has occurred. Components separation technique could be a possible and effective treatment option for repair of large abdominal wall defect. PMID- 22066089 TI - Experience of non-vascular complications following endovascular aneurysm repair for abdominal aortic aneurysm. AB - Endovascular aneurysm repair (EVAR) for the treatment of abdominal aortic aneurysm (AAA) is a widely used method, and its decreased invasiveness compared to traditional surgical repair has brought about reduced rates of morbidity and mortality. Several vascular complications related to the procedure have been reported, but non-vascular complications have rarely occurred. We report herein the case of a 78-year-old man who underwent EVAR for AAA and presented with active duodenal ulcer bleeding and acute acalculous cholecystitis as complications after the procedure. We must consider that a wide spectrum of complications may occur following EVAR, and therefore it is important to evaluate the risks of complication and to take the necessary measures to minimize them. PMID- 22066090 TI - Pseudoaneurysm of the popliteal artery mimicking tumorous condition. AB - Diagnosing pseudoaneurysms of the popliteal artery is usually straightforward in physical examinations and imaging findings. However, when a pseudoaneurysm shows a soft tissue mass with adjacent osseous change, it can mimic a bone tumor or a soft tissue sarcoma. We present a case of a 65-year-old man who had a pseudoaneurysm of the popliteal artery showing soft tissue mass and insinuating into the intramedullary cavity of the tibia. This presented case emphasizes the importance of considering pseudoaneurysms in the differential diagnosis of an apparent soft tissue mass with pressure erosion in adjacent bone. PMID- 22066091 TI - Adventitial cystic disease of common femoral vein. AB - Adventitial cystic disease (ACD) of venous system is an extremely rare condition. Very few reports of ACD in venous system have been described. In this report we discuss two cases of common femoral vein ACD that presented with a swollen leg by the obstruction of the vein. Ultrasound imaging showed the typical hypoechoic fluid filled cyst with a posterior acoustic window. Computed tomography scan and ascending venogram showed a stenosis to flow in the common femoral vein caused by an extrinsic mass. Trans-adventitial evacuation of cyst with removal of vein wall was performed for both cases. During operation we found the gelatinous material in the cysts arising in the wall of the common femoral vein and compressing the lumen. The patients were released after short hospitalization and have remained symptom free with no recurrence. PMID- 22066092 TI - Desmoplastic small round cell tumor of the stomach mimicking a gastric cancer in a child. AB - Intra-abdominal desmoplastic small round cell tumor (DSRCT) is a highly malignant tumor of uncertain histogenesis. Here we report a case of DSRCT involving the stomach, initially misdiagnosed as gastric cancer. A 12-year-old boy presented with upper abdominal pain developed 1 month prior. On gastroscopy, a 7-cm mass was noted involving the esophago-gastric junction to the fundus, and positron emission tomography showed multiple hot uptakes suggesting distant metastasis. Gastroscopic biopsy showed poorly differentiated malignant cells. We diagnosed as stage IV gastric cancer and treated with 6 cycles of chemotherapy. Laparotomy revealed a huge gastric mass along with peritoneal disseminations. Palliative proximal gastrectomy was performed. Pathological examination revealed transmural involvement of DSRCT, and t(11;22)(p12;q12) was demonstrated on fluorescence in situ hybridization test. The chemotherapeutic regimen was changed and the patient underwent 8 additional cycles of post-operative chemotherapy. The patient is now alive and the residual tumor shows no significant changes after chemotherapy. PMID- 22066093 TI - Primary segmental volvulus of the ileum mimicking meconium plug syndrome. AB - Primary segmental volvulus (PSV) of the ileum in neonate occurs rarely but shows an aggressive clinical course. Thus, early diagnosis is important to prevent necrosis and perforation of the intestine. We report a case of PSV of the ileum in a 2-day-old female neonate whose clinical features and radiologic findings appeared to be meconium plug syndrome. PMID- 22066094 TI - Investigation of relationship between inhalation injury assessment and prognosis in burn patients. AB - PURPOSE: Inhalation injury is one of the most severe morbidity and mortality factors in burn patients. The purpose of this study is to analyze the impact of inhalation injury to the prognosis of burn patients and to investigate the relationship between the inhalation injury assessment and the prognosis of patients. METHODS: Bronchoscopy was performed in 170 patients who had the suspicion of inhalation injury and the patients were reviewed retrospectively from January 2008 to December 2009. Mortality was compared between the factors of brochoscopic findings, age, total body surface area (TBSA) burned, carboxyhemoglobin (COHb) level, PaO(2)/FiO(2) (P/F) ratio. RESULTS: Of 170 patients, 28 patients had no inhalation bronchoscopic finding. 109 patients had mild inhalation, 31 patients had moderate inhalation, only 2 patients had severe inhalation findings. The patients of moderate and severe inhalation findings had higher mortality (48.5%) than mild inhalation patients (31.1%). The larger total burnsurface area in inhalation patients, the greater the mortality. When compared to total admitted burn patients during the same period, inhalation patients showed higher mortality in the patients between 10 to 40% total burn surface area. Inhalation patients whose P/F ratio was below 300 showed higher mortality than above 300. But inhalation patients whose COHb level was below 1.5 had no difference in mortality with patients above 1.5. The COHb level and P/F ratio was the statistically different factors between inhalation patients and non inhalation group in the mortality. CONCLUSION: Bronchoscopic findings, age, TBSA burned, P/F ratio were related with mortality in inhalation patients. When the international standardization of bronchoscopic classification developed, it can be possible to assess the inhalation patients more objectively and that will lead to the advancement in inhalation treatment and research. PMID- 22066095 TI - Short-term results of ABO-incompatible living donor kidney transplantation: comparison with ABO-compatible grafts. AB - PURPOSE: ABO incompatible (ABOi) kidney transplantation (KT) has been increasing to compensate for the shortage of organ donors. However, detailed comparative analyses of ABOi KT with ABO compatible (ABOc) KT are still rare. METHODS: This retrospective study compared 12 consecutive ABOi KTs to 50 ABOc KTs that employed the same maintenance immunosuppressive agents during the same period. Comparisons of patient survival, graft survival, graft function, and complications were made until post-transplant day 90. RESULTS: Baseline characteristics of the two groups were similar except for the positivity of panel reactive antibody (12% in the ABOc group vs. 42% in the ABOi group; P = 0.029). There were no significant differences in patient survival, graft survival, post-operative renal function, incidence of acute rejection, infections, or medical and surgical complications. However, bleeding complications were more common in the ABOi group (25%) than versus the ABOc group (6%) (P = 0.08). The preoperative and total hospital stay of the ABOi patients was significantly longer than the ABOc patients (P = 0.001). CONCLUSION: ABOi KT is a viable and safe option for patients whose only donor is blood incompatible, despite the longer preoperative hospital stay for preparation. PMID- 22066096 TI - Clinicopathologic characteristics of serosa-positive gastric carcinoma in elderly patients. AB - PURPOSE: The relationship between the prognosis and the age of patients with gastric carcinoma is controversial. This study examined the clinicopathologic features of elderly gastric carcinoma patients with serosal invasion. METHODS: We reviewed the hospital records of 136 elderly gastric carcinoma patients with serosal invasion retrospectively to compare the clinicopathologic findings in the elderly (aged > 70 years) and young (aged < 36 years). RESULTS: The 5-year survival rates of elderly and young patients with curative resection did not differ statistically (33.9% vs. 43.3%; P = 0.318). Multivariate analysis showed that two factors were independent, statistically significant parameters associated with survival: histologic type (risk ratio, 1.805; 95% confidence interval [CI], 1.041 to 3.132; P < 0.05) and operative curability (risk ratio, 2.506; 95% CI, 1.371 to 4.581; P < 0.01). CONCLUSION: This study demonstrated that elderly gastric carcinoma patients with serosal invasion do not have a worse prognosis than young patients. The important prognostic factor was whether the patients underwent curative resection. PMID- 22066097 TI - Comparative analysis of radiofrequency ablation and surgical resection for colorectal liver metastases. AB - PURPOSE: To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection for the treatment of colorectal liver metastasis (CRLM). METHODS: Between 1996 and 2008, 177 patients underwent RFA, 278 underwent hepatic resection and 27 underwent combination therapy for CRLM. Comparative analysis of clinical outcomes was performed including number of liver metastases, tumor size, and time of CRLM. RESULTS: Based on multivariate analysis, overall survival (OS) correlated with the number of liver metastases and the use of combined chemotherapy (P < 0.001, respectively). Disease-free survival (DFS) also correlated with the number of liver metastases (P < 0.001). In the 226 patients with solitary CRLM < 3 cm, OS and DFS rates did not differ between the RFA group and the resection group (P = 0.962 and P = 0.980). In the 70 patients with solitary CRLM >= 3 cm, DFS was significantly lower in the RFA group as compared with the resection group (P = 0.015). CONCLUSION: The results indicate that RFA may be a safe alternative treatment for solitary CRLM less than 3 cm, with outcomes equivalent to those achieved with hepatic resection. A randomized controlled study comparing RFA and resection for patients with single small metastasis would help to determine the most efficient treatment modalities for CRLM. PMID- 22066098 TI - An early single-center experience of portal vein thrombosis in living donor liver transplantation: clinical feature, management and outcome. AB - PURPOSE: Portal vein thrombosis (PVT) has been considered a relative contraindication for living donor liver transplantation (LDLT). However, it is no longer a contraindication of LDLT due to improvement in surgical techniques and approaches to PVT. The aim of this study was to assess the impact of PVT on outcomes in LDLT patients. METHODS: We retrospectively analyzed the data from 97 adult patients undergoing LDLT in our center from July 2008 to June 2010. Intraoperative findings and preoperative imaging results were reviewed for PVT grading (Yerdel grading). We analyzed the technical aspects and comparisons of risk factors, perioperative variables, and survivals between patients with and without PVT based on the grades. RESULTS: In the 97 LDLT patients, 18 patients were confirmed to have PVT (18.5%) including grade I cases (n = 8), grade II (n = 7), and grade III (n = 3). Prior treatment of portal hypertension was found to be an independent risk factor for PVT (P = 0.001). The comparisons between PVT and no PVT groups showed no significant difference in intraoperative and postoperative variables except for postoperative bleeding (P = 0.036). The short term portal vein patency, in-hospital mortality and survival rates were not significantly different between the PVT and control groups. CONCLUSION: The outcomes are similar to non-PVT group in terms of in-hospital mortality, survival rates, and postoperative complications. Therefore, our study suggests that PVT cannot be considered to be a contraindication for LDLT and LDLT could be undertaken without increased morbidity and mortality in patients with PVT, in spite of operative complexity. PMID- 22066099 TI - Hybrid surgery versus percutaneous mechanical thrombectomy for the thrombosed hemodialysis autogenous arteriovenous fistulas. AB - PURPOSE: For the successful treatment of thrombosed autogenous arteriovenous fistula (AVF), we designed and performed a hybrid surgery. Its clinical outcomes were compared with those of percutaneous mechanical thrombectomy, retrospectively. METHODS: Forty cases of thrombosed autogenous AVFs underwent hybrid surgery, whereas 19 cases received percutaneous mechanical thrombectomy. Hybrid surgery consisted of surgical thrombectomy, balloon angioplasty and/or additional surgical angioplasty. Percutaneous mechanical thrombectomy included catheter-introduced thrombus aspiration, balloon angioplasty and/or stenting. Procedure related outcomes such as technical success rates and primary patency rates were analyzed, retrospectively. RESULTS: There were no statistically significant differences between the two groups in terms of demographic data of the patients including age, gender, diabetes status, and frequency of antiplatelet use, as well as the characteristics of thrombosed autogenous AVFs such as access age, site, type, and length of time between thrombosis and AVF creation (P > 0.05). Technical success rates (92.5% vs. 68.4%, P = 0.005, respectively) and primary patency rates (85.9% vs. 36.8% at 6 months, 81.1% vs. 26.3% at 12 months, 81.1% vs.21.1% at 18 and 24 months respectively, log-rank test, (P < 0.001) were significantly higher in the hybrid surgery group. In terms of cost analysis, supply cost was not different (P = 0.065), but total cost was statistically lower in the hybrid surgery group (P = 0.019). CONCLUSION: Hybrid surgery showed better technical success rates and patency rates in the salvaging of thrombosed autogenous AVFs than in percutaneous mechanical thrombectomy. PMID- 22066100 TI - One surgeon experiences in childhood inguinal hernias. AB - PURPOSE: In this manuscript we report one pediatric surgeon's experience in childhood inguinal hernia repair. METHODS: From 2005 to 2008, 402 children with inguinal hernias were operated on by one surgeon. A retrospective survey of their charts was carried out to evaluate the demographics and clinical aspects of these patients. RESULTS: The ages ranged from 20 days to 16 years with a male-to-female ratio of 2.5:1. 64.9% right, 27.1% left, and 7.9% bilateral hernias. Hydroceles were present in 6.2% assosiated hernias. Incarceration occurred in 8.7% of children. An opposite-side hernia developed in 5.7%. 5.3 percent of patients with a hernia repair on the right side later developed a hernia on the left side, and 8.2% of patients with a hernia repair on the left side later developed one on the right side. 4.5 percent of all male patients in this series and 8.6% of female patients developed an opposite-side hernia. While overall recurrence rate was 1.2%, our recurrence rate was 0.25%. There was a 0.24% wound infection rate, and 1 (0.24%) testicle was atrophic at follow-up. CONCLUSION: In this study, in the recurrence of childhood hernia, the general surgeon's intervention was the prominent cause. It is suggested by the study that inguinal hernias on the contralateral side becomes symptomatic within the first six months following initial operation.Therefor, close observation is needed in that time. PMID- 22066101 TI - The impact of the prenatal ultrasonography on birth of babies with Korean pediatric surgical index diseases. AB - PURPOSE: The purpose of this study is to examine the impact of prenatal ultrasonography (US) on the birth of babies with diseases listed on the Korean pediatric surgery index diseases (IDs). METHODS: Depending the ease of diagnosis using prenatal US, [diagnostic facility if prenatal US] IDs were divided into easily diagnosed (ED), not easily diagnosed (NED) and detected with difficulty (DD) groups. Five-year data were obtained for the total live birth number (TBN) from the Korean Statistical Information Service, and the actual birth number of IDs (ABNID) from the Korean Health Insurance Review and Assessment Service. The certified incidences of IDs (I) were obtained from a prestigious textbook of pediatric surgery. The estimated abortion rate (AR) of fetus in each group was obtained using the following formula: AR (%) = [1 - (ABNID)/(TBN * I)] * 100. RESULTS: The AR with all IDs was 38 to 77%. The AR was 78 to 93% for ED group, 38 to 66% for NED group and 0% for DD group. CONCLUSION: In spite of high survival rates after treatment, the AR of each group depends on the ease of diagnosis using prenatal US in Korea. A recommendatory policy for the fetus with IDs should be urgently established after general consensus within the related medical societies. PMID- 22066102 TI - Fibrous hamartoma of infancy: an experience of a single institute. AB - PURPOSE: Fibrous hamartoma (FH) of infancy is a distinctive fibrous growth that most frequently occurs at birth and during the postnatal period. It is important for clinicians and pathologists to recognize this entity to avoid an aggressive approach. METHODS: We herein describe the clinicopathologic features of 9 FHs diagnosed at a single institution between 1997 and 2010. RESULTS: There were 7 boys and 2 girls, and the mean age of presentation was 14.7 months. The common locations were the lower back and gluteal region (n = 3) and scrotum (n = 2). They were solitary lesions, and measured 1.0 to 7.0 cm in maximum diameter (mean, 4.9 cm). The excised masses tended to be poorly circumscribed, and consisted of an intimate mixture of firm, gray-white tissue with fat. Histologically, these lesions were composed of 3 components forming a vague, irregular, organoid pattern: well-defined intersecting trabeculae of fibrocollagenous tissue; loosely textured areas of small, rounded, primitive mesenchymal cells; and mature fat. Over a median follow-up of 72 months, no patient showed recurrence. CONCLUSION: FH should be distinguished from other forms of fibromatosis and malignant tumors because it is benign and usually cured by local excision. PMID- 22066103 TI - Melanosis ilei induced by prolonged charcoal ingestion. AB - Gastrointestinal melanosis is observed most frequently in the colon it also can develop in the ileum, duodenum and esophagus very rarely. Melanosis ilei was thought that causative materials such as aluminum, magnesium, silicate, titanium and other compounds entered the body through the ingestion of agents. We experienced a case of melanosis in the terminal ileum that a 65-year-old female patient ingested 10 g edible charcoal everyday for 3 years to address symptoms of chronic abdominal pain. In Korea, edible charcoal has been considered to be an effective folk remedy for patients with diarrhea or chronic abdominal pain. In our case, a follow up colonoscopy was performed 3.5 years after the termination of the ingestion of edible charcoal, at which point pigmentation was faded color intensity. In conclusion, it is thought that melanosis ilei is a rare disease by ingestion of causative materials and is discontinuous, local and reversible disease. PMID- 22066104 TI - Synchronous granular cell tumors in the perianus and chest wall. AB - Granular cell tumor (GCT) is a rare tumor that originates from the Schwann cells in the skin, soft tissues, and internal organs. Usually, GCTs are clinically benign, although malignant and multifocal forms are very rarely known to occur. Cases of GCT of the perianus are rare, and thus far, no study has reported synchronous GCTs of the perianus and the chest wall. We report a case of a 31 year-old woman with synchronous GCTs of the perianus and the chest wall to have a mind of consideration of the possibility of GCT in the differential diagnosis of perianal tumor. PMID- 22066105 TI - Review of atypical cytology of thyroid nodule according to the Bethesda system and its beneficial effect in the surgical treatment of papillary carcinoma. AB - PURPOSE: For the atypical cases of fine needle aspiration (FNA) cytology of thyroid nodules, ultrasonographic findings are a primary guideline for the surgical treatment. However, they have the intrinsic risk of overtreatment, as well. In this study we examined whether the Bethesda system could provide a real effect on the diagnostic rate of atypical cytology, and thereby reduce the number of cases diagnosed as atypical from FNA cytology. METHODS: We reviewed 166 cases diagnosed as atypical by FNA cytology at this institute between the years 2005 to 2010. We classified these cases on the basis of ultrasonographic and cytological findings and compared them with the histological results. RESULTS: Ultrasonographically, findings suspicious for malignancy and indeterminate were associated with 83.7% and 47.2% of malignancy rates, respectively. Cytopathologically, the malignancy rates varied according to the main cytological features and the highest malignancy rate was 77.3%. Based on the Bethesda system, 39.2% of the cases diagnosed as atypical could be grouped into the category of suspicious for malignancy and yielded a malignancy rate of 76.9%. CONCLUSION: Although ultrasonography provides an excellent guideline for the surgical treatment of atypical cases, it also showed considerable risk of overtreatment. The Bethesda system did not offer definitive effects on the rate of atypical cytology, but this system seemed to provide stricter boundaries for the atypical cytology and to aid in reducing the rates thereof. This in turn may permit that more limited cases are allotted to ultrasonographic decision making. PMID- 22066106 TI - Induction of apoptosis with diallyl disulfide in AGS gastric cancer cell line. AB - PURPOSE: Diallyl disulfide (DADS) is a major organosulfur compound derived from garlic. It has been reported that DADS is able to inhibit the proliferation of several tumor cells. In this study, the effect of DADS was investigated in terms of the proliferation of AGS, gastric adenocarcinoma cell line at various concentrations. METHODS: The viability of cultured cells was determined by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. To detect the induction of apoptosis, Annexin V-FITC/propodium iodide (PI) staining assay was performed. Analysis of reactive oxygen species (ROS) and the distribution of cells in the cell cycle were measured by a flow cytometer. And using the Western blot analysis, the change of Fas, caspase-3, Bax, Bcl-2 activity was measured. RESULTS: The percentage of live AGS cells was decreased to 23% of that in the control group after 400 uM DADS treatment for 48 hours. The Annexin V positive/PI negative (apoptosis portion) area increased from low concentration of DADS to high concentration. When comparing among the DADS treatment groups, the amount of ROS production increased in a dose dependent manner. The percentage of sub diploid DNA content increased from 8.71% at 50 uM to 25.74% at 400 uM DADS treatment group. The expressions of Fas, caspase-3, Bax were increased and that of Bcl-2 was decreased in a dose dependent manner. CONCLUSION: DADS decreases the viability of AGS cell lines and induces apoptosis in a dose-dependent manner. But the relationship of the anti-proliferative effect of DADS and related molecular changes were not clearly proportional to the concentration of DADS. PMID- 22066107 TI - Is the critical pathway effective for the treatment of gastric cancer? AB - PURPOSE: The present study was conducted to investigate the low compliance rate of the critical pathway (CP) and whether CP is effective for treatment of gastric cancer in radical gastrectomy. METHODS: The medical records of 631 patients who had undergone radical gastrectomy with D2 lymph node dissection were reviewed. This study compared data from patients in early gastric cancer (EGC) and advanced gastric cancer (AGC) groups, which were further subdivided into general care (non CP) and CP groups. RESULTS: The mean length of preoperative hospital stays were significantly different between the EGC and AGC patients (P < 0.05). However, there was no difference in the mean length of postoperative hospital stays between non-CP and CP groups among either EGC patients or AGC patients (P > 0.05). The postoperative and total cost of hospitalization was not statistically different between either of the groups (P > 0.05); however, the mean preoperative costs were significantly different (P < 0.05). CONCLUSION: We conclude that use of the CP following gastrectomy is unnecessary. To decrease the length of hospital stay and associated costs, preoperative examination and consultation should be performed before admission. PMID- 22066108 TI - F18-fluorodeoxyglucose-positron emission tomography and computed tomography is not accurate in preoperative staging of gastric cancer. AB - PURPOSE: To investigate the clinical benefits of F18-fluorodeoxyglucose-positron emission tomography and computed tomography ((18)F-FDG-PET/CT) over multi detector row CT (MDCT) in preoperative staging of gastric cancer. METHODS: FDG PET/CT and MDCT were performed on 78 patients with gastric cancer pathologically diagnosed by endoscopy. The accuracy of radiologic staging retrospectively was compared to pathologic result after curative resection. RESULTS: Primary tumors were detected in 51 (65.4%) patients with (18)F-FDG-PET/CT, and 47 (60.3%) patients with MDCT. Regarding detection of lymph node metastasis, the sensitivity of FDG-PET/CT was 51.5% with an accuracy of 71.8%, whereas those of MDCT were 69.7% and 69.2%, respectively. The sensitivity of (18)F-FDG-PET/CT for a primary tumor with signet ring cell carcinoma was lower than that of (18)F-FDG-PET/CT for a primary tumor with non-signet ring cell carcinoma (35.3% vs. 73.8%, P < 0.01). CONCLUSION: Due to its low sensitivity, (18)F-FDG-PET/CT alone shows no definite clinical benefit for prediction of lymph node metastasis in preoperative staging of gastric cancer. PMID- 22066109 TI - Computed tomography classification for parastomal hernia. AB - PURPOSE: The aim of this study was to investigate the clinical and radiological incidence of parastomal hernia. METHODS: We reviewed, retrospectively, 83 patients with end colostomy operated on from January 2003 to June 2009 at Ajou University hospital. Age, sex, surgical procedure type, body mass index (weight/length(2)), stoma size, and respiratory co-morbidity were documented. We compared the incidence of radiological and clinical parastomal hernia. RESULTS: There were 47 males (56.6%) and 36 females (43.4%). During an overall median follow-up of 30 months (range, 6 to 45 months), 24 patients (28.9%) developed a radiological parastomal hernia postoperatively and 20 patients (24.1%) presented clinical symptoms. Using computed tomography (CT) classification, the groups were as follows: type 0 (40, 48.2%), type Ia (19, 22.9%), type Ib (8, 9.6%), type II (4, 4.8%) and type III (12, 14.5%), with 63 asymptomatic patients and 20 symptomatic patients. The aperture size was significantly different between symptomatic and asymptomatic patients (76.45 mm vs. 49.41 mm; P = 0.000). There was a significant correlation between aperture size and the radiological type (P = 0.003). CONCLUSION: This study showed the incidence of radiological parastomal hernia is acceptable compared to previous studies. CT classification may be useful to evaluate parastomal hernia. PMID- 22066110 TI - Up-regulation of cyclooxygenase-2-derived prostaglandin E(2) in colon cancer cells resistant to 5-fluorouracil. AB - PURPOSE: It has been suggested that constitutive up-regulation of cyclooxygenase (COX)-2 is associated with resistance to apoptosis, increased angiogenesis, and increased tumor invasiveness in various cancers including colon cancer. There are many factors involved in the resistance to 5-fluorouracil (5-FU) in colon cancer. However, little is known about the role of COX-2 in acquired resistance to 5-FU in colon cancer. METHODS: Hence we investigated whether COX-2 contribute to acquired resistance to 5-FU in colon cancer cells, using cytotoxicity assay for cell survival, reverse transcription-polymerase chain reaction (RT-PCR) for vascular endothelial growth factor (VEGF), quantitative RT-PCR for COX-1 and COX 2, and enzyme-linked immunosorbent assay for PGE(2). RESULTS: The 5-FU resistant colon cancer cells, SNU-C5/5FUR, showed increased expression of COX-2, prostaglandin E(2) (PGE(2)), and VEGF, compared to its parental cell (SNU-C5). By treatment with meloxicam, the expression of PGE(2) and VEGF was reduced significantly in the resistant cells, but not in the parent cells. CONCLUSION: These results demonstrate that COX-2 derived PGE(2) is up-regulated and COX-2 inhibitor may have an anti-angiogenic effect in the colon cancer cells resistant to 5-FU. PMID- 22066111 TI - Clinicopathological features of retrorectal tumors in adults: 9 years of experience in a single institution. AB - PURPOSE: Primary tumors of the retrorectal space in adults are very rare. Most of them are benign masses, but malignant masses are reported on occasion. This study aimed to investigate the clinicopathological features of retrorectal tumors. METHODS: The medical records of fifteen patients who underwent surgical resection of a retrorectal tumor from March 2002 to April 2010 in our hospital were reviewed retrospectively. RESULTS: Out of 15 patients, thirteen were females and two males. About 1.7 patients were diagnosed with retrorectal tumor annually in our hospital. The incidence is one per 1,500 surgeries performed under general anesthesia. An anterior approach was performed in eight patients and a posterior approach with excision of the coccyx in five patients. Combined approach was performed in two patients. Four patients (three in abdominal approach and one in combined approach) underwent laparoscopic resection. The mean size of tumors was 6.2 +/- 2.9 cm. Mature teratoma (four) and neurilemmoma (four) were the most common tumors. Except for one case of chondrosarcoma, fourteen tumors were confirmed to be of benign nature in histologic examination. Patients who underwent a transabdominal approach with laparoscopic surgery had no postoperative complication and had a tendency to experience earlier recovery than those with open surgery. CONCLUSION: Surgical resection of a retrorectal tumor is recommended to relieve pressure symptoms and to confirm the diagnosis. A laparoscopic approach may offer excellent visualization of the deep structures in the retrorectal space, reduce surgical trauma, and be helpful for early postoperative recovery. PMID- 22066112 TI - Laparoscopic common bile duct exploration for elderly patients: as a first treatment strategy for common bile duct stones. AB - PURPOSE: Common bile duct (CBD) stone is a relatively common disease in elderly patients. There have been many reports about the efficacy and safety of LCBDE. But for elderly patients, only a few studies about its efficacy and safety exist. The aim of this study is to evaluate the efficacy, safety and the surgical outcome of LCBDE in patients who are 70 years or older and compare the results with those of the younger group. METHODS: From January 2000 to November 2009, 132 patients underwent LCBDE. We divided these patients into two groups according to age and conducted a retrospective analysis. The elderly group included patients who were 70 years old or older (n = 64), and the younger group included those who were younger than 70 (n = 68). The elderly group was compared to the younger group with respect to their clinical characteristics, operation time, postoperative hospital stay, open conversion rate, first meal time, postoperative complication, recurrence rate and mortality. RESULTS: The elderly group showed high American Society of Anesthesiologists score (2.2 vs. 1.9) (P = 0.003), preoperative morbidity (47 vs. 29) (P < 0.001), and previous abdominal operation (18 vs. 14) (P = 0.046). There were no significant differences in mean operation time, postoperative hospital stay, first meal time, recurrence rate, remnant stone, complication rates or mortality in both groups (P > 0.05). CONCLUSION: LCDBE is a safe and effective treatment modality for CBD stones not only for younger patients but also for elderly patients. PMID- 22066113 TI - Hepatoblastoma: 15-year experience and role of surgical treatment. AB - PURPOSE: Hepatoblastoma is the most common malignant liver tumor in children. The aim of this study was to review our results of hepatoblastoma treatment and to determine the role of surgical treatment in hepatoblastoma. METHODS: This is a retrospective clinical study. The medical records of patients with hepatoblastoma, treated between October 1994 and October 2009, were reviewed. The patients were classified according to the pretreatment extent of disease (PRETEXT) grouping system. The main outcome variable was survival. Secondary outcome variables were complete, partial and no response to chemotherapy and surgery, when indicated. RESULTS: Twenty-seven patients were treated during the observation period. Eighteen were males. Five were PRETEXT group I, 8 group II, 13 group III and 1 group IV. Complete excision was achieved in all patients except in one case that underwent liver transplantation (group IV). Median follow up and survival rate were 2.3 years and 100%, 6.6 years and 75%, 5.8 years and 92%, 7.7 years and 100%, for groups I to IV, respectively. Twenty patients are currently considered to be in complete response status and three patients are receiving postoperative chemotherapy. Four patients died; the causes of death were cytomegalovirus hepatitis, bone marrow suppression during adjuvant chemotherapy, primarynonfunction after the transplantation for recurrent tumor and metachronous rectal cancer, respectively. CONCLUSION: Favorable long-term outcome could be expected for hepatoblastoma with complete tumor excision and adjuvant chemotherapy. PMID- 22066114 TI - Cystic lymphangioma of the pancreas. AB - Lymphangioma is a benign form of neoplasm arising from the lymphatic system. It occurs as a result of congenital malformations of the lymphatics leading to the obstruction of local lymph flow and the development of lymphangiectasia. Lymphangiomas are common in pediatric patients, in the soft tissues of the neck and the axillae, but lymphangioma of the pancreas is extremely rare, accounting for less than 1% of these tumors. It occurs more frequently in females and is often located in the distal pancreas. Although extremely rare, cystic lymphangioma of the pancreas should be taken into consideration as a differential diagnosis of pancreatic cystic or retroperitoneal lesions, especially in women. Herein, we report on a case of cystic lymphangioma of the distal pancreas in a 37 year-old woman who was treated with complete surgical resection with a review of the literature. PMID- 22066115 TI - Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells. AB - Undifferentiated carcinoma with osteoclast-like giant cells is a rare neoplasm of the exocrine pancreas. Some similar cases have been reported, but the histogenesis of these tumors varies and is controversial. We report here on a case of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells. A 77-year old woman presented with abdominal pain and anorexia. Abdominal computed tomography and magnetic resonance imaging showed an approximately 10 * 5 cm highly attenuated mass arising from the tail of the pancreas and invading the spleen and adjacent bowel loop. The initial impression was a malignant endocrine tumor or solid-pseudopapillary tumor of the pancreas. The patient underwent a distal pancreatectomy with splenectomy and left hemicolectomy. The histopathology and immunohistochemistry helped make the diagnosis that of an undifferentiated carcinoma with osteoclast-like giant cells of the pancreas. PMID- 22066116 TI - The current status and future perspectives of laparoscopic surgery for gastric cancer. AB - Gastric cancer is most common cancer in Korea. Surgery is still the main axis of treatment. Due to early detection of gastric cancer, the innovation of surgical instruments and technological advances, gastric cancer treatment is now shifting to a new era. One of the most astonishing changes is that minimally invasive surgery (MIS) is becoming more dominant treatment for early gastric cancer. These MIS are represented by endoscopic resection, laparoscopic surgery, robotic surgery, single-port surgery and natural orifice transluminal endoscopic surgery. Among them, laparoscopic gastrectomy is most actively performed in the field of surgery. Laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer (EGC) has already gained popularity in terms of the short-term outcomes including patient's quality of life. We only have to wait for the long-term oncologic results of Korean Laparoscopic Gastrointestinal Surgery Study Group. Upcoming top issues following oncologic safety of LADG are function-preserving surgery for EGC, application of laparoscopy to advanced gastric cancer and sentinel lymph node navigation surgery. In the aspect of technique, laparoscopic surgery at present could reproduce almost the whole open procedures. However, the other fields mentioned above need more evidences and experiences. All these new ideas and attempts provide technical advances, which will minimize surgical insults and maximize the surgical outcomes and the quality of life of patients. PMID- 22066117 TI - Clinical outcomes of TS-1 chemotherapy for advanced and recurrent gastric cancer. AB - PURPOSE: Titanium silicate (TS)-1 chemotherapy has been widely used against gastric cancer in Japan. The aim of the present study was to assess the efficacy and hematological safety of TS-1 as treatment for advanced and recurrent gastric cancer. METHODS: From September 2006 to February 2011, 51 advanced or recurrent gastric cancers were treated with TS-1. One course of treatment consisted of 40, 50, or 60 mg/m(2) of TS-1 twice a day for 28 days, followed by withdrawal for two weeks. The primary end point was progression-free survival (PFS), and the secondary end point was overall survival (OS). RESULTS: The disease control rate was 39.2% (complete response, 0/51; partial response, 6/51; stable disease, 14/51; progressive disease, 23/51; not evaluable, 8/51). The median PFS was 4.0 months (95% confidence interval [CI], 2.2 to 5.7); the median PFS of the advanced group was 6.0 months (95% CI, 2.8 to 9.1), and the median PFS of the recurrent group was 3.0 months (95% CI, 1.8 to 4.1). The median OS was 11.0 months (95% CI, 6.3 to 15.6); the median OS of the advanced group was 10.0 months (95% CI, 4.9 to 15.0), and the median OS of the recurrent group was 14.0 months (95% CI, 4.1 to 23.8). Grade 3 or 4 hematological toxicity occurred in three patients (5.9%), anemia occurred in two patients (3.9%), and thrombocytopenia occurred in one patient (2%). CONCLUSION: TS-1 chemotherapy was safe and effective, with relatively long PFS and OS in patients with advanced and recurrent gastric cancers. PMID- 22066118 TI - Long-term results in the treatment of fistula-in-ano with fibrin glue: a prospective study. AB - PURPOSE: This prospective study was done to analyze the efficacy of commercial fibrin glue application in the healing of patients with fistulas-in-ano from a long-term (mean 4.5 years) research period. METHODS: This clinical trial of forty six patients was performed during the period from January 2004 to February 2005. Thirty-nine men and seven women were treated for a fistula-in-ano with a commercial fibrin glue application. In the operating room, the patients underwent an anorectal examination under spinal anesthesia. The external and internal fistula tract openings were then identified. The fistula tract was curetted. Fibrin glue was injected into the external fistula opening until the fibrin glue could be seen coming from the internal opening. RESULTS: The overall initial success rate was 86.95% (40/46). Recurrence rate was 41.30% (19/46). Two patients underwent a re-application with fibrin glue and the fistulas of these patients closed. The total recurrence rate was 36.95% (17/46). The long-term overall success rate was 63.04% (29/46). CONCLUSION: Fibrin glue application was thus found to be an easy, safe, acceptable, successful alternative treatment in the management of fistulas-in-ano. Choosing the patient correctly is very important because long (more than 4 cm) and non-ramificate fistula tracts usually close with commercial fibrin glue. PMID- 22066119 TI - Therapeutic potential of adipose tissue-derived stem cells for liver failure according to the transplantation routes. AB - PURPOSE: Even though adipose tissue-derived stem cells (ADSCs) have been spotlighted as a possible alternative for liver transplantation in an experimental setting, the mechanism by which ADSCs improve liver dysfunction remains poorly characterized. The objective of this study was to evaluate the therapeutic ability of undifferentiated ADSCs, and find a few clues on how ADSCs alleviate liver damage by comparing the transplantation routes. METHODS: In vitro generated human ADSCs were checked for surface markers and stage-specific genes for characterization. Afterwards, they were transplanted into C57BL/6 mice with CCl4-induced liver injury. The transplantations were made via tail vein, portal vein, and direct liver parenchymal injection. At 1 and 3 post-transplantation days, serum biochemical parameters and/or liver specimens were evaluated. RESULTS: We have shown here that ADSCs have the characteristics of mesenchymal stem cells, and belong to endodermal and/or early hepatic differentiation stage. After transplantation into the mice with acute liver failure, markers of liver injury, such as alanineaminotransferase, aspartateaminotransferase, as well as ammonia, decreased. Of these transplantation routes, transplantation via tail vein rendered the most prominent reduction in the biochemical parameters. CONCLUSION: Undifferentiated ADSCs have the ability to improve hepatic function in mice with acute liver injury. Moreover, our transplantation route study supports the theory that ADSCs in systemic circulation can exert endocrine or paracrine effects to ameliorate the injured liver. PMID- 22066120 TI - Survival benefits of surgical resection in recurrent cholangiocarcinoma. AB - PURPOSE: Attempt to identify the beneficial effects associated with surgical procedures on survival outcome of patients with recurrent cholangiocarcinoma. METHODS: 921 patients diagnosed with cholangiocarcinoma underwent surgical resection with curative intent in a single institute during the last 15 years. Patients with recurrent disease were divided into two groups according to whether surgical procedures were performed for the treatment of recurrence. Clinicopathologic variables, ranges of survival based on sites of recurrence, and types of treatment were analyzed retrospectively. RESULTS: The median follow-up period was 21.8 months and 316 (34.3%) patients had recurrence. 27 (group A) patients with recurrent disease were treated surgically and 289 patients (group B) were not treated. Liver resection, metastasectomy, pancreaticoduodenectomy, partial pancreatectomy, and regional lymph node dissection were performed on the patients in group A. The overall survival rate was statistically higher in group A (P = 0.001). Among the surgical procedures, resection of locoregional recurrences (except liver) in abdominal cavity (4.0 to 101.8 months vs. 0.6 to 71.6 months) and metastasectomy of abdominal or chest wall (3.5 to 18.9 months vs. 1.9 to 2.2 months) showed remarkable differences with respect to the range of survival. CONCLUSION: Better survival outcomes can be expected by performing surgical resection of locoregional recurrences (except liver) in abdominal cavity and abdominal or chest wall metastatic lesions in recurrent cholangiocarcinoma. PMID- 22066121 TI - Management of endoscopic retrograde cholangiopancreatography-related perforations. AB - PURPOSE: The purpose of this study is to analyze the treatment strategies of patients with endoscopic retrograde cholangiopancreatography (ERCP)-related perforations. This is a retrospective study. METHODS: We experienced 13 perforations associated with ERCP. We reviewed the medical recordsand classified ERCP-related perforations according to mechanism of injury in terms of perforating device. Injury by endoscopic tip or insertion tube was classified as type I, injury by cannulation catheter or sphincterotomy knife as type II, and injury by guidewire as type III. RESULTS: Of four type I injuries, one case was managed by conservative management after primary closure with a hemoclip during ERCP. The other three patients underwent surgical treatments such as primary closure orpancreatico-duodenectomy. Of five type II injuries, two patients underwent conservative management and the other three cases were managed by surgical treatment such as duodenojejunostomy, duodenal diverticulization and pancreatico-duodenectomy. Of four type III injuries, three patients were managed conservatively and the remaining patient was managed by T-tube choledochostomy. CONCLUSION: Type I injuries require immediate surgical management after EPCP or immediate endoscopic closure during ERCP whenever possible. Type II injuries require surgical or conservative treatment according to intra- and retro peritoneal dirty fluid collection findings following radiologic evaluation. Type III injuries almost always improve after conservative treatment with endoscopic nasobilliary drainage. PMID- 22066122 TI - Inguinal hernia repair in overweight and obese patients. AB - PURPOSE: To describe the clinical characteristics and outcomes after inguinal hernia repair in overweight and obese patients. METHODS: We retrospectively reviewed the medical records of 636 adult patients who underwent mesh plug inguinal hernia repair performed by one surgeon from November 2001 to January 2009.The clinical characteristics and surgical outcomes of the patients were analyzed. According to the body mass index, patients higher than 23 were defined as overweight and obese patient group (O group) and patients between 18.5 and 23 were defined as normal weight patient group (N group). Seventeen underweight patients were excluded in this study. RESULTS: Of 619 cases, the number for O group was 344 (55.6%) and for N group was 275 (44.4%). The mean age was significantly higher in N group (62.2 +/- 12.6 vs. 64.4 +/- 14.8, P = 0.048). Underlying diseases were present in 226 (65.7%) of the O group and 191 (69.5%) of the N group (P = 0.322). Anesthesia method, operative time and postoperative hospital stay had no significant difference between the two groups. Postoperative complications developed in 41 (11.9%) of the O group and in 28 (10.2%) of the N group, respectively, and no major complications developed in either group. CONCLUSION: Adult inguinal hernias developed at a relatively younger age in overweight and obese patients than in normal weight patients. There were no specific differences in other clinical characteristics and outcomes between the two groups. Therefore inguinal hernia repair in overweight and obese patients is a safe procedure as in normal weight patients. PMID- 22066123 TI - Myoepithelial carcinoma with contralateral invasive micropapillary carcinoma of the breast. AB - Adenomyoepithelioma (AME) is a rare benign tumor composed of myoepithelial cells (MECs) which are located beneath the epithelial cells of exocrine glands, especially in breast and salivary glands. These tumor cells show biphasic proliferation of epithelial and MECs. Malignant AME is characterized by distant metastasis, local recurrence, cytologic atypia, high mitotic activity and infiltrating tumor margins. A 51-year-old woman presented with an 8 months growth in the left breast. She underwent core-needle biopsy and consecutively mammotome assisted biopsy at a local clinic. After resection, she complained about re growing remnant lesion and a newly developed solid mass in the right breast. Finally, the remnant mass in the left breast was diagnosed with myoepithelial carcinoma. Concurrently, contralateral breast mass was diagnosed with invasive micropapillary carcinoma. Herein we report an unusual case of synchronous myoepithelial carcinoma and invasive micropapillary carcinoma of the breast with a review of literatures. PMID- 22066124 TI - Intramural gallbladder hematoma mimicking gallbladder neoplasm in a 55-year-old male patient. AB - Hemorrhage in the gallbladder (GB) is usually associated with cholecystitis, GB neoplasm, trauma, hemobilia, and cystic artery aneurysm. Our patient had not experienced any previous abdominal trauma, and GB hemorrhage was unlikely to result from cholecystitis or bleeding diathesis. A 55-year-old male was admitted because of right upper quadrant pain. Both prothrombin time and partial thromboplastin time were normal. Abdominal computed tomography, endoscopic ultrasound and magnetic resonance cholangiopancreatography were performed. Image studies revealed GB wall thickening and an intraluminal mass. Laparoscopic cholecystectomy was performed. Upon opening the GB postoperatively, a large amount of fresh blood and old blood clot was noted. The incidence of GB hematoma is very rare. GB hematoma should always be considered in the differential diagnosis of GB tumor. In such a situation, surgical intervention is needed for further patient evaluation and management. We present a rare case of intramural GB hematoma, of which we were unable to make a definitive diagnosis preoperatively. PMID- 22066125 TI - Pancreatic serous cystadenocarcinoma with invasive growth into the colon and spleen. AB - Serous cystic neoplasms of the pancreas are almost always benign lesions. However, there are some case reports of malignant serous neoplasms of the pancreas. It is very difficult to distinguish malignant and benign tumors. Indeed, only clinicopathologic findings of locoregional invasion and metastasis represent a malignancy. We report a serous cystadenocarcinoma of the pancreas that was initially considered to be colon cancer. Post-operatively, the tumor was confirmed to be a malignant serous cystic tumor of the pancreas. One year later, the patient remains disease-free. PMID- 22066126 TI - Tacrolimus related neurologic complication after pediatric kidney transplantation. AB - Recently significant neurotoxicity has been reported with the use of carcineurin inhibitors. An 11-year-old-girl had undergone a transplantation of kidney from her mother. On post-operative day 12, hypertension, headache, and left motor weakness (grade I) suddenly occurred. The brain-magnetic resonance imaging and magnetic resonance angiography showed acute cerebral infarction at subcortical white matter of the right hemisphere and multiple stenoses of both anterior cerebral artery and middle cerebral artery. While stopping tacrolimus treatment, we experienced clinical and radiological improvement. So, the neurological complications of this patient seem to have been caused by the use of tacrolimus. PMID- 22066127 TI - Toward a comprehensive demography: rethinking the research agenda on change and response. AB - This essay drafts a new interdisciplinary agenda for research on population and development. Starting from Kingsley Davis's 1963 formulation of change and response, Davis's analytical categories are broadened to include inertia as well as change and to encompass both demographic and non-demographic responses at the micro, meso, and macro levels. On that basis the essay proposes what can be called a comprehensive demography, an approach drawing principally on micro-level methodologies like those employed in anthropological demography. Like anthropological demography, comprehensive demography questions the rationality of actors, emphasizes cultural infuences, and stops short of the postmodernist extremes of anthropology. But it also takes explicit account of higher-level social, economic, and political factors bearing on demographic behavior and outcomes. The conclusion raises some epistemological issues. Illustrative examples are offered throughout to demonstrate the feasibility of the approach, mainly referring to sub-Saharan africa and the Caribbean and often drawn from the authors' own fieldwork. PMID- 22066128 TI - Economic recession and fertility in the developed world. AB - This article reviews research on the effects of economic recessions on fertility in the developed world. We study how economic downturns, as measured by various indicators, especially by declining GDP levels, falling consumer confidence, and rising unemployment, were found to affect fertility. We also discuss particular mechanisms through which the recession may have influenced fertility behavior, including the effects of economic uncertainty, falling income, changes in the housing market, and rising enrollment in higher education, and also factors that influence fertility indirectly such as declining marriage rates. Most studies find that fertility tends to be pro-cyclical and often rises and declines with the ups and downs of the business cycle. Usually, these aggregate effects are relatively small (typically, a few percentage points) and of short durations; in addition they often influence especially the timing of childbearing and in most cases do not leave an imprint on cohort fertility levels. Therefore, major long term fertility shifts often continue seemingly uninterrupted during the recession including the fertility declines before and during the Great Depression of the 1930s and before and during the oil shock crises of the 1970s. Changes in the opportunity costs of childbearing and fertility behavior during economic downturn vary by sex, age, social status, and number of children; childless young adults are usually most affected. Furthermore, various policies and institutions may modify or even reverse the relationship between recessions and fertility. The first evidence pertaining to the recent recession falls in line with these findings. In most countries, the recession has brought a decline in the number of births and fertility rates, often marking a sharp halt to the previous decade of rising fertility rates. PMID- 22066129 TI - Social capital and women's reduced vulnerability to HIV infection in rural Zimbabwe. AB - Social capital-especially through its "network" dimension (high levels of participation in local community groups)-is thought to be an important determinant of health in many contexts. We investigate its effect on HIV prevention, using prospective data from a general population cohort in eastern Zimbabwe spanning a period of extensive behavior change (1998-2003). Almost half of the initially uninfected women interviewed were members of at least one community group. In an analysis of 88 communities, individuals with higher levels of community group participation had lower incidence of new HIV infections and more of them had adopted safer behaviors, although these effects were largely accounted for by differences in socio-demographic composition. Individual women in community groups had lower HIV incidence and more extensive behavior change, even after controlling for confounding factors. Community group membership was not associated with lower HIV incidence in men, possibly refecting a propensity among men to participate in groups that allow them to develop and demonstrate their masculine identities-often at the expense of their health. Support for women's community groups could be an effective HIV prevention strategy in countries with large-scale HIV epidemics. PMID- 22066130 TI - A model of greenhouse gas emissions from the management of turf on two golf courses. AB - An estimated 32,000 golf courses worldwide (approximately 25,600 km2), provide ecosystem goods and services and support an industry contributing over $124 billion globally. Golf courses can impact positively on local biodiversity however their role in the global carbon cycle is not clearly understood. To explore this relationship, the balance between plant-soil system sequestration and greenhouse gas emissions from turf management on golf courses was modelled. Input data were derived from published studies of emissions from agriculture and turfgrass management. Two UK case studies of golf course type were used, a Links course (coastal, medium intensity management, within coastal dune grasses) and a Parkland course (inland, high intensity management, within woodland).Playing surfaces of both golf courses were marginal net sources of greenhouse gas emissions due to maintenance (Links -2.2 +/- 0.4 Mg CO2e ha(-1) y(-1); Parkland - 2.0 +/- 0.4 Mg CO2e ha(-1) y(-1)). A significant proportion of emissions were from the use of nitrogen fertiliser, especially on tees and greens such that 3% of the golf course area contributed 16% of total greenhouse gas emissions. The area of trees on a golf course was important in determining whole-course emission balance. On the Parkland course, emissions from maintenance were offset by sequestration from turfgrass, and trees which comprised 48% of total area, resulting in a net balance of -5.4 +/- 0.9 Mg CO2e ha(-1) y(-1). On the Links course, the proportion of trees was much lower (2%) and sequestration from links grassland resulted in a net balance of -1.6 +/- 0.3 Mg CO2e ha(-1) y(-1). Recommendations for golf course management and design include the reduction of nitrogen fertiliser, improved operational efficiency when mowing, the inclusion of appropriate tree-planting and the scaling of component areas to maximise golf course sequestration capacity. The findings are transferrable to the management and design of urban parks and gardens, which range between fairways and greens in intensity of management. PMID- 22066131 TI - The early days of the neurosciences intensive care unit. PMID- 22066132 TI - The recombination, repair and modification of DNA. AB - This article is an overview of the author's involvement in theoretical and experimental research on genetic recombination and DNA repair, and also on the enzymic modification of cytosine in DNA to 5-methyl cytosine. It includes the history of the discovery of the central intermediate in genetic recombination at the DNA level, and the repair of mismatched bases. These explain the major features of genetic fine structure. The first repair and recombination defective mutants in any eukaryote were isolated in the smut fungus Ustilago maydis. The hypothesis that DNA methylation has a role in gene expression in higher organism is now supported by abundant evidence. Direct evidence that gene silencing in mammalian cells is causally related to DNA methylation has been obtained. PMID- 22066133 TI - Notice of duplicate publication. AB - The Journal of the American Dental Association has learned that the results of a study described in a February 2010 JADA article were published previously. An article by Dr. Masoumeh Moslemi and colleagues entitled "The Effect of Er, Cr:YSGG Laser and Air Abrasion on Shear Bond Strength of a Fissure Sealant to Enamel" contained results of research previously published in The Journal of Islamic Dental Association of Iran (JIDA). PMID- 22066134 TI - Symmetrical ventricular lesions in an adolescent male. PMID- 22066135 TI - Posterior fossa mass with multiple cranial neuropathies. PMID- 22066136 TI - Frontal intra-axial mass lesion in an adult. Invasive aspergillosis. PMID- 22066137 TI - A cystic lesion in the fourth ventricle. Dermoid cyst. PMID- 22066138 TI - Sound and fury after stem cell ruling. PMID- 22066139 TI - Mending mental health in Misrata. PMID- 22066140 TI - A search for wisdom. PMID- 22066141 TI - Max Harry (Hal) Weil, MD, PhD, ScD (hon), MACP Master, FCCP, FACC, FCCM, FAHA 1927 to 2011. PMID- 22066142 TI - Retinoid X receptor alpha acts as a negative regulator in Nurr1-induced dopaminergic differentiation in rat neural precursor cells. PMID- 22066143 TI - Retinoid X receptor alpha acts as a negative regulator in Nurr1-induced dopaminergic differentiation in rat neural precursor cells. AB - To investigate the role of retinoid X receptor (RXRalpha)-Nurr1 heterodimers in tyrosine hydroxylase (TH) expression, we observed retrovirus-induced RXRalpha Nurr1 heterodimer interactions with, and transactivation of, the TH promoter region in cultured rat embryonic neural precursor cells. Interestingly, forced expression of RXRalpha with Nurr1 remarkably reduced Nurr1 activity in TH+ dopaminergic neuron generation and significantly down-regulated TH promoter activity. These regulatory activities were altered in both Nurr1dim- and RXRalphadim- that disrupted dimeric binding, verifying that the Nurr1-RXRalpha heterodimer represses TH promoter activity. Therefore, a plausible explanation for the inhibitory role of RXRalpha in Nurr1-induced TH expression is that RXRalpha differentially affects an inhibitory element of the TH promoter. PMID- 22066144 TI - The ESC goes global: policies to prevent all chronic diseases. PMID- 22066145 TI - A pioneer in cardiology, professor Sir Salvador Moncada MD, PhD, FRS. PMID- 22066146 TI - Systematic review and meta-analysis of pre-clinical research: the need for reporting guidelines. PMID- 22066149 TI - Donor conception and sharing of genetic information. PMID- 22066150 TI - Between state power and popular desire: tobacco in pre-conquest Manchuria, 1600 1644. AB - Tobacco entered Manchuria on the same wave of early modern globalization that brought it from the Americas to other parts of Eurasia in the early seventeenth century. Introduced into northeast Asia sometime after 1600, it began to circulate widely in Manchuria precisely at a time when Hong Taiji (1592-1643) was building the early Qing state. This essay examines Hong Taiji's efforts to criminalize tobacco in the 1630s and 1640s, arguing that these prohibitions were largely directed at gaining state control over a valuable economic resource. However, within the commercialized milieu of seventeenth-century Liaodong, a region with ties to broader transregional circuits of trade, tobacco's lucrative profits and its pleasurable allure simply overpowered state efforts to monopolize it. As in most other early seventeenth-century Eurasian societies, the Qing tobacco bans quickly gave way to legalization and taxation. PMID- 22066151 TI - Between passion and repression: medical views of demon dreams, demonic fetuses, and female sexual madness in late imperial China. AB - This article argues that early Chinese physicians had already related female ailments to their sexual frustration. Moreover, many physicians paid more attention to non-reproductive women - nuns, widows, and unmarried women - as if they were more prone to suffer from unfulfilled desires and sexual frustration and, as a result, produce the sexual dreams and monstrous births that were described in the medical literature of medieval China as physical ailments. The earlier body-oriented etiology of these female illnesses gradually shifted to emotion-oriented perspectives in late imperial China. In particular, the sixteenth- and seventeenth-century doctors began to categorize women's sexual frustration as "yu disorders" or "love madness." In this article I will show not only the changing medical views of female sexual madness throughout the ages, but how these views were shaped by the societies in which both the doctors and patients were situated. PMID- 22066152 TI - The pharmacological tables of Rhazes. AB - This article deals with the 22nd volume of Muhammad ibn Zakariya' al-Razi's (Rhazes, d. 313/925) medical encyclopedia al-Hawi fi l-tibb. Volume twenty-two is dedicated to pharmacology and pharmacological tables, and introduced by a short treatise in which Rhazes explains his unusual choice of tabular design and terminological arrangement. Following upon a brief bio-bibliographical survey and forming the core of this article, Rhazes' introductory treatise is re-edited here in the original Arabic and further made accessible through an annotated English translation. Edition and translation, in turn, are followed by a detailed study of both the treatise and the tables, including explanatory diagrams, statistical evaluations, a source-critical analysis, and some observations regarding the tradition of synoptic tables in Arabic pharmaceutical literature - thus gradually emerges the conceptual originality of Rhazes' implementation, and new light is thrown on his broad linguistic interests and abilities. The article concludes with an excursion into the realm of Persian-Chinese intellectual exchange, suggesting the possibility of a stimulus to Rhazes' imagination from a remote and otherwise mostly hidden corner. PMID- 22066153 TI - Community, difference and identity: the case of the Irish in Sheffield. AB - There is a growing body of research in racial and ethnic studies on the processes of identity construction within minority ethnic populations. This article seeks to build on this work by analysing emerging collective identity formations in an 'invisible' minority ethnic group. Based upon focus groups and in-depth interviews with Irish people in Sheffield, the article aims to advance three key arguments. First, the concept of community is central to an Irish collective identity, but is negotiated in a multiplicity of ways. Second, Irish collective identity has been shaped not only by demographic differences but by shared experiences of non-recognition and stereotyping. Third, there is a simultaneous assertion of an Irish identity running parallel with a perception that the 'traditional' Irish community may have to re-invent itself in response to changing demographics at the local level. The paper concludes by considering the implications of these arguments for an understanding of Irish ethnicity in multicultural Britain. PMID- 22066154 TI - A pragmatic assessment of government support for organic agriculture in Ireland. AB - Drawing on a pragmatic approach, this paper provides an analysis of government support for organic farming in Ireland. Varying levels of encouragement and programmes are provided to farmers in their conversion from conventional to organic production, and in their maintenance of organic production. As support policies vary across regions and are linked to European Union legislation, it is challenging to document the many types of support in place. This paper investigates relevant technical, financial, and policy support available to organic farmers in Ireland. As an exploratory study, it develops an assessment of Ireland within eight key categories of organic agricultural support: policy, leadership, technical support, financial support, research, education and information, marketing and promotion, and future outlook. Information and data from the Irish Department of Agriculture, Fisheries and Food (DAFF), the Irish Agriculture and Food Development Authority (Teagasc), and other government and semi-governmental agencies were utilized to assess the level of support in each category. This assessment provides key findings which will allow policymakers, organizations and citizens to better understand the current situation and set a path for the future development of organic farming in Ireland. PMID- 22066155 TI - The goal of the Journal of Invasive Cardiology is to provide state-of-the-art information that will support clinicians in the effective management of patients with cardiovascular disease. Introduction. PMID- 22066156 TI - [Genital cancers in the woman]. PMID- 22066158 TI - [The financial administration of a village hospital: Allauch in the 18th century]. PMID- 22066159 TI - [The brides and grooms of 1810 in Vaucluse: imperial manna and social reality]. PMID- 22066160 TI - [Post doc in the USA - a report of experiences]. PMID- 22066161 TI - [Compulsory care with a question mark]. PMID- 22066162 TI - [To breastfeed or not to breastfeed and unnuanced opinion. "Knattetanger" and breast feeding fascism]. PMID- 22066163 TI - [EQUALIS expert group for coagulation. Functional method for the first choice diagnostics of hereditary antithrombin deficiency]. PMID- 22066164 TI - [40 percent of high school pupils abuse alcohol. Strong connection with exposure to physical or sexual violence]. PMID- 22066165 TI - [Specialized pain teams and primary health care in sparsely populated areas--a painless cooperation. Team-based work for patients with chronic pain assessed]. PMID- 22066166 TI - [Hereditary antithrombin deficiency--rare, but serious. Great risk of venous thromboembolism]. PMID- 22066167 TI - [DSM-5: Psychiatry widens its territory]. PMID- 22066168 TI - [Ambiguous and difficult to interpret results on the effect of antipsychotics on brain volume]. PMID- 22066169 TI - [Counterproductive not to treat streptococcal throat infection]. PMID- 22066170 TI - [The National Board of Health and Welfare on breast feeding recommendation: matter-of-fact and objective information can never be unethical]. PMID- 22066171 TI - [A definite biological marker]. PMID- 22066172 TI - Oxygen enhances phosphine toxicity for postharvest pest control. AB - Phosphine fumigations under superatmospheric oxygen levels (oxygenated phosphine fumigations) were significantly more effective than the fumigations under the normal 20.9% atmospheric oxygen level against western flower thrips [Frankliniella occidentalis (Pergande)] adults and larvae, leafminer Liriomyza langei Frick pupae, grape mealybug [Pseudococcus maritimus (Ehrhorn)] eggs, and Indianmeal moth [Plodia interpunctella (Hubner)] eggs and pupae. In 5-h fumigations with 1,000 ppm phosphine at 5 degrees C, mortalities of western flower thrips increased significantly from 79.5 to 97.7% when oxygen was increased from 20.9 to 40% and reached 99.3% under 80% O2. Survivorships of leafminer pupae decreased significantly from 71.2% under 20.9% O2 to 16.2% under 40% O2 and reached 1.1% under 80% O2 in 24-h fumigations with 500 ppm phosphine at 5 degrees C. Complete control of leafminer pupae was achieved in 24-h fumigations with 1,000 ppm phosphine at 5 degrees C under 60% O2 or higher. Survivorships of grape mealybug eggs also decreased significantly in 48-h fumigations with 1,000 ppm phosphine at 2 degrees C under 60% O2 compared with the fumigations under 20.9% O2. Indian meal moth egg survivorships decreased significantly from 17.4 to 0.5% in responses to an oxygen level increase from 20.9 to 40% in 48-h fumigations with 1,000 ppm phosphine at 10 degrees C and reached 0.2% in fumigations under 80% O2. When the oxygen level was reduced from 20.9 to 15 and 10% in fumigations, survivorships of Indianmeal moth eggs increased significantly from 17.4 to 32.9 and 39.9%, respectively. Increased O2 levels also resulted in significantly lower survival rates of Indianmeal moth pupae in response to 24-h fumigations with 500 and 1,000 ppm phosphine at 10 degrees C and a complete control was achieved in the 1,000 ppm phosphine fumigations under 60% O2. Oxygenated phosphine fumigations have marked potential to improve insecticidal efficacy. Advantages and limitations of oxygenated phosphine fumigation are discussed. PMID- 22066173 TI - Modeling the sterile insect technique for suppression of light brown apple moth (Lepidoptera: Tortricidae). AB - A population model was derived for light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae), subject to the sterile insect technique (SIT). The model was parameterized from the literature and from recent laboratory studies conducted in New Zealand and Australia. Relationships were fitted for several model parameters that vary with irradiation dose, allowing the model to simulate effectively complete sterility at 300 Gy through inherited sterility occurring from lower doses. At 300 Gy, the model suggests that eventual population extinction is 95% probable when the ratio of released to wild males in monitoring traps exceeds 6.4. Higher overflooding rates would be required to achieve eradication more rapidly. The optimal release interval, in terms of minimizing the required rate of production of factory moths, is approximately weekly. There is little advantage in releasing males only compared with releasing both sexes. Female-only releases are unlikely to be a useful tool for inherited sterility eradication because there is no reduction in the fertility of F1 offspring. The critical release rate required to halt population increase declines with decreasing irradiation dose, but at doses of < 171 Gy there is a risk that irradiated-lineage moths may form a self-sustaining population, making eradication by SIT alone impossible. The model suggests that a dose of around 200 Gy may be optimal because the resulting inherited sterility would reduce by a third the number of factory moths required compared with 300 Gy. PMID- 22066174 TI - Cross-pollination of nontransgenic corn ears with transgenic Bt corn: efficacy against lepidopteran pests and implications for resistance management. AB - The efficacy of nontransgenic sweet corn, Zea mays L., hybrids cross-pollinated by Bacillus thuringiensis (Bt) sweet corn hybrids expressing Cry1Ab toxin was evaluated in both field and laboratory studies in Minnesota in 2000. Non-Bt and Bt hybrids (maternal plants) were cross-pollinated with pollen from both non-Bt and Bt hybrids (paternal plants) to create four crosses. Subsequent crosses were evaluated for efficacy in the field against European corn borer, Ostrinia nubilalis (Hubner), and corn earworm, Helicoverpa zea (Boddie), and in laboratory bioassays against O. nubilalis. Field studies indicated that crosses with maternal Bt plants led to low levels of survival for both O. nubilalis and H. zea compared with the non-Bt x non-Bt cross. However, the cross between non-Bt ears and Bt pollen led to survival rates of 43 and 63% for O. nubilalis and H. zea larvae, respectively. This intermediate level of survival also was reflected in the number of kernels damaged. Laboratory bioassays for O. nubilalis, further confirmed field results with larval survival on kernels from the cross between non-Bt ears and Bt pollen reaching 60% compared with non-Bt crossed with non-Bt. These results suggest that non-Bt refuge plants, when planted in proximity to Bt plants, and cross-pollinated, can result in sublethal exposure of O. nubilalis and H. zea larvae to Bt and may undermine the high-dose/refuge resistance management strategy for corn hybrids expressing Cry1Ab. PMID- 22066175 TI - Effect of host plant tissue on the vector transmission of grapevine leafroll associated virus 3. AB - Many biotic and abiotic factors affect the transmission efficiency of vector borne plant pathogens. Insect vector within-plant distribution and host tissue preference are known to affect pathogen acquisition and inoculation rates. In this study, we first investigated whether feeding tissue affects the transmission of Grapevine leafroll-associated virus 3 by Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae) and the effect of mealybug within-plant distribution on virus transmission under greenhouse conditions. Results showed no significant effect on transmission efficiency after insect confinement on leaf blades, petioles or stems of virus source or healthy test plants for either acquisition or inoculation trials. Transmission efficiency of a single mealybug varied from 4 to 25% in those trials. Second, we tested whether leaf position affected transmission efficiency due to potentially variable virus populations within acquisition plant tissues. No significant differences of transmission rate among acquisition leaf position were observed, probably because there were no differences in the virus population within source tissues. Finally, we examined the seasonality of the virus in field-collected samples and found that GLRaV-3 prevalence varied along a growing season, such that GLRaV-3 translocated along expanding shoots to leaves. Similarly, mealybug populations are known to increase in spring, and then mealybugs spread to cordons and leaves. This coordination of spatial and temporal dynamics of the virus and its vector may increase the risk of GLRaV-3 transmission during late spring and early summer. Further integration of information about pathogen populations in plants, vector feeding behavior and vector population seasonality could lead to more effective management practices. PMID- 22066176 TI - Vector transmission efficiency of liberibacter by Bactericera cockerelli (Hemiptera: Triozidae) in zebra chip potato disease: effects of psyllid life stage and inoculation access period. AB - Successful transmission of plant pathogens by insects depends on the vector inoculation efficiency and how rapidly the insect can effectively transmit the pathogen to the host plant. The potato psyllid, Bactericera cockerelli (Sulc), has recently been found to transmit "Candidatus Liberibacter solanacearum," a bacterium associated with zebra chip (ZC), an emerging and economically important disease of potato in several parts of the world. Currently, little is known about the epidemiology of ZC and its vector's inoculation capabilities. Studies were conducted in the field and laboratory to 1) assess transmission efficiency of potato psyllid nymphs and adults; 2) determine whether psyllid inoculation access period affects ZC incidence, severity, and potato yield; and 3) determine how fast the psyllid can transmit liberibacter to potato, leading to ZC development. Results showed that adult potato psyllids were highly efficient vectors of liberibacter that causes ZC and that nymphs were less efficient than adults at transmitting this bacterium. It was also determined that inoculation access period had little influence on overall ZC disease incidence, severity, and resulting yield loss. Moreover, results showed that exposure of a plant to 20 adult potato psyllids for a period as short as 1 h resulted in ZC symptom development. Furthermore, it was shown that a single adult potato psyllid was capable of inoculating liberibacter to potato within a period as short as 6 h, thereby inducing development of ZC. This information will help in developing effective management strategies for this serious potato disease. PMID- 22066177 TI - Does use of pesticides known to harm natural enemies of spider mites (Acari: Tetranychidae) result in increased number of miticide applications? An examination of California walnut orchards. AB - Integrated pest management (IPM) offers guidelines to reduce spider mite (Acari: Tetranychidae) outbreaks by avoiding pesticides known to be harmful to the natural enemies of spider mites. However, in practice, these guidelines can be inconsistent in their effectiveness. The project examined whether California walnut (Juglans L.) growers, following IPM guidelines to avoid pesticides harmful to the natural enemies of spider mites, achieved lower miticide use. Significant statistical tests suggested that fields with harmful applications were 40% more likely to have a miticide application than fields without. Although the IPM guidelines achieved the goal of reducing miticide use, further analysis of other potential causal mechanisms behind outbreaks could strengthen the effectiveness of the guidelines, potentially increasing IPM adoption. PMID- 22066178 TI - Bacillus subtilis subspecies virginiana, a new subspecies of antitermitic compound-producing endophytic bacteria isolated from Juniperus virginiana. AB - Termites are worldwide pests causing considerable damage to agriculture, forestry and buildings. Although physical and chemical methods have been tried to eliminate termite populations, they have the limitations such as low effectiveness, high-toxicity residue, environmentally harmful and high cost. Therefore, it has attracted much attention to develop highly effective, low toxic, long residual period, environmentally friendly and low-cost termiticidals. Here, we report the characterization and antitermitic activities of a new antitermitic compound-producing endophytic bacterium HUB-I-47 isolated from eastern red-cedar, Juniperus virginiana L. The morphological, physiochemical characteristics of strain HUB-I-47 and its 16S rDNA sequences, and the antitermitic compound were analyzed by gas chromatography-mass spectrometry were studied. We found that the morphology of HUB-I-47 was very similar to that of Bacillus subtilis but presented some differences in shape and cell size. Growth evaluation showed that the lowest, highest, and optimum growth temperatures of HUB-I-47 were 12, 47, and 31 degrees C, respectively, which were different from those of reference strains. The 16S rDNA sequence analysis revealed a high similarity of 99% to those of B. subtilis. Based on these analyses, we named strain HUB-I-47 as B. subtilis subsp. virginiana D. P. Zhou, K. Zhao, J. Liu et W. X. Ping, subsp. nov. This is the first report on the analysis of antitermitic compounds from endophytic bacteria. Our study identified a new resource of antitermitic compounds through endophytic bacteria fermentation. PMID- 22066179 TI - Generic phytosanitary radiation treatment for tephritid fruit flies provides quarantine security for Bactrocera latifrons (Diptera: Tephritidae). AB - Bactrocera latifrons (Hendel) (Diptera: Tephritidae) is a quarantine pest of several solanaceous crops and tropical fruits that are treated using irradiation before export from Hawaii to the U.S. mainland. A dose of 150 Gy is approved as a generic irradiation treatment for tephritid fruit flies, but no confirmation of efficacy has been reported for B. latifrons. Dose response of B. latifrons was used to determine the most tolerant life stage and identify a dose that prevents adult emergence. Data indicated doses (plus 95% confidence limits) required to prevent adult emergence of 13.4 (10.0-29.6), 17.5 (14.4-24.8), and 88.1 (68.0 133.8) Gy for eggs, first instars and third instars, respectively. In large-scale confirmatory tests of the most radiotolerant life stage, a radiation dose of 150 Gy applied to B. latifrons late third instars in bell peppers (Capsicum annuum L.) resulted in no survival to the adult stage of 157,112 individuals, a treatment efficacy consistent with Probit 9-level mortality. The relative radiotolerance of melon fly Bactrocera cucurbitae Coquillet, and B. latifrons also was tested using a diagnostic radiation dose of 30 Gy. In diet, a mean of 6.9% of irradiated B. cucurbitae third instars developed to the adult stage, whereas no B. latifrons third instars developed to adults. In papaya, Carica papaya L., fruit, a mean of 3.3% of irradiated B. cucurbitae third instars developed to the adult stage, whereas 0.5% B. latifrons third instars developed to adults. This report supports the use of a generic radiation dose of 150 Gy in quarantine scenarios to control tephritid fruit flies on fresh commodities. PMID- 22066180 TI - Worldwide host plants of the highly polyphagous, invasive Epiphyas postvittana (Lepidoptera: Tortricidae). AB - The light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae), is a highly successful biological invader. It was accidentally introduced to several countries including New Zealand, Hawaii, England, and California. Light brown apple moth attacks a wide range of crop plants and other woody and herbaceous plants, but a more comprehensive analysis of its host range is needed for risk assessments, to evaluate the likely economic and environmental impacts, and to enable targeting of particular plant species for detection surveys and treatments. We reviewed and synthesized the host range and host selection behavior of light brown apple moth by using information from Australia and invaded countries. The host range of light brown apple moth is determined by the behavior of both adult females and larvae. Females use visual, chemical and physical cues to choose host plants. Larvae are capable of limited active dispersal by walking and longer range dispersal by ballooning on silken strands; therefore, larvae also may need to select host plants. We review larval performance indicators across a range of plants. Based on our review, there are at least 545 plant species in 363 genera from 121 families that have been reported as hosts of light brown apple moth. Some plants were reported only once and need verification. Nevertheless, many host plant species and their wide phylogenetic range (from ferns to higher dicotyledons) indicates that light brown apple moth is one of the most polyphagous insects known. This information and our categorization of frequency of host use are valuable for incursion response and pest management activities. PMID- 22066181 TI - Temperature-dependent demography of Chilades pandava peripatria (Lepidoptera: Lycaenidae). AB - Chilades pandava peripatria Hsu and its host plant Cycas taitungensis Shen, Hill, Tsou & Chen are both endemic species to Taiwan. Ch. pandava peripatria has a specific association with buds and soft leaves of cycad plants. The introduced species, Cy. revoluta, have prolonged budding periods and extensive auxiliary buds that extensively contribute to the outbreak of Ch. pandava peripatria. An in depth knowledge of the development, survival, and fecundity of Ch. pandava peripatria under different environmental conditions is necessary to understand the population growth of Ch. pandava peripatria. The demography of Ch. pandava peripatria was studied based on the age-stage, two-sex life table at 20, 23, 25, 28, and 31 degrees C, 70% RH, and a photoperiod of 16:8 (L:D) h under laboratory conditions. Ch. pandava peripatria completed its development under tested temperatures but did not produce offsprings at 23 degrees C. Because of the high egg mortality at 20 degrees C, the data at this given temperature were excluded from this study. The intrinsic rate of increase (r) under these tested temperatures was 0.1846, 0.2919, and 0.1412 d(-1), respectively. The net reproductive rate (H(o)) was 165.47, 262.32, and 56.68 offsprings per individual and the mean generation time (T) was 27.72, 19.10, and 28.67 d, respectively. Our results indicated that Ch. pandava peripatria is highly adaptable to environments where temperature ranges from 25 to 31 degrees C. PMID- 22066182 TI - Bioefficacy of Alpinia galanga (Zingiberaceae) rhizome extracts, (E)-p acetoxycinnamyl alcohol, and (E)-p-coumaryl alcohol ethyl ether against Bactrocera dorsalis (Diptera: Tephritidae) and the impact on detoxification enzyme activities. AB - The application of insecticides to control oriental fruit fly, Bactrocera dorsalis Hendel (Diptera: Tephritidae), is a principal component of the current management of these fruit flies. However, we evaluated four extracts of Alpinia galanga Wild Linn (Zingiberaceae) rhizomes against adult flies and found hexane and ethanol extracts to be most effective (LC50 = 4,866 and 6,337 ppm, respectively, after 24 h). This suggested that both nonpolar and polar compounds could be active in the candidate plant. Accordingly, the hexane extract was further processed to isolate nonpolar active compounds from this plant source. Two compounds, (E)-p-acetoxycinnamyl alcohol and (E)-p-coumaryl alcohol ethyl ether, were identified as active ingredients and found to be more active than total hexane extract (LC50 = 3,654 and 4,044 ppm, respectively, after 24 h). The data suggested that the compounds were not synergistic but may have some additive effect in a mixture. The activity of the hexane extract against detoxification enzymes, carboxylesterase (CE) and glutathione transferase (GST) also was determined in vitro. CE was inhibited by 70%, whereas GST was not significantly inhibited. Insect CEs mediate insecticide resistance via their induction; therefore, inhibition of these enzymes by plant allelochemicals could be a useful alternative approach for the management of the pest in the field. PMID- 22066183 TI - Lethal and sublethal toxicity of fipronil and imidacloprid on Psyttalia concolor (Hymenoptera: Braconidae). AB - Psyttalia concolor (Szepligeti) (Hymenoptera: Braconidae) is a koinobiont endoparasitoid of several species of tephritid (Diptera) larvae, such as Bactrocera oleae (Gmelin) and Ceratitis capitata (Wiedemann). Here, we report on the effects of imidacloprid and fipronil on P. concolor females, when different routes of exposure were evaluated: residual contact (cover and bait sprays) and via treatment of host species. Moreover, the persistence of the bait formulated compound also was studied. For each experiment, lethal (mortality) and sublethal effects (parasitization rate or longevity) were studied. Fipronil produced 100% mortality irrespective of exposure route, and it was very persistent, because 34 d-old residues still produced this high mortality rate, being as toxic or even more toxic than the reference product dimethoate. Toxicity of imidacloprid depends on the mode of exposure, although always remained less toxic than dimethoate. Imidacloprid caused high mortality or sublethal effect to the progeny in cover sprays and when applied via treated host, being harmless in bait sprays application. In conclusion, our results suggest that fipronil should not be used in the field when the parasitoid is present. On the contrary, although imidacloprid is physiologically active against females of P. concolor, ecological selectivity may result through the use of bait treatment. PMID- 22066184 TI - Response of Pisum sativum (Fabales: Fabaceae) to Sitona lineatus (Coleoptera: Curculionidae) infestation: effect of adult weevil density on damage, larval population, and yield loss. AB - Sitona lineatus L. (Coleoptera: Curculionidae) is an invasive pest in North America and its geographical range is currently expanding across the Canadian prairies. Adults and larvae of S. lineatus feed upon the foliage and root nodules, respectively, of field pea, Pisum sativum L. (Fabales: Fabaceae), and may contribute to economic losses when population densities are high. Integrated pest management (IPM) programs that incorporate economic thresholds should be used to manage S. lineatus populations in a sustainable manner. The impact of nitrogen fertilizer on field pea yield and the relationships between adult weevil density and above- and below-ground damage and yield were investigated in southern Alberta, Canada using exclusion cages on field pea plots. In each cage, 32 field pea plants were exposed to weevil densities ranging from zero to one adult weevil per plant. Nitrogen-fertilized plants yielded 16% more than unfertilized plants. Nitrogen-fertilized plants had fewer root nodules than unfertilized plants, but fertilizer had no effect on foliar feeding by S. lineatus. Adult density affected foliar feeding damage, with increases in above ground damage associated with increases in S. lineatus density. Adult density did not affect root nodule damage, larval density, foliar biomass or seed weight. Overall, these results indicate that terminal leaf damage may be used to estimate adult weevil density but cannot be used to predict larval density or yield loss. Further research is required to better understand the impact of larval damage on yield and determine if economic thresholds can be developed using data from large scale production systems. PMID- 22066185 TI - Relative feeding and development of armyworm on switchgrass and corn, and its potential effects on switchgrass grown for biomass. AB - To help assess the potential for damage by armyworms [Mythimna (Pseudaletia) unipuncta (Haworth) (Lepidoptera: Noctuidae)] to switchgrass (Panicum virgatum L.) and surrounding crops, survival and development were evaluated for larvae reared on leaves of switchgrass, corn (Zea mays L.), and miscanthus (Miscanthus x giganteus Greef and Deuter ex Hodkinson and Renvoize). Additional tests assessed the relationship between leaf position and the concentration of saponins (plant compounds which can provide protection from insect herbivores) and examined the effect of defoliation on switchgrass dry mass. Survival to adulthood was similar when larvae were reared on field-grown leaves of switchgrass and corn. However, lower larval mass (10 d) and delayed development of M. unipuncta (to pupation, adult emergence) suggest switchgrass is an inferior host relative to corn. When fed field-grown miscanthus, no larvae survived 10 d. Few differences were noted between switchgrass and corn grown under controlled (laboratory) conditions, but M. unipuncta survival seemed to decline rapidly when larvae were fed the fourth and fifth leaves of switchgrass. Switchgrass leaf samples collected from different leaf positions and stages of tiller maturity showed up to 10-fold differences in the concentration of the saponin protodioscin, with the greatest concentrations in the fourth and fifth leaves. However, other saponins showed an opposite pattern, indicating the role of protodioscin on insect development should be tested in isolation (e.g., by addition of the purified compound to an artificial diet). Defoliation trials indicated that extremely high M. unipuncta populations may be necessary to cause any significant reduction in switchgrass biomass. Collectively, results suggest M. unipuncta may not present a significant risk to biomass production in switchgrass, but that the spring emergence of switchgrass provides an alternate host for M. unipuncta before colonizing annual food and feed crops. PMID- 22066186 TI - Soybean aphid and soybean cyst nematode interactions in the field and effects on soybean yield. AB - How above- and belowground plant pests interact with each other and how these interactions affect productivity is a relatively understudied aspect of crop production. Soybean cyst nematode, Heterodera glycines Ichinohe, a root parasite of soybean, Glycine max (L.) Merr., is the most threatening pathogen in soybean production and soybean aphid, Aphis glycines Matsumura, an aboveground phloem feeding insect that appeared in North America in 2000, is the key aboveground herbivore of soybean in the midwestern United States. Now, both soybean aphid and soybean cyst nematode co-occur in soybean-growing areas in the Upper Midwest. The objectives of this study were to examine aphid colonization patterns and population growth on soybean across a natural gradient of nematode density (range, approximately 900 and 27,000 eggs per 100 cm3 soil), and to investigate the effect of this pest complex on soybean productivity. Alate (winged) soybean aphid colonization of soybean was negatively correlated to soybean cyst nematode egg density (r = -0.363, P = 0.0095) at the end of July, at the onset of peak alate colonization. However, both a manipulative cage study and openly colonized plants showed that soybean cyst nematode density below ground was unrelated to variation in aphid population growth (r approximately -0.01). Based on regression analyses, soybean aphids and cyst nematodes had independent effects on soybean yield through effects on different yield components. High soybean cyst nematode density was associated with a decline in soybean yield (kg ha(-1)), whereas increasing soybean aphid density (both alate and apterous) significantly decreased seed weight (g 100 seeds(-1)). PMID- 22066187 TI - Impact of Lygus spp. (Hemiptera: Miridae) on damage, yield and quality of lesquerella (Physaria fendleri), a potential new oil-seed crop. AB - Lesquerella, Physaria fendleri (A. Gray) S. Watson, is a mustard native to the western United States and is currently being developed as a commercial source of valuable hydroxy fatty acids that can be used in a number of industrial applications, including biolubricants, biofuel additives, motor oils, resins, waxes, nylons, plastics, corrosion inhibitors, cosmetics, and coatings. The plant is cultivated as a winter-spring annual and in the desert southwest it harbors large populations of arthropods, several of which could be significant pests once production expands. Lygus spp. (Hemiptera: Miridae) are common in lesquerella and are known pests of a number of agronomic and horticultural crops where they feed primarily on reproductive tissues. A 4-yr replicated plot study was undertaken to evaluate the probable impact of Lygus spp. on production of this potential new crop. Plant damage and subsequent seed yield and quality were examined relative to variable and representative densities of Lygus spp. (0.3-4.9 insects per sweep net) resulting from variable frequency and timing of insecticide applications. Increasing damage to various fruiting structures (flowers [0.9-13.9%], buds [1.2 7.1%], and seed pods [19.4-42.5%]) was significantly associated with increasing pest abundance, particularly the abundance of nymphs, in all years. This damage, however, did not consistently translate into reductions in seed yield (481-1,336 kg/ha), individual seed weight (0.5-0.7 g per 1,000 seed), or seed oil content (21.8-30.4%), and pest abundance generally explained relatively little of the variation in crop yield and quality. Negative effects on yield were not sensitive to the timing of pest damage (early versus late season) but were more pronounced during years when potential yields were lower due to weed competition and other agronomic factors. Results suggest that if the crop is established and managed in a more optimal fashion, Lygus spp. may not significantly limit yield. Nonetheless, additional work will be needed once more uniform cultivars become available and yield effects can be more precisely measured. Densities of Lygus spp. in unsprayed lesquerella are on par with those in other known agroecosystem level sources of this pest (e.g., forage and seed alfalfa, Medicago sativa L.). Thus, lesquerella production may introduce new challenges to pest management in crops such as cotton. PMID- 22066188 TI - Mortality impact of Bt transgenic maize roots expressing eCry3.1Ab, mCry3A, and eCry3.1Ab plus mCry3A on western corn rootworm larvae in the field. AB - Mortality of the western corn rootworm, Diabrotica virgifera virgifera LeConte, larvae due to feeding on maize, Zea mays L., expressing Bacillus thuringiensis Berliner (Bt) was evaluated in five Missouri sites in 2007, 2008, and 2009. Specifically, eCry3.1Ab (5307), mCry3A (MIR604), and eCry3.1Ab plus mCry3A proteins relative to survivorship on maize with the same genetic background without these genes (isoline maize) was evaluated. An average of 890.8 +/- 152.3 beetles emerged from isoline plots, whereas average beetle emergence from 5307, MIR604, and 5307 x MIR604 was 1.9 +/- 0.6, 19.3 +/- 6.3, and 0.8 +/- 0.3, respectively, when averaged across 22 replications in five environments. Overall, 66, 50, 61, and 51% of beetles recovered from 5307, MIR604, 5307 x MIR604, and isoline maize, respectively, were female, and there was no significant difference between the number of male and female beetles that emerged from any of these treatments. Mortality due to 5307, MIR604, and 5307 x MIR604 was 99.79, 97.83, and 99.91%, respectively. There was an 8.0-d delay in time to 50% beetle emergence from 5307 compared with isoline maize, which was significantly later than to the other three maize lines. The average delay to 50% emergence from MIR604 and 5307 x MIR604 averaged 4.1 and 4.6 d, respectively later than 50% emergence from isoline maize. Female beetles had a significant delay in time to 50% emergence compared with male beetles from all treatments with the exception of 5307 x MIR604. Data are discussed in terms of insect resistance management in relation to other control measures for western corn rootworm. PMID- 22066189 TI - A male-produced aggregation pheromone of Monochamus alternatus (Coleoptera: Cerambycidae), a major vector of pine wood nematode. AB - The beetle Monochamus alternatus Hope (Coleoptera: Cerambycidae) is an efficient vector of pine wood nematode, the causal pathogen of pine wilt disease, that has resulted in devastating losses of pines in much of Asia. We assessed the response of adult M. alternatus to 2-(undecyloxy)-ethanol, the male-produced pheromone of the congeneric M. galloprovincialis Dejean, in field experiments in Fujian Province, People's Republic of China. Both sexes of M. alternatus were attracted to lures consisting of 2-(undecyloxy)-ethanol combined with the host plant volatiles alpha-pinene and ethanol. A follow-up experiment showed that 2 (undecyloxy)-ethanol was synergized by both ethanol and alpha-pinene. Coupled gas chromatography mass-spectrometry analyses of volatiles sampled from field collected beetles of both sexes revealed that 2-(undecyloxy)-ethanol was a sex specific pheromone component produced only by males. The combination of 2- (undecyloxy) -ethanol with ethanol and/or alpha-pinene will provide a valuable and badly needed tool for quarantine detection, monitoring, and management of M. alternatus. PMID- 22066190 TI - Evaluation of Agrilus planipennis (Coleoptera: Buprestidae) control provided by emamectin benzoate and two neonicotinoid insecticides, one and two seasons after treatment. AB - Effective methods are needed to protect ash trees (Fraxinus spp.) from emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), an invasive buprestid that has killed millions of North American ash (Fraxinus spp.) trees. We randomly assigned 175 ash trees (11.5-48.1 cm in diameter) in 25 blocks located in three study sites in Michigan to one of seven insecticide treatments in May 2007. Treatments included 1) trunk-injected emamectin benzoate; 2) trunk injected imidacloprid; 3) basal trunk spray of dinotefuran with or 4) without Pentra-Bark, an agricultural surfactant; 5) basal trunk spray of imidacloprid with or 6) without Pentra-Bark; or (7) control. Foliar insecticide residues (enzyme-linked immunosorbent assay) and toxicity of leaves to adult A. planipennis (4-d bioassays) were quantified at 3-4-wk intervals posttreatment. Seven blocks of trees were felled and sampled in fall 2007 to quantify A. planipennis larval density. Half of the remaining blocks were retreated in spring 2008. Bioassays and residue analyses were repeated in summer 2008, and then all trees were sampled to assess larval density in winter. Foliage from emamectin benzoate-treated trees was highly toxic to adult A. planipennis, and larval density was < 1% of that in comparable control trees, even two seasons posttreatment. Larval densities in trees treated with trunk-injected imidacloprid in 2007 + 2008 were similar to control trees. Dinotefuran and imidacloprid were effectively translocated within trees treated with the noninvasive basal trunk sprays; the surfactant did not appreciably enhance A. planipennis control. In 2008, larval densities were 57-68% lower in trees treated with dinotefuran or imidacloprid trunk sprays in 2007 + 2008 than on controls, but densities in trees treated only in 2007 were similar to controls. Highly effective control provided by emamectin benzoate for > or = 2 yr may reduce costs or logistical issues associated with treatment. PMID- 22066191 TI - Effectiveness of odor-baited trap trees for plum curculio (Coleoptera: Curculionidae) monitoring in commercial apple orchards in the northeast. AB - The plum curculio, Conotrachelus nenuphar (Herbst), is a key pest of pome and stone fruit in eastern and central North America. For effective management of this insect pest in commercial apple (Malus spp.) orchards in the northeastern United States and Canada, one of the greatest challenges has been to determine the need for and timing of insecticide applications that will protect apple fruit from injury by adults. In a 2004-2005 study, we assessed the efficacy and economic viability of a reduced-risk integrated pest management strategy involving an odor-baited trap tree approach to determine need for and timing of insecticide use against plum curculio based on appearance of fresh egg-laying scars. Evaluations took place in commercial apple orchards in seven northeastern U.S. states. More specifically, we compared the trap-tree approach with three calendar-driven whole-block sprays and with heat-unit accumulation models that predict how long insecticide should be applied to orchard trees to prevent injury by plum curculio late in the season. Trap tree plots received a whole-plot insecticide spray by the time of petal fall, and succeeding sprays (if needed) were applied to peripheral-row trees only, depending on a threshold of one fresh plum curculio egg-laying scar out of 25 fruit sampled from a single trap tree. In both years, level of plum curculio injury to fruit sampled from perimeter-row, the most interior-row trees and whole-plot injury in trap tree plots did not differ significantly from that recorded in plots subject to conventional management or in plots managed using the heat-unit accumulation approach. The amount of insecticide used in trap tree plots was reduced at least by 43% compared with plots managed with the conventional approach. Advantages and potential pitfalls of the bio-based trap tree approach to plum curculio monitoring in apple orchards are discussed. PMID- 22066192 TI - Delaying onion planting to control onion maggot (Diptera: Anthomyiidae): efficacy and underlying mechanisms. AB - Onion maggot, Delia antiqua (Meigen) (Diptera: Anthomyiidae), is an important pest of onion, Allium cepa L., in northern temperate areas, especially in the Great Lakes region of North America Management of D. antiqua relies on insecticide use at planting, but insecticide resistance can cause control failures that threaten the long-term viability of this strategy. Delaying the time onions are planted was investigated as an alternative management approach for D. antiqua and the ecological and behavioral mechanisms underlying host age and insect relationships were examined in laboratory and field experiments. Delaying onion planting by two to four weeks reduced damage to onions by 35 and 90%, respectively. Onions planted later emerged later and this reduced the period overwintered flies had to oviposit on the plants. Moreover, flies tended to lay few to no eggs on these young, late-planted onions. As anticipated, D. antiqua laid 4-8 times more eggs on older onions than on young onions, and older onions were more resilient to injury caused by D. antiqua neonates compared with younger onions. However, the resiliency to maggot attack lessened as the density of D. antiqua increased from 2 to 10 eggs per plant, which probably explains why greater levels of maggot damage are typically observed in early onion plantings compared with later plantings. Delaying onion planting until mid-May reduced D. antiqua damage without jeopardizing the period required to produce marketable yield, but this cultural tactic must be combined with other management strategies to prevent economic loss. PMID- 22066193 TI - Repellency of naturally occurring volatile alcohols to fungus gnat Bradysia sp. nr. coprophila (Diptera: Sciaridae) adults under laboratory conditions. AB - This study, conducted under laboratory conditions, was designed to determine the repellent activity of 10 naturally occurring volatile alcohol constituents against adults of the fungus gnat, Bradysia sp. nr. coprophila (Lintner) (Diptera: Sciaridae). The essential oil constituents were octanoic acid, furfural, acetophenone, benzaldehyde, dimethoxybenzene, borneol, menthol, 1-octen 3-ol, and 7-hydroxycitronellol, and alpha-terpineol. alpha-Terpineol, octanoic acid and furfural were tested at several concentrations, whereas the remaining seven were tested at only one concentration. The essential oil constituents' menthol, 1-octen-3-ol, and borneol displayed the most repellent activity. The mean percentage of fungus gnat adults recovered from the test compound petri dishes associated with the three essential oil constituents was between 6 and 15% compared with between 36 and 50% for the petri dishes with distilled water. The mean +/- SEM number of fungus gnat adults present in the sample compartments associated with menthol (10.4 +/- 2.6), 1-octen-3-ol (18.8 +/- 2.4), and borneol (23.4 +/- 5.6) was statistically lower than those in the petri dishes containing distilled water (60.9 +/- 7.4, 49.8 +/- 4.0, and 79.7 +/- 13.5), respectively. Only the highest concentration of alpha-terpineol (8.0 micromol) displayed significant repellent activity against fungus gnat adults. The other essential constituents tested, including octanoic acid (all three concentrations), furfural (both concentrations), acetophenone, dimethoxybenzene, and 7-hydroxycitronellol, were not statistically different from the distilled water control. The results of this study indicate that certain essential oil constituents repel fungus gnat adults, which may be useful, from a practical standpoint, in deterring adults from laying eggs into growing media. PMID- 22066194 TI - Phenological dynamics of Dasineura mali (Diptera: Cecidomyiidae) and its parasitoid Platygaster demades (Hymenoptera: Platygasteridae) in apple orchards. AB - The midge Dasineura mali Kieffer (Diptera: Cecidomyiidae) is an important pest of apple (Malus domestica Borkh.) and a potential fresh fruit contaminant, causing quarantine concerns. The phenological dynamics of D. mali and its egg parasitoid Platygaster demades Walker (Hymenoptera: Platygasteridae) were studied in the field in Palmerston North, New Zealand, for 2 yr. Both shoot infestation rate by D. mali and D. mali density per shoot sharply increased in the second generation, reaching approximately 65% and 100-200 eggs, respectively. However, although the infestation rate in the third generation remained as high as in the second generation, the pest density per shoot significantly decreased to 40-60 eggs in the third generation. In the fourth generation, both infestation rate and pest density per shoot decreased to approximately 30% and 10 eggs. Due to the simultaneous decline of the apple shoot number and D. mali density in the third and fourth D. mali generations, the absolute number of D. mali in the orchard also has declined proportionally during the same period. The parasitism and superparasitism rates significantly increased as the season progressed, from 45 to 55 and 37% in the first generation to 87 and 82% in the fourth generation, respectively. Our results suggest that P. demades contributes to the continuous decline of D. mali numbers in the field; it is a good searcher, particularly when its hosts become increasingly scarcer over the season, and it avoids overshooting the host population later in the season by increasing superparasitism. The frequency of P. demades aestivation increases from late spring to midsummer and then decreases during the late summer and early autumn. Although the emergence of P. demades was approximately 2 to 3 wk behind that of D. mali in each generation, the increasing parasitism rates from the first to the fourth generations indicate that P. demades is synchronized with D. mali in the field. PMID- 22066195 TI - Chemosterilant bait stations coupled with sterile insect technique: an integrated strategy to control the Mediterranean fruit fly (Diptera: Tephritidae). AB - During 2008 and 2009, the efficacy of the combination of two Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), control techniques, sterile insect technique (SIT) and a chemosterilant bait station system (Adress), was tested in three crops: citrus (Citrus spp.), stone fruit (Prunus spp.), and persimmon (Diospyros spp.). Two thousand sterile males were released per ha each week in the whole trial area (50,000 ha, SIT area). For 3,600 ha, within the whole trial area, 24 Adress traps per ha were hung (SIT + Adress area). Ten SIT + Adress plots and 10 SIT plots in each of three different fruit crops were arranged to assess Mediterranean fruit fly population densities and fruit damage throughout the trial period. To evaluate the efficacy of each treatment, the male and female populations were each monitored from August 2008 to November 2009, and injured fruit was assessed before harvest. Results showed a significant reduction in the C. capitata population in plots treated with both techniques versus plots treated only with the SIT. Likewise, a corresponding reduction in the percentage of injured fruit was observed. These data indicate the compatibility of these techniques and suggest the possibility of using Adress coupled with SIT to reduce C. capitata populations in locations with high population densities, where SIT alone is not sufficiently effective to suppress fruit fly populations to below damaging levels. PMID- 22066196 TI - Rainfastness and residual activity of insecticides to control Japanese beetle (Coleoptera: scarabaeidae) in Grapes. AB - Field-based bioassays and residue profile analysis were used to determine the relative toxicity, rainfastness, and field degradation over time of five insecticides from five insecticide classes on adult Japanese beetles, Popillia japonica Newman (Coleoptera: Scarabaeidae), in grapes, Vitis labrusca L. Bioassays assessed Japanese beetle condition as alive, knockdown, or immobile when exposed for 24 h or 7-d field-aged residues of phosmet, carbaryl, bifenthrin, thiamethoxam, or indoxacarb after 0, 12.7, or 25.4 mm of rain had been simulated. We found that the two most toxic insecticides to Japanese beetle were phosmet and carbaryl, followed by bifenthrin, thiamethoxam, and then indoxacarb. The efficacy of phosmet decreased because of rainfall, but not because of field aging. The efficacy of carbaryl decreased because of rainfall and field aging. The efficacies of bifenthrin and thiamethoxam were not affected by rainfall but decreased because of field aging. The efficacy of indoxacarb was not affected by rainfall or field aging. This study will help vineyard managers make informed decisions on when reapplications of insecticides are needed with the aim of improving integrated pest management programs. PMID- 22066197 TI - Comparative efficacy of plant-derived essential oils for managing ambrosia beetles (Coleoptera: Curculionidae: Scolytinae) and their corresponding mass spectral characterization. AB - Ambrosia beetles (Coleoptera: Curculionidae: Scolytinae) pose a significant challenge to producers of ornamental nursery stock. Conventional insecticides are commonly used for management purposes, but plant-derived essential oils also may discourage ambrosia beetles from initiating attacks. To identify promising commercially available products, field-based efficacy trials were conducted in Ohio in 2009 and 2010 with the following products: Armorex (Soil Technologies), Cinnacure (Proguard, Inc.), EcoTrol (EcoSMART Technologies, Inc.), and Veggie Pharm (Pharm Solutions, Inc.). Potted Magnolia virginiana L. were first injected with 75 ml of 5% ethanol to ensure ambrosia beetle pressure on experimental trees. Mixtures of each product (10% in water) and a water control were applied until runoff and attacks occurring under field conditions were quantified at 1, 4, 7, and 14 d after treatment (DAT). Ambrosia beetle attacks generally increased over time but at differing rates depending on the particular treatment. In 2009, Armorex and Veggie Pharm were associated with the lowest cumulative attacks 14 DAT. In 2010, Armorex and Cinnacure were associated with the fewest attacks 14 DAT. Solid phase microextraction-gas chromatography-mass spectrometry was used to characterize the volatile compounds associated with each product. Allyl isothiocyanate, a compound with known repellent and insecticidal properties, was unique and predominant in Armorex. These experiments identified commercially available botanicals containing plant essential oils with activity against ambrosia beetles, along with demonstrating the usefulness of ethanol-injection to ensure ambrosia beetle pressure under field conditions. Characterizing the constituents of efficacious botanically based products could also lead to the development of improved botanical insecticides. PMID- 22066198 TI - Prevalence of a koinobiont endoparasitoid Misotermes mindeni (Diptera: Phoridae) in colonies of the fungus-growing termite Macrotermes gilvus (Blattodea: Termitidae) in Malaysia. AB - A survey of the infestation rate of colonies of Macrotermes gilvus (Hagen) (Termitidae: Macrotermitinae) with the koinobiont endoparasitoid Misotermes mindeni Disney & Neoh (Diptera: Phoridae) was conducted in Malaysia from September 2009 to January 2011 in the states of Kedah, Penang, Perak, Selangor, Kuala Lumpur, Johor, Terengganu, and Sarawak. Of the 1,125 M. gilvus mounds surveyed, 12.4% contained termites parasitized by M. mindeni and these mounds occurred only in the states of Penang and Perak. High frequencies of mounds containing parasitized termites were found at sites in Penang: Bayan Lepas (21.1%), Minden Campus of Universiti Sains Malaysia ([USM]; 24.5%), Teluk Bahang (28.0%), and Bukit Mertajam (35.0%); the lowest frequency (4.0%) was recorded from Gelugor. The parasitized colonies at all sites were classified as healthy, with exception of several from the Minden Campus of USM (96.4% healthy) and Ayer Itam (87.5% healthy). Most parasitized colonies (71.2%) had a low level of M. mindeni infestation. Only 16.7 and 12.1% of the infested colonies had moderate or high parasite infestation levels, respectively. The height of infected mounds was significantly higher than that of the healthy mounds, but there was no difference between the mound diameters of infested and uninfested mounds. Parasite infestation level was not significantly correlated with mound height or mound diameter. The ambient light intensity at sites with infested mounds was significantly lower than that of uninfested mounds. There was also a significant negative relationship between light intensity and degree of parasitism. PMID- 22066199 TI - Mineral oil and aliphatic alcohols: toxicity and analysis of synergistic effects on German cockroaches (Dictyoptera: Blattellidae). AB - Two mineral oils and 12 linear primary alcohols were studied, alone and in combination, to determine their contact toxicity to adult German cockroaches, Blattella germanica (L.) (Dictyoptera: Blattellidae). The more toxic oil, PD23 (LD50 = 1.45 mg per cockroach) was used for combination studies. Alcohols with carbon chain lengths of C3 and C8 through C12 were the most toxic, with LD50 values ranging from 0.3 to 0.6 mg. C1 (methanol) and C14 (1-tetradecanol) were least toxic, with LD50 values of 2.35 and 1.75 mg, respectively. Eight of the 12 combinations of a nonlethal dose of PD23 oil with an LD10 dose of alcohol produced significantly greater mortality than predicted under the assumption of additive effects. A sample of five synergistic oil + alcohol combinations, covering most of the alcohol carbon chain length range over which synergy occurred, was further studied by calculating LD50 values for three fixed mixture ratios (80:20, 50:50, and 20:80) of each combination. Results were analyzed using both graphical techniques (isobole analysis) and by nonlinear regression. At least one, but not necessarily all, of the three fixed ratio combinations of each oil + alcohol pairing indicated synergy. The conclusions drawn from the isobole and regression analyses were consistent. PMID- 22066200 TI - Reinvasion and colony expansion of Coptotermes formosanus (Isoptera: Rhinotermitidae) after areawide elimination. AB - The population recovery of Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae) colonies were monitored after an areawide elimination of all detectable colonies from September 2003 to August 2005 in Louis Armstrong Park, New Orleans, LA. Six colonies reinvaded the vacant niche created by the full elimination. These colonies expanded their territories throughout the study period. This represented 43% of the original number of colonies present in the park before the elimination. To determine the mode of the reinvasion, nuptial pair establishment was monitored during the C. formosanus dispersal flight seasons. Nuptial pairs were discovered up to 1 yr after the elimination. Morphological and genetic data were collected from field colonies before the full elimination in 2002 and again in 2005 after the reinvasion of these territories by new colonies. These data were used to estimate the relative age of reinvading colonies as compared with their predecessors. It is proposed that the first three reinvading colonies detected were smaller colonies that were undetectable before the full elimination, or were older, established colonies present outside of the park, that expanded their foraging territories into the park in the absence of competition from the eliminated populations. The subsequent three colonies to reinvade seemed to be small colonies founded during or just before the study period by an imago pair after a dispersal flight into the park from outlying areas. The implications of this study on subterranean termite areawide integrated pest management strategies are discussed. PMID- 22066201 TI - Susceptibility of Spodoptera frugiperda (Lepidoptera: Noctuidae) strains from central Colombia to two insecticides, methomyl and lambda-cyhalothrin: a study of the genetic basis of resistance. AB - Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae) is an important pest of several crops in the western hemisphere. This insect has genetically differentiated into two host-associated populations: the corn (Zea mays L.) and the rice (Oryza sativa L.) strains. The corn strain also is found in cotton (Gossypium hirsutum L.) and sorghum and the rice strain in Bermuda grass [Cynodon dactylon (L.) Pers.] and millet. In the United States and Brazil, lines from corn, rice, Bermuda grass, and millet were used to evaluate the resistance of both strains to various insecticides, and found that the corn strain is more resistant than the rice strain. However, in these studies the larvae were not genotyped. In Colombia, genotyping of fall armyworm is necessary because the rice strain also can be found in corn fields. In this work, collected larvae from corn and rice fields from Tolima (central Colombia) were genotyped and evaluated for the resistance to methomyl and lambda-cyhalothrin. We found that the rice strain does not significantly differ in resistance to methomyl compared with the corn strain but it develops tolerance more rapidly to lambda-cyhalothrin. The eggs viability of treated females also was significantly affected by methomyl on each generation. The realized heritability of resistance was higher for lambda cyhalothrin (0.23-0.42) than for methomyl (0.04-0.14). The number of generations needed for 10-fold increase in resistance is approximately 11.5 generations for methomyl and 6.5 for lambda-cyhalothrin. Finally, the genetic basis of resistance to both insecticides involves few recessive autosomal genes. The results obtained here suggest that methomyl is a better option than lambda-cyalothin to control fall armyworm. PMID- 22066202 TI - A multiplex real-time polymerase chain reaction assay to diagnose Epiphyas postvittana (Lepidoptera: Tortricidae). AB - A molecular assay for diagnosis of light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae), in North America is reported. The assay multiplexes two TaqMan real-time polymerase chain reaction (RT-PCR) probe systems that are designed to target DNA segments of the internal transcribed spacer region 2 (ITS2) and 18S rRNA gene. The RT-PCR probe designed for the 18S target recognizes a DNA sequence conserved in all of the moths included in the study and functions as a control in the assay. The second probe recognizes a segment of the ITS2 specifically found in E. postvittana and not found in the other moths included in the study, i.e., this segment is not conserved. Inclusion of the two markers in a single multiplex reaction did not affect assay performance. The assay was tested against 637 moths representing > 90 taxa in 15 tribes in all three subfamilies in the Tortricidae. The assay generated no false negatives based on analysis of 355 E. postvittana collected from California, Hawaii, England, New Zealand, and Australia. Analysis of a data set including 282 moths representing 41 genera generated no false positives. Only three inconclusive results were generated from the 637 samples. Spike experiments demonstrated that DNA contamination in the assay can affect samples differently. Contaminated samples analyzed with the ITS2 RT-PCR assay and DNA barcode methodology by using the cytochrome oxidase I gene can generate contradictory diagnoses. PMID- 22066203 TI - Sequence analysis of the ribosomal internal transcribed spacers region in psocids (Psocoptera: Liposcelididae) for phylogenetic inference and species discrimination. AB - Psocids (Psocoptera: Liposcelididae: Liposcelis spp.) are major pests of stored grain and commonly occur on a wide range of stored products. Increasingly, the genus of Liposcelis has gained recognition of their importance due to their feeding on stored grains, contaminating food, and agricultural commodities as well as transmitting harmful microorganisms, including fungi and bacteria. Psocids have close morphological similarities and often commix occur at the same ecosystems. Therefore, a first step necessary to further implement population studies is the accurate identification of species, based on molecular methods. In this study, we determined nucleotide sequences of the nuclear rDNA internal transcribed spacer (ITS)1-5.8S-ITS2 region in 100 individuals of six Liposcelis species (including Liposcelis bostrychophila Badonnel, Liposcelis entomophila (Enderlein), Liposcelis decolor (Pearman), Liposcelis tricolor Badonnel, Liposcelis paeta Pearman, and Liposcelis yunnaniensis Li & Li) from 16 locations of China. We evaluated the suitability of this marker for phylogenetic inference study in the Liposcelis species. We also developed a molecular identification method for six Liposcelis species based on ITS2 sequence. Results demonstrate that ITS1-5.8S-ITS2 sequences are a useful tool for the population genetic study and phylogeny estimation of Liposcelis species. The results of this study indicate that the ITS2 sequences can be a reliable tool for species discrimination of the six species of psocids tested here. In addition, the multiplex method described proved reliable when tested across different geographical populations. PMID- 22066204 TI - Resistance performances of transgenic bt rice lines T(2A)-1 and T1c-19 against Cnaphalocrocis medinalis (Lepidoptera: Pyralidae). AB - The transgenic Bacillus thuringiensis (Bt) rice, Oryza sativa L., lines T(2A)-1 and T1c-19 expressing Cry2A* and Cry1C* from 'Minhui 63' (MH63) were evaluated for resistance to newly hatched and third-instar larvae of Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), by using detached leaf laboratory bioassays. Both T(2A)-1 and T1c-19 rice showed high C. medinalis resistance; however, the lethal time (LT)50 of larvae fed with T(2A)-1 rice was significantly longer than that of larvae fed with T1c-19 rice, implying T1c-19 rice was more toxic to C. medinalis larvae. Larval mortality after 4 d on nitrogen-free MH63 was 25.5% compared with 2.4% mortality on high nitrogen fertilizer (250 kg N/ha) plants. Larval mortality on high nitrogen T(2A)-1 plants declined by 20% compared with nitrogen-free plants. However, resistance in T1c-19 plants was unaffected by nitrogen fertilizer. C. medinalis moths preferred MH63 at both the seedling and grain milk stages for oviposition but not the T1c-19 and T(2A)-1 Bt rice lines. PMID- 22066205 TI - Distribution and diversity of Russian wheat aphid (Hemiptera: Aphididae) biotypes in South Africa and Lesotho. AB - Russian wheat aphid, Diuraphis noxia (Kurdjumov) (Hemiptera: Aphididae) was recorded for the first time in South Africa in 1978. In 2005, a second biotype, RWASA2, emerged, and here we report on the emergence of yet another biotype, found for the first time in 2009. The discovery of new Russian wheat aphid biotypes is a significant challenge to the wheat, Triticum aestivum L., industry in South Africa. Russian wheat aphid resistance in wheat, that offered wheat producers a long-term solution to Russian wheat aphid control, may no longer be effective in areas where the new biotypes occur. It is therefore critical to determine the diversity and extent of distribution of biotypes in South Africa to successfully deploy Russian wheat aphid resistance in wheat. Screening of 96 Russian wheat aphid clones resulted in identification of three Russian wheat aphid biotypes. Infestations of RWASA1 caused susceptible damage symptoms only in wheat entries containing the Dn3 gene. Infestations of RWASA2 caused susceptible damage symptoms in wheat entries containing Dn1, Dn2, Dn3, and Dn9 resistant genes. Based on the damage-rating scores for the seven resistance sources, a new biotype, which caused damage rating scores different from those for RWASA1 and RWASA2, was evident among the Russian wheat aphid populations tested. This new biotype is virulent to the same resistance sources as RWASA2 (Dn1, Dn2, Dn3, and Dn9), but it also has added virulence to Dn4, whereas RWASA2 is avirulent to this resistance source. PMID- 22066206 TI - Sampling of Cacopsylla pyri (Hemiptera: Psyllidae) and Pilophorus gallicus (Hemiptera: Miridae) in pear orchards. AB - The psyllid Cacopsylla pyri L. (Hemiptera: Psyllidae), is one of the principal pests of pear (Pyrus spp.) orchards and, along with its natural enemies, needs to be carefully monitored for correct integrate pest management and biological pest control decision making. We compare sampling techniques and develop sampling methods for C. pyri and Pilophorus gallicus Remane (Heteroptera: Miridae). Four pear orchards were sampled periodically from 2007 to 2010 in southern Spain by beating branches into funnels or 45-cm-diameter nets and taking shoot samples. Different sampling techniques were compared, and several sampling methods were assayed for adults and nymphs of C. pyri and P. gallicus. Psylla adult and P. gallicus counts in the nets and funnels were similar and closely correlated. Counts of C. pyri adults in the funnels and nets were higher than on shoots, but all measures were closely correlated. The number of nymphs on shoots and leaves was correlated, as were the counts on leaves within shoots. A guide for choosing the sampling unit in cost/precision terms is given. C. pyri nymphs and adults showed an aggregated distribution, whereas P. gallicus had a less-crowded spatial distribution. Enumerative sequential sampling was evaluated for both insects by using the different sampling techniques by resampling experimental data. The negative binomial distribution fitted the experimental data gathered using the different sampling techniques for C. pyri adults and P. gallicus. The use of binomial sampling is discussed for the two insects and the costs involved are compared with those implied in the sequential enumerative method. PMID- 22066207 TI - Spatial associations of insects and mites in stored wheat. AB - The spatial association pattern of insect and mite populations in a steel bin containing stored wheat, Triticum durum Desf., in central Greece, was studied using the Spatial Analysis by Distance IndicEs (SADIE). The monitoring was carried out for 7 mo by using grain trier samples and probe traps. The most abundant insect species were Cryptolestes ferrugineus (Stephens) (Coleoptera: Laemophloeidae) and Plodia interpunctella (Hubner) (Lepidoptera: Pyralidae). For mites, the most abundant species were the phytophagous Lepidoglyphus destructor (Schrank) (Acari: Glycyphagidae) and the predator Blattisocius tarsalis (Berlese) (Mesostigmata: Ascidae). Both for P. interpunctella and C. ferrugineus, trap catches were associated with numbers of individuals in the trier samples, but the overall association index calculated among trap and sample counts was significant only in the 33% of trap-sample pairs of values. Generally, P. interpunctella had the main patch areas in the central part of the bin, with few exceptions, during the entire monitoring period. Similar trends also were noted in the case of C. ferrugineus, which was clearly aggregated in the center of the grain mass. Spatial association maps indicated a stable positive association in the central part of the bin, but in most of the other sampling zones the association was negative. However, distribution of L. destructor, based on trier samples, indicated increased presence in peripheral zones of the grain sampling area. Moreover, B. tarsalis presented the most dispersed distribution among all four species. For each species, the association between two consecutive samplings was significant in the majority of cases, indicating a stable spatial pattern. Finally, B. tarsalis was spatially associated to a higher degree with the insects found rather than with L. desctructor. Moreover, there was no association of insect and mite presence with grain temperature and moisture content. The results of the current study suggest that the coexistence of insects and mites in bulked grain follows a complex pattern, with significant interactions, especially in the case of mite predators, which are spatially associated with insect species. PMID- 22066208 TI - Efficacy of pyriproxyfen for control of stored-product psocids (Psocoptera) on concrete surfaces. AB - The insect growth regulator pyriproxyfen was evaluated as a surface treatment for control of three stored-product psocid pests Liposcelis bostrychophila Badonnel, Liposcelis decolor (Pearman), and Liposcelis paeta Pearman (Psocoptera: Liposcelididae). Nymphs were exposed for 35 d on a concrete surface treated with 2.3 mg of active ingredient/m2 pyriproxyfen. Exposure to pyriproxyfen significantly reduced the numbers of both adults and nymphs in comparison with untreated controls. In adults, the greatest reduction (> 90%) was for L. decolor and L. bostrychophila, whereas for L. paeta it was 49%. Few adults of any species were found in the pyriproxyfen treatments. The greatest numbers of nymphs were recorded for L. bostrychophila for both pyriproxyfen treatments and controls. Few adults of any species were found in the pyriproxyfen treatments. The results indicate that pyriproxyfen is effective for control of L. bostrychophila, L. decolor, and L. paeta on concrete, and although complete control was not achieved, the results warrant further long-term study to determine whether pyriproxyfen can completely eliminate psocid populations over time. PMID- 22066209 TI - Modeling assessment for ammonium nitrogen recovery from wastewater by chemical precipitation. AB - Chemical precipitation to form magnesium ammonium phosphate (MAP) is an effective technology for recovering ammonium nitrogen (NH4(+)-N). In the present research, we investigated the thermodynamic modeling of the PHREEQC program for NH4(+)-N recovery to evaluate the effect of reaction factors on MAP precipitation. The case study of NH4(+)-N recovery from coking wastewater was conducted to provide a comparison. Response surface methodology (RSM) was applied to assist in understanding the relative significance of reaction factors and the interactive effects of solution conditions. Thermodynamic modeling indicated that the saturation index (SI) of MAP followed a polynomial function of pH. The SI of MAP increased logarithmically with the Mg2+/NH4+ molar ratio (Mg/N) and the initial NH4(+)-N concentration (CN), respectively, while it decreased with an increase in Ca2+/NH4+ and CO3(2-)/NH4+ molar ratios (Ca/N and CO3(2-)/N), respectively. The trends for NH4(+)-N removal at different pH and Mg/N levels were similar to the thermodynamic modeling predictions. The RSM analysis indicated that the factors including pH, Mg/N, C(N), Ca/N, (Mg/N)x (CO3(2-)/N), (pH)2, (Mg/N)2, and (C(N))2 were significant. Response surface plots were useful for understanding the interaction effects on NH4(+)-N recovery. PMID- 22066210 TI - Using fluorescence-based microplate assay to assess DOM-metal binding in reactive materials for treatment of acid mine drainage. AB - One potential drawback of compost-based passive bioreactors, which is a promising biotechnology for acid mine drainage (AMD) treatment, is the transport of dissolved organic matter (DOM)-metal complexes in surface waters. To address this problem, the objective of this study was to assess the maximum capacity of organic substrates to release soluble DOM-metal complexes in treated water. The reactivities of DOM in maple wood chips and sawdust, composted poultry manure, and leaf compost were quantified toward Cd2+, Ni2+, Fe2+, and Cu2+ using fluorescence quenching. The DOM showed the highest reactivity toward Fe, but a limited number of available sites for sorption, whereas DOM-Cd complexes exhibited the lowest fluorescence quenching. Overall, the DOM from a mixture of wastes formed higher concentrations of DOM-metal complexes relative to sole substrates. Among DOM-metal complexes, the concentrations of DOM-Ni complexes were the highest. After reaching steady-state, low concentrations of DOM-metal complexes were released in treated water, which is in agreement with theoretical predictions based on geochemical modeling. Therefore, in addition to physicochemical characterization, fluorescence quenching technique is recommended for the substrate selection of bioreactors. PMID- 22066211 TI - Formation of disinfection byproducts in typical Chinese drinking water. AB - Eight typical drinking water supplies in China were selected in this study. Both source and tap water were used to investigate the occurrence of chlorinated disinfection byproducts (DBPs), and seasonal variation in the concentrations of trihalomethanes (THMs) of seven water sources was compared. The results showed that the pollution level for source water in China, as shown by DBP formation potential, was low. The most encountered DBPs were chloroform, dichloroacetic acid, trichloroacetic acid, and chlorodibromoacetic acid. The concentration of every THMs and haloacetic acid (HAA) compound was under the limit of standards for drinking water quality. The highest total THMs concentrations were detected in spring. PMID- 22066212 TI - Distribution and origin of polycyclic aromatic hydrocarbons in surface sediments from an urban river basin at the Metropolitan region of Curitiba, Brazil. AB - The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) were determined in surface sediment samples from nine sites located at the Iguacu River Basin in the Metropolitan Region of Curitiba, Brazil to evaluate their distribution and sources. The total concentration of the PAHs was greater for sediments from highly urbanized areas, while the sediments from the Irai Environmental Protection Area (Irai EPA) showed significantly low concentrations. The sediments from the Iguacu and Barigui rivers were classified as highly contaminated, while those from the Cercado and Curralinho rivers were classified as moderately contaminated. The predominance of PAHs containing two to four aromatic rings in most of the samples suggested the direct input of raw sewage into the water resources evaluated. Benzo[g,h,i]perylene, dibenzo[a,h]anthracene and indeno[1,2,3-cd]pyrene were predominant in sediments from the areas under the greatest urban and industrial development. The correlation between thermodynamic stability and the kinetics of evolution presented by the isomeric pairs indicated that combustion is the predominant source of PAHs in the sediments because the combustion of fossil fuels affected most of the points evaluated, followed by combustion of biomass and eventually combustion of oil product inputs. In general, the results showed that areas under strong urban influence, as well as the Irai EPA, receive contributions of PAHs from similar sources. PMID- 22066213 TI - Effect of dissolved organic matter on mercury release from water body. AB - Dissolved organic matter (DOM) plays an important role in the process of mercury release from water body. In this study, the influence of DOM from different sources (DOM(R), DOM(S) and DOM(H), extracted from rice straw, compost and humic soil respectively) on mercury reduction was investigated. The molecular weight distribution and chemical composition of DOM from each source were determined using ultrafiltration membrane technique and elemental analysis respectively. The result showed that mercury release from DOM-added samples was much lower than the control; the lowest mercury release flux was observed in the treatment of DOM(H), 25.02% of the control, followed by DOM(S) and DOM(R), 62.46% and 64.95% of the control, respectively. The higher saturation degree and lower molecular weight of DOM(H) was responsible for the highest inhibition degree on the mercury release. The link between DOM(H), concentration and mercury flux was also estimated and the result showed that mercury flux was increased with DOM(H) at lower concentration, while decreased with DOM(H) at higher concentration. Different mechanism dominated the influence of DOM on mercury release with variation of DOM concentration. PMID- 22066214 TI - Kappaphycus alvarezii waste biomass: a potential biosorbent for chromium ions removal. AB - The Cr(III) sorption experiments onto Kappaphycus alvarezii waste biomass were conducted at different pH values (2-6) under the conditions of initial metal concentration of 10-50 mg/L and the chemical compositions of Cr-Cu and Cr-Cd. The Cr(III) sorption capacities were slightly dependent on pH, and the maximum sorption capacity was 0.86 mg/g at pH 3. The sorption capacities increased with increase in the initial metal concentration, whereas it was suppressed by the presence of Cu(II) and Cd(III) in the solution. The Cr(III) sorption equilibrium was evaluated using Langmuir, Freundlich and BET isotherms. The sorption mechanisms were characterised using scanning electron microscopy and Fourier transform infrared spectroscopy. The main mechanisms were ion exchange coupled with a complexation mechanism. Kappaphycus alvarezii waste biomass represents a potential for Cr(III) ion removal from aqueous solution. PMID- 22066215 TI - Stepwise superposition approximation approach for analytical solutions with non zero initial concentration using existing solutions of zero initial concentration in contaminate transport. AB - Analytical solutions for contaminant transport are widely used for both theoretical and practical purposes. However, many existing solutions are obtained subject to an initial condition of zero concentration, which is often unrealistic in many practical cases. This article proposed a stepwise superposition approximation approach to solve the non-zero initial concentration problem for first-type and third-type boundary conditions by using the existing zero initial concentration solution. Theoretical examples showed that the approach was highly efficient if a proper superposition scheme with relative concentration increments was constructed. The key parameter that controlled the convergence speed was the time increment (lambdat) multiplied by the rate constant (lambda). The approach served also as an alternative way to make a convenient concentration calculation even if the non-zero initial concentration solution of a problem was known. PMID- 22066216 TI - Application of the AERMOD modeling system for environmental impact assessment of NO2 emissions from a cement complex. AB - We applied the model of American Meteorological Society-Environmental Protection Agency Regulatory Model (AERMOD) as a tool for the analysis of nitrogen dioxide (NO2) emissions from a cement complex as a part of the environmental impact assessment. The dispersion of NO2 from four cement plants within the selected cement complex were investigated both by measurement and AERMOD simulation in dry and wet seasons. Simulated values of NO2 emissions were compared with those obtained during a 7-day continuous measurement campaign at 12 receptors. It was predicted that NO2 concentration peaks were found more within 1 to 5 km, where the measurement and simulation were in good agreement, than at the receptors 5 km further away from the reference point. The Quantile-Quantile plots of NO2 concentrations in dry season were mostly fitted to the middle line compared to those in wet season. This can be attributed to high NO2 wet deposition. The results show that for both the measurement and the simulation using the AERMOD, NO2 concentrations do not exceed the NO2 concentration limit set by the National Ambient Air Quality Standards (NAAQS) of Thailand. This indicates that NO2 emissions from the cement complex have no significant impact on nearby communities. It can be concluded that the AERMOD can provide useful information to identify high pollution impact areas for the EIA guidelines. PMID- 22066217 TI - Emissions of C2 - C12 hydrocarbons in the Hsuehshan tunnel, Taiwan. AB - The concentrations of 56 hydrocarbons from C2 to C12 were measured simultaneously in the southbound bore, the northbound bore and the exhaust air shafts of the Hsuehshan tunnel near Yilan, Taiwan for 12 days during 2007 and 2008. A total of 60 integrated air samples were collected using stainless steel canisters and analyzed using GC/FID and GC/MS. The five most abundant species in all samples were ethylene, acetylene, isopentane, propylene and toluene. The exit/entrance ratios of total non-methane hydrocarbons (NMHC) concentration were 7.8 and 4.8 for the southbound and northbound bores, respectively. Furthermore, the exhaust from the vertical shafts affects air quality in the neighborhood. The most abundant species of emission rate (ER) was toluene (21.93-42.89 mg/sec), followed by isopentane, ethylene, propylene and 1-butene, with ER ranging from 2.50 to 9.31 mg/sec. The species in the three exhaust air shafts showed that the reactivities of these emissions are similar to those of vehicle emissions. Notably, the control of emissions in the vertical shafts of the vehicle tunnel will be important in the future. PMID- 22066218 TI - Forest soil CO2 fluxes as a function of understory removal and N-fixing species addition. AB - We report on the effects of forest management practices of understory removal and N-fixing species (Cassia alata) addition on soil CO2 fluxes in an Eucalyptus urophylla plantation (EUp), Acacia crassicarpa plantation (ACp), 10-species-mixed plantation (Tp), and 30-species-mixed plantation (THp) using the static chamber method in southern China. Four forest management treatments, including (1) understory removal (UR); (2) C. alata addition (CA); (3) understory removal and replacement with C. alata (UR+CA); and (4) control without any disturbances (CK), were applied in the above four forest plantations with three replications for each treatment. The results showed that soil CO2 fluxes rates remained at a high level during the rainy season (from April to September), followed by a rapid decrease after October reaching a minimum in February. Soil CO2 fluxes were significantly higher (P < 0.01) in EUp (132.6 mg/(m2 x hr)) and ACp (139.8 mg/(m2 x hr)) than in Tp (94.0 mg/(m2 x hr)) and THp (102.9 mg/(m2 x hr)). Soil CO2 fluxes in UR and CA were significantly higher (P < 0.01) among the four treatments, with values of 105.7, 120.4, 133.6 and 112.2 mg/(m2 x hr) for UR+CA, UR, CA and CK, respectively. Soil CO2 fluxes were positively correlated with soil temperature (P < 0.01), soil moisture (P < 0.01), NO3(-)-N (P < 0.05), and litterfall (P < 0.01), indicating that all these factors might be important controlling variables for soil CO2 fluxes. This study sheds some light on our understanding of soil CO2 flux dynamics in forest plantations under various management practices. PMID- 22066219 TI - Nitrogen cycle of a typical Suaeda salsa marsh ecosystem in the Yellow River estuary. AB - The nitrogen (N) biological cycle of the Suaeda salsa marsh ecosystem in the Yellow River estuary was studied during 2008 to 2009. Results showed that soil N had significant seasonal fluctuations and vertical distribution. The N/P ratio (15.73 +/- 1.77) of S. salsa was less than 16, indicating that plant growth was limited by both N and P. The N absorption coefficient of S. salsa was very low (0.007), while the N utilization and cycle coefficients were high (0.824 and 0.331, respectively). The N turnover among compartments of S. salsa marsh showed that N uptake from aboveground parts and roots were 2.539 and 0.622 g/m2, respectively. The N translocation from aboveground parts to roots and from roots to soil were 2.042 and 0.076 g/m2, respectively. The N translocation from aboveground living bodies to litter was 0.497 g/m2, the annual N return from litter to soil was far less than 0.368 g/m2, and the net N mineralization in topsoil during the growing season was 0.033 g/m2. N was an important limiting factor in S. salsa marsh, and the ecosystem was classified as unstable and vulnerable. S. salsa was seemingly well adapted to the low-nutrient status and vulnerable habitat, and the nutrient enrichment due to N import from the Yellow River estuary would be a potential threat to the S. salsa marsh. Excessive nutrient loading might favor invasive species and induce severe long-term degradation of the ecosystem if human intervention measures were not taken. The N quantitative relationships determined in our study might provide a scientific basis for the establishment of effective measures. PMID- 22066220 TI - Desulfurization of dibenzothiophene (DBT) by a novel strain Lysinibacillus sphaericus DMT-7 isolated from diesel contaminated soil. AB - A new bacterial strain DMT-7 capable of selectively desulfurizing dibenzothiophene (DBT) was isolated from diesel contaminated soil. The DMT-7 was characterized and identified as Lysinibacillus sphaericus DMT-7 (NCBI GenBank Accession No. GQ496620) using 16S rDNA gene sequence analysis. The desulfurized product of DBT, 2-hydroxybiphenyl (2HBP), was identified and confirmed by high performance liquid chromatography analysis and gas chromatography-mass spectroscopy analysis respectively. The desulfurization kinetics revealed that DMT-7 started desulfurization of DBT into 2HBP after the lag phase of 24 hr, exponentially increasing the accumulation of 2HBP up to 15 days leading to approximately 60% desulfurization of the DBT. However, further growth resulted into DBT degradation. The induced culture of DMT-7 showed shorter lag phase of 6 hr and early onset of stationary phase within 10 days for desulfurization as compared to that of non-induced culture clearly indicating the inducibility of the desulfurization pathway of DMT-7. In addition, Lysinibacillus sphaericus DMT 7 also possess the ability to utilize broad range of substrates as sole source of sulfur such as benzothiophene, 3,4-benzo DBT, 4,6-dimethyl DBT, and 4,6-dibutyl DBT. Therefore, Lysinibacillus sphaericus DMT-7 could serve as model system for efficient biodesulfurization of diesel and petrol. PMID- 22066221 TI - Levels of synthetic musk fragrances in human milk from three cities in the Yangtze River Delta in Eastern China. AB - Synthetic musks are used as additives in many household products. After absorption into the human body, they accumulate and their concentrations in human milk reflect both the mother and her infant's exposure level. Concentrations of four synthetic musks, musk xylene (1-tert-butyl-2,6-dimethyl-2,4,6 trinitrobenzene, MX), musk ketone (4-tert-butyl-2,6-dimethyl-3,5 dinitroacetophenone, MK), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8 hexamethylcyclopenta[gamma]-2-benzopyran (HHCB) and 7-acetyl-1,1,3,4,4,6 hexamethyl- 1,2,3,4-tetrahydronaphthalene (AHTN), were determined in human milk samples collected from Shanghai, Wuxi, and Shaoxing in Eastern China. The four synthetic musks were found in most samples analyzed, with HHCB the dominant component followed by MX. The median (mean) values for HHCB, AHTN, MX and MK concentrations were 63 (82), 5 (12), 17 (24) and 4 (9) ng/g lipid weight, respectively. These data suggested the total synthetic musk contamination was low, and the distribution percentage was HHCB > MX > AHTN approximately MK. The relative high ratio of nitro to polycylic musk indicated that nitro musks were still widely used. The musk concentrations in these cities were not significantly different from each other (p > 0.05). Principal components score plots were obtained, which showed similar exposure sources. The amount of total synthetic musks in human milk were not associated with mother's age, although HHCB was significantly correlated with AHTN (p < 0.05). Daily ingestion of HHCB, AHTN, MX and MK for infants from human milk were estimated as (2526 +/- 2926), (370 +/- 524), (7391 +/- 832), and (277 +/- 462) ng/day, respectively. Those doses were 1 2 orders of magnitude below the provisional tolerable daily intakes. PMID- 22066222 TI - Comparative study of heavy metal and pathogenic bacterial contamination in sludge and manure in biogas and non-biogas swine farms. AB - The objective of this study is to determine and compare the heavy metal (Zn, Cu, Cd, Pb) and bacterial (E. coli, coliform and Salmonella spp.) contamination between swine farms utilizing biogas and non-biogas systems in the central part of Thailand. Results showed that average levels of E. coli, coliform, BOD, COD, Zn, Cu and Pb in sludge from the post-biogas pond were higher than the standard limits. Moreover, the levels of E. coli, coliform, Cd and Pb were also higher than the standard limits for dry manure. The levels of E. coli, coliform and BOD on biogas farms were lower than on non-biogas farms. Following isolation of Salmonella spp., it was found that Salmonella serovars Rissen was the most abundant at 18.46% (12/65), followed by Anatum 12.31% (8/65), and Kedougou 9.23% (6/65). The pathogenic strains of Salmonella serovars Paratyphi B var. java and Typhimurium were present in equal amounts at 4.62% (3/65) in samples from all swine farms. This study revealed that significant reduction in E. coli and coliform levels in sludge from covered lagoon biogas systems on swine farms. The presence of Salmonella as well as Cd and Pb, in significant amount in dry manure, suggests that there is a high probability of environmental contamination if it is used for agricultural purposes. Thus, careful waste and manure disposal from swine farms and the regular monitoring of wastewater is strongly recommended to ensure the safety of humans, other animals and the environment. PMID- 22066223 TI - Photoelectrochemical degradation of Methylene Blue with beta-PbO2 electrodes driven by visible light irradiation. AB - Beta-PbO2 electrodes were prepared by electro-deposition and characterized by scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and linear sweep voltammetry. We confirmed pure (beta-PbO2 crystals were on the electrode and it had a high oxygen evolution potential. The photoactivity and photoelectrochemical (PEC) properties of the beta-PbO2 electrode were investigated under visible light irradiation (lambda > 420 nm) for the decolorization of Methylene Blue. Pseudo first-order kinetics parameter (K(app)) for dye decolorization using the beta-PbO2 electrode achieved 6.71 x 10( 4) min(-1) under visible light irradiation, which indicated its excellent visible light-induced photoactivity. The K(app) of the PEC process was as much as 1.41 x 10(-3) min(-1) and was 1.71 times that of visible light irradiation or electrolysis even in the presence of the beta-PbO2 electrode. A significant synergetic effect was observed in the PEC system. We also employed TiO2 modified beta-PbO2 electrodes in this test, which revealed that the TiO2 immobilized on the beta-PbO2 electrode inhibited the visible light-induced PEC efficiency despite the amount of TiO2 used for electrode preparation. The beta-PbO2 electrode was also superior to the dimensionally stable anode (Ti/Ru(0.3)Ti(0.7)O2) in visible light-induced photoactivity and PEC efficiency. PMID- 22066224 TI - Combining material characterization with single and multi-oxyanion adsorption for mechanistic study of chromate removal by cationic hydrogel. AB - Cationic hydrogel with magnetic property was synthesized via radical polymerization and its removal capacity of chromate from contaminated water was found to be 200 mg/g. Using Fourier transform infrared spectroscopy (FT-IR) study, the mechanism of chromate removal by hydrogel was found to be non-specific adsorption, mainly due to ion exchange, as evidenced by the positively charged functional group, trimethyl ammonium -N+(CH3)3, in the monomer. Verifications were accordingly determined by testing different oxyanion adsorption onto the hydrogel. The results of the chromate adsorption experiments illustrated that the amount of chromate adsorbed was nearly equal to that of the chloride released from the hydrogel, which is part of the evidence for ion exchange. Single and multi-oxyanion adsorption experiments were also performed, and it was demonstrated that ion removal was species independent, but charge dependent, another characteristic of the ion exchange process. It was found that the same Langmuir model can be applied to best fit the findings of single and multi oxyanion adsorption, which further indicates the mechanism of chromate removal is attributed to ion exchange. In view of the above, the background anions compete for adsorption sites with chromate, evidenced by inhibitive chromate removal in the presence of background electrolytes in the batch studies, further echoing the ion exchange mechanism. PMID- 22066225 TI - N2O and NH3 emissions from a bioreactor landfill operated under limited aerobic degradation conditions. AB - The combination of leachate recirculation and aeration to landfill may be an efficient way for in-situ nitrogen removal. However, nitrogenous substances contained in the landfill layer are concomitantly transformed into N2O and NH3, leading to increased emissions into the atmosphere. In the present study, the emissions of N2O and NH3 were measured under conditions of fresh or partially stabilized refuse with or without leachate recirculation or intermittent aeration. The results showed that the largest N2O emission (12.4 mg-N/L of the column) was observed in the aerated column loaded with partially stabilized refuse and recycled with the leachate of low C/N ratio; while less than 0.33 mg N/L of the column was produced in the other columns. N2O production was positively correlated with the prolonged aerobic time and negatively related with the C/N ratio in the recycled leachate. NH3 volatilization increased with enhanced gas flow and concentration of free ammonia in the leachate, and the highest cumulative volatilization quantity was 1.7 mg-N/L of the column. PMID- 22066226 TI - Application of waste frying oils in the biosynthesis of biodemulsifier by a demulsifying strain Alcaligenes sp. S-XJ-1. AB - Exploration of biodemulsifiers has become a new research aspect. Using waste frying oils (WFOs) as carbon source to synthesize biodemulsifiers has a potential prospect to decrease production cost and to improve the application of biodemulsifiers in the oilfield. In this study, a demulsifying strain, Alcaligenes sp. S-XJ-1, was investigated to synthesize a biodemulsifier using waste frying oils as carbon source. It was found that the increase of initial pH of culture medium could increase the biodemulsifier yield but decrease the demulsification ratio compared to that using paraffin as carbon source. In addition, a biodemulsifier produced by waste frying oils and paraffin as mixed carbon source had a lower demulsification capability compared with that produced by paraffin or waste frying oil as sole carbon source. Fed-batch fermentation of biodemulsifier using waste frying oils as supplementary carbon source was found to be a suitable method. Mechanism of waste frying oils utilization was studied by using tripalmitin, olein and tristearin as sole carbon sources to synthesize biodemulsifier. The results showed saturated long-chain fatty acid was difficult for S-XJ-1 to utilize but could effectively enhance the demulsification ability of the produced biodemulsifier. Moreover, FT-IR result showed that the demulsification capability of biodemulsifiers was associated with the content of C=O group and nitrogen element. PMID- 22066227 TI - Voltammetric response of ferroceneboronic acid to diol and phenolic compounds as possible pollutants. AB - A voltammetric determination of possible organic pollutants such as diol and phenolic compounds in water was studied using ferroceneboronic acid (FBA) as a redox-active marker. A cyclic voltammogram of FBA exhibited a pair of oxidation and reduction peaks at 230 and 170 mV at pH 7.0, respectively, while another pair of redox peaks was observed in the presence of diol or phenolic compounds tested. The results were rationalized based on the formation of boronate esters of FBA with the added compounds. The changes in the redox peak currents were dependent on the concentration of the additives, suggesting a usefulness of FBA in the electrochemical determination of these compounds in water. PMID- 22066228 TI - Effect of manufacturing methods of AgCl/Al2O3 catalyst on selective catalytic reduction of NO(x). AB - The AgCl/Al2O3 catalyst has potential for use in the selective catalytic reduction (SCR) of NO(x). A compound hydrocarbon, following oxygenation is used as a type of reducing agent. In this experiment, the AgCl/Al2O3 catalyst was produced by four different methods, and the differences among their reduction catalysis of NO(x) were compared. Ethanol was used as a type of reducing agent. X ray diffraction analysis was performed to study the crystalline structure and scanning electron microscope and transmission electron microscope (TEM) were applied to determine the microindentation. The results indicated that, in the range of 350-400 degrees C, there was no significant difference on the NO(x) reduction rate; however, there was dispersion at high and low temperature ranges. The size of the AgCl particles was about 20-100 nm. PMID- 22066229 TI - Tyrosinase-modified carbon felt-based flow-biosensors: the role of ultra sonication in shortening the enzyme immobilization time and improving the sensitivity for p-chlorophenol. AB - Tyrosinase (TYR) was covalently immobilized onto amino-functionalized carbon felt surface via glutaraldehyde-coupling under ultrasonic treatment for 10 min. The resulting TYR-immobilized carbon felt was used as a working electrode unit of bioelectrocatalytic flow-through detector for TYR substrates (catechol, p chlorophenol (p-CP), p-cresol, phenol etc.). Cathodic peak currents based on the electroreduction of enzymatically produced o-quinones were detected at -50 mV vs. Ag/AgCl. Compared with previous work in which TYR was immobilized onto amino functionalized carbon felt for 16 hr without the ultrasonic treatment, we succeeded in (1) shortening the enzyme immobilization time from 16 hr to 10 min, (2) enhancing the sensitivity of p-CP, and (3) improving the operational stability of p-CP. The ultrasonic treatment during the TYR immobilization step would lead to certain changes in the structure of the immobilized TYR and the morphology of the immobilized TYR-layer on the carbon felt surface. PMID- 22066230 TI - Mineralization of aqueous pentachlorophenolate by anodic contact glow discharge electrolysis. AB - Exhaustive mineralization of pentachlorophenolate ion (PCP) in phosphate buffer was carried out using anodic contact glow discharge electrolysis (CGDE), in which plasma was sustained between the electrolyte and anode. During CGDE, PCP degraded smoothly. The amount of total organic carbon decreased significantly, indicating the eventual conversion of the carbon atoms of benzene nucleus to inorganic carbons. Furthermore, chlorine atoms in PCP were liberated as chloride ions. As a primary intermediate product, 2,3,5,6-tetrachloro-1,4-benzoquinone was detected, and oxalate and formate as byproducts were also found. It was revealed that disappearance of PCP obeyed first-order kinetics. The reaction rate was generally unaffected by both O2 and inert gases in the cell, although it decreased by raising initial pH of solution. In addition, a plausible reaction pathway involving hydroxyl radical was proposed. PMID- 22066231 TI - Electropolymerized poly(Toluidine blue)-modified carbon felt for highly sensitive amperometric determination of NADH in flow injection analysis. AB - Poly(pheniothiazine) films were prepared on a porous carbon felt (CF) electrode surface by an electrooxidative polymerization of three phenothiazine derivatives (i.e.,Tthionine (TN), Toluidine Blue (TB) and Methylene Blue (MB)) from 0.1 mol/L phosphate buffer solution (pH 7.0). Among the three phenothiazies, the poly(TB) film-modified CF exhibited an excellent electrocatalytic activity for the oxidation of nicotinamide adenine dinucleotide reduced form (NADH) at +0.2 V vs. Ag/AgCl. The poly(TB) film-modified CF was successfully used as working electrode unit of highly sensitive amperometric flow-through detector for NADH. The peak currents (peak heights) were almost unchanged, irrespective of a carrier flow rate ranging from 2.0 to 4.1 mL/min, resulting in the measurement of NADH (ca. 30 samples/hr) at 4.1 mL/min. The peak current responses of NADH showed linear relationship over the concentration range from 1 to 30 micromol/L (sensitivity: 0.318 microA/(micromol/L); correlation coefficient: 0.997). The lower detection limit was found to be 0.3 micromol/L (S/N = 3). PMID- 22066232 TI - [Characteristics of hydronephrosis due to obstruction of the pyeloureteral segment combined with dorsal rotation of the kidney]. AB - Rotation of the kidney is caused by its dystopia and abnormal blood circulation. Dorsal rotation of the kidney in normal position is a rare anomaly. We studied a clinical course, evidence obtained at renosonography, excretory urography, computed tomography, radionuclide investigation, anatomic variants of pyeloureteral segment obstruction in female patients with right-side hydronephrosis in the presence of dorsal rotation of the kidney before and after pyeloplasty. We made pyeloplasty for obstruction of the pyeloureteral segment in 266 patients in 2001-2009. Hydronephrosis was accompanied with dorsal rotation of the kidney in 21 (7.9%) cases. Surgical approaches to the pelviureteral segment are characterized. The dorsal approach is a good alternative to standard subcostal approach, provides good visualization in creation of anastomosis, significantly reduces distance from the skin cut to pyeloureteral segment and offers the best cosmetic result. In subcostal approach mobilization of the pelvis and pyeloureteral segment is preferable on the posterior surface of the kidney. A laparoscopic transperitoneal approach is not justified as it implies wide mobilization of the kidney, the anastomosis is created in extremely limited space. PMID- 22066233 TI - [Efficacy of uro-vaxom in recurrent infectious-inflammatory diseases of the urogenital system]. AB - Our study prospects of urovaxom in improvement of efficacy and prevention of recurrent urogenital infection. One capsule of oral vaccine uro-vaxom was given daily for a month to 127 patients: 23 males with chronic bacterial prostatitis/urethroprostatitis, 75 females with chronic cystitis, 29 females with urolithiasis complicated with secondary chronic pyelonephritis. Control examination was made each two months for a year. In signs of inflammation the patients received one more course of uro-vaxom for a month. It was followed by control examinations each three month for a year. We observed a 6-12 month "cold" period after one course of uro-vaxom in 86.7% patients. After the second course of immunoprophylaxis recurrent urogenital infection occurred 8 times less often. Thus, immunoprophylaxis of urogenital infection with oral vaccine uro-vaxom is highly effective, is well tolerated and, therefore, must enter the standards of medical care for patients with urogenital infection. PMID- 22066234 TI - [Choice of an optimal free graft for replacement urethroplasty in extensive urethral strictures]. AB - Irrespective of the type and properties of a free graft in urethroplasty, survival of the graft depends on blood circulation in the nutrient bed. We made an experimental trial to study engraftment of free grafts of buccal and lingual mucosa on different types of the nutrient bed. Free flaps (78 buccal and 86 lingual mucosa samples) were taken from 52 male Wistar rats (300 to 470 body mass). Grafting was made on different types of nutrient bed - skeletal muscle, subcutaneous fat and penile tunica albuginea. Histological examination of the grafts was made 2, 4, 7 and 14 days after transplantation. The process of engraftment followed all the stages of nonspecific inflammation. The alteration stage (48 hours) is characterized by marked epithelial atrophy, necrosis of most of the cross-striate muscular fibers of the graft, necrotic alterations of the nutrient bed, primarily in the suture area. Excudation and emigration (2-4 days)- by continued necrotic changes with infiltration of the graft with neutrophilic leukocytes, edema of the upper layer stroma and infiltrate extention on the nutrient bed. Proliferation (day 7)--by attenuation of necroinflammatory processes, decline of leukocyte infiltration, formation of blood vessels in the subepithelial base of the graft. Regeneration (day7-14)--by recovery of the epithelial graft layer, development of granulation tissue in the submucosal base. The best engraftment was registered on transplantation on penile tunica albuginea (buccal graft--93.4%, lingual one--88.9%). Successful implantation on the muscle occurred in 90.7% for buccal and 87.9% for lingual grafts. On fat tissue buccal transplant failed in 19, lingua--in 23.89% transplantations. Thus, staging in interaction between different grafts and types of nutrient bed do not depend on characteristics of the bed and graft. Necroinflammatory changes in the buccal graft change for proliferative processes earlier than in the lingual one. Proliferative and regenerative processes develop earlier on penile tunica albuginea. Alteration and exudation are more pronounced on subcutaneous fat. PMID- 22066235 TI - [Mini-invasive operations for correction of urinary incontinence in females]. AB - We compared efficacy of surgical treatment of urinary incontinence in women depending on the size of the synthetic sling and technique of its installation. From January to September 2009 we made 75 operations with synthetic suburethral slings: TVT-SECUR (TVT-S)--group 1 (n = 35) and TVT-O- group 2 (n = 40). The sling was installed in U position in 14 patients of group 1 and in H position in 21 patients. The control examinations included questionnaire survey, cough stress test (in bladder volume more than 150 ml), vaginal investigation, uroflowmetry, in urgency--complex urodynamic examination. A total of 32 patients of group 1 and 40 patients of group 2 were examined postoperatively. A positive result was achieved in 20 (62%) and 38 (95%) (p = 0.0006) patients of group 1 and 2, respectively. Quality of life was assessed as good and very good by 22 (68%) and 37 (93%) patients of groups 1 and 2 (p = 0.0105), respectively. The control examination after 6 months of follow-up showed good result in 7 (53%) and 13 (68%) patients of group 1 (subgroups U and H, respectively). Reoperation for urinary incontinence was made in 4 (30%) patients of subgroup U and 1 (5%)--of subgroup H. Thus, surgical treatment of urinary incontinence in women according to TVT-0 technique is more effective than in TVT-S surgery, but minisling TVT-S is more effective in patients with bad somatic status and in H position. PMID- 22066236 TI - [Combined lumbosacral and vaginal physiotherapy in the treatment of overactive bladder in postmenopausal women]. AB - Efficacy of combined application of physical factors including lumbosacral magnetotherapy and vaginal vibromagnetic impact is shown in 48 postmenopausal women (mean age 62.5 +/- 1.6 years) with overactive bladder (OAB). Choice of this combination is explained by a multifactorial OAB pathogenesis and degenerative spinal diseases often encountered in postmenopausal women (70.8% in this study). The exposures of the spine and the bladder (vaginal) were made one after the other with duration of the first stage 10-15 min, of the second--5-7 min, the course consisted of 10-12 procedures. The results of the treatment were assessed by urination rhythm, volume, number of incontinence episodes. Quality of life was evaluated according to special questionnaires. Trophic function of the spinal cord and innervation of the bladder were studied by n. tibialis conduction measured by electroneuromyography (ENMG). The following results were obtained: reduction of urinations for 24 hours by 36.9%, urgent episodes--by 44%, urgent incontinence--by 59.7%. Voiding volume significantly increased (by 26%). A total score of anxiety related to OAB fell by 51.3%. M-response amplitude in ENMG rose 1.5-fold, while velocity of the impulse conduction along the n. tibialis enhanced 1.2-fold. The technique was accomplished with AMUS-01-Intramag device and attachment to it Rectomassager made in Russia. PMID- 22066237 TI - [Using zidena in the treatment of erectile dysfunction associated with stress induced arterial hypertension in workers of locomotive teams]. AB - Thirty train drivers with erectile dysfunction (ED) and arterial hypertension were examined : physical examination, blood count, urinalysis, penile laser Doppler flowmetry (LDF). ED severity was assessed by Loran-Segal questionnaire of male copulative function (MCF) and international index of erectile function (IIEF). Zidena was used in a dose 100 mg 30 min before coitus twice a weak. Examinations have detected mild and moderate ED, spastic disorders of penile microcirculation. MCF significant improvement (p < 0.05), rise of IIEF score were seen after 30 days of zidena treatment. A positive trend was observed after 15 days of treatment. LDF registered a significant (p < 0.05) improvement of microcirculation. Tissue hypoxia and ischemia lowered, blood inflow in the system of microcirculation increased. A passive mechanism of blood flow regulation, vasodilation almost corresponded to physiological standards. Administration of zidena in patients with stress-induced hypertension has improved libido, quality and duration of erection, penile microcirculation due to better tissue perfusion with blood, reduction of ischemia and blood congestion in the venules. Duration of coitus increased. PMID- 22066238 TI - [Correction of complement system failure in patients with chronic prostatitis]. AB - The aim of the study was detection of local and systemic changes in the complement system in patients with chronic abacterial prostatitis (CAP) and chronic bacterial prostatitis (CBP) and to assess a relevant corrective efficacy of the hardware and software complex Andro-Gin (KAP-ELM-01 Andro-Gin). Before treatment, blood plasma of CAP patients contained elevated concentrations of all studied components of the compliment system and factor H but subnormal concentration of C1-inhibitor. Locally, all the compliment indices were high including C1-inhibitor and factor H except component C5. Initial blood plasma compliment fractions in CBP patients were elevated but regulatory proteins concentrations were low. Local compliment components C3, C4, C5 and C5a and factor H were significantly higher. Standard treatment of CAP partially corrected the level of C3, C3a, C4 components, locally normalized concentration of C3 component and corrected C4 component, while in CBP standard treatment normalized concentration of C3 component and reduced C3a, C4, C5 and C5a components, locally normalized the levels of C3, C4 components, corrected concentration of C3a, C5, C5a components, raised regulatory factors. Combination of the standard treatment with Andro-Gin unit compared to standard treatment alone, in CAP corrected plasma concentrations of C3, C3a, C4 compliment components and significantly raised levels of regulatory factors, locally--partially normalized the level of factor H. In CBP additional use of Andro-Gin more significantly improved concentrations of C3a and C5a components , locally--C5a component, raised significantly concentration of regulatory factors C1-inhibitor and factor H. Thus, KAP-ELM-01 Andro-Gin administration in CAP and CBP patients promotes more effective correction of systemic and local disorders in the compliment system, the improvement being more pronounced in CBP. PMID- 22066239 TI - [Current approaches to the treatment of non-gonococcal urethritis in men]. AB - The study was made of 50 men suffering from non-gonococcal urethritis caused by mixed pathogenic and opportunistic urogenital infection. Clinical characteristics of urethritis in relation to infection pathogen are shown. The results of clinical and laboratory examinations were considered in choice of antibacterial therapy. Safocid, a combined antibacterial medicine, demonstrated its clinical and microbiological efficacy in the treatment of patients with non-gonococcal urethritis of mixed etiology. PMID- 22066240 TI - [Erectile dysfunction: choice of the treatment method]. AB - The 15-year clinical experience with falloendoprosthetic operations (FEPO) in patients with erectile dysfunction is reviewed including algorithm of diagnostic examination, prostheses of different generations, indications and contraindications for falloendoprosthetic surgery. The results of 117 FEPO are outlined with special emphasis on 19 cases of postoperative complications. The conclusion is made that FEPO is most effective in erectile dysfunction by the presented criteria of the erectile dysfunction treatment efficacy. PMID- 22066241 TI - [Elective simultaneous operations in elderly and senile urological patients]. AB - Surgeons of Samara Regional Veterans' Hospital made elective-simultaneous operations in 229 presenile and senile patients. Surgery was performed in the urological department in 1995-2010. It is shown that over 12% patients of urological geriatric departments need elective situltaneous operations, of them 8.7% are mild, 78.6%--moderate and 12.7%--severe. The results of simultaneous operations in 133 patients and staged operations in 60 control patients (adenomectomy and Vinkelman) differed insignificantly (p > 0.05). Such achievement was realized due to advanced prophessional education of all medical personnel of the department, introduction of new techniques in examination and treatment: accurate definition of absolute and relative contraindications for simultaneous surgery, effective preoperative preparation, low-invasive operations, different variants of non-endotracheal anesthesia. In addition to a positive clinical effect, new technology of simultaneous operations reduces 2.3 fold economic costs vs staged surgery, improves significantly quality of life of the above patients. PMID- 22066242 TI - [Treatment of chlamydial infection in chronic prostatitis]. AB - Clinical efficacy of cycloferon (solution for injections) in combination with azitromycin was studied in males with newly diagnosed chronic prostatitis of chlamydial etiology and silent urogenital chlamydial infection. Administration of cycloferon in recommended regimen promotes clinical recovery and prevents recurrences. High clinical efficacy of cycloferon results from immunotropic activity of the drug which normalizes immune response and leads to elimination of the pathogen 3-6 months after the end of the treatment. PMID- 22066243 TI - [Methods of increasing the effectiveness of radical prostatectomy]. AB - In search of ways to improve the results of radical surgical treatment of patients with prostatic cancer (PC), we analysed the results of examination and treatment of 130 patients with local PC performed in 2000-2010 years. All the patients have undergone retropubic radical prostatectomy (RPE). Of them, 25.4% received neoadjuvant hormonal therapy. Follow-up median was 53 months (16-122 months). We also estimated direct and indirect costs of RPE. Erectile dysfunction after RPE was registered in 93.1% patients, urinary incontinence--in 20% patients, anastomosis stricture--in 22.6%. Five and 10 year recurrence-free survival was 80 and 72%, respectively. Total (direct and indirect) costs of one PC patient's surgical treatment (RPE) reached 140891,29 roubles. Our calculations show that certain measures taken in practical activity of the urologists can reduce direct costs by about 25%. Thus, our study demonstrates that it is possible to avoid unjustified expenses and achieve good outcomes in surgical treatment of PC. PMID- 22066244 TI - [Administration of vitaprost plus for prevention of infectious-inflammatory complications of transurethral prostatic resection in patients with prostatic adenoma]. AB - The study of efficacy and safety of the drug vitaprost plus (rectal suppositories) in its use for prevention of infectious-inflammatory complications after transurethral resection (TUR) of the prostate for adenoma included 55 male surgical patients with prostatic adenoma (PA). The patients were randomized into two groups matched by age, symptoms and clinical data. The control group consisted of 20 patients (group 1), the study group--of 35 patients (group 2). TUR of the prostate was made in both groups, but patients of group 2 were given additional prophylactic treatment--vitaprost plus, one suppository before going to bed 2 days before surgery and for 8 days after TUR, the course lasted for 10 days. Postoperative blood and urine samples showed inflammatory changes more often in group 1, free of infection bacterial tests were more often in group 2. Renal microcirculation in group 1 after TUR evidenced for functional depression on perfusion intensity and renal ischemia and congestion. These changes persisted on postoperative day 8, being a potential cause of renal inflammation and ascending pyelonephritis. Group 2 patients exhibited insignificant postoperative microcirculatory disorders in the kidneys and were not registered on postoperative day 8. Infectious-inflammatory complications in group 1 patients were registered much more frequently than in group 2 patients. Thus, vitaprost plus can be recommended for prophylaxis of infectious-inflammatory complications of TUR in PA patients. PMID- 22066245 TI - [The role of ultrasonography in diagnosis of cryptorchidism in children]. AB - Complex preoperative ultrasonic investigation of the inguinoscrotal area and abdominal cavity was made in 265 patients with cryptorchidism aged 1 to 14 years. The data of this investigation allowed development of an original technique of differential diagnosis of testicular retention and ectopy. Informative value of ultrasonic investigation in diagnosis of testicular ectopy and retention reached 100%. Examination of 44 children with unpalpable testes diagnosed abdominal cryptorchidism in 42 (65.6%) patients. In 10 (15.6%) patients testicular visualization failed. Testicular aplasia was diagnosed in 12 (18.8%) patients. Assessment of morphofunctional condition of the retained gonade showed that all the children had deficiency of testicular volume and abnormal intratesticular blood circulation. PMID- 22066246 TI - [Hormonal therapy of prostatic cancer: current status of the problem]. PMID- 22066247 TI - [Hormone replacement therapy in men: practical aspects]. PMID- 22066248 TI - [A giant recurrent urethro-vesico-vaginal fistula with a 44 year history with a complete prolapse of the urinary bladder]. PMID- 22066249 TI - [A giant prostatic adenoma without disturbance of patient's quality of life]. PMID- 22066250 TI - [Oral mucosa transplantation in extended urethral stricture]. PMID- 22066251 TI - [Surgical treatment of kidney calculi in the horse-shoe kidney]. PMID- 22066252 TI - [Prognostic value of ICP, CPP and regional blood flow monitoring in diffuse and focal traumatic cerebral lesions]. AB - Forty patients with severe traumatic brain injury (GCS score 8 and less) aged 16 54 years treated in our clinic were analyzed. Correlations between clinical symptoms, CT signs of diffuse and focal traumatic lesions, intracranial hemorrhage, indices of cerebral blood flow (CBF) according to perfusion CT study, intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were assessed. Main mechanism of injury in 27 of 40 (67.5%) patients was acceleration deceleration due to traffic accidents which usually leads to diffuse axonal injury (DAI) of different severity. In the other 13 (32.5%) cases injury was associated with coup-countercoup mechanism which caused focal contusions mostly. Not only GCS score but CT-signs of DAI severity, intracranial hemorrhage and minimal levels of CPP had significant prognostic value. Results of perfusion CT studies demonstrated that in 37 of 40 (92.5%) patients cerebral blood flow decreased (below 28.6 ml/100 g/min) in one or more arterial blood distribution areas. Increase of CBF was registered in 9 cases (over 69 ml/100 g/min), in 6 of them elevation of CBF in one arterial distribution area was associated with reduction in the other. Generally, mean CBF values were higher in the middle cerebral artery circulation than in the other. The lowest CBF levels (16.3 +/- 6 ml/100 g/min) were observed in cortical and subcortical hemorrhagic foci while these values were significantly higher in the same contralateral intact zones (36.0 +/- 10.0 ml/100 g/min; p < 0.01). In 3 patients with DAI the CBF in the midbrain varied from 12.5 to 30.1 ml/100 g/min with the lowest levels in hemorrhagic focus in cerebral peduncle. It corresponded to cystic-atrophic alterations found on subsequent follow-up MRI. Thus, reduction of CBF and episodes of low CPP were the leading pathophysiological phenomena of diffuse and focal brain damages. PMID- 22066253 TI - [Long-latency components (N100, N200 and P300) of acoustic evoked potentials in prediction of mental recovery in severe traumatic brain injury]. AB - The authors analyzed correlations of amplitude and latency levels of N100, N200 and P300 components of acoustic evoked potentials (AEP) registered during sonic stimulation and counting of target-oriented stimuli in 22 patients in vegetative state and mutism as an outcome of traumatic brain injury. Results were analyzed with association of electrophysiological findings with data of diffusion-tensor MRI. 55 healthy volunteers were included into control group. It is described that patients in vegetative state with formal recovery to the level of clear consciousness develop all three components of AEP in response to target-oriented tone. The instruction "to counts" leads to their better development. Patients with restoration to minimal level of consciousness produce all components during audition of sounds and only N100 and N200 in response to standard tone after instruction "to count". It is discovered that levels of amplitude have bigger correlation according to Spearman's criterion with outcome in comparison to latency. There changes are more prominent in N100 and N200 components rather in P300. In addition, after instruction "to count sounds" the registered changes between stages of vegetative state and mutism are significant for leads of left hemisphere, and during audition of sounds--for sagittal leads. The study showed correspondence of acquired changes with MRI data. Chronic unconscious state is associated with changes in corpus callosum (degeneration fibers) and corticospinal tracts in the brainstem. The data are discussed in light of hypothesis of the role of morphofunctional disconnections (brainstem-thalamus and interhemispheric) in impairment of attention and in genesis of different forms of posttraumatic unconscious state. PMID- 22066254 TI - [Syndrome of cerebral hyperperfusion after carotid endarterectomy]. AB - The aim of this study was to assess the role of different modalities in early diagnosis of cerebral hyperperfusion syndrome (CHPS) following carotid endarterectomy, as well as to develop effective treatment protocol for abovementioned complication. MATERIAL AND METHODS: Study group consisted of 61 patient who underwent uni- or bilateral carotid endarterectomy (CEA). Diagnostic modalities included transcranial Doppler study (TCD), cerebral oximetry, perfusion CT scanning and neuropsychological evaluation. STUDY RESULTS: We demonstrated that both bilateral carotid stenosis and stroke were independent predictive factors for CHPS at early postoperative period. "Classical" two-fold increase of cerebral blood flow in ipsilateral CMA was seen in 15% patients only. According to our data, predictive TCD-value was 1.48 increase of CBF. The most informative tool for early CHPS diagnosis was perfusion CT scans: preoperative mean transit time asymmetry in temporal areas (in the group of patients with unilateral carotid stenosis) correlated with CHPS development. Effective medical treatment for CHPS was achieved with Ca2+ channel antagonists use, that enabled us to prevent evolution of "mild" clinical appearance of CHPS into status epilepticus or intracerebral hemorrhage. CONCLUSION: Modern diagnostic modalities that assess brain perfusion can (with certain rate of accuracy) predict CHPS development even preoperatively. Early therapy of this complication with Ca2+ antagonists can usually control it. PMID- 22066255 TI - [The role of intraoperative flowmetry in surgery of cerebral aneurysms]. AB - Aim of the study was to assess the capabilities of intraoperative ultrasonic flowmetry in cerebral aneurysm surgery for prevention and immediate correction of cerebral ischemia. Ultrasonic flowmeter (Model HT313/323, "ransonic Systems Inc.", USA) was used during surgery in patients with complicated, large and giant aneurysms for evaluation of cerebral blood flow in main arteries (internal carotid, anterior and middle cerebral) and their branches (branches of M2-M3 and A2 segments). The series included 20 adult patients (13 male and 7 female) operated in Burdenko Moscow Neurosurgery Institute during 2008-2011 years. Mean age was 47.4 +/- 8.6 years. Giant aneurysms (> 2.5 cm) were present in 12 (60%) patients, large (1.5-2.5 cm)--in 5 (25%). Aneurysms of internal carotid artery were found in 8 cases. 1 female patient was operated on giant aneurysm of anterior cerebral--anterior communicating artery. In 4 (20%) cases significant alterations of blood flow were registered after clipping (> 25% according to initial), the changes were not visible. This allowed to correct the position of clips. In 2 surgeries ('low' paraclinoid aneurysms) the collateral flow was sufficient during temporary clipping, this allowed trapping of aneurysms with good neurological outcome. In 3 cases flowmeter was used to evaluate blood flow after extracranial-intracranial bypass. Ultrasonic flowmetry is a simple, reproducible and safe technique for intraoperative assessment of blood flow. Despite visual sufficiency of arteries flowmetry allows detection of surgically significant alterations of blood flow after clipping. PMID- 22066256 TI - [Clinical manifestation and surgical treatment of superior lumbar disc herniation]. AB - On the basis of analysis of presentation and surgical treatment of 103 patients with lumbar disc herniation the authors performed comparative assessment of symptoms and therapeutic techniques in patients with higher and lower lumbar disc disease. Short-term and long-term results were evaluated using visual analogue scale and Oswestry disability index (ODI). Statistically significant differences in dynamics of pain and ODI were not present. In spite of differences in clinical presentation, the results of surgical treatment in both groups were similar. They depended on severity of preoperative neurological deficit regardless of level of lesion. Specific features of surgical procedure in superior lumbar disk herniation are described. PMID- 22066257 TI - [Long-term results of surgical treatment for lumbar spine degenerative. Disease in patients above 60 of age]. AB - Aim of this study was to assess results of surgical treatment of patients with degenerative lumbar spine disease. MATERIAL AND METHODS: We analyzed 68 patients 65-82 years old. Clinical neurological examination, questionnaires, X-rays, multispiral CT scans were used for evaluation. RESULTS: After decompressive (group A) and decompressive-stabilizing surgery (group B) we observed significant decrease of low back pain intensity according to visual analogue scale (chi2 = 10.0; p = 0.024; p < 0.05) and leg pain intensity (chi2 = 24.4; p = 0.001; p < 0.05). However, Oswestry disability index (ODI) 4-6 years after decompressive stabilizing surgery remained substantially low in comparison with decompressive procedures. ODI after surgery also remained significantly lower in comparison with preoperative level in both groups (chi2 = 71.4; p = 0.001; p < 0.05), however, after decompressive-stabilizing procedures positive dynamics of ODI was more prominent. Complex assessment of treatment outcomes discovered significant difference in rates of good and poor results between two groups. Good postoperative results in group A reached 38.7% while in group B--67.6% (z = 2.2; p = 0.032; p < 0.05); poor results in groups A and B were 29.0% and 2.7%, respectively (z = 2.7, p = 0.007, p < 0.05). CONCLUSION: Decompressive stabilizing procedures are the most effective in treatment of degenerative lumbar spine disease. PMID- 22066258 TI - [Urgent neurosurgical operations in neurooncology]. AB - 26 patients with intracranial tumors on the stage of severe clinical decompensation were treated in S.P. Botkin Municipal Hospital from 2005 till 2010. The main group (18 cases) included patients who underwent urgent neurosurgical procedures due to decompensation. This group was evaluated prospectively. Control group (8 cases) consisted of patients who received only conservative treatment. Application of this therapeutic tactics allowed decrease of mortality from 100% after palliative conservative treatment to 11% (2 cases) after aggressive surgical management shortly after deterioration. Condition of patients was assessed using GCS. Outcomes were evaluated by GOS. Mean preoperative GCS score was 5.3 in the surgical group. In control group this value was 4. Mean postoperative GOS score was 3.9. In control group mortality reached 100%. Perioperative ICP monitoring demonstrated severe intracranial hypertension in all cases. Analysis showed that urgent decompressive procedure in decompensated patients with intracranial tumors is treatment of choice if antiedematous treatment is ineffective. If no positive dynamics in neurological symptoms is observed, neurosurgeon should immediately perform wide external and internal decompression with duraplasty. Decision about urgent operation is strictly individual and should be based on size and localization of the tumor, concominant diseases, duration of coma and stability of haemodynamics. PMID- 22066259 TI - [Surgical tactics in fractures of frontal bone involving frontal sinus]. AB - Review of literature dealing with fractures of frontal bone involving frontal sinus is presented. 3 cases of successful surgical treatment of different frontal sinus injuries are reported in the paper. The author demonstrates importance of selection of correct surgical tactics for primary reconstruction of frontal bone using craniofacial osteosynthesis. The key moment of surgical procedure is making a decision about preservation or elimination (obliteration or cranialization) of the frontal sinus which should be based on meticulous analysis of symptoms and CT data preoperatively and intraoperatively. Special attention should be paid to application of pericranial flap for closure of fractured posterior wall of the frontal sinus. Original technique of using a split pericranial pedicled flap for isolation of dura from sinus and stimulation of reparative osteogenesis is described. PMID- 22066260 TI - [Intraosseous cranioorbital hemangiomas]. AB - The authors describe 2 cases of primary intraosseous cavernous hemangioma (PICH). PICH are extremely rare tumors that represent less than 1% of all tumors of the bone. Only 20% of them involve skull. In both cases clinical findings were presented by proptosis, oculomotor disorders and chronic daily headaches. Surgery is the most recommended method of treatment. The best surgical management is gross total resection within intact tissue. In both cases tumor was removed completely. PMID- 22066261 TI - [Metastatic skull base tumors (biology, clinical presentation and evaluation)]. AB - Metastatic skull base tumors are rare and complicated lesions. They involve cranial nerves and craniobasal vascular structures causing multiform clinical presentation. Despite modern neurovisualization techniques, risk of preoperative diagnostic pitfall remains high. Final diagnosis and planning of further treatment are possible only after surgical removal of tumor with subsequent immunohistochemical verification. PMID- 22066262 TI - [Where intestinal epithelial stem cells are localized? About molecular markers]. AB - Using stem cells as an example the review considers a new history and methodology of search for stem cells (SC), found in tissues of adult Homo sapiens and Drosophila melanogaster organisms. These studies of SC resulted in several original hypotheses explaining their unusual features. Impressive progress recently achieved in this direction (2008-2010) is associated with employment of new methods of somatic recombination for long-term registration of various strains of differentiated cells, early and distant SC progeny. 1) Although anatomic localization of intestinal epithelium cells lacking marked morphological and biochemical differentiation markers (the lower third of intestinal and colon crypts) is known for about 40 years results of their experimental identification, isolation and detection of their functional characteristics still represent the subject for discussions. Particularly, it remains unclear, which SC are involved in crypt regeneration: the same as those involved into homeostatic renewal or their various subpopulations or early SC progenies acquired stem features by reprogramming? 2) In addition, most detected biochemical markers of potential SC are common for SC from other tissues of embryonic and mature organisms so it is possible to apply method developed for intestinal epithelium for their isolation. 3) Data on induction of intestinal epithelium polyps and neoplasias by mutations in genes encoding SC markers and identification of biochemical characteristics of potential SC in these tumors support the hypothesis of stem tumor cell origination from normal SC or their earliest progeny. In general, facts considered in this review may be useful for both development of optimal methods for the use of SC in cell therapy (as the source of humoral factors), regenerative medicine (as the source of differentiated cells for restoration of injured tissue), and also for targeted search of antitumor drugs (SC as the target) and preparations modifying genetic and epigenetic reactions of SC to genotoxic and stress treatments. PMID- 22066263 TI - [Poly(3-hydroxybutyrate) and biopolymer systems on the basis of this polyester]. AB - Biodegradable biopolymers attract much attention in biology and medicine due to its wide application. The present review is designed to be a comprehensive source for research of biodegradable and biocompatible bacterial polymer, poly(3 hydroxybutyrate). This paper focuses on basic properties of biopolymer: biodegradability and biocompatibility, as well as on biopolymer systems: various materials, devices and compositions on the basis of biopolymer. Application of biopolymer systems based on poly(3-hydroxybutyrate) in medicine as surgical implants, in bioengineering as scaffold for cell cultures, and in pharmacy as drug dosage forms and drug systems is observed in the present review. PMID- 22066264 TI - [Study of Dj-1 protein in tissue specimens, cultured cells and serum of prostate cancer patients]. AB - Two isoforms of Dj-1 protein were identified using a proteomic study in tissue specimens from two groups of patients with confirmed benign prostate hyperplasia (BPH) and prostate cancer (PCa). Dj-1 was also found in the cell lines PC-3, DU 145, LNCaP, BPH-1, and the lowest level of Dj-1 was found in BPH-1. Immunochemical study (ELISA) of serum levels of Dj-1, Bcl-2, IGF-1 and IGFBP-3 proteins revealed statistically significant distinctions between two groups of patients (p=0,004, Mann-Whitney test) only for Dj-1. Taken together, these data suggest that Dj-1 protein is a perspective biomarker candidate for PCa. PMID- 22066265 TI - [Screening of potential substrates or inhibitors of cytochrome P450 17A1 (CYP17A1) by electrochemical methods]. AB - The electrochemical reduction of the recombinant form of human cytochrome P450 17A1 (CYP17A1) was investigated. Hemeprotein was immobilized on electrode modified with biocompatable nanocomposite material based on the membrane-like synthetic surfactant didodecyldimethylammonium bromide (DDAB) and gold nanoparticles. Analytical characteristics of DDAB/Au/CYP17A1 electrodes were investigated with cyclic voltammetry, square wave voltammetry, and differential pulse voltammetry. Analysis of electrochemical behaviour of cytochrome P450 17A1 was conducted in the presence of substrate pregnenolone (1), inhibitor ketoconazole (2), and in the presence of synthetic derivatives of pregnenolone: acetylpregnenolone (3), cyclopregnenolone (4), and tetrabrompregnenolone (5). Ketoconazole, azole inhibitor of cytochromes P450, blocked catalytic current in the presence of substrate pregnenolone (1). Compounds 3-5 did not demonstrate substrate properties towards electrode/CYP17A1 system. Compound 3 did not block catalytic activity towards pregnenolone, but compounds 4 and 5 inhibited such activity. Electrochemical reduction of CYP17A1 may serve as an adequate substitution of the reconstituted system which requires additional redox partners - for the exhibition of catalytic activity of hemoproteins of the cytochrome P450 superfamily. PMID- 22066266 TI - [Renin-angiotensin system gene expression in the kidney and in the heart in hypertensive ISIAH rats]. AB - The content of mRNA of renin-angiotensin system (RAS) genes in the kidney and heart of hypertensive ISIAH and normotensive WAG rats was measured by the real time PCR. Statistically significant decrease of RAS gene mRNA was registered in the kidney of ISIAH rats, including Ren (by 45%), Ace (43%), AT1A (34%), COX-2 (50%). In the myocardium AT1A mRNA expression decreased by 28% while Ace mRNA expression increased by 80%. These results demonstrate the reduction of renal RAS basal activity in the hypertensive ISIAH rats, and this allows us to consider the ISIAH rat, as a low-renin hypertensive strain. In support of this viewpoint, in the ISIAH rats, a two-fold increase in the connective tissue sodium concentration as well as statistically significant plasma sodium increase (from 136 +/- 0,25 micromol/l in WAG to 139 +/- 0,3 micromol/l in the ISIAH rats) were found. Our conclusion backed by a tendency of the ISIAH plasma aldosterone level decrease giving in sum a classical picture of a low-renin hypertensive state in the ISIAH rats. It was suggested that the formation of low-renin arterial hypertension in the ISIAH rats may depend on changes in kidney ion channels function. In addition, renal NO system alterations could be also involved in the pathogenesis of arterial hypertension in the ISIAH rats. PMID- 22066267 TI - [Regularities of endogenous lipid metabolites formation in phorbol 12-miristate 13-acetate-stimulated peripheral blood lymphocytes at leukemia]. AB - Regularities of biologically active lipid metabolites formation in dynamics (5, 10, 30, 60 s) by phorbol 12-miristate 13-acetate stimulation in [14C]palmitic acid have been investigated in normal and leukemia peripheral blood lymphocytes prelabeled with [14C]palmitate. In normal cells there was two-phase formation of 1,2-diacylglycerol (5, 30 s), lysophosphatidylcholine (10, 60 s), as well as free palmitic acid at 10 s of stimulation. Under the identical experimental conditions there was inhibition of investigated lipid release processes at early (5 and 10 s) stages of stimulation of leukemic lymphocytes. At later (30, 60 s) terms of these lymphocytes the activation, basically, similar to norm changes in the formation of palmitic acid-containing metabolites except free palmitic acid (the level of which raised only at 60 second of the post-stimulation) was found. Various protein kinases C are involved in the regulation of investigated lipid levels at certain stages of signal transduction both in norm, and in blast cells. Short-term (5, 10 s) activations of healthy donors lymphocytes are coupled to functioning of Ca2+-independent isoforms of protein kinase C. The inhibition of this protein kinase C in leukemic cells leads to normalization of the investigated lipid release. The data obtained suggests disorders of early membrane-bound reactions in agonist - and a protein kinase C-mediated processes of formation palmitic acid-containing lipid metabolites in the leukemic cells in comparison with the norm. PMID- 22066268 TI - [Studies of mutagenic activity of positively charged alkyl glycerolipids in Ames test]. AB - Mutagenic activity of non-phosphorous cationic alkyl glycerolipid rac-N-{4-[(2 Methoxy-3-octadecyloxy)propyl]oxycarbonylbutyl}-N,N-dimethyl-N-(2-hydroxyethyl) ammonium iodide was evaluated. According performed Ames assay results indicated on non-mutagenic properties tested compound. Resulting data open the possibility to carry out biological study in vivo for class of ether cationic glycerolipids and further applications as a potential agent of anticancer therapy. PMID- 22066269 TI - [All signs of metabolic syndrome in the hypertensive ISIAH rats are associated with increased activity of transcription factors PPAR, LXR, PXR, and CAR in the liver]. AB - It is known that the metabolic syndrome (MS), which includes hypertension, dislipidemia, glucose intolerance, and obesity leads to cardiovascular diseases. The MS risk is growing catastrophically. Molecular mechanisms allowing to understand the reason of integrated dysfunctions, taking place at MS cases, have remained almost unstudied. The chronical stress plays a crucial role in MS development; therefore in the present work a hypertensive rat strain with Inherited Stress-Induced Arterial Hypertension (ISIAH) was used as a model. It was shown that ISIAH rat strain as compared with the control WAG rat strain is characterized by increased content of triglyceride, VLDL and LDL cholesterols, a decreased content of HDL cholesterol, a high level of apolipoprotein B-100, and decreased level of apolipoprotein A-I. The ISIAH rats body weight was higher as compared with WAG rats; ISIAH rats blood glucose content was higher too. Thus, strain hypertension for ISIAH rat is accompanied by dislipidemia, increased glucose content, and increased body weight, representing a whole set of MS signs. Since at MS cases the systemic abnormalities in lipid and carbohydrate metabolism take place, the functional activity of transcription factors (TFs) participating in integral regulation of lipid and carbohydrate metabolism genes in liver was measured. PPAR, LXR, PXR, CAR DNA-binding activity was increased in ISIAH rats, suggesting involvement of these TFs in MS development. Integrated investigation of PPAR, LXR, PXR, CAR regulatory mechanisms, signal transduction and transcriptional targets will provide insights into the pathogenesis of MS and offer valuable information for designing of drugs for MS treatment. PMID- 22066270 TI - [Effect of N-stearoylethanolamine on free amino acid levels in rat plasma and liver with burn]. AB - The effect of the endocannabinoid congener N-stearoylethanolamine (NSE) on the content of plasma and liver free amino acids in burned rats was studied. The animals after the thermal burn of the skin received per os during 7 days the water suspension of NSE in the doze 10 mg/kg of body weight. In the other group of rats the suspension was applied on the wound (the concentration of NSE was 10 mg/ml). In experimental animals the total amount of free amino acids in plasma decreased after burn while the total amount of free amino acids in liver significantly increased. In burn animals the ratio of plasma and liver Phe/Tyr and Gly/Val was found to be augmented while the Fischer ratio (Ile+Leu+Val/Phe+Tyr) diminished compared with intact rats. It was shown for the first time that NSE caused normalization of the concentration of some free amino acids and of Phe/Tyr, Gly/Val ratios, and the Fischer ratio in blood plasma and liver of rats with the burn injury. Altogether, these data demonstrate that NSE possesses adaptogenic properties, and is involved in the organism response to a burn. These findings suggest possibility of NSE usage for burn treatment. PMID- 22066271 TI - [Study of cytokines content and gangliosides metabolism at experimental brain edema]. AB - The content of cytokines, and gangliosides metabolism, and the quantity of lipid peroxidation products were studied at experimental brain edema. Data obtained show increase the level of proinflammatory cytokins and decrease the level of antiinflammatory cytokines during development of brain edema. Along with this we reveal the accumulation of lipid peroxidation products (diene conjugates, hydroperoxides, and malonic dialdehyde). Each fraction of gangliosides decreased, but the product of their hydrolytic dissociation sphingosine increased at experimental brain edema. PMID- 22066272 TI - [Neopterin as a rarameter, reflecting the inflammatory phase of a dermal wound process]. AB - Effectiveness of the influence of a natural cytokine complex "Superlymph" on a wound process was evaluated in albino rats. The preparation was used right after surgical treatment and then during 5 days. Interrelationship between morphological and immunobiochemical factors on local and organismic levels was studied. During uncomplicated wound process no statistically significant difference in concentration of blood serum neopterin was found. The main changes occured locally. There was correlation between morphological and immunobiochemical factors. PMID- 22066273 TI - [Mass-spectrometric investigation of degradation of the inhalation anesthetic sevoflurane in flow anesthesia]. AB - The highest concentration of the Sevoflurane degradation product in the gas mixture was 65 ppm. Biochemical analysis did not reveal any nephro- and hepatotoxic effect. PMID- 22066274 TI - Prevalence of and predictors of substance use among adolescents in rural villages of Moshi district, Tanzania. AB - PURPOSE: To determine the prevalence of substance use among primary school pupils and out-of-school adolescents in Moshi rural district, northern Tanzania. METHODS: A school-based cross-sectional study focusing on primary school adolescents in standards 6 and 7 in Kahe rural community. We also conducted a population-based cross-sectional study among out-of-school adolescents in the same rural villages. A self-administered questionnaire was used to collect data from the school-based survey while for the out-of-school survey the questionnaire was administered in the households using trained interviewers. RESULTS: A total of 545 in-school and 668 out-of-school adolescents participated in the study. Of the 545 school adolescents, 45.4% were males and 56.6% females while for the out of-school adolescents, 68.1% were males and 31.9% females. Of the school adolescents, more males than females reported being alcohol drinkers (16.7% versus 9.2%; odds ratio (OR) = 1.9, 95% CI, 1.17 - 3.29). The prevalence proportions of cigarette smoking were 26.2% for men and 15.5% for women while prevalence proportions of marijuana smoking were 4.1% for men and 3.0% for women. As for the out-of-school adolescents, the prevalence proportions of alcohol use were 26.2% for men and 15.5% for women. The prevalence proportions of cigarette smoking were 14.3% for men and 1.9% for women while the prevalence proportions of marijuana smoking were 1.5% for men and 1.4% for women. CONCLUSIONS: Substance use among adolescents is very high suggesting the need for interventions in this rural population of Tanzania. PMID- 22066275 TI - Epidemiology of non-penetrative sex among university students in the context of HIV/AIDS prevention in Northwestern Ethiopia. AB - OBJECTIVES: This study was conducted to explore the knowledge, attitude and practices related to non-penetrative sexual behavior in the context of HIV/AIDS prevention among Bahir Dar University students in Northwestern Ethiopia. METHODS: We conducted a cross-sectional study among a representative sample of 624 regular students attending their education in academic year 2007 in Bahir Dar University in Ethiopia selected by stratified sampling technique. Association between practices and the explanatory variables was assessed in bivariate analysis using Chi-square tests and the associations were further expanded using multivariate logistic regression analysis. RESULTS: The overall knowledge assessments of the respondents showed that 65.2% of the respondents were having reasonable and good knowledge. Around 46.7% were currently practicing one or more of the non penetrative sexual practices. Among those who were practicing one or more of the non penetrative sexual behaviors (n = 286) were for the reasons as make sexual pleasure (56.8%), prevent HIV and STI (49.8%), keeping virginity (17.1%) and prevention of pregnancy (16.7%)respectively. Around 60.7% had unfavorable attitude towards non penetrative sexual behavior. Having good knowledge, being male gender, and having favorable attitudes towards NPS were associated with non penetrative sexual practice. CONCLUSIONS: Most of the students have relatively good knowledge and a considerable proportion of them were already engaged in one of the NPS practices withstanding the unfavorable attitude they have towards NPS. This remained that it is advisable to further consider NPS as one option and additional menu for avoiding unwanted penetrative sex in order to maximize young people's options to prevent HIV/AIDS and STIs along with broader IEC/BCC interventions. PMID- 22066276 TI - Socio-demographic correlates of sexual behaviours: a cross sectional survey of adolescents in Imo State secondary schools. AB - The study was designed to determine the socio-demographic correlates of sexual behaviours of the adolescents in Imo State secondary schools. Three objectives and three hypotheses were formulated to guide the study. A cross sectional survey design was used and sample size was 3360 (2.2%) adolescents. A structured, validated and reliable questionnaire (r = 0.79) and focus group discussion were used as the instruments for data collection. Data analysis was done using mean and ANOVA statistics. The result generally, showed that the average sexual behaviours of the adolescents were below the decision mean of 2.50 and as such the adolescents were said to be sexually inactive. In Imo State secondary schools, various family sizes did not significantly influence the sexual behaviours of the adolescents (F-cal. 2.39, F-tab. 3.00 & P > 0.05), family structure significantly influenced their sexual behaviours (F-cal. 17.78, F-tab. 3.00 & P < 0.05) and different financial strengths influenced the adolescents sexual behaviours significantly (F-cal. 22.88, F-tab. 2.37 & P < 0.05. Of great worry is that unrestricted/uncontrolled adolescents sexual behaviours may expose them to sexually transmitted infections/HIV/AIDS, unwanted pregnancies, illegal abortion and dropping out of school. Thus comprehensive sex education was recommended. PMID- 22066277 TI - Stress, motivation and professional satisfaction among health care workers in HIV/AIDS care and treatment centers in urban Tanzania: a cross-sectional study. AB - BACKGROUND: Shortages of health care workers (HCWs) represents a serious challenge to ensuring effective HIV care in resource-limited settings (RLS). Stress, motivation, and job satisfaction have been linked with HCW retention and are important in addressing HCW shortages. In this cross-sectional study HCW stress, motivation and perceived ability to meet patient needs were assessed in PEPFAR-supported urban HIV care and treatment clinics (CTCs) in Tanzania. METHODS: A self-administered questionnaire measuring motivation, stress, and perceived ability to and meet patient needs was given to HCWs at 16 CTCs. Scales measuring HCW satisfaction, motivation, and stress were developed using principle components analysis. Hierarchical linear models were used to explore the association of HCW and site characteristics with reported satisfaction, stress, motivation, and ability to meet patients' needs. RESULTS: Seventy-three percent (279) of HCWs completed the questionnaire. Most (73%) HCWs reported minimal/no work-related stress, with 48% reporting good/excellent motivation, but 41% also reporting feeling emotionally drained. Almost all (98%) reported feeling able to help their patients, with 68% reporting work as rewarding. Most reported receipt of training and supervision, with good availability of resources. In the multivariate model, direct clinical providers reported lower motivation than management (p < 0.05) and HCWs at medium-sized sites reported higher motivation than HCWs at larger sites (p < 0.05). HCWs at small and medium sites were more likely to feel able to help patients than those from larger sites (p < 0.05 and p < 0.001 respectively). CONCLUSION: Despite significant patient loads, HCWs in these PEPFAR-supported CTCs reported high levels of motivation, job satisfaction, ability to meet patients' needs, low levels of stress but significant emotional toll. Understanding the relationship between support systems such as strong supervision and training and these outcomes is critical in designing interventions to improve motivation, reduce stress and increase retention of HCWs. PMID- 22066278 TI - Schistosomiasis in Cameroon: an assessment of community knowledge pattern. AB - OBJECTIVE: Schistosomiasis is one of the most widespread of all human parasitic diseases and is a serious health problem in Cameroon despite tremendous efforts by health authorities. The purpose of this study was to determine community knowledge of the infection in order to evaluate control programmes put in place. METHODS: A random sampling method was used to administer questionnaires to 3200 individuals in 80 communities throughout the ten regions of the country. RESULTS: Globally the percentage of persons with good knowledge of schistosomiasis was low (28.8%). Of the 2586 who responded 1311 (50.7%) were females and 1275 (49.3%) were males. There was a statistically significant difference in the community knowledge pattern by gender (chi2 = 157.28, P < 0.05), and persons with good knowledge were more frequent among males than females (61.8% vs. 38.2% P < 0.05). The percentage of people who had good knowledge about the disease was highest in the Far North region (35.4), followed by the North (33.8) and the Southwest (31.1) regions. There was a statistically significant difference in community knowledge pattern of Schistosomiasis by region and gender (chi2 = 1265.648 P < 0.001). Also, there was a statistically significant difference in community knowledge pattern of by setting (chi2 = 38.538 P = 0.001) and the percentage of people who had a good knowledge of the disease was higher in rural areas than in urban areas (72.5% vs. 3.1% P < 0.05). CONCLUSION: was a low community knowledge pattern of schistosomiasis, mostly among the female population and among people living in urban areas. We advocated that health education should be adopted as one of the control strategies by the PMID- 22066279 TI - Herpes simplex virus type-2 and human immunodeficiency virus infections in a rural population in Kilimanjaro Tanzania. AB - OBJECTIVES: To estimate the seroprevalence of Herpes Simplex Type 2 (HSV-2) and its association with Human Immunodeficiency Virus type 1 (HIV-1) infections in rural Kilimanjaro Tanzania. METHODS: A cross-sectional survey was conducted in Oria village from March to June 2005 involving all individuals aged 15-44 years with permanent address in the village. Following an informed written consent, participants gave blood for HIV-1 testing and further interviewed regarding their risk behaviours. All HIV cases and randomly selected controls were tested for HSV 2 antibodies. RESULTS: The weighted HSV-2 seroprevalence estimate in the whole population was 33.2%. The HSV-2 seroprevalence was 87.5% and 29.5% among HIV-1 seropositive cases and seronegative controls respectively (Odds ratio (OR) 2.9; 95% Confidence interval: 1.9-4.3). After adjusting for sexual risk behaviors, the association between HSV-2 and HIV-1 infections remained strong (adjusted OR 14.1; CI: 5.0-28.3). Multiple sexual partners, transactional sex and unprotected casual sex were independently associated with HIV-1 infection. CONCLUSIONS: These results demonstrate that HSV-2 is highly prevalent in rural communities in Tanzania and strongly associated with HIV-1 infection. Sexual risk behaviours may play a major role in the transmission of both HSV-2 and HIV-1 infection. Due to lack of HSV-2 suppressive antiretroviral therapy in this and similar communities, prevention through promotion of behavioural change might be the most important strategy to mitigate HSV-2 and HIV-1 transmission. PMID- 22066280 TI - Primary motives for demand of ivermectin drug in mass distribution programmes to control onchocerciasis. AB - BACKGROUND: This report of a survey study presents findings from a sample of 594 persons out of a total of 35,763 treated individuals who voluntarily demanded Ivermectin treatment during a community-based Ivermectin distribution exercise. The distribution, which took place in 2008, was the seventh in the planned ten or more years of mass distribution of the microfilaricide to control onchocerciasis in endemic communities of Ezinihitte in the Imo River Basin of Nigeria. METHODS: The subjects were selected by quota sampling procedure on the basis of community and gender, and were asked to rank-order six plausible reasons for seeking treatment in terms of their order of importance in motivating them to demand Ivermectin. RESULTS: "To gain treatment and prevention of Skin Problems" and "Desire to be De-wormed" ranked first and second respectively. "To gain promotion of general wellbeing" and "To improve state of vision and prevent of blindness" ranked third and fourth respectively. In the fifth and sixth rank-ordered positions were "To prevent hanging groin" and "to prevent/relieve enlargement of the scrotum or clitoris" in that order. A test of hypothesis to determine if there was significant agreement among treated persons on the rank order of importance of their reasons for demanding Ivermectin gave a Kendall's Coefficient of Concordance of, W = 0.62, p < 0.01. CONCLUSION: The findings are interpreted within the framework of the major postulations of the health belief model with consideration to perceptions of severity of the conditions and belief that submitting to treatment will abate the perceived risk of the conditions. The role of endemicity of specific manifestations of onchocerciasis in lay assessment of risk of this disease is also discussed. PMID- 22066281 TI - Birthing support and breastfeeding initiation in Somaliland: experiences at the Edna Adan Maternity Hospital in Hargeisa, Somaliland. AB - BACKGROUND: Research has identified a relationship between birthing practices and breastfeeding initiation Continuous support during labor and delivery is a key component to increasing breastfeeding initiation. OBJECTIVE: The purpose of this project was to assess the impact of labor support on breastfeeding initiation in a setting in which women receive traditional birthing support from female family members. METHODS: Research was conducted at the Edna Adan Maternity Hospital in Hargeisa, Somaliland using the grounded theory method of qualitative research. Semi-structured interviews, direct observations and participant observations were conducted. A purposeful, non-statistical sample was chosen: ten women, five family members, six health care providers and five birth observations were included. The CDC EZ-Text, a software program developed by the Center for Disease Control and Prevention for use in qualitative research, was used in managing and analyzing the data. Data analysis and interpretation was conducted using micro analysis, open, axial and selective coding procedures. RESULTS: The results indicated that due to cultural influences, contradictory beliefs and practices, lack of critical thinking and lack of long term planning, traditional birthing support was not always indicative of immediate breastfeeding initiation. CONCLUSIONS: The presence of a labor companion is a low-cost, preventative intervention that is consistent with the cultural practices of Somaliland. Breastfeeding education and support should, therefore, include a tertiary approach which includes pregnant and birthing women, labor support persons or family members and health care providers. PMID- 22066282 TI - Bacteriological quality of water and water borne diseases in Bangalore: a longitudinal study. AB - In developing countries diarrhea diseases take a big toll which can be prevented by adequate supply of safe drinking water. Thus a longitudinal study was taken up to determine the morbidity due to water borne diseases and bacteriological quality of water. 150 houses in two different areas, one supplied by bore well and other by tap water was selected by modified cluster sampling. Weekly morbidity details collected. Monthly water samples were assessed for bacteriological quality from main supply, household storage and morbidity reported houses. The difference in proportion of potable and non potable water at storage points was statistically significant. The overall incidence rate of target diseases was 3.58%,majority were diaarrhoel diseases with increased incidence in children less than five years. PMID- 22066283 TI - Demographic and health indicators as predictors of life expectancy in African countries: implications for population education and health promotion in Nigeria. AB - This study was meant to analyse the relationship between vital statistics and life expectancy as measure of population control and welfare of citizenry in African countries and lessons Nigeria could draw from it. Thirty-one African countries were sampled for the study using data sourced from UNICEF-vital statistics (2010). Two hypotheses were tested and it was found that although there was negative correlation between demographic variables and life expectancy, demographic variables were not predictor of life expectancy. Although, environment/preventive health variables were collectively predictors of life expectancy, individually they were not. Nigeria should draw lessons on reducing under 5 and infant mortality, continuous improvement on water, sanitation, expanded programme on immunization and increase use of treated mosquito net to improve life expectancy. PMID- 22066284 TI - Utilization of health care services by pregnant mothers during delivery: a community based study in Nigeria. AB - OBJECTIVE: Poor utilization of health facilities during delivery by pregnant mothers is still a major cause of maternal and childhood morbidity and mortality in Nigeria. The aim of this study was to determine the level of utilization of health care services by pregnant women during delivery in Gokana Local Government Area of River State, Nigeria. MATERIALS AND METHODS: This was a cross-sectional, questionnaire; based study involving 112 mothers aged 15 years to 49 years from Gokana Local Government Area of Rivers State, Nigeria. The local Government Area has 12 health centres and 6 health centres were selected by multistage sampling. 112 were then selected by simple random sampling. RESULTS: Of the 112 mothers interviewed 91 (81.3%) were married, 13 (11.6%) were single, 5 (4.5%) were widows, 2 (1.8%) divorced and 1 (0.9%) separated. Ninety seven (86.6%) of these mothers (n = 112) had formal education while 15 (13.4%) had no formal education. Most 42 (37.5%) of the mothers were between 25-29 years. Sixty four (57.1%) of the 112 mothers in their recent delivery used a health facility while 48 (42.9%) did not. Factors responsible for non utilization of health facility for delivery include: Long distance to health facility 33 (68.7%), onset of labour at night 40 (83.3%), unavailability of means of transportation 37 (77.1%), Lack of money for transportation 26 (54.2%), unsatisfactory services at health facility 26 (54.2%), unfriendly attitude of staff of the health facility 34 (70.8%), unavailability of staff at health facility 32 (64.0%), lack of urgency at health facility 36 (75.0%), previous uneventful delivery at the health facility 32 (66.7%). CONCLUSION: Utilization of health care services during delivery in Nigeria is still poor. Concerted efforts should be made both at community and Government levels to improve utilization of health facility during delivery. This will go a long way in reducing maternal and child mortality. PMID- 22066285 TI - Availability and affordability of anticancer medicines at the Ocean Road Cancer Institute in Dar es Salaam, Tanzania. AB - BACKGROUND: To ensure effective control of cancer, patients undergoing chemotherapy should get continuous supply of anticancer medicines. In Tanzania and other East African countries little is documented regarding the availability and affordability of anticancer medicines at the patient level. The number of anticancer medicines prescribed to the cancer patients and its cost implication is also not known. OBJECTIVE: To determine the availability of anticancer medicines to patients attending chemotherapy clinic at Ocean Road Cancer Institute (ORCI) in Dar es salaam, Tanzania. Also to find out the prices of anticancer medicines in private pharmacies and affordability by cancer patients treated at ORCI. METHODOLOGY: A cross-sectional study was carried out between February and May 2010 in patients receiving cancer chemotherapy at ORCI. A total of 384 adult cancer patients registered for chemotherapy were included in the study. Patients, health care providers at the chemotherapy department and dispensing personnel in the private pharmacies were interviewed regarding availability, accessibility and affordability of anticancer medicines. RESULTS: The mean anticancer medicines prescribed per patient was 2.01, with the mean cost for anticancer drugs reported by patients to be 106,300 shillings. The availability of medicines at the ORCI for the management of cancer patients was about 50% of all surveyed medicines. As a result more than 70% of patients did not get the prescribed anticancer medicines at the hospital. In the private pharmacies, the unit cost for anticancer medicines was very high, ranging from 2,500 to 744,000 shillings, which is equivalent to 1-7 months income of the patient. CONCLUSION: Availability of anticancer medicines at ORCI in Dar es Salaam is not adequate. As a result, some patients are required to buy anticancer medicines from private pharmacies. In these private pharmacies anticancer medicines are too costly and most patients are not covered by health insurance to purchase their medicines. Efforts should be made to increase budgetary allocation to ensure adequate and uninterrupted supply of anticancer medicines to cancer patients at ORCI. PMID- 22066286 TI - Seroprevalence of ovine brucellosis in south Wollo, north eastern Ethiopia. AB - A cross-sectional study was conducted in south Wollo zone, north east Ethiopia between October, 2008 and March, 2009 aimed at determining the sero-prevalence and to identify potential risk factors of ovine brucellosis. A total of 800 sheep were sampled from two districts, Kalu and Harbu. All sheep above six months of age with no history of previous vaccination against brucellosis were selected. Rose Bengal Plate Test (RBPT) was utilized as a screening test for Brucella agglutinins while Complement Fixation Test (CFT) (Addlestone, United Kingdom) was used to confirm the reactors by RBPT. Over all seroprevalence of 1.5% (12 of 800) ovine brucellosis was observed. Seroprevalence was higher in female sheep compared to male sheep. Seroprevalence was calculated between sexually immature and sexually mature sheep, between animals kept under extensive and semi intensive management system, and between animals of the two districts. Higher levels of sero-prevalence was observed in sexually mature sheep, in animals kept under extensive management system, and in sheep of Kalu with level of 1.54%, 1.6% and 1.58%, respectively. However, there was no statistically significant difference between the sero-prevalences of brucellosis in the different study groups of sheep. In conclusion, even though the prevalence of brucellosis observed in this study is low, it can be potential hazard for public health in the study area; therefore, the public especially small ruminant producers should be informed about the risk of ovine brucellosis. PMID- 22066287 TI - AIDS awareness among women and its influence on attitude toward people living with HIV/AIDS in Burundi. AB - OBJECTIVE: To evaluate women's knowledge on HIV and their attitude toward AIDS infected people. METHODS: Structured and oriented questionnaire on AIDS knowledge, behavior and attitude toward people with HIV/AIDS, sources of information was used in assessing women's level of AIDS awareness. 2042 women participated in this study. RESULTS: Living in urban area was associated with taking care without worry (OR: 0.59; CI: 0.37-0.95; P = 0.02) and eating on same plate (OR: 0.44; CI: 0.33-0.74; P = 0.07). Catholic religion (OR: 1.79; CI: 1.09 2.24; P = 0.03) and protestant (OR: 2.09; CI: 1.19-3.70; P = 0.06) were associated with taking care without worry. Good knowledge was associated with taking care without worry (OR: 1.08; CI: 1.09-2.94; P = 0.04) and with sharing same work office (OR: 0.87; CI: 2.49-3.61; P = 0.03). Sources of information were ranked from health care workers (97.5%), mass media (91.2%) and clerical leader (87.9%). CONCLUSION: This research revered discrepancies on HIV knowledge between urban and rural women. Misunderstanding on HIV/AIDS remains in Burundi women even having high level of awareness. Communication between parents/women and friend/friend women was less used in HIV sensitization. Knowledge alone cannot counter bad behavior and attitudes toward people with HIV. PMID- 22066288 TI - Prevalence of osteopenia among sedentary young women. AB - The purpose of this study was evaluating prevalence of osteopenia in young women.40 young untrained women between the age of 20-25 years (obese n = 20, BMI > 30 and thin n = 20, BMI < 20) volunteered to participate in this study. Bone mass density (BMD), percentage body fat and lean mass (g/cm2) were measured with the dual X-ray absorptiometry scans (DEXA). Student's t-test was used for determining the amount of bone normalizing among subjects. The study finding showed that 20% of obese and 65% of thin women had osteopenia and thin groups 3.2% more than obese groups were at risk of bone loss. These findings will help educate the medical community and the public about the importance of prevention- targeting young women who are at risk while they still have time to change their habits and improve their bone health. PMID- 22066289 TI - Sexual behavior and condom use in female students in Dar-es-Salaam, Tanzania: differences by steady and casual partners. AB - OBJECTIVE: In Tanzania female youth are increasingly becoming at greater risk of sexually transmitted HIV infection, whereby more than 80% cases occur through un protected sex. The objective of this study was to examine related-factors which influence female students to have risky sexual contacts with casual partners including condom use and sex with sugar daddies. METHODS: A cross section study involving face-to-face interview was conducted regarding sexual behavior among 219 sexually-debuted female students aged between 18 and 24 years who were attending high schools and colleges in Dar-es-salaam, Tanzania. RESULTS: Eighty three percent had at least one boyfriend in the past 12 months, 57% had engaged in sex with a "sugar daddy", and 24% had engaged in sex with a casual partner other than a sugar daddy. Sixty-nine percent had ever used a condom, and 66% had used a condom during their most recent sexual encounter. Thirty-two percent reported always using a condom during sex with their boyfriends, whereas only 2% always used a condom with a sugar daddy. Decision-making about condom use during sex with boyfriends was made by couples together (48%) or by the girls alone (34%), whereas the decision during sex with a sugar daddy was predominantly made by the male partner (79%). Data were analyzed using Statistical Package for Social Sciences (SPSS) version 9.5 for frequencies, cross-tabulations and chi squired test and statistical significance set at p<0.05. CONCLUSION: The study highlighted risk factors for female students towards HIV infection. Receiving money and/or presents were the major motivations for having sex irrelevant with types of sex partners. Although most female's students disagreed in principle to have sex in exchange for money or presents, sex with sugar daddies was common among female students and was a major risk factor for HIV infection. Based on the findings, recommendations for improvement in prevention programs among female youth within Tanzanian context are discussed. PMID- 22066290 TI - Reported human traffickers' profiles: a key step in the prevention of trafficking in persons through HIV and AIDS interventions in Tanzania. AB - OBJECTIVE: a gap in comprehensive knowledge of trafficking in persons and the traffickers exists globally and in Tanzania in particular. Consequently, information on the profiles of human traffickers in the country is tremendously scanty. METHODS: we conducted a baseline study in eight administrative regions of Tanzania Mainland using both qualitative and quantitative methods to generate data in to inform anti-human trafficking health interventions and programs to be implemented in the country. Study participants included the national, regional and district Community Development Officers, District Medical Officers, local government leaders, managers or representatives of non-governmental organizations involved in anti-trafficking in persons activities, members of the community and victims. RESULTS: different individuals or groups, knowingly or ignorantly, contribute to trafficking in persons and their roles differ at the places of origin, transit and destinations. Traffickers are males or females with varied age, marital status, relationships with victims, socio-economic status, experience and occupations. CONCLUSIONS: active traffickers at many stages of this crime rarely come into contact with the law enforcement system; fled or rescued victims may not be willing or unable to testify against their traffickers and coercing victims to do so could further traumatize them. Further research in needed to generate knowledge on human traffickers' profiles to inform trafficking in persons control programs through HIV and AIDS interventions in Tanzania. PMID- 22066291 TI - Utilization of alternative medical services by people of a north central city of Nigeria. AB - INTRODUCTION: The use of alternative therapies is becoming more popular in the recent times especially due to the increasing cost, distrust and limitations of modern western medical care. There is a universal trend toward naturalness and herbal medicine is now being modernized and being accepted by people who would not have used them. This community based study seeks to assess the prevalence, pattern, behaviour and determinants of AT use. MATERIALS AND METHODS: It was a cross-sectional descriptive survey among adults in the Ilorin city of Nigeria. Participants were selected by multistage sampling and information obtained by the use of semi-structured questionnaire. RESULTS: Total prevalence AT use was 67.7% while total prevalence of indigenous and foreign AT use was 44.8 and 30.4% respectively. Among indigenous AT users, 87.5% will use both conventional and modernized type while 12.5% will use only the modernized type. More than 10% were new users of AT. Respondents use AT for promotive, preventive and curative purposes. Only 3.5% were considered as safe users according to 9-point items. The male respondents and the never married ones practice a safer use of alternative therapy (p<0.05). Similarly, the respondents with higher educational status also have a safer practice of AT use (p<0.05). CONCLUSION: There is high prevalence but unsafe AT use in Ilorin. There should be intensification of regulation of advertisement and sales of unwholesome herbal medicines. Further research to integrate the practice into modern healthcare is recommended. PMID- 22066292 TI - Immunogenicity and efficacy of Hoshino strain of mumps vaccine in Iran; two years study. AB - This report describes the immunogenicity and efficacy and long term immunity of Hoshino strain of Mumps (included in MMR Vaccine) in shahr-e-kord, Islamic Republic of Iran (I.R.Iran). A total of 338 Children aged 3-18 years were tested for Mumps IgG using enzyme-linked immunosorbent assay (ELISA). The proportion of susceptible, mumps IgG negative, children was 19.8% (67 subjects). Of the 67 susceptible children, 36 received the MMR vaccination and successfully completed the study. Blood was collected by venipuncture 3, 12, and 24 months after vaccination and serum samples were tested by ELISA for detection of Mumps IgM and IgG. The overall seroconversion rate was 86.1%, 77.7% and 75% at 3, 12, and 24 months after vaccination respectively. PMID- 22066293 TI - Elemental profile in amniotic fluid of some Nigerian pregnant women. AB - In this study concentration level of calcium, cadmium, copper, iron, magnesium, manganese, nickel, lead and zinc were determined in the amniotic fluid of pregnant women, aged 15 - 45 years enrolled at the Obafemi Awolowo University Teaching Hospitals Complex Ile - Ife. This was with a view to predict the body burden of the metals in the pregnant women and assess the health implications of the toxic elements to the pregnant women and their fetuses. Fifty samples of the amniotic fluid were collected from the pregnant women. The efficiency of extraction of trace metals using conventional wet acid digestion method (CDM) and microwave induced acid digestion method (MWD) was determined by recovery experiments. Levels of trace metals were determined using Atomic Absorption Spectrophotometry. The high percentage recoveries obtained from MWD made it a more efficient method than the CDM and hence its adoption for sample digestion. Statistical analysis of data using descriptive and inferential statistics revealed that age; education and profession have effects on the levels of the trace metals. The mean levels of most of the toxic metals obtained in this study were lower than the recommended limits of trace metals in women whole blood. PMID- 22066294 TI - Knowledge, attitudes and practices relating to malaria in a semi-urban area of Cameroon: choices and sources of antimalarials, self-treatment and resistance. AB - BACHGROUND: Malaria is a major public health problem in sub-Saharan Africa where it kills a child below five years ever 30 seconds. In Cameroon, malaria accounts for 40-45% of medical consultations, 57% of hospitalization days and 40% of mortality among children below 5 years. Community knowledge, attitudes and practices can enhance the fight against this disease. OBJECTIVE: To make a local analysis of the malaria problem and to establish epidemiological and behavioural baseline data and their implications for malaria control. METHODS: The study design was an observational community-based cross-sectional study in a semi-urban setting. Two hundred and fifty three participants of different socio-demographic status took part in the study from among 350 contacted. A structured questionnaire was administered to volunteers. The respondent's consent was sought and gained and subjects who could not read or write or understand English language were communicated to in the local language. The questionnaire was administered by a trained interviewer according to the schedule of the respondent. The data was analysed using SPSS. RESULTS: Antimalarials commonly cited for malaria treatment were chloroquine (26.09%) and nivaquine (14.62%) and analgesics: panadol (22.92%) and paracetamol (12.25%) including native drugs (6.32%). One hundred and forty-one (55.7%) [95% confidence interval (CI): 49.58 61.82%)] participants practiced self-treatment of malaria. Only 26.09% participants knew the correct adult malarial dosage for chloroquine and/or nivaquine. One hundred and twenty five (40.41%) [95% CI: 34.36-46.46%] participants got their antimalarials from authorized sources. One hundred and twenty five (40.41%) participants indicated that they get their antimalarials from the health center, 27(10.61%) from the shop, 24(9.49%) from hawkers, 23(9.09%) from the open market and 16 (6.3%) from herbalists. Only 66 (26.09%) [95% CI: 20.67-31.50%] participants knew the correct adult dosage for chloroquine or nivaquine treatment of malaria. Eighty five (33.6%) [95% CI: 27.78-36.57%] participants had correct knowledge of malarial resistance. Of the 85 (33.6%) participants who had knowledge of malaria resistance, 52(20.55%) ascribed malaria resistance to continuous fever for a long time during treatment, 15 (5.93%) to serious fever during treatment and 18 (7.12%) when chloroquine does not stop the malarial fever. Most (27.06%) of those who had the correct knowledge of malarial resistance were in the age group 31-35 bracket compared with other age groups (P>0.05). There was no difference in correct knowledge of malarial resistance and participant's professions. CONCLUSION: Malaria self-treatment is common but knowledge of malaria resistance is poor. This method should be improved upon by giving correct information on the dosage of adult malaria treatment on radio, television, posters and newspapers because banning it will push many people to use it in hiding since it has its advantages. Malaria drug abuse can lead to drug resistance hence in-vitro and in-vivo tests are warranted to confirm malaria resistance. PMID- 22066295 TI - You cannot prevent a disease; you only treat diseases when they occur: knowledge, attitudes and practices to water-health in a rural Kenyan community. AB - OBJECTIVE: Almost 1 billion individuals lack access to improved water supplies, with 2.6 billion lacking adequate sanitation. This leads to the propagation of multiple waterborne diseases. The objective of this study was to explore local knowledge, attitudes and practices to understand the mechanisms and pre conditions for sustainable uptake and use of these facilities. METHODS: Data collection took place in a rural Kenyan community in September 2009. A qualitative approach was taken, with 4 focus groups and 25 in-depth interviews conducted. Participant characteristics varied by age, gender, education, marital status, employment and community standing. RESULTS: Few participants reported current access to improved water and sanitation facilities. Though they expressed desire for latrines and water sources, barriers including lack of funds and social capital, decrease the ability for installation. Participants understood that there was a link between the quality of water and their health, however, perceived benefits of current contaminated sources outweigh the potential health impacts and proliferate their continued use. CONCLUSION(S): While water-health links are understood to varying degrees within the community, contextual (physical environment), compositional (individual) and collective (community) factors interact to influence health. Community challenges, such as lack of unity, lack of education and lack control were identified as the main barriers to initiating change, despite a desire for increased access to safe water and sanitation. PMID- 22066296 TI - Soaps and germicides as adjunct topical antimycotic agents on candida species implicated in vulvovaginal candidasis. AB - OBJECTIVE: The study aims at evaluating the potentials of soaps and germicides/disinfectants as adjunct topical anti-vulvovaginal candidasis agents. METHODS: In vitro inhibitory activities of the test agents, prepared according to the manufacturer's specification for toilet and midwifery purposes were determined using modified agar well-diffusion method. RESULTS: Varied susceptibility patterns were exhibited by Candida albicans (26.5%), C. glabrata (18.4%), C. pseudotropicalis (14.3%) and C. tropicalis (40.8%) implicated in vulvovaginal candidasis, indicating Crusader oil (100%), Meriko (95%), Tetmosol (84.7%) and Aloe (68.4%) as the most inhibitory soaps against the Candida strains. The in vitro inhibitory activities of the germicides and disinfectants ranged between (Dettol; 34.6% and Purit; 84.6%) for C. albicans; (Roberts; 33.3% and Purit; 83.3%) for C. glabrata; (Roberts; 21.4% and Purit; 92.9%) for C. pseudotropicalis; (Dettol; 35.0% and Purit; 87.5%) for C. tropicalis respectively. All the Candida strains were totally inhibited by the germicides and disinfectants at the second lower dilutions, except in Morigad towards C. albicans (69.2%]) C. glabrata (72.2%), C. pseudotropicalis (92.9%) and C. tropicalis (82.5%) but none of the vaginal Lactobacillus strains was inhibited by the soaps, germicides or disinfectant. About 90% of a control group indicated relief after pubic cleansing with soaps, germicides and disinfectants. CONCLUSION: Results indicatied the safety of soaps, germicides and disinfectants as potential adjunct topical cleansing-agents in cases of vaginal itching and candidasis, a common mucosal infection caused by opportunistic yeasts of the Candida genus. PMID- 22066297 TI - Self-percieved need for dental care: a questionnaire study. AB - AIM: To assess the prevalence of perceived need of problem based dental care. OBJECTIVES: - To evaluate the self-perceived need for dental care in general population.To assess the need for any type of dental care in general population of Belgaum city.To assess the need of general dental check-ups. METHODOLOGY: A convenient sample of 300 in the range of 20-60 years of age was randomly selected from general population of Belgaum city. The questionnaire consisted of general information of the respondent like name, age, sex, address .The respondents were asked to mark the answers, confidentiality of the results is assure. RESULTS: More number of males are in a need of dental treatment than compared to females .Many people think that their teeth need to be cleaned by dentist. CONCLUSION: The findings indicate that although most of the people were not satisfied with condition of oral health and describe their condition of teeth as fairly poor and mostly visited the dentist when they are in pain. Most of the population do neither have appointment to see a dentist nor they ought to go to a dentist for check up very soon .Many people think that their teeth need to be cleaned by dentist. PMID- 22066298 TI - Influence of percieved body image on nutrient intake and nutritional health of female students of Moi University. AB - OBJECTIVES: Issues related to dietary patterns and body image concerns have been among western cultures. It would therefore be inappropriate to use these findings as a basis of intervention in developing countries because this is an emerging issue in developing countries. Although this situation may be in Kenya, there is no data to quantify it and thus the need for research in this area. The main objective of this study was to investigate the perceived body image of Moi University undergraduate female students and its influence on their nutrient intake and nutritional health. METHODS: Cross sectional Survey was done on 260 female students of Moi University aged 20-25. Stratified followed by systematic sampling was used to get the sample. Questionnaires were used to collect data. Measurements of weight, height and mid-upper arm circumference were taken by the researcher using standardized procedures and equipments. SPSS was used for data analysis. Descriptive statistics were used to summarize data. Chi square tests, t tests and logistic regression were further done. RESULTS: It was found that most of the respondents with positive (69%) and negative (75%) body image were not comfortable with overweight. The mean BMI was 21.73 +/- 3.03 kg/m2 and MUAC was 26.55 +/- 3.15 cm. Prevalence of underweight and overweight based on BMI was 46% and 9% respectively. Mean intakes of energy, protein, vitamin A and iron were, 1245.92 kcals/day, 36.99g/day, 368.29 RE/day and 12.6g/day respectively. Factors associated with adequacy of nutrient intake were knowledge on food choice and irregular meal patterns. CONCLUSION: There is need for nutritional counseling and education among university students to address the issue of body image vis a viz food intake since most students skipped meals and this together with knowledge on food choice were found to significantly predict nutrient intake and body image perceptions. PMID- 22066299 TI - Awareness of information, expectations and experiences among women for obstetric sonography in a south east Nigeria population. AB - BACKGROUND: The role of obstetric sonography in the development of diagnostic ultrasound technology has remained invaluable in obstetric and gynaecological investigation. OBJECTIVES: This work investigated the awareness of information, expectations and experiences of pregnant women coming for obstetric sonography. METHODS: One hundred and ten (110) pregnant women in Anambra State of Nigeria were prospectively studied during prenatal ultrasound scan. RESULTS: The mean age of the studied population was 30.5 +/- 14.5 years. Majority (85%) of the subjects were already aware of obstetric ultrasound scan. Most of the subjects were between the ages of 26-35. 73% got their information from antenatal centre. Over 20% were interested in the lies and presentation of their foetus. During the scan, about 69% subjects interested with the sonographers, and more than half of the population (51%) saw their babies. CONCLUSION: The role of prenatal a sonography in obstetric care should be promoted by creating awareness campaign in antenatal centres, and initiating mother/sonographers interaction are necessary. PMID- 22066300 TI - Validity of the WHO criteria for adolescent hypertension. AB - BACKGROUND: WHO Second Task Force Criteria of adolescent hypertension (95th percentile for age) has been use for a long time and different studies have indicated wide variation of hypertension through out the world. OBJECTIVE: To find out the validity of the WHO diagnostic criteria for adolescent hypertension. METHODS: A cross-sectional study was undertaken in an urban slum of Chetla, Kolkata, among 1081 adolescent population (10-19 yrs of age). Initially 95th percentile values for age of systolic and diastolic blood pressure were calculated in different age groups and comparison was made between hypertensive subjects identified by the study values and the WHO reference values, using sensitivity and specificity parameters. RESULTS: In all the different age groups, the diagnostic criteria of hypertension in the study had sensitivity 100%, but specificity varied in the different age groups i.e. 95.34% (10-12 years), 93.89% (13-15 years), 97.41% (16-18 years), 95.34% (10-18 years) and 100% (19 year). CONCLUSION: Age specific reference values for blood pressure of adolescents should be formulated locally in different regions to aid in the identification of children with high blood pressure. PMID- 22066301 TI - Environmental pollution of lead in traffic air and blood of traffic policemen in Khartoum State, Sudan. AB - INTRODUCTION: A cross sectional study was conducted in Khartoum State. A total of 45 males' traffic policemen were divided into two groups according to exposure to car exhaust; n=30 taken as exposed group, n=15 taken as controls, who were not exposed to car exhaust. OBJECTIVES: The study was conducted to determine lead concentrations in traffic ambient air, to determine lead levels in blood of traffic policemen, and to evaluate the effect of exposure to car exhaust on traffic policemen during January 2009. METHODS: The level of lead in ambient air was determined in 14 locations which were taken randomly at the intersections and entrances to the bridges using personal sampler "Cassella, U.K". The blood samples of all policemen were analyzed by atomic absorption Spectrophotometer to determine lead levels. A questionnaire was designed to assess the adverse health effects on the traffic policemen. RESULTS: The degree of environmental lead pollution in traffic ambient air was found to be 0.1937 +/- 0.1768 mg/m3 with range between 0.000-0.5166 mg/m3. In seven locations out of fourteen locations lead concentrations were 0.1940 and 0.5166 above the permissible level of 0.15 mg/m3 permitted internationally. Blood lead levels on traffic policemen (exposed and control groups) were found to be 2.4691 +/- 1.4065 microg/100 ml and 0.3944 +/- 1.2471 microg/100 ml respectively and there is no significant differences between the two groups where using SPSS program. A questionnaire findings were: average age mean of 35.9 +/- 7.7 years, 47.48% worked for periods of more than 20 years, 74.19% did not work before joining the traffic police, 51.6% of them recognized traffic air pollution as a problem of high level, 45.2% of them estimated it as medium, and 3.2% as low. As habits 38.71% were smokers, and for health complaints, 61.29% have various complaints of headache, fatigue, abdominal, hypertension and anemia. All these symptoms have a close relationship with lead poisoning. CONCLUSION: When we compared the results of age groups and work duration with lead levels of blood samples the results was not significant. PMID- 22066302 TI - Attitudes and practices on HIV preventions among students of higher education institutions in Ethiopia: the case of Addis Ababa University. AB - The main objective of this cross-sectional study is to assess higher education students' attitudes, their practice on preventive measures against HIV/AIDS; and examined factors affecting attitude and practice of the students related to HIV/AIDS prevention. The 606 study participants were drawn from Addis Ababa University, which is the oldest and biggest public university in Ethiopia, through multistage sampling. Data were collected using survey quantitative (questionnaire) and qualitative (FGDs), and subsequently, analysis of the data was made through the use of descriptive statistics (Frequency and logistic regression model). The findings of the study revealed that 207 (34.2%) of respondents were sexually active during the survey. Of these, 144 (23.8%) of them had sexual intercourse with their partner or someone in the last 6 months. The mean and median age at first sex debut was computed as 17.8 and 18.0 years respectively. About 489 (80.7%) did not perceive being at risk of contracting HIV/AIDS. But 65.5% of the respondent had favorable attitude on HIV prevention. 359 (59.2%) of the respondents had experienced at least one of the three HIV prevention practice. Of which, more than half (52.4%) adopted abstinence as top preventive measure. The result also showed that out of the total respondents 47.2% had been tested for HIV/AIDS and more than 80% have willingness to take VCT service for HIV/AIDS. As to the multivariate analysis result; sex, previous residence, religious participation, pornographic viewing, currently alcohol intake, chewing khat and cigarette smoking were found to be determinant of AAU students' attitude on HIV prevention. Similarly, age, having pocket money, pornographic film show and currently khat chewing were determinants of practices on HIV prevention. Finally, based on the findings, the study has forwarded some workable recommendations. PMID- 22066303 TI - Emergence of dengue virus serotype 3 on Mayotte Island, Indian Ocean. AB - A serosurvey carried out in 2006 in Mayotte, a French overseas collectivity in the Indian Ocean, confirmed previous circulation of dengue virus (DENV) on the island, but since the set up of a laboratory-based surveillance of dengue-like illness in 2007, no case of DENV has been confirmed. In response to an outbreak of DENV-3 on Comoros Islands in March 2010 surveillance of dengue-like illness in Mayotte was enhanced. By September 15, 76 confirmed and 31 probable cases of DENV have been identified in Mayotte. In urban and periurban settings on the island, Aedes albopictus is the predominant Aedes species, but Ae. aegyptii remains the most common species in rural areas. Given the epidemic potential of dengue virus in Mayotte, adequate monitoring including early detection of cases, timely investigation and sustained mosquito control actions remain essential. PMID- 22066304 TI - Antenatal care and morbidity profile of pregnant women in an urban resettlement colony of Delhi, India. AB - CONTEXT: The burden of antenatal morbidities and health care services utilization during antenatal period serve an important role in defining service needs and to assess reproductive health status of women. OBJECTIVES: To evaluate the burden of antenatal morbidities in women and to assess the health care utilization by study subjects during antenatal period. MATERIALS AND METHOD: A community based follow up study was carried out in an urban resettlement colony of Delhi. All pregnant women in the study area were enrolled and followed for two more visits to collect information about morbidities suffered and health care services utilized during pregnancy. Appropriate tests of significance were applied. RESULTS: Of 358 women enrolled, three hundred could be followed for two more visits. Majority of women (80.3%) suffered one or more morbidities during their current pregnancy but overall care sought for illness during pregnancy was poor. Visits for routine preventive check up was made by most of women (95% and above) but recommended three antenatal visits was significantly low among women of age more than thirty (OR=16.6; 2.2-125.9), of lower middle socio economic status (OR=2.84; 1.16-6.93) and parity three or more (OR=4.37; 1.07-17.83). Women with education status of high school and above had significantly lower odd ratio (OR=0.33; 0.11-0.99) for having less than three antenatal visits. CONCLUSIONS: Care sought for antenatal morbidities is still poor among women of urban resettlement colonies and age, parity and education of women has a significant bearing on antenatal visits. PMID- 22066305 TI - Asthma, atopy and COPD in sub-Saharan countries: the challenges. AB - Asthma and COPD are the most important chronic airways diseases worldwide. Urbanization and westernization of African countries are important factors for the development of chronic respiratory diseases. Unfortunately for many reasons, only few studies on atopy, asthma and COPD have been carried out in Africa and risk factors are not well known on the continent. Moreover, in many African countries drugs for asthma and COPD are either lacking or expensive. There is a need for setting up clear strategies to stop progression of asthma and COPD by reducing risk factors such as tobacco consumption and environment pollution. PMID- 22066306 TI - A comprehensive review of diverse issues related to sickle cell disease. AB - OBJECTIVE: This review was carried out to understand diverse issues in sickle cell disease (SCD), such as its prevalence, clinical manifestations, preventive measures, secondary infections, nutrition and therapies. METHODS: A deductive reasoning approach was followed to unearth the information from the published literature. Vast amount of resources (online and offline) were referred to collect and analyse the content related to SCD. The research publications were analysed following the standard content analysis procedures. RESULTS: The study results revealed a dearth of literature. The available information seems inconclusive due to the local nature of the disease, the high prevalence in the developing world where the accessibility to healthcare is a big issue. The prevalence data is scarce; the studies conducted so far reveal a very small sample size making the generalization of results difficult. CONCLUSION: The review of literature for diverse issues related to Sickle cell disease (SCD) revealed varied aspects to address the SCD related issues. Although there are reports that provide interesting insights of SCD, majority of them are inconclusive. The prevalence reported by different authors varies significantly that warrants initiation of a comprehensive SCD screening programme. The pathophysiological changes in the patients with SCD present a challenging and dynamic situation, which needs to be studied in more details. The many clinical complications reported by different authors call for a more concerted effort for additional understanding. Furthermore, the studies conducted so far are found to have very less sample size, especially in light of the prevalence estimates reported by various authors. The review indicates the important aspects of SCD that are to be addressed in urgency such as follow-up of newborns screening tests, stroke prevention, pregnancy complications, pain prevention, morbidity and mortality studies, and genetic studies for the better life of people with SCD. PMID- 22066307 TI - DES: an ongoing disaster. PMID- 22066308 TI - Quetiapine. A me-too neuroleptic; no panacea. AB - Quetiapine, a so-called atypical neuroleptic, is authorised in the European Union for use in the standard indications of neuroleptics. However, it is the only neuroleptic licensed for the treatment and prevention of depressive episodes in patients with bipolar disorder, and as add-on therapy for depressive episodes inadequately improved by an antidepressant. In patients with schizophrenia, the authors of two meta-analyses, one including 12 trials (3443 patients) and the other 21 trials (4101 patients), concluded that quetiapine was not clearly more effective than other conventional or atypical neuroleptics. In bipolar patients with manic episodes, the results of two trials suggest that quetiapine monotherapy is not more effective than haloperidol or lithium. Two placebo controlled trials of add-on quetiapine therapy in patients receiving a mood stabiliser (lithium or divalproate sodium) yielded conflicting results. In bipolar patients with a depressive episode, the only available trial, versus placebo and versus paroxetine in 740 patients, failed to provide conclusive evidence. In two trials with controversial designs, in which quetiapine was added to a mood stabiliser in order to prevent new depressive or manic episodes in bipolar patients, quetiapine appeared to be more effective than placebo: about 15% to 20% more patients were stabilised on quetiapine than on placebo. There are no trials to show whether quetiapine is more effective in preventing manic episodes than a neuroleptic. In a trial including 1226 patients in whom quetiapine was effective during a first depressive or manic episode, quetiapine appeared to be more effective than lithium in preventing a depressive episode (relapse rate 8.9% versus 13.5%) but not a manic episode. These comparisons may be biased, however. Two placebo-controlled trials assessed quetiapine add-on therapy in patients in whom an antidepressant was inadequately effective. The conflicting results obtained in these two trials rule out drawing firm conclusions as to the efficacy of quetiapine. Overall, quetiapine has the adverse effect profile common to atypical neuroleptics. However, hypercholesterolaemia is more frequent than with risperidone, and both clinical trials and post-marketing data have shown that quetiapine carries a risk of hypothyroidism. Animal studies suggested a risk of cataracts, but this adverse effect has not yet been confirmed in humans. The risk of sudden cardiovascular death appears similar to that reported with other neuroleptics. A retrospective survey suggests that the consequences of acute overdose are more severe with quetiapine than with other neuroleptics. Quetiapine is metabolised by cytochrome P450 isoenzyme CYP3A4, creating a high risk of pharmacokinetic interactions. In practice, quetiapine has not been shown to provide a therapeutic advantage over other treatments, although additional trials in the prevention of depressive episodes are warranted in selected patients. PMID- 22066309 TI - Fondaparinux and isolated superficial-vein thrombosis. Of little interest. AB - No proven decline in mortality; no tangible prevention of pulmonary embolism; beware of bleeding. PMID- 22066310 TI - Omalizumab 75 mg. Whatever the dosage, the drug should be avoided in severe persistent asthma. PMID- 22066311 TI - Onsenal: marketing authorisation withdrawn in the European Union. Company failed to supply required data. PMID- 22066312 TI - INN common-stem: -conazole. PMID- 22066313 TI - Psychological consequences of DES exposure in utero. AB - Between the 1950s and the late 1970s, millions of women worldwide took diethylstilbestrol (DES) during pregnancy. It was claimed that DES prevented miscarriage, even though a clinical trial was interrupted in 1953 when an interim analysis showed no beneficial effect in the prevention of miscarriage. In 1971, it emerged that DES exposure in utero was associated with somatic effects in adulthood, including female genital abnormalities with obstetric consequences, vaginal cancer, and male urogenital disorders. This article examines the psychological effects of exposure to DES in utero, based on a review of the literature using the standard Prescrire methodology. In two experimental studies, mice exposed to DES during gestation were found to be more aggressive than unexposed mice. A randomised clinical trial and epidemiological studies have pointed to a risk of psychological disorders during adolescence and adulthood after DES exposure in utero. A placebo-controlled randomised trial of DES was conducted in London in the 1950s but was never published. In the 1980s, a research team recovered some of the original data and obtained information on the adult health status of the persons exposed in utero. Compared to the placebo group, psychological disorders were twice as frequent in the adults who were likely to have been exposed to DES in utero. Three large epidemiological studies were also conducted. One study showed that major depressive episodes were about 1.5 times more frequent in women exposed to DES in utero than in unexposed women; the second showed that exposed women had an episode of major weight loss more often than unexposed women; while the third showed no significant difference between the groups in terms of depressive episodes. Smaller studies also suggest that depressive episodes tend to be more frequent after DES exposure in utero. In practice, these data suggest that persons exposed to DES in utero have an increased risk of experiencing psychological disorders and should be monitored accordingly. PMID- 22066314 TI - Exenatide and sitagliptin: pancreatitis and pancreatic cancer. Harms on the rise. PMID- 22066315 TI - Dutasteride: high-grade prostate cancer. Risky in prostate cancer prevention. PMID- 22066316 TI - Tadalafil: visual and auditory disorders. Inform patients of these risks. PMID- 22066317 TI - Analgesia for terminally ill adult patients. Preserve quality of life. AB - Adequate pain management is crucial in maintaining the best possible quality of life for terminally ill patients. This article examines pain management in the palliative care setting, based on a review of the literature using the standard Prescrire methodology. Accurate pain evaluation, preferably by the patient, is essential for guiding treatment decisions. Some causes of pain are amenable to specific treatments. The expected benefits and harms of the various treatment options and procedures must be weighed on a case by case basis. Quality of life should always be the first priority. The World Health Organization has developed a "three-step analgesic ladder", based on the use of increasingly potent analgesics: step I analgesics include paracetamol and nonsteroidal anti inflammatory drugs (NSAIDs); codeine is the standard step II analgesic; and morphine is the standard step III analgesic. Fentanyl is an alternative to morphine. The daily morphine dose must be determined for each patient. Morphine titration starts with oral doses given every 4 hours, but additional doses can be taken every hour if necessary. Total consumption is then used to calculate the dose required the following day. A sustained-release product can be used to reduce the number of doses required when a consistently effective daily dose has been established. When patients are unable to take morphine orally, it can be given by subcutaneous injection, and by subcutaneous or intravenous infusion. Pumps allow the patient to self-administer morphine on demand. Fentanyl transdermal patches are another option for stable pain. Immediate-release oral forms and injections are useful for preventing or treating breakthrough pain. If morphine requirements increase during treatment, the most likely explanations are exacerbations of pain or an excessively long interval between doses. Pharmacological tolerance and psychological dependence are rare during palliative care. In case of renal failure, the morphine dose should be reduced, sustained release morphine should be replaced by immediate-release morphine, or morphine should be replaced by fentanyl, as fentanyl metabolism is only slightly affected by renal function. The main adverse effects of morphine are constipation, nausea and vomiting. Drowsiness is frequent at initiation of treatment. Respiratory depression is rare when morphine is introduced gradually. Tricyclic antidepressants and carbamazepine have acceptable harm-benefit balances in patients with neuropathic pain. Cannabinoids are another option but have not been adequately assessed. Localised refractory pain may respond to local anaesthesia, chemical neurolysis or surgical ablation. In practice, it is best to allow patients to control their own analgesic consumption, within limits set by their physician to prevent dosing errors. PMID- 22066318 TI - Simple cystitis: symptoms persist longer without antibiotics. AB - A randomised trial has shown that antibiotic therapy can be avoided in 20% to 25% of women with simple cystitis, with no increase in the risk of complications but with longer duration of symptoms. PMID- 22066319 TI - Analysing an adverse event in primary care: a multidisciplinary, collaborative process. AB - Beyond detecting a healthcare-related adverse event, in-depth analysis (to determine which elements were preventable) sometimes requires the collaboration of all the healthcare professionals involved in the patient's care. The objective of collective, multidisciplinary analysis of healthcare-related adverse events is to improve patient safety; it is an extension of personal "reflexivity" (the ability to reflect on one's own actions). A morbidity and mortality conference (M&MC) is a means of collectively learning through errors; its aim is improve professional practice and quality of care. This approach is mainly used in hospitals, but it can be used by all healthcare professionals, including those in primary care, based on working procedures to be developed by the group concerned. Collective analysis of adverse events can improve communication, teamwork and promote a culture of safety among healthcare professionals. The problems detected can be of relevance to all the healthcare professionals involved. PMID- 22066320 TI - European Medicines Agency: an unacceptable choice. PMID- 22066321 TI - Public knowledge, attitude and perception of over the counter medicines: case study in Dar es Salaam region, Tanzania. AB - OBJECTIVES: The purpose of this study was to investigate on misuse, abuse and the general public opinion as well as perception of OTC medicines. METHODS: Data were collected, by face-to-face interview guided with a semi-structured questionnaire. The key questions focused on community attitude towards retail pharmacy, use of OTC medicines, views on OTC in terms of safety and effectiveness and knowledge and opinion on misuse and abuse of OTC medicines. The collected data were coded and statistically analyzed using EPI-Info version 6 database. RESULTS: Out of 270 interviewees, 50% admitted to have had visited retail pharmacies at least once per month. More than half of the participants (64.1%) reported to having been buying OTC medicines at least once in a month and 55.7% used the medicines as per containers label or leaflets' instructions The public demonstrated high awareness on the potential misuse of OTC medicines. CONCLUSION: The study revealed a high level of awareness on the potential abuse of OTC medicines and positive perception with regard to safety and effectiveness of OTC medicines. From these findings, it shows those pharmacists need to be more proactive in the management of inappropriate OTC drug use. PMID- 22066322 TI - Is Nottingham Health Profile a reliable tool to measure quality of life of Filipinos with chronic kidney diseases undergoing hemodialysis. AB - The quality of life (QOL) of hemodialysis patients is often compromised and many tools have been developed to assess the health-related QOL of chronic kidney disease (CKD) patients undergoing hemodialysis. However, no such tool is currently in use in the Philippines. The objective of this study is to determine if Nottingham Health Profile (NHP) can be a useful tool in the Philippines. Eighty patients undergoing hemodialysis in the dialysis unit of our hospital were enrolled for this study. Sixty-nine patients completed the study. Comparative analysis revealed significant difference in social isolation with favorable result for the Filipino patients. Other measures correlate well although with differences that were not statistically significant. NHP can be successfully applied as a standard QOL tool in the Philippines. However, it should be translated into Filipino to avoid language difficulty. NHP may be recommended for QOL determination in other developing countries. PMID- 22066323 TI - Teenagers must think about healthy living. AB - The aim of the current study was to investigate the impact of promoting health through talks and workshops, to students at schools and colleges. We believe that this would impact on designing a dynamic curriculum for training health/medical students in a higher education setting. Schools and colleges in the region were contacted with the prospect of offering free health promotion service by qualified academics from a higher education establishment. Questionnaires were distributed prior to the start of the talks and were collected at the end. The talks focussed on smoking, drug and alcohol abuse, healthy eating and STD's. The results showed that the interest, originality and impact factor were high for all talks. The comments obtained from students reflected the need for an external organisation to deliver such talks. The method of delivery and the content of the talks also contributed to the high interest factor. It is therefore essential that a health/medical curriculum should reflect the need for health professionals to work interprofessionally in order to help deliver effective health promotion programmes to schools and to the wider community. PMID- 22066324 TI - Assessment of the protective effect of male circumcisioin from HIV infection and sexually transmitted diseases: evidence from 18 demographic and health surveys in Sub-Saharan Africa. AB - A cross-sectional comparative study based on secondary data of 18 Demographic Health Surveys (DHS) carried out in Sub-Saharan Africa starting from 2003 was conducted to assess the protective effect of male circumcision from HIV infection and STDs. From all surveys, information on 70,554 males aged 15-59 years was extracted. The association between male circumcision and HIV infection and STD symptoms (Genital discharge or genital ulcer/sore) was assessed using binary logistic regression. Adjustment was made for sexual history and basic sociodemographic variables. The weighted prevalence of HIV among men 15-59 years was 3.1%. In the bivairate analysis being uncircumcised was significantly associated with risk of HIV with Odds Ratio (OR) of 4.12 aged (95% CI: 3.85 4.42). The association was even more significant, 4.95 (95% CI: 4.57-5.36), after adjustment for number of lifetime sexual partners and socio-demographic variables. The risk associated with uncircumcision is significantly lower among younger men aged 15-29 years than those in 30-59 years age category. About 5.5% of the study subjects reported either genital discharge or genital sore/ulcer in the preceding 12 months of the surveys. Circumcision was not significantly associated with either of the symptoms of STD with adjusted OR of 1.07 (95% CI: 0.99-1.15). The study concludes that male circumcision provides a strong protection against acquisition of HIV infection. Hence, it can be considered as a possible way of reducing the spread of HIV infection in areas where the practice is rare. A comprehensive study to assess the association between circumcision and different types STDs is recommended. PMID- 22066325 TI - Prevalence and factors influencing consistent condom use among sexually active young people attending a youth friendly centre in Kenya, 2008. AB - OBJECTIVES: Young people in Kenya engage in unprotected sexual intercourse with resultant high rates of unwanted pregnancy, STIs and HIV infection. To formulate effective and acceptable approaches that encourage safer sexual behavior, we need to understand young people sexual behavior. We thus conducted a study to determine prevalence and factors influencing consistent condom use among youths in Kenya. METHODS: We carried out a cross-sectional study at the Youth Friendly Centre of Provincial General Hospital in Nakuru town. A self-administered questionnaire was used to collect data from persons aged 15 to 24 years using systematic random sampling method. Subjects who self reported positively on all three variables i.e." ever condom use", "condom use within the last three months", and "condom use during the last sexual encounter" were defined as "consistent condom users". Data analysis was performed using Chi-square test with alpha level of significance at 0.05. RESULTS: Among the 223 enrolled subjects 196 (87%) were sexually active. The prevalence of consistent condom use was 36%. independently promoters of consistent condom use were; talking with parents about condom (OR = 2.65; 95% CI = 137-5.12; p = 0.004); attaining college level education (OR = 2.55; 95% CI = 132-4.94; p = 0.006) and having multiple sexual partners (OR= 2.05; 95% CI = 1.01-4.16; p = 0.048). Belief that condom diminishes pleasure (OR = 0.50; 95% CI = 0.26-0.96; p = 0.037) and last sexual partner being a spouse (OR = 0.36; 95% CI = 0.13-0.97; p = 0.044) were independent hindrances to consistent condom use. CONCLUSIONS: Majority of youths are sexually active with few of them not consistently using condom. Parents should be informed on the sexual behavior of the youth inorder to discuss about safer sexual behavior with their youths while encourage abstinence or postponement of sexually activity. Youth peer education need to be strengthened to foster safer sexual behaviors. PMID- 22066326 TI - Examining household possession and willingness to pay for the retreatment of ITNs with insecticides among local residences in a malaria endemic area. AB - OBJECTIVE: To examine the household possession and willingness to pay for the retreatment of ITNs with insecticides among local residences in a malaria endemic area of Ethiopia. METHODS: A descriptive cross-sectional study was conducted between October 2008 and December 2008 using a pre-tested questionnaire in Azendabo town, Ethiopia. 246 household members were interviewed on the household possession and willingness to pay for the retreatment of ITNs with insecticides. RESULTS: Over all, 96.3% of the respondents had awareness about ITNs. 90.2% had heard about ITNs retreatment with insecticides. However, merely 53.2% of the respondents were willing to pay for ITNs retreatment. Chi-square results revealed a strong association between respondents average monthly income and number of ITNs possessed per household (chi2 = 29.53; p = 0.005; df = 9). Similarly, the association between educational status and frequency of ITNs utilization was statistically significant (chi2 = 13.99; p = 0.029; df = 6). In addition, the chi square results shows close association between respondents economic status and willingness to pay for ITNs retreatment (chi2 = 12.16; p = 0.006; df = 3). CONCLUSION: Indeed, ITNs are one of the most powerful weapons in the fight against vector-borne diseases particularly malaria in sub-Saharan Africa. The efficiency of ITNs can be enhanced substantially by means of retreatment with insecticides. However, the present study results suggest that nearly half of the respondents were not willing to pay for ITNs retreatment due to lack of their affordability. Therefore, insecticide retreatment campaign should be initiated at free of cost at least yearly once in order to reduce the unbearable burden of malaria. PMID- 22066327 TI - Risk factors associated with cholera in Harare City, Zimbabwe, 2008. AB - OBJECTIVE: Two suspected cholera cases at Beatrice Road Infectious Diseases Hospital were reported to Harare City Health Department on 14 October 2008 setting in motion investigation and control measures. We determined the extent of the epidemic and risk factors for contracting cholera. METHODS: An unmatched 1:1 case-control study was conducted. CASE: Any resident of Harare City, 2 years and above, with acute watery diarrhoea, with or without vomiting from 30 October 2008 to 01 December 2008. CONTROL: Any resident of Harare City, 2 years and above, neighbour to a case, who did not contract cholera during the same period. RESULTS: From 14 October 2008 to 21 January 2009, 11203 cases were reported with a case fatality rate (CFR) of 3.98%. We interviewed 140 cases and 140 controls. Median age was 28 years (Q1 = 20; Q3 = 37.5) and 28.5 years (Q1 = 23; Q3 = 38) for cases and controls respectively. Having a diarrhoea contact at home [AOR = 12.02; 95% CI (5.46 - 26.44)], having attained less than secondary education [AOR = 4.40; 95% CI (2.28 - 8.48)]; eating cold food [AOR = 4.24; 95% CI (1.53 - 11.70)] were independent risk factors while drinking tap water [AOR = 0.05; 95% CI (0.03 - 0.11)], washing hands after using toilet [AOR = 0.19; 95% CI (0.09 - 0.39)]; eating hot food always [AOR= 0.29; 95% CI (0.17 - 0.49)] were independently protective factors. DISCUSSION: The high CFR may be due to poor case management and staff shortage in treatment camps. Th e cholera outbreak in Harare resulted from poor personal and hygiene practices that occur when water supplies are cut. Lack of water, low knowledge on cholera prevention measures and delays in community health education campaigns contributed to the protracted outbreak. Having a diarrhoea contact at home increases chances of household members acquiring infection. Provision of safe drinking water, community health education, recruitment of staff and training of health workers on cholera case management must be prioritized. PMID- 22066328 TI - Relationship between uninvestigated dyspepsia and body mass index: a population based study. AB - BACKGROUND AND AIM: Recent studies have shown inconsistent results about the association between body mass index and symptoms of gastrointestinal disorders. The aim of this study was to assess the association between body mass index (BMI) and symptoms of uninvestigated dyspepsia in patients with gastrointestinal symptoms and their relations with age. METHODS: This study was designed as a cross-sectional and population based evaluation that was conducted in Iran. The patients were interviewed by using questionnaire which was arranged on the basis of Rome III criteria for functional dyspepsia. The association between body mass index, age and dyspepsia symptoms was determined. RESULTS: A total of 790 patients with gastrointestinal symptoms (249 men, mean +/- SD of age, 49.9 +/- 19 years; mean +/- SD of BMI, 25.4 +/- 4.7) were included and among them 681 (86.2%) had symptoms of dyspepsia. The prevalence of dyspepsia symptoms among females younger and older than 50 years were 83% and 93.8% ,respectively, but these percentages among males younger and older than 50 years were 84.5% and 81.5%.In males younger and older than 50 years 42.9% and 37.6% had BMI over than 25, but these percentages were 51.3% and 54.8% for females. Among overweight and obese patients the prevalence of dyspepsia symptoms were 82.7% and 78%, respectively, compared with normal weight (90.7%). CONCLUSION: After the age of 50, the prevalence of dyspepsia symptoms and high body mass index were increased in females, but were decreased in males. No relation between symptoms of dyspepsia and body mass index in both genders was found. PMID- 22066329 TI - The story of abortion: issues, controversies and a case for the review of the Nigerian national abortion laws. AB - Abortion continues to be a major public health issue that evokes social, political, legal, cultural and religious sentiments and debates in all societies. This is particularly so in countries with restrictive abortion laws. It is one of the leading causes of maternal mortality and morbidity. Despite variations in the legal status of abortions in favor of restrictiveness in developing countries compared with developed countries, overall rates are quite higher in the developing countries. This review article therefore, examines the historical perspectives of induced abortion as well as the issues and controversies associated with induced abortion. Also, a review of the Nigeria national abortion law is made. We believe that this is capable of identifying useful interventions for designing programs that will lead to a reduction in the burden of unsafe abortion in developing countries. PMID- 22066330 TI - Assessment of water storage, treatment and use in the semi arid Kimana area, Oloitokitok district, Kenya. AB - OBJECTIVES: This study sought to identify the methods and associations of water storage, treatment and use among residents in the Kimana Fenced Area, Oloitokitok, Kenya for comparison with current best practices in order to develop recommendations to improve water sanitation issues in this area. METHODS: In a cross-sectional study design, 330 households were randomly selected and interviewed on water storage, treatment, and use practices. RESULTS: Eighty two percent of observed containers met CDC guidelines for improved water storage containers. Fifty seven percent of survey respondents reported not treating their drinking water, of which 49% indicated that they believed the water was already clean. Logistic regression showed that people who believed their water was unsafe were twice more likely to treat their water than those who perceived their water to be somewhat safe (p = 0.058). Those living outside the furrows were 56% less likely to treat their water in the home compared to those living along the furrow (p = 0.023). Respondents with a pastoral lifestyle were 69% less likely to treat their water than those with a non-pastoral lifestyle (p = .009). In terms of tribe, the largest treatment disparity was noted amongst the Maasai, with only 37.7% reporting any form of treatment. CONCLUSION: Tribe, pastoral lifestyle, proximity to the furrow and socio-economic status were found to contribute to water storage method and treatment within the Kimana fence. It is critical that these factors be addressed in future water storage and treatment interventions in this area. PMID- 22066331 TI - Prevalence of dental caries among elementary school attendees in Iran. AB - PURPOSE: The purpose of this study was to find out the dental caries status in six to nine years (6-9 years) old children. MATERIAL & METHODS: A total of 792 children including 396 girls and 396 boys were selected from several schools in Qazvin based on cluster sampling. Name, age, gender, address, and caries status each subject was recorded using a questionnaire. Intra-oral examinations were performed using a mirror and probes under suitable light-rays were not taken to diagnose the caries. RESULTS: Of a total of 792 children, 396 (50%) were males and the rest (50%) females. The dmft was 3.83, 3.57, 3.04 and 2.8 for aged six, seven, eight and nine respectively. The frequency of caries was higher in age group of six. The DMFT was 0.31 for each child. CONCLUSION: The present study showed that the frequency of caries was found to be higher than reported is unexpectedly high among the age group investigated in our research. According to the high prevalence obtained in our study, health recommendations on oral hygiene to target population and also parents and teachers should be made. PMID- 22066332 TI - Contraceptive knowledge, attitudes and practice among married women in Samaru community, Zaria, Nigeria. AB - Contraceptive use and fertility rates vary substantially among developing countries. In some sub-Saharan African countries, fewer than 10% of married women use contraception. Despite all efforts by governments to ensure availability of the products, prevalence has remained low. We conducted a community-based study to examine contraceptive knowledge, attitude and practice of family planning among married women in Samaru, Zaria, Nigeria. Multi-stage random sampling technique was used to study 200 women in Samaru community of Zaria, Nigeria. Mean age of the respondents was 30.6 +/- 1.5 years. In this study contraceptive prevalence was 12.5% and respondents had a positive attitude towards family planning. Thirty years after Alma Ata of which one of the components is to ensure maternal and child health (MCH) and family planning, contraceptive use in most of the communities in Northern Nigeria is low. There is urgent need to step-up public awareness campaigns on family planning to ensure wide spread acceptability and utilization among women within reproductive age group. PMID- 22066333 TI - Homicide of children in Dar es Salaam, Tanzania. AB - BACKGROUND: Although data are sparse, it has been estimated that the highest rates of homicide death amongst children are in Africa. Little information is available on ages 0-14 years. No known quantitative surveillance of early neonaticide (killed at less than one week) has been conducted previously in Africa. METHODS: A Violent Death Survey following WHO/CDC Guidelines was completed in Dar es Salaam region, Tanzania (population 2.845 million) in 2005. Qualitative and quantitative data were gathered and analyzed. RESULTS: The overall age adjusted rate of discarded and killed children in DSM was 2.05 per 100,000. The rate of early neonaticide was 27.7 per 100,000 while the rate of homicide incidence for children older than one week was 0.54 per 100,000 DISCUSSION: The overall estimated homicide rate for Africa of children under age 15 was 4.53 per 100,000. The rate in DSM was closer to the estimated global rate of 1.7 per 100,000. The results in DSM show that broad age groupings such as "< 1 year", "0-4 years" and "0-14 years" may mask a high incidence of neonaticide and an otherwise low incidence of murdered children. The print media provided good in depth coverage for a few cases but it is not known if the reported cases are representative. CONCLUSION: Eighty percent of homicides of children in DSM were neonaticides. Since it is believed that the forces behind neonaticide are fundamentally different than homicides of older children, it is suggested that data of future surveys be parsed to include neonates, until the phenomenon is more clearly understood and addressed. Further understanding of the mother and father of the deceased is needed. Continued surveillance data collection is important to expand the sample size. PMID- 22066334 TI - Environmental pollution of lead in traffic air and blood of traffic policemen in Khartoum State, Sudan. AB - INTRODUCTION: A cross sectional study was conducted in Khartoum State. A total of 45 males' traffic policemen were divided into two groups according to exposure to car exhaust; n = 30 taken as exposed group, n = 15 taken as controls, who were not exposed to car exhaust. OBJECTIVES: The study was conducted to determine lead concentrations in traffic ambient air, to determine lead levels in blood of traffic policemen, and to evaluate the effect of exposure to car exhaust on traffic policemen during January 2009. METHODS: The level of lead in ambient air was determined in 14 locations which were taken randomly at the intersections and entrances to the bridges using personal sampler "Cassella, U.K". The blood samples of all policemen were analyzed by atomic absorption Spectrophotometer to determine lead levels. A questionnaire was designed to assess the adverse health effects on the traffic policemen. RESULTS: The degree of environmental lead pollution in traffic ambient air was found to be 0.1937 +/- 0.1768 mg/m3 with range between 0.000-0.5166 mg/m3. In seven locations out of fourteen locations lead concentrations were 0.1940 and 0.5166 above the permissible level of 0.15 mg/m3 permitted internationally. Blood lead levels on traffic policemen (exposed and control groups) were found to be 2.4691 +/- 1.4065 microg/100 ml and 0.3944 +/- 1.2471 microg/100 ml respectively and there is no significant differences between the two groups where using SPSS program. A questionnaire findings were: average age mean of 35.9 +/- 7.7 years, 47.48% worked for periods of more than 20 years, 74.19% did not work before joining the traffic police, 51.6% of them recognized traffic air pollution as a problem of high level, 45.2% of them estimated it as medium, and 3.2% as low. As habits 38.71% were smokers, and for health complaints, 61.29% have various complaints of headache, fatigue, abdominal, hypertension and anemia. All these symptoms have a close relationship with lead poisoning. CONCLUSION: When we compared the results of age groups and work duration with lead levels of blood samples the results was not significant. PMID- 22066335 TI - Water risk factors pre-disposing the under five children to diarrhoeal morbidity in Mandera district, Kenya. AB - OBJECTIVE: The main causes of mortality and morbidity in Mandera are conditions related to inadequate water and sanitation such as diarrhoea, which has led to malnutrition and mortality among children under five years. This paper highlights the main sources of water in the district and identifies the water risk factors associated with diarrhoeal morbidity among these children. METHODS: A cross sectional descriptive study was carried out within the district, specifically in Khalalio, Central, Malkamari and Hareri divisions, the main respondents being caregivers from households where there was one or more children under the age of five. A sample size of 350 respondents from the households was interviewed using interview schedules. Other methods used were focus group discussions, observation and key informant interviews. RESULTS: Most of the respondents used the river as the main water source; however, there were differences in the divisions on the water sources. Often times, the water sources were not available throughout the year and the residents mainly depended on the river during times of drought. The river was as a result a major avenue for contamination. Most of the water sources were close to the households, but they used crude methods in transporting the water to the households, such as rolling jerricans on the ground. Less care was given to handling water at the household level, even after the poor means of transport, resulting in more children suffering from diarrhoea. CONCLUSIONS: The significant water risk factors as identified were the mode of water transportation, and the poor handling of water at the household level, including lack of or inappropriate water treatment methods. These, combined with the low education level further pre dispose the under five children to diarrhoea, thus calling for increased health education on safe water handling. PMID- 22066336 TI - Mortality among orthopaedic and traumatology admissions: a ten year review. AB - OBJECTIVE: Mortality in orthopaedic patients is not a common event. This study sets out to review the incidence and causes of mortality in orthopaedic and trauma admissions in a tertiary centre in a developing country. METHODS: Medical records of patients admitted to the Orthopaedic wards of the Obafemi Awolowo University Teaching Hospital, Ile-Ife over a ten year period (January 1999 December 2008) were retrospectively reviewed. The death certificates and postmortem examination findings were used in conjunction with the medical records to arrive at the possible cause of death in the deceased patients. Frequency analysis was done using SPSS version 13. RESULTS: Over this period, 2418 patients were admitted for orthopaedic and trauma with 84 deaths giving an overrall crude mortality rate of 3.47% (1.27% for paediatrics and 4.39% for the adults). Fourty nine patients (58.4%) died from trauma (fracture) related diagnoses followed by tumour (21, 25%) and infection (14,16.7%). Males were more affected 73.8% and the average age at death was 45.7years. Co-morbid conditions were found in 393% of the deceased patients. CONCLUSION: Trauma related deaths were the leading cause of mortality in our ward admissions and male patients at the prime of their lives were more often involved. Accident prevention and provision of facilities for appropriate management of trauma victims will help reduce substantially these untimely deaths in our world. The high incidence of co-morbid conditions emphasizes the role of multidisciplinary care in orthopaedic and trauma patients. PMID- 22066337 TI - Urban-rural estimation of hepatitis C virus infection sero-prevalence in north Central Nigeria. AB - BACKGROUND/OBJECTIVE: The epidemiology of hepatitis C virus (HCV) infection has been partially described for at risk groups in urban communities in Nigeria. On the other hand, literature on the possible spread of the virus in rural Nigeria remains extremely scanty. The objective of this study was to estimate the prevalence of HCV in a rural and urban community in Nigeria. METHODS: Four hundred and twenty four (n = 424) plasma samples belonging to 238 rural inhabitants and 186 urban dwellers in North Central Nigeria were tested for anti HCV markers using a third generation quantitative enzyme-linked immunosorbent assay (ELISA) that uses recombinant proteins and synthetic peptides derived from core and non-structural regions. RESULTS: 29(12.2%, CI = 0.17-0.86) of the rural samples and 5(2.7%, CI = 0.01-0.06) of urban samples were positive for HCV infection. The highest number of infections was in the 21-40 years age category. Our preliminary findings indicates that the number of HCV infection in rural was higher (p = 0.03) when compared with urban settings in Nigeria. CONCLUSION: Our results suggest a higher prevalence of HCV infection in rural than urban Nigeria in the region studied and possibly in Nigeria as a whole. HCV transmission is active in rural Nigeria and large scale studies to understand the dynamics of the infection are required so as to plan targeted preventive measures. PMID- 22066338 TI - Reimbursement changes coming--CMs key to meet payer requirements. AB - Case managers can have a big impact their hospital's bottom line when the Centers for Medicare and Medicaid Services (CMS)begins rolling out initiatives that will reimburse hospitals for the value of the services they provide, in addition to volume. Start now to learn about the new reimbursement initiatives and work with quality staff and physicians to determine what issues need to be addressed. Take a proactive approach to discharges. Ensure patients understand their treatment plans and that there is a smooth transition to the next level of care. Hospitals with excess readmissions for heart failure, pneumonia, and acute myocardial infarction (AMI) will receive reduced reimbursement. Medicare will start tracking spending per-beneficiary for the entire episode of care, beginning three days before admission through 30 days after discharge. PMID- 22066339 TI - Reimbursement changes are on the way. PMID- 22066340 TI - Will you be ready for ICD-10 conversion? AB - In less than two years, the United States will convert to ICD-10, which will result in major changes in coding requirements. Much more detailed documentation will be needed for the coders to do their job correctly. Every department in the hospital that uses data will be affected. Case management software must be adjusted to accommodate the expanded fields. Case managers don't need extensive training on the new codes, but they do need to be aware of the documentation requirements. PMID- 22066341 TI - Handling the transition from staff nurse to case manager. PMID- 22066342 TI - The 9 phases of CM transition. PMID- 22066343 TI - Successful initiative cuts readmissions. AB - Bassett Medical Center's multidisciplinary readmission reduction program resulted in a 70% drop in readmissions for high-risk diagnoses at the Cooperstown, NY, facility. Case managers assess all patients for risk of readmission and alert the team when patients are at high risk. Staff members use the teach-back method and have simplified discharge instructions. Case managers and nurses try to identify barriers to follow-up care while the patient is in the hospital. A patient services coordinator calls at-risk patients after discharge. PMID- 22066344 TI - Literacy screen of parents helps cut costs. PMID- 22066345 TI - [In vitro combination effects of doripenem with aminoglycoside or ciprofloxacin against Pseudomonas aeruginosa]. AB - This study evaluated the in vitro activity of combinations of doripenem (DRPM) with aminoglycosides (tobramycin or amikacin) or fluoroquinolone (ciprofloxacin) against 92 isolates of Pseudomonas aeruginosa from 16 clinical facilities in 2004 in Japan. We also tested combination effect of other carbapenems (imipenem (IPM), meropenem, biapenem) with aminoglycosides or fluoroquinolone by checkerboard dilution methods. DRPM showed synergistic or additive effects with the aminoglycosides or the fluoroquinolone against 90% of the isolates. The combination of DRPM and aminoglycosides showed the strongest synergistic effects against IPM-intermediate resistant and IPM resistant strains among the tested combinations. These results suggested that combination of DRPM with aminoglycosides would be useful for the treatment of infections caused by P aeruginosa including IPM-resistant strains. PMID- 22066346 TI - [Clinical study of levofloxacin 500 mg qd in the treatment of cervicitis and intrauterine infections caused by Chlamydia trachomatis]. AB - The clinical efficacy and safety of levofloxacin (LVFX) 500mg qd were evaluated in female patients with cervicitis with Chlamydia trachomatis and intrauterine infections. LVFX was administered orally at 500 mg qd for 7 days. Bacteriological efficacy was 94.4% (17/18) and clinical efficacy was 100% (16/16) at 14 to 21 days after the end of treatment in cervicitis. On the other hand, bacteriological efficacy and clinical efficacy at the end of treatment in intrauterine infections were 68.8% (11/16) and 94.7% (18/19), respectively. For safety, adverse drug reactions occurred in 9 of 43 patients (20.9%), i.e., increased y-GTP in 2 patients, glucose urine present in 2, and each of all other adverse reactions occurred in 1. All adverse drug reactions observed were either mild or moderate. Results suggested that LVFX 500 mg qd was effective and safe in the treatment of cervicitis with Chlamydia trachomatis and intrauterine infections. PMID- 22066347 TI - [Influence of inoculum size on MICs for methicillin-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus]. AB - Using 49 clinical methicillin-susceptible Staphylococcus aureus isolates (MSSA) and 54 clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, we examined the change of MIC using five different inocula (2.5-4 x 10(2) cfu/spot 2.5-4 x 10(6) cfu/spot). We found the big change of the MIC with the increase of the inoculum size in ampicillin against MSSA, and the change was small in cefazolin, meropenem, ciprofloxacin. For anti-MRSA antibiotics, we found the small change with the increase of the inoculums size in vancomycin and arbekacin, and the middle change in teicoplanin and linezolid against MSSA and MRSA. The data from this study suggest that in serious and high inocula infections caused by S. aureus, the presence of an inoculum effect should be considered in curing. PMID- 22066348 TI - [Case of meningitis caused by group B Streptococcus treated with high dose of meropenem]. AB - We reported a case of meningitis caused by group B Streptococcus treated with high dose of meropenem (MEPM). A 67-year-old male was suffering from lumbago, fever up, vomiting and convulsion. He had received tumor resection of spinal cord at 40 years old. At the first consultation to our hospital, he had felt strong neck stiffness with Glasgow Coma Scale 5 (El, V1, M3), and his body temperature was 37.0 degrees C. His laboratory findings were as follows; white blood cell count 14600/microL, C-reactive protein 4.39mg/dL, and marked elevation of the cell count in the cerebrospinal fluid. We had administered high dose of meropenem, 6 g/day, and also vancomycin (VCM) on therapeutic drug monitoring. Since his clinical symptoms and laboratory findings had not shown adequate response after 4 days later, we had changed VCM to linezolid 1200 mg/day, and had also continued MEPM, which had resulted in prompt resolution of the clinical symptoms and laboratory findings. Microbiological examination for cerebrospinal fluid has yielded a growth of serotype III group B Streptococcus (Streptococcus agalactiae). Since there have been few data on 6 g/day MEPM against meningitis in spite of recommendation in several guidelines, further studies would be necessary including pharmacokinetic-pharmacodynamic analysis. PMID- 22066349 TI - [Drug resistance of Pseudomonas aeruginosa in four community hospitals: influence of antimicrobial use density]. AB - We investigated the relation between hospital antimirobial use density (AUD) and minimum inhibitory concentrations (MIC) for Pseudomonas aeruginosa in four community hospitals. Subjects were a total of 476 strains isolated from urine, sputum, and pus during a total of seven years since 2002, for which 50- and 90 percentile MICs were analyzed. Hospitals A, B, and C moved in 2000, 2005, and 2009, respectively, but MIC50 and MIC90 were stable. MIC values showed significance in five drugs, in which Hospital B showed maximal values in five and Hospital D showed minimal values in four drugs. AUD values were different in nine drugs, Hospital B showing the highest data in meropenem, flomoxef, and sulbactam/cefoperazone while Hospital D having the lowest data in meropenem, ceftazidime, cefotaxime, and sulbactam/cefoperazone. Thus MIC for P aeruginosa may show resistance in the presence of high AUD with wide antimicrobial spectrum. PMID- 22066350 TI - Bridging the gap from innovation to implementation: proceedings from the 4th Florida Valve Symposium. PMID- 22066351 TI - Quantitative echocardiographic assessment of native mitral regurgitation: two- and three-dimensional techniques. AB - Chronic mitral regurgitation (MR) is a common valvular lesion. During recent years, it has become increasingly evident that moderate to severe MR, even in the absence of left ventricular dilatation and dysfunction, may have adverse prognostic consequences. Thus, the accurate quantification of MR, using echocardiography, is vitally important in clinical medicine. Because of the mitral valve's structural complexity, MR is often difficult to define, especially with two-dimensional (2D) imaging methods. Both qualitative and quantitative approaches to the quantification of MR are widely used. Color Doppler imaging allows measurement of the regurgitant jet area and vena contracta (VC) width; these two qualitative methods are simple to apply in daily practice but often are inaccurate, especially in patients with eccentric MR. 2D quantitative methods include the calculation of regurgitant fraction, regurgitant volume, and proximal isovelocity surface area. While these parameters are well-established indicators of MR severity, they require tailored image acquisition and additional calculations; moreover, their accuracy may be compromised in the setting of eccentric MR or aortic insufficiency. With three-dimensional (3D) echocardiography, many of the geometric assumptions necessary with 2D imaging are obviated. A realistic depiction of the VC, which often is non-circular, and of the anatomic regurgitant orifice area, which usually is non-planar, becomes possible with 3D zoom-mode imaging. Ongoing efforts to characterize MR in asymptomatic or minimally symptomatic patients include investigations into stress echocardiography and strain rate imaging. The distinct geometry of the mitral valve, and the various mechanisms of MR, will continue to challenge cardiac research teams during the coming years. PMID- 22066352 TI - Past, present, and future of minimally invasive mitral valve surgery. AB - Minimally invasive mitral valve surgery (mini-MVS) has evolved into a safe and efficient surgical option for many patients. The overall complication rate is reduced, patient satisfaction increased, and hospital costs are lower with this approach, while providing safe and durable surgery. The repair/replacement of mitral valves via a minimally invasive technique represents a significant recent paradigm shift in cardiac surgery. The rapid development and refinement of minimally invasive valve surgery has enabled the repair of complex valves and, most importantly, has yielded similar results to those provided by standard surgical approaches. PMID- 22066353 TI - Transcatheter aortic valve implantation: complications and management. AB - Transcatheter aortic valve implantation (TAVI) is an emerging and promising modality to treat severe aortic stenosis in a select group of patients who are poor surgical candidates. Despite the lesser degree of invasiveness of TAVI compared to open aortic valve replacement (AVR), TAVI is associated with a significant potential for serious life-threatening complications, both intraoperatively and postoperatively. These include vascular injuries, stroke, structural injury to the aorta and the heart and its valves, aortic root or annulus injury, conduction tissue injury, paravalvular leak, valve malposition, coronary complications such as obstruction or ischemia, pericardial effusion and tamponade, and procedural cardiac depression requiring immediate cardiopulmonary bypass for resuscitation. The prevention, detection, and treatment of these complications demands a skill set requiring the services of a cardiovascular surgeon with endovascular skills, an interventional cardiologist, a cardiac perfusion team, and cardiac anesthesia. Therefore, the optimal care of TAVI patients requires a multidisciplinary approach involving these services. The range of serious complications associated with TAVI, and the management strategies utilized in their treatment, are discussed. PMID- 22066354 TI - A low-volume tester for the thrombogenic potential of mechanical heart valve prostheses. AB - BACKGROUND AND AIM OF THE STUDY: During the development of a mechanical heart valve prosthesis, many studies are conducted to guarantee its correct function. Currently, investigations into the thrombogenic potential of a valve after its replacement are conducted with expensive and time-consuming chronic animal trials. Hence, the study aim was to develop and test an alternative system to resolve such thrombogenic issues. METHODS: The Thrombosis Tester of the Helmholtz Institute Aachen (THIA II) has a reasonably small priming volume (220-270 ml) that allows analysis of the thrombogenic potential of two valves, using one human blood bottle. RESULTS: Hydrodynamic evaluation demonstrated an absolutely stable physiological pressure and flow progression at the aortic and pulmonary positions. A sinus geometry of the human aortic root is implemented downstream of the valve in order to guarantee physiological leaflet motion. The tester remained absolutely thrombus-free during several tests carried out with minimally anticoagulated porcine blood, while the valves showed reproducible thrombus formation in reasonable locations. Tests with fully heparinized porcine blood showed that a soft silicon fixture for the valve could reduce hemolysis in the THIA II. CONCLUSION: This in-vitro test protocol can enable the optimization of a valve design during the early stages of its research and development. The system can provide a unique and suitable supplement to animal trials for testing thrombogenic performance, under constant and reproducible boundary conditions, including considerable physiological and pathological circumstances such as the influence of valve position (aortic, pulmonic), and a comparison of different valve types. PMID- 22066355 TI - Results of the first randomized French study evaluating self-testing of the International Normalized Ratio. AB - BACKGROUND AND AIM OF THE STUDY: In this single-center French study, the conventional management of patients receiving vitamin K antagonists (VKAs) was compared with an International Normalized Ratio (INR) self-testing program. The aim was to determine the reliability of self-testing devices, and to estimate the variability of the self-measured INR within the therapeutic and target range. METHODS: A total of 206 patients who had undergone valve replacement with a mechanical prosthesis, with or without myocardial revascularization, between May 2004 and September 2007 was randomized into two groups. Group 1 patients (n = 103) underwent INR monitoring at a laboratory, while Group 2 patients (n = 103) underwent self-testing INR using either the CoaguChek (Roche) (Group 2A; n = 55) or INRatio (Hemosense) (Group 2B; n = 48) system. Patients in Group 1 underwent at least once-monthly INR measurement, while those in Group 2 carried out once weekly self-testing, and also underwent once-monthly INR measurement at the laboratory. The large majority of patients (97.9%) were treated with fluindione. RESULTS: The mean follow up period was 49.0 +/- 10.3 weeks. Self-testing was reliable, with a correlation coefficient between device- and laboratory-measured INRs of 0.80 [CI: 0.78, 0.82] (p < 0.0001). The proportion of time spent within the INR target range was significantly higher for Group 2 (61.5 +/- 19.3% versus 55.5 +/- 19.9%; p < 0.05), while the absolute mean deviation of INR from the target range was higher in Group 1 (60.1 +/- 70.2% versus 47.4 +/- 51.5%). Adverse events were reported by seven patients in Group 1, but by no patients in Group 2 (p < 0.01). CONCLUSION: INR self-testing devices are reliable and beneficial. Moreover, INR self-monitoring allows an enhanced stability within a target range, and also helps to prevent serious postoperative complications. PMID- 22066356 TI - Successful thrombolysis of late, non-obstructive mitral bioprosthetic valve thrombosis: case report and review of the literature. AB - Bioprosthetic valve thrombosis is an unexpected complication which has no guidelines for its management. A 70-year-old female presented 10 days after a stroke, three years after having undergone mitral bioprosthetic valve implantation. Both, transthoracic echocardiography and transesophageal echocardiography (TEE) revealed a large mobile, non-obstructive mass attached to the atrial side of the sewing ring of the bioprosthesis. The administration of low-molecular-weight heparin and aspirin resulted only in a reduction of thrombus size, whereas a slow streptokinase infusion resulted in complete disappearance of the thrombus after 16 h. A review of the literature shows that late non obstructive bioprosthetic valve thrombosis, as diagnosed with TEE, is a rare condition that can be successfully treated either by anticoagulant or thrombolytic therapy. Late bioprosthetic valve thrombosis should be considered as a cause of prosthetic valve dysfunction, and long-term preventive anticoagulant treatment of high-risk patients is warranted. Slow thrombolytic therapy is safe and successful, even for large non-obstructive bioprosthetic thrombi, if there are no contraindications. PMID- 22066357 TI - Left ventricular remodeling, hemodynamics and early clinical outcomes after aortic valve replacement with the Pericarbon Freedom stentless bioprosthesis: results from the Italian Prospective Multicenter Trial. AB - BACKGROUND AND AIM OF THE STUDY: The aims of this multicenter prospective observational trial were to evaluate: (i) the left ventricular remodeling, hemodynamics and early clinical outcomes of patients undergoing aortic valve replacement (AVR) with the Pericarbon Freedom (PF) stentless bioprosthesis; and (ii) the impact of the two suture techniques--continuous and interrupted--on the hemodynamic performance of the bioprosthesis. METHODS: Between November 2001 and April 2004, a total of 226 patients (131 females, 95 males; mean age 73.2 +/- 8.8 years) underwent AVR with the PF valve (Sorin Group, Saluggia, Italy) at eight Italian cardiac surgery centers. Associated surgery was performed in 73 patients (32%); of these operations, 54 were coronary artery bypass grafting. A continuous suture technique was used in 132 patients (58%), and an interrupted-suture in 90 (40%). The suture technique was not available for four patients. All patients underwent clinical and echocardiographic evaluation immediately before surgery, and at one, six, and 12 months thereafter. The median follow up was 380 days (Q1: 363 days; Q3: 410 days), and the total cumulative follow up 236.9 patient-years (pt-yr). RESULTS: The overall 30-day mortality was 3.5% (n = 8). Late deaths occurred in 10 patients (4%/pt-yr), of which three were valve-related (1%/pt-yr). The overall and valve-related survivals at one year were 92 +/- 2% and 98 +/- 1%, respectively. Freedom from structural valve deterioration, endocarditis, reoperation and thromboembolic events was 100%, 93 +/- 1%, 98 +/- 1% and 99 +/- 1% at one year, respectively. The peak and mean transprosthetic gradients at one year were: 19.7 +/- 12.27 and 8.7 +/- 6.0 mmHg, respectively. After 12 months, significant reductions (compared to preoperative) were observed in the left ventricular mass (148.5 +/- 48.8 versus 194.4 +/- 54.6 g/m2; p < 0.001) and mean wall thickness (1.08 +/- 0.19 versus 1.32 +/- 0.23 cm; p < 0.001). The continuous suture technique showed a trend towards lower postoperative gradients than did the interrupted-suture technique. CONCLUSION: The data obtained indicated that the PF bioprosthesis provided excellent results in terms of left ventricular mass regression, hemodynamics, and early clinical outcome. Although a trend towards a better hemodynamic performance of the continuous-suture technique was observed, this aspect requires further evaluation. PMID- 22066358 TI - The value of intraoperative transesophageal echocardiography in patients undergoing aortic valve replacement. AB - BACKGROUND AND AIM OF THE STUDY: While the role of intraoperative transesophageal echocardiography (IOTEE) in valve repair surgery is well documented, its value in patients undergoing valve replacement is debatable. The study aim was to assess the impact of IOTEE on the management of a large cohort of patients referred for aortic valve replacement (AVR). METHODS: The departmental echocardiography database for patients undergoing AVR with IOTEE between April 1999 and September 2006 at the authors' institution was reviewed. Patients with a diagnosis of infective endocarditis, aortic dissection, or those in whom a composite graft was implanted, were excluded from the study. RESULTS: The study group included 604 patients (319 males, 285 females; mean age 70 +/- 11 years) who underwent AVR for either predominant aortic stenosis (n = 520; 86.1%) or aortic regurgitation (n = 84; 13.9%). Pre-pump IOTEE was performed in 440 patients (72.8%), and post-pump IOTEE in 586 (97.0%). Overall major preoperative findings influencing the operative plan were found in 106 of the 440 patients (24.1%); decisions regarding the mitral valve were the most frequent. The post-pump study revealed unexpected findings requiring a second pump run in 20 patients (3.4%), of whom nine cases (1.5%) applied to the replaced aortic prostheses (paravalvular leak in five patients, coronary obstruction by an aortic bioprosthesis in two, and detection and closure of a pseudoaneurysm in the mitral-aortic fibrosa and incompetent bioprosthesis in one patient each). Eleven patients (1.8%) required a second pump run because of failed mitral/tricuspid repair or hemodynamic compromise. CONCLUSION: The main use of a routine application of IOTEE among patients undergoing AVR was to detect additional lesions preoperatively, and technical failures postoperatively. PMID- 22066359 TI - Statin treatment and gene expression of anti-atherogenic factor C-type natriuretic peptide system in stenotic aortic valves. AB - AIMS: Aortic valve calcification is an actively regulated process with endothelial dysfunction displaying hallmarks of atherosclerosis. C-type natriuretic peptide (CNP) system has been reported to have a role in the pathogenesis of vascular atherosclerosis and to be distinctly downregulated in aortic valve stenosis (AS). Here we studied gene expressions of CNP and is target receptor natriuretic peptide receptor type B (NPR-B) in human aortic valves. Furthermore, we compared gene expression of CNP system in patients with HMG coenzyme-A reductase (statin) treatment to non-statin-treated patients in AS group. METHODS AND RESULTS: With the study population of 108 patients, we characterized expression of CNP and NPR-B in human aortic valves and compared normal control valves (n = 12) with valves obtained from patients with aortic regurgitation (AR, n = 16), AR with fibrosis (AR+fibr., n = 19) and AS (n = 61). By reverse transcription-polymerase chain reaction (RT-PCR), CNP mRNA levels were 89% lower (p = 0.022) in stenotic valves, when compared to AR group. Moreover, the mRNA levels of NPR-B, the target receptor of CNP, were 62% lower (p < 0.001) in stenotic valves when compared to control group and 54% lower (p = 0.002) in stenotic valves, when compared to AR group. There was no statistical significant difference in CNP and NPR-B levels in AS group when the statin-treated patients were compared to untreated patients. CONCLUSIONS: These results show for the first time that the gene expression of anti-atherogenic CNP system did not differ between statin-treated and non-statin-treated patients in AS. The research data supports the results of clinical trials with the same drug class. PMID- 22066360 TI - Echocardiographic patterns of incomplete Shone's syndrome in adults. AB - BACKGROUND AND AIM OF THE STUDY: Whilst several cases of complete Shone's complex have been reported in children, the incomplete form--characterized by two or three components--has rarely been described in adults. Because of the wide spectrum of severity of each pattern, the correct diagnosis may be challenging. Moreover, as the hemodynamic interdependence between defects is thought to be a major determinant of clinical outcome and long-term follow up, it is crucial to consider the lesions as part of the same Shone's syndrome. METHODS: Between May 2005 and December 2009, six male patients (mean age 38 +/- 8 years) were referred to the authors' institute with progressive worsening of heart failure symptoms related to valvular disease. All patients had a clinical history of surgery for coarctation of the aorta (CoA), and all but one had a bicuspid aortic valve. Standard transthoracic and transesophageal echocardiographies were performed in all patients to identify the valvular heart disease responsible for clinical deterioration. RESULTS: Unexpected findings of dysplastic mitral valvular apparatus compatible with parachute deformity of the mitral valve (PMV) or 'PMV like' morphology were disclosed in all patients. The association with major anatomic abnormalities (bicuspid aortic valve, subaortic ridge, and previous CoA surgical repair) was highly suggestive of adult incomplete Shone's syndrome. CONCLUSION: The findings of the present case series emphasized the need for a greater awareness regarding the rare incomplete Shone's syndrome in adulthood, as it occurs far more frequently than might be expected following a random diagnosis. The findings also highlight the additional value of a carefully performed step-by-step echocardiographic study to support the clinical decision making in this array of left heart anomalies. PMID- 22066361 TI - Incremental prognostic value of echocardiography in patients with prior mitral valve surgery. AB - BACKGROUND AND AIM OF THE STUDY: Patients with prior mitral valve surgery are at increased risk for events late after surgery. The study aim was to investigate the value of assessing clinical variables, and left and right heart anatomy and function, to predict outcome in these patients. METHODS: Two-dimensional echocardiography, Doppler echocardiography and tissue Doppler imaging (TDI) were performed in 84 patients at a mean of 7.3 +/- 7.1 years after mitral valve surgery. The left ventricular ejection fraction (LVEF) was 50 +/- 15%, and 30% of patients were in NYHA class III/IV (congestive heart failure; CHF). Follow up was obtained for events that included repeat mitral or tricuspid valve surgery, and death. RESULTS: During a follow up period of 4.3 +/- 2.0 years, 28 patients suffered events, the univariate clinical predictors of which were NYHA class, calcium antagonist therapy, hyperlipidemia, and tobacco smoking. Left heart predictors included the mean mitral valve gradient (MMVG), left atrial volume index, and lateral wall TDI systolic velocity. Right heart predictors were atrial and right ventricular (RV) dimensions, RV systolic pressure, tricuspid regurgitation (TR) severity, RV free wall TDI E-velocity and E/e' ratio. Multivariate analysis showed that NYHA class (p = 0.02; RR 1.8 (1.1-2.9)), MMVG (p < 0.001; RR 1.16 (1.08-1.24)) and RV dimensions (p = 0.001; RR = 3.2 (1.7 6.2)) were independent predictors of events. A step-wise analysis of independent predictors showed that MMVG added an incremental value to NYHA class (p = 0.003), while RV size added additional value (p = 0.007) to the combination of NYHA class and MMVG. CONCLUSION: Echocardiographic assessments of the left and right heart can add significant prognostic value to the clinical assessment of patients after mitral valve surgery. PMID- 22066362 TI - Functional tricuspid valve regurgitation in adults with congenital heart disease: an emerging problem. AB - BACKGROUND AND AIM OF THE STUDY: At present, limited data are available regarding functional tricuspid regurgitation (TR) in adults with congenital heart disease (ACHD). Functional TR is the consequence of right ventricular (RV) dilation or dysfunction that, in these patients, is typically associated with chronic RV volume overloading. The study aim was to resolve this problem by evaluating results obtained from patients after surgical treatment of ACHD. METHODS: A total of 65 patients (mean age 46 years) with ACHD underwent an operation to correct functional TR during elective cardiac surgery between January 2000 and December 2008 at the authors' institution. The preoperative median NYHA functional class was 3, and the median TR grade was 3. Surgical treatment of the primary cardiac lesion included atrial septal defect (ASD) closure in 40 patients and pulmonary valve implantation in 25. Functional TR was treated by annuloplasty (n = 48), rigid tricuspid valve ring (n = 14), or tricuspid valve replacement (n = 3). RESULTS: There were no in-hospital deaths. The median TR grade at discharge was 0. During a mean follow up period of 63 months (range: 12-96 months) there was one delayed death that was not cardiac-related. Both, the NYHA functional class (p = 0.001) and TR grade (p = 0.001) were significantly improved among survivors. One patient (1.5%) had tricuspid valve replacement at five years after annuloplasty. No significant differences regarding annuloplasty versus rigid tricuspid valve ring were noted during the follow up period. CONCLUSION: Functional TR is an emerging, though as yet still underestimated, problem in ACHD. It is a consequence of RV dilation/dysfunction that, in these patients, is typically related to chronic RV volume overloading. Surgery should be considered to resolve this problem, and can be performed at low risk and with good mid-term results. PMID- 22066363 TI - Cryopreserved homograft in the Ross procedure: outcomes and prognostic factors. AB - BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the dynamics and risk factors related to cryopreserved homografts implanted to reconstruct the right ventricular outflow tract (RVOT) during the Ross procedure. METHODS: A retrospective study, conducted between 1993 and 2009, included 107 consecutive patients who underwent a Ross procedure with implantation of a homograft (102 pulmonary, five aortic). The median patient age at implant was 18.8 years (range: 2 months - 67 years). The main cardiac defects were congenital aortic stenosis (n = 44), congenital aortic regurgitation (n = 20), and combined (n = 23) and acquired (n = 20) aortic regurgitation. The study endpoints were homograft stenosis (peak gradient > or = 20 mmHg), regurgitation (grade > or = moderate), homograft dysfunction (stenosis > or = 50 mmHg or regurgitation > or = moderate), homograft explant, and failure (explant or balloon dilation). The mean follow up was 5.7 +/- 0.4 years. The statistical analysis was conducted using univariate and multivariate Cox regression tests. RESULTS: The overall patient survival was 97% at 18 years. Homograft stenosis occurred in 54% of patients, regurgitation in 18%, dysfunction in 27%, explant in 5%, and failure in 6%. Freedom from homograft dysfunction was 75% and 55% at five and 10 years, respectively, while freedom from homograft failure was 99% and 84% at five and 10 years, respectively. The main multivariate risk factors for dysfunction were: homograft diameter < 22 mm (OR: 11, p = 0.019), aortic homograft (OR: 18, p = 0.019) and preoperative right ventricle/left ventricle pressure ratio > 0.4 (OR: 5, p = 0.018). Univariate risk factors for failure were: homograft diameter < 22 mm (p = 0.006), donor age < 30 years (p = 0.03), cold ischemia time < 2 days (p = 0.04), and decontamination time < 12 h (p = 0.01). CONCLUSION: In the Ross procedure, the cryopreserved homograft represents an excellent means to reconstruct the RVOT, with a good long term longevity. Almost 85% of patients did not require any surgery or percutaneous intervention at 10 years after implantation. The homograft long-term durability depends on both homograft-related and patient-related factors. Pulmonary homografts, with a diameter > 22 mm, a donor age > 30 years, and a cold ischemia time > 2 days are to be preferred. PMID- 22066364 TI - Antibiotic pretreatment of heart valve prostheses to prevent early prosthetic valve endocarditis. AB - BACKGROUND AND AIM OF THE STUDY: Prosthetic valve endocarditis (PVE), a rare but major complication after heart valve replacement surgery, has potentially catastrophic consequences despite maximal treatment. Thus, preventive measures are essential. The study aim was to investigate the effect of pretreating heart valve prostheses with the antibiotics baneomycin and daptomycin, with and without surgical sealant fibrin glue as a drug-releasing substance. The biocompatibility of baneocin and daptomycin was also investigated. METHODS: Samples of polyethylene terephthalate (PTE), as used for the sewing cuffs of prosthetic heart valves, were tested; untreated samples served as controls. All samples were contaminated with Staphylococcus epidermidis, and colony-forming units (CFUs) then counted. Cytotoxicity tests were performed using the MTT-assay to evaluate the effects of baneomycin and daptomycin on cell proliferation and wound healing. RESULTS: Untreated and fibrin glue-coated samples were directly infected with a bacterial count of 2.82 +/- 0.63 x 10(5) CFU/ml and 2.80 +/- 1.07 x 10(5) CFU/ml, on average. Baneocin-impregnated samples were sterile for 1.9 +/- 0.38 days, with a subsequent bacterial count of 2.26 +/- 0.6 x 10(5) CFU/ml, while daptomycin impregnated samples were sterile for 2.9 +/- 0.38 days, with a subsequent bacterial count of 1.81 +/- 0.53 x 10(5) CFU/ml. Samples coated with a fibrin glue-baneocin mixture were sterile for 3.14 +/- 0.38 days, after which the bacterial count was 0.74 +/- 0.47 x 10(5) CFU/ml. After coating with a fibrin glue-daptomycin mixture, samples were sterile for 7.0 +/- 0.58 days, and the bacterial count was 0.70 +/- 0.56 x 10(5) CFU/ml. CONCLUSION: In this in-vitro study, the pretreatment of prosthetic heart valves with antibiotics reduced the risk of bacterial adhesion and consequent infection. The combination of antibiotics with fibrin glue prolonged this preventive effect, with baneocin demonstrating a better biocompatibility than daptomycin. On the basis of its antibacterial efficacy, daptomycin appears to be a more suitable antibiotic to prevent early PVE with Gram-positive bacteria. The soaking of prosthetic heart valves in antibiotic solutions prior to implantation, in combination with fibrin glue in cases of suspected endocarditis, can prevent the development of early PVE. This preventive strategy should be investigated for use as a standard procedure in clinical practice. PMID- 22066365 TI - Polyester mesh: an alternative material for reinforcing the pulmonary autograft root. AB - Today, it is widely accepted that the pulmonary autograft should be reinforced when used as a root in the Ross operation. Various techniques using a vascular conduit have been reported. Herein is described an alternative technique, using a polyester mesh, that was applied in a 15-year-old boy with recurrent congenital stenosis. The advantages of using a mesh rather than a solid vascular prosthesis are discussed. PMID- 22066366 TI - Designing a stentless valve conduit for use in a biological Bentall procedure. AB - Various modifications of the Bentall procedure have been described using mechanical valve conduits. A further modification, using a bioprosthetic valve, has grown in popularity as this prevents the need for lifelong anticoagulation. Additional innovation using a stentless bioprosthetic valve has the theoretical advantages of allowing for a larger bioprosthesis and an improved durability. The technical aspects involved in designing a stentless valve conduit for use in a biological Bentall procedure are described. PMID- 22066367 TI - Alternative valve-in-root concepts for redo procedures. AB - Since aortic root reoperations are challenging procedures, alternative lower-risk procedures should be considered in certain cases. Herein are presented two different approaches to high-risk root reoperations. The first patient, a 59-year old male who had undergone root replacement 11 years previously with an Edwards Prima stentless valve, presented with severe aortic regurgitation and a heavily calcified aortic root. An open implantation of an Edwards Sapien valve was performed via an aortotomy distal to the calcified aortic root. The second patient, a 60-year-old female, underwent transapical implantation of an Edwards Sapien transcatheter valve for stenosis of the aortic valve in an aortic homograft implanted 11 years previously. The long-term durability of these implants has yet to be evaluated. PMID- 22066368 TI - Pneumococcal endocarditis with extremely rapid valve destruction in a splenectomized host. AB - A 45-year-old patient presented with fever and pneumococcal bacteremia. Transthoracic echocardiography, performed on the second day of admission, was unremarkable; however, repeat imaging performed only 60 h later showed destruction of posterior mitral valve leaflet with severe mitral regurgitation, and large, newly developed vegetations appearing on the mitral valve and the left ventricular outflow tract (LVOT). The patient underwent successful mitral valve replacement, with debridement of the LVOT vegetation. The findings of the present case illustrate the highly aggressive nature of pneumococcal endocarditis that is uncommonly encountered in the current, penicillin, era. PMID- 22066369 TI - Myxoma on a mechanical mitral valve annulus. AB - To date, myxoma on a mechanical valve annulus has not been reported. The case is reported of a 74-year-old woman who was admitted to hospital following the identification of an intracardiac tumor mass. Six years previously, the patient had received a mechanical valve implanted in the mitral position. Transesophageal echocardiography revealed a mobile hypoechogenic tumorous mass attached to the anterior annulus of the prosthesis. The tumor was successfully treated by surgical excision, and a diagnosis of myxoma was confirmed both clinically and pathologically. PMID- 22066370 TI - Successful balloon mitral valvotomy in rheumatic mitral stenosis with Ebstein's anomaly. AB - The association of Ebstein's anomaly of tricuspid valve with rheumatic mitral stenosis is extremely rare. The case is presented of a young female who had been admitted with progressive dyspnea secondary to severe rheumatic mitral stenosis with moderate pulmonary hypertension, along with Ebstein's anomaly of tricuspid valve. The patient underwent successful balloon mitral valvotomy, using the Inoue technique, with a marked improvement in her symptoms. PMID- 22066371 TI - Unusual complication after aortic valve replacement with the Freedom Solo stentless bioprosthesis. AB - The case is presented of an unusual complication after aortic valve replacement with a Freedom Solo bioprosthesis. Excision of the aortic valve created a discontinuity of the aortic annulus that was missed intraoperatively and left uncorrected after supra-annular placement of the bioprosthesis; this created a pseudoaneurysm with direct communication to the pericardial cavity. When implanting the Freedom Solo bioprosthesis, care must be taken to exclude the presence of any aortic annular discontinuity. Implantation of the Freedom Solo bioprosthesis is not precluded by this possible complication, provided that any annular disruption is promptly recognized and adequately closed before placement of the supra-annular sutures. PMID- 22066372 TI - A valid option for complex reoperations on the ascending aorta. PMID- 22066373 TI - [The three lives of "Doctor Pack"]. PMID- 22066374 TI - [The dependence debate]. PMID- 22066375 TI - [The worrying associations of the governmental report of social and financial dependence]. PMID- 22066376 TI - [Respect towards people with alzheimer's disease]. AB - The quality of life and the dignity of the residents with Alzheimer dementia (AD) passes by the respect that is demonstrated to them. A study conducted in Quebec (Canada) seeks to define the concrete manifestations of this concept often put forward but rarely made explicit. Elements of answer are found in the attitude of the caregivers as well as in the environment and the activities proposed to the elderly. PMID- 22066378 TI - [The administrator of Ehpad retirement home]. PMID- 22066377 TI - [Helping the caregivers of alzheimer patients]. PMID- 22066379 TI - [Depression in the elderly. Towards a common approach]. PMID- 22066380 TI - [The psychological dynamics of depression in the elderly]. AB - Depression in the elderly can be difficult to detect. Examining the normal depressive and pathological affect can help to determine the meaning of the depression. Likewise, the effects of psychological dynamics on the clinical profile and treatments clarify our approaches and our practices. PMID- 22066381 TI - [Detecting the signs of suicide in the elderly]. AB - The assessment of the suicide risk in elderly people is carried out in accordance with specific criteria. Difficulties are linked to the person's representations and attitudes towards death. There are indications and early signs which must be recognised in order to prevent suicide attempts. PMID- 22066382 TI - [Suicide in elderly people, an underestimated public health phenomenon]. AB - Although adolescent suicide is more widely spoken about, the suicide rate is actually higher among elderly people. Preventing elderly people from attempting suicide and raising awareness among family and friends are priorities for our nursing practices. PMID- 22066383 TI - [The elderly and death]. AB - The approach of death is the source of an ambivalence for the elderly. Between anguish and weariness, some do however succeed in attaining some sort of serenity. Talking about death, which is a taboo in our modern societies, allows a person at the end of her life to exorcise her one fears but may hurt the relatives who are not well prepared. The understanding of each one of these aspects is crucial when dealing with the medical care of the elderly. PMID- 22066384 TI - [Pain as a symptom of depression in the elderly]. AB - Depression in elderly people can manifest itself in an unexpected manner. In the case of Mrs Y., the physical pain masked psychological suffering linked to anxiety about death and abandonment. The care provided by a multi-disciplinary team, based on a joint thinking process, enabled her to emerge from this impasse and benefit from a coherent care project. PMID- 22066385 TI - [Home nursing care for depressed elderly people]. AB - The freelance nurse must be adaptable and reactive in order to meet the needs of a depressed or suicidal elderly person. In addition to her own particular relationship with the patient, the nurse must activate a network of other professionals who can carry out home visits. PMID- 22066386 TI - [Depression in the elderly. Bibliography]. PMID- 22066387 TI - [Diabetic foot in the elderly]. PMID- 22066388 TI - [Long-term care]. PMID- 22066389 TI - [Effects of covering on growth potential and chlorophyll content of hardwood cutting of Lycium barbarum]. AB - OBJECTIVE: To study the effect of plastic film covering, straw covering, plastic film covering in greenhouse and no-covering cutting on growth and Chlorophyll content of Lycium barbarum hardwood cutting seedlings. METHODS: Single factor randomized block design method was used in this research. RESULTS: The effect of different covering treatments on germination rate, seedling rate and growth potential were all plastic film covering in greenhouse > plastic film covering > straw covering > no-covering cutting. Chlorophyll a, Chlorophyll b, Chlorophyll a + b content and Ca/Cb were significantly different with different coverings in different periods. CONCLUSION: The optimal covering on hardwood cutting of Lycium barbarum is plastic film covering in greenhouse. Both plastic film and straw covering are better than no-covering cutting. PMID- 22066390 TI - [Study on the virus-free technology of Pinellia temata]. AB - OBJECTIVE: To solve the degradation of production and quality of Pinellia caused by the virus accumulation, rapid propagation technical of virus-free Pinellia was researched. METHODS: Pinellia leaves,petioles as explants, technology of using high temperature (38 degrees C, 40d) and shoot tip culture producing virus-free Pinellia was explored. RESULTS: The results showed that leaves without virus spots was about 88.9% when explants were culture for 40d at high temperature (38 degrees C). 1.0 mg/L 6-BA and 0.1 mg/L NAA could induce seedling from shoot tip,seedling rate is up to 91.4%; MS added 0.5 mg/L 6-BA and 0.1 mg/L NAA was conducive to growth of the plantlets; added 0.5 mg/L KT and 0.5 mg/L NAA was in favor of inducing root and promoting root growth, the survival rate of the transplanting seedling could reach 89.5%. CONCLUSION: A reliable system of virus free Pinellia propagation is established. PMID- 22066391 TI - [Inhibitory effects of Gecko alcohol extract on human esophageal squamous carcinoma cell line EC-109 proliferation and associated mechanism]. AB - OBJECTIVE: To explore the proliferation inhibition effects of Gecko alcohol extract (GAE) on human esophageal squamous carcinoma cell line EC-109 and its mechanism. METHODS: The inhibitory effects of GAE on proliferation of EC-109 cells were measured by MTT. Nucleolus change of apoptotic cells was observed by Hoechest33342 fluorescence staining. Apoptosis rate of EC-109 cells was detected by flow cytometry. The expressions of apoptosis protein Caspase-3 and FAS in EC 109 cells were investigated by immunohistochemistry. RESULTS: GAE had the inhibition effects on the proliferation of esophageal carcinoma cell EC-109. The apoptosis rate of EC-109 cell treated with GAE(3.0 mg/mL, 4.0 mg/mL) for 48h was 20.63% and 39.73%, respectively. Compared with control group,the expression of Fas and Caspase-3 was significantly up-regulated in GAE treated group. CONCLUSION: GAE can inhibit the proliferation of esophageal carcinoma EC-109 cells and induce them apoptosis which may be correlated with increasing expression of protein Fas and Caspase-3. PMID- 22066392 TI - [Study on the flavon ingredients of Malus hupehensis]. AB - OBJECTIVE: To investigate the flavon ingnedients of Malus hupehensis, Malus toringoides and Malus hupehensis var. pinyiensis. METHODS: TLC was used for the qualitative identification of Malus hupehensis, Malus toringoides and Malus hupehensis var. pinyiensis. The content of total flavonoids was determined by UV spectrophotometry and the content of phlorizin was determined by HPLC. RESULTS: The TLC spots were clear and well separated. The maximum absorption wavelength of phlorizin was 287 nm. The content of total flavonoids of 6 batches of Malus hupehensis ranged from 19.65 mg/g to 20.97 mg/g, Malus toringoides ranged from 10.71 mg/g to 12.13 mg/g and Malus hupehensis var. pinyiensis. ranged from 3.49 mg/g to 3.67 mg/g. The content of phlorizin of Malus hupehensis was 15.51 mg/g, Malus toringoides was 14.66 mg/g and Malus hupehensis var. pinyiensis was 2.05 mg/g. CONCLUSION: Established method is applicable for the study of flavonoid compositione ingredients. PMID- 22066393 TI - [Study on seed morphology of the section Cruciata Gaudin]. AB - OBJECTIVE: To provide a scientific evidence for the identification of the section Cruciata Gaudin. METHODS: Seed morphology of the section Cruciata Gaudin in different regions from Gansu were studied by means of scanning electronic microscopy (SEM). RESULTS: The seeds of section Cruciata Gaudin had relative conformability in terms of shape,size and ornamentation. But the reticulate cell of Gentiana dahurica was obviously wider than those of other species. CONCLUSION: This study provides some useful information for classification and identification of section Cruciata Gaudin. PMID- 22066394 TI - [Quantitative determination of peimisin and total alkaloids in Fritillaria taipaiensis of different growing stage]. AB - OBJECTIVE: To study the content of peimisine and total alkaloids in Fritllaria taipaiensis of different growing stage. METHODS: High performance liquid chromatography coupled with evaporative light scattering detector was employed, and peimisine was separated and quantified upon an Agilent Extend C18 (250 mm x 4.0 mm, 5 microm), using acetonitrile-water-diethylamine as the mobile phase at the flow rate of 1.0 mL min(-1); UV spectrophotometry was used for the determination of total alkaloids. RESULTS: During from two to three years period, the content of peimisine in F. taipaiensis increased with growing stage, from four to six years, it decreased with growing stage; From two to four years, the content of total alkaloids in F. taipaiensis increased with growing stage, from five to six years, it decreased with growing stage. CONCLUSION: It is suitable to harvest F. taipaienssi of four years growing stage. PMID- 22066395 TI - [Study on the initial processing of Corydalis yanhusuo]. AB - OBJECTIVE: To establish initial processing technology of Corydalis yanhusuo. METHODS: Investigated the effect of the factors such as slice method, dry method, drying temperature on the content of water-extract, ethanol-extract, effective component in Corydalis yanhusuo pieces. Compared the quality with that of the traditional initial processing samples. RESULTS: The best initial process method was: cut fresh Corydalis yanhusuo into 4 - 5 mm thick slices, dry at 70 - 80 degrees C or microwave dry. CONCLUSION: The study provides theoretical base for modifying the initial processing. PMID- 22066396 TI - [Fingerprints of Rosae Rugosae Flos by HPLC]. AB - OBJECTIVE: To establish a HPLC fingerprint of Rosae Rugosae Flos. METHODS: Inertsil ODS-3 (4.6 mm x 250 mm, 5 microm) was used with the mixture of methanol, acetonitrile and 0.06% TFA as mobile phase. The flow rate was 1.0 mL/min, the column temperature was 32degrees C, and the detection wavelength was 254 nm. RESULTS: HPLC fingerprint of 9 main peaks was established preliminarily from 13 samples of Rosae Rugosae Flos which achieved the technical requirements of the fingerprint of traditional Chinese medicine. CONCLUSION: The method is reliable, accurate and can be used for quality comtrol of Rosae Rugosae Flos. PMID- 22066397 TI - [Chemical constituents of Carya cathayensis and their antitumor bioactivity]. AB - OBJECTIVE: To investigate the chemical constituents of Carya cathayensis and their antitumor bioactivity. METHODS: The compounds were isolated by Sephadex LH 20 and silica gel column chromatography. Their structures were identified by physicochemical properties and spectroscopic analysis. Then their cytotoxic activity was studied. RESULTS: Five compounds were elucidated as chrysophanol (1), physcion (2), beta-sitosterol (3), pinostrobin(4), 4,8-dihydroxy-1-tetralone (5). CONCLUSION: Compounds 2 and 5 are isolated from Carya cathayensis for the first time. In the MTT antitumor experiments, the compounds 1,4 and 5 have the cytotoxic activity to KB cell. PMID- 22066398 TI - [Study on the chemical constituents of aerial part of Ligusticum jeholense]. AB - OBJECTIVE: To study the chemical constituents of the aerial part of Ligusticum jeholense. METHODS: The constituents were isolated by sillica gel column chromatography, Sephadex LH-20 column chromatography and their structures were elucidated by spectral analysis. RESULTS: Seven compounds were separated from the EtOH extracts. Their structures were identified as psoralen (1), beta-sitosterol (2), daucosterol (3), kaempferol-3-O-(2",4"-di-E-p-coumaroyl)-alpha-L-rhamnoside (4), kaempferol-3-O-beta-D-galactoside (5), quercetin-3-O-beta-D-galactoside (6), sucrose (7). CONCLUSION: Compounds 1, 4, 5 and 6 are isolated from the genus for the first time. Compounds 2, 3 and 7 are isolated from the aerial part of the plant for the first time. PMID- 22066399 TI - [Study on the chemical constituents of Pithecellobium clypearia]. AB - OBJECTIVE: To study the chemical constituents of Pithecellobium clypearia. METHODS: Silica gel column chromatography and Sephadex LH-20 were used to separate and purify compounds from the EtOAc soluble fraction of Pithecellobium clypearia. 9 compounds were elucidated on the basis of physicochemical properties and spectrascopic analysis. RESULTS: They were identified as beta-Sitosterol (1), tritriacontane (2), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (3), oleanolic acid (4), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (5), alpha-amyrin (6), luteolin (7), ursolic acid (8), luteoloside (9). CONCLUSION: Compounds 3 and 5 are isolated from this plant for the first time. PMID- 22066400 TI - [Isolation of alkaloids from Corydalis saxicola by high-speed counter-current chromatography]. AB - OBJECTIVE: To develop a method for the rapid isolation of alkaloids from the crude extract of Corydalis saxicola. METHODS: High-speed counter-current chromatography (HSCCC) was applied for the separation of alkaloids from Corydalis saxicola, with the biphase solvent systems comprised n-butanol-ethyl acetate water-formic acid (5: 1: 5: 0.01) and n-butanol-ethyl acetate-methanol-water formic acid (5: 5: 1:9:0.05). RESULTS: About 300 mg of crude extract was isolated by HSCCC, yielding 3.6 mg of scoulerine, 9.2 mg of isocorydine, 5.5 mg of dehydrocheilanthifoline, 7.5 mg of dehydrocavidine, 20.4 mg of palmatine and 20.9 mg of berberine, with purities of 71%, 92%, 85%, 76%, 90%, 97%, respectively. CONCLUSION: It is time-saving and simple to isolate alkaloids from Corydalis saxicola by HSCCC with high yields and purities. PMID- 22066401 TI - [Analysis of the chemical constituents of essential oil from Ligustrum quihoui by GC-MS]. AB - OBJECTIVE: [corrected] To study the chemical constituents of essential oil from Ligustrum quihoui. METHODS: Essential oil was extracted by steam distillation (SD). The chemical constituents of essential oil was analyzed by GC-MS. RESULTS: The chemical components in the oil were qualitatively and quantitatively analyzed by GC-MS, 76 components were seperated and 35 components were identified. The main components are n-Hexadecanoic acid (17.28%), (Z, Z, Z)-9, 12, 15 Octadecatrienoic acid, ethyl ester (12.13%), Phytol (5.80%). CONCLUSION: The method is simple, reliable and with good reprodutivity. PMID- 22066402 TI - [Analysis of the constituents of volatile oil from Fructus Auranti Immaturus by GC-MS]. AB - OBJECTIVE: To analysis the constituents of volatile oil from Fructus Auranti Immaturus by GC-MS. METHODS: The volatile oil was extracted by steam distillation, then separated by capillary gas chromatography. The constituents of volatile oil were identified and their amount were determined by normalization method. RESULTS: Nineteen components were identified from Fructus Auranti Immaturus and their amount accounted 95.791% of total volatile oil. The main components were Limonene (68.25%), gamma-Terpinene (13.02%), alpha-Terpinol (3.28%), beta-Cymene (3.09%), beta-Myrcene (2.34%), alpha-Pinene (1.53%), beta Pinene (1.05%). CONCLUSION: The main component of volatile oil from Fructus Auranti is Limonene. PMID- 22066403 TI - [Simulation study of antithrombotic active fraction of Naodesheng by support vector machine]. AB - OBJECTIVE: To screen the antithrombotic active fraction of Naodesheng. METHODS: The collagen and adrenaline-induced thrombosis by tail intravenous injection in mice was used. Based on orthogonal design, the support vector machine model was established for pharmacodynamics prediction of TCM prescriptions. RESULTS: The model established in this study could predict the drug actions of different combinations. CONCLUSION: The pharmacodynamic actions of several formulas are superior to that of the original formula and CD has the best effect. PMID- 22066404 TI - [Effect of Nuanxin Capsule on two rat models with heart failure]. AB - OBJECTIVE: To observe the effects of Nuanxin Capsule (NC) on the rat models of heart failure induced by abdominal aorta constriction and adriamycin. METHODS: Rats were randomly divided into the following groups: model control group, low dose and high-dose, and digoxin group. Meanwhile, the pseudo-operation and NC groups were seperately established. After treatment for 30 days, the heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal rate of increase and decrease in left ventricular pressure (+/- dp/dt), mean peripheral blood pressure (MBP) as well as levels of serum superoxide dismustase (SOD), malondialdeh-vde (MDA), cardiac index and heart size were measured. RESULTS: SBP, LVSP, +/- dp/dt and SOD activity increased,while LVEDP,serum MDA levels decreased in high and low-dose NC groups of two models. The heart rates also decreased, but the difference was insignificant (P>0.05, compared with those of model group). Besides, the heart rate,heart size and cardiac index, as well as serum Ang II levels also decreased. The differences were significant as compared with the digoxin group (P>0.05). The high-dose NC also significatly improved MBP and SOD (P<0.05 and P<0.01). CONCLUSION: Nuanxin Capsule has good therapeutic effects on the rats models of adriamycin and abdominal aorta constriction induced heart failure. PMID- 22066405 TI - [Effect of Limax lyophilized powder on bronchial asthma]. AB - OBJECTIVE: To study the effect of Limax lyophilized powder on bronchial asthma. METHODS: The allergic asthma model was established in guinea pigs by combined utilization of aluminum hydroxide and egg albumin to investigate the effect of Limax lyophilized powder on the bronchial flow and on the level of inflammator in bronchoalveolar lavage and serum. RESULTS: The mortality of asthma laboratory guinea pigs was reduced and the incubation period of asthma was extended significantly in Limax lyophilized powder groups. Its antiasthmatic effect was as efficient as the control drug (aminophylline). The leucocyte count was decreased in peripheral blood and the bronchoalveolar lavage fluid. The infiltration of pulmonary tissues eosinophil was also significantly reduced. Further more,the most efficient effects was showed in Limax lyophilized powder at the moderate dosage (63 mg/kg). The bronchial perfusion flow was increased and the level of IL 2 and IL-4 in blood serum and bronchoalveolar lavage fluid was decreased obviously in the aminophylline group and Limax lyophilized powder groups at moderate and high dosage. CONCLUSION: Limax lyophilized powder could inhibit bronchial asthma evidently. PMID- 22066406 TI - [Effect of total alkaloid of Sophora alopecuroides on SW480 cells and Balb/c nude mice tumor xenograft]. AB - OBJECTIVE: To study the anti-tumor effect of total alkaloid of Sophora alopecuroides (TASA) on human colon adenocarcinoma SW480 cells and Balb/c nude mice tumor xenograft. METHODS: The effect of TASA on cell proliferation was assessed using MTT assay and the cell apoptosis was detected using Annexin V-FITC apoptosis assay. The nude mouse model bearing transplanted solid tumor SW480 was established. The changes of the volume and weight of the tumor were determined after treatment the mice with TASA. Fluorescence quantitative PCR was used to detect Caspase-3, Caspase-9 and BCL-2 mRNA expressions in the tumor. RESULTS: TASA inhibited the proliferation of SW480 cells in a dose- and time-dependent manner. The apoptotic rate of cells was the best when the concentration of TASA was 0.92 mg/mL at 48 hours. The volume and weight of the tumor xenograft in TASA groups were decreased when compared with those of the control group. The results of RT-PCR showed that TASA activated the pro-apoptotic Caspase-3 and Caspase-9 and lowered expressions of BCL-2. CONCLUSION: TASA can inhibit the growth of SW480 cells and the growth of transplanted solid tumor of human SW480 cell line, the mechanism of which involves the effect of Caspase-3, Caspase-9 and BCL-2 expression. PMID- 22066407 TI - [Effect of taspine derivatives on human liver cancer SMMC7721]. AB - OBJECTIVE: To analyse the inhibition effect of taspine derivatives on human Liver cancer SMMC7721 cell and its mechanism. METHODS: The effects of five taspine derivatives on SMMC7721 cell growth were determined by MTT. The flow cytometry was used to determine the cell cycle. The effects of Tas-D1 on the EGF and VEGF in SMMC7721 cell were determined by ELISA. The mRNA level of EGF and VEGF in SMMC7721 cell was determined by RT-PCR. RESULTS: The MTT assay demonstrated that the taspine derivative Tas-D1 significantly inhibited the growth of SMMC7721 cell in a dose-dependent manner. Cell was stopped at S phase by Tas-D1. Tas-D1 inhibited the expression of EGF and VEGF and their mRNA in a dose-dependent manner (P<0.05). CONCLUSIONS: The taspine derivative Tas-D1 can inhibit the growth of human Liver cancer SMMC7721 cell and change cell cycle, which may be related to the inhibition of EGF and VEGF expression. PMID- 22066408 TI - [Optimization of microwave-assisted extraction with RSM and HPLC determination for three iridoid glycosides in Cornus officinalis]. AB - OBJECTIVE: To establish a method of microwave-assisted extraction and high performance liquid chromatographic (HPLC) for simultaneous determination of three iridoid glycosides including loganin, sweroside and cornuside in Cornus officinalis. METHODS: The extraction conditions of microwave power,ethanol concentration, liquid to sample ratio were optimized with a response surface methodology (RSM); Three constituents were separated on an Agilent TC-C18 column by gradient elution using acetonitrile and water as the mobile phase. The flow rate was 1.0 mL/min. The detection wave length was 240 nm. RESULTS: The optimal conditions of microwave extraction were as follows: microwave power 400 W, ethanol concentration 72%, liquid to sample ratio 15 mL/g, the extraction time 10 min, the extraction times 2; The HPLC peak areas of all the constituents showed good linearity (r>0.9994) in the range of the tested concentration,the average recoveries of the method were 98.68%, 98.24% and 98.29%, respectively. CONCLUSIONS: The established method of microwave-assisted extraction and HPLC simultaneously determination has the advantages of convenient, precision and reliability. It can be used in simultaneous determination of three iridoid glycosides in Cornus officinalis. PMID- 22066409 TI - [Study on preparation of salidroside and polysaccharide in Rhodiola crenulata]. AB - OBJECTIVE: To optimize the preparation process of salidroside and polysaccharide in Rhodiola crenulata. METHODS: Water-extraction and alcohol-precipitation was used. The effect of added water volume, decoction time and frequency on water extracting process was investigated by L9 (3(4)) orthogonal design using extraction rate, content of salidroside and polysaccharide as the assessment indexes. The effect of liquor strength and ethanol concentration on alcohol precipitating process was investigated as well, using content of salidroside and polysaccharide as the assessment indexes. RESULTS: The optimum conditions for water-extracting process were as follows: decocting 3 times, and each time adding 8 fold of water and extracting 2 h. For alcohol-precipitating process,it was that liquor strength was 0.4 g/mL, and ethanol concentration in liquor was 70%. CONCLUSION: The optimized process has guidance for the development and comprehensive utilization of this plant. PMID- 22066410 TI - [Optimization of ultrasonic-assisted extraction of total flavonoids from leaves of the Artocarpus heterophyllus by response surface methodology]. AB - OBJECTIVE: To investigate the ultrasonic-assisted extract on of total flavonoids from leaves of the Artocarpus heterophyllus. METHODS: Investigated the effects of ethanol concentration, extraction time, and liquid-solid ratio on flavonoids yield. A 17-run response surface design involving three factors at three levels was generated by the Design-Expert software and experimental data obtained were subjected to quadratic regression analysis to create a mathematical model describing flavonoids extraction. RESULTS: The optimum ultrasonic assisted extraction conditions were: ethanol volume fraction 69.4% and liquid-solid ratio of 22.6:1 for 32 min. Under these optimized conditions, the yield of flavonoids was 7.55 mg/g. CONCLUSION: The Box-Behnken design and response surface analysis can well optimize the ultrasonic-assisted extraction of total flavonoids from Artocarpus heterophyllus. PMID- 22066411 TI - [Rationality for dynamic detection of shikonin of Arnerbia euchroma in industrial process]. AB - OBJECTIVE: To discover reasons for great loss of shikonin during the concentrating process of percolate of Arnerbia euchroma (Royle) Johnst and develop a reasonable method for determination of shikonin. METHODS: Shikonin was selected as index, optimized chromatographic condition was used for analyzing the affection of alcohol content and crude drug content of sample solution on determination of shikonin, furthermore, reasonable sample preparation and determination methodology was examined and defined. RESULTS: The optimized chromatographic condition was as follows: shikonin was analyzed with a Zorbax Extend C-18 column (4.6 mm x 250 mm, 5 microm), methanol: water (82: 18) as the mobile phase, the column was maintained at 35 degrees C, the flow rate was 1.0 mL min(-1), detection wavelength was set at 516 nm and the time for analysis reduced from 40 min to 24 min. Alcohol content of sample solution influenced determination results significantly, peak area of equal content shikonin in low alcohol content (<40%) was only about 20% - 30% of that of high alcohol content (>70%), the reasonable content of sample solution were 0.0167 - 0.083 g mL(-1) with alcohol content above 40%. The method showed good linearity, precision, reproducibility and accuracy. CONCLUSION: The alcohol content of sample solution correlated with peak area closely for the first time, which indicate another important reason for "great loss" of shikonin during concentration process is that too much low ethanol content in test solution leads too much low results. The new method can detect shikonin more effectively and more reasonably and can monitor production process with high efficiency and low cost. PMID- 22066412 TI - [Study on the enzyme extraction process of hypericin by pectinase]. AB - OBJECTIVE: To explore the best enzyme and optimal conditions for extracting Hypericin from Hypericum perforatum. METHODS: Chose the best enzyme from Pectinase, Xylanase, Glucanase, beta-Glucanase and Enzyme (SPE-007A). The effeet of solid-liquid ratio enzyme dosage, PH, temperature and the extraction time were investigated by L9 (3(4)) orthogonal design using extraction rate and the content of Hypericin as assessment index. RESULTS: The best enzyme was Pectinase and the optimum extraction process was as follows: PH 4.6, enzyme dosage 1.5%, temperature 50 degrees C, extraction time 5 h, liquid-solid ratio 15 times. CONCLUSION: This method is efficient and stable. It could be used in the future research of Hypericum perforatum. PMID- 22066413 TI - [Network pharmacology and drug discovery]. AB - The pharmaceutical industry has historically relied on particular families of 'druggable' proteins against which to develop compounds with desired actions. But proteins rarely function in isolation in and outside the cell; rather, proteins operate as part of highly interconnected cellular networks. Network pharmacology is an emerging area of pharmacology which utilizes network analysis of drug action. By considering drug actions in the context of the cellular networks, network analysis promises to greatly increase our knowledge of the mechanisms underlying the multiple actions of drugs. Network pharmacology can provide new approaches for drug discovery for complex diseases. This review introduced the recent progress of network pharmacology and its importance to understand the mechanism of drug actions and drug discovery. PMID- 22066414 TI - [Abnormality of renin-angiotensin system in podocyte dysfunction in diabetic kidney disease]. AB - Diabetic kidney disease (DKD) is currently the leading cause of end-stage renal disease (ESRD). DKD is stamped by proteinuria and progressive renal dysfunction. Excessive activation of RAS under hyperglycemic condition is associated with the development of DKD. Suppression of RAS markedly reduces proteinuria and retards progression of DKD in clinic. Podocyte forms the final barrier to protein in glomerular filtration. Podocyte injury leads to abnormality in glomerular filtration permeability, results in proteinuria. Various components of RAS have been identified to be expressed in podocyte. Here we reviewed the progress on RAS in regulating the function of podocyte and progress of DKD. PMID- 22066415 TI - [New perspectives in the treatment of diabetes by interfering with glucagon signaling pathway]. AB - Glucagon, a hormone secreted from the alpha cell of the endocrine pancreas, is a major counterpart to insulin. After released into blood, glucagon will combine with its receptor in targeting tissues and form a compound, which then activates its signaling pathway, produces cAMP, promotes gluconeogenesis and glycogenolysis and inventually increases blood glucose. Researches recently display that it will be an important addition to treatment method by inhibiting synthesis and secretion of glucagon, neutralizing circulating glucagon, using glucagon receptor antagonists and prohibiting gene expression of glucagon receptor. PMID- 22066416 TI - [Glutamate receptors and gamma-aminobutyric acid receptors in pancreatic cells]. AB - Glutamate and gamma-aminobutyric acid (GABA) receptors are mainly expressed in central nervous system and play critical roles in neural signal transduction. It has been demonstrated that glutamate and GABA receptors are also found in pancreatic islets. Interestingly, almost all of glutamate and GABA receptor subunits are present in islets. Here, we summarize current progresses of these receptors in islets, focusing on there expressions, physiological implications, interactions, as well as a novel approach to investigate roles of the receptors in islets slice. All these investigations will potentially supply new understanding of working mechanism of these receptors in islet and also shed a new insight for neuroscientific research. PMID- 22066417 TI - [Specific expression of microRNA in different tissues of nervous system and expression changes in nerve regeneration]. AB - MicroRNA is a class of endogenous non-coding RNA, which regulates the expression of target genes at the post-transcriptional level. In recent years, researches have shown that microRNA expresses specifically and plays an important role in the nervous system under physiological condition. Furthermore, the distribution and expression level of microRNA were changed after the injury of nervous system, which presents important effect on nerve regeneration. This effect of microRNA is significant to the clinical diagnosis and treatment on the injury of nervous system. PMID- 22066418 TI - [Research progress in relations between renin angiotensin system and diabetic cardiomyopathy]. AB - Renin-angiotensin system (RAS) is activated in diabetes. The rise of angiotension II (Ang II) stimulates the cardiac fibroblast proliferation and the alteration of collagen metabolism through AT1 receptor on cell surface, causing the myocardium interstitial and perivascular fibrosis, and the ventricular myocardium rigidity and diastolic function disturbance, leading to the clinical symptoms of diabetic cardiomyopathy (DCM). The main members of RAS including Ang II, Ang-(1-7), Ac SDKP and ATR play the important role in the development of DCM. This article reviewed the interactions between RAS and endothelin (ET), reactive oxygen species (ROS), transforming growth factor-beta 1 (TGF-beta 1), nuclear factor kappa b (NF-kappaB), signal transduction system and apoptosis in DCM. PMID- 22066419 TI - [Research advance of the protective role of PACAP in the nervous system diseases]. AB - In the central nervous system, pituitary adenylate cyclase-activating polypeptide (PACAP) exerts different actions as neurotransmitter, neuromodulator, neurotrophic and neuroprotective factors via multiple signaling pathways. PACAP plays an important protective role in the nervous system diseases, such as focal cerebral ischemia, traumatic brain injury (TBI), schizophrenia, anxiety disorders Parkinson's disease and Alzheimer's disease. Now, we reviewed the research advances about the protective role of PACAP in the nervous system diseases. PMID- 22066420 TI - [The progress study of HDAC2 function in diseases]. AB - HDAC2 is a histone acetyltransferase I, promotes the hormone and cytokine dependent signal transduction. HDAC2 is unique marker for oral, prostate, ovarian, endometrial or gastric cancer, and related with muscle and heart related diseases, it plays an important role in embryonic development and neural function. As the precise target of drug development and drug intervention technology, HDAC2 has been proved to be an effective treatment. In this paper, the role of HDAC2 is summarized in health and related diseases. PMID- 22066421 TI - [Progress in research of arachidonic acid-cytochrome P450 pathway in diabetes]. PMID- 22066422 TI - [Advances in studies on the protein homocysteinylation]. PMID- 22066423 TI - [TMEM16/ANOCTAMIN: the newest chloride channel family]. PMID- 22066424 TI - [Canonical transient receptor potential and cell proliferation]. PMID- 22066425 TI - [Progress in liver X receptor and neuroimmunology]. PMID- 22066426 TI - [Progress in the research of ghrelin and reproductive system]. PMID- 22066427 TI - [The Rho/Rho kinase signaling pathway and vessels contraction]. PMID- 22066428 TI - [A new concept of the nerve conduction: the nerve conduction of excitation without action potentials]. PMID- 22066429 TI - [NALP3 inflammasome and non-infectious inflammatory diseases]. PMID- 22066430 TI - [Feasibility analysis of application of future contract in Chinese materia medica transaction]. AB - With the rapid development of Chinese economy, the traditional Chinese medicine has been paid more attention worldwide because of its therapeutic effect and the special health care function. The future contract which was born under the modern economic system, by its price discovery function and the circumvention risk function, occupies the main superiority in the commodity exchange. The traditional Chinese medicine, which has a glorious transaction history commodity, whether future contract could be used to carry on the transaction still to lack the scientific examination. This article reviewed traditional Chinese medicine tradition trading mode forms with in the evolution foundation, summarized the Chinese materia medica tradition trading mode characteristic, discussed necessity and feasibility of the future contract as a supplement sale way for traditional Chinese medicine transaction. It also forecasted possible risk of future contract, proposed the preliminary implementation method for traditional Chinese medicine future contract. PMID- 22066431 TI - [Network target: a starting point for traditional Chinese medicine network pharmacology]. AB - Understanding the interactions between numerous chemical compounds of herbs or herbal formulae and complex biological systems related with diseases or traditional Chinese medicine (TCM) syndromes is one of great dilemmas in current studies on TCM. To address such a difficult issue, we propose a novel concept and methodology of "Network Target" based on our previous works and from the perspective of network pharmacology as well as systems biology. The network target treats a disease-specific biomolecular network as a target to help design and predict the best possible treatments. Focused on mapping disease phenotypes and herbal compounds into biomolecular networks and then calculating, analyzing and predicting the mechanism of their mutual interactions, the network target approaches will facilitate discovery of effective compounds and their combinations, elucidation of mechanistic relationships between herbal formulae and diseases or TCM syndromes, and development of rational drug designs for TCM. In this paper, our recent progresses on the methodology of Network Target and its applications in herbal medicine are reviewed to provide reference for the coming TCM network pharmacology. PMID- 22066432 TI - [Advances in studies on metabolism and biotansformation of ginsenosides in vitro]. AB - As a famous traditional Chinese medicine, ginseng's metabolism has been a hot spot in recent years. In this review, relevant literatures on the research progress of the metabolism of ginsenosides in vitro have been introduced. This review focuses on artifical juice metabolism, intestinal bacteria metabolism, microbial and enzymatic biotransformation of ginsenosides. Main metabolic pathways of ginsenosides in vitro are also analyzed, which will provide a reference for the systematic study on metabolism of ginsenosides. PMID- 22066433 TI - [Effect of Tongfeng trace elements nutrient balance agent on growth, physiological characteristics and content of active constituents of Glycyrrhiza uralensis]. AB - OBJECTIVE: To investigate the effects of Tongfeng trace elements nutrient balance agent on the various growth indicators, physiological indicators, and the contents of liquiritin and glycyrrhizic acid in one-year old Glycyrrhiza uralensis. METHOD: The plants of G. uralensis growing in Chifeng of Inner Mongolia and medicinal garden of Beijing University of Chinese Medicine were fertilized for two times, respectively. The photosynthetic physiological indicators were measured by LI-6400 photosynthetic instrument. The pigments and antioxidase activities of the leaves were determined. Then contents of liquiritin and glycyrrhizic acid in the plants were determined by HPLC. RESULT: The application of this trace element nutrient balance agent could significantly improve the height, chla and chlb, and the photosynthetic physiology indicator such as P(n), C(i), and G(s). Similarly, it could significantly increase the fresh weight of shoots and dry weight of the roots. Compared with control block (CK), the fertilizer which was diluted by 300 times (T(1)) and 600 times (T(2)) significantly increased the content of glycyrrhizic acid by 24.72% and 20. 23%. There was significant difference between different treatments (P < 0.05). CONCLUSION: The Tongfeng trace elements nutrient balance agent could promote growth, physiology and the content of active constituents of G. uralensis, especially the effect of T(1) was superior to T(2). PMID- 22066434 TI - [Influences of enhanced UV-B radiation and drought stress on biomass accumulation and allocation of Fagopyrum dibotrys]. AB - OBJECTIVE: To study the influences of enhanced UV-B radiation and drought stress on the biomass accumulation and allocation of Fagopyrum dibotrys, and so as to provide a theoretical basis for the cultivation, the protection and use of F. dibotrys. METHOD: By experiment of potted plant, the biomass accumulation and allocation of F. dibotrys were measured under different drought stresses and UV-B radiations. RESULT: In conditions of adequate water, enhanced UV-B radiation significantly reduced biomass accumulation to root, biomass accumulation to leaves, total biomass accumulation and biomass allocation to root in F. dibotrys, while it could increase biomass allocation to stem. In conditions of moderate drought stress, enhanced UV-B radiation increased biomass accumulation to root, biomass accumulation to stem and biomass accumulation to root. In the conditions of severe drought stress, enhanced UV-B radiation increased biomass accumulation to root, it also could lead in a certain increase to biomass accumulation to stem. Biomass allocation to root, stem and leaves was not sensitive to enhanced UV-B radiation. CONCLUSION: The influences of enhanced UV-B radiation in simulation and drought stress on the biomass accumulation and allocation of F. dibotrys were determined by water conditions and different apparatus. Overall, we verified that enhanced UV-B radiation would reduce the influences of biomass accumulation of F. dibotrys by drought. PMID- 22066435 TI - [Study on seed quality of Achyranthes bidentata]. AB - OBJECTIVE: To study the seed quality of Achyranthes bidentata from different sources and establish a standard of seed quality grading. METHOD: Seed weight and moisture content determination, germination test, purity analysis were carried out by 100 grains method, high-temperature drying, double deck filter paper and GB/T354. 3-Seed Testing for Crops methods respectively. Eight collections were planted in several field plots. RESULT: The 1 000 grains weight of 33 collections is 0.69 to 3.54 g with a variance coefficient 24.83%, the germination rate between 19.02% to 99% with a variance coefficient 38.24%. Seed moisture content and purity showed no significantly difference. K-means cluster analysis showed that 33 collections were divided into 3 grades: the first grade including 23 collections, the second and third grade including 5 collections respectively. Eight collections showed different field growth and yield characters. CONCLUSION: There are significant differences in seed quality of A. bidentata, so the classification management is needed in medicinal materials market. Germination test is an effective method before cultivating. PMID- 22066436 TI - [Study on quality of medicinal material of Thesium chinense]. AB - OBJECTIVE: To study the quality of medicinal material of Thesium chinense. METHOD: The active ingredients of total flavonoids, kaempferol, mannitol, polysaccharides were selected as the evaluative indicators to comprehensively evaluate the quality of medicinal material of T. chinense. RESULT: The total flavone 3.38%, kaempferol 0.984 7 mg x g(-1), mannitol 6.12%, polysaccharides 14.08% and water soluble extract 30.28% were measured in the sample of T. chinense. There was a certain correlation among these selected active ingredients. The compositions of most biological activities component in T. chinense of different populations were similar, but the contents were different significantly. The content of activities component in T. chinense showed a general tendency of declining during growth period and with the increase time of storage. CONCLUSION: Flavone, kaempferol, mannitol, polysaccharides should be selected as the indicators to evaluate the quality of medicinal material of T. chinense. PMID- 22066437 TI - [Effects of waste batteries leaching solution stress on resistance physiological indices of volatile constituents from Schizonepeta tenuifolia]. AB - OBJECTIVE: The effect of waste batteries leaching on the seedling growth and volatile constituents in leaves of Schizonepeta tenuifolia was assayed. METHOD: The different concentrations of waste batteries leaching on the seedling growth were discussed. Volatile compounds were analyzed by solid-phase micro-extraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS). RESULT: The results indicated that S. tenuifolia showed resistance to heavy metal polluting, but the high rate of waste batteries leaching had the inhibiting effect to seedlings growth. The waste batteries leaching cause the major volatile constituents in leaves of S. tenuifolia was changed greatly under waste batteries leaching solution stress. CONCLUSION: Heavy metal leached by waste batteries had great effect on growth of S. tenuifolia, reducing its value for food and medical purposes. PMID- 22066438 TI - [Isolation and characterization of promoter of ADS from Artemisia annua]. AB - OBJECTIVE: To try to find the ways to enhance the expression of ADS gene encoding amorpha-4,11-diene synthase, a key enzyme in artemisinin biosynthesis pathway catalyzing the formation of amorpha-4,11-diene from farnesyl diphosphate, and accelerate the artemisinin synthesis, the promoter of ADS was isolated and characterized. METHOD: 5' untranslated regions of ADS were isolated from Artemisia annua with PCR. For functional characterization, the isolated fragment was fused with GUS reporter gene and introduced into Nicotiana tabacum by Agrobacterium-mediated transformation. The GUS expression regulated by 5' untranslated regions of ADS in transgenic N. tabacum under the normal or stressed conditions were detected by histochemical staining and quantitative spectrophotometry assay. RESULT: The 2 448 bp DNA fragment upstream of ADS coding sequence was isolated from A. annua and introduced into N. tabacum. Histochemical staining showed that the isolated fragment conferred stable GUS expression in transgenic plants. The quantitative results showed that the GUS activity in transgenic tobacco plants treated by low-temperature (4 degrees C) and ultraviolet irradiation were 1. 6 and 2.2 folds higher than that in the controls. CONCLUSION: It was suggested that the isolated fragment had promoter activity and maybe responsive to adverse environmental stresses. PMID- 22066439 TI - [Comparision of adsorption-desorption dynamics of huanglian jiedu decoction using different macroporous resins combinations]. AB - OBJECTIVE: To establish the techniques for the purification of Huanglian Jiedu decoction by macroporous resins combinations, and to lay the foundation of improvement of dosage forms in clinical application and realization of industrialized production about Huanglian Jiedu decoction. METHOD: Four kinds of macroporous resins (X-5, S-8, HPD100, AB-8) were chosen and combined in six different forms. Adsorption and desorption experiments were carried out and contents of six index constituents, gardenoside, baicalin, palmatine, berberine, baicalein and wogonin, in different groups were compared before and after purification. RESULT: Adsorption rates of six index constituents in Huanglian Jiedu decoction of different combinations of macroporous resins groups were all nearly 100%, but desorption rates had remarkable differences. CONCLUSION: Through comprehensive comparison, macroporous resins combination 6 resulted in high contents of index suitable relatively. It is suitable for purification of Huanglian Jiedu decoction. PMID- 22066440 TI - [A new water-soluble lubricant of tablets-L-leucine combined with PEG6000]. AB - OBJECTIVE: To prepare an effective and water-soluble lubricant. METHOD: Co sprayed lubricant (L-leucine and polyethylene glycol 6000 co-sprayed according to a certain proportion) and mixed lubricant (the physical mixture of spayed L leucine and crushed polyethylene glycol 6000) were prepared and polyethylene glycol 6000, L-leucine, magnesium stearate, sodium stearyl fumarate and sodium chloride are crushed and sieved, respectively. Residual force, appearance of solution and disintegration time were considered as response variables of the lubrication effect to evaluate different lubricants. The changes of the co sprayed lubricant were studied by differential scanning calorimetry, fourier infrared, electronic scanning microscope and X-ray diffraction. RESULT: The efficacy of co-sprayed lubricant is better than other lubricants. Efficacy is improved by external form change without inner components and crystal changes. CONCLUSION: Co-sprayed lubricant is a good water soluble tablet lubricant which has good efficacy. PMID- 22066441 TI - [Chemical reaction and products in processed Cibotium barometz]. AB - OBJECTIVE: To investigate the chemical variation and its mechanism in processing of Cibotium barometz. METHOD: The methods of TLC and HPLC were carried out to identify the chemical variation in processing of C. barometz, and the compounds changed significantly were isolated by chromatography. RESULT: Chemical components were changed significantly in processing of C. barometz. CONCLUSION: Maillard reaction is involved in the process of rhizome C. barometz, which may be contributed to the activity between raw and processed C. barometz. PMID- 22066442 TI - [Variation of 4 kinds of compounds in Psoralea corylifolia processed by different methods]. AB - OBJECITVE: To established an efficient method for simultaneous quantification of 7 compounds belonging to 4 chemical types in Psoralea corylifolia processed by different methods, and to elucidate variations of 4 kinds of compounds in different processed P. corylifolia. METHOD: The chromatographic separation was performed on an ACUITY C18 column using acetonitrile and 0.1% formic acid aqueous solution in the gradient elution at 0.4 mL x min(-1). Detection wavelength was set at 246 nm. Column temperature was fixed at 50 degrees C. RESULT: The 4 kinds of compounds including psoralenoside, isopsoralenoside (benzofuran glycosides), psoralen, isopsoralen, psoralidin (coumarins), bavachin (flavonoids), and bakuchiol (meroterpenes) were separated in 25 min. The correlation coefficients of those compounds were over 0.9993 in the tested range. The intra- and inter-day precisions were below 1.5%. The average recoveries ranged from 99.2% to 106%. CONCLUSION: This method is simple, rapid and accurate, which can be used for the determination of the 4 kinds of compounds in different processed P. corylifolia. In P. corylifolia processed by different methods, the contents of benzofuran glycosides, flavonoids, and meroterpenes in P. corylifolia processed by Leigong's method decrease obviously, while the contents of psoralen and isopsoralen increase significantly. PMID- 22066443 TI - [Study on network compatibility of metabolisms in vivo rat for volatile oil in houttuyniae herba and 2-undecanone]. AB - OBJECTIVE: To study on the differences of metabolites in the blood of rats after injection or oral administration of volatile oil in Houttuyniae Herba and of 2 undecanone in order to validate hypothesis of network compatability and to establish the theoretical foundation of elucidating metabolic mechanism for multiple constituents in Chinese Material. METHOD: A gas chromatography-mass spectrometry method was employed for qualitative determination of the metabolites in blood of rats by injection or oral administration of volatile oil in Houttuyniae Herba and of 2-undecanone, which were compared with the differences between binary two drugs as well as two administration. RESULT: There were 45 kinds of ingredients in volatile oil for original materials for Houttuyniae Herba, and 53, 69 kinds of metabolites were detected in blood of rats for oral administration of volatile oil in Houttuyniae Herba, and 2-undecanone, respectively, whereas 52, 42 kinds of metabolites were detected for injection administration. Although there were various constitutes, i. e. single versus multiple ingredients, administrated by various ways, i. e. oral versus injection, the metabolites were so similar with each manners, in which alpha-pinene and beta myrcene occurred in two constitute forms and two administrations, while there were 18, 13 kinds of ingredients for oral or injection administration of volatile oil in Houttuyniae Herba, i. e. 34%, 25% of total ingredients, respectively, and 17, 15 kinds of ingredients, i. e. 24.6%, 35.7% for that of, 2-undecanone, respectively, on average of 29.8% that suggested one of third as co-metabolites. CONCLUSION: There are network compatibility existed in metabolism of the houttuynia volatile oil in rats, and similar metabolic pathways in accordance with original plant, among their ingredients no matter alone or multiple constitute forms and oral or injection administration. PMID- 22066444 TI - [Rubrofusarin glucosides of Berchemia polyphylla var. leioclada and their scavenging activities for DPPH radical]. AB - OBJECTIVE: To study the rubrofusarin glucosides from whole plants of Berchemia polyphylla var. leioclada, and their scavenging activities for 2,2-diphenyl-1 picrylhydrazyl (DPPH) radical. METHOD: The chemical constituents were isolated and purified via repeated silica gel and Sephadex LH-20 column chromatography. Their structures were elucidated by spectral analysis and the compounds were tested for their scavenging activities on DPPH radical. RESULT: Three rubrofusarin glucosides compounds were isolated and identified as rubrofusarin-6 O-beta-D-glucopyranoside (1), rubrofusarin-6-O-beta-D-(6'-O-acetyl) glucopyranoside (2), rubrofusarin-6-O-alpha-L-rhamnosyl-(1-6) -O-beta-D glucopyranside (3). Three isolated compounds showed strong scavenging activities on DPPH radical, the concentration of half elimination ratio( micromol x L(-1)) of VitC and Compounds 1-3 were 18.2, 40.5, 23.3 and 13.6, respectively. CONCLUSION: Compounds 1-3 were isolated from this plant for the first time and compound 2 was a new compound. They showed significant antioxidant activity, and the scavenging activity of compound 3 was a little stronger than that of VitC. PMID- 22066445 TI - [Diterpenoids from Chinese eaglewood]. AB - Column chromatography on silica gel, Sephadex LH-20, semi-preparative HPLC were used to separate and purify the compounds from the petroleum ether and ethanol extract of Chinese eaglewood. Nine compounds were isolated. On the basis of their spectroscopic data, their structures were identified as dehydroabietic acid (1), methyl dehydroabietate (2), methyl 7-oxodehydroabietate (3), 7alpha, 15 dihydroxydehydroabietic acid (4), 7alpha-hydroxypodocarpen-8(14)-en-13-on-18-oic acid (5), pimaric acid (6), pimarol (7), 18-norpimara-8 (14), and 15-dien-4alpha ol (8), 18-norisopimara-8 (14), 15-dien-4beta-ol (9). All of the compounds were isolated from this plant for the first time, and compounds 5, 8 and 9 are norditerpenoids. PMID- 22066446 TI - [Liposolubility constituents from leaves of Aquilaria sinensis]. AB - OBJECTIVE: To study the chemical constituents of the leaves of Aquilaria sinensis. METHOD: The compounds were isolated and purified by the methods of solvent extraction and chromatographic technique, and their structures were identified on the basis of the analyses of spectral data. RESULT: Eleven compounds were obtained and identified as beta-sitosterol (1), hexacosanic acid (2), cryptotanshinone (3), 2alpha-hydroxyursane (4), dihydrotanshinone I (5), tanshinone I (6), tanshinone II(A) (7), 2alpha-hydroxyursolic acid (8), p hydroxybenzoic acid (9), hydroquinone (10), and daucosterol (11), respectively. CONCLUSION: All compounds except for compound 9 were isolated from the leaves of A. sinensis for the first time. PMID- 22066447 TI - [Study on triterpenes from Solanum torvum]. AB - OBJECTIVE: To study on the chemical constituents of Solanum torvum. METHOD: The aerial parts of S. torvum swartz were extracted with 95% alcohol and the constituents were isolated and purified by chromatographic silica gel and Sephadex LH-20. Their structures were determined by NMR and MS spectral analysis. RESULT: Six triterpenes were isolated and identified as 3beta-acetyloleanolic acid (1), 3-O-acetyl-11alpha, 12alpha-epoxy-oleanan-28, 13beta-olide (2), oleanolic acid (3), ursolic acid (4), 2alpha-hydroxy-oleanolic acid (5), 2alpha, 3beta-dihydroxyursolic acid (6). CONCLUSION: All compounds were obtained from this plant for the first time. PMID- 22066448 TI - [Studies on new hydrolysate of aconitine using HPLC-MS(n) and quantum chemistry calculation]. AB - OBJECTIVE: To study the new hydrolysate of aconitine using HPLC-MS(n) and quantum chemistry calculation. METHOD: The HPLC method was applied in gradient elution program and the mass spectrometry was in positive ion mode. Geometries of the possible hydrolysates were optimized at DFT/6-31G(d) level. RESULT: The new hydrolysate was found and its protonated molecularions was at m/z 482. The quantum chemistry calculation results show that the product of elimination reations at C8 and C15 got the lowest energy conformation. The compound at m/z 482 was decluced to be the hydrolysate of carbony at C15. CONCLUSION: Delydration aconine was detected for the first time and the new hydrolysis pathways of aconitine in water were deduced. PMID- 22066449 TI - [Correlation of DNJ between taxilli herba and its host-plants]. AB - OBJECTIVE: To study the correlation of 1-deoxynojirimycin (DNJ) between Taxilli Herba parasitized in mulberry and its host-plants. METHOD: The contents of DNJ of Taxilli Herba parasitized in mulberry and non-mulberry were determined by RP HPLC. DNJ was extracted with 0.05 mol x L(-1) HCl, and then detected by fluorescence detector after derivatized with FMOC-Cl at pH 8.0 with borate buffer. The separation was performed on an Agilent C18 (4.6 mm x 250 mm, 5 microm) column with a mobile phase of acetonitrile-0.1% aqueous acetic acid (51: 49) at a flow rate of 1.0 mL x min(-1). The wavelength of fluorescence detector was operated at lambda(EX) = 254 nm and lambda(EM) = 322 nm. RESULT: The linear range of DNJ was 3.72-37.2 mg x L(-1) (r = 0.999 9). The average recovery was 96.42%. The contents of DNJ in mulberry and Taxilli Herba parasitized in mulberry were 1.39-10.16 mg x g(-1) and 0.46-2.72 mg x g(-1), respectively. However, the contents of DNJ could not be detected in Taxilli Herba parasitized in non mulberry and its host-plants. CONCLUSION: As the characteristic constituent of mulberry, DNJ was accumulated in Taxilli Herba This method can be applied to the quality control of Taxilli Herba from mulberry. PMID- 22066450 TI - [Determination of underivatized glycine and proline in vinegar turtle shell by HPLC-ELSD]. AB - OBJECTIVE: To establish a method to determine the underivatized glycine (Gly) and proline (Pro) in vinegar turtle shell. METHOD: An HPLC-ELSD method was conducted on a Prevail C18 column (4.6 mm x 250 mm, 5 microm) with the mobile phase of acetonitrile and 0.7% trifluoroacetic acid solution (containing 5.0 mmol x L(-1) heptafluorobutyric acid), and elution time was 15 min. RESULT: The calibration curves were showed good linearity within the concentration range of 0.14-0.6 g x L(-1). The average recoveries were 101.2% and 102.5%, and RSD were 1.9% and 2.5%, respectively. CONCLUSION: Since this method needs neither the special amino acid analyzer nor derivation of amino acid., it is efficient, simple and accurate., which could be used for quality control of vinegar turtle shell. PMID- 22066451 TI - [Determination of four alkaloids in Corydalis decumbens by HPLC]. AB - OBJECTIVE: To establish a quantitative HPLC method for determination of protopine, palmatine hydrochloride, bicuculline and tetrahydropalmatine, in Corydalis decumbens. METHOD: The separation was performed on a ZORBAX Eclipse XDB C18 column (4.6 mm x 150 mm, 5 microm) at a flow rate of 1.0 mL x min(-1) using mixtures of two solvents [A(20 mmol x L(-1) ammonium acetate)-B(acetonitrile)]: with a gradient elution. The column oven temperature was 30 degrees C and the detection wavelength was set at 280 nm. RESULT: The 4 alkaloids were well separated by this HPLC method. Linearifies of protopine, palmatine hydrochloride, bicuculline and tetrahydropalmatine were good in the ranges of 1.44-46.0 (r = 0.999 4), 1.2640.2 (r = 0.999 8), 1.37-44.0 (r = 0.999 9), and 1.3643.6 mg x L( 1) (r = 0.999 9), respectively. The average recoveries were 98.2% with RSD 2.7% for protopine, 101.9% with RSD 2.5% for palmatine hydrochloride, 102.8% with RSD 3.5% for tetrahydropalmatine, and 98.8% with RSD 3.1% for tetrahydropalmatine. CONCLUSION: This method is proved to be convenient, reliable and accurate., and it can be used for quality control of C. decumbens. PMID- 22066452 TI - [Study of molecular mechanisms of fuyuan capsule, icariin and arasaponin R1 in treatment of osteoarthritis]. AB - OBJECTIVE: To study the molecular mechanisms of Fuyuan capsule serum containing, icariin and arasaponin R1 in the treatment of osteoarthritis from the urokinase type plasminogen activator (uPA) system. METHOD: Chondrocytes were isolated, cultured and identified using type II collagens immunostaining. After stimulating with TNF-alpha 10 microg x L(-1), 1 h, then the chondrocytes were treatment with glucosamine hydrochloride 25 g x L(-1), 20% Fuyuan capsule serum containing, icariin 12.5 mg x L(-1), arasaponin R1 125 mg x L(-1), icariin 12.5 mg x L(-1) + arasaponin R1 125 mg x L(-1). After 2 h, expression of uPA and nuclear factor kappa B (NF-kappaB P65) mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR), the activities of NF-kappaB(P65) combine DNA were determined by electrophoretic mobility shift assays (EMSA), 1kappaBalpha were detected by Western blotting. RESULT: Fuyuan capsule, icariin and arasaponin R1 could significantly reduce NF-kappaB (P65) activities and uPA mRNA expression, and increase expression of IkappaBalpha (P < 0.01), but no significant difference between all treatment groups. CONCLUSION: Fuyuan capsule and its two main active ingredients, icariin and arasaponin R1, could protect chondrocytes from damage through reducing the NF-kappaB (P65) activities, increasing the express of IkappaBalpha and then reducing uPA of chondrocytes. PMID- 22066453 TI - [Attenuation effects of compatible medicines on arsenical and lead toxicity of badu shengji san]. AB - Badu Shengji San(BDSJS) is a traditional Chinese medicine (TCM) used for drawing out toxin, eliminating suppuration and promoting granulation. Toxic minerals such as arsenic and lead are the two most important components of BDSJS. Previous hypothesis indicated that according to the compatibility theory of TCM, the toxicity of the entire BDSJS was weaker than that of arsenic and lead, respectively. In the present study, SD rats with injured skin were treated with distilled water and different composition of BDSJS (complete formulations, compatible herbs, mineral medicine containing arsenic and lead, mineral medicine containing arsenic and mineral medicine containing lead) once a day for consecutive 2 weeks. Kidney coefficient and urinary beta-N-acetyl glucosidase (NAG) were used as the indicators of renal toxicity and the content of malondiadehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH PX), glutathione (GSH) and metallothionein (MT) in the renal tissue were measured. Our data showed that kidney coefficient, the severity of renal pathological lesion and MT level in the kidney of the entire BDSJS group decreased significantly compared with arsenic and lead group. Additionally, the NAG content of the entire BDSJS group had the decreased trend. The kidney CuZn SOD level of the entire BDSJS group had the increased trend, but the MDA, GSH-PX, GSH level had no obvious difference. Our results suggested that compatible herbs in BDSJS relieved renal injury induced by arsenic and lead, and the attenuation mechanism may be related to MT and CuZn-SOD, but not to MDA, GSH-PX and GSH directly. PMID- 22066454 TI - [Effects of isopsoralen on bone marrow stromal stem cells differentiate and proliferate in vitro]. AB - OBJECTIVE: To investigated the effects of isopsoralen on bone marrow stromal stem cells (BMSCs) differentiate and proliferate in vitro. METHOD: The stratum of mononuclear cells were separated and collected from the rat bone marrow sample by the all bone marrow cell culture methods. The cells were cultured in DMEM contained 10% fetal bovine serum. The culture medium was changed after three days. Nine days later, cells were treatment by isopsoralen with the concentration 1 x 10(-5), 1 x 10(-4), 1 x10(-6), 1 x 10(-7) mol x L(-1). MTT method was used for the proliferated analyzing. Under the induced condition, the alkaline phosphatase (ALP) activity, calcium salt sediment yield and osteocalcin were measured at the 4, 8, 12, 16 d. At the fifteenth day, histochemistry dyeing for calcified tubercle and ALP was proceeded. Total RNA was isolated and the gene expression of bFGF, IGF-1, Osterix and Runx-2 were investigated by Real Time PCR. RESULT: The BMSCs proliferation refrained by isopsoralen with dose dependent. But it significantly enhanced osteogenesis, which was represented by the promotion of the ALP activity, calcium salt sediment yield, osteocalcin, and calcified tubercle amount. Besides, it also enhanced the mRNA level of bFGF, IGF-1, Osterix and Runx-2. CONCLUSION: The isopsoralen with the concentration 1 x 10(-5) mol x L(-1) can promote BMSCs differentiation to osteoblasts. It demonstrated the isopsoralen can prevent antiosteoporotic, which is an active part of the traditional Chinese medicine psoralea corylifolia. PMID- 22066455 TI - [Apoptosis inducing effect of tanshinone II(A) on human nasopharyngeal carcinoma CNE cells]. AB - OBJECTIVE: To investigate anticancer effect and potential mechanism of tanshinone II(A) (Tan II(A)) on human nasopharyngeal carcinoma cell line CNE cells. METHOD: Antiproliferative effect of Tan II(A) on CNE cells was evaluated by morphological examination, cell growth curves, colonial assay and MTT assay. Apoptosis detection was carried out using Hoechest 33258 and PI double-dyeing method. Intracellular Ca2+ concentration and mitochondria membrane potential were detected by fluorospectrophotometer. Bad and MT-1A transcript analysis in CNE cells was analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). RESULT: Tan II(A) could inhibit CNE cells proliferation in dose- and time-dependent manner. 50% inhibiting concentration of Tan II(A) on CNE cells in 24, 48, 72 h was 45.7, 24.8, 3.3 mg x L(-2), respectively. Typical apoptotic morphology such as chromatin aggregation was observed in CNE cells with Tan II(A) treated for 24 h, and the apoptotic inducing effect was in a dose-dependent manner. After treated with Tan II(A), intracellular Ca2+ concentration of CNE cells was increased, mitochondria membrane potential of the cells was decreased, relative mRNA level of Bad and MT-1A was up-regulated. CONCLUSION: Tan II(A) had anticancer effect on CNE cells through apoptosis via calcineurin-dependent pathway and MT-1A downregulation. PMID- 22066456 TI - [Effect of tetrandrine on nitroglycerin induced activation of satellite cells in trigeminal ganglia]. AB - OBJECTIVE: To evaluate the effect of tetrandrine (Tet) on nitroglycerin(GTN) induced activation of the satellite cells released inflammatory cytokines and to explore its mechanism. METHOD: Neonatal rat satellite cells of trigeminal ganglia were cultured and separated into three groups. Group CON: the cells were normal cultured; Group TGN: the cells were cultured with 0.55 mmol x L(-1) GTN; Group Tet: the cells were treated with 0.55 mmol x L(-1) GTN and 1 x 10(-7) mol x L(-1) Tet respectively. Cell viability after GTN and Tet was detected by AlamarBlue assay. The concentration change of intracellular Ca2+ ([Ca2+]i) in single satellite cell loaded with Fluo-3/AM was determined by laser scanning confocal microscopy. NF-kappaB and IL-1beta mRNA levels were determined by FQ-PCR. Through double-immunofluorescent staining identifies satellite cells and determines the expression of NF-kappaB protein. RESULT: Satellite cells activities decreased with GTN stimulating, but according to the viability and modality of the cells, 1 x 10(-7) mol x L(-1) Tet was the suitable prophylaxis. Tet can inhibit the elevation of cytosolic free calcium of rat satellite cell and decrease the mRNA and protein levels of NF-kappaB and the mRNA levels of IL-1beta. CONCLUSION: Via preventing Ca2+ influxion, Tet inhibited NF-kappaB activation of satellite cell which decreased IL-1beta expression. PMID- 22066457 TI - [Activity evaluation of components and preparation of effective components group of xiaoxuming decoction for anti-cerebral ischemic]. AB - OBJECTIVE: On basis of preliminary studies, to prepare the effective components group of Xiaoxuming decoction for anti-ischemic by combining chemical analysis with pharmacological activity screening. METHOD: Free radical scavenging was assayed by DPPH method; the cell viability injured by hydrogen peroxide, L glutamate, and hypoxia was determined by MTT assay; TBA method was used to determine mitochondrial lipid peroxidation. RESULT: Comprehensive analysis of multi-target results, the comprehensive activities of 40% ethanol elution and the middle layer were the highest. CONCLUSION: 40% ethanol elution and the middle layer were proportionally mixed as the effective components group of Xiaoxuming decoction. PMID- 22066458 TI - [Antiproliferative effects mechanism of beta-sitosterul in hepatoma HepG2 cells]. AB - OBJECTIVE: To study the antiproliferative effects of beta-sitosterul and its mechanism in hepatoma HepG2 cells. METHOD: Cell proliferation was assessed by MTT assay. Cell cycle distribution, apoptosis and mitochondrial membrane potential were measured by high content screening (HCS). The protein expression of caspase 3, caspase-8, caspase-9, Bcl-2, Bax, tBid and cytochrome c in the HepG2 cells were evaluated by Western Blots. RESULT: beta-Sitosterul exerted significant antiproliferative effects in HepG2 cells. Furthermore, beta-sitosterul also induced HepG2 cells apoptosis, lost mitochondrial membrane potential, activated caspase-3, caspase-8 and caspase-9, up-regulate Bax, tBid protein, down regulation Bcl-2 protein. However, beta-sitosterul had hardly any effects on QSG7701 cells. CONCLUSION: beta-Sitosterul exerted antiproliferative effects and induced HepG2 cells apoptosis via mitochondrial pathway and membrane death receptor pathway. PMID- 22066459 TI - [Role of vascular endothelial active facters in gas exchange impairment induced by tourniquet and the effect of shenmai injection]. AB - OBJECTIVE: To investigate the effect of Shenmai injection on vascular endothelial active facters nitric oxide (NO) and endothelin-1 (ET-1), and pulmonary gas exchange induced by tourniquet deflation in patients undergoing lower extremity surgery. METHOD: Twenty-six patients scheduled for unilateral lower extremity surgery were randomly divided into 2 groups: control group (group C, n = 14) and Shenmai injection group (group SM, n = 12). All the patients agreed to a combined spinal-epidural anesthesia at the L2-L3 interspace and a radial artery catheter was placed for sampling. Patients in group SM were injected Shenmai injection 0.6 mL x kg(-1) and physiological saline 100 mL, while patients in group C were injected equal volume of normal saline instead 15 min before tourniquet inflation. Blood samples which were used for blood gas analysis and measurement of nitric oxide (NO) and endothelin-1 (ET-1) were taken before tourniquet inflation (T0, baseline) and 30 min (T1), 2 h (T2), 6 h (T3), 24 h (T4) after tourniquet deflation. RESULT: Compared with the baseline values at T0, in group C at T3 P(a) O2 and the levels of NO were significantly decreased, while P(A-a) DO2 and the levels of ET-1 at T3 were significantly increased (P < 0.05 or P < 0.01), in group SM, the levels of NO at T3 were significantly decreased (P < 0.05). Compared with group C, the changes of P(a)O2, P(A-a) DO2, NO and ET-1 were significantly mitigated in group SM. CONCLUSION: The concentrations of NO and ET 1 is connected with the pulmonary gas exchange impairment induced by tourniquet application. Shenmai injection can improve the pulmonary gas exchange based on rising the level of NO, reducing the level of ET-1. PMID- 22066460 TI - CO2 sequestration through mineral carbonation of iron oxyhydroxides. AB - Carbon dioxide sequestration via the use of sulfide reductants and mineral carbonation of the iron oxyhydroxide polymorphs lepidocrocite, goethite, and akaganeite with supercritical CO(2) (scCO(2)) was investigated using in situ attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X ray diffraction (XRD), and transmission electron microscopy (TEM). The exposure of the different iron oxyhydroxides to aqueous sulfide in contact with scCO(2) at ~70-100 degrees C resulted in the partial transformation of the minerals to siderite (FeCO(3)) and sulfide phases such as pyrite (FeS(2)). The relative yield of siderite to iron sulfide bearing mineral product was a strong function of the initial sulfide concentration. The order of mineral reactivity with regard to the amount of siderite formation in the scCO(2)/sulfide environment for a specific reaction time was goethite < lepidocrocite <= akaganeite. Given the presence of goethite in sedimentary formations, this conversion reaction may have relevance to the subsurface sequestration and geologic storage of carbon dioxide. PMID- 22066461 TI - Smart high-kappa nanodielectrics using solid supported polyoxometalate-rich nanostructures. AB - Utilizing Langmuir-Blodgett deposition and scanning probe microscopy, we have investigated the extent to which cations alter the self-assembly processes of hybrid polyoxometalates (POMs) on surfaces. The well-defined 2D hexagonal nanostructures obtained were extensively characterized and their properties were studied, and this has revealed fascinating dielectric behavior and reversible capacitive properties. The nanostructures are extremely stable under ambient conditions, and yet exhibit fascinating self-patterning upon heating. These findings present POMs as effective smart nanodielectrics and open up a new field for future POM applications. PMID- 22066462 TI - Hydrogels containing rutin intended for cutaneous administration: efficacy in wound healing in rats. AB - OBJECTIVE: Development of a hydrogel containing rutin at 0.025% (w/w) and evaluation of its in vivo efficacy in cutaneous wound healing in rats. METHODS: Hydrogels were prepared using Carbopol Ultrez(r) 10 NF and an aqueous dispersion of rutin in polysorbate 80. Hydrogels were characterized by means of pH measurement, rheological and spreadability analysis and rutin content determination by liquid chromatography. The in vivo healing effect was evaluated through the regression of skin lesions in rats and by analysis of oxidative stress. RESULTS AND DISCUSSION: Hydrogels showed adequate pH values (5.50-6.50) and pseudoplastic non-Newtonian behavior. After 5 days of treatment of wounds, hydrogels containing rutin presented a higher decrease in the wound area compared to the control hydrogels. Analysis of the oxidative stress showed a decrease in lipid peroxidation and protein carbonyl content as well as an increase in catalase activity after the treatment with the hydrogel containing rutin. Furthermore, this treatment increased total protein levels. CONCLUSION: This study shows for the first time the feasibility of using dermatological formulations containing rutin to improve skin wound healing. PMID- 22066463 TI - Prediction and diagnosis of clinical outcomes affecting restoration margins. AB - The longevity of dental restorations is largely dependent on the continuity at the interface between the restorative material and adjacent tooth structure (the restoration margin). Clinical decisions on restoration repair or replacement are usually based upon the weakest point along that margin interface. Physical properties of a restorative material, such as polymerisation shrinkage, water sorption, solubility, elastic modulus and shear strength, all have an effect on stress distribution and can significantly affect margin integrity. This review will focus on two aspects of margin deterioration in the oral environment: the in vitro testing of margin seal using emersion techniques to simulate the oral environment and to predict clinical margin failure and the relationship between clinically observable microleakage and secondary caries. The many variables associated with in vitro testing of marginal leakage and the interpretation of the data are presented in detail. The most recent studies of marginal leakage mirror earlier methodology and lack validity and reliability. The lack of standardised testing procedures makes it impossible to compare studies or to predict the clinical performance of adhesive materials. Continual repeated in vitro studies contribute little to the science in this area. Clinical evidence is cited to refute earlier conclusions that clinical microleakage (penetrating margin discoloration) leads to caries development and is an indication for restoration replacement. Margin defects, without visible evidence of soft dentin on the wall or base of the defect, should be monitored, repaired or resealed, in lieu of total restoration replacement. PMID- 22066464 TI - Vertebrate ancient-long opsin has molecular properties intermediate between those of vertebrate and invertebrate visual pigments. AB - VA/VAL opsin is one of the four kinds of nonvisual opsins that are closely related to vertebrate visual pigments in the phylogenetic tree of opsins. Previous studies indicated that among these opsins, parapinopsin and pinopsin exhibit molecular properties similar to those of invertebrate bistable visual pigments and vertebrate visual pigments, respectively. Here we show that VA/VAL opsin exhibits molecular properties intermediate between those of parapinopsin and pinopsin. VAL opsin from Xenopus tropicalis was expressed in cultured cells, and the pigment with an absorption maximum at 501 nm was reconstituted by incubation with 11-cis-retinal. Light irradiation of this pigment caused cis-to trans isomerization of the chromophore to form a state having an absorption maximum in the visible region. This state has the ability to activate Gi and Gt types of G proteins. Therefore, the active state of VAL opsin is a visible light absorbing intermediate, which probably has a protonated retinylidene Schiff base as its chromophore, like the active state of parapinopsin. However, this state was apparently photoinsensitive and did not show reverse reaction to the original pigment, unlike the active state of parapinopsin, and instead similar to that of pinopsin. Furthermore, the Gi activation efficiency of VAL opsin was between those of pinopsin and parapinopsin. Thus, the molecular properties of VA/VAL opsin give insights into the mechanism of conversion of the molecular properties from invertebrate to vertebrate visual pigments. PMID- 22066465 TI - Urine metabolic signature of pancreatic ductal adenocarcinoma by (1)h nuclear magnetic resonance: identification, mapping, and evolution. AB - Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and is highly chemoresistant. Early detection is the only means to impact long-term survival, but screening methods are lacking. Given the complex and heterogeneous nature of pancreatic cancer, unbiased analytical methods such as metabolomics by nuclear magnetic resonance (NMR) spectroscopy show promise to identify disease-specific molecular fingerprints. NMR profiles constitute a fingerprint of the biofluid, reporting quantitatively on all detectable small biomolecules. NMR spectroscopy was applied to investigate the urine metabolome of PDAC patients (n = 33) and to detect altered metabolic profiles in comparison with healthy matched controls (n = 54). The spectral data were analyzed using multivariate statistical techniques. Statistically significant differences were found between urine metabolomic profiles of PDAC and control individuals (p < 10(-5)). Group discrimination was possible due to average concentration differences of several metabolite signals, pointing to a multimolecular signature of the disease. The robustness of the determined statistical model is confirmed by its predictive performance (sensitivity = 75.8%, specificity = 90.7%). Additionally, the method allowed for a neat separation between spectral profiles of individuals with intermediate and advanced pathologic staging, as well as for the discrimination of samples based on tumor localization. NMR spectroscopy analysis of urinary metabolic profiles proved successful in identifying a complex molecular signature of PDAC. Furthermore, results of a descriptive-level analysis show the possibility to follow disease evolution and to carry out tumor site mapping. Given the high reproducibility and the noninvasive nature of the analytical procedure, the described method bears potential to impact large-scale screening programs. PMID- 22066466 TI - High frequency region of the snore spectra carry important information on the disease of sleep apnoea. AB - Snoring is the most common symptom of obstructive sleep apnoea (OSA). Several researchers have reported differences between the power spectra of non-OSA and OSA snorers. The traditional approach over the years has been to record snore sounds at a bandwidth of < 5 kHz. Narrowing of the upper airways during OSA events and the resulting upward shift of snore frequencies also lend support to the idea of examining snore sounds beyond 5 kHz. In this paper, we compute the power spectra of snores in three different bands defined as: low-frequency band (LFB: < 5 kHz); middle-frequency band (MFB: 5-10 kHz) and high-frequency band (HFB: 10-20 kHz). We illustrate that there is a significant difference between non-OSA snorers (Apnoea Hypopnoea Index (AHI) < 10) and OSA snorers (AHI > 10) in the region > 5 kHz. We then develop a feature to diagnose OSA based on the spectral differences in the high frequency region and evaluate its performance on a database of 20 subjects. Our results strongly suggest that the high-frequency region of the snore sounds carry information, hitherto disregarded, on the disease of sleep apnoea. PMID- 22066467 TI - Perceptions of aggressive conflicts and others' distress in children with callous unemotional traits: 'I'll show you who's boss, even if you suffer and I get in trouble'. AB - BACKGROUND: Children with callous-unemotional (CU) traits may have a particularly malevolent view of social conflicts and a pervasive insensitivity to others' distress. The current study examined whether children with CU traits have unique expectations and values regarding the consequences of aggressive conflicts and a ubiquitous lack of concern for others' feelings independent of co-occurring aggression. METHODS: Participants were 96 (46 males, 50 females) children recruited from elementary schools within an urban city. Associations between CU traits and child reports of outcome expectancies/values following aggressive conflicts and facets of empathy were examined after controlling for aggression, academic abilities, and demographic covariates. RESULTS: Children with higher CU traits were less likely to expect that aggression would result in victim suffering and feelings of remorse. After controlling for co-occurring aggression, children with higher CU traits were more likely to expect that aggression would result in peer dominance, while children with higher levels of aggression were more likely to expect that attacking others would reduce their aversive behavior. Children with higher CU traits were less concerned that aggressive behavior would result in punishment, victim suffering, and feelings of remorse. Moreover, children with higher CU traits reported lower levels of empathetic concern and sadness in response to others' distress outside of aggressive conflicts. CONCLUSIONS: Children with CU traits tend to minimize the extent to which aggression causes victim suffering and openly acknowledge caring less about distress and suffering in others. They are less intimidated by the possibility of being punished for aggressive behavior and tend to view aggression as an effective means for dominating others. In sum, children with CU traits have a particularly malicious social schema that may be difficult to change using conventional treatment methods. PMID- 22066469 TI - Synthesis of substituted isoquinolines via Pd-catalyzed cross-coupling approaches. AB - Palladium complexes incorporating ligands based on a 1,3,5,7-tetramethyl-2,4,8 trioxa-6-phosphaadamantanyl scaffold were used to catalyze the arylation of ethyl cyanoacetate, malononitrile, and various ketones. The products from these reactions can be elaborated to substituted beta-arylethylamines and used in microwave-assisted Pictet-Spengler reactions. The protocol developed is suitable for the synthesis of libraries of substituted isoquinolines. PMID- 22066470 TI - High-frequency monitoring of the genetic diversity and the potential toxicity of a Microcystis aeruginosa bloom in a French shallow lake. AB - During cyanobacterial blooms, processes influencing the population dynamics of blooming species remain partially unexplained. To provide new information, we performed a high-frequency monitoring - every 2 days at six sampling points - of a Microcystis aeruginosa population blooming in a shallow lake. At each sampling date, there was no spatial heterogeneity in the ITS genotypic composition of the population and in the proportion of potentially microcystin- producing (mcyB+) cells, whereas high variations were recorded in cell abundances. In contrast, when looking at the temporal evolution of these parameters, the ITS genotypic composition of the population and in a lesser extent the percentage of mcyB+ cells displayed high variations during the growth phase of the bloom, but not during the plateau phase or the subsequent decline. This suggests that during the development of the bloom, there was no directional selection leading to the dominance of a restricted number of genotypes and that a balancing selection process permitted the maintenance of a high genetic diversity in the Microcystis population. Finally, no relationship was found between these variations occurring in the Microcystis population and those recorded for several environmental parameters, suggesting that many factors and processes interacting together might be involved in these variations. PMID- 22066468 TI - Mechanisms of altered redox regulation in neurodegenerative diseases--focus on S- glutathionylation. AB - SIGNIFICANCE: Neurodegenerative diseases are characterized by progressive loss of neurons. A common feature is oxidative stress, which arises when reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) exceed amounts required for normal redox signaling. An imbalance in ROS/RNS alters functionality of cysteines and perturbs thiol-disulfide homeostasis. Many cysteine modifications may occur, but reversible protein mixed disulfides with glutathione (GSH) likely represents the common steady-state derivative due to cellular abundance of GSH and ready conversion of cysteine-sulfenic acid and S-nitrosocysteine precursors to S glutathionylcysteine disulfides. Thus, S-glutathionylation acts in redox signal transduction and serves as a protective mechanism against irreversible cysteine oxidation. Reversal of protein-S-glutathionylation is catalyzed specifically by glutaredoxin which thereby plays a critical role in cellular regulation. This review highlights the role of oxidative modification of proteins, notably S glutathionylation, and alterations in thiol homeostatic enzyme activities in neurodegenerative diseases, providing insights for therapeutic intervention. RECENT ADVANCES: Recent studies show that dysregulation of redox signaling and sulfhydryl homeostasis likely contributes to onset/progression of neurodegeneration. Oxidative stress alters the thiol-disulfide status of key proteins that regulate the balance between cell survival and cell death. CRITICAL ISSUES: Much of the current information about redox modification of key enzymes and signaling intermediates has been gleaned from studies focused on oxidative stress situations other than the neurodegenerative diseases. FUTURE DIRECTIONS: The findings in other contexts are expected to apply to understanding neurodegenerative mechanisms. Identification of selectively glutathionylated proteins in a quantitative fashion will provide new insights about neuropathological consequences of this oxidative protein modification. PMID- 22066471 TI - Processing of CXCL12 by different osteoblast-secreted cathepsins. AB - Hematopoietic stem and progenitor cells (HSPCs) are known to reside in specialized niches at the endosteum in the trabecular bone. Osteoblasts are the major cell type of the endosteal niche. It is well established that secreted proteases are involved in cytokine-induced mobilization processes that release stem cell from their niches. However, migratory processes such as the regular trafficking of HSPCs between their niches and the periphery are not fully understood. In the current study we analyzed whether osteoblast-secreted cysteine cathepsins are able to reduce the direct interaction of HSPCs with bone-forming osteoblasts. Isolated human osteoblasts were shown to secrete proteolytically active cysteine cathepsins, such as cathepsins B, K, L, and X. All of these cathepsins were able to digest, although with different efficacy, the chemokine CXCL12, which is known to be important for retaining HSPCs in their niches. Of the 4 identified cathepsins, only cathepsin X was able to reduce binding of HSPCs to osteoblasts. Interestingly, nonactivated pro-cathepsin X and mature cathepsin X did not interfere with HSPC-osteoblast interactions. Only pro-cathepsin X treated with dithiothreitol, which unfolds but does not lead to full maturation of cathepsin X, significantly reduced HSPC adhesion to osteoblasts. These observations argue for a role of the accessible cathepsin X prodomain in diminishing cell binding. Our findings strongly suggest that the cysteine cathepsins B, K, and L constitutively secreted by osteoblasts are part of the fine-tuned regulation of CXCL12 in the bone marrow, whereas pro-cathepsin X with its prodomain can affect HSPC trafficking in the niche. PMID- 22066472 TI - Human heat shock protein (Hsp) 90 interferes with Neisseria meningitidis adhesin A (NadA)-mediated adhesion and invasion. AB - NadA (N eisseria meningitidisadhesin A), a meningococcal surface protein, mediates adhesion to and invasion of human cells, an activity in which host membrane proteins have been implicated. While investigating these host factors in human epithelial cells by affinity chromatography, we discovered an unanticipated interaction of NadA with heat shock protein (Hsp) 90, a molecular chaperone. The specific in vitro interaction of recombinant soluble NadA and Hsp90 was confirmed by co-immunoprecipitations, dot and far-Western blot. Intriguingly, ADP, but not ATP, was required for this association, and the Hsp90 inhibitor 17-AAG promoted complex formation. Hsp90 binding to an Escherichia coli strain used as carrier to express surface exposed NadA confirmed these results in live bacteria. We also examined RNA interference, plasmid-driven overexpression, addition of exogenous rHsp90 and 17-AAG inhibition in human epithelial cells to further elucidate the involvement of Hsp90 in NadA-mediated adhesion and invasion. Together, these data suggest an inverse correlation between the amount of host Hsp90 and the NadA adhesive/invasive phenotype. Confocal microscopy also demonstrated that meningococci interact with cellular Hsp90, a completely novel finding. Altogether our results show that variation of host Hsp90 expression or activity interferes with adhesive and invasive events driven by NadA. PMID- 22066473 TI - Impression techniques for multiple implants: a photoelastic analysis. Part I: comparison of three direct methods. AB - The purpose of this article was to compare through photoelastic analysis the stress distribution in 3 direct transfer techniques for implants with splinting. Three photoelastic resin blocks were made with 2 implants placed parallel to each other and 2 square transfer copings splinted. Both transfers were splinted with acrylic resin chemically activated in 3 different techniques: metallic sticks (T1), prefabricated acrylic bars (T2), or dental floss (T3). A circular polariscope was used, and the distortion energy (E) was calculated in 4 periods: 20 minutes and 3, 24, and 36 hours. Statistically significant differences were found among the 3 techniques (P < .05). The dental floss presented the greatest distortion energy values (T3 = 0.469 Kgf/mm(2)) and the metallic sticks the lowest values (T1 = 0.0 Kgf/mm(2)). Thus, the metallic sticks technique (T1) appears to be the most accurate protocol to be used for implant-supported prosthesis with multiple abutments. PMID- 22066474 TI - Ecological inference on bacterial succession using curve-based community fingerprint data analysis, demonstrated with rhizoremediation experiment. AB - Nucleic acid-based community fingerprinting methods are valuable tools in microbial ecology, as they offer rapid and robust means to compare large series of replicates and references. To avoid the time-consuming and potentially subjective procedures of peak-based examination, we assessed the possibility to apply direct curve-based data analysis on community fingerprints produced with bacterial length heterogeneity PCR (LH-PCR). The dataset comprised 180 profiles from a 21-week rhizoremediation greenhouse experiment with three treatments and 10 sampling times. Curve-based analysis quantified the progressive effect of the plant (Galega orientalis) and the reversible effect of the contaminant (fuel oil) on bacterial succession. The major observed community shifts were assigned to changes in plant biomass and contamination level by canonical correlation analysis. A novel method to extract relative abundance data from the fingerprint curves for Shannon diversity index revealed contamination to reversibly decrease community complexity. By cloning and sequencing the fragment lengths, recognized to change in time in the averaged LH-PCR profiles, we identified Aquabacterium (Betaproteobacteria) as the putative r-strategic fuel oil degrader, and K strategic Alphaproteobacteria growing in abundance later in succession. Curve based community fingerprint analysis can be used for rapid data prescreening or as a robust alternative for the more heavily parameterized peak-based analysis. PMID- 22066475 TI - Do patients gain weight after thyroidectomy for thyroid cancer? AB - BACKGROUND: Patients who undergo thyroidectomy often complain of weight gain, which they frequently attribute to inadequate thyroid hormone replacement. To assess the weight changes associated with thyroid hormone replacement or suppressive therapy after thyroidectomy, we measured the weights of patients before and after thyroidectomy and compared them to the weights of euthyroid patients with thyroid nodules who were being followed for many years. METHODS: The weights and heights of 67 women and 35 men who underwent total thyroidectomy for thyroid cancer were recorded before and for a mean of 8.3 years after thyroidectomy. All patients received either suppressive or replacement doses of levothyroxine. As a comparison group, 70 women and 22 men with goiter or thyroid nodules and were euthyroid had serial measurements of height and weight. They were followed for a mean of 7.6 years. The body mass index (BMI) and age-adjusted BMI percentiles were calculated. The weight, BMI, and BMI percentile changes were compared both unadjusted and adjusted for age, gender, thyrotropin (TSH) level, and duration between measurements. RESULTS: At baseline, patients with thyroid nodules were older (mean 50.4 years) than those with thyroid cancer (mean 45.8 years). There were no significant differences in baseline weight, BMI, or BMI percentile. The baseline TSH levels were lower for patients with thyroid cancer (mean 0.8 mIU/L) than for those with nodules (mean 1.8 mIU/L) (p=0.002). There were no significant differences between the changes in weight, BMI, or BMI percentile from the start to the completion of the study whether unadjusted or after adjustment for age, gender, TSH, and duration of follow-up. CONCLUSIONS: Despite the perception of many patients that their thyroidectomy and thyroid hormone replacement or suppressive therapy is responsible for their subsequent weight gain, there were no significant differences in weight gain over time in comparison to a control group of euthyroid patients with thyroid nodules or goiter. PMID- 22066477 TI - Similar clinical performance of a novel chimeric thyroid-stimulating hormone receptor bioassay and an automated thyroid-stimulating hormone receptor binding assay in Graves' disease. AB - BACKGROUND: Graves' disease (GD) is caused by the continuous stimulation of the thyroid gland by autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR). Two frequent assays for the measurement of TSHR autoantibodies (TSHRAb) were compared, one measuring stimulation of cyclic adenosine monophosphate (cAMP) production and one measuring inhibition of TSH binding, with regard to diagnostic accuracy for GD as well as whether there was an existence of their discordant results in patients with GD and painless thyroiditis (PT). METHODS: Using 106 sera from untreated GD and 80 sera from autoimmune PT, we compared the diagnostic performance of two TSHRAb assays that have been recently developed. The first one is a bioreporter assay using chimera TSHR (Mc-4), which detects a stimulation signal of cAMP level in cultured CHO cells (Mc4-TSAb assay). The second is a binding inhibition assay using the extracelluar domain of porcine TSHR and a monoclonal antibody (M22) closely mimicking the binding to TSH (M22-TRAb assay). In addition, we compared both assays by using eight sera from eight GD subjects becoming spontaneously hypothyroid due to appearance of thyroid blocking autoantibodies (TBAb) that were measured with inhibition rates of TSH stimulated cAMP in porcine cells. RESULTS: The Mc4-TSAb assay and the M22-TRAb assay were positive in 94.3% and 92.5% of the GD patients, respectively, whereas they were negative in 95.0% and 98.8% of the PT subjects. However, 10 of 106 GD sera (9.4%) showed discordant results. Six of 106 cases with untreated GD (5.7%) were Mc4-TSAb positive and M22-TRAb negative. In contrast, 4 of 106 sera (3.8%) were Mc4-TSAb negative but M22-TRAb positive. Two cases of untreated GD were negative for both Mc4-TSAb and M22-TRAb. In eight GD subjects with TBAb and hypothyroidism, the binding assay was highly positive, although Mc4-TSAb was negative. CONCLUSION: Similar and excellent performance was noted for the Mc4 TSAb and M22-TRAb assays in a large group of patients with GD. However, there was 9.4% discordance with regard to false negatives for GD and 3.8% discordance between the two tests with regard to false positives for PT. With regard to the relatively high rate of discordancy, a combination of both assays could reduce the presence of TSHRAb-seronegative GD. PMID- 22066476 TI - Review and hypothesis: does Graves' disease develop in non-human great apes? AB - BACKGROUND: Graves' disease, caused by stimulatory thyrotropin receptor (TSHR) autoantibodies, has not been observed in animals. In contrast, Hashimoto's thyroiditis develops in chickens, rats, mice, dogs, and marmosets. Attempts to induce an immune response in mice to the luteinizing-hormone receptor suggested that autoantigen glycosylation was one parameter involved in breaking self tolerance. Over evolution, TSHR glycosylation increased from three asparagine linked-glycans (N-glycans) in fish to six N-glycans in humans and great apes. All other placental mammals lack one N-glycan in the shed TSHR A-subunit, the primary Graves' disease autoantigen. We hypothesized that (a) lesser TSHR A-subunit glycosylation reduces immunogenicity, accounting for the absence of Graves' disease in most placental mammals; (b) due to human-like A-subunit glycosylation, Graves' disease might arise in great apes. Here, we review and analyze the literature on this subject and report the results of a survey of veterinarians at primate centers and zoos in North America. SUMMARY: Previous experimental data from induced TSHR antibodies in mice support a role for A-subunit glycosylation in breaking self-tolerance. An extensive search of the great-ape literature revealed five reports of noncongenital thyroid dysfunction, four with hypothyroidism and one with hyperthyroidism. The latter was a gorilla who was treated with anti-thyroid drugs but is now deceased. Neither serum nor thyroid tissue from this gorilla were available for analysis. The survey of veterinarians revealed that none of the 979 chimpanzees in primate research centers had a diagnosis of noncongenital thyroid dysfunction and among ~1100 great apes (gorillas, orangutans, and chimpanzees) in U.S. zoos, only three were hypothyroid, and none were hyperthyroid. CONCLUSIONS: Graves' disease appears to be either very rare or does not occur in great apes based on the literature and a survey of veterinarians. Although the available data do not advance our hypothesis, there is a paucity of information regarding thyroid function tests and thyroid autoantibodies in the great apes In addition, these primates may be protected against TSHR autoimmunity by the absence of genetic polymorphisms and putative environmental triggers. Finally, larger numbers of great apes need to be followed, and tests of thyroid function and thyroid autoantibodies be performed, to confirm that spontaneous Graves' disease is restricted to humans. PMID- 22066478 TI - Identification of continuity of transected nerve on sonography after neck dissection: direct sign of traumatic neuroma. AB - BACKGROUND: Traumatic neuroma can be confused with a metastatic lymph node after neck dissection for malignancy, thereby increasing patient anxiety and necessitating fine needle aspiration (FNA). To date, however, there have been no reports showing a direct ultrasonographic (US) sign of traumatic neuroma that could help distinguish it from a metastatic lymph node after neck dissection. Here, we describe a patient with traumatic neuroma who showed a direct US sign after total thyroidectomy with modified radical neck dissection (MRND). SUMMARY: A 61-year-old man who had undergone total thyroidectomy with bilateral MRND for papillary thyroid carcinoma was found to have an oval-shaped nodule in his right lateral neck by US examination, which was first suspected of being a metastatic lymph node. However, when the position of the US transducer was changed to the oblique plane, a thin, cord-like, hypoechoic structure was found to be connected to the nodule. This structure passed between the longus capitis and scalenus medius muscles in an upward direction, and was ultimately located in the groove of the right transverse process of the C4 vertebra. Based on this anatomic relation, we concluded that the nodule was a traumatic neuroma and did not perform an unnecessary FNA. CONCLUSIONS: The detection of a mass in the line of the transected nerve may be a direct US indication of traumatic neuroma after neck dissection. PMID- 22066479 TI - Delta-like 4/Notch pathway is differentially regulated in benign and malignant thyroid tissues. AB - BACKGROUND: Angiogenesis plays an essential role in embryonic and tumoral developments. Vascular endothelial growth factor (VEGF), one of the best known proangiogenic factors, is increased in thyroid cancers, especially in papillary carcinomas (PC). However, other regulating mechanisms refine VEGF-induced cellular changes, such as the Notch family of ligands and receptors. Their role has not yet been investigated in the thyroid. The purpose of our study was to analyze the expression of Notch1, Notch4, and Delta-like 4 (DLL4) in benign and malignant thyroid lesions. METHODS: The expression of Notch1, Notch4, and DLL4 was analyzed by immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and Western-blot in normal thyroids (NTs), hyperplasic thyroids from patients with Graves' disease (GD), microcarcinomas, PC, and follicular carcinomas. RESULTS: The immunohistochemical expression of Notch1, Notch4, and DLL4 was highly variable in thyrocytes from NTs and GD. In contrast, the staining in tumors was homogeneous and often intense. The increased expression of Notch1, Notch4, and DLL4 in carcinomas compared with the neighboring normal tissue was confirmed by qRT-PCR and Western-blot. However, only capillary endothelial cells from GD samples were positive for DLL4, the expression being restricted to large vessels in carcinomas and NTs. CONCLUSIONS: The detection of Notch1, Notch4, and DLL4 in thyrocytes and their regulation in various pathologies suggest that this pathway may play a role in thyroid carcinogenesis and angiogenesis. PMID- 22066480 TI - Graves'-like orbitopathy in a patient with chronic autoimmune pancreatitis. AB - BACKGROUND: Graves' orbitopathy is an inflammatory orbital disease that represents the commonest extrathyroidal manifestation of Graves' disease. Autoimmune pancreatitis (AIP) is a rare inflammatory disease characterized by prominent lymphocytic infiltration and fibrosis of the pancreas causing organ dysfunction. SUMMARY: This report provides the first clinical description of severe Graves'-like orbitopathy occurring in association with AIP. Although there was no clear evidence of autoimmune thyroid disease or dysfunction in our patient, the clinical course of his orbitopathy was related to that of AIP, the relapses of orbital inflammation being temporally coincident. CONCLUSIONS: Our data suggest that shared autoantigens between the pancreas and the orbit might be responsible for the unusual disorder observed in our patient. PMID- 22066481 TI - Meningocele due to closed spina bifida mimicking a metastasis of papillary thyroid carcinoma on whole body radioactive iodine scan. PMID- 22066482 TI - Weight changes in euthyroid patients undergoing thyroidectomy. AB - BACKGROUND: Thyroidectomized patients frequently report weight gain resistant to weight loss efforts, identifying their thyroidectomy as the event precipitating subsequent weight gain. We wished to determine whether recently thyroidectomized euthyroid patients gained more weight over 1 year than matched euthyroid patients with preexisting hypothyroidism. METHODS: We performed a retrospective chart review of subjects receiving medical care at an academic medical center. One hundred twenty patients had their weight and thyroid status documented after thyroidectomy and achievement of euthyroidism on thyroid hormone replacement, and one year later. Three additional groups of 120 patients with preexisting hypothyroidism, no thyroid disease, and thyroid cancer were matched for age, gender, menopausal status, height, and weight. Anthropometric data were documented at two time points 1 year apart. We compared the weight changes and body mass index changes occurring over a 1-year period in the four groups. RESULTS: Patients with recent postsurgical hypothyroidism gained 3.1 kg during the year, whereas matched patients with preexisting hypothyroidism gained 2.2 kg. The patients without thyroid disease and those with iatrogenic hyperthyroidism gained 1.3 and 1.2 kg, respectively. The weight gain in the thyroidectomized group was significantly greater than that in the matched hypothyroid group (p value 0.004), the group without thyroid disease (p-value 0.001), and the patients with iatrogenic hyperthyroidism (p-value 0.001). Within the thyroidectomized group, the weight gain in menopausal women was greater than in either premenopausal women (4.4 vs. 2.3 kg, p-value 0.007) or men (4.4 vs. 2.5 kg, p value 0.013). CONCLUSION: Patients who had undergone thyroidectomy in the previous year did, in fact, gain more weight than their matched counterparts with preexisting hypothyroidism. In addition, all patients with hypothyroidism, even though treated to achieve euthyroidism, experienced more weight gain than both subjects without hypothyroidism and subjects with iatrogenic hyperthyroidism. The greatest weight gain in the thyroidectomized group was in menopausal women. These data raise the question of an unidentified factor related to taking thyroid hormone replacement that is associated with weight gain, with an additional intriguing effect of thyroidectomy itself. Menopausal status confers additional risk. These groups should be targeted for diligent weight loss efforts. PMID- 22066483 TI - Characterization of Loeffler eosinophilic myocarditis by means of real time three dimensional contrast-enhanced echocardiography. AB - Loeffler endocarditis is a rare myocardial disease often due to eosinophil leukemia or idiopathic hypereosinophilic syndrome. Degranulation of eosinophils within the eosinophil infiltrated myocardium is associated with myocardial necrosis due to the release of toxic cationic proteins, and with mural thrombi formation, which can occur anywhere in the ventricles. Thrombus formed on denuded myocardium is replaced by fibrosis as the final pathological stage of the disease, eventually leading to restrictive cardiomyopathy. We describe a multimodality imaging approach to the diagnosis and follow-up evaluation of Loeffler disease complicated by thrombus formation and neoangiogenesis of LV apex. PMID- 22066484 TI - Together yes, but not coupled: new insights into the roles of RAD51 and DMC1 in plant meiotic recombination. AB - The eukaryotic recombinases RAD51 and DMC1 are essential for DNA strand-exchange between homologous chromosomes during meiosis. RAD51 is also expressed during mitosis, and mediates homologous recombination (HR) between sister chromatids. It has been suggested that DMC1 might be involved in the switch from intersister chromatid recombination in somatic cells to interhomolog meiotic recombination. At meiosis, the Arabidopsis Atrad51 null mutant fails to synapse and has extensive chromosome fragmentation. The Atdmc1 null mutant is also asynaptic, but in this case chromosome fragmentation is absent. Thus in plants, AtDMC1 appears to be indispensable for interhomolog homologous recombination, whereas AtRAD51 seems to be more involved in intersister recombination. In this work, we have studied a new AtRAD51 knock-down mutant, Atrad51-2, which expresses only a small quantity of RAD51 protein. Atrad51-2 mutant plants are sterile and hypersensitive to DNA double-strand break induction, but their vegetative development is apparently normal. The meiotic phenotype of the mutant consists of partial synapsis, an elevated frequency of univalents, a low incidence of chromosome fragmentation and multivalent chromosome associations. Surprisingly, non homologous chromosomes are involved in 51% of bivalents. The depletion of AtDMC1 in the Atrad51-2 background results in the loss of bivalents and in an increase of chromosome fragmentation. Our results suggest that a critical level of AtRAD51 is required to ensure the fidelity of HR during interchromosomal exchanges. Assuming the existence of asymmetrical DNA strand invasion during the initial steps of recombination, we have developed a working model in which the initial step of strand invasion is mediated by AtDMC1, with AtRAD51 required to check the fidelity of this process. PMID- 22066485 TI - Assessment of vaccination by a phase I Coxiella burnetii-inactivated vaccine in goat herds in clinical Q fever situation. AB - A study was carried out to assess the efficacy of vaccination, using a phase I Coxiella burnetii-inactivated vaccine (Coxevac(r); CEVA), within three goat herds experiencing Q fever abortions waves. The stratification of the population (n = 905) was based on parity and on infection status related to both serological and qPCR vaginal shedding results. Control (n = 443) and vaccinated (n = 462) groups were established in each farm. Vaccination was administered to does before mating and to kids after active immunity acquisition (at least 3-4 months old). The vaccine effectiveness was analyzed at subsequent farrowing on both clinical incidence and vaginal shedding at the delivery day. Among the 231 animals considered as susceptible, that is, seronegative nonshedders, about 90% were infected whatever the group, showing that vaccination did not prevent infection under high infection exposure. Fortunately, vaccination induced an overall decrease in shedding levels. A significant average difference between groups was estimated to 1.16 log(10) bacteria per swab for primiparous and even higher (1.81 log(10)) for initially susceptible ones. Thus, in a clinical context, vaccination should be implemented first in renewal animals. Indeed, young animals are those which best respond to vaccination by significantly reducing C. burnetii burden and, conversely, which excrete bacteria most massively if not vaccinated. PMID- 22066486 TI - Clinical and economic analysis of rescue intracytoplasmic sperm injection cycles. AB - OBJECTIVE: To identify clinical and embryological factors that may predict success in rescue intracytoplasmic sperm injection (ICSI) cycles (after total fertilization failure has occurred) and to evaluate the cost effectiveness of rescue ICSI strategy. Additionally, follow-up of 20 rescue ICSI pregnancies is reported. DESIGN: Retrospective analysis of total fertilization failure cycles. SETTING: University-based tertiary medical center. MATERIAL AND METHODS: In total, 92 patients who had undergone conventional in-vitro fertilization (IVF) cycles with total fertilization failure were included. The patients were divided into two subgroups: those who conceived through rescue ICSI and those who did not. RESULTS: The pregnant members of the rescue ICSI subgroup were found to be significantly younger (32.9 +/- 4.2 vs. 36.3 +/- 4.5, respectively, p = 0.0035,) and to have better-quality embryos than those who did not conceive (cumulative embryo score: 38.3 +/- 20.4 vs. 29.3 +/- 14.7, p = 0.025). Cost effectiveness analysis showed 25% reduction in the cost per live birth when rescue ICSI is compared to cycle cancellation approach. The pregnancies follow-up did not show adverse perinatal outcome. CONCLUSIONS: Rescue ICSI is an option for salvaging IVF cycles complicated by total fertilization failure. Success in rescue ICSI was found to be associated with younger age and higher quality of embryos. Furthermore, the cost effectiveness of rescue ICSI in terms of total fertilization failure was found to be worthwhile. PMID- 22066487 TI - Predictors of postoperative sore throat in intubated children. AB - BACKGROUND: The incidence of postoperative sore throat (POST) following intubation is not well defined in the pediatric population. The etiology is multifactorial and includes impairment of subglottic mucosal perfusion and edema as a result of the pressures exerted by cuffed or uncuffed tubes. AIM: To determine the incidence of, and risk factors for, POST in intubated children undergoing elective day-case surgery. METHODS: Five hundred patients aged 3-16 years were studied prospectively. Endotracheal tube (ETT) choice (cuffed or uncuffed) was left to the anesthetist. The cuff was inflated either until loss of audible leak or to a determined pressure using a cuff manometer. The research team then measured the cuff pressure (CP). POST incidence and intensity was determined by interviewing patients prior to discharge from the same day procedure unit. Chi-square testing and stepwise logistic regression were used to determine the predictors of POST. RESULTS: Of the 111 (22%) children developed a sore throat, 19 (3.8%) a sore neck, and 5 (1%) a sore jaw. 19% of patients with cuffed ETTs complained of sore throat compared with 37% of those intubated with an uncuffed ETT. The incidence of POST increased with CP; 0-10% at 0 cmH(2)O, 4% at 11-20 cmH(2)O, 20% at 21-30 cmH(2)O, 68% at CP 31-40 cmH(2)O, and 96% at CP >40 cmH(2)O. The ETT CP and use of uncuffed ETTs were univariate predictors of POST. CONCLUSIONS: Children intubated with uncuffed ETTs are more likely to have POST. ETT CP is positively correlated with the incidence of POST. When using cuffed ETTs, CP should be routinely measured intraoperatively. PMID- 22066488 TI - Genome-wide screening and identification of antigens for rickettsial vaccine development. AB - The capacity to identify immunogens for vaccine development by genome-wide screening has been markedly enhanced by the availability of microbial genome sequences coupled to proteomic and bioinformatic analysis. Critical to this approach is in vivo testing in the context of a natural host-pathogen relationship, one that includes genetic diversity in the host as well as among pathogen strains. We aggregate the results of three independent genome-wide screens using in vivo immunization and protection against Anaplasma marginale as a model for discovery of vaccine antigens for rickettsial pathogens. In silico analysis identified 62 outer membrane proteins (Omp) from the 949 predicted proteins in the A. marginale genome. These 62 Omps were reduced to 10 vaccine candidates by two independent genome-wide screens using IgG2 from vaccinates protected from challenge following vaccination with outer membranes (screen 1) or bacterial surface complexes (screen 2). Omps with broadly conserved epitopes were identified by immunization with a live heterologous vaccine, A. marginale ssp. centrale (screen 3), reducing the candidates to three. The genome-wide screens identified Omps that have orthologs broadly conserved among rickettsial pathogens, highlighted the importance of identifying immunologically subdominant antigens, and supported the use of reverse vaccinology approaches in vaccine development for rickettsial diseases. PMID- 22066489 TI - Erythromycin enhances abomasal emptying in healthy unweaned lambs as shown by acetaminophen absorption test. PMID- 22066490 TI - Rat bite fever: fever, arthritis, and rash in a 4-year-old boy. AB - Rat bite fever is a rare but potentially fatal Gram-negative infection that predominantly affects populations with exposure to rats, notably children. The clinical presentation is nonspecific and requires a high threshold of suspicion to elicit a history of rat exposure. We report here a case of a child whose diagnosis was made retrospectively but with good outcome. PMID- 22066491 TI - Family-centred care: a qualitative study of Chinese and South Asian immigrant parents' experiences of care in paediatric oncology. AB - BACKGROUND: Over the past two decades, there is increasing emphasis being placed upon providing family-centred care (FCC) in paediatric oncology settings. However, there is a lack of knowledge of FCC in paediatric oncology from the perspectives of immigrant parents. The purpose of this paper is to describe Chinese and South Asian immigrant parents' experiences of FCC in paediatric oncology settings in Canada. METHODS: This study adopted a constructivist grounded theory approach. Fifty first generation Chinese and South Asian parents of children with cancer who were at least 6 months post-diagnosis were recruited from six Canadian paediatric oncology centres. Interviews were conducted in English, Cantonese, Mandarin, Urdu, Punjabi or Hindi, and transcribed into English. Analysis involved line-by-line, focused and theoretical coding, and the use of the constant comparison method. RESULTS: Findings indicated that overall parents were highly satisfied with the care and services they received, and their experiences were reflective of the key elements of FCC. However, there were some areas of concern identified by participants: parents not perceiving themselves as a member of the medical team; inconsistency in the quality and co-ordination of services among healthcare providers; disrespectful and mechanical manner of a few healthcare providers; and parents' discomfort with healthcare providers communicating sensitive health-related information directly with their child. CONCLUSIONS: In order to successfully provide family-centred services to immigrant parents of children with cancer, better communication of the elements of FCC between healthcare staff and families is needed to negotiate a clear role for the parents as partners of the healthcare team. Moreover, a better understanding of how family relationships are structured in immigrant families will assist healthcare providers to balance the best interests of the child with that of the family as a unit. PMID- 22066492 TI - Rapid, label-free, electrical whole blood bioassay based on nanobiosensor systems. AB - Biomarker detection based on nanowire biosensors has attracted a significant amount of research effort in recent years. However, only very limited research work has been directed toward biomarker detection directly from physiological fluids mainly because of challenges caused by the complexity of media. This limitation significantly reduces the practical impact generated by the aforementioned nanobiosensors. In this study, we demonstrate an In(2)O(3) nanowire-based biosensing system that is capable of performing rapid, label-free, electrical detection of cancer biomarkers directly from human whole blood collected by a finger prick. Passivating the nanowire surface successfully blocked the signal induced by nonspecific binding when performing active measurement in whole blood. Passivated devices showed markedly smaller signals induced by nonspecific binding of proteins and other biomaterials in serum and higher sensitivity to target biomarkers than bare devices. The detection limit of passivated sensors for biomarkers in whole blood was similar to the detection limit for the same analyte in purified buffer solutions at the same ionic strength, suggesting minimal decrease in device performance in the complex media. We then demonstrated detection of multiple cancer biomarkers with high reliability at clinically meaningful concentrations from whole blood collected by a finger prick using this sensing system. PMID- 22066493 TI - Ditetraalkylammonium amino acid ionic liquids as CO2 absorbents of high capacity. AB - By grafting butyl or ethyl onto tetramethylethylenediamine, quaternary ammonium salts with two positive charge centers were formed at the first step. Metathesis with Ag(2)O followed. Through neutralization with glycine, l-alanine, or valine, a series of new ditetraalkylammonium amino acid ionic liquids (DILs) for CO(2) capture were generated. The structures of DILs, as shown in Figure 1, were verified by using (1)H NMR and EA. These DILs were found to be of quite high viscosity which militated against their industrial application in CO(2) removal. Drawing on the experience of mixed amines' aqueous solutions, these DILs were blended with water or N-methyldiethanolamine (MDEA) aqueous solutions to act as special absorbents of CO(2). Using a Double-Tank Absorption System, the absorption performance of these DIL solutions was investigated in detail. The experimental results indicated that among the three aqueous solutions of DILs (20%, 40%, and 80 wt %), the solution of 40% DIL had a higher absorption rate of CO(2) than the other two, demonstrating the different effects of concentration and viscosity on the absorption. The solution of 40% DIL or the 15% DIL + 15% MDEA had much higher capacity for CO(2) than the corresponding monocation tetraalkylammonium AAILs, due to the special structure of the dication which could influence the solubility of CO(2) in the aqueous solution. PMID- 22066494 TI - Investigating the role of metal chelation in HIV-1 integrase strand transfer inhibitors. AB - HIV-1 integrase (IN) has been validated as an attractive target for the treatment of HIV/AIDS. Several studies have confirmed that the metal binding function is a crucial feature in many of the reported IN inhibitors. To provide new insights on the metal chelating mechanism of IN inhibitors, we prepared a series of metal complexes of two ligands (HL1 and HL2), designed as representative models of the clinically used compounds raltegravir and elvitegravir. Potentiometric measurements were conducted for HL2 in the presence of Mg(II), Mn(II), Co(II), and Zn(II) in order to delineate a metal speciation model. We also determined the X-ray structures of both of the ligands and of three representative metal complexes. Our results support the hypothesis that several selective strand transfer inhibitors preferentially chelate one cation in solution and that the metal complexes can interact with the active site of the enzyme. PMID- 22066495 TI - Heme ligand identification and redox properties of the cytochrome c synthetase, CcmF. AB - Cytochrome c maturation in many bacteria, archaea, and plant mitochondria involves the integral membrane protein CcmF, which is thought to function as a cytochrome c synthetase by facilitating the final covalent attachment of heme to the apocytochrome c. We previously reported that the E. coli CcmF protein contains a b-type heme that is stably and stoichiometrically associated with the protein and is not the heme attached to apocytochrome c. Here, we show that mutation of either of two conserved transmembrane histidines (His261 or His491) impairs stoichiometric b-heme binding in CcmF and results in spectral perturbations in the remaining heme. Exogeneous imidazole is able to correct cytochrome c maturation for His261 and His491 substitutions with small side chains (Ala or Gly), suggesting that a "cavity" is formed in these CcmF mutants in which imidazole binds and acts as a functional ligand to the b-heme. The results of resonance Raman spectroscopy on wild-type CcmF are consistent with a hexacoordinate low-spin b-heme with at least one endogeneous axial His ligand. Analysis of purified recombinant CcmF proteins from diverse prokaryotes reveals that the b-heme in CcmF is widely conserved. We have also determined the reduction potential of the CcmF b-heme (E(m,7) = -147 mV). We discuss these results in the context of CcmF structure and functions as a heme reductase and cytochrome c synthetase. PMID- 22066496 TI - Artificial tactile sensing approach in aortic-repair-laparoscopy: aorta cross clamping during surgery. AB - Abdominal aortic aneurysm is one of the most common diseases of the vascular system for which the most definitive treatment is surgery. Laparoscopy is a primary method of minimally invasive surgery that could be useful in aortic repair surgeries. Although this method of surgery has significant advantages, the difficulty of exactly distinguishing the aorta from its surrounding tissues is its main drawback; this can cause many problems during the aorta cross clamping process. One of the most important limitations is that it is a time-consuming process; aorta cross clamping leads to increases in surgery duration. Artificial tactile sensing is an innovative technology aiming to make tactile data more available for surgeons, especially in situations where developments in technology make the surgeons less efficient. In this paper, considering the present problems during aortic repair laparoscopy, applicability of a novel tactile robotic system capable of cross clamping an artery during laparoscopy was evaluated. Having considered a small, 5-degree-of-planar-freedom robot and imitated surgeon's palpation using software, the path followed by the tip of the new tactile robotic system was extracted. It is shown that this new tactile robotic system is well capable of dissecting an artery from its adjacent tissues in a short time with an acceptable accuracy. The functional principles of the tactile robotic system capable of cross clamping the aorta during laparoscopy will also be presented. PMID- 22066497 TI - An epidemiological study of ADHD symptoms among young persons and the relationship with cigarette smoking, alcohol consumption and illicit drug use. AB - BACKGROUND: This study investigates the relationship between attention deficit hyperactivity disorder (ADHD) symptoms and cigarette smoking, alcohol use and illicit drug use. METHOD: The participants were 10,987 pupils in the final three years of their compulsory education in Iceland (ages 14-16 years). The participants completed questionnaires in class relating to anxiety, depression and antiestablishment attitudes, ADHD symptoms, smoking, alcohol consumption and illicit drug use. RESULTS: Of the total sample, 5.4% met screening criteria for ADHD. Smoking, alcohol and illicit drug use were significantly related to ADHD symptoms. In addition, the number of different illicit drugs consumed was significantly higher among the ADHD symptomatic than the nonsymptomatic participants, including the illicit use of sedatives. The main distinguishing illicit drug substances were lysergic acid diethylamide (odds ratio or OR = 8.0), cocaine (OR = 7.5), mushrooms (OR = 7.1) and amphetamines (OR = 6.5). Logistic multiple regressions showed that after controlling for gender and school grade, ADHD symptoms predicted smoking, alcohol use and illicit drug use independent of anxiety, depression and antiestablishment attitudes. In addition, poly-substance use was linearly and incrementally related to ADHD symptoms with a large effect size. CONCLUSIONS: The findings underscore the vulnerability of young persons with ADHD symptoms to smoking, alcohol and illicit drug use, possibly as a means of self-medication, and emphasize a need for early identification and treatment to reduce the risk of escalation. PMID- 22066498 TI - Formation routes of interstellar glycine involving carboxylic acids: possible favoritism between gas and solid phase. AB - Despite the extensive search for glycine (NH2CH2COOH) and other amino acids in molecular clouds associated with star-forming regions, only upper limits have been derived from radio observations. Nevertheless, two of glycine's precursors, formic acid and acetic acid, have been abundantly detected. Although both precursors may lead to glycine formation, the efficiency of reaction depends on their abundance and survival in the presence of a radiation field. These facts could promote some favoritism in the reaction pathways in the gas phase and solid phase (ice). Glycine and these two simplest carboxylic acids are found in many meteorites. Recently, glycine was also observed in cometary samples returned by the Stardust space probe. The goal of this work was to perform theoretical calculations for several interstellar reactions involving the simplest carboxylic acids as well as the carboxyl radical (COOH) in both gas and solid (ice) phase to understand which reactions could be the most favorable to produce glycine in interstellar regions fully illuminated by soft X-rays and UV, such as star forming regions. The calculations were performed at four different levels for the gas phase (B3LYP/6-31G*, B3LYP/6-31++G**, MP2/6-31G*, and MP2/6-31++G**) and at MP2/6-31++G** level for the solid phase (ice). The current two-body reactions (thermochemical calculation) were combined with previous experimental data on the photodissociation of carboxylic acids to promote possible favoritism for glycine formation in the scenario involving formic and acetic acid in both gas and solid phase. Given that formic acid is destroyed more in the gas phase by soft X-rays than acetic acid is, we suggest that in the gas phase the most favorable reactions are acetic acid with NH or NH2OH. Another possible reaction involves NH2CH2 and COOH, one of the most-produced radicals from the photodissociation of acetic acid. In the solid phase, we suggest that the reactions of formic acid with NH2CH or NH2CH2OH are the most favorable from the thermochemical point of view. PMID- 22066500 TI - Analogs of Grubbs' second generation catalyst with hydrophilic phosphine ligands: phase transfer activation of ring closing alkene metathesis. AB - Analogs of Grubbs' second generation catalyst with hydrophilic phosphine ligands are synthesized, and those with Cy(2)PCH(2)CH(2)N(CH(3))(3)(+) Cl(-) and Cy(2)PCHCH(2)CH(2)N(CH(3))(2)(+)CH(2)CH(2) Cl(-) give much faster ring closing metatheses under CH(2)Cl(2)/aqueous or CH(2)Cl(2)/aqueous HCl biphasic as opposed to CH(2)Cl(2) monophasic conditions. This is attributed to rapid phase transfer of the dissociated ligand to the aqueous phase, where under acidic conditions it is protonated. PMID- 22066499 TI - Bacteria associated with skeletal tissue growth anomalies in the coral Platygyra carnosus. AB - Scleractinian corals with growth anomalies, often referred to as 'tumors', have been reported globally. A recent survey of Hong Kong waters showed that > 60% of Platygyra carnosus colonies developed tumors. Here we report for the first time, the bacterial community associated with tumors in P. carnosus over different seasons and locations in Hoi Ha Wan Marine Park and Port Shelter. Culture-based methods for strain isolation and molecular techniques of 16S rRNA analysis for strain identification were used, as well as the culture-independent technique terminal-restriction fragment length polymorphism. We tested the hypothesis that the community composition would be considerably different between healthy and tumor corals and aimed to investigate whether potential differences because of tumors would override the seasonal and spatial influences. Our analysis detected only minor differences between the communities associated with the healthy and tumor corals, indicating that tumors are not associated with major changes in the bacterial community structure. In contrast, community structure was strongly influenced by the location and season, with greater Alphaproteobacteria diversity in the winter than in the summer. This study demonstrated that the coral associated bacterial community composition was more related to environmental variables (i.e. season and location) than to disease (i.e. tumor). PMID- 22066501 TI - Effects of long-term fertilization of forest soils on potential nitrification and on the abundance and community structure of ammonia oxidizers and nitrite oxidizers. AB - Forest fertilization in British Columbia is increasing, to alleviate timber shortfalls resulting from the mountain pine beetle epidemic. However, fertilization effects on soil microbial communities, and consequently ecosystem processes, are poorly understood. Fertilization has contrasting effects on ammonia-oxidizing bacteria and archaea (AOB and AOA) in grassland and agricultural ecosystems, but there are no studies on AOB and AOA in forests. We assessed the effect of periodic (6-yearly application 200 kg N ha-1) and annual (c. 75 kg N ha-1) fertilization of lodgepole pine and spruce stands at five long term maximum productivity sites on potential nitrification (PN), and the abundance and diversity of AOB, AOA and Nitrobacter and Nitrospira-like nitrite oxidizing bacteria (NOB). Fertilization increased AOB and Nitrobacter-like NOB abundances at some sites, but did not influence AOA and Nitrospira-like NOB abundances. AOB and Nitrobacter-like NOB abundances were correlated with PN and soil nitrate concentration; no such correlations were observed for AOA and Nitrospira-like NOB. Autotrophic nitrification dominated (55-97%) in these forests and PN rates were enhanced for up to 2 years following periodic fertilization. More changes in community composition between control and fertilized plots were observed for AOB and Nitrobacter-like NOB than AOA. We conclude that fertilization causes rapid shifts in the structure of AOB and Nitrobacter-like NOB communities that dominate nitrification in these forests. PMID- 22066502 TI - Pediatric psychiatry, and a note on malpractice. PMID- 22066503 TI - This issue: treatment of child and adolescent mental health. PMID- 22066504 TI - A 16-year-old girl with leg pain and swelling. PMID- 22066505 TI - Management of anxiety disorders in the pediatric primary care setting. PMID- 22066506 TI - Treatment of depression in children and adolescents. PMID- 22066507 TI - Treatment of attention-deficit/hyperactivity disorder. PMID- 22066508 TI - Management of disruptive behavior disorders. PMID- 22066509 TI - Evidence-based treatment approach to autism spectrum disorders. PMID- 22066510 TI - Human umbilical cord blood-derived mesenchymal stem cells undergo cellular senescence in response to oxidative stress. AB - Since human mesenchymal stem cells (MSCs) are therapeutically attractive for tissue regeneration and repair, we examined the physiological responses of human umbilical cord blood-derived MSCs (hUCB-MSCs) to genotoxic stress. We found that that sublethal doses of reactive oxygen species (ROS) and ionizing radiation cause DNA damage and reduce DNA synthesis and cell proliferation in hUCB-MSCs, resulting in cellular senescence. In contrast, these physiological changes were limited in human fibroblast and cancer cells. Our data show that reduced activities of antioxidant enzymes, which may occur due to low gene expression levels, cause hUCB-MSCs to undergo cellular senescence in response to oxidative stress and ionizing radiation. Resistance of hUCB-MSCs to oxidative stresses was restored by increasing the intracellular antioxidant activity in hUCB-MSCs via exogenous addition of antioxidants. Therefore, the proliferation and fate of hUCB MSCs can be controlled by exposure to oxidative stresses. PMID- 22066511 TI - Oncological outcome after laparoscopic abdominoperineal excision of the rectum. AB - AIM: Abdominoperineal excision of the rectum (APER) for cancer has been associated with higher circumferential resection margin (CRM) involvement and failure of local disease control. The aim of this study was to investigate whether the introduction of laparoscopic APER altered the incidence of CRM involvement. METHOD: Consecutive patients undergoing open or laparoscopic APER for adenocarcinomas of the rectum were studied. Patient demographics, preoperative staging, neoadjuvant treatment, operative findings, length of stay and pathological details were collected from operative and radiology databases and compared. RESULTS: There were 16 laparoscopic and 25 open APER performed over a 3-year period. Neoadjuvant therapy was given to 43.8% (7/16) of the laparoscopic group and 56.0% (14/25) of the open group. Complete laparoscopic resection was possible in 14 (87.5%) of 16 patients. The median harvested number of nodes was 14 (4-33) in both groups. The median length of stay was 7 (3-13) and 15 (9-40) days in the laparoscopic and open groups (P < 0.001). The CRM was clear in all cases. There was no local recurrence in either group at a median follow-up of 23 months. There were no in-hospital deaths and no significant differences in overall survival. There were no significant differences in preoperative or postoperative histopathological T stage between the two groups (P = 0.057 and P = 0.121). CONCLUSION: Laparoscopic APER for selected rectal cancers can achieve comparable oncological outcome to open surgery but is associated with a much shorter length of stay. Patient and tumour characteristics must be taken into consideration when deciding on a laparoscopic approach for low rectal cancer. PMID- 22066512 TI - Esthetics in implant-supported prostheses: a literature review. AB - Esthetics is important for success of implant-supported prostheses. This study aimed to review esthetics concepts for implant treatment. Research in the PubMed database included studies published from 1995 to 2010 with the keywords implant esthetics, implant-supported prostheses, and esthetics. Forty-five studies were evaluated regarding the presurgical planning, surgical phase, and temporary and final restoration phases. It was concluded that esthetics in implant-supported prostheses results from a multidisciplinary approach from planning until insertion of the final restoration. PMID- 22066513 TI - In situ identification of keratin-hydrolyzing organisms in swine manure inoculated anaerobic digesters. AB - Feathers, a poultry byproduct, are composed of > 90% keratin which is resistant to degradation during anaerobic digestion. In this study, four 42-L anaerobic digesters inoculated with adapted swine manure were used to investigate feather digestion. Ground feathers were added into two anaerobic digesters for biogas production, whereas another two without feathers were used as negative control. Feather degradation and enhanced methane production were recorded. Keratin hydrolyzing organisms (KHOs) were visualized in the feather bag fluids after boron-dipyrromethene (BODIPY) fluorescence casein staining. Their abundances correlated (R(2) = 0.96) to feather digestion rates. A 16S rRNA clone library was constructed for the bacterial populations attached to the feather particles. Ninety-three clones (> 1300 bp) were retrieved and 57 (61%) belonged to class Clostridia in the phylum Firmicutes, while 34 (37%) belonged to class Bacteroidia in the phylum Bacteroidetes. Four oligonucleotide FISH probes were designed for the major Clostridia clusters and used with other FISH probes to identify the KHOs. Probe FIMs1029 hybridized with most (> 80%) of the KHOs. Its targeted sequence perfectly matches that possessed by 10 Clostridia 16S rRNA gene clones belonging to a previously uncharacterized new genus closely related to Alkaliphilus in the subfamily Clostridiaceae 2 of family Clostridiaceae. PMID- 22066514 TI - Errata. PMID- 22066515 TI - ZINC TOLERANCE INDUCED BY IRON 1 reveals the importance of glutathione in the cross-homeostasis between zinc and iron in Arabidopsis thaliana. AB - Zinc is an essential micronutrient for plants, but it is toxic in excess concentrations. In Arabidopsis, additional iron (Fe) can increase Zn tolerance. We isolated a mutant, zinc tolerance induced by iron 1, designated zir1, with a defect in Fe-mediated Zn tolerance. Using map-based cloning and genetic complementation, we identified that zir1 has a mutation of glutamate to lysine at position 385 on gamma-glutamylcysteine synthetase (GSH1), the enzyme involved in glutathione biosynthesis. The zir1 mutant contains only 15% of the wild-type glutathione level. Blocking glutathione biosynthesis in wild-type plants by a specific inhibitor of GSH1, buthionine sulfoximine, resulted in loss of Fe mediated Zn tolerance, which provides further evidence that glutathione plays an essential role in Fe-mediated Zn tolerance. Two glutathione-deficient mutant alleles of GSH1, pad2-1 and cad2-1, which contain 22% and 39%, respectively, of the wild-type glutathione level, revealed that a minimal glutathione level between 22 and 39% of the wild-type level is required for Fe-mediated Zn tolerance. Under excess Zn and Fe, the recovery of shoot Fe contents in pad2-1 and cad2-1 was lower than that of the wild type. However, the phytochelatin deficient mutant cad1-3 showed normal Fe-mediated Zn tolerance. These results indicate a specific role of glutathione in Fe-mediated Zn tolerance. The induced accumulation of glutathione in response to excess Zn and Fe suggests that glutathione plays a specific role in Fe-mediated Zn tolerance in Arabidopsis. We conclude that glutathione is required for the cross-homeostasis between Zn and Fe in Arabidopsis. PMID- 22066516 TI - Relation between NT-proBNP levels, iron overload, and early stage of myocardial dysfunction in beta-thalassemia major patients. AB - BACKGROUND: Heart failure (HF) secondary to myocardial iron loading remains the leading cause of death in beta-thalassemia major (beta-TM) patients. The early diagnosis and treatment of HF in these patients is related to survival. We aimed to evaluate myocardial performance using conventional and tissue Doppler echocardiography and its relation to plasma NT-proBNP levels and iron overload indices in beta-TM patients with preserved systolic function. METHODS: The study population included 49 beta-TM patients (24.0 +/- 4.2 years) and 48 age-matched healthy controls. Doppler-echocardiographic study was performed and blood samples for NT-proBNP measurements were drawn on the third day following blood transfusion. Patients were divided as group-1, without diastolic dysfunction: E/E' ratio < 9 and group-2, with suspected diastolic dysfunction: E/E' ratio >= 9. RESULTS: NT-proBNP levels and E/E' ratio were increased in patients compared with controls (P < 0.001 and P < 0.001) but did not correlate with each other. A strong positive correlation was detected between NT-proBNP levels and mean ferritin levels in beta-TM patients (r(s) = 0.939; P < 0.001). Median NT-proBNP levels were significantly higher in group-1 in comparison to controls [51.2 (41.51-113.5) vs 30.1 (17.97-68.16) ng/mL, P < 0.01]. NT-proBNP levels were also increased in group-2 in comparison to group-1 but this increase was not statistically significant. CONCLUSION: NT-proBNP secretion begins in the early phase of the disease before the increase in diastolic pressure becomes overt. While there was a strong correlation between the plasma NT-proBNP levels and iron overload, there was no correlation between NT-proBNP levels and diastolic dysfunction parameters in patients in the third decade of life. PMID- 22066517 TI - Coxiella burnetii vaginal shedding and antibody responses in dairy goat herds in a context of clinical Q fever outbreaks. AB - This study, carried out in three goat herds, was aimed at describing individual responses to Q fever infection in an abortive context, focusing on both antibody and shedding levels. Seroprevalence of Coxiella burnetii (Cb) infection and vaginal shedding of 1083 goats were investigated using ELISA and realtime qPCR assays, respectively. At the end of the outbreaks, a seroprevalence of 45.0% was found, and vaginal shedding appeared massive with levels above 10(4) Cb per swab in 42.3% of the whole population and above 10(6) Cb per swab for 90.9% of aborted goats. Susceptible animals (i.e. seronegative nonshedders) were unfrequent (31.2%), most of them being kids (94.7%). Seronegative females were predominant among nonshedders and conversely seropositive ones, predominant among high shedders (above 10(6) Cb per swab). Nevertheless, at least 43.3% of seronegative goats shed bacteria confirming the need of interpreting serology on a herd scale. The subsequent farrowing period was characterized by a significant reduction in the number of clinical cases. Females that had already aborted were more often involved than others. Shedding quantities remained high, particularly for primiparous does, mainly when facing infection for the first time. Thus, Q fever control must be based on both preventive measures directed to the preherd and environmental precautions. PMID- 22066518 TI - A new design for an old concept of wheelchair pushrim. AB - PURPOSE: Report on the development of an ergonomic manual wheelchair pushrim and evaluate the user's perception of the quality of the device. METHOD: Based on anthropometric features and ergonomic concepts, a new wheelchair pushrim was designed, and a prototype was manufactured in polyurethane, using the rapid prototyping technique and serial production of parts by molding. The prototype was tested by a sample of wheelchair users, who rated the perceived quality of the device after testing both the new and conventional pushrims in a wheelchair propulsion experimental protocol. RESULTS: The new ergonomic pushrim was found to be, in general, better than the conventional round tube pushrim. Specifically, experienced wheelchair users found the new wheelchair pushrim better in terms of easy and comfortable propulsion, braking and maneuvering of the wheelchair, and appearance. CONCLUSIONS: The new wheelchair pushrim provides a proper fit for the hands due to its ergonomic design and its polyurethane composition, making wheelchair propulsion easier and more comfortable than the conventional wheelchair pushrim. Assistive technology devices should be design based on ergonomic concepts that involve less effort and offer greater comfort for the user. [Box: see text]. PMID- 22066519 TI - Nephrotoxicity of recreational party drugs. AB - N-benzylpiperazine (BZP) is the active ingredient in recreational 'party' pills with a stimulant, euphoric mechanism of action akin to that of 3,4 methylenedioxymethamphetamine (MDMA or ecstasy). Many people (ab)use BZP-based party pills usually without any significant toxic effects. However, nephrotoxicity secondary to hyperthermia and rhabdomyolysis has been reported. Another serious renal-related side-effect is hyponatraemia with acute cerebral oedema. There is also evidence that these agents may have a specific toxic effect producing acute kidney injury. Thus, acute kidney injury either direct or secondary to the effects of BZP or MDMA need to be considered when any individual presents with symptoms of a recreational party drug overdose. PMID- 22066520 TI - Restriction of the growth of a nonpathogenic spotted fever group rickettsia. AB - The growth kinetics of pathogenic and nonpathogenic rickettsiae were compared to elucidate the mechanism responsible for the pathogenicity of rickettsiae. Vero and HeLa cells derived from mammals were inoculated with a nonpathogenic species of spotted fever group rickettsia, Rickettsia montanensis, before being infected with the pathogenic species Rickettsia japonica. The mammalian cells became persistently infected with R. montanensis and produced low levels of rickettsiae. On the other hand, superinfection of the R. montanensis-infected cells with R. japonica resulted in increased yields of R. montanensis accompanied by R. japonica growth. Both rickettsiae also grew well in the R. japonica-infected cells subjected to superinfection with R. montanensis. Western blotting with an antibody to the autophagy-related protein LC3B found that autophagy was induced in the cells infected with R. montanensis alone. On the contrary, autophagy was restricted in the cells that were co-infected with R. japonica. Electron microscopy of the cells infected with R. montanensis alone demonstrated rickettsia particles being digested in intracytoplasmic vacuoles. Conversely, many freely growing rickettsiae were detected in the co-infected cells. PMID- 22066521 TI - Feasibility of an obesity intervention for paediatric primary care targeting parenting and children: Helping HAND. AB - BACKGROUND: The primary care setting offers the opportunity to reach children and parents to encourage healthy lifestyle behaviours, and improve weight status among children. OBJECTIVE: Test the feasibility of Helping HAND (Healthy Activity and Nutrition Directions), an obesity intervention for 5- to 8-year-old children in primary care clinics. METHODS: A randomized controlled pilot study of Helping HAND, a 6-month intervention, targeted children with body mass index 85-99%tile and their parents. Intervention group attended monthly sessions and self-selected child behaviours and parenting practices to change. Control group received regular paediatric care and was wait-listed for Helping HAND. Session completion, participant satisfaction, child anthropometrics, dietary intake, physical activity, TV viewing and behaviour-specific parenting practices were measured pre and post intervention. RESULTS: Forty parent-child dyads enrolled: 82.5% were Hispanic, 80% had a girl and 65% reported income <= $30, 000/year. There was 20% attrition from Helping HAND (attended <4/6 sessions). Families self selected 4.35 (SD 1.75) behaviours to target during the 6-month programme and each of the seven behaviours was selected by 45-80% of the families. There were no between group differences in the child's body mass index z-score, dietary intake or physical activity post intervention. Intervention group viewed 14.9 (SE 2.3) h/week of TV post intervention versus control group 23.3 (SE 2.4) h/week (P < 0.05). CONCLUSION: Helping HAND is feasible, due to low attrition, good programme attendance, and clinically relevant improvements in some child and parenting behaviours. PMID- 22066522 TI - Direct measurements of the rate constants of the reactions NCN + NO and NCN + NO2 behind shock waves. AB - The high-temperature rate constants of the reactions NCN + NO and NCN + NO(2) have been directly measured behind shock waves under pseudo-first-order conditions. NCN has been generated by the pyrolysis of cyanogen azide (NCN(3)) and quantitatively detected by sensitive difference amplification laser absorption spectroscopy at a wavelength of 329.1302 nm. The NCN(3) decomposition initially yields electronically excited (1)NCN radicals, which are subsequently transformed to the triplet ground state by collision-induced intersystem crossing (CIISC). CIISC efficiencies were found to increase in the order of Ar < NO(2) < NO as the collision gases. The rate constants of the NCN + NO/NO(2) reactions can be expressed as k(NCN+NO)/(cm(3) mol(-1)s(-1)) = 1.9 * 10(12) exp[-26.3 (kJ/mol)/RT] (+/-7%,DeltaE(a) = +/- 1.6 kJ/mol, 764 K < T < 1944 K) and k(NCN+NO(2))/(cm(3) mol(-1)s(-1)) = 4.7 * 10(12) exp[-38.0(kJ/mol)/RT] (+/ 19%,DeltaE(a) = +/- 3.8 kJ/mol, 704 K < T < 1659 K). In striking contrast to reported low-temperature measurements, which are dominated by recombination processes, both reaction rates show a positive temperature dependence and are independent of the total density (1.7 * 10(-6) mol/cm(3) < rho < 7.6 * 10(-6) mol/cm(3)). For both reactions, the minima of the total rate constants occur at temperatures below 700 K, showing that, at combustion-relevant temperatures, the overall reactions are dominated by direct or indirect abstraction pathways according to NCN + NO -> CN + N(2)O and NCN + NO(2) -> NCNO + NO. PMID- 22066523 TI - Acral peeling skin syndrome: a clinically and genetically heterogeneous disorder. AB - Acral peeling skin syndrome (APSS) is a rare, autosomal, recessive genodermatosis characterized by painless spontaneous exfoliation of the skin of the hands and feet at a subcorneal or intracorneal level. It usually presents at birth or appears later in childhood or early adulthood. Some cases result from mutations in the TGM5 gene that encodes transglutaminase 5, which has an important role in cross-linking cornified cell envelope proteins. We report a new APSS pedigree from Jordan that contains at least 10 affected family members, although sequencing of the TGM5 gene failed to disclose any pathogenic mutation(s). On the basis of probable consanguinity, we performed homozygosity mapping and identified areas of homozygosity on chromosomes 1, 6, 10, 13, and 16, although none of the intervals contained genes of clear relevance to cornification. APSS is a clinically and genetically heterogeneous disorder, and this Jordanian pedigree underscores the likelihood of still further heterogeneity. PMID- 22066524 TI - Examining mechanisms of groundwater Hg(II) treatment by reactive materials: an EXAFS study. AB - Laboratory batch experiments were conducted to examine mechanisms of Hg(II) removal by reactive materials proposed for groundwater treatment. These materials included granular iron filings (GIF), 1:1 (w/w) mixtures of metallurgical granular Fe powder + elemental S (MGI+S) and elemental Cu + elemental S (Cu+S), granular activated carbon (GAC), attapulgite clay (ATP), ATP treated with 2-amino 5-thiol-1,3,4-thiadiazole (ATP-a), and ATP treated with 2,5-dimercapto-1,3,4 thiadiazole (ATP-d). Following treatment of simulated groundwater containing 4 mg L(-1) Hg for 8 or 16 days, the solution pH values ranged from 6.8 to 8.8 and Eh values ranged from +400 to -400 mV. Large decreases in aqueous Hg concentrations were observed for ATP-d (>99%), GIF (95%), MGI+S (94%), and Cu+S (90%). Treatment of Hg was less effective using ATP (29%), ATP-a (69%), and GAC (78%). Extended X ray absorption fine structure (EXAFS) spectra of Hg on GIF, MGI+S, and GAC indicated the presence of an Hg-O bond at 2.04-2.07 A, suggesting that Hg was bound to GIF corrosion products or to oxygen complexes associated with water sorbed to activated carbon. In contrast, bond lengths ranging from 2.35 to 2.48 A were observed for Hg in Cu+S, ATP-a, and ATP-d treatments, suggesting the formation of Hg-S bonds. PMID- 22066525 TI - Novel 3,4-isoxazolediamides as potent inhibitors of chaperone heat shock protein 90. AB - A structural investigation on the isoxazole scaffold led to the discovery of 3,4 isoxazolediamide compounds endowed with potent Hsp90 inhibitory properties. We have found that compounds possessing a nitrogen atom directly attached to the C-4 heterocycle ring possess in vitro Hsp90 inhibitory properties at least comparable to those of the structurally related 4,5-diarylisoxazole derivatives. A group of compounds from this series of diamides combine potent binding affinity and cell growth inhibitory activity in both series of alkyl- and aryl- or heteroarylamides, with IC50 in the low nanomolar range. The 3,4-isoxazolediamides were also very effective in causing dramatic depletion of the examined client proteins and, as expected for the Hsp90 inhibitors, always induced a very strong increase in the expression levels of the chaperone Hsp70. In vivo studies against human epidermoid carcinoma A431 showed an antitumor effect of morpholine derivative 73 comparable to that induced by the reference compound 10. PMID- 22066526 TI - Is carbohydrate counting enough? Towards perfection or unwanted complexity? PMID- 22066527 TI - The cost-effectiveness of saxagliptin versus NPH insulin when used in combination with other oral antidiabetes agents in the treatment of type 2 diabetes mellitus in Poland. AB - BACKGROUND: This study compared the health and economic benefits of saxagliptin versus insulin as second-line therapy with either metformin (MET) or sulfonylurea (SU) after failure of the respective monotherapies for patients with type 2 diabetes in Poland. METHODS: The cost-effectiveness was assessed using a previously published diabetes model. Disease progression, utilities, and effects of changes in glycosylated hemoglobin (HbA1c), weight, and hypoglycemic events were taken from published studies, and Polish sources were used where possible. RESULTS: MET + saxagliptin reduced severe hypoglycemic complications and weight versus MET + insulin, with an incremental benefit of 0.13 quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) of 27,454 Polish zloty (PLN) ($9,966 U.S.) per QALY gained. SU + saxagliptin showed an incremental benefit of 0.14 QALYs and ICER of 24,663 PLN ($8,953 U.S.) per QALY gained versus SU + insulin, with reduced incidence of symptomatic and severe hypoglycemias. Results were most sensitive to disutilities associated with weight gain, hypoglycemia, injection fear, HbA1c changes, threshold for switching treatment, and patients' age. Results were robust to various model assumptions and inputs. Using a willingness-to-pay threshold of 100,000 PLN ($36,300 U.S.) per QALY gained, the probability that saxagliptin is cost-effective in these analyses was 74% (MET) and 76% (SU). CONCLUSIONS: Saxagliptin in combination with MET or SU is likely to represent a cost-effective treatment option in Polish patients with type 2 diabetes failing first-line treatment. PMID- 22066528 TI - Evidence of a discrete axial structure in unimodal collagen fibrils. AB - The collagen fibrils of cornea, blood vessel walls, skin, gut, interstitial tissues, the sheath of tendons and nerves, and other connective tissues are known to be made of helically wound subfibrils winding at a constant angle to the fibril axis. A critical aspect of this model is that it requires the axial microfibrils to warp in an implausible way. This architecture lends itself quite naturally to an epitaxial layout where collagen microfibrils envelop a central core of a different nature. Here we demonstrate an axial domain in collagen fibrils from rabbit nerve sheath and tendon sheath by means of transmission electron microscopy after a histochemical reaction designed to evidence all polysaccharides and by tapping-mode atomic force microscopy. This axial domain was consistently found in fibrils with helical microfibrils but was not observed in tendon, whose microfibrils run longitudinal and parallel. PMID- 22066529 TI - Activation of RIG-I-like receptor signal transduction. AB - Mammalian cells have the ability to recognize virus infection and mount a powerful antiviral response. Pattern recognition receptor proteins detect molecular signatures of virus infection and activate antiviral signaling cascades. The RIG-I-like receptors are cytoplasmic DExD/H box proteins that can specifically recognize virus-derived RNA species as a molecular feature discriminating the pathogen from the host. The RIG-I-like receptor family is composed of three homologous proteins, RIG-I, MDA5, and LGP2. All of these proteins can bind double-stranded RNA species with varying affinities via their conserved DExD/H box RNA helicase domains and C-terminal regulatory domains. The recognition of foreign RNA by the RLRs activates enzymatic functions and initiates signal transduction pathways resulting in the production of antiviral cytokines and the establishment of a broadly effective cellular antiviral state that protects neighboring cells from infection and triggers innate and adaptive immune systems. The propagation of this signal via the interferon antiviral system has been studied extensively, while the precise roles for enzymatic activities of the RNA helicase domain in antiviral responses are only beginning to be elucidated. Here, current models for RLR ligand recognition and signaling are reviewed. PMID- 22066530 TI - Randomised clinical trial: a comparative study of 10-day sequential therapy with 7-day standard triple therapy for Helicobacter pylori infection in naive patients. AB - BACKGROUND: The eradication rates following standard triple therapy for Helicobacter pylori infection are declining worldwide. Recent studies have shown that sequential therapy for H. pylori infection yields high cure rates. AIM: To compare the efficacy and tolerability of a sequential regimen as first-line treatment of H. pylori infection with a standard triple regimen. METHODS: A total of 348 naive H. pylori-infected patients from six hospitals in Korea were assigned randomly to standard triple or sequential therapy groups. Standard triple therapy consisted of 20 mg of rabeprazole, 1 g of amoxicillin and 500 mg of clarithromycin, twice daily for 7 days. Sequential therapy consisted of a 5 day dual therapy (20 mg of rabeprazole and 1 g of amoxicillin, twice daily) followed by a 5-day triple therapy (20 mg of rabeprazole, 500 mg of clarithromycin, and 500 mg of metronidazole, twice daily). RESULTS: The intention to-treat (ITT) and per-protocol (PP) eradication rates were 62.2% (95% CI 54.8 69.6%) and 76.0% (95% CI 68.5-83.5%) in the standard triple group, and 77.8% (95% CI 71.4-84.2%) and 87.9% (95% CI 82.3-93.5%) in the sequential group, respectively. The eradication rate was significantly higher in the sequential group compared with the standard triple group in both the ITT and PP populations (P = 0.002 and P = 0.013 respectively), whereas the incidence of adverse events was similar. CONCLUSIONS: Ten-day sequential therapy is more effective and equally tolerated for eradication of H. pylori infection compared with standard triple therapy. Sequential therapy may have a role as first-line treatment for H. pylori infection. PMID- 22066531 TI - Bacterial cytoplasm production of an EGFP-labeled single-chain Fv antibody specific for the HER2 human receptor. AB - The human epidermal growth factor receptor 2 (HER2) is the main diagnostic marker of breast and ovary cancers. Here, to obtain a rapid and sensitive immunodiagnostic tool a single-chain antibody (scFv800E6) specific for the HER2 was fused to the N-terminus of the enhanced green fluorescent protein (EGFP) by a flexible linker. The soluble production of the novel scFv800E6-EGFP protein in the cytoplasm of Escherichia coli was investigated at different induction temperatures (25, 30 and 37 degrees C); the intrinsic fluorescent properties and the binding activity to HER2 positive tumour cells of the fusion protein were analysed. Western blotting and fluorescence analysis of SDS-PAGE revealed the presence of two scFv800E6-EGFP forms, with different mobility and optical properties, their ratio depending on the induction temperature. The fluorescent form maintained the optical fluorescence properties of EGFP and exhibited a binding activity to the HER2-expressing cells comparable to that of the non-fused scFv800E6. In addition, to provide an insight into the effect of the induction temperature on the molecular structure, the folding of the fusion protein was assessed at atomic level by performing molecular dynamics simulations of the homology-derived model of scFv800E6-EGFP at 300 K and 310 K. The comparison of the data collected at these two temperatures revealed that the higher temperature affects specific structural elements. To improve the production of the soluble and functional scFv800E6-EGFP protein, "in silico" results could be utilised for ad hoc design of the molecular structure. PMID- 22066532 TI - Role of salt bridge dynamics in inter domain recognition of human IMPDH isoforms: an insight to inhibitor topology for isoform-II. AB - Inosine monophosphate dehydrogenase (IMPDH) enzyme involves in the biosynthesis pathway of guanosine nucleotide. Type II isoform of the enzyme is selectively upregulated in neoplastic fast replicating lymphocytes and CML cancer cells. The hIMPDH-II is an excellent target for antileukemic agent. The detailed investigation during MD-Simulation (15 ns) of three different unliganded structures (1B3O, 1JCN and 1JR1) have clearly explored the salt bridge mediated stabilization of inter or intra domain (catalytic domains I(N), I(C) with res. Id. 28-111 and 233-504, whereas two CBS domains C1, C2 are 112-171 and 172-232) in IMPDH enzyme which are mostly inaccessible in their X-rays structures. The salt bridge interaction in I(N)---C1 inter-domain of hIMPDH-I, I(N)---C2 of IMPDH II and C1---I(C) of nhIMPDH-II are discriminative features among the isoforms. The I(N)---C2 recognition in hIMPDH-II (1B3O) is missing in type-I isoform (1JCN). The salt bridge interaction D232---K238 at the surface of protein and the involvement of three conserved water molecules or the hydrophilic centers (WA232(OD1), WB 232(OD2) and W238(NZ)) to those acidic and basic residues seem to be unique in hIMPDH-II. The hydrophilic susceptibility, geometrical and electronic consequences of this salt bridge interaction could be useful to design the topology of specific inhibitor for hIMPDH-II which may not be effective for hIMPDH-I. Possibly, the aliphatic ligand containing carboxyl, amide or hydrophilic groups with flexible structure may be implicated for hIMPDH-II inhibitor design using the conserved water mimic drug design protocol. PMID- 22066533 TI - The effect of thiobarbituric acid on tyrosinase: inhibition kinetics and computational simulation. AB - Tyrosinase plays various roles in organisms and much research has focused on the regulation of tyrosinase activity. We studied the inhibitory effect of thiobarbituric acid (TBA) on tyrosinase. Our kinetic study showed that TBA inhibited tyrosinase in a reversible noncompetitive manner (K(i) 5 14.0 +/- 8.5 mM and IC50 5 8.0 +/- 1.0 mM). Intrinsic and ANS-binding fluorescences studies were also performed to gain more information regarding the binding mechanism. The results showed that no tertiary structural changes were obviously observed. For further insight, we predicted the 3D structure of tyrosinase and simulated the docking between tyrosinase and TBA. The docking simulation was successful with significant scores (binding energy for AutoDock4: -5.52 kcal/mol) and suggested that TBA was located in the active site. The 11 ns molecular dynamics simulation convinced that the four HIS residues (residue numbers: 57, 90, 250, and 282) were commonly responsible for the interaction with TBA. Our results provide a new inhibition strategy that works using an antioxidant rather than targeting the copper ions within the tyrosinase active site. PMID- 22066534 TI - Lose weight with traditional chinese medicine? Potential suppression of fat mass and obesity-associated protein. AB - Overweight and obesity are common health problems in modern society, particularly in developed countries. Excessive body mass has been linked to numerous diseases, such as cardiovascular diseases, diabetes, and cancer. Fat mass and obesity associated protein (FTO) activity have direct impact on food intake and results in obesity. Inhibition of FTO activity may cause weight loss and reduce obese linked health risks. We investigated the potential weight loss effects of traditional Chinese medicine (TCM), particularly by inhibiting FTO functions. Molecular docking was performed to screen TCM compounds from TCM Database@Taiwan (http://tcm.cmu.edu.tw). Three candidates were identified that contained either a tetrahydropyridine group or potent electronegative phenol group in the structure scaffold. Molecular dynamics simulation analysis of the docking poses of each complex indicated stabilizing trends in the protein-ligand complex movements. In addition, the number of hydrogen bonds increased throughout the 20 ns simulation. These results suggest that these TCM candidates could be potential FTO inhibitors through competitive inhibition. PMID- 22066535 TI - High-resolution crystal structure of spectrin SH3 domain fused with a proline rich peptide. AB - A new chimeric protein, named WT-CIIA, was designed by connecting the proline rich decapeptide PPPVPPYSAG to the C-terminus of the alpha-spectrin SH3 domain through a natural twelve-residue linker to obtain a single-chain model that would imitate intramolecular SH3-ligand interaction. The crystal structure of this fusion protein was determined at 1.7 A resolution. The asymmetric unit of the crystal contained two SH3 globules contacting with one PPPVPPY fragment located between them. The domains are related by the two-fold non-crystallographic axis and the ligand lies in two opposite orientations with respect to the conservative binding sites of SH3 domains. PMID- 22066536 TI - Mechanical transduction mechanisms of RecA-like molecular motors. AB - A majority of ATP-dependent molecular motors are RecA-like proteins, performing diverse functions in biology. These RecA-like molecular motors consist of a highly conserved core containing the ATP-binding site. Here I examined how ATP binding within this core is coupled to the conformational changes of different RecA-like molecular motors. Conserved hydrogen bond networks and conformational changes revealed two major mechanical transduction mechanisms: (1) intra-domain conformational changes and (2) inter-domain conformational changes. The intra domain mechanism has a significant hydrogen bond rearrangement within the domain containing the P-loop, causing relative motion between two parts of the protein. The inter-domain mechanism exhibits little conformational change in the P-loop domain. Instead, the major conformational change is observed between the P-loop domain and an adjacent domain or subunit containing the arginine finger. These differences in the mechanical transduction mechanisms may link to the underlying energy surface governing a Brownian ratchet or a power stroke. PMID- 22066537 TI - Dynamics of endoglucanase catalytic domains: implications towards thermostability. AB - Thermostable endoglucanases play a crucial role in the production of biofuels to breakdown plant cellulose. Analyzing their structure-dynamics relationship can inform about the origins of their thermostability. Although tertiary structures of many endoglucanase proteins are available, the relationship between thermostability, structure, and dynamics is not explored fully. We have generated elastic network models for thermostable and mesostable endoglucanases with the (alphabeta)8 fold in substrate bound and unbound states. The comparative analyses shed light on the relation between protein dynamics, thermostability, and substrate binding. We observed specific differences in the dynamic behavior of catalytic residues in slow modes: while both the nucleophile and the acid/base donor residues show positively correlated motions in the thermophile, their dynamics is uncoupled in the mesophile. Our proof-of-concept comparison study suggests that global dynamics can be harnessed to further our understanding of thermostability. PMID- 22066538 TI - Why the OPLS-AA force field cannot produce the beta-hairpin structure of H1 peptide in solution when comparing with the GROMOS 43A1 force field? AB - The optimal combination of force field and water model is an essential problem that is able to increase molecular dynamics simulation quality for different types of proteins and peptides. In this work, an attempt has been made to explore the problem by studying H1 peptide using four different models based on different force fields, water models and electrostatic schemes. The driving force for H1 peptide conformation transition and the reason why the OPLS-AA force field cannot produce the beta-hairpin structure of H1 peptide in solution while the GROMOS 43A1 force field can do were investigated by temperature replica exchange molecular dynamics simulation (T-REMD). The simulation using the GROMOS 43A1 force field preferred to adopt a beta-hairpin structure, which was in good agreement with the several other simulations and the experimental evidences. However, the simulation using the OPLS-AA force field has a significant difference from the simulations with the GROMOS 43A1 force field simulation. The results show that the driving force in H1 peptide conformation transition is solvent exposure of its hydrophobic residues. However, the subtle balances between residue-residue interactions and residue-solvent interaction are disrupted by using the OPLS-AA force field, which induced the reduction in the number of residue-residue contact. Similar solvent exposure of the hydrophobic residues is observed for all the conformations sampled using the OPLS-AA force field. For H1 peptide which exhibits large solvent exposure of the hydrophobic residues, the GROMOS 43A1 force field with the SPC water model can provide more accurate results. PMID- 22066539 TI - Structure and energy of non-canonical basepairs: comparison of various computational chemistry methods with crystallographic ensembles. AB - Different types of non-canonical basepairs, in addition to the Watson-Crick ones, are observed quite frequently in RNA. Their importance in the three dimensional structure is not fully understood, but their various roles have been proposed by different groups. We have analyzed the energetics and geometry of 32 most frequently observed basepairs in the functional RNA crystal structures using different popular empirical, semi-empirical and ab initio quantum chemical methods and compared their optimized geometry with the crystal data. These basepairs are classified into three categories: polar, non-polar and sugar mediated, depending on the types of atoms involved in hydrogen bonding. In case of polar basepairs, most of the methods give rise to optimized structures close to their initial geometry. The interaction energies also follow similar trends, with the polar ones having more attractive interaction energies. Some of the C H...O/N hydrogen bond mediated non-polar basepairs are also found to be significantly stable in terms of their interaction energy values. Few polar basepairs, having amino or carboxyl groups not hydrogen bonded to anything, such as G:G H:W C, show large flexibility. Most of the non-polar basepairs, except A:G s:s T and A:G w:s C, are found to be stable; indicating C-H...O/N interaction also plays a prominent role in stabilizing the basepairs. The sugar mediated basepairs show variability in their structures, due to the involvement of flexible ribose sugar. These presumably indicate that the most of the polar basepairs along with few non-polar ones act as seed for RNA folding while few may act as some conformational switch in the RNA. PMID- 22066540 TI - Unique hole-trapping property of the human telomere sequence. AB - The hypothetical protection of genes from oxidative damage provided by the G-rich telomeric overhangs located at the end of chromosomes, which consist, in humans, of single strands of TTAGGG sequence repeats, is investigated here. First principle Moller-Plesset perturbation theory calculations reveal that the TTAGGG human telomere sequence is particularly prone to oxidation and can act as a profound hole trap as deep as a sequence of five consecutive guanines. In addition, we show that the sequence dependence is very important and that modifications in the human telomeric sequence can induce crucial changes in the electronic structure of the sequence, with concomitant increase of the ionization energy. These theoretical results provide, for the first time, quantitative data indicating a high and unique efficiency of the human telomeric sequence as a trap in long-range hole migration which will aid in the design of subsequent experiments. PMID- 22066541 TI - How flexible are DNA constituents? The quantum-mechanical study. AB - Relaxed force constants (RFCs) and vibrational root-mean-square deviations have been evaluated by the original calculation method for conformational parameters of the DNA structural units and their constituents: nucleic acid bases (uracile, thymine, cytosine, adenine and guanine) and their 'building blocks' (benzene, pyrimidine, imidazole and purine molecules), as well as the DNA backbone structural units: tetrahydrofuran, 1,2-dideoxyribose, methanol and orthophosphoric acid. It has been found that the RFCs for nomenclature torsions beta, gamma, epsilon; and sugar pseudorotation angle P in 1,2-dideoxyribose are sensible to the molecule conformation and their values are in the range of 1-25 kcal/(mole.rad2) obeying the inequality K(gamma)> K(epsilon) > K(rho) > K(beta). The RFCs values for endocyclic torsions of nucleic acid bases six-member rings lie within 15-45 kcal/(mole.rad2) in pyrimidines and within 20-60 kcal/(mole.rad2) in purines. It is shown that the quantum zero-point motion effectively neglects the amino group non-planarity in cytosine, adenine and partially in guanine. PMID- 22066542 TI - Nucleosome positioning patterns derived from human apoptotic nucleosomes. AB - This communication reports on the nucleosome positioning patterns (bendability matrices) for the human genome, derived from over 8_million nucleosome DNA sequences obtained from apoptotically digested lymphocytes. This digestion procedure is used here for the first time for the purpose of extraction and sequencing of the nucleosome DNA fragments. The dominant motifs suggested by the matrices of DNA bendability calculated for light and heavy isochores are significantly different. Both, however, are in full agreement with the linear description YRRRRRYYYYYR, and with earlier derivations by N-gram extensions. Thus, the choice of the nucleosome positioning patterns crucially depends on the G + C composition of the analyzed sequences. PMID- 22066543 TI - Effect of the alkaline cations on the stability of the model polynucleotide poly(dG-dC).poly(dG-dC). AB - When the model polynucleotide poly(dG-dC)?poly(dG-dC) [polyGC] is titrated with a strong acid (HCl) in unbuffered aqueous solutions containing the chlorides of the alkali metals in the concentration range 0.010 M-0.600 M, two transitions in the absorbance vs. pH plots are evidenced, characterized by the constants pK(a(1)) and pK(a(2)). The limiting values at infinite saline concentrations of these two constants, namely pK(infinity)(a(1)) and pK(infinity)(a(2)) obtained making use of the "one site saturation constant" equation or, in turn, of the double logarithmic plot: pK(a) vs. log([salt]-1), exhibit a clear dependence on the nature of the cations. The effects of the different alkali cations on the pK(infinity)(a) values follow the Hofmeister series. In fact, the pK(infinity)(a(1)) and the pK(infinity)(a(2)) values are smaller for Li+ and Na+ than for Rb+ and Cs+, with K+ at the border between the two, showing that the transitions require higher concentrations of protons to occur in the presence of high concentrations of the cosmotropic ions. PMID- 22066544 TI - Retraction: Molecular modeling and molecular dynamics simulation studies of Delta Notch complex. AB - Majumder R, Roy, S, Thakur AR, J Biomol Struct Dyn .2011 Oct;29(2):297-310. According to a letter that the Journal received as an attachment to an email dated September 27, 2011 from the senior author Prof. Ashoke Ranjan Thakur, they have indicated to have their paper retracted, because an original reviewer raised questions (when he saw the published copy) regarding the correctness assignment of a residue number in their calculation. The authors have already started the recalculation. They intend to submit the whole paper back again for consideration for publication in a future issue of the Journal. PMID- 22066545 TI - Predictive value of the baseline T-QRS ratio of the fetal electrocardiogram in intrapartum fetal monitoring: a prospective cohort study. AB - OBJECTIVE: To evaluate the added value of the baseline T/QRS ratio to other known risk factors in predicting adverse outcome and interventions for suspected fetal distress. DESIGN: Prospective cohort study. SETTING: Three academic and six non academic teaching hospitals in the Netherlands. POPULATION: Laboring women with a high-risk cephalic singleton pregnancy beyond 36 weeks of gestation. METHODS: We obtained STAN((r)) recordings (ST-analysis, Neoventa, Sweden) from two previous studies. Three patient groups were defined: cases with adverse outcome, cases with emergency delivery because of suspected fetal distress without adverse outcome, and a reference group of uncomplicated cases. Baseline T/QRS ratios among the adverse outcome and intervention for suspected fetal distress cases were compared to those of the uncomplicated cases. The ability of baseline T/QRS to predict adverse outcome and suspected fetal distress was determined using a multivariable logistic model. MAIN OUTCOME MEASURES: The added value of the baseline T/QRS to other known risk factors in the prediction of adverse outcome and interventions for suspected fetal distress. RESULTS: From 3462 recordings, 2459 were available for analysis. Median baseline T/QRS for uncomplicated cases, adverse outcome and interventions for suspected fetal distress were 0.12 (range 0.00-0.52), 0.12 (0.00-0.42) and 0.13 (0.00-0.39), respectively. There was no statistical difference between these groups. Multivariable analysis showed no added value of baseline T/QRS in the prediction of either adverse outcome or interventions for suspected fetal distress. CONCLUSION: Baseline T/QRS has no added value in the prediction of adverse neonatal outcome or interventions for suspected fetal distress. PMID- 22066546 TI - Bacterial community composition in low-flowing river water with different sources of pollutants. AB - Pollution of water resources is a major risk to human health and water quality throughout the world. The purpose of this study was to determine the influence of pollutant sources from agricultural activities, urban runoffs, and runoffs from wastewater treatment plants (WWTPs) on bacterial communities in a low-flowing river. Bacterial community structure was monitored using terminal restriction fragment length polymorphism (T-RFLP) and 16S rRNA gene clone library. The results were analyzed using nonmetric multidimensional scaling (NMDS) and UniFrac, coupled with principal coordinate analysis (PCoA) to compare diversity, abundance, community structure, and specific functional groups of bacteria in surface water affected by nonpoint sources. From all the sampling points, Bacteria were numerically dominated by three phyla - the Proteobacteria, Bacteroidetes, and Cyanobacteria - accounting for the majority of taxa detected. Overall results, using the b diversity measures UniFrac, coupled with PCoA, showed that bacterial contamination of the low-flowing river was not significantly different between agricultural activities and urban runoff. PMID- 22066547 TI - Copper-mediated reduction of CO2 with pinB-SiMe2Ph via CO2 insertion into a copper-silicon bond. AB - Reaction of [(IPr)Cu-OtBu] (1) with pinB-SiMe(2)Ph (2) leads to the Cu-silyl complex [(IPr)Cu-SiMe(2)Ph] (3). Insertion of CO(2) into the Cu-Si bond of 3 is followed by transformation of the resulting silanecarboxy complex [(IPr)Cu O(2)CSiMe(2)Ph] (4) to the silanolate complex [(IPr)Cu-OSiMe(2)Ph] (5) via extrusion of CO. As 5 reacts readily with 2 to regenerate 3, a catalytic CO(2) reduction to CO is feasible. The individual steps were studied by in situ(13)C NMR spectroscopy of a series of stoichiometric reactions. Complexes 3, 4, and 5 were isolated and fully characterized, including single-crystal X-ray diffraction studies. Interestingly, the catalytic reduction of CO(2) using silylborane 2 as a stoichiometric reducing agent leads not only to CO and pinB-O-SiMe(2)Ph but also to PhMe(2)Si-CO(2)-SiMe(2)Ph as an additional reduction product. PMID- 22066548 TI - Autophagy in stem cell maintenance and differentiation. AB - Autophagy is a lysosome-dependent degradation pathway that allows cells to recycle damaged or superfluous cytoplasmic content, such as proteins, organelles, and lipids. As a consequence of autophagy, the cells generate metabolic precursors for macromolecular biosynthesis or ATP generation. Deficiencies in this pathway were associated to several pathological conditions, such as neurodegenerative and cardiac diseases, cancer, and aging. The aim of this review is to summarize recent discoveries showing that autophagy also plays a critical role in stem cell maintenance and in a variety of cell differentiation processes. We also discuss a possible role for autophagy during cellular reprogramming and induced pluripotent stem (iPS) cell generation by taking advantage of ATP generation for chromatin remodeling enzyme activity and mitophagy. Finally, the significance of autophagy modulation is discussed in terms of augmenting efficiency of iPS cell generation and differentiation processes. PMID- 22066549 TI - In consideration of GMOs: a virtual special issue of the Plant Biotechnology Journal. PMID- 22066551 TI - 10-year survival of total ankle arthroplasties: a report on 780 cases from the Swedish Ankle Register. AB - BACKGROUND AND PURPOSE: There is an ongoing need to review large series of total ankle replacements (TARs) for monitoring of changes in practice and their outcome. 4 national registries, including the Swedish Ankle Register, have previously reported their 5-year results. We now present an extended series with a longer follow-up, and with a 10-year survival analysis. PATIENTS AND METHODS: Records of uncemented 3-component TARs were retrospectively reviewed, determining risk factors such as age, sex, and diagnosis. Prosthetic survival rates were calculated with exchange or removal of components as endpoint-excluding incidental exchange of the polyethylene meniscus. RESULTS: Of the 780 prostheses implanted since 1993, 168 (22%) had been revised by June 15, 2010. The overall survival rate fell from 0.81 (95% CI: 0.79-0.83) at 5 years to 0.69 (95% CI: 0.67 0.71) at 10 years. The survival rate was higher, although not statistically significantly so, during the latter part of the period investigated. Excluding the STAR prosthesis, the survival rate for all the remaining designs was 0.78 at 10 years. Women below the age of 60 with osteoarthritis were at a higher risk of revision, but age did not influence the outcome in men or women with rheumatoid arthritis. Revisions due to technical mistakes at the index surgery and instability were undertaken earlier than revisions for other reasons. INTERPRETATION: The results have slowly improved during the 18-year period investigated. However, we do not believe that the survival rates of ankle replacements in the near future will approach those of hip and knee replacements even though improved instrumentation and design of the prostheses, together with better patient selection, will presumably give better results. PMID- 22066552 TI - Survival and prognostic factors in chondrosarcoma: results in 115 patients with long-term follow-up. AB - BACKGROUND AND PURPOSE: There have been few long-term studies on the outcome of chondrosarcoma and the findings regarding prognostic factors are controversial. We examined a homogeneous group of patients with primary central chondrosarcoma of bone who were treated according to a uniform surgical protocol at our institution, in order to determine the factors that influence survival and identify potential improvements to our therapeutic algorithm. PATIENTS AND METHODS: We performed a retrospective analysis of 115 patients with primary central chondrosarcoma of bone who presented with localized disease and who had a minimum follow-up of 5 years after diagnosis. 68 tumors were localized in the extremities and 47 in the axial skeleton or pelvis. 59 patients had a high-grade (II and III) and 56 a low-grade (I) tumor. 94 patients underwent surgical resection with adequate (wide or radical) margins, while 21 patients had inadequate (marginal or intralesional) margins. RESULTS: Tumor grade and localization were found to be statistically significant independent predictors of disease-related deaths in multivariate analysis. The quality of surgical margins did not influence survival. The AJCC staging system was able to predict prognosis in patients with chondrosarcoma of the extremities, but not in those with tumors of the axial skeleton and pelvis. Long-term survival after secondary metastatic disease was only observed when metastases were resected with wide margins. Patients with metastases who received further treatment with conventional chemotherapy, radiotherapy, and/or further surgery had significantly better survival compared to those who received best supportive care. INTERPRETATION: The outcome in patients with primary central chondrosarcoma of bone who present with localized disease is mostly affected by tumor-related parameters. PMID- 22066553 TI - High rate of complications and radiographic loosening of the biaxial total wrist arthroplasty in rheumatoid arthritis: 32 wrists followed for 6 (5-8) years. AB - BACKGROUND AND PURPOSE: The third generation of total wrist arthroplasty (TWA) was designed to solve the early loosening problem, but there have been few long term follow-ups. We present the outcome of the biaxial total wrist prosthesis (no longer available) after 5-8 years of follow-up. PATIENTS AND METHODS: 40 biaxial wrist prostheses were implanted uncemented in 36 patients with rheumatoid arthritis. 32 wrists were followed clinically and radiographically. 7 prostheses had been revised at median 21 (8-71) months; 1 patient died from an unrelated cause. Mean follow-up of the remaining 32 wrists was 6 (5-8) years. Kaplan-Meier survival analysis was performed with revision defined as failure. RESULTS: Survival after 7 years was 81% (95% CI: 64-91). There were 31 complications. 22 wrists showed radiographic loosening. Range of motion improved, except for pronation. The mean DASH score improved and the median postoperative pain score (from 0 to 10) was 0 (0-6) at rest and 0 (0-7) during activity. INTERPRETATION: One quarter of the prostheses had been revised and radiographic loosening had occurred in two thirds of the cases. Radiographic and clinical follow-up is therefore necessary for patients with this implant. PMID- 22066554 TI - Low infection rates after 34,361 intramedullary nail operations in 55 low- and middle-income countries: validation of the Surgical Implant Generation Network (SIGN) online surgical database. AB - BACKGROUND: The Surgical Implant Generation Network (SIGN) supplies intramedullary (IM) nails for the treatment of long bone fractures free of charge to hospitals in low- and middle-income countries (LMICs). Most operations are reported to the SIGN Online Surgical Database (SOSD). Follow-up has been reported to be low, however. We wanted to examine the pattern of follow-up and to assess whether infection rates could be trusted. PATIENTS AND METHODS: The SOSD contained 36,454 IM nail surgeries in 55 LMICs. We excluded humerus and hip fractures, and fractures without a registered surgical approach. This left 34,361 IM nails for analysis. A generalized additive regression model (gam) was used to explore the association between follow-up rates and infection rates. RESULTS: The overall follow-up rate in the SOSD was 18.1% (95% CI: 17.7-18.5) and national follow-up rates ranged from 0% to 74.2%. The overall infection rate was 0.7% (CI: 0.6-0.8) for femoral fractures and 1.2% (CI: 1.0-1.4) for tibial fractures. If only nails with a registered follow-up visit were included (n = 6,224), infection rates were 3.5% (CI: 3.0-4.1) for femoral fractures and 7.3% (CI: 6.2-8.4) for tibial fractures. We found an increase in infection rates with increasing follow up rates up to a level of 5%. Follow-up above 5% did not result in increased infection rates. INTERPRETATION: Reported infection rates after IM nailing in the SOSD appear to be reliable and could be used for further research. The low infection rates suggest that IM nailing is a safe procedure also in low- and middle-income countries. PMID- 22066555 TI - High degree of kinesiophobia after lumbar disc herniation surgery: a cross sectional study of 84 patients . AB - BACKGROUND AND PURPOSE: Several studies have investigated outcomes after disc surgery. However, the occurrence of kinesiophobia has not been investigated previously in patients after disc herniation surgery. In this cross-sectional study, we investigated kinesiophobia in patients who had been treated surgically for lumbar disc herniation, and we related the results to established outcome measures. PATIENTS AND METHODS: 10-34 months after surgery, questionnaires were sent to 97 patients who had undergone standardized open discectomy. Outcome measures included Tampa scale for kinesiophobia (TSK); Oswestry disability index (ODI); European quality of life in 5 dimensions (EQ-5D); visual analog scale (VAS) for leg and back pain, work disability, and patient satisfaction; Zung self rating depression scale (ZDS); pain catastrophizing scale (PCS); and a self efficacy scale (SES). RESULTS: 36 of 80 patients reported having kinesiophobia. There were statistically significant differences in ODI, EQ-5D, VAS leg and back pain, ZDS, PCS, and SES between patients with and without kinesiophobia. INTERPRETATION: Half of the patients suffered from kinesiophobia 10-34 months after surgery for disc herniation. These patients were more disabled, had more pain, more catastrophizing thoughts, more symptoms of depression, lower self efficacy, and poorer health-related quality of life than patients without kinesiophobia. PMID- 22066556 TI - Improved spinal fusion efficacy by long-term delivery of bone morphogenetic protein-2 in a rabbit model. AB - BACKGROUND AND PURPOSE: Various new delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2) have been introduced to improve its efficacy in osteogenesis. Of these, we have previously developed heparin-conjugated PLGA nanospheres (HCPN) as a long-term delivery system for BMP-2. In vitro studies have shown that the BMP-2 long-term delivery system enhances the level of bone formation. However, the long-term effects of BMP-2 on spinal fusion have not been assessed. Therefore, we now tested the hypothesis that the long-term delivery of BMP-2 using HCPN improves spinal fusion compared to short-term delivery in a rabbit fusion model. METHODS: 24 adult New Zealand White rabbits underwent posterolateral fusion (6 animals in 4 groups). The autograft group received an autologous iliac chip bone graft as a positive control. The BMP-2-PN group received rhBMP-2 (20 MUg per implant) and PLGA nanospheres (PN) suspended in fibrin gel, and served as a short-term release group. The HCPN group received HCPN suspended in fibrin gel without BMP-2 as a negative control. The BMP-2-HCPN group received rhBMP-2 (20 MUg per implant)-bound HCPN suspended in fibrin gel and served as a long-term release group. All animals were killed 12 weeks after surgery. Manual palpation, axial tensile tests, radiography, and histological evaluations were then performed. RESULTS: The spinal fusion rate and Young's modulus of the fusion mass were better in the BMP-2 long-term delivery group than in the short-term delivery group at an equivalent dose. However, the outcome of the long-term delivery was inferior to that of the autograft group. INTERPRETATION: The HCPN system showed potential as an effective carrier that might improve the osteogenic efficacy of BMP-2 for spinal fusion. PMID- 22066557 TI - Atypical fracture of the ulna associated with alendronate use. PMID- 22066558 TI - Maximum temperatures of 89 degrees C recorded during the mechanical preparation of 35 femoral heads for resurfacing. AB - BACKGROUND AND PURPOSE: We noticed that our instruments were often too hot to touch after preparing the femoral head for resurfacing, and questioned whether the heat generated could exceed temperatures known to cause osteonecrosis. PATIENTS AND METHODS: Using an infra-red thermal imaging camera, we measured real time femoral head temperatures during femoral head reaming in 35 patients undergoing resurfacing hip arthroplasty. 7 patients received an ASR, 8 received a Cormet, and 20 received a Birmingham resurfacing arthroplasty. RESULTS: The maximum temperature recorded was 89 degrees C. The temperature exceeded 47 degrees C in 28 patients and 70 degrees C in 11. The mean duration of most stages of head preparation was less than 1 min. The mean time exceeded 1 min only on peripheral head reaming of the ASR system. At temperatures lower than 47 degrees C, only 2 femoral heads were exposed long enough to cause osteonecrosis. The highest mean maximum temperatures recorded were 54 degrees C when the proximal femoral head was resected with an oscillating saw and 47 degrees C during peripheral reaming with the crown drill. The modified new Birmingham resurfacing proximal femoral head reamer substantially reduced the maximum temperatures generated. Lavage reduced temperatures to a mean of 18 degrees C. INTERPRETATION: 11 patients were subjected to temperatures sufficient to cause osteonecrosis secondary to thermal insult, regardless of the duration of reaming. In 2 cases only, the length of reaming was long enough to induce damage at lower temperatures. Lavage and sharp instruments should reduce the risk of thermal insult during hip resurfacing. PMID- 22066559 TI - Similar TKA designs with differences in clinical outcome: a randomized, controlled trial of 77 knees with a mean follow-up of 6 years. AB - BACKGROUND AND PURPOSE: To try to improve the outcome of our TKAs, we started to use the CKS prosthesis. However, in a retrospective analysis this design tended to give worse results. We therefore conducted a randomized, controlled trial comparing this CKS prosthesis and our standard PFC prosthesis. Because many randomized studies between different TKA concepts generally fail to show superiority of a particular design, we hypothesized that these seemingly similar designs would not lead to any difference in clinical outcome. PATIENTS AND METHODS: 82 patients (90 knees) were randomly allocated to one or other prosthesis, and 39 CKS prostheses and 38 PFC prostheses could be followed for mean 5.6 years. No patients were lost to follow-up. At each follow-up, patients were evaluated clinically and radiographically, and the KSS, WOMAC, VAS patient satisfaction scores and VAS for pain were recorded. RESULTS: With total Knee Society score (KSS) as primary endpoint, there was a difference in favor of the PFC group at final follow-up (p = 0.04). Whereas there was one revision in the PFC group, there were 6 revisions in the CKS group (p = 0.1). The survival analysis with any reoperation as endpoint showed better survival in the PFC group (97% (95% CI: 92-100) for the PFC group vs. 79% (95% CI: 66-92) for the CKS group) (p = 0.02). INTERPRETATION: Our hypothesis that there would be no difference in clinical outcome was rejected in this study. The PFC system showed excellent results that were comparable to those in previous reports. The CKS design had differences that had considerable negative consequences clinically. The relatively poor results have discouraged us from using this design. PMID- 22066560 TI - Why still in hospital after fast-track hip and knee arthroplasty? AB - BACKGROUND AND PURPOSE: Length of stay (LOS) following total hip and knee arthroplasty (THA and TKA) has been reduced to about 3 days in fast-track setups with functional discharge criteria. Earlier studies have identified patient characteristics predicting LOS, but little is known about specific reasons for being hospitalized following fast-track THA and TKA. PATIENTS AND METHODS: To determine clinical and logistical factors that keep patients in hospital for the first postoperative 24-72 hours, we performed a cohort study of consecutive, unselected patients undergoing unilateral primary THA (n = 98) or TKA (n = 109). Median length of stay was 2 days. Patients were operated with spinal anesthesia and received multimodal analgesia with paracetamol, a COX-2 inhibitor, and gabapentin-with opioid only on request. Fulfillment of functional discharge criteria was assessed twice daily and specified reasons for not allowing discharge were registered. RESULTS: Pain, dizziness, and general weakness were the main clinical reasons for being hospitalized at 24 and 48 hours postoperatively while nausea, vomiting, confusion, and sedation delayed discharge to a minimal extent. Waiting for blood transfusion (when needed), for start of physiotherapy, and for postoperative radiographic examination delayed discharge in one fifth of the patients. INTERPRETATION: Future efforts to enhance recovery and reduce length of stay after THA and TKA should focus on analgesia, prevention of orthostatism, and rapid recovery of muscle function. PMID- 22066561 TI - Risk of periprosthetic femur fracture after anterior cortical bone windowing: a mechanical analysis of short versus long cemented stems in pigs. AB - BACKGROUND AND PURPOSE: Removal of distal cement at femoral implant revision is technically challenging and is associated with complications such as cortical perforations. A technique that can reduce the risks and operating time is to make a small cortical window in the distal femur for enhanced access. We wanted to determine whether the use of long, bridging, cemented femoral stems is necessary to reduce the risk of postoperative periprosthetic fractures after using an anterior cortical bone window. METHODS: 66 fresh pig femurs underwent mechanical testing. Steel rods were implanted at 3 locations: (1) at the distal window edge, (2) 15 mm proximally to the cortical window edge, and (3) 15 mm distally. 54 femurs were tested using a 3-point bending setup and 12 femurs were tested using a torsional load setup. RESULTS: Load to fracture ratio and bending stiffness ratio were similar in the 3 groups, for either the 3-point bending test or the torsional load test. INTERPRETATION: Our findings suggest that bypass of cortical windows with a revision femoral component may not reduce the risk of periprosthetic fracture. PMID- 22066562 TI - Infection after primary hip arthroplasty: a comparison of 3 Norwegian health registers. AB - BACKGROUND AND PURPOSE: The aim of the present study was to assess incidence of and risk factors for infection after hip arthroplasty in data from 3 national health registries. We investigated differences in risk patterns between surgical site infection (SSI) and revision due to infection after primary total hip arthroplasty (THA) and hemiarthroplasty (HA). MATERIALS AND METHODS: This observational study was based on prospective data from 2005-2009 on primary THAs and HAs from the Norwegian Arthroplasty Register (NAR), the Norwegian Hip Fracture Register (NHFR), and the Norwegian Surveillance System for Healthcare Associated Infections (NOIS). The Norwegian Patient Register (NPR) was used for evaluation of case reporting. Cox regression analyses were performed with revision due to infection as endpoint for data from the NAR and the NHFR, and with SSI as the endpoint for data from the NOIS. RESULTS: The 1-year incidence of SSI in the NOIS was 3.0% after THA (167/5,540) and 7.3% after HA (103/1,416). The 1-year incidence of revision due to infection was 0.7% for THAs in the NAR (182/24,512) and 1.5% for HAs in the NHFR (128/8,262). Risk factors for SSI after THA were advanced age, ASA class higher than 2, and short duration of surgery. For THA, the risk factors for revision due to infection were male sex, advanced age, ASA class higher than 1, emergency surgery, uncemented fixation, and a National Nosocomial Infection Surveillance (NNIS) risk index of 2 or more. For HAs inserted after fracture, age less than 60 and short duration of surgery were risk factors of revision due to infection. INTERPRETATION: The incidences of SSI and revision due to infection after primary hip replacements in Norway are similar to those in other countries. There may be differences in risk pattern between SSI and revision due to infection after arthroplasty. The risk patterns for revision due to infection appear to be different for HA and THA. PMID- 22066563 TI - No improvement in long-term wear and revision rates with the second-generation Biomet cup (RingLoc) in young patients: 141 hips followed for median 12 years. AB - BACKGROUND: A number of excellent results with the cementless titanium femoral component of the Mallory Head Total Hip Replacement have been published. Unfortunately, these excellent results have been counteracted by the poor performance of the cementless titanium acetabular components. In 1994, the HexLoc acetabular component was replaced with a second-generation design, the RingLoc. We hypothesized that the new generation would have improved the results. METHODS: We retrospectively studied 111 consecutive patients (150 hips) younger than 55 years. Median follow-up time was 14 (6-18) years for the HexLoc and 10 (1-14) years for the RingLoc. 7 patients were lost to follow-up and 7 patients died. The 10-year survival rate, radiographic liner wear, and radiographic signs of prosthesis failure were compared between the 2 acetabular components. RESULTS: The Kaplan-Meier survival estimate with revision for any reason as the endpoint showed a 10-year survival of 89% (95% CI: 81-97) for the HexLoc and 92% (CI: 85 98) for the RingLoc. The mean annual wear rate for the HexLoc was 0.16 (SD 0.16) mm and it was 0.15 (0.1) mm for the RingLoc (p = 0.3). The radiographic signs of failure were equally distributed between the 2 groups. INTERPRETATION: Compared to the HexLoc type, the RingLoc system did not improve the mean percentage survival at 10 years; nor did it reduce the liner wear. Despite correction of the known design flaws in the HexLoc design, the RingLoc system did not show a clinically relevant improvement compared to its predecessor. PMID- 22066564 TI - Adverse events in spine surgery in Sweden: a comparison of patient claims data and national quality register (Swespine) data . AB - BACKGROUND AND PURPOSE: Our knowledge of complications and adverse events in spinal surgery is limited, especially concerning incidence and consequences. We therefore investigated adverse events in spine surgery in Sweden by comparing patient claims data from the County Councils' Mutual Insurance Company register with data from the National Swedish Spine Register (Swespine). METHODS: We analyzed patient claims (n = 182) to the insurance company after spine surgery performed between 2003 and 2005. The medical records of the patients filing these claims were reviewed and compared with Swespine data for the same period. RESULTS: Two-thirds (119/182, 65%) of patients who claimed economic compensation from the insurance company were registered in Swespine. Of the 210 complications associated with these 182 claims, only 74 were listed in Swespine. The most common causes of compensated injuries (n = 139) were dural lesions (n = 40) and wound infections (n = 30). Clinical outcome based on global assessment, leg pain, disability, and quality of health was worse for patients who claimed economic compensation than for the total group of Swespine patients. INTERPRETATION: We found considerable under-reporting of complications in Swespine. Dural lesions and infections were not well recorded, although they were important reasons for problems and contributed to high levels of disability. By analyzing data from more than one source, we obtained a better understanding of the patterns of adverse events and outcomes after spine surgery. PMID- 22066565 TI - Metabolic strategies of free-living and aggregate-associated bacterial communities inferred from biologic and chemical profiles in the Black Sea suboxic zone. AB - The Black Sea is a permanently anoxic basin with a well-defined redox gradient. We combine environmental 16S rRNA gene data from clone libraries, terminal restriction fragment length polymorphisms, and V6 hypervariable region pyrosequences to provide the most detailed bacterial survey to date. Furthermore, this data set is informed by comprehensive geochemical data; using this combination of information, we put forward testable hypotheses regarding possible metabolisms of uncultured bacteria from the Black Sea's suboxic zone (microaerophily, nitrate reduction, manganese cycling, and oxidation of methane, ammonium, and sulfide). Dominant bacteria in the upper suboxic zone included members of the SAR11, SAR324, and Microthrix groups and in the deep suboxic zone included members of BS-GSO-2, Marine Group A, and SUP05. A particulate fraction (30 MUm filter) was used to distinguish between free-living and aggregate attached communities in the suboxic zone. The particulate fraction contained greater diversity of V6 tag sequences than the bulk water samples. Lentisphaera, Epsilonproteobacteria, WS3, Planctomycetes, and Deltaproteobacteria were enriched in the particulate fraction, whereas SAR11 relatives dominated the free-living fraction. On the basis of the bacterial assemblages and simple modeling, we find that in suboxic waters, the interior of sinking aggregates potentially support manganese reduction, sulfate reduction, and sulfur oxidation. PMID- 22066566 TI - Editorial. PMID- 22066567 TI - Errata. PMID- 22066568 TI - A combination of clinical and microbiological management of generalized aggressive periodontitis in primary teeth. A case report. AB - BACKGROUND: Generalized aggressive periodontitis (GAP) in primary teeth is a rare periodontal disease that occurs during or soon after eruption of the primary teeth. An association with systemic diseases is a possibility. CASE REPORT: A 4 year-old Brazilian girl presented with GAP involving the entire primary dentition. The patient and her parents and sister were subjected to microbiological testing to identify the microorganisms involved in the disease. The patient underwent tooth extraction to eradicate the disease and received a prosthesis for the restoration of masticatory function. After the permanent teeth erupted, fixed orthodontic appliances were place to restore dental arch form and occlusion. CONCLUSIONS: The results show the importance of an early diagnosis of GAP and of a multidisciplinary approach involving laboratory and clinical management to treat the disease and to restore masticatory function, providing a better quality of life for patients. PMID- 22066569 TI - Quantitative assessment of left ventricular systolic function in patients with coronary heart disease by velocity vector imaging. AB - OBJECTIVE: To assess the left ventricular (LV) longitudinal systolic function and asynchrony in patients with coronary atherosclerotic heart disease (CAD) by syngo velocity vector imaging (VVI). METHODS: Twenty-eight control subjects and 79 patients with CAD were examined, including 28 patients with myocardial infarction, 26 patients with coronary lumen stenosis <50%, and 25 patients with myocardial ischemia. According to the results of coronary arteriography and electrocardiogram (ECG), the myocardial segments of the LV of CAD patients were divided into four groups: ischemic, infarcted, nonischemic, and normal. Dynamic imaging was performed on all subjects. The systolic peak strain (Smax), systolic strain rate (SRmax), time to peak strain (PTs), and time to peak strain rate (PTsr) in every cardiac cycle were measured. RESULTS: A total of 1,253 out of 1,712 (96.5%) segments were successfully analyzed with VVI. Smax and SRmax of the ischemic and infarcted segments were impaired in CAD patients. Optimal sensitivity and specificity were obtained with strain and strain rate cutoffs of 14.08% and -0.83 s(-1) , respectively, for detecting ischemic segments and -6.65% and -0.38 s(-1) , respectively, for detecting infarcted segments. The PTs and PTsr were significantly longer in the ischemic and infarcted segments compared to those of the control group. CONCLUSIONS: Utilizing VVI, the longitudinal strain, strain rate, and peak time in CAD patients are easy to obtain and reproducible. Strain and strain rate cutoff values of abnormal myocardium are valuable for detecting ischemia and infarction. The PTs and PTsr values possibly estimate myocardium asynchrony in CAD patients. PMID- 22066570 TI - Morphine affects HIV-induced inflammatory response without influencing viral replication in human monocyte-derived macrophages. AB - Opiate-abusing individuals are in the top three risk-factor groups for HIV infection. In fact, almost 30% of HIV-infected individuals in the USA are reported to abuse opiates, highlighting the intersection of drugs of abuse with HIV/AIDS. Opiate-abusers are cognitively impaired and suffer from neurological dysfunctions that may lead to high-risk sexual behavior, poor adherence to antiretroviral regimens, and hepatitis-C virus infection. Collectively, these factors may contribute to accelerated HIV central nervous system (CNS) disease progression. To understand the role of morphine in disease progression, we sought to determine whether morphine influences HIV-induced inflammation or viral replication in human monocyte-derived macrophages (h-mdms) and MAGI cells infected with HIV and exposed to morphine. Chronic morphine exposure of HIV infected h-mdms led to significant alterations in the secretion of IL-6 and monocyte chemoattractant protein 2 (MCP-2). Morphine enhanced IL-6 secretion and blunted MCP-2 secretion from HIV-infected h-mdms. However, exposure of HIV infected h-mdms to morphine had no effect on tumor necrosis factor alpha secretion. Morphine had no effect on later stages of viral replication in HIV infected h-mdms. Morphine had a potentially additive effect on the HIV-induced production of IL-6 and delayed HIV-induced MCP-2 production. These results suggest that in HIV-infected opiate-abusers, enhanced CNS inflammation might result even when HIV disease is controlled. PMID- 22066572 TI - The role of the twin-arginine translocation pathway in Escherichia coli K1 pathogenicity in the African migratory locust, Locusta migratoria. AB - Escherichia coli K1 infection is a major cause of neonatal meningitis, with high rates of mortality and disability. Despite years of research, only a small number of factors contributing to E. coli K1 virulence have been identified. The Tat (twin-arginine translocation) protein export system is found in the cytoplasmic membrane of E. coli and is involved in the transport of folded proteins. In vivo and ex vivo models using the African migratory locust, Locusta migratoria, were employed to explore the role of Tat pathway in E. coli K1 virulence using tat deletion mutants. Groups of locusts were infected and mortality was recorded at 24-h intervals. The findings revealed that DeltatatA, DeltatatAC and Deltatat produced levels of mortality similar to wild-type E. coli K1, with >78% mortality recorded within 72 h. Bacteraemia was determined from haemolymph obtained 3 and 24 h postinfection. Again, wild-type and DeltatatA produced similar levels of bacteraemia. In contrast, DeltatatAC and Deltatat produced lower levels of bacteraemia. Following injection of bacteria into isolated head capsules ex vivo, all mutants invaded the CNS. Overall, these studies showed no evidence of involvement of the Tat pathway in locust mortality but suggest its possible role in bacteraemia. PMID- 22066571 TI - Impact of aging on pulmonary responses to acute ozone exposure in mice: role of TNFR1. AB - CONTEXT: Chamber studies in adult humans indicate reduced responses to acute ozone with increasing age. Age-related changes in TNFalpha have been observed. TNFalpha induced inflammation is predominantly mediated through TNFR1. OBJECTIVE: To examine the impact of aging on inflammatory responses to acute ozone exposure in mice and determine the role of TNFR1 in age-related differences. MATERIALS AND METHODS: Wildtype and TNFR1 deficient (TNFR1(-/-)) mice aged 7 or 39 weeks were exposed to ozone (2 ppm for 3 h). Four hours after exposure, bronchoalveolar lavage (BAL) was performed and BAL cells, cytokines, chemokines, and protein were examined. RESULTS: Ozone-induced increases in BAL neutrophils and in neutrophil chemotactic factors were lower in 39- versus 7-week-old wildtype, but not (TNFR1( /-)) mice. There was no effect of TNFR1 genotype in 7-week-old mice, but in 39 week-old mice, BAL neutrophils and BAL concentrations of MCP-1, KC, MIP-2, IL-6 and IP-10 were significantly greater following ozone exposure in TNFR1(-/-) versus wildtype mice. BAL concentrations of the soluble form of the TNFR1 receptor (sTNFR1) were substantially increased in 39-week-old versus 7-week-old mice, regardless of exposure. DISCUSSION AND CONCLUSION: The data suggest that increased levels of sTNFR1 in the lungs of the 39-week-old mice may neutralize TNFalpha and protect these older mice against ozone-induced inflammation. PMID- 22066573 TI - Hyperglycaemia emerging during general anaesthesia induces rat acute kidney injury via impaired microcirculation, augmented apoptosis and inhibited cell proliferation. AB - AIM: Major surgery under general anaesthesia frequently triggers acute kidney injury by yet unknown mechanisms. We investigated the role of anaesthesia triggered systemic hyperglycaemia in impairment of renal functioning, renal tissue injury, intra-renal Angiotensin-II synthesis and endogenous insulin production in anaesthetized rats. METHODS: Eighty-eight Sprague-Dawley rats underwent general anaesthesia for 1 h by different anaesthetic compounds. Some of the animals were either injected with high glucose, or received insulin prior to anaesthesia. Blood pressure, renal functioning estimated by cystatin-C and urea, renal perfusion evaluated by laser Doppler technique, blood glucose and insulin were surveyed. Subsequently, rat kidneys were excised, to be used for immunohistochemical examinations or preparation of renal extracts for intra-renal Angiotensin-II measurements. RESULTS: Elevated blood sugar was observed 5 min following induction of anaesthesia, concurrently with deterioration of renal functioning, drop of systemic blood pressure and decreased renal blood flow. Blood insulin concentrations positively correlated with glucose levels. Intra renal Angiotensin-II was significantly augmented. Immunohistochemical examinations demonstrated enhanced staining for pro-apoptotic proteins and negligible cell proliferation in tubular tissues. Renal damage resultant from anaesthesia-induced hyperglycaemia could be attenuated by insulin injections. Rats challenged with glucose prior to anaesthesia demonstrated cumulative hyperglycaemia, further increase in insulin secretion, drop of renal blood flow and increased apoptosis. The effects were specific, since they could not be mimicked by replacing glucose with mannose. CONCLUSION: Anaesthesia-induced hyperglycaemia affects intra-renal auto-regulation via decreased renal perfusion, thus triggering renal function deterioration and tubular injury. Increased intra renal Angiotensin-II aggravates the damage. Tight hypoglycaemic control might prevent or, at least, attenuate anaesthesia-induced renal injury. PMID- 22066574 TI - Parenting children with neurodevelopmental disorders and/or behaviour problems. AB - BACKGROUND: Parenting behaviours influence child well-being and development. However, much of the research on parenting behaviours and their correlates has focused on caregivers of healthy, typically developing children. Relatively less is known about the parenting behaviours of caregivers of children with chronic health conditions. OBJECTIVE: To examine and compare three parenting behaviours (positive interactions, consistency and ineffective parenting) among caregivers of children with neurodevelopmental disorders and/or externalizing behaviour problems, before and after accounting for child and family socio-demographic characteristics. METHODS: Participants (n= 14 226) were drawn from the National Longitudinal Survey of Children and Youth, a long-term study of Canadian children that follows their development and well-being from birth to early adulthood. Children (and their caregivers) were divided into four groups according to the presence of a neurodevelopmental disorder (NDD; n= 815), the presence of an externalizing behaviour problem (EBP; n= 1322), the presence of both conditions (BOTH; n= 452) or neither of these conditions (NEITHER; n= 11 376). RESULTS: Caregivers of children in the NEITHER group reported significantly higher positive interaction scores and lower ineffective parenting behaviours than caregivers of children in any of the other three groups. Caregivers of children in the EBP and BOTH groups reported similar levels of consistency, but significantly lower levels than caregivers of NDD or NEITHER children. These associations largely remained after accounting for child and family socio demographic characteristics, with two exceptions: caregivers' reports of positive interactions were no longer significantly associated with child's NDD and BOTH conditions. CONCLUSIONS: Parenting children with multiple health conditions can be associated with less positive, less consistent and more ineffective parenting behaviours. Understanding the factors that are associated with the challenges of caring for these children may require additional research attention. PMID- 22066575 TI - Sensitive fluorescent detection and Lewis basicity of aliphatic amines. AB - In this contribution is reported the sensitive properties of the Zn(II) Schiff base complex, 1, in dichloromethane with respect a series of primary, secondary, and tertiary aliphatic amines through the study of fluorescence enhancement upon amine coordination to the Lewis acidic Zn(II) metal center with formation of 1:1 adducts. It is found that complex 1 exhibits selectivity and nanomolar sensitivity for primary and alicyclic amines. A distinct selectivity is also observed along the series of secondary or tertiary amines, paralleling the increasing steric hindrance at the nitrogen atom. The binding interaction can be related to the Lewis basicity of the coordinating amine; thus, complex 1 represents a suitable reference Lewis acid, and estimated binding constants within the investigated amine series can be related to their relative Lewis basicity. A relative order of the Lewis basicity can be established for acyclic amines, primary > secondary > tertiary, while an inverted order, tertiary > secondary ~ primary (acyclic), is found in the case of alicyclic amines. The present approach represents a simple, suitable method to ranking the relative Lewis basicity of aliphatic amines in low-polarity, nonprotogenic solvents. PMID- 22066576 TI - Agminated, eruptive pyogenic granuloma-like lesions developing over congenital vascular stains. AB - We report three infants who developed agminated pyogenic granulomas over congenital vascular malformations, all of which had an aggressive growth pattern. There were no precipitating events such as laser therapy or surgery. Lesions were excised. PMID- 22066577 TI - Novel lanthanide-based polymeric chains and corresponding ultrafast dynamics in solution. AB - Two types of structurally related one-dimensional coordination polymers were prepared by reacting lanthanide trichloride hydrates [LnCl(3).(H(2)O)(m)] with dibenzoylmethane (Ph(2)acacH) and a base. Using cesium carbonate (Cs(2)CO(3)) and praseodymium, neodymium, samarium, or dysprosium salts yielded [Cs{Ln(Ph(2)acac)(4)}](n) (Ln = Pr (1), Nd (2), Sm (3), Dy (4)) in considerable yields. Reaction of potassium tert-butoxide (KOtBu) and the neodymium salt [NdCl(3).(H(2)O)(6)] with Ph(2)acacH resulted in [K{Nd(Ph(2)acac)(4)}](n) (5). All polymers exhibit a heterobimetallic backbone composed of alternating lanthanide and alkali metal atoms which are bridged by the Ph(2)acac ligands in a linear fashion. ESI-MS investigations on DMF solutions of 1-5 revealed a dissociation of all the five compounds upon dissolution, irrespective of the individual lanthanide and alkali metal present. Temporal profiles of changes in optical density were acquired performing pump/probe experiments with DMF solutions of 1-5 via femtosecond laser spectroscopy, highlighting a lanthanide specific relaxation dynamic. The corresponding relaxation times ranging from seven picoseconds to a few hundred picoseconds are strongly dependent on the central lanthanide atom, indicating an intramolecular energy transfer from ligands to lanthanides. This interpretation also demands efficient intersystem crossing within one to two picoseconds from the S(1) to T(1) level of the ligands. Magnetic studies show that [Cs{Dy(Ph(2)acac)(4)}](n) (4) has slow relaxation of the magnetization arising from the single Dy(3+) ions and can be described as a single-ion single molecule magnet (SMM). Below 0.5 K, hysteresis loops of the magnetization are observed, which show weak single chain magnet (SCM) behavior. PMID- 22066578 TI - Dimeric ent-kaurane diterpenoids from Isodon excisus. AB - Five new dimeric ent-kauranoids, biexcisusins A-E (1-5), were isolated from the aerial parts of Isodon excisus. The structures and relative configurations of these compounds were determined on the basis of spectroscopic data interpretation. Of these, biexcisusins C-E (3-5) are dimeric ent-kaurane diterpenoids exhibiting an unprecedented linkage through a nine-membered lactone ring between two ent-kaurane subunits. Compounds 1-5 showed no inhibitory effects on the LPS-induced production of nitric oxide in murine macrophage RAW264.7 cells, up to a dose of 50 MUM. PMID- 22066579 TI - MDM2 SNP309 polymorphism and colorectal cancer risk: appraisal of a recent meta analysis. PMID- 22066580 TI - CDH1 C-160A polymorphism and gastric cancer risk: evidence needed for clarification. PMID- 22066581 TI - Binding at birth: the newborn brain detects identity relations and sequential position in speech. AB - Breaking the linguistic code requires the extraction of at least two types of information from the speech signal: the relations between linguistic units and their sequential position. Furthermore, these different types of information need to be integrated into a coherent representation of language structure. The brain networks responsible for these abilities are well known in adults, but not in young infants. Our results show that the neural architecture underlying these abilities is operational at birth. In three optical imaging studies, we found that the newborn brain detects identity relations, as evidenced by enhanced activation in the bilateral superior temporal and left inferior frontal regions. More importantly, the newborn brain can also determine whether such identity relations hold for the initial or final positions of speech sequences, as indicated by increased activity in the inferior frontal regions, possibly Broca's area. This implies that the neural foundations of language acquisition are in place from birth. PMID- 22066582 TI - Visuo-tactile integration in personal space. AB - Integration of information across sensory modalities is enhanced when stimuli in both modalities are in the same location. This "spatial rule" of multisensory integration has been primarily studied in humans by comparing stimuli located either in the same versus opposite side of the body midline or in peripersonal versus extrapersonal space, both of which involve large, categorical differences in spatial location. Here we used psychophysics and ERPs to investigate visuo tactile integration in personal space (i.e., on the skin surface). We used the mirror box technique to manipulate the congruence of visual and tactile information about which finger on either the right or left hand had been touched. We observed clear compatibility effects for both visual and tactile judgments of which finger on the left hand had been touched. No such effects, however, were found for judgments about the right hand. ERP data showed a similar pattern. Amplitude of the vertex P200 potential was enhanced and that of the N2 was reduced for congruent visuo-tactile events on the left, but not the right, hand. Similarly, a later positivity over posterior parietal cortices (P300) showed contralateral enhancement for congruent visuo-tactile events on both the left and right hands. These results provide clear evidence for spatial constraints on visuo-tactile integration defined in personal space and also reveal clear lateralization of these effects. Furthermore, these results link these "ultraprecise" spatial constraints to processing in the right posterior parietal cortex. PMID- 22066583 TI - Effects of Delta9-tetrahydrocannabinol administration on human encoding and recall memory function: a pharmacological FMRI study. AB - Deficits in memory function are an incapacitating aspect of various psychiatric and neurological disorders. Animal studies have recently provided strong evidence for involvement of the endocannabinoid (eCB) system in memory function. Neuropsychological studies in humans have shown less convincing evidence but suggest that administration of cannabinoid substances affects encoding rather than recall of information. In this study, we examined the effects of perturbation of the eCB system on memory function during both encoding and recall. We performed a pharmacological MRI study with a placebo-controlled, crossover design, investigating the effects of Delta9-tetrahydrocannabinol (THC) inhalation on associative memory-related brain function in 13 healthy volunteers. Performance and brain activation during associative memory were assessed using a pictorial memory task, consisting of separate encoding and recall conditions. Administration of THC caused reductions in activity during encoding in the right insula, the right inferior frontal gyrus, and the left middle occipital gyrus and a network-wide increase in activity during recall, which was most prominent in bilateral cuneus and precuneus. THC administration did not affect task performance, but while during placebo recall activity significantly explained variance in performance, this effect disappeared after THC. These findings suggest eCB involvement in encoding of pictorial information. Increased precuneus activity could reflect impaired recall function, but the absence of THC effects on task performance suggests a compensatory mechanism. These results further emphasize the eCB system as a potential novel target for treatment of memory disorders and a promising target for development of new therapies to reduce memory deficits in humans. PMID- 22066584 TI - The neural underpinings of simultanagnosia: disconnecting the visuospatial attention network. AB - Because of our limited processing capacity, different elements of the visual scene compete for the allocation of processing resources. One of the most striking deficits in visual selection is simultanagnosia, a rare neuropsychological condition characterized by impaired spatial awareness of more than one object at time. To decompose the neuroanatomical substrates of the syndrome and to gain insights into the structural and functional organization of visuospatial attention, we performed a systematic evaluation of lesion patterns in a group of simultanagnosic patients compared with patients with either (i) unilateral visuospatial deficits (neglect and/or extinction) or (ii) bilateral posterior lesions without visuospatial deficits, using overlap/subtraction analyses, estimation of lesion volume, and a lesion laterality index. We next used voxel-based morphometry to assess the link between different visuospatial deficits and gray matter and white matter (WM) damage. Lesion overlap/subtraction analyses, lesion laterality index, and voxel-based morphometry measures converged to indicate that bilateral parieto-occipital WM disconnections are both distinctive and necessary to create symptoms associated with simultanagnosia. We also found that bilateral gray matter damage within the middle frontal area (BA 46), cuneus, calacarine, and parieto-occipital fissure as well as right hemisphere parietal lesions within intraparietal and postcentral gyri were associated with simultanagnosia. Further analysis of the WM based on tractography revealed associations with bilateral damage to major pathways within the visuospatial attention network, including the superior longitudinal fasciculus, the inferior fronto-occipital fasciculus, and the inferior longitudinal fasciculus. We conclude that damage to the parieto-occipital regions and the intraparietal sulcus, together, with bilateral WM disconnections within the visuosptial attention network, contribute to poor visual processing of multiple objects and the loss of processing speed characteristic of simultanagnosia. PMID- 22066585 TI - Interaction between visual- and goal-related neuronal signals on the trajectories of saccadic eye movements. AB - During natural viewing, the trajectories of saccadic eye movements often deviate dramatically from a straight-line path between objects. In human studies, saccades have been shown to deviate toward or away from salient visual distractors depending on visual- and goal-related parameters, but the neurophysiological basis for this is not well understood. Some studies suggest that deviation toward is associated with competition between simultaneously active sites within the intermediate layers of the superior colliculus (SC), a midbrain structure that integrates sensory and goal-related signals for the production of saccades. In contrast, deviation away is hypothesized to reflect a higher-level process, whereby the neural site associated with the distractor isactively suppressed via a form of endogenous, top-down inhibition. We tested this hypothesis by measuring presaccadic distractor-evoked activation of SC visuomotor neurons while monkeys performed a simple task configured specifically to induce a high degree of saccades that deviate away. In the SC, cognitive processes such as top-down expectation are represented as variation in the sustained, low-frequency presaccadic discharge. We reasoned that any inhibition at the distractor-related locus associated with saccade deviation should affect the excitability of the neuron, thereby affecting the discharge rate. We found that, although the task produced robust deviation away, there was no evidence of a relationship between saccade deviation and distractor-evoked activation outside a short perisaccadic window that began no earlier than 22 msec before saccade onset. This indicates that deviation away is not adequately explained by a form of sustained, top-down inhibition at the distractor-related locus in the SC. The results are discussed in relation to the primary sources of inhibition associated with saccadic control. PMID- 22066586 TI - Incongruent abstract stimulus-response bindings result in response interference: FMRI and EEG evidence from visual object classification priming. AB - Stimulus repetition often leads to facilitated processing, resulting in neural decreases (repetition suppression) and faster RTs (repetition priming). Such repetition-related effects have been attributed to the facilitation of repeated cognitive processes and/or the retrieval of previously encoded stimulus-response (S-R) bindings. Although previous research has dissociated these two forms of learning, their interaction in the brain is not fully understood. Utilizing the spatial and temporal resolutions of fMRI and EEG, respectively, we examined a long-lag classification priming paradigm that required response repetitions or reversals at multiple levels of response representation. We found a repetition effect in occipital/temporal cortex (fMRI) that was time-locked to stimulus onset (EEG) and robust to switches in response, together with a repetition effect in inferior pFC (fMRI) that was time-locked to response onset (EEG) and sensitive to switches in response. The response-sensitive effect occurred even when changing from object names (words) to object pictures between repetitions, suggesting that S-R bindings can code abstract representations of stimuli. Most importantly, we found evidence for interference effects when incongruent S-R bindings were retrieved, with increased neural activity in inferior pFC, demonstrating that retrieval of S-R bindings can result in facilitation or interference, depending on the congruency of response between repetitions. PMID- 22066587 TI - Somatosensory anticipatory alpha activity increases to suppress distracting input. AB - Effective processing of sensory input in daily life requires attentional selection and amplification of relevant input and, just as importantly, attenuation of irrelevant information. It has been proposed that top-down modulation of oscillatory alpha band activity (8-14 Hz) serves to allocate resources to various regions, depending on task demands. In previous work, we showed that contralateral somatosensory alpha activity decreases to facilitate processing of an anticipated target stimulus in a tactile discrimination task. In the current study, we asked whether somatosensory alpha activity is also modulated when expecting incoming distracting stimuli on the nonattended side. We hypothesized that an ipsilateral increase of alpha to suppress distracters would be required for optimal task performance. We recorded magneto-encephalography while subjects performed a tactile stimulus discrimination task where a cue directed attention either to their left or right hand. Distracters were presented simultaneously to the unattended hand. We found that alpha power contralateral to the attended hand decreased, whereas ipsilateral alpha power increased. In addition, posterior alpha power showed a general increase. Importantly, these three alpha components all contributed to discrimination performance. This study further extends the notion that alpha band activity is involved in shaping the functional architecture of the working brain by determining the engagement and disengagement of specific regions: Contralateral alpha decreases to facilitate stimulus detection, whereas ipsilateral alpha increases when active suppression of distracters is required. Importantly, the ipsilateral alpha increase is crucial for optimal task performance. PMID- 22066588 TI - Visuomotor coordination and motor representation by human temporal lobe neurons. AB - The division of cortical visual processing into distinct dorsal and ventral streams is a key concept in primate neuroscience [Goodale, M. A., & Milner, A. D. Separate visual pathways for perception and action. Trends in Neurosciences, 15, 20-25, 1992; Steele, G., Weller, R., & Cusick, C. Cortical connections of the caudal subdivision of the dorsolateral area (V4) in monkeys. Journal of Comparative Neurology, 306, 495-520, 1991]. The ventral stream is usually characterized as a "What" pathway, whereas the dorsal stream is implied in mediating spatial perception ("Where") and visually guided actions ("How"). A subpathway emerging from the dorsal stream and projecting to the medial-temporal lobe has been identified [Kravitz, D. J., Saleem, K. S., Baker, C. I., & Mishkin, M. A new neural framework for visuospatial processing. Nature Reviews Neuroscience, 12, 217-230, 2011; Cavada, C., & Goldman-Raiuc, P. S. Posterior parietal cortex in rhesus monkey: I. Parcellation of areas based on distinctive limbic and sensory cortico-cortical connections. Journal of Comparative Neurology, 287, 393-421, 1989]. The current article studies the coordination of visual information typically associated with the dorsal stream ("Where"), with planned movements, focusing on the temporal lobe. We recorded extracellular activity from 565 cells in the human medial-temporal and frontal lobes while 13 patients performed cued hand movements with visual feedback (visuomotor task), without feedback (motor task), or observed visual feedback without motor movement (visual-only task). We discovered two different neural populations in the human medial-temporal lobe. One consists of motor-like neurons representing hand position, speed or acceleration during the motor task but not during the visuomotor or visual tasks. The other is specific to the parahippocampal gyrus (an area known to process visual motion [Gur, M., & Snodderly, D. M. Direction selectivity in V1 of alert monkeys: Evidence for parallel pathways for motion processing. Journal of Physiology, 585, 383-400, 2007; Sato, N., & Nakamura, K. Visual response properties of neurons in the parahippocampal cortex of monkeys. Journal of Neurophysiology, 90, 876-886, 2003]) and encodes speed, acceleration, or direction of hand movements, but only during the visuomotor task: neither during visual-only nor during motor tasks. These findings suggest a functional basis for the anatomical subpathway between the dorsal stream and the medial temporal lobe. Similar to the recent expansion of the motor control process into the sensory cortex [Matyas, F., Sreenivasan, V., Marbach, F., Wacongne, C., Barsy, B., Mateo, C., et al. Motor control by sensory cortex. Science, 330, 1240 1243, 2010], our findings render the human medial-temporal lobe an important junction in the process of planning and execution of motor acts whether internally or externally (visually) driven. Thus, the medial-temporal lobe might serve as an integration node between the two processing streams. Our findings thus shed new light on the brain mechanisms underlying visuomotor coordination which is a crucial capacity for everyday survival, whether it is identifying and picking up food, sliding a key into a lock, driving a vehicle, or escaping a predator. PMID- 22066589 TI - An application of univariate and multivariate approaches in FMRI to quantifying the hemispheric lateralization of acoustic and linguistic processes. AB - The question of hemispheric lateralization of neural processes is one that is pertinent to a range of subdisciplines of cognitive neuroscience. Language is often assumed to be left-lateralized in the human brain, but there has been a long running debate about the underlying reasons for this. We addressed this problem with fMRI by identifying the neural responses to amplitude and spectral modulations in speech and how these interact with speech intelligibility to test previous claims for hemispheric asymmetries in acoustic and linguistic processes in speech perception. We used both univariate and multivariate analyses of the data, which enabled us to both identify the networks involved in processing these acoustic and linguistic factors and to test the significance of any apparent hemispheric asymmetries. We demonstrate bilateral activation of superior temporal cortex in response to speech-derived acoustic modulations in the absence of intelligibility. However, in a contrast of amplitude-modulated and spectrally modulated conditions that differed only in their intelligibility (where one was partially intelligible and the other unintelligible), we show a left dominant pattern of activation in STS, inferior frontal cortex, and insula. Crucially, multivariate pattern analysis showed that there were significant differences between the left and the right hemispheres only in the processing of intelligible speech. This result shows that the left hemisphere dominance in linguistic processing does not arise because of low-level, speech-derived acoustic factors and that multivariate pattern analysis provides a method for unbiased testing of hemispheric asymmetries in processing. PMID- 22066591 TI - Advancers in optical imaging in cancer research--part 2. PMID- 22066592 TI - Near infrared photonic finger imager for prostate cancer screening. AB - A portable rectal near infrared (NIR) scanning polarization imaging unit with an optical fiber-based rectal probe, designated as a Photonic Finger (PF), was designed, developed, built and tested. PF was used to image and locate the three dimensional (3D) positions of abnormal prostate tissue embedded inside normal prostate tissue. An inverse image reconstruction algorithm, namely Optical Tomography using Independent Component Analysis (OPTICA) was developed to unmix the signal from targets (cancerous tissue) embedded in a turbid media (normal tissue) in the backscattering imaging geometry. The Photonic Finger combined with OPTICA was ex vivo tested to characterize different target(s) inside different tissue medium, including cancerous prostate tissue embedded inside large pieces of normal tissue. This new developed instrument, Photonic Finger, may provide an alternative imaging technique, which is accurate, of high spatial resolution and non-or-less invasive for prostate cancers screening. PMID- 22066590 TI - Imaging of homeostatic, neoplastic, and injured tissues by HA-based probes. AB - An increase in hyaluronan (HA) synthesis, cellular uptake, and metabolism occurs during the remodeling of tissue microenvironments following injury and during disease processes such as cancer. We hypothesized that multimodality HA-based probes selectively target and detectably accumulate at sites of high HA metabolism, thus providing a flexible imaging strategy for monitoring disease and repair processes. Kinetic analyses confirmed favorable available serum levels of the probe following intravenous (i.v.) or subcutaneous (s.c.) injection. Nuclear (technetium-HA, (99m)Tc-HA, and iodine-HA, (125)I-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver ((99m)Tc-HA), breast cancer cells/xenografts (TR-HA, Gd-HA), and vascular injury ((125)I-HA, TR-HA). Targeting of HA probes to these sites appeared to result from selective HA receptor-dependent localization. Our results suggest that HA-based probes, which do not require polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues. PMID- 22066593 TI - Transrectal ultrasound-integrated spectral optical tomography of hypoxic progression of a regressing tumor in a canine prostate. AB - The objective of this study was to evaluate if transrectal optical tomography implemented at three wavelength bands for spectral detection could monitor changes of the hemoglobin oxygen saturation (StO2) in addition to those of the total hemoglobin concentration ([HbT]) in lesions of a canine prostate, including an induced tumor modeling canine prostate cancer. Near-infrared (NIR) optical tomography was integrated with ultrasound (US) for transrectal imaging. Multi spectral detection at 705_nm, 785_nm and 808_nm rendered measurements of [HbT] and StO2. Canine transmissible venereal tumor (TVT) cells were injected into the right lobe of a dog's prostate gland, which had a pre-existing cyst in the left lobe. Longitudinal assessments of the prostate were performed weekly over a 63 day duration by NIR imaging concurrent with grey-scale and Doppler US. Ultrasonography revealed a bi-lobular tumor-mass regressing from day-49 to day 63. At day-49 this tumor-mass developed a hypoxic core that became larger and more intense by day-56 and expanded further by day-63. The tumor-mass presented a strong hyper-[HbT] feature on day-56 that was inconsistent with US-visualized blood flow. Histology confirmed two necrotic TVT foci within this tumor-mass. The cyst appeared to have a large anoxic-like interior that was greater in size than its ultrasonographically delineated lesion, and a weak lesional elevation of [HbT]. On day-56, the cyst presented a strong hyper-[HbT] feature consistent with US-resolved blood flow. Histology revealed acute and chronic hemorrhage in the periphery of the cyst. The NIR imaging features of two other TVT nodules and a metastatic lymph node were evaluated retrospectively. Transrectal US-integrated spectral optical tomography seems to enable longitudinal monitoring of intra lesional oxygenation dynamics in addition to the hemoglobin content of lesions in the canine prostate. PMID- 22066594 TI - Monitoring the response to primary medical therapy for breast cancer using three- dimensional time-resolved optical mammography. AB - Primary medical therapy is used to reduce tumour size prior to surgery in women with locally advanced breast cancer. Optical tomography is a functional imaging technique using near- infrared light to produce three-dimensional breast images of tissue oxygen saturation and haemoglobin concentration. Its advantages include the ability to display quantitative physiological information, and to allow repeated scans without the hazards associated with exposure to ionising radiation. There is a need for a non-invasive functional imaging tool to evaluate response to treatment, so that non-responders can be given the opportunity to change their treatment regimen. Here, we evaluate the use of optical tomography for this purpose. Four women with newly diagnosed breast cancer who were about to undergo primary medical therapy gave informed and voluntary consent to take part in the study. Changes in physiological and optical properties within the tumour were evaluated during the course of neoadjuvant chemotherapy. Optical imaging was performed prior to treatment, after the first cycle of chemotherapy, halfway through, and on completion of chemotherapy. Images of light absorption and scatter at two wavelengths were produced, from which images of total haemoglobin concentration and oxygen saturation were derived. All patients that showed a good or complete response to treatment on MRI showed a corresponding recovery in the haemoglobin concentration images. Changes in mean tumour total haemoglobin concentration could be seen four weeks into treatment. The tumour oxygen saturation was low compared to background in three out of four patients, and also showed a return to baseline over treatment. Optical imaging of the breast is feasible during primary medical therapy and can be used to assess response to treatment over six months. PMID- 22066595 TI - Using in-vivo fluorescence imaging in personalized cancer diagnostics and therapy, an image and treat paradigm. AB - The major goal in developing drugs targeting specific tumor receptors, such as Monoclonal AntiBodies (MAB), is to make a drug compound that targets selectively the cancer-causing biomarkers, inhibits their functionality, and/or delivers the toxin specifically to the malignant cells. Recent advances in MABs show that their efficacy depends strongly on characterization of tumor biomarkers. Therefore, one of the main tasks in cancer diagnostics and treatment is to develop non-invasive in-vivo imaging techniques for detection of cancer biomarkers and monitoring their down regulation during the treatment. Such methods can potentially result in a new imaging and treatment paradigm for cancer therapy. In this article we have reviewed fluorescence imaging approaches, including those developed in our group, to detect and monitor Human Epidermal Growth Factor 2 (HER2) receptors before and during therapy. Transition of these techniques from the bench to bedside is the ultimate goal of our project. Similar approaches can be used potentially for characterization of other cancer related cell biomarkers. PMID- 22066596 TI - Feasibility of identification of gamma knife planning strategies by identification of pareto optimal gamma knife plans. AB - The use of conformity indices to optimize Gamma Knife planning is common, but does not address important tradeoffs between dose to tumor and normal tissue. Pareto analysis has been used for this purpose in other applications, but not for Gamma Knife (GK) planning. The goal of this work is to use computer models to show that Pareto analysis may be feasible for GK planning to identify dosimetric tradeoffs. We define a GK plan A to be Pareto dominant to B if the prescription isodose volume of A covers more tumor but not more normal tissue than B, or if A covers less normal tissue but not less tumor than B. A plan is Pareto optimal if it is not dominated by any other plan. Two different Pareto optimal plans represent different tradeoffs between dose to tumor and normal tissue, because neither plan dominates the other. 'GK simulator' software calculated dose distributions for GK plans, and was called repetitively by a genetic algorithm to calculate Pareto dominant plans. Three irregular tumor shapes were tested in 17 trials using various combinations of shots. The mean number of Pareto dominant plans/trial was 59 +/- 17 (sd). Different planning strategies were identified by large differences in shot positions, and 70 of the 153 coordinate plots (46%) showed differences of 5mm or more. The Pareto dominant plans dominated other nearby plans. Pareto dominant plans represent different dosimetric tradeoffs and can be systematically calculated using genetic algorithms. Automatic identification of non-intuitive planning strategies may be feasible with these methods. PMID- 22066598 TI - Rectal planning risk volume correlation with acute and late toxicity in 3 dimensional conformal radiation therapy for prostate cancer. AB - The purpose of this study was to evaluate rectum motion during 3-Dimensional conformal radiation therapy (3D-CRT) in prostate cancer patients, to derive a planning volume at risk (PRV) and to correlate the PRV dose-volume histograms (DVH) with treatment complications.This study was conducted in two phases. Initially, the PRV was defined prospectively in 50 consecutive prostate cancer patients (Group 1) who received a radical course of 3-D CRT. Then, the obtained PRV was used in the radiotherapy planning of these same 50 patients plus another 59 prostate cancer patients (Group 2) previously treated between 2004 and 2008. All these patients' data, including the rectum and PRV DVHs, were correlated to acute and late complications, according to the Common Toxicity Criteria (CTC) v4.0.The largest displacement occurred in the anterior axis. Long-term gastrointestinal (GI) complications grade >= 2 were seen in 9.2% of the cases. Factors that influenced acute GI reactions were: doses at 25% (p 5 0.011) and 40% (p 5 0.005) of the rectum volume and at 40% of the PRV (p 5 0.012). The dose at 25% of the rectum volume (p 5 0.033) and acute complications >= grade 2 (p 5 0.018) were prognostic factors for long-term complications. The PRV DVH did not correlate with late toxicity. The rectum showed a significant inter-fraction motion during 3D-CRT for prostate cancer. PRV dose correlated with acute gastrointestinal complications and may be a useful tool to predict and reduce their occurrence. PMID- 22066597 TI - Improved normal tissue sparing in head and neck radiotherapy using biological cost function based-IMRT. AB - Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50_Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry. PMID- 22066599 TI - A spatial resolution study of a new optical tomography-based polymer gel dosimetry system. AB - A spatial resolution investigation of the OCTOPUSTM-IQ scanner in combination with the new BANG3-Pro2(r) polymer gel was performed by scanning a high-contrast needle phantom. The phantom contained five thin needles (0.3_mm diameter) embedded in gel positioned in different patterns: needles were inserted (a) at 45 degrees angle from the center of the gel container, and (b) vertically along the gel axis. The non-irradiated needle phantoms were scanned at various slice spacings (0.25-1.0_mm) and for two different laser beam orientations. Optical density profiles and their full width at half maximum (FWHM) were evaluated for resolution limit. The modulation transfer function (MTF) corresponding to measured point spread function (PSF) data was calculated. With high resolution scanning mode and 0.25_mm pixel resolution, the measured PSFs at the center of the gel dosimeter have a FWHM of 0.95_mm. The MTF for the 0.25_mm reconstruction pixel size suggests that the resolution of the system is 0.5_mm or less. We also observed a progressive degradation of the vertical needle images with off-axis distance, attributable to the defocusing of the laser beam. No significant degradation was observed up to the maximum useful reconstructed image radius of 50_mm from the gel dosimeter center axis. PMID- 22066600 TI - Comparison of internal target volumes for hepatocellular carcinoma defined using 3DCT with active breathing coordinator and 4DCT. AB - The aim of this paper is to study the feasibility for determining the individual internal target volume (ITV) for hepatocellular carcinoma (HCC) using 3DCT associated with active breathing coordinator (ABC), comparing the ITVs defined by 3DCT associated with ABC and 4DCT. Thirteen patients with HCC after transarterial chemoembolization (TACE) treatment underwent 4DCT simulation and 3DCT simulation associated with ABC in free breathing (FB), end inspiration hold (EIH) and end expiration hold (EEH). The 4DCT images were sorted into 10 phases according to the respiratory cycle and labeled as CT(0), CT(10)...CT(90); and CT(MIP) (the maximum intensity projection image) was reconstructed. GTV(0), GTV(10)...GTV(90), GTV(MIP) on 4DCT, and the GTV(FB), GTV(EIH), GTV(EEH) on 3DCT were contoured. GTV(0,10...90), GTV(0) and GTV(50), GTV(EIH) and GTV(EEH) were merged into ITV(1), ITV(2) and ITV(3). The individual margins from GTV(FB) to ITV(1-3) were obtained and applied to ITV(FB) (labeled as ITV(FB-1), ITV(FB-2), ITV(FB-3)), respectively. All the target volumes were normalized by ITV(1). The volume of GTVs, ITVs and the margins were compared. There was no significant difference of diaphragm mobility between 4DCT and 3DCT (P > 0.05), nor significant difference among the volume of the GTVs. The three ITVs were larger than the GTV(MIP) (P < 0.05), but there was no significant difference among three ITVs. It's similar to the differences both in the margins of three dimensions from GTV(FB) to ITV(1-3) and in the volumes among ITV(FB-1), ITV(FB-2) and ITV(FB-3) (P > 0.05). This study shows that it's safe and feasible to determine the individual ITV for HCC using 3DCT associated with ABC in comparison with 4DCT. PMID- 22066601 TI - Imaging tumor vascularization for detection and diagnosis of breast cancer. AB - Breast cancer is one of the major causes of morbidity and mortality in western women. Current screening and diagnostic imaging modalities, like x-ray mammography and ultrasonography, focus on morphological changes of breast tissue. However, these techniques still miss some cancers and often falsely detect cancer. The sensitivity and specificity for detecting the disease can probably be improved by focusing on the consequences of tumor angiogenesis: the increased microvessel density with altered vascular characteristics. In this review, various techniques for imaging breast tumor vasculature are discussed. Dynamic contrast enhanced magnetic resonance imaging is the most-used imaging modality in this field. It has a proven high sensitivity, but a low specificity and cannot be applied in all women. Moreover, it has problems with detecting ductal carcinoma in situ (DCIS). On the contrary, contrast enhanced digital mammography can detect DCIS, but requires the use of ionizing radiation. Contrast enhanced ultrasound provides real-time information about true intravascular blood volume and flow. However, this technique still has difficulties with discriminating benign from malignant tissue. Moreover, these three imaging modalities all require the injection of contrast agents. Two relatively new techniques that do not use external contrast agents are diffuse optical imaging and photoacoustic imaging. Both visualize the increased concentration of hemoglobin in malignant tissue and thereby provide a high intrinsic contrast. PMID- 22066602 TI - Host biomarkers of clinical relevance in tuberculosis: review of gene and protein expression studies. AB - CONTEXT: Identification of clinically relevant biomarkers is required for better diagnosis, prevention and treatment of tuberculosis. OBJECTIVE: In this review, potential host biomarkers in blood or blood cells in tuberculosis were identified by a systematic approach. METHODS: A total of 55 articles were selected from PubMed and Google Scholar that analyzed gene and or protein expression in humans in active and or latent TB. Articles were scored according to certain criteria and categorized as strong or weak studies. Biomarkers reported by more than one article or by a single strong article were identified as potential biomarkers. RESULTS: Six most promising markers (IP-10, IL-6, IL-10, IL-4, FOXP3 and IL-12) were identified based on their presence in both mycobacterial antigen-stimulated and -unstimulated samples. CONCLUSIONS: With this review we hope to provide a reliable guideline for biomarker studies in tuberculosis. PMID- 22066603 TI - An indirect method to compare the reference centres for corneal measurements. AB - PURPOSE: Corneal measurements are commonly presented with respect to a specific reference centre, but the location of the reference centre on the corneal surface could vary from one diagnostic modality to another. This study aimed to develop a method for comparing reference centres used by corneal measurement systems. METHODS: An indirect method was developed to compare reference centres by making use of the pupil centre and its offset from the reference centre. Reference centres in a Scheimpflug imaging system, the Pentacam HR, and a Placido-ring corneal topography system, the ATLAS Corneal Topography System, were compared for the right and left eyes of 30 subjects. The subjects all had similar pupil sizes when measured by the two systems. Differences and correlations of the pupil centre offsets between the two systems were statistically tested and compared by Bland-Altman analyses. RESULTS: There were no significant differences in mean pupil offsets between the two systems for either the right or left eyes (p > 0.05). There were strong correlations of the pupil centre offsets between the two systems for each eye (right eye x-axis: r = 0.95, p < 0.0001; right eye y-axis: r = 0.98, p < 0.0001; left eye x-axis: r = 0.96, p < 0.0001, left eye y-axis: r = 0.93, p < 0.0001). Bland-Altman analyses revealed no significant differences in pupil centre offsets between the two systems. CONCLUSIONS: The Pentacam HR system and the ATLAS system have very similar reference centres. Thus it is possible to directly analyze data from the Pentacam HR and other instruments using the corneal vertex or the pupil centre as the reference centres due to the similarity in the reference centre settings between the two systems. PMID- 22066604 TI - A validation study of the CEMACH recommended modified early obstetric warning system (MEOWS). AB - The 2003-2005 Confidential Enquiry into Maternal and Child Health report recommended the introduction of the modified early obstetric warning system (MEOWS) in all obstetric inpatients to track maternal physiological parameters, and to aid early recognition and treatment of the acutely unwell parturient. We prospectively reviewed 676 consecutive obstetric admissions, looking at their completed MEOWS charts for triggers and their notes for evidence of morbidity. Two hundred patients (30%) triggered and 86 patients (13%) had morbidity according to our criteria, including haemorrhage (43%), hypertensive disease of pregnancy (31%) and suspected infection (20%). The MEOWS was 89% sensitive (95% CI 81-95%), 79% specific (95% CI 76-82%), with a positive predictive value 39% (95% CI 32-46%) and a negative predictive value of 98% (95% CI 96-99%). There were no admissions to the intensive care unit, cardio respiratory arrests or deaths during the study period. This study suggests that MEOWS is a useful bedside tool for predicting morbidity. Adjustment of the trigger parameters may improve positive predictive value. PMID- 22066605 TI - Self-assembling small molecules form nanofibrils that bind procaspase-3 to promote activation. AB - Modulating enzyme function with small-molecule activators, as opposed to inhibitors, offers new opportunities for drug discovery and allosteric regulation. We previously identified a compound, called 1541, from a high throughput screen (HTS) that stimulates activation of a proenzyme, procaspase-3, to generate mature caspase-3. Here we further investigate the mechanism of activation and report the surprising finding that 1541 self-assembles into nanofibrils exceeding 1 MUm in length. These particles are an unanticipated outcome from an HTS that have properties distinct from standard globular protein aggregators. Moreover, 1541 nanofibrils function as a unique biocatalytic material that activates procaspase-3 via induced proximity. These studies demonstrate a novel approach for proenzyme activation through binding to fibrils, which may mimic how procaspases are naturally processed on protein scaffolds. PMID- 22066606 TI - Human amniotic fluid stem cell preconditioning improves their regenerative potential. AB - Human amniotic fluid stem (hAFS) cells, a novel class of broadly multipotent stem cells that share characteristics of both embryonic and adult stem cells, have been regarded as promising candidate for cell therapy. Taking advantage by the well-established murine model of acute kidney injury (AKI), we studied the proregenerative effect of hAFS cells in immunodeficient mice injected with the nephrotoxic drug cisplatin. Infusion of hAFS cells in cisplatin mice improved renal function and limited tubular damage, although not to control level, and prolonged animal survival. Human AFS cells engrafted injured kidney predominantly in peritubular region without acquiring tubular epithelial markers. Human AFS cells exerted antiapoptotic effect, activated Akt, and stimulated proliferation of tubular cells possibly via local release of factors, including interleukin-6, vascular endothelial growth factor, and stromal cell-derived factor-1, which we documented in vitro to be produced by hAFS cells. The therapeutic potential of hAFS cells was enhanced by cell pretreatment with glial cell line-derived neurotrophic factor (GDNF), which markedly ameliorated renal function and tubular injury by increasing stem cell homing to the tubulointerstitial compartment. By in vitro studies, GDNF increased hAFS cell production of growth factors, motility, and expression of receptors involved in cell homing and survival. These findings indicate that hAFS cells can promote functional recovery and contribute to renal regeneration in AKI mice via local production of mitogenic and prosurvival factors. The effects of hAFS cells can be remarkably enhanced by GDNF preconditioning. PMID- 22066607 TI - Speckle tracking global strain rate E/E' predicts LV filling pressure more accurately than traditional tissue Doppler E/E'. AB - BACKGROUND: The ratio of early diastolic transmitral flow velocity (E) to tissue Doppler (TD) mitral annular early diastolic velocity (E/E'(VEL-TD)) has been widely used for the noninvasive assessment of LV diastolic filling pressures. However, it has been reported that E/E'(VEL-TD) is not accurate particularly when being applied to patients with advanced heart failure. METHODS: Fifty-six ICU patients with decompensated heart failure underwent simultaneous echocardiography and PCWP measurements. Patients with elevated PCWP (n = 41) were compared with patients normal PCWP (n = 15) as well as age-matched healthy controls (n = 32). In the apical 4-chamber view, the ratio of E to speckle tracking (ST) mitral annular velocity (E/E'(VEL-ST)) and early diastolic global LV longitudinal strain rate (E/E'(SR-ST)) were evaluated as new surrogate markers of elevated PCWP. RESULTS: Correlations with PCWP were observed for speckle tracking derived E/E'(VEL-ST) (r = 0.40,P = 0.002) and E/E'(SR-ST) (r = 0.56, P < 0.001), although the traditional E/E'(VEL-TD) did not show a significant correlation (r = 0.23, P = 0.082). Compared with controls, patients with elevated PCWP had significant increases in all variables. The best cutoff values and diagnostic accuracies for identifying elevated PCWP were E/E'(VEL-TD) >12 (Sensitivity/Specificity/area under the ROC curve: 0.58/0.90/0.78), E/E'(VEL-ST) > 14 (0.60/0.85/0.80), and E/E'(SR-ST) > 93 (0.80/0.88/0.89). CONCLUSION: Speckle tracking derived E/E'(SR ST) may be a robust surrogate marker of elevated LV filling pressure. In ICU patients, E/E'(SR-ST) showed better correlation with PCWP and higher diagnostic accuracy than the tissue Doppler approach. PMID- 22066608 TI - Comparison of 16S rRNA and protein-coding genes as molecular markers for assessing microbial diversity (Bacteria and Archaea) in ecosystems. AB - PCR amplification of the rRNA gene is the most popular method for assessing microbial diversity. However, this molecular marker is often present in multiple copies in cells presenting, in addition, an intragenomic heterogeneity. In this context, housekeeping genes may be used as taxonomic markers for ecological studies. However, the efficiency of these protein-coding genes compared to 16S rRNA genes has not been tested on environmental data. For this purpose, five protein marker genes for which primer sets are available, were selected (rplB, pyrG, fusA, leuS and rpoB) and compared with 16S rRNA gene results from PCR amplification or metagenomic data from aquatic ecosystems. Analysis of the major groups found in these ecosystems, such as Actinobacteria, Bacteroides, Proteobacteria and Cyanobacteria, showed good agreement between the protein markers and the results given by 16S rRNA genes from metagenomic reads. However, with the markers it was possible to detect minor groups among the microbial assemblages, providing more details compared to 16S rRNA results from PCR amplification. In addition, the use of a set of protein markers made it possible to deduce a mean copy number of rRNA operons. This average estimate is essentially lower than the one estimated in sequenced genomes. PMID- 22066609 TI - End-of-life care pathways as tools to promote and support a good death: a critical commentary. AB - This paper calls into question whether and how end-of-life care pathways facilitate the accomplishment of a 'good death'. Achieving a 'good death' is a prominent social and political priority and an ideal which underpins the philosophy of hospice and palliative care. End-of-life care pathways have been devised to enhance the care of imminently dying patients and their families across care settings and thereby facilitate the accomplishment of a 'good death'. These pathways have been enthusiastically adopted and are now recommended by governments in the UK as 'best practice' templates for end-of-life care. However, the literature reveals that the 'good death' is a nebulous, fluid concept. Moreover, concerns have been articulated regarding the efficacy of care pathways in terms of their impact on patient care and close analysis of two prominent end of-life pathways reveals how biomedical aspects of care are privileged. Nonetheless drawing on a diverse range of evidence the literature indicates that end-of-life care pathways may facilitate a certain type of 'good death' and one which is associated with the dying process and framed within biomedicine. PMID- 22066610 TI - The treatment of hernias. PMID- 22066612 TI - Knee joint function, meniscal disease, and osteoarthritis. PMID- 22066611 TI - Diagnosis and treatment of porto-systemic shunts. PMID- 22066613 TI - Neural regulation of swallowing in the dog. PMID- 22066614 TI - Dyspnea: How to solve the problem. PMID- 22066615 TI - An update in dentistry. PMID- 22066616 TI - Abdominal drainage in ten dogs with septic peritonitis. PMID- 22066617 TI - Diagnosis and treatment of gastric disease. PMID- 22066618 TI - Feline asthma syndrome. PMID- 22066619 TI - Cowpox in cats and man. PMID- 22066620 TI - Growth hormone: Its clinical relevance. PMID- 22066621 TI - The differential diagnosis of polyuria/polydipsia in dogs. PMID- 22066622 TI - Variable structures of mitochondrial DNA in dogs. PMID- 22066623 TI - FIP, easy to diagnose? PMID- 22066624 TI - Cytostatic treatment in veterinary medicine. PMID- 22066626 TI - Diagnostic imaging in dogs: Radiography, ultrasonography, and computed tomography for examination of the abdomen. PMID- 22066625 TI - Diagnosis of cardiac disease. PMID- 22066627 TI - Basic principles of thoracic radiography. PMID- 22066628 TI - Arthroscopy in the diagnosis and treatment of front leg lameness. PMID- 22066629 TI - The use of iohexol to measure glomerular filtration rate in the dog. PMID- 22066630 TI - The skin in systemic disease. PMID- 22066631 TI - Skin disorders in cats. PMID- 22066632 TI - Diagnosis and treatment of conjunctival and corneal diseases. PMID- 22066633 TI - Retinal diseases: An update. PMID- 22066634 TI - The role of tonometry in the clinical management of the glaucomas in companion animals. PMID- 22066635 TI - Eye lesions in Turkish dancing bears. PMID- 22066636 TI - Clinical, electrophysiological, and morphological findings in a case of neuronal ceroid lipofuscinosis in The Polish Owczarek Nizinny (PON) dog. PMID- 22066637 TI - Rod dysplasia and early retinal degeneration in a young Briard Sheepdog. PMID- 22066638 TI - Polymerase chain reaction: A revolution in diagnosis of ocular Leishmaniosis? PMID- 22066639 TI - Cataracts in rapidly growing farm raised Atlantic salmon (Salmo Salar). PMID- 22066640 TI - Changing the way we practice: How to thrive and not just survive in veterinary medicine. PMID- 22066641 TI - Diseases of the respiratory tract in psittacine birds. PMID- 22066642 TI - The nutritional requirements of ornamental fish. PMID- 22066644 TI - Seek and find in the literature. PMID- 22066646 TI - Photomedicine and LLLT Literature Watch. PMID- 22066645 TI - Ultra-conservative minimally invasive surgery (UCMIS) with pulsed non-Gaussian CO(2) laser beams focused through the shortest possible focal length. AB - OBJECTIVE: This article describes a mathematical approach to identifying the absolute shortest laser optical focusing head f(min) associated with the smallest not-to-exceed ablative crater radius and depth to be used during ultra conservative minimally invasive surgery (UCMIS) procedures with pulsed CO(2) lasers. This value is important because it allows forecasting the micro-boundary ablative conditions of a laser device implemented in the operating room (OR) in conjunction with minimally invasive tools. The primary goals of reducing the invasive character of an operation, and the associated risks of unwanted lateral tissue damage during surgery, are the key objectives of MIS protocols. BACKGROUND DATA: Currently, the data available in the literature do not report any numerical value of a critical focal length and its spot size that produce the smallest ablations. This would help to further improve the overall quality of the MIS protocols via endoscopic scalpels to deliver minimal ablative energy on the irradiated tissue. METHODS: Several mathematical software routines have been used in parallel to handle all the complex numerical calculations needed to extrapolate f(min) by using the crater, the crater depth acceleration, and speed coupled with the relaxation time ?r of polymethyl methacrylate (PMMA) and other time-related parameters. RESULTS: The minimal focal length value f(min)=0.013? for a TEM(22) laser beam profile can be used for reference in UCMIS procedures using commercially available pulsed CO2 lasers at the wavelength of 10.6??m. No laser thermoablation of compact PMMA samples is possible below f(min) while delivering I(min)=7.6?mW on its spot. Gaussian beams showing TEM00 profile need longer focal lengths for the same minimally ablated volume. Suggestions about the calibration requirements for such a lens are presented. More investigations are needed to validate the whole procedure before any preliminary surgical utilization can be considered. PMID- 22066647 TI - Sublingual vaccination with fusion protein consisting of the functional domain of hemagglutinin A of Porphyromonas gingivalis and Escherichia coli maltose-binding protein elicits protective immunity in the oral cavity. AB - This study demonstrated that sublingual immunization with a fusion protein, 25k hagA-MBP, which consists of a 25-kDa antigenic region of hemagglutinin A purified from Porphyromonas gingivalis fused to maltose-binding protein (MBP) originating from Escherichia coli as an adjuvant, elicited protective immune responses. Immunization with 25k-hagA-MBP induced high levels of antigen-specific serum IgG and IgA, as well as salivary IgA. High level titers of serum IgG and IgA were also induced for almost 1 year. In an IgG subclass analysis, sublingual immunization with 25k-hagA-MBP induced both IgG1 and IgG2b antibody responses. Additionally, numerous antigen-specific IgA antibody-forming cells were detected from the salivary gland 7 days after the final immunization. Mononuclear cells isolated from submandibular lymph nodes (SMLs) showed significant levels of proliferation upon restimulation with 25k-hagA-MBP. An analysis of cytokine responses showed that antigen-specific mononuclear cells isolated from SMLs produced significantly high levels of IL-4, IFN-gamma, and TGF-beta. These results indicate that sublingual immunization with 25k-hagA-MBP induces efficient protective immunity against P. gingivalis infection in the oral cavity via Th1 type and Th2-type cytokine production. PMID- 22066648 TI - Tracheal aspirate gene expression in preterm newborns and development of bronchopulmonary dysplasia. AB - BACKGROUND: Bronchopulmonary dysplasia (BPD) occurs in association with prenatal conditions predisposing infants to inflammation and remodeling of the premature lungs. Because of the lack of useful biomarkers for BPD, the gene expression of tracheal aspirate fluid (TAF) cells in premature infants was analyzed. METHODS: Of 148 consecutive patients, 26 preterm infants (gestational age <34 weeks) were enrolled, who underwent assisted ventilation at birth for respiratory failure. Patients with congenital disorders were excluded. Half of these infants developed BPD. Interleukin (IL)-10, interferon (IFN)-gamma, transforming growth factor (TGF)-beta1, and platelet-derived growth factor (PDGF)-B mRNA of TAF cells were quantified on real-time polymerase chain reaction. RESULTS: IL-10 (P < 0.01) and IFN-gamma (P= 0.03) but not TGF-beta1 or PDGF-B mRNA levels at birth were higher in BPD than in non-BPD infants. IL-10 expression differentiated BPD with the highest sensitivity (92%) and specificity (77%). IL-10 levels correlated with TGF beta1 (P= 0.03) and IFN-gamma (P= 0.01), but not with PDGF-B levels. When BPD infants were classified according to comorbidity (group 1, six patients who suffered respiratory distress syndrome [RDS] but not chorioamnionitis [CAM]; group 2, five patients who had CAM but not RDS), PDGF-B levels were higher in group 2 (P= 0.01). High IL-10 expression was selected as a risk factor for BPD in infants who had CAM but not RDS (P= 0.01), although prolonged oxygen therapy was the most sensitive indicator for BPD (P < 0.01) on multivariate analysis. CONCLUSIONS: High IL-10 expression in TAF cells at birth could predict the evolution of BPD, but with less impact than oxygen requirement. PDGF might play a different role in the inflammatory process of premature lungs. PMID- 22066649 TI - The 2007-2010 Q fever epidemic in The Netherlands: characteristics of notified acute Q fever patients and the association with dairy goat farming. AB - We describe the Q fever epidemic in the Netherlands with emphasis on the epidemiological characteristics of acute Q fever patients and the association with veterinary factors. Data from 3264 notifications for acute Q fever in the period from 2007 through 2009 were analysed. The patients most affected were men, smokers and persons aged 40-60 years. Pneumonia was the most common clinical presentation (62% in 2007 and 2008). Only 3.2% of the patients were working in the agriculture sector and 0.5% in the meat-processing industry including abattoirs. Dairy goat farms with Coxiella burnetii-induced abortion waves were mainly located in the same area where human cases occurred. Airborne transmission of contaminated dust particles from commercial dairy goat farms in densely populated areas has probably caused this epidemic. In 2010, there was a sharp decline in the number of notified cases following the implementation of control measures on dairy goat and sheep farms such as vaccination, hygiene measures and culling of pregnant animals on infected farms. In combination with a rise in the human population with antibodies against C. burnetii, these have most likely ended the outbreak. Development of chronic Q fever in infected patients remains an important problem for years to come. PMID- 22066650 TI - Swedish nursing and medical students' high vaccination adherence during the influenza A (H1N1) pandemic 2009: insights for pandemic preparedness. AB - The aim of this study was to analyze Swedish health science student decision making regarding vaccination against pandemic influenza during a national mass vaccination campaign. A questionnaire was distributed to 430 students during the influenza A (H1N1) pandemic in 2009. The data from medical and nursing students were compared and a multiple logistic regression model was applied to identify items independently associated with the decision to be vaccinated. The overall survey response rate was 90%. More medical (93.2%) than nursing students (84.8%) reported that they had received the vaccine (p < 0.01). Only the perception that benefits can outweigh possible side effects was significantly (p < 0.001) associated with the decision to get vaccinated. We recommend that, during pandemics, health science universities focus vaccination information for students on objective risk communication. It should be taken into account that the pandemic information provided by authorities to the general public also affects health care students. PMID- 22066653 TI - Shyness in late childhood: relations with attributional styles and self-esteem. AB - BACKGROUND: Shyness in late childhood is related to social and psychological problems. The present study examined the relations among shyness, attributional styles and self-esteem. It was hypothesized that self-esteem mediated the effects of attributional styles on shyness. METHODS: Self-reported data on degree of shyness, attributional styles and self-esteem were obtained from 326 Chinese children with mean age of 10.85 years. RESULTS: It was found that positive attributional styles predicted shyness in the negative direction and the effects were fully mediated by self-esteem, and negative attributional styles predicted shyness in the positive direction both directly and through self-esteem. CONCLUSION: The results imply that how children attribute positive and negative outcomes affect both self-esteem and shyness. It is suggested that practitioners should conduct attribution-retraining workshops for shy children and help teachers and parents learn how to mitigate negative attributional style and foster positive attributional styles in children. PMID- 22066654 TI - Phenomenological kinetics of the thermal decomposition of sodium hydrogencarbonate. AB - Aiming to find rigorous understanding and novel features for their potential applications, the physico-geometrical kinetics of the thermal decomposition of sodium hydrogencarbonate (SHC) was investigated by focusing on the phenomenological events taking place on a single crystalline particle during the course of the reaction. The overall kinetics evaluated by systematic measurements of the kinetic rate data by thermogravimetry under carefully controlled conditions were interpreted in association with the morphological studies on the precursory reaction, mechanism of surface reaction, structure of the surface product layer, diffusion path of evolved gases, crystal growth of the solid product, and so on. The precursory reaction was identified as the decomposition of impurity, taking place at the boundary between the surface of the SHC crystal and the adhesive small SHC particles deposited on the surface. In flowing dry N(2), the thermal decomposition of SHC proceeds by two-dimensional shrinkage of the reaction interface controlled by chemical reaction with the apparent activation energy of about 100 kJ mol(-1), after rapid completion of the surface reaction and formation of porous surface product layer. Atmospheric CO(2) and water vapor influence differently on the overall kinetics of the thermal decomposition of SHC. Added gas phase of CO(2) slightly inhibits the overall rate because of the increasing contribution of the surface reaction. Under higher water vapor pressure, the physico-geometrical mechanism of the surface reaction changes drastically, indicating the preliminary reformation of reactant surface and the formation of needle crystals of solid product on the surface. The mechanistic change and extended contribution of the surface reaction result in the deceleration of the surface reaction and acceleration of the established reaction. PMID- 22066655 TI - Erythema dyschromicum perstans in a Japanese child. AB - Erythema dyschromicum perstans (EDP) is asymptomatic slate-gray to blue-brown macules. Idiopathic eruptive macular pigmentation is asymptomatic brown nonconfluent macules. We describe electron microscopic studies of a 9-year-old Japanese girl with EDP. The ultrastructural figures indicated that the production of immature, small, irregular-shaped melanosomes in melanocytes and peripheral localization of melanosomes in keratinocytes caused the clinical appearance of EDP. The ultrastructural evidence distinguishes EDP from idiopathic eruptive macular pigmentation and suggests a distinct pathogenesis of the disease. PMID- 22066656 TI - Thiocyanate linkage isomerism in a ruthenium polypyridyl complex. AB - Ruthenium polypyridyl complexes have seen extensive use in solar energy applications. One of the most efficient dye-sensitized solar cells produced to date employs the dye-sensitizer N719, a ruthenium polypyridyl thiocyanate complex. Thiocyanate complexes are typically present as an inseparable mixture of N-bound and S-bound linkage isomers. Here we report the synthesis of a new complex, [Ru(terpy)(tbbpy)SCN][SbF(6)] (terpy = 2,2';6',2''-terpyridine, tbbpy = 4,4'-di-tert-butyl-2,2'-bipyridine), as a mixture of N-bound and S-bound thiocyanate linkage isomers that can be separated based on their relative solubility in ethanol. Both isomers have been characterized spectroscopically and by X-ray crystallography. At elevated temperatures the isomers equilibrate, the product being significantly enriched in the more thermodynamically stable N-bound form. Density functional theory analysis supports our experimental observation that the N-bound isomer is thermodynamically preferred, and provides insight into the isomerization mechanism. PMID- 22066657 TI - Culture change is not easy... But it can be done. PMID- 22066658 TI - CBT-pharmacotherapy combo lessens pediatric OCD symptoms. PMID- 22066662 TI - The 12-month outcome of three consecutive monthly intravitreal injections of ranibizumab for myopic choroidal neovascularization. AB - PURPOSE: The aim of this study was to evaluate the 12-month outcomes, efficacy, and safety of three consecutive monthly intravitreal ranibizumab injections for myopic choroidal neovascularization (CNV). METHODS: We retrospectively reviewed the medical records of 25 consecutive eyes that received a loading dose of three consecutive monthly intravitreal injections of ranibizumab for myopic CNV between February, 2008, and March, 2010, with a follow-up of 12 months. Eyes with persistent or recurrent CNV after 3 months received additional ranibizumab injections as needed. Patients' demographic data, best corrected visual acuity (BCVA), CNV findings on fluorescent angiography (FAG), central macular thickness (CMT) on optical coherence tomography (OCT), total number of treatments, and complications were recorded. RESULTS: Mean baseline BCVA was 0.73 logarithm of the minimum angle of resolution (logMAR) (standard deviation [SD] 0.63), and improved significantly to 0.42 logMAR (SD 0.43) at 1 month, 0.38 logMAR (SD 0.47) at 2 months, 0.34 logMAR (SD 0.43) at 3 months, and 0.34 logMAR (SD 0.40) at 12 months (all P<0.001, Wilcoxon signed-rank test). The average number of injections was 3.44 (SD 0.92). At 12 months, mean improvement was 2.88 lines (SD 2.35), and 20 eyes (80%) showed a gain of at least one line after treatment. At 3 months, OCT showed significant reduction in CMT (P=0.012, two-tailed t-test), and FAG showed significant reduction of mean CNV size from 0.3 (SD 0.16) to 0.19 (SD 0.12) disc area (P=0.007, two-tailed t-test). No angiographic leakage was evident at 3 months in 21 eyes (84%); four eyes (16%) required additional injections for persistent leakage. Two eyes (8%) had recurrent CNV during follow-up and required retreatment. No complications were noted after treatment. CONCLUSIONS: An initial loading dose of three ranibizumab injections is safe and effective in treating myopic CNV, with visual improvement maintained over 12 months. PMID- 22066663 TI - Biophysical properties and supramolecular structure of self-assembled liposome/epsilon-peptide/DNA nanoparticles: correlation with gene delivery. AB - Using solid-phase synthesis, lysine can be oligomerized by a reaction of the peptide carboxylate with the epsilon-amino group to produce nontoxic, biodegradable cationic peptides, epsilon-oligo(L-lysines). Here alpha-substituted derivatives of such epsilon-oligo(L-lysines) containing arginine and histidine in the side chain were tested as vectors for in vitro gene delivery. Combination of epsilon-oligolysines with the cationic lipid DOTAP and plasmid DNA resulted in transfection efficiency exceeding that of DOTAP alone, without significant increase in cytotoxicity. Synchrotron small-angle X-ray scattering studies revealed self-assembly of the DOTAP, epsilon-oligolysines, and DNA to ordered lamellar complexes. High transfection efficiency of the nanoparticles correlates with increase in zeta potential above +20 mV and requires particle size to be below 500 nm. The synergistic effect of branched epsilon-oligolysines and DOTAP in gene delivery can be explained by the increase in surface charge and by the supramolecular structure of the DOTAP/epsilon-oligolysine/DNA nanoparticles. PMID- 22066664 TI - Romidepsin: a guide to its clinical use in cutaneous T-cell lymphoma. AB - Intravenous romidepsin (Istodax(r)), a histone deacetylase inhibitor, is indicated in the US for the treatment of cutaneous T-cell lymphoma (CTCL) in adults who have received at least one prior systemic therapy. In two noncomparative trials in adults with relapsed, refractory, and/or advanced CTCL, romidepsin was associated with an overall response (i.e. complete or partial response) rate of 34% and 35%, and a complete response rate of 6% (in both trials). Romidepsin had an acceptable tolerability profile, with the most common grade 3 or 4 adverse events considered at least possibly related to romidepsin being hematologic or asthenic in nature. PMID- 22066665 TI - Bone mineral density and genetic markers involved in three connected pathways (focal adhesion, actin cytoskeleton regulation and cell cycle): the CUMAGAS-BMD information system. AB - The focal adhesion, the actin cytoskeleton and cell-cycle are connected pathways and their genes are implicated in the pathogenesis of low BMD. Data from 211 studies that investigated the association between BMD and gene variants involved in these pathways were catalogued in a web-based information system and analyzed. In individual studies, significant association was found for 16 variants in lumbar spine, 11 in femoral neck and 5 in hip. In meta-analysis, significant results were shown for the variants COL1A1 rs1800012 (in lumbar spine and femoral neck), COL1A1 rs1107946 (in lumbar spine), TGFB1 rs1982073 (in femoral neck and hip) and TGFB1 rs1800469 (in lumbar spine). PMID- 22066666 TI - Making a point through qualitative research. PMID- 22066668 TI - Intraoperative transesophageal echocardiographic imaging of double valve repair for aortic and mitral stenosis. AB - An intraoperative echocardiographic evaluation to determine the feasibility and adequacy of the valve repair procedure is crucial for a successful repair. However, aortic valve repair in severe aortic stenosis (AS) is very limited and, consequently, its intraoperative echocardiographic evaluation has not been described well. Here, we describe an intraoperative transesophageal echocardiographic evaluation of a double-valve repair procedure for a patient with severe AS, moderate aortic insufficiency, and severe mitral stenosis. PMID- 22066669 TI - Unveiling the transcriptional features associated with coccolithovirus infection of natural Emiliania huxleyi blooms. AB - Lytic viruses have been implicated in the massive cellular lysis observed during algal blooms, through which they assume a prominent role in oceanic carbon and nutrient flows. Despite their impact on biogeochemical cycling, the transcriptional dynamics of these important oceanic events is still poorly understood. Here, we employ an oligonucleotide microarray to monitor host (Emiliania huxleyi) and virus (coccolithovirus) transcriptomic features during the course of E. huxleyi blooms induced in seawater-based mesocosm enclosures. Host bloom development and subsequent coccolithovirus infection was associated with a major shift in transcriptional profile. In addition to the expected metabolic requirements typically associated with viral infection (amino acid and nucleotide metabolism, as well as transcription- and replication-associated functions), the results strongly suggest that the manipulation of lipid metabolism plays a fundamental role during host-virus interaction. The results herein reveal the scale, so far massively underestimated, of the transcriptional domination that occurs during coccolithovirus infection in the natural environment. PMID- 22066671 TI - Editorial. PMID- 22066672 TI - European veterinary dissertations. PMID- 22066670 TI - Association of distress symptoms and use of complementary medicine among patients with cancer. AB - AIMS AND OBJECTIVES: The aim of this study was to investigate the association between distress symptoms and the types of complementary and alternative medicine use in patients with cancer. BACKGROUND: Patients diagnosed with cancer have increasingly turned to the use of complementary and alternative medicine to manage its symptoms and cope with the side effects of conventional treatment. DESIGN: A descriptive cross-sectional study. METHODS: A face-to-face interview using a structured questionnaire was conducted with 208 outpatients at a medical centre in central Taiwan. The questionnaire included questions on socio demographic information, disease specifics, distress symptoms and complementary and alternative medicine usage in the past 12 months. Logistic regression analysis was used to assess the association between distress symptoms and the use of different complementary and alternative medicine modalities. RESULTS: A total of 165 (79.3%) patients reported use of at least one complementary and alternative medicine modality during the past 12 months. Complementary and alternative medicine users and non-users were not significantly different in age, sex, marital status, education level, religious affiliation and disease-related variables. Fatigue (66.8%) was the most frequently reported symptoms and was significantly associated with complementary and alternative medicine use (OR = 14.11, p = 0.001). Regarding specific complementary and alternative medicine modalities, chanting and enzyme therapy were found to be associated with 13 (68.4%) of the 19 distress symptoms. CONCLUSIONS: There was no association between complementary and alternative medicine use and demographic or disease related variables. Complementary and alternative medicine was widely used by patients with cancer, and symptom of fatigue was most strongly associated with complementary and alternative medicine use. Chanting and enzyme therapy were the two most frequently used complementary and alternative medicine modalities that were significantly associated with the 19 distress symptoms. RELEVANCE TO CLINICAL PRACTICE: Health care providers should ask their patients about their complementary and alternative medicine use to avoid possible adverse interactions between conventional treatment and complementary and alternative medicine interventions, in particular, those remedies that are likely to interact with cancer medications. PMID- 22066673 TI - Development of an assay for rapid detection and quantification of Verticillium dahliae in soil. AB - ABSTRACT Verticillium dahliae is responsible for Verticillium wilt on a wide range of hosts, including strawberry, on which low soil inoculum densities can cause significant crop loss. Determination of inoculum density is currently done by soil plating but this can take 6 to 8 weeks to complete and delay the grower's ability to make planting decisions. To provide a faster means for estimating pathogen populations in the soil, a multiplexed TaqMan real-time polymerase chain reaction (PCR) assay based on the ribosomal DNA (rDNA) intergenic spacer (IGS) was developed for V. dahliae. The assay was specific for V. dahliae and included an internal control for evaluation of inhibition due to the presence of PCR inhibitors in DNA extracted from soil samples. An excellent correlation was observed in regression analysis (R(2) = 0.96) between real-time PCR results and inoculum densities determined by soil plating in a range of field soils with pathogen densities as low as 1 to 2 microsclerotia/g of soil. Variation in copy number of the rDNA was also evaluated among isolates by SYBR Green real-time PCR amplification of the V. dahliae-specific amplicon compared with amplification of several single-copy genes and was estimated to range from ~24 to 73 copies per haploid genome, which translated into possible differences in results among isolates of ~1.8 cycle thresholds. Analysis of the variation in results of V. dahliae quantification among extractions of the same soil sample indicated that assaying four replicate DNA extractions for each field sample would provide accurate results. A TaqMan assay also was developed to help identify colonies of V. tricorpus on soil plates. PMID- 22066675 TI - Generation and envelope protein analysis of internalization defective Brucella abortus mutants in professional phagocytes, RAW 264.7. AB - Brucella abortus is a facultative intracellular bacteria that replicates within a macrophage without producing any classical virulence factors. It can become internalized to cells by zipper-like and/or swimming internalization mechanisms. However, the bacterial proteins involved in internalization remain unclear. To define these bacterial proteins, random insertion mutants of B. abortus were generated by the Tn5 transposome complexes. In all, 132 mutants were screened, cellular internalization-defective mutants were selected, and these genomic and envelope proteomic features were identified. The transposon insertion sites were ccmC,ppk and BruAb2_0168 for the mutant C10, C29 and D7, respectively. Mutant C10 showed a deficiency in internalization without any changes in expression of the cell envelope proteins; however, mutant C29 showed a reduced expression of OMP25, and a mutant D7 also showed reduced expression of OMP25, OMP28 and Porin2b. These results suggest OMP25 is not an essential factor, but might be involved in host cellular internalization. We identified the ppk gene and BruAb2_0168 locus which are associated to expression of OMP25, OMP28 and Porin2b as well as pleiotropic effects of ccmC gene. PMID- 22066674 TI - Mitochondrial haplotype analysis for differentiation of isolates of Phytophthora cinnamomi. AB - Although Phytophthora cinnamomi is heterothallic, there are few instances of successful crossing in laboratory experiments, and analysis of field populations indicates a clonally reproducing population. In the absence of sexual recombination, the ability to monitor mitochondrial haplotypes may provide an additional tool for identification of clonal isolates and analysis of population structure. To determine mitochondrial haplotypes for this species, seven mitochondrial loci spanning a total of 6,961 bp were sequenced for 62 isolates representing a geographically diverse collection of isolates with A1 and A2 mating type. Three of the regions were primarily intergenic regions between trnG and rns, rns and nad3, and nad6 and cox1, while the remaining loci spanned cox2, nad9, rps10, and secY coding regions and some of the flanking spacer regions. In total, 45 mitochondrial haplotypes were identified (75% of the total isolates examined) with differences due to single-nucleotide polymorphisms (SNPs, totaling 152 bp) and length mutations (17 indels >2 bp representing a total of 910 bp in length). SNPs were the predominate mutation in the four coding regions and their flanking intergenic regions, while both SNPs and length mutations were observed in the three primarily intergenic regions. Some of the length mutations in these regions were due to addition or loss of unique sequences while others were due to variable numbers of subrepeats (in the trnG-rns region, there were 3 to 12 copies of a 24-bp subrepeat sequence that differentiated 17 haplotypes). Network analysis of the haplotypes identified eight primary clades, with the most divergent clade representing primarily A1 isolates collected from Papua New Guinea. The isolate grouping in the network corresponded to mating type and previously published isozyme classifications, with three exceptions: a haplotype representing an A1 mating type (H29) was placed well within the A2 mating type haplotype grouping, one haplotype (H26) had isolates with two isozyme classifications, and one isozyme group was represented on separate network clades, suggesting that recombination has occurred in the past. Among the 62 isolates examined, several examples were identified of isolates recovered from different geographic regions having the same mitochondrial haplotype, suggesting movement of isolates via plant material. Analysis of the data set to determine whether fewer loci could be sequenced to classify haplotypes indicated that the trnG-rns and rns-nad6 loci would classify 87% of the haplotypes identified in this study, while additional sequencing of the nad9 or secY loci would further differentiate the remaining six haplotypes. Based on conservation of gene order in Phytophthora spp., the trnG-rns locus should be useful for mitochondrial haplotype classification in other species, as should the cox2, nad9, rps10, and secY loci. However, the rns-nad3 and nad6-cox1 loci span regions that can have a different gene order in some Phytophthora spp. PMID- 22066676 TI - Colocalization of Porphyromonas gingivalis with CD4+ T cells in periodontal disease. AB - Porphyromonas gingivalis, an anaerobic, asaccharolytic gram-negative bacterium, is a causative agent in chronic periodontitis. It has many virulence factors that facilitate infection of the gingiva, but little is known about the local immune cells that respond to this bacterium. The aims of this study were to quantify P. gingivalis in gingival biopsies from patients with periodontitis using laser capture microdissection (LCM) plus qRT-PCR and to determine the phenotype of immune cells associated with the bacteria using immunofluorescence. The presence of P. gingivalis was confirmed in periodontitis gingival tissue from 10 patients, and differences in bacterial distribution in the epithelium and connective tissue with or without inflammatory infiltrates were observed. Immune cells found in the biopsy tissues, including CD20+ mature B cells and CD138+ plasma cells, were associated with the Th2-type immune response. Most P. gingivalis was in direct contact with CD4+ T cells. This study revealed for the first time the colocalization of P. gingivalis with immune cells. Use of LCM combined with qRT PCR enabled quantitative analysis of bacteria in a selected area of a biopsy sample without any tissue degradation. Observation of the immune cells associated with these bacteria was also performed by immunofluorescence. PMID- 22066677 TI - Risk factors for invasive mold infections following allogeneic hematopoietic stem cell transplantation: a single center study of 190 recipients. AB - BACKGROUND: Invasive mold infection (IMI) is a major cause of infection-related mortality following allogeneic hematopoietic stem cell transplantation (allo HSCT). METHODS: We retrospectively analyzed 190 allo-HSCT recipients at Changhai Hospital between the y 2000 and 2007. The survival rate was evaluated with Kaplan Meier curves. Logistic and Cox regression models were used for multivariate analyses. RESULTS: The 1(st) y cumulative incidence rate of IMI was 12.8%, and invasive aspergillosis was the most commonly observed IMI (85%). Multivariate logistic regression analyses showed that significant predictors of IMI were corticosteroid therapy (odds ratio (OR) 1.656, 95% confidence interval (CI) 1.047 2.621, p = 0.031), positive cytomegalovirus antigenemia (OR 5.301, 95% CI 1.902 14.772, p = 0.001), and secondary neutropenia (OR 5.250, 95% CI 1.741-15.834, p = 0.003). The mortality rate of IMI at 12 weeks after diagnosis was 60%. In Cox regression models, IMI-related mortality was related to the dose of corticosteroid (2 mg/kg/day or more) administered at the time of IMI diagnosis (hazards ratio (HR) 20.841, 95% CI 2.151-201.944, p = 0.009) and neutropenia (HR 7.043, 95% CI 1.186-41.827, p = 0.032). CONCLUSIONS: These data confirm previous findings that the incidence and mortality of IMI are mostly associated with immunodeficiency caused by immunosuppressive therapy or virus infection. PMID- 22066678 TI - Effect of intracanal dentine wettability on human dental pulp cell attachment. AB - AIM: To evaluate the effect of intracanal dentine wettability on human dental pulp cell (HDPC) attachment after application of endodontic irrigants. METHODOLOGY: Twenty extracted human premolar teeth with straight canals were sectioned at the apical and coronal thirds of each root, and the remaining mid root portions were bisected longitudinally. After polishing, the specimens were divided into two groups for wettability and cell attachment measurements, respectively. The intracanal surface wettability was assessed by atomic force microscopy after a rinse of H(2) O (control), 5.25% sodium hypochlorite (NaOCl), 17% ethylenediaminetetraacetic acid (EDTA) and MTAD (n = 5). Additionally, HDPCs were seeded onto the irrigated root canal dentine and the cell attachment was evaluated by calcein-CAM and propidium iodide (PI) dying under fluorescence microscope (n = 5). Data were analysed by means of one-way anova and LSD test. RESULTS: Compared with the control group, 5.25% NaOCl, 17% EDTA and MTAD treatment significantly increased surface wettability (P < 0.001). The rank order of adhesion force was MTAD >17% EDTA >5.25% NaOCl > H(2) O. The highest average numbers of viable HDPCs were observed on the root canals irrigated with MTAD, followed by the 17% EDTA group (P < 0.001), and the lowest average numbers of viable cells were detected in the 5.25% NaOCl and H(2) O groups. CONCLUSIONS: Surface wettability was affected by the irrigants. Increasing in wettability produced higher levels of HDPC attachment to irrigated dentine. PMID- 22066680 TI - Therapeutic effect of fucoidan-stimulated endothelial colony-forming cells in peripheral ischemia. AB - BACKGROUND: Fucoidan, an antithrombotic polysaccharide, can induce endothelial colony-forming cells (ECFC) to adopt an angiogenic phenotype in vitro. OBJECTIVES: We evaluated the effect of fucoidan on vasculogenesis induced by ECFC in vivo. METHODS: We used a murine hindlimb ischemia model to probe the synergic role of fucoidan-treatment and ECFC infusion during tissue repair. RESULTS: We found that exposure of ECFC to fucoidan prior to their intravenous injection improved residual muscle blood flow and increased collateral vessel formation. Necrosis of ischemic tissue was significantly reduced on day 14, to 12.1% of the gastronecmius cross-sectional surface area compared with 40.1% in animals injected with untreated-ECFC. ECFC stimulation with fucoidan caused a rapid increase in cell adhesion to activated endothelium in flow conditions, and enhanced transendothelial extravasation. Fucoidan-stimulated ECFC were resistant to shear stresses of up to 21 dyn cm(-2). Direct binding assays showed strong interaction of fucoidan with displaceable binding sites on the ECFC membrane. Bolus intramuscular administration of fucoidan 1 day after surgery reduces rhabdomyolysis. Mice injected with fucoidan (15 mg kg(-1)) had significantly lower mean serum creatine phosphokinase (CPK) activity than control animals. This CPK reduction was correlated with muscle preservation against necrosis (P < 0.001). CONCLUSIONS: Fucoidan greatly increases ECFC-mediated angiogenesis in vivo. Its angiogenic effect would be due in part to its transportation to the ischemic site and its release after displacement by proteoglycans present in the extracellular matrix. The use of ECFC and fucoidan together, will be an efficient angiogenesis strategy to provide therapeutic neovascularization. PMID- 22066679 TI - Mitochondria as a source and target of lipid peroxidation products in healthy and diseased heart. AB - The heart is a highly oxidative organ in which cardiomyocyte turnover is virtually absent, making it particularly vulnerable to accumulation of lipid peroxidation products (LPP) formed as a result of oxidative damage. Reactive oxygen and nitrogen species are the most common electrophiles formed during lipid peroxidation and lead to the formation of both stable and unstable LPP. Of the LPP formed, highly reactive aldehydes are a well-recognized causative factor in ageing and age-associated diseases, including cardiovascular disease and diabetes. Recent studies have identified that the mitochondria are both a primary source and target of LPP, with specific emphasis on aldehydes in cardiomyocytes and how these affect the electron transport system and Ca(2+) balance. Numerous studies have found that there are functional consequences in the heart following exposure to specific aldehydes (acrolein, trans-2-hexanal, 4-hydroxynonenal and acetaldehyde). Because these LPP are known to form in heart failure, cardiac ischaemia-reperfusion injury and diabetes, they may have an underappreciated role in the pathophysiology of these disease processes. Lipid peroxidation products are involved in the transcriptional regulation of endogenous anti-oxidant systems. Recent evidence demonstrates that transient increases in LPP may be beneficial in cardioprotection by contributing to mitohormesis (i.e. induction of anti-oxidant systems) in cardiomyocytes. Thus, exploitation of the cardioprotective actions of the LPP may represent a novel therapeutic strategy for future treatment of heart disease. PMID- 22066681 TI - Theoretical calculation of the OH vibrational overtone spectra of 1,5-pentanediol and 1,6-hexanediol. AB - It is well-known that intramolecular hydrogen bonding affects the relative energetics of conformers, as well as the OH stretching peak positions, intensities, and width. In this study we simulated the Deltav(OH) = 3, 4 overtone spectra of 1,5-pentanediol (PeD) and 1,6-hexanediol (HD) using the peak positions, intensities, and width calculated from the B3LYP/6-31+G(d,p) method. Furthermore, room temperature free energy calculations were performed using B3LYP/6-31+G(d,p) MP2/6-31+G(d,p), and MP2/6-311++G(3df,3pd) to obtain the relative population of the conformers. From the calculation of 109 and 381 distinct conformers for PeD and HD, respectively, we find that for these long chain diols the intramolecular hydrogen bonded conformers are not the most dominant conformation at room temperature. This is in stark contrast with shorter chain diols such as ethylene glycol for which the hydrogen bonded conformer dominates the population at room temperature. On the other hand, we found that the correlation between the hydrogen bonded OH red shift versus the homogeneous width, Gamma = 0.0155(Deltaomega)(1.36), which was derived for shorter chain diols, is valid even for these longer chain diols. We also showed that the intramolecular hydrogen bonded OH initially decays through the CCOH torsion and COH bending mode no matter how long the alkanediol chain length is for 1,n alkanediols for n up to 6. PMID- 22066682 TI - Transthoracic echocardiographic features of cardiac pheochromocytoma: a single institution experience. AB - BACKGROUND: Cardiac pheochromocytoma is extremely rare. Previous papers usually are reports of a single case. Transthoracic echocardiography (TTE) offers a useful option, but the features of cardiac pheochromocytoma on TTE have not been favorably reported. In this study, the findings of cardiac pheochromocytoma on TTE in nine cases were presented. METHODS: TTE images (especially two-dimensional ultrasound) of nine patients with cardiac pheochromocytomas were analyzed retrospectively and compared with the findings from surgery. RESULTS: Among the nine patients with cardiac pheochromocytomas identified in Peking Union Medical College Hospital (PUMCH) clinical and echocardiographic database, TTE identified one cardiac tumor in seven cases (77.8%), two cardiac tumors in one case (11.1%), and a false-negative result in another (11.1%). Cardiac pheochromocytomas were usually located on the base of the heart, near the origin of great arteries. The tumors were usually round or ovoid, ranging from 1.4 cm to 7.7 cm in diameter, with homogeneous and moderate echoes and low activity. They could press or invade surrounding cardiac structures and influence hemodynamics. In this study the majority of cardiac pheochromocytoma seemed marginated and appeared to be encapsulated on TTE. Apical four-chamber view and parasternal short-axis view of the aortic valve were most effective in identifying cardiac pheochromocytomas. The findings on TTE were similar to those from surgical procedures. CONCLUSION: Cardiac pheochromocytomas presented characteristic TTE appearances in aspect of location, size, texture, and shape of tumors. Understanding of these characteristics on TTE can help correctly recognize this extremely rare disease. PMID- 22066683 TI - Characterization of low energy charge transfer transitions in (terpyridine)(bipyridine)ruthenium(II) complexes and their cyanide-bridged bi- and tri-metallic analogues. AB - The lowest energy metal-to-ligand charge transfer (MLCT) absorption bands found in ambient solutions of a series of [Ru(tpy)(bpy)X](m+) complexes (tpy = 2,2':3',2''-terpyridine; bpy = 2,2'-bipyridine; and X = a monodentate ancillary ligand) feature one or two partly resolved weak absorptions (bands I and/or II) on the low energy side of their absorption envelopes. Similar features are found for the related cyanide-bridged bi- and trimetallic complexes. However, the weak absorption band I of [(bpy)(2)Ru{CNRu(tpy)(bpy)}(2)](4+) is missing in its [(bpy)(2)Ru{NCRu(tpy)(bpy)}(2)](4+) linkage isomer demonstrating that this feature arises from a Ru(II)/tpy MLCT absorption. The energies of the MLCT band I components of the [Ru(tpy)(bpy)X](m+) complexes are proportional to the differences between the potentials for the first oxidation and the first reduction waves of the complexes. Time-dependent density functional theory (TD DFT) computational modeling indicates that these band I components correspond to the highest occupied molecular orbital (HOMO) to lowest unoccupied molecular orbital (LUMO) transition, with the HOMO being largely ruthenium-centered and the LUMO largely tpy-centered. The most intense contribution to a lowest energy MLCT absorption envelope (band III) of these complexes corresponds to the convolution of several orbitally different components, and its absorption maximum has an energy that is about 5000 cm(-1) higher than that of band I. The multimetallic complexes that contain Ru(II) centers linked by cyanide have mixed valence excited states in which more than 10% of electronic density is delocalized between the nearest neighbor ruthenium centers, and the corresponding stabilization energy contributions in the excited states are indistinguishable from those of the corresponding ground states. Single crystal X-ray structures and computational modeling indicate that the Ru-(C=N)-Ru linkage is quite flexible and that there is not an appreciable variation in electronic structure or energy among the conformational isomers. PMID- 22066684 TI - A new assay for endonuclease/methyltransferase activities based on graphene oxide. AB - A new endonuclease/methyltransferase activity assay method based on graphene oxide (GO) is developed. Substrate DNA is designed to possess a double-stranded part to serve as a nuclease substrate and a single-stranded part for anchoring the DNA to the GO surface via strong noncovalent binding. Nuclease-mediated DNA hydrolysis induces the recovery of fluorescence intensity of the dye attached to the end of the double-stranded DNA region. This GO-based method allows real-time measurement and quantitative assay for endonuclease/methyltransferase activities in short time. PMID- 22066685 TI - Motion interactive video games in home training for children with cerebral palsy: parents' perceptions. AB - PURPOSE: To explore parents' perceptions of using low-cost motion interactive video games as home training for their children with mild/moderate cerebral palsy. METHOD: Semi-structured interviews were carried out with parents from 15 families after participation in an intervention where motion interactive games were used daily in home training for their child. A qualitative content analysis approach was applied. RESULTS: The parents' perception of the training was very positive. They expressed the view that motion interactive video games may promote positive experiences of physical training in rehabilitation, where the social aspects of gaming were especially valued. Further, the parents experienced less need to take on coaching while gaming stimulated independent training. However, there was a desire for more controlled and individualized games to better challenge the specific rehabilitative need of each child. CONCLUSIONS: Low-cost motion interactive games may provide increased motivation and social interaction to home training and promote independent training with reduced coaching efforts for the parents. In future designs of interactive games for rehabilitation purposes, it is important to preserve the motivational and social features of games while optimizing the individualized physical exercise. PMID- 22066687 TI - The influence of pre-admission hypoglycaemic therapy on cardiac morbidity and mortality in type 2 diabetic patients undergoing major non-cardiac surgery: a prospective observational study. AB - It remains unclear whether type 2 diabetics treated with either insulin or oral hypoglycaemic agents have the same incidence of cardiac morbidity and mortality after major non-cardiac surgery. We prospectively studied 360 type 2 diabetic patients undergoing major non-cardiac surgery of which 105 were treated with insulin only, 171 were treated with oral hypoglycaemics only and 84 were treated with a combination of insulin and oral hypoglycaemics. All-cause mortality after 30 days and after 12 months was highest in the insulin (10% and 26%) and lowest in the oral hypoglycaemics group (2% and 13%; p = 0.02 and 0.007, respectively). Insulin treatment was independently associated with increased mortality after 30 days (hazard ratio 3.93; 95% CI 1.22-12.64; p = 0.022) and 12 months (hazard ratio 2.03; 95% CI 1.16-3.58; p = 0.014) after multivariate adjustment for age, sex and the revised cardiac risk index (insulin treatment excluded). The increased mortality in insulin-treated diabetic patients may be due to a more progressive disease state in these patients rather than the treatment modality itself. PMID- 22066688 TI - Asymmetric toggling of a natural photoswitch: ultrafast spectroscopy of Anabaena sensory rhodopsin. AB - Photochemistry in retinal proteins (RPs) is determined both by the properties of the retinal chromophore and by its interactions with the surrounding protein. The initial retinal configuration, and the isomerization coordinates active in any specific protein, must be important factors influencing the course of photochemistry. This is illustrated by the vast differences between the photoisomerization dynamics in visual pigments which start 11-cis and end all trans, and those observed in microbial ion pumps and sensory rhodopsins which start all-trans and end in a 13-cis configuration. However, isolating these factors is difficult since most RPs accommodate only one active stable ground state configuration. Anabaena sensory rhodopsin, allegedly functioning in cyanobacteria as a wavelength sensor, exists in two stable photoswitchable forms, containing all-trans and 13-cis retinal isomers, at a wavelength-dependent ratio. Using femtosecond spectroscopy, and aided by extraction of coherent vibrational signatures, we show that cis-to-trans photoisomerization, as in visual pigments, is ballistic and over in a fraction of a picosecond, while the reverse is nearly 10 times slower and kinetically reminiscent of other microbial rhodopsins. This provides a new test case for appreciating medium effects on primary events in RPs. PMID- 22066689 TI - Heparan sulfate enhances the self-renewal and therapeutic potential of mesenchymal stem cells from human adult bone marrow. AB - Insufficient cell number hampers therapies utilizing adult human mesenchymal stem cells (hMSCs) and current ex vivo expansion strategies lead to a loss of multipotentiality. Here we show that supplementation with an embryonic form of heparan sulfate (HS-2) can both increase the initial recovery of hMSCs from bone marrow aspirates and increase their ex vivo expansion by up to 13-fold. HS-2 acts to amplify a subpopulation of hMSCs harboring longer telomeres and increased expression of the MSC surface marker stromal precursor antigen-1. Gene expression profiling revealed that hMSCs cultured in HS-2 possess a distinct signature that reflects their enhanced multipotentiality and improved bone-forming ability when transplanted into critical-sized bone defects. Thus, HS-2 offers a novel means for decreasing the expansion time necessary for obtaining therapeutic numbers of multipotent hMSCs without the addition of exogenous growth factors that compromise stem cell fate. PMID- 22066690 TI - UV-responsive polymeric superamphiphile based on a complex of malachite green derivative and a double hydrophilic block copolymer. AB - We have prepared a UV-responsive polymeric superamphiphile, formed by a malachite green derivative and the double hydrophilic block copolymer methoxy-poly(ethylene glycol)(114)-block-poly(l-lysine hydrochloride)(200) (PEG-b-PLKC) on the basis of electrostatic interactions. The malachite green derivative undergoes photo ionization upon UV irradiation, which makes it more hydrophilic, resulting in changes in the self-assembly behavior of the polymeric superamphiphile. For this reason, the polymeric superamphiphile originally self-assembles to form sheetlike aggregates, which disassemble after UV irradiation because of the increased solubility of the malachite green derivative. By use of Nile red as a probe, the polarity of the polymeric superamphiphile solution is confirmed to be increased after UV irradiation by fluorescence spectra, which also explains the disassembly of the polymeric superamphiphile. PMID- 22066691 TI - Differences in treatment and survival among African-American and Caucasian women with early stage operable breast cancer. AB - OBJECTIVE: To examine racial disparities associated with breast cancer treatment and survival in elderly patients with early stage operable breast cancer. METHODS: We studied 23,110 women with node-positive and 31,572 women with node negative tumor who were aged >=65 with stages I, II, or IIIA breast cancer in 1991-2002 using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. Logistic regression analyses were performed to assess the odds of receiving adjuvant chemotherapy and radiation after breast conserving surgery (BCS) for blacks compared to whites. Cox proportional hazard regression models were used to determine the risk of mortality in blacks compared to whites, stratified by types of treatment. RESULTS: Black women with node-positive and node-negative tumors were 25% (odds ratio = 0.75, 95% CI = 0.65-0.87) and 17% (0.83, 0.70-0.99) less likely to receive chemotherapy than white women, after adjusting for patient and tumor characteristics. This relation was not attenuated and remained statistically significant even after adjustment for socioeconomic status. In women with node-negative tumor who did not receive chemotherapy, black women were significantly more likely to die than white women (hazard ratio (HR) = 1.14, 95% CI = 1.04-1.24) after adjusting for patient and tumor characteristics, and comorbidity; and (1.11, 1.01-1.22) after additionally adjusting for socioeconomic status. CONCLUSIONS: There were racial disparities between black and white women in receiving adjuvant chemotherapy and radiotherapy following BCS. Higher risk of mortality in black compared to white women was found only in those receiving no chemotherapy. Future studies should explore the root causes of racial disparities beyond treatment factors. PMID- 22066692 TI - Potential beneficial effects of low molecular weight heparin on cognitive impairment in elderly patients on haemodialysis. AB - Vascular cognitive impairment or mixed vascular cognitive impairment and Alzheimer's disease (AD) appear to be much more common in elderly patients than AD alone. Furthermore, vascular dementia (VaD) and AD are more prevalent in elderly patients receiving haemodialysis (HD), leading to a loss of independence and a poor quality of life. Hypotensive episodes in patients receiving HD contribute to vascular changes in the brain, with consequent progression of VaD and AD. The use of the lowest individually optimized bolus dose of low molecular weight heparin (LMWH) during HD, with fewer hypotensive episodes during and between HD procedures, may exert a sparing effect on changes in microvascular circulation and decrease the incidence of VaD and AD. We believe that long-term use of LMWH, with its direct effect on amyloid beta protein (Abeta) in the blood and on Abeta accumulation in the brain and indirect effects on prevention of complement activation, may delay the progression of cognitive impairment in patients receiving HD. There is a need for a robustly designed, prospective trial to evaluate the effects of long-term treatment with LMWH on mild cognitive impairment, VaD and AD in elderly patients receiving maintenance HD. PMID- 22066694 TI - Vasodilatory activity and antihypertensive profile mediated by inhibition of phosphodiesterase type 1 induced by a novel sulfonamide compound. AB - LASSBio-985 is a sulfonamide compound designed as a simplified structure of a nonselective phosphodiesterase type 4 (PDE-4) inhibitor that promotes vasodilatory activity in vitro. PDE are enzymes responsible for the hydrolysis of cyclic adenosine 3',5'- monophosphate and cyclic guanosine 3',5'-monophosphate. Five different isozymes of PDE are found in vascular smooth muscle (PDE1-PDE5). Aortic rings, with or without endothelium, from male normotensive and spontaneously hypertensive rats (SHR) were prepared for isometric tension recording. Blood pressure was measured in Wistar Kyoto (WKY) rats and SHR during intravenous infusion of LASSBio-985 (10 mg/kg/min) during 15 min. LASSBio-985 induced a concentration-dependent vasodilation in aortic rings from normotensive and SHR, which was almost completely inhibited in endothelium-denuded vessels. Vasodilatory activity was also reduced in endothelium-intact aortic rings that had been pretreated with N(omega)-nitro-L-arginine methyl ester hydrochloride (L NAME), a nitric oxide synthase inhibitor and 1H-[1,2,4]oxadiazolod[4,3 a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. LASSBio-985-induced vasodilation was also inhibited by sildenafil (100 MUm) and SQ 22536, a PDE5 inhibitor and adenylate cyclase inhibitor, respectively. To evaluate the involvement of some endothelial receptors, atropine, diphenhydramine, HOE 140, naloxone, propranolol, indomethacin, and wortmannin were tested, but none inhibited the effects of LASSBio-985. The residual effect observed on endothelium denuded aortic rings was abolished by nicardipine, a voltage-sensitive-Ca(2+) channel blocker. Intravenous infusion of LASSBio-985 (10 mg/kg/min) significantly reduced systolic and diastolic pressures in both WKY and SHR. LASSBio-985 is a compound with vasodilatory activity, which could be consequent to PDE1 inhibition and voltage-sensitive-Ca(2+)-channel blockade. PMID- 22066695 TI - Soil characteristics more strongly influence soil bacterial communities than land-use type. AB - To gain insight into the factors driving the structure of bacterial communities in soil, we applied real-time PCR, PCR-denaturing gradient gel electrophoreses, and phylogenetic microarray approaches targeting the 16S rRNA gene across a range of different land usages in the Netherlands. We observed that the main differences in the bacterial communities were not related to land-use type, but rather to soil factors. An exception was the bacterial community of pine forest soils (PFS), which was clearly different from all other sites. PFS had lowest bacterial abundance, lowest numbers of operational taxonomic units (OTUs), lowest soil pH, and highest C : N ratios. C : N ratio strongly influenced bacterial community structure and was the main factor separating PFS from other fields. For the sites other than PFS, phosphate was the most important factor explaining the differences in bacterial communities across fields. Firmicutes were the most dominant group in almost all fields, except in PFS and deciduous forest soils (DFS). In PFS, Alphaproteobacteria was most represented, while in DFS, Firmicutes and Gammaproteobacteria were both highly represented. Interestingly, Bacillii and Clostridium OTUs correlated with pH and phosphate, which might explain their high abundance across many of the Dutch soils. Numerous bacterial groups were highly correlated with specific soil factors, suggesting that they might be useful as indicators of soil status. PMID- 22066697 TI - European veterinary dissertations. PMID- 22066698 TI - Trend analysis of cancer incidence in Japan using data from selected population based cancer registries. AB - Population-based cancer registries are operated by over 80% of prefectures in Japan. However, only a limited proportion of the registries can provide long-term incidence data. Here, we aimed to establish a method for monitoring cancer incidence trends in Japan using data from selected prefectures. Based on the availability of long-term (>= 20 years) high-quality data, we collected incidence data from five prefectures (Miyagi, Yamagata, Fukui, Osaka, and Nagasaki), which included an annual average of 54,539 primary cancer cases diagnosed between 1985 and 2004. Cancer mortality data for 1995-2004 were obtained from the vital statistics. Representativeness and homogeneity of the trends were examined by funnel plot analysis of log-linear regression coefficients calculated for the most recent 10 years of data (1995-2004) of age-standardized rates (ASR). The ASR of incidence for five prefectures in total (5-pref total) showed a significant decrease, with an annual percent change (APC) of -1.0 (95% confidence interval [CI] -1.4: -0.6) for males and -0.4 (95% CI -0.8: -0.1) for females. Excluding data from Osaka (4-pref total) reversed the decreasing trend; the corresponding APC was +0.4 (95% CI -0.2: +1.0) for males and +0.7 (95% CI +0.5: +0.9) for females. The APCs for the ASR of mortality for the 4-pref total (males, -1.5; females, -1.3) were more representative of nationwide data (males, -1.4 [95% CI 1.7: -1.2]; females, -1.1 [95% CI -1.4: -0.9]) than those for the 5-pref total (males, -1.7; females, -1.4). We conclude that using data from Miyagi, Yamagata, Fukui, and Nagasaki prefectures, with continuous monitoring of the representativeness of the data, is a provisionally relevant way to evaluate cancer incidence trends in Japan. PMID- 22066699 TI - Altered phosphate metabolism in HIV-1-infected patients with metabolic syndrome. AB - BACKGROUND: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that has become a serious problem for HIV-1-infected patients. It has been proposed that disturbance of phosphate metabolism may represent a key feature of MS. Thus, we undertook the present study to investigate the relationship between phosphate levels and the presence of the characteristics of MS. METHODS: One hundred and twenty-one HIV-1-infected patients were consecutively enrolled in a prospective, cross-sectional, single-centre study. Kidney tubular function was examined using tubular resorption of phosphate and normalized renal threshold phosphate concentration. RESULTS: Univariate analysis showed that serum phosphate levels correlated negatively with systolic and diastolic blood pressure, glucose values, waist circumference, insulin, and triglycerides. Moreover, there was a positive relationship between phosphate and high-density lipoprotein (HDL) cholesterol. Multivariate analysis showed that insulin levels were correlated with serum phosphate concentration (r = - 0.24, p = 0.01). CONCLUSIONS: Our data show that HIV-1-infected patients with MS have lower phosphate levels. PMID- 22066696 TI - Isolation and gene flow: inferring the speciation history of European house mice. AB - Inferring the history of isolation and gene flow during species differentiation can inform us on the processes underlying their formation. Following their recent expansion in Europe, two subspecies of the house mouse (Mus musculus domesticus and Mus musculus musculus) have formed a hybrid zone maintained by hybrid incompatibilities and possibly behavioural reinforcement, offering a good model of incipient speciation. We reconstruct the history of their divergence using an approximate Bayesian computation framework and sequence variation at 57 autosomal loci. We find support for a long isolation period preceding the advent of gene flow around 200,000 generations ago, much before the formation of the European hybrid zone a few thousand years ago. The duration of the allopatric episode appears long enough (74% of divergence time) to explain the accumulation of many post-zygotic incompatibilities expressed in the present hybrid zone. The ancient contact inferred could have played a role in mating behaviour divergence and laid the ground for further reinforcement. We suggest that both subspecies originally colonized the Middle East from the northern Indian subcontinent, domesticus settling on the shores of the Persian Gulf and musculus on those of the Caspian Sea. Range expansions during interglacials would have induced secondary contacts, presumably in Iran, where they must have also interacted with Mus musculus castaneus. Future studies should incorporate this possibility, and we point to Iran and its surroundings as a hot spot for house mouse diversity and speciation studies. PMID- 22066700 TI - Modulation of Pseudomonas aeruginosa lipopolysaccharide-induced lung inflammation by chronic iron overload in rat. AB - Iron constitutes a critical nutrient source for bacterial growth, so iron overload is a risk factor for bacterial infections. This study aimed at investigating the role of iron overload in modulating bacterial endotoxin-induced lung inflammation. Weaning male Wistar rats were intraperitoneally injected with saline or iron sucrose [15 mg kg(-1) body weight (bw), 3 times per week, 4 weeks]. They were then intratracheally injected with Pseudomonas aeruginosa lipopolysaccharide (LPS) (5 MUg kg(-1) bw) or saline. Inflammatory indices were evaluated 4 or 18 h post-LPS/saline injection. At 4 h, LPS-treated groups revealed significant increases in the majority of inflammatory parameters (LPS binding protein (LBP), immune cell recruitment, inflammatory cytokine synthesis, myeloperoxidase activity, and alteration of alveolar-capillary permeability), as compared with control groups. At 18 h, these parameters reduced strongly with the exception for LBP content and interleukin (IL)-10. In parallel, iron acted as a modulator of immune cell recruitment; LBP, tumor necrosis factor-alpha, cytokine induced neutrophil chemoattractant 3, and IL-10 synthesis; and alveolar-capillary permeability. Therefore, P. aeruginosa LPS may only act as an acute lung inflammatory molecule, and iron overload may modulate lung inflammation by enhancing different inflammatory parameters. Thus, therapy for iron overload may be a novel and efficacious approach for the prevention and treatment of bacterial lung inflammations. PMID- 22066701 TI - Differential effector responses by circulating/blood and tissue/peritoneal neutrophils following burn combined with Enterococcus faecalis infection. AB - Recently we found that superimposition of Enterococcus faecalis infection on burn injury caused an eruption of host mortality not seen with either individual challenge. We hypothesized that the Enterococcus bacteria, and/or factors related to these organisms, aggravate burn-induced modulations in host defense by neutrophils. Our study focuses on alterations in neutrophils' oxidative, proteolytic, and adhesive functions and transendothelial migration of neutrophils in burn rats inoculated with E. faecalis. Rats were subjected to burn (30% total body surface area) and then intra-abdominally inoculated with E. faecalis (10(4)CFU kg(-1) b.w). Polymorphonuclear neutrophils (PMNs) were harvested from circulating/blood and tissue/peritoneal cavity at day-2 post injury. Extracellular release of O(-)(2) anion production was determined by luminometry, and intracellular production of reactive oxygen species was measured by digital imaging technique. Fluoroscan analysis and confocal microscopy determined intracellular elastase production. The expression of adhesion molecule CD11b/CD18 was performed by flow cytometry. Calcein AM-labeled PMNs were co-cultured with TNF-alpha-stimulated rat lung microvascular endothelial cells, and their ability to adhere was assessed by fluorometry and digital imaging and finally, chemotaxis was measured by neutrophil transmigration assays. The results showed differential effector responses by circulatory and/or tissue PMNs. Tissue/peritoneal PMNs produced more O(-)(2), less intracellular elastase, and increased expression of CD11b/CD18 accompanied with increased adhesivity of MIP-2-stimulated PMNs to endothelial cells as compared to circulatory/blood PMNs. This differential effect was more pronounced following burn plus E. faecalis infection, indicating that the combined injury changed neutrophil functions. PMID- 22066702 TI - Diversity and distribution of diazotrophic communities in the South China Sea deep basin with mesoscale cyclonic eddy perturbations. AB - The South China Sea (SCS) is an oligotrophic subtropical marginal ocean with a deep basin and a permanently stratified central gyre. Upwelling and nitrogen fixation provide new nitrogen for primary production in the SCS. This study was aimed at an investigation of phylogenetic diversity and quantification of the diazotroph community in the SCS deep basin, which is characterized by frequent mesoscale eddies. The diazotroph community had a relatively low diversity but a distinct spatial heterogeneity of diversity in the SCS deep basin. The potential for nitrogen fixation consistently occurred during cyclonic eddies, although upwelling of nutrient-replete deep water might have alleviated nitrogen limitation in the SCS. However, diazotrophic proteobacteria were dominant, but neither Trichodesmium nor heterocystous cyanobacterial diatom symbionts. Quantitative PCR analysis using probe-primer sets developed in this study revealed that the nif H gene of the two dominant alpha- and gammaproteobacterial groups was at the highest abundance (up to 10(4) to 10(5) copies L(-1) ). Trichodesmium thiebautii was detected with an average density of 10(2) trichomes L(-1) in the euphotic waters, while Richelia intracellularis was observed sporadically under the microscope. The unicellular cyanobacterial groups A and B were not detected in our libraries. Our results suggested that diazotrophic proteobacteria were significant components potentially contributing to nitrogen fixation in this oligotrophic marginal ocean ecosystem. PMID- 22066703 TI - Substance use among populations displaced by conflict: a literature review. AB - This paper reviews the literature on substance use among populations displaced by conflict. Of the 17 publications presenting primary data retained for review, all consider populations in or recovering from protracted conflict, the majority (10) in non-camp settings. Most studies (10) offer prevalence estimates, suggesting that substance use (such as of alcohol, opiates, or minor tranquilizers) is common in some displaced settings. Five describe harmful consequences of substance use among displaced populations (such as HIV transmission, tuberculosis treatment failure, gender-based violence, and economic problems). Three studies suggest risk factors for substance use problems (such as gender, trauma-related conditions, pre-displacement substance use, and socio-economic factors); two examine qualitatively the gendered nature of alcohol-related harm and its links with gender-based violence. One study examines an intervention. The evidence base is weak. Findings are used to develop a conceptual framework emphasizing the risk environment to inform further research, to encourage debate among researchers and practitioners, and to enable the development of interventions. PMID- 22066704 TI - Universal pharmacological thromboprophylaxis for total knee arthroplasty may not be necessary in low-risk populations: a nationwide study in Taiwan. AB - BACKGROUND: Thromboprophylaxis should be universally administered in major orthopedic surgery. However, epidemiology of venous thromboembolism (VTE) following major knee surgery in Asia is scarce. OBJECTIVE: To describe the use of thromboprophylaxis and calculate the incidence and risk factors of symptomatic VTE following major knee surgery in Taiwan. METHODS: We used Taiwan's National Health Insurance Research Database to retrospectively identify patients (>=45 years) who underwent major knee surgery from 1998 to 2007 and collected the medical records within 3 months after the discharge. Logistic regression analysis was used to determine the risk factors of symptomatic VTE after the surgery. RESULTS: We identified 113 844 patients (mean age, 69.0 +/- 7.7 years; female, 75.2%) receiving major knee arthroplasties. The mean length of stay was 9.1 +/- 3.3 days. The overall pharmacological thromboprophylaxis rate was 2.2%. The 3 month cumulative incidence of procedure-related symptomatic VTE was 0.46% (95% CI, 0.42-0.50%). The median time to the first post-operation VTE was 7 days, with 85.4% occurring within 2 weeks after the discharge.Logistic regression analysis showed that previous VTE, malignancy, heart failure and neurologic disorder with extremity paralysis or pararesis were independent risk factors (P < 0.05) for symptomatic VTE following major knee arthroplasties. CONCLUSIONS: The thromboprophylaxis rate is low, which may be due to the very low incidence of symptomatic VTE after the surgery in Taiwan. Most symptomatic VTE occurred within 2 weeks after the surgery. Universal thromboprophylaxis for knee arthroplasties may not be necessary in Taiwan, but it should be considered in some high-risk populations. PMID- 22066705 TI - Photoinduced electron transfer (PET) based Zn2+ fluorescent probe: transformation of turn-on sensors into ratiometric ones with dual emission in acetonitrile. AB - Ratiometric sensors for the detection of metal ions have gained increasing attention due to its self-calibration tendency for the environmental effects. In this context, we have synthesized and characterized a dual emitting ratiometric Zn(2+) probe (1) having acridinedione as a fluorophore and N,N-bis(2 pyridylmethyl)amine (BPA) as a receptor unit. Existence of two different conformation of the molecule with photoinduced electron transfer (PET) from amine moiety to the acridinedione fluorophore leads to dual emission, namely locally excited (425 nm) and anomalous charge transfer emission (560 nm) in aprotic solvents. In the presence of one equivalent of Zn(2+), a 15-fold fluorescence enhancement in the locally excited state together with the quenching of charge transfer emission is observed. The intensity changes at the two emission peaks allow a ratiometric detection of Zn(2+) under PET signaling mechanism. The utilization of PET process for the ratiometric fluorescence change will further signify the importance of PET mechanism in sensing action. Addition of Zn(2+) to 1 in acetonitrile/water mixtures shows a single emission peak with fluorescence enhancement. PMID- 22066706 TI - A more informative approach for characterization of polymer monolithic phases: small angle neutron scattering/ultrasmall angle neutron scattering. AB - Neutron scattering techniques have been used frequently to characterize geological specimens and to determine the structures of glasses and of polymers as solutions, suspensions, or melts. Little work has been reported on their application in determining polymers' structural properties relevant to separations. Here, we present a comparison of characterization results from nitrogen porosimetry and from combined small angle neutron scattering (SANS) and ultrasmall angle neutron scattering (USANS) experiments. We show that SANS is extremely sensitive to the pore characteristics. Both approaches can provide information about porosity and pore characteristics, but the neutron scattering techniques provide additional information in the form of the surface characteristics of the pores and their length scales. Fits of the scattering data show that cylindrical pores are present with diameters down to 0.6 MUm and that, for length scales down to approxmately 20 A, the material shows self-similar (fractal) slopes of -3.4 to -3.6. Comparison of these characteristics with other examples from the scattering literature indicate that further investigation of their meaning for chromatographic media is required. PMID- 22066707 TI - Realizing visible-light-induced self-cleaning property of cotton through coating N-TiO2 film and loading AgI particles. AB - The visible-light-induced self-cleaning property of cotton has been realized by coating N-TiO(2) film and loading AgI particles simultaneously. The physical properties were characterized by means of XRD, SEM, TEM, XPS, and DRS techniques. The visible light photocatalytic activities of the materials were evaluated using the degradation of methyl orange. In comparison with TiO(2)-cotton, the dramatic enhancement in the visible light photocatalytic performance of the AgI-N-TiO(2) cotton could be attributed to the synergistic effect of AgI and N-TiO(2), including generation of visible light photocatalytic activity and the effective electron-hole separations at the interfaces of the two semiconductors. The photocatalytic activity of the AgI-N-TiO(2)-cotton was fully maintained upon several numbers of photodegradation cycles. In addition, according to the XRD patterns of the AgI-N-TiO(2)-cotton before and after reaction, AgI was stable in the composites under visible light irradiation. Moreover, a possible mechanism for the excellent and stable photocatalytic activity of AgI-N-TiO(2)-cotton under visible light irradiation was also proposed. PMID- 22066708 TI - Emotional well-being and adjustment to vision loss in later life: a meta synthesis of qualitative studies. AB - PURPOSE: To review perceived emotional well-being in older people with visual impairment and perceived factors that inhibit/facilitate psychosocial adjustment to vision loss. METHOD: The databases of MEDLINE, EMBASE, PsycINFO and CINAHL were searched for studies published from January 1980 to December 2010, which recruited older people with irreversible vision loss, and used qualitative methods for both data collection and analysis. Results sections of the papers were synthesised using a thematic-style analysis to identify the emergent and dominant themes. RESULTS: Seventeen qualitative papers were included in the review, and five main themes emerged from the synthesis: 1) the trauma of an ophthalmic diagnosis, 2) impact of vision loss on daily life, 3) negative impact of visual impairment on psychosocial well-being, 4) factors that inhibit social well-being, and 5) factors that facilitate psychological well-being. We found the response shift model useful for explaining our synthesis. CONCLUSIONS: Acquired visual impairment can have a significant impact on older people's well-being and make psychosocial adjustment to the condition a major challenge. Acceptance of the condition and a positive attitude facilitate successful psychosocial adjustment to vision loss as well as social support from family, friends and peers who have successfully adjusted to the condition. PMID- 22066709 TI - Cutaneous involvement with B-lineage acute lymphoblastic leukemia. PMID- 22066710 TI - Breast implant-associated anaplastic large cell lymphoma: a newly recognized entity that needs further refinement of its definition. PMID- 22066711 TI - Non-relapse mortality in pediatric acute lymphoblastic leukemia: a systematic review and meta-analysis. AB - The primary objective of the study was to describe non-relapse mortality (NRM) and the proportion of first events that are deaths in children with acute lymphoblastic leukemia (ALL). Secondary objectives were to identify groups at higher risk and to determine whether proportions have changed over time. We performed a systematic review of randomized pediatric ALL studies. From 1337 articles, 59 were included, comprising a total of 49 071 patients. The induction death rate was 1.38%, remission death rate was 1.94% and total NRM was 3.60%. Deaths were responsible for 53.84% of first events during induction and 13.03% in total. Standard risk patients had significantly lower NRM during remission. The year of study was not associated with NRM. The results of the study show that the rate of NRM in children with ALL is 3.60% and those with high risk ALL have significantly higher NRM during remission, but NRM has not changed over time. Future research should focus on the exploration of patient-related risk factors for NRM. PMID- 22066712 TI - A novel CCAAT/enhancer binding protein alpha germline variant in a case of acute myeloid leukemia. PMID- 22066713 TI - LIM domain only 2 protein expression, LMO2 germline genetic variation, and overall survival in diffuse large B-cell lymphoma in the pre-rituximab era. AB - Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] = 0.55; 95% confidence interval [CI] 0.31-0.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p = 0.02). Compared to a model with clinical factors only (c-statistic = 0.676), adding the four SNPs (c-statistic = 0.751) or LMO2 IHC (c-statistic = 0.691) increased the predictive ability of the model, while inclusion of all three factors (c statistic = 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status. PMID- 22066714 TI - The fast and the slow: folding and trapping of lambda6-85. AB - Molecular dynamics simulations combining many microsecond trajectories have recently predicted that a very fast folding protein like lambda repressor fragment lambda(6-85) D14A could have a slow millisecond kinetic phase. We investigated this possibility by detecting temperature-jump relaxation to 5 ms. While lambda(6-85) D14A has no significant slow phase, two even more stable mutants do. A slow phase of lambda(6-85) D14A does appear in mild denaturant. The experimental data and computational modeling together suggest the following hypothesis: lambda(6-85) takes only microseconds to reach its native state from an extensively unfolded state, while the latter takes milliseconds to reach compact beta-rich traps. lambda(6-85) is not only thermodynamically but also kinetically protected from reaching such "intramolecular amyloids" while folding. PMID- 22066715 TI - Immediate recall influences the effects of pre-encoding stress on emotional episodic long-term memory consolidation in healthy young men. AB - The stress-associated activation of the hypothalamus-pituitary-adrenal axis influences memory. Several studies have supported the notion that post-learning stress enhances memory consolidation, while pre-retrieval stress impairs retrieval. Findings regarding the effects of pre-encoding stress, in contrast, have been rather inconsistent. In the current two studies, the impact of an immediate retrieval task on these effects was explored. In the first study, 24 healthy young male participants were exposed to a psychosocial laboratory stressor (Trier Social Stress Test) or a control condition before viewing positive, negative, and neutral photographs, which were accompanied by a brief narrative. Immediate as well as delayed (24 h later) free recall was assessed. Stress was expected to enhance emotional long-term memory without affecting immediate recall performance. Stress caused a significant increase in salivary cortisol concentrations but had no significant effects on immediate or delayed retrieval performance, even though a trend toward poorer memory of the stress group was apparent. Based on these findings, the second experiment tested the hypothesis that the beneficial effects of stress on emotional long-term memory performance might be abolished by an immediate recall test. In the second study (n = 32), the same design was used, except for the omission of the immediate retrieval test. This time stressed participants recalled significantly more negative photographs compared to the control group. The present study indicates that an immediate retrieval attempt of material studied after stress exposure can prevent or even reverse the beneficial effects of pre-encoding stress on emotional long-term memory consolidation. PMID- 22066716 TI - Calibration and prediction of amino acids in stevia leaf powder using near infrared reflectance spectroscopy. AB - The use of stevia as animal feed additive has been researched over the years, but how to rapidly predict its amino acid contents has not been studied yet by using near-infrared reflectance spectroscopy. In the present study, 301 samples of stevia leaf powder were defined as the calibration set from which calibration models were optimized, and the performance of prediction was evaluated. Compared with other mathematical treatments, the models developed with the "1, 12, 12, 1" treatment, combined with modified partial least-squares regression and standard normal variance with de-trending, had a significant potential in predicting amino acid contents, such as threonine, serine, etc. Six spectral regions were found to possess large spectrum variation and show high contribution to calibration models. From the present study, the calibration models of amino acids in stevia were successfully developed and could be applied to quality control in feed processing, breeding selection and mutant screening. PMID- 22066717 TI - Management of pediatric eosinophilic esophagitis: an update. AB - Eosinophilic esophagitis is an important chronic esophageal disorder with gastroesophageal reflux disease (GERD)-like symptoms, prominent esophageal mucosal eosinophilia, strongly associated with allergic disorders and unresponsive to anti-GERD therapy. Treatment of eosinophilic esophagitis has been successful with the use of dietary restrictions and topical corticosteroids. A subset of patients benefits from concurrent anti-GERD therapy; those with demonstrable esophageal strictures report variable duration symptom relief after esophageal dilation. At the current time, anti-interleukin-5 monoclonal antibody agents are being investigated in multicenter trials, and it is hoped that future therapy may be targeted against mediators of esophageal remodeling and fibrosis in eosinophilic esophagitis. PMID- 22066718 TI - Identification and characterization of C106R, a novel mutation in the DNA-binding domain of GCMB, in a family with autosomal-dominant hypoparathyroidism. AB - OVERVIEW: Glial cells missing B (GCMB) is a transcription factor that is expressed in the parathyroid hormone (PTH)-secreting cells of the parathyroid glands. Several mutations in GCMB have been reported to cause hypoparathyroidism (HP). We identified a family with two individuals in two generations (mother and son), who are affected by autosomal-dominant hypoparathyroidism (AD-HP). A novel heterozygous mutation in exon 2 of GCMB was identified in both affected individuals that changes cysteine at position 106 of the putative DNA-binding domain of GCMB to arginine (C106R). METHODS: We performed mutational analysis of the genes encoding GCMB, pre-pro PTH, GATA3 and CaSR using polymerase chain reaction (PCR)-amplified genomic DNA. The identified GCMB mutant was characterized by functional studies including nuclear localization, electrophoretic mobility shift assays (EMSA) and luciferase reporter assays, and homology modelling was performed to generate a three-dimensional structural model for the DNA-binding domain of GCMB to predict the structural consequences of the identified mutation. RESULTS: The C106R mutant of GCMB failed to interact with the DNA consensus recognition motif, as determined by EMSA. Furthermore, in comparison with wild-type GCMB, the C106R mutant demonstrated reduced transactivation in luciferase reporter assays; however, the mutant GCMB failed to reduce the activity of the wild-type protein. Consistent with the EMSA findings, homology modelling analysis suggested that replacement of cysteine 106 with arginine would interfere with DNA binding. CONCLUSIONS: We have identified a novel GCMB mutation that may explain AD-HP in our family. However, the exact mechanism by which this heterozygous mutation leads to the disease in the described family remains to be elucidated. PMID- 22066719 TI - Impact of post-transplant anemia on patient and graft survival rates after kidney transplantation: a meta-analysis. AB - The impact of post-kidney transplant anemia (PTA) on patient and graft survival rates remains controversial. We performed a meta-analysis to evaluate its impact in causing death of a patient with a functioning graft (DPWFG) and death-censored graft loss (DCGL). A systematic review of 11 observational studies (11,632 kidney transplant patients) that reported the impact of PTA or hemoglobin (Hb) level on these endpoints was performed. Using the World Health Organization (WHO) definition (Hb <12 g/dL in women and Hb <13 g/dL in men), PTA was not associated with DPWFG when results were expressed as an adjusted hazard ratio (aHR: 1.23 [0.97-1.57]), but was associated with higher DPWFG when results were expressed as unadjusted rates (aHR: 2.48 [1.36-4.52]) and when cut-off level for anemia was lower than the WHO definition (aHR: 3.12 [1.92-5.07]). A -1 g/dL decrease in Hb level was associated with higher DPWFG rates (aHR: 1.19 [1.12-1.26]). Using WHO criteria, PTA was associated with higher DCGL rates when results were expressed as aHR (aHR: 1.53 [1.26-1.85]) or as unadjusted rates (aHR: 3.55 [2.36-5.33]); a 1 g/dL decrease in Hb level was associated with higher DCGL rates (aHR: 1.14 [1.11-1.16]). This meta-analysis reveals that the association between PTA and DPWFG varies with PTA definition and adjustment for confounders. In all sub-meta analyses, PTA was significantly associated with DCGL. PMID- 22066720 TI - Optical bifunctionality of europium-complexed luminescent graphene nanosheets. AB - Graphene is an intriguing two-dimensional material, which could be modified for achieving tunable properties with many applications. Photoluminescence of graphene due to plasmonic emission is well-known, however, attempts to develop strong luminescent graphene have been difficult. Synthesis of a graphene-based material with a dual optical functionality, namely quenching the fluorescence of organic dyes while maintaining its own self-luminescence, is an interesting and challenging proposition. Here, we demonstrate this optical bifunctionality in a lattice-modified luminescent graphene, where europium(III) cations are complexed with graphene through oxygen functionalities. After excitation at 314 nm, a hypersensitive red emission is observed at 614 and 618 nm showing the complexation of europium(III) with graphene. We demonstrate dual functionality of this graphene by the quenching of luminescence of Rhodamine-B while displaying its own hypersensitive red emission. The decay lifetime observed through the time resolved spectroscopy confirms its potential for applications in biosensing as well as optoelectronics. PMID- 22066721 TI - Anaerobic naphthalene degradation by Gram-positive, iron-reducing bacteria. AB - An anaerobic naphthalene-degrading culture (N49) was enriched with ferric iron as electron acceptor. A closed electron balance indicated the total oxidation of naphthalene to CO(2). In all growing cultures, the concentration of the presumed central metabolite of naphthalene degradation, 2-naphthoic acid, increased concomitantly with growth. The first metabolite of anaerobic methylnaphthalene degradation, naphthyl-2-methyl-succinic acid, was not identified in culture supernatants, which does not support a methylation to methylnaphthalene as the initial activation reaction of naphthalene, but rather a carboxylation, as proposed for other naphthalene-degrading cultures. Substrate utilization tests revealed that the culture was able to grow on 1-methyl-naphthalene, 2-methyl naphthalene, 1-naphthoic acid or 2-naphthoic acid, whereas it did not grow on 1 naphthol, 2-naphthol, anthracene, phenanthrene, indane and indene. Terminal restriction fragment length polymorphism and 16S rRNA gene sequence analyses revealed that the microbial community of the culture was dominated by one bacterial microorganism, which was closely related (99% 16S sequence similarity) to the major organism in the iron-reducing, benzene-degrading enrichment culture BF [ISME J (2007) 1: 643; Int J Syst Evol Microbiol (2010) 60: 686]. The phylogenetic classification supports a new candidate species and genus of Gram positive spore-forming iron-reducers that can degrade non-substituted aromatic hydrocarbons. It furthermore indicates that Gram-positive microorganisms might also play an important role in anaerobic polycyclic aromatic hydrocarbon degradation. PMID- 22066723 TI - Reviews on animal diseases recently published in other journals. PMID- 22066722 TI - Nutrition and division of labor: Effects on foraging and brain gene expression in the paper wasp Polistes metricus. AB - Deeply conserved molecular mechanisms regulate food-searching behaviour in response to nutritional cues in a wide variety of vertebrates and invertebrates. Studies of the highly eusocial honey bee have shown that nutritional physiology and some conserved nutrient signalling pathways, especially the insulin pathway, also regulate the division of labour between foraging and non-foraging individuals. Typically, lean workers leave the nest to forage for food, and well nourished workers perform tasks inside the nest. Here we provide the first direct test of whether similar mechanisms operate in a primitively eusocial insect in an independently evolved social lineage, the paper wasp Polistes metricus. We found that food deprivation caused reduced lipid stores and higher levels of colony and individual foraging. Individuals with greatly reduced lipid stores foraged at extremely elevated levels. In addition, brain expression of several foraging related genes was influenced by food deprivation, including insulin-like peptide 2 (ilp2). Together with previous findings, our results demonstrate that nutrition regulates foraging division of labour in two independently evolved social insect lineages (bees and wasps), despite large differences in social organization. Our results also provide additional support for the idea that nutritional asymmetries among individuals, based on differences in nutritional physiology and expression of conserved nutrient signalling genes in the brain, are important in the division of labour in eusocial societies. PMID- 22066725 TI - Influence of gastric acid on gastric emptying and gastric distension-induced pain response in rats--effects of famotidine and mosapride. AB - BACKGROUND: Gastroduodenal acidification has been reported to aggravate upper abdominal discomfort and pain that are symptoms suffered by functional dyspepsia (FD) patients. Delayed gastric emptying and hypersensitivity to gastric distension (GD) contribute importantly to the pathophysiology of FD. METHODS: In the present study, we determined the influence of pentagastrin-stimulated endogenous gastric acid on gastric emptying and GD-induced pain responses using rat model systems. Moreover, we evaluated the effects of famotidine and mosapride on changes in gastric emptying and the GD-induced pain response to gastric acid hypersecretion. Gastric emptying was measured by excretion of glass beads that had been intragastrically administered with a liquid nutrient, and gastric pain response was evaluated by observing whether a GD-induced increase in mean blood pressure occurred. KEY RESULTS: Pentagastrin (2 mg kg(-1), s.c.) which markedly and continuously stimulated gastric acid secretion, significantly delayed and enhanced respectively, gastric emptying and pain compared with saline-injected groups. Oral famotidine (0.1-3 mg kg(-1)) and mosapride (0.3-3 mg kg(-1)) administration in a dose-dependent manner accelerated the delay of gastric emptying. Furthermore, famotidine (0.3-3 mg kg(-1)) significantly alleviated the aggravation of the GD-induced pain response, but mosapride (10 mg kg(-1)) did not. CONCLUSIONS & INFERENCES: We established rat models to evaluate the effect of gastric acid hypersecretion on gastric emptying and the GD-induced pain response. In these models, acid hypersecretion delayed gastric emptying and aggravated the pain response. Furthermore, we showed that famotidine ameliorated both delayed gastric emptying and gastric hypersensitivity, whereas mosapride only improved delayed gastric emptying. PMID- 22066734 TI - Relationship between NF-kappaB1 and NF-kappaBIA genetic polymorphisms and Crimean Congo hemorrhagic fever. AB - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is an acute viral hemorrhagic fever caused by the Crimean-Congo hemorrhagic fever virus (CCHFV). Nuclear factor (NF)-kappaB regulates the expression of hundreds of genes, including inflammatory and immunoregulatory, cell cycle regulating, and anti-apoptotic genes. NF kappaBIA (IkappaBalpha) encodes an inhibitory version of the NF-kappaB proteins. METHODS: This study is the first to investigate the association between NF kappaB1 - 94W/D and NF-kappaBIA 3->UTR A->G polymorphisms and CCHF using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: There was a significant difference in NF-kappaB1 - 94W/D genotype distribution between CCHF patients and control populations (p = 0.001). Comparison of the WW genotype with both WD and DD genotypes revealed that the difference between CCHF patients and controls was statistically significant (p = 0.043 for WD genotype, p = 0.018 for DD genotype). However, a significant deviation was found between patients with fatal CCHF and control populations (p = 0.025). The results show that patients with fatal CCHF with the DD genotype have a 4.06-times higher risk for CCHF compared to patients in the control group (odds ratio (OR) 4.06, 95% confidence interval (CI) 1.11-14.87). A significant difference in NF-kappaBIA 3->UTR A->G polymorphisms was observed between CCHF patients and controls in both AA vs AG and AA vs GG (OR 2.04, p = 0.019; OR 2.01, p = 0.049, respectively). CONCLUSIONS: Our findings suggest that NF-kappaB1 - 94W/D and NF-kappaBIA 3->UTR A->G polymorphisms may be valuable predictors of the clinical course in CCHF disease. PMID- 22066735 TI - An adaptive governance approach to disaster-related behavioural health services. AB - This paper explores the provision of disaster-related behavioural and mental health (DBH) services as a problem of institutional collective action in the United States. This study reviews the challenges that providers have in surmounting multi-organizational disconnects, unstable professional legitimacy, ambiguous information, and shifting disaster needs in developing a system for delivering DBH services. Based on the adaptive governance framework, it argues that existing protocols such as the National Incident Management System (NIMS) and Incident Command System (ICS) may be helpful in advancing collective action, but that real progress will depend on a recognition of norms, expectations, and credentials across many spheres-in other words, on the ability of responders to continuously adjust their procedures and administrative boundaries for behavioural health institutions. PMID- 22066736 TI - Evolutionary conservation of the tissue factor disulfide bonds and identification of a possible oxidoreductase binding motif. PMID- 22066737 TI - Carotid intima-media thickness measurements are not affected by the ultrasound frequency. AB - OBJECTIVE: Carotid intima-media thickness (IMT) is a B-mode ultrasound measure of subclinical atherosclerosis predictive of future cardiovascular risk. Carotid IMT measurements were historically obtained at an ultrasound frequency of 8 MHz or lower, but it is unknown whether measurements obtained at higher frequencies using newer, more advanced ultrasound technology allow for valid comparison to the older general population databases that are commonly used for the interpretation of carotid IMT results. METHODS: Carotid IMT studies were conducted in 35 consecutive patients at standard (8 MHz) and high (14 MHz) frequencies and measurements were performed by two independent expert readers. Systematic bias was assessed by using the paired t-test and agreement was analyzed with the Bland-Altman method. RESULTS: The sample mean carotid IMT obtained at 14 MHz was 0.006 mm lower than that obtained at 8 MHz. The 95% confidence interval (CI) for the mean difference between frequencies indicated that the population mean for 14 MHz is unlikely to be more than 0.02 mm lower than for 8 MHz (95% CI -0.017 to 0.004). The 95% reference range for the difference between the two transducer frequencies indicated that the thickness obtained at 14 MHz was within 0.05 mm of that obtained at 8 MHz for 95% of subjects. CONCLUSIONS: Carotid IMT measurements obtained at higher transducer frequencies are similar to those obtained at standard frequency. This finding has important clinical implications because it validates comparison of carotid IMT measurements obtained with newer, more advanced ultrasound technology with the landmark reference carotid IMT studies commonly used for interpretation of carotid IMT results. PMID- 22066738 TI - Comparison of annular diffusion denuder and high volume air samplers for measuring per- and polyfluoroalkyl substances in the atmosphere. AB - Overestimation of the particle phase concentration collected on glass-fiber filters (GFFs) has been reported for perfluoroalkyl carboxylic acids (PFCAs) using conventional high volume air samplers. In this study, per- and polyfluoroalkyl substances (PFASs) were determined in the gas and particulate phases using colocated annular diffusion denuder and high volume air samplers at a semiurban site in Toronto, Canada, in winter 2010. Samples were analyzed for 7 PFAS classes (i.e., PFCAs, perfluoro-alkane sulfonic acids (PFSAs), fluorotelomer alcohols (FTOHs), fluorotelomer methacrylates (FTMACs), fluorotelomer acrylates (FTACs), perfluorooctane sulfonamides (FOSAs), and perfluorooctane sulfonamidoethanols (FOSEs)). The gas diffusion coefficients for individual PFASs were calculated and the denuder performance was evaluated. Modeled subcooled liquid vapor pressures (p(L)) correlated well with the vapor phase breakthrough for the denuder and high volume air systems. Total air concentrations for PFASs measured using annular diffusion denuders and high volume samplers were in agreement within a factor of 4; however, much greater differences were observed for measurements of gas-particle partitioning. Vapor phase PFSAs and PFCAs can adsorb to the GFF using high volume air samplers, resulting in much higher particle-associated fractions for these chemicals compared to the annular diffusion denuder sampler. This effect was not observed for the FTOHs, FTMACs, FTACs, FOSAs, and FOSEs. Thus, for investigations of gas-particle partitioning of PFSAs and PFCAs, the diffusion denuder sampler is the preferred method. The results of this study improve our understanding of the gas-particle partitioning of PFASs, which is important for modeling their long-range transport in air. PMID- 22066739 TI - Enhanced field-emission from SnO2:WO(2.72) nanowire heterostructures. AB - The field-emission properties of SnO(2):WO(2.72) hierarchical nanowire heterostructure have been investigated. Nanoheterostructure consisting of SnO(2) nanowires as stem and WO(2.72) nanothorns as branches are synthesized in two steps by physical vapor deposition technique. Their field emission properties were recorded. A low turn-on field of ~0.82 V/MUm (to draw an emission current density ~10 MUA/cm(2)) is achieved along with stable emission for 4 h duration. The emission characteristic shows the SnO(2):WO(2.72) nanoheterostructures are extremely suitable for field-emission applications. PMID- 22066740 TI - "It is about taking grips and not let myself be ravaged by my body": a qualitative study of outcomes from in-patient multidisciplinary rehabilitation for patients with chronic rheumatic diseases. AB - PURPOSE: To explore how patients experience the process and personal impact of deriving outcomes from a rheumatological rehabilitation program. METHODS: Semi structured interviews were conducted with 23 patients with inflammatory rheumatic diseases approximately 2 months after a 4-week hospital based multidisciplinary rehabilitation program. A thematic analysis was applied. RESULTS: Overarching themes were increased dignity and self-respect. Initial uncertainty regarding illness management was exchanged with confident coping and of becoming an active agent in ones own life. Strategies and coping tools tried out during the rehabilitation stay, do by their experienced effect become primary sources of gained insight into illness and symptom manifestation. Both elements give a sense of control and influence self-confidence and motivation to engage in self management. The process from gained insight and experienced effect of coping tools, to active self management, is however, not automatic. Psychological factors play a key role, and there is a need to take individual psychological themes into account and tailor interventions accordingly. CONCLUSIONS: Specialized multidisciplinary rehabilitation is an ongoing active process, in which psychological factors play a key role and must be accounted for. Well targeted rehabilitation has the potential to create outcomes of major personal impact. PMID- 22066741 TI - Interstitial flow, zebrafish, and lymphatic vascular development. PMID- 22066742 TI - Mesenteric lymph flow in endotoxemic guinea pigs. AB - BACKGROUND: Lipopolysaccharide (LPS) is a structural component of the outer membrane of gram-negative bacteria. LPS activates the host cells, leading to the production and release of proinflammatory cytokines. Given the induction duration for the release of cytokines, the initial mechanisms that produce LPS action on a timescale of minutes are not fully understood. We studied the effect of initial LPS-induced action on the lymphatic system by measuring the time-dependent changes in mesenteric lymph flow in guinea pigs in vivo. In addition, we determined the leakage of plasma protein into the lymphatic system using Evans blue dye. METHODS AND RESULTS: The mesenteric lymphatic vessel was cannulated with a polyethylene catheter. We administered drugs via a catheter in jugular vein. The control animals received vehicle intravenously (i.v.). The experimental group received 1 mg/kg or 10 mg/kg LPS i.v. Twenty minutes before injection of the vehicle or LPS, Evans blue dye (5 mg/kg i.v.) was administered. Lymph output was measured every 20 min. The amount of Evans blue in the lymph was determined by spectrophotometry. The mesenteric lymph showed a steady flow rate of approximately 290 MUL/kg/20 min. The lymph flow immediately increased after the administration of LPS and reached 3.4-fold and 7.4-fold after 1 h of 1 mg/kg and 10 mg/kg LPS injection, respectively. The albumin content in lymph significantly increased in proportion to the increased lymph volume. CONCLUSIONS: These results suggest that the early increase in mesenteric lymph flow rate in guinea pigs produced by LPS is mediated by vascular hyperpermeability and plasma albumin leakage. PMID- 22066743 TI - Prevalence and prognostic significance of secondary lymphedema following breast cancer. AB - BACKGROUND: The adverse consequences of lymphedema following breast cancer in relation to physical function and quality of life are clear; however, its potential relationship with survival has not been investigated. Our purpose was to determine the prevalence of lymphedema and associated upper-body symptoms at 6 years following breast cancer and to examine the prognostic significance of lymphedema with respect to overall 6-year survival (OS). METHODS AND RESULTS: A population-based sample of Australian women (n = 287) diagnosed with invasive, unilateral breast cancer was followed for a median of 6.6 years and prospectively assessed for lymphedema (using bioimpedance spectroscopy [BIS], sum of arm circumferences [SOAC], and self-reported arm swelling), a range of upper-body symptoms, and vital status. OS was measured from date of diagnosis to date of death or last follow-up. Kaplan-Meier methods were used to calculate OS and Cox proportional hazards models quantified the risk associated with lymphedema. Approximately 45% of women had reported at least one moderate to extreme symptom at 6.6 years postdiagnosis, while 34% had shown clinical evidence of lymphedema, and 48% reported arm swelling at least once since baseline assessment. A total of 27 (9.4%) women died during the follow-up period, and lymphedema, diagnosed by BIS or SOAC between 6-18 months postdiagnosis, predicted mortality (BIS: HR = 2.5; 95% CI: 0.9, 6.8, p = 0.08; SOAC: 3.0; 95% CI: 1.1, 8.7, p = 0.04). There was no association (HR = 1.2; 95% CI: 0.5, 2.6, p = 0.68) between self-reported arm swelling and OS. CONCLUSIONS: These findings suggest that lymphedema may influence survival following breast cancer treatment and warrant further investigation in other cancer cohorts and explication of a potential underlying biology. PMID- 22066744 TI - Expression of angiogenic and vasculogenic factors in human lymphedematous tissue. AB - BACKGROUND: Lymphedema is the progressive distention of tissue due to lymphatic dysfunction. The affected area enlarges over time because of fibroadipose deposition, causing morbidity. Because increasing tissue mass requires neovascularization, we hypothesized that angiogenesis or vasculogenesis might be upregulated in lymphedema. METHODS AND RESULTS: Lymphedematous tissue was collected prospectively from nine patients after resection: upper extremity (n = 1), lower extremity (n = 3), penis/scrotum (n = 5). Neovascularization was compared to normal tissue. Specimens were analyzed using immunohistochemistry for alpha-smooth muscle actin (pericyte marker), CD31 (microvascular density), CD31/Ki67 (proliferating endothelial cells), and CD34/CD133 (endothelial progenitor cells). Quantitative real-time PCR (qRT-PCR) was used to determine mRNA expression of progenitor cells (CD133) and factors that recruit them: vascular endothelial growth factor-A (VEGF-A), hypoxia-inducible factor 1alpha (HIF-1alpha), matrix metalloproteinase-9 (MMP-9), and stromal-cell derived factor 1alpha (SDF-1alpha). Angiopoetin-1,-2 (ANG-1,-2), matrix metalloproteinase-2 (MMP 2), and VEGF receptors (VEGFR1,2) were quantified using qRT-PCR. There was no difference in microvascular density, pericytic density, or endothelial proliferation between lymphedematous and normal tissue (p = 0.1). Endothelial progenitor cells were not present in lymphedema or normal specimens (p < 0.01). VEGF-A (1.3-fold), HIF-1alpha (0.8-fold), SDF-1alpha (2.1-fold), VEGFR2 (0.09 fold), and CD133 (0.02-fold) expression were not elevated compared to normal tissue (p = 0.1). ANG-1 (5.6-fold), ANG-2 (2.5-fold), MMP-2 (3.9-fold), MMP-9 (33.4-fold), and VEGFR1 (12.8-fold) mRNA was increased in lymphedematous specimens compared to control (p < 0.05). CONCLUSIONS: Lymphedematous tissue does not exhibit upregulation of angiogenesis or vasculogenesis. Neovascularization is unlikely to be involved in the pathogenesis of this disease. PMID- 22066745 TI - Normal interstitial flow is critical for developmental lymphangiogenesis in the zebrafish. AB - BACKGROUND: The lymphatic system plays a critical role in the body's fluid and protein homeostasis, immune regulation, and dietary fat absorption. One of the major pathologies of the lymphatic system is primary lymphedema, which occurs in approximately 0.6% of live births and is caused by missing or impaired lymphatic vessels. Although there is a great need for medical intervention into diseases of the lymphatic system, very little is known about its development or how it maintains integrity over time. Recent studies have suggested that biophysical components, such as local extracellular fluid flow, may be important factors during initiation of lymphangiogenesis. We hypothesize that interstitial fluid flow functions as an important morphoregulator during developmental lymphangiogenesis. METHODS AND RESULTS: In the present study we use pharmacological agents and a mutant fish line to modulate interstitial flow. Our data confirm that a sufficient increase or decrease in interstitial flow can profoundly affect lymphatic patterning and may result in a lymphedema-like phenotype. Proper interstitial flow appears to be necessary during LEC migration for proper lymphatic development. CONCLUSIONS: These results support the contention that interstitial flow is an important morphoregulator of developmental lymphangiogenesis. PMID- 22066746 TI - Surgical management of lymphedema: past, present, and future. AB - Recent advances in surgical management of lymphedema have provided options for patients who have failed conservative management with manual lymphatic massage and/or compression garments. The purpose of this review is to provide a historical background to the surgical treatment of lymphedema and how these options have evolved over time. In addition, we aim to delineate the various types of surgical approaches available, indications for surgery, and reported outcomes. Our goal is to increase awareness of these options and foster research to improve their outcomes. PMID- 22066750 TI - Glycolaldehyde as a probe molecule for biomass derivatives: reaction of C-OH and C?O functional groups on monolayer Ni surfaces. AB - Controlling the activity and selectivity of converting biomass derivatives to syngas (H(2) and CO) is critical for the utilization of biomass feedstocks as renewable sources for chemicals and fuels. One key chemistry in the conversion is the selective bond scission of the C-OH and C?O functionalities, which are present in many biomass derivatives. Because of the high molecular weight and low vapor pressure, it is relatively difficult to perform fundamental surface science studies of C6 sugars, such as glucose and fructose, using ultrahigh vacuum techniques. Glycolaldehyde (HOCH(2)CH?O) is the smallest molecule that contains both the C-OH and C?O functional groups, as well as the same C/O ratio as C6 sugars, and thus is selected as a probe molecule in the current study to determine how the presence of the C?O bond affects the reaction mechanism. Using a combination of density functional theory calculations and experimental measurements, our results indicate that the reaction pathway of glycolaldehyde to produce syngas can be enhanced by supporting monolayer Ni on a Pt substrate, which shows higher activity than either of the parent metals. Furthermore, the Pt substrate can be replaced by tungsten monocarbide to achieve similar activity and selectivity, indicating the possibility of using Ni/WC to replace Ni/Pt as active and selective catalysts with higher stability and lower cost. PMID- 22066751 TI - Screening for addictive disorders within a workers' compensation clinic: an exploratory study. AB - We conducted a cross-sectional study investigating the extent of addictive disorders within a workers' compensation (WC) clinic. We also examined the feasibility of substance abuse screening within the same clinic. In 2009 , 100 patients were asked to complete the World Health Organization's Alcohol, Smoking, Substance Involvement Screening Test (WHO-ASSIST) and the Current Opioid Misuse Measure (COMM). According to the WHO-ASSIST, we found that 46% of WC patients required intervention for at least one substance-related disorder (25% tobacco, 23% sedatives, 8% opioids), and according to the COMM, 46% screened positive for prescription opioid misuse. Importantly, the addition of this screening was brief, economical, and well accepted by patients. Further research should analyze the costs and benefits of detection and intervention of substance-related disorders in this setting. PMID- 22066752 TI - Effects of phytoestrogens derived from soy bean on expression of adhesion molecules on HUVEC. AB - BACKGROUND: The risks of hormone replacement therapy have led to a search for new alternatives such as phytoestrogens, plant compounds with estrogen-like biological activity. Isoflavones are the phytoestrogens most extensively studied and can be found in soybean, red clover and other plants. Due to this estrogen like activity, phytoestrogens can have some effect on atherosclerosis. Human umbilical vein endothelial cells (HUVEC) have been extensively used to study the biology and pathobiology of human endothelial cells and most of the knowledge acquired is due to experiments with cultures of these cells. OBJECTIVE: To evaluate the effects of the phytoestrogen extracts from Glycine max soy bean, genistein, formononetin, biochanin A and daidzein, as well as a mixture of these extracts (Mix), on expression of adhesion molecules, VCAM-1, ICAM-1 and E selectin, by endothelial cell HUVEC, stimulated with lipopolysaccharide. METHODS: HUVEC were cultured in medium EBM(2), pretreated with isoflavones for 24 and 48 h and then stimulated with lipopolysaccharide; in addition, isoflavones were added, after stimulation by lipopolysaccharide, to HUVEC. We evaluated the production of VCAM-1, ICAM-1 and E-selectin on cell surface, by cell-based enzyme immunoassay, and of sVCAM-1, sICAM-1 and sE-selectin in culture supernatant, by ELISA. RESULTS: Genistein, formononetin, biochanin A and daidzein, as well as the Mix were able to reduce VCAM-1, ICAM-1 and E-selectin on cell surface and in culture supernatant. Conclusion Isoflavones extracted from Glycine max soy bean, in vitro, presented antiatherogenic effects, reducing the expression of adhesion molecules and acting as preventive agents as well as therapeutic agents. PMID- 22066753 TI - Behavior of protein in the presence of calcium during heating of whey protein concentrate solutions. AB - The effect of added CaCl(2) on heat-induced changes in whey protein (WP) solutions prepared from whey protein isolate (WP1), acid whey protein concentrate (WP2), and cheese whey protein concentrate (WP3) was investigated. The loss of native-like, proteins, aggregation, and gel firmness of WP were maximum at certain levels of added CaCl(2). These levels were different for different WP products. The effect of added CaCl(2) on these changes appeared to be related to the initial calcium concentrations of these solutions. The higher the calcium content of the product, the less available sites for added CaCl(2) to bind. It was considered that addition of CaCl(2) changed the types of protein interactions that formed the protein aggregates during heating. Added calcium caused dramatic decreases in fracture stress of WP gels due to the formation of large protein aggregates. PMID- 22066754 TI - Does the EQ-5D reflect lost earnings? AB - BACKGROUND: An important methodological issue in economic evaluations of healthcare is how to include productivity costs (the costs related to reduced productivity due to illness, disability and premature death). Traditionally, they were included in the numerator of a cost-effectiveness analysis, through either the human-capital or the friction-cost method. It has been argued, however, that productivity costs are already included in the denominator (i.e. in the QALY measure) because respondents consider the effect a given health state will have on their income when valuing health states. If that is the case, many previous economic evaluations might have double counted productivity costs by including them in both the numerator and the denominator. AIM: The aim of this study was to determine whether respondents valuing EQ-5D health states using the time trade off (TTO) method spontaneously consider income effects, whether this consideration influences subsequent valuations and whether explicit ex post instructions influence valuations. METHODS: Through an online survey, we asked 321 members of the Dutch general population to value four EQ-5D health states through three different TTO exercises. The first exercise was a standard TTO question. Respondents were then asked whether they had included income effects. Depending on their answer, the second TTO exercise instructed them to either include or exclude income effects. The third TTO exercise provided explicit information regarding the income loss associated with the health state. RESULTS: Data were available from 321 members of the Dutch general public. Of these respondents, 49% stated they had spontaneously included income effects. Twenty five percent of the sample did not trade any time in any of the TTO exercises and these respondents were excluded from the analysis. Results of t-tests showed there were only weakly significant differences in valuations for one health state between those who spontaneously included income effects and those who did not. Explicit instruction led to some significant differences at the aggregate level, but the effect was inconsistent at the individual level. When explicit information on the amount of income loss was provided, all states were valued lower when associated with a larger income loss. CONCLUSIONS: This study offers further evidence indicating that income losses do not significantly affect health state valuations. PMID- 22066755 TI - Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21 hydroxylase autoantibodies. AB - CONTEXT: Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. OBJECTIVE: To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. DESIGN, SETTING AND PARTICIPANTS: Individuals were screened for 21OH AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. MAIN OUTCOME MEASURED: Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. RESULTS: Compared with nonprogressors, in the time period 2 months-2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11-22 pM, P < 1E-4), with no significant differences in mean PRA (P = 0.07) or baseline cortisol (P = 0.08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). CONCLUSION: Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months-2 years preceding the onset of AD. PMID- 22066756 TI - Acute kidney injury as defined by the RIFLE criteria is a risk factor for kidney transplant graft failure. AB - Acute kidney injury (AKI) is not recognized as a major complication at the maintenance phase after kidney transplantation (KTx). Moreover, it is not clear whether the onset of AKI leads to graft failure. We examined the incidence of AKI that developed three months or later after KTx at our institute. We examined whether the incidence of AKI defined by the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage kidney disease criteria associates with graft failure by matched-pair Cox regression analysis. A total of 289 patients were available for the final analysis. The overall incidence of AKI was 20.4%, and the common etiology of AKI was bacterial infectious diseases. The group that developed AKI had significantly lower graft survival than non-AKI group independently of acute rejection. AKI Risk represented a high risk for graft failure and AKI Injury/Failure represented a higher risk for graft failure. The analysis by the AKIN classification yielded the similar results. These results indicate that AKI is a relatively common complication of KTx and represents the major risk for graft failure. We should make every effort in the prevention and early detection to avoid the occurrence of AKI and the subsequent graft failure after KTx. PMID- 22066757 TI - Effects of poly-beta-hydroxybutyrate (PHB) on Siberian sturgeon (Acipenser baerii) fingerlings performance and its gastrointestinal tract microbial community. AB - Poly-beta-hydroxybutyrate (PHB) is a natural polymer that can be depolymerized into water-soluble short-chain fatty acid monomers. These monomers can act as microbial control agents. In this study, the effects of partially replacing the diet of Siberian sturgeon fingerlings with 2% and 5% PHB were investigated. Replacing 2% of the diet with PHB improved weight gain, specific growth rate (SGR) and survival in the sturgeon fingerlings during the 10-week experimental period. Community-level physiological profiling and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) were used to analyze the microbial community diversity and community organization in the sturgeon gastrointestinal tract. DGGE analysis revealed that PHB affected the intestinal microbial species richness and diversity. The highest species richness was observed with 2% PHB. DNA sequencing of the dominant bands in 2% and 5% PHB treatments revealed that PHB stimulated bacteria belonging to the genera Bacillus and Ruminococcaceae. Principal component analysis, Lorenz curves and the Shannon index of Biolog Ecoplate data revealed that aerobic metabolic potential of the bacterial community was different in the PHB-treated fishes as compared with the control situation. Overall, our results indicate that PHB act as microbial control agents and replacement of 2% of Siberian sturgeon fingerling diet with PHB has beneficial effects. PMID- 22066758 TI - Genetic evidence for multiple events of hybridization between wolves and domestic dogs in the Iberian Peninsula. AB - Hybridization between wild species and their domestic counterparts may represent a major threat to natural populations. However, high genetic similarity between the hybridizing taxa makes the detection of hybrids a difficult task and may hinder attempts to assess the impact of hybridization in conservation biology. In this work, we used a combination of 42 autosomal microsatellites together with Y chromosome microsatellite-defined haplotypes and mtDNA sequences to investigate the occurrence and dynamics of wolf-dog hybridization in the Iberian Peninsula. To do this, we applied a variety of Bayesian analyses and a parallel set of simulation studies to evaluate (i) the differences between Iberian wolves and dogs, (ii) the frequency and geographical distribution of hybridization and (iii) the directionality of hybridization. First, we show that Iberian wolves and dogs form two well-differentiated genetic entities, suggesting that introgressive hybridization is not a widespread phenomenon shaping both gene pools. Second, we found evidence for the existence of hybridization that is apparently restricted to more peripheral and recently expanded wolf populations. Third, we describe compelling evidence suggesting that the dynamics of hybridization in wolf populations is mediated by crosses between male dogs and female wolves. More importantly, the observation of a population showing the occurrence of a continuum of hybrid classes forming mixed packs may indicate that we have underestimated hybridization. If future studies confirm this pattern, then an intriguing avenue of research is to investigate how introgression from free ranging domestic dogs is enabling wolf populations to adapt to the highly humanized habitats of southern Europe while still maintaining their genetic differentiation. PMID- 22066760 TI - European dissertations from 1997 onwards on the viruses and the virus-induced diseases reviewed in the preceding three articles. PMID- 22066759 TI - Equine herpesvirus 1 and 4 infections: An update. AB - Summary Equine herpesvirus 1 (EHV1) and equine herpesvirus 4 (EHV4) are important ubiquitous equine pathogens, causing much damage to the viral horse industry. EHV1 strains are associated with respiratory disease, abortion, and paresis/paralysis, whereas EHV4 strains are predominantly associated with respiratory disease. In the past decades much research effort has been put into improving knowledge about these viruses. In this paper the current state of knowledge of these viruses and the most important aspects of these virus infections, e.g. epidemiology, clinical aspects, pathogenesis and pathology, immunity, diagnosis, preventive management and management in the course of an outbreak and vaccination, is reviewed. Because we performed some research ourselves in the areas of diagnosis, epidemiology and vaccinology these aspects are reviewed in more depth than the other aspects. Still many questions have remained and new questions have risen. Consequently, research priorities should be made in an attempt to answer these questions. Therefore, this review ends with some personal recommendations for important priorities for future research. PMID- 22066761 TI - Reviews on animal diseases recently published in other journals. PMID- 22066763 TI - Fluoroquinolone resistance of Escherichia coli and Salmonella from healthy livestock and poultry in the EU. AB - The potential for transmission of antibiotic-resistant enteric zoonotic bacteria from animals to humans has been a public health concern for several decades. Bacteria carrying antibiotic resistance genes found in the intestinal tract of food animals can contaminate carcasses and may lead to food-borne disease in humans that may not respond to antibiotic treatment. It is consequently important to monitor changes in antimicrobial susceptibility of zoonotic and commensal organism; in this context, there are a number of veterinary monitoring programmes that collect bacteria in food-producing animals at slaughter and determine their susceptibility against antibiotics relevant for human medicine. The data generated are part of the risk analysis for potential food-borne transmission of resistance. There has been much debate about the use of fluoroquinolones in veterinary medicine, and so, this review will consider the fluoroquinolone data from two surveys and compare them to national surveillance programmes. At the outset, it must be pointed out that there is, however, a lack of agreement between several programmes on what is meant by the term 'fluoroquinolone resistance' through use of different definitions of resistance and different resistance breakpoints. An additional aim of this paper is to clarify some of those definitions. Despite the debate about the contribution of antibiotic use in veterinary medicine to the overall resistance development in human pathogens, the data suggest that clinical resistance to fluoroquinolones in Escherichia coli and nontyphoidal Salmonella is generally uncommon, except for a few countries. Ongoing surveillance will continue to monitor the situation and identify whether this situation changes within the respective animal populations. For the benefit of both the epidemiologist and the clinician, it would be strongly advantageous that national monitoring surveys report both percentages of clinical resistance and decreased susceptibility. PMID- 22066764 TI - Fatty acid profile and influence of oxythiamine on fatty acid content in Malassezia pachydermatis, Candida albicans and Saccharomyces cerevisiae. AB - Malassezia pachydermatis and Candida albicans are fungi involved in the skin diseases and systemic infections. The therapy of such infections is difficult due to relapses and problems with pathogen identification. In our study, we compare the fatty acids profile of M. pachydermatis, C. albicans and S. cerevisiae to identify diagnostic markers and to investigate the effect of oxythiamine (OT) on the lipid composition of these species. Total fatty acid content is threefold higher in C. albicans and M. pachydermatis compared with S. cerevisiae. These two species have also increased level of polyunsaturated fatty acids (PUFA) and decreased content of monounsaturated fatty acids (MUFA). We noted differences in the content of longer chain (>18) fatty acids between studied species (for example a lack of 20 : 1 in S. cerevisiae and 22 : 0 in M. pachydermatis and C. albicans). OT reduces total fatty acids content in M. pachydermatis by 50%. In S. cerevisiae, OT increased PUFA whereas it decreased MUFA content. In C. albicans, OT decreased PUFA and increased MUFA and SFA content. The results show that the MUFA to PUFA ratio and the fatty acid profile could be useful diagnostic tests to distinguish C. albicans, M. pachydermatis and S. cerevisiae, and OT affected the lipid metabolism of the investigated species, especially M. pachydermatis. PMID- 22066775 TI - Diversity of extended-spectrum beta-lactamase-producing Enterobacteriaceae on hospital admission. AB - Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have become prevalent in both the hospital and the community. We describe the epidemiology of ESBL-producing isolates and patient characteristics at hospital admission. Data on clinical properties, medical history, previous hospitalizations, and previous antibiotic treatments were collected. ESBL genes (bla(CTX-M), bla(TEM), and bla(SHV)) were identified by polymerase chain reaction. One hundred and sixteen patients carried 122 ESBL-producing Enterobacteriaceae: 79 Escherichia coli, 26 Klebsiella pneumoniae, 16 Enterobacter spp., and 1 Citrobacter koseri. ESBL producing E. coli were associated with admission from home (odds ratio (OR) 3.04, p = 0.02) and a history of recent urinary tract infection (OR 3.38, p = 0.04), and exhibited a lower rate of antimicrobial resistance to aminoglycosides (p <= 0.005) and co-trimoxazole (p = 0.003), whereas other ESBL-producing Enterobacteriaceae tended to be associated with a recent surgery (OR 0.42, p = 0.057). Although the CTX-M enzymes were more frequently found in E. coli (76%), they were also identified in other Enterobacteriaceae (45%), suggesting penetration of CTX-M-type enzymes into both community- and hospital-acquired enterobacterial species. PMID- 22066776 TI - Tryptose phosphate broth improves Rickettsia felis replication in mammalian cells. AB - In cell culture, Rickettsia felis grows only at low temperatures (< 31 degrees C). Therefore, its ability to enter, survive and grow in cell lines has primarily been tested in cells derived from amphibians and arthropods, which naturally grow at low temperatures, and only infrequently in mammalian cells. We subcultured R. felis in mammalian cells for more than 10 passages using media supplemented with tryptose phosphate broth (TPB) and found that TPB is critical for optimal growth of R. felis in mammalian cells. PMID- 22066777 TI - Communities of purple sulfur bacteria in a Baltic Sea coastal lagoon analyzed by puf LM gene libraries and the impact of temperature and NaCl concentration in experimental enrichment cultures. AB - Shallow coastal waters, where phototrophic purple sulfur bacteria (PSB) regularly form massive blooms, are subjected to massive diurnal and event-driven changes of physicochemical conditions including temperature and salinity. To analyze the ability of PSB to cope with these environmental factors and to compete in complex communities we have studied changes of the environmental community of PSB of a Baltic Sea lagoon under experimental enrichment conditions with controlled variation of temperature and NaCl concentration. For the first time, changes within a community of PSB were specifically analyzed using the photosynthetic reaction center genes pufL and M by RFLP and cloning experiments. The most abundant PSB phylotypes in the habitat were found along the NaCl gradient from freshwater conditions up to 7.5% NaCl. They were accompanied by smaller numbers of purple nonsulfur bacteria and aerobic anoxygenic phototrophic bacteria. Major components of the PSB community of the brackish lagoon were affiliated to PSB genera and species known as marine, halophilic or salt-tolerant, including species of M arichromatium, H alochromatium, T hiorhodococcus, A llochromatium, T hiocapsa, T hiorhodovibrio, and T hiohalocapsa. A dramatic shift occurred at elevated temperatures of 41 and 44 degrees C when M arichromatium gracile became most prominent which was not detected at lower temperatures. PMID- 22066778 TI - Social, not physical, infrastructure: the critical role of civil society after the 1923 Tokyo earthquake. AB - Despite the tremendous destruction wrought by catastrophes, social science holds few quantitative assessments of explanations for the rate of recovery. This article illuminates four factors-damage, population density, human capital, and economic capital-that are thought to explain the variation in the pace of population recovery following disaster; it also explores the popular but relatively untested factor of social capital. Using time-series, cross-sectional models and propensity score matching, it tests these approaches using new data from the rebuilding of 39 neighbourhoods in Tokyo after its 1923 earthquake. Social capital, more than earthquake damage, population density, human capital, or economic capital, best predicts population recovery in post-earthquake Tokyo. These findings suggest new approaches for research on social capital and disasters as well as public policy avenues for handling catastrophes. PMID- 22066779 TI - Air pollution-associated procoagulant changes: the role of circulating microvesicles. AB - BACKGROUND: Epidemiological studies suggest an association between exposure to particulate matter (PM) in air pollution and the risk of venous thromboembolism (VTE). OBJECTIVES: To investigate the underlying pathophysiological pathways linking PM exposure and VTE. PATIENTS AND METHODS: We assessed potential associations between PM exposure and coagulation and inflammation parameters, including circulating microvesicles, in a group of 233 patients with diabetes. RESULTS: The numbers of circulating blood platelet-derived and annexin V-binding microvesicles were inversely associated with the current levels of PM(2.5) or PM(10), measured on the day of sampling. Recent past exposure to PM(10), up to 1 week prior to blood sampling, estimated at the patients' residential addresses, was associated with elevated high-sensitivity C-reactive protein (CRP), leukocytes and fibrinogen, as well as with tissue factor (TF)-dependent procoagulant changes in thrombin generation assays. When longer windows of past exposure were considered, up to 1 year preceding blood sampling, procoagulant changes were evident from the strongly increased numbers of red blood cell derived circulating microvesicles and annexin V-binding microvesicles, but they no longer associated with TF. Past PM exposure was never associated with activated partial thromboplastin time (aPTT), prothrombin time (PT), or factor (F) VII, FVIII, FXII or D-dimers. Residential distance to a major road was only marginally correlated with procoagulant changes in FVIII and thrombin generation. CONCLUSIONS: Increases in the number of microvesicles and in their procoagulant properties, rather than increases in coagulation factors per se, seem to contribute to the risk of VTE, developing during prolonged exposure to air pollutants. PMID- 22066780 TI - Evaluation of right ventricular function in early period following transcatheter closure of atrial septal defect. AB - AIMS: There is limited data on alterations in novel right ventricular (RV) function indices like tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (TASV) after transcatheter atrial septal defect (ASD) closure. We aimed to evaluate RV function by echocardiography (ECG) with these novel indices in early period in patients with secundum-type ASD that was closed percutaneously. METHODS: Patients were enrolled to study if they had secundum-type ASD that was suitable for percutaneous closure. Patient population consisted of 4 men and 16 women. Echocardiography was performed before and 1 month after closure. RESULTS: Mean age was 37 +/- 16. Mean diameter of ASD and total atrial septum length measured by ECG were 19 +/- 6 mm and 49 +/- 7 mm, respectively. Mean diameter of defect in transesophageal echocardiography was 20 +/- 6 mm. Stretched mean diameter in catheterization was 23 +/- 6 mm. One month after closure, there were statistically significant decreases in RV end-diastolic diameters (43.3 +/- 10.7 mm vs. 34.9 +/- 5.5 mm; P < 0.001), RV/left ventricular (LV) end-diastolic diameter ratio (1.1 +/- 0.3 vs. 0.87 +/- 0.1; P < 0.001), TASV (16.9 +/- 3.2 cm/sec vs. 14.3 +/- 3.3 cm/sec; P < 0.05), early diastolic tricuspid annular velocity (15.3 +/- 3.1 cm/sec vs. 13.4 +/- 2.4 cm/sec P <0.05), late diastolic tricuspid annular velocity (16.2 +/- 5.4 cm/sec vs. 14.3 +/- 6.3 cm/sec; P < 0.05), and TAPSE (29.9 +/- 6.2 mm vs. 22.4 +/- 7.4 mm; P < 0.001). LV end-diastolic diameter (38.0 +/- 6.9 mm and 40.0 +/- 4.5 P < 0.05) was increased, whereas there was no change in LV ejection fraction. CONCLUSION: Closure of ASD by using Amplatzer devices led to decrease in right heart chamber size, tissue Doppler-derived tricuspid annular velocities and TAPSE in early period. PMID- 22066781 TI - Chiral separations: a review of current topics and trends. PMID- 22066782 TI - Cheminformatics-driven discovery of selective, nanomolar inhibitors for staphylococcal pyruvate kinase. AB - We have recently mapped the protein interaction network of methicillin-resistant Staphylococcus aureus (MRSA), which revealed its scale-free organization with characteristic presence of highly connected hub proteins that are critical for bacterial survival. Here we report the discovery of inhibitors that are highly potent against one such hub target, staphylococcal pyruvate kinase (PK). Importantly, the developed compounds demonstrate complete selectivity for the bacterial enzyme compared to all human orthologues. The lead 91nM inhibitor IS 130 has been identified through ligand-based cheminformatic exploration of a chemical space around micromolar hits initially generated by experimental screening. The following crystallographic study resulted in identification of a tetrameric MRSA PK structure where IS-130 is bound to the interface between the protein's subunits. This newly described binding pocket is not present in otherwise highly similar human orthologues and can be effectively utilized for selective inhibition of bacterial PK. The following synthetic modifications of IS 130, guided by structure-based molecular modeling, resulted in the development of MRSA PK inhibitors with much improved antimicrobial properties. Considering a notable lack of recent reports on novel antibacterial targets and cognate antibacterial compounds, this study provides a valuable perspective on the development of a new generation of antimicrobials. Equally noteworthy, the results of the current work highlight the importance of rigorous cheminformatics based exploration of the results of high-throughput experiments. PMID- 22066783 TI - PEG-detachable cationic polyaspartamide derivatives bearing stearoyl moieties for systemic siRNA delivery toward subcutaneous BxPC3 pancreatic tumor. AB - For systemic siRNA delivery into tumor tissues, a safe and efficient vehicle is strongly required. Therefore, we designed a block copolymer of detachable poly(ethylene glycol) (PEG) polycation bearing low pKa amines and hydrophobic moieties in the side chain to develop a smart siRNA complex possessing biocompatibility, high complex stability, and endosomal escaping functionality. A disulfide linkage (-SS-) was inserted as a linker between PEG and a cationic polyaspartamide derivative, poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PAsp(DET)), with a flanking stearoyl moiety, where PAsp(DET) segment provides the excellent ability of endosome destabilization by direct interaction with the membrane. The resulting polymer, stearoyl PEG-SS-PAsp(DET), was confirmed to form the siRNA complex with an environment-responsive PEG palisade, which was detached from the complex surface under reductive conditions mimicking tumor tissues and cytoplasm because of the disulfide cleavage. The smart siRNA complex allowed significant gene silencing against cultured pancreatic cancer cells without considerable cytotoxicity and erythrocyte disruption, whereas such significant gene silencing was not observed in a control siRNA complex without the disulfide linkage. This enhanced gene silencing activity might be because of the enhanced cellular uptake and subsequent translocation of siRNA into cytoplasm facilitated by PEG detachment around and/or in the cancer cells. Further, intravital real time confocal laser scanning microscopic observation revealed the effect of hydrophobic stearoyl modification on the stabilization of the siRNA complex for longevity in the blood. Significant in vivo gene silencing of the smart siRNA complex was achieved by systemic administration of vascular endothelial growth factor siRNA in a mouse model bearing a subcutaneous pancreatic tumor, leading to 40% regression in tumor growth. These results demonstrate the strong potential of stearoyl PEG-SS-PAsp(DET) as a vehicle for systemic delivery of siRNA in cancer therapy. PMID- 22066785 TI - Boron cluster-based development of potent nonsecosteroidal vitamin D receptor ligands: direct observation of hydrophobic interaction between protein surface and carborane. AB - We report here the design and synthesis of a novel vitamin D receptor (VDR) agonist whose hydrophobic core structure is p-carborane (1,12-dicarba-closo dodecaborane, an icosahedral carbon-containing boron cluster having remarkable thermal and chemical stability and a characteristically hydrophobic B-H surface). This carborane-based VDR ligand exhibited moderate vitamin D activity, comparable to that of the natural hormone, despite its simple and flexible structure. X-ray structure analysis provided direct evidence that the carborane cage binds to the hydrophobic surface of the ligand-binding pocket of the receptor, promoting transition to the active conformation. These results indicate that the spherical B-H surface of carborane can function efficiently as a hydrophobic anchor in binding to the receptor surface, thereby allowing induced fitting of the three essential hydroxyl groups on the alkyl chains to the appropriate positions for interaction with the VDR binding site, despite the entropic disadvantage of the flexible structure. We suggest that carborane structure is a promising option in the design of novel drug candidates. PMID- 22066784 TI - Inhibition of exocytosis or endocytosis blocks activity-dependent redistribution of synapsin. AB - The synaptic vesicle cycle encompasses the pre-synaptic events that drive neurotransmission. Influx of calcium leads to the fusion of synaptic vesicles with the plasma membrane and the release of neurotransmitter, closely followed by endocytosis. Vacated release sites are repopulated with vesicles which are then primed for release. When activity is intense, reserve vesicles may be mobilized to counteract an eventual decline in transmission. Recently, interplay between endocytosis and repopulation of the readily releasable pool of vesicles has been identified. In this study, we show that exo-endocytosis is necessary to enable detachment of synapsin from reserve pool vesicles during synaptic activity. We report that blockage of exocytosis in cultured mouse hippocampal neurons, either by tetanus toxin or by the deletion of munc13, inhibits the activity-dependent redistribution of synapsin from the pre-synaptic terminal into the axon. Likewise, perturbation of endocytosis with dynasore or by a dynamin dominant negative mutant fully prevents synapsin redistribution. Such inhibition of synapsin redistribution occurred despite the efficient phosphorylation of synapsin at its protein kinase A/CaMKI site, indicating that disengagement of synapsin from the vesicles requires exocytosis and endocytosis in addition to phosphorylation. Our results therefore reveal hitherto unidentified feedback within the synaptic vesicle cycle involving the synapsin-managed reserve pool. PMID- 22066786 TI - Unusual colours of plasma. PMID- 22066787 TI - The major aminoglycoside-modifying enzyme AAC(3)-II found in Escherichia coli determines a significant disparity in its resistance to gentamicin and amikacin in China. AB - The aim of this study was to investigate the prevalence of aminoglycoside modifying enzymes in Escherichia coli in different areas of China and to explore the relationship between pandemic enzyme type and bacterial resistance to antimicrobial agents in China. Gentamicin- or etimicin-resistant clinical isolates of E. coli were collected from different areas of China, and the in vitro antibacterial activity of 11 aminoglycoside agents was determined using standard (Clinical and Laboratory Standards Institute) agar dilution methods. Twelve aminoglycoside-modifying enzyme genes were detected by PCR and confirmed by DNA sequencing. A total of 205 E. coli strains were collected from nine hospitals in seven cities. All strains were highly resistant to gentamicin or etimicin, whereas resistance to tobramycin, netilmicin, and kanamycin was slightly lower. However, less than 15% of isolates were resistant to amikacin and isepamicin. Of the gentamicin-resistant strains, 88.2% and 86.7% were sensitive to isepamicin and amikacin, respectively. Five aminoglycoside-modifying enzyme genes were detected in 191 strains, whereas the remaining 14 strains were negative. The most common gene type was aac(3)-II (162 strains), followed by aac(6')-I (50 strains), ant(3")-I (28 strains), aph(3')-II (20 strains), and ant(2")-I (20 strains). Ninety-five strains yielded aac(3)-II only, whereas the others contained two or three genes. The three main gene combinations were aac(6')-I/aac(3)-II (28 strains), aac(3)-II/ant(3")-I (11 strains), and aac(3) II/aac(6')-I (10 strains). Regional bacterial resistance and enzyme distribution were roughly similar, although minor differences were found in Guangzhou, Jinan, and Dalian, which were the sources of most of the amikacin- or isepamicin resistant strains. Chinese clinical isolates of E. coli remain highly resistant to gentamicin and etimicin, but are susceptible to amikacin and isepamicin. The dominant type of aminoglycoside-modifying enzyme, AAC(3)-II, might be the main source of the disparity in E. coli resistance to different aminoglycoside agents. PMID- 22066788 TI - Association between the androgen levels and erectile function, cognitive functions and hypogonadism symptoms in aging males. AB - PURPOSE: Aging in men is characterized by a moderate decrease in plasma testosterone (T) levels. However, the association between partial androgen deficiency of the aging male and clinical symptoms and the ideal screening test are controversial. In this study, we investigated the association between the androgen levels and erectile function, cognitive functions and hypogonadism symptoms in aging males. MATERIALS AND METHODS: We investigated the association between total (TT), calculated free (FT) and bioavailable (BT) testosterone, and various clinical and laboratory parameters in 103 healthy males, 50-80 years old. Biochemical assessment was done after overnight fasting. Questionnaires were used to test for hypogonadism symptoms, erectile and cognitive functions. RESULTS: TT levels were not correlated with aging in this study. However, FT and BT were found to decrease with age due to rising sex hormone binding globulin. TT levels were strongly correlated with FT and BT levels (respectively p = 0.0001, p = 0.0001). TT, FT and BT were only correlated with cognitive functions (p = 0.012, p = 0.004, p = 0.02 respectively). There was no correlation between TT, FT and BT levels and erectile function and hypogonadism symptoms. CONCLUSION: T values in our study sample did not correlate with clinical signs and symptoms of hypogonadism. Thus, according to our data, symptoms in the aging male should not be indiscriminately assigned to a decrease in TT, FT or BT levels. PMID- 22066789 TI - Hydrodynamic force on a microparticle approaching a wall in a nanoparticle dispersion: observation of a separation-dependent effective viscosity. AB - Colloid probe atomic force microscopy was used to measure the hydrodynamic force exerted on a 30-MUm-diameter silica particle being moved toward or away from a silica plate in aqueous dispersions of 22-nm-diameter silica nanoparticles (6 or 8 vol %). Upon comparing the measured force to predictions made using the well known expression of Cox and Brenner (Cox, R. G.; Brenner, H. Chem. Eng. Sci.1967, 22, 1753-1777) assuming a constant viscosity equal to that of the bulk dispersion, the measured drag force was found to become significantly less than that predicted at smaller particle-plate separation distances (e.g., <500 nm). A recent theoretical paper by Bhattacharya and Blawzdziewicz (Bhattacharya, S.; Blawzdziewicz, J. J. Chem. Phys.2008, 128, 214704) predicted that in a solution of dispersed nanoparticles the effective viscosity characterizing the hydrodynamic force on the particle should vary from that of the solvent at contact to that of the bulk dispersion at large separations. By adjusting the viscosity in the Cox and Brenner expression to make the predicted hydrodynamic force match that measured (i.e., the effective viscosity), a curve showing these exact characteristics was obtained. The effective viscosity profile was not a function of particle speed, and changes in the effective viscosity extended to separation distances of as large as 2 MUm (nearly 100 times the hard diameter of the nanoparticles). These results suggest that in the range of typical colloidal forces (on the order of 100 nm), the dynamics of particle motion in such systems are determined by the viscosity of the solvent and not that of the bulk dispersion. PMID- 22066790 TI - Randomized placebo- and active-controlled study of desvenlafaxine for menopausal vasomotor symptoms. AB - OBJECTIVE: To evaluate the efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) vs. tibolone and placebo for menopausal vasomotor symptoms and the incidence of uterine bleeding. METHODS: This 12-week, double blind, randomized, controlled trial was conducted at 35 sites in Europe, two sites in South Africa, and one site in Mexico. Postmenopausal women with >=50 moderate or severe hot flushes per week (n = 485) were randomized to desvenlafaxine 100 mg/day, tibolone 2.5 mg/day, or placebo. Reduction in the average daily number of moderate and severe hot flushes at weeks 4 and 12 (primary endpoint) was evaluated using analysis of covariance. Safety assessments included incidence of uterine bleeding, adverse events, laboratory values, and vital signs. RESULTS: At week 12, no statistically significant difference was observed in reduction of the average daily number of moderate and severe hot flushes for desvenlafaxine (-5.78) vs. placebo (-5.82; p = 0.921), although time to 50% reduction was significantly less than placebo (13 vs. 26 days, p = 0.006). Hot flush reduction with tibolone (-8.21) was significantly greater than placebo (p < 0.001). Nausea was the most common adverse event with desvenlafaxine, was generally mild to moderate, and resolved within the first 2 weeks. Significantly more subjects experienced bleeding with tibolone (23%) vs. desvenlafaxine (12%; p < 0.024) or placebo (9%; p < 0.001). CONCLUSIONS: Desvenlafaxine did not separate from placebo in reducing the number of moderate to severe hot flushes at week 12, although it did allow women to achieve 50% reduction sooner than placebo. Tibolone did separate from placebo, but with smaller than expected effect. The placebo effect was high (57%). Adverse drug reactions were consistent with the known safety profile of desvenlafaxine, and significantly more women who received tibolone experienced episodes of bleeding compared with women who received desvenlafaxine or placebo. PMID- 22066791 TI - Low-dose fish oil consumption prevents hepatic lipid accumulation in high cholesterol diet fed mice. AB - We examined the effects of low-dose fish oil ingestion on hepatic lipid accumulation caused after high cholesterol feeding in C57BL/6J mice. The mice were fed purified experimental diets consisting of 20 energy % (en%) safflower oil (SO or SO/CH), 2 en% fish oil + 18 en% safflower oil (2FO or 2FO/CH), or 5 en% fish oil + 15 en% safflower oil (5FO or 5FO/CH) with or without 2 weight % (wt %) cholesterol for 8 weeks. Hepatic triglyceride and total cholesterol contents were significantly lower in groups that were fed diets containing fish oil and cholesterol than in those that were fed safflower oil and cholesterol. The hepatic mRNA levels of fatty acid synthase (FAS) were lower in groups fed cholesterol or fish oil. Fatty acid oxidation-related hepatic gene expressions were higher in fish oil-fed groups. Fecal cholesterol excretion was higher in all cholesterol-fed groups; cholesterol excretion was high in groups fed fish oil and cholesterol. These results suggest that low-dose fish oil diets improve lipid metabolism by modifying the expression of lipid metabolism-related genes in the liver and increasing fecal cholesterol excretion. PMID- 22066792 TI - The development of the Tuebingen Cushing's disease quality of life inventory (Tuebingen CD-25). Part II: normative data from 1784 healthy people. AB - OBJECTIVE: In part I of the study, a health-related quality of life (HRQoL) inventory for Cushing's disease (CD), the Tuebingen Cushing-25 quality of life inventory (Tuebingen CD-25) was developed. In this second part, we aimed to assess normative data from healthy controls (HC) with which the individual patients' scores can be compared. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty-three patients with CD (52 women, 11 men) and 1784 HC (1210 women, 574 men) filled out the Tuebingen CD-25. MEASUREMENTS: HC received the inventory as a nondisease-specific quality of life questionnaire omitting the introductory sentence 'Because of my Cushing's disease' which was included in the CD group to be able to compare HRQoL in persons with and without CD. Slight and severe impairments were categorized according to the following principles: percent ranges >84.0% were classified as slight and percent ranges >95.0% as severe impairment. RESULTS: In 28.6% of our patients with CD, we found slight and in 41.3% severe impairment in the Total Score of the Tuebingen CD-25 compared with HC. Less than one-third of our patient sample presented with unimpaired HRQoL. In the patient population, impairment was found in all scales of the Tuebingen CD-25 to a similar extent (P = 0.444), pointing to the fact that all HRQoL domains are similarly impaired. We observed that female patients perceived a worse HRQoL than men in the domains depressive symptoms and social environment (P < 0.05). CONCLUSION: The Tuebingen CD-25 is a feasible instrument to assess HRQoL in CD in a clinical and investigative setting and provides normative data for all age groups and genders. PMID- 22066793 TI - Outcomes of liver transplantation for glycogen storage disease: a matched-control study and a review of literature. AB - BACKGROUND: The clinical characteristics and outcomes of patients with glycogen storage disease (GSD) who undergo liver transplantation (LT) have not been well defined. In this study, our objective was to determine the outcome of LT in patients with GSD and compare it with a comparable group of patients without GSD (matched controls). METHODS: UNOS data from 1986 to 2007 were used for this study. For each GSD patient (n = 95; men 62%) who was transplanted, three patients (n = 285, men 60%) without GSD (case controls) matched for age +/- five yr, year of transplantation and donor risk index (DRI) +/- 0.2 were identified from the UNOS database in a random manner. Unadjusted patient survival was determined by Kaplan-Meier survival analysis and significance determined by log rank test. RESULTS: The mean age of the group was 17.9 yr. GSD patients had lower BMI (22 vs. 24, p = 0.002), lower serum bilirubin (2.7 vs. 13.5 mg/dL, p < 0.0001), higher serum albumin (3.7 vs. 3.1 g/dL, p < 0.0001), and higher wait list time (239 vs. 74 d, p < 0.0001) compared to case controls. Recipient age and DRI were similar between the groups. Tumors were more common in GSD group (13.7% vs. 5%). Patient survival was significantly better (p = 0.024) in GSD group at one, five, and 10 yr (82%, 76%, and 64%) than non-GSD (73%, 65%, and 59%) group. CONCLUSIONS: In this matched-control study, patients who underwent LT for GSD had a better long-term survival than a comparable group of patients without GSD. PMID- 22066794 TI - Transit time affects the community stability of Lactobacillus and Bifidobacterium species in an in vitro model of human colonic microbiotia. AB - Retention time, which is analogous to transit time, is an index for bacterial stability in the intestine. Its consideration is of particular importance to optimize the delivery of probiotic bacteria in order to improve treatment efficacy. This study aims to investigate the effect of retention time on Lactobacilli and Bifidobacteria stability using an established in vitro human colon model. Three retention times were used: 72, 96, and 144 h. The effect of retention time on cell viability of different bacterial populations was analyzed with bacterial plate counts and PCR. The proportions of intestinal Bifidobacteria, Lactobacilli, Enterococci, Staphylococci and Clostridia populations, analyzed by plate counts, were found to be the same as that in human colonic microbiota. Retention time in the human colon affected the stability of Lactobacilli and Bifidobacteria communities, with maximum stability observed at 144 h. Therefore, retention time is an important parameter that influences bacterial stability in the colonic microbiota. Future clinical studies on probiotic bacteria formulations should take into consideration gastrointestinal transit parameters to improve treatment efficacy. PMID- 22066795 TI - Construction of a potentiometric glutamate biosensor for determination of glutamate in some real samples. AB - The potentiometric glutamate biosensor based on ammonium-selective poly(vinylchloride) (PVC) membrane electrode was constructed by chemically immobilizing glutamate oxidase. Ammonium ions produced after an enzymatic reaction were determined potentiometrically. We determined the optimum working conditions of the biosensor such as buffer concentration, buffer pH, lifetime, response time, linear working range, kinetic constants (K(m) and V(max)) of glutamate oxidase enzyme used for biosensor construction values, and other response characteristics. Additionally, glutamate assay in some real samples such as chicken bullion, healthy human serum, and commercial multipower amino acid mixture were also successfully carried out. The results showed good agreement with previously reported values. PMID- 22066796 TI - Polymerized human placenta hemoglobin given before ischemia protects rat heart from ischemia reperfusion injury. AB - This study was to investigate whether polymerized human placenta hemoglobin (PolyPHb) given before ischemia protects in vivo rat heart function against ischemia/reperfusion (I/R) injury. Forty-five male Sprague-Dawley rats were randomly divided (n = 15 per group) into a sham group, control group (pretreatment with Lactated Ringer's solution), or PolyPHb group (pretreatment with 0.1 gHb/kg PolyPHb). Rat hearts were subjected to 30-min ischemia by occlusion of left anterior descending, followed by 2-hr reperfusion. As compared to the control group, PolyPHb preserved cardiac function and reduced cardiac troponin-I release and histopathological changes. Therefore, PolyPHb pretreatment provided a profound cardioprotective effect on the in vivo rat heart. PMID- 22066797 TI - Immune safety evaluation of polymerized porcine hemoglobin (pPolyHb): a potential red blood cell substitute. AB - Polymerized Porcine Hemoglobin (pPolyHb), a hemoglobin-based oxygen carrier (HBOC), was developed as a potential red blood substitute for clinical applications. Assessment of its effects on the immune system is an important component of the overall safety evaluation of HBOC. For this purpose, we assessed three inflammation indicators, including complement C3a, IL-6, and TNF-? in cultured cells and in a rat model when pPolyHb was incubated or administrated with the cells/animals. Our results suggested that the levels of these three indicators were not statistically changed upon pPolyHb stimulation, indicating that pPolyHb is not immunotoxic to cells and animals in this aspect. PMID- 22066798 TI - Molecular genetic and chemotaxonomic characterization of the terrestrial cyanobacterium Nostoc commune and its neighboring species. AB - The phylogeny of the terrestrial cyanobacterium Nostoc commune and its neighboring Nostoc species was studied using molecular genetic and chemotaxonomic approaches. At least eight genotypes of N. commune were characterized by the differences among 16S rRNA gene sequences and the petH gene encoding ferredoxin NADP+ oxidoreductase and by random amplified polymorphic DNA analysis. The genotypes of N. commune were distributed in Japan without regional specificity. The nrtP gene encoding NrtP-type nitrate/nitrite permease was widely distributed in the genus Nostoc, suggesting that the occurrence of the nrtP gene can be one of the characteristic features that separate cyanobacteria into two groups. The wspA gene encoding a 36-kDa water stress protein was only found in N. commune and Nostoc verrucosum, suggesting that these Nostoc species that form massive colonies with extracellular polysaccharides can be exclusively characterized by the occurrence of the wspA gene. Fifteen species of Nostoc and Anabaena were investigated by comparing their carotenoid composition. Three groups with distinct patterns of carotenoids were related to the phylogenic tree constructed on the basis of 16S rRNA sequences. Nostoc commune and Nostoc punctiforme were clustered in one monophyletic group and characterized by the occurrence of nostoxanthin, canthaxanthin, and myxol glycosides. PMID- 22066799 TI - Supramolecular shuttle based on inclusion complex between cucurbit[6]uril and bispyridinium ethylene. AB - Cucurbit[6]uril (CB6) and bispyridinium ethylene form a stable inclusion complex. A rotaxane derived from this complex was prepared in which a CB6 wheel shuttles along an axle in an NMR time-resolved regime. PMID- 22066800 TI - Associations between technical quality of diabetes care and patient experience. AB - AIMS: It has long been held that high-quality care has both technical and interpersonal aspects. The nature and strength of any association between both aspects remain poorly explored. This study investigated the associations between diabetes patients' reports of receiving recommended care (as measures of technical quality) and their experience and ratings (as measures of interpersonal care). METHODS: Using data from a cross section of 3096 patients with diabetes nested within 24 diabetes-care-networks, we conducted multilevel regression analysis of the relationships between nine indicators of receiving care recommended in practice guidelines and: six scales of patient experience and global ratings of general practitioner, nurses, and overall diabetes care. RESULTS: On average, reporting having received recommended care was associated with reporting better patient experience and ratings. The extent and frequencies of these associations varied across the different care processes. Receiving foot examination, physical activity advice, smoking status check, eye examination, and HbA1c testing, but not nutritional advice, urine, cholesterol or blood pressure checks, were statistically associated with better patient experience and global ratings. Those who received HbA1c testing rated their overall care 1.002 points higher (95% confidence interval: 0.726-1.278) on a scale of 0-10 than those who did not. CONCLUSIONS: Higher self-reported technical quality of care in diabetes appears to be frequently but not always associated with better experiences and ratings. It is possible that the former leads to the latter and/or that both share a common cause within providers. Both care aspects do not seem interchangeable during performance assessment. PMID- 22066801 TI - Distribution patterns of mast cells in the uterus of pregnant Meishan pigs. AB - The present study was performed to investigate the numerical distribution of mast cells (MCs) in the uteri of pregnant Meishan pigs to explore the functions of MCs in pig pregnancy. The uterine samples from pregnant (on days 15, 26 and 50 of gestation) pigs were obtained respectively and stained with toluidine blue. The results were as follows: MCs were constitutively located in the uterus of the Meishan pig, with the distribution varying with gestational stages. On days 15 and 26 of gestation, MCs were mainly distributed around the blood vessels and uterine glands within the endometrium. On day 50 of gestation, MCs were mostly distributed in the myometrium. These results indicated that uterine MCs possibly have versatile functions in pig pregnancy. PMID- 22066803 TI - Reviews on animal diseases recently published in other journals. PMID- 22066802 TI - Interspecific hybridization increases MHC class II diversity in two sister species of newts. AB - Our understanding of the evolutionary mechanisms generating variation within the highly polymorphic major histocompatibility complex (MHC) genes remains incomplete. Assessing MHC variation across multiple populations, of recent and ancient divergence, may facilitate understanding of geographical and temporal aspects of variation. Here, we applied 454 sequencing to perform a large-scale, comprehensive analysis of MHC class II in the closely related, hybridizing newts, Lissotriton vulgaris (Lv) and Lissotriton montandoni (Lm). Our study revealed an extensive (299 alleles) geographically structured polymorphism. Populations at the southern margin of the Lv distribution, inhabited by old and distinct lineages (southern Lv), exhibited moderate MHC variation and strong population structure, indicating little gene flow or extensive local adaptation. Lissotriton vulgaris in central Europe and the northern Balkans (northern Lv) and almost all Lm populations had a high MHC variation. A much higher proportion of MHC alleles was shared between Lm and northern Lv than between Lm and southern Lv. Strikingly, the average pairwise F(ST) between northern Lv and Lm was significantly lower than between northern and southern Lv for MHC, but not for microsatellites. Thus, high MHC variation in Lm and northern Lv may result from gene flow between species. We hypothesize that the interspecific exchange of MHC genes may be facilitated by frequency-dependent selection. A marginally significant correlation between the MHC and microsatellite allelic richness indicates that demographic factors may have contributed to the present-day pattern of MHC variation, but unequivocal signatures of adaptive evolution in MHC class II sequences emphasize the role of selection on a longer timescale. PMID- 22066813 TI - Characterization of class I integrons among Salmonella enterica serovar Enteritidis isolated from humans and poultry. AB - A total of 84 Salmonella enterica serovar Enteritidis (S. Enteritidis) isolates, 42 of human and 42 of poultry origin, were characterized for antimicrobial resistance patterns and class I integrons. Among them, 58 (69%) S. Enteritidis were multidrug-resistant (MDR) and showed resistance to two or more antibiotic classes. By PCR assays and DNA sequencing, 50 (59.5%) S. Enteritidis isolates were found to carry class I integrons. Amplification of internal variable regions of class I integrons revealed five different arrays (0.75 kb only, 1 kb only, 1.3 kb only, both 1 and 1.2 kb, and both 1 and 1.3 kb). The integrons were further sequenced and the dfrA25 (0.75 kb), aadA1 (1 kb), aadA2 (1 kb), bla(PSE1) (1.2 kb) aadA6-orfD (1.3 kb) gene cassette arrays were identified. Ciprofloxacin minimum inhibitory concentration (MIC) values for the three isolates that showed resistance or reduced susceptibility via the disc diffusion method were 0.5-4 MUg mL(-1), although only three isolates exhibited resistance to cefteriaxone (MIC: 128-256 MUg mL(-1)) and four isolates were resistant to florfenicol (MIC: 32-128 MUg mL(-1)). In conclusion, the high rates of multidrug-resistance and class I integrons found among S. Enteritidis isolates in humans and poultry in Tehran suggest that efforts are needed to confine the prevalence of MDR Salmonella isolates. PMID- 22066814 TI - Late presenters, repeated testing, and missed opportunities in a Danish nationwide HIV cohort. AB - BACKGROUND: We aimed to estimate the incidence and predictors of late presentation among human immunodeficiency virus (HIV)-infected individuals in Denmark. METHODS: Incidence rates (IR) of presentation with advanced HIV (CD4 < 200 cells/MUl and/or acquired immune deficiency syndrome (AIDS)) and late presentation (CD4 < 350 cells/MUl and/or AIDS) were calculated per 100,000 population aged 16-60 y. Mortality rate ratios (MRR) were estimated using Poisson regression analysis. RESULTS: Three thousand and twenty-seven individuals were diagnosed with HIV in 1995-2009; 34.7% presented with advanced HIV and 51.2% were late presenters. The IR of HIV was stable (6.2/100,000 population), but IR of presentation with advanced HIV declined during the study period from 2.2 (95% confidence interval (CI) 1.8-2.8) to 1.1 (95% CI 0.8-1.5). Age >50 y, heterosexuals of non-Danish origin, 'other' route of transmission, and diagnosis before 2002 were associated with an increased risk of presenting with advanced HIV, whereas a negative HIV test prior to diagnosis was associated with a significantly reduced risk. A total of 414 individuals (40.0%) had attended a hospital 1-3 y before presenting with advanced HIV. After 2002 the proportion of men who have sex with men with a negative HIV test prior to diagnosis increased (incidence rate ratio (IRR) 1.3, 95% CI 1.1-1.6), coinciding with a reduction in IR of presentation with advanced HIV. Mortality rates were increased the first 2 y following presentation with advanced HIV (MRR 5.9, 95% CI 3.6-9.4 and MRR 2.5, 95% CI 1.4-4.1, respectively). CONCLUSION: In a setting with a low HIV prevalence, the rate of presentation with advanced HIV can potentially be reduced by repeated HIV testing of individuals with a continuous high risk of transmission and by adhering to guidelines for targeted HIV testing. PMID- 22066815 TI - Historical microbiology: revival and phylogenetic analysis of the luminous bacterial cultures of M. W. Beijerinck. AB - Luminous bacteria isolated by Martinus W. Beijerinck were sealed in glass ampoules in 1924 and 1925 and stored under the names Photobacterium phosphoreum and 'Photobacterium splendidum'. To determine if the stored cultures were viable and to assess their evolutionary relationship with currently recognized bacteria, portions of the ampoule contents were inoculated into culture medium. Growth and luminescence were evident after 13 days of incubation, indicating the presence of viable cells after more than 80 years of storage. The Beijerinck strains are apparently the oldest bacterial cultures to be revived from storage. Multi-locus sequence analysis, based on the 16S rRNA, gapA, gyrB, pyrH, recA, luxA, and luxB genes, revealed that the Beijerinck strains are distant from the type strains of P. phosphoreum, ATCC 11040(T), and Vibrio splendidus, ATCC 33125(T), and instead form an evolutionarily distinct clade of Vibrio. Newly isolated strains from coastal seawater in Norway, France, Uruguay, Mexico, and Japan grouped with the Beijerinck strains, indicating a global distribution for this new clade, designated as the beijerinckii clade. Strains of the beijerinckii clade exhibited little sequence variation for the seven genes and approximately 6300 nucleotides examined despite the geographic distances and the more than 80 years separating their isolation. Gram-negative bacteria therefore can survive for many decades in liquid storage, and in nature, they do not necessarily diverge rapidly over time. PMID- 22066816 TI - Emotional and behavioural reactions to tremors of the Umbria-Marche earthquake. AB - This is a study of 100 citizens of Fabriano, Italy, who experienced an earthquake. Results of a structured interview provide information on their emotional and behavioural reactions during and immediately after the earthquake as well as descriptions of the context. Respondents identify their coping responses during the earthquake as taking flight, freezing, taking shelter, failing to realize what was happening, reaching and protecting significant others, seeking information from the social environment, and recovering personal belongings. Moreover, in the aftermath of the earthquake, the most common responses were: evacuation, returning to houses, reuniting with family members, undertaking activities, observing the scene, recovering personal belongings, meeting in groups, and continuing activities. Respondents describe their emotional reactions as fear, helplessness, worry, and terror. Prosocial behaviour was frequent and looting did not occur. Emotional and cognitive reactions were influenced by environmental and social factors. PMID- 22066817 TI - Fast track echo of abdominal aortic aneurysm using a real pocket-ultrasound device at bedside. AB - BACKGROUND: Ultraminiaturization of echographic systems extraordinarily provides the image "within" the clinical examination. Abdominal aorta aneurysm (AAA) diagnosis based on conventional evaluation with a dedicated operator and ultrasound machine is still controversial due to the lack of evidence of the proposed management and guidelines' cost-effectiveness. We hypothesized that less expensive ultraportable devices could identify AAA with the same level of accuracy as conventional approaches. METHODS: A first step of this study was to validate the VSCAN's image capabilities in patients referred to the vascular Doppler laboratory. Abdominal aorta measurements were performed by an experienced physician using conventional equipment followed by a second blinded physician using the ultraportable device VSCAN. Then, 204 patients hospitalized in our cardiology institute were prospectively included for a systematic screening of AAA at bedside using the VSCAN in order to determine the feasibility and impact of fast track evaluation compared to clinical examination. RESULTS: A strong correlation was obtained between measurements of abdominal aorta diameters using the two ultrasound systems (r = 0.98, CI: 0.97-0.99, P < 0.001) with 100% of agreement for AAA diagnosis. In the second part of the study, visualization and measurement of the transverse diameter of the abdominal aorta was obtained in 199 patients, resulting in a feasibility of 97.5%. Among these patients, 18 AAAs were detected, which corresponds to a prevalence of 9%, whereas clinical evaluation did not detect any of them. Patients with AAA were more likely men (77.77% vs. 57.45%, P < 0.05) and hypertensive (88.8% vs. 56.9%, P < 0.05) as compared to those without AAA. Two patients with large AAA were quickly referred to the surgery department. CONCLUSION: Considering its low cost, diagnostic accuracy, and widespread availability, screening for AAA using an ultraportable ultrasound device such as VSCAN by an experienced physician is promising and should be used as an extension of routine physical examination in vascular patients. PMID- 22066818 TI - Mesogenic and luminescent properties of lyotropic liquid crystals containing Eu(III) and Tb(III) ions. AB - Lyotropic metallomesogens containing trivalent rare-earth metal ions have unique attractive behavior due to the combination of some specific properties of the lanthanide ions with anisotropic supramolecular organization liquid crystal and provide new promises in biochemistry and materials science. In this article, we have studied the liquid crystal and luminescence properties of lyotropic systems containing Eu(III) and Tb(III) ions based on nonionic surfactants. The type, the structural parameters of the mesophases, and the structure of a liquid crystal complex have been investigated using polarized optical microscopy (POM), X-ray diffraction, and Fourier transform infrared. In addition, on the basis of the luminescence lifetime, the structure of the first coordination sphere was determined. The results obtained based on time-resolved spectroscopy data are discussed in the light of the influence ligand environment, ion type, and the type of supramolecular organization on the luminescence efficiency of lyotropic lanthanide containing systems. The first time was reported for Eu(III) complexes increasing the luminescence efficiency in the hexagonal phase compared to the lamellar mesophase. PMID- 22066819 TI - Dark chocolate inhibits platelet isoprostanes via NOX2 down-regulation in smokers. AB - BACKGROUND: Dark chocolate is reported to decrease platelet activation but the underlying mechanism is still undefined. Dark chocolate is rich in polyphenols that could exert an antiplatelet action via inhibition of oxidative stress. The aim of the present study was to assess if dark chocolate inhibits platelet reactive oxidant species (ROS) formation and platelet activation. METHODS: Twenty healthy subjects (HS) and 20 smokers were randomly allocated to receive 40 g of dark (cocoa > 85%) or milk chocolate (cocoa < 35%) in a cross-over, single-blind study. There was an interval of 7 days between the two phases of the study. At baseline and 2 h after chocolate ingestion, platelet recruitment (PR), platelet ROS, platelet isoprostane 8-ISO-prostaglandin F2alpha (8-iso-PGF2alpha), Thromboxane (TxA2) and platelet activation of NOX2, the catalytic sub-unit of NADPH oxidase, and serum epicatechin were measured. RESULTS: Compared with HS, smokers showed enhanced PR, platelet formation of ROS and eicosanoids and NOX2 activation. After dark chocolate, platelet ROS (-48%, P < 0.001), 8-iso-PGF2alpha (-10%, P < 0.001) and NOX2 activation (-22%, P < 0.001) significantly decreased; dark chocolate did not affect platelet variables in HS. No effect of milk chocolate was detected in both groups. Serum epicatechin increased after dark chocolate in HS (from 0.454 +/- 0.3 nm to 118.3 +/- 53.7 nm) and smokers (from 0.5 +/- 0.28 nm to 120.9 +/- 54.2 nm). Platelet incubation with 0.1-10 MUm catechin significantly reduced PR, platelet 8-iso-PGF2alpha and ROS formation and NOX2 activation only in platelets from smokers. CONCLUSIONS: Dark chocolate inhibits platelet function by lowering oxidative stress only in smokers; this effect seems to be dependent on its polyphenolic content. PMID- 22066820 TI - Drug safety evaluation of intravitreal triamcinolone acetonide. AB - INTRODUCTION: Triamcinolone acetonide (TA) is a steroidal drug that has been widely administered intravitreally for retinal and choroidal conditions. Safety of steroidal products for intraocular use is essential because of their risk of ocular adverse events. This review comprehensively discusses the safety of intravitreal administration of TA. AREAS COVERED: This paper analyzes the mechanisms of action and key pharmacokinetic attributes and provides a discussion of the main clinical trials investigating clinical applications of intravitreal TA. The safety of intravitreal TA is evaluated through a search of the Medline database from 1980 to 2011. The most relevant literature on the safety of intravitreal TA is also discussed. EXPERT OPINION: The complications of intravitreal TA therapy include secondary ocular hypertension in about 20 - 40% of eyes, steroid-induced cataract in about 15 - 20% of cases and postinjection infectious endophthalmitis and pseudoendophthalmitis in less than 1%. TA is an effective drug for various retinal and choroidal diseases when delivered intravitreally. It may imply an off-label use and it may be associated with ocular adverse events. Intravitreal TA is not associated with significant systemic safety risks. PMID- 22066821 TI - Reactions at interfaces: oxygenation of n-butyl ligands anchored on silica surfaces with methyl(trifluoromethyl)dioxirane. AB - The oxygenation of n-butyl and n-butoxy chains bonded to silica with methyl(trifluoromethyl)dioxirane (1) revealed the ability of the silica matrix to release electron density toward the reacting C(2)-H sigma-bond through the Si C(1) and Si-O(1) sigma-bonds connecting the alkyl chain to the surface (silicon beta-effect). The silica surface impedes neither the alkyl chain adopting the conformation required for the silicon beta-effect nor dioxirane 1 approaching the reactive C(2) methylene group. Reaction regioselectivity is insensitive to changes in the solvation of the reacting system, the location of organic ligands on the silica surface, and the H-bonding character of the silica surface. Reaction rates are faster for those organic ligands either within the silica pores or bonded to hydrophilic silica surfaces, which evidence the enhanced molecular dynamics of confined dioxirane 1 and the impact of surface phenomena on the reaction kinetics. The oxygenation of n-butyl and n-butoxy chains carrying trimethylsilyl, trimethoxysilyl, and tert-butyl groups with dioxirane 1 under homogeneous conditions confirms the electronic effects of the silyl substituents and the consequences of steric hindrance on the reaction rate and regioselectivity. Orthosilicic acid esters react preferentially at the methylene group adjacent to the oxygen atom in clear contrast with the reactivity of the carboxylic or sulfonic acid alkyl esters, which efficiently protect this position toward oxidation with 1. PMID- 22066822 TI - Organization of water and atmospherically relevant ions and solutes: vibrational sum frequency spectroscopy at the vapor/liquid and liquid/solid interfaces. AB - The nature of water's hydrogen-bonding network is a vital influence on the chemistry that occurs at interfaces, but a complete understanding of interfacial water has proven elusive. Even-order nonlinear optical spectroscopies, such as vibrational sum frequency generation (VSFG) spectroscopy and heterodyne detected phase-sensitive sum frequency generation (PS-SFG) spectroscopy, are inherently surface specific. With the advent of advances in these spectroscopic techniques, researchers can now explore many long-standing questions about the dynamics and structures present at the vapor-water and water-solid interfaces. Of special interest to the atmospheric chemistry community is the accommodation of ions and solutes by water's hydrogen-bonding network. A better understanding of how ions and solutes behave in hydrogen-bonded water has afforded a fresh perspective of aqueous aerosols, because the interactions involved therein drive phenomena such as the hydrolysis of atmospheric chemical species. In this Account, we present work from our laboratory focusing on applying VSFG and the recently developed PS SFG techniques to probe the perturbation of water's hydrogen-bonding network at the vapor-water interface by a variety of ions and solutes. We also present very recent results from our laboratory on the direct observation of the adsorption of ions at the water-CaF(2) interface. We begin by discussing the influence of ions and solutes on interfacial water structure. Results for halide salts and the acid analogs on interfacial water structure are shown to be quite different, as would be expected from differences in surface tension measurements that have been known for a long time. Also examined are systems with the largely polarizable molecular anions nitrate (NO(3)(-)), sulfate (SO(4)(2-)), carbonate (CO(3)(2-)), and bicarbonate (HCO(3)(-)).These systems feature more complicated influences on interfacial water structure than halide-containing solutions; however, our conventional VSFG results for both nitrate and sulfate solutions are in agreement with recent PS-SFG results and molecular dynamics simulations. We also discuss recent PS-SFG work on carbonate and bicarbonate systems in which the accommodation of the bicarbonate ion at the vapor-water interface is in stark contrast to the carbonate results. Perturbation of interfacial water by solutes is examined for solutions of dimethyl sulfoxide and methylsulfonic acid. PS-SFG results for these systems are striking: they illustrate the dramatic changes that interfacial water molecules undergo in the presence of solutes that are not observed with conventional VSFG. Finally, we discuss direct sulfate ion adsorption for the aqueous sodium sulfate-CaF(2) interface, with the goal of elucidating water behavior at this surface. PMID- 22066823 TI - One-pot synthesis of hybrid multifunctional silica nanoparticles with tunable coating by click chemistry in reverse w/o microemulsion. AB - Multifunctional hybrid silica nanoparticles with a fluorescent core and tunable organic or polymeric shell can easily be prepared by a sol-gel process followed by 1,3 dipolar cycloaddition (CuAAC) in the same reverse quaternary W/O microemulsion. Compared to a classical multistep process, this one-pot synthesis reduces greatly the number of purification steps and avoids aggregation phenomena. The confinement of reactants inside the micellar system gives rise to a noticeable increase of the CuAAC reaction rate. In addition, using simultaneously two different substrates for CuAAC on silica allows us to obtain directly multifunctional hybrid nanoparticles displaying a double grafting without any separation or purification steps except the final recovery by centrifugation, which opens the door to a tunable coating of the nanoparticles. Particularly, the hydrophilic-lipophilic balance of the coating can be adjusted by implementing the pertinent MPEG:dodecyl azide ratio. As an application, the great versatility of this strategy has been proved by the one-pot synthesis of fluorescent silica nanoparticles with a PEG coating and encapsulating silver clusters. PMID- 22066824 TI - Soy protein based supplementation supports metabolic effects of resistance training in previously untrained middle aged males. AB - OBJECTIVE: To determine changes in body composition, physical performance, metabolic and hormonal parameters induced by lifestyle counselling, resistance training and resistance training with soy protein based supplemention in middle aged males. DESIGN: Randomised controlled study consisting of resistance training without (RT-G) or with (RTS-G) a soy protein based supplement and a control group with lifestyle education only (LE-G). SUBJECTS: Forty healthy middle aged men (50 65 years, BMI 25-29.9 kg/m2). MEASUREMENTS: Changes in body weight (BW) and waist circumference (WC) were measured and body composition (BC), fat mass (FM), lean body mass (LBM) were measured by skin fold anthropometry at baseline and after 12 weeks of intervention. In addition, changes in physical fitness, metabolic and hormonal parameters (lipids, glucose, fructosamines, insulin, insulin-like growth factor-1, Leptin, human growth hormone, dehydroepiandrosterone, testosterone, hs CRP, Il-6) were evaluated. RESULTS: Thirty-five participants completed the 12 week study. No significant changes in BW were noted although RM and WC dropped and LBM increased after training, particularly in the RTS group (FM 22.6 +/- 5.5 kg to 21.2 +/- 4.7 kg; LBM 68.5 +/- 7.2 kg to 70.1 +/- 7.4; p < 0.01). Subjects in the RTS group experienced more pronounced improvements in the strength measurements than the RT group. After the training intervention there were significant changes in hormonal and metabolic parameters as well as in glycemic control, particularly in the RTS group. CONCLUSIONS: Our data suggest that resistance training, particularly in combination with a soy protein based supplement improves body composition and metabolic function in middle aged untrained and moderately overweight males. PMID- 22066825 TI - Universal tracer monitored titrations. AB - Titrations, while primarily known as the chemical rite of passage for fledgling science students, are still widely used for chemical analysis. With its many years of existence and improvement, the method would seem an unlikely candidate for innovation, yet it is desirable, in this age of autonomous sensing where analyzers may be sent into space or to the bottom of the ocean, to have a simplified titrimetric method that does not rely upon volumetric or gravimetric measurement of sample and titrant. In previous work on the measurement of seawater alkalinity, we found that use of a tracer in the titrant eliminates the need to measure mass or volume. Here, we show the versatility of the method for diverse types of titrations and tracers. The results suggest that tracers may be employed in all types of titrations, opening the door for greatly simplified laboratory and field-based chemical analysis. PMID- 22066826 TI - Cerebellar malformations alter regional cerebral development. AB - AIM: The aim of this study was to compare total and regional cerebral volumes in children with isolated cerebellar malformations (CBMs) with those in typically developing children, and to examine the extent to which cerebellar volumetric reductions are associated with total and regional cerebral volumes. METHOD: This is a case-control study of children diagnosed with isolated CBMs. Each child was matched on age and sex to two typically developing children. Using advanced three dimensional volumetric magnetic resonance imaging, the cerebrum was segmented into tissue classes and partitioned into eight regions. Analysis of variance was used to compare cerebral volumes between children with CBMs and control children, and linear regressions to examine the impact of cerebellar volume reduction on cerebral volumes. RESULTS: Magnetic resonance imaging was performed at a mean age of 27 months in 20 children (10 males, 10 females) with CBMs and 40 typically developing children. Children with CBMs showed significantly smaller deep grey matter nuclei (p < 0.001), subgenual white matter (p = 0.03), midtemporal white matter (p = 0.02), and inferior occipital grey matter (p = 0.03) volumes than typically developing children. Greater cerebellar volumetric reduction in children with CBMs was associated with decreased total cerebral volume and deep grey matter nuclei (p = 0.02), subgenual white/grey matter (p = 0.001), midtemporal white (p = 0.02) and grey matter (p = 0.01), and parieto-occipital grey matter (p = 0.004). INTERPRETATION: CBMs are associated with impaired regional cerebral growth, suggesting deactivation of principal cerebello-cerebral pathways. PMID- 22066827 TI - Efficacy of porcine placental extracts with hormone therapy for postmenopausal women with knee pain. AB - OBJECTIVES: Knee pain related to osteoarthritis increases with age and is more common in middle-aged women. Although hormone replacement therapy (HRT) improves knee pain, women unresponsive to HRT need an effective adjunctive therapy. The aim of this study was to assess whether oral porcine placental extracts (PPE) have an impact on patients with knee pain as an adjunctive therapy combined with HRT. METHODS: Forty-eight postmenopausal women with knee pain receiving HRT were enrolled into this open-label, randomized, controlled study. Subjects were randomized into Group 1 (n= 24) or Group 2 (n=24). Subjects in Group 1 were given 3 months open treatment with calcium (260 mg/day) as adjunctive therapy combined with HRT. Group 2 received PPE (9 capsules/day) as adjunctive therapy combined with HRT. Changes in the degree of knee pain were evaluated by the Visual Analog Scale (VAS). RESULTS: Treatment with PPE was significantly effective in reducing the VAS score for knee pain at 4 weeks (p < 0.05), at 8 weeks (p< 0.01) and at 12 weeks (p<0.01), compared with the control group. Interestingly, the effects continued for 4 weeks after cessation of treatment in the PPE group (p< 0.01) compared with the control group. The PPE treatment had no significant adverse effects on blood biochemical and metabolic profiles, especially related to the risk factors for cardiovascular disease. CONCLUSION: PPE is a possible option as an adjunctive oral supplement in the case of HRT-resistant, long-lasting knee pain. PMID- 22066828 TI - Emerging research supporting the positive effects of berries on human health and disease prevention. AB - The cluster of papers included here is taken from research presentations at the most recent Berry Health Benefits Symposium (BHBS). The BHBS is a biennial conference that was initiated in 2005 and met for the fourth time in 2011. Similar to the past three meetings, the 2011 BHBS covers emerging and adds to the growing body of scientific knowledge supporting the positive effects of berry fruit on human health promotion and disease prevention. Important aspects of the BHBS also include fostering open communication and collaboration among several disparate groups necessary to ensure regular and continued consumption of berry fruits among the population. These groups include berry growers, producers, and processors, as well as basic and clinical researchers, media representatives, and health professionals. Thus, the BHBS continues to be an excellent forum for presenting and disseminating new and ongoing berry health benefits research. PMID- 22066830 TI - Regiochemical substituent switching of spin states in aryl(trifluoromethyl)carbenes. AB - Although aryl(trifluoromethyl)diazirines have achieved great popularity in photoaffinity labeling applications, the properties of the corresponding carbenes have not been as widely explored. Here, low-temperature matrix-isolation spectroscopy and reactivity studies indicate that in contrast to m methoxyphenyl(trifluoromethyl)carbene and most known aryl(CF(3))carbenes, the para isomer is a ground-state singlet rather than triplet. DFT calculations support these results as well as the notion that the p-CH(3)O group stabilizes the singlet carbene via resonance. These results may have relevance to the wide range of substituted aryl(CF(3))diazirines in photoaffinity applications. PMID- 22066831 TI - Effects of L-ascorbic acid 2-phosphate magnesium salt on the properties of human gingival fibroblasts. AB - BACKGROUND AND OBJECTIVE: L-Ascorbic acid 2-phosphate magnesium salt (APM) is an L-ascorbic acid (AsA) derivative developed to improve AsA stability and display effective biochemical characteristics. This study aimed to investigate the effects of APM on the functions and properties of human gingival fibroblasts with respect to the prevention of periodontal disease in comparison with those of AsA. MATERIAL AND METHODS: Human gingival fibroblasts were incubated in the presence or absence of APM or L-ascorbic acid sodium salt (AsANa). Intracellular AsA was analysed by HPLC. Collagen synthesis was measured by ELISA and real-time RT-PCR. Intracellular reactive oxygen species (ROS) induced by hydrogen peroxide (H(2)O(2)) were quantified using a fluorescence reagent, and cell damage was estimated with calcein acetoxymethyl ester. Furthermore, intracellular ROS induced by tumor necrosis factor-alpha (TNF-alpha) were quantified, and expression of TNF-alpha-induced interleukin-8 expression, which increases due to inflammatory reactions, was measured by ELISA and real-time RT-PCR. RESULTS: APM remarkably and continuously enhanced intracellular AsA and promoted type 1 collagen synthesis and mRNA expression. Furthermore, APM decreased cell damage through the suppression of H(2)O(2)-induced intracellular ROS and inhibited interleukin-8 production through the suppression of TNF-alpha-induced intracellular ROS. These effects of APM were superior to those of AsANa. CONCLUSION: These results suggest that APM is more effective than AsANa in terms of intake, collagen synthesis, decreasing cell damage and inhibiting interleukin 8 expression in human gingival fibroblasts. This suggests that local application of APM can help to prevent periodontal disease. PMID- 22066832 TI - Recording of quality indicators in the management of acute coronary syndromes: predictors of reperfusion times. AB - BACKGROUND: There is wide variation in recording of reperfusion times in the management of ST segment elevation acute coronary syndromes (ACS). We investigated factors that could predict time to reperfusion. METHODS: Single centre, retrospective study of all consecutive patients admitted for primary PCI from June 2009 to October 2010. Door-to-artery (D2A) and Door-to-balloon (D2B) times were calculated from times noted by cathlab. nurses and compared with times from digital recordings of PCI procedures. Predictors of time to reperfusion were identified by logistic regression. RESULTS: 300 patients were included. Median (interquartile range) D2B time recorded by cathlab. nurses (D2B-CN) was 35.5 (24; 52) minutes, 32 (20; 51) min from PCI recordings (D2B-PCI). Average difference between D2B-CN and D2B-PCI was 6.2 min (P < 0.0001). Concordance of percent patients with a D2B time < 90 and < 45 min was mediocre, kappa coefficients 0.44 (95% CI: 0.10-0.79) and 0.68 (95% CI: 0.57-0.80) respectively. By multivariate analysis, older patients had longest D2A times (P = 0.04); patients with longest D2A and D2B times more frequently had elevated creatinine (P = 0.002 (D2A), P = 0.0003 (D2B). Organizational aspects did not influence reperfusion times. CONCLUSION: Data regarding reperfusion times are unreliable when recorded by nurses. Age and creatinine levels are significantly associated with reperfusion times, whereas organizational aspects are not. PMID- 22066833 TI - Bacterial communities associated with hydraulic fracturing fluids in thermogenic natural gas wells in North Central Texas, USA. AB - Hydraulic fracturing is used to increase the permeability of shale gas formations and involves pumping large volumes of fluids into these formations. A portion of the frac fluid remains in the formation after the fracturing process is complete, which could potentially contribute to deleterious microbially induced processes in natural gas wells. Here, we report on the geochemical and microbiological properties of frac and flowback waters from two newly drilled natural gas wells in the Barnett Shale in North Central Texas. Most probable number studies showed that biocide treatments did not kill all the bacteria in the fracturing fluids. Pyrosequencing-based 16S rRNA diversity analyses indicated that the microbial communities in the flowback waters were less diverse and completely distinct from the communities in frac waters. These differences in frac and flowback water communities appeared to reflect changes in the geochemistry of fracturing fluids that occurred during the frac process. The flowback communities also appeared well adapted to survive biocide treatments and the anoxic conditions and high temperatures encountered in the Barnett Shale. PMID- 22066834 TI - Echinopsacetylenes A and B, new thiophenes from Echinops transiliensis. AB - Two new polyacetylene thiophenes, echinopsacetylenes A and B (1 and 2), were isolated from the roots of Echinops transiliensis. The structures of 1 and 2 were elucidated on the basis of spectroscopic analyses and chemical transformations. Echinopsacetylenes A (1) is the first natural product possessing an alpha terthienyl moiety covalently linked with another thiophene moiety. Echinopsacetylenes B (2) is the first natural thiophene conjugated with a fatty acid moiety. Echinopsacetylene A (1) showed toxicity against the Formosoan subterranean termite (Coptotermes formosanus). PMID- 22066835 TI - Successful sirolimus rescue in tacrolimus-induced thrombotic microangiopathy after living-related liver transplantation. AB - TMA is a rare complication of tacrolimus. Disruption of endothelial cells, platelet aggregation, and intravascular mechanical fragmentation of red cells are core mechanisms of injury; however, exact pathways of toxicity are not clear. The clinical presentation may vary but TMA is a potentially life-threatening condition usually demanding aggressive treatment. We present the case of TMA in a child after living-related liver transplantation (LRLTx) on tacrolimus-based immunosuppressive regiment successfully converted to sirolimus. PMID- 22066837 TI - Bibliographic data, including abstracts and addresses of the authors. PMID- 22066836 TI - Effect of dilution temperature on boar semen quality. AB - As boar semen is very sensitive to cold shock and changes in temperature during semen processing can have a profound impact on semen quality, the effect of the extender temperature at the time of dilution was investigated in a two-step dilution protocol for boar semen being processed for liquid storage. Fifteen boars of different breeds and ages from a commercial artificial insemination centre were included. One ejaculate per boar was collected and processed with Beltsville Thawing Solution semen extender. Each ejaculate was diluted (1 : 1) at 30 degrees C, and subsequently, the samples were diluted (30 * 10(6) sperm/ml) with either preheated extender [29.3 degrees C +/- 0.2 degrees C, group A (GA)] or extender at room temperature [22.7 degrees C +/- 0.6 degrees C, group B (GB)]. Samples were transported to the Faculty of Veterinary Medicine (University of Ghent, Belgium) in two isotherm boxes (one per group), stored at 17 degrees C and investigated for three consecutive days (D0 to D2). At D0, D1 and D2, motility parameters [computer-assisted semen analysis (CASA)] and the per cent of sperm with intact membrane (% IM) by eosin nigrosin staining were evaluated. At D0 and D2, the % of sperm with intact acrosome (% IA) was studied by Pisum sativum agglutinin staining. The average temperature of the 1 : 1 dilution was 29.4 degrees C +/- 1.1 degrees C immediately after extender addition. No significant differences were found between groups for per cent motility [79.3 +/- 9.0 for GA and 81.1 +/- 9.2 for GB (p = 0.372)], % progressive motility [56.5 +/- 13.3 for GA and 58.4 +/- 13.8 for GB (p = 0.737)] or any CASA parameter. No differences were found for % IM [85.1 +/- 10.7 and 84.5 +/- 3.8 for GA and GB, respectively (p = 0.761)] and % IA [72.2 +/- 9.4 for GA and 68.3 +/- 16.6 for GB (p = 0.792)]. In conclusion, when a two-step dilution is performed, preheating the extender for the second dilution to match the semen temperature did not result in better semen quality compared to a dilution at a moderate room temperature. PMID- 22066839 TI - The genetic basis of evolution, adaptation and speciation. AB - A primary question in biology concerns the genetic basis of the evolution of novel traits, often in response to environmental changes, and how this can subsequently cause species isolation. This topic was the focus of the symposium on the Genetics of Speciation and Evolution at the annual meeting of the Canadian Society for Ecology and Evolution, held in Banff in May 2011. The presentations revealed some of the rapid advances being made in understanding the genetic basis of adaptation and speciation, as well as the elegant interplay between an organism's genetic complement and the environment that organism experiences. PMID- 22066850 TI - Two-dimensional antigenic dendrogram and phylogenetic tree of avian influenza virus H5N1. AB - The hemagglutination-inhibition (HI) titers of a panel of 25 mouse monoclonal antibodies (MAbs) against 44 isolates of highly pathogenic avian influenza virus H5N1 were determined. A two-dimensional antigenic dendrogram was constructed by hierarchical clustering of HI titers. Viruses with similar reactivity patterns were clustered horizontally, whereas MAbs were clustered vertically. In this 2-D dendrogram, with 40% similarity as a cut-off, four virus clusters and four MAbs clusters were identified. A phylogenetic tree based on the deduced amino acid sequence of the hemagglutinin gene of tested viruses was constructed and its topology was compared to the antigenic dendrogram. Interestingly, viruses with high genetic homology in the phylogenetic tree also had high similarity in their reactivity patterns, as indicated by their relatedness in the tree and close clustering in the dendrogram, respectively. However, the reverse and the converse were also true. Of the five pairs of viruses in the dendrogram with bootstrap values higher than 75, four pairs were in concordance with their genetic relatedness. However, one pair contained viruses belong to two distinct genetic clades. These results were discussed in the context of antigenic variation, genetic polymorphism, and the potential application of MAbs in antigenic analysis. PMID- 22066851 TI - Kinetics of hepatitis C virus load and hemodialysis: is there any influence of the reuse of dialysis membrane on HCV viremia? AB - BACKGROUND: Patients with chronic kidney disease (CKD) on regular hemodialysis are at increased risk of acquiring hepatitis C virus (HCV). Although controversial, a distinct dynamic of the HCV load has been reported in this group - a lower HCV viremia compared to non-uremic patients. The reasons for this remain unclear, but the host immune response related to the hemodialysis procedure and the reuse of dialysis membranes are the most investigated factors. METHODS: We analyzed the kinetics of HCV RNA viremia in 21 hemodialysis patients infected with genotype 1, through a highly sensitive quantitative method (real time polymerase chain reaction), immediately before and at the end of the first use and the last reuse of the cellulose diacetate dialysis membrane. RESULTS: Initial HCV load did not correlate with demographic or biochemical parameters, but higher HCV viremia was associated with a longer time on hemodialysis (r = 0.44, p = 0.04). Although not significant, HCV RNA decreased in 11/21 (52.3%) patients after the first dialysis session (median 279,000 vs 176,000 IU/ml, p = 0.91). However, a significant increase in HCV RNA viremia was observed in 17/21 (80.9%) patients after the tenth session (median 187,000 vs 342,000 IU/ml, p = 0.009). CONCLUSIONS: Except for the first session of hemodialysis, we did not confirm a decrease in HCV viremia related to the time on hemodialysis or with the reuse of the dialysis membrane. Factors other than the reuse of the dialysis membrane might be involved in the multifaceted kinetics of HCV RNA in CKD patients on hemodialysis. PMID- 22066852 TI - Biodiversity, abundance, and activity of nitrogen-fixing bacteria during primary succession on a copper mine tailings. AB - Microorganisms are important in soil development, inputs and biogeochemical cycling of nutrients and organic matter during early stages of ecosystem development, but little is known about their diversity, distribution, and function in relation to the chemical and physical changes associated with the progress of succession. In this study, we characterized the community structure and activity of nitrogen-fixing microbes during primary succession on a copper tailings. Terminal fragment length polymorphism (T-RFLP) and clone sequencing of nifH genes indicated that different N(2) -fixing communities developed under primary succession. Phylogenetic analysis revealed a diversity of nifH sequences that were mostly novel, and many of these could be assigned to the taxonomic divisions Proteobacteria, Cyanobacteria, and Firmicutes. Members of the Cyanobacteria, mostly affiliated with Nostocales or not closely related to any known organisms, were detected exclusively in the biological soil crusts and represented a substantial fraction of the respective diazotrophic communities. Quantitative PCR (and statistical analyses) revealed that, overall, copy number of nifH sequences increased with progressing succession and correlated with changes in physiochemical properties (including elementary elements such as carbon and nitrogen) and the recorded nitrogenase activities of the tailings. Our study provides an initial insight into the biodiversity and community structure evolution of N(2) -fixing microorganisms in ecological succession of mine tailings. PMID- 22066853 TI - Long-term gendered consequences of permanent disabilities caused by the 2005 Pakistan earthquake. AB - This study documents the long-term gendered impact of the 2005 Pakistan earthquake on women and men who were rendered paraplegic as a result of spinal cord injuries sustained during the disaster. Coping mechanisms are also mapped. The findings show that three years after the disaster, paraplegic women are socially, emotionally, and financially isolated. The small stipend they receive is a significant source of income, but it has also led to marital distrust, violence, and abuse. In contrast, men receive full social and emotional support. Their key concern is that the government is not providing them with opportunities to be economically productive. Contemporary discourse and post-disaster policies, while acknowledging the importance of incorporating a gender perspective in the immediate post-disaster period, have failed to acknowledge and address the longer term gendered impact of disasters, in terms of the different types of impact and strategies adopted by women and men. PMID- 22066854 TI - Which factors impact myocardial function in systemic sclerosis? AB - BACKGROUND: The aim of our study was to determine clinical and echocardiographic parameters, which impacted the left (LV) and right ventricular (RV) diastolic and global function in patients with systemic sclerosis (SSc). METHODS: The study included 50 SSc patients and 48 age-matched healthy volunteers. All the patients underwent clinical examination, serological tests, pulmonary function testing, and complete two-dimensional echocardiography, which included pulsed and tissue Doppler. We determined the ratio of early diastolic transtricuspid/transmitral and the lateral area of the tricuspid/mitral annulus flow velocities (E/e';(lateral) ). RV and LV global ventricular function was estimated by the Tei index. Pulmonary vascular resistance (PVR) was calculated by using echocardiographic parameters. RESULTS: Tricuspid inflow E/A ratio was decreased in the SSc group (P < 0.001), also as e'/a' ratio (P < 0.001), whereas E/e'(tricuspid) was increased (P = 0.001). The RV Tei index was increased in SSc patients (P < 0.001). PVR was significantly higher than in controls (P < 0.001). The multivariate analysis showed that brain natriuretic peptide (BNP) level (beta= 0.403, P = 0.016), diffusion capacity for carbon monoxide (DLCO; beta= 0.361, P = 0.025), RV systolic pressure (beta= 0.449, P = 0.011), and PVR (beta= 0.507, P < 0.001) were independently associated with RV diastolic function (tricuspid E/e'(lateral) ). Similar results were achieved for the RV Tei index. Multiple regression showed that BNP level (beta= 0.337, P = 0.029), DLCO (beta= 0.405, P = 0.011), and PVR (beta= 0.449, P = 0.022) were independently associated with LV diastolic function (mitral E/e'(lateral) ). Similar results were obtained for the LV Tei index. CONCLUSION: Our study revealed some new noninvasive parameters (BNP, DLCO, and PVR), which are useful for everyday clinical practice for determining of early myocardial involvement in SSc. (Echocardiography, ****;**:1-11). PMID- 22066855 TI - The clinical safety of lenalidomide in multiple myeloma and myelodysplastic syndromes. AB - INTRODUCTION: Lenalidomide is an IMiDs(r) oral immunomodulatory compound developed for the treatment of patients with multiple myeloma (MM) and myelodysplastic syndromes (MDS). Long-term continuous treatment with lenalidomide beyond first response may be important to optimize responses and delay relapse. AREAS COVERED: This review summarizes the lenalidomide mechanism of action, pharmacodynamics, key clinical studies with a focus on safety and post-marketing surveillance data. The necessity for early adverse-event management, including dose modifications for neutropenia and thrombocytopenia, and venous thromboembolism prophylaxis, where applicable, in order to maintain patients on treatment and achieve optimal efficacy, is discussed. Secondary primary malignancies in MM and progression to acute myeloid leukemia in MDS patients in the context of lenalidomide treatment are also discussed. Finally, as lenalidomide is renally excreted, the requirement for dose adjustment according to creatinine clearance is discussed. EXPERT OPINION: Lenalidomide is highly effective and generally well tolerated. Most adverse events occur early during the course of treatment and are manageable. Lenalidomide is not associated with peripheral neuropathy and has a lack of cumulative toxicity, making it an effective treatment option for long-term use in the management of MM and low/intermediate-1-risk MDS, specifically with chromosome 5q deletion with or without other cytogenetic abnormalities. PMID- 22066856 TI - Detection of vertical root fractures in non-endodontically treated molars using cone-beam computed tomography: a report of four representative cases. AB - Vertical root fractures (VRFs) in teeth without endodontic treatment are relatively uncommon. The diagnosis is based on clinical and radiographic presentations. It might be difficult to detect VRFs in non-endodontically treated molars by conventional radiographs in certain situations because of the limitations of 2D images and many others factors such as the VRFs being in their early stages. Root morphology variation and the orientation of VRFs can influence conventional radiographic detection and the interpretation of a radiolucent fracture line. The four case reports presented here describe and discuss the use of cone-beam computed tomography (CBCT) in successfully diagnosing VRFs based on direct visualization of radiolucent lines, especially those suspected from routine conventional radiographs, as well as their symptoms and clinical findings. CBCT also provides more information on the presence of VRFs. PMID- 22066857 TI - Preparation of a family of 10-hydroxybenzo[h]quinoline analogues via a modified Sanford reaction and their excited state intramolecular proton transfer properties. AB - We have developed a highly optimized methodology that allows for the oxidative acetoxylation of a sterically and electronically demanding library of analogues of benzo[h]quinoline. The optimal conditions for the insertion of an OAc group were identified after examining various reaction parameters (solvent, oxidant, catalyst, temperature, time). The conditions identified (Pd(OAc)(2), PhI(OAc)(2), MeCN, 150 degrees C, 16 h), combined with the hydrolysis of acetates, resulted in the formation of hydroxybenzoquinolines in 27-59% yield, whereas all previously published procedures were ineffective. This synthesis was compatible with diverse functionalities (ester, aldehyde, carbon-carbon triple bond) and, most importantly, worked for sterically hindered analogues as well as for compounds possessing electron-donating and electron-withdrawing substituents at various positions. All the obtained compounds demonstrated excited-state intramolecular proton transfer (ESIPT) manifesting as small fluorescence quantum yields and large Stokes shifts (8300-9660 cm(-1)). The effect of structural variations in eight 10-hydroxybenzo[h]quinoline analogues on absorption and emission properties was studied in detail. PMID- 22066858 TI - Nanomolar hydrogen peroxide detection using horseradish peroxidase covalently linked to undoped nanocrystalline diamond surfaces. AB - In this article, we report on the low-level detection of hydrogen peroxide, a key player in the redox signaling pathway and a toxic product in the cellular system, using a colorimetric solution assay. Amine-terminated undoped nanocrystalline diamond thin films were grown on glass using a linear-antenna microwave plasma CVD process. The diamond surface consists mainly of -NH(2) termination. The aminated diamond surface was decorated with horseradish peroxidase (HRP) enzyme using carbodiimide coupling chemistry. The success of the HRP immobilization was confirmed by X-ray photoelectron spectroscopy (XPS). The enzymatic activity of immobilized HRP was determined with a colorimetric test based on the HRP catalyzed oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sufonic acid (ABTS) in the presence of hydrogen peroxide. The surface coverage of active HRP was estimated to be Gamma = 7.3 * 10(13) molecules cm(-2). The use of the functionalized diamond surface as an optical sensor for the detection of hydrogen peroxide with a detection limit of 35 nM was demonstrated. PMID- 22066859 TI - Social, cultural and political factors in the design of HIV programmes with Papuan highland communities. AB - The Indonesian province of Papua faces a growing HIV epidemic, particularly amongst remote highland Papuans, such as the Western Dani. The specific, challenging political and sociocultural context of Papuan highland communities greatly influences the transmission of HIV. Different initiatives have struggled to meet the sexual and reproductive health needs of Papuan communities and of minority ethnic communities and the challenges they pose. The prolonged cultural tensions between Papuan and Indonesian communities are a major barrier to effective dialogue between the Indonesian state and its minority ethnic communities, the absence of which only exacerbates the epidemic. Tackling HIV in Papua requires responses that are both culturally and politically sensitive, in direct challenge to existing development paradigms. PMID- 22066860 TI - Total synthesis and structural revision of the piperarborenines via sequential cyclobutane C-H arylation. AB - A strategy for the construction of unsymmetrical cyclobutanes using C-H functionalization logic is demonstrated in the total synthesis of piperarborenine B and piperarborenine D (reported structure). These syntheses feature a new preparation of cis-cyclobutane dicarboxylates from commercially available coumalate starting materials and a divergent approach to the controlled cis or trans installation of the two distinct aryl rings found in the natural products using the first example of cyclobutane C-H arylation. The structure of piperarborenine D is reassigned to a head-to-head dimer, which was synthesized using an intramolecular [2+2] photocycloaddition strategy. PMID- 22066861 TI - A comparative study of the sonographic appearance and anatomy of the obturator internus in normal males. AB - The aim of this study was to compare the appearance of the normal male obturator internus on transrectal ultrasound with anatomical examination to advance the knowledge of the male pelvic muscles. This information may help to provide a new imaging method for observation of the normal male obturator internus and may facilitate the treatment of obturator internus abscesses and various other types of interventional therapies. Ten formalin-fixed male cadavers were dissected to examine the appearance and structure of the obturator internus and its relationship with the structures in close proximity. The obturator internus was also observed in five fresh male cadavers using transrectal ultrasound, after which the anatomy of the muscle was confirmed by dissection and its thickness measured. The visible fusiform was observed by sonography. The measurements of obturator internus thickness were 13.33 +/- 0.32 mm on the right and 13.41 +/- 0.26 mm on the left; in the formalin-fixed fresh cadaver, the measurements were 13.16 +/- 0.21 mm on the right and 13.17 +/- 0.22 mm on the left. Using transrectal ultrasound to recognize and observe the obturator internus is a new imaging method that will provide a foundation for the recognition of its abnormalities in the future. PMID- 22066862 TI - Ergonomics of and technologies for single-port lapaxroscopic surgery. AB - BACKGROUND: There are a number of major constraints in ergonomics of and technologies for single port laparoscopic surgery. MATERIAL AND METHODS: The review is based on a complete literature search through PubMed, Medline. Single port laparoscopic surgery (SPLS), single incision laparoscopic surgery (SILS), laparoscopic single-site surgery (LESS), ergonomics, technologies, robotic SPLS, SPLS or SILS operations were the keywords used for the literature search. RESULTS AND DISCUSSION: The SPLS approach imposes several restrictions: Maintenance of sufficient exposure, sustained pneumoperitoneum, adequate retraction, collision between instruments (internal and external), collision between instruments and optics, and limited instrument manipulation and triangulation. Compensatory techniques such as using percutaneous sutures for retraction and employing coaxial, flexible, and articulating instruments have been used to improve triangulation. CONCLUSIONS: The ergonomics imposed by this approach are different from those of multi-port laparoscopic surgery. Considerable progress in port and instruments for SPLS has been achieved in the last five years in order to overcome the constraints and problems facing the operating surgeon when using the SPLS approach. Further more advanced instrumentation such as hand-held manipulators with seven degrees of freedom (DOF) and robotic devices for SPLS is needed to realize the full potential of the SPLS approach. PMID- 22066863 TI - Low bone mineral density in Indian patients with fragility fractures. AB - OBJECTIVE: Low bone mineral density (BMD) is a major risk factor for fragility fractures in osteoporosis. In recent studies, its use with clinical risk factors has been shown to enhance prediction of fragility fractures. The present study was done to assess BMD in Indian patients with fragility fractures using digital X-ray radiogrammetry (DXR-BMD). METHODS: A total of 228 patients (64 male and 164 female) admitted to an Orthopedic Hospital for management of fragility fracture were recruited. For each patient, DXR-BMD was obtained from an anteroposterior radiograph of the non-dominant hand. RESULTS: The number of subjects with hip fracture was 104 (40 male, 64 female). Vertebral fractures were seen in 67 patients (11 male, 56 female) and distal radial fracture in 57 patients (13 male, 44 female). The DXR-BMD (g/cm(2)) was significantly lower in subjects with any fragility fracture (0.51 vs. 0.58 in men and 0.41 vs. 0.54 in women). When compared to the age-matched normative reference data by decade, all subjects with fragility fracture had significantly lower DXR-BMD except male subjects in the age decade of 40-49 years. CONCLUSION: This study confirms lower DXR-BMD in Indian subjects with fragility fractures. This may have a potential role in fracture prediction when used with clinical risk factors in the Indian population. PMID- 22066864 TI - Impact of vitamin D-related serum PTH reference values on the diagnosis of mild primary hyperparathyroidism, using bivariate calcium/PTH reference regions. AB - BACKGROUND, OBJECTIVE: An international consensus conference underlined the importance of defining upper parathyroid hormone (PTH) reference values based on 25-OH-vitamin D [25(OH)D] to diagnose mild primary hyperparathyroidism. We determined the importance of this factor in a Belgian population. DESIGN, PATIENTS, METHODS: Intact PTH and 25(OH)D were measured in 261 healthy controls (18-65 years, winter/summer). They were classified as 25(OH)D replete (50-153 nmol/l; n = 129) or deplete (8-50 nmol/l; n = 132). PTH was determined in 49 patients with surgically proven primary hyperparathyroidism. PTH thresholds for 95% specificities and corresponding sensitivities were computed from both 25(OH)D replete and deplete receiver operating characteristic (ROC) curves. The 95% bivariate reference ellipses, relating PTH to calcium for 25(OH)D replete and deplete controls, were compared to the PTH/calcium pairs of patients with primary hyperparathyroidism. RESULTS: Parathyroid hormone correlated with 25(OH)D (r = 0.3232; P < 0.0001). PTH normative values were 20% lower in 25(OH)D replete than deplete controls (P < 0.0001). PTH thresholds, providing 95% specificities for primary hyperparathyroidism diagnosis, were 7.6 pmol/l and 5.8 pmol/l, using ROC curves derived from 25(OH)D deplete or replete controls, respectively. Corresponding sensitivities were of 56%vs 88%, respectively (P < 0.05). The 95% PTH/calcium bivariate reference ellipses for?deplete and replete 25(OH)D controls differed, but the PTH/calcium pairs of patients with primary hyperparathyroidism did not overlap these ellipses. CONCLUSION: For a given specificity, primary hyperparathyroidism diagnostic parathyroid hormone thresholds were lower and sensitivities higher using ROC curves, derived from 25(OH)D replete vs deplete controls. The 25(OH)D status does not affect the efficiency of primary hyperparathyroidism diagnosis, using bivariate PTH/calcium reference density ellipses. PMID- 22066865 TI - Well-defined binuclear chiral spiro copper catalysts for enantioselective N-H insertion. AB - An asymmetric N-H insertion of alpha-diazoesters with anilines catalyzed by well defined copper complexes of chiral spiro bisoxazoline ligands was studied in detail. The copper-catalyzed asymmetric N-H insertion of a wide range of alpha alkyl-alpha-diazoacetates with anilines was accomplished with excellent enantioselectivity (up to 98% ee) and provided an efficient method for the preparation of optically active alpha-amino acid derivatives. A correlation study of the electronic properties of the substrates with the enantioselectivity of the N-H insertion reaction supports a stepwise insertion mechanism, and the significant first-order kinetic isotope effect proves that the proton transfer is most likely the rate-limiting step. A binuclear chiral spiro copper catalyst having 14-electron copper centers, a trans coordination model, a perfect C(2) symmetric chiral pocket, and significant Cu-Cu interaction was isolated and extensively studied. The novel structure of the binuclear chiral spiro copper catalyst leads to unique reactivity as well as enantioselectivity in the N-H insertion reaction. PMID- 22066866 TI - Proanthocyanidin-rich extracts from cranberry fruit (Vaccinium macrocarpon Ait.) selectively inhibit the growth of human pathogenic fungi Candida spp. and Cryptococcus neoformans. AB - Cranberry ( Vaccinium macrocarpon ) has been shown in clinical studies to reduce infections caused by Escherichia coli and other bacteria, and proanthocyanidins are believed to play a role. The ability of cranberry to inhibit the growth of opportunistic human fungal pathogens that cause oral, skin, respiratory, and systemic infections has not been well-studied. Fractions from whole cranberry fruit were screened for inhibition of five Candida species and Cryptococcus neoformans , a causative agent of fungal meningitis. Candida glabrata , Candida lusitaniae , Candida krusei , and Cryptococcus neoformans showed significant susceptibility to treatment with cranberry proanthocyanidin fractions in a broth microdilution assay, with minimum inhibitory concentrations as low as 1 MUg/mL. MALDI-TOF MS analysis of subfractions detected epicatechin oligomers of up to 12 degrees of polymerization. Those containing larger oligomers caused the strongest inhibition. This study suggests that cranberry has potential as an antifungal agent. PMID- 22066867 TI - The antimicrobial peptide LL-37 is anti-inflammatory and proapoptotic in human periodontal ligament cells. AB - BACKGROUND AND OBJECTIVE: The antimicrobial peptide LL-37 is expressed in periodontal tissue, and variations in LL-37 levels have been associated with periodontal disease. The effects of LL-37 on periodontal ligament cell function have not been described before. Here, we assess anti-inflammatory properties of LL-37 and investigate the effects of LL-37 on cell differentiation, cell proliferation and apoptosis in human periodontal ligament cells. MATERIAL AND METHODS: Periodontal ligament cells were obtained from teeth extracted for orthodontic reasons. Cytokine (interleukin-6) and chemokine (monocyte chemoattractant protein-1) expression was determined by quantitative PCR, cell differentiation by alkaline phosphatase activity, cell proliferation by counting cells in a Burker chamber, DNA synthesis by incorporation of radiolabeled thymidine and apoptosis by cell morphology and activated caspase 3 quantities. RESULTS: Treatment with 0.1 and 1 MUm of LL-37 totally reversed lipopolysaccharide-induced monocyte chemoattractant protein-1 expression and suppressed lipopolysaccharide-induced interleukin-6 expression by 50-70%. LL-37 had no effect on alkaline phosphatase activity. Incubation with 8 MUm LL-37 strongly reduced cell number. DNA synthesis was attenuated by about 90% in response to 8 MUm LL-37, confirming its antiproliferative effect. Cell morphology was altered in an apoptosis-like fashion in cells treated with 8 MUm LL-37. Furthermore, the quantity of activated caspase 3 was increased in cells treated with 1 and 8 MUm of LL-37, suggesting apoptosis. CONCLUSION: LL-37 strongly attenuates lipopolysaccharide-induced cytokine and chemokine expression and, in high concentrations, reduces cell proliferation through inhibition of DNA synthesis and by promoting apoptosis in human periodontal ligament cells. PMID- 22066868 TI - Combating biofilms. AB - Biofilms are complex microbial communities consisting of microcolonies embedded in a matrix of self-produced polymer substances. Biofilm cells show much greater resistance to environmental challenges including antimicrobial agents than their free-living counterparts. The biofilm mode of life is believed to significantly contribute to successful microbial survival in hostile environments. Conventional treatment, disinfection and cleaning strategies do not proficiently deal with biofilm-related problems, such as persistent infections and contamination of food production facilities. In this review, strategies to control biofilms are discussed, including those of inhibition of microbial attachment, interference of biofilm structure development and differentiation, killing of biofilm cells and induction of biofilm dispersion. PMID- 22066869 TI - Validating T-RFLP as a sensitive and high-throughput approach to assess bacterial diversity patterns in human anterior nares. AB - While recent works aimed to thoroughly characterize the bacterial community of the human anterior nares of a few candidates, this work sought to analyse a greater cross-section by sampling 100 volunteers. After optimizing and validating the method of terminal restriction fragment length polymorphism against six previously pyrosequenced samples, abundant species could be discriminated and their relative abundances measured in a high-throughput manner. The 100 volunteers could be statistically clustered into 12 groups, where two-thirds of volunteers shared more than 40% similarity in respect to their bacterial community structure, while the remaining third clustered into smaller groups being dominated by Dolosigranulum pigrum, Moraxella spp. or Staphylococcus aureus. Moraxella spp. was present predominantly in women rather than in men. The use of network analysis charting bacterial ecological co-occurrences revealed new evidence of likely positive associations between some core human nasal species. So, in the age of post 'omics' and 'deep sequencing', there is still a place for these well-tried and well-tested methods that can offer a rapid, reproducible and economical alternative, whereby also yielding valuable new information. PMID- 22066870 TI - Factors influencing weaning from mechanical ventilation in elderly patients with severe pneumonia. AB - AIMS: The purpose of this study was to determine the factors that adversely affect the weaning of elderly patients with community-acquired pneumonia from mechanical ventilation. METHODS: This study retrospectively investigated the medical records of 71 elderly patients (65 years or older) who were admitted to the hospital because of community-acquired pneumonia and required mechanical ventilation between January 2003 and December 2007. The patients were divided into two groups: group A, which included 33 patients who were successfully weaned from mechanical ventilation, and group B, which included 38 patients who could not be weaned from mechanical ventilation. The study compared the patients' background, vital signs, and laboratory and bacteriological examinations at the beginning of mechanical ventilation. A multiple logistic regression analysis was performed to identify the factors associated with difficulties in weaning patients from mechanical ventilation. RESULTS: In group B, there were significantly more smokers (P < 0.05) and more patients with emphysematous changes on thoracic CT (P < 0.05). In group A, the concentrations of total serum protein (P < 0.05) and albumin (P < 0.05) were significantly higher. A multiple logistic regression analysis revealed that patients with community-acquired pneumonia who showed emphysematous changes on thoracic CT (OR = 4.92, 95%CI 1.08 22.46) and/or a low concentration of serum albumin <3.0 g/dL (OR = 4.25, 95%CI 1.17-15.45) had difficulty being weaned from mechanical ventilation. CONCLUSION: Our study suggests that elderly patients with community-acquired pneumonia with emphysematous changes on thoracic CT and/or a low concentration of serum albumin level have difficulty being weaned from mechanical ventilation. PMID- 22066871 TI - A method for the reductive scission of heterocyclic thioethers. AB - A mild, chemoselective, and generally high-yielding method for the reductive scission of heterocyclic thioethers is described. Suitable heterocycles have a thioether substituent at the 2-position relative to a ring heteroatom. The convenient and straightforward method is demonstrated with reactants which are not compatible with the standard Raney nickel conditions such as sulfides, sulfones, and thiophenes. In addition, benzyl esters, benzyl amides, and benzyl carbamates are tolerated by the reductive reaction conditions. PMID- 22066872 TI - Reviews on animal diseases recently published in other journals. PMID- 22066874 TI - Hybrid swarm between divergent lineages of mule deer (Odocoileus hemionus). AB - Studies of hybrid zones have revealed an array of evolutionary outcomes, yet the underlying structure is typically characterized as one of three types: a hybrid zone, a hybrid swarm or a hybrid taxon. Our primary objective was to determine which of these three structures best characterizes a zone of hybridization between two divergent lineages of mule deer (Odocoileus hemionus), mule deer and black-tailed deer. These lineages are morphologically, ecologically and genetically distinct, yet hybridize readily along a zone of secondary contact between the east and west slopes of the Cascade Mountains (Washington and Oregon, USA). Using microsatellite and mitochondrial DNA, we found clear evidence for extensive hybridization and introgression between lineages, with varying degrees of admixture across the zone of contact. The pattern of hybridization in this region closely resembles a hybrid swarm; based on data from 10 microsatellite loci, we detected hybrids that extend well beyond the F1 generation, did not detect linkage disequilibrium at the centre of the zone and found that genotypes were associated randomly within the zone of contact. Introgression was characterized as bidirectional and symmetric, which is surprising given that the zone of contact occurs along a sharp ecotone and that lineages are characterized by large differences in body size (a key component of mating success). Regardless of the underlying mechanisms promoting hybrid swarm maintenance, it is clear that the persistence of a hybrid swarm presents unique challenges for management in this region. PMID- 22066882 TI - Using cognitive-behavioural techniques to improve exclusive breastfeeding in a low-literacy disadvantaged population. AB - Despite being an important component of Pakistan's primary health care programme, the rates of exclusive breastfeeding at 6 months remain among the lowest in the world. Low levels of literacy in women and deeply held cultural beliefs and practices have been found to contribute to the ineffectiveness of routine counselling delivered universally by community health workers in Pakistan. We aimed to address this by incorporating techniques of cognitive-behavioural therapy (CBT) into the routine counselling process. We conducted qualitative studies of stakeholders' opinions (mothers, community health workers, their trainers and programme managers) and used this data to develop a psycho educational approach that combined education with techniques of CBT that could be integrated into the health workers' routine work. The workers were trained to use this approach and feedback was obtained after implementation. The new intervention was successfully integrated into the community health worker programme and found to be culturally acceptable, feasible and useful. Incorporating techniques of CBT into routine counselling may be useful to promote health behaviours in traditional societies with low literacy rates. PMID- 22066883 TI - Antibiotic susceptibility and intracellular localization of Diplorickettsia massiliensis. AB - Diplorickettsia massiliensis is an obligate intracellular bacterium from the Coxiellaceae family recently isolated from Ixodes ricinus ticks. The inhibitory effects of antimicrobial agents were assessed by two different methods, immunofluorescence and Gimenez staining assay. Different markers (EEA1, Lamp-1, Cathepsin D, and LysoTracker Red DND99) were used to reveal the nature of the vacuole containing the bacterium. Ciprofloxacin, levofloxacin, and rifampin had MIC values of 2 lg mL(-1). We found that 4 lg mL(-1) of Doxycycline inhibited the growth of D. massiliensis strain. Surprisingly, D. massiliensis was resistant to chloramphenicol up to the concentration of 64 lg mL(-1). We found that penicillin G, ammonium chloride, gentamycin, omeprazole, bafilomycin A1, and chloroquine were not active against D. massiliensis. Studies performed with markers EEA1, Lamp-1, Cathepsin D, and LysoTracker Red DND99 showed that D. massiliensis is localized within an acidic compartment that is not an early phagosome, but a late phagosome or a phagolysosome. Gimenez staining stays a good method that will work with a very low number of bacteria and can be used to determine the MICs of new therapeutic antibiotics precisely. The resistance profile of D. massiliensis was found to be quite unusual for intracellular Gram-negative bacterium with marked resistance to chloramphenicol. Despite of localization in acidic compartment, pH neutralizing agents do not significantly inhibit intracellular growth of bacterium. The results of these studies prove that antibiotic resistance does not depend on pH of vacuole. This pH-related mechanism seems not to play a contributing role in the overall resistance of D. massiliensis. PMID- 22066884 TI - Chemoprotective effect of all-trans retinoic acid (ATRA) on oxidative stress and lung metastasis induced by benzo(a)pyrene. AB - Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of cancer. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A under the family retinoids, derived by irreversible oxidation of retinol (vitamin A), the parent compound for all natural retinoids. The aim of the present study is to divulge the chemopreventive and chemoprotective nature of ATRA during benzo(a)pyrene (B(a)P) induced lung cancer development in BALB/c mice. Administration of B(a)P (50 mg/kg body weight) to mice resulted in increased lipid peroxides (LPO), lipid hydroperoxides (LOOH) and nitric oxide (NO) with concomitant decrease in the levels of tissue anti-oxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and vitamin C. ATRA supplementation (0.585 mg/kg body weight) attenuated all these alterations, which indicates the anti-cancer effect that was further confirmed by histopathological analysis. Overall, the above data show that the anti-cancer effect of ATRA is more pronounced when used as an chemopreventive agent against B(a)P-induced lung carcinogenesis. PMID- 22066885 TI - Chloroflexi bacteria are more diverse, abundant, and similar in high than in low microbial abundance sponges. AB - Some marine sponges harbor dense and phylogenetically complex microbial communities [high microbial abundance (HMA) sponges] whereas others contain only few and less diverse microorganisms [low microbial abundance (LMA) sponges]. We focused on the phylum Chloroflexi that frequently occurs in sponges to investigate the different associations with three HMA and three LMA sponges from New Zealand. By applying a range of microscopical and molecular techniques a clear dichotomy between HMA and LMA sponges was observed: Chloroflexi bacteria were more abundant and diverse in HMA than in LMA sponges. Moreover, different HMA sponges contain similar Chloroflexi communities whereas LMA sponges harbor different and more variable communities which partly resemble Chloroflexi seawater communities. A comprehensive phylogenetic analysis of our own and publicly available sponge-derived Chloroflexi 16S rRNA gene sequences (> 780 sequences) revealed the enormous diversity of this phylum within sponges including 29 sponge-specific and sponge-coral clusters (SSC/SCC) as well as a 'supercluster' consisting of > 250 sponge-derived and a single nonsponge-derived 16S rRNA gene sequence. Interestingly, the majority of sequences obtained from HMA sponges, but only a few from LMA sponges, fell into SSC/SCC clusters. This indicates a much more specific association of Chloroflexi bacteria with HMA sponges and suggests an ecologically important role for these prominent bacteria. PMID- 22066886 TI - An analysis of seismic risk from a tourism point of view. AB - Global awareness of natural calamities increased after the destructive Indian Ocean tsunami of December 2004, largely because many foreigners lost their lives, especially in Thailand. This paper explores how best to communicate the seismic risk posed by different travel destinations to crisis management personnel in tourists' home countries. The analysis of seismic risk should be straightforward enough for non-specialists, yet powerful enough to identify the travel destinations that are most at risk. The output for each location is a point in 3D space composed of the natural and built-up environment and local tourism. The tourism-specific factors can be tailored according to the tourists' nationality. The necessary information can be collected from various directories and statistics, much of it available over the Internet. The output helps to illustrate the overall seismic risk conditions of different travel destinations, allows for comparison across destinations, and identifies the places that are most at risk. PMID- 22066887 TI - Prognostic value of pulsed tissue Doppler imaging for the assessment of left ventricular systolic function in patients with nonischemic dilated cardiomyopathy. AB - There is still some debate regarding the prognostic significance of left ventricular longitudinal systolic dysfunction as assessed by tissue Doppler (TD) imaging in patients with chronic heart failure (HF), since previous studies have included patients with postischemic wall motion abnormalities. Thus, this study was designed to ascertain whether TD-derived longitudinal systolic dysfunction may influence the outcome of patients with nonischemic chronic HF. In 200 consecutive patients with chronic HF secondary to dilated cardiomyopathy and no history of ischemic heart disease, peak systolic mitral annular velocity (S(m) ) was measured by pulsed TD at the septal and lateral annular sites. The end points were cardiac death or hospitalization for worsening HF. Mean follow-up duration was 30 months. In a time independent analysis, averaged S(m) calculated as the average of septal and lateral S(m) , resulted to be a significant predictor of outcome in the study population (area under receiver-operator characteristic curve: cardiovascular death, 0.69, P < 0.0001; cardiovascular events, 0.64, P = 0.0005). In a time-dependent analysis, average S(m) was associated with both cardiovascular death (hazard ratio 0.832, P = 0.0019) and cardiovascular events (hazard ratio 0.904, P = 0.039), independently of other clinical risk factors and echocardiographic parameters of systolic function. Septal S(m) but not lateral S(m) was independently associated with the outcome measures. In conclusion, the assessment of systolic mitral annular velocity by pulsed TD is a useful indicator for prognostic stratification of patients with nonischemic dilated cardiomyopathy and chronic HF. PMID- 22066888 TI - Nuclear accident like Fukushima unlikely in the rest of the world? PMID- 22066889 TI - Non-contraceptive benefits of hormonal contraception: time for renewed awareness. PMID- 22066890 TI - Does structured counselling influence combined hormonal contraceptive choice? AB - OBJECTIVE: To assess the effect of structured counselling on women's contraceptive decisions and to evaluate gynaecologists' perceptions of comprehensive contraceptive counselling. METHODS: Belgian women (18-40 years old) who were considering using a combined hormonal contraceptive (CHC) were counselled by their gynaecologists about available CHCs (combined oral contraceptive [COC], transdermal patch, vaginal ring), using a comprehensive leaflet. Patients and gynaecologists completed questionnaires that gathered information on the woman's pre- and post-counselling contraceptive choice, her perceptions, and the reasons behind her post-counselling decision. RESULTS: The gynaecologists (N=121) enrolled 1801 eligible women. Nearly all women (94%) were able to choose a method after counselling (53%, 5%, and 27% chose the COC, the patch, and the ring, respectively). Counselling made many women (39%) select a different method: patch use increased from 3% to 5% (p<0.0001); ring use tripled (from 9% to 27%, p<0.0001). Women who were undecided before counselling most often opted for the method their gynaecologist recommended, irrespective of counselling. CONCLUSION: Counselling allows most women to select a contraceptive method; a sizeable proportion of them decide on a method different from the one they initially had in mind. Gynaecologists? preferences influenced the contraceptive choices of women who were initially undecided regarding the method to use. PMID- 22066891 TI - Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17beta-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. AB - OBJECTIVES: To compare the effects of a combined oral contraceptive (COC) containing nomegestrol acetate and 17beta-oestradiol (NOMAC/E2) on haemostasis, lipids, carbohydrate metabolism, C-reactive protein (CRP) and sex hormone-binding globulin (SHBG) with those of a COC containing levonorgestrel and ethinylestradiol (LNG/EE). METHODS: In a randomised, open-label study, 121 healthy women, 18-50 years of age, were randomly assigned to receive NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n=60) or LNG/EE (150 MUg/30 MUg) in a 21/7 day regimen (n=61) for six cycles. The primary outcome was the change from baseline to cycle 6 for all indices. RESULTS: All parameters were similar at baseline between the two groups. Over six cycles, NOMAC/E2 had less effect on most haemostatic indices than LNG/EE. Lipids were essentially unchanged with NOMAC/E2, whereas with LNG/EE high-density lipoprotein cholesterol decreased and low-density lipoprotein cholesterol and triglycerides slightly increased. NOMAC/E2 induced negligible changes in glucose and insulin parameters, in contrast to LNG/EE. A much smaller increase in CRP was observed with NOMAC/E2 than with LNG/EE. NOMAC/E2 was associated with a greater increase in SHBG. CONCLUSIONS: The monophasic COC NOMAC/E2 had less influence on haemostasis, lipids and carbohydrate metabolism than the COC LNG/EE. PMID- 22066892 TI - Effects of Anethum graveolens L. on fertility in male rats. AB - OBJECTIVES: The effects of Anethum graveolens seed extract on fertility of male rats were investigated. METHODS: Male Wistar rats were divided into five groups according to the treatment they received during 42 days: control, low dose (0.5 g/kg) and high dose (5 g/kg) of aqueous extracts, and low dose (0.045 g/kg) and high dose (0.45 g/kg) of ethanol extracts of Anethum graveolens seed. Sperm count and motility and testosterone concentration were measured. Sections of the testes, epididymis, and seminal vesicles were stained with peroxidase-conjugated lectins of Ulex europaeus agglutinin, peanut agglutinin, Dolichos biflorus agglutinin, soy bean agglutinin and concanavalin A. The treated male rats were mated with females and the crown-rump lengths and weights of their newborn pups were measured. RESULTS: No significant differences in sperm count, sperm motility or testosterone concentration were observed in the experimental groups. However, female rats did not become pregnant after mating with rats given the high dose of the ethanol extract. The distribution of terminal sugars on the epithelial surface of the reproductive structures decreased in the experimental groups. CONCLUSION: Anethum graveolens extract decreased fertility rate by modifying some terminal sugars on the cell surface of male reproductive organs involved in sperm maturation, capacitation and oocyte recognition. PMID- 22066894 TI - Transient discoloration of the coronal fragment in intra-alveolar root fractures. AB - BACKGROUND: Root fractures are a relatively rare type of injury with frequencies of 0.5-7% of traumatized permanent teeth. It is well known that teeth with intra alveolar root fractures have a good prognosis. The pulp remains vital in about 80% of these teeth. If pulp necrosis develops, this normally only occurs in the coronal fragment. Although several studies on intra-alveolar root fractures have been published during the last decades, none have mentioned that transient discoloration can occur. The aim of our study was to study the frequency and prognosis for intra-alveolar root fractures with discoloration. MATERIAL AND METHODS: The material consisted of 42 permanent incisors from 21 boys and 18 girls aged 7-19 years (mean = 12.7, median 12.0). In two girls and one boy, two incisors exhibited concurrent intra-alveolar root fractured. The follow-up period ranged from 1 to 9 years. The colour changes were determined at each control by transillumination of the clinical crown from the facial and palatal surfaces. Electrometric sensibility was evaluated and compared to the values of adjacent teeth using an electric pulp tester. At the final clinical and radiographic control, the type of healing was registered. RESULTS: Discoloration was found in nine teeth. The root development was completed in all these teeth. The discoloration disappeared within 4 weeks to 6 months in eight teeth. The sensibility, which was lost at the injury, followed the changes in discoloration, and all teeth had regained normal sensibility when the discoloration had disappeared. Only one tooth, which showed a greyish hue, developed pulp necrosis. CONCLUSION: Transient discoloration in intra-alveolar fractures is relatively common and is indicative of a good prognosis for healing. PMID- 22066895 TI - Synthesis of 2-(trifluoromethyl)oxazoles from beta-monosubstituted enamines via PhI(OCOCF3)2-mediated trifluoroacetoxylation and cyclization. AB - Treatment of beta-monosubstituted enamines with phenyliodine bis(trifluoroacetate) (PIFA) was found to give a variety of 4,5-disubstituted 2 (trifluoromethyl)oxazoles. This approach allows the incorporation of the trifluoromethyl moiety in PIFA into the final products, which presumably takes place via the oxidative beta-trifluoroacetoxylation of the enamine substrates followed by subsequent intramolecular cyclization. PMID- 22066896 TI - Aspirations and realities of love, marriage and education among Hmong women. AB - Stereotypical portrayals of the Hmong in Vietnam emphasize their apparently exotic customs related to sexual relationships and marriage and their alleged backwardness and resistance to change. Yet their history shows their ability to respond to changing socioeconomic contexts. This study details practices and aspirations concerning love, marriage and education among different generations of White Hmong women in the northern mountains of Vietnam, with particular attention to the perspectives of young women. We found a diversity of ideas and identified certain rapidly changing practices regarding marriage. Forced marriage through 'wife-snatching' was reported to have always been rare and its meaning and prevalence has seemingly been misunderstood by outsiders. Bride price payment was reported to be an important element of most Hmong marriages. Hmong girls studying at high school and secondary level were found to have particular aspirations pertaining to their marriage, education and career, but lacked confidence in their abilities to create their desired future. Findings also reveal how patrilocal residence following marriage places young women under the strict control of their husbands and parents-in-law, which is likely to contribute to their lack of self-esteem and sense of autonomy. PMID- 22066897 TI - Profiles of liquid drops at the bottom of cylindrical fibers standing on flat substrates. AB - Based on Carroll's derivation that describes a symmetric liquid drop sitting on an infinite cylindrical fiber and the shape of the drop, we have extended the derivation to describe a drop located at the bottom of cylindrical fibers standing on flat substrates. According to our derivation, the shape of the drop forms a bell as predicted by Carroll but is cut off by the flat substrate. This theoretical prediction was verified experimentally using water, ethylene glycol, and Kaydol drops on glass, nylon and polypropylene cylindrical fibers, and on polytetrafluoroethylene (PTFE) and polyester (PET) flat substrates. We found that only four parameters are required to obtain agreement between the theoretical shape and the observed shape: the drop volume, the fiber radius, the liquid-fiber contact angle, and liquid-flat substrate contact angle. PMID- 22066898 TI - Vaginal cone for postmenopausal women with stress urinary incontinence: randomized, controlled trial. AB - OBJECTIVE: To investigate the effect of vaginal cones and pelvic floor muscle training (PFTM) in postmenopausal women with stress urinary incontinence. METHODS: This randomized, controlled study included postmenopausal women, who complained of stress urinary incontinence. Forty-five women were allocated to three groups: a group given therapy with vaginal cones (n = 15), a group receiving therapy with PFTM (n = 15), and the control group (n = 15). Subjects in the intervention groups were treated for 6 weeks with twice-weekly sessions of 40 min. Women in the vaginal cone group carried out the pelvic floor muscle strengthening with vaginal cones. The control group did not receive any treatment during the corresponding time. They were evaluated before, at the end of treatment and 6 weeks after treatment completion for primary outcomes (1-h pad test for urinary loss and pelvic floor muscle pressure) and secondary outcomes (quality of life with King's Health Questionnaire, satisfaction with treatment, and continuity of training). RESULTS: For urinary leakage, there were statistical differences between the treated groups and the control group at the end of treatment and 6 weeks after treatment (all p < 0.01; effect size: vaginal cone group 20.97; PFMT group 20.96). The same behavior was shown for treatment with pelvic floor muscle pressure (all p < 0.01; effect size: vaginal cone group 22.58; PFMT group 21.68). There were no differences between the vaginal cone and PFMT groups in any of the evaluations. In outcomes for quality of life, significant differences were observed for incontinence impact and gravity domains when both treated groups were compared with the control group after treatment. Both groups reported similar satisfaction levels and the vaginal cone group demonstrated lower training continuity. CONCLUSION: Based on this study, there were similar positive results for treatment with the vaginal cone and pelvic floor muscle training for urinary leakage, pelvic floor muscle pressure and quality of life for postmenopausal women with stress urinary incontinence after 6 weeks. PMID- 22066899 TI - Nickel-catalyzed Heck-type reactions of benzyl chlorides and simple olefins. AB - Nickel-catalyzed intermolecular benzylation and heterobenzylation of unactivated alkenes to provide functionalized allylbenzene derivatives are described. A wide range of both the benzyl chloride and alkene coupling partners are tolerated. In contrast to analogous palladium-catalyzed variants of this process, all reactions described herein employ electronically unbiased aliphatic olefins (including ethylene), proceed at room temperature, and provide 1,1-disubstituted olefins over the more commonly observed 1,2-disubstituted olefins with very high selectivity. PMID- 22066900 TI - Characterization of the gene encoding pisatin demethylase (FoPDA1) in Fusarium oxysporum. AB - The pea pathogen Fusarium oxysporum f. sp. pisi is able to detoxify pisatin produced as a defense response by pea, and the gene encoding this detoxification mechanism, FoPDA1, was 82% identical to the cytochrome P450 pisatin demethylase PDA1 gene in Nectria haematococca. A survey of F. oxysporum f. sp. pisi isolates demonstrated that, as in N. haematococca, the PDA gene of F. oxysporum f. sp. pisi is generally located on a small chromosome. In N. haematococca, PDA1 is in a cluster of pea pathogenicity (PEP) genes. Homologs of these PEP genes also were found in the F. oxysporum f. sp. pisi isolates, and PEP1 and PEP5 were sometimes located on the same small chromosomes as the FoPDA1 homologs. Transforming FoPDA1 into a pda(?) F. oxysporum f. sp. lini isolate conferred pda activity and promoted pathogenicity on pea to some transformants. Different hybridization patterns of FoPDA1 were found in F. oxysporum f. sp. pisi but these did not correlate with the races of the fungus, suggesting that races within this forma specialis arose independently of FoPDA1. FoPDA1 also was present in the formae speciales lini, glycines, and dianthi of F. oxysporum but they had mutations resulting in nonfunctional proteins. However, an active FoPDA1 was present in F. oxysporum f. sp. phaseoli and it was virulent on pea. Despite their evolutionary distance, the amino acid sequences of FoPDA1 of F. oxysporum f. sp. pisi and F. oxysporum f. sp. phaseoli revealed only six amino acid differences, consistent with a horizontal gene transfer event accounting for the origin of these genes. PMID- 22066901 TI - Synthesis of the flavonoid-induced lipopolysaccharide of Rhizobium Sp. strain NGR234 requires rhamnosyl transferases encoded by genes rgpF and wbgA. AB - In the presence of flavonoids, Rhizobium sp. strain NGR234 synthesizes a new lipopolysaccharide (LPS), characterized by a rhamnan O-antigen. The presence of this rhamnose-rich LPS is important for the establishment of competent symbiotic interactions between NGR234 and many species of leguminous plants. Two putative rhamnosyl transferases are encoded in a cluster of genes previously shown to be necessary for the synthesis of the rhamnose-rich LPS. These two genes, wbgA and rgpF, were mutated. The resulting mutant strains synthesized truncated rough LPS species rather than the wild-type rhamnose-rich LPS when grown with flavonoids. Based on the compositions of these purified mutant LPS species, we inferred that RgpF is responsible for adding the first one to three rhamnose residues to the flavonoid-induced LPS, whereas WbgA is necessary for the synthesis of the rest of the rhamnan O-antigen. The NGR234 homologue of lpsB, which, in other bacteria, encodes a glycosyl transferase acting early in synthesis of the core portion of LPS, was identified and also mutated. LpsB was required for all the LPS species produced by NGR234, in the presence or absence of flavonoids. Mutants (i.e., of lpsB and rgpF) that lacked any portion of the rhamnan O-antigen of the induced LPS were severely affected in their symbiotic interaction with Vigna unguiculata, whereas the NGR?wbgA mutant, although having very few rhamnose residues in its LPS, was able to elicit functional nodules. PMID- 22066902 TI - The iturin-like lipopeptides are essential components in the biological control arsenal of Bacillus subtilis against bacterial diseases of cucurbits. AB - The antibacterial potential of four strains of Bacillus subtilis, UMAF6614, UMAF6619, UMAF6639, and UMAF8561, previously selected on the basis of their antifungal activity and efficacy against cucurbit powdery mildew, was examined. Among these strains, UMAF6614 and UMAF6639 showed the highest antibacterial activity in vitro, especially against Xanthomonas campestris pv. cucurbitae and Pectobacterium carotovorum subsp. carotovorum. These strains produced the three families of lipopeptide antibiotics known in Bacillus spp.: surfactins, iturins, and fengycins. Using thin-layer chromatography analysis and direct bioautography, the antibacterial activity could be associated with iturin lipopeptides. This result was confirmed by mutagenesis analysis using lipopeptide-defective mutants. The antibacterial activity was practically abolished in iturin-deficient mutants, whereas the fengycin mutants retained certain inhibitory capabilities. Analyses by fluorescence and transmission electron microscopy revealed the cytotoxic effect of these compounds at the bacterial plasma membrane level. Finally, biological control assays on detached melon leaves demonstrated the ability of UMAF6614 and UMAF6639 to suppress bacterial leaf spot and soft rot; accordingly, the biocontrol activity was practically abolished in mutants deficient in iturin biosynthesis. Taken together, our results highlight the potential of these B. subtilis strains as biocontrol agents against fungal and bacterial diseases of cucurbits and the versatility of iturins as antifungal and antibacterial compounds. PMID- 22066904 TI - Stereoselective syntheses of all stereoisomers of lariciresinol and their plant growth inhibitory activities. AB - All stereoisomers of lariciresinol were synthesized to examine the effect of stereochemistry on plant growth. Configuration of benzylic 7-positions was constructed through S(N)1 or S(N)2 intramolecular etherification. 8- and 8' position configurations were established from the starting material except for all cis stereoisomers, the 8-position configurations of which were achieved by employing stereoselective hydroboration. (-)-Lariciresinol and its 7S,8S,8'R stereoisomer inhibited the root growth of Italian ryegrass to 51-55% relative to the negative control, whereas other stereoisomers had less effect. These results demonstrate that the stereochemistry of lignans is one of the important factors influencing their inhibitory activity. PMID- 22066905 TI - Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly. AB - BACKGROUND: Primary, preoperative medical treatment is an option in selected patients with acromegaly, but a subset of patients respond poorly. Valid prediction of response to somatostatin analogues (SA) might thus alter treatment stratification. The aims of this study were to assess whether T2 signal intensity could determine long-term response to first-line SA treatment and to assess clinical and biochemical baseline characteristics, as well as histological subtype in relation to the magnetic resonance imaging (MRI) appearances. METHODS: In 45 newly diagnosed patients, T2-weighted signal intensity of the tumour was classified into hypo-, iso- or hyperintense. Biochemical and clinical baseline variables for the three groups were compared. In 25 patients primarily treated with long-acting SA for a median of 6 months [interquartile range (IQR):155-180 days], GH and IGF-1 reduction was assessed, and in 34 cases, immunohistochemical granulation pattern was evaluated. RESULTS: The results showed that 12 (27%) adenomas were hypointense, 15 (33%) isointense and 18 (40%) hyperintense. Median IGF-1 [ratio IGF-1/ULN; (upper limit of normal)] was 3.5 (2.3-4.9), 2.9 (2.6-3.8) and 1.9 (1.3-2.6), respectively (P = 0.006 for difference between groups). Median GH values (MUg/l) of a 3- to 5-point profile were 17.5 (6.1-35), 9.3 (6.0-32.5) and 4.1 (1.5-8.3), (P = 0.025). Median IGF-1 reduction (% of baseline) after first-line SA treatment was 51 (49-70), 36 (19-74) and 13 (5-42) (P = 0.03); median reduction in GH (% of baseline) was 86 (72-94), 78 (62-85) and 46 (1-70) (P = 0.02). T2 hyperintensity was associated with sparse granulation pattern on immunohistochemistry. CONCLUSION: In patients with acromegaly, T2 signal intensity at diagnosis correlates with histological features and predicts biochemical outcome of first-line SA treatment. PMID- 22066906 TI - Lifetime return on investment increases with leaf lifespan among 10 Australian woodland species. AB - * Co-occurring species often differ in their leaf lifespan (LL) and it remains unclear how such variation is maintained in a competitive context. Here we test the hypothesis that leaves of long-LL species yield a greater return in carbon (C) fixed per unit C or nutrient invested by the plant than those of short-LL species. * For 10 sympatric woodland species, we assessed three-dimensional shoot architecture, canopy openness, leaf photosynthetic light response, leaf dark respiration and leaf construction costs across leaf age sequences. We then used the YPLANT model to estimate light interception and C revenue along the measured leaf age sequences. This was done under a series of simulations that incorporated the potential covariates of LL in an additive fashion. * Lifetime return in C fixed per unit C, N or P invested increased with LL in all simulations. * In contrast to other recent studies, our results show that extended LL confers a fundamental economic advantage by increasing a plant's return on investment in leaves. This suggests that time-discounting effects, that is, the compounding of income that arises from quick reinvestment of C revenue, are key in allowing short-LL species to succeed in the face of this economic handicap. PMID- 22066907 TI - Design of chiral bis-phosphoric acid catalyst derived from (R)-3,3'-di(2-hydroxy 3-arylphenyl)binaphthol: catalytic enantioselective Diels-Alder reaction of alpha,beta-unsaturated aldehydes with amidodienes. AB - Chiral bis-phosphoric acid 1 was designed to identify a new class of structural features in chiral Bronsted acid catalysts. X-ray diffraction analysis revealed the single atropisomer 1, bearing S axial chirality at 3,3'-biaryl substituents on (R)-binaphthyl and intramolecular hydrogen bonding between the two phosphoric acid moieties. The newly designed bis-phosphoric acid 1 was evaluated in the Diels-Alder reaction of alpha,beta-unsaturated aldehydes 4 with 1-N-acylamino-1,3 butadienes 3. After systematic variation of the catalyst substituents, as well as the N-acyl substituents of 1,3-butadiene, the use of an N-Cbz amidodiene 3a in the presence of bis-phosphoric acid 1e with a 2,4,6-tri-isopropylphenyl group was found to be optimal to yield the 1S,6R enantiomeric product 5aa in a Diels-Alder reaction of acrolein (4a). Application of this method to substituted substrates was found to be an efficient approach to the enantioselective synthesis of 3- and 3,6-substituted cyclic formylcarbamates 5. The specific character as well as the utility of 1e was further established by comparing its enantioselectivity, absolute stereochemistry, and catalytic efficiency with those of mono-phosphoric acid 2. PMID- 22066908 TI - Emotional impact of a paediatric exon-skipping therapy trial. PMID- 22066909 TI - The ligands of Numb proteins X1 and X2 are specific markers for chronic Q fever. AB - Q fever is a disease caused by Coxiella burnetii, an obligate intracellular bacterium. Acute Q fever is spontaneously resolutive and is characterized by an efficient immune response. In contrast, chronic Q fever is characterized by dysregulated immune response, as demonstrated by the failure of C. burnetii to induce lymphoproliferation and the lack of granulomas. Recently, it has been demonstrated that when co-expressed in heterologous mammalian cell lines, the ligands of Numb proteins X1 and X2 (LNX1 and LNX2) regulate the level of the T cell co-receptor CD8, which plays an essential role in T-cell-mediated immune response. We decided to investigate the expression of LNX1 and LNX2 genes in patients with acute or chronic Q fever. Interestingly, we found a high level of LNX1 and LNX2 mRNAs in endocarditis, the principal manifestation of chronic Q fever, but not in acute Q fever. Our data suggest that LNXs may be used as complementary biomarkers to follow the prognosis of chronic Q fever. PMID- 22066910 TI - Biogeography of symbiotic and other endophytic bacteria isolated from medicinal Glycyrrhiza species in China. AB - A total of 159 endophytic bacteria were isolated from surface-sterilized root nodules of wild perennial Glycyrrhiza legumes growing on 40 sites in central and northwestern China. Amplified fragment length polymorphism (AFLP) genomic fingerprinting and sequencing of partial 16S rRNA genes revealed that the collection mainly consisted of Mesorhizobium, Rhizobium, Sinorhizobium, Agrobacterium and Paenibacillus species. Based on symbiotic properties with the legume hosts Glycyrrhiza uralensis and Glycyrrhiza glabra, we divided the nodulating species into true and sporadic symbionts. Five distinct Mesorhizobium groups represented true symbionts of the host plants, the majority of strains inducing N2-fixing nodules. Sporadic symbionts consisted of either species with infrequent occurrence (Rhizobium galegae, Rhizobium leguminosarum) or species with weak (Sinorhizobium meliloti, Rhizobium gallicum) or no N2 fixation ability (Rhizobium giardinii, Rhizobium cellulosilyticum, Phyllobacterium sp.). Multivariate analyses revealed that the host plant species and geographic location explained only a small part (14.4%) of the total variation in bacterial AFLP patterns, with the host plant explaining slightly more (9.9%) than geography (6.9%). However, strains isolated from G. glabra were clearly separated from those from G. uralensis, and strains obtained from central China were well separated from those originating from Xinjiang in the northwest, indicating both host preference and regional endemism. PMID- 22066911 TI - Comparing statistical methods for quantifying drug sensitivity based on in vitro dose-response assays. AB - In vitro chemosensitivity assays are invaluable for assessing chemotherapeutic agents' effects on cancer cells. Yet the dose-response curves generated by those assays, usually approximated by four-parameter logistic (4PL) models, are oftentimes difficult to interpret, with no clear indication of which metric should be used to compare them. Here, five commonly used metrics, absolute and relative half-maximal inhibitory concentration (IC(50)), area under the dose response curve (AUC) based on trapezoidal rule and a parametric approach, and the effect at the maximal concentrations (E(max)), were compared in both simulations and real-life scenarios to evaluate their use with 4PL curves. Despite the fact that IC(50) is the most widely used metric to analyze dose-response curves, this study demonstrated that it was not the most reliable of the metrics tested. Fitted AUC showed the best overall performance in both the simulation and real life scenarios; trapezoidal AUC showed similar performance to fitted AUC in most cases. PMID- 22066912 TI - Dynamic mass redistribution assays decode surface influence on signaling of endogenous purinergic P2Y receptors. AB - Interactions with extracellular matrices (ECM) shape the signaling and functions of many types of cells and receptors, and distinct ECM coatings have been used in a wide range of substrates for drug discovery processes. Here, we investigate the influence of ECM protein coatings on the signaling of endogenous purinergic 2Y (P2Y) receptors in human embryonic kidney HEK293 cells using dynamic mass redistribution (DMR) assays enabled by label-free optical biosensor. Results showed that ECM proteins had significant impacts on the DMR characteristics, potency, and efficacy of seven P2Y agonists. This study documents the importance of surface chemistry in regulating receptor signaling. PMID- 22066913 TI - Thermal denaturation assays in chemical biology. AB - Thermal denaturation-based methods are becoming increasingly used to characterize protein stability and interactions. Recent technical advances have made these methods more suitable for high throughput screening. Reasonable throughput and the ability to perform these screens using commonly used instruments, such as RT PCR machines or simple plate readers equipped with heating devices, facilitate these experiments in almost any laboratory. Introducing an aggregation-based monitoring approach as well as alternative fluorophores has allowed the screening of a wider range of proteins, including membrane proteins, against large chemical libraries. Thermal denaturation-based methods are independent of protein function, which is especially useful for the identification of orphan protein function. Here, we review applications of thermal denaturation-based methods in characterizing protein stability and ligand binding, and also provide information on protocol modifications that may further increase throughput. PMID- 22066914 TI - Day-care service use is a risk factor for long-term care placement in community dwelling dependent elderly. AB - AIMS: To identify predictors of long-term care placement and to examine the effect of day-care service use on long-term care placement over a 36-month follow up period among community-dwelling dependent elderly. METHODS: This study was a prospective cohort analysis of 1739 community-dwelling elderly and 1442 caregivers registered in the Nagoya Longitudinal Study for Frail Elderly. Data included the clients' demographic characteristics, basic activities of daily living, comorbidities, and use of home care services, including the day-care, visiting nurse, and home-help services, as well as caregivers' demographic characteristics and care burden. Analysis of long-term care placement over 36 month was conducted using Kaplan-Meier curves and multivariate Cox proportional hazards models. RESULTS: Among the 1739 participants, 217 were institutionalized at long-term care facilities during the 36-month follow-up. Multivariate Cox regression models, adjusted for potential confounders, showed that day-care service use was significantly associated with an elevated risk for long-term care placement within the 36-month follow-up period. Participants using a day-care service two or more times/week had significantly higher relative hazard ratios than participants not using such a service. CONCLUSION: The results highlight the need for effective measures to reduce the long-term care placement of day-care service users. Policy makers and practitioners must consider implementing multidimensional support programs to reduce the caregivers' willingness to consider long-term care placement. PMID- 22066915 TI - Management of complicated crown-root fractures using intentional replantation: two case reports. AB - The management of complicated crown-root fractures is a challenge. Intentional replantation with 180 degrees rotation may be a useful procedure to overcome this problem. In Case 1, a 23-year-old woman with complicated crown-root fractured teeth #11, #21, and #22 was referred for treatment. All fractured teeth were extracted, rotated 180 degrees , and replanted in a slightly extruded position. After 3 months, root canal treatment was completed and the final restorations fabricated. At the 18-month follow up, the patient was asymptomatic, the tooth was functional, and no root resorption was observed radiographically. At the 90-month follow up, slight cervical root resorption of tooth #11 was noted. In Case 2, a 27-year-old woman with a crown-root fractured tooth #21 was referred for treatment. Despite immediate repositioning of the coronal fragment and a 2-week stabilization with a wire splint, the coronal fragment remained separated from the apical tooth segment. The apical segment was extracted, rotated 180 degrees , and replanted in a slightly extruded position. After 1 and 4 weeks, the root canal treatment was completed and the final restoration fabricated, respectively. At the 24-month follow up, the patient was asymptomatic and apical healing was completed. PMID- 22066928 TI - Snapping magnetosome chains by asymmetric cell division in magnetotactic bacteria. AB - The mechanism by which prokaryotic cells organize and segregate their intracellular organelles during cell division has recently been the subject of substantial interest. Unlike other microorganisms, magnetotactic bacteria (MTB) form internal magnets (known as magnetosome chain) for magnetic orientation, and thus face an additional challenge of dividing and equipartitioning this magnetic receptor to their daughter cells. Although MTB have been investigated more than four decades, it is only recently that the basic mechanism of how MTB divide and segregate their magnetic organelles has been addressed. In this issue of Molecular Microbiology, the cell cycle of the model magnetotactic bacterium, Magnetospirillum gryphiswaldense is characterized by Katzmann and co-workers. The authors have found that M. gryphiswaldense undergoes an asymmetric cell division along two planes. A novel wedge-like type of cellular constriction is observed before separation of daughter cells and magnetosome chains, which is assumed to help cell cope with the magnetic force within the magnetosome chain. The data shows that the magnetosome chain becomes actively recruited to the cellular division site, in agreement with the previous suggestions described by Staniland et al. (2010), and the actin-like protein MamK is likely involved in this fast polar-to-midcell translocalization. With the use of cryo-electron tomography, an arc-shaped Z ring is observed near the division site, which is assumed to trigger the asymmetric septation of cell and magnetosome chain. PMID- 22066929 TI - Simazine application inhibits nitrification and changes the ammonia-oxidizing bacterial communities in a fertilized agricultural soil. AB - s-Triazine herbicides are widely used for weed control, and are persistent in soils. Nitrification is an essential process in the global nitrogen cycle in soil, and involves ammonia-oxidizing Bacteria (AOB) and ammonia-oxidizing Archaea (AOA). In this study, we evaluated the effect of the s-triazine herbicide simazine on the nitrification and on the structure of ammonia-oxidizing microbial communities in a fertilized agricultural soil. The effect of simazine on AOB and AOA were studied by PCR-amplification of amoA genes of nitrifying Bacteria and Archaea in soil microcosms and denaturing gradient gel electrophoresis (DGGE) analyses. Simazine [50 MUg g(-1) dry weight soil (d.w.s)] completely inhibited the nitrification processes in the fertilized agricultural soil. The inhibition by simazine of ammonia oxidation observed was similar to the reduction of ammonia oxidation by the nitrification inhibitor acetylene. The application of simazine affected AOB community DGGE patterns in the agricultural soil amended with ammonium, whereas no significant changes in the AOA community were observed. The DGGE analyses strongly suggest that simazine inhibited Nitrosobacteria and specifically Nitrosospira species. In conclusion, our results suggest that the s triazine herbicide not only inhibits the target susceptible plants but also inhibits the ammonia oxidation and the AOB in fertilized soils. PMID- 22066930 TI - Regional atrial myocardial velocity in normal fetuses: evaluation by quantitative tissue velocity imaging. AB - OBJECTIVES: Quantitative tissue velocity imaging (QTVI) is a new noninvasive method that derives measurements of velocities directly from the myocardium. Data on atrial myocardial tissue velocities in normal fetuses have not been established. The objective of this study was to evaluate atrial myocardial velocity and the myocardial velocity gradient of normal fetuses by using QTVI. METHODS: We measured motion velocities of the left and right atrial wall along the long axis in 50 normal fetuses aged 21-32 weeks gestation (mean, 25.3 +/- 2.8 weeks). In all fetuses, peak myocardial velocity during early diastole (EW), atrial contraction (AW), and ventricular systole (SW) waves was recorded in the basal and mid-atrial segments. Correlation analysis was conducted between segmental velocities of the left atrium (LA) and right atrium (RA) and gestational age. RESULTS: The mean values for EW, AW, and SW of the long axis in the same right basal segment of the RA were greater than those of the LA (P < 0.01). There was a degressive gradient with velocity from the basal to superior in the atrial wall. There was a linear relationship with gestation for all basal myocardial velocities of the left and right atrial free wall (P < 0.05). However, the myocardial velocity variables of the midatrial wall showed no age-dependence. CONCLUSION: We demonstrated that QTVI is reproducible and provides readily obtained parameters that provide unique data regarding segmental atrial myocardial velocity in normal fetuses. PMID- 22066931 TI - Outcome of challenge with Coxsackievirus B4 in young mice after maternal infection with the same virus during gestation. AB - Enteroviral infections go usually unnoticed, even during pregnancy, yet some case histories and mouse experiments indicate that these viruses may be transmitted vertically. More frequently, however, transmission occurs by (fecal) contamination during and shortly after birth. The aim of this study was to investigate the effect of maternal infection in mice (1) on gravidity outcome and (2) on subsequent challenge of the offspring with the same virus. CD1 outbred female mice were infected by the oral route with coxsackievirus B4 strain E2 or mock-infected at days 4, 10, or 17 of gestation. Weight and signs of sickness were noted daily. Pups were infected at day 25 after birth (4 days postweaning). Organs (brain, pancreas, and heart) were analyzed for viral RNA and histopathology. We observed that maternal infection at day 4 or day 17 of gestation had little effect on pregnancy outcome, whereas infection at day 10 affected dams and/or offspring. Infection of pups resulted in severe inflammation of the pancreas, but only when dams were previously infected, especially at day 17. The blood glucose levels were elevated. Because no trace of infection was found at the time of challenge, a role for immunopathology is suggested. PMID- 22066932 TI - Fatty acids in serum and diet--a canonical correlation analysis among toddlers. AB - Fatty acid concentrations in blood are potential biomarkers of dietary fat intake, but methodological studies among children are scarce. The large number of fatty acids and their complex interrelationships pose a special challenge in research on fatty acids. Our target was to assess the interrelationships between the total fatty acid profiles in diet and serum of young children. The study subjects were healthy control children from the birth cohort of the Type 1 Diabetes Prediction and Prevention Study. A 3-day food record and a frozen serum sample were available from 135 children at the age of 1 year, from 133 at 2 years, and from 92 at 3 years. The relationship between dietary and serum fatty acid profiles was analysed using canonical correlation analysis. The consumption of fatty milk correlated positively with serum fatty acids, pentadecanoic acid, palmitic acid and conjugated linoleic acid (CLA) at all ages. Correlations between dietary and serum eicosapentaenoic and/or docosahexaenoic acid were observed at 2 and 3 years of age. Serum linoleic acid was positively associated with the consumption of infant formula at the age of 1 year, and with the consumption of vegetable margarine at 2 and 3 years. The results indicate a high quality of the 3-day food records kept by parents and other caretakers of the children, and suitability of non-fasting, un-fractioned serum samples for total fatty acid analyses. The correlation between intake of milk fat and serum proportion of CLA is a novel finding. PMID- 22066934 TI - Exploiting the ring strain in bicyclo[2.2.1]heptane systems for the stereoselective preparation of highly functionalized cyclopentene, dihydrofuran, pyrroline, and pyrrolidine scaffolds. AB - The high strain of bicyclic systems drives retro-condensation reactions on bridgehead substituted bicyclo[2.2.1]hept-2-enes giving rise to orthogonally functionalized cyclopentene, 2,5-dihydrofuran, and 3-pyrroline scaffolds. Retro Dieckman reactions were easily carried out on 3-tosyl-(7-carba/7-oxa/7 aza)bicyclo[2.2.1]hept-5-en-2-ones. Retro-aldol reactions of N-Boc-3-tosyl-7 azabicyclo[2.2.1]hept-5-en-2-ol and functionalized N-Boc-3-tosyl-7 azabicyclo[2.2.1]heptan-2-ols yield functionalized pyrrolidine scaffolds stereoselectively. The same reaction does not work with corresponding norbornene and 7-oxanorbornene derivatives. PMID- 22066935 TI - A framework for comparing processes of speciation in the presence of gene flow. AB - How common is speciation-with-gene-flow? How much does gene flow impact on speciation? To answer questions like these requires understanding of the common obstacles to evolving reproductive isolation in the face of gene flow and the factors that favour this crucial step. We provide a common framework for the ways in which gene flow opposes speciation and the potential conditions that may ease divergence. This framework is centred on the challenge shared by most scenarios of speciation-with-gene-flow, i.e. the need for coupling among different components of reproductive isolation. Using this structure, we review and compare the factors favouring speciation with the intention of providing a more integrated picture of speciation-with-gene-flow. PMID- 22066936 TI - Seasonal variations of insulin sensitivity from a euglycemic insulin clamp in elderly men. AB - INTRODUCTION: Seasonal variations in hemoglobin-A1c have been reported in diabetic patients, but the underlying mechanisms have not been elucidated. AIMS: To study if insulin sensitivity, insulin secretion, and fasting plasma glucose showed seasonal variations in a Swedish population-based cohort of elderly men. METHODS: Altogether 1117 men were investigated with a euglycemic insulin clamp and measurements of fasting plasma glucose and insulin secretion after an oral glucose tolerance test. Values were analyzed in linear regression models with an indicator variable for winter/summer season and outdoor temperature as predictors. RESULTS: During winter, insulin sensitivity (M/I, unit = 100 * mg * min(-1) * kg(-1)/(mU * L(-1))) was 11.0% lower (4.84 versus 5.44, P = 0.0003), incremental area under the insulin curve was 16.4% higher (1167 versus 1003 mU/L, P = 0.007). Fasting plasma glucose was, however, not statistically significantly different (5.80 versus 5.71 mmol/L, P = 0.28) compared to the summer season. There was an association between outdoor temperature and M/I (0.57 units increase (95% CI 0.29-0.82, P < 0.0001) per 10 degrees C increase of outdoor temperature) independent of winter/summer season. Adjustment for life-style factors, type 2 diabetes, and medication did not alter these results. CONCLUSIONS: Insulin sensitivity showed seasonal variations with lower values during the winter and higher during the summer season. Inverse compensatory variations of insulin secretion resulted in only minor variations of fasting plasma glucose. Insulin sensitivity was associated with outdoor temperature. These phenomena should be further investigated in diabetic patients. PMID- 22066937 TI - Does hormone therapy, tibolone or raloxifene modify VEGF expression in cervical epithelial cells? AB - AIM: Vascular endothelial growth factor (VEGF) seems to be a critical molecule in cervical carcinogenesis. We aimed to investigate the possible associations between hormonal factors and VEGF expression in cervical epithelial cells from postmenopausal women. METHOD: A total of 105 healthy postmenopausal women (aged 45-68 years old) attending a university menopause clinic were enrolled in this cross-sectional study. Pap smears were derived from current users of 17beta estradiol 1 mg + norethisterone acetate 0.5 mg (n = 28), tibolone 2.5 mg (n = 23), raloxifene HCl 60 mg (n = 21) and women not receiving treatment (n = 33). VEGF immunostaining was evaluated in squamous, glandular and metaplastic cells, using a semiquantitative method (rating scale: 0-3). RESULTS: Concerning endogenous hormones, higher Delta4-androstenedione levels were associated with more intense VEGF immunostaining in glandular (p = 0.041) and metaplastic cells (p = 0.004). Hormone therapy and raloxifene did not induce any changes in VEGF immunoreactivity in the examined cells. In contrast, tibolone administration was accompanied by diminished VEGF presence in metaplastic cells (p = 0.016 vs. controls). CONCLUSION: Our findings may in part reflect the molecular processes contributing to the safe profile of hormone therapy, tibolone and raloxifene in cervical carcinogenesis. PMID- 22066938 TI - Prospective study of erythema toxicum neonatorum: epidemiology and predisposing factors. AB - We performed a prospective study of 1,000 neonates investigated in the first 72 hours of life in the health area of Ferrol (northwest of Spain) to assess the prevalence of erythema toxicum neonatorum, the anatomical sites most frequently involved, the influence of different maternal and neonatal parameters, day of life of medical examination, and type of delivery (vaginal or Cesarean). Overall prevalence of erythema toxicum neonatorum was 16.7%. Lesions most frequently involved the trunk, buttocks, and proximal areas of limbs. A higher prevalence of this dermatosis was found in Caucasian newborns (p = 0.01) and those with higher birthweight (p < 0.05), greater gestational age (p < 0.05), vaginal delivery (p < 0.05), maternal age of <30 years (p = 0.28), and fewer than two previous pregnancies (p = 0.12). PMID- 22066939 TI - Extremes of an aromatase index predict increased 25-year risk of cardiovascular mortality in older women. AB - BACKGROUND: Peripheral conversion of androgens to oestrogens via aromatase is the primary source of oestrogen in postmenopausal women and may play a role in cardiovascular health. DESIGN: Prospective. PARTICIPANTS, MEASUREMENTS: The association of an index of aromatase activity (AROM), the serum oestrone-to androstenedione ratio, with 25-year cardiovascular disease (CVD) mortality was examined in 819 postmenopausal non-oestrogen using women (mean age at baseline = 72). RESULTS: Overall, 247 deaths were attributed to CVD. The median AROM value was 60 (95% range 17-129). AROM was positively correlated with age (r = 0.28) and body mass index (BMI) (r = 0.22) (P < 0.001). The age-adjusted risk for CVD mortality was significantly elevated for women in the lowest (HR = 2.01, 95% CI 1.31-3.12) and highest (HR = 1.51, 95%CI 1.02-2.22) quintiles of AROM, compared with the middle quintile. This U-shaped association persisted after additional adjustment for BMI, waist-to-hip ratio, exercise, smoking, alcohol use and traditional CVD risk factor covariates. There was a significant interaction of AROM and BMI (P = 0.001), such that high AROM was associated with a 63% reduction in risk of CVD death for women with low BMI (<22 kg/m(2) ), but with 2.1- to 2.5 fold increased risk in women with mid-range (22-<25 kg/m(2) ) and high (>=25 kg/m(2) ) BMI. Oestradiol did not influence AROM associations and was not independently related to CVD death. CONCLUSIONS: These results suggest that aromatase is a novel endocrine factor predictive of CVD mortality among postmenopausal women. If confirmed, additional studies are needed to determine whether extremes of aromatase reflect genetic influences or underlying disease processes. PMID- 22066940 TI - Molecular scale modeling of polymer imprint nanolithography. AB - We present the results of large-scale molecular dynamics simulations of two different nanolithographic processes, step-flash imprint lithography (SFIL), and hot embossing. We insert rigid stamps into an entangled bead-spring polymer melt above the glass transition temperature. After equilibration, the polymer is then hardened in one of two ways, depending on the specific process to be modeled. For SFIL, we cross-link the polymer chains by introducing bonds between neighboring beads. To model hot embossing, we instead cool the melt to below the glass transition temperature. We then study the ability of these methods to retain features by removing the stamps, both with a zero-stress removal process in which stamp atoms are instantaneously deleted from the system as well as a more physical process in which the stamp is pulled from the hardened polymer at fixed velocity. We find that it is necessary to coat the stamp with an antifriction coating to achieve clean removal of the stamp. We further find that a high density of cross-links is necessary for good feature retention in the SFIL process. The hot embossing process results in good feature retention at all length scales studied as long as coated, low surface energy stamps are used. PMID- 22066941 TI - Bingo! Externally supported performance intervention for deficient visual search in normal aging, Parkinson's disease, and Alzheimer's disease. AB - External support may improve task performance regardless of an individual's ability to compensate for cognitive deficits through internally generated mechanisms. We investigated if performance of a complex, familiar visual search task (the game of bingo) could be enhanced in groups with suboptimal vision by providing external support through manipulation of task stimuli. Participants were 19 younger adults, 14 individuals with probable Alzheimer's disease (AD), 13 AD-matched healthy adults, 17 non-demented individuals with Parkinson's disease (PD), and 20 PD-matched healthy adults. We varied stimulus contrast, size, and visual complexity during game play. The externally supported performance interventions of increased stimulus size and decreased complexity resulted in improvements in performance by all groups. AD also obtained benefit from increasing contrast, presumably by compensating for their contrast sensitivity deficit. The general finding of improved performance across healthy and afflicted groups suggests the value of visual support as an easy-to-apply intervention to enhance cognitive performance. PMID- 22066942 TI - Topological and electronic influences on magnetic exchange coupling in Fe(III) ethynylbenzene dendritic building blocks. AB - Significant variance in the magnitude of reported exchange coupling parameters (both experimental and computed) for paramagnetic transition metal-ethynylbenzene complexes suggests that nuances of the magnetostructural relationship in this class of compounds remain to be understood and controlled, toward maximizing the stability of high-spin ground states. We report the preparation, electrochemical behavior, magnetic properties, and results of computational investigations of a series of iron ethynylbenzene complexes with coordination environments suitable for metallodendrimer assembly: [(dmpe)(2)FeCl(C(2)Ph)](OTf) (1), [(dmpe)(4)Fe(2)Cl(2)(MU-p-DEB)](BAr(F)(4))(2) (2), [(dmpe)(6)Fe(3)Cl(3)(TEB)] (3), [(dmpe)(6)Fe(3)Cl(3)(MU(3)-TEB)](OTf)(3) (4), and [(dmpe)(4)Fe(2)Cl(2)(MU-m DEB)](BAr(F)(4))(2) (5) [dmpe = 1,2-bis(dimethylphosphino)ethane; p-H(2)DEB = 1,4 diethynylbenzene; BAr(F)(4) = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate; H(3)TEB = 1,3,5-triethynylbenzene; m-H(2)DEB = 1,3-diethynylbenzene]. As expected, the ligand topology drives the antiferromagnetic coupling in 2 (J = 134 cm(-1) using the H = -2JS(1).S(2) convention) and the ferromagnetic coupling in 4 and 5 (J = +37 cm(-1), J' = +5 cm(-1) for 4; J = +11 cm(-1) for 5); the coupling is comparable to but deviates significantly from values reported for related Cp*-containing species (Cp* = eta(5)-C(5)Me(5)). The origins of these differences are explored computationally: a density functional theory (DFT) approach for treating the coupling of three spin centers as a linear combination of single-determinantal descriptions is developed and described, and the results of these computations can be generalized to other paramagnetic systems. Unrestricted B3LYP hybrid DFT calculations performed on rotamers of 4 and 5 and related complexes, as well as Cp* analogues, provide J values that correlate with the experimental values. We find that geometric considerations dominate the magnetism of the Cp* complexes, while topology and alkynyl ligand electronics combine more subtly to drive the magnetism of the new complexes reported here. These calculations imply that substantial magnetic exchange parameters, with accompanying well-isolated high-spin ground states, are achievable for ethynylbenzene-bridged paramagnetic metallodendrimers. PMID- 22066944 TI - Denervation affects regenerative responses in MRL/MpJ and repair in C57BL/6 ear wounds. AB - The MRL/MpJ mouse displays the rare ability amongst mammals to heal injured ear tissue without scarring. Numerous studies have shown that the formation of a blastema-like structure leads to subsequent tissue regeneration in this model, indicating many parallels with amphibian limb regeneration and mammalian embryogenesis. We have recently shown that the MRL/MpJ mouse also possesses an enhanced capacity for peripheral nerve regeneration within the ear wound. Indeed, nerves are vital for the initial phase of blastema formation in the amphibian limb. In this study we investigated the capacity for wound regeneration in a denervated ear. The left ears of MRL/MpJ mice and C57BL/6 (a control strain known to have a poorer regenerative capacity) were surgically denervated at the base via an incision and nerve transection, immediately followed by a 2-mm ear punch wound. Immunohistochemical analysis showed a lack of neurofilament expression in the denervated ear wound. Histology revealed that denervation prevented blastema formation and chrondrogenesis, and also severely hindered normal healing, with disrupted re-epithelialisation, increasing wound size and progressive necrosis towards the ear tip. Denervation of the ear obliterated the regenerative capacity of the MRL/MpJ mouse, and also had a severe negative effect on the ear wound repair mechanisms of the C57BL/6 strain. These data suggest that innervation may be important not only for regeneration but also for normal wound repair processes. PMID- 22066945 TI - Light interception efficiency explained by two simple variables: a test using a diversity of small- to medium-sized woody plants. AB - * Plant light interception efficiency is a crucial determinant of carbon uptake by individual plants and by vegetation. Our aim was to identify whole-plant variables that summarize complex crown architecture, which can be used to predict light interception efficiency. * We gathered the largest database of digitized plants to date (1831 plants of 124 species), and estimated a measure of light interception efficiency with a detailed three-dimensional model. Light interception efficiency was defined as the ratio of the hemispherically averaged displayed to total leaf area. A simple model was developed that uses only two variables, crown density (the ratio of leaf area to total crown surface area) and leaf dispersion (a measure of the degree of aggregation of leaves). * The model explained 85% of variation in the observed light interception efficiency across the digitized plants. Both whole-plant variables varied across species, with differences in leaf dispersion related to leaf size. Within species, light interception efficiency decreased with total leaf number. This was a result of changes in leaf dispersion, while crown density remained constant. * These results provide the basis for a more general understanding of the role of plant architecture in determining the efficiency of light harvesting. PMID- 22066946 TI - First prescription of new elderly patients attending the psychiatry outpatient of a tertiary care institute in North India. AB - AIM: There is lack of data on prescription patterns in elderly patients from developing countries. The aim of this study is to examine the first prescription given to elderly patients (age >60 years) attending the psychiatry outpatient clinic of a tertiary care hospital. METHODS: In this retrospective study, data on patients older than 60 years attending the psychiatric outpatient clinic of a tertiary care hospital between 1 January 2009 and 30 November 2010 were extracted from the computer-based registry and analyzed. RESULTS: During the study period, 1192 new patients older than and equal to 60 years registered with the psychiatric outpatient clinic. Exact prescription data was available for 975 patients. The most common major diagnostic group was mood disorders (33.9%), followed by neurotic, stress-related and somatoform disorders (23.1%). Across all diagnostic groups, olanzapine was the most commonly prescribed antipsychotic medication (20.7% of patients with an organic mental disorder, 40.8% with psychotic disorder, 30.2% with bipolar disorder); quetiapine and risperidone were the other commonly prescribed antipsychotics. Across all diagnostic groups, escitalopram was the most commonly prescribed antidepressant, and sertraline was the second most frequently prescribed SSRI. Among mood stabilizers, valproate was preferred over lithium (25.4% vs.12.7%). Sedative-hypnotic medications were frequently prescribed across all diagnostic groups. Clonazepam and lorazepam were the most often prescribed benzodiazepines. The mean number of psychotropic medications was highest among bipolar disorder patients (1.84) and least among the patients with an organic mental disorder (1.25). CONCLUSIONS: Olanzapine, SSRI and clonazepam were the most commonly prescribed antipsychotic, antidepressant, and benzodiazepine, respectively, and valproate was preferred over lithium among elderly patients with bipolar disorder. PMID- 22066948 TI - Enrichment of sulfate-reducing bacteria and resulting mineral formation in media mimicking pore water metal ion concentrations and pH conditions of acidic pit lakes. AB - Acid mine drainage sites are extreme environments with high acidity and metal ion concentrations. Under anoxic conditions, microbial sulfate reduction may trigger the formation of secondary minerals as a result of H2S production and pH increase. This process was studied in batch experiments with enrichment cultures from acidic sediments of a pit lake using growth media set at different pH values and containing elevated concentrations of Fe2+ and Al3+. At initial pH values of 5 and 6, sulfate reduction occurred shortly after inoculation. Sulfate- reducing bacteria affiliated to the genus Desulfosporosinus predominated the microbial communities as shown by 16S rRNA gene analysis performed at the end of the incubation. At initial pH values of 3 and 4, sulfate reduction and cell growth occurred only after an extended lag phase, however, at a higher rate than in the less acidic assays. At the end of the growth phase, enrichments were dominated by Thermodesulfobium spp. suggesting that these sulfate reducers were better adapted to acidic conditions. Iron sulfides in the bulk phase were common in all assays, but specific aluminum precipitates formed in close association with cell surfaces and may function as a detoxification mechanism of dissolved Al species at low pH. PMID- 22066949 TI - Effect of JPEG compression on the diagnostic accuracy of periapical images in the detection of root fracture. AB - The ability of a periapical radiograph to exhibit the fracture depends on many factors including, but not limited to, the resolution of the image. The quality can be reduced by the image compression. The purpose of this study is to evaluate the effect of Joint Photographic Experts Group (JPEG) compressions on the diagnostic capability of periapical images in the detection of root fractures. Ten dry human mandibles containing 151 teeth were used in this study. Mandibles were radiographed with direct digital imaging sensor using the paralleling technique. Four observers detected root fracture on the images saved in one uncompressed and two compressed formats. Receiver operating characteristic (ROC) and anova analyses were performed to compare the performance of the three different systems and evaluate the effect of the compression on the accuracy of root fracture detection. Results did not show any statistically significant difference between the original, large images presented in tagged image file format (TIFF) and the two compressed images (JPEG medium file and JPEG small file images) in the detection of root fractures. The intra-rater comparison showed a significant consistency in the detection of the fracture. The compression reduced the file size considerably (from 1.77 MB to 453 and 95 Kb), but it did not affect the accuracy of root fracture detection. The file size reduction, on the other hand, is very beneficial for image electronic storage and mainly in teleradiology. PMID- 22066947 TI - Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension. AB - Severe pulmonary hypertension (PH) associated with vascular remodeling is a long term complication of HIV infection (HIV-PH) affecting 1/200 infected individuals vs. 1/200,000 frequency in the uninfected population. Factors accounting for increased PH susceptibility in HIV-infected individuals are unknown. Rhesus macaques infected with chimeric SHIVnef virions but not with SIV display PH-like pulmonary vascular remodeling suggesting that HIV-Nef is associated with PH; these monkeys showed changes in nef sequences that correlated with pathogenesis after passage in vivo. We further examined whether HIV-nef alleles in HIV-PH subjects have signature sequences associated with the disease phenotype. We evaluated specimens from participants with and without HIV-PH from European Registries and validated results with samples collected as part of the Lung-HIV Studies in San Francisco. We found that 10 polymorphisms in nef were overrepresented in blood cells or lung tissue specimens from European HIV-PH individuals but significantly less frequent in HIV-infected individuals without PH. These polymorphisms mapped to known functional domains in Nef. In the validation cohort, 7/10 polymorphisms in the HIV-nef gene were confirmed; these polymorphisms arose independently from viral load, CD4(+) T cell counts, length of infection, and antiretroviral therapy status. Two out of 10 polymorphisms were previously reported in macaques with PH-like pulmonary vascular remodeling. Cloned recombinant Nef proteins from clinical samples down-regulated CD4, suggesting that these primary isolates are functional. This study offers new insights into the association between Nef polymorphisms in functional domains and the HIV-PH phenotype. The utility of these polymorphisms as predictors of PH should be examined in a larger population. PMID- 22066957 TI - An activation domain of plasmid R1 TraI protein delineates stages of gene transfer initiation. AB - Bacterial conjugation is a form of type IV secretion that transports protein and DNA to recipient cells. Specific bacteriophage exploit the conjugative pili and cell envelope spanning protein machinery of these systems to invade bacterial cells. Infection by phage R17 requires F-like pili and coupling protein TraD, which gates the cytoplasmic entrance of the secretion channel. Here we investigate the role of TraD in R17 nucleoprotein uptake and find parallels to secretion mechanisms. The relaxosome of IncFII plasmid R1 is required. A ternary complex of plasmid oriT, TraD and a novel activation domain within the N-terminal 992 residues of TraI contributes a key mechanism involving relaxase-associated properties of TraI, protein interaction and the TraD ATPase. Helicase-associated activities of TraI are dispensable. These findings distinguish for the first time specific protein domains and complexes that process extracellular signals into distinct activation stages in the type IV initiation pathway. The study also provided insights into the evolutionary interplay of phage and the plasmids they exploit. Related plasmid F adapted to R17 independently of TraI. It follows that selection for phage resistance drives not only variation in TraA pilins but diversifies TraD and its binding partners in a plasmid-specific manner. PMID- 22066958 TI - Isolates of Thermoanaerobacter thermohydrosulfuricus from decaying wood compost display genetic and phenotypic microdiversity. AB - In this study, 12 strains of Thermoanaerobacter were isolated from a single decaying wood compost sample and subjected to genetic and phenotypic profiling. The 16S rRNA encoding gene sequences suggested that the isolates were most similar to strains of either Thermoanaerobacter pseudethanolicus or Thermoanaerobacter thermohydrosulfuricus. Examination of the lesser conserved chaperonin-60 (cpn60) universal target showed that some isolates shared the highest sequence identity with T. thermohydrosulfuricus; however, others to Thermoanaerobacter wiegelii and Thermoanaerobacter sp. Rt8.G4 (formerly Thermoanaerobacter brockii Rt8.G4). BOX-PCR fingerprinting profiles identified differences in the banding patterns not only between the isolates and the reference strains, but also among the isolates themselves. To evaluate the extent these genetic differences were manifested phenotypically, the utilization patterns of 30 carbon substrates were examined and the niche overlap indices (NOI) calculated. Despite showing a high NOI (> 0.9), significant differences existed in the substrate utilization capabilities of the isolates suggesting that either a high degree of niche specialization or mechanisms allowing for non competitive co-existence, were present within this ecological context. Growth studies showed that the isolates were physiologically distinct in both growth rate and the fermentation product ratios. Our data indicate that phenotypic diversity exists within genetically microdiverse Thermoanaerobacter isolates from a common environment. PMID- 22066959 TI - Myocardial systolic velocities and deformation assessed by speckle tracking for early detection of left ventricular dysfunction in asymptomatic patients with severe primary mitral regurgitation. AB - AIMS: In asymptomatic patients with severe primary mitral regurgitation (PMR), early detection of left ventricular (LV) dysfunction indicates the optimal timing of mitral valve surgery; however, normal ejection fraction (EF) and end-systolic diameter (ESD) can mask significant LV impairment. METHODS: We studied 28 asymptomatic patients (59 +/- 13 years, 18 male) with severe PMR, EF > 60%, and ESD < 45 mm, and 10 age-matched healthy subjects. All underwent echocardiography with tissue velocity imaging to assess LV geometry, EF, and longitudinal systolic function; and two-dimensional speckle tracking to assess longitudinal strain (LS) and longitudinal strain rate (LSR), and radial strain (RS) and radial strain rate (RSR). Patients were reevaluated 14 days after successful mitral valve repair and divided in: IA, with a postoperative EF reduction >10% (13 patients) and IB, with an EF reduction <10% (15 patients). RESULTS: Patients with PMR had longitudinal dysfunction and decreased radial systolic deformation, by comparison with controls, although EF and ESD were similar. Subgroup IA had significantly lower S(TVI) , LS, and RS than IB (7.3 +/- 0.9 vs 10.8 +/- 1.5 m/s; -16.0 +/- 4.2% vs 21.7 +/- 2.1%; and 37.4 +/- 2.5% vs 41.6 +/- 2.4%; all p < 0.001) although preoperative LV mass index, LV diameters, and EF were similar. Multiple stepwise regression analysis showed that S(TVI) and the combination of S(TVI) and LS represent the main independent predictors for a postoperative EF reduction >10% (r(2) = 0.52, p < 0.001; and r(2) = 0.70, p < 0.001, respectively). CONCLUSION: Myocardial systolic velocities as well as radial and longitudinal LV deformation assessed by speckle tracking can detect subclinical LV dysfunction and predict impaired postoperative LV function in asymptomatic patients with severe PMR. PMID- 22066960 TI - Susceptibility to and resistance determinants of fusidic acid in Staphylococcus aureus isolated from Chinese children with skin and soft tissue infections. AB - This study aims to determine the resistance rates and determinants of fusidic acid among Staphylococcus aureus isolates collected from Chinese pediatric patients with skin and soft tissue infections (SSTIs). Between 2008 and 2009, a total of 186 clinical S. aureus isolates were collected from the pediatric patients with SSTIs, abscess (44.6%) was the most common SSTI in children 0-16 years old. Four clinical isolates (4/186, 2.2%) were resistant to fusidic acid. Two of these isolates were methicillin-resistant S. aureus (MRSA) that carry the fusC gene. The other two isolates were methicillin-sensitive S. aureus (MSSA) that carry the fusB gene. In the two fusB-positive clinical isolates, the fusB gene was located in a transposon-like element that has 99% identity with a pUB101 fragment from S. aureus. The four fusidic acid-resistant clinical isolates were ST1-MRSA-SCCmecV-t127, ST93-MRSA-SCCmecIII-t202, ST680-MSSA-t5415, and ST680-MSSA t377. The fusidic acid resistance rate of S. aureus isolated from Chinese pediatric patients with SSTIs was low, and the genes fusB and fusC were the main resistance determinants. The transposon-like element that contains the fusB gene might participate in the transmission of fusidic acid resistance genes. This is the first report regarding the emergence of fusidic acid-resistant clinical S. aureus isolates in mainland China. PMID- 22066961 TI - A prospective, multi-centre, randomised, open label, parallel, comparative study to evaluate effects of AQUACEL(r) Ag and Urgotul(r) Silver dressing on healing of chronic venous leg ulcers. AB - This study compared wound healing efficacy of two silver dressings, AQUACEL((r)) Ag and Urgotul((r)) Silver, against venous ulcers at risk of infection, over 8 weeks of treatment. The primary objective was to show non inferiority of AQUACEL((r)) Ag to Urgotul((r)) Silver. Patients (281) were randomised into two groups. The AQUACEL((r)) Ag group had 145 patients treated with AQUACEL((r)) Ag for 4 weeks followed by AQUACEL for another 4 weeks. TheUrgotul((r)) Silver group had 136 patients treated with Urgotul((r)) Silver for 4 weeks followed by Urgotul((r)) for another 4 weeks. In both groups, ulcer size and depth, safety events and ulcer healing were compared. After 8 weeks of treatment, the AQUACEL((r)) Ag group had a relative wound size reduction (49.65% +/- 52.53%) compared with the Urgotul((r)) Silver group (42.81% +/- 60.0%). The non inferiority of the AQUACEL((r)) Ag group to the Urgotul((r)) Silver group was established based on the difference between them (6.84% +/- 56.3%, 95% confidence interval -6.56 to 20.2) and the pre-defined non inferiority margin (-15%). Composite wound healing analysis showed that the AQUACEL((r)) Ag group had statistically higher percentage of subjects with better wound progression (66.9% versus 51.9%, P = 0.0108). In general, both dressings were effective at promoting healing of venous ulcers. PMID- 22066966 TI - Highly efficient synthesis of quinoxalinone-N-oxide via tandem nitrosation/aerobic oxidative C-N bond formation. AB - An efficient method for constructing quinoxalinone-N-oxides from cyanoacetanilides has been developed. This transformation can be achieved using inexpensive reagents and molecular oxygen under mild conditions, thus offering a practical pathway to quinoxalinone-containing pharmaceuticals such as ataquimast and opaviraline. PMID- 22066968 TI - Phylogeographic analyses of the southern leopard frog: the impact of geography and climate on the distribution of genetic lineages vs. subspecies. AB - The southeastern United States is a major phylogeographic break hotspot for amphibians, but the processes underlying this hotspot remain to be explicitly tested. We test the correlation of genetic lineages with subspecies breaks in the southeastern United States and the association of such breaks with climate, using Rana sphenocephala as a case study, and place our results in the broader context of the Alabama-Appalachian suture zone (AL-Appalachian SZ). We use genetic and ecological methods to (i) determine whether genetic lineages are coincident with the AL-Appalachian SZ or the subspecies and (ii) test the correlation of major climatic breaks with genetic structure and morphological variation in R. sphenocephala. Bayesian phylogenetic analyses of the ND1 mtDNA gene and microsatellite cluster analyses revealed two distinct lineages with over 4% sequence divergence. The geographic distributions of the two lineages are concordant with the AL-Appalachian SZ but do not correspond to the ranges of the subspecies based on morphology. Mantel tests revealed that isolation by distance and historical barriers to gene flow, rather than climate, are the major drivers of genetic divergence at neutral loci. Examination of climate breaks across the Southeast revealed a pattern incongruent with suture zone hotspots, suggesting that phylogenetic structure has been driven primarily by historical factors, such as isolation, the Appalachian Mountains and the Apalachicola/Chattahoochee/Flint River Basin. However, climate breaks are consistent with the geographic distribution of the subspecies of R. sphenocephala, suggesting that environmental pressures may be driving divergence in morphological traits that outpaces molecular evolution. PMID- 22066969 TI - Maxillary sinus floor elevation using a tissue-engineered bone with calcium magnesium phosphate cement and bone marrow stromal cells in rabbits. AB - The objective of this study was to assess the effects of maxillary sinus floor elevation with a tissue-engineered bone constructed with bone marrow stromal cells (bMSCs) and calcium-magnesium phosphate cement (CMPC) material. The calcium (Ca), magnesium (Mg), and phosphorus (P) ions released from calcium phosphate cement (CPC), magnesium phosphate cement (MPC), and CMPC were detected by inductively coupled plasma atomic emission spectroscopy (ICP-AES), and the proliferation and osteogenic differentiation of bMSCs seeded on CPC, MPC, and CMPC or cultured in CPC, MPC, and CMPC extracts were measured by MTT analysis, alkaline phosphatase (ALP) activity assay, alizarin red mineralization assay, and real-time PCR analysis of the osteogenic genes ALP and osteocalcin (OCN). Finally, bMSCs were combined with CPC, MPC, and CMPC and used for maxillary sinus floor elevation in rabbits, while CPC, MPC, or CMPC without cells served as control groups. The new bone formation in each group was detected by histological finding and fluorochrome labeling at weeks 2 and 8 after surgical operation. It was observed that the Ca ion concentrations of the CMPC and CPC scaffolds was significantly higher than that of the MPC scaffold, while the Mg ions concentration of CMPC and MPC was significantly higher than that of CPC. The bMSCs seeded on CMPC and MPC or cultured in their extracts proliferated more quickly than the cells seeded on CPC or cultured in its extract, respectively. The osteogenic differentiation of bMSCs seeded on CMPC and CPC or cultured in the corresponding extracts was significantly enhanced compared to that of bMSCs seeded on MPC or cultured in its extract; however, there was no significant difference between CMPC and CPC. As for maxillary sinus floor elevation in vivo, CMPC could promote more new bone formation and mineralization compared to CPC and MPC, while the addition of bMSCs could further enhance its new bone formation ability significantly. Our data suggest that CMPC possesses moderate biodegradability and excellent osteoconductivity, which may be attributed to its Ca and Mg ion composition, and the tissue-engineered bone constructed of CMPC and bMSCs might be a potential alterative graft for maxillofacial bone regeneration. PMID- 22066970 TI - What can we learn from studies on regional differences in the utilization of laboratory tests? PMID- 22066971 TI - The type I interferon system in the etiopathogenesis of autoimmune diseases. AB - Many patients with systemic autoimmune diseases have signs of a continuous production of type I interferon (IFN) and display an increased expression of IFN alpha-regulated genes. The reason for the on-going IFN-alpha synthesis in these patients seems to be an activation of plasmacytoid dendritic cells (pDCs) by immune complexes (ICs), consisting of autoantibodies in combination with DNA or RNA-containing autoantigens. Such interferogenic ICs are internalized via the FcgammaRIIa expressed on pDCs, reach the endosome, and stimulate Toll-like receptor (TLR)-7 or -9, which subsequently leads to IFN-alpha gene transcription. Variants of genes involved in both the IFN-alpha synthesis and response have been linked to an increased risk to develop systemic lupus erythematosus (SLE) and other autoimmune diseases. Among these autoimmunity risk genes are IFN regulatory factor 5 (IRF5), which is involved in TLR signaling, and the signal transducer and activator of transcription 4 (STAT4) that interacts with the type I IFN receptor. Several other gene variants in the IFN signaling pathway also confer an increased risk to develop an autoimmune disease. The observations that IFN-alpha therapy can induce autoimmunity and that many autoimmune conditions have an on going type I IFN production suggest that the type I IFN system has a pivotal role in the etiopathogenesis of these diseases. Possible mechanisms behind the dysregulated type IFNsystem in autoimmune diseases and how the IFN-alpha produced can contribute to the development of an autoimmune process will be reviewed. PMID- 22066972 TI - Regional variations in test requiring patterns of general practitioners in Spain. AB - OBJECTIVE: To analyze the requesting patterns for a range of laboratory tests ordered in 2009 from eight laboratories providing services to eight health areas, using appropriate indicators. DESIGN: Indicators measured every test request per 1,000 inhabitants, and indicators that measured the number of tests per related test requested by general practitioners were calculated. The savings generated, if each Health Care Department achieved the appropriate indicator standard, were also calculated. Laboratory Information System registers were collected, and indicators were calculated automatically in each laboratory using a data warehouse application. RESULTS: There was a large difference in demand for tests by health areas. The ratio of related tests also showed a great variability. The savings generated if each Health Care Department had achieved the appropriate indicator standard were ?172,116 for free thyroxine, ?18,289 for aspartate aminotransferase, and ?62,678 for urea. CONCLUSIONS: Considerable variability exists in general practitioners' demand for laboratory tests. PMID- 22066973 TI - Comparison of epidural tramadol-ropivacaine and fentanyl-ropivacaine for labor analgesia: a prospective randomized study. AB - BACKGROUND: To test the hypothesis that 5 mg/mL tramadol is superior to 3 ?g/mL fentanyl when combined with 0.125% ropivacaine in parturients undergoing labor during epidural analgesia. METHODS: Sixty-one parturients undergoing labor selected for delivery with epidural analgesia were randomized into two groups: Group tramadol (0.125% ropivacaine plus tramadol 5 mg/mL) and Group fentanyl (0.125% ropivacaine plus fentanyl 3 ug/mL). Hemodynamics, rate of cesarean delivery, sensory block level, Bromage motor scale scores, instrument-assisted delivery, oxytocin use, visual analog scale (VAS) scores, Apgar scores, umbilical cord artery gas analysis, and maternal side-effects including nausea, vomiting, pruritus, urinary retention, shivering, hypotension, and respiratory depression were recorded. RESULTS: The two groups had no significant differences with respect to maternal hemodynamics, neonatal heart rate, VAS scores, rate of cesarean delivery, sensory block level, Bromage motor scale scores, instrument assisted delivery, oxytocin use, hypotension, nausea, vomiting, and respiratory depression (p > 0.05). The incidence of pruritus, shivering, and urinary retention were more commonly observed in Group fentanyl despite there was no significant difference between the two groups. Umbilical artery pH was significantly lower while PCO(2) was higher in Group fentanyl than Group tramadol (p = 0.003 and p = 0.026, respectively). Birth-weight, umbilical artery PO(2) and base deficit, and Apgar scores at 1 and 5 min were comparable between the two groups (p > 0.05). CONCLUSIONS: Our observations suggest that tramadol seems to be a safe alternative to fentanyl for labor analgesia due to its similar analgesic efficacy. PMID- 22066974 TI - Several sources of error in estimation of left ventricular mass with M-mode echocardiography in elderly subjects. AB - INTRODUCTION: M-mode echocardiography estimates of the left ventricular mass (LVM) were greater than magnetic resonance imaging (MRI) estimates. There are substantial differences between the methods both in the means of measuring and the calculation formula. The aim of this study was to investigate whether any difference in estimates of LVM between M-mode echocardiography and MRI is due to the means of measuring or to the calculation formula, using MRI as the gold standard. MATERIAL AND METHODS: M-mode echocardiography and MRI were performed on 229 randomly selected 70-year-old community-living subjects. LVM was calculated from echocardiography (LVM(echo)) and from MRI (LVM(MRI)) measurements using standard techniques. Additionally LVM was calculated with the echocardiography formula from echo-mimicking measurements made on MR images (LVM(MRI/ASE)). RESULTS: There were significant differences between all three LVM estimates in women, in men, and in the entire population. Echocardiography estimated LVM to be larger than did MRI, and the LVM(MRI/ASE) estimate was larger than the LVM(MRI). The difference between LVM(MRI) and LVM(MRI/ASE) was larger than the difference between LVM(echo) and LVM(MRI/ASE). There was a low correlation between LVM(echo) and LVM(MRI) (R(2) = 0.46) as well as between LVM(MRI/ASE) and LVM(MRI) (R(2) = 0.65). CONCLUSION: The means of measuring and the calculation formula both independently add to the error in LVM estimation with M-mode echocardiography. The error of the calculation formula seems to be greater than the error of the means of measuring in a population of community-living elderly men and women. PMID- 22066975 TI - A randomized controlled trial of exercise versus wait-list in chronic tennis elbow (lateral epicondylosis). AB - BACKGROUND: Chronic tennis elbow (lateral epicondylosis) is a common disorder. Like other chronic soft-tissue pain conditions it is often difficult to treat successfully. The effects of exercise have been discussed, but no convincing evidence has been put forward so far, and a simple protocol for exercise is lacking. AIMS OF THE STUDY: This study is a randomized, controlled, clinical trial of the effect of exercise versus expectation (wait-list) on pain, muscle strength, function, and quality of life in patients with long-standing lateral epicondylosis. METHODS: Eighty-one subjects with tennis elbow lasting for more than 3 months were randomly allocated to an exercise group (n = 40) or a reference group (n = 41). The exercise group performed daily exercise, with weekly load increase, for 3 months. The reference group was wait-listed, but otherwise followed in the same way. Outcome measures were pain during maximum voluntary muscle contraction (Cozen's test) and pain during maximum muscle elongation with a load (modified Empty-can-test); muscle strength was measured with a Chatillon MSE 100 hand-held dynamometer, and the Disability of the Arm, Shoulder and Hand (DASH) and the Gothenburg Quality of Life questionnaires. RESULTS: The exercise group had greater and faster regression of pain, both during muscle contraction and muscle elongation, than the reference group (p = 0.0005 and p = 0.0016, respectively). There was a non-significant muscle strength difference between the groups, but no differences regarding DASH scores or quality of life measures. CONCLUSIONS: Exercise appears to be superior to expectation in reducing pain in chronic lateral epicondylosis. PMID- 22066976 TI - A case report of multidisciplinary treatment of an adult patient with bilateral cleft lip and palate. AB - This is a case report about the successful orthodontic treatment of a bilateral cleft lip and palate patient by using a combination of bone grafting and subsequent prosthodontic rehabilitation. An adult patient with a bilateral cleft lip and palate presented with a concave profile, anterior and lateral crossbite, a markedly deep overbite, and residual bilateral alveolar clefts. His jaw movement patterns were unstable and irregular due to his collapsed bite. Orthodontic treatment with bilateral bone grafting improved his concave profile by downward and backward rotation of the mandible within the freeway space, and optimum occlusion and functionally stable and smooth jaw movements were obtained. After a 6-year retention period, no skeletal relapse could be detected, and his occlusal stability was satisfactory. PMID- 22066977 TI - Lupus erythematosus panniculitis in children: report of three cases and review of previously reported cases. AB - Lupus erythematosus panniculitis (LEP) is a rare finding in children, with only 12 fully reported prior cases in the English literature. We describe three cases of LEP in children younger than 18 and compare them to previous cases reported in the literature. We examine laboratory tests performed, biopsy results, age at onset and diagnosis, presence or absence of systemic symptoms, and outcomes after treatment. It is unknown what the risk is of these patients developing future systemic lupus erythematosus. We also discuss the relevance of subcutaneous panniculitis-like T-cell lymphoma, because the clinical and pathologic pictures are similar in presentation. PMID- 22066978 TI - Comparison of cytokine levels from undiluted vitreous of untreated patients with retinal vein occlusion. AB - PURPOSE: To compare cytokines in undiluted vitreous of treatment-naive patients with macular oedema without vitreomacular traction secondary to branch (BRVO), central (CRVO) and hemi-central (H-CRVO) retinal vein occlusion. METHODS: Ninety four patients (median age 72 years, 42 men) underwent an intravitreal combination therapy, including a single-site 23-gauge core vitrectomy and the application of bevacizumab and dexamethasone due to vision-decreasing macular oedema. Among these were 43 patients with BRVO, 35 with CRVO and 16 patients with hemi-CRVO, which were distributed in a fresh or old retinal vein occlusion type (seven or more months after onset). Undiluted vitreous samples were analysed for interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF-A) with cytometric BEAD assay. Vitreous samples from patients with idiopathic epiretinal membrane served as controls (n = 14). RESULTS: The mean cytokine values were highest in the CRVO group with IL-6 = 64.7 pg/ml (SD +/- 115.8), MCP-1 = 1015.8 pg/ml (+/-970.1) and VEGF-A = 278.4 pg/ml (+/-512.8), followed by the H-CRVO group with IL-6 = 59.9 pg/ml (SD +/- 97.5), MCP-1 = 938.8 pg/ml (+/-561.1) and VEGF-A = 211.5 pg/ml (+/-232.4). The BRVO group had IL-6 = 23.2 pg/ml (SD +/- 48.8), MCP-1 = 602.6 g/ml (+/-490.3) and VEGF A = 161.8 pg/ml (+/-314.4). The values of MCP-1 and VEGF-A were significantly different for CRVO or H-CRVO versus BRVO. All values were significantly higher than in the control samples, which had 6.2 +/- 3.4 pg/ml (IL-6), 253 +/- 74 pg/ml (MCP-1) and 7 +/- 4.9 pg/ml (VEGF-A). Within the old RVO type, only MCP-1 was significantly different for CRVO or H-CRVO versus BRVO. CONCLUSIONS: Both inflammatory markers and VEGF-A were higher in CRVO and H-CRVO than in BRVO undiluted vitreous samples. It seems that monocyte recruitment to the vessel wall, which might underlie the importance of eosinophils in tissue remodelling after RVO, is of special interest owing to the significant difference in MCP-1 in the older RVO types. PMID- 22066979 TI - Regulating the size and stabilization of lipid raft-like domains and using calcium ions as their probe. AB - We apply a means to probe, stabilize, and control the size of lipid raft-like domains in vitro. In biomembranes the size of lipid rafts is ca. 10-30 nm. In vitro, mixing saturated and unsaturated lipids results in microdomains, which are unstable and coalesce. This inconsistency is puzzling. It has been hypothesized that biological line-active surfactants reduce the line tension between saturated and unsaturated lipids and stabilize small domains in vivo. Using solution X-ray scattering, we studied the structure of binary and ternary lipid mixtures in the presence of calcium ions. Three lipids were used: saturated, unsaturated, and a hybrid (1-saturated-2-unsaturated) lipid that is predominant in the phospholipids of cellular membranes. Only membranes composed of the saturated lipid can adsorb calcium ions, become charged, and therefore considerably swell. The selective calcium affinity was used to show that binary mixtures, containing the saturated lipid, phase separated into large-scale domains. Our data suggests that by introducing the hybrid lipid to a mixture of the saturated and unsaturated lipids, the size of the domains decreased with the concentration of the hybrid lipid, until the three lipids could completely mix. We attribute this behavior to the tendency of the hybrid lipid to act as a line-active cosurfactant that can easily reside at the interface between the saturated and the unsaturated lipids and reduce the line tension between them. These findings are consistent with a recent theory and provide insight into the self-organization of lipid rafts, their stabilization, and size regulation in biomembranes. PMID- 22066980 TI - Maternal proviral load and vertical transmission of human T cell lymphotropic virus type 1 in Guinea-Bissau. AB - The relative importance of routes of transmission of human T cell lymphotropic virus type 1 (HTLV-1) in Guinea-Bissau is largely unknown; vertical transmission is thought to be important, but there are very few existing data. We aimed to examine factors associated with transmission in mothers and children in Guinea Bissau, where HTLV-1 is endemic (prevalence of 5% in the adult population). A cross-sectional survey was performed among mothers and their children (aged <15 years) in a rural community in Guinea-Bissau. A questionnaire to identify risk factors for infection and a blood sample were obtained. HTLV-1 proviral load in peripheral blood was determined and PCR was performed to compare long terminal repeat (LTR) sequences in mother-child pairs. Fourteen out of 55 children (25%) of 31 HTLV-1-infected mothers were infected versus none of 70 children of 30 uninfected mothers. The only factor significantly associated with HTLV-1 infection in the child was the proviral load of the mother; the risk of infection increased significantly with the log(10) proviral load in the mother's peripheral blood (OR 5.5, 95% CI 2.1-14.6, per quartile), adjusted for weaning age and maternal income. HTLV-1 sequences of the LTR region obtained from mother-child pairs were identical within pairs but differed between the pairs. Vertical transmission plays an important role in HTLV-1 transmission in this community in Guinea-Bissau. The risk of transmission increases with the mother's proviral load in the peripheral blood. Identical sequences in mother-child pairs give additional support to the maternal source of the children's infection. PMID- 22066981 TI - Predicting the size and properties of dendrimersomes from the lamellar structure of their amphiphilic Janus dendrimers. AB - Dendrimersomes are stable, monodisperse unilamellar vesicles self-assembled in water from amphiphilic Janus dendrimers. Their size, stability, and membrane structure are determined by the chemical structure of Janus dendrimer and the method of self-assembly. Comparative analysis of the periodic arrays in bulk and dendrimersomes assembled by ethanol injection in water of 11 libraries containing 108 Janus dendrimers is reported. Analysis in bulk and in water was performed by differential scanning calorimetry, X-ray diffraction, dynamic light scattering, and cryo-TEM. An inverse proportionality between size, stability, mechanical properties of dendrimersomes, and thickness of their membrane was discovered. This dependence was explained by the tendency of alkyl chains forming the hydrophobic part of the dendrimersome to produce the same local packing density regardless of the branching pattern from the hydrophobic part of the dendrimer. For the same hydrophobic alkyl chain length, the largest, toughest, and most stable dendrimersomes are those with the thinnest membrane that results from the interdigitation of the alkyl groups of the Janus dendrimer. A simplified spherical-shell model of the dendrimersome was used to demonstrate the direct correlation between the concentration of Janus dendrimer in water, c, and the size of self-assembled dendrimersome. This concentration-size dependence demonstrates that the mass of the vesicle membrane is proportional with c. A methodology to predict the size of the dendrimersome based on this correlation was developed. This methodology explains the inverse proportionality between the size of dendrimersome and its membrane thickness, and provides a good agreement between the experimental and predicted size of dendrimersome. PMID- 22066982 TI - High but not dry: diverse epiphytic bromeliad adaptations to exposure within a seasonally dry tropical forest community. AB - * Vascular epiphytes have developed distinct lifeforms to maximize water uptake and storage, particularly when delivered as pulses of precipitation, dewfall or fog. The seasonally dry forest of Chamela, Mexico, has a community of epiphytic bromeliads with Crassulacean acid metabolism showing diverse morphologies and stratification within the canopy. We hypothesize that niche differentiation may be related to the capacity to use fog and dew effectively to perform photosynthesis and to maintain water status. * Four Tillandsia species with either 'tank' or 'atmospheric' lifeforms were studied using seasonal field data and glasshouse experimentation, and compared on the basis of water use, leaf water delta(18) O, photosynthetic and morphological traits. * The atmospheric species, Tillandsia eistetteri, with narrow leaves and the lowest succulence, was restricted to the upper canopy, but displayed the widest range of physiological responses to pulses of precipitation and fog, and was a fog-catching 'nebulophyte'. The other atmospheric species, Tillandsia intermedia, was highly succulent, restricted to the lower canopy and with a narrower range of physiological responses. Both upper canopy tank species relied on tank water and stomatal closure to avoid desiccation. * Niche differentiation was related to capacity for water storage, dependence on fog or dewfall and physiological plasticity. PMID- 22066983 TI - PLS-DA - Docking Optimized Combined Energetic Terms (PLSDA-DOCET) protocol: a brief evaluation. AB - Docking studies have become popular approaches in drug design, where the binding energy of the ligand in the active site of the protein is estimated by a scoring function. Many promising techniques were developed to enhance the performance of scoring functions including the fusion of multiple scoring functions outcomes into a so-called consensus scoring function. Hereby, we evaluated the target oriented consensus technique using the energetic terms of several scoring functions. The approach was denoted PLSDA-DOCET. Optimization strategies for consensus energetic terms and scoring functions based on ROC metric were compared to classical rigid docking and to ligand-based similarity search methods comprising 2D fingerprints and ROCS. The ROCS results indicate large performance variations depending on the biological target. The AUC-based strategy of PLSDA DOCET outperformed the other docking approaches regarding simple retrieval and scaffold-hopping. The superior performance of PLSDA-DOCET protocol relative to single and combined scoring functions was validated on an external test set. We found a relative low mean correlation of the ranks of the chemotypes retrieved by the PLSDA-DOCET protocol and all the other methods employed here. PMID- 22066984 TI - Effect of milk renewal on human periodontal ligament fibroblast viability in vitro. AB - Milk has been studied extensively and has gained wide acceptance as a suitable storage medium capable of maintenance of avulsed teeth that cannot be replanted immediately. The objective of this study was to evaluate whether the renewal of milk as a storage medium every 24 h for up to 120 h is able to increase its ability to maintain human periodontal ligament fibroblasts (PDLF) viability in vitro. Plates with confluent PDLF were soaked in minimum essential medium (MEM) at 37 degrees C (positive control) and in skimmed milk (22 wells) and water (negative control) for 24, 48, 72, 96, and 120 h at 5 and 20 degrees C. The skimmed milk was renewed every 24 h in 11 of the wells of each plate. After these periods, cell viability was determined by the tetrazolium salt-based colorimetric (MTT) assay. Data were statistically analyzed by Kruskal-Wallis and Scheffe tests (alpha = 5%). At 24 h, milk and MEM performed similarly. However, from 48 h onwards, MEM was significantly better than renewed and not renewed milk at both temperatures. Regardless of temperature (5 or 20 degrees C), renewal of milk with fresh milk did not affect its ability to maintain PDLF viability. PMID- 22066985 TI - Cost-effectiveness of prasugrel in a US managed care population. AB - OBJECTIVE: Decision-makers in the US may be interested in the applicability to their populations of cost-effectiveness results generated from clinical trial populations. METHODS: An economic model estimating the cost-effectiveness of prasugrel plus aspirin relative to clopidogrel plus aspirin for patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) was developed from a managed care organization (MCO) perspective. The model estimated 15-month cardiovascular events or bleeding-related outcomes, life expectancy, and costs for patients who received thienopyridine treatment during and after a PCI following a diagnosis of ACS. Post-ACS event rates for patients treated with clopidogrel were from an MCO. The relative risks of these events with prasugrel compared with clopidogrel were from a head-to-head clinical trial. RESULTS: The results of the base-case analysis indicated that, in an MCO population, use of prasugrel-based therapy rather than clopidogrel-based therapy at current prices resulted in cost-savings and fewer clinical events over the 15 months after an ACS diagnosis followed by PCI. At possible lower prices for generic clopidogrel-based therapy, the cost-effectiveness ratio for prasugrel based therapy compared with clopidogrel-based therapy was between $6643 and $13,906 per life-year gained. The results were most sensitive to the relative costs of the two treatments and the cost for hospital stays. LIMITATIONS: Limitations of the study included lack of follow-up of patients disenrolling from the MCO before the end of the 15-month observation period, the assumption of equal relative risks of events in an MCO as in the clinical trial, and the lack of information on the ratio of cost to charges in the MCO database. CONCLUSIONS: Use of prasugrel-based therapy compared with clopidogrel-based therapy in ACS patients having a PCI resulted in cost-savings at current prices and favorable cost-effective ratios at likely generic prices for clopidogrel-based therapy because of offsetting savings in the costs of rehospitalization. PMID- 22066986 TI - Association of 29C>T polymorphism in the transforming growth factor-beta1 gene with lean body mass in community-dwelling Japanese population. AB - AIM: Sarcopenia is the significant degenerative loss of skeletal muscle mass and strength associated with aging, and it is one of the components of frailty. We previously reported an association between the 29C>T polymorphism in the transforming growth factor-beta1 gene (rs1800470) and the prevalence of vertebral fractures in subjects with postmenopausal osteoporosis. The association was not attributable to bone mineral density, which suggests that polymorphism influences some aspects of bone quality that affects strength and/or frailty rather than bone strength itself. Thus, we examined the relationship between genetic polymorphism and lean body mass in a Japanese population. METHODS: A total of 479 adults comprising 143 men and 336 women, age 23 to 85 years, participated in the present study. Fat-free mass was measured by dual energy X-ray absorptiometry, and the relative skeletal muscle index was calculated as the ratio of appendicular (sum of arms and legs) fat-free mass to the square of height. RESULTS: Total, leg, and appendicular fat-free mass as well as the relative skeletal muscle index were significantly lower in male subjects with CT/TT genotypes compared to those with CC genotype. Female subjects did not show any genotype-dependent differences when analyzed as a group, but when those without menstruation (postmenopausal women) were analyzed, arm fat-free mass was significantly lower in the CT/TT genotypes than in the CC genotype. CONCLUSIONS: T allele of the 29C>T polymorphism in the transforming growth factor-beta1 gene might be a risk factor of sarcopenia in a Japanese population. PMID- 22066987 TI - Effects of food ration on SMR: influence of food consumption on individual variation in metabolic rate in juvenile coho salmon (Onchorhynchus kisutch). AB - 1. Consistency of differences in standard metabolic rate (SMR) between individual juvenile salmonids and the apparently limited ability of individuals to regulate their SMR has led many researchers to conclude that differences in individual SMR are fixed (i.e. genetic). 2. To test for the effects of food ration on individual performance and metabolism, SMR was estimated by measuring oxygen consumption using flow-through respirometry on individually separated young of the year coho salmon (Oncorhynchus kisutch) placed on varying food rations over a period of 44 days. 3. Results demonstrate that the quantity of food consumed directly affects SMR of juvenile coho salmon, independent of specific dynamic action (SDA, an elevation in metabolic rate from the increased energy demands associated with digestion immediately following a meal) and indicates that higher food consumption is a cause of elevated SMR rather than a consequence of it. Juvenile coho salmon therefore demonstrated an ability to regulate their SMR according to food availability and ultimately food consumption. 4. This study indicates that food consumption may play a pivotal role in understanding individual variation in SMR independent of inherent genetic differences. We suggest that studies involving SMR need to be cautious about the effects of intra-individual differences in food consumption in communal tanks or in different microhabitats in the wild as disproportionate food consumption may contribute more to variation in SMR than intrinsic (genetic) factors. 5. In general, our results suggest that evolutionary changes in SMR are likely a response to selection on food consumption and growth, rather than SMR itself. PMID- 22066988 TI - Ciliate food vacuole content and bacterial community composition in the warm monomictic crater Lake Alchichica, Mexico. AB - To evaluate trophic relationships between ciliates and bacterioplankton during the stratification period in a lake, samples from three different layers [the upper part of the metalimnion (UM), the base of the metalimnion (BM) and the hypolimnion] were studied. The autotrophic picoplankton numbers, phylogenetic composition of heterotrophic picoplankton (HPP), and HPP composition in ciliates' food vacuoles were analyzed. Additionally, in situ incubations in dialysis bags were performed at the same selected depths to assess potential changes in picoplankton composition related to ciliates' feeding activity. Among the in situ HPP assemblage, no phylogenetic group dominated in the selected layers within the course of the study. The ciliate assemblage was dominated by scuticociliates, haptorids, and hypotrichs. Comparing ciliates' food vacuole content and in situ HPP composition, a high preference for Alphaproteobacteria was found at all three depths. Planctomycetes, and Delta- and Gammaproteobacteria were selected at BM and hypolimnion, respectively. However, selection of a given phylogenetic group in the time course of this study was observed only for Alphaproteobacteria in the UM. Similar trends were found in the incubations, but no relationship was found between the vacuole content of the ciliates and changes in HPP composition. PMID- 22066989 TI - Monoubiquitinated proteins decorate the Anaplasma phagocytophilum-occupied vacuolar membrane. AB - An emerging theme among vacuole-adapted bacterial pathogens is the ability to hijack ubiquitin machinery to modulate host cellular processes and secure pathogen survival. Mono- and polyubiquitination differentially dictate the subcellular localization, activity, and fate of protein substrates. Monoubiquitination directs membrane traffic from the plasma membrane to the endosome and has been shown to promote autophagy. Anaplasma phagocytophilum is an obligate intracellular bacterium that replicates within a host cell-derived vacuole that co-opts membrane traffic and numerous other host cell processes. Here, we show that monoubiquitinated proteins decorate the A. phagocytophilum occupied vacuolar membrane (AVM) during infection of promyelocytic HL-60 cell, endothelial RF/6A cells, and to a lesser extent, embryonic tick ISE6 cells. Monoubiquitinated proteins are present on the AVM upon its formation and continue to accumulate throughout infection. Tetracycline-mediated inhibition of de novo bacterial protein synthesis promotes the loss of ubiquitinated proteins from the AVM. This effect is reversible, as removal of tetracycline restores AVM ubiquitination to pretreatment levels. These results demonstrate a novel mechanism by which A. phagocytophilum remodels the composition of its host cell derived vacuolar membrane and present the first example of a Rickettsiales pathogen co-opting ubiquitin during intracellular residence. PMID- 22066998 TI - Localization and activity of the calcineurin catalytic and regulatory subunit complex at the septum is essential for hyphal elongation and proper septation in Aspergillus fumigatus. AB - Calcineurin, a heterodimer composed of the catalytic (CnaA) and regulatory (CnaB) subunits, plays key roles in growth, virulence and stress responses of fungi. To investigate the contribution of CnaA and CnaB to hyphal growth and septation, DeltacnaB and DeltacnaADeltacnaB strains of Aspergillus fumigatus were constructed. CnaA colocalizes to the contractile actin ring early during septation and remains at the centre of the mature septum. While CnaB's septal localization is CnaA-dependent, CnaA's septal localization is CnaB-independent, but CnaB is required for CnaA's function at the septum. Catalytic null mutations in CnaA caused stunted growth despite septal localization of the calcineurin complex, indicating the requirement of calcineurin activity at the septum. Compared to the DeltacnaA and DeltacnaB strains, the DeltacnaADeltacnaB strain displayed more defective growth and aberrant septation. While three Ca(2+) binding motifs in CnaB were sufficient for its association with CnaA at the septum, the amino-terminal arginine-rich domains (16-RRRR-19 and 44-RLRKR-48) are dispensable for septal localization, yet required for complete functionality. Mutation of the 51-KLDK-54 motif in CnaB causes its mislocalization from the septum to the nucleus, suggesting it is a nuclear export signal sequence. These findings confirm a cooperative role for the calcineurin complex in regulating hyphal growth and septation. PMID- 22066999 TI - Larval exposure to Francisella tularensis LVS affects fitness of the mosquito Culex quinquefasciatus. AB - Francisella tularensis is an environmental bacterium capable of infecting a wide spectrum of species from mammals and birds to reptiles. It has been demonstrated that F. tularensis can invade and survive within protozoa, but an association with aquatic insects has not been thoroughly investigated. We examined the interaction of F. tularensis LVS biofilms and Culex quinquefasciatus larvae to determine the effects on larvae and adults. Our results demonstrate that F. tularensis LVS can form and persist as biofilms in natural water and that the mosquito larvae of C. quinquefasciatus readily feed on biofilm and planktonic forms of F. tularensis LVS. Larvae raised in both bacteria-only cultures suffered significant delays in pupation. Adults resulting from larvae continuously exposed to the bacteria had significantly reduced wing lengths in males and fecundity of both sexes. The bacteria may be exerting these effects through localization and persistence within the midgut and Malpighian tubule cells of the larvae. The study of oral acquisition of pathogens by insect larvae can significantly contribute to the study of environmental persistence of pathogens. We show that oral uptake of F. tularensis LVS by C. quinquefasciatus larvae results in not only larval effects but also has effects on adult mosquitoes. These effects are important in understanding both the ecology of tularemia as well as bacterial interactions with aquatic invertebrates. PMID- 22067000 TI - No need for biopsies: comparison of three sample techniques for wound microbiota determination. AB - The aim of the study was to compare three sampling techniques used in routine diagnostics to identify the microbiota in chronic venous leg ulcers. A total of 46 patients with persisting venous leg ulcers were included in the study. At inclusion, swab, biopsy and filter paper pad samples were collected. After 4 weeks, additional biopsy and filter paper pad samples were collected. Bacteria were isolated and identified at species level by standard methods. The most common bacterial species detected was Staphylococcus aureus found in 89% of the ulcers. No methicillin-resistant S. aureus isolates were found. We did not find any significant differences regarding the bacterial species isolated between the three sampling techniques. However, using multiple techniques led to identification of more species. Our study suggests that it is sufficient to use swab specimens to identify the bacterial species present in chronic wounds, thus avoiding complications during and after biopsy sampling. PMID- 22067001 TI - Anti-c-Fms antibody inhibits lipopolysaccharide-induced osteoclastogenesis in vivo. AB - It has been reported that lipopolysaccharide (LPS) has the ability to induce inflammation and osteoclastogenesis. Osteoclast formation is dependent on macrophage-colony-stimulating factor (M-CSF) and ligand for the receptor activator of necrosis factor-kB. In this study, the effect of antibody against c Fms, which is the receptor of M-CSF, on LPS-mediated osteoclastogenesis was investigated in mice. LPS was administered with or without anti-c-Fms antibody into the supracalvaria of mice. The number of osteoclasts and the levels of mRNA for cathepsin K and tartrate-resistant acid phosphatase, which are osteoclast markers, in mice administered both LPS and anti-c-Fms antibody were lower than those in mice administered LPS alone. The level of tartrate-resistant acid phosphatase 5b as a marker of bone resorption in mice administered both LPS and anti-c-Fms antibody was also lower. Furthermore, the expression of the receptor activator of necrosis factor-kB, which is receptor activator of nuclear factor kappa-B ligand, was increased upon LPS administration, but the expression was inhibited by anti-c-Fms antibody. These results showed that anti-c-Fms antibody inhibits LPS-induced osteoclast formation. In conclusion, M-CSF and its receptor are potential therapeutic targets in bacterial infection-induced osteoclastogenesis, and anti-c-Fms antibody might be useful for inhibition of bacterial infection-induced bone destruction. PMID- 22067002 TI - Predictors for the development of severe tricuspid regurgitation with anatomically normal valve in patients with atrial fibrillation. AB - BACKGROUND AND AIMS: Atrial fibrillation (AF) may be a risk factor for severe functional tricuspid valve regurgitation (FTR). We aimed to determine the predictors of severe FTR in patients with AF. METHODS AND RESULTS: From our echocardiographic laboratory database, we searched for and reviewed the medical records of consecutive patients with severe FTR and AF seen at Mayo Clinic in Arizona from 2002 through 2009. Our search identified 42 patients who met all inclusion criteria. These patients (cases) with severe FTR and AF were compared with 38 patients (controls) with AF who had no greater than mild tricuspid regurgitation. Case patients with severe FTR were older than controls (mean, 81 years vs. 76 years; P < 0.001) and more frequently had chronic AF (69% vs 26%; P < 0.001). Mean right atrial volume (86 mL/m(2) vs 46 mL/m(2) ; P < 0.001), right ventricular volume (42 mL +/- 33 mL vs 22 mL +/-8 mL; P < 0.001) and tricuspid annular diameter (3.6 cm vs 3.0 cm; P < 0.001) were larger in cases than in controls. Patients with severe FTR also had a higher prevalence of right-sided heart failure (69% vs 16%; P < 0.001). After adjusting for age and gender, right atrial and right ventricular volumes were independent predictors for the development of severe FTR in patients with AF (odds ratio, 1.7 [95% CI, 1.3-2.8] for every 10 mL/m(2) increase in right atrial volume; P = 0.0002 and odds ratio, 3.1 [95% CI, 1.5-8.9] for every 10 mL increase in right ventricular volume; P = 0.0002). CONCLUSIONS: Severe FTR occurs in older patients with chronic AF as a result of marked right atrial and right ventricular dilatation; and enlargement of the tricuspid annulus in the absence of pulmonary hypertension. More importantly, severe FTR leads to increased prevalence of right-sided heart failure underscoring the nonbenign nature of chronic AF. PMID- 22067007 TI - A divergent and selective synthesis of isomeric benzoxazoles from a single N-Cl imine. AB - A divergent and regioselective synthesis of either 3-substituted benzisoxazoles or 2-substituted benzoxazoles from readily accessible ortho-hydroxyaryl N-H ketimines is described. The reaction proceeds in two distinct pathways through a common N-Cl imine intermediate: (a) N-O bond formation to form benzisoxazole under anhydrous conditions and (b) NaOCl mediated Beckmann-type rearrangement to form benzoxazole, respectively. The reaction path also depends on the electronic nature of the aromatic ring, with the electron-rich aromatic rings favoring the rearrangement and the electron-deficient rings favoring the N-O bond formation. A Beckmann-type rearrangement mechanism via net [1,2]-aryl migration for the formation of 2-substituted benzoxazole is proposed. PMID- 22067008 TI - A systematic review of issues around antenatal screening and prenatal diagnostic testing for genetic disorders: women of Asian origin in western countries. AB - Antenatal screening has become standard practice in many countries. However, not all pregnant women choose to be tested. In the UK, the incidence of some birth defects is found to be higher in babies of Asian women than in those of women from other ethnic groups, while there is some evidence suggesting that ethnic minorities, especially Asian women, are less likely to undergo antenatal screening and prenatal diagnosis, the reasons for which are unclear. This study aims to identify and describe the literature on issues around antenatal screening and prenatal diagnostic testing for genetic disorders among women of Asian descent in western countries. The Medline, CINAHL, ASSIA and PsycInfo databases were searched for the period of 1995 and 2010. Twenty-one studies met the inclusion criteria and were therefore reviewed. In general, Asian women were found to hold favourable attitudes towards testing. However, they reported a poorer understanding of testing than white women and not being offered a test, and were less able to make informed choices. Asian women in the UK and Australia were found to be less likely than their white counterparts to have undergone prenatal diagnosis, while such differences were not found in the USA and Canada. The equity of access to quality antenatal care, alongside comprehensive well thought out antenatal screening programmes, can be assured if strategies are in place which actively involve all ethnic groups and take account of social and cultural appropriateness for the population served. An understanding of broad factors that inform women's decision-making on test uptake would help health professionals provide women and their families with more culturally sensitive information and support that they may additionally need to make more informed choices. PMID- 22067009 TI - Effects of cysteine on the pharmacokinetics of docetaxel in rats with protein calorie malnutrition. AB - The objective of this study is to report the effects of cysteine on the pharmacokinetics of intravenous and oral docetaxel in rats with protein-calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of docetaxel were assessed using control, CC (control with cysteine), PCM and PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of docetaxel were further investigated through in vitro transport studies using rat intestine and Caco-2 cell monolayers. The AUCs (the areas under the plasma concentration-time curve from time zero to time infinity) of intravenous docetaxel in PCM rats were significantly greater than in the control rats because of the significant decrease in the hepatic CYP3A. In PCMC rats, the elevated AUCs in PCM rats returned to control levels. The AUC(0-6 h)s of oral docetaxel in PCM rats were significantly smaller than that in the control rats, mainly due to the decrease in gastrointestinal absorption. In CC and PCMC rats, oral cysteine supplement enhanced the gastrointestinal absorption of docetaxel probably via intestinal P-gp inhibition. If the present rat data could be expressed to humans, the alterations in docetaxel absorption and metabolism should be considered in designing a dosage regimen for cancer patients with PCM state after cysteine supplement. PMID- 22067010 TI - Exercise is an effective treatment modality for reducing cancer-related fatigue and improving physical capacity in cancer patients and survivors: a meta analysis. AB - The use of exercise interventions to manage cancer-related fatigue (CRF) is a rapidly developing field of study. However, results are inconsistent and difficult to interpret across the literature, making it difficult to draw accurate conclusions regarding the true effectiveness of exercise interventions for CRF management. The aims of this study were to apply a meta-analysis to quantitatively assess the effects of exercise intervention strategies on CRF, and to elucidate appropriate exercise prescription guidelines. A systematic search of electronic databases and relevant journals and articles was conducted. Studies were eligible if subjects were over the age of 18 years, if they had been given a diagnosis of or had been treated for cancer, if exercise was used to treat CRF as a primary or secondary endpoint, and if the effects of the intervention were evaluated quantitatively and presented adequate statistical data for analysis. A total of 16 studies, representing 1426 participants (exercise, 759; control, 667) were included in a meta-analysis using a fixed-effects model. The standardized mean difference effect size (SMD) was used to test the effect of exercise on CRF between experimental and control groups. The results indicate a small but significant effect size in favour of the use of exercise interventions for reducing CRF (SMD 0.26, p < 0.001). Furthermore, aerobic exercise programs caused a significant reduction in CRF (SMD 0.21, p < 0.001) and overall, exercise was able to significantly improve aerobic and musculoskeletal fitness compared with control groups (p < 0.01). Further investigation is still required to determine the effects of exercise on potential underlying mechanisms related to the pathophysiology of CRF. PMID- 22067011 TI - Pressure immobilization after North American Crotalinae snake envenomation. PMID- 22067012 TI - Pressure bandaging for North American snake bite? No! AB - This issue of Clinical Toxicology includes a Position Statement regarding the use of pressure immobilization for the pre-hospital treatment of North American Crotalinae envenomation. This Commentary discusses the background behind the creation of the Position Statement and explores the issues involved in applying science to real world public health recommendations and practice. PMID- 22067013 TI - Control of metal-enhanced fluorescence with pH- and thermoresponsive hybrid microgels. AB - In this paper, we report on the Ag nanoparticle-containing hybrid poly(N isopropylacrylamide-co-acrylic acid) (PNIPAM-co-PAA) microgels with pH- and thermoresponsive metal-enhanced fluorescence (MEF). The hybrid microgels were prepared by in situ reducing Ag salts to Ag nanoparticles in the PNIPAM-co-PAA microgels. According to the interaction distance-dependent nature of MEF effects, we can realize a controllable MEF effect by adjusting the average interaction distance between fluorophores and Ag nanoparticles due to the good stimuli responsive swelling-shrinking behavior of the hybrid microgels. The results show that MEF effect can be well tuned in the pH region 2-12 as well as the temperature region of 20-50 degrees C. By this method, an enhanced fluorescence detection can possibly be manipulated by adjusting external stimuli such as pH and temperature. PMID- 22067014 TI - An evaluation of a novel instrument for measuring macular pigment optical density: the MPS 9000. AB - PURPOSE: Of the antioxidants found in the human retina, only the macular carotenoid quantities can be estimated noninvasively (albeit in a collective fashion), thus facilitating study of their role in that tissue. The aim of this study was to evaluate concordance between macular pigment optical density (MPOD) values recorded on a commercially available instrument, the MPS 9000, with those of an already validated heterochromatic flicker photometry instrument. Also, we assessed and compared test-retest variability for each instrument. METHODS: Macular pigment optical density at 0.5 retinal eccentricity was measured using two different heterochromatic flicker photometers, the MPS 9000 and the Macular Densitometer(TM), in 39 healthy subjects. Test-retest variability was evaluated separately for each instrument by taking three readings over a 1-week period in 25 subjects. RESULTS: There was a moderate positive correlation for MPOD at 0.5 degrees of retinal eccentricity between the MPS 9000 and the Macular Densitometer described by the linear equation y = 0.763x + 0.172 (r = 0.68, p < 0.001, r(2) = 0.46); however, a paired-samples t-test showed a significant difference in terms of mean values, with a bias of lower MPOD values being yielded by the MPS 9000 (t = -4.103, p < 0.001). Bland-Altman analysis indicated only moderate agreement between the two instruments, reflected in 95% limits of agreement of 0.1 +/- 0.27. Inter-sessional repeatability, expressed as a coefficient of repeatability, ranged from 0.18 to 0.21 [mean (+/-SD): 0.19 (0.02)] for the MPS 9000 and from 0.11 to 0.12 [mean (+/-SD): 0.12 (0.01)] for the Macular Densitometer. CONCLUSION: The results demonstrate that the MPS 9000 consistently yields MPOD readings, which are lower than that found with the Macular Densitometer, and exhibits substantial test-retest variability. PMID- 22067015 TI - NAOMI: on the almost trivial task of reading molecules from different file formats. AB - In most cheminformatics workflows, chemical information is stored in files which provide the necessary data for subsequent calculations. The correct interpretation of the file formats is an important prerequisite to obtain meaningful results. Consistent reading of molecules from files, however, is not an easy task. Each file format implicitly represents an underlying chemical model, which has to be taken into consideration when the input data is processed. Additionally, many data sources contain invalid molecules. These have to be identified and either corrected or discarded. We present the chemical file format converter NAOMI, which provides efficient procedures for reliable handling of molecules from the common chemical file formats SDF, MOL2, and SMILES. These procedures are based on a consistent chemical model which has been designed for the appropriate representation of molecules relevant in the context of drug discovery. NAOMI's functionality is tested by round robin file IO exercises with public data sets, which we believe should become a standard test for every cheminformatics tool. PMID- 22067016 TI - Terminal hematuria associated with oral isotretinoin treatment in a patient with acne vulgaris. AB - Hematuria is defined as the abnormal presence of red blood cells in the urine and is commonly divided into gross and microscopic hematuria. Terminal hematuria occurs at the end of the urine stream and may have a prostatic, bladder, or trigonal cause. Here, we present a 16-year-old boy who developed terminal hematuria after 1 month of treatment with isotretinoin for acne vulgaris. This side effect of isotretinoin is not reported in the literature. This is the first case report. PMID- 22067017 TI - Electrical properties and magnetic response of cobalt germanosilicide nanowires. AB - The effects of partial substitution of Ge for Si in cobalt germanosilicide (CoSi(1-x)Ge(x) and Co(2)Si(1-x)Ge(x)) nanowires (NWs) on the electrical transport, magnetic properties, and magnetoresistance (MR) have been investigated. Cobalt germanosilicide NWs were synthesized by a spontaneous chemical vapor transport growth method. The Ge concentration can be selectively controlled from 0 to 15% and 0-50% for CoSi(1-x)Ge(x) and Co(2)Si(1-x)Ge(x) NWs, respectively, by varying the reaction temperature. Electrical measurements showed that the resistivities of CoSi(1-x)Ge(x) NWs are 90, 60, 30, and 23 MUOmega-cm for x = 0, 0.01, 0.05, and 0.15, respectively. Therefore, the electrical resistivity of CoSi(1-x)Ge(x) NWs was found to decrease significantly with an increasing Ge concentration, which is believed to be a result of the band gap narrowing. On the other hand, the Co(2)Si(1-x)Ge(x) (x <= 0.5) NWs exhibited ferromagnetism at 300 K, which is attributed to the uncoordinated Co atoms on the NW surface and spin-glass behavior at low temperature. The highest MR response of Co(2)Si(1-x)Ge(x) NWs occurred at x = 0.5, where a MR ratio of 11.7% can be obtained at 10-25 K with a magnetic field of 8 T. The enhanced physical properties of cobalt germanosilicide NWs with Ge substitution shall lead to promising application in the fabrication of nanodevices, including spintronics and serving as the gate and interconnect material. PMID- 22067020 TI - Women's reported weight: is there a discrepancy? AB - OBJECTIVE: To compare self-reported pre-pregnancy weight & delivery weight with documented pre-pregnancy & delivery weight and determine whether there are differences compared with the Institute of Medicine's (IOM) guidelines. METHODS: This is a retrospective analysis of 234 women. Inclusion criteria included documented height, self-reported pre-pregnancy weight, self-reported delivery weight, documented pre-pregnancy weight +/- 12 weeks from last menstrual period, and documented delivery weight +/- 2 weeks from delivery. We determined the difference between self-reported pre-pregnancy weight vs. documented pre pregnancy weight and self-reported delivery weight vs. documented delivery weight. Using documented pre-pregnancy weight and documented delivery weight, we calculated gestational weight gain (GWG) relative to IOM criteria. RESULTS: Self reported pre-pregnancy weight was 2.94 kg less than documented pre-pregnancy weight (p < 0.0001). Self-reported BMI was 1.11 mg/kg(2) less than documented BMI (p < 0.0001). Self-reported GWG was 3.01 kg greater than documented GWG (p < 0.0001). Ninety-eight percent of normal weight correctly classified pregravid BMI in contrast to 86% of obese (p < 0.005) and 73% of overweight (p < 0.001). CONCLUSIONS: Overweight and obese women underestimated self-reported pre pregnancy weight & overestimated GWG, thereby mistakenly categorizing IOM guidelines. PMID- 22067021 TI - Expression of ghrelin is correlated to a favorable outcome in invasive breast cancer. AB - BACKGROUND: Expression of the peptide hormones ghrelin and obestatin has previously been demonstrated in human mammary glands. However, the clinical implications of the expression of these peptides in breast cancer are unclear. The aim of this study was to investigate the potential clinical value of ghrelin and obestatin as breast cancer biomarkers. METHODS: A tissue microarray containing breast cancer specimens from 144 patients was immunostained with antibodies directed towards ghrelin and obestatin. Using varying cut-offs, the expression of the two peptides was evaluated and correlated to previously known prognostic factors in breast cancer and to the outcome. Cox regression analysis was used to assess whether these markers may predict survival of breast cancer patients. RESULTS: Moderate to strong immunoreactivity for ghrelin and obestatin was observed in 71.5% and 77.1% of the cases, respectively. Ghrelin and obestatin expression was significantly but weakly correlated to low histological grade, estrogen receptor positivity, small tumor size and low proliferation. Only ghrelin expression was significantly correlated to better recurrence-free and breast cancer-specific survival (HR = 0.3-0.4, p = 0.02-0.05) in both uni- and multivariate analyses. The optimal cut-off was any ghrelin expression versus none. Reproducibility between the two readers was very good for both stainings with kappa values of 0.94-1.00. CONCLUSIONS: Patients with tumors expressing ghrelin had 2.5-3 times lower risk for recurrence or breast cancer death than those lacking ghrelin expression. Ghrelin expression is easily assessable with high reproducibility using immunohistochemistry. Further investigations are needed to establish the clinical significance of ghrelin as a biomarker in breast cancer. PMID- 22067022 TI - Multi-objective behavioural mechanisms are adopted by foraging animals to achieve several optimality goals simultaneously. AB - 1. Animals foraging for resources are under a variety of selective pressures, and separate optimality models have been developed predicting the optimal reproductive strategies they should adopt. 2. In most cases, the proximate behavioural mechanisms adopted to achieve such optimality goals have been identified. This is the case, for example, for optimal patch time and sex allocation in insect parasitoids. However, behaviours modelled within this framework have mainly been studied separately, even though real animals have to optimize some behaviours simultaneously. 3. For this reason, it would be better if proximate behavioural rules were designed to attain several goals simultaneously. Despite their importance, such multi-objective proximate rules remain to be discovered. 4. Based on experiments on insect parasitoids that simultaneously examine their optimal patch time and sex allocation strategies, it is shown here that animals can adopt multi-objective behavioural mechanisms that appear consistent with the two optimal goals simultaneously. 5. Results of computer simulations demonstrate that these behavioural mechanisms are indeed consistent with optimal reproductive strategies and have thus been most likely selected over the course of the evolutionary time. PMID- 22067023 TI - Competition between two wood-degrading fungi with distinct influences on residues. AB - Many wood-degrading fungi colonize specific types of forest trees, but often lack wood specificity in pure culture. This suggests that wood type affects competition among fungi and indirectly influences the soil residues generated. While assessing wood residues is an established science, linking this information to dominant fungal colonizers has proven to be difficult. In the studies presented here, we used isolate-specific quantitative PCR to quantify competitive success between two distinct fungi, Gloeophyllum trabeum and Irpex lacteus, brown and white rot fungi, respectively, colonizing three wood types (birch, pine, oak). Ergosterol (fungal biomass), fungal species-specific DNA copy numbers, mass loss, pH, carbon fractions, and alkali solubility were determined 3 and 8 weeks postinoculation from replicate wood sections. Quantitative PCR analyses indicated that I. lacteus consistently outcompeted G. trabeum, by several orders of magnitude, on all wood types. Consequently, wood residues exhibited distinct characteristics of white rot. Our results show that competitive interactions between fungal species can influence colonization success, and that this can have significant consequences on the outcomes of wood decomposition. PMID- 22067024 TI - CD154 as a potential early molecular biomarker for rapid quantification analysis of active Staphylococcus enterotoxin A. AB - Staphylococcus aureus is a major bacterial pathogen producing a group of 21 enterotoxins (SEs). These enterotoxins have two separate but related biological activities. They cause gastroenteritis, and they function as superantigens that activate large numbers of T cells. In the current study, we demonstrate that short-term ex vivo exposure of primary naive CD4(+) T-cells to SEA induces differential expression of the T cell surface receptor CD154 in a time- and dose dependent manner. In addition, we show that SEA induces higher CD154 protein expression and higher splenocyte cell proliferation compared with SEB. We also demonstrate that expression of CD154 can be used for rapid detection of active SEA in milk. PMID- 22067034 TI - Yeast communities associated with the bulk-soil, rhizosphere and ectomycorrhizosphere of a Nothofagus pumilio forest in northwestern Patagonia, Argentina. AB - Soil microorganisms play an important role in soil quality and they interact closely with vegetation. Little is known about yeast diversity and function in forest soil ecosystems and their interactions with other biotic soil components, particularly in the mycorrhizosphere. We studied the diversity of yeasts inhabiting the bulk-soil, rhizosphere and ectomycorrhizosphere of a Nothofagus pumilio forest in Nahuel Huapi National Park (Bariloche, Argentina). Ectomycorrhizal infection was observed in all N. pumilio trees studied. A total of 126 yeast isolates were obtained, including 18 known and three possibly new species. Basidiomycetous yeasts were predominant in all soil fractions, and the most frequently isolated species was Cryptococcus podzolicus. Diversity indices and multivariate analyses were used to study and compare yeast communities in the bulk-soil, rhizosphere and ectomycorrhizosphere. Yeasts able to ferment glucose were found associated with the rhizosphere. Many of the recovered yeast species were associated with lignocelluloses compound degradation, which suggest that yeast plays an important role as a decomposer in these forest soils. Each soil fraction has a distinct yeast assemblage related to their physiologic capacities and soil nutrient availability. PMID- 22067035 TI - MicroRNA signature in diabetic wound healing: promotive role of miR-21 in fibroblast migration. AB - A major complication of diabetes mellitus is the disruption of normal wound repair process, characterised by insufficient production of growth factors. A molecular genetic approach wherein resident cells synthesise and deliver the growth factors to the wound site would be a powerful therapeutic strategy to treat diabetic wounds. One such molecular approach could be the application of microRNAs (miRNAs). This study reports differential expression of miRNAs related to cell development and differentiation, during wound healing in diabetic mice. Comparison of skin tissue from normal and diabetic mice showed that 14 miRNAs were differentially expressed in diabetic skin; miR-146b and miR-21 were the most noteworthy. Expression pattern of these miRNAs was also altered during healing of diabetic wounds. A subset of miRNAs (miR-20b, miR-10a, miR-10b, miR-96, miR-128, miR-452 and miR-541) exhibited similar basal levels in normal and diabetic skins, but displayed dysregulation during healing of diabetic wounds. Amongst the miRNAs studied, miR-21 showed a distinct signature with increased expression in diabetic skin but decreased expression during diabetic wound healing. We analysed the role of miR-21 in fibroblast migration, because migration of fibroblasts into the wound area is an important landmark facilitating secretion of growth factors and migration of other cell types into the wound, thus enhancing the healing process. Using gain-of and loss-of function approaches, we show that miR-21 is involved in fibroblast migration. Our preliminary studies implicate an important role for miRNAs in the pathogenesis of diabetic wounds. PMID- 22067036 TI - Development and evaluation of new primers for PCR-based identification of type II fimA of Porphyromonas gingivalis. AB - For more accurate PCR-based identification of Porphyromonas gingivalis harboring genotype II fimA, the most prevalent type in periodontitis patients, a new primer set was developed and evaluated. The previous type II primers hybridized to the DNA of P gingivalis strains harboring type Ib as well as type II fimA, while the new primers specifically amplified only the DNA fragment of type II fimA. In the investigation using mixed bacterial culture and 155 clinical samples from peri implantitis patients, the new primers increased the accuracy of PCR-based detection of type II fimA by excluding false-negatives as well as false positives. PMID- 22067037 TI - Extrinsic mechanism obstructing the opening of a prosthetic mitral valve: an unusual case of suture entrapment. AB - Obstruction to a prosthetic cardiac valve is a well-recognized complication of cardiac valve replacement. Malfunction of the mobile component of a prosthetic valve to open or close correctly may occur in consequence of intrinsic or extrinsic causes (thrombus, vegetation, entrapment of left ventricular myocardium, suture entanglement, and pannus formation) that may result prosthetic valve stenosis and/or insufficiency. In the case we report a 48-year-old female with valve dysfunction occurred early after surgery, as one valve leaflet was only able to partially open due to suture entrapment. PMID- 22067038 TI - Development and molecular characterization of wheat--Aegilops kotschyi addition and substitution lines with high grain protein, iron, and zinc. AB - Over two billion people, depending largely on staple foods, suffer from deficiencies in protein and some micronutrients such as iron and zinc. Among various approaches to overcome protein and micronutrient deficiencies, biofortification through a combination of conventional and molecular breeding methods is the most feasible, cheapest, and sustainable approach. An interspecific cross was made between the wheat cultivar 'Chinese Spring' and Aegilops kotschyi Boiss. accession 396, which has a threefold higher grain iron and zinc concentrations and about 33% higher protein concentration than wheat cultivars. Recurrent backcrossing and selection for the micronutrient content was performed at each generation. Thirteen derivatives with high grain iron and zinc concentrations and contents, ash and ash micronutrients, and protein were analyzed for alien introgression. Morphological markers, high molecular weight glutenin subunit profiles, anchored wheat microsatellite markers, and GISH showed that addition and substitution of homoeologous groups 1, 2, and 7 chromosomes of Ae. kotschyi possess gene(s) for high grain micronutrients. The addition of 1U/1S had high molecular weight glutenin subunits with higher molecular weight than those of wheat, and the addition of 2S in most of the derivatives also enhanced grain protein content by over 20%. Low grain protein content in a derivative with a 2S-wheat translocation, waxy leaves, and absence of the gdm148 marker strongly suggests that the gene for higher grain protein content on chromosome 2S is orthologous to the grain protein QTL on the short arm of group 2 chromosomes. PMID- 22067039 TI - Concerted proton-electron transfers. Consistency between electrochemical kinetics and their homogeneous counterparts. AB - The concerted proton-electron transfer (CPET) oxidation of phenol with water (in water) and hydrogen phosphate as proton acceptors provides a good example for testing the consistency of the electrochemical and homogeneous approaches to a reaction, the comprehension of which raises more mechanistic and kinetic challenges than that of a simple outer-sphere electron transfer. Comparison of the intrinsic kinetic characteristics (obtained at zero driving force of the CPET reaction) shows that consistency is indeed observed after a careful identification and quantitation of side factors (electrical work terms, image force effects). Water (in water) appears as a better intrinsic proton acceptor than hydrogen phosphate in both cases in terms of reorganization energy and pre exponential factor, corroborating the mechanism by which electron transfer is concerted with Grotthus-type proton translocation in water. Detailed compared analysis of the approaches also revealed that modest but significant electric field effects may be at work in the electrochemical case. Comparison with phenoxide ion oxidation, taken as a reference outer-sphere electron transfer, points to a CPET precursor complex that possesses a precise spatial structure allowing the formation of one or several H-bonds as required by the occurrence of the CPET reaction, thus decreasing considerably the number of efficient collisions compared with those undergone by structureless spherical reactants. PMID- 22067040 TI - Enantioselective boronate additions to N-acyl quinoliniums catalyzed by tartaric acid. AB - Tartaric acid catalyzes the asymmetric addition of vinylboronates to N-acyl quinoliniums, affording highly enantioenriched dihydroquinolines. The catalyst serves to activate the boronate through a ligand-exchange reaction and generates the N-acyl quinolinium in situ from the stable quinoline-derived N,O-acetal. PMID- 22067041 TI - Factors associated with lobar vs. non-lobar intracerebral hemorrhage. AB - OBJECTIVES: The relationship between body mass index (BMI) and stroke subtypes has received more research attention than that between BMI and location of intracerebral hemorrhage (ICH). Lobar hemorrhage (LH) differs from non-LH primarily in terms of etiology, i.e. cerebral amyloid angiopathy is the main cause of LH. This study aimed to determine the relationship between BMI and ICH. MATERIALS AND METHODS: In this retrospective study involving 460 consecutive patients with ICH, BMI was significantly lower in LH than for other ICH locations. BMI categories were underweight (BMI < 18.5 kg/m(2)), normal weight (18.5-23.0 kg/m(2)), overweight (23.0-27.5 kg/m(2)), or obesity (>=27.5 kg/m(2)). Outcome at 1 year was evaluated by the modified Rankin Scale (mRS). We investigated the relationship of BMI and other clinical characteristics with LH and non-LH. RESULTS: LH was associated with age (>70 years), underweight, unfavorable outcome (mRS >=3), and daily alcohol consumption. Hypertension and intraventricular bleeding were significantly less common in patients with LH than those with non-LH. CONCLUSIONS: Alongside risk factors conventionally thought to be related to LH, underweight may also be a LH-related factor, specifically in the elderly. PMID- 22067042 TI - Tissue engineering of lips and muco-cutaneous junctions: in vitro development of tissue engineered constructs of oral mucosa and skin for lip reconstruction. AB - We report for the first time the fabrication of a three-dimensional tissue structure containing, in a continuous layer, the morphological features of a lip: epidermal skin, vermillion, and oral mucosa. This tissue engineered muco cutaneous (M/C) equivalent was manufactured using human oral and skin keratinocytes grown on an acellular, nonimmunogenic dermal equivalent (AlloDerm((r))) to produce a tissue equivalent with similar anatomic and handling properties as native human lips. Confirmation of the structural composition of the construct was performed using routine histology and immunohistochemistry by identification of epithelial markers that are differentially expressed in separate anatomic areas of the lips. These full-thickness human lip skin equivalents can be used in surgical lip reconstruction in individuals suffering from lip loss from cancer, congenital deformations, and injuries after accidents. We propose this technique can be used as a general basis for tissue engineering of M/C junctions in other parts of the body, such as anus and vagina. PMID- 22067043 TI - The roles of peroxidase and phospholipase A2 activities of peroxiredoxin 6 in protecting pulmonary microvascular endothelial cells against peroxidative stress. AB - AIMS: Peroxiredoxin 6 (Prdx6), a bifunctional enzyme with glutathione peroxidase and phospholipase A(2) (PLA(2)) activities, has been demonstrated as playing a critical role in antioxidant defense of the lung. Our aim was to evaluate the relative role of each activity in Prdx6-mediated protection of mouse pulmonary microvascular endothelial cells (PMVECs) against the peroxidative stress of treatment with tert-butyl hydroperoxide (tBOOH). RESULTS: PMVEC from Prdx6 null mice showed increased lethality on tBOOH exposure (50-200 MUM) compared with wild type (WT) controls. Treatment with 1-hexadecyl-3-trifluoroethylglycero-sn-2 phosphomethanol (MJ33), a Prdx6 PLA(2) activity inhibitor, increased the sensitivity of WT cells to peroxidative stress, but did not further sensitize Prdx6 null cells. Lethality in Prdx6 null PMVEC was "rescued" by transfection with a construct leading to the expression of WT rat Prdx6. Expression of mutant Prdx6 with either peroxidase activity or PLA(2) activity alone each partially rescued the survival of Prdx6 null cells, while constructs with both active sites mutated failed to rescue. Co-transfection with two different constructs, each expressing one activity, rescued cells as well as the WT construct. INNOVATION AND CONCLUSION: Contrary to the general assumption that the peroxidase activity is the main mechanism for Prdx6 antioxidant function, these results indicate that the PLA(2) activity also plays a substantial role in protecting cells against oxidant stress caused by an exogenous hydroperoxide. PMID- 22067044 TI - Effect of vehicle systems, pH and enhancers on the permeation of highly lipophilic aripiprazole from Carbopol 971P gel systems across human cadaver skin. AB - The objective of this study was to investigate the effect of vehicle systems, pH and enhancers on the permeation of a highly lipophilic basic drug aripiprazole (ARPZ) through human cadaver skin. Solubility of ARPZ in single, binary, tertiary, and quaternary vehicle systems of N-methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), water, ethanol and isopropyl myristate (IPM) was studied. Gel formulations of 5% ARPZ were developed with 0.5% Carbopol 971P in quaternary vehicle systems consisting of NMP, DMSO, water and ethanol or IPM at optimum ratio of 40/40/5/15. The effect of pH of the gel formulations and fatty acids with different chain lengths on the permeation was studied. The flux of ARPZ from gel formulation with IPM and ethanol was comparable. A four fold increase in APRZ flux was observed when the pH of the gel systems was lowered from pH 8.2 to pH 6 or pH 7. For fatty acids, the order of flux is lauric acid > myristic acid > caprylic acid > oleic acid. In all the cases, in vitro permeation rate of ARPZ through human cadaver skin followed zero order kinetics. This study demonstrated that ARPZ in tertiary vehicle system of NMP/DMSO/water/IPM at ratio of 40/40/5/15 and gel system of Carbopol 971P with pH 7 is a promising candidate for transdermal delivery. PMID- 22067045 TI - Naturally occurring structural isomers in serum IgA1 o-glycosylation. AB - IgA is the most abundantly produced antibody and plays an important role in the mucosal immune system. Human IgA is represented by two isotypes, IgA1 and IgA2. The major structural difference between these two subclasses is the presence of nine potential sites of O-glycosylation in the hinge region between the first and second constant region domains of the heavy chain. Thr(225), Thr(228), Ser(230), Ser(232) and Thr(236) have been identified as the predominant sites of O-glycan attachment. The range and distribution of O-glycan chains at each site within the context of adjacent sites in this clustered region create a complex heterogeneity of surface epitopes that is incompletely defined. We previously described the analysis of IgA1 O-glycan heterogeneity by use of high resolution LC-MS and electron capture dissociation tandem MS to unambiguously localize all amino acid attachment sites in IgA1 (Ale) myeloma protein. Here, we report the identification and elucidation of IgA1 O-glycopeptide structural isomers that occur based on amino acid position of the attached glycans (positional isomers) and the structure of the O-glycan chains at individual sites (glycan isomers). These isomers are present in a model IgA1 (Mce1) myeloma protein and occur naturally in normal human serum IgA1. Variable O-glycan chains attached to Ser(230), Thr(233) or Thr(236) produce the predominant positional isomers, including O-glycans composed of a single GalNAc residue. These findings represent the first definitive identification of structural isomeric IgA1 O-glycoforms, define the single-site heterogeneity for all O-glycan sites in a single sample, and have implications for defining epitopes based on clustered O-glycan variability. PMID- 22067046 TI - Fibroblasts contribute to melanoma tumor growth and drug resistance. AB - The role of tumor-stromal interactions in progression is generally well accepted, but their role in initiation or treatment is less well understood. It is now generally agreed that, rather than consisting solely of malignant cells, tumors consist of a complex dynamic mixture of cancer cells, host fibroblasts, endothelial cells and immune cells that interact with each other and microenvironmental factors to drive tumor progression. We are particularly interested in stromal cells (for example fibroblasts) and stromal factors (for example fibronectin) as important players in tumor progression since they have also been implicated in drug resistance. Here we develop an integrated approach to understand the role of such stromal cells and factors in the growth and maintenance of tumors as well as their potential impact on treatment resistance, specifically in application to melanoma. Using a suite of experimental assays we show that melanoma cells can stimulate the recruitment of fibroblasts and activate them, resulting in melanoma cell growth by providing both structural (extracellular matrix proteins) and chemical support (growth factors). Motivated by these experimental results we construct a compartment model and use it to investigate the roles of both stromal activation and tumor aggressiveness in melanoma growth and progression. We utilize this model to investigate the role fibroblasts might play in melanoma treatment resistance and the clinically observed flare phenomenon that is seen when a patient, who appears resistant to a targeted drug, is removed from that treatment. Our model makes the unexpected prediction that targeted therapies may actually hasten tumor progression once resistance has occurred. If confirmed experimentally, this provocative prediction may bring important new insights into how drug resistance could be managed clinically. PMID- 22067047 TI - Analysis of the bone metabolism by quantitative computer tomography and clinical chemistry in a primate model (Callithrix jacchus). AB - BACKGROUND: Common marmosets are widely used as experimental primates; however, little is still known about their bone physiology. Therefore, the aim of our study was to analyse body weight, age and bone-specific blood parameters in relation to morphological bone parameters. METHODS: Fifty-eight common marmosets were analysed for blood calcium (Ca), inorganic phosphor (P(i) ), alkaline phosphatase (AP) and 17-beta-estradiol (E2). The examination of bone parameters was undertaken in the lumbar spine by computer tomography. RESULTS: There was a correlation between bone mineral density (BMD) and body weight, trabecular area ratio and polar moment as well as between BMD and AP or Ca (only males), whereas there were no correlations between BMD and age, P(i) or E2 in all analysed genders. CONCLUSIONS: Our data support the assumption that the common marmoset is a reliable primate model to study changes in bone metabolism because of the similarity of our results to humans. PMID- 22067048 TI - Complement system activation and endothelial dysfunction in patients with age related macular degeneration (AMD): possible relationship between AMD and atherosclerosis. AB - Age-related macular degeneration (AMD) shares several pathological and epidemiological similarities with systemic atherosclerosis (AS). First, an association between AS and AMD is apparent from the analyses of the histological and biochemical structure of atherosclerotic plaques in the vascular walls and retinal drusen, the hallmark of AMD. Second, there is considerable evidence implicating endothelial dysfunction in the pathogenesis of both disorders, and cellular oxidative stress appears to be a common denominator underlying this process. Moreover, there are observations that the complement system (CS) triggering inflammatory response contributes to the onset and advancement of both diseases. The CS plays a role in the generation of drusen and neovascularization in AMD as well as in vascular endothelium activation, cell damage and ultimately atherosclerotic plaque formation in the course of systemic arteriosclerosis. It is widely recognized that both AMD and AS are not only related to local stimulation of the CS, but also result in its systemic activation. In addition, a specific Y402H polymorphism of the complement inhibitor factor H has been found to be associated with the incidence of both AMD and AS. Here, we propose a linking hypothesis between CS activation, endothelial dysfunction and the pathogenesis of two common and age-related pathological processes, AS and AMD. We also discuss the potential therapeutic value of pharmacological modulation of CS activation in these disorders. PMID- 22067049 TI - Atypical molluscum contagiosum accompanied by CD30-positive lymphoid infiltrates. AB - Atypical presentations of molluscum contagiosum require histophathologic examination and may show pleomorphic lymphocytic infiltrates of a reactive nature, mimicking cutaneous lymphoproliferative diseases. Serial sections of specimens or polymerase chain reactions to show T-cell receptor clonality may be helpful for differential diagnosis. We report a case of atypical molluscum contagiosum accompanied by atypical lymphocytic infiltration showing CD30 positivity. PMID- 22067050 TI - Nanopore analysis of individual RNA/antibiotic complexes. AB - Nanopores in thin solid-state membranes are used to rapidly analyze individual RNA/drug complexes. The interactions of a truncated A-site RNA model of the prokaryotic ribosome with aminoglycoside antibiotics are characterized by passing individual molecules through a 3-3.5 nm diameter pore fabricated in a 8-10 nm thick silicon nitride membrane. Complexes of the A-site RNA with aminoglycosides can be distinguished from unbound A-site based on the ion current signatures produced as they pass through the nanopores. Counting the fraction of free and drug-bound molecules affords label-free drug-RNA binding isotherms consistent with literature reports and with data generated using independent fluorescence based assays. Our measurements are supported by molecular dynamics simulations, which illustrate the relationship between the ionic current and complexation of the A-site RNA with paramomycin, a prototypical aminoglycoside antibiotic. PMID- 22067051 TI - Ectopic expression of FaDREB2 enhances osmotic tolerance in paper mulberry. AB - Dehydration-responsive element binding (DREB) proteins are a subfamily of AP2/ERF transcription factors that have been shown to improve tolerance to osmotic stresses in plants. To improve the osmotic stress tolerance of paper mulberry (Broussonetia papyrifera L. Vent), an economically important tree, we transformed it with a plasmid carrying tall fescue (Festuca arundinacea Schreb) FaDREB2 under the control of CaMV 35S. The ectopic expression of FaDREB2 did not cause growth retardation, and the paper mulberry seedlings expressing FaDREB2 showed higher salt and drought tolerance than wild-type plants (WT). After 13 d of withholding water, or 15 d in the presence of 250 mM NaCl, all the WT plants died, while the plants expressing FaDREB2 survived. The FaDREB2 transgenic plants had higher leaf water and chlorophyll contents, accumulated more proline and soluble sugars, and had less membrane damage than the WT plants under high salt and water-deficient conditions. Taken together, the results indicate the feasibility of improving tolerance to multiple environmental stresses in paper mulberry seedlings via genetic engineering, by introducing FaDREB2, which promotes the increased accumulation of osmolytes (soluble sugars and proline), to counter osmotic stresses caused by abiotic factors. PMID- 22067052 TI - Two-stage bone expansion technique using spear-shaped implants associated with overlapped flap: a case report. AB - The conventional method of ridge expansion uses a mucoperiosteal flap elevation to allow bone corticotomy, which is followed by bone expansion performed with chisels and bone expanders. To facilitate corticotomy and avoid flap elevation, bone expansion can be performed in 2 stages. This case report presents a modified 2-stage bone expansion technique to achieve better implant stabilization and wound closure. This modified approach may be an efficient procedure for minimizing complications. PMID- 22067053 TI - Annual research review: impact of advances in genetics in understanding developmental psychopathology. AB - It was hoped that diagnostic guidelines for, and treatment of, child psychiatric disorders in DSM-5 would be informed by the wealth of clinical genetic research related to neurodevelopmental disorders. In spite of remarkable advances in genetic technology, this has not been the case. Candidate gene, genome-wide association, and rare copy number variant (CNV) studies have been carried out for attention-deficit/hyperactivity disorder (ADHD), Autism, Tourette's Syndrome, and schizophrenia, with intriguing results, but environmental factors, incomplete penetrance, pleiotropy, and genetic heterogeneity, underlying any given phenotype have limited clinical translation. One promising approach may be the use of developmental brain imaging measures as more relevant phenotypes. This is particularly important, as subtle abnormalities in timing and expression of gene pathways underlying brain development may well link these disorders and be the ultimate target of treatments. PMID- 22067054 TI - Tracking the autochthonous carbon transfer in stream biofilm food webs. AB - Food webs in the rhithral zone rely mainly on allochthonous carbon from the riparian vegetation. However, autochthonous carbon might be more important in open canopy streams. In streams, most of the microbial activity occurs in biofilms, associated with the streambed. We followed the autochthonous carbon transfer toward bacteria and grazing protozoa within a stream biofilm food web. Biofilms that developed in a second-order stream (Thuringia, Germany) were incubated in flow channels under climate-controlled conditions. Six-week-old biofilms received either 13C- or 12C-labeled CO2, and uptake into phospholipid fatty acids was followed. The dissolved inorganic carbon of the flow channel water became immediately labeled. In biofilms grown under 8-h light/16-h dark conditions, more than 50% of the labeled carbon was incorporated in biofilm algae, mainly filamentous cyanobacteria, pennate diatoms, and nonfilamentous green algae. A mean of 29% of the labeled carbon reached protozoan grazer. The testate amoeba Pseudodifflugia horrida was highly abundant in biofilms and seemed to be the most important grazer on biofilm bacteria and algae. Hence, stream biofilms dominated by cyanobacteria and algae seem to play an important role in the uptake of CO2 and transfer of autochthonous carbon through the microbial food web. PMID- 22067055 TI - Worldwide detection and identification of new and old rickettsiae and rickettsial diseases. AB - To determine the prevalence and distribution of rickettsial pathogens around the world, scientists have relied more and more upon molecular techniques in addition to serological and culture methods. The ease of use and sensitivity/specificity of molecular techniques such as quantitative real-time PCR assays and multilocus sequence typing have lead to an increase in reports of the detection and identification of new and old rickettsiae in previously known and in new endemic regions. These assays have been successfully used with clinical samples such as serum, blood, and tissue biopsies and with environmental samples such as arthropod vectors including ticks, fleas, lice, and mites, and blood and tissue specimens from small mammal collections and from wild and domestic large animals. These methods have lead to the detection of new and old rickettsial pathogens often in new locations leading investigators to suggest new regions of risk of these rickettsioses. PMID- 22067056 TI - Effect of a multi-species synbiotic formulation on fecal bacterial microbiota of healthy cats and dogs as evaluated by pyrosequencing. AB - The effect of a multi-species synbiotic on the fecal microbiota of healthy cats (n = 12) and dogs (n = 12) was evaluated. The synbiotic (containing 5 * 10(9) CFU of a mixture of seven probiotic strains, and a blend of fructooligosaccharides and arabinogalactans) was administered daily for 21 days. Fecal and serum samples were collected before, during, and up to 3 weeks after administration. Changes in the fecal microbiota were analyzed using denaturing gradient gel electrophoresis, 16S rRNA gene libraries, quantitative real-time PCR, and 16S rRNA gene 454-pyrosequencing. Probiotic species were detectable in 10/12 dogs and 11/12 cats during product administration. Abundances of Enterococcus and Streptococcus spp. were significantly increased in at least one time point during administration, and returned to baseline abundance after treatment was discontinued. No changes in the major bacterial phyla were identified on 454-pyrosequencing. No adverse gastrointestinal effects were recorded and no significant changes in gastrointestinal function or immune markers were observed during the study period. This study shows that while the ingestion of probiotics and prebiotics does not appear to alter the predominant bacterial phyla present in feces, supplementation with the investigated synbiotic leads to an increased abundance of probiotic bacteria in the feces of healthy cats and dogs. PMID- 22067057 TI - Developing a new clinical tool for diagnosing chronic Q fever: the Coxiella ELISPOT. AB - Definitively establishing a clinical diagnosis of chronic Q fever remains challenging, as the diagnostic performance of both conventional serological tests and PCR is limited. Given the importance of an early diagnosis of chronic Q fever, there is a need for a reliable diagnostic test. We developed an enzyme linked immunospot assay to measure Coxiella burnetii (C. burnetii)-specific T cell responses (Coxiella ELISPOT) to both phase I and phase II antigens and tested convalescent Q fever patients (without chronic disease, n = 9) and patients with an established diagnosis of chronic Q fever (n = 3). The Coxiella ELISPOT adequately identified convalescent Q fever patients from healthy controls by demonstrating C. burnetii-specific T-cell interferon-gamma production to both phase I and phase II antigens. Compared to convalescent Q fever patients, chronic Q fever patients showed a distinct Coxiella ELISPOT profile characterized by a much higher spot count for both phase I and phase II (18-fold for phase II, 8 fold higher for phase I) and a consistent shift towards more phase I reactivity. The diagnostic potential of the Coxiella ELISPOT is promising and warrants further investigation. PMID- 22067058 TI - A randomized controlled pilot study of a brief web-based mindfulness training. AB - BACKGROUND: Mindfulness has been shown to be effective in treating various medical and mental problems. Especially its incorporation in cognitive behavioural interventions has improved long-term outcomes of those treatments. It has also been shown, that brief mindfulness-based trainings are effective in reducing distress. There have been few web-based interventions incorporating mindfulness techniques in their manual and it remains unclear whether a brief web based mindfulness intervention is feasible. METHODS: Out of 50 adults (different distress levels; exclusion criteria: <18 years, indication of psychotic or suicidal ideation in screening) who were recruited via e-mail and screened online, 49 were randomized into an immediate 2-weeks-treatment group (N=28) or a waitlist-control group (N=21), starting with a 2-week delay. Distress (BSI), perceived stress (PSQ), mindfulness (FMI), as well as mood and emotion regulation (PANAS/SEK-27) were measured at pre-, post- and 3-month follow-up (3MFU). Intention-to-treat analyses using MI for missing data and per-protocol analyses (>=50% attendance) were performed. RESULTS: 26 participants of the treatment group completed post-measures. Most measures under ITT-analysis revealed no significant improvement for the treatment group, but trends with medium effect sizes for PSQ (d=0.46) and PANASneg (d=0.50) and a small, non-significant effect for FMI (d=0.29). Per-protocol analyses for persons who participated over 50% of the time revealed significant treatment effects for PSQ (d=0.72) and PANASneg (d=0.77). Comparing higher distressed participants with lower distressed participants, highly distressed participants seemed to profit more of the training in terms of distress reduction (GSI, d=0.85). Real change (RCI) occurred for PSQ in the treatment condition (OR=9). Results also suggest that participants continued to benefit from the training at 3MFU. CONCLUSION: This study of a brief web-based mindfulness training indicates that mindfulness can be taught online and may improve distress, perceived stress and negative affect for regular users. Although there were no significant improvements, but trends, for most measures under ITT, feasibility of such a program was demonstrated and also that persons continued to use techniques of the training in daily life. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00003209. PMID- 22067059 TI - A case of recurrent earthquake stress cardiomyopathy with a differing wall motion abnormality. AB - We present the case of a Caucasian woman who survived two major earthquakes, presenting on each occasion with stress cardiomyopathy, but with a different pattern of regional wall motion abnormality on the second occasion. The first Christchurch earthquake struck on September 4, 2010. At 7.1 on the Richter scale, it was larger than the major Haiti quake, but miraculously there were no direct fatalities. In the week following, eight women meeting modified Mayo criteria for stress cardiomyopathy presented to Christchurch Hospital. The second Christchurch earthquake was on February 22, 2011. It measured 6.4 on the Richter scale and caused 180 direct fatalities. In the week following this earthquake, 24 women were admitted with stress cardiomyopathy. One patient presented after both earthquakes. This 76-year-old woman first presented on September 4 with 10 hours of chest pain. Electrocardiogram showed inferolateral deep T-wave inversion and QT prolongation. TnI peaked at 0.81 MUg/L. Coronary angiography demonstrated diffuse atheroma with a moderate mid LAD lesion that was stented at the time. Echocardiography showed a classic takotsubo pattern. Her follow-up echocardiogram on September 28 was normal and she was completely well at that point. However, during the second earthquake of February 22, she again developed chest pain and shortness of breath. TnI peaked at 1.3 MUg/L. Echocardiogram showed a midwall variant takotsubo with apical sparing. She was discharged from hospital on the 25th, planning to leave Christchurch for a new home in another city, but returned for follow-up echocardiogram on July 27. This was normal. PMID- 22067060 TI - Designing nanomaterials with desired mechanical properties by constraining the evolution of their grain shapes. AB - Grain shapes are acknowledged to impact nanomaterials' overall properties. Research works on this issue include grain-elongation and grain-strain measurements and their impacts on nanomaterials' mechanical properties. This paper proposes a stochastic model for grain strain undergoing severe plastic deformation. Most models deal with equivalent radii assuming that nanomaterials' grains are spherical. These models neglect true grain shapes. This paper also proposes a theoretical approach of extending existing models by considering grain shape distribution during stochastic design and modelling of nanomaterials' constituent structures and mechanical properties. This is achieved by introducing grain 'form'. Example 'forms' for 2-D and 3-D grains are proposed. From the definitions of form, strain and Hall-Petch-Relationship to Reversed-Hall-Petch Relationship, data obtained for nanomaterials' grain size and conventional materials' properties are sufficient for analysis. Proposed extended models are solved simultaneously and tested with grain growth data. It is shown that the nature of form evolution depends on form choice and dimensional space. Long-run results reveal that grain boundary migration process causes grains to become spherical, grain rotation coalescence makes them deviate away from becoming spherical and they initially deviate away from becoming spherical before converging into spherical ones due to the TOTAL process. Percentage deviations from spherical grains depend on dimensional space and form: 0% minimum and 100% maximum deviations were observed. It is shown that the plots for grain shape functions lie above the spherical (control) value of 1 in 2-D grains for all considered grain growth mechanisms. Some plots lie above the spherical value, and others approach the spherical value before deviating below it when dealing with 3 D grains. The physical interpretations of these variations are explained from elementary principles about the different grain growth mechanisms. It is observed that materials whose grains deviate further away from the spherical ones have more enhanced properties, while materials with spherical grains have lesser properties. It is observed that there exist critical states beyond which Hall Petch Relationship changes to Reversed Hall-Petch Relationship. It can be concluded that if grain shapes in nanomaterials are constrained in the way they evolve, then nanomaterials with desired properties can be designed. PMID- 22067061 TI - Coordinated increase of gamma-secretase reaction products in the plasma of some female Japanese sporadic Alzheimer's disease patients: quantitative analysis of p3-Alcalpha with a new ELISA system. AB - BACKGROUND: Aggregatable amyloid beta-peptide (Abeta) and non-aggregatable p3 Alcalpha are metabolic products of the gamma-secretase cleavage of amyloid beta protein precursor (APP) and Alcadeinalpha (Alcalpha), respectively. Familial AD (FAD) -linked mutations in the presenilin 1 or 2 (PS1 or PS2) component of gamma secretase can cause alternative intramembranous processing of APP and Alcalpha, leading to a coordinated generation of variants of both Abeta and p3-Alcalpha. Variant Alcalpha peptides have been observed in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment and sporadic Alzheimer's disease (AD). Since, like APP, Alcalpha is largely expressed in brain, one might predict that alternative processing of Alcalpha would be reflected in body fluids of some AD patients. These patients with misprocessing of multiple gamma-secretase substrates might define an endophenotype of p3-Alcalpha, in whom AD is due either to dysfunction of gamma-secretase or to a disorder of the clearance of hydrophobic peptides such as those derived from transmembrane domains. RESULTS: We developed a simple procedure for extraction of p3-Alcalpha from plasma and for analyzing this extract in a sensitive, p3-Alcalpha-specific sandwich enzyme linked immunosorbent assay (ELISA) system. Plasma p3-Alcalpha levels and Abeta40 levels were examined in sporadic AD subjects from two independent Japanese cohorts. In some of these patients, levels of plasma p3-Alcalpha were significantly higher, and were accompanied by parallel changes in Abeta40 levels. This AD-related difference was more marked in female subjects, but this phenomenon was not observed in subjects with frontotemporal lobar degeneration (FTLD). CONCLUSION: Reagents and procedures have been established that enable extraction of p3-Alcalpha from plasma and for quantification of plasma p3 Alcalpha levels by ELISA. Some populations of AD subjects apparently show increased levels of both p3-Alcalpha and Abeta40. Quantification of p3-Alcalpha level may be useful as a readily accessible biomarker for a population of sporadic AD patients in which disease pathogenesis is associated with either dysfunction of gamma-secretase or with a disorder of the clearance of transmembrane domain-derived peptides. PMID- 22067062 TI - Diastereoselective access to nonracemic 2-cis-substituted and 2,6-cis disubstituted piperidines. AB - Access to nonracemic amino ketones via a hydrozirconation/transmetalation/acylation sequence applied to Boc-protected 1 aminobut-3-enes is presented. This method was applied to the stereoselective synthesis of cyclic imines (or iminiums) which were diastereoselectively converted into 2-cis-substituted and 2,6-cis-disubstituted piperidines. The potential of this approach in the field of alkaloid synthesis was illustrated by the synthesis of (-)-coniine and (-)-indolizidine 209D. Furthermore, access to indolizidines bearing a quaternary center could also be envisioned through this strategy. PMID- 22067063 TI - Risk of second primary cancer after treatment for esophageal cancer: a pooled analysis of nine cancer registries. AB - The introduction of new treatments for esophageal cancer including surgery, chemotherapy, radiotherapy, or a combination of these modalities has not only improved patient survival, but may also increase the risk of the second primary cancers. The available evidence is conflicting with most risk estimates based on sparse numbers. Here we estimated standardized incidence ratios (SIRs) of second cancer among 24,557 esophageal cancer survivors (at least 2 months) in the Surveillance, Epidemiology, and End Results (SEER) Program between 1973 and 2007, who had been followed up for median 6.5 years (range 2 months-29.3 years). Second cancer risk was statistically significantly elevated (SIR = 1.34, 95% confidence interval [CI]= 1.25-1.42) among the survivors compared with the general population; the SIRs for cancers of oral and pharynx, stomach, small intestine, larynx, lung and bronchus, thyroid and prostate cancer were 8.64 (95% CI = 7.36 10.07), 2.87 (95% CI = 2.10-3.82), 3.80 (95% CI = 1.82-7.00), 3.19 (95% CI = 2.12 4.61), 1.68 (95% CI = 1.46-1.93), 2.50 (95% CI = 1.25-4.47), and 0.77 (95% CI = 0.65-0.90), respectively. Radiotherapy raised cancer risk of larynx (SIR = 3.98, 95% CI = 2.43-6.14) and thyroid (SIR = 3.57, 95% CI = 1.54-7.03) among all esophageal cancer survivors. For patients who had 5-9 years of follow up after radiotherapy, the SIR for lung cancer was 3.46 (95% CI = 2.41-4.82). Patients with esophageal cancer are at increased risks of second cancers of oral and pharynx, larynx, lung, and thyroid, while at a decreased risk for prostate cancer. These findings indicate that radiotherapy for esophageal cancer patients may increase risk of developing second cancers of larynx, lung, and thyroid. Thus, randomized clinical trials to address the association of radiotherapy and the risk of secondary cancer are warranted. PMID- 22067064 TI - Monitoring phytoplankton and marine biotoxins in production waters of the Netherlands: results after one decade. AB - Shellfish products may be contaminated with marine biotoxins which, after consumption, may lead to human illness. The Netherlands has a regular monitoring programme for marine biotoxins and the possible toxic phytoplankton in shellfish production waters. The aim of the current study was to evaluate the presence of potential toxic phytoplankton species and marine biotoxins in Dutch production waters over the last decade, and to analyse the relationship between toxin levels and abundance of possible causative phytoplankton species. The results of the monitoring programme of the period 1999-2009 were used. The presence of Alexandrium spp. were negligible, but Pseudo-nitzschia spp. and phytoplankton causing diarrhetic shellfish poisoning (DSP toxin-producing phytoplankton) were present in nearly all three main production areas and years. The main DSP toxin producing species was Dinophysis acuminata followed by D. rotundata and Prorocentrum lima. Toxins causing paralytic shellfish poisoning (PSP) and amnesic shellfish poisoning (ASP) were present in only a few individual shellfish samples, all at low levels. At the end of 2002, an episode of DSP toxicity was recorded, based on the rat bioassay results. Of the samples that were chemically analysed for DSP toxins in 2007 and 2008, about half of the samples in 2007 contained these toxins, although levels were low and no positive results were obtained using the rat bioassay. There was a slight positive correlation between concentrations of DSP toxin-producing phytoplankton and levels of DSP toxins in 2007. Increased DSP toxin levels were found up to 5 weeks after the peak in DSP toxin-producing phytoplankton. This positive, but weak, relationship needs to be confirmed in future research using more samples and chemical methods to quantify the presence of DSP toxins. If this relationship is further substantiated and quantified, it could be used within the current monitoring programme in the Netherlands to predict the risk areas regarding DSP toxicity in shellfish. PMID- 22067065 TI - Kawasaki disease in Jordan: demographics, presentation, and outcome. AB - Kawasaki disease is the leading cause of acquired coronary artery disease in young children. There is a lack of data on Kawasaki disease and its effect on coronary arteries in Jordan and other developing countries. We report clinical and demographic data of Kawasaki disease in Jordan from a single institution, with emphasis on cardiac involvement and short to intermediate follow-up. Review of the medical records of 34 patients with Kawasaki disease from 1997 to 2010 was done for clinical and demographic variables. Echocardiographic and angiographic images were reviewed for patients at presentation and follow-up. The median age at presentation was 19 months, ranging from 2 months to 8 years, with a male to female ratio of 3.9:1. In all, 12 patients (35%) had incomplete Kawasaki disease. There was a high incidence of coronary artery involvement (41%), where 20.5% had aneurysms and 20.5% had ectasia without aneurysm. Most coronary aneurysms were present at the time of diagnosis. The only independent variable for prediction of coronary involvement was age, with an odds ratio of 0.63 per year (95% confidence interval 0.41-0.95). PMID- 22067066 TI - A multilevel analysis of the determinants of high-risk sexual behaviour in sub Saharan Africa. AB - A number of authors have identified multiple concurrent sexual partnerships by both men and women to lie at the root of the HIV/AIDS epidemic in sub-Saharan Africa. This study applies multilevel models to Demographic and Health Survey data collected during 2003-2008 in 20 sub-Saharan African countries to examine the influence of social and cultural context on involvement with multiple sexual partnerships in the region, above and beyond the effects of individual characteristics. The findings provide support for the ecological argument that health behaviours are shaped and determined by societal conditions, in addition to the effects of individual and household characteristics. Involvement with multiple sex partners is most prevalent in societies in which sexual norms are widely permissive and where polygyny is common. Individual autonomy is substantial and attitudes towards sexuality are more liberal among men and women who live in communities in which sexual norms are widely permissive. Men and women who are most likely to have multiple sex partners in the sub-Saharan region are those who initiated sexual activity earlier and those who have the individual attributes (e.g. young age, urban residence, education, media exposure and working for cash and away from home) that bring to them more rights and/or decision-making autonomy, but not necessarily more financial resources and economic security (mostly among women). On the other hand, involvement with multiple partners is determined by cultural norms (i.e. permissive sexual norms) and social change (i.e. mass education, expansion of cash employment). The findings suggest a number of opportunities for more effective policy and programmatic responses to curb the prevalence of multiple partnerships in sub Saharan Africa. PMID- 22067067 TI - Pathology of the jaw: the importance of radiographs. AB - High-quality radiographs are essential in diagnosing pathology of the jaw. When appropriate radiographs are not submitted to the pathologist along with a biopsy specimen, misdiagnosis and mismanagement may occur. In this case study, we highlight the complementary value of panoramic and intraoral radiographs in allowing a definitive diagnosis of a mixed lesion of the jaw and preventing inappropriate treatment. Although many general dental practitioners tend to refer potential bony pathology, they should acquire and communicate high-quality radiographic information to specialty providers so that a precise diagnosis can be made. PMID- 22067068 TI - Esthetic rehabilitation of anterior teeth with porcelain laminates and sectional veneers. AB - Full-coverage bonded porcelain restorations offer predictable treatment options in dentistry, but a certain amount of tooth material must be removed to allow space for the required thickness of the restorative material. Laminate veneers and inlays are considered minimally invasive, but they also require removal of sound enamel. Sometimes, it may be preferable to extend the veneer preparations beyond the contact points toward the palatal surface, to hide the margins of the restoration, which necessitates removal of additional tissue. Improvements in adhesive technologies mean that small indirect restorations may be applied with removal of only a superficial layer of enamel. This clinical report describes a situation in which application of porcelain laminates and sectional veneers was chosen as the therapy of choice. A step-by-step protocol is proposed for cementation of these delicate restorations, and finishing procedures are described. PMID- 22067069 TI - Pre-exposure chemoprophylaxis of HIV infection: quo vadis? AB - The pre-exposure chemoprophylaxis (now commonly referred to as PrEP) of HIV infection has gained increased momentum, concomitantly with the successful use of combination drug regimens for the treatment of AIDS. A pivotal component in the current drug combination regimens for the treatment of AIDS as well as the ongoing PrEP trials is tenofovir disoproxil fumarate (TDF, Viread(r)) and its combination with emtricitabine (FTC). The combination of TDF with FTC has been marketed as Truvada(r). TDF and TDF/FTC has proven effective, if orally administered daily or intermittently, in the prevention of rectal simian human immunodeficiency virus (SHIV) infection in macaques. Topical tenofovir gel has proven effective in the prevention of HIV infection in women in South Africa. Oral TDF/FTC has proven effective in the prevention of HIV infection in men having sex with men, and recent press releases divulged that oral TDF/FTC is also effective in preventing HIV infection in serodiscordant couples in Botswana, Kenya and Uganda. Other PrEP studies are still ongoing. Available data point to the efficacy and safety of TDF with or without FTC in the prophylaxis of HIV infection (AIDS). PMID- 22067070 TI - Is size important? PMID- 22067071 TI - Antifouling coatings and ecological control in marinas. PMID- 22067072 TI - Genetic diversity of group A rotaviruses associated with repeated outbreaks of diarrhea in a farrow-to-finish farm: identification of a porcine rotavirus strain bearing a novel VP7 genotype, G26. AB - Group A rotaviruses (GARs) are one of the most common causes of diarrhea in suckling pigs. Although a number of G and P genotypes have been identified in porcine GARs, few attempts have been made to study the molecular epidemiology of these viruses associated with diarrhea outbreaks within a farm over an extended period of time. Here, we investigated the molecular characteristics of GARs that caused four outbreaks of diarrhea among suckling pigs in a farrow-to-finish farm over the course of a year. G and P genotyping of GARs detected at each outbreak demonstrated genetic diversity in this farm as follows: G9P[23] was detected at the first outbreak, G9P[13]/[22] and G9P[23] at the second, G3P[7] at the third, and G9P[23], G5P[13]/[22], and P[7] combined with an untypeable G genotype at the fourth. Sequence analysis of the detected GARs revealed that such genetic diversity could have resulted not only from the introduction of new GAR strains, but also from gene reassortment between GAR strains within the farm. Further, the GAR strain carrying the untypeable G genotype was shown to be a novel porcine GAR bearing a new G26 genotype, as confirmed by the Rotavirus Classification Working Group. PMID- 22067073 TI - Annual research review: conceptualising functional impairment in children and adolescents. AB - Functional impairment is a key factor in the clinical importance of mental health problems in children. Yet, the nature of impairment and criteria for defining and assessing impairment in childhood disorders has been surprisingly overlooked in much of the literature. The current article examines the extant literature on the conceptualisation, nature and assessment of impairment in childhood disorders. Relations between diagnostic symptoms and functional impairment are discussed together with the influence of impairment on diagnostic decisions and prevalence rates. Several factors influencing impairment in childhood such as culture, development and gender are considered. This article concludes with a discussion of the utility of separating judgements of impairment from specific diagnoses, which is proposed for consideration in the forthcoming DSM-5. PMID- 22067074 TI - What characterizes changing-state speech in affecting short-term memory? An EEG study on the irrelevant sound effect. AB - The irrelevant sound effect (ISE) describes reduced verbal short-term memory during irrelevant changing-state sounds which consist of different and distinct auditory tokens. Steady-state sounds lack such changing-state features and do not impair performance. An EEG experiment (N=16) explored the distinguishing neurophysiological aspects of detrimental changing-state speech (3-token sequence) compared to ineffective steady-state speech (1-token sequence) on serial recall performance. We analyzed evoked and induced activity related to the memory items as well as spectral activity during the retention phase. The main finding is that the behavioral sound effect was exclusively reflected by attenuated token-induced gamma activation most pronounced between 50-60 Hz and 50 100 ms post-stimulus onset. Changing-state speech seems to disrupt a behaviorally relevant ongoing process during target presentation (e.g., the serial binding of the items). PMID- 22067075 TI - Facile preparation of highly-dispersed cobalt-silicon mixed oxide nanosphere and its catalytic application in cyclohexane selective oxidation. AB - Highly dispersed cobalt-silicon mixed oxide [Co-SiO2] nanosphere was successfully prepared with a modified reverse-phase microemulsion method. This material was characterized in detail by X-ray diffraction, transmission electron microscopy, Fourier transform infrared, ultraviolet-visible diffuse reflectance spectra, X-ray absorption spectroscopy near-edge structure, and N2 adsorption desorption measurements. High valence state cobalt could be easily obtained without calcination, which is fascinating for the catalytic application for its strong oxidation ability. In the selective oxidation of cyclohexane, Co-SiO2 acted as an efficient catalyst, and good activity could be obtained under mild conditions. PMID- 22067076 TI - Combining immunolabeling and surface-enhanced Raman spectroscopy on cell membranes. AB - We applied surface-enhanced Raman spectroscopy (SERS) to immunolabeled endothelial cells to derive enhanced spectra of the biomolecular makeup of the cellular surface. A two-step immunolabeling protocol with gold-conjugated antibodies coupled with silver enhancement to attach silver nanoparticles to the cell surface was employed. This approach generated ~50-fold SERS enhancement of spectral signals. The SERS spectra exhibited several SERS-enhanced peaks associated with cell membrane components. The SERS detection of silver nanoparticles proved more far more sensitive than conventional light microscopy techniques. The SERS enhancement allowed us to carry out spectral mapping using wavenumbers associated with membrane components that correlated directly with the distribution of silver nanoparticles. SERS has the potential to detect immunolabeling at lower levels than is possible using conventional immunolabeling methods while simultaneously providing unique, spatially defined, biochemical information. PMID- 22067077 TI - Microbial diversity in deep-sea sediment from the cobalt-rich crust deposit region in the Pacific Ocean. AB - Cobalt-rich crusts are important metallic mineral resources with great economic potential, usually distributed on seamounts located in the Pacific Ocean. Microorganisms are believed to play a role in the formation of crusts as well as in metal cycling. To explore the microbial diversity related to cobalt-rich crusts, 16S ribosomal RNA gene clone libraries were constructed from three consecutive sediment layers. In total, 417 bacterial clones were obtained from three bacterial clone libraries, representing 17 distinct phylogenetic groups. Proteobacteria dominated in the bacterial communities, followed by Acidobacteria and Planctomycetes. Compared with high bacterial diversity, archaea showed a remarkably low diversity, with all 137 clones belonging to marine archaeal group I except one novel euryarchaeotal clone. The microbial communities were potentially involved in sulfur, nitrogen and metal cycling in the area of cobalt rich crusts. Sulfur oxidation and metal oxidation were potentially major sources of energy for this ecosystem. This is the first reported investigation of microbial diversity in sediments associated with cobalt-rich crusts, and it casts fresh light on the microbial ecology of these important ecosystems. PMID- 22067078 TI - Anesthesia of growing pigs with tiletamine-zolazepam and reversal with flumazenil. AB - The aim of the present study was to evaluate the anesthetic and cardiorespiratory effects of tiletamine/zolazepam and the effect of flumazenil on the recovery from tiletamine/zolazepam anesthesia in the pig. Six Landrace and Yorkshire cross-bred pigs (three females and three males, 3-4 months old) weighing 35.8 +/- 1.7 kg were used in this study. Pigs were given tiletamine/zolazepam intramuscularly at a dose of 4.4 mg kg(-1) (2.2 mg kg(-1) tiletamine and 2.2 mg kg(-1) zolazepam) of body weight. Twenty minutes after the administration of tiletamine/zolazem, the pigs were given saline solution (control, Group TZ) or given flumazenil intravenously at a dose of 0.08 mg kg(-1) of body weight (Group TZF). Anesthesia and recovery times, scores of anesthetic effects and cardiorespiratory variables were recorded for each pig. There was a significant difference between the duration of tiletamine/zolazepam anesthesia with and without the antagonist. Flumazenil significantly shortened the recovery time. A significant difference in blood gas variables was observed between the two groups. The anesthetic effects induced by tiletamine/zolazepam could be reversed successfully and safely by flumazenil alone. Therefore, flumazenil administration could be considered in cases in which quick recovery is required in pigs. PMID- 22067079 TI - Nicotinamide attenuates the decrease of astrocytic phosphoprotein PEA-15 in focal cerebral ischemic injury. AB - Nicotinamide exerts neuroprotective effects against focal cerebral ischemic injury. Phosphoprotein enriched in astrocytes 15 (PEA-15) is prominently expressed in astrocytes that exert broad anti-apoptotic functions. This study investigated whether nicotinamide modulates PEA-15 and levels of two phosphorylated PEA-15 (Serine 104 and 116) in an animal model of middle cerebral artery occlusion (MCAO)-induced injury. Adult male rats were treated with vehicle or nicotinamide (500 mg/kg) 2 hr after the onset of MCAO and cerebral cortices were collected at 24 hr after MCAO. In a proteomic approach, MCAO induced decreases of PEA-15 levels, while nicotinamide treatment attenuated the injury induced decrease in PEA-15. The results of Western blot analysis suggest that nicotinamide prevented injury-induced reduction in phospho-PEA-15 (Serine 104) and phospho-PEA-15 (Serine 116) levels. The phosphorylation of PEA-15 exerts anti apoptotic functions, and reduction of PEA-15 phosphorylation leads to apoptotic cell death. These results suggest that nicotinamide exerts a neuroprotective effect by attenuating the injury-induced decreases of PEA-15 and phospho-PEA-15 (Ser 104 and Ser 116) proteins. PMID- 22067080 TI - A case of renal oxalosis in a 3-month-old cat raised under controlled conditions. AB - The kidneys of a 3-month-old female cat were examined. The cat which had been raised under controlled conditions with no history of any poisoning showed progressive weight loss with increases in blood BUN and creatinine concentrations. At necropsy, both kidneys were firm in consistency with formation of focal scars. Histopathologically, widespread deposition of crystals was observed in the renal tubules (in both dilated lumina and degenerative epithelia) accompanying mild interstitial fibrosis with lymphocyte infiltration. The crystals were colorless or basophilic on the hematoxilin and eosin-stained section and could be visualized with polarized light as doubly fractile crystals. The crystals were identified as calcium oxalate crystals by histochemical examinations using von Kossa stain and alizarin red S stain under different conditions and by ultrastructural examination. Judging from the above-mentioned findings, the present renal lesion detected in an infant cat was diagnosed as renal oxalosis which was suspected to be hereditary in nature. PMID- 22067081 TI - A giant parovarian cyst in a dog with a granulosa cell tumor. AB - A 13-year old intact female poodle showed persistent signs of estrus. Ultrasonographically, a large cystic mass containing echogenic fluid with a thin wall was observed, and it was 8 cm in diameter. The cystic mass was located at the mesovarium between the left ovary and uterine horn, and it was identified as a giant parovarian cyst. A right ovarian mass was histologically diagnosed as a granulosa cell tumor. Persistent estrogen hormone secretion by the granulosa cell tumor was thought to cause a rapid increase in the size of the parovarian cyst. This rare cystic mass originated from the genital system and was differentiated from the uterus. PMID- 22067082 TI - Anatomic modifications in the enteric nervous system of JF1 mice with the classic piebald mutation. AB - The Japanese Fancy Mouse 1 (JF1) has a characteristic coat color similar to a very old mutant, piebald. The mutation in JF1 and the classic piebald was previously thought to be the same recessive allele in the endothelin B receptor gene (Ednrb) according to the haplotype pattern, which is insufficient for this conclusion. In this study, we identified the same insertion of a retroposon-like element in intron 1 of the Ednrb gene in JF1 as in the classic piebald mutation by PCR. Further, we investigated whether the intestine shows neuronal intestinal malformations such as hypoganglionosis and immaturity of ganglion cells by histochemical staining. Though it has been assumed that the defect of neural crest-derived lineages is restricted to melanocytes in JF1, we found that the enteric innervation and neuronal density were impaired throughout the whole colon in JF1 mice. PMID- 22067083 TI - Constructing stochastic models from deterministic process equations by propensity adjustment. AB - BACKGROUND: Gillespie's stochastic simulation algorithm (SSA) for chemical reactions admits three kinds of elementary processes, namely, mass action reactions of 0th, 1st or 2nd order. All other types of reaction processes, for instance those containing non-integer kinetic orders or following other types of kinetic laws, are assumed to be convertible to one of the three elementary kinds, so that SSA can validly be applied. However, the conversion to elementary reactions is often difficult, if not impossible. Within deterministic contexts, a strategy of model reduction is often used. Such a reduction simplifies the actual system of reactions by merging or approximating intermediate steps and omitting reactants such as transient complexes. It would be valuable to adopt a similar reduction strategy to stochastic modelling. Indeed, efforts have been devoted to manipulating the chemical master equation (CME) in order to achieve a proper propensity function for a reduced stochastic system. However, manipulations of CME are almost always complicated, and successes have been limited to relative simple cases. RESULTS: We propose a rather general strategy for converting a deterministic process model into a corresponding stochastic model and characterize the mathematical connections between the two. The deterministic framework is assumed to be a generalized mass action system and the stochastic analogue is in the format of the chemical master equation. The analysis identifies situations: where a direct conversion is valid; where internal noise affecting the system needs to be taken into account; and where the propensity function must be mathematically adjusted. The conversion from deterministic to stochastic models is illustrated with several representative examples, including reversible reactions with feedback controls, Michaelis-Menten enzyme kinetics, a genetic regulatory motif, and stochastic focusing. CONCLUSIONS: The construction of a stochastic model for a biochemical network requires the utilization of information associated with an equation-based model. The conversion strategy proposed here guides a model design process that ensures a valid transition between deterministic and stochastic models. PMID- 22067084 TI - Why California retailers stop selling tobacco products, and what their customers and employees think about it when they do: case studies. AB - BACKGROUND: In California, some 40,000 retailers sell tobacco products. Tobacco's ubiquitousness in retail settings normalizes use and cues smoking urges among former smokers and those attempting cessation. Thus, limiting the number of retailers is regarded as key to ending the tobacco epidemic. In the past decade, independent pharmacies and local grocery chains in California and elsewhere have voluntarily abandoned tobacco sales. No previous studies have examined the reasons for this emerging phenomenon. We sought to learn what motivated retailers to discontinue tobacco sales and what employees and customers thought about their decision. METHODS: We conducted case studies of seven California retailers (three grocery stores, four pharmacies) that had voluntarily ceased tobacco sales within the past 7 years. We interviewed owners, managers, and employees, conducted consumer focus groups, unobtrusively observed businesses and the surrounding environment, and examined any media coverage of each retailer's decision. We analyzed data using qualitative content analysis. RESULTS: For independent pharmacies, the only reason given for the decision to end tobacco sales was that tobacco caused disease and death. Grocers listed health among several factors, including regulatory pressures and wanting to be seen as "making a difference." Media coverage of stores' new policies was limited, and only three retailers alerted customers. Management reported few or no customer complaints and supportive or indifferent employees. Pharmacy employees were pleased to no longer be selling a deadly product. Grocery store management saw the decision to end tobacco sales as enhancing the stores' image and consistent with their inventory of healthy foods. Focus group participants (smokers and nonsmokers) were largely unaware that retailers had stopped selling tobacco; however, almost all supported the decision, viewing it as promoting public health. Many said knowing this made them more likely to shop at the store. Most thought that advertising the store's policy was essential to generate good public relations and tobacco norm changes. CONCLUSIONS: Voluntary retailer abandonment of tobacco sales both reflects and extends social norm changes that have problematized tobacco in California. Our findings suggest that such voluntary initiatives by retailers are welcomed by consumers and should be publicized, enhancing public health efforts. PMID- 22067085 TI - The sequences of groESL operon of Anaplasma phagocytophilum among human patients in Slovenia. AB - Anaplasma phagocytophilum is an emerging tick-borne pathogen. Great genetic diversity of A. phagocytophilum has been described in animals and ticks. The present study is focused on the genetic variability of the groESL operon of A. phagocytophilum in human patients in Slovenia. During 1996-2008, there were 66 serologically confirmed patients with human granulocytic anaplasmosis. Of these, 46 were tested with a screening PCR for a small part of the 16S rRNA gene of A. phagocytophilum and 28 (60.9%) were positive. Positive samples were additionally tested with a PCR targeting the groESL operon and a larger fragment of the 16S rRNA gene. All amplicons were further sequenced and analyzed. The homology search and the alignment of the groESL sequences showed only one genetic variant. Sequence analysis of the 16S rRNA gene revealed 100% identity among amplicons. Slovenia is a small country with diverse climate, vegetation, and animal representatives. In previous studies in deer, dogs, and ticks, great diversity of the groESL operon was found. In contrast, in wild boar and in human patients from this study, only one genetic variant was detected. The results suggest that only one genetic variant might be pathogenic for humans or is competent enough to replicate in humans. To support this theory, other genetic markers and further studies need to be performed. PMID- 22067086 TI - Management of patients with transient ischemic attack is safe in an outpatient clinic based on rapid diagnosis and risk stratification. AB - BACKGROUND: Transient ischemic attack (TIA) patients are at high risk of short term stroke, myocardial infarction and vascular death. Stroke risk is reduced by immediate treatment initialization. Stroke unit treatment is recommended for TIA patients. We established an outpatient TIA clinic to address the question whether outpatient evaluation of suspected TIA is safe. METHODS: TIA workup included cerebral imaging, duplex sonography, transcranial Doppler screening for patent foramen ovale, electrocardiography, blood tests, ABCD(2) score and ankle-brachial index within one day. TIA patients received secondary prophylaxis immediately. TIA patients fulfilling predefined criteria for high early stroke risk (ABCD(2) score >=4 points and TIA within 72 h, symptomatic stenosis, newly detected atrial fibrillation, recurrent TIA) were referred to the stroke unit. The remaining patients were discharged home. 90-day telephone follow-up was obtained. RESULTS: 123 consecutive patients with suspected TIA (53 male, age 59 +/- 17.2 years) were prospectively evaluated. TIA or minor stroke was diagnosed in 69 (56%), and TIA mimics in 54 (44%) patients. Median time from symptom onset to presentation was 48 h (1 h to 3 months). Patients with TIA/minor stroke presented significantly more frequently with ABCD(2) score >=4 points (p = 0.021). Twelve patients (9.8%) were admitted to the stroke unit. There were 2 strokes during follow-up. The stroke rate was 1.6% within all patients, and 2.9% within the subgroup of patients with TIA/minor stroke, compared to 5.7% predicted by the ABCD(2) score. Other vascular end points were not found. CONCLUSION: Based on risk stratification, outpatient evaluation of TIA is safe. TIA mimics are frequent. PMID- 22067087 TI - A presumably benign human ether-a-go-go-related gene mutation (R176W) with a malignant primary manifestation of long QT syndrome. AB - A 12-year-old girl presented with a first prolonged syncope. She was successfully resuscitated by external defibrillation after recording torsade de pointes tachycardia. Repeated electrocardiograms and a 12-channel Holter monitoring showed an intermittent prolongation of the QT interval. Genetic analysis identified a heterozygous point mutation in the KCNH2 gene, which is thought to be associated with a rather mild clinical phenotype of the long QT syndrome. PMID- 22067088 TI - HER2 status in unusual histological variants of gastric adenocarcinomas. AB - AIM: To investigate HER2 status in a cohort of 109 gastric adenocarcinomas also including unusual variants, such as 14 hepatoid (HAS) and 9 mitochondrion-rich (MRC), characterised by an opposing clinical behaviour. METHODS AND RESULTS: Using HercepTest (DAKO) and FISH test (pharmDx DAKO), HER2 overexpression/amplification was encountered in 23 of 109 (21.10%) of all gastric adenocarcinomas. A progressive increase in HER2 overexpression was observed moving from the poorly cohesive histotype to MRC, tubular adenocarcinomas and HAS. A statistically significant difference was found between poorly cohesive carcinomas and the others; a similar significant difference was encountered between HAS and all other variants of adenocarcinoma. HER2 overexpression was significantly associated with high grade, advanced stage, high Ki-67 labelling index value and death from gastric cancer. Multivariate analysis identified HER2 overexpression as an independent unfavourable prognostic variable for adenocarcinomas as a whole and also for the HAS variant. CONCLUSIONS: Trastuzumab has been confirmed as an additional useful therapeutic standard option for patients with HER2-positive advanced gastric cancers, and also in aggressive variants of adenocarcinomas such as HAS. PMID- 22067089 TI - End-of-life preferences of elderly patients with chronic heart failure. AB - AIMS: Elderly heart failure (HF) patients are assumed to prefer improved quality of life over longevity, but sufficient data are lacking. Therefore, we assessed the willingness to trade survival time for quality-of-life (QoL) and the preferences for resuscitation. METHODS AND RESULTS: At baseline and after 12 and 18 months, 622 HF patients aged >=60 years (77 +/- 8 years, 74% NYHA-class >=III) participating in the Trial of Intensified vs. standard Medical therapy in Elderly patients with Congestive Heart Failure had prospective evaluation of end-of-life preferences by answering trade-off questions (willingness to accept a shorter life span in return for living without symptoms) and preferences for resuscitation if necessary. The time trade-off question was answered by 555 patients (89%), 74% of whom were not willing to trade survival time for improved QoL. This proportion increased over time (Month 12: 85%, Month 18: 87%, P < 0.001). In multivariable analysis, willingness to trade survival time increased with age, female sex, a reduced Duke Activity Status Index, Geriatric Depression Score, and history of gout, exercise intolerance, constipation and oedema, but even combining these variables did not result in reliable prediction. Of 603 (97%) patients expressing their resuscitation preference, 51% wished resuscitation, 39% did not, and 10% were undecided, with little changes over time. In 430 patients resuscitation orders were known; they differed from patients' preferences 32% of the time. End-of-life preferences were not correlated to 18-month outcome. CONCLUSION: Elderly HF patients are willing to address their end-of-life preferences. The majority prefers longevity over QoL and half wished resuscitation if necessary. Prediction of individual preferences was inaccurate. PMID- 22067090 TI - High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study. AB - AIMS: The aim of this study was to compare on-thienopyridine platelet reactivity of elderly patients (>=75 years) vs. younger patients (<75 years). Elderly patients represent a growing and challenging segment of the coronary population for whom the effect of dual antiplatelet therapy on platelet inhibition has not been specifically addressed. METHODS AND RESULTS: The SENIOR-PLATELET study included 1331 coronary patients chronically (>14 days) treated with aspirin and a thienopyridine (clopidogrel 75 mg, n= 1027; clopidogrel 150 mg, n= 139; or prasugrel 10 mg, n= 165). Platelet response to clopidogrel and prasugrel was assessed by the VerifyNow assay and light transmission aggregrometry (LTA). Response to treatment, rate of high platelet reactivity (HPR), and inhibition (HPI) were compared in the two age categories. On-treatment platelet reactivity with clopidogrel 75 mg, 150 mg or prasugrel 10 mg was higher in elderly patients (n= 205) than in younger patients (n= 1126) whichever the test used. The difference in P2Y(12) reaction units (PRU) between the two populations was +45 in patients treated with clopidogrel 75 mg (P< 0.0001), +30 in patients treated with clopidogrel 150 mg (P= 0.17), and +20 with prasugrel 10 mg (P= 0.10). Differences in residual platelet aggregation were consistent when measured by LTA. Elderly patients treated with clopidogrel 75 mg were more likely to have HPR than younger patients (38.2 vs. 18.2%, OR: 2.58, 95% CI: 1.76-3.79; P< 0.0001) even after adjustment for potential confounders (adj OR: 1.83, 95% CI: 1.16-2.87; P= 0.009). CONCLUSION: Elderly patients present an impaired response to clopidogrel with a high rate of HPR. Clopidogrel 150 mg or prasugrel 10 mg blunt, but do not eliminate the difference in response observed between old and young patients. PMID- 22067091 TI - Coagulase-negative staphylococci from non-mastitic bovine mammary gland: characterization of Staphylococcus chromogenes and Staphylococcus haemolyticus by antibiotic susceptibility testing and pulsed-field gel electrophoresis. AB - During routine microbiological examination of milk samples from dairy cows without clinical signs of mastitis, quarter milk samples of 231 dairy cows from 12 herds were investigated for the presence of coagulase-negative staphylococci (CNS). The isolates were identified on the basis of colony morphology, Gram staining, catalase and coagulase test and the commercial kit, API Staph. CNS was detected in 29% (67/231) of the cows. A total of seven CNS species were identified with the most prevalent being Staphylococcus (Staph.) chromogenes (30%) and Staph. haemolyticus (28.8%), followed by Staph. simulans (11.2%), Staph. xylosus (11.2%), Staph. epidermidis (7.5%), Staph. hyicus (6.3%) and Staph. sciuri (5%). The predominant species, Staph. chromogenes and Staph. haemolyticus, were further characterized by antibiotic susceptibility testing using the agar disc diffusion method (Kirby-Bauer) and by pulsed-field gel electrophoresis (PFGE). Considerable resistance to ampicillin and penicillin was observed in both species. Isolates with identical or highly similar PFGE profiles were detected at the herd level despite a marked heterogeneity seen for both species. On the basis of somatic cell count, absence of clinical signs of inflammation and heterogeneity of genotypes, we assume that CNS isolated in this study could not be considered as important causative agents of the bovine mammary gland inflammation. PMID- 22067092 TI - Efavirenz interference in urine screening immunoassays for tetrahydrocannabinol. AB - BACKGROUND: It has been known for some time that the antiretroviral drug, efavirenz (EFV), cross-reacts in urine immunoassays for tetrahydrocannabinol (THC). Because published studies investigating this phenomenon are limited, cross reactivity information for several immunoassays is lacking. Reports of possible false-positive THC results from clinicians conducting workplace testing prompted us to investigate cross-reactivity for assays frequently employed in our own setting. In light of the potentially deleterious consequences of misclassification, information about EFV cross-reactivity should be included in product information to facilitate interpretation of results and assay selection. METHODS: Random urine samples from 30 patients on EFV therapy were analysed for THC metabolites by two near-testing devices (THC One Step Marijuana and Rapid Response((r)) Drugs of Abuse Test Strips) and two automated immunoassays (Roche Diagnostics Cannabinoids II and Beckman Coulter SYNCHRON((r)) Systems THC2). THC confirmatory testing was performed by gas chromatography-mass spectrometry (GC MS). RESULTS: GC-MS failed to detect THC metabolites in any of the samples, as did three of the four immunoassays. However, the Rapid Response((r)) test strips yielded positive results in 28 out of 30 samples, which could be reversed on re testing after sample pretreatment with glucuronidase. CONCLUSIONS: Our study supports previous findings that interference is attributable to a glucuronidated EFV metabolite. We postulate that cross-reactivity is influenced by the composition of immunogens used to elicit anti-THC antibodies. Since access to such information is restricted, contributions from scientists in the antibody industry may be enlightening. PMID- 22067093 TI - Seasonal pseudohyperkalaemia: no longer an issue? AB - BACKGROUND: Spurious hyperkalaemia is a well-recognized problem when reporting potassium results in samples originating from Primary Care. This is particularly relevant in laboratories serving large geographical areas where sample transport can cause significant delays in sample centrifugation. We have carried out a retrospective audit comparing serum potassium results on samples centrifuged at the general practice (GP) with those centrifuged on arrival at the clinical laboratory. METHODS: Potassium results were reviewed on serum samples received from 87 GPs in the Grampian region between August 2010 and March 2011. Potassium results were compared between samples centrifuged at the practice versus those centrifuged on arrival at the clinical laboratory. RESULTS: In the period between November 2010 and February 2011, median monthly serum potassium results were significantly different between samples centrifuged at practices and those centrifuged on arrival at the laboratory. Median potassium concentrations were 10.2% higher in January 2011 (4.8 mmol/L; interquartile range [IQR]: 4.5-5.1) compared with August 2010 (4.3 mmol/L; IQR: 4.0-4.6). A similar trend in monthly median potassium concentrations was not evident in samples centrifuged at source over the same period. CONCLUSIONS: The introduction of centrifuges into all GPs across NHS Grampian has significantly reduced the effect of seasonal variation in serum potassium results. There has also been a concurrent reduction in the number of cases of spurious hyperkalaemia. This exercise has significantly improved the overall quality of potassium results reported to Primary Care. PMID- 22067095 TI - Circumpolar health collaborations: a description of players and a call for further dialogue. PMID- 22067096 TI - Suicide and alcohol-related disorders in the U.S. Arctic: boosting research to address a primary determinant of health disparities. AB - OBJECTIVES: To review the existing epidemiological literature on suicide and alcohol-related disorders and their social determinants in the U.S. Arctic, as it relates to U.S. government research and evaluation efforts, and to offer recommendations to boost research capacity in the U.S. Arctic and collaborations across the circumpolar Arctic as part of global health initiatives. STUDY DESIGN: Synthetic literature review. METHODS: Published literature; federal and state reports on suicide and alcohol-related disorders; and federal databases on research and program evaluation in the U.S Arctic were reviewed, with a focus on epidemiological trends over the past 50 years. RESULTS: Suicide and alcohol related disorders play a significant role in health disparities in the U.S. Arctic, with evidence of a disturbing prevalence trend over the past 50 years. Important variations exist in suicide rates across different regions of Alaska with different majority populations of Alaska Native cultural groups - and, in selected key instances, within these regions - with immense implications for guiding effective prevention efforts. Consequences of alcohol abuse are severe and particularly significant in their impact upon Alaska Native people. Health related conditions associated with alcohol abuse are among the leading causes of mortality. CONCLUSIONS: Recommendations to boost research capacity in behavioural health in the U.S. Arctic are offered, specifically on strategies and methods of inquiry and analysis; distinctions between populations and communities in rural circumpolar contexts; and future epidemiological and implementation research. PMID- 22067097 TI - Providers' perceptions of barriers to the management of type 2 diabetes in remote Aboriginal settings. AB - OBJECTIVES: To examine providers' perspectives of the barriers to providing diabetes care in remote First Nation communities in the Sioux Lookout Zone (SLZ) of Northwestern Ontario, Canada. STUDY DESIGN: A qualitative study involving key informant interviews and focus groups was conducted with health care providers working in remote First Nation communities in SLZ. METHODS: Twenty-four nurses, doctors, diabetes educators and community health representatives (CHRs) participated in qualitative interviews and focus groups. Data collected from the interviews and focus groups was coded and thematically analysed using NVIVO software. RESULTS: Barriers to diabetes care were grouped into patient, clinic and system factors. Providers' perceptions of patient factors were divided between those advocating for a patient-provider partnership and those advocating for greater patient responsibility. Clinic-related barriers such as short staffing, staff turnover and system fragmentation were discussed, but were often overshadowed by a focus on patient factors and a general sense of frustration among providers. Cultural awareness and issues with clinic management were not mentioned, though they are both within the providers' control. CONCLUSIONS: This study characterizes a range of barriers to diabetes care and shows that patient related factors are of primary concern for many providers. We conclude that patient-focused interventions and cultural competence training may help improve patient-provider partnerships. Funding and supporting quality improvement initiatives and clinic reorganization may increase the providers' knowledge of the potential for clinical strategies to improve patient outcomes and focus attention on those factors that providers can change. Future research into the factors driving quality of care and strategies that can improve care in Aboriginal communities should be a high priority in addressing the rising burden of diabetes and related complications. PMID- 22067098 TI - ApoptoProteomics, an integrated database for analysis of proteomics data obtained from apoptotic cells. AB - Apoptosis is the most commonly described form of programmed cell death, and dysfunction is implicated in a large number of human diseases. Many quantitative proteome analyses of apoptosis have been performed to gain insight in proteins involved in the process. This resulted in large and complex data sets that are difficult to evaluate. Therefore, we developed the ApoptoProteomics database for storage, browsing, and analysis of the outcome of large scale proteome analyses of apoptosis derived from human, mouse, and rat. The proteomics data of 52 publications were integrated and unified with protein annotations from UniProt KB, the caspase substrate database homepage (CASBAH), and gene ontology. Currently, more than 2300 records of more than 1500 unique proteins were included, covering a large proportion of the core signaling pathways of apoptosis. Analysis of the data set revealed a high level of agreement between the reported changes in directionality reported in proteomics studies and expected apoptosis-related function and may disclose proteins without a current recognized involvement in apoptosis based on gene ontology. Comparison between induction of apoptosis by the intrinsic and the extrinsic apoptotic signaling pathway revealed slight differences. Furthermore, proteomics has significantly contributed to the field of apoptosis in identifying hundreds of caspase substrates. The database is available at http://apoptoproteomics.uio.no. PMID- 22067099 TI - Extending the dynamic range of label-free mass spectrometric quantification of affinity purifications. AB - Affinity purification (AP) of protein complexes combined with LC-MS/MS analysis is the current method of choice for identification of protein-protein interactions. Their interpretation with respect to significance, specificity, and selectivity requires quantification methods coping with enrichment factors of more than 1000-fold, variable amounts of total protein, and low abundant, unlabeled samples. We used standardized samples (0.1-1000 fmol) measured on high resolution hybrid linear ion trap instruments (LTQ-FT/Orbitrap) to characterize and improve linearity and dynamic range of label-free approaches. Quantification based on spectral counts was limited by saturation and ion suppression effects with samples exceeding 100 ng of protein, depending on the instrument setup. In contrast, signal intensities of peptides (peak volumes) selected by a novel correlation-based method (TopCorr-PV) were linear over at least 4 orders of magnitude and allowed for accurate relative quantification of standard proteins spiked into a complex protein background. Application of this procedure to APs of the voltage-gated potassium channel Kv1.1 as a model membrane protein complex unambiguously identified the whole set of known interaction partners together with novel candidates. In addition to discriminating these proteins from background, we could determine efficiency, cross-reactivities, and selection biases of the used purification antibodies. The enhanced dynamic range of the developed quantification procedure appears well suited for sensitive identification of specific protein-protein interactions, detection of antibody related artifacts, and optimization of AP conditions. PMID- 22067100 TI - An integrated chemical cross-linking and mass spectrometry approach to study protein complex architecture and function. AB - Knowledge of protein structures and protein-protein interactions is essential for understanding biological processes. Chemical cross-linking combined with mass spectrometry is an attractive approach for studying protein-protein interactions and protein structure, but to date its use has been limited largely by low yields of informative cross-links (because of inefficient cross-linking reactions) and by the difficulty of confidently identifying the sequences of cross-linked peptide pairs from their fragmentation spectra. Here we present an approach based on a new MS labile cross-linking reagent, BDRG (biotin-aspartate-Rink-glycine), which addresses these issues. BDRG incorporates a biotin handle (for enrichment of cross-linked peptides prior to MS analysis), two pentafluorophenyl ester groups that react with peptide amines, and a labile Rink-based bond between the pentafluorophenyl groups that allows cross-linked peptides to be separated during MS and confidently identified by database searching of their fragmentation spectra. We developed a protocol for the identification of BDRG cross-linked peptides derived from purified or partially purified protein complexes, including software to aid in the identification of different classes of cross-linker modified peptides. Importantly, our approach permits the use of high accuracy precursor mass measurements to verify the database search results. We demonstrate the utility of the approach by applying it to purified yeast TFIIE, a heterodimeric transcription factor complex, and to a single-step affinity purified preparation of the 12-subunit RNA polymerase II complex. The results show that the method is effective at identifying cross-linked peptides derived from purified and partially purified protein complexes and provides complementary information to that from other structural approaches. As such, it is an attractive approach to study the topology of protein complexes. PMID- 22067101 TI - Aluminum alters NMDA receptor 1A and 2A/B expression on neonatal hippocampal neurons in rats. AB - BACKGROUND: High aluminum (Al) content in certain infant formula raises the concern of possible Al toxicity on brain development of neonates during their vulnerable period of growing. Results of in vivo study showed that Al content of brain tissues reached to 74 MUM when oral intake up to 1110 MUM, 10 times of that in the hi-Al infant formula. METHODS: Utilizing a cultured neuron cells in vitro model, we have assessed Al influence on neuronal specific gene expression alteration by immunoblot and immunohistochemistry and neural proliferation rate changes by MTT assay. RESULTS: Microscopic images showed that the neurite outgrowth of hippocampal neurons increased along with the Al dosages (37, 74 MUM Al (AlCl3)). MTT results also indicated that Al increased neural cell viability. On the other hand, the immunocytochemistry staining suggested that the protein expressions of NMDAR 1A and NMDAR 2A/B decreased with the Al dosages (p < 0.05). CONCLUSION: Treated hippocampal neurons with 37 and 74 MUM of Al for 14 days increased neural cell viability, but hampered NMDAR 1A and NMDAR 2A/B expressions. It was suggested that Al exposure might alter the development of hippocampal neurons in neonatal rats. PMID- 22067102 TI - Insulin detemir in a twice daily insulin regimen versus a three times daily insulin regimen in the treatment of type 1 diabetes in children: A pilot randomized controlled trial. AB - BACKGROUND: Children with type 1 diabetes (DM1) often use three daily (TID) injections with intermediate acting insulin at breakfast and bedtime, and rapid acting insulin at breakfast and dinner. Substituting the evening intermediate acting insulin with a long acting insulin analogue (LAIA) at dinner in a twice daily (BID) injection regimen may be as effective as a TID regimen. The objective of this pilot study was to compare HbA1c in children with DM1 using a BID regimen with a LAIA at dinner (intervention) to those using a standard TID regimen (control) over 6 months. METHODS: Randomized controlled trial with main outcome measure being HbA1c at 0, 3 and 6 months. Secondary outcomes were frequency of adverse events (hypoglycemia, diabetic ketoacidosis, weight gain) and scores on the Diabetes Quality of Life Measure for Youth (DQOLY). RESULTS: 18 subjects (10 control, 8 intervention). Mean years (standard deviations) for control and intervention respectively were: age at diagnosis of DM1 6.31 (2.91) vs 7.76 (3.22), duration of DM1 5.96 (4.95) vs 3.76 (3.37). No significant differences were seen in the mean HbA1c between control and intervention at 0 months [8.48(0.86) vs 8.57(1.13)], 3 months [8.47(0.50) vs 7.99(0.61)], or 6 months [8.42(0.63) vs 8.30(0.76)]. No significant differences were found between groups for frequency of adverse events or DQOLY. CONCLUSIONS: In this pilot study, incorporating LAIA in a BID regimen did not cause deterioration in HbA1c or increases in adverse events; suggesting that this may be a viable option for families where a more simplified insulin regimen would be beneficial and compliance may be improved. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00522210. PMID- 22067103 TI - Long-term follow-up after lamellar keratoplasty in a patient with bilateral idiopathic corneal keloid. AB - PURPOSE: To report a case of bilateral idiopathic corneal keloid. METHODS: Retrospective review of clinical features, histopathological findings, clinical management, and outcome. RESULTS: A 2-year-old boy with bilateral corneal keloid was treated with lamellar keratoplasty and tranilast eye drops. Peripheral localized white corneal nodules had been present bilaterally since the age of approximately 6 months in the absence of any history of trauma, inflammatory disease, or relevant family history. Pathological examination of the excised corneal buttons revealed myofibroblast proliferation (positive staining for alpha smooth muscle actins), a haphazard arrangement of collagen bundles, and the absence of inflammatory cells. On the basis of these findings, a diagnosis of corneal keloid was assigned. The size of the corneal lesion in the right eye decreased in response to therapy with tranilast eye drops. Lamellar keratoplasty resulted in improved bilateral visual acuity, which was maintained at the 12-year follow-up. CONCLUSIONS: This report describes a very rare case of bilateral corneal keloid in the absence of trauma or inflammation that was diagnosed by histological and immunohistochemical examination and electron microscopy. Good visual acuity was maintained over an extended period of postsurgery follow-up. Tranilast may represent a novel adjuvant therapy for corneal keloid. PMID- 22067104 TI - Superoxide radical production and performance index of Photosystem II in leaves from magnetoprimed soybean seeds. AB - Priming of soybean seeds with static magnetic field exposure of 200 mT (1 h) and 150 mT (1 h) resulted in plants with enhanced performance index (PI). The three components of PI i.e the density of reaction centers in the chlorophyll bed (RC/ABS), exciton trapped per photon absorbed (phipo) and efficiency with which a trapped exciton can move in electron transport chain (Psio) were found to be 17%, 27% and 16% higher, respectively in leaves from 200 mT (1h) treated compared to untreated seeds. EPR spectrum of O2.--PBN adduct revealed that the O2.-radical level was lower by 16% in the leaves of plants that emerged from magnetic field treatment. Our study revealed that magnetoprimed seeds have a long lasting stimulatory effect on plants as reduced superoxide production and higher performance index contributed to higher efficiency of light harvesting that consequently increased biomass in plants that emerged from magnetoprimed seeds. PMID- 22067105 TI - Genetic regulation of life cycle transitions in the brown alga Ectocarpus. AB - The life cycle of an organism is one of its most elemental features, underpinning a broad range of phenomena including developmental processes, reproductive fitness, mode of dispersal and adaptation to the local environment. Life cycle modification may have played an important role during the evolution of several eukaryotic groups, including the terrestrial plants. Brown algae are potentially interesting models to study life cycle evolution because this group exhibits a broad range of different life cycles. Currently, life cycle studies are focused on the emerging brown algal model Ectocarpus. Two life cycle mutants have been described in this species, both of which cause the sporophyte generation to exhibit gametophyte characteristics. The ouroboros mutation is particularly interesting because it induces complete conversion of the sporophyte generation into a functional, gamete-producing gametophyte, a class of mutation that has not been described so far in other systems. Analysis of Ectocarpus life cycle mutants is providing insights into several life-cycle-related processes including parthenogenesis, symmetric/asymmetric initial cell divisions and sex determination. PMID- 22067106 TI - Fearful symmetry in aposematic plants. AB - Symmetry has been proposed to increase the efficiency of visual aposematic displays in animals, and I suggest that it may also be true for many aposematic spiny or poisonous plants. For instance, in the very spiny plant taxa cacti, Aloe sp., Agave sp. and Euphorbia sp., which have been proposed to be aposematic because of their colorful spine system, the shoots, and in cacti, the spiny fruits as well, are usually radially symmetric. Moreover, in the radial symmetric shoots of Agave and Aloe their individual spiny leaves are also bilaterally symmetric. Spiny or poisonous fruits of various other taxa, the symmetric spiny leaf rosettes and flowering spiny heads of many Near Eastern species of the Asteraceae and other taxa, and poisonous colorful flowers in taxa that were proposed to be aposematic are also symmetric. Thus, in plants, like in animals, symmetry seems to be commonly associated with visual aposematism and probably contributes to its effectiveness. Symmetry may stem from developmental constraints, or like in flowers, have other signaling functions. However, because of the better perception of symmetry by animals it may exploit inherited modes of animal sensing that probably result in paying more attention to symmetric shapes. All these possible alternatives do not negate the probable deterring role of symmetry in plant aposematism. PMID- 22067107 TI - Strategy for shoot meristem proliferation in plants. AB - Shoot apical meristem (SAM) of plants harbors stem cells capable of generating the aerial tissues including reproductive organs. Therefore, it is very important for plants to control SAM proliferation and its density as a survival strategy. The SAM is regulated by the dynamics of a specific gene network, such as the WUS CLV interaction of A. thaliana. By using a mathematical model, we previously proposed six possible SAM patterns in terms of the manner and frequency of stem cell proliferation. Two of these SAM patterns are predicted to generate either dichotomous or axillary shoot branch. Dichotomous shoot branches caused by this mechanism are characteristic of the earliest vascular plants, such as Cooksonia and Rhynia, but are observed in only a small minority of plant species of the present day. On the other hand, axillary branches are observed in the majority of plant species and are induced by a different dynamics of the feedback regulation between auxin and the asymmetric distribution of PIN auxin efflux carriers. During evolution, some plants may have adopted this auxin-PIN system to more strictly control SAM proliferation. PMID- 22067108 TI - Basic helix-loop-helix transcription factors and regulation of alkaloid biosynthesis. AB - Transcription factors of the basic Helix-Loop-Helix (bHLH) family play a central role in cell proliferation, determination, and differentiation. In plants, the regulatory functions of bHLHs in phenylpropanoid biosynthesis have been well established with regard to other interacting-proteins; i.e., MYB and WD40 repeat proteins. On the other hand, those in alkaloid biosynthesis are greatly limited due to the limited distribution of alkaloids in plant species. Recently, several groups have reported the regulatory functions of bHLH in alkaloid biosynthesis: novel CjbHLH1 in isoquinoline alkaloid biosynthesis in Coptis japonica, and Jasmonate-inducible MYC2-type bHLHs in nicotine-alkaloid biosynthesis in Nicotiana plants and indole alkaloid biosynthesis in Catharanthus roseus. We report here the JA-inducibility of CjbHLH1 and discuss the similarity and differences of non-MYC2-resemblant CjbHLH1 and MYC2-type bHLHs in nicotine and indole alkaloid biosynthesis. PMID- 22067109 TI - Role of the iron transporter OsNRAMP1 in cadmium uptake and accumulation in rice. AB - The heavy metal cadmium (Cd) is toxic to humans, and its accumulation in rice grains is a major agricultural problem. Rice has seven putative metal transporter NRAMP genes, but microarray analysis showed that only OsNRAMP1 is highly up regulated by iron (Fe) deficiency. OsNRAMP1 localized to the plasma membrane and transported Cd as well as Fe. OsNRAMP1 expression was observed mainly in roots and was higher in the roots of a high-Cd-accumulating cultivar (Habataki) than in those of a low-Cd-accumulating cultivar (Sasanishiki). The amino acid sequence of OsNRAMP1 in the Sasanishiki and Habataki cultivars was found to be 100% identical. These results suggest that OsNRAMP1 participates in cellular Cd uptake and that the differences observed in Cd accumulation among cultivars are because of differences in OsNRAMP1 expression levels in roots. PMID- 22067110 TI - Phytochrome A-specific signaling in Arabidopsis thaliana. AB - Among the five phytochromes in Arabidopsis thaliana, phytochrome A (phyA) plays a major role in seedling de-etiolation. Until now more then ten positive and some negative components acting downstream of phyA have been identified. However, their site of action and hierarchical relationships are not completely understood yet. PMID- 22067111 TI - Multistrand RNA secondary structure prediction and nanostructure design including pseudoknots. AB - We are presenting NanoFolder, a method for the prediction of the base pairing of potentially pseudoknotted multistrand RNA nanostructures. We show that the method outperforms several other structure prediction methods when applied to RNA complexes with non-nested base pairs. We extended this secondary structure prediction capability to allow RNA sequence design. Using native PAGE, we experimentally confirm that four in silico designed RNA strands corresponding to a triangular RNA structure form the expected stable complex. PMID- 22067112 TI - Reduced carbohydrate diet to improve metabolic outcomes and decrease adiposity in obese peripubertal African American girls. AB - OBJECTIVE: Obesity prevalence among African American (AA) girls is higher than that in other groups. Because typical energy-restriction obesity treatment strategies have had limited success, alterations in macronutrient composition may effectively improve metabolic outcomes in this population and affect future body composition trajectories. The objective was to evaluate the efficacy of a moderately restricted carbohydrate (CHO) versus a standard CHO diet on weight/fat loss and metabolic parameters in overweight/obese AA girls ages 9 to 14 years. METHODS: A total of 26 AA girls (ranging from 92nd body mass index percentile and above) were assigned to either a reduced- (SPEC: 42% energy from CHO, n = 12) or a standard- (STAN: 55% of energy from CHO, n = 14) CHO diet (protein held constant) for 16 weeks. All of the meals were provided and clinically tailored to meet the estimated energy requirements (resting energy expenditure * 1.2 in eucaloric phase and resting energy expenditure * 1.2 - 1000 kcal in energy deficit phase). The first 5 weeks encompassed a eucaloric phase evaluating metabolic changes in the absence of weight change. The subsequent 11 weeks were hypocaloric (1000 kcal/day deficit) to promote weight/fat loss. Meal tests were performed during the eucaloric phase for metabolic analyses. Dual-energy x-ray absorptiometry was used to evaluate body composition. RESULTS: Both groups experienced reductions in weight/adiposity, but the difference did not reach significance. The solid meal test indicated improved glucose/insulin homeostasis on the SPEC diet up to 3 hours postingestion. In addition, significantly lower triglycerides (P < 0.001) were observed on the SPEC diet. CONCLUSIONS: Dietary CHO reduction favorably influences metabolic parameters but did not result in greater weight/fat loss relative to a standard diet in obese AA girls. Future research is needed to determine long-term effectiveness of a reduced CHO diet on glucose and insulin homeostasis and how it may apply to weight maintenance/fat loss during development alone and/or in combination with additional weight loss/metabolic improvement strategies. PMID- 22067113 TI - TGF-beta2 induces maturation of immature human intestinal epithelial cells and inhibits inflammatory cytokine responses induced via the NF-kappaB pathway. AB - OBJECTIVES: Breast milk transforming growth factor (TGF)-beta2 is associated with healthy immune maturation and reduced risk of immune-mediated disease in infants. We sought to investigate whether conditioning with TGF-beta2 may result in a more mature immune responder phenotype in immature human intestinal epithelial cells (IECs). METHODS: Primary human fetal IECs (hFIECs) and the human fetal small intestinal epithelial cell line (H4 cells) were conditioned with breast milk levels of TGF-beta2, and an inflammatory response was subsequently induced. Inflammatory cytokine secretion and mRNA expression were measured by enzyme linked immunosorbent assay and quantitative real-time polymerase chain reaction, respectively. Alterations in activation of inflammatory signaling pathways were detected from IECs by immunoblotting and immunofluorescence. The effects of TGF beta2 conditioning on gene expression patterns in hFIECs were assessed by cDNA microarray analysis and quantitative PCR. RESULTS: Conditioning with TGF-beta2 significantly attenuated subsequent interleukin (IL)-1beta-, TNF-alpha-, and poly I:C-induced IL-8 and IL-6 responses in immature human IECs. Conditioning with TGF beta2 inhibited IL-1beta-induced IkappaB-alpha degradation and NF-kappaB p65 nuclear translocation, which may partially result from TGF-beta2-induced changes in the expression of genes in the NF-kappaB signaling pathway detected by cDNA microarray and qPCR. CONCLUSIONS: Conditioning with TGF-beta2 attenuates the subsequent inflammatory cytokine response in immature human IECs by inhibiting signaling in the NF-kappaB pathway. The immunomodulatory potential of breast milk may in part be mediated by TGF-beta2, which may provide a novel means of supporting intestinal immune maturation in neonates. PMID- 22067115 TI - Introduction to this special issue. Inmates and communicable and chronic diseases. PMID- 22067116 TI - A qualitative study of relationships among parenting strategies, social capital, the juvenile justice system, and mental health care for at-risk African American male youth. AB - For many poor, African American families living in the inner city, the juvenile justice system has become a de facto mental health service provider. In this article, longitudinal, ethnographic study methods were used to examine how resource-deprived, inner-city parents in a New York City community relied on the juvenile justice system to provide their African American male children with mental health care resources. The results of three case studies indicate that this strategy actually contributed to an escalation in delinquency among the youth. PMID- 22067117 TI - Challenges and strategies of frontline staff providing HIV services for inmates and releasees. AB - Linkages to services for HIV-infected inmates are critically important; however, little is known about the challenges faced by staff coordinating these linkages. This qualitative evaluation describes the challenges and strategies of frontline staff involved in HIV-related services for inmates and releasees participating in the Centers for Disease Control and Prevention/Health Resources and Services Administration Corrections Demonstration Project. Eight focus groups were held during a national meeting of community-based organizations. Content analysis revealed multiple themes. This evaluation emphasizes the lack of and difficulty obtaining services for this population. Staff recognize the role of security and safety when working in facilities and have identified methods to coordinate and communicate to facilitate their work. Communication with key partners and colleagues is important to understand the challenges and identify strategies; however, political advocacy is important for increased awareness and resources. Consideration of these issues within an ecological framework may help frontline staff translate findings to practice. PMID- 22067118 TI - Dihydrochalcone glycosides from Oxytropis myriophylla. AB - Chemical investigations of the 70% alcohol extract of Oxytropis myriophylla (Pall.) DC. (Leguminosae) have afforded the new natural product neohesperidin dihydrochalcone (1) and the known phloretin-4'-O-beta-D-glucopyranoside (2), which was the first reported from the genus Oxytropis. This paper reports the isolation and full spectroscopic characterization of compounds 1 and 2 by NMR, UV, IR and MS data. PMID- 22067127 TI - Expression of pro- and anti-angiogenic isoforms of VEGF in the mouse model of oxygen-induced retinopathy. AB - Retinopathy of prematurity (ROP) has become one of the leading causes of blindness and visual loss in children over the last half century. Vascular endothelial growth factor (VEGF-A) is the principal stimulator of angiogenesis. Recently, it has been identified that VEGF was differentially spliced from exons 8 to exons 8a and 8b to form two families: the pro-angiogenic VEGFxxx family and the anti-angiogenic VEGFxxxb family. This alternate splicing produced VEGFxxxb proteins of the same length as VEGFxxx family, but with different C terminal amino acid sequences. VEGFxxxb appeared to be able to inhibit VEGFxxx-dependent angiogenesis. In our study, we investigated the protein expression course of VEGFxxx and VEGFxxxb by Western-blot in a mouse model of Oxygen-induced Retinopathy (OIR) from postnatal day 1 (P1) to postnatal day 21 (P21). We also analyzed the relative protein expression level of VEGF(165)b isoform in the OIR mouse model. We found that both VEGFxxx and VEGFxxxb were present in the mouse retina, among which, VEGF(164) and VEGF(165)b appeared to be predominant VEGFxxx and VEGFxxxb isoforms respectively in the mouse retina. We also found that the two family had different expression pattern correlated with neovascularization development and that the relative expression level of VEGF(165)b isoform switched during the neovascularization development in the OIR mouse model. In OIR group, the protein level of total VEGF isoforms (a mix of VEGF(164) and VEGF(165)b, detected by pan-VEGF antibody) continuously increased and peaked at P17 while VEGF(165)b continuously decreased from P9 which was well related with the vessel obliteration and neovascularization development in the mouse model of OIR. The neovascularization development correlates with an increase of total VEGF isoforms and the decrease of VEGF(165)b, indicating that there is a pro-angiogenic VEGF shift. Therefore, anti-angiogenic therapy that could alter the ratio of VEGFxxxb/VEGFxxx may be more effective. PMID- 22067128 TI - Effect of prostaglandin analogues on tear proteomics and expression of cytokines and matrix metalloproteinases in the conjunctiva and cornea. AB - The purpose of this work was to identify potential tear-film-based proteins and their effect on changes in the conjunctiva and cornea in eyes using prostaglandin (PG) analogues. Recruited subjects were individuals who had used PG for at least 1 year and comparison with eyes of normal controls and timolol using patients were done. Approximately 3-5 MUL of tears were sampled from both eyes of each subject using glass microcapillaries. Proteomic analysis was done to compare the pooled tear samples from each group by Bradford assay and cytokine arrays. Impression cytology was used to gather mRNA from conjunctival epithelial cells, and target protein mRNA was quantified by PCR. Rabbits treated with PG were scarified, and changes in the corneal stroma were evaluated by immunohistochemical staining and western blot analysis. There were increased levels of IL-1beta, IL-6, MMP-1, MMP-3, and MMP-9 and decreased levels of TIMP-1 and TIMP-2 in the tears of PG-treated patients. The mRNA of IL-1beta, MMP-1, MMP 3, and MMP-9 was elevated and mRNA of TIMP-1 and TIMP-2 was decreased in the conjunctival epithelial cells. Rabbits treated with PG showed corneal thinning with decreased collagen type I expression. The protein of MMP-1 and MMP-9 was elevated and protein of TIMP-1 was decreased in the rabbit cornea by western blot analysis. Immunohistochemical staining showed elevated expression of MMP-1 and MMP-9 and the decreased expression of TIMP-1 in the corneal stroma. The topical use of PG analogues results in an altered balance between MMPs and TIMPs, which may be triggered by inflammatory cytokines. This results in an increase of matrix degradation and decrease of stromal collagens in the cornea by PG treatments. PMID- 22067129 TI - Removal of the basement membrane enhances corneal wound healing. AB - Recurrent corneal erosions are painful and put patients' vision at risk. Treatment typically begins with debridement of the area around the erosion site followed by more aggressive treatments. An in vivo mouse model has been developed that reproducibly induces recurrent epithelial erosions in wild-type mice spontaneously within two weeks after a single 1.5 mm corneal debridement wound created using a dulled-blade. This study was conducted to determine whether 1) inhibiting MMP9 function during healing after dulled-blade wounding impacts erosion development and 2) wounds made with a rotating-burr heal without erosions. Oral or topical inhibition of MMPs after dulled-blade wounding does not improve healing. Wounds made by rotating-burr heal with significantly fewer erosions than dulled-blade wounds. The localization of MMP9, beta4 integrin and basement membrane proteins (LN332 and type VII collagen), immune cell influx, and reinnervation of the corneal nerves were compared after both wound types. Rotating-burr wounds remove the anterior basement membrane centrally but not at the periphery near the wound margin, induce more apoptosis of corneal stromal cells, and damage more stromal nerve fibers. Despite the fact that rotating-burr wounds do more damage to the cornea, fewer immune cells are recruited and significantly more wounds resolve completely. PMID- 22067130 TI - Development of new therapeutic modalities for corneal endothelial disease focused on the proliferation of corneal endothelial cells using animal models. AB - This review describes our recent attempts to develop new therapeutic modalities for corneal endothelial disease using animal models including non-human primate model in which the proliferative ability of corneal endothelial cells is severely limited, as is the case in humans. First, we describe our attempt to develop new surgical treatments using cultivated corneal endothelial cells for advanced corneal endothelial dysfunction. It includes two different approaches; a "corneal endothelial cell sheet transplantation" with cells grown on a type-I collagen carrier, and a "cell-injection therapy" combined with the application of Rho kinase (ROCK) inhibitor. Recently, it was reported that the selective ROCK inhibitor, Y-27632, promotes cell adhesion and proliferation and inhibits the apoptosis of primate corneal endothelial cells in culture. When cultivated corneal endothelial cells were injected into the anterior chamber of animal eyes in the presence of ROCK inhibitor, endothelial cell adhesion was promoted and the cells achieved a high cell density and a morphology similar to corneal endothelial cells in vivo. We are also trying to develop a novel medical treatment for the early phase of corneal endothelial disease by the use of ROCK inhibitor eye drops. In rabbit and monkey experiments using partial endothelial dysfunction models, corneal endothelial wound healing was accelerated by the topical application of ROCK inhibitor to the ocular surface, and resulted in the regeneration of a corneal endothelial monolayer with a high endothelial cell density. We are now trying to advance the clinical application of these new therapies for patients with corneal endothelial dysfunction. PMID- 22067131 TI - Radical instability and spurious branch support by likelihood when applied to matrices with non-random distributions of missing data. AB - Non-random distributions of missing data are a general problem for likelihood based statistical analyses, including those in a phylogenetic context. Extensive non-randomly distributed missing data are particularly problematic in supermatrix analyses that include many terminals and/or loci. It has been widely reported that missing data can lead to loss of resolution, but only very rarely create misleading or otherwise unsupported results in a parsimony context. Yet this does not hold for all parametric-based analyses because of their assumption of homogeneity across characters and lineages, which can lead to both long-branch attraction and long-branch repulsion. Contrived examples were used to demonstrate that non-random distributions of missing data, even without rate heterogeneity among characters and a well fitting model, can provide misleading likelihood based topologies and branch-support values that are radically unstable based on slight modifications to character sampling. The same can occur despite complete absence of parsimony-informative characters. Otherwise unsupported resolution and high branch support for these clades were found to occur frequently in 22 empirical examples derived from a published supermatrix. Partitioning characters based on the distribution of missing data helped to decrease, but did not eliminate, these artifacts. These artifacts were exacerbated by low quality tree searches, particularly when holding only a single optimal tree that must be fully resolved. PMID- 22067132 TI - Evidence-based medicine comes to Gaza. PMID- 22067133 TI - The neurological manifestations of acute liver failure. AB - Acute liver failure is a disorder which impacts on multiple organ systems and results from hepatocellular necrosis in a patient with no previous history of chronic liver disease. It typically culminates in the development of liver dysfunction, coagulopathy and encephalopathy, and is associated with high mortality in poor prognostic groups. In acute liver failure, some patients may develop cerebral edema and increased intracranial pressure although recent data suggest that intracranial hypertension is less frequent than previously described, complicating 29% of acute cases who have proceeded to grade 3/4 coma. Neurological manifestations are primarily underpinned by the development of brain edema. The onset of encephalopathy can be rapid and dramatic with the development of asterixis, delirium, hyperreflexia, clonus, seizures, extensor posturing and coma. Ammonia plays a definitive role in the development of cytotoxic brain edema. Patients with acute liver failure have a marked propensity to develop renal insufficiency and hence impaired ammonia excretion. The incidence of both bacterial and fungal infection occurs in approximately one third of patients. The relationship between inflammation, as opposed to infection, and progression of encephalopathy is similar to that observed in chronic liver disease. Intracranial pressure monitoring is valuable in identifying surges in intracranial hypertension requiring intervention. Insertion of an intracranial bolt should be considered only in the subgroup of patients who have progressed to grade 4 coma. Risk factors for developing intracranial hypertension are those with hyperacute and acute etiologies, progression to grade 3/4 hepatic encephalopathy, those who develop pupillary abnormalities (dilated pupils, sluggishly responsive to light) or seizures, have systemic inflammation, an arterial ammonia >150 MUmol/L, hyponatremia, and those in receipt of vasopressor support. Strategies employed in patients with established encephalopathy (grade 3/4) aim to maintain freedom from infection/inflammatory milieu, provide adequate sedation, and correct hypo osmolality. PMID- 22067134 TI - Rat brain slices oxidize glucose at high rates: a (13)C NMR study. AB - Since glucose is the main cerebral substrate, we have characterized the metabolism of various (13)C glucose isotopomers in rat brain slices. For this, we have used our cellular metabolomic approach that combines enzymatic and carbon 13 NMR techniques with mathematical models of metabolic pathways. We identified the fate and the pathways of the conversion of glucose carbons into various products (pyruvate, lactate, alanine, aspartate, glutamate, GABA, glutamine and CO(2)) and determined absolute fluxes through pathways of glucose metabolism. After 60 min of incubation, lactate and CO(2) were the main end-products of the metabolism of glucose which was avidly metabolized by the slices. Lactate was also used at high rates by the slices and mainly converted into CO(2). High values of flux through pyruvate carboxylase, which were similar with glucose and lactate as substrate, were observed. The addition of glutamine, but not of acetate, stimulated pyruvate carboxylation, the conversion of glutamate into succinate and fluxes through succinate dehydrogenase, malic enzyme, glutamine synthetase and aspartate aminotransferase. It is concluded that, unlike brain cells in culture, and consistent with high fluxes through PDH and enzymes of the tricarboxylic acid cycle, rat brain slices oxidized both glucose and lactate at high rates. PMID- 22067135 TI - Selected sociodemographic factors and related differences in patterns of alcohol use among university students in Slovakia. AB - BACKGROUND: Alcohol use and misuse and their relation to sociodemograhic factors are well studied among university students in Western European countries and the USA, but less is known about students in Eastern Europe. The historical past as communistic countries might have affected the social life among these populations, which is again one of the main factors determining the alcohol consumption among university students. The aim of our study was to assess the association of selected sociodemographic factors with different patterns of alcohol use among university students in Slovakia. METHODS: A sample of 813 young adults (mean age 21.1 years, 63.8% females; response rate of 71%) from four universities in Kosice answered questions about their sociodemographic background and about alcohol use. To obtain a detailed picture of different aspects, alcohol use was measured by four variables: frequency of alcohol use, heavy episodic drinking, frequency of drunkenness and problem drinking. Four separate logistic regression models were used to assess the association between sociodemographic and alcohol-related variables. To assess the potentially different effects in both genders, all two-way interactions with gender were tested. RESULTS: While 41% of the students drank alcohol once a week or more often, 77% reported heavy episodic drinking and 49% had been drunk more than once in the last month. Problem drinking existed in 23.3% of the sample. Gender was consistently associated with all four alcohol-related variables, with males being at higher risk. A higher study year was associated only with lower levels of heavy episodic drinking, but displayed no association with the other studied variables. Living with parents during the semester was consistently associated with less frequent heavy episodic drinking, drunkenness episodes, and problem drinking while having an intimate relationship was associated with less problem drinking only. CONCLUSIONS: Our findings for the university students from Slovakia are in line with previous studies in Western Europe. Additionally, it appears that frequent alcohol use, excessive alcohol use (heavy episodic drinking and drunkenness) and problem drinking among university students represent a continuum and are influenced by the same sociodemographic factors. PMID- 22067136 TI - Spontaneous multiple cervical artery dissection in the puerperium. PMID- 22067137 TI - Long-term inhaled iloprost use in children with pulmonary arterial hypertension. AB - BACKGROUND: We performed a retrospective analysis of patients with pulmonary arterial hypertension receiving inhaled iloprost in a single centre to evaluate long-term tolerability, safety, and efficacy of chronic inhaled iloprost therapy in children. METHODS: A total of 20 patients with either idiopathic or associated pulmonary arterial hypertension were treated with iloprost between April, 2003 and January, 2010. The median age and weight of the patients were 3.8 years- ranging from 4 months to 19 years--and 12.3 kilograms--ranging from 4 to 73 kilograms-- respectively. Pulmonary arterial hypertension was idiopathic or hereditary in eight patients (40%) and associated with congenital cardiac disease in 12 patients (60%). RESULTS: Of the 20 patients, 15 had combined therapy--12 patients with two and three patients with three different classes of drugs. In all, six patients died during follow-up. The median follow-up time was 18 months, ranging from 6 to 74 months. The 6-minute walking test was performed in 7 out of 20 patients at baseline and on follow-up. The median 6-minute walking test increased from 420 to 490 metres after iloprost therapy (p = 0.028). After initiation of iloprost therapy, one patient complained of headache and another had a rash around his mouth, none necessitating discontinuation of therapy. Overall compliance with inhaled iloprost was good. CONCLUSION: Pulmonary hypertension is associated with significant morbidity and mortality. Careful assessment of each patient and timely combination of specific vasodilator therapy is needed to improve clinical outcomes. This study suggests that inhaled iloprost, with or without concomitant endotelin receptor antagonist and/or phosphodiesterase inhibitor, is safe and efficacious for treatment of pulmonary arterial hypertension in children. PMID- 22067138 TI - Nutritional determinants of cognitive aging and dementia. AB - The objective of this review is to provide an overview of nutritional factors involved in cognitive aging and dementia with a focus on nutrients that are also important in neurocognitive development. Several dietary components were targeted, including antioxidant nutrients, dietary fats and B-vitamins. A critical review of the literature on each nutrient group is presented, beginning with laboratory and animal studies of the underlying biological mechanisms, followed by prospective epidemiological studies and randomised clinical trials. The evidence to date is fairly strong for protective associations of vitamin E from food sources, the n-3 fatty acid, DHA, found in fish, a high ratio of polyunsaturated to saturated fats, and vitamin B12 and folate. Attention to the level of nutrient intake is crucial for interpreting the literature and the inconsistencies across studies. Most of the epidemiological studies that observe associations have sufficient numbers of individuals who have both low and adequate nutrient status. Few of the randomised clinical trials are designed to target participants who have low baseline status before randomising to vitamin supplement treatments, and this may have resulted in negative findings. Post-hoc analyses by some of the trials reveal vitamin effects in individuals with low baseline intakes. The field of diet and dementia is a relatively young area of study. Much further work needs to be done to understand dietary determinants of cognitive aging and diseases. Further, these studies must be particularly focused on the levels of nutrient intake or status that confer optimum or suboptimal brain functioning. PMID- 22067139 TI - Parkinson's disease and dementia: a longitudinal study (DEMPARK). AB - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative motor disorder. However, non-motor complications frequently alter the course of the disease. A particularly disabling non-motor symptom is dementia. METHODS/DESIGN: The study is designed as a multicentre prospective, observational cohort study of about 700 PD patients aged 45-80 years with or without dementia and PD-mild cognitive impairment (MCI). The patients will be recruited in eight specialized movement disorder clinics and will be followed for 36 months. Information about the patients' functional status will be assessed at baseline and 6-/12- month intervals. In addition, 120 patients with dementia with Lewy bodies (DLB) will be included. Well-established standardized questionnaires/tests will be applied for detailed neuropsychological assessment. In addition, patients will be asked to participate in modules including volumetric MRI, genetic parameters, and neuropsychology to detect risk factors, early diagnostic biomarkers and predictors for dementia in PD. RESULTS: The study included 604 PD patients by March 2011; 56.3% were classified as having PD alone, with 30.6% of patients suffering from PD-MCI and 13.1% from PD with dementia. The mean age of the cohort was 68.6 +/- 7.9 years, with a mean disease duration of 6.8 +/- 5.4 years. There was a preponderance of patients in the earlier Hoehn and Yahr stages. CONCLUSION: The main aim of the study is to characterize the natural progression of cognitive impairment in PD and to identify factors which contribute to the evolution and/or progression of the cognitive impairment. To accomplish this aim we established a large cohort of PD patients without cognitive dysfunction, PD patients with MCI, and PD patients with dementia, to characterize these patients in a standardized manner, using imaging (serial structural MRI), genetic and proteomic methods in order to improve our understanding of the course of the PD process and the development of cognitive dysfunction and dementia in this disease. The inclusion of the DLB patients will start in the second quarter of 2011 in the BMBF-funded follow-up project LANDSCAPE. PMID- 22067140 TI - Combining brain diagnosis and therapy in a single strategy: the safety, reliability, and cost implications using same-day versus separate-day stereotactic procedures. AB - BACKGROUND: A therapeutic radiosurgery procedure usually follows a separate diagnostic stereotactic procedure after days or weeks. OBJECTIVES: To define the clinical reliability, safety, and cost implications of same-day diagnostic stereotactic biopsy and therapeutic radiosurgery. METHODS: During an 8-year interval, 26 patients underwent stereotactic brain biopsy followed by immediate therapeutic stereotactic radiosurgery in a single-day combined procedure. The intraoperative diagnosis was determined using standard histopathological techniques. Diagnostic accuracy, hospital costs, and contribution margins associated with this treatment strategy were compared to those of 26 case-matched patients (controls) who underwent a stereotactic diagnostic procedure followed by a separate-day outpatient SRS procedure within 6 weeks during the same time interval. RESULTS: The intraoperative diagnosis correlated with the final histopathological diagnosis in 96% of the patients. Biopsy-related morbidity did not occur in this series. The mean total costs of same-day patients was significantly lower than the costs of patients who had two-stage procedures (USD 9,077 +/- 2,366 vs. 11,284 +/- 3,025; p = 0.008). The net contribution to the hospital margin of USD 13,736 was not significantly different between the two management strategies. CONCLUSIONS: The advantages of the same-day approach included a single stereotactic head frame application, reduced total admission time, consecutive histopathological diagnosis and therapy in a single hospital admission, and reduced total hospital costs. For patients who are highly suspected to have a brain tumor for which SRS is likely to be an effective therapeutic strategy, same-day diagnostic stereotactic biopsy followed by therapeutic SRS proved to be a safe, reliable, and cost-effective management strategy. PMID- 22067142 TI - Analyzing 2D gel images using a two-component empirical Bayes model. AB - BACKGROUND: Two-dimensional polyacrylomide gel electrophoresis (2D gel, 2D PAGE, 2-DE) is a powerful tool for analyzing the proteome of a organism. Differential analysis of 2D gel images aims at finding proteins that change under different conditions, which leads to large-scale hypothesis testing as in microarray data analysis. Two-component empirical Bayes (EB) models have been widely discussed for large-scale hypothesis testing and applied in the context of genomic data. They have not been implemented for the differential analysis of 2D gel data. In the literature, the mixture and null densities of the test statistics are estimated separately. The estimation of the mixture density does not take into account assumptions about the null density. Thus, there is no guarantee that the estimated null component will be no greater than the mixture density as it should be. RESULTS: We present an implementation of a two-component EB model for the analysis of 2D gel images. In contrast to the published estimation method, we propose to estimate the mixture and null densities simultaneously using a constrained estimation approach, which relies on an iteratively re-weighted least squares algorithm. The assumption about the null density is naturally taken into account in the estimation of the mixture density. This strategy is illustrated using a set of 2D gel images from a factorial experiment. The proposed approach is validated using a set of simulated gels. CONCLUSIONS: The two-component EB model is a very useful for large-scale hypothesis testing. In proteomic analysis, the theoretical null density is often not appropriate. We demonstrate how to implement a two-component EB model for analyzing a set of 2D gel images. We show that it is necessary to estimate the mixture density and empirical null component simultaneously. The proposed constrained estimation method always yields valid estimates and more stable results. The proposed estimation approach proposed can be applied to other contexts where large-scale hypothesis testing occurs. PMID- 22067141 TI - Human brain endothelial cells endeavor to immunoregulate CD8 T cells via PD-1 ligand expression in multiple sclerosis. AB - BACKGROUND: Multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), is characterized by blood-brain barrier (BBB) disruption and massive infiltration of activated immune cells. Engagement of programmed cell death-1 (PD-1) expressed on activated T cells with its ligands (PD-L1 and PD-L2) suppresses T cell responses. We recently demonstrated in MS lesions elevated PD L1 expression by glial cells and absence of PD-1 on many infiltrating CD8 T cells. We have now investigated whether human brain endothelial cells (HBECs), which maintain the BBB, can express PD-L1 or PD-L2 and thereby modulate T cells. METHODS: We used primary cultures of HBECs isolated from non-tumoral CNS tissue either under basal or inflamed conditions. We assessed the expression of PD-L1 and PD-L2 using qPCR and flow cytometry. Human CD8 T cells were isolated from peripheral blood of healthy donors and co-cultured with HBECs. Following co culture with HBECs, proliferation and cytokine production by human CD8 T cells were measured by flow cytometry whereas transmigration was determined using a well established in vitro model of the BBB. The functional impact of PD-L1 and PD L2 provided by HBECs was determined using blocking antibodies. We performed immunohistochemistry for the detection of PD-L1 or PD-L2 concurrently with caveolin-1 (a cell specific marker for endothelial cells) on post-mortem human brain tissues obtained from MS patients and normal controls. RESULTS: Under basal culture conditions, PD-L2 is expressed on HBECs, whilst PD-L1 is not detected. Both ligands are up-regulated under inflammatory conditions. Blocking PD-L1 and PD-L2 leads to increased transmigration and enhanced responses by human CD8 T cells in co-culture assays. Similarly, PD-L1 and PD-L2 blockade significantly increases CD4 T cell transmigration. Brain endothelium in normal tissues and MS lesions does not express detectable PD-L1; in contrast, all blood vessels in normal brain tissues are PD-L2-positive, while only about 50% express PD-L2 in MS lesions. CONCLUSIONS: Our observations suggest that brain endothelial cells contribute to control T cell transmigration into the CNS and immune responses via PD-L2 expression. However, such impact is impaired in MS lesions due to downregulation of endothelium PD-L2 levels. PMID- 22067143 TI - Detection of coronary stenosis with myocardial contrast echocardiography using regadenoson, a selective adenosine A2A receptor agonist. AB - AIMS: Regadenoson is comparable to adenosine in pharmacologic radionuclide stress tests but has not been studied with stress myocardial contrast echocardiography. This study assessed the haemodynamic profile and ability of regadenoson, a novel selective A(2A) receptor agonist, to detect coronary artery stenosis during myocardial contrast echocardiography. METHODS AND RESULTS: Myocardial contrast echocardiography was performed to measure myocardial blood volume, myocardial blood flow velocity, and total regional myocardial blood flow before and after administration of regadenoson (5 ug kg(-1), 10 s bolus) in 10 open-chest dogs with mild-to-moderate coronary stenosis that was not flow limiting at rest. Regadenoson decreased blood pressure but did not change heart rate. It increased coronary blood flow significantly (P < 0.05) for 30 min, which was attenuated in proportion to coronary stenosis severity. Whereas myocardial blood volume maximally increased by 0.5-0.75-fold in the control region, it did not change in the region supplied by the non-flow limiting stenosis. Perfusion defects were visually and quantitatively detectable for as long as 10 min after administration of regadenoson. No arrhythmias were noted with regadenoson either prior to or during myocardial contrast echocardiography. CONCLUSION: Regadenoson can be used as a vasodilator stress agent with myocardial contrast echocardiography to detect the presence of physiologically significant coronary stenosis. The optimum time for image acquisition was 3-10 min after drug administration. PMID- 22067144 TI - Characterization of Mg2+ inhibition of mitochondrial Ca2+ uptake by a mechanistic model of mitochondrial Ca2+ uniporter. AB - Ca(2+) is an important regulatory ion and alteration of mitochondrial Ca(2+) homeostasis can lead to cellular dysfunction and apoptosis. Ca(2+) is transported into respiring mitochondria via the Ca(2+) uniporter, which is known to be inhibited by Mg(2+). This uniporter-mediated mitochondrial Ca(2+) transport is also shown to be influenced by inorganic phosphate (Pi). Despite a large number of experimental studies, the kinetic mechanisms associated with the Mg(2+) inhibition and Pi regulation of the uniporter function are not well established. To gain a quantitative understanding of the effects of Mg(2+) and Pi on the uniporter function, we developed here a mathematical model based on known kinetic properties of the uniporter and presumed Mg(2+) inhibition and Pi regulation mechanisms. The model is extended from our previous model of the uniporter that is based on a multistate catalytic binding and interconversion mechanism and Eyring's free energy barrier theory for interconversion. The model satisfactorily describes a wide variety of experimental data sets on the kinetics of mitochondrial Ca(2+) uptake. The model also appropriately depicts the inhibitory effect of Mg(2+) on the uniporter function, in which Ca(2+) uptake is hyperbolic in the absence of Mg(2+) and sigmoid in the presence of Mg(2+). The model suggests a mixed-type inhibition mechanism for Mg(2+) inhibition of the uniporter function. This model is critical for building mechanistic models of mitochondrial bioenergetics and Ca(2+) handling to understand the mechanisms by which Ca(2+) mediates signaling pathways and modulates energy metabolism. PMID- 22067145 TI - Qualitative network modeling of the Myc-p53 control system of cell proliferation and differentiation. AB - A kinetic model of a molecular control system for the cellular decision to proliferate or differentiate is formulated and analyzed for the purpose of understanding how the system can break down in cancer cells. The proposed core of this control system is composed of the transcription factors Myc and p53. The network of interactions between these factors involves negative and positive feedback loops that are linked to pathways involved in differentiation, cell cycle, and apoptosis. Understanding the dynamics of the Myc-p53 control system is aided by the postulate that there exists a cancer zone defined as a range of oncogenic Myc activities where the probability of initiating cancer is high. We propose that an essential role of p53 is to prevent the system from entering or staying too long in the cancer zone by downregulating Myc or, when Myc activity somehow becomes too high, by inducing apoptosis, cell cycle arrest, or differentiation. Kinetic modeling illustrates how deletions or aberrations in PTEN, MDM2, and ARF (genes implicated in various cancers, including glioma) affect the Myc-p53 control system. In addition, computer simulations demonstrate how this control system generates different cellular phenotypes characterized by rates of cellular differentiation and proliferation. PMID- 22067146 TI - Quantitative modeling of membrane deformations by multihelical membrane proteins: application to G-protein coupled receptors. AB - The interpretation of experimental observations of the dependence of membrane protein function on the properties of the lipid membrane environment calls for a consideration of the energy cost of protein-bilayer interactions, including the protein-bilayer hydrophobic mismatch. We present a novel (to our knowledge) multiscale computational approach for quantifying the hydrophobic mismatch-driven remodeling of membrane bilayers by multihelical membrane proteins. The method accounts for both the membrane remodeling energy and the energy contribution from any partial (incomplete) alleviation of the hydrophobic mismatch by membrane remodeling. Overcoming previous limitations, it allows for radially asymmetric bilayer deformations produced by multihelical proteins, and takes into account the irregular membrane-protein boundaries. The approach is illustrated by application to two G-protein coupled receptors: rhodopsin in bilayers of different thickness, and the serotonin 5-HT(2A) receptor bound to pharmacologically different ligands. Analysis of the results identifies the residual exposure that is not alleviated by bilayer adaptation, and its quantification at specific transmembrane segments is shown to predict favorable contact interfaces in oligomeric arrays. In addition, our results suggest how distinct ligand-induced conformations of G-protein coupled receptors may elicit different functional responses through differential effects on the membrane environment. PMID- 22067147 TI - Linking flickering to waves and whole-cell oscillations in a mitochondrial network model. AB - It has been shown that transient single mitochondrial depolarizations, known as flickers, tend to occur randomly in space and time. On the other hand, many studies have shown that mitochondrial depolarization waves and whole-cell oscillations occur under oxidative stress. How single mitochondrial flickering events and whole-cell oscillations are mechanistically linked remains unclear. In this study, we developed a Markov model of the inner membrane anion channel in which reactive-oxidative-species (ROS)-induced opening of the inner membrane anion channel causes transient mitochondrial depolarizations in a single mitochondrion that occur in a nonperiodic manner, simulating flickering. We then coupled the individual mitochondria into a network, in which flickers occur randomly and sparsely when a small number of mitochondria are in the state of high superoxide production. As the number of mitochondria in the high-superoxide production state increases, short-lived or abortive waves due to ROS-induced ROS release coexist with flickers. When the number of mitochondria in the high superoxide-production state reaches a critical number, recurring propagating waves are observed. The origins of the waves occur randomly in space and are self organized as a consequence of random flickering and local synchronization. We show that at this critical state, the depolarization clusters exhibit a power-law distribution, a signature of self-organized criticality. In addition, the whole cell mitochondrial membrane potential changes from exhibiting small random fluctuations to more periodic oscillations as the superoxide production rate increases. These simulation results may provide mechanistic insight into the transition from random mitochondrial flickering to the waves and whole-cell oscillations observed in many experimental studies. PMID- 22067148 TI - Permeabilized rat cardiomyocyte response demonstrates intracellular origin of diffusion obstacles. AB - Intracellular diffusion restrictions for ADP and other molecules have been predicted earlier based on experiments on permeabilized fibers or cardiomyocytes. However, it is possible that the effective diffusion distance is larger than the cell dimensions due to clumping of cells and incomplete separation of cells in fiber preparations. The aim of this work was to check whether diffusion restrictions exist inside rat cardiomyocytes or are caused by large effective diffusion distance. For that, we determined the response of oxidative phosphorylation (OxPhos) to exogenous ADP and ATP stimulation in permeabilized rat cardiomyocytes using fluorescence microscopy. The state of OxPhos was monitored via NADH and flavoprotein autofluorescence. By varying the ADP or ATP concentration in flow chamber, we determined that OxPhos has a low affinity in cardiomyocytes. The experiments were repeated in a fluorometer on cardiomyocyte suspensions leading to similar autofluorescence changes induced by ADP as recorded under the microscope. ATP stimulated OxPhos more in a fluorometer than under the microscope, which was attributed to accumulation of ADP in fluorometer chamber. By calculating the flow profile around the cell in the microscope chamber and comparing model solutions to measured data, we demonstrate that intracellular structures impose significant diffusion obstacles in rat cardiomyocytes. PMID- 22067149 TI - Investigating circular dorsal ruffles through varying substrate stiffness and mathematical modeling. AB - Circular dorsal ruffles (CDRs) are transient actin-rich ringlike structures that form on the dorsal surface of growth-factor stimulated cells. However, the dynamics and mechanism of formation of CDRs are still unknown. It has been observed that CDR formation leads to stress fibers disappearing near the CDRs. Because stress fiber formation can be modified by substrate stiffness, we examined the effect of substrate stiffness on CDR formation by seeding NIH 3T3 fibroblasts on glass and polydimethylsiloxane substrates of varying stiffnesses from 20 kPa to 1800 kPa. We found that increasing substrate stiffness increased the lifetime of the CDRs. We developed a mathematical model of the signaling pathways involved in CDR formation to provide insight into this lifetime and size dependence that is linked to substrate stiffness via Rac-Rho antagonism. From the model, increasing stiffness raised mDia1-nucleated stress fiber formation due to Rho activation. The increased stress fibers present increased replenishment of the G-actin pool, therefore prolonging Arp2/3-nucleated CDR formation due to Rac activation. Negative feedback by WAVE-related RacGAP on Rac explained how CDR actin propagates as an excitable wave, much like wave propagation in other excitable medium, e.g., nerve signal transmission. PMID- 22067150 TI - Focal adhesion kinase stabilizes the cytoskeleton. AB - Focal adhesion kinase (FAK) is a central focal adhesion protein that promotes focal adhesion turnover, but the role of FAK for cell mechanical stability is unknown. We measured the mechanical properties of wild-type (FAKwt), FAK deficient (FAK-/-), FAK-silenced (siFAK), and siControl mouse embryonic fibroblasts by magnetic tweezer, atomic force microscopy, traction microscopy, and nanoscale particle tracking microrheology. FAK-deficient cells showed lower cell stiffness, reduced adhesion strength, and increased cytoskeletal dynamics compared to wild-type cells. These observations imply a reduced stability of the cytoskeleton in FAK-deficient cells. We attribute the reduced cytoskeletal stability to rho-kinase activation in FAK-deficient cells that suppresses the formation of ordered stress fiber bundles, enhances cortical actin distribution, and reduces cell spreading. In agreement with this interpretation is that cell stiffness and cytoskeletal stability in FAK-/- cells is partially restored to wild-type level after rho-kinase inhibition with Y27632. PMID- 22067151 TI - Topographic modulation of the orientation and shape of cell nuclei and their influence on the measured elastic modulus of epithelial cells. AB - The influence of nucleus shape and orientation on the elastic modulus of epithelial cells was investigated with atomic force microscopy. The shape and orientation were controlled by presenting the epithelial cells with anisotropic parallel ridges and grooves of varying pitch at the cell substratum. As the cells oriented to the underlying topography, the volume of the nucleus increased as the pitch of the topography increased from 400 nm to 2000 nm. The increase in nucleus volume was reflected by an increase in the measured elastic modulus of the topographically aligned cells. Significant alterations in the shape of the nucleus, by intimate contact with the topographic ridge and grooves of the underlying cell, were also observed via confocal microscopy, indicating that the nucleus may also act as a direct mechanosensor of substratum topography. PMID- 22067152 TI - Extracellular proton modulation of the cardiac voltage-gated sodium channel, Nav1.5. AB - Low pH depolarizes the voltage dependence of voltage-gated sodium (Na(V)) channel activation and fast inactivation. A complete description of Na(V) channel proton modulation, however, has not been reported. The majority of Na(V) channel proton modulation studies have been completed in intact tissue. Additionally, several Na(V) channel isoforms are expressed in cardiac tissue. Characterizing the proton modulation of the cardiac Na(V) channel, Na(V)1.5, will thus help define its contribution to ischemic arrhythmogenesis, where extracellular pH drops from pH 7.4 to as low as pH 6.0 within ~10 min of its onset. We expressed the human variant of Na(V)1.5 with and without the modulating beta(1) subunit in Xenopus oocytes. Lowering extracellular pH from 7.4 to 6.0 affected a range of biophysical gating properties heretofore unreported. Specifically, acidic pH destabilized the fast-inactivated and slow-inactivated states, and elevated persistent I(Na). These data were incorporated into a ventricular action potential model that displayed a reduced maximum rate of depolarization as well as disparate increases in epicardial, mid-myocardial, and endocardial action potential durations, indicative of an increased heterogeneity of repolarization. Portions of these data were previously reported in abstract form. PMID- 22067153 TI - Role of the KcsA channel cytoplasmic domain in pH-dependent gating. AB - The KcsA channel is a representative potassium channel that is activated by changes in pH. Previous studies suggested that the region that senses pH is entirely within its transmembrane segments. However, we recently revealed that the cytoplasmic domain also has an important role, because its conformation was observed to change dramatically in response to pH changes. Here, to investigate the effects of the cytoplasmic domain on pH-dependent gating, we made a chimera mutant channel consisting of the cytoplasmic domain of the KcsA channel and the transmembrane region of the MthK channel. The chimera showed a pH dependency similar to that of KcsA, indicating that the cytoplasmic domain can act as a pH sensor. To identify how this region detects pH, we substituted certain cytoplasmic domain amino acids that are normally negatively charged at pH 7 for neutral ones in the KcsA channels. These mutants opened independently of pH, suggesting that electrostatic charges have a major role in the cytoplasmic domain's ability to sense and respond to pH. PMID- 22067154 TI - Bax forms two types of channels, one of which is voltage-gated. AB - When activated, the proapoptotic protein Bax permeabilizes the mitochondrial outer membrane, allowing the release of proteins into the cytosol and thus initiating the execution phase of apoptosis. When activated Bax was reconstituted into phospholipid membranes, we discovered a new, to our knowledge, property of Bax channels: voltage gating. We also found that the same Bax sample under the same experimental conditions could give rise to two radically different channels: Type A, which is small, well behaved, homogeneous, and voltage-gated, and Type B, which is large, noisy, and voltage-independent. One Type B channel can be converted irreversibly into a population of Type A channels by the addition of La(3+). This conversion process appears to involve a two-dimensional budding mechanism. The existence of these two types of Bax channels suggests a process for controlling the degree of mitochondrial outer membrane permeabilization. PMID- 22067156 TI - Divalent cation-dependent formation of electrostatic PIP2 clusters in lipid monolayers. AB - Polyphosphoinositides are among the most highly charged molecules in the cell membrane, and the most common polyphosphoinositide, phosphatidylinositol-4,5 bisphosphate (PIP(2)), is involved in many mechanical and biochemical processes in the cell membrane. Divalent cations such as calcium can cause clustering of the polyanionic PIP(2), but the origin and strength of the effective attractions leading to clustering has been unclear. In addition, the question of whether the ion-mediated attractions could be strong enough to alter the mechanical properties of the membrane, to our knowledge, has not been addressed. We study phase separation in mixed monolayers of neutral and highly negatively charged lipids, induced by the addition of divalent positively charged counterions, both experimentally and numerically. We find good agreement between experiments on mixtures of PIP(2) and 1-stearoyl-2-oleoyl phosphatidylcholine and simulations of a simplified model in which only the essential electrostatic interactions are retained. In addition, we find numerically that under certain conditions the effective attractions can rigidify the resulting clusters. Our results support an interpretation of PIP(2) clustering as governed primarily by electrostatic interactions. At physiological pH, the simulations suggest that the effective attractions are strong enough to give nearly pure clusters of PIP(2) even at small overall concentrations of PIP(2). PMID- 22067155 TI - FRET detection of calmodulin binding to the cardiac RyR2 calcium release channel. AB - Calmodulin (CaM) binding to the type 2 ryanodine receptor (RyR2) regulates Ca release from the cardiac sarcoplasmic reticulum (SR). However, the structural basis of CaM regulation of the RyR2 is poorly defined, and the presence of other potential CaM binding partners in cardiac myocytes complicates resolution of CaM's regulatory interactions with RyR2. Here, we show that a fluorescence resonance-energy-transfer (FRET)-based approach can effectively resolve RyR2 CaM binding, both in isolated SR membrane vesicles and in permeabilized ventricular myocytes. A small FRET donor was targeted to the RyR2 cytoplasmic assembly via fluorescent labeling of the FKBP12.6 subunit. Acceptor fluorophore was attached at discrete positions within either the N- or the C-lobe of CaM. FRET between FKBP12.6 and CaM bound to SR vesicles indicated CaM binding at a single high affinity site within 60 A of FKBP12.6. Micromolar Ca increased the apparent affinity of CaM binding and slowed CaM dissociation, but did not significantly affect maximal FRET efficiency at saturating CaM. FRET was strongest when the acceptor was attached at either of two positions within CaM's N-lobe versus sites in CaM's C-lobe, providing CaM orientation information. In permeabilized ventricular myocytes, FKBP12.6 and CaM colocalized to Z-lines, and the efficiency of energy transfer to both the N- and C-lobes of CaM was comparable to that observed in SR vesicle experiments. Results also indicate that both the location and orientation of CaM binding on the RyR2 are very similar to the skeletal muscle RyR1 isoform. Specific binding of CaM to functional RyR2 channels in the cardiac myocyte environment can be monitored using FKBP biosensors and FRET. PMID- 22067157 TI - Crystal structure of a phosphorylated light chain domain of scallop smooth-muscle myosin. AB - We have determined the crystal structure of a phosphorylated smooth-muscle myosin light chain domain (LCD). This reconstituted LCD is of a sea scallop catch muscle myosin with its phosphorylatable regulatory light chain (RLC SmoA). In the crystal structure, Arg(16), an arginine residue that is present in this isoform but not in vertebrate smooth-muscle RLC, stabilizes the phosphorylation site. This arginine interacts with the carbonyl group of the phosphorylation-site serine in the unphosphorylated LCD (determined previously), and with the phosphate group when the serine is phosphorylated. However, the overall conformation of the LCD is essentially unchanged upon phosphorylation. This result provides additional evidence that phosphorylation of the RLC is unlikely to act as an on-switch in regulation of scallop catch muscle myosin. PMID- 22067158 TI - Crowding of molecular motors determines microtubule depolymerization. AB - The assembly and disassembly dynamics of microtubules (MTs) is tightly controlled by MT-associated proteins. Here, we investigate how plus-end-directed depolymerases of the kinesin-8 family regulate MT depolymerization dynamics. Using an individual-based model, we reproduce experimental findings. Moreover, crowding is identified as the key regulatory mechanism of depolymerization dynamics. Our analysis reveals two qualitatively distinct regimes. For motor densities above a particular threshold, a macroscopic traffic jam emerges at the plus-end and the MT dynamics become independent of the motor concentration. Below this threshold, microscopic traffic jams at the tip arise that cancel out the effect of the depolymerization kinetics such that the depolymerization speed is solely determined by the motor density. Because this density changes over the MT length, length-dependent regulation is possible. Remarkably, motor cooperativity affects only the end-residence time of depolymerases and not the depolymerization speed. PMID- 22067159 TI - A change in the radius of rotation of F1-ATPase indicates a tilting motion of the central shaft. AB - F(1)-ATPase is a water-soluble portion of F(o)F(1)-ATP synthase and rotary molecular motor that exhibits reversibility in chemical reactions. The rotational motion of the shaft subunit gamma has been carefully scrutinized in previous studies, but a tilting motion of the shaft has never been explicitly postulated. Here we found a change in the radius of rotation of the probe attached to the shaft subunit gamma between two different intermediate states in ATP hydrolysis: one waiting for ATP binding, and the other waiting for ATP hydrolysis and/or subsequent product release. Analysis of this radial difference indicates a ~4 degrees outward tilting of the gamma-subunit induced by ATP binding. The tilt angle is a new parameter, to our knowledge, representing the motion of the gamma subunit and provides a new constraint condition of the ATP-waiting conformation of F(1)-ATPase, which has not been determined as an atomic structure from x-ray crystallography. PMID- 22067160 TI - Calcium and stretch activation modulate power generation in Drosophila flight muscle. AB - Many animals regulate power generation for locomotion by varying the number of muscle fibers used for movement. However, insects with asynchronous flight muscles may regulate the power required for flight by varying the calcium concentration ([Ca(2+)]). In vivo myoplasmic calcium levels in Drosophila flight muscle have been found to vary twofold during flight and to correlate with aerodynamic power generation and wing beat frequency. This mechanism can only be possible if [Ca(2+)] also modulates the flight muscle power output and muscle kinetics to match the aerodynamic requirements. We found that the in vitro power produced by skinned Drosophila asynchronous flight muscle fibers increased with increasing [Ca(2+)]. Positive muscle power generation started at pCa = 5.8 and reached its maximum at pCa = 5.25. A twofold variation in [Ca(2+)] over the steepest portion of this curve resulted in a two- to threefold variation in power generation and a 1.2-fold variation in speed, matching the aerodynamic requirements. To determine the mechanism behind the variation in power, we analyzed the tension response to muscle fiber-lengthening steps at varying levels of [Ca(2+)]. Both calcium-activated and stretch-activated tensions increased with increasing [Ca(2+)]. However, calcium tension saturated at slightly lower [Ca(2+)] than stretch-activated tension, such that as [Ca(2+)] increased from pCa = 5.7 to pCa = 5.4 (the range likely used during flight), stretch- and calcium activated tension contributed 80% and 20%, respectively, to the total tension increase. This suggests that the response of stretch activation to [Ca(2+)] is the main mechanism by which power is varied during flight. PMID- 22067161 TI - Characterizing and controlling the motion of ssDNA in a solid-state nanopore. AB - Sequencing DNA in a synthetic solid-state nanopore is potentially a low-cost and high-throughput method. Essential to the nanopore-based DNA sequencing method is the ability to control the motion of a single-stranded DNA (ssDNA) molecule at single-base resolution. Experimental studies showed that the average translocation speed of DNA driven by a biasing electric field can be affected by ionic concentration, solvent viscosity, or temperature. Even though it is possible to slow down the average translocation speed, instantaneous motion of DNA is too diffusive to allow each DNA base to stay in front of a sensor site for its measurement. Using extensive all-atom molecular dynamics simulations, we study the diffusion constant, friction coefficient, electrophoretic mobility, and effective charge of ssDNA in a solid-state nanopore. Simulation results show that the spatial fluctuation of ssDNA in 1 ns is comparable to the spacing between neighboring nucleotides in ssDNA, which makes the sensing of a DNA base very difficult. We demonstrate that the recently proposed DNA transistor could potentially solve this problem by electrically trapping ssDNA inside the DNA transistor and ratcheting ssDNA base-by-base in a biasing electric field. When increasing the biasing electric field, we observed that the translocation of ssDNA changes from ratcheting to steady-sliding. The simulated translocation of ssDNA in the DNA transistor was theoretically characterized using Fokker-Planck analysis. PMID- 22067162 TI - Base-flipping mechanism in postmismatch recognition by MutS. AB - DNA mismatch recognition and repair is vital for preserving the fidelity of the genome. Conserved across prokaryotes and eukaryotes, MutS is the primary protein that is responsible for recognizing a variety of DNA mismatches. From molecular dynamics simulations of the Escherichia coli MutS-DNA complex, we describe significant conformational dynamics in the DNA surrounding a G.T mismatch that involves weakening of the basepair hydrogen bonding in the basepair adjacent to the mismatch and, in one simulation, complete base opening via the major groove. The energetics of base flipping was further examined with Hamiltonian replica exchange free energy calculations revealing a stable flipped-out state with an initial barrier of ~2 kcal/mol. Furthermore, we observe changes in the local DNA structure as well as in the MutS structure that appear to be correlated with base flipping. Our results suggest a role of base flipping as part of the repair initiation mechanism most likely leading to sliding-clamp formation. PMID- 22067163 TI - Size distribution of amyloid nanofibrils. AB - We consider the size distribution of amyloid nanofibrils (protofilaments) in nucleating protein solutions when the nucleation process occurs by the mechanism of direct polymerization of beta-strands (extended peptides or protein segments) into beta-sheets. Employing the atomistic nucleation theory, we derive a general expression for the stationary size distribution of amyloid nanofibrils constituted of successively layered beta-sheets. The application of this expression to amyloid beta(1-40) (Abeta(40)) fibrils allows us to determine the nanofibril size distribution as a function of the protein concentration and temperature. The distribution is most remarkable with its exhibiting a series of peaks positioned at "magic" nanofibril sizes (or lengths), which are due to deep local minima in the work for fibril formation. This finding of magic sizes or lengths is consistent with experimental results for the size distribution of aggregates in solutions of Abeta(40) proteins. Also, our approach makes it possible to gain insight into the effect of point mutations on the nanofibril size distribution, an effect that may play a role in experimentally observed substantial differences in the fibrillation lag-time of wild-type and point mutated amyloid-beta proteins. PMID- 22067165 TI - Smoothing protein energy landscapes by integrating folding models with structure prediction. AB - Decades of work has investigated the energy landscapes of simple protein models, but what do the landscapes of real, large, atomically detailed proteins look like? We explore an approach to this problem that systematically extracts simple funnel models of actual proteins using ensembles of structure predictions and physics-based atomic force fields and sampling. Central to our effort are calculations of a quantity called the relative entropy, which quantifies the extent to which a given set of structure decoys and a putative native structure can be projected onto a theoretical funnel description. We examine 86 structure prediction targets and one coupled folding-binding system, and find that in a majority of cases the relative entropy robustly signals which structures are nearest to native (i.e., which appear to lie closest to a funnel bottom). Importantly, the landscape model improves substantially upon purely energetic measures in scoring decoys. Our results suggest that physics-based models including both folding theories and all-atom force fields-may be successfully integrated with structure prediction efforts. Conversely, detailed predictions of structures and the relative entropy approach enable one to extract coarse topographic features of protein landscapes that may enhance the development and application of simpler folding models. PMID- 22067164 TI - Segmental polymorphism in a functional amyloid. AB - Although amyloid fibrils are generally considered to be causative or contributing agents in amyloid diseases, several amyloid fibrils are also believed to have biological functions. Among these are fibrils formed by Pmel17 within melanosomes, which act as a template for melanin deposition. We use solid-state NMR to show that the molecular structures of fibrils formed by the 130-residue pseudo-repeat domain Pmel17:RPT are polymorphic even within the biologically relevant pH range. Thus, biological function in amyloid fibrils does not necessarily imply a unique molecular structure. Solid-state NMR spectra of three Pmel17:RPT polymorphs show that in all cases, only a subset (~30%) of the full amino acid sequence contributes to the immobilized fibril core. Although the repetitive nature of the sequence and incomplete spectral resolution prevent the determination of unique chemical shift assignments from two- and three dimensional solid-state NMR spectra, we use a Monte Carlo assignment algorithm to identify protein segments that are present in or absent from the fibril core. The results show that the identity of the core-forming segments varies from one polymorph to another, a phenomenon known as segmental polymorphism. PMID- 22067166 TI - Distinct hydration properties of wild-type and familial point mutant A53T of alpha-synuclein associated with Parkinson's disease. AB - The propensity of alpha-synuclein to form amyloid plays an important role in Parkinson's disease. Three familial mutations, A30P, E46K, and A53T, correlate with Parkinson's disease. Therefore, unraveling the structural effects of these mutations has basic implications in understanding the molecular basis of the disease. Here, we address this issue through comparing details of the hydration of wild-type alpha-synuclein and its A53T mutant by a combination of wide-line NMR, differential scanning calorimetry, and molecular dynamics simulations. All three approaches suggest a hydrate shell compatible with a largely disordered state of both proteins. Its fine details, however, are different, with the mutant displaying a somewhat higher level of hydration, suggesting a bias to more open structures, favorable for protein-protein interactions leading to amyloid formation. These differences disappear in the amyloid state, suggesting basically the same surface topology, irrespective of the initial monomeric state. PMID- 22067167 TI - Carbon nanotube inhibits the formation of beta-sheet-rich oligomers of the Alzheimer's amyloid-beta(16-22) peptide. AB - Alzheimer's disease is associated with the abnormal self-assembly of the amyloid beta (Abeta) peptide into toxic beta-rich aggregates. Experimental studies have shown that hydrophobic nanoparticles retard Abeta fibrillation by slowing down the nucleation process; however, the effects of nanoparticles on Abeta oligomeric structures remain elusive. In this study, we investigate the conformations of Abeta(16-22) octamers in the absence and presence of a single-walled carbon nanotube (SWCNT) by performing extensive all-atom replica exchange molecular dynamics simulations in explicit solvent. Our simulations starting from eight random chains demonstrate that the addition of SWCNT into Abeta(16-22) solution prevents beta-sheet formation. Simulation starting from a prefibrillar beta-sheet octamer shows that SWCNT destabilizes the beta-sheet structure. A detailed analysis of the Abeta(16-22)/SWCNT/water interactions reveals that both the inhibition of beta-sheet formation and the destabilization of prefibrillar beta sheets by SWCNT result from the same physical forces: hydrophobic and pi-stacking interactions (with the latter playing a more important role). By analyzing the stacking patterns between the Phe aromatic rings and the SWCNT carbon rings, we find that short ring-centroid distances mostly favor parallel orientation, whereas large distances allow all other orientations to be populated. Overall, our computational study provides evidence that SWCNT is likely to inhibit Abeta(16-22) and full-length Abeta fibrillation. PMID- 22067168 TI - Analysis of aquaporin-mediated diffusional water permeability by coherent anti stokes Raman scattering microscopy. AB - Water can pass through biological membranes via two pathways: simple diffusion through the lipid bilayer, or water-selective facilitated diffusion through aquaporins (AQPs). Although AQPs play an important role in osmotic water permeability (P(f)), the role of AQPs in diffusional water permeability remains unclear because of the difficulty of measuring diffusional water permeability (P(d)). Here, we report an accurate and instantaneous method for measuring the P(d) of a single HeLa S3 cell using coherent anti-Stokes Raman scattering (CARS) microscopy with a quick perfusion device for H(2)O/D(2)O exchange. Ultra-high speed line-scan CARS images were obtained every 0.488 ms. The average decay time constant of CARS intensities (tau(CARS)) for the external solution H(2)O/D(2)O exchange was 16.1 ms, whereas the intracellular H(2)O/D(2)O exchange was 100.7 +/ 19.6 ms. To evaluate the roles of AQP in diffusional water permeability, AQP4 fused with enhanced green fluorescent protein (AQP4-EGFP) was transiently expressed in HeLa S3 cells. The average tau(CARS) for the intracellular H(2)O/D(2)O exchange in the AQP4-EGFP-HeLa S3 cells was 43.1 +/- 15.8 ms. We also assessed the cell volume and the cell surface area to calculate P(d). The average P(d) values for the AQP4-EGFP-HeLa S3 cells and the control EGFP-HeLa S3 cells were 2.7 +/- 1.0 * 10(-3) and 8.3 +/- 2.6 * 10(-4) cm/s, respectively. AQP4 mediated water diffusion was independent of the temperature but was dependent on the expression level of the protein at the plasma membrane. These results suggest the possibility of using CARS imaging to investigate the hydrodynamics of single mammalian cells as well as the regulation of AQPs. PMID- 22067169 TI - Quantification of fluorophore copy number from intrinsic fluctuations during fluorescence photobleaching. AB - We present a theoretical technique for quantifying the cellular copy-number of fluorophores that relies on the random nature of the photobleaching process. Our approach does not require single-molecule sensitivity, and therefore can be used with commonly used epifluorescence microscopes. Fluctuations arising from photobleaching can be used to estimate the proportionality between fluorescence intensity and copy-number, which can then be used with subsequent intensity measurements to estimate copy-number. We calculate the statistical errors of our approach and verify them with stochastic simulations. By using fluctuations over the entire photobleaching process, we obtain significantly smaller errors than previous approaches that have used fluctuations arising from cytoplasmic proteins partitioning during cellular division. From the time-dependence of the fluctuations as photobleaching proceeds, we can discriminate between desired photobleach fluctuations and background noise or photon shot noise. Our approach does not require cellular division and the photobleaching rate sets a timescale that is adjustable with respect to cellular processes. We hope that our approach will now be applied experimentally. PMID- 22067170 TI - DNA multiphoton absorption generates localized damage for studying repair dynamics in live cells. AB - Investigations into the spatiotemporal dynamics of DNA repair using live-cell imaging are aided by the ability to generate well defined regions of ultravioletlike photolesions in an optical microscope. We demonstrate that multiphoton excitation of DNA in live cells with visible femtosecond pulses produces thymine cyclopyrimidine dimers (CPDs), the primary ultraviolet DNA photoproduct. The CPDs are produced with a cubic to supercubic power dependence using pulses in the wavelength range from at least 400 to 525 nm. We show that the CPDs are confined in all three spatial dimensions, making multiphoton excitation of DNA with visible light an ideal technique for generating localized DNA photolesions in a wide variety of samples, from cultured cells to thicker tissues. We demonstrate the utility of this method by applying it to investigate the spatiotemporal recruitment of GFP-tagged topoisomerase I (TopI) to sites of localized DNA damage in polytene chromosomes within live cells of optically thick Drosophila salivary glands. PMID- 22067171 TI - Poroelasticity of cartilage at the nanoscale. AB - Atomic-force-microscopy-based oscillatory loading was used in conjunction with finite element modeling to quantify and predict the frequency-dependent mechanical properties of the superficial zone of young bovine articular cartilage at deformation amplitudes, delta, of ~15 nm; i.e., at macromolecular length scales. Using a spherical probe tip (R ~ 12.5 MUm), the magnitude of the dynamic complex indentation modulus, |E*|, and phase angle, phi, between the force and tip displacement sinusoids, were measured in the frequency range f ~ 0.2-130 Hz at an offset indentation depth of delta(0) ~ 3 MUm. The experimentally measured |E*| and phi corresponded well with that predicted by a fibril-reinforced poroelastic model over a three-decade frequency range. The peak frequency of phase angle, f(peak), was observed to scale linearly with the inverse square of the contact distance between probe tip and cartilage, 1/d(2), as predicted by linear poroelasticity theory. The dynamic mechanical properties were observed to be independent of the deformation amplitude in the range delta = 7-50 nm. Hence, these results suggest that poroelasticity was the dominant mechanism underlying the frequency-dependent mechanical behavior observed at these nanoscale deformations. These findings enable ongoing investigations of the nanoscale progression of matrix pathology in tissue-level disease. PMID- 22067172 TI - Operative approach and venous thromboembolism in colorectal surgery: casual or causal association? PMID- 22067173 TI - Practice parameters for the management of perianal abscess and fistula-in-ano. PMID- 22067174 TI - Readmission rates and cost following colorectal surgery. AB - BACKGROUND: Hospital readmission is emerging as a quality indicator by the state, federal, and private payors with the goal of denying payment for select readmissions. OBJECTIVE: We designed a study to measure the rate, cost, and risk factors for hospital readmission after colorectal surgery. STUDY DESIGN/SETTING: We reviewed commercial health insurance records of 10,882 patients who underwent colorectal surgery over a 7-year period (2002-2008). PATIENTS: All patients undergoing colon and/or rectal resection ages 18 to 64 were included. MAIN OUTCOME MEASURE: The 30-day and 90-day readmission rates, the number of readmissions per patient, the median cost, length of stay, and risk factors for readmission were analyzed. RESULTS: Thirty-day readmission occurred in 11.4% (1239/10,882) of patients. Readmission between 31 and 90 days occurred in an additional 11.9% (1027/10,882) of patients for a total 90-day readmission rate of 23.3%. Two or more readmissions occurred in 1.4% (155) and 5.2% (570) of patients in the first 30 and 90 days. Mean readmission length of stay was 8 days, and the median cost per stay was $8885. Initial hospitalization risk factors for readmission were the diagnosis of a surgical site infection (OR 1.2), creation of a stoma (OR 1.2), discharge to nursing home (OR 1.2), index admission length of stay >7 days (OR 1.2), proctectomy (OR 1.1), and severity of illness score (severity of illness 3 = OR 1.1; severity of illness 4 = OR 1.3). CONCLUSIONS: Readmission after colorectal surgery occurs frequently and is associated with a cost of approximately $9000 per readmission. Nationwide these findings account for $300 million in readmission costs annually for colorectal surgery alone. Clinical and systems-based prevention strategies are needed to reduce readmission. PMID- 22067175 TI - Preoperative diagnosis of Lynch syndrome with DNA mismatch repair immunohistochemistry on a diagnostic biopsy. AB - BACKGROUND: DNA mismatch repair immunohistochemistry on tumor tissue is a simple, readily available, and cost-effective method of identifying patients with Lynch syndrome in the postoperative setting. The aim of the study was to assess whether the mismatch repair status of a colorectal cancer can be confirmed by mismatch repair immunohistochemistry on preoperative biopsy. DESIGN: Germline positive patients with Lynch syndrome were identified from a prospectively collected Familial Cancer Clinic database. Preoperative colorectal cancer biopsy specimens were obtained from the source pathology provider to generate a cohort of matched preoperative and postoperative specimens. The specimens were sectioned and stained for 4 mismatch repair proteins (MLH1, MSH2, MSH6, PMS2). An age-matched cohort to compare specimens was selected from Bethesda positive but mismatch repair immunohistochemistry negative patients. All slides were reviewed by a single blinded pathologist. The Wilson method was used to calculate a true underlying proportion of patients for whom the preoperative result matched the postoperative test result with a 95% confidence interval. RESULTS: Of 128 germline positive mutation carriers, 40 patients (mean age 41, SD 11.3) had colorectal resections. Thirty-three preoperative specimens were retrievable and were matched with biopsies from 33 controls. The germline mutations included in the study were 8 MLH1, 19 MSH2, 3 MSH6, and 2 PMS2. In patients where germline positive status was known, sensitivity was 100% (95% CI 89.2-100) and specificity was 100% (95% CI 89.2-100). Identical sensitivity and specificity were observed in 33 age-matched patients. The sensitivity of the endoscopic biopsy in predicting germline status was 94.9% (95% CI 80.4-98.3). CONCLUSION: The mismatch repair disease status of a colorectal cancer can be reliably confirmed by mismatch repair immunohistochemistry on a diagnostic colorectal cancer biopsy sample before definitive surgery. Ascertaining a diagnosis of Lynch syndrome before definitive surgery can influence surgical planning.